PMID- 18801919
TI  - The measurement of plasma aldosterone in patients post-myocardial infarction.

PMID- 18801920
TI  - Synergy between gemifloxacin and trimethoprim/sulfamethoxazole against community
      associated methicillin-resistant Staphylococcus aureus.
AB  - OBJECTIVES: The rapid emergence of methicillin-resistant Staphylococcus aureus
      from the community (CA-MRSA) presents difficulties in making treatment choices.
      We evaluated whether combining another orally available agent commonly used to
      treat CA-MRSA with gemifloxacin would enhance gemifloxacin activity against CA
      MRSA. METHODS: Fifty strains of SCCmec IV, agr group 1, Panton-Valentine
      leucocidin-positive CA-MRSA were evaluated for susceptibilities to gemifloxacin,
      trimethoprim/sulfamethoxazole, doxycycline, levofloxacin, rifampicin, clindamycin
      and erythromycin. Twenty of these strains were evaluated for the potential for
      synergy between gemifloxacin and trimethoprim/sulfamethoxazole, clindamycin and
      rifampicin by time-kill analysis. Two strains were further evaluated in an in
      vitro pharmacokinetic/pharmacodynamic (PK/PD) model. RESULTS: In time-kill
      analyses, gemifloxacin combined with trimethoprim/sulfamethoxazole produced
      additivity (6/20) or synergy (11/20) in 85% of the isolates tested. The addition
      of clindamycin to gemifloxacin showed additivity (3/20) or synergy (2/20) in 25%
      of the isolates. All isolates displayed indifference to the combination of
      gemifloxacin and rifampicin. In the PK/PD model, combining gemifloxacin and
      trimethoprim/sulfamethoxazole provided potent and sustained bactericidal activity
      to detection limits of 2 log(10) cfu/mL by 48 h; gemifloxacin combined with
      clindamycin or with rifampicin killed to detection limits by 56 h or later. One
      isolate developed efflux-mediated resistance to gemifloxacin at 96 h with
      gemifloxacin monotherapy. All combinations prevented the emergence of this
      resistance. CONCLUSIONS: Synergy or additivity was demonstrated by time-kill
      analysis between gemifloxacin and trimethoprim/sulfamethoxazole in most isolates
      tested. In the PK/PD model, the addition of trimethoprim/sulfamethoxazole,
      clindamycin and rifampicin enhanced the activity of gemifloxacin against CA-MRSA
      and suppressed the emergence of resistance to gemifloxacin.

PMID- 18801921
TI  - Global warming: stop worrying, start panicking?

PMID- 18801923
TI  - Flt1, pregnancy, and malaria: evolution of a complex interaction.

PMID- 18801922
TI  - Rapid enhancement of two-step wiring plasticity by estrogen and NMDA receptor
      activity.
AB  - Cortical information storage requires combined changes in connectivity and
      synaptic strength between neurons, but the signaling mechanisms underlying this
      two-step wiring plasticity are unknown. Because acute 17beta-estradiol (E2)
      modulates cortical memory, we examined its effects on spine morphogenesis, AMPA
      receptor trafficking, and GTPase signaling in cortical neurons. Acute E2
      application resulted in a rapid, transient increase in spine density, accompanied
      by temporary formation of silent synapses through reduced surface GluR1. These
      rapid effects of E2 were dependent on a Rap/AF-6/ERK1/2 pathway. Intriguingly,
      NMDA receptor (NMDAR) activation after E2 treatment potentiated silent synapses
      and elevated spine density for as long as 24 h. Hence, we show that E2
      transiently increases neuronal connectivity by inducing dynamic nascent spines
      that "sample" the surrounding neuropil and that subsequent NMDAR activity is
      sufficient to stabilize or "hold" E2-mediated effects. This work describes a form
      of two-step wiring plasticity relevant for cortical memory and identifies targets
      that may facilitate recovery from brain injuries.

PMID- 18801924
TI  - Caveolin-1 regulates the secretion and cytoprotection of Cyr61 in hyperoxic cell
      death.
AB  - Cysteine-rich 61 (Cyr61) belongs to the CCN family and mediates cell
      proliferation, survival, and apoptosis. Our previous studies showed that Cyr61
      protected against hyperoxia-induced lung cell death via Akt phosphorylation.
      Caveolin-1 (cav-1), a 22-kDa transmembrane scaffolding protein, is the principal
      structural component of caveolae. Emerging data show that cav-1 regulates signal
      transduction-associated proteins that reside in the caveolae. Numerous integrin
      related pathways, including PI3K/Akt-induced cell survival are controlled by cav
      1-mediated signaling. Our data showed that recombinant Cyr61 promoted cell
      proliferation and resistance to hyperoxia-induced cell death in vitro.
      Neutralizing antibodies reversed the above effects, indicating functional role of
      secreted Cyr61 in response to hyperoxic stress. While deletion of cav-1 protected
      cells from hyperoxia-induced cell death, Cyr61-neutralizing antibodies abolished
      this protective effect. Furthermore, Cyr61 and cav-1 colocalized and physically
      interacted via integrins in bronchial epithelial cells. Deletion of cav-1
      increased extracellular and decreased cytosolic Cyr61, both in vitro and in vivo.
      Pretreatment with Brefeldin A increased intracellular Cyr61 in cav-1(-/-) cells,
      while decreasing extracellular Cyr61. Taken together, Cav-1/Cyr61 interaction via
      integrins represents a novel pathway of Cyr61 signaling involving cav-1-dependent
      processes, which play a critical role in regulating hyperoxia-induced cell death.

PMID- 18801925
TI  - Different regulation of eosinophil activity in Crohn's disease compared with
      ulcerative colitis.
AB  - The aim of this investigation was to study the involvement of eosinophil and
      neutrophil granulocytes in different stages of Crohn's disease (CD) and
      ulcerative colitis (UC). Biopsy samples were taken from the right flexure of the
      colon and from the rectum in patients with active (n=12) and inactive colonic CD
      (n=7), patients with active (n=33) and inactive UC (n=24), and from control
      subjects (n=11). Cell suspensions from biopsies and blood were analyzed by flow
      cytometry with regards to activation markers and viability. Immunohistochemistry
      was used to evaluate cell number and degranulation. Blood eosinophils were
      cultured with Th1 and Th2 cytokines, and the expression of activity markers was
      assessed by flow cytometry. Eosinophil number, viability, and activity were
      increased during active CD and UC compared with controls. The activity, assessed
      as CD44 expression, tended to diminish during inactive CD but was increased
      further in quiescent UC. Neutrophil number and activity were increased only
      during inflammation in both diseases. Culture of blood eosinophils with IL-5 and
      IL-13 caused increased CD44 expression, whereas IL-5 and IFN-gamma induced
      elevated CD69 expression. We observed different patterns of eosinophil activation
      in CD and UC, with the highest CD44 expression during quiescent UC. Our in vitro
      experiments with recombinant cytokines suggest that the diverse mechanisms of
      eosinophil activation in CD and UC are a result of different cytokine milieus
      (Th1 vs. Th2). In contrast, neutrophil activation reflects the disease activity
      in CD and UC, irrespective of Th cell skewing.

PMID- 18801926
TI  - A panel study in congestive heart failure to estimate the short-term effects from
      personal factors and environmental conditions on oxygen saturation and pulse
      rate.
AB  - OBJECTIVES: Recent studies suggest that persons with congestive heart failure
      (CHF) may be at higher risk for short-term effects of air pollution. This daily
      diary panel study in Montreal, Quebec, was carried out to determine whether
      oxygen saturation and pulse rate were associated with selected personal factors,
      weather conditions and air pollution. METHODS: Thirty-one subjects with CHF
      participated in this study in 2002 and 2003. Over a 2-month period, the
      investigators measured their oxygen saturation, pulse rate, weight and
      temperature each morning and recorded these and other data in a daily diary. Air
      pollution and weather conditions were obtained from fixed-site monitoring
      stations. The study made use of mixed regression models, adjusting for within
      subject serial correlation and temporal trends, to determine the association
      between oxygen saturation and pulse rate and personal and environmental
      variables. Depending on the model, we accounted for the effects of a variety of
      personal variables (eg, body temperature, salt consumption) as well as nitrogen
      dioxide (NO2), ozone, maximum temperature and change in barometric pressure at
      8:00 from the previous day. RESULTS: In multivariable analyses, the study found
      that oxygen saturation was reduced when subjects reported that they were ill,
      consumed salt, or drank liquids on the previous day and had higher body
      temperatures on the concurrent day (only the latter was statistically
      significant). Relative humidity and decreased atmospheric pressure from the
      previous day were associated with oxygen saturation. In univariate analyses,
      there was negative associations with concentrations of fine particulates, ozone,
      and sulphur dioxide (SO2), but only SO2 was significant after adjustment for the
      effects of weather. For pulse rate, no associations were found for the personal
      variables and in univariate analyses the study found positive associations with
      NO(2), fine particulates (aerodynamic diameter of 2.5 microm or under, PM(2.5)),
      SO2, and maximum temperature, although only the latter two were significant after
      adjustment for environmental effects. CONCLUSIONS: The findings from the present
      investigation suggest that personal and environmental conditions affect
      intermediate physiological parameters that may affect the health of CHF patients.

PMID- 18801927
TI  - Volcanic sulfur dioxide and acute respiratory symptoms on Miyakejima island.
AB  - OBJECTIVES: Following a volcanic eruption in 2000, high concentrations of ambient
      sulfur dioxide (SO2) are still observed on Miyakejima, Japan despite the reversal
      2 years ago of the ban on residents living on the island. This study examines the
      association between current levels of volcanic SO2 and the incidence of acute
      subjective symptoms in volunteers on Miyakejima. METHODS: The authors conducted a
      follow-up study on 611 healthy volunteers, on a person-hour basis (28 413 person
      hours), who visited the island to provide support to residents from February to
      July 2005. Adverse health symptoms were measured by self-administered diary and
      exposure was approximated using monitoring data across 14 sites. Associations
      between incidence rates and increasing SO2 levels (reference (the lowest), very
      low, low, middle and high) were examined using Poisson regression. RESULTS:
      Hourly incidence of cough, scratchy throat, sore throat and breathlessness showed
      clear exposure-response relationships with SO2 concentrations. There were
      statistically significant risks of those symptoms at relatively low SO2 levels.
      Thus, rate ratios in the 0.6-2.0 ppm exposure band (vs <0.01 ppm) were: for
      cough, 3.4 (95% CI 1.8 to 6.6) in men and 9.8 (3.9 to 24.9) in women; for sore
      throat, 3.2 (1.7 to 6.2) in men and 5.8 (2.0 to 16.5) in women; and for
      breathlessness, 10.5 (4.2 to 26.6) in men and 18.5 (4.6 to 74.3) in women. Little
      evidence of SO2 effects on sputum and nasal discharge/congestion was observed in
      this study. Eye and skin irritations showed inconsistent results between hourly
      maximal and hourly mean SO2 concentrations. CONCLUSION: The authors observed
      strong evidence of an exposure-response relationship between volcanic SO2 and
      subjective acute respiratory symptoms among a healthy population on Miyakejima.
      The results are consistent with reports that females and non-smokers are more
      sensitive to irritant gas than males and smokers, respectively.

PMID- 18801928
TI  - Respiratory and skin hypersensitivity reactions caused by a peptide coupling
      reagent.

PMID- 18801929
TI  - Insulin-like growth factor I receptor signaling is required for exercise-induced
      cardiac hypertrophy.
AB  - The receptors for IGF-I (IGF-IR) and insulin (IR) have been implicated in
      physiological cardiac growth, but it is unknown whether IGF-IR or IR signaling
      are critically required. We generated mice with cardiomyocyte-specific knockout
      of IGF-IR (CIGF1RKO) and compared them with cardiomyocyte-specific insulin
      receptor knockout (CIRKO) mice in response to 5 wk exercise swim training.
      Cardiac development was normal in CIGF1RKO mice, but the hypertrophic response to
      exercise was prevented. In contrast, despite reduced baseline heart size, the
      hypertrophic response of CIRKO hearts to exercise was preserved. Exercise
      increased IGF-IR content in control and CIRKO hearts. Akt phosphorylation
      increased in exercise-trained control and CIRKO hearts and, surprisingly, in
      CIGF1RKO hearts as well. In exercise-trained control and CIRKO mice, expression
      of peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC
      1alpha) and glycogen content were both increased but were unchanged in trained
      CIGF1RKO mice. Activation of AMP-activated protein kinase (AMPK) and its
      downstream target eukaryotic elongation factor-2 was increased in exercise
      trained CIGF1RKO but not in CIRKO or control hearts. In cultured neonatal rat
      cardiomyocytes, activation of AMPK with 5-aminoimidazole-4-carboxamide-1-beta-D
      ribofuranoside (AICAR) prevented IGF-I/insulin-induced cardiomyocyte hypertrophy.
      These studies identify an essential role for IGF-IR in mediating physiological
      cardiomyocyte hypertrophy. IGF-IR deficiency promotes energetic stress in
      response to exercise, thereby activating AMPK, which leads to phosphorylation of
      eukaryotic elongation factor-2. These signaling events antagonize Akt signaling,
      which although necessary for mediating physiological cardiac hypertrophy, is
      insufficient to promote cardiac hypertrophy in the absence of myocardial IGF-I
      signaling.

PMID- 18801930
TI  - Steroidal androgens and nonsteroidal, tissue-selective androgen receptor
      modulator, S-22, regulate androgen receptor function through distinct genomic and
      nongenomic signaling pathways.
AB  - Androgen receptor (AR) ligands are important for the development and function of
      several tissues and organs. However, the poor oral bioavailability,
      pharmacokinetic properties, and receptor cross-reactivity of testosterone,
      coupled with side effects, place limits on its clinical use. Selective AR
      modulators (SARMs) elicit anabolic effects in muscle and bone, sparing
      reproductive organs like the prostate. However, molecular mechanisms underlying
      the tissue selectivity remain ambiguous. We performed a variety of in vitro
      studies to compare and define the molecular mechanisms of an aryl propionamide
      SARM, S-22, as compared with dihydrotestosterone (DHT). Studies indicated that S
      22 increased levator ani muscle weight but decreased the size of prostate in
      rats. Analysis of the upstream intracellular signaling events indicated that S-22
      and DHT mediated their actions through distinct pathways. Modulation of these
      pathways altered the recruitment of AR and its cofactors to the PSA enhancer in a
      ligand-dependent fashion. In addition, S-22 induced Xenopus laevis oocyte
      maturation and rapid phosphorylation of several kinases, through pathways
      distinct from steroids. These studies reveal novel differences in the molecular
      mechanisms by which S-22, a nonsteroidal SARM, and DHT mediate their
      pharmacological effects.

PMID- 18801931
TI  - A crucial role for Galphaq/11, but not Galphai/o or Galphas, in gonadotropin
      releasing hormone receptor-mediated cell growth inhibition.
AB  - GnRH acts on its cognate receptor in pituitary gonadotropes to regulate the
      biosynthesis and secretion of gonadotropins. It may also have direct
      extrapituitary actions, including inhibition of cell growth in reproductive
      malignancies, in which GnRH activation of the MAPK cascades is thought to play a
      pivotal role. In extrapituitary tissues, GnRH receptor signaling has been
      postulated to involve coupling of the receptor to different G proteins. We
      examined the ability of the GnRH receptor to couple directly to Galpha(q/11),
      Galpha(i/o), and Galpha(s), their roles in the activation of the MAPK cascades,
      and the subsequent cellular effects. We show that in Galpha(q/11)-negative cells
      stably expressing the GnRH receptor, GnRH did not induce activation of ERK, jun-N
      terminal kinase, or P38 MAPK. In contrast to Galpha(i) or chimeric Galpha(qi5),
      transfection of Galpha(q) cDNA enabled GnRH to induce phosphorylation of ERK, jun
      N-terminal kinase, and P38. Furthermore, no GnRH-mediated cAMP response or
      inhibition of isoproterenol-induced cAMP accumulation was observed. In another
      cellular background, [35S]GTPgammaS binding assays confirmed that the GnRH
      receptor was unable to directly couple to Galpha(i) but could directly interact
      with Galpha(q/11). Interestingly, GnRH stimulated a marked reduction in cell
      growth only in cells expressing Galpha(q), and this inhibition could be
      significantly rescued by blocking ERK activation. We therefore provide direct
      evidence, in multiple cellular backgrounds, that coupling of the GnRH receptor to
      Galpha(q/11), but not to Galpha(i/o) or Galpha(s), and consequent activation of
      ERK plays a crucial role in GnRH-mediated cell death.

PMID- 18801932
TI  - Regulation of glucose transporter 4 translocation by the Rab guanosine
      triphosphatase-activating protein AS160/TBC1D4: role of phosphorylation and
      membrane association.
AB  - Insulin-stimulated translocation of the glucose transporter GLUT4 to the plasma
      membrane in muscle and fat cells depends on the phosphatidylinositide 3
      kinase/Akt pathway. The downstream target AS160/TBC1D4 is phosphorylated upon
      insulin stimulation and contains a TBC domain (Tre-2/Bub2/Cdc16) that is present
      in most Rab guanosine triphosphatase-activating proteins. TBC1D4 associates with
      GLUT4-containing membranes under basal conditions and dissociates from membranes
      with insulin. Here we show that the association of TBC1D4 with membranes is
      required for its inhibitory action on GLUT4 translocation under basal conditions.
      Whereas the insulin-dependent dissociation of TBC1D4 from membranes was not
      required for GLUT4 translocation, its phosphorylation was essential. Many
      agonists that stimulate GLUT4 translocation failed to trigger TBC1D4
      translocation to the cytosol, but in most cases these agonists stimulated TBC1D4
      phosphorylation at T642, and their effects on GLUT4 translocation were inhibited
      by overexpression of the TBC1D4 phosphorylation mutant (TBC1D4-4P). We postulate
      that TBC1D4 acts to impede GLUT4 translocation by disarming a Rab protein found
      on GLUT4-containing-membranes and that phosphorylation of TBC1D4 per se is
      sufficient to overcome this effect, allowing GLUT4 translocation to the cell
      surface to proceed.

PMID- 18801933
TI  - Tissue- and context-dependent modulation of hormonal sensitivity of
      glucocorticoid-responsive genes by hexamethylene bisacetamide-inducible protein
      1.
AB  - Physiological and pharmacological processes mediated by glucocorticoids involve
      tissue- and context-specific regulation of glucocorticoid-responsive gene
      expression via glucocorticoid receptor (GR). However, the molecular mechanisms
      underlying such highly coordinated regulation of glucocorticoid actions remain to
      be studied. We here addressed this issue using atp1a1 and scnn1a, both of which
      are up-regulated in response to corticosteroids in human embryonic kidney-derived
      293 cells, but resistant in liver-derived HepG2 cells. Hexamethylene bisacetamide
      inducible protein 1 (HEXIM1) represses gene expression via, at least, two
      distinct mechanisms, i.e. positive transcription elongation factor b
      sequestration and direct interaction with GR, and is relatively high in HepG2
      cells compared with 293 cells. Given this, we focused on the role of HEXIM1 in
      transcriptional regulation of these GR target genes. In HepG2 cells, hormone
      resistance of atp1a1 and scnn1a was diminished by either knockdown of HEXIM1 or
      overexpression of GR. Such a positive effect of exogenous expression of GR was
      counteracted by concomitant overexpression of HEXIM1, indicating the balance
      between GR and HEXIM1 modulates hormonal sensitivity of these genes. In support
      of this, the hormone-dependent recruitment of RNA polymerase II onto atp1a1
      promoter was in parallel with that of GR. Moreover, we revealed that not positive
      transcription elongation factor b-suppressing activity but direct interaction
      with GR of HEXIM1 plays a major role in suppression of promoter recruitment of
      the receptor and subsequent atp1a1 and scnn1a gene activation. Collectively, we
      may conclude that HEXIM1 may participate in tissue-selective determination of
      glucocorticoid sensitivity via direct interaction with GR at least in certain
      gene sets including atp1a1 and scnn1a.

PMID- 18801934
TI  - A personalized approach to cancer treatment: how biomarkers can help.
AB  - BACKGROUND: The present approach to cancer treatment is often referred to as
      "trial and error" or "one size fits all." This practice is inefficient and
      frequently results in inappropriate therapy and treatment-related toxicity. In
      contrast, personalized treatment has the potential to increase efficacy and
      decrease toxicity. CONTENT: We reviewed the literature relevant to prognostic,
      predictive, and toxicity-related markers in cancer, with particular attention to
      systematic reviews, prospective randomized trials, and guidelines issued by
      expert panels. To achieve personalized treatment for cancer, we need markers for
      determining prognosis, predicting response to therapy, and predicting severe
      toxicity related to treatment. Among the best-validated prognostic markers
      currently available are serum concentrations of alpha-fetoprotein (AFP), human
      chorionic gonadotropin (hCG), and lactate dehydrogenase (LDH) for patients with
      nonseminoma germ cell tumors and tissue concentrations of both urokinase
      plasminogen activator and plasminogen activator inhibitor 1 (PAI-1) for breast
      cancer patients. Clinically useful therapy predictive markers are estrogen and
      progesterone receptors to select patients with breast cancer for treatment with
      endocrine therapy and human epidermal growth factor receptor 2 (HER-2) to select
      breast cancer patients for treatment with trastuzumab (Herceptin). Markers
      available for identifying drug-induced adverse reactions include thiopurine
      methyltransferase (TPMT) to predict toxicity from thiopurines in the treatment of
      acute lymphoblastic leukemia and uridine diphosphate glucuronyltransferase to
      predict toxicity from irinotecan in the treatment of colorectal cancer.
      CONCLUSIONS: Validated prognostic, predictive, and toxicity markers should help
      cancer treatment move from the current trial-and-error approach to more
      personalized treatment.

PMID- 18801935
TI  - Quantification of thyroglobulin, a low-abundance serum protein, by immunoaffinity
      peptide enrichment and tandem mass spectrometry.
AB  - BACKGROUND: Quantification of serum tumor markers plays an important role in
      determining whether patients treated for cancer require further therapy. Whereas
      large-scale proteomic efforts aim to identify novel tumor markers to facilitate
      early detection, optimization of methods for quantifying known tumor markers
      offers another approach to improving management of malignancies. For example,
      immunoassays used in clinical practice to measure established tumor markers
      suffer from potential interference from endogenous immunoglobulins and imperfect
      concordance across platforms-problems that also plague many other immunoassays.
      To address these important limitations, this study used peptide immunoaffinity
      enrichment in concert with liquid chromatography-tandem mass spectrometry (LC
      MS/MS) to quantify thyroglobulin, a well-characterized tumor marker. METHODS: We
      identified 3 peptides in tryptic digests of thyroglobulin that were detected at
      low concentrations by tandem mass spectrometry, raised polyclonal antibodies to
      those peptides, and used the antibodies to extract the 3 corresponding peptides
      from tryptic digests of human serum. We quantified each endogenous peptide using
      LC-MS/MS and multiple reaction monitoring with external calibrators. RESULTS: The
      detection limit for endogenous thyroglobulin in serum was 2.6 microg/L (4
      pmol/L). Direct comparison with immunoassay revealed good correlation (r(2) =
      0.81). CONCLUSIONS: Immunoaffinity peptide enrichment-tandem mass spectrometry
      can detect tryptic peptides of thyroglobulin at picomolar concentrations while
      also digesting the endogenous immunoglobulins that can potentially interfere with
      traditional immunoassays. Our observations suggest a general analytical strategy
      for using immunoaffinity isolation together with tandem mass spectrometry to
      quantify tumor antigens and other low-abundance proteins in human serum.

PMID- 18801936
TI  - Neuronal source of plasma dopamine.
AB  - BACKGROUND: Determinants of plasma norepinephrine (NE) and epinephrine
      concentrations are well known; those of the third endogenous catecholamine,
      dopamine (DA), remain poorly understood. We tested in humans whether DA enters
      the plasma after corelease with NE during exocytosis from sympathetic
      noradrenergic nerves. METHODS: We reviewed plasma catecholamine data from
      patients referred for autonomic testing and control subjects under the following
      experimental conditions: during supine rest and in response to orthostasis;
      intravenous yohimbine (YOH), isoproterenol (ISO), or glucagon (GLU), which
      augment exocytotic release of NE from sympathetic nerves; intravenous
      trimethaphan (TRI) or pentolinium (PEN), which decrease exocytotic NE release; or
      intravenous tyramine (TYR), which releases NE by nonexocytotic means. We included
      groups of patients with pure autonomic failure (PAF), bilateral thoracic
      sympathectomies (SNS-x), or multiple system atrophy (MSA), since PAF and SNS-x
      are associated with noradrenergic denervation and MSA is not. RESULTS:
      Orthostasis, YOH, ISO, and TYR increased and TRI/PEN decreased plasma DA
      concentrations. Individual values for changes in plasma DA concentrations
      correlated positively with changes in NE in response to orthostasis (r = 0.72, P
      < 0.0001), YOH (r = 0.75, P < 0.0001), ISO (r = 0.71, P < 0.0001), GLU (r = 0.47,
      P = 0.01), and TYR (r = 0.67, P < 0.0001). PAF and SNS-x patients had low plasma
      DA concentrations. We estimated that DA constitutes 2%-4% of the catecholamine
      released by exocytosis from sympathetic nerves and that 50%-90% of plasma DA has
      a sympathoneural source. CONCLUSIONS: Plasma DA is derived substantially from
      sympathetic noradrenergic nerves.

PMID- 18801937
TI  - Quantitation of serum free light chains in combination with protein
      electrophoresis and clinical information for diagnosing multiple myeloma in a
      general hospital population.
AB  - BACKGROUND: Serum free light chain (SFLC) measurements have recently come into
      use as an aid for diagnosing monoclonal gammopathy. We evaluated SFLC
      measurements in combination with serum protein electrophoresis (SPE) and clinical
      information for diagnosing multiple myeloma (MM) in a hospital population.
      METHODS: We measured SFLCs in 3818 sera received for SPE over a 1-year period
      when patient symptoms or biochemical findings suggested myeloma-related tissue
      damage (n = 1067). We reviewed SPE and SFLC results from 489 patients together
      with their final diagnoses obtained from the hospital information technology
      department. RESULTS: SFLC measurement, combined with SPE and clinical
      information, allowed identification of 95% of patients (38 of 40) with previously
      undiagnosed MM, macroglobulinemia, or primary amyloidosis. Additionally, we
      identified 45 patients with monoclonal gammopathy of undetermined significance
      (MGUS) and 4 with plasmacytoma. Of patients followed at our hospital in whom
      SFLCs were not measured, only 1 patient was diagnosed with MM. This patient had
      anemia and was mistakenly not tested for SFLCs. An abnormal kappa/lambda ratio
      was found in 26 of 29 patients with MM but also in 36 of 203 patients with renal
      impairment, polyclonal immunoresponse, or other nonhematological diagnoses. None
      of the 203 patients with nonhematological disease had a kappa/lambda ratio <0.05
      or >10. CONCLUSIONS: The combined use of SPE, SFLC measurements, and clinical
      criteria allows MM to be efficiently diagnosed or excluded based on serum
      measurements only.

PMID- 18801938
TI  - National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines
      for the Use of Tumor Markers.

PMID- 18801939
TI  - Abnormal matrix remodeling in adolescents and young adults with Kawasaki disease
      late after onset.
AB  - BACKGROUND: Patients with a history of Kawasaki disease (KD), have been found to
      have pericoronary and myocardial fibrosis. Serum biomarkers of fibrosis may be
      sensitive indices for detection of these late cardiac complications in KD
      patients. METHODS: We studied a cohort of 60 adolescents and young adults
      comprising 10 KD patients with persistent coronary artery lesions (CAL) occurring
      at a mean (SD) time of 14.5 (4.4) years after disease onset, 25 KD patients with
      no CAL after disease onset, and 25 healthy age-matched volunteers. We compared
      laboratory data from the patients and volunteers, including lipid profile, liver
      function, amino-terminal propeptide of type III procollagen (PIIINP), matrix
      metalloproteinase 9 (MMP-9), tissue inhibitor of metalloproteinase 1 (TIMP-1),
      and MMP-9:TIMP-1 ratios. Severity of CAL was determined on the basis of computed
      tomography determinations of the frequency of aneurysms and the extent of
      coronary stenosis/occlusion, thrombosis, and calcification. RESULTS: Increased
      PIIINP and decreased MMP-9 and TIMP-1 concentrations and decreased MMP-9:TIMP-1
      ratios were found not only in KD patients with persistent CAL but also in KD
      patients without CAL, although to a lesser extent in the latter group. In KD
      patients, the concentrations of PIIINP were positively associated with the
      severity of coronary stenosis/occlusion (r = 0.72, P = 0.011) and with the extent
      of coronary thrombus (r = 0.64, P = 0.014). The concentrations of high
      sensitivity C-reactive protein, however, did not differ across groups.
      CONCLUSIONS: Our results demonstrate alterations in extracellular matrix
      biomarkers in KD patients, suggesting enhanced collagen synthesis and ameliorated
      degradation in adolescents and young adults late after the onset of KD. We also
      observed an association between the concentrations of PIIINP and the extent of
      coronary stenosis/occlusion or thrombosis in KD patients, a finding that needs
      confirmation in further studies.

PMID- 18801940
TI  - Simultaneous measurement of serum testosterone and dihydrotestosterone by liquid
      chromatography-tandem mass spectrometry.
AB  - BACKGROUND: Recent reports have described inherent problems with androgen
      immunoassays compared with mass spectrometry analyses. METHODS: We developed a
      method for measuring serum testosterone (T) and 5alpha-dihydrotestosterone (DHT)
      simultaneously via liquid-liquid extraction followed by liquid chromatography
      tandem mass spectrometry (LC-MS/MS) with positive-mode electrospray ionization.
      RESULTS: The DHT and T calibrators showed a linear response from 0.069 nmol/L to
      34.4 nmol/L and 69.3 nmol/L, respectively. T interference in the DHT assay and
      vice versa were negligible. Within- and between-run imprecision values were <5%
      for both analytes. Percent recoveries of T and DHT spiked into samples at
      concentrations spanning the calibration curve were 100%-113% and 98%-107%,
      respectively. The lower limit of quantification was 0.069 nmol/L for both
      steroids. Serum T concentrations measured by LC-MS/MS were different from those
      obtained by RIA, especially at lower T concentrations. Serum DHT concentrations
      measured by LC-MS/MS were markedly lower than those generated by RIA because of
      the nonselectivity of the RIA without chromatography. The reference intervals
      (mean +/- 2 SDs) determined for T and DHT were 9.2-33.7 nmol/L and 0.47-2.65
      nmol/L, respectively, for 113 healthy adult men and 0.33-2.02 nmol/L and 0.09
      0.91 nmol/L, respectively, for 133 healthy premenopausal women. CONCLUSIONS: We
      have developed and validated a selective and precise method for simultaneous
      measurements of serum T and DHT that can be adopted for routine measurements of
      these androgens in health and disease in men and women.

PMID- 18801941
TI  - Increased plasma concentrations of cytoskeletal and Ca2+-binding proteins and
      their peptides in psoriasis patients.
AB  - BACKGROUND: The mechanisms underlying psoriatic pathogenesis are not fully
      understood and might be elucidated by identifying novel disease-related molecular
      markers, including autoantigens. METHODS: We used 2 proteomic methods to analyze
      plasma samples from 20 psoriasis patients and 20 matched healthy donors. The
      first method focused on evaluating changes in glycoprotein concentrations and the
      plasma proteome, and the second method assessed endogenous proteolytic activity
      by analyzing the low molecular weight component of plasma. RESULTS: The
      integrated proteomic and peptidomic analysis identified a number of proteins and
      their fragments present at different concentrations in the plasma of psoriasis
      patients and healthy donors. We used ELISA to independently verify the changes in
      the concentrations of several of these proteins. One intriguing finding,
      increased concentrations of cytoskeletal and actin-binding proteins and their
      peptides in psoriatic plasma, suggested disease-related cell leakage of these
      proteins and their increased proteolysis. Among the increased proteins and
      peptides were thymosin beta 4, talin 1, actin gamma, filamin, and profilin.
      Increased concentrations of Ca(2+)-binding proteins calgranulins A and B in
      psoriatic plasma were also observed, confirming previous reports, and appeared to
      be relevant to the increase of cytoskeletal components. Another notable change in
      psoriatic plasma was a striking decrease in fibrinogen fragments. CONCLUSIONS:
      The identified increased concentrations of cytoskeletal proteins, their peptides,
      and calgranulins in psoriatic plasma, as well as the underlying altered protease
      activity, are proposed to be related to psoriasis pathogenesis.

PMID- 18801942
TI  - Characteristic complications after autologous chondrocyte implantation for
      cartilage defects of the knee joint.
AB  - BACKGROUND: Although autologous chondrocyte implantation (ACI) is a well
      established therapy for the treatment of isolated cartilage defects of the knee
      joint, little is known about typical complications and their treatment after ACI.
      HYPOTHESIS: Unsatisfactory outcome after ACI is associated with technique-related
      typical complications. STUDY DESIGN: Case series; Level of evidence, 4. METHODS:
      A total of 309 consecutive patients with 349 ACI procedures of the knee joint
      were analyzed. Three different ACI techniques were used: periosteum-covered ACI
      in 52 cases (14.9%), Chondrogide (Geistlich Biomaterials, Wolhusen, Switzerland)
      membrane-covered ACI in 215 cases (61.6%), and a 3-dimensional matrix-associated
      ACI (BioSeed-C, Biotissue Technologies, Freiburg, Germany) in 82 cases (23.5%).
      In 52 patients, revision surgery was performed for persistent clinical problems.
      These patients were analyzed for defect size and location, technique of ACI, and
      intraoperative findings during revision surgery. The mean time of follow-up for
      patients after ACI was 4.5 years (standard deviation, +/- 1.5). RESULTS: Four
      typical major complications were identified: hypertrophy of the transplant,
      disturbed fusion of the regenerative cartilage and the healthy surrounding
      cartilage, insufficient regenerative cartilage, and delamination. These diagnoses
      covered a total of 88.5% of the patients who underwent revision surgery. The
      overall complication rate was highest in the group of patients treated with
      periosteum-covered ACI (P = .008). The incidence of symptomatic hypertrophy was
      5.2% for all techniques and defect locations; the highest incidence was in
      patients treated with periosteum-covered ACI (15.4%) (P = .001). The incidence of
      disturbed fusion was highest in the Chondrogide-covered ACI (3.7%) and the matrix
      associated ACI group (4.8%). Concerning the incidence of complications by defect
      location, there was a tendency for increased complications in patellar defects (P
      = .095). Within the patellar defects group, no correlation was found for the
      occurrence of delamination, insufficient regeneration, and disturbed fusion. As a
      statistical trend, an increased rate of hypertrophy was found for patellar
      defects (P = .091). CONCLUSION: A major proportion of complications after ACI can
      be summarized by 4 major diagnoses (symptomatic hypertrophy, disturbed fusion,
      delamination, and graft failure). Among those, the overall complication rate and
      incidence of hypertrophy of the transplant were higher for periosteum-covered
      ACI. Furthermore, an increased rate of symptomatic hypertrophy was found for
      patellar defects. Therapeutic concepts need to be developed to treat these
      typical complications of ACI.

PMID- 18801943
TI  - Habitual physical activity and sports participation after total ankle
      arthroplasty.
AB  - BACKGROUND: There is a lack of detailed information about habitual physical
      activity levels and the sports participation of patients after total ankle
      arthroplasty. HYPOTHESIS: The proportion of sports active patients increases
      after total ankle arthroplasty, and the majority of patients will meet current
      recommendations for health-enhancing physical activity. STUDY DESIGN: Case
      series; Level of evidence, 4. METHODS: The authors assessed the pre- and
      postoperative participation in sports and recreational activities of 101 patients
      at a mean of 3.7 years after total ankle arthroplasty. Activity levels were
      determined with use of the University of California at Los Angeles (UCLA)
      activity scale. The International Physical Activity Questionnaire (IPAQ) was used
      to quantify habitual physical activity levels and to calculate the proportion of
      patients meeting current guidelines for health-enhancing physical activity. The
      American Orthopaedic Foot and Ankle Society (AOFAS) hindfoot score was used as
      the clinical outcome measure. Radiographs were studied for tibial and talar
      radiolucencies, and any association between radiolucencies, activity levels, and
      sports participation was determined. RESULTS: Preoperatively, 62.4% of the
      patients were active in sports; 66.3% were active after surgery (P=.56). The
      patients were active in 3.0 +/- 1.8 different sports and recreational activities
      preoperatively and in 3.0 +/- 1.6 activities after surgery (P =1.0). The sports
      frequency remained unchanged, with 2.0 +/- 1.6 sessions per week before total
      ankle arthroplasty and 2.3 +/- 1.7 sessions per week postoperatively (P=.19).
      Overall, the patients were active in sports and recreation for 3.9 +/- 3.8 hours
      per week pre-operatively, and for 4.7 +/- 3.9 hours per week after surgery
      (P=.14). The most common disciplines after total ankle arthroplasty were
      swimming, cycling, and fitness/weight training. Sixty-five percent of the
      patients stated that surgery had improved their sports ability. The UCLA activity
      levels increased significantly from 4.3 +/- 2.2 to 6.2 +/- 1.6 (P<.001); AOFAS
      scores also improved significantly from 45.5 +/- 16.6 to 84.3 +/- 13.3 (P<.001).
      Patients suffering from posttraumatic ankle osteoarthritis were less satisfied
      with surgery than those with primary or inflammatory ankle osteoarthritis.
      Seventy-nine percent of the patients met the current guidelines for health
      enhancing physical activity according to the IPAQ. Neither sports participation
      nor activity levels were associated with the presence of periprosthetic
      radiolucencies. CONCLUSION: Two-thirds of the patients were active in sports
      after total ankle arthroplasty, and the majority of the patients met current
      health-enhancing physical activity recommendations. The clinical outcome as
      determined by AOFAS scores and the patient satisfaction were favorable. The
      present study found no association between sports participation, increased
      physical activity levels, and the appearance of periprosthetic radiolucencies 3.7
      years after total ankle arthroplasty. However, these results have to be confirmed
      after longer follow-up, in particular of those patients regularly participating
      in sports with higher impact.

PMID- 18801944
TI  - Knee immobilization for pain control after a hamstring tendon anterior cruciate
      ligament reconstruction: a randomized clinical trial.
AB  - BACKGROUND: This study will attempt to evaluate the efficacy of knee
      immobilization on patient pain levels after an anterior cruciate ligament
      reconstruction. HYPOTHESIS: There is no difference in visual analog scale pain
      scores 2 days after anterior cruciate ligament reconstruction between patients
      who wear a knee immobilizer and those who do not wear a knee immobilizer. STUDY
      DESIGN: Randomized clinical trial; Level of evidence, 1. METHODS: Patients aged
      18 to 40 years who met study inclusion criteria were eligible. Patients meeting
      intraoperative inclusion criteria were randomized (immobilizer or no immobilizer)
      after wound closure. The immobilizer used was a soft, unhinged brace with Velcro
      straps. Preoperative, intraoperative, and postoperative protocols were
      standardized. The primary outcome was patient self-assessed pain using a 0-to-100
      mm visual analog scale at day 2 after surgery. Secondary outcomes included pain
      and analgesic use in the first 14 days after surgery, complications, and range of
      motion (approximately 3 weeks postoperatively). A sample size estimate was
      calculated and resulted in the need for 44 patients per group. RESULTS: A total
      of 102 patients were enrolled; 88 patients were randomized, and 14 were excluded
      intraoperatively. There was no difference in mean visual analog scale pain scores
      at 2 days after surgery between immobilized and nonimmobilized patients (32.6 and
      35.2, respectively; P = .59; difference, -2.6; 95% confidence interval, -12.2 to
      6.9). There were no differences between groups in medication consumed, range of
      motion, or complications. Pain and analgesic use were the same for both groups at
      7 and 14 days postoperatively. CONCLUSION: No differences in pain or any of the
      secondary outcomes were detected between immobilized and nonimmobilized patients
      at any point during the first 14 days after anterior cruciate ligament
      reconstruction.

PMID- 18801945
TI  - The molecular mechanism of "ryegrass staggers," a neurological disorder of K+
      channels.
AB  - "Ryegrass staggers" is a neurological condition of unknown mechanism that impairs
      motor function in livestock. It is caused by infection of perennial ryegrass
      pastures by an endophytic fungus that produces neurotoxins, predominantly the
      indole-diterpenoid compound lolitrem B. Animals grazing on such pastures develop
      uncontrollable tremors and become uncoordinated in their movement. Lolitrem B and
      the structurally related tremor inducer paxilline both act as potent large
      conductance calcium-activated potassium (BK) channel inhibitors. Using patch
      clamping, we show that their different apparent affinities correlate with their
      toxicity in vivo. To investigate whether the motor function deficits produced by
      lolitrem B and paxilline are due to inhibition of BK ion channels, their ability
      to induce tremor and ataxia in mice deficient in this ion channel (Kcnma1(-/-))
      was examined. Our results show that mice lacking Kcnma1 are unaffected by these
      neurotoxins. Furthermore, doses of these substances known to be lethal to wild
      type mice had no effect on Kcnma1(-/-) mice. These studies reveal the BK channel
      as the molecular target for the major components of the motor impairments induced
      by ryegrass neurotoxins. Unexpectedly, when the response to lolitrem B was
      examined in mice lacking the beta4 BK channel accessory subunit (Kcnmb4(-/-)),
      only low-level ataxia was observed. Our study therefore reveals a new role for
      the accessory BK beta4 subunit in motor control. The beta4 subunit could be
      considered as a potential target for treatment of ataxic conditions in animals
      and in humans.

PMID- 18801946
TI  - NIM811 (N-methyl-4-isoleucine cyclosporine), a mitochondrial permeability
      transition inhibitor, attenuates cholestatic liver injury but not fibrosis in
      mice.
AB  - Cholestasis causes hepatocyte death, possibly because of mitochondrial injury.
      This study investigated whether NIM811 (N-methyl-4-isoleucine cyclosporine), an
      inhibitor of the mitochondrial permeability transition (MPT), attenuates
      cholestatic liver injury in vivo. Cholestasis was induced in mice by bile duct
      ligation (BDL). NIM811 was gavaged (20 mg/kg) before BDL and daily (10 mg/kg)
      afterward. Mitochondrial depolarization, cell death, and MPT onset were assessed
      by intravital confocal/multiphoton microscopy of rhodamine 123, propidium iodide,
      and calcein. After BDL, serum alanine aminotransferase (ALT), hepatic necrosis,
      and apoptosis all increased. NIM811 decreased ALT, necrosis, and apoptosis by 60
      to 86%. In vehicle-treated mice at 6 h after BDL, viable hepatocytes with
      depolarized mitochondria were 18/high-power field (hpf), and nonviable cells were
      approximately 1/hpf, showing that depolarization preceded necrosis. Calcein
      entered mitochondria after BDL, indicating MPT onset in vivo. NIM811 decreased
      depolarization by 72%, prevented calcein entry into mitochondria, and blocked
      release of cytochrome c. Hepatic tumor necrosis factor alpha, transforming growth
      factor-beta1, procollagen alpha1(I) mRNA, alpha-smooth muscle actin, and Sirius
      red staining for collagen increased after BDL but were not different in vehicle-
      and NIM811-treated mice. Taken together, NIM811 decreased cholestatic necrosis
      and apoptosis but did not block fibrosis, indicating that the MPT plays an
      important role in cholestatic cell death in vivo.

PMID- 18801947
TI  - Antidepressants targeting the serotonin reuptake transporter act via a
      competitive mechanism.
AB  - Although several antidepressants (including fluoxetine, imipramine, citalopram,
      venlafaxine, and duloxetine) are known to inhibit the serotonin transporter
      (SERT), whether or not these molecules compete with 5-hydroxytryptamine
      (serotonin) (5-HT) for binding to SERT has remained controversial. We have
      performed radioligand competition binding experiments and found that all data can
      be fitted via a simple competitive interaction model, using Cheng-Prusoff
      analysis (Biochem Pharmacol 22:3099-3108, 1973). Two different SERT-selective
      radioligands, [(3)H]N,N-dimethyl-2-(2-amino-4-cyanophenyl thio)-benzylamine
      (DASB) and [(3)H]S-citalopram, were used to probe competitive binding to
      recombinantly expressed human SERT or native SERT in rat cortical membranes. All
      the SERT inhibitors that we tested were able to inhibit [(3)H]DASB and [(3)H]S
      citalopram binding in a concentration-dependent manner, with unity Hill
      coefficient. In accordance with the Cheng-Prusoff relationship for a competitive
      interaction, we observed that test compound concentrations associated with 50%
      maximal inhibition of radiotracer binding (IC(50)) increased linearly with
      increasing radioligand concentration for all ligands: 5-HT, S-citalopram, R
      citalopram, paroxetine, clomipramine, fluvoxamine, imipramine venlafaxine,
      duloxetine, indatraline, cocaine, and 2-beta-carboxy-3-beta-(4
      iodophenyl)tropane. The equilibrium dissociation constant of 5-HT and SERT
      inhibitors were also derived using Scatchard analysis of the data set, and they
      were found to be comparable with the data obtained using the Cheng-Prusoff
      relationship. Our studies establish a reference framework that will contribute to
      ongoing efforts to understand ligand binding modes at SERT by demonstrating that
      5-HT and the SERT inhibitors tested bind to the serotonin transporter in a
      competitive manner.

PMID- 18801948
TI  - Kinetic and thermodynamic assessment of binding of serotonin transporter
      inhibitors.
AB  - Several serotonin reuptake inhibitors are in clinical use for treatment of
      depression and anxiety disorders. However, to date, reported pharmacological
      differentiation of these ligands has focused mainly on their equilibrium binding
      affinities for the serotonin transporter. This study takes a new look at
      antidepressant binding modes using radioligand binding assays with [(3)H]S
      citalopram to determine equilibrium and kinetic rate constants across multiple
      temperatures. The observed dissociation rate constants at 26 degrees C fall into
      a narrow range for all molecules. Conversely, association rate constants
      generally decreased with increasing equilibrium binding affinities. Consistent
      with this, the measured activation energy for S-citalopram association was
      relatively large (19.5 kcal . mol(-1)), suggesting conformational change upon
      ligand binding. For most of the drugs, including citalopram, the enthalpy
      (DeltaH(O)) and entropy (-TDeltaS(O)) contributions to reaction energetics were
      determined by van't Hoff analyses to be roughly equivalent (25-75% DeltaG(O)) and
      to correlate (positively for enthalpy) with the polar surface area of the drug.
      However, the binding of the drug fluvoxamine was predominantly entropically
      driven. When these data are considered in the context of the physicochemical
      properties of these ligands, two distinct binding modes can be proposed. The
      citalopram-type binding mode probably uses a polar binding pocket that allows
      charged or polar interactions between ligand and receptor with comparatively
      small loss in enthalpy due to dehydration. The fluvoxamine-type binding mode is
      fueled by energy released upon burying hydrophobic ligand moieties into a binding
      pocket that is flexible enough to suffer minimal loss in entropy from
      conformational constraint.

PMID- 18801949
TI  - Gene expression profiles in livers from diclofenac-treated rats reveal intestinal
      bacteria-dependent and -independent pathways associated with liver injury.
AB  - Diclofenac (DCLF) is a nonsteroidal anti-inflammatory drug that is associated
      with idiosyncratic adverse drug reactions in humans. Previous studies revealed a
      crucial role for intestine-derived bacteria and/or lipopolysaccharide (LPS) in
      DCLF-induced hepatotoxicity. We further explored this mechanism by conducting
      gene expression analysis of livers from rats treated with a hepatotoxic dose of
      DCLF (100 mg/kg) with or without oral antibiotic pretreatment. Genes for which
      expression was altered by DCLF were divided into two groups: genes with
      expression altered by antibiotic treatment and those unaffected by antibiotics.
      The former group of genes represented the ones for which DCLF-induced alterations
      in expression depended on intestinal bacteria. The expression of the latter group
      of genes was probably changed by direct effect of DCLF rather than by intestinal
      bacteria. Functional analysis of genes in the former group revealed LPS-related
      signaling, further suggesting a role for bacterial endotoxin in the liver injury.
      Functional analysis of genes in the latter group revealed changes in signaling
      pathways related to inflammation, hypoxia, oxidative stress, the aryl hydrocarbon
      receptor, and peroxisome proliferator-activated receptor alpha. Neutrophil
      depletion failed to protect from DCLF-induced hepatotoxicity, suggesting that
      intestinal bacteria contribute to liver injury in a neutrophil-independent
      manner. Hypoxia occurred in the livers of rats treated with DCLF, and hypoxia in
      vitro rendered hepatocytes sensitive to DCLF-induced cytotoxicity. These results
      support the hypothesis that intestinal bacteria are required for DCLF-induced
      hepatotoxicity and suggest that hypoxia plays an important role in the
      pathogenesis.

PMID- 18801950
TI  - Voriconazole-induced photosensitivity.
AB  - Voriconazole is a broad-spectrum triazole antifungal agent indicated for invasive
      aspergillosis, refractory Candida infections, and other emerging invasive fungal
      infections. Adverse cutaneous reactions associated with voriconazole therapy
      occur in fewer than 10% of treated patients and range from mild erythematous
      eruptions to life-threatening reactions such as the Stevens-Johnson syndrome and
      toxic epidermal necrolysis. Photosensitivity reactions are an uncommon but
      characteristic dermatitis in voriconazole recipients, particularly following
      chronic administration. We report a case of voriconazole-induced phototoxicity in
      a 50-year-old male with Candida parapsilosis endocarditis that reversed on
      discontinuation of the drug.

PMID- 18801951
TI  - Surgical pearl: the pendulum or "scoop" biopsy.

PMID- 18801952
TI  - Prognostic significance of 18 F-fluorodeoxyglucose - positron emission tomography
      after treatment in patients with limited stage small cell lung cancer.
AB  - OBJECTIVE: Small cell lung cancer (SCLC) represents 15% to 25% of lung cancers.
      Despite favorable initial treatment response rates, recurrence is likely and long
      term prognosis dismal. Accurate measurement of therapy response is critical to
      determine which patients might be spared additional treatment, and potential side
      effects. (18)F-fluorodeoxyglucose positron emission tomography (PET) may help
      distinguish necrotic or fibrous tissue from residual cancer, thus informing
      further treatment and prognosis. DESIGN/SETTING/PARTICIPANTS AND METHODS:
      Retrospective chart review study of limited stage SCLC patients with PET scanning
      within 4 months post-chemotherapy at Marshfield Clinic, Marshfield, Wisconsin.
      Diagnosis of SCLC occurred from December 1, 2001 through December 31, 2007.
      RESULTS: Twenty-two patients (approximately 7%) had post-treatment PET: 11
      positive, 11 negative. Median duration from last chemotherapy to PET was 36 days
      (range, 3 to 125 days). Median follow-up for all patients was 34.4 months (range,
      6.8 to 65.9 months). Estimated median progression-free survival for all patients
      was 8.1 months (95% confidence intervals [CI], 4.3 to 11.9 months), 10.5 months
      for PET negative (95% CI, 8.1 to >57.8 months) and 4.3 months for PET positive
      patients (95% CI, 2.8 to >7.2 months) (P<0.007, log-rank test). Median survival
      for all patients was 19.2 months (95% CI, 10.3 to >65.8 months). Estimated median
      survival for PET negative patients was longer than PET positive (29.2 versus 10.3
      months, P=0.10). CONCLUSION: Post-treatment PET, prognostically significant, may
      be underutilized.

PMID- 18801954
TI  - Point: the interpolated twitch does/does not provide a valid measure of the
      voluntary activation of muscle.

PMID- 18801955
TI  - Advancing femoral nerve stimulation into the stage of science.

PMID- 18801953
TI  - Insulin analogs: impact on treatment success, satisfaction, quality of life, and
      adherence.
AB  - A growing body of medical research has demonstrated that intensive control of
      serum glucose levels can minimize the development of diabetes-related
      complications. Success with insulin management ultimately depends on how closely
      a given regimen can mimic normal physiologic insulin release patterns. The new
      insulin analogs, including the rapid-acting analogs (aspart, lispro, glulisine),
      the long-acting basal analogs (glargine, detemir), and the premixed insulin
      analog formulations (75% neutral protamine lispro, 25% lispro; 50% neutral
      protamine lispro, 50% lispro; 70% protamine aspart, 30% aspart) have been
      formulated to allow for a closer replication of a normal insulin profile. The
      rapid-acting analogs can be administered at mealtimes and produce a rapid and
      short-lived insulin spike to address postprandial glucose elevations, while the
      long-acting analogs come close to the ideal of a smooth, relatively flat, 24-hour
      basal insulin supply, with less variability in action compared to NPH insulin.
      Despite these clear pharmacologic advantages, measurable clinical benefits in a
      complex disease such as diabetes can be hard to measure. To date, reviews of
      insulin analog studies have not found a dramatic overall improvement in
      glycosylated hemoglobin (HbA1c) outcomes compared to traditional human insulins,
      although all-analog basal-bolus regimens were associated with significantly lower
      HbA1c than all-human-insulin basal bolus regimens in some studies. Beyond HbA1c
      comparisons, however, insulin analogs have been shown in many instances to be
      associated with lower risks of hypoglycemia, lower levels of postprandial glucose
      excursions, better patient adherence, greater quality of life, and higher
      satisfaction with treatment. The long-acting basal analog insulin detemir has the
      additional advantage of producing less weight gain, which has been considered
      until now an almost inevitable consequence of insulin replacement.

PMID- 18801956
TI  - Nitric oxide inhibits cutaneous vasoconstriction to exogenous norepinephrine.
AB  - Previously, we found that nitric oxide (NO) inhibits cutaneous vasoconstrictor
      responsiveness evoked by whole body cooling, as well as an orthostatic stress in
      the heat-stressed human (Shibasaki M, Durand S, Davis SL, Cui J, Low DA, Keller
      DM, Crandall CG. J Physiol 585: 627-634, 2007). However, it remains unknown
      whether this response occurs via NO acting through presynaptic or postsynaptic
      mechanisms. The aim of this study was to test the hypothesis that NO is capable
      of impairing cutaneous vasoconstriction via postsynaptic mechanisms. Skin blood
      flow was monitored over two forearm sites where intradermal microdialysis
      membranes were previously placed. Skin blood flow was elevated four- to fivefold
      through perfusion of the NO donor sodium nitroprusside at one site and through
      perfusion of adenosine (primarily non-NO mechanisms) at a second site. Once a
      plateau in vasodilation was evident, increasing concentrations of norepinephrine
      (1 x 10(-8) to 1 x 10(-2) M) were administrated through both microdialysis
      probes, while the aforementioned vasodilator agents continued to be perfused.
      Cutaneous vascular conductance was calculated by dividing skin blood flow by mean
      arterial blood pressure. The administration of norepinephrine decreased cutaneous
      vascular conductance at both sites. However, the dose of norepinephrine at the
      onset of vasoconstriction (-5.9 +/- 1.3 vs. -7.2 +/- 0.7 log M norepinephrine, P
      = 0.021) and the concentration of norepinephrine resulting in 50% of the maximal
      vasoconstrictor response (-4.9 +/- 1.2 vs. -6.1 +/- 0.2 log M norepinephrine
      dose; P = 0.012) occurred at significantly higher norepinephrine concentrations
      for the sodium nitroprusside site relative to the adenosine site, respectively.
      These results suggested that NO is capable of attenuating cutaneous
      vasoconstrictor responsiveness to norepinephrine via postsynaptic mechanisms.

PMID- 18801957
TI  - Evidence of skeletal muscle damage following electrically stimulated isometric
      muscle contractions in humans.
AB  - It is unknown whether muscle damage at the level of the sarcomere can be induced
      without lengthening contractions. To investigate this, we designed a study where
      seven young, healthy men underwent 30 min of repeated electrical stimulated
      contraction of m. gastrocnemius medialis, with the ankle and leg locked in a
      fixed position. Two muscle biopsies were collected 48 h later: one from the
      stimulated muscle and one from the contralateral leg as a control. The biopsies
      were analyzed immunohistochemically for inflammatory cell infiltration and
      intermediate filament disruption. Ultrastructural changes at the level of the z
      lines were investigated by transmission electron microscopy. Blood samples were
      collected for measurement of creatine kinase activity, and muscle soreness was
      assessed in the days following stimulation. The biopsies from the stimulated
      muscle revealed macrophage infiltration and desmin-negative staining in a small
      percentage of myofibers in five and four individuals, respectively. z-Line
      disruption was evident at varying magnitudes in all subjects and displayed a
      trend toward a positive correlation (r = 0.73, P = 0.0663) with the force
      produced by stimulation. Increased muscle soreness in all subjects, combined with
      a significant increase in creatine kinase activity (P < 0.05), is indirectly
      suggestive of muscle damage, and the novel findings of the present study, i.e.,
      1) macrophages infiltration, 2) lack of desmin staining, and 3) z-line
      disruption, provide direct evidence of damage at the myofiber and sarcomere
      levels. These data support the hypothesis that muscle damage at the level of the
      sarcomere can be induced without lengthening muscle contractions.

PMID- 18801958
TI  - Selective vulnerability of the inner ear to decompression sickness in divers with
      right-to-left shunt: the role of tissue gas supersaturation.
AB  - Inner ear decompression sickness has been strongly associated with the presence
      of right-to-left shunts. The implied involvement of intravascular bubbles shunted
      from venous to arterial circulations is inconsistent with the frequent absence of
      cerebral symptoms in these cases. If arterial bubbles reach the labyrinthine
      artery, they must also be distributing widely in the brain. This discrepancy
      could be explained by slower inert gas washout from the inner ear after diving
      and the consequent tendency for arterial bubbles entering this supersaturated
      territory to grow because of inward diffusion of gas. Published models for inner
      ear and brain inert gas kinetics were used to predict tissue gas tensions after
      an air dive to 4 atm absolute for 25 min. The models predict half-times for
      nitrogen washout of 8.8 min and 1.2 min for the inner ear and brain,
      respectively. The inner ear remains supersaturated with nitrogen for longer after
      diving than the brain, and in the simulated dive, for a period that corresponds
      with the latency of typical cases. It is therefore plausible that prolonged inner
      ear inert gas supersaturation contributes to the selective vulnerability of the
      inner ear to short latency decompression sickness in divers with right-to-left
      shunt.

PMID- 18801959
TI  - Anti-TNF treatment reduces rat skeletal muscle wasting in monocrotaline-induced
      cardiac cachexia.
AB  - The aim was to explore efficacy of tumor necrosis factor (TNF) inhibitors in
      attenuating increases in anorexia and ubiquitin proteasome pathway transcripts in
      cardiac cachexia, a potentially lethal condition that responds poorly to current
      treatments. Cardiac cachexia was rapidly induced with monocrotaline in Sprague
      Dawley rats. Either soluble TNF receptor-1 or the general inhibitor of TNF
      production, pentoxifylline, was given to diminish TNF action on the first
      indication of cachexia. Animals were anesthetized with a ketamine-xylazine
      acepromazine cocktail, and then skeletal muscles were removed for subsequent
      measurements including ubiquitin proteasome pathway transcripts and Western
      blots. Both soluble TNF receptor-1 and pentoxifylline attenuated losses in both
      body and skeletal muscle masses and also reduced increases in selected ubiquitin
      proteasome pathway transcripts. The action of soluble TNF receptor-1 was partly
      through reversal of reduced food consumption, while the effects of pentoxifylline
      were independent of food intake. Here we demonstrate, for the first time, that
      attenuation of anorexia by soluble TNF receptor-1 treatment in monocrotaline
      induced cardiac cachexia is responsible for attenuating increases in some
      ubiquitin proteasome pathway transcripts as well as preserving body mass and
      attenuating loss of skeletal muscle mass.

PMID- 18801961
TI  - Exercise enhances the proliferation of neural stem cells and neurite growth and
      survival of neuronal progenitor cells in dentate gyrus of middle-aged mice.
AB  - Aging is an important determinant of adult hippocampal neurogenesis as the
      proliferation of neural stem/precursor cells (NSCs) declines dramatically before
      middle age. Contrary to this, physical exercise is known to promote adult
      hippocampal neurogenesis. The objective of this study is to investigate the
      effects of mandatory treadmill running (TR) on neurogenesis, including 1) NSCs
      proliferation, 2) neurite outgrowth of neuronal progenitor cells, and 3) the
      survival of newborn neurons in dentate area of middle-aged animals. Compared with
      3-mo-old mice, numbers of mitotic cells and neuronal progenitor cells decreased
      dramatically by middle age and remained at low levels after middle age. Five
      weeks of TR not only increased NSC proliferation and the number of immature
      neurons but also promoted the maturation and survival of immature neurons in
      middle-aged mice. The neurogenic and neurotrophic effects of TR were not due to
      the reduction of the age-related elevation of serum corticosterone.
      Significantly, 5 wk of TR restored the age-dependent decline of brain-derived
      neurotrophic factor and its receptor, TrkB, which are known to promote neuronal
      differentiation and survival. Taken together, mandatory running exercise alters
      the brain chemistries of middle-aged animals toward an environment that is
      favorable to NSC proliferation, survival, and maturation.

PMID- 18801960
TI  - Age-dependent increase in oxidative stress in gastrocnemius muscle with
      unloading.
AB  - Oxidative stress increases during unloading in muscle from young adult rats. The
      present study examined the markers of oxidative stress and antioxidant enzyme
      gene and protein expressions in medial gastrocnemius muscles of aged and young
      adult (30 and 6 mo of age) Fischer 344 x Brown Norway rats after 14 days of
      hindlimb suspension. Medial gastrocnemius muscle weight was decreased by
      approximately 30% in young adult and aged rats following suspension. When muscle
      weight was normalized to animal body weight, it was reduced by 12% and 22% in
      young adult and aged rats, respectively, after suspension. Comparisons between
      young adult and aged control animals demonstrated a 25% and 51% decline in muscle
      mass when expressed as absolute muscle weight and muscle weight normalized to the
      animal body weight, respectively. H(2)O(2) content was elevated by 43% while Mn
      superoxide dismutase (MnSOD) protein content was reduced by 28% in suspended
      muscles compared with control muscles exclusively in the aged animals. Suspended
      muscles had greater content of malondialdehyde (MDA)/4-hydroxyalkenals (4-HAE)
      (29% and 58% increase in young adult and aged rats, respectively), nitrotyrosine
      (76% and 65% increase in young adult and aged rats, respectively), and catalase
      activity (69% and 43% increase in young adult and aged rats, respectively)
      relative to control muscles. Changes in oxidative stress markers MDA/4-HAE,
      H(2)O(2), and MnSOD protein contents in response to hindlimb unloading occurred
      in an age-dependent manner. These findings are consistent with the hypotheses
      that oxidative stress has a role in mediating disuse-induced and sarcopenia
      associated muscle losses. Our data suggest that aging may predispose skeletal
      muscle to increased levels of oxidative stress both at rest and during unloading.

PMID- 18801962
TI  - Effects of inspiratory pause on CO2 elimination and arterial PCO2 in acute lung
      injury.
AB  - A high respiratory rate associated with the use of small tidal volumes,
      recommended for acute lung injury (ALI), shortens time for gas diffusion in the
      alveoli. This may decrease CO(2) elimination. We hypothesized that a
      postinspiratory pause could enhance CO(2) elimination and reduce Pa(CO(2)) by
      reducing dead space in ALI. In 15 mechanically ventilated patients with ALI and
      hypercapnia, a 20% postinspiratory pause (Tp20) was applied during a period of 30
      min between two ventilation periods without postinspiratory pause (Tp0). Other
      parameters were kept unchanged. The single breath test for CO(2) was recorded
      every 5 min to measure tidal CO(2) elimination (VtCO(2)), airway dead space
      (V(Daw)), and slope of the alveolar plateau. Pa(O(2)), Pa(CO(2)), and
      physiological and alveolar dead space (V(Dphys), V(Dalv)) were determined at the
      end of each 30-min period. The postinspiratory pause, 0.7 +/- 0.2 s, induced on
      average <0.5 cmH(2)O of intrinsic positive end-expiratory pressure (PEEP). During
      Tp20, VtCO(2) increased immediately by 28 +/- 10% (14 +/- 5 ml per breath
      compared with 11 +/- 4 for Tp0) and then decreased without reaching the initial
      value within 30 min. The addition of a postinspiratory pause significantly
      decreased V(Daw) by 14% and V(Dphys) by 11% with no change in V(Dalv). During
      Tp20, the slope of the alveolar plateau initially fell to 65 +/- 10% of baseline
      value and continued to decrease. Tp20 induced a 10 +/- 3% decrease in Pa(CO(2))
      at 30 min (from 55 +/- 10 to 49 +/- 9 mmHg, P < 0.001) with no significant
      variation in Pa(O(2)). Postinspiratory pause has a significant influence on CO(2)
      elimination when small tidal volumes are used during mechanical ventilation for
      ALI.

PMID- 18801963
TI  - Na+/H+ exchanger-1 inhibitors decrease myocardial superoxide production via
      direct mitochondrial action.
AB  - The possibility of a direct mitochondrial action of Na(+)/H(+) exchanger-1 (NHE
      1) inhibitors decreasing reactive oxygen species (ROS) production was assessed in
      cat myocardium. Angiotensin II and endothelin-1 induced an NADPH oxidase (NOX)
      dependent increase in anion superoxide (O(2)(-)) production detected by
      chemiluminescence. Three different NHE-1 inhibitors [cariporide, BIIB-723, and
      EMD-87580] with no ROS scavenger activity prevented this increase. The
      mitochondria appeared to be the source of the NOX-dependent ROS released by the
      "ROS-induced ROS release mechanism" that was blunted by the mitochondrial ATP
      sensitive potassium channel blockers 5-hydroxydecanoate and glibenclamide,
      inhibition of complex I of the electron transport chain with rotenone, and
      inhibition of the permeability transition pore (MPTP) by cyclosporin A.
      Cariporide also prevented O(2)(-) production induced by the opening of mK(ATP)
      with diazoxide. Ca(2+)-induced swelling was evaluated in isolated mitochondria as
      an indicator of MPTP formation. Cariporide decreased mitochondrial swelling to
      the same extent as cyclosporin A and bongkrekic acid, confirming its direct
      mitochondrial action. Increased O(2)(-) production, as expected, stimulated
      ERK1/2 and p90 ribosomal S6 kinase phosphorylation. This was also prevented by
      cariporide, giving additional support to the existence of a direct mitochondrial
      action of NHE-1 inhibitors in preventing ROS release. In conclusion, we report a
      mitochondrial action of NHE-1 inhibitors that should lead us to revisit or
      reinterpret previous landmark observations about their beneficial effect in
      several cardiac diseases, such as ischemia-reperfusion injury and cardiac
      hypertrophy and failure. Further studies are needed to clarify the precise
      mechanism and site of action of these drugs in blunting MPTP formation and ROS
      release.

PMID- 18801964
TI  - Fat adaptation followed by carbohydrate restoration increases AMPK activity in
      skeletal muscle from trained humans.
AB  - We have previously reported that 5 days of a high-fat diet followed by 1 day of
      high-carbohydrate intake (Fat-adapt) increased rates of fat oxidation and
      decreased rates of muscle glycogenolysis during submaximal cycling compared with
      consumption of an isoenergetic high-carbohydrate diet (HCHO) for 6 days (Burke et
      al. J Appl Physiol 89: 2413-2421, 2000; Stellingwerff et al. Am J Physiol
      Endocrinol Metab 290: E380-E388, 2006). To determine potential mechanisms
      underlying shifts in substrate selection, eight trained subjects performed Fat
      adapt and HCHO. On day 7, subjects performed 1-h cycling at 70% peak O2 uptake.
      Muscle biopsies were taken immediately before and after exercise. Resting muscle
      glycogen content was similar between treatments, but muscle triglyceride levels
      were higher after Fat-adapt (P < 0.05). Resting AMPK-alpha1 and -alpha2 activity
      was higher after Fat-adapt (P = 0.02 and P = 0.05, respectively), while the
      phosphorylation of AMPK's downstream target, acetyl-CoA carboxylase (pACC at
      Ser221), tended to be elevated after Fat-adapt (P = 0.09). Both the respiratory
      exchange ratio (P < 0.01) and muscle glycogen utilization (P < 0.05) were lower
      during exercise after Fat-adapt. Exercise increased AMPK-alpha1 activity after
      HCHO (P = 0.03) but not Fat-adapt. Exercise was associated with an increase in
      pACC at Ser221 for both dietary treatments (P < 0.05), with postexercise pACC
      Ser221 higher after Fat-adapt (P = 0.02). In conclusion, compared with HCHO, Fat
      adapt increased resting muscle triglyceride stores and resting AMPK-alpha1 and 
      alpha2 activity. Fat-adapt also resulted in higher rates of whole body fat
      oxidation, reduced muscle glycogenolysis, and attenuated the exercise-induced
      rise in AMPK-alpha1 and AMPK-alpha2 activity compared with HCHO. Our results
      demonstrate that AMPK-alpha1 and AMPK-alpha2 activity and fuel selection in
      skeletal muscle in response to exercise can be manipulated by diet and/or the
      interactive effects of diet and exercise training.

PMID- 18801965
TI  - Positive net movements of amino acids in the hindlimb after overnight food
      deprivation contribute to sustaining the elevated anabolism of neonatal pigs.
AB  - During the neonatal period, high protein breakdown rate is a metabolic process
      inherent to elevated rates of protein accretion in skeletal muscle. To determine
      the relationship between hindlimb net movements of essential and nonessential
      amino acids in the regulation of hindlimb protein breakdown during an overnight
      fasting-feeding cycle, we infused overnight-food-deprived 10- and 28-day-old
      piglets with [1-(13)C]phenylalanine and [ring-(2)H(4)]tyrosine over 7 h (during 3
      h of fasting and then during 4 h of feeding). Extraction rates for aspartate and
      glutamate after an overnight fast were 15% and 51% in the 10-day-old compared
      with 6% and 25% in the 28-day-old (P < 0.05) piglets, suggesting an altered
      requirement for precursors of amino acids to shuttle nitrogen to the liver as
      early life progresses. This occurred simultaneously with marginal positive
      hindlimb net balance of essential amino acids after an overnight fast, with
      negative net release of many nonessential amino acids, such as alanine,
      asparagine, glutamine, glycine, and proline. This suggests that newborn muscle
      does not undergo significant protein mobilization after a short period of fasting
      in support of an elevated rate of protein accretion. Furthermore, tyrosine efflux
      from hindlimb breakdown between overnight fasting and feeding periods was not
      different in the 10-day-old piglets, for which tyrosine was limiting, but when
      tyrosine supply balanced requirements in the 28-day-old piglet, hindlimb efflux
      was increased (P = 0.01). The results of the present study indicate that
      proteolysis and net movements of amino acids are coordinated mechanisms that
      sustain the elevated rate of net protein accretion during overnight feeding
      fasting cycles in the neonate.

PMID- 18801966
TI  - Enhanced airway dilation by positive-pressure inflation of the lungs compared
      with active deep inspiration in patients with asthma.
AB  - Deep inspiration temporarily reduces induced airways obstruction in healthy
      subjects. This bronchodilatory effect of deep inspiration is impaired in asthma.
      Passive machine-assisted lung inflation may augment bronchodilation compared with
      an active deep inspiration in patients with asthma by either opening closed
      airways or by reducing fluid flux across the airway wall during deep inspiration,
      and thereby increasing the tethering forces on the airway wall. We recruited 24
      patients with asthma [18-46 yr old, forced expiratory volume in 1 s (FEV(1)) >
      70% predicted; provocative concentration of methacholine inducing a 20% fall in
      FEV(1) (PC(20)) < 8 mg/ml], with either an impaired (n = 12) or an intact (n =
      12) bronchodilatory response to deep inspiration. Two methacholine challenges
      were performed on separate days. At a 50% increase in respiratory resistance
      (forced oscillation technique at 8 Hz), the change in resistance by a positive
      pressure inflation (computer-driven syringe) or an active deep inspiration was
      measured in randomized order. The reduction in resistance by positive-pressure
      inflation was significantly greater than by active deep inspiration in the
      impaired deep inspiration response group (mean change +/- SE: -0.6 +/- 0.1 vs. 
      0.03 +/- 0.2 cmH(2)O.l(-1).s, P = 0.002). No significant difference was found
      between positive-pressure inflation and active deep inspiration in the intact
      deep inspiration response group (-0.6 +/- 0.2 vs. -1.0 +/- 0.3 cmH(2)O.l(-1).s, P
      = 0.18). Positive-pressure inflation of the lungs can significantly enhance deep
      inspiration-induced bronchodilation in patients with asthma.

PMID- 18801969
TI  - A high phase-space-density gas of polar molecules.
AB  - A quantum gas of ultracold polar molecules, with long-range and anisotropic
      interactions, not only would enable explorations of a large class of many-body
      physics phenomena but also could be used for quantum information processing. We
      report on the creation of an ultracold dense gas of potassium-rubidium (40K87Rb)
      polar molecules. Using a single step of STIRAP (stimulated Raman adiabatic
      passage) with two-frequency laser irradiation, we coherently transfer extremely
      weakly bound KRb molecules to the rovibrational ground state of either the
      triplet or the singlet electronic ground molecular potential. The polar molecular
      gas has a peak density of 10(12) per cubic centimeter and an expansion-determined
      translational temperature of 350 nanokelvin. The polar molecules have a permanent
      electric dipole moment, which we measure with Stark spectroscopy to be 0.052(2)
      Debye (1 Debye = 3.336 x 10(-30) coulomb-meters) for the triplet rovibrational
      ground state and 0.566(17) Debye for the singlet rovibrational ground state.

PMID- 18801967
TI  - Innate immunity in Caenorhabditis elegans is regulated by neurons expressing NPR
      1/GPCR.
AB  - A large body of evidence indicates that metazoan innate immunity is regulated by
      the nervous system, but the mechanisms involved in the process and the biological
      importance of such control remain unclear. We show that a neural circuit
      involving npr-1, which encodes a G protein-coupled receptor (GPCR) related to
      mammalian neuropeptide Y receptors, functions to suppress innate immune
      responses. The immune inhibitory function requires a guanosine 3',5'
      monophosphate-gated ion channel encoded by tax-2 and tax-4 as well as the soluble
      guanylate cyclase GCY-35. Furthermore, we show that npr-1- and gcy-35-expressing
      sensory neurons actively suppress immune responses of nonneuronal tissues. A full
      genome microarray analysis on animals with altered neural function due to
      mutation in npr-1 shows an enrichment in genes that are markers of innate immune
      responses, including those regulated by a conserved PMK-1/p38 mitogen-activated
      protein kinase signaling pathway. These results present evidence that neurons
      directly control innate immunity in C. elegans, suggesting that GPCRs may
      participate in neural circuits that receive inputs from either pathogens or
      infected sites and integrate them to coordinate appropriate immune responses.

PMID- 18801968
TI  - White fat progenitor cells reside in the adipose vasculature.
AB  - White adipose (fat) tissues regulate metabolism, reproduction, and life span.
      Adipocytes form throughout life, with the most marked expansion of the lineage
      occurring during the postnatal period. Adipocytes develop in coordination with
      the vasculature, but the identity and location of white adipocyte progenitor
      cells in vivo are unknown. We used genetically marked mice to isolate
      proliferating and renewing adipogenic progenitors. We found that most adipocytes
      descend from a pool of these proliferating progenitors that are already
      committed, either prenatally or early in postnatal life. These progenitors reside
      in the mural cell compartment of the adipose vasculature, but not in the
      vasculature of other tissues. Thus, the adipose vasculature appears to function
      as a progenitor niche and may provide signals for adipocyte development.

PMID- 18801970
TI  - Catalytic conversion of biomass to monofunctional hydrocarbons and targeted
      liquid-fuel classes.
AB  - It is imperative to develop more efficient processes for conversion of biomass to
      liquid fuels, such that the cost of these fuels would be competitive with the
      cost of fuels derived from petroleum. We report a catalytic approach for the
      conversion of carbohydrates to specific classes of hydrocarbons for use as liquid
      transportation fuels, based on the integration of several flow reactors operated
      in a cascade mode, where the effluent from the one reactor is simply fed to the
      next reactor. This approach can be tuned for production of branched hydrocarbons
      and aromatic compounds in gasoline, or longer-chain, less highly branched
      hydrocarbons in diesel and jet fuels. The liquid organic effluent from the first
      flow reactor contains monofunctional compounds, such as alcohols, ketones,
      carboxylic acids, and heterocycles, that can also be used to provide reactive
      intermediates for fine chemicals and polymers markets.

PMID- 18801971
TI  - Scilence.

PMID- 18801972
TI  - Museums. California academy practices what it preaches about sustainable living.

PMID- 18801973
TI  - Museums. Smithsonian takes the plunge with ocean exhibit.

PMID- 18801974
TI  - Ecology. Privatization prevents collapse of fish stocks, global analysis shows.

PMID- 18801975
TI  - Earth monitoring. Troubled U.S. satellite program runs into additional hurdles.

PMID- 18801976
TI  - Epidemiology. Lower malaria numbers reflect better estimates and a glimmer of
      hope.

PMID- 18801977
TI  - Scholarly publishing. House weighs proposal to block mandatory 'Open Access'.

PMID- 18801978
TI  - Science education. And then there was one.

PMID- 18801979
TI  - Agricultural research. Australia's new era for GM crops.

PMID- 18801980
TI  - Tailoring AIDS prevention.

PMID- 18801981
TI  - HIV testing for whole populations.

PMID- 18801982
TI  - Effects of expanded mosquito range.

PMID- 18801983
TI  - Comment on "Age and evolution of the Grand Canyon revealed by U-Pb dating of
      water table-type speleothems".
AB  - Polyak et al. (Reports, 7 March 2008, p. 1377) reported speleothem data leading
      to their inference that the western Grand Canyon incised much earlier than
      previously thought. This contradicts several lines of published geological
      knowledge in the region, hinges upon unjustified hydrogeological assumptions, and
      is based on two anomalous data points for which we offer alternative
      explanations.

PMID- 18801984
TI  - Comment on "Age and evolution of the Grand Canyon revealed by U-Pb dating of
      water table-type speleothems".
AB  - Polyak et al. (Reports, 7 March 2008, p. 1377) reported that development of the
      western Grand Canyon began about 17 million years ago. However, their conclusion
      is based on an inappropriate conflation of Plio-Quaternary incision rates and
      longer-term rates derived from sites outside the Grand Canyon. Water-table
      declines at these sites were more likely related to local base-level changes and
      Miocene regional extensional tectonics.

PMID- 18801985
TI  - Environmental economics. Development and conservation goals in World Bank
      projects.

PMID- 18801986
TI  - Computer science. Weaving a Web of trust.

PMID- 18801987
TI  - Developmental biology. Apoptosis turbocharges epithelial morphogenesis.

PMID- 18801988
TI  - Climate change. Illuminating the modern dance of climate and CO2.

PMID- 18801990
TI  - Chemistry. Fluorous tags unstick messy chemical biology problems.

PMID- 18801989
TI  - Microbiology. Desperately seeking new antibiotics.

PMID- 18801991
TI  - Ancient permafrost and a future, warmer Arctic.
AB  - Climate models predict extensive and severe degradation of permafrost in response
      to global warming, with a potential for release of large volumes of stored
      carbon. However, the accuracy of these models is difficult to evaluate because
      little is known of the history of permafrost and its response to past warm
      intervals of climate. We report the presence of relict ground ice in subarctic
      Canada that is greater than 700,000 years old, with the implication that ground
      ice in this area has survived past interglaciations that were warmer and of
      longer duration than the present interglaciation.

PMID- 18801992
TI  - Shape changes of supported Rh nanoparticles during oxidation and reduction
      cycles.
AB  - The microscopic insight into how and why catalytically active nanoparticles
      change their shape during oxidation and reduction reactions is a pivotal
      challenge in the fundamental understanding of heterogeneous catalysis. We report
      an oxygen-induced shape transformation of rhodium nanoparticles on magnesium
      oxide (001) substrates that is lifted upon carbon monoxide exposure at 600
      kelvin. A Wulff analysis of high-resolution in situ x-ray diffraction, combined
      with transmission electron microscopy, shows that this phenomenon is driven by
      the formation of a oxygen-rhodium-oxygen surface oxide at the rhodium nanofacets.
      This experimental access into the behavior of such nanoparticles during a
      catalytic cycle is useful for the development of improved heterogeneous
      catalysts.

PMID- 18801993
TI  - 4D electron diffraction reveals correlated unidirectional behavior in zinc oxide
      nanowires.
AB  - The confined electronic structure of nanoscale materials has increasingly been
      shown to induce behavior quite distinct from that of bulk analogs. Direct atomic
      scale visualization of nanowires of zinc oxide was achieved through their unique
      pancake-type diffraction by using four-dimensional (4D) ultrafast electron
      crystallography. After electronic excitation of this wide-gap photonic material,
      the wires were found to exhibit colossal expansions, two orders of magnitude
      higher than that expected at thermal equilibrium; the expansion is highly
      anisotropic, a quasi-one-dimensional behavior, and is facilitated by the induced
      antibonding character. By reducing the density of nanowires, the expansions reach
      even larger values and occur at shorter times, suggesting a decrease of the
      structural constraint in transient atomic motions. This unanticipated ultrafast
      carrier-driven expansion highlights the optoelectronic consequences of nanoscale
      morphologies.

PMID- 18801994
TI  - Chondrulelike objects in short-period comet 81P/Wild 2.
AB  - The Stardust spacecraft returned cometary samples that contain crystalline
      material, but the origin of the material is not yet well understood. We found
      four crystalline particles from comet 81P/Wild 2 that were apparently formed by
      flash-melting at a high temperature and are texturally, mineralogically, and
      compositionally similar to chondrules. Chondrules are submillimeter particles
      that dominate chondrites and are believed to have formed in the inner solar
      nebula. The comet particles show oxygen isotope compositions similar to
      chondrules in carbonaceous chondrites that compose the middle-to-outer asteroid
      belt. The presence of the chondrulelike objects in the comet suggests that
      chondrules have been transported out to the cold outer solar nebula and spread
      widely over the early solar system.

PMID- 18801995
TI  - Political attitudes vary with physiological traits.
AB  - Although political views have been thought to arise largely from individuals'
      experiences, recent research suggests that they may have a biological basis. We
      present evidence that variations in political attitudes correlate with
      physiological traits. In a group of 46 adult participants with strong political
      beliefs, individuals with measurably lower physical sensitivities to sudden
      noises and threatening visual images were more likely to support foreign aid,
      liberal immigration policies, pacifism, and gun control, whereas individuals
      displaying measurably higher physiological reactions to those same stimuli were
      more likely to favor defense spending, capital punishment, patriotism, and the
      Iraq War. Thus, the degree to which individuals are physiologically responsive to
      threat appears to indicate the degree to which they advocate policies that
      protect the existing social structure from both external (outgroup) and internal
      (norm-violator) threats.

PMID- 18801996
TI  - An alternative menaquinone biosynthetic pathway operating in microorganisms.
AB  - In microorganisms, menaquinone is an obligatory component of the electron
      transfer pathway. It is derived from chorismate by seven enzymes in Escherichia
      coli. However, a bioinformatic analysis of whole genome sequences has suggested
      that some microorganisms, including pathogenic species such as Helicobacter
      pylori and Campylobacter jejuni, do not have orthologs of the men genes, even
      though they synthesize menaquinone. We deduced the outline of this alternative
      pathway in a nonpathogenic strain of Streptomyces by bioinformatic screening,
      gene knockouts, shotgun cloning with isolated mutants, and in vitro studies with
      recombinant enzymes. As humans and commensal intestinal bacteria, including
      lactobacilli, lack this pathway, it represents an attractive target for the
      development of chemotherapeutics.

PMID- 18801997
TI  - An inhibitor of FtsZ with potent and selective anti-staphylococcal activity.
AB  - FtsZ is an essential bacterial guanosine triphosphatase and homolog of mammalian
      beta-tubulin that polymerizes and assembles into a ring to initiate cell
      division. We have created a class of small synthetic antibacterials, exemplified
      by PC190723, which inhibits FtsZ and prevents cell division. PC190723 has potent
      and selective in vitro bactericidal activity against staphylococci, including
      methicillin- and multi-drug-resistant Staphylococcus aureus. The putative
      inhibitor-binding site of PC190723 was mapped to a region of FtsZ that is
      analogous to the Taxol-binding site of tubulin. PC190723 was efficacious in an in
      vivo model of infection, curing mice infected with a lethal dose of S. aureus.
      The data validate FtsZ as a target for antibacterial intervention and identify
      PC190723 as suitable for optimization into a new anti-staphylococcal therapy.

PMID- 18801998
TI  - Suppression of cotton bollworm in multiple crops in China in areas with Bt toxin
      containing cotton.
AB  - Transgenic cotton that has been engineered to produce insecticidal toxins from
      Bacillus thuringiensis (Bt) and so to resist the pest cotton bollworm
      (Helicoverpa armigera) has been widely planted in Asia. Analysis of the
      population dynamics of H. armigera from 1992 to 2007 in China indicated that a
      marked decrease in regional outbreaks of this pest in multiple crops was
      associated with the planting of Bt cotton. The study area included six provinces
      in northern China with an annual total of 3 million hectares of cotton and 22
      million hectares of other crops (corn, peanuts, soybeans, and vegetables) grown
      by more than 10 million resource-poor farmers. Our data suggest that Bt cotton
      not only controls H. armigera on transgenic cotton designed to resist this pest
      but also may reduce its presence on other host crops and may decrease the need
      for insecticide sprays in general.

PMID- 18801999
TI  - Can catch shares prevent fisheries collapse?
AB  - Recent reports suggest that most of the world's commercial fisheries could
      collapse within decades. Although poor fisheries governance is often implicated,
      evaluation of solutions remains rare. Bioeconomic theory and case studies suggest
      that rights-based catch shares can provide individual incentives for sustainable
      harvest that is less prone to collapse. To test whether catch-share fishery
      reforms achieve these hypothetical benefits, we have compiled a global database
      of fisheries institutions and catch statistics in 11,135 fisheries from 1950 to
      2003. Implementation of catch shares halts, and even reverses, the global trend
      toward widespread collapse. Institutional change has the potential for greatly
      altering the future of global fisheries.

PMID- 18802000
TI  - Apoptotic force and tissue dynamics during Drosophila embryogenesis.
AB  - Understanding cell morphogenesis during metazoan development requires knowledge
      of how cells and the extracellular matrix produce and respond to forces. We
      investigated how apoptosis, which remodels tissue by eliminating supernumerary
      cells, also contributes forces to a tissue (the amnioserosa) that promotes cell
      sheet fusion (dorsal closure) in the Drosophila embryo. We showed that expression
      in the amnioserosa of proteins that suppress or enhance apoptosis slows or speeds
      dorsal closure, respectively. These changes correlate with the forces produced by
      the amnioserosa and the rate of seam formation between the cell sheets (zipping),
      key processes that contribute to closure. This apoptotic force is used by the
      embryo to drive cell-sheet movements during development, a role not classically
      attributed to apoptosis.

PMID- 18802001
TI  - Clusters of hyperactive neurons near amyloid plaques in a mouse model of
      Alzheimer's disease.
AB  - The neurodegeneration observed in Alzheimer's disease has been associated with
      synaptic dismantling and progressive decrease in neuronal activity. We tested
      this hypothesis in vivo by using two-photon Ca2+ imaging in a mouse model of
      Alzheimer's disease. Although a decrease in neuronal activity was seen in 29% of
      layer 2/3 cortical neurons, 21% of neurons displayed an unexpected increase in
      the frequency of spontaneous Ca2+ transients. These "hyperactive" neurons were
      found exclusively near the plaques of amyloid beta-depositing mice. The
      hyperactivity appeared to be due to a relative decrease in synaptic inhibition.
      Thus, we suggest that a redistribution of synaptic drive between silent and
      hyperactive neurons, rather than an overall decrease in synaptic activity,
      provides a mechanism for the disturbed cortical function in Alzheimer's disease.

PMID- 18802002
TI  - Reward-predictive cues enhance excitatory synaptic strength onto midbrain
      dopamine neurons.
AB  - Using sensory information for the prediction of future events is essential for
      survival. Midbrain dopamine neurons are activated by environmental cues that
      predict rewards, but the cellular mechanisms that underlie this phenomenon remain
      elusive. We used in vivo voltammetry and in vitro patch-clamp electrophysiology
      to show that both dopamine release to reward predictive cues and enhanced
      synaptic strength onto dopamine neurons develop over the course of cue-reward
      learning. Increased synaptic strength was not observed after stable behavioral
      responding. Thus, enhanced synaptic strength onto dopamine neurons may act to
      facilitate the transformation of neutral environmental stimuli to salient reward
      predictive cues.

PMID- 18802003
TI  - Molecular coupling of Xist regulation and pluripotency.
AB  - During mouse embryogenesis, reversion of imprinted X chromosome inactivation in
      the pluripotent inner cell mass of the female blastocyst is initiated by the
      repression of Xist from the paternal X chromosome. Here we report that key
      factors supporting pluripotency-Nanog, Oct3/4, and Sox2-bind within Xist intron 1
      in undifferentiated embryonic stem (ES) cells. Whereas Nanog null ES cells
      display a reversible and moderate up-regulation of Xist in the absence of any
      apparent modification of Oct3/4 and Sox2 binding, the drastic release of all
      three factors from Xist intron 1 triggers rapid ectopic accumulation of Xist RNA.
      We conclude that the three main genetic factors underlying pluripotency cooperate
      to repress Xist and thus couple X inactivation reprogramming to the control of
      pluripotency during embryogenesis.

PMID- 18802005
TI  - Essential role of Rap signal in pre-TCR-mediated beta-selection checkpoint in
      alphabeta T-cell development.
AB  - We demonstrate that lck promoter-driven conditional expression of transgenic SPA
      1, a Rap GTPase-activation protein, causes a profound defect of alphabeta T-cell
      development at the CD4/CD8 double-negative (DN) stage due to enhanced cell death
      without affecting gammadelta T-cell development. The effect was specific to the
      DN stage, because CD4 promoter-driven SPA-1 expression hardly affected T-cell
      development. Rap1A17, a dominant-negative Rap mutant, interfered with the
      generation of double-positive (DP) cells from Rag2(-/-) fetal thymocytes in vitro
      in the presence of anti-CD3epsilon antibody and Notch ligand. Rap GTPases were
      activated in a DN cell line by the expression of self-oligomerizing CD3
      (CD8:CD3epsilon chimera), which substituted autonomous pre-T-cell receptor (TCR)
      signal, inducing CD69 expression and CD25 down-regulation. Reciprocally,
      expression of C3G, a Rap guanine nucleotide exchange factor, in both normal and
      Rag2(-/-) DN cells markedly enhanced Notch-dependent generation and expansion of
      DP cells without additional anti-CD3epsilon antibody, thus bypassing pre-TCR.
      Defective alphabeta T-cell development in the conditional SPA-1-transgenic mice
      was restored completely by introducing a p53(-/-) mutation. These results suggest
      that endogenous Rap GTPases downstream of pre-TCR play an essential role in
      rescuing pre-T cells from the p53-mediated checkpoint response, thus allowing
      Notch-mediated expansion and differentiation.

PMID- 18802006
TI  - Induction of CD4+ T-cell anergy and apoptosis by activated human B cells.
AB  - B cells are well-known mediators of humoral immunity and serve as costimulators
      in the generation of T cell-mediated responses. In several mouse models, however,
      it was observed that B cells can also down-regulate immune reactions, suggesting
      a dual role for B cells. Due to this discrepancy and so far limited data, we
      directly tested the effects of primary human B cells on activated CD4(+) T helper
      cells in vitro. We found that under optimal costimulation large, activated
      CD25(+) B cells but not small CD25(-) B cells induced temporary T-cell anergy,
      determined by cell division arrest and down-regulation of cytokine production. In
      addition, large CD25(+) B cells directly induced CD95-independent apoptosis in a
      subpopulation of activated T cells. Suppression required direct B-T-cell contact
      and was not transferable from T to T cell, excluding potential involvement of
      regulatory T cells. Moreover, inhibitory effects involved an IL-2-dependent
      mechanism, since decreasing concentrations of IL-2 led to a shift from inhibitory
      toward costimulatory effects triggered by B cells. We conclude that activated
      CD25(+) B cells are able to costimulate or down-regulate T-cell responses,
      depending on activation status and environmental conditions that might also
      influence their pathophysiological impact.

PMID- 18802007
TI  - SWAP-70 regulates RhoA/RhoB-dependent MHCII surface localization in dendritic
      cells.
AB  - Stimulated dendritic cells (DCs) mature and migrate to lymphoid organs to prime
      naive T cells. DC maturation augments antigen-presentation capacity of DCs by
      increasing peptide loading, half-life, and cell surface localization of MHC
      molecules. Activated SWAP-70(-/-) DCs fail to properly localize MHCII molecules
      in the plasma membrane, are strongly impaired in T-cell activation, and are
      altered in F-actin rearrangement. MHCII synthesis, invariant chain removal, and
      MHCII internalization, however, are unaffected. MHCII surface localization is
      known to require RhoGTPases. Surprisingly, SWAP70, hitherto known to bind F-actin
      and Rac, also binds RhoA-GTP. In SWAP-70(-/-) DCs, RhoA and RhoB are stimulus
      independent and constitutively active. Surface localization of MHCII molecules
      and T-cell activation can be restored by blocking RhoA and RhoB before but not
      during DC activation. Thus, contrasting positive regulation of Rac, SWAP-70
      negatively regulates RhoA and-indirectly-RhoB, preventing premature RhoA/RhoB
      activation. Through RhoA/RhoB regulation, SWAP-70 defines a new pathway to
      control surface localization of MHCII, a critical element in DC-dependent immune
      responses.

PMID- 18802008
TI  - Megakaryocyte-derived microparticles: direct visualization and distinction from
      platelet-derived microparticles.
AB  - Platelet microparticles are a normal constituent of circulating blood. Several
      studies have demonstrated positive correlations between thrombotic states and
      platelet microparticle levels. Yet little is known about the processes by which
      platelet microparticles are generated in vivo. We now characterize microparticles
      derived directly from megakaryocytes. Video microscopy of live mouse
      megakaryocytes demonstrated that microparticles form as submicron beads along the
      lengths of slender, unbranched micropodia. These microparticles are CD41(+),
      CD42b(+), and express surface phosphatidylserine. Megakaryocyte microparticle
      generation is resistant to inhibition of microtubule assembly, which is critical
      to platelet formation, and augmented by inhibition of actin polymerization. To
      determine whether circulating microparticles are derived primarily from activated
      platelets or megakaryocytes, we identified markers that distinguish between these
      2 populations. CD62P and LAMP-1 were found only on mouse microparticles from
      activated platelets. In contrast, full-length filamin A was found in
      megakaryocyte-derived microparticles, but not microparticles from activated
      platelets. Circulating microparticles isolated from mice were CD62P(-), LAMP-1(-)
      and expressed full-length filamin A, indicating a megakaryocytic origin.
      Similarly, circulating microparticles isolated from healthy volunteers were
      CD62P(-) and expressed full-length filamin A. Cultured human megakaryocytes
      elaborated microparticles that were CD41(+), CD42b(+), and express surface
      phosphatidylserine. These results indicate that direct production by
      megakaryocytes represents a physiologic means to generate circulating platelet
      microparticles.

PMID- 18802010
TI  - Primary lymphoma of the central nervous system: just DLBCL or not?

PMID- 18802009
TI  - Estrogen inhibits dendritic cell maturation to RNA viruses.
AB  - Dendritic cells (DCs) play a central role in initiating and polarizing the immune
      response. Therefore, DC maturation represents a key control point in the shift
      from innate to adaptive immunity. It is suspected that during pregnancy, hormones
      are critical factors that modulate changes reported to occur in maternal
      immunity. Here we examined the effect of 17-beta-estradiol (E2) on the
      maturational response triggered by virus in human DCs and its influence on their
      ability to activate naive T cells. We developed an in vitro system to measure the
      response of DCs to virus infection with Newcastle disease virus (NDV) after a 24
      hour E2 treatment. Using this system, we demonstrated that E2 pretreatment down
      regulated the antiviral response to RNA viruses in DCs by profoundly suppressing
      type I interferon (IFN) synthesis and other important inflammatory products. In
      addition, the DCs capacity to stimulate naive CD4 T cells was also reduced. These
      results suggest an important role for E2 in suppressing the antiviral response
      and provide a mechanism for the reduced immunity to virus infection observed
      during pregnancy.

PMID- 18802011
TI  - Anti-inflammatory effects of an inflammatory chemokine: CCL2 inhibits lymphocyte
      homing by modulation of CCL21-triggered integrin-mediated adhesions.
AB  - Our studies focus on the pathways that restrict homing of specific subsets of
      immune cells, and thereby fine-tune the immune response at specific lymphoid and
      peripheral tissues. Here, we report that CCL2 (at picomolar [pM] levels) renders
      both murine and human T cells defective in their ability to develop CCR7
      triggered activation of LFA-1- and LFA-1-mediated adhesion strengthening to
      endothelial ICAM-1 both in vitro and in vivo. CCL2 also attenuated lymphocyte
      chemotaxis toward lymph node chemokines. Consequently, low-dose CCL2 inhibited
      lymphocyte homing to peripheral lymph nodes but did not affect lymphocyte
      trafficking through the spleen. Impaired homing of lymphocytes to peripheral
      lymph nodes resulted in attenuated progression of both asthma and adjuvant
      arthritis. Thus, pM levels of circulating CCL2 can exert global suppressive
      effects on T-cell trafficking and differentiation within peripheral lymph nodes,
      and may be clinically beneficial as an anti-inflammatory agent.

PMID- 18802012
TI  - Contribution of bone marrow-derived cells associated with brain angiogenesis is
      primarily through leukocytes and macrophages.
AB  - OBJECTIVE: We investigated the role of bone marrow-derived cells (BMDCs) in an
      angiogenic focus, induced by VEGF stimulation. METHODS AND RESULTS: BM from GFP
      donor mice was isolated and transplanted into lethally irradiated recipients.
      Four weeks after transplantation, groups of mice received adeno-associated viral
      vector (AAV)-VEGF or AAV-lacZ gene (control) injection and were euthanized at 1
      to 24 weeks. BMDCs were characterized by double-labeled immunostaining. The
      function of BMDCs was further examined through matrix metalloproteinase (MMP)-2
      and -9 activity. We found that capillary density increased after 2 weeks, peaked
      at 4 weeks (P<0.01), and sustained up to 24 weeks after gene transfer. GFP
      positive BMDCs infiltration in the angiogenic focus began at 1 week, peaked at 2
      weeks, and decreased thereafter. The GFP-positive BMDCs were colocalized with
      CD45 (94%), CD68 (71%), 5% Vimentin (5%), CD31/von Willebrand factor (vWF) (1%),
      and alpha-smooth muscle actin (alpha -SMA, 0.5%). Infiltrated BMDCs expressed MMP
      9. MMP-9 KO mice confirmed the dependence of the angiogenic response on MMP-9
      availability. CONCLUSIONS: Nearly all BMDCs in the angiogenic focus showed
      expression for leukocytes/macrophages, indicating that BMDCs minimally
      incorporated into the neovasculature. Colocalization of MMPs with GFP suggests
      that BMDCs play a critical role in VEGF-induced angiogenic response through up
      regulation of MMPs.

PMID- 18802013
TI  - Inhibition of tumor necrosis factor alpha-stimulated monocyte adhesion to human
      aortic endothelial cells by AMP-activated protein kinase.
AB  - OBJECTIVE: Proatherosclerotic adhesion of leukocytes to the endothelium is
      attenuated by NO. As AMP-activated protein kinase (AMPK) regulates endothelial NO
      synthesis, we investigated the modulation of adhesion to cultured human aortic
      endothelial cells (HAECs) by AMPK. METHODS AND RESULTS: HAECs incubated with the
      AMPK activator, AICAR, or expressing constitutively active AMPK demonstrated
      reduced TNFalpha-stimulated adhesion of promonocytic U-937 cells. Rapid
      inhibition of TNFalpha-stimulated U-937 cell adhesion by AICAR was NO-dependent,
      associated with unaltered cell surface adhesion molecule expression, and reduced
      MCP-1 secretion by HAECs. In contrast, inhibition of TNFalpha-stimulated U-937
      cell adhesion by prolonged AMPK activation was NO-independent and associated with
      reduced cell surface adhesion molecule expression. CONCLUSIONS: AMPK activation
      in HAECs inhibits TNFalpha-stimulated leukocyte adhesion by a rapid NO-dependent
      mechanism associated with reduced MCP-1 secretion and a late NO-independent
      mechanism whereby adhesion molecule expression, in particular E-selectin, is
      suppressed.

PMID- 18802015
TI  - Intramuscular administration of AAV1-lipoprotein lipase S447X lowers
      triglycerides in lipoprotein lipase-deficient patients.

PMID- 18802014
TI  - Differential role of von Willebrand factor and P-selectin on microvascular
      thrombosis in endotoxemia.
AB  - OBJECTIVE: Endotoxin (lipopolysaccharide [LPS]) enhances microvascular thrombosis
      in mouse cremaster venules. Because von Willebrand factor (vWF) and P-selectin
      are suggested to mediate LPS-induced platelet-microvessel interactions, we
      determined whether vWF and P-selectin contribute to microvascular thrombosis in
      endotoxemia. METHODS AND RESULTS: A light/dye-induced thrombosis model was used
      in cremaster microvessels of saline or LPS-injected mice (wild-type, P-selectin
      deficient, vWF-deficient, or littermate controls). In each strain except vWF
      deficient mice, LPS enhanced thrombosis in venules, resulting in approximately
      30% to 55% reduction in times to thrombotic occlusion. LPS had no effect on
      thrombosis in vWF-deficient mice, although these mice had similar systemic
      responses to LPS (tachycardia, thrombocytopenia, and plasma coagulation markers).
      vWF-deficient mice demonstrated prolonged times to thrombotic occlusion relative
      to littermates. LPS increased plasma vWF in each strain studied. While
      immunofluorescence in wild-type mice failed to detect LPS-induced differences in
      microvascular vWF expression, it revealed markedly higher vWF expression in
      venules relative to arterioles. CONCLUSIONS: vWF mediates light/dye-induced
      microvascular thrombosis and endotoxin-induced enhancement of thrombosis in mouse
      cremaster venules; P-selectin is not required for enhanced thrombosis in response
      to endotoxin. Enhanced vWF expression in venules relative to arterioles has
      potential implications for the differences in thrombotic responses among these
      microvessels.

PMID- 18802016
TI  - Molecular mechanisms of atherosclerosis in metabolic syndrome: role of reduced
      IRS2-dependent signaling.
AB  - OBJECTIVE: The mechanisms underlying accelerated atherosclerosis in metabolic
      syndrome (MetS) patients remain poorly defined. In the mouse, complete disruption
      of insulin receptor substrate-2 (Irs2) causes insulin resistance, MetS-like
      manifestations, and accelerates atherosclerosis. Here, we performed human, mouse,
      and cell culture studies to gain insight into the contribution of defective Irs2
      signaling to MetS-associated alterations. METHODS AND RESULTS: In circulating
      leukocytes from insulin-resistant MetS patients, Irs2 and Akt2 mRNA levels
      inversely correlate with plasma insulin levels and HOMA index and are reduced
      compared to insulin-sensitive MetS patients. Notably, a moderate reduction in
      Irs2 expression in fat-fed apolipoprotein E-null mice lacking one allele of Irs2
      (apoE(-/-)Irs2(+/-)) accelerates atherosclerosis compared to apoE-null controls,
      without affecting plaque composition. Partial Irs2 inactivation also increases
      CD36 and SRA scavenger receptor expression and modified LDL uptake in
      macrophages, diminishes Akt2 and Ras expression in aorta, and enhances expression
      of the proatherogenic cytokine MCP1 in aorta and primary vascular smooth muscle
      cells (VSMCs) and macrophages. Inhibition of AKT or ERK1/2, a downstream target
      of RAS, upregulates Mcp1 in VSMCs. CONCLUSIONS: Enhanced levels of MCP1 resulting
      from reduced IRS2 expression and accompanying defects in AKT2 and Ras/ERK1/2
      signaling pathways may contribute to accelerated atherosclerosis in MetS states.

PMID- 18802017
TI  - Liver X receptor activation induces the uptake of cholesteryl esters from high
      density lipoproteins in primary human macrophages.
AB  - OBJECTIVE: Liver X receptors (LXRs) are oxysterol-activated nuclear receptors
      regulating reverse cholesterol transport, in part by modulating cholesterol
      efflux from macrophages to apoAI and HDL via the ABCA1 and ABCG1/ABCG4 pathways.
      Moreover, LXR activation increases intracellular cholesterol trafficking via the
      induction of NPC1 and NPC2 expression. However, implication of LXRs in the
      selective uptake of cholesteryl esters from lipoproteins in human macrophages has
      never been reported. METHODS AND RESULTS: Our results show that (1) selective CE
      uptake from HDL(3) is highly efficient in human monocyte-derived macrophages; (2)
      surprisingly, HDL(3)-CE uptake is strongly increased by LXR activation despite
      antiatherogenic effects of LXRs; (3) HDL(3)-CE uptake increase is not linked to
      SR-BI expression modulation but it is dependent of proteoglycan interactions; (4)
      HDL(3)-CE uptake increase is associated with increased expression and secretion
      of apoE and LPL, two proteins interacting with proteoglycans; (5) HDL(3)-CE
      uptake increase depends on the integrity of raft domains and is associated with
      an increased caveolin-1 expression. CONCLUSIONS: Our study identifies a new role
      for LXRs in the control of cholesterol homeostasis in human macrophages. LXR
      activation results in enhanced dynamic intracellular cholesterol fluxes through
      an increased CE uptake from HDL and leads to an increased cholesterol
      availability to efflux to apoAI and HDL.

PMID- 18802018
TI  - Impaired Notch4 activity elicits endothelial cell activation and apoptosis:
      implication for transplant arteriosclerosis.
AB  - OBJECTIVE: Notch signaling pathway controls key functions in vascular and
      endothelial cells (EC). However, little is known about the role of Notch in
      allografted vessels during the development of transplant arteriosclerosis (TA).
      This study investigated regulation of the Notch pathway on cardiac allograft
      arteriosclerosis and further examined its implication in EC dysfunction. METHODS
      AND RESULTS: Here we show that, among Notch receptors, Notch2, -3, and -4
      transcript levels were markedly downregulated in TA compared to tolerant and
      syngeneic allografts. TA correlates with high levels of tumor necrosis factor
      (TNF), transforming growth factor (TGF)beta, and IL10, which consistently
      decrease Notch4 expression in transplants and cultured ECs. We found that
      inhibition of Notch activity, reflected by both a reduced CBF1 activity and Hes1
      expression, parallels the downregulation of Notch4 expression mediated by TNF in
      ECs. Notch4 and Hes1 knockdown enhances vascular cell adhesion molecule-1
      expression and promotes EC apoptosis. Silencing Notch4 or Hes1 also drastically
      inhibits repair of endothelial injury. Overall, our results suggest that Notch4
      and basal Notch activity are required to maintain EC quiescence and for optimal
      survival and repair in response to injury. CONCLUSIONS: Together, our findings
      indicate that impaired Notch4 activity in graft ECs is a key event associated
      with TA by triggering EC activation and apoptosis.

PMID- 18802019
TI  - Common SNPs in HMGCR in micronesians and whites associated with LDL-cholesterol
      levels affect alternative splicing of exon13.
AB  - Background- Variation in LDL-cholesterol (LDL-C) among individuals is a complex
      genetic trait involving multiple genes and gene-environment interactions. METHODS
      AND RESULTS: In a genome-wide association study (GWAS) to identify genetic
      variants influencing LDL-C in an isolated population from Kosrae, we observed
      associations for SNPs in the gene encoding 3hydroxy-3-methylglutaryl (HMG)
      coenzyme A (CoA) reductase (HMGCR). Three of these SNPs (rs7703051, rs12654264,
      and rs3846663) met the statistical threshold of genome-wide significance when
      combined with data from the Diabetes Genetics Initiative GWAS. We followed up the
      association results and identified a functional SNP in intron13 (rs3846662),
      which was in linkage disequilibrium with the SNPs of genome-wide significance and
      affected alternative splicing of HMGCR mRNA. In vitro studies in human
      lymphoblastoid cells demonstrated that homozygosity for the rs3846662 minor
      allele was associated with up to 2.2-fold lower expression of alternatively
      spliced HMGCR mRNA lacking exon13, and minigene transfection assays confirmed
      that allele status at rs3846662 directly modulated alternative splicing of HMGCR
      exon13 (42.9+/-3.9 versus 63.7+/-1.0%Deltaexon13/total HMGCR mRNA, P=0.02).
      Further, the alternative splice variant could not restore HMGCR activity when
      expressed in HMGCR deficient UT-2 cells. CONCLUSIONS: We identified variants in
      HMGCR that are associated with LDL-C across populations and affect alternative
      splicing of HMGCR exon13.

PMID- 18802020
TI  - The role of chemokines in transplant graft arterial disease.
AB  - Despite the development of effective immunosuppressive therapy, transplant graft
      arterial disease (GAD) remains the major limitation to long-term graft survival.
      Multiple immune and nonimmune risk factors contribute to this vasculopathic
      intimal hyperplastic process. Thus, initial interplay between host inflammatory
      cells and donor endothelial cells triggers alloimmune responses, whereas
      alloantigen-independent factors such as prolonged ischemia, surgical
      manipulation, ischemia-reperfusion injury, and hyperlipidemia enhance the antigen
      dependent events. Intrinsic to all stages of this process are chemokines, a
      family of 8- to 10-kDa proteins mediating directional migration of immune cells
      to sites of inflammation and injury. Beyond their role in immune-cell chemotaxis,
      chemokines also contribute to cellular activation, vascular remodeling, and
      angiogenesis. Expression of chemokines and their cognate receptors in allografts
      correlates with acute organ rejection, as well as GAD. Moreover, chemokine or
      chemokine receptor blockade prolongs graft survival and attenuates GAD in
      experimental models. Further studies will likely confirm a substantial utility
      for antichemokine therapy in human organ transplantation.

PMID- 18802021
TI  - Isoprostanes inhibit vascular endothelial growth factor-induced endothelial cell
      migration, tube formation, and cardiac vessel sprouting in vitro, as well as
      angiogenesis in vivo via activation of the thromboxane A(2) receptor: a potential
      link between oxidative stress and impaired angiogenesis.
AB  - Isoprostanes are endogenously formed end products of lipid peroxidation.
      Furthermore, they are markers of oxidative stress and independent risk markers of
      coronary heart disease. In patients experiencing coronary heart disease, impaired
      angiogenesis may exacerbate insufficient blood supply of ischemic myocardium. We
      therefore hypothesized that isoprostanes may exert detrimental cardiovascular
      effects by inhibiting angiogenesis. We studied the effect of isoprostanes on
      vascular endothelial growth factor (VEGF)-induced migration and tube formation of
      human endothelial cells (ECs), and cardiac angiogenesis in vitro as well as on
      VEGF-induced angiogenesis in the chorioallantoic membrane assay in vivo. The
      isoprostanes 8-iso-PGF(2alpha), 8-iso-PGE(2), and 8-iso-PGA(2) inhibited VEGF
      induced migration, tube formation of ECs, and cardiac angiogenesis in vitro, as
      well as VEGF-induced angiogenesis in vivo via activation of the thromboxane A(2)
      receptor (TBXA2R): the specific TBXA2R antagonists SQ-29548, BM 567, and ICI
      192,605 but not the thromboxane A(2) synthase inhibitor ozagrel blocked the
      effect of isoprostanes. The isoprostane 8-iso-PGA(2) degraded into 2 biologically
      active derivatives in vitro, which also inhibited EC tube formation via the
      TBXA2R. Moreover, short hairpin RNA-mediated knockdown of the TBXA2R antagonized
      isoprostane-induced effects. In addition, Rho kinase inhibitor Y-27632 reversed
      the inhibitory effect of isoprostanes and the thromboxane A(2) mimetic U-46619 on
      EC migration and tube formation. Finally, the various isoprostanes exerted a
      synergistic inhibitory effect on EC tube formation. We demonstrate for the first
      time that isoprostanes inhibit angiogenesis via activation of the TBXA2R. By this
      mechanism, isoprostanes may contribute directly to exacerbation of coronary heart
      disease and to capillary rarefaction in disease states of increased oxidative
      stress.

PMID- 18802022
TI  - Interactions, functions, and independence of plasma membrane STIM1 and TRPC1 in
      vascular smooth muscle cells.
AB  - Stromal interaction molecule 1 (STIM1) is a predicted single membrane-spanning
      protein involved in store-operated calcium entry and interacting with ion
      channels including TRPC1. Here, we focus on endogenous STIM1 of modulated
      vascular smooth muscle cells, which exhibited a nonselective cationic current in
      response to store depletion despite strong buffering of intracellular calcium at
      the physiological concentration. STIM1 mRNA and protein were detected and
      suppressed by specific short interfering RNA. Calcium entry evoked by store
      depletion was partially inhibited by STIM1 short interfering RNA, whereas calcium
      release was unaffected. STIM1 short interfering RNA suppressed cell migration but
      not proliferation. Antibody that specifically bound STIM1 revealed constitutive
      extracellular N terminus of STIM1 and extracellular application of the antibody
      caused fast inhibition of the current evoked by store depletion. The antibody
      also inhibited calcium entry and cell migration but not proliferation. STIM1
      interacted with TRPC1, and TRPC1 contributed partially to calcium entry and
      cationic current. However, the underlying processes could not be explained only
      by a STIM1-TRPC1 partnership because extracellular TRPC1 antibody suppressed
      cationic current only in a fraction of cells, TRPC1-containing channels were
      important for cell proliferation as well as migration, and cell surface
      localization studies revealed TRPC1 alone, as well as with STIM1. The data
      suggest a complex situation in which there is not only plasma membrane-spanning
      STIM1 that is important for cell migration and TRPC1-independent store-operated
      cationic current but also TRPC1-STIM1 interaction, a TRPC1-dependent component of
      store-operated current, and STIM1-independent TRPC1 linked to cell proliferation.

PMID- 18802023
TI  - Vascular endothelial growth factor-A specifies formation of native collaterals
      and regulates collateral growth in ischemia.
AB  - The density of native (preexisting) collaterals and their capacity to enlarge
      into large conduit arteries in ischemia (arteriogenesis) are major determinants
      of the severity of tissue injury in occlusive disease. Mechanisms directing
      arteriogenesis remain unclear. Moreover, nothing is known about how native
      collaterals form in healthy tissue. Evidence suggests vascular endothelial growth
      factor (VEGF), which is important in embryonic vascular patterning and ischemic
      angiogenesis, may contribute to native collateral formation and arteriogenesis.
      Therefore, we examined mice heterozygous for VEGF receptor-1 (VEGFR-1(+/-)), VEGF
      receptor-2 (VEGFR-2(+/-)), and overexpressing (VEGF(hi/+)) and underexpressing
      VEGF-A (VEGF(lo/+)). Recovery from hindlimb ischemia was followed for 21 days
      after femoral artery ligation. All statements below are P<0.05. Compared to wild
      type mice, VEGFR-2(+/-) showed similar: ischemic scores, recovery of hindlimb
      perfusion, pericollateral leukocytes, collateral enlargement, and angiogenesis.
      In contrast, VEGFR-1(+/-) showed impaired: perfusion recovery, pericollateral
      leukocytes, collateral enlargement, worse ischemic scores, and comparable
      angiogenesis. Compared to wild-type mice, VEGF(lo/+) had 2-fold lower perfusion
      immediately after ligation (suggesting fewer native collaterals which was
      confirmed by angiography) and blunted recovery of perfusion. VEGF(hi/+) mice had
      3-fold greater perfusion immediately after ligation, more native collaterals, and
      improved recovery of perfusion. These differences were confirmed in the cerebral
      pial cortical circulation where, compared to VEGF(hi/+) mice, VEGF(lo/+) formed
      fewer collaterals during the perinatal period when adult density was established,
      and had 2-fold larger infarctions after middle cerebral artery ligation. Our
      findings indicate VEGF and VEGFR-1 are determinants of arteriogenesis. Moreover,
      we describe the first signaling molecule, VEGF-A, that specifies formation of
      native collaterals in healthy tissues.

PMID- 18802024
TI  - Upstream stimulatory factor is required for human angiotensinogen expression and
      differential regulation by the A-20C polymorphism.
AB  - Among naturally occurring polymorphisms in the 5' flanking region of the human
      angiotensinogen (AGT) gene, the -20 and -217 polymorphisms have the strongest
      effects on AGT regulation in AGT-expressing cells derived from liver, kidney,
      brain, and fat. These polymorphisms may affect allele-specific transcription
      factor binding, and the high-expressing alleles are both relatively common. We
      show herein that the -20C allele has higher transcriptional activity than -20A,
      and the -20A allele confers no additional transactivation potential beyond that
      of a mutated vector. Gel-shift assays show that upstream stimulatory factor
      (USF)1 and USF2 preferentially bind the -20C allele, whereas the -20A allele
      retains a low affinity USF binding site. Plasmid immunoprecipitation assays
      confirmed preferential association of USF1 with the -20C allele in transfected
      HepG2 cells. Chromatin immunoprecipitation confirmed that USF1 binds to the
      endogenous AGT -20C allele in CCF cells, the only cell line tested that carries
      the -20C allele, and to the human AGT promoter in liver and adipose tissue from
      transgenic mice. Transduction of AGT-expressing cells with short hairpin RNAs
      specifically targeting USF1 or USF2, resulted in cell- and allele-specific
      attenuation of AGT promoter activity. In vivo, knockdown of USF expression in the
      liver of transgenic mice expressing the -20C allele of AGT resulted in lower AGT
      expression, a decrease in circulating human AGT protein but no change in
      expression of GAPDH or hepatocyte nuclear factor-4alpha. We conclude that USF1
      functionally and differentially regulates AGT expression via the -20 polymorphism
      and that the differential expression exhibited by -20 can be accounted for by
      differential association with USF1.

PMID- 18802025
TI  - Glycogen synthase kinase 3 inhibition slows mitochondrial adenine nucleotide
      transport and regulates voltage-dependent anion channel phosphorylation.
AB  - Inhibition of glycogen synthase kinase (GSK)-3 reduces ischemia/reperfusion
      injury by mechanisms that involve the mitochondria. The goal of this study was to
      explore possible molecular targets and mechanistic basis of this cardioprotective
      effect. In perfused rat hearts, treatment with GSK inhibitors before ischemia
      significantly improved recovery of function. To assess the effect of GSK
      inhibitors on mitochondrial function under ischemic conditions, mitochondria were
      isolated from rat hearts perfused with GSK inhibitors and were treated with
      uncoupler or cyanide or were made anoxic. GSK inhibition slowed ATP consumption
      under these conditions, which could be attributable to inhibition of ATP entry
      into the mitochondria through the voltage-dependent anion channel (VDAC) and/or
      adenine nucleotide transporter (ANT) or to inhibition of the F(1)F(0)-ATPase. To
      determine the site of the inhibitory effect on ATP consumption, we measured the
      conversion of ADP to AMP by adenylate kinase located in the intermembrane space.
      This assay requires adenine nucleotide transport across the outer but not the
      inner mitochondrial membrane, and we found that GSK inhibitors slow AMP
      production similar to their effect on ATP consumption. This suggests that GSK
      inhibitors are acting on outer mitochondrial membrane transport. In sonicated
      mitochondria, GSK inhibition had no effect on ATP consumption or AMP production.
      In intact mitochondria, cyclosporin A had no effect, indicating that ATP
      consumption is not caused by opening of the mitochondrial permeability transition
      pore. Because GSK is a kinase, we assessed whether protein phosphorylation might
      be involved. Therefore, we performed Western blot and 1D/2D gel phosphorylation
      site analysis using phos-tag staining to indicate proteins that had decreased
      phosphorylation in hearts treated with GSK inhibitors. Liquid chromatographic
      mass spectrometric analysis revealed 1 of these proteins to be VDAC2. Taken
      together, we found that GSK-mediated signaling modulates transport through the
      outer membrane of the mitochondria. Both proteomics and adenine nucleotide
      transport data suggest that GSK regulates VDAC and that VDAC may be an important
      regulatory site in ischemia/reperfusion injury.

PMID- 18802026
TI  - Acceleration of crossbridge kinetics by protein kinase A phosphorylation of
      cardiac myosin binding protein C modulates cardiac function.
AB  - Normal cardiac function requires dynamic modulation of contraction. beta1
      adrenergic-induced protein kinase (PK)A phosphorylation of cardiac myosin binding
      protein (cMyBP)-C may regulate crossbridge kinetics to modulate contraction. We
      tested this idea with mechanical measurements and echocardiography in a mouse
      model lacking 3 PKA sites on cMyBP-C, ie, cMyBP-C(t3SA). We developed the model
      by transgenic expression of mutant cMyBP-C with Ser-to-Ala mutations on the cMyBP
      C knockout background. Western blots, immunofluorescence, and in vitro
      phosphorylation combined to show that non-PKA-phosphorylatable cMyBP-C expressed
      at 74% compared to normal wild-type (WT) and was correctly positioned in the
      sarcomeres. Similar expression of WT cMyBP-C at 72% served as control, ie, cMyBP
      C(tWT). Skinned myocardium responded to stretch with an immediate increase in
      force, followed by a transient relaxation of force and finally a delayed
      development of force, ie, stretch activation. The rate constants of relaxation,
      k(rel) (s-1), and delayed force development, k(df) (s-1), in the stretch
      activation response are indicators of crossbridge cycling kinetics. cMyBP-C(t3SA)
      myocardium had baseline k(rel) and k(df) similar to WT myocardium, but, unlike
      WT, k(rel) and k(df) were not accelerated by PKA treatment. Reduced dobutamine
      augmentation of systolic function in cMyBP-C(t3SA) hearts during echocardiography
      corroborated the stretch activation findings. Furthermore, cMyBP-C(t3SA) hearts
      exhibited basal echocardiographic findings of systolic dysfunction, diastolic
      dysfunction, and hypertrophy. Conversely, cMyBP-C(tWT) hearts performed similar
      to WT. Thus, PKA phosphorylation of cMyBP-C accelerates crossbridge kinetics and
      loss of this regulation leads to cardiac dysfunction.

PMID- 18802027
TI  - Scleraxis is required for cell lineage differentiation and extracellular matrix
      remodeling during murine heart valve formation in vivo.
AB  - Heart valve structures, derived from mesenchyme precursor cells, are composed of
      differentiated cell types and extracellular matrix arranged to facilitate valve
      function. Scleraxis (scx) is a transcription factor required for tendon cell
      differentiation and matrix organization. This study identified high levels of scx
      expression in remodeling heart valve structures at embryonic day 15.5 through
      postnatal stages using scx-GFP reporter mice and determined the in vivo function
      using mice null for scx. Scx(-/-) mice display significantly thickened heart
      valve structures from embryonic day 17.5, and valves from mutant mice show
      alterations in valve precursor cell differentiation and matrix organization. This
      is indicated by decreased expression of the tendon-related collagen type XIV,
      increased expression of cartilage-associated genes including sox9, as well as
      persistent expression of mesenchyme cell markers including msx1 and snai1. In
      addition, ultrastructure analysis reveals disarray of extracellular matrix and
      collagen fiber organization within the valve leaflet. Thickened valve structures
      and increased expression of matrix remodeling genes characteristic of human heart
      valve disease are observed in juvenile scx(-/-) mice. In addition, excessive
      collagen deposition in annular structures within the atrioventricular junction is
      observed. Collectively, our studies have identified an in vivo requirement for
      scx during valvulogenesis and demonstrate its role in cell lineage
      differentiation and matrix distribution in remodeling valve structures.

PMID- 18802028
TI  - Nuclear alpha1-adrenergic receptors signal activated ERK localization to caveolae
      in adult cardiac myocytes.
AB  - We previously identified an alpha1-AR-ERK (alpha1A-adrenergic receptor
      extracellular signal-regulated kinase) survival signaling pathway in adult
      cardiac myocytes. Here, we investigated localization of alpha1-AR subtypes
      (alpha1A and alpha1B) and how their localization influences alpha1-AR signaling
      in cardiac myocytes. Using binding assays on myocyte subcellular fractions or a
      fluorescent alpha1-AR antagonist, we localized endogenous alpha1-ARs to the
      nucleus in wild-type adult cardiac myocytes. To clarify alpha1 subtype
      localization, we reconstituted alpha1 signaling in cultured alpha1A- and alpha1B
      AR double knockout cardiac myocytes using alpha1-AR-green fluorescent protein
      (GFP) fusion proteins. Similar to endogenous alpha1-ARs and alpha1A- and alpha1B
      GFP colocalized with LAP2 at the nuclear membrane. alpha1-AR nuclear localization
      was confirmed in vivo using alpha1-AR-GFP transgenic mice. The alpha1-signaling
      partners Galphaq and phospholipase Cbeta1 also colocalized with alpha1-ARs only
      at the nuclear membrane. Furthermore, we observed rapid catecholamine uptake
      mediated by norepinephrine-uptake-2 and found that alpha1-mediated activation of
      ERK was not inhibited by a membrane impermeant alpha1-blocker, suggesting alpha1
      signaling is initiated at the nucleus. Contrary to prior studies, we did not
      observe alpha1-AR localization to caveolae, but we found that alpha1-AR signaling
      initiated at the nucleus led to activated ERK localized to caveolae. In summary,
      our results show that nuclear alpha1-ARs transduce signals to caveolae at the
      plasma membrane in cardiac myocytes.

PMID- 18802029
TI  - Disruption of sarcolemmal ATP-sensitive potassium channel activity impairs the
      cardiac response to systolic overload.
AB  - Sarcolemmal ATP-sensitive potassium channels (K(ATP)) act as metabolic sensors
      that facilitate adaptation of the left ventricle to changes in energy
      requirements. This study examined the mechanism by which K(ATP) dysfunction
      impairs the left ventricular response to stress using transgenic mouse strains
      with cardiac-specific disruption of K(ATP) activity (SUR1-tg mice) or Kir6.2 gene
      deficiency (Kir6.2 KO). Both SUR1-tg and Kir6.2 KO mice had normal left
      ventricular mass and function under unstressed conditions. Following chronic
      transverse aortic constriction, both SUR1-tg and Kir6.2 KO mice developed more
      severe left ventricular hypertrophy and dysfunction as compared with their
      corresponding WT controls. Both SUR1-tg and Kir6.2 KO mice had significantly
      decreased expression of peroxisome proliferator-activated receptor gamma
      coactivator (PGC)-1alpha and a group of energy metabolism related genes at both
      protein and mRNA levels. Furthermore, disruption of K(ATP) repressed expression
      and promoter activity of PGC-1alpha in cultured rat neonatal cardiac myocytes in
      response to hypoxia, indicating that K(ATP) activity is required to maintain PGC
      1alpha expression under stress conditions. PGC-1alpha gene deficiency also
      exacerbated chronic transverse aortic constriction-induced ventricular
      hypertrophy and dysfunction, suggesting that depletion of PGC-1alpha can worsen
      systolic overload induced ventricular dysfunction. Both SUR1-tg and Kir6.2 KO
      mice had decreased FOXO1 after transverse aortic constriction, in agreement with
      the reports that a decrease of FOXO1 can repress PGC-1alpha expression.
      Furthermore, inhibition of K(ATP) caused a decrease of FOXO1 associated with PGC
      1alpha promoter. These data indicate that K(ATP) channels facilitate the cardiac
      response to stress by regulating PGC-1alpha and its target genes, at least
      partially through the FOXO1 pathway.

PMID- 18802030
TI  - Characterization of the steric defense of the HIV-1 gp41 N-trimer region.
AB  - During viral entry, HIV gp41 adopts a transient conformation called the
      "prehairpin intermediate" in which a highly conserved therapeutic target, the N
      trimer, is exposed. Despite extensive discovery efforts, potent and broadly
      neutralizing antibodies that target the N-trimer are elusive. We previously
      demonstrated the N-trimer is protected by a steric block that prevents large
      proteins, such as antibodies, from accessing it. Here we further characterize the
      steric block and identify its source. To study the N-trimer steric accessibility,
      we produced two sets of C-peptide inhibitors (a potent inhibitor targeting the N
      trimer) fused to cargo proteins of increasing size facing either the virus or
      cell side of the prehairpin intermediate. Both bulky inhibitor sets show a steric
      block, but the effect is more pronounced with virus-side cargo. Additionally,
      both sets maintain their potencies in a modified entry assay that removes
      possible sources of target cell steric hindrance. These results implicate a viral
      source, likely gp120, as the primary component of the steric block. In addition,
      we studied the steric accessibility of the "pocket" region of the N-trimer, a
      highly attractive drug and vaccine target. We demonstrated a pocket-specific
      antibody, D5, is more potent as an scFv than as a full-length IgG, suggesting the
      N-trimer steric restriction extends to the pocket. This characterization will
      facilitate the design of sterically restricted antigens that mimic the steric
      environment of the N-trimer in the prehairpin intermediate and are capable of
      inducing potent and broadly neutralizing antibodies that circumvent the N-trimer
      steric block.

PMID- 18802031
TI  - American ginseng suppresses inflammation and DNA damage associated with mouse
      colitis.
AB  - Ulcerative colitis (UC) is a dynamic, idiopathic, chronic inflammatory condition
      associated with a high colon cancer risk. American ginseng has antioxidant
      properties and targets many of the players in inflammation. The aim of this study
      was to test whether American ginseng extract prevents and treats colitis. Colitis
      in mice was induced by the presence of 1% dextran sulfate sodium (DSS) in the
      drinking water or by 1% oxazolone rectally. American ginseng extract was mixed in
      the chow at levels consistent with that currently consumed by humans as a
      supplement (75 p.p.m., equivalent to 58 mg daily). To test prevention of colitis,
      American ginseng extract was given prior to colitis induction. To test treatment
      of colitis, American ginseng extract was given after the onset of colitis. In
      vitro studies were performed to examine mechanisms. Results indicate that
      American ginseng extract not only prevents but it also treats colitis. Inducible
      nitric oxide synthase and cyclooxygenase-2 (markers of inflammation) and p53
      (induced by inflammatory stress) are also downregulated by American ginseng.
      Mucosal and DNA damage associated with colitis is at least in part a result of an
      oxidative burst from overactive leukocytes. We therefore tested the hypothesis
      that American ginseng extract can inhibit leukocyte activation and subsequent
      epithelial cell DNA damage in vitro and in vivo. Results are consistent with this
      hypothesis. The use of American ginseng extract represents a novel therapeutic
      approach for the prevention and treatment of UC.

PMID- 18802032
TI  - The stem cell-associated antigen CD133 (Prominin-1) is a molecular therapeutic
      target for metastatic melanoma.
AB  - CD133 (Prominin-1) is considered the most important cancer stem cell (CSC)
      associated marker identified so far, with increased expression in the CSC
      fraction of a large variety of human malignancies, including melanoma. Here we
      investigated the effects of CD133 downregulation in vitro and in vivo in human
      metastatic melanoma. The average number of CD133 molecules on the cell surface of
      FEMX-I melanoma cells was decreased by 8.7-fold and 1.8-fold using two different
      short hairpin RNAs. Downregulation of CD133, confirmed by immunocytochemistry,
      Western blotting, microarray analysis, and reverse transcription-polymerase chain
      reaction, resulted in slower cell growth, reduced cell motility, and decreased
      capacity to form spheroids under stem cell-like growth conditions. Clonal
      analysis revealed that the reduction in growth rate was proportional to the
      extent of CD133 downregulation. Monoclonal antibodies directed against two
      different epitopes of the CD133 protein induced a specific, dose-dependent
      cytotoxic effect in FEMX-I cells. The downregulation of CD133 severely reduced
      the capacity of the cells to metastasize, particularly to the spinal cord. In the
      CD133 downregulated cells, microarray analysis revealed expression changes for
      only 143 annotated genes (76 up- and 67 downregulated). Ten of the 76 upregulated
      genes coded for Wnt inhibitors, suggesting an interaction between CD133 and the
      canonical Wnt pathway. We conclude that CD133, in addition to its role as a CSC
      marker, is an important therapeutic target for metastatic melanoma and,
      potentially, for other CD133-expressing cancer types.

PMID- 18802033
TI  - Identification of stem cells during prepubertal spermatogenesis via monitoring of
      nucleostemin promoter activity.
AB  - The nucleostemin (NS) gene encodes a nucleolar protein found at high levels in
      several types of stem cells and tumor cell lines. The function of NS is unclear
      but it may play a critical role in S-phase entry by stem/progenitor cells. Here
      we characterize NS expression in murine male germ cells. Although NS protein was
      highly expressed in the nucleoli of all primordial germ cells, only a limited
      number of gonocytes showed NS expression in neonatal testes. In adult testes, NS
      protein was expressed at high levels in the nucleoli of spermatogonia and primary
      spermatocytes but at only low levels in round spermatids. To evaluate the
      properties of cells expressing high levels of NS, we generated transgenic
      reporter mice expressing green fluorescent protein (GFP) under the control of the
      NS promoter (NS-GFP Tg mice). In adult NS-GFP Tg testes, GFP and endogenous NS
      protein expression were correlated in spermatogonia and spermatocytes but GFP was
      also ectopically expressed in elongated spermatids and sperm. In testes of NS-GFP
      Tg embryos, neonates, and 10-day-old pups, however, GFP expression closely
      coincided with endogenous NS expression in developing germ cells. In contrast to
      a previous report, our results support the existence in neonatal testes of
      spermatogonial stem cells with long-term repopulating capacity. Furthermore, our
      data show that NS expression does not correlate with cell-cycle status during
      prepuberty, and that strong NS expression is essential for the maintenance of
      germline stem cell proliferation capacity. We conclude that NS is a marker of
      undifferentiated status in the germ cell lineage during prepubertal
      spermatogenesis.

PMID- 18802034
TI  - Quantitative mass spectrometry identifies drug targets in cancer stem cell
      containing side population.
AB  - A multifaceted approach is presented as a general strategy to identify new drug
      targets in a breast cancer stem cell-containing side population. The approach we
      have utilized combines side population cell sorting and stable isotope labeling
      by amino acids in cell culture with mass spectrometry to compare and identify
      proteins with differential expression profiles between side population cells,
      know to be enriched in cancer stem cells, and nonside population cells, which are
      depleted in cancer stem cells, for two breast cancer cell lines, MCF7 and MDA
      MB231. Almost 900 proteins were quantified, and several important proteins in
      cell cycle control and differentiation were found to be upregulated in the cancer
      stem cell-containing side population. Most interestingly, a splice isoform of
      pyruvate kinase M2 as well as peroxiredoxin 6 were found to be downregulated. The
      differential levels of three of these proteins, thymosin beta4 (TB4),
      proliferation-associated protein 2G4, and SIAH-interacting protein, were
      validated using Western blot. Furthermore, functional validation provided clear
      evidence that elevated TB4 expression contributes to drug resistance in the stem
      cell population. Small interfering RNA silencing of TB4 led to a loss of
      chemoresistance in two separate breast cancer populations. These proteins likely
      contribute to resistance in the cancer stem cell-containing side population, and
      their altered expression in a tumor causes clinical resistance to chemotherapy.
      The ability to perform quantitative mass spectrometry has enabled the
      identification of a series of proteins that could serve as future therapeutic
      targets.

PMID- 18802035
TI  - Regulation of prenatal human retinal neurosphere growth and cell fate potential
      by retinal pigment epithelium and Mash1.
AB  - During development of the central nervous system, stem and progenitor cell
      proliferation and differentiation are controlled by complex inter- and
      intracellular interactions that orchestrate the precise spatiotemporal production
      of particular cell types. Within the embryonic retina, progenitor cells are
      located adjacent to the retinal pigment epithelium (RPE), which differentiates
      prior to the neurosensory retina and has the capacity to secrete a multitude of
      growth factors. We found that secreted proteinaceous factors in human prenatal
      RPE conditioned medium (RPE CM) prolonged and enhanced the growth of human
      prenatal retinal neurospheres. The growth-promoting activity of RPE CM was
      mitogen-dependent and associated with an acute increase in transcription factor
      phosphorylation. Expanded populations of RPE CM-treated retinal neurospheres
      expressed numerous neurodevelopmental and eye specification genes and markers
      characteristic of neural and retinal progenitor cells, but gradually lost the
      potential to generate neurons upon differentiation. Misexpression of Mash1
      restored the neurogenic potential of long-term cultures, yielding neurons with
      phenotypic characteristics of multiple inner retinal cell types. Thus, a novel
      combination of extrinsic and intrinsic factors was required to promote both
      progenitor cell proliferation and neuronal multipotency in human retinal
      neurosphere cultures. These results support a pro-proliferative and antiapoptotic
      role for RPE in human retinal development, reveal potential limitations of human
      retinal progenitor culture systems, and suggest a means for overcoming cell fate
      restriction in vitro.

PMID- 18802036
TI  - Bromodeoxyuridine induces senescence in neural stem and progenitor cells.
AB  - Bromodeoxyuridine (BrdU) is a halogenated pyrimidine that incorporates into newly
      synthesized DNA during the S phase. BrdU is used ubiquitously in cell birthdating
      studies and as a means of measuring the proliferative index of various cell
      populations. In the absence of secondary stressors, BrdU is thought to
      incorporate relatively benignly into replicating DNA chains. However, we report
      here that a single, low-dose pulse of BrdU exerts a profound and sustained
      antiproliferative effect in cultured murine stem and progenitor cells. This is
      accompanied by altered terminal differentiation, cell morphology, and protein
      expression consistent with the induction of senescence. There is no evidence of a
      significant increase in spontaneous cell death; however, cells are rendered
      resistant to chemically induced apoptosis. Finally, we show that a brief in vivo
      BrdU regimen reduces the proliferative potential of subsequently isolated
      subependymal zone neurosphere-forming cells. We conclude, therefore, that BrdU
      treatment induces a senescence pathway that causes a progressive decline in the
      replication of rapidly dividing stem/progenitor cells, suggesting a novel and
      uncharacterized effect of BrdU. This finding is significant in that BrdU
      incorporating neural stem/progenitor cells and their progeny should not be
      expected to behave normally with respect to proliferative potential and
      downstream functional parameters. This effect highlights the need for caution
      when results based on long-term BrdU tracking over multiple rounds of replication
      are interpreted. Conversely, the reliable induction of senescence in
      stem/progenitor cells in vitro and in vivo may yield a novel platform for
      molecular studies designed to address multiple aspects of aging and neurogenesis.

PMID- 18802037
TI  - Isolation of primordial germ cells from differentiating human embryonic stem
      cells.
AB  - Of all the cell types that can be obtained from the differentiation of embryonic
      stem cells, primordial germ cells are arguably the most fascinating, as they
      represent the in vitro completion of the reproductive cycle of the organism from
      which the embryonic stem cell line was derived. It is also possible to obtain
      these cells from embryos at an appropriate stage of development, but this process
      yields only small numbers that are not applicable to investigations of their
      epigenetic architecture. A considerable body of data has been generated from the
      differentiation of mouse embryonic stem cells to this cell type, but despite the
      demonstration of their presence in human embryoid bodies, there has been little
      progress toward methods of producing human primordial germ cells in useful
      numbers. We present here a robust protocol to differentiate two human embryonic
      stem cell lines (H9 and hES-NCL1) that maximizes the numbers of primordial germ
      cells that may be obtained using a simple fluorescence-activated cell sorting
      strategy for their isolation. These primordial germ cells demonstrate high-level
      expression of the germ cell-specific VASA gene and show removal of parental
      imprints and chromatin modification changes that support their primordial germ
      cell identity.

PMID- 18802038
TI  - Brain cancer stem cells display preferential sensitivity to Akt inhibition.
AB  - Malignant brain tumors are among the most lethal cancers, and conventional
      therapies are largely limited to palliation. Novel therapies targeted against
      specific molecular pathways may offer superior efficacy and less toxicity than
      conventional therapies, but initial clinical trials of molecular targeted agents
      in brain cancer therapy have been frequently disappointing. In brain tumors and
      other cancers, subpopulations of tumor cells have recently been characterized by
      their ability to self-renew and initiate tumors. Although these cancer stem
      cells, or tumor initiating cells, are often only present in small numbers in
      human tumors, mounting evidence suggests that cancer stem cells contribute to
      tumor maintenance and therapeutic resistance. Thus, the development of therapies
      that target cancer stem cell signal transduction and biology may improve brain
      tumor patient survival. We now demonstrate that populations enriched for cancer
      stem cells are preferentially sensitive to an inhibitor of Akt, a prominent cell
      survival and invasion signaling node. Treatment with an Akt inhibitor more
      potently reduced the numbers of viable brain cancer stem cells relative to
      matched nonstem cancer cells associated with a preferential induction of
      apoptosis and a suppression of neurosphere formation. Akt inhibition also reduced
      the motility and invasiveness of all tumor cells but had a greater impact on
      cancer stem cell behaviors. Furthermore, inhibition of Akt activity in cancer
      stem cells increased the survival of immunocompromised mice bearing human glioma
      xenografts in vivo. Together, these results suggest that Akt inhibitors may
      function as effective anticancer stem cell therapies.

PMID- 18802039
TI  - Secreted proteoglycans directly mediate human embryonic stem cell-basic
      fibroblast growth factor 2 interactions critical for proliferation.
AB  - Human embryonic stem (ES) cells can be maintained in an undifferentiated state if
      the culture medium is first conditioned on a layer of mouse embryonic fibroblast
      (MEF) feeder cells. Here we show that human ES cell proliferation is coordinated
      by MEF-secreted heparan sulfate proteoglycans (HSPG) in conditioned medium (CM).
      These HSPG and other heparinoids can stabilize basic fibroblast growth factor
      (FGF2) in unconditioned medium at levels comparable to those observed in CM. They
      also directly mediate binding of FGF2 to the human ES cell surface, and their
      removal from CM impairs proliferation. Finally, we have developed a purification
      scheme for MEF-secreted HSPG in CM. Using column chromatography, immunoblotting,
      and mass spectrometry-based proteomic analysis, we have identified multiple HSPG
      species in CM. The results demonstrate that HSPG are key signaling cofactors in
      CM-based human ES cell culture.

PMID- 18802040
TI  - Prospective isolation of skeletal muscle stem cells with a Pax7 reporter.
AB  - Muscle regeneration occurs through activation of quiescent satellite cells whose
      progeny proliferate, differentiate, and fuse to make new myofibers. We used a
      transgenic Pax7-ZsGreen reporter mouse to prospectively isolate stem cells of
      skeletal muscle by flow cytometry. We show that Pax7-expressing cells (satellite
      cells) in the limb, head, and diaphragm muscles are homogeneous in size and
      granularity and uniformly labeled by certain cell surface markers, including CD34
      and CD29. The frequency of the satellite cells varies between muscle types and
      with age. Clonal analysis demonstrated that all colonies arising from single
      cells within the Pax7-sorted fraction have myogenic potential. In response to
      injury, Pax7(+) cells reduce CD34, CD29, and CXCR4 expression, increase in size,
      and acquire Sca-1. When directly isolated and cultured in vitro, Pax7(+) cells
      display the hallmarks of activation and proliferate, initially as suspension
      aggregates and later distributed between suspension and adherence. During in
      vitro expansion, Pax7 (ZsGreen) and CD34 expression decline, whereas expression
      of PSA-NCAM is acquired. The nonmyogenic, Pax7(neg) cells expand as Sca1(+)
      PDGRalpha(+) PSA-NCAM(neg) cells. Satellite cells expanded exclusively in
      suspension can engraft and produce dystrophin(+) fibers in mdx(-/-) mice. These
      results establish a novel animal model for the study of muscle stem cell
      physiology and a culture system for expansion of engraftable muscle progenitors.

PMID- 18802041
TI  - Phenotypic and functional reversal within the early human hematopoietic
      compartment.
AB  - The fate of phenotypically defined human hematopoietic stem cells (hHSCs) in
      culture and the link between their surface marker expression profile and function
      are still controversial. We studied these aspects of hHSC biology by relating the
      expression of the early lineage markers (ELM) CD33, CD38, and CD71 on the surface
      of human umbilical cord blood (UCB) CD34(+) cells to their long-term nonobese
      diabetic/severe combined immunodeficient (NOD/SCID) mouse repopulation activity
      (LT-SRA). In uncultured UCB samples, LT-SRA was largely confined to the small
      CD34(+)ELM(-) cell fraction. CD34(+) cells expressing ELM markers at their
      surface usually lacked LT-SRA. After culturing UCB CD34(+) cells for 6 days in
      serum-free medium and on a feeder layer of Rat2 cells, the number of CD34(+)ELM(
      ) cells stayed roughly the same or showed a slight increase and the LT-SRA was
      preserved, suggesting a close association between LT-SRA and the CD34(+)ELM(-)
      phenotype. Indeed, transplantation of CD34(+)ELM(-) cells isolated from cultured
      UCB CD34(+) cells resulted in long-term hematopoietic reconstitution of
      conditioned NOD/SCID mice, whereas CD34(+)ELM(+) cells derived from the same
      cultures were devoid of LT-SRA. Remarkably, roughly 1% of the cells recovered
      from cultures initiated with isolated CD34(+)ELM(+) cells had lost ELM surface
      expression. Concurrently, the cultured CD34(+)ELM(+) cells acquired LT-SRA,
      suggesting that hematopoietic stem cells (HSCs) may arise by the
      dedifferentiation of early hematopoietic progenitor cells. The latter finding
      challenges the paradigm of unidirectional hematopoietic differentiation and opens
      new opportunities for HSC expansion prior to transplantation.

PMID- 18802042
TI  - Comment on "Local accumulation of FOXP3+ regulatory T cells: evidence for an
      immune evasion mechanism in patients with large condylomata acuminata".

PMID- 18802043
TI  - Th1 fate determination in CD4+ T cells: notice is served of the importance of IL
      12!

PMID- 18802044
TI  - Pillars article: development of TH1 CD4+ T cells through IL-12 produced by
      Listeria-induced macrophages. 1993. Science 260(5107): 547-549.

PMID- 18802045
TI  - Transcriptional outcome of Wnt-Frizzled signal transduction in inflammation:
      evolving concepts.
AB  - Wnt-Frizzled signaling was first identified as a key event in Drosophila
      development. Over the years, ample evidence has accumulated regarding the
      multiple roles of Wnt-Frizzled signaling in mammalian cell differentiation and
      tissue/organ morphogenesis. It is thus not surprising that variations in the
      regulatory network of the Wnt signaling scheme would lead to alterations in
      cellular organization and cell activation and to the development of pathogenic
      conditions. Several reports have accordingly implied the involvement of Wnt
      Frizzled signaling in the activation of proinflammatory mediators in inflammatory
      disorders. We will discuss how Wnt-Frizzled signaling may initiate/augment
      inflammation, focusing on its transcriptional outcome.

PMID- 18802046
TI  - Cutting edge: CD25+ regulatory T cells prevent expansion and induce apoptosis of
      B cells specific for tissue autoantigens.
AB  - To study the role of CD25(+) regulatory T cells (T(regs)) in peripheral B cell
      tolerance, we generated transgenic rat insulin promoter RIP-OVA/HEL mice
      expressing the model Ags OVA and HEL in pancreatic islet beta cells (where RIP is
      rat insulin promoter and HEL is hen egg lysozyme). Adoptively transferred
      transgenic OVA-specific CD4(+) and CD8(+) T cells proliferated only in the
      autoantigen-draining pancreatic lymph node (PLN), demonstrating pancreas-specific
      Ag expression. Transferred HEL-specific transgenic B cells (IgHEL cells)
      disappeared within 3 wk from transgenic but not from nontransgenic mice immunized
      with autoantigen. Depletion of CD25(+) FoxP3(+) cells completely restored IgHEL
      cell numbers. T(reg) exerted an analogous suppressive effect on endogenous HEL
      specific autoreactive B cells. T(regs) acted by inhibiting the proliferation of
      IgHEL cells in the spleen and PLN and by systemic induction of their apoptosis.
      Furthermore, they reduced BCR and MHC II surface expression on IgHEL cells in the
      PLN. These findings demonstrate that autoreactive B cells specific for a
      nonlymphoid tissue autoantigen are controlled by T(regs).

PMID- 18802047
TI  - Cutting edge: the mechanism of invariant NKT cell responses to viral danger
      signals.
AB  - Invariant NK T (iNKT) cells influence the response to viral infections, although
      the mechanisms are poorly defined. In this study we show that these innate-like
      lymphocytes secrete IFN-gamma upon culture with CpG oligodeoxynucleotide
      stimulated dendritic cells (DCs) from mouse bone marrow. This requires TLR9
      signaling and IL-12 secretion by the activated DCs, but it does not require CD1d
      expression. iNKT cells also produce IFN-gamma in response to mouse CMV infection.
      Their mechanism of mouse CMV detection is quite similar to that of CpG, requiring
      both TLR9 signaling and IL-12 secretion, while the need for CD1d expression is
      relatively minor. Consequently, iNKT cells have the ability to respond to a
      variety of microbes, including viruses, in an Ag-independent manner, suggesting
      they may play a broad role in antipathogen defenses despite their limited TCR
      repertoire.

PMID- 18802048
TI  - Cutting edge: IL-1 controls the IL-23 response induced by gliadin, the etiologic
      agent in celiac disease.
AB  - IL-23 has been implicated in the pathogenesis of several tissue-specific
      autoimmune diseases. Currently, celiac disease (CD) is the only autoimmune
      disease in which both the major genetic (95% HLA-DQ2(+)) and etiologic factors
      (dietary glutens) for susceptibility are known. We demonstrate that wheat gliadin
      induces significantly greater production of IL-23, IL-1beta, and TNF-alpha in
      PBMC from CD patients compared with HLA-DQ2(+) healthy controls, strongly
      advocating a role for IL-23 in the pathogenesis of CD. Moreover, IL-1beta alone
      triggered IL-23 secretion and the IL-1R antagonist inhibited this response in
      PBMC and purified monocytes. This sequence of events was replicated by beta
      glucan, another substance known to induce IL-23 production. Our results suggest
      that gliadin and beta-glucan stimulate IL-23 secretion through induction of the
      IL-1 signaling pathway and reveal for the first time that the IL-1 system
      regulates IL-23 production. These findings may provide therapeutic targets for
      this disease and other inflammatory conditions mediated by IL-23.

PMID- 18802049
TI  - IFN-gamma-induced TNF-alpha expression is regulated by interferon regulatory
      factors 1 and 8 in mouse macrophages.
AB  - We have previously described that IFN-gamma induces cyclooxygenase 2 and
      inducible NO synthase expression by a mechanism that involved endogenously
      produced TNF-alpha. In this study, we report that TNF-alpha production is induced
      by IFN-gamma treatment in the murine macrophage cell line RAW 264.7. TNF-alpha
      mRNA levels are increased in cells treated with IFN-gamma in a time-dependent
      manner and IFN-gamma also increased human TNF-alpha promoter-dependent
      transcription. Two regions in the TNF-alpha promoter seem to be responsible for
      the IFN-gamma response: a distal region between -1311 and -615 bp of the human
      TNF-alpha promoter, and a proximal region located between -95 and -36 bp upstream
      of the transcriptional start. In contrast, IFN-gamma stimulation induces the
      expression of the transcription factors IRF-1 and IRF-8. Overexpression of these
      transcription factors produces an increase in the transcriptional activity of the
      human TNF-alpha promoter. There is a correlation between the regions of the TNF
      alpha promoter responsible of the transcriptional activation elicited by IRF-1
      and IRF-8 and those required for IFN-gamma response. In addition, IRF-1 and IRF-8
      are recruited to the TNF-alpha promoter in IFN-gamma-treated RAW 264.7 cells, as
      demonstrated by chromatin immunoprecipitation assays. Moreover, overexpression of
      IRF-1 and IRF-8 induces TNF-alpha production in unstimulated RAW 264.7
      macrophages, comparable to the production of TNF-alpha elicited by IFN-gamma
      stimulation, and silencing of IRF-1 and/or IRF-8 with specific small interfering
      RNAs, decreases IFN-gamma-elicited TNF-alpha production. In summary, IFN-gamma
      treatment induces TNF-alpha expression at transcriptional level requiring the
      coordinate action of IRF-1 and IRF-8.

PMID- 18802051
TI  - Hepatitis C virus-specific Th17 cells are suppressed by virus-induced TGF-beta.
AB  - IL-17-secreting T (Th17) cells play a protective role in certain bacterial
      infections, but they are major mediators of inflammation and are pathogenic in
      organ-specific autoimmune diseases. However, human Th17 cells appear to be
      resistant to suppression by CD4(+)CD25(+)FoxP3(+) regulatory T cells, suggesting
      that they may be regulated by alternative mechanisms. Herein we show that IL-10
      and TGF-beta suppressed IL-17 production by anti-CD3-stimulated PBMC from normal
      individuals. TGF-beta also suppressed IL-17 production by purified CD4(+) T
      cells, whereas the inhibitory effect of IL-10 on IL-17 production appears to be
      mediated predominantly by its effect on APC. An examination of patients infected
      with hepatitis C virus (HCV) demonstrated that Ag-specific Th17 cells are induced
      during infection and that these cells are regulated by IL-10 and TGF-beta. PBMC
      from HCV Ab-positive donors secreted IL-17, IFN-gamma, IL-10, and TGF-beta in
      response to stimulation with the HCV nonstructural protein 4 (NS4). Furthermore,
      NS4 induced innate TGF-beta and IL-10 expression by monocytes from normal donors
      and at higher levels from HCV-infected patients. Neutralization of TGF-beta, and
      to a lesser extent IL-10, significantly enhanced NS4-specific IL-17 and IFN-gamma
      production by T cells from HCV-infected donors. Our findings suggest that both
      HCV-specific Th1 and Th17 cells are suppressed by NS4-induced production of the
      innate anti-inflammatory cytokines IL-10 and TGF-beta. This may represent a novel
      immune subversion mechanism by the virus to evade host-protective immune
      responses. Our findings also suggest that TGF-beta and IL-10 play important roles
      in constraining the function of Th17 cells in general.

PMID- 18802050
TI  - Only a subset of phosphoantigen-responsive gamma9delta2 T cells mediate
      protective tuberculosis immunity.
AB  - Mycobacterium tuberculosis and Mycobacterium bovis bacillus Calmette-Guerin (BCG)
      induce potent expansions of human memory Vgamma(9)(+)Vdelta(2)(+) T cells capable
      of IFN-gamma production, cytolytic activity, and mycobacterial growth inhibition.
      Certain phosphoantigens expressed by mycobacteria can stimulate gamma(9)delta(2)
      T cell expansions, suggesting that purified or synthetic forms of these
      phosphoantigens may be useful alone or as components of new vaccines or
      immunotherapeutics. However, we show that while mycobacteria-activated
      gamma(9)delta(2) T cells potently inhibit intracellular mycobacterial growth,
      phosphoantigen-activated gamma(9)delta(2) T cells fail to inhibit mycobacteria,
      although both develop similar effector cytokine and cytolytic functional
      capacities. gamma(9)delta(2) T cells receiving TLR-mediated costimulation during
      phosphoantigen activation also failed to inhibit mycobacterial growth. We
      hypothesized that mycobacteria express Ags, other than the previously identified
      phosphoantigens, that induce protective subsets of gamma(9)delta(2) T cells.
      Testing this hypothesis, we compared the TCR sequence diversity of
      gamma(9)delta(2) T cells expanded with BCG-infected vs phosphoantigen-treated
      dendritic cells. BCG-stimulated gamma(9)delta(2) T cells displayed a more
      restricted TCR diversity than phosphoantigen-activated gamma(9)delta(2) T cells.
      In addition, only a subset of phosphoantigen-activated gamma(9)delta(2) T cells
      functionally responded to mycobacteria-infected dendritic cells. Furthermore,
      differential inhibitory functions of BCG- and phosphoantigen-activated
      gamma(9)delta(2) T cells were confirmed at the clonal level and were not due to
      differences in TCR avidity. Our results demonstrate that BCG infection can
      activate and expand protective subsets of phosphoantigen-responsive
      gamma(9)delta(2) T cells, and provide the first indication that gamma(9)delta(2)
      T cells can develop pathogen specificity similar to alphabeta T cells. Specific
      targeting of protective gamma(9)delta(2) T cell subsets will be important for
      future tuberculosis vaccines.

PMID- 18802052
TI  - Lentiviral-mediated transcriptional targeting of dendritic cells for induction of
      T cell tolerance in vivo.
AB  - Dendritic cells (DCs) are important APCs able to induce both tolerance and
      immunity. Therefore, DCs are attractive targets for immune intervention. However,
      the ex vivo generation and manipulation of DCs at sufficient numbers and without
      changing their original phenotypic and functional characteristics are major
      obstacles. To manipulate DCs in vivo, we developed a novel DC-specific self
      inactivating lentiviral vector system using the 5' untranslated region from the
      DC-STAMP gene as a putative promoter region. We show that a gene therapy approach
      with these DC-STAMP-lentiviral vectors yields long-term and cell-selective
      transgene expression in vivo. Furthermore, transcriptionally targeted DCs induced
      functional, Ag-specific CD4 and CD8 T cell tolerance in vivo, which could not be
      broken by viral immunization. Tolerized CTL were unable to induce autoimmune
      diabetes in a murine autoimmune model system. Therefore, delivering transgenes
      specifically to DCs by using viral vectors might be a promising tool in gene
      therapy.

PMID- 18802054
TI  - Regulatory T cells prevent transfer of type 1 diabetes in NOD mice only when
      their antigen is present in vivo.
AB  - Regulatory T cells (Tregs) can potentially be used as tools to suppress
      pathogenic T cells in autoimmune diseases such as type 1 diabetes. For use in
      therapy it is critically important to determine whether suppression by Tregs
      requires a population specific for the target of autoimmunity, such as pancreatic
      beta cells in type 1 diabetes. Current reports in the NOD mouse model of type 1
      diabetes are in conflict as to whether suppression of disease by Tregs is Ag
      dependent. We have addressed this question by evaluating the effects of islet
      specific TGF-beta-induced Tregs in recipient mice in which the Treg Ag is either
      present or absent. Our data show that Treg numbers in pancreas are reduced in the
      absence of Ag and that there are Ag-dependent differences in the effects of Tregs
      on pathogenic T cells in the pancreas. By examining protection from diabetes
      induced by T cell transfer, we have clearly demonstrated that Tregs suppress only
      in the presence of their Ag and not in mice in which the islets lack the Treg Ag.
      Our results also suggest that in sufficiently large populations of polyclonal
      Tregs, there will be adequate numbers of islet-specific Tregs to suppress
      diabetes.

PMID- 18802053
TI  - Umbilical cord blood T cells express multiple natural cytotoxicity receptors
      after IL-15 stimulation, but only NKp30 is functional.
AB  - The natural cytotoxicity receptors (NCRs) NKp30, NKp44, and NKp46 are thought to
      be NK lineage restricted. Herein we show that IL-15 induces NCR expression on
      umbilical cord blood (UCB) T cells. NCRs were mainly on CD8(+) and CD56(+) UCB T
      cells. Only NKp30 was functional as demonstrated by degranulation, IFN-gamma
      release, redirected killing, and apoptosis. Since NCRs require adaptor proteins
      for function, the expressions of these adaptors were determined. The adaptors
      used by NKp30 and NKp46, FcepsilonR1gamma and CD3zeta, were detected in UCB T
      cells. There was a near absence of DAP12, the adaptor for NKp44, consistent with
      a hypofunctional state. NKp46 was on significantly fewer UCB T cells, possibly
      accounting for its lack of function. Adult peripheral blood (PB) T cells showed
      minimal NCR acquisition after culture with IL-15. Since UCB contains a high
      frequency of naive T cells, purified naive T cells from adult PB were tested.
      Although NKp30 was expressed on a small fraction of naive PB T cells, it was
      nonfunctional. In contrast to UCB, PB T cells lacked FcepsilonR1gamma expression.
      These results demonstrate differences between UCB and PB T cells regarding NCR
      expression and function. Such findings challenge the concept that NCRs are NK
      cell specific.

PMID- 18802055
TI  - Promoter analysis reveals critical roles for SMAD-3 and ATF-2 in expression of IL
      23 p19 in macrophages.
AB  - IL-23 p19/p40, produced by macrophages and dendritic cells, is critical for
      development of Th17 in several autoimmune diseases. In this study, bone marrow
      derived (BMM) and splenic macrophages (SPM) from SJL/J mice, susceptible to
      autoimmune demyelinating disease following Theiler's virus (TMEV) infection,
      expressed IL-23 in response to TMEV. We identified potential binding sites for
      IFN response factor (IRF)-3 (nt -734 to -731), Sma- and Mad-related protein
      (SMAD)-3 (nt -584 to -581), activating transcription factor (ATF)-2 (nt -571 to 
      568), IRF-7 (nt -533 to-525), and NF-kappaB (nt -215 to -209) in the murine p19
      promoter. The p19(prom) in the pGL3 promoter-reporter vector responded to TMEV or
      poly(I:C), a TLR3 agonist in the RAW264.7 macrophage cell line. Deletions
      upstream from the IRF-3 site and mutations at the IRF-3, SMAD-3, ATF-2, or NF
      kappaB, but not the IRF-7, sites significantly reduced promoter activity. ATF-2
      or SMAD-3, but not IRF-3, short-hairpin RNA reduced p19 promoter activity and
      protein expression in RAW264.7 cells responding to TMEV. Chromosomal DNA
      immunoprecipitation assays revealed that SMAD-3 and ATF-2 bind to the endogenous
      p19 promoter in RAW264.7 cells and SJL/J SPM following challenge with TMEV. TGF
      beta1, which activates SMAD-3, was induced in RAW264.7 cells, BMM, and SPM by
      TMEV. Neutralizing Ab to TGF-beta1 eliminated TMEV-induced IL-23 production and
      SMAD-3 activation in RAW264.7 cells, BMM, and SPM. Activation of ATF-2 was JNK,
      but not p38 or ERK MAPK dependent. Inhibition of the JNK, but also the ERK MAPK
      pathways decreased expression of p19. These results suggest that ATF-2 and SMAD-3
      are transcription factors, which are, in addition to NF-kappaB, essential for IL
      23 p19 expression.

PMID- 18802056
TI  - Bone marrow-derived dendritic cells generated in the presence of resolvin E1
      induce apoptosis of activated CD4+ T cells.
AB  - In contrast to the role of dendritic cells (DC) in immunity and tolerance, little
      is known about their possible role in the resolution of inflammatory processes.
      In addition to the reduction in the number of infiltrating immune cells, the
      elimination of effector T cells already present at the inflammatory site
      represents an essential step toward resolution. Recently, lipid mediators such as
      the omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid and their
      metabolites, including resolvin E1 (RvE1), have been shown to accumulate in
      inflammatory foci during the resolution phase. RvE1 has been reported to reduce
      immune cell infiltration and proinflammatory cytokine production. In this study
      we report that DC exposed to RvE1, especially during differentiation, acquire the
      capacity to induce apoptosis of activated T cells through the induction and
      activity of indoleamine 2,3-dioxygenase. To our knowledge, this study is the
      first to report on an omega-3 fatty acid derivative inducing indoleamine 2,3
      dioxygenase expression in DC. RvE1-exposed DC maintain an immature chemokine
      receptor expression pattern even following TLR stimulation, with high CCR5 and no
      CCR7 expression. This effect implies that DC exposed to RvE1 and pathogens remain
      at the inflammatory site, instead of migrating to lymph nodes, and induce
      apoptosis in effector T cells infiltrating the inflammatory site. To our
      knowledge, the DC described in this study represent a new functional DC subtype,
      whose essential function resides in the resolution of inflammation.

PMID- 18802057
TI  - Disruption of the transcription factor Nrf2 promotes pro-oxidative dendritic
      cells that stimulate Th2-like immunoresponsiveness upon activation by ambient
      particulate matter.
AB  - Oxidative stress is important in dendritic cell (DC) activation. Environmental
      particulate matter (PM) directs pro-oxidant activities that may alter DC
      function. Nuclear erythroid 2 p45-related factor 2 (Nrf2) is a redox-sensitive
      transcription factor that regulates expression of antioxidant and detoxification
      genes. Oxidative stress and defective antioxidant responses may contribute to the
      exacerbations of asthma. We hypothesized that PM would impart differential
      responses by Nrf2 wild-type DCs as compared with Nrf2(-/-) DCs. We found that the
      deletion of Nrf2 affected important constitutive functions of both bone marrow
      derived and highly purified myeloid lung DCs such as the secretion of
      inflammatory cytokines and their ability to take up exogenous Ag. Stimulation of
      Nrf2(-/-) DCs with PM augmented oxidative stress and cytokine production as
      compared with resting or Nrf2(+/+) DCs. This was associated with the enhanced
      induction of Nrf2-regulated antioxidant genes. In contrast to Nrf2(+/+) DCs,
      coincubation of Nrf2(-/-) DCs with PM and the antioxidant N-acetyl cysteine
      attenuated PM-induced up-regulation of CD80 and CD86. Our studies indicate a
      previously underappreciated role of Nrf2 in innate immunity and suggest that
      deficiency in Nrf2-dependent pathways may be involved in susceptibility to the
      adverse health effects of air pollution in part by promoting Th2 cytokine
      responses in the absence of functional Nrf2. Moreover, our studies have uncovered
      a hierarchal response to oxidative stress in terms of costimulatory molecule
      expression and cytokine secretion in DCs and suggest an important role of
      heightened oxidative stress in proallergic Th2-mediated immune responses
      orchestrated by DCs.

PMID- 18802058
TI  - Activation of nonclassical CD1d-restricted NK T cells induces airway
      hyperreactivity in beta 2-microglobulin-deficient mice.
AB  - Allergic asthma is characterized by Th2-driven eosinophilic airway inflammation
      and by a central feature called airway hyperreactivity (AHR), development of
      which requires the presence of classical type I invariant NK T (iNKT) cells.
      Allergen-induced AHR, however, develops in beta(2)-microglobulin (beta(2)m)(-/-)
      mice, which lack classical iNKT cells, suggesting that in some situations iNKT
      cells may be dispensable for the development of AHR. In contrast, our studies now
      suggest that a CD1d-restricted, NK1.1(+) noninvariant TCR NKT cell population is
      present in beta(2)m(-/-) mice and is responsible for the development of AHR but
      not for Th2 responses. Furthermore, treatment of beta(2)m(-/-) mice with anti
      CD1d mAb or anti-NK1.1 mAb unexpectedly abolished allergen-induced AHR. The CD1
      restricted NKT cells in these mice, which failed to respond to alpha
      galactosylceramide and which therefore were not classical type I iNKT cells,
      appear to represent an NKT cell subset restricted by a beta(2)m-independent form
      of CD1d. These results indicate that, although classical type I iNKT cells are
      normally required for the development of AHR, under different circumstances other
      NKT cell subsets, including nonclassical NKT cells, may substitute for classical
      iNKT cells and induce AHR.

PMID- 18802059
TI  - Galectin-1 promotes immunoglobulin production during plasma cell differentiation.
AB  - Galectin-1, a beta-galactoside-binding soluble lectin, has been implicated in
      regulating immune system homeostasis. We investigated the function of galectin-1
      in plasma cell differentiation and found that it is induced in primary murine and
      human differentiating B cells. B lymphocyte-induced maturation protein-1 (Blimp
      1), a master regulator for plasma cell differentiation, was necessary and
      sufficient to induce galectin-1 expression. Notably, ectopic expression of
      galectin-1 in mature B cells increased Ig mu-chain transcript levels as well as
      the overall level of Ig production. This function of galectin-1 was dependent on
      binding to cell surface glycosylated counter receptors, as a galectin-1 mutant
      deficient in beta-galactoside binding showed diminished ability to promote Ig
      production. Extracellular galectin-1 bound more significantly to mature B cells
      than to plasma cells. Lastly, we found that the sugar compound N
      acetyllactosamine blocked the binding of galectin-1 to murine splenic B cells and
      inhibited their differentiation. Taken together, these data are the first to
      demonstrate a role for galectin-1 in promoting Ig production during plasma cell
      differentiation.

PMID- 18802060
TI  - Donor deficiency of decay-accelerating factor accelerates murine T cell-mediated
      cardiac allograft rejection.
AB  - Decay-accelerating factor (DAF) is a cell surface regulator that accelerates the
      dissociation of C3/C5 convertases and thereby prevents the amplification of
      complement activation on self cells. In the context of transplantation, DAF has
      been thought to primarily regulate antibody-mediated allograft injury, which is
      in part serum complement-dependent. Based on our previously delineated link
      between DAF and CD4 T cell responses, we evaluated the effects of donor Daf1 (the
      murine homolog of human DAF) deficiency on CD8 T cell-mediated cardiac allograft
      rejection. MHC-disparate Daf1(-/-) allografts were rejected with accelerated
      kinetics compared with wild-type grafts. The accelerated rejection predominantly
      tracked with DAF's absence on bone marrow-derived cells in the graft and required
      allograft production of C3. Transplantation of Daf1(-/-) hearts into wild-type
      allogeneic hosts augmented the strength of the anti-donor (direct pathway) T cell
      response, in part through complement-dependent proliferative and pro-survival
      effects on alloreactive CD8 T cells. The accelerated allograft rejection of Daf1(
      /-) hearts occurred in recipients lacking anti-donor Abs. The results reveal that
      donor DAF expression, by controlling local complement activation on interacting T
      cell APC partners, regulates the strength of the direct alloreactive CD8(+) T
      cell response. The findings provide new insights into links between innate and
      adaptive immunity that could be exploited to limit T cell-mediated injury to an
      allograft following transplantation.

PMID- 18802062
TI  - Differential susceptibility of allogeneic targets to indirect CD4 immunity
      generates split tolerance.
AB  - CD4 T cells frequently help to activate CD8 T and B cells that effect transplant
      rejection. However, CD4 T cells alone can reject transplants, either directly or
      indirectly. The relative effectiveness of indirect CD4 immunity in rejecting
      different types of allogeneic grafts is unknown. To address this, we used a TCR
      transgenic mouse model in which indirect CD4 alloimmunity alone can be studied.
      We challenged transgenic recipients with hematopoietic cells and shortly
      thereafter skin transplants that could only be rejected indirectly, and observed
      Ag-specific indirect donor B cell and skin rejection, but not T cell elimination,
      reflecting a state of split tolerance. Deficiency of indirect CD4 alloimmunity in
      donor T cell rejection was also apparent when acute indirect rejection of donor
      islets occurred despite generation and maintenance of mixed T cell chimerism, due
      to migration of the few passenger T cells into recipient circulation. Although
      passenger lymphocytes delayed indirect islet rejection, they enhanced rejection
      by a full repertoire capable of both direct and indirect reactivity.
      Interestingly, the persistence of chimerism was associated with the eventual
      development of tolerance, as demonstrated by acceptance of donor skin grafts
      given late to hematopoietic cell recipients, and hyporesponsiveness of transgenic
      T cells from islet recipients in vitro. Mechanistically, tolerance was recessive
      and associated with progressive down-regulation of CD4. Collectively, our data
      indicate that indirect CD4 immunity is not equally destructive toward different
      types of allogeneic grafts, the deficiency of which generates split tolerance.
      The futility of these responses can convert immunity into tolerance.

PMID- 18802061
TI  - Early growth response genes regulate B cell development, proliferation, and
      immune response.
AB  - Egr-1 (early growth response gene-1) is an immediate early gene encoding a zinc
      finger motif-containing transcription factor. Upon cross-linking of BCR, mature B
      cells undergo proliferation with an increase in Egr-1 message. Immature B
      lymphoma cells that express Egr-1 message and protein constitutively are growth
      inhibited when Egr-1 is down-regulated by negative signals from BCR or by
      antisense oligonucleotides. To test the hypothesis that Egr-1 is important for B
      cell development, we examined B cells from primary and secondary lymphoid organs
      in Egr-1(-/-) mice. Marginal zone B cell development was arrested in these mice,
      whereas the B cells in all other compartments were increased. To test the
      hypothesis that Egr-1 function may be partially compensated by other Egr family
      members, we developed transgenic mice expressing a dominant negative form of Egr
      1, which lacks the trans activation domain but retains the DNA-binding domain, in
      a B cell-specific manner. There was a decrease in B lymphopoiesis in the bone
      marrow accompanied by a reduction in splenic immature and mature B cells as well
      as marginal zone B cells in the transgenic mice. Moreover, transgenic mice
      respond poorly to BCR cross-linking in vitro and T-independent and T-dependent
      Ags in vivo.

PMID- 18802063
TI  - T cells from Leishmania major-susceptible BALB/c mice have a defect in
      efficiently up-regulating CXCR3 upon activation.
AB  - Genetic background influences the outcome of Leishmania major infection. C57BL/6
      mice mount a Th1 response and resolve infection. In contrast, BALB/c mice mount a
      Th2 response and develop chronic lesions. This susceptible phenotype is seen even
      though BALB/c mice generate IFN-gamma-producing T cells at proportions similar to
      C57BL/6 mice in their lymph nodes (LN) early after infection. We had previously
      shown that chemokine receptor CXCR3 mediates immunity against L. major by
      recruiting IFN-gamma-producing T cells to the lesions of C57BL/6 mice. Therefore,
      we hypothesized that IFN-gamma-secreting T cells in BALB/c mice are unable to
      confer protection because they may be defective in up-regulating CXCR3. To test
      this hypothesis, we analyzed kinetics of CXCR3-expressing T cells in the LN and
      lesions of BALB/c and C57BL/6 mice during L. major infection. Additionally, we
      compared the ability of T cells from BALB/c and C57BL/6 mice to up-regulate CXCR3
      upon activation. We found that resolution of L. major infection in C57BL/6 mice
      was associated with an increase in the proportion of CXCR3(+) T cells in regional
      LN and lesions, whereas disease progression in BALB/c mice was associated with a
      decrease in these populations. Anti-CD3/CD28-activated T cells from naive BALB/c
      but not C57BL/6 mice were defective in up-regulating CXCR3. Impaired induction of
      CXCR3 on BALB/c T cells was not due to lack of IFN-gamma and was mediated
      partially by IL-10 but not IL-4 or IL-13. We propose that defective CXCR3 up
      regulation on T cells in BALB/c mice may contribute to L. major susceptibility.

PMID- 18802064
TI  - Induction of a VLA-2 (CD49b)-expressing effector T cell population by a cell
      based neuroblastoma vaccine expressing CD137L.
AB  - In malignancies where no universally expressed dominant Ag exists, the use of
      tumor cell-based vaccines has been proposed. We have modified a mouse
      neuroblastoma cell line to express either CD80 (B7.1), CD137L (4-1BBL), or both
      receptors on the tumor cell surface. Vaccines expressing both induce a strong T
      cell response that is unique in that among responding CD8 T cells, a T effector
      memory cell (T(EM)) response arises in which a large number of the T(EM) express
      the alpha-chain of VLA-2, CD49b. We demonstrate using both in vitro and in vivo
      assays that the CD49b(+) CD8 T cell population is a far more potent antitumor
      effector cell population than nonfractionated CD8 or CD49b(-) CD8 T cells and
      that CD49b on vaccine-induced CD8 T cells mediates invasion of a collagen matrix.
      In in vivo rechallenge studies, CD49b(+) T cells no longer expanded, indicating
      that CD49b T(EM) expansion is restricted to the initial response to vaccine. To
      demonstrate a mechanistic link between the expression of costimulatory molecules
      on the vaccine and CD49b on responding T cells, we stimulated naive T cells in
      vitro with artificial APC expressing different combinations of anti-CD3, anti
      CD28, and CD137L. Although some mRNA encoding CD49b was induced by combining anti
      CD3 with anti-CD28 or CD137L, the highest level was induced when all three
      signals were present. This indicates that CD49b expression results from additive
      costimulation and that the level of CD49b message serves as an indicator of the
      effectiveness of T cell activation by a cell-based vaccine.

PMID- 18802065
TI  - Monocyte migration and LFA-1-mediated attachment to brain microvascular
      endothelia is regulated by SDF-1 alpha through Lyn kinase.
AB  - Infiltration of activated monocytes into the brain is a prerequisite for the
      development of various neurological disorders such as HIV-associated dementia,
      multiple sclerosis, and other inflammatory processes. In these pathologies, the
      chemokine SDF-1alpha (CXCL12) is over-expressed and might attract monocytes into
      the CNS. We demonstrate here that SDF-1alpha stimulates migration of monocytes
      through its receptor, CXCR4, and decreases monocyte adherence to surfaces coated
      with ICAM-1, a ligand for beta(2) integrins. SDF-1alpha also decreases monocyte
      adherence to brain microvascular endothelial cells (BMVEC) that are activated
      with TNF-alpha, IL-1beta, or recombinant envelope glycoprotein from HIV-1, which
      increase BMVEC expression of ICAM-1. The decreased adherence is linked to down
      regulation on monocytes of the activation-dependent epitope of the beta(2)
      integrin LFA-1 by SDF-1alpha. Knockdown of Lyn in monocytes using small
      interfering RNA decreases SDF-1alpha-mediated migration and prevents the
      inhibition of monocyte attachment to ICAM-1 and activated BMVEC. Thus, in SDF
      1alpha-stimulated monocytes, Lyn acts as a positive regulator of migration and a
      negative regulator of adhesion to BMVEC through the LFA-1 integrin. These results
      provide a novel Lyn-mediated signaling mechanism for the regulation of monocyte
      movement at the blood-brain barrier.

PMID- 18802066
TI  - Intrinsic and induced regulation of the age-associated onset of spontaneous
      experimental autoimmune encephalomyelitis.
AB  - Multiple sclerosis is characterized by perivascular CNS infiltration of myelin
      specific CD4(+) T cells and activated mononuclear cells. TCR transgenic mice on
      the SJL background specific for proteolipid protein (PLP)(139-151) develop a high
      incidence of spontaneous experimental autoimmune encephalomyelitis (sEAE). We
      examined the intrinsic mechanisms regulating onset and severity of sEAE. CD4(+) T
      cells isolated from the cervical lymph nodes, but not spleens, of diseased 5B6
      transgenic mice are hyperactivated when compared with age-matched healthy mice
      and produce both IFN-gamma and IL-17, indicating that the cervical lymph node is
      the initial peripheral activation site. The age-associated development of sEAE
      correlates with a decline in both the functional capacity of natural regulatory T
      cells (nTregs) and in PLP(139-151)-induced IL-10 production and a concomitant
      increase in IL-17 production. Anti-CD25-induced inactivation of nTregs increased
      the incidence and severity of sEAE. Conversely, induction of peripheral tolerance
      via the i.v. injection of PLP(139-151)-pulsed, ethylcarbodiimide-fixed APCs
      (PLP(139-151)-SP) inhibited the development of clinical disease concomitant with
      increased production of IL-10 and conversion of Foxp3(+) Tregs from CD4(+)CD25(-)
      progenitors. These data indicate that heterogeneous populations of Tregs regulate
      onset of sEAE, and that induction of peripheral tolerance can be exploited to
      prevent/treat spontaneous autoimmune disease.

PMID- 18802067
TI  - Swift entry of myelin-specific T lymphocytes into the central nervous system in
      spontaneous autoimmune encephalomyelitis.
AB  - Strong evidence supports that CNS-specific CD4(+) T cells are central to the
      pathogenesis of multiple sclerosis and experimental autoimmune encephalomyelitis
      (EAE). Using a model of spontaneous EAE, we demonstrated that myelin basic
      protein (MBP)-specific CD4(+) T cells up-regulate activation markers in the CNS
      draining cervical lymph nodes at a time when there is no T cell activation
      anywhere else, including the CNS, and before the appearance of clinical signs. In
      spontaneous EAE, the number of MBP-specific T cell numbers does not build up
      gradually in the CNS; instead, a swift migration of IFN-gamma-producing T cells
      into the CNS takes place approximately 24 h before the onset of neurological
      signs of EAE. Surgical excision of the cervical lymph nodes in healthy pre-EAE
      transgenic mice delayed the onset of EAE and resulted in a less severe disease.
      In EAE induced by immunization with MBP/CFA, a similar activation of T cells in
      the draining lymph nodes of the injection site precedes the disease. Taken
      together, our results suggest that peripheral activation of T cells in draining
      lymph nodes is an early event in the development of EAE, which paves the way for
      the initial burst of IFN-gamma-producing CD4(+) T cell into the CNS.

PMID- 18802068
TI  - Novel role of IL-13 in fibrosis induced by nonalcoholic steatohepatitis and its
      amelioration by IL-13R-directed cytotoxin in a rat model.
AB  - Nonalcoholic steatohepatitis (NASH), the most common cause of chronic liver
      fibrosis, progresses to cirrhosis in up to 20% of patients. We report that
      hepatic stellate cells (HSC) in sinusoidal lesions of liver of patients with NASH
      express high levels of high-affinity IL-13R (IL-13Ralpha2), which is colocalized
      with smooth muscle actin, whereas fatty liver and normal liver specimens do not
      express IL-13Ralpha2. HSCs engineered to overexpress IL-13Ralpha2 respond to IL
      13 and induce TGFB1 promoter activity and TGF-beta1 production. We also developed
      NASH in rats by feeding a choline-deficient l-amino acid diet. These rats
      developed liver fibrosis as assessed by H&E staining, Masson's trichrome and
      Sirius red staining, and hydroxyproline assays. Treatment of these rats with IL
      13R-directed cytotoxin caused a substantial decline in fibrosis and liver enzymes
      without organ toxicity. These studies demonstrate that functional IL-13Ralpha2
      are overexpressed in activated HSCs involved in NASH and that IL-13 cytotoxin
      ameliorates pathological features of NASH in rat liver, indicating a novel role
      of this cytotoxin in potential therapy.

PMID- 18802069
TI  - Proinflammatory S100 proteins regulate the accumulation of myeloid-derived
      suppressor cells.
AB  - Chronic inflammation is a complex process that promotes carcinogenesis and tumor
      progression; however, the mechanisms by which specific inflammatory mediators
      contribute to tumor growth remain unclear. We and others recently demonstrated
      that the inflammatory mediators IL-1beta, IL-6, and PGE(2) induce accumulation of
      myeloid-derived suppressor cells (MDSC) in tumor-bearing individuals. MDSC impair
      tumor immunity and thereby facilitate carcinogenesis and tumor progression by
      inhibiting T and NK cell activation, and by polarizing immunity toward a tumor
      promoting type 2 phenotype. We now show that this population of immature myeloid
      cells induced by a given tumor share a common phenotype regardless of their in
      vivo location (bone marrow, spleen, blood, or tumor site), and that
      Gr1(high)CD11b(high)F4/80(-)CD80(+)IL4Ralpha(+/-)Arginase(+) MDSC are induced by
      the proinflammatory proteins S100A8/A9. S100A8/A9 proteins bind to carboxylated N
      glycans expressed on the receptor for advanced glycation end-products and other
      cell surface glycoprotein receptors on MDSC, signal through the NF-kappaB
      pathway, and promote MDSC migration. MDSC also synthesize and secrete S100A8/A9
      proteins that accumulate in the serum of tumor-bearing mice, and in vivo blocking
      of S100A8/A9 binding to MDSC using an anti-carboxylated glycan Ab reduces MDSC
      levels in blood and secondary lymphoid organs in mice with metastatic disease.
      Therefore, the S100 family of inflammatory mediators serves as an autocrine
      feedback loop that sustains accumulation of MDSC. Since S100A8/A9 activation of
      MDSC is through the NF-kappaB signaling pathway, drugs that target this pathway
      may reduce MDSC levels and be useful therapeutic agents in conjunction with
      active immunotherapy in cancer patients.

PMID- 18802070
TI  - A novel role for CD4+ T cells in the control of cachexia.
AB  - Cachexia is the dramatic weight loss and muscle atrophy seen in chronic disease
      states, including autoimmunity, cancer, and infection, and is often associated
      with lymphopenia. We have previously shown that CD4(+) T cells that express the
      lowest density of CD44 (CD4(+)CD44(v.low)) are significantly reduced in diabetic
      NOD mice that are cachexic compared with diabetic mice that are not cachexic.
      Using this model, and a model of cancer cachexia, we test the hypothesis that
      CD4(+)CD44(v.low) cells play an active role in protecting the host from cachexia.
      CD4(+)CD44(v.low) cells, but not CD4(+) cells depleted of CD44(v.low) cells,
      delay the onset of wasting when infused into either diabetic or prediabetic NOD
      recipients. However, no significant effect on the severity of diabetes was
      detected. In a model of cancer cachexia, they significantly reduce muscle
      atrophy, and inhibit muscle protein loss and DNA loss, even when given after the
      onset of cachexia. Protection from wasting and muscle atrophy by
      CD4(+)CD44(v.low) cells is associated with protection from lymphopenia. These
      data suggest, for the first time, a role for an immune cell subset in protection
      from cachexia, and further suggest that the mechanism of protection is
      independent of protection from autoimmunity.

PMID- 18802071
TI  - Nicotinamide phosphoribosyl transferase/pre-B cell colony-enhancing
      factor/visfatin is required for lymphocyte development and cellular resistance to
      genotoxic stress.
AB  - Nicotinamide phosphoribosyl transferase (Nampt)/pre-B cell colony-enhancing
      factor (PBEF)/visfatin is a protein displaying multiple functional properties.
      Originally described as a cytokine-like protein able to regulate B cell
      development, apoptosis, and glucose metabolism, this protein also plays an
      important role in NAD biosynthesis. To gain insight into its physiological role,
      we have generated a mouse strain expressing a conditional Nampt allele. Lack of
      Nampt expression strongly affects development of both T and B lymphocytes.
      Analysis of hemizygous cells and in vitro cell lines expressing distinct levels
      of Nampt illustrates the critical role of this protein in regulating
      intracellular NAD levels. Consequently, a clear relationship was found between
      intracellular Nampt levels and cell death in response to the genotoxic agent MNNG
      (N-methyl-N'-nitro-N-nitrosoguanidine), confirming that this enzyme represents a
      key regulator of cell sensitivity to NAD-consuming stress secondary to poly(ADP
      ribose) polymerases overactivation. By using mutant forms of this protein and a
      well-characterized pharmacological inhibitor (FK866), we unequivocally
      demonstrate that the ability of the Nampt to regulate cell viability during
      genotoxic stress requires its enzymatic activity. Collectively, these data
      demonstrate that Nampt participates in cellular resistance to genotoxic/oxidative
      stress, and it may confer to cells of the immune system the ability to survive
      during stressful situations such as inflammation.

PMID- 18802072
TI  - Protein kinase C-theta is required for efficient positive selection.
AB  - Protein kinase C-theta (PKCtheta) is critical for TCR-initiated signaling in
      mature T cells, but initial reports found no requirement for PKCtheta in
      thymocyte development. Thymocytes and peripheral T cells utilize many of the same
      signaling components and, given the significant role of PKCtheta in peripheral T
      cells, it was surprising that it was not involved at all in TCR signaling in
      thymocytes. We decided to re-evaluate the role of PKCtheta in thymocyte
      development using the well-characterized class II-restricted n3.L2 TCR-transgenic
      TCR model. Analysis of n3.L2 PKCtheta(-/-) mice revealed a defect in thymocyte
      positive selection, resulting in a 50% reduction in the generation of n3.L2 CD4
      single-positive thymocytes and n3.L2 CD4 mature T cells. Competition between
      n3.L2 WT and n3.L2 PKCtheta(-/-) thymocytes in bone marrow chimeras revealed a
      more dramatic defect, with a >80% reduction in generation of n3.L2 CD4 single
      positive thymocytes derived from PKCtheta(-/-) mice. Inefficient positive
      selection of n3.L2 PKCtheta(-/-) CD4 single-positive cells resulted from "weaker"
      signaling through the TCR and correlated with diminished ERK activation. The
      defect in positive selection was not complete in the PKCtheta(-/-) mice, most
      likely accounted for by compensation by other PKC isoforms not evident in
      peripheral cells. Similar decreased positive selection of both CD4 and CD8 single
      positive thymocytes was also seen in nontransgenic PKCtheta(-/-) mice. These
      findings now place PKCtheta as a key signaling molecule in the positive selection
      of thymocytes as well as in the activation of mature T cells.

PMID- 18802073
TI  - Goblet cell-derived resistin-like molecule beta augments CD4+ T cell production
      of IFN-gamma and infection-induced intestinal inflammation.
AB  - The secreted goblet cell-derived protein resistin-like molecule beta (RELMbeta)
      has been implicated in divergent functions, including a direct effector function
      against parasitic helminths and a pathogenic function in promoting inflammation
      in models of colitis and ileitis. However, whether RELMbeta influences CD4(+) T
      cell responses in the intestine is unknown. Using a natural model of intestinal
      inflammation induced by chronic infection with gastrointestinal helminth
      Trichuris muris, we identify dual functions for RELMbeta in augmenting CD4(+) Th1
      cell responses and promoting infection-induced intestinal inflammation. Following
      exposure to low-dose Trichuris, wild-type C57BL/6 mice exhibit persistent
      infection associated with robust IFN-gamma production and intestinal
      inflammation. In contrast, infected RELMbeta(-/-) mice exhibited a significantly
      reduced expression of parasite-specific CD4(+) T cell-derived IFN-gamma and TNF
      alpha and failed to develop Trichuris-induced intestinal inflammation. In in
      vitro T cell differentiation assays, recombinant RELMbeta activated macrophages
      to express MHC class II and secrete IL-12/23p40 and enhanced their ability to
      mediate Ag-specific IFN-gamma expression in CD4(+) T cells. Taken together, these
      data suggest that goblet cell-macrophage cross-talk, mediated in part by
      RELMbeta, can promote adaptive CD4(+) T cell responses and chronic inflammation
      following intestinal helminth infection.

PMID- 18802074
TI  - Protein kinase C delta localizes to secretory lysosomes in CD8+ CTL and directly
      mediates TCR signals leading to granule exocytosis-mediated cytotoxicity.
AB  - Lytic granule exocytosis is the major effector function used by CD8(+) CTL in
      response to intracellular pathogens and tumors. Despite recent progress in the
      field, two important aspects of this cytotoxic mechanism remain poorly
      understood. First, TCR-signaling pathway(s) that selectively induces granule
      exocytosis in CTL has not been defined to date. Second, it is unclear how Ag
      receptor-induced signals are converted into mobilization of lytic granules. We
      recently demonstrated that protein kinase C delta (PKC delta) selectively
      regulates TCR-induced lytic granule polarization in mouse CD8(+) CTL. To better
      understand how PKC delta facilitates granule movement, here we studied dynamics
      of intracellular localization of PKC delta in living CD8(+) CTL. Strikingly, we
      found that PKC delta localizes to the secretory lysosomes and polarizes toward
      immunological synapse during the process of target cell killing. Also,
      biochemical and structure-function studies demonstrated that upon TCR ligation,
      PKC delta becomes rapidly phosphorylated on the activation loop and regulates
      granule exocytosis in a kinase-dependent manner. Altogether, our current studies
      provide new insights concerning the regulation of TCR-induced lytic granule
      exocytosis by revealing novel intracellular localization of PKC delta, providing
      the first example of colocalization of a kinase with secretory lysosomes in
      CD8(+) CTL and demonstrating that PKC delta directly transduces TCR signals
      leading to polarized granule secretion.

PMID- 18802075
TI  - Arrestin 3 mediates endocytosis of CCR7 following ligation of CCL19 but not
      CCL21.
AB  - Internalization of ligand bound G protein-coupled receptors, an important
      cellular function that mediates receptor desensitization, takes place via
      distinct pathways, which are often unique for each receptor. The C-C chemokine
      receptor (CCR7) G protein-coupled receptor is expressed on naive T cells,
      dendritic cells, and NK cells and has two endogenous ligands, CCL19 and CCL21.
      Following binding of CCL21, 21 +/- 4% of CCR7 is internalized in the HuT 78 human
      T cell lymphoma line, while 76 +/- 8% of CCR7 is internalized upon binding to
      CCL19. To determine whether arrestins mediated differential internalization of
      CCR7/CCL19 vs CCR7/CCL21, we used small interfering RNA (siRNA) to knock down
      expression of arrestin 2 or arrestin 3 in HuT 78 cells. Independent of arrestin 2
      or arrestin 3 expression, CCR7/CCL21 internalized. In contrast, following
      depletion of arrestin 3, CCR7/CCL19 failed to internalize. To examine the
      consequence of complete loss of both arrestin 2 and arrestin 3 on CCL19/CCR7
      internalization, we examined CCR7 internalization in arrestin 2(-/-)/arrestin 3(
      /-) murine embryonic fibroblasts. Only reconstitution with arrestin 3-GFP but not
      arrestin 2-GFP rescued internalization of CCR7/CCL19. Loss of arrestin 2 or
      arrestin 3 blocked migration to CCL19 but had no effect on migration to CCL21.
      Using immunofluorescence microscopy, we found that arrestins do not cluster at
      the membrane with CCR7 following ligand binding but cap with CCR7 during receptor
      internalization. These are the first studies that define a role for arrestin 3 in
      the internalization of a chemokine receptor following binding of one but not both
      endogenous ligands.

PMID- 18802076
TI  - Induction of IL-17+ T cell trafficking and development by IFN-gamma: mechanism
      and pathological relevance in psoriasis.
AB  - Th1 and Th17 T cells are often colocalized in pathological environments, yet Th1
      derived IFN-gamma inhibits Th17 cell development in vitro. We explored the
      physiologic basis of this paradox in humans. In this study, we demonstrate
      increased the number of CD4(+) and CD8(+) IL-17(+) T cells in skin lesions of
      psoriasis. Furthermore, we show that myeloid APCs potently support induction of
      IL-17(+) T cells, and that this activity is greatly increased in psoriasis. We
      tested stimuli that might account for this activity. Th1 cells and IFN-gamma are
      increased in psoriatic blood and lesional skin. We show that IFN-gamma programs
      myeloid APCs to induce human IL-17(+) T cells via IL-1 and IL-23. IFN-gamma also
      stimulates APC production of CCL20, supporting migration of IL-17(+) T cells, and
      synergizes with IL-17 in the production of human beta-defensin 2, an
      antimicrobial and chemotactic protein highly overexpressed by psoriatic
      keratinocytes. This study reveals a novel mechanistic interaction between Th1 and
      IL-17(+) T cells, challenges the view that Th1 cells suppress Th17 development
      through IFN-gamma, and suggests that Th1 and IL-17(+) T cells may collaboratively
      contribute to human autoimmune diseases.

PMID- 18802077
TI  - Inhibitory immunoglobulin-like receptors LILRB and PIR-B negatively regulate
      osteoclast development.
AB  - Osteoclasts, multinucleated cells of myeloid-monocytic origin, are responsible
      for bone resorption, which is crucial for maintenance of bone homeostasis in
      concert with bone-forming osteoblasts of nonhematopoietic, mesenchymal origin.
      Receptor activator of NF-kappaB ligand (RANKL) and M-CSF, expressed on the
      surface of and secreted by osteoblasts, respectively, are essential factors that
      facilitate osteoclast formation. In contrast to the activation processes for
      osteoclast formation, inhibitory mechanisms for it are poorly understood. Herein
      we demonstrate that inhibitory Ig-like receptors recruiting Src homology 2 domain
      containing tyrosine phosphatase 1 (SHP-1) are expressed on osteoclast precursor
      cells like other myeloid cells, and that they play a regulatory role in the
      development of osteoclasts. We detected cell-surface expression of paired Ig-like
      receptor (PIR)-B and four isoforms of leukocyte Ig-like receptor (LILR)B on
      cultured osteoclast precursor cells of mouse and human origin, respectively, and
      showed that all of these ITIM-harboring inhibitory receptors constitutively
      recruit SHP-1 in the presence of RANKL and M-CSF, and that some of them can
      suppress osteoclast development in vitro. Fluorescence energy transfer analyses
      have suggested that the constitutive binding of either murine PIR-B or its human
      ortholog LILRB1 to MHC class I molecules on the same cell surface comprises one
      of the mechanisms for developmental regulation. These results constitute the
      first evidence of the regulation of osteoclast formation by cell-surface, ITIM
      harboring Ig-like receptors. Modulation of these regulatory receptors may be a
      novel way to control various skeletal system disorders and inflammatory
      arthritis.

PMID- 18802078
TI  - Transplantation survival is maintained by granzyme B+ regulatory cells and
      adaptive regulatory T cells.
AB  - Granzyme B (GZB) has been implicated as an effector mechanism in regulatory T
      cells (T(reg)) suppression. In a model of T(reg)-dependent graft tolerance, it is
      shown that GZB- deficient mice are unable to establish long-term tolerance.
      Moreover, mice overexpressing the inhibitor of GZB, serine protease inhibitor 6,
      are also resistant to tolerization to alloantigen. Graft survival was shorter in
      bone marrow-mixed chimeras reconstituted with GZB-deficient T(reg) as compared
      with wild-type T(reg). Whereas there was no difference in graft survival in mixed
      chimeras reconstituted with wild-type, perforin-deficient, or Fas ligand
      deficient T(reg). Finally, data also show that if alloreactive effectors cannot
      express FoxP3 and be induced to convert in the presence of competent T(reg), then
      graft tolerance is lost. Our data are the first in vivo data to implicate GZB
      expression by T(reg) in sustaining long-lived graft survival.

PMID- 18802079
TI  - Two distinct T cell subsets, CD4+ and CD8+CD60+, and their cytokines are required
      for in vitro induction of human ragweed-specific memory IgE responses.
AB  - CD8(+)CD60(+) T cells (80-98% CD45RO(+); 20% CD23(+)) are significantly increased
      in the blood of serum IgE(+) ragweed-sensitized (RS) compared with serum IgE
      nonatopic humans (p = 0.001). CD8(+)CD60(+) T cells of the RS patients produced
      IL-2, IL-4, IL-10, IL-12, IFN-alpha. and IFN-gamma, but not IL-6 or IL-13. When
      their PBMC were cultured with ragweed Ag (RA), peak IgE responses occurred on day
      10; none was induced with non-cross-reacting or without Ag; nonatopic PBMC did
      not respond to any stimulant. When either CD4(+) or CD8(+)CD60(+) T cells were
      depleted from RS PBMC before culture with RA, no IgE responses were induced. If
      purified CD4(+) T cells or low numbers of CD8(+)CD60(+) T cells were added back
      to the depleted PBMC, IgE responses were restored. However, higher numbers of
      CD8(+)CD60(+) T cells totally suppressed IgE responses. Total suppression also
      was obtained when RS PBMC were cultured with RA and either anti-IL-2, IL-4, IL
      10, IL-12, IFN-gamma (all concentrations), or IFN-alpha (low concentrations), but
      not anti-IL-6 or IL-13. Higher concentrations of anti-IFN-alpha potentiated IgE
      responses.

PMID- 18802080
TI  - Impact of mammalian target of rapamycin inhibition on lymphoid homing and
      tolerogenic function of nanoparticle-labeled dendritic cells following allogeneic
      hematopoietic cell transplantation.
AB  - Dendritic cells (DC) play a major role in the pathogenesis of graft-vs-host
      disease (GvHD). Directed modification of surface molecules on DC that provide
      instructive signals for T cells may create a tolerogenic DC phenotype that
      affects GvHD severity. To investigate the impact of the mammalian target of
      rapamycin (mTOR) inhibitor rapamycin (RAPA) on in vivo migratory capacities,
      tolerogenic function, and B7 superfamily surface expression on DC following
      allogeneic hematopoietic cell transplantation (aHCT), we generated a platform for
      magnetic resonance imaging and bioluminescence imaging based cell trafficking
      studies. Luciferase transgenic DC were labeled with superparamagnetic iron oxide
      nanoparticles bound to a murine IgG Ab that allowed for Fc-gammaR-mediated
      endocytosis. Locally injected luc(+) DC could be tracked within their anatomical
      context by bioluminescence imaging and magnetic resonance imaging after aHCT,
      based on stable intracellular localization of superparamagnetic iron oxide-IgG
      complexes. RAPA preconditioned DC (DC-R) displayed reduced expression of MHC
      class II, B7-1 (CD80), and B7-2 (CD86) but not B7-H4 whose ligation of T cells
      has a profound inhibitory effect on their proliferation and cytokine secretion.
      DC-R of recipient genotype reduced GvHD severity that is compatible with their
      tolerogenic phenotype. CCR5, CCR7, and CD62L expression was not affected by mTOR
      inhibition, which allowed for DC-R in vivo trafficking to secondary lymphoid
      compartments where immunregulation is required. This study is the first to
      delineate the impact of RAPA on DC migration and tolerogenic function after aHCT.
      Modification of the DC phenotype by mTOR inhibition may have therapeutic
      potential in an attempt to reduce GvHD following aHCT.

PMID- 18802081
TI  - IL-33 induces antigen-specific IL-5+ T cells and promotes allergic-induced airway
      inflammation independent of IL-4.
AB  - Type 2 cytokines (IL-4, IL-5, and IL-13) play a pivotal role in helminthic
      infection and allergic disorders. CD4(+) T cells which produce type 2 cytokines
      can be generated via IL-4-dependent and -independent pathways. Although the IL-4
      dependent pathway is well documented, factors that drive IL-4-independent Th2
      cell differentiation remain obscure. We report here that the new cytokine IL-33,
      in the presence of Ag, polarizes murine and human naive CD4(+) T cells into a
      population of T cells which produce mainly IL-5 but not IL-4. This polarization
      requires IL-1R-related molecule and MyD88 but not IL-4 or STAT6. The IL-33
      induced T cell differentiation is also dependent on the phosphorylation of MAPKs
      and NF-kappaB but not the induction of GATA3 or T-bet. In vivo, ST2(-/-) mice
      developed attenuated airway inflammation and IL-5 production in a murine model of
      asthma. Conversely, IL-33 administration induced the IL-5-producing T cells and
      exacerbated allergen-induced airway inflammation in wild-type as well as IL-4(-/
      ) mice. Finally, adoptive transfer of IL-33-polarized IL-5(+)IL-4(-)T cells
      triggered airway inflammation in naive IL-4(-/-) mice. Thus, we demonstrate here
      that, in the presence of Ag, IL-33 induces IL-5-producing T cells and promotes
      airway inflammation independent of IL-4.

PMID- 18802082
TI  - Activation of invariant NKT cells ameliorates experimental ocular autoimmunity by
      a mechanism involving innate IFN-gamma production and dampening of the adaptive
      Th1 and Th17 responses.
AB  - Invariant NKT cells (iNKT cells) have been reported to play a role not only in
      innate immunity but also to regulate several models of autoimmunity. Furthermore,
      iNKT cells are necessary for the generation of the prototypic eye-related immune
      regulatory phenomenon, anterior chamber associated immune deviation (ACAID). In
      this study, we explore the role of iNKT cells in regulation of autoimmunity to
      retina, using a model of experimental autoimmune uveitis (EAU) in mice immunized
      with a uveitogenic regimen of the retinal Ag, interphotoreceptor retinoid-binding
      protein. Natural strain-specific variation in iNKT number or induced genetic
      deficiencies in iNKT did not alter baseline susceptibility to EAU. However, iNKT
      function seemed to correlate with susceptibility and its pharmacological
      enhancement in vivo by treatment with iNKT TCR ligands at the time of uveitogenic
      immunization reproducibly ameliorated disease scores. Use of different iNKT TCR
      ligands revealed dependence on the elicited cytokine profile. Surprisingly,
      superior protection against EAU was achieved with alpha-C-GalCer, which induces a
      strong IFN-gamma but only a weak IL-4 production by iNKT cells, in contrast to
      the ligands alpha-GalCer (both IFN-gamma and IL-4) and OCH (primarily IL-4). The
      protective effect of alpha-C-GalCer was associated with a reduction of adaptive
      Ag-specific IFN-gamma and IL-17 production and was negated by systemic
      neutralization of IFN-gamma. These data suggest that pharmacological activation
      of iNKT cells protects from EAU at least in part by a mechanism involving innate
      production of IFN-gamma and a consequent dampening of the Th1 as well as the Th17
      effector responses.

PMID- 18802083
TI  - Definition of APC presentation of phosphoantigen (E)-4-hydroxy-3-methyl-but-2
      enyl pyrophosphate to Vgamma2Vdelta 2 TCR.
AB  - Although microbial (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP) can
      activate primate Vgamma2Vdelta2 T cells, molecular mechanisms by which HMBPP
      interacts with Vgamma2Vdelta2 T cells remain poorly characterized. Here, we
      developed soluble, tetrameric Vgamma2Vdelta2 TCR of rhesus macaques to define
      HMBPP/APC interaction with Vgamma2Vdelta2 TCR. While exogenous HMBPP was
      associated with APC membrane in an appreciable affinity, the membrane-associated
      HMBPP readily bound to the Vgamma2Vdelta2 TCR tetramer. The Vgamma2Vdelta2 TCR
      tetramer was shown to bind stably to HMBPP presented on membrane by various APC
      cell lines from humans and nonhuman primates but not those from mouse, rat, or
      pig. The Vgamma2Vdelta2 TCR tetramer also bound to the membrane-associated HMBPP
      on primary monocytes, B cells and T cells. Consistently, endogenous
      phosphoantigen produced in Mycobacterium-infected dendritic cells was transported
      and presented on membrane, and bound stably to the Vgamma2Vdelta2 TCR tetramer.
      The capability of APC to present HMBPP for recognition by Vgamma2Vdelta2 TCR was
      diminished after protease treatment of APC. Thus, our studies elucidated an
      affinity HMBPP-APC association conferring stable binding to the Vgamma2Vdelta2
      TCR tetramer and the protease-sensitive nature of phosphoantigen presentation.
      The findings defined APC presentation of phosphoantigen HMBPP to Vgamma2Vdelta2
      TCR.

PMID- 18802084
TI  - Vaccination-induced systemic autoimmunity in farmed Atlantic salmon.
AB  - Over half of the salmon consumed globally are farm-raised. The introduction of
      oil-adjuvanted vaccines into salmon aquaculture made large-scale production
      feasible by preventing infections. The vaccines that are given i.p. contain oil
      adjuvant such as mineral oil. However, in rodents, a single i.p. injection of
      adjuvant hydrocarbon oil induces lupus-like systemic autoimmune syndrome,
      characterized by autoantibodies, immune complex glomerulonephritis, and
      arthritis. In the present study, whether the farmed salmon that received oil
      adjuvanted vaccine have autoimmune syndrome similar to adjuvant oil-injected
      rodents was examined. Sera and tissues were collected from vaccinated or
      unvaccinated Atlantic salmon (experimental, seven farms) and wild salmon.
      Autoantibodies (immunofluorescence, ELISA, and immunoprecipitation) and IgM
      levels (ELISA) in sera were measured. Kidneys and livers were examined for
      pathology. Autoantibodies were common in vaccinated fish vs unvaccinated controls
      and they reacted with salmon cells/Ags in addition to their reactivity with
      mammalian Ags. Diffuse nuclear/cytoplasmic staining was common in
      immunofluorescence but some had more specific patterns. Serum total IgM levels
      were also increased in vaccinated fish; however, the fold increase of
      autoantibodies was much more than that of total IgM. Sera from vaccinated fish
      immunoprecipitated ferritin and approximately 50% also reacted with other unique
      proteins. Thrombosis and granulomatous inflammation in liver, and immune-complex
      glomerulonephritis were common in vaccinated fish. Autoimmunity similar to the
      mouse model of adjuvant oil-induced lupus is common in vaccinated farmed Atlantic
      salmon. This may have a significant impact on production loss, disease of
      previously unknown etiology, and future strategies of vaccines and salmon
      farming.

PMID- 18802085
TI  - Protein kinase C theta regulates stability of the peripheral adhesion ring
      junction and contributes to the sensitivity of target cell lysis by CTL.
AB  - Destruction of virus-infected cells by CTL is an extremely sensitive and
      efficient process. Our previous data suggest that LFA-1-ICAM-1 interactions in
      the peripheral supramolecular activation cluster (pSMAC) of the immunological
      synapse mediate formation of a tight adhesion junction that might contribute to
      the sensitivity of target cell lysis by CTL. Herein, we compared more (CD8(+))
      and less (CD4(+)) effective CTL to understand the molecular events that promote
      efficient target cell lysis. We found that abrogation of the pSMAC formation
      significantly impaired the ability of CD8(+) but not CD4(+) CTL to lyse target
      cells despite having no effect of the amount of released granules by both CD8(+)
      and CD4(+) CTL. Consistent with this, CD4(+) CTL break their synapses more often
      than do CD8(+) CTL, which leads to the escape of the cytolytic molecules from the
      interface. CD4(+) CTL treatment with a protein kinase Ctheta inhibitor increases
      synapse stability and sensitivity of specific target cell lysis. Thus, formation
      of a stable pSMAC, which is partially controlled by protein kinase Ctheta,
      functions to confine the released lytic molecules at the synaptic interface and
      to enhance the effectiveness of target cell lysis.

PMID- 18802086
TI  - Bone marrow precursor cells from aged mice generate CD4 T cells that function
      well in primary and memory responses.
AB  - Understanding how aging impacts the function of memory CD4 T cells is critical
      for designing effective vaccines. Our studies show that immunological memory
      generated during youth functions well into old age, whereas that generated later
      in life functions poorly. This is the result of declines in the function of naive
      CD4 T cells from aged individuals and contributes to reduced efficacy of vaccines
      in the elderly. To begin to identify the cause of this defect, we examined the
      function of memory T cells generated from bone marrow precursor cells (BMPC) from
      young or aged mice in young hosts. In two different models, memory cells derived
      from young and aged BMPC exhibit good ex vivo and in vivo function. Importantly,
      memory CD4 T cells generated from aged BMPC exhibit potent cognate helper
      function for humoral responses, which are critical for effective immunization.
      These results indicate that there are no apparent age-related intrinsic defects
      in BMPC with regards to generation of functional memory T cells.

PMID- 18802087
TI  - NFATc1 regulates PD-1 expression upon T cell activation.
AB  - PD-1 is a transmembrane protein involved in the regulation of immunological
      tolerance. Multiple studies have reported an association between high levels of
      PD-1 expressed on T cell surfaces and exhaustion in lymphocyte populations when
      challenged by chronic viral infections, such as HIV. By using model systems
      consisting of murine EL4 cells, which constitutively express PD-1, and primary
      murine CD8 T cells that express PD-1 upon T cell stimulation, we have identified
      two tissue-specific hypersensitive sites at the 5' CR of the PD-1 locus. Gene
      reporter assays in CD8 T cells have shown that one of these sites has robust
      transcriptional activity in response to cell stimulation. Cell treatment with the
      calcineurin inhibitor cyclosporine A or a NFAT-specific inhibitor led to a sharp
      reduction in PD-1 expression in the constitutive and inducible systems.
      Furthermore, analysis of this region by chromatin immunoprecipitation assay
      revealed NFATc1 binding associated with gene activation in EL4 and primary CD8 T
      cells. Mutation of the NFATc1 binding site in PD-1 reporter constructs resulted
      in a complete loss of promoter activity. Together, these results demonstrate that
      PD-1 gene regulation occurs in part via the recruitment of NFATc1 to a novel
      regulatory element at the pdcd1 locus and provides the molecular mechanism
      responsible for the induction of PD-1 in response to T cell stimulation.

PMID- 18802088
TI  - Distinct regulation of integrin-dependent T cell conjugate formation and NF-kappa
      B activation by the adapter protein ADAP.
AB  - Following TCR stimulation, T cells utilize the hematopoietic specific adhesion
      and degranulation-promoting adapter protein (ADAP) to control both integrin
      adhesive function and NF-kappaB transcription factor activation. We have
      investigated the molecular basis by which ADAP controls these events in primary
      murine ADAP(-/-) T cells. Naive DO11.10/ADAP(-/-) T cells show impaired adhesion
      to OVAp (OVA aa 323-339)-bearing APCs that is restored following reconstitution
      with wild-type ADAP. Mutational analysis demonstrates that the central proline
      rich domain and the C-terminal domain of ADAP are required for rescue of T:APC
      conjugate formation. The ADAP proline-rich domain is sufficient to bind and
      stabilize the expression of SKAP55 (Src kinase-associated phosphoprotein of 55
      kDa), which is otherwise absent from ADAP(-/-) T cells. Interestingly, forced
      expression of SKAP55 in the absence of ADAP is insufficient to drive T:APC
      conjugate formation, demonstrating that both ADAP and SKAP55 are required for
      optimal LFA-1 function. Additionally, the ADAP proline-rich domain is required
      for optimal Ag-induced activation of CD69, CD25, and Bcl-x(L), but is not
      required for assembly of the CARMA1/Bcl10/Malt1 (caspase-recruitment domain
      (CARD) membrane-associated guanylate kinase (MAGUK) protein 1/B-cell CLL-lymphoma
      10/mucosa-associated lymphoid tissue lymphoma translocation protein 1) signaling
      complex and subsequent TCR-dependent NF-kappaB activity. Our results indicate
      that ADAP is used downstream of TCR engagement to delineate two distinct
      molecular programs in which the ADAP/SKAP55 module is required for control of
      T:APC conjugate formation and functions independently of ADAP/CARMA1-mediated NF
      kappaB activation.

PMID- 18802090
TI  - Disruption of allergenic activity of the major grass pollen allergen Phl p 2 by
      reassembly as a mosaic protein.
AB  - The recognition of conformational epitopes on respiratory allergens by IgE Abs is
      a key event in allergic inflammation. We report a molecular strategy for the
      conversion of allergens into vaccines with reduced allergenic activity, which is
      based on the reassembly of non-IgE-reactive fragments in the form of mosaic
      proteins. This evolution process is exemplified for timothy grass pollen-derived
      Phl p 2, a major allergen for more than 200 million allergic patients. In a first
      step, the allergen was disrupted into peptide fragments lacking IgE reactivity.
      cDNAs coding for these peptides were reassembled in altered order and expressed
      as a recombinant mosaic molecule. The mosaic molecule had lost the three
      dimensional structure, the IgE reactivity, and allergenic activity of the wild
      type allergen, but it induced high levels of allergen-specific IgG Abs upon
      immunization. These IgG Abs crossreacted with group 2 allergens from other grass
      species and inhibited allergic patients' IgE binding to the wild-type allergen.
      The mosaic strategy is a general strategy for the reduction of allergenic
      activity of protein allergens and can be used to convert harmful allergens into
      safe vaccines.

PMID- 18802089
TI  - T cell-dendritic cell immunological synapses contain TCR-dependent CD28-CD80
      clusters that recruit protein kinase C theta.
AB  - Short-lived TCR microclusters and a longer-lived protein kinase Ctheta-focusing
      central supramolecular activation cluster (cSMAC) have been defined in model
      immunological synapses (IS). In different model systems, CD28-mediated
      costimulatory interactions have been detected in microclusters, the cSMAC, or
      segregated from the TCR forming multiple distinct foci. The relationship between
      TCR and costimulatory molecules in the physiological IS of T cell-dendritic cell
      (DC) is obscure. To study the dynamic relationship of CD28-CD80 and TCR
      interactions in the T cell-DC IS during Ag-specific T cell activation, we
      generated CD80-eCFP mice using bacterial artificial chromosome transgenic
      technology. In splenic DCs, endogenous CD80 and CD80-eCFP localized to plasma
      membrane and Golgi apparatus, and CD80-eCFP was functional in vivo. In the OT-II
      T cell-DC IS, multiple segregated TCR, CD80, and LFA-1 clusters were detected. In
      the T cell-DC synapse CD80 clusters were colocalized with CD28 and PKCtheta, a
      characteristic of the cSMAC. Acute blockade of TCR signaling with anti-MHC Ab
      resulted in a rapid reduction in Ca(2+) signaling and the number and size of the
      CD80 clusters, a characteristic of TCR microclusters. Thus, the T cell-DC
      interface contains dynamic costimulatory foci that share characteristics of
      microclusters and cSMACs.

PMID- 18802091
TI  - Large scale mass spectrometric profiling of peptides eluted from HLA molecules
      reveals N-terminal-extended peptide motifs.
AB  - The majority of >2000 HLA class I molecules can be clustered according to
      overlapping peptide binding specificities or motifs recognized by CD8(+) T cells.
      HLA class I motifs are classified based on the specificity of residues located in
      the P2 and the C-terminal positions of the peptide. However, it has been
      suggested that other positions might be relevant for peptide binding to HLA class
      I molecules and therefore be used for further characterization of HLA class I
      motifs. In this study we performed large-scale sequencing of endogenous peptides
      eluted from K562 cells (HLA class I null) made to express a single HLA molecule
      from HLA-B*3501, -B*3502, -B*3503, -B*3504, -B*3506, or -B*3508. Using sequence
      data from >1,000 peptides, we characterized novel peptide motifs that include
      dominant anchor residues extending to all positions in the peptide. The length
      distribution of HLA-B35-bound peptides included peptides of up to 15 residues.
      Remarkably, we determined that some peptides longer than 11 residues represented
      N-terminal-extended peptides containing an appropriate HLA-B35 peptide motif.
      These results provide evidence for the occurrence of endogenous N-terminal
      extended peptide-HLA class I configurations. In addition, these results expand
      the knowledge about the identity of anchor positions in HLA class I-associated
      peptides that can be used for characterization of HLA class I motifs.

PMID- 18802092
TI  - The Pseudomonas toxin pyocyanin inhibits the dual oxidase-based antimicrobial
      system as it imposes oxidative stress on airway epithelial cells.
AB  - The dual oxidase-thiocyanate-lactoperoxidase (Duox/SCN(-)/LPO) system generates
      the microbicidal oxidant hypothiocyanite in the airway surface liquid by using
      LPO, thiocyanate, and Duox-derived hydrogen peroxide released from the apical
      surface of the airway epithelium. This system is effective against several
      microorganisms that infect airways of cystic fibrosis and other immunocompromised
      patients. We show herein that exposure of airway epithelial cells to Pseudomonas
      aeruginosa obtained from long-term cultures inhibits Duox1-dependent hydrogen
      peroxide release, suggesting that some microbial factor suppresses Duox activity.
      These inhibitory effects are not seen with the pyocyanin-deficient P. aeruginosa
      strain PA14 Phz1/2. We show that purified pyocyanin, a redox-active virulence
      factor produced by P. aeruginosa, inhibits human airway cell Duox activity by
      depleting intracellular stores of NADPH, as it generates intracellular
      superoxide. Long-term exposure of human airway (primary normal human bronchial
      and NCI-H292) cells to pyocyanin also blocks induction of Duox1 by Th2 cytokines
      (IL-4, IL-13), which was prevented by the antioxidants glutathione and N
      acetylcysteine. Furthermore, we showed that low concentrations of pyocyanin
      blocked killing of wild-type P. aeruginosa by the Duox/SCN(-)/LPO system on
      primary normal human bronchial epithelial cells. Thus, pyocyanin can subvert
      Pseudomonas killing by the Duox-based system as it imposes oxidative stress on
      the host. We also show that lactoperoxidase can oxidize pyocyanin, thereby
      diminishing its cytotoxicity. These data establish a novel role for pyocyanin in
      the survival of P. aeruginosa in human airways through competitive redox-based
      reactions between the pathogen and host.

PMID- 18802093
TI  - The varicellovirus UL49.5 protein blocks the transporter associated with antigen
      processing (TAP) by inhibiting essential conformational transitions in the 6+6
      transmembrane TAP core complex.
AB  - TAP translocates virus-derived peptides from the cytosol into the endoplasmic
      reticulum, where the peptides are loaded onto MHC class I molecules. This process
      is crucial for the detection of virus-infected cells by CTL that recognize the
      MHC class I-peptide complexes at the cell surface. The varicellovirus bovine
      herpesvirus 1 encodes a protein, UL49.5, that acts as a potent inhibitor of TAP.
      UL49.5 acts in two ways, as follows: 1) by blocking conformational changes of TAP
      required for the translocation of peptides into the endoplasmic reticulum, and 2)
      by targeting TAP1 and TAP2 for proteasomal degradation. At present, it is unknown
      whether UL49.5 interacts with TAP1, TAP2, or both. The contribution of other
      members of the peptide-loading complex has not been established. Using TAP
      deficient cells reconstituted with wild-type and recombinant forms of TAP1 and
      TAP2, TAP was defined as the prime target of UL49.5 within the peptide-loading
      complex. The presence of TAP1 and TAP2 was required for efficient interaction
      with UL49.5. Using deletion mutants of TAP1 and TAP2, the 6+6 transmembrane core
      complex of TAP was shown to be sufficient for UL49.5 to interact with TAP and
      block its function. However, UL49.5-induced inhibition of peptide transport was
      most efficient in cells expressing full-length TAP1 and TAP2. Inhibition of TAP
      by UL49.5 appeared to be independent of the presence of other peptide-loading
      complex components, including tapasin. These results demonstrate that UL49.5 acts
      directly on the 6+6 transmembrane TAP core complex of TAP by blocking essential
      conformational transitions required for peptide transport.

PMID- 18802094
TI  - Type I IFNs play a role in early resistance, but subsequent susceptibility, to
      the African trypanosomes.
AB  - Macrophages express a spectrum of proinflammatory and regulatory mediators during
      African trypanosomiasis. Microarray analyses revealed similar profiles of induced
      genes in macrophages stimulated with the trypanosome soluble variant surface
      glycoprotein in vitro and in macrophages taken from infected mice. Genes
      associated with the acute phase response and with type I IFN responses were
      prominent components of the macrophage activation profiles expressed within 72 h
      in vitro and in vivo. Thus, induction of proinflammatory gene expression is a
      characteristic of early trypanosome infection that is driven primarily by soluble
      variant surface glycoprotein exposure, and it may be that IFN-alpha/beta plays a
      central role in regulation of early resistance to trypanosomes. To test this
      hypothesis, we assessed parameters of infection in mouse strains with genetic
      alterations in the IFN-alpha/beta response pathway. We found that Ifnar1(-/-)
      mice, which lack the receptor for type I IFNs, exhibited delayed control of
      parasite burden during the first week of infection and died earlier than did wild
      type controls. However, infection of Ubp43(-/-) mice, which are hyperresponsive
      to type I IFNs, did not exhibit enhanced resistance to trypanosomes. Instead,
      these animals also failed to control parasite burden and were more susceptible
      than wild-type animals. Additionally, the Ubp43(-/-) mice exhibited a significant
      defect in IFN-gamma production, which is definitively linked to host resistance
      in trypanosomiasis. These results show that type I IFNs play a role in early
      control of parasites in infected mice but may contribute to down-regulation of
      IFN-gamma production and subsequent loss of host resistance later in infection.

PMID- 18802095
TI  - CD8 T cells utilize TRAIL to control influenza virus infection.
AB  - Elimination of influenza virus-infected cells during primary influenza virus
      infections is thought to be mediated by CD8(+) T cells though perforin- and FasL
      mediated mechanisms. However, recent studies suggest that CD8(+) T cells can also
      utilize TRAIL to kill virally infected cells. Therefore, we herein examined the
      importance of TRAIL to influenza-specific CD8(+) T cell immunity and to the
      control of influenza virus infections. Our results show that TRAIL deficiency
      increases influenza-associated morbidity and influenza virus titers, and that
      these changes in disease severity are coupled to decreased influenza-specific
      CD8(+) T cell cytotoxicity in TRAIL(-/-) mice, a decrease that occurs despite
      equivalent numbers of pulmonary influenza-specific CD8(+) T cells. Furthermore,
      TRAIL expression occurs selectively on influenza-specific CD8(+) T cells, and
      high TRAIL receptor (DR5) expression occurs selectively on influenza virus
      infected pulmonary epithelial cells. Finally, we show that adoptive transfer of
      TRAIL(+/+) but not TRAIL(-/-) CD8(+) effector T cells alters the mortality
      associated with lethal dose influenza virus infections. Collectively, our results
      suggest that TRAIL is an important component of immunity to influenza infections
      and that TRAIL deficiency decreases CD8(+) T cell-mediated cytotoxicity, leading
      to more severe influenza infections.

PMID- 18802096
TI  - Hepatitis C virus infection sensitizes human hepatocytes to TRAIL-induced
      apoptosis in a caspase 9-dependent manner.
AB  - Apoptosis of infected cells represents a key host defense mechanism against viral
      infections. The impact of apoptosis on the elimination of hepatitis C virus (HCV)
      infected cells is poorly understood. The TRAIL has been implicated in the death
      of liver cells in hepatitis-infected but not in normal liver cells. To determine
      the impact of TRAIL on apoptosis of virus-infected host cells, we studied TRAIL
      induced apoptosis in a tissue culture model system for HCV infection. We
      demonstrated that HCV infection sensitizes primary human hepatocytes and Huh7.5
      hepatoma cells to TRAIL induced apoptosis in a dose- and time-dependent manner.
      Mapping studies identified the HCV nonstructural proteins as key mediators of
      sensitization to TRAIL. Using a panel of inhibitors targeting different apoptosis
      pathways, we demonstrate that sensitization to TRAIL is caspase-9 dependent and
      mediated in part via the mitochondrial pathway. Sensitization of hepatocytes to
      TRAIL-induced apoptosis by HCV infection represents a novel antiviral host
      defense mechanism that may have important implications for the pathogenesis of
      HCV infection and may contribute to the elimination of virus-infected
      hepatocytes.

PMID- 18802097
TI  - Extracellular gelsolin binds lipoteichoic acid and modulates cellular response to
      proinflammatory bacterial wall components.
AB  - The various functions of gelsolin in extracellular compartments are not yet
      clearly defined but include actin scavenging and antiinflammatory effects.
      Gelsolin was recently reported to bind endotoxin (LPS) from various Gram-negative
      bacteria with high affinity. In this study we investigate whether gelsolin also
      interacts with bacterial wall molecules of Gram-positive bacteria such as
      lipoteichoic acid (LTA) and whether gelsolin's interaction with bacterial lipids
      from Gram-negative or Gram-positive bacteria affects their cellular inflammatory
      responses. A peptide based on the PPI binding site of gelsolin (160-169) binds
      purified LTA at the same molecular ratio that it binds phosphatidylinositol 4,5
      bisphosphate. The OD of recombinant human plasma gelsolin was found to decrease
      following the addition of purified LTA, and the binding of gelsolin to LTA
      inhibits F-actin depolymerization by gelsolin. Simultaneously, the ability of LTA
      to activate translocation of NF-kappaB, E-selectin expression, and adhesion of
      neutrophils to LTA-treated human aortic endothelial cells was compromised by
      gelsolin. Gelsolin was able to partially inhibit LPS- or LTA-induced release of
      IL-8 from human neutrophils but was unable to prevent Gram-positive Bacillus
      subtilis or Gram-negative Pseudomonas aeruginosa growth and had no effect on the
      antibacterial activity of the cathelicidin-derived antibacterial peptide LL37.
      These data suggest that extracellular gelsolin is involved in the host immune
      recognition of LTA or LPS following release of these molecules from the bacterial
      outer membrane during cell division or attack by drugs and immune components.

PMID- 18802098
TI  - Neutrophil elastase mediates innate host protection against Pseudomonas
      aeruginosa.
AB  - According to the widely accepted view, neutrophil elastase (NE), a neutrophil
      specific serine protease, is a major contributor to Pseudomonas aeruginosa
      infection-associated host tissue inflammation and damage, which in severe cases
      can lead to death. Herein, we provide for the first time compelling evidence that
      the host rather employs NE to protect itself against P. aeruginosa infection.
      Using a clinically relevant model of pneumonia, targeted deficiency in NE
      increased the susceptibility of mice to P. aeruginosa. We found that NE was
      required for maximal intracellular killing of P. aeruginosa by neutrophils. In
      investigating the mechanism of NE-mediated killing of P. aeruginosa, we found
      that NE degraded the major outer membrane protein F, a protein with important
      functions, including porin activity, maintenance of structural integrity, and
      sensing of host immune system activation. Consistent with this, the use of an
      isogenic mutant deficient in outer membrane protein F negated the role of NE in
      host defense against P. aeruginosa infection.

PMID- 18802099
TI  - Multifunctional, high-level cytokine-producing Th1 cells in the lung, but not
      spleen, correlate with protection against Mycobacterium tuberculosis aerosol
      challenge in mice.
AB  - Boosting bacillus Calmette-Guerin (BCG)-primed mice with a recombinant adenovirus
      expressing Mycobacterium tuberculosis Ag 85A by different administration routes
      has very different effects on protection against aerosol challenge with M.
      tuberculosis. Mice boosted intradermally make very strong splenic CD4 and CD8 Th1
      cytokine responses to Ag 85A, but show no change in lung mycobacterial burden
      over BCG primed animals. In contrast, intranasally boosted mice show greatly
      reduced mycobacterial burden and make a much weaker splenic response but a very
      strong lung CD4 and CD8 response to Ag 85A and an increased response to purified
      protein derivative. This effect is associated with the presence in the lung of
      multifunctional T cells, with high median fluorescence intensity and integrated
      median fluorescence intensity for IFN-gamma, IL-2, and TNF. In contrast, mice
      immunized with BCG alone have few Ag-specific cells in the lung and a low
      proportion of multifunctional cells, although individual cells have high median
      fluorescence intensity. Successful immunization regimes appear to induce Ag
      specific cells with abundant intracellular cytokine staining.

PMID- 18802100
TI  - IL-17 is a critical component of vaccine-induced protection against lung
      infection by lipopolysaccharide-heterologous strains of Pseudomonas aeruginosa.
AB  - In a murine model of acute fatal pneumonia, we previously showed that nasal
      immunization with a live-attenuated aroA deletant of Pseudomonas aeruginosa
      strain PAO1 elicited LPS serogroup-specific protection, indicating that opsonic
      Ab to the LPS O Ag was the most important immune effector. Because P. aeruginosa
      strain PA14 possesses additional virulence factors, we hypothesized that a live
      attenuated vaccine based on PA14 might elicit a broader array of immune
      effectors. Thus, an aroA deletant of PA14, denoted PA14DeltaaroA, was
      constructed. PA14DeltaaroA-immunized mice were protected against lethal pneumonia
      caused not only by the parental strain but also by cytotoxic variants of the O Ag
      heterologous P. aeruginosa strains PAO1 and PAO6a,d. Remarkably, serum from
      PA14DeltaaroA-immunized mice had very low levels of opsonic activity against
      strain PAO1 and could not passively transfer protection, suggesting that an
      antibody-independent mechanism was needed for the observed cross-serogroup
      protection. Compared with control mice, PA14DeltaaroA-immunized mice had more
      rapid recruitment of neutrophils to the airways early after challenge. T cells
      isolated from P. aeruginosa DeltaaroA-immunized mice proliferated and produced IL
      17 in high quantities after coculture with gentamicin-killed P. aeruginosa. Six
      hours following challenge, PA14DeltaaroA-immunized mice had significantly higher
      levels of IL-17 in bronchoalveolar lavage fluid compared with unimmunized,
      Escherichia coli-immunized, or PAO1DeltaaroA-immunized mice. Antibody-mediated
      depletion of IL-17 before challenge or absence of the IL-17 receptor abrogated
      the PA14DeltaaroA vaccine's protection against lethal pneumonia. These data show
      that IL-17 plays a critical role in antibody-independent vaccine-induced
      protection against LPS-heterologous strains of P. aeruginosa in the lung.

PMID- 18802101
TI  - Infection of myeloid dendritic cells with Listeria monocytogenes leads to the
      suppression of T cell function by multiple inhibitory mechanisms.
AB  - Myeloid dendritic cells (DC) and macrophages play an important role in pathogen
      sensing and antimicrobial defense. In this study we provide evidence that myeloid
      DC respond to infection with Listeria monocytogenes with simultaneous induction
      of multiple stimulatory and inhibitory molecules. However, the overall impact of
      infected DC during T cell encounter results in suppression of T cell activation,
      indicating that inhibitory pathways functionally predominate. Inhibitory activity
      of infected DC is effected mainly by IL-10 and cyclooxygenase 2-mediated
      mechanisms, with soluble CD25 acting as an IL-2 scavenger as well as by the
      products of tryptophan catabolism. These inhibitory pathways are strictly TNF
      dependent. In addition to direct infection, DC bearing this regulatory phenotype
      can be induced in vitro by a combination of signals including TNF, TLR2, and
      prostaglandin receptor ligation and by supernatants derived from the infected
      cells. Both infection-associated DC and other in vitro-induced regulatory DC are
      characterized by increased resistance to infection and enhanced bactericidal
      activity. Furthermore, myeloid DC expressing multiple regulatory molecules are
      identified in vivo in granuloma during listeriosis and tuberculosis. Based on the
      in vivo findings and the study of in vitro models, we propose that in
      granulomatous infections regulatory DC may possess dual function evolved to
      protect the host from disseminating infection via inhibition of granuloma
      destruction by T cells and control of pathogen spreading.

PMID- 18802102
TI  - Cathelicidin administration protects mice from Bacillus anthracis spore
      challenge.
AB  - Cathelicidins are a family of cationic peptides expressed in mammals that possess
      numerous bactericidal and immunomodulatory properties. In vitro analyses showed
      that human, mouse, and pig cathelicidins inhibited Bacillus anthracis bacterial
      growth at micromolar concentrations in the presence or absence of capsule.
      Combined in vitro analyses of the effects of each peptide on spore germination
      and vegetative outgrowth by time lapse phase contrast microscopy, transmission
      electron microscopy, and flow cytometric analysis showed that only the pig
      cathelicidin was capable of directly arresting vegetative outgrowth and killing
      the developing bacilli within the confines of the exosporium. C57BL/6 mice were
      protected from spore-induced death by each cathelicidin in a time- and dose
      dependent manner. Protection afforded by the porcine cathelicidin was due to its
      bactericidal effects, whereas the human and mouse cathelicidins appeared to
      mediate protection through increased recruitment of neutrophils to the site of
      infection. These findings suggest that cathelicidins might be utilized to augment
      the initial innate immune response to B. anthracis spore exposure and prevent the
      development of anthrax.

PMID- 18802103
TI  - Mast cells promote airway smooth muscle cell differentiation via autocrine up
      regulation of TGF-beta 1.
AB  - Asthma is a major cause of morbidity and mortality worldwide. It is characterized
      by airway dysfunction and inflammation. A key determinant of the asthma phenotype
      is infiltration of airway smooth muscle bundles by activated mast cells. We
      hypothesized that interactions between these cells promotes airway smooth muscle
      differentiation into a more contractile phenotype. In vitro coculture of human
      airway smooth muscle cells with beta-tryptase, or mast cells with or without
      IgE/anti-IgE activation, increased airway smooth muscle-derived TGF-beta1
      secretion, alpha-smooth muscle actin expression and agonist-provoked contraction.
      This promotion to a more contractile phenotype was inhibited by both the serine
      protease inhibitor leupeptin and TGF-beta1 neutralization, suggesting that the
      observed airway smooth muscle differentiation was driven by the autocrine release
      of TGF-beta1 in response to activation by mast cell beta-tryptase. Importantly,
      in vivo we found that in bronchial mucosal biopsies from asthmatics the intensity
      of alpha-smooth muscle actin expression was strongly related to the number of
      mast cells within or adjacent to an airway smooth muscle bundle. These findings
      suggest that mast cell localization in the airway smooth muscle bundle promotes
      airway smooth muscle cell differentiation into a more contractile phenotype, thus
      contributing to the disordered airway physiology that characterizes asthma.

PMID- 18802104
TI  - Platelet-activating factor production in the spinal cord of experimental allergic
      encephalomyelitis mice via the group IVA cytosolic phospholipase A2-lyso-PAFAT
      axis.
AB  - Platelet-activating factor (PAF; 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine)
      plays a critical role in inflammatory disorders including experimental allergic
      encephalomyelitis (EAE), an animal model for multiple sclerosis (MS). Although
      PAF accumulation in the spinal cord (SC) of EAE mice and cerebrospinal fluid of
      MS patients has been reported, little is known about the metabolic processing of
      PAF in these diseases. In this study, we demonstrate that the activities of
      phospholipase A(2) (PLA(2)) and acetyl-CoA:lyso-PAF acetyltransferase (LysoPAFAT)
      are elevated in the SC of EAE mice on a C57BL/6 genetic background compared with
      those of naive mice and correlate with disease severity. Correspondingly, levels
      of groups IVA, IVB, and IVF cytosolic PLA(2)s, group V secretory PLA(2), and
      LysoPAFAT transcripts are up-regulated in the SC of EAE mice. PAF acetylhydrolase
      activity is unchanged during the disease course. In addition, we show that
      LysoPAFAT mRNA and protein are predominantly expressed in microglia. Considering
      the substrate specificity and involvement of PAF production, group IVA cytosolic
      PLA(2) is likely to be responsible for the increased PLA(2) activity. These data
      suggest that PAF accumulation in the SC of EAE mice is profoundly dependent on
      the group IVA cytosolic PLA(2)/LysoPAFAT axis present in the infiltrating
      macrophages and activated microglia.

PMID- 18802105
TI  - Calcium/calmodulin-dependent protein kinase (CaMK) IV mediates nucleocytoplasmic
      shuttling and release of HMGB1 during lipopolysaccharide stimulation of
      macrophages.
AB  - The chromatin-binding factor high-mobility group box 1 (HMGB1) functions as a
      proinflammatory cytokine and late mediator of mortality in murine endotoxemia.
      Although serine phosphorylation of HMGB1 is necessary for nucleocytoplasmic
      shuttling before its cellular release, the protein kinases involved have not been
      identified. To investigate if calcium/calmodulin-dependent protein kinase (CaMK)
      IV serine phosphorylates and mediates the release of HMGB1 from macrophages
      (Mphi) stimulated with LPS, RAW 264.7 cells or murine primary peritoneal Mphi
      were incubated with either STO609 (a CaMKIV kinase inhibitor), KN93 (a CaMKIV
      inhibitor), or we utilized cells from which CaMKIV was depleted by RNA
      interference (RNAi) before stimulation with LPS. We also compared the LPS
      response of primary Mphi isolated from CaMKIV(+/+) and CaMKIV(-/-) mice. In both
      cell types LPS induced activation and nuclear translocation of CaMKIV, which
      preceded HMGB1 nucleocytoplasmic shuttling. However, Mphi treated with KN93,
      STO609, or CaMKIV RNAi before LPS showed reduced nucleocytoplasmic shuttling of
      HMGB1 and release of HMGB1 into the supernatant. Additionally, LPS induced serine
      phosphorylation of HMGB1, which correlated with an interaction between CaMKIV and
      HMGB1 and with CaMKIV phosphorylation of HMGB1 in vitro. In cells, both HMGB1
      phosphorylation and interaction with CaMKIV were inhibited by STO609 or CaMKIV
      RNAi. Similarly, whereas CaMKIV(+/+) Mphi showed serine phosphorylation of HMGB1
      in response to LPS, this phosphorylation was attenuated in CaMKIV(-/-) Mphi.
      Collectively, our results demonstrate that CaMKIV promotes the nucleocytoplasmic
      shuttling of HMGB1 and suggest that the process may be mediated through CaMKIV
      dependent serine phosphorylation of HMGB1.

PMID- 18802106
TI  - Secretogranin III directs secretory vesicle biogenesis in mast cells in a manner
      dependent upon interaction with chromogranin A.
AB  - Mast cells are granular immunocytes that reside in the body's barrier tissues.
      These cells orchestrate inflammatory responses. Proinflammatory mediators are
      stored in granular structures within the mast cell cytosol. Control of mast cell
      granule exocytosis is a major therapeutic goal for allergic and inflammatory
      diseases. However, the proteins that control granule biogenesis and abundance in
      mast cells have not been elucidated. In neuroendocrine cells, whose dense core
      granules are strikingly similar to mast cell granules, granin proteins regulate
      granulogenesis. Our studies suggest that the Secretogranin III (SgIII) protein is
      involved in secretory granule biogenesis in mast cells. SgIII is abundant in mast
      cells, and is organized into vesicular structures. Our results show that over
      expression of SgIII in mast cells is sufficient to cause an expansion of a
      granular compartment in these cells. These novel granules store inflammatory
      mediators that are released in response to physiological stimuli, indicating that
      they function as bona fide secretory vesicles. In mast cells, as in
      neuroendocrine cells, we show that SgIII is complexed with Chromogranin A (CgA).
      CgA is granulogenic when complexed with SgIII. Our data show that a novel non
      granulogenic truncation mutant of SgIII (1-210) lacks the ability to interact
      with CgA. Thus, in mast cells, a CgA-SgIII complex may play a key role in
      secretory granule biogenesis. SgIII function in mast cells is unlikely to be
      limited to its partnership with CgA, as our interaction trap analysis suggests
      that SgIII has multiple binding partners, including the mast cell ion channel
      TRPA1.

PMID- 18802107
TI  - Annexin A1 regulates intestinal mucosal injury, inflammation, and repair.
AB  - During mucosal inflammation, a complex array of proinflammatory and protective
      mechanisms regulates inflammation and severity of injury. Secretion of anti
      inflammatory mediators is a mechanism that is critical in controlling
      inflammatory responses and promoting epithelial restitution and barrier recovery.
      AnxA1 is a potent anti-inflammatory protein that has been implicated to play a
      critical immune regulatory role in models of inflammation. Although AnxA1 has
      been shown to be secreted in intestinal mucosal tissues during inflammation, its
      potential role in modulating the injury/inflammatory response is not understood.
      In this study, we demonstrate that AnxA1-deficient animals exhibit increased
      susceptibility to dextran sulfate sodium (DSS)-induced colitis with greater
      clinical morbidity and histopathologic mucosal injury. Furthermore, impaired
      recovery following withdrawal of DSS administration was observed in AnxA1 (-/-)
      animals compared with wild-type (WT) control mice that was independent of
      inflammatory cell infiltration. Since AnxA1 exerts its anti-inflammatory
      properties through stimulation of ALX/FPRL-1, we explored the role of this
      receptor-ligand interaction in regulating DSS-induced colitis. Interestingly,
      treatment with an ALX/FPRL-1 agonist, 15-epi-lipoxin A4 reversed the enhanced
      sensitivity of AnxA1 (-/-) mice to DSS colitis. In contrast, 15-epi-lipoxin A4
      did not significantly improve the severity of disease in WT animals.
      Additionally, differential expression of ALX/FPLR-1 in control and DSS-treated WT
      and AnxA1-deficient animals suggested a potential role for AnxA1 in regulating
      ALX/FPRL-1 expression under pathophysiological conditions. Together, these
      results support a role of endogenous AnxA1 in the protective and reparative
      properties of the intestinal mucosal epithelium.

PMID- 18802108
TI  - IFN consensus sequence binding protein (Icsbp) is critical for eosinophil
      development.
AB  - IFN consensus sequence binding protein (Icsbp) (IFN response factor-8) is a
      hematopoietic transcription factor with dual functions in myelopoiesis and
      immunity. In this study, we report a novel role of Icsbp in regulating the
      development of eosinophils. Loss of Icsbp in mice leads to a reduction of
      eosinophils in different tissues. During parasite infection with the nematode
      Nippostrongylus brasiliensis, Icsbp-deficient mice fail to mount eosinophilia
      despite a vigorous IL-5 response. Numbers of phenotypically defined eosinophil
      progenitors are decreased and those progenitors have, on a per-cell basis,
      reduced eosinophil differentiation potential. The transcription factor Gata1,
      crucial for eosinophil development, is reduced expressed in committed eosinophil
      progenitors in wells as mature eosinophils. These findings identify Icsbp as a
      novel transcription factor critical for the development of the eosinophil
      lineage.

PMID- 18802109
TI  - Immune cell activation by enterotoxin gene cluster (egc)-encoded and non-egc
      superantigens from Staphylococcus aureus.
AB  - The species Staphylococcus aureus harbors 19 superantigen gene loci, six of which
      are located in the enterotoxin gene cluster (egc). Although these egc
      superantigens are far more prevalent in clinical S. aureus isolates than non-egc
      superantigens, they are not a prominent cause of toxic shock. Moreover,
      neutralizing Abs against egc superantigens are very rare, even among carriers of
      egc-positive S. aureus strains. In search of an explanation, we have tested two
      non-exclusive hypotheses: 1) egc and non-egc superantigens have unique intrinsic
      properties and drive the immune system into different directions and 2) egc and
      non-egc superantigens are released by S. aureus under different conditions, which
      shape the immune response. A comparison of three egc (SEI, SElM, and SElO) and
      three non-egc superantigens (SEB, SElQ, and toxic shock syndrome toxin-1)
      revealed that both induced proliferation of human PBMC with comparable potency
      and elicited similar Th1/Th2-cytokine signatures. This was supported by gene
      expression analysis of PBMC stimulated with one representative superantigen from
      each group (SEI and SEB). They induced very similar transcriptional changes,
      especially of inflammation-associated gene networks, corresponding to a very
      strong Th1- and Th17-dominated immune response. In contrast, the regulation of
      superantigen release differed markedly between both superantigen groups. Egc
      encoded proteins were secreted by S. aureus during exponential growth, while non
      egc superantigens were released in the stationary phase. We conclude that the
      distinct biological behavior of egc and non-egc superantigens is not due to their
      intrinsic properties, which are very similar, but caused by their differential
      release by S. aureus.

PMID- 18802111
TI  - Evolution of the inflammatory response in vertebrates: fish TNF-alpha is a
      powerful activator of endothelial cells but hardly activates phagocytes.
AB  - TNF-alpha is conserved in all vertebrate classes and has been identified in all
      taxonomic groups of teleost fish. However, its biological activities and its role
      in infection are largely unknown. Using two complementary fish models, gilthead
      seabream and zebrafish, we report here that the main proinflammatory effects of
      fish TNF-alpha are mediated through the activation of endothelial cells. Thus,
      TNF-alpha promotes the expression of E-selectin and different CC and CXC
      chemokines in endothelial cells, thus explaining the recruitment and activation
      of phagocytes observed in vivo in both species. We also found that TLR ligands,
      and to some extent TNF-alpha, were able to increase the expression of MHC class
      II and CD83 in endothelial cells, which might suggest a role for fish endothelial
      cells and TNF-alpha in Ag presentation. Lastly, we found that TNF-alpha increases
      the susceptibility of the zebrafish to viral (spring viremia of carp virus) and
      bacterial (Streptococcus iniae) infections. Although the powerful actions of fish
      TNF-alpha on endothelial cells suggest that it might facilitate pathogen
      dissemination, it was found that TNF-alpha increased antiviral genes and, more
      importantly, had little effect on the viral load in early infection. In addition,
      the stimulation of ZF4 cells with TNF-alpha resulted in increased viral
      replication. Together, these results indicate that fish TNF-alpha displays
      different sorts of bioactivity to their mammalian counterparts and point to the
      complexity of the evolution that has taken place in the regulation of innate
      immunity by cytokines.

PMID- 18802110
TI  - STAT4 isoforms differentially regulate Th1 cytokine production and the severity
      of inflammatory bowel disease.
AB  - STAT4, a critical regulator of inflammation in vivo, can be expressed as two
      alternative splice forms, a full-length STAT4alpha, and a STAT4beta isoform
      lacking a C-terminal transactivation domain. Each isoform is sufficient to
      program Th1 development through both common and distinct subsets of target genes.
      However, the ability of these isoforms to mediate inflammation in vivo has not
      been examined. Using a model of colitis that develops following transfer of
      CD4(+) CD45RB(high) T cells expressing either the STAT4alpha or STAT4beta isoform
      into SCID mice, we determined that although both isoforms mediate inflammation
      and weight loss, STAT4beta promotes greater colonic inflammation and tissue
      destruction. This correlates with STAT4 isoform-dependent expression of TNF-alpha
      and GM-CSF in vitro and in vivo, but not Th1 expression of IFN-gamma or Th17
      expression of IL-17, which were similar in STAT4alpha- and STAT4beta-expressing T
      cells. Thus, higher expression of a subset of inflammatory cytokines from
      STAT4beta-expressing T cells correlates with the ability of STAT4beta-expressing
      T cells to mediate more severe inflammatory disease.

PMID- 18802112
TI  - Prostaglandin E2 exerts catabolic effects in osteoarthritis cartilage: evidence
      for signaling via the EP4 receptor.
AB  - Elevated levels of PGE(2) have been reported in synovial fluid and cartilage from
      patients with osteoarthritis (OA). However, the functions of PGE(2) in cartilage
      metabolism have not previously been studied in detail. To do so, we cultured
      cartilage explants, obtained from patients undergoing knee replacement surgery
      for advanced OA, with PGE(2) (0.1-10 muM). PGE(2) inhibited proteoglycan
      synthesis in a dose-dependent manner (maximum 25% inhibition (p < 0.01)). PGE(2)
      also induced collagen degradation, in a manner inhibitable by the matrix
      metalloproteinase (MMP) inhibitor ilomastat. PGE(2) inhibited spontaneous MMP-1,
      but augmented MMP-13 secretion by OA cartilage explant cultures. PCR analysis of
      OA chondrocytes treated with PGE(2) with or without IL-1 revealed that IL-1
      induced MMP-13 expression was augmented by PGE(2) and significantly inhibited by
      the cycolooygenase 2 selective inhibitor celecoxib. Conversely, MMP-1 expression
      was inhibited by PGE(2), while celecoxib enhanced both spontaneous and IL-1
      induced expression. IL-1 induction of aggrecanase 5 (ADAMTS-5), but not ADAMTS-4,
      was also enhanced by PGE(2) (10 muM) and reversed by celecoxib (2 muM).
      Quantitative PCR screening of nondiseased and end-stage human knee OA articular
      cartilage specimens revealed that the PGE(2) receptor EP4 was up-regulated in OA
      cartilage. Moreover, blocking the EP4 receptor (EP4 antagonist, AH23848) mimicked
      celecoxib by inhibiting MMP-13, ADAMST-5 expression, and proteoglycan
      degradation. These results suggest that PGE(2) inhibits proteoglycan synthesis
      and stimulates matrix degradation in OA chondrocytes via the EP4 receptor.
      Targeting EP4, rather than cyclooxygenase 2, could represent a future strategy
      for OA disease modification.

PMID- 18802114
TI  - Lipoteichoic acid induces HO-1 expression via the TLR2/MyD88/c-Src/NADPH oxidase
      pathway and Nrf2 in human tracheal smooth muscle cells.
AB  - Heme oxygenase (HO)-1 is a stress-inducible rate-limiting enzyme in heme
      degradation that confers cytoprotection against oxidative injury and provides a
      vital function in maintaining tissue homeostasis. Increasing reports have
      indicated that lipoteichoic acid (LTA) exerts as LPS as an immune system
      stimulating agent and plays a role in the pathogenesis of severe inflammatory
      responses induced by Gram-positive bacterial infection. We report that LTA is an
      inducer of HO-1 expression mediated through the signaling pathways in human
      tracheal smooth muscle cells (HTSMCs). LTA-induced HO-1 protein levels, mRNA
      expression, and promoter activity were attenuated by transfection with dominant
      negative mutants of TLR2 and MyD88, by pretreatment with the inhibitors of c-Src
      (PP1), NADPH oxidase (diphenylene iodonium chloride (DPI) and apocynin (APO)),
      and reactive oxygen species (ROS) scavenger (N-acetyl-l-cysteine) or by
      transfection with small interfering RNAs of Src and NF-E2-related factor 2
      (Nrf2). LTA-stimulated translocation of p47(phox) and Nrf2 or ROS production was
      attenuated by transfection with dominant negative mutants of TLR2, MyD88, and c
      Src and by pretreatment with DPI or APO. Furthermore, LTA-induced TLR2, MyD88,
      TNFR-associated factor (TRAF)6, c-Src, and p47(phox) complex formation was
      revealed by immunoprecipitation using an anti-TLR2 or anti-c-Src Ab followed by
      Western blot analysis against an anti-TLR2, anti-MyD88, anti-TRAF6, anti-c-Src,
      or anti-p47(phox) Ab. These results demonstrated that LTA-induced ROS generation
      was mediated through the TLR2/MyD88/TRAF6/c-Src/NADPH oxidase pathway, in turn
      initiates the activation of Nrf2, and ultimately induces HO-1 expression in
      HTSMCs.

PMID- 18802113
TI  - Lipopolysaccharide-induced expression of matrix metalloproteinases in human
      monocytes is suppressed by IFN-gamma via superinduction of ATF-3 and suppression
      of AP-1.
AB  - Matrix metalloproteinases (MMPs) are induced during inflammatory responses and
      are important for immune regulation, angiogenesis, wound healing, and tissue
      remodeling. Expression of MMPs needs to be tightly controlled to avoid excessive
      tissue damage. In this study, we investigated the regulation of MMP expression by
      inflammatory factors in primary human monocytes and macrophages. IFN-gamma, which
      augments inflammatory cytokine production in response to macrophage-activating
      factors such as TLR ligands, instead broadly suppressed TLR-induced MMP
      expression. Inhibition of MMP expression was dependent on STAT1 and required de
      novo protein synthesis. IFN-gamma strongly enhanced TLR-induced expression of the
      transcriptional repressor activating transcription factor (ATF-3) in a STAT1
      dependent manner, which correlated with recruitment of ATF-3 to the endogenous
      MMP-1 promoter as detected by chromatin immunoprecipitation assays. RNA
      interference experiments further supported a role for ATF-3 in suppression of MMP
      1 expression. In addition, IFN-gamma suppressed DNA binding by AP-1 transcription
      factors that are known to promote MMP expression and a combination of supershift,
      RNA interference and overexpression experiments implicated AP-1 family member Fra
      1 in the regulation of MMP-1 expression. These results define an IFN-gamma
      mediated homeostatic loop that limits the potential for tissue damage associated
      with inflammation, and identify transcriptional factors that regulate MMP
      expression in myeloid cells in inflammatory settings.

PMID- 18802115
TI  - Stimulatory role of lysophosphatidic acid in cyclooxygenase-2 induction by
      synovial fluid of patients with rheumatoid arthritis in fibroblast-like synovial
      cells.
AB  - While inflammatory cytokines are well-recognized critical factors for the
      induction of cyclooxygenase-2 (COX-2) in activated fibroblast-like synovial
      cells, the roles of biologically active components other than inflammatory
      cytokines in synovial fluid remain unknown. Herein, we assessed the role of
      lysophosphatidic acid (LPA), a pleiotropic lipid mediator, in COX-2 induction
      using synovial fluid of patients with rheumatoid arthritis (RA) in fibroblast
      like RA synovial cells. Synovial fluid from RA patients stimulated COX-2
      induction, which was associated with prostaglandin E(2) production, in RA
      synovial cells. The synovial fluid-induced actions were inhibited by G(i/o)
      protein inhibitor pertussis toxin and LPA receptor antagonist 3-(4-[4-([1-(2
      chlorophenyl)ethoxy]carbonyl amino)-3-methyl-5-isoxazolyl] benzylsulfanyl)
      propanoic acid (Ki16425). In fact, LPA alone significantly induced COX-2
      expression and enhanced IL-1alpha- or IL-1beta-induced enzyme expression in a
      manner sensitive to pertussis toxin and Ki16425. RA synovial cells abundantly
      expressed LPA(1) receptor compared with other LPA receptor subtypes. Moreover,
      synovial fluid contains a significant amount of LPA, an LPA-synthesizing enzyme
      autotaxin, and its substrate lysophosphatidylcholine. In conclusion, LPA existing
      in synovial fluid plays a critical role in COX-2 induction in collaboration with
      inflammatory cytokines in RA synovial cells. Ki16425-sensitive LPA receptors may
      be therapeutic targets for RA.

PMID- 18802116
TI  - Differential production of IL-23 and IL-12 by myeloid-derived dendritic cells in
      response to TLR agonists.
AB  - The recently delineated role for IL-23 in enhancing Th-17 activity suggests that
      regulation of its expression is distinct from that of IL-12. We hypothesized that
      independent TLR-mediated pathways are involved in the regulation of IL-12 and IL
      23 production by myeloid-derived dendritic cells (DCs). The TLR 2 ligand,
      lipoteichoic acid (LTA), the TLR 4 ligand, LPS, and the TLR 7/8 ligand,
      resimiquod (R848), induced production of IL-23 by DCs. None of these TLR ligands
      alone induced significant IL-12 production, except when combined with IFN-gamma
      or other TLR ligands. Notably, IL-23 production in response to single TLR ligands
      was inhibited by IL-4. DCs treated with single TLR agonists induced IL-17A
      production by allogeneic and Ag-specific memory CD4(+) T cells, an effect that
      was abrogated by IL-23 neutralization. Moreover, these DCs stimulated IL-17A
      production by tumor peptide-specific CD8(+) T cells. In contrast, DCs treated
      with dual signals induced naive and memory Th1 responses and enhanced the
      functional avidity of tumor-specific CD8(+) T cells. These results indicate that
      distinct microbial-derived stimuli are required to drive myeloid DC commitment to
      IL-12 or IL-23 production, thereby differentially polarizing T cell responses.

PMID- 18802117
TI  - Requirements for effective antitumor responses of TCR transduced T cells.
AB  - Adoptive transfer of TCR gene-modified T cells has been proposed as an attractive
      approach to target tumors for which it is difficult or impossible to induce
      strong tumor-specific T cell responses by vaccination. Whereas the feasibility of
      generating tumor Ag-specific T cells by gene transfer has been demonstrated, the
      factors that determine the in vivo effectiveness of TCR-modified T cells are
      largely unknown. We have analyzed the value of a number of clinically feasible
      strategies to enhance the antitumor potential of TCR modified T cells. These
      experiments reveal three factors that contribute greatly to the in vivo potency
      of TCR-modified T cells. First, irradiation-induced host conditioning is superior
      to vaccine-induced activation of genetically modified T cells. Second, increasing
      TCR expression through genetic optimization of TCR sequences has a profound
      effect on in vivo antitumor activity. Third, a high precursor frequency of TCR
      modified T cells within the graft is essential. Tumors that ultimately progress
      in animals treated with this optimized regimen for TCR-based adoptive cell
      transfer invariably display a reduced expression of the target Ag. This suggests
      TCR gene therapy can achieve a sufficiently strong selective pressure to warrant
      the simultaneous targeting of multiple Ags. The strategies outlined in this study
      should be of value to enhance the antitumor activity of TCR-modified T cells in
      clinical trials.

PMID- 18802118
TI  - Despite biased TRBV gene usage against a dominant HLA B57-restricted epitope, TCR
      diversity can provide recognition of circulating epitope variants.
AB  - The role of epitope-specific TCR repertoire diversity in the control of HIV-1
      viremia is unknown. Further analysis at the clonotype level is important for
      understanding the structural aspects of the HIV-1 specific repertoire that
      directly relate to CTL function and ability to suppress viral replication. In
      this study, we performed in-depth analysis of T cell clonotypes directed against
      a dominantly recognized HLA B57-restricted epitope (KAFSPEVIPMF; KF11) and
      identified common usage of the TCR beta-chain TRBV7 in eight of nine HLA B57
      subjects examined, regardless of HLA B57 subtype. Despite this convergent TCR
      gene usage, structural and functional assays demonstrated no substantial
      difference in functional or structural avidity between TRBV7 and non-TRBV7
      clonotypes and this epitopic peptide. In a subject where TRBV7-usage did not
      confer cross-reactivity against the dominant autologous sequence variant, another
      circulating TCR clonotype was able to preferentially recognize the variant
      peptide. These data demonstrate that despite selective recruitment of TCR for a
      conserved epitope over the course of chronic HIV-1 infection, TCR repertoire
      diversity may benefit the host through the ability to recognize circulating
      epitope variants.

PMID- 18802119
TI  - Gene expression profiling in autoimmune noninfectious uveitis disease.
AB  - Noninfectious uveitis is a predominantly T cell-mediated autoimmune, intraocular
      inflammatory disease. To characterize the gene expression profile from patients
      with noninfectious uveitis, PBMCs were isolated from 50 patients with clinically
      characterized noninfectious uveitis syndrome. A pathway-specific cDNA microarray
      was used for gene expression profiling and real-time PCR array for further
      confirmation. Sixty-seven inflammation- and autoimmune-associated genes were
      found differentially expressed in uveitis patients, with 28 of those genes being
      validated by real-time PCR. Several genes previously unknown for autoimmune
      uveitis, including IL-22, IL-19, IL-20, and IL-25/IL-17E, were found to be highly
      expressed among uveitis patients compared with the normal subjects with IL-22
      expression highly variable among the patients. Furthermore, we show that IL-22
      can affect primary human retinal pigment epithelial cells by decreasing total
      tissue resistance and inducing apoptosis possibly by decreasing phospho-Bad
      level. In addition, the microarray data identified a possible uveitis-associated
      gene expression pattern, showed distinct gene expression profiles in patients
      during periods of clinical activity and quiescence, and demonstrated similar
      expression patterns in related patients with similar clinical phenotypes. Our
      data provide the first evidence that a subset of IL-10 family genes are
      implicated in noninfectious uveitis and that IL-22 can affect human retinal
      pigment epithelial cells. The results may facilitate further understanding of the
      molecular mechanisms of autoimmune uveitis and other autoimmune originated
      inflammatory diseases.

PMID- 18802120
TI  - Human C3 deficiency associated with impairments in dendritic cell
      differentiation, memory B cells, and regulatory T cells.
AB  - Primary C3 deficiency, a rare autosomal inherited disease (OMIM 120700), was
      identified in a 2-year-old male suffering from recurrent pyogenic infections from
      early infancy with undetectable total complement hemolytic activity (CH50) and C3
      values. The nonconsanguineous parents and the two patients' two siblings had 50%
      normal serum C3 concentration. The molecular abnormality associated a paternal
      allele coding C3 with the missense mutation p.Ser(550)Pro and an apparently null
      maternal allele, with production of a defective protein that could no longer be
      secreted. Vaccination of the child did not induce a long-term Ab response.
      Accordingly, switched memory IgD(-)CD27(+) B cells were barely detected,
      amounting to only 2.3% of peripheral blood CD19(+) cells. Cells were
      significantly defective in stimulating alloreactive responses. The in vitro
      development of immature dendritic cells and their maturation capacity were
      greatly impaired, with decreased CD1a expression and IL-12p70 secretion ability.
      These cells were unable to induce autologous B cell proliferation and Ig
      secretion in the presence of CD40L and C3. Finally, the regulatory T cell
      development ability of CD4(+) T cells after CD3 and CD46 activation in the
      presence of IL-2 was significantly impaired. Thus, the association of important
      functional defects of dendritic cells, acquisition of B cell memory, and
      regulatory T cells with human C3 deficiency strongly supports a major role for C3
      in bridging innate and adaptive immunity in humans.

PMID- 18802121
TI  - YKL-40 is elevated in patients with chronic obstructive pulmonary disease and
      activates alveolar macrophages.
AB  - YKL-40 is a chitin-binding protein that is elevated in patients with various
      inflammatory conditions associated with ongoing remodeling. We investigated
      whether the levels of YKL-40 were up-regulated in the circulation and the airways
      of patients with chronic obstructive pulmonary disease (COPD), and whether it
      promoted the production of inflammatory mediators from macrophages. Serum,
      bronchoalveolar lavage (BAL), bronchial biopsies, lung tissue specimens, and
      alveolar macrophages from never-smokers (n = 15), smokers without COPD (n = 20),
      and smokers with COPD (n = 30) were assessed for YKL-40 levels and
      immunolocalization. In addition, YKL-40-induced mediator release from alveolar
      macrophages was examined. We found that smokers with COPD had elevated levels of
      YKL-40 in serum (p </= 0.027) and BAL (p </= 0.007), more YKL-40-positive cells
      in bronchial biopsies (p </= 0.03), and a greater proportion of alveolar
      macrophages expressing YKL-40 than smokers without COPD or never-smokers. YKL-40
      levels in serum and BAL were associated with airflow obstruction (pre-beta(2)
      agonist forced expiratory volume in 1 s, r(s) = -0.3892, p = 0.0072 and r(s) = 
      0.5491, p < 0.0001, respectively) and impaired diffusion lung capacity (transfer
      factor of the lung for carbon monoxide, r(s) = -0.4667, p = 0.002 and r(s) = 
      0.3854, p = 0.0045, respectively). TNF-alpha stimulated YKL-40 synthesis in
      alveolar macrophages from smokers with COPD, and exposure of these cells to YKL
      40 promoted the release of IL-8, MCP-1, MIP-1alpha, and metalloproteinase-9. We
      conclude that YKL-40 is up-regulated in COPD, in which it may contribute to
      tissue inflammation and remodeling by sustaining the synthesis of proinflammatory
      and fibrogenic chemokines and of metalloproteinases by alveolar macrophages.

PMID- 18802122
TI  - L2/3 interneuron groups defined by multiparameter analysis of axonal projection,
      dendritic geometry, and electrical excitability.
AB  - For a detailed description of the circuitry of cortical columns at the level of
      single neurons, it is essential to define the identities of the cell types that
      constitute these columns. For interneurons (INs), we described 4 "types of axonal
      projection patterns" in layer 2/3 (L2/3) with reference to the outlines of a
      cortical column (Helmstaedter et al. 2008a). In addition we quantified the
      dendritic geometry and electrical excitability of 3 types of the L2/3 INs:
      "local," "lateral," and "translaminar" inhibitors (Helmstaedter et al. 2008b).
      Here, we used an iterated cluster analysis (iCA) that combines axonal projection
      patterns with dendritic geometry and electrical excitability parameters to
      identify "groups" of INs, from a sample of 39 cells. The iCA defined 9 groups of
      INs. We propose a hierarchical scheme for identifying L2/3 INs. First, L2/3 INs
      can be classified as 4 types of axonal projections. Second, L2/3 INs can be
      subclassified as 9 groups with a high within-group similarity of dendritic,
      axonal, and electrical parameters. This scheme of identifying L2/3 INs may help
      to quantitatively describe inhibitory effects on sensory stimulus representations
      in L2/3 of cortical columns.

PMID- 18802123
TI  - Choice.
AB  - Understanding how and why analysands make the choices they do is central to both
      the clinical and the theoretical projects of psychoanalysis. And yet we know very
      little about the process of choice or about the relationship between choices and
      motives. A striking parallel is to be found between the ways choice is narrated
      in ancient Greek texts and the experience of analysts as they observe patients
      making choices in everyday clinical work. Pursuing this convergence of classical
      and contemporary sensibilities will illuminate crucial elements of the various
      meanings of choice, and of the way that these meanings change over the course of
      psychoanalytic treatment.

PMID- 18802124
TI  - An academic exchange on empathy.

PMID- 18802125
TI  - The language of empathy: an analysis of its constitution, development, and role
      in psychoanalytic listening.
AB  - Viewed from an epistemological perspective, empathy in psychoanalytic practice is
      described as that aspect of a specialized attentional stance that opens channels
      of interaction facilitating the formation of a trusting bond and enabling one to
      gain access to the emotional qualities of another's experience. A literature
      overview traces the origins of the concept in Freud and its role in
      psychoanalytic listening (including its controversial, divisive evolution in our
      field). Empathy is then examined from a semiotic-developmental framework. Its
      constitutional origins, differentiated forms, and distinctive purpose in clinical
      discourse are discussed. A developmental line is proposed, and clear distinctions
      are drawn between empathy in everyday life and its specialized technical
      application in clinical work.

PMID- 18802126
TI  - Some thoughts on empathy and countertransference.
AB  - Two aspects of countertransference-namely, the countertransference reaction and
      empathic understanding-must be distinguished. The term countertransference should
      be reserved exclusively for the conscious reactions of the analyst emerging from
      the preconscious by virtue of the patient's current transferences; the term
      empathy should be used to denote a perspective whereby the analyst employs
      current countertransference reactions for an understanding of the patient's inner
      life.

PMID- 18802127
TI  - Empathy, embodied simulation, and the brain: commentary on Aragno and
      Zepf/Hartmann.

PMID- 18802128
TI  - Iconic, indexical, and symbolic understanding: commentary on Aragno.

PMID- 18802131
TI  - Empathy and identification in Von Donnersmarck's The Lives of Others.
AB  - Florian Henckel von Donnersmarck's The Lives of Others, set in the German
      Democratic Republic in 1984, five years before the fall of the Berlin Wall, has
      been called the first accurate depiction of the psychological terror wielded by
      the Stasi, the East German secret police, who safeguarded the dictatorship of the
      proletariat. The film is about the psychological and political transformation of
      a Stasi officer, Wiesler, who undertakes the surveillance of a prominent
      playwright and his actress lover. The mechanisms through which Wiesler comes to
      empathize and identify with the subjects of his investigation, as he observes and
      listens in on the rich blend of passion, poetry, and politics that characterizes
      their lives, are explored in depth. Wiesler's transformation is based in part on
      the capacity to form implicit models of the behavior and experiences of others,
      based on the mirror neuron system, that Gallese and his colleagues call "embodied
      simulation." Underpinning the processes of empathy and identification so central
      to this film, embodied simulation is an unconscious and prereflexive mechanism
      through which the actions, emotions, and sensations we observe activate internal
      representations of the bodily and mental states of the other. Embodied simulation
      also expands our understanding of the power of the primal scene, which has long
      been identified as a major organizer of unconscious fantasies and conflicts
      throughout life, and which forms the central metaphor of the film. Embodied
      simulation scaffolds our aesthetic response to art, music, and literature,
      underlies the dynamics of spectatorship, and potentially catalyzes resistance to
      totalitarian mass movements.

PMID- 18802133
TI  - The comic in little Hans: literary conceit or analytic process? Commentary on
      Ahbel-Rappe.

PMID- 18802132
TI  - Freud's Little Oedipus: Hans as exception to the oedipal rule.
AB  - Freud's "The Analysis of a Phobia in a Five-Year-Old Boy" is regarded by Freud
      and by analytic readers and commentators as a prototype of his conception of the
      oedipus complex. A literary methodology is used to show that the interpretation
      of the oedipus complex at work in Freud's text in fact differs from Freud's
      standard view of it. While studying the paper as text, not as case report, may
      obscure or distort some clinical matters, it is valuable in that it makes legible
      a sort of theoretical unconscious in the text. In contrast to Freud's typically
      tragic view of the oedipus complex (in the tradition of ancient Greek tragedy),
      the Hans study evokes a comic vision (in the tradition of Greek New Comedy). This
      comic vision allows Hans a happy imaginative ending to the oedipal dilemma,
      challenges certain epistemic pretensions, and emphasizes the oedipus complex as a
      set of abiding existential questions. Given the deep link between Freud"s oedipus
      concept and a tragic view of human life, this departure in the Hans paper is a
      fascinating anomaly.

PMID- 18802135
TI  - Psychoanalytic developmental theory: a contemporary reconsideration.
AB  - Psychoanalytic developmental theory has never enjoyed a broad consensus among
      psychoanalytic thinkers. In today's postmodern era, its relevance and basic
      premises are even more in question as a legitimate part of psychoanalytic
      theorizing. Part of the problem has been (1) the serious errors perpetrated
      historically in the name of psychoanalytic developmental theory and (2) its
      current state of disarray in the wake of piecemeal efforts to rectify these
      errors. Nonetheless, its presence is discernible in every psychoanalyst's theory
      and clinical work, whether or not it is acknowledged or brought into a cohesive
      theoretical frame. The point of view of "intersubjective ego psychology"
      (Chodorow 2004), embraced by a growing number of analysts interested in
      development, offers a more flexible and inclusive paradigm for psychoanalytic
      developmental thinking in order to preserve its rightful place in contemporary
      psychoanalysis.

PMID- 18802136
TI  - Therapies in collision: introduction to Purcell.

PMID- 18802137
TI  - The analyst's attitude toward pharmacotherapy.
AB  - The increased acceptance of medication in psychoanalysis has occurred with too
      little consideration of possible complications. The potentially adverse
      psychological effects and disintegrative aspects of this important technical
      modification require further examination. While the use of phenomenologically
      defined diagnostic criteria provides valuable guidance to the clinician, the
      decision to include pharmacotherapy in a psychoanalysis must be understood also
      as a transference-countertransference enactment. The analyst's attitude toward
      pharmacotherapy is an essential element in some defensive and gratifying
      enactments, resistances that can interfere with psychoanalytic processes.
      Clinical material is presented illustrating narcissistic and perverse resistances
      that might be facilitated by analysts' attitudes toward pharmacotherapy,
      attitudes often tacitly communicated in decisions to use combined treatment.

PMID- 18802138
TI  - Presumed synergy or antagonism in combined treatment: commentary on Purcell.

PMID- 18802140
TI  - The uses of medications in psychoanalysis: what we know, what is uncertain. Panel
      reports.

PMID- 18802141
TI  - What can we learn from second analyses? Panel reports.

PMID- 18802142
TI  - Guilt. Panel reports.

PMID- 18802143
TI  - Analyst on the ropes: crises in treatment. Panel reports.

PMID- 18802144
TI  - High-dose methotrexate in osteosarcoma: let the questions surcease--time for
      final acceptance.

PMID- 18802145
TI  - Genomics of childhood leukemias: the virtue of complexity.

PMID- 18802146
TI  - Ectopic lymph nodes within human solid tumors.

PMID- 18802147
TI  - Osteoporosis in men with prostate cancer: now for the fracture data.

PMID- 18802148
TI  - Raising the profile of cancer of unknown primary.

PMID- 18802149
TI  - Gene expression signatures predictive of early response and outcome in high-risk
      childhood acute lymphoblastic leukemia: A Children's Oncology Group Study
      [corrected].
AB  - PURPOSE: To identify children with acute lymphoblastic leukemia (ALL) at initial
      diagnosis who are at risk for inferior response to therapy by using molecular
      signatures. PATIENTS AND METHODS: Gene expression profiles were generated from
      bone marrow blasts at initial diagnosis from a cohort of 99 children with
      National Cancer Institute-defined high-risk ALL who were treated uniformly on the
      Children's Oncology Group (COG) 1961 study. For prediction of early response,
      genes that correlated to marrow status on day 7 were identified on a training set
      and were validated on a test set. An additional signature was correlated with
      long-term outcome, and the predictive models were validated on three large,
      independent patient cohorts. Results We identified a 24-probe set signature that
      was highly predictive of day 7 marrow status on the test set (P = .0061).
      Pathways were identified that may play a role in early blast regression. We have
      also identified a 47-probe set signature (which represents 41 unique genes) that
      was predictive of long-term outcome in our data set as well as three large
      independent data sets of patients with childhood ALL who were treated on
      different protocols. However, we did not find sufficient evidence for the added
      significance of these genes and the derived predictive models when other known
      prognostic features, such as age, WBC, and karyotype, were included in a
      multivariate analysis. CONCLUSION: Genes and pathways that play a role in early
      blast regression may identify patients who may be at risk for inferior responses
      to treatment. A fully validated predictive gene expression signature was defined
      for high-risk ALL that provided insight into the biologic mechanisms of treatment
      failure.

PMID- 18802150
TI  - Results of the EICESS-92 Study: two randomized trials of Ewing's sarcoma
      treatment--cyclophosphamide compared with ifosfamide in standard-risk patients
      and assessment of benefit of etoposide added to standard treatment in high-risk
      patients.
AB  - PURPOSE: The European Intergroup Cooperative Ewing's Sarcoma Study investigated
      whether cyclophosphamide has a similar efficacy as ifosfamide in standard-risk
      (SR) patients and whether the addition of etoposide improves survival in high
      risk (HR) patients. PATIENTS AND METHODS: SR patients (localized tumors, volume
      <100 mL) were randomly assigned to receive four courses of vincristine,
      dactinomycin, ifosfamide, and doxorubicin (VAIA) induction therapy followed by 10
      courses of either VAIA or vincristine, dactinomycin, cyclophosphamide, and
      doxorubicin (VACA; cyclophosphamide replacing ifosfamide). HR patients (volume
      >or=100 mL or metastases) were randomly assigned to receive 14 courses of either
      VAIA or VAIA plus etoposide (EVAIA). Outcome measures were event-free survival
      (EFS; defined as the time to first recurrence, progression, second malignancy, or
      death) and overall survival (OS). RESULTS: A total of 647 patients were randomly
      assigned: 79 SR patients were assigned to VAIA, 76 SR patients were assigned to
      VACA, 240 HR were assigned to VAIA, and 252 HR patients were assigned to EVAIA.
      The median follow-up was 8.5 years. In the SR group, the hazard ratios (VACA v
      VAIA) for EFS and OS were 0.91 (95% CI, 0.55 to 1.53) and 1.08 (95% CI, 0.58 to
      2.03), respectively. There was a higher incidence of hematologic toxicities in
      the VACA arm. In the HR group, the EFS and OS hazard ratios (EVAIA v VAIA)
      indicated a 17% reduction in the risk of an event (95% CI, -35% to 5%; P = .12)
      and 15% reduction in dying (95% CI, -34% to 10%), respectively. The effect seemed
      greater among patients without metastases (hazard ratio = 0.79; P = .16) than
      among those with metastases (hazard ratio = 0.96; P = .84). CONCLUSION:
      Cyclophosphamide seemed to have a similar effect on EFS and OS as ifosfamide in
      SR patients but was associated with increased toxicity. In HR patients, the
      addition of etoposide seemed to be beneficial.

PMID- 18802151
TI  - Phase I study of weekly oxaliplatin in relapsed or refractory pediatric solid
      malignancies.
AB  - PURPOSE: To explore feasibility, maximum-tolerated dose (MTD), and recommended
      dose (RD) for phase II studies of weekly oxaliplatin for the treatment of
      relapsed or refractory pediatric solid malignancies. PATIENTS AND METHODS:
      Eligible patients were 6 months to 21 years old, had a diagnosis of a solid
      malignancy, and had experienced treatment failure with at least two or more
      previous lines of therapy. The phase I study was multicentric, open-label, and
      nonrandomized. It foresaw two phases: a dose-escalation phase (comprising six
      levels) to find the RD and an extension at the RD to evaluate the cumulative
      toxicity. Oxaliplatin was administered intravenously over 2 hours on days 1, 8,
      and 15 of a 28-day cycle. RESULTS: Forty-five patients were enrolled: 29 patients
      in the dose-escalation phase and 16 patients in the extension at the RD. Median
      age was 9.5 years (range, 2.8 to 20.0 years) and 7.8 years (range, 1.8 to 19.2
      years), respectively. The dose-limiting toxicities during the first treatment
      cycle were grade 3 (G3) sepsis at 50 mg/m(2), G3 dysesthesia at 90 mg/m(2), and
      G3 dysesthesia and G3 paresthesia at 110 mg/m(2), thus the MTD and RD was 90
      mg/m(2). No case of ototoxicity was reported. Stable disease was reported in
      seven patients (16.3%), and confirmed partial response was observed in two
      patients (4.7%), one with neuroblastoma and one with osteosarcoma. CONCLUSION:
      Oxaliplatin administered in a weekly schedule has an acceptable safety profile,
      different from cisplatin and carboplatin, and shows activity in children with
      relapsed or refractory solid tumors, suggesting further investigation in
      pediatric malignancies.

PMID- 18802152
TI  - Medical care in long-term survivors of childhood cancer: a report from the
      childhood cancer survivor study.
AB  - PURPOSE: To evaluate whether childhood cancer survivors receive regular medical
      care focused on the specific morbidities that can arise from their therapy.
      PATIENTS AND METHODS: We conducted a cross-sectional survey of health care use in
      8,522 participants in the Childhood Cancer Survivor Study, a multi-institutional
      cohort of childhood cancer survivors. We assessed medical visits in the preceding
      2 years, whether these visits were related to the prior cancer, whether survivors
      received advice about how to reduce their long-term risks, and whether screening
      tests were discussed or ordered. Completion of echocardiograms and mammograms
      were assessed in patients at high risk for cardiomyopathy or breast cancer. We
      examined the relationship between demographics, treatment, health status, chronic
      medical conditions, and health care use. RESULTS: Median age at cancer diagnosis
      was 6.8 years (range, 0 to 20.9 years) and at interview was 31.4 years (range,
      17.5 to 54.1 years). Although 88.8% of survivors reported receiving some form of
      medical care, only 31.5% reported care that focused on their prior cancer
      (survivor-focused care), and 17.8% reported survivor-focused care that included
      advice about risk reduction or discussion or ordering of screening tests. Among
      survivors who received medical care, those who were black, older at interview, or
      uninsured were less likely to have received risk-based, survivor-focused care.
      Among patients at increased risk for cardiomyopathy or breast cancer, 511 (28.2%)
      of 1,810 and 169 (40.8%) of 414 had undergone a recommended echocardiogram or
      mammogram, respectively. CONCLUSION: Despite a significant risk of late effects
      after cancer therapy, the majority of childhood cancer survivors do not receive
      recommended risk-based care.

PMID- 18802153
TI  - Long-term survival for patients with non-small-cell lung cancer with intratumoral
      lymphoid structures.
AB  - PURPOSE: It has been established that the immune system plays an important role
      in tumor rejection. There is also compelling evidence that immune responses can
      develop independently of secondary lymphoid organs in tertiary lymphoid
      structures. We studied the presence and the correlation of tertiary lymphoid
      structures with clinical outcome in non-small-cell lung cancer (NSCLC), as the
      prognostic value of these structures in patients with cancer had not yet been
      established. PATIENTS AND METHODS: This retrospective study was performed by
      immunohistochemistry on paraffin-embedded tissue specimens from 74 patients with
      early-stage NSCLC. RESULTS: Tertiary lymphoid structures were detected in some
      tumors but not in nontumoral lungs. Thus we called these structures tumor-induced
      bronchus-associated lymphoid tissue (Ti-BALT). As in lymph nodes, Ti-BALTs were
      composed of mature dendritic cell (DC)/T-cell clusters adjacent to B-cell
      follicles and had features of an ongoing immune response. Because the
      quantitative counting of Ti-BALT was difficult to achieve, we used mature DCs
      that homed exclusively in Ti-BALT as a specific marker of these structures.
      Univariate analysis showed that the density of mature DCs was highly associated
      with a favorable clinical outcome (overall, disease-specific, and disease-free
      survival), suggesting that Ti-BALT may participate in antitumoral immunity. The
      density of tumor-infiltrating lymphocytes, in particular, CD4(+) and T-bet(+) Th1
      T cells, was profoundly decreased in tumors weakly infiltrated by mature DCs.
      CONCLUSION: The density of mature DCs was found to be a better predictor of
      clinical outcome than the other parameters tested. The number of tumor
      infiltrating mature DCs may identify patients with early-stage NSCLC who have a
      high risk of relapse.

PMID- 18802154
TI  - Induction of immune responses and clinical efficacy in a phase II trial of IDM
      2101, a 10-epitope cytotoxic T-lymphocyte vaccine, in metastatic non-small-cell
      lung cancer.
AB  - PURPOSE: Generation of broad cytotoxic T-lymphocyte responses against multiple
      epitopes and tumor-associated antigens (TAAs) may provide effective immunotherapy
      in patients with cancer. We evaluated a single-vial peptide vaccine consisting of
      nine HLA-A2 supertype-binding epitopes (two native and seven analog epitopes
      modified for optimal HLA binding or T-cell receptor stimulation) covering five
      TAAs and the universal helper pan-DR epitope, formulated as a stable emulsion
      with incomplete Freund's adjuvant (Montanide ISA 51; Seppic SA, Paris, France).
      The clinical efficacy, safety, and multiepitope immunogenicity of IDM-2101 was
      evaluated in patients with stage IIIB or IV non-small-cell lung cancer (NSCLC).
      PATIENTS AND METHODS: A total of 63 patients were enrolled who were positive for
      HLA-A2. End points included survival, safety, and immune response. IDM-2101
      (previously EP-2101) was administered every 3 weeks for the first 15 weeks, then
      every 2 months through year 1, then quarterly through year 2, for a total of 13
      doses. Epitope-specific cytotoxic and helper T-lymphocyte immunogenic responses
      were measured by the interferon gamma enzyme-linked immunosorbent spot assay.
      RESULTS: No significant adverse events were noted. Low-grade erythema and pain at
      the injection site were the most common adverse effects. One-year survival in the
      treated patients was 60%, and median survival was 17.3 months. One complete and
      one partial response were identified. Survival was longer in patients
      demonstrating an immune response to epitope peptides (P < .001). CONCLUSION: IDM
      2101 was well tolerated, and evidence of efficacy was suggested.

PMID- 18802155
TI  - Skeletal health after continuation, withdrawal, or delay of alendronate in men
      with prostate cancer undergoing androgen-deprivation therapy.
AB  - PURPOSE: Androgen-deprivation therapy (ADT) for prostate cancer is associated
      with bone loss and osteoporotic fractures. Our objective was to examine changes
      in bone density and turnover with sustained, discontinued, or delayed oral
      bisphosphonate therapy in men receiving ADT. PATIENTS AND METHODS: A total of 112
      men with nonmetastatic prostate cancer receiving ADT were randomly assigned to
      alendronate 70 mg once weekly or placebo in a double-blind, partial-crossover
      trial with a second random assignment at year 2 for those who initially received
      active therapy. Outcomes included bone mineral density and bone turnover markers.
      RESULTS: Men initially randomly assigned to alendronate and randomly reassigned
      at year 2 to continue had additional bone density gains at the spine (mean, 2.3%
      +/- 0.7) and hip (mean, 1.3% +/- 0.5%; both P < .01); those randomly assigned to
      placebo in year 2 maintained density at the spine and hip but lost (mean, -1.9%
      +/- 0.6%; P < .01) at the forearm. Patients randomly assigned to begin
      alendronate in year 2 experienced improvements in bone mass at the spine and hip,
      but experienced less of an increase compared with those who initiated alendronate
      at baseline. Men receiving alendronate for 2 years experienced a mean 6.7% (+/-
      1.2%) increase at the spine and a 3.2% (+/- 1.5%) at the hip (both P < .05). Bone
      turnover remained suppressed. CONCLUSION: Among men with nonmetastatic prostate
      cancer receiving ADT, once-weekly alendronate improves bone density and decreases
      turnover. A second year of alendronate provides additional skeletal benefit,
      whereas discontinuation results in bone loss and increased bone turnover. Delay
      in bisphosphonate therapy appears detrimental to bone health.

PMID- 18802156
TI  - Gene expression profiling to identify the histogenetic origin of metastatic
      adenocarcinomas of unknown primary.
AB  - PURPOSE: Patients with adenocarcinoma of unknown primary origin (ACUP) constitute
      approximately 4% of all malignancies. For effective treatment of these patients,
      it is considered optimal to identify the primary tumor origins. Currently, the
      success rate of the diagnostic work-up is only 20% to 30%. Our goal was to
      evaluate the contribution of gene expression profiling for routine clinical
      practice in patients with ACUP. PATIENTS AND METHODS: Formalin-fixed, paraffin
      embedded (FFPE) samples were obtained from 84 patients with a known primary
      adenocarcinoma and from 38 patients with ACUP. An extensive immunohistochemical
      panel classified 16 of the patients with ACUP, whereas 22 patients remained
      unclassified for their histogenetic origin. Information about staging procedures
      and clinical follow-up were available in all patient cases. The expression data
      were analyzed in relation to clinicopathologic variables and immunohistochemical
      results. RESULTS: The gene expression-based assay classified the primary site
      correctly in 70 (83%) of 84 patient cases of primary and metastatic tumors of
      known origin, with good sensitivity for the majority of the tumor classes and
      relatively poor sensitivity for primary lung adenocarcinoma. Gene expression
      profiling identified 15 (94%) of 16 patients with initial ACUP who were
      classified by immunohistochemistry, and it made a valuable contribution to a
      potential site of origin in 14 of the 22 patients with ACUP. CONCLUSION: The gene
      expression platform can classify correctly from FFPE samples the majority of
      tumors classes both in patients with known primary and in patients with ACUP.
      Therefore, gene expression profiling represents an additional analytic approach
      to assist with the histogenetic diagnosis of patients with ACUP.

PMID- 18802157
TI  - Molecular profiling of carcinoma of unknown primary and correlation with clinical
      evaluation.
AB  - PURPOSE: To evaluate the feasibility of a 10-gene reverse transcriptase
      polymerase chain reaction assay to identify the tissue of origin in patients with
      carcinoma of unknown primary (CUP) site. PATIENTS AND METHODS: Diagnostic biopsy
      formalin-fixed, paraffin-embedded (FFPE) specimens from 120 patients with CUP
      were collected retrospectively from Sarah Cannon Research Institute, Nashville,
      TN, and prospectively from The University of Texas M. D. Anderson Cancer Center,
      Houston, TX. Tissue of origin assignments by the assay were correlated with
      clinical and pathologic features and with response to therapy. RESULTS: The assay
      was successfully performed in 104 patients (87%), and a tissue of origin was
      assigned in 63 patients (61%). In the remaining 41 patients (39%), the molecular
      profiles were not specific for the six tumor types detectable by this assay. The
      tissues of origin most commonly identified were lung, pancreas, and colon; most
      of these patients had clinical and pathologic features consistent with these
      diagnoses. Patients with lung and pancreas profiles had poor response to
      treatment. Patients with colon cancer profiles had better response to colon
      cancer-specific therapies than they did to empiric CUP therapy with
      taxane/platinum regimens. Patients with ovarian cancer profiles were atypical,
      with widespread visceral metastases and a paucity of overt peritoneal
      involvement. CONCLUSION: This gene expression profiling assay was feasible using
      FFPE biopsy specimens and identified a putative tissue of origin in 61% of
      patients with CUP. In most patients, the assigned tissue of origin was compatible
      with clinicopathologic features and response to treatment. Prospective studies in
      which assay results are used to direct therapy are indicated.

PMID- 18802158
TI  - Identification of cancer care and protocol characteristics associated with
      recruitment in breast cancer clinical trials.
AB  - PURPOSE: It is estimated that only 5% of patients with cancer participate in a
      clinical trial. Barriers to participation may relate to available protocols,
      physicians, and patients, but few data exist on barriers related to cancer care
      environments and protocol characteristics. METHODS: The primary objective was to
      identify characteristics of cancer care environments and clinical trial protocols
      associated with a low recruitment into breast cancer clinical trials. Secondary
      objectives were to determine yearly recruitment fraction onto clinical trials
      from 1997 to 2002 in Ontario, Canada, and to compare recruitment fraction among
      years. Questionnaires were sent to hospitals requesting characteristics of cancer
      care environments and to cooperative groups/pharmaceutical companies for
      information on protocols and the number of patients recruited per hospital/year.
      Poisson regression was used to estimate the recruitment fraction. RESULTS:
      Questionnaire completion rate varied between 69% and 100%. Recruitment fraction
      varied between 5.4% and 8.5% according to year. More than 30% of patients were
      diagnosed in hospitals with no available trials. In multivariate analysis, the
      following characteristics were associated with recruitment: use of placebo versus
      not (relative risk [RR] = 0.80; P = .05), nonmetastatic versus metastatic trial
      (RR = 2.80; P < .01), and for nonmetastatic trials, protocol allowing an interval
      of 12 weeks or longer versus less than 12 weeks (from diagnosis, surgery, or end
      of therapy) before enrollment (RR = 1.36; P < .01). CONCLUSION: Allowable
      interval of 12 weeks or longer to randomly assign patients in clinical trials
      could help recruitment. In our study, absence of an available clinical trial
      represented the largest barrier to recruitment.

PMID- 18802159
TI  - Causes of fecal and urinary incontinence after total mesorectal excision for
      rectal cancer based on cadaveric surgery: a study from the Cooperative Clinical
      Investigators of the Dutch total mesorectal excision trial.
AB  - PURPOSE: Total mesorectal excision (TME) for rectal cancer may result in
      anorectal and urogenital dysfunction. We aimed to study possible nerve disruption
      during TME and its consequences for functional outcome. Because the levator ani
      muscle plays an important role in both urinary and fecal continence, an
      explanation could be peroperative damage of the nerve supply to the levator ani
      muscle. METHODS: TME was performed on cadaver pelves. Subsequently, the anatomy
      of the pelvic floor innervation and its relation to the pelvic autonomic
      innervation and the mesorectum were studied. Additionally, data from the Dutch
      TME trial were analyzed to relate anorectal and urinary dysfunction to possible
      nerve damage during TME procedure. RESULTS: Cadaver TME surgery demonstrated
      that, especially in low tumors, the pelvic floor innervation can be damaged.
      Furthermore, the origin of the levator ani nerve was located in close proximity
      of the origin of the pelvic splanchnic nerves. Analysis of the TME trial data
      showed that newly developed urinary and fecal incontinence was present in 33.7%
      and 38.8% of patients, respectively. Both types of incontinence were
      significantly associated with each other (P = .027). Low anastomosis was
      significantly associated with urinary incontinence (P = .049). One third of the
      patients with newly developed urinary and fecal incontinence also reported
      difficulty in bladder emptying, for which excessive perioperative blood loss was
      a significant risk factor. CONCLUSION: Perioperative damage to the pelvic floor
      innervation could contribute to fecal and urinary incontinence after TME,
      especially in case of a low anastomosis or damage to the pelvic splanchnic
      nerves.

PMID- 18802160
TI  - Prospective relationships of physical activity with quality of life among
      colorectal cancer survivors.
AB  - PURPOSE: Physical activity can enhance quality of life for cancer survivors.
      However, few longitudinal studies have examined whether physical activity has a
      sustained effect on improvements in quality of life. The present study aims to
      examine the relationships between physical activity and quality of life over 2
      years after a colorectal cancer diagnosis. PATIENTS AND METHODS: Data were
      collected within the Colorectal Cancer and Quality of Life Study, in which 1,966
      people diagnosed with colorectal cancer were recruited through the Queensland
      Cancer Registry. Participants completed telephone interviews at approximately 6,
      12, and 24 months after diagnosis. Generalized linear mixed models were used to
      estimate the overall, interindividual, and intraindividual level independent
      effects of participation in physical activity on quality of life. RESULTS: There
      was an overall independent association between physical activity and quality of
      life. At a given time point, participants achieving at least 150 minutes of
      physical activity per week had an 18% higher quality of life score than those who
      reported no physical activity. Significant associations were also present at the
      interindividual level (differences between participants) and intraindividual
      level (within participant changes). CONCLUSION: These findings suggest that the
      positive association between physical activity and quality of life is consistent
      over time. Encouraging colorectal cancer survivors to be physically active may be
      a helpful strategy for enhancing quality of life.

PMID- 18802162
TI  - Blogging during terminal care: communication, color schemes, and creating a
      community.

PMID- 18802161
TI  - Randomized controlled trial of collaborative care management of depression among
      low-income patients with cancer.
AB  - PURPOSE: To determine the effectiveness of the Alleviating Depression Among
      Patients With Cancer (ADAPt-C) collaborative care management for major depression
      or dysthymia. PATIENTS AND METHODS: Study patients included 472 low-income,
      predominantly female Hispanic patients with cancer age >or= 18 years with major
      depression (49%), dysthymia (5%), or both (46%). Patients were randomly assigned
      to intervention (n = 242) or enhanced usual care (EUC; n = 230). Intervention
      patients had access for up to 12 months to a depression clinical specialist
      (supervised by a psychiatrist) who offered education, structured psychotherapy,
      and maintenance/relapse prevention support. The psychiatrist prescribed
      antidepressant medications for patients preferring or assessed to require
      medication. RESULTS: At 12 months, 63% of intervention patients had a 50% or
      greater reduction in depressive symptoms from baseline as assessed by the Patient
      Health Questionnaire-9 (PHQ-9) depression scale compared with 50% of EUC patients
      (odds ratio [OR] = 1.98; 95% CI, 1.16 to 3.38; P = .01). Improvement was also
      found for 5-point decrease in PHQ-9 score among 72.2% of intervention patients
      compared with 59.7% of EUC patients (OR = 1.99; 95% CI, 1.14 to 3.50; P = .02).
      Intervention patients also experienced greater rates of depression treatment
      (72.3% v 10.4% of EUC patients; P < .0001) and significantly better quality-of
      life outcomes, including social/family (adjusted mean difference between groups,
      2.7; 95% CI, 1.22 to 4.17; P < .001), emotional (adjusted mean difference, 1.29;
      95% CI, 0.26 to 2.22; P = .01), functional (adjusted mean difference, 1.34; 95%
      CI, 0.08 to 2.59; P = .04), and physical well-being (adjusted mean difference,
      2.79; 95% CI, 0.49 to 5.1; P = .02). CONCLUSION: ADAPt-C collaborative care is
      feasible and results in significant reduction in depressive symptoms, improvement
      in quality of life, and lower pain levels compared with EUC for patients with
      depressive disorders in a low-income, predominantly Hispanic population in public
      sector oncology clinics.

PMID- 18802163
TI  - Intracranial granulocytic sarcoma after chemotherapy for pineal germinoma and
      testicular cancer.

PMID- 18802164
TI  - Splenic marginal zone lymphoma: transformation to diffuse large B-cell lymphoma
      with isolated cerebral manifestation.

PMID- 18802165
TI  - Complete remission of psoriasis after autologous hematopoietic stem-cell
      transplantation for multiple myeloma.

PMID- 18802166
TI  - Epithelial atypia: a marker risk of concomitant or subsequent breast carcinoma?

PMID- 18802167
TI  - Patient age and comorbidity are major determinants of adjuvant chemotherapy use
      for stage III colon cancer in routine clinical practice.

PMID- 18802168
TI  - Non-Hodgkin's lymphoma in patients with glioma treated with temozolomide.

PMID- 18802169
TI  - From bench to bedside: a case of rapid reversal of bortezomib-induced neuropathic
      pain by the TRPM8 activator, menthol.

PMID- 18802170
TI  - Treatment considerations for gallbladder cancer should include extent of surgery.

PMID- 18802171
TI  - Prediction model for adjuvant radiation therapy for gallbladder cancer: not ready
      to be used.

PMID- 18802172
TI  - Impact of immediate postoperative death on the estimation of a survival benefit
      from postoperative radiation therapy for cancer of the gallbladder.

PMID- 18802173
TI  - Revisiting the politics of dangerousness.

PMID- 18802174
TI  - Mandated community treatment: applying leverage to achieve adherence.

PMID- 18802175
TI  - Clinical practice guidelines as learned treatises: understanding their use as
      evidence in the courtroom.
AB  - It is important for forensic experts to understand how clinical practice
      guidelines may enter the courtroom, what role they may play in a trial, and how
      they relate to expert testimony. Guidelines enter the record in several different
      ways and in several types of cases, typically with the assistance of an expert
      witness. A common vehicle for their introduction is the learned-treatise
      exception to the hearsay rule. Case law before and after Daubert v. Merrell Dow
      Pharmaceuticals, Inc. helps to elucidate the scrutiny that courts may direct
      toward medical texts proffered as evidence. This article discusses the
      implications of different rules and relevant case law for the forensic
      psychiatrist. The discussion notes important considerations for the expert
      witness, such as how guidelines may affect the expert's role, concerns about the
      reliability and relevance of scientific evidence, and questions about whether
      guidelines will be used for inculpatory or exculpatory purposes in medical
      malpractice trials.

PMID- 18802176
TI  - Commentary: when is a practice guideline only a guideline?
AB  - Clinical Practice Guidelines (CPGs) have been promulgated by a variety of sources
      with differing goals: professional societies, state and federal governmental
      bodies, third-party payers such as insurers and HMOs, and hospitals. Compliance
      rates by practitioners are modest at best so that their use as standards of care
      for "usual and customary" practice is questionable. Some states are experimenting
      with the use of CPGs as a requirement for malpractice coverage.

PMID- 18802177
TI  - Commentary: Helling v. Carey, Caveat Medicus.
AB  - Forensic experts should be aware of the increasing importance of clinical
      practice guidelines (CPGs) in various legal settings. CPGs are a type of learned
      treatise and are accepted into court proceedings under hearsay exception
      provisions. The courts now use CPGs as shorthand for the standard of care in
      making malpractice determinations. However, medical guidelines can function as a
      sword or a shield in the courtroom arena. The Helling v. Carey medical
      malpractice case serves as a frightful reminder of the potential consequences of
      allowing courts to craft their own standards of medical care.

PMID- 18802178
TI  - Forensic applications of cerebral single photon emission computed tomography in
      mild traumatic brain injury.
AB  - Traumatic brain injury (TBI) is a substantial source of mortality and morbidity
      world wide. Although most such injuries are relatively mild, accurate diagnosis
      and prognostication after mild TBI are challenging. These problems are
      complicated further when considered in medicolegal contexts, particularly civil
      litigation. Cerebral single photon emission computed tomography (SPECT) may
      contribute to the evaluation and treatment of persons with mild TBI. Cerebral
      SPECT is relatively sensitive to the metabolic changes produced by TBI. However,
      such changes are not specific to this condition, and their presence on cerebral
      SPECT imaging does not confirm a diagnosis of mild TBI. Conversely, the absence
      of abnormalities on cerebral SPECT imaging does not exclude a diagnosis of mild
      TBI, although such findings may be of prognostic value. The literature does not
      demonstrate consistent relationships between SPECT images and neuropsychological
      testing or neuropsychiatric symptoms. Using the rules of evidence shaped by
      Daubert v. Merrell Dow Pharmaceuticals, Inc., and its progeny to analyze the
      suitability of SPECT for forensic purposes, we suggest that expert testimony
      regarding SPECT findings should be admissible only as evidence to support
      clinical history, neuropsychological test results, and structural brain imaging
      findings and not as stand-alone diagnostic data.

PMID- 18802179
TI  - Commentary: Applications of functional neuroimaging to civil litigation of mild
      traumatic brain injury.
AB  - The current definition of mild traumatic brain injury (MTBI) is in flux.
      Presently, there are at least three working definitions of this disorder in the
      United States, with no clear consensus. Functional neuroimaging, such as single
      photon emission computed tomography (SPECT) and positron emission tomography
      (PET), initially showed promise in their ability to improve the diagnostic
      credibility of MTBI. Over the past decade, that promise has not been fulfilled
      and there is a paucity of quality studies or standards for the application of
      functional neuroimaging to traumatic brain injury, particularly in litigation.
      The legal profession is ahead of the science in this matter. The emergence of
      neurolaw is driving a growing use of functional neuroimaging, as a sole imaging
      modality, used by lawyers in an attempt to prove MTBI at trial. The medical
      literature on functional neuroimaging and its applications to MTBI is weak
      scientifically, sparse in quality publications, lacking in well-designed
      controlled studies, and currently does not meet the complete standards of Daubert
      v. Merrell Dow Pharmaceuticals, Inc., for introduction of scientific evidence at
      trial. At the present time, there is a clear lack of clinical correlation between
      functional neuroimaging of MTBI and behavioral, neuropsychological, or structural
      neuroimaging deficits. The use of SPECT or PET, without concurrent clinical
      correlation with structural neuroimaging (CT or MRI), is not recommended to be
      offered as evidence of MTBI in litigation.

PMID- 18802180
TI  - The conditional release of insanity acquittees: three decades of decision-making.
AB  - The problem with the practical application of decision-making regarding release
      of mentally ill defenders lies in the inherently ambiguous definitions of mental
      illness and dangerousness, both of which are necessary for the continued
      commitment of insanity acquittees. In this study, we examined how clinicians make
      release decisions in a forensic facility, with particular attention paid to how
      such decision-making may have changed over time. Records were reviewed to
      determine documented criteria indicating readiness for release. The results
      indicated that compliance and treatment response were the primary reasons that
      the patients were judged ready for release. In addition, increasing attention to
      the use of substances as a risk factor was evident in the records, with
      substantially more documentation found in the most recent decade. Our data
      suggest that clinicians view three concerns to be of primary import when making
      release decisions: responsiveness to and compliance with the treatment, substance
      use, and risk of violence.

PMID- 18802181
TI  - Commentary: Biases that affect the decision to conditionally release an insanity
      acquittee.
AB  - The care and management of hospitalized insanity acquittees can be quite
      challenging. As patients progress in treatment, clinicians must invariably
      address whether the patient is ready to be returned to the community, balancing
      the liberty interests of the acquittee with the protection of society. The
      process by which this determination is made is far from simple and involves
      review of clinical interview and collateral information, identification of
      indicators of outcome post-discharge, and the use of structured risk assessment
      instruments. The decision to release an acquittee conditionally is also
      influenced by an array of factors that emanate from within the clinician, within
      the institution, the mental health system, the courts, and the broader society.
      While such biases affect a clinician's objectivity, they are also a natural part
      of the evaluation process. Their identification is essential so that the degree
      to which such biases influence the conditional release decision can be more fully
      understood and addressed.

PMID- 18802182
TI  - Conceptualizing and characterizing accuracy in assessments of competence to stand
      trial.
AB  - This article describes a mathematical framework for conceptualizing the accuracy
      of forensic experts' opinions on competence to stand trial (CST) and explains how
      an expert's expressed opinion about CST can be decomposed into four elements: (1)
      contextual requirements of the defendant (determined partly by the defendant's
      past actions) that lie outside the defendant's future control; (2) personal
      attributes of the defendant that are relevant to competence; (3) the expert's
      intrinsic ability to distinguish competent from incompetent defendants; and (4)
      the expert's wish to favor or avoid certain types of outcomes (e.g., a preference
      to avoid seeing an incompetent defendant stand trial for a serious charge).
      Because experts are imperfect and have varying levels of confidence in their
      opinions, one can describe the accuracy of CST assessments by using receiver
      operating characteristic (ROC) analysis. The article describes some types of
      insights one might derive from ROC analyses of CST assessments if experts, at
      least for research purposes, expressed opinions as graded levels of confidence.
      Although no satisfactory gold standard exists for establishing the truth about a
      defendant's competence, statistical methods developed over the past two decades
      may allow investigators to make inferences about the diagnostic accuracy of
      experts' CST assessments.

PMID- 18802183
TI  - Commentary: Facts and values in competency assessment.
AB  - Dr. Mossman's article cogently describes an approach to measuring the accuracy of
      competency-to-stand-trial assessments in the presence of a gold standard. I argue
      that a gold standard may not exist. A conclusion as to whether a defendant is fit
      to proceed requires a trade-off between a range of desired ends. This trade-off
      is inevitably influenced by the values of the examiner.

PMID- 18802184
TI  - Making consent more informed: preliminary results from a multiple-choice test
      among probation-referred marijuana users entering a randomized clinical trial.
AB  - Although individuals who use illicit drugs are a potentially vulnerable
      population, there have been no objective evaluations of the effectiveness of
      standard informed consent procedures in assuring that prospective participants
      entering drug abuse treatment trials fully understand the nature of the research
      and treatments in which they have agreed to participate. Young, marijuana
      dependent adults referred by the criminal justice system who were enrolling in a
      randomized treatment trial were asked to complete a multiple-choice quiz
      concerning basic elements of the trial before providing written informed consent.
      Participants were assigned to standard drug counseling or motivational
      interviewing/skills-building therapy, delivered alone or with incentives for
      attending sessions and submitting marijuana-free urine specimens. Only 55 percent
      of the 130 participants correctly answered all four questions, and 20 percent
      incorrectly answered a question concerning their right to refuse to participate.
      An unexpected finding was that quiz scores were modestly associated with
      marijuana use outcome measures. These preliminary findings highlight the
      importance of systematically evaluating the understanding of research
      participants, particularly those in vulnerable populations, of their rights and
      key aspects of the trials in which they agree to participate.

PMID- 18802185
TI  - Emotional responses of staff to assault in a pediatric state hospital.
AB  - In this study, we examined the emotional responses of staff to patient-on-staff
      assault at a state inpatient psychiatric hospital for children and adolescents.
      Staff (n = 93) completed self-report measures assessing general psychiatric
      functioning and symptoms of depression and anxiety. Staff assaulted by patients
      in the past six months (n = 59) were compared with those who had not been
      assaulted (n = 34). Direct-care staff were more likely to be assaulted than were
      other staff. Assaulted staff were more likely to report prior nonsexual assault
      by a stranger, higher anxiety, more somatic concerns, greater vulnerability and
      lack of control, and higher levels of impairment at work and were more likely to
      consider terminating employment than were non-assaulted staff. Our cross
      sectional data suggest several differences in assaulted versus non-assaulted
      staff. Further studies are needed to determine whether differences in anxiety and
      traumatic events precede assaults or represent antecedent risk factors for being
      assaulted.

PMID- 18802186
TI  - A national analysis of medical licensure applications.
AB  - The 1990 enactment of the Americans With Disabilities Act (ADA) and subsequent
      case law have established that medical board screening of physician licensure
      applicants for histories of mental illness or substance use may constitute
      discrimination. This study examines how physician licensure questionnaires have
      evolved since the enactment of the ADA. Specifically, we requested medical
      licensure applications in 2006 from all U.S. affiliated medical licensing boards
      (n = 54) and analyzed their mental health and substance use inquiries
      comparatively with application data from 1993, 1996, and 1998. Response rates
      were 96 percent (n = 52) for initial registration applications and 93 percent (n
      = 50) for renewal applications. Our results indicate that applicants in 2006,
      compared with applicants in the 1990s, were questioned more about past, rather
      than current, histories of mental illness and substance use. These findings
      revealed medical board practices that seem to run counter to existing court
      interpretations of the ADA as well as licensure guidelines established by several
      professional organizations.

PMID- 18802187
TI  - Defining mental disorder when it really counts: DSM-IV-TR and SVP/SDP statutes.
AB  - Civil commitment under the sexually violent predator (SVP) statutes requires the
      presence of a statutorily defined diagnosed mental disorder linked to sexual
      offending. As a consequence of broad statutory definitions and ambiguously
      written court decisions, a bright line separating an SVP mental disorder from
      ordinary criminal behavior is difficult to draw. Some forensic evaluators reject
      whole categories of DSM-IV-TR (Diagnostic and Statistical Manual of Mental
      Disorders: Text Revision) diagnoses as qualifying disorders (e.g., personality
      and substance abuse disorders), while others debate whether recurrent rape
      constitutes a paraphilic disorder. We argue that the ramifications of the SVP
      process, in representing both the balancing of public safety and the protection
      of an individual's right to liberty, demand that decisions about what is a
      legally defined mental disorder not be made in an arbitrary and idiosyncratic
      manner. Greater clarity and standardization must come from both sides: the
      legalists who interpret the law and the clinicians who apply and work under it.

PMID- 18802188
TI  - Crime and punishment: is "justice" good public policy?
AB  - Dysfunctional features of American penology are mitigated somewhat by the
      application (though uneven) of modern science. Unfortunately, these advances do
      not address major flaws in the ideas on which the system is erected. These
      include retribution, proportional punishment, and all-or-none notions of criminal
      responsibility. We propose abandoning retribution for its own sake; making
      punishment proportional to its effectiveness for behavior change rather than to
      the indignation evoked by the offense; and incorporating punishment into
      sentences based on the clinical and behavioral characteristics of the offender,
      including containment as necessary for public safety. Every offender would be
      held responsible, but the meaning and consequences thereof would change. The
      proposed changes could only occur incrementally. New systems of oversight and
      accountability would be required. Legislative bodies could provide guidelines,
      and courts could oversee, but neither could micromanage. Few are better qualified
      to work toward these goals than readers of this journal.

PMID- 18802189
TI  - Template for quickly creating forensic psychiatry reports.
AB  - Great variability exists in written forensic psychiatry reports. A template is
      offered for quick preparation of such reports. The template includes the standard
      elements of competency and criminal responsibility reports. The method makes use
      of currently available computer technology.

PMID- 18802190
TI  - Testimony by mentally ill individuals.
AB  - Integration of individuals with mental illness into the community equates their
      status with that of the general population, and they may be called to give
      testimony concerning an incident witnessed, or a crime committed that they were
      not involved in, to admit guilt to a crime, or to testify about a crime in which
      they were the victim. Four case descriptions are presented: complaints against
      family, complaints against staff, abuse in treatment, and sexual abuse. The
      Israeli courts ruled that the testimony of a mentally ill person is admissible;
      however, the question that arises is the degree of importance that should be
      attributed to it. In 2005, a law was passed in Israel concerning the
      investigation and testimonial processes of individuals with intellectual or
      mental handicaps. Clinicians may sometimes be the link between the patient and
      the complex legal system; thus, they must be alert and attentive to the patients
      and advocate for them when necessary.

PMID- 18802191
TI  - When judges practice psychiatry.

PMID- 18802192
TI  - Attacks on the British royal family.

PMID- 18802193
TI  - Gun law legislation.

PMID- 18802194
TI  - Use of the term "mental defective" by Congress and in the U.S. Code.

PMID- 18802195
TI  - The crafting of legislation.

PMID- 18802196
TI  - Circulating oxidized LDL: determinants and association with brachial flow
      mediated dilation.
AB  - Circulating oxidized LDL (oxLDL) levels are strongly correlated to LDL
      cholesterol (LDL-c) and apolipoprotein-B100 (apoB100), making it difficult to
      disentangle their independent contributions to cardiovascular risk. We explored
      the determinants of oxLDL and the relation between oxLDL and flow-mediated
      dilation (FMD) of the brachial artery to investigate whether the oxLDL/LDL-c and
      oxLDL/apoB100 ratios are more informative than the separate variables. FMD of the
      brachial artery and plasma concentrations of oxLDL, LDL-cholesterol, and apoB100
      were measured in 624 men and women (age range 50 to 87 years), participating in a
      population-based cohort study. OxLDL was strongly correlated with apoB100 (r =
      0.82, P < 0.001) and LDL-c (r = 0.67, P < 0.001). Other major independent
      determinants of oxLDL were sex, HDL-cholesterol, and LDL particle size. LDL-c and
      apoB100 concentrations were not significantly associated with FMD. After
      adjustment for age, sex, glucose tolerance status, and Framingham risk score, the
      oxLDL/apoB100 ratio was negatively related to FMD (P = 0.017). This association
      was weaker for the oxLDL/ LDL-c ratio (P = 0.062) and absent for oxLDL level (P =
      0.27). In contrast to oxLDL, the oxLDL/apoB100 ratio, and to a lesser extent the
      oxLDL/LDL-c ratio, are related to a functional measure of atherosclerosis.
      Therefore correction of oxLDL for LDL particle number may improve the clinical
      usefulness of oxLDL measurement.

PMID- 18802197
TI  - Perinatal n-3 fatty acid deficiency selectively reduces myo-inositol levels in
      the adult rat PFC: an in vivo (1)H-MRS study.
AB  - To investigate the effects of omega-3 fatty acid deficiency on
      phosphatidylinositol signaling in brain, myo-inositol (mI) concentrations were
      determined in the prefrontal cortex (PFC) of omega-3 fatty acid deficient rats by
      in vivo proton magnetic resonance spectroscopy ((1)H-MRS). To generate graded
      deficits in PFC docosahexaenoic acid (22:6n-3) (DHA) composition, perinatal and
      postweaning alpha-linolenic acid (18:3n-3) (ALA) deficiency models were used.
      Adult male rats were scanned in a 7T Bruker Biospec system and a (1)H-MRS
      spectrum acquired from the bilateral medial PFC. Rats were then challenged with
      SKF83959, a selective agonist at phosphoinositide (PI)-coupled dopamine D(1)
      receptors. Postmortem PFC fatty acid composition was determined by gas
      chromatography. Relative to controls, PFC DHA composition was significantly
      reduced in adult postweaning (-27%) and perinatal (-65%) ALA-deficiency groups.
      Basal PFC mI concentrations were significantly reduced in the perinatal
      deficiency group (-21%, P = 0.001), but not in the postweaning deficiency group (
      1%, P = 0.86). Among all rats, DHA composition was positively correlated with mI
      concentrations and the mI/creatine (Cr) ratio. SKF83959 challenge significantly
      increased mI concentrations only in the perinatal deficiency group (+16%, P =
      0.02). These data demonstrate that perinatal deficits in cortical DHA accrual
      significantly and selectively reduce mI concentrations and augment receptor
      generated mI synthesis.

PMID- 18802198
TI  - Erectile dysfunction management for the future.
AB  - The field of erectile dysfunction (ED) management over time has witnessed
      assorted interventions to enable men to perform sexual intercourse. In recent
      times, major progress in ED research has led to increasingly effective treatments
      based on a refined knowledge of the scientific basis for penile erection. Current
      concepts suggest that therapeutic prospects on the horizon include novel
      pharmacotherapies, growth factor therapy, gene therapy, and regenerative
      medicine. The purpose of this review is to present the foundations for future
      therapies in ED management.

PMID- 18802199
TI  - Androgens play a pivotal role in maintaining penile tissue architecture and
      erection: a review.
AB  - Androgens are essential for development, growth, and maintenance of penile
      structure, and regulate erectile physiology by multiple mechanisms. Here we
      provide a concise overview of the basic research findings pertaining to androgen
      modulation of erectile tissue architecture and physiology. A significant body of
      evidence exists pointing to a critical role of androgens in erectile physiology.
      Studies in animal models have provided fundamental knowledge on the role of
      androgens in modulating tissue architecture and cellular, molecular, and
      physiological mechanisms. Based on data from our laboratory and those reported by
      others, we believe that androgens play a pivotal role in maintaining the
      structure and function of the peripheral penile nerve network, the structural
      integrity of the corpora cavernosa, the tunica albuginea, and the endothelium of
      the cavernous spaces. Further, androgens play an important role in regulating the
      differentiation of precursor cells into trabecular smooth muscle. In this review,
      we will focus our discussion on findings pertaining to the role of androgens in
      regulating penile tissue architectural elements in modulating penile function.
      This knowledge has a profound impact on the potential use of androgens in the
      clinical setting to treat patients with erectile dysfunction.

PMID- 18802201
TI  - Reducing stroke in-hospital mortality: organized care is a complex intervention.

PMID- 18802200
TI  - Adjudin targeting rabbit germ cell adhesion as a male contraceptive: a
      pharmacokinetics study.
AB  - Adjudin (1-(2,4-dichlorobenzyl)-1H-indazole-3-carbohydrazide; formerly called AF
      2364) has been shown to inhibit spermatogenesis by disrupting anchoring junctions
      at the Sertoligerm cell interface. This, in turn, leads to germ cell loss from
      the seminiferous epithelium, and transient infertility. Adjudin's efficacyin
      inhibiting spermatogenesis, the recovery of spermatogenesis after cessation of
      the drug, and side effects were examined in adult male Japanese rabbits. The
      pharmacokinetics profiles of adjudin in rabbits after oral administration and
      after intravenous injection were compared. Rabbits received 25 mg/kg adjudin once
      weekly for 4 consecutive weeks either by intravenous injection or by gavage.
      Vehicle-treated rabbits were used as controls. At 1, 2, 3, 4, and 8 weeks after
      treatment, testes were removed for microscopic examination to assess the status
      of spermatogenesis. Four weeks after intravenous cessation of adjudin, the
      recovery of spermatogenesis also was monitored. Blood was withdrawn after first
      administration to measure plasma concentrations of adjudin by high-performance
      liquid chromatography. Four weeks after intravenous treatment, examination of
      testis sections showed rapid exfoliation of elongated/elongating spermatids and
      the presence of large multinucleated cells; more than 95% of germ cells were
      absent from the seminiferous epithelium. Intravenous treatment showed a more
      severe disturbance of spermatogenesis compared with gavage treatment, which was
      correlated with bioavailability of the drug. The areas under the curve for
      intravenous injection and gavage were 20.11 +/- 1.90 and 2.23 +/- 0.45 mg x h x
      L(-1), respectively. These results illustrate the potential of adjudin as a male
      contraceptive, and the efficacy is associated with the bioavailability of the
      drug.

PMID- 18802202
TI  - Therapeutic potential and possible risks of pleiotropic growth factors in
      ischemic stroke.

PMID- 18802203
TI  - Interplay of vascular phenotype and metabolic phenotype in populations with or
      without type 2 diabetes.

PMID- 18802204
TI  - Neuroglobin: endogenous neuroprotectant or maintenance of homeostasis?

PMID- 18802205
TI  - Metabolic syndrome and stroke.

PMID- 18802206
TI  - Delay to diagnosis in acute pediatric arterial ischemic stroke.
AB  - BACKGROUND AND PURPOSE: For the clinician, the diagnosis of arterial ischemic
      stroke (AIS) in children is a challenge. Prompt diagnosis of pediatric AIS within
      6 hours enables stroke-specific thrombolytic and neuroprotective strategies.
      METHODS: We conducted a retrospective study of prospectively enrolled consecutive
      cohort of children with AIS, admitted to The Hospital for Sick Children, Toronto,
      from January 1992 to December 2004. The data on clinical presentation, symptom
      onset, emergency department arrival, neuroimaging and stroke diagnosis were
      recorded. The putative predictors of delayed diagnosis were selected a priori for
      analysis. RESULTS: A total of 209 children with AIS were studied. The median
      interval from symptom onset to AIS diagnosis was 22.7 hours (interquartile range:
      7.1 to 57.7 hours), prehospital delay (symptom onset to hospital arrival) was 1.7
      hours (interquartile range: 49 minutes to 8.1 hours), and the in-hospital delay
      (presentation to diagnosis) was 12.7 hours (interquartile range: 4.5 to 33.5
      hours). The initial assessment was completed in 16 minutes and initial
      neuroimaging in 8.8 hours. The diagnosis of AIS was suspected on initial
      assessment in 79 (38%) children and the initial neuroimaging diagnosed AIS in
      47%. The parent's help seeking action, nonabrupt onset of symptoms, altered
      consciousness, milder stroke severity, posterior circulation infarction and lack
      of initial neuroimaging at a tertiary hospital were predictive delayed AIS
      diagnosis. CONCLUSIONS: In the diagnosis of AIS, significant prehospital and in
      hospital delays exist in children. Several predictors of the delayed AIS
      diagnosis were identified in the present study. Efforts to target these
      predictors can reduce diagnostic delays and optimize the management of AIS in
      children.

PMID- 18802207
TI  - Induction of neurogenesis in the adult dentate gyrus by cortical spreading
      depression.
AB  - BACKGROUND AND PURPOSE: Spreading depression (SD) is an epiphenomenon of
      neurological disorders, like stroke or traumatic brain injury. These diseases
      have been associated with an increased neurogenesis in the adult rodent dentate
      gyrus. Such proliferative activity can also be induced by conditions that--like
      SD--coincide with a disturbed neuronal excitability, eg, epilepsy. Thus we
      hypothesized that SD might likewise influence hippocampal neurogenesis and
      potentially act as mediator of injury-induced neurogenesis. METHODS: Repetitive
      cortical SD were induced by epidural application of 3 mol/L KCl. At different
      time points thereafter dentate gyrus neurogenesis was investigated by means of
      intraperitoneal bromodeoxyuridine injections and immunocytochemistry. Spatial
      learning and memory was tested in a Morris water maze. RESULTS: Cortical SD
      significantly increased proliferative activity in the ipsilateral subgranular
      zone on days 2 and 4. We detected about 280% more newborn cells in the dentate
      gyrus of rats that received bromodeoxyuridine during the first week after SD and
      were allowed to recover for 6 weeks. Most of these cells expressed the mature
      neuronal marker NeuN. The mitogenic action of SD was suppressed by systemic
      administration of the NMDA receptor antagonist MK-801. Behavioral performance of
      SD animals in the Morris water maze did not improve significantly. CONCLUSIONS:
      From our data we postulate that the increased dentate gyrus neurogenesis observed
      after brain injury may at least partly be mediated by SD-like epiphenomena.
      Furthermore they indicate that even a strongly enhanced dentate gyrus
      neurogenesis may occur without significant improvements in hippocampus-dependent
      spatial learning and memory.

PMID- 18802208
TI  - Retrograde catheterization of haemodialysis fistulae and grafts: angiographic
      depiction of the entire vascular access tree and stenosis treatment.
AB  - BACKGROUND: The European Best Practice Guidelines on Vascular Access propose
      magnetic resonance angiography (MRA) of dysfunctional dialysis fistulae and
      grafts if visualization of the complete arterial inflow and outflow vessels is
      needed. In a prospective multi-centre study we determined the technical success
      rate of complete vascular access tree depiction by digital subtraction
      angiography (DSA) as an alternative to MRA. Instead of a more invasive brachial
      artery of femoral artery approach, we performed a retrograde catheterization of
      the venous outflow or graft, and stenoses were treated in connection with DSA.
      METHODS: A catheter was advanced into the central arterial inflow after
      retrograde puncture of the venous outflow or graft for depiction of the complete
      inflow, access region and complete outflow. Access DSA through femoral artery
      puncture was done if the retrograde approach failed to depict the complete
      vascular access tree. Stenoses with a luminal diameter reduction >or=50% were
      treated, if possible, in connection with DSA. RESULTS: A total of 116
      dysfunctional haemodialysis fistulae and 50 grafts were included. Retrograde DSA
      depicted the complete vascular tree in 162 patients (97.6%). The arteriovenous
      anastomosis of four fistulae could not be negotiated by a catheter. DSA
      demonstrated 247 significant stenoses: 30, 128 and 89 were located in the
      arterial inflow (12.1%), AV anastomosis and graft region (51.8%) and venous
      outflow (36.0%), respectively. Ten patients (6.0%) had no stenosis. Eight (4.8%),
      55 (33.1%) and 33 (19.9%) patients demonstrated stenoses in only inflow, access
      region or outflow, respectively. Stenoses in two or three vascular territories
      were present in 53 (31.9%) and 7 (4.2%) patients, respectively. A technically
      successful endovascular intervention was obtained in 135 of the 139 patients
      (97.1%) who underwent angioplasty and/or stent placement. Additional sheath
      insertion by antegrade outflow puncture was needed in 46 patients (33.1%) for the
      treatment of coexisting venous outflow stenoses, located downstream from the
      retrograde positioned sheath. Two minor complications were observed at
      DSA/angioplasty. CONCLUSION: As an alternative to MRA, full retrograde DSA is
      safe and effective for stenosis detection and stenosis treatment. However, access
      evaluation by a non-invasive imaging modality such as colour duplex ultrasound
      will be sufficient in most cases as proximal inflow stenoses are encountered in a
      minority of patients. Full retrograde DSA, including complete arterial inflow
      depiction, may then be reserved for cases with an unsuccessful outcome following
      endovascular intervention of stenoses depicted at ultrasound.

PMID- 18802209
TI  - Biosimilars and biopharmaceuticals: what the nephrologists need to know--a
      position paper by the ERA-EDTA Council.

PMID- 18802210
TI  - Obesity, diabetes, adiponectin and the kidney: a podocyte affair.

PMID- 18802212
TI  - The taming of the shrew: batterers' constructions of their wives' narratives.
AB  - Constructing a life story is a need shared by all humans to give their lives
      meaning and coherence. This article explores some of the narrative devices that
      batterers use to achieve a sense of coherence when telling their stories and
      justifying their violent behavior. A central theme that emerged from these
      stories centered on the men's perception of their wives as the embodiment of
      their own emotions and inner world. Two narrative strategies were identified in
      this context: (a) The construction of a "couple narrative" that focused on an
      idealized marital relationship rather than "allowing" the wife her story and (b)
      constructing a story around the theme of "she's not the same woman I married,"
      which portrays the wife as "a shrew" and the violence as an attempt to discipline
      her. The stories of 18 batterers were used for this analysis, and two narratives
      were used to illustrate these strategies.

PMID- 18802213
TI  - Domestic violence and contraceptive use in a rural Indian village.
AB  - This study uses qualitative methods to examine how domestic violence affects the
      use of contraceptives by women in a rural village in India. The study highlights
      how multilevel factors are linked to a woman's ability to contracept and make
      fertility decisions in a context where being a wife implies obedience, limited
      mobility, sexual availability, and high fertility. The authors find that violence
      is normalized, or considered acceptable, if women do not adhere to expected
      gender roles. Although women's ability to make autonomous decisions is shown to
      be limited, the study explores covert strategies used to avoid pregnancy, which
      also tend to increase women's risk of experiencing domestic violence.

PMID- 18802214
TI  - To Endure: (for Michelle Gardner-Quinn).

PMID- 18802215
TI  - Control of development of gastrointestinal system in neonates.
AB  - Our recent studies of structure and function of gastrointestinal tract mucosa
      revealed that the domestification of Sus scrofa corresponds with the significant
      slowing of the organ development. On top of genetic potential, the nutritional
      factors (or more precisely - lack of certain biologically active substances in
      the feed of pregnant sows) are responsible. Moreover, feeding neonates with milk
      replacers instead of mother's milk further slows down the development. This is
      manifested by reduced mitotic activity in the crypts and enhanced apoptosis of
      enterocytes. The negative effects consist of slower replacement of fetal type,
      vacuolated enterocytes to adult type enterocytes, modified profile of brush
      border enzymes, alterations in intestinal mucosa barrier, higher susceptibility
      to infectious agents, and many others. On the other hand, farmers in order to
      intensify the production, shorten the suckling period imposing the neonatal
      piglets to be weaned at 3-4 weeks of life and even earlier. Altogether, it makes
      the weaning disorders one of the most important problems in pig husbandry, and
      the mortality of piglets in the leading pig-producing countries still reaches
      10%. A number of strategies have been developed to counteract the post-weaning
      problems. One of them is to stimulate the development of the gastrointestinal
      tract of the neonate by supplementation of the sow diet with certain biologically
      active substances and plants. The other idea is to speed up the postnatal
      development of the gut mucosa for example by plant lectins. Lessons from pig
      studies can be also useful in human nutrition and medicine since the development
      of porcine gastrointestinal tract shows a great similarity to that of humans.

PMID- 18802216
TI  - Role of leptin during perinatal metabolic programming and obesity.
AB  - The incidence of obesity is rapidly increasing all over the world in epidemic
      proportions.The epidemia now affects young children and accumulative evidences
      suggest that the origin of the disease may occur during foetal development and
      early life. This has introduced the concept of "developmental programming"
      supported by experimental studies in animal models and numerous epidemiological
      data. This concept supports the idea that nutritional and hormonal status during
      pregnancy and early life could interfere irreversibly on the development of the
      organs involved in the control of food intake and metabolism and particularly the
      hypothalamic structures responsible of the establishment of the ingestive
      behaviour and regulation of energy expenditure. The mechanisms responsible of
      this developmental programming remain poorly documented. However, recent research
      indicate that the adipokine leptin plays a critical role in this programming.

PMID- 18802217
TI  - A postgenomic integrated view of prostaglandins in reproduction: implications for
      other body systems.
AB  - Prostaglandins are primary mediators of pain and are involved in pathological
      conditions such as hypertension, cancer and inflammation but are also needed for
      normal function of the female reproductive system. This may hold true for other
      systems because long term use of selective COX-2 inhibitors such as VIOXX and
      BEXTRA was associated with heart failure, leading to their withdrawal. A thorough
      study of the contribution of prostaglandins in the regulation of normal body
      function is clearly needed. A major drawback of the current therapeutic
      strategies aiming at controlling PGs is that they aim at early steps of
      biosynthesis thus blocking all PGs, good and bad. However, PGs often work as
      opposing dyads such as PGI2-TXA2 in the vascular system and PGF2alpha-PGE2 in the
      female reproductive system. The paradigm thus appears as effecting selective
      synthesis, transport and action of individual PG isoforms. In this respect, the
      female reproductive system appears as an ideal study model. Data from human and
      animal genome projects allowed identifying the corresponding members of the
      biosynthetic and signal transduction components of the PG system in different
      animal species. Of particular interest was that PG terminal synthase shared
      similarities or identity with enzymes previously known for steroid or sugar
      metabolism and free radical detoxification. We present here an integrated view of
      PG action based on observations in the female reproductive system, but with
      potential strategic implications for cardiovascular and metabolic complications.

PMID- 18802218
TI  - Biological effects of 2-oxoglutarate with particular emphasis on the regulation
      of protein, mineral and lipid absorption/metabolism, muscle performance, kidney
      function, bone formation and cancerogenesis, all viewed from a healthy ageing
      perspective state of the art--review article.
AB  - The fact that men and women are living longer than they have ever done before is
      something in which we can all rejoice. However, the process of ageing is
      associated with changes in skeletal, muscular, gastrointestinal, neural hormonal
      and metabolic processes that seriously affect an individual's performance and
      quality of life. Indeed, such changes can be contributory to a loss of
      independence in the elderly. This state-of-the art address highlights the main
      changes found to occur with ageing whilst simultaneously reporting findings of in
      vivo and in vitro studies designed to elucidate the potential of the Krebs cycle
      intermediate - alpha-ketoglutaric acid (AKG) in protecting elderly body systems
      from failing and degradation. The topics of paramount importance include impaired
      bone structure and strength, amino acid and mineral absorption, muscle
      performance, as well as highlighting the role of Krebs cycle intermediates in the
      debilitating changes that occur with end-stage renal failure and the regulation
      of the lipid metabolism. Finally, focus will be given to the role of 2
      oxoglutarate as a potent protective factor in connection with the development of
      malignant cells in the body.

PMID- 18802219
TI  - Physiology and pathophysiology of liver inflammation, damage and repair.
AB  - The liver is the largest organ of the body. It is located between the portal and
      the general circulation, between the organs of the gastrointestinal tract and the
      heart. The main function of the liver is to take up nutrients, to store them, and
      to provide nutrients to the other organs. At the same time has the liver to take
      up potentially damaging substances like bacterial products or drugs delivered by
      the portal blood or microorganisms, which reach the circulation. The liver is not
      only an important power and sewage treatment plant of the body. In fact, the
      liver is probably the best example for a cheap recycling system. Both parenchymal
      and nonparenchymal liver cells participate in the clearance activities. The
      function of the liver as clearance organ, however, harbors the danger that the
      substances that should be degraded and/or eliminated lead to tissue damage. Thus,
      effective defense mechanisms are necessary. Among the nonparenchymal cells
      Kupffer cells, sinusoidal endothelial cells, and natural killer (NK) lymphocytes
      exert cellular defense functions for the whole body but also for the liver
      itself. Furthermore, each cell type of the liver, including the hepatocytes,
      possesses its own defense apparatus.

PMID- 18802220
TI  - Static versus dynamic training programs for muscular strength using the knee
      extensors in healthy young - men.
AB  - Nineteen young and healthy males (18-21 years) were subjected to two strength
      training programs (dynamic and static) by using each of the knee extensor
      (quadriceps) muscles in each subject for each program. The duration of the study
      was 10 weeks with a frequency of three sessions per week. Pre-training and
      posttraining strength measurements were made for each program. Weekly post
      training measurements were also made. The difference between the pre- and post
      training mean strength measurements for the two programs and the difference
      between the mean strength increases in the two programs were all found to be
      statistically significant (p c 0.05). This showed that muscular strength could be
      increased by either of the training programs. However, more positive effects
      seemed to have been achieved through the isometric or static strength training
      program of strength gains. J Orthop Sports Phys Ther 1986;8(5):243-247.

PMID- 18802221
TI  - Evaluation of knee extensor mechanism disorders: clinical presentation of 1 12
      patients*.
AB  - Results of physical therapy evaluation of 112 patients with extensor mechanism
      disorders (chondromalacia patella, infrapatellar tendinitis, and peripatellar
      pain) are presented. An equal number of male and female patients were evaluated
      and of the 73 patients with unilateral involvement (65%) there were equal numbers
      of right and left involved knees. Running was the activity most commonly
      associated with pain, followed by basketball and tennis. Stairclimbing was
      painful in 79% of the patients, with ascending being more painful than descending
      in patients reporting a clear-cut difference. Hamstring and quadriceps tightness
      was statistically significant relative to the uninvolved limb although
      clinically, negligible differences were measured. The inferior pole of the
      patella was the most tender site to palpation, followed by medial peripatellar
      structures, then lateral sites. Biomechanical malalignment was not detected by
      the attending therapist in the majority of patients. The authors emphasize
      careful assessment of flexibility, quadriceps (VMOIVL) imbalance, and
      biomechanical alignment in performing a thorough evaluation of patients with
      extensor mechanism disorders. J Orthop Sports Phys Ther 1986;8(5):248-254.

PMID- 18802222
TI  - Physical therapy treatment of knee extensor mechanism disorders: comparison of
      four treatment modalities*.
AB  - Fifty-three patients diagnosed as having one of several types of extensor
      mechanism disorders of the knee were randomly assigned to one of four treatment
      groups to assess the effects of one of four different modalities (ice,
      phonophoresis, iontophoresis, and ultrasound/ice contrast). Following four
      physical therapy treatments over a 10-day period, the group treated with the
      ultrasound/ice contrast demonstrated the greatest subjective improvement (47%).
      The pre- to post-treatment isometric strength resulted in a 28% improvement in
      knee extension strength and a 34% improvement in knee flexion strength. The
      authors emphasize that evaluation should include assessment of quadriceps tone
      and strength as well as careful palpation to determine the irritable structures.
      Ultrasound/ice is advocated as the most effective choice of the modalities tested
      for treatment of pain associated with extensor mechanism disorders. J Orthop
      Sports Phys Ther 1986;8(5):255-259.

PMID- 18802223
TI  - Postural correction in persons with neck pain (I. A survey of neck positions
      recommended by physical therapists).
AB  - The primary purpose of this exploratory study was to determine if two corrective
      neck postures, axial extension and neutral neck position, are widely used by
      physical therapists to relieve neck pain and spasm of the upper trapezius. A
      random sample of physical therapists in New York, New Jersey, and Puerto Rico
      were polled by means of a structured questionnaire. Of the 52 respondents, 32
      reported that patients with neck pain and spasm of the upper trapezius often
      assume a forward head position (p < 0.001). A similar number (N = 33) reported
      that they often used postural training in their treatment of neck pain and spasm
      of the upper trapezius (p < 0.001). Even though there is no scientific basis for
      recommending either of the two corrective postures, the study revealed two groups
      of physical therapists, those who recommend axial extension (N = 21) and those
      who advocate neutral neck position (N = 25). J Orthop Sports Phys Ther
      1986;8(5):235-239.

PMID- 18802224
TI  - Postural Correction in Persons with Neck Pain (II. Integrated Electromyography of
      the Upper Trapezius in Three Simulated Neck Positions).
AB  - In the previous paper (Enwemeka, Bonet, Ingle, et al. 8:235-239, 1986) we showed
      that patients with neck pain and spasm of the upper trapezius often assume a
      forward head position, and that two neck positions, axial extension, and neutral
      neck position are frequently used by physical therapists to correct this faulty
      neck posture. Because there is no scientific basis for recommending either of the
      two corrective neck positions, we simulated the three neck positions in 10 normal
      adults and compared the integrated electromyography (IEMG) of the upper trapezius
      to determine if the muscle shows less activity in any of the two corrective
      positions. The results showed significantly less IEMG of the upper trapezius in
      each of the two corrective neck positions than in the faulty neck position (p <
      0.001). No statistically significant difference was found between the IEMGs
      recorded in the two corrective neck positions (p > 0.10). The implications and
      limitations of these findings are discussed along with suggestions for future
      studies. J Orthop Sports Phys Ther 1986;8(5):240-242.

PMID- 18802225
TI  - The Effect of Electrical Stimulation and lsokinetic Exercise on Muscular Power of
      the Quadriceps Femoris.
AB  - The purpose of this study was to compare the power and strength changes, of the
      quadriceps femoris muscle group, following 6 weeks of training. Twenty-seven
      moderately trained, female subjects were placed into three equated groups:
      electrical stimulation plus isokinetic exercise (ES + IE), isokinetic exercise
      (IE), and electrical stimulation (ES). A CybexQ I1 isokinetic dynamometer was
      used for testing the quadriceps ' power and strength output at the velocities of
      0, 30, 100, and 180 O/ sec. The ES + IE and ES groups received faradic
      stimulation (progressive from 10- 20 mA) from a Multitone Multifaradic Unit
      (model F283, Multitone Electric Co., London, England). In addition, the ES + IE
      group performed isokinetic contractions concurrently with the faradic
      stimulation. Thigh circumference (TC) and time to peak tension (TPT) were also
      calculated during the pre-, mid-, and post-tests. Results indicated that a
      significant power increment was evident between the pre- and posttests and the
      pre- and mid-tests for the combined groups (p < 0.05). However, there were no
      significant power increases between the three separate groups at the four
      velocities. Significant power differences (P c 0.05) for the combined groups
      between the pre- and post-tests and the pre- and mid-tests at the isokinetic
      velocities of 30 and OO/sec were also identified. TPT and TC did not change
      significantly for any group over the 6-week training period. This study indicated
      that the combined effects of ES + IE, IE, and ES are potentially effective means
      of improving power and strength; however, data did not reveal one method of
      training as being significantly superior to another. J Orthop Sports Phys Ther
      1986;8(5):260-268.

PMID- 18802226
TI  - Validity and reliability of leg length measurements.
AB  - This study was conducted to examine the validity and reliability of the leg
      length measurements with a tape measure. The purpose of this study was to
      determine: 1) the validity of the leg length measurements through comparison with
      x-rays, and 2) the intertester reliability. Thirty healthy subjects between the
      ages of 18 and 65 were studied. Each subject was positioned supine on an x-ray
      table. A radiopaque ruler marked in 1 mm increments was placed on the table. Two
      physical therapists measured the right leg length of each subject from anterior
      superior iliac supine to medial malleolus with a pliable metal tape measure. X
      rays were taken by the slit scanography method. Pearson product-moment and
      intraclass correlation coefficients (r and ICC, respectively) were used to
      analyze the data. The value of r for the comparison: 1) between therapists was
      0.98, 2) between therapist 1 and x-ray measure was 0.98, and 3) between therapist
      2 and x-ray measure was 0.98. The value of ICC for the comparison: 1) between
      therapists was 0.99, 2) between therapist 1 and x-ray measure was 0.99, and 3)
      between therapist 2 and x-ray measure was 0.99. The findings of this study
      indicate that the leg length measurements from anterior superior iliac spine to
      the medial malleolus with tape measure are valid and reliable. Hence, confidence
      can be placed in the accuracy of clinical measures. J Orthop Sports Phys Ther
      1986;8(4):185-188.

PMID- 18802227
TI  - Reliability of a noninvasive method for measuring the lumbar curve*.
AB  - The purposes of this paper were to describe a clinically useful and noninvasive
      method of characterizing the shape of the lumbar spine and to evaluate the
      reliability and validity of this measurement technique. A flexible ruler was
      applied to the skin over the lumbar spines of 23 normal adults and an angle in
      degrees between two spinous processes (L 1 -S2) was calculated. lntratester test
      retest reliability was good (ICC = 0.97, N = 89) for two separate measures of two
      spinal postures. The validity of the flexible ruler measurements was also good
      when compared to two different measurement techniques from a limited number of
      patient roentgenographs. The flexible ruler was determined to be a reliable and
      valid measurement technique for the shape of the lumbar spine and may prove
      helpful in quantifying lumbar postures and the effectiveness of clinical
      treatments designed to affect lumbar postures. J Orthop Sports Phys Ther
      1986;8(4):180-184.

PMID- 18802228
TI  - Electrical muscle stimulation and isometric exercise effects on selected
      quadriceps parameters*.
AB  - The purpose of the study was to compare the effects of 1) monopolar (MI) and
      bipolar (BI) electrical muscle stimulation (EMS) concurrent with isometric
      exercise, and 2) EMS (MI and BI) concurrent with isometric exercise to isometric
      exercise (I) alone on girth, dynamic strength, muscular power, and muscular
      endurance of the right quadriceps muscle. All three experimental groups completed
      a 6-week program of training on the right lower limb which was isometrically
      restrained at -30 degrees knee extension. Additionally, the MI and BI groups
      received low frequency (65 Hz) EMS. A control group (C) was involved in pre- and
      post-testing sessions only. Results indicated that 1) EMS concurrent with
      isometric exercise was more effective in improving quadriceps strength over a
      group that did no training, but was no more effective than isometric exercise
      alone; 2) the two EMS techniques yielded similar results for healthy innervated
      muscle; 3) dynamic strength was minimally increased by EMS; 4) power was
      positively increased more by the monopolar technique; and 5) endurance was
      positively increased more by the bipolar technique. It was concluded that while
      the two techniques of EMS concurrent with isometric exercise have the potential
      to positively increase selected physiological parameters in healthy innervated
      muscle, the greatest benefits will be noted for the weaker muscle. J Orthop
      Sports Phys Ther 1986;8(4):203-209.

PMID- 18802229
TI  - Case study: rehabilitation of multiple joint instability associated with ehlers-
      danlos syndrome.
AB  - Ehlers-Danlos syndrome (EDS) is a familiar disorder of the connective tissues
      which often results in orthopaedic complications, the most significant being
      multiple joint instabilities. This article reviews EDS and presents a case in
      which multiple joint instability in a 10-year-old female with EDS type Illltype
      XI was successfully controlled with an intensive therapeutic exercise program. J
      Orthop Sports Phys Ther 1986;8(4):193-198.

PMID- 18802230
TI  - Optimal application of the N-k table as an exercise device for knee extension*.
AB  - The purpose of this study was to determine the optimal position of the N-K table*
      resistance arm relative to the exercise arm which might best match the
      biomechanics of the knee extensor musculature and serve to improve the use of the
      N-K table in rehabilitation of the injured or painful knee. First, torque
      position relationships were derived for the knee extensors of six subjects using
      a computer controlled dynamometer (KinlCom). section sign Next, relative torque
      position relationships were established for four different N-K table resistance
      arm offsets using the dynamometer (KinlCom) as a robotic device to push the
      exercise arm of the N-K table through the range of motion while recording the
      torque. Different torque position relationships were recorded when the offset was
      10, 55, 80, or 100 O from the exercise arm. The 55 O offset appeared optimal for
      most knee extension exercises. However, other resistance arm offsets tested could
      be useful in rehabilitation of specific knee problems. J Orthop Sports Phys Ther
      1986;8(4):189-192.

PMID- 18802231
TI  - Aerobic Capacity after Contracting lnfectious Mononucleosis.
AB  - Infectious mononucleosis can be disabling to athletes of all ages. Traditionally,
      long periods of limited physical activity are prescribed. During this time period
      a significant level of detraining can occur. Sixteen cadets from USMA who were
      identified as having mononucleosis had their aerobic capacity determined
      immediately after becoming afebrile. Nine of these cadets then entered a 2-week
      exercise program while the others remained inactive. After this time period all
      cadets were allowed to exercise at their own discretion. After an additional 2
      week period (4 weeks after becoming afebrile), aerobic capacity was again
      determined. There were no differences within the groups when comparing VO2 max,
      METS, or run time to exhaustion on the two aerobic tests. One individual served
      as a case study with aerobic tests every week for 4 weeks and then 6 months after
      becoming afebrile. Again, no differences were observed in any variables measured.
      Thus, prolonged bed rest does not seem to be indicated for the individual
      recovering from mononucleosis. Noncontact activities can be initiated as soon as
      the fever disappears. J Orthop Sports Phys Ther 1986;8(4):199-202.

PMID- 18802232
TI  - "Tennis Elbow": A Manual Therapist's Perspective.
AB  - Ever since the turn of this century the pathogenetic mechanism of "tennis elbow"
      has been a controversial issue. The following article briefly describes the
      varying opinions and then proposes a working hypothesis to explain the
      unpredictable presentation of lateral forearm pain. The articular mechanics of
      the elbow joint are described in detail followed by a discussion of intrinsic and
      extrinsic factors pertinent to tennis elbow. The intent is to logically present a
      multifactorial syndrome, such as tennis elbow, from the perspective of manual
      therapy which incorporates a global evaluation of the clinical picture. J Orthop
      Sports Phys Ther 1986;8(3):134-142.

PMID- 18802233
TI  - Upper extremity strength and strength relationships among young women.
AB  - The static strength of 10 upper extremity muscle groups of 3 1 young women was
      tested bilaterally to gain a preliminary estimate of the strength of the muscle
      groups and the relationship between the strength of the muscle groups. Strength
      was measured using a hand-held dynamometer. Descriptive statistics were
      calculated for the measurements obtained. Inferential statistics revealed a
      significant difference in strength between the left and right side for only three
      muscle groups. The only antagonistic muscle groups that differed significantly on
      both the left and right side were the elbow flexor and extensor muscles. The
      strength of each muscle group was significantly related to the strength of every
      other muscle group on each side. The strength values and strength relationships
      reported herein should prove useful to clinicians testing the upper extremity
      strength of young women. J Orthop Sports Phys Ther 1986;8(3):128-133.

PMID- 18802235
TI  - Suggestions from the clinic ankle injuries: clinical observations.
AB  - This article presents a simple rationale protocol to improve the function of
      ankle injuries. This approach allows a step by step progression in exercise that
      can be carried out as a home program. J Orthop Sports Phys Ther 1986;8(3):153
      156.

PMID- 18802234
TI  - The anterior cruciate ligament: a review of recent concepts.
AB  - The anterior cruciate ligament (ACL) consists of a small anteromedial band and a
      larger posterolateral band. Recent findings have shown the ACL to play a major
      role in the function of the knee joint. The ACL prevents anterior luxation of the
      tibia, limits tibial rotation, and resists valgus and varus stress to the knee.
      The most common mechanism of ACL injury involves hyperextension of the knee with
      a rotational component. Diagnosis of an ACL lesion consists of an accurate
      history, clinical tests and often, arthroscopic investigation. Treatment of an
      ACL injury may consist solely of a rehabilitation program, may involve surgical
      intervention, or a combination of the two. Many surgical procedures both intra
      articular and extra-articular, have been used in the past. The most successful
      approach at this time appears to be a combination of intra-articular and extra
      articular procedures. A contemporary trend in rehabilitation following surgery is
      the use of graduated stages of treatment beginning immediately postsurgery and
      continuing through to full return to activity. J Orthop Sports Phys Ther
      1986;8(3):110-122.

PMID- 18802236
TI  - Effect of a tightened anterior band of the ulnar collateral ligament on
      arthrokinematic motion at the humeroulnar joint.
AB  - This study examined the effect of the anterior band of the ulnar collateral
      ligament on arthrokinematic motion of the elbow joint. Five cadaver upper
      extremities were used in the investigation. With the humerus stabilized in a
      specially designed clamp, normal elbow joint motion was determined through
      markings made on the trochlea at six points within the range of movement. A l/ls
      inch drill hole was used to make the markings on each trochlea, and a red latex
      dye was injected into these markings to indicate the track of motion. The
      anterior band of the ulnar collateral ligament in each of the specimens was then
      shortened and tied. The articular surface of each trochlea was again marked as
      before, but with a green latex dye. Upon disarticulation, each trochlea exhibited
      six marker holes, each %6 inch in diameter. Each of the marker holes contained
      both red and green latex dyes. It was concluded that tightening of the anterior
      band of the ulnar collateral ligament resulted in no observable change in
      arthrokinematic motion of the elbow joints examined. J Orthop Sports Phys Ther
      1986;8(3):123-127.

PMID- 18802237
TI  - The effect of electrical stimulation on quadriceps strength and thigh
      circumference in menisectomy patients.
AB  - The purpose of this study was to assess the effects of two training regimens:
      electrical stimulation and exercise versus exercise alone in increasing
      quadriceps strength and thigh circumference. Subjects were 21 postmenisectomy
      patients who were randomly assigned to one of the two groups. The experimental
      group received quadriceps stimulation 5 days/week for 3 weeks. Both groups
      maintained a knee rehabilitation program consisting of quadriceps and hamstrings
      isometric and isotonic strengthening exercises 3 days/week. Results indicated
      that electrical stimulation combined with a regular program of quadriceps
      exercise have a significant effect in strengthening the quadriceps at four
      different contraction speeds (1 20, 180, 240, and 300 degrees /sec). The control
      group exhibited significant strength gains only at the slower two speeds. Thus,
      electrical stimulation may be valuable in strengthening at high speeds of
      contraction. The thigh circumference changes were significant for both groups. J
      Orthop Sports Phys Ther 1986;8(3):143-146.

PMID- 18802238
TI  - Evaluation of ankle joint proprioception following injection of the anterior
      talofibular ligament*.
AB  - The purpose of this investigation was to measure ankle joint proprioception
      preceding and following injection of Xylocaine into the anterior talofibular
      ligament (ATFL). Previous investigators have indicated that the typical inversion
      ankle sprain causes decreased afferent input from the joint which results in a
      proprioceptive deficit at the ankle. It was hypothesized that anesthesia of the
      ATFL would simulate this proprioceptive deficit. Fourteen individuals were
      blindfolded and subjected to pre-test proprioceptive measurements on a multiaxial
      balance evaluator. Xylocaine was introduced into the ATFL and post-test
      measurements were taken. A significant increase in average time in balance was
      found following anesthesia of the ATFL. The unexpected results may indicate that
      multiple trials caused a learning effect. This supports the contention of other
      investigators that proprioceptive deficits can be improved with training. It is
      concluded that proprioceptive training should be included in the overall
      rehabilitation program following ankle sprains. J Orthop Sports Phys Ther
      1986;8(2):70-76.

PMID- 18802239
TI  - Comparison of four treatment approaches for lateral epicondylitis of the elbow*.
AB  - The relative effectiveness of four treatment protocols on lateral epicondylitis
      of the elbow were compared by assessing patient pain responses with a modified
      McGill Pain Questionnaire. The four protocols examined were ultrasound and a home
      program, ultrasound with 10% hydrocortisone and a home program, transcutaneous
      electrical nerve stimulation and a home program, and subcutaneous injection with
      a steroid and a home program. A total of 48 subjects were used in the study, with
      12 in each treatment category. All protocols descriptively showed a decrease in
      mean pain intensity after the 5-day treatment time, and all of the pain indexes
      showed some statistical differences between pre- and post-treatment values,
      indicating that all the treatments were effective in reducing pain. The analysis
      also demonstrated, however, that the four treatment protocols did not differ
      significantly in their effectiveness, so the treatment of choice should be based
      on clinical considerations. J Orthop Sports Phys Ther 1986;8(2):62-69.

PMID- 18802240
TI  - Case report: the treatment of chronic synovitis by chemical synovectomy.
AB  - Repeated hemarthrosis in hemophiliacs results in early joint destruction. When
      conservative treatment including factor replacement, immobilization, and
      physiotherapy fails to halt the bleeding, chronic synovitis develops and a more
      drastic definitive procedure is required to establish local hemostasis. Various
      techniques including surgical synovectomy, chemical or radioisotopic
      synoviorthesis have been used. We describe the successful rehabilitation and
      return to sport participation of a young boy, once bedridden by ankle synovitis,
      by the use of intraarticular osmic acid. J Orthop Sports Phys Ther 1986;8(2):85
      87.

PMID- 18802241
TI  - Active neck motion measurements with a tape measure*.
AB  - The purposes of this study were to determine if the tape measuring method is a
      reliable method of measuring six active neck motions, to estimate measurement
      errors, and to compare the intratester reliability between an experienced tester
      and an inexperienced tester by using this method. Each tester measured 17
      different normal subjects. Each active neck motion was randomly measured twice.
      The intratester reliability coefficients, determined by correlation analysis,
      ranged from 0.80 to 0.95 for the experienced tester and 0.78 to 0.9 1 for the
      inexperienced tester. The 99% confidence interval for measurement error was
      calculated for each motion. The estimated errors in repeating measurements
      appeared less in the experienced tester than the inexperienced tester. However,
      the intratester reliability did not differ significantly between testers for all
      motions except extension (F = 7.68, p < 0.002). This study indicated that the
      tape measuring method is a reliable means for clinicians to assess neck range of
      motion. J Orthop Sports Phys Ther 1986;8(2):88-90.

PMID- 18802242
TI  - Use of he-ne laser for treatment of soft tissue trauma: evaluation by - gallium
      67 citrate scanning*.
AB  - Sequential quantitative Gallium-67 Citrate (Ga-67) scanning was used to evaluate
      the resolution of inflammation in standardized bruises in rat thighs with and
      without Helium Neon (He-Ne) laser treatment. The severity of inflammation in the
      injured tissue was assessed as the ratio of Ga-67 localized in the bruise to the
      Ga-67 localized in the noninjured area of the same geometry. During the first 12
      days after injury, both (He-Ne laser) treated and nontreated rats healed rapidly
      with no observable differences in Ga-67 localization. J Orthop Sports Phys Ther
      1986;8(2):93-96.

PMID- 18802243
TI  - A Case-Control Study of Running Injuries: Comparison of Patterns-of Runners With
      and Without Running Injuries.
AB  - It has been reported that 70% of runners suffer from injuries at some time during
      their running career, and that the majority of these injuries tend to be
      recurrent. With over 40 million people in the U.S. currently running, an
      understanding of epidemiological factors relating to running injuries may prove
      useful for early recognition and prevention of potential problems. This study
      surveyed 250 runners to determine the prevalence and patterns of running
      injuries; 62% of the sample reported having pain of injuries related to running.
      Runners were divided into two groups based on whether they reported pain or
      injuries related to running in the last 2 years (cases), or were totally
      asymptomatic (controls). The two groups were compared for years run, miles run
      per week, stretching time, involvement in other sports, involvement in strength
      training, and type of running shoes worn. The cases ran slightly more miles,
      spent less time doing supplemental strengthening, and were less involved in other
      sports. The cases spent more time stretching, but had a higher proportion of
      "nonstretchers." There was also a higher proportion of females among the cases.
      The main limitation of the study was the sample size. J Orthop Sports Phys Ther
      1986;8(2):81-84.

PMID- 18802244
TI  - Comparative Study using Four Modalities in Shinsplint Treatments*.
AB  - A question of current interest and debate in physical therapy is the proper
      treatment of shinsplints. Various investigators have espoused the merits of
      different treatment programs for the clinical management of shinsplints. However,
      data comparing the effectiveness of the several methods is limited. This study
      compares the effects of ice massage, ultrasound, iontophoresis, and phonophoresis
      in young adults with a shinsplint syndrome. The results indicate that none of
      these treatment modalities was superior to another; however, all were clearly
      superior to a controlled treatment program. Regression analyses indicated that
      appropriate treatment modalities for shinsplints should be a function of the
      restoration of the individual's range of motion, the number of treatments that
      can be provided, and the availability of the treatment mode. J Orthop Sports Phys
      Ther 1986;8(2):77-80.

PMID- 18802245
TI  - Trunk muscle activity induced by three sizes of wobble (balance) boards.
AB  - The effect on trunk muscle activity of three designs of wobble (balance) boards
      has been investigated electromyographically, in six subjects, in order to define
      the optimal dimensions of a wobble board that will stimulate such muscle
      activity. It is suggested that the dimensions required are a 350-mm diameter
      board set on a ball 50 mm high with a 55-mm radius of curvature, to provide a
      maximum angle of tilt of 15 O. The possible relationship between proprioception
      and lower limb/low back disorders is discussed and the suggestion made that
      wobble boards could be used in clinical trials of coordination training in these
      patients. J Orthop Sports Phys Ther 1986;8(1):27-29.

PMID- 18802246
TI  - Muscular power in young women after slow and fast isokinetic training*.
AB  - The purpose of this study was to determine, via a pilot study, if training at a
      fast isokinetic velocity (180 degrees /sec) would result in a greater increase in
      upper-extremity muscular power than training at a slow isokinetic velocity (60
      /sec) while exercising through a specific range of motion (1 80"). Twenty normal
      young women were randomly selected into one high velocity and one slow velocity
      experimental group. The exercise protocol consisted of four bouts of five maximal
      reciprocal isokinetic contractions of the shoulder flexor and extensor muscle
      groups, three times a week for four weeks. Pre- and post-testing with a Cybex I$
      isokinetic dynamometer was performed to determine if significant power gains were
      elicited within the training range of motion. Aiter training, both fast and slow
      velocity groups showed significant power gains (p < 0.0005). However, the results
      indicated that neither fast nor slow isokinetic training is more effective for
      power production within the 1 80 degrees range of motion of shoulder extension in
      the young women studied. J Orthop Sports Phys Ther 1986;8(1);1-9.

PMID- 18802247
TI  - Pre-employment screening and cardiovascular intervention program.
AB  - Pre-employment screening and health maintenance on the job has been an area of
      concern for both hospitals and industry. Can various disease processes be '
      prevented and can money be saved in the process are some basic questions. A
      program in Akron, OH involving police officers has been set up to examine these
      and other questions. This program is being presented as a model for use in a
      variety of settings since the components have a broad range of application. The
      components include; pre-employment screening, mandatory health standards, and
      comprehensive intervention program. This program has been very successful in
      Akron and it is suggested that the model can have a significant impact in
      business and industrial settings. J Orthop Sports Phys Ther 1986;8(1):42-47.

PMID- 18802248
TI  - Effects of positioning on ankle edema.
AB  - The purpose of this study was to determine the effects of positioning on ankle
      edema during a 20-minute treatment period. Fifty subjects were alternately
      assigned to one of two groups. Members of group A lay supine with their legs
      elevated, group B subjects sat with their legs dependent. Pre- and
      postpositioning volumetric displacements were recorded to determine if a
      significant change occurred. Analysis of covariance testing showed significant
      volumetric difference between groups (p < 0.001). Group A had a significant
      decrease in volume whereas group B had a significant increase in volume. The
      results of this study suggest that physical therapists and athletic trainers
      should no longer attempt to reduce edema with high voltage electrical stimulation
      while their patients sit with their legs dependent. J Orthop Sports Phys The
      1986;8(1):30-33.

PMID- 18802249
TI  - A new musculoskeletal assessment in a student population.
AB  - A common finding in repetition activities (typing, running, swimming . . .), are
      overuse syndromes arising from a mechanical imbalance affecting overstressed soft
      tissues and joints. A more subtle corollary, occasioned by a sedentary life
      style, is an imbalance between postural and phasic muscle groups leading to joint
      dysfunction. Postural and phasic muscles as defined by V Janda (New Zealand Manip
      Ther Assoc Tech Newsletter 2: 1-3, 1977) interplay in complex patterns which
      determine strength and coordination for normal function. Joint pathology, and
      central or peripheral nervous system impairment, all lead to compensatory changes
      in the muscle function, namely the tendency for postural muscles to become tight
      and for phasic muscles to weaken. Faulty posture through muscle imbalance
      compromises joint mechanics predisposing to dysfunction. Appropriate management
      of musculoskeletal disorders should recognize the role of imbalance between
      postural and phasic muscles in both the etiology and sequelae of the disorder. A
      musculoskeletal examination of 35 students was undertaken to develop assessment
      skills, devise a recording form, and refine a test sequence to assist data
      collection. The principal finding of tightness in postural muscles is consistent
      with the theory that these muscles undergo adaptive shortening. This survey
      provided the opportunity to examine the incidence of muscle imbalance in a young
      adult population and to prepare guidelines for future study. J Orthop Sports Phys
      Ther 1986;8(1):34-41.

PMID- 18802250
TI  - Lower Extremity Strength and Active Range of Motion in College Baseball Pitchers:
      A Comparison between Stance Leg and Kick Leg.
AB  - The role of the lower extremities and torso is vital in the pitching mechanism.
      However, a review of the literature reveals information primarily dealing with
      the upper extremity's role in throwing. This pilot study was conducted to: 1)
      determine selected lower extremity strength and range of motion measurements in
      sixteen college baseball pitchers, and 2) compare measurements in the stance leg
      to the kick leg. When preseason profiling is not possible, clinical norms for
      those treating college pitchers can be valuable in proper rehabilitation of the
      lower extremity. Also, by determining trends in lower extremity strength and
      motion when comparing kick (plant) leg to stance (drive) leg, a better
      understanding of lower extremity kinematics in the pitching act can be
      appreciated. Statistically significant differences were found in the active range
      of motion in plantarflexion, hip internal rotation, and hip extension of the
      stance leg, as well as hip flexion of the kick leg. lsokinetic evaluations at
      slow and fast speeds revealed significant differences in the strength of ankle
      dorsiflexors and hip flexors at slow speeds of the kick leg. Strength of the
      hamstrings on the kick leg was significant at fast speeds as was strength of the
      hip external rotators on the stance leg. J Orthop Sports Phys Ther 1986;8(1):10
      14.

PMID- 18802251
TI  - Posterior Cervical Paraspinal Musculature Morphology: A Cadaveric and CT Scan
      Study.
AB  - Positive identification of posterior cervical paraspinal muscles were made on
      computed tomography (CT) scans and correlated with the findings on cadaveric
      cross-sections of corresponding levels. Two frozen, fixed cervical cadaveric
      sections were CT scanned at various levels, then sliced cross-sectionally at the
      appropriate thickness. Individual muscles of the posterior cervical area were
      then identified on the cadaveric section and the corresponding CT scan section.
      In both specimens, identification of the individual muscles was possible on CT
      scan. Detection of normal anatomical variations of the cervical muscles was also
      possible on CT scans, but muscle fiber orientation was not. It is concluded that
      positive identification of posterior cervical paraspinal musculature on CT scan
      is possible. This provides the physical therapist with a greater understanding of
      both cervical cross-section anatomy and gross anatomy of the posterior cervical
      paraspinal musculature. Information obtained through CT scanning can assist the
      physical therapist in treatment of patients with injuries to the soft tissue
      structures of the cervical spine. J Orthop Sports Phys Ther 1986;8(1):15-26.

PMID- 18802252
TI  - Femoral transverse torque: an assessment method.
AB  - This study compared external and internal femoral torques of asymptomatic male
      and female subjects. Peak torque values were recorded using the Cybex(R) II
      isokinetic dynamometer utilizing a prone testing position with the hip in
      neutral. Males produced significantly higher raw peak torques than females in
      both external and internal rotation (p < 0.003). However, when torques were
      normalized to body weight no significant differences were found between male and
      female subjects. External rotation torques were found to be significantly higher
      than internal rotation torques for all subjects combined (p c 0.016). No
      significant difference was found between left and right limbs. The ratio of
      external to internal rotation torque was 1.08 for males and 1.16 for females.
      These ratios are suggested as criterion measures for assessing transverse muscle
      imbalance at the hip joint. J Orthop Sports Phys Ther 1986;7(6):319-324.

PMID- 18802253
TI  - Clinical use of the johnson anti-shear device: how and why to use it.
AB  - The purpose of this paper is to describe the clinical utilization of the Johnson
      Anti- Shear Device. This device presents a method of controlling the anterior
      shear forces developed during isokinetic exercise on a Cybex(R) ll or Orthotrone
      system. The antishear device allows the therapist to alter the amount of anterior
      shear developed during exercise, thus allowing the therapist to individualize the
      rehabilitation protocol. This is of special significance following anterior
      cruciate injury. The clinical use of this device will allow the therapist to more
      safely develop quadriceps exercise programs with their anterior cruciate
      deficient knee patients. J Orthop Sports Phys Ther 1986;7(6):304-309.

PMID- 18802254
TI  - The effect of high volt galvanic stimulation on quadriceps femoris muscle torque.
AB  - Nineteen healthy subjects participated in this study to determine the
      effectiveness of high voltage galvanic (HVG) stimulation in producing contractile
      force of the quadriceps femoris muscles. Each subject was asked to perform a
      maximal voluntary isometric contraction (MVC) followed by HVG stimulation. During
      each of the three testing sessions, the subject was maximally stimulated with
      either a 50, 80, or 120 pps stimulus. Comparisons were then made between the
      torque force generated by a MVC and HV stimulated contractions. The results
      indicated that the HVG stimulation was capable of producing contractile forces
      from 17 to 85% of a MVC, with no significant difference between the three,
      frequencies in their effectiveness. This study suggests that HVG stimulation is
      capable of producing a "training stimulus" required for muscle strengthening. J
      Orthop Sports Phys Ther 1986;7(6):314-318.

PMID- 18802255
TI  - Hamstring weakness after surgery for anterior cruciate injury.
AB  - The purpose of this study was to measure the effects of surgery and
      immobilization on the isometric strength of the hamstrings. Fifteen male
      volunteers were measured for isometric hamstring torque prior to surgery for
      correction of anterior cruciate ligament (ACL) insufficiency. After surgery the
      subjects were casted for 6 weeks and did not perform exercises specific to the
      hamstrings. Subjects were retested immediately after cast removal and the
      hamstring output was compared to the preoperative hamstring output. A 43%
      decrease in hamstring torque was noted which is statistically significant (p <
      0.001). It is suggested that exercise of the hamstring, a muscle group of great
      importance to the ACL-injured knee, during immobilization may be helpful in
      limiting hamstring strength loss during the immobilization period. J Orthop
      Sports Phys Ther 1986;7(6):310-313.

PMID- 18802256
TI  - Validation of the Johnson Anti-Shear Accessory as an Accurate and Effective
      Clinical lsokinetic Instrument.
AB  - This article reports two separate investigations into the validity of the Johnson
      Anti- Shear Accessory (JASA) as an isokinetic evaluation and exercise instrument.
      Experiment I attempted to verify the shear prevention aspect of the device on 10
      anterior cruciate ligament injury patients and experiment I1 sought to establish
      the testing accuracy of the tool in comparison to the standard Cybex(R) knee
      input shaft (CKIS) on a qualified sample of eight subjects. A Cybex II-CDRC
      system protocol of five test knee extension/flexion repetitions at velocity
      spectrum speeds of 60, 120, 180,240, and 300 degrees /sec, preceded by a warm-up
      of three gradient submaximal and one maximal repetitions, was used for both
      studies. The null hypothesis was rejected in experiment 1 as an ANOVA test
      revealed significant factoral differences and Pearson correlation tests showed
      noncomparison between the JASA (r = 0.79 quadriceps, r = 0.89 hamstrings) and the
      CKIS (r = 0.23 quadriceps, r = 0.91 hamstrings) relative to the design control.
      The null hypothesis was accepted in experiment I1 as ANOVA testing failed to show
      a significant factoral difference while the JASA and CKIS demonstrated strong
      correlations (r = 0.97 quadriceps, r = 0.99 hamstrings). It was concluded that
      the JASA effectively controls anterior tibial shear during isokinetic activity
      and that the JASA is an accurate and valid isokinetic evaluation and exercise
      device. J Orthop Sports Phys Ther 1986;7(6):298-303.

PMID- 18802257
TI  - Survey of Orthopaedic Residents' Exposure to Physical Therapy during Residency.
AB  - The purpose of this study was to assess orthopaedic surgery residents' exposure
      to physical therapy in their training to date. A questionnaire was sent to 30
      orthopaedic residents at two residency programs in Kentucky. The residents'
      clinical and didactic exposure to physical therapy, their knowledge of the
      therapist's educational background, the significance of physical therapy to their
      orthopaedic patients, and their confidence in the therapist's skills were
      assessed by the questionnaire. Twenty five of the residents responded and
      frequency distributions were used to assess the data. Twenty-one residents had no
      courses or in-services in medical school or residency that discussed how physical
      therapy is useful to their patients, yet only 13 residents perceived an
      inadequacy in their knowledge of physical therapy. The residents were well
      informed of the therapist's educational background, yet 6 residents believed that
      the education for a therapist was insufficient to enable the therapist to choose
      a specific treatment for orthopaedic patients. J Orthop Sports Phys Ther
      1986;7(6):335-338.

PMID- 18802258
TI  - Age-related differences in the human sacroiliac joint: a histological study; -
      implications for therapy.
AB  - Sacroiliac joint dysfunction often is implicated in the etiology of low back
      pain. Few data exist on age differences in sacroiliac tissues. The purpose of
      this study was to identify by light microscopy the differences that exist between
      age decades. Joints from 36 fetuses and 15 adult cadavers were excised and
      prepared in the routine manner. In fetal joints, complete cavitation was not
      observed before 34 weeks of age; the iliac surface was predominantly fibrous or
      fibrocartilage. Fibrous bands connected joint surfaces even in term specimens.
      All adult specimens showed degenerative changes which included incomplete fibrous
      (N = 9) or chondroid (N = 5) ankylosis and incompletely healed, presumed
      fractures of the joint surface (N = 6). On the average, sacral cartilage was 1.7
      times thicker than the iliac "cartilage." The potential for the older sacroiliac
      joint to be affected by techniques of manual therapy is questionable given the
      degenerative features observed. J Orthop Sports Phys Ther 1986;7(6):325-334.

PMID- 18802259
TI  - Strength relationship of the knee musculature: effects of gravity and sport*.
AB  - The purposes of this study were to examine the effects of gravity and sport on
      the hamstrings-quadriceps strength relationships. The peak torques at four speeds
      of isokinetic exercise (60, 180, 240, 300 degrees /sec) were determined for 20
      male college track athletes, including 10 sprinters and 10 distance runners. The
      runners were tested on a Cybex(R) II isokinetic dynamometer. Peak torque
      measurements were corrected for the effects of gravity. Results of the present
      study showed that: 1) the effects of gravity significantly alters the hamstrings
      to quadriceps ratio at all velocities, and 2) there is no statistically
      significant difference in the hamstrings quadriceps strength ratios between the
      two groups of athletes except at 300 O/sec. At that speed, sprinters had a higher
      ratio than distance runners. J Orthop Sports Phys Ther 1986;7(5);232-235.

PMID- 18802260
TI  - In vivo approximations of the classic in vitro length-tension relationship: an
      isokinetic evaluation.
AB  - Several biarticular muscles of the human lower extremity were placed in various
      positions of stretch, using a hinged board to alter trunk-thigh relationships in
      59 young adult volunteers of both sexes. Prior measurement, by direct x-ray of
      one subject on the test apparatus and by use of an articulated skeleton placed in
      the same pelvofemoral orientations as seen on the x-rays, supports the conclusion
      that the test positions of these 59 subjects were such that the biarticular
      extensor (rectus femoris) and flexors, (biceps femoris, semimembranosus and
      semitendinosus) were in fact being shortened or lengthened as desired under the
      prescribed positioning protocol. Isokinetic torques, total work output,; and
      average power production were obtained for maximal knee extensions and flexions
      through the full anatomical range of motion. The results support an assertion of
      close in vivo approximation to the classic in vitro length-tension relationship.
      J Orthop Sports Phys Ther 1986;7(5):222-231.

PMID- 18802261
TI  - Evaluation of two ankle appliances using ground reaction force data.
AB  - The purpose of this study was to evaluate, using ground reaction force data, two
      ankle stabilizing techniques commonly used by athletic trainers; the closed
      Gibney taping procedure and the boot type ankle stabilizer. Each condition was
      examined in a pre- and postexercise bout. In addition, a no appliance condition
      was also tested. Eight healthy female athletes were required to perform ten
      satisfactory trials in each of the five conditions. Ten trial mean values of 34
      descriptors of ground reaction force components for each subject/condition were
      evaluated using multivariate analyses of variance. No significant differences in
      any of the force or impulse variables were found across conditions. However,
      significant differences were found in three variables describing the relative
      timing of events in the footfall (p < 0.05). No significant differences were
      found between the pre- and postexercise conditions. The variability in the
      measured parameters. of the no appliance condition was consistently higher than
      the ankle appliance conditions. The implication of the study was that, in normal
      running, the ankle appliances did not appear to moderate or change foot function.
      J Orthop Sports Phys Ther 1986;7(5):244-249.

PMID- 18802262
TI  - Manipulation in the treatment of tennis elbow.
AB  - With the increasing popularity of tennis there has been an increasing interest in
      the etiology and treatrnent of lateral epicondylitis. The current pathophysiology
      is assumed to be related to repeated wrist extension and rotation leading to
      microtrauma at the common wrist extensor origin with an ultimate change in the
      histology of the area. Treatment involves exercise, the use of many modalities to
      treat the area locally, and more specifically when tennis is the etiology a whole
      variety of functional adaptations as well as a modification of equipment.
      Specifically, manipulation of the elbow has played a large role in the treatment
      of resistant tennis elbow and the large number of different named maneuvers has
      led to a certain amount of confusion. The second half of the paper attempts to
      review these manipulations including that described by Mills, Cyriax, Kaltenborn,
      Mennell, and Stoddard. These manipulations seem to fall into two basic varieties:
      those that seek full extension and those that will produce a varus thrust. The
      manipulations done with the elbow in extension and the forearm in pronation have
      the greatest chance of affecting the contractile elements whereas those performed
      with a varus thrust at the elbow seem to act primarily on the capsular structures
      causing gapping and restoring joint play. While manipulation may be effective it
      always must be used in conjunction with a total treatment regime including
      exercise, modalities, and modification of the activities involved in the
      etiology. J Orthop Sports Phys Ther 1986;7(5):264-272.

PMID- 18802263
TI  - Sports physical therapy specialization.

PMID- 18802264
TI  - Proprioceptive neuromuscular facilitation versus weight training for enhancement
      of muscular strength and athletic performance*.
AB  - This study was designed to examine the effects of proprioceptive neuromuscular
      facilitation (PNF) and weight training (WT) on muscular strength and athletic
      performance. Thirty college women were randomly assigned to one of three groups:
      WT, PNF, and control. WT and PNF subjects trained 3 days a week for 8 weeks. All
      subjects were tested for changes in knee and elbow extensor strength, throwing
      distance, and vertical jump. The WT group increased strength by 19.3% for knee
      extension and 20.4% for elbow extension while the PNF group increaseil22.1 and
      29.1 %, respectively. PNF also increased throwing distance by 25% and vertical
      jump by 16% while WT had increases of 12.8 and 9.9% respectively. These findings
      indicate PNF might be superior to WT in athletic performance enhancement and,
      therefore, the better modality for athletic conditioning and injury
      rehabilitation. J Orthop Sports Phys Ther 1986;7(5):250-253.

PMID- 18802265
TI  - Clinical observations with respect to progressive/ regressive traction.
AB  - The objectives of the report were to test a theory advanced by one of our
      patients and practiced manually in the physical therapy department: that the
      effects of cervical traction would be enhanced if the tractive force were to be
      applied incrementally instead of the usual standard method. Tests with patients
      indicated that the theory had considerable merit. Incremental-force
      (progressive/regressive) traction machines are now being manufactured to provide
      tissue accommodation for more effective use of spinal traction. J Orthop Sports
      Phys Ther 1986;7(5):261-263.

PMID- 18802266
TI  - The effects of inversion traction on spinal column configuration, heart rate,
      blood pressure, and perceived discomfort.
AB  - The therapeutic effectiveness of inversion traction has only recently come under
      investigation. The purpose of this study was to use noninvasive methods to
      determine traction, cardiovascular, and perceived effects of inversion. The
      Gravity Gym(R) and Gravity Boot(R) inversion systems were compared. Treatment
      order was randomized and 18 normal subjects between the ages of 22 and 31 were
      suspended in each inversion device for 7 minutes. A computerized method was used
      for assessing posture. Three-dimensional coordinates were determined for spinous
      processes C7 through L5 relative to the midpoint of a line drawn between
      posterior superior iliac spines (S2). Heart rate was palpated and blood pressure
      was recorded using a standard sphygmomanometer. Pre-, initial, late, and
      postinversion measurements were taken. Questionnaires administered following each
      inverted posture assessed levels of discomfort. One-way analysis of variance was
      conducted to test the significance of results (p < 0.05). Measurements for both
      systems revealed an increase in L5-S2 distance, a decrease in C7-T12 distance,
      and a decrease in depth of the thoracolumbar curves. Segments C7-S2, L 1 -S2, L 1
      -L2, L3-L4, and L4-L5 were increased in length by the Gravity Gym but not the
      Gravity Boots. Heart rate decreased and blood pressure increased an average of 20
      mm Hg for both systems as subjects were inverted. This pattern was observed
      throughout the inversion period. Upon return to stand, heart rate increased for
      both systems while blood pressure decreased only for the Gravity Boot system.
      Subjects indicated that the Gravity Gym was the more tolerable inversion system.
      lnversion can be an effective means of spinal traction but due to elevated blood
      pressure, inversion may be contraindicated for some patients.J Orthop Sports Phys
      Ther 1986;7(5):254-260.

PMID- 18802267
TI  - Muscular strength and temporomandibular joint repositioning.
AB  - The relationship between physical performance and the position of the
      temporomandibular joint has received much attention in the past few years. Some
      studies have shown improvement in the physical performance with the proper
      alignment of the jaw. However, most of these studies lack proper experimental
      design. This study used a double blind and placebo design. All subjects
      experienced to some degree improper alignment of the temporomandibular joints.
      After establishing baseline data, no significant differences were found in grip
      strength, maximum peak torque for knee extension/flexion, or total work for knee
      extension/flexion. Therefore, we feel that changing the position of the temporal
      mandibular joint does not increase muscular strength. J Orthop Sports Phys Ther
      1986;7(5):236-239.

PMID- 18802268
TI  - lsokinetic Shoulder Strength of High School and College-Aged Pitchers*.
AB  - The purpose of this study was to determine the isokinetic strength of the
      shoulders of high school and college-aged baseball pitchers. Twenty-four athletes
      ranging from 14 to 21 years of age volunteered for this study. The Cybex(R) II
      and U.B.X. T. were utilized to test the strength of the shoulder
      abductors/adductors, flexors/extensors, horizontal abductors/adductors, and
      external/internal rotators at 90, 120, 2 10, and 300 degrees /sec. There were no
      consistent differences between dominant and nondominant arm strength, except for
      the shoulder adductors and shoulder extensors. The shoulder abductors and flexors
      were approximately 50% as strong as the adductors and extensors, respectively.
      There was a 1:1 ratio between the horizontal abductors/ adductors. The external
      rotators were approximately two-thirds as strong as the internal rotators. A
      positive correlation was found between total body weight and shoulder strength.
      This information is relatively new to the literature and should provide
      clinicians with some training and rehabilitation guidelines. J Orthop Sports Phys
      Ther 1986;7(4):163-172.

PMID- 18802269
TI  - Kinematic effects of heel lift use to correct lower limb length differences*.
AB  - The effect of the heel lift to correct a limb length difference was studied by
      electrogoniometry (elgons) in four male subjects with a limb length inequality
      between 3/~6 inch (0.48 cm) and 3h inch (0.95 cm). Six elgons were attached to
      bilateral hip, knee, and ankle joints as the subject walked (3 mph) and jogged (6
      mph) on the treadmill twice, once with the heel lift and once without. Recordings
      from the elgons examined maximal flexion and extension during support and swing
      phase, amplitude of movement (ROM), duration of each movement, and angular
      velocity of each joint. Within the limitations of the study, the following
      conclusions were drawn: 1) the addition of a heel lift did not appear to
      significantly affect biomechanical measures of gait; and 2) insertion of a heel
      lift did tend to cause more symmetrical movement for the maximum angle of hip
      extension and ROM of the swing plantarflexion phase of the ankle but more
      asymmetrical ROM of the swing flexion phase of the knee. J Orthop Sports Phys
      Ther 1986;7(4):173-179.

PMID- 18802270
TI  - Dancers' spinal syndromes.
AB  - Low back syndromes in dancers are intimately related to flaws in the dance
      technique, especially postural faults and incorrect movements into hyperextension
      of the hip. The pathology produced by the technical faults is multiplied in those
      dancers whose physiques are not ideally suited to withstand the stresses of
      classical training. A thorough understanding of the biomechanical aspects of the
      dance technique is essential to prevent and rehabilitate these low back syndromes
      in dancers. J Orthop Sports Phys They 1986;7(4):180-191.

PMID- 18802271
TI  - Fatigue Response in Human Quadriceps Femoris Muscle during High Frequency
      Electrical Stimulation*.
AB  - The purpose of this study was to examine the fatigue response of the quadriceps
      femoris muscle to two patterns of high frequency alternating electrical current.
      Muscle fatigue was evaluated by the comparison of isometric torque fluctuations
      during the 10-minute application of both stimulus patterns. Muscle fatigue was
      also assessed during an isokinetic fatigue test which immediately followed both
      stimulation patterns. The results indicated that greater amounts of electrical
      stimulation produced lower current-induced contraction intensities with a greater
      amount of fatigue. During the isokinetic fatigue test, smaller (P < 0.01)
      exponential peak torque declines were observed following greater amounts of
      electrical stimulation. This suggested that high frequency current may
      selectively fatigue fast twitch (FT) muscle fibers. Therefore, it was concluded
      that selective stimulation of FT muscle fibers may be an important component
      explaining the mechanism of strength increases following application of high
      frequency alternating current. J Orthop Sports Phys Ther 1986;7(4):145-153.

PMID- 18802272
TI  - Case study: a treatment approach for a resistant knee extension contracture.
AB  - A function-limiting knee extension contracture following an intra-articular femur
      fracture was treated with traditional conservative and surgical intervention
      without satisfactory results. A new treatment program was planned which included
      a combination of heat, ice, prolonged passive stretch, and exercise. The patient
      regained functional knee flexion and was able to return to preinjury athletic
      activities. The treatment protocol described offers a time consuming, but
      effective approach to treating knee extension contractures resistant to surgical
      and traditional conservative management. J Orthop Sports Phys Ther 1986;7(4):159
      162.

PMID- 18802273
TI  - Case Study: Rehabilitation of a Surgically Repaired Medial Collateral Knee
      Ligament Using a Limited Motion Cast and lsokinetic Exercise*.
AB  - Recent studies indicate that early mobilization of surgically repaired collateral
      ligaments leads to a more rapid gain in tensile strength compared to immobilized
      ligaments. Other advantages of early mobilization include prevention of muscle
      atrophy, joint stiffness, and articular cartilage fibrillation. Because of these
      observations, a professional Australian Rules footballer with a complete rupture
      of the right medial collateral ligament of his knee joint, was commenced, after
      surgical repair, on an early controlled mobilization program using a limited
      motion cast (LMC) and isokinetic exercise. Rehabilitation was commenced after 2
      weeks of immobilization in a LMC, and progressed through four stages, all coupled
      with isokinetic exercise. Weeks 2-6, exercise in LMC through 20-60 degrees ;
      weeks 7-8, exercise out of LMC through 15- 1 OOO; weeks 8-9, exercise through a
      full range of movement, 0-130'; weeks 10- 12, exercise through a full range plus
      inner range 0-30' repetitions. The footballer returned to full competition
      approximately 12 weeks postsurgery with no medial collateral laxity and almost
      normal Cybex IP parameters. J Orthop Sports Phys Ther 1986;7(4):154-158.

PMID- 18802274
TI  - lron Deficiency in Athletes: Consequence or Adaption in Strenuous Activity.
AB  - Recent, more sensitive measures of iron status indicate a prevalence of iron
      deficiency, with or without anemia, among young women, children, and adolescent
      males participating in strenuous physical activity. Anemia primarily restricts
      brief, intense exercise; whereas iron deficiency limits performance of endurance
      activities. The impact of iron deficiency on oxidative capacity of muscle,
      protein synthesis, growth, behavior, and body temperature regulation are
      reviewed. The widespread effects of iron deficiency warrant closer attention to
      the iron status of athletes and the practice of dietary iron supplementation in
      the intervention and prevention of iron deficiency. J Orthop Sports Phys Ther
      1986;7(4):192-195.

PMID- 18802275
TI  - A Preliminary Investigation: History, Physical, and lsokinetic Exam Results
      versus Arthroscopic Diagnosis of Chondromalacia Patella *.
AB  - The purpose of this pilot study was to identify those clinical exam findings most
      often seen in patients with a positive chondromalacia patella (CMP) arthroscopic
      exam. Twenty patients with a clinical diagnosis of CMP or meniscal lesions (M) or
      both (CMP+M) were evaluated by two physical therapists using the history,
      physical, and Cybex(R) II isokinetic testing data. More than 50% of the patients
      with arthroscopically confirmed CMP complained of peripatellar pain, pain with
      ascending and descending stairs, and pain with prolonged flexion. At least 50% of
      these patients also demonstrated pain with a patellar grinding test and crepitus
      during the active knee extension test. Chi square analysis of the clinical exam
      data between the arthroscopically diagnosed CMP+M patients and 20 age- and sex
      matched normal subjects revealed a significant difference in response to the
      three history questions analyzed. No significant differences were found on the
      physical exam, including Cybex II isokinetic testing results. Our findings
      demonstrate the significant role of the history in diagnosing symptomatic CMP.J
      Orthop Sports Phys Ther 1985;7(3):115-123.

PMID- 18802276
TI  - Biomechanical analysis of the foot and ankle for predisposition to developing
      stress fractures.
AB  - Forty-seven subjects were studied to discover predisposing factors for their
      radiologically diagnosed metatarsal stress fractures. Biomechanics of the foot
      and ankle were introduced to help explain forefoot varus, abnormal rearfoot
      valgus, and dorsiflexion as intervening variables in metatarsal stress fracture
      development. Results concluded that subjects with forefoot varus and decreased
      dorsiflexion had 8.3: 1 and 4.6: 1, respectively, odds of developing a metatarsal
      stress fracture. Abnormal rearfoot valgus had no significant effect on
      predisposing the subjects to develop a stress fracture. J Orthop Sports Phys Ther
      1985;7(3):96-101.

PMID- 18802277
TI  - Exercising isokinetically: seated shoulder variations.
AB  - Equipment "set-up" time must be kept to a minimum. Although equipment is
      available to rehabilitate the shoulder, often it is not utilized because of the
      time it takes to prepare. The use of a low stool can expedite set-up time and
      allow a vigorous workout for the orthopedic andlor sports medicine patient. J
      Orthop Sports Phys Ther 1985;7(3):124-126.

PMID- 18802278
TI  - Objective evaluation of peroneal response to sudden inversion stress.
AB  - The purposes of this paper are to describe an objective technique developed to
      assess the dynamic response of the peroneal muscles to a sudden inversion motion
      and to report the results obtained from testing injured and noninjured ankles. A
      platform was constructed to drop the ankle into a controlled degree of inversion
      while measuring the time to peroneal response and the angular rotation. Thirty
      volunteers were tested, 15 of whom had experienced a unilateral ankle sprain 3-
      10 months prior to testing. Results show a trend toward delayed peroneal response
      and greater angular displacement at the time of peroneal response in injured
      ankles but analysis of variance showed no significant difference. The total
      angular displacement in the injured ankles was significantly greater. This
      objective technique could be used to evaluate treatment regimens and, by testing
      ankles soon after injury and serially, to evaluate readiness to return to
      activity. J Orthop Sports Phys Ther 1985;7(3):107-109.

PMID- 18802279
TI  - Normal biomechanics of the foot and ankle.
AB  - The biomechanics of the foot and ankle are important to the normal function of
      the lower extremity. The foot is the terminal joint in the lower kinetic chain
      that opposes external resistance. Proper arthrokinematic movement within the foot
      and ankle influences the ability of the lower limb to attenuate the forces of
      weightbearing. It is important for the lower extremity to distribute and
      dissipate compressive, tensile, shearing, and rotatory forces during the stance
      phase of gait. Inadequate distribution of these forces could lead to abnormal
      stress and the eventual breakdown of connective tissue and muscle. The combined
      effect of muscle, bone, ligaments, and normal foot biomechanics will result in
      the most efficient force attenuation in the lower limb. This article will look
      specifically at the normal biomechanics of the foot and ankle. J Orthop Sports
      Phys They 1985;7(3):91-95.

PMID- 18802280
TI  - Comparative radiological study of the influence of ankle joint strapping and - -
      taping on ankle stability*.
AB  - A comparative radiological study was carried out to test the stabilizing value of
      ankle strapping and taping on unstable tibiotalar joints. Unstable ankle joints
      of 51 sportsmen were examined without bandages, with strapping, and with taping
      before and after an activity program. The use of taping proved to give the
      greatest decrease of the talar tilt angle. This improvement was still greater,
      even after activity, than the stabilization obtained by strapping, before any
      activity. J Orthop Sports Phys Ther 1985;7(3):110-114.

PMID- 18802281
TI  - Mechanical pull of the peroneal tendons on the fifth ray of the foot.
AB  - The purpose of this study was to measure the deflection angle of both peroneal
      tendons as they turn around the lateral malleolus. A reduction of the angle
      occurs when the subject stands on tip-toes, in the manner of dancers and
      sprinters. This reduction of deflection angle leads to higher mechanical
      efficency. Female subjects were found to be superior to males in their ability to
      plantarflex the ankle, straightening out their tendons more than do men. The
      traditional approach to exercising muscles around the ankle ignores the varied
      mechanical situations which occur during the practice of sports. The data
      presented should provide guidelines for rehabilitation programs of the injured
      ankle and lateral border of the foot. J Orthop Sports Phys Ther 1985;7(3):102
      106.

PMID- 18802282
TI  - Muscular fitness profile of female college basketball players.
AB  - The purpose of this investigation was to describe the body composition, peak
      torque, peak torque ratios, and relative and absolute muscle endurance in the
      ankle, knee, shoulder, and elbow of 13 female college basketball players. A
      Cybex(R) II isokinetic dynamometer was used to assess joint torque. Results
      indicated that 1) these subjects were taller, heavier, and leaner than untrained
      females of the same age; 2) the flexors were stronger than the extensors at each
      joint and at each velocity tested with the exception of the right elbow; 3) the
      right-left difference in peak torque ranged from 0.2 to 12.4% with the mean
      difference across all joints and all velocities 3.0%; 4) f1exor:extensor ratios
      varied with the velocity of the movement; and 5) relative muscle endurance was
      greatest in the shoulders and least in the knee while absolute muscle endurance
      was greatest at the knee and lowest at the ankle. J Orthop Sports Phys Ther
      1985;7(2):59-64.

PMID- 18802283
TI  - A strength study utilizing the electro-stim 180.
AB  - lncreased interest has developed in the use of electrical stimulation as either
      an adjunct or a substitution for voluntary muscle contraction as a technique to
      improve strength in normal individuals. This study was conducted in an attempt to
      determine if electrical stimulation does significantly increase the strength of
      normal musculature. A sample using 17 normal subjects (1 0 male, 7 female) with
      an average mean age of 26 years was obtained. In this study the subjects were
      divided into two groups. Three different speeds (0, 60, and 240 degrees /sec)
      with 3-5 contractions at each speed were used to determine the maximum strength
      of each subject's nondominant leg as measured by a Cybex(R) II dynamometer. Group
      A consisted of 8 subjects (3 male, 5 female) who served as a control group. Group
      B consisted of 9 subjects (7 male, 2 female) who received electrical stimulation
      to the nondominant leg for 20 treatment sessions (5 days/week for 4 weeks).
      Results indicate that group B did have a significant strength gain which was
      achieved after 4 weeks of stimulation. These results were only significant at an
      isometric mode (OO/sec) and did not carry over to dynamic measurement. J Orthop
      Sports Phys Ther 1985;7(2):50-53.

PMID- 18802284
TI  - Peak torque values of the knee extensor and flexor muscles of females.
AB  - Two hundred and forty-one females between the ages of 18 and 28 years were
      subjects for this study. Subjects were tested for knee extension and knee flexion
      on a Cybex(R) II isokinetic dynamometer at 60 degrees /sec using a modified
      seating arrangement which placed the back rest at 20 from the vertical. To
      familiarize subjects with the Cybex II, two practice trials of complete extension
      and flexion were allowed. The actual test included four consecutive trials of
      voluntary maximum isokinetic contractions of the knee extensors and flexors. The
      mean torque value of the knee extensors was 96.47 ft-lb and 51.77 ft-lb for the
      knee flexors. The corresponding ratio was 1.86: 1.00. The trials demonstrating
      the maximum peak torque values for the knee extensors and flexors were chosen to
      determine the time to peak torque. The mean time to peak torque for the knee
      extensors (2.76 sec) was only slightly longer (0.02 sec) than the mean time to
      peak torque for the knee flexors (2.78 sec). Based on the outcome of the
      investigation and the size of the sample, it is suggested that young and
      untrained women who have no history of health-related conditions of the knee
      demonstrate an approximate ratio of knee extensor strength to knee flexor
      strength of 2: 1 at 60 /sec. J Orthop Sports Phys Ther 1985;7(2):65-68.

PMID- 18802285
TI  - Alternative cybex exercise positions.
AB  - Many alternative exercise positions are possible with the Cybex(R). The most
      practical of these positions are presented. Clinicians are encouraged to test and
      adopt these variations if they are deemed appropriate and useful for their
      facility and patient clientele. J Orthop Sports Phys Ther 1985;7(2):73-76.

PMID- 18802286
TI  - Bioelectricity and bone healing.
AB  - The purpose of this paper is to acquaint rehabilitation personnel with the three
      types of commercial devices that use electricity to restimulate osteogenesis in
      nonunion fractures and other conditions. This background is important for the
      careful planning of the rehabilitation for these unique patients. These patients
      may not have used the involved extremity for a long period prior to resolution.
      The main problem will be osteoporosis. The modality of bioelectricity offers new,
      exciting possibilities for future applications in other tissues besides bone as
      well. J Orthop Sports Phys Ther 1985;7(2):54-58.

PMID- 18802287
TI  - Descriptive Measures of lsokinetic Trunk Testing.
AB  - Measurements of isokinetic parameters during trunk flexion and extension were
      collected for 44 untrained adult subjects (23 females, 21 males) using a Cybex(R)
      11 dynamometer and trunk stabilization system interface to a Cybex Data Reduction
      Computer. On each of three days, subjects performed two sets (trials) of maximal
      extension/flexion contractions. One trial consisted of four repetitions each at
      the isokinetic speeds of 30, 60, 90, and 120 degrees /sec. Data interpretation
      consisted of: Peak torque, range of motion from the initiation of contraction to
      peak torque, total range of motion, total work performed, total power generated,
      torques produced relative to body weight, and flexion/extension torque and work
      ratios. It was concluded that isokinetic testing of the trunk can provide
      clinically useful guidelines for trunk evaluation and rehabilitation when a large
      data base is collected for subject populations with various physical
      characteristics. J Orthop Sports Phys Ther 1985;7(2):43-49.

PMID- 18802288
TI  - Biomechanics of the foot in walking: a function approach.
AB  - The physical therapist has recognized the importance of evaluating foot and ankle
      function in patients who have spinal and lower extremity dysfunction. The ability
      to properly evaluate a joint requires a thorough understanding of the
      biomechanics of the involved articulations. This paper presents the clinician
      with a concise explanation of the biomechanical functions required of the foot
      during the walking cycle. A detailed description of two of the primary joints
      responsible for performing these functions are also reviewed. J Orthop Sports
      Phys Ther 1985;7(2):69-72.

PMID- 18802289
TI  - Clinical presentation of osgood- schlatter disease in the adolescent population.
AB  - Osgood-Schlatter disease is a condition affecting knees of adolescents. Males are
      affected more frequently than females, and unilateral involvement is more common
      than bilateral. In the 75 cases seen in our clinic in 4l/3 years, participation
      in basketball was twice as common among our patients as was any other sport. With
      the addition of our clinical cases to those documented in the literature, the
      left knee is significantly more involved than the right (P < 0.05). Relationship
      to hand dominance is discussed as a possible explanation for the unusual
      prevalence for left knee involvement. J Orthop Sports Phys Ther 1985;7(1):1-4.

PMID- 18802290
TI  - Osgood-schlatter disease: review of literature and physical therapy management.
AB  - Osgood-Schlatter disease is a traction apophysitis of the tibial tubercle, the
      weakest link of the extensor mechanism of the adolescent. Conventional medical
      treatment includes plaster casting, injections of various anti-inflammatories,
      and surgical removal of painful ossicles in resistant cases. While not a very
      common condition, Osgood-Schlatter disease is being seen with increasing
      frequency in teenage athletes, especially basketball players (Antich, Lombardo, J
      Orthop Sports Phys Ther 7: 1-4, 1985.) With a focus on muscular tightness as a
      possible causative factor, physical therapy evaluation is outlined, followed by
      techniques for pain control and stretching exercises for the quadriceps and
      hamstrings. Ice massage is advocated as a way for the athlete to treat
      postexertional discomfort in the area of the tubercle. The patient and his or her
      parents must be assured that while residual deformity may remain, disappearance
      of symptoms coinciding with closure of the apophyseal plate is often the end
      result.J Orthop Sports Phys Ther 1985;7(1):5-10.

PMID- 18802291
TI  - Conservative management of peripheral nerve injuries utilizing selective
      electrical stimulation of denervated muscle with exponentially progressive - -
      current forms.
AB  - One objective of the conservative management of peripheral nerve injuries is to
      delay and minimize denervation atrophy of the muscle parenchyma. A properly
      administered program of selective electrical stimulation of denervated muscle may
      appreciably delay denervation atrophy. Current forms having slowly increasing
      intensities (exponentially progressive currents) are capable of selective
      stimulation of denervated muscle while awarding the stimulation of both the
      innervated muscles and the intact sensory nerves. The present paper discusses the
      rationale for the utilization of selective electrical stimulation of denervated
      muscle following peripheral nerve injuries.J Orthop Sports Phys Ther 1985;7(1):11
      15.

PMID- 18802292
TI  - Rugby Injuries Sustained during Tournament Play.
AB  - Rugby football is a fast growing physical contact sport that is known for its
      ruggedness and injuries. Tournament play tests the stamina of the individual
      players and may have a cumulative wear and tear effect that results in different
      types of injuries. This study was conducted to determine what body parts are
      injured in a rugby tournament and how serious those injuries are. Climatic
      conditions, mainly heat and humidity, were considered to be major factors. Heat
      related injuries were the single most important cause for termination of play.
      This type of injury is very serious and may be reduced or prevented by following
      simple guidelines for play based on the temperature-humidity index. Most other
      injuries were strains, sprains, contusions, and several lacerations to the knee,
      thorax, head, and neck; none was catastrophic. The reputation that rugby football
      is brutal does not seem justified by the injuries sustained in this tournament. J
      Orthop Sports Phys Ther 1985;7(1):16-19.

PMID- 18802293
TI  - Distal femoral stress fracture in military basic trainees: a report of three
      cases*.
AB  - The distal femoral stress fracture can be very difficult to diagnose. Complaints
      include vague hip, thigh, or knee pain, aching at night, increased pain with
      weightbearing, and swelling about the knee. It is imperative that this stress
      fracture be diagnosed in a timely manner because it can result in a displaced
      fracture of the femur. J Orthop Sports Phys Ther 1985;7(1):20-22.

PMID- 18802294
TI  - II: A New Dimension in Cybex Rehabilitation.
AB  - Cybex(R) isokinetic exercise equipment is rapidly becoming an invaluable weapon
      in the sports medicine practitioner's arsenal. This unique equipment lends itself
      to the broad spectrum of patient treatment. With the introduction of the
      Orthotron these capabilities have been expanded. These additional capabilities
      utilize creativity with the combined features of the Cybex II, U.B.X.T.(R), and
      Orthotron II.J Orthop Sports Phys Ther 1985;7(1):23-24.

PMID- 18802295
TI  - A comparison of muscular tightness in runners and nonrunners and the relation of
      muscular tightness to low back pain in runners.
AB  - The focus of this experimental study was to compare muscular tightness at the hip
      between runners and nonrunners, and to determine if there is a relation between
      muscular tightness and low back pain in runners. Goniometric range of motion
      measurements of three hip movements, abduction, flexion with the knee extended,
      and extension, were taken on two subject populations, runners (N = 45), and
      nonrunners (n = 43), in order to determine tightness of the hip adductor,
      extensor, and flexor muscles, respectively. The mean score values obtained for
      each of the three measurements for both the right and left sides were compared
      for differences between the running and nonrunning populations and between male
      and female subjects. Runners were found to be significantly limited in the
      movement of hip flexion with the knee extended. The mean score values obtained
      for all male subjects for this movement were lower than those for all female
      subjects. The incidence of low back pain in runners was examined; however, no
      correlation could be drawn between muscular tightness in these subjects and low
      back pain. J Orthop Sports Phys Ther 1985;6(6):315-323.

PMID- 18802296
TI  - Quadriceps torque and integrated electromyography*.
AB  - Using surface electromyography, the myoelectric activity and torque of the
      quadriceps muscles were recorded under isometric conditions. The purpose of the
      study was to identify the optimal angle of knee flexion for normalization
      purposes. Additionally, the behavior of the quadriceps as the knee was flexed was
      investigated. It was found that the subject's sex may affect the angle at which
      maximal torque and integrated electromyography (lemg) occurs. Maximal torque and
      lemg occurred at 50 degrees for males and 70 degrees for females. This may have
      an effect on the normalization procedure when the quadriceps is studied
      dynamically. The location of maximal myoelectric activity of the quadriceps
      should influence our treatment of patellofemoral disorders when patellar
      biomechanics are considered. J Orthop Sports Phys Ther 1985;6(6):309-314.

PMID- 18802297
TI  - Management of metatarsalgia with foot orthotics.
AB  - Various disorders cause pain in the forefoot. Factors contributing to the
      development of metatarsalgia include: biomechanical alignment, foot biomechanics,
      anatomical structure of the foot and leg, physical activity, and pathological
      disease states. The foot functions to balance and support forward locomotion by
      acting as a mobile adaptor to the ground and as a rigid lever during propulsion
      at the early and late phases of stance. Forefoot pathomechanics results from an
      overload of the anterior support or from an irregular distribution of the
      metatarsal weightbearing load. Orthotic therapy may be provided with insoles made
      from flexible, semiflexible, or rigid materials. The orthotic should be
      individualized in each patient's case. The purpose of treatment is to increase
      weightbearing tolerance by balancing the metatarsal load, assisting proper foot
      biomechanics, and cushioning or protecting the metatarsal heads. J Orthop Sports
      Phys Ther 1985;6(6):324-333.

PMID- 18802298
TI  - The effects of electrical stimulation of normal abductor digiti quinti on
      strength.
AB  - This pilot study investigated the effectiveness of electrical stimulation in
      strengthening normal abductor digiti quinti muscle. The abductor digiti quinti
      (AbDQ) muscle is unique as it may be considered atrophic but otherwise normal
      muscle tissue. Eight healthy subjects participated in this investigation and they
      were randomly divided into two groups. Group A (N = 4) received intermittent
      electrical stimulation with an on-off time ratio of 1:3. Group B (N = 4) received
      intermittent electrical stimulation with an on-off ratio of 1:2. The control
      group C (N = 8) was the nonelectrically stimulated foot of each participant. Each
      subject received 20 treatments of electrical stimulation of 1 hour duration, 5
      days/week for 4 weeks. At the conclusion of the 20 sessions, significant
      improvements (P < 0.0 1) in functional strength were noted in the stimulated
      groups (1 17.9%); the control group improved 9.9%. The data demonstrated that
      electrical stimulation produced increases in the functional strength of the AbDQ.
      J Orthop Sports Phys Ther 1985;6(6):343-346.

PMID- 18802299
TI  - Pollex valgus: orthopaedic management for ulnar instability of the
      metacarpophalangeal joint of the thumb.
AB  - This article describes pollex valgus, the condition of ulnar instability of the
      thumb's rnetacarpophalangeal joint, relevant to the field of physical therapy.
      Following a discussion of the normal anatomy and biomechanics of the
      metacarpophalangeal joint and its component structures, the joint capsule, ulnar
      collateral ligament, accessory ulnar collateral ligament, volar plate, and
      adductor aponeurosis, the author details pollex valgus pathology. Emphasis is
      given to mechanisms of injury and the specific lesions, including ligament sprain
      and rupture, avulsion, joint locking, and the Kaplan and Stener lesions.
      Orthopaedic management of pollex valgus is presented in terms of evaluation, via
      the case history and clinical examination, and treatment, by tape strapping and
      surgical repair. The author concludes with mention of active exercise and joint
      mobilization for the rehabilitation of pollex valgus lesions. J Orthop Sports
      Phys Ther 1986;6(6):334-342.

PMID- 18802300
TI  - Rectus Femoris Muscle Tightness: lntratester Reliability of an Active Knee
      Flexion Test.
AB  - The purpose of this study was to examine the intratester reliability of a test
      designed to measure tightness in the rectus femoris muscle (RFM). The examiner
      measured the angle of knee flexion with a pendulum goniometer after active knee
      flexion with the subject prone and the hips stabilized in extension. The angle of
      knee flexion represents RFM tightness. After an instruction session, the RFM
      tightness of both extremities of 20 men was measured during test and retest
      sessions. The reliability coefficients for test and retest measurements were 0.97
      for the left extremity and 0.97 for the right extremity. The author discusses
      factors that may have contributed to the high reliability, including a well
      defined and easily observed end point of motion, strict hip stabilization, and
      accurate instrument placement. If conducted properly, the test should provide
      clinicians and researchers with an objective and reliable tool for measuring RFM
      tightness. J Orthop Sports Phys Ther 1985;6(5):289-292.

PMID- 18802301
TI  - Case studies: painless reduction of dislocation and fracture of the shoulder
      joint utilizing normal respiration.
AB  - A gentle reduction method using normal respiration was studied, because strong
      traction or compression did not always cause complete reduction in a patient with
      dislocation of the shoulder joint. In two cases with dislocation of the shoulder
      joint complicated by fracture of the diaphysis an sprain fracture of the greater
      tuberculum, complete reduction was obtained by transport of the caput due to the
      patient's own effort with slow normal respiration when his or her anxiety and
      general tenseness subsided. The goal of this method is removal of muscle tone
      interfering with reduction and inducement of muscle tone facilitating reduction.
      J Orthop Sports Phys Ther 1985;6(5):296-298.

PMID- 18802302
TI  - Effects of Gravity-Facilitated Traction on lntervertebral Dimensions of the
      Lumbar Spine*.
AB  - The purpose of this study was to determine the effects of gravity-facilitated
      traction (inversion) on intervertebral dimensions of the lumbar spine. Fifteen
      normal male subjects were fully inverted for a period of 10 minutes. Vertebral
      separation was measured on lateral roentgenograms both pre- and postinversion by
      outlining the margins of the intervertebral bodies both anteriorly and
      posteriorly and the greatest vertical heights of the intervertebral foramina.
      Fine point engineering calipers were used to facilitate measurements. A student t
      test for paired data was used to determine significance of separation between
      lumbar segments, following 10 minutes of inversion. The alpha level was set at
      0.05 for statistical significance. Gravity-facilitated traction produced
      increased separation at all levels measured. Significant increases in total mean
      anterior separation, total mean posterior separation, and total mean
      intervertebral foraminal separation were determined. Mean anterior separation was
      significant at all levels except L3-L4. Mean posterior separation was significant
      at all levels except L1-L2 and L5-S1. Mean intervertebral foraminal separation
      was significant at all levels but L5-S1. If increases in intervertebral
      dimensions play a role in the relief of low back syndrome, then gravity
      facilitated traction may be an effective moda1i;y in the treatment of this
      condition. J Orthop Sports Phys Ther 1985;6(5):281-288.

PMID- 18802303
TI  - Dynamic stabilization of the trunk.
AB  - The lumbopelvic region, because it is the hub of our antigravity weightbearing,
      is the most vulnerable area for spraining and straining tissues. It is also,
      however, the most difficult area to treat because of our inability to completely
      control the healing of these injured tissues. Properly identifying and accurately
      assessing the biomechanics of injury and understanding the basic science of the
      processes of soft tissue healing are critical in order to initiate proper goal
      oriented treatment geared toward regaining normal function of the injured area.
      If normal function is not restored, frequent reinjury and chronic symptoms often
      occur. Because of the background and the knowledge in anatomy, biomechanics, and
      kinesiology the physical therapist is the most qualified to begin a program
      geared toward properly managing this region. Unfortunately, too often it is a
      decrease in overall fitness as well as asymmetrical skeletal forces that
      predispose the lumbopelvic region to injury. That is, it is almost as if these
      people are "accidents waiting to happen. " Attempting to undo that which has been
      progressing for years is a difficult problem for those who treat lumbopelvic
      pain. This paper sets forth one rational approach for effectively stabilizing and
      treating these conditions. J Orthop Sports Phys Ther 1985;6(5):271-277.

PMID- 18802304
TI  - Isokinetic maximal torque power of greek elite soccer players.
AB  - Eighteen elite Greek soccer players (age, 27.8 +/- 3.4 years; height, 176.6 +/-
      5.2 cm; weight, 75.5 +/- 5.2 kg) were tested on the Cybex(R) II apparatus in
      order to determine 1) the maximal muscle power for the lower extremity dominant
      side at angular velocities of 30 degrees /sec, 90 degrees /sec, and 180 degrees
      /sec; 2) the total muscular output and the relative power at 30 degrees /sec; 3)
      the relationship between the muscle power of the agonist and antagonist
      musculature. The absolute maximal muscle power (Nm) at 30 degrees /sec for the
      different joint movements was as follows: Hip Ext = 269 +/- 39; Hip Flex = 179 +/
      29; Hip Add = 160 +/- 17; Hip Abd = 119 +/- 24; Knee Ext = 247 +/- 29; Knee Flex
      = 146 +/- 12; PI. Flex = 120 +/- 22; and Do. Flex = 32 +/- 6. The muscle agonist
      antagonist percent relationship at 30 degrees /sec was found to be: (hip
      flex)/(hip ext) = 66%(hip abd)/(hip add) = 74%(knee flex)/(knee ext) = 60%(dor.
      fle)/(pl. fle) = 28%These findings have significant implications for preseason
      conditioning programs as well as for minimizing the rate of muscle injuries by
      restoring the correct relationship between agonist-antagonist musculature.J
      Orthop Sports Phys Ther 1985;6(5):293-295.

PMID- 18802305
TI  - Geometry of adult rectus abdominis and erector spinae muscles*.
AB  - Mathematical modeling of human joints requires accurate information concerning
      anthropometric parameters such as muscle cross-sectional areas and muscle moment
      arms. The purpose of this study was to calculate the average crosssectional area,
      average volume, and length of the muscle moment arms about the spinal column for
      the rectus abdominis (RA) and the erector spinae (ES) for those portions of the
      muscles that are involved in spinal flexion and extension. Materials for this
      study came from archival computed tomography scans of 28 living subjects. The
      muscle outlines were digitized and the moment arms calculated as a percentage of
      anteroposterior trunk depth. The average cross-sectional area of the RA was 10.5
      cm2, and 31.75 cm2 for the ES. The average volumes for the RA and ES were 356.16
      cm3 and 843.46 cm3, respectively. The muscle moment arm ratio was 0.29 for the
      ES, while the males and females had ratios of 0.50 and 0.40, respectively, for
      the RA. Computed tomography scanning is a method that allows the accurate
      calculation of internal anthropometric parameters that will be of use in
      mathematical modeling. J Orthop Sports Phys Ther 1985;6(5):278-280.

PMID- 18802306
TI  - Muscular strength and flexibility of two female masters swimmers in the eighth
      decade of life*.
AB  - Two female masters swimmers, ages 70 and 71, members of the All-American Masters
      Swim Team were examined for muscular strength and flexibility. Although there is
      a general lack of comparative data, the data which do exist suggest that the
      women examined here had greater muscular strength and flexibility than less
      active women of the same age and were well within the range one would expect for
      normal women who are considerably younger. These findings indicate that regular
      physical training may delay the decline in muscular strength that accompanies
      inactivity during aging and may also offset the age-related decline in
      flexibility. J Orthop Sports Phys Ther 1985;6(4):235-237.

PMID- 18802307
TI  - Shoulder rehabilitation: equipment - - modifications.
AB  - A systematic approach toward weight-training equipment is needed in the physical
      therapy clinic and in establishing guidelines for the home program. Many
      different types of exercise equipment are currently being used. With an
      aggressive patient population, the physical therapist should become familiar with
      the various types of equipment now available in many of the exercise centers. J
      Orthop Sports Phys Ther 1985;6(4):247-253.

PMID- 18802308
TI  - Biomechanics of the shoulder.
AB  - The terminology of engineering has made biomechanics unnecessarily confusing and
      intimidating to many clinicians. Frankel and Burnstein's4 classic text on
      orthopedic biomechanics was so difficult to understand that it was not fully
      appreciated. Fortunately, the gap between mechanical engineers and clinicians has
      been ~losing.'C~o - operation between engineers and clinicians has led to the
      translation of the confusing mathematical properties of biomechanics into
      readable and clinically applicable terms (for example, see Frankel and Nordin5).
      This review will be in keeping with the current trend of basic, clinically
      applicable biomechanics. Specifically, we propose to review the function of the
      shoulder girdle, particularly scapulohumeral control of the arm, describing the
      pertinent mechanical properties. The function of the bones and joints will
      be,related to their structure and forces applied to them. This review should not
      be considered an exhaustive biomechanical analysis of the structures involved.
      References have been provided for that purpose. J Orthop Sports Phys Ther
      1985;6(4):229.334.

PMID- 18802309
TI  - The effects of passive joint mobilization on pain and hypomobility associated
      with adhesive capsulitis of the shoulder.
AB  - The purpose of this investigation was to determine the effects of passive
      mobilization and active exercises in patients with painfully restricted
      shoulders. Twenty patients with painful glenohumeral restrictions were randomly
      placed in one of two groups. The experimental group received mobilization and
      active exercises two to three times per week for 4 weeks. The controls received
      only active exercises. Pain questionnaires were answered and isolated
      glenohumeral mobility measurements were taken initially and at weekly intervals
      during the 4 weeks of treatment. With the exception of internal rotation in the
      control groop, all motions increased significantly from baseline in both groups.
      Passive abduction improved significantly more in the mobilization group than in
      the control group. Pain scores decreased more in the mobilization group; however,
      the difference between the groups was not significant. The results suggest that
      joint mobilization and exercises are clinically effective in the treatment of
      painfully stiff shoulders. J Orthop Sports Phys Ther 1985;6(4):238-246.

PMID- 18802310
TI  - Case studies: the suprascapular nerve and shoulder dysfunction*.
AB  - Since the initial symptoms usually include pain, an entrapment of the
      suprascapsular nerve may be mistaken for a shoulder disorder of musculoskeletal
      origin. However, upon examination, glenohumeral weakness during abduction,
      flexion, and external rotation with concomitant atrophy of the spinati muscles
      may be evident. Documentation is made with electroneuromyographic testing.
      Stretching the nerve is contraindicated; therefore, patients should be instructed
      to avoid activities which require scapular protraction and glenohumeral
      horizontal adduction. Furthermore, as the nerve heals, exercises to strengthen
      the weak muscles should be of benefit. J Orthop Sports Phys Ther 1985;6(4):254
      258.

PMID- 18802311
TI  - Impact of subvalvular procedure for ischemic mitral regurgitation on leaflet
      configuration, mobility, and recurrence.
AB  - BACKGROUND: Procedures on the subvalvular apparatus are an etiology-based
      treatment for ischemic mitral regurgitation (IMR). METHODS AND RESULTS: Fifty
      nine patients with IMR were divided into 3 groups: mitral annuloplasty (MAP) (M
      group, n=27), MAP+left ventricular reconstruction (LVR) (LV group, n=18), and
      MAP+LVR+subvalvular procedure (S group, n=14). Tenting height and area, angle
      between the annular line and the line connecting leaflet base to the bending- or
      tip-point of either the anterior or posterior leaflet, and leaflet mobility were
      measured echocardiographically preoperatively and at immediate- and mid-term
      postoperative follow-up. The angles at the bending-point of the anterior leaflet
      in mid-systole remained greater than those at its tip-point in the M and LV
      groups, but became significantly smaller postoperatively only in the S group
      (p<0.05). Postoperative leaflet mobility at the bending-point in the S group
      became significantly greater than in the other groups (p<0.01). The grade of MR,
      after significant reduction by the procedure, increased again in the M and LV
      groups, but remained almost unchanged in the S group. CONCLUSION: Subvalvular
      procedures improved the configuration and mobility of the anterior leaflet, and
      can be expected to reduce the recurrence of IMR.

PMID- 18802312
TI  - Long-term results of left ventricular reconstructive surgery in patients with
      ischemic dilated cardiomyopathy: a multicenter study.
AB  - BACKGROUND: Left ventricular restoration (LVR) is increasingly used for treatment
      of chronic heart failure following myocardial infarction. The present multi
      institutional retrospective study analyzed the long-term efficacy and limitations
      of LVR. METHODS AND RESULTS: Seventy-two (58 males, mean age 62+/-10) patients
      who underwent LVR between January 1999 and June 2007 were included.
      Preoperatively, 50 (68.5%) were in New York Heart Association (NYHA) functional
      class III or IV. Mean left ventricular end-diastolic and end-systolic volume
      indexes were 145+/-43 ml/m(2) and 111+/-40 ml/m(2), respectively, and ejection
      fraction was 25+/-7.4%. Other concomitant operative procedures included coronary
      artery bypass grafting in 55 (76.4%), and mitral valve procedures in 38 (52.8%).
      Thirty-day mortality was 2.8%. Actuarial survival at 1, 3, and 5 years was 95.3%,
      80.45 and 71.0% respectively. Mean ejection fraction significantly improved to
      39+/-11%, and left ventricular volumes were significantly reduced in the early
      postoperative period. During a mean of 3.3+/-2.4 years of follow up, these
      improvements were still significant in the late period. Of the survivors, 90%
      were in NYHA functional class I or II. CONCLUSION: LVR can be performed with a
      low operative mortality and provide satisfactory long-term survival by restoring
      the dilated left ventricle and improving systolic function.

PMID- 18802313
TI  - Aortic arch calcification and arterial stiffness are independent factors for
      diastolic left ventricular dysfunction in chronic hemodialysis patients.
AB  - BACKGROUND: Because cardiovascular disease is the major cause of death in
      dialysis patients, the correlation between diastolic left ventricular (LV)
      dysfunction and arterial sclerosis, including thoracic aortic calcification, was
      studied in chronic hemodialysis (HD) patients. METHODS AND RESULTS: The enrolled
      study subjects were 142 (73 men, 69 women) maintenance HD patients. Aortic arch
      calcification volume (AoACV) was measured by MDCT scan, arterial stiffness was
      estimated by brachial-ankle pulse wave velocity (PWV) and diastolic LV function
      was estimated as E/E' by tissue Doppler imaging with cardiac ultrasonography.
      E/E' correlated significantly with systolic blood pressure (r=0.29, p=0.037), age
      (r=0.19, p=0.02), LV mass index (r=0.18, p=0.036), dialysis vintage (r=0.19,
      p=0.037), AoACV (r=0.37, p<0.0001) and PWV (r=0.33, p=0.0002). Multiple
      regression analysis indicated that AoACV (beta=0.26, p=0.005) and PWV (beta=0.22,
      p=0.03) were independent determinants of E/E'. CONCLUSION: Diastolic LV
      dysfunction may be induced by increased vascular calcification and reduced
      arterial stiffness in chronic HD patients.

PMID- 18802314
TI  - Serum L-homoarginine concentration is elevated during normal pregnancy and is
      related to flow-mediated vasodilatation.
AB  - BACKGROUND: Normal pregnancy is associated with enhanced vasodilatation because
      of the increased nitric oxide (NO) production. Because L-homoarginine can act as
      a substrate for NO production, concentrations of L-homoarginine in normal
      pregnancy were assessed in the present study to test whether L-homoarginine is
      associated with endothelial function. METHODS AND RESULTS: Healthy non-pregnant
      (n=61) and pregnant women (n=58) were studied in a cross-sectional study. L
      homoarginine, L-arginine, asymmetric dimethylarginine and symmetric
      dimethylarginine concentrations were determined simultaneously by high
      performance liquid chromatography. Endothelium-dependent brachial artery flow
      mediated dilation (FMD) was measured by ultrasound. The serum L-homoarginine
      concentration was significantly higher during the second and the third trimesters
      compared with the levels in the non-pregnant women (4.8+/-1.7 and 5.3+/-1.5 vs
      2.7+/-1.0 micromol/L, p<0.001, respectively). In line with this, FMD increased in
      response to pregnancy (p<0.05). Three months after delivery, the L-homoarginine
      concentrations and FMD were comparable to those recorded in the non-pregnant
      females. The concentration of L-homoarginine correlated significantly with
      gestational age (r=0.426, p=0.001) and brachial artery diameter and FMD (r=0.362,
      p=0.006 and r=0.306, p=0.022, respectively) in pregnancy. CONCLUSIONS: L
      homoarginine appears to be increased during the second and third trimesters of
      pregnancy and may contribute to the enhanced endothelial function in normal
      pregnancies.

PMID- 18802315
TI  - Relationship of cardio-ankle vascular index (CAVI) to carotid and coronary
      arteriosclerosis.
AB  - BACKGROUND: The cardio-ankle vascular index (CAVI) has been recently reported as
      a new index of aortic stiffness, which is less influenced by blood pressure than
      pulse wave velocity (PWV). The present study investigated the relationship
      between the levels of CAVI and carotid and coronary arteriosclerosis. METHODS AND
      RESULTS: The 443 consecutive patients who underwent CAVI, carotid sonography, and
      coronary angiography in hospital were examined. Intima-media thickness (IMT) and
      carotid plaque were evaluated by ultrasonography. The severity of coronary artery
      disease (CAD) was evaluated by coronary angiography and the subjects were divided
      into 4 groups (0, no significant organic stenosis: 1, 1-vessel disease: 2, 2
      vessel disease: 3, 3-vessel disease). Univariate analyses showed that both CAVI
      and brachial-ankle PWV (baPWV) were associated with IMT and the presence of
      carotid plaque. Multiple stepwise regression analyses revealed that CAVI
      (p=0.0427), but not baPWV, was associated with the IMT. Both CAVI (p<0.0001) and
      baPWV (p=0.0140) were significantly associated with the severity of CAD. Multiple
      logistic analyses revealed that CAVI (p=0.0342), but not baPWV (p=0.8027), was
      associated with the presence of multivessel disease. CONCLUSION: High CAVI
      implies progression of carotid and coronary arteriosclerosis. CAVI may be more
      closely linked with arteriosclerosis than baPWV.

PMID- 18802316
TI  - Isolated undersized mitral annuloplasty for functional mitral regurgitation in
      non-ischemic dilated cardiomyopathy: reconsideration of the relationship between
      preoperative coaptation depth and persistent mitral regurgitation.
AB  - BACKGROUND: A preoperative coaptation depth (CD) >or=11 mm is apparently a
      predictive factor for persistent mitral regurgitation (MR) after undersized
      mitral annuloplasty for functional MR. The results of studies of isolated
      undersized mitral annuloplasty in non-ischemic dilated cardiomyopathy (DCM) are
      reported, including the relationship between the preoperative CD and recurrent
      MR. METHODS AND RESULTS: Six patients (mean age, 61 years) with severe functional
      MR in non-ischemic DCM underwent isolated undersized mitral annuloplasty. There
      were no hospital deaths. At intermediate follow-up of 2.2+/-1.9 years, New York
      Heart Association functional class improved significantly from 3.3+/-0.5 before
      surgery to 2.2+/-0.4 after surgery (p=0.0016). At a mean echocardiographic follow
      up of 1.9+/-1.7 years, MR grade improved significantly from 4.0+/-0.0 before
      surgery to 1.0+/-0.6 after surgery (p<0.001). In 4 of 5 patients with a
      preoperative CD >or=11 mm, functional MR improved to mild or less than mild after
      surgery. CONCLUSIONS: Isolated undersized mitral annuloplasty improved clinical
      symptoms and functional MR in non-ischemic DCM. These results suggest that
      preoperative CD >or=11 mm does not always predict recurrent MR after isolated
      undersized mitral annuloplasty for functional MR in cases of non-ischemic DCM.

PMID- 18802317
TI  - Presence of previously undescribed bacterial taxa in non-axenic Chlorella
      cultures.
AB  - We determined the bacterial community profile in non-axenic cultures of Chlorella
      (Chlorophyceae, Chlorophyta) isolated from soil. The bacterial composition at the
      phylum level was different from that of whole soil bacteria, but it was similar
      to that reported for non-axenic cultures of marine microalgae such as diatoms
      (Bacillariophyceae, Heterokontophyta). Expected novel bacteria, i.e. those which
      do not have close relatives among described species, were maintained in the
      cultures, and these bacteria were chiefly composed of members of the phylum
      Bacteroidetes. They may have been 'as-yet-uncultured' but in practice
      unintentionally been cultured in microalgal cultures. They could serve as good
      bioresources in various fields of biological and ecological studies.

PMID- 18802318
TI  - Air-borne microbial contamination of surfaces in a UK dental clinic.
AB  - Little is known about the number, type, or antibiotic resistance profiles, of air
      borne microbes present in hospital settings yet such information is important in
      designing effective measures to reduce cross-infection. In this study settle
      plates were used to identify and quantify the air-borne microbes present in a
      dental clinic. All isolates were identified to species level using partial 16S
      ribosomal RNA gene sequencing and their susceptibility to ampicillin,
      chloramphenicol, erythromycin, gentamicin, penicillin, tetracycline or vancomycin
      was performed. The mean numbers of viable bacteria detected for each sampling
      occasion during periods of clinical activity and in the absence of such activity
      were 21.9 x 10(2 )cfu/m2/h and 2.3 x 10(2 )cfu/m2/h respectively. One hundred
      ninety-three distinct colony morphotypes, comprising 73 species, were isolated
      during the study and 48% of these were resistant to at least one antibiotic. The
      mean numbers of different morphotypes detected per sampling occasion were 14.3
      and 5 during periods of clinical activity and inactivity respectively.
      Propionibacterium acnes, Micrococcus luteus and Staphylococcus epidermidis were
      frequently isolated regardless of whether any clinical activities were taking
      place. These findings highlight the importance of preventing surfaces from
      becoming reservoirs of antibiotic-resistant bacteria and thereby contributing to
      cross-infection in the dental clinic.

PMID- 18802319
TI  - Microbial community in the rhizosphere of young maize seedlings is susceptible to
      the impact of introduced pseudomonads as indicated by FAME analysis.
AB  - Two species of Pseudomonas (i.e. P. chlororaphis or P. putida) derived from a
      maize rhizosphere were studied for their impact on the structure of the microbial
      community in the rhizosphere of young maize seedlings after inoculation. The
      culturable bacteria and total microbial communities were analyzed based on
      profiles of whole-cell fatty acid methyl esters (MIDI-FAME). The introduction of
      Pseudomonas species resulted in the shift from the Gram-positive dominated
      culturable community in the rhizosphere of uninoculated maize to more Gram
      negative populations in the rhizospheres of the inoculated plants. For the total
      rhizosphere communities, 43, 47 and 42 FAMEs were detected in the uninoculated
      maize and the samples inoculated with P. chlororaphis or P. putida, respectively.
      In contrast to the culturable communities, low concentrations of marker FAMEs for
      Gram-positives (i15:0, a15:0, i16:0) were found in the profiles of the total
      rhizosphere communities. The maize inoculations resulted in an enrichment of some
      Gram-negative isolates; however, Gram-positive bacteria, Cytophaga/Flavobacterium
      and saprophytic fungi were found in the uninoculated rhizosphere.

PMID- 18802320
TI  - Gluconobacter sphaericus (Ameyama 1975) comb. nov., a brown pigment-producing
      acetic acid bacterium in the Alphaproteobacteria.
AB  - Strain NBRC 12467T was examined genetically, phylogenetically, phenotypically,
      and chemotaxonomically. The DNA G+C content of the strain was 59.5 mol%. The
      strain represented low levels of DNA-DNA hybridization of 49-9% to the type
      strains of eight Gluconobacter species. The strain formed a cluster along with
      the type strains of G. albidus and G. kondonii in phylogenetic trees based on 16S
      rRNA gene sequences. In a phylogenetic tree based on 16S-23S rRNA gene ITS
      sequences, however, the strain formed an independent cluster from the type
      strains of the eight Gluconobacter species. Such phylogenetic relationships were
      supported by the calculated pair-wise 16S rRNA gene and 16S-23S rRNA gene ITS
      sequence similarities. The strain was distinguished from the type strains of the
      eight Gluconobacter species by 16S-23S rRNA gene ITS restriction analysis using
      five restriction endonucleases. The strain produced a water-soluble brown pigment
      and 2,5-diketo-D-gluconate from D-glucose, differing from the type strains of the
      eight Gluconobacter species, and acid from meso-erythritol very weakly, differing
      from the type strains of the remaining seven Gluconobacter species except for the
      type strain of G. roseus, but not from maltose, differing from the type strain of
      G. oxydans, and had Q-10. For the strain, which was once classified as G. oxydans
      subsp. sphaericus, Gluconobacter sphaericus (Ameyama 1975) comb. nov. is
      proposed. The type strain is NBRC 12467T, which is also deposited as BCC 14448T.

PMID- 18802321
TI  - Influence of pH conditions on the viability of Saccharomyces boulardii yeast.
AB  - Saccharomyces boulardii is a probiotic with proven health benefits. However its
      survival is challenged by gastrointestinal transit, and a ratio between 1 and 3%
      of living yeast is recovered in the feces after oral administration. The aim of
      the study was to determine to what extent the yeast was sensitive to
      gastrointestinal pH conditions. Therefore we explored the survival of different
      concentrations of S. boulardii in conditions mimicking the stomach pH (pH 1.1 0.1
      N HCl) and the intestinal pH (pH 6.8 phosphate buffer) in vitro. The probiotic
      being commercialized as a freeze-dried powder obtained from an aqueous
      suspension, both forms were evaluated. In phosphate buffer pH 6.8, the viability
      remained stable for both forms of S. boulardii for 6 h. In HCl pH 1.1, viability
      of both forms (200 mg L(-1)) significantly decreased from 5 min. Observation
      under scanning/transmission electron microscopy showed morphological damages and
      rupture of the yeast wall. Threshold value from which S. boulardii viability was
      unaltered was pH 4. At the highest concentration of 200 g L(-1), the initial pH
      value of 1.1 rose to 3.2, exerting a protective effect. In conclusion, although
      the yeast in aqueous suspension was less sensitive than the freeze-dried yeast to
      acidic conditions, a gastric protection for improvement of oral bioavailability
      of viable S. boulardii appears necessary.

PMID- 18802322
TI  - Polyamine distribution profiles of new members of the phylum Bacteroidetes.

PMID- 18802323
TI  - The growth and recovery of an exopolysaccharide-producing Lactobacillus rhamnosus
      culture on growth media containing apple juice or molasses.

PMID- 18802324
TI  - ERp29 is a radiation-responsive gene in IEC-6 cell.
AB  - ERp29 is a resident protein of the endoplasmic reticulum (ER) lumen, which is
      thought to be involved in the folding of secretory proteins. In our previous
      work, it was found that, when treated with ionizing radiation (IR), the ERp29
      expression was increased in mouse intestinal epithelia and cultured IEC-6 cells,
      which suggested that ERp29 might be a radiation-induced gene. The current work is
      to confirm the induction of ERp29 by IR and to analyze its role in irradiated IEC
      6 cells. Our results showed that ERp29 expression was elevated by IR in IEC-6
      cells at mRNA and protein levels in a time-dependent manner. IEC-6 cells with
      different exogenous ERp29 expression were obtained by transfection with sense and
      antisense expression vectors of ERp29 coding region. As ERp29 expression was
      inhibited, these cells exhibited more serious radiation injury and more
      sensitivity to IR-induced apoptosis. To further elucidate the induction of ERp29,
      we analyzed the XBP1 expression after IR. Results showed that the spliced form of
      XBP1 mRNA rapidly reached a peak at 3 hours after irradiation, which indicated
      that UPR sensor was involved in radiation and might be a reason to induce ERp29
      expression. Our results demonstrate that ERp29 is a radiation associated protein
      and plays an important role in protecting cells from IR.

PMID- 18802325
TI  - Non-enzymatic glycation of human fibrillin-1.
AB  - Non-enzymatic glycation of proteins is one of the key mechanisms in the
      pathogenesis of diabetic complications and may be significant in the age-related
      changes of tissues. We isolated and investigated the in vitro glycation of human
      aortic fibrillin-1. Fibrillin-1 was prepared from thoracic aortas of 9 accident
      victims distributed in three age groups. The purity of isolated fibrillin-1 was
      proved. It was glycated by incubating with different glucose concentrations in
      0.2 M phosphate buffer, pH 7.4, for 30 days, at 37 degrees C. The degree of early
      products of glycation was measured by two colorimetric methods, i.e. nitroblue
      tetrazolium and 2-thiobarbituric acid. Advanced glycation end products (AGEs)
      were determined by fluorescence measurement. The highest level of early products
      of glycation was found on day 2 after the beginning of incubation for the
      fibrillin-1 isolated from the youngest group. Fluorescence in the age groups, as
      an index of advanced glycation, consistently increased between days 6 and 24. The
      fibrillin-1 isolated from the youngest group had the highest capacity to form
      fructosamine and AGEs under glycation in vitro. The capacity of glycation of the
      'oldest' fibrillin did not increase significantly during the incubation.
      Investigation of the properties of glycated fibrillin-1 will help to understand
      the importance of this long-lived protein to age-related changes in tissues and
      for diabetic complications.

PMID- 18802326
TI  - Evaluation of genetic association and expression reduction of TRPC1 in the
      development of diabetic nephropathy.
AB  - BACKGROUND/AIMS: The TRPC1 gene on chromosome 3q22-24 resides within the linkage
      region for diabetic nephropathy (DN) in type 1 (T1D) and type 2 diabetes mellitus
      (T2D). A recent study has demonstrated that TRPC1 expression is reduced in the
      kidney of diabetic ZDF- and STZ-treated rats. The present study aimed to evaluate
      the genetic and functional role of TRPC1 in the development of DN. METHODS:
      Genetic association study was performed with two independent cohorts, including
      1,177 T1D European Americans with or without DN from GoKinD population and 850
      African-American subjects with T2D-associated end-stage renal disease (ESRD), or
      with hypertensive (non-diabetic) ESRD, and nondiabetic controls. Seven tag SNP
      markers derived from HapMap data (phase II) were genotyped. TRPC1 gene expression
      was examined using real time RT-PCR. RESULTS: No significant association of TRPC1
      DNA polymorphisms with DN or ERSD was found in GoKinD and African-American
      populations. TRPC1 gene mRNA expression in kidney was found to be trendily
      reduced in 12-week and significantly in 26-week-old db/db mice. CONCLUSIONS:
      TRPC1 genetic polymorphism may not fundamentally contribute to the development of
      DN, while reduction of the gene expression in kidney may be a late phenomenon of
      DN as seen in diabetic animal models.

PMID- 18802327
TI  - Normalizing NADPH oxidase contributes to attenuating diabetic nephropathy by the
      dual endothelin receptor antagonist CPU0213 in rats.
AB  - BACKGROUND/AIMS: NADPH oxidase(NOX) is the main source of reactive oxygen species
      (ROS) in diabetic nephropathy (DN). Activation of NOX could be mediated via
      endothelin A (ET(A)R) and B receptors (ET(B)R) of the endothelin (ET) system.
      Thus, CPU0213, a dual ET receptor antagonist, was expected to attenuate DN by
      suppressing NOX. METHODS: Diabetes was produced in male Sprague-Dawley rats 8
      weeks after a single injection of streptozotocin (STZ), and treatment with
      CPU0213 was initiated in the last 4 weeks. Rat mesangial cells (MCs) were
      incubated with 30 mM glucose for 48 h supplemented with CPU0213 or the NOX
      inhibitors apocynin and diphenyleneiodonium. RESULTS: After 8 weeks of
      hyperglycemia, abnormal renal function was associated with oxidative stress and
      an increased renal weight index in STZ-treated rats. Additionally, upregulation
      of NOX subunits and the ET system was found in diabetic rats and MCs treated with
      30 mM glucose and suppressed by CPU0213 or NOX inhibitors. Except for blood
      glucose, CPU0213 markedly suppressed these abnormalities in DN. CONCLUSION:
      Upregulation of NOX is associated with upregulation of the ET pathway in the
      pathology of DN. The dual ET receptor antagonist (ET(A)R and ET(B)R) CPU0213
      effectively normalized renal function in DN by suppressing NOX.

PMID- 18802328
TI  - Elevated osteoprotegerin levels predict cardiovascular events in new hemodialysis
      patients.
AB  - BACKGROUND: Patients on hemodialysis (HD) frequently experience cardiovascular
      events associated with vascular calcification. We investigated the involvement of
      osteoprotegerin (OPG), an inhibitor of vascular calcification, in the incidence
      of cardiovascular events and mortality among new HD patients. METHODS: We
      conducted a prospective cohort study of the association of serum OPG levels with
      morbidity and mortality in subjects who became new HD patients between June 2000
      and May 2006. RESULTS: A total of 99 patients (age 58.9 +/- 14.6 years, 65 male,
      34 female) were prospectively followed up for 41.5 +/- 20.2 months. During this
      period, 27 patients developed cardiovascular events and 12 died of causes related
      to cardiovascular disease. When divided into 2 groups according to OPG levels,
      the high OPG group showed a higher prevalence of cardiovascular morbidity and
      mortality compared with the low OPG group. Cox's proportional hazards analysis
      associated the new onset of cardiovascular events with the high OPG group (HR
      2.88, 95% CI 1.09-7.62, p = 0.033). Furthermore, the high OPG group at the start
      of HD was significantly associated with older age, male gender and a high aortic
      calcification index. CONCLUSIONS: Elevated levels of serum OPG in new HD patients
      may predict subsequent cardiovascular events.

PMID- 18802329
TI  - Urinary iodine in 24 h is associated with natriuresis and is better reflected by
      an afternoon sample.
AB  - AIMS: We aimed to assess the extent of variability in urinary iodine (UI) within
      a day, to determine the period of the day when UI was better associated with the
      UI in 24 h, and to study the relationship between UI and urinary sodium. METHODS:
      This cross-sectional study included 60 volunteers. Four urine samples were
      collected from each participant (A: from breakfast to lunch; B: from lunch to
      dinner; C: from dinner to bedtime, and D: from bedtime to breakfast) and were
      compared with the 24-hour sample (calculated from samples A-D ). UI, creatinine
      and Na(+) levels were measured in the partial samples and in the 24-hour sample.
      RESULTS: The content of iodine and sodium in urine varied during the day (p <
      0.001). The UI concentration from lunch to dinner was closest to the 24-hour UI
      concentration using the method of Bland and Altman. There were correlations
      between the UI content in the different periods of the day and in 24 h: A (r =
      0.54; p < 0.000), B (r = 0.78; p < 0.000), C (r = 0.37; p = 0.004) and D (r =
      0.77; p < 0.000). UI and urinary sodium content were strongly correlated in all
      periods of the day (samples A and B: r = 0.69, p < 0.000; sample C: r = 0.85, p <
      0.000, and sample D: r = 0.78, p < 0.000). CONCLUSIONS: There was a within-day
      variation in UI content, which was strongly associated with urinary sodium
      content. Iodine concentration in the afternoon urine sample better reflected the
      24-hour UI concentration. Therefore, urine collected in the afternoon is probably
      the best to evaluate iodine sufficiency in subjects with similar dietary habits.

PMID- 18802330
TI  - Fatty acid profile of human milk of Portuguese lactating women: prospective study
      from the 1st to the 16th week of lactation.
AB  - BACKGROUND/AIMS: Fatty acid (FA) composition varies over the course of the day
      and during lactation. The aim of this study was to evaluate FA composition and
      its compositional stability in human milk, from day 7 to week 16 of lactation.
      METHODS: Human milk was collected from all feedings over 24 h at day 7 and weeks
      4, 8, 12 and 16 of lactation in 31 lactating women. FAs were analyzed through gas
      chromatography. Comparisons were made with analysis of variance. RESULTS: Total
      monounsaturated FAs decreased from 33.04 +/- 2.58% wt/wt at day 7 to 31.48 +/-
      3.32% wt/wt at week 16 of lactation, much at the expenses of the decrease in the
      major monounsaturated FA found in human milk, oleic acid. Main polyunsaturated
      FAs n-6 and n-3 showed fluctuations from day 7 up to week 16 of lactation, but
      with no statistical significance. Arachidonic acid significantly decreased from
      transitional to mature milk. CONCLUSIONS: The FA profile obtained throughout the
      study time points presented very low levels of oleic acid and very high linoleic
      acid/alpha-linoleic acid ratios which reflect recent changes in Portuguese
      women's food patterns. Despite this, the arachidonic acid/docosahexaenoic acid
      ratio [corrected] remained constant during the study, suggesting a protective
      metabolic mechanism.

PMID- 18802331
TI  - Th17 and treg cells innovate the TH1/TH2 concept and allergy research.
AB  - Allergic reactions are caused by harmless allergens, which are recognized by the
      specific immune system. Allergen-specific T cells are assumed to play a key role
      in the sensitization phase and in immunological memory. Current immunological
      concepts suggest that asymptomatic T-cell memory cells also exist, tagging the
      allergen as harmless and preventing an inappropriate response and thus allergic
      symptoms. Proinflammatory T cells mediate allergic inflammation by exceeding the
      induction of IgE and competing with other T-cell subsets. Therefore, molecular
      mechanisms leading to pro- or anti-inflammatory T-cell memory cells appear as the
      key mechanism in allergy.

PMID- 18802332
TI  - Regulatory T cells and antigen-specific tolerance.
AB  - Foxp3-expressing regulatory T cells (Tregs) have an essential function of
      preventing autoimmune disease in man and mouse. Foxp3 binds to forkhead motifs of
      about 1,100 genes and the strength of binding increases upon PMA/ionomycin
      stimulation. In Foxp3-expressing T-cell hybridomas, Foxp3 promoter binding does
      not lead to activation or suppression of genes which becomes only visible after T
      cell activation. These findings are in line with observations by others that
      Foxp3 exerts important functions through association with Tcell receptor (TCR)
      dependent transcription factors in a DNAbinding complex. Tregs can be generated
      when developing T cells encounter TCR agonist ligands in the thymus. This pro -
      cess requires costimulatory signals. In contrast, extra thymic conversion of
      naive T cells into Tregs is inhibited by costimulation. In fact, DC-derived
      retinoic acid (RA) helps the conversion process by counteracting the negative
      impact of costimulation. Since AP-1 is produced after costimulation and appears
      to interfere with Foxp3-NFAT transcription complexes, it is of interest to note
      that RA interferes with AP-1-dependent transcription. Thus, RA may interfere with
      the negative impact of costimulation on Treg conversion by interfering with the
      generation and/or function of AP-1.

PMID- 18802333
TI  - Molecular mechanisms of regulatory T-cell development.
AB  - CD4+CD25+ natural regulatory T (nTR) lymphocytes represent a separate, thymus
      derived T-cell lineage that is essential to the maintenance of immunological
      tolerance in the host. Their deficiency or dysfunction has been implicated in the
      pathogenesis of allergic and autoimmune diseases. The discovery of Foxp3 as a
      transcription factor essential to the differentiation of CD4+CD25+ TR cells
      ushered detailed studies into the molecular mechanisms of TR cell development,
      peripheral homeostasis and effector functions. A second group of induced TR (iTR)
      cells can be derived de novo from conventional CD4+ T cells upon antigenic
      stimulation in the presence of TGF-Beta and IL-2. This process is especially
      active at the mucosal interface in the gut, and plays a critical role in the
      induction of oral tolerance to allergens and other antigens. Augmentation of TR
      cells by immunotherapy and pharmacologic agents is a promising strategy in the
      treatment of allergic and autoimmune diseases.

PMID- 18802334
TI  - Interaction of regulatory T cells with antigen-presenting cells in health and
      disease.
AB  - Among antigen-presenting cells (APCs), dendritic cells as well as monocytes
      acquire immunostimulatory capacity only after appropriate maturation. Therefore,
      blockade of the maturation/activation results in a steady state or alternatively
      activated phenotype, which induces tolerance rather than immunity. Functional
      analyses revealed recently that steady-state dendritic cells and alternatively
      activated macrophages, respectively, actively induce regulatory T cells (Tregs)
      in the periphery of the body. Thus, production of Tregs does not rely exclusively
      on thymic development. Vice versa, Tregs respond to APCs by several means. Recent
      lines of evidence indicate that Tregs prevent terminal differentiation of
      subpopulations of APCs or lead to upregulation of surface expression of
      immunosuppressive molecules. Thus, Tregs foster an environment that further
      promotes their development. In conclusion, the mutual interaction of Tregs and
      APCs enables Tregs to sustain their immunosuppressive function(s), which in
      healthy individuals may be crucial for the maintenance of peripheral tolerance.
      Since macrophages bridge the innate and the acquired immune system, Tregs are
      able to gain influence on the innate immune system by interacting with
      macrophages beyond the mere interaction with effector T cells.

PMID- 18802335
TI  - Mucosal regulatory T cells in airway hyperresponsiveness.
AB  - Interest in regulatory T cells (Treg) and their role in immune regulation has
      grown almost exponentially over the last 10 years, though the notion of a
      suppressive population of T cells has been in existence since the early 1970s.
      Recent reports have highlighted the potential role of populations of Treg in
      control of T-cell-mediated inflammation in tissues, including the lung. In
      particular, there is now evidence to suggest that Treg form a fundamental part of
      the regulatory axis operating within the respiratory mucosa and that the number
      of Treg recruited to the airways may be crucial for the inhibition of airways
      hyperresponsiveness associated with exacerbations of asthma. A discussion of
      these concepts is the focus of this chapter.

PMID- 18802336
TI  - Natural killer cells in allergic inflammation.
AB  - Natural killer (NK) cells are large granular lymphocytes of the innate immune
      system that exert a potent function against infected and tumor cells. Although NK
      cells were originally defined by their capacity to lyse target cells and produce
      interferon-gamma without prior activation, recent studies showed that NK cells
      also display a potent regulatory function. They are activated or inhibited
      through the ligation of germline-encoded receptors and are involved in mediating
      cytotoxicity, producing cytokines and providing costimulation to cells of the
      adaptive immune system. NK cells play important roles in viral infections,
      autoimmunity, pregnancy, cancer and bone marrow transplantation, but little is
      known about the role of NK cells in allergy. Recent developments in the
      understanding of the role of human NK cells in allergy are overviewed.

PMID- 18802337
TI  - Mast cells and mast cell-derived factors in the regulation of allergic
      sensitization.
AB  - Mast cells have been mainly regarded as effector cells in IgE-dependent mucosal
      immunity, including the host response to helminthic parasites but also the
      formidable and sometimes fatal anaphylactic reactions to inhaled or ingested
      allergens. Work performed mostly within the last decade revealed novel functions
      for mast cells as critical initiators of fast inflammatory reactions upon IgE
      independent activation. Thus, their role as a sentinel in innate immunity also
      suggests that mast cells are able to bridge innate and adaptive immunity. Herein,
      we will summarize the accumulating evidence that mast cells are also able to
      promote and to modulate the development of adaptive immune reactions with
      emphasis on their role in allergic sensitization in skin and lung. Based on
      murine data published so far, it is becoming apparent that mast cells and their
      mediators are of critical relevance for allergen sensitization under conditions
      which more closely resemble physiological contact with allergens. Yet, the
      function of mast cells can sometimes be bypassed using vigorous sensitization
      protocols, a finding which should be taken into account when animal models for
      complex human diseases are investigated.

PMID- 18802338
TI  - Regulatory effects of histamine and histamine receptor expression in human
      allergic immune responses.
AB  - Histamine influences several immune/inflammatory and effector functions in
      addition to its dominant role in type I hypersensitivity reactions. Histamine can
      selectively recruit the major effector cells into tissue sites and affect their
      maturation, activation, polarization, and other functions leading to chronic
      inflammation. Histamine also regulates monocytes, dendritic cells, T cells and B
      cells, as well as related antibody isotype responses. The diverse effects of
      histamine on immune regulation appear to be due to differential expression and
      regulation of four types of histamine receptors and their distinct intracellular
      signals. In addition, differences in affinities of these receptors for histamine
      are highly decisive for the biological effects of histamine and drugs that target
      histamine receptors.

PMID- 18802339
TI  - T-cell regulation in asthmatic diseases.
AB  - Effector and regulatory T cells (Tregs) play a fundamental role in the airways in
      allergic asthma. Here, the role of T cells in the immunopathogenesis of human
      asthma as well as in animal models of allergic airway inflammation is reviewed.
      Recent data have shown that Th2 and Th17 effector T cells augment experimental
      airway inflammation, while Tregs have an important anti-inflammatory function.
      The local induction of Th2 cells is critically dependent on the balance between
      the transcription factors T-bet and GATA-3, while Th17 and Tregs require the
      transcription factors ROR-gammat and Foxp3, respectively. Cytokine signaling
      controls the development and activation of all the above T-cell subsets. For
      instance, local blockade of the membrane-bound interleukin (IL)-6R results in
      induction of lung CD4+CD25+ Foxp3+Tregs producing TGF-Beta and IL-10. In humans,
      it has been suggested that asthmatic patients have increased Th2 but decreased
      Tregs, however the role of Th17 cells in allergic asthma remains to be
      elucidated. However, the currently available data suggest that allergic asthma is
      a multifaceted disease that is actively controlled by T lymphocytes. A better
      understanding of effector and Treg activation will most likely lead to novel
      treatment strategies in the near future.

PMID- 18802340
TI  - Immune regulatory mechanisms in allergic contact dermatitis and contact
      sensitization.
AB  - Contact allergy is a very common disease due to an uncontrolled immune response
      to chemically reactive small molecular compounds penetrating the skin. The
      reaction is mostly sustained by specific CD8+and CD4+type 1 T lymphocytes, which
      are recruited at the site of chemical challenge thanks to the expression of
      specific homing and chemokine receptors. Evidence exists that specialized subsets
      of T lymphocytes with regulatory function modulate immune responses to haptens by
      preventing the occurrence of the hypersensitivity reactions in non-allergic
      individuals exposed to the sensitizer. In addition, the magnitude of the
      inflammatory reaction in allergic individuals is also tightly regulated not only
      by the exhaustion/ apoptosis of effector T cells at the site of chemical
      challenge, but also by the intervention of T-regulatory cells. Most of the T
      regulatory cells involved in this process belong to the CD4+ subset, such as the
      IL-10-producing T cells, namely Tregulatory cells 1, and the CD4+CD25+T
      regulatory lymphocytes. In addition, reports suggest the existence of Treg
      activity among the CD8+ subpopulation. The currently held view is that contact
      allergies are the consequences of the exaggerated expansion of specific CD8+
      effector T lymphocytes due to an impaired development of efficient regulatory T
      cells.

PMID- 18802341
TI  - Regulatory role of T lymphocytes in atopic dermatitis.
AB  - Eczema does not occur in the absence of T cells. Here we provide an overview on
      the regulatory impact which T cells have on the establishment and maintenance of
      atopic dermatitis. Particularly, we outline the role of different T-helper cell
      subsets (i.e. Th-1, Th-2, T-regulatory and Th-17 cells) and their distinct
      influence on the cutaneous inflammatory reaction at different stages of the
      disease. Eczema is characterized by epidermal inflammation and thus T-cell/ker -
      atinocyte interactions are of particular relevance in this condition. Alterations
      in innate and adaptive immunity involving T cells result in susceptibility to
      skin infections and in hyperreactivity reactions to environmental stimuli which
      in turn determine the course and severity of atopic dermatitis.

PMID- 18802342
TI  - T-cell regulation in helminth parasite infections: implications for inflammatory
      diseases.
AB  - The field of infectious disease immunology is at an exciting intersection with
      new concepts in immune regulation meeting with the dynamics of infectious
      diseases. We discuss how the identification of regulatory mechanisms has already
      helped develop new models to understand helminth infections, which remain among
      the most prevalent chronic diseases in the world today. The epidemiological
      imbalance between helminth infections in developing countries, and intensifying
      allergies and autoimmune pathologies in the industrialised nations, seems to
      reflect a fundamental shift in regulation of immune responsiveness. Experimental
      studies have verified that helminths can downmodulate a range of
      immunopathological conditions, with the regulatory T cell being one of the most
      common mechanisms in play. We discuss further the context of host genetic
      predisposition, together with the impact of infection on the evolution of the
      human immune system, and suggest future strategies to harness our new
      understanding of helminth organisms in order to control both infectious and non
      infectious immunological disorders.

PMID- 18802343
TI  - Immune regulation and tolerance to fungi in the lungs and skin.
AB  - The balance of pro- and anti-inflammatory signaling is a prerequisite for
      successful host/fungal interactions and requires the coordinate actions of both
      innate and adaptive immune systems. Although inflammation is an essential
      component of the protective response to fungi, its dysregulation may
      significantly worsen fungal diseases and limit protective antifungal immune
      responses. The newly described Th17 develop - mental pathway may play an
      inflammatory role previously attributed to uncontrolled Th1 responses and serve
      to accommodate the seemingly paradoxical association of chronic inflammatory
      responses with fungal persistence in the face of an ongoing inflammation. In this
      scenario, unrestricted fungal growth could result from the activation of not only
      pathogenic Th17 cells, but also Th2 cells whose activation is strictly dependent
      on fungal burden. The capacity of regulatory T cells (Tregs) to inhibit aspects
      of innate and adaptive antifungal immunity is required for protective tolerance
      to fungi. Indoleamine 2,3-dioxygenase (IDO) and tryptophan catabolites contribute
      to such a homeostatic condition by providing the host with immune defense
      mechanisms adequate for protection, without necessarily eliminating fungal
      pathogens - which would impair immune memory - or causing an unacceptable level
      of tissue damage. IDO and tryptophan metabolites may prove to be potent
      regulators capable of taming overzealous or heightened inflammatory host
      responses.

PMID- 18802344
TI  - Control of delayed-type hypersensitivity by ocular- induced CD8+ regulatory t
      cells.
AB  - The immunoregulatory pathway from the eye to the peri - pheral immune system is
      comprised of the iris, ciliary body, circulation, thymus and spleen, and is
      influenced by the sympathetic nervous system. At the splenic end of this pathway
      are antigen-specific CD8+ regulatory T cells (Tregs) that mediate directly the
      suppression of T cells that effect delayedtype hypersensitivity (DTH). Here we
      review investigations that demonstrate: (i) the injection of antigen into the
      anterior chamber (AC) attracts circulating monocytic cells to the iris/ciliary
      body that recirculate to the thymus and spleen. In the thymus, ocular-influenced
      monocytic cells activate natural killer T (NKT) cells that migrate to the spleen
      where, in concert with the ocular-influenced monocytic emigrants, they (ii)
      activate CD4+ and CD8+ immunoregulatory T cells. (iii) The generation of the CD8+
      Tregs is dependent on NKT cells in the thymus and the periphery that are
      influenced by the sympathetic nervous system. (iv) The suppression of DTH by the
      AC-induced CD8+ Tregs is dependent on the cytokines transforming growth factor
      Beta and interferon-gamma and is restricted by the expression of major
      histocompatibility complex-associated Qa-1b antigens. In aggregate, this
      oculothymic- splenic pathway is a well-controlled response to ocular injury that
      utilizes a systemic response to antigen that may protect ocular tissue and
      systemic tissue.

PMID- 18802345
TI  - Novel therapeutic strategies by regulatory T cells in allergy.
AB  - Natural CD4+CD25+FoxP3+ regulatory T cells (Treg) actively suppress physiological
      and pathological responses, therefore playing a critical role in controlling
      peripheral tolerance to self antigens and maintaining immune homeostasis. In
      normal individuals, natural Treg and interleukin- 10-secreting Treg are able to
      suppress Th2 responses to allergens, whereas lower levels of Treg or defect in
      their functionality have been described as potential mechanisms for inducing
      allergic diseases. In animal models, adoptive transfer of CD4+CD25+Treg has been
      shown as a promising strategy for preventing or treating allergic disorders.
      Recent studies show that induction of Treg activity is associated with
      suppression of allergic responses in allergic patients treated with specific
      immunotherapy. Herein, I review the potential of Treg as exciting targets for
      developing new immunotherapeutic strategies for treating allergic diseases.

PMID- 18802346
TI  - T-cell regulatory mechanisms in specific immunotherapy.
AB  - Allergen-specific immunotherapy (SIT) is the only treatment which leads to a
      lifelong tolerance against previously disease-causing allergens due to
      restoration of normal immunity against allergens. The description of T-regulatory
      (Treg) cells being involved in prevention of sensitization to allergens has led
      to great interest whether they represent a major target for allergen-SIT and
      whether it would be possible to manipulate Treg cells to increase its efficacy.
      Activationinduced cell death, anergy and/or immune response modulation by Treg
      cells are essential mechanisms of peripheral T-cell tolerance. There is growing
      evidence that anergy, tolerance and active suppression are not entirely distinct,
      but rather represent linked mechanisms possibly involving the same cells and
      multiple suppressor mechanisms. Skewing of allergen-specific effector T cells to
      Treg cells appears as a crucial event in the control of healthy immune response
      to allergens and successful allergen-SIT. The Treg cell response is characterized
      by abolished allergen- induced specific T-cell proliferation and suppressed
      Thelper (Th)1- and Th2-type cytokine secretion. In addition, mediators of
      allergic inflammation that trigger cAMP-associated G-protein-coupled receptors,
      such as histamine receptor-2, may contribute to peripheral tolerance mechanisms.
      The increased levels of interleukin-10 and transforming growth factor-Beta that
      are produced by Treg cells potently suppress IgE production, while simultaneously
      increasing production of non-inflammatory isotypes IgG4 and IgA, respectively. In
      addition, Treg cells directly or indirectly suppress effector cells of allergic
      inflammation such as mast cells, basophils and eosinophils. In conclusion,
      peripheral tolerance to allergens is controlled by multiple active suppression
      mechanisms. It is associated with regulation of antibody isotypes and effector
      cells to the direction of a healthy immune response. By the application of the
      recent knowledge in Treg-dependent mechanisms of peripheral tolerance, more
      rational and safer approaches are awaited for the future prevention and cure of
      allergen hypersensitivity.

PMID- 18802347
TI  - Control and regulation of peripheral tolerance in allergic inflammatory disease:
      therapeutic consequences.
AB  - During the past few years there has been significant pro - gress in understanding
      the mechanisms by which abnormal T-cell responses are generated in allergic
      diseases. Peripheral T-cell tolerance to environmental antigens is crucial for a
      healthy immune response and avoidance of allergy. The balance between T-helper
      (Th)2 cells and T-regulatory (Treg) cells has a critical role in the generation
      of immune responses to environmental antigens. Allergic individuals display an
      aberrant activation and expansion of Th2 cells. It appears that aberrant
      activation of Th2 cells in allergy is secondary to impaired mechanisms of
      peripheral T-cell tolerance that is normally mediated by antigen-specific T-cell
      anergy, Treg cells and suppressive cytokines, IL-10 and TGF-Beta. Therefore, a
      most appealing therapy for allergic diseases would be an allergen-specific
      immunotherapy that reduces Th2 cytokine production and promotes induction of
      anergy, Treg and suppressor cytokines. Such novel therapeutic approaches include
      the use of recombinant allergen-derived peptides, recombinant DNA technology and
      adjuvants. These approaches are employed individually or in combination in order
      to induce T-cell anergy and to utilize innate immunity in order to alter the
      balance of Th1- and Th2-type cytokines and generate or expand Treg in vivo.

PMID- 18802348
TI  - Lung dendritic cells: targets for therapy in allergic disease.
AB  - Dendritic cells (DCs) are crucial in determining the functional outcome of
      allergen encounter in the lung. Antigen presentation by myeloid DCs leads to Th2
      sensitization typical of allergic disease, whereas antigen presentation by
      plasmacytoid DCs serves to dampen inflammation. It is increasingly clear that DCs
      have an antigen presenting function beyond sensitization. DCs therefore
      constitute a novel target for the development of antiallergic therapy aimed at
      the origin of the inflammatory cascade. A careful study of DC biology and of the
      receptors expressed by lung DCs has provided a framework for the discovery of
      novel antiallergic compounds.

PMID- 18802349
TI  - Antigen-based therapies targeting the expansion of regulatory T cells in
      autoimmune and allergic disease.
AB  - Between 5 and 10% of the European population suffer from autoimmune disease,
      whilst allergic disorders affect an even higher frequency, and both these forms
      of immunopathology have increased markedly in recent decades. The need for more
      precise and effective therapeutic strategies drives the investigation of antigen
      based tolerance in rodent models and in patients. The identification of the key
      role T-regulatory cells (Tregs) play in avoidance of immunopathology focused on
      either self or environmental antigens has led to a need to determine whether
      established and novel tolerance-inducing strategies are in fact expanding
      antigenreactive Treg populations. Here we review recent data from mouse and man.
      A consistent thread is that, both in T-helper (Th)1/Th17-driven autoimmune
      disease and in Th2-driven allergic disease, antigen-based tolerance induction
      often promotes an antigen-reactive IL-10 T-cell population whilst reducing the
      pathogenic response. Whether these IL-10- producing cells are from the 'natural'
      Treg population that expresses the forkhead box p3 (Foxp3) transcription factor
      is less clear, and often they are not. We discuss some recent studies that might
      provide insight into how best to expand these protective T cells and highlight
      some outstanding issues requiring further investigation.

PMID- 18802350
TI  - Stem cell transplantation in genetically linked regulatory T-cell disorders.
AB  - T-regulatory disorders are a heterogenous group characterized by autoimmune and
      allergic manifestations of varying onset, severity, and progression. The advent
      of sophisticated molecular and immunologic diagnostic techniques has resulted in
      accurate elucidation of etiopathogenesis of many immunoregulatory disorders
      previously clubbed under the autoimmune umbrella. The severity of presentation
      and progression, early morbidity and mortality, poor quality of life, and
      frequent refractoriness to immunosuppressive therapy has prompted studies of stem
      cell transplantation in many immunoregulatory disorders. The benefits of
      autologous or allogeneic transplantation are related to either suppression and
      reprogramming of the immune system (autologous transplant) or replacement of
      missing elements of immune regulation (allogeneic transplants). Transplant
      methods have steadily improved through a series of studies and trials to have the
      benefits of this approach outweigh the risks of procedure-related toxicities.
      This article summarizes the current status and the future goals of stem cell
      transplantation for T-cell immunoregulatory disorders and reviews advances in
      disease detection, targeted transplant strategies and novel approaches, and the
      pros and cons of transplant in this field.

PMID- 18802351
TI  - Histopathological correlates of the parallel-furrow pattern seen in acral
      melanocytic nevi at dermatoscopy.

PMID- 18802353
TI  - Visceral leishmaniasis infection in a patient with psoriasis treated with
      efalizumab.

PMID- 18802354
TI  - W-plasty technique in tracheal reconstruction: a new technique? An experimental
      study.
AB  - BACKGROUND: Tracheal stenosis and dehiscence of anastomosis due to excessive
      tension are well-known problems after long-segment tracheal resections. The aim
      of this study was to evaluate the efficacy of the W-plasty technique to prevent
      these two complications. METHODS: Animals were divided into a study and a control
      group. Each group consisted of 6 animals. In the control group, we performed a 5
      cm tracheal segment resection, and then reconstruction was performed with an
      interrupted technique with 6/0 Prolene sutures. In the study group, we used the W
      plasty technique with 6/0 Prolene interrupted sutures. The animals were
      sacrificed on the 30th day postoperatively and tracheal resection including the
      entire anastomosis site was performed. The traction and pullout test was applied
      to each specimen and all the specimens were analysed histopathologically. The
      intraluminal diameter and the thickness of the tracheal wall at the level of
      anastomoses were measured by using a micrometer. The pattern of the reaction and
      localization were recorded. RESULTS: The traction and pullout test results were
      131.6 +/- 4.3 g and 187.5 +/- 6.4 g in the control and the study group,
      respectively, which was a significant difference (p = 0.004). The intraluminal
      diameters were 3.3 +/- 1.2 mm and 4.3 +/- 0.9 mm in the control and study group,
      respectively (p = 0.134). In contrast to the control group, early inflammatory
      and late fibroblastic reactions were negative in the study group. CONCLUSION:
      Considering the outcomes of this study, we think that the W-plasty technique has
      much more advantages than the standard techniques in terms of anastomosis
      durability and development of stenosis.

PMID- 18802355
TI  - In vivo and T cell cross-reactivity between walnut, cashew and peanut.
AB  - BACKGROUND: Examination of IgE cross-reactivity among nuts has been limited to in
      vitro experiments. Cross-reactivity studies of nuts at the T cell level are
      difficult to interpret because of the inability to determine which cellular
      responses are from a true sensitization and which are due to cross-reactivity.
      Using a mouse model in which the sensitizing nuts are controlled may provide
      novel methods to investigate in vivo and T cell cross-reactivity. METHODS:
      C3H/HeJ mice were sensitized by intraperitoneal injection of cashew alone
      (monosensitized mice), or cashew plus walnut, utilizing alum as an adjuvant. Both
      groups underwent challenges to cashew, walnut and peanut, with subsequent
      monitoring of anaphylactic reactions. Anaphylactic antibodies were quantified by
      ELISA, and protein allergens were identified by Western blotting. Cellular
      responses were studied via splenocyte proliferation assay and measurement of
      secreted cytokines. RESULTS: The monosensitized mice reacted to cashew and walnut
      during challenges, with significantly weaker reactions induced on challenge with
      peanut. Cross-reactive IgE to walnut and peanut were detected by ELISA, and the
      cross-reactive allergens were identified as vicilin proteins. In cellular assays,
      splenocytes from the monosensitized mice proliferated and produced IL-4 and IL-5
      in response to cashew, walnut and peanut. The cashew- plus walnut-sensitized mice
      experienced stronger clinical reactions to walnut, recognized additional walnut
      allergens and secreted significantly more IL-4 and IL-5 in walnut-stimulated
      splenocyte assays compared to the monosensitized mice. CONCLUSIONS: Cross
      reactivity in vivo was found between cashew and walnut, while cross-reactivity
      among cashew, walnut and peanut was demonstrated at the T cell level.

PMID- 18802356
TI  - Increased surfactant protein a and d expression in acute ovalbumin-induced
      allergic airway inflammation in brown norway rats.
AB  - BACKGROUND: The surfactant proteins SP-A and SP-D, components of the innate
      immune system, are involved in host defence. OBJECTIVE: We tested the hypothesis
      that ovalbumin (OVA) challenge leads to an upregulation of both proteins in
      alveolar epithelial type II cells (AEII) and Clara cells and to an enhanced
      uptake by macrophages. METHODS: After sensitization with OVA and heat-killed
      Bordetella pertussis challenge followed intratracheally with 0.5% OVA on day 13.
      One day after challenge lung tissue and bronchoalveolar lavage fluid (BALF) of
      sensitized NaCl- and OVA-challenged Brown Norway rats were compared with home
      cage controls using qRt-PCR, Western blot and immunohistochemistry. RESULTS:
      After OVA challenge (1) eosinophils increased significantly in the BALF, (2) the
      total amount of SP-A and SP-D was significantly increased in lung tissue, (3) the
      amount of SP-A was significantly and the amount of SP-D was remarkably elevated
      in BALF, and (4) the levels of SP-A and SP-D mRNA in lung tissue were
      significantly elevated. Using quantitative immunohistochemistry, we found (5)
      significantly higher surface fractions of SP-A- and SP-D-labelled AEII, (6) no
      differences in the surface fractions of SP-A- and SP-D-labelled bronchial Clara
      cells, and (7) a significantly increased cell density of unlabelled and SP-A
      labelled macrophages. CONCLUSIONS: Thus, combining molecular biological and
      histological methods we suggest that after OVA challenge (1) AEII but not Clara
      cells show a significantly higher expression of SP-A and SP-D leading also to
      higher amounts of both SPs in BALF and (2) macrophages gather predominantly SP-A.

PMID- 18802357
TI  - Expression and characterization of PGD2 receptors in chronic rhinosinusitis:
      modulation of DP and CRTH2 by PGD2.
AB  - BACKGROUND: Prostaglandin D(2) (PGD(2)) participates in airway inflammation. We
      reported that levels of hematopoietic-type PGD(2) synthase (h-PGDS) in sinonasal
      tissues may play an important role in the pathophysiology of chronic
      rhinosinusitis (CRS). Two PGD(2) receptors have been isolated, DP and CRTH2, but
      whether they participate in CRS remains unclear. We sought to determine the
      expression and characterization of DP and CRTH2 in CRS. METHODS: Expression of DP
      and CRTH2 in nasal polyps (NP) and uncinate process mucosae (UPM) was examined by
      in situ hybridization and immunohistochemistry and evaluated by real-time
      quantitative PCR. h-PGDS, IL-5, eotaxin and RANTES expression was also
      determined. In addition, the effect of PGD(2) on the expression of both receptors
      in UPM was assessed. RESULTS: DP was widely expressed, not only in infiltrating
      inflammatory cells but also in constitutive cells such as vascular endothelial
      cells and ciliated columnar epithelia. CRTH2 was selectively expressed in
      inflammatory cells and some glands. Significantly greater levels of DP mRNA and
      conversely decreased levels of CRTH2 mRNA were observed in NP compared with UPM.
      DP and CRTH2 mRNA levels were not only positively and inversely correlated with
      levels of h-PGDS but also with eotaxin, respectively. Furthermore, addition of
      PGD(2) significantly increased DP expression and conversely reduced CRTH2
      expression in UPM. CONCLUSIONS: These results suggest that distinct expression of
      DP and CRTH2 is associated with the pathophysiology of CRS, including NP
      formation, and the expression of these receptors may be regulated by h-PGDS and
      PGD(2).

PMID- 18802358
TI  - A common exonic variant of interleukin21 confers susceptibility to atopic asthma.
AB  - BACKGROUND: Interleukin (IL)-21, an IL-2 family multifunctional cytokine, is
      produced by activated CD4+ T cells and is known to potentially affect growth,
      survival and function of numerous immune cells. As IL-21 regulates IgE
      production, a key mediator of various allergic disorders and asthma, it is a
      prime candidate gene for studying atopic asthma. METHODS: In atopic asthma,
      analyses of four single nucleotide polymorphisms (SNP; C1455T, G1472T, C5250T and
      C8381T), a tetranucleotide microsatellite repeat (GAAT)(n) and their haplotypes
      were performed, and serum total IgE (TsIgE) was determined in ethnically matched
      unrelated patients (n = 255), unrelated controls (n = 245) and nuclear families
      (n = 140). Correlation between an exonic SNP C5250T in the asthmatics with serum
      IL-21 levels was also made. RESULTS: In both the case-control and family study
      groups, the exon-3 polymorphism C5250T of the IL21 gene was significantly
      associated with atopic asthma and TsIgE. The C5250T polymorphism was found to
      affect the concentration of serum IL-21 levels in atopic asthmatics. Also, this
      observation was supported by the structural alteration in IL21 mRNA as predicted
      by mfold software. Further, our haplotypic studies indicated that while minor
      haplotypes 4_C_T_C_C and two locus haplotype T_C were associated with asthma in
      the case-control cohort, none of the major haplotypes was found to be associated
      with either asthma or TsIgE levels. CONCLUSION: Our study provides evidence that
      IL21 is associated with atopic asthma, TsIgE and serum IL-21 levels. Thus, it may
      initiate further research to elucidate the role of the IL21 gene in asthma
      pathogenesis.

PMID- 18802359
TI  - Cysteinyl leukotrienes induce macrophage inflammatory protein-1 in human
      monocytes/macrophages.
AB  - BACKGROUND: Macrophage inflammatory protein-1alpha (MIP-1alpha) and MIP-1beta are
      known for their chemotactic and proinflammatory effects on monocytes/macrophages
      which have a cysteinyl leukotriene 1 (CysLT(1)) receptor. METHODS: We examined
      MIP-1alpha and MIP-1beta production stimulated by CysLTs (LTC(4), LTD(4), and
      LTE(4)) in THP-1 cells, a human monocytic leukemia cell line, and peripheral
      blood mononuclear cells (PBMCs). Moreover, we examined the inhibitory effect of
      pranlukast, a CysLT(1) receptor antagonist, and inhibitors of three major mitogen
      activated protein kinases (MAPK) on the induction of MIP-1alpha and MIP-1beta
      production by CysLTs. RESULTS: ELISA demonstrated that CysLTs induced MIP-1alpha
      and MIP-1beta production in THP-1 cells and PBMCs. PCR demonstrated that LTD(4)
      increased MIP-1alpha and MIP-1beta mRNA expressions in THP-1 cells. Pranlukast
      blocked MIP-1alpha and MIP-1beta production promoted by LTD(4) in THP-1 cells and
      PBMCs. Moreover, an inhibitor of extracellular signal-regulated kinase (ERK)
      attenuated the induction of MIP-1alpha and MIP-1beta production by LTD(4) in THP
      1 cells whereas the inhibitors of c-Jun NH2-terminal kinase or p38 MAPK did not.
      CONCLUSION: CysLTs induce MIP-1alpha and MIP-1beta production mediated by ERK via
      binding to the CysLT(1) receptor in human monocytes/macrophages.

PMID- 18802360
TI  - Bronchial diffusing capacity of nitric oxide is increased in patients with
      allergic rhinitis.
AB  - BACKGROUND: Exhaled nitric oxide (NO) measurement at multiple exhalation flow
      rates allows calculation of flow-independent NO parameters: alveolar NO
      concentration, bronchial NO flux, bronchial diffusing capacity of NO and
      bronchial wall NO concentration. METHODS: In the present study, we measured the
      flow-independent NO parameters and inflammatory markers in exhaled breath
      condensate (EBC) and in serum in 14 patients with seasonal allergic rhinitis (AR)
      without asthma, and in 14 age- and sex-matched healthy volunteers. RESULTS: At
      symptomatic stage before the treatment, patients with AR had higher bronchial
      wall diffusing capacity of NO than healthy volunteers (p = 0.024), but there were
      no differences in bronchial wall NO concentration or alveolar NO concentration.
      Patients with AR had also increased 8-isoprostane levels in the EBC (p = 0.040),
      and increased serum levels of IgE (p = 0.002) and eosinophil cationic protein
      (ECP; p = 0.027). Two-week treatment with nasal glucocorticoid mometasone
      decreased symptom scores and serum ECP levels but had no effect on NO parameters
      or 8-isoprostane levels in EBC. CONCLUSIONS: Noninvasive markers of airway
      inflammation showed subclinical lower airway inflammation in patients with AR
      without asthma, but short-term treatment with nasal glucocorticoids did not
      affect most of the markers of lower airway inflammation.

PMID- 18802361
TI  - Comparative study of cluster and conventional immunotherapy schedules with
      dermatophagoides pteronyssinus in the treatment of persistent allergic rhinitis.
AB  - BACKGROUND AND OBJECTIVES: Allergy to house dust mite is one of the most common
      causes of allergic rhinitis (AR) in China. We sought to compare the efficacy and
      safety of a 6-week cluster schedule of specific immunotherapy with that of a 14
      week conventional schedule for the treatment of subjects with persistent AR.
      METHODS: The trial was a prospective and randomized study involving 96 patients
      with persistent AR, aged 14-60 years, who were allergic to Dermatophagoides
      pteronyssinus. While 48 patients were randomly assigned to the cluster schedule
      reaching the maintenance dose within 6 weeks, the other 48 were randomly assigned
      to the conventional schedule reaching the maintenance dose within 14 weeks.
      Eighty-nine patients completed a 1-year treatment course. While kinetic changes
      in clinical efficacy and adverse reactions were observed during the treatment,
      quality of life, cutaneous reactivity and serum-specific immunoglobulin E to
      Dermatophagoides pteronyssinus were measured before and after treatment. RESULTS:
      The cluster schedule reduced the time to reach the maintenance dose by 57% and
      caused mild systemic adverse reactions after 1.0% of injections (6.7% of
      patients), with no differences in comparison with the conventional schedule.
      Cluster specific immunotherapy led to decreases in clinical symptoms and earlier
      use of medication than did the conventional schedule. Similar improvements in
      quality of life and reduced cutaneous reactivity without significant changes in
      specific immunoglobulin E were observed in both groups after 1 year. CONCLUSIONS:
      The cluster schedule is a safe alternative to the conventional schedule with the
      advantage of achieving clinical effectiveness sooner.

PMID- 18802362
TI  - Expression of tissue factor by eosinophils in patients with chronic urticaria.
AB  - BACKGROUND: Although several cases of chronic urticaria (CU) are currently
      regarded as autoimmune in origin, associated with histamine-releasing
      autoantibodies, an activation of blood coagulation via tissue factor (TF) and a
      strong expression of TF in lesional skin have been described. Eosinophils, which
      are involved in CU skin lesions, have recently been demonstrated as the major
      source of TF in human blood. We assessed whether eosinophils are the cellular
      source of TF in CU skin lesions. METHODS: Twenty patients with severe CU were
      studied. Skin biopsy specimens were taken from wheals. The control group
      consisted of specimens of perilesional normal skin from different types of skin
      tumours (10) and various skin disorders with non-eosinophilic infiltrates,
      including leukocytoclastic vasculitis (7), lichen planus (8) and mastocytosis
      (3). TF expression was evaluated by immunohistochemical methods using an anti-TF
      monoclonal antibody. Co-localization of TF and eosinophil cationic protein, a
      classic cell marker of eosinophils, was investigated by double-staining studies
      using 2 specific monoclonal antibodies in the 4 specimens showing the highest TF
      reactivity scores. RESULTS: All specimens from patients with CU clearly showed TF
      expression that was absent in all normal control specimens (p = 0.0001) and in
      the skin disorders with non-eosinophilic infiltrates (p = 0.001-0.0001). The
      double-staining experiments for TF and eosinophil cationic protein clearly showed
      that the TF-positive cells were eosinophils. CONCLUSIONS: Eosinophils are the
      main source of TF in CU lesional skin. This finding highlights the role of these
      cells in the pathophysiology of CU and might pave the way for new therapeutic
      strategies.

PMID- 18802363
TI  - Effects of long-term cholecalciferol supplementation on mineral metabolism and
      calciotropic hormones in chronic kidney disease.
AB  - BACKGROUND: Data on the efficacy and safety of long-term vitamin D
      supplementation in chronic kidney disease (CKD) are scarce. We assessed the
      effects of the 12-month vitamin D(3) treatment on mineral metabolism and
      calciotropic hormones in patients with CKD stages 2-4. METHODS: Eighty-seven
      patients (mean age 66 years, men/women 33/54) were randomized to cholecalciferol
      treatment with either 5,000 or 20,000 IU/week. Serum calcium, phosphate,
      25(OH)D(3), 1,25(OH)(2)D(3), PTH and urinary mineral concentrations were obtained
      at baseline and after 4, 8 and 12 months. RESULTS: The median serum mineral
      concentrations were normal and not changed throughout the study. The number of
      hypercalciuric patients slightly increased with higher dose, but no sustained
      rise in calciuria was present. Vitamin D insufficiency/deficiency was revealed in
      72 (83%) patients at baseline and 37 (43%) at month 12. The 25(OH)D(3) levels
      increased more with higher dose; a rise in 1,25(OH)(2)D(3) was less impressive.
      The parathyroid hormone (PTH) concentrations were reduced, but the number of
      subjects with PTH below the lower limit for CKD stage 3 increased equally with
      both doses. CONCLUSIONS: Vitamin D insufficiency/deficiency in CKD significantly
      improved after the 12-month cholecalciferol treatment, with higher dose being
      more effective and equally safe. Further studies of vitamin D(3) effects on bone
      metabolism are warranted.

PMID- 18802364
TI  - Acute kidney injury - scientific evidence driving change in patient management.
      Introduction.

PMID- 18802365
TI  - Definition and classification of acute kidney injury.
AB  - Changes in urine output and glomerular filtration rate are neither necessary nor
      sufficient for the diagnosis of renal pathology. Yet no simple alternative for
      the diagnosis currently exists. Until recently, there has been no consensus as to
      diagnostic criteria or clinical definition of acute renal failure. Depending on
      the definition used, acute renal failure has been reported to affect from 1 to
      25% of ICU patients and has led to mortality rates from 15 to 60%. The RIFLE
      criteria were developed to standardize the diagnosis of acute renal failure and
      in the process the term acute kidney injury (AKI) has been proposed to encompass
      the entire spectrum of the syndrome from minor changes in renal function to
      requirement for renal replacement therapy. Thus, AKI is not acute renal failure
      but a more general description. Small changes in kidney function in hospitalized
      patients are important and are associated with significant changes in short and
      possibly long-term outcomes. The RIFLE criteria provide a uniform definition of
      AKI and have now been validated in numerous studies.

PMID- 18802366
TI  - The epidemiology of severe acute kidney injury: from BEST to PICARD, in acute
      kidney injury: new concepts.
AB  - Various definitions of acute kidney injury (AKI) exist, making comparisons among
      studies difficult. Despite this, significant changes have occurred in the
      epidemiology of AKI during the last decade. Recent studies, including PICARD and
      BEST, have examined the epidemiology of ICU-related AKI in the USA and worldwide,
      respectively, and found that AKI remains a major cause of morbidity and
      mortality. The incidence of AKI has increased, most likely due to a trend toward
      older, more severely and chronically ill patients admitted to the hospital.
      Sepsis and multi-organ system failure continue to be strongly associated with
      AKI, as well as pre-morbid chronic kidney disease. The proportion of patients
      with AKI requiring dialysis is high. The mortality of ICU-related AKI, although
      still very elevated, may be decreasing. Understanding these changes, in the
      context of standardized definitions, will be essential for the design of
      successful interventional studies.

PMID- 18802367
TI  - Biomarkers for the diagnosis of acute kidney injury.
AB  - The identification of acute kidney injury relies on tests like blood urea
      nitrogen and serum creatinine that were identified and incorporated into clinical
      practice several decades ago. This review summarizes clinical studies of newer
      biomarkers that may permit earlier and more accurate identification of acute
      kidney injury. The urine may contain sensitive and specific markers of kidney
      injury that are present due to either impaired tubular reabsorption and
      catabolism of filtered molecules or release of tubular cell proteins in response
      to ischemic or nephrotoxic injury. Many potential markers have been studied.
      Promising injury markers in the urine include N-acetyl-beta-D-glucosaminidase,
      neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, and
      interleukin-18. New biomarkers of kidney injury hold the promise of substantially
      improving the diagnostic approach to acute kidney injury. Adequately powered
      clinical studies of multiple biomarkers are needed to qualify the biomarkers
      before they can be fully adopted in clinical practice. Once adopted, more
      sensitive biomarkers of acute kidney injury hold the potential to transform the
      care of patients with renal disease.

PMID- 18802368
TI  - Imaging techniques in acute kidney injury.
AB  - Multi-photon microscopy, along with advances in other imaging modalities, allows
      investigators the opportunity to study dynamic events within the functioning
      kidney. These emerging technologies enable investigators to follow complex
      heterogeneous processes in organs such as the kidney with improved spatial and
      temporal resolution, and sensitivity. Furthermore, the ability to obtain
      volumetric data (3-D) makes quantitative 4-D (time) analysis possible. Finally,
      use of up to three fluorophores concurrently in multi-photon microscopy allows
      for three different or interactive processes to be observed simultaneously.
      Therefore, this approach complements existing molecular, biochemical,
      pharmacologic and radiologic techniques by advancing data analysis and
      interpretation to subcellular levels for molecules without the requirement for
      fixation. Its use in acute kidney injury is in its infancy but offers much
      promise for unraveling the complex interdependent processes known to contribute
      to cell injury and organ failure. Also, recent advances in other imaging
      techniques offer potential clinical diagnostic tools to study acute kidney injury
      in animal models and in patients.

PMID- 18802369
TI  - New insights on intravenous fluids, diuretics and acute kidney injury.
AB  - Acute kidney injury (AKI) is commonly and increasingly encountered in patients
      with critical illness. Fluid therapy is the cornerstone for the prevention and
      management of critically ill patients with AKI. New data have emerged that have
      raised concern that specific types of fluid (i.e. hydroxyethylstarch) may either
      contribute to or exacerbate AKI. Additional data have accumulated to indicate
      that the unnecessary accumulation of fluid and volume overload can negatively
      impact clinical outcomes. This finding may be further compounded in patients with
      oliguric AKI where solute and free water elimination are impaired. Diuretic
      therapy in AKI remains controversial. However, diuretic use is common, despite a
      paucity of evidence to show improved clinical outcomes. There are few therapeutic
      interventions proven to impact the clinical course and outcome of critically ill
      patients with established AKI. Current management strategies center largely on
      supportive care, with rapid resuscitation, removal of the stimulus contributing
      to AKI, judicious avoidance of complications, and allowing time for recovery. In
      this review, we explore recent insights on intravenous fluid therapy, volume
      overload, and diuretic therapy in the context of the critically ill patients with
      AKI.

PMID- 18802370
TI  - Outcome prediction for patients with acute kidney injury.
AB  - BACKGROUND/AIMS: To review the currently available severity scores to predict
      outcome of acute kidney injury (AKI) patients, to discuss the problems with such
      scores, and to provide information for the development of more accurate AKI
      severity scores in the future. METHODS: Literature review and multivariate
      analysis using a large international database for AKI. RESULTS: Although general
      severity scores have good discrimination and calibration abilities to predict
      outcome of critically ill patients, the accuracy of these systems for AKI
      patients has been questioned. To improve prediction ability, multiple AKI
      severity scores have been published in the literature. However, most of these
      scores were developed and tested in a single center, or if multicentric, they
      were confined to a single country. Seven variables (mechanical ventilation,
      bilirubin, age, oliguria, hypotension, sepsis and platelet count) are often found
      as common risk factors in these severity scores and should be included in future
      AKI severity scores. Although several studies have consistently reported that
      both low creatinine and high urea at the start of RRT are related to worse
      outcome in AKI patients, they might not improve prediction ability. CONCLUSION:
      Using available information and a large database collected internationally, a
      more accurate score for AKI is likely to be developed.

PMID- 18802371
TI  - Acute kidney injury: new concepts, renal recovery.
AB  - BACKGROUND/AIMS: Long-term outcome after critical illness is important. After
      acute kidney injury (AKI) one measurement of such long-term outcome is assessment
      of renal recovery. METHODS: A literature search was performed using the Medline
      database from 1960 to the present. The attempt was to include major clinical
      trials and other systematic reviews published in the field of renal recovery
      after critical illness. RESULTS: More than 15 studies have covered the topic of
      renal outcome after intensive care, but the results are ambiguous. Studies from
      the mid-1990s showed that AKI survivors were at great risk of becoming dialysis
      dependent for life, with non-recovery reported at around 30%. Later
      investigations found lower risks, with non-recovery between 5 and 8% depending on
      the choice of continuous or intermittent renal replacement therapies. CONCLUSION:
      Continuous renal replacement therapies may be associated with better chances of
      renal recovery. Determining when and how to measure long-term renal outcome
      remains a matter of controversy.

PMID- 18802372
TI  - Inflammation in acute kidney injury.
AB  - Ischemia-reperfusion injury (IRI) is one of the major causes of acute kidney
      injury (AKI) and evidence supporting the involvement of both innate and adaptive
      immunity in renal IRI has accumulated in recent years. In addition to leukocytes,
      kidney endothelial cells promote inflammation after IRI by increasing adhesion
      molecule expression and vascular permeability. Kidney tubular epithelial cells
      increase complement binding and upregulate toll-like receptors, both of which
      lead to cytokine/chemokine production in IRI. Activation of kidney resident
      dendritic cells, interferon-gamma-producing neutrophils, infiltrating
      macrophages, CD4+ T cells, B cells and invariant natural killer T cells are all
      implicated in the pathogenesis of AKI. The complex interplay between innate and
      adaptive immunity in renal IRI is still not completely understood, but major
      advances have been made. This review summarizes these recent advances to further
      our understanding of the immune mechanisms of acute kidney injury.

PMID- 18802373
TI  - Antioxidants. Do they have a place in the prevention or therapy of acute kidney
      injury?
AB  - Over the past several years, advances in our understanding of the pathogenesis of
      acute kidney injury (AKI) have demonstrated the role of oxidant stress and
      reactive oxygen metabolites (ROM) in the development of AKI in a variety of
      clinical settings. This review serves to define the pathways that lead to the
      generation of ROM following a variety of insults, as well as to review the
      current literature concerning the role of antioxidant therapy in the prevention
      and treatment of AKI in several clinical settings. Investigators have explored
      the potential therapeutic role of anti-oxidants in both experimental animal
      models and human studies of AKI in several clinical settings, including cardiac
      and aortic occlusive surgeries, sepsis, drug nephrotoxicity (cisplatin and
      gentamicin), as well as rhabdomyolysis. While the experimental animal studies
      have generally been more successful, taken together this literature supports the
      hypothesis that oxidant stress-induced production of ROM plays a major role in
      the pathogenesis of many forms of AKI, and continues to suggest the potential
      utility of antioxidant therapy in human AKI. Ongoing trials in concert with
      improved diagnostic techniques will hopefully lead to improved outcomes in the
      setting of AKI through the prophylactic or early therapeutic use of antioxidant
      therapy.

PMID- 18802374
TI  - The bioartificial kidney and bioengineered membranes in acute kidney injury.
AB  - The treatment of severe acute kidney injury (AKI) with dialysis or hemofiltration
      remains suboptimal with high levels of morbidity and mortality. Current renal
      replacement therapies substitute for the small solute clearance function of the
      kidney but do not replace the lost reclamation, metabolic and endocrine functions
      of this organ. Cell therapy and tissue engineering offer hope of fuller
      replacement of kidney function in renal failure patients. A renal tubule assist
      device (RAD) that includes a conventional hemodialysis filter and a bioreactor
      containing living renal proximal tubule cells has been successfully engineered.
      Differentiated activity of these cells and survival advantages have been
      demonstrated in large-animal models of sepsis and AKI. Data from phase I/II and
      phase II clinical studies have shown that the addition of renal tubule cell
      therapy to conventional continuous renal replacement therapy (CRRT) treatment
      resulted in a significant clinical impact on survival, and that RAD treatment
      demonstrated an acceptable safety profile. Another substantive advance for the
      treatment of AKI will be the development of nanofabrication technology to further
      improve the clearance function of the kidney to replicate glomerular
      permselectivity while retaining high rates of hydraulic permeability. New
      developments in this translational research area will improve the unmet medical
      needs of patients with renal failure.

PMID- 18802375
TI  - Septic acute kidney injury: new concepts.
AB  - Acute kidney injury (AKI) is a serious condition that affects many ICU patients.
      The most common causes of AKI in ICU are severe sepsis and septic shock. The
      mortality of AKI in septic critically ill patients remains high despite of our
      increasing ability to support vital organs. This is partly due to our poor
      understanding of the pathogenesis of sepsis-induced renal dysfunction. However,
      new concepts are emerging to explain the pathogenesis of septic AKI, which
      challenge previously held dogma. Throughout the past half century, septic AKI has
      essentially been considered secondary to kidney ischemia. However, recent models
      of experimental sepsis have challenged this notion by demonstrating that, in
      experimental states, which simulate the hemodynamic picture most typically seen
      in man (e.g. hyperdynamic sepsis) renal blood flow, actually increases as renal
      vascular resistance decreases. These experimental observations provide proof of
      concept that septic AKI can occur in the setting of renal hyperemia and that
      ischemia is not necessary for loss of glomerular filtration rate (GFR) to occur.
      They also suggest that similar hemodynamic event may occur in man. In addition,
      preliminary studies in septic sheep show that, when ATP is measured using an
      implanted phosphorus coil and magnetic resonance technology, renal bioenergetics
      are preserved in the setting of advanced septic shock. While these findings need
      to be confirmed, they challenge established paradigms and offer a new conceptual
      framework of reference for further investigation and intervention in man.

PMID- 18802376
TI  - Cardiac surgery-associated acute kidney injury: putting together the pieces of
      the puzzle.
AB  - BACKGROUND: Acute kidney injury (AKI) is a common problem in the context of
      cardiac surgery. There are both similarities and differences with AKI occurring
      in other clinical scenarios. In this paper, we discuss those aspects of AKI that
      are particular to cardiac surgery-associated AKI (CSA-AKI), with emphasis on
      recent advances in the field. METHODS: We summarize the recent literature
      relating to CSA-AKI, focusing on epidemiology, pathophysiology, risk prediction
      and prevention. RESULTS: The Acute Kidney Injury Network (AKIN) criteria for the
      diagnosis and severity of AKI are a useful framework within which future
      epidemiological studies of AKI may be considered. Percent change in serum
      creatinine remains a sensitive and clinically relevant continuous measure of
      declining kidney function. New biomarkers of diagnosis are currently being
      validated, while biomarkers of prognosis are lacking. Notably, intraoperative
      antifibrinolytic therapy effects invalidate 'tubular proteinuria' biomarkers.
      Better characterization of genetic predisposition to CSA-AKI may enhance risk
      prediction, since currently available clinical models lack precision,
      particularly for the important clinical endpoint of new renal replacement
      therapy. CONCLUSIONS: CSA-AKI remains a clinically relevant problem for 5-10% of
      cardiac surgery patients and is associated with adverse clinical outcomes. Small
      changes in serum creatinine are important and should not be ignored. The overall
      incidence of new dialysis after cardiac surgery remains low.

PMID- 18802377
TI  - Radiocontrast-induced acute kidney injury.
AB  - Many radiographic studies and procedures use iodinated contrast media and
      consequently pose the risk of contrast-induced acute kidney injury (AKI). This is
      an important complication, which accounts for a significant number of cases of
      hospital-acquired renal failure associated increased hospital length of stay and
      increased mortality. Sustained reductions in renal blood flow, hypoxic injury,
      direct cellular toxicity by the contrast media, and superimposed organ injury are
      all believed to play a role in this form of AKI. Avoidance of dehydration and
      multimodality prevention measures may reduce rates of this problem in patients at
      risk. Contrast-induced AKI is likely to remain a significant challenge for
      specialists in the future since the patient population is aging, chronic kidney
      disease and diabetes are coming more common, and use of iodinated contrast is
      growing.

PMID- 18802378
TI  - Acute kidney injury: new concepts. Hepatorenal syndrome: the role of
      vasopressors.
AB  - Type 1 hepatorenal syndrome (HRS) is prerenal failure specific to decompensated
      cirrhosis. In patients with HRS, there is marked splanchnic/systemic vasodilation
      resulting in arterial hypotension, arterial baroreceptor unloading,
      overstimulation of the sympathetic nervous and renin-angiotensin systems. This
      reflex neurohumoral hyperactivity via endogenous vasoconstrictors/vasopressors
      such as angiotensin II and noradrenaline induces arterial vasoconstriction in
      different extrasplanchnic vascular beds (including preglomerular arteries in the
      kidneys). Decreased arterial pressure (i.e. low renal perfusion pressure) and
      preglomerular vasoconstriction are thought to play a major role in the decline of
      the glomerular filtration rate (GFR). Nonrandomized studies in patients with HRS
      have shown that the administration of a splanchnic vasoconstrictor (vasopressin
      analogue or alpha(1)-adrenoceptor agonist), usually combined with intravenous
      albumin, causes increases in arterial pressure, arterial baroreceptor uploading,
      decreased neurohumoral activity, decreased renal vascular resistance, and
      increased GFR. Randomized clinical trials have shown that treatment with a
      combination of the vasopressin analogue terlipressin and intravenous albumin
      improves renal function in patients with type 1 HRS. Vasopressor therapy with
      terlipressin plus intravenous albumin is the medical treatment of choice for type
      1 HRS.

PMID- 18802379
TI  - Distant-organ changes after acute kidney injury.
AB  - Acute kidney injury (AKI) contributes significantly to morbidity and mortality in
      both adults and children. While clinical data suggest that AKI contributes to and
      exacerbates multiorgan failure, the physiologic and molecular mechanisms
      responsible for these interactions were previously unknown. New data linking AKI
      with distant-organ dysfunction includes evidence that inflammatory cascades are
      abnormal after organ injury. Leukocyte trafficking, cytokine expression, cell
      adhesion-molecule expression and membrane ion and water-channel expression in
      distant organs are deranged after kidney injury. The responses to oxidative
      stress after AKI are also altered, suggesting complex mechanisms of crosstalk
      between the injured kidney and distant organs. Novel methodologies, including
      genomics and proteomics, are now being employed to unravel interorgan
      communication to accelerate clinically meaningful discovery for this serious
      disease.

PMID- 18802380
TI  - Emerging therapies for extracorporeal support.
AB  - Dialytic therapies have undergone major technological developments in the last
      decade and emerging techniques are promoted not only for acute kidney injury, but
      also for sepsis, acute decompensated heart failure, and acute and acute-on
      chronic liver failure. New devices specifically target the pathophysiological
      mechanisms involved in these conditions. In septic shock and sepsis, high-volume
      hemofiltration, coupled plasma filtration adsorption, cascade hemofiltration and
      high permeability hemofiltration enhance removal of pro-inflammatory mediators,
      while in liver failure, Molecular Adsorbents recycling System (MARS) and
      Prometheus favor the elimination of albumin-bound toxins such as bilirubin. In
      acute decompensated heart failure, simplified ultrafiltration machines are used
      to reach negative fluid balance in a minimalist setting. In the context of
      limited resources and growing expansion in the availability of technologies, a
      critical assessment is required and the use of these devices needs to be put in
      perspective. This article reviews the mechanisms, advantages and limitations of
      these techniques along with the current evidence available regarding their
      influence on major clinical outcomes.

PMID- 18802381
TI  - Druggable targets and targeted drugs: enhancing the development of new
      therapeutics.
AB  - The advent of functional genomics, proteomics, chemi-informatics, and other
      systems-based scientific approaches have raised expectations of novel targets for
      drug discovery and design. Similarly, advances in materials sciences and
      biomolecular chemistries raised the prospects of highly targeted therapeutics
      that maximize efficacy while minimizing systemic toxicity. In spite of these
      advances, the gross measure of approvable drug output is declining, with only 17
      new chemical entities approved by the FDA in 2007. This is in the face of high
      levels of R&D expenditures in both public and private sectors, and suggests that
      new, integrative approaches are needed in order to maximally exploit the rapidly
      expanding knowledge of potential drug and disease targets. The convergence of
      novel druggable targets with new chemical entities that can be specifically
      targeted to disease-causing sites and genes represents one means of creating
      highly efficacious and specific therapies. The approaches that are needed to
      facilitate such convergence include merging computational methods, systems
      biology, and gene-linked categorization of diseases with the use of appropriate
      drug delivery vehicles.

PMID- 18802382
TI  - Overview of the topic.

PMID- 18802383
TI  - Meaning of SPC.

PMID- 18802384
TI  - Importance of SPC.

PMID- 18802385
TI  - Framework and methodology.

PMID- 18802386
TI  - Lymphomas.

PMID- 18802387
TI  - Leukemias.

PMID- 18802388
TI  - Breast cancer (female).

PMID- 18802389
TI  - Lung cancer.

PMID- 18802390
TI  - Cancers of the head and neck.

PMID- 18802391
TI  - Gastrointestinal cancers.

PMID- 18802392
TI  - Genitourinary cancers.

PMID- 18802393
TI  - Gynecologic cancers.

PMID- 18802394
TI  - Skin cancers.

PMID- 18802395
TI  - Pediatric cancers.

PMID- 18802396
TI  - Summary of significant SPC associations.

PMID- 18802397
TI  - Population health priorities.

PMID- 18802398
TI  - Low circulating levels of ProMMP-2 are associated with adverse prognosis in
      bladder cancer.
AB  - OBJECTIVES: In this study the serum levels of proMMP-2, active MMP-2, TIMP-2 and
      MMP-2:TIMP2 complex were evaluated. We also studied the correlation of these
      parameters with clinicopathological parameters in patients suffering from bladder
      carcinoma and outcome in this patient group. METHODS: The levels of circulating
      proMMP-2, active MMP-2, proMMP-9, TIMP-1, TIMP-2 and MMP-2:TIMP-2 complex of 84
      patients with bladder cancer were measured by ELISA. The proMMP-2 and TIMP-2
      immunoreactive proteins were studied. These results were compared to
      clinicopathological parameters and patient outcome. RESULTS: Low circulating
      proMMP-2 levels significantly correlated with poor prognosis. The 5-year disease
      specific survival rate was 46% in patients with high levels of proMMP-2 versus
      23% in patients with low proMMP-2 levels (p = 0.011). Low TIMP-2 levels could
      also present as a marker of poor prognosis. In this study, the 5-year disease
      specific survival in patients with low circulating TIMP-2 levels was 19% compared
      to 66% in patients with high TIMP-2 levels (p = 0.004). CONCLUSION: These results
      indicate that high levels of circulating proMMP-2 and TIMP-2 levels are both
      associated with a better clinical course; moreover, total proMMP-2 is an
      independent prognostic marker of bladder cancer progression.

PMID- 18802399
TI  - c-myc antisense oligonucleotides sensitize human colorectal cancer cells to
      chemotherapeutic drugs.
AB  - BACKGROUND/AIMS: Overexpression of the c-myc oncogene frequently occurs in both
      colon tumors and colon carcinoma cell lines. We examined the sensitization of
      human colorectal cancer cells to chemotherapeutic drugs using c-myc antisense
      (AS) phosphorothioate oligonucleotides ([S]ODNs). METHODS: Cancer cells were
      treated with c-myc [S]ODNs, taxol, 5-fluorouracil (5-FU), doxorubicin and
      vinblastine individually and in combination. The antiproliferative effects, type
      of interaction between c-myc [S]ODNs and cytotoxic drugs, cell cycle, apoptosis
      and expression of cell-cycle- and apoptosis-regulatory genes were evaluated.
      RESULTS: After treatment with c-myc AS[S]ODNs, the growth of cancer cells was
      markedly inhibited in a dose- and time-dependent manner and the levels of c-myc
      mRNA and protein were greatly decreased (p < 0.0001). The combinations of c-myc
      AS[S]ODNs and cytotoxic drugs produced greater growth inhibition of human
      colorectal cancer cells compared to single treatment with either c-myc AS[S]ODNs
      (p < 0.006) or cytotoxic drugs (p < 0.0001). These combinations exhibited time-
      and dose-dependent additive and/or synergistic antiproliferative effects. Cancer
      cells treated with cytotoxic drugs were growth arrested in the S phase. In
      contrast, cells treated with either c-myc AS[S]ODNs or by the combination of c
      myc AS[S]ODNs and cytotoxic drugs were growth arrested in the G(2)/M and S
      phases. The combination treatments also exhibited a marked apoptotic effect
      compared to single treatments. c-myc AS[S]ODN treatment reduced the mRNA levels
      of Bcl2, BclxL, cdk2, cyclin E1, cdk1 and cyclin B1, while increasing the mRNA
      levels of p21, p27, bax and caspase-3. CONCLUSION: This two-hit approach may be
      important in the quest to overcome drug resistance in cancer patients whose
      tumors carry an overexpressed c-myc gene.

PMID- 18802400
TI  - Functional implications of HNK-1 expression on invasive behaviour of melanoma
      cells.
AB  - HNK-1 epitope, also known as CD57, is expressed on a wide range of cells and has
      been related to cell to cell and cell to extracellular matrix interactions.
      Expression of the HNK-1 epitope has been considered a prognostic factor in
      several tumours, as it has been associated with the risk of metastasis. HNK-1 has
      been found to be expressed on uveal and cutaneous melanoma and proposed as a
      useful marker of the risk of metastasis. We have analysed the HNK-1 expression on
      a large panel of melanoma cell lines, the involvement of this epitope in melanoma
      cell adhesion, as well as its migrative and invasive behaviour. HNK-1 was highly
      expressed in 12.9% of melanoma cell lines, and in vitro experiments using
      invasive melanoma cell lines demonstrated that an HNK-1 blockade reduces cell
      adhesion to extracellular matrix as well as their migrative and invasive ability.
      These data support the functional relevance of HNK-1 expression in metastatic
      melanoma.

PMID- 18802401
TI  - Dissecting the role of the 3-phosphoinositide-dependent protein kinase-1 (PDK1)
      signalling pathways.
AB  - The 3-phosphoinositide-dependent protein kinase-1 (PDK1) mediates the cellular
      effect of insulin and growth factors by activating a group of kinases including
      PKB/Akt, S6K, RSK, SGK and PKC isoforms. PDK1 possesses two regulatory domains
      namely a Pleckstrin Homology (PH) domain that binds to the phosphatidylinositol
      3,4,5-trisphosphate [PtdIns(3,4,5)P(3)] second messenger, and a substrate binding
      site termed the PIF-pocket. Employing a combination of biochemical, structural
      and mouse knock-in approaches we have been able to define the roles that the
      regulatory domains on PDK1 play. We have established that binding of PDK1 to
      PtdIns(3,4,5)P(3) is essential for efficient activation of PKB isoforms as well
      as for maintaining normal cell size and insulin sensitivity. In contrast, the PIF
      substrate binding pocket of PDK1 is not required for PKB activation, but is
      necessary for PDK1 to activate all of its other substrates.

PMID- 18802402
TI  - Localization of aurora A and aurora B kinases during interphase: role of the N
      terminal domain.
AB  - Aurora kinases possess a conserved catalytic domain (CD) and a N-terminal domain
      (ND) that varies in size and sequence. We have previously reported that the N
      terminal domain of AuroraA (AurA) participates in the localization of the kinase
      to the centrosome in interphase. AuroraB (AurB) is a chromosome passenger protein
      and its N-terminal domain is not necessary for its localization or function
      during mitosis. Using various combinations of GFP-AurA and AurB protein domains
      we show that AurB N-terminal domain is required for nuclear localization in
      Xenopus XL2 cells in interphase. In human cells, however, we found both AurA and
      AurB kinases in the nucleus, AurA being mainly cytoplasmic and AurB mainly
      nuclear. Both proteins are actively excluded from the nucleus by a CRM1 dependent
      pathway. Interestingly, at a functional level, in interphase, every combination
      of Aurora kinase domains (ND-CD) rescues histone H3 Serine10 phosphorylation
      defect induced by AurB knockdown. This clearly indicates the presence of a
      functional AurA in the nucleus. However, the chimera ND-AurA/CD-AurB was much
      more efficient than the ND-AurB/ CD-AurA to rescue multinucleation also induced
      by AurB knockdown. This indicates that the catalytic domain of AurB is required
      to fulfill specific functions during mitosis that cannot be fulfilled by the
      catalytic domain of AurA, probably for localization reasons during mitosis.

PMID- 18802403
TI  - Mdm2 exerts pro-apoptotic activities by antagonizing insulin-like growth factor-I
      mediated survival.
AB  - The Mdm2 oncoprotein is an E3 ubiquitin ligase required to maintain the p53
      protein at low levels in embryonic and adult tissues. It also contributes to
      tumor formation by antagonizing p53 tumor suppressor activity when amplified
      and/or overexpressed. p53-independent role for Mdm2 has been suggested by
      transfection studies. Among the growing list of putative Mdm2-regulated proteins
      are several proteins playing a key role in the control of cell proliferation such
      as pRb, E2F1/DP1, Numb, Smads, Lats2 or IGF-1R. Consistent with the ability of
      Mdm2 to promote ubiquitylation and proteasome destruction of IGFR-I independently
      of p53, we show herein that loss of Mdm2 leads to a significant increase in IGF1
      R-beta protein levels both in cells lacking or expressing p53. Interestingly, IGF
      1 protects cells from DNA-damage-induced apoptosis only in absence of Mdm2. These
      data therefore further highlight a physiological role for Mdm2 in the control of
      IGF1 signalling and provide genetic evidence for a p53-independent proapoptotic
      function of Mdm2.

PMID- 18802404
TI  - Monitoring the rate of hospitalization before rotavirus immunization in Italy
      utilizing ICD9-CM regional databases.
AB  - BACKGROUND: Recently, two Rotavirus (RV) vaccines were licensed in Italy,
      rendering RV illness a vaccine preventable disease. To assess the RV
      hospitalization rate in Italy, a study focused on the Regional hospital discharge
      forms (HDD) databases was carried out. RESULTS: Regional HDD databases from
      Piemonte, Veneto, Friuli-Venezia-Giulia and Marche were analyzed. A total of
      434,335 hospitalizations were counted in the study timeframe and 13,234 VE
      diagnoses (3% of hospitalizations) were collected. A total of 8546 RVE cases (2%
      of hospitalizations, 64% of all VE) were observed, of which 1.2% were primary
      diagnoses (PD) and 0.8% secondary diagnosis (SD). The RVE hospitalization peak
      (4.9%) was observed at the age of 1 year (4.5% in 7-12 months of age) with a
      median hospital stay of 4.4 days (s.d +/- 4.2). Two deaths (out of 8546 RVE
      cases) were identified. PATIENTS AND METHODS: Regional HDD databases with the
      diagnosis of viral enteritis (VE) and RV enteritis (RVE) (ICD9-CM code 00861-69
      and 008.8) in any position of the first 20 discharge diagnoses in children aged
      less or equal to 5 years between 2001 and 2005 were requested. CONCLUSION:
      Despite some limitations due to the HDD synthetic contents and low potential for
      clinical interpretation, the Regional HDD databases, including PD and SD, may be
      a useful tool for monitoring the clinical impact of RV vaccination introduction
      in Italy.

PMID- 18802405
TI  - Speedy/Ringo C regulates S and G2 phase progression in human cells.
AB  - Cyclin-dependent kinases (CDKs) control cell cycle transitions and progression.
      In addition to their activation via binding to cyclins, CDKs can be activated via
      binding to an unrelated class of cell cycle regulators termed Speedy/Ringo (S/R)
      proteins. Although mammals contain at least five distinct Speedy/Ringo
      homologues, the specific functions of members of this growing family of CDK
      activators remain largely unknown. We investigated the cell cycle roles of human
      Speedy/Ringo C in HEK293 cells. Down-regulation of Speedy/Ringo C by RNA
      interference delayed S and G(2) progression whereas ectopic expression had the
      opposite effect, reducing S and G(2)/M populations. Double thymidine arrest and
      release experiments showed that overexpression of Speedy/Ringo C promoted late S
      phase progression. Using a novel three-color FACS protocol to determine the
      length of G(2) phase, we found that the suppression of Speedy/Ringo C by RNAi
      prolonged G(2) phase by approximately 30 min whereas ectopic expression of
      Speedy/Ringo C shortened G(2) phase by approximately 25 min. In addition,
      overexpression of Speedy/Ringo C disrupted the G(2) DNA damage checkpoint,
      increased cell death and caused a cell cycle delay at the G(1)-to-S transition.
      These observations indicate that CDK-Speedy/Ringo C complexes positively regulate
      cell cycle progression during the late S and G(2) phases of the cell cycle.

PMID- 18802406
TI  - Co-expression of fatty acid synthase and caveolin-1 in pancreatic ductal
      adenocarcinoma: implications for tumor progression and clinical outcome.
AB  - Pancreatic cancer is a devastating disease that afflicts over 35,000 Americans
      every year. Since therapeutic options are limited, understanding the molecular
      aspects of this disease is critical for moving towards targeted treatment of this
      aggressive form of cancer. Caveolin-1 (Cav-1) and fatty acid synthase (FASN) are
      two proteins that have been shown to be dysregulated in a number of cancers.
      Functionally these proteins have been shown to be involved in the process of
      tumorigenesis. We thus surveyed the expression of both these critical proteins in
      a series of pancreatic precancerous lesions (pancreatic intraepithelial
      neoplasia, PanIN) and pancreatic cancers. Cav-1 and FASN expression correlated
      predominantly with clinical characteristics, such as histologic grade and
      advanced tumor stage (e.g., high Cav-1 and FASN expression correlated with poor
      differentiation status) and a significant survival advantage was found in
      patients with low co-expressing FASN and Cav-1 tumors. Cav-1 and FASN expression
      was absent in PanIN lesions and the normal ducts and acini. Of note, Cav-1
      expression was detected in the fibroblasts of the desmoplastic pancreatic cancer
      stroma, but not in stromal cells of the normal pancreas. Mechanistically, these
      data support the notion that these proteins are co-regulated either directly or
      indirectly by another factor. Importantly, the co-expression of these proteins
      significantly correlates with clinical features and survival status of pancreatic
      cancer patients. Thus, Cav-1 and FASN may functionally cooperate in the process
      of pancreatic tumorigenesis, and as such, may be good candidate prognostic
      markers and targets for therapeutic intervention.

PMID- 18802407
TI  - Molecular insights into mechanisms regulating faithful chromosome separation in
      female meiosis.
AB  - The faithful segregation of chromosomes into daughter cells in meiosis is crucial
      to produce healthy progeny. In gametogenesis, two consecutive rounds of
      chromosome separation occur with only one round of DNA replication, and the
      chromosome number is reduced to half to produce haploid gametes. Here, we discuss
      the molecular mechanisms underlying faithful chromosome separation in meiosis
      from three aspects: spindle checkpoint, two-step releases of cohesion, and the
      specific space-time protection of cohesin.

PMID- 18802408
TI  - Phosphorylation of p53 on Ser15 during cell cycle caused by Topo I and Topo II
      inhibitors in relation to ATM and Chk2 activation.
AB  - The DNA topoisomerase I (topo1) inhibitor topotecan (TPT) and topo2 inhibitor
      mitoxantrone (MXT) damage DNA inducing formation of DNA double-strand breaks
      (DSBs). We have recently examined the kinetics of ATM and Chk2 activation as well
      as histone H2AX phosphorylation, the reporters of DNA damage, in individual human
      lung adenocarcinoma A549 cells treated with these drugs. Using a phospho-specific
      Ab to tumor suppressor protein p53 phosphorylated on Ser15 (p53-Ser15(P))
      combined with an Ab that detects p53 regardless of the phosphorylation status and
      multiparameter cytometry we correlated the TPT- and MXT-induced p53-Ser15(P) with
      ATM and Chk2 activation as well as with H2AX phosphorylation in relation to the
      cell cycle phase. In untreated interphase cells, p53-Ser15(P) had "patchy"
      localization throughout the nucleoplasm while mitotic cells showed strong p53
      Ser15(P) cytoplasmic immunofluorescence (IF). The intense phosphorylation of p53
      Ser15, combined with activation of ATM and Chk2 (involving centrioles) as well as
      phosphorylation of H2AX seen in the untreated mitotic cells, suggest mobilization
      of the DNA damage detection/repair machinery in controlling cytokinesis. In the
      nuclei of cells treated with TPT or MXT, the expression of p53-Ser15(P) appeared
      as closely packed foci of intense IF. Following TPT treatment, the induction of
      p53-Ser15(P) was most pronounced in S-phase cells while no significant cell cycle
      phase differences were seen in cells treated with MXT. The maximal increase in
      p53-Ser15(P) expression, rising up to 2.5-fold above the level of its
      constitutive expression, was observed in cells treated with TPT or MXT for 4-6 h.
      This maximum expression of p53-Ser15(P) coincided in time with the peak of Chk2
      activation but not with ATM activation and H2AX phosphorylation, both of which
      crested 1-2 h after the treatment with TPT or MXT. The respective kinetics of p53
      Ser15 phosphorylation versus ATM and Chk2 activation suggest that in response to
      DNA damage by TPT or MXT, Chk2 rather than ATM mediates p53 phosphorylation.

PMID- 18802409
TI  - Federal air travel restrictions for public health purposes--United States, June
      2007-May 2008.
AB  - Persons with communicable diseases who travel on commercial aircraft can pose a
      risk for infection to the traveling public. In June 2007, federal agencies
      developed a public health Do Not Board (DNB) list, enabling domestic and
      international public health officials to request that persons with communicable
      diseases who meet specific criteria and pose a serious threat to the public be
      restricted from boarding commercial aircraft departing from or arriving in the
      United States. The public health DNB list is managed by CDC and the U.S.
      Department of Homeland Security (DHS). To describe the experience with the public
      health DNB list since its inception, CDC analyzed data from June 2007 to May
      2008. This report summarizes the results of that analysis, which indicated that
      CDC received requests for inclusion of 42 persons on the public health DNB list,
      all with suspected or confirmed pulmonary tuberculosis (TB). From the requests,
      33 (79%) persons were included on the list. The public health DNB list enables
      public health officials to prevent travel on commercial aircraft by persons who
      pose a risk for infection to other travelers. State and local health departments
      in the United States and other countries should be aware of this new public
      health tool.

PMID- 18802410
TI  - Impact of expanded newborn screening--United States, 2006.
AB  - Universal newborn screening for selected metabolic, endocrine, hematologic, and
      functional disorders is a well-established practice of state public health
      programs. Recent developments in tandem mass spectrometry (MS/MS), which is now
      capable of multi-analyte analysis in a high throughput capacity, has enabled
      newborn screening to include many more disorders detectable from a newborn blood
      spot. In 2006, to address the substantial variation that existed from state to
      state in the number of disorders included in newborn screening panels, the
      American College of Medical Genetics (ACMG), under guidance from the Health
      Resources and Services Administration, recommended a uniform panel of 29
      disorders, which was subsequently endorsed by the federal Advisory Committee on
      Heritable Disorders in Newborns and Children. After 2006, most states began to
      expand their panels to include all 29 disorders; currently, 21 states and the
      District of Columbia have fully implemented the ACMG panel. To estimate the
      burden to state newborn screening programs resulting from this expansion, CDC
      used 2001-2006 data from those states with well-established MS/MS screening
      programs to estimate the number of children in the United States who would have
      been identified with disorders in 2006 if all 50 states and the District of
      Columbia had been using the ACMG panel. This report describes the results of that
      analysis, which indicated that, although such an expansion would have increased
      the number of children identified by only 32% (from 4,370 to 6,439), these
      children would have had many rare disorders that require local or regional
      capacity to deliver expertise in screening, diagnosis, and management. The
      findings underscore the need for public health and health-care delivery systems
      to build or expand the programs required to manage the rare disorders detected
      through expanded newborn screening, while also continuing programs to address
      more common disorders.

PMID- 18802411
TI  - Thallium poisoning from eating contaminated cake--Iraq, 2008.
AB  - Thallium is an odorless, tasteless, heavy metal formerly used in rodenticides and
      still used in some manufacturing processes (e.g., electronics, pharmaceuticals,
      and glass). Thallium also has been used for intentional poisonings. Acute
      thallium poisoning produces gastrointestinal symptoms and signs, such as vomiting
      and acute abdominal pain, in the first few hours after ingestion, and initially
      is indistinguishable from other causes of acute gastrointestinal toxicity.
      However, within several days of ingestion, acute thallium poisoning often
      produces neurologic symptoms, such as extreme pain and acute muscle weakness
      ascending from the lower extremities, consistent with heavy metal toxicity. On
      January 22, 2008, 10 of 12 members in two families in Baghdad, Iraq, developed
      gastrointestinal symptoms; four of those 10 persons subsequently died from acute
      thallium poisoning, and five developed neurologic symptoms but survived. The
      Jordan Field Epidemiology Training Program investigated this cluster at the
      request of the World Health Organization (WHO) representative in Iraq. The
      preliminary investigation indicated this was an intentional poisoning, and law
      enforcement officials began a criminal investigation. Physicians who see the
      sudden onset of painful peripheral neuropathy and hair loss in patients should
      consider the possibility of thallium poisoning.

PMID- 18802412
TI  - Recommendations for identification and public health management of persons with
      chronic hepatitis B virus infection.
AB  - Serologic testing for hepatitis B surface antigen (HBsAg) is the primary way to
      identify persons with chronic hepatitis B virus (HBV) infection. Testing has been
      recommended previously for pregnant women, infants born to HBsAg-positive
      mothers, household contacts and sex partners of HBV-infected persons, persons
      born in countries with HBsAg prevalence of >/=8%, persons who are the source of
      blood or body fluid exposures that might warrant postexposure prophylaxis (e.g.,
      needlestick injury to a health-care worker or sexual assault), and persons
      infected with human immunodeficiency virus. This report updates and expands
      previous CDC guidelines for HBsAg testing and includes new recommendations for
      public health evaluation and management for chronically infected persons and
      their contacts. Routine testing for HBsAg now is recommended for additional
      populations with HBsAg prevalence of >/=2%: persons born in geographic regions
      with HBsAg prevalence of >/=2%, men who have sex with men, and injection-drug
      users. Implementation of these recommendations will require expertise and
      resources to integrate HBsAg screening in prevention and care settings serving
      populations recommended for HBsAg testing. This report is intended to serve as a
      resource for public health officials, organizations, and health-care
      professionals involved in the development, delivery, and evaluation of prevention
      and clinical services.

PMID- 18802413
TI  - Genetic and genomic analyses of the division of labour in insect societies.
AB  - Division of labour--individuals specializing in different activities--features
      prominently in the spectacular success of the social insects. Until recently,
      genetic and genomic analyses of division of labour were limited to just a few
      species. However, research on an ever-increasing number of species has provided
      new insight, from which we highlight two results. First, heritable influences on
      division of labour are more pervasive than previously imagined. Second, different
      forms of division of labour, in lineages in which eusociality has arisen
      independently, have evolved through changes in the regulation of highly conserved
      molecular pathways associated with several basic life-history traits, including
      nutrition, metabolism and reproduction.

PMID- 18802416
TI  - Universal health care, genomic medicine and Thailand: investing in today and
      tomorrow.
AB  - One potential outcome of investing in genomic medicine is the provision of tools
      for creating a more cost-effective health-care system. Partly with this aim in
      mind, Thailand has launched two genotyping initiatives: the Thai SNP Discovery
      Project and the Thai Centre for Excellence in Life Sciences Pharmacogenomics
      Project. Together, these projects will help Thailand understand the genomic
      diversity of its population and explore the role that this diversity has in drug
      response and disease susceptibility in its population. A major future challenge
      will be for Thailand to integrate genomic medicine in its relatively young
      universal health-care system.

PMID- 18802414
TI  - Explaining human uniqueness: genome interactions with environment, behaviour and
      culture.
AB  - What makes us human? Specialists in each discipline respond through the lens of
      their own expertise. In fact, 'anthropogeny' (explaining the origin of humans)
      requires a transdisciplinary approach that eschews such barriers. Here we take a
      genomic and genetic perspective towards molecular variation, explore systems
      analysis of gene expression and discuss an organ-systems approach. Rejecting any
      'genes versus environment' dichotomy, we then consider genome interactions with
      environment, behaviour and culture, finally speculating that aspects of human
      uniqueness arose because of a primate evolutionary trend towards increasing and
      irreversible dependence on learned behaviours and culture - perhaps relaxing
      allowable thresholds for large-scale genomic diversity.

PMID- 18802415
TI  - The genetics of mammalian circadian order and disorder: implications for
      physiology and disease.
AB  - Circadian cycles affect a variety of physiological processes, and disruptions of
      normal circadian biology therefore have the potential to influence a range of
      disease-related pathways. The genetic basis of circadian rhythms is well studied
      in model organisms and, more recently, studies of the genetic basis of circadian
      disorders has confirmed the conservation of key players in circadian biology from
      invertebrates to humans. In addition, important advances have been made in
      understanding how these molecules influence physiological functions in tissues
      throughout the body. Together, these studies set the scene for applying our
      knowledge of circadian biology to the understanding and treatment of a range of
      human diseases, including cancer and metabolic and behavioural disorders.

PMID- 18802417
TI  - South Africa: from species cradle to genomic applications.
AB  - The South African government is committed to science and technology innovation,
      to establishing a knowledge-based economy and to harnessing life-sciences
      research for health and economic development. Given the constraints and the early
      stage of development of the field as a whole in South Africa, we found an
      impressive amount of research on human genomic variation in this country.
      Encouragingly, South Africa is beginning to apply genomics to address local
      health needs, including HIV and tuberculosis (TB) infections. We document a
      number of initiatives in South Africa that are beginning to study genetic
      variation within the various local indigenous populations. Other early
      initiatives focus on pharmacogenetic studies, mutation characterization in
      individual disease genes and genome-wide association studies. Public engagement
      in genomic issues is spear-headed by The Africa Genome Education Institute.

PMID- 18802418
TI  - The next steps for genomic medicine: challenges and opportunities for the
      developing world.
AB  - This is a historical moment on the path to genomic medicine - the point at which
      theory is about to be translated into practice. We have previously described
      human genome variation studies taking place in Mexico, India, Thailand, and South
      Africa. Such investments into science and technology will enable these countries
      to embark on the path to the medical and health applications of genomics, and to
      benefit economically. Here we provide a perspective on the challenges and
      opportunities facing these and other countries in the developing world as they
      begin to harness genomics for the benefit of their populations.

PMID- 18802419
TI  - Genomics, public health and developing countries: the case of the Mexican
      National Institute of Genomic Medicine (INMEGEN).
AB  - In 2004, the government of Mexico established the National Institute of Genomic
      Medicine (INMEGEN), to carry out disease-related genomic studies that will
      address national health problems and stimulate scientific and technological
      development by generating new commercial products and services in genomic
      medicine. Towards this end, INMEGEN is carrying out a large-scale genotyping
      project to map genomic variation within its own population. The initiative is
      expected to generate a key resource for local researchers to understand disease
      susceptibility and variation in drug responses, which will contribute to Mexico's
      goal of developing public health genomics - a field in which Mexico is proving to
      be a leader amongst emerging economies.

PMID- 18802420
TI  - From diversity to delivery: the case of the Indian Genome Variation initiative.
AB  - India currently has the world's second-largest population along with a fast
      growing economy and significant economic disparity. It also continues to
      experience a high rate of infectious disease and increasingly higher rates of
      chronic diseases. However, India cannot afford to import expensive technologies
      and therapeutics nor can it, as an emerging economy, emulate the health-delivery
      systems of the developed world. Instead, to address these challenges it is
      looking to biotechnology-based innovation in the field of genomics. The Indian
      Genome Variation (IGV) consortium, a government-funded collaborative network
      among seven local institutions, is a reflection of these efforts. The IGV has
      recently developed the first large-scale database of genomic diversity in the
      Indian population that will facilitate research on disease predisposition,
      adverse drug reactions and population migration.

PMID- 18802422
TI  - Imaging as a biomarker for therapy response: cancer as a prototype for the
      creation of research resources.

PMID- 18802425
TI  - Imaging guiding therapy development in lymphoma.
AB  - Radiographic imaging has deep roots as a surrogate for efficacy in guiding
      decisions in therapy development in lymphoma. Nodal lymphomas are generally easy
      to measure in two dimensions and frequently shrink promptly when exposed to
      therapies that result in long-term clinical usefulness. New therapies in lymphoma
      are still required to induce radiographic response to be considered useful in a
      paradigm dating back at least to chest roentgenograms and Hodgkin's lymphoma
      (HL). This paradigm will soon be challenged by new therapeutic strategies under
      development, but creative imaging approaches can still guide such development.

PMID- 18802426
TI  - The Pharm.D. investigator in clinical pharmacology: supply and demand.

PMID- 18802427
TI  - Serum uric acid levels correlate with plasma hydrogen peroxide and protein
      carbonyl levels in preeclampsia.
AB  - BACKGROUND: Increased serum uric acid has been postulated to directly promote
      oxidative stress. The aim of this study was to investigate whether serum uric
      acid level correlated with superoxide generation and oxidative stress in
      preeclampsia. METHODS: We assessed serum uric acid levels, plasma hydrogen
      peroxide levels, and plasma protein carbonyl levels in normal pregnant (n = 14)
      and preeclamptic women (n = 17). Serum uric acid and plasma hydrogen peroxide
      levels were determined by the uricase-peroxidase method, a combined enzymatic
      colorimetric method. Plasma carbonyl levels were measured by ELISA. RESULTS: The
      mean serum uric acid values were significantly elevated in preeclampsia (6.6 +/-
      1.5 mg/dl) compared with normal pregnancy (4.0 +/- 0.7 mg/dl) (P < 0.001). Plasma
      protein carbonyl levels were also significantly elevated in preeclampsia (7.72 +/
      4.10 nmol/mg) compared with normal pregnancy (2.85 +/- 3.06 nmol/mg) (P =
      0.0011). In addition, the plasma hydrogen peroxide levels were significantly
      higher in preeclampsia (66.9 +/- 10.9 micromol/l) compared with normal pregnancy
      (50.1 +/- 5.6 micromol/l) (P < 0.001). Serum uric acid levels correlated
      significantly and positively with plasma hydrogen peroxide levels (r(2) = 0.2965,
      P = 0.0027) and plasma protein carbonyl levels (r(2) = 0.2011, P = 0.0129).
      CONCLUSION: The increased serum uric acid levels correlated closely with plasma
      hydrogen peroxide levels and plasma protein carbonyl levels in preeclampsia.
      Therefore, the serum uric acid level serves as an indicator of the underlying
      oxidative stress in preeclampsia.

PMID- 18802428
TI  - Large artery stiffening as a link between cerebral lacunar infarction and renal
      albuminuria.
AB  - BACKGROUND: Stiffening of large arteries increases pulsatile pressure and flow
      stresses, which extend to the microcirculation in vasodilated organs such as the
      brain and kidneys. Subclinical cerebral lacunar infarction and albuminuria, both
      of which are early manifestations of microvascular damage, have been shown to be
      potentially interrelated in hypertension and with aging, but the underlying
      pathogenesis remains unknown. METHODS: In a population of 351 general adults aged
      > or =50 years, urinary albumin/creatinine ratio (ACR), pulse wave velocity
      (PWV), and 24-h ambulatory blood pressure (BP) were measured, and cerebral
      lacunar lesions were assessed on magnetic resonance imaging (MRI). RESULTS:
      Lacunar infarction was present in 86 subjects (25%). Subjects with lacunae had a
      higher median urinary ACR than those without (20.6 vs. 14.6 mg/g.Cr, P = 0.004).
      The positive association between the presence of lacunae and urinary ACR remained
      significant in a logistic model that adjusted for covariates including age,
      gender, and 24-h BP (P = 0.04); the odds ratio (OR) for lacunae was 1.32 for each
      1 s.d. increase in urinary ACR. However, when PWV was added to this model,
      increased PWV but not urinary ACR was associated with lacunae. There was a
      significant interaction between urinary ACR and PWV with respect to lacunae; only
      subjects with a high PWV above the median showed an independent association
      between urinary ACR and the presence of lacunae (P = 0.03). CONCLUSIONS:
      Microvascular damage in the brain (lacunar infarction) and kidney (albuminuria)
      appears to be interrelated in the general population. Large arterial stiffening
      may play a pivotal role in this cerebro-renal connection.

PMID- 18802429
TI  - Abnormal glucose metabolism in hypertensive mice with genetically interrupted
      gamma-melanocyte stimulating hormone signaling fed a high-sodium diet.
AB  - BACKGROUND: Rodents with deficiency of or resistance to the proopiomelanocortin
      derived peptide gamma-melanocyte stimulating hormone (gamma-MSH) develop marked
      salt-sensitive hypertension. We asked whether this hypertension was accompanied
      by abnormal glucose metabolism. METHODS: gamma-MSH-deficient Pc2(-/-) mice, and
      resistant Mc3r(-/-) mice were studied acutely for measurement of blood pressure
      and glucose and insulin concentrations after > or =1 week of a high-sodium diet
      (HSD; 8% NaCl) compared to a normal-sodium diet (NSD; 0.4% NaCl). Mc3r(-/-) also
      underwent glucose tolerance test (GTT) and insulin tolerance test. RESULTS: Both
      knockout strains were hypertensive and also exhibited fasting hyperglycemia and
      hyperinsulinemia on the HSD. Mc3r(-/-) mice on the HSD had impaired glucose
      tolerance and insulin-mediated glucose disposal compared to wild-type mice on
      either the HSD or the NSD, or to Mc3r(-/-) mice on the NSD. CONCLUSIONS: These
      results indicate an interaction of interrupted gamma-MSH signaling with the HSD
      to cause hypertension on the one hand and abnormal glucose metabolism, with the
      characteristics of insulin resistance, on the other. Further study of the nature
      of this interaction should provide new insight into the mechanisms by which salt
      sensitive hypertension and insulin resistance are linked.

PMID- 18802430
TI  - Association between pulse pressure and 30-month all-cause mortality in peritoneal
      dialysis patients.
AB  - BACKGROUND: Pulse pressure (PP) is an independent predictor of cardiovascular
      and/or all-cause mortality in patients with underlying cardiovascular disease. We
      examined whether PP can be used to predict overall mortality in peritoneal
      dialysis (PD) patients. METHODS: We studied 153 PD patients (mean age, 54.5 +/-
      14.2 years) with end-stage renal disease. PP was measured monthly for 3 months.
      At the time of the third PP measurement, baseline demographic, clinical,
      biochemical, and dialysis data were collected. Patients were stratified into
      tertiles according to average PP, and the relationship between blood pressure
      parameters and all-cause mortality over a 30-month follow-up was assessed using
      Cox regression. RESULTS: There were 27 deaths; three deaths occurred after the
      change to hemodialysis (HD) (subjects died within 3 months after HD) and were
      counted as events during survival analysis. The overall 30-month survival (Kaplan
      Meier curves) times were significantly different among the tertiles of PP (P <
      0.05). Increased PP was significantly associated with overall mortality
      regardless of adjustment for systolic blood pressure (SBP) or diastolic blood
      pressure (DBP). CONCLUSIONS: PP may be the most consistent blood pressure
      indicator of mortality risk. All-cause mortality events in PD patients are more
      related to pulsatile stress caused by the stiffness of large arteries during
      systole (reflected in a rise of PP) than to steady-state stress stemming from
      resistance during diastole (reflected in a rise of SBP and DBP).

PMID- 18802431
TI  - Hypertension due to a renin-secreting juxtaglomerular cell tumor.

PMID- 18802432
TI  - Pulse pressure and adverse outcomes in women: a report from the Women's Ischemia
      Syndrome Evaluation (WISE).
AB  - BACKGROUND: Recent data suggest that brachial pulse pressure (PP) may be a better
      predictor of outcome than systolic or diastolic blood pressure (SBP/DBP). We
      sought to investigate the relative contributions of these indices to risk for
      adverse outcomes in women with suspected coronary artery disease (CAD) and
      myocardial ischemia. METHODS: Among 857 women referred for angiography for
      suspected myocardial ischemia, baseline evaluations were performed, and the women
      were followed for clinical outcome. Relationships between baseline
      characteristics, blood pressure components, and outcomes were evaluated. Separate
      multivariate stepwise Cox regression models for PP and SBP (expressed in 10 mm Hg
      increments) were constructed and included covariates significantly associated
      with adverse outcomes. RESULTS: After 5.2 years (mean), univariate testing
      identified higher PP associated with higher risk for cardiovascular (CV)
      mortality and adverse CV outcomes than SBP, DBP, or mean arterial pressure (MAP).
      Multivariate modeling identified both PP and SBP associated with adverse CV
      outcomes, but only PP was significantly associated with higher CV mortality. When
      both PP and SBP were included in the model, only PP remained an independent
      predictor of adverse outcomes for CV events. CONCLUSIONS: In women with suspected
      CAD and myocardial ischemia, PP is a stronger predictor of adverse outcomes than
      SBP, DBP, or MAP with an 18% excess mortality risk for every 10 mm Hg increase in
      PP. Further investigations into pathophysiologic mechanisms and specific
      pharmacologic approaches to modifying this novel target are warranted.

PMID- 18802433
TI  - Association of lactate with blood pressure before and after rapid weight loss.
AB  - BACKGROUND: The mechanism linking obesity with its downstream complications is
      poorly understood. Accumulating evidence suggests that insufficient oxidative
      capacity plays a central role in the development of insulin resistance and,
      perhaps, hypertension. METHODS: To investigate this hypothesis, we measured
      lactate, a marker of the gap between energy expenditure and oxidative capacity,
      in 40 obese subjects with the metabolic syndrome (Ob-MS), 40 obese subjects
      without the metabolic syndrome (Ob), and 20 lean controls (LCs). The 40 Ob-MS
      participants were then entered into a 12-20 week very low-calorie diet (VLCD)
      intervention. The change in lactate and a number of other metabolic factors
      including blood pressure were subsequently assessed. RESULTS: At baseline, median
      lactate levels were significantly higher in both the Ob (36.4 mg/dl) and Ob-MS
      (34.7 mg/dl) groups when compared to LCs (17.4 mg/dl; P < 0.001). After the VLCD
      intervention, Ob-MS subjects lost 14.7 kg on average, corresponding to a 5.0
      kg/m(2) decrease in body mass index (BMI). Lactate levels fell from 41.3 to 28.7
      mg/dl, a 31% reduction (P = 0.006). Even after adjustment for BMI change, change
      in lactate was strongly associated with change in diastolic blood pressure (DBP)
      (P = 0.007) and mean arterial pressure (P = 0.014), but not with systolic blood
      pressure (SBP) (P = 0.20) or other obesity-related traits. CONCLUSIONS: Baseline
      and longitudinal associations between lactate and DBP suggest that insufficient
      oxidative capacity may play a role in obesity-related hypertension.

PMID- 18802434
TI  - Aliskiren fails to lower blood pressure in patients who have either low PRA
      levels or whose PRA falls insufficiently or reactively rises.
AB  - BACKGROUND: Suppressed baseline plasma renin activity (PRA) levels or large
      reactive increases in renin secretion are two possible reasons for treatment
      failure with antirenin system drugs. METHODS: To investigate their prevalence we
      reanalyzed data from three published clinical trials of the renin inhibitor
      aliskiren. RESULTS: Aliskiren failed to lower systolic blood pressure (SBP) by at
      least 10 mm Hg in half of all patients. It was very effective in two-thirds of
      medium- to high-renin patients (-19 mm Hg). But BP did not fall in most low-renin
      patients, or in 30% of medium- to high-renin patients. BP actually rose by >10 mm
      Hg in 5% of patients taking aliskiren and in >10% of patients when aliskiren was
      added to an angiotensin receptor blocker (ARB) or angiotensin converting enzyme
      inhibitor (ACEI). PRA changed in parallel with BP. Although PRA fell in most
      patients, it actually rose in 5% and in up to 30% when aliskiren was added to an
      ARB or ACEI. CONCLUSIONS: There are two reasons for treatment failure with
      aliskiren. Many hypertensive patients have large BP falls. But, BP does not fall
      in most low-renin patients or in medium- to high-renin patients whose PRA levels
      do not fall sufficiently. If the concept of that treatment resistance is caused
      by excessive reactive increases in renin secretion is confirmed, then a PRA
      determination during treatment could be used to guide subsequent addition or
      subtraction of either natriuretic or antirenin drug types, to thereby correct BP
      and reduce cardiovascular risk.

PMID- 18802436
TI  - A protocol for removal of antibiotic resistance cassettes from human embryonic
      stem cells genetically modified by homologous recombination or transgenesis.
AB  - The first step in the generation of genetically tagged human embryonic stem cell
      (HESC) reporter lines is the isolation of cells that contain a stably integrated
      copy of the reporter vector. These cells are identified by their continued growth
      in the presence of a specific selective agent, usually conferred by a cassette
      encoding antibiotic resistance. In order to mitigate potential interference
      between the regulatory elements driving expression of the antibiotic resistance
      gene and those controlling the reporter gene, it is advisable to remove the
      positive selection cassette once the desired clones have been identified. This
      report describes a protocol for the removal of loxP-flanked selection cassettes
      from genetically modified HESCs by transient transfection with a vector
      expressing Cre recombinase. An integrated procedure for the clonal isolation of
      these genetically modified lines using single-cell deposition flow cytometry is
      also detailed. When performed sequentially, these protocols take approximately 1
      month.

PMID- 18802435
TI  - Design and delivery of antisense oligonucleotides to block microRNA function in
      cultured Drosophila and human cells.
AB  - MicroRNAs (miRNAs), approximately 22-nt RNAs that mediate post-transcriptional
      regulation of mRNAs in animals and plants, are a diverse class of regulatory
      genes whose specific biological functions are largely unknown. Here we detail a
      protocol to design and introduce into cultured Drosophila and human cells
      sequence-specific antisense oligonucleotides (ASOs) that block the function of
      individual miRNAs. Coupled with recent studies that catalog the miRNAs expressed
      in diverse cultured cells, our method offers a rapid (<1 week) approach to
      validate miRNA targets and to study the cellular functions of individual human
      and Drosophila miRNAs. ASO-based inactivation of miRNAs is faster and simpler
      than comparable genetic or 'sponge'-based approaches, for which extensive
      recombinant DNA manipulation is required. We present our ASO design principles
      and an optimized transfection protocol in which transfection efficiency of
      Drosophila Schneider 2 cells can approach 100%. Our 3'-cholesterol-modified ASOs
      have enhanced potency, allowing miRNA inhibition for at least 7 d from a single
      transfection.

PMID- 18802437
TI  - Paired-recordings from synaptically coupled cortical and hippocampal neurons in
      acute and cultured brain slices.
AB  - Analysis of synaptic transmission, synaptic plasticity, axonal processing,
      synaptic timing or electrical coupling requires the simultaneous recording of
      both the pre- and postsynaptic compartments. Paired-recording technique of
      monosynaptically connected neurons is also an appropriate technique to probe the
      function of small molecules (calcium buffers, peptides or small proteins) at
      presynaptic terminals that are too small to allow direct whole-cell patch-clamp
      recording. We describe here a protocol for obtaining, in acute and cultured
      slices, synaptically connected pairs of cortical and hippocampal neurons, with a
      reasonably high probability. The protocol includes four main stages
      (acute/cultured slice preparation, visualization, recording and analysis) and can
      be completed in approximately 4 h.

PMID- 18802438
TI  - 'Calling Cards' method for high-throughput identification of targets of yeast DNA
      binding proteins.
AB  - We present a protocol for a novel method for identifying the targets of DNA
      binding proteins in the genome of the yeast Saccharomyces cerevisiae. This is
      accomplished by engineering a DNA-binding protein so that it leaves behind in the
      genome a permanent mark -- a 'calling card' -- that provides a record of that
      protein's visit to that region of the genome. The calling card is the yeast Ty5
      retrotransposon, whose integrase interacts with the Sir4 protein. If Sir4 is
      fused to a DNA-binding protein, it recruits the Ty5 integrase, which directs
      insertion of a Ty5 calling card into the genome. The calling card along with the
      flanking genomic DNA is harvested by inverse PCR and its genomic location is
      determined by hybridization of the product to a DNA microarray. This method
      provides a straightforward alternative to the 'ChIP-chip' method for determining
      the targets of DNA-binding proteins. This protocol takes approximately 2 weeks to
      complete.

PMID- 18802439
TI  - Using RSAT to scan genome sequences for transcription factor binding sites and
      cis-regulatory modules.
AB  - This protocol shows how to detect putative cis-regulatory elements and regions
      enriched in such elements with the regulatory sequence analysis tools (RSAT) web
      server (http://rsat.ulb.ac.be/rsat/). The approach applies to known transcription
      factors, whose binding specificity is represented by position-specific scoring
      matrices, using the program matrix-scan. The detection of individual binding
      sites is known to return many false predictions. However, results can be strongly
      improved by estimating P value, and by searching for combinations of sites
      (homotypic and heterotypic models). We illustrate the detection of sites and
      enriched regions with a study case, the upstream sequence of the Drosophila
      melanogaster gene even-skipped. This protocol is also tested on random control
      sequences to evaluate the reliability of the predictions. Each task requires a
      few minutes of computation time on the server. The complete protocol can be
      executed in about one hour.

PMID- 18802440
TI  - Using RSAT oligo-analysis and dyad-analysis tools to discover regulatory signals
      in nucleic sequences.
AB  - This protocol explains how to discover functional signals in genomic sequences by
      detecting over- or under-represented oligonucleotides (words) or spaced pairs
      thereof (dyads) with the Regulatory Sequence Analysis Tools
      (http://rsat.ulb.ac.be/rsat/). Two typical applications are presented: (i)
      predicting transcription factor-binding motifs in promoters of coregulated genes
      and (ii) discovering phylogenetic footprints in promoters of orthologous genes.
      The steps of this protocol include purging genomic sequences to discard redundant
      fragments, discovering over-represented patterns and assembling them to obtain
      degenerate motifs, scanning sequences and drawing feature maps. The main strength
      of the method is its statistical ground: the binomial significance provides an
      efficient control on the rate of false positives. In contrast with optimization
      based pattern discovery algorithms, the method supports the detection of under-
      as well as over-represented motifs. Computation times vary from seconds (gene
      clusters) to minutes (whole genomes). The execution of the whole protocol should
      take approximately 1 h.

PMID- 18802441
TI  - Analyzing multiple data sets by interconnecting RSAT programs via SOAP Web
      services: an example with ChIP-chip data.
AB  - This protocol shows how to access the Regulatory Sequence Analysis Tools (RSAT)
      via a programmatic interface in order to automate the analysis of multiple data
      sets. We describe the steps for writing a Perl client that connects to the RSAT
      Web services and implements a workflow to discover putative cis-acting elements
      in promoters of gene clusters. In the presented example, we apply this workflow
      to lists of transcription factor target genes resulting from ChIP-chip
      experiments. For each factor, the protocol predicts the binding motifs by
      detecting significantly overrepresented hexanucleotides in the target promoters
      and generates a feature map that displays the positions of putative binding sites
      along the promoter sequences. This protocol is addressed to bioinformaticians and
      biologists with programming skills (notions of Perl). Running time is
      approximately 6 min on the example data set.

PMID- 18802442
TI  - Network Analysis Tools: from biological networks to clusters and pathways.
AB  - Network Analysis Tools (NeAT) is a suite of computer tools that integrate various
      algorithms for the analysis of biological networks: comparison between graphs,
      between clusters, or between graphs and clusters; network randomization; analysis
      of degree distribution; network-based clustering and path finding. The tools are
      interconnected to enable a stepwise analysis of the network through a complete
      analytical workflow. In this protocol, we present a typical case of utilization,
      where the tasks above are combined to decipher a protein-protein interaction
      network retrieved from the STRING database. The results returned by NeAT are
      typically subnetworks, networks enriched with additional information (i.e.,
      clusters or paths) or tables displaying statistics. Typical networks comprising
      several thousands of nodes and arcs can be analyzed within a few minutes. The
      complete protocol can be read and executed in approximately 1 h.

PMID- 18802443
TI  - Lineage fate and intense debate: myths, models and mechanisms of CD4- versus CD8
      lineage choice.
AB  - Following successful gene rearrangement at alphabeta T-cell receptor (TCR) loci,
      developing thymocytes express both CD4 and CD8 co-receptors and undergo a life-or
      death selection event, which is known as positive selection, to identify cells
      that express TCRs with potentially useful ligand specificities. Positively
      selected thymocytes must then differentiate into either CD4(+) helper T cells or
      CD8(+) cytotoxic T cells, a crucial decision known as CD4/CD8-lineage choice. In
      this Review, we summarize recent advances in our understanding of the cellular
      and molecular events involved in lineage-fate decision and discuss them in the
      context of the major models of CD4/CD8-lineage choice.

PMID- 18802444
TI  - Harmful molecular mechanisms in sepsis.
AB  - Sepsis and sepsis-associated multi-organ failure are major challenges for
      scientists and clinicians and are a tremendous burden for health-care systems.
      Despite extensive basic research and clinical studies, the pathophysiology of
      sepsis is still poorly understood. We are now beginning to understand that sepsis
      is a heterogeneous, dynamic syndrome caused by imbalances in the 'inflammatory
      network'. In this Review, we highlight recent insights into the molecular
      interactions that occur during sepsis and attempt to unravel the nature of the
      dysregulated immune response during sepsis.

PMID- 18802445
TI  - CART peptides: regulators of body weight, reward and other functions.
AB  - Over the past decade or so, CART (cocaine- and amphetamine-regulated transcript)
      peptides have emerged as major neurotransmitters and hormones. CART peptides are
      widely distributed in the CNS and are involved in regulating many processes,
      including food intake and the maintenance of body weight, reward and endocrine
      functions. Recent studies have produced a wealth of information about the
      location, regulation, processing and functions of CART peptides, but additional
      studies aimed at elucidating the physiological effects of the peptides and at
      characterizing the CART receptor(s) are needed to take advantage of possible
      therapeutic applications.

PMID- 18802446
TI  - Thirty years of Alzheimer's disease genetics: the implications of systematic meta
      analyses.
AB  - The genetic underpinnings of Alzheimer's disease (AD) remain largely elusive
      despite early successes in identifying three genes that cause early-onset
      familial AD (those that encode amyloid precursor protein (APP) and the
      presenilins (PSEN1 and PSEN2)), and one genetic risk factor for late-onset AD
      (the gene that encodes apolipoprotein E (APOE)). A large number of studies that
      aimed to help uncover the remaining disease-related loci have been published in
      recent decades, collectively proposing or refuting the involvement of over 500
      different gene candidates. Systematic meta-analyses of these studies currently
      highlight more than 20 loci that have modest but significant effects on AD risk.
      This Review discusses the putative pathogenetic roles and common biochemical
      pathways of some of the most genetically and biologically compelling of these
      potential AD risk factors.

PMID- 18802447
TI  - Function and regulation of protein neddylation. 'Protein modifications: beyond
      the usual suspects' review series.
AB  - Neddylation is the post-translational protein modification that is most closely
      related to ubiquitination. However, ubiquitination is known to regulate a myriad
      of processes in eukaryotic cells, whereas only a limited number of neddylation
      substrates have been described to date. Here, we review the principles of protein
      neddylation and highlight the mechanisms that ensure the specificity of
      neddylation over ubiquitination. As numerous neddylation substrates probably
      remain to be discovered, we propose some criteria that could be used as
      guidelines for the characterization of neddylated proteins.

PMID- 18802448
TI  - Science's twin taboos. Is it premature to declare that the debates about the role
      of religion and race in science are closed?

PMID- 18802449
TI  - Plasticity of Drosophila Stat DNA binding shows an evolutionary basis for Stat
      transcription factor preferences.
AB  - In vertebrates, seven signal transducer and activator of transcription (STAT)
      proteins bind to palindromic sites separated by spacers of two or three
      nucleotides (STAT1), four nucleotides (STAT6) or three nucleotides (STAT2 to
      STAT5a/b). This diversity of binding sites provides specificity to counter
      semiredundancy and was thought to be a recent evolutionary acquisition. Here, we
      examine the natural DNA-binding sites of the single Drosophila Stat and show that
      this is not the case. Rather, Drosophila Stat92E is able to bind to and activate
      target gene expression through both 3n and 4n spaced sites. Our experiments
      indicate that Stat92E has a higher binding affinity for 3n sites than for 4n
      sites and suggest that the levels of target gene expression can be modulated by
      insertion and/or deletion of single bases. Our results indicate that the
      ancestral STAT protein had the capacity to bind to 3n and 4n sites and that
      specific STAT binding preferences evolved with the radiation of the vertebrate
      STAT family.

PMID- 18802450
TI  - Processive kinesins require loose mechanical coupling for efficient collective
      motility.
AB  - Processive motor proteins are stochastic steppers that perform actual mechanical
      steps for only a minor fraction of the time they are bound to the filament track.
      Motors usually work in teams and therefore the question arises whether the
      stochasticity of stepping can cause mutual interference when motors are
      mechanically coupled. We used biocompatible surfaces to immobilize processive
      kinesin-1 motors at controlled surface densities in a mechanically well-defined
      way. This helped us to study quantitatively how mechanical coupling between
      motors affects the efficiency of collective microtubule transport. We found that
      kinesin-1 constructs that lack most of the non-motor sequence slow each other
      down when collectively transporting a microtubule, depending on the number of
      interacting motors. This negative interference observed for a motor ensemble can
      be explained quantitatively by a mathematical model using the known physical
      properties of individual molecules of kinesin-1. The non-motor extension of
      kinesin-1 reduces this mutual interference, indicating that loose mechanical
      coupling between motors is required for efficient transport by ensembles of
      processive motors.

PMID- 18802451
TI  - Hapten-derivatized nanoparticle targeting and imaging of gene expression by
      multimodality imaging systems.
AB  - Non-invasive gene monitoring is important for most gene therapy applications to
      ensure selective gene transfer to specific cells or tissues. We developed a non
      invasive imaging system to assess the location and persistence of gene expression
      by anchoring an anti-dansyl (DNS) single-chain antibody (DNS receptor) on the
      cell surface to trap DNS-derivatized imaging probes. DNS hapten was covalently
      attached to cross-linked iron oxide (CLIO) to form a 39+/-0.5 nm DNS-CLIO
      nanoparticle imaging probe. DNS-CLIO specifically bound to DNS receptors but not
      to a control single-chain antibody receptor. DNS-CLIO (100 microM Fe) was non
      toxic to both B16/DNS (DNS receptor positive) and B16/phOx (control receptor
      positive) cells. Magnetic resonance (MR) imaging could detect as few as 10%
      B16/DNS cells in a mixture in vitro. Importantly, DNS-CLIO specifically bound to
      a B16/DNS tumor, which markedly reduced signal intensity. Similar results were
      also shown with DNS quantum dots, which specifically targeted CT26/DNS cells but
      not control CT26/phOx cells both in vitro and in vivo. These results demonstrate
      that DNS nanoparticles can systemically monitor the expression of DNS receptor in
      vivo by feasible imaging systems. This targeting strategy may provide a valuable
      tool to estimate the efficacy and specificity of different gene delivery systems
      and optimize gene therapy protocols in the clinic.

PMID- 18802452
TI  - Recent advances in p53 research: an interdisciplinary perspective.
AB  - The TP53 gene is one of the most studied genes in human cancer. In recent years,
      considerable interest was focused on mutant p53, the abnormal protein product of
      TP53 somatic or germline alleles with missense mutations that often accumulate in
      cancer cells. There is now compelling experimental evidence that many mutations
      can exert mutant-specific, gain-of-function effects by perturbing the regulation
      of expression of multiple genes. This notion is supported by the observation that
      targeted mutant p53 expression enhances the formation of specific cancers in the
      mouse even in the absence of wild-type p53 expression. In addition, clinical
      studies are producing a wealth of functional pathway data demonstrating
      correlations between specific TP53 mutations and gene expression patterns
      identified by transcriptome studies. These correlations imply that alteration of
      p53 function is critical in shaping gene expression patterns in cancer. Finally,
      progress is being made in the development of new therapeutic approaches targeting
      p53 alterations. Key advances regarding the structural, biochemical and
      functional properties of normal and mutant p53 proteins, their abnormal
      regulation and distribution in human cancers, and their associations with
      clinical and pathological cancer characteristics are reviewed. New opportunities
      for translational research for improving cancer detection, prognosis, prevention
      and therapy based upon the integration of this knowledge are described.

PMID- 18802453
TI  - Modeling recursive RNA interference.
AB  - An important application of the RNA interference (RNAi) pathway is its use as a
      small RNA-based regulatory system commonly exploited to suppress expression of
      target genes to test their function in vivo. In several published experiments,
      RNAi has been used to inactivate components of the RNAi pathway itself, a
      procedure termed recursive RNAi in this report. The theoretical basis of
      recursive RNAi is unclear since the procedure could potentially be self
      defeating, and in practice the effectiveness of recursive RNAi in published
      experiments is highly variable. A mathematical model for recursive RNAi was
      developed and used to investigate the range of conditions under which the
      procedure should be effective. The model predicts that the effectiveness of
      recursive RNAi is strongly dependent on the efficacy of RNAi at knocking down
      target gene expression. This efficacy is known to vary highly between different
      cell types, and comparison of the model predictions to published experimental
      data suggests that variation in RNAi efficacy may be the main cause of
      discrepancies between published recursive RNAi experiments in different
      organisms. The model suggests potential ways to optimize the effectiveness of
      recursive RNAi both for screening of RNAi components as well as for improved
      temporal control of gene expression in switch off-switch on experiments.

PMID- 18802454
TI  - Novel mutations in TARDBP (TDP-43) in patients with familial amyotrophic lateral
      sclerosis.
AB  - The TAR DNA-binding protein 43 (TDP-43) has been identified as the major disease
      protein in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar
      degeneration with ubiquitin inclusions (FTLD-U), defining a novel class of
      neurodegenerative conditions: the TDP-43 proteinopathies. The first pathogenic
      mutations in the gene encoding TDP-43 (TARDBP) were recently reported in familial
      and sporadic ALS patients, supporting a direct role for TDP-43 in
      neurodegeneration. In this study, we report the identification and functional
      analyses of two novel and one known mutation in TARDBP that we identified as a
      result of extensive mutation analyses in a cohort of 296 patients with variable
      neurodegenerative diseases associated with TDP-43 histopathology. Three different
      heterozygous missense mutations in exon 6 of TARDBP (p.M337V, p.N345K, and
      p.I383V) were identified in the analysis of 92 familial ALS patients (3.3%),
      while no mutations were detected in 24 patients with sporadic ALS or 180 patients
      with other TDP-43-positive neurodegenerative diseases. The presence of p.M337V,
      p.N345K, and p.I383V was excluded in 825 controls and 652 additional sporadic ALS
      patients. All three mutations affect highly conserved amino acid residues in the
      C-terminal part of TDP-43 known to be involved in protein-protein interactions.
      Biochemical analysis of TDP-43 in ALS patient cell lines revealed a substantial
      increase in caspase cleaved fragments, including the approximately 25 kDa
      fragment, compared to control cell lines. Our findings support TARDBP mutations
      as a cause of ALS. Based on the specific C-terminal location of the mutations and
      the accumulation of a smaller C-terminal fragment, we speculate that TARDBP
      mutations may cause a toxic gain of function through novel protein interactions
      or intracellular accumulation of TDP-43 fragments leading to apoptosis.

PMID- 18802455
TI  - Contact-inhibited chemotaxis in de novo and sprouting blood-vessel growth.
AB  - Blood vessels form either when dispersed endothelial cells (the cells lining the
      inner walls of fully formed blood vessels) organize into a vessel network
      (vasculogenesis), or by sprouting or splitting of existing blood vessels
      (angiogenesis). Although they are closely related biologically, no current model
      explains both phenomena with a single biophysical mechanism. Most computational
      models describe sprouting at the level of the blood vessel, ignoring how cell
      behavior drives branch splitting during sprouting. We present a cell-based,
      Glazier-Graner-Hogeweg model (also called Cellular Potts Model) simulation of the
      initial patterning before the vascular cords form lumens, based on plausible
      behaviors of endothelial cells. The endothelial cells secrete a chemoattractant,
      which attracts other endothelial cells. As in the classic Keller-Segel model,
      chemotaxis by itself causes cells to aggregate into isolated clusters. However,
      including experimentally observed VE-cadherin-mediated contact inhibition of
      chemotaxis in the simulation causes randomly distributed cells to organize into
      networks and cell aggregates to sprout, reproducing aspects of both de novo and
      sprouting blood-vessel growth. We discuss two branching instabilities responsible
      for our results. Cells at the surfaces of cell clusters attempting to migrate to
      the centers of the clusters produce a buckling instability. In a model variant
      that eliminates the surface-normal force, a dissipative mechanism drives
      sprouting, with the secreted chemical acting both as a chemoattractant and as an
      inhibitor of pseudopod extension. Both mechanisms would also apply if force
      transmission through the extracellular matrix rather than chemical signaling
      mediated cell-cell interactions. The branching instabilities responsible for our
      results, which result from contact inhibition of chemotaxis, are both generic
      developmental mechanisms and interesting examples of unusual patterning
      instabilities.

PMID- 18802456
TI  - VCAM-1 and VLA-4 modulate dendritic cell IL-12p40 production in experimental
      visceral leishmaniasis.
AB  - Vascular cell adhesion molecule-1 (VCAM-1) interacts with its major ligand very
      late antigen-4 (VLA-4) to mediate cell adhesion and transendothelial migration of
      leukocytes. We report an important role for VCAM-1/VLA-4 interactions in the
      generation of immune responses during experimental visceral leishmaniasis caused
      by Leishmania donovani. Our studies demonstrate that these molecules play no
      direct role in the recruitment of leukocytes to the infected liver, but instead
      contribute to IL-12p40-production by splenic CD8(+) dendritic cells (DC).
      Blockade of VCAM-1/VLA-4 interactions using whole antibody or anti-VCAM-1 Fab'
      fragments reduced IL-12p40 mRNA accumulation by splenic DC 5 hours after L.
      donovani infection. This was associated with reduced anti-parasitic CD4(+) T cell
      activation in the spleen and lowered hepatic IFNgamma, TNF and nitric oxide
      production by 14 days post infection. Importantly, these effects were associated
      with enhanced parasite growth in the liver in studies with either anti-VCAM-1 or
      anti-VLA-4 antibodies. These data indicate a role for VCAM-1 and VLA-4 in DC
      activation during infectious disease.

PMID- 18802457
TI  - Importance of mitochondria in survival of Cryptococcus neoformans under low
      oxygen conditions and tolerance to cobalt chloride.
AB  - Cryptococcus neoformans is an environmental fungal pathogen that requires
      atmospheric levels of oxygen for optimal growth. For the fungus to be able to
      establish an infection, it must adapt to the low oxygen concentrations in the
      host environment compared to its natural habitat. In order to investigate the
      oxygen sensing mechanism in C. neoformans, we screened T-DNA insertional mutants
      for hypoxia-mimetic cobalt chloride (CoCl(2))-sensitive mutants. All the CoCl(2)
      sensitive mutants had a growth defect under low oxygen conditions at 37 degrees
      C. The majority of mutants are compromised in their mitochondrial function, which
      is reflected by their reduced rate of respiration. Some of the mutants are also
      defective in mitochondrial membrane permeability, suggesting the importance of an
      intact respiratory system for survival under both high concentrations of CoCl(2)
      as well as low oxygen conditions. In addition, the mutants tend to accumulate
      intracellular reactive oxygen species (ROS), and all mutants show sensitivity to
      various ROS generating chemicals. Gene expression analysis revealed the
      involvement of several pathways in response to cobalt chloride. Our findings
      indicate cobalt chloride sensitivity and/or sensitivity to low oxygen conditions
      are linked to mitochondrial function, sterol and iron homeostasis,
      ubiquitination, and the ability of cells to respond to ROS. These findings imply
      that multiple pathways are involved in oxygen sensing in C. neoformans.

PMID- 18802458
TI  - Interleukin-17A mediates acquired immunity to pneumococcal colonization.
AB  - Although anticapsular antibodies confer serotype-specific immunity to
      pneumococci, children increase their ability to clear colonization before these
      antibodies appear, suggesting involvement of other mechanisms. We previously
      reported that intranasal immunization of mice with pneumococci confers CD4+ T
      cell-dependent, antibody- and serotype-independent protection against
      colonization. Here we show that this immunity, rather than preventing initiation
      of carriage, accelerates clearance over several days, accompanied by neutrophilic
      infiltration of the nasopharyngeal mucosa. Adoptive transfer of immune CD4+ T
      cells was sufficient to confer immunity to naive RAG1(-/-) mice. A critical role
      of interleukin (IL)-17A was demonstrated: mice lacking interferon-gamma or IL-4
      were protected, but not mice lacking IL-17A receptor or mice with neutrophil
      depletion. In vitro expression of IL-17A in response to pneumococci was assayed:
      lymphoid tissue from vaccinated mice expressed significantly more IL-17A than
      controls, and IL-17A expression from peripheral blood samples from immunized mice
      predicted protection in vivo. IL-17A was elicited by pneumococcal stimulation of
      tonsillar cells of children or adult blood but not cord blood. IL-17A increased
      pneumococcal killing by human neutrophils both in the absence and in the presence
      of antibodies and complement. We conclude that IL-17A mediates pneumococcal
      immunity in mice and probably in humans; its elicitation in vitro could help in
      the development of candidate pneumococcal vaccines.

PMID- 18802459
TI  - Origin, spread and demography of the Mycobacterium tuberculosis complex.
AB  - The evolutionary timing and spread of the Mycobacterium tuberculosis complex
      (MTBC), one of the most successful groups of bacterial pathogens, remains largely
      unknown. Here, using mycobacterial tandem repeat sequences as genetic markers, we
      show that the MTBC consists of two independent clades, one composed exclusively
      of M. tuberculosis lineages from humans and the other composed of both animal and
      human isolates. The latter also likely derived from a human pathogenic lineage,
      supporting the hypothesis of an original human host. Using Bayesian statistics
      and experimental data on the variability of the mycobacterial markers in infected
      patients, we estimated the age of the MTBC at 40,000 years, coinciding with the
      expansion of "modern" human populations out of Africa. Furthermore, coalescence
      analysis revealed a strong and recent demographic expansion in almost all M.
      tuberculosis lineages, which coincides with the human population explosion over
      the last two centuries. These findings thus unveil the dynamic dimension of the
      association between human host and pathogen populations.

PMID- 18802460
TI  - Kaposi's sarcoma-associated herpesvirus K7 induces viral G protein-coupled
      receptor degradation and reduces its tumorigenicity.
AB  - The Kaposi's sarcoma-associated herpesvirus (KSHV) genome encodes a G protein
      coupled receptor (vGPCR). vGPCR is a ligand-independent, constitutively active
      signaling molecule that promotes cell growth and proliferation; however, it is
      not clear how vGPCR is negatively regulated. We report here that the KSHV K7
      small membrane protein interacts with vGPCR and induces its degradation, thereby
      dampening vGPCR signaling. K7 interaction with vGPCR is readily detected in
      transiently transfected human cells. Mutational analyses reveal that the K7
      transmembrane domain is necessary and sufficient for this interaction.
      Biochemical and confocal microscopy studies indicate that K7 retains vGPCR in the
      endoplasmic reticulum (ER) and induces vGPCR proteasomeal degradation. Indeed,
      the knockdown of K7 by shRNA-mediated silencing increases vGPCR protein
      expression in BCBL-1 cells that are induced for KSHV lytic replication.
      Interestingly, K7 expression significantly reduces vGPCR tumorigenicity in nude
      mice. These findings define a viral factor that negatively regulates vGPCR
      protein expression and reveal a post-translational event that modulates GPCR
      dependent transformation and tumorigenicity.

PMID- 18802461
TI  - Corona is required for higher-order assembly of transverse filaments into full
      length synaptonemal complex in Drosophila oocytes.
AB  - The synaptonemal complex (SC) is an intricate structure that forms between
      homologous chromosomes early during the meiotic prophase, where it mediates
      homolog pairing interactions and promotes the formation of genetic exchanges. In
      Drosophila melanogaster, C(3)G protein forms the transverse filaments (TFs) of
      the SC. The N termini of C(3)G homodimers localize to the Central Element (CE) of
      the SC, while the C-termini of C(3)G connect the TFs to the chromosomes via
      associations with the axial elements/lateral elements (AEs/LEs) of the SC. Here,
      we show that the Drosophila protein Corona (CONA) co-localizes with C(3)G in a
      mutually dependent fashion and is required for the polymerization of C(3)G into
      mature thread-like structures, in the context both of paired homologous
      chromosomes and of C(3)G polycomplexes that lack AEs/LEs. Although AEs assemble
      in cona oocytes, they exhibit defects that are characteristic of c(3)G mutant
      oocytes, including failure of AE alignment and synapsis. These results
      demonstrate that CONA, which does not contain a coiled coil domain, is required
      for the stable 'zippering' of TFs to form the central region of the Drosophila
      SC. We speculate that CONA's role in SC formation may be similar to that of the
      mammalian CE proteins SYCE2 and TEX12. However, the observation that AE alignment
      and pairing occurs in Tex12 and Syce2 mutant meiocytes but not in cona oocytes
      suggests that the SC plays a more critical role in the stable association of
      homologs in Drosophila than it does in mammalian cells.

PMID- 18802462
TI  - Screening and replication using the same data set: testing strategies for family
      based studies in which all probands are affected.
AB  - For genome-wide association studies in family-based designs, we propose a
      powerful two-stage testing strategy that can be applied in situations in which
      parent-offspring trio data are available and all offspring are affected with the
      trait or disease under study. In the first step of the testing strategy, we
      construct estimators of genetic effect size in the completely ascertained sample
      of affected offspring and their parents that are statistically independent of the
      family-based association/transmission disequilibrium tests (FBATs/TDTs) that are
      calculated in the second step of the testing strategy. For each marker, the
      genetic effect is estimated (without requiring an estimate of the SNP allele
      frequency) and the conditional power of the corresponding FBAT/TDT is computed.
      Based on the power estimates, a weighted Bonferroni procedure assigns an
      individually adjusted significance level to each SNP. In the second stage, the
      SNPs are tested with the FBAT/TDT statistic at the individually adjusted
      significance levels. Using simulation studies for scenarios with up to 1,000,000
      SNPs, varying allele frequencies and genetic effect sizes, the power of the
      strategy is compared with standard methodology (e.g., FBATs/TDTs with Bonferroni
      correction). In all considered situations, the proposed testing strategy
      demonstrates substantial power increases over the standard approach, even when
      the true genetic model is unknown and must be selected based on the conditional
      power estimates. The practical relevance of our methodology is illustrated by an
      application to a genome-wide association study for childhood asthma, in which we
      detect two markers meeting genome-wide significance that would not have been
      detected using standard methodology.

PMID- 18802463
TI  - An approximate bayesian estimator suggests strong, recurrent selective sweeps in
      Drosophila.
AB  - The recurrent fixation of newly arising, beneficial mutations in a species
      reduces levels of linked neutral variability. Models positing frequent weakly
      beneficial substitutions or, alternatively, rare, strongly selected substitutions
      predict similar average effects on linked neutral variability, if the product of
      the rate and strength of selection is held constant. We propose an approximate
      Bayesian (ABC) polymorphism-based estimator that can be used to distinguish
      between these models, and apply it to multi-locus data from Drosophila
      melanogaster. We investigate the extent to which inference about the strength of
      selection is sensitive to assumptions about the underlying distributions of the
      rates of substitution and recombination, the strength of selection, heterogeneity
      in mutation rate, as well as the population's demographic history. We show that
      assuming fixed values of selection parameters in estimation leads to
      overestimates of the strength of selection and underestimates of the rate. We
      estimate parameters for an African population of D. melanogaster (s approximately
      2E-03, ) and compare these to previous estimates. Finally, we show that surveying
      larger genomic regions is expected to lend much more discriminatory power to the
      approach. It will thus be of great interest to apply this method to emerging
      whole-genome polymorphism data sets in many taxa.

PMID- 18802464
TI  - Protective effect of Toll-like receptor 4 in pulmonary vaccinia infection.
AB  - Innate immune responses are essential for controlling poxvirus infection. The
      threat of a bioterrorist attack using Variola major, the smallpox virus, or
      zoonotic transmission of other poxviruses has renewed interest in understanding
      interactions between these viruses and their hosts. We recently determined that
      TLR3 regulates a detrimental innate immune response that enhances replication,
      morbidity, and mortality in mice in response to vaccinia virus, a model pathogen
      for studies of poxviruses. To further investigate Toll-like receptor signaling in
      vaccinia infection, we first focused on TRIF, the only known adapter protein for
      TLR3. Unexpectedly, bioluminescence imaging showed that mice lacking TRIF are
      more susceptible to vaccinia infection than wild-type mice. We then focused on
      TLR4, the other Toll-like receptor that signals through TRIF. Following
      respiratory infection with vaccinia, mice lacking TLR4 signaling had greater
      viral replication, hypothermia, and mortality than control animals. The mechanism
      of TLR4-mediated protection was not due to increased release of proinflammatory
      cytokines or changes in total numbers of immune cells recruited to the lung.
      Challenge of primary bone marrow macrophages isolated from TLR4 mutant and
      control mice suggested that TLR4 recognizes a viral ligand rather than an
      endogenous ligand. These data establish that TLR4 mediates a protective innate
      immune response against vaccinia virus, which informs development of new vaccines
      and therapeutic agents targeted against poxviruses.

PMID- 18802465
TI  - A mouse model of harlequin ichthyosis delineates a key role for Abca12 in lipid
      homeostasis.
AB  - Harlequin Ichthyosis (HI) is a severe and often lethal hyperkeratotic skin
      disease caused by mutations in the ABCA12 transport protein. In keratinocytes,
      ABCA12 is thought to regulate the transfer of lipids into small intracellular
      trafficking vesicles known as lamellar bodies. However, the nature and scope of
      this regulation remains unclear. As part of an original recessive mouse ENU
      mutagenesis screen, we have identified and characterised an animal model of HI
      and showed that it displays many of the hallmarks of the disease including
      hyperkeratosis, loss of barrier function, and defects in lipid homeostasis. We
      have used this model to follow disease progression in utero and present evidence
      that loss of Abca12 function leads to premature differentiation of basal
      keratinocytes. A comprehensive analysis of lipid levels in mutant epidermis
      demonstrated profound defects in lipid homeostasis, illustrating for the first
      time the extent to which Abca12 plays a pivotal role in maintaining lipid balance
      in the skin. To further investigate the scope of Abca12's activity, we have
      utilised cells from the mutant mouse to ascribe direct transport functions to the
      protein and, in doing so, we demonstrate activities independent of its role in
      lamellar body function. These cells have severely impaired lipid efflux leading
      to intracellular accumulation of neutral lipids. Furthermore, we identify Abca12
      as a mediator of Abca1-regulated cellular cholesterol efflux, a finding that may
      have significant implications for other diseases of lipid metabolism and
      homeostasis, including atherosclerosis.

PMID- 18802466
TI  - Impact of capsular switch on invasive pneumococcal disease incidence in a
      vaccinated population.
AB  - BACKGROUND: Despite the dramatic decline in the incidence of invasive
      pneumococcal disease (IPD) observed since the introduction of conjugate
      vaccination, it is feared that several factors may undermine the future
      effectiveness of the vaccines. In particular, pathogenic pneumococci may switch
      their capsular types and evade vaccine-conferred immunity. METHODOLOGY/PRINCIPAL
      FINDINGS: Here, we first review the literature and summarize the available
      epidemiological data on capsular switch for S. pneumoniae. We estimate the weekly
      probability that a persistently carried strain may switch its capsule from four
      studies, totalling 516 children and 6 years of follow-up, at 1.5x10(-3)/week
      [4.6x10(-5)-4.8x10(-3)/week]. There is not enough power to assess an increase in
      this frequency in vaccinated individuals. Then, we use a mathematical model of
      pneumococcal transmission to quantify the impact of capsular switch on the
      incidence of IPD in a vaccinated population. In this model, we investigate a wide
      range of values for the frequency of vaccine-selected capsular switch.
      Predictions show that, with vaccine-independent switching only, IPD incidence in
      children should be down by 48% 5 years after the introduction of the vaccine with
      high coverage. Introducing vaccine-selected capsular switch at a frequency up to
      0.01/week shows little effect on this decrease; yearly, at most 3 excess cases of
      IPD per 10(6) children might occur due to switched pneumococcal strains.
      CONCLUSIONS: Based on all available data and model predictions, the existence of
      capsular switch by itself should not impact significantly the efficacy of
      pneumococcal conjugate vaccination on IPD incidence. This optimistic result
      should be tempered by the fact that the selective pressure induced by the vaccine
      is currently increasing along with vaccine coverage worldwide; continued
      surveillance of pneumococcal populations remains of the utmost importance, in
      particular during clinical trials of the new conjugate vaccines.

PMID- 18802467
TI  - A publish-subscribe model of genetic networks.
AB  - We present a simple model of genetic regulatory networks in which regulatory
      connections among genes are mediated by a limited number of signaling molecules.
      Each gene in our model produces (publishes) a single gene product, which
      regulates the expression of other genes by binding to regulatory regions that
      correspond (subscribe) to that product. We explore the consequences of this
      publish-subscribe model of regulation for the properties of single networks and
      for the evolution of populations of networks. Degree distributions of randomly
      constructed networks, particularly multimodal in-degree distributions, which
      depend on the length of the regulatory sequences and the number of possible gene
      products, differed from simpler Boolean NK models. In simulated evolution of
      populations of networks, single mutations in regulatory or coding regions
      resulted in multiple changes in regulatory connections among genes, or
      alternatively in neutral change that had no effect on phenotype. This resulted in
      remarkable evolvability in both number and length of attractors, leading to
      evolved networks far beyond the expectation of these measures based on random
      distributions. Surprisingly, this rapid evolution was not accompanied by changes
      in degree distribution; degree distribution in the evolved networks was not
      substantially different from that of randomly generated networks. The publish
      subscribe model also allows exogenous gene products to create an environment,
      which may be noisy or stable, in which dynamic behavior occurs. In simulations,
      networks were able to evolve moderate levels of both mutational and environmental
      robustness.

PMID- 18802468
TI  - Courtship initiation is stimulated by acoustic signals in Drosophila
      melanogaster.
AB  - Finding a mating partner is a critical task for many organisms. It is in the
      interest of males to employ multiple sensory modalities to search for females. In
      Drosophila melanogaster, vision is thought to be the most important courtship
      stimulating cue at long distance, while chemosensory cues are used at relatively
      short distance. In this report, we show that when visual cues are not available,
      sounds produced by the female allow the male to detect her presence in a large
      arena. When the target female was artificially immobilized, the male spent a
      prolonged time searching before starting courtship. This delay in courtship
      initiation was completely rescued by playing either white noise or recorded fly
      movement sounds to the male, indicating that the acoustic and/or seismic stimulus
      produced by movement stimulates courtship initiation, most likely by increasing
      the general arousal state of the male. Mutant males expressing tetanus toxin
      (TNT) under the control of Gr68a-GAL4 had a defect in finding active females and
      a delay in courtship initiation in a large arena, but not in a small arena. Gr68a
      GAL4 was found to be expressed pleiotropically not only in putative gustatory
      pheromone receptor neurons but also in mechanosensory neurons, suggesting that
      Gr68a-positive mechanosensory neurons, not gustatory neurons, provide motion
      detection necessary for courtship initiation. TNT/Gr68a males were capable of
      discriminating the copulation status and age of target females in courtship
      conditioning, indicating that female discrimination and formation of olfactory
      courtship memory are independent of the Gr68a-expressing neurons that subserve
      gustation and mechanosensation. This study suggests for the first time that
      mechanical signals generated by a female fly have a prominent effect on males'
      courtship in the dark and leads the way to studying how multimodal sensory
      information and arousal are integrated in behavioral decision making.

PMID- 18802469
TI  - Deletion of the pluripotency-associated Tex19.1 gene causes activation of
      endogenous retroviruses and defective spermatogenesis in mice.
AB  - As genetic information is transmitted through successive generations, it passes
      between pluripotent cells in the early embryo and germ cells in the developing
      foetus and adult animal. Tex19.1 encodes a protein of unknown function, whose
      expression is restricted to germ cells and pluripotent cells. During male
      spermatogenesis, Tex19.1 expression is highest in mitotic spermatogonia and
      diminishes as these cells differentiate and progress through meiosis. In
      pluripotent stem cells, Tex19.1 expression is also downregulated upon
      differentiation. However, it is not clear whether Tex19.1 has an essential
      function in germ cells or pluripotent stem cells, or what that function might be.
      To analyse the potential role of Tex19.1 in pluripotency or germ cell function we
      have generated Tex19.1(-/-) knockout mice and analysed the Tex19.1(-/-) mutant
      phenotype. Adult Tex19.1(-/-) knockout males exhibit impaired spermatogenesis.
      Immunostaining and histological analysis revealed defects in meiotic chromosome
      synapsis, the persistence of DNA double-strand breaks during meiosis, and a loss
      of post-meiotic germ cells in the testis. Furthermore, expression of a class of
      endogenous retroviruses is upregulated during meiosis in the Tex19.1(-/-) testes.
      Increased transposition of endogenous retroviruses in the germline of Tex19.1(-/
      ) mutant mice, and the concomitant increase in DNA damage, may be sufficient to
      disrupt the normal processes of recombination and chromosome synapsis during
      meiosis and cause defects in spermatogenesis. Our results suggest that Tex19.1 is
      part of a specialised mechanism that operates in the germline to repress
      transposable genetic elements and maintain genomic stability through successive
      generations.

PMID- 18802470
TI  - Computational structural analysis: multiple proteins bound to DNA.
AB  - BACKGROUND: With increasing numbers of crystal structures of proteinratioDNA and
      proteinratioproteinratioDNA complexes publically available, it is now possible to
      extract sufficient structural, physical-chemical and thermodynamic parameters to
      make general observations and predictions about their interactions. In
      particular, the properties of macromolecular assemblies of multiple proteins
      bound to DNA have not previously been investigated in detail.
      METHODOLOGY/PRINCIPAL FINDINGS: We have performed computational structural
      analyses on macromolecular assemblies of multiple proteins bound to DNA using a
      variety of different computational tools: PISA; PROMOTIF; X3DNA; ReadOut; DDNA
      and DCOMPLEX. Additionally, we have developed and employed an algorithm for
      approximate collision detection and overlapping volume estimation of two
      macromolecules. An implementation of this algorithm is available at
      http://promoterplot.fmi.ch/Collision1/. The results obtained are compared with
      structural, physical-chemical and thermodynamic parameters from
      proteinratioprotein and single proteinratioDNA complexes. Many of interface
      properties of multiple proteinratioDNA complexes were found to be very similar to
      those observed in binary proteinratioDNA and proteinratioprotein complexes.
      However, the conformational change of the DNA upon protein binding is
      significantly higher when multiple proteins bind to it than is observed when
      single proteins bind. The water mediated contacts are less important (found in
      less quantity) between the interfaces of components in ternary
      (proteinratioproteinratioDNA) complexes than in those of binary complexes
      (proteinratioprotein and proteinratioDNA).The thermodynamic stability of ternary
      complexes is also higher than in the binary interactions. Greater specificity and
      affinity of multiple proteins binding to DNA in comparison with binary protein
      DNA interactions were observed. However, protein-protein binding affinities are
      stronger in complexes without the presence of DNA. CONCLUSIONS/SIGNIFICANCE: Our
      results indicate that the interface properties: interface area; number of
      interface residues/atoms and hydrogen bonds; and the distribution of interface
      residues, hydrogen bonds, van der Walls contacts and secondary structure motifs
      are independent of whether or not a protein is in a binary or ternary complex
      with DNA. However, changes in the shape of the DNA reduce the off-rate of the
      proteins which greatly enhances the stability and specificity of ternary
      complexes compared to binary ones.

PMID- 18802471
TI  - MHC class I endosomal and lysosomal trafficking coincides with exogenous antigen
      loading in dendritic cells.
AB  - BACKGROUND: Cross-presentation by dendritic cells (DCs) is a crucial prerequisite
      for effective priming of cytotoxic T-cell responses against bacterial, viral and
      tumor antigens; however, this antigen presentation pathway remains poorly
      defined. METHODOLOGY/PRINCIPAL FINDINGS: In order to develop a comprehensive
      understanding of this process, we tested the hypothesis that the internalization
      of MHC class I molecules (MHC-I) from the cell surface is directly involved in
      cross-presentation pathway and the loading of antigenic peptides. Here we provide
      the first examination of the internalization of MHC-I in DCs and we demonstrate
      that the cytoplasmic domain of MHC-I appears to act as an addressin domain to
      route MHC-I to both endosomal and lysosomal compartments of DCs, where it is
      demonstrated that loading of peptides derived from exogenously-derived proteins
      occurs. Furthermore, by chasing MHC-I from the cell surface of normal and
      transgenic DCs expressing mutant forms of MHC-I, we observe that a tyrosine-based
      endocytic trafficking motif is required for the constitutive internalization of
      MHC-I molecules from the cell surface into early endosomes and subsequently deep
      into lysosomal peptide-loading compartments. Finally, our data support the
      concept that multiple pathways of peptide loading of cross-presented antigens may
      exist depending on the chemical nature and size of the antigen requiring
      processing. CONCLUSIONS/SIGNIFICANCE: We conclude that DCs have 'hijacked' and
      adapted a common vacuolar/endocytic intracellular trafficking pathway to
      facilitate MHC I access to the endosomal and lysosomal compartments where antigen
      processing and loading and antigen cross-presentation takes place.

PMID- 18802472
TI  - gammaCOP is required for apical protein secretion and epithelial morphogenesis in
      Drosophila melanogaster.
AB  - BACKGROUND: There is increasing evidence that tissue-specific modifications of
      basic cellular functions play an important role in development and disease. To
      identify the functions of COPI coatomer-mediated membrane trafficking in
      Drosophila development, we were aiming to create loss-of-function mutations in
      the gammaCOP gene, which encodes a subunit of the COPI coatomer complex.
      PRINCIPAL FINDINGS: We found that gammaCOP is essential for the viability of the
      Drosophila embryo. In the absence of zygotic gammaCOP activity, embryos die late
      in embryogenesis and display pronounced defects in morphogenesis of the embryonic
      epidermis and of tracheal tubes. The coordinated cell rearrangements and cell
      shape changes during tracheal tube morphogenesis critically depend on apical
      secretion of certain proteins. Investigation of tracheal morphogenesis in
      gammaCOP loss-of-function mutants revealed that several key proteins required for
      tracheal morphogenesis are not properly secreted into the apical lumen. As a
      consequence, gammaCOP mutants show defects in cell rearrangements during branch
      elongation, in tube dilation, as well as in tube fusion. We present genetic
      evidence that a specific subset of the tracheal defects in gammaCOP mutants is
      due to the reduced secretion of the Zona Pellucida protein Piopio. Thus, we
      identified a critical target protein of COPI-dependent secretion in epithelial
      tube morphogenesis. CONCLUSIONS/SIGNIFICANCE: These studies highlight the role of
      COPI coatomer-mediated vesicle trafficking in both general and tissue-specific
      secretion in a multicellular organism. Although COPI coatomer is generally
      required for protein secretion, we show that the phenotypic effect of gammaCOP
      mutations is surprisingly specific. Importantly, we attribute a distinct aspect
      of the gammaCOP phenotype to the effect on a specific key target protein.

PMID- 18802473
TI  - Missense mutation in exon 2 of SLC36A1 responsible for champagne dilution in
      horses.
AB  - Champagne coat color in horses is controlled by a single, autosomal-dominant gene
      (CH). The phenotype produced by this gene is valued by many horse breeders, but
      can be difficult to distinguish from the effect produced by the Cream coat color
      dilution gene (CR). Three sires and their families segregating for CH were tested
      by genome scanning with microsatellite markers. The CH gene was mapped within a 6
      cM region on horse chromosome 14 (LOD = 11.74 for theta = 0.00). Four candidate
      genes were identified within the region, namely SPARC [Secreted protein, acidic,
      cysteine-rich (osteonectin)], SLC36A1 (Solute Carrier 36 family A1), SLC36A2
      (Solute Carrier 36 family A2), and SLC36A3 (Solute Carrier 36 family A3). SLC36A3
      was not expressed in skin tissue and therefore not considered further. The other
      three genes were sequenced in homozygotes for CH and homozygotes for the absence
      of the dilution allele (ch). SLC36A1 had a nucleotide substitution in exon 2 for
      horses with the champagne phenotype, which resulted in a transition from a
      threonine amino acid to an arginine amino acid (T63R). The association of the
      single nucleotide polymorphism (SNP) with the champagne dilution phenotype was
      complete, as determined by the presence of the nucleotide variant among all 85
      horses with the champagne dilution phenotype and its absence among all 97 horses
      without the champagne phenotype. This is the first description of a phenotype
      associated with the SLC36A1 gene.

PMID- 18802474
TI  - A combined computational-experimental analyses of selected metabolic enzymes in
      Pseudomonas species.
AB  - Comparative genomic analysis has revolutionized our ability to predict the
      metabolic subsystems that occur in newly sequenced genomes, and to explore the
      functional roles of the set of genes within each subsystem. These computational
      predictions can considerably reduce the volume of experimental studies required
      to assess basic metabolic properties of multiple bacterial species. However,
      experimental validations are still required to resolve the apparent
      inconsistencies in the predictions by multiple resources. Here, we present
      combined computational-experimental analyses on eight completely sequenced
      Pseudomonas species. Comparative pathway analyses reveal that several pathways
      within the Pseudomonas species show high plasticity and versatility. Potential
      bypasses in 11 metabolic pathways were identified. We further confirmed the
      presence of the enzyme O-acetyl homoserine (thiol) lyase (EC: 2.5.1.49) in P.
      syringae pv. tomato that revealed inconsistent annotations in KEGG and in the
      recently published SYSTOMONAS database. These analyses connect and integrate
      systematic data generation, computational data interpretation, and experimental
      validation and represent a synergistic and powerful means for conducting
      biological research.

PMID- 18802475
TI  - Effect of exercise training on calpain systems in lean and obese Zucker rats.
AB  - Exercise training plays a major role in the improving physiology of diabetes.
      Herein we aimed to investigate the influence of exercise upon the calcium
      dependent calpain-isoform expressions of lean or obese Zucker rats, a model of
      obesity and type II diabetes (NIDDM). Five-month-old rats were divided: (1) obese
      sedentary (OS, n=7); (2) obese exercise (OE, n=7); (3) lean sedentary (LS, n=7);
      (4) lean exercise (LE, n=7). After 2-month exercise (treadmill running), the body
      weight (BW) and expression of calpain 10, mu-calpain, and m-calpain in skeletal
      muscles were determined by RT-PCR, using beta-actin as internal standard. We
      found exercise is useful for BW lossing, especially in the obese rats. The BW
      difference between OS and OE rats (69 g vs. 18.2 g) was more significantly than
      that between LS and LE rats (41.8 g vs. 28.7 g). The calpain 10 expression of LS
      rats (0.965) was lower than that of LE rats (1.006), whereas those of OS and OE
      were comparable. The mu- or m-calpain expressions of sedentary groups (OS, LS)
      was significantly higher than those of exercise groups (OE, LE). The mu-calpain
      expression (1.13/0.92) and m-calpain expression (1.01/0.99) of OS/LS rats was
      significantly higher than those of OE/LE rats [1.07/0.9 (micro-calpain);
      0.97/0.95 (m-calpain)]. We concluded that the micro- or m-calpains in skeletal
      muscle are regulated by exercise in both lean and obese Zucker rats. Exercise and
      BW controlling might improve the physiopathology of obesity and diabetes. Both
      micro- or m-calpains might become useful markers for prognoses of diabetes.

PMID- 18802476
TI  - Ectopic expression of neural autoantigen in mouse liver suppresses experimental
      autoimmune neuroinflammation by inducing antigen-specific Tregs.
AB  - Tregs are important mediators of immune tolerance to self antigens, and it has
      been suggested that Treg inactivation may cause autoimmune disease. Therefore,
      immunotherapy approaches that aim to restore or expand autoantigen-specific Treg
      activity might be beneficial for the treatment of autoimmune disease. Here we
      report that Treg-mediated suppression of autoimmune disease can be achieved in
      vivo by taking advantage of the ability of the liver to promote immune tolerance.
      Expression of the neural autoantigen myelin basic protein (MBP) in the liver was
      accomplished stably in liver-specific MBP transgenic mice and transiently using
      gene transfer to liver cells in vivo. Such ectopic MBP expression induced
      protection from autoimmune neuroinflammation in a mouse model of multiple
      sclerosis. Protection from autoimmunity was mediated by MBP-specific
      CD4+CD25+Foxp3+ Tregs, as demonstrated by the ability of these cells to prevent
      disease when adoptively transferred into nontransgenic mice and to suppress
      conventional CD4+CD25- T cell proliferation after antigen-specific stimulation
      with MBP in vitro. The generation of MBP-specific CD4+CD25+Foxp3+ Tregs in vivo
      depended on expression of MBP in the liver, but not in skin, and occurred by TGF
      beta-dependent peripheral conversion from conventional non-Tregs. Our findings
      indicate that autoantigen expression in the liver may generate autoantigen
      specific Tregs. Thus, targeting of autoantigens to hepatocytes may be a novel
      approach to prevention or treatment of autoimmune diseases.

PMID- 18802477
TI  - In utero supplementation with methyl donors enhances allergic airway disease in
      mice.
AB  - Asthma is a complex heritable disease that is increasing in prevalence and
      severity, particularly in developed countries such as the United States, where
      11% of the population is affected. The contribution of environmental and genetic
      factors to this growing epidemic is currently not well understood. We developed
      the hypothesis, based on previous literature, that changes in DNA methylation
      resulting in aberrant gene transcription may enhance the risk of developing
      allergic airway disease. Our findings indicate that in mice, a maternal diet
      supplemented with methyl donors enhanced the severity of allergic airway disease
      that was inherited transgenerationally. Using a genomic approach, we discovered
      82 gene-associated loci that were differentially methylated after in utero
      supplementation with a methyl-rich diet. These methylation changes were
      associated with decreased transcriptional activity and increased disease
      severity. Runt-related transcription factor 3 (Runx3), a gene known to negatively
      regulate allergic airway disease, was found to be excessively methylated, and
      Runx3 mRNA and protein levels were suppressed in progeny exposed in utero to a
      high-methylation diet. Moreover, treatment with a demethylating agent increased
      Runx3 gene transcription, further supporting our claim that a methyl-rich diet
      can affect methylation status and consequent transcriptional regulation. Our
      findings indicate that dietary factors can modify the heritable risk of allergic
      airway disease through epigenetic mechanisms during a vulnerable period of fetal
      development in mice.

PMID- 18802478
TI  - GSK-3beta in mouse fibroblasts controls wound healing and fibrosis through an
      endothelin-1-dependent mechanism.
AB  - Glycogen synthase kinase-3 (GSK-3) is a widely expressed and highly conserved
      serine/threonine protein kinase encoded by 2 genes, GSK3A and GSK3B. GSK-3 is
      thought to be involved in tissue repair and fibrogenesis, but its role in these
      processes is currently unknown. To investigate the function of GSK-3beta in
      fibroblasts, we generated mice harboring a fibroblast-specific deletion of Gsk3b
      and evaluated their wound-healing and fibrogenic responses. We have shown that
      Gsk3b-conditional-KO mice (Gsk3b-CKO mice) exhibited accelerated wound closure,
      increased fibrogenesis, and excessive scarring compared with control mice. In
      addition, Gsk3b-CKO mice showed elevated collagen production, decreased cell
      apoptosis, elevated levels of profibrotic alpha-SMA, and increased myofibroblast
      formation during wound healing. In cultured Gsk3b-CKO fibroblasts, adhesion,
      spreading, migration, and contraction were enhanced. Both Gsk3b-CKO mice and
      fibroblasts showed elevated expression and production of endothelin-1 (ET-1)
      compared with control mice and cells. Antagonizing ET-1 reversed the phenotype of
      Gsk3b-CKO fibroblasts and mice. Thus, GSK-3beta appears to control the
      progression of wound healing and fibrosis by modulating ET-1 levels. These
      results suggest that targeting the GSK-3beta pathway or ET-1 may be of benefit in
      controlling tissue repair and fibrogenic responses in vivo.

PMID- 18802479
TI  - CTLs are targeted to kill beta cells in patients with type 1 diabetes through
      recognition of a glucose-regulated preproinsulin epitope.
AB  - The final pathway of beta cell destruction leading to insulin deficiency,
      hyperglycemia, and clinical type 1 diabetes is unknown. Here we show that
      circulating CTLs can kill beta cells via recognition of a glucose-regulated
      epitope. First, we identified 2 naturally processed epitopes from the human
      preproinsulin signal peptide by elution from HLA-A2 (specifically, the protein
      encoded by the A*0201 allele) molecules. Processing of these was unconventional,
      requiring neither the proteasome nor transporter associated with processing
      (TAP). However, both epitopes were major targets for circulating effector CD8+ T
      cells from HLA-A2+ patients with type 1 diabetes. Moreover, cloned preproinsulin
      signal peptide-specific CD8+ T cells killed human beta cells in vitro.
      Critically, at high glucose concentration, beta cell presentation of
      preproinsulin signal epitope increased, as did CTL killing. This study provides
      direct evidence that autoreactive CTLs are present in the circulation of patients
      with type 1 diabetes and that they can kill human beta cells. These results also
      identify a mechanism of self-antigen presentation that is under
      pathophysiological regulation and could expose insulin-producing beta cells to
      increasing cytotoxicity at the later stages of the development of clinical
      diabetes. Our findings suggest that autoreactive CTLs are important targets for
      immune-based interventions in type 1 diabetes and argue for early, aggressive
      insulin therapy to preserve remaining beta cells.

PMID- 18802480
TI  - Hedgehog signaling regulates epithelial-mesenchymal transition during biliary
      fibrosis in rodents and humans.
AB  - Epithelial-mesenchymal transitions (EMTs) play an important role in tissue
      construction during embryogenesis, and evidence suggests that this process may
      also help to remodel some adult tissues after injury. Activation of the hedgehog
      (Hh) signaling pathway regulates EMT during development. This pathway is also
      induced by chronic biliary injury, a condition in which EMT has been suggested to
      have a role. We evaluated the hypothesis that Hh signaling promotes EMT in adult
      bile ductular cells (cholangiocytes). In liver sections from patients with
      chronic biliary injury and in primary cholangiocytes isolated from rats that had
      undergone bile duct ligation (BDL), an experimental model of biliary fibrosis,
      EMT was localized to cholangiocytes with Hh pathway activity. Relief of ductal
      obstruction in BDL rats reduced Hh pathway activity, EMT, and biliary fibrosis.
      In mouse cholangiocytes, coculture with myofibroblastic hepatic stellate cells, a
      source of soluble Hh ligands, promoted EMT and cell migration. Addition of Hh
      neutralizing antibodies to cocultures blocked these effects. Finally, we found
      that EMT responses to BDL were enhanced in patched-deficient mice, which display
      excessive activation of the Hh pathway. Together, these data suggest that
      activation of Hh signaling promotes EMT and contributes to the evolution of
      biliary fibrosis during chronic cholestasis.

PMID- 18802481
TI  - Regulatory B cells inhibit EAE initiation in mice while other B cells promote
      disease progression.
AB  - EAE is a mouse T cell-mediated autoimmune disease of the CNS used to model the
      human condition MS. The contributions of B cells to EAE initiation and
      progression are unclear. In this study, we have shown that EAE disease initiation
      and progression are differentially influenced by the depletion of B cells from
      mice with otherwise intact immune systems. CD20 antibody-mediated B cell
      depletion before EAE induction substantially exacerbated disease symptoms and
      increased encephalitogenic T cell influx into the CNS. Increased symptom severity
      resulted from the depletion of a rare IL-10-producing CD1dhiCD5+ regulatory B
      cell subset (B10 cells), since the adoptive transfer of splenic B10 cells before
      EAE induction normalized EAE in B cell-depleted mice. While transfer of
      regulatory B10 cells was maximally effective during early EAE initiation, they
      had no obvious role during disease progression. Rather, B cell depletion during
      EAE disease progression dramatically suppressed symptoms. Specifically, B cells
      were required for the generation of CD4+ T cells specific for CNS autoantigen and
      the entry of encephalitogenic T cells into the CNS during disease progression.
      These results demonstrate reciprocal regulatory roles for B cells during EAE
      immunopathogenesis. The therapeutic effect of B cell depletion for the treatment
      of autoimmunity may therefore depend on the relative contributions and the timing
      of these opposing B cell activities during the course of disease initiation and
      pathogenesis.

PMID- 18802482
TI  - Neutrophil activation by the tissue factor/Factor VIIa/PAR2 axis mediates fetal
      death in a mouse model of antiphospholipid syndrome.
AB  - Women with antiphospholipid syndrome (APS), a condition characterized by the
      presence of antiphospholipid antibodies (aPL), often suffer pregnancy-related
      complications, including miscarriage. We have previously shown that C5a induction
      of tissue factor (TF) expression in neutrophils contributes to respiratory burst,
      trophoblast injury, and pregnancy loss in mice treated with aPL. Here we analyzed
      how TF contributes to neutrophil activation and trophoblast injury in this model.
      Neutrophils from aPL-treated mice expressed protease-activated receptor 2 (PAR2),
      and stimulation of this receptor led to neutrophil activation, trophoblast
      injury, and fetal death. An antibody specific for human TF that has little impact
      on coagulation, but potently inhibits TF/Factor VIIa (FVIIa) signaling through
      PAR2, inhibited aPL-induced neutrophil activation in mice that expressed human
      TF. Genetic deletion of the TF cytoplasmic domain, which allows interaction
      between TF and PAR2, reduced aPL-induced neutrophil activation in aPL-treated
      mice. Par2-/- mice treated with aPL exhibited reduced neutrophil activation and
      normal pregnancies, which indicates that PAR2 plays an important role in the
      pathogenesis of aPL-induced fetal injury. We also demonstrated that simvastatin
      and pravastatin decreased TF and PAR2 expression on neutrophils and prevented
      pregnancy loss. Our results suggest that TF/FVIIa/PAR2 signaling mediates
      neutrophil activation and fetal death in APS and that statins may be a good
      treatment for women with aPL-induced pregnancy complications.

PMID- 18802483
TI  - Coaxing the liver into preventing autoimmune disease in the brain.
AB  - The liver has several unique immunological properties that affect T cell
      activation and immune regulation. Recent studies have uncovered opportunities for
      the treatment of genetic disease by directing expression of the functional
      therapeutic protein to hepatocytes. In a new study in this issue of the JCI, Luth
      and colleagues demonstrate that hepatic expression of a brain protein is
      protective against neuroinflammatory disease in a mouse model of human MS (see
      the related article beginning on page 3403). Suppression of autoimmunity was
      dependent on transgene expression in the liver and was mediated by induction of
      antigen-specific CD4+CD25+Foxp3+ Tregs. These findings suggest that the
      introduction of antigens to the liver may have potential as a preventative or
      therapeutic intervention for autoimmune disease.

PMID- 18802484
TI  - Paradox of B cell-targeted therapies.
AB  - The use of antibodies against the human B cell surface protein CD20 represents
      the most advanced therapeutic approach among the B cell-depleting armamentarium
      for the treatment of autoimmune disorders. However, recent evidence indicates
      that B cells can also be essential for suppressing unwanted autoaggressive T cell
      responses, and therefore, a more careful evaluation of which types of autoimmune
      disorders this therapy should be utilized for, and at which phases of disease
      this therapy should be applied, is necessary. In this issue of the JCI,
      Matsushita et al. report that the timing of this therapy is critical for the
      management of EAE, a mouse model of human MS (see the related article beginning
      on page 3420). The results suggest the existence of two opposite actions executed
      by B cells during the course of autoimmune pathology; CD1dhiCD5+ regulatory B
      cells suppress EAE induction, whereas B cells are required for the expansion of
      autoantigen-specific T cells during disease progression. Given the existence of
      such regulatory B cells in humans, these findings not only resolve previously
      unexplained contradictions with respect to the outcome of B cell-depleting
      therapy but also provide insight into the best regimen for this treatment
      approach.

PMID- 18802485
TI  - Novel epitope begets a novel pathway in type 1 diabetes progression.
AB  - While CD8+ T cells are critical to diabetogenesis in NOD mice, evidence of their
      involvement in human type 1 diabetes (T1D) has been circumstantial. The existence
      of CD8+ T cells specific for beta cell peptides has been demonstrated, but
      functional data regarding the role of these cells in T1D have been lacking. In
      this issue of the JCI, Skowera et al. describe an unusual self-peptide epitope
      derived from the leader sequence of preproinsulin (PPI) and show that 50% of HLA
      A2+ patients with new-onset T1D possessed circulating CD8+ T cells specific for
      this epitope, suggesting that PPI plays a critical role in the development of T1D
      (see the related article beginning on page 3390). They also report that beta
      cells upregulate PPI expression in the presence of high glucose levels, rendering
      these cells more susceptible to lysis and potentially accelerating disease. This
      suggests that interventions aimed at decreasing the PPI-specific CD8+ T cell
      response early after T1D diagnosis may be efficacious in ameliorating the disease
      process.

PMID- 18802486
TI  - Prenatal maternal diet affects asthma risk in offspring.
AB  - Recently, epigenetic-mediated mechanisms - which involve heritable changes in
      gene expression in the absence of alterations in DNA sequences - have been
      proposed as contributing to asthma. In this issue of the JCI, Hollingsworth and
      colleagues report on the effect of prenatal maternal dietary intake of methyl
      donors on the risk of allergic airway disease in offspring in mice and show that
      these effects involve epigenetic regulation (see the related article beginning on
      page 3462). Supplementation of the maternal diet with methyl donors was
      associated with greater airway allergic inflammation and IgE production in F1
      and, to some extent, F2 progeny. Site-specific differences in DNA methylation and
      reduced transcriptional activity were detected. If these findings are confirmed,
      a new paradigm for asthma pathogenesis may be emerging.

PMID- 18802487
TI  - Hedgehog signaling in biliary fibrosis.
AB  - Congenital and acquired diseases of the biliary tree, or cholangiopathies,
      represent a significant source of morbidity and mortality in both children and
      adults. In late stages of the disease, cholangiocytes can no longer proliferate,
      resulting in loss of bile ducts, increased fibrosis, and ultimately cirrhosis and
      liver failure. Epithelial-mesenchymal transition has been proposed as a potential
      mechanism underlying both cholangiocyte proliferation and fibrogenesis in biliary
      diseases. In this issue of the JCI, using a myofibroblast-cholangiocyte coculture
      system and genetically modified mice, Omenetti and colleagues present evidence
      supporting the importance of paracrine hedgehog signaling between the two cell
      types and increased expression of mesenchymal markers in cholangiocytes (see the
      related article beginning on page 3331). These findings set the stage for future
      studies to further investigate the contribution of hedgehog signaling in both
      cholangiocyte repair and fibrogenesis in biliary diseases.

PMID- 18802488
TI  - Toward a broadly protective influenza vaccine.
AB  - The current inactivated influenza virus vaccines induce antibodies that protect
      against closely related virus strains. They do not, however, protect against
      antibody-escape variants of seasonal influenza A viruses or new pandemic
      influenza A viruses emerging from non-human reservoirs. Might boosting influenza
      A virus-specific CD8+ T cell memory diminish the danger posed by these variant
      viruses? Pre-existing CD8+ T cell-mediated immunity directed at peptides from
      conserved internal proteins of the influenza A virus does not prevent infection,
      but it can promote early virus clearance and decrease morbidity in mice. In this
      issue of the JCI, Lee et al. show that people who have not been exposed to avian
      influenza A (H5N1) viruses have cross-reactive CD8+ T cell memory to a wide range
      of H5N1 peptides (see the related article beginning on page 3478). These peptides
      could be used to add a CD8+ T cell component to current antibody-focused vaccine
      strategies with a view to reducing the impact of infection with novel influenza A
      viruses.

PMID- 18802489
TI  - Tracing the molecular pathogenesis of antiphospholipid syndrome.
AB  - Fetal loss induced by antiphospholipid antibodies (aPLs) in mice is a complement
      driven inflammatory condition. Engagement of the complement receptor C5aR on
      neutrophils induces expression of the principal initiator of the blood clotting
      mechanism, tissue factor (TF), and blocking this downstream event of complement
      activation prevents antibody-induced fetal loss. In this issue of the JCI, the
      study by Redecha et al. clarifies that in mice, the contribution of TF to this
      pathogenic mechanism is independent of its role in coagulation and thrombosis,
      but involves inflammatory signaling through the receptor PAR2 (see the related
      article beginning on page 3453). The study not only sheds light on a critical
      effector mechanism of aPL-induced fetal loss, but also suggests that treatment
      with statins, which decrease TF and PAR2 expression, may hold promise as a
      therapeutic approach to antiphospholipid syndrome-associated pregnancy
      complications.

PMID- 18802490
TI  - Biology of HIV mucosal transmission.
AB  - PURPOSE OF REVIEW: HIV-1 mucosal transmission plays a critical role in HIV-1
      infection and AIDS pathogenesis. This review summarizes the latest advances in
      biological studies of HIV-1 mucosal transmission, highlighting the implications
      of these studies in the development of microbicides to prevent HIV-1
      transmission. RECENT FINDINGS: New studies of initial HIV-1 infection using
      improved culture models updated the current view of mucosal transmission.
      Mechanistic studies enhanced our understanding of cell-cell transmission of HIV-1
      mediated by the major target cells, including dendritic cells, CD4(+) T cells,
      and macrophages. Increasing evidence indicated the significance of host factors
      and immune responses in HIV-1 mucosal infection and transmission. SUMMARY: Recent
      progress in HIV-1 mucosal infection and transmission enriches our knowledge of
      virus-host interactions and viral pathogenesis. Functional studies of HIV-1
      interactions with host cells can provide new insights into the design of more
      effective approaches to combat HIV-1 infection and AIDS.

PMID- 18802491
TI  - Fabrication and Manipulation of Ionotropic Hydrogels Crosslinked by Paramagnetic
      Ions.
AB  - This manuscript describes the fabrication and manipulation of millimeter-scale
      spheres fabricated from ionotropic hydrogels that are crosslinked with
      paramagnetic metal ions (e.g., Ho(3+)). These ionotropic hydrogels experience a
      force in a magnetic field gradient that correlates with the concentration of the
      paramagnetic cations crosslinking the polymer. In an externally applied magnetic
      field, the paramagnetic hydrogel spheres assemble into ordered arrays or confined
      geometrical structures in the regions of highest magnetic field. These spheres
      can be separated from heterogeneous mixtures of diamagnetic materials using a
      simple bar magnet. Two applications using these recoverable hydrogel spheres were
      demonstrated: i) When prepared with embedded indicator dyes bound to paper, the
      spheres were used as colorimetric sensors for pH. ii) When prepared with embedded
      activated carbon powder, they were used to remove organic materials from aqueous
      solutions.

PMID- 18802492
TI  - The curious case of competition in Spanish speech production.
AB  - In previous studies in English examining the influence of phonological
      neighbourhood density in spoken word production, words with many similar sounding
      words, or a dense neighbourhood, were produced more quickly and accurately than
      words with few similar sounding words, or a sparse neighbourhood. The influence
      of phonological neighbourhood density on the process of spoken word production in
      Spanish was examined with a picture-naming task. The results showed that pictures
      with Spanish names from sparse neighbourhoods were named more quickly than
      pictures with Spanish names from dense neighbourhoods. The present pattern of
      results is the opposite of what has been previously found in speech production in
      English. We hypothesise that differences in the morphology of Spanish and English
      and/or the location in the word where phonological neighbours tend to occur may
      contribute to the processing differences observed in the two languages.

PMID- 18802493
TI  - High-numerical-aperture-based virtual point detectors for photoacoustic
      tomography.
AB  - The focal point of a high-numerical-aperture (NA) ultrasonic transducer can be
      used as a virtual point detector. This virtual point detector detects
      omnidirectionally over a wide acceptance angle. It also combines a large active
      transducer surface and a small effective virtual detector size. Thus the
      sensitivity is high compared with that of a real point detector, and the aperture
      effect is small compared with that of a finite size transducer. We present two
      kinds of high-NA-based virtual point detectors and their successful application
      in photoacoustic tomography. They can also be applied in other ultrasound-related
      fields.

PMID- 18802494
TI  - Sulforhodamine Adsorbed Langmuir-Blodgett Layers on Silver Island Films: Effect
      of Probe Distance on the Metal-Enhanced Fluorescence.
AB  - Metal-Enhanced Fluorescence (MEF) has become an important method in biomedical
      sensing. In this paper, we present the distance-dependent MEF of sulforhodamine B
      (SRB) monolayer on silver island films (SIFs). SRB is electrostatically
      incorporated into the Langmuir-Blodgett (LB) layers of octadecylamine (ODA)
      deposited on glass and SIFs substrates. The distances between SRB and SIFs or
      glass surfaces are controlled by depositing a varied number of inert stearic acid
      (SA) spacer layers. SRB is incorporated into positively charged LB layers of ODA
      by immersing the ODA deposited substrates into aqueous solution of SRB. Dye
      incorporated ODA layers with 10 nm separation distance from the SIFs surface show
      maximum metal-enhanced fluorescence intensity; ~7-fold increase in intensity as
      compared to that from the glass surface. The corresponding enhancement factor is
      reduced with increasing or decreasing the probe distance from the SIFs surface.
      Additionally, SRB on SIF surfaces show reduced lifetimes. We observed the
      shortest lifetime from the SRB with 5 nm distance from the SIF surfaces and the
      lifetime increased consistently with increasing the distances between the
      fluorophore and the SIFs surface. These observed spectral changes, increase in
      fluorescence intensity and decreased fluorescence lifetimes, are in accordance
      with the expected effects due to near-field interactions between the silver
      nanoparticles and fluorophores. We have also analyzed the complex fluorescence
      heterogeneous decays on metallic nanostructured surfaces using continuous
      distributions of decay times. The decay-time distributions appear to be sensitive
      to the distance between the metal and fluorophore and represent the underlying
      heterogeneity of the samples. The present systematic study provides significant
      information on the effect of fluorophore distance on the metal-enhanced
      fluorescence phenomenon.

PMID- 18802495
TI  - Polarizable empirical force field for the primary and secondary alcohol series
      based on the classical Drude model.
AB  - A polarizable empirical force field based on the classical Drude oscillator has
      been developed for the aliphatic alcohol series. The model is optimized with
      emphasis on condensed-phase properties and is validated against a variety of
      experimental data. Transferability of the developed parameters is emphasized by
      the use of a single electrostatic model for the hydroxyl group throughout the
      alcohol series. Aliphatic moiety parameters were transferred from the polarizable
      alkane parameter set, with only the Lennard-Jones parameters on the carbon in
      methanol optimized. The developed model yields good agreement with pure solvent
      properties with the exception of the heats of vaporization of 1-propanol and 1
      butanol, which are underestimated by approximately 6%; special LJ parameters for
      the oxygen in these two molecules that correct for this limitation are presented.
      Accurate treatment of the free energies of aqueous solvation required the use of
      atom-type specific O(alcohol)-O(water) LJ interaction terms, with specific terms
      used for the primary and secondary alcohols. With respect to gas phase properties
      the polarizable model overestimates experimental dipole moments and quantum
      mechanical interaction energies with water by approximately 10 and 8 %,
      respectively, a significant improvement over 44 and 46 % overestimations of the
      corresponding properties in the CHARMM22 fixed-charge additive model. Comparison
      of structural properties of the polarizable and additive models for the pure
      solvents and in aqueous solution shows significant differences indicating atomic
      details of intermolecular interactions to be sensitive to the applied force
      field. The polarizable model predicts pure solvent and aqueous phase dipole
      moment distributions for ethanol centered at 2.4 and 2.7 D, respectively, a
      significant increase over the gas phase value of 1.8 D, whereas in a solvent of
      lower polarity, benzene, a value of 1.9 is obtained. The ability of the
      polarizable model to yield changes in dipole moment as well as the reproduction
      of a range of condensed phase properties indicates its utility in the study of
      the properties of alcohols in a variety of condensed phase environments as well
      as representing an important step in the development of a comprehensive force
      field for biological molecules.

PMID- 18802497
TI  - Increasing Memory Self-Efficacy and Strategy Use in Hispanic Elders.
AB  - This study tested the effects of a 4-week, nine-session group intervention taught
      in Spanish to Hispanic older adults entitled "Quieres Mejorar Tu Memoria" (Do you
      wish to improve your memory?). The program was based on Bandura's self-efficacy
      theory and was designed to increase memory self-efficacy and strategy use. A
      total of 33 older adults attending a senior center (mean--age = 69 years;
      education = 5 years; MMSE = 25) participated in the study. A booster session and
      a post-test were given at 3 months to the intervention group (n=22). At posttest
      the intervention reported greater confidence in preventing decline in their
      memories, and in particular greater use of the internal strategy of elaboration
      (2.99 vs. 3.41), and the external strategies of list (2.55 vs. 3.38) and note
      (3.27 vs. 3.75).

PMID- 18802496
TI  - Memory T cells established by seasonal human influenza A infection cross-react
      with avian influenza A (H5N1) in healthy individuals.
AB  - The threat of avian influenza A (H5N1) infection in humans remains a global
      health concern. Current influenza vaccines stimulate antibody responses against
      the surface glycoproteins but are ineffective against strains that have undergone
      significant antigenic variation. An alternative approach is to stimulate pre
      existing memory T cells established by seasonal human influenza A infection that
      could cross-react with H5N1 by targeting highly conserved internal proteins. To
      determine how common cross-reactive T cells are, we performed a comprehensive ex
      vivo analysis of cross-reactive CD4+ and CD8+ memory T cell responses to
      overlapping peptides spanning the full proteome of influenza A/Viet Nam/CL26/2005
      (H5N1) and influenza A/New York/232/2004 (H3N2) in healthy individuals from the
      United Kingdom and Viet Nam. Memory CD4+ and CD8+ T cells isolated from the
      majority of participants exhibited human influenza-specific responses and showed
      cross-recognition of at least one H5N1 internal protein. Participant CD4+ and
      CD8+ T cells recognized multiple synthesized influenza peptides, including
      peptides from the H5N1 strain. Matrix protein 1 (M1) and nucleoprotein (NP) were
      the immunodominant targets of cross-recognition. In addition, cross-reactive CD4+
      and CD8+ T cells recognized target cells infected with recombinant vaccinia
      viruses expressing either H5N1 M1 or NP. Thus, vaccine formulas inducing
      heterosubtypic T cell-mediated immunity may confer broad protection against avian
      and human influenza A viruses.

PMID- 18802498
TI  - VOCALIZATIONS AND ASSOCIATED BEHAVIORS OF THE SOMBRE HUMMINGBIRD (APHANTOCHROA
      CIRRHOCHLORIS) AND THE RUFOUS-BREASTED HERMIT (GLAUCIS HIRSUTUS).
AB  - Vocal behavior in tropical hummingbirds is a new area of study. Here, we present
      findings on the vocalizations and associated behaviors of two species: Sombre
      Hummingbird (Aphantochroa cirrhochloris) and Rufous-breasted Hermit (Glaucis
      hirsutus). These are the only hummingbirds in which the brain areas activated by
      singing have been demonstrated. They are also among the basal species of their
      respective subfamilies, Trochilinae and Phaethornithinae and, thus, represent
      early stages in the evolution of hummingbird vocal communication. We found that
      the two species exhibit distinctive vocalizations and behaviors. Sombre
      Hummingbird calls had more modulation and were often used during agonistic
      interactions, whereas Rufous-breasted Hermit calls had higher pitch and purer
      tones and were produced in less aggressive interactions. Sombre Hummingbird song
      was highly stereotyped in syllable structure and syntax, whereas Rufous-breasted
      Hermit song was highly variable. Comparative analysis points to consistent
      similarities in use of vocalizations by the Sombre Hummingbird and other
      trochilines, and by the Rufous-breasted Hermit and other phaethornithines. We
      hypothesize that differences in vocal behavior between hummingbird lineages arise
      as adaptations to their foraging strategies.

PMID- 18802499
TI  - Revealing Dimensions of Thinking in Open-Ended Self-Descriptions: An Automated
      Meaning Extraction Method for Natural Language.
AB  - A new method for extracting common themes from written text is introduced and
      applied to 1,165 open-ended self-descriptive narratives. Drawing on a lexical
      approach to personality, the most commonly-used adjectives within narratives
      written by college students were identified using computerized text analytic
      tools. A factor analysis on the use of these adjectives in the self-descriptions
      produced a 7-factor solution consisting of psychologically meaningful dimensions.
      Some dimensions were unipolar (e.g., Negativity factor, wherein most loaded items
      were negatively valenced adjectives); others were dimensional in that
      semantically opposite words clustered together (e.g., Sociability factor, wherein
      terms such as shy, outgoing, reserved, and loud all loaded in the same
      direction). The factors exhibited modest reliability across different types of
      writ writing samples and were correlated with self-reports and behaviors
      consistent with the dimensions. Similar analyses with additional content words
      (adjectives, adverbs, nouns, and verbs) yielded additional psychological
      dimensions associated with physical appearance, school, relationships, etc. in
      which people contextualize their self-concepts. The results suggest that the
      meaning extraction method is a promising strategy that determines the dimensions
      along which people think about themselves.

PMID- 18802500
TI  - Fragmentation of doubly-protonated peptide ion populations labeled by H/D
      exchange with CD(3)OD.
AB  - Doubly-protonated bradykinin (RPPGFSPFR) and an angiotensin III analogue
      (RVYIFPF) were subjected to hydrogen/deuterium (H/D) exchange with CD(3)OD in a
      Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometer. A bimodal
      distribution of deuterium incorporation was present for bradykinin after H/D
      exchange for 90 s at a CD(3)OD pressure of 4 x 10(-7) Torr, indicating the
      existence of at least two distinct populations. Bradykinin ion populations
      corresponding to 0-2 and 5-11 deuteriums (i.e., D(0), D(1), D(2), D(5), D(6),
      D(7), D(8), D(9), D(10), and D(11)) were each monoisotopically selected and
      fragmented via sustained off-resonance irradiation (SORI) collision-induced
      dissociation (CID). The D(0)-D(2) ion populations, which correspond to the slower
      exchanging population, consistently require lower SORI amplitude to achieve a
      similar precursor ion survival yield as the faster-reacting (D(5)-D(11))
      populations. These results demonstrate that conformation/protonation motif has an
      effect on fragmentation efficiency for bradykinin. Also, the partitioning of the
      deuterium atoms into fragment ions suggests that the C-terminal arginine residue
      exchanges more rapidly than the N-terminal arginine. Total deuterium
      incorporation in the b(1)/y(8) and b(2)/y(7) ion pairs matches very closely the
      theoretical values for all ion populations studied, indicating that the ions of a
      complementary pair are likely formed during the same fragmentation event, or that
      no scrambling occurs upon SORI. Deuterium incorporation into the y(1)/a(8) pseudo
      ion pair does not closely match the expected theoretical values. The other
      peptide, doubly-protonated RVYIFPF, has a trimodal distribution of deuterium
      incorporation upon H/D exchange with CD(3)OD at a pressure of 1 x 10(-7) Torr for
      600 s, indicating at least three distinct ion populations. After 90 s of H/D
      exchange where at least two distinct populations are detected, the D(0)-D(7) ion
      populations were monoisotopically selected and fragmented via SORI-CID over a
      range of SORI amplitudes. The precursor ion survival yield as a function of SORI
      amplitude falls into two distinct behaviors corresponding to slower- and faster
      reacting ion populations. The slower-reacting population requires larger SORI
      amplitudes to achieve the same precursor ion survival yield as the faster
      exchanging population. Total deuterium incorporation into the y(2)/b(5) ion pairs
      matches closely the theoretical values over all ion populations and SORI
      amplitudes studied. This result indicates the y(2) and b(5) ions are likely
      formed by the same mechanism over the SORI amplitudes studied.

PMID- 18802501
TI  - Binaphthol-derived phosphoric acid as a versatile catalyst for enantioselective
      carbon-carbon bond forming reactions.
AB  - Binaphthol-derived monophosphoric acids have been designed as novel chiral
      Bronsted-acid catalysts. The chiral phosphoric acids thus developed function as
      efficient enantioselective catalysts for a variety of organic transformations,
      especially for carbon-carbon bond forming reactions.

PMID- 18802502
TI  - Dinuclear chiral vanadium catalysts for oxidative coupling of 2-naphthols via a
      dual activation mechanism.
AB  - This review describes our recent efforts in the development of chiral dinuclear
      vanadium complexes that work as dual activation catalysts for the oxidative
      coupling of 2-naphthols. The dinuclear vanadium(iv) complex (R(a),S,S)- was
      prepared by complexation of VOSO(4) with the Schiff base derived from (R)-3,3'
      diformyl-2,2'-dihydroxy-1,1'-binaphthyl () and (S)-tert-leucine. Since the
      dinuclear vanadium(iv) complex was found to be readily oxidized to afford a
      corresponding vanadium(v) species during preparation in air, a new synthetic
      procedure using VOCl(3) has been applied towards dinuclear vanadium(v) complexes
      (R(a),S,S)- and (R(a),S,S)-. To the best of our knowledge, (R(a),S,S)-, and show
      considerably higher catalytic activity than previously reported vanadium
      complexes for the oxidative coupling of 2-naphthols.

PMID- 18802503
TI  - Dendron-based model systems for flavoenzyme activity: towards a new class of
      synthetic flavoenzyme.
AB  - Three generations of water-soluble flavin dendrons have been synthesized and the
      role dendrimer generation has on the physical and catalytic properties of these
      assemblies has been investigated.

PMID- 18802504
TI  - Model systems for flavoenzyme activity: intramolecular self-assembly of a flavin
      derivative via hydrogen bonding and aromatic interactions.
AB  - We have synthesised a flavin derivative incorporating functionalities that
      promote intramolecular self-assembly via hydrogen bonding and aromatic
      interactions.

PMID- 18802505
TI  - Unilamellar composite vesicles and Y-junctions from pristine fullerene C(60).
AB  - We report here the first structurally defined aqueous phase nanovesicles and Y
      junctions from a pristine C(60) dispersion at a strictly defined [C(60)]/[TX-100]
      concentration ratio, bearing a temporal dependence.

PMID- 18802506
TI  - Is catenation beneficial for hydrogen storage in metal-organic frameworks?
AB  - Grand canonical Monte Carlo (GCMC) simulations demonstrate that catenation can be
      beneficial for improving hydrogen storage in metal-organic frameworks at
      cryogenic temperatures and low pressures but not necessarily at room temperature.

PMID- 18802507
TI  - Carborane-based metal-organic frameworks as highly selective sorbents for CO(2)
      over methane.
AB  - Separation of CO(2)/CH(4) mixtures was studied in carborane-based metal-organic
      framework materials with and without coordinatively unsaturated metal sites; high
      selectivities for CO(2) over CH(4) ( approximately 17) are obtained, especially
      in the material with open metal sites.

PMID- 18802508
TI  - Click chemistry step growth polymerization of novel alpha-azide-omega-alkyne
      monomers.
AB  - A novel step growth polymerization A-B strategy based on the click chemistry
      polyaddition of tailor-made alpha-azide-omega-alkyne low molar mass monomers was
      developed, leading to polytriazole (co)polymers with tunable structures and
      properties.

PMID- 18802509
TI  - Multiple molecular logic functions and molecular calculations facilitated by
      surfactant's versatility.
AB  - Two isomeric compounds and , combining intramolecular charge transfer (ICT) and
      photoinduced electron transfer (PET) mechanisms together, were designed and used
      as logic gates with configurable multiple outputs; ten different logic functions
      (AND, NAND, OR, NOR, XNOR, INHIBIT, YES, NO, PASS 1 and PASS 0) were achieved by
      varying the inputs threshold or by altering the inputs; furthermore, half
      addition and half subtraction were performed within (or ); the concept
      demonstrated here may provide a strategy for constructing more integrated
      molecular level devices with multiple functions.

PMID- 18802510
TI  - Engineering tandem modular protein based reversible hydrogels.
AB  - We report the engineering of the first tandem modular protein based hydrogel that
      exhibits unique properties combining low erosion rate, fast and reversible sol
      gel transition and antibody binding ability.

PMID- 18802511
TI  - In tube determination of the absolute configuration of alpha- and beta-hydroxy
      acids by NMR via chiral BINOL borates.
AB  - A simple NMR methodology, through the formation of chiral BINOL borates in the
      NMR tube, and that reunites the advantages of chiral derivatizing (CDAs) and
      chiral solvating agents (CSAs), is presented for the assignment of the absolute
      configuration of alpha- and beta-hydroxy acids.

PMID- 18802512
TI  - Lactonizations of carboxylic acid-substituted 3-fluorodihydropyridines with
      electrophiles: peculiar behaviour of F(+).
AB  - Whereas for 3-fluorodihydropyridine-substituted carboxylic acids electrophiles
      such as HCl, iodine, bromine and peracids discriminate the double bond lacking
      and that bearing fluorine, no such differentiation took place in the case of
      electrophilic fluorine since the formation of both mono and gem-difluorolactones
      took place.

PMID- 18802513
TI  - State-resolved UV photofragmentation spectrum of the metal dication complex
      [Zn(pyridine)(4)](2+).
AB  - A combined theoretical and experimental study of electronic transitions in the
      complex [Zn(pyridine)(4)](2+) provides the first example of a state-resolved
      electronic spectrum to be recorded for a dication complex in the gas phase.

PMID- 18802514
TI  - Low reactivity of non-bridging oxygen defects on stoichiometric silica surfaces.
AB  - Using ab initio molecular dynamics simulations we demonstrate that surfaces of
      stoichiometric silica exhibiting non-bridging oxygen defects can be surprisingly
      resistant to attack by water.

PMID- 18802515
TI  - Controlled generation of acentric and homochiral coordination compounds from a
      versatile asymmetric ligand 4-(1H-1,2,4-triazol-3-yl)-4H-1,2,4-triazole.
AB  - Luminescent acentric and homochiral coordination compounds, which possess new
      topological networks, multiple helical structures and NLO properties, have been
      generated through the control of a versatile asymmetric ligand as well as
      inorganic anions, and this suggests a new protocol for preparing acentric and
      chiral materials.

PMID- 18802516
TI  - Towards understanding phosphonoacetaldehyde hydrolase: an alternative mechanism
      involving proton transfer that triggers P-C bond cleavage.
AB  - The theoretical QM/MM study of the reaction catalysed by phosphonoacetaldehyde
      hydrolase indicates a possible alternative mechanism of the P-C bond cleavage: as
      opposed to the mechanism proposed earlier and that involved formation of a
      covalently bound intermediate (Schiff-base), in the new mechanism, the bond
      breaking process is facilitated by proton transfer from catalytic lysine residue
      to the substrate.

PMID- 18802517
TI  - Trapping Pd(0) in nanoparticle-assembled microcapsules: an efficient and reusable
      catalyst.
AB  - Pd nanoparticles dually encased by soft (polyamine) and hard (silica) materials
      in a microcapsule structure, obtained via a nanoparticle self-assembly method,
      exhibit excellent catalytic activity, with efficient catalyst recovery and
      reusability.

PMID- 18802518
TI  - Controlled formation of porous magnetic nanorods via a liquid/liquid solvothermal
      method.
AB  - Porous magnetic nanorods with sizes readily modulated and high water affinity are
      prepared via a water-in-oil/water solvothermal method.

PMID- 18802519
TI  - Fabrication of mesoporous Pt nanotubes utilizing dual templates under a reduced
      pressure condition.
AB  - Pt nanotubes with mesoporous walls have been successfully prepared for the first
      time by the combination of hard templates (porous anodic alumina membranes, PAAM)
      and soft templates (lyotropic liquid crystals, LLC).

PMID- 18802520
TI  - Dynamic resolution of N-Boc-2-lithiopiperidine.
AB  - Dynamic thermodynamic resolution of N-Boc-2-lithiopiperidine is possible using a
      chiral ligand; the two enantiomers of this organolithium can be resolved with
      selectivities of up to 85 : 15 from a selection of 26 chiral diamino-alkoxide
      ligands screened.

PMID- 18802521
TI  - A diastereo- and enantioselective synthesis of alpha-substituted anti-alpha,beta
      diaminophosphonic acid derivatives.
AB  - Highly diastereo- and enantioselective additions of alpha-nitrophosphonates to
      imines catalyzed by a chiral Bronsted acid are described.

PMID- 18802522
TI  - Translocation of copper within the cavity of cryptands: reversible fluorescence
      signaling.
AB  - The movement of a copper ion inside the cavity of cryptands having two distinct
      metal binding sites at each end is linked to a fluorescence ON-OFF process in a
      reversible manner, providing a new way of fluorescence switching.

PMID- 18802523
TI  - Facile one pot synthesis of a range of reversible addition-fragmentation chain
      transfer (RAFT) agents.
AB  - The application of a universal synthetic strategy for the high yielding and
      facile synthesis of a wide range of functional RAFT agents including
      trithiocarbonates, xanthates and dithiocarbamates is described.

PMID- 18802524
TI  - Highly dispersed clay-polyolefin nanocomposites free of compatibilizers, via the
      in situ polymerization of alpha-olefins by clay-supported catalysts.
AB  - In situ polymerization by certain transition metal catalysts supported on and
      activated by acid-treated montmorillonite produces well-dispersed clay-polyolefin
      nanocomposites, without requiring either organic surfactants to be present in the
      clay phase or modification of the polyolefin structure.

PMID- 18802525
TI  - From dioxime oxalates to dihydropyrroles and phenanthridines via iminyl radicals.
AB  - Dioxime oxalates are useful precursors for the clean generation of iminyl
      radicals by sensitised UV photolysis and can be adapted for serviceable
      preparations of 3,4-dihydro-2H-pyrroles and phenanthridines.

PMID- 18802526
TI  - Catalytic properties of MIL-101.
AB  - A very high catalytic activity in the cyanosilylation reaction was observed for
      MIL-101, a chromium based metal-organic framework; moreover, MIL-101 is also a
      remarkably stable support for palladium in hydrogenation reactions, with
      significantly higher activity than e.g. palladium on activated carbon.

PMID- 18802527
TI  - Reactions of iridium hydride pincer complexes with dioxygen: new dioxygen
      complexes and reversible O2 binding.
AB  - The reaction of molecular oxygen with iridium pincer hydride complexes,
      ((tBu)PCP)Ir(H)(X) [(tBu)PCP = kappa(3)-C(6)H(3)(CH(2)P(t)Bu(2))(2), X = Ph, H,
      CCPh], results in O(2) induced reductive elimination and formation of the novel
      dioxygen complexes ((tBu)PCP)Ir(O(2))(n) [n = 1 (), 2 ()].

PMID- 18802528
TI  - Palladium-catalyzed reaction of allyl halides with alpha-diazocarbonyl compounds.
AB  - The Pd(OAc)(2)-catalyzed reaction between alpha-diazocarbonyl compounds and allyl
      bromides or chlorides leads to the formation of 1,3-diene derivatives.

PMID- 18802529
TI  - Supported ionic liquid phase catalysis on functionalized carbon nanotubes.
AB  - Highly active rhodium catalysts have been prepared by immobilization of an ionic
      liquid film on carbon nanotubes functionalized with imidazolium-based ionic
      moieties.

PMID- 18802530
TI  - Methylidynearsine (HC[triple bond]As): synthesis and direct characterization by
      UV-photoelectron spectroscopy and mass spectrometry.
AB  - The dehydrohalogenation of gaseous dichloromethylarsine on solid base led to
      chloromethylidenearsine and, at higher temperature of the base, to
      methylidynearsine, the third unsubstituted heteroalkyne unambiguously synthesized
      up to now.

PMID- 18802531
TI  - Metal-free Michael addition initiated multicomponent oxidative cyclodehydration
      route to polysubstituted pyridines from 1,3-dicarbonyls.
AB  - A simple metal-free, step-economic and selective access to pyridines from readily
      available substrates is reported, involving a flexible 4 A molecular sieves
      promoted Michael addition initiated domino three-component reaction between a 1,3
      dicarbonyl, a Michael acceptor and a synthetic equivalent of ammonia.

PMID- 18802532
TI  - Enhanced stability of charged dendrimer-encapsulated Pd nanoparticles in ionic
      liquids.
AB  - Highly stable dendrimer-encapsulated Pd nanoparticles in ionic liquids were
      prepared for the first time by using charged PAMAM dendrimers as templates, which
      could maintain hydrogenation efficiency for up to at least 12 recycles.

PMID- 18802533
TI  - Facile approach to prepare loose-packed NiO nano-flakes materials for
      supercapacitors.
AB  - The nickel oxide nano-flakes materials prepared by a facile approach maintain
      high power density at high rates of discharge and have excellent cycle life,
      suggesting their potential application in supercapacitors.

PMID- 18802534
TI  - Bronsted acid catalyzed regioselective aza-Ferrier reaction: a novel synthetic
      method for alpha-(N-Boc-2-pyrrolidinyl) aldehydes.
AB  - The 1,4-elimination reaction of (Z)-N-Boc-2-(4-methoxy-2-alkenyloxy)pyrrolidines
      is shown to proceed with high (1E,3E)-stereoselectivity to afford N-Boc-2-(1,3
      dienyloxy)pyrrolidines; the Bronsted acid catalyzed aza-Ferrier reaction of the N
      Boc-2-(1,3-dienyloxy)pyrrolidines (3) provides alpha-(N-Boc-2-pyrrolidinyl)
      aldehydes in excellent yields with high alpha-regioselectivities.

PMID- 18802535
TI  - Chemogenetic protein engineering: an efficient tool for the optimization of
      artificial metalloenzymes.
AB  - Artificial metalloenzymes, based on the incorporation of a catalytically active
      organometallic moiety within a host protein, lie at the interface between
      organometallic and enzymatic catalysis. In terms of activity, reaction
      repertoire, substrate range and operating conditions, they take advantage of the
      versatility of the organometallic chemistry. In contrast, the enantioselectivity
      is determined by the biomolecular scaffold, which provides a well defined second
      coordination sphere to the organometallic moiety, reminiscent of enzymes. The
      attractive feature of such systems is their optimization potential, which
      combines chemical and genetic methods (i.e. chemogenetic) to screen diversity
      space. This feature article describes the implementation of such an optimization
      protocol for artificial transfer hydrogenases, for which we have the most
      detailed understanding.

PMID- 18802536
TI  - Activatable imaging probes with amplified fluorescent signals.
AB  - Current optical imaging probe applications are hampered by poor sensitivity and
      specificity to the target, but molecular-level fluorescent signal activation
      strategies can efficiently overcome these limitations. Recent interdisciplinary
      research that couples the imaging sciences to fluorophore, peptide, polymer, and
      inorganic-based chemistry has generated novel imaging probes that exhibit high
      sensitivity and low background noise in both in vitro and in vivo applications.
      This feature article introduces and discusses the various approaches described by
      the term "fluorescent signal activation methods" with respect to their unique
      imaging probe design strategies and applications.

PMID- 18802537
TI  - Enantioselective regulation of a metal complex in reversible binding to serum
      albumin: dynamic helicity inversion signalled by circularly polarised
      luminescence.
AB  - The helicity of the (SSS)-Delta enantiomer of a terbium and europium(III) complex
      is inverted on reversible binding to 'drug site II' of serum albumin, signalled
      by a switch in its circularly polarised emission; no such behaviour occurs with
      the (RRR)-Lambda complexes, thereby defining a unique chiroptical probe of
      albumin binding.

PMID- 18802538
TI  - Binary stacks of [CuC6F5]4 with arenes.
AB  - Formation of the first binary stacks of an intact organocopper aggregate with the
      arenes naphthalene and 2,2'-bithiophene is reported; crystallographic data
      suggest that the supramolecular assembly process is supported by Cu-pi, Cu-S, and
      perfluoroarene-arene pi-interactions.

PMID- 18802539
TI  - Proton-coupled electron transfer from a luminescent excited state.
AB  - A luminescent cationic iridium complex with a 2,2'-biimidazole ligand forms
      hydrogen-bonded 1 : 1 adducts with benzoate anions; photoexcitation of the metal
      complex in presence of 3,5-dinitrobenzoate triggers a proton-coupled electron
      transfer.

PMID- 18802540
TI  - Sequence-specifically platinum metal deposition on enzymatically synthesized DNA
      block copolymer.
AB  - Platinum metal was sequence-specifically deposited on the DNA block copolymer
      synthesized by the Klenow fragment of E. coli DNA polymerase I (3'-5' exonuclease
      deficient).

PMID- 18802541
TI  - Directing single-walled carbon nanotubes to self-assemble at water/oil interfaces
      and facilitate electron transfer.
AB  - Both the behavior and the general key factors for assembling flexible SWNT films
      at the water/oil interface were investigated; the electron transfer, one of the
      most fundamental chemical processes, at the SWNT-sandwiched water/oil interface
      was also firstly illustrated using scanning electrochemical microscopy.

PMID- 18802542
TI  - Molecular orientation transition of organic thin films on graphite: the effect of
      intermolecular electrostatic and interfacial dispersion forces.
AB  - In situ low-temperature scanning tunnelling microscopy investigation reveals a
      molecular orientation transition of organic thin films of pentacene and p
      sexiphenyl on graphite, arising from the delicate balance between the
      intermolecular electrostatic and interfacial dispersion forces.

PMID- 18802543
TI  - Facile fabrication of conducting polymer hydrogels via supramolecular self
      assembly.
AB  - We describe a simple and versatile method to fabricate conducting polymer
      hydrogels via supramolecular self-assembly between polymers and multivalent
      cations; the as-prepared hydrogels are potentially applicable in the fields of
      electrosensors, chemical release and artificial muscles.

PMID- 18802544
TI  - Gold mediated glycosylations: selective activation of propargyl 1,2-orthoesters
      in the presence of aglycones containing a propargyl moiety.
AB  - Selective activation of propargyl 1,2-orthoesters in the presence of propargyl
      glycosides and propargyl ethers was studied; a catalytic amount of AuBr3
      activated the propargyloxy group of the 1,2-orthoester thereby giving access to
      disaccharides with the propargyl group at the reducing end; furthermore,
      propargyl ethers were unaffected under the reaction conditions.

PMID- 18802545
TI  - Diol-substituted boron complexes of dipyrrolyl diketones as anion receptors and
      covalently linked 'pivotal' dimers.
AB  - Diol-substitution at a boron unit results in the formation of anion receptors
      consisting of dipyrrolyl diketones and covalently linked dimers, which exhibit
      selective binding for dianions with appropriate lengths.

PMID- 18802546
TI  - Strategic synthesis of SBA-15 nanorods.
AB  - A simple synthesis of homogeneously sized, ordered mesoporous silica nanorods
      (SBA-15), spanning about 10 porous channels in width and ranging from 300 to 600
      nm in length is reported.

PMID- 18802547
TI  - Hydrous zinc halide-catalyzed aminosulfonation of hydrocarbons.
AB  - Benzylic and allylic hydrocarbons are selectively converted to the corresponding
      sulfonamides by a ZnBr2-H2O-catalyzed reaction with PhI=NTs; saturated adamantane
      is aminosulfonated at the tertiary C-H bond.

PMID- 18802548
TI  - B-alkyl Suzuki couplings for the stereoselective synthesis of substituted pyrans.
AB  - Unprotected homoallylic alcohols can be directly converted to cis-2,6
      disubstituted pyrans by palladium catalyzed B-alkyl Suzuki coupling and
      subsequent Michael addition.

PMID- 18802549
TI  - Suzuki cross-coupling reactions on the surface of carbon-coated cobalt: expanding
      the applicability of core-shell nano-magnets.
AB  - To develop magnetic nanomaterials applicable to organic synthesis, the Suzuki
      cross-coupling method was adapted to attach a range of functional groups to
      carbon-coated core-shell materials via commercially-available substituted
      arylboronic acids.

PMID- 18802550
TI  - Cyclopropenyllithiums as a new source of 1,1-bismetalated cyclopropyl
      derivatives.
AB  - The allylmetalation of functionalised cyclopropenyllithium derivatives leads to
      the unique formation of 1,1-bismetalated cyclopropyl species that react
      selectively with different electrophiles.

PMID- 18802551
TI  - B-H activation by frustrated Lewis pairs: borenium or boryl phosphonium cation?
AB  - Catechol borane reacts with the frustrated Lewis pairs tBu2RP (R = tBu, 2
      C6H4(C6H5)) and B(C6F5)3 to give the species [(C6H4O2)BPtBu2R][HB(C6F5)3] that
      can formally be described as either borenium cation or boryl-phosphonium salts;
      the nature of these species was probed with DFT calculations.

PMID- 18802552
TI  - The influence of ethylene glycol chains on the thermodynamics of hydrogen-bonded
      supramolecular assemblies in apolar solvents.
AB  - Substitution of hydrogen bond directed supramolecular assemblies with ethylene
      glycol chains leads to a reduction in the association constant in apolar
      solvents, where the reduction of the association constant is dependent on the
      length of the aliphatic spacer connecting the hydrogen bonds and the ethylene
      glycol chain.

PMID- 18802553
TI  - Lewis base-catalyzed conjugate reduction and reductive aldol reaction of
      alpha,beta-unsaturated ketones using trichlorosilane.
AB  - Lewis bases such as Ph3P=O and HMPA catalyze the 1,4-reduction of alpha,beta
      unsaturated ketones with trichlorosilane, and because the 1,2-reduction of
      aldehydes scarcely proceeded under the conditions, one-pot reductive aldol
      reactions with aldehydes were successfully achieved; preliminary studies using a
      chiral Lewis base revealed a high potential for enantioselective catalysis.

PMID- 18802554
TI  - Silica-supported catalysts for ring-closing metathesis: effects of linker group
      and microenvironment on recyclability.
AB  - The interesting effects of the linker and microenvironment on the recyclability
      of well-defined silica-supported catalysts were examined, which demonstrated the
      excellent activity and reusability for the ring-closing metathesis (RCM) of a
      number of substrates.

PMID- 18802555
TI  - Ni(II)-catalyzed enantioselective Nazarov cyclizations.
AB  - Nazarov cyclizations are catalyzed by a dicationic Ni(II) complex containing the
      chiral tridentate phosphine Pigiphos; the catalyst exerts a high degree of
      torquoselectivity and affords the products in up to 88% ee.

PMID- 18802556
TI  - Subtractive assembly of DNA nanoarchitectures driven by fuel strand displacement.
AB  - Herein we demonstrate that flexible DNA architectures with larger cavities can be
      efficiently constructed by first assembling a relatively more rigid DNA tile
      architecture and subsequently subtracting a center tile through fuel strand
      displacement; such structures are otherwise difficult to obtain if the center
      tile is missing in the beginning, proving a new strategy for DNA self-assembly.

PMID- 18802557
TI  - Chemoenzymatic synthesis of GDP-azidodeoxymannoses: non-radioactive probes for
      mannosyltransferase activity.
AB  - GDP-2-, 3-, 4- or 6-azidomannoses can be successfully prepared from the
      corresponding azidomannose-1-phosphates and GTP using the enzyme GDP
      Mannosepyrophosphorylase (GDP-ManPP) from Salmonella enterica and may serve as
      useful probes for mannosyltransferase activity.

PMID- 18802558
TI  - Transistors from a conjugated macrocycle molecule: field and photo effects.
AB  - This study explores a conjugated macrocycle molecule and details its synthesis,
      molecular structure, assemblies in the solid state and application in
      phototransistors.

PMID- 18802559
TI  - Nanoparticles of iron(II) spin-crossover.
AB  - We report the synthesis of spin crossover 69 nm spherical nanoparticles of
      [Fe(NH2-trz)3](Br)2.3H2O.0.03(surfactant) (NH2trz = 4-amino-1,2,4-triazole,
      surfactant = Lauropal), prepared by the reverse micelle technique, which exhibit
      at room temperature a thermal hysteresis characterized by magnetic, diffuse
      reflectivity and Raman studies.

PMID- 18802560
TI  - An electrochemical sensor for 3,4-dihydroxyphenylacetic acid with carbon
      nanotubes as electronic transducer and synthetic cyclophane as recognition
      element.
AB  - A new electrochemical sensor was demonstrated for selective sensing of 3,4
      dihydroxyphenylacetic acid (DOPAC) through a non-oxidative mechanism by using
      single-walled carbon nanotubes (SWNTs) as the electronic transducer and a
      synthetic cyclophane electron acceptor as the recognition element.

PMID- 18802561
TI  - Cyclometallated platinum(II) complexes incorporating ethynyl-flavone ligands:
      switching between triplet and singlet emission induced by selective binding of
      Pb2+ ions.
AB  - Platinum-ethynylflavone complexes featuring various polyether arms display 3IL
      phosphorescence associated with the appended flavone perturbed by the platinum
      centre (tau approximately 20 micros), but switch dramatically to flavone
      localised 1IL fluorescence (tau approximately 2 ns) upon selective binding of
      Pb2+.

PMID- 18802562
TI  - Highly stable dendritic trityl radicals as oxygen and pH probe.
AB  - Novel dendritic trityl radicals (DTR1 and DTR2) with a TAM radical core, PAMAM
      branching and carboxylate exterior surface exhibit high stability towards
      oxidoreductants as evidenced by their electrochemical and EPR properties,
      offering potential application as dual oxygen and pH probe.

PMID- 18802563
TI  - Fused tetracycles with a benzene or cyclohexadiene core: [2 + 2 + 2]
      cycloadditions on macrocyclic systems.
AB  - A series of fused tetracycles with a benzene or cyclohexadiene core (2a-h) is
      satisfactorily prepared by intramolecular [2 + 2 + 2] cycloadditions of triynic
      and enediynic macrocycles (1a-h) under RhCl(PPh3)3 catalysis; the
      enantioselective cycloaddition of macrocycles 1b and 1e and gives chiral
      tetracycles with moderate enantiomeric excess.

PMID- 18802564
TI  - Hydrogen adsorption in microporous organic framework polymer.
AB  - A microporous organic framework polymer (OFP) based on a polyimide framework
      exhibits a high surface area (1159 m2 g(-1)) and shows a reversible H2 storage
      capacity of 3.94 wt% at 10 bar and 77 K, the highest yet reported for an organic
      polymer.

PMID- 18802565
TI  - An easy entry to optically active alpha-amino phosphonic acid derivatives using
      phase-transfer catalysis (PTC).
AB  - The unprecedented use of phase-transfer catalysis (PTC) in an asymmetric
      hydrophosphonylation reaction allows the obtainment of a range of optically
      active alpha-amino phosphonic acid derivatives directly from alpha-amido
      sulfones.

PMID- 18802566
TI  - Lamellar carbon nanosheets function as templates for two-dimensional deposition
      of tubular titanate.
AB  - A novel composite composed of tubular titanate-two dimensionally deposited carbon
      nanosheets was prepared with carbon nanosheets as templates through intercalation
      and hydrothermal treatment; this nanotube-based composite and its calcined
      products exhibit both excellent adsorptivity and high photocatalytic activity
      toward organic molecules.

PMID- 18802567
TI  - Dendrimers as size selective inhibitors to protein-protein binding.
AB  - This communication describes how the "quantized" size effect of dendrimers can be
      exploited towards a size selective binding mechanism for the inhibition of
      protein-protein binding.

PMID- 18802568
TI  - Electrochemical biosensor featuring a two-enzyme pathway and DNA for screening
      toxic reactive metabolites of arylamines.
AB  - We demonstrate for the first time a biosensor featuring a sequential two-enzyme
      pathway suitable to screen potentially toxic reactive metabolites generated
      during metabolism.

PMID- 18802569
TI  - Colloidal deposition synthesis of supported gold nanocatalysts based on Au-Fe3O4
      dumbbell nanoparticles.
AB  - Highly active Au catalysts with a dumbbell-like heterostructure for CO oxidation
      were prepared through colloidal deposition method; both activities and
      stabilities were investigated under different experimental conditions.

PMID- 18802570
TI  - Enantioselective organocatalyzed Henry reaction with fluoromethyl ketones.
AB  - Remarkable generality in scope of new C9-benzoylcupreines bearing electron
      withdrawing substituents for the nitroaldol condensation with fluoromethyl
      ketones is presented. Both tri- and difluoromethyl ketones provided excellent
      levels of stereoinduction (ee 76-99%) under mild reaction conditions and low
      loading of catalyst (1-5 mol%).

PMID- 18802571
TI  - The preparation of stable aziridinium ions and their ring-openings.
AB  - The reaction of enantiomerically pure 2-substituted 1-phenylethyl-aziridine with
      methyl trifluoromethanesulfonate generated a stable methylaziridinium ion, which
      was reacted with various external nucleophiles, including nitrile, to yield
      synthetically valuable and optically pure acyclic amine derivatives in a
      completely regio- and stereoselective manner.

PMID- 18802572
TI  - Carbohydrate microarrays as powerful tools in studies of carbohydrate-mediated
      biological processes.
AB  - Carbohydrate microarrays have become very powerful tools to elucidate the
      molecular basis of carbohydrate-recognition events in a high-throughput manner.
      This microarray technology has been applied in the rapid analysis of the binding
      properties of a variety of binding partners such as lectins, antibodies,
      mammalian cells, pathogens and viruses. In this feature article, methods for the
      preparation of carbohydrate microarrays and their applications in biological and
      biomedical research are described.

PMID- 18802573
TI  - Glycoarrays--tools for determining protein-carbohydrate interactions and
      glycoenzyme specificity.
AB  - Carbohydrate arrays (glycoarrays) have recently emerged as a high-throughput tool
      for studying carbohydrate-binding proteins and carbohydrate-processing enzymes. A
      number of sophisticated array platforms that allow for qualitative and
      quantitative analysis of carbohydrate binding and modification on the array
      surface have been developed, including analysis by fluorescence spectroscopy,
      mass spectrometry and surface plasmon resonance spectroscopy. These platforms,
      together with examples of biologically-relevant applications are reviewed in this
      Feature Article.

PMID- 18802574
TI  - Oxidation induced by the antioxidant glutathione (GSH).
AB  - Remarkably efficient oxygen atom transfer from an intermediate of glutathione
      (GSH) autoxidation to an organometallic ruthenium arene thiolato complex is
      observed under physiologically-relevant conditions.

PMID- 18802575
TI  - Selectivity of mechanochemical chain scission in mixed palladium(II) and
      platinum(II) coordination polymers.
AB  - The selectivity of ultrasound induced chain scission was studied in reversible
      polymers with coordinative bonds (Pd-P and Pt-P) of different strengths in
      series.

PMID- 18802576
TI  - Microwave-assisted synthesis of near-infrared fluorescent sphingosine
      derivatives.
AB  - Microwave-assisted synthesis of near-infrared fluorescent sphingosine derivatives
      is described, and the utility of the probes demonstrated by co-localization
      studies with visible wavelength fluorescent sphingosine derivatives.

PMID- 18802577
TI  - Fine control over the morphology and structure of mesoporous silica nanomaterials
      by a dual-templating approach.
AB  - Mesoporous silica nanomaterials with varied morphologies and pore structures,
      including nanospheres, nanoellipsoids, helical nanorods and multi-lamellar
      nanovesicles, were synthesized by using cetyltrimethylammonium bromide (CTAB) and
      sodium bis(2-ethylhexyl) sulfosuccinate (AOT) as co-templates.

PMID- 18802578
TI  - QM/MM simulations predict a covalent intermediate in the hen egg white lysozyme
      reaction with its natural substrate.
AB  - Quantum mechanics/molecular mechanics (QM/MM) molecular dynamics simulations
      indicate that the reaction of native HEWL with its natural substrate involves a
      covalent intermediate, in contrast to the 'textbook' mechanism for this seminal
      enzyme.

PMID- 18802579
TI  - Hydroxylamine as an oxygen nucleophile. Chemical evidence from its reaction with
      a phosphate triester.
AB  - The reaction of hydroxylamine with 2,4-dinitrophenyl diethyl phosphate gives the
      O-phosphorylated product, which is rapidly converted to hydrazine and nitrogen
      gas in the presence of the excess of hydroxylamine.

PMID- 18802580
TI  - Biocompatible bacteria@Au composites for application in the photothermal
      destruction of cancer cells.
AB  - We have successfully transformed the infectious E. coli bacteria into
      biocompatible bacteria@Au composites for photothermal therapy.

PMID- 18802581
TI  - Selective synthesis of double temperature-sensitive polymer-peptide conjugates.
AB  - A novel synthetic route has been developed to couple selectively a modified octa
      peptide, that is able to gel at low temperature, to the prototypical
      thermoresponsive polymer poly(N-isopropylacrylamide) to give a bioconjugate that
      exhibits double thermoresponsiveness.

PMID- 18802582
TI  - Kagome type extra-large microporous solid based on a paddle-wheel Cu2+ dimer.
AB  - A robust extra-large microporous coordination polymer with a Kagome type
      structure was synthesized by carboxylate/amine multifunctional ligand with a Cu2+
      cluster and the hexagonal 1D channels (approximately 15 A) showed type I and IV
      adsorption isotherms for gas molecules.

PMID- 18802583
TI  - Energetics of conformational conversion between 1,1,2-trichloroethane polymorphs.
AB  - Pressure-induced transformations between gauche-, gauche+ and transoid
      conformations have been evidenced by X-ray single-crystal diffraction for 1,1,2
      trichloroethane, and the energies of intermolecular interactions, conformational
      conversion, and the latent heat have been determined.

PMID- 18802584
TI  - Amphiphilic block copolymer-stabilized gold nanoparticles for aerobic oxidation
      of alcohols in aqueous solution.
AB  - Stable Au nanoparticles in P123 aqueous solution using a simple method have been
      developed and the colloidal Au nanoparticles were successfully applied for the
      effective oxidation of various alcohols using molecular O2 as oxidant at 30
      degrees C in aqueous solution.

PMID- 18802585
TI  - Unusual temperature dependence of salt effects for "on water" Wittig reaction:
      hydrophobicity at the interface.
AB  - An unusual variation with temperature of the salt effects in aqueous Wittig
      reaction is observed, suggesting that hydrophobic acceleration of reactions
      comprising "on water" reactants is fundamentally different from that for
      reactions with small non-polar solutes.

PMID- 18802586
TI  - Temporal and spatial imaging of hydrogen storage materials: watching solvent and
      hydrogen desorption from aluminium hydride by transmission electron microscopy.
AB  - An in situ thermal desorption study of solvated aluminum hydride (alane) by
      transmission electron microscopy and selected area diffraction has permitted
      characterisation of the structural and morphological changes during desorption of
      solvent and hydrogen in real-time; this powerful technique for studying hydrogen
      storage materials complements several others already employed.

PMID- 18802587
TI  - Enhancement of the electrocatalytic activity of gold nanoparticles via NaBH4
      treatment.
AB  - We report on the enhancement of the electrocatalytic activity of Au nanoparticles
      after NaBH4 treatment and its application to H2O2 detection.

PMID- 18802588
TI  - Enhanced long-wavelength transient photoresponsiveness of WO3 induced by
      tellurium doping.
AB  - Tungsten trioxide (WO3) films doped with 0.25 atom% tellurium synthesised by a
      sol-gel route, show strong transient photocurrents under chopped sub-bandgap
      illumination (hnu=1.8 eV<Eg) at low bias potentials from 0.2 to 0.7 V; such
      effects are ascribed to the presence of a localized narrow band (NB) between the
      VB and the CB in this material.

PMID- 18802589
TI  - Homogeneous photochemical oxidation via singlet O2 in supercritical CO2.
AB  - This communication describes the reaction chemistry of singlet oxygen in
      supercritical carbon dioxide, demonstrating rapid and quantitative conversion of
      alpha-terpinene to ascaridole.

PMID- 18802590
TI  - Cyanide-bridged tetradecanuclear RuII3MII11 clusters (MII=ZnII and CuII) based on
      the high connectivity building block [Ru3(HAT)(CN)12]6-: structural and
      photophysical properties.
AB  - Reaction of the anionic cyanometallate chromophore [{Ru(CN)4}3(micro3-HAT)]6-
      with [MII(tren)]2+ complexes (M=ZnII, CuII) provides discrete tetradecanuclear
      clusters of formula [{MII(tren)(micro-CN)}11{Ru3(HAT)(CN)}]16+; the weak
      luminescence of the Ru3 chromophore is substantially enhanced in the presence of
      ZnII ions, whereas it is completely quenched when CuII centers are present.

PMID- 18802591
TI  - A facile approach to fabricate functionalized superparamagnetic copolymer-silica
      nanocomposite spheres.
AB  - Novel amino- or thiol-functionalized superparamagnetic copolymer-silica
      nanospheres (NH2-SMCSNs/SH-SMCSNs), which consist of a magnetic core and a silica
      cross-linked block copolymer shell, have been fabricated.

PMID- 18802592
TI  - Cyanurate-guided self-assembly of a melamine-capped oligo(p-phenylenevinylene).
AB  - An oligo(p-phenylenevinylene) capped on one end by a monotopic DAD-type triple
      hydrogen-bonding module shows distinct optical properties as well as self
      organization behavior upon complexation with cyanurates with different numbers of
      ADA-type triple hydrogen-bonding sites.

PMID- 18802594
TI  - PVP-functionalized nanometre scale metal oxide coatings for cathode materials:
      successful application to LiMn2O4 spinel nanoparticles.
AB  - PVP functionalized metal oxide coatings on spinel nanoparticles demonstrated
      significantly improved rate characteristics under extensive cycling at 65 degrees
      C and exhibited over 100% improved capacity retention compared to the bare
      counterpart.

PMID- 18802593
TI  - The convenient fluorescence turn-on detection of heparin with a silole derivative
      featuring an ammonium group.
AB  - A new silole derivative with an ammonium group was designed and studied with a
      view to developing a convenient fluorescence turn-on assay for heparin by taking
      advantage of the aggregation-induced enhanced emission (AIE) feature of silole
      (silacyclopentadiene) molecules.

PMID- 18802595
TI  - Ultra stable ordered mesoporous phenol/formaldehyde polymers as a heterogeneous
      support for vanadium oxide.
AB  - Ordered mesoporous phenol/formaldehyde polymers are presented as an ultra stable
      heterogeneous support for vanadium oxide.

PMID- 18802596
TI  - Hierarchical carbon nanotube assemblies created by sugar-boric or boronic acid
      interactions.
AB  - We previously found that polysaccharide "schizophyllan (SPG)" can entrap as-grown
      and cut single-walled carbon nanotubes (as-SWNTs and c-SWNTs, respectively): we
      here reported that the c-SWNT-s-SPG (single stranded SPG) composites thus
      obtained can be aligned regularly using the covalent bond formation between boric
      acid or boronic acid derivatives and the 4,6-dihydroxyl group of the glucose side
      chain unit.

PMID- 18802597
TI  - Open cellular reactive porous membranes from high internal phase emulsions.
AB  - High internal phase emulsions (HIPEs) incorporating styrene, 4-vinylbenzyl
      chloride, divinylbenzene and ethylhexyl acrylate were applied to prepare
      reactive, cross-linked porous membranes with open cellular architecture and
      thicknesses between 30 and 500 microm.

PMID- 18802598
TI  - Electrochemical oxidation of double-stranded polybisnorbornenes containing
      linearly aligned ferrocene linkers.
AB  - Seventy percent of the ferrocene moieties in double-stranded polybisnorbornenes
      containing linearly aligned ferrocene linkers are oxidised and each of the
      neighbouring monomeric units in these polymers may strongly interact with each
      other; the oxidised form of has been shown to be antiferromagnetic.

PMID- 18802599
TI  - Direct functionalization at the boron center of antiaromatic chloroborole.
AB  - The presence of a reactive B-Cl bond allowed for the direct functionalization of
      the boron center in antiaromatic chloroborole ClBC4Ph4, thus allowing for a
      selective fine tuning of the optical properties of borole derivatives and
      facilitating a potential new approach toward the introduction of borole moieties
      into the backbone of organic pi-conjugated frameworks.

PMID- 18802600
TI  - BiPh3--a convenient synthon for heavy alkaline-earth metal amides.
AB  - Environmentally friendly, commercially available BiPh3 reacts with heavy alkaline
      earth metals (Ae) and bulky trimethylsilylamines to give the corresponding amides
      [Ae{N(SiMe3)(R)}2(thf)n] (R=SiMe3, 2,4,6-Me3C6H2, 2,6-iPr2C6H3) in good yields,
      providing proof of concept for a general synthetic method.

PMID- 18802601
TI  - Selective mono reduction of bis-phosphine oxides under mild conditions.
AB  - Bis-phosphine oxides can be selectively reduced to bis-phosphine monoxides under
      exceptionally mild conditions using triflic anhydride and a thiol.

PMID- 18802602
TI  - A self-propagating system for Ge incorporation into nanostructured silica.
AB  - Technologically-relevant levels of Ge can be incorporated into cell wall silica
      of the diatom Thalassiosira pseudonana with no aberration in structure at low
      levels, whereas higher levels alter structure.

PMID- 18802603
TI  - Oxidative decarboxylative synthesis of 2-H-imidazolines from glyoxylic acid and
      1,2-diamines.
AB  - A novel method to prepare 2-H-imidazolines from glyoxylic acid monohydrate and
      1,2-diamines is described; the key reaction of this method is the oxidative
      decarboxylation of the 2-carboxy imidazolidines by NBS.

PMID- 18802604
TI  - Microwave effect on the surface composition of the Urushibara Ni hydrogenation
      catalyst and improved reduction of acetophenone.
AB  - The Urushibara Ni (U-Ni) hydrogenation catalyst and some modified forms, and for
      comparison Raney-Ni, were subjected to conventional (oil bath) and MW heating,
      and subsequently characterized by electron dispersive X-ray analysis (EDX), by
      BET surface area, and by scanning electron microscopy (SEM); yields of the
      catalyzed hydrogenation of acetophenone to 1-phenylethanol in 2-propanol by one
      of the modified forms (U-Ni-B) were greatly improved (from 68% to 95%).

PMID- 18802605
TI  - Improved oxygen mobility in nanosized mixed-oxide particles synthesized using a
      simple nanocasting route.
AB  - This work reports the synthesis of homogeneously dispersed mixed-oxide
      nanoparticles (<5 nm) exhibiting improved lattice oxygen mobility (ca. two times
      higher than on bulk samples), using a novel synthesis procedure of nanocasting in
      mesoporous silica host support.

PMID- 18802606
TI  - Nitrogen-15 NMR spectroscopy of N-metallated nucleic acids: insights into 15N NMR
      parameters and N-metal bonds.
AB  - It was recently demonstrated spectroscopically that RNA/DNA nucleobases can bind
      to metal cations in aqueous solution through coordination bonds and covalent
      bonds. Nitrogen-15 (15N) NMR spectroscopy was employed and shown to be a powerful
      tool for determining the mode of metal ion binding to nitrogen atoms in RNA/DNA
      molecules. This review describes 15N NMR spectroscopic characteristics in
      accordance with the mode of metal ion binding to nitrogen atoms. The general
      rules for 15N chemical shift changes, which are applicable to the determination
      of the metal ion binding mode of N-metallated compounds, are also described.

PMID- 18802607
TI  - Isolation and characterisation of a (-)-sparteine coordinated mixed alkyl/amido
      sodium magnesiate, a chiral variant of an important utility ate base.
AB  - When a 1:1 nBuNa-n,sBu2Mg mixture is treated with two molar equivalents of TMP(H)
      (TMP=2,2,6,6-tetramethylpiperidide) and one molar equivalent of (-)-sparteine in
      hydrocarbon medium, a new chiral mixed-metal, mixed alkyl-amide [{(-)
      sparteine}.Na(micro-Bu)(micro-TMP)Mg(TMP)] can be isolated.

PMID- 18802608
TI  - The unusual binding abilities of the His-analogue of Arg-vasopressin towards
      Cu2+.
AB  - A new vasopressin analogue, [His1,6]AVP, was synthesized and characterized by
      potentiometric measurements as well as by UV-Vis, CD and EPR spectroscopy. At the
      physiological pH the peptide forms a stable complex with Cu2+ ions which is
      characterized by the {NH2, NIm, NIm(macrochelate)} binding mode. The replacement
      of both Cys by His residues in the vasopressin sequence results in a very
      significant increase in the efficiency of Cu2+ binding.

PMID- 18802609
TI  - Four- and five-membered cobaltacycles by regioselective cyclometallation of
      benzyl sulfide derivatives via Co(v) intermediates.
AB  - C-H activation through the coordination of a benzyl sulfide anchoring group with
      a C-S bond cleavage at a Co(v) center constitutes a regiospecific access to four-
      and five-membered metallacycles under mild conditions.

PMID- 18802611
TI  - Stereochemical nomenclature for octahedral coordination compounds containing
      polydentate ligands: a comprehensive proposal.
AB  - A universal nomenclature for the stereoisomers of octahedral coordination
      compounds containing polydentate ligands is hitherto lacking. A proposal for
      naming such compounds in a systematic and unequivocal way is described. Two skew
      chelate rings are selected following simple rules, and their helicity is assigned
      to the complex. Thence, a single descriptor is obtained and the exhaustive
      examination of all the possible pairs of lines is avoided. Another proposal,
      closer to the current notation, is reported and the advantages and disadvantages
      of both are discussed.

PMID- 18802610
TI  - The donor ability of the chelated carbonate ligand: protonation and metallation
      of [(L)Co(O2CO)]+ complexes in aqueous solution.
AB  - The syntheses and X-ray structures of [Co(Me-tpa)O2COZnCl3],
      [Co(pmea)O2COZnCl3].H2O [Co(trpyn)O2COZn(OH2)4OCO2Co(trpyn)](ZnCl4)2.H2O,
      [Co(trpyn)(O2COH)]ZnCl(4).3H2O and [Co(trpyn)(O2CO)]ClO4 are reported (Me-tpa=[(6
      methyl-2-pyridyl)methyl]bis(2-pyridylmethyl)amine, pmea=bis(2-pyridylmethyl)-2-(2
      pyridylethyl)amine, trpyn=tris(2-(1-pyrazolyl)ethyl)amine). The chelated
      bicarbonate complex [Co(trpyn)(O2COH)]ZnCl(4).3H2O is isolated as a crystalline
      solid from an acidic solution of the parent carbonate [Co(trpyn)(O2CO)]ClO4, and
      X-ray structural analysis shows that lengthening of the C=Oexo bond and
      shortening of the C-Oendo bond accompanies protonation. The bimetallic complex
      [Co(Me-tpa)O2COZnCl3] results from the unexpected coordination of ZnCl3- to the
      exo O atom of a chelated carbonate ligand. This complex is obtained from both
      acidic and neutral solutions in which [Zn2+]=1.0 M, while the structurally
      similar complex [Co(pmea)O2COZnCl3].H2O is isolated from an analogous neutral
      solution. The trimetallic complex
      [Co(trpyn)O2COZn(OH2)4OCO2Co(trpyn)](ZnCl4)2.H2O crystallises on prolonged
      standing of [Co(trpyn)(O2CO)]ClO4 in a neutral solution having [Zn2+]=1.0 M. The
      Zn-O bond lengths in all three complexes are indicative of bonds of significant
      strength. DFT calculations show that the nature of the bonding interaction
      between the Co(III) ion and the endo O atoms of the carbonate ligand remain
      essentially unaffected by coordination of Zn2+ to the exo O atom. They also show
      that such coordination of Zn2+ decreases the C-Oexo bond order.

PMID- 18802612
TI  - Syntheses, crystal and molecular structures, and properties of some new
      phenylmercury(II) dithiolate complexes.
AB  - A series of new phenylmercury(II) dithio complexes [PhHg(Bun2dtc)] (; Bun2dtc-=di
      n-butyldithiocarbamate), [PhHg(morphdtc)] (; morphdtc
      =morpholinedithiocarbamate), [PhHg(Bz2dtc)] (; Bz2dtc-=dibenzyldithiocarbamate),
      [PhHg(methoxethxant)] (; methoxethxant-=2-methoxyethylxanthate) [(PhHg)2NED] (;
      NED2-=1-nitroethylene-2,2-dithiolate) and [(PhHg)2CDC] (; CDC2
      =cyanodithioimidocarbonate) have been prepared and characterized by elemental
      analysis, UV-Vis, IR, 1H and 13C NMR spectra and mass spectrometry. The crystal
      structures of , and showed a linear Hg(II) core at the center of the molecules.
      The weak intra- and intermolecular HgS interactions provide a molecular chain
      framework. The reaction of PhHgO2CCH3 with Bun2dtcH gave the known dimeric
      complex Hg(Bun2dtc)2 while the Ni(O2CCH3)2 mediated reaction gave instead of the
      expected heterobimetallic complex [PhHgNi(Bun2CS2)2]O2CCH3 which has been
      corroborated by natural charges at each atom obtained at the density functional
      level (DFT) of theory. Upon excitation at 358 nm exhibited a medium strong
      photoluminescence emission at 420 nm as a consequence of intraligand pi-->pi*
      transitions. The electronic absorption bands of were assigned from time dependent
      density functional theory (TD-DFT) calculations. Geometrical configurations of ,
      and have been optimized using the DFT method. All of the complexes are weakly
      conducting (sigmart approximately 10(-12) S cm(-1)). However and exhibited
      semiconductivity with band gaps of 0.39 and 0.94 eV respectively.

PMID- 18802613
TI  - Copper diphosphonates with zero-, one- and two-dimensional structures:
      ferrimagnetism in layer compound Cu3(ImhedpH)(2).2H2O [ImhedpH4=(1
      C3H3N2)CH2C(OH)(PO3H2)2].
AB  - Reactions of CuSO4 with 2-(1-imidazole)-1-hydroxy-1,1'-ethylidenediphosphonic
      acid (ImhedpH4) under hydrothermal conditions at different temperatures lead to
      four new metal phosphonates: Cu(ImhedpH3)2(H2O).2H2O (), Cu(ImhedpH3)2 (),
      Cu3(ImhedpH2)2(ImhedpH3)(2).4H2O (), and Cu3(ImhedpH)(2).2H2O (). Compounds and
      have mononuclear structures in which the Cu atoms adopt square pyramidal and
      square planar geometries, respectively. In compound , a chain structure is
      observed where the Cu3(ImhedpH2)2(ImhedpH3)2 trimer units are connected by edge
      sharing of the {Cu2O5} square pyramids. Compound exhibits a layer structure made
      up of Cu3(ImhedpH)2 trimer units. The connection of trimers through corner
      sharing of {Cu1O4} and {CPO3} tetrahedra results in a two-dimensional layer
      containing 8- and 16-membered rings. The imidazole groups are grafted on the two
      sides of the layer. Magnetic studies reveal that ferromagnetic interactions are
      mediated in , while for compound , ferrimagnetism is observed below 5.8 K.

PMID- 18802614
TI  - Synthesis, characterization and reactivity of heteroleptic rare earth metal
      bis(phenolate) complexes.
AB  - The synthesis, characterization and reactivity of heteroleptic rare earth metal
      complexes supported by the carbon-bridged bis(phenolate) ligand 2,2'-methylene
      bis(6-tert-butyl-4-methyl-phenoxo) (MBMP2-) are described. Reaction of
      (C5H5)3Ln(THF) with MBMPH2 in a 1:1.5 molar ratio in THF at 50 degrees C produced
      the heteroleptic rare earth metal bis(phenolate) complexes (C5H5)Ln(MBMP)(THF)n
      (Ln=La, n=3 (); Ln=Yb (), Y (), n=2) in nearly quantitative yields. The residual
      C5H5- groups in complexes to can be substituted by the bridged bis(phenolate)
      ligands at elevated temperature to give the neutral rare earth metal
      bis(phenolate) complexes, and the ionic radii have a profound effect on the
      structures of the final products. Complex reacted with MBMPH2 in a 1:0.5 molar
      ratio in toluene at 80 degrees C to produce a dinuclear complex
      (MBMP)La(THF)(micro-MBMP)2La(THF)2 () in good isolated yield; whereas complexes
      and reacted with MBMPH2 under the same conditions to give (MBMP)Ln(MBMPH)(THF)2
      (Ln=Yb (), Y ()) as the final products, in which one hydroxyl group of the phenol
      is coordinated to the rare earth metal in a neutral fashion. The reactivity of
      complexes and with some metal alkyls was explored. Reaction of complex with 1
      equiv. of AlEt3 in toluene at room temperature afforded unexpected ligand
      redistributed products, and a discrete ion pair ytterbium complex
      [(MBMP)Yb(THF)2(DME)][(MBMP)2Yb(THF)2] () was isolated in moderate yield.
      Furthermore, reaction of complex with 1 equiv. of ZnEt2 in toluene gave a ligand
      redistributed complex [(micro-MBMP)Zn(THF)]2 () in reasonable isolated yield.
      Similar reaction of complex with ZnEt2 also afforded complex ; whereas the
      reaction of complex with 1 equiv. of n-BuLi in THF afforded the heterodimetallic
      complex [(THF)Yb(MBMP)2Li(THF)2] (). All of these complexes were well
      characterized by elemental analyses, IR spectra, and single-crystal structure
      determination, in the cases of complexes , and -.

PMID- 18802615
TI  - Nitrosation of N-methylhydroxylamine by nitroprusside. A kinetic and mechanistic
      study.
AB  - The kinetics of the reaction between aqueous solutions of Na2[Fe(CN)5NO].2H2O
      (sodium pentacyanonitrosylferrate(II), nitroprusside, SNP) and MeN(H)OH (N
      methylhydroxylamine, MeHA) has been studied by means of UV-vis spectroscopy,
      using complementary solution techniques: FTIR/ATR, EPR, mass spectrometry and
      isotopic labeling (15NO), in the pH range 7.1-9.3, I=1 M (NaCl). The main
      products were N-methyl-N-nitrosohydroxylamine (MeN(NO)OH) and [Fe(CN)5H2O]3-,
      characterized as the [Fe(CN)5(pyCONH2)]3- complex (pyCONH2=isonicotinamide). No
      reaction occurred with Me2NOH (N,N-dimethylhydroxylamine, Me2HA) as nucleophile.
      The rate law was: R=kexp [Fe(CN)5NO2-]x[MeN(H)OH]x[OH-], with kexp=1.6+/
      0.2x10(5) M(-2) s(-1), at 25.0 degrees C, and DeltaH#=34+/-3 kJ mol(-1), DeltaS#=
      32+/-11 J K(-1) mol(-1), at pH 8.0. The proposed mechanism involves the formation
      of a precursor associative complex between SNP and MeHA, followed by an OH-
      assisted reversible formation of a deprotonated adduct, [Fe(CN)5(N(O)NMeOH)]3-,
      and rapid dissociation of MeN(NO)OH. In excess SNP, the precursor complex reacts
      through a competitive one-electron-transfer path, forming the [Fe(CN)5NO]3- ion
      with slow production of small quantities of N2O. The stoichiometry and mechanism
      of the main adduct-formation path are similar to those previously reported for
      hydroxylamine (HA) and related nucleophiles. The nitrosated product, MeN(NO)OH,
      decomposes thermally at physiological temperatures, slowly yielding NO.

PMID- 18802616
TI  - X-Ray crystal structures of five-coordinate (salen)MnN3 derivatives and their
      binding abilities towards epoxides: chemistry relevant to the epoxide-CO2
      copolymerization process.
AB  - The synthesis of several (salen)MnN3 complexes in good yields and purities were
      achieved by the reaction of manganese(III) acetate and H2salen, followed by
      metathesis of the remaining acetate ligand with an aqueous solution of NaN3. The
      X-ray structures of two derivatives, where salen=N,N'-bis(3,5-di-tert
      butylsalicylidene)-1,2-ethylenediamine and N,N'-bis(3,5-di-tert
      butylsalicylidene)-1,2-cyclohexenediamine respectively, were determined. The
      complexes were shown to be monomeric 5-coordinate derivatives displaying a
      distorted square pyramidal geometry, and to be d4 high-spin derivatives by
      solution magnetic moment measurements using the Evans method. Binding studies of
      the (salen)MnN3 derivatives with added azide ions or cyclohexene oxide showed
      these complexes to have modest affinities for binding a sixth ligand. These
      observations are used to rationalize the low activity exhibited by manganese(III)
      complexes relative to their chromium(III) and cobalt(III) analogs for serving as
      catalysts for the copolymerization of carbon dioxide and epoxides.

PMID- 18802617
TI  - A neutral molecular-based layered magnet [Fe(C2O4)(CH3OH)]n exhibiting magnetic
      ordering at TN approximately 23 K.
AB  - Solvothermal synthesis of FeCl(2).4H2O and H2C2O(4).2H2O in methanol at 120
      degrees C yielded yellow plate-like crystals of [Fe(C2O4)(CH3OH)]n. Each iron
      atom is in a distorted octahedral environment, being bonded to four oxygen atoms
      from two bisbidentate oxalate anions, one O atom of a chelating oxalate anion and
      one O atom from a methanol molecule as an oxalate group bridging ligand in a five
      coordination mode. The neutral layer of [Fe(C2O4)(CH3OH)]n with a [4,4] net along
      the ac plane. There is no interaction between layers. A long range magnetic
      ordering with spin canting at TN approximately 23 K was observed and confirmed by
      AC susceptibility measurements.

PMID- 18802618
TI  - More user-friendly phosphines? Molecular structure of methylphosphine and its
      adduct with borane, studied by gas-phase electron diffraction and quantum
      chemical calculations.
AB  - The molecular structures of methylphosphine (CH3PH2) and methylphosphine-borane
      (CH3PH2.BH3) have been determined from gas-phase electron diffraction data and
      rotational constants, employing the SARACEN method. The experimental geometric
      parameters generally showed a good agreement with those obtained using ab initio
      calculations and previous microwave spectroscopy studies. In order to assess the
      accuracy of the calculated structures a range of ab initio methods were used,
      including the CCSD(T) method, with correlation-consistent basis sets. The
      structural environment around the phosphorus atom was found to change
      significantly upon complexation with borane, with the P-C bond length shortening
      and the bond angles widening.

PMID- 18802619
TI  - New reagents for the synthesis of a series of ferrocenoyl functionalized copper
      and silver chalcogenolate complexes.
AB  - A series of silylated ferrocenoyl chalcogenide reagents, FcC(O)ESiMe3 (E=S, Se,
      Te; Fc=ferrocene), can be prepared in very good yield from FcC(O)Cl and LiESiMe3.
      These reagents are used in the preparation of triphenylphosphine-ligated copper
      and silver ferrocenoyl thiolate and selenolate complexes, [M4(E{O}CFc)4(PPh3)4],
      (M=Cu, Ag; E=S, Se) and [Cu2(micro-Se{O}CFc)2(PPh3)3] from solubilized copper(I)
      and silver(I) acetate. The structures of these complexes have been determined via
      single-crystal X-ray diffraction. The driving force for these reactions is the
      thermodynamically favorable formation and elimination of AcOSiMe3. The synthesis
      and characterization of both starting reagents and cluster complexes are
      discussed.

PMID- 18802620
TI  - Selective halogenation at the pnictogen atom in Lewis-acid/base-stabilised
      phosphanylboranes and arsanylboranes.
AB  - The halogenation of Lewis-acid/base-stabilised phosphanylboranes () and
      arsanylboranes () with CX4 (X=Cl, Br) leads selectively to the substitution of
      both protons at the pentel atom and the new compounds [(CO)5W(X2PBH2.NMe3)]
      (:X=Cl, :X=Br) and [(CO)5W(X2AsBH2.NMe3)] (:X=Cl, :X=Br), respectively, are
      obtained. The new products were comprehensively characterised by spectroscopic
      methods and by X-ray crystallography. While compounds and show an antiperiplanar
      arrangement of the Lewis acid (W(CO)5) and the Lewis base (NMe3) in the solid
      state, a synclinal arrangement in and , respectively, was observed. Computational
      calculations of the optimised antiperiplanar and synclinal geometries of the
      compounds and in the gas phase slightly favour the antiperiplanar arrangement of
      the Lewis acid and the Lewis base for both compounds.

PMID- 18802621
TI  - Complex formation processes of terminally protected peptides containing two or
      three histidyl residues. Characterization of the mixed metal complexes of
      peptides.
AB  - Copper(II), nickel(II) and zinc(II) complexes of the peptides Ac-HVVH-NH2 and Ac
      HAAHVVH-NH2 have been studied by potentiometric, UV-vis, CD, EPR and NMR
      spectroscopic measurements. Both tetra and heptapeptides can form relatively
      stable macrochelates with copper(II), nickel(II) and zinc(II) ions, in which the
      ligands are coordinated via the side-chain imidazole functions. Formation of the
      macrochelates slightly suppresses, but cannot prevent the copper(II) and
      nickel(II) ion promoted deprotonation and coordination of the amide
      functionalities. The overall stoichiometry of the major species is [MH(-3)L]-
      with a 4N (=N-,N-,N-,Nim) coordination mode. In the case of Ac-HAAHVVH-NH2,
      coordination isomers of this species can exist with a preference for copper(II)
      or nickel(II) binding at the internal histidyl residue. In the copper(II)-Ac
      HAAHVVH-NH2 system, the presence of the two anchoring sites results in the
      formation of dinuclear complexes. The existence of these species requires the
      involvement of amide functions in metal binding. Both equilibrium and
      spectroscopic data support the fact that the copper(II) ions of the dinuclear
      species are independent from each other providing a good chance for the formation
      of various mixed metal complexes. It was found that zinc(II) is not able to
      significantly alter the copper(II) binding of the heptapeptide, but it can occupy
      the uncoordinated histidyl sites. The formation of the copper(II)-nickel(II)
      mixed species was obtained in alkaline solutions and CD spectra suggest the
      statistical distribution of the two metal ions among the histidyl residues. The
      binding of HAAHVVH to palladium(II) is exclusive below pH 8 and the mixed metal
      species of palladium(II) and copper(II) ions are formed only in slightly basic
      solutions.

PMID- 18802622
TI  - Synthesis of polyhedral phenylsilsesquioxanes with KF as the source of the
      fluoride ion.
AB  - An alternative method for the preparation of polyhedral phenylsilsesquioxanes is
      reported. Phenylsilsesquioxane resin and freshly hydrolysed
      phenyltrimethoxysilane was refluxed with various phase-transfer catalysts and
      potassium fluoride in toluene yielding octaphenylsilsesquioxane, or in a mixture
      of THF and ethanol yielding dodecaphenylsilsesquioxane.

PMID- 18802623
TI  - Sulfimidation of thioether groups--a versatile method for modifying and linking
      thia/oxa crowns.
AB  - Reaction of the mixed thioether/ether crowns [9]aneO2S , [12]aneO3S and
      [18]aneO4S2 with one mol. equivalent of the aminating agent MSH (o
      mesitylsulfonylhydroxylamine) in Et2O results in the formation of the mono
      sulfimidated systems {[9]aneO2(S=NH2)}+, {[12]aneO3(S=NH2)}+ and
      {[18]aneO4S(S=NH2)}+, while using two mol. equivalents of MSH with gives the
      disulfimidium cation {[18]aneO4(S=NH2)2}2+. All of these species have been
      isolated in good yields as the [mesSO3]- (mes=2,4,6-Me3C6H2) salts and can be
      readily converted to the [BPh4]- salts by metathesis with Na[BPh4]. Treatment of
      or with lithium diisopropylamide (LDA) and N-bromosuccinimide (NBS) at -78
      degrees C, followed by addition of a further equivalent of the parent thia/oxa
      crown, gives monocationic N-bridged sulfimide bicyclic compounds ( and
      respectively), in which the crowns are linked by the sulfimidic nitrogen.
      Reaction of with LDA and NBS leads to formation of the {([18]aneO4S2)N}+ cation
      which exhibits an intramolecular S-N-S bridge. Crystallographic studies on
      representative examples of each compound type are described, together with their
      spectroscopic properties.

PMID- 18802624
TI  - Extraction behavior of lanthanides using a diglycolamide derivative TODGA in
      ionic liquids.
AB  - Liquid-liquid extraction of lanthanides from aqueous solutions into ionic liquids
      (ILs) has been investigated using N,N,N',N'-tetra(n-octyl)diglycolamide (TODGA)
      as an extractant, and compared with that in the isooctane system. Application of
      ILs as the extracting phase provided unprecedented enhancement of the extraction
      performance of TODGA for lanthanides compared with that of the isooctane system.
      Slope analysis confirmed that TODGA in ILs formed a 1:3 complex with La3+, Eu3+,
      or Lu3+. On the other hand, the molar ratios of species extracted into isooctane
      were 1:3 for La3+ or 1:4 for Eu3+ and Lu3+, depending on the atomic number of the
      lanthanide. The transfer of lanthanides with TODGA into ILs proceeded via a
      cation-exchange mechanism, in contrast to ion pair extraction in the isooctane
      system. Furthermore, we clarified that TODGA provided selectivity for the middle
      lanthanides in the ILs systems, but heavier lanthanides in the isooctane system.

PMID- 18802625
TI  - Transition metal induced derivatisations resulting in novel coordination
      behaviour of bis(oxamato) ligands.
AB  - Two mononuclear bis(oxamato) complexes with the formula [nBu4N]2[M(2,3-acbo)]
      (M=Ni (), Cu (), with acbo=anthra-9,10-chinone-2,3-bis(oxamato) have been
      synthesized starting from symmetric diethyl N,N'-anthra-9,10-chinone-2,3
      bis(oxamate) (, 2,3-acboH2Et2). The crystal structures of and have been
      determined, verifying that the transition metal ions are eta4(kappa2N,kappa2O)
      coordinated by the [2,3-acbo]4- ligands. Using the asymmetric diethyl N,N'-anthra
      9,10-chinone-1,2-bis(oxamate) (, 1,2-acboH2Et2) leads, under otherwise identical
      reaction conditions, to the novel bis(oxamato) complex [(n)Bu4N]2[Ni(1,2-acbo)]
      () whereby in the case of Cu(II) the derivate [nBu4N]2[Cu(aibo)2] ()
      (aibo=anthra[1,2-d]-(imidazole-2-carboxylato)-6,11-dione) has been obtained. The
      crystal structures of and have been determined, displaying that the Ni(II) ion of
      is eta4(kappa2N,kappa2O) coordinated by the [1,2-acbo]4- ligand. The Cu(II) ion
      of is coordinated by two [aibo]2- ligands, giving rise to an approximately square
      planar trans-bis(aibo-N,O) arrangement. Using the symmetric diethyl N,N'-4,5
      dinitro-o-phenylene-bis(oxamate) (, niboH2Et2), possessing strongly electron
      withdrawing NO2-groups, leads under otherwise identical reaction conditions to
      the bis(oxamato) complex [nBu4N]2[Ni(nibo)] (), whereby in the case of Cu(II) the
      derivate [nBu4N]2[Cu(niqo)2] () (niqo=7,8-dinitro-2,3-quinoxalinedionato) has
      been obtained. The crystal structures of and have been determined, ensuring that
      the Ni(II) ion of is eta(4)(kappa2N,kappa2O) coordinated by the [nibo]4- ligand.
      The Cu(II) ion of is coordinated by four oxygen atoms of two [niqo]2- ligands,
      giving rise to an approximately square-planar coordination geometry.

PMID- 18802626
TI  - Bronsted-acid and Bronsted-base catalyzed Diels-Alder reactions.
AB  - The enantioselective Diels-Alder reaction is one of the most important reactions
      for the synthesis of complex molecules. It provides access to chiral six-membered
      carbocyclic compounds containing up to four stereogenic centers in a single step.
      Asymmetric catalysis in the Diels-Alder reaction has mainly been realized using
      chiral Lewis acids. In this perspective, we describe several cases of chiral
      Bronsted-acid and Bronsted-base catalyzed Diels-Alder reactions, providing an
      overview of this rapidly growing field.

PMID- 18802627
TI  - Regio- and chemoselective magnesiation of protected uracils and thiouracils using
      TMPMgCl x LiCl and TMP(2)Mg x 2 LiCl.
AB  - Two successive regio- and chemoselective magnesiations using TMPMgCl x LiCl and
      TMP(2)Mg x 2 LiCl enable the full functionalization of protected uracils and
      thiouracils in good to excellent yields.

PMID- 18802628
TI  - Synthesis of (2S)-2-amino-7,8-epoxyoctanoic acid and structure of its metal
      bridging complex with human arginase I.
AB  - The synthesis of (2S)-2-amino-7,8-epoxyoctanoic acid is reported along with the X
      ray crystal structure of its complex with human arginase I, revealing unique
      coordination interactions with two manganese ions in the enzyme active site.

PMID- 18802629
TI  - Cyclic tetraureas with variable flexibility--synthesis, crystal structures and
      properties.
AB  - Macrocyclic molecules containing several amide or urea functions may serve as
      anion receptors. We describe the synthesis of 32-membered macrocycles, in which
      four rigid xanthene units (X) and/or diphenyl ether units (D) as flexible
      analogues are linked via urea groups. All six possible combinations of these
      units (XXXX, XXXD, XXDD, XDXD, XDDD and DDDD) were synthesized and two examples
      were characterised by single-crystal X-ray analyses (DDDD and two structures for
      XXXD). Both macrocycles showed distinct differences in their overall conformation
      and consequently in their hydrogen-bonding pattern. Hydrogen-bonded solvent
      molecules are found for both compounds and intramolecular hydrogen bonds for the
      two structures of XXXD, but surprisingly no direct intermolecular hydrogen bonds
      between the macrocyclic tetraurea molecules. The interaction with various anions
      was studied by (1)H NMR spectroscopy. Stability constants for all tetramers were
      determined by UV spectroscopy for complexes with chloride, bromide, acetate and
      dihydrogenphosphate in acetonitrile-THF (3:1). The strongest binding was found
      for XXXD and acetate (log beta = 7.4 +/- 0.2), the weakest for XXXX and acetate
      (log beta = 5.1 +/- 0.5). MD simulations in chloroform and acetonitrile boxes
      show that all molecules except DDDD adopt very similar conformations
      characterized by an up-down-up-down arrangement of the spacer groups. Clustered
      solvation shells of acetonitrile molecules around XXXX and DDDD suggest their
      preorganization for spherical/planar and tetrahedral/bidentate anions,
      respectively, which in turn was corroborated by simulation of the corresponding
      complexes with chloride and dihydrogenphosphate.

PMID- 18802630
TI  - Computational design, synthesis and biological evaluation of para-quinone-based
      inhibitors for redox regulation of the dual-specificity phosphatase Cdc25B.
AB  - Quinoid inhibitors of Cdc25B were designed based on the Linear Combination of
      Atomic Potentials (LCAP) methodology. In contrast to a published hypothesis, the
      biological activities and hydrogen peroxide generation in reducing media of three
      synthetic models did not correlate with the quinone half-wave potential, E(1/2).

PMID- 18802631
TI  - Amine and ammonium functionalization of chloromethylsilane-ended dendrimers.
      Antimicrobial activity studies.
AB  - Novel amine- and ammonium-terminated carbosilane dendrimers of type G(n)
      [Si{CH(2)O-(C(6)H(4))-3-NMe(2)}](x) or G(n)-[Si{CH(2)O-(C(6)H(4))-3-NMe(3)(+)I(
      )}](x) have been synthesized and characterized up to second generation by
      phenolysis of (chloromethyl)silyl-terminated dendrimers with 3-dimethylamine
      phenol and subsequent quaternization with methyl iodide. Quaternized carbosilane
      dendrimers are stable in protic solvents and can be solubilised in water after
      the addition of less than 1% of dimethyl sulfoxide. A study of the antimicrobial
      activity of these cationic dendrimers of first and second generation against both
      gram-positive and gram-negative bacteria is also described. The results obtained
      demonstrate that the new ammonium-terminated carbosilane dendrimers can be
      considered as multivalent biocides.

PMID- 18802632
TI  - The mechanism of the phosphoramidite synthesis of polynucleotides.
AB  - The mechanism of the coupling step in polynucleotide synthesis using 5'-4,4'
      dimethoxytritylthymidine-3'-beta-cyanoethyl-N,N-diisopropylphosphoramidite as the
      phosphitylating agent and catalysed by the salt of saccharin and N
      methylimidazole in acetonitrile has been studied by (31)P NMR. Pre- and post
      equilibria between the activator salt and released diisopropylamine have been
      examined by (1)H NMR and ITC, which show that the salt between saccharin and
      diisopropylamine will be present in acetonitrile. Activation of the
      phosphoramidite by the salt of saccharin and N-methylimidazole involves
      nucleophilic catalysis and the formation of a reactive saccharin adduct bonded
      through its carbonyl oxygen to phosphorus. The rate constants for the reaction of
      the 4-methoxyphenol with 5'-4,4'-dimethoxytritylthymidine-3'-beta-cyanoethyl-N,N
      diisopropylphosphoramidite in the presence of saccharin-N-methylimidazole salt
      show a non-linear dependence on phenol concentration, becoming independent at
      high phenol concentrations, compatible with a change in rate limiting step from
      the alcoholysis step to the activation step.

PMID- 18802633
TI  - Direct formation of beta-glycosides of N-acetyl glycosamines mediated by rare
      earth metal triflates.
AB  - A direct, mild and efficient protocol for the preparation of beta-glycosides of N
      acetyl glucosamine (GlcNAc) and N-acetyl galactosamine (GalNAc) has been
      developed using peracetylated beta-GlcNAc and beta-GalNAc as donors. All rare
      Earth metal triflate promoters screened were found to promote glycosylation with
      Sc(OTf)(3) being superior in terms of reaction rate. Simple alcohol glycosylation
      was found to proceed smoothly in refluxing dichloromethane, whereas higher
      temperatures under microwave conditions were needed to attain acceptable yields
      with less reactive, carbohydrate based glycosyl acceptors. The protocol developed
      was applied to provide the first example of direct chemical formation of a
      disaccharide using both GlcNAc as a glycosyl donor and acceptor. The alpha
      acetate donor was found to be significantly less reactive than the corresponding
      beta-anomer necessitating higher reaction temperatures under which glycoside
      anomerisation was found to occur. It was established, that the anomerisation only
      took place in the presence of both Sc(OTf)(3) and acetic acid.

PMID- 18802634
TI  - Substituted 2-nitrobenzyltrichloroacetate esters for photodirected
      oligonucleotide detritylation in solid films.
AB  - Oligonucleotide microarray fabrication by chemical synthesis using photoacid
      generators in solid films could have advantages over existing methods, but has
      not matched the accuracy of conventional synthesis where detritylation is
      performed with acid solutions. To address this problem, we explored the kinetics
      and equilibria of nucleoside detritylation in solid films, using trichloroacetic
      acid (TCA) generated by photolysis from its esters with substituted 2-nitrobenzyl
      alcohols. We synthesised 25 such esters, all alpha-phenyl substituted, and
      assessed their potential as solid film photoacid generators. They included sets
      with (i) mono- or dimethoxy-, (ii) 5-halo-, (iii) alkyl- or aryl-substituted 5
      amino-, or (iv) 5-aryl-substituents in the 2-nitro- or 2,6-dinitrobenzyl ring.
      Absorption maxima of their UV spectra ranged from 230 to 410 nm, with quantum
      yields at 365 nm from < 0.01 to nearly 1.0. The esters formed optically clear
      solid films on glass slides without added polymer. Kinetics of intrafilm
      photoacid generation, proton activity changes and detritylation were measured in
      situ. The most effective esters for light sensitivity and detritylation were 5
      chloro-, 5-bromo-, 4,5-dimethoxy-, and 4- or 5-aryl-substituted 2,6-dinitrobenzyl
      esters. Photoacid-induced increases in proton activity and detritylation were
      severely inhibited by polymers containing electronegative heteroatoms, but not by
      polymers lacking them. In solid films, intrafilm detritylation with
      photogenerated TCA was fast, but stopped at an equilibrium well short of
      completion. Both experiment and theory emphasise the inadequacy of attempting to
      force detritylation with high intrafilm acid activity.

PMID- 18802635
TI  - Modeling the reactive properties of tandemly activated tRNAs.
AB  - Tandemly activated tRNAs, bearing amino acid moieties at both the 2'- and 3'
      positions of the 3'-terminal adenosine moiety (A(76)), have been shown to
      participate efficiently in protein synthesis [B. Wang, J. Zhou, M. Lodder, R. D.
      Anderson, III and S. M. Hecht, J. Biol. Chem., 2006, 281, 13865]. The mechanism
      by which such activated tRNAs are able to donate both amino acids to the growing
      polypeptide chain is not well understood. Here we report the chemical behavior
      and participation in protein synthesis of new bisaminoacyl derivatives of pdCpA
      and tRNA. Both amino moieties of the aminoacyl groups are shown to be important
      to enable participation in protein synthesis; paradoxically, they also confer an
      unanticipated chemical stability toward different nucleophiles. The results
      obtained suggest a model for participation of bisaminoacylated tRNAs in protein
      synthesis.

PMID- 18802636
TI  - Formation of cross-linked adducts between guanine and thymine mediated by
      hydroxyl radical and one-electron oxidation: a theoretical study.
AB  - The role of local geometric and stereo-electronic effects in tuning the
      preference for different cross-linked adducts between thymine and purinic bases
      has been analyzed by a computational approach rooted in density functional
      theory. Our study points out that G--T and T--G tandem lesions are produced
      according to the same mechanism as A--T and T--A intrastrand adducts, and in both
      cases purine--T adducts are preferred rather than the opposite sequences.
      Moreover, use of conceptual DFT tools allows the rationalization of the
      preferential occurrence of G--T and T--G tandem lesions in place of their A--T
      and T--A counterparts.

PMID- 18802637
TI  - The neomycin biosynthetic gene cluster of Streptomyces fradiae NCIMB 8233:
      genetic and biochemical evidence for the roles of two glycosyltransferases and a
      deacetylase.
AB  - An efficient protocol has been developed for the genetic manipulation of
      Streptomyces fradiae NCIMB 8233, which produces the 2-deoxystreptamine (2-DOS)
      containing aminoglycoside antibiotic neomycin. This has allowed the in vivo
      analysis of the respective roles of the glycosyltransferases Neo8 and Neo15, and
      of the deacetylase Neo16 in neomycin biosynthesis. Specific deletion of each of
      the neo8, neo15 and neo16 genes confirmed that they are all essential for
      neomycin biosynthesis. The pattern of metabolites produced by feeding putative
      pathway intermediates to these mutants provided unambiguous support for a scheme
      in which Neo8 and Neo15, whose three-dimensional structures are predicted to be
      highly similar, have distinct roles: Neo8 catalyses transfer of N
      acetylglucosamine to 2-DOS early in the pathway, while Neo15 catalyses transfer
      of the same aminosugar to ribostamycin later in the pathway. The in vitro
      substrate specificity of Neo15, purified from recombinant Escherichia coli, was
      fully consistent with these findings. The in vitro activity of Neo16, the only
      deacetylase so far recognised in the neo gene cluster, showed that it is capable
      of acting in tandem with both Neo8 and Neo15 as previously proposed. However, the
      deacetylation of N-acetylglucosaminylribostamycin was still observed in a strain
      deleted of the neo16 gene and fed with suitable pathway precursors, providing
      evidence for the existence of a second enzyme in S. fradiae with this activity.

PMID- 18802638
TI  - Engineered biosynthesis of hybrid macrolide polyketides containing D-angolosamine
      and D-mycaminose moieties.
AB  - The glycosylation of natural product scaffolds with highly modified deoxysugars
      is often essential for their biological activity, being responsible for specific
      contacts to molecular targets and significantly affecting their pharmacokinetic
      properties. In order to provide tools for the targeted alteration of natural
      product glycosylation patterns, significant strides have been made to understand
      the biosynthesis of activated deoxysugars and their transfer. We report here
      efforts towards the production of plasmid-borne biosynthetic gene cassettes
      capable of producing TDP-activated forms of D-mycaminose, D-angolosamine and D
      desosamine. We additionally describe the transfer of these deoxysugars to
      macrolide aglycones using the glycosyl transferases EryCIII, TylMII and AngMII,
      which display usefully broad substrate tolerance.

PMID- 18802639
TI  - Stereoselective cyclopropanation of serine- and threonine-derived oxazines to
      access new morpholine-based scaffolds.
AB  - A general strategy for the synthesis of novel, orthogonally protected scaffolds
      based on the unique 2-oxa-5-azabicyclo[4.1.0]heptane structure is presented. The
      described reaction sequence takes advantage of easily available starting
      materials such as serine and threonine and leads to stereochemically dense
      structures in few, high-yielding synthetic steps. We show how the stereochemistry
      can be easily tuned by starting from different beta-hydroxy-alpha-amino acids and
      also by means of a transition metal-catalyzed cyclopropanation step. The
      compounds find application as constrained templates for the construction of
      geometrically diversified libraries of compounds.

PMID- 18802640
TI  - Stereoselective synthesis of 2,4,5-trisubstituted piperidines by carbonyl ene and
      Prins cyclisations.
AB  - An approach to 2,4,5-trisubstituted piperidines is reported, in which the key
      step is the Prins or carbonyl ene cyclisation of aldehydes of the type 1. Prins
      cyclisation catalysed by concentrated hydrochloric acid in CH(2)Cl(2) at -78
      degrees C afforded good yields of two of the four possible diastereomeric
      piperidines, with the 4,5-cis product 7 predominating in a diastereomeric ratio
      of up to 94:6. The diastereoselectivity of the cyclisation decreased as the 2
      substituent increased in size, becoming unselective for very bulky 2
      substituents. In contrast, cyclisation catalysed by MeAlCl(2) in CH(2)Cl(2) or
      CHCl(3) at temperatures of between 20-60 degrees C, favoured the 4,5-trans
      diastereomer 8, in a diastereomeric ratio of up to 99:1. The low-temperature
      cyclisations catalysed by HCl proceed under kinetic control via a mechanism
      involving the development of significant carbocationic character, in which the
      4,5-cis cation is more stable than the 4,5-trans cation as a result of overlap
      with the neighbouring oxygen. The cyclisations catalysed by MeAlCl(2) proceed
      under thermodynamic control, affording the product in which both the 4- and 5
      substituents are equatorial.

PMID- 18802641
TI  - Intramolecular kinetic isotope effect in hydride transfer from dihydroacridine to
      a quinolinium ion. Rejection of a proposed two-step mechanism with a kinetically
      significant intermediate.
AB  - The intramolecular kinetic isotope effect (KIE) for hydride transfer from 10
      methyl-9,10-dihydroacridine to 1-benzyl-3-cyanoquinolinium ion has been found to
      be 5-6 by both (1)H NMR and mass spectrometry. This KIE is consistent with other
      hydride transfers. It is inconsistent with the high intermolecular KIEs derived
      by fitting to a two-step mechanism with a kinetically significant intermediate
      complex, and it is inconsistent with the strong temperature dependence of those
      KIEs. We therefore reject the two-step mechanism for this reaction, and we
      suggest that other cases proposed to follow this mechanism are in error.

PMID- 18802642
TI  - A radical-anion chain mechanism following dissociative electron transfer
      reduction of the model prostaglandin endoperoxide, 1,4-diphenyl-2,3
      dioxabicyclo[2.2.1]heptane.
AB  - The model prostaglandin endoperoxide, 1,4-diphenyl-2,3-dioxabicyclo[2.2.1]heptane
      (3), was investigated in N,N-dimethylformamide at a glassy carbon electrode using
      various electrochemical techniques. Reduction of 3 occurs by a concerted
      dissociative electron transfer (ET) mechanism. Electrolysis at -1.6 V yields 1,3
      diphenyl-cyclopentane-cis-1,3-diol in 97% by a two-electron mechanism; however,
      in competition with the second ET from the electrode, the resulting distonic
      radical-anion intermediate undergoes a beta-scission fragmentation. The rate
      constant for the heterogeneous ET to the distonic radical-anion is estimated to
      occur on the order of 2 x 10(7) s(-1). In contrast, electrolyses conducted at
      potentials more negative than -2.1 V yield a mixture of primary and secondary
      electrolysis products including 1,3-diphenyl-cyclopentane-cis-1,3-diol, 1,3
      diphenyl-1,3-propanedione, trans-chalcone and 1,3-diphenyl-1,3-hydroxypropane by
      a mechanism involving less than one electron equivalent. These observations are
      rationalized by a catalytic radical-anion chain mechanism, which is dependent on
      the electrode potential and the concentration of weak non-nucleophilic acid. A
      thermochemical cycle for calculating the driving force for beta-scission
      fragmentation from oxygen-centred biradicals and analogous distonic radical
      anions is presented and the results of the calculations provide insight into the
      reactivity of prostaglandin endoperoxides.

PMID- 18802643
TI  - Probing osmotic effects on invertase with L-(-)-sucrose.
AB  - L-(-)-sucrose was efficiently synthesized using intramolecular aglycon delivery
      and used to elucidate osmotic effects on the activity of invertase, which
      catalyzes the hydrolysis of D-(+)-sucrose. The osmotic effect imposed by L
      sucrose was responsible for more than 30% of the activity loss ascribed otherwise
      to "substrate inhibition."

PMID- 18802644
TI  - Regioselective synthesis of functionalized 3,5-diketoesters and 2,4
      diketosulfones by uncatalyzed condensation of 1-methoxy-1,3
      bis(trimethylsilyloxy)-1,3-butadienes with alpha,beta-unsaturated acid chlorides
      and sulfonyl chlorides.
AB  - The reaction of 1-methoxy-1,3-bis(trimethylsilyloxy)-1,3-butadienes with
      alpha,beta-unsaturated and functionalized acid chlorides afforded a variety of
      3,5-diketoesters which are not readily available by other methods. The reaction
      of 1-methoxy-1,3-bis(trimethylsilyloxy)-1,3-butadiene with sulfonyl chlorides
      allows a direct synthesis of 2,4-diketosulfones.

PMID- 18802645
TI  - Synthetic tetra-acylated derivatives of lipid A from Porphyromonas gingivalis are
      antagonists of human TLR4.
AB  - Tetra-acylated lipid As derived from Porphyromonas gingivalis LPS have been
      synthesized using a key disaccharide intermediate functionalized with levulinate
      (Lev), allyloxycarbonate (Alloc) and anomeric dimethylthexylsilyl (TDS) as
      orthogonal protecting groups and 9-fluorenylmethoxycarbamate (Fmoc) and azido as
      amino protecting groups. Furthermore, an efficient cross-metathesis has been
      employed for the preparation of the unusual branched R-(3)-hydroxy-13
      methyltetradecanic acid and (R)-3-hexadecanoyloxy-15-methylhexadecanoic acid of
      P. gingivalis lipid A. Biological studies have shown that the synthetic lipid As
      cannot activate human and mouse TLR2 and TLR4 to produce cytokines. However, it
      has been found that the compounds are potent antagonist of cytokine secretion by
      human monocytic cells induced by enteric LPS.

PMID- 18802646
TI  - Dendritic effects in catalysis by Pd complexes of bidentate phosphines on a
      dendronized support: Heck vs. carbonylation reactions.
AB  - Bidentate phosphine ligands have been prepared on polystyrene beads modified with
      polyether dendron spacers. When complexed to Pd(0), these systems exhibited a
      negative dendritic effect on Heck catalysis (contrary to the analogous
      monodentate phosphine systems), but mostly a positive influence on carbonylation.
      This opposite influence of the dendronization falls into line with other
      differences in the optimal ligand structure for the two reactions. The negative
      effect on the Heck catalysis with bidentate phosphines may indicate that
      dendrimer-induced reduction in the cross-linking upon Pd complexation is
      responsible for the positive effect in the corresponding monodentate phosphine
      systems.

PMID- 18802647
TI  - Diastereoselective functionalizations of enecarbamates derived from pipecolic
      acid towards 5-guanidinopipecolates as arginine mimetics.
AB  - Various substituents could be diastereoselectively introduced into the 5-position
      of pipecolic acid via electrophilic or free-radical-initiated addition to the
      carbon-carbon double bond of endocyclic enecarbamates derived from pipecolic
      acid. This study allowed the diastereoselective synthesis of both cis- and trans
      5-guanidino pipecolates, which were designed as constrained arginine mimetics and
      whose potential inhibition of nitric oxide synthase (NOS) was evaluated with
      three NOS isoforms.

PMID- 18802648
TI  - Bioisosteric replacement of the pyrazole 3-carboxamide moiety of rimonabant. A
      novel series of oxadiazoles as CB1 cannabinoid receptor antagonists.
AB  - Based on the bioisosteric replacement of the pyrazole C3-carboxamide of
      rimonabant with a 5-alkyl oxadiazole ring, a novel class of oxadiazole
      derivatives with promising biological activity towards CB1 receptors was
      discovered. Among them, compounds with an alkyl linker containing a strong
      electron-withdrawing group (e.g., CF(3)) and a sterically favorable bulky group
      (e.g., t-butyl) exhibited excellent CB1 antagonism and selectivity, and thus
      might serve as potential candidates for further development as anti-obesity
      agents.

PMID- 18802649
TI  - Effect of (5'S)-5',8-cyclo-2'-deoxyadenosine on the conformation of di and
      trinucleotides. A NMR and DFT study.
AB  - 5',8-Purine cyclonucleosides constitute an important class of oxidatively
      generated tandem lesions whose formation involves initial hydroxyl radical
      mediated hydrogen atom abstraction from the 5-hydroxymethyl group of 2
      deoxyribose followed by intramolecular cyclization. The present study deals with
      the synthesis of the 5'S diastereomer of 5',8-cyclo-2'-deoxyadenosine containing
      di- and tri-oligodeoxynucleotides as an attempt to delineate the conformational
      changes induced in the DNA fragments by the presence of a rigid modified
      nucleoside. For this purpose, extensive 1D and 2D NMR measurements that were
      completed by DFT theoretical calculations were performed. As a striking result,
      it was found that the covalent bond between C(5') and C(8) in the investigated
      purine cyclonucleoside induces an unusual West ((0)T(1)) conformation of the
      furanose ring. Thus it can be postulated that the rigid structure of the tandem
      lesion would strongly perturb the global geometry of oligonucleotides at the site
      of the modification and therefore affect the enzymatic activity of DNA
      polymerases and repair enzymes.

PMID- 18802650
TI  - Inner reorganization during the radical-biradical transition in a nor-beta
      lapachone derivative possessing two redox centers.
AB  - In this work, the electrochemical behaviour of an antitumoral nitro o-quinone
      derivative obtained from 3-bromo-nor-beta-lapachone was studied. Cyclic
      voltammetric experiments, in acetonitrile solution, revealed that both quinone
      and nitro functions are reduced independently as quasi-reversible one-electron
      transfer processes in this order. Depending on the reduction potential, a radical
      anion or a biradical dianion is obtained. The formation of these paramagnetic
      species was confirmed by performing in situ Electrochemical-Electron Spin
      Resonance (E-ESR) experiments. Analysis of the kinetics of electron transfer
      associated to those electron uptake processes, in terms of the Marcus-Hush-Levich
      model, revealed differences in the reorganization energy (lambda((k))) for both
      steps (lambda((I)): 1.07-1.11 eV; lambda((II)): 1.21-1.30 eV). By evaluating the
      conformations of the radical and biradical systems by calculations at the
      BLYP//TZVP level of theory, it was found that the inner component, for the second
      reduction process (lambda((II))) was approximately 72% of lambda((II)),
      reflecting modifications in the molecular structure during the radical anion
      biradical dianion transition. This change is also reflected in the differences
      presented by line widths of the ESR signals of both electrogenerated radical and
      diradical species.

PMID- 18802651
TI  - Total synthesis of cucurbitaxanthin A, cycloviolaxanthin and capsanthin 3,6
      epoxide by applying a regioselective ring opening of tetrasubstituted epoxides.
AB  - The synthesis of 3,6-epoxy carotenoids cucurbitaxanthin A 1, cycloviolaxanthin 2
      and capsanthin 3,6-epoxide 3, was accomplished via the C(15)-3,6-epoxides 20e and
      20f, prepared by the regioselective ring opening of the 3-hydroxy-5,6-epoxides
      10e and 10f.

PMID- 18802652
TI  - A new synthetic approach to (+)-lactacystin based on radical cyclisation of
      enantiopure alpha-ethynyl substituted serine derivatives to 4
      methylenepyrrolidinones.
AB  - Treatment of the acetylenic bromoamide 42c, derived from the enantiopure alpha
      amino alcohol 40, with Bu(3)SnH-AlBN results in an efficient 5-exo dig radical
      cyclisation to the 4-methylenepyrrolidinone 43/44 (2:1). Cleavage of the alkene
      bond in 43/44, using O(3)-Me(2)S, next gave the corresponding 4-ketopyrrolidinone
      45/46. Alpha-phenylsulfanylation of 45/46, using S-methyl-p-toluenethiosulfonate
      Et(3)N, proceeded in a stereoselective manner and led to the methylsulfanyl
      derivative 48 (ca. 9:1 selectivity). Manipulation of the functionality in 48,
      using two separate sequences, then led to the substituted pyrrolidinones 49b, 50
      and 53 which are advanced intermediates in a previous synthesis of (+)
      lactacystin 1. In related studies, the acetylenic bromoamide 28a containing all
      the carbon atoms in lactacystin was synthesised, but this substrate failed to
      undergo an anticipated radical cyclisation to the 4-methylenepyrrolidinone 30,
      analogous to 43/44. Instead, only the product of reduction of 28a, i.e. 28b, was
      produced, possibly resulting from adventitious intramolecular hydrogen
      abstraction processes from the carbon centred radical intermediate 29, i.e. 32 to
      33 and/or 31 to 34.

PMID- 18802653
TI  - Mobility limitations in persons with psychotic disorder: findings from a
      population-based survey.
AB  - BACKGROUND: There are few reports on mobility limitations in persons with
      psychotic disorder although restrictions in mobility may aggravate the general
      functional limitations of these patients. Our aim was to investigate mobility
      limitations among subjects with psychotic disorder in a general population-based
      sample. METHODS: A nationally representative sample of 6,927 persons aged 30 and
      older self-reported mobility limitations in an interview and was examined in
      performance tests. Diagnostic assessment of DSM-IV psychotic disorders combined
      SCID interview and case note data. Lifetime-ever diagnoses of psychotic disorder
      were classified into schizophrenia, other nonaffective psychotic disorders and
      affective psychoses. RESULTS: Self-reported mobility limitations were highly
      prevalent in persons with schizophrenia and other nonaffective psychosis, but not
      in the affective psychosis group. After adjusting for age and sex, persons with
      schizophrenia and other nonaffective psychoses but not affective psychoses had
      significantly increased odds of having both self-reported and test-based mobility
      limitations as well as weak muscle strength. Schizophrenia remained an
      independent predictor of mobility limitations even after controlling for
      lifestyle-related factors and chronic medical conditions. Among persons with
      nonaffective psychoses, higher levels of negative symptoms predicted mobility
      limitations. CONCLUSION: Self-reported mobility limitations are prevalent already
      at a young age in persons with schizophrenia and other nonaffective psychotic
      disorders, and among older persons with these disorders both self-reported
      limitations and measured performance tests show lower capacity in mobility.
      Difficulties in mobility are associated with negative symptoms. Mental health
      care professionals should pay attention to mobility limitations in persons with
      psychotic disorder.

PMID- 18802654
TI  - Inherited pelvic organ prolapse in the mouse: preliminary evaluation of a new
      murine model.
AB  - The objective of this study was to report the initial anatomic, radiographic, and
      genetic evaluations of a novel form of spontaneous pelvic organ prolapse (S-POP)
      in mice. We observed S-POP in a colony of UPII-SV40T transgenic mice developed
      for studies on bladder cancer. We utilized magnetic resonance imaging and
      necropsy to characterize this finding. We have established a breeding colony to
      identify inheritance patterns and for future studies. Selective breeding isolated
      the S-POP phenotype from the transgene. In contrast to other animal models, the S
      POP mouse does not require an obligatory antecedent event to manifest pelvic
      organ prolapse. Necropsy and imaging demonstrate significant displacement of the
      pelvic organs distal to the pelvic floor in both sexes. The appearance of the POP
      is similar to that seen in the human female phenotype. Preliminary breeding
      studies indicate an autosomal dominant inheritance pattern. This mouse may be an
      effective animal model for the study of POP in humans.

PMID- 18802655
TI  - Case report of tension-free vaginal tape-associated bowel obstruction and
      relationship to body habitus.
AB  - Tension-free vaginal tape (TVT) is increasingly being used as the gold standard
      to treat stress urinary incontinence. Previously reported complications include
      peritoneal perforation with acute bowel injury. A thin, petite 51-year-old woman
      with stress urinary incontinence underwent uneventful TVT placement. Three years
      later, she presented to hospital with de novo small-bowel obstruction. Laparotomy
      revealed TVT tape violating the peritoneum and causing the distal ileum to adhere
      to the pelvic sidewall. The compromised bowel was resected and primary
      anastomosis performed. Delayed, adhesion-related small-bowel obstruction can be a
      complication of TVT.

PMID- 18802656
TI  - Histotopography of the female cavernous nerve: a study using donated fetuses and
      adult cadavers.
AB  - The purpose of this study was to identify the histotopography of the female
      cavernous nerve. The study used semi-serial horizontal sections of seven fetuses
      and ten adult cadavers. In fetuses, the female cavernous nerve ran anteriorly
      between the distal vagina and the levator ani and entered the corpus cavernosum
      clitoridis. Its course through the argental hiatus was similar to that of the
      male cavernous nerve. However, the fascial arrangement along the female cavernous
      nerve was different from that of the three male fetuses included in this study.
      In female adults, the putative cavernous nerve was found running along the
      lateral aspect of the rhabdosphincter, along the superior surface of the
      urethrovaginal sphincter and around the lateral end of the latter sphincter.
      Because the female cavernous nerve and lateral vaginal wall are closely related,
      surgical treatment along the mid- and distal urethra should be conducted
      cautiously so as not to injure the perivaginal autonomic nerves.

PMID- 18802657
TI  - Sex-specific association of serum vitamin D levels with physical function in
      older adults.
AB  - In women, but not men, lower 25-hydroxyvitamin D [25(OH)D] levels were associated
      with impaired performance on two lower extremity function tests in both cross
      sectional and prospective analyses. INTRODUCTION: Preserved physical function may
      explain how 25(OH)D supplementation reduces falls and fractures. METHODS: A total
      of 1,065 community-dwelling men and women (mean age 74.6 years) with 25(OH)D
      levels and performance on timed up and go (TUG) and timed chair stand (TCS) were
      seen in 1997-1999; 769 (72%) participants returned for follow-up. Associations
      were examined using generalized linear models. RESULTS: 25(OH)D levels were
      higher in men than women, but the prevalence of vitamin D insufficiency defined
      as 25(OH)D <75 nmol/L was 14%. There were no baseline sex differences in TUG or
      TCS. However, after 2.5 years, decline in TCS and TUG was greater in women than
      men (11% vs. 3%; p < 0.001). Women in the lowest 25(OH)D quartile (<80 nmol/L)
      compared to the highest quartile had an accelerated rate of functional decline on
      the TUG and TCS independent of covariates. No significant associations were seen
      in men. CONCLUSION: In women, but not men, lower 25(OH)D levels were associated
      with impaired performance on two lower extremity function tests in both cross
      sectional and prospective analyses. These results provide additional evidence
      that 25(OH)D is associated with physical function, which may explain how vitamin
      D supplementation reduces falls and fractures.

PMID- 18802658
TI  - Morphometric vertebral fractures of the lower thoracic and lumbar spine, physical
      function and quality of life in men.
AB  - The epidemiology and sequelae of morphometric vertebral fracture (MVF) are poorly
      documented. We found that MVFs of the lower thoracic and lumbar spine were
      associated with poor quality of life and impaired physical function in men. We
      recommend that morphometric X-ray absorptiometry be included in routine requests
      for bone densitometry. INTRODUCTION: Vertebral fractures are sentinel events for
      osteoporosis. We aimed to compare quality of life and physical function in men
      with and without MVF. METHODS: Using morphometric X-ray absorptiometry (T10-L4),
      MVFs were identified in a random sample of men aged 20-93 years. Moderate and
      severe wedge, biconcave or compression deformities (>25% reduction in any
      vertebral height) were classified as MVFs. RESULTS: Of 1,147 men, MVFs were
      identified in 64. No MVFs were detected for men in their twenties. Prevalence was
      1.5% for 30-39 years, 1.4% 40-49 years, 3.2% 50-59 years, 4.7% 60-69 years, 10.0%
      70-79 years and 14.6% 80+ years. Among 555 men aged 60+ years, those with MVFs
      were twice as likely to have quality of life scores in the lowest tertile (age
      adjusted OR = 2.35, 95%CI 1.24-4.45). MVFs were associated with lower mean age
      adjusted physical activity scores [11.3 (95%CI 9.0-13.8) vs 14.0 (13.2-14.9), P =
      0.04] and longer mean age-adjusted 'Up-&-Go' times [9.5 (8.9, 10.1) vs 8.9 (8.8,
      9.1) s, P = 0.06]. CONCLUSION: Despite most men being unaware of their condition,
      MVFs were associated with poor quality of life and impaired physical function. We
      recommend that morphometric X-ray absorptiometry be included in routine requests
      for bone densitometry because detection of MVFs has important implications for
      osteoporosis management in men.

PMID- 18802659
TI  - The impact of incident fractures on health-related quality of life: 5 years of
      data from the Canadian Multicentre Osteoporosis Study.
AB  - Using prospective data from the Canadian Multicentre Osteoporosis Study (CaMos),
      we compared health utilities index (HUI) scores after 5 years of follow-up among
      participants (50 years and older) with and without incident clinical fractures.
      Incident fractures had a negative impact on HUI scores over time. INTRODUCTION:
      This study examined change in health-related quality of life (HRQL) in those with
      and without incident clinical fractures as measured by the HUI. METHODS: The
      study cohort was 4,820 women and 1,783 men (50 years and older) from the CaMos.
      The HUI was administered at baseline and year 5. Participants were sub-divided
      into incident fracture groups (hip, rib, spine, forearm, pelvis, other) and were
      compared with those without these fractures. The effects of both time and
      fracture type on HUI scores were examined in multivariable regression analyses.
      RESULTS: Men and women with hip fractures, compared to those without, had lower
      HUI measures that ranged from -0.05 to -0.25. Both women and men with spine
      fractures had significant deficits on the pain attributes (-0.07 to -0.12). In
      women, self-care (-0.06), mobility and ambulation (-0.05) were also negatively
      impacted. Women with rib fractures had deficits similar to women with spine
      fractures, and these effects persisted over time. In men, rib fractures did not
      significantly affect HUI scores. Pelvic and forearm fractures did not
      substantially influence HUI scores. CONCLUSION: The HUI was a sensitive measure
      of HRQL change over time. These results will inform economic analyses evaluating
      osteoporosis therapies.

PMID- 18802660
TI  - Heritability of impaired balance: a nationwide cohort study in twins.
AB  - SUMMARY: In this large population-based twin study, a self-estimated impaired
      balance, an important risk factor for osteoporotic fractures, had a modest
      heritability of 0.27. Individual-specific environmental influences seem to be the
      dominating cause for impaired balance. INTRODUCTION: The principal causal
      components of an osteoporotic fracture are falls and weakened bone strength.
      While bone strength has a strong genetic origin, the heritable influences on
      impaired balance that contribute to the risk of injurious falls at older age are
      uncertain. METHODS: To evaluate the heritability and environmental influence on
      self-reported impaired balance in older men and women, we used data from a sample
      of 22,998 Swedish twins, 55 to 99 years of age. RESULTS: An impaired balance was
      reported by 2,890 (12.3%) of the twins. The tetrachoric correlation for impaired
      balance was only slightly lower for like-sex dizygotic twins (0.31) compared to
      monozygotic twins (0.36). These correlations indicate a modest familial (genetic
      and shared environmental) influence. Model fitting results indicate that the age-
      and sex-adjusted heritability for impaired balance was 0.27 (95%CI = 0.01-0.45).
      Individual-specific environmental influences differed only slightly by sex and
      age. CONCLUSION: These results imply that a self-reported impaired balance, an
      independent risk factor for osteoporotic fractures, has a modestly heritable
      etiology in older subjects. Our observation can partly explain the previously
      observed modest heritability for osteoporotic fractures even though there is a
      high heritability for bone mineral density.

PMID- 18802661
TI  - Medication dosing and renal insufficiency in a pediatric cardiac intensive unit.

PMID- 18802662
TI  - Mounting device for external cerebrospinal fluid drainage: the Freiburg Stativ.
AB  - BACKGROUND: External drainage of cerebrospinal fluid (CSF) is one of the most
      common neurosurgical procedures. It is important to maintain a stable drainage
      rate, but with the commonly available mountings for CSF drainage this can be
      difficult to achieve. The drainage rate is dependent on the height-difference
      between the CSF space and the drip chamber of the device. Most mountings for open
      CSF drainage cannot be satisfactorily fixed at the bed of the patient; especially
      if the head of the bed is moved, there is a risk of over- or underdrainage.
      MATERIALS AND METHODS: We have therefore constructed a mounting for open CSF
      drainage which allows appropriate adjustment of the rate of CSF outflow, even if
      the patient's head part of the bed is moved. FINDINGS: The device was easily
      mountable or exchangeable at any hospital bed and served equally well for
      ventricular or for lumbar drainage. CONCLUSION: We think that this device can
      help to reduce serious complication of over- or underdrainage in external CSF
      drainage.

PMID- 18802663
TI  - Cytoarchitecture of Utricularia nutritive tissue.
AB  - Beginning with light microscopy studies in the late 19th century, the placental
      "nutritive tissue" in carnivorous plants of Utricularia spp. has been well
      described by several authors. Based on observations of direct contact between the
      embryo sac and the "nutritive tissue" and the lack of vascularization of the
      ovule, it has been suggested that this nutritive tissue plays a key role in the
      nutrition of the female gametophyte. To date, however, the structure of this
      tissue has received only scant attention. To fill this knowledge gap, we have
      characterized its anatomy and histochemistry in more detail and addressed the
      speculations of a number of earlier researchers. Nutritive tissue during the
      period of flower opening in three Utricularia species, each belonging to
      different sections and subgenera (Polypompholyx, Bivalvaria and Utricularia), was
      examined by light and, in particular, electron microscopy. In all of the
      investigated species, nutritive tissue cells differ from placental parenchyma
      cells in having no huge vacuole, no large amyloplasts with starch grains, and no
      protein inclusions in the nucleus. The funicular nutritive tissue in U. dichotoma
      consists of active cells with a secretory character, while U. sandersonii has a
      small placental nutritive tissue consisting of colenchymatous cells accumulating
      lipids. The most complex nutritive tissue occurs in aquatic U. intermedia, which
      occupies a derived position in the genus phylogeny. In this latter species, the
      cells of this tissue resemble meristematic cells in having a relatively large
      nucleus, thin cell walls, and reduced vacuoles, but the well-developed
      endoplasmic reticulum (ER) in some cells is similar to that in secretory cells.
      The cytoplasm is rich in microtubules, some of which are in close contact with
      the ER cisternae. We found very thick cell walls between nutritive tissue cells
      and parenchyma cells, but plasmodesmata between these types of cells are rare.
      Similarities in both the position and structure of nutritive tissue in
      Polypompholyx and section Pleiochasia support their classification together in
      one subgenus, based on results from a molecular study. The position and structure
      of the nutritive tissue in Utricularia spp. are related to the position of
      various species in the genus phylogeny.

PMID- 18802664
TI  - Obsessive compulsive disorder and migraine: case report, diagnosis and
      therapeutic approach.
AB  - Psychiatric disorders, notably mood and anxiety disorders, are frequently
      associated with migraine and chronic daily headaches. The obsessive-compulsive
      disorder (OCD) is included in the spectrum of anxiety disorders and may be a
      comorbid condition in headache patients. However, little information has been
      reported in the literature about this association. This is an important issue as
      OCD may contribute to the development or maintenance of treatment-resistant
      chronic headaches. In this paper, we describe a young female patient with
      refractory chronic migraine and OCD. Considerations on diagnosis, management and
      treatment of these comorbid conditions are presented.

PMID- 18802665
TI  - p53-dependent antiproliferative and antitumor effect of novel alkyl series of
      diorganotin(IV) compounds.
AB  - PURPOSE: A series of diorganotin(IV) dichloride complexes of N-(2
      pyridylmethylene)arylamine (nitrogen-chelating ligands) have been synthesized and
      characterized. The present study was carried out to investigate the comparative
      anti-proliferative and anti-tumor effect of Me(2)SnCl(2.)L(1) (OTC-1),
      Et(2)SnCl(2.)L(2) (OTC-2) and (n)Bu(2)SnCl. L(2) (OTC-3) in combination with X
      rays (1.5 Gy). METHOD: The cytotoxicity of these diorganotin(IV) compounds was
      studied in human peripheral lymphocytes and the antitumor activity was assessed
      in Dalton's lymphoma cells. The involvement of proteins that regulate cell cycle
      and apoptosis was investigated to elucidate the mechanism of their action.
      RESULTS: 5 mg kg(-1) of OTC-3 showed better antiproliferative and antitumor
      activity than OTC-1 and OTC-2, both as alone or in combination with X-rays. The
      maximum enhancement of exchange aberrations and the level of p53 and p16 proteins
      were observed in the OTC-3 treated samples. Upregulated expression of p53 caused
      a significant down-regulated transcriptionally repression of Survivin in OTC-3
      treated human lymphocytes. CONCLUSION: It could be possible that after treatment
      with either OTC-3 alone or in combination with X-rays the Dalton's lymphoma cells
      may die apoptotically after inducing initial delay in cell cycle and thereby
      survivality of mouse bearing Dalton's Lymphoma cells was increased significantly.

PMID- 18802666
TI  - Flexible heteroarotinoid (Flex-Het) SHetA2 inhibits angiogenesis in vitro and in
      vivo.
AB  - Flexible heteroarotinoids (Flex-Hets) compounds regulate growth, differentiation
      and apoptosis in cancer cells. The hypothesis of this study was that the lead
      Flex-Het, SHetA2, inhibits angiogenesis by blocking cytokine release from cancer
      cells. SHetA2 altered secretion of thrombospondin-4 (TSP-4), vascular endothelial
      growth factor A (VEGF) and fibroblast growth factor (bFGF) proteins from normal
      and cancerous ovarian and renal cultures. Thymidine phosphorylase (TP) expression
      was inhibited in cancer, but not normal cultures. Endothelial tube formation was
      stimulated by conditioned media from cancer but not normal cultures, and SHetA2
      reduced secretion of this angiogenic activity. SHetA2 directly inhibited
      endothelial cell tube formation and proliferation through G1 cell cycle arrest,
      but not apoptosis. Recombinant TP reversed SHetA2 anti-angiogenic activity.
      SHetA2 inhibition of in vivo angiogenesis was observed in Caki-1 renal cancer
      xenografts. In conclusion, SHetA2 inhibits angiogenesis through alteration of
      angiogenic factor secretion by cancer cells and through direct effects on
      endothelial cells.

PMID- 18802667
TI  - Structural pairwise comparisons of HLM stability of phenyl derivatives:
      Introduction of the Pfizer metabolism index (PMI) and metabolism-lipophilicity
      efficiency (MLE).
AB  - Data mining by pairwise comparison of over 150,000 human liver microsome (HLM)
      intrinsic clearance values stored within the internal Pfizer database has been
      performed by an automated tool. Systematic probability tables of specific
      structural changes on the intrinsic clearance of phenyl derivatives have been
      generated. From these data two new parameters, the Pfizer Metabolism Index (PMI)
      and Metabolism-Lipophilicity Efficiency (MLE) are introduced for each fragment.
      The findings are applied to a Topliss style analysis that focuses on metabolic
      stability.

PMID- 18802668
TI  - A comparison of hypoglycemic activity of three species of basidiomycetes rich in
      vanadium.
AB  - The hypoglycemic activity of fermented mushroom of three fungi of basidiomycetes
      rich in vanadium was studied in this paper. Alloxan- and adrenalin-induced
      hyperglycemic mice were used in the study. The blood glucose and the sugar
      tolerance were determined. After the mice were administered (ig) with Coprinus
      comatus rich in vanadium, the blood glucose of alloxan-induced hyperglycemic mice
      decreased (p < 0.05), ascension of blood glucose induced by adrenalin was
      inhibited (p < 0.01) and the sugar tolerance of the normal mice was improved.
      However, the same result did not occur in Ganoderma lucidum and Grifola frondosa
      group. Compared with Ganoderma rich in vanadium and Grifola frondosa rich in
      vanadium, the hypoglycemic effects of Coprinus comatus rich in vanadium on
      hyperglycemic animals are significant; it may be used as a hypoglycemic food or
      medicine for hyperglycemic people.

PMID- 18802669
TI  - Stabilized-solubilized ferric pyrophosphate as a new iron source for food
      fortification. Bioavailability studies by means of the prophylactic-preventive
      method in rats.
AB  - The purpose of the present work was to evaluate the iron bioavailability of a new
      ferric pyrophosphate salt stabilized and solubilized with glycine. The
      prophylactic-preventive test in rats, using ferrous sulfate as the reference
      standard, was applied as the evaluating methodology both using water and yogurt
      as vehicles. Fifty female Sprague-Dawley rats weaned were randomized into five
      different groups (group 1: FeSO(4); group 2: pyr; group 3: FeSO(4) + yogurt;
      group 4: pyr + yogurt and group 5: control). The iron bioavailability (BioFe) of
      each compound was calculated using the formula proposed by Dutra-de-Oliveira et
      al. where BioFe % = (HbFef - HbFei) x 100/ToFeIn. Finally, the iron
      bioavailability results of each iron source were also given as relative
      biological value (RBV) using ferrous sulfate as the reference standard. The
      results showed that both BioFe % and RBV % of the new iron source tested is
      similar to that of the reference standard independently of the vehicle employed
      for the fortification procedure (FeSO(4) 49.46 +/- 12.0% and 100%; Pyr 52.66 +/-
      15.02% and 106%; FeSO(4) + yogurth 54.39 +/- 13.92% and 110%; Pyr + yogurt 61.97
      +/- 13.54% and 125%; Control 25.30 +/- 6.60, p < 0.05). Therefore, the stabilized
      and soluble ferric pyrophosphate may be considered as an optimal iron source for
      food fortification.

PMID- 18802670
TI  - Effects of lanthanum chloride administration in prenatal stage on one-trial
      passive avoidance learning in chicks.
AB  - Lanthanum cations (La 3+) are well known for their inhibitory actions on calcium
      channels. Prenatal lanthanum exposure may affect the development of embryo and
      alter the capacity for learning and memory in adults, and the one-trial passive
      avoidance learning paradigm with day-old chicks is an excellent model to study
      several mechanisms of memory formation. In the present study, we examined the
      effects of prenatal lanthanum chloride exposure on memory consolidation using one
      trial passive avoidance learning task in day-old chicks. The data suggest that
      chicks injected with lanthanum chloride (2 mg/kg) daily from E9 to E16 had
      significantly impaired long-term memory at 120 min after training (p < 0.05) but
      not the chicks injected with lanthanum chloride (0.1 mg/kg) daily from E9 to E16.

PMID- 18802671
TI  - Role of oxidative stress, apoptosis, and intracellular homeostasis in primary
      cultures of rat proximal tubular cells exposed to cadmium.
AB  - Cadmium (Cd) is a known nephrotoxic element. In this study, the primary cultures
      of rat proximal tubular (rPT) cells were treated with low doses of cadmium
      acetate (2.5 and 5 microM) to investigate its cytotoxic mechanism. A progressive
      loss in cell viability, together with a significant increase in the number of
      apoptotic and necrotic cells, were seen in the experiment. Simultaneously,
      elevation of intracellular [Ca(2+)]i and reactive oxygen species (ROS) levels,
      significant depletion of mitochondrial membrane potential(Delta Psi) and cellular
      glutathione (GSH), intracellular acidification, and inhibition of Na(+), K(+)
      ATPase and Ca(2+)-ATPase activities were revealed in a dose-dependent manner
      during the exposure, while the cellular death and the apoptosis could be markedly
      reversed by N-acetyl-L-cysteine (NAC). Also, the calcium overload and GSH
      depletion were significantly affected by NAC. In conclusion, exposure of rPT
      cells to low-dose cadmium led to cellular death, mediated by an apoptotic and a
      necrotic mechanism. The apoptotic death might be the chief mechanism, which may
      be mediated by oxidative stress. Also, a disorder of intracellular homeostasis
      induced by oxidative stress and mitochondrial dysfunction is a trigger of
      apoptosis in rPT cells.

PMID- 18802672
TI  - Maternal milk concentration of zinc, iron, selenium, and iodine and its
      relationship to dietary intakes.
AB  - The dietary intake of zinc (Zn), iron (Fe), selenium (Se), and iodine (I) of 31
      lactating Mexican-American women attending the Hidalgo County WIC program in Rio
      Grande Valley (RGV), Texas was estimated from 24-h dietary recall interviews.
      Milk samples were obtained from lactating mothers who had infants 3 months of age
      and younger. Milk samples were collected in two visits to assess change in breast
      milk composition after 1-3 months postpartum: group A--after 30-45 days and group
      B--75-90 days. Dietary intakes indicated that the study participants had
      significantly inadequate percent energy intakes than the DRI (Dietary Recommended
      Intakes) percent recommended kilocalorie values but protein intakes were
      substantially higher than the percent recommended values. The estimated percent
      Zn, Fe, Se, and I intakes were also significantly lower than the DRI percent
      recommended values. The lactating mothers consumed significantly less Zn, Se, and
      I when compared to the Recommended Dietary Allowances (RDA) even though Fe intake
      was higher than the RDA value. Breast milk concentration of Zn, Fe, and Se were
      in agreement within the range of representative values for Constituents of Human
      Milk but I has significantly less concentration than the representative value.
      There was no statistically significant correlation observed between dietary
      intake and milk concentration of Zn, Fe, Se, and I. This study compares the
      estimated dietary intake of zinc, iron, selenium, and iodine to the concentration
      of these trace elements in the maternal milk of lactating women of Mexican
      American heritage who attend the Rio Grande Valley WIC clinic.

PMID- 18802673
TI  - Concentrations of selected essential and non-essential elements in blood of
      harbor seal (Phoca vitulina) pups of the German North Sea.
AB  - This study on harbor seal (Phoca vitulina) pups of the North Sea evaluated
      concentrations of 14 essential and non-essential elements (Al, As, Be, Ca, Cd,
      Cr, Fe, Mn, Mo, Ni, Pb, Se, Sn, and Zn) in whole blood samples. The essential
      elements are analyzed to give references for health status determinations of
      pups. The measurement of classic toxic metals, like Pb or Cd, and other elements
      that may be in toxic concentrations in blood, is important due to their influence
      on health, particularly on the immune system. Blood samples of six seal pups
      found on the German Wadden Sea coast of Schleswig-Holstein in 2004 and
      transported to the Seal Centre Friedrichskoog, Germany were collected. The blood
      sampling was performed three times, immediately after collection of the newborns,
      after 1.5 months, and after 2 months before their release back into the wild.
      Inductively coupled plasma mass spectrometry and total reflection X-ray
      fluorescence spectrometry were used to determine the element concentrations. We
      found higher concentrations of Al, As, Fe, Mo, and Zn in blood samples of
      newborns compared to samples collected later, probably due to transplacental and
      lactational transfer from mother to fetus. Furthermore, there is a high need for,
      in particular, Fe and Zn in the developing organism, which may cause reduced
      values after some month. In contrast, the concentrations of Be, Cd, Ca, Cr, Pb,
      Mn, Ni, Se, and Sn, which were low in newborns and increased during the study,
      may be due to the fish fed to infant pups. Compared to free-ranging adults, in
      pups, the concentrations of Al, Ni, and Pb were higher in contrast to lower
      concentrations of As, Mn, and Mo. This case study is the first report on element
      levels in harbor seal pups of the North Sea.

PMID- 18802674
TI  - Effects of chromium picolinate on oxidative damage in primary piglet hepatocytes.
AB  - Chromium picolinate is a popular nutritional supplement whose safety has been
      questioned because of the potential risk of oxidative DNA damage. To investigate
      this possibility, a dose-dependent study was performed in piglet hepatocyte
      cultures in which low (8 microM), medium (200 microM), and high (400 microM)
      doses of chromium picolinate were tested and compared to untreated controls.
      After 48 h incubation, there were no significant differences in the levels of
      intracellular reactive oxygen species, medium lactate dehydrogenase activity, and
      comet indicators between the three experimental groups and controls (p > 0.05).
      In the 8 microM-treated group, the intracellular malondialdehyde content was
      significantly decreased relative to controls (p < 0.05). All of the studied
      parameters showed a dose-dependent increase that was statistically significant
      between the low and high doses (p < 0.05). These results suggest that: (1)
      chromium picolinate may affect the oxidative status of piglet hepatocytes; (2)
      the appropriate dose (approximately physiological concentration) of chromium
      picolinate can inhibit lipid peroxidation, and (3) high doses of chromium
      picolinate have no significant effects on oxidative damage in piglet hepatocytes,
      but the existing evidence also imply that exposure to a higher dose appears to be
      unwarranted.

PMID- 18802675
TI  - DNA sequencing-based typing of HPA-1 to HPA-17w systems.
AB  - Although several DNA-based human platelet antigens (HPA) typing techniques, such
      as PCR-SSP and PCR-SSO, have been established, the typing errors and the lack of
      interlaboratory reproducibility are still the issues of concerns. In the present
      study, polymerase chain reaction primers were designed for identification of all
      the phenotypically different HPA-1 to HPA-17w types by sequencing-based typing
      (SBT) method using genomic DNA samples. No discrepancies were observed between
      PCR-SSP typing and SBT typing in typing a panel of HPA-typed platelet donors that
      included all common HPA types and the rare HPA-1b, 2b, 3b, and 6bw homozygous
      donors.

PMID- 18802676
TI  - Clinical variability in distal spinal muscular atrophy type 1 (DSMA1):
      determination of steady-state IGHMBP2 protein levels in five patients with
      infantile and juvenile disease.
AB  - Distal spinal muscular atrophy type 1 (DSMA1) is caused by mutations in the
      immunoglobulin mu-binding protein 2 (IGHMBP2) gene. Patients with DSMA1 present
      between 6 weeks and 6 months of age with progressive muscle weakness and
      respiratory failure due to diaphragmatic palsy. Contrary to this "classic"
      infantile disease, we have previously described a DSMA1 patient with juvenile
      disease onset. In this paper, we present (1) a second juvenile case and (2) the
      first study of DSMA1 on protein level in patients with infantile (n = 3) as well
      as juvenile (n = 2) disease onset observing elevated residual steady-state
      IGHMBP2 protein levels in the patients with late onset DSMA1 as compared to those
      with classic DSMA1. Mutation screening in IGHMBP2 revealed two patients compound
      heterozygous for a novel missense mutation (c.1478C-->T; p.T493I) and another
      previously described mutation. In lymphoblastoid cells of both patients, steady
      state IGHMBP2 protein levels were reduced. In comparison to wild-type IGHMBP2,
      the p.T493I variant protein had an increased tendency to aggregate and
      spontaneously degrade in vitro. We verified a change in the physicochemical
      properties of the p.T493I variant which may explain the pathogenicity of this
      mutation. Our data further suggest that the age of onset of DSMA1 is variable,
      and we discuss the effect of residual IGHMBP2 protein levels on the clinical
      course and the severity of the disease.

PMID- 18802677
TI  - Malic enzyme is present in mouse islets and modulates insulin secretion.
AB  - AIMS/HYPOTHESIS: The pyruvate-malate shuttle is a metabolic cycle in pancreatic
      beta cells and is important for beta cell function. Cytosolic malic enzyme (ME)
      carries out an essential step in the shuttle by converting malate to pyruvate and
      generating NADPH. In rat islets the pyruvate-malate shuttle may regulate insulin
      secretion and it has been shown to play a critical role in adaptation to obesity
      and insulin resistance. However, ME has not been demonstrated in mouse islets and
      three reports indicate that mouse islets contain no ME activity. If mouse islets
      lack ME, rat and mouse islets must regulate insulin secretion by different
      mechanisms. METHODS: We measured ME activity by a fluorometric enzymatic assay
      and Me mRNA by real-time PCR. ME activity was also measured in streptozotocin
      treated mouse islets. FACS-purified beta cells were obtained from MIP-GFP mouse
      islets, agouti-L obese mouse islets and mouse beta cell line MIN-6. Insulin
      secretion and NADPH/NADP(+) ratios were measured in Me siRNA-treated beta cells.
      RESULTS: ME activity and Me mRNA were present in C57BL/6 mouse islets. ME
      activity was reduced in streptozotocin-treated mouse islets. ME activity was also
      measurable in FACS-purified mouse beta cells. In addition, ME activity was
      significantly increased in obese agouti-L mouse islets and the mouse MIN-6 cell
      line. Me siRNA inhibited ME activity and reduced glucose-stimulated insulin
      secretion and also inhibited NADPH products. CONCLUSIONS/INTERPRETATION: Mouse
      islets contain ME, which plays a significant role in regulating insulin
      secretion.

PMID- 18802678
TI  - Mitochondrial fitness and insulin sensitivity in humans.
AB  - Human mitochondria can be studied either in biopsies or by measuring flux through
      ATP synthase and phosphocreatine recovery using magnetic resonance spectroscopy.
      Myocellular ATP production (flux through ATP synthase [fATP]) increases by up to
      90% during 8 h of insulin stimulation. Fasting mitochondrial function is 14-40%
      lower than in controls in the presence of insulin resistance, as seen in those
      with type 2 diabetes, their insulin-resistant relatives or the obese. Insulin
      stimulated fATP is abolished in insulin-resistant relatives and patients with
      type 2 diabetes, and patients frequently show decreased mitochondrial
      size/density. Age, fat mass, physical activity, plasma NEFA and glucose all
      correlate negatively with mitochondrial function, but it is for methodological
      reasons difficult to determine whether reduced mitochondrial content or function
      account for reduced ATP production in insulin resistance. Experimental plasma
      NEFA elevation appears to inhibit mitochondrial function by interfering with the
      metabolic actions of insulin, which might explain impaired mitochondrial function
      in obesity. Alternatively, primary mitochondrial abnormalities, as seen in those
      with inherited risk of type 2 diabetes, could decrease lipid oxidation, thereby
      raising circulating and intracellular NEFA levels. In type 2 diabetes, chronic
      hyperglycaemia and dyslipidaemia could first diminish the function, and
      subsequently reduce the size or density of mitochondria via oxidative stress and
      apoptosis. Many questions remain unsolved, including (1) which mechanisms
      regulate mitochondrial adaptation to nutrient overload; (2) what factors control
      the expression of genes encoding mitochondrial proteins and other signals
      involved in mitochondrial biogenesis; (3) which geno/phenotypes are associated
      with both insulin resistance and mitochondrial abnormalities; and (4) which are
      the most promising targets for improving mitochondrial fitness in insulin
      resistance?

PMID- 18802679
TI  - Inducible nitric oxide synthase gene deficiency counteracts multiple
      manifestations of peripheral neuropathy in a streptozotocin-induced mouse model
      of diabetes.
AB  - AIMS/HYPOTHESIS: Evidence for the importance of peroxynitrite, a product of
      superoxide anion radical reaction with nitric oxide, in peripheral diabetic
      neuropathy is emerging. The role of specific nitric oxide synthase isoforms in
      diabetes-associated nitrosative stress and nerve fibre dysfunction and
      degeneration remains unknown. This study evaluated the contribution of inducible
      nitric oxide synthase (iNOS) to peroxynitrite injury to peripheral nerve and
      dorsal root ganglia and development of peripheral diabetic neuropathy. METHODS:
      Control mice and mice with iNos (also known as Nos2) gene deficiency (iNos ( -/-
      )) were made diabetic with streptozotocin, and maintained for 6 weeks.
      Peroxynitrite injury was assessed by nitrotyrosine and poly(ADP-ribose)
      accumulation (immunohistochemistry). Thermal algesia was evaluated by paw
      withdrawal, tail-flick and hot plate tests, mechanical algesia by the Randall
      Selitto test, and tactile allodynia by a von Frey filament test. RESULTS:
      Diabetic wild-type mice displayed peroxynitrite injury in peripheral nerve and
      dorsal root ganglion neurons. They also developed motor and sensory nerve
      conduction velocity deficits, thermal and mechanical hypoalgesia, tactile
      allodynia and approximately 36% loss of intraepidermal nerve fibres. Diabetic
      iNos ( -/- ) mice did not display nitrotyrosine and poly(ADP-ribose) accumulation
      in peripheral nerve, but were not protected from nitrosative stress in dorsal
      root ganglia. Despite this latter circumstance, diabetic iNos ( -/- ) mice
      preserved normal nerve conduction velocities. Small-fibre sensory neuropathy was
      also less severe in diabetic iNos ( -/- ) than in wild-type mice.
      CONCLUSIONS/INTERPRETATION: iNOS plays a key role in peroxynitrite injury to
      peripheral nerve, and functional and structural changes of diabetic neuropathy.
      Nitrosative stress in axons and Schwann cells, rather than dorsal root ganglion
      neurons, underlies peripheral nerve dysfunction and degeneration.

PMID- 18802680
TI  - Cognitive and interpersonal predictors of stress generation in children of
      affectively ill parents.
AB  - Stress generation is a process in which individuals, through their depressive
      symptoms, personal characteristics, and/or behaviors, contribute to the
      occurrence of stressful life events. While this process has been well documented
      in adults, few studies have examined it in children. The present study examines
      whether cognitive and interpersonal vulnerability factors to depression
      contribute to stress generation in children, independent of their current
      depressive symptoms. Participants included 140 children (ages 6 to 14) and one of
      their parents. During an initial assessment, children completed self-report
      measures assessing cognitive and interpersonal vulnerability factors to
      depression. Children and their parents also completed measures assessing
      depressive symptoms. One year later, children and their parents participated in a
      semi-structured interview assessing the occurrence of stressful life events in
      the past year. Multi-level modeling results provided strong support for the
      stress generation process in children of affectively ill parents and highlight
      the importance of considering gender and age moderation effects.

PMID- 18802681
TI  - Lithium dilution cardiac output measurement in the critically ill patient:
      determination of precision of the technique.
AB  - BACKGROUND: Lithium dilution cardiac output by LiDCOplus (LiDCO, Cambridge, UK)
      is a validated methodology for measuring cardiac output. It is used to calibrate
      a pulse pressure analysis algorithm (PulseCO) for the continuous measurement of
      subsequent changes in this variable. The variability of measurements, or
      precision, within patients of lithium dilution cardiac output has not previously
      been described. MATERIAL AND METHODS: Thirty-five hemodynamically stable patients
      in intensive care, with no significant variability in heart rate, mean arterial
      pressure or central venous pressure, were recruited. Fifty-three determinations
      of cardiac output were made, each using four lithium dilution measurement curves
      performed consecutively within a maximum period of 10 min. The coefficient of
      variation of the measurements was determined and used to derive the least
      significant change in cardiac output that this technique could reliably detect.
      RESULTS: For a single measurement, the coefficient of variation was 8%. This
      equates to the technique being able to detect a change (least significant change)
      between two measurements of 24%. Averaging two lithium dilution measurements
      improved the coefficient of variation to 6% with a least significant change of
      17%. Using the average of three curves reduced the coefficient of variation to 5%
      with a least significant change of 14%. CONCLUSIONS: To achieve a good precision
      with this technique, three lithium dilution measurements should be averaged. This
      will allow changes in cardiac output of more than 14% to be reliably detected.
      The understanding of the precision of this technique allows the user to know when
      a real change has happened to their patient.

PMID- 18802683
TI  - Disseminated intravascular coagulation score is associated with mortality for
      children with shock.
AB  - OBJECTIVE: To evaluate the association between disseminated intravascular
      coagulation (DIC) score and mortality for children with shock. DESIGN:
      Retrospective. SETTING: Tertiary care, 20-bed pediatric intensive care unit.
      PATIENTS: A total of 132 children with sepsis or shock admitted from January 2003
      to December 2005. MEASUREMENTS AND RESULTS: A total of 132 patients less than 18
      years of age with a diagnosis of shock or sepsis were included in the analysis.
      Of these patients, 90 survived and 42 died (31.8%). Patients ranged from 6 days
      to 18 years (median 5.8 years), and were a majority male (63%). Variables
      associated with mortality included peak DIC score within 24 h of ICU admission,
      age, weight, volume of blood products transfused, inotrope score, pediatric index
      of mortality (PIM 2) score, 12-h pediatric risk of mortality (PRISM III) score
      and presence of mechanical ventilation (P < 0.05). Patients with DIC scores >or=
      5 (overt DIC) had 50% mortality, compared to 20% for patients with DIC scores <
      5. Overall, a one-point rise in DIC score was associated with an increased risk
      of mortality after adjusting for age, race, gender, hemodynamic instability, and
      PRISM III score [OR 1.35 (1.02, 1.78)]. Most patients achieve their peak DIC
      score within 2 h of ICU admission. CONCLUSIONS: This analysis suggests that DIC
      score, easily calculated early in ICU admission, is associated with mortality for
      children with sepsis and shock, regardless of initial severity of illness or
      inotrope use.

PMID- 18802684
TI  - Chronic sleep disorders in survivors of the acute respiratory distress syndrome.
AB  - PURPOSE: Sleep disruption is well recognized in the Intensive Care Unit. Poor
      sleep quality likely continues following discharge from hospital in several
      patients and becomes a chronic disorder in some. The aim of this study was to
      describe the etiology of chronic sleep complaints in survivors of ARDS. METHODS:
      Seven ARDS survivors with no previous sleep complaints who reported difficulty
      sleeping 6 months or more following discharge from hospital were evaluated. Sleep
      quality was assessed subjectively with a sleep history and the Insomnia Severity
      Index and objectively with polysomnography. Daytime sleepiness was assessed with
      the Epworth Sleepiness Scale. RESULTS: A chronic sleep disorder was identified in
      each patient who reported difficulty sleeping. The primary sleep disorder was
      chronic conditioned insomnia (5 patients), parasomnia (1 patient) and obstructive
      sleep apnea (1 patient). In addition, 4 patients had periodic leg movements,
      which was of uncertain clinical significance. CONCLUSION: Chronic sleep
      disorders, which originate during the acute illness, are present in some ARDS
      survivors several months after discharge from hospital. If unrecognized, lack of
      treatment may contribute to impaired quality of life and incomplete
      rehabilitation from their critical illness.

PMID- 18802685
TI  - Regional cooling of the extracorporeal blood circuit: a novel anticoagulation
      approach for renal replacement therapy?
AB  - OBJECTIVE: To test the hypothesis that cooling of blood in the extracorporeal
      circuit of continuous veno-venous hemofiltration (CVVH) enables to realize the
      procedure without the need of anticoagulation. DESIGN: Experimental animal study.
      METHODS: We developed the device for selective cooling of extracorporeal circuit
      (20 degrees C) allowing blood rewarming (38 degrees C) just before returning into
      the body. Twelve anesthetized and ventilated pigs were randomized to receive
      either 6 h of CVVH with application of this device (COOL; n = 6) or without it
      (CONTR; n = 6). MEASUREMENTS: Before the procedure and in 15, 60, 180, 360 min
      after starting hemofiltration variables related to: (1) circuit patency [time to
      clotting (TC), number of alarm-triggered pump stopping (AS), venous and
      transmembranous circuit pressures (VP, TMP)], (2) coagulation status in the
      extracorporeal circuit [thrombin-antithrombin complexes (TAT(circ)),
      thromboelastography (TEG)] and (3) animal status (hemodynamics, hemolysis and
      biochemistry) were assessed. RESULTS: The patency of all circuits treated with
      selective cooling was well maintained within the observation period. By contrast,
      five of six sessions were prematurely clotted in the untreated group. As a
      result, the number of AS was significantly higher in the CONTR group. In-circuit
      thrombus generation in CONTR group was associated with a markedly increasing
      TAT(circ). TEG performed at 180 min of the procedure revealed a tendency to a
      prolonged initial clotting time and a significant decrease in clotting rate of in
      circuit blood in the COOL group. No signs of repeated cooling/rewarming-induced
      hemolysis were observed in animals treated with "hypothermic circuit" CVVH.
      CONCLUSION: In this porcine model, regional extracorporeal blood cooling proved
      effective in preventing in-circuit clotting without the need to use any other
      anticoagulant.

PMID- 18802686
TI  - Substance dependence and psychiatric disorders are related to outcomes in a mixed
      ICU population.
AB  - OBJECTIVE: Substance dependence disorders are common in hospitalized patients and
      are associated with poor recovery. We compared mortality and discharge
      disposition in critically ill patients with and without substance dependence and
      patients with and without psychiatric disorders. We also compared the prevalence
      of substance dependence and psychiatric disorders to population data. METHODS:
      All medical records of shock trauma intensive care unit (ICU) patients (mixed
      medical and surgical) at LDS Hospital were reviewed for pre-critical illness
      alcohol dependence, drug dependence, and psychiatric disorders. RESULTS: There
      were 742 critically ill patients of whom 54% were male, acute respiratory
      distress syndrome developed in 5.5% and hospital mortality was 21%. The mean
      acute physiology and chronic health evaluation II scores were 16.5 +/- 7.9,
      sequential organ failure assessment scores were 6.7 +/- 4.2, duration of
      mechanical ventilation was 5 +/- 6.2 days, ICU length of stay (LOS) was 7.3 +/-
      10.1 days, hospital LOS was 12.3 +/- 12.9 days. Multivariable regression analyses
      found psychiatric disorders predicted higher hospital mortality (Odds ratio =
      1.50), but was not statistically significant (p = 0.08); substance dependence
      predicted shorter hospital LOS (R ( 2 ) = 0.08, p = 0.01) after controlling for
      covariates. There was a higher prevalence of substance dependence compared to
      Utah (p < 0.001) and US population data (p < 0.001). The prevalence of
      psychiatric disorders was significantly lower in our patients compared to US
      population data (19 vs. 26%, p < 0.001). CONCLUSIONS: Our data suggest that
      substance dependence increases hospital LOS and that patients with drug or
      alcohol dependence are at higher risk for ICU admission compared to the general
      population.

PMID- 18802687
TI  - Psychiatric disorders and the ICU: gaps and opportunities.

PMID- 18802688
TI  - Renal resistive index and renal function before and after paracentesis in
      patients with hepatorenal syndrome and tense ascites.
AB  - OBJECTIVE: To assess the effect of reducing intra-abdominal pressure (IAP) by
      paracentesis on renal resistive index (RI), hemodynamics and renal function.
      DESIGN AND SETTING: Uncontrolled trial in a university gastroenterological
      intensive care unit. PATIENTS: Twelve spontaneously breathing cirrhotic patients
      with hepatorenal syndrome, tense ascites and a clinical indication for
      paracentesis. INTERVENTIONS: Paracentesis and substitution of albumin.
      MEASUREMENTS AND RESULTS: Hemodynamic variables were assessed by transpulmonary
      thermodilution, RI was determined by Doppler ultrasound of renal interlobar
      arteries. After paracentesis and albumin substitution, there was a significant
      decrease of IAP (20 mmHg (19-22) to 12 mmHg (10-13), systemic vascular resistance
      index (from 1,243 dyn s/cm(5)/m(2) (1,095-1,745) to 939 dyn s/cm(5)/m(2) (812
      1,365); p = 0.005) and RI (from 0.848 (0.810-0.884) to 0.810 (0.780-0.826); p =
      0.003). Arterial compliance increased from 1.33 mL/mmHg (0.89-1.74) to 1.71
      mL/mmHg (1.21-2.12), pulse pressure index remained unchanged. Creatinine
      clearance (ClCreat) increased significantly from 5 mL/min (0-28) to 9 mL/min (0
      36) (p = 0.018) and urinary output from 12 mL/h (0-49) to 16 mL/h (0-64) (p =
      0.043). CONCLUSIONS: In patients with cirrhosis, HRS and tense ascites, IAP may
      contribute to renal dysfunction. Reduction of IAP following paracentesis and
      albumin substitution may improve ClCreat, probably by improving renal blood flow
      as reflected by decreasing RI in Doppler ultrasound.

PMID- 18802689
TI  - Biomechanics of the meniscus-meniscal ligament construct of the knee.
AB  - The menisci of the knee act primarily to redistribute contact force across the
      tibio-femoral articulation. This meniscal function is achieved through a
      combination of the material, geometry and attachments of the menisci. The main
      ligaments that attach the menisci to the tibia (insertional ligaments, deep
      medial collateral ligament), the femur (meniscofemoral ligaments, deep medial
      collateral ligament) and each other (the anterior intermeniscal ligament) are the
      means by which the contact force between tibia and femur is distributed into hoop
      stresses in the menisci to reduce contact pressure at the joint. This means that
      the functional biomechanics of the menisci cannot be considered in isolation and
      should be considered as the functional biomechanics of the meniscus-meniscal
      ligament construct. This article presents the current knowledge on the anatomy
      and functional biomechanics of the meniscus and its associated ligaments. Much is
      known about the function of the meniscus-meniscal ligament construct; however,
      there still remain significant gaps in the literature in terms of the properties
      of the anterior intermeniscal ligament and its function, the properties of the
      insertional ligaments, and the most appropriate ways to reconstruct meniscal
      function surgically.

PMID- 18802690
TI  - Cross-flow microfiltration system for rapid enrichment of bacteria in water.
AB  - Permanent monitoring of waterborne pathogens is important for securing the
      hygiene of water. Enumerating bacteria in water at low concentrations and minute
      quantities demands rapid and efficient enrichment methods in order to improve the
      signal-to-noise ratio of subsequent determination methods. In this work an
      automated cross-flow microfiltration (CFM) system is presented which is usable in
      the field to concentrate large volumes of environmental water for analytical
      purposes. It was designed as a rapid enrichment apparatus achieving high recovery
      and high concentration factors. The efficiency of the CFM system was studied for
      E. coli spiked in a 10-L tap water sample. By this technique, a 10-L water sample
      was concentrated by a factor of 200 in 15 min. The high and consistent recovery
      of 91.3 +/- 5.4% living cells in the concentration range 0.01 and 100 cfu mL(-1)
      is suitable for rapid enumeration of bacteria in water.

PMID- 18802691
TI  - Materials and techniques for coiling of cerebral aneurysms: how much scientific
      evidence do we have?
AB  - INTRODUCTION: Since coils were approved for aneurysm treatment, materials and
      techniques developed rapidly. It still remains an open question whether one
      material or method is superior. This article reviews the literature on various
      coil types and treatment approaches assessing the scientific evidence of its use.
      MATERIALS AND METHODS: Studies on aneurysm treatment with Guglielmi detachable
      platinum coils, bioactive coils, hydrogel coated coils, and complex designs as
      well as balloon- and stent-assisted techniques were retrieved by a PubMed
      database search from 1990 until May 2008. Data were analyzed in terms of aneurysm
      occlusion, permanent morbidity and mortality, recanalization, and retreatment. We
      also assessed the level of evidence of the published studies. RESULTS: Only the
      International Subarachnoid Aneurysm Trial provides level I evidence proving the
      superiority of endovascular over surgical therapy in ruptured aneurysms.
      Randomized trials comparing bioactive or hydrogel coated devices with bare coils
      are ongoing. Other studies were based on registries or case series mainly
      conducted without control groups. Morbidity, mortality, and initial occlusion
      rates appear similar for all devices. No clear evidence exists for the
      superiority of bioactive- or hydrocoils regarding long-term stability. It remains
      ambiguous whether morbidity and mortality rises with the use of balloons and
      stents. There is no evidence that routine use of balloons improves treatment
      durability. Mid-term results of stent-assisted coiling of complex aneurysms
      appear favorable. CONCLUSION: There is a lack of studies with a high level of
      evidence comparing different coiling materials and techniques. Case series and
      registries were not able to prove the superiority of any device or method.

PMID- 18802692
TI  - Proline as a stress protectant in yeast: physiological functions, metabolic
      regulations, and biotechnological applications.
AB  - Proline is an important amino acid in terms of its biological functions and
      biotechnological applications. In response to osmotic stress, proline is
      accumulated in many bacterial and plant cells as an osmoprotectant. However, it
      has been shown that proline levels are not increased under various stress
      conditions in the yeast Saccharomyces cerevisiae cells. Proline is believed to
      serve multiple functions in vitro such as protein and membrane stabilization,
      lowering the T (m) of DNA, and scavenging of reactive oxygen species, but the
      mechanisms of these functions in vivo are poorly understood. Yeast cells
      biosynthesize proline from glutamate in the cytoplasm via the same pathway found
      in bacteria and plants and also convert excess proline to glutamate in the
      mitochondria. Based on the fact that proline has stress-protective activity, S.
      cerevisiae cells that accumulate proline were constructed by disrupting the PUT1
      gene involved in the degradation pathway and by expressing the mutant PRO1 gene
      encoding the feedback inhibition-less sensitive gamma-glutamate kinase to enhance
      the biosynthetic activity. The engineered yeast strains successfully showed
      enhanced tolerance to many stresses, including freezing, desiccation, oxidation,
      and ethanol. However, the appropriate cellular level and localization of proline
      play pivotal roles in the stress-protective effect. These results indicate that
      the increased stress protection is observed in yeast cells under the artificial
      condition of proline accumulation. Proline is expected to contribute to yeast
      based industries by improving the production of frozen dough and alcoholic
      beverages or breakthroughs in bioethanol production.

PMID- 18802693
TI  - Hyper production of cellulase-free xylanase by Thermomyces lanuginosus SSBP on
      bagasse pulp and its application in biobleaching.
AB  - A cellulase-free xylanase production by Thermomyces lanuginosus SSBP using
      bagasse pulp was examined under submerged (SmC) and solid-state cultivation
      (SSC). Higher level of xylanase activity (19,320 +/- 37 U g(-1) dried carbon
      source) was obtained in SSC cultures than in SmC (1,772 +/- 15 U g(-1) dried
      carbon source) after 120 h with 10% inoculum. The biobleaching efficacy of crude
      xylanase was tested on bagasse pulp, and the maximum brightness of 46.1 +/- 0.06%
      was observed with 50 U of crude xylanase per gram of pulp, which was 3.8 points
      higher than the brightness of untreated samples. Reducing sugars (26 +/- 0.1 mg
      g(-1)) and UV-absorbing lignin-derived compounds in the pulp filtrates were
      observed as maximum in 50 U of crude xylanase-treated samples. T. lanuginosus
      SSBP has potential applications due to its high productivity of xylanase and its
      efficiency in pulp bleaching.

PMID- 18802694
TI  - Cloning and functional characterization of a complex endo-beta-1,3-glucanase from
      Paenibacillus sp.
AB  - A beta-1,3-glucanase gene, encoding a protein of 1,793 amino acids, was cloned
      from a strain of Paenibacillus sp. in this study. This large protein, designated
      as LamA, consists of many putative functional units, which include, from N to C
      terminus, a leader peptide, three repeats of the S-layer homologous module, a
      catalytic module of glycoside hydrolase family 16, four repeats of the
      carbohydrate-binding module of family CBM_4_9, and an analogue of coagulation
      factor Fa5/8C. Several truncated proteins, composed of the catalytic module with
      various organizations of the appended modules, were successfully expressed and
      characterized in this study. Data indicated that the catalytic module
      specifically hydrolyze beta-1,3- and beta-1,3-1,4-glucans. Also, laminaritriose
      was the major product upon endolytic hydrolysis of laminarin. The CBM repeats and
      Fa5/8C analogue substantially enhanced the hydrolyzing activity of the catalytic
      module, particularly toward insoluble complex substrates, suggesting their
      modulating functions in the enzymatic activity of LamA. Carbohydrate-binding
      assay confirmed the binding capabilities of the CBM repeats and Fa5/8C analogue
      to beta-1,3-, beta-1,3-1,4-, and even beta-1,4-glucans. These appended modules
      also enhanced the inhibition effect of the catalytic module on the growth of
      Candida albicans and Rhizoctonia solani.

PMID- 18802695
TI  - Low representation of Fc receptor-like 1-5 molecules in leukemic cells from
      Iranian patients with acute lymphoblastic leukemia.
AB  - Recent studies have demonstrated expression of Fc receptor-like (FCRL) molecules,
      a newly identified family with preferential B-cell lineage expression, in some
      chronic B-cell leukemias with possible implication for classification and/or
      targeted immunotherapy. In this study, the expression pattern of FCRL1-5 genes
      was studied in 73 Iranian ALL patients and 35 normal subjects using semi
      quantitative RT-PCR method. FCRL protein expression was also investigated by flow
      cytometry. Our results indicate significant down-regulation of all FCRL genes in
      ALL compared to normal subjects. Although, FCRL mRNA expression was almost
      exclusively confined to normal isolated B-cells compared to T-cells, but these
      genes were similarly expressed in B-ALL, T-ALL and different B-ALL
      immunophenotypic subtypes. Surface protein expression of FCRL1, 2, 4, and 5
      molecules in 10 ALL and 5 normal samples confirmed the PCR results. Expression
      profile of FCRL molecules in different subtypes of ALL argues against their
      potential implication as suitable targets for classification and/or immunotherapy
      of ALL.

PMID- 18802696
TI  - Paclitaxel reduces regulatory T cell numbers and inhibitory function and enhances
      the anti-tumor effects of the TLR9 agonist PF-3512676 in the mouse.
AB  - The anti-tumor properties of Toll-like receptor (TLR) 9 agonist CpG
      oligodeoxynucleotides (ODN) are enhanced by combinations with several cytotoxic
      chemotherapy regimens. The mechanisms of this added benefit, however, remain
      unclear. We now report that, similar to the depletion of regulatory T cells
      (Treg) using anti-CD25, paclitaxel increased the anti-tumor effect of the TLR9
      agonist PF-3512676 in a CD8(+) T cell-dependent fashion. Paclitaxel treatment
      decreased Treg numbers in a TLR4-independent fashion, and preferentially affected
      cycling Treg expressing high levels of FoxP3. The paclitaxel-induced reduction in
      Treg FoxP3 expression was associated with reduced inhibitory function. Adoptively
      transferred tumor-antigen specific CD8(+) T cells proliferated better in mice
      treated with paclitaxel and their recruitment in the tumor was increased.
      However, the systemic frequency of PF-3512676-induced tumor-antigen specific
      effector CD8(+) T cells decreased with paclitaxel, suggesting opposite effects of
      paclitaxel on the anti-tumor response. Finally, gene expression profiling and
      studies of tumor-associated immune cells revealed a complex modulation of the PF
      3512676-induced immune response by paclitaxel, including a decrease of IL-10
      expression and an increase in IL-17-secreting CD4(+) T cells. Collectively, these
      data suggest that paclitaxel combined with PF-3512676 may not only promote a
      better anti-tumor CD8(+) response though increased recruitment in the tumor,
      possibly through Treg depletion and suppression, but also exerts more complex
      immune modulatory effects.

PMID- 18802697
TI  - High expression of PGE2 enzymatic pathways in cervical (pre)neoplastic lesions
      and functional consequences for antigen-presenting cells.
AB  - Although human papillomavirus (HPV) DNA is detected in the majority of squamous
      intraepithelial lesions (SIL) and carcinoma (SCC) of the uterine cervix, the
      persistence or progression of cervical lesions suggest that viral antigens are
      not adequately presented to the immune system. This hypothesis is reinforced by
      the observation that most SIL show quantitative and functional alterations of
      Langerhans cells (LC). The aim of this study was to determine whether
      prostaglandins (PG) may affect LC density in the cervical (pre)neoplastic
      epithelium. We first demonstrated that the epithelial expression of PGE(2)
      enzymatic pathways, including cyclooxygenase-2 (COX-2) and microsomal
      prostaglandin E synthase 1 (mPGES-1), is higher in SIL and SCC compared to the
      normal exocervical epithelium and inversely correlated to the density of CD1a
      positive LC. By using cell migration assays, we next showed that the motility of
      immature dendritic cells (DC) and DC partially differentiated in vitro in the
      presence of PGE(2) are differentially affected by PGE(2). Immature DC had a lower
      ability to migrate in the presence of PGE(2) compared to DC generated in vitro in
      the presence of PGE(2). Finally, we showed that PGE(2) induced a cytokine
      production profile and phenotypical features of tolerogenic DC, suggesting that
      the altered expression of PGE(2) enzymatic pathways may promote the cervical
      carcinogenesis by favouring (pre)cancer immunotolerance.

PMID- 18802699
TI  - Dermatomyositis associated with hepatitis B virus-related hepatocellular
      carcinoma.
AB  - Dermatomyositis (DM) is an idiopathic inflammatory myopathy (IIM) with typical
      cutaneous manifestations. It has been proposed that DM may be caused by
      autoimmune responses to viral infections, and previous studies have also shown
      that an association between DM and malignancy. However, chronic hepatitis B virus
      (HBV) infection associated with DM and hepatocellular carcinoma (HCC) is rarely
      encountered. The authors report a case of DM and HCC in a patient with a HBV
      infection. A 58-year-old man presented erythematous skin rashes on a sun-exposed
      area of 2 year's duration, and recent proximal muscle weakness. His medical
      history revealed that he had a chronic HBV infection. A diagnosis of DM relies on
      proximal muscle weakness, elevated muscle enzymes, myopathic changes
      (demonstrated by electromyography), muscle biopsy evidence of myositis, and its
      characteristic cutaneous findings. A Liver mass in the left lobe visualized by
      abdominal computed tomography was confirmed histologically as HCC. This case
      suggests that DM associated with HCC might be caused by a HBV infection.

PMID- 18802698
TI  - Drug resistance and genetic mapping in Plasmodium falciparum.
AB  - Drug resistance in malaria parasites is a serious public health burden, and
      resistance to most of the antimalarial drugs currently in use has been reported.
      A better understanding of the molecular mechanisms of drug resistance is urgently
      needed to slow or circumvent the spread of resistance, to allow local treatments
      to be deployed more effectively to prolong the life span of the current drugs,
      and to develop new drugs. Although mutations in genes determining resistance to
      drugs such as chloroquine and the antifolates have been identified, we still do
      not have a full understanding of the resistance mechanisms, and genes that
      contribute to resistance to many other drugs remain to be discovered. Genetic
      mapping is a powerful tool for the identification of mutations conferring drug
      resistance in malaria parasites because most drug-resistant phenotypes were
      selected within the past 60 years. High-throughput methods for genotyping large
      numbers of single nucleotide polymorphisms (SNPs) and microsatellites (MSs) are
      now available or are being developed, and genome-wide association studies for
      malaria traits will soon become a reality. Here we discuss strategies and issues
      related to mapping genes contributing to drug resistance in the human malaria
      parasite Plasmodium falciparum.

PMID- 18802700
TI  - Periodontal disease in rheumatoid arthritis and Sjogren's syndrome: a modifiable
      risk factor for atherosclerosis?

PMID- 18802701
TI  - The anti-Helicobacter pylori antibiotherapy for the treatment of recurrent oral
      aphthous ulcers in a patient with Behcet's syndrome.

PMID- 18802702
TI  - Association of (-1,607) 1G/2G polymorphism of matrix metalloproteinase-1 gene
      with knee osteoarthritis in the Turkish population (knee osteoarthritis and MMPs
      gene polymorphisms).
AB  - The aim of this study was to investigate whether functional polymorphisms in the
      promoter of matrix metalloproteinase-1 (MMP-1), MMP-2 and MMP-9 genes were
      associated with susceptibility to knee osteoarthritis in the Turkish population.
      The MMP-1 -1,607 1G/2G (rs1799750), MMP-2 -1,306 C/T (rs243865), and MMP-9 -1,562
      C/T (rs3918242) polymorphisms were determined by polymerase chain reaction
      restriction fragment length polymorphism assay in 157 patients diagnosed with
      knee osteoarthritis based on the criteria of American College of Rheumatology and
      in 84 controls in Mersin, Turkey. Genotype distributions and allele frequencies
      of MMP-1, MMP-2, and MMP-9 gene polymorphisms were compared between the patients
      and controls. There were significant differences between the groups regarding the
      genotype distribution of MMP-1 polymorphism (P = 0.001). The frequencies of 1G/1G
      and 1G/2G genotypes were significantly higher in the knee osteoarthritis than in
      the controls (P = 0.002, and P = 0.006, respectively). In addition, 1G allele
      frequency of MMP-1 gene was higher in the patients than in the control group (P =
      0.0001). The genotype distributions and allele frequencies of MMP-2 and MMP-9
      gene polymorphisms did not differ between the osteoarthritis and the control
      groups (P > 0.05). These findings suggest that the -1,607 1G/2G polymorphism in
      the MMP-1 gene may contribute to susceptibility to knee osteoarthritis in the
      Turkish population.

PMID- 18802703
TI  - Influence of humanized anti-IL-6R antibody, tocilizumab on the activity of
      soluble gp130, natural inhibitor of IL-6 signaling.
AB  - Tocilizumab, humanized anti-IL-6R antibody is a novel anti-rheumatic drug. In the
      present study, we examined the influence of tocilizumab on the inhibitory
      activity of soluble gp130 (sgp130) against IL-6 signaling. BAF-h130 cells, human
      gp130 transfected mouse pro-B cell line, were cultured with the mixture with IL
      6, sIL-6R and sgp130 for 72 h. BAF-h130 cells proliferated by the addition of
      both IL-6 and sIL-6R, but not IL-6 or sIL-6R alone. The proliferation induced by
      IL-6/sIL-6R complex was inhibited by sgp130 concentration-dependently.
      Tocilizumab inhibited IL-6/sIL-6R-induced cell proliferation. On the other hand,
      it did not affect the suppressive property of sgp130. To examine if tocilizumab
      can dissociate IL-6/sIL-6R/sgp130 complex, we established an ELISA system to
      detect IL-6/sIL-6R/sgp130 complex using anti-IL-6R coated ELISA plate. The
      results clearly indicated that ELISA system established was detectable IL-6/sIL
      6R/sgp130 complex in a concentration dependent manner. Tocilizumab was added to
      IL-6/sIL-6R/sgp130 complex-fixed plate and then remaining IL-6/sIL-6R/sgp130
      complexes on the plate were measured. The amount of IL-6/sIL-6R/sgp130 complexes
      on the plate was not changed by the addition of tocilizumab. In conclusion,
      tocilizumab exerts its inhibitory effect through the inhibition of IL-6R directly
      without affecting natural inhibitor sgp130.

PMID- 18802704
TI  - Clinical utility of cardiac magnetic resonance imaging in Churg-Strauss syndrome:
      case report and review of the literature.
AB  - We describe a case of an individual with Churg-Strauss syndrome who presented
      with a cerebrovascular accident (CVA) secondary to left ventricular intracavitary
      thrombi. Noninvasive cardiovascular imaging using transthoracic echocardiography
      (TTE) and cardiac magnetic resonance (CMR) was used to identify the cardioembolic
      source of CVA. The clinical utility of CMR in the management of patients with
      Churg-Strauss syndrome is reviewed.

PMID- 18802705
TI  - Targeting the CD134-CD134L interaction using anti-CD134 and/or rhCD134 fusion
      protein as a possible strategy to prevent lupus nephritis.
AB  - Lupus nephritis (LN) is characterized by an increased upregulation of Th1. This
      study was undertaken to evaluate the role of CD134 in cytokine production in
      peripheral blood mononuclear cells (PBMCs) from subjects with LN. Percentages of
      IFN-gamma- (Th1), IL-4-, and IL-10- (Th2) producing cells within the PBMC CD4+ T
      cell population of LN subjects were found to be higher than those of healthy
      subjects. Stimulation of PBMC from LN subjects with anti-CD3 epsilon mAb/rIL-2
      resulted in further increases in cytokine production. Stimulation in the presence
      of anti-CD134 mAb resulted in reduced IL-4 and IL-10 production; however, it also
      resulted in increased IFN-gamma production. Stimulation in the presence of the
      fusion protein rhCD134:Fc resulted in decreased production of all three
      cytokines. The possibilities that anti-CD134 therapy may control the extent of IL
      4- and IL-10-mediated damage in active LN and that rhCD134:Fc therapy may prevent
      occurrence of LN are discussed.

PMID- 18802706
TI  - Efficacy of tacrolimus in infliximab-refractory progressive rheumatoid arthritis.
AB  - We report a Japanese male patient with intractable rheumatoid arthritis (RA), in
      whom tacrolimus was effective ultimately. Five years before the admission he was
      diagnosed as RA, which was resistant to various disease-modifying anti-rheumatic
      drugs (DMARDs). Two years before, administration of infliximab was initiated
      although the medicine failed to control RA. In spite of the multiple joint
      replacement, the RA disease activity worsened. Tacrolimus (1.5 mg/day) was
      administered. Twenty-four weeks of tacrolimus treatment reduced the disease
      activity score for 28 joints-erythrocyte sedimentation rate from 7.44 to 3.65.
      Herein, we present a patient with RA, who was successfully treated by tacrolimus,
      and in whom infliximab was not effective. Tacrolimus may be one of the drugs for
      RA patients refractory to the conventional treatments including methotrexate or
      tumor necrosis factor inhibitors.

PMID- 18802707
TI  - Occludin expression in goldfish held in ion-poor water.
AB  - With an emphasis on the tight junction protein occludin, the response of goldfish
      following abrupt exposure (0-120 h) as well as long-term acclimation (14 and 28
      days) to ion-poor water (IPW) was examined. Both abrupt and long-term exposure to
      IPW lowered serum osmolality, [Na(+)] and [Cl(-)], and elevated serum glucose.
      After abrupt exposure to IPW, gill tissue exhibited a prompt and sustained
      decrease in Na(+)-K(+)-ATPase activity, and a transient increase in occludin
      expression that returned to control levels by 6 h. Following 14 and 28 days in
      IPW, gill occludin expression was markedly elevated, while Na(+)-K(+)-ATPase
      activity was only significantly different (elevated) at day 14. Kidney tissue
      exhibited an elevation in both Na(+)-K(+)-ATPase activity and occludin expression
      after 28 days; however, in the intestine, occludin expression declined at day 14
      but did not differ from FW fish at day 28. These studies demonstrate that
      goldfish can tolerate abrupt as well as sustained exposure to ion-poor
      surroundings. Data also suggests that occludin may play an adaptive role in
      fishes acclimated to ion-poor conditions by contributing to the modulation of
      epithelial barrier properties in ionoregulatory tissues.

PMID- 18802708
TI  - Measurements of burr-hole localization for endoscopic procedures in the third
      ventricle in children.
AB  - OBJECTIVE: In a retrospective study, we measured the localization for the burr
      hole for neuroendoscopic procedures in the third ventricle, which are determined
      by anatomical landmarks like the foramen of Monro (FM) and the respective
      targets. PATIENTS AND METHODS: In 48 children, thin-sliced T2-weighted magnetic
      resonance images were analyzed within an imaging software tool to determine the
      trajectory between the FM to the floor of the third ventricle (F3V) or the
      entrance of the sylvian aqueduct (SA). The crossing point at the skull convexity
      defined the entry points. Coordinates are given relative to nasion and midline. A
      mean virtual entry point to reach both targets was compared to the burr-hole
      localization used in the respective surgeries. The tissue shift at the FM was
      quantified for the trajectories. RESULTS: The entry point to reach the F3V or the
      SA measured 119.7+/-26.4 mm (to nasion)-20.5+/-11.5 mm (to midline) and 57.4+/
      26.5-18.8+/-8.3 mm, respectively. The virtual mean entry point to reach both
      targets was located at 86.5+/-25.3-20.9+/-9.8 mm. There was a statistical
      difference in the entry point localization relative to nasion of the virtual mean
      trajectory compared with the burr-hole localization used in these patients. The
      tissue shift at the level of the FM using the mean virtual trajectory was
      significantly lower than by using the actual burr hole to the SA. CONCLUSIONS:
      Planning an optimal burr-hole localization is important in neuroendoscopic
      procedures in children, especially where the target is located around the sylvian
      aqueduct.

PMID- 18802709
TI  - Cerebellar mutism after spontaneous intratumoral bleeding involving the upper
      cerebellar vermis: a contribution to the physiopathogenic interpretation.
AB  - BACKGROUND: Transient mutism as a consequence of posterior fossa surgery is a
      well-known phenomenon. However, it has rarely been reported after focal
      nonsurgically induced cerebellar damage. CASE REPORT: We describe a 7-year-old
      child affected by a tumor arising from the quadrigeminal plate who developed
      transient cerebellar mutism after a spontaneous bleeding which extended to the
      upper cerebellar vermis. The recovery from mutism started about a week after the
      bleeding. At the time of the surgical treatment, 8 weeks after the spontaneous
      intratumoral bleeding, she was only dysarthric. DISCUSSION: To our knowledge,
      this is the first pediatric case of presurgical cerebellar mutism due to a
      hemorrhage of a neoplastic lesion. Moreover, the focality of bleeding allows the
      confirmation of the role played by the upper vermis in speech control as well as
      exclusion of surgically induced lesions commonly suggested as possible cause of
      the cerebellar mutism.

PMID- 18802710
TI  - Neurofibromatosis type 1 and infantile spasms.
AB  - BACKGROUND: There is no agreement on the prevalence, natural history and outcome
      of infantile spasms (IS) in neurofibromatosis type 1 (NF1). By contrast, its
      prevalence and outcome are well characterised in the setting of other
      neurocutaneous disorders (e.g. tuberous sclerosis). MATERIALS AND METHODS: The
      aim of the present study was to try to establish a genotype-phenotype correlation
      in IS in the setting of NF1. A retrospective (years 1990-2000) and prospective
      (years 2000-2006) study in three paediatric centres in Italy were taken as
      referral populations for: (1) children with NF1 and (2) neurological problems in
      childhood. RESULTS: Ten NF1 patients have had IS. The calculated population
      based: (1) prevalence of IS in NF1 (0.76%) was higher than the reported frequency
      of IS in the general population (0.02-0.05%) and (2) frequency of NF1 in the IS
      series in two out of three centres (0.62-0.90%) was lower than the estimated
      frequencies in the literature (1.5-3.0%). Patients had psychomotor delay
      preceding the spasms (50%), symmetrical spasms (50%), typical (80%) and modified
      (20%) hypsarrhythmia and foci of spikes and waves and a good response to
      corticosteroid treatment (50%). Outcome was good in 30%. Imaging revealed high
      signal foci in atypical locations (sub-cortical and central brain regions).
      Deoxyribonucleic acid analysis revealed three novel NF1 gene mutations without
      genotype-phenotype correlation. CONCLUSION: Even though the combination of IS and
      NF1 does not seem to be coincidental, it is certainly an unusual event in NF1-
      rarer than in other neurocutaneous disorders. Spasms in NF1 are not associated
      with specific genetic defects.

PMID- 18802711
TI  - The clinical experience of medulloblastoma treatment and the significance of time
      sequence for development of leptomeningeal metastasis.
AB  - OBJECTS: Among patients with medulloblastoma, an unrare aggressive central
      nervous system (CNS) tumor found mostly in the posterior fossa, drop metastasis
      from primary location to anatomically lower sites including whole spinal cord is
      known as a potential way for tumor to spread. There were already lots of
      extensive discussions regarding diagnosis and treatment for such common
      neurologic complication in systemic cancer; however, fewer were found about
      medulloblastoma. This study aimed to reexamine the possible known prognostic
      factors, especially drop metastasis, and defined the influence of them. MATERIALS
      AND METHODS: We retrospectively review a series of 36 patients who suffered from
      posterior fossa medulloblastoma and found leptomeningeal metastasis in 12 of
      them. Incidence, diagnosis, prognostic factors, and treatments for this common
      complication are discussed. The magnetic resonance images (MRI) of these patients
      were reviewed. The time sequence between primary surgical procedure and
      development of MRI evidences of drop metastasis was used for subgrouping. Log
      rank test was used for survival analysis. CONCLUSIONS: By survival analysis,
      patients with late drop metastasis, defined as new radiologic evidence of
      leptomeningeal involvement after primary CNS procedures, were found to have
      significant survival difference to those with early metastasis defined as drop
      metastasis found at the time of diagnosis (log-rank test, p = 0.0047). Further
      stratification of patients within this group may help in evaluation of prognosis
      and development of different treatment strategies.

PMID- 18802712
TI  - Cementing technique in femoral resurfacing.
AB  - INTRODUCTION: The cementing technique is one of the various speculated factors
      that might contribute to the failures of resurfacing arthroplasty of the hip. The
      influence of bony preparation by jet lavage or lavage only in combination with
      different cementing techniques and cements of different viscosity in a study on
      fresh human femoral heads has not been evaluated so far. MATERIALS AND METHODS:
      Sixty fresh human femoral heads were prepared for resurfacing following
      manufacturers' instructions and divided into 12 groups. The different groups
      received either syringe lavage or jet lavage and either a low-, medium- or high
      viscosity cement with either packing or quarter filling of the implant with
      recess of the femoral stem in each case. Application of the implant was
      standardized. After polymerization, the femoral heads were cut into quarters and
      polished. Cement penetration was assessed using a square millimeter grid under
      optical zoom. RESULTS: Manual packing with high viscosity cement is a
      reproducible method in resurfacing arthroplasty. Syringe lavage and jet lavage
      mainly showed comparable cement penetration patterns when applied same cementing
      techniques. The penetration depth ranged from a mean of 0.6 to 3.2 mm with 0.4
      being the lowest and 4.0 being the deepest. The mantle thickness ranged from 0.8
      to 2.4 mm with statistically significant thicker mantles with filling, compared
      to packing. CONCLUSION: Our results showed distinct less penetration depth than
      previously reported and that just medium viscosity cement reached reliable
      results in the supposed range of penetration depth and cement mantle thickness.
      Jet lavage should be recommended for the low-viscosity cement but avoided in
      combination with a cement filling technique of lower viscosity cements. Filling
      of the implant caused the greatest penetration depth and a higher number of
      incomplete seatings and should therefore be avoided.

PMID- 18802713
TI  - Extension limitation and deviation of fingers by the scarred junctura tendinum: a
      case report.
AB  - The juncturae tendinum (inter-extensor connections) are structures connecting
      each of the extensor digitorum communis (EDC) tendons. Nine months before the
      presentation to us, this 21-year-old man had painful swelling on the dorsum of
      the right hand after punching. At present, the patient showed an ulnar deviation
      of the long finger and a limited extension of the ring finger. The scarred
      junctura tendinum between long and ring fingers inhibited proximal sliding of the
      EDC tendon of ring finger, and affect the functions of adjacent
      metacarpophalangeal joint. The scarred junctura tendinum was resected, while the
      sagittal band was preserved to prevent subluxation of the EDC tendon of long
      finger. One year after operation, the range of motion of fingers was full.

PMID- 18802714
TI  - Scarf versus proximal closing wedge osteotomy in hallux valgus treatment.
AB  - AIM: The aim of this study was to evaluate the distal metatarsal articular angle
      as a key factor in choosing between the proximal closing wedge osteotomy and
      scarf osteotomy. METHOD: The investigation involved 40 feet: 32 females aged 13
      68 in whom 24 unilateral and 8 bilateral operations had been performed from 24 to
      63 months previously. RESULTS: There were statistically significant differences
      between groups in the postoperative hallux valgus angle and in first metatarsal
      shortening. We found an inverse correlation between the preoperative distal
      metatarsal articular angle and intermetatarsal angle improvement after proximal
      closing wedge osteotomy and a positive correlation after scarf osteotomy.
      CONCLUSION: This study confirmed the value of distal metatarsal articular angle
      assessment.

PMID- 18802715
TI  - Cutaneous polyarteritis nodosa: revisiting its definition and diagnostic
      criteria.
AB  - Polyarteritis nodosa (PN) is a classical collagen disease with poor prognosis
      that demonstrates systemic necrotizing vasculitis of small and medium-sized
      arteries. Cutaneous symptoms are observed in 25-60% of PN patients. On other
      hand, cutaneous polyarteritis nodosa (CPN) is designated for the cutaneous
      limited form of PN and demonstrates benign prognosis. However, there has been
      much debate on whether or not CPN can progress to PN. Although CPN lesions are
      fundamentally limited to skin, some CPN cases show extracutaneous symptoms such
      as peripheral neuropathy and myalgia. According to PN diagnostic criteria, which
      were established by the Ministry of Health, Labour and Welfare of Japan, a
      disease with both cutaneous and at least one extracutaneous symptom with
      appropriate histopathological findings can be diagnosed as PN. The same is true
      according to diagnostic criteria established by the American College of
      Rheumatology. In addition, there are no specific diagnostic criteria for CPN. In
      this study, CPN cases were retrospectively collected from multiple Japanese
      clinics, and analyzed for detailed clinical and histopathological manifestations,
      in order to redefine the clinical entity of CPN and to propose appropriate
      diagnostic criteria for CPN and PN. According to the CPN description in Rook's
      Textbook of Dermatology, we collected 22 cases with appropriate histopathological
      findings. Of the 22 cases, none progressed to PN or death during the follow-up
      period, 32% had peripheral neuropathy and 27% had myalgia. Regarding
      extracutaneous symptoms with CPN, 17 dermatological specialists in vasculitis
      sustained the opinion that CPN can be accompanied by peripheral neuropathy and
      myalgia but these symptoms are limited to the same area as skin lesions. Based on
      these results, we devised new drafts for CPN and PN diagnostic criteria. Our
      study shows the efficacy of these criteria and most dermatologists recognized
      that our new diagnostic criteria for CPN and PN are appropriate at the present
      time. In conclusion, this study suggests that CPN does not progress to PN, and
      introduces new drafts for CPN and PN diagnostic criteria.

PMID- 18802716
TI  - Synchronous primary tumors of the female genital tract: a single center
      experience.
AB  - BACKGROUND: The present study aims to characterize the women diagnosed with
      synchronous primary gynecological tumors with an emphasis on risk factors.
      METHODS: A total of 21 patients were identified with synchronous primary
      gynecological tumors between 2000 and 2006. Demographic, clinical and pathologic
      data were obtained from medical records and pathology reports. RESULTS: The
      majority of the study population (52.4%) was diagnosed with independent primary
      endometrial and ovarian tumors. The most common presenting symptoms were pelvic
      pain and abnormal vaginal bleeding. Tobacco use was significantly more frequent
      in women with synchronous cervical-ovarian tumors. There was no statistically
      significant difference in exogenous hormone use among patients with different
      synchronous tumors. Diabetes mellitus and hypertension were significantly more
      frequent in women with endometrial-ovarian tumors. Although the women with
      synchronous cervical-ovarian tumors were significantly younger and leaner, they
      had shorter survival periods. CONCLUSION: Synchronous primary gynecologic tumors
      are usually detected in relatively older, overweight, multiparous and
      postmenopausal women with personal history of diabetes mellitus or hypertension.
      Synchronous primary tumors of endometrium and ovary are supposed to have better
      prognosis as they are diagnosed at early stage and low grade.

PMID- 18802717
TI  - The role of preoperative CT scan in patients with chronic otitis media.
AB  - Chronic otitis media may be due to chronic mucosal disease or cholesteatoma.
      Differentiating the two is usually achieved by clinical examination. The computed
      tomography (CT) scan is the standard imaging technique for the temporal bone, but
      its exact role in the preoperative assessment of patients with chronic otitis
      media is controversial. In this retrospective study we compared preoperative CT
      results with operative findings in 50 patients who had scan between January 2003
      and December 2007. We analyzed the clinical presentation and checked if CT scan
      confirmed or excluded the presence of cholesteatoma and if this was affected by
      previous surgery. We concluded that CT scan could not be relied on to
      differentiate cholesteatoma from chronic mucosal disease. It should be used
      selectively in the preoperative preparation only if complications of the disease
      suspected.

PMID- 18802718
TI  - Effects of buffered 2.3%, buffered 0.9%, and non-buffered 0.9% irrigation
      solutions on nasal mucosa after septoplasty.
AB  - A prospective randomized study was designed to compare the effect of different
      irrigation solutions on mucociliary clearance and nasal patency and to compare
      the limitations of the used solutions, such as nasal burning by a visual analog
      scale. Forty-five patients who underwent septoplasty were divided into three
      groups postoperatively. Each group was administered with 2.3% buffered hypertonic
      seawater, buffered isotonic saline solution and non-buffered isotonic saline,
      respectively, as irrigation fluid. Saccharine test and acoustic rhinometer were
      used to determine mucociliary activity and nasal patency. Patients were asked
      about the burning sensation using a 10-cm visual analog scale. There was no
      significant difference in saccharine clearance time (SCT) on the 5th
      postoperative day between the three groups (P = 0.07). On the 20th day, there was
      a significant difference in SCT between the hypertonic buffered seawater group
      and non-buffered isotonic saline (P = 0.003). Buffered hypertonic seawater
      improved nasal airway patency more than the buffered isotonic saline (P = 0.004).
      Buffered hypertonic solutions used after endonasal surgery have been advantageous
      for both mucociliary clearance and postoperative decongestion.

PMID- 18802719
TI  - Fundus autofluorescence in serpiginous choroiditis.
AB  - BACKGROUND: Fundus autofluorescence is already used to evaluate inflammatory
      disorders affecting the chorioretinal interface. We investigated the
      autofluorescence characteristics of two cases of serpiginous choroiditis (SC)
      during recurrent acute episodes, and followed them until their resolution. We
      compared the autofluorescence findings with those obtained with other imaging
      techniques. METHODS: Autofluorescence photographs of the eyes were taken in a 26
      year-old female and a 68-year-old male with SC at the first appearance of active
      lesions and during a strict follow-up period. Patients had complete
      ophthalmological evaluations including optical coherence tomography (OCT) and
      fluorescein and indocyanine green (ICG) angiography. Autofluorescence findings
      were compared with features from other imaging techniques. Patients were treated
      with systemic or intravitreal steroids. RESULTS: Hyperautofluorescence was
      detected 2 to 5 days after the appearance of the lesions, providing a clear
      delineation of the area of definitive retinal pigment epithelium (RPE) damage.
      This area was less extensive than the perfusion defect of the choriocapillaris
      indicated by ICG angiography. OCT showed very early increased reflectance of the
      photoreceptor layer in the area of hyperautofluorescence. A progressive decrease
      in autofluorescence was seen during the scarring phase of the disease. OCT
      changes in the photoreceptor layer were still present in the atrophic
      hypoautofluorescent lesions. CONCLUSION: Fundus autofluorescence seems to be a
      very sensitive imaging technique for detecting damage of the RPE in acute
      episodes of SC. A sequence of autofluorescence changes reflects the passage from
      activation to resolution of new lesions. Similarities, but also differences can
      be found by comparing our SC findings with those obtained with autofluorescence
      and OCT in posterior multifocal placoid pigment epitheliopathy.

PMID- 18802720
TI  - Prevalence and determinants of non-adherence to topical hypotensive treatment in
      Dutch glaucoma patients.
AB  - BACKGROUND: To assess the prevalence and determinants of non-adherence to topical
      hypotensive treatment in glaucoma patients in order to support interventions
      targeting enhancement of patient adherence. METHODS: One-hundred and sixty-six
      glaucoma patients, recruited by nationwide multi-stage sampling, filled in an
      extensive and carefully developed questionnaire covering various theoretically
      relevant determinants of patient adherence which were categorized as psychosocial
      aspects, barriers and skills. RESULTS: Prevalence of self-reported non-adherence
      was 27.3%. Younger patients (<55 years of age) had a higher risk of being non
      adherent. Forgetfulness, unavailability of eye drops and difficulties with
      holding the bottle above the eye when applying the eye drops were the most cited
      reasons for non-adherence. Fifty percent of the patients indicated that they
      required more information on the correct administration of eye drops. There was
      no association between non-adherence and sex, level of education, type of
      insurance, duration of disease or family history of glaucoma. CONCLUSIONS: Non
      adherence to topical glaucoma medication is fairly common. Aids that minimize
      forgetfulness and delivery systems facilitating the delivery of medications to
      the eye could be considered to enhance patient adherence before advancing to
      other therapies with additional risks and costs.

PMID- 18802722
TI  - Gallbladder wall thickening in a patient with acute poststrepotcoccal
      glomerulonephritis.
AB  - Although thickening of the gallbladder wall is a relatively frequent finding on
      diagnostic imaging studies, the condition has never been reported in patients
      with acute poststreptococcal glomerulonephritis (APSGN). We describe a patient
      with APSGN who presented with transient thickening of the gallbladder wall. While
      the precise pathogenic mechanism underlying this change in our patient was
      unclear, elevated systemic venous pressure or subclinical vasculitis may have
      caused edema of the gallbladder wall.

PMID- 18802721
TI  - KRAS mutation testing for predicting response to anti-EGFR therapy for colorectal
      carcinoma: proposal for an European quality assurance program.
AB  - Novel therapeutic agents targeting the epidermal growth factor receptor (EGFR)
      have improved outcomes for patients with colorectal carcinoma. However, these
      therapies are effective only in a subset of patients. Activating mutations in the
      KRAS gene are found in 30-40% of colorectal tumors and are associated with poor
      response to anti-EGFR therapies. Thus, KRAS mutation status can predict which
      patient may or may not benefit from anti-EGFR therapy. Although many diagnostic
      tools have been developed for KRAS mutation analysis, validated methods and
      standardized testing procedures are lacking. This poses a challenge for the
      optimal use of anti-EGFR therapies in the management of colorectal carcinoma.
      Here we review the molecular basis of EGFR-targeted therapies and the resistance
      to treatment conferred by KRAS mutations. We also present guideline
      recommendations and a proposal for a European quality assurance program to help
      ensure accuracy and proficiency in KRAS mutation testing across the European
      Union.

PMID- 18802723
TI  - 'Light-chain escape-multiple myeloma'-an escape phenomenon from plateau phase:
      report of the largest patient series using LC-monitoring.
AB  - PURPOSE: More intensive and novel therapy options in multiple myeloma (MM) hold
      the promise to improve treatment outcome. However, disease evolution, induced
      with long disease duration and extensive pretreatment, has resulted in changes in
      the biological behaviour of MM and unusual relapse emergence, such as of
      extramedullary (EM) disease or a shift in secretion from intact immunoglobulin
      (Ig) to free-light chains (FLCs) only. METHODS: We studied ten patients since
      2004, thoroughly assessed relevant patient characteristics, prominent
      similarities, SFLC-changes, therapy response, mode and speed of progression, and
      the incidence of light-chain escape (LCE)-MM within our entire myeloma patient
      cohort. Serum FLCs (SFLCs) were determined via Freelite-assay (Dade-Behringer
      Nephelometer). RESULTS: This report summarizes the to date largest series of ten
      patients, whose MM appeared stable, as judged by conventional monitoring of
      intact Ig levels, but developed severe organ dysfunction as a consequence of
      initially undetected LC-progression. Median number of anti-MM cycles before LCE
      occurrence was six, including autologous and/or allogeneic stem cell transplants
      and novel drugs, predominantly thalidomide, in 4/10. Classic diagnostics, such as
      electrophoresis and quantitative Ig measurement proved futile to detect LC
      progression, whereas SFLCs were reliable markers. The LCE-MM prevalence within
      407 MM patients treated in our institution between 2004 and 2007 was 2.46%.
      CONCLUSIONS: Our report suggests that early detection of LCE-MM by means of
      serial SFLC measurements may prevent unnecessary complications, allows to detect
      unusual relapse manifestations in the era of intensive and biological therapy
      options and possibly also permits to improve treatment results in LCE-MM.

PMID- 18802724
TI  - An immunocytochemical, histochemical and ultrastructural study of the nervous
      system of the tapeworm Cyathocephalus truncatus (Cestoda, Spathebothriidea).
AB  - This study is the first detailed study of the organisation of the neuromuscular
      system of Cyathocephalus truncatus (Cestoda, Spathebothriidea). Five techniques
      have been used: (1) immunocytochemistry, (2) staining with TRITC-conjugated
      phalloidin, (3) NADPHdiaphorase histochemistry, (4) confocal scanning laser
      microscopy and (5) transmission electron microscopy. The patterns of nerves
      immunoreactive (IR) to antibodies towards serotonin (5-HT) and the invertebrate
      neuropeptide FMRFamide are described in relation to the musculature. The patterns
      of NADPHdiaphorase positive nerves and 5-HT-IR nerves are compared. The fine
      structure of the nervous system (NS) is described. The organisation of NS in the
      non-segmented, polyzoic C. truncatus differs clearly from that in the non
      segmented, monozoic Caryophyllaeus laticeps and shows distinct similarities with
      the NS in pseudophyllidean cestodes. This supports the hypothesis that taxon
      Caryophyllidea and Spatheobothriidea form independent lineages within Eucestoda.

PMID- 18802725
TI  - Regulation of expression of Sertoli cell glucose transporters 1 and 3 by FSH, IL1
      beta, and bFGF at two different time-points in pubertal development.
AB  - Sertoli cells are necessary to provide adequate levels of lactate for germ cell
      development. Lactate production is hormonally regulated by follicle-stimulating
      hormone (FSH) and by a large set of intratesticular regulators such as
      interleukin-1 beta (IL1 beta) and basic fibroblast growth factor (bFGF). Little
      is known regarding the critical step in the production of this metabolite, viz.,
      the entrance of glucose into the cell as mediated by GLUTs. The aim of the
      present study was to investigate the expression of the glucose transporters GLUT1
      and GLUT3 and its possible regulation by FSH, IL1 beta, and bFGF in Sertoli cells
      at two different time-points in sexual development. Sertoli cells retaining the
      ability to undergo mitosis (obtained from 8-day-old rats) and in the process of
      terminal differentiation (obtained from 20-day-old rats) were examined.
      Testicular tissue sections and Sertoli cell monolayers obtained from 8- and 20
      day-old rats showed positive immunostaining for GLUT1 and GLUT3 proteins. GLUT1
      and GLUT3 mRNA levels were detected at the two ages analyzed. Treatment of
      Sertoli cells obtained from 8- and 20-day-old rats with FSH, IL1 beta, and bFGF
      for various periods of time (12, 24, and 48 h) increased GLUT1 without changing
      GLUT3 mRNA levels. Our results thus show that Sertoli cells express GLUT1 and
      GLUT3 throughout pubertal development, and that, in Sertoli cells, only GLUT1 is
      regulated by hormones during pubertal development. Hormonal regulation of GLUT1
      expression and consequently glucose uptake and lactate production may be a key
      molecular event in the regulation of spermatogenesis by hormones.

PMID- 18802726
TI  - Clostridium difficile-associated disease in children with solid tumors.
AB  - GOALS OF WORK: The goal of this study was to describe the incidence of
      Clostridium difficile-associated disease (CDAD) in children with solid tumours.
      PATIENTS AND METHODS: After documentation of a case of C. difficile-associated
      pseudomembranous colitis in a patient with neuroblastoma, the presence of C.
      difficile toxins A and B was prospectively tested in all children undergoing
      antineoplastic chemotherapy for solid tumours or lymphomas at the "G. Gaslini"
      Children Hospital in Genoa who presented abdominal pain. MAIN RESULTS: From
      January 2005 to December 2006, nine (6%) out of 141 patients treated for solid
      tumours had C. difficile toxin A detected in their stools in the presence of
      abdominal symptoms including vomit, abdominal pain and diarrhoea. The majority of
      patients had a normal neutrophil count at onset of gastrointestinal disease No
      patient developed pseudomembranous colitis, and none died. All patients received
      antibiotics and/or antineoplastic drugs previously associated with CDAD.
      CONCLUSIONS: CDAD may be a complication of children with solid tumours. Since
      this disease may be life threatening and cause epidemic clusters, this
      possibility must be kept in mind for the differential diagnosis of abdominal
      diseases in children with cancer, especially in absence of neutropenia.

PMID- 18802727
TI  - Decision making and quality of life in the treatment of cancer: a review.
AB  - INTRODUCTION: Complexity in decision making for cancer treatment arises from many
      factors. When considering how to treat patients, physicians prioritize factors
      such as stage of disease, patient age, and comorbid illnesses. However,
      physicians must balance these priorities with the patient's preferences, quality
      of life, social responsibilities, and fear of uncertainty. Although these factors
      are important, physicians are often unable to effectively judge their patients'
      preferences. Patients are often unable to fully understand their prognoses and
      the treatment intent. DISCUSSION: These differences influence how patients and
      physicians make treatment-related decisions. Partially due to these differences,
      patients are initially more likely than their physicians to accept greater risk
      for lesser benefit from treatment. As time progresses and as they experience
      treatment, a patient's preference changes, yet little is known about this process
      since few studies have examined it in a prospective longitudinal manner. We
      present an overview of the literature related to patient and physician decision
      making and quality of life in patients with advanced cancer, and we propose
      approaches to future decision-making models in cancer treatment.

PMID- 18802728
TI  - In vitro activity of tigecycline against multidrug-resistant Enterobacteriaceae
      isolates from a Belgian hospital.
AB  - Bacterial resistance among Gram-negative pathogens is a challenging clinical
      problem. Tigecycline has been developed specifically to overcome resistance. The
      aim of this study was to assess the in vitro activity of tigecycline against ESBL
      producing Escherichia coli, ESBL-producing Klebsiella spp., and multidrug
      resistant Enterobacter spp. Between May 2007 and March 2008, 26 strains of ESBL
      producing Escherichia coli, 10 strains of ESBL-producing Klebsiella spp., and 27
      strains of multidrug-resistant Enterobacter spp. were isolated consecutively from
      inpatients with a documented infection in which the collected isolate was
      identified as the probable causative organism. The in vitro susceptibility
      against tigecycline was measured by the E-test method. MIC(50) values were 1
      microg/ml, 2 microg/ml, and 3 microg/ml respectively. MIC(90) values were
      respectively 1.5 microg/ml, 4 microg/ml, and 12 microg/ml. Nonsusceptibility
      rates of 35%, 100%, and 96% respectively were found using EUCAST breakpoints.
      Despite the limited number of strains tested, our in vitro data suggest that
      tigecycline is unsuitable for the treatment of infections with multidrug
      resistant Enterobacteriaceae in our setting. Therefore, we suggest that larger
      multicenter studies should be conducted to reconsider the value of tigecycline
      for the treatment of infections with multidrug-resistant, Gram-negative bacteria.

PMID- 18802729
TI  - Post-consumer use efficacies of preservatives in personal care and topical drug
      products: relationship to preservative category.
AB  - Ninety-six used personal care and topical OTC drug items collected from consumers
      in the USA were examined for the presence of microbial contaminants. Of the eye
      and face product type containing global preservative chemistries (i.e.,
      acceptable for use in Japan without major restrictions), 55% yielded numbers of
      microorganisms in excess of 500 CFU/g (P < 0.1814). For the mascara products with
      global preservative chemistries, 79% yielded numbers of microorganisms in excess
      of 500 CFU/g (P < 0.024). Products containing global preservative chemistries
      accounted for 88% (n = 14) of the products that had microbial contents above
      10(4) CFU/g (P < 0.001). Prominent contaminants were species of Staphylococcus,
      Pseudomonas, Klebsiella, Streptococcus, Lactobacillus, Bacillus, Corynebacterium,
      and yeast. In general, under the stress of consumer use, products preserved with
      global preservative chemistries did not maintain as adequate preservation as
      products with non-global preservatives.

PMID- 18802730
TI  - Sub-pixel localisation of passive micro-coil fiducial markers in interventional
      MRI.
AB  - OBJECTIVE: Electromechanical devices enable increased accuracy in surgical
      procedures, and the recent development of MRI-compatible mechatronics permits the
      use of MRI for real-time image guidance. Integrated imaging of resonant micro
      coil fiducials provides an accurate method of tracking devices in a scanner with
      increased flexibility compared to gradient tracking. Here we report on the
      ability of ten different image-processing algorithms to track micro-coil
      fiducials with sub-pixel accuracy. MATERIALS AND METHODS: Five algorithms:
      maximum pixel, barycentric weighting, linear interpolation, quadratic fitting and
      Gaussian fitting were applied both directly to the pixel intensity matrix and to
      the cross-correlation matrix obtained by 2D convolution with a reference image.
      RESULTS: Using images of a 3 mm fiducial marker and a pixel size of 1.1 mm,
      intensity linear interpolation, which calculates the position of the fiducial
      centre by interpolating the pixel data to find the fiducial edges, was found to
      give the best performance for minimal computing power; a maximum error of 0.22 mm
      was observed in fiducial localisation for displacements up to 40 mm. The inherent
      standard deviation of fiducial localisation was 0.04 mm. CONCLUSION: This work
      enables greater accuracy to be achieved in passive fiducial tracking.

PMID- 18802731
TI  - Use of finite element analysis in presurgical planning: treatment of mandibular
      fractures.
AB  - BACKGROUND: The current clinical procedure for mandible fracture fixation is
      plate application. 3D reconstructions are used to validate procedures numerically
      preceding experimental analysis. This study outlines the methods used to
      reconstruct a numerical model of the mandible. METHODS: A CT scan from a 22-year
      old male patient with a healthy unfractured mandible was obtained. A 3D
      reconstruction was carried out using Mimics via thresholding and segmentation
      techniques. Boundary conditions and muscle forces were applied, and simulations
      were performed using ABAQUS. RESULTS: 3D reconstruction allows for precise
      anatomical dimensions, which can be used for further engineering analysis. Using
      the surgical Champy technique as an example, results showed that the mandible
      model returned to normal function post-plating. CONCLUSIONS: The study shows the
      clinical relevance of 3D reconstructions to plan surgical procedures. Results
      illustrate the benefit of carrying out numerical validations as a prerequisite to
      experimental modelling and as a method of pre-validating surgical procedures.

PMID- 18802732
TI  - Minimum flows and levels method of the St. Johns River Water Management District,
      Florida, USA.
AB  - The St. Johns River Water Management District (SJRWMD) has developed a minimum
      flows and levels (MFLs) method that has been applied to rivers, lakes, wetlands,
      and springs. The method is primarily focused on ecological protection to ensure
      systems meet or exceed minimum eco-hydrologic requirements. MFLs are not
      calculated from past hydrology. Information from elevation transects is typically
      used to determine MFLs. Multiple MFLs define a minimum hydrologic regime to
      ensure that high, intermediate, and low hydrologic conditions are protected. MFLs
      are often expressed as statistics of long-term hydrology incorporating magnitude
      (flow and/or level), duration (days), and return interval (years). Timing and
      rates of change, the two other critical hydrologic components, should be
      sufficiently natural. The method is an event-based, non-equilibrium approach. The
      method is used in a regulatory water management framework to ensure that surface
      and groundwater withdrawals do not cause significant harm to the water resources
      and ecology of the above referenced system types. MFLs are implemented with
      hydrologic water budget models that simulate long-term system hydrology. The
      method enables a priori hydrologic assessments that include the cumulative
      effects of water withdrawals. Additionally, the method can be used to evaluate
      management options for systems that may be over-allocated or for eco-hydrologic
      restoration projects. The method can be used outside of the SJRWMD. However, the
      goals, criteria, and indicators of protection used to establish MFLs are system
      dependent. Development of regionally important criteria and indicators of
      protection may be required prior to use elsewhere.

PMID- 18802733
TI  - Results of a multimodal therapy in patients with stage IV Barrett's
      adenocarcinoma.
AB  - BACKGROUND: Locally advanced and metastatic Barrett's carcinomas account for the
      majority of this tumor entity at the time of diagnosis. Many studies have shown
      that a multimodal therapy concept consisting of neoadjuvant chemotherapy followed
      by resection can result in improved long-term survival in patients responding to
      chemotherapy. The benefit of a multimodal therapy concept in patients with stage
      IV disease remains unclear. METHODS: A total of 178 patients with Barrett's
      carcinoma who underwent multimodal therapy with resection of the tumor were
      reviewed. The pathological staging and the clinical course of patients with
      metastatic disease, who were treated equally, were compared to patients with
      locally advanced tumors. RESULTS: As expected, postoperative pathological staging
      showed that patients with metastatic disease have a more advanced T- and N
      status. Moreover, the histopathological response according to Becker showed a
      chemoresistence in 84% of cases with metastatic disease, whereas 54% of patients
      with locally advanced carcinomas had a good response rate. Overall survival was
      poor, with 9 months in the metastatic group. CONCLUSIONS: This is the first study
      to compare the outcome of a modern multimodal therapy concept in patients with
      metastatic Barrett's carcinoma in comparison to patients with the locally
      advanced form of the disease. There are profound differences in the two groups
      with regard to survival time and response rates. Because of the poor outcome to
      date, multimodal therapy with resection of the tumor in stage IV disease cannot
      be recommended.

PMID- 18802734
TI  - Additional mechanical pleurodesis after thoracoscopic wedge resection and
      covering procedure for primary spontaneous pneumothorax.
AB  - BACKGROUND: Additional mechanical pleurodesis for the treatment of primary
      spontaneous pneumothorax (PSP) is believed to reduce the recurrence of PSP, and a
      covering procedure with absorbable mesh also shows comparable results. This study
      was conducted to determine whether additional mechanical pleurodesis would be
      effective in reducing recurrence after thoracoscopic wedge resection and covering
      procedure. MATERIALS AND METHODS: Between May 2003 and August 2005, 99 patients
      underwent thoracoscopic bullectomy with staple line covering with absorbable
      cellulose mesh and fibrin glue followed by an additional mechanical pleurodesis.
      These patients were compared with 98 patients who underwent thoracoscopic
      bullectomy with staple line coverage alone. RESULTS: The additional mechanical
      pleurodesis group had findings comparable to those of the coverage group for
      duration of postoperative chest drainage, length of hospital stay, and
      complication rate. After median follow-up of 29.2 months, postoperative
      recurrence occurred in four patients (4.0%). CONCLUSIONS: Additional mechanical
      pleurodesis after covering procedure is also effective in decreasing
      postoperative recurrence of PSP.

PMID- 18802735
TI  - Laparoscopic rectal cancer surgery with and without neoadjuvant chemo
      irradiation: a comparative study.
AB  - OBJECTIVES: To evaluate the perioperative short-term outcomes of laparoscopic
      rectal cancer surgery in patients after neoadjuvant chemo-irradiation. PATIENTS
      AND METHODS: This is a comparative cohort study designed to compare the
      perioperative and short-term outcomes of laparoscopic rectal cancer surgery in
      patients with and without neoadjuvant therapy. Patients undergoing elective
      laparoscopic rectal cancer surgery after neoadjuvant chemo-irradiation formed the
      study group; those receiving surgery without neoadjuvant therapy and in whom the
      final histology confirmed either transmural or node-positive diseases were
      selected as controls. RESULTS: Fifty-two patients in the neoadjuvant group were
      compared with 138 patients in the control group. Both groups were comparable in
      terms of American Society of Anesthesiologists (ASA) grading and gender
      distribution. Median operating time was significantly longer in the neoadjuvant
      group (155 versus 135 mins, p = 0.09, Mann-Whitney U test). No significant
      difference was observed in terms of blood loss, conversion rates, postoperative
      morbidity, length of hospital stay or sphincter preservation rates. Overall 5
      year survival rates in the two groups remained similar. CONCLUSIONS: Our data
      confirmed that, aside from a slightly longer operating time, laparoscopic rectal
      cancer surgery in patients with neoadjuvant chemo-irradiation is safe with no
      increased morbidity. Based on our experience, patients after neoadjuvant therapy
      should not be deterred from the minimally invasive approach.

PMID- 18802736
TI  - Results of a multicenter study of 1,057 cases of rectal cancer treated by
      laparoscopic surgery.
AB  - BACKGROUND: The aim of this study was to clarify the feasibility of laparoscopic
      surgery for rectal cancer retrospectively in 28 centers throughout Japan.
      METHODS: Between May 1994 and February 2006, 1,057 selected patients with rectal
      cancer underwent laparoscopic surgery. All the data regarding the patient
      details, and operative and postoperative outcome were collected retrospectively.
      RESULTS: Mean follow-up was 30 months. Procedures included anterior resection in
      938, abdominoperineal resection in 107, Hartmann's procedure in 10, and others in
      two patients. Conversion to open procedures occurred in 77 patients (7.3%).
      Postoperative surgical complications developed in 235 patients (22.2%), including
      anastomotic leakage in 84 (9.1%). Median length of postoperative hospital stay
      was 15 days (7-271 days). Patients with upper rectal cancer had shorter hospital
      stay than those with lower rectal cancer (14 versus 18 days, p < 0.01). Tumor
      node-metastases (TNM) stage included 83(7.9%) stage 0, 495 (46.8%) stage I, 197
      (18.6%) stage II, 230 (21.8%) stage III, and 52 (4.9%) stage IV. Recurrence was
      developed in 67 patients (6.6%) of the 1,011 curatively treated patients. Local
      recurrence occurred in 11 patients (1.0%). There was no port-site metastasis. Of
      the 1,011 curatively treated patients, the 3-year disease-free survival rate was
      100% in stage 0, 94.6% in stage I, 82.1% in stage II, and 79.7% in stage III.
      CONCLUSIONS: Laparoscopic surgery is feasible and safe in selected patients with
      rectal cancer, with favorable short-term and mid-term outcome.

PMID- 18802737
TI  - A new and standardized approach for trocar placement in laparoscopic Roux-en-Y
      gastric bypass.
AB  - INTRODUCTION: Super-morbidly obese patients undergoing laparoscopic Roux-en-Y
      gastric bypass (LRYGB) present unique technical challenges. In our experience the
      ease of the operation and the operative time seem to be more dependent on body
      habitus than body mass index (BMI). We hypothesized that the distance between the
      xyphoid process and the umbilicus (the XU distance) correlated with surgical
      difficulty and described an original modification of trocar placement based on
      this measurement to improve the ease of the operation. METHODS: Seven hundred and
      seventy-four patients underwent LRYGB, and the XU distance was measured in a
      subset of 38 patients midway through the experience. The need for additional
      trocars was assessed intraoperatively and the relationship between the XU
      distance and the need for extra trocars was subsequently analyzed. A standardized
      approach for trocar placement was implemented in the second half of our series.
      The operative time was compared between the standardized and nonstandardized
      groups. RESULTS: Fifty percent of the patients required a five-trocar technique.
      Median XU distance in this group was 21.4 cm (range 17-25 cm). In the remaining
      19 patients additional trocars were added; median XU distance was 27.3 cm (range
      24-33 cm). From the 774 patients included in the study period, the operative time
      for the first 322 patients who were completed with a nonstandardized trocar
      approach was significantly longer than the subsequent 452 cases in which the
      standardized trocar approach was used (210 versus 173 min, p < 0.001).
      CONCLUSIONS: We define XU distance as the key element in determining the choice
      of trocar placement. When XU distance is less then 25 cm, the basic approach
      should be used and if it is greater than 25 cm, the advanced trocar approach is
      recommended. This standardized technique leads to decreased operative time and
      improved ease of operation.

PMID- 18802738
TI  - Bioactive recombinant human lactoferrin, derived from rice, stimulates mammalian
      cell growth.
AB  - Today there is a concern about the use of animal source proteins and peptides in
      cell culture applications due to potential contamination by adventitious
      infectious pathogens. Recombinant production of these proteins using a plant host
      provides a safe and cost effective alternative. In this paper, we tested the
      effect of rice-derived recombinant human lactoferrin (rhLF) on mammalian cell
      growth. The purified rhLF was partially (about 50%) iron-saturated (pis-rhLF).
      Chemical modification of pis-rhLF generated apo-rhLF (<10% iron saturation) or
      holo-rhLF (>90% iron saturation). All three forms of rhLF (pis, apo, holo)
      promoted growth of intestinal cells (HT-29) measured as [(3)H]-thymidine
      incorporation or viable cell count, but holo-rhLF was most effective. Holo-rhLF
      was further tested on hybridoma, osteoblast, and human embryonic kidney cells.
      Results showed that holo-rhLF promoted cell growth and reduced cell doubling
      time. The concentration of holo-rhLF in media was critical in promoting cell
      growth and each cell line had different concentration dependence with the most
      effective range from 5 to 200 mg/L. The effect of rhLF on antibody production was
      determined using a hybridoma cell line. Significantly, more antibodies were
      produced by cells grown with holo-rhLF than cells grown without holo-rhLF. We
      also compared the effect of holo-rhLF to that of human transferrin, a component
      commonly used in cell culture media as an iron source. Holo-rhLF was as effective
      as human transferrin in promoting cell growth and antibody production.
      Considering all the data obtained, we conclude that rhLF from rice is effective
      in promoting mammalian cell growth and increasing cell productivity.

PMID- 18802739
TI  - Growth hormone pathway gene expression varies in porcine cumulus-oocyte complexes
      during in vitro maturation.
AB  - Growth hormone (GH) plays important roles in oocyte development and facilitates
      the successful production of competent oocytes in many species both in vivo and
      in vitro. However, the mechanism of GH action on oocyte maturation is not well
      known. In this paper, the temporospatial messenger ribonucleic acid expression
      patterns of GH and several other GH-related factors were quantitatively analyzed
      in porcine cumulus-oocytes complex throughout in vitro maturation (IVM). GH
      expression was decreased in oocytes during IVM while absent in cumulus cells. GH
      receptor, insulin-like growth factor-1 (IGF-1), and IGF-1 receptor expressions
      were also downregulated in oocytes. In cumulus cells, the expression of IGF-1
      decreased significantly while IGF-1 receptor expression remained constant. The
      transcripts of Janus kinase 2 increased in both oocytes and cumulus cells during
      IVM. The current precise gene expression information provides further evidence to
      explain the complex network of GH signaling involved in IVM of porcine oocyte.

PMID- 18802740
TI  - Adjustment to trauma exposure in refugee, displaced, and non-displaced Bosnian
      women.
AB  - The war in Bosnia resulted in the displacement of millions of civilians, most of
      them women. Ten years after the civil war, many of them are still living as
      refugees in their country of origin or abroad. Research on different refugee
      groups has continuously reported persistent levels of posttraumatic stress
      disorder (PTSD) and other mental-health problems in this population. The present
      study compared PTSD and self-concept in Bosnian refugee women (n = 29) with women
      who were internally displaced (IDP; n = 26) and non-displaced women (n = 32).
      Data were collected using the Bosnian Trauma Questionnaire and four scales
      assessing self-esteem, perceived incompetence, externality of control
      attribution, and persistence. IDPs scored significantly higher on PTSD symptoms,
      externality of control attribution and perceived incompetence, and lower on self
      esteem than both refugee and non-displaced women. The level of education most
      strongly predicted PTSD symptom severity, followed by the type of displacement,
      and exposure to violence during the war. Associations of self-concept with
      displacement and psychopathology were inconsistent, with type of displacement
      predicting control attributions but not other aspects of self-concept and PTSD
      symptoms being partly related to perceived incompetence and self-esteem. These
      results support previous findings stating that, in the long run, refugees show
      better mental health than IDPs, and that witnessing violence is a traumatic
      experience strongly linked to the development of PTSD symptoms. Results further
      indicate that education plays an important role in the development of PTSD
      symptoms. Associations of control attributions and type of displacement were
      found; these results have not been previously documented in literature.

PMID- 18802741
TI  - Inflammatory cytokine modulation of matrix metalloproteinase expression and
      invasiveness of glioma cells in a 3-dimensional collagen matrix.
AB  - Glioma invasiveness is accomplished in part by matrix metalloproteinases (MMPs)
      which remodel the constraints of the three dimensional (3D) matrix of the brain
      parenchyma. Tissue culture studies have advanced knowledge of glioma invasiveness
      but the majority of studies have used a two dimensional (2D) monolayer culture
      system which does not reproduce the spatial constraints of invasiveness in vivo.
      Here, we have used a 3D matrix of type I collagen (CL) gel to address glioma
      invasiveness in vitro. We show that in 3D CL matrix, interleukin-1 beta (IL
      1beta) and tumor necrosis factor-alpha (TNF-alpha), cytokines which are elevated
      in gliomas in vivo, increased glioma cell invasiveness with correspondent
      elevation of MMP-2 and MMP-9. Cytokine-stimulated glioma invasiveness was blocked
      by three pharmacological metalloproteinase inhibitors and by small interfering
      RNAs to MMP-2. Thus, in 3D matrix of CL, MMP-2 expression is modulated by
      inflammatory cytokines with the concomitant increase in glioma invasiveness.

PMID- 18802742
TI  - Mast cells and the adaptive immune response.
AB  - BACKGROUND: The idea that the innate and adaptive immune systems are not separate
      entities is no longer new. In fact, it is surprising that this paradigm was
      accepted without question for so long. Many innate cells express cell surface
      molecules and soluble mediators that are essential for the development and
      activation of T cells and B cells. Yet among the innate cell populations, mast
      cells may play the major role in regulating adaptive immune cell function.
      DISCUSSION: This role first came to light in studies of mast cells and their
      involvement in the autoimmune disease experimental allergic encephalomyelitis,
      the major rodent model of multiple sclerosis and has subsequently been verified
      in many in vitro and in vivo model systems.

PMID- 18802743
TI  - Neuroprotective effect of N-acetylcysteine in the development of diabetic
      encephalopathy in streptozotocin-induced diabetes.
AB  - Diabetic encephalopathy is characterized by impaired cognitive functions that
      involve neuronal damage triggered by glucose driven oxidative stress. The
      objective of the present study was to determine whether N-acetylcysteine (NAC)
      supplementation ameliorates learning and memory deficits caused by hyperglycemia
      induced oxidative stress in experimental diabetes. Male Wistar rats (200-250 g)
      were rendered diabetic by a single intraperitoneal injection of streptozotocin
      (50 mg/kg). Cognitive deficits were observed in diabetic animals assessed using
      elevated plus maze test after 8 weeks of induction of diabetes.
      Acetylcholinesterase activity, a marker of cholinergic function, was decreased by
      15.6% in the cerebral cortex, 20.9% in cerebellum and 14.9% in brain stem of
      diabetic rats compared to control rats. There was an increase in lipid
      peroxidation in cerebral cortex (21.97%), cerebellum (20.4%) and brain stem
      (25.5%) of diabetic rats. This was accompanied by decrease in glutathione and
      total thiol content along with decrease in the activities of superoxide
      dismutase, catalase and glutathione reductase. However, glutathione peroxidase
      activity increased by 11.2%, 13.6% and 23.1% in cerebral cortex, cerebellum and
      brain stem respectively, while the activity of glutathione-s-transferase
      decreased only in cerebral cortex (21.7%). Supplementation with NAC (1.4 g/kg/day
      in drinking water) significantly attenuated cognitive deficits and oxidative
      stress in diabetic rats. Our results emphasize the involvement of increased
      oxidative stress in cognitive impairment in diabetic animals and point towards
      the potential beneficial role of NAC as an adjuvant therapy to conventional anti
      hyperglycemic regimens for the prevention and treatment of diabetic
      encephalopathy.

PMID- 18802744
TI  - Comparison of embryological and clinical outcome in GnRH antagonist vs. GnRH
      agonist protocols for in vitro fertilization in PCOS non-obese patients. A
      prospective randomized study.
AB  - PURPOSE: Embryological and clinical efficacy of gonadotropin-releasing hormone
      (GnRH) antagonist and agonist stimulation protocols in non-obese women with
      polycystic ovarian syndrome (PCOS) were compared. METHODS: A prospective
      randomized study. SETTING: Medical University Hospital. PATIENTS: 70 infertile
      PCOS patients; 33 in GnRH antagonist and 37 in GnRH agonist group. RESULTS:
      Similar mature metaphase II oocyte rate (76% vs. 76%) was observed in both
      protocols. Optimal pronuclear morphology zygotes dominated in both groups (64%
      vs. 66%). Transferred embryo quality did not differ in both protocols. No
      significant differences between both protocols were found in delivery rate (p =
      0.481), pregnancy rate (p = 0.810), multiple pregnancy rate (p = 0.501),
      miscarriage rate (p = 0.154), fertilization rate (p = 0.388) and implantation
      rate (p = 1.000). Duration of stimulation and total follicle-stimulating hormone
      (FSH) dose were significantly lower in GnRH antagonist protocol (p = 0.0005).
      CONCLUSIONS: GnRH antagonist and agonist protocols in non-obese PCOS patients
      yield similar embryological and clinical outcomes. Shorter duration of treatment
      and lower FSH requirement in GnRH antagonist group may be financially beneficial
      and therefore attractive for patients.

PMID- 18802745
TI  - Genetic divergence among marine and lagoon Atherina boyeri populations in Greece
      using mtDNA analysis.
AB  - Genetic differentiation and phylogenetic relationships among 15 Atherina boyeri
      populations from several marine and lagoon or lake sites in Greece were
      investigated using mtDNA analysis. PCR-RFLP analysis of 12s, 16s rRNA genes and D
      loop revealed 23 haplotypes. All the lake or lagoon populations, as well as the
      Kymi and Kalymnos populations that originated from sites with lagoonlike
      environmental conditions, showed haplotypes 1-6, clearly distinguishable from the
      marine populations, which exhibited types 7-23. The genetic divergence values
      estimated between the lagoon and the marine populations ranged from 5.55 to
      10.45%. The high genetic differentiation observed between these two types of
      populations is also highlighted by the dendrograms obtained using UPGMA and
      maximum parsimony methods.

PMID- 18802746
TI  - Tissue expression pattern of class II and class V genes found in the Adh complex
      on mouse chromosome 3.
AB  - The alcohol dehydrogenase enzymes in mice and humans are encoded by a linked
      group of genes in the same transcriptional orientation. The enzymes play
      important roles in alcohol metabolism and retinoid signaling and homeostasis. The
      expression patterns at the mRNA level of the mouse Adh4 (class II) gene and the
      recently identified Adh6a and Adh6b genes (class V) are now reported to complete
      this analysis for the entire family. Adh4 is expressed at high levels in liver
      and is detectable in small intestine and testes. Adh6b is expressed in liver but
      Adh6a is not. Adh6a is expressed at high levels in small intestine while Adh6b is
      not. Adh6a expression is detectable in the female adrenal and not at all in the
      male adrenal, but Adh6b is expressed at moderate levels in both sexes. Although
      Adh6a and Adh6b have expression patterns different from each other, neither
      expresses like any other gene in the complex, suggesting different control
      mechanisms and possibly different functions.

PMID- 18802747
TI  - Effect of capsaicin on ligand binding activity of the hippocampal serotonin1A
      receptor.
AB  - The serotonin(1A) receptor is an important member of the G-protein coupled
      receptor family, and is involved in the generation and modulation of a variety of
      cognitive, behavioral, and developmental functions. In order to examine the role
      of membrane material properties in ligand binding activity of the hippocampal
      serotonin(1A) receptor, we monitored the function of the receptor in presence of
      capsaicin. Capsaicin has been previously shown to increase the elasticity of
      membrane bilayers. Our results show that the ligand binding activity of the
      hippocampal serotonin(1A) receptor is reduced in the presence of capsaicin in a
      linear concentration-dependent manner. This is accompanied by no appreciable
      change in G-protein coupling of the receptor and overall membrane order. We
      conclude that material properties of membrane bilayers could play an important
      role in the function of the serotonin(1A) receptor in particular, and membrane
      proteins in general.

PMID- 18802748
TI  - The influence of a toxic cyanobacterial bloom and water hydrology on algal
      populations and macroinvertebrate abundance in the upper littoral zone of Lake
      Krugersdrift, South Africa.
AB  - The biological interactions and the physical and chemical properties of the
      littoral zone of Lake Krugersdrift were studied for a 4-month period when a
      dense, toxic cyanobacterial bloom dominated by Microcystis aeruginosa was present
      in the main lake basin. The presence of a toxic strain of M. aeruginosa was
      confirmed through the use of ELISA and molecular markers that detect the presence
      of the mcyB and mcyD genes of the mcy gene cluster that synthesizes microcystin.
      An increase in Microcystis toxicity at sites dominated by the cyanobacterial scum
      was accompanied by an increase in total abundance of the macroinvertebrate
      families Hirudinae, Chironomidae, and Tubificidae. Sites located away from the
      cyanobacterial scum had a lower abundance but a higher diversity of
      macroinvertebrates. The water quality under the Microcystis scum was
      characterized by low pH values, low concentrations of dissolved oxygen, and lower
      total alkalinity values. The periphytic alga Ulothrix zonata was absent in areas
      dominated by the cyanobacterial scum, possibly as a result of overshadowing by
      the scum or direct toxic allelopathic effects on growth and photosynthesis. The
      diatom Diatoma vulgare dominated the benthic algal flora beneath the
      cyanobacterial scum.

PMID- 18802749
TI  - Peripheral nerve injury induces down-regulation of Foxo3a and p27kip1 in rat
      dorsal root ganglia.
AB  - FOXO3a, as a forkhead transcription factor, can control cell cycle through
      transcriptionally down-regulating p27(kip1) level, which is a key regulator of
      the mammalian cell cycle and a good candidate to regulate multiple aspects of
      neurogenesis. To elucidate their expression and function in nervous system lesion
      and repair, we performed an acute sciatic nerve crush model and studied
      differential expressions of Foxo3a and p27(kip1) in lumbar dorsal root ganglia.
      Temporally, Foxo3a protein level was reduced 1 day after injury, and following
      Foxo3a down-regulation, p27(kip1) mRNA and protein levels were also decreased
      after injury. Spatially, decreased levels of Foxo3a and p27(kip1) were
      predominant in neurons and glial cells, which were regenerating axons and largely
      proliferated after injury, respectively. Together with previous reports, we
      hypothesized decreased levels of Foxo3a and p27(kip1) in lumbar dorsal root
      ganglia were implicated in axonal regeneration and the proliferation of glial
      cells after sciatic nerve injury.

PMID- 18802750
TI  - Protein kinase C regulates the expression of M1 receptors and BDNF in rat retinal
      cells.
AB  - Protein kinase C (PKC) plays a key role in cellular events including
      proliferation, survival and differentiation. Our previous study showed the effect
      of phorbol 12-myristate 13-acetate (PMA), a PKC activator, inducing a decrease in
      retinal cells proliferation. This effect was mediated by muscarinic type 1
      receptors (M1) activation and brain derived neurotrophic factor (BDNF) treatment
      also induced a decrease in cell proliferation. Based on these results we analyzed
      the expression of either M1 receptors or BDNF following PMA treatment of retinal
      cell cultures. Our data demonstrated that PMA induced a decrease in both protein
      expressions after 48 h in culture. However, after 45 min, PMA induced a transient
      increase in BDNF expression and a decrease in M1 receptors expression. Analyzing
      the expression of M1 receptors and BDNF during the postnatal development in vivo,
      we observed a decrease in both proteins. Taken together our results suggest the
      involvement of PKC in the control of M1 expression in retinal cells.

PMID- 18802751
TI  - Protective effects of asiatic acid on rotenone- or H2O2-induced injury in SH-SY5Y
      cells.
AB  - Parkinson's disease (PD) is a progressive neurodegenerative disorder with a
      prevalence of 1-2% in people over the age of 50. Mitochondrial dysfunction
      occurred in PD patients showing a 15-30% loss of activity in complex I. Asiatic
      acid (AA), a triterpenoid, is an antioxidant and used for depression treatment,
      but the effect of AA against PD-like damage has never been reported. In the
      present study, we investigated the protective effects of AA against H(2)O(2) or
      rotenone-induced cellular injury and mitochondrial dysfunction in SH-SY5Y cells.
      Mitochondrial membrane potential (MMP) and the expression of voltage-dependent
      anion channel (VDAC) were detected with or without AA pretreatment following
      cellular injury to address the possible mechanisms of AA neuroprotection. The
      results showed that pre-treatment of AA (0.01-100 nM) protected cells against the
      toxicity induced by rotenone or H(2)O(2). In addition, MMP dissipation occurred
      following the exposure of rotenone, which could be prevented by AA treatment.
      More interestingly, pre-administration of AA inhibited the elevation of VDAC mRNA
      and protein levels induced by rotenone(100 nM) or H(2)O(2) (300 microM).These
      data indicate that AA could protect neuronal cells against mitochondrial
      dysfunctional injury and suggest that AA might be developed as an agent for PD
      prevention or therapy.

PMID- 18802752
TI  - Prenatal stress causes oxidative damage to mitochondrial DNA in hippocampus of
      offspring rats.
AB  - Mitochondrion, the primary source of reactive oxygen species (ROS), is also the
      target of ROS. 8-Hydroxy-2'-deoxyguanosine (8-OH-dG) is the major end-product of
      damaged DNA caused by ROS. In our previous studies, we showed that prenatal
      stress (PNS) preferentially caused cognitive dysfunction and increased ROS in the
      hippocampus of female offspring rats. The present study aimed to determine 8-OH
      dG level of mitochondria in order to elucidate the mechanism of hippocampal
      pyramidal neuronal damage and cognitive dysfunction induced by PNS. Pregnant rats
      were divided into two groups: control group (undisturbed) and PNS group (exposed
      to a restraint stress for 7 days at the late stage of gestation). Offspring rats
      were divided into four groups: female-control group, male-control group, female
      stress group, male-stress group and used at 30-day-old after their birth. The
      content of 8-OH-dG was determined by high performance liquid chromatography
      electrochemical detection (HPLC-ECD). The results showed that the contents of 8
      OH-dG in female and male prenatal stressed offspring were significantly higher
      than that in their respective controls (P < 0.001). 8-OH-dG level was
      significantly higher in the female-stress group than in the male-stress group (P
      < 0.05), whereas there was no any gender-dependent difference in the control
      groups. These results suggest that accumulation of oxidative mitochondrial DNA
      damage may play an important role in PNS-induced cognitive dysfunction in female
      offspring rats.

PMID- 18802753
TI  - Synergic co-activation in forearm pronation.
AB  - Co-activations of agonist and antagonist muscles are believed to be present in
      voluntary limb movement. Recent studies indicate that such co-activations are
      either synergic or dyssynergic. The aims of this paper are to (1) develop a novel
      method that can extract both the intensity and frequency information from the
      recordings of the surface electromyograms (EMGs) of involved muscles, and (2)
      investigate if the involved muscles will be under synergic co-activation during
      voluntary forearm pronation for normal subjects and dyssynergic co-activation for
      patients with radial nerve palsy. We examined 11 healthy subjects and 4 patients
      with right-arm radial nerve palsy in this study. For the group of healthy
      subjects, each one of them was asked to perform 30 trials of voluntary forearm
      pronation and then 30 trials of passive pronation as control experiments. As to
      the second group of patients, each one was asked to perform only 15 trials of
      voluntary pronation due to the limitation and durability of their arms. The
      recordings of the surface EMGs included the short and long heads of the biceps
      brachii, the brachialis, the lateral head of the triceps brachii,
      brachioradialis, and pronator teres. Experimental results of the healthy group
      indicated that the surface EMGs of all muscles had no statistically significant
      changes in fractal dimensions (FDs) and spectral frequencies of the control
      experiments during passive pronation. Yet, during the voluntary pronation
      experiments, the surface EMGs of all muscle groups were temporally synchronized
      in frequencies with persistent intensities. Hence, all involved muscle groups
      were in synergic co-activation. Statistical results of the group mean values of
      FDs during rest vs. forearm pronation also revealed significant difference with p
      < 0.01 for healthy subjects. As to the group of patients, their EMGs could still
      have bursting activities, but the synchronized significant frequencies might be
      lacking or the intensities as indicated from their FDs would not be persistent.
      To further compare the FDs among the three different protocols, a mixed-model
      ANOVA and multiple comparison tests were performed. Finally, in order to
      illustrate the advantages of this novel method, we have compared it with the
      detrended fluctuation analysis (DFA). It is believed that this proposed method
      will have the potential to be a biomarker for evaluating dynamical disease in
      neuromuscular disorders.

PMID- 18802754
TI  - Periodic "flow-stop" perfusion microchannel bioreactors for mammalian and human
      embryonic stem cell long-term culture.
AB  - The present study examines the use of automated periodic "flow-stop" perfusion
      systems for long-term culture of mammalian cells in a microchannel bioreactor.
      The method is used to culture Human Foreskin Fibroblasts (HFF) and Human
      Umbilical Vein Endothelial Cells (HUVEC) for long periods of time (>7 d) in a
      microchannel (height 100 mum). Design parameters, mass transport and shear stress
      issues are theoretically examined via numerical simulations. Cell growth and
      morphology are experimentally monitored and an enhanced growth rate was measured
      compared to constant perfusion micro-reactors and to traditional culture in Petri
      dishes. Moreover, we demonstrate the use of the method to co-culture
      undifferentiated colonies of human Embryonic Stem Cells (hESC) on HFF feeder
      cells in microchannels. The successful hESC-HFF co-culture in the microbioreactor
      is achieved due to two vital characteristics of the developed method-short
      temporal exposure to flow followed by long static incubation periods. The short
      pulsed exposure to shear enables shear sensitive cells (e.g., hESC) to withstand
      the medium renewal flow. The long static incubation period may enable secreted
      factors (e.g., feeder cells secreted factors) to accumulate locally. Thus the
      developed method may be suitable for long-term culture of sensitive multi
      cellular complexes in microsystems.

PMID- 18802755
TI  - The question of the fusion of neuron processes.
AB  - The authors, whilst accepting the neuron theory, present data indicating the
      possibility that neuronal syncytia exist when myelin-coated ring-like structures
      form in the dendritic field, in nerve arcades close to neuron bodies, and on
      formation of thick, straight anastomoses between neuron bodies. Studies using
      computerized time-lapse videomicroscopy in cultures of isolated neurons
      demonstrated the mechanism by which these structures form. This report provides
      the first evidence of the time parameters of the fusion of the processes of a
      single live neuron; the fusion of fragments of an isolated glial-free fiber was
      demonstrated.

PMID- 18802756
TI  - Immunocytochemical detection of neuronal NO synthase in rat brain cells.
AB  - The aims of the present work were to identify the neuronal form of nitric oxide
      synthase (nNOS type I) in brain structures in rats by immunocytochemistry, to
      compare the results with data from histochemical reactions for NADPH-diaphorase,
      and to develop the optimal conditions for fixation for detecting nNOS. The
      product of the histochemical reaction was found to be located strictly in the
      cytoplasm. Immunocytochemical detection of nNOS showed that along with the
      cytoplasmic reaction for nNOS, the nuclei of some neurons and gliocytes were
      immunopositive, though the cytoplasm of these cells gave negative reactions for
      nNOS. Selection of the optimal fixation conditions for specimens and the dilution
      of the primary antibody allowed reductions in the intensity of nuclear nNOS-type
      reactions without affecting the specific reaction of the cytoplasm for nNOS.
      These data provide evidence that the best detection of nNOS in paraffin sections
      is obtained using immersion fixation in Carnoy's fluid or post-fixation in this
      solution after perfusion with 4% paraformaldehyde.

PMID- 18802757
TI  - Dynamics of the remodeling of neural connections in the superior cervical
      ganglion in rats after dosed compression of the preganglionic trunk.
AB  - The aim of the present work was to obtain a quantitative evaluation of post
      traumatic regeneration of nerve cells in the superior cervical ganglion (SCG) by
      measuring the ratio of the number of neurons (N) in the ganglion to the number of
      preganglionic myelinated fibers (F) in the cervical sympathetic trunk (N/F). This
      was addressed using light and electron microscopy. Studies were performed using
      white male rats divided into three groups: intact (aged seven months), age
      controls (aged 19 months), and experimental - one year after compression of the
      sympathetic trunk at the base of the SCG performed at age seven months. N/F in
      intact rats was 1:210. With age, N/F changed to 1:173; the value one year after
      trauma was 1:745. These data led to the conclusion that normalization of the
      structure of the neural connections of the ganglion did not occur. The process of
      post-traumatic regeneration was incomplete and became chronic.

PMID- 18802758
TI  - Vimentin-immunopositive cells in the rat telencephalon after experimental
      ischemic stroke.
AB  - The aim of the present work was to perform immunocytochemical studies of cells
      synthesizing the intermediate filament protein vimentin in the telencephalon of
      intact rats and rats subjected to unilateral permanent occlusion of the middle
      cerebral artery, which models ischemic stroke. In the intact rat brain, vimentin
      containing cells were seen in the brain barriers. At 14 days from occlusion of
      the middle cerebral artery, there were numerous vimentin-immunopositive cells in
      the perifocal damage zone, and these accounted for a significant proportion of
      the cells in the regenerating nervous tissue at the boundary with undamaged
      tissue. The subependymal proliferative zone contained a significant number of
      vimentin-negative small cells, located between the long processes of vimentin
      immunopositive cells running towards the lesioned zone. These data provide
      evidence of the predominant location of vimentin-immunopositive brain cells (in
      both intact and lesioned animals) in the zones forming barrier structures.

PMID- 18802759
TI  - Some aspects of the modular organization of the primary visual cortex of the cat:
      patterns of cytochrome oxidase activity.
AB  - The distribution of the enzyme cytochrome oxidase (CO) in continuous series of
      parasagittal sections from field 17 and frontal sections of the dorsal nucleus of
      the lateral geniculate body (LGB) from normal kittens and adult cats was studied.
      In all cats apart from neonates, layer IV showed regularly alternating areas with
      above-background levels of CO activity ("spots"). There was a significant
      increase in the contrast of the "spots" from days 13 to 21, which was followed by
      a significant decrease from days 48 to 93. These changes coincided with
      ontogenetic changes in the level of visual system plasticity. There were no
      differences in CO activity between layers A and A1 of the dorsal nucleus of the
      LGB. It is suggested that the non-uniform distribution of the level of functional
      activity of neurons in field 17 reflects the formation of columnar cortical
      structures during the critical period of postnatal ontogenesis.

PMID- 18802760
TI  - Lactate dehydrogenase isoenzymes in sympathetic neurons and satellite gliocytes
      in normal conditions and in blockade of nicotinic cholinoreceptors.
AB  - Integral cytophotometry was used to measure lactate dehydrogenase (LDH) and its H
      and M-isoforms in neurons and satellite gliocytes in tissue sections from the
      cranial cervical sympathetic ganglion of the rabbit in normal conditions and
      after experimental partial and complete pharmacological blockade of nicotinic
      cholinoreceptors (n-CR). In normal conditions, both cell types showed both the H
      and M-type isoforms, though the isoenzyme profiles differed--neurons showed a
      dominance of H-isoform activity while the M-isoform was more active in satellite
      gliocytes. In partial and complete blockade, the activity of LDH and its H-and M
      isoforms decreased significantly in proportion to the number of blocked n-CR. In
      satellite gliocytes, increases in the extent of blockade were associated with
      decreases in the activity only of the M-isoform, while the activity of the H
      isoform did not change. In partial blockade, the LDH isoenzyme profile of
      satellite gliocytes shifted towards the neuronal isoform, while in complete
      blockade there was no difference from the LDH isoenzyme profile of intact
      neurons. These data led to the suggestion that the formation of lactate in
      satellite gliocytes is induced by nicotinic cholinergic synapses directly
      involved in neuron-glial interactions and in controlling the activity of the LDH
      enzyme system in sympathetic neurons.

PMID- 18802761
TI  - The retinomotor reaction of the retina of young dog salmon Oncorhynchus keta on
      adaptation to light and the field of a permanent magnet.
AB  - Studies of Pacific Ocean dog salmon fry of the species Oncorhynchus keta
      addressed two retinomotor reactions: after transfer of fish from the dark to the
      light and after placing fish in the field of a permanent magnet (magnetic
      induction, 80 G) in complete darkness. The reactions of photoreceptors and the
      pigment epithelium (PE) to the magnetic field were analogous to those of the
      retinal reaction on adaptation to light. The morphological characteristics of
      photoreceptors and retinal PE cells lead to the view that the effect of the field
      of a permanent magnet on the retina of young dog salmon is comparable to that of
      light.

PMID- 18802762
TI  - Variants in the structure and topography of the superior margin of the epidural
      space of the human spinal cord.
AB  - Variants in the structure of the upper margin of the epidural space at sites of
      transition from the dura mater of the spinal cord to the dura mater of the brain
      were studied. Stereoepidurographic (88 observations) and corrosion studies (49
      observations) identified four levels for the position of the upper margin of the
      anterior section (intracranially located, lower edge of the occipital bone,
      bodies of C1 and C2) along with five levels for the posterior section (occipital
      bone, occipital bone-arch of C1, C1, C1-C2, C2) of the epidural space. Variants
      on the shape of the upper margin of the anterior (falciform, oval, and dentate in
      the frontal plane; pointed, flexed spurs, pointed slits, and olive-shaped in the
      sagittal plane) and posterior (collar-shaped, oval, and bidentate forks with
      prongs of equal length and forks with prongs of unequal lengths) sections of the
      epidural space arose as a result of asymmetry in the attachment of the upper
      sections of the sac of the dura mater of the spinal cord to the walls of the
      vertebral canal. Weak areas of the upper wall of the epidural space (sites of
      transition from the dura mater of the spinal cord to the dura mater of the brain,
      paravasal capsule of the vertebral artery, the area of the first intervertebral
      foramen) were seen.

PMID- 18802763
TI  - Morphofunctional characteristics of the lumbar enlargement of the spinal cord in
      rats.
AB  - The topography of the lumbar enlargement of the spinal cord in rats was studied;
      an immunohistochemical method was used to determine the distribution of
      synaptophysin--a membrane protein of synaptic vesicles. Synaptophysin
      immunoreactive structures were detected in the gray matter of all Rexed laminae,
      around most neurons and in the neuropil. Previously undescribed subpial synaptic
      contacts were detected immunohistochemically in the white matter and confirmed by
      electron microscopy. A non-myelinated component of the corticospinal tract,
      including axonal varicosities and synaptic contacts, was observed in the dorsal
      part of the white matter of the lumbar enlargement of the spinal cord.

PMID- 18802764
TI  - Embryonic morphogenesis of the human pituitary.
AB  - Light microscopy methods were used to study the main stages in the organogenesis
      of the pituitary in human embryos at Carnegie stages (CS) 12-23. Rathke's pouch
      (RP) was shown to form as a traction fold over whole width of the roof of the
      stomodeum in embryos at CS 12 due to a flexure of the neural tube with which the
      epithelium had a tight anatomical relationship (the attached part of the anterior
      wall of the RP) in the median plane of the embryo. The rudiment of the
      hypothalamic infundibulum and neurohypophysis formed at CS 15, as a thickening of
      the posterior wall of the diencephalon. Transorientation of the positions of
      brain components, including the rudiment of the hypophysis, occurred at CS 20-23.
      The attached part of the anterior wall of the RP then formed the pars intermedia
      and pars tuberalis of the anterior lobe, while the epithelium of the orifice of
      the RP and its posterior wall formed the pars distalis. From CS 20 to 23, the RP
      epithelium formed the structural-functional units of the adenohypophysis, i.e.,
      the epithelial cords, by invagination.

PMID- 18802765
TI  - Morphological changes in the retina in Pacific ocean salmon Oncorhynchus masou
      fry in response to neutralization of the geomagnetic field in conditions of
      normal illumination.
AB  - The studies reported here provide the first demonstration that retinal responses
      in both the fry of the migratory salmon trout Oncorhynchus masou and the dwarf
      form of this species changed in conditions of experimental neutralization of the
      geomagnetic field (GMF); migratory salmon trout fry and dwarves showed different
      changes. The responses of different types of retinal photoreceptor in migratory
      salmon trout fry to neutralization of the GMF differed: while rods and double
      cones perceived neutralization of the GMF as the onset of darkness (the scotopic
      reaction), single (generally blue-sensitive) cones responded to neutralization of
      the GMF both as presentation of blue light or (very rarely) ultraviolet
      irradiation. The retina of dwarf male salmon trout responded to neutralization of
      the GMF with a double response: rods showed a light (photopic) response, while
      double (red/green-sensitive) cones produced dark (scotopic) responses. Single
      (blue-sensitive) cones responded to neutralization of the GMF as bright blue
      light. Thus, the morphological picture of the retina in dwarf male salmon trout
      in these experimental conditions corresponds to the perception of blue light. The
      initial conditions were different--normal diffuse daylight with a brightness of
      about 7.5 Lx. It is likely that neutralization of the magnetic field had no
      effect on rods, while double, red-green, cones responded as to darkness, i.e.,
      the fish did not perceive red or green light in the visible spectrum, but
      perceived only blue and, possibly, ultraviolet light by means of central blue
      sensitive and accessory cones. Thus, these experiments demonstrated that in
      conditions of normal daylight illumination, retinal photoreceptors in salmon fry
      respond to changes in the earth's magnetic field, i.e., objectively function as
      magnetoreceptors.

PMID- 18802766
TI  - Reorganization of the vestibulothalamic projections in lesions to the
      interpositus nucleus of the cerebellum and the vestibular nucleus of Deiters.
AB  - The potential for plastic reorganization in the vestibulothalamic system was
      studied in adult cats. Preliminary (three months) lesioning of the contralateral
      nucleus interpositus of the cerebellum or the lateral vestibular nucleus of
      Deiters led to reorganization of vestibulothalamic projections with formation of
      ipsilateral projections to the ventrolateral nucleus of the thalamus from the
      nuclei of the vestibular complex, along with changes in the normal representation
      of the contralateral projections of the vestibular complex to this thalamic
      nucleus. The distribution and morphological composition of cells in the
      vestibular nuclei forming the new projections to the ventrolateral nucleus of the
      thalamus were studied.

PMID- 18802767
TI  - Metabolic changes in rat brain histaminergic neurons during subhepatic
      cholestasis.
AB  - The aim of the present work was to assess metabolic changes in histaminergic
      neurons in the rat brain during subhepatic cholestasis. Studies were performed on
      male Wistar rats using quantitative histochemical methods. The results showed
      that in cholestasis, histaminergic neurons in the rat hypothalamus developed
      significant changes in succinate dehydrogenase, lactate dehydrogenase, and
      glucose-6-phosphate dehydrogenase activity, in NADH and NADPH, and in acid
      phosphatase and monoamine oxidase B. These changes depended on the duration of
      cholestasis and had a dynamic, wave-like nature. The changes were apparent after
      five days of cholestasis, reached a maximum at 10-20 days, decreased at 45 days,
      and completely disappeared at 90 days.

PMID- 18802768
TI  - Experience in the use of Actovegin in the treatment of patients with cognitive
      disorders in the acute period of stroke.
AB  - Forty-three patients with mild-moderate ischemic stroke were studied in the acute
      period and were divided into two groups. The experimental group consisted of 32
      patients who were given Actovegin; the reference group consisted of 11 patients
      who were given piracetam. Patients were investigated before treatment and at 10
      and 30 days; investigations included examination, points assessments of
      neurological disorders using the original Gusev-Skvortsova scale,
      neuropsychological tests using the MMSE scale, rheoencephalography, and
      electroencephalography. Analysis of changes in clinical features in patients
      treated with Actovegin during the acute period showed that Actovegin had clear
      positive effects both on general cerebral and on focal neurological symptoms. By
      the end of treatment, the extent of recovery of impaired functions, assessed in
      terms of total ischemic points and cognitive functions, was significantly greater
      in patients treated with Actovegin than in patients given piracetam. These data
      lead to the conclusion that Actovegin is effective in the treatment of patients
      with ischemic stroke.

PMID- 18802769
TI  - Motor recover during the acute period of craniocerebral trauma using
      kinetotherapy.
AB  - The aim of the present work was to assess the influences of age, gender, and the
      severity of brain trauma on recovery of motor function using kinetotherapy. The
      study included 131 patients (99 men and 32 women) investigated during the acute
      phase of trauma in the Department of Brain Trauma, Clinical Hospital, Kaunas
      Medical University. After stabilization, 80 patients were transferred to the
      neurorehabilitation clinic and 51 were transferred to other rehabilitation
      centers. Motor function in the patients was assessed using the Clinical Outcomes
      Variable Scale (COVS) at the beginning and end of the acute trauma period and
      during early rehabilitation, i.e., at the beginning, 25 days later, and on
      completion. During the acute trauma period, patients had impairments to the
      abilities to turn over, sit, maintain balance while sitting, to move horizontally
      and vertically, walk, and use mobility aids, along with reductions in walking
      duration and speed, and difficulty in wheelchair mobility and hand functions.
      Kinetotherapy yielded high or intermediate levels of efficacy in 90% of the
      patients. The efficacy of kinetotherapy was significantly greater in young
      patients than in elderly and old patients (p < 0.05). Gender and trauma severity
      had no statistically significant effects on the efficacy of kinetotherapy (p >
      0.05).

PMID- 18802770
TI  - Activity of the positive and negative reinforcement motivation systems and
      baseline arterial blood pressure in humans.
AB  - The aim of the present work was to identify possible associations between
      individual balances in the activity of the positive and negative reinforcement
      motivation systems using a method based on emotional modulation of the startle
      reaction (EMSR) by motivationally significant emotionally positive and negative
      contextual visual stimuli and measures of cardiovascular system activity. Studies
      were performed using healthy males (mean age 30.29 +/- 9.8 years) with normal and
      first-episode excessive increases in arterial blood pressure (systolic blood
      pressure to greater than 140 mmHg, diastolic to greater than 90 mmHg). Cluster
      analysis of EMSR data identified groups of individuals with different activity
      profiles for the positive and negative reinforcement systems. Groups of subjects
      with changes in the balance of activity towards a lower level of positive
      reinforcement system activity (smaller startle reflexes to positive contextual
      stimuli) or a higher level of negative reinforcement system activity (larger
      startle reactions to threatening contextual stimuli) showed significantly greater
      baseline SBP and DBP. The possible mechanisms of the modulatory influences of the
      balance of system activities on autonomic vascular regulatory processes are
      discussed.

PMID- 18802771
TI  - Relationship between the types of behavioral reaction in a conditioned shake-off
      reflex and neocortical lateralization.
AB  - The nature of the spike activity and interhemisphere interactions of neurons in
      the parietal cortex (somatosensory representation of the ear) during the
      intersignal period before active shake-off and passive (freezing) reactions to
      stimuli was studied in rabbits after acquisition of a conditioned defensive
      escape reflex. Before passive reactions, in contrast to the situation before
      active shake-off, there were increases in right-sided influences on cells in the
      left hemisphere with delays of up to 100 msec, leading to asymmetry in
      interhemisphere interactions with right-sided dominance. Passive reactions were
      preceded by increases in the extent of frequencies in the delta range in the
      spike activity of individual neurons and in interactions between pairs of cells.
      These data provide evidence that the existence and nature of interhemisphere
      asymmetry before stimulation is one of the factors determining the passive or
      active type of behavioral reaction and reflecting the level of activation of the
      cortex.

PMID- 18802772
TI  - The dopaminergic nigrostriatal system in sleep deprivation in cats.
AB  - The dynamics of changes in electrophysiological measures of the sleep-waking
      cycle were analyzed in Wistar rats after 6 h of sleep deprivation by gentle
      waking and subsequent 9-h post-deprivation sleep. A delayed sleep "overshoot"
      reaction was observed 2.5-3 h after sleep deprivation, as a moderate increase in
      the proportions of slow-wave and fast-wave sleep in the sleep-waking cycle.
      Immunohistochemical studies were performed in relation to changes in the sleep
      waking cycle, with the aim of identifying changes in the quantities of
      immunoreactive dopamine D1 and D2 receptor material and tyrosine hydroxylase, the
      key enzyme in dopamine synthesis in the nigrostriatal system. In conditions of
      sleep deprivation, the caudate nucleus showed increases in the quantities of
      dopamine D1 and D2 receptor material, while there was a simultaneous decrease in
      the amount of immunoreactive material in the substantia nigra. Post-deprivation
      sleep was accompanied by decreases in the quantities of immunoreactive D1
      receptor material and increases in D2 receptor material in the caudate nucleus,
      with an increase in the quantity of immunoreactive tyrosine hydroxylase in the
      substantia nigra. These data provide evidence of the active role of the
      dopaminergic nigrostriatal system which, along with other CNS transmitter
      systems, supports telencephalic-diencephalic interactions, in the sleep-waking
      cycle.

PMID- 18802773
TI  - Changes in anxiety after administration of cortisol to rats selected for the
      ability to acquire active avoidance.

PMID- 18802774
TI  - Contribution of GABA receptors to extinction of memory traces in normal
      conditions and in a depression-like state.
AB  - A relationship between the effects of activation and blockade of GABA receptors
      on extinction of a conditioned passive avoidance reaction on the one hand and the
      type of receptor and initial psychoemotional state on the other was found in
      mice. Activation of GABA(A) receptors with muscimol impaired extinction in normal
      conditions but had no effect on the delay in this process in mice with
      "behavioral despair" reactions. Activation of GABA(B) receptors with baclofen
      accelerated extinction of the memory of fear in mice with the depression-like
      state. Blockade of GABA(A) receptors with bicuculline had no extinction-modifying
      effect. Blockade of GABA(B) receptors with faclofen promoted retention of the
      expression of fear in intact mice and acceleration of extinction in "depressed"
      mice.

PMID- 18802775
TI  - The role of hypothalamo-hypophyseal-adrenocortical system hormones in controlling
      pain sensitivity.
AB  - The present review addresses analysis of data demonstrating the role of the
      hypothalamo-hypophyseal-adrenocortical axis (HHACA) in controlling pain
      sensitivity. Experiments on rats have demonstrated the analgesic effects of
      exogenous hormones of all components of the HHACA - corticotropin-releasing
      hormone (CRH), adrenocorticotropic hormone (ACTH), and glucocorticoids - in the
      same models, and have also shown that the opioid and non-opioid mechanisms
      contribute to the development of the analgesia induced by these hormones.
      Endogenous glucocorticoids are involved in the development of analgesia mediated
      by non-opioid mechanisms. Along with the non-opioid mechanisms associated with
      endogenous glucocorticoids, the analgesic effect of ACTH can be mediated by the
      opioid mechanism. Unlike the situation with ACTH, the analgesic effect of CRH is
      mediated exclusively by non-opioid mechanisms, one of which is associated with
      HHACA hormones, while the other, appearing only on systemic administration, is
      not associated with these hormones. The actions of glucocorticoids on pain are
      mediated by neurons in the central gray matter of the midbrain.

PMID- 18802776
TI  - The hippocampus and cognitive impairments.
AB  - Progressive increases in the worldwide number of cases of brain diseases
      accompanied by cognitive impairments continually reinforce the relevance of the
      need for further investigation and pharmacotherapy of this type of neuromental
      pathology, particularly as this problem has great significance, not only in the
      medical sphere, but also in the social. This explains the currently extensive
      interest of investigators of different specialties in studies of the role of the
      hippocampus (HPO) in the genesis of these disorders and the possibility that
      nootropic substances have influences on it.

PMID- 18802777
TI  - Natural kinds in evolution and systematics: metaphysical and epistemological
      considerations.
AB  - Despite the traditional focus on metaphysical issues in discussions of natural
      kinds in biology, epistemological considerations are at least as important. By
      revisiting the debate as to whether taxa are kinds or individuals, I argue that
      both accounts are metaphysically compatible, but that one or the other approach
      can be pragmatically preferable depending on the epistemic context. Recent
      objections against construing species as homeostatic property cluster kinds are
      also addressed. The second part of the paper broadens the perspective by
      considering homologues as another example of natural kinds, comparing them with
      analogues as functionally defined kinds. Given that there are various types of
      natural kinds, I discuss the different theoretical purposes served by diverse
      kind concepts, suggesting that there is no clear-cut distinction between natural
      kinds and other kinds, such as functional kinds. Rather than attempting to offer
      a unique metaphysical account of 'natural' kind, a more fruitful approach
      consists in the epistemological study of how different natural kind concepts are
      employed in scientific reasoning.

PMID- 18802778
TI  - Transposition of a 600 thousand-year-old LTR retrotransposon in the model legume
      Lotus japonicus.
AB  - We have identified a new Ty3-gypsy retrotransposon family named LORE2 (Lotus
      retrotransposon 2) and documented its activity in the model legume Lotus
      japonicus. Three new LORE2 insertions were found in symbiotic mutant alleles
      isolated from a plant population, established by tissue culture mediated
      transformation of the L. japonicus Gifu accession. Low transcriptional and
      transpositional activities of LORE2 in cultured cells suggested that the LORE2
      transpositions identified in the three symbiotic mutants occurred in intact
      plants, not in callus. Tracing of the transpositional events identified two
      active LORE2 members in Gifu. One of them named LORE2A possesses a deletion in
      its coding region and polymorphisms between intraelemental LTRs. LORE2A is thus
      an aged element, estimated as 600 thousand years old. Our findings indicate that
      plant genomes carry more cryptic LTR retrotransposons, i.e., aged yet active,
      than estimated before, and that these cryptic elements may have contributed to
      plant genome dynamics, for example, the burst of transpositions reported in
      several plant species.

PMID- 18802779
TI  - Accuracy of self-reports of Pap and mammography screening compared to medical
      record: a meta-analysis.
AB  - OBJECTIVES: To conduct a systematic review and meta-analysis of the accuracy of
      self-reported Pap smear and mammography screening compared to medical record.
      METHODS: About 37 articles were reviewed and accuracy indices of self-report were
      calculated. Meta-analysis with random effects was used. Study heterogeneity was
      investigated and meta-regressions were done including in the models those factors
      that were hypothesized, a priori, to potentially explain heterogeneity. RESULTS:
      Pooled sensitivity and specificity for Pap recall were 94.7% (95% confidence
      interval [CI]; 93.0%-96.4%) and 47.4% (95% CI; 39.0%-55.7%), and for mammography
      were 94.9% (95% CI; 93.4%-96.4%) and 61.8% (95% CI; 54.1%-69.5%), respectively.
      There was significant heterogeneity for all indices. Stratifying by the study
      population source (population versus clinic-based), population characteristics
      (minority or low socio-economic status versus not), length of recall (within past
      12 months versus longer), and expected completeness of the medical record
      (authors searched radiology or pathology reports of all likely facilities women
      may have attended, versus studies that did not) did not eliminate heterogeneity.
      CONCLUSIONS: Women tend to over-report their participation in Pap and mammography
      screening in a given timeframe. The pooled estimates should be interpreted with
      caution due to unexplained heterogeneity.

PMID- 18802780
TI  - Common genetic polymorphisms of AURKA and prostate cancer risk.
AB  - PURPOSE: AURKA is a centrosome-associated serine/threonine kinase involved in
      mitotic chromosomal segregation. The AURKA gene is located on chromosome 20q13,
      also known as HPC20 prostate cancer susceptibility locus. Therefore, we
      investigated in this Caucasian case-control study two single nucleotide
      polymorphisms (SNPs) of the AURKA gene, rs8173 located in the 3'-untranslated
      region (G1891C) and rs2273535 in exon 5 (Phe31Ile), and their association with
      prostate cancer risk. METHODS: DNA was extracted from peripheral blood of 824
      prostate cancer patients and 1,081 control patients with benign prostatic
      hyperplasia (BPH). Genotypes were determined using 5'-nuclease TaqMan assays.
      Multiple logistic regressions were performed to calculate odds ratios (OR) and
      confidence intervals (CI) and to adjust for confounders. RESULTS: The odds ratios
      calculated relative to the wild-type were for the homozygous polymorphic
      genotypes 1.11 (95% CI = 0.70-1.76) for rs8173 and 1.32 (95% CI = 0.76-2.31) for
      rs2273535, respectively. Stratified analyses according to Gleason score showed
      also no statistically significant association for the investigated polymorphisms
      and prostate cancer risk. CONCLUSIONS: The two investigated SNPs in AURKA were
      not found to be associated with prostate cancer risk. Other common SNPs of AURKA
      should be investigated in further studies because of its location on a prostate
      cancer susceptibility locus.

PMID- 18802781
TI  - Linking multimetric and multivariate approaches to assess the ecological
      condition of streams.
AB  - Few attempts have been made to combine multimetric and multivariate analyses for
      bioassessment despite recognition that an integrated method could yield powerful
      tools for bioassessment. An approach is described that integrates eight
      macroinvertebrate community metrics into a Principal Components Analysis to
      develop a Multivariate Condition Score (MCS) from a calibration dataset of 511
      samples. The MCS is compared to an Index of Biotic Integrity (IBI) derived using
      the same metrics based on the ratio to the reference site mean. Both approaches
      were highly correlated although the MCS appeared to offer greater potential for
      discriminating a wider range of impaired conditions. Both the MCS and IBI
      displayed low temporal variability within reference sites, and were able to
      distinguish between reference conditions and low levels of catchment modification
      and local habitat degradation, although neither discriminated among three levels
      of low impact. Pseudosamples developed to test the response of the metric
      aggregation approaches to organic enrichment, urban, mining, pastoral and logging
      stressor scenarios ranked pressures in the same order, but the MCS provided a
      lower score for the urban scenario and a higher score for the pastoral scenario.
      The MCS was calculated for an independent test dataset of urban and reference
      sites, and yielded similar results to the IBI. Although both methods performed
      comparably, the MCS approach may have some advantages because it removes the
      subjectivity of assigning thresholds for scoring biological condition, and it
      appears to discriminate a wider range of degraded conditions.

PMID- 18802782
TI  - Evaluation of a training and communication-network nephrology program for
      community pharmacists.
AB  - OBJECTIVES: To assess the feasibility and impact of implementing ProFiL program
      to optimize community-pharmacist management of drug-related problems among
      chronic kidney disease patients followed in a predialysis clinic. The program
      comprises a training workshop, communication-network program and consultation
      service. SETTING: Forty-two community pharmacies, 101 pharmacists, and 90 chronic
      kidney disease patients attending a predialysis clinic in Laval (Canada).
      Patients were followed-up for 6 months. METHOD: In a six-month, pilot, open,
      cluster-randomized controlled trial, community pharmacies were assigned to ProFiL
      or the usual care. Chronic kidney disease patients of these pharmacies attending
      a predialysis clinic were recruited. ProFiL pharmacists attended a workshop,
      received patient information (diagnoses, medications, and laboratory-test
      results) and had access to a consultation service. Their knowledge and
      satisfaction were measured before and after the workshop. The mean numbers of
      pharmacists' written recommendations to physicians (pharmaceutical opinions) and
      refusals to dispense a medication were computed. RESULTS: Of the ProFiL
      pharmacists, 84% attended the workshop; their knowledge increased from 52% to 88%
      (95% CI: 29-40%). Most ProFiL pharmacists rated workshop (95%), communication
      program (82%) and consultation service (59%) as "excellent" or "very good"; 82%
      said the program improved the quality of their follow-up. The consultation
      service received 21 requests. ProFiL and usual care pharmacists issued a mean of
      0.50 and 0.02 opinion/patient, respectively, (95% CI of the adjusted difference:
      0.28-1.01 opinion/patient). CONCLUSION: The results of this pilot study suggest
      that ProFiL can be implemented and may help community pharmacists intervene more
      frequently to manage drug-related problems. However, a larger-scale study with
      longer follow-up is necessary to evaluate the impact of the program on management
      of drug-related problems and its clinical relevance.

PMID- 18802783
TI  - First renin inhibitor, aliskiren, for the treatment of hypertension.
AB  - AIM OF THE REVIEW: To systematically analyze the efficacy and safety of aliskiren
      for the treatment of hypertension in comparison to placebo, other monotherapy,
      and various combination therapies. METHOD: A PubMed database (1966-June 2008)
      search was conducted with aliskiren as a search term with limits of humans,
      written in English, and in title only. Phase III pivotal clinical studies
      retrieved by PubMed database and resources such as printed labeling, approval
      letter, pharmacology reviews, and medical reviews posted in Drug@FDA website were
      evaluated with regard to study design and outcomes of efficacy and safety.
      RESULTS: Six Phase III pivotal clinical studies compared various doses of
      aliskiren to placebo and some studies compared aliskiren to treatment with other
      monotherapies or combinations. Aliskiren in doses of 300 mg showed a
      statistically significant reduction in both systolic and diastolic blood pressure
      versus placebo. Comparison to other antihypertensive treatments suggest that
      aliskiren doses of 150 and 300 mg may induce blood pressure changes similar to
      those seen with moderate doses of hydrochlorothiazide or angiotensin receptor
      blockers. Aliskiren in combination with angiotensin receptor blockers or
      hydrochlorothiazide showed additional blood pressure reduction only when higher
      doses of aliskiren were used. Aliskiren appears to be well tolerated, with
      diarrhea being the only statistically significant adverse event. CONCLUSION:
      Aliskiren is a novel antihypertensive that exerts its effects through the direct
      inhibition of renin. Although the drug is well tolerated, its modest effects on
      blood pressure and the present lack of evidence of impact on objective
      cardiovascular outcomes appear to limit its utility in the general treatment of
      hypertension at this time.

PMID- 18802784
TI  - Biomedicine: an ontological dissection.
AB  - Though ubiquitous across the medical social sciences literature, the term
      "biomedicine" as an analytical concept remains remarkably slippery. It is argued
      here that this imprecision is due in part to the fact that biomedicine is
      comprised of three interrelated ontological spheres, each of which frames
      biomedicine as a distinct subject of investigation. This suggests that, depending
      upon one's ontological commitment, the meaning of biomedicine will shift. From an
      empirical perspective, biomedicine takes on the appearance of a scientific
      enterprise and is defined as a derivative category of Western science more
      generally. From an interpretive perspective, biomedicine represents a symbolic
      cultural expression whose adherence to the principles of scientific objectivity
      conceals an ideological agenda. From a conceptual perspective, biomedicine
      represents an expression of social power that reflects structures of power and
      privilege within capitalist society. No one perspective exists in isolation and
      so the image of biomedicine from any one presents an incomplete understanding. It
      is the mutually-conditioning interrelations between these ontological spheres
      that account for biomedicine's ongoing development. Thus, the ontological
      dissection of biomedicine that follows, with particular emphasis on the period of
      its formal crystallization in the latter nineteenth and early twentieth century,
      is intended to deepen our understanding of biomedicine as an analytical concept
      across the medical social sciences literature.

PMID- 18802785
TI  - A problem for achieving informed choice.
AB  - Most agree that, if all else is equal, patients should be provided with enough
      information about proposed medical therapies to allow them to make an informed
      decision about what, if anything, they wish to receive. This is the principle of
      informed choice; it is closely related to the notion of informed consent.
      Contemporary clinical trials are analysed according to classical statistics. This
      paper puts forward the argument that classical statistics does not provide the
      right sort of information for informing choice. The notion of probability used by
      classical statistics is complex and difficult to communicate. Therapeutic
      decisions are best informed by statistical approaches that assign probabilities
      to hypotheses about the benefits and harms of therapies. Bayesian approaches to
      statistical inference provide such probabilities.

PMID- 18802786
TI  - Longitudinal factorial invariance of the PedsQL 4.0 Generic Core Scales child
      self-report Version: one year prospective evidence from the California State
      Children's Health Insurance Program (SCHIP).
AB  - BACKGROUND: The measurement of health-related quality of life (HRQOL) in
      pediatric medicine and health services research has grown significantly over the
      past decade. The paradigm shift toward patient-reported outcomes (PROs) has
      provided the opportunity to emphasize the value and critical need for pediatric
      patient self-report. In order for changes in HRQOL/PRO outcomes to be meaningful
      over time, it is essential to demonstrate longitudinal factorial invariance. This
      study examined the longitudinal factor structure of the PedsQL 4.0 Generic Core
      Scales over a one-year period for child self-report ages 5-17 in 2,887 children
      from a statewide evaluation of the California State Children's Health Insurance
      Program (SCHIP) utilizing a structural equation modeling framework. METHODS:
      Specifying four- and five-factor measurement models, longitudinal structural
      equation modeling was used to compare factor structures over a one-year interval
      on the PedsQL 4.0 Generic Core Scales. RESULTS: While the four-factor
      conceptually-derived measurement model for the PedsQL 4.0 Generic Core Scales
      produced an acceptable fit, the five-factor empirically-derived measurement model
      from the initial field test of the PedsQL 4.0 Generic Core Scales produced a
      marginally superior fit in comparison to the four-factor model. For the five
      factor measurement model, the best fitting model, strict factorial invariance of
      the PedsQL 4.0 Generic Core Scales across the two measurement occasions was
      supported by the stability of the comparative fit index between the unconstrained
      and constrained models, and several additional indices of practical fit including
      the root mean squared error of approximation, the non-normed fit index, and the
      parsimony normed fit index. CONCLUSION: The findings support an equivalent factor
      structure on the PedsQL 4.0 Generic Core Scales over time. Based on these data,
      it can be concluded that over a one-year period children in our study interpreted
      items on the PedsQL 4.0 Generic Core Scales in a similar manner.

PMID- 18802787
TI  - An olfactory receptor pseudogene whose function emerged in humans: a case study
      in the evolution of structure-function in GPCRs.
AB  - Human olfactory receptor, hOR17-210, is identified as a pseudogene in the human
      genome. Experimental data has shown however, that the gene product of frame
      shifted, cloned hOR17-210 cDNA was able to bind an odorant-binding protein and is
      narrowly tuned for excitation by cyclic ketones. Supported by experimental
      results, we used the bioinformatics methods of sequence analysis (genome-wide and
      pair-wise), computational protein modeling and docking, to show that
      functionality in this receptor is retained due to sequence-structure features not
      previously observed in mammalian ORs. This receptor does not possess the first
      two transmembrane helical domains (of seven typically seen in GPCRs). It however,
      possesses an additional TM that has not been observed in other human olfactory
      receptors. By incorporating these novel structural features, we created two
      putative models for this receptor. We also docked odor ligands that were
      experimentally shown to bind hOR17-210. We show how and why structural
      modifications of OR17-210 do not hinder this receptor's functionality. Our
      studies reveal that novel gene rearrangements that result in sequence and
      structural diversity may have a bearing on OR and GPCR function and evolution.

PMID- 18802788
TI  - Proportionality, just war theory and weapons innovation.
AB  - Just wars are supposed to be proportional responses to aggression: the costs of
      war must not greatly exceed the benefits. This proportionality principle raises a
      corresponding 'interpretation problem': what are the costs and benefits of war,
      how are they to be determined, and a 'measurement problem': how are costs and
      benefits to be balanced? And it raises a problem about scope: how far into the
      future do the states of affairs to be measured stretch? It is argued here that
      weapons innovation always introduces costs, and that these costs cannot be
      determined in advance of going to war. Three examples, the atomic bomb, the AK-47
      and the ancient Greek catapult, are given as examples. It is therefore argued
      that the proportionality principle is inapplicable prospectively. Some replies to
      the argument are discussed and rejected. Some more general defences of the
      proportionality principle are considered and also rejected. Finally, the
      significance of the argument for Just War Theory as a whole is discussed.

PMID- 18802789
TI  - Immunohistochemical study concerning the origin of neurocytoma--a case report.
AB  - A 26-year-old woman presented with rapid tumor growth in her left frontal lobe
      during 9 years of observation. Operative findings revealed a massive tumor
      connected to gelatinous, transparent membranous tissue (MT), which extended from
      the paraventricular zone and continued into the lateral ventricle. Histological
      diagnosis was atypical neurocytoma. Immunohistochemical analyses revealed that
      the tumor was strongly positive for not only neural markers but also a glial
      marker, while the MT was positive for a neural marker. The Ki-67/MIB-1 labeling
      index was 9.1% in the tumor body and 0% in the MT. Musashi 1, a marker of neural
      stem cells, was strongly positive in both the tumor body and the MT. We speculate
      that the tumor growth was due to a rapid decline of the Musashi 1-positive cells
      to glial differentiation. These cells may be candidates for the origin of the
      tumor.

PMID- 18802790
TI  - Heterogeneity of prostate-specific membrane antigen (PSMA) expression in prostate
      carcinoma with distant metastasis.
AB  - Prostate-specific membrane antigen (PSMA) is a transmembrane protein that is
      overexpressed in advanced stage prostate adenocarcinomas. As a novel target for
      in vivo prognostic and therapeutic approaches, the distribution pattern of PSMA
      in primary and metastatic tumors is of significant interest. In this study we
      addressed the cellular distribution and heterogeneity of PSMA expression.
      Paraffin-embedded sections of 51 patients with primary prostate carcinoma and
      distant metastases were evaluated. Immunohistochemistry was used to determine the
      cellular localization, staining intensity and positive cell fraction which were
      related to tumor type and growth pattern. We demonstrated differences in the
      intracellular localization of the PSMA immunostaining which seem to be related to
      the tumor differentiation pattern. A significant number of the primary tumors
      (7/51) and metastases (6/51) presented with highly heterogeneous PSMA expression
      and in further 2 primary, and 8 metastatic tumors the staining was in the
      negative range (<10% positive tumor cells). A direct correlation between
      histological parameters and PSMA expression could not be demonstrated. Our
      findings clearly support the feasibility but also direct to potential failures of
      PSMA-targeted in vivo diagnostic and therapeutic approaches in prostate cancer
      patients with distant metastasis.

PMID- 18802791
TI  - Detection of deregulated pathways to lymphatic metastasis in oral squamous cell
      carcinoma.
AB  - Oral squamous cell carcinoma (OSCC) is a common malignancy, in which lymph node
      metastasis is a major determinant of outcome. The pathway deregulation resulting
      from a large number of somatic genetic alterations in the development of the
      tumor, plays an important role in lymphatic metastasis process. To detect the
      deregulated pathways to lymphatic metastasis in OSCC, we performed pathway
      oriented analysis using gene expression profile from 16 samples without lymphatic
      metastasis and 27 samples with lymphatic metastasis. We identified seven
      significantly (p < 0.05) deregulated pathways: the erythropoietin (EPO) Signaling
      Pathway, Signaling Pathway from G-Protein Families, Cytokine-cytokine receptor
      interaction, the Janus kinase (JAK)-signal transducer and activator of
      transcription (STAT) signaling pathway, Ribosome, Colorectal cancer, B cell
      receptor signaling pathway. The biological relevance of these pathways to OSCC is
      the focus of ongoing studies, as well as complex interactions and crosstalk
      between them. These pathways might provide additional clues about factors that
      regulate the course for OSCC patients and might offer new opportunities for
      therapeutic intervention.

PMID- 18802792
TI  - Voiding symptoms and urodynamic findings in patients with modified ileal
      neobladde.
AB  - The aim of our study was to find the cause of urinary incontinence and voiding
      dysfunction in patients undergoing radical cystectomy and orthotopic bladder
      replacement with modified ileal neobladder (Reddy). Twenty-eight incontinent
      patients (operated on between 1988 and 2004) were involved in our examination.
      Based on the complaints of the patients, continence status was evaluated and
      divided into two groups: group I: partially incontinent (only night-time
      incontinence) n = 11 (39.3%) and group II: totally incontinent (night-time and
      daytime incontinence) n = 17 (60.7%). Detailed urodynamic examination
      (enterocystometry and urethral pressure profile) in addition to involuntary
      neobladder contractions and capacity detection were carried out on all patients.
      Furthermore resting pressure and maximal voluntary contraction ability of the
      sphincter were determined and statistically analyzed in both groups. Significant
      difference was noticed in resting pressure and maximal voluntary contraction
      ability of the sphincter among the partially incontinent and totally incontinent
      patients. Frequency, intensity and duration of involuntary neobladder
      contractions also showed significant differences between the two groups.
      Incontinence of neobladder depends not only on the destruction of resting and
      contraction capability of the urethral sphincter, but also on the presence or
      absence of involuntary contractions in the wall of the neobladder and decreased
      capacity of the neobladder.

PMID- 18802793
TI  - Cysticercosis of the fourth ventricle causing sudden death: a case report and
      review of the literature.
AB  - A 15 years old girl of African origin was admitted with a history of headaches
      and a generalised tonic seizure. Her clinical examination including fundoscopy
      was normal. She claimed she had been assaulted. Within a few hours of her
      admission she was found dead in her bed during the ward round. Cardiopulmonary
      resuscitation was unsuccessful. At post-mortem, the major organs showed no
      pathological changes and neck dissection showed no abnormality. Neuropathological
      examination after formalin fixation revealed a cystic lesion in the fourth
      ventricle, ependymitis and acute hydrocephalus. Histology showed parts of the
      parasite Taenia solium and the diagnosis was neurocysticercosis. This case
      highlights the need for forensic and general pathologists as well as forensic
      medical examiners and paediatricians to be aware of neurocysticercosis as a
      possible cause of sudden death in the presence of normal clinical findings and
      negative autopsy, especially in patients from Asian, African or South American
      countries. As cysticercosis is the commonest cause of seizures in the developing
      world, neurocysticercosis needs to be considered as a cause of sudden and
      unexpected death in any patient with a history of headaches and/or seizures.

PMID- 18802794
TI  - The updated concept of genome and its implications in biotechnological research
      and molecular diagnostics.
AB  - We propose a short definition of GENOME: The full complement of genetic materials
      possessed by an intracellular parasite, a cell, or an organism. Accordingly, the
      human genome is the entire complement of inherited genetic materials possessed by
      an individual person, or possessed by a cell in an individual person. For higher
      species, the genomic makeup includes DNA in the nucleus and in the organelles
      regardless of the number of chromosomes and the homoplasmic or heteroplasmic
      status of the mitochondrial or chloroplastic DNA. Practically, GENOME can be
      referred to at the molecular, cellular, individual, and species levels, which has
      various implications in biotechnological research and molecular diagnostics.

PMID- 18802795
TI  - Haplotypic diversity within the ovine calpastatin (CAST) gene.
AB  - Calpastatin (CAST) is a protein inhibitor that acts specifically on calpains and
      plays a regulatory role in postmortem beef tenderization and muscle proteolysis.
      Polymorphisms in the bovine CAST gene have been associated with meat tenderness,
      but little is known about how the ovine CAST gene may affect sheep meat quality
      traits. In this study, we selected two parts of the ovine CAST gene that have
      been previously reported to be polymorphic (region 1-part of intron 5 and exon 6,
      and region 2-part of intron 12), to investigate haplotype diversity across an
      extended region of the ovine gene. First, we developed a simple and efficient
      polymerase chain reaction-single-strand conformational polymorphism (PCR-SSCP)
      method for genotyping region 2, which allowed the detection of a novel allele as
      well as the three previously reported alleles. Next, we genotyped both regions 1
      and 2 of the ovine CAST gene from a large number of sheep to determine the
      haplotypes present. Nine different haplotypes were found across this extended
      region of the ovine CAST gene and four haplotypes were identified that suggested
      historical recombination events within this gene. Haplotypes are typically more
      informative than single nucleotide polymorphisms (SNPs) for analyzing
      associations between genes and complex production traits, such as meat
      tenderness, but the potential for intragenic recombination within the ovine CAST
      may make finding associations challenging.

PMID- 18802796
TI  - [Patent foramen ovale and migraine: where is the connection].
AB  - Patent foramen ovale (PFO) is an anatomic remnant of the fetal circulation that
      is highly prevalent in the general population. Several observational studies show
      that migraine with aura and PFO have higher coincidences than expected by chance.
      Both conditions might be linked by certain pathophysiological mechanisms, such as
      right-to-left shunting of venous agents or paradoxical embolism. Alternatively,
      they might share a common genetic background. No relevant differences have been
      found between the clinical features of migraine with FOP and those of migraine
      without FOP. The results of several observational studies suggest that PFO
      closure may have a beneficial effect on migraine. However, the first randomized,
      double-blind, and sham-controlled trial has failed to support such conclusion.
      Until there is more evidence from ongoing trials, PFO closure should not be
      performed in clinical practice for the treatment of migraine.

PMID- 18802797
TI  - [Minocycline for the treatment of amyotrophic lateral sclerosis: neuroprotector
      or neurotoxin? Reflections on another failure of translational medicine].
AB  - A recent publication of the results of a clinical trial of minocycline in 412 ALS
      patient has aroused considerable controversy in the ALS scientific community. As
      on previous occasions, the results obtained in the laboratory are not reproduced
      in clinical practice. The reasons for this new disappointment in translational
      medicine are analysed by applying the successes obtained in the experimental
      animal model for ALS to humans. The most frequently suggested causes for
      explaining these continuous failures are unawareness of the correct dosage to be
      used, the ideal duration of the clinical trial in phase III, sample size, the
      search for a primary outcome for measurement other than survival, the need for
      biomarkers giving information on the progression of the disease and whether this
      is modified by the introduction of the drug for study. Debate focuses on whether
      the transgenic mouse model of ALS which expresses SOD1 mutations which we have
      been using for more than a decade is an exact reflection of the clinical profile
      and the physiopathogenic mechanisms present in patients with spo- radic ALS.
      There is the possibility that depending on the dose administered, minocycline can
      be a neuroprotector or a neurotoxin. In other words, at a dose of 200 mg/day,
      this drug behaves like <<Dr. Jekyll>> and like <<Mr. Hyde>> at doses of 400 mg.
      For the authors of the trial, this possibility does not seem to be the cause of
      the disappointing results obtained. However, they acknowledge that one of the
      limitations of their study was that it was impossible to compare the effects of
      minocycline in the patient after receiving 200 or 400 mg. For many other
      researchers running ongoing clinical trials in both ALS and other neurological
      diseases, the dose of 200 mg/day is chosen as ideal for testing the effectiveness
      of minocycline in patients. The strategy of administering the maximum dose of a
      drug to be tested may give rise to misleading results. We agree with the opinion
      of other authors, who say that minocycline should be given a second chance.

PMID- 18802798
TI  - [Frontotemporal lobar degeneration: a descriptive study of 42 patients].
AB  - INTRODUCTION: Frontotemporal lobar degeneration (FTLD) is considered to be the
      second cause of presenile dementia. In spite of the great interest it has
      generated over the last few years, few studies have been published in our
      country. METHODS: A descriptive retrospective study of 42 patients with FTLD
      evaluated in our unit during the period 1996-2006 was performed. RESULTS: Thirty
      one patients presented with frontal variant FTLD (FTD), eigth with non-fluent
      progressive aphasia and three with semantic dementia. Mean age at onset was 56
      years, diagnostic delay 3.5 years and mean survival 6.8 years. 35% had a family
      history suggestive of dementia. In patients with FTD the clinical expression was
      a combination of behavioral and personality disorders together with language
      impairment. Magnetic resonance imaging showed frontal and/or temporal atrophy in
      62% of cases and SPECT showed frontal and/or temporal hypoperfusion in 75%. The
      P301L tau mutation was detected in four patients (two of them siblings) and the
      A303AfsX57 progranulin mutation in one. Necropsy was performed in five patients,
      revealing FTLD with ubiquitininmunoreactive inclusions (FTLD-U) and motor neuron
      disease in two cases, FTLD-U with <<cat's-eye>> shaped intranuclear inclusions in
      the case with the progranulin mutation and FTLD tauopathy with predominance of 4R
      tau in the remaining two, both with the P301L mutation. CONCLUSIONS: Our results
      are similar to those of the great European series. FTLD must be suspected in
      presenile patients with prominent behavioral and/or language disorders.
      Neuroimaging supports the diagnosis in the majority of cases. The huge
      sociofamiliar impact of FTLD, presenile onset, high frequency of familial history
      of dementia and possibility of genetic study and counseling highlight its
      clinical relevance.

PMID- 18802800
TI  - [Acute disseminated encephalomyelitis: study of factors involved in a possible
      development towards multiple sclerosis].
AB  - Acute disseminated encephalomyelitis (ADEM) is an uncommon disease characterized
      by inflammation and demyelination of the central nervous system (CNS). It
      typically occurs after a viral infection or vaccination and is more frequent in
      children. Its immediate and longterm prognosis is expected to be good (20% of
      cases with sequelae). Although ADEM is typically monophasic, occasional relapses
      may occur. Differential diagnosis, mostly in the early phases, is established
      with multiple sclerosis (MS), a chronic inflammatory demyelinating disease of the
      CNS that may have worse prognosis. Traditionally it has been believed that 10% of
      ADEM patients develop MS. However, this percentage could be higher according to
      several recently published clinical series. Some clinical and paraclinical
      patterns are considered to confer risk of developing MS when present in ADEM
      patients. Our study has aimed to: a) describe a series of 29 patients (22
      children and 9 adults) admitted in our hospital and diagnosed of ADEM between
      1990 and 2005; b) study those patients considered to have risk patterns of
      developing MS, and c) compare the child and adult populations of our series.
      After a median 55 month follow-up, 6 children (27%) and no adults developed MS.
      In our series, risk patterns for developing MS predicted conversion to MS more
      accurately in children than in adults. Eight patients (6 children and 2 adults)
      had sequelae, cognitive in 6 of them. Our work supports that also observed in
      recent publications: that both conversion to MS or presence of sequelae after an
      episode of ADEM are more frequent than traditionally considered.

PMID- 18802801
TI  - Determinants of the structure of resistance-sized arteries in hypertensive
      patients.
AB  - OBJECTIVE: It has been previously demonstrated that structural alterations of
      subcutaneous small resistance arteries of hypertensive patients, as indicated by
      an increased media to lumen (M/L) ratio, is the most potent predictor of
      cardiovascular events. The aim of the present study was to identify possible
      determinants of small resistance artery structure that may be evaluated with non
      invasive approaches. MATERIALS AND METHODS: One hundred and ninety-nine subjects
      (normotensives, essential hypertensives and patients with secondary hypertension)
      were included in the present study. All subjects were submitted to a biopsy of
      subcutaneous fat from the gluteal or the anterior abdominal region. Small
      resistance arteries were dissected and mounted on an isometric myograph, and M/L
      ratio was measured. All patients underwent standard biochemical tests, clinic
      blood pressure measurement, standard echocardiography and 24-h ambulatory blood
      pressure measurement. Glomerular filtration rate (GFR) was calculated according
      to MDRD study formula and Cockroft's formula. RESULTS: Significant correlation
      was found between M/L ratio and, respectively: GFR calculated both with MDRD
      study formula and Cockroft-Gault formula, creatinine serum, blood urea nitrogen,
      glycaemia, circulating sodium, clinical pulse pressure, stroke volume to pulse
      pressure ratio, clinical systolic, diastolic and mean arterial pressure, daytime
      pulse pressure. However, in a multivariate regression analysis, only serum
      creatinine remained in the model, and proved to be an independent predictor of
      small artery structure. CONCLUSIONS: Indices of renal function and, probably, of
      large artery distensibility may be related to small arteries remodelling in
      hypertension.

PMID- 18802802
TI  - Association of Inhalation Toxicologists (AIT) working party recommendation for
      standard delivered dose calculation and expression in non-clinical aerosol
      inhalation toxicology studies with pharmaceuticals.
AB  - There are many ways in which the dose can be expressed in inhalation toxicology
      studies. This can lead to confusion when comparing results from studies performed
      in different laboratories. A working party of the Association of Inhalation
      Toxicologists has reviewed this subject in detail and has collected data from 10
      inhalation laboratories and used these data to determine a new algorithm for the
      calculation of Respiratory Minute Volume (RMV), one of the most important factors
      in the calculation of delivered dose. The recommendations of the working party
      for regulatory inhalation toxicology studies with pharmaceuticals are as follows:
      1. The dose should be reported as the delivered dose calculated according to the
      formula: DD = C x RMV x D(xIF)/BW, where DD = delivered dose (mg/Kg); C =
      concentration of substance in air (mg/L); RMV =respiratory minute volume or the
      volume of air inhaled in one minute (L/min); D = duration of exposure (min); IF =
      proportion by weight of particles that are inhalable by the test species, the
      inhalable fraction (inclusion of this parameter is not essential provided that
      the aerosol has reasonable respirability for the intended species. If it is
      included, the way in which it is determined should be clearly stated); BW =
      bodyweight (Kg). 2. The RMV for mice, rats, dogs and cynomolgus monkeys should be
      calculated according to the formula:RMV(L/min) = 0.608 x BW(Kg)(0.852). 3. If
      deposited dose or the amount of material actually retained inthe respiratory
      tract is presented as supplementary information,the way in which it is calculated
      should be clearly stated.4. Dose should always be presented in mg/Kg but may also
      bepresented in other ways, such as mg/unit body surface area, as supplementary
      information.

PMID- 18802804
TI  - Central executive involvement in children's spatial memory.
AB  - Previous research with adults found that spatial short-term and working memory
      tasks impose similar demands on executive resources. We administered spatial
      short-term and working memory tasks to 8- and 11-year-olds in three separate
      experiments. In Experiments 1 and 2 an executive suppression task (random number
      generation) was found to impair performances on a short-term memory task (Corsi
      blocks), a working memory task (letter rotation), and a spatial visualisation
      task (paper folding). In Experiment 3 an articulatory suppression task only
      impaired performance on the working memory task. These results suggest that short
      term and working memory performances are dependent on executive resources. The
      degree to which the short-term memory task was dependent on executive resources
      was expected to be related to the amount of experience children have had with
      such tasks. Yet we found no significant age-related suppression effects. This was
      attributed to differences in employment of cognitive strategies by the older
      children.

PMID- 18802805
TI  - Cortisol, depression, somatization and treatment choice.

PMID- 18802807
TI  - Osteoprotegerin/RANKL system imbalance in active polyarticular-onset juvenile
      idiopathic arthritis: a bone damage biomarker?
AB  - OBJECTIVE: To evaluate the importance of receptor activator of nuclear factor
      kappaB (RANK)/receptor activator of nuclear factor kappaB ligand
      (RANKL)/osteoprotegerin (OPG) modulation in active polyarticular juvenile
      idiopathic arthritis (pJIA) patients with and without bone erosions. METHODS:
      Thirty female patients (mean age 11.07+/-3.77 years, range 4-17 years) with
      active pJIA and 30 healthy gender- and age-matched controls were consecutively
      selected for this study. All involved articulations were assessed by X-ray and
      examined for the presence of bone erosions. The serum levels of RANKL and OPG
      were measured using an enzyme-linked immunosorbent assay (ELISA). RESULTS:
      Patients with active pJIA had higher levels of serum RANKL than controls [2.90
      (0.1-37.4) vs. 0.25 (0.1-5.7) pg/mL, p = 0.007] and a lower OPG/RANKL ratio
      [21.25 (1.8-897.6) vs. 347.5 (9-947.8), p = 0.005]. However, levels of OPG were
      comparable in both groups [55.24 (28.34-89.76) vs. 64.42 (30.68-111.28) pg/mL, p
      = 0.255]. Higher levels of serum RANKL and a lower OPG/RANKL ratio were also
      observed in active pJIA patients with bone erosions compared to controls [3.49
      (0.1-37.4) vs. 0.25 (0.1-5.7) pg/mL, p = 0.0115 and 14.3 (1.8-897.6) vs. 347.5 (9
      947.8), p = 0.016]. However, RANKL levels and OPG/RANKL ratio were similar in
      pJIA patients without bone erosion and controls [1.75 (0.1-10.9) vs. 0.25 (0.1
      5.7) pg/mL, p = 0.055 and 29.2 (3.3-756.8) vs. 347.5 (9-947.8), p = 0.281].
      CONCLUSION: These data suggest that active pJIA with bone erosions is associated
      with high serum levels of RANKL and a low OPG/RANKL ratio, indicating that these
      alterations may reflect bone damage in this disease.

PMID- 18802808
TI  - Prevention of skin cancer in primary healthcare: an evaluation of three different
      prevention effort levels and the applicability of a phototest.
AB  - BACKGROUND/OBJECTIVE: The high skin cancer incidence in western society, and its
      known association with sun exposure habits, makes the area an important target
      for prevention. We investigated, in a primary healthcare setting, differentiated
      levels of prevention efforts directed at the propensity of the patient to change
      his/her sun habits, sun protection behaviour, and attitudes, after information
      intervention. Additionally, the impact of the performance of a phototest to
      determine individual sun sensitivity was evaluated. METHODS: 308 patients
      visiting a primary healthcare centre in southern Sweden completed a questionnaire
      concerning sun habits, sun protection behaviour, and attitudes, and were
      randomized into one of three groups, representing increasing levels of prevention
      effort in terms of resources. Feedback on their questionnaire and general
      preventive sun protection advice was given, in the first group by means of a
      letter, and in the second and third groups by a doctor's consultation. Group 3
      also underwent a phototest, with a self-reading assessment and a written follow
      up of the phototest result. Change of sun habits, behaviour, and attitudes, based
      on the Transtheoretical Model of Behaviour Change and on Likert scale scorings,
      was evaluated after 6 months, by a repeated questionnaire. RESULTS: Prevention
      mediated by a doctor's consultation had a clearly better impact on the subjects.
      The addition of a phototest did not further reinforce this effect in the group as
      a whole, but it did for a subgroup of individuals with high ultraviolet (UV)
      sensitivity, as determined by the phototest itself, suggesting that this might
      actually be a tool to improve outcome in this high-risk group. CONCLUSION: A
      personal doctor's consultation is a valuable tool in the effective delivery of
      preventive information in the general practice setting. In individuals with high
      UV-sensitivity and thus high risk for skin cancer the performance of a photo-test
      reinforces a positive outcome in habits, behaviour and attitudes.

PMID- 18802809
TI  - Meeting report of European ALS Consortium (EALSC): 6th European ALS congress
      research workshop and young investigators' meeting.
AB  - The 6th European ALS congress took place in Lisbon, Portugal from 20 to 22 June.
      The scientific sessions focused on disease pathogenesis and neuroprotection
      including genetics, proteomics, metabolomics and various disease models. In the
      clinical session the latest findings on nutrition, ventilation, psychological
      support as well as new developments in the field of imaging and neurophysiology
      were discussed. This review outlines the work that was presented during the
      meeting.

PMID- 18802810
TI  - Isolation of Mycoplasma bovis from broiler chickens in Turkey.
AB  - Mycoplasma bovis normally affects cattle, in which it causes pneumonia in calves,
      mastitis, arthritis and other diseases. In the present article we report the
      isolation of this bovine pathogen from the tracheas of broiler chickens with no
      clinical signs. The most probable source of infection was the cattle herd sharing
      the farm with the chickens.

PMID- 18802811
TI  - Symmetric cyanine dyes for detecting nucleic acids.
AB  - A novel approach to the design of sensitive fluorescent probes for nucleic acids
      detection is proposed. Suitable modifications of tri- and pentamethine cyanine
      dyes in the polymethine chain and/or in the heterocyclic residues can result in a
      significant decrease in unbound dye fluorescence intensity and an increase in dye
      emission intensity in the presence of DNA compared to the unsubstituted dye. The
      sharp enhancement in the fluorescence intensity upon dye interaction with double
      stranded DNA permits the application of the modified tri- and pentamethine dyes
      as fluorescent probes in double-stranded DNA detection in homogeneous assays.

PMID- 18802812
TI  - Safranine fluorescent staining of wood cell walls.
AB  - Safranine is an azo dye commonly used for plant microscopy, especially as a stain
      for lignified tissues such as xylem. Safranine fluorescently labels the wood cell
      wall, producing green/yellow fluorescence in the secondary cell wall and
      red/orange fluorescence in the middle lamella (ML) region. We examined the
      fluorescence behavior of safranine under blue light excitation using a variety of
      wood- and fiber-based samples of known composition to interpret the observed
      color differentiation of different cell wall types. We also examined the basis
      for the differences in fluorescence emission using spectral confocal microscopy
      to examine lignin-rich and cellulose-rich cell walls including reaction wood and
      decayed wood compared to normal wood. Our results indicate that lignin-rich cell
      walls, such as the ML of tracheids, the secondary wall of compression wood
      tracheids, and wood decayed by brown rot, tend to fluoresce red or orange, while
      cellulose-rich cell walls such as resin canals, wood decayed by white rot, cotton
      fibers and the G-layer of tension wood fibers, tend to fluoresce green/yellow.
      This variation in fluorescence emission seems to be due to factors including an
      emission shift toward red wavelengths combined with dye quenching at shorter
      wavelengths in regions with high lignin content. Safranine fluorescence provides
      a useful way to differentiate lignin-rich and cellulose-rich cell walls without
      counterstaining as required for bright field microscopy.

PMID- 18802813
TI  - Modification of Luna's technique for staining eosinophils in the hamster cheek
      pouch.
AB  - The cheek pouch is an anatomical peculiarity of hamsters, widely used as an
      experimental model for oral cancer, and characterization of its normal cell
      populations and the changes they undergo in pathological conditions is of great
      interest. Our studies of epithelium-connective tissue interactions have revealed
      that hamster eosinophils are not easily recognizable because they are small and
      exhibit a larger nucleus:cytoplasm ratio than those in human and other animal
      tissues. Luna's technique is the most popular specific staining technique for
      eosinophils. Owing to the morphology of hamster eosinophils, however, it was
      necessary to modify Luna's technique to stain these cells selectively against a
      more contrasting background that would enable their identification and
      quantitation in the hamster cheek pouch. The modification involved staining the
      sections with a solution of 0.5% Biebrich scarlet in lithium carbonate followed
      by counterstaining with 1% metanil yellow in water. The eosinophils were stained
      selectively red against a yellow background. Our technique avoided nuclear
      staining and enhanced observation of selectively stained granules in a scarce
      cytoplasm with a contrasting background, which permits fast, reproducible studies
      and automated image analysis.

PMID- 18802814
TI  - Falling is not just for older women: support for pre-emptive prevention
      intervention before 60.
AB  - OBJECTIVE: This study aimed to report falls and identify factors that might
      predict a fall in women aged between 40 and 80 years and thus provide evidence of
      earlier falls and need for morbidity preventive intervention. DESIGN AND
      PARTICIPANTS: A prospective cohort study design over 5 years. Personal
      demographic data of age, co-morbidities, number of prescribed medications, falls,
      activity level and living situation were obtained at face-to-face interview.
      Height, weight, body mass index and postural stability were measured in
      participating women living independently in the community. RESULTS: Women were
      categorized into age decade cohorts, with 463 remaining at the year 5 assessment.
      At baseline, 8% of the women in their forties, 14% in their fifties, 25% in their
      sixties and 40% in their seventies had fallen in the previous 12 months. Over the
      5-year study period, 21% of women in their forties and fifties, 31% of women in
      their sixties and 47% in their seventies had fallen. Multiple fallers mostly
      comprised women in their sixties and seventies. Parametric modeling and the
      classification tree approach revealed age and number of co-morbidities to be most
      predictive of a fall. Women < 60 years old had an increased risk of a fall by 8%
      and women > 60 years an increased risk of a fall by 35% with every additional co
      morbidity. Stability and other demographics were not predictive of falling.
      CONCLUSIONS: For women over 40 years old, the number of co-morbidities increased
      the risk of a fall. The falls risk escalated with additional co-morbidities if
      they were over 60 years. Preventive program participation to maintain good health
      beginning by the forties appears vital to prevent falls.

PMID- 18802815
TI  - The menopause symptom profile of Maori and non-Maori women in New Zealand.
AB  - OBJECTIVES: To describe menopause symptoms in postmenopausal Maori and non-Maori
      New Zealand women, and explore relationships between symptoms, sociodemographic
      profile and hormone replacement therapy (HRT) use. METHODS: Cross-sectional
      analysis of data collected during recruitment of women from 27 primary-care
      practices into an observational study and the international WISDOM trial of
      postmenopausal HRT. RESULTS: A total of 3616 women aged 49-70 years (mean 58.9
      years) were recruited between 1999 and 2004. Maori and non-Maori participants
      differed in demographic and clinical characteristics, but few differences were
      observed in the frequency of menopause-related symptoms. Vasomotor symptoms (hot
      flushes and/or night sweats) were reported by 34.4% of women, with no
      statistically significant difference between Maori and non-Maori (controlling for
      demographic variables, p > 0.05). Compared to non-Maori, Maori were less likely
      to have ever used HRT (24% vs. 54%), and only 5% of Maori reported current HRT
      use compared to 30% of non-Maori (p < 0.05). CONCLUSIONS: Maori and non-Maori
      have the same rate of self-reported vasomotor symptoms despite differences in
      factors thought to influence the experience of menopause symptoms. Differences in
      HRT use between Maori and non-Maori need to be further explored to identify
      contributing factors and whether, in turn, these factors impact on quality of
      life.

PMID- 18802816
TI  - Immunotoxicity of perfluorooctanoic acid and perfluorooctane sulfonate and the
      role of peroxisome proliferator-activated receptor alpha.
AB  - Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) are
      environmentally widespread and persistent chemicals with multiple toxicities
      reported in experimental animals and humans. These compounds can trigger
      biological activity by activating the alpha isotype of peroxisome proliferator
      activated receptors (PPARs), ligand-activated transcription factors that regulate
      gene expression; however, some biological effects may occur independently of the
      receptor. Activation of the peroxisome proliferator-activated receptor alpha
      (PPARalpha) modulates lipid and glucose homeostasis, cell proliferation and
      differentiation, and inflammation. Reported immunomodulation in experimental
      animals exposed to PFOA and PFOS has included altered inflammatory responses,
      production of cytokines and other proteins, reduced lymphoid organ weights, and
      altered antibody synthesis. Mounting experimental animal evidence suggests
      PPARalpha independence of some immune effects. This evidence originates primarily
      from studies with PPARalpha knockout models exposed to PFOA that demonstrate
      hepatic peroxisome proliferation, reduced lymphoid organ weights, and altered
      antibody synthesis. As human PPARalpha expression is significantly less than that
      of rodents, potential PPARalpha independence indicates that future research must
      explore mechanisms of action of these compounds, including PPARalpha-dependent
      and -independent pathways. This multiauthored review contains brief descriptions
      of current and recently published work exploring immunomodulation by PFOA and
      PFOS, as well as a short overview of other PPARalpha ligands of therapeutic and
      environmental interest.

PMID- 18802817
TI  - Cardiovascular and eye activity measures as indices for momentary changes in
      mental effort during simulated flight.
AB  - This study examines effects of momentary changes in mental effort on
      cardiovascular and eye activity measures. A total of 19 male pilots performed an
      instrument flight task. Task load was manipulated by having the pilots perform
      flight manoeuvres of varying complexity. Multilevel analyses demonstrated clear
      effects of momentary changes in mental effort on both the cardiovascular and the
      eye activity measures. An increase in task load resulted in an increase of heart
      rate and a decrease in heart rate variability, mean dwell time and fixation
      duration. Heart rate differentiated between resting period and task execution.
      Heart rate variability from short data segments provided more insight in
      intermediate levels of mental effort. The eye activity measures were sensitive to
      intermediate levels of mental effort as well. Attitude changes resulted in an
      increase of mean dwell time and mean fixation duration. Task analysis is required
      to use eye measures as valid indices of mental effort. Having indications of the
      effects of changing mental demands during daily work of operators is of great
      importance nowadays. This paper presents an approach to estimate such effects on
      the basis of heart rate and eye activity measures. In particular, the use of
      averaged short-term heart rate variability measures is a relatively new aspect.

PMID- 18802818
TI  - The effect of sonification display pulse rate and reliability on operator trust
      and perceived workload during a simulated patient monitoring task.
AB  - The present study investigated the effects of sonification pulse rate and sensor
      reliability on operator trust and mental workload. Processing resources and
      operator trust were sensitive to both pulse rate and sensor reliability. These
      findings suggest that setting pulse rates to 60 pulses per min may have
      considerable benefits in critical task environments.

PMID- 18802819
TI  - Computer- vs. paper-based tasks: are they equivalent?
AB  - In 1992, Dillon published his critical review of the empirical literature on
      reading from paper vs. screen. However, the debate concerning the equivalence of
      computer- and paper-based tasks continues, especially with the growing interest
      in online assessment. The current paper reviews the literature over the last 15
      years and contrasts the results of these more recent studies with Dillon's
      findings. It is concluded that total equivalence is not possible to achieve,
      although developments in computer technology, more sophisticated comparative
      measures and more positive user attitudes have resulted in a continuing move
      towards achieving this goal. Many paper-based tasks used for assessment or
      evaluation have been transferred directly onto computers with little regard for
      any implications. This paper considers equivalence issues between the media by
      reviewing performance measures. While equivalence seems impossible, the
      importance of any differences appears specific to the task and required outcomes.

PMID- 18802820
TI  - Comfort evaluation of maternity support garments in a wear trial.
AB  - This study aims to evaluate the wear comfort of eight commercially available
      maternity support garments. The thermophysiological, sensory/tactile and movement
      comfort were assessed in a wear trial using a 19-item questionnaire. Fourteen
      pregnant Chinese women aged 32.3 +/- 4.2 years were recruited from a local
      obstetric clinic. The results show that the tested garments generally provided
      greater sensory comfort than thermophysiological comfort. The thermophysiological
      comfort was mainly influenced by the fibre contents and breathability.
      Significant linear relationships were found between material appearance and hand
      feel (r = 0.86, p < 0.001), and between non-itchiness and no red mark (r = 0.78,
      p < 0.001). Movement comfort was influenced by the garment type and style
      features. Overall, the soft, good-fit, cotton/elastane maternity brief was
      perceived as the best product. The findings of comfort needs in pregnant women
      and the effects of various garment attributes would be helpful for the
      development of maternity support garment design criteria that are required to
      satisfy critical ergonomic needs. Low back pain during pregnancy is a common and
      significant health problem. A maternity support garment is regarded as a
      convenient and safe device to stabilise the lumbar spine so as to relieve pain.
      However, patient compliance is likely to be affected by discomfort and
      inconvenience. The results of this study provide guidance for the optimal design
      of maternity support clothing.

PMID- 18802821
TI  - An ergonomic comparison of firearm safety mechanisms.
AB  - As with most machines, the integral safety mechanism on firearms is vital to
      injury or fatality free operation. Presently, there is little or no
      standardisation in the design of these mechanisms. In this investigation, five
      existing designs found on both military and commercial rifles were evaluated
      ergonomically to determine the most effective characteristics for incorporation
      into future designs. The designs were evaluated experimentally on ease of use,
      visual effectiveness and operational impact. Three groups, representing a total
      of 30 subjects with widely varying experience, were selected. Results strongly
      suggest that safeties whose actuators are mounted within easy reach of the
      trigger finger are preferred and have the least operational impact. Subjects also
      preferred and were more adept at recognising safety status when the indicator was
      located on the receiver/barrel along the normal line of sight. Subjects more
      often correctly identified safety status when the indicator utilised colouring,
      was clearly marked and/or was in the normal line of sight. The results of this
      research prove that ergonomics can contribute to the understanding of firearm
      safety dynamics. The two essential components of safety mechanism design
      identified in this investigation, unambiguous status visibility and impact-free
      operation, are also likely to have implications in non-firearm safety mechanism
      design. This is particularly true for devices whose inadvertent operation can
      cause injury, as well as systems in which operational effectiveness can be
      jeopardised when attentiveness or operational control are lost in the process of
      actuating a poorly designed safety mechanism.

PMID- 18802822
TI  - Metabolic demands of simulated firefighting tasks.
AB  - Firefighters having higher cardiovascular fitness completed a series of simulated
      firefighting tasks more quickly than those having lower fitness. These results
      support the need of a high level of cardiovascular fitness for firefighters to
      ensure not only their safety, but that of fellow firefighters and rescue victims.

PMID- 18802823
TI  - Effect of ship motion on spinal loading during manual lifting.
AB  - This study investigated the effects of ship motion on peak spinal loading during
      lifting. All measurements were done on a ship at sea. In 1-min trials, which were
      repeated over a wide range of sailing conditions, subjects lifted an 18 kg box
      five times. Ship motion, whole body kinematics, ground reaction forces and
      electromyography were measured and the effect of ship motion on peak spinal
      moments and compression forces was investigated. To investigate whether people
      time their lifts in order to reduce the effect of ship motion on back loading,
      trials were performed at a free and at a constrained (lifting every 10s) work
      pace. With increase of the (local) vertical ship acceleration, increased moments
      and compression forces were found. Furthermore, lifting at a free work pace did
      not result in smaller effects of ship motion on spinal moments and compression
      forces than working at a constrained work pace.

PMID- 18802824
TI  - Effect of object width on precision grip force and finger posture.
AB  - This study aimed to define the effect of object width on spontaneous grasp.
      Participants held objects of various masses (0.75 to 2.25 kg) and widths (3.5 to
      9.5 cm) between thumb and index finger. Grip force, maximal grip force and
      corresponding finger postures were recorded using an embedded force sensor and an
      optoelectronic system, respectively. Results showed that index finger joints
      varied to accommodate the object width, whereas thumb posture remained constant
      across conditions. For a given object mass, grip force increased as a function of
      object width, although this result is not dictated by the laws of mechanics.
      Because maximal grip force also increased with object width, we hypothesise that
      participants maintain a constant ratio between grip force and their maximal grip
      force at each given width. Altogether we conclude that when the task consists in
      manipulating objects/tools, the optimal width is different than when maximal
      force exertions are required.

PMID- 18802829
TI  - SHPIMS.

PMID- 18802832
TI  - SnapAnatomy, a computer-based interactive tool for independent learning of human
      anatomy.
AB  - Computer-aided instruction materials are becoming increasing popular in medical
      education and particularly in the teaching of human anatomy. This paper describes
      SnapAnatomy, a new interactive program that the authors designed for independent
      learning of anatomy. SnapAnatomy is primarily tailored for the beginner student
      to encourage the learning of anatomy by developing a three-dimensional
      visualization of human structure that is essential to applications in clinical
      practice and the understanding of function. The program allows the student to
      take apart and to accurately put together body components in an interactive, self
      paced and variable manner to achieve the learning outcome.

PMID- 18802833
TI  - Digital infrared and ultraviolet imaging part 2: ultraviolet.
AB  - The authors reviewed and tested a range of equipment for their use in undertaking
      infrared (IR) and ultraviolet (UV) imaging in the digital workflow. In Part 1 the
      authors reported their findings with respect to undertaking IR imaging. Part 2
      covers direct UV and UV fluorescence imaging.

PMID- 18802834
TI  - Fujifilm Finepix IS-Pro: a review.
AB  - As part of a series of investigations into the utility of digital SLR cameras for
      IR and UV photography, the authors tested a Fujifilm Finepix IS-Pro DSLR camera
      using the previously reported test procedures.

PMID- 18802844
TI  - Design, development and optimization of a novel time and pH-dependent colon
      targeted drug delivery system.
AB  - The aim of present study was to develop a time- and pH-dependent system for
      delivering mesalamine to the colon. The system consists of the core tablet of
      mesalamine which is compression coated with hydroxypropyl methylcellulose (HPMC
      K4M) (time-dependent factor). This is then coated with pH-dependent polymer
      Eudragit L100. The simplex lattice design was adopted to optimize the independent
      variables i.e. amount of HPMC (X1), dextrose (X2) and polyvinyl pyrollidone (PVP)
      (X3) and to study their effect on the dependent variables i.e. lag time and time
      for 50% drug dissolution (t50). The results of the linear interactive model and
      graphical representation revealed that as the amount of HPMC increases, the lag
      time and t50 value also increases and as the amount of dextrose and PVP were
      increased the lag time and t50 value decreases.

PMID- 18802843
TI  - Modeling structural adaptation of microcirculation.
AB  - The functional properties of microcirculation crucially depend on its
      angioarchitecture, (i.e., vessel arrangement and morphology). The
      microcirculation is subject to continuous dynamic structural adaptation (i.e.,
      remodeling) controlled by hemodynamic and metabolic stimuli. Due to the
      complexity of the interactions among stimuli, reactions, and functional
      properties, an adequate understanding of structural adaptation requires
      mathematical models in addition to experimental investigations. Mathematical
      models have been developed that allow the prediction of realistic vascular
      properties, based on generic patterns of vascular responses. These models can be
      used to investigate and predict distributions of vessel morphology consistent
      with certain putative adaptation principles of terminal vascular beds in response
      to local hemodynamic and metabolic conditions. They have suggested new
      hypotheses, including the importance of conducted responses in network
      adaptation, and can explain the mechanisms underlying observed structural and
      functional network properties. In the future, the value of such models can be
      enhanced by including the effects of longitudinal stretch and pulsatility, the
      relationship between acute tone and structural adaptation, and the description of
      molecular and cellular mechanisms underlying structural responses of
      microvessels.

PMID- 18802845
TI  - Preparation of multiparticulate vaginal tablet using glyceryl monooleate for
      sustained progesterone delivery.
AB  - Most of the sustained release vaginal formulations are in the form of bioadhesive
      gels and tablets. Though proved efficient, their presence in the vagina for a
      longer time as a bulk produces discomfort and interference with body functioning
      including sexual activities. Hence, they lack complete patient compliance. In
      this study, multiparticulate vaginal tablets were prepared by utilizing
      progesterone (PRO) loaded dry powder precursor of cubic phase (DPPCP) of glyceryl
      monooleate (GMO). DPPCP were obtained by spray drying GMO with magnesium
      trisilicate (MTS) and have presented PRO sustained release in simulated vaginal
      fluid (SVF) for 14 hours. The effect of hydrophilic and hydrophobic tableting
      excipients on compression, phase, bioadhesion and drug release properties of
      prepared tablets was evaluated. The effervescent hydrophilic tablet (EHT)
      prepared with hydrophilic excipients showed rapid disintegration but, diminished
      sustaining ability owing to transformation into lamellar phase whereas the
      multiparticulate hydrophobic tablet (MHT) obtained from hydrophobic excipients
      presented both rapid disintegration and sustained release in SVF by virtue of
      cubic phase retention. During bioadhesivity testing, fast disintegration of MHT
      with formation of uniform and viscous bioadhesive layer on cow mucosa was
      observed even with a small volume of SVF. As MHT may not produce discomfort and
      interference, it will be preferred over bioadhesive gel or tablet.

PMID- 18802846
TI  - The green revolution in bioethics.

PMID- 18802849
TI  - Ethics, pandemics, and the duty to treat.
AB  - Numerous grounds have been offered for the view that healthcare workers have a
      duty to treat, including expressed consent, implied consent, special training,
      reciprocity (also called the social contract view), and professional oaths and
      codes. Quite often, however, these grounds are simply asserted without being
      adequately defended or without the defenses being critically evaluated. This
      essay aims to help remedy that problem by providing a critical examination of the
      strengths and weaknesses of each of these five grounds for asserting that
      healthcare workers have a duty to treat, especially as that duty would arise in
      the context of an infectious disease pandemic. Ultimately, it argues that none of
      the defenses is currently sufficient to ground the kind of duty that would be
      needed in a pandemic. It concludes by sketching some practical recommendations in
      that regard.

PMID- 18802850
TI  - Carrots and sticks: keeping healthcare workers on the job in a public health
      disaster.

PMID- 18802851
TI  - Health care workers' willingness to work in a pandemic.

PMID- 18802852
TI  - Suppose they gave an epidemic and nobody came?

PMID- 18802853
TI  - Not in my job description.

PMID- 18802854
TI  - Specifying the duty to treat.

PMID- 18802855
TI  - Ethics and epidemics.

PMID- 18802856
TI  - A duty to treat during a pandemic? The time for talk is now.

PMID- 18802857
TI  - The duty to care in a pandemic.

PMID- 18802858
TI  - Without consent: moral imperatives, special abilities, and the duty to treat.

PMID- 18802859
TI  - Public health and duties to the population during a pandemic.

PMID- 18802860
TI  - Remembering the "pan" in "pandemic": considering the impact of global resource
      disparity on a duty to treat.

PMID- 18802861
TI  - Healthcare professionals and the reciprocal duty to treat during a pandemic
      disaster.

PMID- 18802862
TI  - Pandemic influenza and the duty to treat: the importance of solidarity and
      loyalty.

PMID- 18802863
TI  - Ethical implications of implantable radiofrequency identification (RFID) tags in
      humans.
AB  - This article reviews the use of implantable radiofrequency identification (RFID)
      tags in humans, focusing on the VeriChip (VeriChip Corporation, Delray Beach, FL)
      and the associated VeriMed patient identification system. In addition, various
      nonmedical applications for implanted RFID tags in humans have been proposed. The
      technology offers important health and nonhealth benefits, but raises ethical
      concerns, including privacy and the potential for coercive implantation of RFID
      tags in individuals. A national discussion is needed to identify the limits of
      acceptable use of implantable RFID tags in humans before their use becomes
      widespread and it becomes too late to prevent misuse of this useful but ethically
      problematic technology.

PMID- 18802864
TI  - Ethics and indemnification regarding the VeriChip.

PMID- 18802865
TI  - Implantable tags: don't close the door for aunt Millie!

PMID- 18802866
TI  - Implantable radiofrequency identification (RFID) tags are not tattoos.

PMID- 18802867
TI  - Who is buying bioethics research?
AB  - Growing ties to private industry have prompted many to question the impartiality
      of academic bioethicists who receive financial support from for-profit
      corporations in exchange for ethics-related services and research. To the extent
      that corporate sponsors may view bioethics as little more than a way to
      strengthen public relations or avoid potential controversy, close ties to
      industry may pose serious threats to professional independence. New sources of
      support from private industry may also divert bioethicists from pursuing topics
      of greater social importance, such as the needs of medically underserved
      communities. To inform ongoing debates about the financing of bioethics and its
      transparency to those concerned about potential sources of bias, we examined
      funding disclosures appearing in original research reports in major bioethics
      journals. Reviewing research published over a 15-year period, we found little
      evidence that for-profit corporations are influencing bioethics research
      directly. Instead, we found evidence that a great number of organizations, both
      public and private, support bioethics research. These findings suggest that
      worries about the cooption of bioethics research by a few interested stakeholders
      are greatly overstated and undersupported by available data.

PMID- 18802868
TI  - In search of a measure of industry funding.

PMID- 18802869
TI  - Hidden sources of private industry funding.

PMID- 18802870
TI  - Who is buying normative bioethics research?

PMID- 18802871
TI  - 'Tell us what you want to do, and we'll tell you how to do it ethically'-
      academic bioethics: routinely ideological and occasionally corrupt.

PMID- 18802872
TI  - Does money make bioethics go 'round?

PMID- 18802875
TI  - PEGylation of somatropin (recombinant human growth hormone): impact on its
      clearance in humans.
AB  - 1. PHA-794428 is a PEGylated version of somatropin (human growth hormone). The
      pharmacokinetics of PHA-794428 have been studied in humans following single
      subcutaneous administration (dose range 10-500 microg kg(-1)). In the same study
      the pharmacokinetics of somatropin were also determined following a 3.6 mg (51
      microg kg(-1)) subcutaneous dose. Comparison of the pharmacokinetics of both
      molecules indicates that PEGylation of somatropin with a 40 kD PEG results in a
      ten- to 20-fold increase in area under the curve and a similar increase in half
      life when compared with somatropin in human (at equivalent subcutaneous doses).
      2. Literature data indicate that somotropin is cleared by two mechanisms. The
      first processes is clearance by glomerular filtration. This is a passive, non
      capacity-limited process. A second, capacity-limited, process is mediated by
      interaction with growth hormone receptors present in a number of tissues
      including the liver. It is hypothesized that PHA-794428 shares the same clearance
      mechanisms. However, the addition of the PEG moiety has modulated the clearance
      by both of these processes. Pharmacokinetic modelling of human serum
      concentration data obtained for these molecules strongly supports this
      hypothesis. The renal clearance is reduced due to the increased size of the
      molecule (Cl/F reduced from 9.6 to 0.1 l h(-1) for somatropin and PHA-794428,
      respectively). In addition, the reduction in growth hormone receptor affinity has
      reduced the clearance mediated by interaction with this receptor (somatropin Km =
      3.6 microg l(-1) and Vmax = 104 microg h(-1)/PHA-794428 Km = 53 microg l(-1) and
      Vmax = 84 microg h(-1)).

PMID- 18802876
TI  - [Nephrogenic systemic fibrosis].
AB  - Nephrogenic systemic fibrosis (NSF) is a novel disease entity, increasingly
      diagnosed over the last years in patients with renal functional impairment and
      chronic kidney disease. Recently, gadolinium-containing MR contrast agents have
      been causally associated with the development NSF. Herein, we present the case of
      a dialysis-dependent young patient with systemic lupus erythematodes, who
      developed disabling cutaneous sclerosis of extremities, abdomen and mammae.
      Clinical and laboratory investigations revealed no signs of activity of the
      underlying disease. Histopathological examination of a skin biopsy was consistent
      with NSF showing profound thickening of tissue septae with mucine deposition and
      slight fibroblast proliferation without inflammatory reaction. Analysis of the
      patient's medical history revealed that she had undergone repeated contrast
      enhanced MR scans, including MR angiographies with high doses of gadopentetate.
      UV phototherapy was little effective, and not until kidney transplantation two
      years later with good allograft function, improvement of clinical symptoms was
      observed. Discussion of this case summarizes the current knowledge of clinical
      features and pathogeneses of NSF, including the role of gadolinium-containing
      contrast agents. Evolving clinical implications are summarized in the current
      Tubingen University Hospital guideline for the use of contrast-enhanced MR scans
      in patients with impaired renal function.

PMID- 18802877
TI  - [Are compulsory admissions more frequent in immigrants and ethnic minorities?].
AB  - OBJECTIVE: To assess the frequency of compulsory admissions to psychiatric
      hospitals in immigrants and members of ethnic minorities compared to German
      patients. METHODS: The rates and quotas of compulsory admissions were assessed in
      the city of Frankfurt / Main during one year (2005). The data were compared to
      the epidemiological data of the inhabitants of the catchment area of the clinic
      (control group). RESULTS: The findings show a lower rate of admission to the
      psychiatric hospital in immigrants and members of ethnic minorities. The QUOTA of
      compulsory admissions compared to the total rate of admissions to the psychiatric
      hospital was higher in immigrants and members of ethnic minorities. The RATE of
      compulsory admissions out of 100 000 population in immigrants and members of
      ethnic minorities was similar to the rate of compulsory admissions in German
      population. CONCLUSIONS: Although some methodological limitations exist the
      findings are in line with results from other European and non-European countries.

PMID- 18802878
TI  - [Turner-syndrome and psychosis: a case report and brief review of the
      literature].
AB  - OBJECTIVE: Turner syndrome encompasses several chromosomal abnormalities and
      includes a typical clinical manifestation. While common somatic symptoms are
      often described, neuropsychiatric alterations are rare and not frequently
      mentioned in the literature. METHOD: In this paper, we report on a subject with
      Turner syndrome who also showed psychotic symptoms. CONCLUSIONS: The theoretical
      background and the relevance of this observation are discussed. Furthermore, this
      article briefly reviews existing reports on Turner syndrome and psychosis and
      presents neuropsychiatric changes in patients with Turner syndrome.

PMID- 18802879
TI  - First clinical application of a navigation-controlled shaver in paranasal sinus
      surgery.
AB  - Conventional, pointer-based navigated Functional Endoscopic Sinus Surgery (FESS)
      has been shown to have certain limitations: necessity of instrument change for
      navigation, changes in the surgeon's line-of-sight axis, and limited length of
      use of the navigation information. These limitations result in negative
      consequences regarding the surgeon's attentiveness in any given situation, as
      well as in his cognitive work-load. The principle of Navigated Control offers
      advantages concerning these problems and limitations of the conventionally
      navigated FESS. This Chapter analyzes the first clinical deployment of a
      navigation-controlled shaver in FESS on the basis of the following questions: (1)
      Is clinical deployment of the navigation-controlled shaver possible with the pre
      clinic evaluated set-up? (2) What information relevant to the surgery is relayed
      in an intraoperative setting by the navigation-controlled shaver? (3) How does
      deployment of the navigation-controlled shaver affect the ergonomics of the
      surgery? Ten patients with chronic sinusitis ethmoidalis were included in the
      study (average age: 48 [22-71], m:w=4:6). The preoperative and intraoperative
      workflow was documented according to the Innovation Center Computer Assisted
      Surgery (ICCAS) Workflow protocol. Data regarding the surgical validity of the
      information and ergonomic characteristics were recorded by means of
      questionnaires. The average time required for segmentation of the workspace was
      14.2 minutes. The shaver switched off through Navigated Control an average 16.5
      times during an FESS. From this amount, five shutdowns on average were initiative
      and six were determined to be provoked. The shutdowns were indicated by the
      operators to be correct in 199 of 220 (90.5%) events and in agreement with the
      actual position and planned resection borders. The quality of the relayed
      navigation information was indicated with an average Level of Quality (LOQ) of
      56.4 [50-80]. The most favorable evaluation was attained for navigation in the
      area of the sphenoid sinus with 71 points on average [60-80]. During an FESS, the
      navigation information led to a change in the planned surgical strategy an
      average of 0.9 [0-3] times. Throughout all surgical procedures, the situation
      awareness was assessed an average of 2.7 points better than with the
      conventionally navigated FESS. This also was the case for the cognitive workload
      (Workload shift) with 2.8 [1-3.5] points. This Chapter proves the clinical
      applicability of a navigation-controlled instrument by means of a shaver in Ears,
      Nose, and Throat (ENT) surgery for the first time. Reproduction of the dental
      splint registration, manual segmentation of the working space, and attachment of
      the registration star still prove to be critical aspects. Data regarding quality
      of the information relayed by the navigation system and resulting change in
      surgical strategy lead to the conclusion that the authors are dealing with, in
      the overall evaluation, supplementary and surgically relevant information. This
      information is more efficiently transferred to the surgeon by means of Navigated
      Control that allows, according to the following results, both an improved
      understanding of the information and cognitive easing of stress for the surgeon.

PMID- 18802880
TI  - Face validity study of the ProMIS augmented reality laparoscopic suturing
      simulator.
AB  - To prevent unnecessary mistakes and avoidable complications in laparoscopic
      surgery, there has to be proper training. A safe way to train surgeons for
      laparoscopy is simulation. This study addresses the face validity of ProMIS, an
      Augmented Reality laparoscopic simulator, as a tool for training suturing skills
      in laparoscopic surgery. A two-paged, 12-item structured questionnaire, using a
      five-point-Likert scale, was presented to 50 surgeons/surgical interns. The
      participants were allotted to two groups: an "expert" (>50 procedures; N=23) and
      a referent group (<50 procedures; N=27). Non-parametric statistics were used to
      determine statistical differences. General consensus existed in both expert and
      referent groups, delineating ProMIS as a useful tool in teaching suturing skills
      surgeons/surgical interns (mean + or - st dev, resp, score 4.91 + or - 0.42 and
      4.93 + or - 0.38) with regard to realism, tactile feedback, and suturing
      techniques. Significant differences in opinion regarding the ergonomics and
      design of ProMIS between the expert and referent groups existed. The ProMIS
      Augmented Reality laparoscopic simulator is regarded as a useful tool in
      laparoscopic training in both expert and referent groups. Although significant
      differences in opinion existed with regards to ergonomics and design of ProMIS,
      they were present between experts and novices.

PMID- 18802881
TI  - Effectiveness of LigaSure diathermy coagulation in liver surgery.
AB  - The principal cause of perioperative morbidity and mortality following hepatic
      resection is excessive intraoperative hemorrhage. This study evaluates the
      operative use of the LigaSure device in sealing ductal structures during major
      and minor hepatic resections. Patients were analyzed between June 1994 and
      December 2005, comparing 89 randomly selected cases undergoing hepatic resections
      using the clamp-crushing technique with LigaSure electrocautery and hepatic
      inflow occlusion where appropriate with 70 patients undergoing various hepatic
      resections using the clamp-crushing technique alone with hepatic inflow occlusion
      where appropriate. Intraoperative blood loss and perioperative blood transfusion
      requirements were significantly less for patients in the LigaSure group. LigaSure
      assisted hepatic resection was generally performed more quickly than the
      conventional clamp-crushing technique. The overall maximum postoperative AST,
      ALT, and bilirubin serum levels were similar in the two groups, as was the
      incidence of major postoperative complications. The LigaSure device in this
      randomized study is safe and simple to use, resulting in less perioperative blood
      loss and transfusion requirement during hepatic parenchymal transection.

PMID- 18802882
TI  - Prevention and treatment of surgical thrombosis and thromboembolism.
AB  - Surgical, post-surgical deep vein thrombosis (DVT), or thromboembolism is common
      and potentially catastrophic. Surgical DVT may lead to either immediate post
      surgical morbidity or long-term morbidity by way of post-phlebitic syndrome and
      chronic venous insufficiency. In addition, surgery-associated pulmonary embolism
      (PE) may lead to significant morbidity or post-surgical mortality. As this
      surgical complication is so common, both the North American Consensus Conference
      Committee, sponsored by the American College of Chest Physicians, and the
      International Consensus Conference Committee, sponsored by the International
      Society of Angiology, have convened periodically during the past two decades to
      analyze the highest-quality published studies and publish clear standards and
      guidelines for prevention and treatment of surgical DVT and thromboembolism. The
      latest North American Recommendations were published in 2004 and the latest
      International Committee recommendations were released in 2006. These
      recommendations are summarized in this chapter, which offers the clinician the
      latest guidelines for prevention and treatment of surgery-associated DVT and
      thromboembolism.

PMID- 18802883
TI  - SILVER versus other antimicrobial dressings: best practices!
AB  - All chronic wounds are colonized by bacteria. Increased bacterial burden or
      critical colonization can be deleterious to wound healing. In view of the
      ubiquitous presence of microbes, the clinician must discern whether bacterial
      balance (contamination or colonization) or bacterial damage has occurred. Silver
      is a common topical agent used to combat bacterial burden in chronic wounds.
      Given the wide array of silver-related wound care products, it is difficult to
      determine which product should be used. By reviewing relevant scientific
      evidence, we propose an acronym SILVER to address the key contentious issues.
      These issues are summarized as SILVER: Signs of bacterial damage, the need for
      Ionic silver, Log reduction of bacteria, Vehicle (importance of moisture
      balance), Effect on normal cells, and Bacterial Resistance.

PMID- 18802884
TI  - Comprehensive management for venous stasis ulcers.
AB  - Traditional treatment of venous stasis ulceration has focused on compression
      therapy, debridement, and topical wound management. Prospective randomized
      studies have shown that only two additional treatment modalities are effective in
      healing venous ulceration: pentoxyphylline and bilayered living-cell therapy.
      Although initial healing rates of up to 75% can be accomplished, there is an
      unacceptably high recurrence rate that is thought to be due to patient
      noncompliance. However, recurrence of venous stasis ulceration is more likely
      secondary to uncorrected venous hypertension, a disease whose causes have been
      largely ignored in wound treatment. Few previous studies show improved healing
      rates of ulcers after surgical correction of venous hypertension with saphenous
      stripping. Venous pathology responsible for venous hypertension can now be easily
      corrected with new minimally invasive techniques. The purpose of this chapter is
      to define venous hypertension in patients with ulceration, and provide evidence
      that surgical treatment to eliminate venous hypertension combined with evidence
      based treatment strategies will not only improve short-term outcomes but will
      also prevent recurrent ulceration.

PMID- 18802885
TI  - Current management of venous ulcers: an evidence-based review.
AB  - Chronic venous ulceration is a common and important medical problem that causes
      significant morbidity. Venous ulcers are expensive to treat, have substantial
      economic effects in terms of days of work lost, and adversely impact the
      patient's quality of life. Relying on evidence allows for a rationale of clinical
      decision making. The objectives of venous ulcer management include the healing of
      the ulcer, prevention of recurrence, and improvement of edema. Compression is the
      cornerstone of venous ulcer therapy. Adjunctive modalities such as surgery,
      growth factors, grafting, biologic skin substitutes, dressings, and oral
      medication have differing levels of evidence supporting their use, and may also
      facilitate the healing process.

PMID- 18802886
TI  - Healing diabetic foot ulcers using cortical bone fenestration and cell therapy.
AB  - Chronic wounds with exposed bone present a challenge for clinicians. Without
      intact periosteum, cortical bone is relatively avascular and provides a poor base
      for wound healing and skin grafting. It has been shown that cortical bone
      fenestration and decortication can expedite wound healing in exposed calvarial
      bone. We present a case study where cortical bone fenestration and the subsequent
      application of human skin equivalent were used to heal a chronic wound of the
      lower extremity. We propose that this technique can facilitate the production of
      granulation tissue, and can aid the healing of chronic wounds of the lower
      extremities associated with exposed bone.

PMID- 18802887
TI  - Biological basis of diabetic foot wounds.
AB  - The steps to achieving a healthy healing wound include a correct diagnosis,
      ensuring a good local blood supply, debriding the wound to reveal a clean base,
      correcting the biomechanical abnormality, and nurturing the wound until it shows
      signs of healing. Debridement should be performed as often as necessary until the
      wound is deemed clean and ready for reconstruction. The repair is then dictated
      by how much of the foot remains post-debridement and how the foot can be closed
      in the most biomechanically stable construct possible. The subsequent
      reconstruction can then usually be accomplished by simple techniques most of the
      time, and with complex flap reconstruction in about 10% of cases. Wound healing
      adjuncts such as growth factor, cultured skin, and hyperbaric oxygen can be
      helpful adjuncts.

PMID- 18802888
TI  - Creative limb-salvage surgical and endovascular revascularization strategies in
      treating critical limb ischemia.
AB  - Critical limb ischemia (CLI) is implicated in cases of between 220,000 to 240,000
      amputations in the United States and Europe annually. Over the last five years,
      great technical strides have been made in both the surgical and nonsurgical
      endovascular treatments of CLI. This chapter analyzes and highlights those
      creative limb salvage strategies now used to treat CLI and save limbs.

PMID- 18802889
TI  - Role of keratinocytes in healing of chronic wounds.
AB  - Keratinocytes are the major cellular component of epidermis, and they have
      several critical roles in the wound healing process. They are involved in the
      intricate mechanisms of initiation, maintenance, and completion of wound healing.
      The properties of keratinocytes vary depending upon their location and
      circumstances within chronic wounds. Keratinocytes at the non-healing edges of
      chronic wounds differ from normal, healthy keratinocytes. The cross-talk between
      healthy keratinocytes and other cell types participating in wound healing is
      critical for successful wound closure. This discovery provides the biological
      foundation for debridement: Removing "bad" cells from a quiescent wound edge and
      exposing or even replacing them with "healthy" cells with a high regenerative
      potential can enhance epithelialization and healing of chronic wounds. This paper
      will review the biological and pathological properties of keratinocytes as they
      relate to wound healing, and the ways in which they may provide highly
      efficacious therapy for patients with chronic wounds.

PMID- 18802890
TI  - Evidence-based rationale for offloading treatment modalities.
AB  - Diabetic foot ulcers (DFU) are a common co-morbidity affecting patients with
      diabetes. A variety of factors, including diabetic peripheral neuropathy, altered
      gait, and increased pressure on certain regions of the foot, can over time result
      in a diabetic foot wound. Reducing pressure at the site of the ulcer can promote
      healing and prevent further ulceration. Offloading is an evidence-based treatment
      modality for patients with DFUs and is part of the standard protocol for
      treatment. We discuss here the most common offloading modalities, placing them in
      the context of relevant medical and compliance issues that affect their use and
      success.

PMID- 18802891
TI  - Cut-and-screw insertion: a method for safe and speedy secondary trocar insertion
      in laparoscopic surgery.
AB  - Laparoscopic surgery is increasingly applied to the treatment of gastrointestinal
      disease. However, the insertion of secondary trocars following pneumoperitoneum
      carries the risk of serious complications such as major vascular and bowel
      injuries. Such injury can arise when the force required for the trocar insertion
      is such that it causes the operator to have impaired control over the entry.
      There is a need for a procedure of secondary trocar insertion that is safe and
      easy to perform for training clinicians in laparoscopic surgery. We have
      developed the "cut-and-screw" insertion method for secondary trocar insertion
      using a specially developed laparoscopic cannula with a sharp edge and housing.
      Our procedure is simple, rapid, and safe. In this chapter, we describe the
      technique and present our initial clinical results.

PMID- 18802892
TI  - Capsule endoscopy for detection of small bowel malignancies.
AB  - Capsule Endoscopy (CE) is a recent diagnostic tool for detection of small bowel
      disease. The tiny imaging capsule has to be swallowed by the patient, which
      allows transmission by radiofrequency two images each second, to sensors worn
      around the patient's abdomen. After eight hours, the pictures can be downloaded
      and read by a Gastroenterologist. CE allows for exploration of the entire small
      bowel mucosa, which involves segments not accessible by classical endoscopy.
      Moreover, it is the only technique that involves a visualization of the entire
      small bowel without sedation. Tumors of the small intestine are rather infrequent
      and could account for approximately 2% of gastrointestinal neoplasms. As symptoms
      of small bowel tumors are not specific, most published series include patients
      with bleeding or anemia of undetermined origin, the main indication for
      performing CE. Currently, no doubt exists of the ability regarding the CE to
      increase the diagnostic yield of small bowel tumors, or to alter their management
      and improve their outcome in the absence of metastases. Overall, tumors along the
      small intestine are located by CE in 2.5%-8.9% of patients who undergo this
      procedure. While being an evident improvement, CE has some limitations, such as
      the inability to treat lesions locally or take tissue specimens. This last point
      is an important shortcoming, because small bowel tumors can be malignant
      (approximately 2/3 of the cases) or benign. The future of CE is bright, and
      special capsule devices already exist to specifically explore the esophagus as
      well as the large intestine.

PMID- 18802893
TI  - An update of available innovative staple line reinforcement materials in
      colorectal surgery.
AB  - Despite refinements in the field of gastrointestinal surgical stapling,
      anastomotic leakage and bleeding still remain a serious problem associated with
      substantial morbidity and mortality. To prevent or reduce these complications, a
      diversity of staple line reinforcement techniques have been developed. The
      available literature from 1977 through 2007 was reviewed to find relevant data
      about innovative colorectal staple line reinforcement techniques. Many different
      forms of staple line reinforcement are available. Reinforcement methods can be
      material applied exogenously to the staple line or incorporated into the staple
      line. Reinforcement materials can be nonabsorbable, semi-absorbable, or fully
      absorbable. Gastrointestinal staple line reinforcement is well known, but it is a
      relatively new method for colorectal surgery. Staple line reinforcement is an
      effective technique in reducing complications in stapled anastomoses only if
      proper buttressing material is used. Absorbable material seems to have several
      advantages over non- or semi-absorbable staple line reinforcement. New and
      promising techniques are fibrin glue, C-seal, and biosynthesized absorbable
      cellulose used as staple line reinforcement material. Unfortunately, there is not
      much experience reported with these new materials, thus further investigation is
      needed.

PMID- 18802894
TI  - Anorectal sepsis and fistula-in-ano.
AB  - Anorectal abscesses and fistulas are common maladies that are usually readily
      diagnosed and effectively treated. However, complex fistulous disease challenges
      even the most expert of surgical specialists. The management options in this
      subset of patients are suboptimal, with treatment often requiring multiple
      procedures, putting the patient at risk for continued symptoms and fecal
      incontinence. In this chapter, the clinical aspects of perianal suppurative
      disease are discussed and an attempt is made to deal with many of the more
      challenging aspects of patient management.

PMID- 18802895
TI  - The advantage of Kakita's method with pancreaticojejunal anastomosis for
      pancreatic resection.
AB  - In 1996, we reported the technical aspects of our new method for end-to-side
      pancreatojejunostomy (Kakita's method) that we performed in combination with the
      Whipple procedure without any complications related to failure in the
      anastomosis. In this chapter, we will introduce our technique in end-to-end style
      pancreatojejunal anastomosis with fewer anastomotic complications. The purpose of
      this study was to review Kakita's method with pancreatoduodenectomy. From April
      1990 to December 2005, 324 consecutive cases of pancreatoduodenectomy were
      performed in the Department of Surgery at Kitasato University. In our institute,
      reconstruction in pancreatoduodenectomy is basically performed according to a
      modified Child's procedure. Our method is simple and can be applied wherever an
      end-to-side pancreatojejunal anastomosis is required. It consists of three steps:
      First, a drainage tube is inserted into the pancreatic duct. The second step,
      which is the unique aspect of our method, is an attachment of the jejunal wall
      and the cut surface of the pancreas using a single-layer suture technique. This
      allows us not only to reduce the number of sutures but also to eliminate some of
      the complicated manipulations required by other methods. The jejunal wall fully
      covers the cut surface of the pancreas, leaving no uncovered area between the
      wall and the pancreas. Third, a direct anastomosis between the pancreatic duct
      and the mucosal layer of the jejunal loop is applied. In our series,
      pancreatojejunal anastomotic leakage occurred only in 4 out of 324 patients,
      which was 1.23%. All patients were successfully treated with conservative therapy
      using drainage for an extended period postoperatively. The newly devised
      pancreatojejunostomy in our department is a simple, safe, and reliable procedure
      with excellent results.

PMID- 18802896
TI  - Fecal incontinence: an update on available techniques in diagnosis and treatment.
AB  - Fecal incontinence remains a major problem with significant social and medical
      implications. Its causes are diverse and not always apparent. Therefore,
      diagnostic workup is essential to find the underlying cause and initiate adequate
      treatment. Treatment options include conservative interventions and surgical
      procedures. To improve the diagnosis and treatment of patients suffering from
      fecal incontinence, an update and overview of available techniques can be
      helpful. This chapter includes indications and complications in conservative and
      surgical treatment. It also includes flowcharts for everyday practice.

PMID- 18802897
TI  - Mid-term results of robot-assisted laparoscopic repair of large hiatal hernia: a
      symptomatic and radiological prospective cohort study.
AB  - Studies reporting on the recurrence rate after laparoscopic repair of large
      hiatal hernias (HH), including anatomical asymptomatic recurrence, are scarce.
      This prospective cohort study evaluated the symptomatic and objective outcome of
      robot-assisted laparoscopic HH repair up to more than 1 year after surgery. A
      prospective cohort study was performed on 40 consecutive patients with emphasis
      on operating times, blood loss, intra- and postoperative complications,
      symptomatic outcome, and anatomical recurrence rate at a minimum of 1 year after
      surgery. Robot-assisted laparoscopic HH repair proved to be an effective
      technique with a relatively low mid-term recurrence rate in this prospective
      series. The operating team experienced the support of the robotic system as
      beneficial, especially in the dissection of the hernia sac and extensive crural
      repair.

PMID- 18802898
TI  - Site-specific rectocele repair with dermal graft augmentation: comparison of
      porcine dermal xenograft (Pelvicol) and human dermal allograft.
AB  - This study is a retrospective chart review comparing 195 women who underwent
      rectocele repair with either a porcine dermal xenograft or human allogenic
      cadaveric dermal graft augmentation over a two year period. A site-specific
      defect repair was completed prior to augmentation with the graft. Examinations
      were performed preoperatively and postoperatively using the pelvic organ prolapse
      quantification system. Questionnaires were used to assess constipation and
      dyspareunia. De novo dyspareunia and cure rates for constipation and dyspareunia
      were not statistically different between the two groups. Site-specific fascial
      rectocele repairs with xenograft or allograft augmentation were found to have
      similar complication rates as well as objective and subjective cure rates.

PMID- 18802899
TI  - Use of circular stapler for laparoscopic excision of rectosigmoid anterior wall
      endometriosis.
AB  - The objective of this study was to assess the feasibility and safety of
      laparoscopic rectosigmoid anterior wall discoid resection for endometriosis using
      the circular stapler. A retrospective analysis was conducted of nine consecutive
      patients undergoing laparoscopic radical excision of pelvic endometriosis,
      including bowel anterior wall discoid excision, at the Fertility and Pelvic
      Surgery Clinic and private hospitals in Sao Paulo, Brazil. The selected
      intervention was a radical laparoscopic endometriosis resection, including
      rectosigmoid anterior wall excision with the circular stapler. For certain types
      of bowel endometriosis, the anterior wall discoid stapler excision proved a
      suitable option that diminishes the chances of serious complications such as
      bowel fistula or anastomosis dehiscence.

PMID- 18802900
TI  - Using a laparoscope manipulator (LAPMAN) in laparoscopic gynecological surgery.
AB  - The LAPMAN (Medsys, Gembloux, BELGIUM) is a dynamic laparoscope holder guided by
      a joystick clipped onto the laparoscopic instruments under the index finger of
      the operator. It confers optimal control of the visual field while operating,
      ensures stable and smooth displacement of the laparoscope, and allows the
      operator to work in conditions of restricted surgical assistance, due to either
      unavailability of staff or economic constraints. It has been tested successfully
      in pilot studies in laparoscopic gynecologic surgery.

PMID- 18802901
TI  - A long-survived case with solitary splenic metastasis from ovarian carcinoma.
AB  - A61-year-old postmenopausal woman with ovarian carcinoma was treated with two
      surgical operations and a series of platinum-based chemotherapy. A solitary
      metastasis into the splenic parenchyma was identified 33 months after the second
      surgery by abdominal computed tomography with an increased serum level of CA-125.
      She underwent a pancreaticosplenectomy and received platinum-based adjuvant
      chemotherapy continuously for 2 years. Her serum CA-125 level decreased to a
      normal range and she has lived without any recurrence for more than 10 years
      after the splenectomy. Solitary metastases from ovarian cancer into the splenic
      parenchyma are extremely rare. Among 18 cases previously reported, this present
      case shows the longest disease-free survival. Because these cases show favorable
      prognosis after splenectomy, surgical treatment should be considered along with
      adjuvant chemotherapy.

PMID- 18802902
TI  - Laparoscopic sacral colpopexy.
AB  - Sacral colpopexy is the gold standard for vaginal vault suspension throughout the
      literature. The operation is considered to be invasive yet very effective. The
      laparoscopic approach to the sacral colpopexy is not only effective but can have
      minimal morbidity in the correct surgeon's hands. The authors have performed more
      than 500 sacral colpopexy via laparoscopy with minimal morbidity and thus share
      their technique with the reader.

PMID- 18802903
TI  - Dermoid tumors of the ovary: evaluation of the gasless lift-laparoscopic
      approach.
AB  - Laparoscopic removal is widely accepted as the treatment of choice for dermoid
      tumors. However, the spillage of dermoid content with the laparoscopic approach
      is very high compared to laparotomy. The potential malignancy of dermoid tumors
      and the rare, but difficult to treat, chemical peritonitis in cases of spillage
      of dermoid content should lead to an adaptation of procedures during an
      endoscopic operation on a dermoid tumor to comply with the precautions of the
      "open" technique. Lift-laparoscopy combines laparoscopy with the standard
      procedures of laparotomy and thus may help reduce the spillage of dermoid
      contents. In a retrospective study of 108 patients with dermoid tumors, the
      frequency of the rupture of a dermoid tumor during a lift-laparoscopic operation
      was examined. Among the 79 cases of organ-preserving treatment, there were only
      three cases (3.8%) where a rupture of the dermoid capsule occurred. Even in cases
      of ruptures, it was possible to avoid spillage by closing the lesion with a clamp
      and continue the enucleation of the dermoid tumor during a lift-laparascopic
      operation. After thorough abdominal cavity lavage, none of these three cases
      showed a cytological contamination of the abdominal cavity with dermoid cells.
      None of the ovariectomy or adnexectomy cases showed a rupture. Histologically,
      there was also no carcinoma in any of the examined dermoid tumors. By adapting
      the endoscopic dermoid surgery to the precautions established in an open surgery
      technique using gasless lift-laparoscopy, ruptures and cell spilling can be
      avoided to a large extent but not completely excluded. Compared with other
      methods, the number of ruptures and spillage of dermoids by organ-preserving
      treatment as well as ovariectomy is lowest using a lift-laparoscopic procedure.

PMID- 18802904
TI  - The role of vessel sealing technologies in laparoscopic surgery.
AB  - With the advent of new technology, it is crucial to understand the mechanics of
      how instruments work to fully be able to utilize them and prevent injury. One of
      the cornerstones which makes laparoscopy possible is the use of vessel sealing
      instruments. Cutting, coagulation, and dissection are some paramount qualities of
      vessel sealing instruments; however, knowledge of the type of energy being used
      on tissue is of utmost importance. The various forms of energy vessel sealing
      instruments have advantages and disadvantages depending on the task. In the
      following text, monopolar, bipolar, and ultrasonic vessel sealing instruments for
      laparoscopic surgery are discussed at length. From how these instruments work to
      their cost, a detailed look at the available and most widely used laparoscopic
      vessel sealing instruments is reviewed. The accompanying illustrations are to aid
      in recognition and understanding of their use.

PMID- 18802905
TI  - Valsalva graft in the Bentall procedure: from mechanical valve to the
      BioValsalva, world's first biological aortic conduit.
AB  - Aortic root replacement is the procedure of choice for patients with ascending
      aortic aneurysms and diseased aortic valve leaflets. The increasing age of
      patients who undergo aortic root surgery, and data that support the use of a
      biological aortic valve in the younger population, have significantly increased
      the need for a composite biological valved conduit. The third-generation
      Triplextrade (Terumo Vascutek, Renfrewshire, Scotland, UK) Dacron conduit with
      its three-layer technology, can be stored in glutaraldehyde along with biological
      prostheses while maintaining a complete blood impermeability. As the result of
      this fundamental improvement, the ready-to-use composite biological valved graft
      is currently available for the first time in different sizes, which avoids the
      need of assembling it on the surgical table. The procedure is expedited and a
      better hemostasis achieved because of the intrinsic characteristics of the new
      three-layered conduit. The BioValsalva (Terumo Vascutek, Renfrewshire, Scotland,
      UK) has been obtained by suturing a stentless aortic valve (Elan, Kohler, Leeds,
      UK) inside a Triplex Valsalva graft and combining the advantages of a biological
      valved conduit with the advantages of better leaflets dynamics, less tension on
      coronary ostia, and improved coronary flow proper of the Valsalva conduit. The
      authors' preliminary clinical experience with the BioValsalva is reported herein
      and the technique is discussed.

PMID- 18802906
TI  - Medium-term results of surgical ventricular restoration with papillary muscle
      realignment: providing additional benefits in enlarged ischemic left ventricle.
AB  - In 2001, we described a new surgical technique of surgical ventricular
      restoration (SVR) in severe heart failure by papillary muscle re-alignment and
      volume reduction. This procedure has been offered in our institution to patients
      with severely impaired left ventricular function. Here we examine our mid-term
      results and also compare them with a similar cohort of patients who had coronary
      artery bypass grafting (CABG) only. Between 1998 and 2005, 30 patients underwent
      SVR by papillary muscle realignment with coronary artery revascularization at our
      institution. A subset of 20 patients had their left ventricular volume measured
      by echocardiogram and MRI scan, and a maximal cardiopulmonary exercise test was
      performed before and after the operation. An unselected consecutive cohort of
      patients with matching age, gender, and hemodynamic status who underwent CABG
      only without SVR was tested using the same protocol and the results were
      compared. We noticed that there was a significant advantage for patients who had
      additional SVR over patients who had CABG only. The observed improvement in those
      who had SVR may be due to reduced metabolic mismatch as a result of reduced wall
      tension and normalization of the apical twist of the left ventricle. We believe
      this would provide a form of surgical treatment for heart failure secondary to
      ischemic cardiomyopathy at a time of reduced donor organ availability for
      transplant.

PMID- 18802907
TI  - Completely endoscopic microwave ablation of atrial fibrillation on the beating
      heart using bilateral thoracoscopy.
AB  - The pharmacological treatment of atrial fibrillation (AF) has proven to be wholly
      inadequate. Although highly successful, the surgical approach is too invasive and
      has not been widely adopted. Progress has been made with breathtaking speed over
      the last decade toward the creation of an ablative surgical procedure that
      retains a high cure rate yet solves the problem of invasiveness. This chapter
      will describe a procedure that uses microwave energy delivered via a thin, long,
      and flexible catheter through endoscopic ports to treat AF. As energy delivery
      methods, surgical techniques, and assessment procedures continue to improve,
      treatments such as this one will hopefully attract the largest number of patients
      who suffer with this arrhythmia to seek a safe and effective cure.

PMID- 18802908
TI  - Evaluation of the accuracy of three CT-free surgical navigation systems in total
      knee arthroplasty (TKA) using a coordinate measuring machine.
AB  - Previous studies have shown that the accuracy of computer-assisted surgery (CAS)
      via computed tomography (CT) free systems is useful when applied in the clinical
      realm. However, few studies have compared CAS systems to the current gold
      standard, manually applied measuring guides. Thirty total knee arthroplasties
      (TKA) were performed on artificial Sawbones knees using three different
      navigational systems. The TKAs were performed by a fellowship-trained joint
      reconstruction surgeon as well as a third- and a fourth-year orthopedic resident
      to assess differences in performance with regard to surgical experience. Using a
      two-way multivariate analysis of variance (MANOVA), no statistical differences
      were found in the accuracy of each of the three CAS navigational systems.
      Similarly, no differences were found between the accuracy of CAS systems and the
      gold standard measuring method. No differences in performance were found between
      the orthopedic residents and the fellowship-trained surgeon, suggesting a
      relatively small learning curve and usability. Definitive assessment of the
      clinical efficacy should be further assessed in a cadaveric study or, ideally, by
      way of a randomized clinical trial.

PMID- 18802909
TI  - Strategies to reduce blood loss during posterior spinal fusion for neuromuscular
      scoliosis: a review of current techniques and experience with a unique bipolar
      electrocautery device.
AB  - In this chapter, we review current techniques employed to decrease blood loss and
      describe the effective use of a unique bipolar electrocautery device in a patient
      with neuromuscular scoliosis undergoing posterior spinal fusion (PSF). The
      reduction of blood loss and subsequent elimination of allogeneic blood
      transfusion is a desired outcome in all surgeries and is a major concern during
      PSF. In the child or adolescent with neuromuscular scoliosis, this becomes a
      greater concern due to a variety of factors such as the inability of the
      musculature to compress blood vessels, extensive surgical exposure, and the
      duration of the operation. A multitude of pharmacological, anesthetic, and
      surgical techniques-including preoperative autologous blood donation and human
      recombinant erythropoietin, intraoperative blood salvage techniques, and topical
      and systemic hemostatic agents-are employed to reduce the need for transfusion.
      Many of these techniques carry their own risks and, thus far, a systematic
      approach has not been established to decrease the need for transfusion. In the
      continued pursuit of reducing intraoperative blood loss, other surgical
      techniques must be developed.

PMID- 18802910
TI  - Midflexion instability in revision total knee arthroplasty.
AB  - Midflexion instability is a new concept associated with revision total knee
      arthroplasty. It appears as rotational instability with combined external
      rotation and valgus stress in a knee flexed between 45 degrees and 90 degrees.
      Three main factors contribute to this instability: anterior medial collateral
      ligament attenuation, femoral-tibial articular geometry, and tibial post-femoral
      box geometry. Rotational stress should be included when assessing stability
      intraoperatively to identify those patients who may require additional
      constraint.

PMID- 18802911
TI  - A comparison of the minimally invasive dual-incision versus posterolateral
      approach in total hip arthroplasty.
AB  - This study directly compared a minimally invasive dual-incision muscle-sparing
      surgical technique with a standard posterolateral approach in total hip
      arthroplasty to assess for early complications, clinical success, and alignment.
      Total hip arthroplasties using a minimally invasive, muscle-sparing, dual
      incision approach were performed on 21 hips (20 patients). This cohort was
      compared to a contemporaneously performed group of 21 hips (20 patients) using a
      standard posterolateral approach. Five complications were reported for the dual
      incision group versus one complication for the posterolateral group.
      Postoperative radiographic alignment of the prosthesis was closer to optimal for
      the posterolateral group. The dual-incision group had longer operating times and
      a significant increase in complications. The authors have discontinued the use of
      this technique based on the results of this study.

PMID- 18802912
TI  - Minimally invasive therapeutic interventional procedures in the spine: an
      evidence-based review.
AB  - This chapter evaluates the current evidence on common minimally invasive
      therapeutic spinal procedures based on the Levels of Evidence and Grades of
      Recommendation developed by the Centre for Evidence-Based Medicine (Oxford,
      United Kingdom). The results of the evaluation of current clinical evidence allow
      the following recommendations to be made: epidural adhesiolysis performed
      repeatedly every 3 months to 4 months is effective in the "post lumbar
      laminectomy" syndrome; epidural steroid injections may provide only short-term
      relief from pain in lumbar radiculopathy but have no long-term effect; selective
      nerve root injections of corticosteroids have no therapeutic effect on the long
      term natural history of radiculopathy symptoms; intra-articular facet joint
      injections of corticosteroids have no therapeutic effect on lower back pain
      (grade of recommendation: A). Furthermore, percutaneous vertebroplasty and
      balloon kyphoplasty provide immediate pain relief from osteoporotic spinal
      fractures but no significant long-lasting benefit (grade of recommendation: B).
      Finally, there is limited evidence (grade of recommendation: C) of the value of
      medial branch (facet) neurotomy, sacroiliac joint injection of steroids, and
      intradiscal electrothermal therapy, as well as of the advantages of percutaneous
      endoscopic lumbar discectomy over open microdiscectomy. As the level of evidence
      is generally low, more prospective randomized-controlled studies are needed to
      establish the value of the considered methods.

PMID- 18802913
TI  - Endoscopic assisted microdecompression of cervical disc and foramen.
AB  - The anterior endoscopic cervical microdecompression (AECM) of disc and foramen
      with added application of nonablative lower holmium laser energy for disc
      shrinkage (laser thermodiskoplasty) has proven to be safe, less traumatic,
      easier, and more efficacious than conventional methods with significant economic
      savings. It preserves spinal motion and provides a channel for spinal
      arthroplasty. It is an effective alternative or replacement for conventional open
      cervical spinal surgery for discectomy, and can decompress spinal stenosis and
      degenerative spine conditions.

PMID- 18802914
TI  - Perioperative complications of minimally invasive surgery (MIS): comparison of
      MIS and open interbody fusion techniques.
AB  - The risk of perioperative complications while adopting minimally invasive spine
      surgery techniques may slow the acceptance of this technology. We assess the
      perioperative complication rate with minimally invasive single- and two-level
      interbody fusions and compare this incidence with a contemporaneous cohort of
      open single- and two-level open interbody fusions, with all procedures completed
      by a single surgeon in a single practice group. We compiled all open and MIS
      interbody fusion cases completed during the study period. Sofamor-Danek X-Tube
      and Stryker Luxor minimally invasive systems were used on all patients. Medical
      records were reviewed to assess any adverse events occurring in the perioperative
      period. Care was taken to include all medical and surgical adverse events and
      complications occurring within 30 days of surgery. Over the study period, 28
      minimally invasive lumbar fusions were identified: 24 single- and 4 two-level
      cases. Both TLIF and PLIF techniques were used. This cohort was compared with a
      group of 19 single- and two-level open interbody fusion cases completed over the
      same period. The complication rate for the MIS cohort was 18%, with 7
      complications occurring in 5 patients. In the open group, 8 complications
      occurred in 7 patients, an incidence of 37%. A standard distribution of
      complications occurred, and the difference between the two groups was not
      statistically significant. Limiting our analysis to severe complications yielded
      rates of 7% and 21% for the two groups, also not significantly divergent.
      Perioperative complications are not more common in well-selected MIS patients.
      Allowing for proper patient selection, MIS techniques have a favorable
      complication profile.

PMID- 18802915
TI  - Restoration of function in complete spinal cord injury using peripheral nerve
      rerouting: a summary of procedures.
AB  - Until relatively recently, few procedures have been developed that restore
      significant motor and sensory function in individuals with obsolete (ie,
      chronic), complete spinal cord injury (SCI). Building upon the methodology used
      to treat brachial root avulsion, the authors have developed peripheral nerve
      rerouting procedures that have restored some function in hundreds of patients
      with such SCI. Many of the treated patients have regained life-enhancing function
      depending upon their injury level, such as walking with assistive devices,
      partial hand function, urination, sexual sensation, etc. Although sophisticated
      surgeries, the basic concept is theoretically simple: a functional nerve from
      above the injury site is rerouted and connected to a paralysis-affected
      peripheral nerve below the injury site. This Chapter summarizes more than a dozen
      rerouting procedures, which restore function that range from breathing to toe
      sensation. This summary discusses the indications and criteria for choosing the
      best donor nerve based on the specific injury level, and emphasizes major
      procedural features such as the use of selected interfascicular anastomosis,
      modified end-to-side suture techniques, vascularized donor nerves, a muscle
      trigger for the synchronized contraction of congenerous muscles, and
      reconstruction procedures to restore donor-nerve function.

PMID- 18802916
TI  - Interaction trap/two-hybrid system to identify interacting proteins.
AB  - The parameters and experimental conditions for this important system are
      constantly undergoing improvement. This newest version includes expanded tables
      describing interaction trap components and additional libraries compatible with
      the interaction trap system. It also features a new protocol on performing a hunt
      by interaction mating. Some of the commercial vendors selling yeast two-hybrid
      reagents recommend using interaction mating to perform a hunt, so this procedure
      should be of great interest.

PMID- 18802918
TI  - Focus on HTR2C: A possible suggestion for genetic studies of complex disorders.
AB  - HTR2C is one of the most relevant and investigated serotonin receptors. Its role
      in important brain structures such as the midbrain, the lateral septal complex,
      the hypothalamus, the olfactory bulb, the pons, the choroid plexus, the nucleus
      pallidus, the striatum and the amygdala, the nucleus accumbens and the anterior
      cingulated gyrus candidate it as a promising target for genetic association
      studies. The biological relevance of these brain structures is reviewed by way of
      the focus on HTR2C activity, with a special attention paid to psychiatric
      disorders. Evidence from the genetic association studies that dealt with HTR2C is
      reviewed and discussed alongside the findings derived from the neuronatmic
      investigations. The reasons for the discrepancies between these two sets of
      reports are discussed. As a result, HTR2C is shown to play a pivotal role in many
      different psychiatric behaviors or psychiatric related disrupted molecular
      balances, nevertheless, genetic association studies brought inconsistent results
      so far. The most replicated association involve the feeding behavior and
      antipsychotic induced side effects, both weight gain and motor related: Cys23Ser
      (rs6318) and -759C/T (rs3813929) report the most consistent results. The lack of
      association found in other independent studies dampens the clinical impact of
      these reports. Here, we report a possible explanation for discrepant findings
      that is poorly or not at all usually considered, that is that HTR2C may exert
      different or even opposite activities in the brain depending on the structure
      analyzed and that mRNA editing activity may compensate possible genetically
      controlled functional effects. The incomplete coverage of the HTR2C variants is
      proposed as the best cost-benefit ratio bias to fix. The evidence of brain area
      specific HTR2C mRNA editing opens a debate about how the brain can differently
      modulate stress events, and process antidepressant treatments, in different brain
      areas. The mRNA editing activity on HTR2C may play a major role for the negative
      association results.

PMID- 18802919
TI  - A common haplotype at the dopamine transporter gene 5' region is associated with
      attention-deficit/hyperactivity disorder.
AB  - The dopamine transporter (DAT) is the major site of methylphenidate action, which
      is one of the main drugs used to treat attention-deficit/hyperactivity disorder
      (ADHD). Most association studies with ADHD focused in a VNTR at the 3'
      untranslated region of the gene (3'UTR) presenting conflicting results. However,
      the most common explanation to inconsistent results is variable linkage
      disequilibrium with an adjacent functional variant, just a few number of DAT1
      studies have reported LD structure across the gene. In this study, we screened 16
      polymorphisms across the DAT1 gene to understand LD structure in a Brazilian
      sample of families with ADHD probands and to verify if there were evidence for a
      biased transmission of alleles and haplotypes from parents to their 243 children
      with ADHD. In the DSM-IV combined subtype, we observed a preferential
      transmission of the haplotype A/C/C/C/A derived from five SNPs (rs2550948,
      rs11564750, rs261759, rs2652511, rs2975223) in 5' region (P corrected = 0.018)
      and no association with any allele/haplotype at the 3' region of the gene,
      including the 3' VNTR and the VNTR of intron 8. These results suggest a role for
      the promoter region in ADHD susceptibility and that allele heterogeneity should
      be highly considered in DAT1 gene association studies highlighting the importance
      of this gene in the genetics of the disorder.

PMID- 18802920
TI  - Secretion of active membrane type 1 matrix metalloproteinase (MMP-14) into
      extracellular space in microvesicular exosomes.
AB  - Membrane type 1 matrix metalloproteinase (MT1-MMP, MMP14) is an efficient
      extracellular matrix (ECM) degrading enzyme that plays important roles in tissue
      homeostasis and cell invasion. Like a number of type I membrane proteins, MT1-MMP
      can be internalized from the cell surface through early and recycling endosomes
      to late endosomes, and recycled to the plasma membrane. Late endosomes
      participate in the biogenesis of small (30-100 nm) vesicles, exosomes, which
      redirect plasma membrane proteins for extracellular secretion. We hypothesized
      that some of the endosomal MT1-MMP could be directed to exosomes for
      extracellular release. Using cultured human fibrosarcoma (HT-1080) and melanoma
      (G361) cells we provide evidence that both the full-length 60 kDa and the
      proteolytically processed 43 kDa forms of MT1-MMP are secreted in exosomes. The
      isolated exosomes were identified by their vesicular structure in electron
      microscopy and by exosomal marker proteins CD9 and tumor susceptibility gene
      (TSG101). Furthermore, exosomes contained beta1-integrin (CD29). The exosomes
      were able to activate pro-MMP-2 and degrade type 1 collagen and gelatin,
      suggesting that the exosomal MT1-MMP was functionally active. The targeting of
      MT1-MMP in exosomes represents a novel mechanism for cancer cells to secrete
      membrane type metalloproteolytic activity into the extracellular space.

PMID- 18802921
TI  - Human head and neck squamous cell carcinoma cells are both targets and effectors
      for the angiogenic cytokine, VEGF.
AB  - Former vascular endothelial growth factor (VEGF)-head and neck squamous cell
      carcinoma (HNSCC) studies have focused on VEGF's contributions toward tumor
      associated angiogenesis. Previously, we have shown that HNSCC cells produce high
      levels of VEGF. We therefore hypothesized that VEGF serves a biphasic role, that
      is, pro-angiogenic and pro-tumorigenic in HNSCC pathogenesis. Western blots
      confirmed the presence of VEGF's primary mitogenic receptors, VEGFR-2/KDR and
      VEGFR-1/Flt-1 in cultured HNSCC cells. Subsequent studies evaluated VEGF's
      effects on HNSCC intracellular signaling, mitogenesis, invasive capacities, and
      matrix metalloproteinases (MMPs) activities. Introduction of hrVEGF(165)
      initiated ROS-mediated intracellular signaling, resulting in kinase activation
      and phosphorylation of KDR and Erk1/2. As high endogenous VEGF production
      rendered HNSCC cells refractory to exogenous VEGF's mitogenic effects, siRNA was
      employed, inhibiting endogenous VEGF production for up to 96 h. Relative to
      transfection vector matched controls, siRNA treated HNSCC cells showed a
      significant decrease in proliferation at both 30 and 50 nM siRNA doses. Addition
      of exogenous hrVEGF(165) (30 and 50 ng/ml) to siRNA-silenced HNSCC cells resulted
      in dose-dependent increases in cell proliferation. Cell invasion assays showed
      VEGF is a potent HNSCC chemoattractant and demonstrated that VEGF pre-treatment
      enhanced invasiveness of HNSCC cells. Conditioned media from VEGF challenged
      HNSCC cells showed a moderate increase in gelatinase activity. Our results
      demonstrate, for the first time, that HNSCC cells are both targets and effectors
      for VEGF. These data introduce the prospect that VEGF targeted therapy has the
      potential to fulfill both anti-angiogenic and anti-tumorigenic functions.

PMID- 18802922
TI  - Specific signaling cascades involved in cell spreading during healing of micro
      wounded gastric epithelial monolayers.
AB  - Mechanisms that specifically modulate cell spreading and/or cell migration
      following epithelial wounding are poorly understood. Using micro-wounded human
      gastric epithelial monolayers, we show herein that EGF and TGFalpha maximally
      increase spreading of epithelial sheets under a cell proliferation-independent
      mechanism. Treatment of confluent HGE-17 cells with the phosphatidylinositol 3
      kinase inhibitor, LY294002, and the epidermal growth factor receptor inhibitor,
      PD153035, strongly reduced basal and TGFalpha-stimulated cell spreading. While
      pharmacological inhibition of pp60src-kinase activity also attenuated basal
      epithelial spreading, addition of the mTOR/p70S6K inhibitor rapamycin or a
      specific siRNA targeting ILK sequence did not affect the kinetic rates of wound
      closure. Epithelial wound healing was initiated by actin purse-string contraction
      followed by lamellae formation. Conversely, disruption of actin and tubulin
      stability with cytochalasin D and nocodazole, respectively, inhibited epithelial
      sheet spreading. Finally, antibodies directed against the alpha3 integrin
      subunit, but not against the alpha6 or alpha2 subunits, attenuated epithelial
      sheet spreading as well as lamellae formation. In conclusion, the current
      investigation establishes that EGF/TGFalpha and the alpha3beta1 integrin, pp60c
      src, EGFR and PI3K pathways are mainly associated with the cell spreading of the
      restitution process during healing of human gastric epithelial wounds.

PMID- 18802923
TI  - The impact of individual and methodological factors in the variability of
      response to methylphenidate in ADHD pharmacogenetic studies from four different
      continents.
AB  - Several studies have evaluated the association between individual polymorphisms
      and response to methylphenidate (MPH) in subjects with attention
      deficit/hyperactivity disorder (ADHD). There are few replication studies for each
      polymorphism of interest and results are sometimes inconsistent in this field.
      Although data collection from multiple international sites would allow large
      sample sizes, this approach has been criticized for introducing sampling
      variability due to differences in ethnicity and methodology between studies. To
      examine these issues, we aggregated nine pharmacogenetic studies from four
      different continents and conducted a two stage analysis: (a) we evaluated the
      role of methodological aspects in the variability of ADHD symptom improvement
      between studies using meta-regression analysis; (b) we assessed the role of
      individual characteristics of the subjects in the variability of ADHD symptoms
      improvement using multivariate regression analysis in the same data sets. At the
      study level, from five evaluated factors, only the design of the study (open
      studies vs. randomized controlled trials) was significantly associated with
      heterogeneity of results (P = 0.001). At the individual level, age (P < 0.001),
      comorbid oppositional defiant disorder (P < 0.001), and pre-treatment scores (P <
      0.001) were associated with change of ADHD scores with treatment in the final
      multivariate model. Our results suggest that joint analyses of pharmacogenetic
      studies are feasible and promising, since fixed variables, such as the site where
      the study was conducted, were not related to results. Nevertheless, stratified
      analyses according to the design of the study must be preferentially conducted
      and the role of individual factors such as demographic data and comorbid profile
      as confounders should be assessed.

PMID- 18802924
TI  - Association of the dopamine transporter (SLC6A3/DAT1) gene 9-6 haplotype with
      adult ADHD.
AB  - ADHD is a neuropsychiatric disorder characterized by chronic hyperactivity,
      inattention and impulsivity, which affects about 5% of school-age children. ADHD
      persists into adulthood in at least 15% of cases. It is highly heritable and
      familial influences seem strongest for ADHD persisting into adulthood. However,
      most of the genetic research in ADHD has been carried out in children with the
      disorder. The gene that has received most attention in ADHD genetics is
      SLC6A3/DAT1 encoding the dopamine transporter. In the current study we attempted
      to replicate in adults with ADHD the reported association of a 10-6 SLC6A3
      haplotype, formed by the 10-repeat allele of the variable number of tandem repeat
      (VNTR) polymorphism in the 3' untranslated region of the gene and the 6-repeat
      allele of the VNTR in intron 8 of the gene, with childhood ADHD. In addition, we
      wished to explore the role of a recently described VNTR in intron 3 of the gene.
      Two hundred sixteen patients and 528 controls were included in the study. We
      found a 9-6 SLC6A3-haplotype, rather than the 10-6 haplotype, to be associated
      with ADHD in adults. The intron 3 VNTR showed no association with adult ADHD. Our
      findings converge with earlier reports and suggest that age is an important
      factor to be taken into account when assessing the association of SLC6A3 with
      ADHD. If confirmed in other studies, the differential association of the gene
      with ADHD in children and in adults might imply that SLC6A3 plays a role in
      modulating the ADHD phenotype, rather than causing it.

PMID- 18802925
TI  - Lysophosphatidic acid activates telomerase in ovarian cancer cells through
      hypoxia-inducible factor-1alpha and the PI3K pathway.
AB  - Telomerase is reactivated in over 90% of tumors and plays critical roles in tumor
      progression. The mechanisms by which telomerase is up-regulated in cancer cells
      are poorly understood. Here we showed that a bioactive lipid, lysophophatidic
      acid (LPA), up-regulated the expression of human telomerase reverse transcriptase
      (hTERT) and telomerase activity in serous ovarian adenocarcinoma cell lines
      SKOV3, A2780, and HEY, but not in OCC1, a clear cell ovarian cancer cell line.
      This cell type specific effect of LPA on telomerase regulation may reflect
      distinctive genetic backgrounds in different histological subtype of ovarian
      cancer cells. Our data further suggest that the phosphatidylinositol 3-phosphate
      kinase (PI3K) pathway and hypoxia-inducible factor-1alpha (HIF-1alpha) are likely
      to be involved in LPA-induced hTERT expression. Targeting human telomerase by LPA
      is potentially involved in its role of promoting tumor progression.

PMID- 18802927
TI  - Inhibition of hyaluronan export attenuates cell migration and metastasis of human
      melanoma.
AB  - When secreted from malignant cells, hyaluronan facilitates tumor invasion and
      metastasis, as inhibition of its export by zaprinast inhibited metastasis
      formation in mice. However, the precise steps of the metastatic cascade, which
      were influenced by zaprinast, have not been identified as yet. Here we analyzed
      the cell biological effects of the inhibitor on three human melanoma cell lines
      that differed in their hyaluronan production and their metastatic capability when
      xenografted into SCID mice. We measured the influence of zaprinast on cellular
      hyaluronan export, surface coat formation, proliferation, random migration,
      colony formation in soft agar, adhesion, and transepithelial resistance.
      Concentrations of zaprinast not affecting cell proliferation, adhesion and
      transepithelial resistance, nevertheless reduced hyaluronan export by 50%,
      surface coat formation, random migration, and colony formation in soft agar.
      These results indicate that hyaluronan enhances metastasis formation primarily in
      those steps of the metastatic cascade, which involves tumor cell migration.

PMID- 18802926
TI  - Prevalence of and risk factors for prostatitis in African American men: the Flint
      Men's Health Study.
AB  - INTRODUCTION: Prostatitis is a common, yet ill-defined condition without clear
      diagnostic criteria and treatment strategies. Previous studies examining the
      prevalence and correlates of prostatitis are limited in their inclusion of
      primarily white populations. The objective of the current study was to identify
      prevalence of and risk factors for prostatitis in a population-based sample of
      African-American men. METHODS: In 1996, a probability sample of 703 African
      American men, aged 40-79, residing in Genesee County, Michigan without a prior
      history of prostate cancer/surgery provided responses to a structured interview
      administered questionnaire which elicited information regarding
      sociodemographics, current stress and health ratings, and past medical history,
      including history of physician diagnosed prostatitis, BPH and sexually
      transmitted diseases. Logistic regression was used to identify predictors of
      prostatitis after adjustment for age. RESULTS: Forty-seven (6.7%) of the 703 men
      reported a history of prostatitis. Increased frequency of sexual activity and
      physical activity were significantly associated with decreased odds of disease.
      Moderate to severe lower urinary tract symptoms (LUTS) and a history of BPH were
      significantly associated with prostatitis after adjustment for age. CONCLUSION:
      After adjustment for age, LUTS severity and history of BPH were associated with
      increased odds of prostatitis. BMI, physical activity and sexual frequency were
      associated with decreased odds of prostatitis. Finally, poor emotional and
      physical health, high perceived stress and low social support were associated
      with an increased risk of prostatitis history. Importantly, these findings
      suggest that the primary risk factors for this condition are largely modifiable
      and highlight potential targets for future prevention.

PMID- 18802928
TI  - Association between catechol O-methyltransferase (COMT) haplotypes and severity
      of hyperactivity symptoms in adults.
AB  - It has been suggested that symptoms of attention-deficit/hyperactivity disorder
      (ADHD) is related to low dopamine levels in the prefrontal cortex. The enzyme
      catechol O-methyltransferase (COMT), which degrades dopamine and other
      catecholamines, is important for monoamine signaling in this brain-region, but
      genetic studies of the functional Val158Met (rs4680) polymorphism in ADHD have
      been inconsistent. However, recently it was shown that also common synonymous
      COMT variants modulate total COMT enzymatic activity by affecting the expression
      of the gene [Nackley et al. (2006); Science 314(5807):1930-1933]. We therefore
      hypothesized that analysis of haplotypes could reveal more about the association
      between COMT and ADHD symptoms than the Val158Met polymorphism alone. SNPs
      rs6269, rs4633, rs4818, and rs4680, tagging the common putative functional COMT
      haplotypes, were genotyped in 435 adult subjects with a clinical diagnosis of
      ADHD and 383 controls and analyzed for association with ADHD and the
      hyperactivity/impulsivity and inattention dimensions from the Adult ADHD Self
      Report Scale (ASRS). All markers showed a trend for association with the
      hyperactivity/impulsivity scale, peaking at marker rs6269 (P = 0.007). Haplotype
      analysis revealed that the rs6269 risk allele tags the suggested high COMT
      activity haplotype, which is associated with the highest
      hyperactivity/impulsivity score in our sample (P = 0.01). Our results also
      suggest that there is a stepwise decreased hyperactivity/impulsivity score
      associated with the proposed mid and low activity haplotypes described
      previously. In conclusion, we suggest that COMT haplotype variation is associated
      primarily with the hyperactivity/impulsivity dimension of ADHD and point to the
      importance of testing this hypothesis in future studies.

PMID- 18802929
TI  - MYC translocation-negative classical Burkitt lymphoma cases: an alternative
      pathogenetic mechanism involving miRNA deregulation.
AB  - The molecular feature of Burkitt lymphoma (BL) is the translocation that places c
      Myc under the control of immunoglobulin gene regulatory elements. However, there
      is accumulating evidence that some cases may lack an identifiable MYC
      translocation. In addition, during the EUROFISH project, aiming at the
      standardization of FISH procedures in lymphoma diagnosis, we found that five
      cases out of 35 classic endemic BLs were negative for MYC translocations by using
      a split-signal as well as a dual-fusion probe. Here we investigated the
      expression pattern of miRNAs predicted to target c-Myc, in BL cases, to clarify
      whether alternative pathogenetic mechanisms may be responsible for
      lymphomagenesis in cases lacking the MYC translocation. miRNAs are a class of
      small RNAs that are able to regulate gene expression at the post-transcriptional
      level. Several studies have reported their involvement in cancer and their
      association with fragile sites in the genome. They have also been shown to
      control cell growth, differentiation, and apoptosis, suggesting that these
      molecules could act as tumour suppressors or oncogenes. Our results demonstrated
      a modulation of specific miRNAs. In particular, down-regulation of hsa-let-7c was
      observed in BL cases, compared to normal controls. More interestingly, hsa-mir
      34b was found to be down-regulated only in BL cases that were negative for MYC
      translocation, suggesting that this event might be responsible for c-Myc
      deregulation in such cases. This hypothesis was further confirmed by our in vitro
      experiments, which demonstrated that increasing doses of synthetic hsa-mir-34b
      were able to modulate c-Myc expression. These results indicate for the first time
      that hsa-mir-34b may influence c-Myc expression in Burkitt lymphoma as the more
      common aberrant control exercised by the immunoglobulin enhancer locus.

PMID- 18802930
TI  - Probing the limits of molecular imprinting: strategies with a template of limited
      size and functionality.
AB  - A series of polymers molecularly imprinted with the general anaesthetic propofol
      were synthesized using both semi- and non-covalent approaches. The polymers were
      evaluated with respect to template rebinding in both aqueous and organic media.
      In aqueous media, the observed propofol binding in these polymer systems was
      largely hydrophobic and non-specific in nature. In non-polar solvents such as
      hexane, electrostatic (hydrogen bonding) interactions dominate resulting in some
      selectivity. The implication of these results, in conjunction with those obtained
      using structures of similar size in other studies, is that propofol, a template
      possessing limited functionality and size, appears to define the lower limit for
      template size and degree of functionalization that can be used for the creation
      of ligand-selective recognition sites in molecularly imprinted polymers.
      Furthermore, studies with alternative ligands indicate that the steric crowding
      of a ligand's functionality to the polymer contributes to the extent of polymer
      ligand recognition.

PMID- 18802931
TI  - Intrinsic disorder explains diverse nuclear roles of chromatin remodeling
      proteins.
AB  - Chromatin remodelers, a group of proteins involved in nucleosome re-positioning
      and modification, have extensive range of interacting partners. They form
      multimeric complexes and interact with modified histones, transcription,
      splicing, and replication factors, DNA, RNA, and the factors related to the
      maintenance of chromosome structure. Such diverse range of interactions is hard
      to explain with the presumed highly structured form of the protein. In the
      current analysis, the conformations of chromatin remodelers were explored using
      protein disorder prediction algorithms. The study revealed that a significant
      proportion (p < 2.2e-16) of these proteins harbor at least one long region of
      intrinsic disorder (>70 aa). These unstructured regions do not exhibit any
      preference to the N/C terminal or middle of the protein. They do not show any
      significant representation in the Protein Data Bank (PDB) structure repository.
      Limited examples from PDB indicate direct involvement of disordered regions in
      binding of chromatin remodeling proteins to naked or modified DNA, histones, and
      other chromatin-related factors. Furthermore, intrinsic disorder seen in these
      proteins correlates to the presence of low sequence complexity regions (p =
      1.851e-10) particularly the tandem repeats of hydrophilic and charged amino
      acids. This probably hints at their evolutionary origin via repeat expansion. The
      disordered regions may enable these proteins to reversibly bind to various
      interacting partners and eventually contribute to functional diversity and
      specialization of chromatin remodeling complexes. These could also endow
      combinatorial action of multiple domains within a protein. We further discuss the
      prominent association of intrinsic disorder with other chromatin-related proteins
      and its functional relevance therein.

PMID- 18802932
TI  - Variability of body weight, pulse pressure and glycaemia strongly predict total
      mortality in elderly type 2 diabetic patients. The Verona Diabetes Study.
AB  - BACKGROUND: Ageing is characterized by a decreased functional reserve, a concept
      defined as homeostenosis. We assessed the impact of long-term exposure to the
      average value (mean) or to the variability (coefficient of variation) of fasting
      glycaemia, body mass index (BMI) and pulse pressure on total mortality in a
      cohort of type 2 diabetic patients. METHODS: Fasting glycaemia, BMI and pulse
      pressure values were collected over a period of 3 years in 1 319 type 2 diabetic
      patients who were subsequently followed up for 10 years. For each patient, the
      means and the coefficients of variation of fasting glycaemia, BMI and pulse
      pressure were computed. The adverse impact of these risk factors on total
      mortality was assessed in patients aged < 65 years (n = 565) and in those aged >
      or = 65 years (n = 754), separately. RESULTS: During the 10 years of follow-up,
      438 patients died. In younger diabetic patients, the means of fasting glycaemia
      [hazard ratio (HR) of III tertile versus I tertile = 2.11, 95% confidence
      interval (CI): 1.22-3.64], BMI (HR = 1.88, 1.12-3.14) and pulse pressure (HR =
      2.36, 1.34-4.16) were independently associated with total mortality, while in
      older patients they were not. In contrast, the coefficients of variation of
      glycaemia (HR = 1.56, 1.17-2.08), BMI (HR = 1.34, 1.03-1.75) and pulse pressure
      (HR = 1.34, 1.03-1.74) independently predicted total mortality only in older
      patients. CONCLUSIONS: Our findings suggest that the variability of fasting
      glycaemia, body weight and blood pressure (BP) is independently associated with
      an increased risk of all-cause mortality in older type 2 diabetic patients.
      Future studies are required to confirm the reproducibility of our findings.

PMID- 18802933
TI  - Cellular cholesterol efflux to serum is impaired in diabetic nephropathy.
AB  - BACKGROUND: Cholesterol efflux from cells is an early step of reverse cholesterol
      transport (RCT) and the capacity of serum to induce cellular cholesterol efflux
      has recently been shown to be an independent predictor of coronary artery
      atherosclerosis. Our aim is to evaluate the capacity of serum to induce ATP
      binding cassette transporter A1 (ABCA1) and scavenger receptor class B type I (SR
      BI) mediated cholesterol efflux in type 2 diabetic patients with nephropathy.
      METHODS: Diabetic patients were recruited according to their urinary albumin
      excretion rate (normoalbuminuria, microalbuminuria and proteinuria) with 20
      subjects in each group and compared with 20 age-matched controls. The ability of
      the serum to induce cholesterol efflux was measured using a cell culture system.
      RESULTS: Serum capacity to induce ABCA1-mediated cholesterol efflux was decreased
      in patients with microalbuminuria or proteinuria (p < 0.05) whereas SR-BI
      mediated cholesterol efflux was impaired in all three groups of diabetic patients
      (p < 0.05). Plasma high-density lipoprotein (HDL) cholesterol and apoAI were
      reduced in all groups of diabetic patients, but pre-beta-HDL was only
      significantly decreased in those with microalbuminuria or proteinuria. Serum
      advanced glycation end products (AGEs) were significantly increased in diabetic
      patients with microalbuminuria or proteinuria. Serum AGEs and pre-beta-HDL were
      the significant independent determinants of ABCA1-mediated cholesterol efflux,
      whereas plasma HDL and log (creatinine) were the significant determinants of SR
      BI-mediated cholesterol efflux. CONCLUSION: The capacity of serum to induce ABCA1
      and SR-BI-mediated cholesterol efflux was impaired in diabetic patients with
      incipient or overt nephropathy. These abnormalities may contribute to the
      accelerated development of atherosclerotic vascular disease in these patients.

PMID- 18802934
TI  - Nanomedicine and its potential in diabetes research and practice.
AB  - Nanomedicine involves measurement and therapy at the level of 1-100 nm. Although
      the science is still in its infancy, it has major potential applications in
      diabetes. These include solving needs such as non-invasive glucose monitoring
      using implanted nanosensors, with key techniques being fluorescence resonance
      energy transfer (FRET) and fluorescence lifetime sensing, as well as new nano
      encapsulation technologies for sensors such as layer-by-layer (LBL) films. The
      latter might also achieve better insulin delivery in diabetes by both improved
      islet encapsulation and oral insulin formulations. An 'artificial nanopancreas'
      could be an alternative closed-loop insulin delivery system. Other applications
      of nanomedicine include targeted molecular imaging in vivo (e.g. tissue
      complications) using quantum dots (QDs) or gold nanoparticles, and single
      molecule detection for the study of molecular diversity in diabetes pathology.

PMID- 18802936
TI  - Cooperativity between the beta-tubulin carboxy tail and the body of the molecule
      is required for microtubule function.
AB  - Using Drosophila spermatogenesis as a model, we show that function of the beta
      tubulin C-terminal tail (CTT) is not independent of the body of the molecule. For
      optimal microtubule function, the beta-tubulin CTT and body must match. beta2 is
      the only beta-tubulin used in meiosis and spermatid differentiation. beta1
      tubulin is used in basal bodies, but beta1 cannot replace beta2. However, when
      beta1 is co-expressed with beta2, both beta-tubulins are equally incorporated
      into all microtubules, and males exhibit near wild type fertility. In contrast,
      co-expression of beta2beta1C and beta1beta2C, two reciprocal chimeric molecules
      with bodies and tails swapped, results in defects in meiosis, cytoskeletal
      microtubules, and axonemes; males produce few functional sperm and few or no
      progeny. In these experiments, all the same beta-tubulin parts are present, but
      unlike the co-assembled native beta-tubulins, the "trans" configuration of the co
      assembled chimeras is poorly functional. Our data thus reveal essential intra
      molecular interactions between the CTT and other parts of the beta-tubulin
      molecule, even though the CTT is a flexible surface feature of tubulin
      heterodimers and microtubules. In addition, we show that Drosophila sperm tail
      length depends on the total tubulin pool available for axoneme assembly and
      spermatid elongation. D. melanogaster and other Drosophila species have
      extraordinarily long sperm tails, the length of which is remarkably constant in
      wild type flies. We show that in males of experimental genotypes that express
      wild type tubulins but have half the amount of the normal tubulin pool size,
      sperm tails are substantially shorter than wild type.

PMID- 18802937
TI  - Cultural consonance, a 5HT2A receptor polymorphism, and depressive symptoms: a
      longitudinal study of gene x culture interaction in urban Brazil.
AB  - In this study in urban Brazil we examine, as a predictor of depressive symptoms,
      the interaction between a single nucleotide polymorphism in the 2A receptor in
      the serotonin system (-1438G/A) and cultural consonance in family life, a measure
      of the degree to which an individual perceives her family as corresponding to a
      widely shared cultural model of the prototypical family. A community sample of
      144 adults was followed over a 2-year-period. Cultural consonance in family life
      was assessed by linking individuals' perceptions of their own families with a
      shared cultural model of the family derived from cultural consensus analysis. The
      -1438G/A polymorphism in the 2A serotonin receptor was genotyped using a standard
      protocol for DNA extracted from leukocytes. Covariates included age, sex,
      socioeconomic status, and stressful life events. Cultural consonance in family
      life was prospectively associated with depressive symptoms. In addition, the
      interaction between genotype and cultural consonance in family life was
      significant. For individuals with the A/A variant of the -1438G/A polymorphism of
      the 2A receptor gene, the effect of cultural consonance in family life on
      depressive symptoms over a 2-year-period was larger (beta = -0.533, P < 0.01)
      than those effects for individuals with either the G/A (beta = -0.280, P < 0.10)
      or G/G (beta = -0.272, P < 0.05) variants. These results are consistent with a
      process in which genotype moderates the effects of culturally meaningful social
      experience on depressive symptoms.

PMID- 18802938
TI  - Outcome and toxicity of chemotherapy for acute lymphoblastic leukemia in children
      with Down syndrome.
AB  - BACKGROUND: Acute lymphoblastic leukemia (ALL) in children with Down syndrome
      (DS) presents with an increased incidence, higher frequency of adverse effects
      and inferior probability of survival. Attempts at improving outcomes face the
      dilemma posed by the need to avoid excessive toxicity while maintaining the
      efficacy of treatment. Dose reductions and avoidance of infusions of intermediate
      and high-dose methotrexate are common in this group. PROCEDURE: In a matched pair
      analysis we compared adverse effects and survival after ALL chemotherapy using
      intermediate and high doses of methotrexate in children with and without Down
      syndrome. RESULTS: Following intermediate and high doses of methotrexate to treat
      primary ALL, children with DS did not require opiate analgesia and parenteral
      nutrition for severe mucositis more often than children without DS. Children with
      DS spent more days in hospital and missed more doses of maintenance chemotherapy.
      Chemotherapy dose reductions were common and in this study had no detectable
      adverse impact. Event-free and overall survival (OS) of children with ALL was
      lower in the DS than the non-Down syndrome (NDS) control group. The difference,
      however, was no longer significant during the recent treatment era. CONCLUSIONS:
      The feasibility of all treatment elements that are efficacious in pediatric ALL
      needs to be carefully considered in children with DS. In addition to survival
      data, the prospective collection of data on both adverse events and treatment
      modifications is essential to strike a balance between the avoidance of adverse
      effects and the need for intensive therapy that will safely improve ALL outcomes
      in this group.

PMID- 18802939
TI  - Dynamic in-hand movements in adult and young juvenile chimpanzees (Pan
      troglodytes).
AB  - Descriptions of manual function in nonhuman primates have largely focused on
      static precision and power grasping (as first defined by Napier,1956), while
      identification and description of dynamic manual function are rare and
      incomplete. Here, we describe several forms of in-hand movements used by
      chimpanzees (Pan troglodytes) when manipulating small objects. In-hand movements
      are defined as the movement of an object within one hand via manipulation of the
      digits. We presented adult and young juvenile chimpanzees (ages 5-29 years) with
      a task that required inserting small objects through correspondingly shaped
      cutouts in a transparent Plexiglas panel. While attempting to insert the objects
      through the cutouts, the subjects used at least two forms of in-hand movements to
      change their grip on the object for more precise alignment. We describe in detail
      the in-hand movements they used and the variability observed in form and
      execution among the subjects. In general, the adult subjects used in-hand
      movements more frequently and used a wider variety of forms than did the young
      juvenile subjects, suggesting that in-hand movements are in the process of fine
      tuning around the age of 5 years in chimpanzees. The dexterity exhibited by the
      adults, however, shows that the neuromuscular and morphological requirements for
      relatively complex digital manipulation are present in the adult chimpanzee.

PMID- 18802940
TI  - Primary pulmonary rhabdomyosarcoma in childhood: clinico-biologic features in two
      cases with review of the literature--erratum.

PMID- 18802941
TI  - Identification of a novel mutation in DKC1 in dyskeratosis congenita.
AB  - Dyskeratosis congenita (DC) is a rare congenital syndrome characterized by the
      triad of reticular skin pigmentation, nail dystrophy and mucosal leukoplakia, and
      the predisposition to bone marrow failure and malignancy. DC is genetically
      heterogeneous and X-linked and autosomal forms of the disease exist. Here, we
      report the clinical description and mutation analysis of a Russian family with X
      linked DC. A novel mutation in DKC1 raised de novo in the maternal grandmother's
      gamete was found; this mutation is a 2 bp inversion in exon 3:
      NM_001363:c.166_167invCT (Leu56Ser).

PMID- 18802942
TI  - Transdermal buprenorphine in children with cancer-related pain.
AB  - We present three cases of children (aged 3-5 years) in which cancer-related pain
      was adequately controlled by Transdermal Buprenorphine. The endpoints for
      evaluating analgesic efficacy consisted of the assessment of pain using a visual
      scale and the possibility of reducing other pain treatment. Improvement of pain
      level was demonstrated by the decrease in pain scores, by reduction of the
      overall amount of medications, especially opioids, and by improvement of
      uninterrupted sleep. Only limited data is available on the use of Transdermal
      Buprenorphine in children. In our experience, Transdermal Buprenorphine allowed
      good analgesia without significant side effects in these three children with
      cancer-related pain.

PMID- 18802943
TI  - Cardiorespiratory fitness predicts later body mass index, but not other
      cardiovascular risk factors from childhood to adolescence.
AB  - We analyzed the 5-year longitudinal relationship between cardiorespiratory
      fitness (CRF) and cardiovascular diseases (CVD) risk factors in children. A total
      of 153 students (66 boys and 87 girls) were evaluated in 1998 and 2003.
      Multilevel modeling was used to determine the effect of CRF across time (Model 1,
      adjusted for time and Model 2-Model 1 with further adjustment for gender and
      age). In both models, a significant main effect was found for body mass index
      (BMI) (P <or= 0.05). Data showed that in children, lower levels of CRF are
      associated with higher levels of BMI over a 5-year follow-up period.

PMID- 18802944
TI  - Behavioral and nutritional factors and geohelminth infection among two ethnic
      groups in the Terai region, Nepal.
AB  - Geohelminthiasis is a major health problem in many developing countries. This
      study was designed to evaluate the role of behaviors and the nutritional status
      of people with geohelminth infection in two indigenous ethnic groups in lowland
      Terai, Nepal. One hundred and fourteen individuals (55 Mushar and 59 Tharu) aged
      20-60 years participated, and a structured questionnaire was used to investigate
      socioeconomic status and behaviors. Nutritional status was assessed by
      anthropometric measurements. Ninety five stool samples of the participants were
      collected for parasitological analysis. The results showed that the prevalence of
      geohelminthiasis was 42.1%: 26.3% of the subjects were infected with roundworm,
      9.5% with hookworms, and 6.3% with whipworm. Multivariate logistic regression
      analysis revealed that "not using soap for hand-washing" (adjusted OR = 5.27; 95%
      CI: 1.41-19.78) and height (adjusted OR = 0.88, 95% CI: 0.79-0.99) were
      associated with the prevalence of roundworm. "Walking barefoot when outdoor" was
      associated with the prevalence of hookworm (chi-square test, P = 0.01). Ethnicity
      was not associated with the prevalence of either of the geohelminths. Because
      unhygienic behaviors and chronic malnutrition were closely associated with the
      people's recognition and subsistence pattern, elimination of geohelminth
      infection in Terai would be possible if deworming campaigns were implemented with
      in-depth health education and modern agricultural technology.

PMID- 18802945
TI  - Let's image gently: reducing excessive reliance on CT scans.

PMID- 18802946
TI  - The prognostic value of tumor markers in newly diagnosed patients with primary
      central nervous system germ cell tumors.
AB  - BACKGROUND: To determine the impact of diagnostic serum and/or cerebrospinal
      fluid (CSF) alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin (b-HCG)
      elevations on survival in newly diagnosed patients with central nervous system
      germ cell tumors (CNS GCT) treated with chemotherapy with the intent to avoid
      irradiation. PROCEDURE: Seventy-five patients with newly diagnosed CNS GCT
      enrolled in two sequential internationally conducted clinical trials with serum
      and CSF AFP and b-HCG levels available from initial diagnosis were
      retrospectively analyzed. Subjects received platinum based chemotherapy and were
      followed with serial imaging and tumor marker evaluations. RESULTS: The 5-year
      overall survival (OS) and event free survival (EFS) for patients with normal
      tumor markers compared with those with elevated markers at diagnosis was 78% (95%
      CI 51-91%) versus 60% (95% CI 46-72%) (P = 0.08) and 22% (95% CI 7-43%) versus
      28% (95% CI 16-40%) (P = 0.68). The hazard ratio of death for patients with
      elevated markers was 1.9 times as high as that for those with normal markers (95%
      CI 0.58-6.5) after adjusting for other baseline characteristics. There was no
      observed difference in survival among patients with histologically confirmed
      germinomas, irrespective of level of b-HCG. CONCLUSIONS: Patients with elevated
      tumor markers appear to have poorer OS independent of tumor histology, although
      these differences do not reach statistical significance (P < or = 0.05). No
      differences were observed in EFS between groups likely due to the poor response
      of chemotherapy only approach to patients with normal markers. b-HCG elevations
      in biopsy proven germinomas do not seem to alter a patient's prognosis.

PMID- 18802948
TI  - Frequency and clinical features of the JAK2 V617F mutation in pediatric patients
      with sporadic essential thrombocythemia.
AB  - BACKGROUND: Pediatric essential thrombocythemia (ET) is a rare and heterogenous
      disease entity. While several recent studies have focused on the role of the JAK2
      V617F mutation in pediatric ET, the frequency of pediatric ET cases with this
      mutation and the associated clinical features remain unclear. PROCEDURE: We
      examined six childhood cases who had been diagnosed with ET according to WHO
      criteria (onset age: 0.2-14 years) for the presence of the JAK2 V617F mutation,
      MPLW515L mutation and JAK2 exon 12 mutations. Two sensitive PCR-based methods
      were used for the JAK2 V617F genotyping. We also examined the expression of
      polycythemia rubra vera-1 (PRV-1), which is a diagnostic marker for clonal ET.
      RESULTS: We found that three of the six cases had the JAK2 V617F mutation and
      that all six cases expressed PRV-1 in their peripheral granulocytes. Neither MPL
      W515L mutation nor JAK2 exon 12 mutations was detected in the patients without
      JAK2 V617F mutation. The two patients who developed thrombocythemia during
      infancy were JAK2 V617F-negative. CONCLUSIONS: These findings suggest that the
      JAK2 V617F mutation is not rare in childhood sporadic ET cases, and that these
      cases might be older and myeloproliferative features.

PMID- 18802947
TI  - Myeloablative chemotherapy with autologous bone marrow rescue in children and
      adolescents with recurrent malignant astrocytoma: outcome compared with
      conventional chemotherapy: a report from the Children's Oncology Group.
AB  - PURPOSE: Children and adolescents with malignant astrocytomas recurring after
      initial treatment have a dismal prognosis, with only rare patients surviving 1
      year beyond recurrence. The purpose of this study was to attempt to improve their
      survival. METHODS: Twenty-seven children and adolescents with malignant
      astrocytomas [17 glioblastoma multiforme and 10 anaplastic astrocytoma (AA)]
      following initial tumor progression, received myeloablative chemotherapy followed
      by autologous marrow rescue with one of three thiotepa and etoposide-based
      chemotherapy regimens, administered alone (n = 11) or combined with carmustine (n
      = 5) or carboplatin (n = 11). Time to progression and death following
      myeloablative chemotherapy for these patients was compared non-randomly with
      outcome of a contemporaneously treated cohort of similar patients who received
      only conventional chemotherapy following initial tumor progression. The two
      cohorts were compared for age, histology, prior therapies, extent of surgical
      resection at progression, and time from initial diagnosis to progression.
      RESULTS: Five of 27 children (two with glioblastoma multiforme and three with AA)
      survive event-free from 8.3 to 13.3 years (median of 11.1 years) following
      myeloablative chemotherapy. Of 56 children with recurrent malignant astrocytoma
      who received conventional chemotherapy following initial progression, no patient
      survives. Differences in distributions of survival were not significant when
      stratified by surgical debulking (P = 0.39). However, for patients who were
      surgically debulked, the survival distributions are significantly different (P =
      0.017). CONCLUSIONS: Myeloablative chemotherapy with autologous marrow rescue can
      produce durable remissions in children and young adults with recurrent malignant
      gliomas, in the setting of minimal residual tumor burden achieved surgically.

PMID- 18802949
TI  - Differential diagnosis and work-up of elevations of alkaline phosphatase
      following therapy for pediatric cancer.

PMID- 18802950
TI  - A solid-state NMR study of phase structure, molecular interactions, and mobility
      in blends of citric acid and paracetamol.
AB  - Citric acid anhydrate (CAA) and paracetamol (PARA), prepared as crystalline
      physical mixtures and as amorphous blends, were studied using (13)C solid-state
      cross polarization magic angle spinning (CPMAS) NMR. Amorphous blends showed
      significant line broadening from the conformational distribution as compared to
      the crystalline samples. Also, chemical shift variations were observed between
      crystalline and amorphous blends, which were attributed to differences in
      intermolecular interactions. Averaging of proton rotating-frame spin-lattice
      relaxation times (T(1rho)) probed via different (13)C sites in the amorphous
      blends confirmed molecular level mixing. For some, initially amorphous, sample
      compositions the onset of crystallization was evident directly from spectra and
      from the significantly longer T(1rho) relaxations. Thus, crystallization caused
      phase separation with properties of the two phases resembling those of pure CAA
      and PARA, respectively. (13)C spectra of amorphous 50/50 (w/w, %) CAA/PARA
      recorded from above the glass transition temperature broadened as the temperature
      increased to a maximum at T approximately T(g) + 33 K. This was the result of a
      dynamic interference between the line narrowing techniques being applied and the
      time scale of molecular reorientation in the miscible melt. The derived average
      correlation time was found to correspond well with previous results from melt
      rheology. We conclude that the underlying reasons for physical instability (i.e.,
      crystallization from the miscible melt, including molecular interactions and
      dynamics) of this class of amorphous binary mixtures can be effectively evaluated
      using NMR spectroscopy.

PMID- 18802951
TI  - Multicultural competence and evidence-based practice in group therapy.
AB  - The multicultural competence (MC) and evidence-based practice (EBP) initiatives
      have each generated healthy debates in the mental health field, with ample
      implications for clinical training and practice. Using two case illustrations, we
      highlight practical challenges and prospects in the intersection of MC and EBP.
      To facilitate complementary practice of MC and EBP, we offer strategies for the
      group therapist as a "local clinical scientist" to deliver culturally responsive
      treatments. We stress the importance of cultural adaptation of EBP models,
      namely, modifying evidence-based interventions that involve changes in service
      delivery, in the nature of the therapeutic relationship, or in components of the
      treatment itself to accommodate the cultural beliefs and behaviors of racial
      cultural minority clients. Cultural adaptation of EBP in group therapy needs to
      be grounded in developmental contextualism and social justice. We discuss the two
      cases with an eye toward advancing multicultural competence in group therapy.

PMID- 18802952
TI  - Clinical characteristics and outcome of children with Burkitt lymphoma in Uganda
      according to HIV infection.
AB  - BACKGROUND: Characteristics of children with Burkitt lymphoma (BL) and HIV
      infection have not been described in Uganda before. PROCEDURE: We reviewed
      records at Uganda Cancer Institute (UCI) for years 1994-2004, to compare clinical
      features and outcome of BL in children who are HIV positive and negative (HIV+,
      HIV-). As statistical methods we used Student's t-test, Chi-square and Kaplan
      Meier's to compare both groups. RESULTS: Of 1,462 records of children retrieved,
      228 met the eligibility criteria and were reviewed (158 HIV-, 70 HIV+). There
      were 139 (61%) males and 89 (39%) females. The mean age was 6.9 years (HIV+ 6.7,
      HIV- 7.1). One hundred seventy-one cases (75%) had facial tumor (HIV+ 71.4%, HIV-
      76.6%). HIV positive children presented significantly with extrafacial disease
      (lymphadenopathy 67%, hepatic masses 51%, and thoracic masses 10%). Presentation
      with advanced stage disease occurred more frequently in HIV positive patients
      compared to HIV negative patients. Treatment response rates to chemotherapy were
      similar irrespective of HIV status. However, overall survival was poorer in HIV
      positive patients with a median survival of 11.79 months (P-value < 0.000, 95% CI
      8.65-14.92). CONCLUSIONS: BL in Uganda presents frequently with facial disease
      irrespective of HIV status. However HIV+ BL also presents commonly with extra
      facial sites, mainly lymphadenopathy. There is no difference in response to
      treatment with chemotherapy, but HIV+ BL patients have poorer survival. There is
      need for further characterization of BL in Uganda to understand the role of HIV
      in disease process and outcome.

PMID- 18802953
TI  - Pitx2 deletion in pituitary gonadotropes is compatible with gonadal development,
      puberty, and fertility.
AB  - This report introduces a gonadotrope-specific cre transgenic mouse capable of
      ablating floxed genes in mature pituitary gonadotropes. Initial analysis of this
      transgenic line, Tg(Lhb-cre)1Sac, reveals that expression is limited to the
      pituitary cells that produce luteinizing hormone beta, beginning appropriately at
      e17.5. Cre activity is detectable by a reporter gene in nearly every LHbeta
      producing cell, but the remaining hormone-producing cell types and other organs
      exhibit little to no activity. We used the Tg(Lhb-cre)1Sac strain to assess the
      role Pitx2 in gonadotrope function. The gonadotrope-specific Pitx2 knockout mice
      exhibit normal expression of LHbeta, sexual maturation, and fertility, suggesting
      that Pitx2 is not required for gonadotrope maintenance or for regulated
      production of gonadotropins.

PMID- 18802954
TI  - Phenotypic analyses of a medaka mutant reveal the importance of bilaterally
      synchronized expression of isthmic fgf8 for bilaterally symmetric formation of
      the optic tectum.
AB  - Developing neural tubes are bilaterally symmetric in all vertebrate embryos,
      irrespective of the presence of gene networks that generate left-right asymmetry.
      To explore the mechanisms that underlie the bilaterally symmetric formation of
      the neural tube, we examined a medaka (Oryzias latipes) dominant mutant, Oot, the
      neural tube of which transiently lacks normal symmetry in the optic tectum. We
      found that spatial changes in isthmic fgf8 expression do not occur on one side of
      the mutant, resulting in a transient desynchronized expression that correlates
      with tectal asymmetry. The application of exogenous FGF8 on one side of a wild
      type embryo mimics the Oot phenotype, indicating that the bilaterally equivalent
      expression of isthmic fgf8 is crucial for the bilaterally symmetric development
      of the tectum. These results suggest that tectal symmetry is not a "default"
      state, but rather is maintained actively by a bilaterally coupled and
      synchronized regulation of isthmic fgf8 expression.

PMID- 18802955
TI  - Stepwise examination for differential diagnosis of primary lung cancer and breast
      cancer relapse presenting as a solitary pulmonary nodule in patients after
      mastectomy.
AB  - BACKGROUND AND OBJECTIVES: The distinction of primary lung from metastatic breast
      cancer is crucial in patients presenting with a solitary pulmonary nodule after
      mastectomy, because treatment strategies are completely different. Definitive
      diagnosis of these nodules, however, is often difficult. We assessed the
      feasibility of our diagnostic approach for these nodules and estimated the
      frequency of primary lung cancer occurrence in patients after mastectomy.
      METHODS: We evaluated solitary pulmonary nodules appearing in 48 patients after
      mastectomy. For histological examination, CT-guided needle aspiration biopsy (CT
      NAB) or trans-bronchial lung biopsy (TBLB) was performed. Besides conventional
      morphopathological examination, differential diagnosis was performed by
      immunohistochemical examination and evaluation using a molecular marker
      (mammaglobin 1). RESULTS: Biopsy specimens were obtained using minimally invasive
      methods, namely CT-NAB and TBLB, in 91.7% of patients. From 48 patients,
      differential diagnosis was obtained by morphopathological methods alone in 32,
      and by immunohistochemical and molecular marker examination in the remaining 16.
      Final diagnosis was metastatic breast and primary lung cancer in 40 (83.3%) and 8
      patients (16.7%), respectively. CONCLUSIONS: Our results show the clinical
      feasibility of our stepwise approach to the differential diagnosis of primary
      lung cancer and breast cancer relapse presenting as a solitary nodule in patients
      after mastectomy.

PMID- 18802956
TI  - Gastric cancer histology: clinicopathologic characteristics and prognostic value.
AB  - BACKGROUND AND OBJECTIVES: Gastric cancer can be divided into two major
      histologic categories, that is, differentiated and undifferentiated types. In the
      present study, we sought to clarify the prognoses and clinicopathologic
      characteristics of signet ring cell carcinoma and mucinous carcinoma, both of
      which are mucin-producing tumors of the undifferentiated type. METHODS: We
      retrospectively reviewed medical records of 2,275 patients who underwent gastric
      resection. Cases were divided into four histologic groups: differentiated
      carcinoma (well differentiated and moderately differentiated, WMD), poorly
      differentiated (PD), signet ring cell carcinoma (SRC), and mucinous carcinoma
      (MC). RESULTS: The overall cumulative 5-year survival rates for patients were 67%
      for WMD, 54% for PD, 65% for SRC, and 48% for MC. The outcome of SRC was similar
      to that of WMD, whereas that of MC was similar to that of PD. Stage-stratified
      analysis revealed that histologic type was not statistically related to survival
      in patients with stage I, II, or III. On the other hand, histologic type in
      patients with stage IV disease was found to be significantly associated with
      survival. CONCLUSIONS: Histologic classifications of mucin-producing gastric
      cancers should separately be considered from other histologic types.

PMID- 18802957
TI  - Breast cancer: from radical to minimal surgery.

PMID- 18802958
TI  - Gallbladder cancer (GBC): 10-year experience at Memorial Sloan-Kettering Cancer
      Centre (MSKCC).
AB  - BACKGROUND: The incidence of gallbladder cancer (GBC) in the US is 1.2/100,000.
      This report examines the patterns of presentation, adjuvant treatment and
      survival of a large cohort of patients with GBC evaluated at MSKCC over a 10-year
      period. METHODS: A retrospective analysis of patients referred to MSKCC with a
      diagnosis of GBC between January 1995 and December 2005 was performed. Patients
      were identified from the MSKCC cancer registry. Information extracted included,
      demographics, clinical and pathological stage, surgical management, pathology,
      adjuvant and palliative therapy, date of relapse, death or last follow-up. Date
      of diagnosis was defined as date of surgery or biopsy. Survival curves were
      estimated using the Kaplan-Meier method and compared using the log-rank test.
      RESULTS: Four hundred thirty-five GBC cases were identified: 285 (65.5%)
      females,150 (34.5%) males. Median age 67 years (range 28-100). Pathology: 88%
      adenocarcinoma, 4% squamous, 3% neuroendocrine, 2% sarcoma. 36.6% presented as
      AJCC Stage IV. 47% were discovered incidentally at laparoscopic cholecystectomy.
      One hundred thirty-six of these were re-explored, of whom 100 (73.5%) had
      residual disease. Of those who underwent curative resections (N = 123), 8 (6.5%)
      received adjuvant chemotherapy, 8 (6.5%) chemoradiation alone and 8 (6.5%) both
      chemoradiation and systemic chemotherapy. Median overall survival for the cohort
      was 10.3 months (95% CI 8.8-11.8) with a median follow up of 26.6 months. The
      median survival for those presenting with stage Ia-III disease was 12.9 months
      (95% CI 11.7-15.8 months) and 5.8 months (95% CI 4.5-6.7) for those presenting
      with stage IV disease. Median survival was 15.7 months (95% CI 12.4-18.4) for
      those discovered incidentally at laparoscopic cholecystectomy. For those who
      underwent re-exploration, median survival was 14.6 months (95% CI 12.6-18.3) if
      residual disease was present, and 72 months (95% CI 34 to infinity) if no
      evidence of disease. The median survival for those who received adjuvant therapy
      was 23.4 months (95% CI 15.7-47). CONCLUSIONS: GBC is commonly diagnosed
      incidentally (47%). Re-exploration reveals a high incidence of residual disease
      (74%). Median survival is better for patients who have no evidence of disease on
      re-exploration (72 months) compared to those with residual disease detected (P <
      0.0001). Overall prognosis is poor. Although we did not observe a survival
      benefit for those who received adjuvant therapy, the study did not have
      sufficient power to address this question. In addition, the number of patients
      who received adjuvant therapy was small with marked heterogeneity in clinical and
      therapeutic details, precluding any definitive conclusions being drawn.
      Prospective randomized trials of adjuvant therapy are needed in this disease.

PMID- 18802959
TI  - Novel caspase-suicide proteins for tamoxifen-inducible apoptosis.
AB  - Taking advantage of a mutant estrogen receptor ligand binding domain (ER(T2)), we
      developed novel Caspase fusion proteins for inducible apoptosis. We show that
      Caspase-ER(T2) fusion proteins become specifically activated by the synthetic
      ligand 4-OH- tamoxifen and rapidly induce apoptotic cell death in human, murine,
      and zebrafish cells. This novel tool for targeted cell ablation greatly
      facilitates the generation of disease models as well as developmental and
      regeneration studies in model organisms.

PMID- 18802960
TI  - Generation of Frizzled10-Cre transgenic mouse line: a useful tool for the study
      of dorsal telencephalic development.
AB  - Wnt signaling plays an important role in regulating cortical and hippocampal
      development, but many of the other molecular mechanisms underlying dorsal
      telencephalic development are largely unknown. We are taking advantage of the
      highly regionalized expression patterns of signaling components of the Wnt
      pathway to generate new mouse lines that will be useful for studying forebrain
      development. Here, we describe a transgenic mouse line where Cre is driven by the
      promoter of the Wnt receptor, Frizzled10. In these mice, Cre activity is mainly
      detected in the dorsal telencephalon during development and is confined to the
      pyramidal cell fields in the adult hippocampus. The Cre recombinase has very high
      efficiency when assayed by crossing the transgenic line with the ROSA26 reporter
      line. Thus, this Cre line will be useful for the study of dorsal telencephalic
      development and conditional inactivation of target genes in the cortex and
      hippocampus.

PMID- 18802961
TI  - Hepatitis C virus envelope components alter localization of hepatocyte tight
      junction-associated proteins and promote occludin retention in the endoplasmic
      reticulum.
AB  - Hepatocyte tight junctions (TJ) play key roles in characteristic liver functions,
      including bile formation and secretion. Infection by hepatitis C virus (HCV) may
      cause alterations of the liver architecture and disruption of the bile duct,
      which ultimately can lead to cholestasis. Herein, we employed the HCV replicon
      system to analyze the effect of HCV on TJ organization. TJ-associated proteins
      occludin, claudin-1, and Zonula Occludens protein-1 (ZO-1) disappeared from their
      normal localization at the border of adjacent cells in Huh7 clones harboring
      genomic but not subgenomic replicons expressing only the nonstructural proteins.
      Furthermore, cells containing genomic replicons showed a cytoplasmic accumulation
      of occludin in the endoplasmic reticulum (ER). TJ-associated function, measured
      as FITC-dextran paracellular permeability, of genomic replicon-containing cells,
      was also altered. Interestingly, clearance of the HCV replicon by interferon
      alpha (IFN-alpha) treatment and by short hairpin RNA (shRNA) significantly
      restored the localization of TJ-associated proteins. Transient expression of all
      HCV structural proteins, but not core protein alone, altered the localization of
      TJ-associated proteins in Huh7 cells and in clones with subgenomic replicons.
      Confocal analysis showed that accumulation of occludin in the ER partially co
      localized with HCV envelope glycoprotein E2. E2/occludin association was further
      confirmed by co-immunoprecipitation and pull-down assays. Additionally, using a
      cell culture model of HCV infection, we observed the cytoplasmic dot-like
      accumulation of occludin in infected Huh7 cells. CONCLUSION: We propose that HCV
      structural proteins, most likely those of the viral envelope, promote alterations
      of TJ-associated proteins, which may provide new insights for HCV-related
      pathogenesis.

PMID- 18802962
TI  - RNA-binding protein insulin-like growth factor II mRNA-binding protein 3
      expression promotes tumor invasion and predicts early recurrence and poor
      prognosis in hepatocellular carcinoma.
AB  - Insulin-like growth factor II mRNA-binding protein 3 (IMP3) is an RNA-binding
      protein expressed in embryonic tissues and multiple cancers. To investigate the
      role of IMP3 in hepatocellular carcinoma (HCC), its protein expression in the
      surgically resected unifocal tumors of 377 HCC patients (296 men and 81 women)
      with ages ranging from 7 to 88 years (mean, 55.49 years) was analyzed by
      immunohistochemistry. IMP3 was expressed in 255 (67.6%) of 377 resected unifocal
      primary HCCs. IMP3 protein was predominantly expressed in tumor border and
      invasive front, and it was more abundant in the satellite nodules and tumor
      thrombi than in the main tumors. The expression correlated with high alpha
      fetoprotein (>200 ng/mL, P < 1 x 10(-7)), larger tumor size (>5 cm, P = 0.006),
      high tumor grade (P < 1 x 10(-7)), and high tumor stage with vascular invasion
      and various degrees of intrahepatic metastasis (P < 1 x 10(-7)). IMP3 expression
      predicted early tumor recurrence (P < 1 x 10(-7)) and was a strong indicator of
      poor prognosis (P < 0.0001). Depletion of IMP3 with RNA interference in HCC cell
      line HA22T caused a decrease in cell motility, invasion, and transendothelial
      migration. Microarray analysis revealed that IMP3 depletion was associated with
      downregulation of multiple genes involved in tumor invasion. CONCLUSION: Our
      results indicate that IMP3 plays an important role in tumor invasion and
      metastasis and is a strong prognostic factor for patients with HCC.

PMID- 18802963
TI  - Evolutionary conservation of vertebrate notochord genes in the ascidian Ciona
      intestinalis.
AB  - To reconstruct a minimum complement of notochord genes evolutionarily conserved
      across chordates, we scanned the Ciona intestinalis genome using the sequences of
      182 genes reported to be expressed in the notochord of different vertebrates and
      identified 139 candidate notochord genes. For 66 of these Ciona genes expression
      data were already available, hence we analyzed the expression of the remaining 73
      genes and found notochord expression for 20. The predicted products of the newly
      identified notochord genes range from the transcription factors Ci-XBPa and Ci
      miER1 to extracellular matrix proteins. We examined the expression of the newly
      identified notochord genes in embryos ectopically expressing Ciona Brachyury (Ci
      Bra) and in embryos expressing a repressor form of this transcription factor in
      the notochord, and we found that while a subset of the genes examined are clearly
      responsive to Ci-Bra, other genes are not affected by alterations in its levels.
      We provide a first description of notochord genes that are not evidently
      influenced by the ectopic expression of Ci-Bra and we propose alternative
      regulatory mechanisms that might control their transcription.

PMID- 18802964
TI  - Calcium influx mechanisms underlying calcium oscillations in rat hepatocytes.
AB  - The process of capacitative or store-operated Ca(2+) entry has been extensively
      investigated, and recently two major molecular players in this process have been
      described. Stromal interacting molecule (STIM) 1 acts as a sensor for the level
      of Ca(2+) stored in the endoplasmic reticulum, and Orai proteins constitute pore
      forming subunits of the store-operated channels. Store-operated Ca(2+) entry is
      readily demonstrated with protocols that provide extensive Ca(2+) store
      depletion; however, the role of store-operated entry with modest and more
      physiological cell stimuli is less certain. Recent studies have addressed this
      question in cell lines; however, the role of store-operated entry during
      physiological activation of primary cells has not been extensively investigated,
      and there is little or no information on the roles of STIM and Orai proteins in
      primary cells. Also, the nature of the Ca(2+) influx mechanism with hormone
      activation of hepatocytes is controversial. Hepatocytes respond to physiological
      levels of glycogenolytic hormones with well-characterized intracellular Ca(2+)
      oscillations. In the current study, we have used both pharmacological tools and
      RNA interference (RNAi)-based techniques to investigate the role of store
      operated channels in the maintenance of hormone-induced Ca(2+) oscillations in
      rat hepatocytes. Pharmacological inhibitors of store-operated channels blocked
      thapsigargin-induced Ca(2+) entry but only partially reduced the frequency of
      Ca(2+) oscillations. Similarly, RNAi knockdown of STIM1 or Orai1 substantially
      reduced thapsigargin-induced calcium entry, and more modestly diminished the
      frequency of vasopressin-induced oscillations. CONCLUSION: Our findings establish
      that store-operated Ca(2+) entry plays a role in the maintenance of agonist
      induced oscillations in primary rat hepatocytes but indicate that other agonist
      induced entry mechanisms must be involved to a significant extent.

PMID- 18802965
TI  - Generation of a conditional null allele for Cftr in mice.
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR) gene encodes a
      cAMP-regulated chloride channel that is important in controlling the exchange of
      fluid and electrolytes across epithelial cells. Mutation of CFTR can lead to
      cystic fibrosis (CF), the most common lethal genetic disease in Caucasians. CF is
      a systemic illness with multiple organ systems affected including pulmonary,
      gastrointestinal, pancreatic, immune, endocrine, and reproductive systems. To
      understand the role of CFTR in the various tissues in which it is expressed, we
      generated a murine conditional null allele of Cftr (Cftr(fl10)) in which loxP
      sites were inserted around exon 10 of the Cftr gene. The Cftr(fl10) allele was
      validated by generating constitutive Cftr null (Cftr(Delta10)) mice using the
      protamine-cre system. The Cftr(Delta10/Delta10) mice displayed almost identical
      phenotypes to previously published CF mouse models, including poor growth,
      decreased survival, intestinal obstruction, and loss of Cftr function as assessed
      by electrophysiology measurements on gut and nasal epithelium. Mice containing
      the conditional null Cftr allele will be useful in future studies to understand
      the role of Cftr in specific tissues and developmental time points and lead to a
      better understanding of CF disease.

PMID- 18802966
TI  - Generation and characterization of EphA1 receptor tyrosine kinase reporter
      knockout mice.
AB  - Eph receptor tyrosine kinases (RTKs) are a highly conserved family of signaling
      proteins with functions in cellular migration, adhesion, apoptosis, and
      proliferation during both adult and embryonic life. Here, we describe a knock-in
      mouse in which EphA1 expression is disrupted via the insertion of an internal
      ribosome entry site (IRES)-human placental alkaline phosphatase (ALPP) reporter
      cassette into exon II of the EphA1 gene. This was shown to successfully knockout
      expression of endogenous EphA1 and enforce expression of the ALPP reporter by the
      EphA1 promoter. Staining for the ALPP reporter protein demonstrated an
      epithelially restricted expression pattern in mouse tissues. In EphA1 null mice,
      two separate phenotypes were identified: abnormal tail development manifesting as
      a kinky tail was found in approximately 80% of homozygous adults. A second,
      distinct abnormality present in approximately 18% of females was characterized by
      imperforate uterovaginal development with hydrometrocolpos and caused by a
      resistance of cells to apoptosis during reproductive tract canalization. These
      results indicate a possible role for EphA1 in tissue patterning and hormone
      induced apoptotic processes.

PMID- 18802967
TI  - Water-proton relaxivities of DNA oligomers carrying TEMPO radicals.
AB  - 5-Uridine derivative carrying a TEMPO radical (UST) was prepared and its single
      strand (ssUST) and a double strand (dsUST) with its complementary strand were
      obtained. Similarly, single strands carrying two and five radicals (ssUST2 and
      ssUST5, respectively) and the corresponding double strands (dsUST2 and dsUST5)
      were prepared. Their electron paramagnetic resonance (EPR) spectra showed typical
      anisotropic broadening in the high field line. The rotational correlation times,
      tau(R), estimated by analyzing the EPR spectra are 1.1 x 10(-10), 5.9 x 10(-10),
      and 14 x 10(-10) s for UST, ssUSTm, and dsUSTm, respectively. The water-proton
      relaxivities, r(1) and r(2), at 25 MHz, 0.59 T, and 25 degrees C, also increased
      in the same order and the r(1) values were 0.26, 0.41, and 0.56 mM(-1) s(-1) for
      UST, ssUSTm, and dsUSTm, respectively. The r(1) values of 1.00 and 2.06 mM(-1) s(
      1) for dsUST2 and dsUST5, respectively, were obtained.

PMID- 18802968
TI  - DFT calculations as a powerful technique to probe the crystal structure of
      Al(acac)3.
AB  - (27)Al, (17)O and (13)C chemical shieldings of aluminum acetylacetonate complex,
      Al(acac)(3), were calculated at some Density Functional Theory (DFT) levels of
      theory. In these calculations the X-ray structures of its different polymorphs
      were used. Using these calculated data observed discrepancies between the X-ray
      crystallography and solid state NMR experiment were explained in terms of the
      quality of the NMR data. In this survey we resorted to the simulated spectra
      using our calculated chemical shifts. In order to confirm our conclusions,
      electric field gradient (EFG) tensors of the (27)Al and (17)O nuclei were
      calculated at the same levels of theory as used in the chemical shielding
      calculations. On the other hand, these calculated chemical shifts and nuclear
      quadrupole coupling constants (NQCCs) made a correlation between X-ray
      crystallography and solid state NMR experiments.

PMID- 18802969
TI  - NMR analysis of a series of substituted pyrazolo[3,4-d] pyrimidines-4-amines.
AB  - A series of 21 substituted pyrazolo[3,4-d]pyrimidines-4-amines were studied by
      (1)H and (13)C NMR. The application of two-dimensional techniques, HMQC and HMBC,
      allowed the complete assignment of the spectra for all the compounds.

PMID- 18802970
TI  - Characterisation of uniformly 13C, 15N labelled bacteriochlorophyll a and
      bacteriopheophytin a in solution and in solid state: complete assignment of the
      13C, 1H and 15N chemical shifts.
AB  - In this investigation we report a complete assignment of (13)C, (1)H and (15)N
      solution and solid state chemical shifts of two bacterial photosynthetic
      pigments, bacteriochlorophyll (BChl) a and bacteriopheophytin (BPheo) a. Uniform
      stable-isotope labelling strategies were developed and applied to biosynthetic
      preparation of photosynthetic pigments, namely uniformly (13)C, (15)N labelled
      BChl a and BPheo a. Uniform stable-isotope labelling with (13)C, (15)N allowed
      performing the assignment of the (13)C, (15)N and (1)H resonances. The
      photosynthetic pigments were isolated from the biomass of photosynthetic bacteria
      Rhodopseudomonas palustris 17001 grown in uniformly (13)C (99%) and (15)N (98%)
      enriched medium. Both pigments were characterised by NMR in solution (acetone
      d(6)) and by MAS NMR in solid state and their NMR resonances were recorded and
      assigned through standard liquid 2D (13)C-(13)C COSY, (1)H-(13)C HMQC, (1)H-(15)N
      HMBC and solid 2D (13)C-(13)C RFDR, (1)H-(13)C FSLG HETCOR and (1)H-(15)N HETCOR
      correlation techniques at 600 MHz and 750 MHz. The characterisation of pigments
      is of interest from biochemical to pharmaceutical industries, photosynthesis and
      food research.

PMID- 18802971
TI  - Complete NMR spectral assignments of two new iridoid diastereoisomers from the
      flowers of Plumeria rubra L. cv. acutifolia.
AB  - Two new iridoid diastereoisomers (1, 2), together with five known compounds, were
      isolated from the flowers of Plumerian rubra L. cv. acutifolia. Their structures
      were elucidated by the means of in-depth spectroscopic and mass-spectrometric
      analyses, particularly 1D and 2D NMR spectroscopy.

PMID- 18802972
TI  - Stress incontinence.  Surgical treatments for women.

PMID- 18802973
TI  - Inflammatory bowel disease and infection concerns.

PMID- 18802975
TI  - What is mucus? And why is so much produced in your nose when you have a cold?

PMID- 18802974
TI  - Chronic obstructive pulmonary disease.  Steps for better breathing.

PMID- 18802976
TI  - Labeling changes for Reyataz.

PMID- 18802977
TI  - Heat-stable Norvir tablet provides similar drug levels to capsule.

PMID- 18802978
TI  - Women and non-whites new to HAART respond similarly to men and whites.

PMID- 18802979
TI  - Tipranavir effective and well tolerated in children.

PMID- 18802980
TI  - CASTLE data show no gender differences.

PMID- 18802981
TI  - Phase III trial begins for elvitegravir.

PMID- 18802982
TI  - Outbreak of norovirus gastroenteritis at a university student residence-
      Edmonton, Alberta, 2006.

PMID- 18802983
TI  - Investigation of community-associated methicillin-resistant Staphylococcus aureus
      in a remote northern community, Nunavut, Canada.

PMID- 18802984
TI  - Selecting medical students.

PMID- 18802985
TI  - Health services under siege: the case for clinical process redesign.

PMID- 18802986
TI  - Cryptococcus gattii infections on Vancouver Island, British Columbia, Canada:
      emergence of a tropical fungus in a temperate environment.
AB  - BACKGROUND: Cryptococcus gattii causes disease among immunocompetent individuals
      in the tropics and subtropics. We document the appearance of C. gattii infections
      on Vancouver Island (VI), a temperate region, and discuss reasons for this
      emergence. METHODS: Data on Cryptococcus hospitalizations for the calendar years
      1995 through 2004 were reviewed. Viable historic isolates stored at the
      provincial public health laboratory between 1987 and 2000 were serotyped. Human
      cases were mapped by place of residence. RESULTS: Cryptococcosis among HIV
      negative individuals diagnosed on VI increased sharply after 1999. C. gattii was
      not detected in stored isolates prior to 1999. C. gattii cases lived in a
      specific biogeoclimatic zone on VI. Higher rates of illness were associated with
      exposure to the central region of VI. CONCLUSIONS: The emergence of C. gattii in
      a temperate region is unprecedented. Clinicians should consider C. gattii in the
      differential diagnosis of individuals who travelled to certain areas in British
      Columbia.

PMID- 18802987
TI  - Influenza in Canada: 2007-2008 season update.

PMID- 18802988
TI  - Long-term use of progestogens-effects on single organ systems. Proceedings of the
      European Progestin Club scientific meeting. Istanbul, Turkey. June 7, 2006.

PMID- 18802989
TI  - Statement on hepatitis vaccines for travellers. An Advisory Committee Statement
      (ACS).

PMID- 18802990
TI  - Proceedings of a symposium on the chemistry and toxicology of acrylamide. August
      19-23, 2007. Boston, Massachusetts, USA.

PMID- 18802991
TI  - Statement on influenza vaccination for the 2008-2009 season. An Advisory
      Committee Statement (ACS).

PMID- 18802992
TI  - Dental behavioural management problems and dental caries  prevalence in 3- to 6
      year-old Swedish children born preterm.
AB  - BACKGROUND: Today, most children born preterm survive without major impairments.
      But high frequencies of cognitive and behavioural difficulties arise. Studies on
      dental behavioural management problems (DBMP) in these children are lacking. In
      addition, studies on caries prevalence are few and inconclusive. AIM: This study
      aims to compare the frequency of behavioural problems and poor compliance with
      dental treatment in preschool children born preterm with those born full-term.
      The prevalence of caries was also studied. METHODS: The study group included 187
      children born between 23 and 32 weeks of gestation. The control group constituted
      full-term children matched by age, sex, immigrant background, and dental
      operator. DBMP, number of dental visits, missed appointments, and caries between
      ages 3 and 6 were noted. RESULTS: At age 3, but not at age 6, the prevalence of
      DBMP at clinical examinations was significantly higher in preterm children
      compared with the control group. Of the children who received dental treatments
      during preschool years, preterm children displayed significantly more DBMP. No
      significant difference in dental visits or in caries prevalence was found.
      Preterm children, however, missed significantly more dental appointments.
      CONCLUSION: Children born preterm display a higher prevalence of DBMP at dental
      examinations and treatments during preschool years.

PMID- 18802993
TI  - Calculating left ventricular end diastolic pressure from Doppler
      Echocardiography.

PMID- 18802994
TI  - A long-term effect of caries-related factors in initially  caries-free children.
AB  - AIM: The aim of this study was to examine the rate and pattern of early childhood
      caries development in caries-free children based on their dental plaque
      accumulations, salivary Streptococcus mutans levels, maternal sharing, oral
      hygiene, and feeding attitudes at baseline and at 24-month follow-up period.
      DESIGN: A total of 92 children, aged between 15 to 35 months, comprised the study
      group. The children's dental examinations were first carried out at baseline, and
      56 of them were re-examined 24 months later to determine the changes in dental
      status. The mothers were also interviewed at each examination based on a prepared
      questionnaire. RESULTS: The prevalence of caries incidence was 45% at 24-month
      evaluation period among initially caries-free children. The new caries formation
      was mostly observed on occlusal and aproximal surfaces of maxillary molars (28%
      and 26%) followed by mesial, distal and buccal surfaces of anterior teeth,
      respectively. Significant correlations between dental caries formation and
      maternal sharing, S. mutans levels, and plaque scores were found. CONCLUSION: The
      results indicated that early S. mutans colonization, high plaque accumulation,
      and maternal sharing were important factors on a child's caries development.

PMID- 18802995
TI  - Is it possible to determine a 'powerful marker of health'?

PMID- 18802996
TI  - The usefulness of a perfect parasite.

PMID- 18802997
TI  - Can calprotectin predict relapse risk in inflammatory bowel disease?
AB  - OBJECTIVE: Assessing the clinical course of inflammatory bowel disease (IBD)
      patients consists of periodical clinical evaluations and laboratory tests. We
      aimed to assess the role of calprotectin tests in predicting clinical relapse in
      IBD patients. METHODS: Ninety-seven patients with ulcerative colitis (UC) and 65
      with Crohn's disease (CD) in clinical remission were prospectively included in
      the study. A 10-g stool sample was collected for calprotectin assay. The cutoff
      level was set at 130 mg/kg of feces. Patients were followed up for 1 yr after the
      test or until relapse. The cumulative proportion of relapses was estimated by the
      Kaplan-Meier analysis. Statistics for equality of survival distribution were
      tested using the log-rank test. RESULTS: The calprotectin test was positive in 44
      UC patients and 26 of them relapsed within a year, while 11 of 53 UC patients
      with a negative calprotectin test relapsed within the same time frame. Thirty CD
      patients had a positive calprotectin test and 13 of them relapsed within a year,
      as did 7 of the 35 with a negative test result. A significant correlation emerged
      between a positive calprotectin test and the probability of relapse in UC
      patients (P= 0.000). In CD patients, only cases of colonic CD showed a
      significant correlation between a positive calprotectin test and the probability
      of relapse, i.e., 6 colonic CD patients were positive for the calprotectin test
      and 4 relapsed (P= 0.02). CONCLUSIONS: Measuring calprotectin may help to
      identify UC and colonic CD patients at higher risk of clinical relapse.

PMID- 18802998
TI  - Small intestinal bacterial overgrowth recurrence after antibiotic therapy.
AB  - OBJECTIVES: Current treatment for small intestinal bacterial overgrowth (SIBO) is
      based on courses of broad-spectrum antibiotics. No data concerning SIBO
      recurrence are available. The aims of the present study were to investigate SIBO
      recurrence as assessed by glucose breath test (GBT) after antibiotic treatment
      and conditions associated to SIBO recurrence. METHODS: Eighty consecutive
      patients affected by SIBO and decontaminated by rifaximin (1,200 mg per day for 1
      wk) were enrolled. Diagnosis of SIBO was based on GBT. GBT was reassessed at 3,
      6, and 9 months after evidence of GBT normalization. GBT positivity recurrence,
      predisposing conditions, and gastrointestinal symptoms were evaluated. RESULTS:
      Ten (10/80, 12.6%), 22 (22/80, 27.5%), and 35 (35/80, 43.7%) patients showed
      positivity to GBT at 3, 6, and 9 months after successful antibiotic treatment,
      respectively. At multivariate analysis, older age (OR 1.09, 95% CI 1.02-1.16),
      history of appendectomy (OR 5.9, 95% CI 1.45-24.19), and chronic use of proton
      pump inhibitors (PPIs) (OR 3.52, 95% CI 1.07-11.64) were significantly associated
      to GBT positivity recurrence. All gastrointestinal symptoms significantly
      increased at 3, 6, and 9 months in patients with evidence of GBT positivity
      recurrence. CONCLUSIONS: GBT positivity recurrence rate was high after antibiotic
      treatment. Older age, history of appendectomy, and chronic use of PPIs were
      associated with GBT positivity recurrence. Patients with evidence of GBT
      positivity recurrence showed gastrointestinal symptoms relapse thus suggesting
      SIBO recurrence.

PMID- 18802999
TI  - Intestinal gas and bloating: effect of prokinetic stimulation.
AB  - BACKGROUND: It is unknown if abdominal bloating is attributable to excess
      abdominal gas or improved by a prokinetic agent. AIMS: To assess abdominal gas
      content in functional abdominal bloating and to ascertain the effect of a
      prokinetic agent on intestinal gas symptoms in these patients. METHODS: In 20
      patients, intra-abdominal gas content and symptoms were quantified before and
      during treatment with pyridostigmine (30 mg/8 hp. o) in this randomized, placebo
      controlled, double-blind study. Daily symptoms were quantified for 5 days before
      and 10 days during treatment, and abdominal gas volume was quantified by CT
      imaging before and at the fourth day of treatment. A CT scan was also obtained in
      10 healthy subjects. RESULTS: Before treatment, the total volume of intestinal
      gas was similar in patients (112 +/- 18 mL) and in healthy controls (116 +/- 20
      mL). The treatment-induced change in total and regional intestinal gas volume was
      not significantly different between pyridostigmine (-4 +/- 18 mL; mean +/- SEM)
      and placebo (0 +/- 15 mL). However, pyridostigmine reduced the severity of
      bloating from 3.3 +/- 0.3 to 2.6 +/- 0.4 (P < 0.05), whereas placebo did not (3.2
      +/- 0.3 vs 3.0 +/- 0.4), although the change did not reach statistical difference
      across groups. CONCLUSION: In patients complaining of functional bloating, the
      volume and distribution of intestinal gas, measured on nonselected days, is
      comparable to asymptomatic subjects. Prokinetic stimulation improves bloating
      sensation without detectable changes in gas content.

PMID- 18803001
TI  - Characterization of the amylovorin locus of Lactobacillus amylovorus DCE 471,
      producer of a bacteriocin active against Pseudomonas aeruginosa, in combination
      with colistin and pyocins.
AB  - Lactobacillus amylovorus DCE 471 produces amylovorin L, a bacteriocin with an
      antibacterial activity against some strains of the Lactobacillus lineage. Based
      on the sequence of one active peptide, a gene encoding active amylovorin L was
      cloned and sequenced. Genome walking allowed us to sequence a larger fragment of
      7577 bp of genomic DNA, with 12 predicted ORFs. The previously characterized
      amylovorin L peptide-encoding gene is preceded by another gene encoding a small
      polypeptide with a typical bacteriocin-processing double-glycine site, suggesting
      that amylovorin L is a two-component class IIb bacteriocin (amylovorin
      Lalpha/beta). Lalpha and Lbeta show the highest similarity to gassericin T from
      Lactobacillus gasseri SBT2055 and BlpN from Streptococcus pneumoniae R6,
      respectively, and to LafA and LafX, which form the lactacin F bacteriocin of
      Lactobacillus johnsonii NCC 533. As for other lactic acid bacteria bacteriocins,
      amylovorin L showed no activity against the Gram-negative opportunistic pathogen
      Pseudomonas aeruginosa on its own, but showed synergistic inhibitory activity
      when used in combination with the peptide antibiotic colistin, and, remarkably,
      with the P. aeruginosa soluble bacteriocins, pyocins S1 and S2.

PMID- 18803000
TI  - Effects of amitriptyline on gastric sensorimotor function and postprandial
      symptoms in healthy individuals: a randomized, double-blind, placebo-controlled
      trial.
AB  - BACKGROUND: Low-dose tricyclic antidepressants have been used to treat chronic
      somatic and gastrointestinal pain disorders, including refractory functional
      dyspepsia. However, there are only limited data on the effects of these drugs on
      upper gastrointestinal function. AIM: To compare the effects of two doses of
      amitriptyline (AMT) and placebo on gastric accommodation, emptying, satiation,
      and postprandial symptoms in healthy volunteers. METHODS: Using a parallel-group,
      double-blind, placebo-controlled design, 41 healthy volunteers were randomized to
      AMT 25 mg, AMT 50 mg, or placebo for 2 wk. During the final 3 days of therapy,
      the following end points were assessed: fasting and postprandial gastric volumes,
      2- and 4-h gastric emptying, time and volume to maximum satiation using a
      nutrient drink test, and postprandial symptoms 30 min later using 10-cm visual
      analog scales. AMT and metabolite levels were measured. RESULTS: AMT slowed
      gastric emptying at 2 h (median 75% for placebo, 57% for AMT 25 mg, 67% for AMT
      50 mg; P= 0.037) and 4 h (median 98% for placebo, 96% for AMT 25 mg, 92% for AMT
      50 mg; P= 0.003). AMT did not affect gastric volumes or satiation volume, but it
      did reduce nausea scores at 30 min in a dose-dependent manner (median 2.1 for
      placebo, 0.9 for AMT 25 mg, and 0.0 for AMT 50 mg; P= 0.009). CONCLUSION: In
      healthy volunteers, AMT slows gastric emptying of solids, but it does not
      significantly affect gastric volumes or satiation. AMT reduces nausea after
      challenge with a high calorie liquid load.

PMID- 18803002
TI  - Still making their ascent. Disclosure rules don't hinder CEOs from big paydays,
      perks, as salaries for top-level healthcare execs rose 4% for 2007.
AB  - A tight economy and stricter disclosure rules on CEO compensation don't seem to
      have tamped down the trend for extravagant paydays. Eleven of the 30 CEOs in
      Modern Healthcare's annual report on executive pay made $10 million or more. But
      not everything was up. "Incentive payouts, as a percentage of opportunities, have
      dropped from five years ago," says consultant Jim Nelson, left.

PMID- 18803003
TI  - IT bill draws concerns. Industry leery over pay, privacy, security matters.

PMID- 18803004
TI  - AHLTA under attack. EHR system stays despite blog complaints: Defense.

PMID- 18803005
TI  - CoxHealth settles. System denies wrongdoing on false claims charges.

PMID- 18803006
TI  - Docs, integrated go at it again. Calif. physician network files two new lawsuits.

PMID- 18803007
TI  - By the numbers. Most frequently billed Medicare drugs. Ranked by 2006 Medicare
      patient discharges.

PMID- 18803008
TI  - Web of power. Information and technology are changing the face of healthcare and
      its leadership, according to this year's 7th annual 100 Most Powerful People in
      Healthcare ranking.
AB  - The Internet and technology helped catapult this year's No. 1 to the top of the
      Most Powerful People in Healthcare roster, along with the No. 2 and No. 3 picks.
      But politicians also had a good showing in the top 10, including presidential
      candidates Barack Obama and John McCain, and ailing Democratic lion, Sen. Edward
      Kennedy, left.

PMID- 18803009
TI  - Coverage no panacea: study. Survey finds insured have trouble paying bills, too.

PMID- 18803010
TI  - Harry and Louise, part two. Faux couple return, but sequel pushes reform.

PMID- 18803011
TI  - Horizon's stormy skies. Latest bid for conversion sure to meet opposition.

PMID- 18803012
TI  - Revisions to Form 990 complete.

PMID- 18803013
TI  - Ready or not...HHS prepares for ICD-10; some say not so fast.

PMID- 18803014
TI  - Associations: FAH sees 4.9% net income rise.

PMID- 18803015
TI  - The do-it-yourselfers. Some docs studying to help develop devices.

PMID- 18803016
TI  - Effect of transforming growth factor-alpha on enterocyte apoptosis is correlated
      with EGF receptor expression along the villus-crypt axis during methotrexate
      induced intestinal mucositis in a rat.
AB  - The purpose of the present study was to evaluate the effect of transforming
      growth factor-alpha (TGF-alpha) on enterocyte apoptosis following methotrexate
      (MTX) induced intestinal mucositis in a rat and in Caco-2 cells. Non-pretreated
      and pretreated with MTX Caco-2 cells were incubated with increasing
      concentrations of TGF-alpha. Cell apoptosis was determined by FACS cytometry.
      Adult rats were divided into four groups: Control, Control-TGF-alpha, MTX, and
      MTX- TGF-alpha rats. Three days later rats were sacrificed. Enterocyte apoptosis
      were measured at sacrifice. RT-PCR and Western Blotting was used to determine the
      level of Bax and Bcl-2 mRNA and protein. Real time PCR was used to measure
      epidermal growth factor receptor (EGFr) expression along the villus-crypt axis.
      The in vitro experiment has shown that treatment with TGF-alpha of Caco-2 cells
      results in a significant inhibition of cell apoptosis in a dose-dependent manner.
      In vivo experiment, a decreased levels of apoptosis in MTX- TGF-alpha rats
      corresponded with the decrease in Bax and with the increase in Bcl-2 at both mRNA
      and protein levels. The inhibiting effect of TGF-alpha on enterocyte apoptosis
      was strongly correlated with EGFr expression along the villus-crypt axis. In
      conclusion, treatment with TGF-alpha inhibits enterocyte apoptosis following MTX-
      injury in the rat.

PMID- 18803017
TI  - Ethics training needs to emphasize disclosure and apology.

PMID- 18803018
TI  - Safety in human research: past problems and current challenges from a Canadian
      perspective.

PMID- 18803019
TI  - Pharmacists and health information technology: emerging issues in patient safety.

PMID- 18803020
TI  - Ethical and legal issues in the use of health information technology to improve
      patient safety.

PMID- 18803021
TI  - Proportionality and the view from below: analysis of error disclosure.

PMID- 18803022
TI  - Problematic medical errors and their implications for disclosure.

PMID- 18803023
TI  - Characterising functionally important and ecologically meaningful genetic
      diversity using a candidate gene approach.
AB  - Over the past two decades the fields of molecular ecology and population genetics
      have been dominated by the use of putatively neutral DNA markers, primarily to
      resolve spatio-temporal patterns of genetic variation to inform our understanding
      of population structure, gene flow and pedigree. Recent emphasis in comparative
      functional genomics, however, has fuelled a resurgence of interest in
      functionally important genetic variation that underpins phenotypic traits of
      adaptive or ecological significance. It may prove a major challenge to transfer
      genomics information from classical model species to examine functional diversity
      in non-model species in natural populations, but already multiple gene-targeted
      candidate loci with major effect on phenotype and fitness have been identified.
      Here we briefly describe some of the research strategies used for isolating and
      characterising functional genetic diversity at candidate gene-targeted loci, and
      illustrate the efficacy of some of these approaches using our own studies on red
      grouse (Lagopus lagopus scoticus). We then review how candidate gene markers have
      been used to: (1) quantify genetic diversity among populations to identify those
      depauperate in genetic diversity and requiring specific management action; (2)
      identify the strength and mode of selection operating on individuals within
      natural populations; and (3) understand direct mechanistic links between allelic
      variation at single genes and variance in individual fitness.

PMID- 18803024
TI  - Isolation of a Xanthobacter sp. degrading dichloromethane and characterization of
      the gene involved in the degradation.
AB  - A bacterial strain able to degrade dichloromethane (DCM) as the sole carbon
      source was isolated from a wastewater treatment plant receiving domestic and
      pharmaceutical effluent. 16S rDNA studies revealed the strain to be a
      Xanthobacter sp. (strain TM1). The new isolated strain when grown aerobically on
      DCM showed Luong type growth kinetics, with 1(max) of 0.094 h(-1) and S (m) of
      1,435 mg l(-1). Strain TM1 was able to degrade other aromatic and aliphatic
      halogenated compounds, such as halobenzoates, 2-chloroethanol and dichloroethane.
      The gene for DCM dehalogenase, which is the key enzyme in DCM degradation, was
      amplified through PCR reactions. Strain TM1 contains type A DCM dehalogenase
      (dcmAa), while no product could be obtained for type B dehalogense (dcmAb). The
      sequence was compared against 12 dcmAa from other DCM degrading strains and 98%
      or 99% similarity was observed with all other previously isolated DCM
      dehalogenase genes. This is the first time a Xanthobacter sp. is reported to
      degrade DCM.

PMID- 18803025
TI  - A comparative study of methanol as a supplementary carbon source for enhancing
      denitrification in primary and secondary anoxic zones.
AB  - A comparative study on the use of methanol as a supplementary carbon source to
      enhance denitrification in primary and secondary anoxic zones is reported. Three
      lab-scale sequencing batch reactors (SBR) were operated to achieve nitrogen and
      carbon removal from domestic wastewater. Methanol was added to the primary anoxic
      period of the first SBR, and to the secondary anoxic period of the second SBR. No
      methanol was added to the third SBR, which served as a control. The extent of
      improvement on the denitrification performance was found to be dependent on the
      reactor configuration. Addition to the secondary anoxic period is more effective
      when very low effluent nitrate levels are to be achieved and hence requires a
      relatively large amount of methanol. Adding a small amount of methanol to the
      secondary anoxic period may cause nitrite accumulation, which does not improve
      overall nitrogen removal. In the latter case, methanol should be added to the
      primary anoxic period. The addition of methanol can also improve biological
      phosphorus removal by creating anaerobic conditions and increasing the
      availability of organic carbon in wastewater for polyphosphate accumulating
      organisms. This potentially provides a cost-effective approach to phosphorus
      removal from wastewater with a low carbon content. New fluorescence in situ
      hybridisation (FISH) probes targeting methanol-utilising denitrifiers were
      designed using stable isotope probing. Microbial structure analysis of the
      sludges using the new and existing FISH probes clearly showed that the addition
      of methanol stimulated the growth of specific methanol-utilizing denitrifiers,
      which improved the capability of sludge to use methanol and ethanol for
      denitrification, but reduced its capability to use wastewater COD for
      denitrification. Unlike acetate, long-term application of methanol has no
      negative impact on the settling properties of the sludge.

PMID- 18803026
TI  - Survey of natural enemies of spider mites (Acari: Tetranychidae) in citrus
      orchards in eastern Spain.
AB  - Field surveys were conducted from 2004 to 2007 to determine the species
      composition and relative abundance of natural enemies associated with colonies of
      either the citrus red mite, Panonychus citri, or the two spotted spider mite,
      Tetranychus urticae, in Valencian citrus orchards (eastern Spain). Fourteen
      species were recorded, six phytoseiid mites and eight insect predators. Two of
      them are reported for the first time on citrus in Spain and two more are first
      reports as predators associated with T. urticae. The community of predators
      associated with T. urticae and P. citri was almost identical, and the Morisita
      Horn index of similarity between both natural enemy complexes was close to one,
      suggesting that predators forage on both pest species. Quantifying the presence
      of many known spider mites predators in Valencian citrus orchards is an important
      first step towards spider mite control. A challenge for future studies will be to
      establish conservation and/or augmentation management strategies for these
      predators, especially to improve T. urticae biological control.

PMID- 18803027
TI  - Cell junctions in fish seminiferous epithelium.
AB  - Similar to mammals, in fish the cellular interactions between Sertoli cells (SC)
      and germ cells (GC) in the seminiferous epithelium have important structural and
      functional roles. In this review, we give a brief summary of these interactions,
      in particular those on the cell junctions. Despite the scarcity of detailed
      empirical data, it appears that both basic types of adhesive junctions (actin-
      and intermediate filaments-related) are present between SC. However, the actin
      related multifunctional junction known as the "ectoplasmic specialization" is
      seemingly present only in some cartilaginous fish. Conversely, SC in other fish
      species are joined by actin-related junctions similar to typical zonulae or
      puncta adherens found in other epithelia. Adhesive junctions are also found
      between SC and GC and between GC and GC, and due to their particular
      characteristics these junctions are known as "desmosome-like junctions". In terms
      of intercellular communication, connexins and gap junctions have been shown to
      occur between SC in fish, and they may be involved in the coordination of the
      synchronous development of GC within the cysts. It is also possible that gap
      junctions may form an interconnected network between SC and GC within a cyst.
      Concerning the SC barrier, tight junctions between fish SC apparently form a
      functional barrier only in cysts containing haploid GC, and different from
      mammals, meiotic GC in fish are not shielded from the vascular system. In
      summary, although still not well investigated, cell-cell interactions in the
      seminiferous epithelium of fish seem to be crucial for GC development, and their
      disturbance, for example by changing environmental conditions, will probably
      affect GC survival and fertility.

PMID- 18803029
TI  - The use of gyrB sequence analysis in the phylogeny of the genus Amycolatopsis.
AB  - Partial gyrB sequences (>1 kb) were obtained from 34 type strains of the genus
      Amycolatopsis. Phylogenetic trees were constructed to determine the effectiveness
      of using this gene to predict taxonomic relationships within the genus. The use
      of gyrB sequence analysis as an alternative to DNA-DNA hybridization was also
      assessed for distinguishing closely related species. The gyrB based phylogeny
      mostly confirmed the conventional 16S rRNA gene-based phylogeny and thus provides
      additional support for certain of these 16S rRNA gene-based phylogenetic
      groupings. Although pairwise gyrB sequence similarity cannot be used to predict
      the DNA relatedness between type strains, the gyrB genetic distance can be used
      as a means to assess quickly whether an isolate is likely to represent a new
      species in the genus Amycolatopsis. In particular a genetic distance of >0.02
      between two Amycolatopsis strains (based on a 315 bp variable region of the gyrB
      gene) is proposed to provide a good indication that they belong to different
      species (and that polyphasic taxonomic characterization of the unknown strain is
      worth undertaking).

PMID- 18803028
TI  - Effect of different level and source of copper supplementation on immune response
      and copper dependent enzyme activity in lambs.
AB  - An experiment was conducted on 30 male Nellore lambs with average body weight
      (BW) of 15.45 +/- 0.06 kg to determine the level of the copper (Cu)
      supplementation in diet from inorganic and organic sources required for optimum
      immunity and its effect on copper dependent enzymes by allotting them randomly to
      five groups in completely randomized design. The dietary treatments were viz.,
      basal diet (no Cu supplementation, BD), other four groups were offered BD
      supplemented with 7 or 14 ppm Cu from copper sulphate (CuSO(4)) and Cu
      proteinate, respectively. The lambs were fed the respective diets at 3.5 per cent
      BW to meet the requirements except Cu for 180 days. The humoral immune response
      against Brucella abortus and chicken RBC was assessed after 90 days of feeding.
      The in vivo delayed type hyper sensitivity reaction against PHA-P and in vitro
      lymphocyte proliferation against Con A indicative of cell mediated immune
      response (CMI) was assayed at 180 days of feeding. At the end of experiment four
      lambs from each group were slaughtered for estimation of liver superoxide
      dismutase activity (SOD). The ceruloplasmin and RBC-SOD activities were higher (P
      < 0.05) in 14 ppm Cu supplemented lambs from Cu-proteinate at 90 and 180 days,
      while the liver SOD activity was higher (P < 0.05) in lambs fed 14 ppm Cu from
      CuSO(4). The STAT titres against B. abortus were higher in Cu supplemented lambs,
      with no effect of dose of supplementation. Lambs supplemented with Cu-proteinate
      had higher titers than CuSO(4) on 7 and 14 days of post sensitization. The total
      immunoglobulin concentration and the CMI response against PHA-P and Con-A was
      higher (P < 0.05) in lambs fed 14 ppm Cu-proteinae diet. The IgM level was though
      high in Cu supplemented lambs, no dose or source effect were observed. The study
      indicated that Cu dependent enzymes activity and immune response were highest and
      respond better against stress in lambs on 14 ppm supplemented Cu from Cu
      proteinate.

PMID- 18803030
TI  - Vancomycin vs teicoplanin in the treatment of Gram-positive infections: a
      pharmacoeconomic analysis in a Turkish University Hospital.
AB  - OBJECTIVE: The aim of this study was to estimate and compare the costs of
      vancomycin and teicoplanin in the treatment of Gram-positive hospital infections
      in Turkey using a cost minimisation analysis. SETTING: Hacettepe University
      Hospital, Ankara, Turkey. METHOD: The health-care provider's perspective was
      considered within formal pharmacoeconomic assessment methodology. The records of
      76 patients who had been hospitalised and treated for Gram-positive infections at
      Hacettepe University Hospital between 16 July 2003 and 22 November 2003 were
      retrospectively evaluated to obtain individual data on resources and associated
      costs. MAIN OUTCOME MEASURE: From a cost minimisation perspective, hospital
      directors may consider teicoplanin to be a relevant option in addition to
      vancomycin. RESULT: The estimated mean treatment cost per patient was 1,780 TRY
      (1,101 EUR) for teicoplanin and 1,429 TRY (884 EUR) for vancomycin, with
      statistical analysis failing to reveal any significant difference between the two
      drugs in terms of these total costs (p = 0.33). This cost minimisation analysis
      shows that the average costs of vancomycin and teicoplanin per patient observed
      did not differ significantly. CONCLUSION: Other potential advantages of one drug
      over the other, as reported by other authors, such as differing safety profiles
      or advantages in administration, may ultimately decide which is preferred.

PMID- 18803031
TI  - Bipolar disorder associated to substance use disorders (dual diagnosis).
      Systematic review of the scientific evidence and expert consensus.
AB  - The present work focuses on the so-called dual diagnosis (DD): bipolar disorder
      (BD) associated with substance use disorders (SUD). Although the psychiatrists
      who treat patients with BD and physicians in charge of patients with SUD
      frequently find this association with DD, unfortunately there are few scientific
      works that have studied this association. The Spanish Working Group on Bipolar
      Disorders in Dual Diagnosis reviewed the published material using a Medline
      search and selected the most relevant articles. Following this, the Work Group
      developed an expert consensus in DD and finally, a survey was performed among a
      group of experts in this disorder to cover the areas that were not fully
      addressed by the scientific evidence or in those areas in which the Work Group
      was unable to reach a consensus. We conclude that, in view of the above,
      establishment of a consensus is a valid tool to complement the current scientific
      evidence.

PMID- 18803032
TI  - [Meteorological factors and psychiatric emergencies].
AB  - INTRODUCTION: Studies conducted in the psychiatric setting and related with
      biometeorology generally coincide that there is a seasonal rhythm between seasons
      and depressive disorders, violent suicides and manic episodes. However, there are
      many discrepancies about the correlation of specific meteorological variables
      with the remaining clinical pictures. This work has aimed to study a wide sample
      of psychiatric cases in this area (Baix Camp/Tarragona) to see whether there is a
      relationship between meteorological variables and the total number of daily
      emergencies. METHOD: We recorded the data of 3,048 cases attended in the
      Emergency Department of the Hospital Pere Mata de Reus (Tarragona) from January
      1, 2003 to December 31, 2005. The possible relationship between the number of
      daily visits and different meteorological endpoints (such as wind direction and
      speed, temperature, humidity, atmospheric pressure and solar radiation) were
      analyzed statistically. RESULTS: The results were statistically significant for
      the meteorological endpoints of medium temperature (TMED), maximum temperature
      (TMAX) and minimum temperature (TMIN). The relationship between humidity and
      number of daily visits was also statistically significant (non-linear form). The
      remaining comparisons did not reach statistical significance. CONCLUSIONS: The
      main conclusion of our study is that there is a direct relationship between
      environmental temperature increase and the number of patients attended in the
      hospital emergency department. A relationship could also be observed in regards
      to humidity. This fact may suggest the need to have suitable medical attendance
      planning for the hottest and most humid periods.

PMID- 18803033
TI  - Stem cell research in Switzerland.

PMID- 18803034
TI  - The role of inflammation, humoral and cell mediated autoimmunity in the
      pathogenesis of atherosclerosis.
AB  - The pathogenesis of atherosclerosis has not been well defined and many questions
      remain unanswered. Many studies have discussed the importance of inflammation as
      the first step in promoting endothelial dysfunction and atherosclerosis.The
      association of inflammatory markers such as fibrinogen and C reactive protein
      (CRP) with atherosclerosis and cardiovascular/cerebrovascular clinical events
      reinforces the pivotal role that inflammation plays in the atherosclerotic
      process.The humoral and cellular autoimmune response against antigens expressed
      in the endothelium and the greater prevalence of atherosclerosis in immune
      mediated rheumatic diseases such as Rheumatoid Arthritis (RA) and Systemic Lupus
      Erythematosus (SLE) strongly suggest the involvement of autoimmunity in the
      atherosclerotic process. The role of inflammation and autoimmune responses in
      atherosclerosis are discussed in order to better understand their close link on
      its pathogenesis.

PMID- 18803035
TI  - Derivation of the first Swiss human embryonic stem cell line from a single
      blastomere of an arrested four-cell stage embryo.
AB  - PRINCIPLES: Human embryonic stem cells (hESC) hold enormous potential for
      regenerative medicine. So far, the majority of hESC lines have been derived from
      the isolated inner cell mass (ICM) of blastocysts of variable quality, and
      several of them from low-grade embryos. Moreover, most of the lines have been
      obtained in media containing animal components such as foetal bovine serum. We
      aimed to derive hESC lines in xeno-free conditions using spare embryos frozen in
      Switzerland before 2001. METHODS: In cooperation with Swiss IVF centres we
      collected up to 199 donated embryos frozen between 1988 and 2000 at different
      stages of development. RESULTS: Embryo quality at thawing showed wide
      variability, reduced quality and low survival upon culture. Using early arrested
      embryos (n=46), we report here the first Swiss hESC line, called CH-ES1, derived
      from a single blastomere of an arrested four-cell-stage embryo. Despite its
      polyploidy, already present at the third passage, CH-ES1 expressed ESC markers of
      pluripotency and differentiated into all three germ layers in embryoid bodies in
      vitro and in teratomas in vivo. CONCLUSIONS: As the destruction of viable
      developing embryos, even spare ones, raises serious ethical concerns, deriving
      hESC lines from arrested embryos may be an alternative approach to avoid embryo
      destruction. However, given the reduced derivation efficiency they should not be
      considered a unique and/or selective source of hESC lines.

PMID- 18803036
TI  - A challenged choice: donating spare embryos to stem cell research in Switzerland.
AB  - RESEARCH QUESTIONS: Couples undergoing IVF in Switzerland may have embryos in
      excess of their clinical need that they can donate to human embryonic stem cell
      research. Thus a new practice has emerged in Switzerland when IVF treatment and
      embryonic stem cell research come into contact. This interface needs to be
      investigated from an ethical-legal point of view to facilitate a fair informed
      choice process for the couples involved. METHODS: Ethical analysis, patient
      perspectives elaboration. Interdisciplinary approach that draws on the research
      project JESP-ELSI (joint embryonic stem cell research project--ethical legal and
      societal implications). RESULTS AND CONCLUSIONS: To facilitate the donation of
      surplus embryos to human embryonic stem cell research, we propose a procedure of
      informed choice that fits to the current Swiss legal situation. In addition we
      identify problems within the current legal setting and suggest methods to improve
      communication at the interface between IVF and embryonic stem cell research from
      an ethical perspective.

PMID- 18803037
TI  - Diagnostic accuracy of exercise electrocardiogram in patients with left anterior
      hemi-block.
AB  - BACKGROUND: Left anterior hemiblock (LAHB) is the most frequent conduction
      abnormality, but its impact on the diagnostic accuracy of the exercise ECG has
      not been studied. The aim of our study was to determine the diagnostic accuracy
      of ST depression for predicting ischaemia in the presence of LAHB. PATIENTS:
      Consecutive patients with known or suspected coronary heart disease undergoing
      exercise ECG and 99mTc-sestamibi single photon emission computed tomography
      (SPECT) were included in the analysis. Patients with left bundle branch block,
      with changes in QRS morphology related to myocardial infarction, and patients who
      had undergone pharmacological stress testing were excluded. RESULTS: Of 1532
      patients assessed, 567 patients qualified for the analysis. In 69 patients with
      LAHB, ECG stress testing had lower sensitivity (38% vs 86%) and lower negative
      predictive value (82% vs 92%) than in patients with normal baseline ECG. The
      reduction of sensitivity appeared to be similar in patients with isolated LAHB
      (n=43), in patients with right bundle branch block (n=39), and with bifascicular
      block (n=26). In contrast, the positive predictive value of the test was
      excellent. CONCLUSION: The diagnostic accuracy of the exercise ECG for prediction
      of ischaemia is reduced in patients with LAHB.

PMID- 18803038
TI  - [Safety and feasibility of laparoscopic surgery and open surgery in ulcerative
      colitis: a meta-analysis].
AB  - OBJECTIVE: To compare the safety and feasibility of laparoscopic surgery and open
      surgery in ulcerative colitis. METHODS: A search of published studies in English
      and Chinese between January 1992 and May 2008 was performed. Nine hundred and
      twenty-three patients from 16 studies were recruited which met the inclusion
      criteria. Meta-analysis was performed through fixed effect model or random effect
      model dependent on heterogeneity. RESULTS: Compared to open procedure, patients
      with ulcerative colitis undergone laparoscopic surgery were able to tolerate oral
      intake significantly earlier (P<0.01) with shorter hospital stay (P<0.01) and had
      lower total complication rate (P<0.01). But duration of laparoscopic surgery was
      significantly longer than that of open procedure(P=0.04). Laparoscopic procedure
      was no more superior to open procedure in recovery of bowel function, re
      operation rate, intra-abdominal abscess, anastomotic leak, postoperative bowel
      obstruction, wound infection, blood loss and mortality. The conversion rate was
      4.2% in this analysis. CONCLUSION: Laparoscopic surgery for ulcerative colitis is
      safe and feasible with better recovery in short-term as compared to the open
      procedure.

PMID- 18803039
TI  - [Laparoscopic versus conventional open resection for colorectal cancer: a meta
      analysis on recurrence].
AB  - OBJECTIVE: To compare the recurrence between laparoscopic resection and
      conventional open resection for colorectal cancer with meta-analysis. METHODS:
      Eligible articles were identified by searches of MEDLINE, EMBASE and the Cochrane
      database between January 1991 and January 2007 using the terms (laparoscopy,
      surgery, minimal invasive, colon, intestine, large, colectomy, colonic neoplasms,
      rectal neoplasms and randomized controlled trial). Prospective randomized
      clinical trials were eligible if they included patients with colorectal cancer
      treated by laparoscopic surgery versus open surgery followed-up by recurrence.
      Data were extracted from these trials by three independent reviewers. RESULTS:
      Ten trials with recurrence information of 2474 patients were involved. In the
      combined results, no significant difference in the OR for overall recurrence
      between the laparoscopic surgery and open surgery group was found (OR 0.95, 95%CI
      0.76 to 1.19, P=0.64). Stratified by recurrence type, the combined results of the
      individual reports showed no significant differences for local recurrence (OR
      0.79, 95%CI 0.50 to 1.25,P=0.32), distant metastasis (OR 0.89, 95%CI 0.62 to
      1.28, P=0.54) and port-site or wound-site recurrence (OR 1.04,95%CI 0.21 to
      5.27,P=0.96) between the two surgical techniques. CONCLUSION: The recurrence
      rates for patients with colorectal cancer treated by laparoscopic surgery do not
      differ significantly from those by open surgery. Longer follow up studies will
      further define outcomes comparing the two techniques in the treatment of
      colorectal cancer.

PMID- 18803040
TI  - [Long-term efficacy of endoscopic excision of rectal carcinoids].
AB  - OBJECTIVE: To evaluate the long-term efficacy of endoscopic excision for rectal
      carcinoids. METHODS: Clinical data of 91 patients with rectal carcinoids treated
      by endoscopic excision from 2000 to 2007 were analyzed retrospectively. RESULTS:
      The average size of the primary tumor was 0.8 cm(range 0.3 to 2.3 cm). All the
      tumors were localized within the submucosal layer showing typical histology
      without lymphatic or vessel infiltration. Follow-up was available for 80 patients
      with mean 32.5 months (range 6 to 96 months). There was no recurrence in 65
      patients with tumor size < 1.0 cm. Recurrence occurred in 3 cases among 25
      patients with tumor size from 1.0 to 2.0 cm, and 1 died of hepatic metastasis.
      The 1-, 3-, and 5-year survival rates of the patients were 100%, 98.0%, and 91.4%
      respectively. CONCLUSIONS: Tumor size and depth of invasion are two important
      prognostic factors of rectal carcinoids. Endoscopic excision is useful for rectal
      carcinoid patients with tumor size < 1.0 cm and located within the submucosal
      layer.

PMID- 18803041
TI  - [Clinical study on the alimentary canal reconstruction of uncutted Roux-en-Y with
      jejunal pouch for total gastrectomy].
AB  - OBJECTIVE: To investigate the efficacy of uncutted Roux-en-Y esophagojejunostomy
      with jejunal pouch (URYJP) after total gastrectomy. METHODS: Total gastrectomy
      was performed on 168 patients of gastric cancer, and 3 methods were used for
      reconstruction: the uncutted Roux-en-Y esophagojejunostomy with a jejunal pouch
      was performed on 69 patients(group A),Roux-en-Y esophagojejunostomy with the P
      type jejunal pouch on 50 patients(group B),and Roux-en-Y esophagojejunostomy with
      the Orr-type jejunal pouch on 49 patients (group C). The alimentary tract
      reconstruction time, morbidity and mortality were compared. The 121 cases that
      survived for more than 1 year were analyzed for quality of life(QOL),including
      body weight, intake quantity, prognosis nutritional index (PNI), and Visick
      scores 6 and 12 months after the operations. RESULTS: All the patients recovered
      quickly and no anastomosis leakage or duodenal fistulas were found. It took (30+/
      7) minutes to finish the reconstruction in group A, which was significantly
      shorter than that in group B [(57+/-6) minutes] or in group C [(48+/-6) minutes].
      There were no significant differences among 3 groups in the incidence of alkaline
      reflux gastritis. The incidence of Roux stasis syndrome was 2.2% in group A,
      which was significantly lower than 17.9% and 19.4% in group B and C. Weight loss
      and food intake gain in group A was superior to those in group B and C 6 months
      and 12 months postoperatively. As compared with prognosis nutritional index(PNI)
      postoperatively, those of 3 groups decreased significantly 6 months
      postoperatively. At 12 months after operation, the PNI of group A returned to the
      level before operation, while PNI of both group B and C remained significantly
      lower than those before operation (both P < 0.05). The Visick score of group A
      was superior to those of group B and C 6 months and 12 months postoperatively.
      CONCLUSIONS: The new uncutted Roux operation with jejunal pouch can prevent
      alkaline reflux gastritis and Roux-en-Y stasis syndrome. It may be a standard
      procedure for reconstruction after total gastrectomy.

PMID- 18803042
TI  - [Arteriovenous neoadjuvant FLEOX chemotherapy with nutritional support improves
      the resectable rate for advanced gastric cancer].
AB  - OBJECTIVE: To summarize the resectable rate of advanced gastric cancer
      characterized by abdominal lymph node metastases with the arteriovenous
      neoadjuvant FLEOX chemotherapy plus appropriate nutritional support. METHODS:
      Arteriovenous neoadjuvant FLEOX chemotherapy was administered to 50 patients of
      gastric cancer with advanced abdominal lymph node metastases. Of the 50 patients,
      42 had never received any previous therapy and preoperative CT scanning revealed
      unresectable tumors because of advanced lymph node (station No.3, 7, 9, 12) or
      distant lymph node (No.14,16) metastases. The other 8 were characterized with
      relapse of severe lymph node metastases or with unresectable lymph node
      metastases demonstrated by exploratory laparotomy. Arteriovenous neoadjuvant
      FLEOX chemotherapy was conducted as follows: from day 1 to day 5, 5-FU 370
      mg/m(2) and leukovorin 30 mg/kg intravenously, at day 6 and day 20, CDDP 70
      mg/m(2) and epotoside 70 mg/m(2) intraarterially. This FLEOX regimen was repeated
      every five weeks for two or three courses. Out of the 50 patients,12
      malnutritional cases received parenteral and/or enteral nutritional support
      according to the nutritional condition. Arteriovenous neoadjuvant FLEOX
      chemotherapy was then administered after the improvement of nutritional state.
      Their nutritional support methods were adapted to their chemotherapy as well.
      RESULTS: All the patients' general conditions and symptoms were improved
      significantly. For the 50 cases, the imageological and histological response rate
      (CR+PR) was 84.0%, and curative resection rate was 78.0%. Thus, 39 patients
      underwent subtotal or total gastrectomy, even combined organ resection, with
      D(2)+alpha or D(3) lymphadenectomy. Despite neoadjuvant chemotherapy, all
      malnutritional cases had significant weight gain after nutritional support, and
      other nutritional indexes,such as serum albumin, also resumed to normal.
      CONCLUSION: Arteriovenous neoadjuvant FLEOX chemotherapy proves favorable
      therapeutic effect for gastric cancer with advanced abdominal lymph node
      metastases, and downstages inoperable metastatic lymph nodes for radical
      operation. This combined modality regimen and nutritional support may play an
      important role in the treatment of advanced gastric cancer.

PMID- 18803043
TI  - [Prognosis analysis of surgical treatment for cancer of stomach fundus and cardia
      with invasion to body and tail of the pancreas].
AB  - OBJECTIVE: To investigate the prognostic factors of surgical treatment for the
      cancer of stomach fundus and cardia with invasion to body and tail of the
      pancreas. METHODS: A total of 135 patients with cancer of stomach fundus and
      cardia invading body and tail of the pancreas undergone surgical treatment were
      enrolled in this study. Twenty of them underwent laparotomy, while 115 underwent
      gastrectomy with pancreaticosplenectomy, even combined with the resection of
      other organs for macroscopic invasion to adjacent organs during surgery. The 3-,5
      year survival rates, morbidity of postoperative complications and mortality were
      followed up. The prognostic factors were evaluated by univariate and multivariate
      analyses. RESULTS: The median survival time of the patients undergone laparotomy
      was 4.7 months, of patients treated by gastrectomy combined with
      pancreaticosplenectomy was 30.5 months,and the difference was significant
      (chi(2)=403.8, P<0.01). The cumulative 3- and 5-year survival rates of the
      patients treated by gastrectomy combined with pancreaticosplenectomy were 48.3%
      and 26.6% respectively. Univariate analysis revealed that significant differences
      in prognosis of 115 patients undergone combined resection were demonstrated for
      the following factors: maximal dimension of tumor, macroscopic type, extent of
      lymph node metastasis according to the Japanese classification, No.10 or No.11
      lymph node metastasis,curability and number of invaded organs.And histological
      depth of invasion, extent of lymph node metastasis according to the Japanese
      classification, number of invaded organs and curability were significant
      prognostic factors, examined as variables by multivariate analysis (Cox's
      proportional hazard model, forward stepwise selection LR method). The
      postoperative complication rate and mortality of 135 patients were 20.0% and 3.5%
      respectively. CONCLUSIONS: For cancer located in stomach fundus and cardia with
      limited invasion to distal pancreas, gastrectomy combined with
      pancreaticosplenectomy should be performed to improve long-term outcomes. Best
      long-term survival outcomes would be attained if there are no lymph node
      metastases, or no incurable factors, or no other organ invasions.

PMID- 18803044
TI  - [Role of duodenum in regulation of plasma ghrelin level and body mass index after
      subtotal gastrectomy].
AB  - OBJECTIVE: To investigate the role of duodenum in regulation of ghrelin and body
      mass index (BMI) and the correlation between ghrelin and BMI after subtotal
      gastrectomy. METHODS: Forty-two patients with T(0-1)N(0-1)M(0) gastric cancer
      were divided into two groups after gastrectomy according to digestive
      reconstruction pattern, Billroth I group (n=23) and Billroth II group (n=19)
      respectively. Plasma ghrelin levels were determined by radioimmunoassay (RIA)
      before and at day 1, 7, 30 and 360 after gastrectomy,and BMIs were also measured.
      RESULTS: Two groups had identical postoperative trends in ghrelin alterations
      during the early stage, both dropping to nadir at day 1 (36.7% vs 35.7%), then
      markedly increasing at day 7 (51.0% vs 51.1%). At day 30, ghrelin level of
      Billroth I group was slightly higher than that of Billroth II group. At day 360,
      ghrelin level of Billroth I group recovered to 93.6%, approaching though lower
      than preoperative level and no significant difference was displayed, while
      ghrelin level of Billroth II group recovered only to 81.6% of preoperational
      level and significant difference existed (P=0.033). Compared with preoperative
      levels, ghrelin of two groups decreased by 6.9% and 18.4% while BMI by 3.3% and
      6.4% respectively, liner regression correlations were revealed in both groups
      between decrease magnitudes(R(1)(2)=0.297,P=0.00;R(2)(2)=0.559,P<0.001).
      CONCLUSIONS: Anatomico-physiological duodenum compensatively promotes ghrelin
      recovery, accordingly enhances BMI after gastrectomy. Regarding patients with
      insufficient ghrelin secretion, ghrelin is positively correlated with BMI.

PMID- 18803045
TI  - [Preoperative evaluation of the 64-slice spiral CT three dimensional angiography
      for vascular invasion in gastric cancer].
AB  - OBJECTIVE: To evaluate the preoperative diagnosis value of 64-slice spiral CT
      three dimensional angiography (3D CTA) for the vascular invasion in gastric
      cancer. METHODS: CT images of 40 patients diagnosed as gastric cancer by
      endoscope,who proceeded to surgical exploration from August 2006 to December
      2007,were collected. These images were rebuilt by 3D CTA to judge vascular
      invasion by gastric cancer in comparison with the surgical finding as standard
      reference. RESULTS: Successful 3D CTA reconstructions were performed for all
      these 40 patient images. Out of 40 cases, 14 cases presented vascular invasion in
      the 3D CTA, and 12 of 14 cases were proved to have vascular invasion in the
      surgery. For assessing vascular invasion with CTA, the sensitivity was 98.1% and
      the specificity was 96.4% respectively (Chi Square chi(2)=0.0099,P>0.05). There
      was no significant differences regarding vascular invasion in gastric cancer
      between preoperative 3D CTA assessment and surgical finding. CONCLUSION: Sixty
      four-slice spiral CT 3D angiography is effective in assessing vascular invasion
      in gastric cancer and is also valuable in clinical application.

PMID- 18803046
TI  - [Effects of intensive insulin therapy on insulin resistance and serum proteins
      after radical gastrectomy].
AB  - OBJECTIVE: To investigate the effects of intensive insulin therapy on insulin
      resistance(IR) and serum proteins after radical gastrectomy. METHODS: Twenty-two
      gastric cancer patients were randomly divided into the control (n=11) and
      intensive insulin therapy group (n=11), and underwent distal radical subtotal
      gastrectomy under epidural anesthesia. Fasting blood glucose (FBG), fasting
      insulin (FINS) and serum proteins were assayed preoperatively and at day 1, 3, 7
      postoperatively. Insulin resistance index was calculated using homeostasis model
      assessment (HOMA). The length of hospital stay and postoperative complications
      were recorded respectively. RESULTS: (1)The levels of FBG, FINS, lnHOMA-IR
      (P<0.01,P<0.05) and the incidence of insulin resistance were remarkably decreased
      by intensive insulin therapy after the surgical procedure.(2)The levels of serum
      transferrin (TRF), prealbumin (PRE) and retinal binding protein (RBP) in the
      intensive insulin therapy group were significantly improved as compared to
      control group after operation(P<0.05). (3) The duration of fever, antibiotic use,
      passage of gas by anus, length of hospital stay and the occurrence of
      postoperative complications were also significantly lower than those in control
      group(P<0.01,P<0.05). CONCLUSION: Compared to routine therapy, the intensive
      insulin therapy has more beneficial effects on the patients undergone distal
      radical subtotal gastrectomy in decreasing the insulin resistance, improving the
      status of nutrition and preventing postoperative complications.

PMID- 18803047
TI  - [Efficacy of early continuous hyperthermic peritoneal perfusion on patients with
      advanced gastric carcinoma after surgical resection].
AB  - OBJECTIVE: To evaluate the efficacy of early continuous hyperthermic peritoneal
      perfusion (CHPP) on patients of advanced gastric carcinoma after surgical
      resection. METHODS: Seventy patients were divided into control and treatment
      group. Patients in treatment group received CHPP 1 or 2 days postoperatively.
      Treatment was administered daily consecutively for 4 days. Patients in control
      group underwent resection of gastric carcinoma without CHPP. Chemotherapy was
      administered of Calcium Folinate and 5-Fluorouracil (LF regimen) intravenously
      for 6 cycles in both groups two or three weeks postoperatively. Survival and
      recurrence in both groups were observed and compared. RESULTS: One-year survival
      and recurrence rates were 83.3% and 8.3% in treatment group, 79.4% and 11.7% in
      control group, there were no significant differences between the two groups.
      Three-year survival and recurrence rates were 63.9% and 19.4 in treatment group,
      39.8% and 44.1% in control group, there were significant differences between the
      two groups. CONCLUSION: Early administration of CHPP to patients with advanced
      gastric carcinoma after surgery may be advantageous for preventing peritoneal
      metastasis and recurrence, thus may prolong survival time.

PMID- 18803048
TI  - [Evaluation of transhiatus esophagectomy for patients with esophageal cancer].
AB  - OBJECTIVE: To evaluate the transhiatus esophagectomy for patients with esophageal
      cancer. METHODS: Clinicopathological data of 46 patients with esophageal cancer
      undergone transhiatus esophagectomy by single surgeon team from May 2000 to July
      2007 were analyzed retrospectively. RESULTS: These 46 patients included 44
      esophageal squamous cell carcinomas,1 esophageal adenocarcinoma and 1 esophageal
      carcinoid. The lesions of 11 patients located at neck segment, 21 at upper
      segment, 5 at middle segment, and 9 at lower segment. All the patients were
      classified according to UICC TNM stage classification: 3 cases as stage 0, 6
      cases as stage I, 17 cases as stage II a, 2 cases as stage II b, 16 cases as
      stage III. Six patients received preoperative chemotherapy and pathological
      complete response was seen in 2 cases. Reconstruction with stomach was performed
      in 42 cases and with colon interposition in 4 cases.All the tumors were resected,
      and there was no perioperative death. All the resected margins were
      pathologically clear. Postoperative complications occurred in 12 cases and were
      successfully treated, including 2 cases of hoarseness, 3 cases of cardiac
      arrhythmia,1 case of bilateral pleural effusion, and 6 cases of small anastomotic
      leakage at neck. CONCLUSION: Transhiatus esophagectomy is an ideal choice in
      surgical treatment for patients with esophageal cancer, especially for the ones
      of aged, poor cardiac or pulmonary function, who can not afford the thoracotomy.

PMID- 18803049
TI  - [Effects of different CO2 pressure pneumoperitoneum on the migration and
      cytoskeleton in gastric cancer cells].
AB  - OBJECTIVE: To investigate the influence of CO(2) and He insufflation administered
      at different pressures on the migration and cytoskeleton of cultured human
      gastric cancer cells. METHODS: The cultured gastric cancer cells MKN-45 were
      exposed to a CO(2) or He environment maintained at different pressures (12, 15 mm
      Hg). After 0, 2, 4, 6, 8 hours exposure to CO(2) or He environment, pH of the MKN
      45 cells culture media was measured with blood gas analysis. The cell migration
      was detected with Transwell technology. The cell cytoskeleton was observed with
      laser confocal microscope. RESULTS: The media pH was acid after exposure to CO(2)
      environment, while it was basic in the He group. The number of cells passing
      millipore in 12 mm Hg CO(2) or He insufflation pressure were not significantly
      different with control group (P>0.05), however in 15 mm Hg pressure CO(2) group,
      it was significantly decreased as compared to control group (P<0.01). The
      microfilament and microtubule in gastric cancer cell were ambiguous in 15 mm Hg
      pressure CO(2) group. CONCLUSIONS: There are no obvious effects on the migration
      and cytoskeleton of MKN-45 cells under 12 mm Hg CO(2) insufflation pressure. The
      migration and cytoskeleton of MKN-45 cells can be inhibited in 15 mm Hg CO(2)
      pneumoperitoneum environment.

PMID- 18803050
TI  - [Association between hypermethylation of Syk gene and clinicopathological
      characteristics in colorectal cancer patients].
AB  - OBJECTIVE: To investigate the association of the methylation status and
      expression level of Syk gene with the clinicopathological characteristics in
      colorectal cancer (CRC) patients. METHODS: Methylation-specific PCR(MSP) and RT
      PCR techniques were used to analyze the methylation status and expression level
      of Syk gene in cancer and normal tissues of 120 CRC patients, meanwhile,
      association of the methylation status and expression level of Syk gene with the
      clinicopathological characteristics and the prognosis were studied. RESULTS: (1)
      Syk gene expression was not found in 48 cancer tissues out of 120 patients and
      was found in all the normal tissues.The difference was significant. (2) Loss of
      Syk expression was found in 37 patients with Syk hypermethylation, and in 11 out
      of 83 patients with Syk nonmethylation. (3) The methylation status of Syk gene
      was correlated with the lymph node status and the Dukes stage, but not with other
      clinicopathological parameters. (4) The follow-up data revealed that the 3-year
      survival of patients with Syk hypermethylation was lower than that of patients
      without Syk hypermethylation(73.5% vs.95.7%,P=0.007),and postoperative recurrence
      rate significantly increased in the Syk hypermethylation group (32.4% vs.
      8.4%,P=0.02). CONCLUSION: Hypermethylation leads to silence of Syk gene involved
      in the initiation of colorectal cancer, which increases the infiltration of
      colorectal cancer cells, postoperative relapse and decreases the postoperative 3
      year survival time.

PMID- 18803051
TI  - [Comparison of the sensibility and specificity between single-stranded
      conformation polymorphism and denaturing high-performance liquid chromatography
      in screening hMSH2 and hMLH1 gene mutations in hereditary non-polyposis
      colorectal cancer].
AB  - OBJECTIVE: To compare the sensibility and specificity between single-stranded
      conformation polymorphism (SSCP) and denaturing high-performance liquid
      chromatography (DHPLC) in screening hMSH2 and hMLH1 gene mutations for the
      diagnosis of hereditary non-polyposis colorectal cancer (HNPCC). METHODS: Seven
      Chinese HNPCC kindreds were collected. PCR-SSCP and DHPLC were used to screen the
      coding regions of hMSH2 and hMLH1 genes and the abnormal profiles were sequenced
      by a 377 DNA sequencer. RESULTS: Seven gene sequence variations of hMSH2 or hMLH1
      were found. Among them, 4 variations were not found by SSCP, but by DHPLC. The
      sensibility of SSCP and DHPLC were 51.6% and 100% respectively, and the
      specificity were 66.6% and 93.3% respectively. CONCLUSION: DHPLC has better
      sensibility and specificity in screening hMSH2 and hMLH1 gene mutation as
      compared to SSCP. DHPLC is an ideal method in the diagnosis of HNPCC.

PMID- 18803052
TI  - [Expression of minichromosome maintenance protein 2 in colonic adenocarcinoma,
      adenoma and normal colonic mucosa and its clinical significance].
AB  - OBJECTIVE: To investigate the expression differences of minichromosome
      maintenance 2 (MCM2) mRNA and protein among colon adenocarcinoma, colon adenoma
      and normal mucosa, and among different clinicopathological types of adenomas.
      METHODS: Fifty specimens, including 33 colonic adenomas, 12 colonic
      adenocarcinomas and 5 normal colonic mucosa were selected. Each specimen was
      divided into two parts, one for immunohistochemistry and the other for real-time
      RT-PCR. Expression differences of MCM2 mRNA among the colonic adenocarcinoma,
      adenoma and normal colonic mucosa were evaluated by REST-XL software. RESULTS:
      The expression of MCM2 was observed in the basal third to half of the colonic
      crypts in normal mucosa, while throughout the epithelium in the colonic
      adenocarcinomas and adenomas. However, the expression of MCM2 mRNA in the
      adenocarcinomas was significantly higher than that in the adenomas(P=0.001). The
      MCM2 mRNA expression was elevated in the adenoma with villous type, in the
      conditions of high-grade dysplasia, larger size, sessile morphology and in
      patients of older ages, but the difference was not significant by REST-XL
      (P>0.05). CONCLUSION: The difference of MCM2 expression between the adenoma and
      the adenocarcinoma indicates its potential value in the early diagnosis of
      colonic cancer.

PMID- 18803053
TI  - [Effect of mesenteric lymphatic duct ligation on the system inflammation during
      the intestinal ischemia-reperfusion].
AB  - OBJECTIVE: To estimate the effect of the lymph duct ligation on systemic
      inflammatory factors and endotoxins during intestinal ischemia-reperfusion (I/R).
      METHODS: Male SD rats underwent occlusion of superior mesenteric artery for 60
      min followed by reperfusion for 120 min plus lymph duct ligation or not. Forty
      rats were randomly divided into 4 groups: group A (blank); group B (sham); group
      C (intestinal I/R); group D (intestinal I/R plus lymph duct ligation). Mesenteric
      lymph nodes were harvested for standard bacteriologic cultures. The endotoxin, D
      lactate, diamine oxidase (DAO), and cytokines in serum were detected. RESULTS:
      The rates of bacterial translocation to mesenteric lymph nodes were 40% in group
      C and 20% in group D. No positive lymph node cultures were encountered in any of
      group A and B. The serum cytokines (except for sICAM-1) , D-lactate, DAO and
      endotoxin levels were lower in group D than those in group C (P<0.05), but both
      were higher than those in group A and B (P<0.05). CONCLUSION: During intestinal
      I/R injury, blockage the lymph flow from gut into bloodstream decreases the
      levels of cytokines, and significantly attenuates the increase in intestinal
      permeability.

PMID- 18803054
TI  - [Empirical study in the relation of gastric mucosal lesion with gastric emptying
      and gastric acid secretion].
AB  - OBJECTIVE: To study the precise cause and the specific procedure about gastric
      mucosal lesion in rats with water immersion-restraint stress(WRS). METHODS: One
      hundred and forty-four Wistar rats were divided into 9 groups randomly: A, B, C,
      D, E, F, G, H and I group. There were 16 rats in each group. A, B and C groups
      underwent gastric emptying determination. Emptying rate of gastric fluid was
      determined with radiate nuclide (99m)Tc. D, E and F groups underwent gastric acid
      secretion determination after cleaning gastric contents and pylorus ligation. G,
      H and I groups underwent gastric acid secretion determination after pylorus
      ligation without cleaning gastric contents. Gastric mucosal lesion ulcer
      index(UI) was evaluated. The relationship between of gastric mucosal lesion and
      gastric emptying rate and gastric acid secretion were examined. RESULTS: Gastric
      emptying rate decreased obviously when the WRS time was prolonged. There were
      significant differences among B (WRS 2 h), C group (WRS 4 h) and A group
      (controlled group) (P<0.01). There was also significant difference between B and
      C group (P<0.01).The rats' gastric acid secretion was inhibited significantly.
      The differences among E (WRS 2 h), F (WRS 4 h) and D groups (controlled group)
      were significant (P<0.01). There was no significant difference between F and E
      groups (P>0.05). The gastric mucosal lesions were aggravated with time of stress.
      Gastric contents cleaning could effectively prevent gastric mucosal lesions
      originated by stress .The operation had no influence on this test. There were
      significant gastric mucosal lesion UI in B and C groups compared with A group
      (P<0.01). The difference between B and C group was significant (P<0.01).There
      were no gastric mucosal lesions in A, D, E, F and G groups. However, There was
      significant difference between I and F group (P<0.01). No significant difference
      were found among A, D, E, F and G groups (P>0.05). There were significant
      difference between H and B group and also between I and C group (P<0.01).
      CONCLUSIONS: WRS can induce gastric emptying disturbance, reduce gastric acid
      secretion and cause gastric mucosal lesion. As a factor inducing gastric mucosal
      lesion, acid can damage gastric mucosa as long as it exists without necessary
      peracid. The prolongation of acid with gastric mucosa contact period and the
      decrease of gastric mucosa resistance are perhaps the major causes of gastric
      mucosal lesion. Besides anti-acid, giving facilitative gastric emptying drugs and
      gastric lavage during stress ulcer prevention and cure should be considered. Acid
      evacuation in time is also a major cure for gastritis and recurrent ulcer.

PMID- 18803055
TI  - [Effects of phosphatase of regenerating liver cell-3 gene silence by RNA
      interference on the expression of matrix metalloproteinases-2,-9 in human colon
      cancer cells].
AB  - OBJECTIVE: To explore the effects and associated mechanism of phosphatase of
      regenerating liver cell-3 (PRL-3) on the invasion of human colon cancer cell.
      METHODS: After colon cancer cell line HCT116 was transfected with PRL-3 small
      interfering RNA (siRNA), the mRNA and protein expression of PRL-3 and matrix
      metalloproteinase 2 (MMP-2) and MMP-9 were determined by real time RT-PCR and
      Western blot respectively. The anchorage-independent growth was examined using
      clone formation assay in soft agar, and invasion ability was evaluated by boyden
      chamber model. Then the transfected HCT116 cells were implanted into nude mice
      and the tumor growth was observed. RESULTS: PRL-3 siRNA could inhibit anchorage
      independent growth of HCT116 cells in a dose-dependent manner in vitro. The mRNA
      and protein expression of MMP-2 and MMP-9 were down-regulated by PRL-3 siRNA.
      HCT116 cells invaded striated muscle and vessels in control nude mice but such
      phenomena were not found in transfected HCT116-implanted nude mice in vivo.
      CONCLUSION: PRL-3 siRNA inhibit the invasion of colon cancer cells possibly
      through the down-regulation of MMP-2 and MMP-9.

PMID- 18803056
TI  - [Expression of chemokine receptor CXCR4 in colorectal carcinoma and its
      relationship with clinicopathological parameters].
AB  - OBJECTIVE: To investigate the expression of chemokine receptor CXCR4 in
      colorectal carcinoma and its relationship with the clinicopathological
      parameters, and to reveal the role of CXCL12/CXCR4 in the invasion and metastasis
      of colorectal carcinoma. METHODS: CXCR4 expression was studied in 53 colorectal
      cancer tissues and 27 normal tissues by immunohistochemistry. Its relationship
      with clinicopathological characteristics of colorectal cancer patients were
      analyzed. The CXCR4 expression in tumor and normal specimens and its metastatic
      sites were assessed by RT-PCR and Western blot. RESULTS: Fifty-three colorectal
      cancer patients,collected from July 2005 to February 2007 in our hospital,were
      enrolled in this study. CXCR4 was positive in 39 cancer tissue specimens(73.6%)
      and its high expression rate (in > 50% of cells) was 45.3%. High CXCR4 expression
      rate was significantly higher in patients with lymph node metastases (N(1)+N(2):
      65.4%) than that in those without metastases(N(0) 25.9%). There were also
      associations between the high CXCR4 expression and the vascular and lymphatic
      vessel invasions (P<0.01). Meanwhile, there was a rising trend of high expression
      rate according to American Joint Committee on Cancer (AJCC) stage and pathologic
      grade,but no significant difference was found(P>0.05). There were no significant
      correlation of CXCR4 expression with clinicopathological parameters such as tumor
      location, tumor size, depth of tumor invasion(P>0.05). In addition, the CXCR4
      mRNA expression in primary tumor specimens (n=27) from AJCC stage IIII( patients
      was significantly higher than that in normal tissues. CXCR4 mRNA expression of
      liver metastasis specimens(n=5) was significantly higher as compared with the
      primary colorectal cancer specimens(P<0.01). CONCLUSIONS: Chemokine receptor
      CXCR4 is associated with the progression of colorectal carcinoma. High CXCR4
      expression is associated with metastasis. The CXCL12-CXCR4 signaling pathway may
      be a potential novel target of therapy for patients with colorectal cancer.

PMID- 18803057
TI  - [Expression of phosphatase of regeneration liver-3 in human colorectal carcinoma
      and its prognosis value].
AB  - OBJECTIVE: To investigate the expression of phosphatase of regeneration liver
      3(PRL-3) protein and its relationship with tumor invasion and metastasis in human
      colorectal carcinoma,and elucidate prognostic value. METHODS:
      Immunohistochemistry method was applied to detect the PRL-3 expression in the
      primary tumor specimens and paired paratumor normal tissues from 46 colorectal
      carcinoma patients, the adenoma tissues from 6 patients with colorectal adenoma,
      all the metastatic lymph nodes from 29 cases and the metastatic liver lesions
      from 6 cases. The relationship between PRL-3 expression and clinicopathologic
      parameters was analyzed and a survival curve was achieved according to Kaplan
      Meier method. RESULTS: No or weak PRL-3 protein expression was detected in normal
      colorectal mucosa and colorectal adenoma. In colorectal carcinoma tissues, PRL-3
      expression was confirmed in 26 of 46 cases (56.5%) of primary colorectal
      carcinomas (with lymph node metastasis 63.0%, without lymph node metastasis
      37.0%, P=0.001), 26 of 29 (89.7%) lymph node metastases, and 5 of 6 liver
      metastases. The expression of PRL-3 was assembled in the cytoplasm of carcinoma
      cells and more intensively on the cell membrane.Analysis of the relationship
      between PRL-3 expression and the clinicopathologic features showed that PRL-3
      expression was closely associated with tumor stage (P=0.019), lymph node
      metastasis (P=0.026), but no relationship with age, sex, tumor size, degree of
      differentiation was founded (P<0.05). The mean follow-up time was 41.4 months and
      results showed that patients with positive expression of PRL-3 had a
      significantly poorer prognosis than those with negative PRL-3 expression
      group(P=0.032). CONCLUSIONS: PRL-3 protein plays a novel role in tumor
      progression and metastasis of colorectal carcinoma. PRL-3 can be expected to be a
      potential predictive biomarker for identifying the prognosis in colorectal
      carcinoma patients.

PMID- 18803058
TI  - Validation of Varian's AAA algorithm with focus on lung treatments.
AB  - INTRODUCTION: The objective of this study was to examine the accuracy of the
      Anisotropic Analytical Algorithm (AAA). A variety of different field
      configurations in homogeneous and in inhomogeneous media (lung geometry) was
      tested for the AAA algorithm. It was also tested against the present Pencil Beam
      Convolution (PBC) algorithm. MATERIALS AND METHODS: Two dimensional (2D) dose
      distributions were measured for a variety of different field configurations in
      solid water with a 2D array of ion chambers. The dose distributions of patient
      specific treatment plans in selected transversal slices were measured in a Thorax
      lung phantom with Gafchromic dosimetry films. A Farmer ion chamber was used to
      check point doses in the Thorax phantom. The 2D dose distributions were evaluated
      with a gamma criterion of 3% in dose and 3 mm distance to agreement (DTA) for the
      2D array measurements and for the film measurements. RESULTS: For AAA, all fields
      tested in homogeneous media fulfilled the criterion, except asymmetric fields
      with wedges and intensity modulated plans where deviations of 5 and 4%,
      respectively, were seen. Overall, the measured and calculated 2D dose
      distributions for AAA in the Thorax phantom showed good agreement -- both for 6
      and 15 MV photons. More than 80% of the points in the high dose regions met the
      gamma criterion, though it failed at low doses and at gradients. For the PBC
      algorithm only 30-70% of the points met the gamma criterion. CONCLUSION: The AAA
      algorithm has been shown to be superior to the PBC algorithm in heterogeneous
      media, especially for 15 MV. For most treatment plans the deviations in the lung
      and the mediastinum regions are below 3%. However, the algorithm may
      underestimate the dose to the spinal cord by up to 7%.

PMID- 18803059
TI  - Nanomechanical strength mechanisms of hierarchical biological materials and
      tissues.
AB  - Biological protein materials (BPMs), intriguing hierarchical structures formed by
      assembly of chemical building blocks, are crucial for critical functions of life.
      The structural details of BPMs are fascinating: They represent a combination of
      universally found motifs such as alpha-helices or beta-sheets with highly adapted
      protein structures such as cytoskeletal networks or spider silk nanocomposites.
      BPMs combine properties like strength and robustness, self-healing ability,
      adaptability, changeability, evolvability and others into multi-functional
      materials at a level unmatched in synthetic materials. The ability to achieve
      these properties depends critically on the particular traits of these materials,
      first and foremost their hierarchical architecture and seamless integration of
      material and structure, from nano to macro. Here, we provide a brief review of
      this field and outline new research directions, along with a review of recent
      research results in the development of structure-property relationships of
      biological protein materials exemplified in a study of vimentin intermediate
      filaments.

PMID- 18803060
TI  - Internalization, cytotoxicity, apoptosis, and tumor necrosis factor-alpha
      expression in rat alveolar macrophages exposed to various dusts occurring in the
      ceramics industry.
AB  - In 1997 The International Agency for Research on Cancer classified some exposures
      to crystalline silica as carcinogenic to humans. Such exposures were acknowledged
      to be very variable, and even in the same monograph it was admitted that coal
      dust, containing as much as 20% quartz, could not be classified. Clearly there is
      a need to develop methods for assessing any risks posed by various silica
      containing dusts in different workplaces. A European collective research project,
      SILICERAM, was launched with the aim of assessing the toxicity of various dusts
      in the ceramics industry and improving worker protection. This study examined the
      effect of particles, namely, DQ12 quartz, China clay, feldspar, and a sample
      resembling a typical mixture used in the ceramic industry (a "contrived sample"
      or CS), on NR8383, a rat alveolar macrophage (AM) cell line. Titanium dioxide and
      aluminum oxide were also used as negative controls. Confocal microscopy
      observations showed internalization of DQ12 and CS in NR8383. Cell viability
      decreased dramatically after a 2-h incubation exposure period with DQ12 (-71%).
      CS was less toxic than DQ12 at 2 h. China clay and feldspar were slightly
      cytotoxic to NR8383 cells. DQ12 induced apoptosis, with a smaller effect of CS
      and China clay. TNFalpha gene expression was analyzed by RT-PCR. DQ12, at a
      noncytotoxic dose of 10 microg/cm(2), induced a significant expression of
      TNFalpha (+2 times increase). In contrast, similar doses of CS and China clay did
      not produce a significant increase, while TiO2 and Al2O3 displayed no effect. Co
      treatment with 10 microM aluminum lactate significantly reduced the effects of
      silica-containing particles on cytotoxicity, apoptosis, and TNFalpha expression.

PMID- 18803062
TI  - Comments on Dodson et al., A technical comparison of evaluating asbestos
      concentration by phase contrast microscopy (PCM), scanning electron microscopy
      (SEM), and analytical transmission electron microscopy (ATEM) as illustrated from
      data generated from a case report.

PMID- 18803064
TI  - Influence of body position when considering the ecological validity of laboratory
      time-trial cycling performance.
AB  - The aims of this study were to compare the physiological demands of laboratory-
      and road-based time-trial cycling and to examine the importance of body position
      during laboratory cycling. Nine male competitive but non-elite cyclists completed
      two 40.23-km time-trials on an air-braked ergometer (Kingcycle) in the laboratory
      and one 40.23-km time-trial (RD) on a local road course. One laboratory time
      trial was conducted in an aerodynamic position (AP), while the second was
      conducted in an upright position (UP). Mean performance speed was significantly
      higher during laboratory trials (UP and AP) compared with the RD trial (P <
      0.001). Although there was no difference in power output between the RD and UP
      trials (P > 0.05), power output was significantly lower during the AP trial than
      during both the RD (P = 0.013) and UP trials (P = 0.003). Similar correlations
      were found between AP power output and RD power output (r = 0.85, P = 0.003) and
      between UP power output and RD power output (r = 0.87, P = 0.003). Despite a
      significantly lower power output in the laboratory AP condition, these results
      suggest that body position does not affect the ecological validity of laboratory
      based time-trial cycling.

PMID- 18803063
TI  - Effects of metals within ambient air particulate matter (PM) on human health.
AB  - We review literature providing insights on health-related effects caused by
      inhalation of ambient air particulate matter (PM) containing metals, emphasizing
      effects associated with in vivo exposures at or near contemporary atmospheric
      concentrations. Inhalation of much higher concentrations, and high-level
      exposures via intratracheal (IT) instillation that inform mechanistic processes,
      are also reviewed. The most informative studies of effects at realistic exposure
      levels, in terms of identifying influential individual PM components or source
      related mixtures, have been based on (1) human and laboratory animal exposures to
      concentrated ambient particles (CAPs), and (2) human population studies for which
      both health-related effects were observed and PM composition data were available
      for multipollutant regression analyses or source apportionment. Such studies have
      implicated residual oil fly ash (ROFA) as the most toxic source-related mixture,
      and Ni and V, which are characteristic tracers of ROFA, as particularly
      influential components in terms of acute cardiac function changes and excess
      short-term mortality. There is evidence that other metals within ambient air PM,
      such as Pb and Zn, also affect human health. Most evidence now available is based
      on the use of ambient air PM components concentration data, rather than actual
      exposures, to determine significant associations and/or effects coefficients.
      Therefore, considerable uncertainties about causality are associated with
      exposure misclassification and measurement errors. As more PM speciation data and
      more refined modeling techniques become available, and as more CAPs studies
      involving PM component analyses are performed, the roles of specific metals and
      other components within PM will become clearer.

PMID- 18803065
TI  - Typologies of Greek inactive older adults based on reasons for abstaining from
      exercise and conditions for change.
AB  - The main purpose of this study was to examine typologies of non-exercisers based
      on reasons for physical inactivity and conditions reported to be necessary to
      change exercise behaviour. These typologies were then compared on psychological
      variables of interest and exercise history. Questionnaires were distributed to
      Greek older adults aged 60 and above who were recruited from social clubs and
      city cafes. Only individuals engaging in no regular exercise were recruited (n =
      188). The results of hierarchical and k-means cluster analyses revealed two
      clusters for males ("approachable" and "unconvinced") and three for females
      ("unconcerned", "approachable", and "unconvinced"). The clusters differed
      significantly on psychological variables not used in the cluster solution.
      Exercise history distinguished between clusters only among males. The results
      reveal that physically inactive older adults are not a homogeneous group of
      individuals. Implementers of physical activity interventions should probably use
      a range of strategies that take into consideration that some sedentary older
      adults are more amenable to consider taking up exercise than others.

PMID- 18803066
TI  - On passion and sports fans: a look at football.
AB  - The purpose of the present research was to test the applicability of the
      Dualistic Model of Passion (Vallerand et al., 2003) to being a sport (football)
      fan. Three studies provided support for this dualistic conceptualization of
      passion. Study 1 showed that harmonious passion was positively associated with
      adaptive behaviours (e.g. celebrate the team's victory), whereas obsessive
      passion was positively associated with maladaptive behaviours (e.g. risking
      losing one's job to go to a game). Study 2 used a short Passion Scale and showed
      that harmonious passion was positively related to the positive affective life of
      fans during the 2006 FIFA World Cup, psychological health (self-esteem and life
      satisfaction), and public displays of adaptive behaviours (e.g. celebrate the
      team's victory into the streets), whereas obsessive passion was predictive of
      maladaptive affective life (e.g. hating opposing teams' fans) and behaviours
      (e.g. mocking opposing teams' fans). Finally, Study 3 examined the role of
      obsessive passion as a predictor of partner's conflict that in turn undermined
      partner's relationship satisfaction. Overall, the present results provided
      support for the Dualistic Model of Passion. The conceptual and applied
      implications of the findings are discussed.

PMID- 18803067
TI  - Health benefits of Kung Fu: a systematic review.
AB  - The Chinese martial arts (Kung Fu) have existed for centuries and are generally
      accepted as being beneficial for health without much empirical data. The aim of
      this systematic review was to assess the health effects of "hard" Kung Fu styles
      by performing electronic and manual searches of the literature. The aspects of
      health and the Kung Fu style examined varied between most studies; in some cases,
      the martial art group consisted of practitioners of other martial art styles
      also. Of 2103 references identified, only nine papers were eligible and reviewed.
      All were observational studies, observing a range of health aspects possibly
      related to Kung Fu training or performance. Our findings suggest that there is no
      evidence that Kung Fu practice is associated with the prevention or treatment of
      any health condition. However, as a moderate- to high-intensity form of aerobic
      exercise, it may confer benefits similar to those attributed to other aerobic
      training modalities. However, this hypothesis remains to be tested in clinical
      trials. Physiological benefits (e.g., aerobic capacity and bone density) may be
      associated with long-term Kung Fu practice. Future research in this area should
      adopt experimental designs, clearly identifying eligibility criteria, testing and
      training protocols, and include health-related outcomes and documentation of
      adverse events, to advance knowledge in this field.

PMID- 18803068
TI  - Diagnostic interaction: the patient as a source of knowledge?
AB  - OBJECTIVE: To explore diagnostic interaction to understand more about why some
      problems appear medically unexplained. DESIGN: A qualitative discourse analysis
      case study. SETTING: Encounters between women patients and general practitioners
      in primary healthcare. SUBJECTS: Microanalysis of two audiotaped consultations
      without a clear-cut diagnosis and opposing levels of mutuality between doctor and
      patient. MAIN OUTCOME MEASURES: Descriptions of linguistic patterns in diagnostic
      interaction. RESULTS: Two patterns were identified demonstrating how different
      ways of speech acts contribute or obstruct diagnostic interaction and common
      ground for understanding. To invite or reject the patient into/from the
      diagnostic process, and to recognize or stereotype the patient may impose on how
      illness stories are perceived as medically unexplained. CONCLUSION: Making sense
      of illness can be enhanced by inviting and recognizing the patient's story.

PMID- 18803070
TI  - Ziprasidone versus olanzapine, risperidone or quetiapine in patients with chronic
      schizophrenia: a 12-week open-label, multicentre clinical trial.
AB  - The efficacy, safety and tolerability of ziprasidone versus the comparators
      olanzapine, risperidone or quetiapine were investigated in adult patients with
      chronic schizophrenia, schizoaffective and schizophreniform disorders, with lack
      of efficacy or intolerance to their previous antipsychotic treatment based on
      clinical judgement of the investigator. A total of 293 patients were randomized
      to 12 weeks treatment with either ziprasidone 80-160 mg/day (n=147) or with one
      of the comparator drugs (n=146). In the latter group the investigator could
      choose between olanzapine 10-20 mg/day (n=24), risperidone 4-8 mg/day (n=22) or
      quetiapine 300-750 mg/day (n=97). The study comprised four visits including a
      baseline examination prior to randomization and further examinations at the end
      of weeks 1, 4 and 12. Ziprasidone was non-inferior (defined as a difference of 7
      units or less on the PANSS scale to the disadvantage of ziprasidone) to the
      composite group (olanzapine, risperidone or quetiapine) on the total PANSS score
      as well as on all subscores (P<0.0001); there were no significant between-group
      differences in the CGI-S and I and UKU scores. Ziprasidone-treated patients lost
      an average of 2.1 kg in the 12 weeks of the study, the mean weight for
      risperidone and quetiapine remained unchanged, and patients receiving olanzapine
      gained 3.1 kg on average.

PMID- 18803071
TI  - A novel 1,25-dihydroxyvitamin D-activin A pathway in human alveolar macrophages
      is dysfunctional in patients with pulmonary alveolar proteinosis (PAP).
AB  - We have shown that activin A, a cytokine implicated in regulating B-cell
      proliferation, is severely deficient in alveolar macrophages from patients with
      pulmonary alveolar proteinosis (PAP), an autoimmune disorder characterized by
      surfactant accumulation and neutralizing autoantibodies to granulocyte-macrophage
      colony stimulating factor. Mechanisms of activin regulation in alveolar
      macrophages are not well understood. Based on previous gene array results from
      PAP bronchoalveolar lavage cells suggesting deficiencies in vitamin D target
      genes, and on recent evidence of vitamin D receptor elements (VDREs) in the human
      activin A gene promoter, we investigated the effects of 1,25-dihydroxyvitamin D
      (vitamin D(3)) on activin A expression in alveolar macrophages from healthy
      individuals and PAP patients. Activin A expression was stimulated by LPS in
      cultures of either healthy control or PAP alveolar macrophages; in contrast,
      vitamin D(3) increased activin A only in healthy controls but not in PAP.
      Compared to healthy controls, freshly obtained (uncultured) PAP alveolar
      macrophages displayed healthy intrinsic vitamin D receptor expression but
      deficient expression of vitamin D target genes, cathelicidin and thioredoxin
      interacting protein. PAP patients also demonstrated a relative insufficiency of
      circulating vitamin D. Investigation of activin A in murine alveolar macrophages
      confirmed a lack of functional response to vitamin D as anticipated since murine
      activin A does not contain VDREs. Results suggest that mechanisms of activin A
      deficiency in PAP alveolar macrophages may involve dysregulation of a novel
      species-specific vitamin D-activin A pathway.

PMID- 18803072
TI  - Computer-based intervention with coaching: an example using the Incredible Years
      program.
AB  - Increases in personal computer ownership and Internet use patterns provide a
      potential avenue for dissemination of evidence-based prevention and treatment
      interventions. The authors describe the implementation of a psychoeducational
      intervention (the Incredible Years parenting program, which is designed to
      promote behavioral change in parents and children) using a hybrid model combining
      computer- and web-based delivery with professional intervention via phone calls,
      electronic messages, and home visits. The model attempted to simulate many of the
      parent training methods shown to be successful in the original program. The
      intervention was implemented with 90 Head Start families who reported elevated
      levels of child behavior problems. Of the 45 families offered the intervention in
      the final year of the project, 37 (82%) completed at least half the program and
      34 (76%) completed the entire intervention using procedures refined in light of
      the initial year's experience. These participants reported high achievement of
      their self-determined goals and were highly satisfied with the intervention. The
      combination of technology with professional coaching represents a potential model
      for adapting and disseminating evidence-based interventions.

PMID- 18803073
TI  - Save the heart - optimizing our methods.

PMID- 18803074
TI  - Clinical results of drug eluting stents compared to bare metal stents for
      patients with ST elevation acute myocardial infarction.
AB  - OBJECTIVE: To investigate the clinical outcomes in patients with ST segment
      elevation acute myocardial infarction (STEMI) treated with drug eluting stents
      (DES) versus a matched control group of patients with STEMI treated with bare
      metal stents (BMS). METHODS: This registry included 122 patients with STEMI
      undergoing primary coronary angioplasty with DES implantation at our institution.
      The control group consisted of 506 patients implanted with BMS, who were matched
      for age, infarct location, and diabetic status. The incidences of major adverse
      cardiac events (MACE) including target vessel/lesion revascularization (TVR/TLR)
      and stent thrombosis were assessed up to 12 months. RESULTS: Twelve months follow
      up showed a non-significant trend towards reduced deaths (3.3% versus 7.1%,
      P=0.1), significantly reduced recurrent MI (0.0% versus 6.1%, P=0.02), TVR (5.7%
      versus 15.2%, P=0.006) and TLR (2.5% versus 14.0%, P=0.004) events in the DES
      group as compared to BMS group. The composite incidences of MACE at 12 months
      follow-up was lower in the DES group (11.5%) as compared to the BMS group (21.3%,
      P=0.01). CONCLUSION: According to our experiences, the use of DES in STEMI is
      safe and effective as compared to BMS. DES was effective in reducing the
      incidence of restenosis outcomes and overall adverse cardiac events up to 12
      months.

PMID- 18803075
TI  - Fetal-shaped intracardiac masses.

PMID- 18803076
TI  - Evidence-based neurosurgery--is it possible?

PMID- 18803079
TI  - Radiotherapy as an adjuvant in the management of intracranial meningiomas: are we
      practising evidence-based medicine?
AB  - Although increasingly used, the precise role of radiotherapy in the management of
      meningiomas is still disputed. The objective of this study, therefore, was to
      appraise the evidence for adjuvant radiotherapy in benign and atypical
      intracranial meningiomas, and to compare and contrast it with the current opinion
      and practice of neurosurgeons in the United Kingdom and the Republic of Ireland.
      The use of radiotherapy as a primary treatment strategy or its use in the
      treatment of recurrence was not considered. We performed a systematic review of
      the evidence for adjuvant radiotherapy in benign and atypical intracranial
      meningiomas, surveyed current opinion amongst neurosurgeons involved in such
      cases and ascertained local practice using data from the regional cancer
      registry. Overall, 10 cohorts were identified that fulfilled our eligibility
      criteria. Four studies showed significantly improved local control in patients
      receiving adjuvant radiotherapy for incompletely resected grade I meningiomas.
      Our survey demonstrated that the vast majority (98%) of neurosurgeons would not
      recommend adjuvant radiotherapy in grade I meningioma. In grade II meningioma,
      most (80%) would not advocate adjuvant radiotherapy if completely excised, but
      the majority (59%) would recommend radiotherapy in cases of subtotal resection.
      Significant variation in opinion between centres exists, however, particularly in
      cases of completely resected atypical meningiomas (p = 0.02). Data from the
      Eastern Cancer Registration and Information Centre appears to be in line with
      these findings: less than 10% of patients with grade I meningiomas, but almost
      30% of patients with grade II meningiomas received adjuvant radiotherapy in the
      Eastern region. In conclusion, our study has highlighted significant variation in
      opinion and practice, reflecting a lack of class 1 evidence to support the use of
      adjuvant radiotherapy in the treatment of meningiomas. Efforts are underway to
      address this with a randomized multicentre trial comparing a policy of watchful
      waiting versus adjuvant irradiation.

PMID- 18803080
TI  - Giant vestibular schwannomas: focusing on the differences between the solid and
      the cystic variants.
AB  - In vestibular schwannomas (VS), the tumour size, as well as the size of the
      cystic component, have a considerable bearing on the outcome. This study
      addresses the differences between the cystic and solid variants of giant
      vestibular schwannomas. The study included 62 patients with giant VSs, of which
      40 were solid and 22 were cystic (those in which cystic component greater or
      equal to 30% of the total tumour volume). The cystic tumour group was further
      divided into type A (31-60% volume of the cyst within tumour), type B (61-90%
      intra-tumoural cyst volume) and type C (more than 90% volume of the cyst). The
      clinicoradiological features, operative findings, histopathological
      characteristics and outcome of surgery of the two groups were compared. The mean
      duration of symptoms for the solid and cystic tumours were 21.1 and 26.2 months,
      respectively. However, six patients with cystic tumours showed recent and rapid
      neurological deterioration after a protracted existence. Papilloedema, lower
      cranial nerve involvement, facial paraesthesias and preoperative hydrocephalus
      were significantly more in cystic tumours. Total excision was achieved in 38 of
      the solid and 18 of the cystic tumours. VIIth nerve preservation was higher in
      the cystic lesions [solid 33/40 (82.5%), cystic 21/22 (95.4%)]. Myxoid
      degeneration, lobular growth patterns and cellular atypia were more prominent in
      the cystic variants. The giant vestibular schwannomas were associated with a
      higher incidence of cystic degeneration than has been reported for smaller
      tumours in literature. In cystic lesions, VIIth nerve preservation was higher due
      to early decompression of the lesion that facilitated in early identification of
      the VIIth nerve, except in patients with type C cystic tumour.

PMID- 18803081
TI  - Delayed cervical spinal cord tethering following tonsillar resection for Chiari
      malformation.
AB  - Although tethering of the spinal cord in the lumbosacral region, particularly
      following repair of congenital anomalies, such as myelomeningocele, is a well
      known phenomenon, only sporadic reports of tethering along the rest of the
      neuraxis, including the hindbrain, cervical and thoracic spinal cord have been
      documented. In this report, we describe a woman who developed symptoms related to
      tethering of the cervical spinal cord 5 years after suboccipital decompressive
      surgery of the posterior fossa for Chiari I malformation. The authors discuss the
      diagnosis, treatment, and postoperative course of this entity.

PMID- 18803082
TI  - Endocrine evaluation of pituitary tumours.
AB  - This paper aims to provide a framework for understanding the investigations and
      management of pituitary adenomas from an endocrinologists viewpoint. The
      commonest problems, as well as the more controversial issues, are discussed and
      relevant, interesting papers on the topic are highlighted.

PMID- 18803083
TI  - Surgical pearls.
AB  - While endoscopic surgery is largely replacing microsurgery, many of the
      principles of trans-sphenoidal surgery are common to both techniques. For the
      novice surgeon there are many potential pitfalls that can, however, be avoided by
      attention to detail and careful planning. This article provides a practical
      overview from one surgeon's extensive experience.

PMID- 18803085
TI  - Risk factors and mechanisms of anaphylactoid reactions to acetylcysteine in
      acetaminophen overdose.
AB  - BACKGROUND: Adverse effects to N-acetylcysteine (NAC) are well recognized, but
      their etiology and incidence are unclear. METHODS: The nature and severity of
      adverse effects were prospectively studied in 169 patients and potential reaction
      mediators studied in 22 patients. RESULTS: Adverse effects were minimal in 101
      (59.8%), moderate in 51 (30.2%), and severe in 17 (10.1%). Features were nausea
      (70.4%), vomiting (60.4%), flushing (24.9%), pruritus (20.1%), dyspnea (13.6%),
      chest pain (7.1%), dizziness (7.7%), fever (4.7%), wheeze and bronchospasm
      (7.1%), and rash and urticaria (3.6%). Serum acetaminophen concentration was
      lower in patients with severe adverse effects: median (IQR) 46 mg/L (0 to 101
      mg/L), moderate 108 mg/L (54 to 178 mg/L), and minimal 119 mg/L (77 to 174 mg/L),
      p = 0.002. Family history of allergy and female gender were independent risk
      factors for adverse effects. Severity of adverse effects was associated with
      histamine release: AUC for change from baseline histamine was -6 ng/mL min (-60
      to 11 ng/mL min) in the minimal group, 26 ng/mL min (3-129 ng/mL min) in the
      moderate group, and 49 ng/mL min (21-68 ng/mL min) in the severe group (p =
      0.01). There was no increase in tryptase and no differences between groups for
      NAC concentrations or hemostatic and inflammatory variables (factors II, VII, IX,
      X, vWF, tPA, IL6, and CRP). CONCLUSION: Severity of adverse effects correlates
      with the extent of histamine release. Histamine release appears independent of
      tryptase suggesting a non-mast cell source. Acetaminophen is protective against
      adverse effects of NAC, and mechanisms by which acetaminophen might lessen
      histamine release require further attention.

PMID- 18803086
TI  - Evaluation of the patterns of potentially toxic exposures in Mississippi
      following Hurricane Katrina.
AB  - OBJECTIVE: To describe the changes in the frequency of selected toxic exposures
      reported to the state poison control center following Hurricane Katrina. METHODS:
      The numbers of selected exposures reported to the Mississippi Poison Control
      Center at 0-2 weeks, 3-4 weeks, and 5-12 weeks following Hurricane Katrina were
      compared to those for the same time periods in the previous 3 years. Absolute
      numbers of exposures and odds ratios with confidence intervals were used for
      comparison. RESULTS: In the first 2 weeks following Hurricane Katrina, there were
      44 reported gasoline exposures compared to 7 expected, 8 lamp oil exposures
      compared to 1 expected, and seven carbon monoxide exposures compared to 1
      expected. Only gasoline exposures remained elevated in the second 2 weeks period
      following the hurricane. Lamp oil exposures were elevated during the 5-12 week
      recovery period. There was no increase in the frequency of exposures to household
      cleaning agents, food poisoning, pediatric exposures, drug-related suicide
      events, bites and stings, or venomous snakebites. CONCLUSIONS: The most common
      toxic exposures following Hurricane Katrina were related to the lack of typical
      energy sources, electricity, and gasoline.

PMID- 18803087
TI  - Fatal injury in eastern Sri Lanka, with special reference to cardenolide self
      poisoning with Cerbera manghas fruits.
AB  - OBJECTIVE: Self-poisoning with plant seeds or fruits is a common method of self
      harm in South Asia. While most deaths follow ingestion of Thevetia peruviana
      (yellow oleander) seeds, other plants are locally common. During review of fatal
      injuries seen in a teaching hospital in eastern Sri Lanka, we noted cases of
      fatal self-poisoning with Cerbera manghas (sea mango, pink eyed cerbera, odollam
      tree) fruits. METHODS: We reviewed the post-mortem records of the Batticaloa
      Teaching Hospital and extracted data on all cases of fatal injury. RESULTS:
      During 2001 and 2002, 315 post mortems for injury were performed in Batticaloa
      Teaching Hospital. Intentional self-harm was responsible for 48.6% of cases.
      While T. peruviana was responsible for 33 deaths, C. manghas self-poisoning
      caused seven deaths. C. manghas cases had typical features of cardenolide
      poisoning with cardiac dysrhythmias and hyperkalemia. In the absence of pacing
      facilities and anti-digoxin Fab, management involved administration of atropine
      and of insulin and dextrose to lower serum potassium concentrations. CONCLUSIONS:
      C. manghas self-poisoning has only previously been reported from Kerala and Tamil
      Nadu in south India. While uncommon in other parts of Sri Lanka, it has become a
      common method of self-harm in one east coast district, accounting for 20% of
      fatal self-harm with plants in one hospital. Management was inadequate with the
      available resources, emphasising the need for an affordable antitoxin for plant
      cardenolide poisoning.

PMID- 18803088
TI  - Syrian rue tea: a recipe for disaster.
AB  - Peganum harmala, commonly called "Syrian rue," is native to countries around the
      Mediterranean sea and western United States. Known for its sedative effects when
      consumed by farm animals, its seeds have stimulant and hallucinogenic effects at
      low doses (3-4 g when eaten) in humans. Its active ingredients harmaline and
      harmine have monoamine oxidase inhibitor properties. A 41-year-old female
      prepared a hot drink by boiling approximately 100 g of P. harmala seeds in water
      (10-20 times the recommended dose for "calming one's nerves"). Upon presentation
      to the emergency department, she was unconscious and had hypertension,
      tachycardia, and tachypnea. Hepatic and renal function markers were grossly
      elevated. After intubation, she improved with supportive care over the course of
      five days. Her level of consciousness, renal and hepatic markers gradually
      returned to normal. Poisoning with high doses of Peganum harmala can be life
      threatening, although patients usually recover with supportive therapy alone.

PMID- 18803089
TI  - Measuring team skills in crime scene investigation: exploring ad hoc teams.
AB  - The purpose of this study was to measure the team skills of operational crime
      scene examiners (CSEs). The techniques used were based on established methods and
      helped to gain a greater understanding of the domain of forensic investigation.
      The research begins with a hierarchical task analysis and then adapts pre
      established methods for measuring the performance of CSEs in four UK Police
      Forces. The process supports comparison between prescribed methods of 'good
      practice' and real world practice. This has allowed the identification of the
      distributed skills and tasks of the CSE. Using Annett et al.'s HTA(T), crime
      scene examination can be categorised and the communications and coordination
      structures occurring between teams investigating a burglary considered. This
      makes it possible to generalise the method to situations involving ad hoc teams.

PMID- 18803090
TI  - Augmenting understanding of the relationship between situation awareness and
      confidence using calibration analysis.
AB  - The present study represents a preliminary examination of the relationship
      between situation awareness (SA) and confidence within a distributed information
      sharing environment using the calibration methodology. The calibration
      methodology uses the indices of calibration, resolution and over/under-confidence
      to examine the relationship between the accuracy of the responses and the degree
      of confidence that one has in these responses, which leads to a measure of an
      operator's meta-SA. The results of this study revealed that, although the
      participants were slightly overconfident in their responses, overall they
      demonstrated good meta-SA. That is, the participants' subjective probability
      judgements corresponded to their pattern of SA response accuracy. It is concluded
      that the use of calibration analysis represents a better methodology for
      expanding our understanding of the relationship between SA and confidence and
      ultimately how this relationship can impact decision-making and performance in
      applied settings than can be achieved by examining SA measures alone.

PMID- 18803091
TI  - Use of pressure insoles to compare in-shoe loading for modern running shoes.
AB  - The primary objective of this paper was to compare in-shoe loading for different
      models of running shoe using measurements of force distribution. It was
      hypothesised that a shoe designed with minimal focus on cushioning would
      demonstrate significantly higher peak forces and rates of loading than running
      shoes designed with cushioning midsoles. Loading was compared using in-shoe peak
      forces for six footwear conditions. It was found that peak rate of loading at the
      heel provided clear distinctions between shoes. In support of the study
      hypothesis, the shoe with minimal focus on cushioning had a significantly higher
      rate of loading than all but one of the other test shoes. Data collected for
      midfoot and forefoot areas of the foot highlighted the importance of considering
      loading across the foot surface. The results of the present study demonstrate
      that pressure insoles provide a useful tool for the assessment of loading across
      the foot plantar surface for different footwear conditions. There are numerous
      models of running shoe for individuals to select from, with limited information
      available regarding the performance of the shoes during running. The current
      study demonstrates differences in loads across the foot plantar surface during
      running, indicating differences in performance for different footwear models.

PMID- 18803092
TI  - The effects of a lower body exoskeleton load carriage assistive device on limits
      of stability and postural sway.
AB  - The study investigated the effects of using a lower body prototype exoskeleton
      (EXO) on static limits of stability and postural sway. Measurements were taken
      with participants, 10 US Army enlisted men, standing on a force platform. The men
      were tested with and without the EXO (15 kg) while carrying military loads of 20,
      40 and 55 kg. Body lean to the left and right was significantly less and postural
      sway excursions and maximal range of movement were significantly reduced when the
      EXO was used. Hurst values indicated that body sway was less random over short
      term time intervals and more random over long-term intervals with the EXO than
      without it. Feedback to the user's balance control mechanisms most likely was
      changed with the EXO. The reduced sway and relatively small changes in sway with
      increasing load weights suggest that the EXO structure may have functioned to
      provide a bracing effect on the body.

PMID- 18803093
TI  - Little effect of transfer technique instruction and physical fitness training in
      reducing low back pain among nurses: a cluster randomised intervention study.
AB  - The aim of this study was to evaluate the effect of a transfer technique
      education programme (TT) alone or in combination with physical fitness training
      (TTPT) compared with a control group, who followed their usual routine. Eleven
      clinical hospital wards were cluster randomised to either intervention (six
      wards) or to control (five wards). The intervention cluster was individually
      randomised to TT (55 nurses) and TTPT (50 nurses), control (76 nurses). The
      transfer technique programme was a 4-d course of train-the-trainers to teach
      transfer technique to their colleagues. The physical training consisted of
      supervised physical fitness training 1 h twice per week for 8 weeks. Implementing
      transfer technique alone or in combination with physical fitness training among a
      hospital nursing staff did not, when compared to a control group, show any
      statistical differences according to self-reported low back pain (LBP), pain
      level, disability and sick leave at a 12-month follow-up. However, the individual
      randomised intervention subgroup (transfer technique/physical training)
      significantly improved the LBP-disability (p = 0.001). Although weakened by a
      high withdrawal rate, teaching transfer technique to nurses in a hospital setting
      needs to be thoroughly considered. Other priorities such as physical training may
      be taken into consideration. The current study supports the findings of other
      studies that introducing transfer technique alone has no effect in targeting LBP.
      However, physical training seems to have an influence in minimising the LBP
      consequences and may be important in the discussion of how to prevent LBP or the
      recurrence of LBP among nursing personnel.

PMID- 18803094
TI  - A neural network model for predicting postures during non-repetitive manual
      materials handling tasks.
AB  - Posture prediction can be useful in facilitating the design and evaluation
      processes for manual materials handling tasks. This study evaluates the ability
      of artificial neural network models to predict initial and final lifting postures
      in 2-D and 3-D scenarios. Descriptors for the participant and condition of
      interest were input to the models; outputs consisted of posture-defining joint
      angles. Models were trained with subsets of an existing posture database before
      predictions were generated. Trained models predictions were then evaluated using
      the remaining data, which included conditions not presented during training.
      Prediction errors were consistent across these data subsets, suggesting the
      models generalised well to novel conditions. The models generally predicted whole
      body postures with per-joint errors in the 5 degrees -20 degrees range, though
      some errors were larger, particularly for 3-D conditions. These models provided
      reasonably accurate predictions, even outperforming some computational approaches
      previously proposed for similar purposes. Suggestions for future refinement of
      such models are presented. The models in this investigation provide a means to
      predict initial and final postures in commonly occurring manual materials
      handling tasks. In addition, the model structures provide information about
      potential lifting strategies that may be used by individuals with particular
      anthropometry or strength characteristics.

PMID- 18803095
TI  - Energy cost and mechanical efficiency of riding a human-powered recumbent
      bicycle.
AB  - When dealing with human-powered vehicles, it is important to quantify the
      capability of converting metabolic energy in useful mechanical work by measuring
      mechanical efficiency. In this study, net mechanical efficiency (eta) of riding a
      recumbent bicycle on flat terrain and at constant speeds (v, 5.1-10.0 m/s) was
      calculated dividing mechanical work (w, J/m) by the corresponding energy cost
      (C(c), J/m). w and C(c) increased linearly with the speed squared: w = 9.41 +
      0.156 . v(2); C(c) = 39.40 + 0.563 . v(2). eta was equal to 0.257 +/- 0.0245,
      i.e. identical to that of concentric muscular contraction. Hence, i) eta seems
      unaffected by the biomechanical arrangement of the human-vehicle system; ii) the
      efficiency of transmission seems to be close to 100%, suggesting that the
      particular biomechanical arrangement does not impair the transformation of
      metabolic energy in mechanical work. When dealing with human-powered vehicles, it
      is important to quantify mechanical efficiency (eta) of locomotion. eta of riding
      a recumbent bicycle was calculated dividing the mechanical work to the
      corresponding energy cost of locomotion; it was practically identical to that of
      concentric muscular contraction (0.257 +/- 0.0245), suggesting that the power
      transmission from muscles to pedals is unaffected by the biomechanical
      arrangement of the vehicle.

PMID- 18803096
TI  - The role of contextual factors for musculoskeletal disorders in the New Zealand
      meat processing industry.
AB  - Musculoskeletal disorders (MSD) are the leading cause of occupational injury
      internationally. In New Zealand, the highest incidence of MSD is in meat
      processing, accounting for over half the injury compensation costs for the
      sector. MSD in meat processing have proven highly resistant to physical, micro
      level interventions, suggesting a new approach is required. This paper reports on
      part of a 2-year study looking at MSD in the New Zealand meat processing
      industry. The qualitative study involved interviews with 237 workers, management,
      union and safety personnel in 28 processing sites. These data were summarised
      into a list of contextual factors, which, it is postulated, may create conditions
      under which greater exposure to physical and psychosocial factors can occur in
      meat processing. Some of the contextual factors are recognised as problematic by
      the industry, but have not previously been associated with MSD risk. The paper
      concludes by reflecting on conducting MSD research with a focus on contextual
      factors and how this may influence MSD prevention. The manuscript provides
      industry-based data on MSD risk and outlines the approach used in its collection.
      Identifying contextual factors and understanding their role in creating MSD risk
      may help improve the acceptance and effectiveness of MSD interventions in
      industry.

PMID- 18803097
TI  - Wrist strength is dependent on simultaneous power grip intensity.
AB  - The effect of grip activities on wrist flexion/extension strength was examined.
      Twelve healthy subjects performed maximum wrist flexion/extension exertions with
      one of five levels of simultaneous grip effort: minimum effort; preferred effort;
      30%, 60% and 100% maximum voluntary contraction. As grip force increased from the
      minimum to the maximum effort, average wrist flexion strength increased 34% and
      average wrist extension strength decreased 10%. It appears that the finger flexor
      tendons on the volar aspect of the wrist act agonistically in wrist flexion and
      act antagonistically to wrist extension. When an object gripped by the hand is
      fragile or uncomfortable, the reduced finger flexor activity will limit wrist
      flexion strength. Gripping a slippery object that requires high grip effort will
      result in reduced wrist extension strength. Grip force should be controlled
      during measurement of wrist flexion or extension strength. When analysing a task
      that involves both grip and wrist exertions, use of grip/wrist strength values
      that were measured during grip exertions only, or wrist exertions only, may
      incorrectly estimate the true grip/wrist strength, as grip and wrist activities
      significantly interact with each other as demonstrated in this paper.

PMID- 18803098
TI  - Infrared imaging of the anterior deltoid during overhead static exertions.
AB  - Infrared imaging has been used to detect the presence of neuromuscular disorders
      of the cervical spine and upper extremities. Despite diagnostic uses, evaluative
      or prognostic uses of thermography are limited. The objective of this study was
      to quantify surface temperature changes over the anterior deltoid and evaluate
      efficacy of thermography as an assessment tool. Surface temperature, discomfort
      ratings and endurance time were quantified during overhead static exertions until
      exhaustion at two work loads (15 and 30% maximum voluntary contraction) and
      shoulder angles (90 degrees and 115 degrees ). Ten participants free of
      confounding conditions participated in the study. The 90 degrees shoulder angle
      and 30% exertion level resulted in significantly faster thermal image rates of
      change, shorter endurance times and faster perceived discomfort increases.
      Thermography readings were more sensitive to changes in shoulder posture than
      load changes. This study provides preliminary evidence that thermography may be a
      useful exposure assessment tool. There is a need for new evaluation tools to
      quantify risk factor exposure for injury. Thermography was sensitive to changes
      in task loadings, illustrating its potential use for risk assessment.
      Specifically, changes in observed blood flow patterns during task performance are
      likely to conform to known physiological responses to injury.

PMID- 18803102
TI  - Pharmacologic treatment of disturbed sleep in the elderly.
AB  - Disturbed sleep is common in the elderly, who, as a group, take a
      disproportionately large number of hypnotic medications. Benzodiazepine
      hypnotics, as well as the newer benzodiazepine receptor agonists, are the primary
      treatments for these late-life sleep disorders and are effective and safe when
      used within recommended prescribing guidelines. The elderly also receive other
      psychiatric medications to induce sleep, although these are off-label uses not
      well supported by research literature. There is also no literature support for
      the use of over-the-counter sleep preparations, although both melatonin and a
      melatonin receptor agonist appear to be moderately effective and safe.
      Prescribing guidelines for the elderly continue to emphasize short-term, low-dose
      use, with short-half-life medications. Hypnotic drugs should be used in
      conjunction with nonmedication treatments, including appropriate sleep hygiene
      practice, and treatment of other medical or psychiatric causes of disturbed
      sleep.

PMID- 18803103
TI  - Sleep in the elderly: normal variations and common sleep disorders.
AB  - The most common complaints of older adults concern their difficulty initiating or
      maintaining sleep, which results in insufficient sleep and an increased risk of
      falls, difficulty with concentration and memory, and overall decreased quality of
      life. Difficulties sleeping are not, however, an inevitable part of aging.
      Rather, the sleep complaints are often comorbid with medical and psychiatric
      illness, associated with the medications used to treat those illnesses, or the
      result of circadian rhythm changes or other sleep disorders. Health care
      professionals specializing in geriatrics need to learn to recognize the different
      causes of sleep disturbances in this population and to initiate appropriate
      treatment. Nonpharmacological treatment techniques are discussed; pharmacological
      treatments are discussed in a companion article.

PMID- 18803104
TI  - Sleep-dependent memory processing.
AB  - While the functions of sleep remain largely unknown, one exciting hypothesis is
      that sleep contributes importantly to processes of memory and brain plasticity.
      Over the last decade, a large body of work has provided substantive evidence
      supporting this role of sleep in what is becoming known as sleep-dependent memory
      processing. This review offers a summary of these data, focusing specifically on
      the role of sleep in (1) memory encoding, (2) memory consolidation (along with
      the brain basis of this process), and (3) neural plasticity. The clinical
      ramifications of such findings are also explored.

PMID- 18803105
TI  - Neurosyphilis, malaria, and the discovery of antipsychotic agents.
AB  - Four of the most disabling human diseases are syphilis, malaria, schizophrenia,
      and manic-depressive illness. The history of the development of treatments for
      these seemingly unrelated disorders intersects at several points. Treatment of
      tertiary cerebral syphilis (general paresis) by inducing fever with malaria led
      to a Nobel Prize. Although attempts to synthesize quinine, a plant product
      effective against malaria, failed, these efforts encouraged industrial organic
      chemists to synthesize many useful substances, including dyes, antibiotics, and
      antihistamines. The aniline-derived dye methylene blue was a member of a new
      class of polycyclic chemicals, the phenothiazines. Efforts to modify
      phenothiazines to find an antimalarial agent also failed but led to novel
      antiemetic-sedative antihistamines, including promethazine, promazine, and
      eventually chlorpromazine--the first effective treatment for schizophrenia and
      mania. Chlorpromazine has antipsychotic and antimanic properties, and it
      revolutionized the therapeutics of psychotic illnesses.

PMID- 18803106
TI  - "Narcotics helped, I thought." Recurrent traumatization and recovery from drug
      dependence.

PMID- 18803107
TI  - Detection and identification of baculovirus pesticides by multitemperature single
      strand conformational polymorphism.
AB  - The method of single-strand conformational polymorphism (SSCP) was modified in
      our laboratories for the characterization of baculoviruses, insect viruses with
      great potential for use as bioinsecticides in biological protection programs. A
      series of primers were synthesized after the comparison of the polyhedrin gene
      sequences of over 20 baculoviruses. Polyhedrin is a highly conserved protein
      which is responsible for the persistence of the virus in the environment.
      Universal primers were designed which could be used in polymerase chain reactions
      (PCR) containing genomic DNA from an array of nucleopolyhedrosis viruses (NPVs)
      including these which are used as biopesticides against important pests of
      forests and crops, such as Anticarsia gemmatalis, Spodoptera frugiperda,
      Lymantria dispar, Lymantria monacha and many others. PCR products were denatured
      and subjected to single-strand DNA electrophoresis at variable temperatures
      (MSSCP) where, after silver staining, they gave ssDNA band patterns
      characteristic for each baculovirus species. This technique can be potentially
      applied to detect baculoviruses in insects collected in the field, as well as to
      plant tissues and the excrements or bodies of predators without need for
      sequencing the PCR products. Sometimes MSSCP can be used not only for species
      determination but also as an indication of genomic variability which can be
      related to infectivity.

PMID- 18803108
TI  - Photochemical degradation of methylparathion in the presence of humic acid.
AB  - Photochemical degradation of methylparathion (O,O,-dimethyl O-4
      nitrophenylphosphorothioate) in the presence of humic acid between pH 2 and 7 was
      monitored by differential pulse polarography. Humic acid was not electro-active
      under the experimental conditions used in this study. Only the pesticide and its
      main degradation product at pH 2 exhibited polarographic signals. Photolysis of
      methylparathion in acid media was sensitized by humic acid since the pesticide
      did not degrade in the absence of this compound. Methylparathion degradation in
      the presence of humic acid was observed at each of the studied pHs. The reaction
      was first-order with rate constant values ranging from 2 x 10(-3) to 6.3 x 10(-3)
      min(-1).

PMID- 18803109
TI  - Photocatalytic degradation of the herbicide pendimethalin using nanoparticles of
      BaTiO3/TiO2 prepared by gel to crystalline conversion method: a kinetic approach.
AB  - Photocatalytic degradation of the herbicide, pendimethalin (PM) was investigated
      with BaTiO3/TiO2 UV light system in the presence of peroxide and persulphate
      species in aqueous medium. The nanoparticles of BaTiO3 and TiO2 were obtained by
      gel to crystallite conversion method. These photo catalysts are characterized by
      energy dispersive x-ray analysis (EDX), scanning electron microscope (SEM), x-ray
      diffraction (XRD), and Brunauer-Emmett-Teller (BET) adsorption isotherm and
      reflectance spectral studies. The quantum yields for TiO2 and BaTiO3 for the
      degradation reactions are 3.166 Einstein m(-2) s(-1) and 2.729 Einstein m(-2) s(
      1) and catalytic efficiencies are 6.0444 x 10(-7) mg(-2)h(-1)L2 and 5.403 x 10(
      7) mg(-2)h(-1)L2, respectively as calculated from experimental results. BaTiO3
      exhibited comparable photocatalytic efficiency in the degradation of
      pendimethalin as the most widely used TiO2 photocatalyst. The persulphate played
      an important role in enhancing the rate of degradation of pendimethalin when
      compared to hydrogen peroxide. The degradation process of pendimethalin followed
      the first-order kinetics and it is in agreement with Langmuir-Hinshelwood model
      of surface mechanism. The reason for high stability of pendimethalin for UV
      degradation even in the presence of catalyst and oxidizing agents were explored.
      The higher rate of degradation was observed in alkaline medium at pH 11. The
      degradation process was monitored by spectroscopic techniques such as ultra
      violet-visible (UV-Vis), infrared (IR) and gas chromatography mass spectroscopy
      (GC-MS). The major intermediate products identified were: N-propyl-2-nitro-6
      amino-3, 4-xylidine, (2, 3-dimethyl-5-nitro-6-hydroxy amine) phenol and N-Propyl
      3, 4-dimethyl-2, 6-dinitroaniline by GC-MS analysis and the probable reaction
      mechanism has been proposed based on these products.

PMID- 18803110
TI  - Photooxidative removal of the herbicide Acid Blue 9 in the presence of hydrogen
      peroxide: modeling of the reaction for evaluation of electrical energy per order
      (E EO).
AB  - The present work deals with photooxidative removal of the herbicide, Acid Blue 9
      (AB9), in water in the presence of hydrogen peroxide (H2O2) under UV light
      illumination (30 W). The influence of the basic operational parameters such as
      amount of H2O2, irradiation time and initial concentration of AB9 on the
      photodegradation efficiency of the herbicide was investigated. The degradation
      rate of AB9 was not appreciably high when the photolysis was carried out in the
      absence of H2O2 and it was negligible in the absence of UV light. The
      photooxidative removal of the herbicide was found to follow pseudo-first-order
      kinetic, and hence the figure-of-merit electrical energy per order (E Eo) was
      considered appropriate for estimating the electrical energy efficiency. A
      mathematical relation between the apparent reaction rate constant and H2O2 used
      was applied for prediction of the electricity consumption in the photooxidative
      removal of AB9. The results indicated that this kinetic model, based on the
      initial rates of degradation, provided good prediction of the E Eo values for a
      variety of conditions. The results also indicated that the UV/H2O2 process was
      appropriate as the effective treatment method for removal of AB9 from the
      contaminated wastewater.

PMID- 18803111
TI  - Photodegradation of the herbicide penoxsulam in aqueous methanol and
      acetonitrile.
AB  - Penoxsulam is a triazolopyrimidine sulfonamide group of rice herbicide. The
      phototransformation of penoxsulam was studied under UV light (lambda max >or= 290
      nm) and sunlight in aqueous methanol and acetonitrile solvent system using TiO2
      as sensitizer. The rate of photodegradation of penoxsulam in different solvent
      systems followed first-order kinetics and calculated half-lives was found to be
      in the range of 51.89-73.41 h and 62.70-97.09 h for UV light and sunlight
      respectively in the presence or absence of sensitizer. From this study, a total
      of six photoproducts were identified and characterized on the basis of Q-Tof
      micromass spectral data. The plausible mechanism of phototransformation involved
      were hydrolysis, photo oxidation of the sulfonamide group, breaking of
      sulfonamide bond, loss of amino and sulfonic acid group.

PMID- 18803112
TI  - Degradation of diuron in aqueous solution by ozonation.
AB  - Degradation of diuron [3-(3,4-dichlorophenyl)-1,1-dimethylurea] in aqueous
      solution and the proposed degradation mechanism of diuron by ozonation were
      investigated. The factors that affect the degradation efficiency of diuron were
      examined. The generated inorganic ions and organic acids during the ozonation
      process were detected. Total organic carbon removal rate and the amount of the
      released Cl(-) increased with increasing ozonation time, but only 80.0% of the
      maximum theoretical concentration of Cl(-) at total mineralization was detected
      when initial diuron concentration was 13.8 mg L(-1). For N species, the final
      concentrations of NO3(-) and NH4+ after 60 min of reaction time were 0.28 and
      0.19 mg L(-1), respectively. The generated acetic acid, formic acid and oxalic
      acid were detected during the reaction process. The main degradation pathway of
      diuron by ozonation involved a series of dechlorination-hydroxylation,
      dealkylation and oxidative opening of the aromatic ring processes, leading to
      small organic species and inorganic species. The degradation efficiency of diuron
      increased with decreasing initial diuron concentration. Higher pH value, more
      ozone dosage, additive Na2CO3, additive NaHCO3 and additive H2O2 were all
      advantageous to improve the degradation efficiency of diuron.

PMID- 18803113
TI  - Biodegradation of insecticide carbofuran by Paracoccus sp. YM3.
AB  - A bacterium (Paracoccus sp. YM3) capable of degrading carbofuran was isolated
      from carbofuran-contaminated sludge. The strain was shown to metabolize
      carbofuran (50 mg L(-1)) to carbofuran-7-phenol in minimal salt medium within 6
      days in which the pesticide was the only source of carbon. Carbofuran and its
      main metabolite were analyzed by high performance liquid chromatography (HPLC).
      The addition of an other carbon source led to accelerated biodegradation. The
      relevant degrading-enzyme was intracellular and inducible. A tobacco
      hypersensitivity experiment showed that YM3 could eliminate carbofuran in soils
      effectively and safely. This is the first report of a Paracoccus sp. that could
      degrade carbofuran. The present study may provide a basis for biotreatment of
      wastewaters and bioremediation of carbofuran-contaminated soils.

PMID- 18803114
TI  - Impact of repeated pesticide applications on the binding and release of methyl
      14C-monocrotophos and U-ring labelled 14C-carbaryl to soil matrices under field
      conditions.
AB  - The dissipation of (O-methyl-14C) monocrotophos and U-ring labelled 14C-carbaryl
      was monitored for over two years in absence and presence of other insecticides
      using in situ soil columns. The dissipation of 14C-monocrotophos from soil
      treated with methomyl and carbaryl showed a faster rate of downward movement than
      in a control column tagged with the labelled insecticide alone. The same trend
      was observed in experiments with 14C-carbaryl that dissipated more readily in
      soil treated with non-labelled monocrotophos and methomyl. In the presence of
      other insecticides the percentage of bound residues was generally lower than in
      control experiments. The bound residues at the top of the column are released at
      a low rate under conditions prevailing in the field. The overall time required
      for dissipation of 50% of monocrotophos and carbaryl (t50) as estimated from
      control experiment was approximately 20 and 24 weeks, respectively. The data
      indicate that repeated applications of pesticides might enhance the release of
      14C-bound residues.

PMID- 18803115
TI  - Sorption of fenamiphos to different soils: the influence of soil properties.
AB  - Fenamiphos (0-ethyl-0(3-methyl-4-methylthiophenyl)-isopropylamido-phosphate) is a
      widely used nematicide and insecticide in bowling greens and agriculture, but
      information on its sorption including its metabolites is limited. Hence, the
      sorption of fenamiphos (nematicide) and its major degradation products fenamiphos
      sulfoxide (FSO) and fenamiphos sulfone (FSO2) were determined in thirteen
      contrasting soils collected from Australia and Ecuador. The sorption coefficients
      (Kd) exhibited a wide range of variation from 2.48 to 14.94 L/Kg for fenamiphos;
      from 0 to 7.42 L/Kg for FSO and from 0 to 9.49 L/Kg for FSO2. The sorption
      affinity of the three compounds for all soils tested was as follows: fenamiphos >
      fenamiphos sulfone > fenamiphos sulfoxide. The results showed that the sorption
      of fenamiphos and its metabolites in some soils is very low, and in one case is
      nonexistant for the metabolites. This is of particular concern as due to its low
      sorption coefficient, the compound could easily migrate and contaminate water
      bodies. Fenamiphos and its oxidation products have been reported to be highly
      toxic to aquatic invertebrates and therefore, the information generated in this
      study assumes great importance in the risk assessment of fenamiphos and its
      metabolites in the environment.

PMID- 18803116
TI  - Sedimentation and seasonal variation of hexachlorocyclohexanes in sediments in a
      eutrophic lake, China.
AB  - Hexachlorocyclohexane (HCH) concentrations in sediments and sediment trap fluxes
      of particulate organic carbon and HCHs were measured bi-weekly from March 31 to
      October 18, 2006 in an urban eutrophic lake in Tianjin, China, in order to
      investigate sedimentation and seasonal variation of HCHs in sediments. HCH
      concentrations (dry weight basis) ranged from 2.2 to 20.2 ng/g (mean 7.7 ng/g) in
      surface sediments and from 26.6 to 972.7 ng/g (mean 187.0 ng/g) in settling
      particles, respectively. A clear seasonal variation in HCH sedimentation and HCH
      concentrations in sediments was observed. The maximal HCH deposition occurred
      following a spring phytoplankton bloom. The average flux of HCHs to sediment was
      approximately 21-fold higher in April to mid-June as compared to late June to
      October. This was attributed to the high vertical fluxes at the end of the spring
      phytoplankton bloom. The maximum values of HCH concentrations in sediments were
      observed in mid-June to late July. Concentrations of HCHs in sediments from the
      eutrophic lake were well-correlated with organic carbon contents in sediments.
      The annual sediment trap flux of HCHs in the eutrophic lake, which was estimated
      using data obtained in the eutrophic lake, was 117 microg/m2 yr, about 72% of
      which was attributed to the sedimentation corresponding to spring bloom
      phytoplankton deposition in late May to mid-June. The high sediment trap flux of
      HCHs in the eutrophic lake was related to serious local contamination.

PMID- 18803117
TI  - Factors affecting the removal of aflatoxin M1 from food model by Lactobacillus
      and Bifidobacterium strains.
AB  - This paper describes the ability of six dairy strains of Lactobacillus and
      Bifidobacterium to remove aflatoxin M1 (AFM 1) from phosphate-buffered saline
      (PBS) and reconstituted milk. Bacteria were incubated in both PBS and
      reconstituted milk containing 5, 10 and 20 ng mL(-1) for 0, 4 and 24 h at 37
      degrees C. After centrifugation the concentration of AFM 1 was determined in the
      supernatant fraction using high-performance liquid chromatography. The binding
      abilities of AFM 1 by viable (10(8) CFU mL(-1)) and heat-killed Lactobacillus and
      Bifidobacterium strains in PBS ranged from 10.22 to 26.65% and 14.04 to 28.97%,
      respectively. Similarly, AFM 1-binding capacity in reconstituted milk was found
      to range from 7.85 to 25.94% and from 12.85 to 27.31% for viable and heat-killed
      bacteria, respectively within 4 h. While B. bifidum Bb 13 was the best binder,
      the poorest removal was achieved by L. acidophilus NCC 68. Binding was
      reversible, and a small proportion of AFM 1 was released back into the solution.
      The toxin concentration and incubation period had no effect on the removal of AFM
      1 by bacteria both in PBS and reconstituted milk.

PMID- 18803118
TI  - Nickel-induced blood biochemistry alterations in hens after an experimental
      peroral administration.
AB  - The purpose of this study was to determine certain blood biochemical parameters
      in hens of Isa Brown breed (n = 20) after nickel administration. Animals were
      divided into four groups (K, P1, P2, P3). Experimental hens (n = 5; in each
      group) received nickel (NiCl2) as peroral administration in drinking water in
      various doses (P1 - 0.02 g NiCl2/L; P2 - 0.2 g NiCl2/L; P3 - 2.0 g NiCl2/L of
      drinking water) for 28 days. The last group - K (n = 5) was the control,
      receiving no nickel. Biochemical parameters of mineral profile (calcium;
      phosphorus; magnesium; sodium; potassium) and of energy and enzymatic profile
      [(glucose; total cholesterol; total proteins; triglycerides; alanine
      aminotransferase (ALT) aspartate aminotransferase (AST) gamma glutamyl
      transferase (GGT) and glutamatdehydrogenase (GLDH)] were analyzed in blood serum
      on Day 0, 7, 14, 21 and 28 of the experiment. Average levels of mineral
      metabolism parameters were relatively stable apart from calcium. The evaluation
      registered a significant decrease in calcium during the experiment mainly in the
      group with highest nickel concentration in drinking water. No significant
      differences were detected between groups in energy and enzymatic profile apart
      from the concentrations of ALT on Day 7. In conclusion, there were significant
      associations between nickel levels and calcium and ALT in blood serum of the
      hens. No significant differences were detected in other biochemical parameters of
      mineral profile (P, Mg, Na, K) and energy and enzymatic profile (glucose, total
      cholesterol, total proteins, triglycerides, AST, GGT and GLDH) after nickel
      administration. Our results may contribute to an evaluation of reference levels
      of analyzed parameters, to monitor the health and nutritional status of hens. In
      this study also the negative effect of nickel mainly on calcium metabolism was
      detected.

PMID- 18803119
TI  - Obtundation and seizure following ondansetron overdose in an infant.
AB  - INTRODUCTION: Ondansetron, an increasingly prescribed 5-HT(3) antagonist used in
      the management of nausea and vomiting of various etiologies, has a well
      established safety profile in therapeutic use. However, little is known about its
      effects in the setting of an overdose. We describe the first case of severe
      toxicity in an infant who unintentionally ingested a large quantity of
      ondansetron. CASE REPORT: A 12-month-old infant who ingested seven to eight
      tablets of his mother's Zofran (ondansetron) ODT 8 mg rapidly developed
      obtundation and myoclonic movements. While treated by health care providers, he
      developed seizures, hepatotoxicity, QTc prolongation, and a serotonin syndrome
      that required endotracheal intubation and intensive care unit management. His
      clinical status improved over the course of 24 h with supportive care, and he was
      discharged to home with no sequelae. DISCUSSION: With the increasing popularity
      of ondansetron among health care providers, particularly for the control of
      nausea in pregnant women, toddlers in the household may become inadvertently
      exposed to ondansetron toxicity. This case portrays that, despite the safety of
      this agent in therapeutic dosage, severe toxicity may be seen in excessive
      amounts, particularly in infants. CONCLUSION: Health care providers should
      recognize the risk for acute toxicity following ondansetron overdose,
      particularly in infants and toddlers.

PMID- 18803120
TI  - A pilot study of occupational envenomations in North American zoos and aquaria.
AB  - OBJECTIVE: To characterize occupational envenomations from exotic and native
      creatures, we surveyed North American zoos and aquaria. METHODS: Survey
      questionnaires were mailed to curators at 216 zoos/aquaria which are accredited
      by the Association of Zoos and Aquariums (AZA) and listed on the AZA website.
      Reptile curators were asked to complete the zoo surveys. The questions addressed
      the number and types of bites, availability of antivenom (AV) on the premises,
      and sources of general information about envenoming. Responses were kept
      anonymous. RESULTS: A total of 216 surveys were mailed. The response rate was 58%
      for this pilot research project. Twenty-six (21%) of responding institutions
      replied that they had at least one incident of bite from a venomous species in
      the last 10 years. Species of animals included a variety of native and exotic
      terrestrial and marine species. There were no deaths or serious outcomes reported
      as complications of these incidents. Less than one-third of responding
      institutions reported having AVs on-site for medical use in case of
      envenomations. A variety of information sources, including internally developed
      protocols and poison center resources, were reported as sources of envenoming
      information for respondents. CONCLUSIONS: Clinicians and toxicologists should be
      prepared to care for cases of envenomations from exotic zoo or aquarium species
      such as the ones identified in this survey in their practice regions.

PMID- 18803121
TI  - [Animal models in the study of the glaucoma: past, present and future].

PMID- 18803122
TI  - [Autologous serum in the treatment of dry eye syndrome. Technological aspects].

PMID- 18803123
TI  - [Low dose photodynamic therapy for chronic central serous chorioretinopathy].

PMID- 18803124
TI  - [Agreement among ophthalmologists and primary care physicians in the evaluation
      of retinographies of diabetic patients].
AB  - PURPOSE: To assess the extent of agreement in the evaluation of non-mydriatic
      retinographies of diabetic patients among ophthalmologists and a group of primary
      care physicians with previous training. METHODS: The study was divided in two
      phases. In the first phase, the four participants were instructed in the
      interpretation of retinographies. The second phase involved the evaluation of
      1000 images of 200 patients, 100 without retinopathy and 100 with signs of
      diabetic retinopathy. The four participants had to decide if the images did or
      did not show evidence of diabetic retinopathy. Kappa index was used to assess the
      extent of agreement. A percentage disagreement of 15% with a precision of 5% (+/
      5%) with a confidence level of 95% was considered adequate. RESULTS: The
      percentage of coincident diagnoses among ophthalmologists and primary care
      physicians was between 89 and 97.5%. With respect to the assessment of the
      agreement, the kappa index was between 80 and 95%. In all cases the confidence
      interval was at least 85%. CONCLUSIONS: After an adequate training process, the
      reliability of evaluation of non-mydriatic retinographies of diabetic patients by
      primary care physicians was very high. This could allow the establishment of
      screening for diabetic retinopathy at the primary care level. Advantages of this
      system include a greater involvement of primary care physicians in the global
      management of diabetic patients and a lower demand for ophthalmic attention.

PMID- 18803125
TI  - [Detection of glaucoma using SisGlaTel: acceptability and satisfaction among
      participants, and problems detected].
AB  - PURPOSE: To evaluate the problems, and the degree of acceptability and
      satisfaction among participants in a telemedicine screening program. This study
      forms part of a global project for the design, implementation and evaluation of
      SisGlaTel funded by the Fondo de Investigaciones Sanitarias (Spain) and Pfizer
      Ophthalmics. METHOD: A telemedicine system was built based on a specific program
      written in JAVA. The remote station was located at a Primary Care Center.
      Participants signed an informed consent, and completed a questionnaire and
      undertook different tests (frequency doubling perimetry-FDT, confocal scanning
      laser tomografy-HRT and tonometry). Test results and problems detected were
      analysed. Ninety-nine subjects completed a satisfaction questionnaire after
      voluntarily participating in the screening program among an at-risk population.
      The questionnaire included 7 questions, four of which required participants to
      categorise their responses, ranging from very bad (1) to excellent (5), to
      questions about the screening program, its usefulness, the care received and the
      installations. RESULTS: Six hundred and forty-one at-risk subjects were examined.
      After 2 exams per eye, 22.3% (143) presented abnormal FDT and 4.2% (27) had
      pathologic HRT. One hundred percent of respondents affirmed they would
      participate again in a similar program. The mean qualification (SD) was 4.5
      (0.6), 4.5 (0.6), 4.8 (0.5), and 4.3 (0.7) for global opinion, usefulness, care
      and equipment. CONCLUSION: SisGlaTel allows integration of several diagnostic
      tests useful for glaucoma tele-screening. The global degree of satisfaction among
      participants was good.

PMID- 18803126
TI  - [Photodynamic therapy with verteporfin in choroidal neovascularization after
      refractive surgery].
AB  - PURPOSE: To analyze the results obtained with Photodynamic Therapy (PDT) to treat
      subfoveal and juxtafoveal Choroidal Neovascularization (CNV) in patients with
      high myopia corrected by Laser-Assisted in situ Keratomileusis (LASIK) or by
      implanting a Phakic Intraocular Lens (PIOL). METHODS: We analyzed the results
      from 14 highly myopic eyes corrected by LASIK (seven cases) or by PIOL
      implantation (seven cases), which later developed CNV and were treated by PDT
      with verteporfin. RESULTS: Mean Best Corrected Visual Acuity (BCVA) after
      refractive surgery was 0.45 SD 0.17 (range, 0.2 to 0.8), with residual spherical
      equivalent (RSE) -0.5 SD 1.8 D (range, 1 to 5.5 D). After CNV appearance, BCVA
      was 0.10 SD 0.19 (range, 0.025 to 0.7). CNV was treated in all cases by PDT
      (mean, 2.0 SD 0.8 treatments). After CNV closure, the mean BCVA improved up to
      0.22 SD 0.18 (range, 0.1 to 0.63) (RSE -1.4 SD 1.4 D, range, 0.5 to -4 D).
      Differences in RSE after refractive surgery and after PDT, and differences
      between BCVA after CNV appearance and final were not statistically significant
      (p=0.82 and p=0.06, respectively, Student's t test paired data). CONCLUSION: We
      consider that PDT is effective in achieving closure of CNV in myopic patients
      after refractive surgery without inducing changes in spherical equivalent.

PMID- 18803127
TI  - [Photodynamic therapy in retinal pigment epithelium detachment associated with
      long term central serous chorioretinopathy].
AB  - PURPOSE: To present a case of long term central serous corioretinopathy
      associated with chronic detachment of the retinal pigment epithelium (RPE) and
      the effect of photodynamic therapy on it. CASE CLINIC: We present the case of a
      46-year old man with long term chronic central serous chorioretinopathy (18 mo.)
      with chronic detachment of RPE in his left eye who underwent PDT with Verteporfin
      (Visudyne). BCVA improved from 0.7 to 1 and metamorphopsia disappeared within one
      month of treatment. The patient remained asymptomatic for a follow-up period of
      15 months. DISCUSSION: Choroidal hyperpermeability is found in central serous
      chorioretinopathy as a primary involvement factor. PDT with Verteporfin induces a
      transient reduction in choriocapilaris blood flow and can be used as treatment in
      cases of chronic central serous chorioretinopathy.

PMID- 18803128
TI  - [Descemet's membrane detachment as a complication of cataract surgery].
AB  - CASE: A case of Descemet's membrane detachment after cataract surgery
      successfully treated with an injection of sulphur hexafluoride 20% is presented.
      DISCUSSION: Possible pathogenic mechanisms and available therapeutic options are
      discussed. We highlight the need for prophylactic measures and the importance of
      an early detection to prevent further damage.

PMID- 18803129
TI  - [Circumscribed choroidal hemangioma treated with photodynamic therapy].
AB  - CLINICAL CASE: A 45-year-old male referred with a scotoma in the left eye of 2
      months' evolution. A peripapillary tumor was found, with a basal diameter of 7 mm
      and thickness 3.4 mm. It was diagnosed as a circumscribed choroidal hemangioma.
      It was decided to treat the patient using photodynamic therapy. After 4 sessions
      and 17 months follow-up, the patient remained asymptomatic and visual acuity was
      stable. There was evidence of subretinal fibrosis and no subretinal fluid was
      found. DISCUSSION: Photodynamic therapy is a good option for the treatment of
      circumscribed choroidal hemangioma given the minimal damage is causes to the
      adjacent retina.

PMID- 18803130
TI  - [Newborn chronic follicular conjunctivitis].
AB  - CASE REPORT: A case of chronic follicular conjunctivitis in an infant presenting
      with ptosis and dacryorrhea is reported. Polymerase chain reaction (PCR) test
      identified Chlamydia trachomatis as the causative agent. The patient was treated
      with topic and systemic erythromycin. The infection was probably transmitted
      during delivery. DISCUSSION: Chronic follicular conjunctivitis in infants is very
      uncommon in our environment. The most sensitive and specific diagnostic test is
      PCR. It is necessary to identify the original focus of infection and to provide
      specific treatment to all the carriers as soon as possible to avoid and prevent
      chronic complications.

PMID- 18803131
TI  - [Is cataract an opacification of the crystalline? (I). Study on medieval texts.
      1. Etymology and medical doctrine].

PMID- 18803132
TI  - [The true color blindness of Charles Meryon (1821-1868)].

PMID- 18803133
TI  - Selected mutations in the myosin binding protein C gene in the Polish population
      of patients with hypertrophic cardiomyopathy.
AB  - BACKGROUND: Mutations in the gene of myosin binding protein C (MYBPC3) are
      currently considered the most frequent cause of hypertrophic cardiomyopathy
      (HCM). AIM: To assess the frequency of selected mutations in MYBPC3 in the Polish
      population of HCM patients. METHODS: One hundred eighteen patients with HCM and
      118 healthy, age and sex-matched controls were screened for the presence of 14
      mutations of MYBPC3 using real time polymerase chain reaction. RESULTS: Five
      different mutations were found in six patients in the HCM group whereas no
      mutations were present in the control group. In three cases the mutations were
      missense (Arg502Gln, Cys566Arg, Asn755Lys) and in three cases terminal
      (Gln425ter, Gln1061ter in two unrelated probands). CONCLUSION: Mutations in
      MYBPC3 should be considered a frequent cause of HCM in Poland.

PMID- 18803134
TI  - Primary angioplasty in patients > or = 75 years old with ST-elevation myocardial
      infarction - one-year follow-up results.
AB  - BACKGROUND: Efficacy and safety of primary percutaneous coronary angioplasty
      (PCI) in elderly patients with acute ST-elevation myocardial infarction (STEMI)
      have not yet been definitely established because these patients were usually
      excluded from large randomised trials. AIM: To evaluate in-hospital and one-year
      outcome after primary PCI in elderly patients, and to assess clinical
      characteristics of this group. METHODS: The study population included 1061
      consecutive STEMI patients, mean age 60.6+/-17 years, treated with primary PCI.
      Clinical characteristics and results of 127 patients aged > or = 75 years were
      compared to the younger group. RESULTS: Elderly patients were more frequently
      female (48.4 vs. 23.6%, p <0.005) and diabetics (22.2 vs. 12.1%, p <0.02) and
      more frequently had renal and/or left ventricular failure (22.3 vs. 9.1%, and 9.1
      vs. 4.5%, p <0.005, respectively). In older patients less frequently stents were
      implanted and TIMI flow 3 was restored (65.1 vs. 78.8%, p <0.05 and 74.6 vs.
      84.7%, p <0.03). In-hospital mortality in older versus younger patients was 11.8
      vs. 3.0%, p <0.005. The incidence of in-hospital complications (stroke, major
      bleeding and reinfarction) was similar in both groups. The one-year mortality and
      MACE rates were higher in older patients (21.3 vs. 6.0% and 24.9 vs. 11.0%, p
      <0.0005). In multivariate analysis Killip class II-IV (OR 6.73; 95% CI 1.75
      25.97, p=0.006) and heart rate (OR 1.04; 95% CI 1.01-1.07, p=0.03) were
      independent predictors of one-year mortality in patients aged > or = 75 years.
      CONCLUSIONS: Primary PCI in older STEMI patients is associated with a favourable
      in-hospital and one-year outcome, although inferior to that seen in younger
      patients. The in-hospital complication rate is similar in the elderly and in
      younger patients.

PMID- 18803135
TI  - Internal carotid artery stenosis in patients with degenerative aortic stenosis.
AB  - BACKGROUND: In patients with severe degenerative aortic stenosis (DAS) the
      operative mortality risk is 3% for isolated aortic valve replacement (AVR), but
      it significantly increases in patients with concomitant coronary artery disease
      (CAD) and internal carotid artery stenosis (ICAS). AIM: To assess the frequency
      of ICAS > or = 50% and factors determining its occurrence in patients with severe
      calcified DAS referred for AVR. METHODS: The study included 104 patients (67
      men), aged 63.4+/-8.4 years, with symptomatic moderate-to-severe DAS (aortic
      valve area <1.5 cm2) undergoing coronary angiography prior to valve surgery. In
      all patients Doppler ultrasound of carotid arteries was performed with the
      assessment of lumen stenosis. RESULTS: Significant CAD, defined as at least one
      lumen reduction > or = 50% in a main coronary artery, was found in 44 (42.3%)
      patients and ICAS > or = 50% in 13 (12.5%) patients. Among patients with DAS, 12
      (27.3%) out of 44 patients with significant CAD and 1 (1.7%) out of 60 patients
      without CAD had ICAS > or = 50% (p <0.001). The frequency of ICAS > or = 50%
      increased with advancing CAD, occurring in 4 (25%) out of 16 patients with 1
      vessel CAD, 3 (25%) out of 12 with 2-vessel CAD and (31.3%) out of 16 patients
      with 3-vessel CAD (p <0.001). The independent ICAS predictors by multivariate
      regression analysis were identified as: concomitant CAD (p <0.001), diabetes
      (p=0.054), cigarette smoking (p=0.08) and decreased left ventricular ejection
      fraction (p=0.039). ICAS > or = 50% was found to be an independent predictor of
      CAD (p=0.002). CONCLUSIONS: ICAS > or = 50% occurs in 13% of patients with
      isolated DAS and in 27% of those with DAS and CAD. Independent ICAS risk factors
      were identified as CAD, diabetes and cigarette smoking. Duplex ultrasound of
      carotid arteries should be considered in patients with DAS and concomitant CAD
      prior to AVR.

PMID- 18803136
TI  - The association between SCN5A, KCNQ1 and KCNE1 gene polymorphisms and complex
      ventricular arrhythmias in survivors of myocardial infarction.
AB  - BACKGROUND: Post-MI patients are highly susceptible to sudden cardiac arrest
      (SCA) and sudden cardiac death (SCD) resulting from ventricular arrhythmia (VA).
      The search for new clinical predictors to identify those patients who are at the
      highest risk of these events is therefore essential. Numerous data indicate that
      the presence of polymorphisms and mutations in the cardiac ion channel genes
      SCN5A, KCNQ1 and KCNE1 might serve as such a predictor. Since genetic alterations
      in these genes underlie congenital long QT syndrome (LQTS), which is associated
      with an increased occurrence of arrhythmic complications and SCD, we decided to
      verify how alterations in these genes contribute to QT interval abnormalities and
      consequently to VA, SCA and SCD in post-MI patients. AIM: To detect single
      nucleotide polymorphisms (SNP) in SCN5A, KCNQ1 and KCNE1 of post-MI patients, and
      to assess whether they are related to electrophysiological markers of cardiac
      arrhythmia (QT interval) and the clinical course. METHOD: The study group
      consisted of 100 patients (27 females, mean age 69 years) with documented MI 3
      months before enrolment. All patients underwent baseline and (after 12 months)
      control examinations encompassing history, physical examination, basic laboratory
      analysis, resting 12-lead ECG, 24-hour 12-lead Holter ECG monitoring and
      echocardiography. Genetic tests were performed during baseline examination.
      RESULTS: In post-MI patients two exonic polymorphisms, H558R in SCN5A and S38G in
      KCNE1, and two intronic ones, in KCNQ1, were detected. H558R was associated with
      an increase in QT dispersion (QTd) at minimum and maximum heart rate and QT
      interval prolongation before premature ventricular beats (PVB), whereas S38G and
      intronic polymorphisms were related to an increase in QTd before PVB. None of the
      above polymorphisms was related to complex VA, SCA or SCD. CONCLUSION: The above
      polymorphisms were associated with abnormal repolarisation phase patterns in post
      MI patients, which manifested in QT interval prolongation and QTd increase. There
      was no relationship between these polymorphisms and complex VA, SCA or SCD. The
      results show that not only exonic alterations but also intronic ones may affect
      the phenotype.

PMID- 18803137
TI  - Renal artery stenosis in patients with coronary artery disease.
AB  - BACKGROUND: Renal dysfunction is an important factor of cardiovascular risk.
      Renal artery stenosis (RAS) is a potential cause of secondary hypertension and by
      renal ischemia may lead to progressive renal insuficiency. In RAS patients a
      significant increase in prevalence of coronary artery disease (CAD) as well as
      revascularisation rate and mortality rate was observed. AIM: To determine the
      prevalence of RAS in patients with suspected CAD. METHODS: The study group
      consisted of 1036 consecutive patients (700 men; 67.6% ) in the mean age of
      62.1+/-9.7 (25-85) years admitted to coronary angiography. Simultaneously renal
      angiography was performed in all patients. RESULTS: Stenosis > or = 50% in at
      least one main branch of coronary artery was found in 633 (66.1%) patients. The
      proportion of patients with one, two or three vessel CAD was respectively 291
      (46%), 169 (26%) and 173 (27.3%). Non-significant coronary lesions <50% were
      found in 108 (10.4%) patients, whereas in 295 (28.5%) patients no angiographic
      evidence of CAD was documented. In the whole group of patients RAS was found in
      339 (32.7%) of patients - 124 (12%) had bilateral lesions. RAS prevalence in
      patients with CAD was 38.3% (284/741) and its frequency increased with severity
      of CAD: from 25% (27/108) in patients with insignificant coronary lesions up to
      36.4% (106/291), 40.2% (68/169) and 48% (83/173) in 1, 2, and 3-vessel disease,
      respectively (p <0.001). RAS prevalence in patients with normal coronary arteries
      was 18.6% (55/295). RAS <30% was detected in 194 (18,7%) patients; RAS between 30
      49% in 81 patients (8.7%); RAS 50-69% in 38 patients (3.7%) and RAS > or = 70% in
      the remaining 26 patients (2.5%). RAS > or = 50% was noted in 8 (2.7%) patients
      without coronary lesions; in 5 (4.6%) with insignificant coronary artery
      atherosclerosis and 51 (8%) with coronary artery stenosis >50% (p=0.0008).
      Stepwise regression analysis identified 4 independent predictors of RAS > or =
      50%: CAD severity (p=0.014), serum creatinine concentration (p <0.001), cigarette
      smoking (p=0.02) and stenosis of aortic arch branches (p <0.001). CONCLUSIONS:
      RAS is a frequent finding in patients with suspected CAD. CAD severity, number of
      involved aortic arch arteries, cigarette smoking and serum creatinine are
      independent RAS predictors.

PMID- 18803138
TI  - [An old looped lead removal, complicated by its knotting over the active right
      ventricular lead - a case report].
AB  - We present a 59 year old patient with advanced heart failure who underwent lead
      extraction. The lead was implanted 11 years ago, and 2 years later looped
      spontaneously following its fracture. The transvenous extraction process through
      inferior vena cava was complicated by knotting of the inactive lead over the
      active ventricular lead. The patient was pacemaker-dependent. Finally, the old
      lead was successfuly explanted. The active intact lead was used to create
      resynchronisation system.

PMID- 18803139
TI  - [An old ventricular lead migration and subsequent dislodgement to the pleural
      cavity - an unusual complication of permanent cardiac pacing].
AB  - A case of a 77 year old male with a history of multiple pacemaker replacement
      procedures, a new ventricular lead implanted and an old one left in place, and
      imminent skin erosion at the site of a pacemaker pocket is presented. Clinical
      diagnosis included right- -sided heart failure, pneumonia, pleural effusion and
      suspicion of pulmonary infarction as well as endocarditis. Chest radiogram and
      computerised tomography revealed an unusual location of an old ventricular lead
      which proximal, sharp end migrated through the venous system via right ventricle
      and pericardium to the left pleural cavity.

PMID- 18803140
TI  - Lambda-like ST segment elevation in acute myocardial infarction - a new risk
      marker for ventricular fibrillation? Three case reports.
AB  - Sudden cardiac death (SCD) is responsible for almost 50% of all cardiac deaths in
      the U.S. The most common underlying cause of SCD is coronary artery disease,
      especially acute myocardial infarction (AMI). There are no publications
      concerning the shape of ST segment elevation in AMI and the risk of ventricular
      fibrilation (VF) or SCD. We present three cases with AMI and atypical ST segment
      elevation - 'lambda-wave-like' pattern, complicated with episodes of VF. This ECG
      pattern resembles the ST segment elevation shape in the type 1C Brugada syndrome.
      The 'lambda-like' ST segment elevation in AMI may identify patients with
      increased risk of VF or SCD.

PMID- 18803141
TI  - [Constrictive pericarditis in the course of rheumatoid arthritis].
AB  - We describe a case of a patient with advanced heart failure. On the basis of
      clinical status, echocardiography and the results of magnetic resonance,
      constrictive pericarditis was diagnosed. The seropositive rheumatoid arthritis
      was the cause of the constriction. Constrictive pericarditis should be considered
      in differential diagnosis in patients with rheumatoid arthritis and heart
      failure.

PMID- 18803142
TI  - [Massive pulmonary embolism treated with a reduced dose of alteplase in a patient
      with acute renal failure].
AB  - There are some doubts whether in a severe renal failure the dose of alteplase
      should not be modified, especially when its plasma clearance may be decreased by
      liver ischemia. The authors present a case of a 67-year old woman with massive
      pulmonary embolism (PE) and acute renal failure (creatinine 580 micromol/l) of a
      mixed etiology (renal calculosis with hydronephrosis and shock as PE
      presentation). Alteplase administration (10 mg bolus followed by reduced to 50 mg
      two hours infusion) resulted in hemodynamic stabilization but was complicated by
      gross subcutaneous hematomas, intensive epistaxis and hematuria, and hemoglobin
      decrease which required blood transfusions.

PMID- 18803143
TI  - [The consequences of acute pulmonary embolism].

PMID- 18803144
TI  - [Difficulties in echocardiographic monitoring of trastuzumab therapy in breast
      cancer patients: case report and review of recommendations].

PMID- 18803145
TI  - [Are ECG changes in pulmonary artery embolism due to right ventricular
      ischaemia?].

PMID- 18803146
TI  - [Large myxoma of the left atrium presenting as systemic inflammatory syndrome - a
      case report].

PMID- 18803147
TI  - [Right coronary artery dissection during angiography in a patient with acute
      coronary syndrome].

PMID- 18803148
TI  - [A long RP tachycardia - an electrophysiological puzzle].
AB  - A case of a 30-year-old male with paroxysmal long RP tachycardia is presented.
      During electrophysiological study the clinical arrhythmia (atypical
      atrioventricular nodal reentrant tachycardia - AVNRT) was misdiagnosed as ectopic
      left atrial tachycardia due to ventricle-atrium-atrium-ventricle (VAAV) response
      after entrainment, eccentric atrial activation sequence and easiness in achieving
      atrio-ventricular dissociation with ventricular pacing during the tachycardia.
      Reassessment of the VAAV response lead to recognition of pseudo-VAAV response
      often seen in atypical, fast-slow AVNRT. Subsequent ablation of the slow pathway
      at standard site in the triangle of Koch was successful in eliminating the
      tachycardia.

PMID- 18803149
TI  - Cardiac rehabilitation in the United States: from evidence to application.

PMID- 18803150
TI  - Reverse end-to-side neurotization in a regenerating nerve.
AB  - Bypass grafting around a neuroma-in-continuity entails coapting a nerve graft
      above and below the injured segment using two sequential end-to-side repairs. The
      proximal repair is analogous to what has been classically described as an end-to
      side repair; the axons from the intact nerve sprout into the end of a recipient
      nerve and travel distally. At the distal connection, however, axons in the graft
      must enter the side of the intact nerve and find their way to appropriate end
      organs. This process has not been well investigated. To examine this, a reverse
      end-to-side repair, suturing the distal end of the peroneal nerve to the side of
      a transected and repaired tibial nerve, was performed in 20 rats. A primary end
      to-end repair of the tibial nerve was performed in 10 additional rats. Twelve
      weeks later, contraction forces of the gastrocnemius muscle were measured
      following proximal stimulation. Measurements were repeated following elimination
      of potential axonal pathways to identify which axons (peroneal or tibial) had
      achieved greater reinnervation. The results indicated that both groups of axons
      had achieved significant reinnervation. This study supports the idea that a
      reverse end-to-side repair can result in axonal invasion of an intact but
      regenerating nerve and achieve functional recovery.

PMID- 18803151
TI  - [The place of sonography in the diagnostic work-up of haemangiomas and vascular
      malformations].
AB  - While in one of three children a vascular birthmark may be a transient finding,
      in one of hundred children a persisting vascular soft tissue malformation is
      seen, which warrants further diagnostic work-up. An exact diagnosis is crucial
      for assessment of the prognosis and future evolution of the lesion as well as for
      efficient treatment. In experienced hands, sonography can be used as a first line
      modality since, together with color Doppler and spectral wave analysis, it allows
      for a simple but exact differentiation of these lesions in many cases. In
      addition sonography is well tolerated especially in children. Besides its
      diagnostic impact, sonography is also well suited for the guidance of
      interventional treatment, such as percutaneous sclerotherapy. In this Original
      article, the strengths and weaknesses of sonography are discussed in detail.

PMID- 18803152
TI  - [The social and familial dimension: experiences of caregivers and people with
      multiple sclerosis. The GEDMA study].
AB  - INTRODUCTION: Comparing the perceptions of multiple sclerosis (MS) patients and
      caregivers with regard to the same social and familial issues, as well as delving
      deeper into the factors that determine the quality of life of these patients and
      their relatives by using a qualitative methodology, can help us to complete the
      information on the same topic that has already been collected using scales and
      quantitative protocols. AIM: To analyse how a group of people with MS and their
      caregivers perceive the disease by examining the way they talk about their
      experience with it. SUBJECTS AND METHODS: A qualitative methodology was used;
      more particularly, data were obtained by holding six discussion groups made up of
      patients and caregivers, who were members of MS patient associations. RESULTS:
      People with MS reported the social stigma attached to suffering from the disease.
      Many of the caregivers thought that patients with MS did not accept the disease
      and felt that over-protection was of little help in coming to terms with the
      disease and should therefore be avoided. Remunerated work was described by
      caregivers as a factor that, at the same time, generated and protected the
      burden. CONCLUSIONS: The social stigma, the lack of work and coming to terms with
      MS were the greatest issues for the patient, while support from the family
      network, the relationship that should be established with the patient, the impact
      of MS on children and the role played by remunerated work were the main
      dimensions of the disease for the caregiver.

PMID- 18803153
TI  - [Childhood epilepsy status in a university hospital: a descriptive study].
AB  - INTRODUCTION: Epileptic status (ES) is a medical emergency with a high rate of
      morbidity and mortality. AIM. To produce a retrospective description of the ES
      that are seen in the paediatric population attended in our centre. PATIENTS AND
      METHODS: We surveyed the records of 41 patients who presented ES and were
      controlled in the child neurology department between December 1999 and June 2007.
      Depending on the type of seizures, the cases were classified as either convulsive
      ES (CES) or non-convulsive ES (NCES). They were divided into categories according
      their causation using the modified Hauser classification. Newborn infants were
      excluded. RESULTS: A total of 41 patients were analysed, 25 (60%) of whom were
      males. The mean age was 32 months. Fifty-one per cent of cases were CES and 49%
      were NCES. Acute symptomatic ES (ASES) was the most frequent, especially in those
      under 2 years of age. ES recurrence was found to be 42% and ASES stood out as the
      least recurrent. The mortality rate was 2%. CONCLUSIONS: There was no difference
      in the number of cases between CES and NCES, probably due to the use of continual
      electroencephalogram monitoring in hospitalised patients with impaired
      consciousness. Hypoxic-ischaemic events were the chief cause of ASES, and
      malformations of the central nervous system prevailed in those of a remote
      aetiology. The rate of recurrence was high and in such cases patients must be
      submitted to a strict follow-up, especially those with an underlying condition.

PMID- 18803154
TI  - [Analysis of intrusive errors in a memory test as possible pre-clinical marker of
      familial Alzheimer disease, in E280A presenilin-1 mutation carrier].
AB  - INTRODUCTION: Intrusive errors in verbal memory tests could be considered as a
      preclinical marker of familial Alzheimer disease (AD). AIMS. To analyze and to
      compare the number and types of intrusive errors in the CERAD verbal memory test,
      administered to a genealogy of affected by familial AD, with E280A presenilin-1
      mutation. PATIENTS AND METHODS: Sample was constituted by 30 asymptomatic non
      carriers (ANC), 39 non-demented carriers (NDC) and 21 demented carriers (DC).
      CERAD verbal memory test was administered to the sample. Comparisons, with non
      parametric Kruskal-Wallis' analysis, were done. RESULTS: NDC participants
      presented more intrusive errors than ANC group in the first and second trials and
      in the delay recall of the memory task; also they had more intrusive errors than
      the DC patients in intrusive errors of the first trial and delay recall of the
      same task. The ANC and DC groups had significantly more intrusions only in third
      trial. CONCLUSION: Intrusive errors could be considered as a cognitive
      preclinical marker for familial AD.

PMID- 18803155
TI  - [Clinical usefulness of transcranial Doppler ultrasound imaging in the diagnosis
      of cerebral vasospasm in subarachnoid haemorrhage. A validation study].
AB  - INTRODUCTION: During the clinical course of aneurysmal subarachnoid haemorrhage,
      cerebral vasospasm is one of the most dreaded medical complications. AIM. To
      determine the usefulness of transcranial Doppler (TCD) ultrasound imaging in
      diagnosing vasospasm in patients with subarachnoid haemorrhage (SAH) who were
      attended in a Stroke Unit. PATIENTS AND METHODS: The study included 89 patients
      with SAH of a non-traumatic origin; these patients had been admitted to a Stroke
      Unit and were submitted to a contrast-enhanced neurovascular study and daily
      monitoring with TCD. Values were determined for the sensitivity, specificity,
      predictive power and overall precision of the TCD ultrasound imaging, together
      with the differences in mean flow rate and the coefficient of correlation between
      the gold standard test and the results of monitoring with TCD. RESULTS: Female
      patients under 50 years of age with favourable initial clinical degrees were
      predominant. Aneurysmal SAH was prevalent and the frequency of angiographic
      vasospasm was 40%, in the majority of cases located in the middle cerebral
      arteries. Most of the patients had mean cerebral blood flow rates of or below 120
      cm/s. The peaks of mean blood flow rate were obtained between the fourth and the
      tenth day. Overall precision, sensitivity and the predictive negative value of
      TCD were good. Specificity was excellent for flow rates below 130 cm/s, and the
      predictive positive value was low. CONCLUSIONS: Monitoring with TCD proved to be
      useful for diagnosing cerebral vasospasm in patients with a good initial clinical
      status.

PMID- 18803156
TI  - [Galantamine therapy in dementia associated with CADASIL].
AB  - INTRODUCTION: Cholinergic neuronal impairment has been suggested in cerebral
      autosomal dominant arteriopathy with subcortical infarcts and leucoencefalopathy
      (CADASIL). Cholinomimetic therapy could be useful. CASE REPORTS: Four patients
      with CADASIL and dementia were treated with the acetylcholinesterase inhibitor
      galantamine and we assessed cognitive, behavioral, functional and the caregiver
      burden aspects. Three patients showed either mild improvement or stabilization in
      the behavior and caregiver burden. CONCLUSION: Our results suggest some benefit
      from galantamine treatment and they could support the existence of a cholinergic
      deficit in CADASIL.

PMID- 18803157
TI  - [Sexual intercourse as a trigger of transient global amnesia].
AB  - INTRODUCTION: Transient global amnesia (TGA) is characterised by impairment of
      anterograde memory and, to a certain extent, retrograde memory, which is
      associated with mild temporal and spatial disorientation that is completely re
      established after a few hours. There are different hypotheses about its
      pathogenesis, including theories about a possible epileptic, migrainous or
      ischaemic foundation or its being due to venous congestion in the hippocampuses,
      although the cause remains unknown. In the same way, many precipitating factors
      have been related to this disorder, including pain, anxiety, changes in
      temperature, exercise, Valsalva manoeuvres, diagnostic testing, interventionism
      and long-distance flights. Sexual intercourse has also been related to this
      condition, although how it can exert an influence is not known and few cases have
      been reported in the literature to date. CASE REPORTS: Six patients who suffered
      from signs and symptoms of TGA that were clearly related to a sexual
      relationship, in whom both the neurological examination and the complementary
      tests that were performed were completely normal. We also gather the evidence in
      favour and against the association between intercourse and this condition.
      CONCLUSIONS: Although the pathophysiological mechanisms that link sexual
      intercourse with TGA are unknown, the relation between them appears increasingly
      more often in the literature. We draw attention to the need to take sexual
      activity into account as a possible precipitating factor in patients suffering
      from this disorder.

PMID- 18803158
TI  - [Evaluation of the motor behavior in rats with cortical ablation].
AB  - INTRODUCTION: The cortical ablation has been used as an experimental model in
      order to study the basic mechanisms of functional recovery. However, there is not
      data concerning to the injury effects on the motor and somatosensorial behavioral
      manifestations that allow us to categorize such sequels as a hemiplegic model.
      MATERIALS AND METHODS: We used 35 male Wistar rats (280-300 g) allocated in two
      groups: control (n = 17) and brain injured by cortical ablation (n = 18).
      Previously trained, basal recordings of the footprint and motor and
      somatosensorial assessment were performed in the rats before surgery. The
      behavioral tests were performed again 6 hours after surgery and the spontaneous
      ambulatory activity was also evaluated. RESULTS AND CONCLUSIONS: It was observed
      a decrease in the stride's length and an increase in the stride's angle and in
      the motor deficit, while the somatosensorial assessment and spontaneous
      ambulatory activity were not affected. These findings are discussed in function
      of the motor features of the hemiparetic sequels in humans.

PMID- 18803159
TI  - [Stereotactic biopsy versus spectroscopy in cases of gliomas with a high degree
      of malignancy. A review of the literature].
AB  - INTRODUCTION: High-grade malignant gliomas have a high mortality. Stereotactic
      biopsy is the gold standard technique to obtain diagnostic information about this
      kind of tumours but it can be dangerous. New technologies as the magnetic
      resonance spectroscopy (MRS) are an alternative option. AIM: We suggest the
      possibility of replacing stereotactic biopsy for new imaging technologies in
      patients with high-grade malignant gliomas and a very limited life expectancy due
      to tumoral irresectability, among other factors. We systematically analyze the
      literature checking the diagnostic accuracy and complications of stereotactic
      biopsy as well as of new technologies like the MRS. DEVELOPMENT: The average
      morbidity of stereotactic biopsy is 3.2% and the average mortality is 0.83%. The
      percentage of cases with a diagnosis (diagnostic yield) is 96%, but accuracy of
      that diagnosis is 79%. As regards MRS, sensitivity, specificity, positive
      predictive value (PPV) and negative predictive value (NPV) for identifying high
      grade gliomas are 89.8, 88.2, 95.3 and 79.7%, respectively. CONCLUSIONS:
      Stereotactic biopsy presents a quite high morbi-mortality with a real accuracy
      diagnostic of 75.8% after considering the diagnostic yield. With regard to MRS,
      there are very few studies about accuracy diagnostic but, however; there are many
      about sensitivity, specificity, PPV and NPV, being these last values very high.
      In spite of that, we cannot conclude that stereotactic biopsy can be substituted
      for the MRS because there are not enough studies to support this conclusion.

PMID- 18803160
TI  - [Anatomical and neurochemical bases accounting for the frequent association
      between headaches and sleep: the hypnic headache paradigm].
AB  - INTRODUCTION: The relationship between headache and sleep is complex and runs in
      two directions. Headache may be the consequence of a (primary or secondary) sleep
      disorder or its cause (in chronic tension-type headache and/or chronic migraine
      with or without painkiller abuse). It can also be related to sleep in an
      intrinsic way, as in the case of hypnic headache (which only appears during
      sleep) or other primary headaches, such as migraine and certain trigeminal
      autonomic cephalgias (which can appear during the waking state or during sleep);
      this type of headache occurs mostly during REM sleep. DEVELOPMENT: The neural
      pathways that control sleep and pain are anatomically, physiologically and
      neurochemically cross-linked. These neural systems are located in the brain stem,
      the hypothalamus and the basal brain. Such cross-links are produced on two
      different levels. On the one hand, they occur in the serotoninergic nuclei of the
      brain stem, whose activity in physiologically diminished during REM sleep and
      which are involved in antinociceptive control. On the other hand, they are also
      to be found in the hypothalamus, where serotoninergic terminals have been
      detected in the suprachiasmatic nucleus (SCN). As cells in the SCN are lost with
      age, their circadian and homeostatic functioning fails, the activity of the
      hypothalamus-pineal axis is reduced and the endogenous melatonin rhythm is
      altered. This results in a disorder affecting the control of the sleep-waking
      cycle and antinociceptive control. CONCLUSIONS: Dysfunctions in these neuronal
      networks in the brain stem (especially in the serotoninergic nuclei) or the
      hypothalamus (SCN) can account for headaches that begin in the REM phase of sleep
      and affect biologically predisposed subjects.

PMID- 18803161
TI  - [Massive infarction of the brain stem as a consequence of atherothrombotic
      occlusion of the basilar artery].

PMID- 18803163
TI  - [Sexsomnia: a new case description].

PMID- 18803164
TI  - [Psychosis, visual hallucinations and worsening renal function due to a
      gabapentine-morphine interaction].

PMID- 18803165
TI  - [Kleine-Levin syndrome. A description of a case in a teenage girl].

PMID- 18803166
TI  - [Falls in patients with neurogeriatric disorders].

PMID- 18803167
TI  - [Cryptococcosis of the central nervous system in immunocompetent patients].

PMID- 18803169
TI  - Phytotoxicity of GF-120 NF Naturalyte fruit fly bait carrier on sweet cherry
      (Prunus avium L.) foliage.
AB  - BACKGROUND: Six sweet cherry (Prunus avium L.) cultivars were tested with GF-120
      with spinosad (0.2 g L(-1) spinosad bait) or without it (blank bait) to
      understand leaf phytotoxicity observed in the field. RESULTS: Spinosad bait and
      blank bait did not differ significantly with respect to damage observed. Leaf
      damage was found almost exclusively at the abaxial (lower) surfaces with the
      doses (0, 17, 20, 25 or 40%) and cultivars tested. The effects of the blank bait
      on abaxial surfaces increased from 24 to 168 h, and with dose, in terms of the
      proportion of droplets (0.00, 0.42, 0.52, 0.75 or 0.94) and area (0.0, 18.7,
      23.5, 40.5 or 91.6 mm) burned. In addition, chlorophyll was reduced with
      increasing dose on abaxial surfaces (SPAD = 44.6, 36.1, 34.1, 31.0, 21.5), but
      not on adaxial (upper) surfaces (SPAD = 44.6, 44.2, 44.0, 44.8, 44.4). The
      chlorophyll level in undamaged leaves (adaxial surfaces) differed by cultivar.
      Cherry leaves were less damaged by a 20% bait application in June (0.26) than in
      July (0.46) and August (0.50). Incidental insect leaf feeding at bait locations
      occurred at a low rate and was highest on abaxial bait surfaces. CONCLUSIONS:
      Applying GF-120 to the adaxial leaf surface, or at doses of <or=20%, will
      minimize leaf phytotoxicity.

PMID- 18803170
TI  - Addition of risperidone to sertraline improves sertraline-resistant refractory
      depression without influencing plasma concentrations of sertraline and
      desmethylsertraline.
AB  - In the present study, we examined the efficacy of risperidone addition on
      sertraline-resistant depressed patients and the effects of risperidone on the
      metabolism of sertraline. Ten patients (M/F: 4/6, age: 54 +/- 10 years) met the
      DSM-IV criteria for major depressive disorder enrolled the study. Hamilton Dating
      Scale for Depression (HAM-D) scores (mean +/- SD) in all 10 patients
      significantly decreased from 19 +/- 4 (before risperidone addition) to 11 +/- 3
      (4 weeks after risperidone addition). Plasma levels of sertraline and
      desmethylsertraline did not change after risperidone addition. Serum BDNF levels
      in responders to risperidone addition were changed from 8.1 +/- 2.7 ng/ml (before
      risperidone addition) to 11.5 +/- 0.9 ng/ml (4 weeks after risperidone addition);
      in contrast, those in nonresponders changed from 7.8 +/- 2.2 ng/ml (before
      risperidone addition) to 7.9 +/- 2.4 ng/ml (4 weeks after risperidone addition).
      These results suggest that the addition of risperidone to sertraline is effective
      and well tolerated for sertraline-resistant depressive patients, which is
      accompanied with the increase in serum BDNF levels in responders to the
      risperidone addition, and the addition of risperidone to sertraline does not seem
      to influence sertraline metabolism.

PMID- 18803171
TI  - Aromatic amino acids in weight-recovered females with anorexia nervosa.
AB  - OBJECTIVE: Most previous studies investigating amino acid levels in anorexia
      nervosa (AN) have focused on acutely underweight patients. The present study
      assessed the availability of aromatic amino acids in the plasma of weight
      recovered outpatients with AN (recAN) in comparison to acutely underweight AN
      patients (acAN) and healthy control woman (HCW). METHOD: Plasma tryptophan (TRP),
      tyrosine (TYR), and phenylalanine (PHEN) as well as leptin concentration were
      determined in 32 recAN, 32 acAN, and 32 HCW. RESULTS: Both recAN and acAN
      patients showed significantly lower levels of TRP and PHEN when compared to HCW.
      TYR was reduced in acAN patients only. DISCUSSION: Normal weight and normal
      leptin levels but lower availability of TRP and PHEN in recAN patients might
      indicate that outside a tightly controlled setting these patients still engage in
      abnormal eating patterns. Reduced peripheral availability of these precursor
      amino acids could impact on 5-HT and catecholamine functioning in the brain.

PMID- 18803172
TI  - The development of hunger and fullness during a laboratory meal in patients with
      binge eating disorder.
AB  - OBJECTIVE: This study aimed to test the hypothesis that, compared to similarly
      obese participants without BED, individuals with BED have a disturbance in the
      development of fullness and reduction of hunger during the course of a standard
      meal of large size. METHOD: Thirteen patients with BED and 14 obese control
      participants consumed 975 g of a milkshake. Participants received no information
      about how much they had eaten or how much of the meal remained to be consumed.
      Participants were interrupted after every 75 g consumed to rate hunger and
      fullness. RESULTS: Final fullness ratings were higher in patients with BED, but
      there were no differences in mean duration or mean rate of eating, or in changes
      in subjective ratings of hunger and fullness per gram of food. DISCUSSION: The
      current study reports the surprising finding of no difference in reports of
      hunger and fullness between patients with BED and obese controls.

PMID- 18803173
TI  - "Ice" use and eating disorders: a report of three cases.
AB  - OBJECTIVE: To describe the use of crystal methamphetamine hydrochloride "ice," a
      powerful, synthetic stimulant drug associated with rapid weight loss. METHOD: We
      report the first three cases of young women "ice" users requiring admission to a
      specialized eating disorders unit. RESULTS: Case one had no prior history of an
      eating disorder and became emaciated following regular use of "ice"; she regarded
      weight gain positively. Case 2 had polysubstance abuse since early adolescence
      and commenced binge eating and vomiting in response to weight gain when not using
      "ice"; she learned to maintain her weight without weight losing behaviors. Case 3
      developed anorexia nervosa in early adolescence, required numerous inpatient
      admissions and commenced using stimulant drugs for weight loss in her late teens;
      she discharged prematurely. All patients had features of personality disorder on
      interview and drug abuse had impaired their work and social adjustment.
      DISCUSSION: "Ice" use may be associated with the onset of disordered eating or
      used as an efficient weight losing behavior in an established eating disorder.

PMID- 18803174
TI  - Correlated responses to neonicotinoid insecticides in clones of the peach-potato
      aphid, Myzus persicae (Hemiptera: Aphididae).
AB  - BACKGROUND: Although there are still no confirmed reports of strong resistance to
      neonicotinoid insecticides in aphids, the peach-potato aphid (Myzus persicae
      Sulzer) shows variation in response, with some clones exhibiting up to tenfold
      resistance to imidacloprid. Five clones varying in response to imidacloprid were
      tested with four other neonicotinoid molecules to investigate the extent of cross
      resistance. RESULTS: All four compounds-thiamethoxam, thiacloprid, clothianidin
      and dinotefuran-were cross-resisted, with ED(50) values ranked in the same order
      as for imidacloprid. Resistance factors ranged up to 11 for imidacloprid, 18 for
      thiamethoxam, 13 for thiacloprid, 100 for clothianidin and 6 for dinotefuran.
      CONCLUSION: This variation in response does not appear to be sufficient to
      compromise the field performance of neonicotinoids aimed at controlling aphids.
      However, it highlights the need for careful vigilance and stewardship in all M.
      persicae populations, and a need to consider neonicotinoids as a single cross
      resisted group for management purposes.

PMID- 18803175
TI  - Neonicotinoid resistance in rice brown planthopper, Nilaparvata lugens.
AB  - BACKGROUND: Rice brown planthopper, Nilaparvata lugens Stal, is a primary insect
      pest of cultivated rice, and effective control is essential for economical crop
      production. Resistance to neonicotinoid insecticides, in particular imidacloprid,
      has been reported as an increasing constraint in recent years. In order to
      investigate the extent of resistance, 24 samples of N. lugens were collected from
      China, India, Indonesia, Malaysia, Thailand and Vietnam during 2005 and 2006.
      Their responses to two diagnostic doses of imidacloprid (corresponding
      approximately to the LC(95) and 5 x LC(95) of a susceptible strain) were
      examined. RESULTS: Ten of the 12 samples collected during 2005 were found to be
      susceptible to imidacloprid, but two late-season samples from India showed
      reduced mortality at both diagnostic doses. All 13 strains collected in 2006
      showed reduced mortality at both doses when compared with the susceptible strain.
      Dose-response lines showed resistance in one of the most resistant field strains
      to be approximately 100-fold compared with the susceptible standard. CONCLUSION:
      The data demonstrate the development and spread of neonicotinoid resistance in N.
      lugens in Asia and support reports of reduced field efficacy of imidacloprid.

PMID- 18803176
TI  - Simple synthesis of multiwalled carbon nanotubes from natural resources.

PMID- 18803177
TI  - Method for determination of total cysteamine in human plasma by high performance
      capillary electrophoresis with acetonitrile stacking.
AB  - An analytical procedure enabling routine analysis of human plasma for total
      cysteamine (CASH) has been developed and validated. The method includes reduction
      of CASH disulfides to thiol with tri-n-butylphosphine, derivatization of the
      thiol with 2-chloro-1-methylquinolinium tetrafluoroborate, separation of CASH 2-S
      quinolinium derivate from those of plasma endo- and exogenous thiol derivatives
      by capillary zone electrophoresis based on acetonitrile stacking and quantitation
      with the use of ultraviolet detection. A large volume of sample is injected to
      achieve analyte concentration directly on the capillary, according to the
      transient pseudo-isotachophoresis principle, before the separation step takes
      place. Method performance characteristics, for example recovery, calibration,
      precision, limit of detection and limit of quantitation are presented. The
      procedure was applied to analysis of plasma samples donated by apparently healthy
      volunteers spiked with known amounts of cystamine standard solution.

PMID- 18803178
TI  - Determination of flurbiprofen enantiomers in plasma using a single-isomer amino
      cyclodextrin derivative in nonaqueous capillary electrophoresis.
AB  - A nonaqueous capillary electrophoresis (NACE) assay was developed for the
      separation and determination of flurbiprofen enantiomers in plasma samples using
      6-monodeoxy-6-mono(3-hydroxy)propylamino-beta-cyclodextrin as chiral selector.
      The nonaqueous background electrolyte was made up of 40 mM ammonium acetate in
      methanol (MeOH), and flufenamic acid was employed as internal standard. Solid
      phase extraction was used for sample cleanup prior to the NACE separation. The
      NACE method reproducibility was optimized by evaluating different capillary
      washing sequences between runs. After having tested various conditions,
      trifluoroacetic acid (1 M) in MeOH was finally selected. Concerning the solid
      phase extraction procedure, good and reproducible analyte recoveries were
      obtained using MeOH for protein denaturation and a polymeric phase combining
      hydrophobic interactions with anion exchange properties (Oasis) MAX) was selected
      as extraction sorbent. The method selectivity was not only demonstrated toward a
      blank plasma sample but also toward other non-steroidal anti-inflammatory drugs.
      The method was then successfully validated with respect to response function,
      trueness, precision, accuracy, linearity and limit of quantification.

PMID- 18803179
TI  - Sensitive analysis of donepezil in plasma by capillary electrophoresis combining
      on-column field-amplified sample stacking and its application in Alzheimer's
      disease.
AB  - Field-amplified sample stacking (FASS) in capillary electrophoresis (CE) was used
      to determine the concentration of donepezil, an acetylcholinesterase inhibitor,
      in human plasma. A sample pretreatment by liquid-liquid extraction with
      isopropanol/n-hexane (v/v 3:97) and subsequent quantification by FASS-CE was
      used. Before sample loading, a water plug (0.5 psi, 6 s) was injected to permit
      FASS. Electrokinetic injection (7 kV, 90 s) was used to introduce sample cations.
      The separation condition for donepezil was performed in electrolyte solutions
      containing Tris buffer (60 mM, pH 4.0) with sodium octanesulfonate 40 mM and
      0.01% polyvinyl alcohol as a dynamic coating to reduce analytes' interaction with
      capillary wall. The separation was performed at 28 kV and detected at 200 nm.
      Using atenolol as an internal standard, the linear ranges of the method for the
      determination of donepezil in human plasma were over a range of 1-50 ng/mL. The
      limit of detection was 0.1 ng/mL (S/N=3, sampling 90 s at 7 kV). One female
      volunteer (54 years old) was orally administered a single dose of 10 mg donepezil
      (Aricept, Eisai), and blood samples were drawn over a 60 h period for
      pharmacokinetic study. The method was also applied successfully to monitor
      donepezil in sixteen Alzheimer's disease patients' plasmas.

PMID- 18803180
TI  - A simple and rapid CZE method for the analysis of mycophenolic acid and its
      phenol glucuronide metabolite in human serum.
AB  - A simple and rapid capillary electrophoretic method was developed for
      simultaneous determination of mycophenolic acid and its metabolite, phenol
      glucuronide, in human serum. The sample preparation in the proposed method
      required only the precipitation by acetonitrile. Separation was performed by
      capillary zone electrophoresis using 75 mM phosphate buffer (pH 7.5) as running
      buffer, an applied voltage of 10 kV, and UV detection at 217 nm. Each serum
      sample analysis was completed within 15 min. The optimized method demonstrated
      good performance concerning specificity, linearity (r>0.9955), accuracy (95.9
      113%), precision (<6.4%) and enough sensitivity for therapeutic drug monitoring.
      This method was successfully applied to measurements of mycophenolic acid and
      mycophenolic acid glucuronide in renal transplant patient samples and was a
      useful alternative to high-performance liquid chromatography-based methods.

PMID- 18803181
TI  - On-line stacking capillary electrophoresis for analysis of methotrexate and its
      eight metabolites in whole blood.
AB  - Therapeutic drug monitoring of methotrexate (MTX) and its metabolites is
      significant for the evaluation of treatment response of acute lymphoblastic
      leukemia and the prevention of adverse effects. Those eight metabolites including
      7-hydroxymethotrexate, MTX-polyglutamate derivatives (MTX-(Glu)(n), n=2-7), and
      2,4-diamino-N(10)-methylpteroic acid, especially the MTX-(Glu)(n), only exist in
      blood cells and also present antifolate effects. Therefore, whole blood analysis
      has importance in clinical therapy. This study combined solid-phase extraction
      and on-line stacking capillary electrophoresis to examine the levels of MTX and
      its eight metabolites in whole blood. A higher conductivity buffer (HCB) was used
      to accumulate large amount of samples into a narrow zone, which resulted in
      effective stacking and sharp peaks. A fused-silica capillary was filled with
      phosphate buffer (80 mM, pH 2.5) containing 15% v/v tetrahydrofuran and 100 mM
      sodium dodecyl sulfate. Then HCB (100 mM phosphate, pH 2.5; 1 psi, 60 s) was
      injected for accumulating large volume of analytes (1 psi, 200 s). Owing to the
      pH difference between sample zone and HCB, dynamic pH junction was generated for
      focusing. Meanwhile, sweeping made further stacking by using sodium dodecyl
      sulfate in phosphate buffer. The limits of detection (S/N=3) were 0.1 microM for
      MTX, 0.2 microM for 7-hydroxymethotrexate and 2,4-diamino-N(10)-methylpteroic
      acid, 0.3 microM for MTX-(Glu)(n=2--5), and 0.5 microM for MTX-(Glu)(n=6--7).
      During validation, this method showed good linearity (r> / =0.9914) and
      reproducibility (relative standard deviation and relative error, both less than
      13%). The applications were performed to monitor blood MTX and its metabolites in
      acute lymphoblastic leukemia patients. The blood concentrations could provide
      some information related to therapeutic response and adverse effects.

PMID- 18803182
TI  - A method for rapidly predicting drug tissue distribution using surfactant vesicle
      electrokinetic chromatography.
AB  - Lung tissue distribution of an inhaled drug is important for its potency in the
      airways and with minimum systemic effects within its dose range. As the lung has
      the smallest diffusion distance of all the organs in the body and negligible
      diffusion delays, the characteristics of drug distribution in the lung will
      mainly depend on drug binding to both tissue and plasma protein. This research
      aims to develop and evaluate surfactant vesicle electrokinetic chromatography
      (SEKC) methods for high throughput profile prediction of tissue distribution for
      inhaled drugs. Several electrokinetic chromatography methods reported in the
      literature, as well as immobilised artificial membrane chromatography, were
      compared and evaluated in respect to chromatographic characteristics and
      statistical correlations. Among these methods, the docusate sodium salt (AOT)
      SEKC system showed good reproducibility, short run time, and the highest
      selectivity for alkylphenone test compounds. It also showed a significant
      statistical correlation between the retention of inhaled drugs and their in vivo
      volume of distribution at steady-state (V(ss)) in whole human body neglecting the
      plasma protein-binding differences. Stronger correlations were observed between
      the AOT SEKC retention of a series of basic drugs and their rat lung tissue-to
      plasma water partitioning coefficient (K(pu)), which is affected only by drug
      binding to the tissue constituent. Further, on comparing correlations between AOT
      SEKC retention and K(pu) at various rat tissues, it was observed that the
      strongest correlation was with lung tissue distribution, while the weakest was
      with brain tissue distribution.

PMID- 18803183
TI  - A highly sensitive CE-UV method with dynamic coating of silica-fused capillaries
      for monitoring of nucleotide pyrophosphatase/phosphodiesterase reactions.
AB  - A new highly sensitive capillary electrophoresis (CE) method applying dynamic
      coating and on-line stacking for the monitoring of nucleotide
      pyrophosphatases/phosphodiesterases (NPPs) and the screening of inhibitors was
      developed. NPP1 and NPP3 are membrane glycoproteins that catalyze the hydrolysis
      nucleotides, e.g. convert adenosine 5'-triphosphate to adenosine 5'-monophosphate
      (AMP) and pyrophosphate. Enzymatic reactions were performed and directly
      subjected to CE analysis. Since the enzymatic activity was low, standard methods
      were insufficient. The detection of nanomolar AMP and other nucleotides could be
      achieved by field-enhanced sample injection and the addition of polybrene to the
      running buffer. The polycationic polymer caused a dynamic coating of the silica
      fused capillary, resulting in a reversed electroosmotic flow. The nucleotides
      migrated in the direction of the electroosmotic flow, whereas the positively
      charged polybrene molecules moved in the opposite direction, resulting in a
      narrow sample zone over a long injection time. Using this on-line sensitivity
      enhancement technique, a more than 70-fold enrichment was achieved for AMP (limit
      of detection, 46 nM) along with a short migration time (5 min) without
      compromising separation efficiency and peak shape. The optimized CE conditions
      were as follows: fused-silica capillary (30 cm effective lengthx75 mum),
      electrokinetic injection for 60 s, 50 mM phosphate buffer pH 6.5, 0.002%
      polybrene, constant current of -60 microA, UV detection at 210 nm, uridine 5'
      monophosphate as the internal standard. The new method was used to study enzyme
      kinetics and inhibitors. It opens an easy way to determine the activities of
      slowly metabolizing enzymes such as NPPs, which are of considerable interest as
      novel drug targets.

PMID- 18803184
TI  - Kinetic study of cytochrome P450 by capillary electrophoretically mediated
      microanalysis.
AB  - An electrophoretically mediated microanalysis method for the determination of
      CYP3A4 activity using testosterone and nifedipine as substrates was developed.
      Initially, the enzymatic reaction was performed off-line and the samples were
      subsequently injected into the capillary by pressure. The CYP3A4 activity was
      determined by quantitation of the reactant cofactor, NADPH. To further optimize,
      speed-up and miniaturize the enzyme assay, the enzymatic reaction was performed
      directly in the capillary, prior to separation and quantitation of the product
      cofactor, NADP, employing the plug-plug mode of electrophoretically mediated
      microanalysis. An amplification step was introduced by means of an on-capillary
      incubation of 15 min, in order to accumulate enough reaction product to detect
      spectrophotometrically at 260 nm. This setup resulted in a fully automated assay,
      which can be carried out in less than 35 min. Using the Lineweaver-Burk equation,
      the Michaelis constants (K(m)) for the oxidation of testosterone and nifedipine
      by CYP3A4 were calculated to be 58.6+/-8.3 and 19.1+/-2.4 microM, respectively,
      which are consistent with off-line assay and previously reported values.

PMID- 18803185
TI  - Determination of pharmaceuticals classified as emerging pollutants using
      capillary electrophoresis with capacitively coupled contactless conductivity
      detection.
AB  - A study on the simultaneous separation of 13 pharmaceutical products by capillary
      electrophoresis with capacitively coupled contactless conductivity detection was
      presented. The parameters of the background electrolyte, such as pH, organic
      additives as well as types and concentrations of cyclodextrins (CD) were studied.
      The optimal separation conditions were achieved with a background electrolyte
      consisting of 9 mM Tris/5 mM lactic acid at pH 8.0, containing 5% n-propanol,
      0.025% gamma-CD, 0.075% hydroxyl-beta-CD and 0.15% dimethyl-beta-CD. Limits of
      detections ranged from 61 to 1676 microg/L (S/N=3) and the relative standard
      deviations for migration time and peak area were below 2 and 6%, respectively.
      This demonstrated the potential of the capillary electrophoresis-capacitively
      coupled contactless conductivity detection method for biomedical and
      environmental analysis, as shown in the determination of pharmaceuticals
      identified as emerging pollutants in water samples.

PMID- 18803188
TI  - Three polymorphic forms of the co-crystal 4,4'-bipyridine/pimelic acid and their
      structural, thermal, and spectroscopic characterization.
AB  - Three crystal forms of the co-crystal 4,4'-bipy/pimelic acid (bipy: bipyridine),
      [NH(4)C(5)-C(5)H(4)N][HOOC(CH(2))(5)COOH], have been prepared and their
      relationship investigated by single-crystal X-ray diffraction, variable
      temperature X-ray powder diffraction, differential scanning calorimetry and solid
      state NMR spectroscopy. Both X-ray and NMR spectroscopic results indicate that no
      proton transfer takes place, that is, the three crystal forms are true co
      crystals of neutral molecules. Forms I and II both convert into Form III at high
      temperature, Forms II and III being the thermodynamically stable forms at room
      and high temperature, respectively.

PMID- 18803189
TI  - Ruthenium complexes of substituted hydrazine: new solution- and solid-state
      binding modes.
AB  - The methylhydrazine complex [Ru(NH(2)NHMe)(PyP)(2)]Cl(BPh(4)) (PyP=1-[2
      (diphenylphosphino)ethyl]pyrazole) was synthesised by addition of methylhydrazine
      to the bimetallic complex [Ru(mu-Cl)(PyP)(2)](2)(BPh(4))(2). The methylhydrazine
      ligand of the ruthenium complex has two different binding modes: side-on (eta(2)
      ) when the complex is in the solid state and end-on (eta(1)-) when the complex is
      in solution. The solid-state structure of [Ru(PyP)(2)(NH(2)NHMe)]Cl(BPh(4)) was
      determined by X-ray crystallography. 2D NMR spectroscopic experiments with (15)N
      at natural abundance confirmed that in solution the methylhydrazine is bound to
      the metal centre by only the -NH(2) group and the ruthenium complex retains an
      octahedral conformation. Hydrazine complexes [RuCl(PyP)(2)(eta(1)
      NH(2)NRR')]OSO(2)CF(3) (in which R=H, R'=Ph, R=R'=Me and NRR'=NC(5)H(10)) were
      formed in situ by the addition of phenylhydrazine, 1,1-dimethylhydrazine and N
      aminopiperidine, respectively, to a solution of the bimetallic complex [Ru(mu
      Cl)(PyP)(2)](2)(OSO(2)CF(3))(2) in dichloromethane. These substituted hydrazine
      complexes of ruthenium were shown to exist in an equilibrium mixture with the
      bimetallic starting material.

PMID- 18803190
TI  - New templating strategies with salen scaffolds (Salen=N,N'
      bis(salicylidene)ethylenediamine dianion).
AB  - Templated approaches towards selective organic synthesis is a common feature in
      nature in which nucleic acid templated synthesis plays a crucial role in various
      fundamental biological processes. The key feature that allows control over the
      amazing selectivity found in natural processes is evidently the effective
      molarity of the reaction partners that is mediated by the macromolecular
      templation event. An ongoing challenge within many chemical sciences is to
      exploit similar templating principles and make use of synthetic systems that are
      designed for specific chemical conversions. Here, we describe the recent
      developments that involve (metallo)salen scaffolds that are used for diverse
      templating events (salen=N,N'-bis(salicylidene)ethylenediamine dianion).

PMID- 18803191
TI  - Resin-bound aminofluorescein for C-terminal labeling of peptides: high-affinity
      polarization probes binding to polyproline-specific GYF domains.
AB  - A polymer support for the solid-phase synthesis of C-terminally labeled
      carboxylic acids has been developed. Fluorophore-labeled peptides were
      constructed directly on the amino group of resin-bound aminofluorescein. Fmoc
      protected aminofluorescein was coupled onto tritylpolystyrene, and the free
      phenolic hydroxyl positions of the fluorescein were blocked with suitable
      protecting groups. The mode of attachment was analyzed and found to be selective
      for the phenoxy ether linkage. The conditions for peptide synthesis on the
      labeling resin were investigated, and a small library of C-terminally labeled
      peptides was prepared. The fluorescence quantum yields of C-terminally labeled
      peptides were determined and indicated the suitability of the compounds for
      imaging and binding experiments. The obtained peptides were therefore
      investigated as fluorescence polarization probes. Two different proline-rich
      binding domains of the GYF family-CD2BP2 and PERQ2-were targeted by peptides
      labeled either C- or N-terminally. Reversible binding constants were determined
      by fluorescence polarization measurements and were verified by competition
      experiments with the corresponding unlabeled peptide. As a second control, the
      binding constants were measured by NMR titration experiments, recording the HSQC
      NMR spectra of (15)N-labeled proteins in the presence of the peptide polarization
      probes. Ligands with higher affinities than all others known previously were
      identified for both GYF domains. The competition assay with the developed
      fluorescent probe has a high statistical reliability and can thus be used for
      screening of GYF domain inhibitors.

PMID- 18803193
TI  - Structural evolution of self-assembled alkanephosphate monolayers on TiO2.

PMID- 18803192
TI  - Amyloid fibrillar meshwork formation of iron-induced oligomeric species of
      Abeta40 with phthalocyanine tetrasulfonate and its toxic consequences.

PMID- 18803195
TI  - Functionalized coordination space in metal-organic frameworks.

PMID- 18803194
TI  - Phosphorescent thymidine triphosphate sensor based on a donor-acceptor ensemble
      system using intermolecular energy transfer.
AB  - An ensemble sensor system that exhibited selective luminescence enhancement upon
      binding to thymidine 5'-triphosphate (TTP) in HEPES buffer over other nucleotides
      was developed. The ensemble system consisted of an energy acceptor (FIrpic
      bis(Zn2+-dipicolylamine conjugate, FIrpic=bis[(4,6-difluorophenyl)-pyridinato
      N,C2+]picolinate) derivative) and an energy donor (mCP-Zn2+-cyclen, mCP=N,N'
      dicarbazolyl-3,5-benzene). Among the nucleotides, the selective recognition and
      luminescence enhancement for TTP was achieved by the strong binding of the
      thymine unit to Zn2+-cyclen (cyclen=1,4,7,10-tetraazacyclododecane) and
      intermolecular energy transfer between the mCP and FIrpic moieties.

PMID- 18803196
TI  - Aerobic oxidation of hydroquinone derivatives catalyzed by polymer-incarcerated
      platinum catalyst.

PMID- 18803198
TI  - Hydrogenation of quinolines using a recyclable phosphine-free chiral cationic
      ruthenium catalyst: enhancement of catalyst stability and selectivity in an ionic
      liquid.

PMID- 18803197
TI  - Substituted 1,3,5-triazaadamantanes: biocompatible and degradable building
      blocks.

PMID- 18803199
TI  - PO4(3-)-mediated polyoxometalate supercluster assembly.

PMID- 18803200
TI  - Polytriphenylene dendrimers: a unique design for blue-light-emitting materials.

PMID- 18803201
TI  - Towards the ultimate size limit of the memory effect in spin-crossover solids.

PMID- 18803202
TI  - The extended view on the empty C2(3)-C82 fullerene: isolation, spectroscopic,
      electrochemical, and spectroelectrochemical characterization and DFT
      calculations.
AB  - An extended study of the spectroscopic and redox properties of the C(82)
      fullerene is presented. Among the nine isolated-pentagon-rule (IPR) isomers of
      the C(82) fullerene the C(82)(3) isomer with C(2) symmetry is the only stable,
      empty fullerene structure formed in the arc burning process that can be isolated
      in an isomerically pure form. Here, its formation and isolation are described and
      its structure is confirmed by experimental spectroscopic studies as well as time
      dependent DFT calculations. The electrochemistry of the C(82)(3) isomer is
      studied in detail by cyclic voltammetry and spectroelectrochemistry. The anionic
      species of C(82) with the charge ranging from C(82) (-) to C(82) (4-) were
      successively generated in o-dichlorobenzene solution at room temperature and
      characterized by in situ ESR and visible/near-infrared (Vis/NIR) spectroscopy.
      The data give new insights into the charged states of the C(82)(3) fullerene.

PMID- 18803203
TI  - Understanding the two-step spin-transition phenomenon in Iron(II) 1D chain
      materials.
AB  - Three analogous one dimensional (1D) polymeric iron(II) spin crossover (SCO)
      materials containing the new ligand 4,6-bis(2',2''-pyridyl)pyrazine (bdpp) have
      been comprehensively characterised magnetically (thermal and light-induced) and
      structurally. Within this series are two polymorphs of the formula
      [Fe(NCS)(2)(bdpp)], 1 and 2 a, which differ magnetically in that phase 1
      undergoes a full two-step SCO (T(1/2(1))=135 K and T(1/2(2))=90 K) whereas phase
      2 a remains high spin (HS) over all temperatures. The central distinction between
      these two materials lies in the presence of intermolecular pi-pi interactions
      generated by the crystal packing in 1, which are absent in 2 a. The isostructural
      selenocyanate analogue of 2 a, [Fe(NCSe)(2)(bdpp)], 2 b, undergoes a full two
      step SCO (T(1/2(1))=200 K and T(1/2(2))=125 K). Structural analyses of 1 and 2 b
      at a range of temperatures provide deep insight into their two-step SCO nature.
      Structural analysis of 1 at 25 K (1(LS-LS)), 123 K (1(LS-HS)) and 250 K (1(HS
      HS)) reveals two distinct iron(II) centres at each temperature, with ordered,
      alternating HS and LS (low spin) sites at the intermediate plateau (IP)
      temperatures. In contrast, structural analysis of 2 b at 90 K (2 b(LS)), 150 K (2
      b(LS/HS)) and 250 K (2 b(HS)) reveals one unique iron(II) centre at each
      temperature with an "averaged" LS/HS character at the IP temperature. Weak planes
      of diffuse scattering in the single-crystal X-ray diffraction patterns were
      observed for this phase at 90 and 150 K, indicating that 1D long range ordering
      of alternating HS/LS iron(II) centres occurs along the 1D coordination chains,
      but that there is no correlation between chains. The lack of observable diffuse
      scattering at 250 K suggests that the onset of the 1D structural ordering in the
      chain direction corresponds to the first step of the SCO and that this structural
      transition is electronically driven. The photomagnetic properties of both 1 and 2
      b have been investigated and show approximately 62 and 53 % photo-excitation of a
      HS metastable state at low temperatures and T(LIESST) values of 55 and 49 K,
      respectively. Relaxation studies on the HS fraction in 2 b fitted well to a
      stretched exponential model with kinetic parameters indicative of weak
      cooperativity.

PMID- 18803204
TI  - New benzo[h]quinoline-based ligands and their pincer Ru and Os complexes for
      efficient catalytic transfer hydrogenation of carbonyl compounds.
AB  - New benzo[h]quinoline ligands (HCN'N) containing a CHRNH2 (R=H (a), Me (b), tBu
      (c)) function in the 2-position were prepared starting from benzo[h]quinoline N
      oxide (in the case of ligand a) and 2-chlorobenzo[h]quinoline (for ligands b and
      c). These compounds were used to prepare ruthenium and osmium complexes, which
      are excellent catalysts for the transfer hydrogenation (TH) of ketones. The
      reaction of a with [RuCl2(PPh3)3] in 2-propanol at reflux afforded the terdentate
      CN'N complex [RuCl(CN'N)(PPh3)2] (1), whereas the complexes [RuCl(CN'N)(dppb)] (2
      4; dppb=Ph2P(CH2)4PPh2) were obtained from [RuCl2(PPh3)(dppb)] with a-c,
      respectively. Employment of (R,S)-Josiphos, (S,R)-Josiphos*, (S,S)-Skewphos, and
      (S)-MeO-Biphep in combination with [RuCl2(PPh3)3] and ligand a gave the chiral
      derivatives [RuCl(CN'N)(PP)] (5-8). The osmium complex [OsCl(CN'N)(dppb)] (12)
      was prepared by treatment of [OsCl2(PPh3)3] with dppb and ligand a. Reaction of
      the chloride 2 and 12 with NaOiPr in 2-propanol/toluene afforded the hydride
      complexes [MH(CN'N)(dppb)] (M=Ru 10, Os 14), through elimination of acetone from
      [M(OiPr)(CN'N)(dppb)] (M=Ru 9, Os 13). The species 9 and 13 easily reacted with
      4,4'-difluorobenzophenone, via 10 and 14, respectively, affording the
      corresponding isolable alkoxides [M(OR)(CN'N)(dppb)] (M=Ru 11, Os 15). The
      complexes [MX(CN'N)(P2)] (1-15) (M=Ru, Os; X=Cl, H, OR; P=PPh3 and
      P2=diphosphane) are efficient catalysts for the TH of carbonyl compounds with 2
      propanol in the presence of NaOiPr (2 mol %). Turnover frequency (TOF) values up
      to 1.8x10(6) h(-1) have been achieved using 0.02-0.001 mol % of catalyst. Much
      the same activity has been observed for the Ru--Cl, --H, --OR, and the Os--Cl
      derivatives, whereas the Os--H and Os--OR derivatives display significantly lower
      activity on account of their high oxygen sensitivity. The chiral Ru complexes 5-8
      catalyze the asymmetric TH of methyl-aryl ketones with TOF approximately 10(5) h(
      1) at 60 degrees C, up to 97 % enatiomeric excess (ee) and remarkably high
      productivity (0.005 mol % catalyst loading). High catalytic activity (TOF up to
      2.2x10(5) h(-1)) and enantioselectivity (up to 98 % ee) have also been achieved
      with the in-situ-generated catalysts prepared from [MCl2(PPh3)3], (S,R)-Josiphos
      or (S,R)-Josiphos*, and the benzo[h]quinoline ligands a-c.

PMID- 18803205
TI  - Comparison of the surprising metal-ion-binding properties of 5- and 6
      uracilmethylphosphonate (5Umpa2- and 6Umpa2-) in aqueous solution and crystal
      structures of the dimethyl and di(isopropyl) esters of H2(6Umpa).
AB  - 5- and 6-Uracilmethylphosphonate (5Umpa(2-) and 6Umpa(2-)) as acyclic nucleotide
      analogues are in the focus of anticancer and antiviral research. Connected
      metabolic reactions involve metal ions; therefore, we determined the stability
      constants of M(Umpa) complexes (M(2+)=Mg(2+), Ca(2+), Mn(2+), Co(2+), Cu(2+),
      Zn(2+), or Cd(2+)). However, the coordination chemistry of these Umpa species is
      also of interest in its own right, for example, the phosphonate-coordinated M(2+)
      interacts with (C4)O to form seven-membered chelates with 5Umpa(2-), thus leading
      to intramolecular equilibria between open (op) and closed (cl) isomers. No such
      interaction occurs with 6Umpa(2-). In both M(Umpa) series deprotonation of the
      uracil residue leads to the formation of M(Umpa-H)(-) complexes at higher pH
      values. Their stability was evaluated by taking into account the fact that the
      uracilate residue can bind metal ions to give M(2)(Umpa-H)(+) species. This has
      led to two further important insights: 1) In M(6Umpa-H)-cl the H(+) is released
      from (N1)H, giving rise to six-membered chelates (degrees of formation of ca. 90
      to 99.9 % with Mn(2+), Co(2+), Cu(2+), Zn(2+), or Cd(2+)). 2) In M(5Umpa-H)$-cl
      the (N3)H is deprotonated, leading to a higher stability of the seven-membered
      chelates involving (C4)O (even Mg(2+) and Ca(2+) chelates are formed up to
      approximately 50 %). In both instances the M(Umpa-H)-op species led to the
      formation of M(2)(Umpa-H)(+) complexes that have one M(2+) at the phosphonate and
      one at the (N3)(-) (plus carbonyl) site; this proves that nucleotides can bind
      metal ions independently at the phosphate and the nucleobase residues. X-ray
      structural analyses of 6Umpa derivatives show that in diesters the phosphonate
      group is turned away from the uracil residue, whereas in H(2)(6Umpa) the
      orientation is such that upon deprotonation in aqueous solution a strong hydrogen
      bond is formed between (N1)H and PO(3) (2-); replacement of the hydro gen with
      M(2+) gives the M(6Umpa-H)-cl chelates mentioned.

PMID- 18803207
TI  - An interrupted [4+3] cycloaddition reaction: a hydride shift (ene reaction)
      intervenes.

PMID- 18803206
TI  - Functionalization of imprinted nanopores in nanometer-thin organic materials.

PMID- 18803208
TI  - Biotinylated bi- and tetra-antennary glycoconjugates for Escherichia coli
      detection.
AB  - Glycans cover the surface of all mammalian cells. Several toxins and pathogens
      use these glycans to bind and infect the cell. Using a versatile modular
      synthetic strategy, we have developed biotinylated bi- and tetraantennary
      glycoconjugates to capture and detect E. coli and compared the capturing ability
      of these molecules to commercial polyclonal antibodies. Magnetic beads were
      coated with biotinylated glycoconjugate or antibody, and these beads were used to
      capture, isolate, and quantify bacterial recovery by using a luminescence assay.
      The glycoconjugate-coated magnetic beads outperformed antibody-coated magnetic
      beads in sensitivity and selectivity when compared under identical experimental
      conditions. Glycoconjugates could capture Escherichia coli from stagnant water,
      and the ability of a panel of glycoconjugates to capture a selection of
      pathogenic bacteria was also evaluated. To the best of our knowledge, this study
      represents the first comprehensive study that compares synthetic glycoconjugates
      and antibodies for E. coli detection. The glycoconjugates are also very stable
      and inexpensive. The results presented here are expected to lead to an increased
      interest in developing glycoconjugate-based high affinity reagents for
      diagnostics.

PMID- 18803209
TI  - Photocontrol of genomic DNA conformation by using a photosensitive gemini
      surfactant: binding affinity versus reversibility.

PMID- 18803210
TI  - Theoretical study of the human bradykinin-bradykinin B2 receptor complex.
AB  - The interaction of bradykinin (BK) with the bradykinin B2 receptor (B2R) was
      analyzed by using molecular modeling (MM) and molecular dynamics (MD)
      simulations. A homology model for B2R has been generated and the recently
      determined receptor-bound solid-state NMR spectroscopic structure of BK (Lopez et
      al., Angew. Chem. 2008, 120, 1692-1695; Angew. Chem. Int. Ed. 2008, 47, 1668
      1671) has been modeled into the binding pocket of the receptor to probe the
      putative ligand-receptor interface. The experimental hormone structure fitted
      well into the binding pocket of the receptor model and remained stable during the
      MD simulation. We propose a parallel orientation of the side chains for Arg1 and
      Arg9 in BK that is bound to B2R. The MD simulation study also allows the
      conformational changes that lead to the activated form of B2R to be analyzed. The
      hydrogen bond between N140 (3.35) and W283 (6.48) is the key interaction that
      keeps the receptor in its inactive form. This hydrogen bond is broken during the
      MD simulation due to rotation of transmembrane helix 3 (TM3) and is replaced by a
      new hydrogen bond between W283 (6.48) and N324 (7.45). We propose that this
      interaction is specific for the activated form of the bradykinin B2 receptor.
      Additionally, we compared and discussed our putative model in the context of the
      structural model of the partially activated rhodopsin (Rh*) and with the known
      biochemical and structural data.

PMID- 18803211
TI  - Quality control of herbal medicines by capillary electrophoresis: potential,
      requirements and applications.
AB  - Herbal preparations, particularly those from traditional Chinese or Indian
      medicine, are becoming increasingly popular in Europe and the USA. Their
      application is often based on long-term historic use rather than on scientific
      evidences; thus, analytical tools to assure their efficacy, safety and
      consistency are in great demand. This review evaluates the importance of CE for
      quality control of herbal medicinal products during the last five years. After
      briefly describing the general characteristics of natural products analysis by
      CE, numerous applications on medicinal plants or herbal products are summarized.
      These examples not only reflect the enormous variability of CE with respect to
      buffer systems and detection modes employed, but also indicate an increasing
      importance of this separation technique for quality control purposes compared
      with more established ones such as HPLC.

PMID- 18803212
TI  - Micellar electrokinetic capillary chromatography determination of alginic acid in
      pharmaceutical formulations after treatment with alginate lyase and UV detection.
AB  - A new highly specific and sensitive capillary electrophoresis method
      (electrokinetic chromatography with SDS) for the determination of the total
      alginic acid (AA) content in pharmaceutical formulations is described by means of
      capillary electrophoresis at 230 nm after treatment with alginate lyase [4.2.2.3]
      and separation of unsaturated products, Delta-oligomers (DeltaHexA-[HexA](n)), in
      particular, DP3 (DeltaHexA-HexA-HexA) and DP4 (DeltaHexA-HexA-HexA-HexA). Using a
      buffer constituted with 10 mM sodium borate and 50 mM SDS at pH 9.0, micellar
      electrokinetic capillary chromatography was able to determine with very high
      resolution the AA Delta-oligomers produced by the action of the lyase (mainly DP3
      and DP4) as one single species. The intra- and inter-day variations (CV%) were
      between 6.3 and 9.1 for migration time and between 2.5 and 5.7 for peak area,
      respectively. The calibration curve showed good linearity for the examined
      concentration range (60-360 ng) with an average correlation coefficient greater
      than 0.980. The lowest detection limit and the lowest quantitation limit of the
      method were 15 ng (0.25 mg/mL) and 40 ng (0.67 mg/mL), respectively. The intra-
      and inter-day variations in terms of CV% were 5.5 and 8.6%, respectively, and the
      intra- and inter-day accuracy was estimated to range from 4.1 to 8.9%, while the
      percent recoveries of AA were calculated to be 102, 97 and 93% for different AA
      amounts. Variations in temperatures, voltage and buffer composition in comparison
      with adopted conditions within a 10% limit do not modify the electrophoresis
      results. The evaluation of AA was performed in both solid and liquid
      pharmaceutical formulations also in the presence of other ingredients, in
      particular, aluminium, sodium and potassium bicarbonate, and emulsifying and
      flavouring agents. The quantitative results obtained were 101.2+/-3.4% of AA
      content in tablets and 98.4+/-2.8% in liquid formulation, in total conformity
      with the label claims.

PMID- 18803213
TI  - Fast assay of glucosamine in pharmaceuticals and nutraceuticals by capillary zone
      electrophoresis with contactless conductivity detection.
AB  - A novel capillary electrophoresis (CE) method with contactless conductivity
      detection suitable for the determination of glucosamine (GlAm) and K(+) in
      pharmaceuticals was devised. Under the optimum conditions (aqueous 30 mM acetate
      buffer of pH 5.2 as the background electrolyte; voltage 30 kV; 25 degrees C),
      GlAm (migrating as glucosaminium cation) was well separated from K(+) that could
      occur in the dosage forms as excipient. The CE analysis was performed in fused
      silica capillaries (50 microm i.d., 75 cm total length, 27 cm to detector) and
      the separation took <3 min. The calibration graphs were linear for both GlAm (100
      300 microg/mL; r(2)=0.997) and K(+) (15-75 microg/mL; r(2)=0.997) when using
      ethanolamine (100 microg/mL) as the internal standard. The LOD values (S/N=3)
      were 9.3 microg/mL for GlAm and 2.9 microg/mL for K(+). The method was applied to
      the assay of GlAm content in various dosage forms. Intermediate precision
      evaluated by determining the content of GlAm in a single formulation on 3
      consecutive days was characterized by RSD 2.35% (n=15). Acceptable accuracy of
      the CE method was confirmed by the added/found GlAm recovery experiments
      (recoveries 94.6-103.3%) and by statistical comparison of the results attained by
      the proposed CE and a reference HPLC method.

PMID- 18803214
TI  - Development and validation of an MEKC method for determination of nitrogen
      containing drugs in pharmaceutical preparations.
AB  - A fast and accurate micellar electrokinetic capillary chromatography method was
      developed for quality control of pharmaceutical preparations containing cold
      remedies as acetaminophen, salicylamide, caffeine, phenylephrine,
      pseudoephedrine, norephedrine and chlorpheniramine. The method optimization was
      realized on a Beckman P/ACE System MDQ instrument. The baseline separation of
      seven analytes was performed in an uncoated fused silica capillary internal
      diameter (ID)=50 microm using tris-borate (20 mM, pH=8.5) containing sodium
      dodecyl sulphate 30 mM BGE. On line-UV detection at 214 nm was performed and the
      applied voltage was 10 kV. The operating temperature was 25 degrees C. After
      experimental conditions optimization, the proposed method was validated. The
      evaluated parameters were: precision of migration time and of corrected peak area
      ratio, linearity range, limit of detection, limit of quantification, accuracy
      (recovery), ruggedness and applicability. The method was then successfully
      applied for the analysis of three pharmaceutical preparations containing some of
      the analytes listed before.

PMID- 18803215
TI  - A simple micellar electrokinetic capillary chromatographic method for the
      quantitative analysis of organic expectorants.
AB  - A simple and rapid micellar electrokinetic capillary chromatographic method is
      described for the separation and quantification of five expectorant drugs,
      including ambroxol (AMB), bromhexine (BRM), carbocysteine, guaiacol and
      guaifenesin. The drugs were separated in a mixed solution of phosphate buffer (35
      mM; pH 3.90) and acetonitrile (75:25, v/v) with sodium dodecylsulfate (120 mM) as
      the micellar source, and the separated drugs were directly monitored with UV
      detector (200 nm). Several key parameters affecting the separation and analysis
      of the drugs were studied and optimized. Based on the corrected peak-area ratios
      of the drugs to an internal standard (7-hydroxy-4-methyl-coumarin) versus the
      concentration of the drugs, the established method is applicable to quantify AMB
      and BRM each over 20-150 microM, carbocysteine over 100-1500 microM, guaiacol and
      guaifenesin each over 10-150 microM. The detection limits (S/N=3; 0.5 psi, 5 s
      injection) of the method for the analytes are in the range of 3.0-5.0 microM
      (except that of carbocysteine at 30 microM). The precision (relative standard
      deviation) and accuracy (relative error) of the method for the intra-day (n=3)
      and inter-day (n=5) analyses of the analytes at three levels are all below 4%.
      The method is speedy with a run time of about 6 min for the analysis of the five
      analytes. Application of this method to the analysis of AMB and BRM in
      pharmaceutical preparations or AMB in the urine of a dosed subject proved simple
      and effective.

PMID- 18803216
TI  - Strategies in method development to quantify enantiomeric impurities using CE.
AB  - The growing number of chiral new drug substances requires increasing efforts in
      developing enantioselective methods. According to International conference on
      Harmonization guidelines, one should quantify the enantiomeric impurity of 0.1%
      relative to the major constituent. Capillary electrophoresis has evolved into an
      important tool for the separation of chiral drugs. The common strategies consist
      of two steps: firstly, initial separation conditions are evaluated. This
      screening usually focuses on the selection of the appropriate chiral selector. In
      our study 22 neutral, anionic or cationic cyclodextrins were dissolved in
      phosphate buffer (pH 2.5, 50 mM, CD conc.: 2.0%). Then they were investigated for
      the separation of 14 chiral compounds. Secondly, the obtained initial conditions
      for the enantiomeric separation were optimized in terms of resolution and
      analysis time. In our approach, important optimized factors including the
      concentration of the chiral selector (1-10%), the pH of the buffer (2.0-9.0), and
      the percentage of organic modifier (0-15%) were studied. This common strategy was
      completed by elaborating final requirements for the quantification of the
      enantiomeric impurity. A resolution between 3 and 4 was found to be necessary for
      the racemic mixture during the screening and optimization steps, in order to
      later allow for peak overloading and thus to sufficiently increase the signal-to
      noise ratio. The complete strategy was conducted for atenolol, isoprenaline,
      verapamil and mandelic acid.

PMID- 18803217
TI  - Comparison of CZE, open-tubular CEC and non-aqueous CE coupled to electrospray MS
      for impurity profiling of drugs.
AB  - Open-tubular CEC and non-aqueous CE (NACE) methods were developed for the
      analysis of six pharmaceutical compounds and their respective process-related
      impurities, comprising 22 analytes in total with a range of functional groups and
      lipophilicities. These methods were assessed for orthogonality of analyte
      separation with respect to existing CZE-ESI-MS and HPLC-ESI-MS methods, in order
      to complement a generic analytical strategy for impurity profiling of
      pharmaceutical compounds. Open-tubular CEC, using etched and chemically modified
      capillaries, induced weak reversed-phase-type interactions between some of the
      analytes and the bonded phases (0.811<k(app)<0.996). However, the separations
      were primarily influenced by electrophoretic mobility rather than chromatographic
      retention, and hence no significant change in selectivity compared with CZE was
      observed. NACE optimum separating conditions were 10 mM ammonium acetate-100 mM
      acetic acid in methanol far UV acetonitrile (1/1 v/v ratio). The ion-pair
      reagents triethylamine or dimethylhexylamine did not induce further changes in
      selectivity, but tridecafluoroheptanoic acid significantly modified the
      electrophoretic mobility of bases. The results indicate that one of three generic
      CZE methods previously reported should be replaced by NACE, due to its improved
      separation capabilities. The NACE-ESI-MS method complements the two CZE-ESI-MS
      and the four HPLC-ESI-MS methods recommended in a previous publication; these
      together form the basis of a generic approach to impurity profiling of
      pharmaceutical compounds.

PMID- 18803218
TI  - Cyclodextrin-based nonaqueous electrokinetic chromatography with UV and mass
      spectrometric detection: application to the impurity profiling of amiodarone.
AB  - The potential of nonaqueous electrokinetic chromatography (NAEKC) using
      cyclodextrins (CD) for the analysis of basic drugs and related compounds was
      evaluated. Both UV absorbance and mass spectrometric (MS) detection were
      employed. Addition of neutral CD to the NA background electrolyte did not
      significantly enhance the separation of a test mixture of basic drugs, and no
      change in selectivity was observed. In contrast, anionic single-isomer-sulfated
      CD strongly added to the selectivity of the NAEKC system inducing an improved
      resolution among the test compounds and increasing the migration time window. The
      applicability of the NAEKC system using anionic CD is demonstrated by the
      profiling of a sample of the drug amiodarone that had been stored for 1 year at
      room temperature. Amiodarone is poorly soluble in water. NAEKC-UV analysis
      indicated the presence of at least seven impurities in the amiodarone sample. In
      order to identify these compounds, the NAEKC system was coupled directly to
      electrospray ionization (ESI) ion-trap MS. The total of detected impurities
      increased to 12 due to the added sensitivity and selectivity of MS detection.
      Based on the acquired MS/MS data, three sample constituents could be identified
      as 'known' impurities (British Pharmacopoeia), whereas for three unknown
      impurities molecular structures could be proposed. Estimated limits of detection
      for amiodarone using the NAEKC method were 1 microg/mL with UV detection and 15
      ng/mL with ESI-MS detection (full-scan). Based on relative responses, the
      impurity content of the stored drug substance was estimated to be 0.33 and 0.47%
      using NAEKC-UV and NAEKC-ESI-MS, respectively.

PMID- 18803219
TI  - Chiral separation of the plant lignan matairesinol by capillary electrophoresis.
AB  - Lignans are dimeric phenylpropanoid compounds in plants that enjoy increasing
      medicinal interest because of their phytoestrogen activity. Lignans are chiral
      compounds and for most natural occurring lignans, chirality is not known.
      Separation of racemic matairesinol by CE in a non-coated silica capillary with
      carboxymethyl-beta-cyclodextrin as chiral selector in phosphate buffer was
      successful. Electrolyte and selector concentrations and pH were systematically
      optimized in order to obtain baseline separation and short analysis times.
      Matairesinol from safflower fruit was determined as (-)-enantiomer. Quantitation
      results for matairesinol with the optimized method after calibration with
      authentic lignan were very similar to those by HPLC. The limit of detection is 2
      microg/mL sample by DAD detection.

PMID- 18803220
TI  - Field-amplified on-line sample stacking for simultaneous enantioseparation and
      determination of some beta-blockers using capillary electrophoresis.
AB  - A capillary electrophoresis method using carboxymethyl-beta-cyclodextrin as the
      chiral selector and mixture of methanol and ethanol as the organic additive was
      successfully developed for the simultaneous enantioseparation and determination
      of six beta-blockers, namely, carteolol, atenolol, sotalol, metoprolol, esmolol
      and propranolol in this paper. The most suitable running buffer for
      enantioseparation was found to be the solution of 20 mmol/L NaH(2)PO(4)
      Na(2)HOP(4) (pH 5.5) containing 1.5% w/v carboxymethyl-beta-cyclodextrin, 5% v/v
      methanol and 5% v/v ethanol. Furthermore, field-amplified sample injection as an
      on-line sample stacking method was developed in order to increase the detection
      sensitivity. The experimental conditions for both simultaneous enantioseparation
      and the field-amplified sample injection method had been investigated in detail.
      Under the optimum conditions, the detection limits (defined as S/N=3) of this
      method were 0.01, 0.05, 0.05, 0.05, 0.05 and 0.5 microg /mL for (+/-) carteolol,
      (+/-) atenolol, (+/-) sotalol, (+/-) metoprolol, (+/-) esmolol and (+/-)
      propranolol, respectively, which were much lower than those of the conventional
      methods. The enhancement factors were greatly improved by 25-fold for the
      enantiomers of the beta-blockers except five-fold for (+/-) propranolol.
      Eventually, the proposed method has been applied for the analysis of human serum
      sample.

PMID- 18803221
TI  - Evaluation of glycosylation for quality assurance of antibody pharmaceuticals by
      capillary electrophoresis.
AB  - The development of monoclonal antibody (mAb) pharmaceuticals has rapidly
      generated in this decade, and there are currently 23 FDA-approved mAb
      pharmaceuticals. Carbohydrate chains in mAb pharmaceuticals play important roles
      for the expression of their biological activities such as antibody-dependent
      cellular cytotoxicity, whereas the oligosaccharide profile is easily changed
      depending on the manufacturing conditions. Therefore, the evaluation of
      carbohydrate chains in detail is quite important for quality control in the
      development of mAb from early phases, but oligosaccharides in mAb have high
      heterogeneity and full characterization of oligosaccharide moiety in mAb has been
      a challenging target. Capillary electrophoresis (CE) is a powerful tool for the
      evaluation of glycan occupancy and oligosaccharide profile. This review focuses
      mainly on the application of CE to the analytical studies on glycosylation in mAb
      pharmaceuticals developed in our laboratory. The related techniques including the
      full-image microchip isoelectric focusing and the newly developed mass
      spectrometry technologies are also shown. The combination of the techniques
      described in this review will be a good guide for the evaluation of glycosylation
      for quality assurance of antibody pharmaceuticals by CE from the early stage of
      the development to the marketing stage.

PMID- 18803222
TI  - Analysis of the molecular size distribution of polyethylene glycols by CE-UV
      versus HPLC with evaporative light scattering detection.
AB  - A simple capillary zone electrophoresis method has been developed for the
      separation of polyethylene glycols (PEGs) consisting of differing amounts of
      polymers with different monomer numbers up to an average molecular mass of 1500.
      To provide both charge and detectability, the analytes were derivatized with
      phthalic anhydride according to a conventional method and a newly developed
      microwave-assisted method. While obtaining nearly equal amounts of single and
      double esterificated PEGs with the conventional method, the fraction of single
      derivatized PEGs is considerably reduced by microwave-assisted reaction. In order
      to compare the capillary zone electrophoresis results, an HPLC method with
      evaporative light scattering detection has been established. This method was
      successfully applied to the analysis of underivatized PEG 400, 1000 and 1500.

PMID- 18803223
TI  - Applications of CE SDS gel in development of biopharmaceutical antibody-based
      products.
AB  - CE SDS gel technique offers many advantages over the traditional labor-intensive
      SDS PAGE slab gel technology. The CE-based method has increasingly been applied
      to many protein analysis applications. Specific examples are provided for
      monoclonal antibody (mAb), though the technique can be adapted to many other
      therapeutic protein products. Applications of CE SDS gel method using Beckman
      PA800 with UV detection are presented and discussed with respect to mAb analysis,
      such as purity, quantitation of non-glycosylated heavy chain (NGHC) peak,
      identity, and stability. The stability of mAb is evaluated with respect to
      formulation buffer, accelerated temperature stress, UV light-exposure, and high
      pH conditions. Both reducing and non-reducing CE SDS gel conditions were applied
      and optimized to characterize mAb products. The data presented provides a "taste"
      of what CE SDS gel method can do to support the development of mAb products from
      early clone screening for product quality to the final product characterization.
      Since the CE SDS gel method is automatable, quantitative, robust, and allows for
      relatively high throughput, it provides both great analytical capacity and
      product coverage for a wide spectrum of protein product development in
      biopharmaceutical industry.

PMID- 18803224
TI  - Fluorescence-based Western blotting for quantitation of protein biomarkers in
      clinical samples.
AB  - Since most high throughput techniques used in biomarker discovery are very time
      and cost intensive, highly specific and quantitative analytical alternative
      application methods are needed for the routine analysis. Conventional Western
      blotting allows detection of specific proteins to the level of single isotypes
      while its quantitative accuracy is rather limited. We report a novel and improved
      quantitative Western blotting method. The use of fluorescently labelled secondary
      antibodies strongly extends the dynamic range of the quantitation and improves
      the correlation with the protein amount (r=0.997). By an additional fluorescent
      staining of all proteins immediately after their transfer to the blot membrane,
      it is possible to visualise simultaneously the antibody binding and the total
      protein profile. This allows for an accurate correction for protein load.
      Applying this normalisation it could be demonstrated that fluorescence-based
      Western blotting is able to reproduce a quantitative analysis of two specific
      proteins in blood platelet samples from 44 subjects with different diseases as
      initially conducted by 2D-DIGE. These results show that the proposed fluorescence
      based Western blotting is an adequate application technique for biomarker
      quantitation and suggest possibilities of employment that go far beyond.

PMID- 18803225
TI  - Electrophoresis studies on the contaminating glycosaminoglycans in commercially
      available hyaluronic acid products.
AB  - Hyaluronic acid (HA) samples showing inhibition effect on digestion with
      testicular hyaluronidase (HAase) were found from 16 commercially available HA
      products, which were supplied from 11 different manufacturers. Most of these HA
      samples (six samples) were derived from the rooster comb, and one sample was
      derived from the human umbilical cord. HA oligosaccharides produced by exhaustive
      digestion of these HA samples with testicular HAases were monitored by capillary
      electrophoresis, and we found that a few HA samples gave no oligosaccharide
      products. Detailed analysis of HA samples by cellulose acetate membrane
      electrophoresis revealed that the HA samples were not digested with HAase because
      of the presence of a small amount of dermatan sulfate (DS). Analysis of
      disaccharide units of these HA samples produced by digestion with chondroitinase
      ABC supported the observations. And the content of DS in the sample was estimated
      to be ca. 8%. In contrast, these HA samples were easily digested with bacterial
      hyaluronate lyases from Streptomyces hyalurolyticus and Streptococcus
      dysgalactiae and gave endproducts of unsaturated disaccharide or unsaturated
      tetra- or hexasaccharides. The results suggested that the inhibitory effect of DS
      on HAase is specific to endo-type hydrolase (i.e. testicular HAase). In addition,
      pharmaceutical preparations of HA derived from rooster comb were easily digested
      with testicular HAase. These findings will be useful information for clinical or
      cosmetic use of HA preparations in terms of their half-life.

PMID- 18803226
TI  - Extracts of Liriopsis tuber protect AMPA induced brain damage and improve memory
      with the activation of insulin receptor and ERK I/II.
AB  - The brain insulin receptor and ERK I/II are known to play an important role in
      memory formation and neuroprotection. A series of experiments was designed to
      explore if Liriopsis tuber (LT) extracts could exhibit neuroprotection and memory
      enhancing actions. LT was extracted with 70% methanol and subsequently
      fractionated into chloroform (fraction C), chloroform/methanol-(3:1) (fraction
      CM), methanol-soluble (fraction M) and methanol-insoluble, water-soluble
      fractions (fraction A). The LT fractions (T, C, M, A) significantly inhibited the
      cortical depolarization induced by AMPA in cortical slices of rats. In addition,
      these fractions were also effective in promoting memory in the passive avoidance
      test in mice. To gain insight into the mechanism of memory enhancing effects by
      Liriopsis tuber extracts, the activities of hippocampal insulin receptors and ERK
      I/II were tested in rats. Extract of LT (T) dramatically stimulated tyrosine
      phosphorylation of the insulin receptor, while fraction C of LT also
      significantly stimulated the same. In addition, ERK I/II were stimulated and
      cholinesterase activities were inhibited by fractions T, C, M and A in the rat
      hippocampus. These results suggest that Liriopsis tuber extracts may exert
      neuroprotection and memory enhancing effects via activation of the insulin
      receptor and ERK I/II as well as inhibiting cholinesterase.

PMID- 18803227
TI  - Inhibitory activities of Cassia tora and its anthraquinone constituents on
      angiotensin-converting enzyme.
AB  - As a component of our program that pertains to the isolation of antihypertensive
      agents derived from natural products, we screened the bioactivity of seeds from
      raw and roasted Cassia tora via angiotensin converting enzyme (ACE) inhibitory
      assays. We found that both of the MeOH extracts from the raw and roasted C. tora
      exhibited significant inhibitory properties against ACE, demonstrating more than
      50% inhibition at a concentration of 163.93 microg/mL. Emodin (3), alaternin (4),
      gluco-obtusifolin (5), cassiaside (6), gluco-aurantioobtusin (7), cassitoroside
      (8), toralactone gentiobioside (9), and chrysophanol triglucoside (10) had been
      previously isolated; however, questin (1) and 2-hydroxyemodin 1-methylether (2)
      were isolated from C. tora for the first time in this study. Among them, only
      anthraquinone glycoside (7) demonstrated marked inhibitory activity against ACE,
      with an IC(50) value of 30.24 +/- 0.20 microM. Conversely, aurantioobtusin (7a),
      obtained from the acid hydrolysis of 7, showed no activity. Further inhibitory
      kinetics analyzed from Lineweaver-Burk plots showed 7 to be a competitive
      inhibitor with a Ki value of 8.3 x 10(-5) M. Moreover, compound 7 showed marked
      inhibitory and scavenging activities with an IC(50) value of 49.64 +/- 0.37
      microM (positive control; trolox: 26.07 +/- 1.05 microM) for total reactive
      oxygen species generation, and 4.60 +/- 1.12 microM (positive control;
      penicillamine: 0.24 +/- 0.04 microM) for ONOO(-).

PMID- 18803228
TI  - Genotoxicity of Achillea millefolium essential oil in diploid cells of
      Aspergillus nidulans.
AB  - The essential oil of Achillea millefolium is commonly used in folk medicine for
      the treatment of several diseases and has been demonstrated previously to exert
      an in vitro antimicrobial activity against human pathogens. Current study
      investigates the genotoxic activity of A. millefolium oil. The oil's major
      constituents are: chamazulene (42.15%), sabinene (19.72%), terpin-4-ol (5.22%),
      beta-caryophyllene (4.44%) and eucalyptol (3.10%), comprising 74.63% of the
      total. The oil's genotoxic evaluation was performed at concentrations of 0.13
      microL/mL, 0.19 microL/mL and 0.25 microL/mL with a heterozygous diploid strain
      of Aspergillus nidulans, named A757//UT448, with green conidia. A statistically
      significant increasing number of yellow and white mitotic recombinants, per
      colony, of the diploid strain was reported after oil treatment with 0.19
      microL/mL and 0.25 microL/mL concentrations. The genotoxicity of the oil was
      associated with the induction of mitotic non-disjunction or crossing-over by oil.

PMID- 18803229
TI  - The inhibition of free radical generation by preparations of Harpagophytum
      procumbens in vitro.
AB  - Harpagophytum procumbens (Hp), commonly known as Devil's Claw has been used as a
      traditional treatment for a variety of illnesses for centuries. Since the early
      twentieth century, it has become a popular antiinflammatory and analgesic
      preparation amongst European herbalists for supportive or adjuvant treatment of
      degenerative joint diseases. Extracts of Hp tubers have demonstrated
      antiinflammatory and analgesic effects in animal models of inflammation and in
      human trials. The mechanism(s) of action responsible for these attributes,
      however, remain to be elucidated. Reactive oxygen species generated in acute and
      chronic inflammatory diseases are known to be cytotoxic and can cause tissue
      damage. In this study, a root tuber extract (Hp extract) and commercially
      available tincture (Hp tincture) were investigated for antioxidant
      characteristics using in vitro test systems. Both preparations were found to
      effectively scavenge DPPH radical, inhibit nitrite levels in supernatants
      harvested from LPS-stimulated RAW 264.7 macrophages, and cause dose-dependent
      suppressions in the detection of fMLP- and AA-induced neutrophil MPO. The
      antioxidant effects demonstrated for both preparations of Hp may contribute to
      the antiinflammatory and analgesic properties observed for the plant.

PMID- 18803230
TI  - Comparative analysis between Chamomilla recutita and corticosteroids on wound
      healing. An in vitro and in vivo study.
AB  - The comparison of chamomile and corticosteroids for treating ulcers was done in
      vitro and in vivo. The experimental groups were: control; chamomile recutita;
      triamcinolone acetonide and clobetasol propionate. For the in vitro study the
      cell viability of fibroblasts cultured for 24 h in media conditioned by the
      substances was obtained by the MTT reduction analysis. For the in vivo study, 125
      male rats were submitted to experimental ulcers treated or not (control) by the
      substances tested. At 1, 3, 5, 7 and 14 days later 5 animals of each group were
      sacrificed. The lesions were analyzed by means of clinical observation and
      histological wound-healing grading. Data were compared by ANOVA (p <or= 0.05).
      All experimental groups presented positive cell viability in 24 h. The cultures
      treated with chamomile presented the smallest cell viability. All animals of the
      chamomile group exhibited complete wound healing 9 days before the other groups.
      Complete repaired lesions were observed after 5 days of treatment only in the
      chamomile group. Animals treated with chamomile presented significantly faster
      wound healing in comparison to those treated with corticosteroids. Based on the
      conditions of this study, we concluded that chamomile in comparison to
      corticosteroids promotes faster wound healing process.

PMID- 18803231
TI  - Antiaging effect of Cordyceps sinensis extract.
AB  - This experiment studied the effect of Cordyceps sinensis extract (CSE) on mice
      aged by d-galactose and castrated rats to analyse its antiaging effect. Water
      maze and step-down type avoidance tests were used to examine the effect of CSE on
      learning and memory. CSE shortened escape latency, prolonged step-down latency
      and decreased the number of errors in mice aged by d-galactose. The effect of CSE
      on the sexual function of castrated rats was evaluated by measuring the penis
      erection latency, mount latency and ejaculation latency. CSE appeared to shorten
      penis erection latency and mount latency in castrated rats. The study also
      measured the effect of CSE on the activity of age-related enzymes. The results
      showed that CSE improved the activity of superoxide dismutase, glutathione
      peroxidase and catalase and lowered the level of lipid peroxidation and monoamine
      oxidase activity in the aged mice. The study demonstrated that CSE can improve
      the brain function and antioxidative enzyme activity in mice with d-galactose
      induced senescence and promote sexual function in castrated rats. All of these
      findings suggest that CSE has an antiaging effect.

PMID- 18803233
TI  - Increased bone mass, altered trabecular architecture and modified growth plate
      organization in the growing skeleton of SOCS2 deficient mice.
AB  - Suppressor of cytokine signalling-2 (SOCS2) negatively regulates the signal
      transduction of several cytokines. Socs2(-/-) mice show increased longitudinal
      skeletal growth associated with deregulated GH/IGF-1 signalling. The present
      study examined the role of SOCS2 in endochondral ossification and trabecular and
      cortical bone formation, and investigated whether pro-inflammatory cytokines
      associated with pediatric chronic inflammatory disorders mediate their effects
      through SOCS2. Seven-week-old Socs2(-/-) mice were heavier (27%; P < 0.001) and
      longer (6%; P < 0.001) than wild-type mice. Socs2(-/-) tibiae were longer (8%; P
      < 0.001) and broader (18%; P < 0.001) than that of wild-type mice, and the Socs2(
      /-) mice had wider growth plates (24%; P < 0.001) with wider proliferative and
      hypertrophic zones (10% (P < 0.05) and 14% (P < 0.001) respectively). Socs2(-/-)
      mice showed increased total cross-sectional bone area (16%: P < 0.001), coupled
      to increased total tissue area (17%; P < 0.05) compared to tibia from wild-type
      mice. Socs2(-/-) mice showed increased percent bone volume (101%; P < 0.001),
      trabecular number (82%; P < 0.001) and trabecular thickness (11%; P < 0.001),
      with associated decreases in trabecular separation (19%; P < 0.001). TNFalpha
      exposure to growth plate chondrocytes for 48 h increased SOCS2 protein
      expression. Growth of metatarsals from 1-day-old Socs2(-/-) and Socs2(+/+) mice,
      as well as expression of Aggrecan, Collagen Type II and Collagen Type X, were
      inhibited by TNFalpha, with no effect of genotype. Our data indicate that
      physiological levels of SOCS2 negatively regulate bone formation and endochondral
      growth. Our results further suggest that pro-inflammatory cytokines mediate their
      inhibitory effects on longitudinal bone growth through a mechanism that is
      independent of SOCS2.

PMID- 18803232
TI  - Sustained NF-kappaB activation produces a short-term cell proliferation block in
      conjunction with repressing effectors of cell cycle progression controlled by E2F
      or FoxM1.
AB  - NF-kappaB transcription factors induce a host of genes involved in pro
      inflammatory/stress-like responses; but the collateral effects and consequences
      of sustained NF-kappaB activation on other cellular gene expression programming
      remain less well understood. Here enforced expression of a constitutively active
      IKKbeta T-loop mutant (IKKbetaca) drove murine fibroblasts into transient growth
      arrest that subsided within 2-3 weeks of continuous culture. Proliferation arrest
      was associated with a G1/S phase block in immortalized and primary early passage
      MEFs. Molecular analysis in immortalized MEFs revealed that inhibition of cell
      proliferation in the initial 1-2 weeks after their IKKbetaca retroviral infection
      was linked to the transient, concerted repression of essential cell cycle
      effectors that are known targets of either E2F or FoxM1. Co-expression of a
      phosphorylation resistant IkappaBalpha super repressor and IKKbetaca abrogated
      growth arrest and cell cycle effector repression, thereby linking IKKbetaca's
      effects to canonical NF-kappaB activation. Transient growth arrest of IKKbetaca
      cells was associated with enhanced p21 (cyclin-dependent kinase inhibitor 1A)
      protein expression, due in part to transcriptional activation by NF-kappaB and
      also likely due to strong repression of Skp2 and Csk1, both of which are FoxM1
      direct targets mediating proteasomal dependent p21 turnover. Ablation of p21 in
      immortalized MEFs reduced their IKKbetaca mediated growth suppression. Moreover,
      trichostatin A inhibition of HDACs alleviated the repression of E2F and FoxM1
      targets induced by IKKbetaca, suggesting chromatin mediated gene silencing in
      IKKbetaca's short term repressive effects on E2F and FoxM1 target gene
      expression.

PMID- 18803234
TI  - In vitro differentiation of human calvarial suture derived cells with and without
      dexamethasone does not induce in vivo-like expression.
AB  - Osteogenic supplements are a requirement for osteoblastic cell differentiation
      during in vitro culture of human calvarial suture-derived cell populations. We
      investigated the ability of ascorbic acid and beta-glycerophosphate with and
      without the addition of dexamethasone to stimulate in vivo-like osteoblastic
      differentiation. Cells were isolated from unfused and prematurely fused suture
      tissue from patients with syndromic and non-syndromic craniosynostosis and
      cultured in each osteogenic medium for varying lengths of time. The effect of
      media supplementation was investigated with respect to the ability of cells to
      form mineralised bone nodules and the expression of five osteodifferentiation
      marker genes (COL1A1, ALP, BSP, OC and RUNX2), and five genes that are
      differentially expressed during human premature suture fusion (GPC3, RBP4,
      C1QTNF3, WIF1 and FGF2). Cells from unfused sutures responded more slowly to
      osteogenic media but formed comparable bone nodules to fused suture-derived cells
      after 16 days of culture in either osteogenic media. However, gene expression
      differed between unfused and fused suture-derived cells, as did expression in
      each osteogenic medium. When compared to expression in the explant tissue of
      origin, neither medium induced a level or profile of gene expression similar to
      that seen in vivo. Overall, our results demonstrate that cells from the same
      suture that are isolated during different stages of morphogenesis in vivo,
      despite being de-differentiated to a similar level in vitro, respond uniquely and
      differently to each osteogenic medium. Further, we suggest that neither cell
      culture medium recapitulates differentiation via activation of the same genetic
      cascades as occurs in vivo.

PMID- 18803235
TI  - Effects of Red Ginseng extract on ultraviolet B-irradiated skin change in C57BL
      mice.
AB  - Red Ginseng (the roots of Panax ginseng C.A. Meyer) is used clinically in China,
      Korea and Japan for various diseases, including atherosclerosis, hypertension and
      stress etc. Although Red Ginseng roots have traditionally been thought to have
      antiageing effects, the basis for this hearsay is unclear. This study examined
      the effects of Red Ginseng extract on ultraviolet B (UVB)-irradiated skin ageing
      in mice. Oral administration of Red Ginseng extract (20 or 60 mg/kg, twice daily)
      prevented UVB-irradiated skin damage (increases of skin thickness and
      pigmentation, and reduction of skin elasticity). Furthermore, Red Ginseng extract
      inhibited the increases of epidermis and corium thickness induced by UVB
      irradiation. Red Ginseng extract inhibited the increase of skin TGF-beta1 content
      induced by UVB irradiation. These findings suggest that the protective action of
      Red Ginseng extract against UVB-irradiated skin ageing may be due partly to an
      inhibition of the increase of skin TGF-beta1 induced by UVB irradiation. In
      conclusion, the oral administration of Red Ginseng extract may be useful as a
      health supplement for protection against photoageing.

PMID- 18803236
TI  - Adult dorsal root ganglia sensory neurons express the early neuronal fate marker
      doublecortin.
AB  - It has been widely accepted that doublecortin (DCX) may represent a neuronal fate
      marker transiently expressed by immature neurons during development of the
      central and peripheral nervous tissue and in neurogenic areas of the adult brain.
      Previous work described the presence of DCX in the developing dorsal root ganglia
      (DRG), structures of the peripheral nervous system originating from the neural
      crest, but no information is available on its expression in adulthood. To this
      purpose, we have performed an immunohistochemical and biochemical analysis for
      DCX expression in DRG from adult male mice and rats. To our surprise, we
      demonstrated that the majority of DRG neurons do express DCX, both in somata and
      in fibers. DCX(+) cells have been characterized morphologically and
      phenotypically with well-established markers of DRG neuronal subpopulations. A
      large number of DCX(+) cells belong to the small and medium-sized nociceptive
      neurons. Additionally, DCX immunoreactivity is present in the spinal cord dorsal
      horns, the projection area of DRG neurons. The novel and unexpected localization
      for DCX protein opens up new, interesting vistas on the functional role of this
      protein in mature neurons and in particular in sensory neurons.

PMID- 18803237
TI  - Morphological differences between wild-type and transgenic superoxide dismutase 1
      lumbar motoneurons in postnatal mice.
AB  - Quantitative analysis of the dendritic arborizations of wild-type (WT) and
      superoxide dismutase 1 (SOD1) postnatal mouse motoneurons was performed following
      intracellular staining and 3D reconstructions with Neurolucida system. The
      population of lumbar motoneurons was targeted in the caudal part of the L5
      segment, and all labeled motoneurons were located within the same ventrolateral
      pool. Despite the similar size of the soma and the mean diameter of primary
      dendrites, the dendritic arborizations of the WT and SOD1 motoneurons showed
      significant differences in terms of their morphometric parameters. The metric and
      topological parameters of dendrites show that the total dendritic length and
      surface area and total number of segments, branching nodes, and tips per
      motoneuron were significantly higher in SOD1 motoneurons. Our main finding
      concerns a proliferation of dendritic branches starting at about 100 microm from
      the soma in the SOD1 motoneurons. However, the longest and mean dendritic paths
      from soma to terminations were similar, giving a comparable envelope of the
      dendritic fields. Indeed, the SOD1 motoneurons were larger as a result of
      abnormal branching. The results suggest that a defect in pruning mechanisms
      occurs during this developmental period. The abnormal growth of the dendritic
      arborizations and the reduced excitability of postnatal SOD1 motoneurons could be
      a neuroprotective response and would represent an early compensatory mechanism
      against the activity-induced toxicity.

PMID- 18803238
TI  - Functional foveae in an electrosensory system.
AB  - Several species of Mormyrid weakly electric fish have a mobile chin protuberance
      that serves as a mobile antenna during prey detection, tracking behaviors, and
      foraging for food. It has been proposed that it constitutes a fovea of the
      electrosensory system. The distribution of the three types of receptor organs
      involved in active imaging of the local surroundings, prey detection, and passive
      electroreception, and their central projection to the electrosensory lobe (ELL),
      have been studied in Gnathonemus petersii. Density distributions were compared
      for different body regions. Primary afferent projections were labeled with
      biocytin or biotinylated dextrans. This showed that there is considerable central
      "over-representation" of the mandibular and nasal regions of the sensory surface
      involved in electrolocation, at the expense of the other body regions
      investigated. This over-representation is not a mere effect of the very high
      density of receptor organs in these areas, but is found to be due to central
      magnification. This magnification differs between the subclasses of
      electroreceptors, suggesting a functional segregation in the brain. We conclude
      that the chin protuberance and the nasal region are the regions of greatest
      sensitivity for the resistive, capacitive, and low-frequency characteristics of
      the environment, and are probably most important in prey detection, whereas other
      regions of the skin with a lesser resolution and sensitivity to phase distortion
      of the EOD, in particular the trunk, are probably designed for imaging larger,
      inanimate features of the environment. Our data support the hypothesis that the
      chin appendage and nasal region are functionally distinct electrosensory foveae.

PMID- 18803239
TI  - Altered olfactory epithelial structure and function in feline models of
      mucopolysaccharidoses I and VI.
AB  - The mucopolysaccharidoses (MPS) are a family of lysosomal storage diseases
      resulting in developmental defects and, in some types, mental retardation and
      other neurological symptoms. To gain insight into the neurological dysfunction in
      MPS, we examined the morphology of olfactory epithelia (OE) and physiology of
      olfactory receptor neurons (ORNs) in cat models of MPS I, a type in which
      neuronal lesions are prominent, and MPS VI, in which they are essentially absent.
      Histopathology showed that both groups of MPS-affected cats had significantly
      thinner OE than controls. Although immature and mature ORNs were present in both
      MPS I and VI affected OE, the OE of MPS I-affected cats was structurally
      disorganized. ORN function was assessed with calcium imaging and patch-clamp
      recording. Few viable ORNs were recovered from MPS VI cats, but these exhibited
      normal responses to odors and pharmacological stimuli. In contrast, viable ORNs
      were as prevalent in MPS I as in controls but were significantly less likely to
      respond to odor stimuli, although other responses were normal. Disrupted OE
      organization and impaired ORN function in MPS I, but not MPS VI, corresponds to
      the central nervous system lesions found in MPS I but not MPS VI. These data
      represent the first neurophysiological correlate of this correspondence and have
      implications both for understanding the role of glycosaminoglycans in maintenance
      of the OE and for targeting further research into the basis for and treatment of
      the neurological consequences of MPS disorders.

PMID- 18803240
TI  - Selective contribution of interleukin-6 and leptin to brain inflammatory signals
      induced by systemic LPS injection in mice.
AB  - This study aimed to address the relative contributions of the proinflammatory
      cytokine interleukin-6 (IL-6) and the cytokine-like hormone leptin to the genomic
      activation of brain cells during lipopolysaccharide (LPS)-induced systemic
      inflammation. Wildtype and IL-6KO mice were injected with LPS (50 microg/kg,
      intraperitoneally) and the brains analyzed by immunohistochemistry and reverse
      transcriptase polymerase chain reaction (RT-PCR). LPS induced a pronounced
      nuclear translocation of the signal transducer and activator of transcription
      (STAT3) throughout the brains of wildtype mice, an effect that was significantly
      diminished, but not abolished, in the IL-6KOs. The remnant STAT3-activation,
      although still observed within some of the same areas activated by IL-6, was most
      intense in ependymal and meningial cells and along distinct blood vessels
      throughout the brain. This expression was almost totally abolished in the
      presence of an anti-leptin antiserum. Interestingly, the induction of
      cyclooxygenase 2 and microsomal prostaglandin E synthase (mPGES), the rate
      limiting enzymes for synthesis of PGE2 by LPS, was diminished to a degree that
      correlated with the absence of IL-6 but not entirely with leptin. These results
      demonstrate that the induction of the inflammatory pathway in the brain is
      mediated by both IL-6 and leptin, which appear to work in tandem. Unlike IL-6,
      however, the contribution of leptin to this response was limited to distinct cell
      types/brain areas and STAT3-responsive target genes implicated in the brain
      controlled sickness-type response. The physiological significance of leptin's
      action on meningeal and endothelial cells remains to be clarified but might
      reflect a role in LPS-induced immune cell infiltration into the brain.

PMID- 18803241
TI  - Reinforcement of cell junctions correlates with the absence of hair cell
      regeneration in mammals and its occurrence in birds.
AB  - Debilitating hearing and balance deficits often arise through damage to the inner
      ear's hair cells. For humans and other mammals, such deficits are permanent, but
      nonmammalian vertebrates can quickly recover hearing and balance through their
      innate capacity to regenerate hair cells. The biological basis for this
      difference has remained unknown, but recent investigations in wounded balance
      epithelia have shown that proliferation follows cellular spreading at sites of
      injury. As mammalian ears mature during the first weeks after birth, the capacity
      for spreading and proliferation declines sharply. In seeking the basis for those
      declines, we investigated the circumferential bands of F-actin that bracket the
      apical junctions between supporting cells in the gravity-sensitive utricle. We
      found that those bands grow much thicker as mice and humans mature postnatally,
      whereas their counterparts in chickens remain thin from hatching through
      adulthood. When we cultured utricular epithelia from chickens, we found that
      cellular spreading and proliferation both continued at high levels, even in the
      epithelia from adults. In contrast, the substantial reinforcement of the
      circumferential F-actin bands in mammals coincides with the steep declines in
      cell spreading and production established in earlier experiments. We propose that
      the presence of thin F-actin bands at the junctions between avian supporting
      cells may contribute to the lifelong persistence of their capacity for shape
      change, cell proliferation, and hair cell replacement and that the postnatal
      reinforcement of the F-actin bands in maturing humans and other mammals may have
      an important role in limiting hair cell regeneration.

PMID- 18803242
TI  - Thalamocortical maturation in mice is influenced by body weight.
AB  - The emergence of the whisker-related patterning of the barrel cortex during the
      first postnatal week is a frequently assessed feature of rodent cortical
      development and has been used extensively to screen for effects of genetic
      mutations on neural development in mice. As alterations in body weight often
      accompany genetic mutations, we asked whether body weight itself might affect the
      progression of barrel cortex development in wildtype C57/BL6 mice. The body
      weight varied considerably between as well as within litters, and could differ by
      a factor of up to 1.6 between littermates. The establishment of the periphery
      related and barrel patterning was assessed at postnatal (P days) 4 and 6 using
      cytochrome oxidase and Nissl staining. We found that only 20% of the mouse pups
      had an established thalamocortical afferent pattern in the barrel cortex at P4 (4
      out of 21 brains), while the majority of the pups showed a well-established
      pattern at P6 (13 of 16 brains). At both ages the more developed barrel structure
      was found in the heavier littermates. Conversely, no periphery-related pattern
      was apparent in the somatosensory cortex at either P4 or P6 below a critical body
      weight of 2.6 g and 2.0 g, respectively. These findings may have implications for
      the interpretation of developmental changes in the barrel cortex of genetically
      modified mice.

PMID- 18803243
TI  - Conformational implications of an inversed pH-dependent antibody aggregation.
AB  - Antibody formulation development relies on accelerated stability data at elevated
      temperatures to optimize formulation parameters. However, the pH- and temperature
      dependence of aggregation is complicated for antibody formulations. In this
      study, a human monoclonal IgG2 antibody exhibited typical pH-dependent dimer
      formation under normal storage conditions (4 and/or 29 degrees C). However, an
      inversed pH-dependence was discovered for high molecular weight aggregate
      formation at elevated temperatures (37 degrees C). The different stability
      profiles exhibited at the various storage conditions resulted in nonlinearity of
      the Arrhenius kinetics. Thermal unfolding at or below 37 degrees C was not
      evident by differential scanning calorimetry. Enriched populations of the
      structural isoforms of the IgG2 subclass were tested for their unique temperature
      and pH-dependence of aggregation. The Arrhenius kinetics of aggregation for each
      of the individual IgG2 isoforms was also nonlinear. However, the temperature
      dependence of clipping suggested that clip-mediated aggregation was responsible
      for the increased higher order aggregates at low pH and elevated temperatures.
      Unique clip species resulting from the conformational differences between the
      IgG2 isoforms lead to increased aggregation. These results have implications on
      the mechanisms of antibody aggregation and on the validity of accelerated data to
      predict shelf-life accurately.

PMID- 18803244
TI  - Wnt/Frizzled family members mediate olfactory sensory neuron axon extension.
AB  - A comprehensive model has yet to emerge, but it seems likely that numerous
      mechanisms contribute to the specificity of olfactory sensory neuron (OSN) axon
      innervation of the olfactory bulb. Elsewhere in the nervous system the Wnt/Fz
      family has been implicated in patterning of anterior-posterior axes, cell type
      specification, cell proliferation, and axon guidance. Because of our work
      describing cadherin-catenin family member expression in the primary olfactory
      pathway, and because mechanisms of Wnt-Fz interactions can depend in part on
      catenins, we were encouraged to explore Wnt-Fz expression and function in OSN
      axon extension. Here, we show that OSNs express Fz-1, Fz-3, and Wnt-5a, whereas
      olfactory ensheathing cells (OECs) express Wnt-4. Fz-7 is also expressed in the
      olfactory nerve by cells that delineate large axon fascicles, but are negative
      for OEC markers. Fz-1 showed a developmental downregulation. However, in adults
      it is expressed at different levels across the olfactory epithelium and in
      restricted glomeruli across the olfactory bulb, suggesting an important role in
      the formation and maintenance of OSN connections to the olfactory bulb. Reporter
      TOPGAL mice demonstrated that some OECs located in the inner olfactory nerve
      layer can respond to Wnt ligands. Of further interest, we show here with in vitro
      assays that Wnt-5a increases OSN axon outgrowth and alters growth cone
      morphology. Our data point to a key role for Wnt/Fz molecules in the development
      of the mouse olfactory system, providing complementary mechanisms required for
      OSN axon extension and coalescence.

PMID- 18803245
TI  - Antioxidant activity of Sanionia uncinata, a polar moss species from King George
      Island, Antarctica.
AB  - Antioxidant agents counter reactive oxygen species (ROS) and can be used in
      cosmetic and medicinal applications. The goal of this study was to evaluate the
      antioxidant activity of an Antarctic moss species from King George Island
      (Antarctica), tentatively designated as KSJ-M5. On the basis of morphological
      characteristics, KSJ-M5 was identified as Sanionia uncinata (Hedw.) Loeske
      (Amblystegiaceae). The identification was confirmed by comparing the partial
      sequence of the ITS (internal transcribed spacer) region with that in GenBank.
      The antioxidant activity of an ethanol extract of KSJ-M5 was evaluated by
      analyzing its reducing power, superoxide scavenging activity, ABTS [2,2'-azino
      bis(3-ethylbenzthiazoline-6-sulphonic acid)] cation scavenging activity, and DPPH
      (1,1-diphenyl-2-picrylhydrazyl) free-radical scavenging activity. The reducing
      power of 1 mg of KSJ-M5 extract was equivalent to 31.9 +/- 0.9 microg (Mean +/-
      SD, n = 3) of the commercial standard, BHT (butylated hydroxytoluene). IC(50)
      values of the KSJ-M5 extract for DPPH free-radical scavenging activity,
      superoxide scavenging activity, and ABTS cation scavenging activity were found as
      356 +/- 26.8 microg/mL, 466.2 +/- 43.4 microg/mL, and 181.3 +/- 12.2 microg/mL,
      respectively. The total phenolic content in 1 mg of KSJM5 extract was equivalent
      to 12.7 +/- 2.7 microg of pyrocatechol. These results clearly showed that KSJ-M5
      could be an important source of natural antioxidant agents for improved medicinal
      and cosmetic applications.

PMID- 18803246
TI  - Preliminary investigation of the radiosensitizing activity of guduchi (Tinospora
      cordifolia) in tumor-bearing mice.
AB  - The radiosensitizing activity of dichloromethane extract of guduchi [Tinospora
      cordifolia (WILLD.) MIERS ex HOOK. F. & THOMS. Family: Menispermaceae (TCE)] in
      the mice transplanted with Ehrlich ascites carcinoma (EAC) was investigated. The
      EAC mice received 0, 25, 30, 40, 50 or 100 mg/kg b.wt. TCE 1 h before exposure to
      6 Gy hemi-body gamma-radiation and then once daily for another eight consecutive
      days after irradiation. The EAC mice receiving TCE for the above regimen showed a
      dose-dependent elevation in tumor-free survival; the highest radiosensitizing
      activity was observed at 30 mg/kg b. wt. TCE. Treatment of animals with 30 mg/kg
      b. wt. TCE, 1 h before exposure to 6 Gy of hemi-body gamma irradiation and
      subsequently once daily for another six consecutive days post-irradiation
      increased the life span of EAC mice. This is evident by more number of long-term
      survivors (LTS) as well as survivors beyond 120 days when compared to the group
      of animals that received TCE after irradiation for six consecutive days.
      Treatment modality was also altered to assess the radiosensitizing effect of TCE
      before and after irradiation. Evaluation of glutathione (GSH), glutathione S
      transferase (GST) and lipid peroxidation (LPx) in mice treated with TCE 1 h
      before irradiation and subsequently once daily for another six days showed a
      significant decline in GSH up to 14 h and GST up to 24 h accompanied by a
      significant elevation in LPx at 12 h post-irradiation. The radiosensitization of
      TCE may be due to depletion of glutathione and glutathione-S-transferase,
      accompanied by elevated levels of lipid peroxidation and DNA damage of tumor
      cells. Since Tinospora cordifolia is being used in India for treatment of various
      ailments, it may offer an alternative treatment strategy for cancer in
      combination with gamma radiation.

PMID- 18803247
TI  - GSM base stations: short-term effects on well-being.
AB  - The purpose of this study was to examine the effects of short-term GSM (Global
      System for Mobile Communications) cellular phone base station RF-EMF
      (radiofrequency electromagnetic fields) exposure on psychological symptoms (good
      mood, alertness, calmness) as measured by a standardized well-being
      questionnaire. Fifty-seven participants were selected and randomly assigned to
      one of three different exposure scenarios. Each of those scenarios subjected
      participants to five 50-min exposure sessions, with only the first four relevant
      for the study of psychological symptoms. Three exposure levels were created by
      shielding devices in a field laboratory, which could be installed or removed
      during the breaks between sessions such that double-blinded conditions prevailed.
      The overall median power flux densities were 5.2 microW/m(2) during "low," 153.6
      microW/m(2) during "medium," and 2126.8 microW/m(2) during "high" exposure
      sessions. For scenario HM and MH, the first and third sessions were "low"
      exposure. The second session was "high" and the fourth was "medium" in scenario
      HM; and vice versa for scenario MH. Scenario LL had four successive "low"
      exposure sessions constituting the reference condition. Participants in scenarios
      HM and MH (high and medium exposure) were significantly calmer during those
      sessions than participants in scenario LL (low exposure throughout) (P = 0.042).
      However, no significant differences between exposure scenarios in the "good mood"
      or "alertness" factors were obtained. We conclude that short-term exposure to GSM
      base station signals may have an impact on well-being by reducing psychological
      arousal.

PMID- 18803248
TI  - Effect of flavonoids on daunorubicin-induced toxicity in H9c2 Cardiomyoblasts.
AB  - Daunorubicin (DNR) is one of the most important antitumor agents belonging to the
      anthracycline group. However, its use is seriously limited by the development of
      cardiac toxicity. The present study was designed to investigate the effects of
      quercetin, pycnogenol and naringenin on daunorubicin-induced cytoxicity in H9c2
      cells. Protection of H9c2 cardiomyocyte cells was concentration/dose dependent
      for quercetin > naringenin > pycnogenol = trolox. Quercetin (10(-4)-10(-5) mol/L)
      after 24 h of co-incubation with DNR significantly increased the cardiomyocyte
      survival (p < 0.001 and p < 0.05, respectively). A protective effect of other
      compounds was observed only in the highest concentration/dose used (p < 0.01).
      After 48 h of incubation quercetin and naringenin significantly decreased
      daunorubicin-induced cell death at concentrations of 10(-4)-10(-5) mol/L (p <
      0.001 and p < 0.01, respectively). The protective effect of pycnogenol and trolox
      was weaker but significant in the two highest concentrations/doses (p < 0.001 and
      p < 0.05, respectively). This study also investigated DNR-induced apoptosis and
      it was shown that both quercetin and naringenin inhibit apoptosis of H9c2
      cardiomyocytes cells in vitro. The findings provide evidence that quercetin and
      naringenin may act as survival factors. The protective effect of flavonoids was
      compared with that of trolox, a known cardioprotective antioxidant. These results
      are consistent with the notion that the use of flavonoids may be beneficial in
      modulating or preventing the cardiotoxicity associated with DNR therapy.

PMID- 18803249
TI  - Effect of North American ginseng on 137Cs-induced micronuclei in human
      lymphocytes: a comparison with WR-1065.
AB  - To explore the radioprotective effect of a standardized North American ginseng
      extract (NAGE) on human peripheral blood lymphocytes (PBL), a micronuclei (MN)
      assay was conducted in PBL obtained from 12 volunteers. NAGE (50-1000 microg/mL)
      and WR-1065 (1 mM and 3 mM) were applied to PBL cultures at 0 h and 90 min post
      irradiation. It was found that (1) the baseline MN yield of PBL ranged from 14.4
      +/- 1.5 to 15.9 +/- 1.5 per 1000 binucleated cells (p > 0.05); after irradiation
      (1 Gy and 2 Gy), the MN yield increased sharply; (2) MN yields declined with
      increasing concentrations of NAGE and WR-1065. Even at 90 min post-irradiation of
      1 Gy, the maximum level of MN reduction rate caused by NAGE and WR-1065 was 53.8%
      and 59.2%, respectively; after 2 Gy irradiation, it was 37.3% and 42%,
      respectively; (3) the MN distribution in PBL followed a non-Poisson distribution
      in all cases; and (4) both NAGE and WR-1065 showed no significant effect on the
      proliferation index of lymphocytes. The results indicate that NAGE is a
      relatively non-toxic natural product, which can be administered as a dietary
      supplement and has the potential to be a radiation countermeasure.

PMID- 18803250
TI  - Citrus fruit flavonoids influence on neutrophil apoptosis and oxidative
      metabolism.
AB  - Citrus flavonoids are dietary antioxidants that may protect against oxidative
      stress linked to inflammation and reduce the risk of macromolecule damage caused
      by free radicals. Three citrus flavonoids - naringin, naringenin and hesperidin -
      have been examined for their ability to activate caspase-3, a marker of apoptosis
      execution, in human polymorphonuclear neutrophils in vitro, stimulated and non
      stimulated with phorbol 12-myristate 13-acetate. The flavonoid potency to reduce
      reactive oxygen species generation was also assessed in measurements of
      superoxide radical and luminol dependent chemiluminescence. The caspase-3
      activity depended on the time of flavonoid treatment and was increased markedly
      in phorbol-treated cells incubated with flavonoids for 24 h. Hesperidin at a
      concentration of 100 microm exerted the strongest stimulating effect on the
      enzyme (137% of control). Flavonoids inhibited the neutrophil ability to generate
      superoxide radical and 10-100 microM hesperidin appeared the most active
      phytochemical. The antioxidant capacity of the examined flavonoids was most
      prominently expressed in the chemiluminescent measurements. The obtained results
      suggest that reactive oxygen species may inhibit apoptosis via caspase-3
      inhibition and the antioxidant action of citrus flavonoids may reverse this
      process.

PMID- 18803251
TI  - Involvement of the Bcl-2 family members in Pinus massoniana bark extract induced
      apoptosis in HeLa cells.
AB  - Pinus massoniana bark extract (PMBE) contains a variety of flavonoids whose
      antioxidant properties have been confirmed in vitro. This study was undertaken to
      evaluate the cytotoxic effects and the mechanism of cell death on the PMBE
      treated human cervical cancer cell line, HeLa. PMBE treatment led to cell growth
      inhibition in a dose- and time-dependent manner, and PMBE-induced apoptosis was
      confirmed by DAPI staining, TUNEL assays and sub-G1 phase accumulation. Cell
      cycle was also arrested in G2/M phase. Immunoblotting analysis showed that
      cytochrome c was released, the protein expression of Bax was increased, the
      protein expression of Bcl-2 was down-regulated and caspase-9 and -3 were
      activated in PMBE-treated HeLa cells. Taken together, PMBE inhibited
      proliferation, induces apoptosis and causes cell cycle arrest in HeLa cells,
      indicating that PMBE may be a potential therapeutic agent for cancer.

PMID- 18803252
TI  - Space efficient system for whole-body exposure of unrestrained rats to 900 MHz
      electromagnetic fields.
AB  - The aim of this study was to design, implement and analyze a space-efficient
      setup for the whole-body exposure of unrestrained Wistar rats to radiofrequency
      (RF) electromagnetic fields at 900 MHz. The setup was used for 2 years in a
      cocarcinogenesis study and part of it for 5 weeks in a central nervous system
      (CNS) study. Up to 216 rats could be placed in separate cages in nine different
      exposure chambers on three racks requiring only 9 m2 of floor area (24 rats per
      m2). Chambers were radial transmission lines (RTL), where the rats could freely
      move in their cages where food and drinking water was provided ad libitum except
      during RF exposure periods. Dosimetrical analysis was based on FDTD computations
      with heterogeneous rat models and was validated with calorimetrical measurements
      carried out with homogeneous phantoms. The estimated whole-body average specific
      absorption rates (SAR) of rats were 0 (sham), 0.4, and 1.3 W/kg in the
      cocarcinogenesis study and 0 (sham), 0.27, and 2.7 W/kg in the CNS study with an
      estimated uncertainty of 3 dB (K = 2). The instantaneous and lifetime variations
      of whole-body average SAR due to the movement of rats were estimated to be 2.3
      and 1.3 dB (K = 1), respectively.

PMID- 18803253
TI  - Docosahexaenoic acid downregulates phenobarbital-induced cytochrome P450 2B1 gene
      expression in rat primary hepatocytes via the c-Jun NH2-terminal kinase mitogen
      activated protein kinase pathway.
AB  - Mitogen-activated protein kinase (MAPK) pathways play central roles in the
      transduction of extracellular stimuli into cells and the regulation of expression
      of numerous genes. Docosahexaenoic acid (DHA) was shown to be involved in the
      regulation of expression of drug metabolizing enzymes (DMEs) in rat primary
      hepatocytes in response to xenobiotics. Cytochrome P450 2B1 (CYP 2B1) is a DME
      that is dramatically induced by phenobarbital-type inducers. The constitutive
      androstane receptor (CAR) plays a critical role in regulating the expression of
      DMEs, and the phosphorylation/dephosphorylation of CAR is an important event in
      CYP 2B1 expression. In the present study, we determined the effect of DHA on MAPK
      transactivation and its role in CYP 2B1 expression induced by phenobarbital. c
      Jun NH2-terminal kinase (JNK) JNK1/2 and ERK1/2 were activated by phenobarbital
      in a dose-dependent manner. DHA (100 muM) inhibited JNK1/2 and ERK2 activation
      induced by phenobarbital in a time-dependent manner. Both SP600125 (a JNK
      inhibitor) and SB203580 (a p38 MAPK inhibitor) inhibited CYP 2B1 protein and mRNA
      expression induced by phenobarbital. SB203580 significantly increased the
      intracellular 3'-5'-cyclic adenosine monophosphate (cAMP) concentration compared
      with a control group (p < 0.05). Our results suggest that inhibition of JNK
      activation by DHA is at least part of the mechanisms of DHA's downregulation of
      CYP 2B1 expression induced by phenobarbital.

PMID- 18803254
TI  - Determination of radix ginseng volatile oils at different ages by comprehensive
      two-dimensional gas chromatography/time-of-flight mass spectrometry.
AB  - Comprehensive 2-D GC (GC x GC) coupled with TOF MS or flame ionization detector
      (FID) was employed to characterize and quantify the chemical composition of
      volatile oil in the radixes of Panax ginseng C. A. Mey. (ginseng) at different
      ages. Thirty-six terpenoids were tentatively identified based on the MS library
      search and retention index in a ginseng sample at the age of 3 years. An obvious
      group-type separation was obtained in the GC x GC-TOF MS chromatogram. The data
      collected by GC x GC-FID were processed using a principal component analysis
      (PCA) method to classify the samples at different ages. The compounds responsible
      for the significant differentiation among samples were defined. It was found that
      the relative abundances of alpha-cadinol, alpha-bisabolol, thujopsene, and n
      hexadecanoic acid significantly rise with the increase in age.

PMID- 18803255
TI  - Comprehensive two-dimensional gas chromatography analysis of high-ethanol
      containing motor fuels.
AB  - A comprehensive 2-D GC (GC x GC) instrument equipped with a flow-switching
      modulator was used to determine the concentration of ethanol and eight other
      alcohols in a retail pump sample of E85 fuel. E85 is a mixture of ethanol and
      gasoline where the ethanol concentration can range from 70 to 85 vol%. The
      increased peak capacity and selectivity generated by GC x GC analysis allowed the
      alcohols to be fully resolved from the gasoline hydrocarbons. GC x GC analysis
      was compared to the performance obtained with the standard analytical method for
      determining ethanol in fuel ethanol (ASTM D5501) and the standard method for
      determining oxygenate concentrations in gasoline (ASTM D4815). The GC x GC
      analysis required 14 min while the combined ASTM D5501 and ASTM D4815 analyses
      required more than 60 min. The ethanol concentration obtained by GC x GC was in
      excellent agreement with the value obtained by the D5501 method. Poorer agreement
      was observed between the GC x GC and D4815 concentrations for the other alcohols
      present in E85. In all cases, the differences could be attributed to deficiencies
      in the D4815 method that led to coelutions between the alcohols and gasoline
      hydrocarbons.

PMID- 18803256
TI  - Column selection for comprehensive multidimensional ion chromatography.
AB  - This paper discusses the selection of ion chromatography (IC) columns for use in
      comprehensive multidimensional ion chromatography (IC x IC). First, a single
      number was determined for a wide range of anions (one number for each anion)
      using the linear solvent strength model. These numbers were then used to compare
      the column selectivity characteristics for five different columns. Principal
      component analysis was used to illustrate selectivity differences between
      columns. Dionex AS16 and AS20 columns were selected for use in the development of
      an IC x IC method for the separation of ten anions. To achieve the required speed
      of analysis in both the first and second separation dimensions, custom column
      lengths were packed in-house. The use of an eluent suppressor between the first
      and second columns permits a relatively low flow ratio regime of only <1:20 in
      the first and second dimensions, respectively, which reduces dilution effects
      common in comprehensive multidimensional LC. Selection of the second dimension
      eluent conditions was aided by the development of a spreadsheet based on the
      linear solvent strength model.

PMID- 18803257
TI  - Antibiotics, arsenate and H2O2 induce the promoter of Staphylococcus aureus cspC
      gene more strongly than cold.
AB  - Proteins expressed by the bacterial cold shock genes are highly conserved at
      sequence level and perform various biological functions in both the cold-stressed
      and normal cells. To study the effects of various agents on the cold shock genes
      of Staphylococcus aureus, we have cloned the upstream region of cspC from S.
      aureus Newman and found that the above region possesses appreciable promoter
      (P(c)) activity even at 37 degrees C. A reporter S. aureus strain CHANDA2,
      constructed by inserting the P(c)-lacZ transcriptional fusion into S. aureus
      RN4220 genome, was found to express very low level of beta-galactosidase after
      cold shock, indicating that low temperature induces P(c) very weakly.
      Interestingly, transcription from P(c ) was induced very strongly by several
      antibiotics, hydrogen peroxide and arsenate salt. Cold shock proteins expressed
      by S. aureus are highly identical at sequence level and bear single-strand
      nucleic acid binding motifs. A 16 nt downstream box and a 13 nt upstream box were
      identified at the downstream of initiation codon and at the upstream of ribosome
      binding site of csp transcripts. Their roles in S. aureus cold shock gene
      expression have been discussed elaborately.

PMID- 18803258
TI  - No carry over of unmetabolised deoxynivalenol in milk of dairy cows fed high
      concentrate proportions.
AB  - To examine the carry over of deoxynivalenol (DON) and its metabolite de-epoxy DON
      (DOM-1) in milk, lactating German Holstein cows (n = 13) were fed an isoenergetic
      total mixed ration in Period 1 with 50% concentrates and 5.3 mg DON/kg dry matter
      (DM) over 11 wk and were compared with control cows (n = 14). In Period 2 (18
      wk), an elevated concentrate proportion was compared to a low concentrate ration
      by dividing the cows into four Groups (n = 8): Control-30 (30% concentrates),
      Myco-30 (30% concentrates, 4.4 mg DON/kg DM), Control-60 (60% concentrates) and
      Myco-60 (60% concentrates, 4.6 mg DON/kg DM). Taken both periods together, no
      unmetabolised DON was detected in milk samples using the HPLC-UV method. DOM-1
      concentrations ranged between below the LOD and 3.2 microg/kg milk in mycotoxin
      fed cows, while control cows did not excrete any measurable amounts of DOM-1.
      Regarding the concentrate effects, the carry over of DON as DOM-1 in milk was
      negligible (between 0.0001 and 0.0011) but significantly higher in Group Myco-30
      than in Group Myco-60. This effect may result from an altered bioavailability of
      DON from maize silage which made up a higher proportion of the daily ration.

PMID- 18803259
TI  - Do intrinsic factor antibodies assays provide univocal answers in Biermer's
      disease?
AB  - The objective of the study is to evaluate the concordance of four assays for
      antibodies against intrinsic factor (IF-Ab). Sixty-two sera were tested with one
      competitive automated and three manual noncompetitive assays. Thirty-five percent
      patients had discordant results with at least one of the four assays. However,
      any method uncovered patients with proven Biermer's disease missed by the others
      assays. The observed discordance partly explains the poor sensitivity of IF-Ab in
      studies using a single assay.

PMID- 18803260
TI  - Polymorphism and solvatomorphism 2007.
AB  - Papers and patents that deal with polymorphism (crystal systems for which a
      substance can exist in structures characterized by different unit cells, but
      where each of the forms has exactly the same elemental composition) and
      solvatomorphism (systems where the crystal structures of the substance are
      defined by different unit cells, but where these unit cells differ in their
      elemental composition through the inclusion of one or molecules of solvent) have
      been summarized in an annual review. The works cited in this review were
      published during 2007, and were drawn from the major physical, crystallographic,
      and pharmaceutical journals. The review is divided into sections that cover
      articles of general interest, computational and theoretical studies, preparative
      and isolation methods, structural characterization and properties of polymorphic
      and solvatomorphic systems, studies of phase transformations, effects associated
      with secondary processing, and United States patents issued during 2007.

PMID- 18803261
TI  - Novel mucoadhesive extended release tablets for treatment of oral candidosis: "in
      vivo" evaluation of the biopharmaceutical performance.
AB  - Mucoadhesive tablets containing nystatin (10 mg) were evaluated in vivo. The
      assays were carried out with 12 healthy volunteers and the concentration of
      nystatin in saliva was determined at different times. Tablets remained attached
      to the buccal mucosa during 270 min +/- 30 min. No evidence of ulceration or
      bleeding was observed. Typical appearance of intact human buccal mucosa was seen
      before and after contact with the tablet. The tablets were well accepted by the
      volunteers, although most of the volunteers reported a light bitter taste,
      probably due to nystatin. Concentration of nystatin in saliva was several times
      higher than MIC over a period of approximately 4.5 h, which was in agreement with
      the behavior observed in vitro. These results allow us to infer that the
      administration of these mucoadhesive tablets could be advantageous compared to
      conventional formulations and mucoadhesive extended-release tablets might produce
      better therapeutic performance than conventional formulations in the treatment of
      oral candidosis.

PMID- 18803262
TI  - Efficient telomerase inhibition in human non-small cell lung cancer cells by
      liposomal delivery of 2'-O-methyl-RNA.
AB  - The antisense oligonucleotide 2'-O-methyl-RNA is a selective telomerase inhibitor
      targeting the telomerase RNA component and represents a potential candidate for
      anticancer therapy. The poor cellular uptake of 2'-O-methyl-RNA is a limiting
      factor that may contribute to the lack of functional efficacy. To improve
      delivery of 2'-O-methyl-RNA and consequently antitumoral efficiency in human lung
      cancer cells, we have investigated several transfection reagents. The
      transfection reagents DOTAP, MegaFectin 60, SuperFect, FuGENE 6 and MATra-A were
      tested for intracellular delivery. A FAM-labeled 2'-O-methyl-RNA was used to
      assess the intracellular distribution by confocal laser scanning microscopy in
      A549 human non-small cell lung cancer cells. Telomerase activity was measured
      using the telomeric repeat amplification protocol. Cell viability after
      transfection was quantified by the MTT assay. All transfection reagents enhanced
      2'-O-methyl-RNA uptake in A549 cells but the cationic lipid reagents DOTAP and
      MegaFectin 60 were most efficient in the delivery of 2'-O-methyl-RNA resulting in
      telomerase inhibition. Among both DOTAP exhibited the lowest cytotoxicity. Our
      experiments show that DOTAP is the most suitable transfection reagent for the
      delivery of 2'-O-methyl-RNA in human lung cancer cells according to its
      relatively low cytotoxicity and its ability to promote efficient uptake leading
      to the inhibition of telomerase.

PMID- 18803263
TI  - Improved pharmacokinetic and bioavailability support of drug discovery using
      serial blood sampling in mice.
AB  - Pharmacokinetic studies in mice traditionally require one animal per time point,
      resulting in dosing and euthanizing a large number of animals and producing
      suboptimal quality of pharmacokinetic data due to inter-animal variability and
      dosing error. These studies are time-consuming and labor-intensive. To improve
      the throughput and quality of pharmacokinetic evaluation in mice, we have
      developed a serial blood sampling methodology using the lateral saphenous vein
      puncture technique. Two marketed drugs, indinavir and rosuvastatin, were selected
      for this validation study because of their distinctly different physicochemical
      and pharmacokinetic properties. Each compound was dosed orally and intravenously
      in mice using both discrete and serial blood sampling methods. The
      pharmacokinetic results from serial bleeding are in excellent agreement with
      those from discrete sampling for both compounds. Compared to the discrete
      sampling, the serial sampling procedure is a more humane method, allowing for
      rapid and repeated sampling from the same site without the need for anesthesia.
      The application of this new method has led to a remarkable reduction in animal
      and compound usage, a significant increase in throughput and speed, and a drastic
      improvement in pharmacokinetic data quality. This approach is especially useful
      for the first-tier in vivo pharmacokinetic screening of discovery compounds.

PMID- 18803264
TI  - A combined pharmacokinetic-pharmacodynamic (PK-PD) model for tumor growth in the
      rat with UFT administration.
AB  - A combined pharmacokinetic-pharmacodynamic model was developed to simulate the
      response of a rat tumor to UFT, a combination of uracil with Tegafur (FT).
      Tegafur is oral the prodrug of 5-fluorouracil (5-FU), an anti-cancer drug for
      colon cancer. A physiologically based pharmacokinetic (PBPK) model was developed
      and fitted to experimental data from literature. Three pharmacodynamic (PD)
      models were developed to describe the tumor cell growth treated with 5-FU, and a
      dual transit compartment model gave the best fit. This result may be due to dual
      mechanisms of action of 5-FU, and the dual transit compartment model is able to
      simulate these better than the other models. The PBPK and PD models were
      combined, and various dosing strategies were tested. The optimal ratio of uracil
      to Tegafur to maximize tumor reduction and minimize systemic toxicity was found
      to be consistent with previous reports. The model correctly predicted the toxic
      effect of low dihydropyrimidine dehydrogenase (DPD) level, consistent with
      clinical tests. Pharmacokinetic modulating chemotherapy (PMC), which combines
      continuous infusion of 5-FU and periodic administration of UFT was shown to be
      more effective than the same dose given by continuous infusion only. This model
      can guide the development of dosing strategies and patient specific 5-FU
      therapies.

PMID- 18803265
TI  - A screening study of surface stabilization during the production of drug
      nanocrystals.
AB  - In order to establish a knowledge base for nanosuspension production, a screening
      was performed on 13 different stabilizers at 3 concentrations for 9 structurally
      different drug compounds. Concerning the stabilizers tested, the group of semi
      synthetic polymers was the least performant (stable nanosuspensions were obtained
      in only 1 out of 10 cases). For the linear synthetic polymers, better results
      were obtained with povidones, however poly(vinyl alcohol) did not result in
      adequate stabilization. The synthetic copolymers showed even higher success
      rates, resulting in nanosuspensions in two out of three cases when applied at a
      100 wt% concentration (relative to the drug weight). Finally, the surfactants
      gave the best results, with TPGS being successful at concentrations of 25 or 100
      wt% of the drug weight for all compounds tested. From the point of view of drug
      compound, large differences could be observed upon evaluation of the relative
      number of formulations of that compound resulting in nanosuspensions. It was
      found that the hydrophobicity of the surfaces, as estimated by the adsorbed
      amount of TPGS per unit of surface area of nanosuspensions stabilized with 25 wt%
      TPGS, was decisive for the agglomeration tendency of the particles and hence the
      ease of nanosuspensions stabilization.

PMID- 18803266
TI  - p53 codon 72 proline/arginine polymorphism and autoimmune thyroid diseases.
AB  - p53 protein participates in the processes of apoptosis, which is involved in a
      number of immunological reactions. In order to test whether the p53 gene could be
      used as a genetic marker for the prediction of the development of autoimmune
      thyroid diseases (AITD), we screened, by using polymerase chain reaction (PCR)
      analysis, for the C (CCC)/G (CGC) polymorphism at the p53 codon 72 (Pro 72/Arg
      72) to determine the genotypes of 107 Hashimoto's thyroiditis (HT) and 90 Graves'
      disease (GD) patients, and 105 normal controls. The data demonstrated that, for
      the genotype analysis, HT patients featured an enhanced numerical ratio for the
      Arg/Arg homozygous genotype (33.7%) and a diminished ratio for the Arg/Pro
      heterozygous genotype (41.1%) at the p53 codon 72 than was the case for normal
      controls (Arg/Arg: 17.1% and Arg/Pro: 61.9%; P=0.005). The odds ratio for the
      risk of the Arg/Arg genotype's appearance, compared with that of the Arg/Pro and
      Pro/Pro genotypes combined, for the HT patient group was 2.450 (95% confidence
      interval: 1.274-4.716). With respect to allelic analysis, we did not observe
      significant difference in the frequency of appearance of the Arg allelic variant
      and the Pro allelic variant for the p53 codon 72 when comparing the HT patient
      group with the control group (P=0.208). On the other hand, GD patients presented
      no significant difference in distribution for both genotype and allelic
      frequencies (P=0.344 and 0.245, respectively) when compared with normal controls.
      In conclusion, HT patients feature a greater ratio of arginine homozygosity at
      p53 codon 72 than in the case for normal subjects. The p53 codon 72
      proline/arginine polymorphism may be a genetic marker to predict the increased
      susceptibility of development of HT.

PMID- 18803267
TI  - Coeliac disease screening in children: assessment of a novel anti-gliadin
      antibody assay.
AB  - Coeliac disease (CD) screening has progressed rapidly with tissue
      transglutaminase (TTG), the screening tool of choice. However, TTG may be
      unreliable in young children and advances in CD etiology understanding have seen
      improvements in anti-gliadin (AGA) assay technology. The aim of this study was to
      investigate the utility of an updated and refined AGA (Neogliadin) assay for CD
      screening in children with gastrointestinal symptoms. Children attending the
      Sydney Children's Hospital, Randwick, with gastrointestinal symptoms had sera
      collected and assayed by Neogliadin and commercial TTG assays in addition to the
      usual clinical work-up. One hundred and fifteen children were recruited in which
      32 were diagnosed with CD. AGA-IgA screening by Neogliadin showed improved
      sensitivity (83%) and specificity (91%) but did not eclipse the sensitivity (93%)
      and specificity (90%) of TTG-IgA screening. In the children diagnosed with CD, 7
      were identified as younger than 5 years of age with 4/7 AGA-IgA positive, 5/7 AGA
      IgG positive, and 6/7 TTG-IgA positive. The updated Neogliadin IgA assay does not
      improve on the accuracy achieved by TTG screening. TTG appears to be a suitable
      screening tool for children younger than 5 years of age although this preliminary
      finding requires confirmation.

PMID- 18803268
TI  - Improved diagnoses of autoimmune hepatitis using an anti-actin ELISA.
AB  - The presence of antismooth muscle antibodies is one of the diagnostic criteria of
      autoimmune hepatitis. We evaluated a new anti-F-actin ELISA test and compared it
      with indirect immunofluorescence assay (IIFA) for antismooth muscle antibodies
      (ASMA). Two hundred and nine serum samples (35 autoimmune hepatitis, 174 other
      hepatopathies and control sera) were tested by IIFA on mouse stomach kidney
      sections for ASMA and by the Quanta Lite Actin ELISA for anti-F-actin antibodies.
      ASMA were detected in 26 of 35 sera from autoimmune hepatitis (74%) as compared
      with 25 (71%) with anti-actin antibodies, as well as in 25 of 49 (51%) samples
      from viral hepatitis as compared with 7 (14%) with anti-actin antibodies. With
      regards to autoimmune hepatitis, though sensitivity (74.3 vs 71.4%) and negative
      predictive value (93.5 vs 93.9%) of ASMA and anti-actin ELISA were comparable,
      anti-actin ELISA was significantly better than ASMA IIFA in terms of specificity
      (89.7 vs 74.7%), and positive predictive value (58.1 vs 37.1%). Although
      frequently positive in HCV samples, a comparable sensitivity but better
      specificity makes the anti-actin ELISA a useful tool in combination with ASMA
      IIFA for the screening and diagnosis of autoimmune hepatitis.

PMID- 18803269
TI  - Three-way comparison of methods for the measurement of the erythrocyte
      sedimentation rate.
AB  - An erythrocyte sedimentation rate (ESR) is a nonspecific sickness index, which is
      not diagnostic of any particular disease, but which when elevated may indicate
      the presence of inflammation, infection, rheumatologic disease, or neoplasm.
      Technological advances continue to evolve to make this old test to conform to
      requirements of a modern analytical laboratory. In this evaluation, two new semi
      automated ESR measuring systems, the HumaSed and ESR-Auto Plus (EAP), were
      compared with the Westergren method with regard to the accuracy and precision of
      ESR measurement, sample stability, and interference of various substances with
      the ESR assay. Samples from 125 patients were analyzed with the three methods and
      the results compared using linear regression and Bland-Altman plots. The mean ESR
      values of the HumaSed (32.10+/-4.86) and EAP (38.09+/-5.33) were comparable to
      that of the Westergren (31.54+/-4.94). The high correlation coefficients of 0.910
      0.96 and the Bland-Altman scatter plots revealed good association and agreement
      between the three methods. Bias between the three methods was small and the
      imprecision was within acceptable limits. ESR analysis beyond 4 hr was found to
      be unacceptable owing to sample instability. There was bilirubin and lipid but
      not heparin interference in the two automated systems. Overall, two automated
      analyzers were found to be fast, reliable, standardized, simplified, and safe
      instruments with accuracy and precision for ESR measurement comparable to the
      Westergren.

PMID- 18803270
TI  - Normal blood cells reference intervals of healthy adults at the Gaza Strip
      Palestine.
AB  - Hematological parameters are affected by different factors that include age, sex,
      smoking, ethnicity, and environmental altitude. It has been justified that each
      population must establish its own normal reference intervals to be used in
      clinical assessments and interpretations. Hematological reference intervals for
      adults from the Gaza Strip-Palestine have never been addressed. Therefore, this
      study was designed and aimed at the establishment of normal blood cells reference
      intervals for healthy adults at the Gaza Strip-Palestine. This study involved
      89,491 apparently healthy individuals (from both sexes and from the different
      governorates of the Gaza Strip) who were referred to the Thalassemia Central
      Laboratory during the period from September 2000 until February 2008. Complete
      blood counts were performed. Subjects were categorized into subgroups according
      to gender, smoking habit, and age (15-18, 19-45, and >45 years old). For each
      subgroup, descriptive and comparative statistical analysis was performed for
      hematological parameters. The results showed substantial differences between
      males and females, between smokers and nonsmokers, and between the different age
      groups. Moreover, reference intervals derived from our population are markedly
      shifted downward as compared with Western European and American populations. It
      was concluded that separate and region-specific reference intervals based on
      gender, smoking, and age for the Palestinian population at the Gaza Strip should
      be generalized for clinical laboratories and clinical practitioners, which could
      help in interpreting laboratory hematological tests more specifically, and
      potentially develop the quality of medical care provided to patients.

PMID- 18803271
TI  - Comparative evaluation of FASTPlaque assay with PCR and other conventional in
      vitro diagnostic methods for the early detection of pulmonary tuberculosis.
AB  - Rapid and accurate diagnosis of symptomatic patients of pulmonary tuberculosis
      (TB) is highly desirable to minimize the spread of the disease in the society.
      We, therefore, compared the usefulness of various conventional diagnostic
      methods, the in-house polymerase chain reaction (PCR), and the FASTPlaque assay
      in this study. Laboratory data of 150 patients with clinical diagnosis of
      pulmonary TB and 50 controls were included in this study. The sputa from all
      these 200 individuals were subjected to acid-fast staining, culture on Lowenstein
      Jensen (L-J) slants, automated BACTEC-MGIT-960 culture methods, and a
      mycobacteriophage assay. A mycobacterium genus and Mycobacterium tuberculosis
      species-specific PCRs were also done and samples positive on both PCRs were
      considered as standard for comparison. Of the 5 in vitro diagnostic tests, PCR
      method was found to be the most rapid, sensitive, and specific, detecting all the
      150 cases of pulmonary TB without any false-positive and negative result. In
      comparison with PCR the sensitivity of MGIT-960 was 90%, followed by FASTPlaque
      assay (76.7%), L-J culture method (73.3%), and microscopy (60%). The mean
      detection time for smear-positive and smear-negative samples was 12.5 and 14 days
      in MGIT-960 and 18 and 25 days for L-J method, respectively. The FASTPlaque
      failed to detect mycobacteria from the paucibacillary samples. The contamination
      rates for MGIT-960, L-J, and FASTPlaque assays were 4, 8 and 10%, respectively.
      The best correlation with mycobacterial load in the specimen was observed in
      BACTEC-MGIT-960 showing 66.6% detection rate in paucibacillary, 83.3% in 1+
      samples, and 100% in 2+ and 3+ samples. Out of the 150 patients, 140 (93.3%)
      could be diagnosed by one or more nonmolecular methods. Therefore, it could be
      concluded that combination of three or more in vitro diagnostic methods will have
      acceptable detection level.

PMID- 18803272
TI  - Evaluation of a new commercial enzyme immunoassay for the detection of IgM
      antibodies to West Nile virus using a ratio method to eliminate nonspecific
      reactivity.
AB  - As West Nile virus (WNV) has become endemic in the United States, following the
      first reported cases in New York during the summer of 1999, the demand for
      specific serology has increased. Several IgM capture ELISA assays for the
      detection of WNV-specific IgM have been approved by the Food and Drug
      Administration for in vitro diagnostic testing, including kits from Focus
      Diagnostics and InBios International, Inc. The Focus Diagnostics IgM capture
      ELISA has a background subtraction protocol and the InBios IgM capture ELISA
      implements a ratio method to detect nonspecific reactivity due to rheumatoid
      factor, heterophile antibodies, and other interfering substances. We compared the
      InBios IgM capture ELISA with the Focus Diagnostics capture ELISA. Agreement,
      sensitivity, and specificity of the InBios IgM capture ELISA were 99, 98, and
      100%, respectively. Samples that originally tested positive on the Focus
      Diagnostics IgM capture ELISA without the subtraction protocol and were then
      determined negative following the subtraction protocol agreed 100% with the
      InBios IgM capture ELISA. We conclude that a method to eliminate background
      reactivity is a necessary portion of any anti-WNV IgM assay in order to eliminate
      false-positive results.

PMID- 18803273
TI  - Use of vaginal pH in diagnosis of infections and its association with
      reproductive manifestations.
AB  - Increase in vaginal secretion pH is an indicator of bacterial vaginosis (BV), but
      is yet to be in use as a diagnostic tool by clinicians. Similarly, no reports are
      available on the effect of cervical chlamydia infection and different
      reproductive manifestations on vaginal secretion pH. This study evaluated the use
      of vaginal pH for screening of BV, the effect of Chlamydia trachomatis (C.
      trachomatis) infection, and different reproductive manifestations on vaginal pH
      of women attending the gynecology outpatient department of a general hospital.
      Vaginal pH was recorded while diagnosing infections in 358 women, among which 45
      were with repeated spontaneous abortion, 79 with infertility, 185 had sign and
      symptoms of lower genital tract infection, and 49 had no history or symptom of
      any complications or infections. Normal vaginal pH, BV, and C. trachomatis
      infection were observed in 72.6, 21.5, and 10.1% of women, respectively. BV and
      C. trachomatis were observed in 78.6 and 4.1% of women, respectively, with high
      vaginal pH; 12.3% of women with normal vaginal pH had C. trachomatis infection.
      C. trachomatis infection or different reproductive manifestations do not lead to
      change in vaginal pH but high vaginal pH correlated with BV and should be used as
      a simple tool for its diagnosis.

PMID- 18803274
TI  - Serum adipocyte-fatty acid binding protein discriminates patients with permanent
      and temporary body weight loss.
AB  - Adipocyte-fatty acid binding protein (A-FABP) is a biomarker of adiposity and
      metabolic syndrome. The aim of our work was to investigate the effect of weight
      reduction on serum A-FABP value. In the study, we analyzed a group of 189
      probands suffering from obesity (102 women and 87 men; aged 57.3+/-12 years)
      initially, after a 3-month low-fat diet and once again 3 months after the
      termination of the diet for serum A-FABP, insulin, glucose, total cholesterol,
      HDL-cholesterol, LDL-cholesterol, and triglycerides. Basal biomarker
      concentrations were typical of the metabolic syndrome, and moreover A-FABP
      correlated with Quicki and BMI. We observed a reduction in BMI in 145 subjects
      who were divided into two subgroups: A-with persistent BMI reduction even after 6
      months, B-with BMI reduction after 3 months and its regress after 6 months.
      Individuals with rise or no BMI difference were signed as subgroup C. In subgroup
      A, A-FABP level increased and returned to the earlier level (42.3 vs 68.3 vs 37.1
      microg/l) and correlated with the markers of the metabolic syndrome. In subgroup
      B, A-FABP level increased less significantly, however elevated A-FABP level
      persisted for 6 months (41.9 vs 53.6 vs 50.7 microg/l). Subgroup C (n=54) showed
      no difference in A-FABP after 3-month diet and after next 3 months. The A-FABP
      value correlated with the some components of the metabolic syndrome. In
      conclusion, we describe that serum A-FABP might be a prognostic marker of body
      weight loss suggesting a preventive therapeutic intervention.

PMID- 18803275
TI  - DNA hydration studied by pressure perturbation scanning microcalorimetry.
AB  - Pressure perturbation differential scanning calorimetry was used to determine
      thermal expansion coefficients and thus temperature-induced volume changes of DNA
      duplexes differing in their GC/AT content. It was shown that the temperature
      induced unfolding of the DNA duplexes proceeds with a significant increase of the
      thermal expansion coefficient and the partial volume of the DNA. Unusually, large
      temperature-induced changes in the partial volume were observed for an AT-rich
      dodecamer, a finding consistent with previous crystallographic studies showing
      the presence of highly ordered water molecules hydrating the minor groove of such
      duplexes. The data show that the density of this ordered water is substantially
      higher than that of the bulk water. This ordered water cannot, therefore, be
      equated to ice at normal pressures but it thermodynamically resembles ice formed
      at high pressures.

PMID- 18803276
TI  - Pleural fluid findings as prognostic factors for malignant pleural mesothelioma.
AB  - The aim of this study was to determine the prognostic value of pleural fluid
      glucose, lactate dehydrogenase (LDH), albumin, total protein, and total leukocyte
      levels in patients with malignant pleural mesothelioma. We retrospectively
      analyzed 71 consecutive patients (33 men and 38 women) who were referred to the
      department of chest diseases in a university hospital. Pleural fluid glucose
      levels, the ratio of pleural fluid to serum LDH>1.0, and total leukocyte count
      were significant predictors for the survival in univariate analysis. However,
      none of these variables emerged as statistically significant from the
      multivariate Cox model. In conclusion, our results showed that there is an
      inverse correlation between the intensity of inflammation and survival.

PMID- 18803277
TI  - A case report of secondary autograft failure due to Gaucher disease.

PMID- 18803278
TI  - Delayed-onset HIT caused by low-molecular-weight heparin manifesting during
      fondaparinux prophylaxis.
AB  - Heparin-induced thrombocytopenia (HIT) is a prothrombotic condition caused by
      platelet-activating antibodies that react with platelet factor 4 (PF4)/heparin
      complexes. Delayed-onset HIT occurs after heparin is stopped. Fondaparinux, a
      synthetic pentasaccharide, is thought to be a safe alternative anticoagulant in
      HIT. We describe a patient with delayed-onset HIT triggered by low-molecular
      weight heparin (LMWH) which occurred during fondaparinux prophylaxis and which
      was complicated by microangiopathic hemolytic anemia. Patient serum contained
      high-titer anti-PF4/heparin antibodies demonstrating heparin-dependent platelet
      activation with serial dilutions. Confirmed delayed-onset HIT with LMWH has not
      been previously reported. Low dose fondaparinux does not necessarily prevent
      thrombotic complications of HIT.

PMID- 18803279
TI  - Immunophenotypic profile of acute leukemia: critical analysis and insights gained
      at a tertiary care center in India.
AB  - BACKGROUND: To analyze the spectrum of various types and subtypes of acute
      leukemia. METHODS: Two thousand five hundred and eleven consecutive new referral
      cases of acute leukemia (AL) were evaluated based on WHO classification. RESULTS:
      It included 1,471 cases (58%) of acute lymphoblastic leukemia (ALL), 964 cases
      (38%) of acute myeloid leukemia (AML), 45 cases (1.8%) of chronic myelogenous
      leukemia in blast crisis (CMLBC), 37 cases (1.5%) of biphenotypic acute leukemia
      (BAL), 1 case of Triphenotypic AL, and 2 cases of acute undifferentiated leukemia
      (AUL). Common subtypes of ALL were B-cell ALL (76%), which comprised of
      intermediate stage/CALLA positive (73%), early precursor/proBALL (3%). T-cell ALL
      constituted 24% (351 cases) of ALL. Common subtypes of AML included AMLM2 (27%),
      AMLM5 (15%), AMLM0 (12%), AMLM1 (12%), APML (11%), and AML t(8;21) (9%). CMLBC
      was commonly of myeloid blast crisis subtype (40 cases). CONCLUSION: B-cell ALL
      was the commonest subtype in children and AML in adults. Overall incidence of AML
      in adults was low (53% only). CD13 was most sensitive and CD117 most specific for
      determining myeloid lineage. A minimal primary panel of nine antibodies
      consisting of three myeloid markers (CD13, CD33, and CD117), B-cell lymphoid
      marker (CD19), T-cell marker (CD7), with CD45, CD10, CD34, and HLADR could assign
      lineage to 92% of AL. Cytogenetics findings lead to a change in the diagnostic
      subtype of myeloid malignancy in 38 (1.5%) cases.

PMID- 18803280
TI  - Flow cytometric quantitation of natural killer cells and T lymphocytes expressing
      T-cell receptors alpha/beta and gamma/delta is not helpful in distinguishing
      benign from malignant body cavity effusions.
AB  - BACKGROUND: Quantitation of natural killer (NK) cells in benign and malignant
      effusions has yielded conflicting results in the past. Studies have claimed
      higher, lower, and essentially equal percentages of NK cells for benign and
      malignant effusions. In addition, virtually no literature exists on the numbers
      and distribution of T lymphocytes expressing T-cell receptor alpha/beta (TCR
      alpha/beta) and T-cell receptor gamma/delta (TCR gamma/delta) in body effusions.
      METHODS: Using multicolor flow cytometry and sequential gating techniques, NK
      cells and T lymphocytes expressing TCR alpha/beta and TCR gamma/delta were
      identified and quantitated in 30 benign and 30 malignant effusions. RESULTS: No
      significant difference in percentage of NK cells was found between benign and
      malignant effusions. The absolute number per miroliter of CD16(+)CD56(+) NK cells
      was higher in malignant than in benign effusions, but only at a borderline level
      of statistical significance. T cells expressing TCR alpha/beta far outnumbered
      those expressing TCR gamma/delta in all effusions, a distribution similar to that
      in normal adult peripheral blood and lymphoid tissue. The percentages and
      absolute numbers of these T-cell subsets were the same in benign and malignant
      effusions. CONCLUSIONS: Enumeration of NK cells and of T lymphocytes expressing
      TCR alpha/beta or TCR gamma/delta in human body effusions is not helpful in
      attempting to distinguish between benign and malignant effusions. Values for the
      two T-lymphocyte subsets in human effusions are, to our knowledge, established
      for the first time by flow cytometric determination.

PMID- 18803281
TI  - Reduced anxiety in the mice expressing mutant (N141I) presenilin 2.
AB  - Alzheimer's disease (AD) is characterized by progressive cognitive impairment.
      The effect of presenilin 1 (PS1) and PS2 mutation on cognition has been well
      characterized in a variety of transgenic mice. However, noncognitive behaviors
      have not been considered in these mice. In the present study, we found that
      transgenic mice expressing mutant PS2 (N141I) displayed decreased anxiety
      behavior determined by the elevated plus maze test and the light dark box test.
      However, these mice showed biphasic ambulatory activity (hyperactivity followed
      by hypoactivity) in an open field test. Correlated well with the reduced anxiety,
      expression of GABA(A)alpha(1) receptor was higher whereas c-Fos was lower in the
      cortex, hippocampus, and amygdala of the mice expressing PS2 mutation than those
      of the wild-type PS2 or nontransgenic control mice. These data indicate that PS2
      mutation causes reduction of anxiety, and this effect may be related to the
      change of the expression of GABA(A)alpha(1) receptor and c-Fos. These findings
      could be useful in the understanding and the treatment of AD patients.

PMID- 18803282
TI  - Silencing of choline acetyltransferase expression by lentivirus-mediated RNA
      interference in cultured cells and in the adult rodent brain.
AB  - RNA interference (RNAi) is a potent mechanism for local silencing of gene
      expression and can be used to study loss-of-function phenotypes in mammalian
      cells. We used RNAi to knockdown specifically the expression of choline
      acetyltransferase (ChAT), the enzyme of acetylcholine biosynthesis, both in
      cultured cells and in the adult brain. We first identified a 19-nucleotide
      sequence in the coding region of rat and mouse ChAT transcripts that constitutes
      a target for potent silencing of ChAT expression by RNAi. We generated a
      lentiviral vector that produces both a small hairpin RNA (shRNA) targeting ChAT
      mRNAs and the enhanced green fluorescent protein (EGFP) reporter protein to
      facilitate identification of transduced cells. In the cholinergic cell line NG108
      15, there was at least 90% less of the ChAT protein, as measured by assaying its
      enzymatic activity, 3 days postinfection with this vector than in cells infected
      with a control vector. The vector was used to transduce cholinergic neurons in
      vivo and reduced ChAT expression strongly and specifically in the cholinergic
      neurons of the medial septum in adult rats, without affecting the expression of
      the vesicular acetylcholine transporter. This lentiviral vector is thus a
      powerful tool for specific inactivation of cholinergic neurotransmission and can
      therefore be used to study the role of cholinergic nuclei in the brain. This
      lentiviral-mediated RNAi approach will also allow the development of new animal
      models of diseases in which cholinergic neurotransmission is specifically
      altered.

PMID- 18803283
TI  - 9-Cis-retinoic acid reduces ischemic brain injury in rodents via bone
      morphogenetic protein.
AB  - Retinoic acid (RA), a biologically active derivative of vitamin A, has protective
      effects against damage caused by H(2)O(2) or oxygen-glucose deprivation in
      mesangial and PC12 cells. In cultured human osteosarcoma cells, RA enhances the
      expression of bone morphogenetic protein-7 (BMP7), a trophic factor that reduces
      ischemia- or neurotoxin-mediated neurodegeneration in vivo. The purpose of this
      study is to examine whether RA reduces ischemic brain injury through a BMP7
      mechanism. We found that intracerebroventricular administration of 9-cis-retinoic
      acid (9cRA) enhanced BMP7 mRNA expression, detected by RT-PCR, in rat cerebral
      cortex at 24 hr after injection. Rats were also subjected to transient focal
      ischemia induced by ligation of the middle cerebral artery (MCA) at 1 day after
      9cRA injection. Pretreatment with 9cRA increased locomotor activity and
      attenuated neurological deficits 2 days after MCA ligation. 9cRA also reduced
      cerebral infarction and TUNEL labeling. These protective responses were
      antagonized by the BMP antagonist noggin given 1 day after 9cRA injection. Taken
      together, our data suggest that 9cRA has protective effects against ischemia
      induced injury, and these effects involve BMPs.

PMID- 18803284
TI  - Vascular endothelial growth factor acutely reduces calcium influx via inhibition
      of the Ca2+ channels in rat hippocampal neurons.
AB  - Vascular endothelial growth factor (VEGF) protects neurons against ischemic
      injury. An overload of intracellular calcium ions (Ca(2+)) caused by the
      excessive release of glutamate is widely considered to be one of the molecular
      mechanisms of ischemic neuronal death. In the present study, we investigated
      whether VEGF could modulate the activity of Ca(2+) channels on the neuronal
      membrane. We used the Fluo-3 image method assisted by confocal laser scan
      microscopy to detect any Ca(2+) influx in primary cultured hippocampal neurons.
      Whole-cell patch-clamp techniques were used to record the activity of the high
      voltage-activated (HVA) Ca(2+) currents in the CA1 pyramidal neurons of
      hippocampal slices that were freshly prepared from neonatal brains of rats. The
      results obtained from the Fluo-3 image experiments showed that VEGF pretreatment
      of cultured neurons at a final concentration of 50, 100, or 200 ng/ml acutely and
      dose dependently attenuated the Ca(2+) influx induced by application of KCl (60
      mM) or glutamate (50 microM). This effect was blocked by SU1498, an antagonist of
      Flk-1 VEGF receptor. The influx of Ca(2+) returned to basal levels after removal
      of VEGF. Furthermore, electrophysiological recording data showed that VEGF could
      acutely reduce the amplitudes of the HVA Ca(2+) currents in a dose- and voltage
      dependent manner. The HVA Ca(2+) currents also returned to the levels of the
      control after removal of VEGF from the system. Taken together, the results
      obtained from the present study demonstrated that VEGF specifically reduced the
      influx of Ca(2+) via the inhibitory activity of the HVA Ca(2+) channels in
      hippocampal neurons.

PMID- 18803285
TI  - Generation of spinal motor neurons from human fetal brain-derived neural stem
      cells: role of basic fibroblast growth factor.
AB  - Neural stem cells (NSCs) have some specified properties but are generally
      uncommitted and so can change their fate after exposure to environmental cues. It
      is unclear to what extent this NSC plasticity can be modulated by extrinsic cues
      and what are the molecular mechanisms underlying neuronal fate determination.
      Basic fibroblast growth factor (bFGF) is a well-known mitogen for proliferating
      NSCs. However, its role in guiding stem cells for neuronal subtype specification
      is undefined. Here we report that in-vitro-expanded human fetal forebrain-derived
      NSCs can generate cholinergic neurons with spinal motor neuron properties when
      treated with bFGF within a specific time window. bFGF induces NSCs to express the
      motor neuron marker Hb9, which is blocked by specific FGF receptor inhibitors and
      bFGF neutralizing antibodies. This development of spinal motor neuron properties
      is independent of selective proliferation or survival and does not require high
      levels of MAPK activation. Thus our study indicates that bFGF can play an
      important role in modulating plasticity and neuronal fate of human NSCs and
      presumably has implications for exploring the full potential of brain NSCs for
      clinical applications, particularly in spinal motor neuron regeneration.

PMID- 18803286
TI  - Neurotrophin-3 stimulates neurogenetic proliferation via the extracellular signal
      regulated kinase pathway.
AB  - The effects of neurotrophin-3 (NT3) administered into the ventricular space of
      13.5-day-old mouse embryos on neurogenesis in the developing cerebral cortex were
      examined. 5-Bromo-2'-deoxyuridine (BrdU) was injected into pregnant mice 3 hr
      after the NT3 administration to label the neural progenitor cells. NT3 increased
      the number of BrdU-positive cells without altering their distribution. The
      increment in BrdU-positive cells 24 hr after the BrdU injection was attributed to
      Pax6-/BrdU-positive cells (neural stem cells), which was followed by a
      significant elevation of the number of Tuj1-/BrdU-positive cells (neurons) 36 or
      48 hr after the BrdU injection, suggesting that NT3 facilitated neurogenesis by
      acting in two sequential steps, i.e., causing proliferation of neural stem cells
      and generation of neurons from these progenitors. NT3 stimulated phosphorylation
      of extracellular signal-regulated kinase (ERK) 1/2 and ERK5 in the cortical
      progenitors, and the effects of NT3 on the increase in total BrdU-positive cells
      and Pax6-/BrdU-positive cells were diminished by an MEK inhibitor, suggesting the
      involvement of MEK-mediated ERK signal transduction in the NT3 actions.

PMID- 18803287
TI  - Chemoresistant tumor cell lines display altered epidermal growth factor receptor
      and HER3 signaling and enhanced sensitivity to gefitinib.
AB  - Deregulated signaling through the epidermal growth factor receptor (EGFR) is
      involved in chemoresistance. To identify the molecular determinants of
      sensitivity to the EGFR inhibitor gefitinib (Iressa, ZD1839) in chemoresistance,
      we compared the response of matched chemosensitive and chemoresistant glioma and
      ovarian cancer cell lines. We found that chemoresistant cell lines were 2- to 3
      fold more sensitive to gefitinib growth-inhibitory effects, because of decreased
      proliferation rather than survival. Sensitivity to gefitinib correlated with
      overexpression and constitutive phosphorylation of HER2 and HER3, but not EGFR,
      altered HER ligand expression, and enhanced activation of EGF-triggered EGFR
      pathway. No activating mutations were found in EGFR. Gefitinib fully inhibited
      EGF-induced and constitutive Akt activation only in chemoresistant cells. In
      parallel, gefitinib downregulated constitutively phosphorylated HER2 and HER3,
      and activated GSK3beta with a concomitant degradation of cyclin D1. Ectopically
      overexpressed HER2 on its own was insufficient to sensitize chemonaive cells to
      gefitinib. pHER3 coimmunoprecipitated with p85-PI3K in chemoresistant cells and
      gefitinib dissociated these complexes. siRNA-mediated inhibition of HER3
      decreased constitutive activation of Akt and sensitivity to gefitinib in
      chemoresistant cells. Our study indicates that in chemoresistant cells gefitinib
      inhibits both an enhanced EGF-triggered pathway and a constitutive HER3-mediated
      Akt activation, indicating that inhibition of HER3 together with that of EGFR
      could be relevant in chemorefractory tumors. Furthermore, in combination
      experiments gefitinib enhanced the effects of coadministered drugs more in
      chemoresistant than chemosensitive ovarian cancer cells. Combined treatment might
      be therapeutically beneficial in chemoresistant tumors from ovary and likely from
      other tissues.

PMID- 18803288
TI  - Clinical implication of recurrent copy number alterations in hepatocellular
      carcinoma and putative oncogenes in recurrent gains on 1q.
AB  - To elucidate the pathogenesis of hepatocellular carcinoma (HCC) and develop
      useful prognosis predictors, it is necessary to identify biologically relevant
      genomic alterations in HCC. In our study, we defined recurrently altered regions
      (RARs) common to many cases of HCCs, which may contain tumor-related genes, using
      whole-genome array-CGH and explored their associations with the clinicopathologic
      features. Gene set enrichment analysis was performed to investigate functional
      implication of RARs. On an average, 23.1% of the total probes were altered per
      case. Mean numbers of altered probes are significantly higher in high-grade,
      bigger and microvascular invasion (MVI) positive tumors. In total, 32 RARs (14
      gains and 18 losses) were defined and 4 most frequent RARs are gains in 1q21.1
      q32.1 (64.5%), 1q32.1-q44 (59.2%), 8q11.21-q24.3 (48.7%) and a loss in 17p13.3
      p12 (51.3%). Through focusing on RARs, we identified genes and functional
      pathways likely to be involved in hepatocarcinogenesis. Among genes in the
      recurrently gained regions on 1q, expression of KIF14 and TPM3 was significantly
      increased, suggesting their oncogenic potential in HCC. Some RARs showed the
      significant associations with the clinical features. Especially, the recurrent
      loss in 9p24.2-p21.1 and gain in 8q11.21-q24.3 are associated with the high tumor
      grade and MVI, respectively. Functional analysis showed that cytokine receptor
      binding and defense response to virus pathways are significantly enriched in high
      grade-related RARs. Taken together, our results and the strategy of analysis will
      help to elucidate pathogenesis of HCC and to develop biomarkers for predicting
      behaviors of HCC.

PMID- 18803289
TI  - Smoking and serum CA19-9 levels according to Lewis and secretor genotypes.
AB  - CA19-9, a marker for cancers of biliary tract, pancreas and colorectum, is not
      synthesized in those with no enzyme activity genotype (le/le) of Lewis (Le) gene.
      No enzyme activity genotype (se/se) of secretor (Se) gene is known to have an
      association with high serum CA19-9 levels. There are also variations in serum
      CA19-9 levels independent of the genotypes. This study aimed to examine the
      associations of serum CA19-9 levels with smoking, alcohol drinking and body mass
      index (BMI; kg/m(2)), after the adjustments of Le and Se genotypes. Subjects were
      486 health check-up examinees (158 males and 328 females) aged from 39 to 90
      years in Hokkaido, Japan. Genotyping was conducted for 3 polymorphisms; Le T59G
      (59T for Le allele and 59G for le allele), Se A385T (385A for Se allele and 385T
      for sej allele), and Se pseudogene (se5 allele). The genotypes of Le and Se were
      deterministic factors of serum CA19-9. Those with Le/Le & se/se had the highest
      mean, while CA19-9 was not detected or very low in those with le/le. Although no
      associations were observed with alcohol drinking and BMI, a significant
      association was observed with smoking. Among those with Le/Le, the geometric mean
      of CA19-9 was significantly lower for current smokers than for noncurrent smokers
      (p = 0.011 in 4-way ANOVA with age, sex and Se genotype). When hemoglobin A1c was
      further adjusted, the association became stronger (p = 0.0027). In addition to
      polymorphic variations, some components of cigarette smoke may influence the
      production or destruction of CA19-9.

PMID- 18803290
TI  - Relationship of SNCG, S100A4, S100A9 and LCN2 gene expression and DNA methylation
      in bladder cancer.
AB  - Microarray analysis of paired cultures of normal and cancerous urothelial cells
      revealed differences in cytokeratin and adhesion gene expression. Normal cells
      expressed autocrine growth factor genes more strongly whereas carcinoma cells
      were distinguished by concomitant expression of urothelial and epidermal
      differentiation markers. Expression of SNCG, S100A9 and LCN2 was also enhanced.
      In other cancers, overexpression of SNCG, LCN2 and S100A4 has been ascribed to
      DNA hypomethylation. We therefore investigated expression and methylation of
      SNCG, S100A4, S100A9 and LCN2 in urothelial cancer cell lines and tissues. SNCG
      and S100A4 were overexpressed in some cancer tissues and cell lines, but
      downregulated in others, whereas LCN2 and S100A9 were upregulated in few cancer
      cell lines, but regularly in tissues. Normal and cancerous urothelial cells
      expressing SNCG lacked promoter methylation. SNCG downregulation was associated
      with hypermethylation and could be reversed by the DNA methyltransferase
      inhibitor 5-aza-2'-deoxycytidine. S100A4 methylation at regulatory intronic sites
      and in the promoter region was lowest in leukocytes and fibroblasts, and denser
      in urothelial cells. Gene expression responded to 5-aza-2'-deoxycytidine. LCN2
      promoter methylation was variable and even less consistently related to
      expression. The S100A9 promoter was partially methylated in nonexpressing cells,
      but 5-aza-2'-deoxycytidine had no effect. Our data indicate that SNCG methylation
      is cell type-specific and the gene is hypermethylated in some urothelial cancers.
      S100A4, S100A9 and LCN2 are genes with moderate CpG-density that show a less
      stringent relationship between DNA methylation and gene expression. Therefore,
      changes in methylation of these genes in cancer should be interpreted cautiously.

PMID- 18803291
TI  - Social and mental health profiles of young male offenders in detention in Greece.
AB  - BACKGROUND: Among young offenders, mental health problems have been linked both
      to more serious delinquent acts and to high recidivism rates, but there has been
      little study of this in Greece. AIMS: The aims of this study were to describe
      demographic and family characteristics of young incarcerated male offenders, to
      determine the prevalence of mental disorders among them and to compare native
      Greeks with immigrants on these variables. METHODS: Ninety-three young males,
      randomly selected from the three main juvenile detention facilities in Greece,
      completed the Greek version of the Youth Self Report (YSR); the institutions'
      social workers completed a questionnaire designed for the study on the youths'
      demographics and offending. RESULTS: Results revealed over-representation of
      immigrants, high levels of psychosocial adversity (large family size, low
      parental educational level, poverty and family offending history) and high
      prevalence rates not only of externalizing disorders, such as conduct disorder,
      but also internalizing disorders, including anxiety, depression and somatizing
      problems. CONCLUSIONS AND PRACTICE IMPLICATIONS: Young males in Greek
      correctional institutions need support at many levels, and especially for mental
      health problems. This will have implications for staff training and juvenile
      justice system reform.

PMID- 18803292
TI  - Psychopathy and personality. An investigation of the relationship between the NEO
      Five Factor Inventory (NEO-FFI) and the Psychopathy Checklist-Revised (PCL-R) in
      a hospitalized sample of male offenders with personality disorder.
AB  - BACKGROUND: The concept of psychopathy, as measured by the Psychopathy Checklist
      Revised (PCL-R), has good reliability and validity and there is a small amount of
      literature relating it to more general personality traits. Such relationships
      have not, however, been demonstrated across a variety of populations. AIM: To
      examine the relationship between the PCL-R and the NEO-Five Factor Inventory (NEO
      FFI) in a sample of men detained in a secure hospital unit because of personality
      disorder and having been convicted of at least one criminal offence. METHOD: PCL
      R and NEO-FFI measures were obtained for 100 men as part of a pre-admission
      assessment to a specialist personality disorder treatment unit. RESULTS: After
      controlling for Intelligence Quotient (IQ) and scores on the other four NEO-FFI
      domains, PCL-R total scores were significantly negatively correlated with
      agreeableness (r = -0.36) and neuroticism (r = -0.22). No other correlations with
      total scores were significant. PCL-R Factor 1 scores were significantly
      negatively correlated with agreeableness (r = -0.31) and with neuroticism (r = 
      0.26) whereas Factor 2 scores were significantly positively correlated with
      extraversion (r = 0.22) and negatively with agreeableness (r = -0.21).
      CONCLUSIONS: Results were in line with findings from previous studies and were
      explained in part by considering how facets of the NEO-FFI map onto the concept
      of psychopathy. Further research is needed to ascertain whether similar
      relationships also apply among women, and to examine the relationship between
      psychopathy and specific facets of the five factor model.

PMID- 18803293
TI  - Evaluation of a treatment programme for alcohol-related aggression.
AB  - BACKGROUND: The development of effective treatments for alcohol-related
      aggression and violence is important in binge drinking cultures, as in parts of
      the UK.Aim The aim was to evaluate the progress and experience of 10 participants
      in Control of Violence for Angry Impulsive Drinkers (COVAID) using a single case
      methodology. METHOD: Participants completed 10 individual weekly sessions with
      trained facilitators following the COVAID manual. Change scores on psychometric
      questionnaires were examined by calculating clinical significance and reliability
      of change. Self-reports of alcohol consumption and aggression were examined.
      Follow-up data on convictions were collected. Participants were asked their
      opinions about COVAID. RESULTS: Scores on the Alcohol-Related Aggression
      Questionnaire (ARAQ) improved for nine participants; change was both clinically
      significant and reliable in five cases. Nine participants improved on the
      Controlled Drinking Self-Efficacy Scale (CDSES), with seven showing clinically
      significant improvement. Six participants reported a reduction in alcohol
      consumption from the first to the second half of the programme. At a mean of 29
      weeks post-treatment, none of the participants had been reconvicted for a violent
      offence. Participants reported finding COVAID useful and interesting. CONCLUSION:
      Overall, our findings support the possibility that COVAID may assist in reducing
      alcohol-related violence and violent offending.

PMID- 18803294
TI  - Psychometric properties of the Beck Depression Inventory-II with incarcerated
      male offenders aged 18-21 years.
AB  - BACKGROUND: The Beck Depression Inventory - Second Edition (BDI-II) is a self
      report measure of depression. Studies have shown it to have good psychometric
      properties with adult and adolescent clinical and non-clinical populations.
      However, this research has mostly been conducted with North American samples.
      AIMS/HYPOTHESES: To examine the psychometric characteristics of the BDI-II with
      male young adult offenders in the UK. METHODS: The BDI-II was administered to 117
      incarcerated male young adult offenders aged 18-21 years from the UK. RESULTS:
      The BDI-II showed good internal consistency and concurrent validity. Factor
      analysis revealed two factors, relating to cognitive-affective items and somatic
      items. The items loading on the two factors were very similar to those found in a
      North American adolescent (13-17 years) psychiatric inpatient sample. CONCLUSIONS
      AND IMPLICATIONS FOR FUTURE RESEARCH: The findings suggest that the BDI-II can be
      used with confidence in young adult male offenders. It would be useful to confirm
      its psychometric properties in other offender samples and establish offender
      population norms.

PMID- 18803295
TI  - Prevalence and correlates of traumatic brain injury among delinquent youths.
AB  - BACKGROUND: Delinquent youth frequently exhibit high-risk behaviours that can
      result in serious injury. However, little is known about traumatic brain injuries
      (TBIs) and their correlates in this population. AIMS: To examine the period
      prevalence and correlates of TBIs in delinquent youths. METHOD: Interviews were
      conducted with 720 (97.3%) residents of 27 Missouri Division of Youth Services
      rehabilitation facilities between March 1 and May 31, 2003. Participants [mean
      age (M age) = 15.5, standard deviation (SD) = 1.2, 87% male] completed measures
      assessing TBI, substance use, psychiatric symptoms, and antisocial
      traits/behaviours. TBI was defined as ever having sustained a head injury causing
      unconsciousness for more than 20 minutes. RESULTS: Nearly one-in-five youths
      (18.3%) reported a lifetime TBI. Youths with TBIs were significantly more likely
      than youths without to be male, have received a psychiatric diagnosis, report an
      earlier onset of criminal behaviour/substance use and more lifetime substance use
      problems and past-year criminal acts, evidence psychiatric symptoms, report
      lifetime suicidality, be impulsive, fearless, and external in locus of control
      and criminally victimized in the year preceding incarceration. Male gender and
      frequency of own criminal victimization were important predictors of TBI in
      multivariate analyses. Regression analyses adjusted for demographic factors,
      indicated that youths with TBIs were at significantly elevated risk for current
      depressive/anxious symptoms, antisocial behaviour, and substance abuse problems.
      CONCLUSIONS: TBI is common among delinquent youth and associated with wide
      ranging psychiatric dysfunction; however, the causal role of TBIs in the
      pathogenesis of co-morbid conditions remains unclear.

PMID- 18803296
TI  - COG1410, a novel apolipoprotein-E mimetic, improves functional and morphological
      recovery in a rat model of focal brain ischemia.
AB  - Apolipoprotein E (apoE) is the primary apolipoprotein synthesized in the brain in
      response to injury with known neuroprotective effects exerted through
      antioxidant, antiinflammatory, antiexcitotoxic, and neurotrophic mechanisms. We
      have previously demonstrated that COG1410, an apoE mimetic peptide, exerts
      neuroprotective and antiinflammatory effects in a murine model of traumatic brain
      injury (TBI). As in TBI, ischemia-reperfusion injury is a component of acute
      stroke, which displays a pharmacogenetic association with the APOE4 gene. Using
      an intraluminal middle cerebral occlusion (MCAO) model in rats, we found that a
      single intravenous injection of COG1410 at 120 min post-MCAO significantly
      improved vestibulomotor function, decreased poststroke locomotor asymmetry, and
      decreased infarct volume of the ipsilateral hemisphere. These results support
      further exploration of a novel apoE-mimetic peptide, COG1410, as a therapeutic
      treatment for stroke.

PMID- 18803297
TI  - Vitreous humor and albumin augment the proliferation of cultured retinal
      precursor cells.
AB  - Intravitreal injection is an important delivery route for studies involving the
      transplantation of various types of precursor cells to the retina; however, the
      effect on these cells of exposure to the vitreous microenvironment has not been
      specifically investigated. Here vitreous humor was evaluated for the potential to
      influence the proliferation of rat retinal precursor cells in vitro. Cells were
      isolated at embryonic day 19 and plated in standard proliferation medium in the
      presence or absence of fluid expressed from porcine vitreous humor. Cellular
      proliferation at different concentrations of vitreous fluid supplementation was
      quantified by using a (3)H-thymidine incorporation assay. Active components of
      vitreous fluid were partially characterized by gel filtration chromatography
      (GFC) and UV spectral analysis. The effect of each vitreous fraction on
      proliferation was determined as well. Results showed that addition of 20%
      vitreous fluid to primary rat retinal cultures significantly increased (3)H
      thymidine incorporation compared with growth medium without vitreous
      supplementation. A vitreous fraction showing growth-promoting activity was
      localized to a molecular mass range <1000 Da, consistent with ascorbic acid.
      Ascorbic acid was confirmed in vitreous fluid by UV spectral analysis. Growth
      augmenting activity was present in higher molecular mass vitreous fractions,
      consistent with protein components. Albumin, the major protein in vitreous fluid,
      was found to augment proliferation. Because vitreous-associated augmentation of
      retinal precursor proliferation remains an epidermal growth factor-dependent
      phenomenon, the proliferative status of transplanted cells in the vitreous cavity
      is likely determined by a combination of factors.

PMID- 18803298
TI  - Proteomic identification of nitrated brain proteins in traumatic brain-injured
      rats treated postinjury with gamma-glutamylcysteine ethyl ester: insights into
      the role of elevation of glutathione as a potential therapeutic strategy for
      traumatic brain injury.
AB  - Traumatic brain injury (TBI) occurs suddenly and has damaging effects to the
      brain that are dependent on the severity of insult. Symptoms can be mild,
      moderate, or severe. Oxidative damage is associated with traumatic brain injury
      through reactive oxygen/nitrogen species production. One such species,
      peroxynitrite, is elevated in TBI brain tissue (Orihara et al. [2001] Forensic
      Sci. Int. 123:142-149; Deng et al. [2007] Exp. Neurol. 205:154-165).
      Peroxynitrite can react with carbon dioxide and decompose to produce NO(2) and
      carbonate radicals, which in turn can lead to 3-nitrotyrosine, an index of
      protein nitration. Gamma-glutamylcysteine ethyl ester (GCEE) is an ethyl ester
      moiety of gamma-glutamylcysteine, an agent that up-regulates glutathione (GSH)
      production in brain (Drake et al. [2002] J. Neurosci. Res. 68:776-784). Many
      preclinical studies of TBI have employed pretreatment of animals with proposed
      beneficial agents prior to the injury itself. However, in the real world of TBI,
      treatment begins postinjury. Hence, insights into agents that improve outcome
      following injury are desperately needed. This study is one of the first to
      investigate a potential GSH-based therapy for TBI postinjury. Protein carbonyls,
      an index of protein oxidation, were significantly elevated in brain of animals
      subjected to TBI. However, if, after TBI, GCEE was administered i.p., protein
      carbonyl levels were significantly reduced. Similarly, 3-nitrotyrosine levels
      were elevated in brain following TBI but significantly decreased following TBI if
      GCEE was administered i.p. Redox proteomics analysis showed that several brain
      proteins were nitrated after TBI. However, if GCEE was given i.p. following TBI,
      many of these proteins were protected from nitration. The results are encouraging
      and are discussed with reference to potential therapeutic strategies for TBI
      involving elevated GSH.

PMID- 18803299
TI  - Nicotinic receptor stimulation protects nigral dopaminergic neurons in rotenone
      induced Parkinson's disease models.
AB  - Parkinson's disease (PD) is the second most common neurodegenerative disease and
      is characterized by dopaminergic (DA) neuronal cell loss in the substantia nigra.
      Although the entire pathogenesis of PD is still unclear, both environmental and
      genetic factors contribute to neurodegeneration. Epidemiologic studies show that
      prevalence of PD is lower in smokers than in nonsmokers. Nicotine, a releaser of
      dopamine from DA neurons, is one of the candidates of antiparkinson agents in
      tobacco. To assess the protective effect of nicotine against rotenone-induced DA
      neuronal cell toxicity, we examined the neuroprotective effects of nicotine in
      rotenone-induced PD models in vivo and in vitro. We observed that simultaneous
      subcutaneous administration of nicotine inhibited both motor deficits and DA
      neuronal cell loss in the substantia nigra of rotenone-treated mice. Next, we
      analyzed the molecular mechanisms of DA neuroprotective effect of nicotine
      against rotenone-induced toxicity with primary DA neuronal culture. We found that
      DA neuroprotective effects of nicotine were inhibited by dihydro-beta
      erythroidine (DHbetaE), alpha-bungarotoxin (alphaBuTx), and/or PI3K-Akt/PKB
      (protein serine/threonine kinase B) inhibitors, demonstrating that rotenone
      toxicity on DA neurons are inhibited via activation of alpha4beta2 or alpha7
      nAChRs-PI3K-Akt/PKB pathway or pathways. These results suggest that the rotenone
      mouse model may be useful for assessing candidate antiparkinson agents, and that
      nAChR (nicotinic acetylcholine receptor) stimulation can protect DA neurons
      against degeneration.

PMID- 18803300
TI  - Increase in mitochondrial density within axons and supporting cells in response
      to demyelination in the Plp1 mouse model.
AB  - We used the Plp1-overexpressing transgenic mouse model to investigate whether
      progressive demyelination of axons results in adaptive changes involving
      mitochondria within the axons. These models have myelinated axons from birth but
      gradually lose myelin and develop axonal loss associated with progressive
      neurological disability analogous to patients with secondary progressive
      mulltiple sclerosis (SPMS). At 1 and 2 months, electron microscopy demonstrated a
      significant increase in intraaxonal mitochondrial density in the homozygous line
      72 Plp1-overexpressing mice compared with wild type (1.43 +/- 0.31 vs. 0.84 +/-
      0.16 microm(-3), P = 0.031; 1.66 +/- 0.11 vs. 0.92 +/- 0.43 microm(-3), P = 0.02)
      and a significant increase at 1 and 4 months in the density of mitochondria in
      the surrounding cells in the same mice (1.86 +/- 0.31 vs. 0.81 +/- 0.30 microm(
      3), P = 0.006; 2.77 +/- 0.44 vs. 1.37 +/- 0.42 microm(-3), P = 0.016). At both 1
      and 4 months, COX histochemistry and time-lapse histochemistry demonstrated a
      significant increase in mitochondrial activity and rate of mitochondrial activity
      in the homozygous Plp1-overexpressing mouse optic nerve compared with the wild
      type (112.37 +/- 11.9 vs. 136.89 +/- 9.1 MeanD, P = 0.006; 128.02 +/- 3.0 vs.
      188.77 +/- 9.7 MeanD P < 0.001; Rate -0.78 +/- 0.25 vs. -0.58 +/- 0.15 MeanD min(
      1), P < 0.001; -1.48 +/- 0.15 vs. 0.51 +/- 0.17 MeanD min(-1), P < 0.001,
      respectively). We propose that adaptive changes involving mitochondria occur
      within CNS axons in Plp1-overexpressing mice, which may be detrimental to long
      term viability. Analogous changes occurring in chronically demyelinated axons in
      MS lesions would be one mechanism increasing axonal vulnerability in SPMS.

PMID- 18803302
TI  - The glycoprotein fibulin-3 regulates morphology and motility of olfactory
      ensheathing cells in vitro.
AB  - The primary olfactory pathway in adult mammals has retained a remarkable
      potential for self-repair. A specialized glial cell within the olfactory nerve,
      called olfactory ensheathing cell (OEC), and their associated extracellular
      matrix are thought to play an important role during regenerative events in this
      system. To gain insight into novel molecules that could mediate the OEC-supported
      growth of axons within the olfactory nerve, gene expression profiling experiments
      were conducted which revealed high expression of the glycoprotein fibulin-3 in
      OECs. This observation was confirmed with quantitative PCR. In vivo, the
      distribution of all members of the fibulin family, fibulin-3 included, was
      localized to the lamina propria underneath the olfactory epithelium, in close
      association within olfactory nerve bundles. To manipulate fibulin-3 gene
      expression in cultured OECs, lentiviral vector constructs were designed to either
      transgenically express or knock-down fibulin-3. Experimental data showed that
      increased levels of fibulin-3 induced profound morphological changes in cultured
      OECs, impeded with their migratory abilities and also suppressed OEC-mediated
      neurite outgrowth. Knock-down of fibulin-3 levels resulted in reduced OEC
      proliferation. In conclusion, the data provide novel insights into a putative
      role for fibulin-3 in the regulation of cell migration and neurite outgrowth
      within the primary olfactory pathway.

PMID- 18803301
TI  - Low-density lipoprotein receptors regulate microglial inflammation through c-Jun
      N-terminal kinase.
AB  - Apolipoprotein E (apoE) has been implicated in modulating the central nervous
      system (CNS) inflammatory response. However, the molecular mechanisms involved in
      apoE-dependent immunomodulation are poorly understood. We hypothesize that apoE
      alters the CNS inflammatory response by signaling via low-density lipoprotein
      (LDL) receptors in glia. To address this hypothesis, we used a small bioactive
      peptide formed from the receptor-binding domain of apoE, apoE peptide (EP), to
      study LDL receptor signaling in microglia. To model glial activation, we treated
      primary mouse microglia and the microglial cell line BV2 with lipopolysaccharide
      (LPS) and studied two inflammatory responses: an increase in nitric oxide
      production (NO) and a decrease in apoE production. We found that treatment of
      primary microglia and BV2 cells with EP attenuated LPS-induced NO accumulation
      and apoE reduction in a dose-dependent manner. Using the receptor-associated
      protein to block ligand binding to members of the LDL receptor family, we found
      that EP attenuated both of these LPS-induced inflammatory responses via LDL
      receptors. We studied two intracellular signaling cascades associated with apoE:
      c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK).
      LPS induced both ERK and JNK activation, whereas EP induced ERK activation, but
      drastically reduced JNK activation. Inhibition of JNK with SP600125 reduced LPS
      induced NO production and apoE reduction in a dose-dependent manner. Treatment of
      microglia with suboptimal EP in combination with JNK inhibitor enhanced
      attenuation of LPS-induced NO production. These data suggest that microglial LDL
      receptors regulate JNK activation, which is necessary for apoE modulation of the
      inflammatory response.

PMID- 18803303
TI  - NOD2 plays an important role in the inflammatory responses of microglia and
      astrocytes to bacterial CNS pathogens.
AB  - While glial cells are recognized for their roles in maintaining neuronal
      function, there is growing appreciation that resident central nervous system
      (CNS) cells initiate and/or augment inflammation following trauma or infection.
      We have recently demonstrated that microglia and astrocytes constitutively
      express nucleotide-binding oligomerization domain-2 (NOD2), a member of the novel
      nucleotide-binding domain leucine-rich repeat region containing a family of
      proteins (NLR) that functions as an intracellular receptor for a minimal motif
      present in all bacterial peptidoglycans. In this study, we have confirmed the
      functional nature of NOD2 expression in astrocytes and microglia and begun to
      determine the relative contribution that this NLR makes in inflammatory CNS
      responses to clinically relevant bacterial pathogens. We demonstrate the
      increased association of NOD2 with its downstream effector molecule, Rip2 kinase,
      in primary cultures of murine microglia and astrocytes following exposure to
      bacterial antigens. We show that this cytosolic receptor underlies the ability of
      muramyl dipeptide to augment the production of inflammatory cytokines by glia
      following exposure to specific ligands for disparate Toll-like receptor
      homologues. In addition, we demonstrate that NOD2 is an important component in
      the in vitro inflammatory responses of resident glia to N. meningitidis and B.
      burgdorferi antigens. Finally, we have established that NOD2 is required, at
      least in part, for the astrogliosis, demyelination, behavioral changes, and
      elevated inflammatory cytokine levels observed following in vivo infection with
      these pathogens. As such, we have identified NOD2 as an important component in
      the generation of damaging CNS inflammation following bacterial infection.

PMID- 18803305
TI  - Expression of syndecan-2 in the amoeboid microglial cells and its involvement in
      inflammation in the hypoxic developing brain.
AB  - The present study examined the expression of heparan sulphate proteoglycan,
      syndecan-2 (Sdc-2) in the corpus callosum and the amoeboid microglial cells (AMC)
      in the neonatal rat brain in response to hypoxia. In 1-day old Wistar rats
      subjected to hypoxia the mRNA and protein expression of Sdc-2 in the corpus
      callosum, heavily populated by AMC, was increased up to 3 days after the hypoxic
      exposure. Immunoexpression of Sdc-2 was localized in AMC as confirmed by double
      labeling using microglial marker. Primary cultures of microglial cells subjected
      to hypoxia showed a significant increase in Sdc-2 expression. Application of Sdc
      2 to microglial cultures under hypoxia increased the release of tumor necrosis
      factor-alpha, interleukin-1beta, chemokine (C-C motif) ligand 2 (CCL2), and
      chemokine (C-X-C motif) ligand 12 (CXCL12) by the microglial cells. Additionally,
      Sdc-2 enhanced the production of reactive oxygen species (ROS) by microglia
      subjected to hypoxia. Edaravone [3-methyl-1phenyl-2-pyrazolin-5-one], an
      antioxidant drug, suppressed the hypoxia- and Sdc-2-induced increased production
      of cytokines, chemokines, and ROS. In the light of these findings, we suggest
      that Sdc-2 plays an important role in microglial production of inflammatory
      cytokines, chemokines, and ROS in hypoxic conditions. In this connection,
      edaravone suppressed the hypoxia- and Sdc-2-induced increased cytokine and ROS
      production suggesting its therapeutic potential in ameliorating
      neuroinflammation.

PMID- 18803304
TI  - Proteomic analysis of the retina: removal of RPE alters outer segment assembly
      and retinal protein expression.
AB  - The mechanisms that regulate the complex physiological task of photoreceptor
      outer segment assembly remain an enigma. One limiting factor in revealing the
      mechanism(s) by which this process is modulated is that not all of the role
      players who participate in this process are known. The purpose of this study was
      to determine some of the retinal proteins that likely play a critical role in
      regulating photoreceptor outer segment assembly. To do so, we analyzed and
      compared the proteome map of tadpole Xenopus laevis retinal pigment epithelium
      (RPE)-supported retinas containing organized outer segments with that of RPE
      deprived retinas containing disorganized outer segments. Solubilized proteins
      were labeled with CyDye fluors followed by multiplexed two-dimensional
      separation. The intensity of protein spots and comparison of proteome maps was
      performed using DeCyder software. Identification of differentially regulated
      proteins was determined using nanoLC-ESI-MS/MS analysis. We found a total of 27
      protein spots, 21 of which were unique proteins, which were differentially
      expressed in retinas with disorganized outer segments. We predict that in the
      absence of the RPE, oxidative stress initiates an unfolded protein response.
      Subsequently, downregulation of several candidate Muller glial cell proteins may
      explain the inability of photoreceptors to properly fold their outer segment
      membranes. In this study, we have used identification and bioinformatics
      assessment of proteins that are differentially expressed in retinas with
      disorganized outer segments as a first step in determining probable key molecules
      involved in regulating photoreceptor outer segment assembly.

PMID- 18803306
TI  - Endogenous signals initiating inflammation in the injured nervous system.
AB  - Glial cells are known to respond to a variety of neural injuries and play an
      important role in tissue damage and repair in the injured nervous system. This
      glial response, which is initially characterized by the expression of
      proinflammatory cytokines and chemokines and the attraction of microglial cells
      toward sites of injury, literally occurs within seconds to minutes of the injury.
      This suggests that signals that are endogenous to the nervous system are
      responsible for initiating neuroinflammation. In this review, we summarize the
      most recent advances made in the identification of these endogenous signals and
      describe the receptors and signaling pathways by which these ligands stimulate
      the production of cytokines and chemokines. Among these endogenous damage signals
      are ligands for toll-like receptors, including several heat shock proteins and
      extracellular matrix components, as well as self-derived RNA and DNA and
      associated proteins. Growing evidence also suggests that nucleotides released
      upon injury and acting through P2 receptors, such as ATP and UTP or their
      analogues, could serve as endogenous signals for the rapid response of glial
      cells.

PMID- 18803307
TI  - Differential erbB signaling in astrocytes from the cerebral cortex and the
      hypothalamus of the human brain.
AB  - Studies in rodents have shown that astroglial erbB tyrosine kinase receptors are
      key regulatory elements in neuron-glia communication. Although both astrocytes
      and deregulation of erbB functions have been implicated in the pathogenesis of
      many common human brain disorders, erbB signaling in native human brain
      astrocytes has never been explored. Taking advantage of our ability to perform
      primary cultures from the cortex and the hypothalamus of human fetuses, we
      conducted a thorough analysis of erbB signaling in human astrocytes. We showed
      that human cortical astrocytes express erbB1, erbB2, and erbB3, whereas human
      hypothalamic astrocytes express erbB1, erbB2, and erbB4 receptors. Ligand
      dependent activation of different erbB receptor heterodimeric complexes in these
      two populations of astrocytes translated into different morphological and
      proliferative responses. Although morphological plasticity was more pronounced in
      hypothalamic astrocytes than in cortical astrocytes, the former showed a lower
      mitogenic potential. Decreasing erbB4 expression via siRNA-mediated gene
      knockdown revealed that erbB4 constitutively restrains basal proliferative
      activity in hypothalamic astrocytes. We further show that treatment of human
      astrocytes with a protein kinase C activator results in rapid tyrosine
      phosphorylation of erbB receptors that involves cleavage of endogenous membrane
      bound erbB ligands by metalloproteinases. Together, these results indicate that
      erbB signaling in primary human brain astrocytes is functional, region-specific,
      and can be activated in a paracrine and/or autocrine manner. In addition, by
      revealing that some aspects of astroglial erbB signaling are different between
      human and rodents, our results provide a molecular framework to explore the
      potential involvement of astroglial erbB signaling deregulation in human brain
      disorders.

PMID- 18803308
TI  - Pituicyte modulation of neurohormone output.
AB  - Pituicytes have long been suspected to play a role in the regulation of
      neurohypophysial hormone output. This role has been mainly ascribed to
      morphological changes in these cells and subsequent modifications of their tight
      structural relationships with surrounding nerve terminals and capillaries. These
      entirely reversible changes are brought about by physiological states such as
      parturition, lactation, or dehydration, and it was inferred that they should
      facilitate neurohormone output, based on concerted analyses of in vitro, in situ,
      and ex vivo experiments. Pituicyte stellation, the in vitro counterpart of these
      morphological changes, can be induced by beta-adrenergic or A1-adenosine receptor
      activation, and appears to result from inhibition of the small GTPase RhoA. Actin
      depolymerization is the key event allowing stellation. Vasopressin and oxytocin
      reverse stellation and return pituicytes to their basal shape by activating
      Cdc42, another small GTPase that reorganizes the actin cytoskeleton in a cortical
      position. Adenosine and neurohormones also have opposite actions on the efflux of
      taurine, a local messenger that is released by pituicytes in hypotonic conditions
      and accordingly inhibits vasopressin output from axon terminals. As adenosine is
      likely generated from endogenous ATP co-released with neurohormones and broken
      down by local ectoATPases, these data suggest a subtle balance between a positive
      and a negative feedback on vasopressin output operated, respectively, by
      adenosine and vasopressin to maintain hydromineral homeostasis. A theoretical
      scenario is presented to account for the putative sequence of pituicyte-related
      events following disturbance of the hydromineral system.

PMID- 18803309
TI  - Survival and disability in a cohort of neural tube defect births in Dublin,
      Ireland.
AB  - BACKGROUND: Neural tube defects (NTDs) are a major cause of death and disability.
      Periconceptional folic acid prevents up to 70% of these malformations but public
      health campaigns to increase use of supplements have had disappointing results:
      The proposed mandatory fortification of bread products in Ireland has raised
      concerns about possible side effects. We examined data collected on a cohort of
      children born with NTDs in an era before fortification/supplementation to
      illustrate the serious consequences in terms of survival and disability. METHODS:
      All 623 infants born with NTDs in the Dublin area between 1976 and 1987 were
      included. Information was collected on mortality and length of survival for those
      who died, and for those who survived at least 5 years, interview-based data were
      collected on age, place of residence, prevalence of hydrocephalus, degree of
      disability, schooling, and IQ. RESULTS: Seventy-four births (12%) were stillborn.
      Of the livebirths only 41% were alive at 5 years. Factors associated with
      mortality were type of lesion, level of lesion, presence of other defects,
      hydrocephalus, year of birth, and gestation. Of the children who survived to 5
      years or more, 75% had a disability and 56% were severely disabled. Type of
      lesion and level of lesion influenced disability risk. Of the survivors, 51% of
      children had mobility limitations, 59% were incontinent, 42% had hydrocephalus,
      and 17% had intellectual disability. CONCLUSIONS: These findings illustrate the
      devastating consequences of NTDs and underline the importance of effective
      intervention programs with folic acid for prevention.

PMID- 18803310
TI  - Transvaginal sonographic diagnosis of female urethral diverticula.
AB  - PURPOSE: We report our experience with transvaginal sonography (TVUS) in the
      diagnosis of female urethral diverticulum (UD). METHOD: We reviewed the TVUS
      examinations of 4 patients with a clinical diagnosis of UD and correlated the
      sonographic findings with the operative findings, especially regarding the UD's
      size, content, and location. RESULTS: All UDs were demonstrated on TVUS. The
      size, content, and location of the UD correlated well with the operative
      findings. CONCLUSION: TVUS is accurate in diagnosis and determination of the
      size, content, and location of female UD.

PMID- 18803311
TI  - Sonographic study of the development of fetal corpus callosum in a Chinese
      population.
AB  - PURPOSE: The observation of fetal corpus callosum (CC) is important for the
      prenatal sonographic assessment of fetal central nervous system development. The
      aim of this study was to investigate the development of normal Chinese fetal CC.
      METHOD: CC measurements were performed using high-resolution transabdominal
      sonography on 622 Chinese fetuses between 16 and 39 weeks' gestation. The
      correlation between CC size and gestational age was investigated. RESULTS: The
      fetal CC length increased in a linear fashion during pregnancy. The length of the
      CC as a function of gestational age was expressed by the following regression
      equation: length (mm) = -9.567 + 1.495 x gestational age (weeks) (r = 0.932, p <
      0.001). CONCLUSION: Knowledge of normal CC appearance may help identify
      developmental anomalies and enable accurate prenatal counseling.

PMID- 18803312
TI  - Sonographic assessment of the lateral femoral cutaneous nerve.
AB  - PURPOSE: To evaluate the ability of high-frequency sonography to evaluate the
      lateral femoral cutaneous nerve (LFCN). METHODS: A cadaveric study was performed
      on 5 cadavers to outline the normal course of the LFCN. Next, 37 LFCNs in 21
      volunteers were evaluated via sonography with a 5-13-MHz linear-array transducer.
      RESULTS: The LFCN was easily identified in our dissections. It always entered the
      thigh under the inguinal ligament and coursed superficially to the sartorius
      muscle. In 2/10 (20%) cases, anatomical variants were observed. Sonography
      revealed the LFCN in 26/37 (70%) cases. The relationships of the nerve with the
      deep circumflex iliac artery, the anterior superior iliac spine, and the
      sartorius were visualized. Neuromas were observed bilaterally in 1 volunteer.
      CONCLUSION: The LFCN can be seen in the groin with the aid of sonography.

PMID- 18803313
TI  - Segmental cystic renal disease: sonographic and CT findings.
AB  - Segmental cystic renal disease is a unique benign condition that requires no
      treatment. It can be confused on imaging, especially on sonography, with other
      more common cystic renal diseases and sometimes cystic malignancy. We report a
      case of segmental cystic renal disease with typical imaging features on
      sonography and CT for which nephrectomy was avoided.

PMID- 18803314
TI  - Evaluation of the accuracy and reliability of two 3-dimensional sonography
      methods in volume measurement of small structures: an in vitro phantom study.
AB  - PURPOSE: To evaluate the accuracy and reliability of two 3-dimensional (3D)
      ultrasound imaging and measurement techniques in volume measurements using custom
      made phantoms. METHODS: A total of 20 phantoms with irregular-shaped test objects
      of known volume (2-9.7 ml) were constructed. The phantoms were scanned using an
      automated mechanical 3D sonography technique and a free-hand 3D sonography
      technique. The volumes of the test objects were measured with "parallel planes"
      and "rotating planes" techniques, respectively. The measured volumes were
      compared with the actual volumes of the test objects. To evaluate inter- and
      intraoperator measurement variability, the phantoms were scanned twice by 2
      different operators. RESULTS: Both the automated mechanical and the free-hand 3D
      sonography techniques were accurate and reliable. Automated mechanical 3D
      sonography with the parallel planes technique (accuracy, 81.5-83.4%;
      reproducibility, 91.1%; repeatability, 98.8-99.1%) was slightly more accurate and
      reliable than the free-hand rotating planes technique (accuracy, 74.7-84.2%;
      reproducibility, 88.4%; repeatability, 97.3-98%), but the differences were not
      statistically significant. CONCLUSION: Both the automated and freehand volume
      measurement techniques evaluated in this study are accurate and reliable.

PMID- 18803315
TI  - Biology and pathology of nonmyelinating Schwann cells.
AB  - The CNS contains relatively few unmyelinated nerve fibers, and thus benefits from
      the advantages that are conferred by myelination, including faster conduction
      velocities, lower energy consumption for impulse transmission, and greater
      stability of point-to-point connectivity. In the PNS many fibers or regions of
      fibers the Schwann do not form myelin. Examples include C fibers nociceptors,
      postganglionic sympathetic fibers, and the Schwann cells associated with motor
      nerve terminals at neuromuscular junctions. These examples retain a degree of
      plasticity and a capacity to sprout collaterally that is unusual in myelinated
      fibers. Nonmyelin-forming Schwann cells, including those associated with
      uninjured fibers, have the capacity to act as the "first responders" to injury or
      disease in their neighborhoods.

PMID- 18803316
TI  - Introduction. Schwann cell biology.

PMID- 18803317
TI  - Development of the Schwann cell lineage: from the neural crest to the myelinated
      nerve.
AB  - The myelinating and nonmyelinating Schwann cells in peripheral nerves are derived
      from the neural crest, which is a transient and multipotent embryonic structure
      that also generates the other main glial subtypes of the peripheral nervous
      system (PNS). Schwann cell development occurs through a series of transitional
      embryonic and postnatal phases, which are tightly regulated by a number of
      signals. During the early embryonic phases, neural crest cells are specified to
      give rise to Schwann cell precursors, which represent the first transitional
      stage in the Schwann cell lineage, and these then generate the immature Schwann
      cells. At birth, the immature Schwann cells differentiate into either the
      myelinating or nonmyelinating Schwann cells that populate the mature nerve
      trunks. In this review, we will discuss the biology of the transitional stages in
      embryonic and early postnatal Schwann cell development, including the phenotypic
      differences between them and the recently identified signaling pathways, which
      control their differentiation and maintenance. In addition, the role and
      importance of the microenvironment in which glial differentiation takes place
      will be discussed.

PMID- 18803318
TI  - Neuregulin-1, a key axonal signal that drives Schwann cell growth and
      differentiation.
AB  - Interactions between neuronal and glial cells are crucial for establishing a
      functional nervous system. Many aspects of Schwann cell development and
      physiology are regulated by neuronal signals; possibly the most spectacular is
      the elaboration of the myelin sheath. An extensive line of research has revealed
      that one neuronal factor, termed "neuregulin", promotes Schwann cell growth and
      survival, migration along the extending axon, and myelination. The versatility of
      glial responses elicited by this factor is thus clearly astounding.

PMID- 18803319
TI  - Regulation of Schwann cell function by the extracellular matrix.
AB  - Laminins and collagens are extracellular matrix proteins that play essential
      roles in peripheral nervous system development. Laminin signals regulate Schwann
      cell proliferation and survival as well as actin cytoskeleton dynamics, which are
      essential steps for radial sorting and myelination of peripheral axons by Schwann
      cells. Collagen and their receptors promote Schwann cell adhesion, spreading, and
      myelination as well as neurite outgrowth. In this article, we will review the
      recent advances in the studies of laminin and collagen function in Schwann cell
      development.

PMID- 18803321
TI  - Molecular domains of myelinated axons in the peripheral nervous system.
AB  - Myelinated axons are organized into a series of specialized domains with distinct
      molecular compositions and functions. These domains, which include the node of
      Ranvier, the flanking paranodal junctions, the juxtaparanodes, and the internode,
      form as the result of interactions with myelinating Schwann cells. This domain
      organization is essential for action potential propagation by saltatory
      conduction and for the overall function and integrity of the axon.

PMID- 18803320
TI  - The function of RhoGTPases in axon ensheathment and myelination.
AB  - RhoGTPases are molecular switches that integrate extracellular signals to perform
      diverse cellular responses. This ability relies on the network of proteins
      regulating RhoGTPases activity and localization, and on the interaction of
      RhoGTPases with many different cellular effectors. Myelination is an ideal place
      for RhoGTPases regulation, as it is the result of fine orchestration of many
      stimuli from at least two cell types. Recent work has revealed that RhoGTPases
      are required for Schwann cells to sort, ensheath, and myelinate axons. Here, we
      will review these recent advances showing the critical roles for RhoGTPases in
      various aspects of Schwann development and myelination, including the recent
      discovery of their involvement in Charcot-Marie-Tooth disease. Comparison with
      potential roles of RhoGTPases in central nervous system myelination will be
      drawn.

PMID- 18803323
TI  - Negative regulation of myelination: relevance for development, injury, and
      demyelinating disease.
AB  - Dedifferentiation of myelinating Schwann cells is a key feature of nerve injury
      and demyelinating neuropathies. We review recent evidence that this
      dedifferentiation depends on activation of specific intracellular signaling
      molecules that drive the dedifferentiation program. In particular, we discuss the
      idea that Schwann cells contain negative transcriptional regulators of
      myelination that functionally complement positive regulators such as Krox-20, and
      that myelination is therefore determined by a balance between two opposing
      transcriptional programs. Negative transcriptional regulators should be expressed
      prior to myelination, downregulated as myelination starts but reactivated as
      Schwann cells dedifferentiate following injury. The clearest evidence for a
      factor that works in this way relates to c-Jun, while other factors may include
      Notch, Sox-2, Pax-3, Id2, Krox-24, and Egr-3. The role of cell-cell signals such
      as neuregulin-1 and cytoplasmic signaling pathways such as the extracellular
      related kinase (ERK)1/2 pathway in promoting dedifferentiation of myelinating
      cells is also discussed. We also review evidence that neurotrophin 3 (NT3),
      purinergic signaling, and nitric oxide synthase are involved in suppressing
      myelination. The realization that myelination is subject to negative as well as
      positive controls contributes significantly to the understanding of Schwann cell
      plasticity. Negative regulators are likely to have a major role during injury,
      because they promote the transformation of damaged nerves to an environment that
      fosters neuronal survival and axonal regrowth. In neuropathies, however,
      activation of these pathways is likely to be harmful because they may be key
      contributors to demyelination, a situation which would open new routes for
      clinical intervention.

PMID- 18803324
TI  - Interactions between Schwann cells and macrophages in injury and inherited
      demyelinating disease.
AB  - In this article we first discuss the factors that regulate macrophage
      recruitment, activation, and myelin phagocytosis during Wallerian degeneration
      and some of the factors involved in the termination of inflammation at the end of
      the period of Wallerian degeneration after peripheral nerve injuries. In
      particular, we deal with the early events that trigger chemokine and cytokine
      expression; the role of phospholipase A(2) in initiating the breakdown of compact
      myelin, and chemokine, cytokine expression; and the role of MCP-1, MIP-1alpha,
      and IL-1beta in macrophage recruitment and myelin phagocytosis. We also discuss
      how inflammation may be switched off and the recently identified role of the Nogo
      receptor on activated macrophages in the clearance of these cells from the
      injured nerve. In the second half of the article we focus on the role of certain
      Schwann cell borne cytokines and chemokines, such as M-CSF and MCP-1 as well as
      intracellular signaling that regulate their expression in animal models of
      inherited demyelinating disease. Additionally, we present the preservation of
      sensory nerves fibers from macrophage attack in these animal models as a
      challenging paradigm for the development of putative treatment approaches.
      Finally, we also discuss the similarities and differences in these Schwann cell
      macrophage responses in injury-induced Wallerian degeneration and inherited
      demyelinating diseases. Knowledge of the molecular mechanisms underlying Schwann
      cell-macrophage interaction under pathological conditions is an important
      prerequisite to develop effective treatment strategies for various peripheral
      nerve disorders.

PMID- 18803322
TI  - The molecular machinery of myelin gene transcription in Schwann cells.
AB  - During late fetal life, Schwann cells in the peripheral nerves singled out by the
      larger axons will transit through a promyelinating stage before exiting the cell
      cycle and initiating myelin formation. A network of extra- and intracellular
      signaling pathways, regulating a transcriptional program of cell differentiation,
      governs this progression of cellular changes, culminating in a highly
      differentiated cell. In this review, we focus on the roles of a number of
      transcription factors not only in myelination, during normal development, but
      also in demyelination, following nerve trauma. These factors include
      specification factors involved in early development of Schwann cells from neural
      crest (Sox10) as well as factors specifically required for transitions into the
      promyelinating and myelinating stages (Oct6/Scip and Krox20/Egr2). From this
      description, we can glean the first, still very incomplete, contours of a gene
      regulatory network that governs myelination and demyelination during development
      and regeneration.

PMID- 18803325
TI  - Molecular mechanisms of inherited demyelinating neuropathies.
AB  - The past 15 years have witnessed the identification of more than 25 genes
      responsible for inherited neuropathies in humans, many associated with primary
      alterations of the myelin sheath. A remarkable body of work in patients, as well
      as animal and cellular models, has defined the clinical and molecular genetics of
      these illnesses and shed light on how mutations in associated genes produce the
      heterogeneity of dysmyelinating and demyelinating phenotypes. Here, we review
      selected recent developments from work on the molecular mechanisms of these
      disorders and their implications for treatment strategies.

PMID- 18803327
TI  - Identification of candidate tumor suppressor genes inactivated by promoter
      methylation in melanoma.
AB  - Tumor suppressor genes (TSGs) are sometimes inactivated by transcriptional
      silencing through promoter hypermethylation. To identify novel methylated TSGs in
      melanoma, we carried out global mRNA expression profiling on a panel of 12
      melanoma cell lines treated with a combination of 5-Aza-2-deoxycytidine (5AzadC)
      and an inhibitor of histone deacetylase, Trichostatin A. Reactivation of gene
      expression after drug treatment was assessed using Illumina whole-genome
      microarrays. After qRT-PCR confirmation, we followed up 8 genes (AKAP12,
      ARHGEF16, ARHGAP27, ENC1, PPP1R3C, PPP1R14C, RARRES1, and TP53INP1) by
      quantitative DNA methylation analysis using mass spectrometry of base-specific
      cleaved amplification products in panels of melanoma cell lines and fresh tumors.
      PPP1R3C, ENC1, RARRES1, and TP53INP1, showed reduced mRNA expression in 35-59% of
      the melanoma cell lines compared to melanocytes and which was correlated with a
      high proportion of promoter methylation (>40-60%). The same genes also showed
      extensive promoter methylation in 6-25% of the tumor samples, thus confirming
      them as novel candidate TSGs in melanoma.

PMID- 18803326
TI  - How does the Schwann cell lineage form tumors in NF1?
AB  - Neurofibromas are benign tumors of peripheral nerve that occur sporadically or in
      patients with the autosomal dominant tumor predisposition syndrome
      neurofibromatosis type 1 (NF1). Multiple neurofibroma subtypes exist which differ
      in their site of occurrence, their association with NF1, and their tendency to
      undergo transformation to become malignant peripheral nerve sheath tumors
      (MPNSTs), the most common malignancy associated with NF1. Most NF1 patients carry
      a constitutional mutation of the NF1 tumor suppressor gene. Neurofibromas develop
      in these patients when an unknown cell type in the Schwann cell lineage loses its
      remaining functional NF1 gene and initiates a complex series of interactions with
      other cell types; these interactions may be influenced by aberrant expression of
      growth factors and growth factor receptors and the action of modifier genes.
      Cells within certain neurofibroma subtypes subsequently accumulate additional
      mutations affecting the p19(ARF)-MDM2-TP53 and p16INK4A-Rb signaling cascades,
      mutations of other as yet unidentified genes, and amplification of growth factor
      receptor genes, resulting in their transformation into MPNSTs. These observations
      have been validated using a variety of transgenic and knockout mouse models that
      recapitulate neurofibroma and MPNST pathogenesis. A new generation of mouse
      models is also providing important new insights into the identity of the cell
      type in the Schwann cell lineage that gives rise to neurofibromas. Our improving
      understanding of the mechanisms underlying the pathogenesis of neurofibromas and
      MPNSTs raises intriguing new questions about the origin and pathogenesis of these
      neoplasms and establishes models for the development of new therapies targeting
      these neoplasms.

PMID- 18803328
TI  - Integration of genomic and gene expression data of childhood ALL without known
      aberrations identifies subgroups with specific genetic hallmarks.
AB  - Pediatric acute lymphoblastic leukemia (ALL) comprises genetically distinct
      subtypes. However, 25% of cases still lack defined genetic hallmarks. To identify
      genomic aberrancies in childhood ALL patients nonclassifiable by conventional
      methods, we performed a single nucleotide polymorphisms (SNP) array-based genomic
      analysis of leukemic cells from 29 cases. The vast majority of cases analyzed
      (19/24, 79%) showed genomic abnormalities; at least one of them affected either
      genes involved in cell cycle regulation or in B-cell development. The most
      relevant abnormalities were CDKN2A/9p21 deletions (7/24, 29%), ETV6 (TEL)/12p13
      deletions (3/24, 12%), and intrachromosomal amplifications of chromosome 21
      (iAMP21) (3/24, 12%). To identify variation in expression of genes directly or
      indirectly affected by recurrent genomic alterations, we integrated genomic and
      gene expression data generated by microarray analyses of the same samples. SMAD1
      emerged as a down-regulated gene in CDKN2A homozygous deleted cases compared with
      nondeleted. The JAG1 gene, encoding the Jagged 1 ligand of the Notch receptor,
      was among a list of differentially expressed (up-regulated) genes in ETV6-deleted
      cases. Our findings demonstrate that integration of genomic analysis and gene
      expression profiling can identify genetic lesions undetected by routine methods
      and potential novel pathways involved in B-progenitor ALL pathogenesis.

PMID- 18803329
TI  - Species-specific insecticide resistance to imidacloprid and fipronil in the rice
      planthoppers Nilaparvata lugens and Sogatella furcifera in East and South-east
      Asia.
AB  - BACKGROUND: In 2003 the development of insecticide resistance against
      neonicotinoids in the brown planthopper (BPH), Nilaparvata lugens (Stal)
      (Homoptera: Delphacidae), was first observed in Thailand and has since been found
      in other Asian countries such as Vietnam, China and Japan. However, the LD(50)
      values of BPH and the whitebacked planthopper (WBPH), Sogatella furcifera
      (Horvath), against both neonicotinoid and phenylpyrazole insecticides have been
      poorly reported in many Asian countries. RESULTS: The topical LD(50) values for
      imidacloprid in the BPH populations collected from East Asia (Japan, China,
      Taiwan) and Vietnam in 2006 were 4.3-24.2 microg g(-1) and were significantly
      higher than those collected from the Philippines (0.18-0.35 microg g(-1)). The
      BPH populations indicated a positive cross-resistance between imidacloprid and
      thiamethoxam. Almost all the WBPH populations from Japan, Taiwan, China, Vietnam
      and the Philippines had extremely large LD(50) values (19.7-239 microg g(-1) or
      more) for fipronil, except for several populations from the Philippines and
      China. CONCLUSION: Species-specific changes in insecticide susceptibility were
      found in Asian rice planthoppers (i.e. BPH for imidacloprid and WBPH for
      fipronil). Insecticide resistance in BPH against imidacloprid occurred in East
      Asia and Indochina, but not in the Philippines. In contrast, insecticide
      resistance in WBPH against fipronil occurred widely in East and South-east Asia.

PMID- 18803330
TI  - Strontium isotope ratios (87Sr/86Sr) of tooth enamel: a comparison of solution
      and laser ablation multicollector inductively coupled plasma mass spectrometry
      methods.
AB  - Strontium isotope ratios (87Sr/86Sr) in tooth enamel provide a means to
      investigate migration and landscape use in humans and other animals. Established
      methods for measuring (87)Sr/(86)Sr in teeth use bulk sampling (5-20 mg) and
      labor-intensive elemental purification procedures before analysis by either
      thermal ionization mass spectrometry (TIMS) or multicollector inductively coupled
      plasma mass spectrometry (MC-ICP-MS). Another method for measuring 87Sr/86Sr is
      laser ablation MC-ICP-MS, but concerns have been expressed about its accuracy for
      measuring tooth enamel. In this study we test the precision and accuracy of the
      technique by analyzing 30 modern rodent teeth from the Sterkfontein Valley, South
      Africa by laser ablation MC-ICP-MS and solution MC-ICP-MS. The results show a
      mean difference in 87Sr/86Sr measured by laser ablation and by solution of 0.0003
      +/- 0.0002. This degree of precision is well within the margin necessary for
      investigating the potential geographic origins of humans or animals in many areas
      of the world. Because laser ablation is faster, less expensive, and less
      destructive than bulk sampling solution methods, it opens the possibility for
      conducting 87Sr/86Sr analyses of intra-tooth samples and small and/or rare
      specimens such as micromammal and fossil teeth.

PMID- 18803331
TI  - Reduction of in-source collision-induced dissociation and thermolysis of
      sulopenem prodrugs for quantitative liquid chromatography/electrospray ionization
      mass spectrometric analysis by promoting sodium adduct formation.
AB  - Six chromatographically resolved sulopenem prodrugs were monitored for their
      potential to undergo both in-source collision-induced dissociation (CID) and
      thermolysis. Initial Q1 scans for each prodrug revealed the formation of intense
      [Prodrug2 + H]+, [Prodrug2 + Na]+, [Prodrug + Na]+, and [Sulopenem + Na]+ ions.
      Non-adduct-associated sulopenem ([Sulopenem + H]+) along with several additional
      lower mass ions were also observed. Product ion scans of [Prodrug3 + Na]+ showed
      the retention of the sodium adduct in the collision cell continuing down to
      opening of the beta-lactam ring. In-source CID and temperature experiments were
      conducted under chromatographic conditions while monitoring several of the latter
      ion transitions (i.e., adducts, dimers and degradants/fragments) for a given
      prodrug. The resulting ion profiles indicated the regions of greatest stability
      for temperature and declustering potential (DP) that provided the highest signal
      intensity for each prodrug and minimized in-source degradation. The heightened
      stability of adduct ions, relative to their appropriate counterpart (i.e., dimer
      to dimer adduct and prodrug to prodrug adduct ions), was observed under elevated
      temperature and DP conditions. The addition of 100 microM sodium to the mobile
      phase further enhanced the formation of these more stable adduct ions, yielding
      an optimal [Prodrug + Na]+ ion signal at temperatures from 400 to 600 degrees C.
      A clinical liquid chromatography/tandem mass spectrometry (LC/MS/MS) assay for
      sulopenem prodrug PF-04064900 in buffered whole blood was successfully validated
      using sodium-fortified mobile phase and the [PF-04064900 + Na]+ ion for
      quantitation. A conservative five-fold increase in sensitivity from previously
      validated preclinical assays using the [PF-04064900 + H]+ precursor ion was
      achieved.

PMID- 18803332
TI  - The fallaxidin peptides from the skin secretion of the Eastern Dwarf Tree Frog
      Litoria fallax. Sequence determination by positive and negative ion electrospray
      mass spectrometry: antimicrobial activity and cDNA cloning of the fallaxidins.
AB  - The glandular skin secretion of the Eastern Dwarf Tree Frog Litoria fallax
      contains nine peptides named fallaxidins. The sequences of these peptides were
      elucidated using a combination of positive and negative electrospray mass
      spectrometry together with Edman sequencing. Among these peptides are: (i)
      fallaxidins 1.1 and 2.1 which have the sequences YFPIPI-NH2 and FWPFM-NH2. The
      activities of these peptides are unknown, but it has been shown that they are not
      smooth muscle active, opioids or antimicrobially active, nor do they effect
      proliferation of lymphocytes; (ii) two weakly active antibiotics, fallaxidins 3.1
      and 3.2 (e.g. fallaxidin 3.1, GLLDLAKHVIGIASKL-NH2), and a moderately active
      antibiotic fallaxidin 4.1 (GLLSFLPKVIGVIGHLIHPPS-OH). Fallaxidin 4.1 has an
      unusual sequence for an antibiotic, containing three Pro residues together with a
      C-terminal CO2H group. cDNA cloning has confirmed the identity of the nine
      isolated peptides from L. fallax, together with five additional peptides not
      detected in the peptide profile. The pre-regions of the nine preprofallaxidins
      are conserved and similar to those of the caerin peptides from L. caerulea and L.
      splendida, suggesting that the fallaxidin and caerin peptides, although
      significantly different in sequence, originated from a common ancestor gene.

PMID- 18803333
TI  - Quantification of small molecules in plasma with direct analysis in real time
      tandem mass spectrometry, without sample preparation and liquid chromatographic
      separation.
AB  - Recently, a new ion source, Direct Analysis in Real Time (DART), has been
      introduced which allows direct biological sample introduction into a mass
      spectrometry (MS) system. The elimination of conventionally required sample
      preparation and separation by high-performance liquid chromatography (HPLC) prior
      to MS analysis represents a remarkable opportunity to reduce assay turn-around
      time, environmental impact and capital/manpower investment. This new technology
      initially was used in various qualitative applications to directly detect
      chemicals on solid surfaces, in liquids and gases. In this study, a DART source
      operating under ambient pressure with ground potential was installed onto a Sciex
      4000 tandem mass spectrometer and employed in the sample analysis of plasma based
      on direct introduction into the DART-MS/MS system. Reasonable precision and
      accuracy (%CV and %Error, both <10%) were achieved of a significant number of
      compounds tested in biological fluids. In addition, the limit of detection for
      80% of the tested compounds reached 5 ng/mL or lower which is sufficient for
      pharmaceutical drug discovery support. Finally, experimental conditions that
      significantly impacted assay performance were investigated with respect to
      optimization and limitation. Because of its simplicity, fast data acquisition (3
      5 s) and low cost, DART has the potential to significantly impact quantitative
      pharmaceutical analysis in biological matrices.

PMID- 18803334
TI  - Accelerated proteolysis in alternating electric fields for peptide mapping.
AB  - Sinusoidal alternating voltages (typically 5 V) were employed to enhance the
      efficiency of proteolysis for peptide mapping in this work. Protein solutions
      containing trypsin were allowed to digest with the assistance of alternating
      electric fields (AEFs) between a pair of platinum wire electrodes in Eppendorf
      tubes. The feasibility and performance of the novel proteolysis approach were
      investigated by the digestion of several standard proteins. It was demonstrated
      that AEFs significantly accelerated in-solution proteolysis and the digestion
      time was substantially reduced to 5 min. The digests were identified by matrix
      assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF
      MS) with sequence coverages that were comparable to those obtained by using
      conventional 12-h in-solution proteolysis. The suitability of AEF-assisted
      proteolysis to real protein samples was demonstrated by digesting and identifying
      human serum albumin in gel separated from human serum by sodium dodecyl
      sulphate/polyacrylamide gel electrophoresis (SDS-PAGE). The present proteolysis
      strategy is simple and efficient and will find a wide range of applications in
      protein identification.

PMID- 18803335
TI  - GlycoMiner: a new software tool to elucidate glycopeptide composition.
AB  - New computer software, GlycoMiner, has been developed to automatically identify
      tandem (MS/MS) spectra obtained in liquid chromatography/mass spectrometry
      (LC/MS) runs which correspond to N-glycopeptides. The program complements
      conventional proteomics analysis, and can be used in a high-throughput
      environment. The program interprets the spectra and determines the structure of
      the corresponding glycopeptides. GlycoMiner runs under Windows, can process
      spectra obtained on various instruments, and can be downloaded from our website
      (w3.chemres.hu/ms/glycominer). The algorithm works similarly to a human expert;
      evaluates the low mass oxonium ions; deduces oligosaccharide losses from the
      protonated molecule; and identifies the mass of the peptide residue. The program
      has been tested on tryptic digests of two glycopeptides: AGP (which has five
      different N-glycosylation sites) and transferrin (with two N-glycosylation
      sites). Results have been evaluated both manually and by GlycoMiner. Out of 3132
      MS/MS spectra 338 were found to correspond to glycopeptides; identification by
      GlycoMiner showed a 0.1% false positive and 0.1% false negative rate. From these
      it was possible to identify 196 glycan structures manually; GlycoMiner correctly
      identified all of these, with no false positives. The rest were low quality
      spectra, not suitable for structure assignment.

PMID- 18803336
TI  - Detecting signals of opioid analgesic abuse: application of a spatial mixed
      effect poisson regression model using data from a network of poison control
      centers.
AB  - PURPOSE: The recent rise in the non-medical use of opioid analgesics in the US
      has underscored the importance of comprehensive post-marketing surveillance of
      these products. To assist pharmacovigilance efforts, we developed a methodology
      for detecting geo-specific "signals" of potential outbreaks of prescription drug
      abuse by 3-digit ZIP (3DZ) code. METHODS: The number of intentional exposure
      calls involving nine specific opioid analgesics were obtained from eight regional
      poison control centers between first quarter 2003 and fourth quarter 2004. The
      unit of analysis was a combination of drug-quarter/year-3DZ. We fitted an
      empirical Bayes mixed effects Poisson-Gamma regression model that adjusted for
      differences across 3DZs in opioid analgesic exposure. A relative report rate (RR)
      >or=3 at a probability of >0.95 was the signal threshold criterion. RESULTS: A
      total of 15,769 valid drug-time-3DZ combinations were identified. Of these, 1.9%
      (n = 294) met the signal threshold criterion. The number of signals generated per
      drug-quarter/year-3DZ combination ranged from 0 to 13. The largest number of
      signals were those involving methadone (n = 71), hydrocodone (n = 57), and
      branded oxycodone extended-release (n = 45). Signals for methadone and branded
      oxycodone extended-release were predominantly clustered in Appalachia.
      Hydrocodone-related signals showed less geographic clustering with approximately
      26% reported from California, and the remainder from other regions in the US.
      CONCLUSIONS: Our results show marked regional differences in reported abuse of
      specific opioid analgesics. Additional research is needed to determine the
      sensitivity and specificity of signals obtained using this spatial mixed effect
      Poisson regression model.

PMID- 18803337
TI  - An integrated system for planning, navigation and robotic assistance for skull
      base surgery.
AB  - BACKGROUND: We developed an image-guided robot system to provide mechanical
      assistance for skull base drilling, which is performed to gain access for some
      neurosurgical interventions, such as tumour resection. The motivation for
      introducing this robot was to improve safety by preventing the surgeon from
      accidentally damaging critical neurovascular structures during the drilling
      procedure. METHODS: We integrated a Stealthstation navigation system, a NeuroMate
      robotic arm with a six-degree-of-freedom force sensor, and the 3D Slicer
      visualization software to allow the robotic arm to be used in a navigated,
      cooperatively-controlled fashion by the surgeon. We employed virtual fixtures to
      constrain the motion of the robot-held cutting tool, so that it remained in the
      safe zone that was defined on a preoperative CT scan. RESULTS: We performed
      experiments on both foam skull and cadaver heads. The results for foam blocks cut
      using different registrations yielded an average placement error of 0.6 mm and an
      average dimensional error of 0.6 mm. We drilled the posterior porus acusticus in
      three cadaver heads and concluded that the robot-assisted procedure is clinically
      feasible and provides some ergonomic benefits, such as stabilizing the drill. We
      obtained postoperative CT scans of the cadaver heads to assess the accuracy and
      found that some bone outside the virtual fixture boundary was cut. The typical
      overcut was 1-2 mm, with a maximum overcut of about 3 mm. CONCLUSIONS: The image
      guided cooperatively-controlled robot system can improve the safety and
      ergonomics of skull base drilling by stabilizing the drill and enforcing virtual
      fixtures to protect critical neurovascular structures. The next step is to
      improve the accuracy so that the overcut can be reduced to a more clinically
      acceptable value of about 1 mm.

PMID- 18803338
TI  - Real-time motion tracking in image-guided oral implantology.
AB  - BACKGROUND: As a crucial part of an image-guided oral implantology system
      (IGOIS), intra-operative motion tracking is important in terms of accuracy and
      efficiency. The tracking method, including the relevant algorithms, is described
      in detail. METHODS: The conventional CAD method is proposed to build the three
      dimensional (3D) surgical instrument models. With the application of the optical
      tracking device, calibration can be carried out. Three tracking algorithms are
      presented, and 'tracking based on registration of RCS to VCS' is regarded as the
      most efficient of these. In order to evaluate the tracking accuracy, the landmark
      coordinates are respectively obtained through pre-operative CT data and intra
      operative tracking, so that the deviation can be calculated. RESULTS: The result
      data reveal that FRE and TRE of IGOIS are, respectively, 0.27 +/- 0.11 mm and
      0.77 +/- 0.04 mm through a phantom experiment. CONCLUSIONS: The experiment
      demonstrates the accuracy and reliability of IGOIS. The tracking method can be
      extended to other surgical navigation systems in various areas.

PMID- 18803339
TI  - Hand-held robotic instrument for dextrous laparoscopic interventions.
AB  - BACKGROUND: Surgical instruments used in many types of minimally invasive
      procedures are rigid or only limitedly flexible. Some common tasks like suturing,
      require precise and dextrous movements that are difficult to perform by means of
      instruments with limited degrees of freedom (DOF). METHODS: A hand-held
      lightweight and ergonomic robotic instrument with a 3-DOF roll-pitch-roll end
      effector has been developed, which can be controlled by the surgeon with one hand
      like a conventional instrument. RESULTS: The instrument is composed by a handle
      part and an end-effector. The handle part has been developed taking into account
      a control mode study for laparoscopic instruments and it allows direct mapping
      between the orientation of handle and that of the end-effector. CONCLUSION: The
      instrument presented is the result of a global study involving mechanical,
      electronic and ergonomic aspects, with the aim of developing an instrument that
      enhances the dexterity of the surgeon while having an intuitive interface.

PMID- 18803340
TI  - Overview of the vascular interventional robot.
AB  - BACKGROUND: Conventional vascular interventional surgery (VIS) is manually
      performed under fluoroscopic guidance, requiring lead protection for the
      surgeons. In order to reduce the X-ray irradiation, the robot has been introduced
      to VIS in this study. The purpose of this article is to provide a comprehensive
      summary of the vascular interventional robot (VIR). METHODS: A retrospective
      review of the currently published literature on VIR is discussed. The overview
      details the key technologies of VIR. RESULTS: Surgeons operate the robot far away
      from the patient, so protecting themselves from X-ray irradiation. The robot
      system carries out the VIS precisely and provides three-dimensional visualization
      of vasculature that can be used for preoperative planning and intra-operative
      navigation. CONCLUSIONS: The use of the vascular interventional robot appears
      safe and feasible for vascular interventional surgery. VIR can offer radiation
      safety to surgeon and enhance surgical accuracy.

PMID- 18803341
TI  - Pre-clinical remote telesurgery trial of a da Vinci telesurgery prototype.
AB  - BACKGROUND: The objective of this study was to perform a pre-clinical remote
      telesurgery trial of a da Vinci telesurgery prototype on a surgical-grade virtual
      private network. METHODS: A da Vinci telesurgery-enabled prototype was used to
      conduct surgical trials across a 17 MB/s bandwidth VPNe network spanning 2848 km
      round-trip landline distance from London, Ontario, to Halifax, Nova Scotia,
      Canada. The outcomes measured during the trial were surgical times and quality of
      anastomoses. RESULTS: Network configuration resulted in observed latencies of 370
      ms with 140 ms due to transport delay. The da Vinci telesurgery prototype
      performed well subjectively and average porcine pyeloplasty anastomotic times
      were 20.7 +/- 4.7 min. CONCLUSIONS: This work constitutes an early evaluation of
      the da Vinci telesurgery prototype for conceptually remote telesurgical
      operations. This study clearly demonstrated the feasibility of remote telesurgery
      using the da Vinci platform to perform a complex surgical task.

PMID- 18803342
TI  - Weight loss and isotopic shifts for water drops frozen on a liquid nitrogen
      surface.
AB  - A liquid nitrogen freezing method was used to collect raindrops for the
      determination of isotope-size distribution. Water drops that fall onto a surface
      of liquid nitrogen stay suspended for 10 to 20 s, until their temperature reaches
      the Leidenfrost point (126 K). As their temperature falls to the freezing point,
      they release their heat by thermal conduction. At the freezing point, latent heat
      of fusion is released, along with a significant loss of water. After freezing
      completely, the ice droplets stay suspended, cooling by thermal conduction until
      they reach the Leidenfrost point. They then lose buoyancy and start sinking.
      Consistent isotopic changes of 1.5 +/- 0.4 and 0.33 +/- 0.05 per thousand for
      hydrogen and oxygen, respectively, were found for droplets with radii between 1.0
      and 1.5 mm. Isotope fractionation appeared to occur at the same time as water
      loss, as the droplets were freezing, in what was probably a kinetic effect.

PMID- 18803343
TI  - Determination of the fatty acyl profiles of phosphatidylethanolamines by tandem
      mass spectrometry of sodium adducts.
AB  - Phosphatidylethanolamines (PEs) are one of the major constituents of cellular
      membranes, and, along with other phospholipid classes, have an essential role in
      the physiology of cells. Profiling of phospholipids in biological samples is
      currently done using mass spectrometry (MS). In this work we describe the MS
      fragmentation of sodium adducts of 2-oleoyl-1-palmitoyl-sn-glycero-3
      phosphatidylethanolamine (POPE) and 2-linoleoyl-1-palmitoyl-sn-glycero-3
      phosphatidylethanolamine (PLPE). This study was performed by electrospray
      ionization tandem mass spectrometry (ESI-MS/MS) using three different instruments
      and also by matrix-assisted laser desorption/ionization tandem mass spectrometry
      (MALDI-MS/MS). All MS/MS spectra show product ions related to the polar head
      fragmentation and product ions related to the loss of acyl chains. In ESI-MS/MS
      spectra, the product ions [M+Na-R1COOH-43]+ and [M+Na-R2COOH-43]+ show different
      relative abundance, as well as [M+Na-R1COOH]+ and [M+Na-R2COOH]+ product ions,
      allowing identification of both fatty acyl residues of PEs, and their specific
      location. MALDI-MS/MS shows the same product ions reported before and other ions
      generated by charge-remote fragmentation of the C3-C4 bond (gamma-cleavage) of
      fatty acyl residues combined with loss of 163 Da. These fragment ions, [M+Na-(R2
      C2H3)-163]+ and [M+Na-(R1-C2H3)-163]+, show different relative abundances, and
      the product ion formed by the gamma-cleavage of sn-2 is the most abundant.
      Overall, differences noted that are important for identification and location of
      fatty acyl residues in the glycerol backbone are: relative abundance between the
      product ions [M+Na-R1COOH-43]+ > [M+Na-R2COOH-43]+ in ESI-MS/MS spectra; and
      relative abundance between the product ions [M+Na-(R2-C2H3)-163]+ > [M+Na-(R1
      C2H3)-163]+ in MALDI-MS/MS spectra.

PMID- 18803344
TI  - Enrichment of low molecular weight serum proteins using acetonitrile
      precipitation for mass spectrometry based proteomic analysis.
AB  - A rapid acetonitrile (ACN)-based extraction method has been developed that
      reproducibly depletes high abundance and high molecular weight proteins from
      serum prior to mass spectrometric analysis. A nanoflow liquid
      chromatography/tandem mass spectrometry (nano-LC/MS/MS) multiple reaction
      monitoring (MRM) method for 57 high to medium abundance serum proteins was used
      to characterise the ACN-depleted fraction after tryptic digestion. Of the 57
      targeted proteins 29 were detected and albumin, the most abundant protein in
      serum and plasma, was identified as the 20th most abundant protein in the
      extract. The combination of ACN depletion and one-dimensional nano-LC/MS/MS
      enabled the detection of the low abundance serum protein, insulin-like growth
      factor-I (IGF-I), which has a serum concentration in the region of 100 ng/mL. One
      dimensional sodium dodecyl sulfate/polyacrylamide gel electrophoresis (SDS-PAGE)
      analysis of the depleted serum showed no bands corresponding to proteins of
      molecular mass over 75 kDa after extraction, demonstrating the efficiency of the
      method for the depletion of high molecular weight proteins. Total protein
      analysis of the ACN extracts showed that approximately 99.6% of all protein is
      removed from the serum. The ACN-depletion strategy offers a viable alternative to
      the immunochemistry-based protein-depletion techniques commonly used for removing
      high abundance proteins from serum prior to MS-based proteomic analyses.

PMID- 18803345
TI  - NMR spectroscopic elucidation of the structure and stereochemistry of tricyclic 3
      styrylpyrazolines.
AB  - Diastereomeric mixtures of tricyclic 3-styrylpyrazolines have been prepared by
      the reaction of 3-cynnamylidenechroman-4-ones and their 1-thio analogs with
      hydrazine in hot acetic acid or propionic acid solutions. The diastereomeric
      mixtures were separated by column chromatography to obtain the pure
      diastereomers. The elucidation of their structure and stereochemistry and
      complete (1)H and (13)C assignments have been performed by a combination of
      various one- and two-dimensional NMR experiments.

PMID- 18803346
TI  - Synthesis and NMR elucidation of novel penta-cycloundecane amine derivatives as
      potential antituberculosis agents.
AB  - The synthesis and NMR elucidation of five novel penta-cycloundecane amine
      derivatives are reported. These compounds are potential antituberculosis agents.
      The (1)H and (13)C spectra showed major overlapping of methine signals of the
      cage skeleton making it extremely difficult to elucidate these compounds. The
      overlapping occurs as a result of the additions made to the carbonyl carbon (C
      8/C-11) of the cage. The two-dimensional NMR technique proved to be a useful tool
      in overcoming this problem. All compounds reported are meso compounds thereby not
      only simplifying the NMR structure elucidation, but also making it indeed
      possible.

PMID- 18803347
TI  - Acute mesenteric ischemia after cardio-pulmonary bypass surgery.
AB  - Acute mesenteric ischemia (AMI) is a highly-lethal surgical emergency. Several
      pathophysiologic events (arterial obstruction, venous thrombosis and diffuse
      vasospasm) lead to a sudden decrease in mesenteric blood flow.
      Ischemia/reperfusion syndrome of the intestine is responsible for systemic
      abnormalities, leading to multi-organ failure and death. Early diagnosis is
      difficult because the clinical presentation is subtle, and the biological and
      radiological diagnostic tools lack sensitivity and specificity. Therapeutic
      options vary from conservative resuscitation, medical treatment, endovascular
      techniques and surgical resection and revascularization. A high index of
      suspicion is required for diagnosis, and prompt treatment is the only hope of
      reducing the mortality rate. Studies are in progress to provide more accurate
      diagnostic tools for early diagnosis. AMI can complicate the post-operative
      course of patients following cardio-pulmonary bypass (CPB). Several factors
      contribute to the systemic hypo-perfusion state, which is the most frequent
      pathophysiologic event. In this particular setting, the clinical presentation of
      AMI can be misleading, while the laboratory and radiological diagnostic tests
      often produce inconclusive results. The management strategies are controversial,
      but early treatment is critical for saving lives. Based on the experience of our
      team, we consider prompt exploratory laparotomy, irrespective of the results of
      the diagnostic tests, is the only way to provide objective assessment and
      adequate treatment, leading to dramatic reduction in the mortality rate.

PMID- 18803348
TI  - Satiety testing: ready for the clinic?
AB  - Drink tests are advocated as an inexpensive, noninvasive technique to assess
      gastric function in patients with a variety of upper digestive symptoms. Many
      patients with dyspeptic complaints will achieve satiation or develop symptoms at
      ingested volumes below those typically required to achieve these endpoints in
      controls. Substantial variation in test performance exists and a greater degree
      of standardization is required. Additionally, it remains unclear exactly what
      drink tests measure, as correlations with measures of gastric sensation,
      accommodation and emptying are modest at best. Finally, results of drink tests do
      not guide therapy. At present, these tests are best reserved for research studies
      and are not advocated for use in clinical practice.

PMID- 18803349
TI  - Neuroendocrine tumors of the gastro-entero-pancreatic system.
AB  - Gastro-entero-pancreatic (GEP) neuroendocrine tumors (NETs) are rare neoplasms,
      although their prevalence has increased substantially over the past three
      decades. Moreover, there has been an increased clinical recognition and
      characterization of these neoplasms. They show extremely variable biological
      behavior and clinical course. Most NETs have endocrine function and secrete
      peptides and neuroamines that cause distinct clinical syndromes, including
      carcinoid syndrome; however, many are clinically silent until late presentation
      with mass effects. Investigation and management should be individualized for each
      patient, taking into account the likely natural history of the tumor and general
      health of the patient. Management strategies include surgery for cure or
      palliation, and a variety of other cytoreductive techniques, and medical
      treatment including chemotherapy, and biotherapy to control symptoms due to
      hormone release and tumor growth, with somatostatin analogues (SSAs) and alpha
      interferon. New biological agents and somatostatin-tagged radionuclides are under
      investigation. Advances in the therapy and development of centers of excellence
      which coordinate multicenter studies, are needed to improve diagnosis, treatment
      and therefore survival of patients with GEP NETs.

PMID- 18803351
TI  - Anti-tumor activity of erlotinib in the BxPC-3 pancreatic cancer cell line.
AB  - AIM: To investigate the effect and mechanism of action of erlotinib, an epidermal
      growth factor receptor (EGFR) small molecule tyrosine kinase inhibitor (TKI), in
      the human pancreatic cancer cell line BxPC-3 both in vitro and in vivo. METHODS:
      In vitro, human pancreatic cancer cell line BxPC-3 was exposed to varying
      concentrations of erlotinib, and its effects on proliferation, cell cycle
      distribution, apoptosis and the expression of pro- and antiapoptotic factors such
      as bcl-2, bcl-xl, bax and bak, and the expression of vascular endothelial cell
      growth factor (VEGF) were measured with 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) assay, flow cytometric analysis, terminal
      deoxynucleotidyl transferase-mediated nick end labeling assay (TUNEL), and
      reverse transcription-polymerase chain reaction (RT-PCR). Potential effect of
      erlotinib on angiogenesis was examined by tube formation assay. Tumor growth
      suppression was observed in xenografted nude mice with pancreatic cancer in vivo.
      Immunohistochemical (IHC) staining for EGFR and factor VIII-related antigen was
      undertaken to detect the microvessel density and VEGF expression in tumor tissue
      in xenograft nude mice. RESULTS: Erlotinib, as a single agent, repressed BxPC-3
      cell growth in a dose-dependent manner, triggered G(1) arrest and induced cell
      apoptosis, and suppressed capillary formation of endothelium in vitro.
      Expressions of VEGF were significantly down-regulated at a high concentration of
      200 mumol/L, however, the expressions of bcl-2 and bcl-xl were decreased at 50
      mumol/L. In vivo, Erlotinib-treated mice demonstrated a reduced tumor volume,
      weight and microvessel density as compared to the control. IHC staining showed
      decreased expression of EGFR and RT-PCR had lower VEGF expression in treated
      mice. CONCLUSION: The in vitro and in vivo findings provide evidence that BxPC-3
      cells are inhibited with erlotinib treatment. Inhibition of EGFR may be a
      promising adjuvant chemotherapy strategy in pancreatic cancer treatment.

PMID- 18803350
TI  - "Rescue" regimens after Helicobacter pylori treatment failure.
AB  - Helicobacter pylori (H pylori) infection is the main cause of gastritis,
      gastroduodenal ulcer disease, and gastric cancer. After more than 20 years of
      experience in H pylori treatment, in my opinion, the ideal regimen to treat this
      infection is still to be found. Currently, apart from having to know first-line
      eradication regimens well, we must also be prepared to face treatment failures.
      Therefore, in designing a treatment strategy we should not focus on the results
      of primary therapy alone, but also on the final (overall) eradication rate. The
      choice of a "rescue" treatment depends on which treatment is used initially. If a
      clarithromycin-based regimen was used initially, a subsequent metronidazole-based
      treatment (quadruple therapy) may be used afterwards, and then a levofloxacin
      based combination would be a third "rescue" option. Alternatively, it has
      recently been suggested that levofloxacin-based rescue therapy constitutes an
      encouraging second-line strategy, representing an alternative to quadruple
      therapy in patients with previous PPI-clarithromycin-amoxicillin failure, with
      the advantage of efficacy, simplicity and safety. In this case, a quadruple
      regimen may be reserved as a third-line rescue option. Finally, rifabutin-based
      rescue therapy constitutes an encouraging empirical fourth-line strategy after
      multiple previous eradication failures with key antibiotics such as amoxicillin,
      clarithromycin, metronidazole, tetracycline, and levofloxacin. Even after two
      consecutive failures, several studies have demonstrated that H pylori eradication
      can finally be achieved in almost all patients if several rescue therapies are
      consecutively given. Therefore, the attitude in H pylori eradication therapy
      failure, even after two or more unsuccessful attempts, should be to fight and not
      to surrender.

PMID- 18803352
TI  - Biological impact of hepatitis B virus X-hepatitis C virus core fusion gene on
      human hepatocytes.
AB  - AIM: To investigate the biological impact of hepatitis B virus X- hepatitis C
      virus core (HBV X-HCV C) fusion gene on hepatoma cells. METHODS: The recombinant
      adenoviruses Ad-XC, Ad-X and Ad-C expressing HBV X-HCV C fusion gene, HBV X gene
      and HCV C gene were constructed, respectively. Hepatoma cells were infected with
      different recombinant adenoviruses. MTT, colony-forming experiment, FCM, TUNEL
      assay were performed to observe the biological impact of the HBV X-HCV C fusion
      gene on liver cells. RESULTS: MTT showed that the Ad-XC group cells grew faster
      than the other group cells. Colony-forming experiment showed that the colony
      forming rate for the Ad-XC group cells was significantly higher than that for the
      other group cells. FCM analysis showed that Ad-XC/Ad-X/Ad-C infection enhanced
      the progression of G1-->S phase in the HepG2 cell cycle. The apoptosis index of
      the Ad-XC, Ad-X, Ad-C group cells was significantly lower than that of the Ad0
      and control group cells. Semi-quantitative RT-PCR showed that the expression
      level of c-myc was the highest in Ad-XC infected cells. Tumor formation was found
      at the injected site of mice inoculated with Ad-XC-infected LO2 cells, but not in
      control mice. CONCLUSION: Ad-XC, Ad-X and Ad-C facilitate the proliferation
      activity of HepG2 cells and inhibit their apoptosis in vitro. The effect of Ad-XC
      is significantly stronger than that of Ad-X and Ad-C. Up-regulation of c-myc may
      be one of the mechanisms underlying the synergism of HBV X and HCV C genes on
      hepatocarcinogenesis in athymic nude mice.

PMID- 18803353
TI  - Liver insulin-like growth factor 2 methylation in hepatitis C virus cirrhosis and
      further occurrence of hepatocellular carcinoma.
AB  - AIM: To assess the predictive value of the insulin-like growth factor 2 (Igf2)
      methylation profile for the occurrence of Hepatocellular Carcinoma (HCC) in
      hepatitis C (HCV) cirrhosis. METHODS: Patients with: (1) biopsy-proven
      compensated HCV cirrhosis; (2) available baseline frozen liver sample; (3)
      absence of detectable HCC; (4) regular screening for HCC; (5) informed consent
      for genetic analysis were studied. After DNA extraction from liver samples and
      bisulfite treatment, unbiased PCR and DHPLC analysis were performed for
      methylation analysis at the Igf2 locus. The predictive value of the Igf2
      methylation profile for HCC was assessed by Kaplan-Meier and Cox methods.
      RESULTS: Among 94 included patients, 20 developed an HCC during follow-up (6.9 +/
      3.2 years). The methylation profile was hypomethylated, intermediate and
      hypermethylated in 13, 64 and 17 cases, respectively. In univariate analysis, two
      baseline parameters were associated with the occurrence of HCC: age (P = 0.01)
      and prothrombin (P = 0.04). The test of linear tendency between the three ordered
      levels of Igf2 methylation and probability of HCC occurrence was significant (Log
      Rank, P = 0.043; Breslow, P = 0.037; Tarone-Ware, P = 0.039). CONCLUSION: These
      results suggest that hypomethylation at the Igf2 locus in the liver could be
      predictive for HCC occurrence in HCV cirrhosis.

PMID- 18803354
TI  - Distribution of secretory inhibitor of platelet microbicidal protein among
      anaerobic bacteria isolated from stool of children with diarrhea.
AB  - AIM: To study the secretory inhibitor of platelet microbicidal protein (SIPMP)
      phenotypes of faecal anaerobic isolates from patients with diarrhea. METHODS:
      Faecal isolates of anaerobic bacteria (B. fragilis, n = 42; B. longum, n = 70; A.
      israelii, n = 21; E. lentum, n = 12) from children with diarrhea were tested.
      SIPMP production was tested by inhibition of platelet microbicidal protein (PMP)
      bioactivity against B. subtilis and was expressed as percentage of inhibition of
      PMP bactericidal activity. RESULTS: Among anaerobic isolates 80% of B. longum
      strains, 85.7% of A. israelii strains, 50% of E. lentum strains and 92.86% of B.
      fragilis strains were SIPMP-positive. The isolated anaerobic organisms
      demonstrated SIPMP production at a mean level of 13.8% +/- 0.7%, 14.7% +/- 1.8%,
      3.9% +/- 0.9% (P < 0.05) and 26.8% +/- 7.5% (P < 0.05) for bifidobacteria, A.
      israelii, E. lentum and B. fragilis, respectively. CONCLUSION: Data from the
      present study may have significant implications in understanding the pathogenesis
      of microecological disorders in the intestine, as well as for future improvement
      in the prevention and therapy of anaerobe-associated infections.

PMID- 18803355
TI  - Is there a role for Tc-99m (V) DMSA scintigraphy in ischemic colitis?
AB  - AIM: To evaluate the role of pentavalent Tc-99m dimercaptosuccinic acid [Tc-99m
      (V) DMSA] in the diagnosis of ischemic colitis. METHODS: Fourteen patients with
      endoscopically and histologically confirmed ischemic colitis were included in the
      study. Tc-99m (V) DMSA scintigraphy was performed within 2 d after colonoscopy.
      Images were considered positive when an area of increased activity was observed
      in the region of interest and negative when no abnormal tracer uptake was
      detected. RESULTS: In 3 out of the 14 patients, Tc-99m (V) DMSA images showed
      moderate activity in the bowel. The scintigraphic results corresponded with the
      endoscopic findings. In the other 11 patients, no abnormal tracer uptake was
      detected in the abdomen. CONCLUSION: Besides the limited number of patients, Tc
      99m (V) DMSA could not be considered as a useful imaging modality for the
      evaluation of ischemic colitis.

PMID- 18803356
TI  - Direct hemoperfusion with a polymyxin B-immobilized cartridge in intestinal warm
      ischemia reperfusion.
AB  - AIM: To investigate the effectiveness of direct hemoperfusion with polymyxin B
      immobilized fibers (DHP-PMX therapy) on warm ischemia-reperfusion (I/R) injury of
      the small intestine. METHODS: The proximal jejunum and distal ileum of mongrel
      dogs were resected. Warm ischemia was performed by clamping the superior
      mesenteric artery (SMA) and vein (SMV) for 2 h. Blood flow to the proximal small
      intestine was restored 1 h after reperfusion, and the distal small intestine was
      used as a stoma. The experiment was discontinued 6 h after reperfusion. The dogs
      were divided into two groups: the DHP-PMX group (n = 6, DHP-PMX was performed for
      180 min; from 10 min prior to reperfusion to 170 min after reperfusion) and the
      control group (n = 5). The rate pressure product (RPP), SMA blood flow, mucosal
      tissue blood flow, and intramucosal pH (pHi) were compared between the two
      groups. The serum interleukin (IL)-10 levels measured 170 min after reperfusion
      were also compared. RESULTS: The RPP at 6 h after reperfusion was significantly
      higher in the PMX group than in the control group (12 174 +/- 1832 mmHg/min vs
      8929 +/- 1797 mmHg/min, P < 0.05). The recovery rates of the SMA blood flow at 1
      and 6 h after reperfusion were significantly better in the PMX group than in the
      control group (61% +/- 7% vs 44% +/- 4%, P < 0.05, and 59% +/- 5% vs 35% +/- 5%,
      P < 0.05, respectively). The recovery rate of the mucosal tissue blood flow and
      the pHi levels at 6 h after reperfusion were significantly higher in the PMX
      group (61% +/- 8% vs 31% +/- 3%, P < 0.05 and 7.91 +/- 0.06 vs 7.69 +/- 0.08, P <
      0.05, respectively). In addition, the serum IL-10 levels just before DHP-PMX
      removal were significantly higher in the PMX group than in the control group (1
      569 +/- 253 pg/mL vs 211 +/- 40 pg/mL, P < 0.05). CONCLUSION: DHP-PMX therapy
      reduced warm I/R injury of the small intestine. IL-10 may play a role in
      inhibiting I/R injury during DHP-PMX therapy.

PMID- 18803357
TI  - Metabolic syndrome is associated with erosive esophagitis.
AB  - AIM: To clarify whether insulin resistance and metabolic syndrome are risk
      factors for erosive esophagitis. METHODS: A case-control study was performed
      using the database of the Kangbuk Samsung Hospital Medical Screening Center.
      RESULTS: A total of 1679 cases of erosive esophagitis and 3358 randomly selected
      controls were included. Metabolic syndrome was diagnosed in 21% of the cases and
      12% of the controls (P < 0.001). Multiple logistic regressions confirmed the
      association between erosive esophagitis and metabolic syndrome (Odds ratio, 1.25;
      95% CI, 1.04-1.49). Among the components of metabolic syndrome, increased waist
      circumference, elevated serum triglyceride levels and hypertension were
      significant risk factors for erosive esophagitis (all P < 0.01). Furthermore,
      increased insulin resistance (Odds ratio, 0.91; 95% CI, 0.85-0.98) and fatty
      liver, as diagnosed by ultrasonography (Odds ratio, 1.39; 95% CI, 1.20-1.60),
      were also related to erosive esophagitis even after adjustment for a series of
      confounding factors. CONCLUSION: Metabolic syndrome and increased insulin
      resistance are associated with an increased risk of developing erosive
      esophagitis.

PMID- 18803358
TI  - Clinical, virologic and phylogenetic features of hepatitis B infection in Iranian
      patients.
AB  - AIM: To characterize the clinical, serologic and virologic features of hepatitis
      B virus (HBV) infection in Iranian patients with different stages of liver
      disease. METHODS: Sixty two patients comprising of 12 inactive carriers, 30
      chronic hepatitis patients, 13 patients with liver cirrhosis and 7 patients with
      hepatocellular carcinoma (HCC) were enrolled in the study. The HBV S, C and basal
      core promoter (BCP) regions were amplified and sequenced, and the clinical,
      serologic, phylogenetic and virologic characteristics were investigated. RESULTS:
      The study group consisted of 16 HBeAg-positive and 46 HBeAg-negative patients.
      Anti-HBe-positive patients were older and had higher levels of ALT, ASL and
      bilirubin compared to HBeAg-positive patients. Phylogenetic analysis revealed
      that all patients were infected with genotype D (mostly ayw2). The G1896A precore
      (PC) mutant was detected in 58.1% patients. HBeAg-negative patients showed a
      higher rate of PC mutant compared to HBeAg-positive patients (c2 = 9.682, P =
      0.003). The majority of patients with HCC were HBeAg-negative and were infected
      with PC mutant variants. There was no significant difference in the occurrence of
      BCP mutation between the two groups, while the rate of BCP plus PC mutants was
      higher in HBeAg-negative patients (c2 = 4.308, P = 0.04). In the HBV S region,
      the genetic variability was low, and the marked substitution was P120T/S, with a
      rate of 9.7% (n = 6). CONCLUSION: In conclusion, HBV/D is the predominant
      genotype in Iran, and the nucleotide variability in the BCP and PC regions may
      play a role in HBV disease outcome in HBeAg-negative patients.

PMID- 18803359
TI  - Polymorphisms of microsomal triglyceride transfer protein in different hepatitis
      B virus-infected patients.
AB  - AIM: To identify the two polymorphisms of microsomal triglyceride transfer
      protein (MTP) gene in the Chinese population and to explore their correlation
      with both hepatitis B virus (HBV) self-limited infection and persistent
      infection. METHODS: A total of 316 subjects with self-limited HBV infection and
      316 patients with persistent HBV infection (195 subjects without familial
      history), matched with age and sex, from the Chinese Han population were enrolled
      in this study. Polymorphisms of MTP at the promoter region -493 and at H297Q were
      determined by the allele specific polymerase chain reaction (PCR). RESULTS: The
      ratio of males to females was 2.13:1 for each group and the average age in the
      self-limited and chronic infection groups was 38.36 and 38.28 years,
      respectively. None of the allelic distributions deviated significantly from that
      predicted by the Hardy-Weinberg equilibrium. There was a linkage disequilibrium
      between H297Q and -493G/T (D' = 0.77). As the c2 test was used, the genotype
      distribution of MTP-493G/T demonstrated a significant difference between the self
      limited infection group and the entire chronic group or the chronic patients with
      no family history (c2 = 8.543, P = 0.015 and c2 = 7.199, P = 0.019). The allele
      distribution at the MTP-493 position also demonstrated a significant difference
      between the study groups without family history (c2 = 6.212, P = 0.013). The T
      allele emerged as a possible protective factor which may influence the outcomes
      of HBV infection (OR: 0.59; 95% CI: 0.389-0.897). CONCLUSION: The polymorphism of
      the MTP gene, T allele at -493, may be involved in determining the HBV infection
      outcomes, of which the mechanism needs to be further investigated.

PMID- 18803360
TI  - Dendroaspis natriuretic peptide relaxes gastric antral circular smooth muscle of
      guinea-pig through the cGMP/cGMP-dependent protein kinase pathway.
AB  - AIM: To systematically investigate if cGMP/cGMP-dependent protein kinase G (PKG)
      signaling pathway may participate in dendroaspis natriuretic peptide (DNP)
      induced relaxation of gastric circular smooth muscle. METHODS: The content of
      cGMP in guinea pig gastric antral smooth muscle tissue and perfusion solution
      were measured using radioimmunoassay; spontaneous contraction of gastric antral
      circular muscles recorded using a 4-channel physiograph; and Ca(2+)-activated
      K(+) currents (I(K(Ca))) and spontaneous transient outward currents (STOCs) in
      isolated gastric antral myocytes were recorded using the whole-cell patch clamp
      technique. RESULTS: DNP markedly enhanced cGMP levels in gastric antral smooth
      muscle tissue and in the perfusion medium. DNP induced relaxation in gastric
      antral circular smooth muscle, which was inhibited by KT5823, a cGMP-dependent
      PKG inhibitor. DNP increased I(K(Ca)). This effect was almost completely blocked
      by KT5823, and partially blocked by LY83583, an inhibitor of guanylate cyclase to
      change the production of cGMP. DNP also increased STOCs. The effect of DNP on
      STOCs was abolished in the presence of KT5823, but not affected by KT-5720, a PKA
      specific inhibitor. CONCLUSION: DNP activates I(K(Ca)) and relaxes guinea-pig
      gastric antral circular smooth muscle via the cGMP/PKG-dependent singling axis
      instead of cAMP/PKA pathway.

PMID- 18803361
TI  - Recovery from respiratory failure after decompression laparotomy for severe acute
      pancreatitis.
AB  - We present three cases of patients (at the age of 56 years, 49 years and 74 years
      respectively) with severe acute pancreatitis (SAP), complicated by intra
      abdominal compartment syndrome (ACS) and respiratory insufficiency with
      limitations of mechanical ventilation. The respiratory situation of the patients
      was significantly improved after decompression laparotomy (DL) and lung
      protective ventilation was re-achieved. ACS was discussed followed by a short
      review of the literature. Our cases show that DL may help patients with SAP to
      recover from severe respiratory failure.

PMID- 18803362
TI  - Atypical presentation of pioderma gangrenosum complicating ulcerative colitis:
      rapid disappearance with methylprednisolone.
AB  - Pioderma gangrenosum (PG) is an uncommon ulcerative cutaneous dermatosis
      associated with a variety of systemic diseases, including inflammatory bowel
      disease (IBD), arthritis, leukaemia, hepatitis, and primary biliary cirrhosis.
      Other cutaneous ulceration resembling PG had been described in literature. There
      has been neither laboratory finding nor histological feature diagnostic of PG,
      and diagnosis of PG is mainly made based on the exclusion criteria. We present
      here a patient, with ulcerative colitis (UC) who was referred to the emergency
      section with a large and rapidly evolving cutaneous ulceration. Laboratory and
      microbiological investigation associated with histological findings of the ulcer
      specimen allowed us to exclude autoimmune and systemic diseases as well as immuno
      proliferative disorders. An atypical presentation of PG with UC was diagnosed.
      Pulse boluses of i.v. methyl-prednisolone were started, and after tapering
      steroids, complete resolution of the skin lesion was achieved in 3 wk. The
      unusual rapid healing of the skin ulceration with steroid mono-therapy and the
      atypical cutaneous presentation in this patient as well as the risk of
      misdiagnosis of PG in the clinical practice were discussed.

PMID- 18803363
TI  - Development of autoimmune hepatitis type 1 after pulsed methylprednisolone
      therapy for multiple sclerosis: a case report.
AB  - A 43-year-old woman with multiple sclerosis (MS) was treated with pulsed
      methylprednisolone and interferon beta at a hospital. Four weeks after initiating
      treatment, liver dysfunction occurred and she was referred and admitted to our
      hospital. Clinical and laboratory findings were consistent with and fulfilled the
      criteria for drug-induced hepatitis, but not for autoimmune hepatitis (AIH). She
      was successfully treated with corticosteroids. As ataxia developed after 1 year,
      she was treated with pulsed methylprednisolone for 3 d, then readmitted to our
      hospital when liver dysfunction occurred. Clinical and laboratory findings led to
      the diagnosis of AIH. To the best of our knowledge, this is the second case of
      AIH developed after pulsed methylprednisolone for MS.

PMID- 18803364
TI  - Acute pancreatitis successfully diagnosed by diffusion-weighted imaging: a case
      report.
AB  - Diffusion-weighted imaging (DWI) is an established diagnostic method of acute
      stroke. The latest advances in magnetic resonance imaging (MRI) technology have
      greatly expanded the utility of DWI in the examination of various organs. Recent
      studies have revealed the usefulness of DWI for imaging of the liver, kidney,
      ovary, and breast. We report a patient with acute pancreatitis detected by DWI
      and discussed the efficacy of DWI in diagnosing acute pancreatitis. A 50-year old
      man presented with a primary complaint of abdominal pain. We performed both DWI
      and computed tomography (CT) for this patient. The signal intensity in a series
      of DWI was measured and the apparent diffusion coefficient (ADC) values were
      calculated to differentiate inflammation from normal tissue. Two experienced
      radiologists evaluated the grade of acute pancreatitis by comparing the CT
      findings. Initially, the pancreas and multiple ascites around the pancreas
      produced a bright signal and ADC values were reduced on DWI. As the inflammation
      decreased, the bright signal faded to an iso-signal and the ADC values returned
      to their normal level. There was no difference in the abilities of DWI and CT
      images to detect acute pancreatitis. However, our case indicates that DWI can
      evaluate the manifestations of acute pancreatitis using no enhancement material
      and has the potential to replace CT as a primary diagnostic strategy for acute
      pancreatitis.

PMID- 18803365
TI  - Asymptomatic colonic metastases from primary squamous cell carcinoma of the lung
      with a positive fecal occult blood test.
AB  - We describe a 74-year-old man with a colonic metastatic squamous cell carcinoma
      (SCC) from the lung. His chest X-ray revealed an abnormal shadow in the right
      upper lobe. Computed tomography (CT) of the chest demonstrated a large lung tumor
      in the right upper lobe obstructing the right upper bronchus. Bronchoscopy
      revealed an easy-bleeding tumor in the right upper bronchus that was diagnosed as
      poorly differentiated squamous cell lung carcinoma. He underwent colonoscopy
      because he had a positive fecal occult blood test. Colonoscopy revealed a large
      protruding lesion with central ulceration in the descending colon. Histological
      examination of the biopsy specimen obtained from the colonic lesion revealed SCC.
      The lesion was diagnosed as metastatic colonic SCC. He had no abdominal symptoms.
      He underwent chemotherapy with an infusion of cisplatin 130 mg i.v. day 1, and
      docetaxel hydrate 100 mg i.v. day 1, repeated every 4 wk, followed by 4 courses
      of chemotherapy. The primary lesion shrank by less than 10% and was judged to be
      "Partial Response" (PR) after 3 courses of treatment. The patient still lived 23
      wk after the diagnosis of metastatic colonic SCC. Colonic metastasis of primary
      SCC of the lung is rare.

PMID- 18803368
TI  - Site-specific incorporation of chemical probes into proteins for NMR.
AB  - The ability to incorporate chemical probes into peptides is of great importance
      because it can render novel functionality to proteins and greatly expand our
      capacity to investigate complex biological systems. A methodology developed by
      the Schultz laboratory provides a unique strategy to incorporate chemical probes
      as unnatural amino acids into proteins by "expanding the genetic code" of the
      host cell. A recent application of this methodology that allows the site-specific
      incorporation of three NMR-active probes into proteins demonstrates the potential
      for researchers to explore avenues that are not easily achievable with existing
      methods.

PMID- 18803369
TI  - Folding on the assembly line.
AB  - Deciphering the mechanism of folding of newly synthesized proteins in the cell is
      a major challenge because of the large size and multiplicity of molecular
      components involved and the asynchrony of biosynthesis. Fluorescently labeled
      ribosome-bound nascent chains of a defined length were prepared and subjected to
      dynamic fluorescence depolarization spectroscopy measurements. Nanosecond
      anisotropy decay correlation times of proteins' nascent chains at different
      stages of polypeptide elongation were determined for the first time. Striking
      dependence of the chain dynamics on the stages of elongation was observed and
      revealed chain length dependence of folding on the ribosome.

PMID- 18803370
TI  - Modeling oral rat chronic toxicity.
AB  - The chronic toxicity is fundamental for toxicological risk assessment, but its
      correlation with the chemical structures has been studied only little. This is
      partly due to the complexity of such an experimental test that embraces a
      plethora of different biological effects and mechanisms of action, making (Q)SAR
      studies extremely challenging. In this paper we report a predictive in silico
      study of more than 400 compounds based on two-dimensional chemical descriptors
      and multivariate analysis. The root mean squared error of the predictive model is
      0.73 (in a logarithmic scale) on a leave-one-out cross-validation and is close to
      the estimated variability of experimental values (0.64). The analysis of the
      model revealed that the chronic toxicity effects are driven by the
      bioavailability of the compound that constitutes a baseline effect plus excess
      toxicity possible described by a few chemical moieties. The results obtained give
      confidence that this model can be useful for establishing a level of safety
      concern in the absence of hard toxicological data.

PMID- 18803371
TI  - Chemical Descriptors Library (CDL): a generic, open source software library for
      chemical informatics.
AB  - In this article the Chemical Descriptors Library (CDL), a generic, open source
      software library for chemical informatics is introduced. The library is written
      using standard-compliant C++ programming language. The CDL provides a generic
      interface for traversing the structure of a molecular graph and accessing its
      properties. As a result, the software offers flexibility, reusability, and
      maintainability. This interface has been used to develop several chemical
      informatics algorithms, including molecular text format parsers and writers;
      substructure, pharmacophore, and atom type fingerprints; and both common
      substructure search and SMARTS search. The algorithms are described and evaluated
      on 3 data sets comprising 1000, 50000, and 100000 small molecules, respectively.
      The properties of the algorithms in terms of complexity analysis and processing
      times are presented and discussed.

PMID- 18803372
TI  - Tuning emission properties of iridium and ruthenium metallosurfactants in
      micellar systems.
AB  - Ruthenium metallosurfactant forms micelles that show efficient electronic energy
      transfer processes in the presence of an analogous iridium complex. Modulation of
      the process is achieved upon incorporation of these amphiphiles into
      cetyltrimethylammonium bromide micelles, allowing a tuning of the two emissions.

PMID- 18803373
TI  - Iron(III) uptake and release by chrysobactin, a siderophore of the
      phytophatogenic bacterium Erwinia chrysanthemi.
AB  - The plant pathogenic enterobacterium Erwinia chrysanthemi causes important soft
      rot disease on a wide range of plants including vegetables and ornamentals of
      economic importance. It produces a major mono(catecholate) siderophore,
      chrysobactin (alpha-N-(2,3-dihydroxybenzoyl)-D-lysyl-L-serine). To unravel the
      role of chrysobactin in the virulence of E. chrysanthemi, its iron(III)
      coordination properties were thus investigated in aqueous solutions using
      electrospray ionization mass spectrometric, potentiometric, and
      spectrophotometric methods. Moreover, kinetic experiments allowed us to determine
      the uptake and release mechanisms. The formation mechanism of the 1:1 complex
      reveals a key role of the terminal carboxylic group of chrysobactin in the
      binding of either FeOH(2+) or Fe2(OH)2(4+). The proton-driven dissociation of the
      ferric tris-, bis-, and mono(chrysobactin) complexes was also studied. For these
      three ferric complexes, a single protonation triggers the release of the bound
      chrysobactin molecule. Interestingly, the dissociation of the last ligand
      proceeded via the formation of an intermediate for which a salicylate-type mode
      of bonding was proposed.

PMID- 18803374
TI  - Metallacarboranes as building blocks for polyanionic polyarmed aryl-ether
      materials.
AB  - Polyanionic species have been obtained in high yield by a new route in the ring
      opening reaction of cyclic oxonium [3,3'-Co(8-C4H8O2-1,2-C2B9H10)(1',2'-C2B9H11)]
      (2) by using carboxylic acids, Grignard reagents, and thiocarboranes as
      nucleophiles. The crystal structures of Na3(H2O)(C2H5OH)[1'',3'',5''-{3,3'-Co(8
      O(CH2CH2O)2-1,2-C2B9H10)(1',2'-C2B9H11)}3-C6H3] and Na(H2O)[3,3'-Co(8
      O(CH2CH2O)2C(O)CH3-1,2-C2B9H10)(1',2'-C2B9H11)] show that the chain contributes
      three or two oxygen atoms for coordination to Na(+), and interestingly, the [3,3'
      Co(1,2-C2B9H11)2](-) moiety provides extra B-H coordination sites. These B-H...Na
      interactions in the solid state have also been confirmed by dynamic NMR studies
      in solution. These new polyanionic compounds that contain multiple carborane or
      metallacarborane clusters at their periphery may prove useful as new classes of
      boron neutron capture therapy compounds with enhanced water solubility and as a
      core to make a new class of dendrimers.

PMID- 18803375
TI  - Boraguanidinates: synthesis, X-ray structures, and reactions of
      {Li2[(i)Pr2NB(NDipp)2]}2 with p-block and group 12 element halides.
AB  - The new Dipp-substituted boranes (Dipp = 2,6-diisopropylphenyl) (i)Pr2NB(NHDipp)2
      (5), BrB(NHDipp)2 (7b), and B(NHDipp)3 (8) have been prepared in high yields and
      characterized in solution by multinuclear NMR spectroscopy ((1)H, (11)B and
      (13)C) and in the solid state by X-ray crystallography. Reaction of 5 with 2
      equiv of (n)BuLi in n-hexane produces {Li2[(i)Pr2NB(NDipp)2]}2 (6) the first
      example of a stable dilithiated boraguanidinate. The unsolvated complex 6 has a
      dimeric structure in the solid state. A survey of the reactions of 6 with p-block
      and Group 12 element halides revealed various types of reactivity including (a)
      disproportionation (InCl), (b) reduction to the metal (PbCl2, CdCl2, TeBr4, TeI4,
      and TlCl), and (c) simple metathesis (GeCl2, MgCl2, and ZnCl2). The metathetical
      products were characterized by multinuclear NMR spectra but, in contrast to the
      dilithiated complex 6, they readily decompose in non-coordinating solvents to
      form the diprotonated compound 5.

PMID- 18803376
TI  - GaCl3-assisted cyclization reactions in
      hypersilyl(trimethylsilyl)aminodichlorophosphine.
AB  - Hypersilyl(trimethylsilyl)aminodichlorophosphine, (hyp)N(SiMe3)PCl2, was treated
      with GaCl3, which resulted in the formation of an interesting novel bicycle,
      composed of a four-membered SiNP2 ring and a five-membered P2Ga2Cl ring. In the
      presence of Me3SiN3, the same reaction provided access to a cyclo-2-phospha-4
      sila-1,3-diazenium tetrachlorogallate. The free chloro-cyclo-phosphasiladiazane
      was obtained by the addition of nucleophilic bases.

PMID- 18803379
TI  - Multiplexed multicolor Raman imaging of live cells with isotopically modified
      single walled carbon nanotubes.
AB  - We show that single walled carbon nanotubes (SWNTs) with different isotope
      compositions exhibit distinct Raman G-band peaks and can be used for multiplexed
      multicolor Raman imaging of biological systems. Cancer cells with specific
      receptors are selectively labeled with three differently "colored" SWNTs
      conjugated with various targeting ligands including Herceptin (anti-Her2),
      Erbitux (anti-Her1), and RGD peptide, allowing for multicolor Raman imaging of
      cells in a multiplexed manner. SWNT Raman signals are highly robust against
      photobleaching, allowing long-term imaging and tracking. With narrow peak
      features, SWNT Raman signals are easily differentiated from the autofluorescence
      background. The SWNT Raman excitation and scattering photons are in the near
      infrared region, which is the most transparent optical window for biological
      systems in vitro and in vivo. Thus, SWNTs are novel Raman tags promising for
      multiplexed biological detection and imaging.

PMID- 18803381
TI  - From N-alkylimidazole ligands at a rhenium center: ring opening or formation of
      NHC complexes.
AB  - Cationic rhenium tricarbonyl complexes with three N-alkylimidazole ligands
      undergo deprotonation of the central CH group upon reaction with 1 equiv of
      KN(SiMe3)2. For the tris(N-methylimidazole) complex, the metal fragment shifts
      from N to C, leaving an NHC complex with a nonsubstituted N atom. For compounds
      with at least one N-mesitylimidazole ligand, the intramolecular attack of the
      deprotonated carbon onto the central carbon of an N-mesitylimidazole ligand
      results in ring opening of the latter.

PMID- 18803382
TI  - Fluorine substituted adenosines as probes of nucleobase protonation in functional
      RNAs.
AB  - Ionized nucleobases are required for folding, conformational switching, or
      catalysis in a number of functional RNAs. A common strategy to study these sites
      employs nucleoside analogues with perturbed pKa, but the interpretation of these
      studies is often complicated by the chemical modification introduced, in
      particular modifications that add, remove, or translocate hydrogen bonding groups
      in addition to perturbing pKa values. In the present study we present a series of
      fluorine substituted adenosine analogues that produce large changes in N1 pKa
      values with minimal structural perturbation. These analogues include fluorine for
      hydrogen substitutions in the adenine ring of adenosine and 7-deaza-adenosine
      with resulting N1 pKa values spanning more than 4 pKa units. To demonstrate the
      utility of these analogues we have conducted a nucleotide analogue interference
      mapping (NAIM) study on a self-ligating construct of the Varkud Satellite (VS)
      ribozyme. We find that each of the analogues is readily incorporated by T7 RNA
      polymerase and produces fully active transcripts when substituted at the majority
      of sites. Strong interferences are observed for three sites known to be critical
      for VS ribozyme function, most notably A756. Substitutions at A756 lead to slight
      enhancements in activity for elevated pKa analogues and dramatic interferences in
      activity for reduced pKa analogues, supporting the proposed catalytic role for
      this base. The structural similarity of these analogues, combined with their even
      incorporation and selective interference, provides an improved method for
      identifying sites of adenosine protonation in a variety of systems.

PMID- 18803383
TI  - Self-assembly of alpha-helical coiled coil nanofibers.
AB  - The alpha-helical coiled coil is one of the best-studied and most well-understood
      protein folding motifs. In particular, the coiled coil can be made to self
      assemble into a nanofibrous architecture with many potential applications in
      biomimetic engineering and elsewhere. The key to the assembly of such nanofibers
      has been the formation of "sticky ended" dimers through careful selection of
      electrostatically charged amino acids. In this work, we demonstrate for the first
      time that sticky ended dimers are not a prerequisite for alpha-helical coiled
      coil nanofiber formation. In contrast, we show that blunt-ended dimers are able
      to form nanofibers with a uniform diameter of 4 nm while being hundreds of
      nanometers in length. Furthermore, the length and lateral packing can be
      controlled through selection of amino acids not involved in the coiled coil
      interface.

PMID- 18803384
TI  - Water phase transition induced by a Stone-Wales defect in a boron nitride
      nanotube.
AB  - Boron nitride nanotubes (BNNTs) have been reported to possess superior water
      permeation properties. In this work, using molecular dynamics simulations with
      partial charges, capturing BNNT polarization effects obtained from quantum
      calculations, we found that Stone-Wales (SW) defects in a (5,5) BNNT result in
      phase transition of water, i.e., a transition between liquid-like phase and vapor
      like phase was observed. The 90 degree rotation of the B-N bond, SW
      transformation, in an SW-defective (5,5) BNNT results in breaking of hydrogen
      bonding with neighboring water molecules and leads to the existence of a vapor
      like phase near the SW defect. Water transport rate was evaluated by measuring
      translocation time. Water in an SW-defective (5,5) BNNT has fewer translocation
      events, longer translocation time, and a higher axial diffusion coefficient
      compared to water in a nondefective (5,5) BNNT.

PMID- 18803385
TI  - Expeditious chemoenzymatic synthesis of homogeneous N-glycoproteins carrying
      defined oligosaccharide ligands.
AB  - An efficient chemoenzymatic method for the construction of homogeneous N
      glycoproteins was described that explores the transglycosylation activity of the
      endo-beta-N-acetylglucosaminidase from Arthrobacter protophormiae (Endo-A) with
      synthetic sugar oxazolines as the donor substrates. First, an array of large
      oligosaccharide oxazolines were synthesized and evaluated as substrates for the
      Endo-A-catalyzed transglycosylation by use of ribonuclease B as a model system.
      The experimental results showed that Endo-A could tolerate modifications at the
      outer mannose residues of the Man3GlcNAc-oxazoline core, thus allowing
      introduction of large oligosaccharide ligands into a protein and meanwhile
      preserving the natural, core N-pentasaccharide (Man3GlcNAc2) structure in the
      resulting glycoprotein upon transglycosylation. In addition to ligands for
      galectins and mannose-binding lectins, azido functionality could be readily
      introduced at the N-pentasaccharide (Man3GlcNAc2) core by use of azido-containing
      Man3GlcNAc oxazoline as the donor substrate. The introduction of azido
      functionality permits further site-specific modifications of the resulting
      glycoproteins, as demonstrated by the successful attachment of two copies of
      alphaGal epitopes to ribonuclease B. This study reveals a broad substrate
      specificity of Endo-A for transglycosylation, and the chemoenzymatic method
      described here points to a new avenue for quick access to various homogeneous N
      glycoproteins for structure-activity relationship studies and for biomedical
      applications.

PMID- 18803386
TI  - Rhodium-catalyzed hydroformylation of cyclopropenes.
AB  - The first catalytic diastereo- and enantioselective hydroformylation of
      cyclopropenes was demonstrated. The reaction proceeds efficiently under very mild
      conditions and low catalyst loadings providing high yields of
      cyclopropylcarboxaldehydes. This novel methodology represents a convenient, atom
      economic approach toward optically active cyclopropylcarboxaldehydes from readily
      available prochiral cyclopropenes.

PMID- 18803387
TI  - Highly stable organic monolayers for reacting silicon with further
      functionalities: the effect of the C-C bond nearest the silicon surface.
AB  - Crystalline Si(111) surfaces have been alkylated in a two-step
      chlorination/alkylation process using various organic molecules having similar
      backbones but differing in their C-C bond closest to the silicon surface (i.e., C
      C vs C=C vs C[triple bond]C bonds). X-ray photoelectron spectroscopic (XPS) data
      show that functionalization of silicon surfaces with propenyl magnesium bromide
      (CH3-CH=CH-MgBr) organic molecules gives nearly full coverage of the silicon atop
      sites, as on methyl- and propynyl-terminated silicon surfaces. Propenyl
      terminated silicon surface shows less surface oxidation and is more robust
      against solvent attacks when compared to methyl- and propynyl-terminated silicon
      surfaces. We also show a secondary functionalization process of propenyl
      terminated silicon surface with 4'-[3-Trifluoromethyl-3H-diazirin-3-yl]-benzoic
      acid N-hydroxysuccinimide ester [TDBA-OSu] cross-linker. The Si-CH=CH-CH3
      surfaces thus offer a means of attaching a variety of chemical moieties to a
      silicon surface through a short linking group, enabling applications in molecular
      electronics, energy conversion, catalysis, and sensing.

PMID- 18803388
TI  - From a paramagnetic, mononuclear supersulfidonickel(II) complex to a diamagnetic
      dimer with a four-sulfur two-electron bond.
AB  - The first isolable "side-on" supersulfidonickel(II) complex 1(1) with the elusive
      S2-. ligand has been synthesized by facile oxidation of the corresponding
      nickel(I) precursor [LNi] with elemental sulfur. Remarkably, paramagnetic 1(1)
      associates voluntarily to give the diamagnetic dimer 1(2) with a four-sulfur two
      electron bond as proven by X-ray diffraction analysis, spectroscopic measurements
      (1H NMR, EPR, SQUID), and DFT calculations. Gentle sulfur transfer of 1(1) to
      Ph3P or its reaction with [LNi] affords solely the genuine disulfide complex 3
      having a Ni2(mu-mu2:mu2-S2) core.

PMID- 18803389
TI  - Interfacial charge recombination between e(-)-TiO2 and the I(-)/I3(-) electrolyte
      in ruthenium heteroleptic complexes: dye molecular structure-open circuit voltage
      relationship.
AB  - A series of heteroleptic ruthenium(II) polypyridyl complexes containing
      phenanthroline ligands have been designed, synthesized, and characterized. The
      spectroscopic and electrochemical properties of the complexes have been studied
      in solution and adsorbed onto semiconductor nanocrystalline metal oxide
      particles. The results show that for two of the ruthenium complexes, bearing
      electron-donating (-NH2) or electron-withdrawing (-NO2) groups, the presence of
      the redox-active I(-)/I3(-) electrolyte produces important changes in the
      interfacial charge transfer processes that limit the device performance. For
      example, those dyes enhanced the electron recombination reaction between the
      photoinjected electrons at TiO2 and the oxidized redox electrolyte. In an effort
      to understand the details of such striking observations, we have monitored the
      charge transfer reactions taking place at the different interfaces of the devices
      using time-resolved single photon counting, laser transient spectroscopy, and
      light-induced photovoltage measurements.

PMID- 18803390
TI  - Aluminum-induced cell wall peroxidase activity and lignin synthesis are
      differentially regulated by jasmonate and nitric oxide.
AB  - Cassia tora is an annual legume and cultivated as a traditional medicinal herb
      for multiple therapies including regulation of blood pressure and blood lipid.
      Because of naturally occurring acidic soils in southeastern China, this plant
      species may possess strategies for tolerance to low pH and aluminum toxicity. In
      the search for the regulatory basis of biochemical response to Al, cell wall
      bound peroxidases, including lignin-generated peroxidases and NADH oxidases, were
      investigated in the root tips of C. tora. Activities of both types of peroxidases
      significantly increased with Al concentrations. Analysis with native PAGE also
      demonstrated the strong induction of cell wall peroxidases by Al. The Al-induced
      increasing activities of peroxidases were closely correlated with lignin
      accumulation and H 2O 2 production. The biochemical effect of exogenous nitric
      oxide (NO) and methyl jasmonic acid (MJ) was examined to investigate signal
      properties and lignin synthesis under Al stress. Application of MJ at 10 microM
      promoted root sensitivity to Al by activating apoplastic peroxidase activity and
      accumulating H 2O 2 and lignin, whereas the opposite action was found for NO. The
      sensitivity of apoplastic peroxidases under Al stress was associated with the
      cross-talk of MJ and NO signals. The analysis reveals that the activity of
      lipoxygenase (an enzyme for MJ biosynthesis), with its transcripts increased in
      Al-exposed roots, was depressed by NO exposure. The effect of MJ on intracellular
      NO production was also investigated. It is shown that NO staining with 4,5
      diaminofluorescein diacetate fluorescence was intensified by Al but was
      suppressed by MJ. These results suggest that NO and MJ may interplay in signaling
      the cell wall peroxidase activity and lignin synthesis in the roots exposed to
      Al.

PMID- 18803391
TI  - Isolation and characterization of an extracellular antimicrobial protein from
      Aspergillus oryzae.
AB  - A 17 kDa antimicrobial protein was isolated from growth medium containing the
      filamentous fungus Aspergillus oryzae by extracting the supernatants from the
      culture media, ion exchange chromatography on CM-sepharose, and C18 reverse-phase
      high-performance liquid chromatography. This antimicrobial protein, which we
      considered to be an extracellular antimicrobial protein from A. oryzae (exAP
      AO17), possessed antimicrobial activity but lacked hemolytic activity. The exAP
      AO17 protein strongly inhibited pathogenic microbial strains, including
      pathogenic fungi, Fusarium moniliform var. subglutinans and Colletotrichum
      coccodes, and showed antibacterial activity against bacteria, including E. coli
      O157 and Staphylococcus aureus. To confirm that the protein acts as a regulation
      factor for extracellular secretion, we examined growth under varying conditions
      of N sources, C sources, ions, ambient pH, and stress. Various culture conditions
      were found to induce characteristic changes in the expression of protein
      synthesis as analyzed by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis. Highly basic polypeptides were regulated by suppressing the
      ambient pH under acidic conditions and strongly induced under alkaline
      conditions, thus confirming that pH regulation is physiologically relevant. The
      expression of exAP-AO17 was upregulated by heat shock upon growth in the presence
      of NaCl. Automated Edman degradation showed that the N-terminal sequence of exAP
      AO17 was NH 2-GLPGPAGAVGFAGKDQNM-. ExAP-AO17 showed partial sequence homology
      with a collagen belonging to the animal source. These results suggest that exAP
      AO17 is an excellent candidate as a lead compound for the development of novel
      oral or other types of anti-infective agents.

PMID- 18803392
TI  - trans-C18:1 isomers in cheeses enriched in unsaturated fatty acids and
      manufactured with different milk fat globule sizes.
AB  - Increasing the knowledge on dietary fat composition, mainly the minor components,
      will improve the nutritional value of foods and their labeling. In this study, we
      examined the trans-octadecenoic acid (C18:1) composition of Emmental cheeses
      enriched in unsaturated fatty acids (FA) and manufactured with milks produced by
      cows selected to produce small and large fat globules. The FA composition of the
      milks was not significantly ( P > 0.05) different from the FA composition of the
      corresponding Emmental cheeses. Increasing the unsaturated FA content of the
      cheeses using dietary manipulations lead to an increase in the trans-C18:1 and
      changed their isomeric profiles. In milk fat produced with the linseed-enriched
      diet, the trans-10 C18:1 concentration was greater than trans-11 C18:1 (vaccenic
      acid), which is classically the major trans-C18:1 in milk fat. The content in
      trans-C18:1 and more particularly in trans-10 C18:1 was negatively correlated
      with the size of fat globules ( r (2) = 0. 82 and 0.87, respectively) and related
      to milk fat depression. The trans-C18:1 content was negatively correlated with
      the saturated FA (slope = -0.35; r (2) = 0.81) and positively correlated with the
      unsaturated (slope = 0.29; r (2) = 0.85) and monounsaturated (slope = 0.32; r (2)
      = 0.81) FA. Focusing on the health-related considerations of fat in food
      products, further nutritional studies are needed to elucidate the role of trans
      C18:1 isomers.

PMID- 18803393
TI  - Selection of aptamers against live bacterial cells.
AB  - Single-stranded DNA or RNA aptamer molecules have usually been selected against
      purified target molecules. To eliminate the need of purifying target molecules on
      the cell surface, we have developed a selection technique using live bacterial
      cells in suspension as targets, to select for ssDNA aptamers specific to cell
      surface molecules. Lactobacillus acidophilus cells were chosen to demonstrate
      proof of principle based on their high abundance of surface molecules (potential
      targets). Aptamer pools obtained after 6-8 rounds of selection demonstrated high
      affinity for and selective binding with L. acidophilus cells when tested via flow
      cytometry, microscopy, and fluorescence measurements. Out of 27 aptamers that
      were cloned and sequenced, one sequence, hemag1P, was found to bind to L.
      acidophilus much more strongly and specifically than other cells tested. This
      aptamer was predicted to have a tight hairpin secondary structure. On average, an
      estimated 164 +/- 47 aptamer molecules were bound to a target cell with an
      apparent K d of 13 +/- 3 nM. A likely putative molecular target of hemag1P is the
      S-layer protein on the cell surface.

PMID- 18803394
TI  - Quartz resonator-based approach to ultrasonic rheology of a mixed-phase micellar
      system.
AB  - We report the application of a quartz crystal microbalance with dissipation
      monitoring (QCM-D) to rheology of mixed-phase micellar systems. This novel
      application of QCM-D allows for the facile monitoring of complex systems under a
      variety of conditions. Viscosity measurements were obtained for sodium dodecyl
      sulfate (SDS) solutions, ranging from 1.0 to 50.0 mg/mL, in the presence and
      absence of toluene. Toluene was shown to swell SDS micelles as observed through
      an increase in viscosity, and an inflection point designating the critical
      micelle concentration (CMC) was clearly visible. Aqueous SDS solutions were also
      stabilized with sodium chloride (NaCl), up to 1.2 M, and with n-dodecanol in
      toluene solutions, up to 5.0 vol %. Rodlike micelle formation and swelling with
      toluene were observed in both cases, supporting previous studies. These studies
      show that a QCM-D approach to ultrasonic rheology holds potential for the
      specific study of multiphase systems, non-Newtonian fluids, and low volumes of
      analyte, aspects highly useful for complex or expensive colloidal dispersions
      such as micellar or biomolecular solutions.

PMID- 18803395
TI  - Electrospray-assisted laser desorption/ionization mass spectrometry for
      continuously monitoring the states of ongoing chemical reactions in organic or
      aqueous solution under ambient conditions.
AB  - Electrospray-assisted laser desorption/ionization (ELDI) combined with mass
      spectrometry allows chemical and biochemical compounds to be characterized
      directly from hydrophilic and hydrophobic organic solutions mixed with carbon
      powders under ambient conditions. Organic and inorganic compounds dissolved in
      polar or nonpolar solvent such as methanol, tetrahydrofuran, ethyl acetate,
      toluene, dichloromethane, or hexane can be detected using this ambient ionization
      technique without prior pretreatment. We have used this technique to monitor the
      progress in several ongoing reactions: the epoxidation of chalcone in ethanol,
      the chelation of ethylenediaminetetraacetic acid with copper and nickel ions in
      aqueous solution, the chelation of 1,10-phenanthroline with iron(II) in methanol,
      and the tryptic digestion of cytochrome c in aqueous solution. Liquid-ELDI
      analyses simply require irradiation of the surface of the sample solution with a
      pulsed ultraviolet laser; the laser energy is adsorbed by the carbon powder
      presuspended in the sample solution; the absorbed laser energy is then
      transferred to the surrounding solvent and to the analyte molecules in the
      solution, leading to their desorption; the desorbed gaseous analyte molecules are
      then postionized within an electrospray (ESI) plume to generate ESI-like analyte
      ions.

PMID- 18803396
TI  - Identification of phosphorylation-induced changes in vimentin intermediate
      filaments by site-directed spin labeling and electron paramagnetic resonance.
AB  - Phosphorylation drives the disassembly of the vimentin intermediate filament (IF)
      cytoskeleton at mitosis. Chromatographic analysis has suggested that
      phosphorylation produces a soluble vimentin tetramer, but little has been
      determined about the structural changes that are caused by phosphorylation or the
      structure of the resulting tetramer. In this study, site-directed spin labeling
      and electron paramagnetic resonance (SDSL-EPR) were used to examine the
      structural changes resulting from protein kinase A phosphorylation of vimentin
      IFs in vitro. EPR spectra suggest that the tetrameric species resulting from
      phosphorylation is the A11 configuration. EPR spectra also establish that the
      greatest degree of structural change was found in the linker 2 and the C-terminal
      half of the rod domain, despite the fact that most phosphorylation occurs in the
      N-terminal head domain. The phosphorylation-induced changes notably affected the
      proposed "trigger sequences" located in the linker 2 region, which have been
      hypothesized to mediate the induction of coiled-coil formation. These data are
      the first to document specific changes in IF structure resulting from a
      physiologic regulatory mechanism and provide further evidence, also generated by
      SDSL-EPR, that the linker regions play a key role in IF structure and regulation
      of assembly/disassembly.

PMID- 18803397
TI  - Characterization of quinolinate synthases from Escherichia coli, Mycobacterium
      tuberculosis, and Pyrococcus horikoshii indicates that [4Fe-4S] clusters are
      common cofactors throughout this class of enzymes.
AB  - Quinolinate synthase (NadA) catalyzes a unique condensation reaction between
      iminoaspartate and dihydroxyacetone phosphate, affording quinolinic acid, a
      central intermediate in the biosynthesis of nicotinamide adenine dinucleotide
      (NAD). Iminoaspartate is generated via the action of l-aspartate oxidase (NadB),
      which catalyzes the first step in the biosynthesis of NAD in most prokaryotes.
      NadA from Escherichia coli was hypothesized to contain an iron-sulfur cluster as
      early as 1991, because of its observed labile activity, especially in the
      presence of hyperbaric oxygen, and because its primary structure contained a
      CXXCXXC motif, which is commonly found in the [4Fe-4S] ferredoxin class of iron
      sulfur (Fe/S) proteins. Indeed, using analytical methods in concert with
      Mossbauer and electron paramagnetic resonance spectroscopies, the protein was
      later shown to harbor a [4Fe-4S] cluster. Recently, the X-ray structure of NadA
      from Pyrococcus horikoshii was solved to 2.0 A resolution [Sakuraba, H., Tsuge,
      H.,Yoneda, K., Katunuma, N., and Ohshima, T. (2005) J. Biol. Chem. 280, 26645
      26648]. This protein does not contain a CXXCXXC motif, and no Fe/S cluster was
      observed in the structure or even mentioned in the report. Moreover, rates of
      quinolinic acid production were reported to be 2.2 micromol min (-1) mg (-1),
      significantly greater than that of E. coli NadA containing an Fe/S cluster (0.10
      micromol min (-1) mg (-1)), suggesting that the [4Fe-4S] cluster of E. coli NadA
      may not be necessary for catalysis. In the study described herein, nadA genes
      from both Mycobacterium tuberculosis and Pyrococcus horikoshii were cloned, and
      their protein products shown to contain [4Fe-4S] clusters that are absolutely
      required for activity despite the absence of a CXXCXXC motif in their primary
      structures. Moreover, E. coli NadA, which contains nine cysteine residues, is
      shown to require only three for turnover (C113, C200, and C297), of which only
      C297 resides in the CXXCXXC motif. These results are consistent with a
      bioinformatics analysis of NadA sequences, which indicates that three cysteines
      are strictly conserved across all species. This study concludes that all
      currently annotated quinolinate synthases harbor a [4Fe-4S] cluster, that the
      crystal structure reported by Sakuraba et al. does not accurately represent the
      active site of the protein, and that the "activity" reported does not correspond
      to quinolinate formation.

PMID- 18803398
TI  - Functional role of transmembrane helix 6 in drug binding and transport by the ABC
      transporter MsbA.
AB  - The ATP-binding cassette transporter MsbA in Gram-negative bacteria can transport
      antibiotics and toxic ions. However, the key functional regions in MsbA which
      determine substrate specificity remain to be identified. We recently examined
      published mutations in the human MsbA homologue ABCB1 that alter multidrug
      transport in cells and identified mutations that affect the specificity for
      individual substrates (termed change-in-specificity mutations). When superimposed
      on the corrected 3.7 A resolution crystal structure of homodimeric MsbA from S
      almonella typhimurium, these change-in-specificity mutations colocalize in a
      major groove in each of the two "wings" of transmembrane helices (TMHs) that
      point away from one another toward the periplasm. Near the apex of the groove,
      the periplasmic side of TMH 6 in both monomers contains a hotspot of change-in
      specificity mutations and residues which, when replaced with cysteines in ABCB1,
      covalently interact with thiol-reactive drug analogues. We tested the importance
      of this region of TMH 6 for drug-protein interactions in Escherichia coli MsbA.
      In particular, we focused on conserved S289 and S290 residues in the hotspot.
      Their simultaneous replacement with alanine (termed the SASA mutant)
      significantly reduced the level of binding and transport of ethidium and Taxol by
      MsbA, whereas the interactions with Hoechst 33342 and erythromycin remained
      unaffected. Hence, the SASA mutation is associated with a change-in-specificity
      phenotype analogous to that of the change-in-specificity mutations in ABCB1. This
      study demonstrates for the first time the significance of TMH 6 for drug binding
      and transport by MsbA. Based on these data, a possible mechanism for alternating
      access of drug-binding surfaces in MsbA is discussed.

PMID- 18803399
TI  - Structural characterization of binding of Cu(II) to tau protein.
AB  - Transition metals have been frequently recognized as risk factors in
      neurodegenerative disorders, and brain lesions associated with Alzheimer's
      disease are rich in Fe(III), Zn(II), and Cu(II). By using different biophysical
      techniques (nuclear magnetic resonance, circular dichroism, light scattering, and
      microcalorimetry), we have structurally characterized the binding of Cu(II) to a
      198 amino acid fragment of the protein Tau that can mimic both the aggregation
      behavior and microtubule binding properties of the full-length protein. We
      demonstrate that Tau can specifically bind one Cu(II) ion per monomer with a
      dissociation constant in the micromolar range, an affinity comparable to the
      binding of Cu(II) to other proteins involved in neurodegenerative diseases. NMR
      spectroscopy showed that two short stretches of residues, (287)VQSKCGS (293) and
      (310)YKPVDLSKVTSKCGS (324), are primarily involved in copper binding, in
      agreement with mutational analysis. According to circular dichroism and NMR
      spectroscopy, Tau remains largely disordered upon binding to Cu(II), although a
      limited amount of aggregation is induced.

PMID- 18803400
TI  - Structure of the S100A6 complex with a fragment from the C-terminal domain of
      Siah-1 interacting protein: a novel mode for S100 protein target recognition.
AB  - S100A6 is a member of the S100 subfamily of EF-hand Ca (2+) binding proteins that
      has been shown to interact with calcyclin binding protein/Siah-1 interacting
      protein (CacyBP/SIP or SIP), a subunit of an SCF-like E3 ubiquitin ligase complex
      (SCF-TBL1) formed under genotoxic stress. SIP serves as a scaffold in this
      complex, linking the E2-recruiting module Siah-1 to the substrate-recruiting
      module Skp1-TBL1. A cell-based functional assay suggests that S100A6 modulates
      the activity of SCF-TBL1. The results from the cell-based experiments could be
      enhanced if it were possible to selectively inhibit S100A6-SIP interactions
      without perturbing any other functions of the two proteins. To this end, the
      structure of the S100A6-SIP complex was determined in solution by NMR and the
      strength of the interaction was characterized by isothermal titration
      calorimetry. In an initial step, the minimal S100A6 binding region in SIP was
      mapped to a 31-residue fragment (Ser189-Arg219) in the C-terminal domain. The
      structure of the S100A6-SIP(189-219) complex revealed that SIP(189-219) forms two
      helices, the first of which (Met193-Tyr200) interacts with S100A6 in a canonical
      binding mode. The second helix (Met207-Val216) lies over the S100A6 dimer
      interface, a mode of binding to S100A6 that has not previously been observed for
      any target bound to an S100 protein. A series of structure-based SIP mutations
      showed reduced S100A6 binding affinity, setting the stage for direct functional
      analysis of S100A6-SIP interactions.

PMID- 18803401
TI  - Mutations in the fourth EGF-like domain affect thrombomodulin-induced changes in
      the active site of thrombin.
AB  - A number of alanine and more conservative mutants of residues in the fourth
      domain of thrombomodulin (TM) were prepared and assayed for protein C activation
      and for thrombin binding. Several of the alanine mutations appeared to cause
      misfolding or structural defects as assessed by poor expression and/or NMR HSQC
      experiments, while more conservative mutations at the same site appeared to allow
      correct folding and preserved activity. Several of the conservative mutants bound
      more weakly to thrombin despite the fact that the fourth domain does not directly
      contact thrombin in the crystal structure of the thrombin-TM complex. A few of
      the mutant TM fragments bound thrombin with an affinity similar to that of the
      wild type but exhibited decreases in k cat for protein C activation. These
      mutants were also less able to cause a change in the steady state fluorescence of
      fluorescein-EGR-chloromethylketone bound to the active site of thrombin. These
      results suggest that some residues within the fourth domain of TM may primarily
      interact with protein C but others are functionally important for altering the
      way TM interacts with thrombin. Residues in the fourth domain that primarily
      affect k cat for protein C activation may do this by changing the active site of
      thrombin.

PMID- 18803402
TI  - The dilated cardiomyopathy G159D mutation in cardiac troponin C weakens the
      anchoring interaction with troponin I.
AB  - NMR spectroscopy has been employed to elucidate the molecular consequences of the
      DCM G159D mutation on the structure and dynamics of troponin C, and its
      interaction with troponin I (TnI). Since the molecular effects of human mutations
      are often subtle, all NMR experiments were conducted as direct side-by-side
      comparisons of the wild-type C-domain of troponin C (cCTnC) and the mutant
      protein, G159D. With the mutation, the affinity toward the anchoring region of
      cTnI (cTnI 34-71) was reduced ( K D = 3.0 +/- 0.6 microM) compared to that of the
      wild type ( K D < 1 microM). Overall, the structure and dynamics of the
      G159D.cTnI 34-71 complex were very similar to those of the cCTnC.cTnI 34-71
      complex. There were, however, significant changes in the (1)H, (13)C, and (15)N
      NMR chemical shifts, especially for the residues in direct contact with cTnI 34
      71, and the changes in NOE connectivity patterns between the G159D.cTnI 34-71 and
      cCTnC.cTnI 34-71 complexes. Thus, the most parsimonious hypothesis is that the
      development of disease results from the poor anchoring of cTnI to cCTnC, with the
      resulting increase in the level of acto-myosin inhibition in agreement with
      physiological data. Another possibility is that long-range electrostatic
      interactions affect the binding of the inhibitory and switch regions of cTnI
      (cTnI 128-147 and cTnI 147-163) and/or the cardiac specific N-terminus of cTnI
      (cTnI 1-29) to the N-domain of cTnC. These important interactions are all
      spatially close in the X-ray structure of the cardiac TnC core.

PMID- 18803403
TI  - Repair of O6-G-alkyl-O6-G interstrand cross-links by human O6-alkylguanine-DNA
      alkyltransferase.
AB  - O (6)-Alkylguanine-DNA alkyltransferase (AGT) plays an important role by
      protecting cells from alkylating agents. This reduces the frequency of
      carcinogenesis and mutagenesis initiated by such agents, but AGT also provides a
      major resistance mechanism to some chemotherapeutic drugs. To improve our
      understanding of the AGT-mediated repair reaction and our understanding of the
      spectrum of repairable damage, we have studied the ability of AGT to repair
      interstrand cross-link DNA damage where the two DNA strands are joined via the
      guanine- O (6) in each strand. An oligodeoxyribonucleotide containing a heptane
      cross-link was repaired with initial formation of an AGT-oligo complex and
      further reaction of a second AGT molecule yielding a hAGT dimer and free oligo.
      However, an oligodeoxyribonucleotide with a butane cross-link was a very poor
      substrate for AGT-mediated repair, and only the first reaction that forms an AGT
      oligo complex could be detected. Models of the reaction of these substrates in
      the AGT active site show that the DNA duplex is forced apart locally to repair
      the first guanine. This reaction is greatly hindered with the butane cross-link,
      which is mostly buried in the active site pocket and limited in conformational
      flexibility. This limitation also prevents the adoption of a conformation for the
      second reaction to repair the AGT-oligo complex. These results are consistent
      with the postulated mechanism of AGT repair that involves DNA binding and
      flipping of the substrate nucleotide and indicate that hAGT can repair some types
      of interstrand cross-link damage.

PMID- 18803404
TI  - Endoplasmic reticulum glucosidase II is inhibited by its end products.
AB  - The calnexin/calreticulin cycle is a quality control system responsible for
      promoting the folding of newly synthesized glycoproteins entering the endoplasmic
      reticulum (ER). The association of calnexin and calreticulin with the
      glycoproteins is regulated by ER glucosidase II, which hydrolyzes Glc 2Man X
      GlcNAc 2 glycans to Glc 1Man X GlcNAc 2 and further to Glc 0Man X GlcNAc 2 ( X
      represents any number between 5 and 9). To gain new insights into the reaction
      mechanism of glucosidase II, we developed a kinetic model that describes the
      interactions between glucosidase II, calnexin/calreticulin, and the glycans. Our
      model accurately reconstructed the hydrolysis of glycans with nine mannose
      residues and glycans with seven mannose residues, as measured by Totani et al.
      [Totani, K., Ihara, Y., Matsuo, I., and Ito, Y. (2006) J. Biol. Chem. 281, 31502
      31508]. Intriguingly, our model predicted that glucosidase II was inhibited by
      its nonglucosylated end products, where the inhibitory effect of Glc 0Man 7GlcNAc
      2 was much stronger than that of Glc 0Man 9GlcNAc 2. These predictions were
      confirmed experimentally. Moreover, our model suggested that glycans with a
      different number of mannose residues can be equivalent substrates of glucosidase
      II, in contrast to what had been previously thought. We discuss the possibility
      that nonglucosylated glycans, existing in the ER, might regulate the entry of
      newly synthesized glycoproteins into the calnexin/calreticulin cycle. Our model
      also shows that glucosidase II does not interact with monoglucosylated glycans
      while they are bound to calnexin or calreticulin.

PMID- 18803405
TI  - The evolutionarily conserved arrangement of domains in SRC family kinases is
      important for substrate recognition.
AB  - The SH3-SH2-kinase domain arrangement in nonreceptor tyrosine kinases has been
      conserved throughout evolution. For Src family kinases, the relative positions of
      the domains are important for enzyme regulation; they permit the assembly of Src
      kinases into autoinhibited conformations. The SH3 and SH2 domains of Src family
      kinases have an additional role in determining the substrate specificity of the
      kinase. We addressed the question of whether the domain arrangement of Src family
      kinases has a role in substrate specificity by producing mutants with alternative
      arrangements. Our results suggest that changes in the positions of domains can
      lead to specific changes in the phosphorylation of Sam68 and Cas by Src.
      Phosphorylation of Cas by several mutants triggers downstream signaling leading
      to cell migration. The placement of the SH2 domain with respect to the catalytic
      domain of Src appears to be especially important for proper substrate
      recognition, while the placement of the SH3 domain is more flexible. The results
      suggest that the involvement of the SH3 and SH2 domains in substrate recognition
      is one reason for the strict conservation of the SH3-SH2-kinase architecture.

PMID- 18803406
TI  - Interaction of metallothionein-2 with platinum-modified 5'-guanosine
      monophosphate and DNA.
AB  - Human metallothioneins (MTs), a family of cysteine- and metal-rich
      metalloproteins, play an important role in the acquired resistance to platinum
      drugs. MTs occur in the cytosol and the nucleus of the cells and sequester
      platinum drugs through interaction with their zinc-thiolate clusters. Herein, we
      investigate the ability of human Zn 7MT-2 to form DNA-Pt-MT cross-links using the
      cisplatin- and transplatin-modified plasmid DNA pSP73. Immunochemical analysis of
      MT-2 showed that the monofunctional platinum-DNA adducts formed DNA- cis/ trans
      Pt-MT cross-links and that platinated MT-2 was released from the DNA- trans-Pt-MT
      cross-links with time. The DNA- cis/ trans-Pt-MT cross-links were also formed in
      the presence of 2 mM glutathione, a strong S-donor ligand. Independently, we used
      5'-guanosine monophosphate (5'-GMP) platinated at the N7 position as a model of
      monofunctional platinum-DNA adducts. Comparison of reaction kinetics revealed
      that the formation of ternary complexes between Zn 7MT-2 and cis-Pt-GMP was
      faster than that of the trans isomer. The analysis of the reaction products with
      time showed that while the formation of ternary GMP- trans-Pt-MT complex(es) is
      accompanied by 5'-GMP release, a stable ternary GMP- cis-Pt-MT complex is formed.
      In the latter complex, a fast initial formation of two Pt-S bonds was followed by
      a slow formation of an additional Pt-S bond yielding an unusual Pt(II)S 3N
      coordination with N7-GMP as the only N-donor ligand. The ejection of negligible
      zinc from the zinc-thiolate clusters implies the initial formation of Zn-(mu
      SCys)-Pt bridges involving the terminal thiolate ligands. The biological
      implications of these studies are discussed.

PMID- 18803407
TI  - Electron transfer complex between nitrous oxide reductase and cytochrome c552
      from Pseudomonas nautica: kinetic, nuclear magnetic resonance, and docking
      studies.
AB  - The multicopper enzyme nitrous oxide reductase (N 2OR) catalyzes the final step
      of denitrification, the two-electron reduction of N 2O to N 2. This enzyme is a
      functional homodimer containing two different multicopper sites: CuA and CuZ. CuA
      is a binuclear copper site that transfers electrons to the tetranuclear copper
      sulfide CuZ, the catalytic site. In this study, Pseudomonas nautica cytochrome c
      552 was identified as the physiological electron donor. The kinetic data show
      differences when physiological and artificial electron donors are compared
      [cytochrome vs methylviologen (MV)]. In the presence of cytochrome c 552, the
      reaction rate is dependent on the ET reaction and independent of the N 2O
      concentration. With MV, electron donation is faster than substrate reduction.
      From the study of cytochrome c 552 concentration dependence, we estimate the
      following kinetic parameters: K m c 552 = 50.2 +/- 9.0 muM and V max c 552 = 1.8
      +/- 0.6 units/mg. The N 2O concentration dependence indicates a K mN 2 O of 14.0
      +/- 2.9 muM using MV as the electron donor. The pH effect on the kinetic
      parameters is different when MV or cytochrome c 552 is used as the electron donor
      (p K a = 6.6 or 8.3, respectively). The kinetic study also revealed the
      hydrophobic nature of the interaction, and direct electron transfer studies
      showed that CuA is the center that receives electrons from the physiological
      electron donor. The formation of the electron transfer complex was observed by
      (1)H NMR protein-protein titrations and was modeled with a molecular docking
      program (BiGGER). The proposed docked complexes corroborated the ET studies
      giving a large number of solutions in which cytochrome c 552 is placed near a
      hydrophobic patch located around the CuA center.

PMID- 18803408
TI  - E113 is required for the efficient photoisomerization of the unprotonated
      chromophore in a UV-absorbing visual pigment.
AB  - Protonation of the retinal Schiff base chromophore is responsible for the
      absorption of visible light and is stabilized by the counterion residue E113 in
      vertebrate visual pigments. However, this residue is also conserved in vertebrate
      UV-absorbing visual pigments (UV pigments) which have an unprotonated Schiff base
      chromophore. To elucidate the role played by this residue in the
      photoisomerization of the unprotonated chromophore in UV pigments, we measured
      the quantum yield of the E113Q mutant of the mouse UV cone pigment (mouse UV).
      The quantum yield of the mutant was much lower than that of the wild type,
      indicating that E113 is required for the efficient photoisomerization of the
      unprotonated chromophore in mouse UV. Introduction of the E113Q mutation into the
      chicken violet cone pigment (chicken violet), which has a protonated chromophore,
      caused deprotonation of the chromophore and a reduction in the quantum yield. On
      the other hand, the S90C mutation in chicken violet, which deprotonated the
      chromophore with E113 remaining intact, did not significantly affect the quantum
      yield. These results suggest that E113 facilitates photoisomerization in both UV
      absorbing and visible light-absorbing visual pigments and provide a possible
      explanation for the complete conservation of E113 among vertebrate UV pigments.

PMID- 18803409
TI  - Side-on end-on bound dinitrogen: an activated bonding mode that facilitates
      functionalizing molecular nitrogen.
AB  - Molecular nitrogen is the source of all of the nitrogen necessary to sustain life
      on this planet. How it is incorporated into the biosphere is complicated by its
      intrinsic inertness. For example, biological nitrogen fixation takes N(2) and
      converts it into ammonia using various nitrogenase enzymes, whereas industrial
      nitrogen fixation converts N(2) and H(2) to NH(3) using heterogeneous iron or
      ruthenium surfaces. In both cases, the processes are energy-intensive. Is it
      possible to discover a homogeneous catalyst that can convert molecular nitrogen
      into higher-value organonitrogen compounds using a less energy-intensive pathway?
      If this could be achieved, it would be considered a major breakthrough in this
      area. In contrast to carbon monoxide, which is reactive and an important
      feedstock in many homogeneous catalytic reactions, the isoelectronic but inert
      N(2) molecule is a very poor ligand and not a common industrial feedstock, except
      for the above-mentioned industrial production of NH(3). Because N(2) is readily
      available from the atmosphere and because nitrogen is an essential element for
      the biosphere, attempts to discover new processes involving this simple small
      molecule have occupied chemists for over a century. Since the first discovery of
      a dinitrogen complex in 1965, inorganic chemists have been key players in this
      area and have contributed much fundamental knowledge on structures, binding
      modes, and reactivity patterns. For the most part, the synthesis of dinitrogen
      complexes relies on the use of reducing agents to generate an electron-rich
      intermediate that can interact with this rather inert molecule. In this Account,
      a facile reaction of dinitrogen with a ditantalum tetrahydride species to
      generate the unusual side-on end-on bound N(2) moiety is described. This
      particular process is one of a growing number of new, milder ways to generate
      dinitrogen complexes. Furthermore, the resulting dinitrogen complex undergoes a
      number of reactions that expand the known patterns of reactivity for coordinated
      N(2). This Account reviews the reactions of ([NPN]Ta)(2)(mu-H)(2)(mu
      eta(1):eta(2)-N(2)), 2 (where NPN = PhP(CH(2)SiMe(2)NPh)(2)), with a variety of
      simple hydride reagents, E-H (where E-H = R(2)BH, R(2)AlH, RSiH(3), and
      Cp(2)ZrCl(H)), each of which results in the cleavage of the N-N bond to form
      various functionalized imide and nitride moieties. This work is described in the
      context of a possible catalytic cycle that in principle could generate higher
      value nitrogen-containing materials and regenerate the starting ditantalum
      tetrahydride. How this fails for each particular reagent is discussed and
      evaluated.

PMID- 18803410
TI  - Pyramids: a platform for designing multifunctional plasmonic particles.
AB  - This Account explores nanofabricated pyramids, a new class of nanoparticles with
      tunable optical properties at visible and near-infrared wavelengths. This system
      is ideally suited for designing multifunctional plasmonic materials for use in
      diagnostics, imaging, sensing, and therapeutics. The nanofabrication scheme that
      we developed (called PEEL) for these asymmetric metal particles is extremely
      versatile and offers several advantages over synthetic methodologies. The PEEL
      approach yields pyramids with variable sizes, thicknesses, and multimetal
      compositions, as well as blunt or ultrasharp tips or no tips. In addition, we
      have prepared pyramids with site-specific chemical and biological functionality
      on different portions of the pyramids. This is an important design feature for
      biological applications, as suggested by the generation of amphiphilic gold
      pyramids functionalized with alkanethiols on the hydrophobic portions and DNA on
      the hydrophilic portions. The optical characteristics of these pyramids depend on
      particle orientation, wavevector direction, and polarization direction and can be
      tuned. Using the multipolar surface plasmon resonances of large (>250 nm)
      pyramids, imaging and spectral identification of pyramid orientation in condensed
      media was possible. We were also able to direct pyramids to assemble into one-
      and two-dimensional arrays with interesting optical properties. Furthermore,
      modification of the PEEL fabrication scheme allowed the production of
      multimaterial pyramidal structures with complex attributes, highlighting the
      power of this platform for exacting nanometer-scale control over particle
      structure and composition.

PMID- 18803411
TI  - Adsorption and structural change of beta-lactoglobulin at the diacylglycerol
      water interface.
AB  - Diacylglycerol (DAG)/water and triacylglycerol (TAG)/water emulsions were
      prepared using beta-lactoglobulin (beta-LG) as an emulsifier. The oil phase (20%
      in emulsion) was mixed with beta-LG solution (1% beta-LG in water, pH 7) to
      prepare the emulsions. A fine oil-in-water emulsion was produced from both DAG
      and TAG oils. The interfacial protein concentration of the TAG emulsion was
      higher than that of the DAG emulsion. The zeta potential of the DAG oil droplet
      was higher than that of the TAG oil droplet. The front-surface fluorescence
      spectroscopy results revealed that tryptophan residues in beta-LG moved to the
      more hydrophobic environment during the adsorption of protein on the oil droplet
      surfaces. Changes in secondary structure of beta-LG during the adsorption were
      determined by FT-IR spectroscopy. Decreases in the beta-sheet content concomitant
      with increases in the alpha-helix content were observed during the adsorption to
      the oil droplets, and the degree of structural change was greater for beta-LG in
      the TAG emulsion than in the DAG emulsion, indicating the increased unfolding of
      adsorbed beta-LG on the TAG oil droplet surface. Results of interfacial tension
      measurement supported this speculation, that is, the increased unfolding of the
      protein at the TAG-water interface. Trypsin- and proteinase K-catalyzed
      proteolysis was used to probe the topography of the adsorbed beta-LG on the oil
      droplet surface. SDS-PAGE analyses of liberated peptides after the proteolysis
      indicated the higher susceptibility of beta-LG adsorbed on the DAG oil droplet
      surface than on the TAG oil droplet surface. On the basis of all the results, we
      discussed the conformation of the adsorbed beta-LG on the two oil droplet
      surfaces.

PMID- 18803412
TI  - Novel peptide linkers for highly potent antibody-auristatin conjugate.
AB  - Auristatins are highly potent antimitotic agents that have received considerable
      attention because of their activities when targeted to tumor cells in the form of
      antibody-drug conjugates (ADCs). Our lead agent, SGN-35, consists of the cAC10
      antibody linked to the N-terminal amino acid of monomethylauristatin E (MMAE) via
      a valine-citrulline p-aminobenzylcarbamate (val-cit-PABC) linker that is cleaved
      by intracellular proteases such as cathepsin B. More recently, we developed an
      auristatin F (AF) derivative monomethylauristatin F (MMAF), which unlike MMAE
      contains the amino acid phenylalanine at the C-terminal position. Because of the
      negatively charged C-terminal residue, the potency of AF and MMAF is impaired.
      However, their ability to kill target cells is greatly enhanced through
      facilitated cellular uptake by internalizing mAbs. Here, we explore the effects
      of linker technology on AF-based ADC potency, activity, and tolerability by
      generating a diverse set of dipeptide linkers between the C-terminal residue and
      the mAb carrier. The resulting ADCs differed widely in activity, with some having
      significantly improved therapeutic indices compared to the original mAb-Val-Cit
      PABC-MMAF conjugate. The therapeutic index was increased yet further by
      generating dipeptide-based ADCs utilizing new auristatins with methionine or
      tryptophan as the C-terminal drug residue. These results demonstrate that
      manipulation of the C-terminal peptide sequence used to attach auristatins to the
      mAb carrier can lead to highly potent and specific conjugates with greatly
      improved therapeutic windows.

PMID- 18803413
TI  - Selectins ligand decorated drug carriers for activated endothelial cell
      targeting.
AB  - New active particulate polymeric vectors based on branched polyester copolymers
      of hydroxy-acid and allyl glycidyl ether were developed to target drugs to the
      inflammatory endothelial cell surface. The hydroxyl and carboxyl derivatives of
      these polymers allow grafting of ligand molecules on the polyester backbones at
      different densities. A known potent nonselective selectin ligand was selected and
      synthesized using a new scheme. This synthesis allowed the grafting of the ligand
      to the polyester polymers, preserving its binding activity as assessed by docking
      simulations. Selectin expression on human umbilical cord vascular endothelial
      cells (HUVEC) was induced with the pro-inflammatory bacterial lipopolysaccharide
      (LPS) or with the nonselective inhibitor of nitric oxide synthase L-NAME. Strong
      adhesion of the ligand decorated nanoparticles was evidenced in vitro on
      activated HUVEC. Binding of nanoparticles bearing ligand molecules could be
      efficiently inhibited by prior incubation of cells with free ligand,
      demonstrating that adhesion of the nanoparticles is mediated by specific
      interaction between the ligand and the selectin receptors. These nanoparticles
      could be used for specific drug delivery to the activated vascular endothelium,
      suggesting their application in the treatment of diseases with an inflammatory
      component such as rheumatoid arthritis and cancer.

PMID- 18803415
TI  - N,N,N',N'-tetramethylchloroformamidinium hexafluorophosphate (TCFH), a powerful
      coupling reagent for bioconjugation.
AB  - Prodrugs are increasingly used as delivery vehicles for pharmaceutical agents
      that present solubility and/or pharmacokinetic/metabolic issues. In the course of
      the development of prodrugs for the antitumoral agent thiocoraline, standard
      coupling reagents and procedures failed to provide the desired target derivatives
      because of the lack of reactivity of its quinolinic alcohol. In contrast, the use
      of N,N,N',N'-tetramethylchloroformamidinium hexafluorophosphate (TCFH) resulted
      in good yields of ester prodrugs of thiocoraline and could be applicable to other
      drugs with similar limitations.

PMID- 18803414
TI  - Cell-permeable MR contrast agents with increased intracellular retention.
AB  - Magnetic resonance imaging (MRI) is a technique used in both clinical and
      experimental settings to produce high-resolution images of opaque organisms
      without ionizing radiation. Currently, MR imaging is augmented by contrast
      agents, and the vast majority these small molecule Gd(III) chelates are confined
      to the extracellular regions. As a result, contrast agents are confined to
      vascular regions reducing their ability to provide information about cell
      physiology or molecular pathology. We have shown that polypeptides of arginine
      have the capacity to transport Gd(III) contrast agents across cell membranes.
      However, this transport is not unidirectional, and once inside the cell, the
      arginine-modified contrast agents efflux rapidly, decreasing the intracellular
      Gd(III) concentration and corresponding MR image intensity. By exploiting the
      inherent disulfide reducing environment of cells, thiol compounds, Gd(III)-DOTA
      SS-Arg 8 and Gd(III)-DTPA-SS-Arg 8, are cleaved from their cell-penetrating
      peptide transduction domains upon cell internalization. This reaction prolongs
      the cell-associated lifetime of the chelated Gd(III) by cleaving it from the cell
      transduction domain.

PMID- 18803416
TI  - Protein expression profile of the mouse metaphase-II oocyte.
AB  - The mature oocyte contains the full complement of maternal proteins required for
      fertilization, the transition to zygotic transcription, and the beginning stages
      of embryogenesis. Many of these proteins have yet to be characterized. In this
      study, two-dimensional electrophoresis (2-DE) of mouse metaphase-II (MII) oocyte
      proteins, stained with silver staining or Pro-Q Diamond dye, was performed to
      describe the proteome and phosphoproteome of the mouse oocyte derived from ICR
      mice. A total of 869 selected protein spots, corresponding to 380 unique
      proteins, were identified successfully by mass spectrometry, in which 90 protein
      spots representing 53 unique proteins have been stained with Pro-Q Diamond,
      indicating that they are in phosphorylated forms. All identified proteins were
      bioinformatically annotated in detail and compared with the embryonic stem cell
      (ESC) proteome. A proteome reference database for the mouse oocyte was
      established from the protein data generated in this study, which can be accessed
      over the Internet ( http://reprod.njmu.edu.cn/2d). This database is the most
      detailed mouse oocyte proteomic database to date. It should be valuable in
      expanding our knowledge of the regulation of signaling in oogenesis,
      fertilization, and embryo development, while revealing potential mechanisms for
      epigenetic reprogramming.

PMID- 18803417
TI  - High quality catalog of proteotypic peptides from human heart.
AB  - Proteomics research is beginning to expand beyond the more traditional shotgun
      analysis of protein mixtures to include targeted analyses of specific proteins
      using mass spectrometry. Integral to the development of a robust assay based on
      targeted mass spectrometry is prior knowledge of which peptides provide an
      accurate and sensitive proxy of the originating gene product (i.e., proteotypic
      peptides). To develop a catalog of "proteotypic peptides" in human heart, TRIzol
      extracts of left-ventricular tissue from nonfailing and failing human heart
      explants were optimized for shotgun proteomic analysis using Multidimensional
      Protein Identification Technology (MudPIT). Ten replicate MudPIT analyses were
      performed on each tissue sample and resulted in the identification of 30 605
      unique peptides with a q-value < or = 0.01, corresponding to 7138 unique human
      heart proteins. Experimental observation frequencies were assessed and used to
      select over 4476 proteotypic peptides for 2558 heart proteins. This human cardiac
      data set can serve as a public reference to guide the selection of proteotypic
      peptides for future targeted mass spectrometry experiments monitoring potential
      protein biomarkers of human heart diseases.

PMID- 18803418
TI  - Poly(ether-ester) conjugates with enhanced degradation.
AB  - When a linear or a four arm star-shaped polyglycidol is used as macroinitiator,
      densely grafted poly(glycidol-graft-epsilon-caprolactone) and poly(glycidol-graft
      L-lactide) and loosely grafted poly[(glycidol-graft-epsilon-caprolactone)-co
      glycidol] copolymers have been synthesized by chemical or, in the latter case, by
      enzymatic catalyzed ring-opening polymerization of epsilon-caprolactone and L
      lactide. The well-defined copolymers possess similar molecular weights, but
      differ in their architecture, microstructure and chemical composition. The
      hydrolytic degradation behavior was studied in a phosphate buffer solution at pH
      7.4 and 37 degrees C for up to 90 days. After different time periods, the mass
      loss was determined and the degraded copolymers were analyzed by means of NMR,
      size exclusion chromatography, and scanning electron microscopy. Compared to
      linear poly(epsilon-caprolactone), poly[(glycidol-graft-epsilon-caprolactone)-co
      glycidol] shows a change of the degradation mechanism and a tremendous
      enhancement of polymer degradation. As this effect is attributed to the high
      concentration of hydroxy groups at the polyglycidol backbone, this work points
      out a new possibility to tailor the degradation profiles of polyesters by the
      introduction of functionality into the polymeric material.

PMID- 18803419
TI  - Nanofibers made of globular proteins.
AB  - Strong nanofibers composed entirely of a model globular protein, namely, bovine
      serum albumin (BSA), were produced by electrospinning directly from a BSA
      solution without the use of chemical cross-linkers. Control of the spinnability
      and the mechanical properties of the produced nanofibers was achieved by
      manipulating the protein conformation, protein aggregation, and
      intra/intermolecular disulfide bonds exchange. In this manner, a low-viscosity
      globular protein solution could be modified into a polymer-like spinnable
      solution and easily spun into fibers whose mechanical properties were as good as
      those of natural fibers made of fibrous protein. We demonstrate here that newly
      formed disulfide bonds (intra/intermolecular) have a dominant role in both the
      formation of the nanofibers and in providing them with superior mechanical
      properties. Our approach to engineer proteins into biocompatible fibrous
      structures may be used in a wide range of biomedical applications such as
      suturing, wound dressing, and wound closure.

PMID- 18803420
TI  - Base controlled polydiazeniumdiolation of 4-heptanone and a new water layer
      structure.
AB  - In a stoichiometry-controlled reaction, nitric oxide adds to the enolate of 4
      heptanone at ca. -23 degrees C to give mono-, bis-, or tris-diazeniumdiolate (
      N2O2(-)) products: potassium 4-heptanone-3,3,5-tris(diazeniumdiolate) (1),
      potassium butanoate 2,2-bis(diazeniumdiolate) (2), and potassium butanoate 2
      diazeniumdiolate (3). The diazeniumdiolate products are stable crystalline solids
      under ambient conditions and as solids exothermally decompose at high
      temperatures. Single-crystal X-ray data measured for the dihydrate 3 reveal a new
      layer aggregation, L4(4)8(8), as octameric water aggregates in a stair
      conformation which interacts minimally with the cation of the salt.

PMID- 18803421
TI  - Myxochromide B3, a new member of the myxochromide family of secondary
      metabolites.
AB  - Myxochromides are cyclic depsipeptides with an unsaturated polyketide side chain,
      which have been reported from different myxobacterial species, e.g., Myxococcus
      xanthus and Stigmatella aurantiaca. To date, myxochromides are subdivided into
      the groups A and S, according to their peptidic core structure. The peptide
      moiety of the new myxochromide B3 (1), which was isolated from a myxobacterial
      strain of the genus Myxococcus, differs from that of myxochromides A and S.
      Compound 1 thus is the first representative of a new group of myxochromides. For
      myxochromide A3 (2) the complete and assigned spectroscopic data are described.
      For the structure elucidation one- and two-dimensional NMR spectroscopy as well
      as mass spectrometry have been applied. Configurational analysis has been
      accomplished by chiral GC-MS and HPLC.

PMID- 18803422
TI  - Encapsulation of semiconducting polymers in vault protein cages.
AB  - We demonstrate that a semiconducting polymer [poly(2-methoxy-5-propyloxy
      sulfonate phenylene vinylene), MPS-PPV] can be encapsulated inside recombinant,
      self-assembling protein nanocapsules called "vaults". Polymer incorporation into
      these nanosized protein cages, found naturally at approximately 10,000 copies per
      human cell, was confirmed by fluorescence spectroscopy and small-angle X-ray
      scattering. Although vault cellular functions and gating mechanisms remain
      unknown, their large internal volume and natural prevalence within the human body
      suggests they could be used as carriers for therapeutics and medical imaging
      reagents. This study provides the groundwork for the use of vaults in
      encapsulation and delivery applications.

PMID- 18803423
TI  - Reversible pH lability of cross-linked vault nanocapsules.
AB  - Vaults are ubiquitous, self-assembled protein nanocapsules with dimension in the
      sub-100 nm range that are conserved across diverse phyla from worms to humans.
      Their normal presence in humans at a copy number of over 10,000/cell makes them
      attractive as potential drug delivery vehicles. Toward this goal, bifunctional
      amine-reactive reagents are shown to be useful for the reversible cross-linking
      of recombinant vaults such that they may be closed and opened in a controllable
      manner.

PMID- 18803424
TI  - Quantum-interference-controlled molecular electronics.
AB  - Quantum interference in coherent transport through single molecular rings may
      provide a mechanism to control the current in molecular electronics. We
      investigate its applicability, using a single-particle Green function method
      combined with ab initio electronic structure calculations. We find that the
      quantum interference effect (QIE) is strongly dependent on the interaction
      between molecular pi-states and contact sigma-states. It is masked by sigma
      tunneling in small molecular rings with Au leads, such as benzene, due to strong
      pi-sigma hybridization, while it is preserved in large rings, such as
      [18]annulene, which then could be used to realize quantum interference effect
      (QIE) transistors.

PMID- 18803425
TI  - Clinical application of array-based comparative genomic hybridization for the
      identification of prognostically important genetic alterations in chronic
      lymphocytic leukemia.
AB  - Genomic aberrations have increasingly gained attention as prognostic markers in B
      cell chronic lymphocytic leukemia (CLL). Fluorescence in situ hybridization
      (FISH) has improved the detection rate of genomic alterations in CLL from
      approximately 50% using conventional cytogenetics to greater than 80%. More
      recently, array comparative genomic hybridization (CGH) has gained popularity as
      a clinical tool that can be applied to detect genomic gains and losses of
      prognostic importance in CLL. Array CGH and FISH are particularly useful in CLL
      because genomic gains and losses are key events with both biologic and prognostic
      significance, while balanced translocations have limited prognostic value.
      Although FISH has a higher technical sensitivity, it requires separate, targeted
      hybridizations for the detection of alterations at genomic loci of interest.
      Array CGH, on the other hand, has the ability to provide a genome-wide survey of
      genomic aberrations with a single hybridization reaction. Array CGH is expanding
      the known genomic regions of importance in CLL and allows these regions to be
      evaluated in the context of a genome-wide perspective. Ongoing clinical trials
      are evaluating the use of genomic aberrations as tools for risk-stratifying
      patients for therapy, thus increasing the need for reliable and high-yield
      methods to detect these genomic changes. In this review, we consider the use of
      array CGH as a clinical tool for the identification of genomic alterations with
      prognostic significance in CLL, and suggest ways to integrate this test into the
      clinical molecular diagnostic laboratory work flow.

PMID- 18803426
TI  - Molecular signatures of cardiovascular disease risk: potential for test
      development and clinical application.
AB  - Most cardiovascular diseases are multifactorial by etiology. As an example, the
      development of myocardial infarction is promoted by numerous risk factors,
      ranging from rather modifiable lifestyle habits (e.g. smoking, physical activity)
      to genetic predisposition. With respect to the latter, 15 years of candidate gene
      analyses have failed to explain the molecular basis for the genetic
      predisposition to myocardial infarction. By contrast, recent genome-wide
      association studies have identified chromosomal loci that reproducibly displayed
      some association with myocardial infarction risk. When molecular genetic studies
      of coronary artery disease were first begun, it was assumed that genetic factors
      would soon be routinely incorporated into risk prediction scores. A number of
      biomarkers have been identified and tested in combination with the classical risk
      factors for refined risk prediction. However, the strategy for individualized
      risk prediction by incorporation of new biomarkers in established scores has so
      far proven to be more difficult than at first hoped.

PMID- 18803427
TI  - Celiac disease: risk assessment, diagnosis, and monitoring.
AB  - Celiac disease is an autoimmune disorder occurring in genetically susceptible
      individuals, triggered by gluten and related prolamins. Well identified
      haplotypes in the human leukocyte antigen (HLA) class II region (either DQ2
      [DQA*0501-DQB*0201] or DQ8 [DQA*0301-DQB1*0302]) confer a large part of the
      genetic susceptibility to celiac disease.Celiac disease originates as a result of
      a combined action involving both adaptive and innate immunity. The adaptive
      immune response to gluten has been well described, with the identification of
      specific peptide sequences demonstrating HLA-DQ2 or -DQ8 restrictive binding
      motifs across various gluten proteins. As for innate immunity, through specific
      natural killer receptors expressed on their surface, intra-epithelial lymphocytes
      recognize nonclassical major histocompatibility complex (MHC)-I molecules such as
      MICA, which are induced on the surface of enterocytes by stress and inflammation,
      and this interaction leads to their activation to become lymphokine-activated
      killing cells. Four possible presentations of celiac disease are recognized: (i)
      typical, characterized mostly by gastrointestinal signs and symptoms; (ii)
      atypical or extraintestinal, where gastrointestinal signs/symptoms are minimal or
      absent and a number of other manifestations are present; (iii) silent, where the
      small intestinal mucosa is damaged and celiac disease autoimmunity can be
      detected by serology, but there are no symptoms; and, finally, (iv) latent, where
      individuals possess genetic compatibility with celiac disease and may also show
      positive autoimmune serology, that have a normal mucosa morphology and may or may
      not be symptomatic.The diagnosis of celiac disease still rests on the
      demonstration of changes in the histology of the small intestinal mucosa. The
      classic celiac lesion occurs in the proximal small intestine with histologic
      changes of villous atrophy, crypt hyperplasia, and increased intraepithelial
      lymphocytosis. Currently, serological screening tests are utilized primarily to
      identify those individuals in need of a diagnostic endoscopic biopsy. The serum
      levels of immunoglobulin (Ig)A anti-tissue transglutaminase (or TG2) are the
      first choice in screening for celiac disease, displaying the highest levels of
      sensitivity (up to 98%) and specificity (around 96%). Anti-endomysium antibodies
      IgA (EMA), on the other hand, have close to 100% specificity and a sensitivity of
      greater than 90%. The interplay between gliadin peptides and TG2 is responsible
      for the generation of novel antigenic epitopes, the TG2-generated deamidated
      gliadin peptides. Such peptides represent much more celiac disease-specific
      epitopes than native peptides, and deamidated gliadin antibodies (DGP) have shown
      promising results as serological markers for celiac disease. Serology has also
      been employed in monitoring the response to a gluten-free diet.Despite the gluten
      free diet being so effective, there is a growing demand for alternative treatment
      options. In the future, new forms of treatment may include the use of gluten
      degrading enzymes to be ingested with meals, the development of alternative,
      gluten-free grains by genetic modification, the use of substrates regulating
      intestinal permeability to prevent gluten entry across the epithelium, and,
      finally, the availability of different forms of immunotherapy.

PMID- 18803428
TI  - Diagnosis of malaria: challenges for clinicians in endemic and non-endemic
      regions.
AB  - Malaria is a leading cause of morbidity and mortality worldwide. Prompt diagnosis
      and treatment are critical factors in reducing morbidity and mortality, as
      delayed treatment of malaria increases the risk of death. Microscopy has long
      been the standard of malaria diagnosis, but newer diagnostic tests now offer
      advantages in certain settings. Malaria diagnosis is complicated by the fact that
      acquired immunity to malaria can result in asymptomatic infections. In a
      symptomatic (febrile) patient, no existing malaria diagnostic test can
      distinguish malarial illness from parasitemia with concomitant fever of another
      cause. In this review we discuss the available malaria diagnostic tests,
      appropriate applications for each, and the challenges of malaria diagnosis in
      both endemic and non-endemic settings.

PMID- 18803429
TI  - Biomarkers for Alzheimer disease in cerebrospinal fluid, urine, and blood.
AB  - Alzheimer disease is the most common cause of dementia, yet its clinical
      diagnosis remains uncertain until an eventual postmortem histopathology
      examination. Currently, therapy for patients with Alzheimer disease only treats
      the symptoms; however, it is anticipated that new disease-modifying drugs will
      soon become available.Diagnostic tools for detecting Alzheimer disease at an
      incipient stage that can reliably differentiate the disease from other forms of
      dementia are of key importance for optimal treatment. Biomarkers have the
      potential to aid in a correct diagnosis, and great progress has been made in the
      discovery and development of potentially useful biomarkers in recent years. This
      includes single protein biomarkers in the cerebrospinal fluid, as well as multi
      component biomarkers, and biomarkers based on gene expression. Novel biomarkers
      that use blood and urine, the more easily available clinical samples, are also
      being discovered and developed. The plethora of potential biomarkers currently
      being investigated may soon provide biomarkers that fulfill different functions,
      not only for diagnostic purposes but also for drug development and to follow
      disease progression.

PMID- 18803431
TI  - Assessing the value-adding impact of diagnostic-type tests on drug development
      and marketing.
AB  - OBJECTIVE AND METHODS: We explore the cash value of the companion diagnostics
      opportunity from the perspective of the pharmaceutical partner. Cashflow-based
      modeling is used to demonstrate the potential financial benefits of key
      relationships between the pharmaceutical and diagnostics industries. RESULTS: In
      four scenarios, the uplift in the net present value (NPV) of a proprietary
      medicine can exceed $US1.8 billion. By simple extrapolation, the uplifted NPV
      calculations allow realistic and plausible estimates of the companion diagnostic
      opportunity to be in the region of $US40 billion to $US90 billion. CONCLUSION: It
      is expected that such market valuation could drive a macroeconomic change that
      shifts healthcare practice from reactionary disease-treatment to proactive health
      maintenance.

PMID- 18803430
TI  - Pharmacogenetics of major depression: insights from level 1 of the Sequenced
      Treatment Alternatives to Relieve Depression (STAR*D) trial.
AB  - Major depression is a serious mental illness frequently associated with
      devastating consequences for those affected. Suicide rates are significantly
      elevated, creating a sense of urgency to identify effective yet safe treatment
      options. A plethora of antidepressants are available on the market today,
      designed to act on different neurotransmitter systems in the brain, providing the
      clinician with several treatment strategies. There is, however, very little
      guidance as to which antidepressant may be most successful in a certain
      individual. Biomarkers that can predict treatment outcome would thus be of great
      value, shortening the time until remission and reducing costs for the healthcare
      system by reducing unsuccessful treatment attempts. The proven contribution of
      heredity to major depression risk suggests that genetic markers may be good
      biomarkers for treatment outcome.The Sequenced Treatment Alternatives to Relieve
      Depression (STAR*D) study and a large ancillary pharmacogenetic study in 1953
      STAR*D participants constitute the largest effort to date to identify genetic
      predictors of antidepressant treatment outcome. In this review, the results of
      candidate gene studies carried out so far are summarized and discussed, and some
      future directions are proposed.

PMID- 18803433
TI  - Meeting the global demand of sports safety: the intersection of science and
      policy in sports safety.
AB  - Sports and physical activity are transforming, and being transformed by, the
      societies in which they are practised. From the perspectives of both competitive
      and non-competitive sports, the complexity of their integration into today's
      society has led to neither sports federations nor governments being able to
      manage the safety problem alone. In other words, these agencies, whilst promoting
      sport and physical activity, deliver policy and practices in an uncoordinated way
      that largely ignores the need for a concurrent overall policy for sports safety.
      This article reviews and analyses the possibility of developing an overall sports
      safety policy from a global viewpoint. Firstly, we describe the role of sports in
      today's societies and the context within which much sport is delivered. We then
      discuss global issues related to injury prevention and safety in sports, with
      practical relevance to this important sector, including an analysis of critical
      policy issues necessary for the future development of the area and significant
      safety gains for all. We argue that there is a need to establish the sports
      injury problem as a critical component of general global health policy agendas,
      and to introduce sports safety as a mandatory component of all sustainable sports
      organizations. We conclude that the establishment of an explicit intersection
      between science and policy making is necessary for the future development of
      sports and the necessary safety gains required for all participants around the
      world. The Safe Sports International safety promotion programme is outlined as an
      example of an international organization active within this arena.

PMID- 18803434
TI  - Physical activity and prevention of type 2 diabetes mellitus.
AB  - The worldwide prevalence of type 2 diabetes mellitus is increasing at a rapid
      rate, predominantly because of changes in environmental factors interacting with
      individual genetic susceptibility to the disease. Data from 20 longitudinal
      cohort studies present a consistent picture indicating that regular physical
      activity substantially reduces risk of type 2 diabetes. Adjustment for
      differences in body mass index between active and inactive groups attenuates the
      magnitude of risk reduction, but even after adjustment, a high level of physical
      activity is associated with a 20-30% reduction in diabetes risk. The data
      indicate that protection from diabetes can be conferred by a range of activities
      of moderate or vigorous intensity, and that regular light-intensity activity may
      also be sufficient, although the data for this are less consistent. The risk
      reduction associated with increased physical activity appears to be greatest in
      those at increased baseline risk of the disease, such as the obese, those with a
      positive family history and those with impaired glucose regulation. Data from six
      large-scale diabetes prevention intervention trials in adults with impaired
      glucose tolerance or at high risk of cardiovascular disease indicate that
      increasing moderate physical activity by approximately 150 minutes per week
      reduces risk of progression to diabetes, with this effect being greater if
      accompanied by weight loss. However, this level of activity did not prevent all
      diabetes, with 2-13% of participants per annum who underwent lifestyle
      intervention still developing the disease. Thus, while 150 minutes per week of
      moderate activity confers benefits, higher levels of activity may be necessary to
      maximize diabetes risk reduction in those at high baseline risk of the disease.
      In contrast, those at low baseline risk of type 2 diabetes, e.g. people with a
      very low body mass index and no family history of diabetes, will remain at low
      risk of developing diabetes whether they are active or not. Thus, the amount of
      physical activity required to confer low risk of diabetes differs according to an
      individual's level of baseline risk. Consequently, a 'one size fits all' mass
      population strategy may not provide the most appropriate approach when designing
      physical activity guidelines for the prevention of type 2 diabetes. Producing
      tailored guidelines with the specific aim of reducing risk of diabetes in high
      risk populations may provide an alternative approach.

PMID- 18803435
TI  - Oxygen consumption during functional electrical stimulation-assisted exercise in
      persons with spinal cord injury: implications for fitness and health.
AB  - A lesion in the spinal cord leads in most cases to a significant reduction in
      active muscle mass, whereby the paralysed muscles cannot contribute to oxygen
      consumption (VO2) during exercise. Consequently, persons with spinal cord injury
      (SCI) can only achieve high VO2 values by excessively stressing the upper body
      musculature, which might increase the risk of musculoskeletal overuse injury.
      Alternatively, the muscle mass involved may be increased by using functional
      electrical stimulation (FES). FES-assisted cycling, FES-cycling combined with arm
      cranking (FES-hybrid exercise) and FES-rowing have all been suggested as
      candidates for cardiovascular training in SCI. In this article, we review the
      levels of VO2 (peak [VO2peak] and sub-peak [VO2sub-peak]) that have been reported
      for SCI subjects using these FES exercise modalities. A systematic literature
      search in MEDLINE, EMBASE, AMED, CINAHL, SportDiscus and the authors' own files
      revealed 35 studies that reported on 499 observations of VO2 levels achieved
      during FES-exercise in SCI. The results show that VO2peak during FES-rowing (1.98
      L/min, n = 17; 24.1 mL/kg/min, n = 11) and FES-hybrid exercise (1.78 L/min, n =
      67; 26.5 mL/kg/min, n = 35) is considerably higher than during FES-cycling (1.05
      L/min, n = 264; 14.3 mL/kg/min, n = 171). VO2sub-peak values during FES-hybrid
      exercise were higher than during FES-cycling. FES-exercise training can produce
      large increases in VO2peak; the included studies report average increases of +11%
      after FES-rowing training, +12% after FES-hybrid exercise training and +28% after
      FES-cycling training. This review shows that VO2 during FES-rowing or FES-hybrid
      exercise is considerably higher than during FES-cycling. These observations are
      confirmed by a limited number of direct comparisons; larger studies to test the
      differences in effectiveness of the various types of FES-exercise as
      cardiovascular exercise are needed. The results to date suggest that FES-rowing
      and FES-hybrid are more suited for high-intensity, high-volume exercise training
      than FES-cycling. In able-bodied people, such exercise programmes have shown to
      result in superior health and fitness benefits. Future research should examine
      whether similar high-intensity and high-volume exercise programmes also give
      persons with SCI superior fitness and health benefits. This kind of research is
      very timely given the high incidence of physical inactivity-related health
      conditions in the aging SCI population.

PMID- 18803436
TI  - The role of motion analysis in elite soccer: contemporary performance measurement
      techniques and work rate data.
AB  - The optimal physical preparation of elite soccer (association football) players
      has become an indispensable part of the professional game, especially due to the
      increased physical demands of match-play. The monitoring of players' work rate
      profiles during competition is now feasible through computer-aided motion
      analysis. Traditional methods of motion analysis were extremely labour intensive
      and were largely restricted to university-based research projects. Recent
      technological developments have meant that sophisticated systems, capable of
      quickly recording and processing the data of all players' physical contributions
      throughout an entire match, are now being used in elite club environments. In
      recognition of the important role that motion analysis now plays as a tool for
      measuring the physical performance of soccer players, this review critically
      appraises various motion analysis methods currently employed in elite soccer and
      explores research conducted using these methods. This review therefore aims to
      increase the awareness of both practitioners and researchers of the various
      motion analysis systems available, and identify practical implications of the
      established body of knowledge, while highlighting areas that require further
      exploration.

PMID- 18803439
TI  - Warm-up and stretching in the prevention of muscular injury.

PMID- 18803437
TI  - A review of femoroacetabular impingement in athletes.
AB  - There are a multitude of well recognized hip and groin injuries that commonly
      affect athletes; however, a more recently recognized and possibly often
      overlooked cause of hip pain is that of femoroacetabular impingement (FAI). FAI
      is characterized by abutment of the femoral neck against the acetabular rim,
      which may occur by two mechanisms known as 'CAM' or 'pincer' impingement,
      although most commonly by a mixture of both. CAM impingement is characterized by
      abutment of the femoral neck against the acetabulum due to a morphological
      abnormality of the femoral head-neck junction. Pincer impingement occurs where an
      abnormality of the acetabulum results in impingement against an often normal
      femoral neck. Both CAM and pincer impingement are known to result in pathological
      consequences of cartilage delamination and labral lesions, leading to significant
      pain and disruption to athletic performance and activities of daily living in
      athletes. There are currently several methods of assessing the degree of
      impingement by use of CT and magnetic resonance imaging scans, which can be used
      in conjunction with magnetic resonance arthrography and arthroscopy to assess the
      damage caused to the underlying structures of the hip. Both open and arthroscopic
      surgical methods are used, with recent reports in athletes showing excellent
      results for lifestyle improvement and frequency of returning to sport. In cases
      of hip and groin pain in athletes, it is important to remember to look for
      typical history, and examination and imaging findings that may suggest a
      diagnosis of hip impingement. This article goes some way to explaining the
      principles, consequences and management of FAI.

PMID- 18803440
TI  - First isolation of Besnoitia besnoiti from a chronically infected cow in Spain.
AB  - Besnoitia besnoiti was isolated from a skin biopsy of a chronically infected cow
      from central Spain. Zoites released from macroscopic cysts were adapted to its
      culture in vitro on a MARC-145 cell monolayer. Tachyzoites produced in vitro were
      either cryopreserved or used for genomic DNA isolation. A 2206 nt sequence
      containing 18S ribosomal RNA gene, internal transcribed spacer 1 (ITS 1), and a
      partial sequence of 5.8S ribosomal RNA gene was amplified by PCR and sequenced.
      This sequence showed a 99-100% identity to 18S, ITS1, and 5.8S sequences of B.
      besnoiti published in databases. After analysis by transmission and scanning
      electron microscopy of isolated bradyzoites and tachyzoites, it was observed that
      their ultrastructural morphology coincided with B. besnoiti. The isolate
      characterized in this study was identified as B. besnoiti on the basis of the
      disease produced, molecular characteristics, and morphology. The B. besnoiti
      isolate was denoted as BbSpain-1; it is the first isolate obtained and
      characterized in Spain and one of the first European isolates adapted to grow in
      vitro. The isolation and in vitro production of this B. besnoiti isolate offers a
      good opportunity to study general aspects of bovine besnoitiosis, including
      epidemiology, pathogenesis, and diagnosis of this re-emergent disease.

PMID- 18803441
TI  - Toxicity of select organic acids to the slightly thermophilic acidophile
      Acidithiobacillus caldus.
AB  - Acidithiobacillus caldus is a thermophilic acidophile found in commercial
      biomining, acid mine drainage systems, and natural environments. Previous work
      has characterized A. caldus as a chemolithotrophic autotroph capable of utilizing
      reduced sulfur compounds under aerobic conditions. Organic acids are especially
      toxic to chemolithotrophs in low-pH environments, where they diffuse more readily
      into the cell and deprotonate within the cytoplasm. In the present study, the
      toxic effects of oxaloacetate, pyruvate, 2-ketoglutarate, acetate, malate,
      succinate, and fumarate on A. caldus strain BC13 were examined under batch
      conditions. All tested organic acids exhibited some inhibitory effect.
      Oxaloacetate was observed to inhibit growth completely at a concentration of 250
      microM, whereas other organic acids were completely inhibitory at concentrations
      of between 1,000 and 5,000 microM. In these experiments, the measured
      concentrations of organic acids decreased with time, indicating uptake or
      assimilation by the cells. Phospholipid fatty acid analyses indicated an effect
      of organic acids on the cellular envelope. Notable differences included an
      increase in cyclic fatty acids in the presence of organic acids, indicating
      possible instability of the cellular envelope. This was supported by field
      emission scanning-electron micrographs showing blebbing and sluffing in cells
      grown in the presence of organic acids.

PMID- 18803442
TI  - A 'RIPPER' Project: advancing rural inter-professional health education at the
      University of Tasmania.
AB  - INTRODUCTION: Attending to the shortage and sustainability of health care
      professionals and resources in rural areas in Australia is a continuing
      challenge. In response, there is a heightened focus on new models of healthcare
      delivery and collaboration that optimise the quality of patient care, respond to
      complex health needs and increase professional job satisfaction.
      Interprofessional rural health education within universities has been proposed as
      one way of addressing these challenges. BACKGROUND AND OBJECTIVE: This article
      reports on the development, design, implementation and evaluation of the RIPPER
      initiative (Rural Interprofessional Program Education Retreat). RIPPER is an
      interprofessional rural health education initiative developed by a team at the
      University of Tasmania's Faculty of Health Science. The objective of the program
      was to develop a rural interprofessional learning module for final year
      undergraduate health science students at the University of Tasmania. The program
      was first piloted in a rural Tasmanian community in 2006, with a second iteration
      in 2007. Participants in the program included approximately 60 students from the
      disciplines of Medicine, Nursing and Pharmacy. METHOD: The format and educational
      design of the RIPPER program was focussed on a multi-station learning circuit
      using interprofessional case-based scenarios. Each learning station employed
      experiential and interactive educational strategies that included high and low
      fidelity simulation, role play and reflection. The learning stations required
      students to work collaboratively in small interprofessional teams to respond to a
      series of rural emergency healthcare scenarios. RESULTS: Qualitative and
      quantitative evaluation data was collected from student participants over two
      years utilising a pre- and post-test quasi experimental design. Results
      demonstrated a positive shift in students' understanding of interprofessional
      practice and the roles and skills of other health professions. There was also an
      increase in the value ascribed by students to collaboration and team work as a
      way of problem solving and improving patient outcomes. CONCLUSION: The project
      evaluation indicated the importance of developing a sustainable and embedded
      interprofessional rural module within the undergraduate health science
      curriculum. The project evaluation findings also point to some of the strengths
      and limitations of implementing interprofessional education activities in a rural
      setting.

PMID- 18803443
TI  - Antimicrobial activity of acrylic intraocular lenses soaked in fourth generation
      fluoroquinolones.
AB  - PURPOSE: The aim of this study was to determine whether a commercially available
      brand of intraocular lenses (IOLs) soaked in moxifloxacin or gatifloxacin for 1
      or 60 min have antimicrobial properties. METHODS: The IOLs (N = 8-10/group) were
      soaked in saline, physiologic-strength moxifloxacin (1.8 microg/mL), or
      gatifloxacin (0.48 microg/mL) for 60 min or commercial-strength moxifloxacin (5
      mg/mL) or gatifloxacin (3 mg/mL) for 1 or 60 min. Presoaked IOLs and gatifloxacin
      antibiotic disks were plated on agar with quality-controlled ATCC 25923
      Staphylococcus aureus overlay. Bacterial kill zones were measured after 24 h.
      RESULTS: IOLs soaked in physiologic-strength gatifloxacin or saline for 60 min
      produced no measurable bacterial kill zone, and the mean bacterial kill zone for
      IOLs soaked in physiologic-strength moxifloxacin was significantly greater (P =
      0.011, 0 vs. 3.88 +/- 3.18 mm, respectively). Soaking the IOLs in commercial
      strength moxifloxacin or gatifloxacin for 1 or 60 min produced significantly
      larger bacterial kill zones (P < 0.0001, mean: > or =33 mm for all groups).
      Soaking for 1 min produced a significantly larger mean bacterial kill zone by
      moxifloxacinthan gatifloxacin-treated IOLs (P = 0.002, 38.80 +/- 3.74 mm, 34.30
      +/- 1.34 mm, respectively). The mean bacterial kill zone was significantly larger
      for IOLs soaked in commercial-strength moxifloxacin for 1 versus 60 min (P =
      0.002, 38.80 +/- 3.74 mm, 33.56 +/- 1.42 mm, respectively). There was no
      significant difference in the mean bacterial kill zone between IOLs soaked for 1
      or 60 min in commercial-strength gatifloxacin (34.30 +/- 1.34 mm, 33.67 +/- 0.50
      mm, respectively).

PMID- 18803444
TI  - Ocular pharmacokinetics of topically-applied ketoconazole solution containing
      hydroxypropyl beta-cyclodextrin to rabbits.
AB  - PURPOSE: The aim of this study was to develop an aqueous ketoconazole (KET) eye
      drop in order to increase the corneal permeability and improve ocular
      bioavailability following topical application. METHODS: Hydroxypropyl beta
      cyclodextrin (HP-beta-CD) was used to formulate an aqueous eye drop to improve
      the aqueous solubility of KET. A single dose of of either KET suspension (1.5%;
      KET-SP) or KET (1.5%)/HP-beta -CD (12.5%) solution (KET-CD) was applied to
      rabbits. Aqueous humor and cornea were collected after 5, 10, 20, 30, 45, 60, 90,
      120, and 180 min. KET concentrations were determined by high-performance liquid
      chromatography after extraction. RESULTS: After topically applying KET-CD, the
      KET concentrations in aqueous humor were significantly increased at 10
      approximately 120 min, compared with those of KET-SP (P < 0.05), whereas KET
      concentrations became undectable at 180 min after topically applying KET-SP. The
      highest levels of KET in aqueous humor (Cmax, 2.67 microg/mL) were obtained after
      a 20-min application of KET-CD, 6.1 times greater than that corresponding to the
      KET-SP at 30 min. The KET concentrations in aqueous humor for post-120- and 180
      min instillations of KET-CD were 57.9 and 34.5 times higher than that of KET-SP
      post-120 min, respectively. The KET-CD produced an over eightfold bioavailability
      (AUC(0-120), area under the concentration-time curve between 0 and 120 min)
      increase in aqueous humor over the KET-SP. Peak KET concentration in the cornea
      (118.24 microg/g) was achieved within 5 min after the instillation of KET-CD,
      18.4 times higher than that of KET-SP at the same time point, whereas the highest
      KET level in cornea was only 8.57 microg/g after a 10-min application of KET-SP.
      The KET levels in corneas obtained after the application of KET-CD were all much
      higher than those obtained by KETSP (P < 0.01). The KET-CD produced an over
      twelvefold bioavailability (AUC(0-120)) increase in corneas over the KET-SP.

PMID- 18803445
TI  - Treatment of migraine with prophylactic drugs.
AB  - BACKGROUND: Migraine is among the 10 most disabling disorders worldwide. Besides
      acute attack treatment, drug prophylaxis of migraine is important in order to
      improve the quality of life. OBJECTIVE: The aim of this paper is to describe the
      indications, principles and appropriate drugs with published evidence for the
      prophylaxis of migraine in general and in specific situations. METHODS: Based on
      the American and European guidelines for the treatment of migraine, the evidence
      for different drugs in the prophylaxis of migraine was evaluated. In addition,
      all trials on migraine drug prophylaxis published since the publication of the
      guidelines were included in the evaluation. These trials were identified by a
      literature search in MedLine, Embase and the Cochrane library. RESULTS: The drugs
      of first choice are beta-blockers, flunarizine, valproic acid and topiramate and,
      in the US, amitriptyline is also grouped among the first-choice drugs. Drugs of
      second choice, with less efficacy or poorer evidence, are venlafaxine,
      gabapentin, naproxen, butterbur root, vitamin B(2) and magnesium. The potential
      side effects are considered when choosing the appropriate prophylactic drug. All
      drugs used in migraine prophylaxis have been detected by chance and not by
      pathophysiological considerations. In the future, drugs developed on the basis of
      the current knowledge of migraine pathophysiology will hopefully be more
      effective.

PMID- 18803446
TI  - Pharmacological treatment in moderate-to-severe Alzheimer's disease.
AB  - BACKGROUND: Moderate-to-severe stage Alzheimer's disease (AD) is a clinically
      diagnosable entity that represents a substantial burden to our healthcare system
      in terms of its prevalence, symptomatology, caregiver stress and economics.
      OBJECTIVE: In this paper, we review the data from currently available clinical
      trials aimed at treatment of this later stage of the disease. METHODS: A
      literature search was performed and published randomized controlled trials (RCTs)
      in which the majority of the study population consisted of Alzheimer patients in
      the moderate-to-severe stage were selected for review. RESULTS: A total of nine
      RCTs were identified in which the study population consisted of mainly moderate
      to-severe AD patients. The results from these studies suggest that memantine and
      donepezil, individually or in combination, provide measurable global, cognitive
      and behavioral benefits in AD patients. CONCLUSION: Pharmacological treatment of
      moderate-to-severe AD patients can be beneficial. However, cost-benefit data are
      limited, and the long-term effects and the optimal duration of treatment as
      patients continue to progress to more severe stages are unknown and require
      further investigation.

PMID- 18803447
TI  - HER-2-positive metastatic breast cancer: trastuzumab and beyond.
AB  - BACKGROUND: The recognition achieved in the late 1980s of human epidermal growth
      factor receptor 2 as an appealing therapeutic target for breast cancer has led to
      the development of targeted therapies for patients with human epidermal growth
      factor receptor 2-overexpressing breast tumors. OBJECTIVES: The aim of the
      present review is to address the standard treatment of human epidermal growth
      factor receptor 2-positive metastatic breast cancer patients, which is currently
      based on the humanized monoclonal antibody trastuzumab and to describe the new
      treatment options available for patients progressing on trastuzumab-based
      therapies. METHODS: A broad literature research was performed in order to review
      treatments, starting from the developmental phase of trastuzumab to the most
      recent biologic agents being tested in human epidermal growth factor receptor 2
      positive disease. RESULTS: Trastuzumab combined with a taxane represents the
      first therapeutic option for human epidermal growth factor receptor 2-positive
      metastatic breast cancer. However, novel combinations of trastuzumab and
      chemotherapy still hold great interest for their remarkable activity and good
      tolerability. On the other hand, the dual epidermal growth factor receptor/human
      epidermal growth factor receptor 2 inhibitor lapatinib has been the first drug to
      be approved in combination with capecitabine for the treatment of patients who
      progress on trastuzumab-based therapies. Moreover, in the near future,
      trastuzumab plus another biologic agent targeting human epidermal growth factor
      receptor 2, either directly or indirectly, may represent an effective
      'chemotherapy-free' combination for trastuzumab-refractory patients.

PMID- 18803448
TI  - Paclitaxel and docetaxel in the treatment of breast cancer.
AB  - BACKGROUND: Paclitaxel and docetaxel are considered fundamental drugs in the
      treatment of breast cancer. OBJECTIVES: To review the current role of taxanes in
      the treatment breast cancer, with emphasis on data from randomized trials
      comparing the two taxanes. METHODS: We have reviewed the available evidence in
      the literature to gauge the results of therapy of early and advanced breast
      cancer with taxanes. RESULTS: Clinically benefits were first shown in metastatic
      setting. More recently, benefits have also been seen in the therapy of early
      stage disease. It seems reasonable to consider either drug as standard treatment
      for node-positive early stage or metastatic breast cancer. Future studies should
      explore the optimal way of combining taxanes with novel biological and cytotoxic
      drugs. CONCLUSION: Based on existing evidence, clinicians should choose a taxane
      based regimen for their patients, according to clinical activity, toxicity
      profile, pharmacokinetics, and a dosing schedule that best meets the therapeutic
      needs and convenience.

PMID- 18803449
TI  - Pharmacotherapy of neuroendocrine cancers.
AB  - BACKGROUND: Neuroendocrine tumors (NETs) of the diffuse neuroendocrine cell
      system often present a considerable diagnostic and therapeutic challenge.
      METHODS: We have reviewed the literature on NET treatment between 1979 and 2008
      (PubMed search: carcinoid or neuroendocrine tumor/tumour + treatment or
      management), and summarized current therapeutic options and recommendations.
      RESULTS: The majority of tumors are diagnosed at a stage that the only curative
      treatment, radical surgical intervention, is no longer an option. Biotherapy with
      somatostatin analogs is currently the most efficient treatment to achieve
      palliation. The interferon class of agents may have a role in selected
      individuals but substantial adverse events often limit their use. Conventional
      chemotherapy has minimal efficacy but may have some utility in undifferentiated
      or highly proliferating neuroendocrine carcinomas and pancreatic NETs. Hepatic
      metastases, depending on size, location and number, may be amenable to surgical
      resection, embolization or radio-frequency ablation. Peptide receptor targeted
      radiotherapy may lead to reduction in tumor size but in most circumstances has a
      tumor-stabilizing effect. A variety of antiangiogenesis and growth factor
      targeted agents have been evaluated but to date the results have failed to meet
      expectations. Thus, long-acting somatostatin analogs remain the only effective
      pharmacotherapeutic option that improves symptomatology and quality of life with
      minimal adverse effects.

PMID- 18803450
TI  - The therapeutic management of differentiated thyroid cancer.
AB  - BACKGROUND: The management of thyroid cancer is difficult because the tumors
      comprise a wide range of biologic behaviors, from small papillary thyroid
      microcarcinomas that pose little or no threat to survival for the patient, to
      anaplastic thyroid cancers that are arguably the most lethal tumor. Although it
      may be difficult initially to determine at which end of the prognostic spectrum a
      patient resides, one can ordinarily estimate a patient's risk for tumor
      recurrence and mortality based on a triad of features as simple as the patient's
      age at the time of diagnosis, the tumor stage at presentation, and its initial
      response to therapy. While staging systems are available to assist in the
      management process, all are inexact and leave wide gaps in the treatment plan for
      a given patient. This is largely because randomized controlled trials are lacking
      as a result of the low incidence and generally favorable prognosis of the
      disease. As a practical matter, it may sometimes be difficult to reassure a
      patient, given the generally favorable prognosis of this group of tumors, knowing
      that without adequate therapy some become unexpectedly aggressive and recur years
      after initial management. The treatment of these tumors rests on a fine balance
      of providing care that reflects the anticipated course of the disease without
      overtreating the patient or providing reassurance that is unfounded. OBJECTIVE:
      To outline the treatment strategy for patients with differentiated thyroid cancer
      based on the available literature and to guide clinicians through a management
      algorithm utilizing patient and tumor characteristics. METHODS: This review is
      limited to the treatment of patients with differentiated thyroid cancer -
      papillary and follicular thyroid cancer - and the standard therapy required for
      the majority of patients. RESULTS/CONCLUSION: The treatment of differentiated
      thyroid cancer requires a multidisciplinary approach, involving an experienced
      surgeon, radiologists and an endocrinologist. There are many unanswered questions
      in the management algorithm and ongoing research is needed to further define the
      best treatment strategy for patients with differentiated thyroid cancer.

PMID- 18803451
TI  - Interaction of current cancer treatments and the immune system: implications for
      breast cancer therapeutics.
AB  - Early diagnosis and treatment of breast cancer may account for the current
      improvement in the mortality of breast cancer. However, achieving a complete
      'cure' is the holy grail of cancer medicine and, in many cases, cancer patients
      still succumb to their ultimate fate. There is therefore a need to devise
      innovative therapies to overcome this problem. To this end, many emerging
      therapies utilizing the immune system to eradicate the residues of disease have
      been described in the preclinical and clinical arenas. However, there is very
      little work examining the impact of immunotherapy on the existing natural
      immunity. The relationship between antitumor immunity, in the form of
      immunotherapy (either passive or active), and current strategies of treatment
      also needs to be explored. If we are to improve the success of cancer treatment,
      we must understand how current therapies interact with the immune system and with
      the emerging immunotherapies. For breast-cancer treatment to be successful,
      therapeutics should be tailored towards antitumor immunity; they should also
      avoid tumor-specific tolerance. The sources of information used to prepare this
      paper were obtained through published work on Pubmed/Medline and materials
      published on the US/UK governmental agencies' websites.

PMID- 18803452
TI  - Dysmenorrhea in adolescents and young adults: from pathophysiology to
      pharmacological treatments and management strategies.
AB  - BACKGROUND: Dysmenorrhea is the most common gynecologic complaint among
      adolescent and young adult females. Dysmenorrhea is usually primary and is
      associated with normal ovulatory cycles and with no pelvic pathology. In
      approximately 10% of females with severe dysmenorrhea symptoms, pelvic
      abnormalities such as endometriosis or uterine anomalies may be found. OBJECTIVE:
      To review the current knowledge regarding the pathophysiology of dysmenorrhea, as
      well as review pharmacological treatments and strategies for management of
      dysmenorrhea in adolescent and young adult females. METHODS: Review of original
      articles on dysmenorrhea that have been published in the medical literature.
      RESULTS/CONCLUSIONS: Potent prostaglandins and potent leukotrienes play an
      important role in generating primary dysmenorrhea symptoms. Non-steroidal anti
      inflammatory drugs (NSAIDs) are the most common pharmacologic treatment for
      dysmenorrhea. A loading dose of NSAIDs (typically twice the regular dose) should
      be used as initial treatment for dysmenorrhea, followed by a regular dose until
      symptoms abate. Adolescents and young adults with symptoms that do not respond to
      treatment with NSAIDs for three menstrual periods should be offered hormonal
      treatment such as combined estrogen/progestin oral contraceptive pills (OCPs) for
      three menstrual cycles. If dysmenorrhea does not improve within 6 months of
      treatment with NSAID and OCPs, a laparoscopy is indicated to look for
      endometriosis. The goal of pharmacological treatment for endometriosis is to
      block its abnormal positive feedback loop. The abnormal loop consists of high
      local levels of estrogen in the lesions, which induce transcription of COX-2 and
      synthesis of prostaglandin E(2.) This results in further expression and activity
      of aromatase and a further increase in estrogen.

PMID- 18803453
TI  - Pharmacoeconomics of entecavir treatment for chronic hepatitis B.
AB  - BACKGROUND: Entecavir is a new antiviral agent for chronic hepatitis B virus
      (HBV) infection with potent HBV suppression and a low rate of viral resistance.
      OBJECTIVE: To review published studies on the pharmacoeconomics of entecavir for
      treatment of chronic HBV. METHODS: A literature search on Medline and Embase over
      the period of 1998 - 2008 was performed in April 2008 using keywords 'entecavir'
      and 'cost'. RESULTS/CONCLUSION: Four studies comparing the cost effectiveness of
      entecavir with lamivudine and/or adefovir for treatment with chronic HBV
      infection using either decision tree or Markov modeling were reviewed. All four
      studies showed that entecavir was cost-effective in the treatment of chronic HBV
      with the incremental cost per QALY (quality-adjusted life-year) gained below the
      commonly accepted benchmark. The results are mainly due to the lower complication
      rates and better quality of life of patients using entecavir which can offset the
      higher acquisition cost of the drug. Patient characteristics, comparing agents
      and model assumptions were different among the four studies and they should be
      taken into account when applying the results to real life situations.

PMID- 18803454
TI  - Cilostazol and peripheral arterial disease.
AB  - Peripheral arterial disease is both common and disabling. Contemporary management
      of peripheral arterial disease is multimodal, encompassing both medical and
      interventional treatments. Cilostazol (Pletal), a 2-oxoquinolone derivative, is
      currently licensed in the UK for the treatment of patients with intermittent
      claudication to improve their walking distance in the absence of tissue necrosis
      or rest pain. The therapeutic effects of cilostazol are thought to be mediated
      through antiplatelet, antiproliferative and vasodilatory activities. This review
      aims to provide an overview of the management of peripheral arterial disease
      focusing upon cilostazol pharmacotherapy.

PMID- 18803455
TI  - Mitiglinide: a rapid- and short-acting non-sulfonylurea insulinotropic agent for
      the treatment of type 2 diabetic patients.
AB  - This review article deals with mitiglinide, a rapid-acting non-sulfonylurea
      insulinotropic agent for the treatment of type 2 diabetic patients. Attention is
      drawn to the background history of mitiglinide, its chemistry, its determination
      in plasma, its metabolic pathway, preclinical investigations conducted - either
      in vitro on the uptake of mitiglinide by pancreatic islets, the effects of
      mitiglinide on ionic channels, its insulinotropic action and its effect on
      glucose metabolism in hepatocytes and its cardiovascular effects, or in vivo in
      animals - as well as to clinical investigations with mitiglinide.

PMID- 18803456
TI  - Azelaic acid 15% gel in the treatment of rosacea.
AB  - Rosacea represents a chronic inflammatory dermatosis of uncertain
      pathophysiology. There are several associated risk factors and the need for long
      term treatment is well recognized. This diverse disease is frequently difficult
      to manage and has a significant impact on quality of life. There are several
      topical and oral treatments available, of which azelaic acid 15% gel (Finacea) is
      the first new treatment for rosacea in more than a decade. Azelaic acid per se
      has multiple modes of action in rosacea, but an anti-inflammatory effect achieved
      by reducing reactive oxygen species appears to be the main pharmacological
      action. Clinical studies have shown that azelaic acid 15% gel is an effective and
      safe first-line topical therapeutic option in patients with mild-to-moderate
      papulopustular rosacea. Significant continuous improvement in the number of
      inflammatory lesions and in erythema has been shown over a period of 15 weeks.
      Adverse effects associated with azelaic acid 15% gel are mostly mild or transient
      and do not usually necessitate discontinuation of therapy.

PMID- 18803457
TI  - Fluticasone furoate nasal spray consistently and significantly improves both the
      nasal and ocular symptoms of seasonal allergic rhinitis: a review of the clinical
      data.
AB  - BACKGROUND: Allergic rhinitis (AR) is a highly prevalent disorder, which often
      manifests as both nasal (congestion, sneezing, itching and rhinorrhoea) and
      ocular (redness, watery eyes, itching and burning) symptoms. Until recently,
      efficacy against the ocular symptoms of AR has been inconsistent for any single
      intranasal corticosteroid (INS). Fluticasone furoate is an enhanced-affinity
      glucocorticoid with potent anti-inflammatory activity. OBJECTIVE: To assess
      better the efficacy of an INS in the treatment of both the nasal and ocular
      symptoms of seasonal AR (SAR). METHODS: Data from all four trials of fluticasone
      furoate nasal spray (FFNS) in the treatment of SAR are reviewed and critically
      considered. RESULTS: FFNS consistently and significantly improved the nasal and
      ocular symptoms of SAR in patients sensitised to several different seasonal
      allergens (grass, ragweed and mountain cedar pollen) in all trials. An integrated
      analysis of the results also confirmed improvements in both nasal and ocular
      symptom scores in previously under-represented adolescent patients treated with
      FFNS. CONCLUSION: FFNS is the first INS to show consistent nasal and ocular
      efficacy across all SAR trials.

PMID- 18803458
TI  - Could rusalatide acetate be the future drug of choice for diabetic foot ulcers
      and fracture repair?
AB  - Rusalatide acetate (Chrysalin) is an investigational drug being evaluated for
      treatment of chronic wounds and fractures. Rusalatide acetate interacts with cell
      surface receptors to stimulate a cascade of cellular and molecular wound healing
      events, including activation of nitric oxide signaling. Rusalatide acetate
      significantly accelerated healing of diabetic foot ulcers and distal radius
      fractures in Phase I/II clinical trials. Subsequently, in one of the largest
      Phase III fracture studies to date, rusalatide acetate showed significant
      acceleration of distal radius fracture healing radiographically but failed to
      meet its primary clinical endpoint - time to removal of immobilization - within
      the intent-to-treat population. Subset analysis showed that rusalatide acetate
      met this primary clinical endpoint and significantly accelerated radiographic
      healing in osteopenic women. Rusalatide acetate may therefore show its greatest
      efficacy in healing-impaired patients.

PMID- 18803459
TI  - Is rimonabant efficacious and safe in the treatment of obesity?
AB  - BACKGROUND: The incidence of obesity is increasing worldwide, and in the USA
      approximately 100 million adults are overweight or obese. Orlistat and
      sibutramine are the drugs used at present for weight loss, but they both have a
      relatively modest effect. OBJECTIVES/METHODS: This evaluation is of the
      Rimonabant in Obesity (RIO) programme of clinical trials, and of the first trial
      to determine whether rimonabant has any effect on a clinical outcome. The
      Strategy to Reduce Atherosclerosis Development Involving Administration of
      Rimonabant - the Intravascular Ultrasound Study (STRADIVARIUS) determined whether
      treatment with rimonabant decreased atherosclerosis. RESULTS: The individual
      trials of the RIO programme showed that rimonabant 20 mg caused body weight loss,
      and also caused small decreases in waist circumference, plasma triglycerides and
      fasting glucose levels, and the incidence of the metabolic syndrome, while
      increasing levels of HDL cholesterol. Gastrointestinal side effects were the most
      common reported in the individual trials. However, when the five trials were
      combined, a small but significant increase in the incidence of depression and
      anxiety became apparent with rimonabant 20 mg. STRADIVARIUS showed that
      rimonabant 20 mg had no effect on atherosclerosis that was not progressing in
      subjects who were mostly also taking antithrombotic agents, statins, beta
      blockers and angiotensin inhibitors. CONCLUSIONS: At present, it is doubtful
      whether the benefits of rimonabant outweigh the risks. Unless rimonabant is shown
      to have benefits in ongoing clinical outcome studies, there is little rationale
      to support its use in the treatment of obesity.

PMID- 18803460
TI  - Dynamic intracellular distribution of Eaf2 and its potential involvement in UV
      Induced DNA damage response.
AB  - Eaf2 encodes a tumor suppressor that plays multiple functions in transcriptional
      activation, apoptosis, and embryonic development. In this study, we utilized GFP
      EAF2 fusion protein to describe the dynamic subcellular movement of Eaf2. GFP
      EAF2 is preferentially localized to the nucleus, and in the presence of ELL, it
      accumulates in nuclear speckles. However, Eaf2 is an unstable nuclear protein
      whose stability is affected by serum. Further, we provided first evidence that
      nuclear distribution of Eaf2 is responsive to DNA damage. Following UV
      irradiation, Eaf2 is relocalized to the nucleolus, suggesting a possible
      functional involvement of Eaf2 in DNA damage response.

PMID- 18803461
TI  - Differential expression of lysyl oxidases LOXL1 and LOX during growth and aging
      suggests specific roles in elastin and collagen fiber remodeling in rat aorta.
AB  - The extracellular matrix (ECM) plays an important role in vascular tissue
      structure, maintenance, and function. Lysyl oxidases catalyze a key step in the
      posttranslational cross-linking of elastin and collagens in the ECM. Gene
      knockout studies in mice suggested a role for lysyl oxidase-like (LOXL1) in adult
      elastin synthesis and a role for its isoform, lysyl oxidase (LOX), in the
      synthesis of both collagens and elastin during development. However, the relative
      expression of both isoforms as a function of age is not known and was therefore
      investigated here. LOX and LOXL1 immunohistochemistry and real-time RT-PCR were
      performed during development, growth and aging in the aorta of LOU and Brown
      Norway (BN) rats, two inbred strains with different susceptibilities to arterial
      fragility. In addition, expression of genes encoding for elastic fiber proteins
      and type I collagen, together with elastin and collagen contents, was measured in
      adult and old rat aortas. High aortic LOX expression was observed early in the
      development (embryonic day 15), followed by a drastic reduction in adulthood,
      whereas LOXL1 was mainly detectable in the intima and media; its expression was
      maintained throughout life in the LOU rat. Expression of tropoelastin, type-I
      collagen, and LOXL1 genes was reduced in the aorta of 6-week-old BN rats. Aging
      is characterized by a decreased elastin/collagen ratio and a greatly decreased
      expression of LOX, tropoelastin, and type-I collagen. These findings indicate a
      different spatial and temporal expression of LOX and LOXL1 during growth and
      aging in the rat aorta and suggest specific roles for LOX and LOXL1 in the
      synthesis and remodeling of elastic and collagen fibers.

PMID- 18803462
TI  - Opioid and progesterone signaling is obligatory for early human embryogenesis.
AB  - The growth factors that drive the division and differentiation of stem cells
      during early human embryogenesis are unknown. The secretion of endorphins,
      progesterone (P(4)), human chorionic gonadotropin, 17beta-estradiol, and
      gonadotropin-releasing hormone by trophoblasts that lie adjacent to the
      embryoblast in the blastocyst suggests that these pregnancy-associated factors
      may directly signal the growth and development of the embryoblast. To test this
      hypothesis, we treated embryoblast-derived human embryonic stem cells (hESCs)
      with ICI 174,864, a delta-opioid receptor antagonist, and RU-486 (mifepristone),
      a P(4) receptor competitive antagonist. Both antagonists potently inhibited the
      differentiation of hESC into embryoid bodies, an in vitro structure akin to the
      blastocyst containing all three germ layers. Furthermore, these agents prevented
      the differentiation of hESC aggregates into columnar neuroectodermal cells and
      their organization into neural tube-like rosettes as determined morphologically.
      Immunoblot analyses confirmed the obligatory role of these hormones; both
      antagonists inhibited nestin expression, an early marker of neural precursor
      cells normally detected during rosette formation. Conversely, addition of P(4) to
      hESC aggregates induced nestin expression and the formation of neuroectodermal
      rosettes. These results demonstrate that trophoblast-associated hormones induce
      blastulation and neurulation during early human embryogenesis.

PMID- 18803463
TI  - A novel wire stent (Zebrastent) for ureteric stenting in stone patients.

PMID- 18803464
TI  - Novel way to 'cut' the risk of HIV transmission.

PMID- 18803465
TI  - AERO self-expanding hybrid stent for airway stenosis.
AB  - Self-expanding metal, as well as silicon, stents have long been available for use
      in the airway. Metal stents can be placed using a flexible bronchoscope and are
      less readily removed. Silicone stents require rigid bronchoscopy and general
      anesthesia for placement but are removable. Both technologies are prone to
      complications on a long-term basis. A new self-expanding hybrid stent, the AERO
      stent (Alveolus, Inc., NC, USA), combines the best features of metal and silicone
      stents with a completely covered nitinol framework. The potential advantages of a
      self-expanding hybrid stent include placement using flexible bronchoscopy under
      conscious sedation, easy removability and a potential reduction in common long
      term stent implant complications. This article profiles the AERO device and
      evaluates stent technology in general.

PMID- 18803466
TI  - Transcranial magnetic stimulation: a device intended for the psychiatrist's
      office, but what is its future clinical role?
AB  - Repetitive transcranial magnetic stimulation (TMS) is a novel, noninvasive,
      office-based device technology that delivers focused stimulation to the cortex of
      the brain by means of magnetic pulses. It is a promising therapeutic approach in
      a variety of neuropsychiatric disorders. A large number of clinical trials have
      examined repetitive TMS as a novel treatment for major depression, with
      additional significant work in schizophrenia, anxiety disorders and pain
      syndromes. In this review, we describe how repetitive TMS is administered
      clinically and discuss how excitatory and inhibitory forms of stimulation are
      applied depending on what is known of the underlying pathophysiology of the
      disorder. Future putative clinical applications of repetitive TMS in psychiatry
      are discussed, with the authors' perspective on its likely role in clinical
      practice. TMS is a promising form of neuromodulation therapy that will most
      likely become a significant part of clinical practice in the future.

PMID- 18803467
TI  - Results using the AO hook plate for dislocations of the acromioclavicular joint.
AB  - The AO Hook plate has been used for stabilization of acromioclavicular joint
      dislocations. We present our experience of this newly introduced device in a
      general hospital, since there are not many papers in the literature reporting on
      this. A total of 16 patients were treated with the AO Hook plate between November
      2001 and November 2003 at Princess Alexandra Hospital in Harlow, UK. For
      functional assessment 6 months after removal of the plate, the constant score and
      the pain visual analogue score were used. The pain visual analogue score ranged
      from 0 to 6 (mean: 0.87) and the constant score ranged from 78 to 100 (mean:
      96.4). In one instance, a patient developed instability after removal of the
      plate. The use of this device results in excellent functional outcome for the
      treatment of acromioclavicular joint dislocations.

PMID- 18803468
TI  - Blood pressure measuring devices: ubiquitous, essential but imprecise.
AB  - Blood pressure measurement is an essential, poorly performed skill, traditionally
      undertaken through auscultation and use of a mercury sphygmomanometer. However,
      its exclusivity to the clinical environment has changed substantially over the
      last 20 years with the introduction of automated blood pressure devices. This
      simplified self-measurement method has enabled increased patient involvement and
      surveillance, while also eliminating the observer error, measurement bias and
      white-coat effect associated with auscultatory measurement in the clinical
      setting. Rapid advances in technology have decreased the discrepancy between
      automated and auscultatory readings, evidenced by the increased number of devices
      to pass recognized validation standards. However, the limitation of automated
      device accuracy is still evident in certain patient groups, such as those with
      diabetes, an arrhythmia or preeclampsia. Therefore, careful consideration is
      warranted when selecting a noninvasive blood pressure measurement device to
      ensure optimum accuracy and reliability of readings.

PMID- 18803469
TI  - Key biological issues in contact lens development.
AB  - A contact lens is a medical device widely used as an alternative to spectacles in
      order to correct refractive vision problems. The evolution of polymeric
      biomaterials has heralded a continuous development in the materials used to
      produce contact lenses and maximize patient comfort and limit adverse events.
      Microbial keratitis (MK) is a relatively rare but potentially devastating
      condition associated with contact lens use, particularly with the extended wear
      of hydrogel lenses. It is the principal complication related to contact lens wear
      and the large population at risk make it a public health concern. Bacterial
      binding to the contact lens material is a precursor to the development of MK and
      is influenced by properties of the material and the bacteria. In order for
      bacteria to infiltrate the cornea there must be some degree of corneal damage,
      usually caused by trauma or hypoxia. The most recent materials available aim to
      allow the continuous wear of lenses while limiting corneal hypoxia, thus helping
      to prevent the development of MK. Limitations to the treatment of MK require that
      novel approaches may be necessary in order to limit bacterial adhesion to contact
      lens materials.

PMID- 18803470
TI  - Carotid angioplasty and stenting under protection: advantages and drawbacks.
AB  - Carotid stenosis is responsible for approximately 30% of strokes, and carotid
      endarterectomy is considered to be the gold-standard treatment. Carotid
      angioplasty and stenting (CAS) has been proposed as an alternative to surgery but
      the risk of neurological complications and brain embolism remains the major
      drawback to this procedure. Embolic protection devices (EPDs), which retain
      particles and debris generated during the procedure, have been proposed to reduce
      the frequency of neurological complications. Three types of EPD have been
      developed: distal occlusion balloon, distal filters and proximal protection
      devices. Preliminary clinical results indicate that the routine use of an EPD
      along with specifically designed flexible stents, increasing skills of the
      interventionist and appropriate drugs combine to reduce ischemic neurological
      complications and can achieve similar results to the best surgical series,
      particularly in high surgical risk patients. Recent prospective, multicenter
      controlled trials and registries evaluating CAS with EPD have demonstrated that
      the CAS results are, at least, not inferior to surgery for patients at high risk
      for surgery (Stenting and Angioplasty with Protection in Patients at High Risk
      for Endarterectomy study) and in symptomatic patients (Stent Supported
      Percutaneous Angioplasty of the Carotid Artery versus Endarterectomy study).
      However, all protection devices are not equivalent and have some drawbacks.
      Advantages and disadvantages of each EPD will be analyzed in this review,
      allowing a good choice of the EPD depending on the patient and the lesion.
      Nevertheless, there is now a consensus among specialists to perform all CAS with
      EPD. EPDs have become an integral part of CAS and the routine use of EPDs seems
      beneficial, leading to a 60% reduction of brain embolisms.

PMID- 18803471
TI  - Clinical tracheal replacement: transplantation, bioprostheses and artificial
      grafts.
AB  - The replacement of significant lengths of tracheal tissue still remains the
      unrivalled 'holy grail' of thoracic surgery. As a result of continuous
      developments and improvements in tracheal surgery throughout the last five
      decades, most tracheal lesions can now be resected and primary reconstruction
      effected safely. Today, very few patients present extensive tracheal lesions that
      necessitate tracheal replacement. The spectrum of tracheal substitutes ranges
      from autologous tissue flaps and patches to synthetic stents and prostheses to
      tissue-engineered scaffolding. In this review, the clinical achievements and
      conceivable developments of applying human allografts and biological and
      artificial prostheses will be discussed.

PMID- 18803472
TI  - Radiofrequency ablation for the treatment of lung neoplasm.
AB  - Lung cancer is the most common cause of cancer-related mortality in the USA.
      Surgical resection is the standard treatment for resectable disease; however, a
      significant percentage of patients with otherwise resectable lung cancer may have
      other comorbidities, precluding surgical resection. In patients with Stage I non
      small-cell lung cancer, conventional external-beam radiotherapy is typically
      offered as treatment in medically inoperable, high-risk patients with reported 5
      year survival rates of 10-30%. An emerging technology in the treatment of lung
      tumors is radiofrequency ablation, which is a thermal ablative technique and may
      be applicable in high-risk patients with lung cancer. In this article we will
      review the principles of radiofrequency ablation, the common devices in use, the
      experimental background, the results of 'ablate and resect' studies and the
      clinical experience with radiofrequency ablation in the treatment of lung
      neoplasm.

PMID- 18803473
TI  - Contraceptive devices: subcutaneous delivery systems.
AB  - Ever since natural sex hormones have been identified, their structure defined and
      their synthesis achieved, it became clear that their circulating half-life was
      too short to allow use in therapy. One of the modalities most thoroughly
      investigated to prolong their duration of action is to embed them in a polymeric
      matrix and administer them subcutaneously. Research and development activities of
      devices to be inserted under the skin have focused upon two modalities: the first
      utilizes the so-called nonbiodegradable devices, in which the matrix is fixed and
      the drug is made available through diffusion. In the second, biodegradable
      devices, the matrix dissolves during the process and both the active compound and
      the matrix components reach the circulation. Although a number of biodegradable
      systems have been investigated in the form of polymeric rod or micropellets, so
      far no system has reached the marketplace. Several matrices have been evaluated:
      poly(ortho esters), (polylactic-polyglycolic acid)co-polymers, poly-(epsilon
      caprolactone). In the case of nonbiodegradable systems, several have been in
      widespread use for years. The first such system, Norplant 1, consists of six
      capsules delivering levonorgestrel and lasts a minimum of 5 years; the second,
      called Norplant 2 (Jadelle), consists of only two rods delivering the same amount
      of steroid of the first system, for the same duration of time. A third system
      already on the market is made up of a single rod releasing etonogestrel, the
      active metabolite of desogestrel, with duration of action of 3 years. Additional
      systems are still at the premarket stage. Subcutaneous implants have several
      obvious advantages, first and foremost their duration of action that can extend
      to at least 5 years, making them especially suitable for family-planning programs
      in developing countries; in addition, they are user- independent, again a
      positive feature in certain settings. Among the disadvantages, is a relatively
      complex insertion procedure that, for older systems, required ad hoc trained
      personnel and a small incision, clearly a disincentive. Newer devices, however,
      require a much simpler insertion procedure. Extracting systems is also complex
      and if a woman is lost to follow-up, implants will remain in the subcutaneous
      tissue forever.

PMID- 18803474
TI  - Contraceptive devices: intravaginal and intrauterine delivery systems.
AB  - Substances with an antifertility activity can be delivered directly into the
      vagina and the uterus. Indeed, it has been known for decades that the vaginal
      mucosa is an excellent way through which to deliver a number of compounds to the
      general circulation. Research and development efforts have concentrated on rings
      delivering only progestins, or both an estrogen and a progestin. The only
      combined ring marketed so far releases 15 microg ethynyl estradiol and 120 microg
      etonogestrel, and has a failure rate between one and two per 100 women-years of
      use. It has a preset duration of action of 1 month, has to be inserted before day
      5 of the cycle, irrespective of the presence of menstrual flow, and withdrawn
      after 21 days, thereby allowing proper cycle control. Among rings releasing only
      a progestin, one device releasing progesterone has been marketed; all others are
      still under development. Unlike other long-term methods, vaginal rings do not
      require the involvement of a healthcare professional and can be inserted and
      removed by the user. The first attempt at achieving contraception by inserting a
      device in the uterus is 100 years old. Half a century later, medicated
      intrauterine systems were investigated; they are superior to inert devices and
      today a number of active principles, such as copper and progestogens, have been
      incorporated and tested when released from an intrauterine device (IUD). Copper
      releasing devices last more than 10 years, with cumulative pregnancy rates of
      between approximately 5 and 3, and cumulative expulsion rates between
      approximately 12 and 8. With all IUDs, bleeding and pain are the most common
      reasons for a request to withdraw a device. There is agreement that fertility
      after removal of a copper-IUD is not impaired. Finally, the overall risk of
      ectopic pregnancy is reduced in IUD users, compared with using no contraception.
      The first progestogen-releasing system contained progesterone, had 1-year
      duration of action and was marketed some 30 years ago; unfortunately, it was
      shown that failure caused an increase of extrauterine pregnancies. This
      potentially dangerous effect eventually led to the withdrawal of the device from
      the market. In the meantime, a device releasing the synthetic progestin
      levonorgestrel was being developed and has now been successfully marketed; it
      lasts for a minimum of 5 years and, although absorbed systemically, cyclic
      function is maintained. The system is one of the most effective methods of
      contraception available today: large clinical studies indicate a Pearl index of
      0.1 per 100 woman-years. Although a postfertilization effect cannot be excluded,
      in a majority of cases, intrauterine systems act as true contraceptives,
      preventing fertilization.

PMID- 18803476
TI  - Cancer screening: the clash of science and intuition.
AB  - The concept of early detection of cancer holds great promise and intuitive
      appeal. However, powerful biases can mislead clinicians when evaluating the
      efficacy of screening tests by clinical observation alone. Selection bias, lead
      time bias, length-biased sampling, and overdiagnosis are counterintuitive
      concepts with critical implications for early-detection efforts. This article
      explains these biases and other common confounders in cancer screening. The most
      direct and reliable way to avoid being led astray by intuitions is through the
      use of randomized controlled trials.

PMID- 18803477
TI  - Extensive amplification of human regulatory T cells alters their functional
      capacities and targets them to the periphery.
AB  - Repetitive antigen encounters together with a strong CD28 co-stimulatory signal
      were recently identified as driving extensive amplification of human regulatory T
      (Treg) cells; however, the consequences of this on the functional capacities of
      Treg cells remain unknown. In this report, we reveal that T cell receptor
      (TCR)/CD28-triggered amplification in vitro converts CD4+CD25(high)FoxP3+ Treg
      cells into a late memory phenotype associated with immunosenescence and loss of
      CD7. Accordingly, ex vivo-isolated CD7- Treg cells have shortened telomeres and
      decreased telomerase expression compared to the majority of "mature" CD7+ Treg
      cells. Although they resist spontaneous apoptosis, amplified CD7- Treg cells
      exhibit increased sensitivity to activation-induced cell death (AICD). Extensive
      amplification of Treg cells is, moreover, accompanied by an increased activation
      threshold, reduced suppressor capacities, and interleukin-10 (IL-10) secretion,
      but secretion of high amounts of IL-4. Concomitantly, amplified Treg cells
      express homing receptors targeting them to the periphery. This is confirmed in
      vivo by the extensive accumulation of CD7- Treg cells with shortened telomeres in
      chronic inflammatory skin lesions, including atopic dermatitis and lichen ruber.
      Our data indicate that extensive amplification upon repetitive TCR/CD28
      engagement alters the functional capacities of CD4+CD25(high) Treg cells toward
      less suppressive cells, but potential mediators in sustaining inflammatory
      reactions through IL-4.

PMID- 18803478
TI  - Age-dependent spatial memory loss can be partially restored by immune activation.
AB  - Aging is often associated with a decline in hippocampus-dependent spatial memory.
      Here, we show that functional cell-mediated immunity is required for the
      maintenance of hippocampus-dependent spatial memory. Sudden imposition of immune
      compromise in young mice caused spatial memory impairment, whereas immune
      reconstitution reversed memory deficit in immune-deficient mice. Analysis of
      hippocampal gene expression suggested that immune-dependent spatial memory
      performance was associated with the expression of insulin-like growth factor
      (Igf1) and of genes encoding proteins related to presynaptic activity (Syt10,
      Cplx2). We further showed that memory loss in aged mice could be attributed to
      age-related attenuation of the immune response and could be reversed by immune
      system activation. Homeostatic-driven proliferation of lymphocytes, which expands
      the existing T cell repertoire, restored spatial memory deficits in aged mice.
      Thus, our results identify a novel function of the immune system in the
      maintenance of spatial memory and suggest an original approach for arresting or
      reversing age-associated memory loss.

PMID- 18803479
TI  - Hydrodynamic parameters modulate biochemical, histological, and mechanical
      properties of engineered cartilage.
AB  - Functional engineered cartilage constructs represent a promising therapeutic
      approach for the replacement of damaged articular cartilage. The in vitro
      generation of cartilage tissue suitable for repair requires an understanding of
      the complex interrelationships between environmental cues, such as hydrodynamic
      forces, and tissue growth and development. In the present study, engineered
      cartilage constructs were cultivated in four well-defined hydrodynamic
      environments within a bioreactor, and correlations were established between
      construct ultrastructural and mechanical properties and key hydrodynamic
      parameters. Results suggest that even for similar composition, constructs may
      exhibit different mechanical properties due to differences in their
      ultrastructure that can be modulated by hydrodynamic parameters. For example,
      improved mechanical properties were observed in constructs that exhibited a thick
      fibrous outer capsule as a result of cultivation under increased hydrodynamic
      shear. In particular, uniformity in the contribution of the fluid velocity
      vectors (axial, radial, and tangential) to the total fluid velocity and shear
      stress were the hydrodynamic parameters that most affected the construct
      properties under investigation. The correlations identified here may be useful in
      the development of engineered tissue growth models that inform the design of
      bioreactor cultivation systems toward the production of clinically relevant
      engineered cartilage.

PMID- 18803480
TI  - In vitro and animal study of novel nano-hydroxyapatite/poly(epsilon-caprolactone)
      composite scaffolds fabricated by layer manufacturing process.
AB  - The purpose of this study was to propose a computer-controllable scaffold
      structure made by a layer manufacturing process (LMP) with addition of nano- or
      micro-sized particles and to investigate the effects of particle size in vitro.
      In addition, the superiority of this LMP method over the conventional scaffolds
      made by salt leaching and gas forming process was investigated through animal
      study. Using the LMP, we have created a new nano-sized
      hydroxyapatite/poly(epsilon-caprolactone) composite (n-HPC) scaffold and a micro
      sized hydroxyapatite/poly(epsilon-caprolactone) composite (m-HPC) scaffold for
      bone tissue engineering applications. The scaffold macropores were well
      interconnected, with a porosity of 73% and a pore size of 500 microm. The
      compressive modulus of the n-HPC and m-HPC scaffolds was 6.76 and 3.18 MPa,
      respectively. We compared the cellular responses to the two kinds of scaffolds.
      Both n-HPC and m-HPC exhibited good in vitro biocompatibility. Attachment and
      proliferation of mesenchymal stem cells were better on the n-HPC than on the m
      HPC scaffold. Moreover, significantly higher alkaline phosphatase activity and
      calcium content were observed on the n-HPC than on the m-HPC scaffold. In an
      animal study, the LMP scaffolds enhanced bone formation, owing to their well
      interconnected pores. Radiological and histological examinations confirmed that
      the new bony tissue had grown easily into the entire n-HPC scaffold fabricated by
      LMP. We suggest that the well-interconnected pores in the LMP scaffolds might
      encourage cell attachment, proliferation, and migration to stimulate cell
      functions, thus enhancing bone formation in the LMP scaffolds. This study shows
      that bioactive and biocompatible n-HPC composite scaffolds prepared using an LMP
      have potential applications in bone tissue engineering.

PMID- 18803481
TI  - Micropatterning of poly(ethylene glycol) diacrylate hydrogels with biomolecules
      to regulate and guide endothelial morphogenesis.
AB  - Angiogenesis, which is morphogenesis undertaken by endothelial cells (ECs) during
      new blood vessel formation, has been traditionally studied on natural
      extracellular matrix proteins. In this work, we aimed to regulate and guide
      angiogenesis on synthetic, bioactive poly(ethylene glycol)-diacrylate (PEGDA)
      hydrogels. PEGDA hydrogel is intrinsically cell nonadhesive and highly resistant
      to protein adsorption, allowing a high degree of control over presentation of
      ligands for cell adhesion and signaling. Since these materials are
      photopolymerizable, a variety of photolithographic technologies may be applied to
      spatially control presentation of bioactive ligands. To manipulate EC adhesion,
      migration, and tubulogenesis, the surface of PEGDA hydrogels was micropatterned
      with a cell adhesive ligand, Arg-Gly-Asp-Ser (RGDS), in desired concentrations
      and geometries. ECs cultured on these RGDS patterns reorganized their cell bodies
      into cord-like structures on 50-microm-wide stripes, but not on wider stripes,
      suggesting that EC morphogenesis can be regulated by geometrical cues. The cords
      formed by ECs were reminiscent of capillaries with cells participating in the
      self-assembly and reorganization into multicellular structures. Further,
      endothelial cord formation was stimulated on intermediate concentration of RGDS
      at 20 microg/cm(2), whereas it was inhibited at higher concentrations. This work
      has shown that angiogenic responses can be tightly regulated and guided by
      micropatterning of bioactive ligands and also demonstrated great potentials of
      micropatterned PEGDA hydrogels for various applications in tissue engineering,
      where vascularization prior to implantation is critical.

PMID- 18803482
TI  - Insulin-like growth factor-binding protein contributes to the proliferation of
      less proliferative cells in forming skin equivalents.
AB  - In this study, the effects and the mediating factors of dermal cells on the
      epidermal regenerative ability were investigated. Human epidermal cells were
      separated into rapidly adhering (RA) cells and slowly adhering (SA) cells and
      used for culturing skin equivalents (SEs). For dermal part, normal human
      fibroblasts, dermal sheath cells (DSCs), and dermal papilla cells were used. SEs
      produced using SA cells and DSCs showed a thicker epidermis and higher
      expressions of alpha(6)- and beta1-integrin than SEs using SA cells and normal
      fibroblasts showed. We hypothesized that DSCs may secrete specific cytokines that
      can influence the regenerative potential of epidermal cells, and compared
      cytokine secretion by DSCs and normal human fibroblasts. Using RayBio human
      cytokine antibody array C (series 1000), 120 cytokines were tested. Results
      showed that DSCs produced a much greater amount of insulin-like growth factor
      binding protein (IGFBP-2), angiogenin, and BMP-6 than normal human fibroblasts
      produced. On the basis of the cytokine antibody array, we next investigated
      whether IGFBP-2, angiogenin, or BMP-6 has effects on SEs reconstruction. The
      addition of IGFBP-2 induced a thicker and more mature epidermis and higher
      expressions of alpha(6)- and beta1-integrin, whereas BMP-6 exhibited little
      effect. Thus, the SEs with IGFBP-2 showed almost the same morphology of the SEs
      using DSCs. Further, p63, a putative keratinocyte stem cell marker, was more
      frequently observed in the basal layer of SE with IGFBP-2. In conclusion, IGFBP-2
      is a major factor from DSCs that affects epidermal regenerative capacity of skin
      and may play an important role for stemness maintenance in human epidermal
      keratinocytes.

PMID- 18803491
TI  - Treating survivors of torture and refugee trauma: a preliminary case series using
      qigong and t'ai chi.
AB  - OBJECTIVES: This paper seeks to explore the potential value of qigong and t'ai
      chi practice as a therapeutic intervention to aid in the treatment of survivors
      of torture and refugee trauma. DESIGN: The common effects of torture and refugee
      trauma are surveyed with a focus on post-traumatic stress disorder. An
      alternative theoretical framework for conceptualizing and healing trauma is
      presented. Evidence is reviewed from the scientific literature that describes how
      qigong and t'ai chi have been used in studies of the general population to
      alleviate symptoms that are also expressed in torture survivors. Observations are
      presented from a combined, simplified qigong and t'ai chi intervention with a
      convenience sample of four refugee survivors of torture. RESULTS: Preliminary
      observations from four cases and a review of the literature support the potential
      efficacy of incorporating qigong and t'ai chi into the treatment of survivors of
      torture and refugee trauma. CONCLUSIONS: The incorporation of qigong and t'ai chi
      into the treatment of torture survivors, within a new framework for healing
      trauma, merits further investigation.

PMID- 18803492
TI  - The effect of patient-selected music on early postoperative pain, anxiety, and
      hemodynamic profile in cesarean section surgery.
AB  - BACKGROUND: After cesarean section surgery, routine pharmacologic methods of
      analgesia--opioids and benzodiazepines--may impair the immediate close contact of
      mother and neonate for their sedative and emetic effects. OBJECTIVES: The aim of
      this study was to explore the effect of patient-selected music on postoperative
      pain, anxiety, opioid requirement, and hemodynamic profile. METHODS: A total of
      80 patients, American Society of Anesthesiologists (ASA) physical status I-II,
      scheduled to undergo general anesthesia and elective cesarean section surgery
      were enrolled. Patients were randomly allocated to receive 30 minutes of music or
      silence via headphones postoperatively. Pain and anxiety were measured with a
      visual analogue scale. Total postoperative morphine requirement as well as blood
      pressure and heart rate were recorded after the intervention period. RESULTS:
      Pain score and postoperative cumulative opioid consumption were significantly
      lower among patients in the music group (p < 0.05), while there were no group
      differences in terms of anxiety score, blood pressure, or heart rate (p > 0.05).
      CONCLUSIONS: Postoperative use of patient-selected music in cesarean section
      surgery would alleviate the pain and reduce the need for other analgesics, thus
      improving the recovery and early contact of mothers with their children.

PMID- 18803494
TI  - Society for Acupuncture Research: 2007 conference report: "The status and future
      of acupuncture research: 10 years post-NIH Consensus Conference".

PMID- 18803495
TI  - The status and future of acupuncture mechanism research.
AB  - On November 8-9, 2007, the Society for Acupuncture Research (SAR) hosted an
      international conference to mark the tenth anniversary of the landmark NIH
      [National Institutes of Health] Consensus Development Conference on Acupuncture.
      More than 300 acupuncture researchers, practitioners, students, funding agency
      personnel, and health policy analysts from 20 countries attended the SAR meeting
      held at the University of Maryland School of Medicine, Baltimore, MD. This paper
      summarizes important invited lectures in the area of basic and translational
      acupuncture research. Specific areas include the scientific assessment of
      acupuncture points and meridians, the neural mechanisms of cardiovascular
      regulation by acupuncture, mechanisms for electroacupuncture applied to
      persistent inflammation and pain, basic and translational research on acupuncture
      in gynecologic applications, the application of functional neuroimaging to
      acupuncture research with specific application to carpal-tunnel syndrome and
      fibromyalgia, and the association of the connective tissue system to acupuncture
      research. In summary, mechanistic models for acupuncture effects that have been
      investigated experimentally have focused on the effects of acupuncture needle
      stimulation on the nervous system, muscles, and connective tissue. These
      mechanistic models are not mutually exclusive. Iterative testing, expanding, and
      perhaps merging of such models will potentially lead to an incremental
      understanding of the effects of manual and electrical stimulation of acupuncture
      needles that is solidly rooted in physiology.

PMID- 18803497
TI  - Developments in acupuncture research: big-picture perspectives from the leading
      edge.
AB  - On November 8-9, 2007, the Society for Acupuncture Research (SAR) hosted an
      international conference to mark the tenth anniversary of the landmark NIH
      [National Institutes of Health] Consensus Development Conference on Acupuncture.
      More than 300 acupuncture researchers, practitioners, students, funding agency
      personnel, and health policy analysts from 20 countries attended the SAR meeting
      held at the University of Maryland School of Medicine, Baltimore, MD. This paper
      summarizes important invited lectures in the area of how the field has developed
      in the past decade, along with a focus on appropriate strategies for advancing
      the field. Specific topics include: the impact of the 1997 NIH Acupuncture
      Consensus Conference on acupuncture research; whole-system strategies for
      developing the evidence without distorting the medicine; use of qualitative
      research methods to explore acupuncture as a complex intervention; use of
      qualitative research approaches to explore some "missing" topics in acupuncture
      research; and the impact of acupuncture research on clinical practice. A
      concluding section focuses on future directions in acupuncture research.

PMID- 18803496
TI  - The status and future of acupuncture clinical research.
AB  - On November 8-9, 2007, the Society for Acupuncture Research (SAR) hosted an
      international conference to mark the tenth anniversary of the landmark National
      Institutes of Health Consensus Development Conference on Acupuncture. More than
      300 acupuncture researchers, practitioners, students, funding agency personnel,
      and health policy analysts from 20 countries attended the SAR meeting held at the
      University of Maryland School of Medicine, Baltimore, MD. This paper summarizes
      important invited lectures in the area of clinical research. Specifically,
      included are: a review of the recently conducted German trials and observational
      studies on low-back pain (LBP), gonarthrosis, migraine, and tension-type headache
      (the Acupuncture Research Trials and the German Acupuncture Trials, plus
      observational studies); a systematic review of acupuncture treatment for knee
      osteoarthritis (OA); and an overview of acupuncture trials in neurologic
      conditions, LBP, women's health, psychiatric disorders, and functional bowel
      disorders. A summary of the use of acupuncture in cancer care is also provided.
      Researchers involved in the German trials concluded that acupuncture is effective
      for treating chronic pain, but the correct selection of acupuncture points seems
      to play a limited role; no conclusions could be drawn about the placebo aspect of
      acupuncture, due to the design of the studies. Overall, when compared to sham,
      acupuncture did not show a benefit in treating knee OA or LBP, but acupuncture
      was better than a wait-list control and standard of care, respectively. In
      women's health, acupuncture has been found to be beneficial for patients with
      premenstrual syndrome, dysmenorrhea, several pregnancy-related conditions, and
      nausea in females who have cancers. Evidence on moxibustion for breech
      presentation, induction of labor, and reduction of menopausal symptoms is still
      inconclusive. In mental health, evidence for acupuncture's efficacy in treating
      neurologic and functional bowel disorder is still inconclusive. For chronic
      cancer-related problems such as pain, acupuncture may work well in stand-alone
      clinics; however, for acute or treatment-related symptoms, integration of
      acupuncture care into a busy and complex clinical environment is unlikely, unless
      compelling evidence of a considerable patient benefit can be established.

PMID- 18803500
TI  - Fabrication of precision scaffolds using liquid-frozen deposition manufacturing
      for cartilage tissue engineering.
AB  - The fused deposition manufacturing (FDM) system has been used to fabricate tissue
      engineered scaffolds with highly interconnecting and controllable pore structure,
      although the system is limited to a few materials. For this reason, the liquid
      frozen deposition manufacturing (LFDM) system based on an improvement of the FDM
      process was developed. Poly(D,L-lactide-co-glycolide) (PLGA) precision scaffolds
      were fabricated using LFDM from PLGA solutions of different concentrations. A
      greater concentration of PLGA solution resulted in greater mechanical strength
      but also resulted in less water content and smaller pore size on the surface of
      the scaffolds. LFDM scaffolds in general had mechanical strength closer to that
      of native articular cartilage than did FDM scaffolds. Neocartilage formation was
      observed in LFDM scaffolds seeded with porcine articular chondrocytes after 28
      days of culture. Chondrocytes in LFDM scaffolds made from low concentrations (15
      20%) of PLGA solution maintained a round shape, proliferated well, and secreted
      abundant extracellular matrix. In contrast, the FDM PLGA scaffolds had low cell
      numbers and poor matrix production because of heavy swelling. The LFDM system
      offered a useful way to fabricate scaffolds for cartilage tissue-engineering
      applications.

PMID- 18803499
TI  - Strategies and applications for incorporating physical and chemical signal
      gradients in tissue engineering.
AB  - From embryonic development to wound repair, concentration gradients of bioactive
      signaling molecules guide tissue formation and regeneration. Moreover, gradients
      in cellular and extracellular architecture as well as in mechanical properties
      are readily apparent in native tissues. Perhaps tissue engineers can take a cue
      from nature in attempting to regenerate tissues by incorporating gradients into
      engineering design strategies. Indeed, gradient-based approaches are an emerging
      trend in tissue engineering, standing in contrast to traditional approaches of
      homogeneous delivery of cells and/or growth factors using isotropic scaffolds.
      Gradients in tissue engineering lie at the intersection of three major paradigms
      in the field-biomimetic, interfacial, and functional tissue engineering-by
      combining physical (via biomaterial design) and chemical (with
      growth/differentiation factors and cell adhesion molecules) signal delivery to
      achieve a continuous transition in both structure and function. This review
      consolidates several key methodologies to generate gradients, some of which have
      never been employed in a tissue engineering application, and discusses strategies
      for incorporating these methods into tissue engineering and implant design. A key
      finding of this review was that two-dimensional physicochemical gradient
      substrates, which serve as excellent high-throughput screening tools for
      optimizing desired biomaterial properties, can be enhanced in the future by
      transitioning from two dimensions to three dimensions, which would enable studies
      of cell-protein-biomaterial interactions in a more native tissue-like
      environment. In addition, biomimetic tissue regeneration via combined delivery of
      graded physical and chemical signals appears to be a promising strategy for the
      regeneration of heterogeneous tissues and tissue interfaces. In the future, in
      vivo applications will shed more light on the performance of gradient-based
      mechanical integrity and signal delivery strategies compared to traditional
      tissue engineering approaches.

PMID- 18803501
TI  - Detection of Blastocrithidia spp. (Kinetoplastida: Trypanosomatidae) in Chagas
      disease vectors from Texas, USA.
AB  - Organisms highly similar to Blastocrithidia triatomae, a pathogenic parasite of
      Chagas disease triatomine bug vectors, were detected using polymerase chain
      reaction amplification and DNA sequence analysis of a segment of the small
      subunit rRNA gene in 3 of 203 triatomine specimens collected in Texas from June
      2005 to October 2006. The parasite was identified in three species of triatomine
      bugs (Triatoma gerstaeckeri, T. indictiva, and T. neotomae) collected from three
      distinct geographic locations. Flagellated organisms indistinguishable from
      Trypanosoma cruzi were observed by direct microscopy in hindgut material of two
      of the three specimens. Coinfection with T. cruzi and Blastocrithidia was
      detected by molecular methods in one of the specimens. Parsimony analysis
      provided strong support for clustering of the new sequences within a
      Blastocrithidia group, clearly separated from other flagellated protozoans.
      Confirmation of Blastocrithidia in U.S. triatomine species complicates
      microscopic diagnosis of T. cruzi due to the morphologic similarity of the
      parasites.

PMID- 18803502
TI  - The acquisition and internalization of Salmonella by the lesser mealworm,
      Alphitobius diaperinus (Coleoptera: Tenebrionidae).
AB  - In poultry broiler production facilities, it is important to understand the
      sources and contribution of reservoir populations of pathogens. The lesser
      mealworm beetle, Alphitobius diaperinus (Panzer), is a common pest in poultry
      litter that is reported to carry pathogens affecting both human and animal
      health. This study investigates whether the carriage of a bacterial pathogen
      occurs by the harboring of bacteria internally by these insects. Beetles were
      exposed to a marker bacterium, Salmonella enterica serovar Typhimurium-green
      fluorescent protein (ST-GFP), at concentrations up to 10(7) colony-forming units
      (cfu)/mL for 0.5 to 12 h, and then subsequently surface disinfected and
      dissected. The head, gastrointestinal tract and hemolymph were cultured for the
      presence of ST-GFP. This study definitively demonstrates the internal carriage of
      Salmonella by this insect and found that the beetles rapidly acquired bacteria
      from external sources and harbored the bacteria within their alimentary canal
      after exposure for 30 min at 10(4) cfu/mL and within the hemolymph after exposure
      for 2 h at 10(6) cfu/mL. Beetles internalized an average of 9.5 * 10(1) and 3.2 *
      10(3) after a 2-h exposure to 2 * 10(4) and 2 * 10(6) cfu/mL, respectively. The
      lesser mealworm is a serious pest within the poultry brooder and laying industry
      and because of their mobility, voracious feeding habits, and prey potential may
      represent an active source facilitating the dissemination of Salmonella.

PMID- 18803503
TI  - Rabies in China: an update.
AB  - Human rabies cases in China have continued to increase in recent years, reaching
      a new peak in 2007. Parallel with an increase in human rabies deaths, a number of
      animal species with rabies have been reported in the majority of rabies-endemic
      areas. In this report, the occurrence, status, and control of rabies in both
      humans and animals are reviewed. Vaccines and immunoglobulin for human and animal
      use and postexposure prophylaxis for human are also summarized. The current
      strategies for rabies elimination in China are presented.

PMID- 18803504
TI  - The use of monoclonal antibodies to Neisseria lactamica in an antigen selection
      to Neisseria meningitides B vaccine.
AB  - Abstract Neisseria lactamica, a commensal bacterium that is non-pathogenic to
      humans and is usually found in the upper respiratory tract of children, is
      closely related to the pathogenic species Neisseria meningitidis. Colonization by
      Neisseria lactamica can be responsible for the development of natural immunity to
      meningococcal infection in childhood, when rates of meningococcal carriers are
      low. These features suggest that N. lactamica components can be key elements in
      the production of a new vaccine for N. meningitidis. The production of monoclonal
      antibodies for N. lactamica is an important tool in the selection of new antigens
      for the preparation of a vaccine for N. meningitidis B.

PMID- 18803505
TI  - Production of monoclonal antibodies against the 8 kDa subunit of Echinococcus
      granulosus Antigen B (EgAgB8/2) using DNA immunization.
AB  - Cystic echinococcosis (CE), an endemic cosmopolitan zoonotic helminthic disease
      caused by the larval stage of Echinococcus granulosus, lacks reliable diagnostic
      tools that fulfill the criteria of high sensitivity and specificity. Antigen B
      (AgB), a thermostable lipoprotein that constitutes a considerable fraction of the
      cystic hydatid fluid (HF), is being considered as a suitable source for
      vaccination and immunodiagnosis of CE due to its high specificity. Genetic
      immunization was used to immunize BALB/c mice with the second subunit of antigen
      B (EgAgB8/2) for the production of monoclonal antibodies (MAb). Fusion products
      between the spleen cells and myeloma cells produced six MAbs of the following
      isotypes: IgG2a (two clones), IgG2b (three clones), and IgM (one clone). The MAbs
      were tested for their specificity to crude sheep hydatid fluid (CSHF) versus
      other antigens prepared from other helminthic parasites including Toxocara canis,
      Acanthocheilonema viteae, Fasciola hepatica, Schistosoma mansoni, and Taenia.
      Five MAbs reacted with E. granulosus antigens, one showed cross reactivity with
      S. mansonia antigens, and one showed a high reactivity with E. granulosus but was
      cross reactive with all helminthic antigens tested. Using SDS-PAGE and
      immunoblotting under reducing conditions, all MAbs identified the four AgB
      subunits with molecular weights of 8, 16, 24, and 36 kDa. Further work on the
      specificity and sensitivity of these MAbs as well as their use in detecting
      circulating parasite antigens and in antigen purification will be assessed in
      future studies.

PMID- 18803506
TI  - An immunomagnetic separation-PCR method for detection of pathogenic Leptospira in
      biological fluids.
AB  - Abstract Leptospirosis is a zoonotic disease that occurs worldwide and is caused
      by pathogenic bacteria of the genus Leptospira. Clinical manifestations of
      leptospirosis are similar to other febrile illnesses and this fact frequently
      retards the beginning of antibiotic therapy. Thus, early and accurate diagnosis
      is a prerequisite for proper treatment of leptospirosis. Antigen and DNA-based
      detection tests offer potential advantage over tests based on antibody detection
      for early diagnosis of leptospirosis since antibodies only reach detectable
      levels several days after the onset of the infection. This work describes a
      method for detection of pathogenic Leptospira that associates an immunoseparation
      step with a PCR assay and uses an internal amplification control (IAC) to ensure
      accuracy of the test. The immunoseparation was performed with protein A-magnetic
      beads in house coated with an MAb specific for LipL32, the major outer membrane
      protein of pathogenic Leptospira; PCR was performed using lipL32 specific
      primers. The IMS-PCR method enhanced detection of Leptospira in experimentally
      contaminated human sera and urine when compared to PCR performed alone. IMS-PCR
      was able to detect 10(2) Leptospira cells per mL of human sera and urine,
      corresponding to 25 genomic copies per PCR reaction.

PMID- 18803507
TI  - Generation and characterization of monoclonal antibodies to mTOR kinase.
AB  - Abstract Mammalian target of rapamycin (mTOR) is a serine/threonine kinase that
      plays a critical role in the regulation of basic cellular functions, including
      cellular growth and proliferation. In this study we describe the generation and
      characterization of novel monoclonal antibodies directed against mTOR protein
      kinase. A GST-tagged fragment of mTOR expressed in bacteria was used as an
      antigen. Antibody-producing hybridoma cells were obtained by fusing SP2/0 myeloma
      cells with splenocytes from immunized mice. Anti-mTOR antibody-producing
      hybridoma cell lines were first identified by enzyme-linked immunosorbent assay
      and then subcloned by limiting dilution. Antibodies produced by selected clones
      were further tested for their reactivity towards the GST/mTOR 1334-1504
      recombinant protein. Furthermore, antibody produced by F11 clone was shown to
      recognize specifically mTOR in different tissues and cell lines in Western
      blotting, immunoprecipitation, and immunohistochemistry. In addition, mTOR F11
      antibody was suitable for immunoprecipitating and testing mTOR activity in in
      vitro kinase assay. In summary, generated antibodies will be useful for
      investigating mTOR signaling complexes in normal and pathological states.

PMID- 18803508
TI  - A critical assessment of NOTES: a pessimistic view from an optimist.

PMID- 18803509
TI  - Laparoscopic total extraperitoneal inguinal hernia repair under spinal
      anesthesia: a study of 480 patients.
AB  - OBJECTIVES: Laparoscopic total extraperitoneal inguinal hernia repair (TEP) is
      conventionally performed under general anesthesia (GA), and regional anesthesia
      is usually preferred in patients where GA is contraindicated. In this paper, we
      present our experience of over 8 years of using spinal anesthesia (SA) as the
      first choice with the contention that it is a better alternative to GA. METHODS:
      SA was used in 480 patients over the last 8 years, and 464 patients underwent
      unilateral TEP. Strangulated and obstructed hernia patients were excluded, but
      irreducible hernia patients were included. Sedation was given if required, and
      the conversion to GA was done in patients not responding to sedation or with
      failure of SA. Comparative control included TEP performed under GA in our initial
      49 patients. RESULTS: Three (0.63%) patients required a conversion to GA.
      Hypotension requiring support was recorded in 75 (15.63%) patients.
      Postoperatively, 2.08% (10) patients had vomiting, as compared to 30.61% (15
      patients) in patients administered GA. In all, 35.83% (172) of patients required
      injectable diclofenac for their abdominal pain within 2 hours postoperatively,
      and oral analgesic was required in 301 (62.71%) patients within the first 24
      hours, while 89.80% (44) patients operated an under GA required injectable
      analgesics in the immediate postoperative period and subsequent oral analgesia
      request was the same as in patients with SA. Postural headache, persisting for an
      average of 2.6 days, was seen in 25 (5.21%) patients postoperatively. Average
      time to discharge was 2.3 days. Kernofsky's performance status showed a 98.6%
      satisfaction level in patients. CONCLUSIONS: TEP done under SA has a number of
      advantages over GA and should be used routinely.

PMID- 18803510
TI  - Reoperation of the biliary tract by laparoscopy: an analysis of 39 cases.
AB  - BACKGROUND: Previously, prior biliary tract surgery was considered a
      contraindication to laparoscopic biliary tract reoperation. In this paper, we
      present our experience with laparoscopic biliary tract reoperation for patients
      with the choledocholithiasis for whom the endoscopic sphincterotomy has failed or
      is contraindicated. PATIENTS AND METHODS: A retrospective analysis was performed
      on data from the attempted laparoscopic reoperation of 39 patients, examining
      open conversion rates, operative times, complications, and length of hospital
      stay. RESULTS: Of 39 cases, 38 were completed laparoscopically: 1 case required a
      conversion to the open operation because of difficulty in exposing the common
      bile duct. Mean operative time was 135 minutes. Mean postoperative hospital stay
      was 4 days. Procedures included 3 cases of laparoscopic residual gallbladder
      resection, 13 cases of laparoscopic common bile duct exploration and primary duct
      closure of choledochotomy, and 22 cases of laparoscopic common bile duct
      exploration and choledochotomy with T-tube drainage. There was 1 case of duodenal
      perforation during dissection, which was repaired laparoscopically. There were 2
      cases of retained stones. Postoperative asymptomatic hypermalasia occurred in 3
      cases. There were no complications due to port placement, no postoperative
      bleeding, bile or bowel leakage, and no mortality. At a mean follow-up time of 18
      months, there was no recurrence or formation of duct stricture. CONCLUSIONS: The
      laparoscopic biliary tract reoperation is safe and feasible for experienced
      laparoscopic surgeons and is an alternative choice for patients with
      choledocholithiasis for whom the endoscopic sphincterectomy has failed or is
      contraindicated.

PMID- 18803511
TI  - Duodenal perforations after endoscopic retrograde cholangiopancreatography:
      experience and management.
AB  - OBJECTIVE: The aim of this study was to summary the experiences and lessons from
      periduodenal perforations related to endoscopic retrograde
      cholangiopancreatography (ERCP) and endoscopic sphincterotomy (EST). METHODS: A
      retrospective review from 2004 to 2007 identified 9 patients (0.37%) of
      periduodenal perforation related to ERCP/EST. Charts were reviewed for the
      following parameters: clinical presentation of patients, ERCP findings,
      diagnostic methods, treatment (surgical or conservative procedures),
      complications, and outcome. RESULTS: Nine patients who had periampullary
      perforations received ERCP/EST for common bile duct stones. Cannulation was
      considered difficult in 7 of 9 patients, and the precut technique was used. The
      diagnosis was made due to subcutaneous emphysema or peritonitis, and 3 patients
      received emergent operations (e.g., external biliary or retroperitoneal
      drainage), and 1 patient had a reoperation for a retroperitoneal sealed abscess.
      Their median length of hospital stay was 50 days. The other 6 were treated
      conservatively with nasal-duodenal and nasal-biliary drainage. Their median
      length of hospital stay was 13 days. There was no mortality. CONCLUSIONS: The
      precut technical may be a risk factor of duodenal perforation. Early diagnosis of
      duodenal perforation is essential for an optimum outcome, and subcutaneous
      emphysema may be a sensitive sign. Although the management of perforation after
      ERCP/EST is still controversial, a selective management is proposed, based on the
      features of classification type. Nevertheless, duodenal and biliary drainage is
      essential in both surgical and conservative therapy.

PMID- 18803512
TI  - A framework for interactive visualization of digital medical images.
AB  - The visualization of medical images obtained from scanning techniques such as
      computed tomography and magnetic resonance imaging is a well-researched field.
      However, advanced tools and methods to manipulate these data for surgical
      planning and other tasks have not seen widespread use among medical
      professionals. Radiologists have begun using more advanced visualization packages
      on desktop computer systems, but most physicians continue to work with basic two
      dimensional grayscale images or not work directly with the data at all. In
      addition, new display technologies that are in use in other fields have yet to be
      fully applied in medicine. It is our estimation that usability is the key aspect
      in keeping this new technology from being more widely used by the medical
      community at large. Therefore, we have a software and hardware framework that not
      only make use of advanced visualization techniques, but also feature powerful,
      yet simple-to-use, interfaces. A virtual reality system was created to display
      volume-rendered medical models in three dimensions. It was designed to run in
      many configurations, from a large cluster of machines powering a multiwalled
      display down to a single desktop computer. An augmented reality system was also
      created for, literally, hands-on interaction when viewing models of medical data.
      Last, a desktop application was designed to provide a simple visualization tool,
      which can be run on nearly any computer at a user's disposal. This research is
      directed toward improving the capabilities of medical professionals in the tasks
      of preoperative planning, surgical training, diagnostic assistance, and patient
      education.

PMID- 18803513
TI  - Retroperitoneal endoscopic versus conventional open adrenalectomy: a cost
      effectiveness analysis.
AB  - BACKGROUND: A retrospective cost-effectiveness analysis was carried out,
      comparing retroperitoneal endoscopic and conventional adrenalectomy, which is
      based on a large group of patients, restricted in tumor size for the purpose of
      ensuring comparability. MATERIALS AND METHODS: Between 1990 and 2004, 61 patients
      underwent either an endoscopic or open adrenalectomy for tumors smaller than 6
      cm. A short-term, base cost-effectiveness analysis was performed to evaluate
      costs per day prevented, and a sensitivity analysis was calculated. RESULTS:
      Average recovery time, postoperative stay, and resumption to oral intake were
      significantly shorter in the endoscopic group, whereas operative time was longer.
      No major complications occurred in either group. In 3 endoscopic procedures
      conversion was indicated. The base cost-effectiveness ratio was 15.41 per day
      postoperative stay prevented by the endoscopic approach. The number needed to
      treat with endoscopic adrenalectomy to prevent 1 week of postoperative stay is 2.
      CONCLUSION: Retroperitoneal endoscopic adrenalectomy may be considered a cost
      effective procedure, compared to the conventional open adrenalectomy.

PMID- 18803514
TI  - Use of video capsule endoscopy in the setting of recurrent subacute small-bowel
      obstruction.
AB  - HYPOTHESIS: Video capsule endoscopy (VCE) can be used to diagnose subacute
      intestinal obstruction in patients with otherwise negative imaging studies.
      PATIENTS AND METHODS: Nine patients with symptoms consistent with intermittent
      small-bowel obstruction who received a VCE and ultimately required surgical
      intervention. RESULTS: Patients were identified who had symptoms consistent with
      subacute bowel obstruction and a negative diagnostic work-up prior to VCE. All 9
      patients underwent several radiologic and endoscopic examinations with no clear
      etiology for their symptoms. Ultimately, in every case, a stricture or mass was
      found to be the cause of the obstruction at either the time of VCE or exploratory
      laparotomy/laparoscopy. CONCLUSIONS: Patients can have a small-bowel stricture or
      mass that can cause symptoms of subacute small-bowel obstruction. Diagnosis of
      the lesion may be difficult in these patients and can often result in multiple
      nondiagnostic radiologic and endoscopic examinations. VCE can be helpful in
      finding these lesions, leading to surgical resection of the diseased bowel and a
      cure for the patient's signs and symptoms.

PMID- 18803515
TI  - Retroperitoneal, mediastinal, and subcutaneous emphysema, complicating
      colonoscopy and rectal polypectomy.
AB  - Complications of flexible endoscopy-though still rare-are increasing in frequency
      lately as more invasive procedures are routinely performed. Perforation,
      hemorrhage, coagulation disorders, thrombophlebitis, and splenic rupture have all
      been reported to complicate colonoscopy and colorectal polypectomies. In this
      paper, we report on a case of retroperitoneal, mediastinal, and neck surgical
      emphysema, complicating colonoscopy and rectal polypectomy, presented initially
      as a change in the voice and facial swelling.

PMID- 18803516
TI  - Successful minimally invasive repair of spontaneous esophageal perforation.
AB  - Esophageal perforations with a mediastinal abscess are medical emergencies with a
      significant mortality rate. Prompt management is mandatory, and a variety of
      treatment strategies have been advocated. In the case of a spontaneous rupture of
      the esophagus (the so-called Boerhaave's syndrome), the treatment of choice
      involves the surgical repair of the esophageal defect, usually accomplished
      through a laparotomy or thoracotomy. In this paper, we present a case of an
      elderly patient with severe comorbidities, in which a minimally invasive approach
      was attempted and a complete repair was successfully accomplished.

PMID- 18803518
TI  - Robotically assisted total laparoscopic radical trachelectomy for fertility
      sparing in stage IB1 adenosarcoma of the cervix.
AB  - Adenosarcomas are rare cervical tumors with unknown optimal treatment, which
      often affects young women. A 23-year-old woman was found to have a stage IB1
      adenosarcoma of the cervix. She underwent a robotically assisted total
      laparoscopic radical trachelectomy with the placement of abdominal cerclage for
      the sparing of fertility.

PMID- 18803517
TI  - Laparoscopic resection of an intraductal papillary mucinous carcinoma in ectopic
      pancreatic tissue.
AB  - Intraductal papillary mucinous neoplasia (IPMN) is a comparatively recently
      recognized pancreatic neoplasm with considerable malignant potential. Surgical
      removal is the only therapy known to provide a cure, but the extent of surgery
      required is still a matter of discussion. Ectopic pancreatic tissue can occur in
      a variety of other locations within the gastrointestinal tract and is also known
      to harbor pathologic conditions that affect normally located pancreatic tissue.
      In this paper, we present a case of an intraductal papillary mucinous carcinoma
      arising within the ectopic pancreatic tissue in the wall of the proximal
      duodenum. The lesion was removed by a laparoscopic resection. We believe this to
      be the first described case of a malignant IPMN to arise within ectopic
      pancreatic tissue and also the first report of the laparoscopic removal of any
      ectopic pancreatic IPMN.

PMID- 18803519
TI  - Videothoracoscopic treatment of a rare complication of nasojejunal tube
      insertion.
AB  - OBJECTIVE: Intubation of the tracheobronchial tree is the most common type of
      malposition during the placement of narrow-bore enternal tubes. CASE REPORT: In
      addition to other treatment components in a 65-year-old female, nasojejunal
      feeding was started to treat her for severe acute pancreatitis. After the
      placement of the narrow-bore feeding tube, she developed dyspnea and huskiness.
      On auscultation and X-ray investigation, the right pneumothorax was detected and
      the tube was found in the chest cavity. The diagnosis was confirmed by
      bronchoscopy. Videothoracoscopic resection and closure of the lacerated lung,
      using a tube thoracostomy, were performed. The patient recovered after
      postoperative conservative treatment for her pancreatitis. CONCLUSION:
      Pneumothorax and laceration of the lung-caused by the malposition of narrow-bore
      enternal tube-can be successfully treated by applying videothoracoscopy.

PMID- 18803520
TI  - Pilot study of transesophageal endoscopic surgery: NOTES esophagomyotomy,
      vagotomy, lymphadenectomy.
AB  - OBJECTIVES: The aim of this study was to evaluate the technical feasibility of
      endosonographically-assisted transesophageal access for vagotomy,
      esophagomyotomy, and lymphadenectomy in a nonsurvival study with six porcine
      models in an animal laboratory with general anesthesia. METHODS:
      Saline/hydroxypropylmethylcellulose (HPMC) was injected into the submucosa with a
      subsequent biliary balloon dissection, creating a substantial submucosal space
      for a cap-fitted endoscope. A distal esophageal myotomy was performed after
      access into the thoracic cavity. Over the course of 6 pigs, esophagomyotomy
      (simulating a Heller myotomy), vagotomy, and lymphadenectomy were performed. The
      esophageal insertion/access site was sealed by the flap of mucosa. RESULTS: Using
      a midesophageal entrance point, successful thoracic access and therapeutic
      interventions involving the esophagus and periesophageal structures were
      performed in 6 pigs. CONCLUSIONS: The submucosal saline/HPMC tunneling technique
      allowed for successful access to the upper mediastinum through the esophagus with
      feasible therapeutic interventions.

PMID- 18803521
TI  - Thoracoscopic versus open repair of tracheoesophageal fistula and esophageal
      atresia.
AB  - BACKGROUND/OBJECTIVE: Recent studies show the minimally invasive approach to the
      repair of esophageal atresia (EA) and tracheoesophageal fistula (TEF) is
      feasible. This study aimed to evaluate the efficacy and safety of the
      thoracoscopic versus open techniques. METHODS: We performed a retrospective
      review of EA/TEF cases from June 2000 to July 2006. Patient characteristics,
      operative time, blood loss, duration of narcotic usage, time to extubation, time
      to first oral feeding, length of stay, complications, and follow-up were
      analyzed. RESULTS: Thirty-five type-C EA/TEF patients were evaluated. Two
      patients with excessively long gaps who required esophageal "bougienage"
      stretching were excluded. Twenty-five patients underwent traditional repair
      through thoracotomy. There were 8 thoracoscopic attempts, 7 of which were
      successfully completed without a conversion. The mean operative time was 130
      minutes (range, 75-240) for the thoracoscopic approach, compared to 123 (range,
      82-205) for the thoracotomy; mean duration of narcotic use was 5 days (range, 1
      12), as compared to 23 (range, 2-190); the mean time to extubation was 4.6 days
      (range, 1-12), compared to 19 (range, 3-150); the mean days to per os feeding
      were 9.8 days (range, 7-17) versus 37 (range, 7-360); and the mean length of stay
      was 21.8 days (range, 11-38), compared to 66 (range, 8-280). There were no
      intraoperative complications or deaths in either group. The anastomotic leak rate
      was 14 versus 20%, whereas the stricture rate was 14 versus 50% for the closed
      and open techniques, respectively. Of the thoracoscopic group, 87.5% had at least
      one major associated anomaly, compared with 70% of patients undergoing
      thoracotomy. Follow-up for the thoracoscopic and open groups were 18 and 28
      months, respectively. CONCLUSION: Our results suggest that the outcomes of the
      thoracoscopic technique are comparable to that of the open technique. However,
      the number is small, and more data are needed to further evaluate the procedure.

PMID- 18803522
TI  - Laparoscopy in management of abdominal pain in children.
AB  - The aim of our study was to evaluate the role of diagnostic and therapeutic
      laparoscopy for abdominal pain in children. Fifty-four children under the age of
      12 years who presented with an acute abdomen with symptoms of duration of less
      than 72 hours (N = 21), and recurrent abdominal pain (RAP) with duration of
      symptoms ranging from 2 to 18 months (N = 33) were included in this study.
      Patients who presented with hemodynamic instability and signs of generalized
      peritonitis were excluded from this study. All patients were evaluated
      thoroughly, including a detailed history with relevant investigations and other
      specific tests, such as the Mantoux test, urinary porphobilinogen, video
      electroencephalograph, M. tuberculosis polymerase chain reaction, and so on, were
      taken to rule out rare causes of RAP. The results of the study were assessed, and
      it is concluded that diagnostic laparoscopy allows for establishing a prompt,
      accurate diagnosis in the acute abdomen without a therapeutic delay and
      unnecessary hospital observation. Laparoscopy early in the course of debilitating
      chronic abdominal pain in children provides economic benefit by eliminating many
      low-yield imaging studies and also minimizes lost time from school.

PMID- 18803523
TI  - Minilaparoscopic nerve-sparing extravesical ureteral reimplantation for primary
      vesicoureteral reflux: a preliminary report.
AB  - BACKGROUND: To validate its safety and efficacy, we evaluated our preliminary
      results of the three-port minilaparoscopic nerve-sparing extravesical ureteral
      reimplantation for patients with vesicoureteral reflux (VUR). METHODS: Between
      July 2005 and February 2007, 9 consecutive patients (4 girls and 5 boys) with a
      mean age of 3.4 years (range, 7 months to 5 years) underwent a minilaparoscopic
      nerve sparing extravesical ureteral reimplantation for VUR. A 30-degree 3-mm
      telescope and two 3-mm trocars were used for the reimplantation. Minimal handling
      and dissection of the ureter and ureterovescial junction was adhered to spare the
      nerves. RESULTS: A total of 14 ureters were reimplanted (4 unilateral and 5
      bilateral). Mean follow-up period was 8.7 months. The mean operative time was 170
      minutes in unilateral reimplantations and 218 minutes in the bilateral one. There
      was no intraoperative complication. All patients resumed oral intake in the first
      postoperative morning. The Foley catheters were removed within 24-36 hours after
      surgery. None of them had urinary retention after catheter removal. Voiding
      cystourethrography was done 3-4 months after surgery. A complete resolution of
      reflux was identified in 11 of 14 units, a downgrading of reflux in 2 of 14
      units, and ureterovesical junction stenosis in 1 of 14. Open reimplantation was
      done for the ureter with postoperative ureterovesical junction stenosis.
      CONCLUSIONS: The three-port minilaparoscopic nerve-sparing extravesical ureteral
      reimplantation was a safe, effective techinique for the treatment of VUR.

PMID- 18803524
TI  - Laparoscopic intragastric stapled cystgastrostomy of pancreatic pseudocyst in a
      child.
AB  - The current management for pancreatic pseudocysts in children is predicated on
      adult techniques and includes open, endoscopic, percutaneous, and laparoscopic
      drainage. In this paper, we report our technique using two intragastric cannulas
      for the creation of a laparoscopic stapled pancreatic cystgastrostomy.

PMID- 18803525
TI  - O-phospho-L-serine: a modulator of bone healing in calcium-phosphate cements.
AB  - Bone substitution materials are seen as an alternative to autogenous bone
      transplants in the reconstruction of human bone structures. The aim of the
      present animal study was to evaluate the clinical handling and the conditions of
      bone healing after the application of a phosphoserine and collagen-I-modified
      calcium-phosphate cement (Biozement D). The application of phosphoserine is
      supposed to influence the texture of the extracellular matrix. Standardised bone
      defects were created in the lower jaw of 10 adult minipigs. These defects were
      reconstructed with a pasty calcium-phosphate cement mixture. After a healing time
      of 4 months, the animals were sacrificed. The mandibles of all animals were
      resected and non-decalcified histological sections of the areas of interest were
      prepared. The experiment was evaluated by means of qualitative histology and
      histomorphometry. The hydroxyapatite cement entirely hardened intraoperatively.
      Modelling and handling of the cement was facile and the margin fit to the host
      bone was excellent. Histology showed that resorption started in the periphery and
      proceeded exceptionally fast. The bony substitution, especially in phosphoserine
      endowed cements, was very promising. After a healing period of 4 months,
      phosphoserine cements showed a bone regeneration of nearly two-thirds of the
      defect sizes. In the applied animal experiment, the newly developed
      hydroxyapatite collagen-I cement is well suited for bone substitution due to its
      easy handling, its excellent integration and good resorption characteristics. The
      addition of phosphoserine is very promising in terms of influencing resorption
      features and bone regeneration.

PMID- 18803526
TI  - The influence of the root cross-section on the stress distribution in teeth
      restored with a positive-locking post and core design: a finite element study.
AB  - Human teeth with substantial coronal defects are subject to reconstruction by
      means of post and core restorations. Typically, such a restoration comprises a
      slightly cylindrical post onto which an abutment of varying shape, depending on
      the designated restoration, is attached. As clinical results are not satisfactory
      to date, we proposed a new proprietary post and core design which makes use of
      positive locking. As this prefabricated system is not customised to an individual
      root's cross-sectional geometry (usually oval), a varying amount of radicular
      dentin is left in periphery of the core's outer edge. The aim of this study was
      to assess the implications of this fact, i.e., whether the root has to endure
      higher overall stress levels which ultimately may lead to failure of one of the
      components involved. A series of finite element simulations were performed to
      evaluate stress and strain on the system, in which the proposed post and core was
      embedded into a virtual dentin cylinder of different diameters, ranging from
      flush mounting of the restoration to a dentin excess of 4 mm, and subsequently
      loaded with forces with two angles of attack (90 degrees and 130 degrees ). The
      results show that flush mounting yields an agreeable stress and strain
      distribution within the radicular dentin, but overall stress levels drop
      significantly with an excess of 0.5 mm of surrounding dentin. More than 1 mm
      excess was not found to have profound positive effects.

PMID- 18803527
TI  - Finite element representation of bone substitute remodelling in the jaw bone.
AB  - The finite element (FE) method was originally developed on a physical basis for
      the computation of structure-mechanical problems. Meanwhile, it has been widely
      applied to medical issues. This study sought a suitable method to build a FE
      model for remodelling processes in osseous defects supplemented with bone
      substitute material. For this purpose, the second right premolars were extracted
      from four pig mandibles (Sus scrofa domesticus) and the extraction alveoli were
      provided with synthetic bone substitute material. After 70 days, a segmented
      osteotomy of this area was performed for specimen collection. Radiographs of the
      specimens were taken in defined planes before and after fixation and embedded
      with Technovit 9100. Fixation-related shrinkage was quantified from the
      radiographs using reference lines. Computer tomographic (CT) and microCT images
      of the fixed and embedded specimens were obtained. From these data, a FE model
      was built. The construction of a FE model is sufficient to represent bone
      remodelling after supply of bone substitute material. The use of microCT data
      permits building a clearly more precise model.

PMID- 18803528
TI  - The biomaterial influences the ossification after sinus floor elevation using
      tissue-engineered bone grafts.
AB  - Sinus floor elevation is the standard procedure that allows dental implant
      insertion in the atrophic posterior maxilla. Instead of autogenous bone, tissue
      engineered bone grafts can be used, but clear comparative clinical studies also
      assessing the influence of the biomaterial are missing. In six patients, tissue
      engineered bone grafts were used in eight sinus floor elevations. After culturing
      osteoblast-like cells from biopsies of the maxilla, they were seeded on scaffolds
      made either from demineralised bovine bone matrix (DBBM) or from solvent
      dehydrated mineralised bone (SDBB), and grafted. In all patients primary wound
      healing was without complications, except for one patient in the SDBB group.
      After 12 months, implant insertion was possible only in the SDBB group; in the
      DBBM group, fibrous connective tissue was found in an attempt of implant
      insertion. After 5 months, implant placement was performed in one patient of each
      group. However, the two implants inserted in the DBBM group were lost after 6
      weeks. Histology of the bone cores in the DBBM group at 5 months showed lamellar
      bone and osteoid, and at 12 months showed fibrous connective tissue. Inflammation
      and some resorption of the scaffold was found 5 months after SDBB grafting, and
      after 12 months cancellous bone formation encapsulating SDBB remnants were
      observed. These preliminary data suggest that the preparation method of the
      bovine bone matrix, in particular the mineral content, and therefore the
      mechanical stability may have some influence on the generation of new bone.

PMID- 18803529
TI  - Population genetic screening for hereditary haemochromatosis: are we a step
      closer?

PMID- 18803530
TI  - Antibiotic prophylaxis against infective endocarditis: time to rethink.

PMID- 18803531
TI  - After ENHANCE: the cholesterol hypothesis is alive and well.

PMID- 18803532
TI  - A 5- versus 3-day course of oral corticosteroids for children with asthma
      exacerbations who are not hospitalised: a randomised controlled trial.
AB  - OBJECTIVE: To determine whether a 5-day course of oral prednisolone is superior
      to a 3-day course in reducing the 2-week morbidity of children with asthma
      exacerbations who are not hospitalised. DESIGN, SETTING AND PARTICIPANTS: Double
      blind randomised controlled trial of asthma outcomes following a 5-day course of
      oral prednisolone (1 mg/kg) compared with a 3-day course of prednisolone plus
      placebo for 2 days. Participants were children aged 2-15 years who presented to
      the emergency departments of three Queensland hospitals between March 2004 and
      February 2007 with an acute exacerbation of asthma, but were not hospitalised.
      Sample size was defined a priori for a study power of 90%. MAIN OUTCOME MEASURES:
      Difference in proportion of children who were symptom-free at Day 7, as measured
      by intention-to-treat (ITT) and per-protocol analysis; quality of life (QOL) on
      Days 7 and 14. RESULTS: 201 children were enrolled, and there was an 82%
      completion rate. There was no difference between groups in the proportion of
      children who were symptom-free (observed difference, 0.04 [95% CI, - 0.09 to
      0.18] by ITT analysis; 0.04 [95% CI, - 0.17 to 0.09] by per-protocol analysis).
      There was also no difference between groups in QOL (P = 0.42). The difference
      between groups for the primary outcome was within the equivalence range
      calculated post priori. CONCLUSION: A 5-day course of oral prednisolone confers
      no advantage over a 3-day course for children with asthma exacerbations who are
      not hospitalised. TRIAL REGISTRATION: Australian Clinical Trials Registry
      ACTRN012605000305628.

PMID- 18803533
TI  - Knowledge and attitudes of men about prostate cancer.
AB  - OBJECTIVE: To ascertain the current level of understanding among older men about
      prostate cancer, including treatment options and their potential side effects.
      DESIGN AND SETTING: Questionnaires administered by general practitioners in five
      general practices in the Perth metropolitan and regional areas of Western
      Australia. PARTICIPANTS: Convenience sample of 503 men aged 40-80 years, with or
      without prostate cancer, presenting for routine consultations between January and
      August 2006. MAIN OUTCOME MEASURE: Knowledge and attitudes of men about prostate
      cancer, and predictors of knowledge. RESULTS: Eighty per cent of men did not know
      the function of the prostate, and 48% failed to identify prostate cancer as the
      most common internal cancer in men. Thirty-five per cent had no knowledge of the
      treatments for prostate cancer and 53% had no knowledge of the side effects of
      treatments. Asked how they would arrive at a decision about treatment, 70% said
      they would ask the GP or specialist for information on all their options and then
      decide themselves. CONCLUSION: There is a deficit in knowledge about prostate
      cancer among men in the at-risk age group, encompassing areas that could delay
      diagnosis and treatment. Overall, the men preferred some GP or specialist
      involvement in treatment decision making.

PMID- 18803534
TI  - Prostate cancer and prostate-specific antigen testing in New South Wales.
AB  - OBJECTIVE: To describe trends in prostate-specific antigen (PSA) testing,
      prostate cancer incidence and mortality in New South Wales. DESIGN AND SETTING:
      Descriptive analysis using routinely collected data of observed trends in PSA
      testing from 1989 to 2006, and prostate cancer cases and deaths from 1972 to 2005
      in NSW. MAIN OUTCOME MEASURES: Age-standardised and age-specific rates and
      joinpoint regression to identify changes in trends; projected trends observed
      before the introduction of PSA testing to quantify its impact on incidence and
      mortality rates. RESULTS: The number of PSA tests per year more than doubled
      between 1994 and 2006. Age-standardised incidence of prostate cancer peaked in
      1994, fell by 10.0% per year to 1998 and then increased by 4.9% per year from
      2001 to 2005. An estimated 19 602 (43%) more men than expected from preceding
      trends were diagnosed with prostate cancer between 1989 and 2005 after PSA
      testing was introduced. The incidence of recorded advanced prostate cancer at
      diagnosis fell from 13.0 per 100,000 men in 1987-1991 to 7.0 per 100,000 men in
      2002-2005. The age-standardised mortality from prostate cancer increased by 3.6%
      per year between 1984 and 1990 and then fell by 2.0% per year to 2005.
      CONCLUSIONS: There was a sustained increase in prostate cancer incidence in NSW
      after PSA testing was introduced. While falls in the incidence of advanced
      disease at diagnosis and mortality from prostate cancer after 1993 are consistent
      with a benefit from PSA testing, other explanations cannot be excluded.

PMID- 18803535
TI  - How do the Australian guidelines for lipid-lowering drugs perform in practice?
      Cardiovascular disease risk in the AusDiab Study, 1999-2000.
AB  - OBJECTIVE: To determine how well the current Pharmaceutical Benefits Scheme (PBS)
      eligibility criteria for subsidy of lipid-lowering drugs compare with current
      national guidelines for determining the population at high risk of developing
      cardiovascular disease (CVD). DESIGN AND PARTICIPANTS: Analyses of the population
      based, cross-sectional Australian Diabetes, Obesity and Lifestyle (AusDiab)
      study, conducted in 1999-2000. The 1991 Framingham risk prediction equation was
      used to compute 5-year risk of developing first-time CVD in 8286 participants
      aged 30-74 years with neither CVD nor diabetes. Based on the National Heart
      Foundation of Australia and Cardiac Society of Australia and New Zealand
      guidelines, people with either 5-year CVD risk > or = 15% or with 5-year CVD risk
      of 10%-< 15% and the metabolic syndrome were defined as having estimated high
      absolute CVD risk. MAIN OUTCOME MEASURES: 5-year CVD risk; estimated population
      with high CVD risk. RESULTS: Among participants without prevalent CVD or
      diabetes, 7.9% of men and 1.5% of women had a 5-year CVD risk > or = 15%. Of the
      estimated residential Australian population in 2000 aged 30-74 years without CVD
      or diabetes, 717 000 people were considered to be at high absolute CVD risk.
      Among the high-risk AusDiab participants without CVD or diabetes, only 16.9% of
      men and 15.4% of women were being treated with lipid-lowering drugs. Of the 9.6%
      of participants free of CVD and diabetes who were untreated but eligible for
      subsidy under PBS criteria, only 27.4% had an estimated high absolute CVD risk.
      CONCLUSION: Strategies for CVD prevention using lipid-lowering medications can be
      improved by adoption of the absolute-risk approach.

PMID- 18803536
TI  - Staphylococcal pyomyositis in a temperate region: epidemiology and modern
      management.
AB  - OBJECTIVES: To describe all cases of staphylococcal pyomyositis in the Geelong
      region of Victoria over 110 months, to estimate the incidence of this disease,
      and to describe the clinical outcomes and identify any predisposing factors.
      DESIGN, PARTICIPANTS AND SETTING: A prospective case series identified by
      clinical features (local pain and fever) and magnetic resonance imaging (MRI)
      findings (hyperintense signal on T2-weighted scan), among patients presenting to
      Geelong Hospital, Victoria between 1 April 1998 and 1 June 2007. MAIN OUTCOME
      MEASURES: Estimation of incidence, clinical course and identification of
      predisposing factors. RESULTS: We estimate an annual incidence of 0.5 cases per
      100 000 person-years, and propose a recent history of vigorous exercise (six of
      11 patients) and underlying skin condition (five of 11 patients) as possible
      predisposing factors. MRI showed eight patients had osteomyelitis and one had
      septic arthritis. All patients had bacteraemia and one had mitral valve
      endocarditis. The duration of intravenous antibiotic therapy varied between 4 and
      12 weeks, and all patients were completely cured. CONCLUSION: Pyomyositis should
      be considered in patients presenting with local pain, fever, muscle tenderness,
      and a recent history of vigorous exercise or underlying skin condition. MRI may
      guide non-surgical management.

PMID- 18803537
TI  - High levels of confusion for cholesterol awareness campaigns.
AB  - Earlier this year, two industry-sponsored advertising campaigns for cholesterol
      awareness that target the general public were launched in Australia. These
      campaigns aimed to alert the public to the risks associated with having high
      cholesterol and encouraged cholesterol testing for wider groups than those
      specified by the National Heart Foundation. General practitioners should be aware
      of the potential for the two campaigns to confuse the general public as to who
      should be tested, and where. The campaign sponsors (Unilever Australasia and
      Pfizer) each have the potential to benefit by increased market share for their
      products, and increased profits. These disease awareness campaigns are examples
      of what is increasingly being termed "condition branding" by pharmaceutical
      marketing experts.

PMID- 18803538
TI  - The viability of Australia's teaching hospitals.
AB  - In a now diverse range of teaching hospitals striving to excel, excellence in
      research should be prioritised.

PMID- 18803539
TI  - Rediscovering university teaching hospitals for Australia.
AB  - Partnership between research and health services has a long history in other
      countries, but has been relatively recent in Australia, with several models
      arising in the 1960s and 1970s as research-based specialties developed. Since the
      implementation of Medibank, which became Medicare, Australian Health Care
      Agreements have been primarily crafted on the basis of transactional numbers,
      ignoring the need for links with teaching and research and the need to implement
      new developments. Education and research have been seen as the responsibility of
      the federal government, and hospitals are progressively less recognised or funded
      for these functions by the states. Australia's teaching hospitals are in danger
      of falling seriously behind those in other countries and losing their capacity to
      monitor quality, to innovate and to branch into new strategies in partnership
      with primary care services. We should look at initiatives in other countries such
      as the United Kingdom and Canada, which are making big strides in tackling
      similar issues. University hospitals hold the key, if appropriately linked with
      other services. The current Australian Health Care Agreements are on hold. A new
      agency is needed to support clinical and service-related research, with a new
      structure and track for federal government funding, and providing oversight of
      research and development, of clinical governance and quality of outcomes in
      health care, linked with new strategies for prevention and treatment. A component
      of the foreshadowed additional federal government funding for health should be
      sequestered to set up such an agency.

PMID- 18803540
TI  - Coeliac disease in an Indian patient: an important diagnosis to consider.

PMID- 18803541
TI  - Lead poisoning and Burton's line.

PMID- 18803542
TI  - Functional improvement of the Australian health care system - can rehabilitation
      assist?
AB  - Strategies for managing increasing health system demand have focused on the acute
      sector and chronic disease management in the community, with little attention on
      the role of rehabilitation. There were over 53 000 inpatient rehabilitation
      episodes in Australia in 2006. We argue that rehabilitation can improve patient
      flow and outcomes in acute care if engaged early. The effectiveness of
      rehabilitation can be enhanced by increasing the intensity of therapy and
      developing models of rehabilitation that provide alternatives to inpatient care.
      Factors that reduce the efficiency of rehabilitation services include the
      location of many services in small, stand-alone hospitals without acute support;
      the lack of options for managing younger people with acquired disability in the
      community; and deficiencies in government programs for the supply of aids,
      equipment and home modifications. Improving the organisation of rehabilitation
      services should improve access to acute and rehabilitation inpatient beds,
      improve patient outcomes and reduce costs.

PMID- 18803543
TI  - Will Australian rural clinical schools be an effective workforce strategy? Early
      indications of their positive effect on intern choice and rural career interest.

PMID- 18803544
TI  - Is Australia headed for an epidemic of nicotine replacement therapy addicts?

PMID- 18803545
TI  - Consent in paediatric research: an evaluation of the guidance provided in the
      2007 NHMRC National statement on ethical conduct in human research.

PMID- 18803546
TI  - The prevention and management of herpes zoster.

PMID- 18803547
TI  - What has happened to clinical leadership in futile care discussions?

PMID- 18803548
TI  - Anorexia nervosa and senna misuse: nephrocalcinosis, digital clubbing and
      hypertrophic osteoarthropathy.

PMID- 18803549
TI  - Impact of specialty on attitudes of Australian medical practitioners to end-of
      life decisions.

PMID- 18803550
TI  - Management of adrenal insufficiency during the stress of medical illness and
      surgery.

PMID- 18803551
TI  - Premature ejaculation: a clinical update.

PMID- 18803552
TI  - Glycolysis in Ustilago maydis.
AB  - The kinetic parameters of the 10 glycolytic enzymes and glycolytic fluxes were
      determined for the first time in Ustilago maydis. Enzyme activities in yeast
      grown in minimal medium and harvested in the stationary stage were twofold higher
      than those from yeast grown in rich medium. In contrast, in yeast harvested in
      the exponential stage, the enzyme activities were higher in cells grown in rich
      medium. Phosphofructokinase activity was the lowest in the four culture
      conditions analyzed, suggesting that this enzyme is a flux-controlling step in U.
      maydis glycolysis. The V(max) and K(m) values of hexokinase and pyruvate kinase
      were similar under all conditions. The results revealed that U. maydis aldolase
      belongs to the class II type of metalo-aldolases. 3-Phosphoglycerate mutase
      (PGAM) activity was 2,3-bisphosphoglycerate cofactor independent, which
      contrasted with the cofactor dependency predicted by the amino acid sequence
      alignment analysis. Pyruvate was secreted by U. maydis yeast in the presence and
      absence of external glucose. The glycolytic enzyme activities in the U. maydis
      mycelial form were similar to those found in yeast, except for one order of
      magnitude higher phosphofructokinase and PGAM activities, thus suggesting
      differences in the glycolysis regulatory mechanisms between the two cellular
      forms.

PMID- 18803553
TI  - Menorrhagia and reproductive health in rare bleeding disorders: a study from the
      Indian subcontinent.
AB  - At this centre, 130 women with rare bleeding disorders (RBD) were investigated
      over the past 15 years. Fifty patients were above the age of menarche (age of
      menarche in India is 10 years). Of these 44 presented with menorrhagia. Other
      complications in these patients involved bleeding because of ruptured graffian
      follicle (1), severe haemorrhage following caesarean section (1), recurrent
      pregnancy losses (3), hysterectomy to control menorrhagia (2), laser ablation of
      endometrium (1) and irradiation of ovary (1). Three patients voluntarily chose to
      remain unmarried because of the problems associated with menorrhagia which they
      assumed will interfere with married life. All the 45 patients had iron deficiency
      anaemia. The spectrum of RBD in these patients comprised Glanzmann's
      thrombasthenia (17), Bernard-Soulier syndrome (2), storage pool disorder (2),
      factor V (FV) deficiency (3), combined FV and factor VIII deficiency (5), factor
      XI deficiency (3), factor XIII deficiency (1), factor X deficiency (5), factor
      VII deficiency (2), alpha(2)-antiplasmin deficiency (1) and afibrinogenemia (3).
      RBD in women is diagnosed late and often they are not optimally managed hence
      suffer both iatrogenic and non-iatrogenic complications in this country.

PMID- 18803554
TI  - Recombinant human TSH increases the efficacy of a fixed activity of radioiodine
      for treatment of multinodular goitre.
AB  - CONTEXT: High doses of (131)I are usually needed in the treatment of multinodular
      goitre (MNG) for effective thyroid volume (TV) reduction. Recombinant human
      thyroid-stimulating hormone (rhTSH) is an adjuvant to enhance (131)I uptake,
      allowing a decrease in radiation activity and enhancing (131)I efficacy.
      OBJECTIVE: To evaluate whether rhTSH increases the efficacy of a fixed activity
      of (131)I for the treatment of MNG. DESIGN: Two-year, observational, placebo
      controlled study. SETTING: Patients received 0.1 mg rhTSH (A), 0.005 mg rhTSH (B)
      or placebo (C). A fixed activity of 1.11 GBq of (131)I was administered 24 h
      after rhTSH or placebo. PATIENTS: A total of 28 outpatients (26 females and two
      males) with MNG. MEASUREMENTS: TSH, free T4, T3, thyroglobulin (Tg) and TV.
      RESULTS: Basal radioactive iodine uptake and TV values were comparable among all
      groups. After rhTSH or placebo, peak levels of TSH, free T4, T3 and Tg were
      higher in A than in B or in C (p < 0.05). Hyperthyroidism was observed in A (n =
      2), B (n = 6) and C (n = 4). Thyroid enlargement was reported in A (n = 3) and B
      (n = 6). After 24 months, 10 patients developed hypothyroidism (four in A, three
      in B and three in C). TV reduction was similar between A and B (37.2 +/- 25.5%
      vs. 39.3 +/- 27.9%, p = 0.88), but different from the non-significant reduction
      in C (15.3 +/- 28.3%, p = 0.08). CONCLUSIONS: Followed by 1.11 GBq, a very low
      dose of 0.005 mg rhTSH was equally safe and effective as 0.1 mg rhTSH. Both doses
      increased the efficacy of radioiodine. Adverse events were mild, transient and
      readily treatable.

PMID- 18803556
TI  - Tako-tsubo-like left ventricular dysfunction: transient left ventricular apical
      ballooning syndrome.
AB  - AIMS/OBJECTIVES: This review examines the 'tako-tsubo-like' syndrome or transient
      left ventricular apical ballooning. The aim of this review is a complete
      evaluation of epidemiology, clinical and instrumental features,
      pathophysiological mechanisms, therapy and prognosis of this syndrome. METHODS:
      We have evaluated the data from literature for a comprehensive consideration of
      multiple aspects of this syndrome. RESULTS/FINDINGS: Transient left ventricular
      apical ballooning typically affects women, and the clinical presentation is
      comparable to acute coronary syndrome with chest pain or sudden dyspnoea, changes
      in ECG and elevated cardiac enzymes in the absence of significant coronary
      stenosis, with complete resolution of wall-motion abnormalities in a period of
      days or weeks. This syndrome is triggered by marked psychological or
      physiological stress. Several pathophysiological mechanisms have been proposed,
      such as cathecolamine-mediated cardiotoxicity, abnormalities in coronary
      microvascular function and multivessel coronary vasospasm. The highest incidence
      of transient left ventricular apical ballooning is in the Japanese population,
      but it has been recently identified also in the USA and Europe. Treatment is
      empirical and supportive. The prognosis is generally favourable, although some
      deaths have been reported, usually the result of irreversible cardiogenic shock,
      refractory ventricular arrhythmias, or other catastrophic cardiovascular event.
      CONCLUSIONS/INTERPRETATIONS: We conclude by emphasising the importance of a more
      deeper knowledge of this syndrome for general physicians and cardiologists and it
      should be often considered as a possible diagnosis occurring in emergency
      department and in patients admitted in the Chest Pain Units with a diagnosis of
      coronary acute syndrome.

PMID- 18803555
TI  - A retrospective database study comparing treatment outcomes and cost associated
      with choice of fixed-dose inhaled corticosteroid/long-acting beta-agonists for
      asthma maintenance treatment in Germany.
AB  - AIMS: This retrospective, observational cohort study aimed to compare treatment
      outcomes and healthcare costs in the year after initiation of maintenance
      treatment with budesonide/formoterol or salmeterol/fluticasone in a German
      healthcare setting. METHODS: Data on German asthma patients initiating treatment
      with budesonide/formoterol or salmeterol/fluticasone between June 2001 and June
      2005 were obtained from the IMS Disease Analyzer database. The primary outcome
      was the probability of treatment success, defined according to short-acting
      beta(2)-agonist prescriptions and switches or addition of controller medications,
      during the postindex year. A secondary definition of treatment success included
      hospitalisations and oral corticosteroid (OCS) prescriptions. Secondary outcomes
      included severe asthma exacerbations, defined as >or=1 OCS prescription, asthma
      related hospitalisation and/or referral. The effect of treatment on costs was
      estimated using generalised linear models, adjusting for patient and physician
      characteristics. RESULTS: There were no significant differences between the
      budesonide/formoterol (n = 1456) and salmeterol/fluticasone (n = 982) groups in
      disease severity markers in the pre-index year. Patients on budesonide/formoterol
      had a 44% greater probability of treatment success [odds ratio (OR): 1.44; p =
      0.0003] according to the primary definition and a 26% greater probability (OR:
      1.26; p = 0.0119) according to the secondary definition, fewer severe
      exacerbations (-33.4%; p = 0.0123) and fewer OCS prescriptions (-31.5%; p =
      0.0082) compared with salmeterol/fluticasone, after controlling for baseline
      characteristics. Adjusting for covariates, budesonide/formoterol had a
      significant inverse relationship on asthma-related costs compared with
      salmeterol/fluticasone (-13.4%; p < 0.001). Total cost (asthma- and non-asthma
      related costs) was 12.6% lower for budesonide/formoterol (p < 0.0001).
      CONCLUSION: This study suggests that for patients with chronic asthma in Germany,
      budesonide/formoterol rather than salmeterol/fluticasone had a higher likelihood
      of treatment success, and that budesonide/formoterol is the less costly option.
      Although the cohorts appeared to be well matched at baseline, the results should
      be interpreted with caution given the observational nature of the study.

PMID- 18803557
TI  - Thyroid fine needle aspiration biopsy: is topical local anaesthesia beneficial?
AB  - OBJECTIVE: Thyroid fine needle aspiration biopsy (TFNAB) is the gold standard in
      the differential diagnosis of the thyroid nodules. In general, no analgesia is
      needed before this procedure. However, it is usually believed that the patients
      may be more comfortable if the procedure is performed under local anaesthetics.
      In this study, we examined the impact of the use of dermal anaesthetic on the
      patient's level of discomfort during palpation-guided TFNAB. METHODS: Fifty
      female patients with nodular goitre were enrolled in this study. Patients were
      randomised into two groups: a placebo cream was applied to group 1 patients (25
      females; mean age 47.45 +/- 11.61 years), and local anaesthesia (EMLA 5% cream)
      was applied to group 2 patients (25 females; mean age 50.89 +/- 12.01 years)
      approximately 1 h before TFNAB. All patients were asked to mark the pain they
      felt during the TFNAB on Visual Analogue Scale. RESULTS: The pain scores during
      TFNAB were 27.73 +/- 20.01 mm and 24.79 +/- 21.98 mm in the placebo group and in
      the EMLA group respectively. There was no significant difference between the
      groups (p = 0.496). CONCLUSIONS: Topical anaesthesia before palpation-guided
      TFNAB provides no benefit.

PMID- 18803558
TI  - Chondrichthyans have a bulbus arteriosus at the arterial pole of the heart:
      morphological and evolutionary implications.
AB  - It has been generally assumed that the outflow tract of the chondrichthyan heart
      consists of the conus arteriosus, characterized by cardiac muscle in its walls.
      However, classical observations, neglected for many years, indicated that the
      distal component of the cardiac outflow tract of several elasmobranch species was
      composed of tissue resembling that of the ventral aorta. The present study was
      outlined to test the hypothesis that this intrapericardial, non-myocardial
      component might be homologous to the actinopterygian bulbus arteriosus. The
      material consisted of Atlantic catshark adults and embryos, which were examined
      by means of histochemical and immunohistochemical techniques for light and
      fluorescence microscopy. In this species, the distal component of the outflow
      tract differs histomorphologically from both the ventral aorta and the conus
      arteriosus; it is devoid of myocardium, is covered by epicardium and is crossed
      by the coronary arterial trunks. In the embryonic hearts examined, this distal
      component showed positive reactivity for 4,5-diaminofluorescein 2-diacetate (DAF
      2DA), a fluorescent nitric oxide indicator. These findings, together with other
      observations in holocephals and several elasmobranch species, confirm that
      chondrichthyans possess a bulbus arteriosus interposed between the conus
      arteriosus and the ventral aorta. Therefore, the primitive heart of
      gnathostomates consists of five intrapericardial components, sinus venosus,
      atrium, ventricle, conus arteriosus and bulbus arteriosus, indicating that the
      bulbus arteriosus can no longer be regarded as an actinopterygian apomorphy. The
      DAF-2DA-positive reactivity of the chondrichthyan embryonic bulbus suggests that
      this structure is homologous to the base of the great arterial trunks of birds
      and mammals, which derives from the embryonic secondary heart field.

PMID- 18803559
TI  - The trials and tribulations of fibrillation ablation.

PMID- 18803560
TI  - Arrhythmias in children having a single left superior vena cava and minimal
      structural heart disease.
AB  - BACKGROUND: The presence of a single left superior vena cava in the absence of
      complex congenital heart disease is uncommon, and, in the absence of hemodynamic
      consequences, it would not be expected to result in cardiovascular signs or
      symptoms. Single case reports and our anecdotal experience suggested to us that
      this anomaly is highly associated with cardiac arrhythmias. OBJECTIVE: We sought
      to describe the clinically important arrhythmias in a population of young
      patients having this anomaly. METHODS: A retrospective chart review was performed
      from all patients <20 years old and who were determined by echocardiography over
      an 11-year-period to have a single left superior vena cava and minor or no
      coexisting congenital heart defects. The prevalence of nonsinus pacemaker, age
      corrected sinus rate percentile, and prevalence of brady- or tachyarrhythmias was
      compared with a control group of patients having bilateral superior vena cavae.
      RESULTS: Eight patients having a single left and 55 patients having bilateral
      superior vena cava(e) were identified. The existence of this anomaly tended to be
      associated with a lower age-corrected sinus rate percentile (17.5% vs 75%, P =
      0.09), and was associated with a higher prevalence of arrhythmias (50% vs 7%, P =
      0.014) compared with the control group. In the study group, one patient each had
      clinically relevant sinus node dysfunction, third-degree AV block, Wolff
      Parkinson-White syndrome and atrial fibrillation, and AV nodal reentrant
      tachycardia. CONCLUSION: Even in the absence of symptoms, patients found to have
      a single left superior vena cava should be monitored long-term for clinically
      important arrhythmias.

PMID- 18803561
TI  - Right ventricular pressure changes during induced ventricular tachycardias
      predict clinical symptoms of cerebral hypoperfusion: implications for a reduction
      of unnecessary, painful ICD shocks.
AB  - BACKGROUND: ICD shocks occurring in conscious patients (as in the case of well
      tolerated arrhythmias, electromagnetic interference, or oversensing) have a
      deleterious impact on the quality of life. We evaluated if a hemodynamic
      parameter, calculated from the right ventricular pressure (RVP) or systemic
      arterial pressure (AP) signals, could predict early clinical symptoms of cerebral
      hypoperfusion during induced ventricular tachycardias (VTs). METHODS AND RESULTS:
      We analyzed 42 tolerated (no symptoms) and 30 untolerated (syncope or severe
      symptoms within 30 seconds from the onset) VTs, induced during
      electrophysiological study. The cycle length (CL) and the hemodynamic data (mean
      AP and RVP, arterial pulse pressure and RV pulse pressure, and maximum AP and RVP
      dP/dT) were automatically sampled in two VT epochs: the "detection" window, from
      beat 24 to 32, and the "preintervention" window, immediately before the first
      therapeutic attempt. Although the CL and all the hemodynamic parameters
      (expressed as % change versus pre-VT values) were significantly lower in
      untolerated versus tolerated VTs both at detection and preintervention (with the
      exception of the mean RVP which progressively increased in both groups), ROC
      analysis demonstrated that only the preintervention RV pulse pressure showed no
      overlap between groups, providing 100% sensitivity and positive predictive value.
      CONCLUSIONS: The reduction of the RV pulse pressure is a better predictor of
      early cerebral symptoms than CL or other hemodynamic indexes during induced VTs.
      Since long-term RVP monitoring is feasible, this parameter could be incorporated
      into ICDs decisional path, in the perspective of reducing unnecessary, painful
      shocks.

PMID- 18803562
TI  - Safety profiles and lesion size of different radiofrequency ablation
      technologies: a comparison of large tip, open and closed irrigation catheters.
AB  - INTRODUCTION: Different technologies have been developed for radiofrequency
      ablation (RFA), which include increasing electrode (tip) size and cooling the tip
      through irrigation either internally (closed-loop) with D5W or externally (open
      loop) with saline. Although these catheters are widely used clinically, the
      propensity for adverse events and the lesion profiles of each of these catheter
      technologies have not been directly compared under a wide range of controlled
      conditions. METHODS AND RESULTS: Freshly excised canine thigh muscle was placed
      in a chamber filled with circulating, heparinized blood heated to 37 degrees C.
      Five different catheters were tested: 4 mm tip, 10 mm tip single thermistor, 10
      mm tip multitemperature sensor, 4 mm closed-loop irrigated cooled-tip, and 4 mm
      open-loop irrigated cooled tip at several different contact and power settings.
      The catheter and tissue interface was continuously monitored with intracardiac
      echocardiography (echo) (Acuson). During the RFA, any bubbling generated from the
      tip and/or popping seen on echo was noted, and after each RFA, the catheter and
      lesion were examined for the presence of thrombus. For all of the catheters,
      complications correlated to the electrode tip temperature and power setting. All
      of the catheters experienced complications at any lesion size except for the open
      irrigated catheter, which only had complications at the largest lesions. Overall,
      the cooled tip catheters experienced an at least sixfold greater odds of popping,
      bubbling, and impedance rises than the 4 mm, but the majority occurred at power
      levels greater than 20 W. The open-irrigated catheters created eccentric lesions
      that extended away from the tissue-catheter interface, in the direction of blood
      flow. In addition, it produced saline filled blisters at the lesion site in 16.7%
      of the burns. The 10 mm catheter had an at least twofold greater odds of
      thrombus, charring, and bubbling, but larger lesions than the 10 mm
      multitemperature sensor catheter. CONCLUSIONS: Catheter type, contact conditions,
      and power settings all play a role in lesion size and in the frequency of
      complications that occur during an RFA. Cooling the electrode tip, either
      internally or externally, does not prevent complications from occurring,
      especially at the higher power control settings. Adding more temperature sensors
      to the 10 mm seems to reduce the amount of complications that can occur.

PMID- 18803563
TI  - Full-color direct visualization of the atrial septum to guide transseptal
      puncture.
AB  - INTRODUCTION: Transseptal puncture is required for many interventional procedures
      but has a serious complication rate of approximately 1%-primarily related to
      misidentification of the fossa ovalis resulting in inadvertent puncture of other
      cardiac structures. We investigated the utility of a full color visualization
      catheter to correctly position and guide transseptal puncture of the fossa
      ovalis. METHODS AND RESULTS: Transseptal puncture and left atrial cannulation
      were performed after visualization of the atrial septum and fossa ovalis with the
      visualization catheter (IRIS, Voyage Medical Inc.) on six swine. For each animal,
      the transseptal puncture was performed twice and the catheter was examined for
      clot after each puncture. The 12 transseptal punctures required 6.8 +/- 3.6
      minutes procedural time and 300 +/- 94 mL of fluid administered per procedure
      (i.e., two punctures). IRIS visualization of the atrial septum correlated well
      with postmortem examination of the atrial septum. In the three animals in which a
      patent foramen ovale was present (as confirmed by pathological examination), it
      was also correctly identified by in vivo visualization using the IRIS catheter.
      CONCLUSION: The IRIS catheter allows direct in vivo visualization of the
      interatrial septum to guide transseptal puncture of previous punctures.

PMID- 18803564
TI  - Cost comparison of ablation versus antiarrhythmic drugs as first-line therapy for
      atrial fibrillation: an economic evaluation of the RAAFT pilot study.
AB  - INTRODUCTION: Radiofrequency ablation (RFA) has become an accepted therapy for
      atrial fibrillation (AF). The objective of this study was to perform an economic
      evaluation of RFA versus antiarrhythmic drug therapy (AAD) as first-line
      treatment of symptomatic paroxysmal AF. METHODS: To estimate and compare the
      costs of RFA versus AAD, a decision analytic model was developed using data on AF
      recurrence, hospitalization rates, AAD use, and treatment crossover rates derived
      directly from the Randomized Trial of RFA versus AAD as First-Line Treatment of
      Symptomatic Atrial Fibrillation (RAAFT). Resource utilization was modeled to
      reflect Canadian clinical practice in AF management. Unit costs of healthcare
      interactions were based on available Canadian government resources and published
      literature. Costs were assessed based on intention-to-treat. Total expected costs
      were computed to include initial treatment, hospital stay, physician fees,
      diagnostic tests, and outpatient visits. Sensitivity analyses were performed to
      account for the uncertainties. The study was conducted from the third party
      payer's perspective and costs are reported in 2005 Canadian dollars with 3%
      discount rate used in the analysis. RESULTS: During the 2-month blanking period
      following therapy selection, total average costs for RFA and AAD were $10,465 and
      $2,556, respectively; at 1-year follow-up, these were $12,823 and $6,053; and
      total 2-year cumulative total average costs were $15,303 and $14,392. Sensitivity
      analyses did not alter the results, suggesting the model is robust. CONCLUSIONS:
      RFA as first-line treatment strategy in patients with symptomatic paroxysmal AF
      was cost neutral 2 years after the initial procedure compared to AAD.

PMID- 18803565
TI  - Noncontact mapping of the heart: how and when to use.
AB  - The noncontact mapping system is a new tool for electrophysiologic study and
      radiofrequency ablation. The mode of operation includes single beat, three
      dimensional, high-density mapping. Careful analysis of unipolar electrograms and
      isopotential maps are essential to understand the mechanism of the arrhythmia.
      Radiofrequency catheter ablation guided by this system is effective in curing
      patients of their tachycardias.

PMID- 18803566
TI  - Hemodynamic monitoring during syncope: utility and limitations.

PMID- 18803567
TI  - Acute results of pulmonary vein isolation in patients with paroxysmal atrial
      fibrillation using a single mesh catheter.
AB  - INTRODUCTION: Catheter-based pulmonary vein isolation (PVI) is an established
      therapy to treat patients with paroxysmal atrial fibrillation. We evaluated the
      efficacy of a simplified interventional procedure for PVI by using a single mesh
      catheter for mapping as well as ablation and with guidance of fluoroscopic
      imaging only. METHODS AND RESULTS: Forty-eight patients with paroxysmal atrial
      fibrillation were screened by cardiac computed tomography for their anatomical
      suitability to undergo PVI with the high-density mesh ablator catheter as the
      only left atrial device. The procedure was performed in 26 patients (12 males,
      mean age 61 years) who met the criteria of four clearly separated pulmonary veins
      (PVs) with an ostial diameter of 15-25 mm. No three-dimensional mapping systems
      or additional ablation devices were used. In all 26 patients, all four PVs could
      be accessed and mapped with the high-density mesh ablator catheter. Electrical
      isolation was achieved in 99 of 102 (97%) of the pulmonary veins that revealed PV
      potentials. Mean total procedure time and fluoroscopy time were 187 +/- 36
      minutes and 34.6 +/- 10.0 minutes, respectively. CONCLUSION: The single-catheter
      approach using the high-density mesh ablator catheter for mapping as well as
      ablation reveals a high acute success rate of PVI while, at the same time,
      reducing the complexity of the procedure, and the procedure time. Long-term data
      on clinical success are needed to justify this simplified approach.

PMID- 18803568
TI  - An unreported cause of pacemaker dysfunction: fracture of tines.

PMID- 18803569
TI  - Focal atrial tachycardia originating from the right atrial appendage: first
      successful cryoballoon isolation.
AB  - Focal atrial tachycardias (AT) can arise from the right atrial appendage (RAA).
      However, conventional catheter mapping and radiofrequency (RF) ablation inside
      the RAA is associated with the risk of cardiac perforation. The cryoballoon
      catheter represents a novel ablation device that was originally developed to
      facilitate pulmonary vein isolation. This report describes the first successful
      RAA isolation using a cryoballoon in a patient with an incessant focal RAA AT
      despite previous irrigated tip endo- and epicardial ablation attempts. Further,
      cryoballoon ablation targets beyond pulmonary veins may evolve.

PMID- 18803570
TI  - CaMKII and its role in cardiac arrhythmia.
AB  - Calcium/calmodulin-dependent kinase II (CaMKII) is a multifunctional
      serine/threonine kinase widely distributed in a number of tissue types.
      Activation of CaMKII has been linked to important downstream physiological
      processes, including apoptosis, hypertrophy, and arrhythmia in the heart.
      Pharmacological or genetic inhibition of CaMKII has been shown to improve health
      outcomes in a number of animal models. In this review, we summarize the
      structural and functional properties of CaMKII and detail its role in cardiac
      arrhythmia, structural heart disease, and sudden death.

PMID- 18803571
TI  - The impact of myocardial viability on the clinical outcome of cardiac
      resynchronization therapy.
AB  - INTRODUCTION: Around 30% of patients do not respond to cardiac resynchronization
      therapy (CRT). Nonischemic cardiomyopathy has been identified as an independent
      predictor of response to CRT, probably due to the absence of compact scar.
      METHODS AND RESULTS: The relationship between cardiac scar, ischemia, and
      hibernation (both at the left-ventricular pacing site and as a total burden) and
      response to CRT was studied in patients with ischemic cardiomyopathy using the
      perfusion-viability positron emission tomography (PET) test. Sixty-six patients
      with ischemic cardiomyopathy and traditional criteria for CRT were included. All
      patients underwent PET scan prior to CRT. Using PET, the amount and location of
      scarred, ischemic, and hibernating myocardium were characterized. No
      revascularization was indicated. Responders were defined by an improvement of
      left-ventricular ejection fraction (LVEF) >or= 5% and/or New York Heart
      Association (NYHA) class >or= 1 degree. During a mean follow-up of 26.2 +/- 22.2
      months, there was a significant improvement in NYHA class and reverse remodeling
      in patients with the LV lead inserted remotely from the scar. However, reverse
      remodeling of a similar degree was present also in patients with extensive
      scarring including the lateral wall. The presence of ischemia, hibernation, or
      nontransmural scar at the pacing-site did not significantly modify the outcome of
      CRT as compared with viable myocardium. There were only 38% of CRT-nonresponders.
      Neither the extent of scar, ischemia, hibernation, or viability predicted outcome
      or mortality. Twenty patients died during the follow-up, one patient underwent
      heart transplant. CONCLUSIONS: At follow-up, response to CRT is observed
      regardless of the presence of extensive scarring. Left ventricular (LV) pacing at
      sites with ischemia, hibernation, or nontransmural scar does not appear to modify
      the effect of CRT as compared to viable tissue.

PMID- 18803572
TI  - The role of cardiac resynchronization therapy in the young.

PMID- 18803574
TI  - To replace or not to replace: a systematic approach to respond to device
      advisories.
AB  - AIM: The decision of whether and when to replace a device in response to an
      "advisory" letter requires careful consideration, because device replacement
      carries related risks and is influenced by the clinical characteristics of the
      patient. METHODS AND RESULTS: The risk/benefit of device replacement depends on
      four parameters: expected annual sudden cardiac death rate; residual device life;
      difference in failure rate between the device listed on the advisory letter and
      the replacement device; and the replacement procedure mortality risk. Using these
      four factors, we have developed an equation that provides the "number needed to
      replace" (NNR) to save one life. Per our model, patients implanted with a device
      with a failure rate approaching 1% and a probability of requiring device
      intervention >or=25% per year-in particular, pacemaker-dependent patients-have an
      NNR <250. Pacemaker-dependent patients, with devices having three or more years
      longevity, but with device failure rates >or=0.5%, have an NNR <100. Patients
      with arrhythmic risk <or=2.5% per year and those with devices having failure
      rates <0.1% have a high NNR and stand more risk to be harmed than benefited from
      device replacement. CONCLUSIONS: Pacemaker-dependent patients and those with high
      arrhythmic risk (>or=25% annually) when having "advisory" devices with high
      failure rate (>or=1%) have an NNR <250 and, hence, could be considered for device
      replacement. Conversely, patients with arrhythmic risk <or=2.5% per year and
      those with devices having failure rates <or=0.1% have a high NNR or even risk of
      "harm" from device replacement. In all the intermediate cases, the NNR will
      quantify the benefit/risk ratio of replacement, thus helping physicians and
      patients decide on the preferred approach. The NNR methodology proposed here is
      also applicable to advisory notices issued to leads, but the high morbidity
      associated with lead replacement will generally rule out interventions to replace
      leads.

PMID- 18803575
TI  - Dilated left atrium and pulmonary veins in patients with calcified coronary
      artery: a potential contributor to the genesis of atrial fibrillation.
AB  - INTRODUCTION: Coronary artery disease (CAD) is an important etiology of atrial
      fibrillation (AF). Coronary artery calcification is a marker of coronary
      atherosclerosis and coronary events. The purpose of this study was to investigate
      whether larger left atrium (LA) and pulmonary veins (PVs) were seen by
      multidetector computed tomography (MDCT) scans in those patients with higher
      coronary calcium scores. METHODS AND RESULTS: A total of 166 patients undergoing
      MDCT for general check-up (n = 128, 77%) or suspected CAD (n = 38, 23%) were
      enrolled and divided into a control (calcium score = 0, n = 60), medium calcium
      score (calcium score = 100 approximately 400, n = 47), and high calcium score
      (calcium score >400, n = 59) groups. Diameters and areas of the LA, left atrial
      appendage (LAA), and PVs were measured by MDCT. The high calcium score group had
      significantly larger PVs diameters, LAA orifice area (1.9 +/- 1.4 cm(2), 0.9 +/-
      0.5 cm(2), 0.8 +/- 0.4 cm(2), P < 0.005), LA anterior-posterior distance (32.2 +/
      6.8 mm, 30.4 +/- 6.5 mm, 27.3 +/- 6.0 mm, P < 0.05), and transverse distance
      (52.6 +/- 7.3 mm, 50.2 +/- 9 mm, 49.5 +/- 4.6 mm, P < 0.05) than the medium
      calcium score and control groups. Six (3.6%) patients with paroxysmal AF had
      higher calcium scores and larger diameters of LA, LAA, and PVs than those (96.4%)
      without paroxysmal AF. Two patients in the high calcium score group had calcified
      PVs localized to the right upper and left upper PVs. The incidence of calcified
      PVs was 1.2% for the total patients and 3.3% for the high calcium score patients.
      CONCLUSION: In the presence of high calcium scores in this patient population,
      the LA, LAA, and PVs were enlarged.

PMID- 18803576
TI  - Biopsychosocial functioning of women after mastectomy.
AB  - AIMS: The aim of this work was to identify the problems of women after total
      mastectomy and partial mastectomy with regard to various factors and intensity of
      discomfort which affect the quality of life. BACKGROUND: The loss of the
      attribute of femininity, maternity and sexuality, as the mammary gland is
      perceived by patients, is a highly traumatic experience, frequently resulting in
      re-evaluation of life and functioning to date. DESIGN AND METHODS: The survey
      encompassed 494 women after operational treatment of breast cancer with varying
      time since the procedure. The research group consisted of women after radical
      mastectomy, and the control group consisted of patients after partial mastectomy.
      RESULTS: The intensity of post-traumatic stress was an important factor affecting
      the level of depression and anxiety. This correlation appeared to be
      statistically highly significant in the group of women after total mastectomy.
      Life satisfaction, the level of depression and anxiety in women after such an
      operation were dependent on the intensity of post-traumatic stress and they
      caused inferior biopsychosocial functioning. CONCLUSIONS: Women after mastectomy
      require professional long-term support; this need should result in the
      enhancement of services provided in relevant women's support groups. RELEVANCE TO
      CLINICAL PRACTICE: When evaluating holistically the life of women after
      mastectomy, all spheres of everyday functioning should be taken into account:
      physical, cognitive, emotional and social.

PMID- 18803577
TI  - Views of xerostomia among health care professionals: a qualitative study.
AB  - AIM: To explore and describe views of xerostomia among health care professionals.
      BACKGROUND: Xerostomia (dry mouth) is caused by changes in quality and quantity
      of saliva due to poor health, certain drugs and radiation therapy. It is a common
      symptom, particularly among older people and has devastating consequences with
      regard to oral health and general well-being. METHODS: Data were obtained and
      categorised by interviewing 16 health care professionals. Qualitative content
      analysis was chosen as the method of analysis. DESIGN: Qualitative. RESULTS: The
      latent content was formulated into a theme: xerostomia is a well-known problem,
      yet there is inadequate management of patients with xerostomia. The findings
      identified three categories expressing the manifest content: awareness of
      xerostomia, indifferent attitude and insufficient support. CONCLUSIONS: Although
      xerostomia was recognised as commonly occurring, it was considered to be an
      underestimated and an ignored problem. Proper attention to conditions of
      xerostomia and subsequent patient management were viewed as fragmentary and
      inadequate. Additional qualitative studies among patients with xerostomia would
      be desirable to gain further understanding of the problems with xerostomia, its
      professional recognition and management. RELEVANCE TO CLINICAL PRACTICE: A
      holistic view, positive professional attitudes and enhanced knowledge of
      xerostomia seem essential to augment collaboration among health care
      professionals and to improve compassion for and support of patients with
      xerostomia.

PMID- 18803578
TI  - Viral exanthems in childhood--infectious (direct) exanthems. Part 1: Classic
      exanthems.
AB  - Exanthems during childhood occur quite often and are mostly harmless in nature.
      Among different trigger factors, viruses are of prime importance. Viral exanthems
      may manifest as a macular, maculopapular, papular, urticarial or vesicular rash.
      Exanthems with other causes (bacterial toxins, drugs, autoimmune diseases) as
      well as those with unclear etiology such as unilateral lat-erothoracic exanthem
      or Kawasaki disease must be differentiated from viral exanthems. This review
      focuses on the classic viral exanthems.

PMID- 18803580
TI  - Photodynamic therapy with 5-aminolaevulinic acid, dimethylsulfoxide and curettage
      in basal cell carcinoma: a 6-year clinical and histological follow-up.
AB  - BACKGROUND: Long-term follow-up data are needed to evaluate treatment effect
      after photodynamic therapy (PDT). OBJECTIVE: To investigate long-term clinical,
      histological and cosmetic follow-up results in basal cell carcinoma (BCC) after
      PDT, including treatment response related to patients and lesion characteristics.
      MATERIALS AND METHODS: A longitudinal study of 44 patients with 60 histologically
      verified BCC tumours, treated with one or two sessions of dimethylsulfoxide
      (DMSO)-supported 5-aminolaevulinic acid--PDT following curettage, was performed.
      Lesions in complete remission after 3 months were followed with clinical
      inspection, histological investigation and evaluation of cosmetic outcome at
      regular intervals; long-term efficacy assessed as verified recurrence within 72
      months after PDT. RESULTS: Complete remission at 3 months was achieved in 55
      lesions from 39 patients. Two patients with one lesion each died. At 72 months,
      43 of 53 lesions remained disease-free (81%); 68% remained after one treatment
      session, and 91% remained after two treatment sessions. Recurrence of tumour
      occurred at 6, 12, 24 and 36 months in 2, 4, 2 and 2 lesions, respectively;
      clinical investigation identified 97% of them. Male sex and H-mid-face zone were
      significantly associated with recurrence. The cosmetic outcome at 72 months was
      rated as good or excellent by patients and investigators in more than 90% of
      evaluated cases. CONCLUSION: DMSO-PDT following curettage is an effective
      treatment for BCC, with favourable long-term clinical, histopathological and
      cosmetic results. Clinical examination of treated lesions appears to be
      sufficient for long term follow up.

PMID- 18803582
TI  - Application of in situ detection techniques to determine the systemic condition
      of lymphocystis disease virus infection in cultured gilt-head seabream, Sparus
      aurata L.
AB  - Immunohistochemistry (IHC) and in situ hybridization (ISH) techniques have been
      used for the detection of lymphocystis disease virus (LCDV) in formalin-fixed,
      paraffin-embedded tissues from gilt-head seabream, Sparus aurata L. Diseased and
      recovered fish from the same population were analysed. IHC was performed with a
      polyclonal antibody against a 60-kDa viral protein. A specific digoxigenin
      labelled probe, obtained by PCR amplification of a 270-bp fragment of the gene
      coding the LCDV major capsid protein, was used for ISH. LCDV was detected in skin
      dermis and gill lamellae, as well as in several internal organs such as the
      intestine, liver, spleen and kidney using both techniques. Fibroblasts,
      hepatocytes and macrophages seem to be target cells for virus replication. The
      presence of lymphocystis cells in the dermis of the skin and caudal fin, and
      necrotic changes in the epithelium of proximal renal tubules were the only
      histological alterations observed in fish showing signs of the disease.

PMID- 18803583
TI  - Description and phylogeny of Ceratomyxa anko sp. n. and Zschokkella lophii sp. n.
      from the Japanese anglerfish, Lophius litulon (Jordan).
AB  - Two new species of myxozoans from the Japanese anglerfish, Lophius litulon, are
      described using myxospore morphology and small subunit rDNA sequences. Ceratomyxa
      anko sp. n. is a parasite of the gall bladder and had a prevalence of 57%. Mature
      spores of C. anko sp. n. are arcuate to crescent shaped with valves tapering to
      rounded tips. A prominent sutural line runs centrally between the round adjacent
      polar capsules containing the polar filament coiled two to three times. Spore
      measurements: length 10.8 (9.7-11.9) microm, width 41.9 (36.9-47.2) microm, polar
      capsule diameter 4.6 (4.1-5.3) microm. Ceratomyxa anko sp. n. can be
      distinguished from other Ceratomyxa spp. due to its spore dimensions and shape.
      Zschokkella lophii sp. n. is a parasite of the urinary bladder and had a
      prevalence of 70%. Mature spores are ellipsoidal to semicircular with bluntly
      pointed ends. The sutural line is curved or sinuous and the valves have no
      discernable surface ornamentation. Two almost spherical polar capsules are
      located separately in the ends of the spore, opening in almost opposite
      directions and contain the polar filament with five coils. Spore measurements:
      length 20.1 (16.8-24.0) microm, width 14.9 (12.7-16.8) microm, polar capsule
      diameter 5.1 (3.6-5.8) microm. Zschokkella lophii sp. n. can be distinguished
      from other Zschokkella spp. due to the terminal opening of the polar capsules
      within the spores and the site of infection within the host fish. In the
      phylogenetic analyses, C. anko sp. n. grouped with other members of the same
      genus forming a monophyly. Zschokkella lophii sp. n. forms a discrete clade with
      another Zschokkella sp. that infects the urinary bladder of marine fish. This
      grouping forms a sister clade to one containing members of the genus
      Parvicapsula, all of which are parasites of the urinary system in marine fish.

PMID- 18803584
TI  - The effects of water velocity on the Ceratomyxa shasta infectious cycle.
AB  - Ceratomyxa shasta is a myxozoan parasite identified as a contributor to salmon
      mortality in the Klamath River, USA. The parasite has a complex life cycle
      involving a freshwater polychaete, Manayunkia speciosa and a salmonid. As part of
      ongoing research on how environmental parameters influence parasite establishment
      and replication, we designed a laboratory experiment to examine the effect of
      water flow (velocity) on completion of the C. shasta infectious cycle. The
      experiment tested the effect of two water velocities, 0.05 and 0.01 m s(-1), on
      survival and infection of M. speciosa as well as transmission to susceptible
      rainbow trout and comparatively resistant Klamath River Chinook salmon. The
      faster water velocity facilitated the greatest polychaete densities, but the
      lowest polychaete infection prevalence. Rainbow trout became infected in all
      treatments, but at the slower velocity had a shorter mean day to death,
      indicating a higher infectious dose. Infection was not detected in Chinook salmon
      even at a dose estimated to be as high as 80,000 actinospores per fish. The
      higher water velocity resulted in lower C. shasta infection prevalence in M.
      speciosa and decreased infection severity in fish. Another outcome of our
      experiment is the description of a system for maintaining and infecting M.
      speciosa in the laboratory.

PMID- 18803587
TI  - Serum creatinine and bilirubin predict renal failure and mortality in patients
      with spontaneous bacterial peritonitis: a retrospective study.
AB  - BACKGROUND: Patients with spontaneous bacterial peritonitis (SBP) are at a high
      risk for renal failure and death despite successful treatment of infection.
      Intravenous (IV) albumin administration combined with antibiotic treatment has
      been shown to significantly decrease these risks. Clinical evidence is lacking on
      which patients are appropriate candidates for albumin treatment. AIM: To
      retrospectively analyse the usefulness of serum creatinine and bilirubin levels
      in predicting renal failure and mortality of patients hospitalized for SBP.
      METHODS: Between March 1995 and September 1998, 127 cirrhotic patients with SBP
      who had not received plasma expansion were evaluated. Eighty-one patients (64%)
      were classified as having a high risk for renal failure and mortality (serum
      bilirubin >4 mg/dl or serum creatinine >1 mg/dl) and 46 (36%) as having a low
      risk. RESULTS: At admission, 36.3% of all patients presented renal failure.
      Mortality during their hospitalization was 23% among those with a high risk and
      6.5% among those with a low risk (P=0.01). Renal failure occurred in 23% of the
      high-risk patients, compared with 2.6% of the low-risk patients (P=0.006). The
      presence of hyponatraemia was significantly associated with higher mortality and
      renal failure in the high-risk group. CONCLUSIONS: Our retrospective review of
      patients with SBP suggests that serum bilirubin levels >4 mg and serum creatinine
      levels >1 mg/dl at the time of diagnosis represent significant risk factors for
      the clinical outcomes of patients with SBP. Patients without these risk factors
      may have a very low likelihood of death or renal failure.

PMID- 18803588
TI  - Ultrasound-guided treatments under low acoustic power contrast harmonic imaging
      for hepatocellular carcinomas undetected by B-mode ultrasonography.
AB  - BACKGROUND/AIMS: The aim was to examine the efficacy of contrast-enhanced
      ultrasound (US) with Sonazoid to demonstrate ultrasonically unrecognizable
      hypervascular hepatocellular carcinoma (HCC) and apply percutaneous US-guided
      treatments. METHODS: The subjects of this prospective study were 44 cirrhotic
      patients with 55 hypervascular lesions (12.7+/-4.5 mm) found by contrast-enhanced
      computed tomography but unrecognized by non-contrast US. Contrast-enhanced US was
      performed to demonstrate these hepatic lesions after an intravenous injection of
      Sonazoid (0.0075 ml/kg). The sonograms in both the early phase (for 1 min after
      injection) and the late phase (5-10 min after) were taken in the harmonic imaging
      mode under a low mechanical index (0.24-0.3). RESULTS: Fifty-three lesions were
      demonstrated by contrast-enhanced US, 52 with positive enhancement in the early
      phase and 44 with negative enhancement in the late phase. Percutaneous US-guided
      treatments were successfully performed for 42 lesions (ethanol injection in 20
      and radiofrequency ablation in 22) in 32 patients with reference to contrast
      enhanced US findings. Six patients were treated by transarterial
      chemoembolization alone because they had more than three lesions in the liver. In
      the remaining seven lesions in six patients, six were diagnosed as non-HCC
      lesions: five with vascular abnormalities such as arterioportal or arteriovenous
      communication and the other one with benign lesion in alcoholic liver disease.
      These six lesions and one HCC lesion with severe liver damage were followed up
      without any treatment. CONCLUSIONS: As the detectability of ultrasonically
      unrecognizable hypervascular HCC improved by contrast-enhanced US with Sonazoid,
      a wider application of percutaneous US-guided treatments may be possible.

PMID- 18803589
TI  - Gene expression profile of Huh-7 cells expressing hepatitis C virus genotype 1b
      or 3a core proteins.
AB  - BACKGROUND: The liver disease expression in chronic hepatitis C patients is
      variable and may partially depend on the sequence of the infecting viral
      genotype. AIM: To identify some hepatitis C virus (HCV) genotype-specific virus
      host interactions potentially leading to clinically significant consequences.
      METHODS: We compared the gene expression profile of Huh-7 cells transiently
      expressing the core protein of HCV genotype 1b and 3a using microarray
      technology. RESULTS: Thirty-two genes were overexpressed in Huh-7 transfected
      with the HCV genotype 1b core protein and 57 genes in cells transfected with the
      genotype 3a core protein. On the other hand, we found 20 genes downregulated by
      core 1b and 31 genes by core 3a. These included genes involved in lipid transport
      and metabolism, cell cycle, immune response and insulin signalling. CONCLUSION:
      The expression of HCV core proteins of different genotypes leads to a specific
      gene expression profile. This may account for the variable disease expression
      associated with HCV infection.

PMID- 18803590
TI  - Over-expression of glutamine synthetase in focal nodular hyperplasia: a novel
      easy diagnostic tool in surgical pathology.
AB  - BACKGROUND AND AIMS: Glutamine synthetase (GS) is a useful marker in tumour liver
      pathology, including hepatocellular adenomas and nodules in cirrhosis. We
      investigated the use of GS as a marker in various clinical situations, in which
      FNH diagnosis had been firmly established to determine its contribution to
      diagnosis. METHODS: Seventy-nine cases of resected FNH, all on normal (or
      occasionally steatotic) livers, were retrieved from our collection. The control
      group was composed of hepatocellular adenomas and well-differentiated
      hepatocellular carcinoma. The following stains: H&E, Masson's trichrome, Gordon
      Sweet, PAS, perls and immunostains: CK7 and 19, and GS were carried out. FNH was
      diagnosed based on traditional pathological techniques. In case of uncertainty,
      particularly with hepatocellular adenoma, additional immunostainings including
      liver fatty acid-binding protein, serum amyloid A and beta-catenin were
      performed. RESULTS: Glutamine synthetase immunostaining was similar in all FNH
      cases. Positive GS staining of hepatocytic cytoplasms formed large areas,
      anastomosed in a 'map-like' pattern, often surrounding hepatic veins, whereas GS
      was not expressed in hepatocytes close to fibrotic bands containing arteries and
      ductules. In comparison, hepatocellular adenoma staining was completely
      different, even in cases of fibrotic bands due to tumour remodelling related to
      necrosis or haemorrhage. In hepatocellular adenomas or well-differentiated
      hepatocellular carcinoma presenting beta-catenin mutation, GS was positive but
      with a completely different pattern that appeared diffuse and not 'map-like'.
      CONCLUSION: Regardless of the FNH size or steatotic content, GS produced a
      similar and characteristic pattern and consequently represents a good marker for
      easily identifying resected FNH from other hepatocellular nodules.

PMID- 18803591
TI  - Linking movement behaviour to dispersal and divergence in plethodontid
      salamanders.
AB  - To better understand the evolutionary and ecological effects of dispersal, there
      is growing emphasis on the need to integrate direct data on movement behaviour
      into landscape-scale analyses. However, little is known about the general link
      between movement behaviour and large-scale patterns of dispersal and gene flow.
      Likewise, although recent studies suggest that nonrandom, directionally biased
      movement and dispersal can promote evolutionary divergence, the generality of
      this mechanism is unknown. We test the hypothesis that directionally biased
      movement and dispersal by plethodontid salamanders interact with the topography
      of headwater areas to affect genetic and phenotypic divergence. Movements by
      Gyrinophilus porphyriticus and Eurycea bislineata show contrasting directional
      biases: upstream bias in G. porphyriticus and downstream bias in E. bislineata.
      Consistent with predictions of how these biases interact with slope to affect
      dispersal and gene flow, genetic distance increased with slope in G.
      porphyriticus and decreased with slope in E. bislineata over a standardized
      distance of 1 km along six headwater streams. In both species, phenotypic
      divergence in relative trunk length was positively related to genetic divergence.
      These results indicate that landscape-scale patterns of dispersal and gene flow
      are closely related to movement behaviour in G. porphyriticus and E. bislineata,
      and underscore the value of information on movement behaviour for predicting and
      interpreting patterns of dispersal and gene flow in complex landscapes. This
      study also provides new evidence that directionally biased movement and dispersal
      can be important sources of intra- and interspecific variation in population
      divergence, and highlights the value of explicit, a priori predictions in
      landscape genetic studies.

PMID- 18803592
TI  - Microsatellite data show evidence for male-biased dispersal in the Caribbean
      lizard Anolis roquet.
AB  - Dispersal is a key component of an organism's life history and differences in
      dispersal between sexes appear to be widespread in vertebrates. However, most
      predictions of sex-biased dispersal have been based on observations of social
      structure in birds and mammals and more data are needed on other taxa to test
      whether these predictions apply in other organisms. Caribbean anole lizards are
      important model organisms in various biological disciplines, including
      evolutionary biology. However, very little is known about their dispersal
      strategies despite the importance of dispersal for population structure and
      dynamics. Here we use nine microsatellite markers to assess signatures of sex
      biased dispersal on two spatial sampling scales in Anolis roquet, an anole
      endemic to the island of Martinique. Significantly higher gene diversity (H(S))
      and lower mean assignment value (mAIC) was found in males on the larger spatial
      sampling scale. Significant heterozygote deficit (F(IS)), lower population
      differentiation (F(ST)), mAIC and variance of assignment index (vAIC) was found
      in males on the smaller spatial scale. The observation of male biased dispersal
      conform with expectations based on the polygynous mating system of Anolis roquet,
      and contributes to an explanation of the contrasting patterns of genetic
      structure between maternal and biparental markers that have been reported
      previously in this, and other anoline, species.

PMID- 18803593
TI  - Origin of the parasites of an invading species, the Australian cane toad (Bufo
      marinus): are the lungworms Australian or American?
AB  - Phylogeographical analyses that identify the geographical origin of parasites in
      invading species can clarify the parasites' potential for biological control of
      the invader and the risks posed by the parasite to native species. Our data on
      nuclear and mitochondrial genetic sequences show that the nematode lungworms
      (Rhabdias spp.) in invasive Australian populations of cane toads (Bufo marinus)
      are Rhabdias pseudosphaerocephala, a South American species. We did not find this
      lungworm species in any Australian frogs sympatric with cane toads, suggesting
      that the parasite does not attack Australian frogs and hence may offer potential
      as a biocontrol agent of the toad.

PMID- 18803594
TI  - Clonal population structure of the chestnut blight fungus in expanding ranges in
      southeastern Europe.
AB  - Expanding populations are often less genetically diverse at their margins than at
      the centre of a species' range. Established, older populations of the chestnut
      blight fungus, Cryphonectria parasitica, are more variable for vegetative
      compatibility (vc) types than in expanding populations in southeastern Europe
      where C. parasitica has colonized relatively recently. To test whether vc types
      represent clones, we genotyped 373 isolates of C. parasitica from southern Italy,
      Romania, Bulgaria, Macedonia, Greece and Turkey using 11 sequence-characterized
      amplified region (SCAR) markers. Ten SCAR loci and six vegetative incompatibility
      (vic) loci were polymorphic in these samples. These populations are clonal by all
      criteria tested: (i) among 373 isolates, we found only eight multilocus
      haplotypes, and the same haplotypes were found in multiple countries, sometimes
      separated in time by as much as 12 years; (ii) the number of haplotypes observed
      was significantly less than expected under random mating; (iii) populations are
      in linkage disequilibrium; (iv) the two sets of independent markers, SCARs and vc
      types, are highly correlated; and (v) sexual structures of C. parasitica were
      found only in Bulgaria and Romania. One mating type (MAT-1) was found in 98% of
      the isolates sampled. In contrast, a population in northern Italy, in the central
      part of the range in Europe, had 12 multilocus haplotypes among 19 isolates. The
      spread of a few clones could be the result either of founder effect and
      restricted migration, or these clones have greater fitness than others and spread
      because they are better adapted to conditions in southeastern Europe.

PMID- 18803595
TI  - Low levels of relatedness on black grouse leks despite male philopatry.
AB  - In lekking species, males cluster on specific areas for display (the leks) and
      females generally prefer to copulate with males on large aggregations. The
      maintenance of leks in which only a few males reproduce might be explained if
      subordinate males gain indirect fitness benefits. By joining a lek on which
      relatives are displaying, subordinates might attract more females to the lek
      thereby increasing the mating opportunities of their kin. In black grouse, a
      genetic structure among leks has previously been found suggesting that relatives
      could display together. Using 11 microsatellite loci, we extended this result by
      testing for the presence of kin structures in nine black grouse leks (101 males).
      The genetic differentiation among flocks was higher in males than in females,
      suggesting female-biased dispersal and male philopatry. Because of this genetic
      structure, males were more related within than among leks. However, the mean
      relatedness within each lek hardly differed from zero. The lekking males were not
      more related than random assortments of males from the winter flocks and there
      were no kin clusters within leks. Thus, black grouse males do not choose to
      display with and close to relatives. Male philopatry alone was not sufficient to
      induce elevated levels of relatedness on the leks either because of male partial
      dispersal or a rapid turnover of the successful males. The indirect fitness
      benefits associated with males' settlement decision are probably limited compared
      to the direct benefits of joining large aggregations such as increased current
      and future mating opportunities.

PMID- 18803596
TI  - Rapid adaptation of phytoplankters to geothermal waters is achieved by single
      mutations: were extreme environments 'Noah's Arks' for photosynthesizers during
      the Neoproterozoic 'snowball Earth'?
AB  - Geothermal waters often support remarkable communities of microalgae and
      cyanobacteria apparently living at the extreme limits of their tolerance. Little
      is known about the mechanisms allowing adaptation of mesophilic phytoplankters to
      such extreme conditions, but recent studies are challenging many preconceived
      notions about this. The aim of this study was to analyse mechanisms allowing
      adaptation of mesophilic microalgae and cyanobacteria to stressful geothermal
      waters. To distinguish between the pre-selective or post-selective origin of
      adaptation processes allowing the proliferation of mesophilic phytoplankters in
      geothermal waters, several Luria-Delbruck fluctuation analysis were performed
      with the microalga Dictyosphaerium chlorelloides and the cyanobacterium
      Microcystis aeruginosa, both isolated from nonextreme waters. Geothermal waters
      from seven places in Italy and five icebound places at Los Andes in Argentina
      were used as selective agents. Physiological adaptation was achieved in the least
      toxic waters. In contrast, rapid genetic adaptation was observed in waters
      ostensibly lethal for the experimental organisms. This adaptation was achieved as
      consequence of single mutations at one locus. It was hypothesized that a similar
      mechanism of rapid genetic adaptation could explain the survival of
      photosynthetic life during the Neoproterozoic 'snowball Earth,' where geothermal
      refuges such as those studied could have been 'Noah's Arks' for microalgae and
      cyanobacteria.

PMID- 18803598
TI  - Event-related potentials to auditory stimuli in monozygotic twins discordant for
      combat: association with PTSD.
AB  - Studies have demonstrated ERP abnormalities related to concentration difficulties
      in post-traumatic stress disorder (PTSD). We used an identical-twin, case-control
      design to investigate whether these abnormalities reflect pre-trauma
      vulnerability or the acquired consequence of PTSD. Vietnam combat veterans and
      their non-combat-exposed, identical twins completed a three-tone oddball task.
      Veterans with PTSD had delayed target N2 latencies compared to veterans without
      PTSD. In a small nonmedicated, nonsmoking subsample, veterans with PTSD also had
      significantly diminished target P3b amplitudes. A mixed-model, random-effects
      analysis on the nonmedicated, nonsmoking subsample that included the combat
      unexposed co-twins showed a significant Diagnosis x Combat Exposure interaction
      for target P3b amplitude. Results replicate increased N2 latency and diminished
      P3b amplitude in PTSD and suggest that diminished P3b amplitude is an acquired
      condition in PTSD.

PMID- 18803599
TI  - The error-related negativity is related to risk taking and empathy in young men.
AB  - We related self-report measures of risk taking and empathy to the error-related
      negativity (ERN) elicited during a flanker task in boys in late adolescence. We
      found that risk propensity (risk taking, sensation seeking, and sensitivity to
      reward) and empathy related to ERN amplitude (negatively and positively,
      respectively) but not to each other or to behavioral measures of response time,
      accuracy, and post-error slowing. They accounted for separate sources of variance
      in the ERN amplitude, suggesting that there are multiple routes to activation of
      its generator in the anterior cingulate. Impulsivity and sensitivity to
      punishment were unrelated to the ERN. The present study provides support that
      risk-taking traits and empathy affect anterior cingulate responsiveness to
      errors, and the ERN reflects the influence of the extent of individuals' concern
      with the outcome of events.

PMID- 18803600
TI  - Delta EEG activity as a marker of dysfunctional linguistic processing in
      developmental dyslexia.
AB  - The present study used delta EEG band to test the hypothesis of a cerebral
      maturational delay and a functional altered cerebral asymmetry for phonological
      processing in dyslexic children. A group of 14 children with dyslexia and 28
      matched controls participated in a linguistic paradigm in which the same words
      were processed in three tasks: phonological, semantic, and orthographic. Delta
      amplitude was computed as an index of cortical inhibition in four different
      phases of word processing. In anterior sites, controls showed left activation
      (reduced delta) during the phonological task and bilateral activation in the
      other two tasks. Conversely, children with dyslexia showed greater overall delta
      amplitude, indexing a cerebral maturation delay and an altered language
      laterality pattern. In the phonological task they had larger left anterior delta
      (inhibition of left frontal linguistic locations) and smaller left posterior
      delta amplitude (activation of left posterior sites silent in controls). Results
      support the phonological deficit hypothesis of developmental dyslexia and the
      validity of EEG delta band as functional and clinical measure of language
      laterality.

PMID- 18803601
TI  - Neural mechanisms underlying the processing of Chinese and English words in a
      word generation task: an event-related potential study.
AB  - Event-related brain potentials (ERPs) were used to examine the spatiotemporal
      cortical activation patterns underlying Chinese and English word generation
      (forming a new word by adding a stroke or a letter to an old Chinese or English
      word) for low- and high-proficiency Chinese-English bilinguals. The results
      revealed that early visual perceptual processing and word identification were
      similar between the two languages for the N120 and P220 waveforms. However, a
      greater negative potential (N250-350) was associated with Chinese words than with
      English words between 250 and 350 ms. Subsequently, for fluent Chinese
      bilinguals, Chinese words elicited a more positive ERP deflection (LPC) than did
      English words between 350 and 800 ms. The differences in ERP components between
      Chinese and English words indicates that there might be a real difference in the
      processing demands between these languages, and that the processing of English
      might be affected by the proficiency of the second language.

PMID- 18803602
TI  - Development of professional knowledge in action: experiences from an action
      science design focusing on acknowledging communication in mental health.
AB  - This article reports a multi-professional development project that was based on
      an action science design. The purpose was to develop 'acknowledging
      communication' in a psychiatric department for young people, and the objective to
      study the staffs' experiences of participating in the project. The professional
      part of the project has its foundation in Schibbye's treatment theory of inter
      subjective understanding of relationships, and involves three main approaches
      from her theory: self-reflection, self-delimitation and emotional presence. The
      article presents the specific action design used, where reflection processes were
      developed in three different arenas: multidisciplinary Reflection groups, a
      Leader support group for the group leaders of the Reflection groups and
      collective Project seminars for all employees. A formal study programme designed
      to increase professional expertise, 15 European Credit Transfer System (ECTS),
      was also offered. The research methods included the researcher's process notes
      taken during the process, field notes from participating in the Leader support
      group, and qualitative interviews of eight informants participating in the
      various reflection arenas. The article presents and discusses the experiences
      evolved from the methods that were developed during the professional action
      science project: reflection on specific situations of interaction with patients
      in the form of oral/written narratives and the development of video presentations
      in combination with 'reflective teams'. The study showed that to facilitate
      change in the role of staff members, it is important to combine several
      reflection arenas where theoretical principles can be converted into practical
      action. By drawing data from only one study site, the study has a limited
      transferability, but should be of interest for professionals working with
      clinical change processes.

PMID- 18803603
TI  - The incomprehensible injury--interpretations of patients' narratives concerning
      experiences with an acute and dramatic spinal cord injury.
AB  - Spinal cord injury is one of the most devastating incidents that can occur to an
      individual as it results in life being suddenly, dramatically, radically and long
      lastingly changed. Different studies show that a spinal cord injury is a
      stressful event, leading to physiological dependence, psychological and social
      illness and suffering, although the situation tends to improve over time. This
      study is a part of a larger longitudinal study. The aim of this study was to
      explore and interpret 10 individuals' experiences in connection with their acute
      and unexpected spinal cord injury. This qualitative study has a descriptive and
      explorative design and is a part of a larger study. A phenomenological
      hermeneutic approach inspired by Ricoeur was used to extract the meaningful
      content of the patients' narratives. In this study, the findings revealed three
      main themes: (I) 'the incomprehensible shock', (II) 'brave survivors' and (III)
      'miracles, luck or coincidences?' The incomprehensible spinal cord injury was
      often experienced as a dramatic and unexpected shock in the middle of a pleasant
      occasion, and every participant felt immediately overwhelmed by emotional
      suffering, such as despair and panic, but also anxiety, confusion, sorrow, guilt,
      shame, fear, aggression or depression at the moment of injury. Some individuals
      immediately understood that they had become completely paralysed and that
      something was seriously wrong with their body. Many also experienced guilt or
      shame because of choices or decisions made immediately before the injury. Several
      of the narratives were illuminating participants that had been brave survivors
      and heroes and saved others (passengers or friends) during the injury, by
      preventing the car form driving out or by softening the fall of co-passengers,
      which also entailed more serious injuries to themselves. However, the fact of
      having survived was experienced as 'being lucky, after all'. They all repeatedly
      reflected on the accident, and their individual understanding of it changed over
      time, from, on the whole, as a perspective of a 'miracle' to 'just luck' or a
      coincidence' which also reflected the meaning and significance of what the injury
      really meant to their body and to their lives. And these reflections gave rise to
      different ways; they later on learned to live with their new lives. These
      important aspects, narrated by the brave survivors, have not been reported in the
      research literature earlier.

PMID- 18803604
TI  - The dynamics of the nurse-patient relationship: introduction of a synthesized
      theory from the patient's perspective.
AB  - The nurse-patient relationship is by many considered the core of nursing. In this
      paper, a synthesized theory on the dynamics of that relationship is introduced
      from the patient's perspective. It is described as a dynamic lived reality
      characterized by a sense of spiritual connection which is experienced as a bond
      of energy. The highest quality of this connection is the life-giving nurse
      patient relationship which is greatly empowering for the patient. The
      prerequisites for the development of the nurse-patient relationship are perceived
      nurse caring, wisdom and competence in connecting with people. The dialectic
      nature of this relationship is discussed as well as the six main phases in the
      nurse-patient relationship development.

PMID- 18803605
TI  - Monocyte exposure to Saccharomyces cerevisiae cell wall mannan and decreased TNF
      alpha production in mild asthma: a role for mannan-binding lectin?
AB  - A correlation between fungal exposure and aggravation of inflammatory symptoms in
      asthmatic individuals is well documented in the literature. However, the
      molecular mediators responsible for clinical symptoms due to fungal exposure in
      individuals with asthma are still not known. The fungal cell wall polysaccharide
      mannan stimulates production of pro-inflammatory cytokines such as tumour
      necrosis factor (TNF)-alpha in monocytes. Recently, a role for the plasma protein
      mannan-binding lectin (MBL) has been proposed in individuals with severe
      asthmatic disease, although little is known about its role in those with mild and
      untreated asthma. MBL has been reported to modulate inflammatory cytokine
      production, but the mechanisms are not known. We conducted a pilot study and
      found that the cell wall mannan preparation used stimulated lower TNF-alpha
      production by monocytes from asthmatic subjects compared with that from healthy
      subjects in the presence of autologous plasma. Lipopolysaccharide-induced TNF
      alpha production was not significantly different between the groups. Further,
      plasma MBL levels in individuals with mild asthma were slightly increased
      compared with those in normal subjects, although the difference was not
      statistically significant. We speculate that reduced TNF-alpha production in
      monocytes from asthmatic subjects after fungal cell wall mannan stimulation could
      partly be influenced by plasma components such as MBL.

PMID- 18803606
TI  - Prophylactic efficacy of high-molecular-weight antigenic fractions of a recent
      clinical isolate of Leishmania donovani against visceral leishmaniasis.
AB  - T-cell mediated immune responses are key determinants to the natural course of
      infection caused by intracellular parasites such as Leishmania. Thus, T-cell
      activating proteins of these microbes continue to generate active interest
      particularly in view of their possible role in the design and development of
      newer and more effective vaccines. We have recently reported the presence of T
      cell immunostimulatory antigens with the high-molecular-weight (MW) fractions
      (134-64.2 kDa) of whole Leishmania donovani antigen (strain 2001), which
      stimulated variable amounts of IFN-gamma, IL-12 and IL-10 in exposed immune
      individuals. The present study was undertaken to further evaluate these high-MW
      antigenic fractions (MW range >100-60 kDa) for potential protective efficacy. The
      high-MW region of the parasite was resolved into five antigenic fractions (Prep A
      E) using continuous elution gel electrophoresis. Prior to in vivo protection
      studies in hamsters, these fractions were used to evaluate in vitro cellular
      responses in eight Leishmania-exposed individuals and treated cured hamsters. The
      protective efficacy of prep (A + B), C, D and E in combination with BCG was
      evaluated in inbred hamsters using standard immunization protocol. Proliferative
      responses were seen in all eight of eight exposed individuals to prep D [median
      stimulation index (SI): 5.2 (range 3.9-7.1)] and E [median SI: 5.6 (range 4.4
      8.2)], five of eight individuals to prep B and prep C and three of eight to prep
      A [median SI: 0.2 (range 0.1-7.2)]. The median proliferative responses to prep D
      and prep E were significantly higher than to fraction prep A; (P < 0.05) but not
      to prep B and prep C. However, prep A-E induced equivalent levels of IFN-gamma,
      IL-10 and IL-12 cytokines. Fractions D and E also exhibited marked parasite
      inhibition in spleen (52.5% and 73.7%) and liver (65% and 80.2%) as compared with
      prep (A + B) (23% in spleen and 24% in liver) and prep C (38% in spleen and 24%
      in liver). Prep D and prep E vaccinated animals showed higher in vitro
      stimulatory responses (mean SI: 6.6 and 8.8) and nitric oxide (NO) induction
      (mean NO levels: 6.4 and 10.7 mug/ml) against whole cell extract as compared with
      other groups. The protection also correlated with presence of suppressed
      Leishmania-specific IgG levels in prep D and prep E immunized hamsters. These
      studies indicate the presence of immunostimulatory and protective molecules in 60
      80 kDa region of L. donovani, which may be further exploited for developing a
      subunit vaccine.

PMID- 18803607
TI  - Strategy to assess the overall cytokine profile of circulating leukocytes and its
      association with distinct clinical forms of human Chagas disease.
AB  - Herein we have employed an alternative strategy to assess the cytokine patterns
      of circulating leukocytes and correlate dominant cytokine profiles with
      indeterminate-IND and cardiac-CARD clinical forms of Chagas disease. We have
      first calculated median percentages of cytokine-positive leukocytes of our study
      sample to establish, for each cytokine-positive cell population, the cut-off edge
      that would segregate 'low' and 'high' cytokine producers to build colour diagrams
      and draw a panoramic cytokine chart. Using this approach we demonstrated that
      most IND individuals presented a dominant regulatory cytokine profile, whereas
      CARD individuals displayed a dominant inflammatory cytokine pattern. In addition,
      radar chart analysis confirmed the dichotomic cytokine balance between IND and
      CARD groups and further allowed the identification of the relative contribution
      of each cell population for the global cytokine pattern. Data analysis
      demonstrated that CD4+ T cells were the major cell population defining the
      regulatory profile in IND, whereas monocytes and CD4+ T cells determined the
      inflammatory cytokine pattern in CARD individuals. Interestingly, in vitro
      stimulation with trypomastigote Trypanosoma cruzi antigen was able to invert the
      cytokine balances in IND and CARD groups. Upon antigenic stimulation, changes in
      the frequencies of IL-10-producing CD4+ T cells and monocytes drove IND
      individuals towards an inflammatory pattern and CARD towards a regulatory
      cytokine profile. A similar inversion could be found after in vivo treatment of
      IND and CARD individuals with benzonidazole. Altogether, these findings shed some
      light into the complex cytokine network underlying the immunopathogenesis of
      Chagas disease and provide putative immunological biomarkers of disease severity
      and therapeutic response.

PMID- 18803608
TI  - The monoclonal antibody 6B9 recognizes CD44 and not cell surface transglutaminase
      2.
AB  - The multifunctional enzyme transglutaminase 2 (TG2) can be located
      intracellularly, in the extracellular matrix (ECM) and on the cell surface. Cell
      surface TG2 (csTG2) is poorly recognized both by most TG2-specific commercial
      antibodies and celiac disease-associated anti-TG2 autoantibodies. The recent
      characterization of a csTG2-specific monoclonal antibody (mAb), which did not
      recognize ECM-associated TG2, suggested major conformational differences between
      csTG2 and TG2 found in the ECM. Subsequent findings based on this antibody
      indicated ubiquitous abundance and novel roles of csTG2 in innate immune
      responses. We wished to identify the epitope of 6B9 so as to shed light on the
      disparate antibody binding properties of csTG2- and ECM-associated TG2.
      Surprisingly, and despite thorough effort, we were unable to isolate TG2 as the
      antigen of 6B9. We found that 6B9 does not react with recombinant human TG2. In
      immunoprecipitation experiments, 6B9 pulled down an 85 kDa protein which was
      identified as CD44 by mass spectrometry. Several flow cytometry experiments
      including the testing of CD44s transfectants indicated that CD44, and not csTG2,
      is the antigen of 6B9. We conclude that 6B9 does not recognize csTG2 but rather
      the cell surface glycoprotein CD44. Thus, recent knowledge of csTG2 gained
      through the use of 6B9 should be reevaluated.

PMID- 18803609
TI  - Mucosal administration of completely non-replicative vaccinia virus recombinant
      Dairen I strain elicits effective mucosal and systemic immunity.
AB  - We studied the immunogenicity of completely replication-deficient vaccinia virus
      Dairen I strain recombinant encoding simian immunodeficiency virus (SIV) gag/pol
      (rDIs) in both mucosal and systemic compartments. When administered either
      intranasally or intragastrically, rDIs elicited enhanced levels of both SIV Gag
      p27-specific IgA antibodies and specific plasma antibodies, and the enhanced
      immunity persisted for the 1-year of observation by intranasal immunization.
      Increases were observed in antigen-specific IgA antibody-forming cells (AFC) in
      intestinal mucosal tissues and in IgG AFC in spleens. Furthermore, induction of
      type 1 and 2 helper cytokines in CD4+ spleen T cells and of CD8+ IFN-gamma spot
      forming cells in mucosal tissues was observed in the intranasally immunized mice.
      Moreover, not even high-dose rDIs generated an SIV gene signal in the brain
      tissues of immunized mice. These findings suggest that mucosal immunization with
      the DIs recombinant hold promise as a safe mucosal vector.

PMID- 18803610
TI  - Analysis of circulating populations of Plasmodium falciparum in mild and severe
      malaria in two different epidemiological patterns in Madagascar.
AB  - OBJECTIVE: To investigate whether the severity of Plasmodium falciparum attack in
      endemic areas was associated with the multiplicity of infection (MOI) and/or with
      a particular genotype(s). METHOD: In two areas of different malaria transmission
      pattern in Madagascar (Sainte-Marie - mesoendemic and Tsiroanomandidy -
      hypoendemic) the number and the proportions of msp-2 genotypes within isolates
      were determined for each patient using a capillary electrophoresis genotyping
      method. DNA sequencing was performed to identify the msp-2 allelic family of
      dominant clones. RESULTS: Eighty six uncomplicated and 33 severe cases were
      included in Sainte-Marie and 48 uncomplicated and 69 severe cases were included
      in Tsiroanomandidy. We found no association between the MOI and severity of
      malaria as the same mean number of msp-2 genotypes was found in isolates from
      uncomplicated and from severe malaria cases (3.72 and 3.73, respectively,
      P>0.05). The study of the association of dominant clones with clinical status
      showed no particular genotype or allelic family associated with malaria severity.
      CONCLUSIONS: Severity of malaria was not associated with higher MOI in our study.
      Severity did not appear restricted to some particular genotypes either. On the
      contrary, severe malaria appeared to be caused by very common genotypes in the
      studied areas. More comprehensive explorations including immunity and genetic
      factors of the host are needed to acquire new information about this complex
      condition.

PMID- 18803611
TI  - Diagnostic accuracy of a new Leishmania PCR for clinical visceral leishmaniasis
      in Nepal and its role in diagnosis of disease.
AB  - OBJECTIVE: To develop a new PCR for Leishmania detection and to estimate its
      diagnostic accuracy in a visceral leishmaniasis (VL) endemic area. METHODS: After
      providing the proof-of-concept, the diagnostic accuracy was estimated on blood
      from 247 non-endemic control persons and on blood and bone marrow from 173
      confirmed VL, 39 probable VL and 87 non-VL patients from south-eastern Nepal.
      RESULTS: The PCR showed a specificity of 99.64% [95% confidence interval (CI):
      98.93-100%) on non-endemic controls and a sensitivity of 92.1% (95% CI: 87.6
      96.6%) on blood and 92.9% (95% CI: 89-96.8%) on bone marrow from the confirmed VL
      patients. Leishmania DNA was detected in blood and bone marrow of 67.6% (95% CI:
      50.8-80.9%) and 71.8% (95% CI: 56.2-83.5%) of the probable VL patients,
      respectively, and of 38.2% (95% CI: 28-49.4%) and 29.9% (95% CI: 21.3-40.2%) of
      the non-VL patients, respectively. The PCR showed 97% concordance with a positive
      DAT status while for a negative DAT status this was only 41.3% (kappa-index
      0.416, 95% CI: 0.30-0.53). CONCLUSIONS: Our findings indicate that PCR alone
      rather provides a marker for infection than a marker for disease and its role in
      VL diagnosis in endemic regions is discussed.

PMID- 18803612
TI  - Clinical and laboratory features that distinguish dengue from other febrile
      illnesses in endemic populations.
AB  - OBJECTIVE: Clinicians in resource-poor countries need to identify patients with
      dengue using readily-available data. The objective of this systematic review was
      to identify clinical and laboratory features that differentiate dengue fever (DF)
      and/or dengue haemorrhagic fever (DHF) from other febrile illnesses (OFI) in
      dengue-endemic populations. METHOD: Systematic review of the literature from 1990
      to 30 October 2007 including English publications comparing dengue and OFI.
      RESULTS: Among 49 studies reviewed, 34 did not meet our criteria for inclusion.
      Of the 15 studies included, 10 were prospective cohort studies and five were case
      control studies. Seven studies assessed all ages, four assessed children only,
      and four assessed adults only. Patients with dengue had significantly lower
      platelet, white blood cell (WBC) and neutrophil counts, and a higher frequency of
      petechiae than OFI patients. Higher frequencies of myalgia, rash, haemorrhagic
      signs, lethargy/prostration, and arthralgia/joint pain and higher haematocrits
      were reported in adult patients with dengue but not in children. Most
      multivariable models included platelet count, WBC, rash, and signs of liver
      damage; however, none had high statistical validity and none considered changes
      in clinical features over the course of illness. CONCLUSIONS: Several individual
      clinical and laboratory variables distinguish dengue from OFI; however, some
      variables may be dependent on age. No published multivariable model has been
      validated. Study design, populations, diagnostic criteria, and data collection
      methods differed widely across studies, and the majority of studies did not
      identify specific aetiologies of OFIs. More prospective studies are needed to
      construct a valid and generalizable algorithm to guide the differential diagnosis
      of dengue in endemic countries.

PMID- 18803613
TI  - Correlates of HIV testing among women in Malawi: results from the 2006 Multiple
      Indicator Cluster Survey.
AB  - We report a study of women 15-49 years aimed at assessing correlates of HIV
      testing and having received test results in a nationally representative survey of
      women in Malawi. A total of 26 259 women were recruited into the study, of whom
      3712 (14.1%) had ever been tested for HIV infection and received their results.
      We found that age and education were not significantly associated with HIV
      testing but marital status, wealth, region were. Contrary to our expectations
      that women who had delivered a child were more likely to have been ever tested
      when accessing prenatal and intra-partum care, we found that women who had
      delivered a child in the 2 years before the survey were less likely to have ever
      been tested. We suggest that by 2006 when the survey was conducted, prenatal and
      intra-partum care were not important avenues for HIV testing in Malawi.

PMID- 18803614
TI  - Using field-based epidemiological methods to investigate FMD outbreaks: an
      example from the 2002 outbreak in Korea.
AB  - Relevant to foot and mouth disease (FMD), most published epidemiological studies
      have been conducted using quantitative methods and substantial regional or
      national datasets. Veterinary epidemiology also plays a critical role during
      outbreak investigations, both to assist with herd-level decision-making and to
      contribute relevant information to assist with ongoing national or regional
      control strategies. Despite the importance of this role, however, little
      information has been published on the use of applied (field-based)
      epidemiological methods during disease outbreaks. In this study, we outline an
      investigative template for FMD, and a case study of its use during the 2002 FMD
      outbreak in Korea. Suitable for use during field-based epidemiological
      investigations of individual farms within a broader regional/national response,
      the template considers three steps including confirming infection, estimating
      date of introduction and determining method of introduction. A case study was
      conducted on IP13 (the 13th infected premises), the only IP during the 2002 FMD
      outbreak in Korea that was geographically isolated from all other known cases.
      The authorities first became aware of FMD on IP13 on 2 June, however, infection
      may have been present from 12 May. Infection was confirmed on 3 June 2002. FMD
      was probably spread to IP13 by a contract worker who had participated during 2-4
      May in the culling operations on IP1. Other routes of spread were ruled out
      during the investigation. The contract worker lived in the locality of IP13 and
      worked on a part-time basis at a pork-processing plant that was adjacent to this
      farm. The contractor became heavily contaminated during the cull, but did not
      comply fully with cleaning and disinfection requirements once the cull had been
      completed. The investigative template contributed structure and focus to the
      field-based investigation. Results from this case study demonstrate the need for
      strict management of personnel in disease control and adherence to the sanitary
      rules by all those involved.

PMID- 18803615
TI  - Acute effect of low-flux hemodialysis process on the results of the interferon
      gamma-based QuantiFERON-TB Gold In-Tube test in end-stage renal disease patients.
AB  - BACKGROUND: Screening for latent tuberculosis infection before solid organ
      transplantation is mandatory, but this is not so easy in uremic patients on
      hemodialysis (HD) treatment. The newly developed interferon-gamma (IFN-gamma)
      based QuantiFERON((R))-TB Gold In-Tube test (QFT-G) seems to be superior to the
      other available tests. Objective. To investigate the acute effect of the low-flux
      HD process on the results of the QFT-G assay. METHODS: A total of 56 HD patients
      participated in this prospective study. They were dialyzed under low-flux HD for
      at least 1 month before blood sampling for QFT-G assay. This assay was performed
      before and after the 4-h low-flux HD session. RESULTS: Compared with the pre
      dialysis level, there was an obvious reduction in the IFN-gamma production level
      (in response to the TB-antigen cocktails) after the HD process (P=0.00). The pre
      dialysis test result was negative in 21 (37.5%), positive in 33 (58.9%), and
      indeterminate in 2 (3.6%) patients. One pre-dialysis negative result changed to
      positive after the HD process. On the other hand, 7 pre-dialysis positive and 2
      indeterminate results become negative after HD (P=0.012). CONCLUSION: In order to
      maintain the sensitivity of QFT-G assay in chronic renal failure patients on low
      flux HD treatment, it is better to perform the test immediately before (not
      after) the HD process.

PMID- 18803616
TI  - Microsporidiosis in solid organ transplant recipients: two Enterocytozoon
      bieneusi cases and review.
AB  - Microsporidiosis first came to prominence as an opportunistic infection in
      patients with acquired immunodeficiency syndrome. Microsporidia are now emerging
      pathogens responsible for severe diarrhea during solid organ transplantation. Two
      main clinical entities can be identified: infection by Enterocytozoon bieneusi,
      causing diarrhea with limited treatment options; and infection by Encephalitozoon
      intestinalis, which may disseminate and usually responds to albendazole
      treatment. We describe here 2 cases of microsporidiosis caused by E. bieneusi in
      a renal and a liver transplant recipient, respectively, in whom complete clinical
      efficacy of a short course of fumagillin therapy was obtained. Long-term
      microbiological eradication was assessed using classical methods and monitored
      using a real-time quantitative polymerase chain reaction-based method. Both
      patients experienced drug-induced thrombocytopenia, which resolved after
      withdrawal of the treatment. We also review the 18 other previously reported
      cases of microsporidiosis in transplant recipients. In case of persistent
      diarrhea in solid organ transplant patients, microsporidiosis should be
      considered. Based on the present experience, treating E. bieneusi infection with
      7 days of fumagillin therapy is adequate to eradicate E. bieneusi in this
      context.

PMID- 18803617
TI  - Pneumocystis jirovecii pneumonia after rituximab therapy for antibody-mediated
      rejection in a renal transplant recipient.
AB  - We report the case of a 54-year-old woman who underwent living-related renal
      transplantation for end-stage renal disease from IgA nephropathy. She was
      subsequently diagnosed with antibody-mediated rejection (AMR) and received
      rituximab, a potent B-cell suppressive agent. After therapy with rituximab, she
      developed Pneumocystis jirovecii pneumonia (PJP) requiring hospitalization. We
      discuss the increasing literature for the use of rituximab for AMR and the need
      for PJP prophylaxis in this setting.

PMID- 18803618
TI  - Poor graft outcome in recipients with de novo donor-specific anti-HLA antibodies
      after living related kidney transplantation.
AB  - Antibody-mediated rejection (AMR) is now widely recognized as a major problem in
      organ transplantation. This study was conducted to investigate the relationship
      between newly developing anti-HLA antibodies post-transplantation (de novo Abs)
      and the outcome of living related kidney transplantation (LRKT). The subjects
      included 87 patients who had received living donor kidney allografts at our
      institution. Panel reactive Ab assay (Flow-PRA) and graft biopsies were performed
      in all the recipients before and 6 months after the LRKT. The incidence of AMR,
      the donor specificity and time of appearance of the de novo Abs were
      retrospectively studied. Among the 87 LRKT recipients, 47 (54%) showed
      negative/negative (N/N) results, 15 (17%) showed positive/positive (P/P) results,
      12 (14%) showed positive/negative results (P/N), and 13 (15%) showed
      negative/positive (N/P) results (de novo Abs) in the pre-/post-transplant Flow
      PRA analysis. Among the 13 cases with de novo Abs, 5 (38%) had donor-specific Abs
      (DSA) and the remaining 8 (62%) had nondonor-specific Abs, as determined by LAB
      single antigen analysis. Eighty percent of the recipients with DSA showed
      evidence of AMR in the graft biopsies. The 5-year graft survival rate of the
      recipients with de novo Abs (N/P) was 69%, as compared with 96% in the N/N, 88%
      in the P/N and 93% in the P/P recipient groups (P = 0.009). LRKT recipients
      developing de novo Abs, especially those with DSA, showed a much higher incidence
      of AMR and a worse prognosis. Cautious monitoring for the appearance of anti-HLA
      Abs should be adopted after transplantation, even in patients without anti-HLA
      Abs prior to the transplantation.

PMID- 18803619
TI  - Determination of threshold concentrations of multiple allergenic extracts for
      equine intradermal testing using normal horses in three seasons.
AB  - Forty-one normal horses were evaluated for reactivity to intradermally injected
      aqueous allergens to determine allergen threshold concentrations (TC), with
      potential relevance to equine intradermal testing (IDT). Horses were tested three
      times over 1 year to assess seasonal variation in reactivity, using three to five
      serial dilutions of 27 allergens each time. Injection sites were evaluated after
      15 min, 1 h, 4 h and 24 h. The highest allergen concentration at which < 10% of
      horses demonstrated positive reactivity (subjective score of > or = 2, scale of 0
      to 4) at 15 min was considered the TC. The TC was determined for nine pollens
      (2000 to > 6000 PNU mL(-1)), four moulds (4000 to > 6000 PNU mL(-1)), seven
      insects (ant, horse fly 125 PNU mL(-1); house fly, cockroach 250 PNU mL(-1); moth
      60 PNU mL(-1); mosquito 1000 PNU mL(-1); Culicoides nebeculosis 1 : 5000 w v(-1))
      and three of four storage mites (1 : 10,000 w v(-1)). The TC was not determined
      due to excessive reactivity at the lowest concentrations tested for dust mites
      (Dermatophagoides farinae [< 1 : 12,000 w v(-1)], D. pteronyssinus [< 1 : 30,000
      w v(-1)]), and Acarus siro (< 1 : 10,000 w v(-1)). Minor variation in the TC for
      specific allergens occurred in different seasons. Progressive sensitization with
      repeat testing occurred for grain mill dust mix. Positive reactivity at 1 h and 4
      h occurred in > 10% of horses for nine of 19 allergens (pollens, mosquito,
      storage mites) at their determined TC. Positive reactivity was rare at 24 h. This
      study in normal horses suggests that appropriate testing concentrations of
      allergens for equine IDT in atopic horses may be > or = 1000 PNU mL(-1) for
      pollens and moulds, 60 to 250 PNU mL(-1) for most insects and < 1 : 12,000 w v(
      1) for dust mites; and that reactions at 1-4 h may be insignificant.

PMID- 18803620
TI  - Carriage of Malassezia spp. yeasts in Cornish Rex, Devon Rex and Domestic short
      haired cats: a cross-sectional survey.
AB  - Carriage of Malassezia spp. yeasts in healthy Cornish Rex cats (CRC) was compared
      with that in Devon Rex (DRC) and Domestic short-haired (DSH) cats. Samples
      obtained from the left external ear canal, anus and claw fold of digit III of the
      left fore foot by swabbing, and the axilla and groin using contact plates, were
      incubated for yeasts on modified Dixon's agar at 32 degrees C for 7 days.
      Malassezia species were isolated from 90% of the DRC, but from only 39% of the
      CRC and 50% of the DSH cats. M. pachydermatis accounted for 121 of 141 Malassezia
      spp. isolates. Five CRC were colonized by M. pachydermatis alone, one CRC yielded
      only M. nana, and one cat yielded only M. slooffiae, whereas five CRC were
      colonized by both M. pachydermatis and M. nana and another yielded M.
      pachydermatis, M. slooffiae and M. nana. M. nana was primarily isolated from the
      ear canal, whereas M. slooffiae was most often isolated from the claw. Both the
      frequencies of isolation and the population sizes of M. pachydermatis at all
      sites sampled in the CRC were comparable to those of 10 healthy DSH cats.
      Populations of M. pachydermatis in the left axilla and left and right groin in
      the CRC were significantly lower when compared with counts in a group of 21
      healthy DRC, a breed with very similar coat characteristics but prone to
      seborrheic dermatitis caused by M. pachydermatis.

PMID- 18803621
TI  - Apoptosis and anti-apoptotic heat shock proteins in canine cutaneous infundibular
      keratinizing acanthomas and squamous cell carcinomas.
AB  - Cell stress and death are linked in the neoplastic process, and heat shock
      proteins appear to play an important role by inhibiting apoptotic pathways. The
      apoptotic rates in 9 canine infundibular keratinizing acanthomas (IKAs) and 17
      canine squamous cell carcinomas (SCCs) were correlated with the
      immunohistochemical expression of caspase-3 and the antiapoptotic heat shock
      proteins Hsp27, 72 and 73. Apoptosis was evaluated using the terminal
      deoxynucleotidyl transferase biotin-dUTP nick end labelling (TUNEL) method. The
      absence of a correlation between the TUNEL index and active-caspase-3 expression,
      a paucity of active-caspase-3-positive cells and Hsp72 over-expression were
      considered to be indicative of inhibition of apoptosis, and suggestive that
      inhibition of cell death plays a key role in oncogenesis and tumour growth of
      some canine skin neoplasms.

PMID- 18803622
TI  - Analysis of the clinical efficacy of intravitreal bevacizumab in the treatment of
      iris neovascularization caused by proliferative diabetic retinopathy.
AB  - PURPOSE:  To evaluate the therapeutic effect of intravitreal bevacizumab
      (Avastin) (IVB) in the treatment of iris neovascularization (INV) in
      proliferative diabetic retinopathy (PDR). METHODS: A retrospective analysis on
      data collected from 28 eyes of 22 patients with PDR was performed. The analysis
      included grading of INV, visual acuity (VA) and intraocular pressure (IOP) prior
      to and after IVB treatment. RESULTS: Significant regression was noted in 20 eyes
      (71.4%); six eyes (21.4%) showed partial regression; no change or worsening was
      observed in two eyes (7.2%). VA (measured with a Snellen acuity chart) improved
      in five eyes (17.9%) while the remaining 23 eyes (82.1%) had no improvement. In
      the 11 eyes with preoperative neovascular glaucoma, IOP decreased in 10 eyes
      (91%) and increased in one eye (9%) after treatment. CONCLUSION: IVB treatment of
      INV in PDR patients shows a promising short-term result. Further studies are
      needed to evaluate long-term results.

PMID- 18803623
TI  - Long-term biomechanical properties of rabbit sclera after collagen crosslinking
      using riboflavin and ultraviolet A (UVA).
AB  - PURPOSE: Scleral crosslinking by the photosensitizer riboflavin and ultraviolet A
      (UVA) has been shown to increase significantly the scleral biomechanical rigidity
      and might therefore become a possible sclera-based treatment modality for
      progressive myopia. In the present study, the long-term effect of the new
      crosslinking method on biomechanical properties was investigated in the rabbit
      sclera. METHODS: A 10 x 10 mm sector of the equatorial sclera of nine Chinchilla
      rabbit eyes was treated in vivo using a UVA double diode of 370 nm with a surface
      irradiance of 3 mW/cm(2) and application of 0.1% riboflavin-5-phosphate drops as
      photosensitizer for 30 min. Three days, 4 months and 8 months postoperatively,
      biomechanical stress-strain measurements of the treated scleral strips were
      performed and compared to contralateral control sclera using a microcomputer
      controlled biomaterial tester. In addition, routine histological controls were
      performed. RESULTS: Following the crosslinking treatment, Young's modulus was
      increased by 320% after 3 days, 277% after 4 months and 502% after 8 months, and
      ultimate stress by 341% after 3 days, 131% after 4 months and 213.8% after 8
      months versus the controls. The decrease in ultimate strain was between 24% and
      44.8%. On histology, no tissue damage was detected. CONCLUSION: Our new method of
      scleral collagen crosslinking proved very effective and constant over a time
      interval of up to 8 months in increasing the scleral biomechanical strength.
      Therefore, the new treatment might become an option for strengthening scleral
      tissue in progressive myopia and other conditions associated with weakened
      sclera. There were no side-effects on the retina or retinal pigment epithelium.
      The new crosslinking treatment could now be tested in a suitable myopia model
      (like the tree shrew) and finally in human eyes.

PMID- 18803624
TI  - Benign neonatal sleep myoclonus in newborn infants of opioid dependent mothers.
AB  - OBJECTIVE: The aim of our study was to evaluate the incidence, duration and risk
      factors for benign neonatal sleep myoclonus (BNSM) in infants with neonatal
      abstinence syndrome (NAS) treated with opioids or sedatives, compared with
      control infants. METHODS: This is a single centre observational case control
      study. Seventy-eight near term and term infants with neonatal opiate abstinence
      syndrome confirmed by meconium analysis were included. Exclusion criteria were
      cerebral malformation, intracranial haemorrhage and perinatal asphyxia. The
      babies were assessed eight hourly with a modified Finnegan score that included
      sleep myoclonus. Seventy-eight infants not exposed to opiates during pregnancy,
      hospitalized for at least 14 days and matched for gestational age were used as
      controls. RESULTS: The median gestational age was 38 (1)/(7) (95% CI: 35 (3)/(7)
      41 (2)/(7)) weeks, birth weight 2730 (95% CI: 1890-3600) g, umbilical artery pH
      7.25 (CI 7.10-7.37) and Apgar score at 5 minutes 9 (95% CI: 7-10). The control
      infants did not differ in these characteristics. Sleep myoclonus was diagnosed in
      52 (67%) of the infants with NAS and 2 (2.6%) of the controls (OR 26 [95% CI: 7
      223], p < 0.001). Myoclonus appeared as early as day 2 and as late as day 56 of
      life (median day 6) and lasted for 1 to 93 days (median 13 days). All infants had
      serum glucose > 2.5 mmol/L at first occurrence. The neurological examinations as
      well as cerebral ultrasound scans were normal. An electroencephalogram (EEG)
      carried out in 18 infants showed no signs of epileptic activity. CONCLUSION: BNSM
      has a high incidence in infants with NAS. The diagnosis can be made clinically.
      In the absence of other neurological symptoms further investigations such as EEG
      are not necessary and anticonvulsive treatment is not indicated.

PMID- 18803625
TI  - Comparison of thrombophilic gene mutations among patients experiencing recurrent
      miscarriage and deep vein thrombosis.
AB  - PROBLEM: Inherited thrombophilia has been shown to be a risk factor for
      cardiovascular disease including deep venous thrombosis as well as reproductive
      disorders including recurrent pregnancy loss. We have previously reported three
      out of the 10 thrombophilic mutations studied, plasminogen activator inhibitor-1
      (PAI-1) 4G/5G, factor XIII V34L, and homozygous MTHFR C667T, correlated
      significantly with recurrent pregnancy loss compared with controls. This study
      was undertaken to compare the frequencies of nine inherited thrombophilias among
      women with a history of recurrent pregnancy loss with individuals experiencing
      deep venous thrombosis and fertile controls. METHOD OF STUDY: Six hundred thirty
      four participants including 550 women with a history of recurrent pregnancy loss,
      43 individuals with deep vein thrombosis and 41 fertile women without a history
      of recurrent miscarriage. All participants had buccal swabs taken for DNA
      analyses of nine gene polymorphisms including factor V G1691A, factor V H1299R
      (R2), factor II Prothrombin G20210A, factor XIII V34L, beta-fibrinogen -455G>A,
      PAI-1 4G/5G, human platelet antigen 1 a/b (L33P), MTHFR C677T, MTHFR A1298C.
      Frequencies of thrombophilic gene polymorphisms were compared among the three
      populations studied. RESULTS: Individuals with a history of DVT had a
      significantly higher frequency of all of the polymorphisms studied compared with
      women experiencing a history of recurrent pregnancy loss and the fertile
      controls. The frequencies of mutations for V34L and PAI-1 4G/5G were
      significantly increased among women experiencing recurrent pregnancy loss
      compared with controls. The most prevalent polymorphisms were factor XIII V34L
      and PAI-1 4G/4G for both individuals with a history of deep vein thrombosis and
      recurrent pregnancy loss compared with controls. CONCLUSION: Screening for risk
      factors for inherited thrombophilia with only polymorphisms for factor V von
      Leiden, factor II prothrombin and MTHFR may be missing the more prevalent
      identifiers of jeopardy.

PMID- 18803626
TI  - Poly-immunoglobulin receptor-mediated transport of IgA into the male genital
      tract is important for clearance of Chlamydia muridarum infection.
AB  - PROBLEM: Chlamydia trachomatis is the most common sexually transmitted infection
      worldwide. While infection in females requires a Th1 response for clearance, such
      a response in males may disrupt the immune privileged nature of the male
      reproductive tract, potentially contributing to infertility. METHOD OF STUDY: We
      investigated the role of IgA in protection against an intrapenile Chlamydia
      muridarum infection of C57BL/6 and pIgR-/- mice. RESULTS: Here, we show that the
      poly immunoglobulin receptor is the main pathway for IgA transport into the male
      reproductive tract. The high levels of IgA seen in prostatic fluid of wild-type
      mice correlate with reduction in chlamydial infection both in vitro and in vivo.
      CONCLUSION: These findings indicate that a Chlamydia vaccine that induces
      neutralizing IgA in the prostate will aid in the protection against infection in
      males.

PMID- 18803627
TI  - Development of a risk stratification model for predicting acute renal failure in
      orthotopic liver transplantation recipients.
AB  - The purpose of this prospective observation cohort study was to develop and
      validate a risk stratification model for prediction of acute renal failure after
      liver transplantation. Data from 71 orthotopic liver transplantation recipients
      were used to develop a risk stratification model by binary logistic regression
      analysis containing the following variables: pretransplant hepatitis B and/or C
      infection; arterial hypertension; intra-operative mean arterial blood pressure
      before induction of anaesthesia; units of packed red blood cells required;
      hypotension (mean arterial blood pressure <or=50 mmHg); and maximum lactate
      concentration. Validation of the model on 167 consecutive patients revealed a
      sensitivity of 0.78, a specifity of 0.92, a negative predictive value of 0.96 and
      a positive predictive value of 0.62. This risk stratification model enables
      identification of orthotopic liver transplantation recipients with no or low risk
      for acute renal failure directly at the end of the transplantation procedure.

PMID- 18803628
TI  - Patient safety incidents associated with equipment in critical care: a review of
      reports to the UK National Patient Safety Agency.
AB  - We reviewed all patient safety incidents reported to the UK National Patient
      Safety Agency between August 2006 and February 2007 from intensive care or high
      dependency units. Incidents involving equipment were then categorised. A total of
      12 084 incidents were submitted from 151 organisations (median (range) 40 (1-634)
      per organisation). Of these, 1021 incidents were associated with use of
      equipment, most commonly involving syringe pumps/infusion devices (185
      incidents), ventilators (164 incidents), haemofilters (107 incidents) and
      monitoring equipment (70 incidents). Twenty-nine incidents were associated with
      more than temporary harm to patients. Failure or faulty equipment was described
      in 537 incidents (26% with some harm) and incorrect setting or use was described
      in 358 incidents; these were more likely to be associated with harm (39%; p =
      0.001). We suggest changes to improve the reporting of incidents and to improve
      equipment safety.

PMID- 18803629
TI  - High frequency jet ventilation through the laryngeal mask airway in a critically
      obstructed airway.
AB  - SUMMARY: A 72 year-old man with an anticipated difficult airway secondary to a
      large, obstructing supraglottic tumour was scheduled for a panendoscopy. An
      elective pre-induction transtracheal catheter was placed to allow oxygenation if
      airway maintenance proved difficult. Following induction of anaesthesia, tracheal
      intubation was impossible and ventilation via both a facepiece and a laryngeal
      mask airway became progressively more difficult. An emergency tracheostomy was
      attempted whilst oxygenation was maintained with transtracheal jet ventilation,
      but the position of the transtracheal catheter made tracheostomy impossible. The
      catheter was removed and high frequency jet ventilation was then used via the
      laryngeal mask airway to maintain oxygenation. To our knowledge, the use of high
      frequency jet ventilation through the laryngeal mask airway in a critically
      obstructed airway has not been described before.

PMID- 18803630
TI  - Expression of hepatocyte nuclear factor 4alpha in developing mice.
AB  - Hepatocyte nuclear factor (HNF) 4alpha, a transcription factor of the nuclear
      hormone receptor family, is generally expressed in some endoderm-derived
      epithelial tissues such as hepatocytes. In mice, an alternative promoter referred
      to as the P2 promoter is located upstream from the P1 promoter, resulting in the
      transcription of at least nine isoforms. In this study, we investigated the
      expression of Hnf4alpha in adult and embryonic mouse tissues, paying special
      attention to the developing metanephros by using immunohistochemistry and reverse
      transcriptase-polymerase chain reaction for the detection of P1 and/or P2
      promoter-derived products. In adult mouse tissues, the kidney was the only organ
      expressing Hnf4alpha controlled only by the P1 promoter, and HNF4alpha was
      detected in the nuclei of epithelial cells in the proximal tubules, but not in
      other components of the nephron. In the metanephros, HNF4alpha was detected first
      at the epithelial cell nuclei in part of the comma-shaped body, distributed
      widely throughout the developing nephron and finally restricted to the proximal
      tubules. Interestingly, it was noted that Hnf4alpha mRNAs from stomach, pancreas
      and kidney tissues in embryonic periods were transcribed by both promoters.
      Immunohistochemistry for HNF4alpha and HNF1alpha revealed that both factors
      involved the same network of transcription factors, giving the impression that
      HNF4alpha was upstream of HNF1alpha.

PMID- 18803631
TI  - Tympanic ossicles and pharyngeal arches.
AB  - We have performed a study on 11 human embryos regarding the development of the
      tympanic ossicles and their relationship with the first pharyngeal arch. After
      performing measurements to date the embryos and foetuses chronologically, we
      performed a meticulous dissection of the temporal bones. Subsequently, they were
      fixed in 10% formol, decalcified with 2% nitric acid, embedded in Paraplast,
      sectioned in 7-mm sequences and stained with Martin's trichrome technique. In the
      21- and 24-mm cranium-raquis (CR) length human embryos, we have observed the head
      of the malleus and the body of the incus close to Meckel's cartilage, in addition
      to the handle of the malleus, the long limb of the incus and the stapes. Between
      them there was a mesenchymal band inside the primordium of the tympanic cavity.
      In the 27-mm CR embryo, the various components of the malleus and incus were
      fusing, and in the 30-mm CR embryo the union was complete. From our observations,
      we can conclude that the malleus and the incus are derived from the first and
      second pharyngeal arches.

PMID- 18803632
TI  - CT-soft tissue window of the cranial abdomen in clinically normal dogs: an
      anatomical description using macroscopic cross-sections with vascular injection.
AB  - The aim of this study was to provide a detailed anatomic atlas of the cranial
      abdomen by means of computed tomography (CT). Three mature dogs, all mixed breed
      males, were used. The dogs were sedated, anaesthetized and positioned in sternal
      recumbency. CT scans from the eighth thoracic vertebra to the fourth lumbar
      vertebra were performed using a third-generation equipment (TOSHIBA 600HQ
      scanner) with 1 cm slice thickness. CT-images of the cranial abdomen were taken
      with soft-tissue window (WL: -14, WW: 658) settings. Dogs were killed and
      vascular-injection technique was performed: red and blue latex filled the
      vascular system. Injected dogs were frozen in the same position as used for CT
      examination and sectioned with an electric bandsaw at 1-cm-thick intervals. The
      cuts matched as closely as possible to the CT-images. The anatomic sections were
      compared and studied with the corresponding CT-images, and clinically relevant
      abdominal anatomic structures were identified and labelled on the corresponding
      CT-images. The results of our study could be used as a reference for evaluating
      CT-images of the canine cranial abdomen with abdominal diseases.

PMID- 18803633
TI  - Gross and microscopic anatomy of the pineal gland in Nasua nasua--coati
      (Linnaeus, 1766).
AB  - Nasua nasua, coati, is a mammal of the Carnivora order and Procyonidae family. It
      lives in bands composed of females and young males. The pineal gland or epiphysis
      of brain is endocrine, producing the melatonin. Its function is the control of
      the cycle of light environment, characteristic of day and night. For this
      research, five adult coatis were used, originating from CECRIMPAS-UNIfeob (Proc.
      IBAMA 02027.003731/04-76), Brazil. The animals were killed and perfusion-fixed in
      10% formaldehyde. Pineals were measured and a medium size was found to be 2.3-mm
      long and 1.3-mm-wide. Pineal gland was located in the habenular commissure in the
      most caudal portion of the third ventricular roof, lying in a dorso-caudal
      position from the base to the apex. Pinealocytes were predominantly found in the
      glandular parenchyma. Distinct and heterogeneous arrangements of these cells
      throughout the three pineal portions were observed as follows: linear cords at
      the apex, circular cords at the base of the gland, whereas at the body a
      transition arrangement was found. Calcareous concretions could be observed in the
      apex. The pineal gland was classified as subcallosal type [Rec. Med. Vet.1, 36
      (1956)] and as AB type [Prog. Brain Res. 42, 25 (1979); The Pineal Organ,
      Berlin/Heidelberg: Springer-Verlag (1981)].

PMID- 18803634
TI  - In search of the pre- and post-neolithic genetic substrates in Iberia: evidence
      from Y-chromosome in Pyrenean populations.
AB  - The male-mediated genetic legacy of the Pyrenean population was assessed through
      the analysis of 12 Y-STR and 27 Y-SNP loci in a sample of 169 males from 5 main
      geographical areas in the Spanish Pyrenees: Cinco Villas (Western Pyrenees),
      Jacetania and Valle de Aran (Central Pyrenees) and Alto Urgel and Cerdana
      (Eastern Pyrenees). In the Iberian context, the Pyrenean samples present some
      specificities, being characterizeded by a high proportion of chromosomes R1b1b2
      M269 (including the usually uncommon R1b1b2d-SRY(2627) and R1b1b2c-M153 types) or
      I2a2-M26 and low proportions of other haplogroups. Our results indicate that an
      old pre-Neolithic substrate is preponderant in populations of the whole Pyrenean
      fringe. However, AMOVA revealed a high level of substructure within Pyrenean
      populations, partially explained by drift effects as well as by the signature of
      an ancient genetic differentiation between Western and Eastern Pyrenees.

PMID- 18803635
TI  - Analyses of CYP2C in porcine microsomes.
AB  - The cytochrome P450 2C (CYP2C) subfamily in human beings includes four different
      isoenzymes that metabolize different substrates although with some cross
      reactivity. Some of these substrates (e.g. diclofenac and tolbutamide), have been
      investigated in porcine microsomes, but without identifying the specific CYP
      catalysing the reactions. The objective of this study was therefore to test some
      CYP2C substrates and identify the porcine CYP2C responsible for the reaction.
      Three substrates, paclitaxel, tolbutamide and omeprazole, were chosen, as they
      are metabolized by three different CYP2C isoenzymes in human beings. Microsomes,
      isolated from 20 different pigs, 12 conventional, and 8 minipigs, were incubated
      with these compounds, and correlations between the metabolism rates of these
      three substrates were found indicating that the reactions are catalysed by the
      same enzyme. Male minipigs tend to have higher average activity than female
      minipigs, which is in contrast to the gender-dependent expression seen for other
      CYP isoenzymes. The metabolic activities correlated with the protein level
      determined in Western blotting, using anti-human CYP2C9, indicating that this
      enzyme is responsible for the reaction. The expression of the CYP2C enzymes was
      analysed by real-time polymerase chain reaction, using a primer set that could
      amplify CYP2C8, CYP2C9 and CYP2C19. The melting curves (peaks) revealed that all
      three genes were present, showing very different expression levels in the various
      types of pigs. The area of one of the peaks, however, correlated with the CYP2C9
      like enzyme concentration, suggesting that this peak represents CYP2C9. Among
      paclitaxel, tolbutamide and omeprazole, omeprazole is the best probe of CYP2C9
      like enzyme in the pig.

PMID- 18803636
TI  - Anti-inflammatory and analgesic activities of the aqueous extract of Acacia
      karroo stem bark in experimental animals.
AB  - The aqueous extract of the stem bark of Acacia karroo Hayne was investigated for
      its anti-inflammatory and analgesic activities in animal models. The extract at
      100 and 200 mg/kg reduced significantly the formation of oedema induced by
      carrageenan and histamine. In the acetic acid-induced writhing model, the extract
      showed a good analgesic effect characterized by a significant reduction in the
      number of writhes with two doses (100 and 200 mg/kg) used when compared to the
      untreated control group. In the tail immersion test, the extract at the doses
      used (100 and 200 mg/kg) increased reaction time to pain after 30 min. of oral
      administration of the extract. Indomethacin at 10 mg/kg served as reference drug
      in all these tests. The results gave a scientific basis to the traditional uses
      of Acacia karroo mainly for wound poultices, eye treatments and cold remedies.

PMID- 18803637
TI  - Hypoxia-inducible enhancer/alpha-fetoprotein promoter-driven RNA interference
      targeting STK15 suppresses proliferation and induces apoptosis in human
      hepatocellular carcinoma cells.
AB  - STK15 (Aurora A/BTAK) is an oncogenic serine/threonine kinase that plays a role
      in centrosome separation and in the formation of the mitotic bipolar spindle. It
      is highly expressed and constitutively activated in various human tumors
      including hepatocellular carcinoma (HCC). To investigate its possibility as a
      molecular target for future therapies directed against hepatocellular carcinoma,
      we constructed a tissue-specific RNA interference (RNAi) system mediated by
      hypoxia-inducible (HI) enhancer/alpha-fetoprotein (AFP) promoter and employed it
      to downregulate exogenous reporters (LUC and EGFP) and endogenous STK15 gene
      expression and analyzed the phenotypical changes in HCC cells. Results showed
      that the expression of exogenous reporters (LUC and EGFP) was specifically
      downregulated in hepatoma cells but not in non-hepatoma cells. Moreover, the
      specific downregulation of STK15 expression in hepatocellular carcinoma cells
      (HepG2) significantly inhibited in vitro cellular proliferation and in vivo
      tumorigenicity. Furthermore, we also found that the downregulation of STK15
      expression led to cell arrest in the G(2)/M phase and finally apoptosis induction
      of HepG2 cells. Thus, the HI enhancer/AFP promoter-mediated RNAi targeting STK15
      may be a potential therapeutic strategy for the treatment of hepatocellular
      carcinoma with tumor specificity and high efficacy.

PMID- 18803638
TI  - Metformin suppresses intestinal polyp growth in ApcMin/+ mice.
AB  - Metformin is a biguanide derivative that is widely used in the treatment of
      diabetes mellitus. One of the pharmacological targets of metformin is adenosine
      monophosphate-activated protein kinase (AMPK). We investigated the effect of
      metformin on the suppression of intestinal polyp formation in Apc(Min/+) mice.
      Administration of metformin (250 mg/kg) did not reduce the total number of
      intestinal polyp formations, but significantly reduced the number of intestinal
      polyp formations larger than 2 mm in diameter in Apc(Min/+) mice. To examine the
      indirect effect of metformin, the index of insulin resistance and serum lipid
      levels in Apc(Min/+) mice were assessed. These factors were not significantly
      attenuated by the treatment with metformin, indicating that the suppression of
      polyp growth is not due to the indirect drug action. The levels of tumor cell
      proliferation as determined by 5-bromodeoxyuridine and proliferating cell nuclear
      antigen immunohistochemical staining, and apoptosis, via transferase deoxytidyl
      uridine end labeling staining, in the polyps of metformin-treated mice were not
      significantly different in comparison to those of control mice. Gene expression
      of cyclin D1 and c-myc in intestinal polyps were also not significantly different
      between those two groups. In contrast, metformin activated AMPK in the intestinal
      polyps, resulting in the inhibition of the activation of mammalian target of
      rapamycin, which play important roles in the protein synthesis machinery.
      Metformin suppressed the polyp growth in Apc(Min/+) mice, suggesting that it may
      be a novel candidate as a chemopreventive agent for colorectal cancer.

PMID- 18803639
TI  - Extended NO analysis in a healthy subgroup of a random sample from a Swedish
      population.
AB  - INTRODUCTION: There is an interest in modelling exhaled nitric oxide (NO).
      Studies have shown that flow-independent NO parameters i.e. NO of the alveolar
      region (C(A)NO), airway wall (C(aw)NO), diffusing capacity (D(aw)NO) and flux
      (J(aw)NO), are altered in several disease states such as asthma, cystic fibrosis,
      alveolitis and chronic obsmuctive pulmonary disease (COPD). However, values from
      a healthy population are missing. OBJECTIVES: To calculate NO parameters in a
      healthy population by collecting NO values at different exhalation flow rates.
      METHODS: A random sample from the ECRHS II study was investigated. Among the 281
      subjects that had performed a bronchial hyperreactivity (BHR)-test, FEV(1.0), IgE
      and NO-analyses 89 were found to be healthy. RESULTS: There were no differences
      in F(E)NO(0.05) or NO parameters between men and women. There were weak
      correlations between height and both F(E)NO(0.05) (r = 0.23, P = 0.03) and
      C(aw)NO (r = 0.22, P = 0.04). There was also a correlation between age and C(A)NO
      (r = 0.28, P = 0.007). When controlled for gender, this correlation was more
      powerful in women (r = 0.51, P = 0.001) but did not remain for male subjects.
      CONCLUSION: Extended NO analysis is a simple non-invasive tool that gives by far
      more information than F(E)NO(0.05). Based on our results, we suggest that the
      values for healthy subjects should be considered to fall between the following
      ranges: F(E)NO(0.05), 10-30 ppb; C(aw)NO, 50-250 ppb; D(aw)NO, 5-15 ml s(-1);
      J(aw)NO, 0.8-1.6 nl s(-1); and C(A)NO, 0-4 ppb. Values outside these intervals
      indicate the need for further investigation to exclude a state of disease.

PMID- 18803640
TI  - Abnormal respiratory-related evoked potentials in untreated awake patients with
      severe obstructive sleep apnoea syndrome.
AB  - AIM: Obstructive sleep apnoeas generate an intense afferent traffic leading to
      arousal and apnoea termination. Yet a decrease in the sensitivity of the
      afferents has been described in patients with obstructive sleep apnoea, and could
      be a determinant of disease severity. How mechanical changes within the
      respiratory system are processed in the brain can be studied through the analysis
      of airway occlusion-related respiratory-related evoked potentials. Respiratory
      related evoked potentials have been found altered during sleep in mild and
      moderate obstructive sleep apnoea syndrome, with contradictory results during
      wake. We hypothesized that respiratory-related evoked potentials' alterations
      during wake, if indeed a feature of the obstructive sleep apnoea syndrome, should
      be present in untreated severe patients. METHODS: Ten untreated patients with
      severe obstructive sleep apnoea syndrome and eight matched controls were studied.
      Respiratory-related evoked potentials were recorded in Cz-C3 and Cz-C4, and
      described in terms of the amplitudes and latencies of their components P1, N1, P2
      and N2. RESULTS: Components amplitudes were similar in both groups. There was no
      significant difference in P1 latencies. This was also the case for N1 in Cz-C3.
      In contrast, N1 latencies in Cz-C4 were significantly longer in patients with
      obstructive sleep apnoea syndrome [median 98 ms (interquartile range 16.00)
      versus 79.5 ms (5.98), P = 0.015]. P2 and N2 were also significantly delayed, on
      both sides. CONCLUSIONS: The cortical processing of airway occlusion-related
      afferents seems abnormal in untreated patients with severe obstructive sleep
      apnoea syndrome. This could be either a severity marker and/or an aggravating
      factor.

PMID- 18803641
TI  - Oscillometric blood pressure measurement: a simple method in screening for
      peripheral arterial disease.
AB  - Blood pressure at the ankle level is a reliable indicator of peripheral arterial
      disease (PAD) and the ankle brachial index (ABI) is a useful non-invasive
      screening tool for the early detection of atherosclerosis. In the first part of
      the study, systolic blood pressures obtained by oscillometry and plethysmography
      were compared in 80 subjects referred for possible vascular disease. In the
      second part of the study, 31 general practitioners enrolled 1258 consecutive
      patients aged more than 60 years. ABI was estimated by oscillometry. Patients
      with an ABI lower than 0.9 were referred to the local hospital for standardized
      measurements. In the first part, oscillometry showed a sensitivity of 97% and a
      specificity of 62% with a positive and negative predictive value of 71% and 96%,
      respectively. In the second part, significant PAD was found in 111 cases
      corresponding to a prevalence of 12.2%. In this population, the oscillometry
      showed a positive predictive value of 47%. The presence of PAD was significantly
      correlated to exercise related leg pain, a diagnosis of hypertension and smoking,
      whereas no correlation could be found with a diagnosis of heart disease, stroke,
      or with the presence of diabetes. The prevalence of PAD was sufficiently high in
      subjects over the age of 60 years to warrant screening. The ankle brachial index
      based on measurements with an oscillometric device was shown reliable in the
      exclusion of PAD, thereby fulfilling an important criterion for the use in
      screening.

PMID- 18803642
TI  - Oxidative stress in ecology and evolution: lessons from avian studies.
AB  - Although oxidative stress is a central topic in biochemical and medical research,
      the number of reports on its relevance in life-history studies of non-human
      animals is still low. Information about oxidative stress in wild birds may help
      describe functional interactions among the components of life-history traits.
      Currently available evidence suggests that oxidative stress may impart an
      important physiological cost on longevity, reproduction, immune response or
      intense physical activity. Given the gaps in our present knowledge, it is still
      premature to attempt to draw definitive conclusions and basic questions (e.g. how
      is oxidative stress generated and how do organisms cope with it?) have yet to be
      fully explored under natural conditions. Therefore, caution is needed in
      developing hypotheses or drawing general conclusions until additional data become
      available to perform more rigorous comparative analyses.

PMID- 18803643
TI  - Responses of global plant diversity capacity to changes in carbon dioxide
      concentration and climate.
AB  - We model plant species diversity globally by country to show that future plant
      diversity capacity has a strong dependence on changing climate and carbon dioxide
      concentration. CO2 increase, through its impact on net primary production and
      warming is predicted to increase regional diversity capacity, while warming with
      constant CO2 leads to decreases in diversity capacity. Increased CO2
      concentrations are unlikely to counter projected extinctions of endemic species,
      shown in earlier studies to be more strongly dependent on changing land use
      patterns than climate per se. Model predictions were tested against (1)
      contemporary observations of tree species diversity in different biomes, (2) an
      independent global map of contemporary species diversity and (3) time sequences
      of plant naturalisation for different locations. Good agreements between model,
      observations and naturalisation patterns support the suggestion that future
      diversity capacity increases are likely to be filled from a 'cosmopolitan weed
      pool' for which migration appears to be an insignificant barrier.

PMID- 18803644
TI  - Three allometric relations of population density to body mass: theoretical
      integration and empirical tests in 149 food webs.
AB  - Predicting species population density-body mass scaling in community food webs
      (henceforth webs) is important for conservation and to understand community
      structure. Very different types of scaling have been studied, based on either
      individuals or species. The individual size distribution (ISD) describes the
      distribution of individual-organism body masses regardless of taxonomy, and
      contains the same information as the abundance spectrum. Focusing instead on
      species, the local size-density relationship (LSDR) plots population densities
      vs. mean body masses of species. The distribution of species mean body masses
      (the species-mean-size distribution, SMSD) is also important but previously
      little studied in webs. We here combine and formalize theory of several authors
      to predict: how these three descriptions are related; the forms of the LSDR and
      ISD; and variation in scaling among webs. We describe empirically the SMSDs of
      two pelagic, one estuarine, and 146 soil webs by power laws and generalizations.
      We test theory and find it broadly validated.

PMID- 18803645
TI  - Oxygen sensing drives predictable migrations in a microbial community.
AB  - Oxygen sensing is widely practised by aerobic organisms ranging from bacteria to
      vertebrates, and a dominant oxygen-sensing mechanism may persist among all
      aerobes. We traced population migrations of 10 species of the larger aerobic
      ciliated protozoa living in lake sediment, and in the 15 m water column of
      Esthwaite Water in the English Lake District (UK). In so doing, we discovered
      that the character and dynamics of the lake sediment and water column were
      remarkably predictable in performance over a continuous period of almost 2 years.
      Increasing warming of the lake sediment, coupled with low oxygen tension,
      resulted in the emergence of aerobic ciliates out of the sediment and their
      migration into the water column. And with the annual collapse of thermal
      stratification in the water column, the whole annual cycle was repeated. In an
      unusual discovery, we found that particular ciliate species seemed to be 'linked'
      to other (functionally different) ciliate species partners via the ambient oxygen
      tension. The favoured hypothesis is that all ciliate species in a particular body
      size range seek out a particular, preferred oxygen tension. If that is the case,
      the 'cement' providing the cohesion of the ciliate community might actually be
      the preferred oxygen tension. The principal aim of our study is to clarify the
      microbial migration itself, not the response of the different ciliate species to
      oxygen gradients once they have established themselves in the water column. The
      latter happens once the organisms have migrated out of the sediment together,
      driven by the ambient oxygen tension.

PMID- 18803646
TI  - Pan-oceanic distribution of new highly diverse clades of deep-sea diplonemids.
AB  - Molecular rRNA gene surveys reveal a considerable diversity of microbial
      eukaryotes in different environments. Even within a single clade, the number of
      distinct phylotypes retrieved often goes beyond previous expectations. Here, we
      have used specific 18S rRNA PCR primers to investigate the diversity of
      diplonemids, a poorly known group of flagellates with only a few described
      species. We analysed surface and deep-sea plankton samples from different oceanic
      regions, including the water-column in the Marmara Sea. We retrieved a large
      diversity of diplonemid phylotypes, most of which formed two novel distinct
      clades without cultured representatives. Although most marine diplonemid
      phylotypes appeared to be cosmopolitan, they showed a marked stratified
      distribution through the water column, being very scarce or absent in surface
      waters. The small and specific diplonemid diversity found in surface samples and
      the fact that most sequences of uncultured diplonemids found in other studies
      came from deep-sea environments suggest that the two major uncultured diplonemid
      clades group species preferentially inhabit the deep ocean.

PMID- 18803647
TI  - Identification of genes transcribed by Haemophilus parasuis in necrotic porcine
      lung through the selective capture of transcribed sequences (SCOTS).
AB  - Haemophilus parasuis is the aetiological agent of Glasser's disease, which has
      received more attention in the past decade due to the increasing economic losses
      in the pig industry worldwide. Little is known about the mechanisms by which H.
      parasuis survives in the host. In this study, selective capture of transcribed
      sequences (SCOTS) was used to identify H. parasuis genes upregulated in necrotic
      porcine lung 7 days post infection. Thirty-eight genes were identified that were
      upregulated during infection of the lung tissue of pigs, compared with growth in
      culture medium. In two examples chosen gene expression was not confined to the
      lungs, there being variation between tissues. The data support biofilm formation
      being an important mode of growth for colonization and/or persistence. Results
      from the in vitro studies suggest that, as for other pathogens, iron and oxygen
      restriction and heat stress are important environmental signals to regulate gene
      expression. This study has identified genes of H. parasuis that are upregulated
      during infection of porcine lung tissue as compared with in vitro growth
      conditions.

PMID- 18803648
TI  - CSF total and phosphorylated tau protein, regional glucose metabolism and
      dementia severity in Alzheimer's disease.
AB  - BACKGROUND AND PURPOSE: We investigated associations between severity of
      cognitive impairment, cerebrospinal fluid (CSF) concentrations of total-tau (t
      tau) protein and tau phosphorylated at threonin 181 (p-tau(181)) and regional
      glucose metabolism measured with 18F-fluorodeoxyglucose-positron emission
      tomography (18F-FDG-PET) in patients with probable Alzheimer's disease (AD).
      METHODS: In 38 patients (mean age 66.5 +/- 8.0 years) with AD, Mini-Mental State
      Examination (MMSE) scores were evaluated and CSF levels of t-tau and p-tau(181)
      measured. All patients underwent an 18F-FDG-PET scan. Image analysis including
      correlation analysis and principal component analysis (PCA) were performed using
      SPM5 and VINCI. RESULTS: Dementia severity (MMSE 21.2 +/- 4.9) correlated well
      with metabolic impairment especially in left hemisphere association areas that
      are typically affected in patients with AD (e.g. inferior parietal lobule, r =
      0.512; medial temporal gyrus, r = 0.478; inferior temporal gyrus, r = 0.488;
      precuneus, r = 0.468; PCA: r = 0.639, F = 7.751; all P < 0.001). There were no
      associations between t-tau and p-tau(181) with dementia severity and only weak
      correlations between t-tau and cerebral glucose metabolism (superior parietal
      gyrus, r = -0.325, P < 0.05; precentral gyrus r = -0.418, P < 0.01; amygdala r = 
      0.362, P < 0.05). No correlations were found between p-tau(181) and regional
      hypometabolism in FDG-PET. CONCLUSION: MMSE and CSF t-tau represent different
      aspects of disease severity. Whilst MMSE is closely related to impaired cerebral
      glucose metabolism, CSF t-tau is less closely related and appears to be less well
      suited for assessment of disease progression.

PMID- 18803649
TI  - Anxiety undermines quality of life in ALS patients and caregivers.
AB  - BACKGROUND: Although depression has been widely studied in amyotrophic lateral
      sclerosis (ALS), there is little information on anxiety. OBJECTIVE: To detect
      anxiety in patients with ALS and their caregivers, comparing the diagnostic and
      the follow-up phases of the disease and assessing its impact on quality of life
      (QoL). METHODS: Anxiety has been evaluated with the State and Trait Anxiety
      Inventory in a series of 75 consecutive ALS patients and their primary
      caregivers. Anxiety has been related to depression, QoL, and satisfaction with
      life. RESULTS: In patients, state anxiety was significantly higher during the
      diagnostic phase, whilst in caregivers it was similar in the two phases.
      Patients' state anxiety was related to depression, shorter disease duration and
      lower satisfaction with life. Caregivers' state anxiety was related to their
      trait anxiety. Whilst in patients QoL and satisfaction with life were similar in
      the two phases, in caregivers there was a significant decrease of satisfaction
      with life in the follow-up phase. CONCLUSIONS: Treating neurologists should
      recognize that the diagnostic phase and the earlier period after the diagnosis is
      characterized by a high level of anxiety both in ALS patients and in their
      caregivers, and should propose pharmacological and psychological interventions to
      relieve this highly distressing disturbance.

PMID- 18803650
TI  - Intracerebral haemorrhage in a malnourished patient, related to Wernicke's
      encephalopathy.

PMID- 18803651
TI  - Clinical assessment of prognostic factors for long-term pain and handicap after
      whiplash injury: a 1-year prospective study.
AB  - BACKGROUND AND PURPOSE: Physical mechanisms are the possible factors involved in
      the development and maintenance of long-term handicaps after acute whiplash
      injury. This study prospectively examined the role of active neck mobility,
      cervical and extra-cervical pains, as well as non-painful complaints after a
      whiplash injury as predictors for subsequent handicap. METHODS: Consecutive acute
      whiplash patients (n = 688) were interviewed and examined by a study nurse after
      the median of 5 days after injury, and divided into a high- or a low-risk group
      by an algorithm based on pain intensity, number of non-painful complaints and
      active neck mobility [active cervical range of motion (CROM)]. All 458 high-risk
      patients and 230 low-risk patients received mailed questionnaires after 3, 6 and
      12 months. Two examiners examined all high-risk patients (n = 458) and 41
      consecutive low-risk patients at median 11, 109, 380 days after injury. The main
      outcome measures were: handicaps, severe headaches, neck pain and neck
      disability. RESULTS: The relative risk for a 1-year disability increased by 3.5
      with initial intense neck pain and headaches, by 4.6 times with reduced CROM and
      by four times with multiple non-painful complaints. CONCLUSION: Reduced active
      neck mobility, immediate intense neck pain and headaches and the presence of
      multiple non-painful complaints are the important prognostic factors for a 1-year
      handicap after acute whiplash.

PMID- 18803652
TI  - Increased QT variability in cerebral autosomal dominant arteriopathy with
      subcortical infarcts and leukoencephalopathy.
AB  - BACKGROUND AND PURPOSE: Although sudden death (SD) accounts for numerous cases of
      premature mortality in patients with cerebral autosomal dominant arteriopathy
      with subcortical infarcts and leukoencephalopathy (CADASIL), the risk factors
      responsible for this dramatic event remain unclear. We sought possible
      differences in the QT variability index (QTVI) -- a well-known index of temporal
      dispersion in myocardial repolarization strongly associated with the risk of SD -
      between a group of patients with CADASIL and healthy controls. METHODS: A total
      of 13 patients with CADASIL and 13 healthy volunteers underwent a 5-min
      electrocardiogram recording to calculate the QTVI. All the patients also
      underwent a clinical assessment, including functional status by Rankin score, and
      a magnetic resonance imaging (MRI) brain scan for quantitative analysis of T2
      weighted (T2-W) and T1-weighted (T1-W) lesion volume (LV). RESULTS: Short-term QT
      interval analysis showed significantly higher QTVI (P = 0.029) in patients than
      in controls. In patients, notwithstanding the limitations of the small sample
      size, QTVI also well correlated with T1-W LV (r = 0.747, P = 0.003) and T2-W LV
      (r = 0.731, P = 0.005). CONCLUSION: Because patients with CADASIL have increased
      temporal cardiac repolarization variability as assessed by QTVI, this mechanism
      could underlie these patients' risk of SD. Whether this easily assessed, non
      invasive marker could be used to stratify the risk of malignant ventricular
      arrhythmias in patients with CADASIL and, possibly, to guide their therapeutic
      management warrants confirmation from larger prospective studies.

PMID- 18803653
TI  - CSF levels of beta-amyloid 1-42, tau and phosphorylated tau protein in CADASIL.
AB  - BACKGROUND AND PURPOSE: Cerebral autosomal dominant arteriopathy with subcortical
      infarcts and leukoencephalopathy (CADASIL) can be considered a useful model of
      pure subcortical vascular dementia (SVD) because it occurs in young adults,
      unlikely to have concomitant age- and Alzheimer's disease (AD)-related pathology.
      In patients with CADASIL we evaluated the cerebrospinal fluid (CSF) levels of
      beta-amyloid 1-42 (Abeta42), total tau protein (t-tau) and phosphorylated tau
      protein (p-tau), which are well-accepted biomarkers of AD. METHODS: The CSF
      Abeta42, t-tau and p-tau levels were determined with Innotest beta-amyloid 1-42,
      Innotest hTAU-Ag and Innotest Phospho-tau 181p sandwich enzyme-linked
      immunoassay, in 10 CADASIL patients and 17 healthy age-matched subjects. A case
      control statistical analysis was carried out. RESULTS: CSF Abeta42 levels were
      significantly lower in CADASIL patients than in controls, whereas CSF t-tau and p
      tau levels did not differ between the two groups. CONCLUSIONS: The pattern found
      in CADASIL patients is similar to that reported in those with sporadic SVD,
      suggesting that decreased CSF Abeta42 might be related to the subcortical
      vascular lesions in the white matter.

PMID- 18803654
TI  - Manpower of neurologists in the post-socialist countries of Central and Eastern
      Europe.
AB  - BACKGROUND AND PURPOSE: Manpower of neurologists from the post-socialist
      countries of Central and Eastern Europe differs very much from the number of
      neurologists in most of the countries of Western Europe. With the enlargement of
      the European Union (EU), it is necessary to consider the tendencies of manpower
      evolution amongst the 'new' European countries to be able to consider future
      developments, particularly in regard to education and migration. METHODS: A
      survey was performed to study distribution and tendencies to migrate amongst
      neurologists from the post-socialist countries of Central and Eastern Europe.
      RESULTS: The number of neurologists per 10,000 inhabitants varies from one
      country to another, but is higher in the countries of Central and Eastern Europe
      than in most Western European countries. There are almost no available positions
      for neurologists in Eastern Europe, and the majority of neurologists are keen to
      migrate to EU countries -- for further education and for financial reasons.
      CONCLUSIONS: The number of neurologists in the 'reforming and transition'
      countries is considerably higher than in the countries of the EU. Many
      neurologists from these countries would like to migrate to countries of the EU or
      USA, but the existing barriers are difficult to overcome.

PMID- 18803655
TI  - Dichloromethane fraction of Cimicifuga heracleifolia decreases the level of
      melanin synthesis by activating the ERK or AKT signaling pathway in B16F10 cells.
AB  - Cimicifuga rhizoma has long been used in traditional Korean medicine. In
      particular, a Cimicifuga heracleifolia extract (CHE) was reported to inhibit the
      formation of glutamate and the glutamate dehydrogenase activity in cultured rat
      islet. Glutamate activates melanogenesis by activating tyrosinase. Accordingly,
      it was hypothesized that a CHE might inhibit the melanogenesis-related signal
      pathways including the inhibition of microphthalmia-associated transcription
      factor (MITF)-tyrosinase signaling and/or the activation of extracellular signal
      regulated kinase (ERK)-Akt signaling. The results showed that CHE inhibits the
      cellular melanin contents, tyrosinase activity and expression of melanogenesis
      related proteins including MITF, tyrosinase and tyrosinase-related protein (TRP)s
      in alpha-melanocyte-stimulating hormone-stimulated B16 cells. Moreover, CHE
      phosphorylates MEK, ERK1/2 and Akt, which are melanogenesis inhibitory proteins.
      The data suggest that CHE inhibits melanogenesis signaling by both inhibiting the
      tyrosinase directly and activating the MEK-ERK or Akt signal pathways-mediated
      suppression of MITF and its downstream signal pathway, including tyrosinase and
      TRPs. Therefore, C. heracleifolia would be a useful therapeutic agent for
      treating hyperpigmentation and an effective component in whitening and/or
      lightening cosmetics.

PMID- 18803656
TI  - Promotion of incisional wound repair by human mesenchymal stem cell
      transplantation.
AB  - The purpose of this study was to determine the effect of transplanted human
      mesenchymal stem cells (hMSCs) on wound healing. In this model, full-thickness
      cutaneous wounds were created by incision in the skin of adult New Zealand white
      rabbits and treated by transplanted hMSCs into the wounds. Wound healing was
      evaluated by histological analysis and tensiometry over time. A total of 15 New
      Zealand white rabbits with 10 wounds per animal were examined in this study.
      Animals were treated with hMSCs and euthanised at 3, 7, 14, 21 and 80 days after
      manipulation. The hMSCs were labelled with a fluorescent dye (CM-DiI), suspended
      in phosphate-buffered saline and used to treat full-thickness incisional wounds
      in rabbit skin. Tensiometry and histology were used to characterise the wound
      healing rate of the incisional wounds. These results showed that transplanted
      hMSCs significantly inhibited scar formation and increased the tensile strength
      of the wounds. Importantly, MSCs from genetically unrelated donors did not appear
      to induce an immunologic response. In conclusion, human mesenchymal stem cell
      therapy is a viable approach to significantly affect the course of normal
      cutaneous wound healing and significantly increase the tensile strength.

PMID- 18803657
TI  - Vasculitis of small blood vessels--some riddles about IgA and about the
      complexity of transmigration.
AB  - Research on leukocytoclastic vasculitis (LcV) provides insights into mechanisms
      of antibody-mediated immune responses as well as into the complex process of
      neutrophil transmigration. Clinical observations on immune complex vasculitis
      have revealed that adult patients with IgA containing immune complexes [Henoch
      Schoenlein purpura (HSP)] have a higher rate of severe complications than
      children with HSP or adult patients with IgG or IgM containing immune complexes.
      This has direct impact on classification and management of vasculitis and
      warrants further studies on pathophysiology of IgA and on aberrant glycosylation
      of IgA1 associated with renal involvement. In order to dissect the
      pathomechanisms specific for LcV, we have been comparing different mouse models
      of LcV with a non-vasculitic, acute inflammation (i.e. irritant contact
      dermatitis). We found that one characteristic constellation in the vasculitis
      models encompasses interference with both normal transmigration and activation of
      neutrophils. Toxic products released by activated neutrophils have the potential
      to damage endothelial cells. However, one still needs to reveal how exactly they
      exert such damaging effects during diapedesis in vivo, considering the short
      contacts between neutrophils and endothelial cells. This review shows that
      research on LcV is embedded in an exciting context revealing special features of
      transmigration and antibody-mediated immune responses.

PMID- 18803658
TI  - Astaxanthin, canthaxanthin and beta-carotene differently affect UVA-induced
      oxidative damage and expression of oxidative stress-responsive enzymes.
AB  - Carotenoids are used for systemic photoprotection in humans. Regarding mechanisms
      underlying photoprotective effects of carotenoids, here we compared the
      modulation of UVA-related injury by carotenoids. Human dermal fibroblasts (HDF)
      were exposed to moderate doses of UVA, which stimulated apoptosis, increased
      levels of reactive oxygen species and thiobarbituric acid reactive substances,
      decreased antioxidant enzymes activities, promoted membrane perturbation, and
      induced the expression of heme oxygenase-1 (HO-1). The carotenoids astaxanthin
      (AX), canthaxanthin (CX) and beta-carotene (betaC) were delivered to HDF 24 h
      before exposure to UVA. Astaxanthin exhibited a pronounced photoprotective effect
      and counteracted all of the above-mentioned UVA-induced alterations to a
      significant extent. beta-Carotene only partially prevented the UVA-induced
      decline of catalase and superoxide dismutase activities, but it increased
      membrane damage and stimulated HO-1 expression. Moreover, betaC dose-dependently
      induced caspase-3 activity following UVA exposure. In contrast, CX had no effect
      on oxidative damage, except for HO-1 expression, which was augmented. Uptake of
      AX by fibroblasts was higher than that of the other two carotenoids. The
      photostability of the three compounds in fibroblasts was AX > CX >> betaC. The
      data indicate that the oxo-carotenoid AX has a superior preventive effect towards
      photo-oxidative changes in cell culture.

PMID- 18803659
TI  - Autosomal recessive woolly hair with hypotrichosis caused by a novel homozygous
      mutation in the P2RY5 gene.
AB  - During the last decade, several causative genes for hereditary hair diseases have
      been identified, which have disclosed the molecular mechanisms involved in hair
      follicle morphogenesis and cycling. We and others recently reported that
      mutations in the P2RY5 gene, encoding an orphan G protein-coupled receptor,
      underlie autosomal recessive woolly hair (WH)/hypotrichosis. Although these
      findings clearly reveal the involvement of P2RY5 mutations in hereditary hair
      diseases, the clinical manifestations of P2RY5 mutations have not completely been
      elucidated because of limited information to date. In this study, we ascertained
      a consanguineous family of Iranian origin with an affected girl showing sparse
      and hypopigmented scalp hair. She exhibited the WH phenotype with normal hair
      density at birth, but progressed with age to develop hypotrichosis. Direct
      sequencing analysis resulted in the identification of a novel homozygous mutation
      in the P2RY5 gene of the patient, which results in a non-conservative amino acid
      change, G146R, at the protein level. Our findings extend the mutation spectrum of
      P2RY5 mutations, and further support a crucial role of P2Y5 in hair growth in
      humans.

PMID- 18803660
TI  - Evaluation of the role of human herpes virus 6 and 8 in parapsoriasis.
AB  - INTRODUCTION: The aetiology of mycosis fungoides and parapsoriasis (which may be
      considered as an early stage of mycosis fungoides) remains debated. Previous
      recent studies have suspected the involvement of viral agents and particularly
      human herpes viruses (HHV).The aim of the present study was to screen for the
      presence of HHV-6 and HHV-8 genome in parapsoriasis samples. METHOD: Fifty
      paraffin-embedded samples from skin biopsies of parapsoriasis were
      retrospectively collected from archival files in our Dermatology department.
      Total DNA was extracted from samples using the phenol-chloroform method and the
      presence of viral genomes was screened using real-time PCR. RESULTS: Forty nine
      out of the fifty tissue samples of parapsoriasis were interpretable, they were
      all found negative for HHV-6 and HHV-8. DISCUSSION: This study does not confirm
      the suspected role of HHV-6 or -8 in parapsoriasis. HHV-8 has been the most
      studied virus in parapsoriasis and more widely in cutaneous lymphoproliferative
      diseases and our results are in agreement with most of the studies which found
      none or few HHV-8 in more advanced stages of cutaneous lymphoproliferative
      diseases. Concerning HHV-6, our study is the first one investigating the presence
      of this virus in lesional tissue samples of patients with parapsoriasis. In
      conclusion, parapsoriasis does not seem to be associated with either HHV-6 or HHV
      8.

PMID- 18803661
TI  - Epilysin (MMP-28)--structure, expression and potential functions.
AB  - Epilysin (MMP-28) is the newest member of the matrix metalloproteinase (MMP)
      family of extracellular proteases. Together the MMPs can degrade almost all
      components of the extracellular matrix (ECM). MMPs also regulate cell behaviour
      by releasing growth factors and biologically active peptides from the ECM by
      modulating cell surface receptors and adhesion molecules and by regulating the
      activity of mediators of the inflammatory pathways. Epilysin differs from most
      other MMPs as it is expressed in a number of normal tissues, suggestive of
      functions in tissue homeostasis. The epilysin homologue in Xenopus laevis (XMMP
      28) is expressed in neural tissues, where it cleaves the neural cell adhesion
      molecule. Enhanced expression of epilysin has been observed in basal
      keratinocytes during wound healing and in different forms of cancer. There are,
      however, also reports on the downregulation of epilysin in malignant cells. The
      roles of epilysin in cancer seem to vary based on tumor type and stage of the
      disease. Importantly, epilysin can induce stable epithelial to mesenchymal
      transition (EMT) when overexpressed in epithelial lung carcinoma cells.
      Transforming growth factor beta (TGF-beta) is a crucial mediator of this process,
      which was characterized by the loss of E-cadherin and increased cell migration
      and invasion. Current results suggest a plausible interaction between epilysin
      and TGF-beta also under physiological circumstances, where epilysin activity may
      not induce EMT but, instead, trigger less permanent changes in TGF-beta
      signalling and cell motility.

PMID- 18803662
TI  - Corticotropin-releasing factor decreases IL-18 in the monocyte-derived dendritic
      cell.
AB  - Recent evidence suggests that crosstalk between mast cells, nerves and
      keratinocytes might be involved in the exacerbation of inflammatory conditions by
      stress, but the mechanism by which this occurs remains unclear. Corticotropin
      releasing factor (CRF), which activates the hypothalamo-pituitary-adrenal (HPA)
      axis under stress, also has pro-inflammatory peripheral effects. However, there
      have been no reports about CRF receptor expression and the functional role of CRF
      in the dendritic cell (DC), which is considered to be the link between allergen
      uptake and the clinical manifestations of allergic diseases, such as atopic
      dermatitis. The purpose of this study was to investigate the expression of CRF
      receptors and the functional role of CRF in the monocyte-derived DC (MoDC) of
      atopic dermatitis patients and non-atopic healthy controls. In this study, mRNAs
      for CRF-R1alpha and 1beta, as well as the CRF-R1 protein, were detected in MoDCs.
      CRF-R2alpha (but not R2beta or R2gamma) mRNA and the CRF-R2 protein were present
      in MoDCs. Exposure of DCs to CRF resulted in a decrease of IL-18 in both atopic
      dermatitis patients and non-atopic healthy controls. However, CRF did not alter
      the expression of IL-6, CCL17, CCL18, and CCL22. Therefore, our results
      demonstrate that CRF could modulate immune responses by acting directly upon DCs.

PMID- 18803663
TI  - The role of metabolic memory in the ATP paradox and energy homeostasis.
AB  - In yeast, a sudden transition from glucose limitation to glucose excess leads to
      a new steady state at increased metabolic fluxes with a sustained decrease in the
      ATP concentration. Although this behaviour has been rationalized as an adaptive
      metabolic strategy, the mechanism behind it remains unclear. Nevertheless, it is
      thought that, on glucose addition, a metabolite derived from glycolysis may up
      regulate ATP-consuming reactions. The adenine nucleotides themselves have been
      ruled out as the signals that mediate this regulation. This is mainly because, in
      that case, it would be expected that the new steady state at increased fluxes
      would be accompanied by an increased stationary ATP concentration. In this study,
      we present a core model consisting of a monocyclic interconvertible enzyme
      system. Using a supply-demand approach, we demonstrate that this system can
      account for the empirical observations without involving metabolites other than
      the adenine nucleotides as effectors. Moreover, memory is an emerging property of
      such a system, which may allow the cell to sense both the current energy status
      and the direction of the changes.

PMID- 18803664
TI  - Calmodulin binds to maize lipid transfer protein and modulates its lipids binding
      ability.
AB  - Although plant non-specific lipid transfer proteins (ns-LTPs) are characterized
      by their ability to bind and transfer a broad range of hydrophobic ligands in
      vitro, their biological functions in vivo remain unclear. Recently, it has been
      proposed that ns-LTPs may play a key role in plant defense mechanisms,
      particularly during the induction of systemic acquired resistance, however, very
      little is known about the regulation in this process. We report that the binding
      of maize non-specific lipid transfer protein (Zm-LTP) to calmodulin (CaM) is in a
      calcium-independent manner. To better understand the interaction mechanism
      between Zm-LTP and CaM, the CaM-binding site of Zm-LTP was mapped to the region
      of amino acids 46-60. Point mutations indicate that four amino acid residues,
      R46, R47, K54 and R58, in this region are crucial for binding. Furthermore, we
      tested the effects of CaM on the lipid-binding activity of Zm-LTP in the presence
      of Ca(2+), EGTA, N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide and
      trifluoperazine respectively. We also investigated the structural features of CaM
      binding motifs in LTPs from different species and strong differences were
      observed. Taken together, our results suggest that the interaction with CaM could
      be a common feature of plant LTPs. The identification and characterization of CaM
      binding domain of LTPs should provide new insights into the mechanism by which
      the physiological functions of LTPs are regulated.

PMID- 18803665
TI  - DNA methylation-mediated nucleosome dynamics and oncogenic Ras signaling:
      insights from FAS, FAS ligand and RASSF1A.
AB  - Cytosine methylation at the 5-carbon position is the only known stable base
      modification found in the mammalian genome. The organization and modification of
      chromatin is a key factor in programming gene expression patterns. Recent
      findings suggest that DNA methylation at the junction of transcription initiation
      and elongation plays a critical role in suppression of transcription. This effect
      is mechanistically mediated by the state of chromatin modification. DNA
      methylation attracts binding of methyl-CpG-binding domain proteins that trigger
      repression of transcription, whereas DNA demethylation facilitates transcription
      activation. Understanding the rules that guide differential gene expression, as
      well as transcription dynamics and transcript abundance, has proven to be a
      taxing problem for molecular biologists and oncologists alike. The use of novel
      molecular modeling methods is providing exciting insights into the challenging
      problem of how methylation mediates chromatin dynamics. New data implicate lipid
      rafts as the coordinators of signals emanating from the cell membrane and are
      converging on the mechanisms linking DNA methylation and chromatin dynamics. This
      review focuses on some of these recent advances and uses lipid-raft-facilitated
      Ras signaling as a paradigm for understanding DNA methylation, chromatin dynamics
      and apoptosis.

PMID- 18803666
TI  - Role for nectin-1 in herpes simplex virus 1 entry and spread in human retinal
      pigment epithelial cells.
AB  - Herpes simplex virus 1 (HSV-1) demonstrates a unique ability to infect a variety
      of host cell types. Retinal pigment epithelial (RPE) cells form the outermost
      layer of the retina and provide a potential target for viral invasion and
      permanent vision impairment. Here we examine the initial cellular and molecular
      mechanisms that facilitate HSV-1 invasion of human RPE cells. High-resolution
      confocal microscopy demonstrated initial interaction of green fluorescent protein
      (GFP)-tagged virions with filopodia-like structures present on cell surfaces.
      Unidirectional movement of the virions on filopodia to the cell body was detected
      by live cell imaging of RPE cells, which demonstrated susceptibility to pH
      dependent HSV-1 entry and replication. Use of RT-PCR indicated expression of
      nectin-1, herpes virus entry mediator (HVEM) and 3-O-sulfotransferase-3 (as a
      surrogate marker for 3-O-sulfated heparan sulfate). HVEM and nectin-1 expression
      was subsequently verified by flow cytometry. Nectin-1 expression in murine
      retinal tissue was also demonstrated by immunohistochemistry. Antibodies against
      nectin-1, but not HVEM, were able to block HSV-1 infection. Similar blocking
      effects were seen with a small interfering RNA construct specifically directed
      against nectin-1, which also blocked RPE cell fusion with HSV-1 glycoprotein
      expressing Chinese hamster ovary (CHO-K1) cells. Anti-nectin-1 antibodies and F
      actin depolymerizers were also successful in blocking the cytoskeletal changes
      that occur upon HSV-1 entry into cells. Our findings shed new light on the
      cellular and molecular mechanisms that help the virus to enter the cells of the
      inner eye.

PMID- 18803667
TI  - Inactivation of colicin Y by intramembrane helix-helix interaction with its
      immunity protein.
AB  - The construction of hybrids between colicins U and Y and the mutagenesis of the
      colicin Y gene (cya) have revealed amino acid residues important for interactions
      between colicin Y and its cognate immunity protein (Cyi). Four such residues
      (I578, T582, Y586 and V590) were found in helices 8 and 9 of the colicin Y pore
      forming domain. To verify the importance of these residues, the corresponding
      amino acids in the colicin B protein were mutated to the residues present in
      colicin Y. An Escherichia coli strain with cloned colicin Y immunity gene (cyi)
      inactivated this mutant, but not the wild-type colicin B. In addition,
      interacting amino acid pairs in Cya and Cyi were identified using a set of Cyi
      point mutant strains. These data are consistent with antiparallel helix-helix
      interactions between Cyi helix T3 and Cya helix 8 of the pore-forming domain as a
      molecular mechanism of colicin Y inactivation by its immunity protein.

PMID- 18803668
TI  - Antimicrobial effects of H4-(86-100), histogranin and related compounds--possible
      involvement of DNA gyrase.
AB  - Histone-derived antimicrobial peptides have been identified in various organisms
      from plants to humans. The rat histone H4 mRNA variants, H4-v.1 and rat
      histogranin (HNr) mRNAs, were recently reported to be involved in the synthesis
      of H4-(86-100) and its related peptide HNr, respectively. Herein, the two
      peptides were investigated for putative antimicrobial activity and found to
      inhibit growth of gram-negative (Escherichia coli, Pseudomonas aeruginosa) and
      gram-positive (Bacillus subtilis, Staphylococcus aureus) bacteria. Their
      inhibitory potencies in E. coli (LD(50): 3.48 and 4.34 microg x mL(-1)) are
      comparable to that of the antimicrobial peptide LL-37 (LD(50): 4.10 microg x mL(
      1)). The antimicrobial activities of H4-(86-100) and HNr depend upon the
      integrity of the molecules, as precursors [H4-(84-102), pro-HNr] and fragments
      [bovine histogranin (HNb)-(1-13), HNb-(3-13), H4-(89-102) or OGP] are at least
      five times less potent than the parent peptides. Among various HN-like compounds,
      cyclo-(-Gly-pCl-Phe-Tyr-D-Arg) (compound 3) and N-5-guanidino pentanamide-(2R)-yl
      2-N-(p-hydroxyphenylacetyl)-4-(p-chlorobenzoyl)-phenylene diamine (compound 8)
      display antimicrobial activities comparable to that of HNr. Interestingly, the
      antimicrobial activities of H4-(86-100), HNr and compound 3, like those of
      quinolone antibiotics acting as DNA gyrase poisons, are potentiated by ATP (1 mM)
      and coumermycin A1 (a DNA gyrase-linked ATPase inhibitor) and blocked by 2,4
      dinitrophenol (DNP, an uncoupler of oxidative phosphorylation) and fluoroacetic
      acid (a metabolic poison). Finally, in vitro experiments indicate that H4-(86
      100), HNr, compound 3 and compound 8, but not HNb-(1-13) or HNb-(3-13), inhibit
      DNA gyrase-mediated supercoiling of pBR322 DNA. These data indicate that the
      naturally occurring H4-(86-100) and HNr display antimicrobial effects that
      involve a modulation of ATP-dependent DNA gyrase.

PMID- 18803669
TI  - Insight into the mechanisms of aminoglycoside derivatives interaction with HIV-1
      entry steps and viral gene transcription.
AB  - In recent years, based on peptide models of HIV-1 RNA binding, NMR structures of
      Tat-responsive element-ligand complexes and aminoglycoside-RNA interactions, and
      HIV-1 Tat structure, we have designed and synthesized aminoglycoside-arginine
      conjugates (AACs) and aminoglycoside poly-arginine conjugates (APACs), to serve
      as Tat mimetics. These novel molecules inhibit HIV-1 infectivity with 50%
      effective concentration values in the low micromolar range, the most potent
      compounds being the hexa-arginine-neomycin B and nona-D-arginine-neomycin
      conjugates. Importantly, these compounds, in addition to acting as Tat
      antagonists, inhibit HIV-1 infectivity by blocking several steps in HIV-1 cell
      entry. The AACs and APACs inhibit HIV-1 cell entry by interacting with gp120 at
      the CD4-binding site, by interacting with CXCR4 at the binding site of the CXCR4
      mAb 12G5, and apparently by interacting with transient structures of the
      ectodomain of gp41. In the current review, we discuss the mechanisms of anti-HIV
      1 activities of these AACs, APACs and other aminoglycoside derivatives in detail.
      Targeting several key processes in the viral life cycle by the same compound not
      only may increase its antiviral efficacy, but more importantly, may reduce the
      capacity of the virus to develop resistance to the compound. AACs and APACs may
      thus serve as leading compounds for the development of multitargeting novel HIV-1
      inhibitors.

PMID- 18803670
TI  - Metabolic response of Pseudomonas putida during redox biocatalysis in the
      presence of a second octanol phase.
AB  - A key limitation of whole-cell redox biocatalysis for the production of valuable,
      specifically functionalized products is substrate/product toxicity, which can
      potentially be overcome by using solvent-tolerant micro-organisms. To investigate
      the inter-relationship of solvent tolerance and energy-dependent biocatalysis, we
      established a model system for biocatalysis in the presence of toxic low logP(ow)
      solvents: recombinant solvent-tolerant Pseudomonas putida DOT-T1E catalyzing the
      stereospecific epoxidation of styrene in an aqueous/octanol two-liquid phase
      reaction medium. Using (13)C tracer based metabolic flux analysis, we
      investigated the central carbon and energy metabolism and quantified the NAD(P)H
      regeneration rate in the presence of toxic solvents and during redox
      biocatalysis, which both drastically increased the energy demands of solvent
      tolerant P. putida. According to the driven by demand concept, the NAD(P)H
      regeneration rate was increased up to eightfold by two mechanisms: (a) an
      increase in glucose uptake rate without secretion of metabolic side products, and
      (b) reduced biomass formation. However, in the presence of octanol, only
      approximately 1% of the maximally observed NAD(P)H regeneration rate could be
      exploited for styrene epoxidation, of which the rate was more than threefold
      lower compared with operation with a non-toxic solvent. This points to a high
      energy and redox cofactor demand for cell maintenance, which limits redox
      biocatalysis in the presence of octanol. An estimated upper bound for the NAD(P)H
      regeneration rate available for biocatalysis suggests that cofactor availability
      does not limit redox biocatalysis under optimized conditions, for example, in the
      absence of toxic solvent, and illustrates the high metabolic capacity of solvent
      tolerant P. putida. This study shows that solvent-tolerant P. putida have the
      remarkable ability to compensate for high energy demands by boosting their energy
      metabolism to levels up to an order of magnitude higher than those observed
      during unlimited growth.

PMID- 18803672
TI  - A putative lipoprotein of Sphingomonas sp. strain A1 binds alginate rather than a
      lipid moiety.
AB  - Gram-negative Sphingomonas sp. strain A1 accumulates alginate in the cell surface
      pit and directly incorporates the polysaccharide into its cytoplasm through a
      'superchannel'. A cell surface protein Algp7 (27 kDa) is inducibly expressed in
      the presence of alginate. Although the protein Algp7 was initially classified as
      a lipoprotein based on its primary structure, Algp7 purified from strain A1 cells
      did not possess a lipid moiety. Algp7 bound alginate efficiently at a neutral pH
      with a K(d) of 3.6 x 10(-8) M, suggesting that the cell surface protein
      contributed to accumulation of alginate in the pit.

PMID- 18803671
TI  - Structure of bacterial communities along a hydrocarbon contamination gradient in
      a coastal sediment.
AB  - The bacterial diversity of a chronically oil-polluted retention basin sediment
      located in the Berre lagoon (Etang-de-Berre, France) was investigated. This study
      combines chemical and molecular approaches in order to define how the in situ
      petroleum hydrocarbon contamination level affects the bacterial community
      structure of a subsurface sediment. Hydrocarbon content analysis clearly revealed
      a gradient of hydrocarbon contamination in both the water and the sediment
      following the basin periphery from the pollution input to the lagoon water. The
      nC17 and pristane concentrations suggested alkane biodegradation in the
      sediments. These results, combined with those of terminal-restriction fragment
      length polymorphism analysis of the 16S rRNA genes, indicated that bacterial
      community structure was obviously associated with the gradient of oil
      contamination. The analysis of bacterial community composition revealed dominance
      of bacteria related to the Proteobacteria phylum (Gamma-, Delta-, Alpha-, Epsilon
      and Betaproteobacteria), Bacteroidetes and Verrucomicrobium groups and
      Spirochaetes, Actinobacteria and Cyanobacteria phyla. The adaptation of the
      bacterial community to oil contamination was not characterized by dominance of
      known oil-degrading bacteria, because a predominance of populations associated to
      the sulphur cycle was observed. The input station presented particular bacterial
      community composition associated with a low oil concentration in the sediment,
      indicating the adaptation of this community to the oil contamination.

PMID- 18803673
TI  - Dissimilatory ferrous iron oxidation at a low pH: a novel trait identified in the
      bacterial subclass Rubrobacteridae.
AB  - A novel iron-oxidizing acidophilic actinobacterium was isolated from spoil
      material at an abandoned copper mine. Phylogenetic analysis placed the isolate
      within the Rubrobacteridae subclass of the Actinobacteria. Its optimum
      temperature and pH for growth are 30-35 degrees C and pH 3.0, respectively.
      Although it could catalyze the dissimilatory oxidation of ferrous iron, growth
      yields declined progressively in media containing ferrous iron concentrations
      >100 microM. The isolate, Pa33, did not grow or oxidize iron in the absence of
      organic carbon, and appeared to be an obligate heterotroph. Specific rates of
      iron oxidation were much smaller than those determined for the autotrophic iron
      oxidizing proteobacterium Acidithiobacillus ferrooxidans and the heterotrophic
      iron-oxidizing actinobacterium Ferrimicrobium acidiphilum. Iron oxidation by
      isolate Pa33 appears to be a defensive mechanism, in which iron oxidation
      converts a soluble species to which the bacterium is sensitive to an oxidized
      species (ferric iron) that is highly insoluble in the spoil from which it was
      isolated. This is the first report of acidophily or dissimilatory iron oxidation
      within the Rubrobacteridae subclass and one of very few within the Actinobacteria
      phylum as a whole.

PMID- 18803674
TI  - Copper removal ability by Streptomyces strains with dissimilar growth patterns
      and endowed with cupric reductase activity.
AB  - Morphological, physiological and molecular characterization of three copper
      resistant actinobacterial strains (AB2A, AB3 and AB5A) isolated from copper
      polluted sediments of a drainage channel showed that they belonged to the genus
      Streptomyces. These characteristics plus their distinctive copper resistance
      phenotypes revealed considerable divergence among the isolates. Highly dissimilar
      growth patterns and copper removal efficiency were observed for the selected
      Streptomyces strains grown on minimal medium (MM) added with 0.5 mM of copper
      sulfate (MM(Cu)). Strain AB2A showed an early mechanism of copper
      uptake/retention (80% until day 3), followed by a drastic metal efflux process
      (days 5-7). In contrast, Streptomyces sp. AB3 and AB5A showed only copper
      retention phenotypes under the same culture conditions. Particularly,
      Streptomyces sp. AB5A showed a better efficiency in copper removal (94%),
      although a longer lag phase was observed for this microorganism grown for 7 days
      in MM(Cu). Cupric reductase activity was detected in both copper-adapted cells
      and nonadapted cells of all three strains but this activity was up to 100-fold
      higher in preadapted cells of Streptomyces sp. AB2A. To our knowledge, this is
      the first time that cupric reductase activity was demonstrated in Streptomyces
      strains.

PMID- 18803675
TI  - Microalbuminuria and obesity: impact on cardiovascular disease and mortality.
AB  - OBJECTIVE: Microalbuminuria and obesity are both associated with cardiovascular
      disease (CVD). The aim of this study was to determine the association between
      obesity (measured by body mass index, waist-to-hip ratio, waist circumference)
      and different levels of microalbuminuria. We also aimed to determine the risk of
      death and CVD at different levels of microalbuminuria and obesity. DESIGN:
      Population-based observational study based on 2696 men and women, 30-70 years of
      age. Urinary albumin excretion (UAE), body mass index, waist-to-hip ratio, waist
      circumference and other cardiovascular risk factors were measured during the
      years 1992-1994 at the Copenhagen City Heart Study. End-points were registered
      until 1999-2000 with respect to CVD and until 2004 with respect to death.
      RESULTS: There was a strong association between microalbuminuria and obesity.
      Microalbuminuria and obesity had additive effects on the relative risk of death
      independently of other risk factors. In contrast there was no statistically
      significant association between microalbuminuria and risk of CVD when stratified
      by obesity. CONCLUSIONS: Microalbuminuria (UAE > 5 microg/min) confers increased
      risk of death and to a similar extent as obesity. This effect is independent of
      concomitant obesity. We suggest microalbuminuria to be included in health
      examinations besides measurements of obesity.

PMID- 18803676
TI  - Placental production and maternal serum and urine levels of inhibin A and activin
      A are modified by antihypertensive therapy in hypertensive disorders of
      pregnancy.
AB  - OBJECTIVE: Levels of inhibin A and activin A are raised in pre-eclampsia (PE) but
      it is not known if antihypertensive therapy can affect their levels. Our aim was
      to investigate the effect of the antihypertensive drug alpha-methyldopa on serum,
      urine and placental concentrations of inhibin A and activin A in women presenting
      with hypertensive disorders of pregnancy. DESIGN: This was a cross-sectional
      study. PATIENTS: We recruited 65 women presenting with PE, 39 with gestational
      hypertension (GH) and 104 normotensive controls matched for maternal age,
      gestational age and parity. MEASUREMENTS: Using specific validated ELISAs, serum
      and urine levels of inhibin A and activin A, and uterine artery Doppler indices,
      were measured before and 24-48 h after initiating alpha-methyldopa therapy in
      women with PE, with GH and controls. Protein extracts were obtained from samples
      of placental tissue from another group of women with PE, GH and controls for the
      same analysis. RESULTS: In PE, but not GH, alpha-methyldopa therapy was
      associated with significantly (P < 0.05) lower levels of both serum and urine
      inhibin A and activin A. Similarly, in PE but not GH, alpha-methyldopa therapy
      was associated with lower placental levels of both markers (P < 0.05). There was
      no significant difference in pulsatility index following treatment in either PE
      or GH. CONCLUSIONS: Our data indicate that antihypertensive therapy with alpha
      methyldopa may have an effect on the synthesis and/or release of placental
      proteins in pregnancies complicated by PE and that this effect may be independent
      of its known antihypertensive action.

PMID- 18803677
TI  - High dose cabergoline therapy for a resistant macroprolactinoma during pregnancy.

PMID- 18803678
TI  - Quality of life changes and clinical outcomes in thyroid cancer patients
      undergoing radioiodine remnant ablation (RRA) with recombinant human TSH (rhTSH):
      a randomized controlled study.
AB  - BACKGROUND: Recombinant human TSH (rhTSH) has become the modality of choice for
      radioiodine remnant ablation (RRA) in low-risk thyroid cancer patients. AIMS AND
      METHODS: The aims of the present prospective randomized study were to evaluate
      the impact of TSH stimulation procedure (hypothyroidism vs. rhTSH) on quality of
      life (QoL) of thyroid cancer patients undergoing RRA and to evaluate efficacy of
      both procedures. L-T4 was initiated in both groups after thyroidectomy. After
      randomization, L-T4 was discontinued in hypothyroid (hypo) group and continued in
      rhTSH group. A measure of 3.7 GBq of radioiodine was given to both groups. The
      functional assessment of chronic illness therapy-fatigue (FACIT-F) was
      administered from the early postoperative period to 9 months. Socio-demographic
      parameters, anxiety and depression scales were also evaluated (CES-D, BDI and
      Spielberger state-trait questionnaires). At 9 months, patients underwent an rhTSH
      stimulation test, diagnostic (131)I whole body scan (dxWBS) and neck
      ultrasonography. RESULTS: A total of 74 patients were enrolled for the study.
      There was a significant decrease in QoL from baseline (t0) to t1 (RRA period) in
      the hypothyroid group with significant differences in FACIT-F TOI (P < 10(-3)),
      FACT-G total score (P = 0.005) and FACIT-F total score (P = 0.003). By contrast,
      QoL was preserved in the rhTSH group. In the multivariate analysis, FACIT-TOI
      changes were only affected by the modality of TSH stimulation performed for RRA.
      From 3 to 9 months, changes of QoL scales and subscales were no longer
      statistically different in both groups of patients. Based on serum rhTSH
      stimulated Tg alone (Tg < 0.8 microg/l, BRAHMS Tg Kryptor), no difference in
      ablation success was observed between rhTSH and hypothyroidism groups, 91.7% and
      97.1%, respectively. A higher rate of persistent thyroid remnants was observed in
      the rhTSH arm, although in most cases uptake was < 0.1% and of no clinical
      significance. CONCLUSIONS: rhTSH preserves QoL of patients undergoing RRA with
      similar rates of ablation success compared to hypothyrodism. However, there is a
      wide heterogeneity in the clinical impact of hypothyroidism.

PMID- 18803679
TI  - Leptin concentration indexed to fat mass is increased in untreated anorexia
      nervosa (AN) patients.
AB  - CONTEXT: Data regarding serum adipocytokine and ghrelin concentrations in
      different stages of anorexia nervosa (AN) is conflicting. OBJECTIVE: Our aim is
      to determine serum concentrations of adiponectin (ApN), leptin and ghrelin in
      different stages of AN and to evaluate their relationships with study parameters.
      DESIGN SETTING AND PARTICIPANTS: Study group was composed of four subgroups:
      Group 1: patients with a recent diagnosis of AN (n = 19); group 2: weight
      recovered (10% increase in body weight compared with baseline) subgroup of group
      1 during follow-up (n = 10); group 3: recovered patients with a previous history
      of AN but normal menstrual cycles and body weight currently (n = 10); group 4:
      control group (n = 10). Venous blood was obtained for measurements of
      biochemical/hormonal parameters, ApN, leptin and ghrelin. Body composition was
      determined by bioimpedance analysis. MAIN OUTCOME MEASURES: Changes in
      adipocytokine and ghrelin concentrations and relationships with
      anthropometric/biochemical parameters. RESULTS: Leptin: fat mass (kg) ratio was
      significantly higher in group 1 patients compared with group 4 (4.3 +/- 4.6 vs.
      1.1 +/- 0.5 microg/l kg, P < 0.01). No significant difference was observed among
      ghrelin concentrations. Leptin showed significant positive correlation with body
      fat mass in all groups. ApN showed significant positive association with body
      mass index in Group 1. CONCLUSIONS: Leptin concentrations indexed to fat mass may
      indicate a nonphysiological higher set point of leptin per unit fat mass in
      treatment-naive AN patients. Correlation pattern between ApN and fat mass is
      modified also. Altered adipocytokine profile in AN may contribute to anorectic
      behaviour.

PMID- 18803680
TI  - Augmentation index in resistance to thyroid hormone (RTH).
AB  - OBJECTIVE: Resistance to thyroid hormone (RTH) is associated with a varied
      clinical presentation. The cardiac effects of RTH have been described but
      vascular function has yet to be fully evaluated in this condition. We have
      measured the arterial function of those with RTH to assess any vascular changes.
      DESIGN: An observational study. PATIENTS: Twelve RTH patients were recruited from
      the thyroid clinic (mean value +/- SD), age 40.8 +/- 18.7 years; BMI 27.2 +/- 4.2
      kg/m(2) and compared with 12 healthy, euthyroid, age-matched controls (age 41.4
      +/- 19.3; BMI 24.8 +/- 4.4 kg/m(2)) with no history of cardiovascular disease. No
      interventional measures were instituted. MEASUREMENTS: Arterial stiffness was
      measured using pulse wave analysis at the radial artery. Thyroid function,
      fasting lipids and glucose were also measured on the same occasion in both
      patients and controls. Results The corrected augmentation index, a surrogate
      marker of arterial stiffness was significantly higher in patients compared with
      controls (21.0% +/- 14.1%vs. 5.4% +/- 18.2%, P < 0.03). Low density lipoprotein
      cholesterol (LDL-cholesterol) levels were also significantly elevated in patients
      compared with controls (3.0 +/- 0.6 vs. 2.1 +/- 0.5 mmol/l; P < 0.002).
      CONCLUSION: RTH patients show evidence in this study of increased augmentation
      index consistent with an increase in arterial stiffness compared with euthyroid
      controls. They also demonstrate elevated LDL-cholesterol levels. Both these
      measures may lead to increased cardiovascular risk.

PMID- 18803681
TI  - Plumage and song differences mediate species recognition between incipient
      flycatcher species of the Solomon Islands.
AB  - Changes in mating signals among populations contribute to species formation.
      Often these signals involve a suite of display traits of different sensory
      modalities ("multimodal signals"); however, few studies have tested the
      consequences of multimodal signal divergence with most focusing on only a single
      divergent signal or suite of signals of the same sensory modality. Populations of
      the chestnut-bellied flycatcher Monarcha castaneiventris vary in song and plumage
      color across the Solomon Islands. Using taxidermic mount presentation and song
      playback experiments, we tested for the relative roles of divergent song and
      color in homotypic ("same type") recognition between one pair of recently
      diverged sister taxa (the nominate chestnut-bellied M. c. castaneiventris and the
      white-capped M. c. richardsii forms). We found that both plumage and song type
      influenced the intensity of aggressive response by territory-owners, with plumage
      color playing a stronger role. These results indicate that differences in plumage
      and song are used in homotypic recognition, suggesting the importance of
      multimodal signal divergence in the evolution of premating reproductive
      isolation.

PMID- 18803682
TI  - Predation's role in repeated phenotypic and genetic divergence of armor in
      threespine stickleback.
AB  - Predator-driven divergent selection may cause differentiation in defensive armor
      in threespine stickleback: (1) predatory fish and birds favor robust armor,
      whereas (2) predaceous aquatic insects favor armor reduction. Although (1) is
      well established, no direct experimental evidence exists for (2). I examined the
      phenotypic and genetic consequences of insect predation using F(2) families from
      crosses between freshwater and marine stickleback populations. I measured
      selection on body size, and size-adjusted spine (dorsal and pelvic) and pelvic
      girdle length, by splitting juvenile F(2) families between control and insect
      predation treatments, set in pond enclosures. I also examined the effect of
      insect predation on Ectodysplasin (Eda), a gene physically linked to quantitative
      trait loci for lateral plate number, spine length, and body shape. Insect
      predation resulted in: (1) significant selection for larger juvenile size, and
      shorter dorsal spine and pelvic girdle length, (2) higher mortality of
      individuals missing the pelvic girdle, and (3) selection in favor of the low
      armor Eda allele. Predatory insects favor less stickleback armor, likely
      contributing to the widespread reduction of armor in freshwater populations.
      Because size strongly influences mate choice, predator-driven divergent selection
      on size may play a substantial role in byproduct reproductive isolation and
      speciation in threespine stickleback.

PMID- 18803683
TI  - Static allometry and animal genitalia.
AB  - A survey of 117 species of arthropods and 17 species of vertebrates showed a
      strong trend for male genitalia to have relatively low static allometric values.
      This trend contrasts with the allometry of other structures under sexual
      selection, which usually show steep allometric slopes. The trend to low
      allometric genital values is less consistent in mammals than in arthropods. Data
      not in accord with the previous the "one-size-fits-all" explanation for low
      allometric slopes in genitalia, which was based on sexual selection by female
      choice, suggest a more general version that includes both natural selection and
      sexual selection, and involves both mechanical fit and stimulation. Less-complete
      data on the female genitalia of arthropods suggest a trend to similar low
      allometric slopes, and may also be explained by mechanical fit and stimulatory
      one-size-fits-all arguments.

PMID- 18803684
TI  - The correlated evolution of three-dimensional reproductive structures between
      male and female damselflies.
AB  - For many taxa, species are defined by the morphologies of reproductive
      structures. In many odonates, these structures are the cerci of males (used to
      hold females during mating) and the thoracic plates of females where the male
      cerci contact the females' bodies. A previous study showed that the shapes of
      cerci of Enallagma males (Zygoptera: Coenagrionidae) are best explained by an
      evolutionary model of punctuated change at the time of speciation, with a
      homogeneous rate of change across the entire phylogeny of the genus. In the
      present study, we examine the evolution of shape change in the corresponding
      female plates. We found that, like male cerci, the shapes of Enallagma female
      thoracic plates could best be explained by an evolutionary model of punctuated
      change at the time of speciation, with a homogeneous rate of change across the
      clade. Moreover, the evolutionary contrasts quantifying the rates of change in
      male cerci and female thoracic plates were positively related across the history
      of the clade, demonstrating that these male and female structures evolve in a
      correlated fashion. This pattern of evolution suggests that these structures are
      primary signals of species identity during mating.

PMID- 18803685
TI  - Genetic analysis of a chromosomal hybrid zone in the Australian morabine
      grasshoppers (Vandiemenella, viatica species group).
AB  - Whether chromosomal rearrangements promote speciation by providing barriers to
      gene exchange between populations is one of the long-standing debates in
      evolutionary biology. This question can be addressed by studying patterns of gene
      flow and selection in hybrid zones between chromosomally diverse taxa. Here we
      present results of the first study of the genetic structure of a hybrid zone
      between chromosomal races of morabine grasshoppers Vandiemenella viatica, P24(XY)
      and viatica17, on Kangaroo Island, Australia. Chromosomal and 11 nuclear markers
      revealed a narrow hybrid zone with strong linkage disequilibrium and heterozygote
      deficits, most likely maintained by a balance between dispersal and selection.
      Widths and positions of clines for these markers are concordant and coincident,
      suggesting that selection is unlikely to be concentrated on a few chromosomes. In
      contrast, a mitochondrial marker showed a significantly wider cline with centre
      offset toward the P24(XY) side. We argue that the discordance between the
      mitochondrial and nuclear/chromosomal clines and overall asymmetry of the clines
      suggest a secondary origin of the contact zone and potential movement of the zone
      after contact. Genome-wide scans using many genetic markers and chromosomal
      mapping of these markers are needed to investigate whether chromosomal
      differences directly reduce gene flow after secondary contact.

PMID- 18803686
TI  - Defeating pathogen drug resistance: guidance from evolutionary theory.
AB  - Many of the greatest challenges in medicine and public health involve the
      evolution of drug resistance by pathogens. Recent advances in the theory of
      natural selection suggest that there are two broad classes of pathogen traits
      that can be targeted by drugs or vaccines. The first class, consisting of traits
      that benefit the individual organisms bearing them, causes a strong evolutionary
      response and the rapid emergence of drug resistance. The second class, consisting
      of traits that benefit groups of pathogen organisms including the individual
      provider, causes a weaker evolutionary response and less drug resistance.
      Although most previous drug development has targeted the first class, it would be
      advantageous to focus on the second class as targets for drug and vaccine
      development. Specific examples and test cases are discussed.

PMID- 18803687
TI  - Multiple direct transitions from sexual reproduction to apomictic parthenogenesis
      in Timema stick insects.
AB  - Transitions from sexual reproduction to parthenogenesis may occur along multiple
      evolutionary pathways and involve various cytological mechanisms to produce
      diploid eggs. Here, we investigate routes to parthenogenesis in Timema stick
      insects, a genus comprising five obligate parthenogens. By combining information
      from microsatellites and karyotypes with a previously published mitochondrial
      phylogeny, we show that all five parthenogens likely evolved spontaneously from
      sexually reproducing species, and that the sexual ancestor of one of the five
      parthenogens was probably of hybrid origin. The complete maintenance of
      heterozygosity between generations in the five parthenogens strongly suggests
      that eggs are produced by apomixis. Virgin females of the sexual species were
      also able to produce parthenogenetic offspring, but these females produced eggs
      by automixis. High heterozygosity levels stemming from conserved ancestral
      alleles in the parthenogens suggest, however, that automixis has not generated
      the current parthenogenetic Timema lineages but that apomixis appeared abruptly
      in several sexual species. A direct transition from sexual reproduction to (at
      least functional) apomixis results in a relatively high level of allelic
      diversity and high efficiency for parthenogenesis. Because both of these traits
      should positively affect the demographic success of asexual lineages, spontaneous
      apomixis may have contributed to the origin and maintenance of asexuality in
      Timema.

PMID- 18803688
TI  - On luck and sex.
AB  - Sex has many costs with respect to asexual reproduction, so its ubiquity is a
      puzzle. There has been a continuing effort to identify general circumstances in
      which aspects of sex generate an evolutionary advantage over asexual
      reproduction. Here we focus on the generality that individuals can experience
      good and bad "luck" at various stages of their life history regardless of
      genotype, and on the interindividual nature of sex. Sexual outcrossing combines
      genetic information from individuals with potentially different experiences, so
      it is conceivable that sex might reduce the contribution of individual luck to
      noise in inheritance. In a simple way, we derive expressions for noise in
      inheritance in terms of some sources of within-generation ecological noise. We
      demonstrate that interindividual reproduction can indeed dampen the effects of
      ecological noise better than lone-individual modes, but there are conditions
      under which it does not. Empirical and theoretical work on plants, modeled here,
      suggest noise dampening conditions. Ecological noise dampening operates alongside
      other features of sex such as recombination and segregation and, because noise in
      inheritance weakens the role of selection in genetic change, we speculate that
      noise dampening may offer a benefit to be deducted from the costs of sex. We also
      suggest that the amount of selfing relative to outcrossing observed in natural
      populations may be influenced by the amount of individual-level ecological noise
      in a given habitat.

PMID- 18803689
TI  - The evolution of high summit metabolism and cold tolerance in birds and its
      impact on present-day distributions.
AB  - Summit metabolic rate (M(sum), maximum cold-induced metabolic rate) is positively
      correlated with cold tolerance in birds, suggesting that high M(sum) is important
      for residency in cold climates. However, the phylogenetic distribution of high
      M(sum) among birds and the impact of its evolution on current distributions are
      not well understood. Two potential adaptive hypotheses might explain the
      phylogenetic distribution of high M(sum) among birds. The cold adaptation
      hypothesis contends that species wintering in cold climates should have higher
      M(sum) than species wintering in warmer climates. The flight adaptation
      hypothesis suggests that volant birds might be capable of generating high M(sum)
      as a byproduct of their muscular capacity for flight; thus, variation in M(sum)
      should be associated with capacity for sustained flight, one indicator of which
      is migration. We collected M(sum) data from the literature for 44 bird species
      and conducted both conventional and phylogenetically informed statistical
      analyses to examine the predictors of M(sum) variation. Significant phylogenetic
      signal was present for log body mass, log mass-adjusted M(sum), and average
      temperature in the winter range. In multiple regression models, log body mass,
      winter temperature, and clade were significant predictors of log M(sum). These
      results are consistent with a role for climate in determining M(sum) in birds,
      but also indicate that phylogenetic signal remains even after accounting for
      associations indicative of adaptation to winter temperature. Migratory strategy
      was never a significant predictor of log M(sum) in multiple regressions, a result
      that is not consistent with the flight adaptation hypothesis.

PMID- 18803690
TI  - Barriers to cross-fertilization between populations of a widely dispersed
      polychaete species are unlikely to have arisen through gametic compatibility arms
      races.
AB  - Although there are theoretical reasons to suspect that gametic incompatibility
      may develop readily among populations of broadcast spawning marine invertebrates,
      there have been very few studies documenting geographic patterns of
      interpopulation incompatibility for any species. To address this we determined
      how successfully individuals of the intertidal serpulid polychaete, Galeolaria
      caespitosa, can cross-fertilize within and among populations from across
      temperate Australia. Fertilization assays revealed asymmetrical differences
      between very distantly located populations from different coasts, with near
      complete incompatibility between eggs from Sydney with sperm from Adelaide, but
      the reverse cross (Adelaide eggs, Sydney sperm) was reasonably compatible.
      Although that pattern was congruent with a clear difference in Cytochrome B
      sequences between worms on the south and east coasts of Australia, we also
      detected some indication of interpopulation incompatibility within the genetic
      grouping on east coast, between two populations separated by only 220 km. We then
      assessed whether commonly proposed gametic compatibility arms-races could account
      for these patterns. Our results suggest reduced gametic compatibility may reduce
      a female's maximum fertilization potential, resulting in a cost to this potential
      mechanism for reducing polyspermy. Consequently, the apparently rapid development
      of reproductive barriers here seems unlikely to have been driven by arms-races
      involving sexual conflict over fertilization rate.

PMID- 18803691
TI  - The ecology of asymmetry in stickleback defense structures.
AB  - Slight departures from bilateral symmetry are usually associated with reduced
      fitness. Here we show that an insular freshwater population of Gasterosteus
      aculeatus exhibits spatial and temporal segregation according to the incidence
      and direction of asymmetry in the number of bony lateral plates, which are
      important predator-defense structures. We analyzed 11,263 fish collected from 19
      full lake transects over three years, and found that signed asymmetries for plate
      number were slightly left-side biased. Asymmetries occurred in 55% of the
      stickleback with more asymmetrics found during cold weather, and more left-biased
      individuals found during windy conditions, possibly due to environmentally driven
      activity levels that differ among asymmetric forms. Absolute plate asymmetries
      were randomly distributed in the lake, but there was a strong shift in signed
      plate asymmetry from a mean of zero in littoral zones to left-side bias in
      limnetic zones, probably due to microhabitat choices among asymmetric forms.
      Video data of avian piscivores on the lake show laterality in prey handling,
      providing a potential mechanism for asymmetric prey morphology. Our results imply
      a complex relationship between slight asymmetries and niche space that is
      relevant to the broader literature on the evolutionary implications of
      developmental instability and intrapopulation variability.

PMID- 18803692
TI  - Modulation of pro-survival and death-associated pathways under retinal
      ischemia/reperfusion: effects of NMDA receptor blockade.
AB  - Loss of retinal ganglion cells occurs in a variety of pathological conditions,
      including central retinal artery occlusion, diabetes and glaucoma. Using an
      experimental model of retinal ischemia induced by transiently raise the
      intraocular pressure (IOP), In this study, we report the original observation
      that ischemic retinal ganglion cells death is associated with the transient
      deactivation of the pro-survival kinase Akt and activation of GSK-3beta followed,
      during reperfusion, by a longer lasting, PI3K-dependent, activation of Akt and
      phosphorylation of GSK-3beta. Under these experimental conditions, retinal
      ischemia induced the expression of Bad, a pro-apoptotic protein, member of the
      Bcl-2 family. The detrimental effects yielded by the ischemic stimulus were
      minimized by intravitreal administration of the NMDA receptor antagonist, MK801,
      that reduced the expression of Bad and significantly increased Akt
      phosphorylation. In conclusion, our present results contribute to unravel the
      mechanisms underlying retinal damage by high IOP-induced transient ischemia in
      rat. In addition, these data implicate the pro-survival PI3K/Akt pathway and the
      observed reduced expression of Bad in the neuroprotection afforded by MK801.

PMID- 18803693
TI  - Amino acids involved in conformational dynamics and G protein coupling of an
      odorant receptor: targeting gain-of-function mutation.
AB  - Thousands of different odorants are recognized and discriminated by odorant
      receptors (ORs) in the guanine nucleotide-binding protein (G protein)-coupled
      seven-transmembrane receptor family. Odorant-bound ORs stimulate Gs-type G
      proteins, Galphaolf, which in turn activates cAMP-mediated signaling pathway in
      olfactory sensory neurons. To better understand the molecular basis for OR
      activation and G protein coupling, we analyzed the effects of a series of site
      directed mutations of mouse ORs, on function. Mutations of conserved amino acid
      residues in an intracellular loop or the C-terminus resulted in loss of activity
      without impairing ligand-binding activity, indicating that these residues are
      involved in Galphas/olf coupling. Moreover, mutation of the serine in KAFSTC, the
      OR-specific sequence motif, resulted in a dramatic increase in odorant
      responsiveness, suggesting that the motif is involved in a conformational change
      of the receptor that regulates G protein coupling efficiency. Our results provide
      insights into how ORs switch from an inactive to an active state, as well as
      where and how activated ORs interact with G proteins.

PMID- 18803694
TI  - Pathogenic missense MAPT mutations differentially modulate tau aggregation
      propensity at nucleation and extension steps.
AB  - Mutations in the MAPT gene encoding tau protein lead to neurofibrillary lesion
      formation, neurodegeneration, and cognitive decline associated with
      frontotemporal lobar degeneration. While some pathogenic mutations affect MAPT
      introns, resulting in abnormal splicing patterns, the majority occur in the tau
      coding sequence leading to single amino acid changes in tau primary structure.
      Depending on their location within the polypeptide chain, tau missense mutations
      have been reported to augment aggregation propensity. To determine the mechanisms
      underlying mutation-associated changes in aggregation behavior, the
      fibrillization of recombinant pathogenic mutants R5L, G272V, P301L, V337M, and
      R406W prepared in a full-length four-repeat human tau background was examined in
      vitro as a function of time and submicromolar tau concentrations using electron
      microscopy assay methods. Kinetic constants for nucleation and extension phases
      of aggregation were then estimated by direct measurement and mathematical
      simulation. Results indicated that the mutants differ from each other and from
      wild-type tau in their aggregation propensity. G272V and P301L mutations
      increased the rates of both filament nucleation and extension reactions, whereas
      R5L and V337M increased only the nucleation phase. R406W did not differ from wild
      type in any kinetic parameter. The results show that missense mutations can
      directly promote tau filament formation at different stages of the aggregation
      pathway.

PMID- 18803696
TI  - Radical scavenging-linked antioxidant activity of ethanolic extracts of diverse
      types of extra virgin olive oils.
AB  - The present study evaluated the radical scavenging-linked antioxidant activity of
      hexane/80% ethanol extracts from several types of extra virgin olive oils (EVOOs)
      derived from varieties arbequina, hojiblanca, picual, their blends, and pure
      olive oil (POO). The antioxidant potential of the olive oil extracts was assessed
      by radical scavenging assays using DPPH (2, 2-diphenyl-1-picrylhydrazyl), ABTS
      (2, 2'-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid), and hydroxyl radical,
      as well as hydrogen peroxide and superoxide anion inhibitory activities. Electron
      donating ability (EDA) using DPPH assay of 80% ethanol extracts from EVOOs,
      except arbequina oil, was significantly higher than POO. EDA was markedly higher
      in blended and picual EVOOs than the extracts from arbequina and hojiblanca EVOOs
      (P < 0.05). Similarly, ABTS radical scavenging activity of the extracts from the
      EVOOs was in order of picual EVOO > blended EVOO > hojiblanca EVOO >or= POO >or=
      arbequina EVOO. Further, the superoxide anion scavenging activity of blended,
      picual, and arbequina EVOOs was significantly higher than that of hojiblanca EVOO
      and POO, which were barely detectable. Hydroxyl radical scavenging activity of
      arbequina and hojiblanca was higher than that of blended, picual EVOOs, and POO.
      In addition, hydrogen peroxide scavenging activity of the extracts from blended,
      arbequina, hojiblanca, picual EVOOs, and POO was 63.1 +/- 3.1%, 44.4 +/- 10.2%,
      52.0 +/- 2.7%, 71.8 +/- 2.5%, and 35.7 +/- 10.0%, respectively. Our results
      indicate that ethanol extracts of several EVOOs contained higher radical
      scavenging and antioxidant activity than the POO. This antioxidant potential is
      partly due to the phenolic compounds present in different olive oil grade and is
      influenced by cultivar type.

PMID- 18803695
TI  - Phosphorylation of GRK7 by PKA in cone photoreceptor cells is regulated by light.
AB  - The retina-specific G protein-coupled receptor kinases, GRK1 and GRK7, have been
      implicated in the shutoff of the photoresponse and adaptation to changing light
      conditions via rod and cone opsin phosphorylation. Recently, we have defined
      sites of phosphorylation by cAMP-dependent protein kinase (PKA) in the amino
      termini of both GRK1 and GRK7 in vitro. To determine the conditions under which
      GRK7 is phosphorylated in vivo, we have generated an antibody that recognizes
      GRK7 phosphorylated on Ser36, the PKA phosphorylation site. Using this phospho
      specific antibody, we have shown that GRK7 is phosphorylated in vivo and is
      located in the cone inner and outer segments of mammalian, amphibian and fish
      retinas. Using Xenopus laevis as a model, GRK7 is phosphorylated under dark
      adapted conditions, but becomes dephosphorylated when the animals are exposed to
      light. The conservation of phosphorylation at Ser36 in GRK7 in these different
      species (which span a 400 million-year evolutionary period), and its light
      dependent regulation, indicates that phosphorylation plays an important role in
      the function of GRK7. Our work demonstrates for the first time that cAMP can
      regulate proteins involved in the photoresponse in cones and introduces a novel
      mode of regulation for the retinal GRKs by PKA.

PMID- 18803697
TI  - Characterization of asparagus lignin by HPLC.
AB  - Lignin is the cell wall component most frequently associated with hardening. Its
      characterization and quantification are very important to understand the
      biochemical modifications related to the changes in texture of vegetables such as
      asparagus (Asparagus officinalis), in which this organoleptic attribute is a very
      important quality factor. In this study, asparagus lignin from the basal sections
      of fresh and stored spears was analyzed using 2 methods, the traditional (Klason
      lignin) and the recently developed derivatization, followed by reductive cleavage
      (DFRC) method. The latter is a simple and reproducible technique for lignin
      characterization based on a degradation procedure that produces analyzable
      monomers and dimers by cleaving alpha- and beta-aryl ethers in lignins. The
      primary monomers derived from DFRC degradation of lignins are essentially p
      coumaryl peracetate, coniferyl peracetate, and sinapyl peracetate. To evaluate
      the efficiency of the DFRC method, our investigations have been carried on
      distinct sample types, including wood (data not shown), straw, and asparagus
      samples. The results have confirmed that lignin composition is affected by plant
      nature. It has been found that whereas wood samples mostly contain coniferyl
      units, plant foods, such as straw and asparagus, contain both coniferyl and
      guaiacyl units.

PMID- 18803698
TI  - Calcium Uptake during Immersion of Strawberries in CaCl2 Solutions.
AB  - The present study studied calcium uptake in strawberries during immersion in
      CaCl(2) solutions by analyzing total calcium and cell-wall calcium contents and
      the relationships between cell-wall calcium content, pectin content, and the
      degree of pectin esterification, considering different temperatures and
      concentrations of the immersion solution. In addition, calcium uptake at
      different zones of the strawberries was studied. Calcium uptake increased
      significantly when the concentration of the immersion solution increased from 1%
      to 10% (v/v), and calcium uptake was higher at 38 degrees C at some immersion
      times, but there were no significant differences between 1 and 24 degrees C. Most
      of the calcium incorporated by the strawberries was retained in the alcohol
      insoluble solids and it may be related to calcium bounded to the cell wall.
      Calcium content did not change during immersion in CaCl(2) solution in the
      internal or in the central zones; however, it increased significantly in the
      external zone.

PMID- 18803699
TI  - Antibacterial compounds from Rose Bengal-sensitized photooxidation of beta
      caryophyllene.
AB  - The bactericidal activity of beta-caryophyllene photooxidized in acetonitrile was
      examined for 5 Gram-positive and 4 Gram-negative foodborne bacteria. The beta
      caryophyllene (5 x 10(-3) M) was photooxidized in acetonitrile containing Rose
      Bengal (6.25 x 10(-4) M) for 24 h under fluorescent light. The antimicrobial
      activities of samples were determined by the agar-disc diffusion method. Active
      compounds from the photooxidized beta-caryophyllene were isolated by silica gel
      open-column chromatography in conjunction with recyclic high-performance liquid
      chromatography (HPLC), and were identified by infrared spectroscopy, mass
      spectrometry, and nuclear magnetic resonance spectroscopy. The antimicrobial
      activity of the photooxidized beta-caryophyllene was strongly enhanced against
      Streptococcus aureus and Vibrio parahaemolyticus, relative to that of beta
      caryophyllene, but was weakly enhanced against other tested bacteria. The
      photooxidized beta-caryophyllene contained 3 active compounds specific for these
      2 bacteria, and the compounds were identified as 5-alpha-hydroxycaryophylla
      4(12),8(13)-diene, 5-alpha-hydroxycaryophylla-3(4),8(13)-diene, and 5-beta
      hydroxycaryophylla-3(4),8(13)-diene. The efficacies of these compounds were
      similar, but the efficacy of 5-beta-hydroxycaryophylla-3(4),8(13)-diene was
      slightly higher than that of the other 2 compounds. The results suggest that the
      antibacterial activities of beta-caryophyllene for S. aureus and V.
      parahaemolyticus could be enhanced by dye-sensitized photooxidation, and the
      photooxidized beta-caryophyllene and the isolated individual compounds could be
      useful antimicrobial agents to control the growth of S. aureus and V.
      parahaemolyticus in certain food systems.

PMID- 18803700
TI  - Changes in the radical-scavenging activity of bitter gourd (Momordica charantia
      L.) during freezing and frozen storage with or without blanching.
AB  - The effects of blanching, freezing, and frozen storage on the retention of
      radical-scavenging activity (RSA), total phenolics, and ascorbic acid in bitter
      gourd were investigated. Blanching of sliced bitter gourd resulted in
      considerable losses of RSA and total phenolics, and most extensively, of ascorbic
      acid. In the subsequent frozen storage at -18 degrees C, RSA and total phenolic
      content of unblanched and blanched bitter gourd underwent little change for 90 d
      then gradually declined, but at -40 degrees C, they practically remained
      unchanged throughout the entire storage period. On the contrary, ascorbic acid
      content of both unblanched and blanched bitter gourd decreased abruptly at the
      early stage in frozen storage. The results show that blanching of bitter gourd
      improves the retention of RSA and total phenolics during subsequent frozen
      storage but markedly aggravated loss of ascorbic acid. Finally, it is to be noted
      that RSA, total phenolics, and ascorbic acid originally contained in the raw
      bitter gourd were overall best retained by quick freezing followed by frozen
      storage at -40 degrees C without preceding blanching.

PMID- 18803701
TI  - Effects of riboflavin photosensitization on the changes of isoflavones in
      soymilk.
AB  - Effects of riboflavin photosensitization on the distribution of isoflavones in
      commercially available soymilk were analyzed using high-performance liquid
      chromatography (HPLC). Total isoflavones (TI) in soymilk with riboflavin (1000
      ppm, w/v) under light were significantly different from those stored in the dark
      for 24 h (P < 0.05), while TI in samples with 0 and 1000 ppm added riboflavin
      were not significant from each other in dark conditions (P > 0.05). To test the
      effects of the concentration of riboflavin on TI, soymilk was mixed with
      riboflavin to make 0, 100, 250, and 500 ppm (w/v) and stored under light at 25
      degrees C for 24 h. TI in soymilk with 100 ppm riboflavin under light
      significantly decreased by 13.5% for 24 h (P < 0.05) compared to control samples
      and were not significantly different from those with 250 or 500 ppm samples (P >
      0.05). Daidzin and genistin were predominant isoflavones in soymilk, and the rate
      of photo degradation of genistin was higher than that of daidzin for 24 h in
      soymilk under riboflavin photosensitization.

PMID- 18803702
TI  - Cosupplementation of dietary calcium and conjugated linoleic acid (CLA) improves
      bone mass in mice.
AB  - Conjugated linoleic acid (CLA) has shown a variety of biologically beneficial
      effects, such as anticancer, antiatherosclerosis, antidiabetic, immunomodulating,
      and antiobesity effects. Its effects on reduction of body fat occur with
      enhancement of lean body mass and body ash; the effects of CLA on bone mass are
      inconsistent in mice and human studies. We hypothesized that the inconsistency of
      CLA's effect on ash may be linked to interaction between CLA and dietary calcium
      levels. We reanalyzed our previous studies, which used mice fed 0.5% CLA
      containing diet with regular calcium content (0.5%) or enhanced calcium level
      (0.66%). Extra calcium in the diet improved CLA's effects on bone mass,
      particularly in male mice (P= 0.0194); without extra dietary calcium there was no
      effect of CLA on bone mass. This finding may help improve the efficacy of CLA to
      be used as a dietary supplement to be used as part of an osteoporosis prevention
      strategy. Further studies are needed to confirm this observation.

PMID- 18803703
TI  - Antioxidant effects of flavonoids used as food additives (purple corn color,
      enzymatically modified isoquercitrin, and isoquercitrin) on liver carcinogenesis
      in a rat medium-term bioassay.
AB  - To clarify the effects of purple corn color, enzymatically modified isoquercitrin
      (EMIQ), and isoquercitrin (IQ), registered as natural food additives in Japan, on
      liver carcinogenesis in vivo, a medium-term bioassay was employed. A total of 100
      male F344 rats were divided into 5 groups; groups 1 to 4 were given a single
      intraperitoneal injection of diethylnitrosamine (200 mg/kg b.w.) on day 1. From
      weeks 2 to 8, they were administered basal diet purple corn color, EMIQ, or IQ as
      containing test chemicals at doses of 1.0% (groups 1 and 5), 0.1% (group 2),
      0.01% (group 3), or 0% (group 4) (experiments 1, 4, and 5). All rats were
      subjected to two-thirds partial hepatectomy at week 3 and were sacrificed at week
      8. Purple corn color exerted no significant modifying effects on GST-P positive
      foci, preneoplastic foci, development in the liver. However, serum of rats
      treated with purple corn color provided evidence of antioxidant power
      significantly by potential antioxidant (PAO) test in vivo (experiment 2). And
      microarray analyses showed purple corn color to induce RNA expression such as
      P450 (cytochrome) oxidoreductase, phosphatidylinositol 3-kinase, and
      phospholipase A2 (experiment 3). Higher doses of EMIQ or IQ with strong
      antioxidant power in vivo by PAO test treated groups were correlated with smaller
      numbers of GST-P positive foci, with Spearman's rank correlation coefficients of
      P= 0.002 and P= 0.049, respectively (experiments 4 and 5). Therefore, the tested
      food additives may be effective as antioxidants in vivo and have chemopreventive
      potential against liver preneoplastic lesion development.

PMID- 18803704
TI  - Concentrations of functional lipids in abraded fractions of hulless barley and
      effect of storage.
AB  - Hulless barley kernels were sequentially abraded to achieve 4%, 8%, 16%, 24%,
      32%, and 40% removal. Abraded fines, kernels, and ground kernels were stored at
      35 degrees C and 75% relative humidity for 3 wk. Stored samples were extracted
      and the levels of oil, free phytosterols, tocopherols (Ts), and tocotrienols
      (T3s) were analyzed and compared with freshly abraded fractions. The results
      revealed that oil, sterols, and Ts were concentrated in the outer layers,
      particularly in the germ layer. In whole kernels, homologues of both Ts and T3s
      showed the same ranking order in concentrations as alpha > gamma > beta > delta.
      The homologue composition of Ts remained the same but that of T3s changed across
      the kernel. The %T3 in total tocols increased in fractions with increasing
      endosperm tissue. Storage caused no change in oil and Ts but significant changes
      in sterols and T3s. The changes were differential among T3 isomers, with alpha-T3
      decreasing and delta-T3 increasing. The degradation of alpha-T3 was accelerated
      in fractions with more endosperm tissue. Grinding kernel samples before storage
      accelerated sterol degradation but had a limited effect on changes of T3s. A 2nd
      experiment using a different hulless barley line and ambient storage for 6 mo
      confirmed all the findings except that the changing trend for sterols was
      inconsistent. These results provide practical information to those who wish to
      produce a barley fraction enriched with a particular functional lipid and
      maintain stability of their products.

PMID- 18803705
TI  - Sorption isotherm and plasticization effect of moisture and plasticizers in pea
      starch film.
AB  - Pea starch films were produced with various plasticizers (glucose, fructose,
      mannose, sorbitol, and glycerol). Effects of plasticizer content (4.34 to 10.87
      mmol/g of dry starch) and storage relative humidity (RH) (11.3% to 75.4%) on
      moisture content (MC), tensile strength (TS), elongation (E), modulus of
      elasticity (EM), and water vapor permeability (WVP) were evaluated using response
      surface methodology. MC was influenced strongly by RH. Glycerol-plasticized films
      had the highest MC, indicating that water molecules played a more important role
      in plasticizing starch films. Monosaccharide-plasticized films and polyol
      plasticized films had similar TS values. However, monosaccharide-plasticized
      films had higher E values and lower EM values than polyol-plasticized films,
      meaning monosaccharides had better efficiency in plasticizing starch films.
      Recrystallization happened in glucose- and sorbitol-plasticized films when they
      were stored in high RH. Sorption isotherm studies showed the similar adsorption
      and desorption profiles for all 3 monosaccharide-plasticized films and a
      hysteresis. The Flory-Huggius model fitted experimental data best for starch
      films, while the BET model fitted the data marginally.

PMID- 18803706
TI  - Microstructure of fat globules in whole milk after thermosonication treatment.
AB  - The structure of fat globules in whole milk was studied after heat and
      thermosonication treatments to observe what happens during these processes at the
      microscopic level using scanning electron microscopy. Raw whole milk was
      thermosonicated in an ultrasonic processor-Hielscher UP400S (400 W, 24 kHz, 120
      microm amplitude), using a 22-mm probe at 63 degrees C for 30 min. Heat treatment
      involved heating the milk at 63 degrees C for 30 min. Color and fat content were
      measured to correlate the images with analytical measurements. The results showed
      that the surface of the fat globule was completely roughened after
      thermosonication. Ultrasound waves were responsible for disintegrating the milk
      fat globule membrane (MFGM) by releasing the triacylglycerols. Furthermore, the
      overall structure of milk after sonication showed smaller fat globules (smaller
      than 1 microm) and a granular surface. This was due to the interaction between
      the disrupted MFGM and some casein micelles. Minor changes in the aspect of the
      globules between thermal and raw milks were detected. Color measurements showed
      higher L* values for sonicated samples. Sonicated milk was whiter (92.37 +/-
      0.20) and generally showed a better degree of luminosity and homogenization
      compared to thermal treated milk (88.25 +/- 0.67) and raw milk (87.82 +/- 0.18).
      Fat content analysis yielded a higher value after sonication (4.24%) compared to
      untreated raw milk (4.04%) because fat extraction is more efficient after
      sonication. The advantages of thermosonicated milk are that it can be pasteurized
      and homogenized in just 1 step, it can be produced with important cost savings,
      and it has better characteristics, making thermosonication a potential processing
      method for milk and most other dairy products.

PMID- 18803707
TI  - Determination of sodium chloride in pork meat by computed tomography at different
      voltages.
AB  - Ground pork samples simulating the widely different chemical composition of hams
      during dry-cured ham production were produced and scanned by x-ray computed
      tomography (CT). Chemical composition accounted for most of the variation in CT
      values (97%). Tube voltage (80, 110, and 130 kV) affected CT value and the effect
      varied between different types of tissue. Sodium chloride (NaCl) was predicted in
      the ground samples with average prediction errors (RMSEP) as low as 0.2% to 1.0%
      NaCl. NaCl was also predicted in small samples of raw to dry-cured ham. When dry
      and fat ham samples were left out of the models, NaCl was predicted with a high
      precision (RMSEP 0.2% to 0.4% NaCl, R(2) > 0.99). CT can be used as a valuable,
      nondestructive tool to analyze distribution of and quantify NaCl in ham during
      dry-curing.

PMID- 18803708
TI  - Aroma precursors and methylpyrazines in underfermented cocoa beans induced by
      endogenous carboxypeptidase.
AB  - Cocoa-specific aroma precursors and methylpyrazines in underfermented cocoa beans
      obtained from fermentation induced by indigenous carboxypeptidase have been
      investigated. Fermentation conditions and cocoa bean components were analyzed
      during 0 to 3 d of fermentation. Underfermented cocoa beans were characterized as
      having hydrophilic peptides and free hydrophobic amino acids much higher than
      unfermented ones. These 2 key components of cocoa aroma precursors may be
      produced from the breakdown of proteins and polypeptides by endogenous
      carboxypeptidase during the fermentation process. The enzyme was activated during
      fermentation. Polypeptides of 47, 31, and 19 kDa were observed in the samples
      throughout the 3-d fermentation period; however, only the first 2 polypeptides
      were remarkably reduced during fermentation. Since the 1st day of fermentation,
      underfermented cocoa beans contained methylpyrazines, a dominant group of cocoa
      specific aroma. This might be due to microbial activities during fermentation,
      observed through a decrease of pH value and an increase of temperature of cocoa
      beans. The concentration of tetramethylpyrazines was significantly increased
      during the 3 d of fermentation. This may increase the cocoa-specific flavor to
      the beans.

PMID- 18803709
TI  - Lipid-lowering and LDL-oxidation inhibitory effects of aqueous extract of
      freshwater clam (Corbicula fluminea)--using tilapia as an animal model.
AB  - A previous study has demonstrated that tilapia able to exhibit hyperlipidemia and
      hypercholesterolemia is a good model for the evaluation of beneficial effects of
      nutraceuticals. In this study, tilapia were used to evaluate the in vitro and in
      vivo effects of a hot water extract (FC-HW) of freshwater clam (Corbicula
      fluminea). FC-HW prolonged the lag phase of Cu(2+)-induced human and tilapia LDL
      oxidation. The prolongation of the lag phase was concentration-dependent in human
      (r(2)= 0.94) and tilapia LDL (r(2)= 0.98). The antioxidative potential of FC-HW
      was 0.33% (on a weight basis) of Trolox, a positive control. Male tilapia (n= 24)
      were randomly divided into 2 groups and separately fed for 60 d with an
      isocaloric also isoprotein diet containing 2% (w/w) FC-HW or a control diet. Body
      length and body mass were significantly higher in fish fed FC-HW than those of
      the control group (P < 0.05). Total triacylglycerol, cholesterol, and LDL-C in
      plasma of the FC-HW group were significantly lower (-89.9%, -61.8%, and -54.5%,
      respectively), while plasma total antioxidant capacity of the FC-HW group was
      higher and the lag phase in Cu(2+)-induced LDL oxidation was longer than those of
      the control group (P < 0.05). FC-HW demonstrated hypolipidemia and
      hypocholesterolemia effects and inhibited human LDL oxidation in vitro and
      tilapia LDL both in vitro and ex vivo, indicative that FC-HW can be a potential
      nutraceutical to reduce the risk factors of atherosclerosis.

PMID- 18803710
TI  - Hematological toxicity associated with tissue extract from poisonous fish
      Lagocephalus lagocephalus--influence on erythrocyte function in Wistar rats.
AB  - The puffer fish Lagocephalus lagocephalus represents serious public health
      problems in the world. The relative toxicity of each organ (liver and flesh) was
      determined by the relation dose-death time "mouse bioassay." The average liver
      toxicity of the puffer fish was the highest when compared with flesh giving 14.32
      and 10.88 MU/g, respectively. A mouse unit is the amount of toxin (extract of
      fish organ) that kills a 20 g male mouse in 30 min after intraperitoneal
      injection. One mouse unit is equivalent to 0.22 microg of TTX. For the rat
      bioassay tests, Wistar rats were daily i.p. injected, for 10 d, with extracts of
      liver (LT) or flesh (FT) (muscles + skin) of L. lagocephalus. Control rats
      received injection of NaCl (0.9%). During the experiment, a significant reduction
      in red blood cell number (RBC), hemoglobin (HGB) concentration, and hematocrit
      (HCT) was observed essentially after 10 d of treatment in the FT and LT-exposed
      groups. Consequently, treatment led to severe anemia and hemolytic action as
      indicated by a significant reduction in the total number of erythrocytes. In
      fact, our study revealed a significant increase in erythrocyte lipid peroxidation
      (LPO) in FT and LT groups compared with controls after experimental exposure. The
      flesh and liver tissue extracts also altered antioxidative enzymes activities:
      catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px).
      Histopathological alterations in the spleen occurred exclusively at the end of
      treatment. We marked also an increase in reticulo-endothelial cells, which led to
      remove damaged erythrocytes.

PMID- 18803711
TI  - Effects of processing methods on amaranth starch digestibility and predicted
      glycemic index.
AB  - Amaranth has attracted a great deal of interest in recent decades due to its
      valuable nutritional, functional, and agricultural characteristics. Amaranth
      seeds can be cooked, popped, roasted, flaked, or extruded for consumption. This
      study compared the in vitro starch digestibility of processed amaranth seeds to
      that of white bread. Raw seeds yielded rapidly digestible starch content (RDS) of
      30.7% db and predicted glycemic index (pGI) of 87.2, the lowest among the studied
      products. Cooked, extruded, and popped amaranth seeds had starch digestibility
      similar to that of white bread (92.4, 91.2, and 101.3, respectively), while
      flaked and roasted seeds generated a slightly increased glycemic response (106.0
      and 105.8, respectively). Cooking and extrusion did not alter the RDS contents of
      the seeds. No significant differences were observed among popped, flaked, and
      roasted RDS contents (38.0%, 46.3%, and 42.9%, respectively), which were all
      lower than RDS content of bread (51.1%). Amaranth seed is a high glycemic food
      most likely because of its small starch granule size, low resistant starch
      content (< 1%), and tendency to completely lose its crystalline and granular
      starch structure during those heat treatments.

PMID- 18803712
TI  - Natural honey modulates physiological glycemic response compared to simulated
      honey and D-glucose.
AB  - The present study is undertaken to find out the relative glycemic tolerance of
      natural honey compared with simulated honey and D-glucose using oral glucose
      tolerance tested up to 180 min. Twenty-six healthy human subjects with mean age
      of 28.6 +/- 9.3 y were randomly divided into 3 groups, that is, natural honey
      consumers (NHC; n= 13), simulated honey consumers (AHC; n= 6), and D-glucose
      consumers (DGC; n= 7). After recording fasting blood glucose, the participants
      consumed either natural honey or simulated honey or D-glucose (1g/kg body
      weight). Subsequently, additional plasma glucose levels (PGLs) were recorded at
      60, 120, and 180 min. At 60 min, DGC and AHC group members exhibited similar PGL
      elevation (that is, 52% and 47%, respectively) compared to NHC group with only
      20% increment. On the other hand, after 180 min, 20% decrease in PGL was observed
      in the DGC group compared to 9.75% reduction in the NHC group. These observations
      are primarily in line with earlier studies. Results analyzed by one-way analysis
      of variance (ANOVA) showed significant differences between all 3 tested groups
      with F-statistic (19.96) and P value (< 0.005). Coefficient of variation of the
      NHC, AHC, and DGC groups were 14.8%, 20.2%, and 27.5%, respectively. Posthoc
      tests showed that glucose response was significantly lower in the NHC group at
      all time points (P < 0.005) compared to the AHC and DGC groups. In conclusion,
      natural honey stabilizes physiological glycemic response with rebound recovery of
      PGL.

PMID- 18803713
TI  - Effect of soluble soybean protein hydrolysate-calcium complexes on calcium uptake
      by Caco-2 cells.
AB  - Soybean protein hydrolysates (SPHs) bind with calcium, forming soluble SPH
      calcium complexes via the carboxyl groups of glutamic and aspartic acid residues.
      However, their effect on calcium uptake is still unclear. In this study, Caco-2
      cells were used to estimate the effect of SPH-calcium complexes with different
      molecular weights on calcium uptake in vitro. The changes in intracellular
      calcium ion concentration were measured by Fura-2 loading and expressed in
      fluorescence intensity. SPH-calcium complexes could promote calcium uptake.
      Improved fluorescence intensity was significantly different in SPH-calcium
      complexes (10 to 30 kDa), SPH-calcium complexes (3 to 10 kDa), and SPH-calcium
      complexes (1 to 3 kDa). The maximum levels of relative fluorescence intensity
      (18.3) occurred with SPH-calcium complexes (10 to 30 kDa). The effect of SPH
      calcium complexes (10 to 30 kDa) on Ca(2+) increase was determined to be
      concentration dependent in the range of 0.5 to 4 mg/mL. Our results indicate that
      soybean protein itself might be responsible for promoting calcium absorption.

PMID- 18803714
TI  - Antioxidative and anti-inflammatory protection of oleanolic acid and ursolic acid
      in PC12 cells.
AB  - PC12 cells were used to examine the in vitro antioxidative and anti-inflammatory
      effects of oleanolic acid (OA) and ursolic acid (UA). PC12 cells were pretreated
      with OA or UA at 20 and 40 microM and followed by exposure of hydrogen peroxide
      (H(2)O(2)) or 1-methyl-4-phenylpyridinium ion (MPP(+)) to induce cell injury.
      Results showed that H(2)O(2)- or MPP(+)-treatment significantly decreased cell
      viability and increased lactate dehydrogenase (LDH) release (P < 0.05). The
      pretreatment from OA or UA significantly and concentration-dependently reduced
      subsequent H(2)O(2)- or MPP(+)-induced cell death and LDH release (P < 0.05).
      Either H(2)O(2)- or MPP(+)-treatment significantly increased malonyldialdehyde
      (MDA) formation, decreased glutathione (GSH) content, and diminished glutathione
      peroxidase (GPX), catalase, and superoxide dismutase (SOD) activities (P < 0.05).
      The pretreatment from OA or UA significantly retained GSH, and reversed H(2)O(2)-
      and MPP(+)-induced impairment in catalase and SOD activities (P < 0.05), and
      decreased MDA formation (P < 0.05). Either H(2)O(2)- or MPP(+)-treatment
      significantly elevated interleukin-6 (IL-6) and tumor necrosis factor (TNF)-alpha
      levels (P < 0.05). The pretreatments from OA or UA significantly attenuated
      subsequent H(2)O(2)- or MPP(+)-induced release of IL-6 and TNF-alpha (P < 0.05).
      Based on the observed antioxidative and anti-inflammatory activities from OA and
      UA, these 2 compounds were potent agents against neurodegenerative disorder.

PMID- 18803715
TI  - Ethanolic extracts of Antrodia cinnamomea mycelia fermented at varied times and
      scales have differential effects on hepatoma cells and normal primary
      hepatocytes.
AB  - Mycelia of Antrodia cinnamomea (AC), an edible fungus native to Taiwan, were
      produced by submerged fermentation with various fermentation times in 250 mL, 5
      and 500 L fermentors and were evaluated for the effect of fermentation products
      on the viabilities of Hep3B and HepG2 hepatoma cells and normal primary rat
      hepatocytes. The results showed that the ethanolic extracts of AC mycelia (from
      250 mL fermentation for 8 wk and 5 and 500 L fermentations for 4 wk) possessed
      high antihepatoma activity. The IC(50) of ethanolic extract of AC mycelia
      fermented for 8 wk in a 250 mL fermentor against Hep3B and HepG2 cells were 82.9
      and 54.2 microg/mL, respectively. Furthermore, the IC(50) for Hep3B and HepG2,
      treated with ethanolic extract of AC mycelia fermented for 4 wk in the 5 L
      fermentor were 48.7 and 3.8 microg/mL, respectively. Those treated with ethanolic
      extract of AC mycelia fermented for 4 wk in the 500 L fermentor were 36.9 and 3.1
      microg/mL, respectively. No adverse effects of all samples on normal primary rat
      hepatocytes were observed.

PMID- 18803716
TI  - Antimicrobial efficacy of citron essential oil on spoilage and pathogenic
      microorganisms in fruit-based salads.
AB  - The aim of this study was the evaluation of the effects of pure citral and citron
      essential oil on microbial spoilage and growth and survival of pathogenic
      microorganisms during storage. They were added in the syrup of industrial ready
      to-eat fruit salads stored at 9 degrees C. Both citral (25 to 125 ppm) and citron
      essential oil (300, 600, 900 ppm) were able to prolong the microbial shelf life
      of the fruit-based salads. The essential oil gave excellent results, avoiding the
      undesirable effects attributable to the cytotoxicity of citral. Citron essential
      oil doubled the time needed for the wild microflora to reach concentrations able
      to produce a perceivable spoilage in condition of thermal abuse (9 degrees C).
      The same essential oil had reduced effects on the survival of Gram-negative
      species Salmonella Enteritidis and Escherichia coli, but showed a strong
      inhibition toward the Gram-positive pathogen Listeria monocytogenes.

PMID- 18803717
TI  - Resistance of nutrient-deprived Listeria monocytogenes 10403S and a DeltasigB
      mutant to chemical stresses in the presence or absence of oxygen.
AB  - Nutrient-deprived Listeria monocytogenes have increased resistance to processing
      control measures. Heat-stressed L. monocytogenes cells produce higher counts
      under anaerobic conditions and SigB reportedly contributes to the survival of
      environmentally stressed Gram-positive bacteria. In this study, a wild type (wt)
      strain, L. monocytogenes 10403S, and a DeltasigB mutant, FSLA1-254, were stressed
      by starvation in phosphate buffered saline coupled with exposure to chemicals
      with/without oxygen. In the absence of chemicals, the mutant survived starvation
      almost as well as the wt, suggesting that the starvation survival response (SSR)
      in L. monocytogenes was SigB-independent. Conversely, in the presence of chemical
      stresses the SSR results differed depending on the chemical used. In the presence
      of sodium chloride (SC), both strains were able to express an SSR under aerobic
      conditions but not under anaerobic conditions. However, in the presence of sodium
      propionate (SP), the mutant yielded counts that were 2 log CFU/mL lower than the
      controls and their aerobic counterparts. In the presence of sodium lactate (SL),
      the mutant yielded counts that were approximately 3 log CFU/mL lower than the wt
      under anaerobic conditions. Thus, for the chemical stress produced by SC, the SSR
      appeared to be SigB-independent. The SSR of L. monocytogenes appeared to be SigB
      dependent following exposure to SP or SL under anaerobic conditions. Following
      exposure to sodium diacetate or lauric acid, both strains were unable to express
      an SSR. No detectable CFUs were observed after 14 to 21 d under either aerobic or
      anaerobic incubation. Therefore, these 2 chemicals could be used in biocidal
      formulations against L. monocytogenes cells under aerobic or anaerobic
      conditions.

PMID- 18803718
TI  - Mathematically assessing the consequences of food terrorism scenarios.
AB  - We derive mathematical expressions for the mean number of casualties resulting
      from a deliberate release of a biological or chemical agent into a food supply
      chain. Our analysis first computes the amount of contaminated food as a function
      of the network topology and vessel sizes in the food processing plant. A
      probabilistic analysis, in which each potential consumer of contaminated food has
      his own random purchase time, infectious dose, and incubation period, determines
      the number of people who consume enough tainted food to get infected or poisoned
      before the attack is detected and food consumption is halted. These simple
      formulas can be used by the U.S. government and the food industry to develop a
      rough-cut prioritization of the threats from food terrorism, which would be a 1st
      step toward the allocation of appropriate prevention and mitigation resources.

PMID- 18803719
TI  - Effect of desiccation, starvation, heat, and cold stresses on the thermal
      resistance of Enterobacter sakazakii in rehydrated infant milk formula.
AB  - Enterobacter sakazakii is an opportunistic foodborne pathogen that has been
      isolated from powdered infant milk formula. This study determined the effect of
      desiccation, starvation, heat and cold stresses on the thermal inactivation of E.
      sakazakii in rehydrated infant milk formula (RIMF). Stressed cells were mixed
      with RIMF at 52, 54, 56, and 58 degrees C for various time periods. The D- and z
      values were determined by using linear regression analysis. D-values for
      unstressed E. sakazakii at 52, 54, 56, and 58 degrees C were 15.33, 4.53, 2, and
      0.53 min, respectively. Desiccation and heat stresses, but not starvation or cold
      stress, caused significant (P < 0.05) reduction in D-values. The z-values of
      desiccated, starved, heat stressed, and cold stressed E. sakazakii were not
      significantly different from unstressed cells (4.22 degrees C). Thermal
      resistance of E. sakazakii in RIMF is affected by the environmental stresses;
      that is, desiccation and heat stresses that may surround the bacterium prior to
      the contamination of infant formula. The results of this study may be of use to
      regulatory agencies, infant milk producers, and infant caregivers to design
      heating processes to eliminate E. sakazakii that may be present in infant milk
      formula.

PMID- 18803720
TI  - Effect of addition of Versagel on microbial, chemical, and physical properties of
      low-fat yogurt.
AB  - The objective of this study was to examine the effect of Versagel on the growth
      and proteolytic activity of Streptococcus thermophilus 1275 and Lactobacillus
      delbrueckii ssp. bulgaricus 1368 and angiotensin-I converting enzyme inhibitory
      activity of the peptides generated thereby as well as on the physical properties
      of low-fat yogurt during a storage period of 28 d at 4 degrees C. Three different
      types of low-fat yogurts, YV0, YV1, and YV2, were prepared using Versagel as a
      fat replacer. The fermentation time of the low-fat yogurts containing Versagel
      was less than that of the control yogurt (YV0). The starter cultures maintained
      their viability (8.68 to 8.81 log CFU/g of S. thermophilus and 8.51 to 8.81 log
      CFU/g of L. delbrueckii ssp. bulgaricus) in all the yogurts throughout the
      storage period. There was some decrease in the pH of the yogurts during storage
      and an increase in the concentration of lactic acid. However, the proteolytic and
      ACE-inhibitory potential of the starter cultures was suppressed in the presence
      of Versagel. On the other hand, the addition of Versagel had a positive impact on
      the physical properties of the low-fat yogurt, namely, spontaneous whey
      separation, firmness, and pseudoplastic properties.

PMID- 18803721
TI  - Growth, proteolytic, and ACE-I activities of Lactobacillus delbrueckii ssp.
      bulgaricus and Streptococcus thermophilus and rheological properties of low-fat
      yogurt as influenced by the addition of Raftiline HP.
AB  - This study investigated the influence of incorporating Raftiline HP on the pH,
      growth, proteolytic, and angiotensin-I converting enzyme inhibitory activities
      and on spontaneous whey separation, firmness, and rheological properties of low
      fat yogurts during storage for 28 d at 4 degrees C. Three types of yogurts were
      prepared from skim milk containing 0% (YI0, control), 2% (YI2), and 3% (YI3)
      Raftiline HP, respectively. The incorporation of Raftiline HP improved the growth
      of starter organisms, particularly that of Lactobacillus delbrueckii ssp.
      bulgaricus, resulting in shorter fermentation time. There was a significant
      improvement in total proteolysis, which was highest in yogurt containing 3%
      Raftiline HP. The ACE inhibitory activity was maximal in YI3 compared to YI2 and
      YI0. Incorporation of Raftiline HP did not affect whey separation and firmness of
      the low-fat yogurts. All these products were more fluid like with distinct
      pseudoplastic properties and lesser ability to resist deformation upon applied
      shear.

PMID- 18803722
TI  - Comparative evaluation of yogurt and low-fat cheddar cheese as delivery media for
      probiotic Lactobacillus casei.
AB  - This study used Lactobacillus casei 334e, an erythromycin-resistant derivative of
      ATCC 334, as a model to evaluate viability and acid resistance of probiotic L.
      casei in low-fat Cheddar cheese and yogurt. Cheese and yogurt were made by
      standard methods and the probiotic L. casei adjunct was added at approximately
      10(7) CFU/g with the starter cultures. Low-fat cheese and yogurt samples were
      stored at 8 and 2 degrees C, respectively, and numbers of the L. casei adjunct
      were periodically determined by plating on MRS agar that contained 5 microg/mL of
      erythromycin. L. casei 334e counts in cheese and yogurt remained at 10(7) CFU/g
      over 3 mo and 3 wk, respectively, indicating good survival in both products. Acid
      challenge studies in 8.7 mM phosphoric acid (pH 2) at 37 degrees C showed numbers
      of L. casei 334e in yogurt dropped from 10(7) CFU/g to less than 10(1) CFU/g
      after 30 min, while counts in cheese samples dropped from 10(7) CFU/g to about
      10(5) after 30 min, and remained near 10(4) CFU/g after 120 min. As a whole,
      these data showed that low-fat Cheddar cheese is a viable delivery food for
      probiotic L. casei because it allowed for good survival during storage and helped
      protect cells against the very low pH that will be encountered during stomach
      transit.

PMID- 18803723
TI  - Antibacterial activity against E. coli O157:H7, physical properties, and storage
      stability of novel carvacrol-containing edible tomato films.
AB  - Edible films containing plant antimicrobials are gaining importance as potential
      treatment to extend product shelf life and reduce risk of pathogen growth on
      contaminated food surfaces. The main objective of the present study was to
      evaluate the antimicrobial activities, storage stabilities, and physical-chemical
      mechanica1 properties of novel edible films made from tomatoes containing
      carvacrol, the main constituent of oregano oil. The antimicrobial activities
      against E. coli O157:H7 and the stability of carvacrol were evaluated during the
      preparation and storage of tomato-based films made by 2 different casting
      methods, continuous casting and batch casting. Antimicrobial assays of tomato
      films indicated that optimum antimicrobial effects occurred with carvacrol levels
      of approximately 0.75% added to tomato purees before film preparation. HPLC
      analysis of the films indicated that the carvacrol concentrations and
      bactericidal effect of the films remained unchanged over the storage period of up
      to 98 d at 5 and 25 degrees C. Carvacrol addition to the tomato puree used to
      prepare the films increased water vapor permeability of tomato films. The
      continuous method for casting of the films appears more suitable for large-scale
      use than the batch method. This 1st report on tomato-based edible antimicrobial
      tomato films suggests that these films have the potential to prevent adverse
      effects of contaminated food and promote human health associated with the
      consumption of tomatoes.

PMID- 18803724
TI  - Properties of novel hydroxypropyl methylcellulose films containing chitosan
      nanoparticles.
AB  - In this study, chitosan nanoparticles were prepared and incorporated in
      hydroxypropyl methylcellulose (HPMC) films under different conditions. Mechanical
      properties, water vapor and oxygen permeability, water solubility, and scanning
      and transmission electron microscopy (SEM and TEM) results were analyzed.
      Incorporation of chitosan nanoparticles in the films improved their mechanical
      properties significantly, while also improving film barrier properties
      significantly. The chitosan poly(methacrylic acid) (CS-PMAA) nanoparticles tend
      to occupy the empty spaces in the pores of the HPMC matrix, inducing the collapse
      of the pores and thereby improving film tensile and barrier properties. This
      study is the first to investigate the use of nanoparticles for the purpose of
      strengthening HPMC films.

PMID- 18803725
TI  - Innovative uses of near-infrared spectroscopy in food processing.
AB  - Near-infrared spectroscopy (NIRS) has experienced widespread use as an analytical
      tool in the last 3 decades. Researchers today are exploring ways of applying NIRS
      that expand beyond compositional analyses into process control. Processes such as
      meat tenderness evaluation, curd cutting, and dough mixing have traditionally
      been controlled by highly skilled master craftsmen; new NIRS research
      applications are demonstrating that these complex processes can be monitored and
      controlled in situ to produce consistent, high quality end products with online
      NIRS technology. Additionally, researchers also now have the potential ability to
      develop new nondestructive spectroscopic techniques to probe the underlying
      molecular evolution of these products during processing.

PMID- 18803726
TI  - Protection of the gastrointestinal tract epithelium against damage from low pH
      beverages.
AB  - Extensive consumption of low pH beverages such as citrus juices (pHs 2.3 to 4.3),
      alcoholic beverages (pHs 2.7 to 4.5), and soft drinks (pHs 2.3 to 4.2) has raised
      the question of whether exposure of the gastrointestinal (GI) tract to acidic
      beverages will cause damage to the epithelial lining. To evaluate the potential
      effects of low pH beverages on the GI tract epithelium, a detailed examination of
      the literature was undertaken. In some animal models, there is evidence of damage
      to GI epithelial cells following exposure to low pH beverages; however, in these
      studies there is no definitive relationship between acidity and the amount or
      severity of damage. Results from several other studies, conducted in both animals
      and humans, indicate a lack of adverse effects on epithelial cells. Furthermore,
      there is no evidence that damage is irreversible. Permanent damage from routine
      exposure to acidic beverages in humans would not be expected because of repair
      mechanisms that are available to maintain a healthy epithelium. Additionally,
      numerous physical, chemical, and biological mechanisms are in place to prevent
      damage to the epithelial cells. Finally, the safe history of consumption of low
      pH beverages, including various fruit juices, supports the conclusion that low pH
      beverage ingestion does not cause damage to the GI epithelium.

PMID- 18803727
TI  - Effect of freezing time on the quality of Indian mackerel (Rastrelliger
      kanagurta) during frozen storage.
AB  - The present study aims to find the effect of freezing methods on the quality of
      mackerel (Rastrelliger kanagurta) in commercial plate and air blast freezers
      during freezing and subsequent frozen storage (-18 degrees C). Total time for
      freezing was significantly different (P < 0.05) between the plate and air blast
      freezers (90 and 220 min, respectively). This difference in the freezing time
      could be attributed to the varied quality of the 2 samples. Upon freezing, the
      moisture content decreased in air blast frozen samples compared to plate freezer
      where protein content decreased in both the samples. Upon freezing and during
      frozen storage, lipid oxidation products (peroxide value, thiobarbutiric acid
      value, and free fatty acid value) and volatile bases (total volatile base
      nitrogen and trimethyl amine nitrogen) showed an increasing trend in both the
      samples with values slightly higher in air blast frozen samples compared to plate
      frozen samples. The total plate counts showed a significantly (P < 0.05)
      decreasing trend in both the samples. K value did not show any significant (P <
      0.05) difference between the samples where as the histamine formation was
      significantly (P < 0.05) increased in air blast frozen samples compared to plate
      frozen samples. The taste and overall acceptability was significantly different
      (P < 0.05) in plate frozen samples compared to air blast frozen samples on 3rd
      month. Both samples were in acceptable condition up to 3 mo but the plate frozen
      samples quality was slightly better than the air blast frozen samples.

PMID- 18803728
TI  - Acceptability of micronutrient fortified school meals by schoolchildren in rural
      Himalayan villages of India.
AB  - This cross-sectional randomized controlled study assessed the social
      acceptability of micronutrient fortified cooked lunch meals by schoolchildren in
      rural Himalayan villages of India, in a program where the cooking and the
      micronutrient fortification were done at school. Subjects were randomly assigned
      to treatment (91) and control (90) groups. The treatment group consumed a weighed
      amount of cooked lunch meals fortified with locally produced multi-micronutrient
      premix and the control group consumed a weighed amount of the same meals but
      without added micronutrient premix. After having eaten, subjects were asked to
      rate, on a 3-point Likert scale using "smiley" faces, the pleasantness of smell,
      taste, and overall satisfaction with the food. The mean age of study children was
      7.96 +/- 1.64 y and 48.6% were males. The average amounts of food consumed by the
      treatment and control groups were 345 +/- 114 and 360 +/- 102.4 g, respectively.
      Addition of the multi-micronutrient premix to school meals did not significantly
      affect the mean amount of food consumed by the schoolchildren (P > 0.05;
      independent sample t-test). No significant differences were seen between
      treatment and control groups in terms of ratings for taste, smell, and the
      general acceptance of the micronutrient fortified or the unfortified school
      meals. In conclusion, the addition of a multiple micronutrient premix to school
      meals was well liked by schoolchildren and did not adversely affect their food
      consumption.

PMID- 18803729
TI  - Production and shelf stability of multiple-fortified quick-cooking rice as a
      complementary food.
AB  - Rice-based complementary foods normally contain inadequate amounts of several
      micronutrients, such as iron, calcium, and zinc. This study aimed at improving
      the quality of commercially produced rice-based complementary foods. The analysis
      centered on identifying a rice-based complementary food that is safe, stable,
      sensory acceptable, and economical in terms of fortificants (iron, calcium, zinc,
      thiamine, folate) and effectively packaged for industrial production and
      distribution. Product colors were mostly in green-yellow tone and slightly
      changed to more yellow during storage. Sensory acceptability was affected by
      changes in odor and rancidity but not in color. Rancidity scores were low in
      aluminum foil laminated plastic bags (ALU). Lipid oxidation significantly
      increased during storage, but at a slower rate when sodium citrate and ALU were
      used. Color differences of raw products were detected but not in the cooked ones.
      Mineral and vitamin losses during processing were 2% to 11% and 20% to 30%,
      respectively, but no losses were found during storage. FeSO(4)+ NaFeEDTA added
      with sodium citrate resulted in the most acceptable product for all packagings.
      The multiple-fortified quick-cooking rice (MFQCR) developed from this study could
      be a potentially useful tool for combating micronutrient deficiencies among
      infants and young children in the countries where rice is the staple food.

PMID- 18803730
TI  - Retention of quality and nutritional value of 13 fresh-cut vegetables treated
      with low-dose radiation.
AB  - Improving the microbial safety while maintaining quality of fresh fruits and
      vegetables will increase consumer confidence in fresh produce. This study was
      conducted to investigate the effects of irradiation at 1 kGy, a dose that
      potentially inactivates E. coli O157:H7 by 5 logs, on the quality of 13 common
      fresh-cut vegetables: iceberg, romaine, green and red leaf lettuce, spinach,
      tomato, cilantro, parsley, green onion, carrot, broccoli, red cabbage, and
      celery. The results showed that the appearance of irradiated samples was similar
      to the nonirradiated ones except that irradiated carrots, celery, cilantro, and
      green onions had higher appearance scores than corresponding nonirradiated
      vegetables. There was no difference in the instrumental texture between
      irradiated samples and nonirradiated ones. The aroma of several irradiated
      vegetables was significantly better than controls after 14-d storage, because
      these control samples decayed or senesced. The 1 kGy irradiation did not affect
      vitamin C content of most vegetables; however, irradiated green and red leaf
      lettuce had 24% to 53% lower vitamin C contents than the controls. Our results
      suggest that most fresh-cut fruits and vegetables tested can tolerate up to 1 kGy
      irradiation without significant losses in any of the quality attributes.

PMID- 18803731
TI  - Effect of grain type and toasting conditions of barrels on the concentration of
      the volatile substances released by the wood and on the sensory characteristics
      of Montepulciano d'Abruzzo.
AB  - We report the results of an aging trial of Montepulciano d'Abruzzo D.O.C. wine in
      commercially available oak barrels that differed in the type of wood grain (extra
      fine and fine) and cooperage toasting conditions: medium (EVM), light (EVL),
      medium for a shorter time (CM), and, finally, a single short-time pretoasting
      stage at high temperature (ExpT). The chemical-physical composition, the volatile
      substances released by the wood, and the sensory characteristics of wines after 6
      and 12 mo of aging were monitored. The differences observed were mainly in the
      concentration of volatile substances and the olfactory characteristics of the
      wines. The volatile compounds that could distinguish among the wines were the cis
      isomer of beta-methyl-gamma-octalactone, the ratio between cis and trans
      octalactone, vanillin, cyclotene, maltol, 5-methyl guaiacol, and the furfuryl
      compounds. The concentration of cis octalactone was influenced by the type of
      grain of the wood, while the cis/trans octalactones ratio varied depending on the
      toasting conditions used in the production of the barrels (the highest
      concentration was in EVL). In particular, the length of time (EVM compared with
      CM) and the temperature (EVM compared with EVL) of the toasting process
      influenced the concentration of vanillin, furfuryl alcohols, cis octalactone, and
      5 methyl guaiacol. Among the olfactory descriptors, statistically significant
      differences were detected in the notes of caramel, toasty, spicy, green pepper,
      coconut, and wood.

PMID- 18803734
TI  - People with mental disabilities negotiating life in the risk society: a
      theoretical approach.
AB  - Risk assessment and risk management owing to the potential threat from people
      with serious mental disorders living in the local community have been given much
      attention in psychiatric and mental healthcare research. Research connected to
      risks associated with living in the community for people with mental disabilities
      has also been published. This paper focuses on the situation of people with
      mental health problems and disabilities from a quite different perspective. In
      the light of the societal change towards what has been named the 'risk society',
      the consequences for vulnerable groups, especially people with mental
      disabilities, are discussed. Furthermore, the purpose is to shed light on how
      structural factors, like the process of individualization and 'de-population' of
      societal institutions, are affecting the living conditions for people with mental
      disabilities - positively as well as negatively. The importance of trust in the
      risk society is highlighted, but also the important role that the local community
      might play in relation to people with mental disabilities. Finally, some
      potentialities and new roles that this development towards a risk society and
      increased individualization paradoxically can open up for people with mental
      disabilities are outlined.

PMID- 18803735
TI  - Risk profiles for non-adherence to antipsychotic medications.
AB  - Poor adherence to medications is common in individuals with schizophrenia, and
      can lead to relapse and re-hospitalization. This paper presents the findings of
      an Australian study of the factors affecting antipsychotic medication taking in
      individuals with schizophrenia. The Factors Influencing Neuroleptic Medication
      Taking Scale was used with a non-probability sample of mental health service
      users. Ethics approval was obtained from a university and a hospital ethics
      committee. Data were analysed using spss version 15. Most participants had
      insight into their illness and were aware of the stigma of mental illness. Around
      70% experienced annoying side effects, while nearly half admitted alcohol
      consumption. About one-fifth admitted they had missed taking medications during
      the previous week. Significant others played a variable role in medication
      taking. Over 80% were satisfied with their relationships with health
      professionals, but were less satisfied with access to these professionals,
      especially psychiatrists. Logistic regression analysis showed that age, impact of
      medication side effects, and access to psychiatrists were independent predictors
      of medication omission. It is argued that medication taking is a complex issue,
      which needs to be taken into consideration in health professional training and
      measures to promote adherence.

PMID- 18803736
TI  - Nurse staffing, bed numbers and the cost of acute psychiatric inpatient care in
      England.
AB  - The aim of this analysis was to describe the composition, variability and factors
      associated with nurse staffing costs in acute psychiatric inpatient care. Numbers
      of acute inpatient beds in England have fallen, creating an occupancy crisis.
      Numbers of acute inpatient nursing staff are linked to quality of care. Variance
      in staffing and beds has considerable resource implications, but little is known
      about how these costs are structured. The sample comprised survey data from 136
      wards in 26 NHS Trusts, matched with nationally available data on service levels,
      population and outcomes. The cost of providing acute inpatient care varied
      fivefold between different Trusts. This variation comprised of numbers of
      beds/population, numbers of nurses/beds and the proportion of nurses qualified.
      These variations were not fully accounted for by differing levels of social
      deprivation. Although service provision levels in London were higher, wide
      variation in costs existed in every region. Associations between nursing cost per
      bed and performance indicators were found. As investment in acute inpatient care
      varies widely, we need to know much more about the relationship of inputs to
      outputs, so that empirically based standard service levels can be defined.

PMID- 18803737
TI  - Applications of simulation technology in psychiatric mental health nursing
      education.
AB  - The purpose of this paper is to review the use of simulation in education across
      the health professionals, to describe the development and implementation of
      innovative simulation techniques for an undergraduate psychiatric mental-health
      nursing course, and to identify lessons learned and future directions for
      successful simulation experiences in psychiatric nursing.

PMID- 18803738
TI  - Reflections on the notion of post-natal depression following examination of the
      scoring pattern of women on the EPDS during pregnancy and in the post-natal
      period.
AB  - The scoring pattern of case-positive women on the Edinburgh Postnatal Depression
      Scale (EPDS) was explored over the antenatal and post-natal period. Individual
      analysis of EPDS scores over the antenatal and post-natal period revealed a
      picture of depressive symptom reporting inconsistent with the notion of a
      distinct and separate entity of post-natal depression. A fundamental assumption
      that post-natal depression has a typical pattern of comparatively higher post
      natal depressive symptomology may be illusory when individual symptom profiles
      are explored.

PMID- 18803739
TI  - The collaborative care practice model in the long-term care of individuals with
      bipolar disorder: a case study.
AB  - Effective therapies for the long-term care of individuals with bipolar disorder
      feature medication management and an interactional component between patients and
      care providers. In this paper, we discuss the effectiveness of applying a
      collaborative practice model to the long-term care of individuals with bipolar
      disorder who receive outpatient treatment. The model emphasizes that patients are
      co-managers of their illness and successful outcomes are enhanced within a
      supportive social environment. Key elements include joint patient-provider
      treatment planning and decision making. Several controlled trials have
      demonstrated that when the model is adopted, significant improvements in clinical
      and functional outcomes can be achieved. The paper concludes with a case study,
      which illustrates that the model can be successfully implemented in a clinical
      setting. Given that the clinical and research evidence demonstrates the
      effectiveness of the model, we suggest that advanced practice psychiatric nurses
      apply key elements of the collaborative practice model in their work with clients
      with bipolar disorder.

PMID- 18803740
TI  - Promoting positive risk management: evaluation of a risk management panel.
AB  - The purpose of this study was to evaluate whether a National Health Service Trust
      risk management panel (RMP) service was effective in promoting positive risk
      management by supporting mental health clinicians/teams in their management of
      people with mental health problems who presented with high risk of harm to
      themselves or to others. Fifteen mental health workers completed a questionnaire
      regarding their experience of the RMP. Content analysis revealed several themes.
      The majority of participants found the RMP helpful because of the support
      provided by shared case discussion and collective responsibility for risk
      management offered by the RMP. Medical records of the 23 individuals referred
      into the RMP were also examined. Trends in diagnoses, risks and RMP
      recommendations were identified. This study points to the importance of the
      organization's role alongside the individual clinician's in positive risk
      management and in supporting people with mental health problems using the
      recovery model. Improvements in developing a RMP are suggested.

PMID- 18803741
TI  - An evaluation of a Mental Health Act educational resource.
AB  - The Mental Health (Care and Treatment) (Scotland) Act 2003 was developed with the
      participation of patients and carers. This Act is fundamentally different from
      all previous versions of the Mental Health Acts in the UK because it is based on
      Millan's 10 principles. Its objective is to ensure that people with mental
      disorder receive effective care and treatment. It is crucial that all staff who
      deal with persons with mental disorder are familiar with the Act and incorporate
      it into practice. This depends on the effectiveness of educational resources in
      supporting staff to develop their practice. The project presented here was
      commissioned by the National Health Service Education for Scotland (NES) to
      evaluate the accessibility and use of the educational resources produced for all
      frontline staff in Scotland. The aim was to evaluate the educational resources
      produced by NES to prepare the frontline staff in relation to the Mental Health
      (Care and Treatment) (Scotland) Act 2003. Evaluation was conducted through a
      questionnaire survey, focus groups and individual interviews. The NES educational
      resource was effective in assisting professionals in implementing the complex and
      progressive requirements of the new Mental Health Act. The three formats reached
      a wide audience, and are an effective model for future initiatives.

PMID- 18803742
TI  - Introduction of a child and adolescent mental health link worker: education and
      health staff focus group findings.
AB  - Policy guidance suggests that outcomes for adolescents with mental health
      problems can be improved by secondary education services (SES) and child and
      adolescent mental health services (CAMHS) working more closely. This study
      reports on staff experiences of the introduction of a mental health link worker
      (MHLW). The findings of two focus groups are presented, conducted with staff from
      CAMHS and SES. These focus groups formed part of the overall wider evaluation of
      the MHLW role. The groups explored staff perceptions and experiences following
      the introduction of the MHLW, and elicited their views on the effectiveness of
      this innovative role. Qualitative methods were employed, and analysis was
      conducted using the principles of grounded theory and the constant comparative
      method. The findings revealed that the MHLW was well received by both groups,
      despite the identification of potential barriers. A number of key themes emerged,
      which included the ability of the link worker to improve communication and to
      encourage mutual understanding between services. The issues raised by these
      themes are discussed and recommendations are made for future practice and
      research.

PMID- 18803743
TI  - User involvement in mental health care: the role of nurses. A literature review.
AB  - This literature review was carried out to examine the effects of user involvement
      in shared decision-making processes and the methods/tools available to
      psychiatric nurses to measure and encourage user involvement. A systematic
      literature review was then used in this study. Many studies indicate that an
      increased involvement of service users leads to better care, better treatment
      compliance, improved health outcomes and higher levels of patient satisfaction.
      The tools and methods described are designed to measure the ability to
      participate, the process of implementation and the evaluation of healthcare
      services. An adequate instrument to measure user involvement will be necessary to
      underpin the positive effects. Although care providers have a statutory duty to
      help shape user involvement, and the tools required are available, care providers
      are still insufficiently inclined to take up this duty.

PMID- 18803744
TI  - Mental illness: diagnostic title or derogatory term? (Attitudes towards mental
      illness) Developing a learning resource for use within a clinical call centre. A
      systematic literature review on attitudes towards mental illness.
AB  - With one in three people likely to experience mental health problems during their
      lifetime, it is paradoxical that stigma and negative attitudes towards mental
      illness are so prevalent in the UK today. This systematic literature review was
      completed to investigate what the most common negative attitudes towards mental
      illness are, and the most common recommendations made to address them. The
      findings were used to inform teaching resources used in an National Health
      Service Direct call centre. Guidelines for undertaking a systematic review,
      produced by the Centre for Reviews and Dissemination, were used. Terms were set
      and a search of electronic databases and peer-reviewed academic journals was
      completed, from which 16 primary research papers (from the UK) were obtained and
      used. These were assessed, using evidence-based critical appraisal tools, to
      obtain data pertinent to the original question. This paper describes the process,
      including a detailed account of the methodologies employed to gather and analyse
      relevant data. Put into context, alongside key drivers (e.g. government papers),
      the findings are presented and discussed, along with underlying theories, where
      appropriate. Recommendations for professional practice are then presented.

PMID- 18803745
TI  - What a commentary is for and for whom it is for?

PMID- 18803746
TI  - Verbicide.

PMID- 18803751
TI  - Improving the efficiency of insemination with sex-sorted spermatozoa.
AB  - The sorting of X- and Y-chromosome-bearing spermatozoa by flow cytometry is
      nowadays one of the most apt assisted-reproduction technologies in livestock
      production. Potential economic and biological benefits, as well as those related
      to easier management of herds, have been reported arising out of the application
      of this technique, especially in cattle. Yet, the sex-sorting procedure induces
      damage to spermatozoa, affecting their function and fertilizing ability.
      Different species present varying degrees of susceptibility to damage from the
      sorting process and each has its own requirements for sex-sorted insemination
      procedures. Thus, several new protocols and strategies have been designed for the
      handling of sorted spermatozoa, with the main objective of optimizing their
      fertilizing ability and the consequent application of flow-cytometric sex-sorting
      technology. This article reviews current advances in this technology, pointing
      out the components to be improved before this technology may be widely applied in
      different domestic species.

PMID- 18803752
TI  - Sperm cryopreservation in brown bear (Ursus arctos): preliminary aspects.
AB  - The development of sperm cryopreservation procedures in brown bear is the basis
      for establishing a specific genetic resource bank aimed at the preservation of a
      Cantabric brown bear population, which is seriously threatened. Several issues
      complicate the development of these cryopreservation procedures: lack of previous
      specific studies, a high incidence of urospermia and spermagglutination observed
      in bear ejaculates. Moreover, the availability of individuals for research from
      these threatened populations is problematic. In the case of the Cantabric brown
      bear, we have used males from other populations, but of the same species, as
      surrogates, to carry out a direct extrapolation of the results. Urospermia--
      Moreover, 70% of the ejaculates are urine contaminated and spermagglutination
      have a detrimental effect on post-thawing cell quality recovery in this species.
      Considering the high value of these samples (autochthonous population with few
      individuals), a pre-selection of the ejaculates is not a viable alternative.
      Preventive methods reducing the mentioned detrimental effects need to be
      developed. On the basis of previous data, we can suppose that bear spermatozoa
      resist freezing injuries well. Nevertheless, because of the scarcity of this
      information, it is necessary to conduct further research on bear semen freezing
      under field conditions. Epidydimal spermatozoa can be important for genetic
      resource banking of threatened populations and thus specific cryobiological
      protocols need to be assayed. To date, 168 brown bear ejaculates have been frozen
      by the ITRA-ULE group at the University of Leon (Spain) in the development of
      methodologies for the preservation of brown bear sperm.

PMID- 18803753
TI  - Seminal plasma proteins and sperm resistance to stress.
AB  - The role of seminal plasma (SP) in mammalian sperm function remains largely a
      matter of speculation as both inhibitory and stimulating effects have been found.
      Specific components of SP, particularly proteins, are adsorbed onto the surface
      of ejaculated sperm as they pass through the male and female reproductive tracts.
      These sperm coating components seem to have the important function of maintaining
      the stability of the membrane up to the process of capacitation (decapacitation
      factors). Therefore, they must be removed, modified or masked before the
      spermatozoa undergo the acrosome reaction, an essential process for successful
      fertilization. It is well known that low temperatures alter the function of
      spermatozoa. Cold shock results in the destabilization of sperm membranes and
      impairment of sperm function, and it is also well known that ram spermatozoa are
      more sensitive to cold-shock stress than those of other species. The addition of
      SP proteins to spermatozoa before and/or after cooling is able to minimize
      cryoinjury effects. The major proteins in ram SP which are able to protect and
      repair the cold-shock damage to sperm contain fibronectin-II domains. The
      significance of this domain and the role of these proteins in sperm capacitation
      and gamete interaction are discussed.

PMID- 18803754
TI  - Embryonic stem cells in cattle.
AB  - Because of the potential use of embryonic stem cells (ESC), especially for
      genetic modifications, there is great interest in establishing domestic animals
      related ESCs. Unfortunately, despite considerable efforts, validated ESC lines in
      species other than mice and primates are yet to be isolated. In this paper, we
      will summarize the current knowledge on bovine ESCs in an attempt to understand
      why derivation of domestic animal ESC is still unsuccessful and we will discuss
      some promising future approaches.

PMID- 18803755
TI  - Relationships between milk production, ovarian function and fertility in high
      producing dairy herds in north-eastern Spain.
AB  - In the dairy industry worldwide, reproductive disorders are a major cause of
      economic losses and a challenge to scientists and technicians. In recent decades,
      declining fertility and increasing milk production have been widely reported in
      dairy cattle. In this article, the relationships between milk production, ovarian
      disorders and fertility in high-producing dairy herds are briefly described. We
      carried out a retrospective study of 23 204 lactations included in a reproductive
      control programme in north-eastern Spain, a geographical area experiencing both
      warm and cool conditions. The data were collected between 1991 and 2007 and refer
      to cows first inseminated or examined 45-80 days postpartum in five well-managed,
      commercial, Holstein-Friesian high-producing dairy herds. Ovarian disorders were
      classified as ovarian inactivity or hypofunction, cystic ovarian disease, sub
      oestrus or silent ovulation and sub-luteal function. Ovarian hypofunction and
      milk production increased throughout the study period and there was a decrease in
      the pregnancy rate to first artificial insemination (AI). Cows suffering ovarian
      hypofunction were efficiently treated using combined progestagen-prostaglandin
      treatments. The incidence of ovarian cysts showed little variation with time.
      Treatment of this syndrome may include different GnRH-based treatments or manual
      rupture. During the last 5 years, sub-oestrus was the predominant dysfunction
      (42.1%) compared with the cystic (6.3%) and ovarian hypofunction (12%) forms.
      Response of sub-oestrous cows to treatment with luteolitic agents was usually
      higher than 60%. Ovarian function and fertility were dramatically impaired during
      the warm period. However, during the later years of the study, the inclusion of
      fans and water sprinklers for the warm season appeared to overcome the seasonal
      effect on fertility.

PMID- 18803756
TI  - Consequences of in vitro culture conditions on embryo development and quality.
AB  - Despite major efforts directed at improving the yield of blastocysts from
      immature oocytes in vitro, the quality of such blastocysts continually lags
      behind that of blastocysts produced in vivo. These differences are manifested at
      the level of morphology, metabolism, gene expression and cryotolerance, and may
      have a knock-on effect further along the developmental axis. Evidence suggesting
      that in vitro culture conditions, while capable of producing blastocysts in
      relatively high numbers, are far from optimal with deficiencies being manifested
      in terms of abnormally large offspring. It is clear nowadays that modification of
      the post-fertilization culture environment in vitro can improve blastocyst
      quality to some extent.

PMID- 18803758
TI  - Retraction. Cardiovascular dysautonomia in Parkinson's disease and multiple
      system atrophy.

PMID- 18803759
TI  - Retraction: "The use of adhesion prevention membranes in abdominal surgery" by H.
      S. Tilney, S. Purkayastha, V. A. Constantinides, R. Morris, A. W. Darzi & P. P.
      Tekkis.

PMID- 18803760
TI  - Impaired CD4 and CD8 T cell phenotype and reduced chemokine secretion in recent
      onset type 1 diabetic children.
AB  - Although the role of the T cell-mediated autoimmune reaction in type 1 diabetes
      (T1D) is conclusive, studies including data from human circulating CD4(+) and
      CD8(+) lymphocytes subsets during the disease onset and posterior development are
      scarce. Further, chemokines and chemokine receptors are key players in the
      migration of pathogenic T cells into the islets of non-obese diabetic mice
      developing T1D, but few studies have investigated these markers in human T1D
      patients. We studied the expression of T helper 1 (Th1)- and Th2-associated
      chemokine receptors, and the two isoforms of CD45 leucocyte antigen on CD4(+) and
      CD8(+) lymphocytes from T1D and healthy children, as well as the secretion of
      chemokines in cell supernatants in peripheral blood mononuclear cells. Our
      results showed increased expression of CCR7 and CD45RA and reduced CD45RO on
      CD8(+) cells among recent-onset T1D patients. The percentages of CD4(+) cells
      expressing CXC chemokine receptor 3 (CXCR3), CXCR6 and CCR5, and the secretion of
      interferon-gamma-induced protein-10, monocyte chemoattractant protein-1,
      macrophage inflammatory protein (MIP)-1alpha and MIP-1beta was lower among
      diabetics. Low expression of Th1-associated receptors and secretion of
      chemokines, together with an increased amount of CD8(+) cells expressing CD45RA
      and CCR7 in T1D patients therefore might represent suboptimal Th function in T1D,
      leading to impaired T cytotoxic responses or alternatively reflect a selective
      recruitment of Th1 cells into the pancreas.

PMID- 18803761
TI  - Systemic humoral immunity to non-typeable Haemophilus influenzae.
AB  - Non-typeable Haemophilus influenzae (NTHi) is a major cause of respiratory but
      rarely systemic infection. The host defence to this bacterium has not been well
      defined in patients with chronic airway infection. The aim of this study was to
      assess the effect of humoral immunity in host defence to NTHi. Responses were
      measured in control and bronchiectasis subjects who had recurrent bronchial
      infection. Antibody and complement-mediated killing was assessed by incubating
      NTHi with serum and the role of the membrane-attack complex and
      classical/alternate pathways of complement activation measured. The effect of one
      strain to induce protective immunity against other strains was assessed. The
      effect of antibody on granulocyte intracellular killing of NTHi was also
      measured. The results showed that both healthy control subjects and
      bronchiectasis patients all had detectable antibody to NTHi of similar titre.
      Both groups demonstrated effective antibody/complement-mediated killing of
      different strains of NTHi. This killing was mediated through the membrane-attack
      complex and the classical pathway of complement activation. Immunization of
      rabbits with one strain of NTHi resulted in protection from other strains in
      vitro. Antibody activated granulocytes to kill intracellular bacteria. These
      findings may explain why NTHi rarely causes systemic disease in patients with
      chronic respiratory mucosal infection and emphasize the potential importance of
      cellular immunity against this bacterium.

PMID- 18803762
TI  - Mitogenic effect contributes to increased virulence of Streptococcus suis
      sequence type 7 to cause streptococcal toxic shock-like syndrome.
AB  - Streptococcus suis serotype 2 sequence type 7 strains emerged in 1996 and caused
      a streptococcal toxic shock-like syndrome in 1998 and 2005 in China. Evidence
      indicated that the virulence of S. suis sequence type 7 had increased, but the
      mechanism was unknown. The sequence type 7 strain SC84, isolated from a patient
      with streptococcal toxic shock-like syndrome during the Sichuan outbreak, and the
      sequence type 1 strain 31533, a typical highly pathogenic strain isolated from a
      diseased pig, were used in comparative studies. In this study we show the
      mechanisms underlying cytokine production differed between the two types of
      strains. The S. suis sequence type 7 strain SC84 possesses a stronger capacity to
      stimulate T cells, naive T cells and peripheral blood mononuclear cell
      proliferation than does S. suis sequence type 1 strain 31533. The T cell response
      to both strains was dependent upon the presence of antigen-presenting cells.
      Histo-incompatible antigen-presenting cells were sufficient to provide the
      accessory signals to naive T cell stimulated by the two strains, indicating that
      both sequence type 7 and 1 strains possess mitogens; however, the mitogenic
      effect was different. Therefore, we propose that the difference in the mitogenic
      effect of sequence type 7 strain SC84 compared with the sequence type 1 strain
      31533 of S. suis may be associated with the clinical, epidemiological and
      microbiological difference, where the ST 7 strains have a larger mitogenic
      effect.

PMID- 18803763
TI  - A dendritic cell-based tumour vaccine for lung cancer: full-length XAGE-1b
      protein-pulsed dendritic cells induce specific cytotoxic T lymphocytes in vitro.
AB  - XAGE-1b is regarded as one of the most immunogenic antigens and the most
      promising targets for lung adenocarcinoma immunotherapy. In this study, we sought
      to determine whether monocyte-derived dendritic cells (DCs) pulsed with purified
      full-length XAGE-1b could induce specific cytotoxic T lymphocytes (CTLs) against
      tumour cells from patients with non-small cell lung cancer (NSCLC) in vitro. XAGE
      1b mRNA expression was examined in primary cultures of lung cancer cells and
      normal lung epithelial cells established from fresh tissues surgically resected
      from 30 patients with NSCLC using reverse transcription-polymerase chain reaction
      (RT-PCR). XAGE-1b mRNA expression was observed in 11 of 18 (61.1%)
      adenocarcinomas and one of 12 (8.3%) lung cancers of other histological types (P
      = 0.015). The 246-base pairs XAGE-1b gene was inserted into a recombinant
      expression vector. Full-length XAGE-1b was then expressed in BL21 (DE3)
      Escherichia coli and purified by AKTA-fast performance liquid chromatography
      (FPLC). DCs generated from peripheral blood mononuclear cells were pulsed with
      XAGE-1b by incubation with the protein at an immature stage. The XAGE-1b-pulsed
      DCs induced CTLs following 14 days of co-culture. Finally, an adherent target
      detachment (ATD) assay was performed to test the cytotoxicity of the XAGE-1b
      specific CTLs against cancer cells and normal lung epithelial cells. The XAGE-1b
      specific CTLs had a stronger lytic effect on autologous XAGE-1b mRNA-positive
      cancer cells than on autologous XAGE-1b mRNA-negative cancer cells or allogenous
      XAGE-1b mRNA-positive cancer cells. The CTLs had no lytic activity against normal
      lung epithelial cells. These results can be used to develop simple and effective
      cancer/testis antigen-based immunotherapies for NSCLC.

PMID- 18803764
TI  - Immunoglobulin E antibodies from pancreatic cancer patients mediate antibody
      dependent cell-mediated cytotoxicity against pancreatic cancer cells.
AB  - In addition to allergy and parasitic infections, immunoglobulin E (IgE) has been
      shown recently to possess anti-viral and anti-cancer effects. We investigated
      serum levels of IgE, its low-affinity receptor, soluble CD23 (sCD23) in patients
      with pancreatic cancer and the effect of IgE against pancreatic cancer cells.
      Twelve patients were evaluated for pancreatic cancer by imaging and confirmed by
      biopsy. Fifteen healthy volunteers served as controls. Serum Igs (IgG, IgM, IgA,
      IgE) and sCD23 levels were determined (enzyme-linked immunosorbent assay,
      nephelometry) and the presence of cancer-specific IgE was assessed (fluorescence
      microscopy, Western blot). IgE anti-cancer activity was determined by antibody
      dependent cell-mediated cytotoxicity (ADCC). Serum levels of IgE and sCD23 were
      elevated significantly in patients with pancreatic cancer versus controls,
      whereas no differences were observed in other Ig isotypes (IgG, IgM, IgA). Flow
      cytometry and immunofluorescence microscopy demonstrated similar presence of IgG
      and IgE pancreatic cancer Igs. However, Western blot analysis indicated
      differences in IgG and IgE antigen-specific antibodies; IgE antibody recognized a
      50 kD protein. ADCC studies demonstrated that serum and purified IgE-mediated
      cytotoxicity against pancreatic cancer cells, effects which were reversed with
      anti-IgE neutralizing antibody and IgE depletion (immunoaffinity); greater
      cytotoxicity was observed in patient serum when compared with healthy controls.
      These data suggest that IgE and sCD23 may serve as useful biomarkers for patients
      with pancreatic cancer and may be important in the immune response to this
      disease in that IgE-directed therapy may help to direct treatment.

PMID- 18803766
TI  - Riding the right wave: would the real neural crest please stand up?

PMID- 18803767
TI  - The basis of bee-ing different: the role of gene silencing in plasticity.

PMID- 18803768
TI  - Networking networks.

PMID- 18803769
TI  - HomeoDB: a database of homeobox gene diversity.
AB  - The homeobox genes are a large and diverse group of genes, many of which play
      important roles in the embryonic development of animals. Comparative study of
      homeobox genes, both within and between species, requires an evolutionary-based
      classification. HomeoDB was designed and implemented as a manually curated
      database to collect and present homeobox genes in an evolutionarily structured
      way, allowing genes, gene families and gene classes to be compared between
      species more readily than was possible previously. In its first release, HomeoDB
      includes all homeobox genes from human, amphioxus (Branchiostoma floridae) and
      fruitfly (Drosophila melanogaster); additional species can be added. HomeoDB is
      freely accessible at (http://homeodb.cbi.pku.edu.cn).

PMID- 18803770
TI  - Conserved relative timing of cranial ossification patterns in early mammalian
      evolution.
AB  - We analyzed a comprehensive data set of ossification sequences including seven
      marsupial, 13 placental and seven sauropsid species. Data are provided for the
      first time for two major mammalian clades, Chiroptera and Soricidae, and for two
      rodent species; the published sequences of three species were improved with
      additional sampling. The relative timing of the onset of ossification in 17
      cranial elements was recorded, resulting in 136 event pairs, which were treated
      as characters for each species. Half of these characters are constant across all
      taxa, 30% are variable but phylogenetically uninformative, and 19% potentially
      deliver diagnostic features for clades of two or more taxa. Using the
      conservative estimate of heterochronic changes provided by the program Parsimov,
      only a few heterochronies were found to diagnose mammals, marsupials, or
      placentals. A later onset of ossification of the pterygoid with respect to six
      other cranial bones characterizes therian mammals. This result may relate to the
      relatively small size of this bone in this clade. One change in relative onset of
      ossification is hypothesized as a potential human autapomorphy in the context of
      the sampling made: the earlier onset of the ossification of the periotic with
      respect to the lacrimal and to three basicranial bones. Using the standard error
      of scaled ranks across all species as a measure of each element's lability in
      developmental timing, we found that ossification of early, middle, and late
      events are similarly labile, with basicranial traits the most labile in timing of
      onset of ossification. Despite marsupials and placental mammals diverging at
      least 130 Ma, few heterochronic shifts in cranial ossification diagnose these
      clades.

PMID- 18803771
TI  - Fate mapping in embryos of Neoceratodus forsteri reveals cranial neural crest
      participation in tooth development is conserved from lungfish to tetrapods.
AB  - Experimental evidence that the neural crest participates in tooth development in
      any osteichthyan fish has so far been lacking. Using vital dye cell-lineage
      tracking, we demonstrate that trigeminal stream neural crest cells contribute to
      the dental papilla of developing teeth in the Australian lungfish. Trigeminal
      neural crest cells labeled before migration have been traced during the earliest
      stages of tooth development. Neural crest cells from a single midbrain locus were
      relocated as ectomesenchyme in all developing teeth of the lungfish regardless of
      their topographical position in the dentition. These cells remain at the dental
      papilla interface and become cells committed to dentine production. Our findings
      provide the first cell-lineage evidence that cranial neural crest is fated to
      ectomesenchyme for tooth development and dentine production in the living sister
      group to tetrapods. This shows that cranial neural crest contribution to teeth is
      conserved from this node on the tetrapod phylogeny.

PMID- 18803772
TI  - Evolution of an insect-specific GROUCHO-interaction motif in the ENGRAILED
      selector protein.
AB  - Animal morphology evolves through alterations in the genetic regulatory networks
      that control development. Regulatory connections are commonly added, subtracted,
      or modified via mutations in cis-regulatory elements, but several cases are also
      known where transcription factors have gained or lost activity-modulating peptide
      motifs. In order to better assess the role of novel transcription factor peptide
      motifs in evolution, we searched for synapomorphic motifs in the homeotic
      selectors of Drosophila melanogaster and related insects. Here, we describe an
      evolutionarily novel GROUCHO (GRO)-interaction motif in the ENGRAILED (EN)
      selector protein. This "ehIFRPF" motif is not homologous to the previously
      characterized "engrailed homology 1" (eh1) GRO-interaction motif of EN. This
      second motif is an insect-specific "WRPW"-type motif that has been maintained by
      purifying selection in at least the dipteran/lepidopteran lineage. We demonstrate
      that this motif contributes to in vivo repression of the wingless (wg) target
      gene and to interaction with GRO in vitro. The acquisition and conservation of
      this auxiliary peptide motif shows how the number and activity of short peptide
      motifs can evolve in transcription factors while existing regulatory functions
      are maintained.

PMID- 18803773
TI  - Germ cell specification and early embryonic patterning in Bombyx mori as revealed
      by nanos orthologues.
AB  - In the silkmoth Bombyx mori, the germ cells first appear from the posterior
      ventral side of the egg (from within the mesodermal primordium) after blastoderm
      formation. This is in contrast to Drosophila, where germ cells appear at the
      posterior pole before cellular blastoderm formation. To date, germ plasm has not
      been found in B. mori. In this study, we describe the identification and
      expression pattern of nanos from B. mori, in which we recovered four nanos
      orthologues. One orthologue showed strong expression in embryonic germ cells,
      which was traced back to periplasmic granules dispersed on the ventral midline of
      the egg from the posterior-ventral focus of preblastoderm embryos. This suggests
      that, in B. mori, as in dipterans, germ cell formation depends on a localized
      determinant in the egg. The expression of another orthologue was observed in the
      posterior of the germ band. We speculate that nanos has dual functions; one in
      germ cell formation and the other in posterior body patterning, which is
      conferred by one nanos gene in Drosophila, but is assigned to different genes in
      B. mori.

PMID- 18803774
TI  - Class 1 KNOX genes are not involved in shoot development in the moss
      Physcomitrella patens but do function in sporophyte development.
AB  - Although the number and form of metazoan organs are determined in the embryo,
      plants continuously form organs via pluripotent stem cells contained within the
      meristem. Flowering plants have an indeterminate meristem in their diploid
      generation, whereas the common ancestor of land plants is inferred to have formed
      an indeterminate meristem in its haploid generation, as observed in the extant
      basal land plants, bryophytes, including mosses. It is hypothesized that the
      underlying gene networks for the diploid meristem were initially present in the
      haploid generation of the basal land plants and were eventually co-opted for
      expression in the diploid generation. In flowering plants, the class 1 KNOTTED1
      LIKE HOMEOBOX (KNOX) transcription factors are essential for the function of the
      indeterminate apical meristem. Here, we show that the class 1 KNOX orthologs
      function in the diploid organ, with determinate growth in the moss Physcomitrella
      patens, but do not function in the haploid indeterminate meristem. We propose
      that the genetic networks governing the indeterminate meristem in land plants are
      variable, and the networks governing the diploid indeterminate meristem with the
      class 1 KNOX genes likely evolved de novo in the flowering plant lineage.

PMID- 18803775
TI  - Global analysis of gene expression in cotton fibers from wild and domesticated
      Gossypium barbadense.
AB  - Gossypium barbadense is widely cultivated because of its extra-long staple cotton
      with superior luster, silkiness and high yield. These economically important
      traits were selected during initial domestication of an agronomically inferior
      wild ancestor, followed by millennia of human-mediated selection. To reveal the
      effects of this history on the cotton fiber transcriptome, we conducted
      comparative expression profiling on mechanically isolated fiber cells at three
      different stages encompassing early, mid, and late fiber elongation in wild
      (K101) and domesticated (Pima S-7) accessions, using a microarray platform that
      interrogates 42,429 unigenes. The distribution of differentially expressed genes
      across developmental stages was different in the two accessions, with a shift
      toward greater change earlier in cultivated than in wild G. barbadense.
      Approximately 4200 genes were differentially expressed between wild and
      domesticated accessions at one or more of the stages studied. Domestication
      appears to have led to enhanced modulation of cellular redox levels and the
      avoidance or delay of stress-like processes. Prolonged fiber growth in cultivated
      relative to wild G. barbadense is associated with upregulation of signal
      transduction and hormone signaling genes and down-regulation of cell wall
      maturation genes. Clues are provided into the processes and genes that may
      unwittingly have been selected by humans during domestication and development of
      modern elite lines. Several of the transcriptomic differences between wild and
      domesticated G. barbadense described here appear to have parallels in a second
      domesticated cotton species, Gossypium hirsutum, suggesting that replicated
      domestication of two different species has resulted in overlapping, parallel,
      metabolic transformations.

PMID- 18803776
TI  - Microevolutionary support for a developmental hourglass: gene expression patterns
      shape sequence variation and divergence in Drosophila.
AB  - A central goal of evolutionary developmental biology (Evo-Devo) is to synthesize
      comparative molecular developmental genetics and its description of the dynamic
      relationship between genotype and phenotype with the microevolutionary processes
      (mutation, random drift, and selection) of population genetics. To this end, we
      analyzed sequence variation of five gene classes that act sequentially to shape
      early embryo development in Drosophila: maternal, gap, pair-rule, segment
      polarity, and segment identity genes. We found two related patterns: (1) a
      microevolutionary pattern, wherein relative sequence variation within species is
      2- to 3-fold higher for maternal-effect genes than for any other gene class; and,
      (2) a macroevolutionary pattern, wherein the relative sequence divergence among
      species for maternal-effect genes is 2- to 4-fold greater than for any other gene
      class. Both patterns are qualitatively and quantitatively consistent with the
      predictions of microevolutionary theory. Our findings connect within-species
      genetic variation to between-species divergence and shed light on the controversy
      over the existence of a "developmental hourglass," where mid-embryonic stages are
      more evolutionarily constrained than either earlier or later stages. Because
      maternal-effect genes experience relaxed selective constraint relative to zygotic
      effect genes, they explore a wider mutational and phenotypic space. As a result,
      early acting maternal-effect genes diverge more widely across taxa and thereby
      broaden the base of the developmental hourglass. In contrast, later acting
      zygotic genes are relatively more constrained and limited in their
      diversification across taxa, narrowing the waist of the developmental hourglass.
      This pattern is obscured by genes with both maternal and zygotic expression,
      which experience the strongest evolutionary constraint.

PMID- 18803777
TI  - Vascular regeneration and angiogenic-like sprouting mechanism in a compound
      ascidian is similar to vertebrates.
AB  - Tunicates are useful models for comparing differing developmental processes such
      as embryogenesis, asexual reproduction, and regeneration, because they are the
      closest relatives to vertebrates and are the only chordates to reproduce both
      sexually and asexually. Among them, the ascidian Botryllus schlosseri displays
      high regenerative potential of the colonial circulatory system (CCS). The CCS
      runs in the common tunic, forming an anastomized network of vessels defined by
      simple epithelia and connected to the open circulatory system of the zooids.
      During asexual propagation, new vessels form by means of a tubular-sprouting
      mechanism, resembling that occurring in other metazoans, particularly during
      vertebrate angiogenesis. We studied the regeneration of experimentally ablated
      CCS by analyzing the general dynamics of reorganization of vessels and tunic,
      their ultrastructure, cell proliferation, and the immunohistology of regenerating
      structures using antibodies against vertebrate angiogenic factors-vascular
      endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2), epidermal
      growth factor (EGF), and receptors: VEGFR-1, VEGFR-2, and EGFR. Results show that
      the regenerative process of CCS occurs by a sprouting mechanism, with
      participation of angiogenic factors. They also show correspondence between the
      CCS sprouting of B. schlosseri and angiogenic sprouting in vertebrates, during
      both normal development and regeneration, and support the idea that this
      morphogenetic mechanism was co-opted during the evolution of various
      developmental processes in different taxa.

PMID- 18803778
TI  - Larval neurogenesis in Sabellaria alveolata reveals plasticity in polychaete
      neural patterning.
AB  - The investigation of neurogenesis in polychaetes not only facilitates insights
      into the developmental biology of this group, but also provides new data for
      phylogenetic analyses. This should eventually lead toward a better understanding
      of metazoan evolution including key issues such as the ontogenetic processes that
      underlie body segmentation. We here document the development of the larval
      nervous system in the polychaete Sabellaria alveolata using fluorescence-coupled
      antibodies directed against serotonin, FMRFamide, and tubulin in combination with
      confocal laser scanning microscopy and 3D reconstruction software. The overall
      pattern of neurogenesis in S. alveolata resembles the condition found in other
      planktonic polychaete trochophores where the larval neural body plan including a
      serotonergic prototroch nerve ring is directly followed by adult features of the
      nervous system such as circumesophageal connectives and paired ventral nerve
      cords. However, distinct features are also found in S. alveolata, such as the
      innervation of the apical organ with ring-shaped neurons, the low number of
      immunoreactive perikarya, and the lack of a posterior serotonergic cell.
      Moreover, in the larvae of S. alveolata, two distinct modes of neuronal
      development are expressed, viz. the simultaneous formation of the first three
      segmental neurons of the peripheral nervous system on the one hand versus the
      sequential appearance of the ventral commissures on the other. This highlights
      the complex mechanisms that underlie annelid body segmentation and indicates
      divergent developmental pathways within polychaete annelids that lead to the
      segmented nervous system of the adult.

PMID- 18803779
TI  - Radical modification of the A-P axis and the evolution of asexual reproduction in
      Convolutriloba acoels.
AB  - Acoel worms in the genus Convolutriloba are remarkable in that closely related,
      morphologically very similar species reproduce asexually by dramatically
      different processes. Transverse fission, longitudinal fission, and reversed
      polarity budding all occur within this genus, indicating an unparalleled ability
      to alter the A-P axis. Convolutriloba thus offers an exceptional opportunity to
      investigate the development and evolution of asexual reproduction. Molecular
      phylogenetic analysis indicates that reversed-polarity budding is ancestral and
      fission is derived for the genus. A clear difference between budding and fission
      is indicated by the development of the nervous system, which forms de novo during
      budding, but regenerates largely by extensions of remaining components of the
      nervous system during both types of fission. Despite this and other differences
      between fission and budding, localized muscle disorganization coupled with
      behaviorally mediated tearing are characteristic of both transverse fission and
      reversed-polarity budding (though not longitudinal fission), suggesting that a
      homologous tissue-separation mechanism underlies these two outwardly quite
      different asexual reproductive modes. We suggest that the ability to split the
      posterior axis field into two adjacent fields, manifested during both reversed
      polarity budding and longitudinal fission, may have been a driving force behind
      the diversification of asexual reproductive mode in this group.

PMID- 18803780
TI  - Evolutionary history of larval skeletal morphology in sea urchin Echinometridae
      (Echinoidea: Echinodermata) as deduced from mitochondrial DNA molecular
      phylogeny.
AB  - The larval skeletons of sea urchins show considerable morphological diversity,
      even between closely related species, although the evolutionary history and
      functional significance of this diversity are poorly understood. To infer the
      evolutionary history of the skeletal morphology, we focused on echinometrid
      species for which the morphological variation in larval skeletons had been
      investigated qualitatively and quantitatively. We reconstructed the phylogenetic
      relationships among 14 echinometrid species based on mitochondrial ND1 and ND2
      genes and mapped the morphological characters onto the resultant trees. The
      monophyly of each genus in the Echinometridae was well supported by our results,
      as was the close affinity between Colobocentrotus, Heterocentrotus, and
      Echinometra. The mapping of the morphological characters of the larval skeletons
      indicated that the length, direction, and density of spines on the postoral rods
      was well conserved in each group of Echinometridae and that the abundance of
      spines and the size and shape of the body skeleton changed relatively frequently
      and hence were less conserved. In Echinometrid species, morphological variation
      in relatively unconserved features tends to be associated with latitudinal
      distributions, rather than phylogenetic relationships, indicating that the
      morphological diversity of larval skeletons could have been caused by adaptation
      to the habitat environment. Some morphological differences, however, seem to be
      nonfunctional and generated by the constraints on larval skeletogenesis. Thus,
      echinometrid species can be a good model with which to study the evolutionary
      history from both ecological and developmental standpoints.

PMID- 18803782
TI  - Erratum.

PMID- 18803781
TI  - Evolutionary origins of novel conchologic growth patterns in tropical American
      corbulid bivalves.
AB  - We conducted a combined sclerochronologic and phylogenetic analysis to document
      patterns and rates of shell accretion in several subclades of related corbulids,
      and to explore the evolutionary origins of novel conchologic developmental
      patterns. We found three disparate patterns of valve development in Neogene
      tropical American corbulid genera. These patterns include growth through
      primarily radial accretion along the sagittal plane, and two derivative patterns:
      one characterized by initial deposition of a thin shell followed by valve
      thickening with little increase in valve height, and another producing a well
      defined nepioconch through a marked change in the primary growth direction. We
      conducted a species-level phylogenetic analysis of the taxa surveyed for growth
      patterns, focusing on the ([Bothrocorbula+Hexacorbula]+Caryocorbula) clade. The
      phylogenetic distribution of shell growth patterns suggests that this clade is
      characterized by derivative patterns of growth. Oxygen-isotope calibrated
      ontogenetic age estimates of species in the derived Bothrocorbula subclade
      further suggest that transitions from the ancestral radial (sagittal) growth
      pattern to a derived pattern of growth are a function of heterochrony
      (peramorphosis by acceleration). These findings are significant because they link
      previously observed patterns of morphological constraint with a specific
      evolutionary process, demonstrate how morphologic constraint and innovation can
      be interrelated, and serve as a model for understanding the evolution of
      morphologic diversity in the clade as a whole. Furthermore, this study highlights
      the utility of sclerochronologic records as an important component of
      evolutionary developmental research on organisms with accretionary skeletal
      growth.

PMID- 18803783
TI  - More or less genetic variation - with exact management.

PMID- 18803784
TI  - Optimized management of genetic variability in selected pig populations.
AB  - Controlling the increase of coancestry and inbreeding coefficients in selected
      populations is made possible through calculation of the optimal contributions
      allowed to breeding animals, given the current situation with regard to genetic
      diversity, and further, through optimal design of matings. The potential of such
      an approach for pig breeding was tested by retrospective optimization on the
      French Landrace population in reference to the matings actually carried out
      during a 21-week test period. The major constraint was that the average overall
      estimated breeding value (EBV) should be the same as the observed one, for not
      decreasing short-term genetic gain. Optimizing breeding allocations to boars
      would have led one to decrease coancestry and inbreeding coefficients by
      approximately 20%. This decrease would have even increased to approximately 30%,
      would have replacements and disposals been optimized after accounting for genetic
      variability, keeping the same constraint of genetic level identical to the
      observed one. These results showed the potential value, in the future, of
      completing each periodical calculation of EBVs by optimizations considering
      genetic variability and of releasing corresponding information to breeders, in
      order to enhance maintenance of genetic variability.

PMID- 18803785
TI  - Application of individual increase in inbreeding to estimate realized effective
      sizes from real pedigrees.
AB  - The objective of this study was to test the performance of a recently proposed
      methodology for the estimation of realized effective size (N(e)) based on
      individual increase in inbreeding (DeltaF(i)) on several real pedigrees: (a) an
      experimental mice population; (b) a closed pedigree of fighting bulls; (c) the
      Spanish Purebred (SPB, Andalusian) horse pedigree; (d) the Carthusian strain of
      SPB pedigree; (e) the Spanish Arab horse pedigree; and (f) the Spanish Anglo-Arab
      horse pedigree. Several reference subpopulations were defined on the basis of
      generation length in order to consider only animals in the last generation, to
      assess the influence of the pedigree content on the estimates of N(e). The
      estimates of realized N(e) computed from DeltaF(i) (Ne) tended to be higher than
      those obtained from regression on equivalent generations. The new parameter Ne
      remained approximately stable when pedigree depth achieved about five equivalent
      generations. Estimates of take into account the genetic history of the
      populations, the size of their founder population, and the mating policy or
      bottlenecks caused by poor use of reproducing individuals. The usefulness of the
      realized N(e) computed from individual increase in inbreeding in real pedigrees
      is also discussed.

PMID- 18803786
TI  - Design of a village breeding programme for a llama population in the High Andes
      of Bolivia.
AB  - No national breeding programme for llamas is in place in Bolivia. Initiatives for
      genetic improvement are rarely found and are usually carried out by NGOs working
      in rural development or improvement of livestock production or research stations.
      Farmers in the Province of Ayopaya in the District of Cochabamba have formed a
      breeders' organization with the aim of improving fibre production. In this study,
      a detailed outline of a breeding programme with a focus on organizational and
      technical details is described. Facing constraints like illiteracy of farmers,
      bad infrastructure and lack of finances, a simple breeding programme is set up.
      The breeding goal is a higher fleece weight while keeping the fleece quality at
      the current high level. Greasy fleece weight and fibre diameter are identified as
      main selection criteria. Mass selection of males is carried out. Selected males
      are either exchanged between farmers and used in the herds or are kept during the
      mating season in a central mating station owned by the breeders' organization.
      Model calculations were carried out with the program zplan, which is based on a
      deterministic approach. zplan evaluates the genetic and economic efficiency of
      breeding strategies considering one cycle of selection. Scenarios with only intra
      herd use, using only the central mating station or combinations of those were
      compared in terms of expected genetic gain and expected increase of inbreeding.
      Fastest genetic progress is achieved when the males are kept in a central mating
      station as the selection intensity is on a high level. Rates of inbreeding vary
      between 0.08 and 0.32% per generation.

PMID- 18803787
TI  - Selection on multiple QTL with control of gene diversity and inbreeding for long
      term benefit.
AB  - The purpose of this study was to develop and investigate selection strategies
      that aim at maximizing long-term genetic response while conserving gene diversity
      and controlling inbreeding in populations of limited effective size, assuming
      complete knowledge of all genes affecting a quantitative trait. Three selection
      strategies were proposed to select on 100 quantitative trait loci (QTL) and
      compared with truncation selection on breeding value. Alternative selection
      strategies aimed at maximizing the average breeding value of parents with a
      penalty on (1) the number of unfavourable QTL genotypes among parents (OS-I), (2)
      the negative of the logarithm of the frequency of the favourable allele at each
      QTL among parents (OS-II), and (3) the average pedigree relationship among
      parents (OS-III). When all QTL and their effects were known, the strategies
      examined were able to obtain extra long-term responses, conserve QTL diversity
      and reduce inbreeding, compared with truncation selection. Strategy OS-II was the
      most effective in conserving QTL diversity and OS-III in reducing inbreeding. By
      changing the magnitude of the penalties applied, the impact on long-term
      response, inbreeding and diversity can be controlled. Extra long-term responses
      over truncation selection of OS-I and OS-II were even greater when effects of QTL
      were estimated rather than assumed known, indicating the applicability of results
      to practical strategies for marker-assisted selection. Extra responses are
      expected to be reduced for larger population sizes.

PMID- 18803788
TI  - Sampling genotype configurations in a large complex pedigree.
AB  - Many genetic problems can be solved by Monte Carlo method. This often requires
      sampling genotype configurations over pedigree. Current available samplers are
      inefficient for large animal pedigrees. A new sampler suitable for large complex
      pedigrees has been developed and evaluated. The sampler uses simple and iterative
      peeling algorithms alternately. The sampler was compared to two other samplers on
      hypothetical pedigree of 79 individuals and recessive disease. The behaviour of
      the sampler was evaluated in four experimental designs on real bovine pedigree of
      907,903 animals. The application of the sampler was also exemplified in identical
      by descent study.

PMID- 18803789
TI  - PMCHAP: a new approach for haplotype inference using nuclear families with only
      one parent and multiple offspring.
AB  - A new approach is suggested to perform joint haplotype reconstruction and
      haplotype frequency estimation in families consisting of multiple full sibs where
      only one parent is genotyped. It can also deal with the mixed data structures
      with 0 and 1 parent genotyped. The approach is based on the maximum likelihood
      principle using the expectation-maximization algorithm and thus combines pedigree
      information within families and linkage disequilibrium information between
      families with assumption of no recombination. In a simulation study of single
      nucleotide polymorphisms, the new algorithm termed PMCHAP (parent multiple
      children haplotyping) is shown to provide significantly better results than an
      approximation used so far, especially providing better estimates with increasing
      family sizes. It will be especially helpful for research in multiparous species
      like pigs, dogs, fish, and many lab animals where it is easy to collect families
      with multiple siblings.

PMID- 18803790
TI  - Optimal utilization of non-additive quantitative trait locus in animal breeding
      programs.
AB  - Optimal selection on a single identified quantitative trait locus (QTL) with four
      modes of inheritance: normal autosomal, sex-limited, imprinting and X-linked, was
      evaluated in four breeding structures: single line selection (SLS), two-way
      crossing (2WC), three-way crossing (3WC) and reciprocal crossing (RC) by
      comparing extra benefit from mate selection over index selection to demonstrate
      effectiveness of mate selection in exploiting non-additive QTL. The results
      showed that the superiority varied at different QTL inheritance modes, initial
      favourable allele frequencies and breeding structures. The superiority tended to
      decrease with the increase of the favourable allele frequency except for over
      dominant QTL and imprinted QTL in all breeding structures. Less superiority
      (below 9%) was observed for a recessive and a fully dominant QTL than for an over
      dominant QTL (up to 27.11%). Normal autosomal and sex-linked QTL led to a similar
      trend of superiority from mate selection but the magnitude of the superiority
      with the latter was slightly higher than with the former for most combinations of
      the parameters. A high superiority (6.41-41.54%) was observed from mate selection
      over index selection for an imprinted QTL. A maternally imprinted QTL tended to
      lead to higher superiority from mate selection than a paternally imprinted QTL. X
      linked QTL led to less superiority from mate selection than the other modes of
      QTL. A larger superiority from mate selection was observed for a recessive and a
      fully dominant QTL in structures 3WC and 2WC than structures RC and SLS. The
      superiority from autosomal QTL and X-linked QTL was lower in the structure RC
      than in other structures examined.

PMID- 18803791
TI  - Genetic analysis of Mexican Criollo cattle populations.
AB  - The objective of this study was to evaluate the genetic structure of Mexican
      Criollo cattle populations using microsatellite genetic markers. DNA samples were
      collected from 168 animals from four Mexican Criollo cattle populations,
      geographically isolated in remote areas of Sierra Madre Occidental (West
      Highlands). Also were included samples from two breeds with Iberian origin: the
      fighting bull (n = 24) and the milking central American Criollo (n = 24) and one
      Asiatic breed: Guzerat (n = 32). Genetic analysis consisted of the estimation of
      the genetic diversity in each population by the allele number and the average
      expected heterozygosity found in nine microsatellite loci. Furthermore, genetic
      relationships among the populations were defined by their genetic distances. Our
      data shows that Mexican cattle populations have a relatively high level of
      genetic diversity based either on the mean number of alleles (10.2-13.6) and on
      the expected heterozygosity (0.71-0.85). The degree of observed homozygosity
      within the Criollo populations was remarkable and probably caused by inbreeding
      (reduced effective population size) possibly due to reproductive structure within
      populations. Our data shows that considerable genetic differentiation has been
      occurred among the Criollo cattle populations in different regions of Mexico.

PMID- 18803792
TI  - Perspectives on Sexual and Reproductive Health. In this issue.

PMID- 18803794
TI  - Pleasure, prophylaxis and procreation: a qualitative analysis of intermittent
      contraceptive use and unintended pregnancy.
AB  - CONTEXT: Although pregnancy ambivalence is consistently associated with poorer
      contraceptive use, little is known about the sexual, social and emotional
      dynamics at work in pregnancy ambivalence. METHODS: During in-depth sexual and
      reproductive history interviews conducted in 2003, 36 women and men were asked
      about the relational and emotional circumstances surrounding each pregnancy, as
      well as their thoughts about conceiving a baby with both current and previous
      partners. An ethnographic, inductive approach was used to analyze the data.
      RESULTS: Half of respondents had experienced at least one unintended pregnancy.
      Respondents described three categories of pleasure related to pregnancy
      ambivalence: active eroticization of risk, in which pregnancy fantasies
      heightened the charge of the sexual encounter; passive romanticization of
      pregnancy, in which people neither actively sought nor prevented conception; and
      an escapist pleasure in imagining that a pregnancy would sweep one away from
      hardship. All three categories were associated with misuse or nonuse of coitus
      dependent methods. CONCLUSIONS: For some individuals, the perceived emotional and
      sexual benefits of conception may outweigh the goal of averting conception, even
      when a child is not wholly intended. Future behavioral studies should collect
      more nuanced data on pregnancy-related pleasure. Clinicians and patients would
      benefit from clearer guidelines for assessing ambivalence and for linking
      ambivalent clients with longer-acting methods that are not coitus-dependent.

PMID- 18803795
TI  - Prior pill experiences and current continuation among pill restarters.
AB  - CONTEXT: Discontinuation of oral contraceptives often puts women at risk for
      unintended pregnancies. Understanding why a woman discontinued pill use can
      provide insight into her risk of discontinuation if she restarts use. METHODS:
      Women younger than 25 obtaining oral contraceptives at three university health
      centers in 2003-2005 were recruited to participate in a randomized trial; 628
      former users were interviewed about their previous experience with the method,
      and were followed up three months after restarting use. Bivariate and multinomial
      logistic regression analyses were used to assess the relationship between prior
      reasons for stopping pill use and method continuation. RESULTS: Women who had
      discontinued using oral contraceptives because of side effects were less likely
      to be very sure about restarting the pill at baseline (73%) than were those who
      had stopped for logistical or fertility-related reasons (88-94%). They also were
      less likely to have been satisfied with the pill in the last use interval (49%
      vs. 95-98%) and less likely to be satisfied with it in the three months after
      restarting (76% vs. 89-93%). These women were more likely to report a short
      duration of use than an intermediate duration or continuous use during follow-up
      (odds ratios, 2.5 and 4.5). CONCLUSIONS: When counseling women who are restarting
      pill use, providers should ask about their experiences with the method and
      reasons for discontinuation; counseling for women who discontinued because of
      side effects should address their risk factors for early discontinuation and
      informing them about other contraceptive choices.

PMID- 18803796
TI  - Recent evaluations of the peer-led approach in adolescent sexual health
      education: a systematic review.
AB  - CONTEXT: Peer-led interventions have become a popular method of providing sexual
      health education to adolescents, but the efficacy of this approach and the
      methodological quality of recent trials have not been systematically reviewed.
      METHODS: Electronic and hand searches were conducted to identify quasi-randomized
      and randomized controlled trials of peer-led adolescent sexual health education
      published from 1998 to 2005. Studies were eligible if they had an appropriate
      comparison group, provided preintervention and postintervention data, and
      reported all outcomes. Study results were summarized and, where appropriate,
      pooled; in addition, 10 aspects of studies' methodological quality were assessed.
      RESULTS: Thirteen articles met the inclusion criteria. Pooled, adjusted results
      from seven trials that examined the effects of peer-led interventions on condom
      use at last sex found no overall benefit (odds ratio, 1.0). None of the three
      trials that assessed consistent condom use found a benefit. One study reported a
      reduced risk of chlamydia (0.2), but another found no impact on STD incidence.
      One study found that young women (but not young men) who received peer-led
      education were more likely than nonrecipients to have never had sex. Most
      interventions produced improvements in knowledge, attitudes and intentions. Only
      three studies fulfilled all 10 of the assessed quality criteria; two others met
      nine criteria. CONCLUSIONS: Despite promising results in some trials, overall
      findings do not provide convincing evidence that peer-led education improves
      sexual outcomes among adolescents. Future trials should build on the successful
      trials conducted to date and should strive to fulfill existing quality criteria.

PMID- 18803797
TI  - Timing of sexual debut and initiation of postsecondary education by early
      adulthood.
AB  - CONTEXT: Although sexual debut has been negatively associated with adolescent
      educational performance and aspirations, it is not clear whether such
      relationships continue beyond adolescence. METHODS: Initiation of postsecondary
      education by young adulthood was assessed among 3,965 participants in the
      National Longitudinal Study of Adolescent Health who had not experienced sexual
      intercourse at baseline. Associations between age at sexual debut and educational
      progress were examined in bivariate and multivariable Poisson regression
      analyses. RESULTS: Most respondents experienced sexual debut during adolescence:
      15% before age 16 (early) and 53% at ages 16-18 (typical). Sixty-five percent of
      respondents initiated postsecondary education by early adulthood; however, the
      proportion was significantly lower among those who had had an early (49%) or
      typical sexual debut (63%) than among those who debuted late (78%). In unadjusted
      analyses, early and typical debut were associated with a reduced likelihood of
      initiation of postsecondary education for both females (relative risk ratios, 0.6
      and 0.8, respectively) and males (0.7 and 0.8). However, in adjusted analyses,
      the associations were attenuated for females (0.8 and 0.9) and were at best
      marginally significant for males. Childbearing was a significant mediator of this
      relationship. CONCLUSIONS: Adolescent sexual debut appears to be modestly
      negatively associated with early adult postsecondary education initiation,
      particularly for females. Targeting mediators of the sexual debut-education
      relationship, such as early childbearing, could lead to effective interventions.

PMID- 18803798
TI  - Implementing an advance emergency contraception policy: what happens in the real
      world?
AB  - CONTEXT: Advance provision of emergency contraception increases the likelihood of
      its use, yet little is known about the factors that influence successful
      implementation of an advance provision policy in publicly funded family planning
      clinics. METHODS: Data on knowledge of, attitudes toward and use of emergency
      contraception were collected from 211 patients attending four Title X-funded
      clinics in Pennsylvania in 2001-2002. In addition, 22 staff from the four clinics
      were interviewed regarding barriers to and facilitators of advance provision in
      2004-2005, and 111 staff from 46 clinics completed related surveys in 2005.
      Qualitative data underwent content analysis, and frequencies and bivariate
      associations between variables were calculated for the survey data. RESULTS: Most
      patients said they would use emergency contraception (80%) and believed it should
      be easy to obtain (93%), although 46% thought it is a form of abortion. Patients'
      familiarity with the method, attitudes toward it and self-efficacy regarding its
      use were not associated with most demographic or reproductive health
      characteristics. While nearly all interviewed staff endorsed routine advance
      provision, only about half of survey respondents offered it "very often" at
      patients' initial or annual visits. Barriers to advance provision included staff
      prejudgment of patients' needs and ability to use the method, time constraints
      and inefficiencies in clinic procedures. CONCLUSIONS: Strategies that may
      facilitate advance provision of emergency contraception include emphasizing the
      need for staff to offer it during all patient visits, providing patient-friendly
      information and streamlining clinic procedures.

PMID- 18803799
TI  - Associations between low-income women's relationship characteristics and their
      contraceptive use.
AB  - CONTEXT: Women's relationship context likely influences both their ability and
      their motivation to use contraceptives. No recent studies, however, have examined
      associations between women's relationship characteristics and use of different
      methods. METHODS: Data were collected in a longitudinal study of 839 low-income
      women at risk of unintended pregnancy who visited public family planning and
      postpartum clinics and maternity wards in two Southeastern cities. Simulated
      probabilities calculated from multivariate analyses assessed associations between
      a wide range of relationship characteristics and the use of no method, condoms,
      withdrawal, female methods or dual methods. RESULTS: Women who had had a child
      with their partner had an increased likelihood of contraceptive nonuse and use of
      withdrawal, and a decreased likelihood of using any female method. Respondents
      who were in a relationship for a relatively long time had an elevated likelihood
      of nonuse and use of female methods, but a lowered likelihood of condom use.
      Furthermore, married or cohabiting women were less likely than others to use dual
      methods. Respondents who had good communication with their partner had an
      elevated likelihood of using condoms. In addition, women who expected to receive
      a lot of emotional support from their partner if they became pregnant were more
      likely than others to report any condom use or dual method use, and less likely
      to report contraceptive nonuse. CONCLUSIONS: When counseling family planning
      clients, providers should consider women in the context of their relationships.
      Future research exploring factors associated with contraceptive method use should
      examine variables related to the establishment, quality and expectations of their
      relationships.

PMID- 18803808
TI  - Alpha-CaMKII deficiency causes immature dentate gyrus, a novel candidate
      endophenotype of psychiatric disorders.
AB  - Elucidating the neural and genetic factors underlying psychiatric illness is
      hampered by current methods of clinical diagnosis. The identification and
      investigation of clinical endophenotypes may be one solution, but represents a
      considerable challenge in human subjects. Here we report that mice heterozygous
      for a null mutation of the alpha-isoform of calcium/calmodulin-dependent protein
      kinase II (alpha-CaMKII+/-) have profoundly dysregulated behaviours and impaired
      neuronal development in the dentate gyrus (DG). The behavioral abnormalities
      include a severe working memory deficit and an exaggerated infradian rhythm,
      which are similar to symptoms seen in schizophrenia, bipolar mood disorder and
      other psychiatric disorders. Transcriptome analysis of the hippocampus of these
      mutants revealed that the expression levels of more than 2000 genes were
      significantly changed. Strikingly, among the 20 most downregulated genes, 5 had
      highly selective expression in the DG. Whereas BrdU incorporated cells in the
      mutant mouse DG was increased by more than 50 percent, the number of mature
      neurons in the DG was dramatically decreased. Morphological and physiological
      features of the DG neurons in the mutants were strikingly similar to those of
      immature DG neurons in normal rodents. Moreover, c-Fos expression in the DG after
      electric footshock was almost completely and selectively abolished in the
      mutants. Statistical clustering of human post-mortem brains using 10 genes
      differentially-expressed in the mutant mice were used to classify individuals
      into two clusters, one of which contained 16 of 18 schizophrenic patients. Nearly
      half of the differentially-expressed probes in the schizophrenia-enriched cluster
      encoded genes that are involved in neurogenesis or in neuronal
      migration/maturation, including calbindin, a marker for mature DG neurons. Based
      on these results, we propose that an "immature DG" in adulthood might induce
      alterations in behavior and serve as a promising candidate endophenotype of
      schizophrenia and other human psychiatric disorders.

PMID- 18803809
TI  - Comprehensive behavioral phenotyping of calpastatin-knockout mice.
AB  - BACKGROUND: Calpastatin is an endogenous inhibitor of calpain, intracellular
      calcium-activated protease. It has been suggested to be involved in molecular
      mechanisms of long-term plasticity and excitotoxic pathways. However, functions
      of calpastatin in vivo are still largely unknown. To examine the physiological
      roles of calpastatin, we subjected calpastatin-knockout mice to a comprehensive
      behavioral test battery. RESULTS: Calpastatin-knockout mice showed decreased
      locomotor activity under stressful environments, and decreased acoustic startle
      response, but we observed no significant change in hippocampus-dependent memory
      function. CONCLUSION: These results suggest that calpastatin is likely to be more
      closely associated with affective rather than cognitive aspects of brain
      function.

PMID- 18803810
TI  - Can colorectal cancer mass-screening organization be evidence-based? Lessons from
      failures: the experimental and pilot phases of the Lazio program.
AB  - BACKGROUND: Screening programmes should be organized to translate theoretical
      efficacy into effectiveness. An evidence-based organizational model of colorectal
      cancer screening (CRCS) should assure feasibility and high compliance. METHODS: A
      multidisciplinary Working Group (WG), reviewed literature and guidelines to
      define evidence-based recommendations. The WG identified the need for further
      local studies: physicians' CRCS attitudes, the effect of test type and provider
      on compliance, and individual reasons for non-compliance. A survey of digestive
      endoscopy services was conducted. A feasibility study on a target population of
      300.000 has begun. RESULTS: Based on the results of population trials and on
      literature review the screening strategy adopted was Faecal Occult Blood Test
      (FOBT) every two years for 50-74 year olds and, for positives, colonoscopy. The
      immunochemical test was chosen because it has 20% higher compliance than the
      Guaiac. GPs were chosen as the preferred provider also for higher compliance.
      Since we observed that distance is the major determinant of non-compliance, we
      choose GPs because they are the closest providers, both geographically and
      emotionally, to the public. The feasibility study showed several barriers: GP
      participation was low, there were administrative problems to involve GPs;
      opportunistic testing by the GPs; difficulties in access to Gastroenterology
      centres; difficulties in gathering colonoscopy results; little time given to
      screening activity by the gastroenterology centre. CONCLUSION: The feasibility
      study highlighted several limits of the model. Most of the barriers that emerged
      were consequences of organisational choices not supported by evidence. The
      principal limit was a lack of accountability by the participating centres.

PMID- 18803811
TI  - Prevalence of variations in melanoma susceptibility genes among Slovenian
      melanoma families.
AB  - BACKGROUND: Two high-risk genes have been implicated in the development of CM
      (cutaneous melanoma). Germline mutations of the CDKN2A gene are found in < 25% of
      melanoma-prone families and there are only seven families with mutation of the
      CDK4 gene reported to date. Beside those high penetrance genes, certain allelic
      variants of the MC1R gene modify the risk of developing the disease. THE AIMS OF
      OUR STUDY WERE: to determine the prevalence of germline CDKN2A mutations and
      variants in members of families with familial CM and in patients with multiple
      primary CM; to search for possible CDK4 mutations, and to determine the frequency
      of variations in the MC1R gene. METHODS: From January 2001 until January 2007, 64
      individuals were included in the study. The group included 28 patients and 7
      healthy relatives belonging to 25 families, 26 patients with multiple primary
      tumors and 3 children with CM. Additionally 54 healthy individuals were included
      as a control group. Mutations and variants of the melanoma susceptibility genes
      were identified by direct sequencing. RESULTS: Seven families with CDKN2A
      mutations were discovered (7/25 or 28.0%). The L94Q mutation found in one family
      had not been previously reported in other populations. The D84N variant, with
      possible biological impact, was discovered in the case of patient without family
      history but with multiple primary CM. Only one mutation carrier was found in the
      control group. Further analysis revealed that c.540C>T heterozygous carriers were
      more common in the group of CM patients and their healthy relatives (11/64 vs.
      2/54). One p14ARF variant was discovered in the control group and no mutations of
      the CDK4 gene were found. Most frequently found variants of the MC1R gene were
      T314T, V60L, V92M, R151C, R160W and R163Q with frequencies slightly higher in the
      group of patients and their relatives than in the group of controls, but the
      difference was statistically insignificant. CONCLUSION: The present study has
      shown high prevalence of p16INK4A mutations in Slovenian population of familial
      melanoma patients (37%) and an absence of p14ARF or CDK4 mutations.

PMID- 18803812
TI  - What advice are oncologists and surgeons in the United Kingdom giving to breast
      cancer patients about physical activity?
AB  - Evidence has shown that physical activity may attenuate the negative physical,
      psychological and functional effects of treatment in women diagnosed with breast
      cancer. Physical activity levels also decline substantially during and after
      completion of treatment for cancer, highlighting the importance of strategies to
      promote participation in regular physical activity in this population.
      Oncologists and surgeons may serve as an influential source of motivation to be
      physically activity in cancer patients, by conveying the importance of a healthy
      lifestyle. The primary purpose of the present study was to investigate whether
      oncologists and surgeons routinely discuss physical activity with their breast
      cancer patients and to investigate the nature of any information/advice provided
      during consultations. A secondary aim was to examine whether physically active
      oncologists and surgeons were more likely to provide advice about physical
      activity to patients, than inactive oncologists and surgeons. A brief postal
      questionnaire was sent to 710 consultant breast cancer oncologists and surgeons
      throughout the UK and 102 responded (response rate = 14.4%). Of responders, most
      (55.9%) did not routinely discuss physical activity with their patients. Amongst
      oncologists/surgeons (clinicians) who did offer advice, most focussed on
      discussing the benefits of physical activity for physical and functional health
      gains and for facilitating weight control and maintenance. A number of clinicians
      indicated they advised patients that physical activity may decrease risk of
      recurrence and improve survival, despite the lack of evidence from RCTs to
      support this suggestion. There was no significant association between the
      physical activity status of oncologists/surgeons and the likelihood that they
      discussed physical activity with patients. Educational strategies aimed at
      encouraging clinicians to promote physical activity in consultations need to be
      targeted widely amongst the cancer clinician community.

PMID- 18803813
TI  - A large population of diverse neurons in the Drosophila central nervous system
      expresses short neuropeptide F, suggesting multiple distributed peptide
      functions.
AB  - BACKGROUND: Insect neuropeptides are distributed in stereotypic sets of neurons
      that commonly constitute a small fraction of the total number of neurons.
      However, some neuropeptide genes are expressed in larger numbers of neurons of
      diverse types suggesting that they are involved in a greater diversity of
      functions. One of these widely expressed genes, snpf, encodes the precursor of
      short neuropeptide F (sNPF). To unravel possible functional diversity we have
      mapped the distribution of transcript of the snpf gene and its peptide products
      in the central nervous system (CNS) of Drosophila in relation to other neuronal
      markers. RESULTS: There are several hundreds of neurons in the larval CNS and
      several thousands in the adult Drosophila brain expressing snpf transcript and
      sNPF peptide. Most of these neurons are intrinsic interneurons of the mushroom
      bodies. Additionally, sNPF is expressed in numerous small interneurons of the
      CNS, olfactory receptor neurons (ORNs) of the antennae, and in a small set of
      possibly neurosecretory cells innervating the corpora cardiaca and aorta. A sNPF
      Gal4 line confirms most of the expression pattern. None of the sNPF
      immunoreactive neurons co-express a marker for the transcription factor DIMMED,
      suggesting that the majority are not neurosecretory cells or large interneurons
      involved in episodic bulk transmission. Instead a portion of the sNPF producing
      neurons co-express markers for classical neurotransmitters such as acetylcholine,
      GABA and glutamate, suggesting that sNPF is a co-transmitter or local
      neuromodulator in ORNs and many interneurons. Interestingly, sNPF is coexpressed
      both with presumed excitatory and inhibitory neurotransmitters. A few sNPF
      expressing neurons in the brain colocalize the peptide corazonin and a pair of
      dorsal neurons in the first abdominal neuromere coexpresses sNPF and insulin-like
      peptide 7 (ILP7). CONCLUSION: It is likely that sNPF has multiple functions as
      neurohormone as well as local neuromodulator/co-transmitter in various CNS
      circuits, including olfactory circuits both at the level of the first synapse and
      at the mushroom body output level. Some of the sNPF immunoreactive axons
      terminate in close proximity to neurosecretory cells producing ILPs and
      adipokinetic hormone, indicating that sNPF also might regulate hormone production
      or release.

PMID- 18803814
TI  - Serum S100B levels after meningioma surgery: A comparison of two laboratory
      assays.
AB  - BACKGROUND: S100B protein is a potential biomarker of central nervous system
      insult. This study quantitatively compared two methods for assessing serum
      concentration of S100B. METHODS: A prospective, observational study performed in
      a single tertiary medical center. Included were fifty two consecutive adult
      patients undergoing surgery for meningioma that provided blood samples for
      determination of S100B concentrations. Eighty samples (40 pre-operative and 40
      postoperative) were randomly selected for batch testing. Each sample was divided
      into two aliquots. These were analyzed by ELISA (Sangtec) and a commercial kit
      (Roche Elecsys(R)) for S100B concentrations. Statistical analysis included
      regression modelling and Bland-Altman analysis. RESULTS: A parsimonious linear
      model best described the prediction of commercial kit values by those determined
      by ELISA (y = 0.045 + 0.277*x, x = ELISA value, R2 = 0.732). ELISA measurements
      tended to be higher than commercial kit measurements. This discrepancy increased
      linearly with increasing S100B concentrations. At concentrations above 0.7
      microg/L the paired measurements were consistently outside the limits of
      agreement in the Bland-Altman display. Similar to other studies that used
      alternative measurement methods, sex and age related differences in serum S100B
      levels were not detected using the Elecsys(R) (p = 0.643 and 0.728 respectively).
      CONCLUSION: Although a generally linear relationship exists between serum S100B
      concentrations measured by ELISA and a commercially available kit, ELISA values
      tended to be higher than commercial kit measurements particularly at
      concentrations over 0.7 microg/L, which are suggestive of brain injury.
      International standardization of commercial kits is required before the
      predictive validity of S100B for brain damage can be effectively assessed in
      clinical practice.

PMID- 18803815
TI  - Scrotal abscess as a complication of perforated appendicitis: A case report and
      review of the literature.
AB  - INTRODUCTION: Abscess formation following appendectomy is well known, especially
      when complicated by perforation. Infectious complications are the most common.
      Intraabdominal abscess formation, Pelvic abscess and wound infection are the most
      common sites of infection. Scrotal abscess following acute perforated
      appendicitis is very rare. CASES PRESENTATION: We report two cases of scrotal
      abscess following perforated appendicitis, one was 1983 and the other in 1997.
      The first patient developed acute left hemiscrotum two weeks following correction
      of a tetralogy of Fallot that was diagnosed since infancy. Scrotal drainage as
      well as open appendectomy and abdominal drainage were followed by uneventful
      recovery. Six weeks later left groin exploration revealed patent processus
      vaginalis which was ligated. The second patient developed redness, swelling and
      pain in his left hemiscrotum 10 days after open appendectomy for perforated
      appendicitis. Groin exploration, ligation of a PPV and scrotal drainage was made.
      Recent reports on the subject, review of the literature, the rarity of the
      complication, and the possible association with recent introduction of
      laparoscopic appendectomy. CONCLUSION: Acute scrotal swelling is frequently a
      surgical emergency. Developing in the post-operative period is no exception.
      Symptoms and signs may be hampered by analgesia, pain, and antibiotics, usually
      administered in this period. Reporting these rare complications following such a
      common procedure, especially now a day in the era of laparoscopic surgery. Only
      high degree of suspicion and vigilant intervention will accomplish a safe
      diagnosis and treatment. The appropriate time and approach to both abscess and
      PPV is still controversial. Until enough case reports treatment is to be
      individualized.

PMID- 18803816
TI  - Neuronal hypoxia in vitro: investigation of therapeutic principles of HUCB-MNC
      and CD133+ stem cells.
AB  - BACKGROUND: The therapeutic capacity of human umbilical cord blood mononuclear
      cells (HUCB-MNC) and stem cells derived thereof is documented in animal models of
      focal cerebral ischemia, while mechanisms behind the reduction of lesion size and
      the observed improvement of behavioral skills still remain poorly understood.
      METHODS: A human in vitro model of neuronal hypoxia was used to address the
      impact of total HUCB-MNC (tMNC), a stem cell enriched fraction (CD133+, 97.38%
      CD133-positive cells) and a stem cell depleted fraction (CD133-, 0.06% CD133
      positive cells) of HUCB-MNC by either direct or indirect co-cultivation with post
      hypoxic neuronal cells (differentiated SH-SY5Y). Over three days, development of
      apoptosis and necrosis of neuronal cells, chemotaxis of MNC and production of
      chemokines (CCL2, CCL3, CCL5, CXCL8, CXCL9) and growth factors (G-CSF, GM-CSF,
      VEGF, bFGF) were analyzed using fluorescence microscopy, FACS and cytometric bead
      array. RESULTS: tMNC, CD133+ and surprisingly CD133- reduced neuronal apoptosis
      in direct co-cultivations significantly to levels in the range of normoxic
      controls (7% +/- 3%). Untreated post-hypoxic control cultures showed apoptosis
      rates of 85% +/- 11%. tMNC actively migrated towards injured neuronal cells. Both
      co-cultivation types using tMNC or CD133- reduced apoptosis comparably. CD133-
      produced high concentrations of CCL3 and neuroprotective G-CSF within indirect co
      cultures. Soluble factors produced by CD133+ cells were not detectable in direct
      co-cultures. CONCLUSION: Our data show that heterogeneous tMNC and even CD133
      depleted fractions have the capability not only to reduce apoptosis in neuronal
      cells but also to trigger the retaining of neuronal phenotypes.

PMID- 18803817
TI  - Succesful treatment of food allergy with Nambudripad's Allergy Elimination
      Techniques (NAET) in a 3-year old: A case report.
AB  - Food allergy may constitute a major burden to children and their families. A 3
      year-old girl was intolerant to milk, sugar, egg white, pork meat, and other
      foods, causing eczema and dyspnoe. She was treated with Nambudripad's Allergy
      Elimnation Technique (NAET), a combination of kinesiology and acupressure. After
      7 treatment sessions (within 4 weeks) she was free of symptoms. After three
      years, she can still eat everything without symptoms. This case report highlights
      the possible benefit of NAET for children with food allergy. Randomized clinical
      trials should be encouraged to study the effectiveness of NAET in treating food
      allergy.

PMID- 18803818
TI  - Gas emission during laparoscopic colorectal surgery using a bipolar vessel
      sealing device: A pilot study on four patients.
AB  - BACKGROUND: Dissection during laparoscopic surgery produces smoke containing
      potentially toxic substances. The aim of the present study was to analyze smoke
      samples produced during laparoscopic colon surgery using a bipolar vessel sealing
      device (LigaSuretrade mark). METHODS: Four consecutive patients undergoing left
      sided colectomy were enrolled in this pilot study. Smoke was produced by the use
      of LigaSuretrade mark. Samples (5,5l) were evacuated from the pneumoperitoneum in
      a closed system into a reservoir. Analysis was performed with CO2-laser-based
      photoacoustic spectroscopy and confirmed by a Fourier-transform infrared
      spectrum. The detected spectra were compared to the available spectra of known
      toxins. RESULTS: Samples from four laparoscopic sigmoid resections were analyzed.
      No relevant differences were noted regarding patient and operation
      characteristics. The gas samples were stable over time proven by congruent
      control measurements as late as 24 h after sampling. The absorption spectra
      differed considerably between the patients. One broad absorption line at 100 ppm
      indicating H2O and several unknown molecules were detected. With a sensitivity of
      alpha min ca 10-5 cm-1 no known toxic substances like phenol or indole were
      identified. CONCLUSION: The use of a vessel sealing device during laparoscopic
      surgery does not produce known toxic substances in relevant quantity. Further
      studies are needed to identify unknown molecules and to analyze gas emission
      under various conditions.

PMID- 18803819
TI  - A first survey of the rye (Secale cereale) genome composition through BAC end
      sequencing of the short arm of chromosome 1R.
AB  - BACKGROUND: Rye (Secale cereale L.) belongs to tribe Triticeae and is an
      important temperate cereal. It is one of the parents of man-made species
      Triticale and has been used as a source of agronomically important genes for
      wheat improvement. The short arm of rye chromosome 1 (1RS), in particular is rich
      in useful genes, and as it may increase yield, protein content and resistance to
      biotic and abiotic stress, it has been introgressed into wheat as the 1BL.1RS
      translocation. A better knowledge of the rye genome could facilitate rye
      improvement and increase the efficiency of utilizing rye genes in wheat breeding.
      RESULTS: Here, we report on BAC end sequencing of 1,536 clones from two 1RS
      specific BAC libraries. We obtained 2,778 (90.4%) useful sequences with a
      cumulative length of 2,032,538 bp and an average read length of 732 bp. These
      sequences represent 0.5% of 1RS arm. The GC content of the sequenced fraction of
      1RS is 45.9%, and at least 84% of the 1RS arm consists of repetitive DNA. We
      identified transposable element junctions in BESs and developed insertion site
      based polymorphism markers (ISBP). Out of the 64 primer pairs tested, 17 (26.6%)
      were specific for 1RS. We also identified BESs carrying microsatellites suitable
      for development of 1RS-specific SSR markers. CONCLUSION: This work demonstrates
      the utility of chromosome arm-specific BAC libraries for targeted analysis of
      large Triticeae genomes and provides new sequence data from the rye genome and
      molecular markers for the short arm of rye chromosome 1.

PMID- 18803820
TI  - Expression and regulation of transcript for the novel transmembrane protein
      Tmem182 in the adipocyte and muscle lineage.
AB  - BACKGROUND: White adipose tissue is not only an energy storage organ; it also
      functions as an endocrine organ. The coordination and integration of numerous
      gene expression events is required to establish and maintain the adipocyte
      phenotype. FINDINGS: We previously observed a 45-fold upregulation for a
      transcript encoding a novel predicted transmembrane protein, Tmem182, upon brown
      preadipocyte to adipocyte conversion. Here we use real-time PCR analysis to
      further characterize Tmem182 transcript expression in the adipocyte lineage.
      Analysis across a panel of 10 murine tissues revealed highest Tmem182 transcript
      expression in white adipose tissues (WAT), with 10-fold to 20-fold higher levels
      than in brown adipose tissue (BAT). Tmem182 transcript expression is ~3-fold
      upregulated in BAT of genetically obese (ob/ob) mice vs. wild type C57BL/6.
      Analysis of three in vitro models of white adipogenesis indicates markedly
      enriched expression of Tmem182 transcript in adipocytes vs. preadipocytes.
      Compared to 3T3-L1 preadipocytes, a 157-fold higher level of Tmem182 transcript
      is detected at 3 day post-induction of adipogenesis and an ~2500-fold higher
      level in mature 3T3-L1 adipocytes. TNFalpha treatment of 3T3-L1 adipocytes
      resulted in a ~90% decrease in Tmem182 transcript level. As skeletal muscle and
      heart were also found to express Tmem182 transcript, we assessed expression in
      C2C12 myogenesis and observed a ~770-fold upregulation upon conversion of
      myoblasts to myocytes. CONCLUSION: WAT is the most prominent site of Tmem182
      transcript expression and levels of transcript for Tmem182 are altered in adipose
      tissues of ob/ob mice and upon exposure of 3T3-L1 adipocytes to the
      proinflammatory cytokine TNFalpha. The dramatic upregulation of Tmem182
      transcript during in vitro adipogenesis and myogenesis suggests Tmem182 may
      function in intracellular pathways important in these two cell types.

PMID- 18803821
TI  - Clavicular stress fracture in a cricket fast bowler: a case report.
AB  - INTRODUCTION: Whilst rare, stress fractures of the clavicle have been described
      in other sports. To our knowledge, this is the first reported case of a stress
      fracture of the clavicle occurring in a cricket fast bowler. CASE PRESENTATION: A
      23-year-old professional cricket fast bowler presented with activity related
      shoulder pain. Imaging demonstrated a stress fracture of the lateral third of the
      clavicle. This healed with rest and rehabilitation allowing a full return to
      professional sport. CONCLUSION: This injury is treated with activity modification
      and technique adaptation. In a professional sportsman, this needs to be
      recognised early so that return to play can be as quick as possible.

PMID- 18803822
TI  - The effect of facial muscle contractions on the cerebral state index in an ICU
      patient: A case report.
AB  - INTRODUCTION: Cerebral state monitor is a monitor which shows depth of anesthesia
      in a number between 0-100 as cerebral state index, in which 40-60 is appropriate
      for general anesthesia. The effect of electromyogram on cerebral state index has
      not been shown yet. CASE REPORT: A 24-year-old Iranian-balooch man admitted in
      the intensive care unit because of head injury in a car accident. In spite of
      sustained low level of consciousness, his cerebral state index had significant
      fluctuations coordinated with electromyogram resulted from facial muscle
      contractions. After neuromuscular blocking agent prescription, cerebral state
      index was decreased from about 90 to 40, directly followed the changes in
      electromyogram.

PMID- 18803823
TI  - Delay in admission for elective coronary-artery bypass grafting is associated
      with increased in-hospital mortality.
AB  - BACKGROUND: Many health care systems now use priority wait lists for scheduling
      elective coronary artery bypass grafting (CABG) surgery, but there have not yet
      been any direct estimates of reductions in in-hospital mortality rate afforded by
      ensuring that the operation is performed within recommended time periods.
      METHODS: We used a population-based registry to identify patients with
      established coronary artery disease who underwent isolated CABG in British
      Columbia, Canada. We studied whether postoperative survival during hospital
      admission for CABG differed significantly among patients who waited for surgery
      longer than the recommended time, 6 weeks for patients needing semi-urgent
      surgery and 12 weeks for those needing non-urgent surgery. RESULTS: Among 7316
      patients who underwent CABG, 97 died during the same hospital admission, for a
      province-wide death rate at discharge of 1.3%. The observed proportion of
      patients who died during the same admission was 1.0% (27 deaths among 2675
      patients) for patients treated within the recommended time and 1.5% (70 among
      4641) for whom CABG was delayed. After adjustment for age, sex, anatomy,
      comorbidity, calendar period, hospital, and mode of admission, patients with
      early CABG were only 2/3 as likely as those for whom CABG was delayed to
      experience in-hospital death (odds ratio 0.61; 95% confidence interval [CI] 0.39
      to 0.96). There was a linear trend of 5% increase in the odds of in-hospital
      death for every additional month of delay before surgery, adjusted OR = 1.05 (95%
      CI 1.00 to 1.11). CONCLUSION: We found a significant survival benefit from
      performing surgical revascularization within the time deemed acceptable to
      consultant surgeons for patients requiring the treatment on a semi-urgent or non
      urgent basis.

PMID- 18803824
TI  - Role of IFN-gamma and IL-6 in a protective immune response to Yersinia
      enterocolitica in mice.
AB  - BACKGROUND: Yersinia outer protein (Yop) H is a secreted virulence factor of
      Yersinia enterocolitica (Ye), which inhibits phagocytosis of Ye and contributes
      to the virulence of Ye in mice. The aim of this study was to address whether and
      how YopH affects the innate immune response to Ye in mice. RESULTS: For this
      purpose, mice were infected with wild type Ye (pYV+) or a YopH-deficient Ye
      mutant strain (DeltayopH). CD11b+ cells were isolated from the infected spleen
      and subjected to gene expression analysis using microarrays. Despite the
      attenuation of DeltayopH in vivo, by variation of infection doses we were able to
      achieve conditions that allow comparison of gene expression in pYV+ and DeltayopH
      infection, using either comparable infection courses or splenic bacterial burden.
      Gene expression analysis provided evidence that expression levels of several
      immune response genes, including IFN-gamma and IL-6, are high after pYV+
      infection but low after sublethal DeltayopH infection. In line with these
      findings, infection of IFN-gammaR-/- and IL-6-/- mice with pYV+ or DeltayopH
      revealed that these cytokines are not necessarily required for control of
      DeltayopH, but are essential for defense against infection with the more virulent
      pYV+. Consistently, IFN-gamma pretreatment of bone marrow derived macrophages
      (BMDM) strongly enhanced their ability in killing intracellular Ye bacteria.
      CONCLUSION: In conclusion, this data suggests that IFN-gamma-mediated effector
      mechanisms can partially compensate virulence exerted by YopH. These results shed
      new light on the protective role of IFN-gamma in Ye wild type infections.

PMID- 18803825
TI  - Paroxysmal extreme pain disorder M1627K mutation in human Nav1.7 renders DRG
      neurons hyperexcitable.
AB  - BACKGROUND: Paroxysmal extreme pain disorder (PEPD) is an autosomal dominant
      painful neuropathy with many, but not all, cases linked to gain-of-function
      mutations in SCN9A which encodes voltage-gated sodium channel Nav1.7. Severe pain
      episodes and skin flushing start in infancy and are induced by perianal probing
      or bowl movement, and pain progresses to ocular and mandibular areas with age.
      Carbamazepine has been effective in relieving symptoms, while other drugs
      including other anti-epileptics are less effective. RESULTS: Sequencing of SCN9A
      coding exons from an English patient, diagnosed with PEPD, has identified a
      methionine 1627 to lysine (M1627K) substitution in the linker joining segments S4
      and S5 in domain IV. We confirm that M1627K depolarizes the voltage-dependence of
      fast-inactivation without substantially altering activation or slow-inactivation,
      and inactivates from the open state with slower kinetics. We show here that
      M1627K does not alter development of closed-state inactivation, and that M1627K
      channels recover from fast-inactivation faster than wild type channels, and
      produce larger currents in response to a slow ramp stimulus. Using current-clamp
      recordings, we also show that the M1627K mutant channel reduces the threshold for
      single action potentials in DRG neurons and increases the number of action
      potentials in response to graded stimuli. CONCLUSION: M1627K mutation was
      previously identified in a sporadic case of PEPD from France, and we now report
      it in an English family. We confirm the initial characterization of mutant M1627K
      effect on fast-inactivation of Nav1.7 and extend the analysis to other gating
      properties of the channel. We also show that M1627K mutant channels render DRG
      neurons hyperexcitable. Our new data provide a link between altered channel
      biophysics and pain in PEPD patients.

PMID- 18803826
TI  - The VEPRO trial: a cross-over randomised controlled trial comparing 2 progressive
      lenses for patients with presbyopia.
AB  - The aim of this trial was to compare the effectiveness of two generations of
      progressive lenses for presbyopia. METHODS: A multicenter cross-over randomized
      controlled trial performed in a primary care setting (5 optical dispensaries) was
      planned. Two categories of progressive lenses were compared: 1) a new-generation
      lens (i.e., VARILUX PANAMIC ORMA CRIZAL), which is expensive but a supposed
      improvement in comfort, and 2) an older-generation lens (i.e., VARILUX CONFORT
      ORMA CRIZAL), which is less expensive and is considered the reference lens.
      Patients were randomized to wear one generation of progressive lens for 4 weeks,
      then cross over to wear the other lens for 4 weeks, without knowing the sequence
      of lenses. Inclusion criteria were 1) age 43-60 years; 2) outpatients already
      wearing progressive lenses and referred to an optician ophthalmologist for
      optical correction prescription within the last 6 months; 3) receiving a
      correction of </=3 dioptres in cases of associated myopia, hyperopia or
      astigmatism; 4) understanding and speaking French and able to answer a
      questionnaire; and 5) giving written consent to participate in the study.The
      primary outcome was patient preference for one progressive lens at week 8.
      Secondary outcomes were subjective measures of bifocal visual performance,
      including a) near visual acuity, b) visual field, c) kinetic visual skills, d)
      visual adaptability, e) visual comfort, and f) rapidity of adaptation. RESULTS:
      127 patients were randomized to one of the lens groups. Two patients withdrew
      prematurely; 98.4% and 97.6% patients who wore the new versus older lenses,
      respectively, wore their progressive lenses every day during the 4-week period 1
      and period 2. The number of participants in each of 5 centres varied from 16
      (12.6%) to 35 (27.6%).57.9% patients preferred the new-generation lenses, 36.5%
      the older-generation lenses, and 5.6% had no preference (p = 0.01). The two
      groups did not differ in any of the measures of bifocal visual performance except
      near visual acuity. CONCLUSION: Patients with presbyopia had slightly higher
      preference for the new-generation than older-generation lens, with no difference
      in lens groups for most of the visual outcomes assessed. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT00635115.

PMID- 18803827
TI  - Adaptation costs for climate change-related cases of diarrhoeal disease,
      malnutrition, and malaria in 2030.
AB  - BACKGROUND: Climate change has begun to negatively affect human health, with
      larger burdens projected in the future as weather patterns continue to change.
      The climate change-related health consequences of diarrhoeal diseases,
      malnutrition, and malaria are projected to pose the largest risks to future
      populations. Limited work has been done to estimate the costs of adapting to
      these additional health burdens. METHODS: The costs of treating diarrhoeal
      diseases, malnutrition (stunting and wasting only), and malaria in 2030 were
      estimated under three climate scenarios using (1) the current numbers of cases;
      (2) the projected relative risks of these diseases in 2030; and (3) current
      treatment costs. The analysis assumed that the number of annual cases and costs
      of treatment would remain constant. There was limited consideration of
      socioeconomic development. RESULTS: Under a scenario assuming emissions
      reductions resulting in stabilization at 750 ppm CO2 equivalent in 2210, the
      costs of treating diarrhoeal diseases, malnutrition, and malaria in 2030 were
      estimated to be $4 to 12 billion. This is almost as much as current total annual
      overseas development assistance for health. CONCLUSION: The investment needs in
      the health sector to address climate-sensitive health outcomes are large.
      Additional human and financial resources will be needed to prevent and control
      the projected increased burden of health outcomes due to climate change.

PMID- 18803828
TI  - Visualizing the actin cytoskeleton in living plant cells using a photo
      convertible mEos::FABD-mTn fluorescent fusion protein.
AB  - BACKGROUND: The actin cytoskeleton responds quickly to diverse stimuli and plays
      numerous roles in cellular signalling, organelle motility and subcellular
      compartmentation during plant growth and development. Molecular and cell
      biological tools that can facilitate visualization of actin organization and
      dynamics in a minimally invasive manner are essential for understanding this
      fundamental component of the living cell. RESULTS: A novel, monomeric (m) Eos
      fluorescent protein derived from the coral Lobophyllia hemprichii was assessed
      for its green to red photo-convertibility in plant cells by creating mEosFP
      cytosolic. mEosFP was fused to the F-(filamentous)-Actin Binding Domain of the
      mammalian Talin gene to create mEosFP::FABDmTalin. Photo-conversion,
      visualization and colour quantification protocols were developed for EosFP
      targeted to the F-actin cytoskeleton. Rapid photo-conversion in the entire cell
      or in a region of interest was easily achieved upon illumination with an
      approximately 400 nm wavelength light beam using an epi-fluorescent microscope.
      Dual color imaging after photo-conversion was carried out using a confocal laser
      scanning microscope. Time-lapse imaging revealed that although photo-conversion
      of single mEosFP molecules can be rapid in terms of live-cell imaging it involves
      a progressive enrichment of red fluorescent molecules over green species. The
      fluorescence of photo-converted cells thus progresses through intermediate shades
      ranging from green to red. The time taken for complete conversion to red
      fluorescence depends on protein expression level within a cell and the quality of
      the focusing lens used to deliver the illuminating beam. Three easily applicable
      methods for obtaining information on fluorescent intensity and colour are
      provided as a means of ensuring experimental repeatability and data
      quantification, when using mEosFP and similar photo-convertible proteins.
      CONCLUSION: The mEosFP::FABD-mTn probe retains all the imaging qualities
      associated with the well tested GFP::mTn probe while allowing for non-invasive,
      regional photo-conversion that allows colour based discrimination within a living
      cell. Whereas a number of precautions should be exercised in dealing with photo
      convertible probes, mEosFP::FABD-mTn is a versatile live imaging tool for
      dissecting the organization and activity of the actin cytoskeleton in plants.

PMID- 18803829
TI  - The design, development, and evaluation of a prototypic, prosthetic venous valve.
AB  - BACKGROUND: Chronic venous insufficiency is a serious disease for which there is
      no clearly successful surgical treatment. Availability of a proven prosthetic
      vein valve could provide such an option by reducing venous reflux while
      permitting normal antegrade flow. METHODS: A new prosthetic vein valve design has
      been developed which mimics the function of a natural valve by ensuring complete
      closure of the leaflets with minimal obstruction for antegrade flow. A 2:1 mock
      up of the device was tested to evaluate its ability to prevent regurgitation and
      several key modifications were made. A subsequently re-designed 1:1 prototype was
      then built in 4 slightly different size configurations and then each tested under
      physiologic conditions of pulsatile flow in both supine and standing positions.
      RESULTS: Each of the configurations showed acceptable amounts of antegrade
      resistance and effective orifice area and showed low values of regurgitation and
      % reflux with two of the prototype configurations (flange lengths of 2.5 mm and
      3.75 mm) having corresponding values of <2.5 mmHg-min/L, >97%, 11 mL, and 36%,
      respectively. These values are particularly striking when compared to the
      corresponding regurgitation and % reflux values of 60 mL and 205%, respectively,
      when no device is present. CONCLUSION: The results of this study show that this
      prototype vein valve design is capable of providing significant relief of reflux
      under realistic conditions without inducing any increase in antegrade flow
      resistance and warrants further testing with in vivo models.

PMID- 18803830
TI  - GlycomeDB - integration of open-access carbohydrate structure databases.
AB  - BACKGROUND: Although carbohydrates are the third major class of biological
      macromolecules, after proteins and DNA, there is neither a comprehensive database
      for carbohydrate structures nor an established universal structure encoding
      scheme for computational purposes. Funding for further development of the Complex
      Carbohydrate Structure Database (CCSD or CarbBank) ceased in 1997, and since then
      several initiatives have developed independent databases with partially
      overlapping foci. For each database, different encoding schemes for residues and
      sequence topology were designed. Therefore, it is virtually impossible to obtain
      an overview of all deposited structures or to compare the contents of the various
      databases. RESULTS: We have implemented procedures which download the structures
      contained in the seven major databases, e.g. GLYCOSCIENCES.de, the Consortium for
      Functional Glycomics (CFG), the Kyoto Encyclopedia of Genes and Genomes (KEGG)
      and the Bacterial Carbohydrate Structure Database (BCSDB). We have created a new
      database called GlycomeDB, containing all structures, their taxonomic annotations
      and references (IDs) for the original databases. More than 100000 datasets were
      imported, resulting in more than 33000 unique sequences now encoded in GlycomeDB
      using the universal format GlycoCT. Inconsistencies were found in all public
      databases, which were discussed and corrected in multiple feedback rounds with
      the responsible curators. CONCLUSION: GlycomeDB is a new, publicly available
      database for carbohydrate sequences with a unified, all-encompassing structure
      encoding format and NCBI taxonomic referencing. The database is updated weekly
      and can be downloaded free of charge. The JAVA application GlycoUpdateDB is also
      available for establishing and updating a local installation of GlycomeDB. With
      the advent of GlycomeDB, the distributed islands of knowledge in glycomics are
      now bridged to form a single resource.

PMID- 18803831
TI  - Construction and validation of a dimensional scale exploring mood disorders:
      MAThyS (Multidimensional Assessment of Thymic States).
AB  - BACKGROUND: The boundaries between mood states in bipolar disorders are not clear
      when they are associated with mixed characteristics. This leads to some confusion
      to define appropriate therapeutic strategies. A dimensional approach might help
      to better define bipolar moods states and more specifically those with mixed
      features. Therefore, we proposed a new tool based on a dimensional approach,
      built with a priori five sub-scales and focus on emotional reactivity rather than
      exclusively on mood tonality. This study was designed to validate this MAThyS
      Scale (Multidimensional Assessment of Thymic States). METHODS: One hundred and
      ninety six subjects were included: 44 controls and 152 bipolar patients in
      various states: euthymic, manic or depressed. The MAThyS is a visual analogic
      scale consisting of 20 items. These items corresponded to five quantitative
      dimensions ranging from inhibition to excitation: emotional reactivity, thought
      processes, psychomotor function, motivation and sensory perception. They were
      selected as they represent clinically relevant quantitative traits. RESULTS:
      Confirmatory analyses demonstrated a good validity for this scale, and a good
      internal consistency (Cronbach's alpha coefficient = 0.95). The MathyS scale is
      moderately correlated of both the MADRS scale (depressive score; r = -0.45) and
      the MAS scale (manic score; r = 0.56). When considering the Kaiser-Guttman rule
      and the scree plot, our model of 5 factors seems to be valid. The four first
      factors have an eigenvalue greater than 1.0 and the eigenvalue of the factor five
      is 0.97. In the scree plot, the "elbow", or the point at which the curve bends,
      indicates 5 factors to extract. This 5 factors structure explains 68 per cent of
      variance. CONCLUSION: The characterisation of bipolar mood states based on a
      global score assessing inhibition/activation process (total score of the MATHyS)
      associated with descriptive analysis on sub-scores such as emotional reactivity
      (rather than the classical opposition euphoria/sadness) can be useful to better
      understand the broad spectrum of mixed states.

PMID- 18803832
TI  - Role of STAT4 polymorphisms in systemic lupus erythematosus in a Japanese
      population: a case-control association study of the STAT1-STAT4 region.
AB  - INTRODUCTION: Recent studies identified STAT4 (signal transducers and activators
      of transcription-4) as a susceptibility gene for systemic lupus erythematosus
      (SLE). STAT1 is encoded adjacently to STAT4 on 2q32.2-q32.3, upregulated in
      peripheral blood mononuclear cells from SLE patients, and functionally relevant
      to SLE. This study was conducted to test whether STAT4 is associated with SLE in
      a Japanese population also, to identify the risk haplotype, and to examine the
      potential genetic contribution of STAT1. To accomplish these aims, we carried out
      a comprehensive association analysis of 52 tag single nucleotide polymorphisms
      (SNPs) encompassing the STAT1-STAT4 region. METHODS: In the first screening, 52
      tag SNPs were selected based on HapMap Phase II JPT (Japanese in Tokyo, Japan)
      data, and case-control association analysis was carried out on 105 Japanese
      female patients with SLE and 102 female controls. For associated SNPs, additional
      cases and controls were genotyped and association was analyzed using 308 SLE
      patients and 306 controls. Estimation of haplotype frequencies and an association
      study using the permutation test were performed with Haploview version 4.0
      software. Population attributable risk percentage was estimated to compare the
      epidemiological significance of the risk genotype among populations. RESULTS: In
      the first screening, rs7574865, rs11889341, and rs10168266 in STAT4 were most
      significantly associated (P < 0.01). Significant association was not observed for
      STAT1. Subsequent association studies of the three SNPs using 308 SLE patients
      and 306 controls confirmed a strong association of the rs7574865T allele (SLE
      patients: 46.3%, controls: 33.5%, P = 4.9 x 10(-6), odds ratio 1.71) as well as
      TTT haplotype (rs10168266/rs11889341/rs7574865) (P = 1.5 x 10(-6)). The
      association was stronger in subgroups of SLE with nephritis and anti-double
      stranded DNA antibodies. Population attributable risk percentage was estimated to
      be higher in the Japanese population (40.2%) than in Americans of European
      descent (19.5%). CONCLUSIONS: The same STAT4 risk allele is associated with SLE
      in Caucasian and Japanese populations. Evidence for a role of STAT1 in genetic
      susceptibility to SLE was not detected. The contribution of STAT4 for the genetic
      background of SLE may be greater in the Japanese population than in Americans of
      European descent.

PMID- 18803833
TI  - Malaria case-management under artemether-lumefantrine treatment policy in Uganda.
AB  - BACKGROUND: Case-management with artemether-lumefantrine (AL) is one of the key
      strategies to control malaria in many African countries. Yet, the reports on
      translation of AL implementation activities into clinical practice are scarce.
      Here the quality of AL case-management is reported from Uganda; approximately one
      year after AL replaced combination of chloroquine and sulphadoxine-pyrimethamine
      (CQ+SP) as recommended first line treatment for uncomplicated malaria. METHODS: A
      cross-sectional survey, using a range of quality of care assessment tools, was
      undertaken at all government and private-not-for-profit facilities in four
      Ugandan districts. Main outcome measures were AL prescribing, dispensing and
      counseling practices in comparison with national guidelines, and factors
      influencing health workers decision to 1) treat for malaria, and 2) prescribe AL.
      RESULTS: 195 facilities, 232 health workers and 1,763 outpatient consultations
      were evaluated. Of 1,200 patients who needed treatment with AL according to
      guidelines, AL was prescribed for 60%, CQ+SP for 14%, quinine for 4%, CQ for 3%,
      other antimalarials for 3%, and 16% of patients had no antimalarial drug
      prescribed. AL was prescribed in the correct dose for 95% of patients. Only three
      out of seven AL counseling and dispensing tasks were performed for more than 50%
      of patients. Patients were more likely to be treated for malaria if they
      presented with main complaint of fever (OR = 5.22; 95% CI: 3.61-7.54) and if they
      were seen by supervised health workers (OR = 1.63; 95% CI: 1.06-2.50); however
      less likely if they were treated by more qualified health workers (OR = 0.61; 95%
      CI: 0.40-0.93) and presented with skin problem (OR = 0.29; 95% CI: 0.15-0.55). AL
      was more likely prescribed if the appropriate weight-specific AL pack was in
      stock (OR = 6.15; 95% CI: 3.43-11.05) and when CQ was absent (OR = 2.16; 95% CI:
      1.09-4.28). Routine AL implementation activities were not associated with better
      performance. CONCLUSION: Although the use of AL was predominant over non
      recommended therapies, the quality of AL case-management at the point of care is
      not yet optimal. There is an urgent need for innovative quality improvement
      interventions, which should be rigorously tested. Adequate availability of ACTs
      at the point of care will, however, ultimately determine the success of any
      performance interventions and ACT policy transitions.

PMID- 18803834
TI  - Posterior dislocation of the elbow associated with fracture of the radial head
      and olecranon, and with medial collateral ligament disruption: A case report.
AB  - INTRODUCTION: Fracture dislocations of the elbow appear extremely complex.
      Identification of the basic injury patterns can facilitate management. CASE
      PRESENTATION: A 38-year-old male motor-vehicle driver who fell on his right elbow
      after an accident was suffering from posterior dislocation of the elbow, without
      coronoid fracture, and with fracture of the radial head and olecranon, and medial
      collateral ligament disruption, which was not associated with any vascular or
      neural injury. CONCLUSION: Posterior dislocation of the elbow associated with
      fracture of the radial head and olecranon, and medial collateral ligament
      disruption may be a rare subgroup of elbow dislocation. We should pay more
      attention to medial collateral ligament injury with elbow dislocation.

PMID- 18803835
TI  - Phylogenetic and chromosomal analyses of multiple gene families syntenic with
      vertebrate Hox clusters.
AB  - BACKGROUND: Ever since the theory about two rounds of genome duplication (2R) in
      the vertebrate lineage was proposed, the Hox gene clusters have served as the
      prime example of quadruplicate paralogy in mammalian genomes. In teleost fishes,
      the observation of additional Hox clusters absent in other vertebrate lineages
      suggested a third tetraploidization (3R). Because the Hox clusters occupy a quite
      limited part of each chromosome, and are special in having position-dependent
      regulation within the multi-gene cluster, studies of syntenic gene families are
      needed to determine the extent of the duplicated chromosome segments. We have
      analyzed in detail 14 gene families that are syntenic with the Hox clusters to
      see if their phylogenies are compatible with the Hox duplications and the 2R/3R
      scenario. Our starting point was the gene family for the NPY family of peptides
      located near the Hox clusters in the pufferfish Takifugu rubripes, the zebrafish
      Danio rerio, and human. RESULTS: Seven of the gene families have members on at
      least three of the human Hox chromosomes and two families are present on all
      four. Using both neighbor-joining and quartet-puzzling maximum likelihood methods
      we found that 13 families have a phylogeny that supports duplications coinciding
      with the Hox cluster duplications. One additional family also has a topology
      consistent with 2R but due to lack of urochordate or cephalochordate sequences
      the time window when these duplications could have occurred is wider. All but two
      gene families also show teleost-specific duplicates. CONCLUSION: Based on this
      analysis we conclude that the Hox cluster duplications involved a large number of
      adjacent gene families, supporting expansion of these families in the 2R, as well
      as in the teleost 3R tetraploidization. The gene duplicates presumably provided
      raw material in early vertebrate evolution for neofunctionalization and
      subfunctionalization.

PMID- 18803836
TI  - Improving peptide-MHC class I binding prediction for unbalanced datasets.
AB  - BACKGROUND: Establishment of peptide binding to Major Histocompatibility Complex
      class I (MHCI) is a crucial step in the development of subunit vaccines and
      prediction of such binding could greatly reduce costs and accelerate the
      experimental process of identifying immunogenic peptides. Many methods have been
      applied to the prediction of peptide-MHCI binding, with some achieving
      outstanding performance. Because of the experimental methods used to measure
      binding or affinity between peptides and MHCI molecules, however, available
      datasets are enriched for nonbinders, and thus highly unbalanced. Although there
      is no consensus on the ideal class distribution for training sets, extremely
      unbalanced datasets can be detrimental to the performance of prediction
      algorithms. RESULTS: We have developed a decision-theoretic framework to
      construct cost-sensitive trees to predict peptide-MHCI binding and have used them
      to 1) Assess the impact of the training data's class distribution on classifier
      accuracy, and 2) Compare resampling and cost-sensitive methods as approaches to
      compensate for training data imbalance. Our results confirm that highly
      unbalanced training sets can reduce the accuracy of classifier predictions and
      show that, in the peptide-MHCI binding context, resampling methods do not improve
      the classifier performance. In contrast, cost-sensitive methods significantly
      improve accuracy of decision trees. Finally, we propose the use of a training
      scheme that, when the training set is enriched for nonbinders, consistently
      improves the overall classifier accuracy compared to cost-insensitive classifiers
      and, in particular, increases the sensitivity of the classifiers. This method
      minimizes the expected classification cost for large datasets. CONCLUSION: Our
      method consistently improves the performance of decision trees in predicting
      peptide-MHC class I binding by using cost-balancing techniques to compensate for
      the imbalance in the training dataset.

PMID- 18803837
TI  - Myogenesis in the basal bilaterian Symsagittifera roscoffensis (Acoela).
AB  - BACKGROUND: In order to increase the weak database concerning the organogenesis
      of Acoela - a clade regarded by many as the earliest extant offshoot of Bilateria
      and thus of particular interest for studies concerning the evolution of animal
      bodyplans - we analyzed the development of the musculature of Symsagittifera
      roscoffensis using F-actin labelling, confocal laserscanning microscopy, and 3D
      reconstruction software. RESULTS: At 40% of development between egg deposition
      and hatching short subepidermal fibres form. Muscle fibre development in the
      anterior body half precedes myogenesis in the posterior half. At 42% of
      development a grid of outer circular and inner longitudinal muscles is present in
      the bodywall. New circular muscles either branch off from present fibres or form
      adjacent to existing ones. The number of circular muscles is higher than that of
      the longitudinal muscles throughout all life cycle stages. Diagonal, circular and
      longitudinal muscles are initially rare but their number increases with time. The
      ventral side bears U-shaped muscles around the mouth, which in addition is
      surrounded by a sphincter muscle. With the exception of the region of the
      statocyst, dorsoventral muscles are present along the entire body of juveniles
      and adults, while adults additionally exhibit radially oriented internal muscles
      in the anterior tip. Outer diagonal muscles are present at the dorsal anterior
      tip of the adult. In adult animals, the male gonopore with its associated sexual
      organs expresses distinct muscles. No specific statocyst muscles were found. The
      muscle mantles of the needle-shaped sagittocysts are situated along the lateral
      edges of the animal and in the posterior end close to the male gonopore. In both
      juveniles and adults, non-muscular filaments, which stain positively for F-actin,
      are associated with certain sensory cells outside the bodywall musculature.
      CONCLUSION: Compared to the myoanatomy of other acoel taxa, Symsagittifera
      roscoffensis shows a very complex musculature. Although data on presumably basal
      acoel clades are still scarce, the information currently available suggests an
      elaborated musculature with longitudinal, circular and U-shaped muscles as being
      part of the ancestral acoel bodyplan, thus increasing the possibility that
      Urbilateria likewise had a relatively complicated muscular ground pattern.

PMID- 18803838
TI  - Health-related quality of life in infertile couples receiving IVF or ICSI
      treatment.
AB  - BACKGROUND: Infertile couples might experience psychological distress and suffer
      from impaired health-related quality of life. This study aimed to examine health
      related quality of life in infertile couples receiving either in-vitro
      fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatment.
      METHODS: This was a cross-sectional study of quality of life in infertile couples
      attending to Vali-e-Asr Reproductive Health Research Center or Royan Institute
      for either IVF or ICSI treatment in Tehran, Iran. Health-related quality of life
      was assessed using the Short Form Health Survey (SF-36). Patients' demographic
      and clinical characteristics were also recorded. Data were analyzed to compare
      quality of life in infertile women and men and to indicate what variables predict
      quality of life in infertile couples. RESULTS: In all 514 women and 514 men (n =
      1028) were studied. There were significant differences between women and men
      indicating that male patients had a better health-related quality of life. Also
      health-related quality of life was found to be better in infertility due to male
      factor. Performing logistic regression analysis it was found that female gender,
      and lower educational level were significant predictors of poorer physical health
      related quality of life. For mental health-related quality of life in addition to
      female gender and lower educational level, younger age also was found to be a
      significant predictor of poorer condition. No significant results were observed
      for infertility duration or causes of infertility either for physical or mental
      health-related quality of life. CONCLUSION: The findings suggest that infertility
      duration or causes of infertility do not have significant effects on health
      related quality of life in infertile couples. However, infertile couples,
      especially less educated younger women, are at risk of a sub-optimal health
      related quality of life and they should be provided help and support in order to
      improve their health-related quality of life.

PMID- 18803839
TI  - Late development of esophageal stricture following radiation and chemotherapy for
      small cell carcinoma of the lung: A case report.
AB  - BACKGROUND: The development of esophageal stricture is not an uncommon side
      effect of radiation and chemotherapy for neck and thoracic malignancies.
      Depending on the study, it may occur anywhere from 2-3 weeks to 4-8 months after
      therapy. However, chronic late presentations of post-treatment stricture are
      highly atypical events. CASE PRESENTATION: The authors describe herein an unusual
      case of a 65 year old male with esophageal stricture presenting as dysphagia and
      complicated by multiple episodes of aspiration pneumonia four years after
      chemoradiation treatment for small cell carcinoma of the lung. The patient's
      symptoms were ameliorated after esophageal dilation with stenting. CONCLUSION:
      Latent esophageal stricture should be suspected in any patient previously treated
      with radiation and chemotherapy regardless of how long ago the therapy was
      initiated.

PMID- 18803840
TI  - Systematic bioinformatic analysis of expression levels of 17,330 human genes
      across 9,783 samples from 175 types of healthy and pathological tissues.
AB  - Our knowledge on tissue- and disease-specific functions of human genes is rather
      limited and highly context-specific. Here, we have developed a method for the
      comparison of mRNA expression levels of most human genes across 9,783 Affymetrix
      gene expression array experiments representing 43 normal human tissue types, 68
      cancer types, and 64 other diseases. This database of gene expression patterns in
      normal human tissues and pathological conditions covers 113 million datapoints
      and is available from the GeneSapiens website.

PMID- 18803841
TI  - False aneurysm of the radial artery: Unusual complication of both-bone forearm
      fracture in children: A case report.
AB  - False aneurysm or pseudo aneurysm of an artery in close proximity to fractured
      bone is a well-recognized entity, and fewer various cases, involving different
      sites have been reported in the literature. We report new case of a Moroccan's
      patient who had 10-year-old boy presented with a right non displaced both-bone
      forearm fracture; the patient was placed in a long arm splint. After, six weeks,
      the cast was removed. And a pulsatile mass on the volar-radial aspect of the
      forearm was decouvred. The mass was non-tender and the patient had radial and
      ulnar pulse. An Ultrasound and brachial angiography showed a false aneurysm of
      distal radial and the radial artery was ligated.In conclusion, pseudoaneurysm of
      the radial artery can be associated with any bone fracture despite non displacing
      fractures related to the elasticity of the bone in this age and orthopedic
      surgeons should be aware of this potential complication.

PMID- 18803842
TI  - Food allergy knowledge, attitudes and beliefs: focus groups of parents,
      physicians and the general public.
AB  - BACKGROUND: Food allergy prevalence is increasing in US children. Presently, the
      primary means of preventing potentially fatal reactions are avoidance of
      allergens, prompt recognition of food allergy reactions, and knowledge about food
      allergy reaction treatments. Focus groups were held as a preliminary step in the
      development of validated survey instruments to assess food allergy knowledge,
      attitudes, and beliefs of parents, physicians, and the general public. METHODS:
      Eight focus groups were conducted between January and July of 2006 in the Chicago
      area with parents of children with food allergy (3 groups), physicians (3
      groups), and the general public (2 groups). A constant comparative method was
      used to identify the emerging themes which were then grouped into key domains of
      food allergy knowledge, attitudes, and beliefs. RESULTS: Parents of children with
      food allergy had solid fundamental knowledge but had concerns about primary care
      physicians' knowledge of food allergy, diagnostic approaches, and treatment
      practices. The considerable impact of children's food allergies on familial
      quality of life was articulated. Physicians had good basic knowledge of food
      allergy but differed in their approach to diagnosis and advice about starting
      solids and breastfeeding. The general public had wide variation in knowledge
      about food allergy with many misconceptions of key concepts related to
      prevalence, definition, and triggers of food allergy. CONCLUSION: Appreciable
      food allergy knowledge gaps exist, especially among physicians and the general
      public. The quality of life for children with food allergy and their families is
      significantly affected.

PMID- 18803843
TI  - Survival of hereditary non-polyposis colorectal cancer patients compared with
      sporadic colorectal cancer patients.
AB  - BACKGROUND: Patients with hereditary non-poliposys colorectal cancer (HNPCC) have
      better prognosis than sporadic colorectal cancer (CRC). Aim of our retrospective
      study was to compare the overall survival between sporadic CRC and HNPCC
      patients. METHODS: We analyzed a cohort of 40 (25 males and 15 females) HNPCC
      cases with a hospital consecutive series of 573 (312 males and 261 females)
      sporadic CRC observed during the period 1970-1993. In 15 HNPCC patients we
      performed mutational analysis for microsatellite instability. Survival rates were
      calculated by Kaplan-Meier method and compared with log rank test. RESULTS: The
      median age at diagnosis of the primary CRC was 46.8 years in the HNPCC series
      versus 61 years in sporadic CRC group. In HNPCC group 85% had a right cancer
      location, vs. 57% in the sporadic cancer group. In the sporadic cancer group
      61.6% were early-stages cancer (Dukes' A and B) vs. 70% in the HNPCC group (p =
      ns). The crude 5-years cumulative survival after the primary CRC was 94.2% in
      HNPCC patients vs. 75.3% in sporadic cancer patients (p < 0.0001). CONCLUSION:
      Our results show that overall survival of colorectal cancer in patients with
      HNPCC is better than sporadic CRC patients. The different outcome probably
      relates to the specific tumorigenesis involving DNA mismatch repair dysfunction.

PMID- 18803844
TI  - The metagenomics RAST server - a public resource for the automatic phylogenetic
      and functional analysis of metagenomes.
AB  - BACKGROUND: Random community genomes (metagenomes) are now commonly used to study
      microbes in different environments. Over the past few years, the major challenge
      associated with metagenomics shifted from generating to analyzing sequences. High
      throughput, low-cost next-generation sequencing has provided access to
      metagenomics to a wide range of researchers. RESULTS: A high-throughput pipeline
      has been constructed to provide high-performance computing to all researchers
      interested in using metagenomics. The pipeline produces automated functional
      assignments of sequences in the metagenome by comparing both protein and
      nucleotide databases. Phylogenetic and functional summaries of the metagenomes
      are generated, and tools for comparative metagenomics are incorporated into the
      standard views. User access is controlled to ensure data privacy, but the
      collaborative environment underpinning the service provides a framework for
      sharing datasets between multiple users. In the metagenomics RAST, all users
      retain full control of their data, and everything is available for download in a
      variety of formats. CONCLUSION: The open-source metagenomics RAST service
      provides a new paradigm for the annotation and analysis of metagenomes. With
      built-in support for multiple data sources and a back end that houses abstract
      data types, the metagenomics RAST is stable, extensible, and freely available to
      all researchers. This service has removed one of the primary bottlenecks in
      metagenome sequence analysis - the availability of high-performance computing for
      annotating the data. http://metagenomics.nmpdr.org.

PMID- 18803845
TI  - Development and first assessment of a questionnaire for health care utilization
      and costs for cardiac patients.
AB  - BACKGROUND: The valid and reliable measurement of health service utilization,
      productivity losses and consequently total disease-related costs is a
      prerequisite for health services research and for health economic analysis.
      Although administrative data sources are usually considered to be the most
      accurate, their use is limited as some components of utilization are not
      systematically captured and, especially in decentralized health care systems, no
      single source exists for comprehensive utilization and cost data. The aim of this
      study was to develop and test a questionnaire for the measurement of disease
      related costs for patients after an acute cardiac event (ACE). METHODS: To design
      the questionnaire, the literature was searched for contributions to the
      assessment of utilization of health care resources by patient-administered
      questionnaires. Based on these findings, we developed a retrospective
      questionnaire appropriate for the measurement of disease-related costs over a
      period of 3 months in ACE patients. Items were generated by reviewing existing
      guidelines and by interviewing medical specialists and patients. In this study,
      the questionnaire was tested on 106 patients, aging 35-65 who were admitted for
      rehabilitation after ACE. It was compared with prospectively measured data;
      selected items were compared with administrative data from sickness funds.
      RESULTS: The questionnaire was accepted well (response rate = 88%), and
      respondents completed the questionnaire in an average time of 27 minutes.
      Concordance between retrospective and prospective data showed an intraclass
      correlation (ICC) ranging between 0.57 (cost of medical intake) and 0.9 (hospital
      days) with the other main items (physician visits, days off work, medication)
      clustering around 0.7. Comparison between self-reported and administrative data
      for days off work and hospitalized days were possible for n = 48. Respective ICCs
      ranged between 0.92 and 0.94, although differences in mean levels were observed.
      CONCLUSION: The questionnaire was accepted favorably and correlated well with
      alternative measurement approaches. This first assessment showed promising
      characteristics of this questionnaire in different aspects of validity for
      patients with ACE. However, additional research and more extensive tests in other
      patient groups would be worthwhile.

PMID- 18803846
TI  - Mediastinal lipomatosis as a cause of low voltage complexes on electrocardiogram
      and widened mediastinum: A case report.
AB  - BACKGROUND: Mediastinal widening is a common finding on chest radiograph, and can
      be caused by numerous conditions. Most of these diseases have grave prognosis if
      accompanied by chest pain, and require immediate attention. However, mediastinal
      lipomatosis is a very benign condition caused by deposition of adipose tissue in
      the mediastinum. CASE PRESENTATION: We present a case of a morbidly obese female
      patient who presented to emergency department with a fall. She had mediastinal
      widening on chest radiograph, and borderline low voltage on electrocardiogram. On
      computed tomography, mediastinal lipomatosis was evident. CONCLUSION: Obesity is
      a major epidemic in United States, and can lead to deposition of fat in the
      chest. Mediastinal lipomatosis is very benign condition, which rarely causes
      grave consequences.

PMID- 18803847
TI  - Transcriptional regulation of mouse alpha A-crystallin gene in a 148kb Cryaa BAC
      and its derivates.
AB  - BACKGROUND: alphaA-crystallin is highly expressed in the embryonic, neonatal and
      adult mouse lens. Previously, we identified two novel distal control regions,
      DCR1 and DCR3. DCR1 was required for transgenic expression of enhanced green
      fluorescent protein, EGFP, in lens epithelium, whereas DCR3 was active during
      "late" stages of lens primary fiber cell differentiation. However, the onset of
      transgenic EGFP expression was delayed by 12-24 hours, compared to the expression
      of the endogenous Cryaa gene. RESULTS: Here, we used bacterial artificial
      chromosome (BAC) and standard transgenic approaches to examine temporal and
      spatial regulation of the mouse Cryaa gene. Two BAC transgenes, with EGFP
      insertions into the third coding exon of Cryaa gene, were created: the intact
      alphaA-crystallin 148 kb BAC (alphaA-BAC) and alphaA-BAC(DeltaDCR3), which lacks
      approximately 1.0 kb of genomic DNA including DCR3. Expression of EGFP in the
      majority of both BAC transgenics nearly recapitulated the endogenous expression
      pattern of the Cryaa gene in lens, but not outside of the lens. The number of
      cells expressing alphaA-crystallin in the lens pit was higher compared to the
      number of cells expressing EGFP. Next, we generated additional lines using a 15
      kb fragment of alphaA-crystallin locus derived from alphaA-BAC(DeltaDCR3), 15 kb
      Cryaa/EGFP. A 15 kb region of Cryaa/EGFP supported the expression pattern of EGFP
      also in the lens pit. However, co-localization studies of alphaA-crystallin and
      EGFP indicated that the number of cells that showed transgenic expression was
      higher compared to cells expressing alphaA-crystallin in the lens pit.
      CONCLUSION: We conclude that a 148 kb alphaA-BAC likely contains all of the
      regulatory regions required for alphaA-crystallin expression in the lens, but not
      in retina, spleen and thymus. In addition, while the 15 kb Cryaa/EGFP region also
      supported the expression of EGFP in the lens pit, expression in regions such as
      the hindbrain, indicate that additional genomic regions may play modulatory
      functions in regulating extralenticular alphaA-crystallin expression. Finally,
      deletion of DCR3 in either alphaA-BAC(DeltaDCR3) or Cryaa (15 kb) transgenic mice
      result in EGFP expression patterns that are consistent with DCR's previously
      established role as a distal enhancer active in "late" primary lens fiber cells.

PMID- 18803848
TI  - Mutation screening of CHD5 in melanoma-prone families linked to 1p36 revealed no
      deleterious coding or splice site changes.
AB  - BACKGROUND: A subset of cutaneous malignant melanoma and dysplastic nevi (CMM/DN)
      families is linked to 1p36. To date, no CMM/DN susceptibility gene has been
      identified at this locus. Data from mouse studies identified chromodomain
      helicase DNA binding protein 5 (CHD5) as a tumor suppressor affecting cellular
      proliferation and apoptosis via the CDKN2A/p53 pathway. Based on these findings,
      we felt it was important to screen CHD5 as a familial CMM/DN susceptibility gene.
      METHODS: Eight unrelated CMM/DN families showing prior evidence of linkage to the
      1p36 locus were identified for CHD5 mutation screening. One CMM/DN affected and
      one unaffected individual from each family were selected for sequencing of the
      CHD5 coding exons and their respective intron-exon boundaries. CHD5 variants that
      were identified solely among affecteds in the screening panel were further
      assessed by sequencing additional affected and unaffected members of these
      families to determine if the variant co-segregated with the CMM/DN phenotype.
      RESULTS: Single nucleotide polymorphisms in the CHD5 intronic and coding regions
      were identified among affecteds in the screening panel. None of these variants
      completely co-segregated with CMM/DN affection status among these eight families.
      CONCLUSION: There is no evidence to support CHD5 as a major melanoma
      susceptibility gene among the eight CMM/DN families screened.

PMID- 18803849
TI  - A phase I/II trial of beta-(1,3)/(1,6) D-glucan in the treatment of patients with
      advanced malignancies receiving chemotherapy.
AB  - Beta-(1,3)/(1,6) D-glucan, a component of the fungal cell wall, has been shown to
      stimulate the immune system, enhance hematopoiesis, amplify killing of opsonized
      tumor cells and increase neutrophil chemotaxis and adhesion. In view of these
      attributes, the beta-glucans should be studied for both their therapeutic
      efficacy in patients with cancer as well as an adjunctive therapy in patients
      receiving chemotherapy as a maneuver to limit suppression of hematopoiesis.In
      this study, twenty patients with advanced malignancies receiving chemotherapy
      were given a beta-(1,3)/(1,6) D-glucan preparation (MacroForce plus IP6,
      ImmuDyne, Inc.) and monitored for tolerability and effect on hematopoiesis. Our
      results lead us to conclude that beta-glucan is well-tolerated in cancer patients
      receiving chemotherapy, may have a beneficial effect on hematopoiesis in these
      patients and should be studied further, especially in patients with chronic
      lymphocytic leukemia and lymphoma.

PMID- 18803850
TI  - Menopausal hormone therapy in relation to breast cancer characteristics and
      prognosis: a cohort study.
AB  - INTRODUCTION: Menopausal hormone therapy has been reported to increase the risk
      of certain subtypes of breast cancer and to be associated with a favorable
      survival. These associations could either be due to an increased mammographic
      surveillance or to a biological effect. We assessed these associations in a
      Swedish cohort of postmenopausal breast cancer patients holding information on
      mammographic examinations, menopausal hormone therapy use, other breast cancer
      risk factors, and cancer treatment. METHODS: We analyzed 2,660 postmenopausal
      women aged 50 to 74 years, diagnosed with invasive breast cancer in 1993 to 1995
      and followed until the end of 2003 (median follow-up, 9 years and 3 months). We
      assessed the influence of hormone therapy before diagnosis on tumor
      characteristics and breast cancer-specific survival. We analyzed hormone therapy
      before diagnosis by regimen (estrogen-progestin therapy or estrogen alone
      therapy), recency (current or past), and duration of use (<5 years or > or = 5
      years). RESULTS: Current use, but not past use, compared with never use of
      hormone therapy before diagnosis seemed to be associated with tumors of low grade
      and with improved breast cancer-specific survival. The associations were stronger
      with longer duration, but did not vary significantly by regimen. The favorable
      survival among current users of hormone therapy was only partly explained by
      differences in available tumor characteristics and mammographic surveillance.
      CONCLUSIONS: We conclude that current menopausal hormone therapy, especially long
      term, is associated with favorable tumor characteristics and survival.

PMID- 18803851
TI  - Aging and partial body weight support affects gait variability.
AB  - BACKGROUND: Aging leads to increases in gait variability which may explain the
      large incidence of falls in the elderly. Body weight support training may be
      utilized to improve gait in the elderly and minimize falls. However, before
      initiating rehabilitation protocols, baseline studies are needed to identify the
      effect of body weight support on elderly gait variability. Our purpose was to
      determine the kinematic variability of the lower extremities in young and elderly
      healthy females at changing levels of body weight support during walking.
      METHODS: Ten young and ten elderly females walked on a treadmill for two minutes
      with a body weight support (BWS) system under four different conditions: 1 g, 0.9
      g, 0.8 g, and 0.7 g. Three-dimensional kinematics was captured at 60 Hz with a
      Peak Performance high speed video system. Magnitude and structure of variability
      of the sagittal plane angular kinematics of the right lower extremity was
      analyzed using both linear (magnitude; standard deviations and coefficient of
      variations) and nonlinear (structure; Lyapunov exponents) measures. A two way
      mixed ANOVA was used to evaluate the effect of age and BWS on variability.
      RESULTS: Linear analysis showed that the elderly presented significantly more
      variability at the hip and knee joint than the young females. Moreover, higher
      levels of BWS presented increased variability at all joints as found in both the
      linear and nonlinear measures utilized. CONCLUSION: Increased levels of BWS
      increased lower extremity kinematic variability. If the intent of BWS training is
      to decrease variability in gait patterns, this did not occur based on our
      results. However, we did not perform a training study. Thus, it is possible that
      after several weeks of training and increased habituation, these initial
      increased variability values will decrease. This assumption needs to be addressed
      in future investigation with both "healthy" elderly and elderly fallers. In
      addition, it is possible that BWS training can have a positive transfer effect by
      bringing overground kinematic variability to healthy normative levels, which also
      needs to be explored in future studies.

PMID- 18803852
TI  - POEM, A 3-dimensional exon taxonomy and patterns in untranslated exons.
AB  - BACKGROUND: The existence of exons and introns has been known for thirty years.
      Despite this knowledge, there is a lack of formal research into the
      categorization of exons. Exon taxonomies used by researchers tend to be selected
      ad hoc or based on an information poor de-facto standard. Exons have been shown
      to have specific properties and functions based on among other things their
      location and order. These factors should play a role in the naming to increase
      specificity about which exon type(s) are in question. RESULTS: POEM (Protein
      Oriented Exon Monikers) is a new taxonomy focused on protein proximal exons. It
      integrates three dimensions of information (Global Position, Regional Position
      and Region), thus its exon categories are based on known statistical exon
      features. POEM is applied to two congruent untranslated exon datasets resulting
      in the following statistical properties. Using the POEM taxonomy previous wide
      ranging estimates of initial 5' untranslated region exons are resolved. According
      to our datasets, 29-36% of genes have wholly untranslated first exons.
      Untranslated exon containing sequences are shown to have consistently up to 6
      times more 5' untranslated exons than 3' untranslated exons. Finally, three exon
      patterns are determined which account for 70% of untranslated exon genes.
      CONCLUSION: We describe a thorough three-dimensional exon taxonomy called POEM,
      which is biologically and statistically relevant. No previous taxonomy provides
      such fine grained information and yet still includes all valid information
      dimensions. The use of POEM will improve the accuracy of genefinder comparisons
      and analysis by means of a common taxonomy. It will also facilitate unambiguous
      communication due to its fine granularity.

PMID- 18803853
TI  - "TOF2H": a precision toolbox for rapid, high density/high coverage hydrogen
      deuterium exchange mass spectrometry via an LC-MALDI approach, covering the data
      pipeline from spectral acquisition to HDX rate analysis.
AB  - BACKGROUND: Protein-amide proton hydrogen-deuterium exchange (HDX) is used to
      investigate protein conformation, conformational changes and surface binding
      sites for other molecules. To our knowledge, software tools to automate data
      processing and analysis from sample fractionating (LC-MALDI) mass-spectrometry
      based HDX workflows are not publicly available. RESULTS: An integrated data
      pipeline (Solvent Explorer/TOF2H) has been developed for the processing of LC
      MALDI-derived HDX data. Based on an experiment-wide template, and taking an ab
      initio approach to chromatographic and spectral peak finding, initial data
      processing is based on accurate mass-matching to fully deisotoped peaklists
      accommodating, in MS/MS-confirmed peptide library searches, ambiguous mass-hits
      to non-target proteins. Isotope-shift re-interrogation of library search results
      allows quick assessment of the extent of deuteration from peaklist data alone.
      During raw spectrum editing, each spectral segment is validated in real time,
      consistent with the manageable spectral numbers resulting from LC-MALDI
      experiments. A semi-automated spectral-segment editor includes a semi-automated
      or automated assessment of the quality of all spectral segments as they are
      pooled across an XIC peak for summing, centroid mass determination, building of
      rates plots on-the-fly, and automated back exchange correction. The resulting
      deuterium uptake rates plots from various experiments can be averaged,
      subtracted, re-scaled, error-barred, and/or scatter-plotted from individual
      spectral segment centroids, compared to solvent exposure and hydrogen bonding
      predictions and receive a color suggestion for 3D visualization. This software
      lends itself to a "divorced" HDX approach in which MS/MS-confirmed peptide
      libraries are built via nano or standard ESI without source modification, and HDX
      is performed via LC-MALDI using a standard MALDI-TOF. The complete TOF2H package
      includes additional (eg LC analysis) modules. CONCLUSION: "TOF2H" provides a
      comprehensive HDX data analysis package that has accelerated the processing of LC
      MALDI-based HDX data in the authors' lab from weeks to hours. It runs in a
      standard MS Windows (XP or Vista) environment, and can be downloaded
      http://tof2h.bio.uci.edu or obtained from the authors at no cost.

PMID- 18803854
TI  - Welcome to molecular brain.
AB  - We are delighted to announce the arrival of a brand new journal dedicated to the
      ever-expanding field of neuroscience. Molecular Brain is a peer-reviewed, open
      access online journal that aims at publishing high quality articles as rapidly as
      possible. The journal will cover a broad spectrum of neuroscience ranging from
      molecular/cellular to behavioral/cognitive neuroscience and from basic to
      clinical research. Molecular Brain will publish not only research articles, but
      also methodology articles, editorials, reviews, and short reports. It will be a
      premier platform for neuroscientists to exchange their ideas with researchers
      from around the world to help improve our understanding of the molecular
      mechanisms of the brain and mind.

PMID- 18803855
TI  - Transcriptional regulation of long-term memory in the marine snail Aplysia.
AB  - Whereas the induction of short-term memory involves only covalent modifications
      of constitutively expressed preexisting proteins, the formation of long-term
      memory requires gene expression, new RNA, and new protein synthesis. On the
      cellular level, transcriptional regulation is thought to be the starting point
      for a series of molecular steps necessary for both the initiation and maintenance
      of long-term synaptic facilitation (LTF). The core molecular features of
      transcriptional regulation involved in the long-term process are evolutionally
      conserved in Aplysia, Drosophila, and mouse, and indicate that gene regulation by
      the cyclic AMP response element binding protein (CREB) acting in conjunction with
      different combinations of transcriptional factors is critical for the expression
      of many forms of long-term memory. In the marine snail Aplysia, the molecular
      mechanisms that underlie the storage of long-term memory have been extensively
      studied in the monosynaptic connections between identified sensory neuron and
      motor neurons of the gill-withdrawal reflex. One tail shock or one pulse of
      serotonin (5-HT), a modulatory transmitter released by tail shocks, produces a
      transient facilitation mediated by the cAMP-dependent protein kinase leading to
      covalent modifications in the sensory neurons that results in an enhancement of
      transmitter release and a strengthening of synaptic connections lasting minutes.
      By contrast, repeated pulses of 5-hydroxytryptamine (5-HT) induce a transcription
      and translation-dependent long-term facilitation (LTF) lasting more than 24 h
      and trigger the activation of a family of transcription factors in the
      presynaptic sensory neurons including ApCREB1, ApCREB2 and ApC/EBP. In addition,
      we have recently identified novel transcription factors that modulate the
      expression of ApC/EBP and also are critically involved in LTF. In this review, we
      examine the roles of these transcription factors during consolidation of LTF
      induced by different stimulation paradigms.

PMID- 18803856
TI  - Cingulate NMDA NR2B receptors contribute to morphine-induced analgesic tolerance.
AB  - Morphine is widely used to treat chronic pain, however its utility is hindered by
      the development of tolerance to its analgesic effects. While N-methyl-D-aspartate
      (NMDA) receptors are known to play roles in morphine tolerance and dependence,
      less is known about the roles of individual NMDA receptor subtypes. In this
      study, Ro 256981, an antagonist of the NMDA receptor subunit NR2B, was used to
      reduce the expression of analgesic tolerance to morphine. The mechanisms altered
      with chronic drug use share similarities with those underlying the establishment
      of long-tem potentiation (LTP) and behavioral memory. Since NMDA NR2B receptors
      in the anterior cingulate cortex (ACC) play roles in the establishment of LTP and
      fear memory, we explored their role in changes that occur in this region after
      chronic morphine. Both systemic and intra-ACC inhibition of NR2B in morphine
      tolerant animals inhibited the expression of analgesic tolerance.
      Electrophysiological recordings revealed a significant increase in the NR2B
      component of NMDA receptor mediated excitatory postsynaptic currents (EPSCs), at
      both synaptic and extra-synaptic sites. However, there was no change in alpha
      amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor mediated
      EPSCs. This study suggests that selective inhibition of NMDA NR2B receptors may
      prove useful in combating the development of analgesic tolerance to morphine and
      proposes a novel role for the ACC in opioid tolerance and morphine induced
      changes in synaptic plasticity.

PMID- 18803857
TI  - Atypical evening cortisol profile induces visual recognition memory deficit in
      healthy human subjects.
AB  - BACKGROUND: Diurnal rhythm-mediated endogenous cortisol levels in humans are
      characterised by a peak in secretion after awakening that declines throughout the
      day to an evening trough. However, a significant proportion of the population
      exhibits an atypical cycle of diurnal cortisol due to shift work, jet-lag, aging,
      and mental illness. RESULTS: The present study has demonstrated a correlation
      between elevation of cortisol in the evening and deterioration of visual object
      recognition memory. However, high evening cortisol levels have no effect on
      spatial memory. CONCLUSION: This study suggests that atypical evening salivary
      cortisol levels have an important role in the early deterioration of recognition
      memory. The loss of recognition memory, which is vital for everyday life, is a
      major symptom of the amnesic syndrome and early stages of Alzheimer's disease.
      Therefore, this study will promote a potential physiologic marker of early
      deterioration of recognition memory and a possible diagnostic strategy for
      Alzheimer's disease.

PMID- 18803858
TI  - Starting at the endophenotype: A role for alpha-CaMKII in schizophrenia?
AB  - Using an endophenotype-driven screen, a new study finds that alpha
      calcium/calmodulin kinase II mutant mice exhibit a range of behavioral
      abnormalities related to schizophrenia. Perhaps most strikingly, this cluster of
      schizophrenia-related endophenotypes was associated with abnormal neurogenesis in
      the adult hippocampus, raising the possibility that disrupted adult neurogenesis
      lies at the core of this and other psychiatric disorders.

PMID- 18803859
TI  - Transplanted astrocytes derived from BMP- or CNTF-treated glial-restricted
      precursors have opposite effects on recovery and allodynia after spinal cord
      injury.
AB  - BACKGROUND: Two critical challenges in developing cell-transplantation therapies
      for injured or diseased tissues are to identify optimal cells and harmful side
      effects. This is of particular concern in the case of spinal cord injury, where
      recent studies have shown that transplanted neuroepithelial stem cells can
      generate pain syndromes. RESULTS: We have previously shown that astrocytes
      derived from glial-restricted precursor cells (GRPs) treated with bone
      morphogenetic protein-4 (BMP-4) can promote robust axon regeneration and
      functional recovery when transplanted into rat spinal cord injuries. In contrast,
      we now show that transplantation of GRP-derived astrocytes (GDAs) generated by
      exposure to the gp130 agonist ciliary neurotrophic factor (GDAs(CNTF)), the other
      major signaling pathway involved in astrogenesis, results in failure of axon
      regeneration and functional recovery. Moreover, transplantation of GDA(CNTF)
      cells promoted the onset of mechanical allodynia and thermal hyperalgesia at 2
      weeks after injury, an effect that persisted through 5 weeks post-injury. Delayed
      onset of similar neuropathic pain was also caused by transplantation of
      undifferentiated GRPs. In contrast, rats transplanted with GDAs(BMP) did not
      exhibit pain syndromes. CONCLUSION: Our results show that not all astrocytes
      derived from embryonic precursors are equally beneficial for spinal cord repair
      and they provide the first identification of a differentiated neural cell type
      that can cause pain syndromes on transplantation into the damaged spinal cord,
      emphasizing the importance of evaluating the capacity of candidate cells to cause
      allodynia before initiating clinical trials. They also confirm the particular
      promise of GDAs treated with bone morphogenetic protein for spinal cord injury
      repair.

PMID- 18803860
TI  - An analysis of hospital preparedness capacity for public health emergency in four
      regions of China: Beijing, Shandong, Guangxi, and Hainan.
AB  - BACKGROUND: Hospital preparedness is critical for the early detection and
      management of public health emergency (PHE). Understanding the current status of
      PHE preparedness is the first step in planning to enhance hospitals' capacities
      for emergency response. The objective of this study is to understand the current
      status of hospital PHE preparedness in China. METHODS: Four hundred hospitals in
      four city and provinces of China were surveyed using a standardized
      questionnaire. Data related to hospital demographic data; PHE preparation;
      response to PHE in community; stockpiles of drugs and materials; detection and
      identification of PHE; procedures for medical treatment; laboratory diagnosis and
      management; staff training; and risk communication were collected and analyzed.
      RESULTS: Valid responses were received from 318 (79.5%) of the 400 hospitals
      surveyed. Of the valid responses, 264 (85.2%) hospitals had emergency plans;
      93.3% had command centres and personnel for PHE; 22.9% included community
      organisations during the training for PHE; 97.4% could transport needed medical
      staff to a PHE; 53.1% had evaluated stockpiles of drugs; 61.5% had evaluated
      their supply systems; 55.5% had developed surveillance systems; and 74.6% could
      monitor the abnormity(See in appendix). Physicians in 80.2% of the analyzed
      hospitals reported up-to-date knowledge of their institution's PHE protocol. Of
      the 318 respondents, 97.4% followed strict laboratory regulations, however, only
      about 33.5% had protocols for suspected samples. Furthermore, only 59.0% could
      isolate and identify salmonella and staphylococcus and less than 5% could isolate
      and identify human H5N1 avian flu and SARS. Staff training or drill programs were
      reported in 94.5% of the institutions; 50.3% periodically assessed the efficacy
      of staff training; 45% had experts to provide psychological counselling; 12.1%
      had provided training for their medical staff to assess PHE-related stress. All
      of the above capacities related to the demographic characteristics of hospitals
      and will be discussed in-depth in this paper. CONCLUSION: Our survey suggested
      that, at the time of the survey, hospital preparedness for PHE in China was at an
      early stage of development. Comprehensive measures should be taken to enhance
      hospital capacity in the prevention and management of PHE.

PMID- 18803861
TI  - Anterolateral papillary muscle rupture caused by myocardial infarction: A case
      report.
AB  - BACKGROUND: The rupture of the anterolateral papillary muscle is less common than
      the posteromedial papillary muscle since the anterolateral muscle has dual blood
      supplies, while the posteromedial papillary muscle has a single blood supply.
      CASE PRESENTATION: We present a case report of a 42 year old male presenting with
      heart failure being diagnosed to have mitral regurgitation from the partial
      rupture of the anterolateral papillary muscle due to coronary artery disease. The
      patient underwent a mitral valve replacement and concomitant coronary artery
      bypass grafting of the first and the second obtuse marginal arteries. CONCLUSION:
      Acute mitral regurgitation can be precipitated by acute myocardial infarction due
      to rupture of the anterolateral papillary muscle.

PMID- 18803862
TI  - A pilot study of rivastigmine in the treatment of delirium after stroke: a safe
      alternative.
AB  - BACKGROUND: Delirium is a common disorder in the early phase of stroke. Given the
      presumed cholinergic deficiency in delirium, we tested treatment with the
      acetylcholinesterase inhibitor rivastigmine. METHODS: This pilot study was
      performed within an epidemiological study. In 527 consecutive stroke patients
      presence of delirium was assessed during the first week with the confusion
      assessment method. Severity was scored with the delirium rating scale (DRS).
      Sixty-two patients developed a delirium in the acute phase of stroke. Only
      patients with a severe and persistent delirium (defined as a DRS of 12 or more
      for more than 24 hours) were enrolled in the present study. In total 26 fulfilled
      these criteria of whom 17 were treated with orally administered rivastigmine with
      a total dose between 3 and 12 mg a day. Eight patients could not be treated
      because of dysphagia and one because of early discharge. RESULTS: No major side
      effects were recorded. In 16 patients there was a considerable decrease in
      severity of delirium. The mean DRS declined from 14.8 on day one to 8.5 after
      therapy and 5.6 after tapering. The mean duration of delirium was 6.7 days
      (range; 2-17). CONCLUSION: Rivastigmine is safe in stroke patients with delirium
      even after rapid titration. In the majority of patients the delirium improved
      after treatment. A randomized controlled trial is needed to establish the
      usefulness of rivastigmine in delirium after stroke. TRIAL REGISTRATION:
      Nederlands Trial Register NTR1395.

PMID- 18803863
TI  - Analysis of the goldfish Carassius auratus olfactory epithelium transcriptome
      reveals the presence of numerous non-olfactory GPCR and putative receptors for
      progestin pheromones.
AB  - BACKGROUND: The goldfish (Carassius auratus) uses steroids and prostaglandins as
      pheromone cues at different stages of the reproductive cycle to facilitate
      spawning synchronization. Steroid progestin pheromone binding has been detected
      in goldfish olfactory membranes but the receptors responsible for this specific
      binding remain unknown. In order to shed some light on the olfactory epithelium
      transcriptome and search for possible receptor candidates a large set of EST from
      this tissue were analysed and compared to and combined with a similar zebrafish
      (Danio rerio) resource. RESULTS: We generated 4,797 high quality sequences from a
      normalized cDNA library of the goldfish olfactory epithelium, which were
      clustered in 3,879 unique sequences, grouped in 668 contigs and 3,211 singletons.
      BLASTX searches produced 3,243 significant (E-value < e(-10)) hits and Gene
      Ontology (GO) analysis annotated a further 1,223 of these genes (37.7%).
      Comparative analysis with zebrafish olfactory epithelium ESTs revealed 1,088
      identical unigenes. The transcriptome size of both species was estimated at about
      16,400 unigenes, based on the proportion of genes identified involved in Glucose
      Metabolic Process. Of 124 G-protein coupled receptors identified in the olfactory
      epithelium of both species, 56 were olfactory receptors. Beta and gamma membrane
      progestin receptors were also isolated by subcloning of RT-PCR products from both
      species and an olfactory epithelium specific splice form identified. CONCLUSION:
      The high similarity between the goldfish and zebrafish olfactory systems allowed
      the creation of a 'cyprinid' olfactory epithelium library estimated to represent
      circa 70% of the transcriptome. These results are an important resource for the
      identification of components of signalling pathways involved in olfaction as well
      as putative targets for pharmacological and histochemical studies. The possible
      function of the receptors identified in the olfactory system is described.
      Moreover, the role of olfactory epithelium specific isoforms of classical
      membrane progestin receptor genes as candidates for preovulatory pheromone
      sensing is discussed.

PMID- 18803864
TI  - Over a millon Creatine Kinase due to a heavy work-out: A case report.
AB  - Rhabdomyolysis induced by exercise is a very well known entity, several cases
      has been reported in the literature related with strenuous activities, weight
      lifting, marathon running, overexertion in an untrained person, knee bends, etc.
      We reported an interesting case of exercise-induced rhabdomyolysis in a 25 year
      old Hispanic male, after resuming his regular physical activity, with the highest
      creatine kinase described in the literature, successfully treated with aggressive
      hydration only and no complications.

PMID- 18803865
TI  - Antibacterial and antioxidant properties of the methanol extracts of the leaves
      and stems of Calpurnia aurea.
AB  - BACKGROUND: In South Africa, Calpurnia aurea (Ait.) Benth is used to destroy lice
      and to relieve itches, to destroy maggots and to treat allergic rashes,
      particularly those caused by caterpillars. Antioxidants play an important role
      protecting against damage by reactive oxygen species. Plants containing
      flavonoids have been reported to possess strong antioxidant properties. METHODS:
      The antibacterial, antioxidant activities and phenolic contents of the methanol
      extracts of the leaves and stems of Calpurnia aurea were evaluated using in vitro
      standard methods. Spectrophotometry was the basis for the determinations of total
      phenol, total flavonoids, flavonols, and proanthocyanidins. Tannins, quercetin
      and catechin equivalents were used for these parameters. The antioxidant
      activities of the stem extract of Calpurnia aurea were determined by ABTS, DPPH,
      and ferrous reducing antioxidant property (FRAP) methods. Laboratory isolates of
      10 bacteria species which included five Gram-positive and five Gram-negative
      strains were used to assay for antibacterial activity of this plant. RESULTS: The
      results from this study showed that the antioxidant activities of the stem
      extract of Calpurnia aurea as determined by the total phenol, flavonoids, and
      FRAP methods were higher than that of the leaves. On the other hand, the leaf
      extract of the plant has higher level of total flavonols and proanthocyanidins.
      The leaf extract also has higher radical scavenging activity as shown in 1, 1
      Diphenyl-2-picrylhydrazyl (DPPH), and 2,2?-azinobis-3- ethylbenzothiazoline-6
      sulfonic acid (ABTS) assay. The leaf extract showed activity against seven of the
      bacterial organisms. CONCLUSION: The results from this study indicate that the
      leaves and stem extracts of Calpurnia aurea possess antioxidant properties and
      could serve as free radical inhibitors or scavenger or, acting possibly as
      primary antioxidants. Although, the antibacterial properties of Calpurnia aurea
      are not as effective as the standard drugs- Chloramphenicol and Streptomycin,
      they still possess some activity against bacterial strains used in this study.
      Calpurnia aurea may therefore be a good candidate for functional foods as well as
      pharmaceutical plant-based products.

PMID- 18803866
TI  - The effect of long-term homocysteine-lowering on carotid intima-media thickness
      and flow-mediated vasodilation in stroke patients: a randomized controlled trial
      and meta-analysis.
AB  - BACKGROUND: Experimental and epidemiological evidence suggests that homocysteine
      (tHcy) may be a causal risk factor for atherosclerosis. B-vitamin supplements
      reduce tHcy and improve endothelial function in short term trials, but the long
      term effects of the treatment on vascular structure and function are unknown.
      METHODS: We conducted a sub-study of VITATOPS, a randomised, double-blind,
      placebo-controlled intervention trial designed to test the efficacy of long term
      B-vitamin supplementation (folic acid 2 mg, vitamin B6 25 mg and vitamin B12 0.5
      mg) in the prevention of vascular events in patients with a history of stroke. We
      measured carotid intima-medial thickness (CIMT) and flow-mediated dilation (FMD)
      at least two years after randomisation in 162 VITATOPS participants. We also
      conducted a systematic review and meta-analysis of studies designed to test the
      effect of B-vitamin treatment on CIMT and FMD. RESULTS: After a mean treatment
      period of 3.9 +/- 0.9 years, the vitamin-treated group had a significantly lower
      mean plasma homocysteine concentration than the placebo-treated group (7.9
      micromol/L, 95% CI 7.5 to 8.4 versus 11.8 micromol/L, 95% CI 10.9 to 12.8, p <
      0.001). Post-treatment CIMT (0.84 +/- 0.17 mm vitamins versus 0.83 +/- 0.18 mm
      placebo, p = 0.74) and FMD (median of 4.0%, IQR 0.9 to 7.2 vitamins versus 3.0%,
      IQR 0.6 to 6.6 placebo, p = 0.48) did not differ significantly between groups. A
      meta-analysis of published randomised data, including those from the current
      study, suggested that B-vitamin supplements should reduce CIMT (-0.10 mm, 95% CI 
      0.20 to -0.01 mm) and increase FMD (1.4%, 95% CI 0.7 to 2.1%). However, the
      improvement in endothelial function associated with homocysteine-lowering
      treatment was significant in short-term studies but not in longer trials.
      CONCLUSION: Although short-term treatment with B-vitamins is associated with
      increased FMD, long-term homocysteine-lowering did not significantly improve FMD
      or CIMT in people with a history of stroke.

PMID- 18803867
TI  - Sequence based residue depth prediction using evolutionary information and
      predicted secondary structure.
AB  - BACKGROUND: Residue depth allows determining how deeply a given residue is
      buried, in contrast to the solvent accessibility that differentiates between
      buried and solvent-exposed residues. When compared with the solvent
      accessibility, the depth allows studying deep-level structures and functional
      sites, and formation of the protein folding nucleus. Accurate prediction of
      residue depth would provide valuable information for fold recognition, prediction
      of functional sites, and protein design. RESULTS: A new method, RDPred, for the
      real-value depth prediction from protein sequence is proposed. RDPred combines
      information extracted from the sequence, PSI-BLAST scoring matrices, and
      secondary structure predicted with PSIPRED. Three-fold/ten-fold cross validation
      based tests performed on three independent, low-identity datasets show that the
      distance based depth (computed using MSMS) predicted by RDPred is characterized
      by 0.67/0.67, 0.66/0.67, and 0.64/0.65 correlation with the actual depth, by the
      mean absolute errors equal 0.56/0.56, 0.61/0.60, and 0.58/0.57, and by the mean
      relative errors equal 17.0%/16.9%, 18.2%/18.1%, and 17.7%/17.6%, respectively.
      The mean absolute and the mean relative errors are shown to be statistically
      significantly better when compared with a method recently proposed by Yuan and
      Wang [Proteins 2008; 70:509-516]. The results show that three-fold cross
      validation underestimates the variability of the prediction quality when compared
      with the results based on the ten-fold cross validation. We also show that the
      hydrophilic and flexible residues are predicted more accurately than hydrophobic
      and rigid residues. Similarly, the charged residues that include Lys, Glu, Asp,
      and Arg are the most accurately predicted. Our analysis reveals that evolutionary
      information encoded using PSSM is characterized by stronger correlation with the
      depth for hydrophilic amino acids (AAs) and aliphatic AAs when compared with
      hydrophobic AAs and aromatic AAs. Finally, we show that the secondary structure
      of coils and strands is useful in depth prediction, in contrast to helices that
      have relatively uniform distribution over the protein depth. Application of the
      predicted residue depth to prediction of buried/exposed residues shows consistent
      improvements in detection rates of both buried and exposed residues when compared
      with the competing method. Finally, we contrasted the prediction performance
      among distance based (MSMS and DPX) and volume based (SADIC) depth definitions.
      We found that the distance based indices are harder to predict due to the more
      complex nature of the corresponding depth profiles. CONCLUSION: The proposed
      method, RDPred, provides statistically significantly better predictions of
      residue depth when compared with the competing method. The predicted depth can be
      used to provide improved prediction of both buried and exposed residues. The
      prediction of exposed residues has implications in characterization/prediction of
      interactions with ligands and other proteins, while the prediction of buried
      residues could be used in the context of folding predictions and simulations.

PMID- 18803868
TI  - Lack of genomic evidence of AI-2 receptors suggests a non-quorum sensing role for
      luxS in most bacteria.
AB  - BACKGROUND: Great excitement accompanied discoveries over the last decade in
      several Gram-negative and Gram-positive bacteria of the LuxS protein, which
      catalyzes production of the AI-2 autoinducer molecule for a second quorum sensing
      system (QS-2). Since the luxS gene was found to be widespread among the most
      diverse bacterial taxa, it was hypothesized that AI-2 may constitute the basis of
      a universal microbial language, a kind of bacterial Esperanto. Many of the
      studies published in this field have drawn a direct correlation between the
      occurrence of the luxS gene in a given organism and the presence and
      functionality of a QS-2 therein. However, rarely hathe existence of potential AI
      2 receptors been examined. This is important, since it is now well recognized
      that LuxS also holds a central role as a metabolic enzyme in the activated methyl
      cycle which is responsible for the generation of S-adenosyl-L-methionine, the
      major methyl donor in the cell. RESULTS: In order to assess whether the role of
      LuxS in these bacteria is indeed related to AI-2 mediated quorum sensing we
      analyzed genomic databases searching for established AI-2 receptors (i.e., LuxPQ
      receptor of Vibrio harveyi and Lsr ABC-transporter of Salmonella typhimurium) and
      other presumed QS-related proteins and compared the outcome with published
      results about the role of QS-2 in these organisms. An unequivocal AI-2 related
      behavior was restricted primarily to organisms bearing known AI-2 receptor genes,
      while phenotypes of luxS mutant bacteria lacking these genes could often be
      explained simply by assuming deficiencies in sulfur metabolism. CONCLUSION:
      Genomic analysis shows that while LuxPQ is restricted to Vibrionales, the Lsr
      receptor complex is mainly present in pathogenic bacteria associated with
      endotherms. This suggests that QS-2 may play an important role in interactions
      with animal hosts. In most other species, however, the role of LuxS appears to be
      limited to metabolism, although in a few cases the presence of yet unknown
      receptors or the adaptation of pre-existent effectors to QS-2 must be postulated.

PMID- 18803869
TI  - The information highways of a biotechnological workhorse--signal transduction in
      Hypocrea jecorina.
AB  - BACKGROUND: The ascomycete Hypocrea jecorina (anamorph Trichoderma reesei) is one
      of the most prolific producers of biomass-degrading enzymes and frequently termed
      an industrial workhorse. To compete for nutrients in its habitat despite its
      shortcoming in certain degradative enzymes, efficient perception and
      interpretation of environmental signals is indispensable. A better understanding
      of these signals as well as their transmission machinery can provide sources for
      improvement of biotechnological processes. RESULTS: The genome of H. jecorina was
      analysed for the presence and composition of common signal transduction pathways
      including heterotrimeric G-protein cascades, cAMP signaling, mitogen activated
      protein kinases, two component phosphorelay systems, proteins involved in
      circadian rhythmicity and light response, calcium signaling and the superfamily
      of Ras small GTPases. The results of this survey are discussed in the context of
      current knowledge in order to assess putative functions as well as potential
      impact of alterations of the respective pathways. CONCLUSION: Important findings
      include an additional, bacterial type phospholipase C protein and an additional 6
      4 photolyase. Moreover the presence of 4 RGS-(Regulator of G-protein Signaling)
      proteins and 3 GprK-type G-protein coupled receptors comprising an RGS-domain
      suggest a more complex posttranslational regulation of G-protein signaling than
      in other ascomycetes. Also the finding, that H. jecorina, unlike yeast possesses
      class I phosducins which are involved in phototransduction in mammals warrants
      further investigation. An alteration in the regulation of circadian rhythmicity
      may be deduced from the extension of both the class I and II of casein kinases,
      homologues of which are implicated in phosphorylation of FRQ in Neurospora
      crassa. On the other hand, a shortage in the number of the pathogenicity related
      PTH11-type G-protein coupled receptors (GPCRs) as well as a lack of microbial
      opsins was detected. Considering its efficient enzyme system for breakdown of
      cellulosic materials, it came as a surprise that H. jecorina does not possess a
      carbon sensing GPCR.

PMID- 18803870
TI  - Identification of symptom domains in ulcerative colitis that occur frequently
      during flares and are responsive to changes in disease activity.
AB  - BACKGROUND: Ulcerative colitis disease activity is determined by measuring
      symptoms and signs. Our aim was to determine which symptom domains are frequent
      and responsive to change in the evaluation of disease activity, which are those
      defined by three criteria: 1) they occur frequently during flares; 2) they
      improve during effective therapy for ulcerative colitis; and 3) they resolve
      during remission. METHODS: Twenty-eight symptom domains, 16 from standard indices
      and 12 novel domains identified by ulcerative colitis patient focus groups, were
      evaluated. Sixty subjects with ulcerative colitis were surveyed, rating each
      symptom on the three criteria with a 100 mm Visual Analogue Scale. Frequent and
      responsive symptoms were defined a priori as those whose median Visual Analogue
      Scale rating for all 3 criteria was significantly greater than 50. RESULTS:
      Thirteen of the 28 symptom domains were identified as both frequent in ulcerative
      colitis flares and responsive to changes in disease activity. Seven of these 13
      symptom domains were novel symptoms derived from ulcerative colitis patient focus
      groups including stool mucus, tenesmus, fatigue, rapid postprandial bowel
      movements, and inability to differentiate liquid or gas from solid stool when
      rectal urgency occurs. Ten of the 16 symptom domains from standard indices were
      either infrequent or unresponsive to changes in disease activity. CONCLUSION:
      Only some of the symptoms of ulcerative colitis that are important to patients
      are included in standard indices, and several symptoms currently measured are not
      frequent or responsive to change in ulcerative colitis patients. Development of
      survey measures of these symptom domains could significantly improve the
      assessment of disease activity in ulcerative colitis.

PMID- 18803871
TI  - How does age affect baseline screening mammography performance measures? A
      decision model.
AB  - BACKGROUND: In order to promote consumer-oriented informed medical decision
      making regarding screening mammography, we created a decision model to predict
      the age dependence of the cancer detection rate, the recall rate and the
      secondary performance measures (positive predictive values, total intervention
      rate, and positive biopsy fraction) for a baseline mammogram. METHODS: We
      constructed a decision tree to model the possible outcomes of a baseline
      screening mammogram in women ages 35 to 65. We compared the single baseline
      screening mammogram decision with the no screening alternative. We used the
      Surveillance Epidemiology and End Results national cancer database as the primary
      input to estimate cancer prevalence. For other probabilities, the model used
      population-based estimates for screening mammography accuracy and diagnostic
      mammography outcomes specific to baseline exams. We varied radiologist
      performance for screening accuracy. RESULTS: The cancer detection rate increases
      from 1.9/1000 at age 40 to 7.2/1000 at age 50 to 15.1/1000 at age 60. The recall
      rate remains relatively stable at 142-157/1000, which varies from 73-236/1000 at
      age 50 depending on radiologist performance. The positive predictive value of a
      screening mammogram increases from 1.3% at age 40 to 9.8% at age 60, while the
      positive predictive value of a diagnostic mammogram varies from 2.9% at age 40 to
      19.2% at age 60. The model predicts the total intervention rate = 0.013*AGE2 -
      0.67*AGE + 40, or 34/1000 at age 40 to 47/1000 at age 60. Therefore, the positive
      biopsy (intervention) fraction varies from 6% at age 40 to 32% at age 60.
      CONCLUSION: Breast cancer prevalence, the cancer detection rate, and all
      secondary screening mammography performance measures increase substantially with
      age.

PMID- 18803872
TI  - Hfq regulates the expression of the thermostable direct hemolysin gene in Vibrio
      parahaemolyticus.
AB  - BACKGROUND: The hfq gene is conserved in a wide variety of bacteria and Hfq is
      involved in many cellular functions such as stress responses and the regulation
      of gene expression. It has also been reported that Hfq is involved in bacterial
      pathogenicity. However, it is not clear whether Hfq regulates virulence in Vibrio
      parahaemolyticus. To evaluate this, we investigated the effect of Hfq on the
      expression of virulence-associated genes including thermostable direct hemolysin
      (TDH), which is considered to be an important virulence factor in V.
      parahaemolyticus, using an hfq deletion mutant. RESULTS: The production of TDH in
      the hfq deletion mutant was much higher than in the parental strain.
      Quantification of tdh promoter activity and mRNA demonstrated that transcription
      of the tdh gene was up-regulated in the mutant strain. The hfq-complemented
      strain had a normal (parental) amount of tdh expression. The transcriptional
      activity of tdhA was particularly increased in the mutant strain. These results
      indicate that Hfq is closely associated with the expression level of the tdh
      gene. Interestingly, other genes involved in the pathogenicity of V.
      parahaemolyticus, such as VP1680, vopC, and vopT, were also up-regulated in the
      mutant strain. CONCLUSION: Hfq regulates the expression of virulence-associated
      factors such as TDH and may be involved in the pathogenicity of V.
      parahaemolyticus.

PMID- 18803873
TI  - Secular changes in height, weight and body mass index in Hong Kong Children.
AB  - BACKGROUND: Large population growth surveys of children and adolescents aged 6 to
      18 y were undertaken in Hong Kong in 1963 and 1993. The global epidemic of
      obesity is a major public health concern. To monitor the impact of this epidemic
      in Hong Kong children and to identify secular changes in growth, a further growth
      survey was undertaken in 2005/6. METHODS: Cross-sectional height and weight
      measurements of 14,842 children and adolescents aged 6 to 18 y from Hong Kong's
      18 districts were obtained during the 2005/6 school year. Percentile curves were
      constructed using LMS method and sex-specific percentile values of weight-for
      age, height-for-age, and BMI-for-age were compared with those data from 1963 and
      1993. RESULTS: Secular changes in height, weight and BMI were noted between 1963
      and 1993 and between 1993 and 2005/6. In the latter period, greater changes were
      observed at younger ages, and particularly in boys. On an annual basis, the 1993
      2005/6 changes were less than those during 1963-1993. Using the International
      Obesity Task Force cut-offs, 16.7% of children were overweight or obese in
      2005/6, which was a 5.1% increase since 1993. CONCLUSION: These data provide
      policy-makers with further evidence of the secular changes in child growth and
      the increasing obesity epidemic among Hong Kong children.

PMID- 18803874
TI  - Post tracheostomy and post intubation tracheal stenosis: report of 31 cases and
      review of the literature.
AB  - BACKGROUND: Severe post tracheostomy (PT) and post intubation (PI) tracheal
      stenosis is an uncommon clinical entity that often requires interventional
      bronchoscopy before surgery is considered. We present our experience with severe
      PI and PT stenosis in regards to patient characteristics, possible risk factors,
      and therapy. METHODS: We conducted a retrospective chart review of 31 patients
      with PI and PT stenosis treated at Lahey Clinic over the past 8 years.
      Demographic characteristics, body mass index, co-morbidities, stenosis type and
      site, procedures performed and local treatments applied were recorded. RESULTS:
      The most common profile of a patient with tracheal stenosis in our series was a
      female (75%), obese (66%) patient with a history of diabetes mellitus (35.4%),
      hypertension (51.6%), and cardiovascular disease (45.1%), who was a current
      smoker (38.7%). Eleven patients (PI group) had only oro-tracheal intubation (5.2
      days of intubation) and developed web-like stenosis at the cuff site. Twenty
      patients (PT group) had undergone tracheostomy (54.5 days of intubation) and in
      17 (85%) of them the stenosis appeared around the tracheal stoma. There was an
      average of 2.4 procedures performed per patient. Rigid bronchoscopy with Nd:YAG
      laser and dilatation (mechanical or balloon) were the preferred methods used.
      Only 1(3.2%) patient was sent to surgery for re-stenosis after multiple
      interventional bronchoscopy treatments. CONCLUSION: We have identified putative
      risk factors for the development of PI and PT stenosis. Differences in lesions
      characteristics and stenosis site were noted in our two patient groups. All
      patients underwent interventional bronchoscopy procedures as the first-line, and
      frequently the only treatment approach.

PMID- 18803875
TI  - Non-compliance with a postmastectomy radiotherapy guideline: decision tree and
      cause analysis.
AB  - BACKGROUND: The guideline for postmastectomy radiotherapy (PMRT), which is
      prescribed to reduce recurrence of breast cancer in the chest wall and improve
      overall survival, is not always followed. Identifying and extracting important
      patterns of non-compliance are crucial in maintaining the quality of care in
      Oncology. METHODS: Analysis of 759 patients with malignant breast cancer using
      decision tree induction (DTI) found patterns of non-compliance with the
      guideline. The PMRT guideline was used to separate cases according to the
      recommendation to receive or not receive PMRT. The two groups of patients were
      analyzed separately. Resulting patterns were transformed into rules that were
      then compared with the reasons that were extracted by manual inspection of
      records for the non-compliant cases. RESULTS: Analyzing patients in the group who
      should receive PMRT according to the guideline did not result in a robust
      decision tree. However, classification of the other group, patients who should
      not receive PMRT treatment according to the guideline, resulted in a tree with
      nine leaves and three of them were representing non-compliance with the
      guideline. In a comparison between rules resulting from these three non-compliant
      patterns and manual inspection of patient records, the following was found: In
      the decision tree, presence of perigland growth is the most important variable
      followed by number of malignantly invaded lymph nodes and level of Progesterone
      receptor. DNA index, age, size of the tumor and level of Estrogen receptor are
      also involved but with less importance. From manual inspection of the cases, the
      most frequent pattern for non-compliance is age above the threshold followed by
      near cut-off values for risk factors and unknown reasons. CONCLUSION: Comparison
      of patterns of non-compliance acquired from data mining and manual inspection of
      patient records demonstrates that not all of the non-compliances are repetitive
      or important. There are some overlaps between important variables acquired from
      manual inspection of patient records and data mining but they are not identical.
      Data mining can highlight non-compliance patterns valuable for guideline authors
      and for medical audit. Improving guidelines by using feedback from data mining
      can improve the quality of care in oncology.

PMID- 18803876
TI  - Development of a real-time multiplex PCR assay for the detection of multiple
      Salmonella serotypes in chicken samples.
AB  - BACKGROUND: A real-time multiplex PCR assay was developed for the detection of
      multiple Salmonella serotypes in chicken samples. Poultry-associated serotypes
      detected in the assay include Enteritidis, Gallinarum, Typhimurium, Kentucky and
      Dublin. The traditional cultural method according to EN ISO 6579:2002 for the
      detection of Salmonella in food was performed in parallel. The real-time PCR
      based method comprised a pre-enrichment step in Buffered Peptone Water (BPW)
      overnight, followed by a shortened selective enrichment in Rappaport Vasilliadis
      Soya Broth (RVS) for 6 hours and subsequent DNA extraction. RESULTS: The real
      time multiplex PCR assay and traditional cultural method showed 100% inclusivity
      and 100% exclusivity on all strains tested. The real-time multiplex PCR assay was
      as sensitive as the traditional cultural method in detecting Salmonella in
      artificially contaminated chicken samples and correctly identified the serotype.
      Artificially contaminated chicken samples resulted in a detection limit of
      between 1 and 10 CFU per 25 g sample for both methods. A total of sixty-three
      naturally contaminated chicken samples were investigated by both methods and
      relative accuracy, relative sensitivity and relative specificity of the real-time
      PCR method were determined to be 89, 94 and 87%, respectively. Thirty cultures
      blind tested were correctly identified by the real-time multiplex PCR method.
      CONCLUSION: Real-time PCR methodology can contribute to meet the need for rapid
      identification and detection methods in food testing laboratories.

PMID- 18803877
TI  - Retrospective study of adenovirus in autopsied pulmonary tissue of pediatric
      fatal pneumonia in South China.
AB  - BACKGROUND: Adenovirus are the important pathogen of pediatric severe pneumonia.
      The aim of this study is to analyze the infection, subtype and distribution of
      adenovirus in autopsied pulmonary tissue of fatal pneumonia in infants and
      children, and the relationships between adenovirus infection and respiratory
      illness in South China. METHODS: Nested PCR was performed on DNA extracted from
      autopsied lung tissue from patients who died of severe pneumonia, and the
      positive nested PCR products were cloned and sequenced. The adenovirus in
      autopsied pulmonary tissue was also analyzed by immunohistochemistry assay in a
      blind way. RESULTS: In the 175 autopsied pulmonary tissues, the positive
      percentage of adenovirus was 9.14% (16/175) and 2.29% (4/175) detected with
      nested PCR and immunohistochemistry, respectively. There are three cases of
      adenovirus serotype 3, twelve cases of adenovirus serotype 4 and one case of
      serotype 41 determined by sequencing of the cloned positive nested PCR products.
      CONCLUSION: Adenovirus is an important cause of severe pneumonia, and these data
      suggest that adenovirus serotype 4 might be an important pathogen responsible for
      the fatal pneumonia in Guangzhou, South China.

PMID- 18803878
TI  - The removal of multiplicative, systematic bias allows integration of breast
      cancer gene expression datasets - improving meta-analysis and prediction of
      prognosis.
AB  - BACKGROUND: The number of gene expression studies in the public domain is rapidly
      increasing, representing a highly valuable resource. However, dataset-specific
      bias precludes meta-analysis at the raw transcript level, even when the RNA is
      from comparable sources and has been processed on the same microarray platform
      using similar protocols. Here, we demonstrate, using Affymetrix data, that much
      of this bias can be removed, allowing multiple datasets to be legitimately
      combined for meaningful meta-analyses. RESULTS: A series of validation datasets
      comparing breast cancer and normal breast cell lines (MCF7 and MCF10A) were
      generated to examine the variability between datasets generated using different
      amounts of starting RNA, alternative protocols, different generations of
      Affymetrix GeneChip or scanning hardware. We demonstrate that systematic,
      multiplicative biases are introduced at the RNA, hybridization and image-capture
      stages of a microarray experiment. Simple batch mean-centering was found to
      significantly reduce the level of inter-experimental variation, allowing raw
      transcript levels to be compared across datasets with confidence. By accounting
      for dataset-specific bias, we were able to assemble the largest gene expression
      dataset of primary breast tumours to-date (1107), from six previously published
      studies. Using this meta-dataset, we demonstrate that combining greater numbers
      of datasets or tumours leads to a greater overlap in differentially expressed
      genes and more accurate prognostic predictions. However, this is highly dependent
      upon the composition of the datasets and patient characteristics. CONCLUSION:
      Multiplicative, systematic biases are introduced at many stages of microarray
      experiments. When these are reconciled, raw data can be directly integrated from
      different gene expression datasets leading to new biological findings with
      increased statistical power.

PMID- 18803879
TI  - Restoration of tumor suppressor miR-34 inhibits human p53-mutant gastric cancer
      tumorspheres.
AB  - BACKGROUND: MicroRNAs (miRNAs), some of which function as oncogenes or tumor
      suppressor genes, are involved in carcinogenesis via regulating cell
      proliferation and/or cell death. MicroRNA miR-34 was recently found to be a
      direct target of p53, functioning downstream of the p53 pathway as a tumor
      suppressor. miR-34 targets Notch, HMGA2, and Bcl-2, genes involved in the self
      renewal and survival of cancer stem cells. The role of miR-34 in gastric cancer
      has not been reported previously. In this study, we examined the effects of miR
      34 restoration on p53-mutant human gastric cancer cells and potential target gene
      expression. METHODS: Human gastric cancer cells were transfected with miR-34
      mimics or infected with the lentiviral miR-34-MIF expression system, and
      validated by miR-34 reporter assay using Bcl-2 3'UTR reporter. Potential target
      gene expression was assessed by Western blot for proteins, and by quantitative
      real-time RT-PCR for mRNAs. The effects of miR-34 restoration were assessed by
      cell growth assay, cell cycle analysis, caspase-3 activation, and cytotoxicity
      assay, as well as by tumorsphere formation and growth. RESULTS: Human gastric
      cancer Kato III cells with miR-34 restoration reduced the expression of target
      genes Bcl-2, Notch, and HMGA2. Bcl-2 3'UTR reporter assay showed that the
      transfected miR-34s were functional and confirmed that Bcl-2 is a direct target
      of miR-34. Restoration of miR-34 chemosensitized Kato III cells with a high level
      of Bcl-2, but not MKN-45 cells with a low level of Bcl-2. miR-34 impaired cell
      growth, accumulated the cells in G1 phase, increased caspase-3 activation, and,
      more significantly, inhibited tumorsphere formation and growth. CONCLUSION: Our
      results demonstrate that in p53-deficient human gastric cancer cells, restoration
      of functional miR-34 inhibits cell growth and induces chemosensitization and
      apoptosis, indicating that miR-34 may restore p53 function. Restoration of miR-34
      inhibits tumorsphere formation and growth, which is reported to be correlated to
      the self-renewal of cancer stem cells. The mechanism of miR-34-mediated
      suppression of self-renewal appears to be related to the direct modulation of
      downstream targets Bcl-2, Notch, and HMGA2, indicating that miR-34 may be
      involved in gastric cancer stem cell self-renewal/differentiation decision
      making. Our study suggests that restoration of the tumor suppressor miR-34 may
      provide a novel molecular therapy for p53-mutant gastric cancer.

PMID- 18803880
TI  - Malaria prevalence and mosquito net coverage in Oromia and SNNPR regions of
      Ethiopia.
AB  - BACKGROUND: Malaria transmission in Ethiopia is unstable and seasonal, with the
      majority of the country's population living in malaria-prone areas. Results from
      DHS 2005 indicate that the coverage of key malaria interventions was low. The
      government of Ethiopia has set the national goal of full population coverage with
      a mean of 2 long-lasting insecticidal nets (LLINs) per household through
      distribution of about 20 million LLIN by the end of 2007. The aim of this study
      was to generate baseline information on malaria parasite prevalence and coverage
      of key malaria control interventions in Oromia and SNNPR and to relate the
      prevalence survey findings to routine surveillance data just before further mass
      distribution of LLINs. METHODS: A 64 cluster malaria survey was conducted in
      January 2007 using a multi-stage cluster random sampling design. Using Malaria
      Indicator Survey Household Questionnaire modified for the local conditions as
      well as peripheral blood microscopy and rapid diagnostic tests, the survey
      assessed net ownership and use and malaria parasite prevalence in Oromia and
      SNNPR regions of Ethiopia. Routine surveillance data on malaria for the survey
      time period was obtained for comparison with prevalence survey results. RESULTS:
      Overall, 47.5% (95% confidence interval (CI) 33.5-61.9%) of households had at
      least one net, and 35.1% (95% CI 23.1-49.4%) had at least one LLIN. There was no
      difference in net ownership or net utilization between the regions. Malaria
      parasite prevalence was 2.4% (95% CI 1.6-3.5%) overall, but differed markedly
      between the two regions: Oromia, 0.9% (95% CI 0.5-1.6); SNNPR, 5.4% (95% CI 3.4
      8.5), p < 0.001. This difference between the two regions was also reflected in
      the routine surveillance data. CONCLUSION: Household net ownership exhibited
      nearly ten-fold increase compared to the results of Demographic and Health Survey
      2005 when fewer than 5% of households in these two regions owned any nets. The
      results of the survey as well as the routine surveillance data demonstrated that
      malaria continues to be a significant public health challenge in these regions
      and more prevalent in SNNPR than in Oromia.

PMID- 18803881
TI  - A model and typology of collaboration between professionals in healthcare
      organizations.
AB  - BACKGROUND: The new forms of organization of healthcare services entail the
      development of new clinical practices that are grounded in collaboration. Despite
      recent advances in research on the subject of collaboration, there is still a
      need for a better understanding of collaborative processes and for conceptual
      tools to help healthcare professionals develop collaboration amongst themselves
      in complex systems. This study draws on D'Amour's structuration model of
      collaboration to analyze healthcare facilities offering perinatal services in
      four health regions in the province of Quebec. The objectives are to: 1) validate
      the indicators of the structuration model of collaboration; 2) evaluate
      interprofessional and interorganizational collaboration in four health regions;
      and 3) propose a typology of collaboration METHODS: A multiple-case research
      strategy was used. The cases were the healthcare facilities that offer perinatal
      services in four health regions in the province of Quebec (Canada). The data were
      collected through 33 semi-structured interviews with healthcare managers and
      professionals working in the four regions. Written material was also analyzed.
      The data were subjected to a "mixed" inductive-deductive analysis conducted in
      two main stages: an internal analysis of each case followed by a cross-sectional
      analysis of all the cases. RESULTS: The collaboration indicators were shown to be
      valid, although some changes were made to three of them. Analysis of the data
      showed great variation in the level of collaboration between the cases and on
      each dimension. The results suggest a three-level typology of collaboration based
      on the ten indicators: active collaboration, developing collaboration and
      potential collaboration. CONCLUSION: The model and the typology make it possible
      to analyze collaboration and identify areas for improvement. Researchers can use
      the indicators to determine the intensity of collaboration and link it to
      clinical outcomes. Professionals and administrators can use the model to perform
      a diagnostic of collaboration and implement interventions to intensify it.

PMID- 18803882
TI  - Evaluating the performance of Affymetrix SNP Array 6.0 platform with 400 Japanese
      individuals.
AB  - BACKGROUND: With improvements in genotyping technologies, genome-wide association
      studies with hundreds of thousands of SNPs allow the identification of candidate
      genetic loci for multifactorial diseases in different populations. However,
      genotyping errors caused by genotyping platforms or genotype calling algorithms
      may lead to inflation of false associations between markers and phenotypes. In
      addition, the number of SNPs available for genome-wide association studies in the
      Japanese population has been investigated using only 45 samples in the HapMap
      project, which could lead to an inaccurate estimation of the number of SNPs with
      low minor allele frequencies. We genotyped 400 Japanese samples in order to
      estimate the number of SNPs available for genome-wide association studies in the
      Japanese population and to examine the performance of the current SNP Array 6.0
      platform and the genotype calling algorithm "Birdseed". RESULTS: About 20% of the
      909,622 SNP markers on the array were revealed to be monomorphic in the Japanese
      population. Consequently, 661,599 SNPs were available for genome-wide association
      studies in the Japanese population, after excluding the poorly behaving SNPs. The
      Birdseed algorithm accurately determined the genotype calls of each sample with a
      high overall call rate of over 99.5% and a high concordance rate of over 99.8%
      using more than 48 samples after removing low-quality samples by adjusting QC
      criteria. CONCLUSION: Our results confirmed that the SNP Array 6.0 platform
      reached the level reported by the manufacturer, and thus genome-wide association
      studies using the SNP Array 6.0 platform have considerable potential to identify
      candidate susceptibility or resistance genetic factors for multifactorial
      diseases in the Japanese population, as well as in other populations.

PMID- 18803883
TI  - Impact of viral replication inhibition by entecavir on peripheral T lymphocyte
      subpopulations in chronic hepatitis B patients.
AB  - BACKGROUND: To investigate dynamic fluctuations of serum viral load and
      peripheral T-lymphocyte subpopulations of chronic hepatitis B patients and their
      correlation during entecavir therapy. METHODS: Fifty-five patients received
      entecavir 0.5 mg/d therapy. Serum HBV DNA load was measured by Real-Time-PCR, and
      the levels of peripheral T-lymphocyte subpopulations by flow cytometry biweekly,
      every four weeks and every eight weeks during weeks 1-12, 13-24 and 24-48,
      respectively. Multilevel modelling was used to analyse the relationship between
      these variables. RESULTS: Of the 55 patients, all HBeAg positive and with
      detectable HBV DNA, the majority (81.8%) had serum levels of HBV DNA over 10(7)
      copies per milliliter. HBV viral load dropped sharply during the first two weeks.
      In 28 and 43 patients, the level became undetectable from week 24 and 48,
      respectively. Using pre-therapy level as the reference, a significant decrease in
      CD8+ T cells and increase in CD4+ T cells were found from week 12. Both
      parameters and CD4+/CD8+ ratio steadily improved throughout the 48 weeks.
      Multilevel analyses showed that the level of decrement of HBV DNA was associated
      with the increment of T-lymphocyte activities only in the later period (4-48
      week). After 4 weeks of therapy, for each log10 scale decrement of HBV DNA, the
      percentage of CD4+ lymphocyte was increased by 0.49 and that of CD8+ decreased by
      0.51. CONCLUSION: T-lymphocyte subpopulations could be restored partially by
      entecavir treatment in patients with chronic hepatitis B concurrently with
      reduction of viremia.

PMID- 18803884
TI  - Keratin 8 expression in head and neck epithelia.
AB  - BACKGROUND: The intermediate filament forming protein keratin 8 (K8) is a tumour
      associated antigen, which was shown to be over-expressed in a variety of
      malignancies. Here, we present a study of K8 expression in squamous epithelia of
      the head and neck area, including normal mucosa, hyperplastic and dysplastic
      leukoplakia, carcinomas of different sub-localisations, and lymph node
      metastases. METHODS: K8 expression was assessed upon immunohistochemistry with
      specific antibodies in cryosections of primary tumours of the head and neck area.
      RESULTS: K8 expression was characteristic of transformed tissue and marked early
      stages of disease, i.e. dysplastic oral leukoplakia, but not normal or
      hyperplastic epithelium. With the exception of carcinomas of the larynx and the
      tongue, K8 expression also strictly differentiated carcinomas from normal
      epithelium of the same origin. Furthermore, K8high was characteristic of cells,
      which had detached from the sites of primary tumours and had been invading the
      surrounding tissue at the time point of surgery. CONCLUSION: K8 is an excellent
      marker for head and neck malignancies, which allows for early detection as well
      as for visualisation of potentially disseminating tumour cells in vivo.

PMID- 18803885
TI  - Anopheles gambiae complex along The Gambia river, with particular reference to
      the molecular forms of An. gambiae s.s.
AB  - BACKGROUND: The geographic and temporal distribution of M and S molecular forms
      of the major Afrotropical malaria vector species Anopheles gambiae s.s. at the
      western extreme of their range of distribution has never been investigated in
      detail. MATERIALS AND METHODS: Collections of indoor-resting An. gambiae s.l.
      females were carried out along a ca. 400 km west to east transect following the
      River Gambia from the western coastal region of The Gambia to south-eastern
      Senegal during 2005 end of rainy season/early dry season and the 2006 rainy
      season. Specimens were identified to species and molecular forms by PCR-RFLP and
      the origin of blood-meal of fed females was determined by ELISA test. RESULTS:
      Over 4,000 An. gambiae s.l. adult females were collected and identified, 1,041
      and 3,038 in 2005 and 2006, respectively. M-form was mainly found in sympatry
      with Anopheles melas and S-form in the western part of the transect, and with
      Anopheles arabiensis in the central part. S-form was found to prevail in rural
      Sudan-Guinean savannah areas of Eastern Senegal, in sympatry with An. arabiensis.
      Anopheles melas and An. arabiensis relative frequencies were generally lower in
      the rainy season samples, when An. gambiae s.s. was prevailing. No large seasonal
      fluctuations were observed for M and S-forms. In areas where both M and S were
      recorded, the frequency of hybrids between them ranged from to 0.6% to 7%.
      DISCUSSION: The observed pattern of taxa distribution supports the hypothesis of
      a better adaptation of M-form to areas characterized by water-retaining alluvial
      deposits along the Gambia River, characterized by marshy vegetation, mangrove
      woods and rice cultivations. In contrast, the S-form seems to be better adapted
      to free-draining soil, covered with open woodland savannah or farmland, rich in
      temporary larval breeding sites characterizing mainly the eastern part of the
      transect, where the environmental impact of the Gambia River is much less
      profound and agricultural activities are mainly rain-dependent. Very
      interestingly, the observed frequency of hybridization between the molecular
      forms along the whole transect was much higher than has been reported so far for
      other areas. CONCLUSION: The results support a bionomic divergence between the M
      and S-forms, and suggest that the western extreme of An. gambiae s.s.
      geographical distribution may represent an area of higher-than-expected
      hybridization between the two molecular forms.

PMID- 18803887
TI  - Research question or questionable research?

PMID- 18803886
TI  - Recent advances in understanding the molecular basis of group B Streptococcus
      virulence.
AB  - Group B Streptococcus commonly colonises healthy adults without symptoms, yet
      under certain circumstances displays the ability to invade host tissues, evade
      immune detection and cause serious invasive disease. Consequently, Group B
      Streptococcus remains a leading cause of neonatal pneumonia, sepsis and
      meningitis. Here we review recent information on the bacterial factors and
      mechanisms that direct host-pathogen interactions involved in the pathogenesis of
      Group B Streptococcus infection. New research on host signalling and inflammatory
      responses to Group B Streptococcus infection is summarised. An understanding of
      the complex interplay between Group B Streptococcus and host provides valuable
      insight into pathogen evolution and highlights molecular targets for therapeutic
      intervention.

PMID- 18803888
TI  - Effect of diclofenac suppository on tramadol consumption in posthysterectomy
      pain.
AB  - OBJECTIVE: To determine reduction in dose of tramadol and side effects in
      posthysterectomy patients on addition of diclofenac on rectal suppository. STUDY
      DESIGN: Randomized double blinded placebo controlled study. PLACE AND DURATION OF
      STUDY: The Aga Khan University Hospital, Karachi, Pakistan, from August 2004 to
      January 2006. METHODOLOGY: Seventy ASA I and II females, aged 20 and above, who
      underwent elective abdominal hysterectomy, were included in this study. Patients
      received identical looking suppository of either 100 mg diclofenac sodium or
      placebo after induction of anaesthesia and then 12 hourly for 24 hours. General
      anaesthesia was standardized and tramadol was given by patient controlled
      intravenous analgesia delivery system in the recovery. RESULTS: The mean dose +
      SD of tramadol used in first 24 hours was found to be 317 +153 mg in the placebo
      tramadol group compared to 258 +192 mg in the diclofenac-tramadol group (p =
      0.15, 95% CI = 1.24 to -1.34, 6.63). Seventeen (49 %) patients in the placebo
      tramadol group and 14 (40%) in the diclofenac-tramadol group used rescue
      analgesia (p=0.47). Sedation score was similar in both the groups and there was
      no difference in the incidence of nausea and vomiting and use of antiemetics
      between the groups. CONCLUSION: This study did not show any reduction in tramadol
      consumption, given via patient controlled intravenous analgesia when rectal
      suppository of 100 mg diclofenac was added.

PMID- 18803889
TI  - The role of performing life support courses in rural areas in improving pre
      hospital physiologic conditions of patients with penetrating injuries.
AB  - OBJECTIVE: To evaluate the impact of animal model based medical training courses
      for village healthcare workers on prehospital physiologic condition and prognosis
      of patients with penetrating injuries. STUDY DESIGN: Experimental study. PLACE
      AND DURATION OF STUDY: This study was carried out in Mehran city and its
      neighbouring rural districts in western part of Iran from 2002 to 2004.
      METHODOLOGY: Seventy-six village healthcare workers were trained and equipped to
      deliver in-field medical first cares. First group (226 patients) consisted of
      those who received this cares by the trained group and second group (245
      patients) were those who received no in-field cares and were transported directly
      to the trauma center in provincial capital, Ilam. Physiologic Severity Score
      (PSS) was calculated to determine the physiologic condition of patients in both
      groups. RESULTS: The most prevalent cause of trauma in both groups was car
      accidents (61.6%). Controlling of hemorrhage was the most frequent provided
      initial medical care (40.6%). A significant improvement regarding the PSS score
      was observed in the first group of patients compared to the second group (7.505
      vs. 6.799, 95% CI for difference: 0.3 to 0.9). The mortality rates of the first
      and second group of patients were 3% and 7.3%, respectively (p=0.051).
      CONCLUSION: Performing life support courses in rural areas of low-income
      countries where there is no pre-hospital triage and emergency medical system and
      provision of classic resuscitative measures are limited, has a significant impact
      on improvement of pre-hospital physiologic condition and prognosis of patients
      with penetrating injuries.

PMID- 18803890
TI  - Contraceptive knowledge, attitude and practice among rural women.
AB  - OBJECTIVE: To assess the knowledge, attitude regarding family planning and the
      practice of contraceptives among rural women. STUDY DESIGN: A cross-sectional
      observational study. PLACE AND DURATION OF STUDY: The gynaecological outpatient
      clinic of Fatima Hospital, Baqai Medical University, Karachi, from July to
      December 2005. METHODOLOGY: One-hundred women between the ages 15-45, living with
      their husbands and coming from rural area (villages) were interviewed. Women who
      were pregnant, had a child younger than 2 years, or had any medical disorder were
      excluded. Their knowledge, attitude and practice on contraceptives were evaluated
      with the help of a predesigned questionnaire. The other variables used were the
      age of women, parity and educational status. Descriptive analysis was conducted
      to obtain percentages. RESULTS: Out of 100 interviewed women with mean age of
      29.7 years, 81(81%) had some knowledge about family planning methods. The media
      provided information of contraceptives in 52 out of 81 (64%) women. Regarding the
      usage of contraceptive methods, only 53 (53%) of the respondents were using some
      sort of contraception. Barrier method (condoms) was in practice by 18 (33.9%) and
      12 (22.6%) of women had already undergone tubal ligation. The women using
      injectables and intrauterine contraceptive devices were 10 (18.8%) and 7 (13.2%)
      respectively. Six were using oral contraceptive pills (11.3%). Positive attitude
      towards contraception was shown by 76 (76%) of them, while 41(41%) stated their
      husbands' positive attitude towards contraception. CONCLUSION: In the present
      study, there was a low contraceptive use among women of rural origin despite good
      knowledge. Motivation of couples through media and health personnel can help to
      achieve positive attitude of husbands for effective use of contraceptives.

PMID- 18803891
TI  - Comparison of anthracycline-based combination chemotherapy with or without all
      trans retinoic acid in acute promyelocytic leukemia.
AB  - OBJECTIVE: To compare survival in Acute Promyelocytic Leukemia (APL) patients
      treated with or without All-Trans Retinoic Acid (ATRA). STUDY DESIGN:
      Longitudinal, comparative study. PLACE AND DURATION OF STUDY: The Armed Forces
      Bone Marrow Transplant Centre (AFBMTC), Rawalpindi, Pakistan from May 2001 to
      April 2007. METHODOLOGY: All consecutive newly diagnosed patients of acute
      promyelocytic leukemia, treated at Armed Forces Bone Marrow Transplant Centre,
      Rawalpindi, Pakistan, between May 2001 and April 2007, were included and given
      chemotherapy according to availability of ATRA. Diagnosis was confirmed on
      morphology/ karyotyping/ molecular analysis. Eligibility criteria included
      confirmed morphologic diagnosis and/or by demonstration of t(15;17) and/or
      PML/RAR proportional to re-arrangement, no prior chemotherapy, normal hepatic and
      renal function, Eastern Cooperative Oncology Group (ECOG) performance status of 0
      - 2 and no contraindications to ATRA (history of sensitivity to Vit. A or other
      retinoids). All patients having history of cardiac failure (LVEF < 50) and
      arrhythmias, ECOG performance status 3 and 4, relapse / refractory disease, ALT
      twice normal values, serum creatinine > 150 micromol/L and pregnancy were
      excluded from this study. Survival was calculated from the date of chemotherapy
      to death or last follow-up according to Kaplan-Meier and Cox (Proportional
      hazard) regression analysis methods. RESULTS: During the 6 years study period, 31
      newly diagnosed patients with acute promyelocytic leukemia received treatment at
      AFBMTC. Seventeen patients received anthracycline-based remission induction and
      consolidation chemotherapy, while 14 received ATRA-based remission induction,
      consolidation and by two years maintenance therapy. Overall Survival (OS),
      Disease Free Survival (DFS) and mortality were 29.4%, 29.4% and 70.6%
      respectively in 17 patients who received anthracycline based chemotherapy,
      whereas in patients who received ATRA-based chemotherapy OS, DFS and mortality
      was 71.4%, 64.2% and 28.6% respectively. Major causes of mortality were
      septicemia and chemotherapy related toxicity. CONCLUSION: Response to ATRA-based
      chemotherapy in patient cohort was better as compared with anthracycline based
      chemotherapy (71.4% vs. 29.4%) in terms of survival and mortality.

PMID- 18803892
TI  - Intraumbilical veinous injection oxytocin in the active management of third stage
      of labour.
AB  - OBJECTIVE: To determine the role of intraumbilical vein oxytocin reducing blood
      loss during and after one hour of delivery of placenta and its efficacy in
      reducing the frequency of retained placenta. STUDY DESIGN: Randomized controlled
      trial. PLACE AND DURATION OF STUDY: Combined Military Hospital, Multan, from June
      2002 to October 2002. METHODOLOGY: Five hundred parturient women with low risk
      singleton term pregnancy were enrolled in the study. Two hundred and fifty women
      each were included in the study and control group after randomization. The
      patients and health care providers both were blinded to the intervention. Primary
      outcome measures were kept as duration and amount of blood loss in third stage of
      labour. Secondary outcome measures included incidence of retained placenta,
      abdominal need for additional utero-tonics, frequency of postpartum pain, nausea
      and vomiting, fever, need for blood transfusion, establishment of breast feeding
      and total duration of hospital stay. RESULTS: Women in study group who received
      intraumbilical vein syntocinon lost 234.03 ml of blood while the control group
      lost 276.51 ml (p=0.001). Mean duration of third stage was 2.59 minutes in the
      study group and 7.67 minutes in the control group (p<0.001). The frequency of
      retained placenta was 1.2%, which involved only the control group. Abdominal pain
      was experienced by study group but the difference was not found statistically
      significant. Nausea and vomiting was more in study group (p=0.001). No
      discernible difference was found in length of hospital stay, the need for blood
      transfusion, fever and establishment of breast-feeding in both groups.
      CONCLUSION: The addition of intraumbilical vein syntocinon 10 units resulted in
      marked reduction in amount of blood loss, duration of third stage and incidence
      of retained placenta in comparison to intravenous 5 IU oxytocin+0.5 mg
      ergometrine alone.

PMID- 18803893
TI  - Maternal and neonatal complications in term breech delivered vaginally.
AB  - OBJECTIVE: To evaluate the maternal and neonatal complications in terms of
      genital tract trauma to mother, perinatal mortality, Apgar score at 5 minutes and
      neonatal trauma in all singleton term breech cases delivered vaginally. STUDY
      DESIGN: Case series. PLACE AND DURATION OF STUDY: Department of Obstetrics and
      Gynaecology, Bolan Medical Complex Hospital, Quetta, from May 2005 to March 2006.
      METHODOLOGY: A 100 consecutive patients with singleton breech presentation,
      whether booked or unbooked, were admitted and delivered vaginally in hospital
      during the study period. They were studied for maternal and neonatal
      complications. Maternal complication included any genital tract trauma during
      delivery while neonatal complications were perinatal mortality, low Apgar score
      (less than eight at 5 minutes) and birth trauma. RESULTS: There were a total 3977
      deliveries during this study period, 145 breech presentation (incidence 3.6%).
      Out of those, 100 were included in the study. All were unbooked cases, 87% were
      multigravida while 13% were primigravida. An Apgar score of eight was recorded in
      87% babies while 10% had an Apgar score of less than eight after 5 minutes. There
      were 3 still births and one neonatal death. Aggregated perinatal mortality rate
      was 40/1000 live births. Only one baby had birth trauma (Erb's paralysis) during
      vaginal breech delivery. Ninety seven (97%) mothers had no complications while
      only 3 (3%) had complications. Out of these, one had cervical tear and 2 had
      vaginal tears. CONCLUSION: Offering a trial of vaginal breech delivery to
      strictly selected and well-counselled patients remains an appropriate option
      without compromising perinatal and maternal outcome. It also decreases the rate
      of operative delivery for this malpresentation.

PMID- 18803894
TI  - Assessment of psychosocial impact of dental aesthetics.
AB  - OBJECTIVE: To assess the psychosocial impact of dental aesthetics using the
      'Psychosocial Impact of Dental Aesthetics Questionnaire' (PIDAQ) and self-rated
      Aesthetic Component (AC) of the Index of Orthodontic Treatment Need (IOTN). STUDY
      DESIGN: Cross-sectional study. PLACE AND DURATION OF STUDY: Dental Section, the
      Aga Khan University Hospital, Karachi, from August to September 2006.
      METHODOLOGY: Adults with no prior orthodontic treatment were asked to complete a
      modified version of the 'Psychosocial Impact of Dental Aesthetics Questionnaire'
      (PIDAQ). A total of four variables including 'Dental Self-confidence', 'Social
      impact', 'Psychological impact' and 'Perceived orthodontic treatment need' were
      assessed by a series of statements, whereas dental aesthetics were assessed by
      the respondents using the IOTN Aesthetic Component (self-rated IOTN-AC). Kruskal
      Walli's test was applied to determine significance. RESULTS: The respondents were
      120 adults (70 females and 50 males; mean age 25.8 years), all four of the above
      mentioned variables measuring psychosocial impact showed positive and significant
      correlations with the perceived severity of malocclusion as depicted by the
      Aesthetic Component (AC) of Index of Orthodontic Treatment Need (IOTN), with p
      value of less than 0.01 for all variables. CONCLUSION: The results indicate the
      strong psychosocial impact of altered dental aesthetics on the emotional state of
      an individual. The association between self-rated IOTN-AC grading with
      psychosocial well-being stands established, indicating that the perceived
      aesthetics of malocclusion may be as significant a factor in determining
      treatment need as the degree of malocclusion.

PMID- 18803895
TI  - Factor XIII deficiency in children--clinical presentation and outcome.
AB  - OBJECTIVE: To determine the demographic features and clinical outcome of children
      with Factor XIII deficiency. STUDY DESIGN: Observational case series. PLACE AND
      DURATION OF STUDY: The Aga Khan University Hospital, Karachi, from January 1996
      to December 2006. METHODOLOGY: Records of all hospitalized pediatric patients
      with discharge diagnosis of FXIII D, on the basis of factor XIII assay 5 mol/L
      urea test were retrospectively reviewed and abstracted on a pre-specified
      proforma. Demographic features, coagulation profile, family history and outcomes
      were noted. RESULTS: A total of 10 charts were reviewed. There were 5 boys and 5
      girls. Almost all the children (9/10) were less than 5 years of age, out of whom
      5 (50%) were infants, and 3 were neonates. Bruises and prolonged bleeding after
      trauma was the major presenting complaints in 80%, followed by prolonged bleeding
      from the umbilical stump in 2 patients. Nine patients had past history of
      prolonged umbilical bleeding. Two patients had history of FXIII D in siblings,
      while 2 had history of prolonged bleeding in other family members (cause
      unknown). Consanguinity was present in 80% of the families. Initial coagulation
      screen were normal in all patients. Two patients had intracranial hemorrhage,
      proved on neuro-imaging, were managed with plasma infusions and required
      craniotomy. The rest were managed conservatively with plasma transfusions. All
      were discharged alive in good clinical condition. Almost all were followed
      regularly in clinic with monthly cryoprecipitate transfusions. CONCLUSION:
      Although factor XIII deficiency is a rare genetic disorder in children with
      history of bruising, prolonged umbilical bleeding, family history of bleeding and
      consanguinity with normal initial coagulation screen (PT, APTT and platelets),
      FXIII D should be ruled out.

PMID- 18803896
TI  - Frequency of depression and anxiety in patients attending a rheumatology clinic.
AB  - OBJECTIVE: This study was done to find out the frequency of anxiety and
      depression among patients with common rheumatic disorders and determine the
      possible relationship of different demographic and clinical variables with
      anxiety and depression. STUDY DESIGN: Cross-sectional, analytical study. PLACE
      AND DURATION OF STUDY: The study was carried out at Fauji Foundation Hospital,
      Rawalpindi, during April to August 2006. METHODOLOGY: Patients attending the
      rheumatology outpatient department, with more than 2 years duration of rheumatic
      disorder were selected. A proforma regarding the demographic details was filled
      for all the patients. A physician made the assessment regarding the
      rheumatological disorder. Urdu version of Hospital Anxiety and Depression Scale
      (HADS) was used to assess anxiety and depression. Clinical assessment was done by
      two psychiatrists according to International Classification of Diseases-10 (ICD
      10). Data was analyzed on SPSS10 and p-value was calculated using Chi-square test
      as test of significance. RESULTS: There were 108 patients mostly females (90%),
      mean age 44.7 + 11 years, majority (72%) were married and 51% were uneducated.
      Almost 80% of the patients had rheumatoid arthritis. Two-third of the patients
      had persistent symptoms. According to the HADS, scoring 56% of the patients had
      more than the cut off score for depression and 65.7% patients had scores falling
      in the category of cases. Regarding the clinical diagnosis, 42% of the patients
      were found to be depressed. Considering the factors which might be associated
      with depression or anxiety; only gender was found to be significantly associated
      with depression (p=0.03). CONCLUSION: Depression and anxiety is high in patients
      being treated for chronic rheumatological disorders. A close liaison between
      rheumatologist and mental health professionals could prove beneficial for these
      patients.

PMID- 18803897
TI  - Inverted Meckel's diverticulum causing intussusception in an adult.
AB  - Adult intussusception is rare, making-up only about 1% of the causes of bowel
      obstruction intussusception, secondary to an inverted Meckel's diverticulum, is
      also a rare occurrence. Chronic abdominal pain, lower gastrointestinal bleeding,
      and recurrent obstructive symptoms may lead to an unnecessary delay in diagnosis.
      This case report describes a rare cause of adult intestinal intussusception due
      to inverted Meckel's diverticulum. Intussusception was diagnosed on emergency
      ultrasound of the patient, who was successfully managed with surgery.

PMID- 18803898
TI  - Non-secretory myeloma: a rare variant of multiple myeloma.
AB  - The spectrum of plasma cell neoplasm represents indolent conditions like
      Monoclonal Gammopathy of Undetermined Significance (MGUS) to more aggressive
      multiple myeloma and plasma cell leukemia. Non-secretory myeloma comprises less
      than 01% of this spectrum where serum protein electrophoresis and quantitative
      immunoglobulins remain essentially normal. We are presenting a case report of
      this rare variant involving the sternum of an adult male.

PMID- 18803899
TI  - Fine needle aspiration cytology of pseudopapillary tumour of pancreas.
AB  - The solid-cystic pseudopapillary neoplasm is a rare pancreatic tumor having
      indolent course and amenable to complete excision. This is a report of two cases
      of this tumour, diagnosed on fine needle aspiration cytology. One of the cases
      had complete surgical excision of the mass and subsequent histological
      evaluation. This benign and rare neoplasm of pancreas often causes few symptoms.
      The characteristic cytomorphological features point towards the diagnosis.

PMID- 18803900
TI  - Pierre robin sequence as birth asphyxia in a new born.
AB  - A new born baby boy presented with birth asphyxia and respiratory distress. He
      went into cardiac arrest twice but was resuscitated. On detailed evaluation, he
      had low set ears and micrognathia with glossoptosis consistent with features of
      Pierre Robin sequence. Episodes of apnoea disappeared, on nursing, the baby in
      prone position and later on tongue-lip retention suture were applied. Prompt
      diagnosis and efficient airway management by following the principles of airway
      resuscitation can save the lives of such babies without specialized care.

PMID- 18803901
TI  - Primary renal lymphoma.
AB  - A 62-year-old male patient presented with right flank pain and right renal mass
      on CT scan. Patient left against medical advice and had nephrectomy done
      elsewhere. Histopathology revealed a diffuse large cell B-cell lymphoma. Patient
      presented again, with disseminated disease and was started on chemotherapy.
      Although a rare disorder, missing primary renal lymphoma as one of the causes of
      renal mass can lead to disseminated disease and unnecessary nephrectomy, in spite
      of chemotherapy being standard management.

PMID- 18803902
TI  - Rupture of membranes in second trimester of pregnancy.
AB  - The management of rupture of membranes at a nearly viability stage is still
      controversial. A case of a primigravida, who had rupture of membranes at 23 weeks
      of gestation, is reported. On conservative management, her pregnancy continued to
      30 weeks and she delivered a normal fetus, who showed no abnormality till one
      year of follow-up.

PMID- 18803903
TI  - Postpartum cortical blindness.
AB  - A 30-years-old third gravida with previous normal pregnancies and an unremarkable
      prenatal course had an emergency lower segment caesarean section at a periphery
      hospital for failure of labour to progress. She developed bilateral cortical
      blindness immediately after recovery from anesthesia due to cerebral angiopathy
      shown by CT and MR scan as cortical infarct cerebral angiopathy, which is a rare
      complication of a normal pregnancy.

PMID- 18803904
TI  - Increased corneal curvature with posterior nanophthalmos.
AB  - Posterior microphthalmos is a rare condition which is characterized by the
      disproportionately small size of the posterior segment of the eye. The corneal
      diameter, central anterior chamber depth and the lens thickness are all within
      the normal range. We present a case of posterior microphthalmos with all normal
      anterior segment measurements except increased corneal curvature.

PMID- 18803905
TI  - Leiomyoma of the urinary bladder with bladder stone.
AB  - Leiomyoma of the urinary bladder is a rare benign mesenchymal tumour. We describe
      here a case of leiomyoma of the urinary bladder in a 65-year-old gentleman who
      presented with haematuria, passage of clots and combined obstructive and
      irritative urinary symptoms. The investigations revealed a vesical calculus and a
      mass on the left lateral wall of the urinary bladder. Cystolitholapaxy and
      transurethral resection of the tumour was performed. Histopathological report of
      the resected tumour revealed a leiomyoma of the urinary bladder. So far, a
      leiomyoma of the urinary bladder and a concomitant vesical calculus have not been
      described in literature.

PMID- 18803906
TI  - A shell-less chick embryo culturing technique, reproduced successfully under
      local circumstances.

PMID- 18803907
TI  - Ototoxicity--the hidden menace of beta-blockers.

PMID- 18803908
TI  - The unifying dilemma of the Pakistani science journals: an opinion.

PMID- 18803909
TI  - Preserved DNA from past clinical trials yields new information about a subtype of
      alcoholism.

PMID- 18803910
TI  - Use of animal models to develop antiaddiction medications.
AB  - Although addiction is a uniquely human phenomenon, some of its pathognomonic
      features can be modeled at the animal level. Such features include the euphoric
      "high" produced by acute administration of addictive drugs; the dysphoric "crash"
      produced by acute withdrawal; drug-seeking and drug-taking behaviors; and relapse
      to drug-seeking behavior after achieving successful abstinence. Animal models
      exist for each of these features. In this review, I focus on various animal
      models of addiction and how they can be used to search for clinically effective
      antiaddiction medications. I conclude by noting some of the new and novel
      medications that have been developed preclinically using such models and the hope
      for further developments along such lines.

PMID- 18803911
TI  - Use of stimulants to treat cocaine and methamphetamine abuse.
AB  - The concept of using stimulants to treat cocaine and methamphetamine dependence
      is largely based on the "replacement" therapy model that has shown efficacy for
      treating nicotine and opiate dependence. Although results have been mixed, some
      evidence supports using stimulant medication to reduce cocaine use. There are not
      enough data to date to determine the efficacy of stimulants for methamphetamine
      dependence. Drawbacks of stimulants as treatments include the potential for abuse
      of the treatment, which necessitates careful screening and monitoring of
      patients. Possible reasons for efficacy of stimulants include enhancement of
      monoamine function dysregulated by chronic cocaine or methamphetamine use. Newer
      medications that enhance dopamine function but lack the abuse potential of older
      stimulants are being studied. It is hoped that these medications will provide
      safe, effective treatment for cocaine and methamphetamine dependence, but more
      research on this topic is needed.

PMID- 18803912
TI  - Novel medications to treat addictive disorders.
AB  - Recent discoveries about the effects of drugs of abuse on the brain and the
      mechanisms of their addictions; new chemical compounds, including
      immunotherapies; and new actions of available medications are offering many
      opportunities for the discovery and development of novel medications to treat
      addictive disorders. Furthermore, advancements in the understanding of the
      genetic and epigenetic basis of drug addiction and the pharmacogenetics of the
      safety and/or efficacy of the medications are providing opportunities for more
      individualized pharmacotherapy approaches. Although multiple medications have
      been investigated for treating addictions, only a handful have shown acceptable
      safety and efficacy and are approved by the US Food and Drug Administration. This
      article reviews the current medications that are medically safe and have shown
      promising results for treating opioid, cocaine, methamphetamine, and cannabis
      addictions.

PMID- 18803913
TI  - Training physicians to treat substance use disorders.
AB  - The importance of training physicians to effectively assess and manage substance
      use disorders has become increasingly recognized. Studies highlighting the effort
      to enhance curricula are described and common practices identified. Preferable
      curricula incorporate interactive teaching methods along with experiential and
      didactic components. Addiction specialists serve an important role in training
      programs designed for medical students and residents (ie, role models) and
      practicing physicians (ie, clinical support). Further integration of online
      training into current programs may expand and enhance training opportunities.

PMID- 18803914
TI  - ADD/ADHD and Impaired Executive Function in Clinical Practice.
AB  - The disorder currently known as attention-deficit disorder (ADD) or attention
      deficit/hyperactivity disorder (ADHD) is now recognized by most clinicians as a
      legitimate and widely prevalent disorder among children and adults. Yet there is
      still widespread misunderstanding as to the disorder's nature. Many clinicians
      mistakenly continue to think of this as a behavior disorder characterized by
      hyperactivity in children and excessive restlessness or impulsivity in adults. In
      fact, ADD/ADHD is essentially a cognitive disorder, a developmental impairment of
      executive functions (EFs), the self-management system of the brain. Although EFs
      are complex, their impairment constitutes a syndrome that can be recognized
      readily in clinical practice; impaired EF involves a pattern of chronic
      difficulties in executing a wide variety of daily tasks. Once recognized, this
      disorder can be effectively treated in most cases. In this article, I describe
      the nature of EF impairments in ADD/ADHD and how the syndrome can be recognized
      and effectively treated in clinical practice. (Note: The term ADHD is used in the
      balance of this article to refer to both inattentive and combined subtypes.).

PMID- 18803915
TI  - Psychosocial treatments for attention-deficit/hyperactivity disorder.
AB  - Attention-deficit/hyperactivity disorder (ADHD) is a chronic disorder requiring
      developmentally sensitive interventions across the lifespan. Although
      pharmacotherapy traditionally has been considered the first-line treatment for
      ADHD, many individuals continue to experience significant functional impairment
      or choose not to pursue pharmacotherapy. Thus, evidence-based alternatives or
      adjuncts to pharmacologic treatment for individuals with ADHD are needed.
      Behavioral parent training and behavioral school interventions are the only
      empirically supported nonpharmacologic interventions for children and adolescents
      with ADHD. This article reviews recent additions to the ADHD literature,
      including evaluations of behavioral interventions in traditional clinical
      practice and schools, treatment efficacy for preschool-aged children and adults,
      and the investigation of a novel treatment for individuals with the predominantly
      inattentive subtype of ADHD.

PMID- 18803916
TI  - Attention-deficit/hyperactivity disorder and its comorbidities in women and
      girls: an evolving picture.
AB  - Despite the increasing recognition of attention-deficit/hyperactivity disorder
      (ADHD) in females, gender-sensitive comorbidity profiles have been slow to
      develop. In this article, I focus on coexisting conditions in females with ADHD
      and highlight significant differences that deserve greater attention. For some
      time, it has been held that women with ADHD are more likely to internalize
      symptoms and become anxious and depressed and to suffer emotional dysregulation
      than males with the disorder. Recent evidence confirms that girls with ADHD are
      5.4 times more likely to be diagnosed with major depression and three times more
      likely to be treated for depression before their ADHD diagnosis. I also discuss
      eating disorders (particularly binge eating and bulimia) that recently have been
      linked to ADHD in girls and women. The disordered eating/ADHD connection is not
      difficult to understand but has important clinical and therapeutic implications
      that must not be overlooked.

PMID- 18803917
TI  - A clinical review of outcomes of the multimodal treatment study of children with
      attention-deficit/hyperactivity disorder (MTA).
AB  - Over the past decade, the Multimodal Treatment Study of Children with Attention
      Deficit/Hyperactivity Disorder has provided a bewildering wealth of data (more
      than 70 peer-reviewed articles) addressing treatment-related questions for
      children with attention-deficit/hyperactivity disorder. However, the take-home
      messages for clinicians may not always be clear. Therefore, this article reviews
      key findings, including relative benefits of medication and behavioral
      treatments, long-term effects at 2 and 3 years, treatment mediators and
      moderators, preliminary delinquency and substance use outcomes, and growth
      suppression related to stimulant use. Appropriate interpretations of the findings
      and their limitations are discussed, and recommendations for clinical practice
      are derived.

PMID- 18803918
TI  - Quantitative electroencephalography and attention-deficit/hyperactivity disorder:
      implications for clinical practice.
AB  - Although behavioral symptoms of inattention, impulsivity, and hyperactivity serve
      as a foundation for the accurate diagnosis of attention-deficit/hyperactivity
      disorder (ADHD), the low interrater reliability and specificity of behavioral
      rating scales and the absence of comprehensive screening for medical conditions
      that mimic ADHD have created a barrier to the effective treatment of ADHD.
      Recently published studies using quantitative electroencephalographic techniques
      have identified abnormal patterns of cortical activation through power spectral
      analysis, in event-related cortical potentials, and in slow cortical potentials
      that may serve as a basis for overcoming these barriers. This paper reviews the
      initial evidence indicating that power spectral analysis and event-related
      cortical potentials may be useful in differentiating ADHD from other psychiatric
      disorders, helping in medication selection, evaluating medication response, and
      improving the rate of treatment initiation and maintenance. Studies examining
      electroencephalogram biofeedback (neurotherapy) are reviewed using published
      efficacy guidelines.

PMID- 18803919
TI  - Sleep disorders and attention-deficit/hyperactivity disorder.
AB  - The relationship between attention-deficit/hyperactivity disorder (ADHD) and
      sleep is complex and poses many challenges in clinical practice. Recent studies
      have helped to elucidate the nature of the neuromodulator systems underlying the
      associations among sleepiness, arousal, and attention. Studies of sleep
      disturbances in children with academic and behavioral problems have also
      underscored the role that primary sleep disorders play in the clinical
      presentation of symptoms of inattention and behavioral dysregulation. Recent
      research has shed further light on the prevalence, type, risk factors for, and
      impact of sleep disturbances on children with ADHD. The following discussion of
      the multilevel and bidirectional relationships among sleep, neurobehavioral
      functioning, and the clinical syndrome of ADHD synthesizes current knowledge
      about the interaction of sleep and attention/arousal in these children.
      Guidelines are provided to outline a clinical approach to evaluating and managing
      children with ADHD and sleep problems.

PMID- 18803920
TI  - Health-related quality of life according to the main caregiver in patients with
      home nutritional support.
AB  - BACKGROUND AND OBJECTIVE: We intended to know the degree of agreement between the
      quality of life's perception of patients with home nutritional support and that
      of their main caregiver in the different dimensions. We also aimed to establish
      the predictive ability of the health-related quality of life (HRQL) punctuation
      of the caregiver about the patient, fixed up by other variables. METHOD: We
      evaluated the HRQL with the EuroQol-5D (EQ-5D) questionnaire in 245 patients by
      means of a direct interview with them and with their main caregiver. The patients
      came from 13 hospitals of the National Health System and they were selected
      sequentially according to their visits to the hospital or at home. RESULTS: The
      agreement obtained in the EQ-5D components was high, except for the anxiety
      component, which had a 58% concordance (McNemar's test, p = 0.005; kappa = 0.340,
      p < 0.001). When studying the agreement between the patient punctuation and that
      of the main caregiver, an intraclass correlation coefficient (ICC) = 0.887 (95%
      confidence interval [CI], 0.852-0.913) was obtained. When studying the predictive
      ability of the caregiver's punctuation about the patient, we obtained an R2 =
      0.649 with a regression coefficient of 0.803 (95% CI, 0.725-0.882) in the EQ-5D,
      while in the visual analogical scale an ICC = 0.823 (95% CI, 0.771-0.863) was
      obtained, and an R2 = 0.475 with a regression coefficient of 0.719 (95% CI, 0.617
      0.822) was found. CONCLUSIONS: A caregiver's evaluation can be useful to have an
      approximation to the patient's perception when he/she does not have the ability
      to communicate. The approach is better if we consider the variables sex,
      pathological group, age of the caregiver or the evaluation of changes in the
      health state for the last 12 months.

PMID- 18803921
TI  - [Usefulness of transcranial sonography in Parkinson's disease. A comparative
      study using 123I-FP-CIT SPECT].
AB  - BACKGROUND AND OBJECTIVE: An increased echogenicity of the substantia nigra in
      patients with Parkinson's disease has been demonstrated by brain parenchyma
      sonography (BPS). BPS is a new and non-invasive technique that allows imaging of
      the brain in 2-dimensional axial slices. Changes in echogenicity can be displayed
      using ultrasounds. The aim of this study is to evaluate substantia nigra
      echogenicity in a group of Parkinson's disease patients and controls and compare
      with disease and functional neuroimaging parameters using ioflupane-single photon
      emission computed tomography (SPECT). PATIENTS AND METHOD: Fourty-two subjects
      were recruited consecutively. BPS and ioflupane-SPECT were performed in all.
      RESULTS: Around 90% of Parkinson's disease patients showed a distinctive increase
      of echogenicity of substantia nigra above or equal 0.18 cm2, whereas this echo
      feature was detected in 11% of controls. Most of patients (86%) with an area of
      substantia nigra echogenicity above or equal 0.18 cm2 showed a nigro-striatal
      impairment, that is, a decreased ioflupane uptake measured by SPECT. CONCLUSIONS:
      BPS is a useful tool in the diagnosis of Parkinson's disease. A good agreement
      between both techniques was achieved. The diagnosis accuracy obtained using BPS
      does not seem superior to ioflupane-SPECT. Nevertheless, hyperechogenicity could
      be considered as a vulnerability "marker" of the substantia nigra.

PMID- 18803922
TI  - [Intravenous antibiotic treatment in a hospital based home care unit. Predictors
      of hospital readmission].
AB  - BACKGROUND AND OBJECTIVE: Intravenous antibiotic therapy at home has showed its
      efficacy as an alternative to hospitalization care in many infectious
      pathologies. The objectives of this study are: a) to expose our experience, as
      hospital at home unit (HHU) integrated within a service of internal medicine, in
      the antibiotic treatment, and b) to define those parameters that can predict
      hospital readmissions. PATIENTS AND METHOD: This study included all patients with
      infectious pathology and intravenous antibiotic therapy who were admitted in our
      HHU from March 2006 to March 2007. RESULTS: 145 patients were included in this
      study. Successful treatment was observed in 92% of patients. Eleven patients were
      re-admitted at hospital during the episode by infectious disease, and only 2 of
      them showed adverse effects to treatment. Twenty-two patients were re-admitted at
      hospital 3 months after due to chronic pathology. CONCLUSIONS: Intravenous
      antibiotic therapy at home is a good alternative in many infectious pathologies.
      Infectious pathology and baseline state can be predictors of hospital
      readmissions.

PMID- 18803923
TI  - [Home nutritional support: a step towards humanization].

PMID- 18803924
TI  - [Home intravenous antimicrobial therapy].

PMID- 18803925
TI  - [Automated erythrocytapheresis as treatment of severe malaria. Study of 6
      patients].
AB  - BACKGROUND AND OBJECTIVE: The high mortality attributable to severe malaria by
      Plasmodium falciparum is related to the grade of parasitemia. Automated
      erithrocytapheresis (AE) is a safe alternative to exchange transfussion, with the
      same potential benefits but less undesirable side effects. Literature on this
      technique is scarce, consisting of isolated reports or short series. The
      objective of this study is to describe the clinical picture and outcome observed
      in 6 severely ill malaria patients in whom EA was applied as complimentary
      therapeutic technique. PATIENTS AND METHOD: An observational prospective
      descriptive study was carried out of all inpatients with severe malaria in a
      single hospital between 1996 and 2006 in whom clinical, epidemiological and
      parsitological data were analyzed. RESULTS: This series included 2 women and 4
      men, with a median age of 43 years. In all cases, the infection was acquired in
      West Sub-Saharan Africa. No patient had received antimalarial prophylaxis and all
      were infected by Plasmodium falciparum. The grade of parasitemia was between 10%
      and 35%. The number of severity criteria was between one and 4, the more frequent
      being hyperbilirrubinemia. All patients received conventional intravenous
      treatment. The total length of admission oscillated between 5 and 37 days, while
      the length of stay in the Intensive Care Unit varied between one and 17 days. All
      patients survived. CONCLUSIONS: AE is a safe technique, with the same advantages
      that blood exchange but lacking many of its disadvantages. A isolated parasitemia
      above 10%, or when a parasitaemia above of 5% is associated with any additional
      World Health Organization-2000 criteria of clinical severity, should constitute
      an indication for AE.

PMID- 18803926
TI  - [Critical review and proposals for improvement of the health information systems
      on cardiovascular diseases in Spain].

PMID- 18803927
TI  - [Surface enhanced laser desorption/ionization (SELDI): proteomics technology and
      its application in oncology].
AB  - Proteomic is the study of proteomes and it involves the global analysis of
      protein expression profiles, the identification of them and their function in any
      tissue, organ or organism. Oncoproteomic is the application of proteomics
      technologies in oncology, which promises to accelerate the discovery of new
      therapeutics targets and useful biomarkers for diagnosis, prognostic and medical
      treatment of diverse diseases including cancer. In this context, SELDI (surface
      enhanced laser desorption-ionization) is one of the more used techniques for the
      development of new tools with clinical utility, among them the discovery of new
      biomarker molecules that could serve as indicators of both physiological and
      disease states. This review covers general aspects of the proteomic techniques
      and particularly we describe the findings of some studies that used SELDI for the
      generation of proteomic patterns in order to identify potential biomarkers
      associated with the diagnosis and prognosis of a variety of cancers.

PMID- 18803928
TI  - [Availability of hydroxicobalamin as an antidote for patients intoxicated by fire
      smoke in Spanish hospitals].

PMID- 18803929
TI  - [Disability by low back pain in Spain from 2000 to 2004].

PMID- 18803930
TI  - [Toxic epidermal necrolysis].

PMID- 18803931
TI  - Adaptive strategies of Yersinia pestis to persist during inter-epizootic and
      epizootic periods.
AB  - Plague is a flea-borne zoonotic bacterial disease caused by Yersinia pestis. It
      has caused three historical pandemics, including the Black Death which killed
      nearly a third of Europe's population in the 14th century. In modern times,
      plague epizootics can extirpate entire susceptible wildlife populations and then
      disappear for long time periods. Understanding how Y. pestis is maintained during
      inter-epizootic periods and the factors responsible for transitioning to
      epizootics is important for preventing and controlling pathogen transmission and
      ultimately reducing the burden of human disease. In this review, we focus
      primarily on plague in North American foci and discuss the potential adaptive
      strategies Y. pestis might employ to ensure not only its survival during inter
      epizootic periods but also the rapid epizootic spread and invasion of new
      territories that are so characteristic of plague and have resulted in major
      pandemics and establishment of plague foci throughout much of the world.

PMID- 18803932
TI  - Independent and opposite associations of hip and waist circumference with
      metabolic syndrome components and with inflammatory and atherothrombotic risk
      factors in overweight and obese women.
AB  - Recent studies have shown independent and opposite associations of hip
      circumference (HC) and waist circumference (WC) with glucose intolerance, insulin
      resistance, and type 2 diabetes mellitus. However, no studies have simultaneously
      considered the independent contributions of both markers to metabolic
      proinflammatory and atherosclerotic risk factors. In this study, we examine the
      independent associations of WC and HC with metabolic syndrome and with
      proinflammatory and atherothrombotic features. Independent associations of thigh
      muscle and adipose tissue (AT) compartments with metabolic features were also
      studied. Abdominal and thigh muscle and AT distributions were assessed by
      computed tomography in 140 overweight and obese women (mean +/- SD: age, 38.3 +/-
      0.5 years; body mass index, 30.4 +/- 0.3 kg/m(2)). Blood lipids and inflammatory
      and atherothrombotic markers were measured. For a given WC, a larger HC was
      inversely associated with fasting insulin (beta = -0.288, P = .008), hemoglobin
      A(1c) (beta = -0.246, P = .041), and plasminogen activator inhibitor-1
      concentrations (beta = -0.241, P = .023). Contrarily, WC was related with an
      unfavorable metabolic profile. For a given WC, higher total thigh AT and total
      thigh subcutaneous AT masses were associated with lower hemoglobin A(1c) (beta = 
      0.244, P = .049; beta = -0.233, P = .049) and low-density lipoprotein cholesterol
      to high-density lipoprotein cholesterol ratio (beta = -0.252, P = .040; beta = 
      0.245, P = .037). In addition, total thigh AT was related with leptin (beta =
      0.310, P = .012), whereas total thigh subcutaneous AT revealed opposite
      associations with fasting insulin concentrations (beta = -0.239, P = .034). Total
      thigh muscular tissue mass was related with lower plasminogen activator inhibitor
      1 (beta = -0.164, P = .049) and fibrinogen concentrations (beta = -0.222, P =
      .018). In conclusion, HC revealed independent and opposite associations with
      insulin resistance and atherothrombotic disturbances. Contrarily, a larger WC
      predicted an increased metabolic risk. These contrasting effects in diabetogenic
      and atherothrombotic disturbances were, respectively, mediated by gluteofemoral
      AT and thigh muscle tissue. Besides body mass index and WC screening relevance,
      HC can contribute to additionally predict health risk in overweight and obese
      women.

PMID- 18803933
TI  - Lipoprotein (a) as a risk factor for silent cerebral infarction in hemodialysis
      patients.
AB  - In patients with chronic renal failure undergoing hemodialysis (HD), silent
      cerebral infarctions (SCIs) are associated with high mortality. Levels of
      lipoprotein (a) (Lp[a]) increase with renal dysfunction and may be a novel
      predictor for cerebrovascular events. We tested the hypothesis that increased
      Lp(a) levels correlate with the occurrence of SCI in HD patients. Using cranial
      magnetic resonance imaging findings, we divided 62 Japanese patients undergoing
      HD into with-SCI group (61 +/- 7 years, mean +/- SD, n = 34) and without-SCI
      group (60 +/- 6 years, n = 28). We compared the sex, body mass index, metabolic
      profiles, Lp(a) levels, and smoking habits between the 2 groups. The following
      observations were noted: (1) The number of patients with diabetes or hypertension
      did not differ between the 2 groups. (2) The levels of Lp(a) were higher in the
      with-SCI group in comparison with the without-SCI group (P < .0001). (3) The
      proportion of smokers was higher in the with-SCI group than in the without-SCI
      group (P < .05). (4) Plasma levels of high-density lipoprotein cholesterol were
      lower, whereas uric acid was higher, in the with-SCI group than in the without
      SCI group (P < .001 and P < .05, respectively). (5) Multiple logistic regression
      analysis identified Lp(a) levels as being significantly associated with the
      presence of SCI (odds ratio, 1.23; 95% confidence interval, 1.09-1.38; P <
      .0001). This study indicates that patients with chronic renal failure, who are
      maintained on HD, exhibit an increased prevalence of SCI and that Lp(a) is
      significantly associated with the presence of SCI in HD patients.

PMID- 18803934
TI  - The role of fatty acids and caveolin-1 in tumor necrosis factor alpha-induced
      endothelial cell activation.
AB  - Hypertriglyceridemia and associated high circulating free fatty acids are
      important risk factors for atherosclerosis. In contrast to omega-3 fatty acids,
      linoleic acid, the major omega-6 unsaturated fatty acid in the American diet, may
      be atherogenic by amplifying an endothelial inflammatory response. We hypothesize
      that omega-6 and omega-3 fatty acids can differentially modulate tumor necrosis
      factor alpha (TNF-alpha)-induced endothelial cell activation and that functional
      plasma membrane microdomains called caveolae are required for endothelial cell
      activation. Caveolae are particularly abundant in endothelial cells and play a
      major role in endothelial trafficking and the regulation of signaling pathways
      associated with the pathology of vascular diseases. To test our hypothesis,
      endothelial cells were preenriched with either linoleic acid or alpha-linolenic
      acid before TNF-alpha-induced endothelial activation. Measurements included
      oxidative stress and nuclear factor kappaB-dependent induction of cyclooxygenase
      2 (COX-2) and prostaglandin E(2) (PGE(2)) under experimental conditions with
      intact caveolae and with cells in which caveolin-1 was silenced by small
      interfering RNA. Exposure to TNF-alpha induced oxidative stress and inflammatory
      mediators, such as p38 mitogen-activated protein kinase (MAPK), nuclear factor
      kappaB, COX-2, and PGE(2), which were all amplified by preenrichment with
      linoleic acid but blocked or reduced by alpha-linolenic acid. The p38 MAPK
      inhibitor SB203580 blocked TNF-alpha-mediated induction of COX-2 protein
      expression, suggesting a regulatory mechanism through p38 MAPK signaling. Image
      overlay demonstrated TNF-alpha-induced colocalization of TNF receptor type 1 with
      caveolin-1. Caveolin-1 was significantly induced by TNF-alpha, which was further
      amplified by linoleic acid and blocked by alpha-linolenic acid. Furthermore,
      silencing of the caveolin-1 gene completely blocked TNF-alpha-induced production
      of COX-2 and PGE(2) and significantly reduced the amplified response of linoleic
      acid plus TNF-alpha. These data suggest that omega-6 and omega-3 fatty acids can
      differentially modulate TNF-alpha-induced inflammatory stimuli and that caveolae
      and its fatty acid composition play a regulatory role during TNF-alpha-induced
      endothelial cell activation and inflammation.

PMID- 18803935
TI  - Retinol binding protein 4 concentrations are influenced by renal function in
      patients with type 2 diabetes mellitus.
AB  - Retinol binding protein 4 (RBP-4), a newly discovered adipocytokine, has been
      involved in glucose and lipid metabolism. We assess the impacts of renal function
      on plasma RBP-4 levels in patients with type 2 diabetes mellitus with a wide
      range of nephropathy. Plasma RBP-4 levels were measured using the enzyme
      immunoassay method in 38 type 2 diabetes mellitus patients with nephropathy and
      were compared with those in 20 patients with normoalbuminuria. The levels of
      plasma RBP-4 were increased by 1.4- and 3.3-fold in patients with renal disease
      with macroalbuminuria (P = .04) and end-stage renal disease (plasma creatinine
      level >2.0 mg/dL) (P < .0001) compared with those in patients with normal renal
      function. In addition, RBP-4 levels were correlated with the creatinine level and
      24-hour creatinine clearance (Ccr) on simple and multiple regression analyses in
      all patients. Furthermore, in patients having Ccr of more than 60 mL/min, RBP-4
      levels were correlated with the homeostasis model assessment (HOMA)-r index and
      triglyceride (TGL) both on simple and multiple regression analyses.
      Interestingly, in patients having Ccr of less than 60 mL/min, RBP-4 levels were
      not correlated with the HOMA-r index and TGL on simple regression analysis. The
      RBP-4 concentrations are influenced by renal function in type 2 diabetes mellitus
      patients. In addition, RBP-4 levels were correlated with HOMA-r and TGL in
      diabetic subjects without end-stage renal disease.

PMID- 18803936
TI  - The effect of glucose ingestion on inflammation and oxidative stress in obese
      individuals.
AB  - Ingestion of 75 g glucose during an oral glucose tolerance test (OGTT) increases
      systemic inflammation and oxidative stress in healthy subjects and patients with
      type 2 diabetes mellitus, but the effect in overweight/obese nondiabetic
      individuals is uncertain. The aim of the present study was to determine the
      effect of an OGTT on plasma concentrations of inflammatory cytokines and
      peroxides in 33 subjects with body mass index >27 kg/m(2). After an overnight
      fast, blood samples were taken from participants immediately before and at 30,
      60, 90, and 120 minutes after ingestion of 75 g glucose. Plasma glucose, insulin,
      free fatty acid, interleukin (IL)-6, tumor necrosis factor alpha, and peroxides
      were measured during the tests. Plasma IL-6 concentrations decreased (13%)
      significantly (P < .001) at 30 and 60 minutes, whereas plasma peroxide
      concentrations decreased slightly (3%, P = .003) at 30 minutes during the tests.
      The 30-minute decrease in plasma IL-6 was correlated significantly and inversely
      with the concomitant increase in plasma insulin (r = -0.410, P = .02) and with
      the ratio of insulin to glucose at 30 minutes during the OGTT (r = -0.366, P =
      .04). These data suggest that plasma concentrations of IL-6 are acutely decreased
      possibly because of the predominance of the anti-inflammatory effect of
      hyperinsulinemia over the proinflammatory effect of hyperglycemia after ingestion
      of a large quantity of glucose in obese individuals.

PMID- 18803937
TI  - Involvement of low adiponectin levels in impaired glucose tolerance.
AB  - To investigate the association between serum adiponectin levels and 2-hour post
      75-g oral glucose load glycemia, we conducted 75-g oral glucose tolerance tests
      in 50 subjects who had been diagnosed as having impaired glucose tolerance (IGT)
      within the prior 3 years. When adjusted for age, body mass index, and sex, serum
      adiponectin levels in the IGT and diabetes mellitus groups were significantly
      lower than those in the normal glucose tolerance and impaired fasting glucose
      groups (P < .0001). To determine which variables had significant impacts on 2
      hour post-oral glucose glycemia, we performed multiple regression analyses. In
      stepwise analysis, serum adiponectin levels showed the highest F value (F =
      6.43), suggesting the adiponectin level to be an independent predictor of 2-hour
      post-oral glucose glycemia. Thus, our clinical data suggest the involvement of
      low adiponectin levels in IGT and diabetes mellitus. To further assess this
      possibility, we prepared mice fed a high-fat diet for 2 months as an IGT model.
      Afterward, we compared the 2-hour postglucose glycemia in the IGT mice
      overexpressing recombinant adiponectin with that in control IGT mice. Mice
      overexpressing adiponectin showed significantly blunted 2-hour postglucose
      glycemia (5.66 +/- 0.39 mmol/L) as compared with control mice (8.52 +/- 0.67
      mmol/L), whereas fasting glycemia was not significantly altered by adiponectin
      overexpression. Taken together, our results reveal the plasma glucose level in
      response to a glucose load to be negatively associated with serum adiponectin
      levels, suggesting low adiponectin levels to be one of the predictors of abnormal
      glucose homeostasis in IGT.

PMID- 18803938
TI  - Differential effects of insulin sensitivity on androgens in obese women with
      polycystic ovary syndrome or normal ovulation.
AB  - The differential effects of insulin sensitivity and adiposity on androgen
      concentrations in women with polycystic ovary syndrome (PCOS) are unclear. To
      address this issue, we divided 43 overweight women into 4 groups based on both
      their clinical classification (PCOS or normal) and whether they were insulin
      resistant (IR) or insulin sensitive (IS) by their steady-state plasma glucose
      concentrations. Total testosterone concentrations were significantly increased as
      a function of both clinical classification (PCOS vs normal, P < .0001) and steady
      state plasma glucose concentration (IR vs IS, P = .002). Mean testosterone
      concentrations were higher in PCOS-IR compared with PCOS-IS, normal-IR, or normal
      IS women (P < .005). In addition, there was a statistically significant
      interaction (P = .03) between clinical classification (PCOS vs normal) and
      insulin sensitivity (IR vs IS) for testosterone concentrations. In contrast,
      androstenedione concentrations were higher in women with PCOS (P = .001),
      irrespective of whether they were IR or IS (P = .31); and no interaction between
      clinical classification and insulin sensitivity was discerned (P = .34). These
      results indicate that both PCOS and insulin resistance independently contributed
      to increased total testosterone concentrations within a group of overweight/obese
      women. These findings are consistent with the hypothesis that the ovaries of
      women with PCOS are hypersensitive to the ability of insulin to increase
      testosterone production and that the more insulin resistant the patient, the
      higher the testosterone concentration. In contrast, androstenedione
      concentrations seem to be independent of differences in insulin resistance. Our
      findings emphasize the need to increase understanding of the factors that
      modulate ovarian androgen secretion.

PMID- 18803939
TI  - Plasma carboxyl ester lipase activity modulates apolipoprotein B-containing
      lipoprotein metabolism in a transgenic mouse model.
AB  - Pancreatic carboxyl ester lipase (CEL) is in the plasma of many mammals,
      including humans and rats, but not mice. In vitro, CEL hydrolyzes cholesterol
      esters of apolipoprotein B-containing lipoproteins (apo B-Lp). To study the
      effect of CEL on metabolism of apo B-Lp and atherosclerosis in vivo, apo E
      knockout (EKO) mice, which have high plasma levels of apo B-Lp and are prone to
      atherosclerosis, were made to secrete CEL into plasma by introducing a transgene
      containing a liver-specific promoter and rat CEL complementary DNA. Plasma CEL
      activity in EKO-CEL mice was comparable with that found in rats. Evidence of
      modification of apo B-Lp by plasma CEL in vivo was an increase in the free
      cholesterol to cholesterol ester ratio of apo B-Lp from mice on chow or a Western
      type diet. In addition, plasma total cholesterol levels were elevated in EKO-CEL
      mice, with the elevation found exclusively in the apo B-Lp fraction. Associated
      with the increase in steady-state apo B-Lp levels was an increase in the plasma
      half-life of very low-density lipoproteins (VLDL) in EKO-CEL mice, measured by
      the clearance rate of injected VLDL. Interestingly, despite the increase of apo B
      Lp, the atherosclerotic lesion did not differ between EKO and EKO-CEL mice on a
      Western-type diet. In summary, our results demonstrate that plasma CEL modulates
      apo B-Lp metabolism in vivo, resulting in reduced VLDL clearance and elevated
      plasma cholesterol levels.

PMID- 18803940
TI  - Lipoperoxidation and hemodialysis.
AB  - It has been suggested that hemodialysis patients may be under increased oxidative
      stress and may therefore benefit from the long-term use of antioxidants
      (particularly for the reduction of the risk of heart disease). The aim of this
      study was, first, to evaluate the effect of hemodialysis by itself on lipid and
      lipoprotein oxidation profiles and, second, to analyze the effect of vitamin C
      supplementation in patients with end-stage renal disease starting hemodialysis.
      Forty-one patients with end-stage renal disease were enrolled and randomized to
      receive 1000 mg/d vitamin C or matching placebo before starting hemodialysis. We
      measured lipid profile and the susceptibility of low-density lipoprotein (LDL)
      and high-density lipoprotein (HDL) to oxidation using copper ions at the moment
      of inclusion and after 1 year. All lipoperoxidation parameters were included.
      Hemodialysis by itself improved the lipid profile, lowering total cholesterol
      (176.4 +/- 48.4 to 154.2 +/- 28.8 mg/dL, P < .01), LDL cholesterol (94.1 +/- 39.6
      to 76.1 +/- 26.6 mg/dL LDL, P < .03), and phospholipids levels (196.5 +/- 36.7 to
      182.9 +/- 36.1 mg/dL, P < .05) in all patients on maintenance hemodialysis. The
      HDL cholesterol was also decreased (49.4 +/- 19.8 to 43.4 +/- 24.1 mg/dL HDL, P <
      .03). No significant differences were detected between patients receiving vitamin
      C and those receiving placebo. Thiobarbituric acid reactive substances (TBARS)
      and lipoperoxides increased in patients after a year of hemodialysis, but the
      difference was lower in those administered vitamin C for a year-TBARS LDL (in
      nanograms per gram LDL): 0.25 +/- 0.20 to 0.38 +/- 0.2 in vitamin C-treated
      subjects and 0.28 +/- 0.17 to 0.46 +/- 0.21 in those treated with placebo (P <
      .007); TBARS HDL (in nanograms per gram HDL): 0.22 +/- 0.12 to 0.34 +/- 0.30 in
      patients receiving vitamin C and 0.20 +/- 0.18 to 0.28 +/- 0.19 in those
      receiving placebo (P = .071). Hemodialysis by itself seems to improve the lipid
      profile in patients with a previous prooxidative state such as uremia. Although
      our results failed to demonstrate significant differences between vitamin C
      treated and untreated patients, and despite the small number of patients, the
      trend toward a decrease in oxidation products due to vitamin C supplementation
      may be beneficial for oxidation parameters. This area remains controversial and
      under active investigation. Further research is necessary before a firm
      conclusion can be reached.

PMID- 18803941
TI  - White blood cell count and abdominal fat distribution in female obese
      adolescents.
AB  - The association between abdominal fat distribution and inflammatory markers is
      currently a subject of debate. Here, we delineate the relationship between white
      blood cell (WBC) counts and abdominal fat distribution in female obese
      adolescents. A total of 102 female obese adolescent subjects were analyzed.
      Anthropometry, WBC count, blood pressure, fasting plasma glucose, lipid profiles,
      and fasting insulin concentrations were measured. Subcutaneous adipose tissue
      (SAT) and visceral adipose tissue areas were calculated using computed
      tomography. Mean values of waist circumference (P < .05), total adipose tissue
      (TAT) (P < .01), and SAT (P < .01) were significantly higher in the group with
      the higher WBC count. The WBC count was positively related to body mass index,
      waist circumference, and TAT and SAT areas after adjustment for age and metabolic
      risk factors (P < .01). Among the WBC components, neutrophils were positively
      associated with body mass index (P < .01), waist circumference (P < .01), and TAT
      (P < .05). The WBC count escalated with a graded increase in TAT or SAT (P for
      trend < .01). Our findings collectively indicate that the WBC count is positively
      related to abdominal adiposity in female obese adolescents. Moreover, this
      relationship is more distinguishable with subcutaneous than visceral adiposity.

PMID- 18803942
TI  - Change of visfatin, C-reactive protein concentrations, and insulin sensitivity in
      patients with hyperthyroidism.
AB  - The present study was undertaken to evaluate the change of circulating visfatin,
      C-reactive protein (CRP) concentrations, and insulin sensitivity in patients with
      hyperthyroidism. We studied 19 adult patients (14 women and 5 men aged 32.6 +/-
      1.8 years) with hyperthyroidism due to Graves disease and 19 age- and sex-matched
      euthyroid controls (17 women and 2 men aged 36.7 +/- 2.7 years). All hyperthyroid
      patients were treated with 1 of 2 antithyroid drugs and were reevaluated after
      thyroid function normalized. Before antithyroid treatment, the hyperthyroid group
      had significantly higher visfatin plasma concentration (mean +/- standard error
      of the mean, 20.7 +/- 1.8 ng/mL) than the control group (16.2 +/- 1.3 ng/mL, P =
      .044); but the visfatin level dropped significantly after treatment (12.0 +/- 1.4
      ng/mL, P < .001). The reciprocal index of homeostasis model assessment of insulin
      resistance (HOMA-IR) in the hyperthyroid group was higher before treatment (2.06
      +/- 0.26 mmol mU/L*L) than after treatment (1.21 +/- 0.16 mmol mU/L*L, P = .027).
      There was no significant difference in serum glucose, high-sensitivity CRP, and
      insulin levels between hyperthyroid and control groups and in the hyperthyroid
      group before and after treatment. Body mass index-adjusted visfatin levels were
      significantly elevated in the hyperthyroid group. Pearson correlation revealed
      that visfatin, glucose, insulin, and HOMA-IR values positively correlated with
      triiodothyronine and free thyroxine levels. However, visfatin did not correlate
      with insulin and HOMA-IR levels. The results indicated that plasma visfatin
      concentration was elevated in hyperthyroidism due to Graves disease, but serum
      CRP levels were not. Plasma visfatin levels were not associated with indicators
      of insulin resistance in hyperthyroid patients.

PMID- 18803943
TI  - Evaluation of antioxidant systems (coenzyme Q10 and total antioxidant capacity)
      in morbid obesity before and after biliopancreatic diversion.
AB  - Biliopancreatic diversion (BPD) is a surgical procedure performed in patients
      with untreatable obesity and insulin resistance. The demonstrated metabolic and
      hormonal results of this procedure include the reversal of insulin resistance; an
      increase in diet-induced thermogenesis; and modifications of gut hormones, such
      as gastrin, enteroglucagon, neurotensin, and cholecystokinin. On the other hand,
      obesity is a condition of increased oxidative stress; however, few studies have
      investigated antioxidant systems in obese persons with BPD. To evaluate the
      metabolic status and antioxidant systems in such patients, we studied a group of
      11 morbidly obese patients, aged 28 to 62 years, with a mean body mass index
      (BMI) of 54.71 +/- 2.52 kg/m(2), before and after successful BPD (mean post-BPD
      BMI, 44.68 +/- 1.51 kg/m(2)). A control group composed of 10 slightly overweight
      women, with a mean BMI of 28.5 +/- 0.72 kg/m(2), was also studied. Coenzyme Q(10)
      (CoQ(10)) levels (also normalized for cholesterol levels) and total antioxidant
      capacity in blood plasma were assessed in these populations. The most striking
      datum was the extremely low level of CoQ(10) in postoperative period (0.34 +/-
      0.16 vs 0.66 +/- 0.09 mug/mL, P = .04); also, the data corrected for cholesterol
      levels presented the same pattern, with a more marked significance (152.46 +/-
      11.13 vs 186.4 +/- 17.98 nmol/mmol, P = .001). This could be due to lipid
      malabsorption after surgery. In fact, the pre-BPD data present all the metabolic
      and hormonal characteristics of severe obesity; and after BPD, there was a net
      improvement in the metabolic parameters. The first pathophysiologic phenomenon
      seems to be lipid malabsorption that has been argued to be the cause of insulin
      resistance reversion. This metabolic interpretation is also confirmed by the
      absence of significant variations of total antioxidant capacity (57.5 +/- 5.3 vs
      66 +/- 5.3). The mechanisms of these phenomena remain to be established. These
      data suggest the importance of correcting postsurgical metabolic complications,
      in these clinical populations, with CoQ(10) supplementation.

PMID- 18803944
TI  - Insulin-stimulated release of D-chiro-inositol-containing inositolphosphoglycan
      mediator correlates with insulin sensitivity in women with polycystic ovary
      syndrome.
AB  - Some actions of insulin are mediated by inositolphosphoglycan (IPG) mediators.
      Deficient release of a putative D-chiro-inositol-containing (DCI) IPG mediator
      may contribute to insulin resistance in women with polycystic ovary syndrome
      (PCOS). Previously, we demonstrated that oral DCI supplementation improved
      ovulation and metabolic parameters in women with PCOS. However, whether oral DCI
      mediates an increase in the release of the DCI-IPG mediator and an improvement in
      insulin sensitivity in women with PCOS is unknown. We conducted a randomized
      controlled trial of DCI supplementation vs placebo in 11 women with PCOS who were
      assessed at 2 time points 6 weeks apart. Plasma DCI, DCI-IPG release during oral
      glucose tolerance test (AUC(DCI-IPG)), and insulin sensitivity (S(i)) by
      frequently sampled intravenous glucose tolerance test were assessed at baseline
      and end of study. The study was terminated early because of a sudden
      unavailability of the study drug. However, in all subjects without regard to
      treatment assignment, there was a positive correlation between the change in
      AUC(DCI-IPG)/AUC(insulin) ratio and the change in S(i) during the 6-week period
      (r = 0.69, P = .02), which remained significant after adjustment for body mass
      index (P = .022) and after further adjustment for body mass index and treatment
      allocation (P = .0261). This suggests that, in women with PCOS, increased glucose
      stimulated DCI-IPG release is significantly correlated with improved insulin
      sensitivity. The significant relationship between DCI-IPG release and insulin
      sensitivity suggests that the DCI-IPG mediator may be a target for therapeutic
      interventions in PCOS.

PMID- 18803945
TI  - The influence of two variants in the adenosine triphosphate-binding cassette
      transporter 1 gene on plasma lipids and carotid atherosclerosis.
AB  - Variants in the adenosine triphosphate-binding-cassette transporter 1 (ABCA1)
      gene are known to affect high-density lipoprotein cholesterol and plasma
      triglycerides and the development of atherosclerosis. We investigated the
      influence of the R219K and I883M variants in the ABCA1 gene on plasma lipids and
      carotid intima media thickness and plaque extent in 688 healthy men (40-60 years
      old). The R219K variant showed no effect on plasma lipids, but carriers of the K
      allele displayed a lower intima media thickness (P = .001) and a reduced risk of
      advanced plaque extent (odds ratio [OR], 0.59; 0.39-0.88; P = .009) compared with
      noncarriers. However, this risk reduction was observed in nonsmokers only (OR,
      0.47; 0.27-0.80; P < .001), but not in smokers (OR, 0.75; 0.41-1.39; P = .2). The
      I883M variant showed no effect on plasma lipids or carotid atherosclerosis. Risk
      of advanced plaque extent was reduced in subjects carrying the R219K variant
      alone (OR, 0.59; 0.38-0.94; P = .025), but not in subjects carrying both
      variants. Haplotype distribution did not differ between subjects with and without
      advanced atherosclerosis irrespective of smoking history. We conclude that
      smoking abrogates the protective effect of the R219K.

PMID- 18803946
TI  - Hormonal regulation of intracellular lipolysis in C57BL/6J mice: effect of diet
      induced adiposity and data normalization.
AB  - The breakdown of intracellular triglycerides in adipose tissue provides fatty
      acids and glycerol as substrates for oxidation. However, the exposure of target
      organs to excess free fatty acids is associated with the development of insulin
      resistance and impaired regulation of carbohydrate metabolism, suggesting that
      the control of triglyceride breakdown is an important factor in balancing health
      and disease. We have studied the temporal influence of diet-induced changes in
      adiposity on the response of intracellular lipolysis to epinephrine +/- insulin
      using freshly isolated adipocytes from C57BL/6J mice fed a low-fat (10% kcal) or
      high-fat (HF, 45% kcal) diet for 1, 4, or 12 weeks. In this model, we also tested
      how data normalization affects the interpretation. The contribution of the
      epididymal fat to total body mass increased by approximately 15%, 45%, and 100%
      after 1, 4, and 12 weeks of HF diet consumption, respectively. In addition, HF
      feeding led to an increase in fasting insulin, that is, approximately 2-fold
      greater in HF- vs low-fat-fed mice at 4 and 12 weeks. We found that diet-induced
      changes in adiposity did not alter the lipolytic response to epinephrine when
      data were normalized per DNA (ie, per cell); however, the lipolytic potential of
      the organ (ie, the lipolytic rate per cell multiplied by the total number of
      cells) was increased in isolated adipocytes after 4 and 12 weeks of HF feeding.
      We also observed a marked impairment in insulin-mediated inhibition of
      epinephrine-stimulated lipolysis after 4 and 12 weeks of HF feeding,
      demonstrating that diet-induced adiposity leads to insulin resistance in
      adipocytes. In conclusion, HF feeding in mice leads to greater rates of lipolysis
      via (1) an increase in the number of fat cells and (2) a defect in insulin
      signaling in adipocytes. The combination of these 2 alterations on the control of
      intracellular lipolysis suggests a mechanism(s) that (partly) explains how target
      organs could be exposed to excess lipid-derived energy substrates, for example,
      free fatty acids and glycerol.

PMID- 18803947
TI  - Adipokines influencing metabolic and cardiovascular disease are differentially
      regulated in maintenance hemodialysis.
AB  - Adipokines including leptin, adiponectin, visfatin, resistin, and interleukin
      (IL)-6 significantly influence energy metabolism, insulin sensitivity, and
      cardiovascular health. In the current study, we investigated serum levels of
      these adipokines in diabetic and nondiabetic patients on maintenance hemodialysis
      (MD) as compared with controls with a glomerular filtration rate greater than 50
      mL/min. Serum leptin, adiponectin, high-molecular-weight (HMW) adiponectin,
      visfatin, resistin, and IL-6 were determined by enzyme-linked immunosorbent assay
      in control (n = 60) and MD (n = 60) patients and correlated to clinical and
      biochemical measures of renal function, glucose, and lipid metabolism, as well as
      inflammation. Adiponectin, visfatin, resistin, and IL-6 were significantly
      elevated in MD patients as compared with controls. In multivariate analyses, sex
      and body mass index were independently correlated with serum leptin levels in
      both controls and MD patients. Furthermore, insulin resistance was independently
      and negatively associated with adiponectin and HMW adiponectin in both groups.
      Moreover, circulating resistin levels were independently correlated with serum
      visfatin concentrations in control and MD patients. However, various independent
      associations were only found in either controls or patients on MD. Thus, serum IL
      6 levels were strongly and independently associated with C reactive protein and
      resistin in MD patients but not control subjects. We show that levels of various
      adipokines are significantly increased in MD patients. Furthermore, regulation of
      adipokines in vivo strongly depends on renal function. Regulation of HMW
      adiponectin is similar as compared with total adiponectin in the patients
      studied.

PMID- 18803948
TI  - Increased sympathetic reactivity may predict insulin resistance: an 18-year
      follow-up study.
AB  - Insulin resistance and sympathetic activity are related by a positive feedback
      system. However, which precedes the other still remains unclear. The present
      study aimed to investigate the predictive role of sympathoadrenal activity in the
      development of insulin resistance in an 18-year follow-up study. We also examined
      whether reactivity to 2 different stress tests, a cold pressor test and a mental
      stress test, would differ in their predictive power. The 2 tests are supposed to
      represent different reactivity mechanisms: alpha- and beta-adrenergic responses,
      respectively. At entry, arterial plasma epinephrine and norepinephrine
      concentrations were measured in 99 healthy men (age, 19.3 +/- 0.4 years, mean +/-
      SD) during rest, a mental stress test, and a cold pressor test. Fasting plasma
      glucose concentration was measured at entry and at follow-up. Insulin resistance
      at follow-up was calculated using the homeostasis model assessment of insulin
      resistance (HOMA-IR). Eighty subjects (81%) were eligible for follow-up after
      18.0 +/- 0.9 years (mean +/- SD). The norepinephrine responses to cold pressor
      test at entry predicted plasma glucose concentration (r = 0.301, P = .010) and
      HOMA-IR (r = 0.383, P = .004) at follow-up in univariate analyses. In multiple
      regression analyses, corrected for fasting glucose at entry, family history of
      diabetes, blood pressure-lowering medication, body mass index at entry, and level
      of exercise, norepinephrine response to cold pressor test was found to be a
      positive predictor of future HOMA-IR (P = .010). This is the first long-term
      follow-up study in white subjects showing that sympathetic reactivity predicts
      future insulin resistance 18 years later. These findings may provide further
      insights into the pathophysiologic mechanisms of insulin resistance.

PMID- 18803949
TI  - Progression-related bias in the monitoring of kidney function in patients with
      diabetes and chronic kidney disease.
AB  - The Cockcroft and Gault (CG) and Modification of Diet in Renal Disease (MDRD)
      equations underestimate the glomerular filtration rate (GFR) decline in diabetes.
      Do this decline and the albumin excretion rate (AER) influence their validity? In
      161 diabetic patients, isotopically determined GFR (i-GFR) (51Cr-EDTA) was
      compared with estimated GFR (e-GFR) by the CG, MDRD, and the new Mayo Clinic
      Quadratic (MCQ) equations. We searched for a relation between the error in e-GFR
      and the AER. An influence of the AER outcome on the e-GFR decline was evaluated
      in 63 subjects followed up over 3 years. The MDRD and the MCQ were more precise
      and accurate than the CG, but they were biased. The error increased with AER for
      the CG (r = 0.25, P = .001) and the MDRD (r = 0.20, P = .009), but not for the
      MCQ. For the 63 patients followed up, the e-GFR declines by the 3 estimations
      were related to the initial AER, whereas no relation with arterial blood
      pressure, hemoglobin A(1C), hemoglobin, and blood lipids emerged. The MCQ
      declines were more pronounced: -10.5% +/- 8.9% in the macroalbuminuric group (P <
      .05 vs both microalbuminuric [-2.6% +/- 10.1%] and normoalbuminuric [-0.1% +/-
      6.6%] groups), and were related to the outcome of the AER (r = 0.33, P < .05). As
      chronic kidney disease progresses in diabetes, the declining GFR and rising AER
      influence the estimation of GFR by the CG and MDRD equations, underestimating the
      GFR decline and the benefit of reducing the AER. The less affected MCQ evidences
      a slower e-GFR decline with AER control.

PMID- 18803950
TI  - Renal and metabolic effects of tempol in obese ZSF1 rats--distinct role for
      superoxide and hydrogen peroxide in diabetic renal injury.
AB  - Oxidative stress, that is, overproduction of reactive oxygen species and reduced
      antioxidant system activity, is implicated in the pathogenesis of diabetic
      complications; and therefore, superoxide dismutase (SOD) mimetic tempol should be
      protective in diabetic kidney. However, the effects of tempol in metabolic
      syndrome-associated renal injury have not been thoroughly examined. In this
      study, we examined the effects of 9 weeks of treatment with tempol on metabolic
      status, renal oxidative stress, and kidney function and structure in obese,
      diabetic, hypertensive ZSF(1) rats and their nondiabetic, hypertensive, lean
      littermates. The obese rats had significantly reduced total SOD and catalase
      activity, increased peroxidase activity and lipid peroxidation, and higher level
      of protein oxidation in renal cortical tissue compared with their lean
      littermates. These changes were accompanied by renal injury (proteinuria; reduced
      excretory function; and markedly increased glomerular and interstitial
      inflammation, proliferation, and collagen IV synthesis). Tempol treatment
      slightly increased total SOD activity, significantly reduced lipid peroxidation
      and peroxidase activity, but had no effect on catalase and protein oxidation.
      Tempol had no effects on blood pressure, renal hemodynamics and excretory
      function, and proteinuria in obese rats, yet improved insulin sensitivity and
      reduced renal inflammatory, proliferative, and fibrotic changes. Because tempol
      possesses no catalase activity and, in diabetes, not only SOD but also catalase
      is inhibited, it is possible that the toxicity of hydrogen peroxide (H(2)O(2))
      remains unaltered under tempol treatment. This study suggests that superoxide and
      H(2)O(2) may have distinct roles in the pathogenesis of diabetic renal injury,
      with superoxide mainly being involved in inflammatory, proliferative, and
      fibrotic changes, and H(2)O(2) in glomerular hemodynamics and proteinuria.

PMID- 18803951
TI  - Inverse association between liver fat content and hepatic glucose uptake in
      patients with type 2 diabetes mellitus.
AB  - The objective of this research was to study (1) the mutual relationship between
      liver fat content (LFC) and hepatic glucose uptake (HGU) in patients with type 2
      diabetes mellitus and (2) the relationship between changes in LFC and HGU uptake
      induced by rosiglitazone in these patients. Liver fat was measured with proton
      magnetic resonance spectroscopy and insulin-stimulated HGU with [(18)F]-labeled 2
      fluoro-2-deoxyglucose positron emission tomography in 54 patients with type 2
      diabetes mellitus and 8 healthy subjects. Measurements were repeated in diabetic
      patients after a 16-week intervention period with rosiglitazone (n = 27) or
      placebo (n = 27). Patients with diabetes had lower HGU (24.5 +/- 14.2 vs 35.6 +/-
      9.7 micromol/[kg min], P < .01) and higher LFC (10.9% +/- 9.2% vs 2.5% +/- 1.4%,
      P < .001) compared with healthy subjects. Liver fat was inversely associated with
      HGU (r = -0.31, P < .05), but more strongly with whole-body insulin sensitivity
      and adiponectin levels. Rosiglitazone treatment reduced liver fat by 24.8% (P =
      .01 vs placebo) and increased HGU by 29.2% (P = .013 vs placebo). This decrease
      in LFC was best explained by the increment in suppression of nonesterified fatty
      acid levels during hyperinsulinemia (P < .001) and improved glycemic control (P =
      .034), but not by changes in HGU. A significant inverse relationship between LFC
      and HGU was observed, but changes were not related. This suggests that the
      beneficial effects of rosiglitazone on liver metabolism are indirect and can be
      partly explained by increased suppression of nonesterified fatty acid levels,
      leading to reduced liver fat.

PMID- 18803952
TI  - Skin autofluorescence, a marker for advanced glycation end product accumulation,
      is associated with arterial stiffness in patients with end-stage renal disease.
AB  - Elevated cardiovascular mortality has been shown to be associated with increased
      arterial stiffness. However, the contribution of tissue accumulation of advanced
      glycation end products (AGEs) to increased arterial stiffness is unclear. We
      examined whether skin autofluorescence, a recently developed marker of tissue
      accumulation of AGEs, is associated with arterial stiffness in 120 Japanese
      patients with end-stage renal disease (ESRD) and 110 age- and sex-matched control
      subjects. The ESRD patients had significantly higher pulse wave velocity (PWV), a
      noninvasive measure of arterial stiffness, and skin autofluorescence than the
      control subjects. Skin autofluorescence was significantly associated with age in
      the group of all subjects (R(s) = 0.255, Spearman rank correlation test) and that
      of control subjects (R(s) = 0.493), but not in the group of ESRD subjects (R(s) =
      0.046). The PWV was significantly and positively associated with skin
      autofluorescence in the group of all subjects (R(s) = 0.335), controls (R(s) =
      0.246), and ESRD subjects (R(s) = 0.205). Multiple regression analyses showed
      that, in the group of all subjects, association of skin autofluorescence with PWV
      was significant even after adjustment for other covariates including the presence
      of ESRD and age. Moreover, for ESRD subjects, a significant association between
      skin autofluorescence and PWV was found, independent of age. Our findings
      demonstrate the potential usefulness of skin autofluorescence in people of color
      and demonstrate clinically for the first time the potential involvement of tissue
      accumulation of AGEs in the pathophysiology of arterial stiffness.

PMID- 18803953
TI  - Total peptide YY is a correlate of postprandial energy expenditure but not of
      appetite or energy intake in healthy women.
AB  - Peptide YY (PYY) and ghrelin have been associated with the regulation of energy
      balance. The objectives of this study were to determine whether total ghrelin and
      PYY after a standardized meal predict appetite scores and ad libitum energy
      intake (EI) and to examine the relationship between total ghrelin and PYY and
      postprandial energy expenditure (PEE). Twenty-five premenopausal women (age, 50.4
      +/- 2.0 years; body mass index, 23.5 +/- 2.2 kg/m(2)) were studied. Total PYY,
      total ghrelin (enzyme-linked immunosorbent assay), EE (indirect calorimetry), and
      appetite scores (visual analogue scales) were measured fasting and every 30
      minute for 3 hours after the ingestion of a standardized breakfast. Ad libitum EI
      was measured at lunch with a buffet-type meal. Peptide YY increased (P < .001)
      and total ghrelin decreased (P < .001) after breakfast. Significant changes in EE
      (P < .001) and appetite scores (P < .001) were noted postprandially. Appetite
      scores were consistently associated with ad libitum EI at lunch (r = -0.51 to
      0.40, P < .05), whereas no association between EI and prelunch total ghrelin and
      PYY was observed. Finally, partial correlation analyses revealed that total PYY
      was a significant independent correlate of PEE at 60, 90, 120, and 150 minutes (r
      = 0.37-0.51, P </= .05). These findings provide evidence that appetite scores are
      better correlates of EI than are circulating levels of total PYY or ghrelin and
      that total PYY could be involved in the regulation of PEE.

PMID- 18803954
TI  - Interactions of the advanced glycation end product inhibitor pyridoxamine and the
      antioxidant alpha-lipoic acid on insulin resistance in the obese Zucker rat.
AB  - Oxidative stress and protein glycation can contribute to the development of
      insulin resistance and complications associated with type 2 diabetes mellitus.
      The antioxidant alpha-lipoic acid (ALA) reduces oxidative stress and the
      formation of advanced glycation end products (AGEs) and improves insulin
      sensitivity in skeletal muscle and liver. The AGE inhibitor pyridoxamine (PM)
      prevents irreversible protein glycation, thereby reducing various diabetic
      complications. The potential interactive effects of ALA and PM in the treatment
      of whole-body and skeletal muscle insulin resistance have not been investigated.
      Therefore, this study was designed to determine the effects of combined ALA and
      PM treatments on reducing muscle oxidative stress and ameliorating insulin
      resistance in prediabetic obese Zucker rats. Obese Zucker rats were assigned to
      either a control group or to a treatment group receiving daily injections of the
      R-(+)-enantiomer of ALA (R-ALA, 92 mg/kg) or PM (60 mg/kg), individually or in
      combination, for 6 weeks. The individual and combined treatments with R-ALA and
      PM were effective in significantly (P < .05) reducing plantaris muscle protein
      carbonyls (33%-40%) and urine-conjugated dienes (22%-38%), markers of oxidative
      stress. The R-ALA and PM in combination resulted in the largest reductions of
      fasting plasma glucose (23%), insulin (16%), and free fatty acids (24%) and of
      muscle triglycerides (45%) compared with alterations elicited by individual
      treatment with R-ALA or PM. Moreover, the combination of R-ALA and PM elicited
      the greatest enhancement of whole-body insulin sensitivity both in the fasted
      state and during an oral glucose tolerance test. Finally, combined R-ALA/PM
      treatments maintained the 44% enhancement of in vitro insulin-mediated glucose
      transport activity in soleus muscle of obese Zucker rats treated with R-ALA
      alone. Collectively, these results document a beneficial interaction of the
      antioxidant R-ALA and the AGE inhibitor PM in the treatment of whole-body and
      skeletal muscle insulin resistance in obese Zucker rats.

PMID- 18803955
TI  - Effects of telmisartan on adiponectin levels and body weight in hypertensive
      patients with glucose intolerance.
AB  - Few studies have analyzed intraclass differences in angiotensin II receptor
      blockers (ARBs) with respect to antidiabetic or metabolic effects. We designed a
      prospective randomized study to compare a peroxisome proliferator-activated
      receptor-gamma (PPARgamma)-activating ARB with a nonactivating ARB to delineate
      the effects on metabolic factors associated with cardiovascular disease. Subjects
      initially comprised 153 hypertensive patients (72 men, 81 women; mean age, 67.9
      +/- 7.8 years) with diagnosed glucose intolerance on the glucose loading test.
      Patients were randomly assigned to receive 6-month administration of telmisartan
      47.0 mg/d (TEL) or candesartan 8.4 mg/d (CAN), or to have no change in drug
      regimen (control group, CTL). Fasting plasma glucose level was significantly
      reduced in TEL (n = 46) compared with CTL (n = 47) (percentage of change from
      baseline, -1.7% vs +2.2%; P = .045). Percentage of increase in adiponectin was
      significantly larger in TEL than in CTL (+10.5% vs +2.2%, P = .025), but not
      significantly larger in CAN (n = 44) than in CTL (+4.9% vs +2.2%; P = .13).
      Percentage of decrease in body weight from baseline was significantly enhanced in
      TEL compared with CTL (-2.2% vs -0.8%, P = .023) and CAN (-2.2% vs -0.3%, P =
      .007). Telmisartan decreased body weight while increasing serum adiponectin
      levels in hypertensive patients with glucose intolerance. Candesartan did not
      achieve similar improvements in these patients. Among ARBs, telmisartan may have
      a larger impact on obesity-related diseases that can lead to cardiovascular
      disorders.

PMID- 18803956
TI  - Reproducibility of postprandial lipemia tests and validity of an abbreviated 4
      hour test.
AB  - Postprandial lipemia test (PPLT) results are predictive of cardiovascular disease
      risk. However, their reproducibility must be established before they can be
      clinically useful. Therefore, we investigated PPLT reproducibility by testing 9
      men and women (body mass index, 20-41 kg/m(2); age, 21-40 years) on 4 separate
      occasions (n = 36 PPLTs total) separated by 1 week. Furthermore, because PPLTs
      are time consuming, we assessed the validity of an abbreviated PPLT. During the
      PPLT, venous blood was obtained before and every hour for 8 hours after a high
      fat meal, which consisted of ice cream and heavy cream (approximately 800 kcal,
      71% fat calories). Total and triglyceride-rich lipoprotein (TRL) triglyceride
      concentrations were measured in plasma. Total area under the curve (AUC) for
      total triglycerides was highly reproducible (within-subject coefficient of
      variation, 8%; intraclass correlation coefficient, 0.82); however,
      reproducibility was low for total triglyceride incremental AUC and both total and
      incremental TRL triglyceride AUCs (within-subject coefficients of variation, 20%
      31%; intraclass correlation coefficients, 0.28-0.54). Four-hour lipemic responses
      were highly predictive of 8-hour responses (R(2) = 0.89-0.96, P <or= .0001). In
      conclusion, PPLTs are highly reproducible when lipemic responses are determined
      as the total AUC for total triglycerides. However, large variability in
      incremental AUC and TRL triglyceride responses may preclude their clinical
      utility. Furthermore, abbreviated 4-hour PPLTs are a valid surrogate for longer
      tests and may make PPLTs more feasible in a clinical setting.

PMID- 18803957
TI  - Early life development and health: impact on later life--introduction.

PMID- 18803958
TI  - Understanding the potency of stressful early life experiences on brain and body
      function.
AB  - Early life experiences have powerful effects on the brain and body lasting
      throughout the entire life span and influencing brain function, behavior, and the
      risk for a number of systemic and mental disorders. Animal models of early life
      adversity are providing mechanistic insights, including glimpses into the
      fascinating world that is now called "epigenetics" as well as the role of
      naturally occurring alleles of a number of genes. These studies also provide
      insights into the adaptive value as well as the negative consequences, of early
      life stress, exposure to novelty, and poor-quality vs good-quality maternal care.
      Animal models begin to provide a mechanistic basis for understanding how brain
      development and physiological functioning is affected in children exposed to
      early life abuse and neglect, where there is a burgeoning literature on the
      consequences for physical health and emotional and cognitive development. An
      important goal is to identify interventions that are likely to be most effective
      in early life and some guidelines are provided.

PMID- 18803959
TI  - Prenatal exposure to sex steroid hormones and behavioral/cognitive outcomes.
AB  - Experimental studies in animals indicate that androgen exposure in fetal or
      neonatal life largely accounts for known sex differences in brain structure and
      behavior. Clinical research in humans suggests similar influences of early
      androgen concentrations on some behaviors that show sex differences, including
      play behavior in childhood and sexual orientation in adulthood. Available
      research also suggests that sex steroid hormone exposure may contribute to sex
      differences in the risk of autism and affective disorders in schizophrenia.
      However, findings have been inconsistent for other characteristics that show sex
      differences, including aggression and spatial ability. Moreover, social and
      environmental factors may modulate some of the associations observed. This
      article reviews the evidence that early-life exposure to sex steroid hormones
      contributes to sexually dimorphic behavior and cognitive abilities in humans.

PMID- 18803960
TI  - Brain development: anatomy, connectivity, adaptive plasticity, and toxicity.
AB  - The developing brain is inherently more vulnerable to injury than the adult brain
      because brain development is extraordinarily complex, with periods of unique
      susceptibility. When brain developmental processes are suspended or delayed by
      any external influence, virtually no potential exists for subsequent regeneration
      and repair. This inevitably leads to long-lasting or permanent consequences.
      Recent genetic studies have contributed to a better understanding of the dynamic
      adaptive changes that occur in the developing brain as a consequence of genetic
      and environmental processes. Many industrial and environmental chemicals such as
      lead, methyl-mercury, polychlorinated biphenyls, arsenic, and toluene are
      recognized causes of neurodevelopmental disorders that lead to clinical or
      subclinical brain dysfunction. A number of these developmental disabilities arise
      from interactions between environmental factors and individual gene
      susceptibility. In addition, neurodevelopmental disorders of unknown origin, such
      as mental retardation, attention deficit disorder, cerebral palsy, and autism are
      becoming increasingly prevalent, with costly consequences for the family and
      society. The aim of this review is examine brain developmental anatomy,
      connectivity, adaptive plasticity, and toxicity in the context of current
      knowledge and future trends.

PMID- 18803961
TI  - Prenatal imprinting of postnatal specific appetites and feeding behavior.
AB  - Epigenetic influences on the fetus's genotype have been shown to occur during
      intrauterine life. Experimentally imposed extracellular dehydration in pregnant
      rats (a model for human hyponatremia caused by gravidic vomiting) brings about a
      dramatic enhancement of salt appetite not only in the dam, but also in offspring
      when they reach adulthood. This phenomenon has been verified in human newborn
      infants and adults whose mothers experienced nausea and/or vomiting during
      pregnancy. Alcohol consumption during pregnancy enhances its palatability for the
      offspring. Ingestion of olfactory test substances like anise or carrot by the
      mother during pregnancy gives rise to a preference for the same testants in the
      offspring. Under- or overnutrition in the pregnant mother appears to play a role
      in reprogramming the postnatal regulation of both feeding and fat reserves in
      offspring. Both maternal under- and overnutrition during pregnancy predispose the
      offspring to later development of obesity and type 2 diabetes mellitus. A careful
      examination of the systems concerned with the regulation of food intake, and the
      neurosubstances involved in such regulation, reveals some of the mechanisms by
      which maternal nutritional status can affect the offspring and their food-related
      behaviors.

PMID- 18803962
TI  - Impact of genetic and epigenetic factors from early life to later disease.
AB  - There is ample evidence that subtle changes in the early environment, not
      restricted to the fetal period but expanded to the plastic phase of early
      development, influence adulthood disease appearance. There is also evidence that
      genetic background resulting from our evolution is an important contributor to
      susceptibility to perinatal imprinting. However, rapid adjustment and
      optimization, at times necessary for survival, require a type of plasticity that
      the genome sequence alone cannot achieve. Without changing the genomic backbone,
      epigenetic modulation, in reaction to a given environment, results in functional
      adaptation of the genomic response. Evolutionally acquired genomic
      susceptibilities and environmentally induced epigenomic modulations occurring
      early in life impact on later development of human diseases.

PMID- 18803963
TI  - Low birth weight and blood pressure.
AB  - Evidence supporting the association of normal and pathologically elevated blood
      pressure with low birth weight is presented and discussed in this article because
      of the overwhelming global prevalence of hypertension and its impact on
      individuals and nations. The findings provide strong impetus for the medical and
      public health communities to consider the concept of the "developmental origins
      of health and disease" in developing approaches to address the growing burden of
      hypertension worldwide.

PMID- 18803964
TI  - Predisease biological markers: early diagnosis and prevention of arterial
      hypertension.
AB  - This review examines 2 potentially important morbid changes that may precede the
      onset of hypertension-capillary rarefaction (CR) and large artery rigidity (LAR).
      The mechanisms responsible for CR, currently measured in the skin
      microcirculation, as well those responsible for LAR, have yet to be fully
      delineated. Nor has the duration been determined of the latent period between the
      occurrence of these lesions and the onset of blood pressure elevation. It has
      been known for 2 decades that, because of the kidney's relatively rigid capsule,
      alterations in the abundant postglomerular microcirculation network (which can
      accommodate circa 80% of total renal blood flow) can lead to endothelial plasma
      leakage. Even a small amount of plasma leakage can increase interstitial pressure
      and lead to capillary collapse and CR. Simultaneously, or at a later time, these
      alterations could have an impact on the reflection wave profile in the thoracic
      aorta and, via abnormal endothelial proliferation and other vascular effects,
      give rise to LAR. Nonpharmacologic and/or pharmacologic interventions have been
      shown to exert positive effects on CR and/or LAR. Recent studies have
      demonstrated the beneficial actions of a bradykinin B2-receptor antagonist
      (HOE140) in the spontaneously hypertensive rat, the classic rat model for
      essential hypertension. The fact that CR and LAR both precede blood pressure
      elevation could serve as a basis for designing strategies to prevent hypertension
      from occurring. Because modern tools capable of measuring CR and LAR
      noninvasively have been developed, it should soon be feasible to identify these 2
      prehypertension markers in individual patients.

PMID- 18803965
TI  - Autism, a brain developmental disorder: some new pathopysiologic and genetics
      findings.
AB  - Autism is a severe neurodevelopmental disorder that is typically diagnosed by 3
      years of age. Core symptoms of autism include profound deficits in social
      interaction and communication, restricted interests, stereotyped responses, and
      other repetitive patterns of behavior. Other abnormalities include mental
      retardation and comorbid epilepsy. These symptoms underscore the consequences of
      genetic inheritance for brain function and behavior. The etiology of autism may
      involve an interaction between genetic susceptibility (mediated by multiple
      genes) and environmental factors influencing brain development.

PMID- 18803966
TI  - Do early-life insults contribute to the late-life development of Parkinson and
      Alzheimer diseases?
AB  - How early-life events "set the stage" for adult disease has emerged as a research
      focus. Historically, the epidemiology of disease risk factors has centered on
      adult life, with little scrutiny of early-life events. Here we review the concept
      that events in early life may contribute to late-life neurodegenerative disease
      development, with a focus on Parkinson disease (PD) and Alzheimer disease (AD).
      Suspect events in early life include infections, stress, poor nutrition, and
      environmental factors such as chemical and pesticide exposure. Adiposity appears
      to contribute to both PD and AD; and because early-life events contribute to the
      development of obesity, linkages may exist between early determinants of obesity
      and the subsequent development of these neurologic diseases. Many now suggest a
      life-course approach for determining the relative contributions of genetic and
      environmental factors in any chronic disease. This requires determining when
      during the life course that a given exposure has its greatest effect and how
      exposures may accumulate over the life span. The data for PD and AD suggest that
      a number of insults occurring early in life may lead or contribute to these
      diseases. More definitive knowledge of the key risk factors involved will be
      needed to implement intervention and preventative strategies early in life to
      dampen or prevent any adverse late-life outcomes.

PMID- 18803967
TI  - Parkinson disease: primacy of age as a risk factor for mitochondrial dysfunction.
AB  - In 1983, it was reported that certain drug users with a history of exposure to 1
      methyl-4-phenyl-1,2,3,6-tetrahydropyridine, a contaminant of an illicitly
      produced meperidine analogue, developed an irreversible syndrome resembling
      idiopathic Parkinson disease (PD). Soon thereafter, 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine's active metabolite, 1-methyl-4-phenylpyridine, was shown to
      be a complex I inhibitor. Activity of complex I (the point of entry for most
      electrons that traverse the mitochondrial electron transport chain) has been
      found to be impaired in the substantia nigra pars compacta and also in other
      brain tissues in PD patients. In 2006, high temporal and spatial resolution
      phosphorous functional magnetic resonance spectroscopy was used to demonstrate
      that, in 20 PD patients, mitochondrial dysfunction extended to the visual cortex.
      Epidemiologic studies have implicated a number of apparently disparate exogenous
      factors in the causation of PD. For example, exposure to certain pesticides and
      herbicides (many known to inhibit electron transport chain activity) increases PD
      risk. Parkinson disease risk can be doubled, tripled, or more in individuals with
      repeated head injuries. Over time, PD risk is almost doubled in men and women
      with prior type 2 diabetes mellitus. Nevertheless, despite evidence that certain
      exogenous and/or developmental factors play a role in causation of PD, their
      potential effect on PD incidence is greatly overshadowed by that of advancing
      age. In 1 prospective study, PD incidence rate in subjects at least 85 years old
      was about 14 times that observed in subjects aged 56 to 65 years. The dramatic
      effect of aging on PD risk may be explained in part by the fact that
      mitochondrial DNA deletions are abundant and cause functional impairment in aged
      human substantia nigra pars compacta neurons. High levels of these mutations are
      associated with electron transport chain deficiency, a situation that favors
      increased oxidative damage, Lewy body formation, and apoptotic cell death.
      Systematic study of the effects of putative risk factors in animal models of
      parkinsonism may be expected to improve our understanding of PD's complex
      pathogenesis.

PMID- 18803969
TI  - Preface: shoulder trauma.

PMID- 18803968
TI  - Synapse formation and cognitive brain development: effect of docosahexaenoic acid
      and other dietary constituents.
AB  - The brain is unusual among organs in that the rates of many of its characteristic
      enzymatic reactions are controlled by the local concentrations of their
      substrates, which also happen to be nutrients that cross the blood-brain barrier.
      Thus, for example, brain levels of tryptophan, tyrosine, or choline can control
      the rates at which neurons synthesize serotonin, dopamine, or acetylcholine,
      respectively. The rates at which brain cells produce membrane phospholipids such
      as phosphatidylcholine (PC) are also under such control, both in adult animals
      and, especially, during early development. If pregnant rats are fed the 3 dietary
      constituents needed for PC synthesis- docosahexaenoic acid, uridine, and choline
      starting 10 days before parturition and continuing for 20 days during nursing,
      brain levels of PC, and of the other membrane phosphatides (per cell or per mg
      protein), are increased by 50% or more. In adult animals, this treatment is also
      known to increase synaptic proteins (eg, synapsin-l, syntaxin-3, GluR-l, PSD-95)
      but not ubiquitous proteins like beta-tubulin and to increase (by 30% or more)
      the number of dendritic spines on hippocampal neurons. Docosahexaenoic acid
      currently is widely used, in human infants, to diminish the negative effects of
      prematurity on cognitive development. Moreover, docosahexaenoic acid, uridine (as
      uridine monophosphate), and choline are all found in mother's milk, and included
      in most infant formulas. It is proposed that these substances are part of a
      regulatory mechanism through which plasma composition influences brain
      development.

PMID- 18803970
TI  - Classification and imaging of proximal humerus fractures.
AB  - The decision to operate and the selection of the appropriate surgical modality
      for proximal humerus fractures are largely based on the fracture pattern.
      Understanding the particular fracture pattern in each case is complicated. Most
      well-accepted classification systems were developed based on radiographs
      complemented by intraoperative findings. Three-dimensional reconstructions based
      on CT currently available in most institutions allow a much better understanding
      of complex fractures. Modern thinking about fracture classification probably
      should be revisited in the light of improved imaging techniques.

PMID- 18803971
TI  - Percutaneous fixation of proximal humerus fractures.
AB  - Closed reduction and percutaneous fixation is a viable treatment option for
      displaced two-part, three-part, and valgus-impacted four-part proximal humerus
      fractures. Despite biomechanical studies demonstrating inferior stability
      compared with plate and intramedullary nail constructs, percutaneous fixation
      offers a minimally invasive approach with potential clinical advantages.
      Decreased scarring, improved cosmesis, and lower rates of avascular necrosis have
      been reported. Potential complications include pin migration, infection,
      avascular necrosis, neurovascular injury, and malunion. Clinical outcomes have
      been comparable with conventional techniques, with studies reporting
      approximately 70% good to excellent results.

PMID- 18803972
TI  - Locked intramedullary nailing for treatment of displaced proximal humerus
      fractures.
AB  - Controversy surrounds the optimal technique for fixation of displaced fractures,
      although locked intramedullary nailing is emerging as a preferred technique in
      managing displaced proximal humerus fractures in appropriately selected patients.
      This technique provides stable fracture fixation allowing early postoperative
      mobilization critical in ensuring a pain-free shoulder with a functional range of
      motion. Additional advantages include the ability to insert by way of a minimally
      invasive approach with limited soft tissue dissection, achieve accurate anatomic
      reduction, provide a secure construct even in the situation of osteopenic bone or
      comminution, and manage fractures of the proximal humerus extending into the
      shaft.

PMID- 18803973
TI  - Open reduction and internal fixation of proximal humerus fractures.
AB  - Open reduction of proximal humeral fractures has the advantage of providing
      direct control over each fracture fragment and permitting anatomic reduction and
      fixation with advanced devices. Modern fixed-angle locking plates designed
      specifically for proximal humerus fractures have allowed the expansion of
      surgical indications permitting surgeons to address more complicated fractures.
      Advanced preoperative imaging and fluoroscopy allow a better understanding of
      fracture patterns and permit the surgeon to use this knowledge intraoperatively.
      Research is required to further validate fracture classification systems, to
      develop surgical guidelines for decision making, and to compare the outcomes of
      the various treatments options for proximal humerus fractures.

PMID- 18803974
TI  - Hemiarthroplasty for proximal humeral fracture: restoration of the Gothic arch.
AB  - Proximal humerus fractures are the most common fractures of the shoulder girdle,
      and initial management of these injuries often determines final outcome. When
      arthroplasty is used to manage proximal humeral fractures, surgery remains
      technically demanding, and outcomes have been unpredictable. Recent advances in
      both technique and prosthetic implants have led to more successful and
      reproducible results. Key technical points include restoration of the Gothic
      arch, anatomic tuberosity reconstruction, and minimal soft tissue dissection.

PMID- 18803975
TI  - Reverse total shoulder arthroplasty for acute fractures and failed management
      after proximal humeral fractures.
AB  - Reverse shoulder arthroplasty (RSA) has a successful clinical record when used
      for treatment of arthropathy accompanied by rotator cuff insufficiency. Efforts
      to use the same technology for other conditions involving insufficient cuff
      function are related to proximal humeral fracture described in this review for
      which RSA has shown promise are treatment of failed hemiarthroplasty for
      treatment of proximal humeral fractures and treatment of complex fracture
      sequelae. Specific conclusions as yet are difficult to reach. Future studies are
      needed to determine if supplemental soft tissue procedures or modification of
      implant design will serve to improve functional outcome in this difficult-to
      treat subset of patients.

PMID- 18803976
TI  - Scapula fractures.
AB  - Fractures of the scapula are rare and the diagnosis and treatment may be
      unfamiliar to some surgeons. This article outlines a diagnostic work-up and
      treatment approach for the various types of scapular fractures. The approach
      helps guide decision making on operative versus nonoperative treatment based on
      what is known regarding prognosis and outcomes of management. Operative technique
      and fixation strategies are discussed for the common fracture patterns along with
      guidelines for postsurgical shoulder rehabilitation.

PMID- 18803977
TI  - Management of proximal humeral nonunions and malunions.
AB  - Surgical treatment of proximal humeral nonunions and malunions are technically
      challenging. Osteosynthesis with bone grafting for the treatment of nonunions is
      indicated in young, active patients with adequate bone stock in the proximal
      fragment and preservation of the glenohumeral articular surfaces. Corrective
      osteotomy may be a reasonable option for proximal humeral malunions in young
      patients without evidence of degenerative joint disease. Arthroplasty for
      proximal humerus nonunions and malunions has a guarded outcome because of
      limitations in shoulder motion, but pain relief is more consistently improved
      upon.

PMID- 18803978
TI  - Neurovascular injuries in shoulder trauma.
AB  - Although the incidence of neurovascular injury following shoulder trauma is
      relatively uncommon, a missed diagnosis may have serious clinical ramifications
      for the patient, and potential medical and legal implications for the treating
      surgeon. When treating these injuries with closed reduction or surgery the neural
      and vascular structures are at risk, and therefore a detailed and thorough
      baseline neurovascular status is essential before treatment. We suggest a
      systematic clinical approach when presented with trauma to the shoulder. This
      article provides an easily reproducible yet comprehensive approach to the
      diagnosis, identification, and treatment of neurovascular injuries following
      shoulder trauma.

PMID- 18803979
TI  - Management of acute clavicle fractures.
AB  - It has been believed since the time of Hippocrates that clavicle fractures
      require little more than benign neglect by clinicians. Although many patients who
      have clavicle injuries do achieve adequate healing and functional recovery
      without surgical interventions, good outcomes, especially with displaced
      fractures, are not universal. Recent literature suggests that a subset of
      midclavicular injuries may warrant primary surgical treatment to minimize the
      incidence of nonunion and/or symptomatic malunion. Furthermore, certain types of
      clavicular injuries result in suboptimal outcomes when managed nonoperatively.
      This article is based on the currently available clinical evidence on the
      evolving management of acute clavicle fractures.

PMID- 18803980
TI  - Anterior glenohumeral joint dislocations.
AB  - The glenohumeral joint is the most mobile articulation in the body and the most
      commonly dislocated diarthroidal joint. Anterior dislocation is by far the most
      common direction and can lead to instability of the glenohumeral joint, which
      ranges from subtle increased laxity to recurrent dislocation. Overtime,
      understanding of anterior shoulder dislocations and the resulting instability has
      improved. Likewise, significant advances in arthroscopic equipment have allowed
      use of the arthroscope to address anatomically the various lesions that cause
      instability. This article reviews the anatomy, pathophysiology, clinical
      evaluation, and treatment of anterior shoulder instability.

PMID- 18803981
TI  - Traumatic posterior glenohumeral dislocation: classification, pathoanatomy,
      diagnosis, and treatment.
AB  - Posterior humeral dislocations often go undetected. Proposed explanations for the
      delay in diagnosis include failure of the evaluating physician to include the
      condition in the differential diagnosis, suboptimal radiographic evaluation and
      interpretation, and coincidental injuries such as fractures that can confound the
      patient's presentation. It is imperative that the orthopedic surgeon develop a
      complete understanding of the nature of this injury and its treatment so that
      patients who present with this condition can be diagnosed and treated
      effectively. This article provides a detailed discussion of the classification,
      pathoanatomy, diagnosis, and treatment of traumatic posterior glenohumeral
      dislocation.

PMID- 18803982
TI  - Acromioclavicular and sternoclavicular joint injuries.
AB  - Acromioclavicular (AC) joint injuries are a frequent diagnosis following an acute
      shoulder injury. The literature on AC joint dislocation is extensive, reflecting
      the intense debate surrounding the topic. The choice of treatment is influenced
      by factors including the type of injury, the patient's occupation, the patient's
      past medical history, the acuity of the injury, and patient expectations.
      Sternoclavicular (SC) joint dislocation is an uncommon injury. The treatment of
      acute anterior SC joint dislocations is controversial. It is difficult to study
      with a well-designed prospective study because of the low frequency of this
      injury. Posterior dislocations are much less common than anterior dislocations.
      Posterior dislocations, however, are more serious; they are associated with
      significant complications and require prompt attention.

PMID- 18803983
TI  - Drug interactions between chemotherapeutic regimens and antiepileptics.
AB  - BACKGROUND: Drug-drug interactions (DDIs) are commonly seen in daily clinical
      practice, particularly in the treatment of patients with cancer. Seizures are
      often seen in patients with brain tumors and brain metastases, in whom
      antiepileptic drugs (AEDs) are often indicated. The risk for DDIs between
      anticancer drugs and AEDs is high. OBJECTIVE: This review aimed to investigate
      the types of interactions that are observed between the AEDs and the most
      commonly prescribed chemotherapeutic regimens. The risk for DDIs is discussed
      with regard to tumor type. METHODS: Data on DDIs between anticancer drugs and
      AEDs were compiled from the British National Formulary, Drug Information
      Handbook, and Micromedex Healthcare Series version 5.1. Product information of
      the individual drugs, as well as literature on anticancer drug-AED interactions,
      was searched using PubMed (years: December 1970 to January 2008; search terms:
      anticancer, antiepileptic, chemotherapy regimen, drug interactions, and the
      generic names of the individual anticancer drugs and AEDs [acetazolamide,
      carbamazepine, ethosuximide, felbamate, gabapentin, lamotrigine, levetiracetam,
      oxcarbazepine, phenobarbital, phenytoin, primidone, tiagabine, topiramate,
      valproic acid, vigabatrin, and zonisamide]). RESULTS: Our search identified
      clinically important DDIs observed with single-agent and combination regimens
      used for the treatment of breast cancers, colorectal cancers, lung cancers,
      lymphomas, and renal cell carcinomas. Carbamazepine, phenytoin, phenobarbital,
      and primidone were found to have prominent cytochrome P450 (CYP) enzyme-induction
      effects, while valproic acid had an inhibitory effect. The isozymes of major
      relevance to anticancer drug-AED interactions included CYP3A4, CYP2C9, and
      CYP2C19. Induction or inhibition of these isozymes by AEDs can cause a decrease
      or increase in anticancer drug concentrations. Similarly, enzyme inhibition or
      induction by anticancer drugs can lead to toxicity or loss of seizure control.
      CONCLUSIONS: In this review of anticancer drug-AED DDIs, carbamazepine,
      phenytoin, phenobarbital, primidone, and valproic acid were found to interact the
      most frequently with anticancer drugs. Based on the results of this review,
      clinicians should be vigilant when AEDs are prescribed concurrently with
      anticancer drugs. DDIs can be avoided or minimized by selecting alternative AEDs
      that are less likely to interact. However, if potentially interacting drug
      combinations must be used for treatment, serum drug concentrations should be
      closely monitored to avoid toxicity in the patient, as well as to ensure adequate
      chemotherapeutic and antiepileptic coverage.

PMID- 18803984
TI  - Suggested insulin regimens for patients with type 1 diabetes mellitus who wish to
      fast during the month of Ramadan.
AB  - OBJECTIVES: This paper reviews available information on insulin regimens that may
      enable patients with type 1 diabetes mellitus to fast during the month of Ramadan
      with minimal complications. It also provides guidance for health care
      professionals in managing patients who wish to observe the fast. METHODS:
      Relevant English-language articles were identified through searches of the
      MEDLINE, EMBASE, and Index Medicus Eastern Mediterranean Region databases (all,
      1980-2008) conducted in February 2008 using the terms Ramadan, fasting, type 1
      diabetes mellitus, hypoglycemia, and hypotension. Only original research and
      review articles related to adult patients with type 1 diabetes were considered
      for review, excluding pregnant women and patients with poorly controlled disease.
      RESULTS: The literature review identified 5 clinical trials relevant to type 1
      diabetes and fasting. Two main meals are eaten during Ramadan, one before dawn
      (Suhur) and the other at sunset (Iftar). Suggested adjustments to the insulin
      regimen during fasting include using 70% of the pre-Ramadan dose, divided as
      follows: 60% as insulin glargine given in the evening and 40% as an ultra-short
      acting insulin (insulin aspart or lispro) given in 2 doses, 1 at Suhur and 1 at
      Iftar. Alternatively, 85% of the pre-Ramadan dose may be divided as 70%
      Ultralente and 30% regular insulin, both given in 2 doses, 1 at Suhur and 1 at
      Iftar. Another option is to give 100% of the pre-Ramadan morning dose of 70/330
      premixed insulin at Iftar and 50% of the usual evening dose at Suhur. Patients
      who observe the fast should be advised to monitor their blood glucose
      regularly,avoid skipping meals or overeating,and maintain contact with their
      physician throughout the fast. The fast should be broken immediately if blood
      glucose drops below 60 mg/dL (3.3 mmol/L). Breaking the fast should be considered
      when blood glucose drops below 80 mg/dL (4.4 mmol/L), and the fast should be
      interrupted if blood glucose rises above 300 mg/dL (16.7 mmol/L) to avoid
      diabetic ketoacidosis. Fasting is contraindicated in patients with poorly
      controlled type 1 diabetes,including those with a history of severe hypoglycemia
      and/ or diabetic ketoacidosis at least 3 months before Ramadan; those with
      comorbid conditions (eg, unstable angina, uncontrolled hypertension, advanced
      macrovascular complications, infections, renal insufficiency);; those who are
      noncompliant with diet and medication; those who engage in intense physical
      activity; pregnant women; and the elderly. CONCLUSION: Patients with type 1
      diabetes who wish to fast during Ramadan should follow specific recommendations
      and be closely monitored by their physician.

PMID- 18803985
TI  - Benefits and risks of adjunctive inhaled corticosteroids in chronic obstructive
      pulmonary disease: a meta-analysis.
AB  - BACKGROUND: Several clinical trials have evaluated the benefits associated with
      adding an inhaled corticosteroid (ICS) to a long-acting bronchodilator in the
      treatment of severe or very severe (stage III or IV) chronic obstructive
      pulmonary disease (COPD). OBJECTIVE: We conducted a meta-analysis to elucidate
      the benefits and risks associated with adjunctive ICS treatment in patients with
      severe or very severe COPD. METHODS: A systematic literature search of MEDLINE,
      EMBASE, and the Cochrane Collaboration's Central Register of Controlled Clinical
      Trials (from initiation through April 2008) was conducted by 2 investigators
      working independently. A search strategy using key medical subject headings and
      text key words was performed using the Cochrane Collaboration's Highly Sensitive
      Search Strategy for MEDLINE and the McMaster University Health Information
      Research Unit EMBASE search strategy. To be included in this meta-analysis,
      studies had to be randomized controlled trials; compare the use of ICS in
      combination with long-acting beta-agonists (LABAs) or tiotropium with long-acting
      bronchodilator monotherapy; include only subjects with COPD and forced expiratory
      volume in 1 second (FEV(1)) <80% and an FEV(1)/forced vital capacity ratio <70%;
      follow up patients for a minimum of 24 weeks; and report data on either mortality
      or exacerbations. We evaluated 3 efficacy end points (exacerbations, mortality,
      and change in St. George's Respiratory Questionnaire [SGRQ] score), 2
      tolerability end points (pneumonia and oral candidiasis), and study withdrawals.
      Rate ratios and relative risks (RRs) were calculated using a random effects
      model. Statistical heterogeneity was addressed using the Q statistic and I(2)
      value. The Egger weighted regression statistic and visual inspection of funnel
      plots were used to assess publication bias. RESULTS: A total of 9 studies met the
      inclusion criteria (N = 7,992 subjects). Seven trials provided exacerbation rates
      and 8 trials provided data on overall mortality. Change in SGRQ score from
      baseline was reported in 6 trials while pneumonia and oral candidiasis were
      reported in 5 and 6 studies, respectively. The incidence of patient withdrawal
      was reported in 8 studies. Exacerbations (rate ratio, 0.82; 95% CI, 0.72-0.92)
      and SGRQ score (weighted mean difference, -1.98 points; 95% CI, -2.56 to -1.40)
      were reduced with adjunctive ICS treatment but mortality was not affected (rate
      ratio, 0.86; 95% CI, 0.73-1.02). Both pneumonia (RR, 1.68; 95% CI, 1.28-2.21) and
      oral candidiasis (RR, 2.93; 95% CI, 1.94-4.42) were increased with adjuvant ICS
      treatment. Patient study withdrawal for any reason (RR, 0.83; 95% CI, 0.74- 0.93)
      was less likely with adjuvant ICS treatment. On visual inspection of the funnel
      plots, publication bias could not be ruled out for either efficacy or
      tolerability end point analysis. However, inspection of the Egger weighted
      regression statistic suggested the low likelihood of publication bias for all end
      points. CONCLUSIONS: Addition of an ICS to a LABA was associated with a reduced
      risk for exacerbations but an increased risk for pneumonia and oral candidiasis
      compared with long-acting bronchodilator monotherapy in this meta-analysis of 9
      randomized controlled trials. While measured patient-perceived health and well
      being increased to a statistically significant level, this did not translate into
      a clinically meaningful level for all patients with combination treatment. Lower
      risk of study withdrawal was observed in adjuvant ICS patients. The benefits and
      risks associated with adjunctive ICS treatment will need to be assessed when
      making decisions regarding its use.

PMID- 18803986
TI  - Lapatinib: a dual inhibitor of human epidermal growth factor receptor tyrosine
      kinases.
AB  - BACKGROUND: Lapatinib, the first dual inhibitor of epidermal growth factor
      receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) tyrosine
      kinases, was approved by the US Food and Drug Administration (FDA) in 2007. It is
      indicated for use in combination with capecitabine for the treatment of patients
      with advanced breast cancer or metastatic breast cancer (MBC) whose tumors
      overexpress HER2 (ErbB2) and who have received previous treatment that included
      an anthracycline, a taxane, and trastuzumab. OBJECTIVE: This review summarizes
      the pharmacology, pharmacokinetics, clinical efficacy, and safety profile of
      lapatinib, and its current and potential role in the treatment of breast cancer
      and other malignancies. METHODS: Relevant English-language publications were
      identified through searches of MEDLINE (1966-May 2008),the American Society of
      Clinical Oncology abstracts database (2000-2007), abstracts from the San Antonio
      Breast Cancer Symposium (2005-2007), and the FDA Web site (January 2008). Search
      terms included lapatinib, GW572016, HER2, EGFR, receptor tyrosine kinase, dual
      receptor blockade, adverse events, and clinical trials. RESULTS: The T(max) of
      lapatinib after oral administration is 3 to 4 hours. Dividing the dose or
      administering it with food, particularly a high-fat meal, increases the AUC >2
      fold. Lapatinib is metabolized primarily by the cytochrome P450 3A4 isozyme, with
      1 metabolite remaining active against EGFR but not HER2. Due to drug
      accumulation, the t(1/2) of lapatinib is 24 hours with continuous dosing. In a
      Phase III trial comparing lapatinib and capecitabine with capecitabine alone in
      women with HER2-positive, locally advanced breast cancer or MBC that had
      progressed after treatment with an anthracycline, a taxane, and trastuzumab, the
      combination of lapatinib and capecitabine was associated with a numeric
      improvement in response rate compared with capecitabine alone (22% vs 14%,
      respectively; P = NS) and a significant increase in time to progression (6.2 vs
      4.3 months; hazard ratio = 0.57; 95% CI, 0.43-0.77; P < 0.001). Lapatinib has
      been reported to have antitumor activity in Phase II trials when used as first
      line therapy for MBC, in patients with inflammatory breast cancer, and in
      patients with central nervous system metastases. Phase II trials in other solid
      tumor types found modest activity. The approved dosing of lapatinib is 1,250 mg
      PO QD given continuously in combination with capecitabine 2,000 mg/m(2) daily
      administered in 2 divided doses on days 1 to 14 of a 21-day cycle. The most
      common clinical toxicities of all grades associated with lapatinib used in
      combination with capecitabine in the pivotal clinical trial were diarrhea (65%),
      hand-foot syndrome (53%), nausea (44%), rash (29%), and fatigue (24%). Cardiac
      toxicity appears to be less frequent with lapatinib than with trastuzumab.
      CONCLUSIONS: Lapatinib is a dual inhibitor of the EGFR and HER2 tyrosine kinases.
      It is approved by the FDA for use in combination with capecitabine for the
      treatment of HER2-positive MBC that has progressed with standard treatment. In
      clinical trials, this combination was associated with a significant improvement
      in the time to progression in patients with MBC. Lapatinib's efficacy in other
      malignancies that overexpress EGFR and/or HER2 is under evaluation.

PMID- 18803987
TI  - Efficacy and tolerability of exenatide monotherapy over 24 weeks in antidiabetic
      drug-naive patients with type 2 diabetes: a randomized, double-blind, placebo
      controlled, parallel-group study.
AB  - BACKGROUND: Evaluation of exenatide monotherapy in patients with type 2 diabetes
      may be of clinical interest based on improvements in glycemic control and weight
      that have been reported with the use of exenatide in combination with oral
      antidiabetic agents. OBJECTIVE: The aim of this study was to evaluate the
      efficacy and tolerability of exenatide monotherapy in patients with type 2
      diabetes naive to antidiabetic agents and whose disease was inadequately
      controlled with diet and exercise alone. METHODS: This 24-week, double-blind,
      placebo-controlled, parallel-group study was conducted at 23 centers across the
      United States, Puerto Rico, Romania, Russia, and India. Patients aged >or=18
      years with type 2 diabetes were randomly assigned to receive exenatide 5 microg,
      exenatide 10 microg, or placebo administered SC BID. Patients were instructed by
      investigators to maintain their individualized prestudy diet and exercise
      regimens throughout the study. Efficacy measures included: glycosylated
      hemoglobin (HbA(1c)); fasting serum glucose (FSG); 6-point self-monitored blood
      glucose; percentages of patients achieving HbA(1c) values <or=6.5% and <or=7.0%;
      weight; and homeostasis model of beta-cell function (HOMA-B, a clinical measure
      of pancreatic beta-cell function). Tolerability measures included patient
      reported adverse events, hypoglycemia, and blood pressure. RESULTS: A total of
      232 patients were included in the intent-to-treat population (130 men, 102 women;
      68% white; mean [SD] age, 54 [10] years; duration of type 2 diabetes, 2 [3]
      years; weight, 86 [16] kg; body mass index, 31 [5] kg/m(2); HbA(1c), 7.8%
      [0.9%]). At end point, least-squares mean (SE) HbA(1c) reductions (%) from
      baseline were significantly greater with exenatide 5 and 10 microg than placebo (
      0.7 [0.1] and -0.9 [0.1] vs -0.2 [0.1]; P = 0.003 and P < 0.001, respectively),
      as were FSG reductions (mg/dL) (-17.5 [4.0] and -18.7 [4.0] vs -5.2 [4.0]; P =
      0.029 and P = 0.016, respectively). Changes in daily mean postprandial glucose
      excursions (mg/dL) from baseline to end point were significantly greater with
      exenatide 5 and 10 microg than placebo (-21.3 [2.7] and -24.7 [2.7] vs -8.3
      [2.5]; both, P < 0.001). With exenatide 5 and 10 microg, 31% and 35% of patients
      achieved HbA(1c) <or=6.5% at end point versus 19% with placebo (P = NS and P =
      0.026, respectively), while 48% and 46% versus 29% achieved HbA(1c) <or=7.0% (P =
      0.024 and P = 0.036, respectively). Changes in weight (kg) at 24 weeks were
      greater with exenatide 5 and 10 (2)g than placebo (-2.8 [0.3] and -3.1 [0.3] vs 
      1.4 [0.3]; P = 0.004 and P < 0.001, respectively). HOMA-B values increased from
      baseline to end point by 32% and 28% in the exenatide 5- and 10-microg groups,
      respectively, versus 6% for placebo. Improvements from baseline to end point in
      HOMA-B were significantly greater with exenatide 5 and 10 microg than placebo (P
      = 0.002 and P = 0.010, respectively). Significant improvements in mean systolic
      and diastolic blood pressure (mm Hg) from baseline to end point were also
      observed with exenatide (systolic, both 5 and 10 microg, -3.7 [1.2] [P = 0.037];
      diastolic, 10 microg, -2.3 [0.7] [P = 0.046]) versus placebo (systolic, -0.3
      [1.2]; diastolic, -0.3 [0.7]). Overall, 25% of patients reported >or=1 treatment
      emergent adverse event. Nausea was reported with the greatest incidence (5
      microg, 3%; 10 microg, 13%; placebo, 0%; P = 0.010 for the combined exenatide
      group vs placebo). Most (88%) treatment-emergent adverse events were mild or
      moderate in intensity. Hypoglycemia was reported in 5%, 4%, and 1% of patients in
      the exenatide 5- and 10-microg and placebo groups, respectively (P = NS), with no
      incidents of severe hypoglycemia reported. CONCLUSIONS: In these patients with
      type 2 diabetes naive to treatment with antidiabetic agents, exenatide
      monotherapy was associated with improved HbA(1c), improved fasting and
      postprandial glucose control, reduced weight, improved beta-cell function (HOMA
      B), and improved blood pressure, and was well tolerated. These results suggest
      that exenatide monotherapy may provide a viable treatment option beyond diet and
      exercise and support further study of exenatide monotherapy in antidiabetic drug
      naive patients with type 2 diabetes.

PMID- 18803988
TI  - Effect of nicotine lozenges on affective smoking withdrawal symptoms: secondary
      analysis of a randomized, double-blind, placebo-controlled clinical trial.
AB  - BACKGROUND: The suggested mechanism for the effects of nicotine replacement
      medications such as nicotine lozenges on smoking abstinence is reduction in the
      withdrawal symptoms of emotional distress and craving (the subjective desire to
      smoke). OBJECTIVES: This study assessed the effect of nicotine lozenges on
      affective withdrawal symptoms (collectively termed emotional distress) and
      craving over 6 weeks of treatment and the role of emotional distress and craving
      in mediating the effect of the lozenges on smoking abstinence. METHODS: This was
      a secondary analysis of data from a randomized, double-blind, placebo-controlled
      clinical trial of nicotine lozenges. High-dependence smokers (those who smoked
      their first cigarette of the day within 30 minutes of waking) were assigned to
      receive the 4-mg lozenge; low-dependence smokers (those who smoked their first
      cigarette of the day >30 minutes after waking) were assigned to receive the 2-mg
      lozenge. Participants were randomized to receive active or placebo lozenges
      within these dose and dependence strata. Smokers were to rate their withdrawal
      symptoms daily during the baseline week (while still smoking) and for 6 weeks
      after starting treatment. Study analyses included the effect of the active
      lozenge on affective symptoms (ie, anxiety; anger, irritability, or frustration;
      difficulty concentrating; restlessness; and depressed mood) during weeks 1
      through 6 in high- and low-dependence smokers; the prospective associations
      between these symptoms and craving and subsequent abstinence; and the mediating
      influence of these symptoms on the lozenge's effect on abstinence. The analyses
      included smokers who provided symptom data for the baseline period and for at
      least week after the initiation of treatment. RESULTS: Of 1,818 smokers enrolled
      in the original study, this analysis included data from 1,144. The population was
      predominantly white, had a mean age ranging ranging from 40.65 to 46.01 years,
      and included slightly more women than men. The 2-mg lozenge did not have
      consistently significant effects on the withdrawal symptoms of emotional distress
      among low-dependence smokers; however, in high-dependence smokers, the 4-mg dose
      was associated with significant reductions versus placebo in overall emotional
      distress symptoms through week 4 (P < 0.001-P = 0.025), all individual symptoms
      through week 3 (P < 0.001-P = 0.035), and irritability and anxiety through week 4
      (P = 0.002-P = 0.049). In the low-dependence group, the 2-mg lozenge was
      associated with significant reductions versus placebo in craving through week 3
      (P = 0.012-P = 0.033), whereas in the high-dependence group, the 4-mg lozenge was
      associated with significant reductions in craving in each of the first 6 weeks (P
      < 0.001-P = 0.028). Among high-dependence smokers, both week-1 and week-2
      emotional distress scores were associated with a return to smoking by week 6 (P <
      0.001); among low dependence smokers, the association applied only to week-2
      symptoms (P = 0.017). Week-1 and week-2 craving was associated with a return to
      smoking at week 6 in both groups (P < 0.001-P = 0.001). Emotional distress
      modestly and inconsistently mediated the effects of the lozenges, accounting for
      3% to 13% of the treatment effects, whereas craving more strongly (though
      incompletely) mediated the treatment effects, particularly among high-dependence
      smokers, in whom it accounted for 29% to 39% of the treatment effects.
      CONCLUSIONS: In high-dependence smokers, the 4-mg nicotine lozenge significantly
      reduced all affective withdrawal symptoms through the first 4 weeks of treatment.
      Lozenge-related decreases in craving partially mediated the effect of treatment
      on abstinence, particularly in high-dependence smokers.

PMID- 18803989
TI  - Use of glargine in pregnant women with type 1 diabetes mellitus: a case-control
      study.
AB  - BACKGROUND: Insulin glargine is a once-daily basal insulin analog with prolonged
      duration of action and absence of an evident peak. Glargine is associated with
      reduced frequency of hypoglycemic episodes (mostly nocturnal) as well as
      effective glycemic control. Maintenance of good metabolic control before
      conception and throughout pregnancy is essential to lower the risk of fetal
      malformations. Glargine might be a valuable alternative in the management of
      pregnancies complicated by diabetes mellitus. However, because its clinical
      utility has not been established, the use of glargine is not currently
      recommended during pregnancy. OBJECTIVE: The aim of this study was to
      retrospectively evaluate (years 2004-2007) the effectiveness and safety of
      insulin glargine compared with neutral protamine Hagedorn (NPH) in women affected
      by type 1 diabetes mellitus (T1DM) during pregnancy. METHODS: The study comprised
      pregnant women affected by T1DM who were followed up in the Diabetes and
      Pregnancy Outpatient Clinic at the University of Palermo, Palermo, Italy, within
      8 +/- 3.4 weeks subsequent to a positive pregnancy test. All patients with T1DM
      were treated with conventional basal-bolus insulin therapy (aspart or lispro
      analogs at the 3 main meals plus glargine or NPH at bedtime). Healthy pregnant
      women were used as controls for fetal and neonatal parameters. Patients were
      consecutively enrolled. In all women, metabolic status was determined daily by
      mean glycemic values (2-hour postprandial blood glucose) and glycosylated
      hemoglobin (HbA1c) values (at 3-month intervals). Fetal measurements (<50th and
      >90th centiles of the head circumference, abdomen circumference, and femoral
      length) were evaluated by ultrasound at second and third trimesters. Weight and
      femoral length were assessed at birth, and neonates were classified according to
      the fetal growth curve for the Italian population (<10th centile = small for
      gestational age; and >90th centile = large for gestational age (LGA). RESULTS: A
      total of 73 pregnant women (30 with T1DM and 43 healthy [control]) were included
      in the study. Of the 30 diabetic pregnant women included in the study, 15 (mean
      [SD] age, 27.4 [5.2] years; mean pregravidic weight, 59.7 [11.7] kg) maintained
      their preconception therapy with glargine, and 15 (mean age, 30.1 [2.4] years;
      mean pregravidic weight, 60.7 [8.7] kg) with NPH. No significant difference was
      observed between the glargine-treated group and the NPH-treated group with regard
      to pregravidic hypertension, third-trimester preeclampsia, maternal complications
      and/or their progression during pregnancy (diabetic retinopathy, micro- or
      macroalbuminuria) and episodes of mild hypoglycemia, severe hypoglycemia, and
      ketosis. There were no significant between group differences in insulin
      requirements (IU/kg of body weight) and glycemic profile, with the exception of
      better fasting and 2 hours after breakfast glycemic values in the glargine group
      during the first (P = 0.008 and P < 0.001, respectively) and the second (P =
      0.015 and P = 0.016) trimesters, confirmed by the lower HbA1c levels in the first
      trimester (P = 0.037). The frequency of femoral length <50th centile at both
      second and third trimesters was 4/15 (26.7%) in the glargine-treated group (P =
      0.033 and P = 0.013, respectively, vs control), 3/15 (20.0%) and 1/15 (6.7%),
      respectively, in the NPH-treated group (both, P = NS vs control), and 2/43 (4.7%)
      and 1/43 (2.3%), respectively, in the control group. The prevalence of LGA was
      7/15 (46.7%) in the glargine group (P < 0.001 vs control), 4/15 (27.6%) in the
      NPH group (P = 0.033 vs control), and 2/43 (4.7%) in the control group.
      CONCLUSIONS: Although our retrospective study involved only a small number of
      participants, no significant difference was found in glycemic control between
      glargine and NPH treatments. Use of glargine was associated with a significantly
      higher frequency of femoral length <50th centile. Further larger prospective
      studies are necessary to assess the safety profile of glargine in T1DM during
      pregnancy.

PMID- 18803990
TI  - Massive bilateral pleural effusion associated with use of pioglitazone.
AB  - BACKGROUND: Pioglitazone is a peroxisome proliferator-activated receptor-gamma
      agonist that decreases insulin resistance in type 2 diabetes mellitus. However,
      it has been associated with fluid retention, peripheral edema, and congestive
      heart failure, which has become of particular concern. There are no reports in
      the literature of severe pleural effusions in a patient with normal cardiac
      function. CASE SUMMARY: A 54-year-old Asian woman weighing 77 kg developed
      massive bilateral pleural effusion after receiving pioglitazone (30 mg QD) in
      combination with glimepiride 2 mg BID and metformin 500 mg TID. Despite treatment
      with furosemide (20 mg intravenously at 12-hour intervals for 4 days) and a
      decrease in weight from 77 to 72 kg, the effusion persisted. However, it began to
      decrease after pioglitazone was discontinued, and it had resolved completely when
      the patient was evaluated on follow-up 1 month later in the outpatient
      department. CONCLUSIONS: This article reports a case of massive bilateral pleural
      effusion found in a patient with normal cardiac function who was receiving
      pioglitazone. After the drug was discontinued, the effusion resolved completely,
      indicating a probable adverse drug reaction.

PMID- 18803991
TI  - Efficacy and tolerability of salmeterol/fluticasone propionate versus montelukast
      in childhood asthma: A prospective, randomized, double-blind, double-dummy,
      parallel-group study.
AB  - BACKGROUND: Asthma control remains suboptimal in adults and children worldwide.
      Inhaled salmeterol/fluticasone propionate combination (SFC) and oral montelukast
      (MON) are 2 treatments available for childhood asthma. OBJECTIVE: This study, the
      PEdiatric Asthma Control Evaluation (PEACE), investigated the efficacy and
      tolerability of SFC compared with MON for the control of persistent asthma in
      children. METHODS: Children with asthma (forced expiratory volume in 1 second
      [FEV(1)] 55%-80% predicted; reversibility >or=12%) aged 6 to 14 years who were
      receiving only short-acting beta(2)-agonists entered a 2-week run-in period.
      Symptomatic patients (rescue use or symptoms during 4 of the last 7 days) were
      randomized to double-blind, double-dummy treatment with SFC 50/100 microg BID via
      multidose dry powder inhaler or MON 5-mg tablet QD for 12 weeks. The primary end
      point was change from baseline in morning peak expiratory flow (PEF). Efficacy
      assessments included lung function, asthma symptoms, rescue medication use, and
      asthma control. Tolerability was assessed by recording the number and type of
      adverse events (AEs) and the number of asthma exacerbations. RESULTS: Of 607
      patients screened, 548 were randomized to treatment. The SFC group contained 281
      patients and the MON group included 267. Demographic characteristics and baseline
      data were similar for both groups (mean age, 9.3 years for both groups; mean [SD]
      FEV(1), 1.49 [0.43] L in the SFC group and 1.48 [0.43] L in the MON group). There
      were more males in the MON group (179 [67%]) than in the SFC group (156 [56%]).
      The adjusted mean (SE) changes from baseline in morning PEF were 45.88 (2.82)
      L/min with SFC and 28.7 (2.86) L/min with MON (treatment difference, 17.16 L/min;
      95% CI, 9.23-25.08; P < 0.001). Compared with MON, the SFC group had
      significantly more asthma symptom-free days (odds ratio [OR], 1.74; 95% CI, 1.07
      2.82; P = 0.025), more rescue-free days (OR, 3.24; 95% CI, 2.09-5.02; P < 0.001),
      and more asthma-controlled weeks (difference in treatment medians over weeks 1
      12, 16.77%; 95% CI, 8.3-16.77; P < 0.001). Both treatments were well tolerated,
      with a similar number of patients reporting AEs (SFC group, 155/281 [55%]; MON
      group, 153/267 [57%]); the most common AE in both groups was headache (SFC group,
      66 [23%]; MON group, 72 [27%]). The mean exacerbation rates over 12 weeks (post
      hoc analysis) were 0.12 in the SFC group and 0.30 in the MON group (SFC/MON
      ratio, 0.40; 95% CI, 0.29-0.57; P < 0.001). CONCLUSIONS: In these children with
      uncontrolled asthma previously on short-acting beta(2)-agonist monotherapy (%
      predicted FEV(1) <80%, frequent asthma symptoms and rescue medication use),
      treatment with SFC was significantly more effective in improving morning PEF and
      other measures of asthma control and in decreasing exacerbation rates (in a post
      hoc analysis) than treatment with MON. The 2 drugs were both well tolerated, with
      similar numbers and types of AEs reported.

PMID- 18803993
TI  - Estimating the health benefits and costs associated with ezetimibe coadministered
      with statin therapy compared with higher dose statin monotherapy in patients with
      established cardiovascular disease: results of a Markov model for UK costs using
      data registries.
AB  - BACKGROUND: Ezetimibe has been reported to improve lipid control in patients with
      established cardiovascular disease (CVD). OBJECTIVE: The aim of this study was to
      estimate the potential long-term impact on health status of prescribing ezetimibe
      in combination with statin therapy in patients with established CVD and evaluate
      its cost-effectiveness in a health economic model. METHODS: A Markov model was
      used to compare ezetimibe and statin combination therapy with statin monotherapy.
      A published relationship linking changes in low-density lipoprotein cholesterol
      and cardiovascular events was used to estimate the cardiovascular events avoided
      through lipid-lowering therapies. The model was populated using results of
      extensive literature searches and a meta-analysis of clinical evidence. An
      adjustment was applied to model second-line lipid-lowering benefits. Conservative
      assumptions were used to extend the patient pathway beyond the clinical evidence.
      The analysis took the perspective of the UK Department of Health; therefore, only
      direct costs were included. Costs were calculated as year-2006 British pounds.
      RESULTS: For a cohort of 1,000 hypothetical male patients aged 55 years,
      ezetimibe coadministered with current statin therapy was estimated to prevent a
      mean of 43 nonfatal myocardial infarctions, 7 nonfatal strokes, and 26
      cardiovascular deaths over a lifetime, compared with doubling the current statin
      dose. The events avoided would provide a mean of 134 additional quality-adjusted
      life-years (QALYs). With a mean incremental cost of pound 3,693,000, the lifetime
      discounted cost per QALY gained would be pound 27,475 (95% CI, pound 27,331-
      pound 27,620) and would rise to pound 32,000 for men aged 75 years. CONCLUSIONS:
      The results suggest that, in some instances, ezetimibe coadministration may be
      cost-effective compared with statin monotherapy, but there are several
      limitations with this model. The economic effects of ezetimibe must be revisited
      when long-term effectiveness and safety data become available.

PMID- 18803994
TI  - Retrospective assessment of Medicaid step-therapy prior authorization policy for
      atypical antipsychotic medications.
AB  - BACKGROUND: Antipsychotic medications account for more prescription expenditures
      in Medicaid than any other therapeutic category. This has made them an attractive
      target for states hoping to curtail rising expenditures. OBJECTIVE: The objective
      of this study was to document the effects of a step-therapy prior authorization
      (PA) policy for atypical antipsychotic medications on: (1) Medicaid prescription
      expenditures among all Medicaid beneficiaries and (2) prescription and health
      service expenditures among patients with schizophrenia. METHODS: Prescription,
      inpatient, outpatient, and long-term care State Medicaid Research Files from
      Georgia and Mississippi from January 1, 1996, to December 31, 1997, were used to
      model an interrupted time-series analysis. We compared a step-therapy PA policy
      implemented in Georgia to a nonequivalent/no-treatment control group
      (Mississippi) over 10-month prepolicy, 11-month policy, and 3-month postpolicy
      periods. Segmented regression was used to estimate antipsychotic prescription
      expenditures among all eligible Medicaid beneficiaries. We used generalized
      estimating equations to model prescription and other health service expenditures
      with difference-indifference regressions among a cohort of patients with
      schizophrenia. RESULTS: Compared with Mississippi, Georgia saved approximately
      USD 7 million in atypical antipsychotic expenditures over the 11-month policy
      period. Among patients with schizophrenia, the PA policy was associated with a
      USD 19.62 per member per month (PMPM) decrease in atypical antipsychotic
      expenditures and a USD 2.20 PMPM increase in typical antipsychotic expenditures
      (both, P < 0.001). Among the same patients with schizophrenia however, the
      reduction in atypical antipsychotic expenditures was accompanied by a USD 31.59
      PMPM increase in expenditures for outpatient services (P < 0.001). CONCLUSION:
      Although PA of atypical antipsychotics was associated with significant
      prescription savings to the Georgia Medicaid program, among a vulnerable cohort
      of patients with schizophrenia, an increase in outpatient expenditures was
      associated with overall savings.

PMID- 18803995
TI  - Impact of corticosteroid-related symptoms in patients with immune
      thrombocytopenic purpura: results of a survey of 985 patients.
AB  - BACKGROUND: Corticosteroid (CS) therapy is effective in many patients with immune
      thrombocytopenic purpura (ITP), although it is associated with adverse effects.
      OBJECTIVE: This study was conducted to describe the CS-related symptom experience
      of adult patients with ITP and to compare the symptom experience of current users
      of CS, previous users of CS, and those who have never used CS. METHODS: In 2006,
      adult members of the Platelet Disorder Support Association (PDSA) who were listed
      in the organization's database, resided in the United States, and had a diagnosis
      of ITP were invited to participate in a Web-based survey. Symptom experience was
      assessed using 33 CS-related symptoms derived from a scale developed for use in
      patients undergoing organ transplantation. Symptom experience over the past 4
      weeks was measured in terms of the occurrence of symptoms (rated on a 5-point
      scale from 1 [never occurring] to 5 [always occurring]) and the distress
      associated with those symptoms (rated on a 5-point Likert scale from 0 [not at
      all distressing] to 4 [extremely distressing]). Respondents were categorized
      according to 4 patterns of CS use: current users, nonusers, previous users who
      stopped CS use <6 months earlier, and previous users who stopped CS use >or=6
      months earlier. RESULTS: The survey was completed by 985 patients with ITP (8.2%
      of the PDSA membership). The median age of the sample was 47 years, and the ratio
      of women to men was 3:1. One hundred sixteen patients (11.8%) were current CS
      users, 171 (17.4%) were nonusers, 99 (10.1%) had stopped CS use <6 months
      earlier, and 599 (60.8%) had stopped CS use >or=6 months earlier. In all 4
      groups, back pain, fatigue, sleep difficulties, muscle weakness, and difficulty
      seeing well were reported to be the most frequently occurring and most
      distressing symptoms. Current CS users and those who stopped CS treatment <6
      months earlier also reported bruises to be among their most frequent and
      distressing symptoms. Twenty-five of the 33 symptoms occurred more frequently in
      current CS users than in nonusers, and 30 symptoms occurred more frequently in
      current users than in previous users who had stopped CS use >or=6 months earlier.
      Symptom occurrence was significantly greater for current users compared with
      those who stopped CS use <6 months earlier for puffy face (q = 0.003), excessive
      appetite (q = 0.002), changed facial features (q = 0.033), and buffalo hump (q =
      0.048). Patients who had stopped CS use <6 months earlier reported 20 of the 33
      symptoms significantly more often than those who had stopped CS use >or=6 months
      earlier (q < 0.05). The only symptoms reported significantly more often in
      patients who had stopped CS use >or=6 months earlier compared with nonusers were
      buffalo hump and bruises (q < 0.05). The distress associated with bruises was
      significantly higher in current users compared with nonusers and compared with
      previous users who had stopped CS use >or=6 months earlier (both, q = 0.047).
      Current users also reported significantly greater distress than nonusers for
      puffy face and excessive appetite (both, q = 0.047). Changed facial features was
      significantly more distressing in current users compared with those who had
      stopped CS use >or=6 months earlier (q = 0.047). CONCLUSIONS: Different symptom
      profiles emerged based on the pattern of CS use. Patients who were currently
      using CS or who had stopped CS treatment <6 months earlier reported more symptoms
      than did patients who had never received CS or who had stopped CS treatment =6
      months earlier.

PMID- 18803996
TI  - Optimal frequency for measuring health care resource utilization in Parkinson's
      disease using participant recall: the FS-TOO resource utilization substudy.
AB  - OBJECTIVE: The aim of this substudy was to determine the agreement between 2
      approaches for measuring health care resource utilization (eg, number of hospital
      visits, number of primary care physician visits) in trial participants with
      Parkinson's disease (PD). METHODS: A substudy of the 1-year multicenter futility
      trial of GPI-1,485 and coenzyme Q(10) (FS-TOO) was performed to assess health
      care resource utilization agreement by measuring participant utilization recall
      after 12 months versus measuring participant utilization recall at regular 3
      month intervals. Trial participants were selected from patients in the National
      Institutes of Health-sponsored FS-TOO multicenter study. Persons aged >or=30
      years with confirmed PD diagnosis within the previous 5 years were eligible for
      inclusion in the substudy. Participants were also required to have at least 2 of
      3 cardinal manifestations of PD (tremor, rigidity, and bradykinesia).
      Participants were excluded from the study if they had presence of atypical
      Parkinson's syndromes due to drugs, metabolic identified neurogenetic disorders,
      encephalitis, or other degenerative diseases. Agreement was determined using
      Lin's concordance and Cohen's kappa statistics. RESULTS: Between March and July
      of 2004, a total of 424 potential subjects were identified and evaluated for
      trial eligibility. Of these, 213 subjects (139 men, 74 women; mean [SD] age, 61.5
      [10.3] years) met entry criteria and were included in the study. Trial
      participants were randomized equally to 1 of 3 groups. The 3 groups had similar
      baseline characteristics in terms of demographic data (age, race, sex, employment
      status, and annual income), total Unified Parkinson Disease Rating Scale (UPDRS)
      score, and UPDRS subscores. In this substudy, 141 participants had a true
      baseline visit, indicating a clinical baseline date, and 182 participants
      completed the Baseline Resource Utilization Form within 3 months of the true
      baseline visit. The comparison of concordance between the summed information over
      3-month recalls and the 12-month recall from baseline was derived from these 182
      participants. The level of agreement between the 2 approaches was high, ranging
      from 64.4% to 95.1%. Where disagreement was identified, the more frequent
      measurement approach (every 3 months) led to higher estimates, ranging from 20.4%
      to 77.4%. CONCLUSION: The results of this trial indicate internal consistency
      with the self-reported measures of health care resource utilization, suggesting
      that these simple measures might provide reliable information about units of
      health care resource utilization in the context of clinical trials for PD.

PMID- 18803997
TI  - Adherence with multiple-combination antihypertensive pharmacotherapies in a US
      managed care database.
AB  - OBJECTIVE: The aim of this analysis was to assess the impact of multiple
      combination therapies on medication possession ratios (MPRs) in an
      antihypertensive naive population. METHODS: Data were collected using the
      Integrated Healthcare Information Solution's National Benchmark Database (January
      1997 to June 2004). Data from patients who received 2-pill pharmacotherapy with
      valsartan or valsartan/hydrochlorothiazide (HCTZ) in a fixed-dose combination
      (FDC) + amlodipine were compared with those from patients who received 3-pill
      therapy with valsartan + HCTZ + amlodipine as 3 free-drug components. MPR was
      calculated by dividing the total days' supply for the lower value in the case of
      individual drug components, or the number of days' supply in the case of FDC, by
      365 (the number of days during the 1-year study period the medication regimen was
      prescribed). A general linear regression was then performed to determine the
      effect of treatment group on MPR, controlling for the demographic and clinical
      characteristics. RESULTS: Data from 908 patients were included (527 women, 381
      men; mean age, 53.9 years; 2-pill treatment with valsartan + amlodipine, 224
      patients; 2-pill treatment with valsartan/HCTZ + amlodipine, 619; and 3-pill
      therapy with valsartan + HCTZ + amlodipine, 65). The MPR values were 75.4%,
      73.1%, and 60.5%, respectively (P = 0.005). MPR improved with age (69.6% in the
      subset aged 18-<36 years vs 75.2% in the subset aged >or=64 years; P = 0.023).
      CONCLUSIONS: In these antihypertensive-naive patients with hypertension, MPR
      decreased with the increase in tablets per regimen, and improved MPR was
      correlated with increasing age. These findings suggest patient compliance
      improves with simplified pharmacotherapeutic approaches.

PMID- 18803998
TI  - Introduction to cervical outcomes measures: state of the art.

PMID- 18803999
TI  - The Neck Disability Index: state-of-the-art, 1991-2008.
AB  - BACKGROUND: Published in 1991, the Neck Disability Index (NDI) was the first
      instrument designed to assess self-rated disability in patients with neck pain.
      This article reviews the history of the NDI and the current state of the research
      into its psychometric properties--reliability, validity, and responsiveness--as
      well as its translations. Focused reviews are presented into its use in studies
      of the prognosis of whiplash-injured patients as well as its use in clinical
      trials of conservative therapies for neck pain. SPECIAL FEATURES: The NDI is a
      relatively short, paper-pencil instrument that is easy to apply in both clinical
      and research settings. It has strong psychometric characteristics and has proven
      to be highly responsive in clinical trials. As of late 2007, it has been used in
      approximately 300 publications; it has been translated into 22 languages, and it
      is endorsed for use by a number of clinical guidelines. SUMMARY: The NDI is the
      most widely used and most strongly validated instrument for assessing self-rated
      disability in patients with neck pain. It has been used effectively in both
      clinical and research settings in the treatment of this very common problem.

PMID- 18804000
TI  - Cervical motion testing: methodology and clinical implications.
AB  - BACKGROUND: Measurement of cervical motion (CM) is probably the most commonly
      applied functional outcome measure in assessing the status of patients with
      cervical pathology. In general terms, CM refers to motion of the head relative to
      the trunk as well as conjunct motions within the cervical spine. SPECIAL
      FEATURES: Multiple techniques and instruments have been used for assessing CM.
      These were associated with a wide variety of parameters relating to accuracy,
      reproducibility, and validity. Modern measurement systems enable recording,
      processing, and documentation of CM with a high degree of precision. SUMMARY:
      Cervical motion measures provide substantial information regarding the severity
      of motion limitation and level of effort in cervically involved patients. They
      may also be used for following up performance during and after conservative or
      invasive interventions.

PMID- 18804001
TI  - Measurement of cervical posture in the sagittal plane.
AB  - BACKGROUND: This article provides a historical perspective and an overview of
      different ways of measuring sagittal plane cervical posture in clinical and
      research settings. SPECIAL FEATURES: Measures of cervical posture are considered,
      in terms of their purpose, their reliability and validity, and their capacity to
      provide knowledge about cervical posture. SUMMARY: Despite technological advances
      in measurement techniques, there is still much to learn about cervical posture in
      terms of understanding how the neck balances the head against the force of
      gravity. The individual spinal segments of the neck assume different relative
      positions, depending on the individual's genetics; anatomical construction;
      occupational demands; muscle strength and endurance; as well as mental state,
      personality, and culture. Valid measures which can capture this objectively and
      reliably continue to challenge clinicians and researchers.

PMID- 18804002
TI  - Cervical muscles strength testing: methods and clinical implications.
AB  - BACKGROUND: Neck muscles are responsible for directing the head and for
      maintaining its posture. As a result, the muscular mechanical output is
      correspondingly moderate but not insignificant as evidenced by a positive
      therapeutic effect when reconditioning is indicated. SPECIAL FEATURES: Cervical
      muscle strength (CS) measurement and interpretation occupy a unique niche in the
      domain of muscle performance. Due to the wide variety of devices and protocols, a
      vast range of strength scores has been reported, denying the formation of
      reliable reference values. METHODS: A literature search based on the keywords
      "cervical/head/neck" strength was conducted. The search yielded 34 relevant
      papers which were reviewed according to preset criteria. SUMMARY: Overall studies
      indicate that compared to normal subjects patients suffering from neck-related
      disorders present with significant reduction in CS, whereas women are weaker than
      men by about 40%. Noteworthy a significant drop in CS in both sexes is delayed
      until the seventh decade. In terms of its reproducibility, CS findings have been
      investigated using primarily relative parameters, and hence, the associated error
      is not yet established. Therefore, application of CS as a clinical outcome
      measure, particularly for assessing change due to intervention, should be
      critically conducted.

PMID- 18804003
TI  - Clinical assessment of the deep cervical flexor muscles: the craniocervical
      flexion test.
AB  - BACKGROUND: The craniocervical flexion test (CCFT) is a clinical test of the
      anatomical action of the deep cervical flexor muscles, the longus capitis, and
      colli. It has evolved over 15 years as both a clinical and research tool and was
      devised in response to research indicating the importance of the deep cervical
      flexors in support of the cervical lordosis and motion segments and clinical
      observations of their impairment with neck pain. SPECIAL FEATURES: The CCFT could
      be described as a test of neuromotor control. The features assessed are the
      activation and isometric endurance of the deep cervical flexors as well as their
      interaction with the superficial cervical flexors during the performance of five
      progressive stages of increasing craniocervical flexion range of motion. It is a
      low-load test performed in the supine position with the patient guided to each
      stage by feedback from a pressure sensor placed behind the neck. While the test
      in the clinical setting provides only an indirect measure of performance, the
      construct validity of the CCFT has been verified in a laboratory setting by
      direct measurement of deep and superficial flexor muscle activity. SUMMARY:
      Research has established that patients with neck pain disorders, compared to
      controls, have an altered neuromotor control strategy during craniocervical
      flexion characterized by reduced activity in the deep cervical flexors and
      increased activity in the superficial flexors usually accompanied by altered
      movement strategies. Furthermore, they display reduced isometric endurance of the
      deep cervical flexor muscles. The muscle impairment identified with the CCFT
      appears to be generic to neck pain disorders of various etiologies. These
      observations prompted the use of the craniocervical flexion action for retraining
      the deep cervical flexor muscles within a motor relearning program for neck pain
      patients, which has shown positive therapeutic benefits when tested in clinical
      trials.

PMID- 18804004
TI  - Testing for sensory hypersensitivity or central hyperexcitability associated with
      cervical spine pain.
AB  - BACKGROUND: Sensory hypersensitivity is a recently recognized yet common feature
      of some neck pain conditions, particularly those with higher levels of pain and
      disability. It is generally acknowledged that the presence of widespread sensory
      hypersensitivity provides indication of augmented central pain processing
      mechanisms or central hyperexcitability. Sensory hypersensitivity may be able to
      differentiate various neck pain conditions, provide an indication of prognosis
      after whiplash injury, and show potential to recognize poor responders to
      physical interventions. SPECIAL FEATURES: Various tests may be used to determine
      the presence of sensory hypersensitivity. This article outlines and discusses 3
      tests that have been used in the investigation of processes underlying neck pain
      as follows: pressure pain thresholds (PPT); thermal pain thresholds, and the
      brachial plexus provocation test. SUMMARY: Although there are some data available
      on the psychometric properties of these tests, particularly PPT, much more
      information is required before these tests can be comprehensively used in the
      clinical environment.

PMID- 18804005
TI  - Cervical outcome measures: testing for postural stability and balance.
AB  - BACKGROUND: Clinical tests assessing a correlation between structural pathology
      and cervical pain have been unsuccessful, leading the way for the development of
      functionally based tests. The purpose of this narrative is to review 4 promising
      functional tests for the assessment of sensorimotor dysfunction in patients with
      neck pain. The Joint Position Error/Head Repositioning Accuracy tests, and the
      Rod and Frame Test were reviewed. SPECIAL FEATURES: The SPNTT was developed to
      test proprioceptive mechanisms in the neck by applying torsion to mainly
      mechanoreceptors in the cervical spine. The Joint Position Error and Head
      Repositioning Accuracy test cervicocephalic kinesthesia or the ability to
      perceive both movement and position of the head in space related to the trunk.
      The Rod and Frame Test assesses patients' perception of the vertical orientation
      of their head in 3-dimensional space. All of these tests evaluate important
      mechanisms responsible for maintaining postural stability and balance and are
      thought to be applicable for use in mechanical neck pain patients. SUMMARY: All
      of the reviewed tests show clinical promise because they are able to distinguish
      patients with neck pain, particularly those with whiplash trauma and dizziness
      from asymptomatic controls. All of the tests assess cervical sensorimotor
      dysfunction, although considerably more research is needed to more clearly
      establish the psychometric properties for each test including minimal clinical
      important difference. Although these tests can be used in routine clinical
      practice, they should be used in combination with other related tests.

PMID- 18804006
TI  - Undershooting of a neutral reference position by asymptomatic subjects after
      cervical motion in the sagittal plane.
AB  - OBJECTIVE: The objective of this study was to determine if blindfolded,
      asymptomatic subjects undershoot or overshoot a self-selected neutral reference
      position (NRP) when performing a full-cycle, head repositioning accuracy test in
      the sagittal plane. METHODS: An asymptomatic group of subjects, consisting of 7
      men and 5 women with no history of head and neck pain, were recruited for the
      study. Subjects, performing a full-cycle series of head/neck movements in the
      sagittal plane, attempted to return to a self-selected NRP, defined at the
      beginning of the movement sequence, without benefit of visual clues. Data were
      collected for each subject, and repositioning errors were calculated. The sign of
      the error was used to determine if undershooting or overshooting of the NRP had
      occurred. RESULTS: Subjects undershot a self-selected NRP at statistically
      significant levels (P < .01) when performing the head repositioning accuracy test
      while blindfolded. Subjects undershot the NRP 83% of the time when moving from
      flexion to the NRP and undershot the NRP 92% of the time when moving from
      extension to the NRP. A Fisher exact test showed no significant difference
      between the number of times subjects undershot the NRP when moving from either
      flexion to the NRP or from extension to the NRP. To our knowledge, neither
      undershooting nor overshooting of an NRP has previously been reported for
      asymptomatic subjects at statistically significant levels. CONCLUSION: Knowing
      that asymptomatic subjects undershoot an NRP may help to direct treatment and
      rehabilitation of patients who have experienced whiplash-type injuries and are
      shown to overshoot the NRP when performing the same test.

PMID- 18804007
TI  - Cervical myelopathy: a case report of a "near-miss" complication to cervical
      manipulation.
AB  - OBJECTIVE: Cases have been reported in which radiculopathy or myelopathy
      secondary to herniated disk has occurred after cervical manipulation. In each
      case, it is not possible to determine whether the neurologic symptoms and signs
      were directly caused by the manipulation or whether they developed as part of the
      natural history of the disorder. The purpose of this article is to report a case
      in which a patient with radiculopathy secondary to herniated disk was scheduled
      to receive manipulation but just before receiving this treatment developed acute
      myelopathy. CLINICAL FEATURES: A patient with arm pain and numbness was referred
      by a neurosurgeon for nonsurgical consult. He had a large C5-6 disk herniation
      with no signs or symptoms of myelopathy. He was determined to be a candidate for
      nonsurgical intervention, including manipulation. Manipulative treatment was
      planned for the second visit. INTERVENTION AND OUTCOME: Ten days after the
      initial visit, and before any manipulative treatment being rendered, the patient
      developed symptoms suggestive of myelopathy, which were later determined on
      examination to be related to acute myelopathy secondary to the disk herniation.
      CONCLUSION: Herniated disk in the cervical spine can progress to myelopathy as
      part of the natural history of this condition. Because of this, any
      interpretation of myelopathy that occurs after cervical manipulation, or any
      other procedure, must be made with caution.

PMID- 18804008
TI  - Expression of concern: plagiarism in a case report.

PMID- 18804009
TI  - Blood sampling through intraosseous needles: time to stop?

PMID- 18804010
TI  - The chromosome shuffle.

PMID- 18804011
TI  - [7th Congress of the French Society of Vascular Medicine, 2-4 October 2008, Nice
      Acropolis, France. Abstracts].

PMID- 18804013
TI  - Challenges and costs related to recruitment of female adolescents for clinical
      research.
AB  - Addressing health issues in adolescents is a national priority. However,
      recruitment of adolescents into research studies can be challenging and costly.
      The purpose of this article was to compare procedures, costs, and challenges in
      recruiting female adolescents from two hospitals and two high schools in an urban
      area of the southern United States. Three studies will be described. The findings
      indicate that the choice of recruitment procedures and sites has major
      implications for study budget in terms of personnel time as well as for the
      timeline of the study.

PMID- 18804014
TI  - Childhood obesity: a transtheoretical case management approach.
AB  - Childhood obesity is an increasing health problem because of its strong
      associations with chronic health problems in children and adults. Obesity during
      childhood commonly persists into adulthood and is resistant to interventions that
      involve only recommendations to decrease caloric intake and to increase caloric
      expenditure through increased physical activity. The challenge with this approach
      to childhood obesity is that it is not theoretically based, nor does it consider
      the child's or the parent's perceptions of the health problem or their transition
      along the stages of behavioral change. Case management has been proven to be
      successful in managing various chronic health problems in both adults and
      children. This article will introduce a new intervention model based on the
      transtheoretical framework by utilizing case management in a primary care setting
      to treat childhood obesity.

PMID- 18804015
TI  - Attention deficit/hyperactivity disorder: a review and update.
AB  - Attention deficit/hyperactivity disorder (ADHD) is a prevalent, chronic, and
      pervasive childhood disorder characterized by developmentally inappropriate
      activity level, impulsivity, and inability to sustain attention and
      concentration. Core symptoms of the disorder are associated with impairment in
      multiple domains of functioning and often coexist with other psychiatric
      disorders, the most prevalent being oppositional defiant disorder, conduct
      disorder, depression, and anxiety disorders. Concerns have been expressed about
      the overdiagnosis of ADHD, an upsurge in prescription of stimulant medication,
      and wide variations in practice patterns related to diagnosis and treatment of
      children with ADHD among primary care providers. Clinical research and expert
      consensus guidelines over the past decade have increasingly clarified the most
      effective approaches to diagnosis and treatment of the disorder. Hence, the
      purpose of this article was to provide primary care providers with the most
      current, evidence-based information on the assessment and treatment of children
      with ADHD.

PMID- 18804016
TI  - Preliminary evidence of an adolescent HIV/AIDS peer education program.
AB  - Adolescent peer education has been found to be an effective method to improve
      adolescents' knowledge and positive health behaviors. The purpose of this study
      was to determine the extent to which a peer education program was effective in
      changing adolescents' HIV/AIDS knowledge, risk behavior intentions, and
      confidence to engage in safe sex. The results showed that there was a significant
      difference in HIV knowledge between the peer education group and the
      traditionally educated group, with the peer group demonstrating greater
      knowledge. There was no significant difference in confidence to engage in safe
      sex between the two groups, but students in the intervention group were more
      likely to engage in safe sex than students in the traditionally educated group.
      Nurses can provide leadership in the development, implementation, and evaluation
      of peer education in adolescent health.

PMID- 18804017
TI  - The experience of being an Asthma Amigo in a program to decrease asthma episodes
      in Hispanic children.
AB  - Asthma is the most common chronic illness among Latino children in urban areas.
      It is especially problematic for schools serving low-income and minority
      populations. The purpose of this study was to describe the experience of being an
      Asthma Amigo, a community-based educator who delivered asthma education to a
      Hispanic community in a train-the-trainer educational model. Focus group process
      evaluation was used to assess participant experiences and program strengths and
      weaknesses. Findings suggested that being an Asthma Amigo helped in gaining
      entree into the community and in spreading the message of asthma triggers and
      prevention.

PMID- 18804018
TI  - The lived experience of fathers who have children with asthma: a phenomenological
      study.
AB  - Asthma is a common chronic illness of childhood and a major cause of school
      absenteeism and hospitalization. When a child is diagnosed with asthma, parents
      become responsible for the long-term management of a chronic condition that is
      characterized by unpredictable and irregular episodes. Much of the research
      concerning parenting children who have asthma had focused on mothers. Paternal
      experiences in caring for a child with asthma have received little attention. In
      this phenomenological study, van Manen's (Researching Lived Experience: Human
      Science for an Action Sensitive Pedagogy. The Althouse Press: London, ON) method
      of inquiry was used to explore the lived experience of fathers who have children
      with asthma. Eight fathers with children aged between 7 and 11 years who had been
      diagnosed with asthma were interviewed. Five themes were identified: feeling
      relief in knowing the diagnosis, learning the ropes, being vigilant, living with
      concern, and being comfortable with asthma management. Understanding the
      experience of fathers who have children with asthma and gaining insight into
      their needs and concerns are essential first steps to providing supportive
      nursing care.

PMID- 18804019
TI  - The Federal Deficit Reduction Act and its impact on children.
AB  - The Deficit Reduction Act of 2005 makes changes in the Medicaid program that may
      have a significant effect on children's health. Nurses and other health care
      professionals should be aware of these changes in order to monitor the impact of
      the legislation, guide families in the process of accessing needed services, and
      advocating on behalf of children and families.

PMID- 18804020
TI  - Safe homes.

PMID- 18804021
TI  - Use of the anal plug in the treatment of fecal incontinence in patients with
      meningomyelocele.
AB  - BACKGROUND: Children with meningomyelocele (MMC) commonly present with urinary
      and fecal incontinence. Despite bowel training and enemas, many still suffer from
      fecal soiling, which may cause skin irritation and malodor. Fear and
      embarrassment may cause some of these children to avoid partaking in social
      activities. The anal plug (AP), an anal tampon, has been developed to prevent
      fecal soiling. The purpose of this study was to evaluate the use of the AP in
      children with MMC with regard to reduction of fecal soiling and impact on social
      functioning. METHODS: Twenty children and young adults with MMC, neurological
      level L(5) or proximal, participated in the study. MAIN OUTCOME MEASURES: Number
      of incidents of fecal soiling, degree of comfort of the accessory of choice, and
      impact of fecal soiling on social functioning were used as the main outcome
      measures for this study. INTERVENTION: Each participant kept a daily diary
      reporting on each of the outcome measures over the course of 5 weeks. The first
      week, prior to intervention with the AP, was used as the base control for each
      patient. Over three sessions, the use of the AP was explained and demonstrated,
      after which it was given to the participants to be used. RESULTS: Seventy-five
      percent of the participants completed the study. There was a significant
      improvement in all outcome parameters following the intervention. The median
      number of weekly incidents of soiling dropped from 4 to 0 (p = .002). The median
      reported effect of fecal soiling on social integration before the use of the AP
      was found to be very bothersome, whereas during the use of the AP, it was barely
      bothersome (p = .004). CONCLUSION: Use of the AP in children and young adults
      with MMC can prevent fecal soiling and promote "social continence."

PMID- 18804022
TI  - Enteral feeding in neurologically impaired children with gastroesophageal reflux:
      Nissen fundoplication and gastrostomy tube placement versus percutaneous
      gastrojejunostomy.
AB  - Parents or caregivers of neurologically impaired children with gastroesophageal
      reflux who require enteral nutrition are often faced with the option of having
      their child undergo an antireflux surgery and placement of a gastrostomy tube or
      have a percutaneous gastrojejunostomy tube placed under fluoroscopic guidance. It
      is important that nurses have an understanding of these procedures and their
      associated risks and benefits as well as knowledge of the impact each might have
      on the daily life and care of these children to help support families during this
      decision-making process.

PMID- 18804023
TI  - Double whammy: bispecific antibodies help immune cells attack tumors.

PMID- 18804024
TI  - Friend or foe? Turning a host defense protein into a pathogen's accomplice.
AB  - Cystatins are cysteine protease inhibitors that are at the front-line of defense
      against pathogens that secrete proteases as virulence factors. In this issue,
      Vincents et al. (2008) reveal how the bacterial protease IdeS from Streptococcus
      pyogenes hijacks normal cystatin C function to convert it into a cofactor that
      enhances proteolytic destruction of host-defense antibodies.

PMID- 18804025
TI  - Mass spectrometry and the emerging field of glycomics.
AB  - The biological significance of protein and lipid glycosylation is well
      established. For example, cells respond to environmental stimuli by altering
      glycan structures on their surfaces, and cancer cells evade normal growth
      regulation in part by remodeling their surface glycans. In general, glycan
      chemical properties differ significantly from those of proteins, lipids, nucleic
      acids, and small molecule metabolites. Thus, advances in glycomics, a
      comprehensive study to identify all glycans in an organism, rely on the
      development of specialized analytical methods. Mass spectrometry (MS) is emerging
      as an enabling technology in the field of glycomics. This review summarizes
      recent developments in mass spectrometric analysis methods for protein-based
      glycomics and glycoproteomics workflows.

PMID- 18804026
TI  - Human symbiont Bacteroides thetaiotaomicron synthesizes 2-keto-3-deoxy-D-glycero
      D- galacto-nononic acid (KDN).
AB  - The proper functioning of the human intestine is dependent on its bacterial
      symbionts, the most predominant of which belong to the Phylum Bacteroidetes.
      These bacteria are known to use variable displays of multiple capsular
      polysaccharides (CPs) to aid in their survival and foraging within the intestine.
      Bacteroides thetaiotaomicron is a prominent human gut symbiont and a remarkably
      versatile glycophile. The structure determination of the CPs, encoded by the
      eight CP loci, is the key to understanding the mechanism of this organism's
      adaptation on a molecular level. Herein, we report the bioinformatics-based
      discovery and chemical demonstration of a biosynthetic pathway that forms and
      cytidylates 2-keto-3-deoxy-D-glycero-D-galacto-nononic acid (KDN), most likely
      for inclusion in the CP encoded by B. thetaiotaomicron CP locus 7.

PMID- 18804027
TI  - Biosynthesis of the cyclooligomer depsipeptide beauvericin, a virulence factor of
      the entomopathogenic fungus Beauveria bassiana.
AB  - Beauvericin, a cyclohexadepsipeptide ionophore from the entomopathogen Beauveria
      bassiana, shows antibiotic, antifungal, insecticidal, and cancer cell
      antiproliferative and antihaptotactic (cell motility inhibitory) activity in
      vitro. The bbBeas gene encoding the BbBEAS nonribosomal peptide synthetase was
      isolated from B. bassiana and confirmed to be responsible for beauvericin
      biosynthesis by targeted disruption. BbBEAS utilizes D-2-hydroxyisovalerate (D
      Hiv) and L-phenylalanine (Phe) for the iterative synthesis of a predicted N
      methyl-dipeptidol intermediate, and forms the cyclic trimeric ester beauvericin
      from this intermediate in an unusual recursive process. Heterologous expression
      of the bbBeas gene in Escherichia coli to produce the 3189 amino acid, 351.9 kDa
      BbBEAS enzyme provided a strain proficient in beauvericin biosynthesis.
      Comparative infection assays with a BbBEAS knockout B. bassiana strain against
      three insect hosts revealed that beauvericin plays a highly significant but not
      indispensable role in virulence.

PMID- 18804028
TI  - A heterospecific leucine zipper tetramer.
AB  - Protein-protein interactions play an essential role in the assembly of the
      macromolecular complexes that form functional networks and control cellular
      behavior. Elucidating principles of molecular recognition governing potentially
      complex interfaces is a challenging goal for structural and systems biology.
      Extensive studies of alpha-helical coiled coils have provided fundamental insight
      into the determinants of one seemingly tractable class of oligomeric protein
      interfaces. We report here that two different valine-containing mutants of the
      GCN4 leucine zipper that fold individually as four-stranded coiled coils
      associate preferentially in mixtures to form an antiparallel, heterotetrameric
      structure. X-ray crystallographic analysis reveals that the coinciding
      hydrophobic interfaces of the hetero- and homotetramers differ in detail, thereby
      controlling their partnering and structural specificity. Equilibrium disulfide
      exchange and thermal denaturation experiments show that the 50-fold preference
      for heterospecificity is determined by interfacial van der Waals interactions and
      hydrophobicity. Parallel studies of two alanine-containing variants confirm the
      above-mentioned interpretation of the basis and mechanism of this
      heterospecificity. Our results suggest that coiled-coil recognition is an
      inherently geometric process in which heterotypic interaction specificity derives
      from a complementarity of both shape and chemistry.

PMID- 18804029
TI  - Structure-based dissection of the active site chemistry of leukotriene A4
      hydrolase: implications for M1 aminopeptidases and inhibitor design.
AB  - M1 aminopeptidases comprise a large family of biologically important zinc
      enzymes. We show that peptide turnover by the M1 prototype, leukotriene A4
      hydrolase/aminopeptidase, involves a shift in substrate position associated with
      exchange of zinc coordinating groups, while maintaining the overall coordination
      geometry. The transition state is stabilized by residues conserved among M1
      members and in the final reaction step, Glu-296 of the canonical zinc binding
      HEXXH motif shuffles a proton from the hydrolytic water to the leaving group.
      Tripeptide substrates bind along the conserved GXMEN motif, precisely occupying
      the distance between Glu-271 and Arg-563, whereas the Arg specificity is governed
      by a narrow S1 pocket capped with Asp-375. Our data provide detailed insights to
      the active site chemistry of M1 aminopeptidases and will aid in the development
      of novel enzyme inhibitors.

PMID- 18804030
TI  - Loss of a mycobacterial gene encoding a reductase leads to an altered cell wall
      containing beta-oxo-mycolic acid analogs and accumulation of ketones.
AB  - Mycolic acids are essential components of the mycobacterial cell wall. In this
      study, we show that a gene encoding a reductase involved in the final step of
      mycolic acid biosynthesis can be deleted in Mycobacterium smegmatis without
      affecting cell viability. Deletion of MSMEG4722 (ortholog of Mycobacterium
      tuberculosis Rv2509) altered culture characteristics and antibiotic sensitivity.
      The DeltaMSMEG4722 strain synthesized alpha-alkyl, beta-oxo intermediates of
      mycolic acids, which were found esterified to cell wall arabinogalactan. While
      the precursors could not be isolated directly due to their inherent instability
      during base treatment, their presence was established by prior reduction of the
      beta-oxo group by sodium borohydride. Interestingly, the mutant also accumulated
      unsaturated ketones, similar to tuberculenone from M. tuberculosis, which were
      shunt products derived from spontaneous decarboxylation of alpha-alkyl, beta-oxo
      fatty acid precursors of mycolic acids.

PMID- 18804031
TI  - Design of peptide inhibitors for the importin alpha/beta nuclear import pathway
      by activity-based profiling.
AB  - Despite the current availability of selective inhibitors for the classical
      nuclear export pathway, no inhibitor for the classical nuclear import pathway has
      been developed. Here we describe the development of specific inhibitors for the
      importin alpha/beta pathway using a novel method of peptide inhibitor design. An
      activity-based profile was created via systematic mutational analysis of a
      peptide template of a nuclear localization signal. An additivity-based design
      using the activity-based profile generated two peptides with affinities for
      importin alpha that were approximately 5 million times higher than that of the
      starting template sequence. The high affinity of these peptides resulted in
      specific inhibition of the importin alpha/beta pathway. These peptide inhibitors
      provide a useful tool for studying nuclear import events. Moreover, our inhibitor
      design method should enable the development of potent inhibitors from a peptide
      seed.

PMID- 18804032
TI  - Functional analysis of MycCI and MycG, cytochrome P450 enzymes involved in
      biosynthesis of mycinamicin macrolide antibiotics.
AB  - Macrolides are a class of valuable antibiotics that include a macrolactone ring,
      at least one appended sugar unit, and, in most cases, additional hydroxyl or
      epoxide groups installed by cytochrome P450 enzymes. These functional groups
      contribute to structural diversification and serve to improve the bioactivity
      profiles of natural products. Here, we have characterized in vitro two P450
      enzymes from the mycinamicin biosynthetic pathway of Micromonospora griseorubida.
      First, MycCI was characterized as the C21 methyl hydroxylase of mycinamicin VIII,
      the earliest macrolide form in the postpolyketide synthase tailoring pathway.
      Moreover, we established that optimal activity of MycCI depends on the native
      ferredoxin MycCII. Second, MycG P450 catalyzes consecutive hydroxylation and
      epoxidation reactions with mycinamicin IV as initial substrate. These reactions
      require prior dimethylation of 6-deoxyallose to mycinose for effective conversion
      by the dual function MycG enzyme.

PMID- 18804033
TI  - The human protease inhibitor cystatin C is an activating cofactor for the
      streptococcal cysteine protease IdeS.
AB  - Human cystatin C is considered the physiologically most important inhibitor of
      endogenous papain-like cysteine proteases. We present here an unexpected function
      of cystatin C. Instead of acting as an inhibitor, cystatin C acts as a
      facultative, endogenous cofactor for the papain-like IgG-cleaving enzyme IdeS of
      the human pathogen Streptococcus pyogenes. IdeS activity is not dependent on
      cystatin C, but is significantly enhanced in the presence of cystatin C. We
      report a protease inhibitor that accelerates the activity of its putative target
      protease and a unique example of how a host protease inhibitor is "hijacked" by a
      bacterial protease to increase its activity. This finding has important
      implications for the view on protease-inhibitor interactions, and is relevant to
      consider in the therapeutic use of protease inhibitors.

PMID- 18804034
TI  - Identification of chemical inhibitors to human tissue transglutaminase by
      screening existing drug libraries.
AB  - Human tissue transglutaminase (TGM2) is a calcium-dependent crosslinking enzyme
      involved in the posttranslational modification of intra- and extracellular
      proteins and implicated in several neurodegenerative diseases. To find specific
      inhibitors to TGM2, two structurally diverse chemical libraries (LOPAC and
      Prestwick) were screened. We found that ZM39923, a Janus kinase inhibitor, and
      its metabolite ZM449829 were the most potent inhibitors with IC(50) of 10 and 5
      nM, respectively. In addition, two other inhibitors, including tyrphostin 47 and
      vitamin K(3), were found to have an IC(50) in the micromolar range. These agents
      used in part a thiol-dependent mechanism to inhibit TGM2, consistent with the
      activation of TGM2 by reduction of an intramolecular disulfide bond. These
      inhibitors were tested in a polyglutamine-expressing Drosophila model of
      neurodegeneration and found to improve survival. The TGM2 inhibitors we
      discovered may serve as valuable lead compounds for the development of orally
      active TGM2 inhibitors to treat human diseases.

PMID- 18804035
TI  - Directed evolution of streptavidin variants using in vitro compartmentalization.
AB  - We have developed and implemented an in vitro compartmentalization (IVC)
      selection scheme for the identification of streptavidin (SA) variants with
      altered specificities for the biotin analog desthiobiotin. Wild-type SA and
      selected variants bind desthiobiotin with similar affinities (approximately 10(
      13) M), but the variants have off rates almost 50 times slower and a half-life
      for dissociation of 24 hr at 25 degrees C. The utility of streptavidin variants
      with altered specificities and kinetic properties was shown by constructing
      protein microarrays that could be used to differentially organize and immobilize
      DNAs bearing these ligands. The methods we have developed should prove to be
      generally useful for generating a variety of novel SA reagents and for evolving
      other extremely high-affinity protein:ligand couples.

PMID- 18804036
TI  - Structure-guided development of efficacious antifungal agents targeting Candida
      glabrata dihydrofolate reductase.
AB  - Candida glabrata is a lethal fungal pathogen resistant to many antifungal agents
      and has emerged as a critical target for drug discovery. Over the past several
      years, we have been developing a class of propargyl-linked antifolates as
      antimicrobials and hypothesized that these compounds could be effective
      inhibitors of dihydrofolate reductase (DHFR) from C. glabrata. We initially
      screened a small collection of these inhibitors and found modest levels of
      potency. Subsequently, we determined the crystal structure of C. glabrata DHFR
      bound to a representative inhibitor with data to 1.6 A resolution. Using this
      structure, we designed and synthesized second-generation inhibitors. These
      inhibitors bind the C. glabrata DHFR enzyme with subnanomolar potency, display
      greater than 2000-fold levels of selectivity over the human enzyme, and inhibit
      the growth of C. glabrata at levels observed with clinically employed
      therapeutics.

PMID- 18804037
TI  - Cell-based therapies for osteonecrosis of the femoral head.
AB  - Osteonecrosis of the femoral head is a disabling condition and a known
      complication of hematopoietic cell transplants (HCT). It is characterized by
      empty lacunae in the osseous matrix and necrotic marrow elements. The most
      important risk factor in HCT recipients is steroid exposure, frequently in the
      context of graft-versus-host disease. Current treatment is surgical, and involves
      decompression of the affected area and the use of bone grafts or hip
      arthroplasty. Cellular-based therapies are now under investigation, and can be
      used in addition to, or instead of, invasive surgery. This review presents an
      overview of osteonecrosis with particular emphasis on HCT recipients and
      introduces the role of cell therapy, especially with mesenchymal stromal cells,
      as a promising new treatment.

PMID- 18804038
TI  - Combination therapy using IL-2 and anti-CD25 results in augmented natural killer
      cell-mediated antitumor responses.
AB  - Interleukin (IL)-2 has been extensively examined to promote clinical T and
      natural killer (NK) cell responses. Regulatory T cells (Tregs) have been shown to
      regulate many aspects of the immune system, including NK cell-mediated responses.
      We have demonstrated that in vivo administration of IL-2 led to activation and
      expansion of both NK cells and immunosuppressive Tregs. Therefore, we attempted
      to augment NK cell antitumor effects by concurrently depleting Tregs using anti
      CD25. Increased NK cell activation by IL-2 was found to be correlated with an
      increase in classical, short-term NK cell in vitro killing assays regardless of
      the depletion of Tregs. But when splenocytes of the treated mice were used in
      long-term tumor outgrowth experiments, we observed that prior depletion of Tregs
      from IL-2 administration led to improved antitumor effects compared with either
      treatment alone. Importantly, these in vitro data are correlated with subsequent
      in vivo survival of leukemia-bearing mice, in which co-treatment of IL-2 with
      anti-CD25 led to significantly improved survival compared with mice treated with
      either IL-2 alone or with Treg depletion. Prior depletion of NK1.1(+) cells, but
      not of CD8(+) cells, completely abrogated all antitumor effects mediated by IL-2
      and anti-CD25 combination therapy. These findings demonstrate that superior NK
      cell-mediated antileukemic effects can be achieved with IL-2 administration and
      concurrent depletion of CD25(+) cells.

PMID- 18804039
TI  - Central nervous system relapse of leukemia after allogeneic hematopoietic stem
      cell transplantation.
AB  - Little information is available regarding central nervous system (CNS) relapse of
      adult leukemia after allogeneic hematopoietic stem cell transplantation (HSCT).
      Therefore, we reviewed the data of 1226 patients with acute myelogenous leukemia
      (AML), acute lymphoblastic leukemia (ALL), and chronic myelogenous leukemia (CML)
      who received first allogeneic HSCT between 1994 and 2004, using the database of
      the Kanto Study Group for Cell Therapy (KSGCT), and analyzed the incidence, risk
      factors, and outcome of patients with CNS relapse. Twenty-nine patients developed
      CNS relapse at a median of 296 (9-1677) days after HSCT with a cumulative
      incidence of 2.3%. Independent significant factors associated with CNS relapse
      included ALL as the underlying diagnosis (relative risk [RR] = 9.55, 95%
      confidence interval [CI] = 1.26-72.2, P = .029), nonremission at HSCT (RR = 2.30,
      95% CI = 1.03-5.15, P = .042), the history of CNS invasion before HSCT (RR =
      5.62, 95% CI = 2.62-12.0, P = 9.2 x 10(-6)), and the prophylactic intrathecal
      chemotherapy after HSCT (RR = 2.57, 95% CI = 1.21-5.46, P = .014). The 3-year
      overall survival (OS) after CNS relapse was 18%. In 7 of 29 patients with CNS
      relapse, leukemia was observed only in CNS. Three of 7 patients were alive
      without systemic relapse, resulting in 3-year survival after CNS relapse of 46%.
      Although the outcome of patients with CNS relapse was generally poor, long-term
      disease-free survival could be achieved in some patients.

PMID- 18804040
TI  - Posttransplant autoimmune hemolytic anemia and other autoimmune cytopenias are
      increased in very young infants undergoing unrelated donor umbilical cord blood
      transplantation.
AB  - Autoimmune cytopenias are a recognized complication of hematopoietic stem cell
      transplant (HSCT), and are considered to be a feature of chronic graft-versus
      host disease (cGVHD). We report on a cohort of very young infants (< or =3 months
      of age) receiving HSCT from unrelated donor umbilical cord blood for genetic
      disorders who developed posttransplant autoimmune cytopenias at an increased rate
      compared to older aged controls. These infants received a conditioning regimen
      consisting of busulfan, cyclophosphamide, and antithymocyte globulin (ATG). All
      infants received HLA mismatched unrelated umbilical cord blood as graft source.
      GVHD prophylaxis was either cyclosporine + methylprednisolone (n = 16) or
      cyclosporine + mycophenolate mofetil (n = 3). Engraftment, acute GVHD (aGVHD) and
      cGVHD, survival, treatment-related mortality (TRM), and deaths were evaluated.
      Ten patients developed cGVHD manifesting as autoimmune cytopenias at a median 247
      days posttransplant with a cumulative incidence of 44% (95% confidence interval
      [CI] 21%-68%) and 56% (95% CI 32%-80%) at 1 and 2 years, respectively. In 6 of 10
      patients developing autoimmune cytopenias, cGVHD presented as autoimmune
      cytopenia de novo. The cytopenias observed included anemia (n = 4),
      thrombocytopenia (n = 1), anemia with thrombocytopenia (n = 3), and pancytopenia
      (n = 2). No graft factors were identified as being significant to development of
      cGVHD. All patients responded to treatment with methylprednisolone, azithioprine
      +/- rituximab. One patient required splenectomy. We hypothesize that
      posttransplant immunosuppression interferes with normal immune ontogeny creating
      immune dysregulation and graft directed cell destruction. Alternative strategies
      to prevent GVHD should be considered for this unique patient population.

PMID- 18804042
TI  - Megadose CD34(+) cell grafts improve recovery of T cell engraftment but not B
      cell immunity in patients with severe combined immunodeficiency disease
      undergoing haplocompatible nonmyeloablative transplantation.
AB  - To determine whether T cell engraftment and recovery of B cell immunity could be
      improved, we prospectively treated 15 children with severe combined
      immunodeficiency disease (SCID) with megadoses of haplocompatible CD34(+) cells
      and a fixed number of CD3(+) cells without previous myeloablative chemotherapy.
      Evidence of T cell engraftment was seen in 73% of patients (95% confidence
      interval [CI] = 48%-90%). Engraftment was more likely in patients with X-linked
      SCID and in those with evidence of maternal engraftment at the time of diagnosis.
      In patients with T cell engraftment, the median time to development of a CD4
      count > 200 cells/mm(3) and a phytohemagglutinin response > 50% of control was
      1.2 and 4.9 months, respectively. Clearance of preexisting infections occurred
      after a median of 2.8 months. B cell function developed in 33% of engrafted
      patients (95% CI = 14%-61%). The 1-year event-free survival (EFS) rate was 60%
      (95% CI = 36%-80%), and the overall survival (OS) rate was 87% (95% CI = 61%
      98%), with a median follow-up of 39 months. The use of megadoses of CD34(+) cells
      with a fixed number of CD3(+) cells in nonmyeloablative hematopoietic stem cell
      transplantation (HSCT) in patients with SCID is associated with excellent
      engraftment, T cell recovery, and OS; however, B cell function does not recover
      in most patients.

PMID- 18804041
TI  - Comparison of twin and autologous transplants for multiple myeloma.
AB  - Relapse is the overwhelming cause of treatment failure after autologous
      transplantation for multiple myeloma (MM). For patients with a syngeneic donor,
      twin transplants provide a healthy graft that is free of myeloma. The relative
      impact of the graft on posttransplant relapse can be estimated by comparing risk
      of relapse after hematopoietic cell transplantation from genetically identical
      twins versus autotransplants because confounding differences in minor or major
      histocompatibility antigens are absent in the syngeneic transplant setting.
      Outcomes of 43 subjects who received twin transplants for MM were compared to 170
      matched autotransplant recipients reported to the Center for International Blood
      and Marrow Transplant Research (CIBMTR). Multivariate analysis was performed by
      fitting a Cox model stratified on matched pairs. The matched transplant patients
      studied were similar with respect to subject-, disease-, and transplant-related
      characteristics. Cumulative incidence of relapse/progression was significantly
      lower, and progression-free survival (PFS) was significantly higher following
      twin transplants. In multivariate analysis, the probability of
      relapse/progression was lower in twins (relative risk [RR] = 0.49, 95% confidence
      interval [CI] 0.28-0.86, P = .011). Twin transplants have a significantly lower
      relapse risk than autotransplants in MM, suggesting that graft composition may
      impact outcomes following high-dose chemotherapy.

PMID- 18804043
TI  - Comparable outcomes in nonsecretory and secretory multiple myeloma after
      autologous stem cell transplantation.
AB  - Nonsecretory myeloma (NSM) accounts for <5% of cases of multiple myeloma (MM).
      The outcome of these patients following autologous stem cell transplantation
      (ASCT) has not been evaluated in clinical trials. We compared the outcomes after
      ASCT for patients with NSM reported to the Center for International Blood and
      Marrow Transplant Research (CIBMTR) between 1989 and 2003, to a matched group of
      438 patients (4 controls for each patient) with secretory myeloma (SM). The
      patients were matched using propensity scores calculated using age, Durie-Salmon
      stage, sensitivity to pretransplant therapy, time from diagnosis to transplant,
      and year of transplant. Disease characteristics were similar in both groups at
      diagnosis and at transplant except higher risk of anemia, hypoalbuminemia, and
      marrow plasmacytosis (in SM) and plasmacytoma (more in NSM). Cumulative incidence
      of treatment-related mortality (TRM), relapse, progression-free survival (PFS),
      and overall survival (OS) were similar between the groups. In multivariate
      analysis, based on a Cox model stratified on matched pairs and adjusted for
      covariates not considered in the propensity score, we found no difference in
      outcome between the NSM and SM groups. In this large cohort of patients
      undergoing ASCT, we found no difference in outcomes of patients with NSM compared
      to those with SM.

PMID- 18804044
TI  - HLA-matched sibling hematopoietic stem cell transplantation for fanconi anemia:
      comparison of irradiation and nonirradiation containing conditioning regimens.
AB  - Related to the underlying DNA repair defect that is the hallmark of Fanconi
      anemia (FA), preparatory regimen-related toxicities have been obstacles to
      hematopoietic cell transplantation (HCT). In an attempt to decrease the risk and
      severity of regimen-related toxicities, nonirradiation regimens have been
      explored. The aim of this study is to compare outcomes after irradiation and
      nonirradiation regimens in 148 FA patients and identify risk factors impacting
      upon HCT outcomes. Hematopoietic recovery, acute and chronic graft-versus-host
      disease (aGVHD, GVHD), and mortality were similar after irradiation and
      nonirradiation regimens. In both groups of recipients aged >10 years, prior use
      of androgens and cytomegalovirus seropositivity in either the donor or recipient
      were associated with higher mortality. With median follow-ups >5 years, the 5
      year probability of overall survival, adjusted for factors impacting overall
      mortality was 78% and 81% after irradiation and nonirradiation regimens, P = .61.
      In view of the high risk of cancer and other radiation-related effects on growth
      and development, these results support the use of nonirradiation preparatory
      regimens. As the peak time for developing solid tumors after HCT is 8 to 9 years,
      longer follow-up is required before definitive statements can be made regarding
      the impact of nonirradiation regimens on cancer risk.

PMID- 18804045
TI  - Impact of T cell chimerism on clinical outcome in 117 patients who underwent
      allogeneic stem cell transplantation with a busulfan-containing reduced-intensity
      conditioning regimen.
AB  - Within the concept of reduced-intensity stem cell transplantation (RIST) there is
      a wide range of different regimens used, and little information is available on
      the clinical impact of chimerism status in patients conditioned with a busulfan
      containing regimen. Therefore, we retrospectively reviewed lineage-specific
      chimerism and the subsequent clinical outcome in 117 patients (median age, 55
      years; range: 29-68) who underwent busulfan-containing RIST. The conditioning
      regimen consisted of busulfan (oral 8 mg/kg or i.v. 6.4 mg/kg) and fludarabine
      (180 mg/m(2), n = 64) or cladribine (0.66 mg/kg, n = 53), with or without 2-4 Gy
      total-body irridiation (TBI) (n = 26) or antihuman T-lymphocyte immunoglobulin
      (ATG; 5-10 mg/kg; n = 31). Chimerism was evaluated with peripheral blood samples
      taken on days 30, 60, and 90 after transplantation by polymerase chain reaction
      (PCR)-based amplification of polymorphic short tandem repeat regions. The median
      follow-up of surviving patients was 1039 days (153-2535). The percent donor
      chimerism was significantly higher in granulocyte than T cell fraction throughout
      the entire course, and the median (mean) values were, respectively, 100% (96%)
      versus 95% (83%), 100% (98%) versus 100% (89%), and 100% (98%) versus 100% (91%)
      at days 30, 60, and 90 after RIST. In a multivariate analysis, having received <2
      types of chemotherapy regimens before RIST was the only factor that was
      significantly associated with low donor T cell chimerism (<60%) at day 30 (hazard
      ratio [HR]: 6.1; 95% confidence interval [CI], 2.1-18.4; P < .01). The median
      percentage of donor T cell chimerism at day 30 was 9% (0%-63%) in 5 patients who
      experienced graft failure, which was significantly lower than that (97%; 15%
      100%) in the rest of the patients (P < .01). No correlation was found between the
      kinetics of T cell chimerism and the occurrence of acute or chronic GVHD (aGVHD,
      cGVHD). The stem cell source and the addition of TBI or ATG were not associated
      with the degree of T cell chimerism, overall survival (OS) or event-free survival
      (EFS). In a Cox proportional hazard model, low donor T cell chimerism of <60% at
      day 30 was associated with both poor OS (HR: 2.2; 95% CI, 1.1-4.5; P = .02) and
      EFS (HR: 2.0; 95% CI, 1.1-3.8; P = .02). In conclusion, we found that 43% of the
      patients retained mixed donor T cell chimerism (<90% donor) at day 30, whereas
      92% achieved complete chimerism in granulocyte fraction. Low donor T cell
      chimerism of <60% at day 30 may predict a poor outcome, and a prospective study
      to examine the value of early intervention based on chimerism data is warranted.

PMID- 18804046
TI  - Expansion of cytomegalovirus pp65 and IE-1 specific cytotoxic T lymphocytes for
      cytomegalovirus-specific immunotherapy following allogeneic stem cell
      transplantation.
AB  - Adoptive immunotherapy with antigen-specific cytotoxic T lymphocytes (CTLs) has
      proven effective in restoring cellular immunity to cytomegalovirus (CMV) and
      preventing viral reactivation after allogeneic stem cell transplantation (SCT).
      In an effort to develop a cost-effective, relatively rapid method of CMV CTL
      expansion, we investigated the use of a pool of overlapping CMV peptides. Because
      the possibility exists of vaccinating CMV-seronegative donors, and these
      individuals may have T cell responses predominantly against IE-1, commercially
      available peptide mixes for pp65 as well as IE-1 were used to stimulate CTLs from
      10 seropositive donors. Of these 10 donors, 4 responded to pp65 only, 1 did not
      respond to either pp65 or IE-1, 4 responded to both pp65 and IE-1, and 1
      responded to IE-1 only. These CMV- specific T cells included a mixture of CD4(+)
      and CD8(+) effectors, and specific cytotoxicity correlated with interferon-gamma
      production. The costs associated with a 28-day maintenance course of intravenous
      ganciclovir, cidofovir, foscarnet, and valganciclovir, as well as the preparation
      and shipping a single dose of CTLs, were determined. The price of generating CMV
      CTLs using this method was comparable to or less expensive than a 28-day
      maintenance course for these agents, not including the costs associated with drug
      administration, supportive care, and the treatment of drug-related complications.
      Considering the relative ease, low cost, and the fact that CTL administration can
      result in CMV-specific immune reconstitution, this option should be considered
      for patients with CMV reactivation or for prophylaxis in patients at high risk
      for infection.

PMID- 18804047
TI  - Prognostic factors of chronic graft-versus-host disease following allogeneic
      peripheral blood stem cell transplantation: the national institutes health scale
      plus the type of onset can predict survival rates and the duration of
      immunosuppressive therapy.
AB  - Several grading systems have been developed in the bone marrow transplantation
      setting in attempts to predict survival in patients with chronic graft-versus
      host disease (cGVHD). In this study, we evaluated the prognostic value of the
      National Institutes of Health (NIH) scoring system and investigated for any
      additional prognostic factors in a series of 171 patients undergoing peripheral
      blood stem cell transplantation (PBSCT) from matched related donors. The
      cumulative incidence of cGVHD was 70%; cumulative incidences of mild, moderate,
      and severe cGVHD were 29%, 42% and 28%, respectively. Overall, 68% of patients
      were free from immunosuppression 5 years after transplantation. Absence of
      previous acute GVHD (aGVHD; hazard ratio [HR] = 2; P = .004) and mild cGVHD (HR =
      4.2; P = .007) increased the probability of being off immunosuppressive treatment
      by the last follow-up. Overall survival (OS) at 5 years was 52%. Severe cGVHD,
      according to the NIH scoring system (HR = 13.27; P = .001) adversely influenced
      outcome, whereas de novo onset (HR = 0.094; P = .003) had a more favorable impact
      on survival. The combination of both variables allowed us to identify 4 different
      subgroups of patients with OS of 82%, 70%, 50%, and 25%. Our findings indicate
      that the NIH scoring system has some prognostic value in patients undergoing
      PBSCT and, together with the type of onset, must be considered to predict the
      possible outcome of patients who develop cGVHD.

PMID- 18804048
TI  - Persistence of human parvovirus B19 in multipotent mesenchymal stromal cells
      expressing the erythrocyte P antigen: implications for transplantation.
AB  - Multipotent mesenchymal stromal cells (MSCs) are used to improve the outcome of
      hematopoietic stem cell transplantation (HCST) and in regenerative medicine. MSCs
      may harbor persistent viruses that may compromise their clinical benefit,
      however. Retrospectively screened, 1 of 20 MSCs from healthy donors contained
      parvovirus B19 (B19) DNA. MSCs express the B19 receptor (P antigen/globoside) and
      a co-receptor (Ku 80) and can transmit B19 to bone marrow cells in vitro,
      suggesting that the virus can persist in the marrow stroma of healthy
      individuals. Two patients undergoing HSCT received the B19-positive MSCs as
      treatment for graft-versus-host disease; neither developed viremia nor
      symptomatic B19 infection. These findings demonstrate for the first time that
      persistent B19 in MSCs can infect hematopoietic stem cells and underscore the
      importance of monitoring B19 transmission by MSC products.

PMID- 18804049
TI  - Influence of polymorphism within the heme oxygenase-I promoter on overall
      survival and transplantation-related mortality after allogeneic stem cell
      transplantation.
AB  - Aside from major and minor histocompatibility antigens, genetic polymorphisms of
      various donor and host genes have been found to be risk factors for graft-versus
      host disease and transplantation-related mortality (TRM). The heme oxygenase I
      (HO-I) protein has been implicated in regulating inflammatory response and has
      been described as a "protective gene" in solid organ transplantation. In humans,
      the promoter region displays length polymorphism due to a variable number of GT
      repeats. Individuals exhibiting 29 or fewer GT repeats express higher levels of
      HO-I on cellular stress compared with individuals with 30 or more GT repeats. We
      retrospectively analyzed length polymorphisms of 92 donor-host pairs undergoing
      allogeneic stem cell transplantation. Our findings demonstrate that mainly donor
      polymorphism leading to high expression of HO-1 (<30 GT repeats) on stress
      signals is associated with reduced overall survival, and that TRM is
      significantly increased in this group. This reduction in survival was most
      prominent when unrelated donors were used. Polymorphisms of the recipient HO-1
      genes did not influence posttransplantation outcomes. We conclude that HO-1
      polymorphism represents a new genetic risk factor for TRM and overall survival.

PMID- 18804050
TI  - Ex vivo expansion and Th1/Tc1 maturation of umbilical cord blood T cells by
      CD3/CD28 costimulation.
AB  - One major limitation of UCBT is the lack of donor cells available for
      posttransplantation donor leukocyte infusions (DLI) to boost immunity or induce
      graft-versus-leukemia (GVL) activity. Starting from a approximately 5% fraction
      of a UCB graft, we report the feasibility and biological characteristics of ex
      vivo expansion of frozen/thawed CB T cells by anti-CD3 and anti-CD28 antibody
      coated Dynal beads in the presence of interleukin (IL)-2. We postulated that
      while undergoing expansion, UCB T cells may mature toward a Th1/Tc1 phenotype and
      acquire the potential for cytotoxicity. Whereas an almost 2-log expansion also
      led to the acquisition of IL-12Ralpha and an increase in Th1 characteristics,
      postexpansion lymphocytes produced less interferon-gamma, tumor necrosis factor
      alpha, and granzyme B; stored almost no perforin; and lacked cytotoxicity against
      allogeneic targets. Collectively, these suggest relative safety from
      acute/hyperacute graft-versus-host disease. CD8(+) T cells expanded
      preferentially, whereas a higher rate of apoptosis in CD4(+) T cells also
      promoted an inverted CD4/CD8 ratio. Most expanded T cells retained expression of
      CD27, CD28, and L-selectin but down-regulated CCR-7. In summary, UCB T cell
      proliferation sustained by CD3/CD28 co-stimulatory beads and IL-2 can lead to
      clinically relevant doses of DLI from a very small fraction of the UCB graft,
      although future strategies to reduce apoptosis may enhance their clinical
      potential.

PMID- 18804051
TI  - Oral proliferative verrucous leukoplakia (PVL) in a post-bone marrow transplant
      patient.

PMID- 18804052
TI  - Lactose enhances cellulase production by the filamentous fungus Acremonium
      cellulolyticus.
AB  - Acremonium cellulolyticus is a fungus that produces cellulase and has been
      exploited by enzyme industry. To promote cellulase production by A.
      cellulolyticus strain C-1, we evaluated the effects of the saccharides: Solka
      Floc (cellulose), soluble soybean polysaccharide (SSPS), pullulan, lactose,
      trehalose, sophorose, cellobiose, galactose, sorbose, lactobionic acid, and
      mixtures as carbon sources for cellulase production. Solka Floc with SSPS
      enhanced cellulase production. Lactose as the sole carbon source induced
      cellulase synthesis in this fungus, and the synergistic effects between lactose
      and Solka Floc was observed. Various enzyme activities and the protein
      composition of crude enzyme produced by cultures with or without addition of
      lactose were analyzed. The results showed that lactose addition greatly improves
      the production of various proteins with cellulase activity by A. cellulolyticus.
      To our knowledge, this is the first report on production of cellulases by lactose
      in the A. cellulolyticus.

PMID- 18804053
TI  - Protein engineering on biphenyl dioxygenase for conferring activity to convert 7
      hydroxyflavone and 5,7-dihydroxyflavone (chrysin).
AB  - A central part (amino-acid position 268-397 of 458 amino-acid residues) of the
      biphenyl dioxygenase large (alpha) subunit, BphA1, from Pseudomonas
      pseudoalcaligenes strain KF707 was exchanged with the corresponding part of BphA1
      from another biphenyl-degrading bacterium, Pseudomonas putida strain KF715, to
      construct hybrid BphA1, BphA1 (715-707). When expressed in Escherichia coli
      together with the bphA2A3A4BC genes from strain KF707, this enzyme was shown to
      possess activity for degrading both 1-phenylnaphthalene and 2-phenylnaphthalene.
      Between central parts of BphA1 from strains KF707 and KF715, the difference of
      amino-acid residues resided only in position 324-325. An attempt was made to
      improve the substrate preference of BphA1 by applying random amino-acid
      substitutions at these positions to BphA1 (715-707). After screening the mutant
      library to bioconvert several flavonoids, BphA1 (1-22; T324A and I325L) and BphA1
      (2-2; T324L and I325I) were selected. When expressed in E. coli together with
      bphA2A3A4B from strain KF707, both BphA1 (1-22) and BphA1 (2-2) bioconverted the
      refractory flavonoids, 7-hydroxyflavone and 5,7-dihydroxyflavone (chrysin), which
      were hardly converted by any unmodified and artificially-modified shuffled
      biphenyl dioxygeneses, into their vicinal diol forms, i.e., 2-(2,3
      dihydroxyphenyl)-7-hydroxy-chromen-4-one and 2-(2,3-dihydroxyphenyl)-5,7
      dihydroxy-chromen-4-one, respectively. In addition, trans-chalcone was converted
      into 3-(2,3-dihydroxyphenyl)-1-phenylpropan-1-one and further into 1,3-bis-(2,3
      dihydroxyphenyl)-propan-1-one. The antioxidative activity of these generated
      compounds was markedly higher than that of the original substrates used.

PMID- 18804054
TI  - Biological detoxification of waste house wood hydrolysate using Ureibacillus
      thermosphaericus for bioethanol production.
AB  - Hydrolysates of lignocelluloses hydrolyzed by diluted sulfuric acid contain toxic
      compounds that inhibit ethanol production by Saccharomyces cerevisiae and the
      ethanologenic recombinant Escherichia coli KO11. We investigated the biological
      detoxification of a hydrolysate of waste house wood (WHW) by a thermophilic
      bacterium, Ureibacillus thermosphaericus. When the hydrolysate was treated with
      this bacterium at 50 degrees C for 24 h, the ethanol production rate by S.
      cerevisiae increased markedly and was comparable to that for the hydrolysate
      treated with an excess amount of calcium hydroxide (overliming). Chromatographic
      analysis of synthetic hydrolysates containing furfural or 5-hydroxymethyl
      furfural that are considered to be major toxic compounds in hydrolysates revealed
      that U. thermosphaericus degrades these compounds. In the WHW hydrolysates,
      however, the concentrations of these compounds were not decreased markedly by the
      bacterium. These results suggest that the bacterium degrades minor but more toxic
      compounds or phenolic compounds in the WHW hydrolysates. The combination of
      bacterial and overliming treatments of hydrolysates minimized significantly the
      decrease in ethanol production rate by E. coli KO11 as fermentation proceeded.
      Because the bacterium grows rapidly and does not consume sugars, our biological
      detoxification should be useful for bioethanol production from acid hydrolysates
      of lignocelluloses.

PMID- 18804055
TI  - Applicability of random cloning method to analyze microbial community in full
      scale anaerobic digesters.
AB  - Microbial communities were analyzed in six full-scale anaerobic digesters and a
      lab-scale digester using the random cloning method. The purposes were to confirm
      the applicability, reproducibility, and error range of this method; to discuss
      the difference in the dominant microbes determined by this method in different
      operational conditions of temperature (mesophilic and thermophilic) and substrate
      (garbage, sewage sludge, and livestock waste); and to determine key microbes in
      each digester. Each sample was analyzed in triplicate. In one of the samples, 373
      clones were analyzed to study the composition of microbial community in the
      digester. Time course analysis was conducted from the start-up period for
      approximately one year in one of the digesters. Similar microbial diversity was
      obtained corresponding to the type of substrate change (sewage sludge to
      garbage). Operational taxonomic units (OTUs) closely related to Coprothermobacter
      sp. and unidentified bacterium clones TUG14 and TUG22 disappeared during the
      first 40 d, while OTUs closely related to Bacillus sp. and Clostridium sp.
      increased later. Microbial diversity in digesters is strongly affected by the
      operational conditions, and similar microbial diversity can be obtained in
      triplicate analysis and under similar operational conditions. The present study
      verified the applicability of this method to discuss the overall difference in
      microbial communities.

PMID- 18804056
TI  - CoCl(2) inhibits neural differentiation of retinoic acid-treated embryoid bodies.
AB  - The effects of CoCl(2) on retinoic acid (RA)-treated embryoid bodies (EBs) were
      investigated. Four-day EBs were treated with 5x10(-6) M of RA for 4 d, then
      subjected to attached culturing for 7 d in the presence of CoCl(2) at 0, 20, and
      100 microM. Differentiation into MAP2- and GFAP-immunopositive cells was
      inhibited by CoCl(2) in a dose-dependent manner. Next, RA-treated EBs were
      dissociated into single cells and cultured for 7 d at an initial cell density of
      1x10(3)/cm(2). The number of cells increased in a CoCl(2)-dose dependent fashion.
      In cultures with 100 microM of CoCl(2), more than 90% of the cells were
      immunopositive for nestin and nestin-immunopositive cells formed clusters, while
      there were few cells immunopositive for MAP2 or GFAP. These results suggest that
      CoCl(2) inhibits neural differentiation of RA-treated EB cells and promotes the
      proliferation of nestin-immunopositive cells, i.e., embryonic stem (ES)-derived
      neural stem-like cells.

PMID- 18804057
TI  - Investigations of Saccharothrix algeriensis growth on synthetic media.
AB  - Development of bacterial resistance to antibiotics has lead to investigations of
      rare bacteria, which produce new bioactive molecules. Saccharothrix algriensis
      has been isolated from the desert Maghreb. It produces dithiolopyrrolones, some
      of which were newly identified. In order to optimize and control production of
      dithiolopyrrolones, investigation regarding microorganism metabolism was
      required. Growth on semisynthetic medium containing 2 g x l(-1) of yeast extract
      was complicated because it was performed on several substrates. Moreover, because
      development of this bacterium on minimum medium was difficult, its composition
      was optimized by screening of different compounds led by yeast extract. Uracil
      added to the minimum medium allowed a maximum biomass production of 1.35 g x l(
      1) compared to 0.32 g x l(-1) without uracil. Moreover, nonpolar amino acids and
      trace metal elements stimulated Saccharothrix algeriensis growth.

PMID- 18804058
TI  - A motif detection and classification method for peptide sequences using genetic
      programming.
AB  - An exploration of common rules (property motifs) in amino acid sequences has been
      required for the design of novel sequences and elucidation of the interactions
      between molecules controlled by the structural or physical environment. In the
      present study, we developed a new method to search property motifs that are
      common in peptide sequence data. Our method comprises the following two
      characteristics: (i) the automatic determination of the position and length of
      common property motifs by calculating the physicochemical similarity of amino
      acids, and (ii) the quick and effective exploration of motif candidates that
      discriminates the positives and negatives by the introduction of genetic
      programming (GP). Our method was evaluated by two types of model data sets.
      First, the intentionally buried property motifs were searched in the artificially
      derived peptide data containing intentionally buried property motifs. As a
      result, the expected property motifs were correctly extracted by our algorithm.
      Second, the peptide data that interact with MHC class II molecules were analyzed
      as one of the models of biologically active peptides with buried motifs in
      various lengths. Twofold MHC class II binding peptides were identified with the
      rule using our method, compared to the existing scoring matrix method. In
      conclusion, our GP based motif searching approach enabled to obtain knowledge of
      functional aspects of the peptides without any prior knowledge.

PMID- 18804059
TI  - Enzymatic saccharification of biologically pretreated Pinus densiflora using
      enzymes from brown rot fungi.
AB  - Enzymatic saccharification of lignocellulosic biomass was performed using culture
      filtrates of brown rot fungi including Gloeophyllum sepiarium, Fomitopsis
      pinicola, and Laetiporus sulphureus. Biological treatment with white rot fungi
      was used as pretreatment prior to enzymatic saccharification. Endoglucanase, beta
      glucosidase, xylanase and cellobiohydrolase activities were determined from
      concentrated culture filtrates of the brown rot fungi. L. sulphureus has the
      highest endoglucanase, beta-glucosidase, and xylanase activities, and F. pinicola
      has the highest cellobiohydrolase activity. When enzymes from L. sulphureus were
      used along with the lignocellulosic biomass pretreated with Stereum hirsutum as
      the carbon source, the total sugar yield was 11.36 mg/0.25 g of dry weight
      biomass, with the highest activities of cellulase and hemicellulase. In order to
      increase the sugar yield, the enzymes from L. sulphureus were mixed with those
      from F. pinicola, which showed high cellobiohydrolase activity. This caused an
      increase in the sugar yield from 11.36 mg to 15.22 mg. When temperature was
      increased to 50 degrees C, the total sugar yield increased to 17.74 mg for the
      same reaction time. The crystallinity of lignocellulosic biomass decreased from
      68.4% to 60.2%, when lignocellulosic biomass pretreated with S. hirsutum was
      hydrolyzed using enzymes from L. sulphureus.

PMID- 18804060
TI  - Decrease in antithrombin III fucosylation by expressing GDP-fucose transporter
      siRNA in Chinese hamster ovary cells.
AB  - The full-length cDNA of GDP-fucose transporter (GFT) was cloned from Chinese
      hamster ovary (CHO) 13D-35D cells. The predicted product consisted of 366 amino
      acids with 86% and 92% similarities to human GFT and mouse GFT, respectively.
      When synthetic small interfering RNA (siRNA) against CHO GFT was introduced into
      human antithrombin III (AT-III)-producing recombinant CHO cells, defucosylated AT
      III increased by 30-40% after 3-d incubation. A GFT siRNA expression plasmid was
      also constructed to defucosylate recombinant AT-III. CHO cells, which were
      transfected with the siRNA expression plasmid, showed approximately 75% reduction
      of Golgi-GDP fucose, resulting in 10-40% increase in defucosylated AT-III.

PMID- 18804061
TI  - Novel catalytic activity of nitrile hydratase from Rhodococcus sp. N771.
AB  - Nitrile hydratase (NHase) from Rhodococcus sp. N771 is a non-heme iron enzyme
      catalyzing the hydration of various nitriles to the corresponding amides. We
      report a novel catalytic activity of NHase. When NHase was incubated with an
      large excess of commercially available isovaleronitrile, the charge transfer band
      from the sulfur ligand to the Fe atom shifted from 710 nm to 820 nm, but
      recovered within 4 min. Similar UV-Vis absorption changes were observed after the
      addition of isobutylisonitrile (iBuNC), a major impurity in commercially
      available isovaleronitrile, suggesting that NHase catalyzes the conversion of
      iBuNC to other compounds. The reaction product was identified as isobutylamine
      (iBuNH(2)) by liquid chromatography tandem mass spectrometry. NHase also converts
      t-butylisonitrile and 1,1,3,3,-tetramethylbutylisonitrile to the corresponding
      amines. Kinetic analysis of the conversion of iBuNC to iBuNH(2) showed a K(m)
      value comparable to that for nitriles, while the V(max) value was more than 10(5)
      times smaller than that for methacrylonitrile. This is the first report
      suggesting that NHase is a bifunctional enzyme catalyzing a reaction other than
      the hydration of nitriles.

PMID- 18804062
TI  - Effect of temperature on microbial community of a glucose-degrading methanogenic
      consortium under hyperthermophilic chemostat cultivation.
AB  - We continuously fed an anaerobic chemostat with synthetic wastewater containing
      glucose as the sole source of carbon and energy to study the effects of
      temperature on the microbial community under hyperthermophilic (65-80 degrees C)
      conditions. Methane was produced normally up to 77.5 degrees C at a dilution rate
      of 0.025 d(-1). However, the concentration of microorganisms and the rate of gas
      production decreased with increasing operation temperature. The microbial
      community in the chemostat at various temperatures was analyzed based on the 16S
      rRNA gene using molecular biological techniques including clone library analysis
      and denaturing gradient gel electrophoresis (DGGE). Aceticlastic methanogens
      related to Methanosarcina thermophila were detected at 65 degrees C and
      hydrogenotrophilic methanogens related to Methanothermobacter thermautotrophicus
      were the dominant methanogens between 70 degrees C to 77.5 degrees C. Bacteria
      related to Clostridium stercorarium and Thermoanaerobacter subterraneus comprised
      the dominant glucose-fermenting bacteria at temperatures of 65 degrees C and
      above, respectively. Bacteria related to Thermacetogenium phaeum and to
      Tepidiphilus margaritifer and Petrobacter succinatimandens were the dominant
      acetate-oxidizing bacteria at 70 degrees C and at 75-77.5 degrees C,
      respectively. The results suggested that, at temperatures of 70 degrees C and
      above, methane production via the aceticlastic pathway was negligible and
      indirect methanogenesis from acetate was dominant. Since acetate oxidation is a
      rate limiting step and a higher temperature favors the hydrolysis and acid
      formation, a two stage fermentation process, acidogenic and methanogenic
      fermentation stages operated under different temperatures, should be more
      suitable for the thermophilic anaerobic treatment at temperatures above 65
      degrees C.

PMID- 18804063
TI  - Chemical composition and bioactivity changes in stale rice after fermentation
      with Cordyceps sinensis.
AB  - Stale rice is typically discarded as waste because it has low eating quality as
      well as low nutritional and biofunctional values resulting from long-time
      storage. After solid-state fermentation with Cordyceps sinensis, fermented stale
      rice (FSR) grains contained higher amount of protein, carbohydrate, lipid,
      dietary fibre, vitamin E, beta-glucan, amino acids and ergosterol than non
      fermented stale rice. It also exhibited increased superoxide dismutase activity.
      When mice were administrated with powdered FSR in 1% carboxymethyl cellulose
      sodium salt solution (FSR-CMC-Na), increases in monoamine oxidase B (MAO-B) in
      brain, lipid peroxides (LPOs) in liver, and myocardial lipofuscin related to
      aging were inhibited, while the activity of MAO-B in liver was not significantly
      changed. The results suggest that solid-state fermentation of low-valued or waste
      stale rice could produce an important bioresource to develop bioactive food
      materials.

PMID- 18804064
TI  - Transient gene expression in guard cell chloroplasts of tobacco using ArF excimer
      laser microablation.
AB  - In this paper, we report a novel method for delivering genes into chloroplasts of
      tobacco cells using laser microablation. The plasmid pLD200-GFP was introduced
      into chloroplasts of Nicotiana tabacum cv. Xanthi guard cells and transient GFP
      expression was detected in the chloroplasts after 2-3 d of incubation. The
      technique uses an argon fluoride (ArF) excimer laser to perforate the cell
      surface in a 4 mum(2) area in the presence of plasmid coated gold microparticles.
      Pretreatment of guard cells to promote stomatal closure prior to laser ablation
      resulted in a significant increase in the survival rate of cells and a transient
      expression rate of 2-3% in trial number basis was archived. Our method has unique
      advantages such as avoiding laborious pretreatments that adversely affect cell
      viability and specific delivery of transgenes into a desired cell in complex leaf
      tissue. This technique is a potential tool for cell specific transient gene
      expression studies for elucidation of gene regulation and expression.

PMID- 18804065
TI  - Expression of Rhodococcus opacus alkB genes in anhydrous organic solvents.
AB  - Rhodococcus opacus B-4 is a benzene-tolerant bacterium which was isolated from a
      gasoline-contaminated soil sample. We previously demonstrated that this organism
      was able to survive and exhibit biocatalytic activity in anhydrous organic
      solvents for at least 5 d. In the present study, we cloned the alkB1 and alkB2
      genes encoding alkane hydroxylases from R. opacus B-4. Heterologous expression of
      the alkB1 and alkB2 genes in Escherichia coli JM109 showed that they encode
      functional alkane hydroxylases with a substrate range of C(5)-C(16). Promoters of
      the alkB1 and alkB2 genes, designated P(alkB1) and P(alkB2), respectively, were
      examined for activity in anhydrous bis (2-ethylhexyl) phthalate (BEHP) containing
      C(5)-C(16)n-alkanes. Two recombinant plasmids, pP(alkB1)EGFP and pP(alkB2)EGFP,
      were constructed by inserting the egfp gene downstream of P(alkB1) and P(alkB2),
      respectively and transformed into R. opacus B-4. Resting cells of R. opacus B-4
      (pP(alkB1)EGFP) showed greater levels of EGFP fluorescence in anhydrous BEHP than
      in 0.85% NaCl, when C(8)-C(16)n-alkanes were supplied as an inducer. Furthermore,
      n-alkane inducibility of P(alkB1) activity in anhydrous BEHP was noticeably
      different from that in 0.85% NaCl. This paper presents the first evidence that
      bacteria can express their genes in essentially anhydrous organic solvents.

PMID- 18804066
TI  - High efficiency production of astaxanthin in an airlift photobioreactor.
AB  - In photobioreactors, photosynthetic microorganisms are exposed to certain
      light/dark cycles caused by light intensity distribution and mixing inside the
      photobioreactor. In this study, Haematococcus pluvialis was cultivated in an
      airlift and a bubble column photobioreactor, and the cell growth and astaxanthin
      production were compared to clarify the effects of liquid circulation.

PMID- 18804067
TI  - Temperature dependences of the distribution coefficients of hydrophobic solutes
      onto porous styrene divinylbenzene resin for the eluent with a low methanol
      content.
AB  - The distribution coefficients of four hydrophobic solutes onto a porous styrene
      divinylbenzene resin were measured using methanol-water mixtures with a low
      methanol content as the eluent at various temperatures. The temperature
      dependence of the distribution coefficients indicated that the elution times of
      the solutes were controllable by elevating the temperature even for the eluent
      with a low methanol content.

PMID- 18804068
TI  - Simple enrichment and independent cultures to expand bacterial community analysis
      from Gedongsongo hot spring.
AB  - Denaturing gradient gel electrophoresis was used to identify bacterial
      communities from Gedongsongo hot spring, Indonesia, by culture-independent and 
      dependent procedures. Predominant species were found to be closely related to
      beta-proteobacteria, particularly from genus Ralstonia and Delftia. Other species
      present include alpha- and gamma-proteobacteria and Thermus groups. Some of the
      strains showed unique 16S rDNA sequences.

PMID- 18804069
TI  - Actinomycete bacteria isolated from the sediments at coastal and offshore area of
      Nagasaki Prefecture, Japan: diversity and biological activity.
AB  - About 800 strains of actinomycetes were isolated from marine environments around
      Nagasaki Prefecture, Japan. The isolates were compared with taxa and biological
      activities of their secondary metabolites. It is suggested that a variety of
      actinomycetes are isolated from different marine environments.

PMID- 18804070
TI  - Patterning mechanisms controlling digit development.
AB  - Vertebrate digits are essential structures for movement, feeding and
      communication. Specialized regions of the developing limb bud including the zone
      of polarizing activity (ZPA), the apical ectodermal ridge (AER), and the non
      ridge ectoderm regulate the patterning of digits. Although a series of signaling
      molecules have been characterized as patterning signals from the organizing
      centers, the delicate cellular and molecular mechanisms that interpret how these
      patterning signals control the detailed digit anatomy remain unclear. Recent
      studies from model organisms and human hand malformations provide new insights
      into the mechanisms regulating this process. Here, we review the current
      understanding of the genetic networks governing digit morphogenesis.

PMID- 18804071
TI  - Collagen1alpha1 promoter drives the expression of Cre recombinase in osteoblasts
      of transgenic mice.
AB  - Osteoblasts participate in bone formation, bone mineralization, osteoclast
      differentiation and many pathological processes. To study the function of genes
      in osteoblasts using Cre-LoxP system, we generated a mouse line expressing the
      Cre recombinase under the control of the rat Collagen1alpha1 (Col1alpha1)
      promoter (Col1alpha1-Cre). Two founders were identified by genomic PCR from 16
      offsprings, and the integration efficiency is 12.5%. In order to determine the
      tissue distribution and the activity of Cre recombinase in the transgenic mice,
      the Col1alpha1-Cre transgenic mice were bred with the ROSA26 reporter strain and
      a mouse strain that carries Smad4 conditional alleles (Smad4(Co/Co)). Multiple
      tissue PCR of Col1alpha1-Cre;Smad4(Co/+)mice revealed the restricted Cre activity
      in bone tissues containing osteoblasts and tendon. LacZ staining in the
      Col1alpha1-Cre;ROSA26 double transgenic mice revealed that the Cre recombinase
      began to express in the osteoblasts of calvaria at E14.5. Cre activity was
      observed in the osteoblasts and osteocytes of P10 double transgenic mice. All
      these data indicated that the Col1alpha1-Cre transgenic mice could serve as a
      valuable tool for osteoblast lineage analysis and conditional gene knockout in
      osteoblasts.

PMID- 18804072
TI  - Calcineurin B-like interacting protein kinase OsCIPK23 functions in pollination
      and drought stress responses in rice (Oryza sativa L.).
AB  - Drought is very harmful to grain yield due to its adverse effect on reproduction,
      especially on pollination process in rice. However, the molecular basis of such
      an effect still remains largely unknown. Here, we report the role of a member of
      CBL (Calcineurin B-Like) Interacting Protein Kinase (CIPK) family, OsCIPK23, in
      pollination and stress responses in rice. Molecular analyses revealed that it is
      mainly expressed in pistil and anther but up-regulated by pollination, as well as
      by treatments of various abiotic stresses and phytohormones. RNA interference
      mediated suppression of OsCIPK23 expression significantly reduced seed set and
      conferred a hypersensitive response to drought stress, indicating its possible
      roles in pollination and drought stress. In consistent, overexpression of
      OsCIPK23 induced the expression of several drought tolerance related genes. Taken
      together, these results indicate that OsCIPK23 is a multistress induced gene and
      likely mediates a signaling pathway commonly shared by both pollination and
      drought stress responses in rice.

PMID- 18804073
TI  - DNA sequencing by synthesis with degenerate primers.
AB  - The degenerate primer-based sequencing was developed by a synthesis method (DP
      SBS) for high-throughput DNA sequencing, in which a set of degenerate primers are
      hybridized on the arrayed DNA templates and extended by DNA polymerase on
      microarrays. In this method, a different set of degenerate primers containing a
      given number (n) of degenerate nucleotides at the 3'-ends were annealed to the
      sequenced templates that were immobilized on the solid surface. The nucleotides
      (n+1) on the template sequences were determined by detecting the incorporation of
      fluorescent labeled nucleotides. The fluorescent labeled nucleotide was
      incorporated into the primer in a base-specific manner after the enzymatic primer
      extension reactions and nine-base length were read out accurately. The main
      advantage of the DP-SBS is that the method only uses very conventional
      biochemical reagents and avoids the complicated special chemical reagents for
      removing the labeled nucleotides and reactivating the primer for further
      extension. From the present study, it is found that the DP-SBS method is
      reliable, simple, and cost-effective for laboratory-sequencing a large amount of
      short DNA fragments.

PMID- 18804074
TI  - Novel ACTG1 mutation causing autosomal dominant non-syndromic hearing impairment
      in a Chinese family.
AB  - The gamma-actin (ACTG1) gene is a cytoplasmic nonmuscle actin gene, which encodes
      a major cytoskeletal protein in the sensory hair cells of the cochlea. Mutations
      in ACTG1 were found to cause autosomal dominant, progressive, sensorineural
      hearing loss linked to the DFNA 20/26 locus on chromosome 17q25.3 in European and
      American families, respectively. In this study, a novel missense mutation
      (c.364A>G; p.I122V) co-segregated with the affected individuals in the family and
      did not exist in the unaffected family members and 150 unrelated normal controls.
      The alteration of residue Ile122 was predicted to damage its interaction with
      actin-binding proteins, which may cause disruption of hair cell organization and
      function. These findings strongly suggested that the I122V mutation in ACTG1
      caused autosomal dominant non-syndromic hearing impairment in a Chinese family
      and expanded the spectrum of ACTG1 mutations causing hearing loss.

PMID- 18804075
TI  - Aberrant DNA methylation in 5' regions of DNA methyltransferase genes in aborted
      bovine clones.
AB  - High rate of abortion and developmental abnormalities is thought to be closely
      associated with inefficient epigenetic reprogramming of the transplanted nuclei
      during bovine cloning. It is known that one of the important mechanisms for
      epigenetic reprogramming is DNA methylation. DNA methylation is established and
      maintained by DNA methyltransferases (DNMTs), therefore, it is postulated that
      the inefficient epigenetic reprogramming of transplanted nuclei may be due to
      abnormal expression of DNMTs. Since DNA methylation can strongly inhibit gene
      expression, aberrant DNA methylation of DNMT genes may disturb gene expression.
      But presently, it is not clear whether the methylation abnormality of DNMT genes
      is related to developmental failure of somatic cell nuclear transfer embryos. In
      our study, we analyzed methylation patterns of the 5' regions of four DNMT genes
      including Dnmt3a, Dnmt3b, Dnmt1 and Dnmt2 in four aborted bovine clones. Using
      bisulfite sequencing method, we found that 3 out of 4 aborted bovine clones (AF1,
      AF2 and AF3) showed either hypermethylation or hypomethylation in the 5' regions
      of Dnmt3a and Dnmt3b, indicating that Dnmt3a and Dnmt3b genes are not properly
      reprogrammed. However, the individual AF4 exhibited similar methylation level and
      pattern to age-matched in vitro fertilized (IVF) fetuses. Besides, we found that
      the 5' regions of Dnmt1 and Dnmt2 were nearly completely unmethylated in all
      normal adults, IVF fetuses, sperm and aborted clones. Together, our results
      suggest that the aberrant methylation of Dnmt3a and Dnmt3b 5' regions is probably
      associated with the high abortion of bovine clones.

PMID- 18804076
TI  - Identification of quantitative trait loci for four morphologic traits under water
      stress in rice (Oryza sativa L.).
AB  - Late season drought coinciding with the rice booting to heading stage affects the
      development of plant height, panicle exsertion, and flag leaf size, and causes
      significant yield loss. In this study, a recombinant inbred line population
      derived from a cross between paddy and upland cultivars was used for data
      collection of the morphologic traits under well water and drought stress
      conditions. Drought stress was applied at the stage of panicle initiation in the
      field in 2002 and at the booting stage in PVC pipes in 2003. The data from stress
      conditions and their ratios (trait measured under stress condition/trait measured
      under well water condition) or differences (trait measured under stress condition
      minus trait measured under well water condition) were used for QTL analysis.
      Totally, 17 and 36 QTLs for these traits were identified in 2002 and 2003,
      respectively, which explained a range of 2.58%-29.82% of the phenotypic
      variation. Among them, six QTLs were commonly identified in the two years,
      suggesting that the drought stress in the two years was different. The genetic
      basis of these traits will provide useful information for improving rice late
      season drought resistance, and their application as indirect indices in rice late
      season drought resistance screening was also discussed.

PMID- 18804077
TI  - A disaster averted: a wake-up call for the need for global disaster preparedness.

PMID- 18804078
TI  - Influencing health policy: strategies for nursing education to partner with
      nursing practice.
AB  - Cost, access, and quality have dominated health policy for more than 30 years.
      During that time, the number of health policy analysts and health services
      researchers has grown exponentially; however, health care policy remains a
      mysterious topic for most registered nurses. The foundations for a professional
      understanding of health care policy and policymaking should be well laid in
      formal education and synthesized with practice and work environments. Without
      time to promote synthesis of policy concepts related to the practice environment,
      nurses have no basis for further exploration and may remain naive to the
      influences of policy throughout their career. Practicing nurses, as eyewitnesses
      to the shortcomings of the U.S. health care system, are best suited to inform
      policymakers of needs, unintended consequences, and success stories. This article
      summarizes strategies to promote a partnership between the academy and nursing
      practice.

PMID- 18804079
TI  - The ethics curriculum for doctor of nursing practice programs.
AB  - Ethical questions dealt with by nurses who have Doctor of Nursing Practice (DNP)
      degrees include traditional bioethical questions, but also business and legal
      ethics. Doctorally prepared nurses are increasingly in positions to make ethical
      decisions rather than to respond to decisions made by others. The traditional
      master's-degree advanced practice nursing curriculum does not address the
      extended expertise and decision-making skills needed by DNP practitioners as they
      face these new types of ethical dilemmas. We propose that a curricular framework
      that addresses clinical, research, business, and legal ethics is needed by all
      DNP students.

PMID- 18804080
TI  - Professor in residence program: a nursing faculty practice.
AB  - The Interdisciplinary Health Research Consultant-Professor in Residence Program
      is a partnership between the University of Medicine and Dentistry of New Jersey
      (UMDNJ) School of Nursing (SN), the New Jersey Joanna Briggs Institute (JBI)
      Center for Evidence Based Practice, and Morristown Memorial Hospital/Atlantic
      Health (MMH/AH). It provides MMH with the expert research and evidence-based
      practice (EBP) consultation and affiliation of a UMDNJ-SN faculty member and the
      resources of the New Jersey JBI Center for Evidence Based Practice. For the
      participating SN faculty member, it provides a clinical laboratory to pursue an
      individualized program of scientific research and scholarly publication. This
      research scholar works closely with the MMH/AH to (a) identify and evaluate
      existing mechanisms to support interdisciplinary health research and EBP at MMH;
      (b) develop and implement new mechanisms to support interdisciplinary health
      research and EBP; (c) implement the findings of published research using EBP
      strategies; (d) replicate interdisciplinary research studies; (e) conduct
      original interdisciplinary research studies; (f) seek intra- or extramural
      funding to support interdisciplinary research studies; and (g) support
      requirements for American Nurses' Credentialing Center accreditation for Magnet
      designation. The program has been successful in its first year of implementation.

PMID- 18804081
TI  - A decision algorithm for admitting students to advanced practice programs in
      nursing.
AB  - The academic records of 738 master's-level nursing students were reviewed to
      develop an optimal compound decision rule for selecting candidates who would be
      successful in advanced practice programs. Chi-square analysis was used to
      establish the association between various combinations of independent variables
      and dismissal status. Independent variables included cumulative grade point
      average (CUMGPA), undergraduate nursing grade point average (NSGGPA), and
      Graduate Record Examination (GRE) scores (quantitative and verbal). Results
      indicated that the combination of any two independent variables was as predictive
      of success as was any combination of three independent variables and that the
      combination of a CUMGPA of 3.25 and NSGGPA of 3.0 predicted success in 99% of the
      cases. The addition of the GRE scores added no additional predictive value. On
      the basis of these analyses, we waived the GRE requirement for applicants who met
      the GPA criteria and developed decision rules for admitting those who did not.

PMID- 18804082
TI  - Adult student satisfaction in an accelerated RN-to-BSN program: a follow-up
      study.
AB  - This mixed-method study revealed accelerated RN-to-BSN (bachelor of science in
      nursing) students' levels of satisfaction with a wide range of college services
      in a small university. Building on seminal research on the topic [Boylston, M.
      T., Peters, M. A., & Lacey, M. (2004). Adult student satisfaction in traditional
      and accelerated RN-to-BSN programs. Journal of Professional Nursing, 20, 23-32.],
      the Noel-Levitz Adult Student Priorities Survey (ASPS) and qualitative interview
      data revealed primary factors involved in nontraditional (adult) accelerated RN
      to-BSN student satisfaction. The ASPS assesses both satisfaction with and
      importance of the following factors: academic advising effectiveness, academic
      services, admissions and financial aid effectiveness, campus climate,
      instructional effectiveness, registration effectiveness, safety and security, and
      service excellence. Of these factors, participants considered instructional
      effectiveness and academic advising effectiveness as most important and
      concomitantly gave high satisfaction ratings to each. In contrast, convenience of
      the bookstore, counseling services, vending machines, and computer laboratories
      were given low importance ratings. The participants cited convenience as a strong
      marketing factor. Loss of financial aid or family crisis was given as a reason
      for withdrawal and, for most students, would be the only reason for not
      completing the BSN program. Outcomes of this investigation may guide faculty,
      staff, and administrators in proactively creating an educational environment in
      which a nontraditional student can succeed.

PMID- 18804083
TI  - The development of the Nurse Workplace Scale: self-advocating behaviors and
      beliefs in the professional workplace.
AB  - AIM: This project developed and tested the Nurse Workplace Scale (NWS) using data
      from a random sample of registered nurses in Massachusetts (n = 904). The NWS was
      adapted from an earlier checklist that measured group behaviors and beliefs in
      the workplace of a variety of nurses. BACKGROUND: Nurses have been thought to
      display non-self-advocating behaviors and beliefs that have contributed to
      disempowering their contribution in health care systems, but no tool has been
      available to assist nurse managers or clinical nurse leaders to test outcomes
      that measure progress toward changing these behaviors. METHOD: A cross-validation
      procedure was used to establish the reliability and validity of the NWS to
      measure behaviors in nurses that are counterproductive in the workplace. RESULTS:
      Two components, "internalized sexism" and "minimization of self" behaviors, were
      established. Scores on the scales were shown to vary with the age and practice
      settings of the nurses. CONCLUSIONS: The NWS can be used in professional
      development settings and nurse workplace intervention studies to measure outcomes
      congruent with nurse empowerment.

PMID- 18804084
TI  - Developing an evidence-based curriculum designed to help psychiatric nurses learn
      to use computers and the Internet.
AB  - This article describes the systematic process in which an evidence-based approach
      was used to develop a curriculum designed to support the computer and Internet
      skills of nurses in psychiatric hospitals in Finland. The pressure on
      organizations to have skilled and motivated nurses who use modern information and
      communication technology in health care organizations has increased due to rapid
      technology development at the international and national levels. However, less
      frequently has the development of those computer education curricula been based
      on evidence-based knowledge. First, we identified psychiatric nurses' learning
      experiences and barriers to computer use by examining written essays. Second,
      nurses' computer skills were surveyed. Last, evidence from the literature was
      scrutinized to find effective methods that can be used to teach and learn
      computer use in health care. This information was integrated and used for the
      development process of an education curriculum designed to support nurses'
      computer and Internet skills.

PMID- 18804085
TI  - The usefulness of the Staff-Patient Interaction Response Scale for palliative
      care nursing for measuring the empathetic capacity of nursing students.
AB  - In communicating with patients, especially patients receiving palliative care,
      empathy plays an important role. Little research has as yet been conducted into
      the development of the empathetic capacity of nursing students at various
      educational levels. An instrument that may be suitable for such research is the
      Staff-Patient Interaction Response Scale for Palliative Care Nursing (SPIRS-PCN).
      The purpose of the article is to determine the validity and reliability of the
      SPIRS-PCN, an instrument measuring empathy in palliative care. The criterion
      related validity, homogeneity, and interrater reliability of the SPIRS-PCN were
      determined in nursing students (n = 357) who varied in gender, age, religious
      orientation, educational level, and experience in patient care. The validity of
      the SPIRS-PCN was underlined by identification of differences for religious
      orientation and the amount of experience. The variables gender, age, and
      educational level were not significant in relation to SPIRS-PCN scores. The
      homogeneity (Cronbach's alpha = .80) and interrater reliability (.74) of the
      instrument were adequate. We conclude that validity of the SPIRS-PCN was
      partially supported, whereas reliability was demonstrated. The instrument is
      feasible in educational situations; we recommend further research into the
      instrument's validity, especially in the progression of students' scores during
      the study program.

PMID- 18804086
TI  - The habit of writing.

PMID- 18804087
TI  - A gas chromatographic method for quantification of detergents frequently used in
      membrane protein structural studies.
AB  - A novel and reliable gas chromatography-flame ionization detection (GC-FID)
      method that can separate and quantify detergents frequently used in membrane
      protein structural studies has been developed. Different detergents were
      identified through FID peaks with different retention times. A quadratic
      regression curve was found to fit the integrated FID peak area against different
      detergent concentrations. Detergents can be quantified as low as the nanogram
      level: lauryl-dimethylamine-N-oxide (LDAO), 5 ng; dodecyl maltoside (DDM), 10 ng;
      and dodecyl phosphocholine (DPC), 50 ng. This method can be applied directly to
      measure detergent concentration and molar ratio of membrane protein to detergents
      during membrane protein extraction, purification, concentration, and
      crystallization.

PMID- 18804088
TI  - Previsible silver staining of protein in electrophoresis gels with mass
      spectrometry compatibility.
AB  - A convenient silver staining method for protein in sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE) gels is described. The method is
      previsible, sensitive, and mass spectrometry (MS) compatible. Two visible counter
      ion dyes, ethyl violet (EV) and zincon (ZC), were used in the first staining
      solution with a detection limit of 2 to 8 ng/band in approximately 1h. The dye
      stained gel can be further stained by silver staining, which is based on acidic
      silver staining employing ZC with sodium thiosulfate as silver ion sensitizers.
      Especially, ZC has silver ion reducing power by cleavage of the diazo bond of the
      dye during silver reduction. The second silver staining can be completed in
      approximately 1h with a detection limit of 0.2 ng/band.

PMID- 18804089
TI  - Structural analysis of the glycosylation of gene-activated erythropoietin
      (epoetin delta, Dynepo).
AB  - Recently, a novel recombinant human erythropoietin (epoetin delta, Dynepo) has
      been marketed in the European Union for the treatment of chronic kidney disease,
      cancer patients receiving chemotherapy, and so forth. Epoetin delta is engineered
      in cultures of the human fibrosarcoma cell line HT-1080 by homologous
      recombination and "gene activation." Unlike recombinant erythropoietins produced
      in other mammalian cells, epoetin delta is supposed to have a human-type
      glycosylation profile. However, the isoelectric focusing profile of epoetin delta
      differs from that of endogenous erythropoietin (both urinary and plasmatic). In
      this work, structural and quantitative analysis of the O- and N-glycans of
      epoetin delta was performed and compared with glycosylation from recombinant
      erythropoietin produced in Chinese hamster ovary (CHO) cells. From the
      comparison, significant differences in the sialylation of O-glycans were found.
      Furthermore, the N-glycan analysis indicated a lower heterogeneity from epoetin
      delta when compared with its CHO homologue, being predominantly tetraantennary
      without N-acetyllactosamine repeats in the former. The sialic acid
      characterization revealed the absence of N-glycolylneuraminic acid. The overall
      sugar profiles of both glycoproteins appeared to be significantly different and
      could be useful for maintaining pharmaceutical quality control, detecting the
      misuse of erythropoietin in sports, and establishing new avenues to link
      glycosylation with biological activity of glycoproteins.

PMID- 18804090
TI  - Characterization of a cancer cell line that expresses a splicing variant form of
      53BP1: separation of checkpoint and repair functions in 53BP1.
AB  - 53BP1 plays important roles in checkpoint signaling and repair for DNA double
      strand breaks. We found that a colon cancer cell line, SW48, expressed a splicing
      variant form of 53BP1, which lacks the residues corresponding to exons 10 and 11.
      Activation of ATM and phosphorylation of ATM and ATR targets occurred in SW48
      cells in response to X-irradiation, and these X-ray-induced responses were not
      enhanced by expression of full-length 53BP1 in SW48 cells, indicating that this
      splicing variant fully activates the major checkpoint signaling in SW48 cells. In
      contrast, the expression of full-length 53BP1 in SW48 cells promoted the repair
      of X-ray-induced DNA damage, evidenced by faster disappearance of X-ray-induced
      gamma-H2AX foci, a marker for DNA damage, and less residual chromosomal
      aberrations after X-irradiation. We conclude that the two major roles of 53BP1,
      the checkpoint signaling and repair for DNA damage, can be functionally
      separated.

PMID- 18804091
TI  - Genome-wide analysis of epigenomic alterations in fetal mouse forebrain after
      exposure to low doses of bisphenol A.
AB  - Bisphenol A (BPA) is one of endocrine disrupting chemicals, being distributed
      widely in the environment. We have been studying the low dose effects of BPA on
      murine forebrain development. Here, we have investigated the genome-wide effect
      of maternal exposure to BPA on the epigenome in mouse forebrain at E12.5 and at
      E14.5. We scanned CpG methylation status in 2500 NotI loci, representing 48
      (de)methylated unique loci. Methylation status in most of them was primarily
      developmental stage-dependent. Each of almost all cloned NotI loci was located in
      a CpG island (CGI) adjacent to 5' end of the transcriptional unit. The mRNA
      expression of two functionally related genes changed with development as well as
      the exposure to BPA. In both genes, changes at the transcriptional level
      correlated well with the changes in NotI methylation status. Taken together,
      epigenetic alterations in promoter-associated CGIs after exposure to BPA may
      underlie some effects on brain development.

PMID- 18804092
TI  - Induction of follistatin precedes gastric transformation in gastrin deficient
      mice.
AB  - We previously showed that antral gastric tumors develop in gastrin-deficient
      (Gas(-/-)) mice. Therefore Gas(-/-) mice were studied sequentially over 12 months
      to identify molecular mechanisms underlying gastric transformation. Fundic
      atrophy developed by 9 months in Gas(-/-) mice. Antral mucosal hyperplasia
      developed coincident with the focal loss of TFF1 and Muc5AC. Microarray analysis
      of 12 month Gas(-/-) tumors revealed an increase in follistatin, an activin/BMP
      antagonist. We found that elevated follistatin expression occurred in the
      proliferative neck zone of hyperplastic antrums, in antral tumors of Gas(-/-)
      mice, and also in human gastric cancers. Follistatin induced cyclin D1 and the
      trefoil factors TFF1 and TFF2 in a gastric cancer cell line. We concluded that
      antral hyperplasia in Gas(-/-) mice involves amplification of mucous cell
      lineages due to follistatin, suggesting its role in the development of antral
      gastric tumors.

PMID- 18804093
TI  - Comparative analysis of ESTs in response to drought stress in chickpea (C.
      arietinum L.).
AB  - Chickpea (Cicer arietinum L.) is an important pulse crop grown mainly in the arid
      and semi-arid regions. To identify the water-stress-induced genes, two non
      normalized cDNA libraries were constructed from the seedling leaves of a drought
      tolerant chickpea cultivar under PEG-treated and -nontreated conditions. About
      2500 clones from each library were selected randomly for sequencing analysis.
      Based on IDEG6 online software analysis, 92 genes were differentially expressed,
      and these genes were involved in diverse biological progresses, such as
      metabolism, transcription, signal transduction, protein synthesis and others.
      Most of the up-regulated genes were related to drought tolerance, and the down
      regulated genes were mainly involved in photosynthesis. The differential
      expression patterns of five functional unigenes were confirmed by quantitative
      real-time PCR (qPCR). The results will help in understanding the molecular basis
      of drought tolerance in chickpea.

PMID- 18804094
TI  - Impaired expression and function of group II metabotropic glutamate receptors in
      pilocarpine-treated chronically epileptic rats.
AB  - Group II metabotropic (mGlu II) receptor subtypes mGlu2 and mGlu3 are important
      modulators of synaptic plasticity and glutamate release in the brain.
      Accordingly, several pharmacological ligands have been designed to target these
      receptors for the treatment of neurological disorders characterized by anomalous
      glutamate regulation including epilepsy. In this study, we examine whether the
      expression level and function of mGlu2 and mGlu3 are altered in experimental
      epilepsy by using immunohistochemistry, Western blot analysis, RT-PCR and
      extracellular recordings. A down-regulation of mGlu2/3 protein expression at the
      mossy fiber pathway was associated with a significant reduction in mGlu2/3
      protein expression in the hippocampus and cortex of chronically epileptic rats.
      Moreover, a reduction in mGlu2 and mGlu3 transcripts levels was noticed as early
      as 24 h after pilocarpine-induced status epilepticus (SE) and persisted during
      subsequent "latent" and chronic periods. In addition, a significant impairment of
      mGlu II-mediated depression of field excitatory postsynaptic potentials at mossy
      fiber-CA3 synapses was detected in chronically epileptic rats. Application of
      mGlu II agonists (2S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine (DCG-IV)
      induced a significant reduction of the fEPSP amplitude in control rats, but not
      in chronic epileptic rats. These data indicate a long-lasting impairment of
      mGlu2/3 expression that may contribute to abnormal presynaptic plasticity,
      exaggerate glutamate release and hyperexcitability in temporal lobe epilepsy.

PMID- 18804095
TI  - Ischemic brain cell-derived conditioned medium protects astrocytes against
      ischemia through GDNF/ERK/NF-kB signaling pathway.
AB  - Conditioned medium (CM) collected from cultures of ischemic microglia,
      astrocytes, and neurons were protective to astrocytes under the in vitro ischemic
      condition (deprivation of oxygen, glucose and serum). Molecular and signaling
      pathway(s) responsible for the CMs protective activity were investigated. Results
      showed that CMs from the ischemic microglia (MCM), astrocytes (ACM) and neurons
      (NCM) contained glial cell line-derived neurotrophic factor (GDNF), which
      protects astrocytes against the in vitro ischemia. Expression of extra cellular
      signal-regulated kinase (ERK1/2) and nuclear factor-kappa B (NF-kB) by GDNF led
      to the inhibition of apoptosis of the ischemic astrocytes in a caspase 3
      independent manner. However, CMs- and GDNF-mediated protection of the ischemic
      astrocytes was protein kinase B (Akt) independent. These results provided
      mechanistic data regarding how GDNF- and CMs-mediated protection of the ischemic
      astrocytes is taking place. These observations provide information for the use of
      GDNF and GDNF containing CMs in the control of cerebral ischemia.

PMID- 18804096
TI  - Axl-/- mice have delayed recovery and prolonged axonal damage following cuprizone
      toxicity.
AB  - Activation of the receptor tyrosine kinase Axl recruits signaling molecules that
      regulate cell growth and survival. To evaluate Axl's role in brain during
      cuprizone toxicity, mice were fed cuprizone and evaluated at 3-, 4-, and 6-week
      cuprizone treatment and 3- and 5-week post-cuprizone withdrawal. At 4-week
      cuprizone treatment, the corpora callosa of wildtype (WT) mice had robust Oil Red
      O+ staining indicative of ongoing phagocytosis. Axl-/- mice had minimal Oil Red
      O+ staining, fewer microglia, and significantly more TUNEL+/ASPA+ mature
      oligodendrocytes than the WT. At 6-week cuprizone treatment, there was
      significantly more Oil Red O+ staining in the Axl-/- corpora callosa than in the
      WT indicating a lag in the clearance of cellular and myelin debris. Relative to
      WT mice, there were fewer mature oligodendrocytes and significantly more SMI-32+
      axons at 3-week post-cuprizone withdrawal, indicative of axonal damage in the Axl
      /- corpora callosa. Electron microscopy determined that at 3-week post-cuprizone
      withdrawal the number of dystrophic axons and axons containing autophagosome-like
      vacuoles/mouse was increased in the Axl-/- mice relative to the WT mice. In Axl-/
      corpora callosa, 5-week post-cuprizone withdrawal, the number of mature
      oligodendrocytes was comparable to the WT mice, but axons in the Axl-/- mice were
      SMI-32+, suggesting that Axl-/- mice have delayed clearance of apoptotic
      oligodendrocytes and myelin debris resulting in prolonged axonal damage and
      recovery from cuprizone toxicity.

PMID- 18804097
TI  - Population-based association study and contrasting linkage disequilibrium pattern
      reveal genetic association of SLC6A4 with autism in the Indian population from
      West Bengal.
AB  - Serotoninergic dysfunction is highly implicated in autism. Serotonin transporter
      gene (SLC6A4) that regulates synaptic serotonin level has been investigated as a
      candidate gene for autism, but consensus opinion on possible association is still
      lacking. Converging evidences of platelet-hyperserotoninemia in approximately 25%
      of the patients, betterment of ritualistic behavior on administration of SSRI and
      linkage to chromosome 17q11 harboring SLC6A4, supports the hypothesis that SLC6A4
      polymorphisms may contribute towards autism pathology. Our recent report on 5
      HTTLPR marker represents the first study on genetic association of SLC6A4 with
      autism in the Indian population. Further analysis involving additional markers
      may reinforce the earlier hypothesis. So in the present study, we have
      investigated the association of a VNTR of 17 bp at intron2 (STin2) and an SNP at
      3'UTR (HTT-3'UTR-SNP) of the gene with autism using family and population-based
      approaches. We have genotyped 421 individuals (93 autistic subjects, their
      parents and 160 controls) and consistent with other publications, family-based
      association studies using individual markers (STin2 and HTT-3'UTR-SNP) have not
      revealed any preferential allelic transmission to the probands. However, the
      interesting finding of strong linkage disequilibrium (LD) between the markers and
      significant disease-specific distortion in the distribution of HTT-3'UTR-SNP
      genotypes (T1chi(2)=5.19, P=0.02; OR=2.89, 95% CI=1.13-7.41) and the specific
      haplotypes of the two markers (LRS=11.85, p(c)=0.02), with higher frequencies of
      T/T genotype and 10-T haplotype in autistic cases suggests that either these
      markers or nearby markers of SLC6A4 that are in LD, may pose a risk towards
      autism in the Eastern Indian population.

PMID- 18804098
TI  - Profound hypothermia determines the anticonvulsant and neuroprotective effects of
      swim stress.
AB  - In contrast to most stressors that appear to be proconvulsant in nature, forced
      swimming (or swim stress) produces substantial anticonvulsant effects. Here we
      describe a series of experiments designed to identify the specific factors of
      swim stress (e.g., duration, swimming behavior, water temperature, and frequency
      of exposure) that are essential for the emergence of anticonvulsant effects in
      the rat. Our results revealed that the anticonvulsant effect of swim stress
      against lithium-pilocarpine convulsions occurred only when swim durations were at
      least 5 min in length and in water temperatures of 20 degrees C or less.
      Moreover, this anticonvulsant effect was not associated with habituation even
      after 10 days of repeated swimming. Treatment with lithium-pilocarpine coupled
      with 10 degrees C or 20 degrees C swim stress for 10 min caused pronounced
      hypothermia (10 to 15 degrees C reduction in body temperature) that required at
      least 12 h to return to baseline. One day after seizures were induced, swim
      stressed rats showed significantly fewer degenerating neurons in the hippocampus
      as revealed by Fluoro-Jade B staining. These results suggest that dramatically
      lowered body temperature could be the critical factor that produces the
      anticonvulsive and neuroprotective effects of swim stress.

PMID- 18804100
TI  - 1,5-anhydroglucitol monitoring in diabetes: a mass balance perspective.
AB  - 1,5-anhydroglucitol (AG) is a nonmetabolizable glucose analogue found in plasma
      due to ingestion. The normal steady-state concentration can be dramatically
      decreased by inhibition of tubular reabsorption during periods of hyperglycemia.
      For this reason, monitoring of AG has been plausibly advocated for detection of
      periodic glucosuric hyperglycemia. In this review, we examine the influence of
      variation in factors affecting both steady-state and transient changes in plasma
      AG. Among normals, the lower and upper limits of the plasma AG reference range
      vary by a factor of 5. Using a simplified mass balance model (a single
      compartment model with 3-6x larger-than-plasma volume of distribution),
      reasonable inter-individual variations of ingestion rate, glomerular filtration
      rate and fractional post-filtration reabsorption are each able to account for the
      wide range of normal, steady-state AG concentrations. In monitoring of changes in
      AG, inter-individual variations in the threshold for glucose excretion, volume of
      distribution and glomerular filtration rate are all likely to significantly
      affect correspondence of integral changes in AG to integral
      glucosuria/hyperglycemia. This combination of variables, affecting both steady
      state and transient changes, is significantly confounding with respect to
      interpretation of serial plasma AG concentrations. Resolution of information
      content of AG monitoring is thus largely that of crossing simple characterization
      of deltas [+,0,-] for changes in AG concentration against the information content
      of hemoglobin A1c monitoring. Despite this limitation, AG monitoring can in
      principle provide information about glycemic control in the short term that is
      not apparent through monitoring of hemoglobin A1c alone. However, whether AG
      monitoring can lead to improved outcomes in diabetes management remains to be
      established.

PMID- 18804099
TI  - Differential sensitivity of human glioblastoma LN18 (PTEN-positive) and A172
      (PTEN-negative) cells to Taxol for apoptosis.
AB  - Glioblastoma is the most malignant brain tumor in humans and an average survival
      of glioblastoma patients hardly exceeds 12 months. Taxol is a plant-derived anti
      cancer agent, which has been used in the treatments of many solid tumors.
      Deletion or mutation of phosphatase and tension homolog located on chromosome ten
      (PTEN) occurs in more than 80% of glioblastomas. We examined the sensitivity of
      human glioblastoma LN18 (PTEN-positive) and A172 (PTEN-negative) cells to Taxol
      for induction of apoptosis. Wright staining showed morphological features of
      apoptosis after treatment with different doses of Taxol for 24 h. Significant
      amount of apoptosis occurred in LN18 cells after treatment with 25 nM Taxol,
      while in A172 cells only after treatment with 50 nM Taxol. Western blotting with
      an antibody that could specifically detect activation or phosphorylation of Akt
      (p-Akt) did not show any p-Akt in LN18 cells but an increase in p-Akt in A172
      cells. Activation of Akt in A172 cells could be reversed by pre-treatment of the
      cells with the phosphatidylinositol-3-kinase (PI3K) inhibitor LY294002,
      indicating involvement of PI3K activity in this process. Apoptosis occurred with
      an increase in Bax:Bcl-2 and mitochondrial release of cytochrome c into the
      cytosol leading to activation of mitochondria-dependent caspase cascade. Taxol
      did not cause upregulation of vascular endothelial growth factor (VEGF), a key
      mediator of angiogenesis, in LN18 cells but substantial upregulation of VEGF in
      A172 cells. After treatment with Taxol, increases in p-Akt and VEGF could
      maintain survival and angiogenesis, respectively, in PTEN-negative glioblastoma.
      As a single chemotherapy, Taxol might be more efficacious in PTEN-positive
      glioblastoma than in PTEN-negative glioblastoma. Thus, our study showed
      differential sensitivity of PTEN-positive and PTEN-negative glioblastoma cells to
      Taxol.

PMID- 18804101
TI  - Comparison of CD44 and cytokeratin 20 mRNA in voided urine samples as diagnostic
      tools for bladder cancer.
AB  - OBJECTIVES: We evaluated the diagnostic efficacy of urinary CD44 and cytokeratin
      20 (CK20) mRNA in comparison with voided urine cytology (VUC) for the detection
      of bladder cancer. DESIGN AND METHODS: A total of 136 Egyptian patients provided
      a single voided urine sample for CD44, CK20 mRNA and VUC before cystoscopy. Of
      the 136 cases, 111 were histologically diagnosed as bladder cancer whereas the
      remaining 25 had benign urological disorders. A group of 20 healthy volunteers
      was also included in this study. Voided urine was centrifuged and the urine
      sediment was used for cytology, estimation of CD44 by ELISA and RNA extraction.
      CK20 mRNA was detected by conventional RT-PCR and quantitative real-time RT-PCR.
      RESULTS: The best cutoff values for CD44 and relative CK20 mRNA detected by real
      time RT-PCR were calculated by receiver operating characteristic curve. The
      positivity rates and the mean ranks for CD44 and CK20 mRNA showed significant
      difference among the three investigated groups (p=0.001). Quantitative real-time
      RT-PCR results were comparable to conventional RT-PCR for the detection of CK20
      mRNA. The positivity rate of CD44 was significantly associated with
      schistosomiasis and urine cytology. The overall sensitivity and specificity were
      52.3% and 88.9% for VUC, 63.1% and 88.9% for CD44, and 82.0% and 97.8% for CK20
      mRNA. Combined sensitivity of VUC with CD44 and CK20 mRNA together (95.5%) was
      higher than either the combined sensitivity of VUC with CD44 (78.4%) or with CK20
      mRNA (91.0%) or than that of the biomarker alone. CONCLUSION: Urinary CD44 and
      CK20 mRNA had higher sensitivities compared to VUC. However, when the diagnostic
      efficacy was considered, CK20 mRNA by either conventional RT-PCR or real-time RT
      PCR had the highest sensitivity and specificity compared to CD44 and VUC.

PMID- 18804102
TI  - Comparison of high-pressure liquid chromatography (HPLC) and Griess reagent
      spectroscopic methods for the measurement of nitrate in serum from healthy
      individuals in the Nordic countries.
AB  - OBJECTIVES: Bioavailability of NO can be estimated by measuring the concentration
      of nitrate (NO(3)) in serum. However, the methods used for the measurement NO(3)
      in plasma or serum show a great degree of variation. Therefore, we compared two
      analytical methods for the measurement of NO(3) in serum. DESIGN AND METHODS: The
      concentration of NO(3) in 600 serum samples collected from healthy individuals
      was determined by the HPLC and by the Griess reagent-spectroscopic method.
      RESULTS: The concentration of NO(3) in the samples was 29.4+/-16.1 micromol/L and
      26.2+/-14.0 micromol/L (mean+/-SD) measured by HPLC and Griess reagent
      spectroscopic method respectively (p<0.0001). We detected a significant
      correlation between the two methods (R=0.81, p<0.0001). CONCLUSIONS: A
      significant correlation between the two methods may suggest that either method
      can be used for the measurement of NO(3) in serum, however the Griess reagent
      spectroscopic method measures lower concentrations of NO(3) than the HPLC method.

PMID- 18804103
TI  - Plexin A3 and plexin A4 convey semaphorin signals during facial nerve
      development.
AB  - In vertebrates, class 3 semaphorins (SEMA3) control axon behaviour by binding to
      neuronal cell surface receptors composed of a ligand binding subunit termed
      neuropilin (NRP) and a signal transduction subunit of the A-type plexin family
      (PLXNA). We have determined the requirement for SEMA3/NRP/PLXN signalling in the
      development of the facial nerve, which contains axons from two motor neuron
      populations, branchiomotor and visceromotor neurons. Loss of either SEMA3A/NRP1
      or SEMA3F/NRP2 caused defasciculation and ectopic projection of facial
      branchiomotor axons. In contrast, facial visceromotor axons selectively required
      SEMA3A/NRP1. Thus, the greater superficial petrosal nerve was defasciculated,
      formed ectopic projections and failed to branch in its target area when either
      SEMA3A or NRP1 were lost. To examine which A-type plexin conveyed
      SEMA3/neuropilin signals during facial nerve development, we combined an
      expression analysis with loss of function studies. Even though all four A-type
      plexins were expressed in embryonic motor neurons, PLXNA1 and PLXNA2 were not
      essential for facial nerve development. In contrast, loss of PLXNA4 phenocopied
      the defects of SEMA3A and NRP1 mutants, and loss of PLXNA3 phenocopied the
      defects of SEMA3F and NRP2 mutants. The combined loss of PLXNA3 and PLXNA4
      impaired facial branchiomotor axon guidance more severely than loss of either
      plexin alone, suggesting that SEMA3A and SEMA3F signals, even though both
      essential, are partially redundant.

PMID- 18804104
TI  - WNT5A selectively inhibits mouse ventral prostate development.
AB  - The establishment of prostatic budding patterns occurs early in prostate
      development but mechanisms responsible for this event are poorly understood. We
      investigated the role of WNT5A in patterning prostatic buds as they emerge from
      the fetal mouse urogenital sinus (UGS). Wnt5a mRNA was expressed in UGS
      mesenchyme during budding and was focally up-regulated as buds emerged from the
      anterior, dorsolateral, and ventral UGS regions. We observed abnormal UGS
      morphology and prostatic bud patterns in Wnt5a null male fetuses, demonstrated
      that prostatic bud number was decreased by recombinant mouse WNT5A protein during
      wild type UGS morphogenesis in vitro, and showed that ventral prostate
      development was selectively impaired when these WNT5A-treated UGSs were grafted
      under under kidney capsules of immunodeficient mice and grown for 28 d. Moreover,
      a WNT5A inhibitory antibody, added to UGS organ culture media, rescued prostatic
      budding from inhibition by a ventral prostatic bud inhibitor, 2,3,8,7
      tetrachlorodibenzo-p-dioxin, and restored ventral prostate morphogenesis when
      these tissues were grafted under immunodeficient mouse kidney capsules and grown
      for 28 d. These results suggest that WNT5A participates in prostatic bud
      patterning by restricting mouse ventral prostate development.

PMID- 18804105
TI  - Arachidonic acid promotes FAK activation and migration in MDA-MB-231 breast
      cancer cells.
AB  - Arachidonic acid (AA) is a common dietary n-6 polyunsaturated fatty acid that is
      present in an esterified form in cell membrane phospholipids, and it might be
      present in the extracellular microenvironment. In particular, AA promotes MAPK
      activation and mediates the adhesion of MDA-MB-435 breast cancer cells to type IV
      collagen. However, the signal transduction pathways mediated by AA have not been
      studied in detail. Our results demonstrate that stimulation of MDA-MB-231 breast
      cancer cells with AA promotes an increase in the phoshorylation of Src and FAK,
      as revealed by site-specific antibodies that recognized the phosphorylation state
      of Src at Tyr-418, and of FAK at tyrosine-397 and in vitro kinase assays. In
      addition, AA also induces an increase in the migration of MDA-MB-231 cells. In
      contrast, AA does not induce phosphorylation of FAK and an increase in cell
      migration of non-tumorigenic epithelial cells MCF10A. Inhibition of Gi/Go
      proteins, LOX and Src activity prevent FAK activation and cell migration. In
      conclusion, our results demonstrate, for the first time, that Gi/Go proteins, LOX
      and Src play an important role in FAK activation and cell migration induced by AA
      in MDA-MB-231 breast cancer cells.

PMID- 18804107
TI  - Collagen XVI expression is upregulated in glioblastomas and promotes tumor cell
      adhesion.
AB  - The poor prognosis of glioblastoma patients is related to diffuse brain invasion
      and interaction of tumor cells with extracellular matrices (ECM). We describe
      expression and function of the FACIT-collagen XVI in glioblastomas. We found
      upregulation of collagen XVI mRNA as well as protein in glioblastomas as compared
      to normal cortex. SiRNA knockdown resulted in decreased cell adhesion whereas
      increased adhesion was observed on surfaces coated with collagen XVI. The
      migration of glioblastoma cells on this substrate remained unchanged. Our results
      demonstrate de-novo expression of collagen XVI in glioblastomas as part of the
      tumor specific remodeling of the ECM.

PMID- 18804106
TI  - Glaucoma-associated myocilin: a better understanding but much more to learn.
AB  - Over a decade has passed since myocilin was identified as the first gene linked
      to early and late-onset primary open-angle glaucoma. During this time,
      considerable effort has been put forth to understand the functional role myocilin
      has in normal and glaucomatous eyes. Myocilin is expressed in many ocular and non
      ocular tissues, is found in both intracellular and extracellular spaces, and has
      been linked to elevations in intraocular pressure. Mutations in the myocilin gene
      that have been associated with glaucoma appear to confer a gain-of-functional
      activity rather than loss of function. Unfortunately, what the normal function of
      myocilin is and how alterations in the function can confer a glaucoma phenotype
      have yet to be elucidated. We will review the current understanding of myocilin
      with special emphasis on the structural makeup of the myocilin gene and protein,
      its possible physiological roles internal and external to ocular cells, the
      regulation of intraocular pressure as evidenced through the use of perfusion
      culture systems and animal models, and as a causative agent in some forms of
      glaucoma.

PMID- 18804108
TI  - GO6976 prevents TNF-alpha-induced suppression of adiponectin expression in 3T3-L1
      adipocytes: putative involvement of protein kinase C.
AB  - Adiponectin, one of the adipokines secreted by adipocytes, possesses insulin
      sensitizing and anti-atherosclerotic properties. Tumor necrosis factor-alpha (TNF
      alpha) is known to suppress the expression and secretion of adiponectin in
      adipocytes; however, the underlying mechanism remains poorly understood. Here, we
      demonstrate that GO6976 (a selective inhibitor of conventional protein kinase C
      (PKC)) prevents TNF-alpha-induced suppression of adiponectin secretion and
      expression in fully differentiated 3T3-L1 adipocytes, accompanied by attenuation
      of c-Jun N-terminal kinase (JNK) activation. Additionally, the transcriptional
      activity of peroxisome proliferator-activated receptor-gamma (PPARg) (a strong
      inducer of adiponectin) on the adiponectin promoter was inhibited in a PKC
      isoform-specific manner. These results raise the possibility that PKC is involved
      in TNF-alpha-induced suppression of adiponectin in 3T3-L1 adipocytes.

PMID- 18804109
TI  - Mapping of yeast Rpn4p transactivation domains.
AB  - The 26S proteasome is a multi-subunit protease complex and plays an essential
      role in many basic cellular processes. The abundance of the 26S proteasome is
      controlled by a negative feedback circuit that involves the Rpn4p transcriptional
      activator. To date, the functional regions of Rpn4p are largely unknown. We
      mapped the Rpn4p transactivation domains by deletion analysis. The distal acidic
      domain has stronger transactivation potential than that of the proximal acidic
      domain. However, the N-terminal region, and not the acidic domains of Rpn4p, is
      crucial for Rpn4p function. Within the N-terminus, we mapped a novel
      transactivation domain, which may be regulated by some modification of lysines in
      a proteolysis-independent manner.

PMID- 18804110
TI  - Sargaquinoic acid and sargahydroquinoic acid from Sargassum yezoense stimulate
      adipocyte differentiation through PPARalpha/gamma activation in 3T3-L1 cells.
AB  - We screened active compounds from natural marine products able to increase
      PPARalpha/gamma transcriptional activity. Sargaquinoic acid (SQA) and
      sargahydroquinoic acid (SHQA) from Sargassum yezoense were identified as novel
      PPARalpha/gamma dual agonists. The binding affinity of SQA with PPARgamma was
      higher than that of the specific PPARgamma agonist troglitazone, leading to an
      activation of PPARgamma transcriptional activity. In parallel, treatment of 3T3
      L1 cells with SQA and SHQA led to an increase in adipocyte differentiation and
      increased expression of adipogenic marker genes such as aP2, PPARgamma, resistin,
      adiponectin, C/EBPalpha and Glut4. Collectively, our data suggest that SQA and
      SHQA are novel PPARalpha/gamma dual agonists and may be beneficial for reducing
      insulin resistance through regulation of adipogenesis.

PMID- 18804111
TI  - Extracellular adenosine production by ecto-5'-nucleotidase protects during murine
      hepatic ischemic preconditioning.
AB  - BACKGROUND & AIMS: The liver tolerates ischemia/reperfusion (IR) poorly. The
      discovery of ischemic preconditioning (IP) has raised hopes that natural pathways
      could be activated to increase hepatic resistance to ischemia. However,
      mechanisms of hepatic IP remain largely unknown. Extracellular adenosine has been
      implicated as an innate anti-inflammatory metabolite, particularly during
      ischemia. We investigated whether ecto-5'-nucleotidase (CD73), the "pacemaker"
      enzyme of extracellular adenosine production, is critical for hepatic protection
      by IP. METHODS: Mice were subjected to 4 cycles of portal triad occlusion and
      reperfusion (3 minutes of ischemia/3 minutes of reperfusion) prior to IR or IR
      alone. RESULTS: Hepatic IP was associated with a significant induction of CD73
      transcript and protein. Targeted gene deletion or pharmacologic inhibition of
      CD73 abolished hepatic protection by IP as measured by lactate dehydrogenase,
      aspartate aminotransferase, and alanine aminotransferase serum levels or
      histologic injury. Increases in extracellular adenosine with IP were
      significantly attenuated in cd73-deficient (cd73(-/-)) mice. Reconstitution of
      cd73(-/-) mice with soluble 5'-nucleotidase resulted in complete restoration of
      hepatoprotection by IP, and hepatic injury following ischemia was attenuated by
      treatment of WT mice with soluble 5'-nucleotidase. Mice deficient in CD73 did not
      demonstrate the same degree of IP-dependent inhibition of acute phase complement
      gene expression/activation as did wild-type mice suggesting that extracellular
      adenosine attenuates hepatic IR via complement regulation. CONCLUSIONS:
      Extracellular adenosine production by CD73 mediates protection during murine
      hepatic IP. Use of soluble 5'-nucleotidase may be a potential therapeutic for
      hepatic ischemia.

PMID- 18804112
TI  - Intestinal differentiation in zebrafish requires Cdx1b, a functional equivalent
      of mammalian Cdx2.
AB  - BACKGROUND & AIMS: The ParaHox transcription factor Cdx2 is an essential
      determinant of intestinal phenotype in mammals throughout development,
      influencing gut function, homeostasis, and epithelial barrier integrity. Cdx2
      expression demarcates the zones of intestinal stem cell proliferation in the
      adult gut, with deregulated expression implicated in intestinal metaplasia and
      cancer. However, in vivo analysis of these prospective roles has been limited
      because inactivation of Cdx2 in mice leads to preimplantation embryonic
      lethality. We used the zebrafish, a valuable model for studying gut development,
      to generate a system to further understanding of the role of Cdx2 in normal
      intestinal function and in disease states. METHODS: We isolated and characterized
      the zebrafish cdx1b ortholog and analyzed its function by antisense morpholino
      gene knockdown. RESULTS: We showed that zebrafish Cdx1b replaces the role of Cdx2
      in gut development. Evolutionary studies have indicated that the zebrafish cdx2
      loci were lost following the genome-wide duplication event that occurred in
      teleosts. Zebrafish Cdx1b is expressed exclusively in the developing intestine
      during late embryogenesis and regulates intestinal cell proliferation and
      terminal differentiation. CONCLUSIONS: This work established an in vivo system to
      explore further the activity of Cdx2 in the gut and its impact on processes such
      as inflammation and cancer.

PMID- 18804113
TI  - Characterisation of effector mechanisms at the host:parasite interface during the
      immune response to tissue-dwelling intestinal nematode parasites.
AB  - The protective immune response that develops following infection with many tissue
      dwelling intestinal nematode parasites is characterised by elevations in IL-4 and
      IL-13 and increased numbers of CD4+ T cells, granulocytes and macrophages. These
      cells accumulate at the site of infection and in many cases can mediate
      resistance to these large multicellular pathogens. Recent studies suggest novel
      potential mechanisms mediated by these immune cell populations through their
      differential activation and ability to stimulate production of novel effector
      molecules. These newly discovered protective mechanisms may provide novel
      strategies to develop immunotherapies and vaccines against this group of
      pathogens. In this review, we will examine recent studies elucidating mechanisms
      of host protection against three widely-used experimental murine models of tissue
      dwelling intestinal nematode parasites: Heligmosomoides polygyrus, Trichuris
      muris and Trichinella spiralis.

PMID- 18804114
TI  - Ligand recognition by ActR, a TetR-like regulator of actinorhodin export.
AB  - TetR-like transcriptional repressors interact with small-molecule ligands to
      control many facets of prokaryotic biology, including clinical antibiotic
      resistance. ActR is a TetR-like protein encoded in the biosynthetic gene cluster
      for the antibiotic actinorhodin and controls the expression of two actinorhodin
      exporters. We showed previously that actinorhodin and its precursor 4-dihydro-9
      hydroxy-1-methyl-10-oxo-3-H-naphtho-[2,3-c]-pyran-3-(S)-acetic acid can bind ActR
      and prevent its interaction with DNA. Here, we compare ActR's interaction with
      naturally occurring and synthetic molecules to show that pathway intermediates
      bind to ActR 5- to 10-fold more tightly than actinorhodin itself, consistent with
      our suggestion that they are the biologically relevant triggers for actinorhodin
      export. We also find that the ligand-binding cavity of this protein can
      accommodate a surprisingly large diversity of ligands, many of which can release
      ActR from DNA in vitro and in vivo. These data suggest that the actR locus could
      be activated by, and perhaps adapted to confer resistance to other antibiotics.

PMID- 18804115
TI  - Induction of MuRF1 is essential for TNF-alpha-induced loss of muscle function in
      mice.
AB  - BACKGROUND: Humoral circulating inflammatory cytokines such as tumor necrosis
      factor alpha (TNF-alpha) can impair skeletal muscle contractility. Furthermore,
      TNF-alpha expression correlates with elevated levels of atrogin-like muscle
      specific ubiquitin E3 ligases, which are presumed to mediate muscle protein
      breakdown and atrophy. However, the casual relationships between MuRF1 and TNF
      alpha and their relative contributions to muscle function impairment are not
      known. METHODS: TNF-alpha or saline was injected into either C57Bl6 or MuRF1(-/-)
      mice. After 16-24 h, the expression of MuRF1 in skeletal muscle was quantified by
      quantitative reverse transcription-PCR and Western blot analysis. Muscle function
      was measured in an organ bath. To obtain a broader overview on potential
      alterations, two-dimensional gel electrophoresis was performed. RESULTS: Wild
      type animals injected with TNF-alpha had higher MuRF1 mRNA expression (saline
      versus TNF-alpha: 56.6+/-12.1 versus 133.6+/-30.3 arbitrary units; p<0.05) and
      protein expression (saline versus TNF-alpha: 0.38+/-0.11 versus 1.07+/-0.25
      arbitrary units; p<0.05) as compared to saline-injected littermates. Furthermore,
      TNF-alpha reduced force development at 150 Hz by 25% in C57Bl6 animals (saline
      versus TNF-alpha: 2412+/-120 versus 1799+/-114 g/cm(2); p<0.05), but not in
      MuRF1(-/-) mice (saline versus TNF-alpha: 2424+/-198 versus 2431+/-180 g/cm(2);
      p=NS). Proteome analysis revealed a significant down-regulation of fast skeletal
      muscle troponin T in wild-type animals treated with TNF-alpha as compared to
      MuRF1(-/-) mice that received TNF-alpha. CONCLUSION: The results of this study
      demonstrate for the first time that TNF-alpha-induced reduction in skeletal
      muscle force development depends on the induction of the atrophy-related E3
      ubiquitin ligase MuRF1. A link for the reduction in muscle force may be the TNF
      alpha/MuRF1-mediated down-regulation of fast skeletal muscle troponin T.

PMID- 18804116
TI  - Solution structure of the complex formed between human complement C3d and full
      length complement receptor type 2.
AB  - Complement receptor type 2 (CR2, CD21) is a cell surface protein that links the
      innate and adaptive immune response during the activation of B-cells through its
      binding to C3d, a cleavage fragment of the major complement component C3. The
      extracellular portion of CR2 comprises 15 or 16 short complement regulator (SCR)
      domains in a partially folded-back but flexible structure. Here, the effect of
      C3d binding to CR2 was determined by analytical ultracentrifugation and X-ray
      scattering. The sedimentation coefficient of unbound CR2 is 4.03 S in 50 mM NaCl.
      Because this agrees well with a value of 3.93 S in 137 mM NaCl, the overall CR2
      structure is unaffected by change in ionic strength. Unbound C3d exists in
      monomer-dimer and monomer-trimer equilibria in 50 mM NaCl, but as a monomer only
      in 137 mM NaCl. In c(s) size-distribution analyses, an equimolar mixture of the
      CR2-C3d complex in 50 mM NaCl revealed a single peak shifted to 4.52 S when
      compared to unbound CR2 at 4.03 S to show that the complex had formed. The CR2
      C3d complex in 137 mM NaCl showed two peaks at 2.52 S and 4.07 S to show that
      this had dissociated. Solution structural models for the CR2 SCR-1/2 complex with
      C3d and CR2 SCR-1/15 were superimposed. These gave an average sedimentation
      coefficient of 4.57 S for the complex, in good agreement with the observed value
      of 4.52 S. It is concluded that CR2 does not detectably change conformation when
      C3d is bound to it. Consistent with previous analyses, its C3d complex is not
      formed in physiological salt conditions. The implications of these solution
      results for its immune role are discussed. To our knowledge, this is the first
      solution structural study of a large multidomain SCR protein CR2 bound to its
      physiological ligand C3d.

PMID- 18804117
TI  - Computational redesign of a protein-protein interface for high affinity and
      binding specificity using modular architecture and naturally occurring template
      fragments.
AB  - A new method is presented for the redesign of protein-protein interfaces,
      resulting in specificity of the designed pair while maintaining high affinity.
      The design is based on modular interface architecture and was carried out on the
      interaction between TEM1 beta-lactamase and its inhibitor protein, beta-lactamase
      inhibitor protein. The interface between these two proteins is composed of
      several mostly independent modules. We previously showed that it is possible to
      delete a complete module without affecting the overall structure of the
      interface. Here, we replace a complete module with structure fragments taken from
      nonrelated proteins. Nature-optimized fragments were chosen from 10(7) starting
      templates found in the Protein Data Bank. A procedure was then developed to
      identify sets of interacting template residues with a backbone arrangement
      mimicking the original module. This generated a final list of 361 putative
      replacement modules that were ranked using a novel scoring function based on
      grouped atom-atom contact surface areas. The top-ranked designed complex
      exhibited an affinity of at least the wild-type level and a mode of binding that
      was remarkably specific despite the absence of negative design in the procedure.
      In retrospect, the combined application of three factors led to the success of
      the design approach: utilizing the modular construction of the interface,
      capitalizing on native rather than artificial templates, and ranking with an
      accurate atom-atom contact surface scoring function.

PMID- 18804118
TI  - Is the genotoxic effect of magnetic resonance negligible? Low persistence of
      micronucleus frequency in lymphocytes of individuals after cardiac scan.
AB  - Magnetic resonance imaging is a diagnostic technique widely used in medicine and
      showing a growing impact in cardiology. Biological effects associated to magnetic
      resonance electromagnetic fields have received far little attention, but it
      cannot be ruled out that these fields can alter DNA structure. The present study
      aimed at to identify possible DNA damage induced by magnetic resonance scan in
      humans. Lymphocyte cultures from healthy subjects had been exposed into magnetic
      resonance device for different times and under different variable magnetic
      exposure in order to build dose-effect curves, using micronuclei induction as
      biological marker. Replicate cultures were also left for 24h at room temperature
      before stimulation, to verify possible damage recovery. Furthermore, micronuclei
      induction and recovery up to 120h have been also evaluated in circulating
      lymphocytes of individuals after cardiac scan. A dose-dependent increase of
      micronuclei frequency was observed in vitro. However after 24h, the frequency
      returns to control value when the exposure is within diagnostic dosage. After in
      vivo scan, a significant increase in micronuclei is found till 24h, after the
      frequencies slowly return to control value.

PMID- 18804119
TI  - Excitatory actions of peptide histidine isoleucine on thalamic relay neurons.
AB  - Peptide histidine isoleucine (PHI) and vasoactive intestinal peptide (VIP) are
      neuropeptides synthesized from a common precursor, prepro-VIP, and share
      structural similarity and biological functions in many systems. Within the
      central nervous system and peripheral tissues, PHI and VIP have overlapping
      distribution. PHI-mediated functions are generally via activation of VIP
      receptors; however, the potency and affinity of PHI for VIP receptors are
      significantly lower than VIP. In addition, several studies suggest distinct PHI
      receptors that are independent of VIP receptors. PHI receptors have been cloned
      and characterized in fish, but their existence in mammals is still unknown. This
      study focuses on the functional role of PHI in the thalamus because of the
      localization of both PHI and VIP receptors in this brain region. Using
      extracellular multiple-unit recording techniques, we found that PHI strongly
      attenuated the slow intrathalamic rhythmic activity. Using intracellular
      recording techniques, we found that PHI selectively depolarized thalamic relay
      neurons via an enhancement of the hyperpolarization-activated mixed cation
      current, Ih. Further, the actions of PHI were occluded by VIP and dopamine,
      indicating these modulators converge onto a common mechanism. In contrast to
      previous work, we found that PHI was more potent than VIP in producing excitatory
      actions on thalamic neurons. We next used the transgenic mice lacking a specific
      VIP receptor, VPAC2, to identify its possible role in PHI-mediated actions in the
      thalamus. PHI depolarized all relay neurons tested from wild-type mice
      (VPAC2(+/+)); however, in knockout mice (VPAC2(-/-)), PHI produced no change in
      membrane potential in all neurons tested. Our findings indicate that excitatory
      actions of PHI are mediated by VPAC2 receptors, not by its own PHI receptors and
      the excitatory actions of PHI clearly attenuate intrathalamic rhythmic
      activities, and likely influence information transfer through thalamocortical
      circuits.

PMID- 18804120
TI  - Nociceptin produces antinociception after spinal administration in amphibians.
AB  - Nociceptin, also known as orphanin FQ, is a opioid-like neuropeptide that
      mediates its effects at the nociceptin receptor, a member of the G protein
      coupled receptor superfamily. In mammals, nociceptin produces analgesia after
      spinal administration, however the role of nociceptin and nociceptin receptors in
      the modulation of noxious stimuli in non-mammalian species has not been examined.
      In an amphibian pain model using the acetic acid test with Rana pipiens,
      nociceptin and nociceptin1-13 amide produced dose-dependent antinociception (1
      100 nmol), blocked by the nociceptin antagonist, [Nphe1]-nociceptin1-13 amide (30
      nmol), but not the opioid antagonist, naltrexone (100 nmol/g, s.c.). Conversely,
      the antinociceptive effects of micro, delta, and kappa opioid receptor agonists
      were not blocked by the nociceptin antagonist. Nociceptin and nociceptin1-13
      amide were the least potent of the opioid agonists tested. These studies
      demonstrate that spinal nociceptin receptors and not opioid receptors mediate the
      antinociceptive effect of nociceptin. Considered with previous findings, these
      behavioral data supports a role for nociceptin inhibition of spinal nociception
      in amphibians and perhaps all vertebrates.

PMID- 18804121
TI  - NADPH oxidases in the vasculature: molecular features, roles in disease and
      pharmacological inhibition.
AB  - Until the 1970s, reactive oxygen species (ROS) were considered merely harmful by
      products of aerobic respiration and the driving force behind the evolution of an
      array of cellular antioxidant enzymes with the purpose of rapidly metabolising
      ROS to minimise their oxidising effects. However, the perception that ROS are
      only harmful to cells has since been questioned by a burgeoning body of evidence
      pointing to the existence of enzymes with the dedicated function of generating
      ROS. NADPH oxidases represent the only known family of enzymes whose sole purpose
      is to generate ROS. Members of this enzyme family are expressed across mammalian
      and non-mammalian cells, and influence a multitude of biological functions
      including host defence and redox signalling. However, although ROS are
      deliberately generated by NADPH oxidases during normal cell physiology, the
      observations that their expression and activity is markedly upregulated in the
      blood vessel wall in a number of cardiovascular 'high-risk' states (e.g.
      hypertension, hypercholesterolemia) implicates them in the oxidative stress that
      gives rise to artery disease and ultimately heart attacks and strokes. These
      observations highlight the fact that NADPH oxidases are important therapeutic
      targets in cardiovascular disease and that, hence, there is clearly a need for
      the development of selective inhibitors of these enzymes. Here we highlight the
      structural and biochemical characteristics of the NADPH oxidase family and then
      comprehensively review the literature on the currently available pharmacological
      inhibitors of these enzymes with a particular emphasis on their mechanisms of
      action, isoform selectivity and therapeutic potential in cardiovascular disease.

PMID- 18804122
TI  - AT2 receptors: functional relevance in cardiovascular disease.
AB  - The renin angiotensin system (RAS) is intricately involved in normal
      cardiovascular homeostasis. Excessive stimulation by the octapeptide angiotensin
      II contributes to a range of cardiovascular pathologies and diseases via
      angiotensin type 1 receptor (AT1R) activation. On the other hand, tElsevier
      Inc.he angiotensin type 2 receptor (AT2R) is thought to counter-regulate AT1R
      function. In this review, we describe the enhanced expression and function of
      AT2R in various cardiovascular disease settings. In addition, we illustrate that
      the RAS consists of a family of angiotensin peptides that exert cardiovascular
      effects that are often distinct from those of Ang II. During cardiovascular
      disease, there is likely to be an increased functional importance of AT2R,
      stimulated by Ang II, or even shorter angiotensin peptide fragments, to limit
      AT1R-mediated overactivity and cardiovascular pathologies.

PMID- 18804123
TI  - Top-down attentional control in spatially coincident stimuli enhances activity in
      both task-relevant and task-irrelevant regions of cortex.
AB  - Models of selective attention predict that focused attention to spatially
      contiguous stimuli may result in enhanced activity in areas of cortex specialized
      for processing task-relevant and task-irrelevant information. We examined this
      hypothesis by localizing color-sensitive areas (CSA) and word and letter
      sensitive areas of cortex and then examining modulation of these regions during
      performance of a modified version of the Stroop task in which target and
      distractors are spatially coincident. We report that only the incongruent
      condition with the highest cognitive demand showed increased activity in CSA
      relative to other conditions, indicating an attentional enhancement in target
      processing areas. We also found an enhancement of activity in one region
      sensitive to word/letter processing during the most cognitively demanding
      incongruent condition indicating greater processing of the distractor dimension.
      Correlations with performance revealed that top-down modulation during the task
      was critical for effective filtering of irrelevant information in conflict
      conditions. These results support predictions made by models of selective
      attention and suggest an important mechanism of top-down attentional control in
      spatially contiguous stimuli.

PMID- 18804124
TI  - Molecular cloning and characterization of Ac-TMP-2, a tissue inhibitor of
      metalloproteinase secreted by adult Ancylostoma caninum.
AB  - Ac-TMP-2, an immunodominant hookworm antigen encoding a tissue inhibitor of
      metalloproteinase (TIMP) was cloned by immunoscreening an Ancylostoma caninum
      larval cDNA library with sera pooled from dogs immunized with irradiated A.
      caninum third stage larvae (ir-L3). The open reading frame of Ac-tmp-2 cDNA
      encoded a 244 amino acids (predicted molecular weight of 27.7 kDa), which shared
      a common N-terminus with other vertebrate and invertebrate TIMPs, including Ac
      TMP-1, the most abundant adult hookworm secreted protein. However Ac-TMP-2 also
      contains an unusual multicopy (ten) repeat of the amino acid sequence, KTVEENDE.
      By immunoblotting, Ac-TMP-2 was detected only in adult hookworms and their
      excretory secretory products although the corresponding mRNA was also detected in
      L3. Immunolocalization with specific antiserum showed that native Ac-TMP-2 was
      located in adult worm's esophagus and cephalic glands. Recombinant Ac-TMP-2
      expressed in bacteria was highly immunogenic and recognized by ir-L3 immunized
      dog immune sera. The recombinant Ac-TMP-2 protein inhibited the human matrix
      metalloproteinases, MMP-2, MMP-7 and MMP-13. As an immunodominant protein having
      a possible role in the parasite-host relationship of canine hookworm infection,
      recombinant Ac-TMP-2 represents a plausible target for vaccine development.

PMID- 18804125
TI  - Inflammatory pathways in malaria infection: TLRs share the stage with other
      components of innate immunity.
AB  - Severe forms of malaria infection claim over 1 million lives annually. One aspect
      of severe malaria pathogenesis is an excessive or dysregulated inflammatory
      response to infection. With the characterization of Toll-like receptors (TLRs),
      which initiate inflammation upon detection of microbial products, involvement of
      TLRs in the host response to malaria has undergone intense investigation. While
      TLRs appear to mediate inflammation in malaria infection and may contribute to
      development of severe malaria, it is unlikely that they operate in isolation from
      other components of innate immunity. Here, we highlight recent findings
      implicating other innate immune mechanisms in the host inflammatory response to
      malaria, propose how they may integrate and synergize with TLR pathways, and
      discuss opportunities and challenges associated with anti-inflammatory adjunctive
      therapy for the treatment of severe malaria.

PMID- 18804126
TI  - A rapid serological assay for prediction of Salmonella infection status in
      slaughter pigs using surface plasmon resonance.
AB  - We present a rapid surface plasmon resonance-based serological assay for the
      detection of Salmonella Typhimurium infection in pigs using the Plasmonic((R))
      SPR device. Lipopolysaccharide (LPS, 10 microg mL(-1)) from Salmonella
      Typhimurium was immobilised by self-assembly on a hydrophobic SPR chip. Using
      this LPS-coated chip, it was possible to bind and detect the anti-Salmonella
      Typhimurium antibodies in serum of pigs infected with the bacteria. The developed
      SPR assay is able to differentiate between sera obtained from pigs having low,
      medium, and high levels of Salmonella infection. A commercial ELISA kit was used
      to classify the sera for levels of Salmonella infection on the basis of optical
      density (OD%). A strong positive correlation was observed between the SPR-based
      assay and the ELISA (n=38, r=0.90, p<0.01). The sensitivity and specificity of
      the assay are 0.93 and 0.87, respectively. The SPR-based assay is label-free and
      does not require any sample preparation or dilution steps. The total analysis
      time is 45 min for each serum sample. The assay was found to be specific for
      Salmonella Typhimurium and shows no cross-reactivity to Salmonella Choleraesuis
      or Escherichia coli antibodies. As no sample preparation is required the
      developed assay has the potential to be used as a reliable tool for Salmonella
      monitoring programmes in pork production.

PMID- 18804127
TI  - A new method to determine temporal variability in the period of pre-movement
      electroencephalographic activity.
AB  - The readiness potential (RP), a slow electroencephalographic (EEG) pre-movement
      potential, was used in earlier studies to determine the onset and order of neural
      processes preceding voluntary movement. Latencies in these studies were always
      calculated from the averaged RP, whereas onset times of individual trials
      remained inaccessible. The aim of this study was to use a different, statistical
      approach to examine how variable the onset of single-trial RPs within subjects
      is. We recorded RPs in 15 right-handed healthy subjects while they made self
      paced repetitive unilateral button presses with their dominant right hand.
      Skewness, a measure of distribution asymmetry, was analysed in sets of single
      trial RPs to discriminate between fixed onset and variable onset models. Results
      show that skewness has values around zero across all electrodes and pre-movement
      intervals without any significant deviation. This result obtained for the
      original data was replicated using modelled data with fixed onset times, whereas
      alternative models with variable onset times (i.e., including trials with
      exceptionally early onset) showed significant deviations of skewness from zero.
      In conclusion, for simple repetitive movements with the dominant hand these
      results confirm a fixed onset model of the RP with similar onset times of pre
      movement cortical activation across trials. The methodology might be also
      applicable for other paradigms to test basic assumptions of mental chronometry.

PMID- 18804128
TI  - Usefulness of colon targeted DHA and EPA as novel diabetes medications that
      promote intrinsic GLP-1 secretion.
AB  - Glucagon-like peptide-1 (GLP-1) is a gut-derived peptide secreted from intestinal
      L-cells and now considered as an ideal diabetic medicine. Recently, it was
      reported that the unsaturated fatty acid alpha-linoleic acid promotes the
      secretion of GLP-1 via a G protein-coupled receptor, GPR120. However, the effects
      of long-chain polyunsaturated fatty acids on the secretion of GLP-1 have not been
      examined in vivo. The aim of this study was to evaluate the effects of the long
      chain polyunsaturated fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic
      acid (EPA) on blood glucose levels, plasma insulin, and GLP-1 concentrations. In
      addition, site-specific differences in these effects were determined using
      several intestinal segments: stomach, jejunum, and colon. After an
      intraperitoneal glucose administration (1.5 mg/g weight), each mouse was
      administered vehicle or an alpha-linoleic acid, DHA, EPA or EPA ester (EPA-E)
      solution to each intestinal segment. After an intraperitoneal glucose challenge,
      marked endogenous GLP-1 secretion, substantial insulin release and subsequent
      glucose reductions were observed in the intracolonic DHA and EPA treatment
      groups. In contrast, DHA and EPA did not increase GLP-1 secretion when given in
      the other segments. These data suggested that the colon-specific delivery of DHA,
      EPA, and possibly EPA-E would be a novel antidiabetic treatment by the
      stimulation of intrinsic GLP-1 secretion.

PMID- 18804129
TI  - Low-carbohydrate weight-loss diets. Effects on cognition and mood.
AB  - To examine how a low-carbohydrate diet affects cognitive performance, women
      participated in one of two weight-loss diet regimens. Participants self-selected
      a low-carbohydrate (n=9) or a reduced-calorie balanced diet similar to that
      recommended by the American Dietetic Association (ADA diet) (n=10). Seventy-two
      hours before beginning their diets and then 48 h, 1, 2, and 3 weeks after
      starting, participants completed a battery of cognitive tasks assessing
      visuospatial memory, vigilance attention, memory span, a food-related paired
      associates a food Stroop, and the Profile of Moods Scale (POMS) to assess
      subjective mood. Results showed that during complete withdrawal of dietary
      carbohydrate, low-carbohydrate dieters performed worse on memory-based tasks than
      ADA dieters. These impairments were ameliorated after reintroduction of
      carbohydrates. Low-carbohydrate dieters reported less confusion (POMS) and
      responded faster during an attention vigilance task (CPT) than ADA dieters.
      Hunger ratings did not differ between the two diet conditions. The present data
      show memory impairments during low-carbohydrate diets at a point when available
      glycogen stores would be at their lowest. A commonly held explanation based on
      preoccupation with food would not account for these findings. The results also
      suggest better vigilance attention and reduced self-reported confusion while on
      the low-carbohydrate diet, although not tied to a specific time point during the
      diet. Taken together the results suggest that weight-loss diet regimens
      differentially impact cognitive behavior.

PMID- 18804130
TI  - Biosynthesis and secretion of salusin-alpha from human cells.
AB  - Salusins originally identified using bioinformatics analyses have been shown to
      act on the cardiovascular and endocrine systems. Although the hypotensive
      activity of salusin-alpha is limited, it exerts a significant anti
      atherosclerotic effect via suppression of foam cell formation in human monocyte
      derived macrophages by down-regulating acyl-CoA:cholesterol acyltransferase-1.
      Furthermore, serum salusin-alpha levels show a close negative correlation with
      the severity of atherosclerotic diseases. However, biosynthesis and secretion of
      salusin-alpha peptide from cultured mammalian cells have not been demonstrated to
      date. We examined the expression, synthesis and release of salusin-alpha in human
      derived cell lines. Preprosalusin mRNA and protein were detected ubiquitously in
      all cells tested, whereas the processing of preprosalusin into salusin-alpha
      peptide is dependent upon each cell type. Immunohistochemical study revealed the
      most abundant salusin-alpha-like immunoreactivity to be present in HeLa cells
      which released salusin-alpha-like immunoreactivity into the culture supernatant.
      Analysis of extracted conditioned media from HeLa cells by reverse-phase high
      performance liquid chromatography coupled with radioimmunoassay detection
      revealed a single immunoreactive component that co-eluted with authentic salusin
      alpha. These results present the first evidence that salusin-alpha is
      biosynthesized and released from human-derived cells.

PMID- 18804131
TI  - Cross-clade protective immunity of H5N1 influenza vaccines in a mouse model.
AB  - H5N1 highly pathogenic avian influenza viruses evolved into several clades,
      leading to appreciably distinct antigenicities of their hemagglutinins. As such,
      candidate H5N1 pre-pandemic vaccines for human use should be sought. Here, to
      evaluate fundamental immunogenic variations between H5N1 vaccines, we prepared
      four inactivated H5N1 test vaccines from different phylogenetic clades (clade 1,
      2.1, 2.2, and 2.3.4) in accordance with the WHO recommendation, and tested their
      cross-clade immunity in a mouse model by vaccination followed by challenge with
      heterologous virulent viruses. All H5N1 vaccines tested provided full or partial
      cross-clade protective immunity, except one clade 2.2-based vaccine, which did
      not protect mice from clade 2.3.4 virus challenge. Among the test vaccines, a
      clade 2.1-based vaccine possessed the broadest-spectrum cross-immunity. These
      results suggest that currently stockpiled pre-pandemic vaccines, especially clade
      2.1-based vaccines, will likely be useful as backup vaccines in a pandemic
      situation, even one involving antigenic-drifted viruses.

PMID- 18804132
TI  - Effect of pre-existing anti-tick-borne encephalitis virus immunity on
      neutralising antibody response to the Vero cell-derived, inactivated Japanese
      encephalitis virus vaccine candidate IC51.
AB  - Japanese encephalitis virus (JEV) is the leading cause of viral encephalitis in
      Asia with a case fatality rate up to 35% and long-term sequelae up to 75%. This
      active-controlled, randomized, multi-centre, observer-blind, phase III trial
      investigated the neutralising antibody response to the new Japanese encephalitis
      (JE) vaccine IC51 in subjects with (N=81) and without (N=339) pre-existing tick
      borne encephalitis (TBE) vaccine induced antibodies as determined by TBE enzyme
      linked immunosorbent assay IgG (ELISA). Neutralising antibody response was
      statistically superior in TBE ELISA-positive subjects compared to TBE ELISA
      negative subjects after the first (p<0.0001) but not after the second vaccination
      with IC51. Thus, pre-existing vaccine-induced TBE immunity enhances the
      neutralising JEV-specific antibody response after a single IC51 vaccination.

PMID- 18804133
TI  - Influenza immunization of Dutch general practitioners: vaccination rate and
      attitudes towards vaccination.
AB  - With effect from the 2008/2009 season, yearly influenza immunization will be
      recommended to all Dutch general practitioners (GPs). For successful
      implementation of this recommendation, knowledge about the current vaccination
      rate and attitudes towards vaccination is necessary. In February 2008, a
      questionnaire was mailed to a random sample (n=730) of practicing GPs.
      Vaccination rate was determined and the factors associated with not being
      vaccinated were assessed using multivariate logistic regression. Reasons for
      being vaccinated or not were also recorded. Of the 730 questionnaires sent out,
      698 (96%) were completed and returned. In total, 248 GPs (36%) had been immunized
      against influenza. Independent factors related to not being vaccinated were
      female gender and age <40 years. Having no medical indication for an influenza
      vaccination and the conviction that one is protected against influenza because of
      frequent professional exposure to the virus were the most frequently reported
      reasons for not being vaccinated. The most frequently reported motives for being
      vaccinated were personal protection against influenza and a lower risk of
      transmitting the virus to patients. Education of GPs about the effects of
      vaccination may be needed to ensure their compliance to the current
      recommendation of yearly influenza immunization.

PMID- 18804134
TI  - MeNZB vaccine and epidemic control: when do you stop vaccinating?
AB  - New Zealand developed a strain-specific group B meningococcal vaccine to control
      an epidemic. Following a mass vaccination campaign of three doses to the
      population under 20 years of age, commencing in July 2004, the vaccine continued
      to be offered routinely as a four-dose schedule from 6 weeks of age. There is
      little international data on when to cease epidemic vaccination campaigns. The
      decision to stop using this vaccine needed to take into account a range of
      factors. These included epidemiology, vaccine effectiveness and duration of
      immunity, vaccine coverage, concomitant use with other vaccinations being added
      to the infant schedule, vaccine supply and cost-benefit criteria. This paper
      discusses these issues, along with the potential challenges for communication to
      both health professionals and the public.

PMID- 18804135
TI  - Production, quality control, stability and pharmacotoxicity of cGMP-produced
      Plasmodium falciparum AMA1 FVO strain ectodomain expressed in Pichia pastoris.
AB  - Plasmodium falciparum apical membrane antigen 1 (PfAMA1) is a leading asexual
      blood stage vaccine candidate for malaria. In preparation for clinical trials,
      PfAMA1 ectodomain (amino acid 25-545, FVO strain) was produced in Pichia pastoris
      by 35L scale fed batch fermentation under current Good Manufacturing Practice
      (cGMP). Fermentation was followed by a three-step chromatographic purification
      procedure resulting in a yield of 5.8g of purified protein. As judged by size
      exclusion chromatography, the cGMP-product comprised >95% PfAMA1 monomer, the
      remainder being predominantly PfAMA1 dimer. In SDS-PAGE two main bands of 68 and
      70kDa and some minor bands were evident. Under reducing conditions a site of
      limited proteolytic cleavage within a disulphide bonded region became evident;
      less than 15% of the protein had this internal cleavage. By mass-spectrometric
      analysis, all bands analyzed in overloaded SDS-PAGE gels comprised PfAMA1 derived
      products. The protein was quantitatively bound by immobilized 4G2, a monoclonal
      antibody reactive with a reduction sensitive conformational determinant. The
      lyophilized product was stable for over 1 year. Immunopotency did not diminish,
      and storage did not lead to alterations in the behaviour of the protein upon
      formulation with adjuvants selected for Phase I clinical evaluation. These
      formulations also showed no pharmacotoxicity in rabbits. The final product
      conformed to preset criteria and was judged suitable for use in human clinical
      trials.

PMID- 18804136
TI  - First administration to humans of a monoclonal antibody cocktail against rabies
      virus: safety, tolerability, and neutralizing activity.
AB  - Immediate passive immune prophylaxis as part of rabies post-exposure prophylaxis
      (PEP) often cannot be provided due to limited availability of human or equine
      rabies immunoglobulin (HRIG and ERIG, respectively). We report first clinical
      data from two phase I studies evaluating a monoclonal antibody cocktail CL184
      against rabies. The studies included healthy adult subjects in the USA and India
      and involved two parts. First, subjects received a single intramuscular dose of
      CL184 or placebo in a double blind, randomized, dose-escalation trial. Second,
      open-label CL184 (20IU/kg) was co-administered with rabies vaccine. Safety was
      the primary objective and rabies virus neutralizing activity (RVNA) was
      investigated as efficacy parameter. Pain at the CL184 injection site was reported
      by less than 40% of subjects; no fever or local induration, redness or swelling
      was observed. RVNA was detectable from day 1 to day 21 after a single dose of
      CL184 20 or 40IU/kg. All subjects had adequate (>0.5IU/mL) RVNA levels from day
      14 onwards when combined with rabies vaccine. CL184 appears promising as an
      alternative to RIG in PEP.

PMID- 18804137
TI  - Vaccine injection technique and reactogenicity--evidence for practice.
AB  - There are inconsistencies in recommendations and practice with regards to how
      best to administer vaccines. This review evaluates the literature on
      intramuscular vaccine administration technique in primarily paediatric
      populations and concludes from available evidence which aspects of vaccine
      administration are associated with reactogenicity. Variables with best evidence
      to support practice to reduce reactogenicity were: Site of injection--less
      reactogenicity has been noted when the buttock is used rather than the thigh;
      tissue (muscle or subcutaneous)--less reactions are noted when vaccine is
      administered intramuscularly rather than subcutaneously; length of needle--longer
      needles are associated with less reactogenicity. Angle of injection--a 90 degrees
      angle is associated with less reactogenicity than a reduced angle. Despite a need
      for more empirical studies, there appears to be several vaccine administration
      techniques relating to needle angle, length, site and depth of injection that
      result in fewer reactions and these could be considered for public health policy,
      in conjunction with immunogenicity.

PMID- 18804138
TI  - Complete protection against P. berghei malaria upon heterologous prime/boost
      immunization against circumsporozoite protein employing Salmonella type III
      secretion system and Bordetella adenylate cyclase toxoid.
AB  - Sterile immunity against malaria can be achieved by the induction of IFNgamma
      producing CD8(+) T cells that target infected hepatocytes presenting epitopes of
      the circumsporozoite protein (CSP). In the present study we evaluate the
      protective efficacy of a heterologous prime/boost immunization protocol based on
      the delivery of the CD8(+) epitope of Plasmodium berghei CSP into the MHC class I
      presentation pathway, by either a type III secretion system of live recombinant
      Salmonella and/or by direct translocation of a recombinant Bordetella adenylate
      cyclase toxoid fusion (ACT-CSP) into the cytosol of professional antigen
      presenting cells (APCs). A single intraperitoneal application of the recombinant
      ACT-CSP toxoid, as well as a single oral immunization with the Salmonella
      vaccine, induced a specific CD8(+) T cell response, which however conferred only
      a partial protection on mice against a subsequent sporozoite challenge. In
      contrast, a heterologous prime/boost vaccination with the live Salmonella
      followed by ACT-CSP led to a significant enhancement of the CSP-specific T cell
      response and induced complete protection in all vaccinated mice.

PMID- 18804139
TI  - To BCG or not to BCG? Preventing travel-associated tuberculosis in children.
AB  - With the rise in travel to countries with a high prevalence of tuberculosis (TB),
      the risk of travel-associated TB is of increasing concern. However, the use of
      Bacille Calmette-Guerin (BCG) vaccine for the prevention of travel-associated TB
      is a neglected area. We review and discuss national and international
      recommendations and guidelines for the prevention of travel-associated TB in
      children. Three children who developed travel-associated TB disease are described
      to illustrate that current recommendations, and in particular the use of pre
      travel BCG immunisation, are inconsistent and controversial. The wide variation
      in recommendations reflects the paucity of data on the effectiveness of BCG
      immunisation and other preventive strategies in this setting. Until evidence
      based guidelines can be produced, we believe that a low threshold for
      recommending BCG immunisation for travelling children is the safest strategy. A
      practical approach to deciding which children should be immunised with BCG prior
      to travel is presented.

PMID- 18804140
TI  - Improved cell mediated immune responses after successful re-vaccination of non
      responders to the hepatitis B virus surface antigen (HBsAg) vaccine using the
      combined hepatitis A and B vaccine.
AB  - We successfully re-vaccinated hepatitis B virus (HBV) vaccine non-responders
      using a double dose of the combined hepatitis A virus (HAV) and HBV vaccine. The
      hope was to improve priming of hepatitis B surface antigen (HBsAg)-specific cell
      mediated immune response (CMI) by an increased antigen dose and a theoretical
      adjuvant-effect from the local presence of a HAV-specific CMI. A few non
      responders had a detectable HBsAg-specific CMI before re-vaccination. An in vitro
      detectable HBsAg-specific CMI was primed equally effective in non-responders
      (58%) as in first time vaccine recipients (68%). After the third dose a weak,
      albeit significant, association was observed between the magnitude of HBsAg
      specific proliferation and anti-HBs levels. This regimen improves the priming of
      HBsAg-specific CMIs and antibodies.

PMID- 18804141
TI  - Safety assessment of SDA soybean oil: results of a 28-day gavage study and a 90
      day/one generation reproduction feeding study in rats.
AB  - Long chain polyunsaturated fatty acids (LC-PUFAs) in the diet reduce risk of
      cardiac mortality. Fish oils are a dietary source of LC-PUFAs (EPA, DHA) but
      intake is low in Western diets. Adding beneficial amounts of LC-PUFAs to foods is
      limited by their instability and potential to impart off-flavors. Stearidonic
      acid (SDA), a precursor of EPA in man, is more stable than EPA/DHA in food
      matrices. SDA is present in fish oils (0.5-4%) and in nutraceuticals (echium,
      borage oil). Genes for Delta6, Delta15 desaturases were introduced into soybeans
      that convert linoleic and alpha-linolenic acid to SDA (15-30% fatty acids). Since
      addition of SDA soybean oil into human foods increases SDA intake, toxicology
      studies were undertaken to assess its safety. In a 28-day pilot study, rats were
      gavaged with SDA soybean oil at dosages up to 3g/kg body weight/day; no treatment
      related adverse effects were observed. A 90-day/one generation rat reproduction
      study was subsequently conducted where SDA soybean oil was added to diets to
      provide daily doses of 1.5 and 4 g/kg body weight. There were no treatment
      related adverse effects on parental animals or on reproductive performance and
      progeny development.

PMID- 18804142
TI  - Evaluation of dermatological effects of cosmetic formulations containing
      Saccharomyces cerevisiae extract and vitamins.
AB  - Saccharomyces cerevisiae extract (SCE) is used in cosmetics since it can act in
      oxidative stress and improve skin conditions. This study investigated
      dermatological effects of cosmetic formulations containing SCE and/or vitamins A,
      C and E. The formulation studied was supplemented or not (F1: vehicle) with
      vitamins A, C and E esters (F2) or with SCE (F3) or with the combination of
      vitamins and SCE (F4). Formulations were patch tested on back skin of volunteers.
      For efficacy studies, formulations were applied on volunteers and transepidermal
      water loss (TEWL), skin moisture (SM), skin microrelief (SMR) and free radicals
      protection were analysed after 3h, 15 and 30 days of application. Volunteers were
      also asked about efficacy perception. It was observed that F4 provoked a slight
      erythema in one volunteer. All formulations enhanced forearm SM. Only F3 and F4
      presented long term effects on SMR and showed higher texture values; F3 had the
      highest brightness values. Our results suggest that vitamins and SCE showed
      effects in SM and SMR. Only formulations containing SC had long term effects in
      the improvement of SMR. Thus, these kinds of evaluations are very important in
      cosmetics development to evaluate the best risk and benefit correlation.

PMID- 18804143
TI  - Kalopanaxsaponin A induces apoptosis in human leukemia U937 cells through
      extracellular Ca2+ influx and caspase-8 dependent pathways.
AB  - In the present study, we investigated the effect of KPS-A on the apoptotic
      activity and the molecular mechanism of the action in human leukemia. Treatment
      with KPS-A significantly increased apoptotic DNA fragmentation in human
      histiocytic lymphoma U937 cells as shown by DAPI staining, flow cytometry, and
      agarose gel electrophoresis. In addition, stimulation of U937 cell with KPS-A
      induced a series of intracellular events: (1) the activations of caspase-8,
      caspase-9, and caspase-3; (2) the translocations of Bid and Bax proteins to
      mitochondria; (3) the loss of mitochondrial membrane potential; and (4) the
      increased release of cytochrome c to the cytosol. Pretreatment with a specific
      caspases-8, -9 or -3 inhibitor, neutralized the pro-apoptotic activity of KPS-A
      in U937 cells. We further demonstrated that KPS-A markedly induced an increase in
      intracellular Ca2+ level, which was reversed by EGTA, a general calcium chelator,
      but not by TMB-8 and dantrolene, intracellular Ca2+ release blockers. Moreover,
      KPS-A-induced DNA fragmentation and caspase activation were substantially reduced
      in the presence of EGTA. Taken together, these results suggest that KPS-A may
      play therapeutic role for leukemia via the potent apoptotic activity through
      Ca2+/caspases-8/MPT/caspases-9/caspases-3 signaling pathway.

PMID- 18804144
TI  - Antioxidant properties, total phenols and pollen analysis of propolis samples
      from Portugal.
AB  - Pollen analysis, total phenols content and antioxidant activity were studied for
      the first time in Portuguese propolis samples from Bornes and Fundao regions.
      Total phenols content was determined by colorimetric assay and their amount was
      of 329 mg/g of GAE in Bornes sample and 151 mg/g of GAE in Fundao propolis. The
      antioxidant capacity of propolis extracts was assessed through the scavenging
      effects on DPPH (2,2-diphenyl-1-picrylhydrazyl) and reducing power of iron (III)/
      ferricyanide complex assays. A concentration-dependent antioxidative capacity was
      verified in DPPH and reducing power assays. Low values of EC50 on DPPH scavenging
      assay were obtained for Bornes and Fundao propolis (of 6.22 microg/mL and 52.00
      microg/mL, respectively). For reducing power the values were 9.00 microg/mL, for
      Bornes propolis, and 55.00 microg/mL, for Fundao propolis. The high activity of
      propolis from Bornes could be related with their different pollen composition.
      The results obtained indicate that Portuguese propolis is an important source of
      total phenols showing antioxidant properties that could be beneficial for human
      health.

PMID- 18804145
TI  - Increased vulnerability to rotenone-induced neurotoxicity in ceruloplasmin
      deficient mice.
AB  - Ceruloplasmin (Cp) is the strongest ferroxidase in human plasma. Hereditary
      deficiency of this protein, named aceruloplasminemia, is an interesting model to
      elucidate the pathogenesis and pathophysiology of neurodegeneration induced by
      oxidative stress. Enhanced oxidative stress due to excessive iron accumulation is
      observed in the brains of aceruloplasminemia patients. Rotenone, a selective
      mitochondrial complex I inhibitor, induces neurodegeneration mimicking
      Parkinson's disease. We investigated the influence of Cp deficiency upon
      neurodegeneration using rotenone-treated, Cp-deficient mouse brains.
      Immunohistochemical examination showed that acrolein, one of the products of
      lipid peroxides, and ubiquitin were more markedly immunoreacted in the brains of
      rotenone-treated, Cp-deficient mice than in rotenone-untreated, Cp-deficient or
      rotenone-treated, wild-type mice. These molecules were localized in neuronal
      cells. These results suggested that rotenone-induced lipid peroxidation and
      accumulation of ubiquitin immunoreactivity were enhanced in the absence of Cp.
      Therefore, Cp may protect neuronal cells from oxidative stress-induced
      neurodegeneration.

PMID- 18804146
TI  - Alteration of cholinergic, purinergic and sensory neurotransmission in the mouse
      colon of food allergy model.
AB  - It is well known that intestinal anaphylaxis results in a disturbed intestinal
      motility. It is hypothesized that the chronic intestinal anaphylaxis-induced
      changes in the enteric neuronal circuitry cause intestinal motor malfunctions.
      However, detailed mechanisms largely remain unclear. The aim of this study was to
      investigate the pathophysiological role of ATP, which acts as a non-cholinergic
      neurotransmitter and a neuroimmune modulator, in a disturbed intestinal motility
      of food allergy (FA). The FA mice developed allergic diarrhea accompanied with
      chronic inflammation and mast cell hyperplasia in the colon. The excised proximal
      colons (PCs) were suspended in the longitudinal direction in organ baths. In the
      PCs precontracted by KCl (50 mM), contractile responses to exogenous ATP (1 mM)
      were significantly (P < 0.01) higher in FA mice (34.2% of KCl-induced
      precontractions) as compared to control mice (17.2%). Pretreatment with P2
      purinoceptor antagonists [suramin and PPADs] significantly (P < 0.01) reduced the
      ATP-evoked contractions to 7.7% and 1.5% in FA and control PCs, respectively.
      Furthermore, in the presence of inhibitors of cholinergic nerves and capsaicin
      sensitive sensory nerves the electrical field stimulation (EFS; 10Hz)-evoked
      contractions were significantly (P < 0.05) higher in FA mice (65.8% of EFS-evoked
      maximum contractions, n = 6) than those in control mice (47.9%, n = 6). In
      addition, cumulative application of suramin and PPADs further inhibited EFS
      induced contractions by 21.7% in FA mice (n = 6, P < 0.01) and 8.7% in control
      mice (n = 6, P < 0.05). Thus, the present study suggests that the sustained
      alteration in cholinergic, purinergic and sensory neurotransmission contribute to
      the disturbed motility during the chronic intestinal anaphylaxis.

PMID- 18804147
TI  - Dorsal root ganglion neurons induce transdifferentiation of mesenchymal stem
      cells along a Schwann cell lineage.
AB  - It has been reported that mesenchymal stem cells (MSCs) can transdifferentiate
      into Schwann cell-like cells by a series of treatments with a reducing agent,
      retinoic acid and a combination of trophic factors in vitro, and can
      transdifferentiate into myelin-forming cells to repair the demyelinated rat
      spinal cord in vivo. We now report that when co-cultured with dorsal root
      ganglion (DRG) neurons, MSCs were induced to transdifferentiate into Schwann cell
      like cells that had ensheathed DRG axons. Following differentiation, MSCs
      underwent morphological changes similar to those of cultured Schwann cells and
      express GFAP and S100, the marker of Schwann cells. Moreover, 6 weeks later, MSCs
      wrapped their membrane around DRG axons. Further, initiation of myelination was
      observed in the co-cultured DRG neurons, which was determined by signals to MBP
      and this initiation of axon myelination by MSCs is similar to that of Schwann
      cells. However, electron micrographs show that no compact myelin was present in
      the MSCs co-cultures, whereas the Schwann cells co-cultures had formed a
      multilammelar myelin sheath around the axon. These indicate that the release of
      cytokine by DRG neurons may promote the transdifferentiation of MSCs, but is not
      sufficient to elicit compact myelination by transdifferentiated MSCs. These
      results improve our understanding in the mechanism of MSC transdifferentiation,
      and the mechanism underlying ensheathment and myelination by transdifferentiated
      MSCs.

PMID- 18804148
TI  - The vestibular system is integral in regulating plastic alterations in the
      pressor response to free drop mediated by the nonvestibular system.
AB  - Microgravity resulting from free drop elicits a pressor response that involves
      both vestibular and nonvestibular pathways. In rats reared under a 3G environment
      for 2 weeks, plastic alterations in both vestibular- and nonvestibular-mediated
      responses are induced; specifically, the pressor responses involving both
      pathways are reduced [C. Abe, K. Tanaka, C. Awazu, H. Chen, H. Morita, Plastic
      alteration of vestibulo-cardiovascular reflex induced by 2 weeks of 3-G load in
      conscious rats, Exp. Brain Res. 181 (2007) 639-646]. It is currently unknown
      whether plastic alterations in the nonvestibular system depend on the vestibular
      system. To examine this topic, the pressor response to free drop was compared
      between rats with and without vestibular lesion (VL) reared under 1G or 3G
      environments. The pressor response to free drop was 34+/-3mmHg in vestibular
      intact rats reared under 1G, and was significantly attenuated in rats reared
      under a 3G environment for 2 weeks (13+/-3mmHg); however, the pressor response
      was similar between VL-1G (18+/-3mmHg) and VL-3G (19+/-3mmHg) rats. Therefore,
      the 3G environment induced plastic alterations in the pressor response to free
      drop mediated by both the vestibular and nonvestibular systems, and the
      vestibular system is indispensable for induction of the plastic alteration of the
      nonvestibular-meidated pressor response to free drop.

PMID- 18804149
TI  - Echo frequency selectivity of duration-tuned inferior collicular neurons of the
      big brown bat, Eptesicus fuscus, determined with pulse-echo pairs.
AB  - During hunting, insectivorous bats such as Eptesicus fuscus progressively vary
      the repetition rate, duration, frequency and amplitude of emitted pulses such
      that analysis of an echo parameter by bats would be inevitably affected by other
      co-varying echo parameters. The present study is to determine the variation of
      echo frequency selectivity of duration-tuned inferior collicular neurons during
      different phases of hunting using pulse-echo (P-E) pairs as stimuli. All
      collicular neurons discharge maximally to a tone at a particular frequency which
      is defined as the best frequency (BF). Most collicular neurons also discharge
      maximally to a BF pulse at a particular duration which is defined as the best
      duration (BD). A family of echo iso-level frequency tuning curves (iso-level FTC)
      of these duration-tuned collicular neurons is measured with the number of
      impulses in response to the echo pulse at selected frequencies when the P-E pairs
      are presented at varied P-E duration and gap. Our data show that these duration
      tuned collicular neurons have narrower echo iso-level FTC when measured with BD
      than with non-BD echo pulses. Also, IC neurons with low BF and short BD have
      narrower echo iso-level FTC than IC neurons with high BF and long BD have. The
      bandwidth of echo iso-level FTC significantly decreases with shortening of P-E
      duration and P-E gap. These data suggest that duration-tuned collicular neurons
      not only can facilitate bat's echo recognition but also can enhance echo
      frequency selectivity for prey feature analysis throughout a target approaching
      sequence during hunting. These data also support previous behavior studies
      showing that bats prepare their auditory system to analyze expected returning
      echoes within a time window to extract target features after pulse emission.

PMID- 18804150
TI  - The stop null mice model for schizophrenia displays [corrected] cognitive and
      social deficits partly alleviated by neuroleptics.
AB  - Recently evidence has accumulated that schizophrenia can arise from primary
      synaptic defects involving structural proteins particularly, microtubule
      associated proteins. Previous experiments have demonstrated that a STOP (stable
      tubule only peptide) gene deletion in mice leads to a phenotype mimicking some
      aspects of positive symptoms classically observed in schizophrenic patients. In
      the current study, we determined if STOP null mice demonstrate behavioral
      abnormalities related to the social and cognitive impairments of schizophrenia.
      Compared with wild-type mice, STOP null mice exhibited deficits in the non
      aggressive component of social recognition, short term working memory and social
      and spatial learning. As described in humans, learning deficits in STOP null mice
      were poorly sensitive to long term treatment with typical neuroleptics. Since
      social and cognitive dysfunction have consistently been considered as central
      features of schizophrenia, we propose that STOP null mice may provide a useful
      model to understand the neurobiological correlates of social and cognitive
      defects in schizophrenia and to develop treatments that better target these
      symptoms.

PMID- 18804151
TI  - Morphine attenuates the expression of sensitization to ethanol, but opioid
      antagonists do not.
AB  - Behavioral sensitization to ethanol is characterized by an increased locomotor
      activity after repeated exposure. A great variability exists among species and
      strains in the development of sensitization. There is a growing amount of
      evidence to indicate that the opioid system is involved in alcoholism; it is
      possible, therefore, that this system also modulates the sensitization to
      ethanol. In this study we evaluated the role of the opioid system in determining
      the variability of the sensitized response to ethanol. Mice received repeated
      administrations of ethanol (2.2 g/kg) or saline every other day for 10 days.
      According to their locomotor response on the last day of treatment, ethanol
      treated animals were classified into two groups: sensitized or non-sensitized
      mice. After the treatment, mice were submitted to four challenges 48 h apart. In
      experiments 1 and 2, mice were challenged, respectively, with i.p. administration
      of opioid antagonists (naloxone or naltrexone) or an opioid agonist (morphine),
      followed immediately by 2.2 g/kg ethanol. In experiment 3, animals received
      morphine by i.c.v., followed by 2.2 g/kg of ethanol (i.p.). Pretreatment with
      opioid antagonists (naloxone or naltrexone) did not block the expression of
      ethanol sensitization; however pretreatment with morphine attenuated the
      increased locomotor activity after ethanol administration in sensitized mice. In
      experiment 4, after the ethanol or saline treatment, mice brains were processed
      and brain mu opioid binding was assessed by autoradiography using [3H]D-Ala2,N
      mePhe4, Gly-ol5-enkephalin ([3H]DAMGO). No differences were seen between any of
      the groups of mice, so the agonist effect is not likely to be mediated by
      differences in binding to mu opioid receptors.

PMID- 18804152
TI  - The septal area, site for the central regulation of penile erection during waking
      and rapid eye movement sleep in rats: a stimulation study.
AB  - The effects of electrical stimulation to the septum on penile erections in rats
      were examined to clarify the mechanisms for regulation of erectile responses
      during different states of vigilance. Penile responses were assessed by changes
      in pressure in the corpus spongiosum of penis (CSP) and electromyography (EMG) of
      the bulbospongiosus (BS) muscle. In anesthetized and un-anesthetized rats,
      stimulation in and around the septum induced three erectile patterns; 1) a Normal
      type response, which was indistinguishable from a spontaneous erection,
      characterized by a slow increase in CSP pressure with sharp CSP pressure peaks
      associated with BS muscle bursts, 2) Mixed type response, in which high frequency
      CSP pressure peaks were followed by a Normal type response, and 3) a Prolonged
      type response, evoked only in the anesthetized rat, consisting of a single sharp
      CSP peak followed by a slow increase in CSP pressure and a return to baseline
      with multiple subsequent events repeated for up to 960 s. In addition, a
      Micturition type response was also observed involving high frequency CSP pressure
      oscillations similar to the pressure pattern seen during spontaneous micturition.
      We found that erections were induced after stimulation to the lateral septum
      (LS), but not from the medial septum (MS). In anesthetized rats, a few responses
      were also obtained following stimulation of the horizontal limb of diagonal band
      (HDB). In un-anesthetized rats, responses were also induced from the HDB and the
      ventral limb of diagonal band (VDB) and the adjoining areas. The effective sites
      for eliciting erection during rapid eye movement (REM) sleep were located in the
      dorsal and intermediate parts of the LS, whereas the ventral part of the LS was
      the most effective site for eliciting erections during wakefulness. These results
      suggest a functional role for penile erection in the septum, and further suggest
      that subdivisions of the LS may have different roles in the regulation of penile
      erection during wakefulness and REM sleep.

PMID- 18804153
TI  - Evolutionary mechanisms underlying the functional divergence of duplicate genes
      involved in vertebrates' circadian rhythm pathway.
AB  - Circadian rhythms, that are governed physiologically and behaviorally by
      endogenous clock, have been described in many species. Living organisms use this
      endogenous circadian clock to anticipate environmental transitions, perform
      activities at biologically advantageous times during the day, and undergo
      characteristic seasonal responses. Gene duplication is one of the most important
      mechanisms in the evolution of gene diversity. After duplication, one or both of
      duplicates can accumulate amino acid changes, thereby promoting functional
      divergence through the action of natural selection. The circadian system, like
      many other multigene families, has undergone this genetic revolution, and so
      circadian genes that are found in single copies in insects are duplicated in
      vertebrates. We analyzed six groups of genes involved in vertebrates' circadian
      rhythm pathway to find signatures of molecular evolutionary processes such as
      gene duplication, natural selection, recombination, and functional divergence.
      The obtained results, then, were used to determine what evolutionary forces have
      influenced the fates of duplicated genes of each group. We showed in this
      research that recombination has not been widespread during the evolution of
      circadian genes and that purifying selection has been the prominent natural
      pressure operating on circadian genes. We also showed that the evolution of
      circadian genes has been depended on gene duplication and functional divergence.
      Finally, we put forward models best describing the evolutionary fates of
      circadian duplicates.

PMID- 18804154
TI  - Rubratoxin B induces interleukin-6 secretion in mouse white adipose tissues and
      3T3-L1 adipocytes.
AB  - Rubratoxin B is a mycotoxin that causes hepatic fatty changes. We examined
      whether white adipose tissue (WAT) contributes to rubratoxin B toxicity through
      effects on interleukin (IL)-6. Rubratoxin B was intraperitoneally injected into
      mice at 1.5mg/kg. Urinary albumin and macrophage inflammatory protein (MIP)-2
      secretion were increased 24h after treatment with rubratoxin B. Rubratoxin B was
      previously reported to induce IL-6 secretion, although the secreting tissue was
      unknown. Here, rubratoxin B prominently augmented IL-6 transcription in
      epididymal WAT and to a lesser extent in perirenal WAT and liver. Rubratoxin B
      may thus exert its toxicity partly through IL-6 secretion from WATs. In contrast,
      MIP-2 gene expression increased only in liver. To examine the specific
      involvement of adipocytes, we used mouse 3T3-L1 cells, an in vitro
      differentiation model of adipocytes. Expression of IL-6 and MIP-2 mRNA in 3T3-L1
      adipocytes after 24h of rubratoxin B treatment increased dose-dependently.
      Rubratoxin B also increased IL-6 and MIP-2 secretion from 3T3-L1 adipocytes. The
      increase in IL-6 secretion was markedly higher than the increase in IL-6 gene
      transcription, indicating that rubratoxin B-induced secretion of IL-6 from 3T3-L1
      adipocytes is chiefly controlled post-transcriptionally. Rubratoxin B is thus the
      first mycotoxin known to exert its toxicity through effects on WATs.

PMID- 18804155
TI  - On the thermodynamics of cocrystal formation.
AB  - The thermodynamics underpinning cocrystal formation are derived. The results
      provide the pharmaceutical scientist with the foundation to experimentally assess
      the thermodynamic stability of a cocrystal with respect to its component forms.
      Data for the carbamazepine-nicotinamide system are discussed as an example.

PMID- 18804156
TI  - Effect of powder characteristics on oral tablet disintegration.
AB  - This report describes an investigation of the factors affecting disintegration
      time in the mouth (DTM) of rapidly disintegrating tablets. The relation between
      DTM and stationary time of upper punch displacement (STP) was examined using a
      tableting process analyzer (TabAll). Results indicated that the bulk density of
      mixed excipient powder used for tablet preparation affects both DTM and STP. As
      the value of bulk density increased, STP became longer and DTM shorter. The
      results of a combination of granules and powder with or without a drug showed
      liner relation between apparent volume (reciprocal of bulk density) and DTM
      (r(2)=0.7332). For a DTM less than 60 s, a formulation with a bulk density
      greater 0.5 g/mL should be chosen with a compression force of 5 kN. The hardness
      of tablets could be greater than 3 kg if at least one high-compressibility
      excipient was used in the formulation.

PMID- 18804157
TI  - Efficient encapsulation of a water-soluble corticosteroid in biodegradable
      nanoparticles.
AB  - Solid nanoparticles consisting of biodegradable polymers have emerged as a
      promising carrier for various drugs, but unfortunately the encapsulation of drugs
      remains challenging. In this study, a technique for encapsulation of water
      soluble drugs in solid nanoparticles was developed. Nanoparticles were prepared
      from a blend of biodegradable polymers, including poly(lactic acid) (PLA) and
      poly(lactic/glycolic acid) (PLGA), and monomethoxypolyethyleneglycol-polylactide
      block copolymer by an oil-in-water solvent diffusion method. Betamethasone sodium
      phosphate (BP) was not encapsulated by the nanoparticles due to its
      hydrophilicity, but it was effectively encapsulated in the presence of
      appropriate amounts of zinc and diethanolamine. It was found that BP formed an
      ionic complex with zinc at a certain pH range obtained by addition of
      diethanolamine. Furthermore, a carboxyl group located at the end of PLA/PLGA was
      shown to be essential for encapsulation of BP in nanoparticles, and the molar
      ratio among BP, zinc, and carboxyl groups in various nanoparticles was almost
      constant. These results strongly suggested that the encapsulation was promoted by
      zinc creating an ionic bridge between a carboxyl group on PLA/PLGA and a
      phosphate group on BP. This technique for entrapment of water-soluble drugs in
      solid biodegradable nanoparticles may expand the use of nanoparticles for various
      therapeutic applications.

PMID- 18804158
TI  - A holistic approach to managing palm oil mill effluent (POME): biotechnological
      advances in the sustainable reuse of POME.
AB  - During the last century, a great deal of research and development as well as
      applications has been devoted to waste. These include waste minimization and
      treatment, the environmental assessment of waste, minimization of environmental
      impact, life cycle assessment and others. The major reason for such huge efforts
      is that waste generation constitutes one of the major environmental problems
      where production industries are concerned. Until now, an increasing pressure has
      been put on finding methods of reusing waste, for instance through cleaner
      production, thus mirroring rapid changes in environmental policies. The palm oil
      industry is one of the leading industries in Malaysia with a yearly production of
      more than 13 million tons of crude palm oil and plantations covering 11% of the
      Malaysian land area. However, the production of such amounts of crude palm oil
      result in even larger amounts of palm oil mill effluent (POME), estimated at
      nearly three times the quantity of crude palm oil. Normally, POME is treated
      using end-of-pipe processes, but it is worth considering the potential value of
      POME prior to its treatment through introduction of a cleaner production. It is
      envisaged that POME can be sustainably reused as a fermentation substrate in the
      production of various metabolites, fertilizers and animal feeds through
      biotechnological advances. The present paper thus discusses various technically
      feasible and economically beneficial means of transforming the POME into low or
      preferably high value added products.

PMID- 18804159
TI  - In vitro pharmacogenomic database and chemosensitivity predictive genes in
      gastric cancer.
AB  - Gastric cancer is one of the most common cancers worldwide, and there are
      clinical caveats in predicting tumor response to chemotherapy. This study
      describes the construction of an in vitro pharmacogenomic database, and the
      selection of genes associated with chemosensitivity in gastric cancer cell lines.
      Gene expression and chemosensitivity databases were integrated using the Pearson
      correlation coefficient to give the GC-matrix. The 85 genes were selected that
      were commonly associated with chemosensitivity of the major anticancer drugs. We
      then focused on the genes that were highly correlated with each specific drug.
      Classification of cell lines based on the set of genes associated with each drug
      was consistent with the division into resistant or sensitive groups according to
      the chemosensitivity results. The GC-matrix of the gastric cancer cell line
      database was used to identify different sets of chemosensitivity-related genes
      for specific drugs or multiple drugs.

PMID- 18804160
TI  - Retinal folding in the term rabbit fetus-Developmental abnormality or fixation
      artifact?
AB  - Preclinical reproductive toxicology studies must be performed to provide
      information on the risk of causing fetal harm in pregnant patients. These studies
      detect fetal malformations, which may or may not be drug-related adverse events.
      In the rabbit fetus, "slight retinal folding" is commonly observed; there is
      anecdotal evidence that these folds may be caused by routine (Bouin's fluid)
      fixation. This study used magnetic resonance imaging (MRI) to assess rabbit
      retinal architecture in fresh specimens, which was then reassessed following
      Bouin's fluid fixation. A total of 30 fetuses from 5 litters were imaged. No
      retinal folding was detected in fresh specimens but it was observed in a majority
      of fetuses post-fixation. The use of Davidson's fixative followed by Bouin's
      fluid showed a markedly lower incidence of "slight retinal folding". CONCLUSION:
      slight retinal folds in the rabbit fetus are likely artifactual and can be
      reduced using Davidson's fixation prior to Bouin's.

PMID- 18804161
TI  - Oxidative stress and chronological aging in glycogen-phosphorylase-deleted yeast.
AB  - Chronological aging in yeast resembles aging in mammalian, postmitotic tissues.
      Such chronological aging begins with entrance into the stationary phase after the
      nutrients are exhausted. Many changes in metabolism take place at this moment,
      and survival in this phase strongly depends on oxidative-stress resistance. In
      this study, hypo- and hyperglycogenic phenotypes of Saccharomyces cerevisiae
      strains with deletions of carbohydrate-metabolism enzymes were selected, and a
      comparison of their chronological longevities was made. Stress sensitivity, ROS,
      and apoptosis markers during aging were analyzed in the emerged candidates. Among
      the strains that accumulated greater amounts of glycogen, the deletion of
      glycogen phosphorylase, gph1delta, was unique in showing a shortened life span,
      stress intolerance, and higher levels of ROS during its survival. The
      transcription of superoxide dismutase genes during survival was three- to
      fourfold lower in gph1delta. Extra copies of SOD1/2 counteracted the stress
      sensitivity and the accelerated aging of gph1delta. In conclusion, the lack of
      gph1 produced a rapidly aging strain, which could be attributed, at least in
      part, to the weakened stress resistance associated with the decreased expression
      of both SODs. Gph1p seems to be a candidate in a scenario that could link early
      metabolic changes with other targets of the stress response during stationary
      phase survival.

PMID- 18804162
TI  - Identification and molecular characterization of a novel PDE4D11 cAMP-specific
      phosphodiesterase isoform.
AB  - Here we report the cloning and characterization of a novel PDE4D isoform
      (PDE4D11) identified in mouse brain cDNA. This novel isoform has a unique isoform
      specific 5'-UTR and N-terminal sequence, whereas, downstream regulatory N
      terminal and catalytic C-terminal regions are homologous to other long PDE4D
      isoforms (Ex2-15). In silico analysis of PDE4D11 cDNA transcript identified the
      predicted translational start site and the use of a different transcriptional
      start site compared to other PDE4D isoforms. This isoform is ubiquitously
      expressed in different mouse tissues, particularly in the brain, liver and
      spleen. In the brain, PDE4D11 expression levels increased in the cerebellum, but
      decreased in the hippocampus with progressive age, highlighting a potential role
      for this isoform in the development of the brain. When transfected in vitro into
      murine neuroblastoma cells PDE4D11_EGFP expression is cytosolic, consistent with
      other long PDE4D isoforms. The appearance of cytosolic protein aggregates in
      discrete microdomains with this isoform, however, may represent a method of
      compartmentalizing PDE4D11 activity. The novel 5'-sequence of PDE4D11 is
      conserved among higher vertebrates including human, monkey, dog, horse and rat.
      Identification of this new isoform highlights the mutliplicity of unique PDE4D
      isoforms and their potential importance in regulating cAMP levels through
      compartmentalization and cell-specific expression and underscores the importance
      of understanding the functional role of each isoform in the development of
      specific drugs for the treatment of memory disorders.

PMID- 18804163
TI  - Inhibition of GSK-3beta promotes survival and proliferation of megakaryocytic
      cells through a beta-catenin-independent pathway.
AB  - The interaction of thrombopoietin (TPO) with its receptor c-Mpl initiates
      intracellular signals that are critical for megakaryopoiesis. Previously we and
      others have shown that TPO activates PI3K and Akt and that this pathway is
      important for megakaryocyte growth. Here, we investigate the importance of the
      Akt substrate glycogen synthase kinase (GSK)-3beta in TPO signaling. GSK-3beta is
      phosphorylated and inhibited by Akt as part of the PI3K pathway. GSK-3beta can
      also be inhibited by Wnt signaling through a distinct mechanism, leading to
      reduced phosphorylation and accumulation of the transcription factor beta
      catenin. Therefore, we asked if TPO and Wnt3a can both inhibit GSK-3beta in
      megakaryocytic cells, and if they can act synergistically to promote cell growth.
      Although both TPO and specific chemical inhibitors of GSK-3beta result in
      increased survival and proliferation in a megakaryocytic cell line model,
      treatment with Wnt3a failed to increase cell growth either in the absence or
      presence of TPO, despite inducing high levels of beta-catenin. Similarly,
      expression of a constitutively active version of beta-catenin did not increase
      cell growth either in the absence or presence of TPO, suggesting that the effects
      of GSK-3beta inhibition downstream of TPO signaling are distinct from those
      induced by Wnt3a and independent of beta-catenin. The growth promoting effects of
      TPO are not mediated by either of the two known GSK-3beta targets, cyclin D or
      HIF-1alpha. We conclude that GSK-3beta is phosphorylated and inhibited by TPO
      induced Akt, promoting survival and proliferation in megakaryocytic cells through
      a pathway that does not involve beta-catenin.

PMID- 18804164
TI  - Tetraspanins affect myeloma cell fate via Akt signaling and FoxO activation.
AB  - Myeloma cell interface with microenvironmental components is critical to cell
      growth and survival and perceived as a major obstacle for effective disease
      treatment. Hence, molecules that facilitate cell-cell and cell-ECM interactions
      are particularly important. We have previously shown that re-expression of
      membranal microdomain organizers, tetraspanins CD81 and CD82, caused myeloma cell
      death. Herein we demonstrate that the anti-myeloma effect of CD81/CD82 involves a
      down-regulation of Akt, activation of FoxO transcription factors and a decrease
      in active mTOR and mTOR/rictor. We go on to show in a breast cancer cell line
      model that Akt dependent cells are more sensitive to the tetraspanin
      overexpression. Moreover, expression of a constitutively active Akt increased
      survival of CD81/CD82 transfected myeloma cell lines. Akt and mTOR afford
      attractive therapeutic targets in cancer yet, due to pathways' interactions,
      inhibitors of mTOR frequently activate Akt and vise versa. Our results
      demonstrate co-repression of both by CD81/CD82 implying that tetraspanins may
      serve as "switches" modulating pathways rather than blocking a single factor and
      constitute a promising therapeutic strategy in Akt dependent pathological
      conditions. The possibility that the tetraspanins affect metabolic control is
      broached as well.

PMID- 18804165
TI  - Intraspecific tolerance of Metarhizium anisopliae conidia to the upper thermal
      limits of summer with a description of a quantitative assay system.
AB  - Conidial tolerance to the upper thermal limits of summer is important for fungal
      biocontrol agents, whose conidia are formulated into mycoinsecticides for field
      application. To develop an efficient assay system, aerial conidia of eight
      Metarhizium anisopliae, four M. anisopliae var. anisopliae, and six M. anisopliae
      var. acridum isolates with different host and geographic origins were wet
      stressed for <or=180 min at 48 degrees C or incubated for 14 d colony growths at
      10-35 degrees C. The survival ratios (relative to unstressed conidia) of each
      isolate, examined at 15-min intervals, fit a logistic equation (r2>or=0.975),
      yielding median lethal times (LT50s) of 14.3-150.3 min for the 18 isolates
      stressed at 48 degrees C. Seven grasshopper isolates from Africa had a mean LT50
      of 110 (73-150) min, but could not grow at 10 or 15 degrees C. The mean LT50 of
      five non-grasshopper isolates capable of growing at 10-35 degrees C was 16 (10
      26) min only. Three isolates with typically low (type I), medium (type II), and
      high (type III) levels of tolerance to 48 degrees C were further assayed for
      <or=4-d tolerance of their conidia to the wet stress at 38, 40, 42, or 45 degrees
      C. The resultant LT50s decreased to 20, 53 and 167 min at 48 degrees C from 507,
      1612, and 8256 min at 38 degrees C for types I, II and III, respectively. For the
      distinguished types, the logarithms of the LT50s were significantly correlated to
      the temperatures of 38-48 degrees C with an inverse linearity (r2>or=0.88). The
      method developed to assay quantitatively fungal thermotolerance would be useful
      for screening of fungal candidates for improved pest control in summer.

PMID- 18804166
TI  - Tweaking biological switches through a better understanding of bistability
      behavior.
AB  - Many biological events are binary. The switch between mutually exclusive OFF to
      ON state in response to a stimulus is frequently mediated by a control circuit
      with a positive and/or a negative feedback. Such a system typically exhibits
      hysteresis with its switching ON and OFF stimulus levels dependent on the current
      state of the system. The system can be shown to be bistable both experimentally
      and mathematically. Work to synthesize such switches by combining natural or
      engineered components has begun to illustrate the potential of such control
      circuits in many areas of applications.

PMID- 18804167
TI  - Synaptic clustering by dendritic signalling mechanisms.
AB  - Dendritic signal integration is one of the fundamental building blocks of
      information processing in the brain. Dendrites are endowed with mechanisms of
      nonlinear summation of synaptic inputs leading to regenerative dendritic events
      including local sodium, NMDA and calcium spikes. The generation of these events
      requires distinct spatio-temporal activation patterns of synaptic inputs. We
      hypothesise that the recent findings on dendritic spikes and local synaptic
      plasticity rules suggest clustering of common inputs along a subregion of a
      dendritic branch. These clusters may enable dendrites to separately threshold
      groups of functionally similar inputs, thus allowing single neurons to act as a
      superposition of many separate integrate and fire units. Ultimately, these
      properties expand our understanding about the computational power of neuronal
      networks.

PMID- 18804168
TI  - 3D micro-scale deformations of wood in bending: synchrotron radiation muCT data
      analyzed with digital volume correlation.
AB  - A micro-scale three-point-bending experiment with a wood specimen was carried out
      and monitored by synchrotron radiation micro-computed tomography. The full three
      dimensional wood structure of the 1.57x3.42x0.75mm(3) specimen was reconstructed
      at cellular level in different loading states. Furthermore, the full three
      dimensional deformation field of the loaded wood specimen was determined by
      digital volume correlation, applied to the reconstructed data at successive
      loading states. Results from two selected regions within the wood specimen are
      presented as continuous displacement and strain fields in both 2D and 3D. The
      applied combination of synchrotron radiation micro-computed tomography and
      digital volume correlation for the deformation analysis of wood under bending
      stress is a novel application in wood material science. The method offers the
      potential for the simultaneous observation of structural changes and quantified
      deformations during in situ micro-mechanical experiments. Moreover, the high
      spatial resolution allows studying the influence of anatomical features on the
      fracture behaviour of wood. Possible applications of this method range from bio
      mechanical observations in fresh plant tissue to fracture mechanics aspects in
      structural timber.

PMID- 18804169
TI  - Biogeography and evolution of body size and life history of African frogs:
      phylogeny of squeakers (Arthroleptis) and long-fingered frogs (Cardioglossa)
      estimated from mitochondrial data.
AB  - The evolutionary history of living African amphibians remains poorly understood.
      This study estimates the phylogeny within the frog genera Arthroleptis and
      Cardioglossa using approximately 2400 bases of mtDNA sequence data (12S, tRNA
      Valine, and 16S genes) from half of the described species. Analyses are conducted
      using parsimony, maximum likelihood, and Bayesian methods. The effect of
      alignment on phylogeny estimation is explored by separately analyzing alignments
      generated with different gap costs and a consensus alignment. The consensus
      alignment results in species paraphyly, low nodal support, and incongruence with
      the results based on other alignments, which produced largely similar results.
      Most nodes in the phylogeny are highly supported, yet several topologies are
      inconsistent with previous hypotheses. The monophyly of Cardioglossa and of
      miniature species previously assigned to Schoutedenella was further examined
      using Templeton and Shimodaira-Hasegawa tests. Cardioglossa monophyly is rejected
      and C. aureoli is transferred to Arthroleptis. These tests do not reject
      Schoutedenella monophyly, but this hypothesis receives no support from non
      parametric bootstrapping or Bayesian posterior probabilities. This phylogeny
      provides a framework for reconstructing historical biogeography and analyzing the
      evolution of body size and life history. Direct development and miniaturization
      appear at the base of Arthroleptis phylogeny concomitant with a range expansion
      from Central Africa to throughout most of sub-Saharan Africa.

PMID- 18804170
TI  - A survey of nonribosomal peptide synthetase (NRPS) genes in Aspergillus nidulans.
AB  - The genome of Aspergillus nidulans carries 27 genes encoding nonribosomal peptide
      synthetase (NRPS) structures, although only five of these forming peptides and
      amino acid containing metabolites have been identified so far. This manuscript
      describes domain structures, substrate binding pockets and related genes and gene
      clusters and summarizes our current state of product prediction of fungal NRPS
      systems.

PMID- 18804171
TI  - Exogenous and endogenous corticosterone alter feather quality.
AB  - We investigated how exogenous and endogenous glucocorticoids affect feather
      replacement in European starlings (Sturnus vulgaris) after approximately 56% of
      flight feathers were removed. We hypothesized that corticosterone would retard
      feather regrowth and decrease feather quality. After feather regrowth began,
      birds were treated with exogenous corticosterone or sham implants, or endogenous
      corticosterone by applying psychological or physical (food restriction)
      stressors. Exogenous corticosterone had no impact on feather length and vane
      area, but rectrices were lighter than controls. Exogenous corticosterone also
      decreased inter-barb distance for all feathers and increased barbule number for
      secondaries and rectrices. Although exogenous corticosterone had no affect on
      rachis tensile strength and stiffness, barbicel hooking strength was reduced.
      Finally, exogenous corticosterone did not alter the ability of Bacillus
      licheniformis to degrade feathers or affect the number of feathers that failed to
      regrow. In contrast, endogenous corticosterone via food restriction resulted in
      greater inter-barb distances in primaries and secondaries, and acute and chronic
      stress resulted in greater inter-barb distances in rectrices. Food-restricted
      birds had significantly fewer barbules in primaries than chronic stress birds and
      weaker feathers compared to controls. We conclude that, although exogenous and
      endogenous corticosterone had slightly different effects, some flight feathers
      grown in the presence of high circulating corticosterone are lighter, potentially
      weaker, and with altered feather micro-structure.

PMID- 18804172
TI  - Seasonal acclimatization of metabolism in Eurasian tree sparrows (Passer
      montanus).
AB  - Acclimatization to winter conditions is an essential prerequisite for survival of
      small passerines of the northern temperate zone. Changes in photoperiod, ambient
      temperature and food availability trigger seasonal acclimatization in physiology
      and behavior of many birds. In the present study, seasonal adjustments in several
      physiological, hormonal, and biochemical markers were examined in wild-captured
      Eurasian tree sparrows (Passer montanus) from the Heilongjiang Province in China.
      In winter sparrows had higher body mass and basal metabolic rate (BMR).
      Consistently, the dry mass of liver, heart, gizzard, small intestine, large
      intestine and total digestive tract were higher in winter than in that in summer.
      The contents of mitochondrial protein in liver, and state-4 respiration and
      cytochrome c oxidase (COX) activity in liver and muscle increased significantly
      in winter. Circulating level of serum triiodothyronine (T3) was significantly
      higher in winter than in summer. Together, these data suggest that tree sparrows
      mainly coped with cold by enhancing thermogenic capacities through increased
      organ masses and heightened activity of respiratory enzymes activities. The
      results support the view that prominent winter increases in BMR are
      manifestations of winter acclimatization in tree sparrows and that seasonal
      variation in metabolism in sparrows is similar to that in other small temperate
      wintering birds.

PMID- 18804173
TI  - Expanding the functional diversity of proteins through cysteine oxidation.
AB  - The polarizable sulfur atom in cysteine is subject to numerous post-translational
      oxidative modifications in the cellular milieu, which regulates a wide variety of
      biological phenomena such as catalysis, metal binding, protein turnover, and
      signal transduction. The application of chemical rationale to describe the
      features of different cysteine oxoforms affords a unique perspective on this
      rapidly expanding field. Moreover, a chemical framework broadens our
      understanding of the functional roles that specific cysteine oxidation states can
      play and facilitates the development of mechanistic proposals, which can be
      tested in both biochemical and cellular studies.

PMID- 18804174
TI  - Electron transfer in peptides and proteins.
AB  - Proteins and peptides use their amino acids as medium for electron-transfer
      reactions that occur either in single-step superexchange or in multistep hopping
      processes. Whereas the rate of the single-step electron transfer dramatically
      decreases with the distance, a hopping process is less distance dependent.
      Electron hopping is possible if amino acids carry oxidizable side chains, like
      the phenol group in tyrosine. These side chains become intermediate charge
      carriers. Because of the weak distance dependency of hopping processes, fast
      electron transfer over very long distances occurs in multistep reactions, as in
      the enzyme ribonucleotide reductase.

PMID- 18804175
TI  - Has nature already identified all useful antibacterial targets?
AB  - Novel antimicrobial targets are urgently needed to overcome rising antibiotic
      resistance of important human pathogens. However, evidence from previous
      antimicrobial screenings, in silico analysis, and experimental target evaluation
      suggests that the number of novel bacterial broad-spectrum targets might be
      severely limited. This is because of the poor conservation of genes among diverse
      bacterial pathogens, partial functional redundancy and nutrient-rich host
      environments. Remaining opportunities under these circumstances include the
      development of narrow-spectrum antibiotics against specific pathogens and the
      exploration of target combinations.

PMID- 18804176
TI  - Macrolide myths.
AB  - In spite of decades of research, our knowledge of the mode of interaction of
      macrolide antibiotics with their ribosomal target and of the mechanism of action
      of these drugs remain fragmentary. Experimental facts obtained over the past
      several years question some of the concepts that were viewed as a 'common
      knowledge'. This review focuses on certain aspects of binding and action of
      macrolides that may need re-evaluation in view of the new findings.

PMID- 18804177
TI  - Addressing the frustrations of finding new effective antibacterials to combat
      drug resistant bacteria.

PMID- 18804178
TI  - Tests for genotoxicity and mutagenicity of furan and its metabolite cis-2-butene
      1,4-dial in L5178Y tk+/- mouse lymphoma cells.
AB  - Furan is found in various food items and is cytotoxic and carcinogenic in the
      liver of rats and mice. Metabolism of furan includes the formation of an
      unsaturated dialdehyde, cis-2-butene-1,4-dial (BDA). In view of the
      multifunctional electrophilic reactivity of BDA, adduct formation with protein
      and DNA may explain some of the toxic effects. Short-term tests for genotoxicity
      of furan in mammalian cells are inconclusive, little is known for BDA. We
      investigated BDA generated by hydrolysis of 2,5-diacetoxy-2,5-dihydrofuran for
      genotoxicity in L5178Y tk+/- mouse lymphoma cells using standard procedures for
      the comet assay, the micronucleus test, and the mouse lymphoma thymidine kinase
      gene mutation assay, using 4-h incubation periods. Cytotoxicity was remarkable:
      cell viability at concentrations>or=50 microM was reduced to <50%. In the dose
      range up to 25 microM, viability was >90%. Measures of comet-tail length and
      thymidine-kinase mutant frequency were increased 1.6- and 2.4-fold above control,
      respectively. Analysis of three fully independent replicates with a linear mixed
      effects model showed a highly significant increase with concentration for both
      endpoints. Compared to methyl methanesulfonate used as a positive control, BDA
      was of similar potency with respect to genotoxicity, but it was much more
      cytotoxic. Furan added to cell cultures at doses that resulted in time-averaged
      effective concentrations of up to 3100 microM was neither cytotoxic nor
      genotoxic. A potential cross-linking activity of BDA was investigated by checking
      whether gamma radiation-induced DNA migration in the comet assay could be reduced
      by pre-treatment with BDA. In contrast to the effect of the positive control
      glutaraldehyde, BDA treatment did not reduce the comet tail length. On the
      contrary, an increase was observed at >or=100 microM BDA, which was attributable
      to early apoptotic cells. Although BDA was found to be a relatively potent
      genotoxic agent in terms of the concentration necessary to double the background
      measures, cytotoxicity strongly limited the concentration range that produced
      interpretable results. This may explain some of the inconclusive results and
      indicates that non-genotoxic effects must be taken into account in the discussion
      of the modes of toxic and carcinogenic action of furan.

PMID- 18804179
TI  - Involvement of hydrogen peroxide in chromosomal aberrations induced by green tea
      catechins in vitro and implications for risk assessment.
AB  - Catechins, which are polyphenol compounds found in abundance in green tea, have
      elicited high interest due to their beneficial effects on health. Catechins have
      also been demonstrated to induce chromosomal aberrations in vitro, although no
      clastogenicity was confirmed in studies in vivo. We investigated the mechanism of
      catechin-induced chromosomal aberrations in CHL/IU cells. Addition of catalase
      suppressed chromosomal aberrations, indicating involvement of hydrogen peroxide
      (H2O2). We confirmed that substantial amounts of H2O2 are generated when
      catechins are incubated under in vitro culture conditions, whereas,
      interestingly, extremely low amounts of H2O2 were detected when catechins were
      incubated at the same concentration in water. Generation of H2O2 increased
      steeply above pH 6, indicating that pH is a key factor in determining how much
      H2O2 is generated via catechins in vitro. Our assessment indicates that humans
      have practically non-existent exposure to H2O2 when catechins are ingested in a
      beverage. Polyphenols, including catechins, are known to act as antioxidants due
      to their reducing potential. However, under in vitro culture conditions,
      catechins are thought to act primarily as pro-oxidants by reducing ambient or
      dissolved oxygen to form H2O2. Based on the above observations, we conclude that
      in vitro culture conditions as currently employed are inappropriate to address
      genotoxicity concerns regarding polyphenols, including catechins.

PMID- 18804180
TI  - Particulate matter inhibits DNA repair and enhances mutagenesis.
AB  - Exposure to ambient air pollution has been associated with adverse health effects
      including lung cancer. A recent epidemiology study has established that each 10
      microg/m3 elevation in long-term exposure to average PM2.5 ambient concentration
      was associated with approximately 8% of lung cancer mortality. The underlying
      mechanisms of how PM contributes to lung carcinogenesis, however, remain to be
      elucidated. We have recently found that transition metals such as nickel and
      chromium and oxidative stress induced lipid peroxidation metabolites such as
      aldehydes can greatly inhibit nucleotide excision repair (NER) and enhance
      carcinogen-induced mutations. Because PM is rich in metal and aldehyde content
      and can induce oxidative stress, we tested the effect of PM on DNA repair
      capacity in cultured human lung cells using in vitro DNA repair synthesis and
      host cell reactivation assays. We found that PM greatly inhibits NER for
      ultraviolet (UV) light and benzo(a)pyrene diol epoxide (BPDE) induced DNA damage
      in human lung cells. We further demonstrated that PM exposure can significantly
      increase both spontaneous and UV-induced mutagenesis. These results together
      suggest that the carcinogenicity of PM may act through its combined effect on
      suppression of DNA repair and enhancement of DNA replication errors.

PMID- 18804181
TI  - Androgen action in the brain and spinal cord for the regulation of male sexual
      behaviors.
AB  - Circulating levels of androgens determine the sexual differentiation of the brain
      and spinal cord at a critical period. Although estradiol, which is converted from
      testosterone by aromatase action, can explain the cytological basis for the
      sexual dimorphism, androgen has its own regulatory mechanism to promote male
      specific behavior through receptors. The central nervous system (CNS) employs a
      sex-specific neuronal network involving peptides and steroids for the expression
      of the sexual phenotype. Elucidation of the molecular mechanism along with the
      neuroanatomical background should guide the development of novel
      pharmacotherapeutics for sexual behavior dysfunction.

PMID- 18804182
TI  - Antibody-based identification of cell surface antigens: targets for cancer
      therapy.
AB  - The identification of novel cell surface antigens present on tumor cells is
      crucial for developing new cancer therapies. Intact, viable cancer cells, which
      display cancer-restricted antigens in their native conformation and cellular
      context, provide a rich source of novel antigens. Antibody-based technologies are
      being used to probe the surface of intact cancer cells for cancer-specific
      antigen targets. In addition to identifying new proteins, these approaches are
      generating monoclonal antibodies (MAbs) to cancer-specific epitopes and
      nonprotein targets not amenable to genomics-based approaches. The multiple cell
      based approaches developing epitope-specific MAbs to cancer antigens is likely to
      usher in a new era of therapeutic MAb target discovery.

PMID- 18804183
TI  - Perception and recall of faces and facial expressions following temporal
      lobectomy.
AB  - The perception of and memory for faces, with or without emotional content, were
      studied in 43 patients with temporal lobe epilepsy who had undergone unilateral
      resection of the hippocampus and the amygdala and in 43 healthy participants for
      comparison. Each participant performed four tasks from the Florida Affect Battery
      (Facial Discrimination, Affect Discrimination, Affect Naming, Affect Selection)
      and two memory tasks (in one case of a face and in the other of a facial
      expression). Findings indicated that, although patients with unilateral temporal
      lobectomy (right or left) showed no difficulty in discriminating faces, they were
      not as good at remembering faces. Also, patients who had had a left temporal
      lobectomy showed impairment in discriminating facial expressions, in the memory
      of a facial expression and/or in naming facial expressions.

PMID- 18804184
TI  - Neuroimaging and cognitive changes during deja vu.
AB  - OBJECTIVE: The cause or the physiological role of deja vu (DV) in healthy people
      is unknown. The pathophysiology of DV-type epileptic aura is also unresolved.
      Here we describe a 22-year-old woman treated with deep brain stimulation (DBS) of
      the left internal globus pallidus for hemidystonia. At certain stimulation
      settings, DBS elicited reproducible episodes of DV. METHODS: Neuropsychological
      tests and single-photon-emission computed tomography (SPECT) were performed
      during DBS-evoked DV and during normal DBS stimulation without DV. RESULTS: SPECT
      during DBS-evoked DV revealed hyperperfusion of the right (contralateral to the
      electrode) hippocampus and other limbic structures. Neuropsychological
      examinations performed during several evoked DV episodes revealed disturbances in
      nonverbal memory. CONCLUSION: Our results confirm the role of mesiotemporal
      structures in the pathogenesis of DV. We hypothesize that individual neuroanatomy
      and disturbances in gamma oscillations or in the dopaminergic system played a
      role in DBS-elicited DV in our patient.

PMID- 18804185
TI  - Rapid effect of levetiracetam in a case of juvenile myoclonic epilepsy.

PMID- 18804186
TI  - Depression and anxiety in children and adolescents with epilepsy: prevalence,
      risk factors, and treatment.
AB  - Among the psychiatric comorbid conditions in children and adolescents with
      epilepsy, depression and anxiety disorders require further attention because they
      carry the risk of reduced quality of life and life-threatening complications
      (e.g., suicide). Research in recent years has shed light on both the prevalence
      of emotional problems in youth with epilepsy and the safety and efficacy of
      treatment options. A number of challenges exist in treating patients with
      epilepsy. This is particularly true when seizures are difficult to control and
      medication regimens are more complex. Some pharmaceutical options may provide
      assistance with both seizures and emotional distress, but care is needed when
      considering such treatment approaches. In addition, integration of mental health
      professionals into the care of patients is necessary when cases are complicated
      and risk factors are high. Thorough methods to accurately diagnose emotional
      conditions and regular monitoring of symptoms can help prevent serious problems
      that can negatively affect the success of children and adolescents in everyday
      life. Collaboration between disciplines offers the best hope for early
      identification and treatment of these conditions.

PMID- 18804187
TI  - Venom variation in hemostasis of the southern Pacific rattlesnake (Crotalus
      oreganus helleri): isolation of hellerase.
AB  - Envenomations by the southern Pacific rattlesnake (Crotalus oreganus helleri) are
      the most common snakebite accidents in southern California. Intraspecies venom
      variation may lead to unresponsiveness to antivenom therapy. Even in a known
      species, venom toxins are recognized as diverse in conformity with
      interpopulational, seasonal, ontogenetic and individual factors. Five venoms of
      individual C. oreganus helleri located in Riverside and San Bernardino counties
      of southern California were studied for their variation in their hemostatic
      activity. The results demonstrated that Riverside 2 and San Bernardino 1 venoms
      presented the highest lethal activity without hemorrhagic activity. In contrast,
      San Bernardino 2 and 3 venoms had the highest hemorrhagic and fibrinolytic
      activities with low lethal and coagulant activities. Riverside 1, Riverside 2 and
      San Bernardino 1 venoms presented a significant thrombin-like activity. San
      Bernardino 2 and 3 venoms presented an insignificant thrombin-like activity. In
      relation to the fibrinolytic activity, San Bernardino 3 venom was the most active
      on fibrin plates, which was in turn neutralized by metal chelating inhibitors.
      These results demonstrate the differences amongst C. oreganus helleri venoms from
      close localities. A metalloproteinase, hellerase, was purified by anionic and
      cationic exchange chromatographies from San Bernardino 3 venom. Hellerase
      exhibited the ability to break fibrin clots in vitro, which can be of
      biomedically importance in the treatment of heart attacks and strokes.

PMID- 18804189
TI  - Genomic evolution in a virus under specific selection for host recognition.
AB  - Genetic variation in viral structural proteins is often explained by evolutionary
      escape of strong host defenses through processes such as immune evasion, host
      switching, and tissue tropism. An understanding of the mechanisms driving
      evolutionary change in virus surface proteins is key to designing effective
      intervention strategies to disease emergence. This study investigated the
      predictability of virus genomic evolution in response to highly specific
      differences in host receptor structure. The bacteriophage PhiX174 was evolved on
      three E. coli mutant hosts, each differing only by a single sugar group in the
      lipopolysaccharides, used for phage attachment. Large phage populations were used
      in order to maximize the amount of sequence space explored by mutation, and thus
      the potential for parallel evolution. Repeatability was assessed by genome
      sequencing of multiple isolates from endpoint populations and by fitness of the
      endpoint population relative to its ancestor. Evolutionary lines showed similar
      magnitudes of fitness increase between treatments. Only one mutation, occurring
      in the internal DNA pilot protein H, was completely repeatable, and it appeared
      to be a necessary stepping stone toward further adaptive change. Substitutions in
      the surface accessible major capsid protein F appeared to be involved in capsid
      stability rather than specific interactions with host receptors, suggesting that
      non-specific alterations to capsid structure could be an important component of
      adaptation to novel hosts. 33% of mutations were synonymous and showed evidence
      of selection on codon usage. Lastly, results supported previous findings that
      evolving populations of small ssDNA viruses may maintain relatively high levels
      of genetic variation.

PMID- 18804188
TI  - Endothelium as master regulator of organ development and growth.
AB  - Development of the vasculature is one of the earliest events during
      embryogenesis, preceding organ formation. Organogenesis requires a complex set of
      paracrine signals between the vasculature and the developing nonvascular tissues
      to support differentiation and organ growth. However, the role of endothelium in
      controlling organ growth and, ultimately, size is little-understood. In this
      review, we summarize new data regarding the endothelium function in order to
      provide a more comprehensive understanding of the communication between the
      endothelium and the organ's tissue.

PMID- 18804190
TI  - Therapeutic effects of triptolide on interleukin-10 gene-deficient mice with
      colitis.
AB  - BACKGROUND: Triptolide, the principal active ingredient in the extract of Chinese
      herb Tripterygium wilfordii Hook , has both anti-inflammatory and
      immunomodulatory activities. However, the potential therapeutic role of
      triptolide in IBD was still unknown. Interleukin-10 deficient mice, a well
      characterized experimental model of inflammatory bowel disease, spontaneously
      developed a Th1 T cell-mediated colitis with many similarities to Crohn's
      disease. This study was designed to investigate the therapeutic effect of
      triptolide on the chronic colitis in IL-10-/- mice. METHODS: Triptolide was
      intraperitoneally administrated every another day for 8 weeks to IL-10-/- mice.
      The gross and histological appearances of the colon, the level of inflammatory
      mediators and transcription factor activation in the colon were evaluated and
      compared with the control group. RESULTS: The 8-week administration of triptolide
      resulted in a significant decrease in the severity of colitis, together with
      lower production of TNF-alpha ,IFN-gamma and IL-4 in colon. The level of serum
      amyloid A was decreased in triptolide-treated mice. Gene expressions of IL-12 and
      IL-23 in colon were also downregulated after treatment. Furthermore,
      administration of triptolide markedly reduced NF-small ka, CyrillicB activation
      in colon mucosa of IL-10-/- mice. CONCLUSIONS: The efficacy of tritpolide
      treatment for the reduction of intestinal inflammation in IL-10-/- mice is a
      result of both anti-inflammatory and immunosuppressive activity. Triptolide holds
      significant potential for clinical applications for CD treatment.

PMID- 18804191
TI  - Coexpression of acidic fibroblast growth factor enhances specific productivity
      and antibody titers in transiently transfected HEK293 cells.
AB  - Recombinant proteins are of great commercial and scientific interest. However,
      most current production methods using mammalian cells involve the time- and labor
      intensive step of creating stable cell lines. Although production methods based
      on transient gene expression could offer a significant improvement, transient
      transfection is currently still limited by low titers and low specific
      productivity compared to stable cell lines. To overcome these bottlenecks, we
      have explored the use of various growth factors to enhance specific productivity
      and titers in the context of transient gene expression. For that purpose, several
      growth factors were cloned and screened for their effect on transient gene
      expression in HEK293E and CHO-DG44 cells. In particular, acidic fibroblast growth
      factor (aFGF) was able to increase specific productivity by 60% and recombinant
      protein titers by 80% in HEK293E cells, while FGF9 increased titers by 250% in
      CHO-DG44 cells.

PMID- 18804192
TI  - The corrective effects of warning on false memories in the DRM paradigm are
      limited to full attention conditions.
AB  - Effects of attention control and forewarning on the activation and monitoring of
      experimentally induced false memories in the Deese/Roediger-McDermott paradigm
      were investigated in a young adult sample (N=77). We found that reducing the
      degree of attention during encoding led to a decrease in veridical recall and an
      increase in non-presented critical lure intrusions. This effect could not be
      counteracted by a forewarning instruction. However, these findings did not emerge
      in a (retrieval supportive) recognition task. It seems that divided attention
      increases false recall when attention control and forewarning have to compete for
      limited cognitive resources in a generative free recall as opposed to a retrieval
      supportive recognition task. Forewarning instructions do not always protect young
      adults against experimentally induced false memories.

PMID- 18804193
TI  - Sequential effects within a short foreperiod context: evidence for the
      conditioning account of temporal preparation.
AB  - Responses to an imperative stimulus (IS) are especially fast when they are
      preceded by a warning signal (WS). When the interval between WS and IS (the
      foreperiod, FP) is variable, reaction time (RT) is not only influenced by the
      current FP but also by the FP of the preceding trial. These sequential effects
      have recently been proposed to originate from a trace conditioning process, in
      which the individuals learn the temporal WS-IS relationship in a trial-by-trial
      manner. Research has shown that trace conditioning is maximal when the temporal
      interval between the conditioned and unconditioned stimulus is between 0.25 and
      0.60s. Consequently, one would predict that sequential effects occur especially
      within short FP contexts. However, this prediction is contradicted by Karlin
      [Karlin, L. (1959). Reaction time as a function of foreperiod duration and
      variability. Journal of Experimental Psychology, 58, 185-191] who did not observe
      the typical sequential effects with short FPs. To investigate temporal
      preparation for short FPs, three experiments were conducted, examining the
      sequential FP effect comparably for short and long FP-sets (Experiment 1),
      assessing the influence of catch trials (Experiment 2) and the case of a very
      dense FP-range (Experiment 3) on sequential FP effects. The results provide
      strong evidence for sequential effects within a short FP context and thus support
      the trace conditioning account of temporal preparation.

PMID- 18804194
TI  - Photoemission and absorption spectroscopy of carbon nanotube interfacial
      interaction.
AB  - Element-specific techniques including near edge X-ray absorption fine structure,
      extended X-ray absorption fine structure and X-ray photoemission spectroscopy for
      the characterization of the carbon nanotube interfacial interactions are
      reviewed. These techniques involve soft and hard X-rays from the laboratory-based
      and synchrotron radiation facilities. The results provided information of how the
      nano-particles of catalysts are involved in the initial stage of nanotube growth,
      the nanotube chemical properties after purification, functionalization, doping
      and composite formation.

PMID- 18804196
TI  - [Physiological bases and practices in vestibular rehabilitation].
AB  - Today vestibular rehabilitation has an important place in managing chronic
      vertigo and balance disorders. It is based on the principle of completing and/or
      accelerating the physiological processes of central compensation when, for one
      reason or another, these processes cannot be put in place to offset a vestibular
      deficit. From a practical point of view, this compensation uses and reinforces
      the compensatory strategies that are activated spontaneously, but incompletely,
      by the patient, i.e., adaptation, substitution, and habituation strategies. These
      techniques call on physical exercises and/or instrumental techniques that should
      be adapted to the patient based on the clinical workup and paraclinical
      instrumental assessment done by a trained specialist, which will identify side
      involved, the central or peripheral character of the disorder, the current degree
      of central compensation, and the patient's ability to use various sensory inputs.
      In addition to the acute vestibular deficits, the best indications are chronic
      dizziness stemming from unilateral or bilateral peripheral vestibular deficit, or
      a nonprogressive central but stabilized deficit, with incomplete compensation,
      whatever the patient's age. Measures should be applied to the disorder as the
      patient describes it, with the number of sessions specified.

PMID- 18804195
TI  - [Update on vitamin D and evaluation of vitamin D status].
AB  - Knowledge about vitamin D has greatly improved during the last few years. Vitamin
      D cannot any more be considered as exclusively necessary to prevent
      ricket/osteomalacia. Its role in the prevention of some osteoporotic fractures in
      the elderly (in association with calcium nutrition) is now well demonstrated and
      many epidemiologic and laboratory data argue for a role in the prevention of
      several diseases or anomalies (cancer, auto-immune diseases, cardiovascular
      events, sarcopenia...). A few intervention studies confirming some of these
      effects also exist. Vitamin D status can easily be assessed by measuring serum 25
      hydroxy vitamin D (25OHD) level. However, many experts have claimed that the
      population-based reference values for 25OHD are too low and that the cut-off
      value below which vitamin D insufficiency can be present is somewhere between 20
      and 40 ng/mL with a clear tendency to target values above 30 ng/mL (75 nmol/L).
      The main consequences are that vitamin D insufficiency is highly frequent whereas
      the currently recommended supplementation doses are not sufficient.

PMID- 18804197
TI  - Potential biomarkers of human salivary function: a modified proteomic approach.
AB  - OBJECTIVE: In previous studies, we defined groups of subjects with opposite
      salivary function. Group membership was associated with clinically relevant
      outcomes. High aggregation-adherence (HAA) groups showed lower levels of caries,
      supragingival plaque, total streptococci, and Tannerella forsythensis than low
      high aggregation-adherence (LAA) groups. In this study, we used a proteomic
      approach to search for biomarkers which could be useful as risk indicators for
      those outcomes. DESIGN: Clarified resting whole saliva from each of 41 HAA and
      LAA subjects was separated by preparative isoelectric focusing. Fractions showing
      the most distinctive protein profiles were pooled into four sets (pI 3-3.5, pI 4
      4.7, pI 5.7-7.7, pI 10-11.5). Each pool then was compared by SDS-PAGE. Image
      analysis software was used to quantify matched bands. Partial least squares
      analysis (PLS) was used to determine which of the 65 bands from all four pools
      were the best predictors of group membership, caries, total plaque, total
      streptococci, and T. forsythensis counts. Those bands were identified by mass
      spectroscopy (MS-MS). RESULTS: Two bands consistently were strong predictors in
      separate PLS analyses of each outcome variable. In follow-up univariate analyses,
      those bands showed the strongest significant differences between the HAA and LAA
      groups. They also showed significant inverse correlations with caries and all the
      microbiological variables. MSMS identified those bands as statherin, and a
      truncated cystatin S missing the first eight N-terminal amino acids. CONCLUSIONS:
      Levels of statherin and truncated cystatin S may be potential risk indicators for
      the development of caries and other oral diseases.

PMID- 18804198
TI  - The psychometric properties of the Finnish Young Schema Questionnaire in chronic
      pain patients and a non-clinical sample.
AB  - We investigated the latent factor structure of the Finnish Young Schema
      Questionnaire (YSQ-S2-extended; short form) in samples of chronic pain patients
      (n=271) and controls (n=331) with confirmatory factor analysis (CFA). The data in
      the total sample supported the 18-factor structure as hypothesized by Young, J.
      E., Klosko, J., & Weishaar, M. E. (2003). Schema therapy: A practitioner's guide.
      New York: Guilford Press. The diagonally weighted least squares estimation method
      gave repeatable parameter estimates in successive confirmatory factor analyses
      (CFA). The internal consistency of the YSQ-S2-extended was adequate to high in
      both samples and the groups showed equal goodness-of-fit statistics in CFA. This
      study consisted of the oldest population so far (mean age 47 years) and supported
      the use of the Finnish version of the YSQ-S2-extended in clinical practice.

PMID- 18804199
TI  - Sudden gains in group cognitive-behavioral therapy for panic disorder.
AB  - The current study investigates sudden gains (rapid symptom reduction) in group
      cognitive-behavioral therapy for panic disorder. Sudden gains occurring after
      session 2 of treatment predicted overall symptom reduction at treatment
      termination and some changes in cognitive biases. Meanwhile, sudden gains
      occurring immediately following session 1 were not associated with symptom
      reduction or cognitive change. Together, this research points to the importance
      of examining sudden gains across the entire span of treatment, as well as the
      potential role of sudden gains in recovery from panic disorder.

PMID- 18804200
TI  - Heterogeneity of depolymerized heparin SEC fractions: to pool or not to pool?
AB  - In the structural analysis of heparin and heparan sulfate, it is customary to
      combine or pool like-sized fractions obtained by size-exclusion chromatography
      (SEC) of enzymatically derived heparin oligosaccharides. In this study, we
      examine the heterogeneity of preparative-scale SEC fractions obtained from
      enzymatic digests of porcine intestinal mucosa heparin. Each fraction was
      profiled by capillary electrophoresis with UV detection (CE-UV) using a 60 mM
      formic acid running buffer at pH 3.43. Differences in the composition and
      relative concentration of components of the SEC fractions were observed for
      disaccharides and larger oligosaccharides. The heterogeneity of the fractions
      becomes more pronounced when heparin is digested using a heparin lyase cocktail.
      The heterogeneity of preparative SEC fractions was further investigated by
      reversed-phase ion-pairing ultraperformance liquid chromatography coupled with
      mass spectrometry (RPIP-UPLC-MS) using the ion-pairing reagent, tributylamine
      (Bu(3)N). Our results suggest that preliminary profiling of preparative SEC
      fractions prior to pooling may simplify efforts to identify and/or isolate rare
      structures.

PMID- 18804201
TI  - Synthesis of the trisaccharide repeating unit related to Klebsiella 012 serotype.
AB  - Synthesis of the trisaccharide, allyl alpha-l-rhamnopyranosyl-(1->3)-2-acetamido
      2-deoxy-beta-d-glucopyranosyl-(1->4)-alpha-l-rhamnopyranoside related to O-chain
      glycans isolated from the deaminated LPSs of Klebsiella pneumoniae serotype 012,
      was achieved through condensation of suitably synthesized disaccharide, allyl 4,6
      O-benzylidene-2-deoxy-2-phthalimido-beta-d-glucopyranosyl-(1->4)-2,3-di-O-benzoyl
      alpha-l-rhamnopyranoside and donor, ethyl 2,3,4-tri-O-acetyl-1-thio alpha-l
      rhamnopyranoside starting from l-rhamnose and d-glucosamine hydrochloride. The
      trisaccharide can be utilized for the synthesis of neoglycoconjugates for use as
      a synthetic vaccine by coupling it with a suitable protein after deprotection.
      Various regio- and stereoselective protecting group strategies have been
      carefully considered, as protecting groups can influence the reactivity of the
      electrophile and nucleophile in glycosylation reactions on the basis of steric
      and electronic requirements.

PMID- 18804202
TI  - Visual homing in the absence of feature-based landmark information.
AB  - Despite that fact that landmarks play a prominent role in human navigation,
      experimental evidence on how landmarks are selected and defined by human
      navigators remains elusive. Indeed, the concept of a 'landmark' is itself not
      entirely clear. In everyday language, the term landmark refers to salient,
      distinguishable, and usually nameable objects, rendering the problem of landmark
      recognition a special case of the general object recognition problem. In
      contrast, in the insect and robot literature, this notion of landmarks is often
      replaced by the "local position information" [e.g., Trullier, O., Wiener, S.,
      Berthoz, A., & Meyer, J.-A. (1997). Biologically based artificial navigation
      systems: Review and prospects. Progress in Neurobiology, 51, 483-544], referring
      to the entire set of sensor readings obtained at one location. This set may then
      serve as a characteristic of the particular location. Honey bees have been shown
      to base place recognition and homing on a snapshot-like memory of the place's
      visual environment, not on the distances to recognized objects [Cartwright, B., &
      Collett, T. (1983). Landmark learning in bees. Experiments and models. Journal of
      Comparative Physiology A, 151, 521-543]. A number of theoretical models of
      snapshot-based homing [e.g., Franz, M., Scholkopf, B., Mallot, H. A., Bulthoff,
      H. H. (1998). Where did I take that snapshot? Scene-based homing by image
      matching. Biological Cybernetics, 79, 191-202; Vardy, A., & Moller, R. (2005).
      Biologically plausible visual homing methods based on optical flow techniques.
      Connection Science, 17, 47-89] predict that the accuracy of snapshot-based homing
      should depend on image contrast. For rodent hippocampal place fields, models have
      been developed using additional image information such as three-dimensional depth
      and allocentric orientations (e.g., room axes) and are thus less sensitive to
      image contrast and noise [e.g. Barry, C., Lever, C., Hayman, R., Hartley, T.,
      Burton, S., O'Keefe, J., et al. (2006). The boundary vector cell model of place
      cell firing and spatial memory. Reviews in the Neurosciences, 17, 71-79]. Here,
      we study human visual homing in a virtual environment void of objects and readily
      detected image features. The environment was a circular room with a homogenous
      colour gradient covering the wall and uniform floor and ceiling. Subjects were
      able to approach remembered places. Accuracy decreased with colour gradient
      modulation and room size, in qualitative agreement with the snapshot model but
      not with other models of place recognition. We conclude that human memory for
      places can make use of a snapshot algorithm.

PMID- 18804203
TI  - Applying stochastic resonance to magnify mu and beta wave suppression.
AB  - The goal was to test whether band-limited sensory noises with adequate
      amplitudes, by the principle of stochastic resonance, could enhance mu and beta
      wave suppressions. Scalp EEG was recorded while the subject performed thumb
      movements in the presence of vibratory noises applied to thenar belly or thumb
      tip. Seven subjects without clear mu or beta wave suppression in the absence of
      the mechanical stimuli were recruited. The results showed that when the stimuli
      were applied to the thenar belly, both mu and beta wave suppressions were
      enhanced in a bell-shaped trend (the characteristics of stochastic resonance) in
      four subjects.

PMID- 18804204
TI  - Women with cancer undergoing ART for fertility preservation: a cohort study of
      their response to exogenous gonadotropins.
AB  - Cancer patients produce similar numbers of oocytes after ovarian hyperstimulation
      compared with age-matched infertile controls, suggesting that malignancy does not
      adversely affect ovarian response.

PMID- 18804205
TI  - Melatonin and the ovary: physiological and pathophysiological implications.
AB  - OBJECTIVE: To summarize the role of melatonin in the physiology and
      pathophysiology of the ovary. DESIGN: Review of literature. SETTING: University
      Health Science Center. RESULT(S): Melatonin plays an essential role in the
      pathogenesis of many reproductive processes. Human preovulatory follicular fluid
      (FF) contains higher concentrations of melatonin than does plasma, and melatonin
      receptors are present in ovarian granulosa cells (GC). Melatonin has been shown
      to have direct effects on ovarian function. Reactive oxygen species and apoptosis
      are involved in a number of reproductive events including folliculogenesis,
      follicular atresia, ovulation, oocyte maturation, and corpus luteum (CL)
      formation. Melatonin and its metabolites are powerful antioxidants; the primitive
      and primary function of melatonin may be its actions as a receptor-independent
      free radical scavenger and a broad-spectrum antioxidant. A large amount of
      scientific evidence supports a local role of melatonin in the human reproductive
      processes. The indole also has potential roles in the pathophysiology of
      endometriosis, polycystic ovary syndrome (PCOS), and premature ovarian failure
      (POF). CONCLUSION(S): We summarize the current understanding of melatonin's
      essential functions in the human ovary. Melatonin could become an important
      medication for improving ovarian function and oocyte quality, and open new
      opportunities for the management of several ovarian diseases.

PMID- 18804206
TI  - The effect of early fetal losses on twin assisted-conception pregnancy outcomes.
AB  - OBJECTIVE: To evaluate the effect of first trimester fetal losses on twin births
      from assisted reproductive technology (ART). DESIGN: Historical cohort study.
      SETTING: Clinic-based data. PATIENT(S): The study population included 9,036 twin
      pregnancies of >or=22 weeks' gestation in the 2005 Society for Assisted
      Reproductive Technology Clinic Outcomes Reporting System database, categorized by
      the presence of three versus two fetal heartbeats on early ultrasound.
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Length of gestation and
      birthweight. Adjusted odds ratios (AORs) were calculated with the group with two
      fetal heartbeats on early ultrasound as the reference. RESULT(S): Increased odds
      with three fetal heartbeats included <32 weeks, 32-36 weeks, and <37 weeks (AORs
      1.47, 1.28, and 1.35, respectively) and very low birthweight (<1,500 g),
      moderately low birthweight (1,500-2,499 g), and low birthweight (<2,500 g) (AORs
      1.69, 1.38, and 1.47, respectively). Significantly decreased odds included term
      birth (>or=37 weeks) and nonlow birthweight (>or=2,500 g) (AORs 0.74 and 0.68).
      CONCLUSION(S): Early fetal loss in assisted-conception pregnancies that result in
      a twin live birth is associated with significantly increased risks for lowered
      birthweight and shortened gestation. Because first-trimester multiple fetal
      heartbeats are more common in ART pregnancies, this factor may help explain the
      greater risk for reduced birthweight and shorter gestations observed in this
      population.

PMID- 18804207
TI  - A prospective randomized controlled trial of preimplantation genetic screening in
      the "good prognosis" patient.
AB  - OBJECTIVE: To determine whether the routine use of preimplantation genetic
      screening (PGS) in "good prognosis" women improves in vitro fertilization (IVF)
      cycle outcome. DESIGN: Randomized, controlled, prospective clinical study.
      SETTING: Private infertility clinic. PATIENT(S): Infertile women predicted to
      have a good prognosis as defined by: age <39 years, normal ovarian reserve, body
      mass index <30 kg/m(2), presence of ejaculated sperm, normal uterus, <or=2
      previous failed IVF cycles. INTERVENTION(S): Patients were randomized to the PGS
      group or the control group on day 3 after oocyte retrieval; 23 women underwent
      blastomere biopsy on day 3 after fertilization (PGS group), and 24 women
      underwent routine IVF (control group). All embryos were transferred on day 5 or 6
      after fertilization. MAIN OUTCOME MEASURE(S): Pregnancy, implantation, multiple
      gestation, and live birth rates. RESULT(S): No statistically significant
      differences were found between the PGS and control groups with respect to
      clinical pregnancy rate (52.4% versus 72.7%). However, the embryo implantation
      rate was statistically significantly lower for the PGS group (31.7% versus 62.3%)
      as were the live birth rate (28.6% versus 68.2%) and the multiple birth rate
      (9.1% versus 46.7%). CONCLUSION(S): In a "good prognosis" population of women,
      PGS does not appear to improve pregnancy, implantation, or live birth rates.

PMID- 18804208
TI  - Primary hyperparathyroidism in pregnancy.
AB  - OBJECTIVE: To determine the management of a patient with primary
      hyperparathyroidism and the obstetric and neonatologic outcome. DESIGN: Case
      report. SETTING: University hospital of Udine, Italy. PATIENT(S): A 32-year-old
      black pregnant woman with primary hyperparathyroidism. INTERVENTION(S):
      Hospitalization with observation, nuclear magnetic resonance of the neck, and
      right parathyroidectomy of the patient in the 15th week of gestation (WG).
      Monitoring during pregnancy until the delivery. MAIN OUTCOME MEASURE(S):
      Intrauterine pregnancy preservation and maternal and fetal morbidity and
      mortality. RESULT(S): After surgery, laboratory and clinical findings remained
      constant. The fetus' well-being until the delivery was performed with
      cardiotocography (CTG) and echographic monitoring. Symmetric intrauterine growth
      restriction was discovered at 37 WG. Cesarean section was performed at 38 +/- 2
      WG owing to the CTG trace. CONCLUSION(S): Nuclear magnetic resonance of the neck
      in this case was the determining diagnostic exam. Parathyroidectomy, during the
      second trimester, is the therapeutic gold standard, especially in cases of severe
      hypercalcemia (>12 mg/dL).

PMID- 18804209
TI  - Increased levels of endothelial microparticles CD144 (VE-Cadherin) positives in
      type 2 diabetic patients with coronary noncalcified plaques evaluated by
      multidetector computed tomography (MDCT).
AB  - OBJECTIVE: The combination of both morphological and cellular markers of
      subclinical atherosclerosis, in addition to conventional risk factors, may help
      to improve cardiovascular prevention in type 2 diabetic patients. The aim of our
      cross-sectional study was to evidence a putative increase in endothelial (EMP) or
      platelet (PMP) microparticles, in type 2 diabetic patients with coronary
      noncalcified plaques detected by multidetector CT (MDCT). METHODS AND RESULTS:
      Microparticles and coronary MDCT were assessed in 56 type 2 diabetic patients
      with different cardiovascular risk levels. Both EMP (r=0.35, p=0.022) and PMP
      (rho=0.34, p=0.022) were correlated with hsCRP. EMP were elevated in patients
      with acute coronary syndromes (p=0.034). EMP count was significantly higher in
      the presence of noncalcified diseased segments (p=0.01). By contrast, there was
      no association between hsCRP and noncalcified atheroma. This increase in EMP in
      noncalcified diseased segment carriers remained borderline significant after
      adjustment for coronary heart disease and hsCRP. Conversely, there was no
      association of PMP count with noncalcified diseased segments and no difference in
      PMP count between patients with and without acute coronary syndrome. No
      significant association between either EMP and PMP counts and mixed or calcified
      diseased segments was observed. CONCLUSIONS: We report for the first time an
      association between plasma EMP-CD144+ and coronary noncalcified plaques assessed
      by MDCT in a population of type 2 diabetic patients. EMP might be used as a
      surrogate marker of unstable plaques, and might help to improve cardiovascular
      prediction in diabetic patients with intermediate risk.

PMID- 18804210
TI  - Smoking, inflammatory patterns and postprandial hypertriglyceridemia.
AB  - BACKGROUND: Smoking is associated with increased postprandial
      hypertriglyceridemia (PPT). Inflammation and insulin resistance are potential
      "drivers" for this phenomenon. We tested whether inflammatory patterns and/or
      insulin resistance explain the effect of smoking on PPT. METHODS AND RESULTS: Men
      and women in the NHLBI Genetics of Lipid-Lowering Drugs and Diet Network (GOLDN)
      study (n=1036, age 49+/-16y) were included. Each participant was asked to suspend
      use of lipid-lowering drugs for 3 weeks and was given a high-fat milkshake (83%
      fat and 700kcal/m(2)). Triglyceride concentrations at 0, 3.5 and 6h after the fat
      load were measured. Inflammatory markers were measured at baseline. Principal
      component analysis was used to derive inflammatory patterns from individual
      inflammatory markers (hsCRP, IL2 soluble receptor-alpha, IL6, TNF-alpha and
      MCP1). Insulin resistance (IR) was estimated using the HOMA equation. Repeated
      measures-ANOVA was used for analyses. Two inflammatory patterns, namely CRP-IL6
      pattern and MCP1-TNF-alpha pattern, were derived. We found significant main
      (smoking and time) and interaction (smokingxtime) effects (P<0.01) for
      triglycerides. The multivariate-adjusted triglyceride (mg/dL) concentrations
      (mean+/-S.E.M.) for never, past and current smokers were 127.38+/-1.04, 119.82+/
      1.05 and 134.92+/-1.08 at 0h; 229.42+/-1.04, 238.39+/-1.05 and 293.94+/-1.08 at
      3.5h; and 194.63+/-1.04, 208.38+/-1.05 and 248.27+/-1.08 at 6h after the fat
      load, respectively. Smoking remained significant after adjusting for HOMA-IR
      and/or inflammatory patterns which showed independent associations with PPT
      (P<0.05). CONCLUSIONS: These data confirm impaired metabolism of fat among
      smokers and suggest that mechanisms other than inflammation or insulin resistance
      may explain the observed hypertriglyceridemia among smokers.

PMID- 18804211
TI  - Analysis of indandione anticoagulant rodenticides in animal liver by eluent
      generator reagent free ion chromatography coupled with electrospray mass
      spectrometry.
AB  - A novel analytical method has been developed for simultaneous determination of
      four indandione anticoagulant rodenticides (diphacinone, chlorophacinone, pindone
      and valone) in animal liver tissues by eluent generator reagent free ion
      chromatography coupled with electrospray ionization mass spectrometry (RFIC-ESI
      MS). After the rodenticides were extracted from homogenized animal liver tissues
      with methanol-acetonitrile (10/90, v/v), the extracts were subjected to a solid
      phase extraction (SPE) process using Oasis HLB cartridges. The IC separation was
      carried out on an IonPac AS11 analytical column (250 mm x 4.0 mm) using 10%
      methanol in a gradient of KOH solution at a constant flow rate of 1.0 mL/min. The
      objective compounds were ionized by negative ion pneumatically assisted
      electrospray and detected in the selected ion monitoring (SIM) mode. Warfarin was
      applied as an internal standard (IS) for the compensation of the losses in the
      course of sample processing and the sensitivity drift of the detector, linear
      calibration functions were calculated for all analytes. The relative average
      recoveries of the objective compounds spiked in animal liver tissues were between
      83.4 and 104.9%. The limits of quantification (LOQs) were 0.2-1.0 ng/g for them.
      Within-day and day-to-day relative standard deviations (RSDs) were less than 10.4
      and 13.3%, respectively. It was confirmed that this method could be used in a
      toxicological analysis. The coupling of IC to MS provided a new analytical tool
      to the analysts faced with the requirement of separating and analyzing indandione
      rodenticides in animal livers.

PMID- 18804212
TI  - Determination of trace food-derived hazardous compounds in Chinese cooked foods
      using solid-phase extraction and gas chromatography coupled to triple quadrupole
      mass spectrometry.
AB  - Gas chromatography coupled to tandem mass spectrometry (GC-MS/MS) with a triple
      quadrupole analyzer (QqQ) was applied for the first time to the determination of
      trace food-derived hazardous compounds in food samples. Thirteen heterocyclic
      amines were confirmed and quantified by the developed sensitive method. The
      method includes a solid-phase extraction procedure with a polystyrene copolymer
      cartridge (LiChrolut EN), followed by a derivatization reaction with N,N
      dimethylformamide di-tert-butylacetal. Analyses were performed by gas
      chromatography with triple quadrupole mass spectrometry in the electron impact
      mode. The MS/MS fragmentation pathway of derived heterocyclic amines was studied
      and the differences of fragmentation characteristics were used successively to
      distinguish the isomers in absence of chemical standards. The excellent
      selectivity and sensitivity achieved in multiple reaction monitoring mode allowed
      us satisfactory quantitation and confirmation. The limits of quantitation of the
      method for these compounds ranged from 0.12 to 0.48ng/g of sample. The method
      developed was applied to the analysis of Chinese cooked foods, and the results
      demonstrated the potentiality of the GC-MS/MS method for the analysis of trace
      food-derived hazardous compounds in complex food matrices such as meat samples.

PMID- 18804213
TI  - Rapid and direct determination of glyphosate and aminomethylphosphonic acid in
      water using anion-exchange chromatography with coulometric detection.
AB  - A simple, rapid, and low-cost coulometric method for direct detection of
      glyphosate and aminomethylphosphonic acid (AMPA) in water samples using anion
      exchange chromatography and coulometric detection with copper electrode is
      presented. Under optimized conditions, the limits of detection (LODs) (S/N=3)
      were 0.038microgml(-1) for glyphosate and 0.24microgml(-1) for AMPA, without any
      preconcentration method. The calibration curves were linear and presented an
      excellent correlation coefficient. The method was successfully applied to the
      determination of glyphosate and AMPA in water samples without any kind of
      extraction, clean-up, or preconcentration step. No interferent was found in the
      water, like this, the recovery was, practically, 100%.

PMID- 18804214
TI  - Mechanical derivation of the Wenzel and Cassie equations using a statistical
      interpretation of drop dispensation.
AB  - The global mechanical equilibrium condition of a liquid on a rough and chemically
      heterogeneous surface was derived for three-dimensional situations from a
      statistical outlook of dispensation of many drops and the assumption of local
      mechanical equilibrium. Unlike the conventional thermodynamic derivations from
      variational methods, the current proof is based on vector algebra rather than
      differential geometry. The mechanics-based derivation becomes less intricate
      although the minimum energy condition is not established. An effective contact
      angle is computed from the directional sampling of three-phase lines after local
      drop dispensations. The final expression is a combined mechanical version of the
      Wenzel and Cassie equations.

PMID- 18804215
TI  - Newborn sickle cell screening in a region of Western New York State.
AB  - OBJECTIVES: To assess local trends in the incidence of sickle cell disease (SCD)
      and hemoglobin (Hb) S trait. Hemoglobinopathy clinic follow-up and cohort
      mortality rates were also evaluated. STUDY DESIGN: A longstanding newborn
      hemoglobinopathy screening program was reviewed. Incidence rates were computed
      with information from a confidential database, specialty clinic/hospital data,
      and local birth statistics. RESULTS: Over 27 years, the incidence of Hb SS in
      live black births was 0.163% or 1 in 615. Over 18 years, the incidence of Hb AS
      was 8.5% or 1 in 11.8. No significant differences in the incidence of Hb SS, Hb
      AS, and the S allele were found over time. Specialty clinic follow-up improved.
      Death before age 18 years was documented for 6 SCD cases (2.8%; mortality rate of
      0.23 per 100 patient years). CONCLUSIONS: Local screening activities may have had
      an impact on participation in specialized SCD care and the disease-associated
      mortality rate. The incidence of Hb SS has remained unchanged over 27 years, and
      that of Hb S trait and the S allele has been unaffected in the last 18 years.
      Trait notification goals and approaches should be reevaluated.

PMID- 18804216
TI  - Smoking and metabolic control in adolescents with type 1 diabetes.
AB  - OBJECTIVE: To relate self-reported smoking frequency to metabolic control and
      other cardiovascular risk factors in adolescents with type 1 diabetes. STUDY
      DESIGN: In the multicenter Diabetes Patienten Verlaufsdokumentationssystem
      database from Germany and Austria, anonymized records on 27 561 patients < 20
      years of age with documented smoking status were available for analysis. RESULTS:
      Self-reported smoking was negligible in patients younger than 11 years (0.1%),
      increasing to 5% in 11- to 15-year-old patients, and 28.4% in the 15- to 20-year
      old age group. Multivariate analysis with adjustment for age, diabetes duration,
      sex, insulin therapy, and center differences, revealed that smokers had higher
      HbA1c-levels compared with non-smokers (9.1% vs 8.0%, P < .0001). Diastolic blood
      pressure was higher (68.2 vs 67.6 mm Hg, P < .0001), and the lipid profile was
      unfavorable in patients who smoke: Triglycerides and total cholesterol were
      higher and high-density lipoprotein-cholesterol was lower (all P < .0001).
      CONCLUSIONS: Smokers display significantly worse metabolic control and a higher
      cardiovascular risk profile. Although not attested in trials, we state that
      education about smoking, smoking prevention, and psychological help for smoking
      cessation should be an integral part of comprehensive pediatric care for
      adolescent patients with type 1 diabetes.

PMID- 18804217
TI  - Cerebral and splanchnic hemodynamics after duct ligation in very low birth weight
      infants.
AB  - OBJECTIVE: To describe mesenteric and cerebral blood flow velocities after
      surgical patent ductus arteriosus (PDA) closure in premature infants. STUDY
      DESIGN: We measured middle cerebral artery (MCA), celiac artery (CA), and
      superior mesenteric artery (SMA) Doppler ultrasound scanning blood flow velocity
      (BFV) preoperatively, 3 and 24 hours after ligation. RESULTS: We studied 32
      infants, with a mean (+/- SD) birthweight of 762 +/- 170 g and gestational age of
      25.6 +/- 1.4 weeks at a mean age of 34 +/- 13 days. Significant changes in end
      diastolic (EDV), average velocity (AV), and vascular resistance were measured in
      all 3 vessels by 3 hours. AV increased significantly in the CA and SMA within 3
      hours; however, no significant increase in MCA AV was found until 24 hours after
      surgery. CONCLUSION: PDA ligation significantly changes BFV in the MCA, CA, and
      SMA. In the MCA vascular tone is acutely modulated, with no change in AV at 3
      hours. In the CA and SMA, AV increases acutely after ligation. These different
      patterns of change in BFV suggest region-specific adaptation to surgical PDA
      closure.

PMID- 18804218
TI  - Bayesian adaptive non-inferiority with safety assessment: retrospective case
      study to highlight potential benefits and limitations of the approach.
AB  - Adaptive trial design applied to randomized clinical trials of psychiatric
      medicines offers the potential to make clinical trials more efficient. In the
      current analysis, we retrospectively applied Bayesian adaptive allocation methods
      to a case study in agitated patients with schizophrenia and related diseases. The
      original study used a randomized, double-blind, parallel design. The objective of
      this analysis was to demonstrate the potential benefits of Bayesian adaptive
      designs by shortening the study duration and therefore limiting patient exposure
      to ineffective placebo or an active comparator with a known side effect. Bayesian
      methods allowed us to fully leverage historical data along with data observed as
      the study was ongoing to calculate predictive probabilities of patient response
      to treatment without experiencing a specified side effect. Using the Bayesian
      adaptive approach would have required less than half the number of patients as
      the original study to draw the same conclusion. Sample size was reduced from 311
      to 156 patients, thereby decreasing the number of patients exposed to placebo
      from 54 to 30 and the number exposed to the active control with a known side
      effect from 126 to 60.

PMID- 18804219
TI  - Colocalization of ribonuclear inclusions with muscle blind like-proteins in a
      family with myotonic dystrophy type 2 associated with a short CCTG expansion.
AB  - Myotonic dystrophy type 2 (DM2) is an autosomal dominant multisystemic disorder
      caused by a CCTG repeat expansion in intron 1 of the zinc finger protein 9 (ZNF9)
      gene. We present a three first-degree relative Italian family (proband, his
      mother and his sister) with a mild DM2 phenotype associated with a short
      (CCTG)(100) expansion as far as regards the proband and his mother, while his
      sister shows larger expansion correlated to a more severe phenotype. FISH
      analysis with (CAGG)(5) probe demonstrated that nuclear foci of mutant RNA were
      present in the proband muscle and co-localized with muscleblind-like proteins,
      determining their sequestration in the nucleus. This is one of the smallest
      expansion reported and the shortest with the evidence of nuclear foci. These data
      contribute to the clinical and molecular correlation of ZNF9 gene short
      expansion.

PMID- 18804220
TI  - Association of ankle-brachial index level with stroke.
AB  - BACKGROUND: There are conflicting data on the relationship between peripheral
      arterial disease (PAD) as defined by an ankle-brachial index (ABI) of <0.9 and
      stroke risk, and these prior data have largely focused on a single race or
      gender. Furthermore, the association between subsequent ABIs above the
      established 0.9 threshold for PAD vs. stroke has not been studied. This study
      assessed stroke occurrence across the full spectrum of ABI values among a broad
      cohort of stroke survivors. METHODS: Data from the National Health and Nutrition
      Examination Survey from 1999-2004, a nationally representative sample of United
      States adults, were used to assess prevalence of PAD as evidenced by ABI of <0.9,
      and to simultaneously identify the independent associations of ABI levels (<0.90,
      0.90-0.99, 1.00-1.09, >1.3) with stroke prevalence. RESULTS: Among 6382 adults,
      4602 (72%) had full and complete data of which 277 (6%) reported stroke
      occurrence. Stroke survivors were older and more likely to have diabetes,
      hypertension, coronary artery disease, elevated blood pressure and
      glycohemoglobin, than non-stroke respondents. More subjects with ABI <0.9 vs. >
      or =0.9 had experienced a stroke (12.7% vs. 5.4%, p<0.001). Within the full ABI
      range, stroke presence rose with decreasing ABI (p=0.0013). After adjustment for
      potential confounders, only ABI <0.9 (OR 1.9, 95% CI=1.2-3.1) and 0.9-0.99 (OR
      2.3, 95% CI=1.4-3.6) compared with the referent group (1.10-1.29) were
      significantly associated with presence of stroke. CONCLUSIONS: Data from this
      nationally representative cohort support an independent relationship between
      established PAD and stroke occurrence, but also indicate that even borderline PAD
      is strongly linked to stroke.

PMID- 18804221
TI  - New immunosuppressive approaches: oral administration of CD3-specific antibody to
      treat autoimmunity.
AB  - One of the major goals for the immunotherapy of autoimmune diseases is the
      induction of regulatory T cells that mediate immunologic tolerance. Parenteral
      administration of anti-CD3 monoclonal antibody is an approved therapy for
      transplantation in humans and is effective in autoimmune diabetes. We have found
      that oral administration of anti-CD3 monoclonal antibody is biologically active
      in the gut and suppresses experimental autoimmune encephalomyelitis both prior to
      disease induction and at the height of disease. Oral anti-CD3 antibody acts by
      inducing a unique type of regulatory T cell characterized by latency-associated
      peptide (LAP) on its cell surface that functions in vivo and in vitro via TGF
      beta dependent mechanism. Orally delivered antibody would not have side effects
      including cytokine release syndromes, thus oral anti-CD3 antibody is clinically
      applicable for chronic therapy. These findings identify a novel and powerful
      immunologic approach that is widely applicable for the treatment of human
      autoimmune conditions.

PMID- 18804223
TI  - Sperm DNA damage and semen quality impairment after treatment with selective
      serotonin reuptake inhibitors detected using semen analysis and sperm chromatin
      structure assay.
AB  - PURPOSE: Semen parameters and sperm DNA were evaluated in patients receiving
      selective serotonin reuptake inhibitors. MATERIALS AND METHODS: Semen samples
      were obtained from 74 fertile, depressed men treated with selective serotonin
      reuptake inhibitors (group 1) and 44 healthy fertile volunteers who served as a
      control (group 2). Two semen analyses and physical examinations were completed in
      all participants. Sperm chromatin structure assay was used to detect sperm DNA
      fragmentation. RESULTS: The mean +/- SE total sperm count in patients receiving
      selective serotonin reuptake inhibitors and in normal subjects was 61.2 +/- 11.4
      million and 186.2 +/- 31.4 million, respectively (p = 0.001). Patients in group 1
      had a mean motility of 48.2% +/- 4.6%, which was significantly lower than the
      mean of 66.2% +/- 4.4% in normal controls (p = 0.01). Normal sperm morphology was
      detected in 14 patients (18.9%) and 23 controls (52.3%) (p = 0.001). Patients
      treated with selective serotonin reuptake inhibitors had a mean of 8.1% +/- 5.4%
      normal forms per ejaculate. A significant increase in the amount of denatured
      single strand DNA in total cellular DNA was found in patients treated with
      selective serotonin reuptake inhibitors compared with that in controls (43.2% +/-
      11.4% vs 21.4% +/- 10.6%, p = 0.01). Each semen analysis parameter significantly
      correlated with treatment duration. CONCLUSIONS: Selective serotonin reuptake
      inhibitors can impair semen quality and damage sperm DNA integrity. Further
      studies are needed to replicate our findings.

PMID- 18804224
TI  - Dynamic interaction involved in the tension-free vaginal tape obturator
      procedure.
AB  - PURPOSE: We explored the static and dynamic morphological characteristics of the
      tension-free vaginal tape obturator procedure by ultrasound cystourethrography.
      MATERIALS AND METHODS: From July 2005 to December 2006, 98 consecutive women who
      had undergone the tension-free vaginal tape obturator procedures alone or with
      concomitant pelvic surgery were evaluated. Preoperative and postoperative
      morphological assessments of lower urinary tract and tension-free vaginal tape
      obturator procedure tape were performed by introital ultrasound. RESULTS: The
      resting and straining bladder neck angles as well as the resting tape angle
      gradually increased postoperatively while the resting bladder neck distance and
      total urethral length decreased. The vector of the tension-free vaginal tape
      obturator procedure tape was significantly correlated with the resting tape
      distance (r = 0.55, p <0.01). The tension-free vaginal tape obturator procedure
      tape migrated distally with time but remained in the same position relative to
      the urethra (60th percentile). Concomitant pelvic surgery did not affect the
      position and motion of the bladder neck or tension-free vaginal tape obturator
      procedure tape except for mesh reinforcement anterior colporrhaphy in which the
      tape was displaced proximally. Postoperatively 5 types of urethral descent in
      relation to the tape during stress were seen. One type of vertical and 1 type of
      rotational urethral descent during straining were observed in women in whom
      surgery failed, while 2 other types of vertical and 1 of rotational descent were
      not associated with failure. CONCLUSIONS: The dynamic interaction between the
      tension-free vaginal tape obturator procedure tape and urethra depends on the
      proximity of the tape and the type of urethral descent.

PMID- 18804225
TI  - Pediatric ureteroscopic management of intrarenal calculi.
AB  - PURPOSE: Data addressing ureteroscopic management of intrarenal calculi in
      prepubertal children are limited. We reviewed our experience from January 2002
      through December 2007. MATERIALS AND METHODS: We retrospectively reviewed
      ureteroscopic procedures for intrarenal calculi in children younger than 14
      years. Stone-free status was determined with postoperative imaging. Multiple
      logistic regression analysis was used to assess the influence of preoperative
      factors on initial stone-free status and the need for additional procedures.
      RESULTS: Intrarenal calculi were managed ureteroscopically in 52 kidneys in 50
      children with a mean age of 7.9 years (range 1.2 to 13.6). Mean stone size was 8
      mm (range 1 to 16). Stone-free rate after a single ureteroscopic procedure was
      50% (25 of 50 patients) on initial postoperative imaging and 58% (29 of 50) with
      extended followup. Initial stone-free status was dependent on preoperative stone
      size (p = 0.005) but not stone location. Additional stone procedures were
      required in 18 upper tracts. Younger patient age (p = 0.04) and larger
      preoperative stone size (p = 0.002) were associated with the need for additional
      procedures. Additional procedures were required in more than half of the stones 6
      mm or larger but in no stone smaller than 6 mm. CONCLUSIONS: Ureteroscopy is a
      safe method for the treatment of intrarenal calculi in the prepubertal
      population. Our ureteroscopic stone-free rate for intrarenal stones is lower than
      that reported for ureteral stones. Parents should be informed that additional
      procedures will likely be required, especially in younger patients and those with
      stones larger than 6 mm.

PMID- 18804226
TI  - Microsurgical varicocelectomy for isolated asthenospermia.
AB  - PURPOSE: Varicocele represents the most common cause of male infertility, and
      most reports indicate that varicocelectomy has a beneficial effect on male
      fertility and pregnancy outcome. We evaluated the clinical outcomes of infertile
      couples with varicocele and isolated asthenospermia who chose to undergo
      varicocelectomy as well as those who chose not to undergo the procedure.
      MATERIALS AND METHODS: We performed a retrospective review of 118 consecutive
      infertile couples in whom the man presented with clinical varicocele and isolated
      asthenospermia (less than 50% motile sperm). All couples were presented with
      possible treatment options (observation, varicocelectomy, assisted reproductive
      technologies). The clinical characteristics and outcomes of 2 subgroups of men-
      those who elected to undergo surgery (varicocelectomy, 69) and those who did not
      (49)--were examined and compared. RESULTS: Mean male and female patient age,
      duration of infertility and baseline total motile sperm count were not
      significantly different in the control and surgery groups. The mean total motile
      sperm count increased significantly after varicocelectomy (29.6 million
      preoperatively vs 39.0 million postoperatively, p <0.05). The spontaneous
      pregnancy rate was significantly higher in the surgery group compared to the
      control group (65% vs 32%, respectively, p <0.01). The combined spontaneous and
      intrauterine insemination pregnancy rate was also significantly higher in the
      surgery group compared to the control group (74% vs 36%, respectively, p <0.01).
      Use of in vitro fertilization/intracytoplasmic sperm injection was significantly
      higher in the control group compared to the surgery group (32% vs 11%,
      respectively, p <0.05). CONCLUSIONS: Our data support the practice of
      varicocelectomy for the treatment of clinical varicocele and isolated
      asthenospermia.

PMID- 18804227
TI  - Diagnostic accuracy of an initial azoospermic reading compared with results of
      post-centrifugation semen analysis after vasectomy.
AB  - PURPOSE: Semen analysis is a common laboratory procedure but few data are
      available to support recommendations as to whether centrifugation is necessary in
      the post-vasectomy context. We evaluated the accuracy of a pre-centrifugation
      determination of azoospermia compared with post-centrifugation results. MATERIALS
      AND METHODS: We conducted a secondary analysis of data from 3,205 semen analyses
      performed during a randomized clinical trial of 2 vasectomy techniques--ligation
      and excision with fascial interposition vs ligation and excision without fascial
      interposition. We performed brief, initial microscopic examinations to categorize
      sperm numbers per high power field to decide whether centrifugation or dilution
      was needed before estimation of sperm concentration. For specimens initially
      categorized as azoospermic, we reviewed the post-centrifugation semen analysis
      results to estimate the accuracy of the initial finding. RESULTS: Of 2,104
      samples categorized as azoospermic before centrifugation, post-centrifugation
      analysis demonstrated that all but 4 (99.8%) were azoospermic or had a sperm
      concentration of less than 100,000 sperm per ml. Four samples from 1 study site
      had counts between 104,000 and 315,000 sperm per ml. Of 1,610 apparently
      azoospermic samples obtained at 10 weeks or later after vasectomy there were 12
      (0.7%) that had some motile sperm identified after centrifugation but the numbers
      of motile sperm were low (mean 1,124 motile sperm per ml, range 238 to 3,710).
      CONCLUSIONS: Microscopic examination of uncentrifuged specimens is a reliable
      method for identifying semen samples after vasectomy with more than 100,000 sperm
      per ml.

PMID- 18804228
TI  - Histological characterization of the urethral edges in patients who underwent
      bulbar anastomotic urethroplasty.
AB  - PURPOSE: Meticulous excision of the stricture and any associated spongiofibrosis
      is critical to the success of urethral reconstruction. However, normal urethral
      limits are determined during surgical reconstruction based on macroscopic
      appearance only. We evaluated structural changes of the presumed healthy urethral
      ends. MATERIALS AND METHODS: Samples were obtained from 29 patients with a mean
      age of 40 years who underwent end-to-end anastomotic urethroplasty. Suprapubic
      catheter drainage was performed for at least 30 days in 15 patients. After the
      urethral stricture was excised biopsy was performed of the proximal and distal
      healthy ends. Structural characterization was evaluated by staining histological
      sections with Masson's trichrome, Sirius red and Weigert's resorcin-fuchsin
      method. The control group consisted of 10 cadaver bulbar urethras. RESULTS: All
      samples of presumed normal urethral ends showed histological changes. Chronic and
      acute inflammatory reactions were the most common findings. In the proximal
      urethral end intense cellularity was found in 18 patients (62.1%). Fibroblast and
      inflammatory cells were most common and related to the lack of suprapubic
      cystostomy (p = 0.001). Between proximal urethral edges with and without a
      suprapubic urinary catheter the elastic fiber distribution and the ratio of
      collagen types III and I showed a significant change (p = 0.045 and <0.001,
      respectively). CONCLUSIONS: The supposedly healthy urethral ends of end-to-end
      anastomotic urethroplasty show structural changes. Urethral obstruction and its
      relief by suprapubic urinary drainage can affect extracellular matrix turnover
      regulation. Therefore, these changes can lead to urethral remodeling in the
      proximal bulbar urethra.

PMID- 18804229
TI  - Urinary symptoms before and after female urethral diverticulectomy--can we
      predict de novo stress urinary incontinence?
AB  - PURPOSE: We assessed preoperative and postoperative urinary symptoms, and
      determined risk factors for de novo stress urinary incontinence after
      transvaginal urethral diverticulectomy. MATERIALS AND METHODS: We reviewed the
      case records of 25 consecutive women who had transvaginal urethral
      diverticulectomy. Urinary symptoms were documented before and after surgery with
      a structured history and examination pro forma. Demographic, clinical and imaging
      parameters were reviewed to determine any association with preoperative and
      postoperative symptoms as well as possible risk factors for postoperative stress
      urinary incontinence. RESULTS: The most common presenting symptoms were urinary
      urgency and frequency (60%), and dyspareunia (56%). On physical examination the
      most common findings were a tender anterior vaginal wall mass (88%) and urethral
      discharge (40%). At a mean followup of 15.1 +/- 14.9 months (median 12) the rate
      of urgency-frequency symptoms and dyspareunia decreased significantly from 60% to
      16% and from 56% to 8%, respectively. All the patients who had urge incontinence
      were cured of this symptom after the operation. De novo stress urinary
      incontinence developed in 4 patients (16%) postoperatively, and it was mild and
      only necessitated surgical treatment in 1 patient. A diverticulum larger than 30
      mm and proximal urethral location were significant factors (p <0.05) for the
      development of de novo stress urinary incontinence. CONCLUSIONS: Irritative
      bladder symptoms are common in woman with urethral diverticulum and usually
      resolve after surgical excision. Stress urinary incontinence developed
      immediately after the operation, and had a significant association with a
      proximal urethral location and ultrasonically measured size greater than 30 mm.

PMID- 18804231
TI  - Race and socioeconomic status are independently associated with benign prostatic
      hyperplasia.
AB  - PURPOSE: Prostate enlargement is common as men age. However, differences in the
      diagnosis or treatment of clinical benign prostatic hyperplasia between black and
      white men remain poorly understood. We investigated racial differences in and
      surgical intervention for benign prostatic hyperplasia in a large and
      predominantly low income population. MATERIALS AND METHODS: Participants included
      21,949 men, of whom 79.8% were black and 20.2% were white, recruited from 60
      community health centers in the southeastern United States between 2002 and 2007.
      Benign prostatic hyperplasia, surgical intervention for benign prostatic
      hyperplasia, and economic and demographic indexes, eg education, household
      income, health insurance and marital status, were determined by an interview in
      person. Logistic regression was used to summarize the association between race
      and benign prostatic hyperplasia while controlling for health care access and
      socioeconomic status. RESULTS: Black men were approximately half as likely to
      report a benign prostatic hyperplasia diagnosis compared to white men (4.1% vs
      9.9%, age adjusted OR 0.45, 95% CI 0.40, 0.51), a difference that persisted with
      only small abatement after controlling for age, income, insurance coverage,
      comorbidity, education and other factors (adjusted OR 0.49, 95% CI 0.43, 0.56)).
      Of men with benign prostatic hyperplasia surgical intervention for that condition
      (133 patients) was more prevalent in black vs white men (12.9% vs 9.1%, adjusted
      OR 1.65, 95% CI 1.10, 2.48). CONCLUSIONS: After controlling for economic factors
      associated with benign prostatic hyperplasia black men were significantly less
      likely to report a prior benign prostatic hyperplasia diagnosis. In contrast,
      surgical intervention typically reserved for severe benign prostatic hyperplasia
      was more common in black men. Our results suggest that race and socioeconomic
      status are independently associated with benign prostatic hyperplasia.

PMID- 18804232
TI  - Office dilation of the female urethra: a quality of care problem in the field of
      urology.
AB  - PURPOSE: Historically dilation of the female urethra was thought to be of value
      in the treatment of a variety of lower urinary tract symptoms. Subsequent work
      has more accurately classified these complaints as parts of various diseases or
      syndromes in which scant data exist to support the use of dilation. Yet Medicare
      reimbursement for urethral dilation remains generous and we describe practice
      patterns regarding female urethral dilation to characterize a potential quality
      of care issue. MATERIALS AND METHODS: Health care use by females treated with
      urethral dilation was compiled using a complementary set of databases. Data sets
      were examined for relevant inpatient, outpatient and emergency room services for
      women of all ages. RESULTS: Female urethral dilation is common (929 per 100,000
      patients) and is performed almost as much as treatment for male urethral
      stricture disease. Approximately 12% of these patients are subjected to costly
      studies such as retrograde urethrography. The overall national costs for
      treatment exceed $61 million per year and have increased 10% to 17% a year since
      1994. A diagnosis of female urethral stricture increases health care expenditures
      by more than $1,800 per individual per year in insured populations. CONCLUSIONS:
      Urethral dilation is still common despite the fact that true female urethral
      stricture is an uncommon entity. This scenario is likely secondary to the
      persistence of the mostly discarded practice of dilating the unstrictured female
      urethra for a wide variety of complaints despite the lack of data suggesting that
      it improves lower urinary tract symptoms.

PMID- 18804233
TI  - Nephron sparing surgery is a feasible and efficient treatment of T1a renal cell
      carcinoma in kidney transplant: a prospective series from a single center.
AB  - PURPOSE: Renal cell carcinoma in a renal graft is a rare condition whose
      incidence will increase in the future. To our knowledge no standardized treatment
      has been established for this disease. We performed a prospective study of
      nephron sparing surgery for small renal cell carcinoma in renal grafts. MATERIALS
      AND METHODS: From January 2002 to December 2006, 2,050 renal graft recipients
      were followed at our transplantation center. Of these patients 7 were diagnosed
      with histologically confirmed renal cell carcinoma in the renal graft, 5 of whom
      presented with T1a renal cell carcinoma and prospectively underwent nephron
      sparing surgery. RESULTS: Five patients with 15 to 30 mm (median 20) renal cell
      carcinoma were included in the study and were treated with nephron sparing
      surgery. Median operative time was 110 minutes (range 60 to 150). Blood loss was
      less than 200 ml in each case. All tumors were pT1aN0M0 with negative margins. No
      postoperative complications were observed (hemorrhage, urinary fistulas, renal
      failure). Preoperative immunosuppressive treatment was not modified
      postoperatively. At 3 months after nephron sparing surgery and at a mean of 17.4
      months of followup (range 5 to 54) no significant impairment of renal function or
      recurrence was observed. CONCLUSIONS: Nephron sparing surgery is a safe and
      efficient procedure for the treatment of renal cell carcinoma in renal grafts,
      resulting in the preservation of renal function and in short-term cancer control.

PMID- 18804234
TI  - Testicular pain following laparoscopic renal surgery.
AB  - PURPOSE: We have observed that a significant number of patients experience
      testicular pain following laparoscopic renal surgery. Since January 2006 all men
      scheduled for laparoscopic renal or adrenal surgery were followed prospectively
      to determine the incidence and characteristics of this pain. MATERIALS AND
      METHODS: All patients had a history and physical examination before surgery,
      during postoperative hospitalization and 4 weeks after surgery. Pain and
      tenderness were scored on a standard 10 point scale. Preoperative and
      postoperative data were collected prospectively. RESULTS: A total of 64 male
      patients (68 sides) met the criteria for evaluation. Ipsilateral testicular pain
      developed in 14 patients (21%). All patients describing pain underwent donor or
      radical nephrectomy. Of the 20 patients who underwent donor nephrectomy 11 (55%)
      experienced pain and of the 15 treated with radical nephrectomy 3 (20%)
      experienced pain. The gonadal vein was preserved in 29 patients and of those
      patients 1 had testicular pain (3.4%). When the gonadal vein was ligated 13 of 39
      patients (33%) experienced pain (OR 14, 95% CI 1.7-115, p = 0.003). Mean pain
      intensity was 4 (range 1 to 8) and improved in all patients. Pain ceased without
      any intervention at a median of 34 days after surgery (range 7 to 110). There
      were no differences in operative time or blood loss between patients with or
      without testicular pain. CONCLUSIONS: Ipsilateral testicular pain can occur after
      laparoscopic renal surgery. The incidence is approximately 50% after donor
      nephrectomy but pain can also occur after radical nephrectomy. Preservation of
      the gonadal vein may be protective. We now warn all male patients scheduled for
      laparoscopic nephrectomy of the possibility of postoperative testicular pain.

PMID- 18804235
TI  - Deficits in urological knowledge among medical students and primary care
      providers: potential for impact on urological care.
AB  - PURPOSE: Recent data indicate a decline in the urological education of third and
      fourth year medical students. To determine if this decline has an impact on the
      treatment of patients we performed a survey to evaluate the general level of
      knowledge, attitudes and practices with regard to common urological issues seen
      in a general medical practice among medical students and faculty involved in
      primary care at an academic institution. MATERIALS AND METHODS: A confidential
      questionnaire was distributed to attendings, residents and fellows, and the
      clinical medical students at our academic institution to ascertain how they
      evaluate and treat patients with common urological complaints. All responses were
      entered into SPSS statistical software. RESULTS: A total of 300 surveys were
      distributed, 150 of which were returned with complete information for data
      analysis. Knowledge with regard to various conditions including hematuria,
      recognition of an age specific abnormality in serum prostate specific antigen and
      overactive bladder was low for all groups. Furthermore, respondents demonstrated
      a low likelihood of requesting formal urological evaluation for these conditions.
      Exposure to a urology elective in medical school had a positive impact on some
      areas of urological evaluation. CONCLUSIONS: General urological knowledge with
      regard to the primary care setting is insufficient. The potential for impact on
      patient care is enormous. These data highlight the need for a definitive
      urological curriculum in medical school as well as continued education at the
      resident and faculty level with regard to evaluation, management and recognition
      of when to request formal urological evaluation in the primary care setting.

PMID- 18804236
TI  - Predicting differential renal function using computerized tomography measurements
      of renal parenchymal area.
AB  - PURPOSE: We evaluated any correlation between measured renal parenchymal area on
      computerized tomography and differential function on (99m)technetium
      mercaptoacetyltriglycine renal scan to ascertain whether computerized tomography
      measurements could predict differential renal function. MATERIALS AND METHODS:
      Between 2005 and 2007 we identified 111 patients who underwent computerized
      tomography and renal scan. Average renal parenchymal thickness was calculated by
      measurements made at the upper and lower poles of each kidney. The product of
      average renal parenchymal thickness and renal length was calculated bilaterally
      and the ratio of parenchymal area was compared to the differential shown on renal
      scan. RESULTS: The average difference between predicted and observed renal
      function was 4.73% (Pearson's correlation coefficient 0.959). Patients with
      positive urine cultures at renal scan were compared to the other 89. The average
      functional difference was 6.54% vs 4.28% (Pearson's correlation 0.955 vs 0.965, p
      = 0.0045). The 89 uninfected patients were then compared based on contrast vs
      noncontrast computerized tomography and obstructed vs unobstructed renal units.
      No statistical difference was found with contrast administration. When compared
      based on evidence of obstruction, unobstructed kidneys resulted in a lower
      Pearson correlation (0.743 vs 0.975) but they had a statistically significant
      average functional difference in favor of unobstructed units (3.28% vs 5.10%, p =
      0.0036). No difference was found in the obstructed group with prior drain
      placement. CONCLUSIONS: Differential renal parenchymal area measured by
      computerized tomography strongly correlates with differential function on renal
      scintigraphy and it may obviate the need for nuclear renal scan in some
      circumstances.

PMID- 18804239
TI  - Normal preoperative urodynamic testing does not predict voiding dysfunction after
      Burch colposuspension versus pubovaginal sling.
AB  - PURPOSE: Urodynamic studies have been proposed as a means of identifying patients
      at risk for voiding dysfunction after surgery for stress urinary incontinence. We
      determined if preoperative urodynamic findings predict postoperative voiding
      dysfunction after pubovaginal sling or Burch colposuspension. MATERIALS AND
      METHODS: Data were analyzed from preoperative, standardized urodynamic studies
      performed on participants in the Stress Incontinence Treatment Efficacy Trial, in
      which women with stress urinary incontinence were randomized to undergo
      pubovaginal sling surgery or Burch colposuspension. Voiding dysfunction was
      defined as use of any bladder catheter after 6 weeks, or reoperation for takedown
      of a pubovaginal sling or Burch colposuspension. Urodynamic study parameters
      examined were post-void residual urine, maximum flow during noninvasive
      flowmetry, maximum flow during pressure flow study, change in vesical pressure at
      maximum flow during pressure flow study, change in abdominal pressure at maximum
      flow during pressure flow study and change in detrusor pressure at maximum flow
      during pressure flow study. The study excluded women with a preoperative post
      void residual urine volume of more than 150 ml or a maximum flow during
      noninvasive flowmetry of less than 12 ml per second unless advanced pelvic
      prolapse was also present. RESULTS: Of the 655 women in whom data were analyzed
      voiding dysfunction developed in 57 including 8 in the Burch colposuspension and
      49 in the pubovaginal sling groups. There were 9 patients who could not be
      categorized and, thus, were excluded from the remainder of the analysis (646). A
      total of 38 women used a catheter beyond week 6, 3 had a surgical takedown and 16
      had both. All 19 women who had surgical takedown were in the pubovaginal sling
      group. The statistical analysis of urodynamic predictors is based on subsets of
      the entire cohort, including 579 women with preoperative uroflowmetry, 378 with
      change in vesical pressure, and 377 with change in abdominal and detrusor
      pressure values. No preoperative urodynamic study findings were associated with
      an increased risk of voiding dysfunction in any group. Mean maximum flow during
      noninvasive flowmetry values were similar among women with voiding dysfunction
      compared to those without voiding dysfunction in the entire group (23.4 vs 25.7
      ml per second, p = 0.16), in the Burch colposuspension group (25.8 vs 25.7 ml per
      second, p = 0.98) and in the pubovaginal sling group (23.1 vs 25.7 ml per second,
      p = 0.17). Voiding pressures and degree of abdominal straining were not
      associated with postoperative voiding dysfunction. CONCLUSIONS: In this carefully
      selected group preoperative urodynamic studies did not predict postoperative
      voiding dysfunction or the risk of surgical revision in the pubovaginal sling
      group. Our findings may be limited by the stringent exclusion criteria and
      studying a group believed to be at greater risk for voiding dysfunction could
      alter these findings. Additional analysis using subjective measures to define
      voiding dysfunction is warranted to further determine the ability of urodynamic
      studies to stratify the risk of postoperative voiding dysfunction, which appears
      to be limited in the current study.

PMID- 18804240
TI  - Differences in the clinical presentation of interstitial cystitis/painful bladder
      syndrome in patients with or without sexual abuse history.
AB  - PURPOSE: We tested the hypothesis that female patients with interstitial
      cystitis/painful bladder syndrome with or without a history of prior sexual abuse
      have different clinical presentations. MATERIALS AND METHODS: Consecutive newly
      diagnosed women with interstitial cystitis/painful bladder syndrome were
      stratified into those with and those without a history of sexual abuse, and
      cohorts were compared. Analysis included demographics, frequency, nocturia,
      voided volumes, pelvic pain urgency frequency, interstitial cystitis symptom
      index and problem index scores, female sexual function index scores and physical
      examination findings. RESULTS: There were 119 subjects, 30 (25%) with a history
      of sexual abuse. Comparing subjects with or without a history of sexual abuse,
      mean daytime frequency (minutes between voids) was 106 vs 60 (p <0.0001),
      nocturic episodes was 1.4 vs 3.1 (p = 0.0002) and voided volume was 234 vs 115 cc
      (p <0.001), respectively. On examination tenderness was more likely elicited on
      suprapubis, vulva, posterior vaginal wall, cervical motion, levators and rectum
      (p <0.05) in subjects with a history of sexual abuse. Female sexual function
      index domain scores were worse for all domains (p <0.05) for subjects with a
      history of sexual abuse. Age, duration of symptoms, pelvic pain urgency
      frequency, interstitial cystitis symptom index, interstitial cystitis problem
      index and hydrodistention volumes were similar. CONCLUSIONS: Female patients with
      interstitial cystitis/painful bladder syndrome with a history of sexual abuse
      have a different clinical presentation compared to those without an abuse
      history. Patients with a history of abuse present with more pain and fewer
      voiding problems. Patients with interstitial cystitis/painful bladder syndrome
      with a sexual abuse history may have increased central sensitization.

PMID- 18804241
TI  - The effects of lifestyle factors on the incidence of nocturia.
AB  - PURPOSE: Cross-sectional studies have shown an association between obesity and
      nocturia but controversial findings on the relationship between smoking, alcohol
      and coffee consumption, and nocturia. Prospective studies of the role of
      lifestyle factors in individuals with nocturia are scarce. We investigated the
      effects of lifestyle factors on the incidence of nocturia. MATERIALS AND METHODS:
      The target population consisted of men who were 50, 60 or 70 years old and
      residing in Tampere in 1994. A questionnaire was mailed to 3,143 randomly
      selected men in 1994 and the survey was repeated in 1999 with the 2,837 who were
      still eligible. The followup sample consisted of 1,580 men with information on
      nocturia at baseline and 5-year followup. Nocturia was assessed by the Danish
      Prostate Symptoms Score 1 questionnaire and graded as mild--1 or 2, moderate--3
      or 4 and severe--5 or more nightly voids. RESULTS: Higher body mass index at
      baseline was associated with an increased incidence of nocturia. Obese men were
      at 1.6 times (95% CI 1.1-2.4) higher risk for mild nocturia and at 2.3 times (95%
      CI 1.1-4.7) higher risk for moderate or severe nocturia compared with men who had
      a normal body mass index. Men who consumed less than 150 gm alcohol per week were
      at lower risk for moderate or severe nocturia than abstainers (adjusted incidence
      rate ratio 0.4, 95% CI 0.2-0.8). No statistically significant associations were
      found for smoking and coffee consumption. The frequency of nocturia at baseline
      did not increase the incidence of obesity at followup. CONCLUSIONS: Our findings
      suggest that obesity increases the risk of nocturia. The link between other
      lifestyle factors and nocturia is weak or absent.

PMID- 18804242
TI  - Genitofemoral nerve injury after laparoscopic varicocelectomy in adolescents.
AB  - PURPOSE: Genitofemoral nerve injury is an underappreciated complication after
      laparoscopic varicocele ligation in teenage boys. We describe the incidence
      according to ligation instrument and the pattern of spontaneous symptom
      resolution. MATERIALS AND METHODS: Patients who underwent laparoscopic varicocele
      ligation between 2004 and 2007 were retrospectively grouped by ligation modality
      (clipping or cautery by ultrasonic shears). The incidence of iatrogenic
      genitofemoral nerve injury was assessed and compared. To illustrate the pattern
      of resolution, 1 affected patient documented the decreasing area of paresthesia
      through time on a topographic map. RESULTS: During the study period laparoscopic
      varicocele ligation was performed using ultrasonic shears in 12 boys and
      endoscopic clips/cold dissection in 15. Genitofemoral nerve injury occurred in 2
      patients using ultrasonic shears (17%) and no patient in the clip/cold dissection
      group (p = 0.10). In both patients the paresthesias resolved completely by 8
      months. CONCLUSIONS: Genitofemoral nerve injury may be more frequent when the
      dissection is performed using "hot" methods such as cautery by ultrasonic shears.
      Preoperatively, patients should be made aware of the relatively high incidence
      and the usually self-limiting nature of this complication.

PMID- 18804245
TI  - Investigating the associations between nocturia and sleep disorders in
      perimenopausal women.
AB  - PURPOSE: We determined the associations between nocturia and sleep disorders in
      perimenopausal women. MATERIALS AND METHODS: A total of 100 women with nocturia
      were compared to 200 without nocturia. Obstructive sleep apnea, insomnia, anxiety
      and menopausal stage were assessed using validated questionnaires. Comorbidities
      associated with nocturia were determined by bivariate analysis and multivariate
      logistic regression. RESULTS: Independent associations for nocturia were anxiety
      (OR 2.11, 95% CI 1.08-4.13), black American race (OR 2.00, 95% CI 1.06-3.85),
      obstructive sleep apnea symptoms (OR 1.73, 95% CI 1.18-2.53) and insomnia (OR
      1.11, 95% CI 1.05-1.12). CONCLUSIONS: Nocturia is associated with sleep disorders
      in perimenopausal women.

PMID- 18804246
TI  - Serosa lined and tapered ileum as primary and secondary continence mechanism for
      various catheterizable pouches.
AB  - PURPOSE: Incontinence of catheterizable ileocecal pouches with an umbilical stoma
      using the original Mainz pouch technique can be repaired by a secondary ileal
      intussusception nipple fixed in the ileocecal valve. In cases of a modified Mainz
      pouch with ureteral anastomosis to the prevalvular ileal segment another form of
      troubleshooting is necessary. MATERIALS AND METHODS: In 4 of 112 patients (3.6%)
      with the modified Mainz pouch described by Roth incontinence or stenosis of the
      catheterizable stoma occurred. A 24 to 30 cm segment of ileum was isolated. The
      proximal 8 to 10 cm were tapered and seroserosally embedded in the U-shaped 2 x 8
      to 10 cm long remainder of the segment. After excising the insufficient efferent
      limb this ileal segment was anastomosed to the pouch and the umbilicus with
      tapered ileum acting as the continence mechanism. In a fifth patient such a
      segment was used for ileocystoplasty with an umbilical stoma after bladder neck
      closure. RESULTS: At a median followup of 6 months (range 5 to 64) all 5 patients
      were fully continent with regular, easy self-catheterization via the umbilicus.
      CONCLUSIONS: The introduced method seems to be a promising continence mechanism
      for various forms of catheterizable pouches, not only for troubleshooting.

PMID- 18804249
TI  - High levator myorrhaphy for transvaginal suspension of the vaginal apex: long
      term results.
AB  - PURPOSE: We evaluated the long-term outcome and complications of high levator
      myorrhaphy for vaginal apical defects. MATERIALS AND METHODS: A total of 286
      patients underwent high levator myorrhaphy. Patients underwent preoperative and
      postoperative urogynecologic assessment, including evaluation of prolapse stage
      according to the international pelvic organ prolapse staging system and
      conventional urodynamic testing. Quality of life was evaluated using the prolapse
      quality of life questionnaire. We considered failure as vaginal prolapse stage 2
      or greater according to the pelvic organ prolapse staging system. RESULTS: A
      total of 272 patients with a mean age of 60.4 years were available for analysis.
      Mean followup was 5 years. In 247 patients we associated tension-free cystocele
      repair with Marlex mesh. In 50.7% of patients high levator myorrhaphy was done
      with curative intent, while in the remaining 49.3% it was a preventive measure.
      Complications included a rectal tear in 2 cases, Marlex mesh erosion in 23
      (8.4%), vaginal vault abscess in 1, pararectal hematoma in 2 and buttock pain in
      2. Anatomical evaluation at followup revealed a 96.7% cure rate for apical
      defects and a 26.8% incidence of cystocele. We observed improvement in filling,
      voiding and post-void symptoms. Quality of life evaluation showed improvement in
      all domains. We detected a 9.6% incidence of de novo dyspareunia. CONCLUSIONS:
      High levator myorrhaphy is a safe and effective procedure for preventing and
      curing vaginal apical defects. The simplicity of this surgical procedure, its
      short learning curve, the lack of severe complications and its low costs combined
      with symptomatic relief and improvement in quality of life encourage its use for
      the cure and routine prevention of vaginal apical prolapse.

PMID- 18804250
TI  - Individual and social environment influences on smoking in children and
      adolescents.
AB  - OBJECTIVES: A precise knowledge of the risk factors for childhood and adolescent
      smoking is crucial for the development of appropriate preventive measures. This
      study investigated current smoking prevalence and the social and regional
      correlates for smoking among minors (children and adolescents aged 12-17 years)
      in Germany. METHODS: Bivariate data analysis was performed on the basis of a
      representative national cross-sectional study performed in 2004, and
      multivariable logistic regression models were calculated separately for boys and
      girls. All correlates identified as significant in the bivariate model were used
      in the multivariable analysis. STUDY DESIGN: The database used in this research
      was from the study 'Drug Affinity of Young People in the Federal Republic of
      Germany 2004', with approximately 1298 children and adolescents aged 12-17 years.
      RESULTS: Twelve percent of male and 9% of female adolescents in Germany reported
      that they are habitual smokers, and 12% of male and 13% of female adolescents
      reported that they are occasional smokers. Multivariable data analysis shows that
      living in a large city is protective for adolescents in terms of local
      disparities. The educational level of the respondents also correlates
      significantly with smoking behaviour. The percentage of adolescent smokers is
      lowest among those with a high level of education. The presence of smokers in the
      household is associated with a significantly higher prevalence of smoking among
      adolescents compared with those growing up in a non-smoking household.
      CONCLUSION: Smoking is a major public health problem among German children and
      adolescents. Control measures must tackle the structural and social pressures
      that shape smoking behaviour during childhood.

PMID- 18804251
TI  - Viraemia and HIV-1 drug resistance mutations among patients receiving
      antiretroviral treatment in Mozambique.
AB  - This study was conducted among individuals taking first-line antiretroviral
      treatment (ART) for at least 12 months under programme conditions in Maputo,
      Mozambique in order to report on the level of detectable viraemia and the
      proportion and types of drug resistance mutations among those with detectable
      viral loads. HIV-1 RNA viral load levels (lower detection limit <50 copies/ml)
      were measured, and resistance mutations were sequenced. One hundred and forty
      nine consecutive patients (69% females, median age 36 years) were included after
      a mean follow-up time of 23 months. One hundred and seven (72%; 95% CI 64-79) had
      undetectable viral load, while in 42 (28%, 95% CI 21-36) viral load was
      detectable (range 50-58884 copies/ml). From 15 patients with viral load >1000
      copies/ml, 12 viruses were sequenced: eight were C subtypes and four were
      circulating recombinant forms (CRF08). Eight (5%; 95% CI 2-9) patients with
      detectable viral load had one or more major resistance mutations. Nucleoside
      reverse transcriptase inhibitor (NRTI) and non-NRTI mutations were observed.
      There were no major mutations for resistance to protease inhibitors. In Maputo,
      the level of detectable viraemia is reassuringly low. While embarking on ART
      scale-up, wider surveillance is warranted to monitor programme quality and limit
      the development of drug resistance, which remains a major potential challenge for
      the future of ART in Africa.

PMID- 18804252
TI  - Diet as a factor in unexpectedly low prevalence of Helicobacter pylori infection.

PMID- 18804253
TI  - Macropinocytosis and cytoskeleton contribute to dendritic cell-mediated HIV-1
      transmission to CD4+ T cells.
AB  - Dendritic cells (DCs) are among the first immune cells to encounter HIV-1 at the
      initial infection. DCs efficiently transfer HIV-1 to CD4+ T cells via infectious
      or virological synapses formed between DCs and T cells. Retroviruses exploit the
      cytoskeletal network to facilitate viral infection and dissemination; however,
      the role of the cytoskeleton in DC-mediated HIV-1 transmission is unknown. Here,
      we report that intact cytoskeleton is essential for DC-mediated HIV-1
      transmission to CD4+ T cells. We found that macropinocytosis of HIV-1 contributes
      to DC-mediated HIV-1 endocytosis and transmission. Blocking HIV-1
      macropinocytosis and disrupting actin or microtubules in DCs with specific
      inhibitors significantly prevented DC-mediated HIV-1 trans-infection of CD4+ T
      cells. Altered HIV-1 trafficking and impaired formation of virological synapses
      primarily accounted for the inhibition of viral transmission by cytoskeletal
      inhibitors. Our results provide new insights into the mechanisms underlying DC
      mediated HIV-1 transmission to CD4+ T cells via the cytoskeletal network.

PMID- 18804255
TI  - Multi-criteria evaluation of wastewater treatment plant control strategies under
      uncertainty.
AB  - The evaluation of activated sludge control strategies in wastewater treatment
      plants (WWTP) via mathematical modelling is a complex activity because several
      objectives; e.g. economic, environmental, technical and legal; must be taken into
      account at the same time, i.e. the evaluation of the alternatives is a multi
      criteria problem. Activated sludge models are not well characterized and some of
      the parameters can present uncertainty, e.g. the influent fractions arriving to
      the facility and the effect of either temperature or toxic compounds on the
      kinetic parameters, having a strong influence in the model predictions used
      during the evaluation of the alternatives and affecting the resulting rank of
      preferences. Using a simplified version of the IWA Benchmark Simulation Model No.
      2 as a case study, this article shows the variations in the decision making when
      the uncertainty in activated sludge model (ASM) parameters is either included or
      not during the evaluation of WWTP control strategies. This paper comprises two
      main sections. Firstly, there is the evaluation of six WWTP control strategies
      using multi-criteria decision analysis setting the ASM parameters at their
      default value. In the following section, the uncertainty is introduced, i.e.
      input uncertainty, which is characterized by probability distribution functions
      based on the available process knowledge. Next, Monte Carlo simulations are run
      to propagate input through the model and affect the different outcomes. Thus (i)
      the variation in the overall degree of satisfaction of the control objectives for
      the generated WWTP control strategies is quantified, (ii) the contributions of
      environmental, legal, technical and economic objectives to the existing variance
      are identified and finally (iii) the influence of the relative importance of the
      control objectives during the selection of alternatives is analyzed. The results
      show that the control strategies with an external carbon source reduce the output
      uncertainty in the criteria used to quantify the degree of satisfaction of
      environmental, technical and legal objectives, but increasing the economical
      costs and their variability as a trade-off. Also, it is shown how a preliminary
      selected alternative with cascade ammonium controller becomes less desirable when
      input uncertainty is included, having simpler alternatives more chance of
      success.

PMID- 18804254
TI  - Soluble CD4 broadens neutralization of V3-directed monoclonal antibodies and
      guinea pig vaccine sera against HIV-1 subtype B and C reference viruses.
AB  - To better understand the limits of antigenic reactivity and epitope accessibility
      of the V3 domain of primary HIV-1 isolates, we evaluated three human anti-V3
      monoclonal antibodies (mAbs) and selected guinea pig vaccine sera for
      neutralization against reference panels of subtype B and C pseudoviruses derived
      from early stage infections. The mAbs and vaccine sera potently neutralized
      several prototype viruses, but displayed substantially less neutralization of
      most reference strains. In the presence of soluble CD4 (sCD4), the breadth of V3
      mediated neutralization was increased; up to 80% and 77% of the subtype B and C
      viruses respectively were sensitive to V3-mediated neutralization. Unlike sCD4,
      the reaction of CD4-binding site mAbs b12 and F105 with native virus did not lead
      to full exposure of the V3 domain. These findings confirm that V3 antibodies
      recognize most primary viral strains, but that the epitope often has limited
      accessibility in the context of native envelope spike.

PMID- 18804256
TI  - Drivers of water quality in a large water storage reservoir during a period of
      extreme drawdown.
AB  - This study examined the drivers of water quality in a large water storage
      reservoir (Lake Hume) during a period of extreme drawdown (to less than 3% of
      capacity). During the period of extreme drawdown, the reservoir can be thought of
      as consisting of three separate but inter-related parcels of water. The warm
      surface mixed layer was about 6m deep. Cold water inflows from the Mitta Mitta
      River undershot the surface mixed layer in the Mitta Mitta arm of the reservoir
      and flowed along the bottom of the reservoir to the Dam Wall without substantial
      interaction with the surface mixed layer. When inflows from the Murray River
      occurred, the temperature of these inflows was similar to that of the surface
      mixed layer within the dam and the flows appeared to move within the surface
      mixed layer towards the Dam Wall. These Murray River inflows were insufficient to
      promote total mixing of the surface and bottom waters. The Murray River arm of
      the reservoir became a 'hot spot' for nutrient production. Stratification and
      subsequent anoxic conditions promoted the release of nutrients - ammonium,
      organic N and total P - from the sediments into the overlying hypolimnion.
      Because the depth of the lake was relatively shallow due to the extreme drawdown,
      wind driven events lead to a substantial deepening (turnover) of the thermocline
      allowing periodic pulses of nutrients into the warm surface layer. These nutrient
      pulses appeared to stimulate cyanobacterial growth. Warm inflows from the Murray
      River then served to push the blooms formed in the Murray arm into the main body
      of the lake.

PMID- 18804257
TI  - Coagulation dynamics of fractal flocs induced by enmeshment and electrostatic
      patch mechanisms.
AB  - The size and structure of flocs during floc formation were monitored for various
      coagulation mechanisms. Two distinctive mechanisms, namely, enmeshment and
      electrostatic patch, govern the dynamics of kaolin particles coagulation by
      polyaluminum chloride (PACl). They were investigated by small angle static light
      scattering (SASLS) and solid-state (27)Al NMR. In addition, a novel wet SEM
      (WSEM) was used in-situ to image the morphology of the aggregate in aqueous
      solution. Synthetic suspended particles were coagulated by two PACl products, a
      commercial product (PACl) and one laboratory product (PACl-E). The PACl-E
      contained more than 60% Al(13) while the PACl contained only 7% Al(13), with
      large percentage of colloidal Al. For coagulation by PACl at neutral pH and high
      dosage where the strong repulsion between particles occurs, the enmeshment ruled
      by reaction-limited aggregation (RLA) results in larger sweep flocs as well as
      higher fractal dimensional structure. For coagulation by PACl-E at alkaline pH
      and low dosage, the flocs were coagulated predominately by electrostatic patch
      with Al(13) aggregates. At such condition, it is likely that diffusion-limited
      aggregation (DLA) predominately rule PACl-E coagulation. The fractal dimension
      (D(s)) values of PACl and PACl-E flocs formed at enmeshment and electrostatic
      patch increased with dosage, respectively. When breakage of flocs occurs, the
      breakage rate of PACl-E flocs is slower than that of sweep flocs. By WSEM
      imaging, the adsorption of spherical Al precipitates onto the particles was
      observed to form sweep flocs with a rough and ragged contour, while the PACl-E
      flocs were formed with a smooth and glossy structure.

PMID- 18804258
TI  - Urinary 1-hydroxypyrene, air pollution exposure and associated life style factors
      in pregnant women.
AB  - 1-hydroxypyrene (1-OHP) is a biomarker of exposure to polycyclic aromatic
      hydrocarbons (PAHs). PAHs are pollutants produced by the combustion of organic
      material, and could be found both indoors and outdoors. Prenatal exposure to
      these compounds has been associated with retarded intrauterine growth and
      respiratory problems in children. The objective of this study is to describe the
      1-OHP levels in urine in pregnant women in the INMA cohort in Valencia, and to
      study the association with socio-demographic and lifestyle variables, as well as
      with indicators of air pollution. The study population is a sub-sample (n: 204)
      of a cohort of pregnant women in the multicentre INMA project in Valencia
      (Spain). Urine samples were taken in week 12 of gestation, and 1-OHP was
      analyzed, and adjusted for creatinine. Socio-demographic and lifestyle
      information was collected using a questionnaire. Data from the monitoring
      stations in Valencia were used to assign levels of exposure to nitrogen dioxide
      (NO2), sulphur dioxide (SO2), total suspended particulates (TSP) and carbon
      monoxide (CO). The median 1-OHP level was 0.061 muicrool/mol of creatinine. Women
      who smoked had higher 1-OHP levels (0.095 micromol/mol of creatinine) than non
      smokers (0.050 micromol/mol of creatinine). The variables predicting 1-OHP levels
      on linear multivariate analysis were: tobacco consumption, consumption of fried
      and smoked foods. There was also a significant association with NO2 levels 4 and
      5 days before the samples were taken. The 1-OHP levels found in pregnant women in
      Valencia were higher than those found among women in reports in USA. 1
      hydroxypyrene could be a good marker of exposure to PAHs from tobacco and diet,
      and also a useful marker of short term exposure to air pollution.

PMID- 18804259
TI  - Influence of liming on metal sequestration in lake sediments over recent decades.
AB  - Sediment profiles from five limed and six reference softwater lakes included in
      Swedish monitoring programmes were subjected to multi-element analysis to
      investigate the influence of lime treatment since 1977 on the sequestration of
      metals in lake sediments. We hypothesised that liming causes increased
      sedimentation of elements for which the mobility is primarily controlled by pH,
      e.g. Al, Cd, Co, Ni and Zn, whereas elements that are less influenced by pH
      fluctuations, e.g. Hg and Pb, are not affected by lime treatment. Further, we
      introduce a normalisation of metal concentrations with respect to Cu
      concentration in order to separate the effects of lime treatment from those
      related to temporal trends in airborne metal deposition or short-term variations
      in environmental conditions. This approach is shown to emphasise the effect of
      liming on the sediment accumulation of metals, thus separating it from other
      sources of variability. We found that liming causes increased sequestration of
      Al, As, Cd, Co, Fe, Mn, Ni and Zn, in the case of As and Co probably at least
      partly caused by an increased adsorption to Al, Fe and Mn oxyhydroxides. On the
      other hand, no influence of lime treatment could be demonstrated for Hg, Pb, Cr,
      V and P, despite an increase of pH by about two units.

PMID- 18804260
TI  - Assessing the effects of the Prestige oil spill on the European shag
      (Phalacrocorax aristotelis): trace elements and stable isotopes.
AB  - The Prestige oil spill resulted in the mortality of several seabird species on
      the Atlantic NW coast of Spain. Shag casualties were particularly relevant, since
      populations are resident in the area the whole year round and because of several
      features which make them highly vulnerable to environmental hazards. Ecological
      catastrophes give us the opportunity of collecting samples which, otherwise,
      would be difficult to obtain. We examine the potential of shag corpses as
      bioindicators of inorganic pollution and the possible factors of variability,
      such as biological traits (sex, age) or nutrition status. We determined trace
      elements (Hg, Se, Cr, Pb, Zn and Cu) and isotopic signatures (15N, 13C) in soft
      tissues (muscle, liver) and in primary feathers formed at different times (before
      and after the Prestige) in individuals of known sex and age, collected at the
      time of the Prestige disaster. These were compared with data from another group
      of shags trapped accidentally in fishing gear in 2005. Our results did not seem
      to be affected by sex or age on any of the analysed variables. The higher
      nitrogen isotopic signatures in the soft tissues of the Prestige shags may be
      related to the nutrition stress caused by a poorer body condition, which is also
      reflected in increasing levels of some metals in the liver. This isotopic
      enrichment was also observed in newly forming feathers when compared to the old
      ones. On the other hand, the lower delta15N and Hg values in shag feathers from
      2005 point to a shift in feeding resources to prey of lower trophic levels. We
      found that feather features (being an inert tissue and having a conservative
      composition), if combined with careful dating and chemical analysis, offer a very
      useful tool to evaluate temporal and spatial changes in seabird ecology in
      relation to pollution events.

PMID- 18804261
TI  - SPME-GCMS study of the natural attenuation of aviation diesel spilled on the
      perennial ice cover of Lake Fryxell, Antarctica.
AB  - In January 2003, a helicopter crashed on the 5 m thick perennial ice cover of
      Lake Fryxell (McMurdo Dry Valleys, East Antarctica), spilling approximately 730 l
      of aviation diesel fuel (JP5-AN8 mixture). The molecular composition of the
      initial fuel was analyzed by solid phase microextraction (SPME) gas
      chromatography-mass spectrometry (GC-MS), then compared to the composition of the
      contaminated ice, water, and sediments collected a year after the spill.
      Evaporation is the major agent of diesel weathering in meltpool waters and in the
      ice. This process is facilitated by the light non-aqueous phase liquid properties
      of the aviation diesel and by the net upward movement of the ice as a result of
      ablation. In contrast, in sediment-bearing ice, biodegradation by both alkane-
      and aromatic-degraders was the prominent attenuation mechanism. The composition
      of the diesel contaminant in the ice was also affected by the differential
      solubility of its constituents, some ice containing water-washed diesel and some
      ice containing exclusively relatively soluble low molecular weight aromatic
      hydrocarbons such as alkylbenzene and naphthalene homologues. The extent of
      evaporation, water washing and biodegradation between sites and at different
      depths in the ice are evaluated on the basis of molecular ratios and the results
      of JP5-AN8 diesel evaporation experiment at 4 degrees C. Immediate spread of the
      aviation diesel was enhanced where the presence of aeolian sediments induced
      formations of meltpools. However, in absence of melt pools, slow spreading of the
      diesel is possible through the porous ice and the ice cover aquifer.

PMID- 18804262
TI  - The Kaiser Permanente Colorado Clinical Pharmacy Anticoagulation Service as a
      model of modern anticoagulant care.
AB  - The Clinical Pharmacy Anticoagulation Service (CPAS) at Kaiser Permanente
      Colorado grew from a single pharmacist assisting a single physician to a
      comprehensive service staffed by over 20 employees. CPAS provides care for over
      7200 patients with each CPAS pharmacist managing all aspects of anticoagulation
      therapy for 150 to 500 patients. Unique aspects of CPAS include its centralized
      organization structure, the use of telepharmacy, collaboration drug therapy
      management agreement with referring physicians and a robust research agenda.
      Results of various CPAS research projects have been published in the peer
      reviewed medical literature.

PMID- 18804263
TI  - Pediatric robotic-assisted laparoscopic augmentation ileocystoplasty and
      Mitrofanoff appendicovesicostomy: complete intracorporeal--initial case report.
AB  - INTRODUCTION: To the best of our knowledge, we report the first case of complete
      intracorporeal robotic-assisted laparoscopic augmentation ileocystoplasty and
      Mitrofanoff appendicovesicostomy in a pediatric patient, outlining the surgical
      technique and short-term results. TECHNICAL CONSIDERATIONS: The operative steps
      of the open procedure were replicated laparoscopically using robotic-assistance.
      In brief, 5 transperitoneal laparoscopic ports were placed before docking the da
      Vinci S robotic system. A 20-cm ileal segment was isolated, and the
      gastrointestinal anastomosis was performed in an end-to-end fashion using
      intracorporeal suturing. The appendix was anastomosed to the right posterior wall
      of the bladder over an 8F feeding tube in an extravesical fashion. The bladder
      was incised in a coronal plane, and the simple ileal on-lay patch was anastomosed
      to the posterior and anterior walls of the bladder. A suprapubic catheter and
      pelvic drain were placed, and the Mitrofanoff stoma was then fashioned.
      Cystography was performed at 4 weeks postoperatively. CONCLUSIONS: This
      preliminary first successful report suggests that robotic-assisted
      ileocystoplasty and appendicovesicostomy is feasible. A reasonable outcome with
      early recovery, resumption of normal activities, and excellent cosmesis can be
      achieved in selected patients. However, whether a robotic-assisted approach
      provides any significant advantages over conventional open procedures is yet to
      be determined with a large case series.

PMID- 18804264
TI  - Spiral sling salvage anti-incontinence surgery for women with refractory stress
      urinary incontinence: surgical outcome and satisfaction determined by patient
      driven questionnaires.
AB  - PURPOSE: Female patients with refractory stress urinary incontinence (SUI) are a
      unique surgical challenge. They undergo multiple surgical procedures and
      eventually are left with urethral closure and continent diversion as their final
      option. We previously presented our initial experience of a technique that
      provides circumferential coaptation of the urethra in patients with severe
      urethral incompetence due to neurologic injuries or congenital anomalies. This
      study expands on that experience and reports on the clinical and quality of life
      of patients after spiral sling placement in a defined population of patients with
      refractory SUI. METHODS: We prospectively evaluated 46 patients with refractory
      SUI who had undergone spiral sling placement. The surgical outcome was determined
      by clinical history and physical examination and, primarily, by patient self
      assessment and included validated symptom, bother, and quality-of-life
      questionnaires. RESULTS: Their mean age was 62 years. The mean follow-up was 15
      months. At presentation, the patients had undergone a mean of 2.8 incontinence
      procedures and wore a mean of 5.5 pads daily. The mean pad use decreased to 1.3
      pads daily (P <.05). Preoperatively, the mean severity and bother score from the
      SUI symptoms was 3.0 and 2.9, respectively (0, none; 3, severe). Postoperatively,
      these numbers decreased to 1.0 and 0.8 (P <.05). The mean overall improvement in
      symptoms was 82%. No perioperative complications developed. The procedure failed
      in 1 patient, who underwent urethral closure with urinary diversion. Two patients
      underwent repeat proximal spiral sling procedure. CONCLUSIONS: The spiral sling
      is an effective salvage transvaginal procedure that can be considered for female
      patients with refractory SUI.

PMID- 18804265
TI  - Point: effect of radiation-associated second malignancies on prostate cancer
      survival.

PMID- 18804266
TI  - Update on sentinel lymph node biopsy in gynecologic cancers.
AB  - The sentinel lymph node biopsy (SLNB) holds the promise of more accurate staging
      of the primary tumor and fewer wound complications and lymphedema than associated
      with lymphadenectomy. Regional lymphadenectomy may no longer be a requirement in
      SLNB-negative patients if the SLN procedure is adequately validated in
      prospective clinical trials for gynecologic malignancies.

PMID- 18804267
TI  - Sparing fertility in young patients with endometrial cancer.
AB  - The objective of this review is to recognize the characteristics of endometrial
      adenocarcinoma in young patients and to evaluate the published experience with
      conservative approach in patients with endometrial adenocarcinoma. We searched
      MEDLINE articles describing patients with endometrial adenocarcinoma who were
      treated with hormonal therapy. The search included articles published between
      January 1966 and January 2007. Endometrial carcinoma in patients under 45 years
      of age is an unusual condition that shows a more favorable pattern than in older
      patients. One hundred thirty three patients were found in the search. The average
      duration of hormonal therapy was approximately 6 months. The average response
      time was 12 weeks. Seventy six percent of patients treated with hormonal therapy
      had a complete response and the other 24% never responded to treatment. Of those
      who initially responded, 66% didn't show recurrence of disease. The other 34% had
      a relapse. There have been published 4 deaths of patients conservatively managed.
      A conservative approach in these patients can offer reasonable oncological
      security and the opportunity of fulfilling their maternal desires in selected
      cases. However, consideration should be taken regarding the potential adverse
      outcomes that have been recently published in the literature.

PMID- 18804269
TI  - Immunoglobulin therapy: methods of delivery.

PMID- 18804270
TI  - Probiotics for the treatment or prevention of eczema.

PMID- 18804271
TI  - Different types of T-effector cells orchestrate mucosal inflammation in chronic
      sinus disease.
AB  - BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by
      the accumulation of inflammatory cells; however, an eosinophil predominance is
      seen in white (Belgian), but not Asian (south Chinese), patients with polyps.
      OBJECTIVE: We sought to investigate the association of inflammatory cell
      predominance with regulatory T-cell and T-effector cell patterns. METHODS: Nasal
      mucosal tissue was obtained from 26 consecutive Belgian patients with CRSwNP and
      21 Belgian control subjects and 29 south Chinese patients with CRSwNP and 29
      south Chinese control subjects, who all underwent phenotyping, including nasal
      endoscopy and computed tomographic scanning. Tissues were investigated for
      granulocytes and their products and T-effector/regulatory T cells and related
      cytokines. RESULTS: Both CRSwNP groups were comparable in terms of symptoms,
      computed tomographic scan results, and nasal endoscopy results, but asthma
      comorbidity was significantly higher in white patients. Tissue from white
      patients with CRSwNP was characterized by eosinophilic inflammation (eosinophil
      cationic protein/myeloperoxidase ratio > 2), whereas samples from Asian patients
      were biased toward neutrophilic inflammation (eosinophil cationic
      protein/myeloperoxidase ratio = 0.25). Both CRSwNP groups demonstrated
      significant upregulation of the T-cell activation marker soluble IL-2 receptor
      alpha and significant downregulation of Foxp3 expression and TGF-beta1 protein
      content versus their respective control groups. However, whereas white patients
      displayed a significant increase in T(H)2 cytokine and related marker levels
      versus control subjects and versus Asian patients, the latter showed a
      T(H)1/T(H)17 cell pattern versus control tissue. CONCLUSION: Nasal polyps
      (CRSwNP) from white and Asian patients are both characterized by T-cell
      activation and impaired regulatory T-cell function; however, T-effector cells in
      the samples from white patients were T(H)2-biased, whereas samples from their
      Asian counterparts demonstrated a T(H)1/T(H)17 polarization.

PMID- 18804272
TI  - Variability of clinical and laboratory features among patients with ribonuclease
      mitochondrial RNA processing endoribonuclease gene mutations.
AB  - BACKGROUND: Cartilage hair hypoplasia is an autosomal recessive type of
      metaphyseal chondrodysplasia, caused by mutations in the ribonuclease
      mitochondrial RNA processing (RMRP) gene. Typical features of cartilage hair
      hypoplasia include short stature, a predisposition to malignancy, and a variable
      degree of impairment of cellular immunity. OBJECTIVE: We sought to describe the
      heterogeneity of clinical and immunologic phenotype in 12 consecutive patients
      with RMRP mutations who were referred to 2 different institutions for immunologic
      evaluation. METHODS: We have retrospectively analyzed the clinical and laboratory
      features in 12 patients with molecular defects in the RMRP gene. T-cell
      repertoire was investigated by quantitating Vbeta families' expression and
      analyzing their diversity. T-cell receptor excision circle analysis was used to
      study thymic output. RESULTS: All 12 patients had significant immune
      abnormalities, leading to severe immune deficiency in 9. CD8 lymphocytopenia was
      identified as a novel phenotype associated with RMRP mutations. Significant, even
      intrafamilial, phenotypic heterogeneity was observed. In 3 cases, severe
      immunodeficiency was the only phenotypic manifestation associated with RMRP
      mutations, a novel finding. Mutations leading to significant immune defects were
      most often located in the promoter, and the first case of a compound heterozygote
      for 2 such mutations is reported. CONCLUSION: This report broadens the spectrum
      of phenotypes associated with RMRP mutations and suggests that mutations in this
      gene should be considered when evaluating patients with combined immune
      deficiency, regardless of the presence of other manifestations.

PMID- 18804273
TI  - Production of transgenic recloned piglets harboring the human granulocyte
      macrophage colony stimulating factor (hGM-CSF) gene from porcine fetal
      fibroblasts by nuclear transfer.
AB  - We used nuclear transfer (NT) to develop transgenic female pigs harboring goat
      beta-casein promoter/human granulocyte-macrophage colony stimulating factor (hGM
      CSF). The expression of hGM-CSF was specific to the mammary gland, and the
      glycosylation-derived size heterogeneity corresponded to that of the native human
      protein. Although various cell types have been used to generate cloned animals,
      little is currently known about the potential use of fibroblasts derived from a
      cloned fetus as donor cells for nuclear transfer. The developmental potential of
      porcine cloned fetal fibroblasts transfected with hGM-CSF was evaluated in the
      present study. Cloned fetal fibroblasts were isolated from a recipient following
      the transplantation of NT embryos. The cells were transfected with both hGM-CSF
      and the neomycin resistance gene in order to be used as donor cells for NT.
      Reconstructed embryos were implanted into six sows during estrus; two of the
      recipient sows delivered seven healthy female piglets with the hGM-CSF gene
      (confirmed with PCR and fluorescent in situ hybridization) and microsatellite
      analysis confirmed that the clones were genetically identical to the donor cells.
      The expression of hGM-CSF was strong in the mammary glands of a transgenic pig
      that died a few days prior to parturition (110 d after AI). These results
      demonstrated that somatic cells derived from a cloned fetus can be used to
      produce recloned and transgenic pigs.

PMID- 18804274
TI  - Childhood outcomes after prescription of antibiotics to pregnant women with
      preterm rupture of the membranes: 7-year follow-up of the ORACLE I trial.
AB  - BACKGROUND: The ORACLE I trial compared the use of erythromycin and/or
      amoxicillin-clavulanate (co-amoxiclav) with that of placebo for women with
      preterm rupture of the membranes without overt signs of clinical infection, by
      use of a factorial randomised design. The aim of the present study--the ORACLE
      Children Study I--was to determine the long-term effects on children of these
      interventions. METHODS: We assessed children at age 7 years born to the 4148
      women who had completed the ORACLE I trial and who were eligible for follow-up
      with a structured parental questionnaire to assess the child's health status.
      Functional impairment was defined as the presence of any level of functional
      impairment (severe, moderate, or mild) derived from the mark III Multi-Attribute
      Health Status classification system. Educational outcomes were assessed with
      national curriculum test results for children resident in England. FINDINGS:
      Outcome was determined for 3298 (75%) eligible children. There was no difference
      in the proportion of children with any functional impairment after prescription
      of erythromycin, with or without co-amoxiclav, compared with those born to
      mothers who received no erythromycin (594 [38.3%] of 1551 children vs 655 [40.4%]
      of 1620; odds ratio 0.91, 95% CI 0.79-1.05) or after prescription of co
      amoxiclav, with or without erythromycin, compared with those born to mothers who
      received no co-amoxiclav (645 [40.6%] of 1587 vs 604 [38.1%] of 1584; 1.11, 0.96
      1.28). Neither antibiotic had a significant effect on the overall level of
      behavioural difficulties experienced, on specific medical conditions, or on the
      proportions of children achieving each level in reading, writing, or mathematics
      at key stage one. INTERPRETATION: The prescription of antibiotics for women with
      preterm rupture of the membranes seems to have little effect on the health of
      children at 7 years of age. FUNDING: UK Medical Research Council.

PMID- 18804275
TI  - Antibiotics in preterm labour--the ORACLE speaks.

PMID- 18804276
TI  - Childhood outcomes after prescription of antibiotics to pregnant women with
      spontaneous preterm labour: 7-year follow-up of the ORACLE II trial.
AB  - BACKGROUND: The ORACLE II trial compared the use of erythromycin and/or
      amoxicillin-clavulanate (co-amoxiclav) with that of placebo for women in
      spontaneous preterm labour and intact membranes, without overt signs of clinical
      infection, by use of a factorial randomised design. The aim of the present study-
      the ORACLE Children Study II--was to determine the long-term effects on children
      after exposure to antibiotics in this clinical situation. METHODS: We assessed
      children at age 7 years born to the 4221 women who had completed the ORACLE II
      study and who were eligible for follow-up with a structured parental
      questionnaire to assess the child's health status. Functional impairment was
      defined as the presence of any level of functional impairment (severe, moderate,
      or mild) derived from the mark III Multi-Attribute Health Status classification
      system. Educational outcomes were assessed with national curriculum test results
      for children resident in England. FINDINGS: Outcome was determined for 3196 (71%)
      eligible children. Overall, a greater proportion of children whose mothers had
      been prescribed erythromycin, with or without co-amoxiclav, had any functional
      impairment than did those whose mothers had received no erythromycin (658 [42.3%]
      of 1554 children vs 574 [38.3%] of 1498; odds ratio 1.18, 95% CI 1.02-1.37). Co
      amoxiclav (with or without erythromycin) had no effect on the proportion of
      children with any functional impairment, compared with receipt of no co-amoxiclav
      (624 [40.7%] of 1523 vs 608 [40.0%] of 1520; 1.03, 0.89-1.19). No effects were
      seen with either antibiotic on the number of deaths, other medical conditions,
      behavioural patterns, or educational attainment. However, more children whose
      mothers had received erythromycin or co-amoxiclav developed cerebral palsy than
      did those born to mothers who received no erythromycin or no co-amoxiclav,
      respectively (erythromycin: 53 [3.3%] of 1611 vs 27 [1.7%] of 1562, 1.93, 1.21
      3.09; co-amoxiclav: 50 [3.2%] of 1587 vs 30 [1.9%] of 1586, 1.69, 1.07-2.67). The
      number needed to harm with erythromycin was 64 (95% CI 37-209) and with co
      amoxiclav 79 (42-591). INTERPRETATION: The prescription of erythromycin for women
      in spontaneous preterm labour with intact membranes was associated with an
      increase in functional impairment among their children at 7 years of age. The
      risk of cerebral palsy was increased by either antibiotic, although the overall
      risk of this condition was low. FUNDING: UK Medical Research Council.

PMID- 18804277
TI  - A comparison of fatigue crack growth in human enamel and hydroxyapatite.
AB  - Cracks and craze lines are often observed in the enamel of human teeth, but they
      rarely cause tooth fracture. The present study evaluates fatigue crack growth in
      human enamel, and compares that to the fatigue response of sintered
      hydroxyapatite (HAp) with similar crystallinity, chemistry and density. Miniature
      inset compact tension (CT) specimens were prepared that embodied a small piece of
      enamel (N=8) or HAp (N=6). The specimens were subjected to mode I cyclic loads
      and the steady state crack growth responses were modeled using the Paris Law.
      Results showed that the fatigue crack growth exponent (m) for enamel (m=7.7+/
      1.0) was similar to that for HAp (m=7.9+/-1.4), whereas the crack growth
      coefficient (C) for enamel (C=8.7 E-04 (mm/cycle)x(MPa m(0.5))(-m)) was
      significantly lower (p<0.0001) than that for HAp (C=2.0 E+00 (mm/cycle)x(MPa
      m(0.5))(-m)). Micrographs of the fracture surfaces showed that crack growth in
      the enamel occurred primarily along the prism boundaries. In regions of
      decussation, the microstructure promoted microcracking, crack bridging, crack
      deflection and crack bifurcation. Working in concert, these mechanisms increased
      the crack growth resistance and resulted in a sensitivity to crack growth (m)
      similar to bone and lower than that of human dentin. These mechanisms of
      toughening were not observed in the crack growth response of the sintered HAp.
      While enamel is the most highly mineralized tissue of the human body, the
      microstructural arrangement of the prisms promotes exceptional resistance to
      crack growth.

PMID- 18804279
TI  - Cartilage regeneration with highly-elastic three-dimensional scaffolds prepared
      from biodegradable poly(L-lactide-co-epsilon-caprolactone).
AB  - Compressive mechanical stimuli are crucial in regenerating cartilage with tissue
      engineering, which creates a need for scaffolds that can maintain their
      mechanical integrity while delivering mechanical signals to adherent cells during
      strain applications. With these goals in mind, the aim of this study was to
      develop a mechano-active scaffold that facilitated effective cartilaginous tissue
      formation under dynamic physiological environments. Using a gel-pressing method,
      we fabricated a biodegradable and highly-elastic scaffold from poly(L-lactide-co
      epsilon-caprolactone) (PLCL; 5:5), with 85% porosity and a 300-500-microm pore
      size, and we compared it to control scaffolds made of rigid polylactide (PLA) or
      poly(lactide-co-glycolide) (PLGA). After tensile mechanical tests and recovery
      tests confirmed the elasticity of the PLCL scaffolds, we seeded them with rabbit
      chondrocytes, cultured them in vitro, and subcutaneously implanted them into nude
      mice for up to eight weeks. The PLCL scaffolds possessed a completely rubber-like
      elasticity, were easily twisted and bent, and exhibited an almost complete (over
      97%) recovery from applied strain (up to 500%); the control PLA scaffolds showed
      little recovery. In vitro and in vivo accumulations of extracellular matrix on
      the cell-PLCL constructs demonstrated that they could not only sustain but also
      significantly enhance chondrogenic differentiation. Moreover, the mechanical
      stimulation of the dynamic in vivo environment promoted deposition of the
      chondral extracellular matrix onto the PLCL. In contrast, on the PLA scaffolds,
      most of the chondrocytes had de-differentiated and formed fibrous tissues. In a
      rabbit defect model, the groups treated with PLCL scaffolds exhibited
      significantly enhanced cartilage regeneration compared to groups harboring an
      empty control or PLGA scaffolds. These results indicated that the mechano-active
      PLCL scaffolds effectively delivered mechanical signals associated with
      biological environments to adherent chondrocytes, suggesting that these elastic
      PLCL scaffolds could successfully be used for cartilage regeneration.

PMID- 18804278
TI  - Expansion of microvascular networks in vivo by phthalimide neovascular factor 1
      (PNF1).
AB  - Phthalimide neovascular factor (PNF1, formerly SC-3-149) is a potent stimulator
      of proangiogenic signaling pathways in endothelial cells. In this study, we
      evaluated the in vivo effects of sustained PNF1 release to promote ingrowth and
      expansion of microvascular networks surrounding biomaterial implants. The dorsal
      skinfold window chamber was used to evaluate the structural remodeling response
      of the local microvasculature. PNF1 was released from poly(lactic-co-glycolic
      acid) (PLAGA) films, and a transport model was utilized to predict PNF1
      penetration into the surrounding tissue. PNF1 significantly expanded
      microvascular networks within a 2mm radius from implants after 3 and 7 days by
      increasing microvessel length density and lumenal diameter of local arterioles
      and venules. Staining of histological sections with CD11b showed enhanced
      recruitment of circulating white blood cells, including monocytes, which are
      critical for the process of vessel enlargement through arteriogenesis. As PNF1
      has been shown to modulate MT1-MMP, a facilitator of CCL2 dependent leukocyte
      transmigration, aspects of window chamber experiments were repeated in CCR2(-/-)
      (CCL2 receptor) mouse chimeras to more fully explore the critical nature of
      monocyte recruitment on the therapeutic benefits of PNF1 function in vivo.

PMID- 18804280
TI  - A case of acute promyelocytic leukemia presenting with a nonleukemic granulocytic
      sarcoma of the ovary, with subsequent development of acute myeloid leukemia
      associated with t(8;21).

PMID- 18804281
TI  - Psychopathic personality traits and delinquent careers: an empirical examination.
AB  - PURPOSE: Few studies have simultaneously investigated psychopathic traits in
      relation to assorted dimensions of a delinquent career. The current study
      examined the role that psychopathy might play in facilitating research on the
      small subset of youth at risk for persistent antisocial behavior. METHOD: This
      study examined psychopathic personality scores using the Antisocial Process
      Screening Device (APSD) and the Psychopathic Personality Inventory-Short Version
      (PPI-SV) in a statewide population of 723 juvenile offenders. RESULTS:
      Psychopathy scores revealed a linear score-response such that higher psychopathy
      scores were associated with increases in general delinquency (including violent
      and non-violent forms), hostile aggression, and three forms of early onset
      delinquency, including offending, police contact, and juvenile court referral.
      Moreover, negative binomial regression, hierarchical linear regression, and
      logistic regression models revealed that psychopathy factors possessed utility in
      predicting all dimensions of the delinquent career net the effects of demographic
      and available risk factors. CONCLUSION: Psychopathy should be fully incorporated
      into criminological investigations of delinquent and criminal careers.

PMID- 18804282
TI  - Maternal transfer of organochlorines and brominated flame retardants in blue tits
      (Cyanistes caeruleus).
AB  - Although eggs have frequently been used as a biomonitoring tool for contamination
      with organohalogenated pollutants (OHPs), few studies have investigated the
      processes of maternal transfer in birds. Here, maternal transfer of
      polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs) and
      polybrominated diphenyl ethers (PBDEs) was investigated through comparison of the
      concentrations and profiles between whole homogenised female blue tits (Cyanistes
      caeruleus) and their eggs. In addition, we examined if there was an effect of
      laying order on the concentrations of PCBs, OCPs and PBDEs. PCBs were the most
      abundant contaminants in female blue tits and their eggs, followed by OCPs and
      PBDEs. Among the OCPs, p,p'-DDE was the most dominant compound and accounted for
      more than 80% of the sum OCPs. Egg concentrations decreased significantly in
      relation to the laying order from 1623+/-148 ng/g lipid weight (lw) to 1040+/-47
      ng/g lw for the sum PCBs, from 342+/-24 ng/g lw to 235+/-17 ng/g lw for the sum
      OCPs and from 49+/-5 ng/g lw to 27+/-5 ng/g lw for the sum PBDEs. When reviewing
      all studies investigating laying order effects of OHPs in birds, no clear
      patterns emerged, which may be due to differences in study species and
      methodology among studies. Despite the fact that there were laying order effects
      in blue tit clutches, the variance in concentrations of PCBs and PBDEs was larger
      among clutches than within clutches. Variance in OCP concentrations among
      clutches was similar to the variance within clutches. These results suggest that
      one randomly collected blue tit egg from a clutch is useful as biomonitoring tool
      for PCBs and PBDEs, while for OCPs it is recommended to consistently use the same
      egg from the laying sequence as a biomonitoring tool. Lipid-normalized
      concentrations of sum PCBs, sum OCPs and sum PBDEs in female blue tits after
      clutch completion were comparable to the concentrations in the first-laid eggs.
      The egg/female lipid concentration ratios for sum PCBs, sum OCPs and sum PBDEs
      decreased significantly from 1.0+/-0.09 to 0.7+/-0.003, 1.1+/-0.1 to 0.7+/-0.02
      and 1.2+/-0.14 to 0.8+/-0.05, respectively, during the course of egg laying. The
      profiles of the females and eggs differed significantly for the PCBs, OCPs and
      PBDEs. There was a higher contribution of lower chlorinated PCB congeners (CB 28,
      CB 52, CB 95, CB 101 and CB 110), BDE 183, p,p'-DDT and other less persistent
      OCPs in the females compared to their eggs. Maternal transfer in blue tits seemed
      to be selective for the more bioaccumulative and persistent congeners/compounds.

PMID- 18804283
TI  - Heat shock protein-antigen fusions lose their enhanced immunostimulatory capacity
      after endotoxin depletion.
AB  - Heat shock proteins (HSPs) induce cross-presentation of antigens by dendritic
      cells (DC) as well as DC maturation. These properties make HSP antigen complexes
      good candidates to prime CD8 T cell responses against tumor-associated antigens.
      In this study, we analyzed four different members of the HSP70 family fused to a
      fragment of ovalbumin (OVA) as a model tumor antigen. E. coli-derived recombinant
      HSP70-OVA fusion proteins efficiently primed antigen-specific cytotoxic T cells
      in short-term in vivo immunization assays. Because of concerns that the adjuvant
      effect of HSPs may be due to endotoxin contamination, we studied this issue in
      detail. Induction of OVA-specific cytotoxicity was significantly decreased in
      mice deficient for the LPS receptor, TLR4. After careful removal of endotoxins,
      immunization with HSP70-OVA failed to prime cytotoxic T cell responses. However,
      we obtained strong in vivo kill responses when endotoxin-depleted HSP70-OVA was
      used in combination with the TLR9 ligand CpG oligodeoxynucleotide 1668.
      Importantly, prophylactic and therapeutic treatment with endotoxin-depleted HSP70
      OVA together with CpG significantly delayed the outgrowth of OVA-expressing B16
      melanoma cells. However, we were unable to detect significant differences in the
      magnitudes of immune responses against endotoxin-depleted recombinant OVA vs.
      endotoxin-depleted HSP70-OVA fusion protein. Thus, immunization with recombinant
      HSP70-antigen fusion protein does not provide an advantage over recombinant
      antigen alone when combined with a suitable adjuvant. Altogether, our data
      suggest that the adjuvant effect of the HSP70 part of the fusion protein is
      completely lost after endotoxin removal.

PMID- 18804284
TI  - A missense variant (P10L) of the melanopsin (OPN4) gene in seasonal affective
      disorder.
AB  - BACKGROUND: Melanopsin, a non-visual photopigment, may play a role in aberrant
      responses to low winter light levels in Seasonal Affective Disorder (SAD). We
      hypothesize that functional sequence variation in the melanopsin gene could
      contribute to increasing the light needed for normal functioning during winter in
      SAD. METHODS: Associations between alleles, genotypes, and haplotypes of
      melanopsin in SAD participants (n=130) were performed relative to controls with
      no history of psychopathology (n=90). RESULTS: SAD participants had a higher
      frequency of the homozygous minor genotype (T/T) for the missense variant
      rs2675703 (P10L) than controls, compared to the combined frequencies of C/C and
      C/T. Individuals with the T/T genotype were 5.6 times more likely to be in the
      SAD group than the control group, and all 7 (5%) of individuals with the T/T
      genotype at P10L were in the SAD group. LIMITATIONS: The study examined only one
      molecular component of the non-visual light input pathway, and recruitment
      methods for the comparison groups differed. CONCLUSION: These findings support
      the hypothesis that melanopsin variants may predispose some individuals to SAD.
      Characterizing the genetic basis for deficits in the non-visual light input
      pathway has the potential to define mechanisms underlying the pathological
      response to light in SAD, which may improve treatment.

PMID- 18804285
TI  - Cognitive therapy for depressed adults with comorbid social phobia.
AB  - BACKGROUND: Evidence suggests that comorbid depression influences the outcome of
      cognitive-behavioral treatment for patients presenting with social phobia. Little
      is known, however, about the influence of comorbid social phobia on the response
      to cognitive therapy (CT) for depression among adults presenting with recurrent
      major depressive disorder (MDD). These analyses seek to clarify this
      relationship. METHODS: Patients (N=156) with recurrent DSM-IV MDD entered CT (20%
      also met DSM-IV criteria for social phobia). Every week during the course of CT,
      clinicians assessed depressive symptoms and patients completed self-report
      instruments measuring severity of depression and anxiety. RESULTS: At
      presentation, outpatients with comorbid social phobia reported greater levels of
      depressive symptoms and clinicians rated their impairment as more severe,
      compared to their counterparts without social phobia. Patients with or without
      comorbid social phobia did not differ significantly in (1) attrition rates; (2)
      response or sustained remission rates; (3) time to response or sustained
      remission; or (4) rate of improvement in symptoms of depression or anxiety.
      LIMITATIONS: The lack of domain-specific measures limits inference with respect
      to the improvements in social anxiety that occur with CT of depression.
      CONCLUSIONS: These findings introduce the hypothesis that CT for depression may
      be flexible enough to treat the depressive symptoms of patients presenting with
      MDD who also suffer from social phobia.

PMID- 18804286
TI  - Autoantibodies to folate receptor during pregnancy and neural tube defect risk.
AB  - Periconceptional folic acid can reduce the occurrence of neural tube defects
      (NTDs) by up to 70%, and autoantibodies for folate receptors (FRs) have been
      observed in serum from women with a pregnancy complicated by an NTD. This
      population-based cohort study has examined serum from pregnant mothers for
      autoantibodies to FRs, antibodies to bovine folate binding protein (FBP), and
      inhibition of folic acid binding to FR and FBP in association with NTD risk. The
      mid-gestational maternal serum specimens used for this study were collected
      during the 15-18th week of pregnancy. Samples were obtained from the California
      Birth Defects Monitoring Program; 29 mothers had a pregnancy complicated by spina
      bifida and 76 mothers had unaffected children. The presence of IgG and IgM
      antibodies to human FR, bovine FBP, and inhibition of folic acid binding to FR
      and FBP was determined. Higher activity of IgM to FBP in cases verses controls
      was observed (P=0.04). Higher activity of IgM and IgG autoantibodies to FR was
      observed (P<0.001 and P=0.04, respectively). Risk estimates at two standard
      deviations above average control antibody concentrations were OR=2.07 (CI=1.02,
      4.06) for anti-FBP IgM, OR=2.15 (CI=1.02, 4.69) for anti-FR IgG and OR=3.19
      (CI=1.47, 6.92) for anti-FR IgM. These data support the hypothesis that high
      titers of antibodies and blocking of folic acid binding to FRs by maternal serum
      should be regarded as risk factors for NTDs.

PMID- 18804287
TI  - Downregulation of IL-17 and IL-6 in the central nervous system by glatiramer
      acetate in experimental autoimmune encephalomyelitis.
AB  - T helper 17 (Th17) cells are pivotal in the immune pathogenesis of EAE.
      Glatiramer acetate (GA) can enhance Treg FOXp3 expression. We demonstrate that GA
      downregulates the expression of both IL-17 and IL-6 in two different EAE models.
      Increased mRNA expression in CNS for ROR gamma t, IL-17, IL-12/IL-23, IL-6, TNF
      alpha, STAT4 and Th1 cytokines were significantly reduced by GA with a
      concomitant rise in SMAD3. The increased expression of TNF-alpha, IL-6, and IL-17
      in CNS of CD25+ depleted animals was suppressed by GA treatment. This study
      demonstrates that both Th1 polarization and Th17 expression are modulated by GA.

PMID- 18804288
TI  - Identification and development of new therapeutics for multiple sclerosis.
AB  - In recent years, large efforts have been undertaken to establish new therapeutic
      options for the treatment of multiple sclerosis (MS). So far, all of these
      strategies more or less specifically target subsets of the immune response in MS,
      including not only activation and expansion of T cells, their circulation and
      transmigration over the blood-brain barrier but also other cell types such as B
      cells and probably also natural killer cells. Here, we review available data on
      the most promising (at present) new therapeutic approaches. These involve the
      orally available compounds cladribine, FTY720, fumaric-acid esters, laquinimod
      and teriflunomide in addition to the monoclonal antibodies alemtuzumab,
      daclizumab, natalizumab and rituximab. After successful completion of Phase III
      studies, these compounds might have the potential to add to the current
      therapeutic armentarium especially for relapsing remitting disease courses in the
      near future, possibly opening the way to a more individualized treatment.

PMID- 18804290
TI  - Transcriptomic responses of European flounder (Platichthys flesus) to model
      toxicants.
AB  - The temporal transcriptomic responses in liver of Platichthys flesus to model
      environmental pollutants were studied over a 16-day time span after
      intraperitoneal injection with cadmium chloride (50 microg/kg in saline), 3
      methylcholanthrene (25 mg/kg in olive oil), Aroclor 1254 (50 mg/kg in olive oil),
      tert-butyl-hydroperoxide (5 mg/kg in saline), Lindane (25mg/kg in olive oil),
      perfluoro-octanoic acid (100 mg/kg in olive oil) and their vehicles, olive oil (1
      ml/kg) or saline (0.9%). Statistical, gene ontology and supervised analysis
      clearly demonstrated the progression from acute effects, biological responses to
      and recovery from the treatments. Key biological processes disturbed by the
      individual treatments were characterised by gene ontology analyses and individual
      toxicant-responsive genes and pathways were identified by supervised analyses.
      Responses to the polyaromatic and chlorinated aromatic compounds showed a degree
      of commonality but were distinguishable and they were clearly segregated from the
      responses to the pro-oxidants cadmium and the organic hydroperoxide, as well as
      from the peroxisomal proliferator, perfluoro-octanoic acid. This study
      demonstrated the utility of the microarray technique in the identification of
      toxicant-responsive genes and in discrimination between modes of toxicant action.

PMID- 18804291
TI  - Reproductive toxicity of the water accommodated fraction (WAF) of crude oil in
      the polychaetes Arenicola marina (L.) and Nereis virens (Sars).
AB  - Accidental pollution incidents are common in the marine environment and are often
      caused by oil-related activities. Here the potential of such an incident to
      disrupt reproduction in two polychaete species is investigated, using an
      environmentally relevant preparation of weathered Forties crude oil, i.e. the
      water accommodated fraction (WAF). Oocytes were collected and exposed to three
      concentrations of WAF for 1h prior to the addition of sperm, so that
      fertilization took place under exposure conditions. Fertilization success was
      significantly reduced in both species by an exposure to WAF concentrations
      equivalent to 0.38 mgL(-1) PAHs, to just 26.8% in Arenicola marina compared to
      76% in Nereis virens. The effects of WAF exposure on fertilization were greatly
      enhanced at lower sperm concentrations in N. virens, with a complete lack of
      fertilization reactions observed at sperm concentrations of 10(3)sperm per mL. We
      therefore suggest a mechanism of toxicity related to sperm swimming behaviour,
      resulting in reduced sperm:egg collision rates. WAF was found to reduce post
      fertilization development rates and have teratogenic effects on early embryonic
      stages in both species, which exhibited abnormal cleavage patterns and high
      levels of fluctuating asymmetry. These results illustrate how the presence of
      crude oil in its soluble form in seawater at the time of a spawning event for
      either A. marina or N. virens could impact on fertilization success with
      implications for the fertilization ecology of these free spawning marine
      invertebrates.

PMID- 18804292
TI  - Sex reversal of the amphibian, Xenopus tropicalis, following larval exposure to
      an aromatase inhibitor.
AB  - Aromatase is a steroidogenic enzyme that catalyzes the conversion of androgens to
      estrogens in vertebrates. Modulation of this enzyme's activity by xenobiotic
      exposure has been shown to adversely affect gonad differentiation in a number of
      diverse species. We hypothesized that exposure to the aromatase inhibitor,
      fadrozole, during the larval development of the tropical clawed frog, Xenopus
      tropicalis, would result in masculinization of the developing female gonad.
      Tadpoles were exposed to fadrozole at nominal concentrations from 1 to 64
      microg/L in a flow-through system from < 24 h post-fertilization (Nieuwkoop Faber
      (NF) stage 15-20) to metamorphosis (NF stage 66). At metamorphosis,
      morphologically examined gonads indicated complete masculinization of all
      tadpoles at concentrations of 16 microg/L and above and a significant bias in sex
      ratio towards males at concentrations of 1 microg/L and above. No effects on time
      to metamorphosis, body mass, or body length were observed. A random subsample of
      frogs was raised to reproductive maturity (39 weeks post-fertilization) in
      control water. All frogs exposed as tadpoles to 16 microg/L fadrozole or greater
      possessed testes at sexual maturity. Intersexed gonads characterized by the
      presence of both testicular and ovarian tissue were observed in 12% of frogs in
      the 4 microg/L treatment. No differences in estradiol, testosterone, or
      vitellogenin plasma concentrations were observed in exposed males or females
      compared to controls. Females in the 4 microg/L treatment possessed a
      significantly greater percentage of pre-vitellogenic oocytes than controls and
      were significantly smaller in body mass. No differences in sperm counts were
      observed in exposed males compared to controls. Results from this study
      demonstrate that larval exposure to an aromatase inhibitor can result in the
      complete masculinization of female gonads. These masculinized females are
      phenotypically indistinguishable from normal males at adulthood. Lower levels of
      aromatase inhibition resulted in intersexed gonads and possible female
      reproductive impairment at adulthood. These results indicate that exposure of
      amphibians to xenobiotics capable of inhibiting aromatase would result in adverse
      reproductive consequences.

PMID- 18804293
TI  - Glutathione transferases from Anguilla anguilla liver: identification, cloning
      and functional characterization.
AB  - Glutathione transferases (GSTs) constitute a class of detoxifying enzymes
      involved in Phase II metabolism. Using GSH-affinity chromatografy followed by
      HPLC analysis, two GST isoforms were isolated from the Anguilla anguilla liver
      cytosol. The major GST belongs to the piscine-specific rho class and accounted
      for about 59% of total GST affinity eluted fraction, while the remaining 41% was
      represented by a Pi class GST. Both isoforms were cloned, heterologously
      expressed in Escherichia coli and their enzyme activities were characterized with
      respect to a broad spectrum of well-known GST substrates. Our data indicate that
      only a fraction of prototypical GST substrates are conjugated by these enzymes
      and that Pi class GST has higher specific activity than rho class GST against 1
      chloro-2,4-dinitrobenzene (CDNB), ethracrynic acid, 4-nitroquinoline-1-oxide and
      p-nitrophenyl acetate while trans-2-nonenal is detoxified more efficiently by rho
      class GST. Analysis of the kinetics parameters of the conjugation against CDNB
      indicated that the utilization ratio K(cat)/K(m) is slightly higher for rho class
      GST with respect to pi class GSTs. Finally, to determine the potential for
      environmental inhibition of the GST isoforms, we examined the effect of the
      widely used herbicide atrazine as an inhibitor of catalytic activity. The
      inhibition studies revealed that atrazine was an effective inhibitor of GST-CDNB
      catalytic activities of both isoforms at micromolar concentrations, suggesting
      the sensitivity of these isoforms to pesticide inhibition at environmentally
      relevant concentrations.

PMID- 18804294
TI  - Sensitivity of brown trout reproduction to long-term estrogenic exposure.
AB  - A decline in brown trout (Salmo trutta fario) catches has been reported in
      Switzerland, but at present the causative factors have not been clearly
      identified. Estrogen-active endocrine disrupters (EEDs) have been suggested as
      one possible explanation, since they are widespread in the aquatic environment
      and often found at elevated concentrations. In the present study the effects of
      long-term estrogenic exposure on the reproductive capability of brown trout were
      investigated. Adult fish were continuously exposed to an environmentally relevant
      mixture of the natural estrogens estrone (E1), 17beta-estradiol (E2) and the
      xenoestrogen 4-nonylphenol (NP); the average measured concentrations over the
      entire exposure time (n=9) were 14.0 ng/l (Min 8.1 and Max 20.6) for E1, 2.1 ng/l
      (Min 1.3 and Max 4.1) for E2 and 111.0 ng/l (Min 106.7 and Max 115.9) for NP. A
      solvent control served as negative control, and up to 10-fold higher mixture
      concentration than the environmentally relevant concentration served as positive
      control. The fish were exposed for 150 days from the onset of gonadal
      recrudescence until sexual maturation. Plasma vitellogenin (Vtg) was
      significantly induced by both concentrations of the estrogenic mixture, whereas
      effects on growth and fertility were only observed in fish exposed to the high
      mixture treatment. Fertilization success and offspring hatchability in brown
      trout exposed to the high mixture treatment were significantly reduced to 9% and
      6%, respectively. Developmental time from fertilization until hatching, the
      percentage of larvae with malformations and survival of larvae, however, were not
      affected. The results suggest that a combination of estrogen-active compounds at
      environmentally relevant concentrations would not adversely affect those
      parameters of brown trout reproductive capability measured in this study. Plasma
      Vtg in male brown trout appeared to be more sensitive to (xeno)estrogen exposure
      than the measured reproductive effects.

PMID- 18804295
TI  - Long-term outcome of percutaneous coronary intervention for unprotected left main
      coronary artery disease.
AB  - OBJECTIVES: The aim of this study is to evaluate the in-hospital, 30 day and long
      term outcomes after percutaneous coronary intervention for unprotected left main
      coronary artery disease. BACKGROUNDS: Left main coronary artery (LMCA) diseases
      stenosis is a strong indication for coronary artery bypass grafting (CABG). With
      improved device technology, percutaneous coronary intervention (PCI) with drug
      eluting stent (DES) stents had been recently advocated as an alternative
      procedure for the unprotected LMCA disease. METHODS: Between January 2003 and
      February 2007, all unprotected LMCA PCI procedures were retrospectively
      collected. Outcomes were obtained by chart record review and telephone interview.
      RESULTS: Fifty five consecutive patients with >50% diameter stenosis of LMCA
      undergoing PCI were analyzed. Indications for a percutaneous strategy were
      prohibitive surgical risks, or patient/physician preference. The procedural
      success rate was 98%. 41 patients (75%) received DES implantation. The majority
      of cases (n=33) were treated with a double-stent strategy. There were no in
      hospital deaths. The clinical follow-up time was 867+/-410 days (range 20-1715).
      18 (29%) patients experienced major adverse cardiac events, including 3 (5%)
      deaths, 4 (7%) myocardial infarctions, and 12 (21.8%) target lesion
      revascularizations (TLR) during follow-up. Multivariate analysis revealed
      hyperlipidemia (Hazard ratio, HR=6.2, p=0.024) and bifurcation involvement
      (HR=4.4, p=0.008) were independent predictors for MACE. CONCLUSIONS: Our results
      showed that PCI with stenting was an acceptable treatment option for patients
      with LMCA stenosis. Involvement of the LMCA bifurcation remains a predictor for
      unfavorable outcome.

PMID- 18804296
TI  - Dyslipidemia and abdominal aortic aneurysm: another piece of the puzzle?
AB  - The underlying cause of aneurysmal aortic dilation is uncertain in most patients.
      It is unclear whether atherosclerosis causes aneurysmal disease or vice versa,
      while familial clusters are suggestive of a possible genetic predisposition. The
      data obtained from well-designed molecular and clinical studies support a
      multifactorial, systemic, nonatherosclerotic causal hypothesis, such as a defect
      in vascular structural proteins, with atherosclerosis occurring as a secondary
      process.

PMID- 18804297
TI  - Fluorescence complementation: an emerging tool for biological research.
AB  - Numerous technologies based on utilizing fluorescent proteins have been developed
      for biological research, and fluorescence complementation (FC) is a recent
      application for visualization of molecular events in living cells and organisms.
      Currently, ten fluorescent proteins have been demonstrated to support FC. Over
      the past five years, FC-based technologies have been developed to visualize a
      variety of molecular events, such as protein-protein interactions, post
      translational modifications, protein folding, conformational changes, RNA-protein
      interactions, mRNA localization and DNA hybridization. In addition, FC has also
      been used for drug discovery. These applications are providing fascinating
      insights into many biological processes. Here, we review the principles and
      applications of FC technologies, discuss their current challenges and examine
      prospects for future advances.

PMID- 18804298
TI  - Nanoparticles as vehicles for delivery of photodynamic therapy agents.
AB  - Photodynamic therapy (PDT) in cancer treatment involves the uptake of a
      photosensitizer by cancer tissue followed by photoirradiation. The use of
      nanoparticles as carriers of photosensitizers is a very promising approach
      because these nanomaterials can satisfy all the requirements for an ideal PDT
      agent. This review describes and compares the different individual types of
      nanoparticles that are currently in use for PDT applications. Recent advances in
      the use of nanoparticles, including inorganic oxide-, metallic-, ceramic-, and
      biodegradable polymer-based nanomaterials as carriers of photosensitizing agents,
      are highlighted. We describe the nanoparticles in terms of stability,
      photocytotoxic efficiency, biodistribution and therapeutic efficiency. Finally,
      we summarize exciting new results concerning the improvement of the photophysical
      properties of nanoparticles by means of biphotonic absorption and upconversion.

PMID- 18804300
TI  - Impact of homologous recombination on individual cellular radiosensitivity.
AB  - PURPOSE: Individual radiosensitivity as measured with in vitro irradiated
      lymphocytes using metaphase analysis can predict the risk of normal tissue
      effects after radiotherapy. This parameter is considered to be primarily
      determined by the cellular repair capacity of DNA double-strand breaks (DSBs). It
      is now tested to which extent this capacity also depends on homologous
      recombination (HR), which is a pathway available when cells are in S/G2 phase.
      METHODS: Experiments were performed with CHO K1 cells, in which HR was suppressed
      via knock-down of RAD51 using RNA interference (RNAi). RAD51 was measured via
      western and foci formation, cell survival by colony forming, DSBs by gammaH2AX
      foci formation, and chromosomal damage using PCC, G0 or G2 assay. RESULTS: In
      quiescent G1 cells DSB repair is completed 6h after irradiation. But there is
      still a substantial fraction of non-repaired DSBs. Most of these DSBs are
      repaired when G1 cells are stimulated into cell cycle. Suppression of HR by down
      regulation of RAD51 did not affect this repair. In contrast, repair was inhibited
      when cells were irradiated in late S/G2. In line with these data down-regulation
      of HR did affect survival of cells irradiated in late S/G2, but not in G1.
      CONCLUSIONS: Individual radiosensitivity as measured for G0/1 cells using
      metaphase analysis does not depend on homologous recombination.

PMID- 18804301
TI  - Effect of body mass index on shifts in ultrasound-based image-guided intensity
      modulated radiation therapy for abdominal malignancies.
AB  - BACKGROUND AND PURPOSE: We investigated whether corrective shifts determined by
      daily ultrasound-based image-guidance correlate with body mass index (BMI) of
      patients treated with image-guided intensity-modulated radiation therapy (IG
      IMRT) for abdominal malignancies. The utility of daily image-guidance,
      particularly for patients with BMI>25.0, is examined. MATERIALS AND METHODS:
      Total 3162 ultrasound-directed shifts were performed in 86 patients. Direction
      and magnitude of shifts were correlated with pretreatment BMI. Bivariate
      statistical analysis and analysis of set-up correction data were performed using
      systematic and random error calculations. RESULTS: Total 2040 daily alignments
      were performed. Average 3D vector of set-up correction for all patients was
      12.1mm/fraction. Directional and absolute shifts and 3D vector length were
      significantly different between BMI cohorts. 3D displacement averaged 4.9
      mm/fraction and 6.8mm/fraction for BMI < or = 25.0 and BMI>25.0, respectively.
      Systematic error in all axes and 3D vector was significantly greater for
      BMI>25.0. Differences in random error were not statistically significant.
      CONCLUSIONS: Set-up corrections derived from daily ultrasound-based IG-IMRT of
      abdominal tumors correlated with BMI. Daily image-guidance may improve precision
      of IMRT delivery with benefits assessed for the entire population, particularly
      patients with increased habitus. Requisite PTV margins suggested in the absence
      of daily image-guidance are significantly greater in patients with BMI>25.0.

PMID- 18804302
TI  - Study on the synergic effect of natural compounds on the microbial quality decay
      of packed fish hamburger.
AB  - The effectiveness of natural compounds in slowing down the microbial quality
      decay of refrigerated fish hamburger is addressed in this study. In particular,
      the control of the microbiological spoilage by combined use of three
      antimicrobials, and the determination of their optimal composition to extend the
      fish hamburger Microbiological Stability Limit (MAL) are the main objectives of
      this work. Thymol, grapefruit seed extract (GFSE) and lemon extract were tested
      for monitoring the cell growth of the main fish spoilage microorganisms
      (Pseudomonas fluorescens, Photobacterium phosphoreum and Shewanella
      putrefaciens), inoculated in fish hamburgers, and the growth of mesophilic and
      psychrotrophic bacteria. A Central Composite Design (CCD) was developed to
      highlight a possible synergic effect of the above natural compounds. Results
      showed an increase in the MAL value for hamburgers mixed with the antimicrobial
      compounds, compared to the control sample. The optimal antimicrobial compound
      composition, which corresponds to the maximal MAL value determined in this study,
      is: 110 mgL(-1) of thymol, 100 mgL(-1) of GFSE and 120 mgL(-1) of lemon extract.
      The presence of the natural compounds delay the sensorial quality decay without
      compromising the flavor of the fish hamburgers.

PMID- 18804303
TI  - Cryptic subspecies and beauvericin production by Fusarium subglutinans from
      Europe.
AB  - Fusarium subglutinans is a maize ear rot pathogen and producer of beauvericin and
      other mycotoxins. This species has recently been split into two major
      phylogenetic within-species groups based on RFLP DNA sequence polymorphisms
      identified in the histone H3 and beta-tubulin sequences. A Pan European
      collection of the fungus originating mostly from maize was subjected to
      phylogenetic analysis by RFLP grouping and to chemical analysis for beauvericin
      production. Of the 62 isolates belonging to Group 1, 48 (77%) produced from 10 to
      532 microg/g of beauvericin, whereas none of the 39 Group 2 isolates synthesized
      detectable amounts of the mycotoxin. The association between RFLP group and
      beauvericin production is consistent with the existence of two reproductively
      isolated subgroups within F. subglutinans and indicates that the toxicological
      risk of isolates of F. subglutinans depends on the group with which they are
      affiliated.

PMID- 18804304
TI  - Maximal and submaximal treadmill tests in a young adult with fragile-X syndrome.
AB  - Fragile X syndrome is associated with expansion of a CGG triplet repeat in the
      FMR1 gene, which abolishes production of the FMRP protein. This abnormality is
      expressed as a number of neuro-endocrine disorders (the adrenal axis,
      macroorchidism) and the emergence of significant behavioural stress. Here, we
      report on the hormonal status of a young adult with fragile X syndrome, with a
      focus on catecholamine and cortisol changes during a submaximal treadmill test.
      The patient showed abnormally high epinephrine and norepinephrine concentrations.
      During a submaximal incremental test, cortisol levels were higher than the
      laboratory reference range. Although the submaximal incremental test has a
      significant "stressful" effect, this young adult was able to complete the entire
      protocol without any maladaptive behaviour or withdrawal.

PMID- 18804305
TI  - Incidence of type 1 and type 2 diabetes in adults and children in Kronoberg,
      Sweden.
AB  - All newly diagnosed diabetes in Kronoberg during 3 years was registered, with
      blood samples from 1630/1666 (97.8%) adults. Those positive for GADab and/or ICA
      and/or C-peptide<0.25nmol/L (0.7%) were classified as type 1 diabetes, the
      remaining as type 2. Incidence of type 1 in 0-19-year-olds was 37.8(36.1-39.6,
      95%CI) and in 20-100 year-olds 27.1(25.6-27.4) per 100 000 and year, it was
      bimodal with equal peaks in 0-9 year-olds and in 50-80-year-olds. Adults had type
      2 incidence 378 (375-380), children 3.1 (2.6-3.6). Among adults 6.9% had type 1
      and 93.1% type 2. Among antibodypositive adults (n=101), GADab were present in
      90%, ICA in 71%, both GADab and ICA in 61%. Ophthalmology contact as second
      source was confirmed for 98%. There were no gender differences in type 1 in any
      age group, small ones in pediatric subgroups. In type 2 men predominated in ages
      above 40 years. Incidences of type 1 diabetes in both children and adults were
      very high and as high above age 50 years as in children. Incidence of type 2 was
      the highest reported from Sweden, to which new diagnostic criteria, a high degree
      of case-finding, and many elders, may have contributed, but results may also
      reflect a true increase in incidence of both types of diabetes.

PMID- 18804306
TI  - A family history of type 2 diabetes is associated with glucose intolerance and
      obesity-related traits with evidence of excess maternal transmission for obesity
      related traits in a South East Asian population.
AB  - AIM: To evaluate family history (FH) of type 2 diabetes (T2DM) as a risk factor
      for impaired fasting glucose (IFG), impaired glucose tolerance (IGT), T2DM and
      related metabolic traits in South East Asia and to compare the effects of a
      paternal versus maternal history. METHODS: We studied 4717 men and women (68%
      Chinese, 18% Malays and 14% Asian Indians) living in Singapore. FH was considered
      positive if at least one first degree relative had T2DM. Obesity, fasting lipids,
      glucose and insulin levels were measured for all subjects. Insulin resistance
      (IR) was estimated by homeostasis model assessment (HOMA). An oral glucose
      tolerance test was carried for all subjects except those on diabetes medication.
      RESULTS: A positive FH was associated with increased risk of IFG/IGT (OR=1.67,
      95% CI=1.42-1.97) and T2DM (OR=2.95, 95% CI=2.36-3.70) as well as higher levels
      of obesity, HOMA-IR, fasting triglyceride (TG), and lower levels of high density
      lipoprotein (HDL) cholesterol and HOMA-beta. A maternal history of T2DM appeared
      to have a greater impact on obesity-related traits than a paternal history of
      T2DM. Compared to individuals with no FH of T2DM, a maternal history was
      associated with (i) greater body mass index (BMI) (24.15kg/m(2) vs. 23.42kg/m(2),
      p=0.016) and waist-to-hip ratio (WHR) (0.874 vs. 0.865, p=0.037) in men; and (ii)
      greater WHR (0.788 vs. 0.779, p=0.004), fasting triglyceride (1.23mmol/L vs.
      1.09mmol/L, p<0.001), HOMA-IR (2.02 vs. 1.75, p<0.001), fasting plasma glucose
      (5.25mmol/L vs. 5.18mmol/L, p=0.005) and 2-h plasma glucose (6.01mmol/L vs.
      5.78mmol/L, p=0.001) and lower HDL-C (1.41mmol/L vs. 1.47mmol/L, p=0.031) in
      women. CONCLUSION: T2DM appears to be heritable in South East Asians with excess
      maternal transmission of obesity, IR and dyslipidemia.

PMID- 18804307
TI  - Nitric oxide and vascular remodeling modulate hepatic arterial vascular
      resistance in the isolated perfused cirrhotic rat liver.
AB  - BACKGROUND/AIMS: Hepatic arterial resistance is modulated by the hepatic
      arterioles but the role of NO and vascular remodeling in hepatic arterial
      resistance in cirrhosis is unknown. METHODS: Cirrhosis was induced by CCl(4) or
      BDL. Using a bivascular liver perfusion dose-responses curves to methoxamine were
      obtained from the hepatic artery in absence and presence of L-NMMA. Lumen
      diameter, wall thickness and number of smooth muscle nuclei were quantitated in
      the arteries using image analysis. RESULTS: Hepatic arterial resistance and the
      response to methoxamine were lower in cirrhosis compared to controls (p< or =
      0.04) and lower in BDL compared to CCl(4) (p< or = 0.01). L-NMMA increased the
      response to methoxamine in CCl(4) (p=0.002) and BDL (p=0.05) but corrected the
      response only in CCl(4) (p=n.s. vs. control). Wall thickness and the number of
      smooth muscle nuclei were significantly smaller in cirrhosis compared to controls
      (p<0.05) and the number of nuclei was also lower in BDL compared to CCl(4)
      (p=0.005). CONCLUSIONS: NO is the main modulator of hepatic arterial resistance
      in CCl(4) but not in BDL. Intrahepatic arterial remodeling is present in both
      cirrhotic models but is greater in BDL. This indicates a larger role of
      structural changes in the control of hepatic arterial resistance in BDL.

PMID- 18804308
TI  - Branched-chain amino acids antagonism in patients with cirrhosis and a simulated
      upper GI bleed.

PMID- 18804309
TI  - Does the presence of adefovir-resistant variants lead to failure of tenofovir
      monotherapy?

PMID- 18804310
TI  - Interleukin-6-producing undifferentiated thymic carcinoma with neuroendocrine
      features.
AB  - Undifferentiated thymic carcinoma is a rare tumor of the thymus. Due to the
      extreme rarity of undifferentiated thymic carcinoma, very limited information
      about its characteristics is available. We encountered an autopsy case of a 33
      year-old woman diagnosed as having an undifferentiated thymic carcinoma with a
      high inflammatory response. The patient's serum interleukin-6 (IL-6) was elevated
      to 1930 pg/ml, and immunohistochemical staining of the carcinoma cells was
      positive for neuroendocrine markers and IL-6. To the best of our knowledge, this
      is the first report of an IL-6-producing undifferentiated thymic carcinoma with
      neuroendocrine features that shows a novel potential to produce IL-6.

PMID- 18804311
TI  - Response of nitrogen fixation in relation to nodule carbohydrate metabolism in
      Medicago ciliaris lines subjected to salt stress.
AB  - The effect of salt stress on nitrogen fixation, in relation to sucrose transport
      towards nodules and other sink organs and the potential of sucrose breakdown by
      nodules, was investigated in two lines of Medicago ciliaris. Under salt stress
      conditions, the two lines showed a decrease of total biomass production, but TNC
      1.8 was less affected by salt than TNC 11.9. The chlorophyll content was not
      changed in TNC 1.8, in contrast to TNC 11.9. Shoot, root, and nodule biomass were
      also affected in the two lines, but TNC 1.8 exhibited the higher potentialities
      of biomass production of these organs. Nitrogen fixation also decreased in the
      two lines, and was more sensitive to salt than growth parameters. TNC 1.8
      consistently exhibited the higher values of nitrogen fixation. Unlike nodules,
      leaves of both lines were well supplied in nutrients with some exceptions.
      Specifically, the calcium content decreased in the sensitive line leaves, and the
      nodule magnesium content was not changed in either line. The tolerant line
      accumulated more sodium in its leaves. The two lines did not show any differences
      in the nodule sodium content. Sucrose allocation towards nodules was affected by
      salt in the two lines, but this constraint did not seem to affect the repartition
      of sucrose between sink organs. Salt stress induced perturbations in nodule
      sucrolytic activities in the two lines. It inhibited sucrose synthase, but the
      inhibition was more marked in TNC 11.9; alkaline/neutral activity was not altered
      in TNC 1.8, whereas it decreased more than half in TNC 11.9. Thus, the relative
      tolerance of TNC 1.8 to salt stress could be attributed to a better use of these
      photoassimilates by nodules and a better supply of bacteroids in malate. The
      hypothesis of a competition for sucrose between nodules and other sink organs
      under salt stress could not be verified.

PMID- 18804312
TI  - Heterogeneity of skin manifestations in patients with Carney complex.
AB  - BACKGROUND: Carney complex is an autosomal dominant endocrine disorder associated
      with skin involvement. OBJECTIVE: To describe the dermatological signs of
      patients diagnosed with Carney complex (CNC) or primary pigmented adrenocortical
      nodular disease (PPNAD). METHODS: We conducted a prospective, single-center
      descriptive study of inpatients and outpatients at a university hospital
      endocrinology department. Sixteen patients from 14 families diagnosed with CNC or
      PPNAD were prospectively included in the study between September 2003 and March
      2006. Data collected were age at enrollment; sex; Fitzpatrick skin phototype; the
      presence, location, and density of classic CNC skin lesions--lentigines,
      freckles, blue nevi, cutaneous myxoma--and other non-disease-specific skin
      lesions. Histopathologic analysis was carried out in cases in which the lesions
      were thought to be degenerative or to confirm the diagnosis. Patients were
      systematically assessed for endocrine and visceral involvement and genotyped for
      the PRKAR1A gene. RESULTS: Twelve patients had lentiginosis (75%), 7 patients had
      blue nevi (43%), and 5 patients had cutaneous myxoma (31%). Patients could be
      classified into 3 groups based on skin signs: patients with no prominent skin
      lesions (n = 3), patients with skin lesions that could not be directly linked to
      CNC (n = 4), and patients with cutaneous lesions suggestive of CNC (n = 9). We
      found a correlation between dermatological and endocrine signs in 3 groups of
      patients: patients with few lesions, patients with an intermediate phenotype, and
      patients with both many endocrine signs and dermatological signs. LIMITATIONS:
      The classification proposed in our study should be validated on more patients.
      CONCLUSIONS: Skin manifestations are heterogeneous in patients with CNC, and skin
      phenotype seems to be correlated with endocrine phenotype.

PMID- 18804313
TI  - A facile synthesis of novel biologically active 4-hydroxy-N'-(benzylidene)-2H
      benzo[e][1,2]thiazine-3-carbohydrazide 1,1-dioxides.
AB  - A novel series of potentially biologically active 4-hydroxy-N'-(benzylidene)-2H
      benzo[e][1,2]thiazine-3-carbohydrazide 1,1-dioxides were synthesized starting
      from ultrasonic mediated N-alkylation of sodium saccharin with methyl
      chloroacetate. Ring expansion of methyl(1,1-dioxido-3-oxo-1,2-benzisothiazol
      2(3H)-yl)acetate followed by its hydrazinolysis afforded 4-hydroxy-2H-1,2
      benzothiazine-3-carbohydrazide 1,1-dioxide which was reacted in a straight
      forward manner with various benzaldehydes in an ultrasonic bath to get the title
      compounds. All of the synthesized compounds were subjected to preliminary
      evaluation for their antibacterial and DPPH radical scavenging activities.

PMID- 18804314
TI  - [Pathogenesis of primary large vessel arteritis].
AB  - Giant cell arteritis (GCA) and Takayasu's arteritis (TA) are the two primary
      large-vessel arteritides. Recent advances in cellular immunology have allowed
      better understanding of pathogenesis of these diseases. In GCA and TA, resident
      adventitial dendritic cells are activated by unidentified stimuli. This
      activation induces chemokine synthesis which enhances recruitment of inflammatory
      cells. T-cells infiltrate the vascular wall and specifically recognize one or a
      few antigens presented by shared epitopes associated with specific HLA molecules
      on dendritic cells. Activated T-cells produce IFNgamma stimulating two distinct
      populations of macrophages. Macrophages located in the intima produce pro
      inflammatory cytokines (IL-1, IL-6). Macrophages located in the media
      differentiate into giant cells and/or produce reactive oxygen species, nitric
      oxide and matrix metallo-proteinases. Macrophages of the media also produce VEGF,
      which leads to neovascularization and PDGF, which induces intimal hyperplasia and
      vascular occlusion. In TA, cytotoxic T cells infiltrate the vascular wall and
      induce apoptosis of the vascular cells. Better understanding of the pathogenesis
      of large-vessel arteritis may lead to development of immunosuppressive drugs
      specifically targeting the immunological mechanisms implicated in GCA and TA.

PMID- 18804315
TI  - Transposing Yallom: recognizing and understanding group dynamics in a Canadian
      online diploma in psychiatric nursing.
AB  - Given the historical association between psychiatric/mental health (P/MH) nursing
      education and group formats, and the recent shift to online education, one might
      expect to see a well developed literature that focuses on P/MH nurse education in
      online group settings; yet this is patently not the case. This paper attempts to
      redress this omission by drawing on educational material produced in a regional
      online diploma in psychiatric nursing. After reviewing the relevant extant
      literature, it adopts Yallom's seminal work and transposes this into online group
      settings. Examples of postings drawn from this programme are then used to help
      recognize and understand online group dynamics. The authors conclude that group
      dynamics are as much a part of online P/MH nurse education as they have been for
      'traditional', face-to-face, educational programs, albeit manifest, expressed and
      encountered in different ways. Secondly, acknowledging the existence of these
      group dynamics creates the need for a new skill set, or maybe the transposition
      of an existing skill set for P/MH nursing educators. Thirdly,
      examination/analysis of student online postings (virtual case studies) enables
      the tentative epistemological transposition of face-to-face group dynamics into
      the online version.

PMID- 18804316
TI  - An unusual cause of Frey syndrome.
AB  - We present the case of a young woman who complained of gustatory sweating of the
      skin of the submandibular region after resection for oral cancer, neck dissection
      and reconstruction with a radial forearm free flap. This is unusual after neck
      dissection and particularly so after selective neck dissection that did not need
      adjunctive radiotherapy.

PMID- 18804317
TI  - Need for and consequences of episiotomy in vaginal birth: a critical approach.
AB  - OBJECTIVE: to describe and explain the short-term effects of lateral episiotomy,
      and determine the factors associated with more/less common use of episiotomy.
      DESIGN: prospective cross-sectional survey using a postal questionnaire. SETTING:
      the study was conducted at two university hospitals and one regional hospital in
      Finland between October and December 2006. The hospitals were chosen using
      cluster sampling. The sample consisted of 1000 vaginal births, and data were
      collected using questionnaires which were completed by midwives or student
      midwives. The overall response rate was 88%. PARTICIPANTS: midwives or student
      midwives who took care of the women in labour provided information about
      childbearing women (n=879), obstetric factors and details of staff experience.
      FINDINGS: episiotomies were more common among primiparous than multiparous women
      (55% vs 12%, p0.001). More common use of episiotomy was also associated with
      induced births compared with spontaneous births in primiparous women (66% vs 53%,
      p=0.036), assisted vaginal births in all women (89% vs 25%, p0.001), and a
      prolonged active second stage of labour and epidural analgesia (17% vs 10%,
      p=0.036) in multiparous women. Correspondingly, episiotomies were less common
      among primiparous (44% vs 57%, p=0.041) and multiparous (7% vs 16%, p=0.003)
      women using spontaneous pushing compared with coached pushing. In the active
      second stage of labour, alternative birth positions (lateral, squatting, all
      fours, sitting) were associated with less common use of episiotomy than half
      sitting or lithotomy positions among primiparous women (22% vs 48% vs 85%,
      p0.001). There were no differences between primiparous women with and without
      episiotomy in low Apgar score at 1minute (10.6% vs 6.4%, p=0.131) or 5minutes
      (1.8% vs 1.1%, p=0.557), or between multiparous women with and without episiotomy
      in low Apgar score at 1minute (1.9% vs 2.2%, p=0.855) or 5minutes (0% vs 0.5%,
      p=0.603). There were more first- and second-degree perineal injuries as well as
      injuries to the vagina, labia minora and urethra in births performed without
      episiotomies among primiparous women (p0.001). Correspondingly, third-degree
      perineal injuries were more common if episiotomy was performed in both
      primiparous (2.2% vs 1.6%) and multiparous women (3.7% vs 0%). The maternity
      hospital was the most significant determinant of the episiotomy rate (odds ratio
      1 vs 1.9 vs 2.6, p=0.049). KEY CONCLUSIONS: episiotomy rates can be reduced
      without causing harm to women or newborn babies. Episiotomies can be avoided if
      induction and vacuum assistance are used sparingly, and if spontaneous pushing
      techniques and alternative birth positions (lateral, sitting, squatting, all
      fours) are used more often during labour.

PMID- 18804318
TI  - Detection of phosphorus species in sediments of artificial landscape lakes in
      China by fractionation and phosphorus-31 nuclear magnetic resonance spectroscopy.
AB  - Phosphorus (P) pollution in the sediments of seven artificial landscape lakes was
      studied via fractionation and phosphorus-31 nuclear magnetic resonance ((31)P
      NMR) spectroscopy. The lake sediments accumulated significant amounts of P from
      supplementation with reclaimed water and from runoff from the golf course lawns.
      The differences in total sediment P among lakes were correlated to the varied
      pollution extent from the lawns. One striking feature of the artificial lake
      sediments was the insufficiency of NaOH-extracted Al, which plays an important
      role in avoiding internal P release during anoxia. Another characteristic was the
      dominance of orthophosphate in the NaOH-EDTA extractants of the sediments, due to
      the heavy external P pollution. Phytate, considered prevalent in many soils and
      lake sediments, as well as polyphosphates and phosphonates which have appeared in
      some natural lake sediments, was not detected. The rank order of present biogenic
      P species was monoester-P>DNA-P>pyrophosphate>lipid-P.

PMID- 18804319
TI  - Editors' highlights.

PMID- 18804320
TI  - High-pressure study on bilayer phase behavior of oleoylmyristoyl- and
      myristoyloleoyl-phosphatidylcholines.
AB  - We investigated the thermotropic and barotropic bilayer phase behavior of 1
      myristoyl-2-oleoyl-sn-glycero-3-phosphocholine (MOPC) and 1-oleoyl-2-myristoyl-sn
      glycero-3-phosphocholine (OMPC) by means of the differential scanning calorimetry
      (DSC) and high-pressure light-transmittance technique. Water could be used as a
      solvent for measurements at high pressures because of the elevation of the
      transition temperatures above 0 degrees C by pressurization, whereas aqueous 50
      wt.% ethylene glycol solution was used mainly for those at low pressures. Only
      one phase transition was observed in the DSC thermogram of the MOPC bilayer
      membrane as an endothermic peak, and also observed at high pressures as an abrupt
      change of the light-transmittance. The transition was assigned as a main
      transition between the lamellar gel (L(beta)) and liquid-crystalline (L(alpha))
      phases on the basis of the values of enthalpy change (DeltaH) and slope of the
      transition temperature with respect to pressure (dT/dP). The DSC thermogram of
      the OMPC bilayer membrane similarly showed a single endothermic peak but two
      kinds of phase transitions were observed at different temperatures in the light
      transmittance profile at high pressures. The extrapolation of the lower
      temperature transition in the high-pressure range to an ambient pressure
      coincided with the transition observed in the DSC thermogram. This transition was
      identified as a transition between the lamellar crystal (L(c)) and L(alpha) (or
      L(beta)) phases from the DeltaH and dT/dP values. The higher-temperature
      transition, appearing only at high pressures, was identified as the
      L(beta)/L(alpha) transition considering the topological resemblance of its
      temperature-pressure phase diagram as that of the dioleoylphosphatidylcholine
      bilayer membrane. The phase diagram of the OMPC bilayer membrane demonstrated
      that the L(beta) phase cannot exist at pressures below ca. 190 MPa while it can
      exist stably in a finite temperature range at pressures above the pressure.

PMID- 18804321
TI  - Evaluation of alternative approaches for screening contaminated sediments and
      soils for polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans.
AB  - Traditional high resolution mass spectrometry (HRMS) analysis for polychlorinated
      dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/Fs) can be time
      consuming and expensive. Consequently, alternative methods are of great interest
      to regulatory agencies and others characterizing contaminated sites. One factor
      that hinders acceptance of alternative methods is a lack of performance
      information that assesses the alternative method's impacts on analytical results.
      The U.S. Environmental Protection Agency's Superfund Innovative Technology
      Evaluation Monitoring and Measurement Technologies Program (EPA SITE MMT)
      encourages the development and implementation of innovative and alternative
      monitoring methods by providing performance information on site characterization
      technologies. This paper presents a comparison of the results obtained from
      laboratory-based alternative approaches for screening sediment and soil samples
      for dioxin toxicity equivalents (TEQ(D/F)) to results obtained using traditional
      HRMS. The laboratory-based approaches included modifying the traditional HRMS
      analysis to make it more cost-effective (alternate 1613B), analyzing extracts
      that had been prepared for HRMS using low resolution mass spectrometry, and
      determining total organic carbon (TOC) content as an indicator of PCDD/F content.
      These comparisons demonstrated that TEQ(D/F) values generated using toxicity
      equivalency factors proposed by the World Health Organization in 1998 applied to
      alternate 1613B and LRMS analyses have a strong linear correlation to the
      TEQ(D/F) values derived in the same fashion from traditional HRMS analysis. These
      results would have placed >90% of the samples within the same concentration
      intervals using ranges of <0.05, 0.05-0.50, 0.50-5, and >5ng TEQ/g. Natural log
      transformed data for TOC had significantly weaker correlation to TEQ(D/F),
      indicating that TOC is not a reliable indicator of TEQ(D/F) concentrations.

PMID- 18804322
TI  - Managing the intractable: communicative structures for management of
      hexachlorobenzene and other scheduled wastes.
AB  - This paper explores issues of governance and decision-making structures
      associated with the problem of hexachlorobenzene (HCB) waste at Botany in New
      South Wales. From a government perspective, the problem is 'downstream' of a well
      known national controversy over whether Australia should have a high-temperature
      incinerator (HTI) to 'dispose' of such scheduled wastes. The 1992 decision not to
      proceed with HTI followed an extensive process of public consultation, which,
      against the expectations of industry and government, saw the emergence of
      Australia-wide community opposition. Alternative national management plans were
      formulated for the treatment of several types of organochlorine waste, with the
      scheme of these plans first approved in 1993 by the Australian and New Zealand
      Environment and Conservation Council (ANZECC). The HCB Management Plan is one of
      three such plans (the others being for PCBs and organochlorine pesticides). With
      this, ANZECC established the Scheduled Waste Management Group comprising
      government officials, and the National Advisory Body (NAB) made up of
      stakeholders. Officially the NAB had oversight of the HCB problem until 2002 when
      it was disbanded. As a result of the HTI experience, new community consultation
      protocols were introduced in association with the alternative management plans.
      For HCBs, which are confined almost entirely to Orica's Botany site in
      southeastern Sydney, this led to the establishment of the Community Participation
      and Review Committee (CPRC), a representative body with review and advisory
      functions. This paper draws conclusions from this history about government
      processes of decision making, the role of individual and institutional actors,
      the central importance of trust, and the democratisation of risk management.
      Using concepts delineated by McDonell [1991. Toxic waste management in Australia:
      why did policy reform fail? Environment 33(6), 11-13, 33-39; 1997. Scientific and
      everyday knowledge: trust and the politics of environmental initiatives. Social
      Studies of Science 27, 819-863.] we identify swings towards, then away from
      institutionalised trust. Across two decades, government and industry have placed
      faith in centrally controlled mechanisms for public participation, hoping to
      garner trust and legitimate privileged technological solutions. On the
      'backswings', these processes have seen public trust dissipate in the face of
      government misunderstanding of the opportunities for effective bureaucratic
      interventions.

PMID- 18804323
TI  - When unequals are treated equally: the 2002 commission of inquiry into Orica's
      Geomelt proposal.
AB  - This paper deals with the Commission of Inquiry (COI) established by the NSW
      Department of Planning to examine Orica's proposal to build a Geomelt plant at
      its Botany site to destroy its stockpile of Hexachlorobenzene. The Inquiry is
      analysed in light of the literature on democracy/democratisation. The paper
      argues that the standard operating procedures of the Inquiry ensured that all
      stakeholders were treated equally. However, this equality was found to be purely
      formal, and drawing on the critique of formal equality dating back to Aristotle,
      it is argued that treating unequals equally results in the circumvention of
      deliberative democratic ideals by perpetuating entrenched structural inequalities
      while nonetheless giving the superficial appearance of fair play.

PMID- 18804324
TI  - Assessing the value of information for water quality management in the North Sea.
AB  - Global Earth Observation (GEO) is one of the most important sources of
      information for environmental resource management and disaster prevention. With
      budgets for GEO increasingly under pressure, it is becoming important to be able
      to quantify the returns to informational investments. For this, a clear
      analytical framework is lacking. By combining Bayesian decision theory with an
      empirical, stakeholder-oriented approach, this paper attempts to develop such a
      framework. The analysis focuses on the use of satellite observations for Dutch
      water quality management in the North Sea. Dutch water quality management
      currently relies on information from 'in situ' measurements but is considering
      extending and deepening its information base with satellite observations. To
      estimate returns to additional investments in satellite observation, we analyze
      the added value of an extended monitoring system for the management of
      eutrophication, potentially harmful algal blooms and suspended sediment and
      turbidity in the North Sea. First, we develop a model to make the potential
      contribution of information to welfare explicit. Second, we use this model to
      develop a questionnaire and interpret the results. The results indicate that the
      expected welfare impact of investing in satellite observation is positive, but
      that outcomes strongly depend on the accuracy of the information system and the
      range of informational benefits perceived.

PMID- 18804325
TI  - Collaborative GIS for spatial decision support and visualization.

PMID- 18804326
TI  - Jute stick powder as a potential biomass for the removal of congo red and
      rhodamine B from their aqueous solution.
AB  - Jute stick powder (JSP) has been found to be a promising material for adsorptive
      removal of congo red (C.I. 22120) and rhodamine B (C.I. 45170) from aqueous
      solutions. Physico-chemical parameters like dye concentration, solution pH,
      temperature and contact time have been varied to study the adsorption phenomenon.
      Favorable adsorption occurs at around pH 7.0 whereas temperature has no
      significant effect on adsorption of both the dyes. The maximum adsorption
      capacity has been calculated to be 35.7 and 87.7mg/g of the biomass for congo red
      and rhodamine B, respectively. The adsorption process is in conformity with
      Freundlich and Langmuir isotherms for rhodamine B whereas congo red adsorption
      fits well to Langmuir isotherm only. In both the cases, adsorption occurs very
      fast initially and attains equilibrium within 60min. Kinetic results suggest the
      intra-particle diffusion of dyes as rate limiting step.

PMID- 18804327
TI  - Removal of Acid Orange 7 from water by electrochemically generated Fenton's
      reagent.
AB  - The removal of azo dye Acid Orange 7 (AO7) from water was investigated by the
      electro-Fenton technology using electrogenerated hydroxyl radicals (OH) which
      leads to the oxidative degradation of AO7 up to its complete mineralization.
      H(2)O(2) and Fe (II) ions are electrogenerated in a catalytic way at the carbon
      felt cathode. AO7 decay kinetics and evolution of its oxidation intermediates
      were monitored by high-performance liquid chromatography. The absolute rate
      constant of AO7 hydroxylation reaction has been determined as (1.20+/
      0.17)x10(10)M(-1)s(-1). The optimal current value for the degradation of AO7 was
      found as 300 mA. AO7 degradation rate was found to decrease by increase in Fe(3+)
      concentration beyond 0.1mM. Mineralization of AO7 aqueous solutions was followed
      by total organic carbon (TOC) measurements and found to be 92%. Based on TOC
      evolution and identification of aromatic intermediates, short-chain carboxylic
      acids and inorganic ions released during treatment, a plausible mineralization
      pathway was proposed.

PMID- 18804328
TI  - Kinetics of transformation of 1,1,1-trichloroethane by Fe(II) in cement slurries.
AB  - This study examines the applicability of the iron-based degradative
      solidification/stabilization (DS/S-Fe(II)) process to 1,1,1-trichloroethane
      (1,1,1-TCA), which is one of common chlorinated aliphatic hydrocarbons (CAHs) of
      concern at contaminated sites. DS/S-Fe(II) combines contaminant degradation by
      Fe(II) and immobilization by the hydration reactions of Portland cement. The
      transformation of 1,1,1-TCA by Fe(II) in 10% Portland cement slurries was studied
      using a batch slurry reactor system. The effects of Fe(II) dose, pH, and initial
      concentration of 1,1,1-TCA on the kinetics of 1,1,1-TCA degradation were
      evaluated. Degradation of 1,1,1-TCA in cement slurries including Fe(II) was very
      rapid and could be described by a pseudo-first-order rate law. The half-lives for
      1,1,1-TCA were measured between 0.4 and 5h when Fe(II) dose ranged from 4.9 to
      39.2mM. The pseudo-first-order rate constant increased with pH to a maximum near
      pH 12.5. A saturation rate equation was able to predict degradation kinetics over
      a wide range of target organic concentrations and at higher Fe(II) doses. The
      major transformation product of 1,1,1-TCA in mixtures of Fe(II) and cement was
      1,1-dichloroethane (1,1-DCA), which indicates that degradation occurred by a
      hydrogenolysis pathway. A small amount of ethane was observed. The conversion of
      1,1,1-TCA to ethane was better described by a parallel reaction model than by a
      consecutive reaction model.

PMID- 18804329
TI  - Genetic diversity of Toxoplasma gondii isolates from chickens from Brazil.
AB  - Until recently, Toxoplasma gondii was considered clonal with very little genetic
      variability. Recent studies indicate that T. gondii isolates from Brazil are
      genetically and biologically different from T. gondii isolates from USA and
      Europe. In the present study, we retyped 151 free range chicken isolates from
      Brazil including 117 newly isolated samples from 11 geographically areas
      (Alagoas, Bahia, Ceara, Maranhao, Parana, Pernambuco, Rio de Janeiro, Rio Grande
      do Norte, Sao Paulo, Sergipe, and Rondonia) and 34 previously reported isolates
      from the very north (Para) and the very south (Rio Grande do Sul). Ten PCR-RFLP
      markers including SAG1, SAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1, and
      Apico were used to genotype all isolates. Overall analysis of 151 T. gondii
      isolates revealed 58 genotypes. Half (29/58) of these genotypes had single
      isolate and the other half of the genotypes were characterized with two or more
      isolates. Only 1 of 151 isolates was clonal Type I strain and 5 were clonal Type
      III strains. Two isolates had mixed infections. Clonal Type II strain was absent.
      One strain was Type II at all loci, except BTUB. The results confirm high genetic
      diversity of T. gondii isolates from Brazil.

PMID- 18804330
TI  - Intranasal insulin attenuates the hypothalamic-pituitary-adrenal axis response to
      psychosocial stress.
AB  - Previous studies have shown that intranasally administered insulin exerts an
      inhibitory influence on the basal hypothalamic-pituitary-adrenal (HPA) axis
      activity. To date, however, it remains unclear as to whether intranasal insulin
      does furthermore affect HPA axis responsiveness in situations of stress. Here, we
      tested whether intranasally administered insulin attenuates the HPA axis response
      to psychosocial stress. Fifty minutes before being exposed to the Trier Social
      Stress Test (TSST), 26 healthy young male participants received a single
      intranasal dose of human insulin (40 I.U.) or placebo in a placebo controlled,
      double-blind between-subject design. Plasma cortisol, saliva cortisol, heart
      rate, and blood pressure were measured at resting baseline and in response to the
      TSST. Plasma cortisol (P<.001) and saliva cortisol (P<.001) increased in response
      to stress, as did heart rate (P<.001) and blood pressure (P<.001). Intranasal
      insulin did not influence plasma or saliva cortisol, heart rate, blood pressure,
      blood glucose, and plasma insulin levels at baseline. However, intranasal insulin
      diminished the saliva cortisol (two-way ANOVA; treatment by time interaction:
      P=.05) and plasma cortisol (two-way ANOVA; treatment by time interaction: P=.05)
      response to the TSST without affecting heart rate, and blood pressure stress
      reactivity. Our data show that a single intranasal insulin administration
      effectively lowers stress-induced HPA axis responsiveness. Intranasal insulin may
      offer a therapeutic potential to prevent hyperactivity of the HPA system.

PMID- 18804331
TI  - Smoking cessation and relapse prevention for postpartum women: results from a
      randomized controlled trial at 6, 12, 18 and 24 months.
AB  - AIM: To test the efficacy of an aid to cessation/relapse prevention intervention
      for women postpartum. METHOD: Two-armed randomized controlled trial. Follow-ups
      at 6, 12, 18, and 24 months, screenings on maternity wards. Intervention group
      received face-to-face counseling 40 days postpartum plus telephone counseling
      calls 4 and 12 weeks later. Control group received usual care plus self-help
      material for each parent. RESULTS: With regard to smoking cessation, 4 week point
      prevalence abstinent rates were higher in the treatment group at 6, 12, and 18
      months (7% vs. 1%, 7% vs. 2%, and 9% vs. 1%, respectively). Sustained abstinence
      was higher in the treatment group at 6 months follow-up (3% vs. 0%). No
      difference was observed with regard to relapse prevention. DISCUSSION: Regarding
      aid to cessation we observed small effects, regarding relapse prevention no
      effect. In order to capitalize on the opportunity childbirth poses with regard to
      smoking, theories on relapse prevention in smoking cessation that guide in
      designing interventions are needed.

PMID- 18804332
TI  - Auditory hallucinations in schizophrenia - outcry of a diseased brain?
AB  - Schizophrenia, with a lifetime prevalence of one percent, is one of the most
      common mental diseases. Regarding the typology and definition, hallucinations of
      different qualities (auditory, visual, tactile, olfactory and gustatory)
      represent a so-called core symptom according to the modern classification systems
      ICD-10 and DSM-IV. However, under functional imaging evaluation (MEG) of a
      neuronal correlate of the disease, truly asymmetric relationships were found.
      While the notable neurophysiological finding was a general slowing of delta-theta
      activity within the temporal lobe, an increase in beta activity was found within
      the same zone during auditory hallucinations, which raises the question of
      whether this might be an intermittent compensation mechanism of the brain, also
      in the sense of a self-healing function. This might lead one to speculate whether
      the supposed core symptom of the disease, auditory hallucination, is not in fact
      a possible resistance mechanism. If this hypothesis blurts out any measure of
      truth, the usual therapeutic algorithm will have to be re-evaluated.

PMID- 18804333
TI  - Automatic segmentation of whole breast using atlas approach and deformable image
      registration.
AB  - PURPOSE: To compare interobserver variations in delineating the whole breast for
      treatment planning using two contouring methods. METHODS AND MATERIALS:
      Autosegmented contours were generated by a deformable image registration-based
      breast segmentation method (DEF-SEG) by mapping the whole breast clinical target
      volume (CTVwb) from a template case to a new patient case. Eight breast radiation
      oncologists modified the autosegmented contours as necessary to achieve a
      clinically appropriate CTVwb and then recontoured the same case from scratch for
      comparison. The times to complete each approach, as well as the interobserver
      variations, were analyzed. The template case was also mapped to 10 breast cancer
      patients with a body mass index of 19.1-35.9 kg/m(2). The three-dimensional
      surface-to-surface distances and volume overlapping analyses were computed to
      quantify contour variations. RESULTS: The median time to edit the DEF-SEG
      generated CTVwb was 12.9 min (range, 3.4-35.9) compared with 18.6 min (range, 8.9
      45.2) to contour the CTVwb from scratch (30% faster, p = 0.028). The mean surface
      to-surface distance was noticeably reduced from 1.6 mm among the contours
      generated from scratch to 1.0 mm using the DEF-SEG method (p = 0.047). The
      deformed contours in 10 patients achieved 94% volume overlap before correction
      and required editing of 5% (range, 1-10%) of the contoured volume. CONCLUSION:
      Significant interobserver variations suggested a lack of consensus regarding the
      CTVwb, even among breast cancer specialists. Using the DEF-SEG method produced
      more consistent results and required less time. The DEF-SEG method can be
      successfully applied to patients with different body mass indexes.

PMID- 18804334
TI  - Quality of radiotherapy reporting in randomized controlled trials of Hodgkin's
      lymphoma and non-Hodgkin's lymphoma: a systematic review.
AB  - PURPOSE: Standards for the reporting of radiotherapy details in randomized
      controlled trials (RCTs) are lacking. Although radiotherapy (RT) is an important
      component of curative therapy for Hodgkin's lymphoma (HL) and non-Hodgkin's
      lymphoma (NHL), we postulated that RT reporting may be inadequate in Phase III HL
      and NHL trials. METHODS AND MATERIALS: We searched PubMed and the Cochrane
      registry for reports of RCTs involving RT and either HL or NHL published between
      1998 and 2007. We screened 133 titles and abstracts to identify relevant studies.
      We included a total of 61 reports. We assessed these reports for the presence of
      six quality measures: target volume, radiation dose, fractionation, radiation
      prescription, quality assurance (QA) process use, and adherence to QA (i.e.,
      reporting of major or minor deviations). RESULTS: Of 61 reports, 23 (38%)
      described the target volume. Of the 42 reports involving involved-field RT alone,
      only 8 (19%) adequately described the target volume. The radiation dose and
      fractionation was described in most reports (54 reports [89%] and 39 reports
      [64%], respectively). Thirteen reports specified the RT prescription point (21%).
      Only 12 reports (20%) described using a RT QA process, and 7 reports (11%)
      described adherence to the QA process. CONCLUSION: Reporting of RT in HL and NHL
      RCTs is deficient. Because the interpretation, replication, and application of
      RCT results depend on adequate description and QA of therapeutic interventions,
      consensus standards for RT reporting should be developed and integrated into the
      peer-review process.

PMID- 18804335
TI  - Comparison of spine, carina, and tumor as registration landmarks for volumetric
      image-guided lung radiotherapy.
AB  - PURPOSE: To assess the feasibility, reproducibility, and accuracy of volumetric
      lung image guidance using different thoracic landmarks for image registration.
      METHODS AND MATERIALS: In 30 lung patients, four independent observers conducted
      automated and manual image registrations on Day 1 cone-beam computed tomography
      data sets using the spine, carina, and tumor (720 image registrations). The image
      registration was timed, and the couch displacements were recorded. The intraclass
      correlation was used to assess reproducibility, and the Bland-Altman analysis was
      used to compare the automatic and manual matching methods. Tumor coverage
      (accuracy) was assessed through grading the tumor position after image matching
      against the internal target volume and planning target volume. RESULTS: The image
      guided process took an average of 1 min for all techniques, with the exception of
      manual tumor matching, which took 4 min. Reproducibility was greatest for
      automatic carina matching (intraclass correlation, 0.90-0.93) and lowest for
      manual tumor matching (intraclass correlation, 0.07-0.43) in the left-right,
      superoinferior, and anteroposterior directions, respectively. The Bland-Altman
      analysis showed no significant difference between the automatic and manual
      registration methods. The tumor was within the internal target volume 62% and 60%
      of the time and was outside the internal target volume, but within the planning
      target volume, 38% and 40% of the time after automatic spine and automatic carina
      matching, respectively. CONCLUSION: For advanced lung cancer, the spine or carina
      can be used equally for cone-beam computed tomography image registration without
      compromising target coverage. The carina was more reproducible than the spine,
      but additional analysis is required to confirm its validation as a tumor
      surrogate. Soft-tissue registration is unsuitable at present, given the
      limitations in contrast resolution and the high interobserver variability.

PMID- 18804336
TI  - Factors affecting the efficiency of producing porcine embryos expressing enhanced
      green fluorescence protein by ICSI-mediated gene transfer method.
AB  - This study aims to investigate factors that affect the efficiency of blastocyst
      development and enhanced green fluorescence protein (EGFP) expression in porcine
      embryos following intracytoplasmic sperm injection (ICSI)-mediated DNA transfer.
      Frozen-thawed dead spermatozoa were exposed to different concentrations (0.01
      microg/mL, 0.05 microg/mL or 0.1 microg/mL) of EGFP DNA solution, and then
      microinjected into in vitro matured oocytes. The optimal concentration for EGFP
      expression of resultant embryos was 0.05 microg/mL. When oocytes were
      microinjected on a warm stage at 30 degrees C, the percentage of EGFP-expressing
      embryos was higher than that at 38.5 degrees C (40.1% vs. 20.9%, P<0.01). The
      efficiency of EGFP expression in embryos following ICSI using linear EGFP DNA
      exposed spermatozoa was higher than using circular DNA (40.8% vs. 28.2%, P<0.05).
      ICSI oocytes treated with 6-DMAP after electro-activation had a higher percentage
      of embryos expressing EGFP than those not treated (52.5% vs. 26.3%, P<0.01).
      However, neither incubation temperatures of spermatozoa and DNA (4 degrees C, 24
      degrees C or 39 degrees C) nor BSA addition to the incubation medium affected the
      efficiency of producing EGFP-expressing embryos. Furthermore, treatment with
      DNase I after preincubation of sperm and DNA prevented the embryos from
      expressing EGFP. The EGFP expression of ICSI oocytes was affected neither by
      intracytoplasmic injection using sperm heads or whole spermatozoa, nor by washing
      of the sperm after preincubation. The above-mentioned factors did not affect
      embryonic developmental competence, apart from 6-DMAP treatment after electro
      activation. In conclusion, most exogenous DNA molecules were tightly bound on the
      membranes of sperm head after incubation of DNA and sperm, and the temperature
      during ICSI, 6-DMAP treatment, exogenous DNA concentrations and constructs could
      significantly affect EGFP expression in porcine embryos following ICSI-mediated
      DNA transfer.

PMID- 18804337
TI  - Polymorphisms of the endothelial nitric oxide synthase gene in premenopausal
      women with polycystic ovary syndrome.
AB  - OBJECTIVES: To investigate the association of two common genetic polymorphisms of
      the gene encoding for endothelial nitric oxide synthase (Nos3), the enzyme
      catalyzing the production of nitric oxide (NO), with occurrence of the polycystic
      ovary syndrome (PCOS). METHODS: In a prospective case-control study, we analyzed
      2 polymorphisms of the Nos3 gene cluster (Nos 3 exon 7 Glu298Asp and 27-base pair
      repeat in intron 4 of Nos3) in a series of 210 premenopausal Caucasian women with
      PCOS and 171 healthy controls using pyrosequencing and PCR, respectively. Women
      completed a detailed questionnaire and underwent a peripheral venous puncture,
      ultrasonography, and a standardized oral glucose tolerance test (OGTT). RESULTS:
      Genotype frequencies were not significantly different among women with PCOS and
      controls for the exon 7Nos3 and the intron 4Nos3 polymorphism (p=0.3 and 0.2,
      respectively). CONCLUSIONS: In our series, two common polymorphisms of the Nos3
      gene cluster were not associated with occurrence of PCOS.

PMID- 18804338
TI  - Quality of potent Mn porphyrin-based SOD mimics and peroxynitrite scavengers for
      pre-clinical mechanistic/therapeutic purposes.
AB  - Cationic Mn porphyrins are among the most potent SOD mimics and peroxynitrite
      scavengers. They have been widely and successfully used in different models of
      oxidative stress and are either progressing towards or are in phase I of clinical
      trials. The most frequently used compounds are Mn(III) meso-tetrakis(N
      ethylpyridinium-2-yl)porphyrin (MnTE-2-PyP(5+) or AEOL10113), its methyl analogue
      (MnTM-2-PyP(5+) or AEOL10112), and Mn(III) meso-tetrakis(4-benzoic acid)porphyrin
      (MnTBAP). A great discrepancy between the in vivo data obtained with Calbiochem
      preparations and those of authentic MnTE-2-PyP(5+) and MnTM-2-PyP(5+) samples
      were recently observed. Surprisingly, the commercial samples were invariably of
      poor identity and consisted of mixtures of nearly equal contributions of non
      alkylated, mono-, di-, tri- and tetraalkylated porphyrins, lacking thus the major
      structural entity that determines their antioxidant potency, i.e., the four
      positively charged orthoN-alkylpyridyl groups that afford thermodynamic tuning of
      the active site and electrostatic guidance of anionic superoxide and
      peroxynitrite species toward the metal center. The MnTE-2-PyP(5+) and MnTM-2
      PyP(5+) compounds were not even the major species in the commercial samples sold
      as "MnTE-2-PyP" and "MnTM-2-PyP", respectively. While we have already reported
      the insufficient impurity of the MnTBAP samples from Alexis and other suppliers,
      in one more recent lot the situation is dramatic, as 25% of the sample was not
      MnTBAP, but metal-free ligand, H(2)TBAP. The (unintentional) use of the Mn
      porphyrins of low quality compromises therapeutic and/or mechanistic conclusions.
      Simple techniques, which include thin-layer chromatography, electrospray-mass
      spectrometry, UV-vis spectroscopy, and electrochemistry described here could be
      used routinely to check the overall quality of Mn porphyrins in order to avoid
      misleading conclusions and waste of valuable resources (animals, compounds, time,
      manpower).

PMID- 18804339
TI  - TLR4-mediated MyD88-dependent signaling pathway is activated by cerebral ischemia
      reperfusion in cortex in mice.
AB  - To study whether the signaling pathway is activated in the inflammatory reaction
      of cerebral ischemia-reperfusion and its mechanism. The mice were randomly
      divided into sham group, ischemia-reperfusion group and TLR4-blocked group with
      different time points of reperfusion 12h, 24h, 48h and 72h group. We observed the
      different expression of TLR4 mRNA and MyD88 mRNA, activation of NF-kappaB and the
      TNF-alpha and IL-1beta protein levels in each group at different time point after
      ischemia-reperfusion. Mice cerebral ischemia was induced by occlusion of common
      carotid arteries (CCA) bilaterally. TLR4 signaling pathway could be inhibited by
      specific anti-TLR4 binding protein to prevent TLR4 from interacting with its
      receptors. We determined the result of TLR4 antibodies-blocking and mice cerebral
      ischemia-reperfusion injuries by Western blot, and evaluated neuronal damage in
      cortex. We also determined the expression of TLR4 mRNA and MyD88 mRNA by in situ
      hybridization (ISH), the activation of NF-kappaB by EMSA, and the expression of
      TNF-alpha protein by Western blot. Anti-TLR4 binding TLR4 receptors before
      reperfusion was effective; There was distinct difference among each group
      respecting neuronal damage; The expression of TLR4 mRNA and MyD88 mRNA, the
      activation of NF-kappaB, and the expression of TNF-alpha protein showed clear
      difference as well. LR4-mediated MyD88-dependent signaling pathway activated by
      ischemia-reperfusion may be involved in the mechanism of ischemia-reperfusion
      through upregulation of NF-kappaB and TNF-alpha.

PMID- 18804340
TI  - Implication of intracellular ROS formation, caspase-3 activation and Egr-1
      induction in platycodon D-induced apoptosis of U937 human leukemia cells.
AB  - Platycodon D is a major constituent of triterpene saponins found in the root of
      Platycodon grandiflorum, Platycodi Radix, which is widely used in traditional
      Oriental medicine for the treatment of many chronic inflammatory diseases. The
      results of previous studies have shown that this compound has in vitro growth
      inhibitory activity in human cancer cells, however, the mechanism by which this
      action occurs is poorly understood. In this study, we examined the effects of
      platycodon D on the production of reactive oxygen species (ROS) and evaluated the
      association of these effects with apoptotic tumor cell death using a human
      leukemic U937 cell line. The results of this study demonstrate that platycodon D
      mediates ROS production, and that this mediation is followed by a decrease in
      mitochondrial membrane potential (MMP, DJm), activation of caspase-3, and
      cleavage of poly (ADP-ribose) polymerase (PARP). Both the cytotoxic effects and
      apoptotic characteristics induced by platycodon D treatment were significantly
      inhibited by z-DEVD-fmk, a caspase-3 inhibitor, which demonstrates the important
      role that caspase-3 plays in the observed cytotoxic effect. Additionally, the
      transcription factor early growth response-1 (Egr-1) gene was transcriptionally
      activated and the levels of non-steroidal anti-inflammatory drug (NSAID)
      activated gene-1 (NAG-1) protein were elevated in platycodon D-treatedU937 cells.
      However, the quenching of ROS generation in response to treatment with a ROS
      scavenger, N-acetyl-L-cysteine, reversed the platycodon D-induced apoptosis
      effects via inhibition of Egr-1 activation, ROS production, MMP collapse, and the
      subsequent activation of caspase-3. Although further studies are needed to
      demonstrate that increased expression of Egr-1 by platycodon D leads directly to
      NAG-1 induction and subsequent apoptosis, our observations clearly indicate that
      ROS induced through Egr-1 activation are involved in the early molecular events
      involved in the platycodon D-induced apoptotic pathway.

PMID- 18804341
TI  - [Skin cancers: do not underestimate the risks].

PMID- 18804342
TI  - THAM improves an experimentally induced severe dyspnea.
AB  - Inhibition of ventilatory drive may improve the sensation of dyspnea, because
      heightened ventilatory demand contributes to dyspnea. Tris-hydroxymethyl
      aminomethane (THAM) is an alkalizing agent that does not increase CO(2)
      production and exerts a depressant effect on respiration. The purpose of this
      study was to clarify the effect of THAM on dyspnea associated with increases in
      respiratory drive. We investigated the effects of THAM on dyspneic sensation
      produced by a combination of hypercapnia (mean PaCO(2)=52 mm Hg) and elastic
      loading (30 cm H(2)O/L) in 14 healthy subjects. The subjects were asked to rate
      their dyspneic sensation using a visual analogue scale (VAS) during the loaded
      breathing while monitoring ventilation using a pneumotachograph. THAM was infused
      at a rate of 0.4 mL/kg/minute for 10 minutes, and the effects of THAM on dyspnea
      and ventilation were evaluated by comparing the steady-state values of
      ventilatory variables and VAS score obtained before and after THAM
      administration. Administration of THAM corrected respiratory acidosis and was
      associated with significant improvements in VAS score and significant decreases
      in minute ventilation, respiratory frequency, and ventilatory drive. THAM
      administration greatly alleviates dyspneic sensation associated with the increase
      in respiratory drive and could be an effective therapy for treating severe
      dyspnea in patients with hypercapnia.

PMID- 18804343
TI  - Influence of the tooth section technique in alveolar nerve damage after surgery
      of impacted lower third molars.
AB  - This study is a randomized control split-mouth non-blinded prospective trial, the
      aim of which was to evaluate clinically the frequency and type of injury to the
      inferior alveolar nerve (IAN) following mandibular third molar surgery using or
      not using the tooth section technique. The sample consisted of 50 lower third
      molars in 25 patients, in the control group the tooth section technique was not
      used, and it was used in the experimental group. The outcomes have shown a
      frequency of 8% of IAN injury for both groups (in both genders), and there were
      no statistically significant associations between the use of the tooth section
      technique and a diminished incidence of IAN injury or the presence of
      radiographic signs of a direct relationship between the tooth/nerve/mandibular
      canal and IAN injury. There was no association between deformities of the tip of
      dental needles and nerve injury. Temporary hypoesthesia and paresthesia were the
      commonest nerve injuries. All patients recovered from these injuries within six
      months.

PMID- 18804344
TI  - Ketamine successfully terminates malignant status epilepticus.
AB  - A 22-year-old woman with mitochondriopathy and pre-existing epilepsy developed
      status epilepticus (SE) not responding to benzodiazepines, phenytoin, thiopental,
      and propofol. SE was terminated within days after supplemental administration of
      continuous ketamine infusion to midazolam. The case suggests strong
      anticonvulsant properties of ketamine even after failure of GABAergic
      anesthetics, likely due to increased NMDA receptor expression with ongoing
      seizure activity. Thus, ketamine should be incorporated into therapeutic regimens
      for difficult-to-treat SE.

PMID- 18804345
TI  - Geographic variation and sociodemographic characteristics of psychotic disorders
      in Finland.
AB  - BACKGROUND: Geographical variation and sociodemographic characteristics may
      differ in affective and nonaffective psychotic disorders. We examined the
      geographical variation in the lifetime prevalence of psychotic disorders in a
      comprehensive general population study. METHOD: A nationally representative
      sample of 8028 Finns aged 30 or over was screened for psychotic and bipolar I
      disorders and interviewed with the Structured Clinical Interview for DSM-IV. Best
      estimate DSM-IV diagnoses were formed by combining interview and case note data.
      Nationwide health care register data were used for the nonrespondents.
      Associations with sociodemographic features, place of birth and residence in
      urban or rural areas and in five regions, and migration between the regions were
      examined. RESULTS: Schizophrenia and other nonaffective psychoses, but not
      affective psychoses, showed prominent regional variation, with highest odds found
      for schizophrenia among those born in the North (OR 7.72 95%CI 2.48-24.04) and
      the East (OR 3.99 95%CI 1.22-13.11). The risk of any psychotic disorder was lower
      for those born in urban areas (OR 0.73 95%CI 0.54-0.98), but no associations were
      found for separate diagnostic groups. Region of birth was the strongest
      determinant of geographical variation when both place of birth and residence were
      accounted for. Selective migration was not found. Education and income were
      higher and being employed more common in subjects with affective psychosis than
      in subjects with other psychotic disorders. CONCLUSIONS: Large area variation is
      more important than urban-rural disparity in psychotic disorders in Finland.
      Affective psychoses were different from nonaffective psychoses in terms of both
      regional variation and sociodemographic features.

PMID- 18804347
TI  - Pentoxifylline inhibits replication of Japanese encephalitis virus: a comparative
      study with ribavirin.
AB  - Several investigations have shown that pentoxifylline possesses broad-spectrum
      antiviral activity against a range of RNA and DNA viruses. However, its ability
      to inhibit Japanese encephalitis virus (JEV) replication has not yet been
      studied. The present study was designed to investigate the antiviral activity of
      pentoxifylline against JEV in vitro and in vivo. The activity of pentoxifylline
      against JEV was evaluated in vitro using cytopathic effect inhibition and plaque
      reduction assays. Pentoxifylline was able to inhibit JEV replication in a dose
      dependent manner at a 50% inhibitory concentration (IC(50)) of 50.3microg/mL
      (0.00018microM) and a therapeutic index (TI) of 10. Experiments to study the
      mechanism of antiviral action of pentoxifylline using in vitro translation of
      viral mRNA suggested that the drug did not interfere either with early or late
      protein synthesis but most likely exerted its action on virus assembly and/or
      release. Furthermore, the in vivo study showed that pentoxifylline at a
      concentration of 100mg/kg and 200mg/kg body weight was able to protect completely
      mice challenged with 50 x 50% lethal dose (LD(50)) of JEV.

PMID- 18804346
TI  - Interaction between interleukin 3 and dystrobrevin-binding protein 1 in
      schizophrenia.
AB  - Schizophrenia is a common psychotic mental disorder that is believed to result
      from the effects of multiple genetic and environmental factors. In this study, we
      explored gene-gene interactions and main effects in both case-control (657 cases
      and 411 controls) and family-based (273 families, 1,350 subjects) datasets of
      English or Irish ancestry. Fifty three markers in 8 genes were genotyped in the
      family sample and 44 markers in 7 genes were genotyped in the case-control
      sample. The Multifactor Dimensionality Reduction Pedigree Disequilibrium Test
      (MDR-PDT) was used to examine epistasis in the family dataset and a 3-locus model
      was identified (permuted p=0.003). The 3-locus model involved the IL3
      (rs2069803), RGS4 (rs2661319), and DTNBP1 (rs2619539) genes. We used MDR to
      analyze the case-control dataset containing the same markers typed in the RGS4,
      IL3 and DTNBP1 genes and found evidence of a joint effect between IL3 (rs31400)
      and DTNBP1 (rs760761) (cross-validation consistency 4/5, balanced prediction
      accuracy=56.84%, p=0.019). While this is not a direct replication, the results
      obtained from both the family and case-control samples collectively suggest that
      IL3 and DTNBP1 are likely to interact and jointly contribute to increase risk for
      schizophrenia. We also observed a significant main effect in DTNBP1, which
      survived correction for multiple comparisons, and numerous nominally significant
      effects in several genes.

PMID- 18804348
TI  - In vivo efficacy of humanised intermittent versus continuous ceftazidime in
      combination with tobramycin in an experimental model of pseudomonal pneumonia.
AB  - In this study, we compared the efficacy of ceftazidime (CAZ) intermittent versus
      continuous infusion with or without tobramycin (TOB) for the treatment of
      pneumonia caused by Pseudomonas aeruginosa in rabbits. Treatments were humanised
      and mimicked intermittent CAZ (iCAZ) (2g three times daily), continuous CAZ
      (cCAZ) (4g once daily (qd)) and TOB (10mg/kg qd). Minimum inhibitory
      concentrations (MICs) were 1mg/L and 4mg/L for TOB and CAZ, respectively.
      Bacterial efficacy in lungs was as follows: control, 9+/-0.6 colony-forming units
      (CFU)/g; TOB monotherapy, 8+/-0.5CFU/g; iCAZ monotherapy, 7.8+/-1.4CFU/g; cCAZ
      monotherapy, 8+/-0.4CFU/g (P = 0.005); and iCAZ+TOB, 8+/-0.5CFU/g; cCAZ+TOB,
      7.2+/-0.3CFU/g (P < 0.05). Bacterial efficacy in the spleen was as follows (%
      sterile): control, 4+/-1.6CFU/g (0%); TOB monotherapy, 1.7+/-1.2CFU/g (60%); iCAZ
      monotherapy, 3.5+/-0.5CFU/g (17%); cCAZ monotherapy, 1.5+/-0.6CFU/g (75%) (P =
      0.02); and iCAZ+TOB, 2.1+/-0.6CFU/g (50%); cCAZ+TOB, 1.2+/-0.3CFU/g (82%) (P <
      0.05). The time the drug concentration was above the MIC (T > MIC) was 62% and
      99% for iCAZ and cCAZ, respectively. We conclude that CAZ is more effective when
      administered continuously, especially for the sterilisation of septicaemia. A
      synergistic therapeutic effect of the association CAZ+TOB was observed in vivo,
      which can be explained by the longer T > MIC of cCAZ. These findings suggest that
      continuous treatment with 4g CAZ could be appropriate in patients with P.
      aeruginosa infections.

PMID- 18804349
TI  - Penicillin-resistant viridans group streptococci from blood cultures of infective
      endocarditis patients in South India.

PMID- 18804350
TI  - Novel anti-microbial therapies for dental plaque-related diseases.
AB  - Control of dental plaque-related diseases has traditionally relied on non
      specific removal of plaque by mechanical means. As our knowledge of oral disease
      mechanisms increases, future treatment is likely to be more targeted, for example
      at small groups of organisms, single species or at key virulence factors they
      produce. The aim of this review is to consider the current status as regards
      novel treatment approaches. Maintenance of oral hygiene often includes use of
      chemical agents; however, increasing problems of resistance to synthetic
      antimicrobials have encouraged the search for alternative natural products.
      Plants are the source of more than 25% of prescription and over-the-counter
      preparations, and the potential of natural agents for oral prophylaxis will
      therefore be considered. Targeted approaches may be directed at the black
      pigmented anaerobes associated with periodontitis. Such pigments provide an
      opportunity for targeted phototherapy with high-intensity monochromatic light.
      Studies to date have demonstrated selective killing of Porphyromonas gingivalis
      and Prevotella intermedia in biofilms. Functional inhibition approaches,
      including the use of protease inhibitors, are also being explored to control
      periodontitis. Replacement therapy by which a resident pathogen is replaced with
      a non-pathogenic bacteriocin-producing variant is currently under development
      with respect to Streptococcus mutans and dental caries.

PMID- 18804351
TI  - Toxin-binding treatment for Clostridium difficile: a review including reports of
      studies with tolevamer.
AB  - Clostridium difficile represents an increasing threat to patients, mainly as a
      hospital-acquired infection causing antibiotic-associated colitis (AAC). The
      emergence of a new more virulent strain in North America and Europe has been
      linked to increased morbidity and mortality. For a long period of time the only
      available therapeutic options were oral vancomycin and metronidazole. However,
      both of these antibiotics have limitations either in terms of efficacy, cost,
      formulation, side effects or the risk of emerging antibiotic resistance among
      enterococci. Clostridium difficile produces two powerful toxins (A and B) that
      are responsible for the entire clinical spectrum associated with AAC. As this is
      exclusively a toxin-mediated disease, agents with the potential of binding these
      targets have been tested. Data on polymer-based toxin-binding agents such as
      cholestyramine, Synsorb 90 and tolevamer, designed to target specific bacterial
      toxins, will be reviewed. Bovine colostrum and specific human monoclonal
      antibodies aimed at neutralising toxin A, although still at an early stage of
      development, are also new avenues to be explored. Non-antibiotic-based therapies
      might become the best available option for a condition almost always caused by
      antibiotics.

PMID- 18804352
TI  - Metabolic changes in the brain of patients with late-onset major depression.
AB  - Positron emission tomography (PET) with fluorodeoxyglucose-F18 was used to
      examine glucose metabolism in patients with late-onset major depression, all
      hospitalized non-responders to antidepressant medication. The three-dimensional
      stereotactic surface projection (3D-SSP) method provided 3D-SSP images and
      relative metabolic values with minimal partial volume effects. The 3D-SSP score
      map showed decreased relative metabolism in the prefontal, cingulate and parietal
      regions in both hemispheres, and in the temporal region on the right, and
      increased relative metabolism in the occipital pole, vermis, cerebellum, dorsal
      frontal, central convexity areas and basal ganglia in both hemispheres in
      patients compared with controls. The ratio of the parietal to occipital values in
      right plus left hemispheres was significantly decreased. Correlation coefficients
      of the anterior cingulate-primary sensorimotor, posterior cingulate-primary
      sensorimotor and occipital-media frontal in both hemispheres, of the frontal
      primary sensorimotor, occipital-parahippocampal, primary visual-medial frontal
      and parahippocampal-amygdala in the right, and the frontal-vermis, parietal
      thalamus, temporal-vermis, occipital-putamen, primary visual-putamen, thalamus
      vermis and thalamus-cerebellum in the left were significantly different in
      patients compared with controls. Patients with late-onset depression who were
      treatment non-responders showed alterations not only in limbic-cortical circuits,
      but also in a wider network of thalamo-cortical circuits.

PMID- 18804353
TI  - Expression analysis of the exo-beta-1,3-glucanase from the mycoparasitic fungus
      Trichoderma asperellum.
AB  - The regulation of the gene encoding the extracellular exo-beta-1,3-glucanase
      (tag83) produced by the mycoparasite Trichoderma asperellum was studied. Enzyme
      activity was detected in all carbon sources, but the highest levels were found
      when starch and purified cell walls from Rhizoctonia solani were used. These
      results are supported by the appearance of one strong band with enzyme activity
      in non-denaturing PAGE. Experiments using RT-PCR showed that exo-beta-1,3
      glucanase induction in T. asperellum occurred at the transcriptional level. We
      used RT-PCR and real-time PCR analysis to examine the expression of tag83 gene
      during in vivo assay of T. asperellum against R. solani. We showed that the
      expression of tag83 is significantly increased by the presence of R. solani.

PMID- 18804354
TI  - Hemoptysis as a presenting sign of multiple myeloma.

PMID- 18804355
TI  - Epidemiology of community-acquired pneumonia in older adults: a population-based
      study.
AB  - OBJECTIVE: This study assessed incidence, aetiology, clinical outcomes and risk
      factors for community-acquired pneumonia (CAP) in older adults. METHODS: This was
      a population-based cohort study that included 11,241 community-dwelling
      individuals aged 65 years or more, who were followed between 2002 and 2005 in the
      region of Tarragona, Spain. Primary endpoints were all-cause CAP (hospitalised
      and outpatient) and 30-day mortality after the diagnosis. All cases were
      radiographically proved and validated by checking clinical records. RESULTS:
      Incidence rate of overall CAP was 14 cases per 1000 person-years (10.5 and 3.5
      for hospitalised and outpatient cases, respectively). Incidence was almost three
      fold higher among immunocompromised patients (30.9 per 1000) than among
      immunocompetent subjects (11.6 per 1000). Maximum incidences were observed among
      patients with chronic lung disease and long-term corticosteroid therapy (46.5 and
      40.1 cases per 1000 person-years, respectively). Overall 30-day case-fatality
      rate was 12.7% (2% in cases managed as outpatient and 15% in hospitalised
      patients). Among 358 patients with an aetiological work-up, a total of 142
      pathogens were found (single pathogen in 121 cases and mixed pathogens in 10
      cases). Streptococcus pneumoniae was the most common pathogen (49%), followed by
      Pseudomonas aeruginosa (15%), Chlamydia pneumoniae (9%) and Haemophilus
      influenzae (6%). In multivariable analysis, the variables most strongly
      associated with increasing risk of CAP were history of hospitalisation for CAP in
      the previous 2 years and presence of any chronic lung disease. CONCLUSIONS: CAP
      remains a major cause of morbidity and mortality in older adults. Incidence rates
      in this study largely doubled prior rates reported in Southern European regions.

PMID- 18804356
TI  - Acceptance, effectiveness and safety of continuous positive airway pressure in
      acute stroke: a pilot study.
AB  - OBJECTIVES: To evaluate the acceptance, effectiveness in preventing upper airways
      obstruction, and haemodynamic effects of continuous positive airway pressure
      (CPAP) in acute stroke. METHODS: Twelve patients (4 M, and 8 F; mean (SD), 75.2
      (5.5) years) within 48 h of acute stroke onset underwent: (1) sleep studies (1st
      night: auto-CPAP mode; 2nd night: diagnostic); (2) nocturnal non-invasive blood
      pressure studies (1st night during CPAP; 2nd night during spontaneous breathing
      (SB)); and (3) daytime cerebral blood flow velocity measurement in middle
      cerebral artery (FV) with transcranial Doppler during SB and with CPAP (5, 10, 15
      cm H(2)O). RESULTS: Ninety percent, 60% and 50% of stroke patients had a
      respiratory disturbance index (RDI) of >or=5, >or=10 and >or=15 events per hour,
      respectively (18.2 (11.3)). CPAP acceptance was 84%; 42% used CPAP more than 6h
      and 42% between 1-3h with a mean use of CPAP of 5.2h (4.0). Compared to SB, CPAP
      reduced, though not significantly, RDI, time with SaO(2)<90%, mean blood pressure
      and mean blood pressure dips (10 mm Hg)/h. Compared with SB, any level of CPAP
      progressively and significantly reduced systolic and mean FV; drop in diastolic
      FV was significant at CPAP10 and CPAP15. The partial pressure of end-tidal CO(2)
      was significantly lowered by all levels of CPAP. CONCLUSIONS: According to this
      pilot study, CPAP is reasonably well tolerated by patients with acute stroke for
      at least one night. Despite its possible beneficial effect on obstructive sleep
      disordered breathing and blood pressure variability, CPAP use in acute stroke
      should be still considered with caution due to possible harmful haemodynamic
      effects at higher pressures.

PMID- 18804357
TI  - Impact of noninvasive ventilation (NIV) trial for various types of acute
      respiratory failure in the emergency department; decreased mortality and use of
      the ICU.
AB  - BACKGROUND: Trial of noninvasive ventilation (NIV) in the emergency department
      (ED) for heterogeneous acute respiratory failure (ARF) has been optional and its
      clinical benefit unclear. METHODS: We conducted a retrospective cohort study
      comparing between two periods, October 2001-September 2003 and October 2004
      September 2006, i.e., before and after adopting an NIV-trial strategy in which
      NIV was applied in the ED to any noncontraindicated ARF patients needing
      ventilatory support and was then continued in the intermediate-care-unit. During
      these two periods, we retrieved cases of ARF treated either invasively or with
      NIV, and compared the patients' in-hospital mortalities and the length of ICU and
      intermediate-care-unit stay. RESULTS: Compared were 73 (invasive 56, NIV 17) and
      125 cases (invasive 31, NIV 94) retrieved from 271 and 415 emergent admissions
      with proper pulmonary etiologies for mechanical ventilation, respectively. Of
      their respiratory failures, type (hypercapnic/non-hypercapnic, 0.97 vs. 0.98) and
      severity (pH 7.23 vs. 7.21 for hypercapnic; PaO(2)/FiO(2) 133 vs. 137 for non
      hypercapnic) were similar, and the rate of predisposing etiologies was not
      significantly different. However, excluding those with recurrent aspiration
      pneumonia for whom NIV was mostly used as "ceiling" treatment, significant
      reductions in both overall in-hospital mortality (38%-19%, risk ratio 0.51, 95%
      CI 0.31-0.84), and median length of ICU and intermediate-care-unit stay (12 vs. 5
      days, P<0.0001) were found. CONCLUSIONS: NIV-trial in the ED for all possible
      patients with ARF of pulmonary etiologies, excluding those with recurrent
      aspiration pneumonia, may reduce overall in-hospital mortality and ICU stays.

PMID- 18804358
TI  - Treatments for pulmonary sarcoidosis.

PMID- 18804359
TI  - Reduced vital capacity after methacholine challenge in early childhood--is it due
      to trapped air or loss of motivation.
AB  - In a previous study we assessed the feasibility of measuring bronchial-reactivity
      (BHR) in young asthmatic children by the determination of PC(20)-FEV(1) along
      with clinical end-of-test criteria during a methacholine challenge test (MCT).
      The end-point was associated with a significant reduction in both flow and vital
      capacity values. The findings could be due to the children's loss of motivation,
      which may preclude use of this test. Alternatively, if it reflects air trapping
      during airway obstruction, it might reinforce its applicability in preschool age
      children. OBJECTIVES: To elucidate the mechanism of low vital capacity at PC(20)
      FEV(1) in preschool age children. SUBJECTS: Twenty-eight children (3.3-6.9 years)
      with recurrent respiratory symptoms. METHODS: An MCT was carried out using
      tripling doses (0.06-13.9 mg/ml) delivered by a dosimeter. Spirometry was
      measured at baseline and after each inhalation in duplicate sets. Whole body
      plethysmography was measured at baseline and at end-of-test (defined by clinical
      criteria) according to the recommendations for older populations. RESULTS:
      Plethysmography was reliably performed by 20 children before and after MCT. At
      baseline, lung function was within the healthy range. At end-of-test (PC(20)
      FEV(1)=4.02+/-3.47 mg/ml), the spirometry parameters and specific conductance
      values were markedly reduced in correlation with a significant increase in
      residual volume and resistance. CONCLUSIONS: The study shows that diminished
      vital capacity is due to the increase in FRC at end-of-test. Our findings support
      the use of PC(20)-FEV(1) during BHR in young children and suggest that lung
      volume measurement by a plethysmograph may be feasible in early childhood. Larger
      studies should be performed to establish the clinical applicability of PC20-FEV1
      determination in the preschool age.

PMID- 18804360
TI  - Impact of pulmonary hypertension on gas exchange and exercise capacity in
      patients with pulmonary fibrosis.
AB  - Pulmonary hypertension is a relevant interceding morbidity in patients with
      pulmonary fibrosis that has significant impact on exercise tolerance and outcome.
      The aim of this study was to further characterize the exercise intolerance,
      dyspnoea and ventilatory inefficiency of patients with pulmonary fibrosis in the
      presence or absence of pulmonary hypertension via cardiopulmonary exercise
      testing. Thirty-four patients underwent pulmonary function testing, symptom
      limited exercise testing on a bicycle and dyspnoea evaluation according to the
      BORG scale. Pulmonary hypertension was assessed by echocardiography and in a
      subset of patient's right heart catheterization. Sixteen of 34 patients with
      pulmonary fibrosis revealed pulmonary hypertension. While all study patients did
      not differ in lung functions and demographic characteristics, patients suffering
      from pulmonary hypertension showed a significantly impaired exercise tolerance
      and worsened ventilatory inefficiency. The extent of pulmonary artery pressure
      elevation impacted significantly on ventilatory inefficiency. In addition, the
      increased ventilatory requirements significantly influenced the extent of
      dyspnoea in patients with pulmonary hypertension. We conclude that pulmonary
      hypertension has a significant impact on exercise capacity and dyspnoea in
      patients with interstitial lung disease (ILD). The further impairment of exercise
      capacity as well as the extent of dyspnoea in patients with interceding PHT is
      attributable to a significantly impaired ventilatory inefficiency.

PMID- 18804361
TI  - Postextubation pulmonary edema: a case series and review.
AB  - We report a series of patients with postextubation pulmonary edema who had no
      obvious risk factors for the development of this syndrome. METHODS: Patients
      identified by the pulmonary consultation service at an academic medical center
      were reviewed. RESULTS: Fourteen cases were collected and analyzed. The average
      age was 34.5 years; 12 patients were male. The average BMI was 25.5. None had
      documented previous lung disease. Most operations were scheduled as outpatient
      procedures, and the type of surgery ranged from an incision and drainage of a
      bite wound to an open reduction-internal fixation of the radius. None of the
      patients had upper airway surgery. The length of surgeries ranged from 27 to 335
      min. Laryngospasm was the most commonly identified obstructing event
      postextubation. Treatment involved airway support when needed, supplemental
      oxygen, and diuretics. CONCLUSIONS: It would appear that all patients, especially
      young men, are at risk for the development of this syndrome and that the
      pathogenesis remains uncertain in many cases.

PMID- 18804362
TI  - Formoterol mono- and combination therapy with tiotropium in patients with COPD: a
      6-month study.
AB  - Although guidelines recommend combining long-acting bronchodilators in COPD, data
      are limited. We examined the clinical efficacy and safety of formoterol,
      tiotropium and the combination in patients with COPD. Eight hundred and forty
      seven patients with COPD (mean FEV(1) 52% predicted; FEV(1)/FVC 53%) were
      randomized to receive one of the following four treatments for 24 weeks:
      formoterol 10 microg b.i.d. plus tiotropium 18 microg o.d.; formoterol 10 microg
      b.i.d.; tiotropium 18 microg o.d., or placebo. The study was partially blinded
      (formoterol and placebo). For the primary endpoint, FEV(1) 2h post-dose after 24
      weeks, there were small differences in favour of the combination therapy versus
      formoterol (0.07 L, p=0.044) or tiotropium (0.06 L, p=0.066). All three
      treatments were superior to placebo (p<0.001). The combination was statistically
      superior to monotherapy for: the primary endpoint (p=0.044 vs. formoterol);
      FEV(1) 5 min after the first dose (p<0.001) and at 12 weeks (p<0.05 vs.
      tiotropium); and peak expiratory flow averaged over the first 6 weeks (p<0.001
      vs. both). The three active treatments were significantly more effective than
      placebo for secondary endpoints: COPD-related 'bad days', symptoms, use of rescue
      medication and peak expiratory flow, and aspects of health-related quality of
      life. The overall incidence of adverse events was similar with all active
      treatments, although COPD-related adverse events were more common with
      tiotropium. Combined bronchodilator therapy may be a valuable treatment option
      for patients with COPD.

PMID- 18804363
TI  - Estimation of mass transport parameters of gases for quantifying CH4 oxidation in
      landfill soil covers.
AB  - Methane (CH(4)), which is one of the most abundant anthropogenic greenhouse
      gases, is produced from landfills. CH(4) is biologically oxidized to carbon
      dioxide, which has a lower global warming potential than methane, when it passes
      through a cover soil. In order to quantify the amount of CH(4) oxidized in a
      landfill cover soil, a soil column test, a diffusion cell test, and a
      mathematical model analysis were carried out. In the column test, maximum
      oxidation rates of CH(4) (V(max)) showed higher values in the upper part of the
      column than those in the lower part caused by the penetration of O(2) from the
      top. The organic matter content in the upper area was also higher due to the
      active microbial growth. The dispersion analysis results for O(2) and CH(4) in
      the column are counter-intuitive. As the upward flow rate of the landfill gas
      increased, the dispersion coefficient of CH(4) slightly increased, possibly due
      to the effect of mechanical dispersion. On the other hand, as the upward flow
      rate of the landfill gas increased, the dispersion coefficient of O(2) decreased.
      It is possible that the diffusion of gases in porous media is influenced by the
      counter-directional flow rate. Further analysis of other gases in the column,
      N(2) and CO(2), may be required to support this hypothesis, but in this paper we
      propose the possibility that the simulations using the diffusion coefficient of
      O(2) under the natural condition may overestimate the penetration of O(2) into
      the soil cover layer and consequently overestimate the oxidation of CH(4).

PMID- 18804364
TI  - Charging systems for municipal solid waste: experience from the Czech Republic.
AB  - The paper presents results of research into municipal waste treatment in the
      Czech Republic. Its special focus is on the impacts of various municipal solid
      waste charging systems on separating and recycling efforts of municipalities and
      households. The municipal solid waste charging systems are shortly described
      first, including the principles of the relevant Czech legislation. It shows that
      the Czech waste legislation provides space for implementing Pay-as-You-Throw
      (PAYT) models in the Czech Republic. The main results of representative surveys
      conducted by the authors within the EU PAYT project in 2003 in selected Czech
      municipalities and Prague households are shown. The survey confirmed that in
      municipalities that apply the PAYT charging system, citizens separate more waste
      and produce less residual waste. The survey data analysis has also shown which
      factors contributing to satisfactory waste separation are relevant and should be
      taken into the account when providing policy recommendations for introducing PAYT
      charging systems in other cities.

PMID- 18804365
TI  - Rapid detection of Bacillus anthracis using monoclonal antibody functionalized
      QCM sensor.
AB  - Since the anthrax spore bioterrorism attacks in America in 2001, the early
      detection of Bacillus anthracis spores and vegetative cells has gained
      significant interest. At present, many polyclonal antibody-based quartz crystal
      microbalance (QCM) sensors have been developed to detect B. anthracis simulates.
      To achieve a simultaneous rapid detection of B. anthracis spores and vegetative
      cells, this paper presents a biosensor that utilizes an anti-B. anthracis
      monoclonal antibody designated to 8G3 (mAb 8G3, IgG) functionalized QCM sensor.
      Having compared four kinds of antibody immobilizations on Au surface, an
      optimized mAb 8G3 was immobilized onto the Au electrode with protein A on a mixed
      self-assembled monolayer (SAM) of 11-mercaptoundecanoic acid (11-MUA) and 6
      mercaptohexan-1-ol (6-MHO) as adhesive layer. The detection of B. anthracis was
      investigated under three conditions: dip-and-dry, static addition and flow
      through procedure. The results indicated that the sensor yielded a distinct
      response to B. anthracis spores or vegetative cells but had no significant
      response to Bacillus thuringiensis species. The functionalized sensor recognized
      B. anthracis spores and vegetative cells specifically from its homophylic ones,
      and the limit of detection (LOD) reached 10(3)CFU or spores/ml of B. anthracis in
      less than 30 min. Cyclic voltammogram (CV) and scanning electronic microscopy
      (SEM) were performed to characterize the surface of the sensor in variable steps
      during the modification and after the detection. The mAb functionalized QCM
      biosensor will be helpful in the fabrication of a similar biosensor that may be
      available in anti-bioterrorism in the future.

PMID- 18804366
TI  - Fabrication of size-controllable ultrasmall-disk electrode: monitoring single
      vesicle release kinetics at tiny structures with high spatio-temporal resolution.
AB  - Size-controllable micron or nano-disk carbon fiber electrode (CFE) is prepared
      and demonstrated to be excellent for extra-cellular transmitter release detection
      at tiny structures and vesicle fusion kinetics analysis with high spatio-temporal
      resolution. An improved electrochemical etching procedure was employed, for the
      first time, to fabricate cylindrical fiber with controlled micron or nano
      diameter. Afterwards, a facile insulation with polypropylene sheath was employed
      to completely insulate the whole body of the thinned fiber, and an ultrasmall
      disk sensing area was finally produced by cutting of the insulated fibers.
      Scanning electron microscopy (SEM) was employed to characterize the ultrasmall
      geometry size of the fabricated electrode and to show the tight adherence of the
      insulation sheath on the fiber. The cut ends of the electrodes were also shown to
      be smooth, clean and without obvious jagged layer. The fabricated micron or nano
      disk carbon electrodes show ideal steady-state voltammetric behavior with
      satisfying reversibility. Subsequently, the performance of the ultrasmall-disk
      CFE for amperometric detection of cell secretion was characterized. Results
      showed that, compared to the conventional micro-disk CFE, the etched small disk
      CFE possesses higher sensitivity due to its obviously improved signal-to-noise
      level, which enables minute amounts of 3000 oxidizable molecules to be
      detectable. The nano-disk CFE was shown to be particularly ideal for analysis of
      fusion kinetics, due to its avoidance of diffusion broadening of the detected
      spikes, which is the inherent defect of the conventional micro-CFE technique.

PMID- 18804367
TI  - A novel nitrite biosensor based on conductometric electrode modified with
      cytochrome c nitrite reductase composite membrane.
AB  - A conductometric biosensor for nitrite detection was developed using cytochrome c
      nitrite reductase (ccNiR) extracted from Desulfovibrio desulfuricans ATCC 27774
      cells immobilized on a planar interdigitated electrode by cross-linking with
      saturated glutaraldehyde (GA) vapour in the presence of bovine serum albumin,
      methyl viologen (MV), Nafion, and glycerol. The configuration parameters for this
      biosensor, including the enzyme concentration, ccNiR/BSA ratio, MV concentration,
      and Nafion concentration, were optimized. Various experimental parameters, such
      as sodium dithionite added, working buffer solution, and temperature, were
      investigated with regard to their effect on the conductance response of the
      biosensor to nitrite. Under the optimum conditions at room temperature (about 25
      degrees C), the conductometric biosensor showed a fast response to nitrite (about
      10s) with a linear range of 0.2-120 microM, a sensitivity of 0.194 microS/microM
      [NO(2)(-)], and a detection limit of 0.05 microM. The biosensor also showed
      satisfactory reproducibility (relative standard deviation of 6%, n=5). The
      apparent Michaelis-Menten constant (K(M,app)) was 338 microM. When stored in
      potassium phosphate buffer (100mM, pH 7.6) at 4 degrees C, the biosensor showed
      good stability over 1 month. No obvious interference from other ionic species
      familiar in natural waters was detected. The application experiments show that
      the biosensor is suitable for use in real water samples.

PMID- 18804368
TI  - Comparison of a potentiometric and a micromechanical triglyceride biosensor.
AB  - Sensitive biosensors for detection of triglyceride concentration are important.
      In this paper we report on two types of silicon based triglyceride sensors: an
      electrolyte-insulator-semiconductor capacitor (EISCAP) which is a potentiometric
      device and a polysilicon microcantilever. The detection principle for both
      sensors is based on the enzymatic hydrolysis of triglyceride though the sensing
      mechanisms are different: electronic for the EISCAP and mechanical for the
      microcantilever. The characteristics and performances of the two sensors are
      critically compared. The EISCAP sensor necessitates the presence of a buffer for
      stable measurements which limits the sensitivity of the sensor at low
      concentrations of the bioanalyte to 1mM. The cantilever sensor works without a
      buffer which improves the lower level of sensitivity to 10 microm. Both sensors
      are found to give reproducible and reliable results.

PMID- 18804369
TI  - Small, non-peptide C5a receptor antagonists: part 2.
AB  - Starting from 2, several highly potent C5a receptor antagonists were synthesised
      through alpha-amide substitution. Attempts to increase the polarity of these
      compounds through the introduction of basic centres or incorporation into weakly
      basic heterocycles is described.

PMID- 18804370
TI  - Eicosapentaenoic-acid-derived isoprostanes: synthesis and discovery of two major
      isoprostanes.
AB  - The stereospecific synthesis of two all-syn-EPA-derived isoprostanes (iPs), 5-epi
      8,12-iso-iPF(3alpha)-VI 17 and 8,12-iso-iPF(3alpha)-VI 18, has been accomplished.
      These two synthetic probes have been used to discover and identify their presence
      in human urine. The eventual quantitative measurement of these two iPs may be a
      valuable index of oxidative stress in people with eicosapentaenoic acid- (EPA)
      and docosahexaenoic acid- (DHA) enriched phospholipids.

PMID- 18804371
TI  - Differential stability of flamingo protein complexes underlies the establishment
      of planar polarity.
AB  - BACKGROUND: The planar polarization of developing tissues is controlled by a
      conserved set of core planar polarity proteins. In the Drosophila pupal wing,
      these proteins adopt distinct proximal and distal localizations in apicolateral
      junctions that act as subcellular polarity cues to control morphological events.
      The core polarity protein Flamingo (Fmi) localizes to both proximal and distal
      cell boundaries and is known to have asymmetric activity, but the molecular basis
      of this asymmetric activity is unknown. RESULTS: We examine the role of Fmi in
      controlling asymmetric localization of polarity proteins in pupal wing cells. We
      find that Fmi interacts preferentially with distal-complex components, rather
      than with proximal components, and present evidence that there are different
      domain requirements for Fmi to associate with distal and proximal components. We
      further show that distally and proximally localized proteins cooperate to allow
      stable accumulation of Fmi at apicolateral junctions and present evidence that
      the rates of endocytic trafficking of Fmi are increased when Fmi is not in a
      stable asymmetric complex. Finally, we provide evidence that Fmi is trafficked
      from junctions via both Dishevelled-dependent and Dishevelled-independent
      mechanisms. CONCLUSIONS: We present a model in which the primary function of Fmi
      is to participate in the formation of inherently stable asymmetric junctional
      complexes: Removal from junctions of Fmi that is not in stable complexes,
      combined with directional trafficking of Frizzled and Fmi to the distal cell
      edge, drives the establishment of cellular asymmetry.

PMID- 18804372
TI  - Genetic variability and robustness of host odor preference in Drosophila
      melanogaster.
AB  - Chemosensory stimuli play a crucial role for host selection in insects, including
      the fruit fly Drosophila melanogaster. Drosophila has been instrumental in
      unraveling the neurological basis of olfactory processing in insects. Basic
      knowledge regarding chemical ecology and thorough studies of olfactory
      preferences are still lacking to a great extent in D. melanogaster, however. We
      have characterized repeatable variation in olfactory preference between five
      classical D. melanogaster wild-type strains toward a large array of natural host
      odors and synthetic compounds. By recording the rate of attraction over up to 24
      hr, we could compare stimuli varying in attractiveness and characterize
      phenotypic parameters on the basis of individual stimuli and the whole stimulus
      array. Behavioral differences between strains were predominantly due to variation
      in a single phenotypic parameter: their overall responsiveness toward optimal and
      suboptimal olfactory stimuli. These differences were not explained by variation
      in olfactory sensitivity, locomotory activity, or general vigor monitored by
      survival. Comparisons with three recently established wild-type strains indicated
      that a high behavioral threshold against accepting suboptimal olfactory stimuli
      is the characteristic phenotype of wild D. melanogaster.

PMID- 18804373
TI  - A role for very-long-chain fatty acids in furrow ingression during cytokinesis in
      Drosophila spermatocytes.
AB  - Cell shape and membrane remodeling rely on regulated interactions between the
      lipid bilayer and cytoskeletal arrays at the cell cortex. During cytokinesis,
      animal cells build an actomyosin ring anchored to the plasma membrane at the
      equatorial cortex. Ring constriction coupled to plasma-membrane ingression
      separates the two daughter cells. Plasma-membrane lipids influence membrane
      biophysical properties such as membrane curvature and elasticity and play an
      active role in cell function, and specialized membrane domains are emerging as
      important factors in regulating assembly and rearrangement of the cytoskeleton.
      Here, we show that mutations in the gene bond, which encodes a Drosophila member
      of the family of Elovl proteins that mediate elongation of very-long-chain fatty
      acids, block or dramatically slow cleavage-furrow ingression during early
      telophase in dividing spermatocytes. In bond mutant cells at late stages of
      division, the contractile ring frequently detaches from the cortex and constricts
      or collapses to one side of the cell, and the cleavage furrow regresses. Our
      findings implicate very-long-chain fatty acids or their derivative complex lipids
      in allowing supple membrane deformation and the stable connection of cortical
      contractile components to the plasma membrane during cell division.

PMID- 18804374
TI  - Behavioral and prefrontal representation of spatial proportions in the monkey.
AB  - Primate brains are equipped with evolutionarily old and dedicated neural circuits
      so that they can grasp absolute quantities, such as the number of items or the
      length of a line. Absolute magnitude, however, is often not informative enough to
      guide decisions in conflicting social and foraging situations that require an
      assessment of quantity ratios. We report that rhesus monkeys can discriminate
      proportions (1:4, 2:4, 3:4, and 4:4) specified by bars differing in lengths and
      that they can do so at a precision comparable to that shown by humans; the
      monkeys thus demonstrate an abstract understanding of proportionality. Moreover,
      neurons in the lateral prefrontal cortex selectively responded to preferred
      proportions regardless of the exact physical appearance of the stimuli. These
      results support the hypothesis that nonhuman primates can judge proportions and
      utilize the underlying information in behaviorally relevant situations.

PMID- 18804375
TI  - Fission-fusion dynamics, behavioral flexibility, and inhibitory control in
      primates.
AB  - The Machiavellian Intelligence or Social Brain Hypothesis explains the evolution
      of increased brain size as mainly driven by living in complex organized social
      systems in which individuals represent "moving targets" who can adopt multiple
      strategies to respond to one another. Frequently splitting and merging in
      subgroups of variable composition (fission-fusion or FF dynamics) has been
      proposed as one aspect of social complexity ( compare with) that may be
      associated with an enhancement of cognitive skills like inhibition, which allows
      the suppression of prepotent but ineffective responses in a changing social
      environment. We compared the performance of primates experiencing high levels of
      FF dynamics (chimpanzees, bonobos, orangutans, and spider monkeys) to that of
      species living in more cohesive groups (gorillas, capuchin monkeys, and long
      tailed macaques) on five inhibition tasks. Testing species differing in diet,
      phylogenetic relatedness, and levels of FF dynamics allowed us to contrast
      ecological, phylogenetic, and socioecological explanations for interspecific
      differences. Spider monkeys performed at levels comparable to chimpanzees,
      bonobos, and orangutans, and better than gorillas. A two-cluster analysis grouped
      all species with higher levels of FF dynamics together. These findings confirmed
      that enhanced inhibitory skills are positively associated with FF dynamics, more
      than to phylogenetic relations or feeding ecology.

PMID- 18804376
TI  - A bacterium targets maternally inherited centrosomes to kill males in Nasonia.
AB  - Male killing is caused by diverse microbial taxa in a wide range of arthropods.
      This phenomenon poses important challenges to understanding the dynamics of sex
      ratios and host-pathogen interactions. However, the mechanisms of male killing
      are largely unknown. Evidence from one case in Drosophila suggests that bacteria
      can target components of the male-specific sex-determination pathway. Here, we
      investigated male killing by the bacterium Arsenophonus nasoniae in the haplo
      diploid wasp Nasonia vitripennis, in which females develop as diploids from
      fertilized eggs and males develop parthenogenetically as haploids from
      unfertilized eggs. We found that Arsenophonus inhibits the formation of maternal
      centrosomes, organelles required specifically for early male embryonic
      development, resulting in unorganized mitotic spindles and developmental arrest
      well before the establishment of somatic sexual identity. Consistent with these
      results, rescue of Arsenophonus-induced male lethality was achieved by
      fertilization with sperm bearing the supernumerary chromosome paternal sex ratio
      (PSR), which destroys the paternal genome but bypasses the need for maternal
      centrosomes by allowing transmission of the sperm-derived centrosome into the
      egg. These findings reveal a novel mechanism of male killing in Nasonia,
      demonstrating that bacteria have evolved different mechanisms for inducing male
      killing in the Arthropods.

PMID- 18804377
TI  - The DHHC palmitoyltransferase approximated regulates Fat signaling and Dachs
      localization and activity.
AB  - Signaling via the large protocadherin Fat (Ft), regulated in part by its binding
      partner Dachsous (Ds) and the Golgi-resident kinase Four-jointed (Fj), is
      required for a variety of developmental functions in Drosophila. Ft and, to a
      lesser extent, Ds suppress overgrowth of the imaginal discs from which appendages
      develop and regulate the Hippo pathway [1-5] (reviewed in [6]). Ft, Ds, and Fj
      are also required for normal planar cell polarity (PCP) in the wing, abdomen, and
      eye and for the normal patterning of appendages, including the spacing of
      crossveins in the wing and the segmentation of the leg tarsus (reviewed in [7
      9]). Ft signaling was recently shown to be negatively regulated by the atypical
      myosin Dachs [10, 11]. We identify here an additional negative regulator of Ft
      signaling in growth control, PCP, and appendage patterning, the Approximated
      (App) protein. We show that App encodes a member of the DHHC family, responsible
      for the palmitoylation of selected cytoplasmic proteins, and provide evidence
      that App acts by controlling the normal subcellular localization and activity of
      Dachs.

PMID- 18804379
TI  - Synthesis and antituberculosis activity of 5-methyl/trifluoromethoxy-1H-indole
      2,3-dione 3-thiosemicarbazone derivatives.
AB  - New series of 5-methyl/trifluoromethoxy-1H-indole-2,3-dione 3-thiosemicarbazones
      3a-t, 1-methyl-5-methyl/trifluoromethoxy-1H-indole-2,3-dione 3-thiosemicarbazones
      4a-y and 5-trifluoromethoxy-1-morpholinomethyl-1H-indole-2,3-dione 3
      thiosemicarbazones 5a-m were synthesized. The structures of the synthesized
      compounds were confirmed by spectral data and elemental analysis. The new 5
      methyl/trifluoromethoxy-1H-indole-2,3-dione derivatives, along with previously
      synthesized 5-methyl-1H-indole-2,3-dione 3-thiosemicarbazones 6a-l, were
      evaluated for in vitro antituberculosis activity against Mycobacterium
      tuberculosis H37Rv. 5-Methyl-1H-indole-2,3-dione 3-thiosemicarbazones (3b, 3d,
      3f, 6c, 6d, and 6f), 5-trifluoromethoxy-1H-indole-2,3-dione 3-thiosemicarbazones
      (3q-s) and 5-trifluoromethoxy-1-morpholinomethyl-1H-indole-2,3-dione 3
      thiosemicarbazones (5e and 5j-l) were found to be the most potent inhibitors of
      M. tuberculosis growth described in this study.

PMID- 18804378
TI  - The Target of Rapamycin pathway antagonizes pha-4/FoxA to control development and
      aging.
AB  - BACKGROUND: FoxA factors are critical regulators of embryonic development and
      postembryonic life, but little is know about the upstream pathways that modulate
      their activity. C. elegans pha-4 encodes a FoxA transcription factor that is
      required to establish the foregut in embryos and to control growth and longevity
      after birth. We previously identified the AAA+ ATPase homolog ruvb-1 as a potent
      suppressor of pha-4 mutations. RESULTS: Here we show that ruvb-1 is a component
      of the Target of Rapamycin (TOR) pathway in C. elegans (CeTOR). Both ruvb-1 and
      let-363/TOR control nucleolar size and promote localization of box C/D snoRNPs to
      nucleoli, suggesting a role in rRNA maturation. Inactivation of let-363/TOR or
      ruvb-1 suppresses the lethality associated with reduced pha-4 activity. The CeTOR
      pathway controls protein homeostasis and also contributes to adult longevity. We
      find that pha-4 is required to extend adult lifespan in response to reduced CeTOR
      signaling. Mutations in the predicted CeTOR target rsks-1/S6 kinase or in ife
      2/eIF4E also reduce protein biosynthesis and extend lifespan, but only rsks-1
      mutations require pha-4 for adult longevity. In addition, rsks-1, but not ife-2,
      can suppress the larval lethality associated with pha-4 loss-of-function
      mutations. CONCLUSIONS: The data suggest that pha-4 and the CeTOR pathway
      antagonize one another to regulate postembryonic development and adult longevity.
      We suggest a model in which nutrients promote TOR and S6 kinase signaling, which
      represses pha-4/FoxA, leading to a shorter lifespan. A similar regulatory
      hierarchy may function in other animals to modulate metabolism, longevity, or
      disease.

PMID- 18804380
TI  - Isolation, structure, and antibacterial activity of thiazomycin A, a potent
      thiazolyl peptide antibiotic from Amycolatopsis fastidiosa.
AB  - Thiazolyl peptides are a class of thiazole-rich macrocyclic potent antibacterial
      agents. Recently, we described thiazomycin, a new member of thiazolyl peptides,
      discovered by a thiazolyl peptide specific chemical screening. This method also
      allowed for the discovery of a new thiazolyl peptide, thiazomycin A, which
      carries modification in the oxazolidine ring of the amino sugar moiety.
      Thiazomycin A is a specific inhibitor of protein synthesis (IC(50) 0.7 microg/mL)
      and a potent Gram-positive antibacterial agent with minimum inhibitory
      concentration (MIC) ranging 0.002-0.25 microg/mL. The isolation and structure
      elucidation and biological activities of thiazomycin A are described.

PMID- 18804381
TI  - Principles of demineralization: modern strategies for the isolation of organic
      frameworks. Part II. Decalcification.
AB  - This is the second paper on principles of demineralization. The initial paper is
      dedicated to the common definitions and the history of demineralization. In
      present work we review the principles and mechanisms of decalcification, i.e.,
      removing the mineral Ca-containing compounds (phosphates and carbonates) from the
      organic matrix in its two main aspects: natural and artificial. Natural chemical
      erosion of biominerals (cavitation of biogenic calcareous substrata by bacteria,
      fungi, algae, foraminifera, sponges, polychaetes, and mollusks) is driven by
      production of mineral and organic acids, acidic polysaccharides, and enzymes
      (cabonic anhydrase, alkaline and phosphoprotein phosphataes, and H(+)-ATPase).
      Examples of artifical decalcification includes demineralization of bone, dentin
      and enamel, and skeletal formations of corals and crustacean. The mechanism and
      kinetics of Ca-containing biomineral dissolution is analyzed within the framework
      of (i) diffusion-reaction theory; (ii) surface-reaction controlled, morphology
      based theories, and (iii) phenomenological surface coordination models. The
      application of surface complexation model for describing and predicting the
      effect of organic ligands on calcium and magnesium dissolution kinetics is also
      described. Use of the electron microscopy-based methods for observation and
      visualization of the decalcification phenomenon is discussed.

PMID- 18804382
TI  - The role of surgery and radiotherapy in treatment of soft tissue sarcomas of the
      head and neck region: review of 30 cases.
AB  - BACKGROUND: Thirty adult patients with head and neck soft tissue sarcoma (HNSTS)
      treated between 1987 and 2000 were retrospectively analysed. PATIENTS AND
      METHODS: The most frequent histopathological subtypes were chondrosarcomas (27%)
      and malignant fibrous histiocytoma (20%). The surgical resection was performed in
      25 of the 30 patients (83%). Twenty-three patients in the surgical resection arm
      received postoperative radiotherapy. RESULTS: Five-year local control rates for
      patients with negative surgical margins (n=9), microscopically positive disease
      (n=10), gross residual disease (n=6) and inoperable cases (n=5) were 64, 70, 20
      and 0%, respectively. However, there was no significant difference in local
      control between patients with negative or microscopically positive disease who
      received postoperative radiotherapy (71 vs. 70%). The patients who received
      doses>or=60 Gy had significantly higher local control rates than the ones who
      received doses lower than 60 Gy (p=0.048). The local control rates were lower in
      patients with grade 2-3 tumours when compared with grade 1 tumours (44 vs. 83%).
      The median overall survival of whole group was 31 months. Median survivals of
      patients receiving both surgery and radiotherapy with negative and
      microscopically positive margins were significantly better than patients who were
      not treated with surgery (34.8 and 36 vs. 13.3 months). CONCLUSION: Our results
      confirm that the optimal treatment of HNSTSs is complete surgical excision, and
      that postoperative adjuvant radiotherapy clearly improves local control.

PMID- 18804383
TI  - Is mitochondrial dysfunction a cause of insulin resistance?
AB  - Insulin resistance is a key defect associated with obesity and type-2 diabetes.
      The precise factors that lead to insulin resistance have not been elucidated
      fully, but there is a strong association between insulin resistance and
      inappropriate lipid accumulation in insulin-target tissues. Over the past decade,
      several studies have reported changes in markers of mitochondrial metabolism in
      insulin-resistant individuals. These observations have led to the theory that
      compromised mitochondrial oxidative function, particularly in skeletal muscle,
      causes excess lipid deposition and the development of insulin resistance. Here,
      we review the latest findings regarding the link between mitochondrial metabolism
      and insulin action and, in particular, highlight several recent studies that call
      into question the cause-and-effect relationship between mitochondrial dysfunction
      and insulin resistance.

PMID- 18804384
TI  - TGF-beta1 and IL-6 gene polymorphism in Spanish brucellosis patients.
AB  - Polymorphisms in the cytokine genes have allowed for the understanding of the
      genetic determinants in several diseases. We investigated the polymorphism of the
      transforming growth factor (TGF)-beta1 and IL-6 genes in relation to
      susceptibility to human brucellosis. We typed 82 Spanish brucellosis patients and
      102 healthy controls for TGF-beta1 polymorphisms in codons 10 and 25, and IL-6
      promoter polymorphism at position -174 by PCR-SSP methods. The T/T G/G genotype
      of the TGF-beta1 gene was significantly increased in patients compared to
      controls (49% vs. 32%) P=0.02; OR=1.99 (1.05-3.80) and the T/C G/G genotype was
      significantly less common in the patients compared to the controls (32% vs. 49%)
      P=0.01; OR=0.48 (0.25-0.92). The CC genotype of codon 10 was significantly
      increased in the patients who had focal forms of the disease as compared with
      those who did not develop focal forms (19% vs. 4%), P=0.03; OR=0.19 (0.02-1.10).
      No differences were found in the IL-6 variants between the patients and the
      controls. These results suggest that polymorphism of the TGF-beta1 gene may be
      involved in susceptibility to brucellosis and to developing focal forms of the
      disease in a group of patients from southern Spain.

PMID- 18804385
TI  - Mass-based classification (MBC) of peptides: highly accurate precursor ion mass
      values can be used to directly recognize peptide phosphorylation.
AB  - Accurate mass values as obtainable by Fourier transform ion cyclotron resonance
      mass spectrometry (FTICR-MS) were employed in a theoretical study to
      differentiate between nonmodified and phosphorylated peptides. It was found that
      for peptide masses up to 1,000 u more than 98% of all theoretical
      monophosphorylated peptides (all possible combinations of proteinogenic amino
      acids having one phosphorylation on S, T, or Y) can be distinguished from
      nonphosphorylated peptides directly by their mass, if mass values are determined
      with an accuracy of better than +/-0.1 ppm. At a peptide mass of 1,500 u still
      70% of all possible monophosphorylated peptides are distinguishable from
      nonmodified peptides by their accurate mass alone. In contrast to established
      techniques of data-dependent multidimensional mass spectrometry, only the mass of
      the precursor ion is necessary to decide upon subsequent fragment ion analysis of
      a peptide for sequence analysis in an LC-MS/MS investigation of a complex sample,
      when using a precalculated mass distribution table of theoretical peptides. A
      mass distribution table of nonphosphorylated and monophosphorylated peptides with
      a bin width of 0.1 mu was made available via the open web site
      www.peptidecomposer.com.

PMID- 18804387
TI  - Development of a novel recombinant influenza vaccine in insect cells.
AB  - Influenza is a highly contagious viral respiratory illness which is best
      prevented through vaccination. Currently, all US licensed influenza vaccines are
      produced in embryonated chicken eggs. The Baculovirus Expression Vector System
      (BEVS) technology offers several advantages over existing technology, including
      an exact match between the circulating virus and the antigen in the vaccine,
      speed, safety, versatility, and reliable scale-up. The expresSF+ insect cells are
      grown in the absence of serum and have been extensively qualified for safety
      according to ICH and US FDA guidance and for suitability for the production of
      recombinant proteins using BEVS. FluBlok, a recombinant hemagglutinin influenza
      vaccine, is composed of purified hemagglutinin protein produced using the BEVS
      technology. FluBlok has been shown to be safe, effective, and efficacious in
      human clinical studies.

PMID- 18804388
TI  - The influence of handheld weight on the scapulohumeral rhythm.
AB  - Scapulohumeral rhythm (SHR) provides insight to neuromuscular control and
      fundamental biomechanics of the shoulder. This rhythm often is disrupted in
      pathologic shoulders. As the first step, we sought to quantify SHR in healthy
      subjects for diagnostic assessment of shoulder function. Ten healthy shoulders
      were studied. Three-dimensional models of the humerus and scapula were created
      from computed tomography scans. Dynamic shoulder motion was recorded by use of
      single-plane fluoroscopy during arm abduction with 0-kg and 3-kg handheld loads.
      Shoulder kinematics were quantified by use of model-based 3-dimensional-to-2
      dimensional registration techniques. SHR decreased (more scapular motion) with
      increasing abduction. With a 3-kg load, scapulothoracic motion was significantly
      reduced through the range of 35 degrees to 45 degrees of glenohumeral motion.
      Muscular stabilization of the scapula increased with external loading, as shown
      by decreased SHR during early lifting. Dynamic scapular stabilization provides a
      critical platform for upper extremity activity.

PMID- 18804386
TI  - Role of retinoic acid in the imprinting of gut-homing IgA-secreting cells.
AB  - Antibody-secreting cells (ASCs) lodging in the mucosa of the small intestine are
      derived from activated B cells that are thought to arise in gut-associated
      lymphoid tissues (GALT). Upon leaving the GALT, B cells return to the blood where
      they must express the gut-homing receptors alpha4beta7 and CCR9 in order to
      emigrate into the small bowel. Recent evidence indicates that gut-associated
      dendritic cells (DCs) in GALT induce gut-homing receptors on B cells via a
      mechanism that depends on the vitamin A metabolite retinoic acid (RA). In
      addition, although ASC associated with other mucosal tissues secrete IgA in an RA
      independent fashion, the presence of high levels of RA in intestine and GALT can
      promote B cell class switching to IgA and thus, boost the production of IgA in
      the intestinal mucosa. Here, we discuss the role of RA in the imprinting of gut
      homing ASC and the evidence linking RA with the generation of intestinal IgA
      ASCs.

PMID- 18804389
TI  - Neuro-rescue during carotid stenting.
AB  - This paper deals with the treatment of acute neurological complications that may
      occur during carotid angioplasty with stenting. Endovascular 'neurorescue'
      techniques include mechanical thrombus removal (using retrieval devices,
      aspiration catheters, and wire or balloon fragmentation) and local and intra
      arterial thrombolysis. The treatment of acute thrombosis and dissection during
      carotid artery and stenting will also be discussed. Knowledge of these additional
      skills is essential to increasing the safety of carotid stenting procedures.

PMID- 18804390
TI  - Further validation of the peripheral artery questionnaire: results from a
      peripheral vascular surgery survey in the Netherlands.
AB  - OBJECTIVES: Peripheral arterial disease (PAD) is associated with adverse
      cardiovascular events and can significantly impair patients' health status.
      Recently, marked methodological improvements in the measurement of PAD patients'
      health status have been made. The Peripheral Artery Questionnaire (PAQ) was
      specifically developed for this purpose. We validated a Dutch version of the PAQ
      in a large sample of PAD patients. DESIGN: Cross-sectional study. METHODS: The
      Dutch PAQ was completed by 465 PAD patients (70% men, mean age 65+/-10 years)
      participating in the Euro Heart Survey Programme. Principal components analysis
      and reliability analyses were performed. Convergent validity was documented by
      comparing the PAQ with EQ-5D scales. RESULTS: Three factors were discerned;
      Physical Function, Perceived Disability, and Treatment Satisfaction (factor
      loadings between 0.50 and 0.90). Cronbach's alpha values were excellent (mean
      alpha=0.94). Shared variance of the PAQ domains with EQ-5D scales ranged from 3
      to 50%. CONCLUSIONS: The Dutch PAQ proved to have good measurement qualities;
      assessment of Physical Function, Perceived Disability, and Treatment Satisfaction
      facilitates the monitoring of patients' perceived health in clinical research and
      practice. Measuring disease-specific health status in a reliable way becomes
      essential in times were a wide array of treatment options are available for PAD
      patients.

PMID- 18804391
TI  - Deep Vein Thrombosis after Arterial Surgery: A Literature Review by M. Bani-Hani,
      M. Titi, H. Al-khaffaf.

PMID- 18804392
TI  - Time-trends in vascular access surgery in Sweden 1987-2006.
AB  - OBJECTIVE: To study time-trends in vascular access surgery. DESIGN: Prospectively
      registered data. MATERIAL AND METHODS: The Swedish vascular registry (Swedvasc)
      was searched for haemodialysis access operations (HAO) 1987-2006. RESULTS: 12,342
      open and endovascular operations were identified. Eighty-five percent of HAO 2004
      2006 were reported to the registry. The median age of patients having their first
      HAO increased from 56 to 68 during the first decade (p<0.0001), then remained
      stable. The frequency of diabetes increased from 12% in 1987 to 32% in 2006
      (p<0.0001). The percentage of first HAO of total workload decreased from 76% to
      48%. The percentage of first HAO performed as vein fistulas remained unchanged.
      The number of patients recorded for ten or more previous HAO increased over time.
      Percutaneous angioplasties increased during the last decade. Of 4706 patients
      operated on with primary radiocephalic AV-fistulas, 2933 (62%) were operated only
      once. Analysis of 3739 subsequent operations in 1773 patients disclosed that at
      the tenth operation vein was still used in 54%. With an increasing number of
      operations, arterial inflow shifted towards a more proximal position.
      CONCLUSIONS: Over time, the patients undergoing HAO became older and more often
      diabetic, reoperations increased. Despite these circumstances, vascular surgeons
      perform AV-fistulas without grafts in most patients.

PMID- 18804393
TI  - Peritoneal tuberculosis.

PMID- 18804394
TI  - Malignant lymphoma of the tonsil in a patient with Behcet's disease.
AB  - Several connective tissue diseases such as rheumatoid arthritis and polymyositis
      are associated with cancer. In contrast, cancer is rarely reported in patients
      with Behcet disease. We report a case of lymphoma during the course of Behcet
      disease. Etiopathogenic factors are discussed. A 46-year-old man with a 14-year
      history of Behcet disease was diagnosed with non-Hodgkin malignant lymphoma of
      the right tonsil. He met international criteria for Behcet disease, which
      manifested as refractory oral ulcers requiring dapsone treatment. He achieved a
      complete remission of the lymphoma after three chemotherapy courses and local
      radiation therapy (45 Gy). At last follow-up 4 years later, he was still in
      complete remission.

PMID- 18804396
TI  - [Vaginal or laparoscopic assisted vaginal myomectomy: interest in the double
      way].
AB  - OBJECTIVES: To evaluate vaginal and laparoscopic-assisted vaginal myomectomy in
      order to find interest and indications of this two-way approach of myomectomy.
      PATIENTS AND METHODS: Retrospective study of 60 patients operated of a myomectomy
      by vaginal or laparoscopic-assisted vaginal way between December 1999 and January
      2007. RESULTS: Thirty-three patients (55%) profited from an exclusive vaginal
      myomectomy (group 1) and 27 (45%) from a laparoscopic-assisted vaginal myomectomy
      (group 2). The vaginal gesture in group 2 was carried out mainly because of
      difficult dissections of deep interstitial myomes (60%) or for the closing of
      hysterotomies not accessible by coelioscopic way (40%). Mean operating time,
      blood loss and length of hospital stay were 120 minutes, 431 ml, 3.2 days in
      group 1 and 180 minutes, 437 ml, 5.1 days in group 2, respectively.
      Laparoconversions and notable complications rates were 9% in group 1 and 15% in
      group 2. DISCUSSION AND CONCLUSION: Laparoscopic-assisted vaginal myomectomy is
      interesting to widen indications of laparoscopic way for myomectomy. However,
      considering complications and rate of laparoconversion, it is necessary to define
      situations against indicating this gesture. The methods of prevention of the
      infection also remain to be found.

PMID- 18804397
TI  - [Perinatal management and neurological outcome of newborns hospitalized with
      Rhesus hemolytic disease].
AB  - OBJECTIVES: To evaluate perinatal management and neurological outcome in a group
      of infants born with Rhesus fetomaternal allo-immunization. PATIENTS AND METHODS:
      Between 1 January and 31 December 2005, all newborns admitted to neonatal unit of
      Rouen tertiary centre for Rhesus hemolytic disease were included in a
      retrospective study and divided in two groups. The newborns who were treated with
      intrauterine transfusion are in the group 1 and those who needed only postnatal
      treatment in the group 2. In each case, were considered antenatal management
      (ultrasonographic data, middle cerebral artery peak systolic velocity,
      intrauterine transfusion), postnatal treatment (phototherapy, exchange
      transfusion, transfusion requirements) and neurological outcome. RESULTS: Among
      42 cases of Rhesus allo-immunization observed in six years, 28 newborns (67%)
      were admitted for neonatal cares. No case of fetal hydrops was noted. But 16/28
      (57%) were preterm with a median term of 35 weeks gestation (32-36 weeks). In
      group 1 of six infants who had received intrauterine transfusion (IUT), only one
      (17%) needed postnatal exchange transfusion, and all six received one to three
      blood transfusions after their birth. In group 2 of 22 infants who did not
      receive IUT, 6/22 (27%) needed postnatal exchange and 18/22 (82%) of them
      received one to four blood transfusions. Phototherapy duration and albumin
      requirements were similar in both groups. Three deaths occurred, one due to
      necrotizing enterocolitis and the other two later on due to sudden infant death
      and fulminant meningococcemia. Neurological outcome of the remaining 25 children
      was normal. DISCUSSION AND CONCLUSION: Rhesus alloimmunization remain a situation
      at risk. Neonatal clinical presentation is less severe than previously described
      due to improvement in antenatal management. Infants required less postnatal
      exchange transfusion when they received intrauterine transfusion but more
      frequent blood transfusions.

PMID- 18804398
TI  - Finite element application in implant research for treatment of lumbar
      degenerative disc disease.
AB  - Surgical treatment for disc degeneration can be roughly grouped as fusion, disc
      replacement and dynamic stabilization. The clinical efficacy and biomechanical
      features of the implants used for disc degenerations can be evaluated through
      short- or long-term follow up observation, in vitro and in vivo experiments and
      computational simulations. Finite element models are already making an important
      contribution to our understanding of the spine and its components. Models are
      being used to reveal the biomechanical function of the spine and its behavior
      when healthy, diseased or damaged. They are also providing support in the design
      and application of spinal instrumentation. The article reviewed the most recent
      studies in the application of FE models that address the issue of implant
      research for treatment of low back pain. The published studies were grouped and
      reviewed thoroughly based on the function of implants investigated. The
      considerations of the finite element analysis in these studies were further
      discussed.

PMID- 18804399
TI  - Familial parkinsonism: study of original Sagamihara PARK8 (I2020T) kindred with
      variable clinicopathologic outcomes.
AB  - BACKGROUND: Since the causative gene linked to PARK8 parkinsonism was identified
      as LRRK2, LRRK2 gene mutations have been found to occur in about 4% of patients
      with hereditary Parkinson disease (PD); this percentage is even higher in certain
      populations. Moreover, no clear clinical differences between PARK8-linked
      parkinsonism and sporadic PD have been identified. Neuropathologic findings have
      been diverse in PARK8 parkinsonism, but few of the clinicopathologic examinations
      have been performed in the same family tree. We aimed to describe PET and
      neuropathologic findings in members of the same family tree with PARK8
      parkinsonism. METHODS: We conducted PET of 2 subjects and neuropathologically
      examined 8 subjects in the same family from the Sagamihara district, the original
      source of PARK8-linked parkinsonism (I2020T mutation). RESULTS: The results of
      the PET scans were virtually identical to those seen in sporadic PD. The
      neuropathologic study results showed pure nigral degeneration with no Lewy bodies
      in 6 cases. One case, however, showed the presence of Lewy bodies and was similar
      neuropathologically to conventional PD with Lewy bodies. Another case had
      multiple system atrophy pathology. CONCLUSIONS: Our study of PARK8-linked
      parkinsonism affecting several members of the same pedigree shows that the same
      gene mutation can induce diverse neuropathologies, even if the clinical picture
      and PET findings are virtually identical.

PMID- 18804400
TI  - The validity and intra-tester reliability of a clinical measure of humeral head
      position.
AB  - The purpose of this study was to determine the degree of criterion validity and
      intra-tester reliability of humeral head palpation in subjects with shoulder
      pathology. The study also sought to determine whether there was any effect of arm
      position on humeral head position in subjects with shoulder pathology. In a same
      day repeated measures design, 27 subjects had the distance between the most
      anterior portion of the humeral head and the anterior edge of the acromion
      measured by a radiologist using MRI (supine), and by a physiotherapist using
      palpation and photography (supine, sit with arm in neutral and in abduction). The
      Standard Error of Measurement (SEM) for the difference between MRI and palpation
      ranged from 3.4 to 4.4mm and correlated significantly with palpation measures in
      sit (r=0.57-0.64, p<or=0.002). The Intraclass Correlation Coefficients (ICCs) and
      SEMs for intra-tester reliability were 0.85 and 2.6mm for supine, 0.86 and 2.2mm
      for sit (glenohumeral neutral), and 0.91 and 3.0mm for sit (glenohumeral
      abduction). Significant differences between the positions of sit neutral and sit
      with abduction were found (p<0.001). Humeral head palpation in sit abduction
      demonstrates sufficient validity and reliability for clinical use.

PMID- 18804401
TI  - Global epidemiology of oral and oropharyngeal cancer.
AB  - This review presents data on incidence, mortality, survival and trends in cancers
      of the lip, oral cavity and oropharynx using available recent data sources around
      the world. Oral and pharyngeal cancer, grouped together, is the sixth most common
      cancer in the world. The review focuses primarily on several high-risk countries
      in an attempt to gain insight into the geographic variations in the incidence of
      this cancer in the globe and to relate the high incidence in some populations to
      their life style. With an estimated half a million cases around the globe and the
      rising trends reported in some populations, particularly in the young, urgent
      public health measures are needed to reduce the incidence and mortality of oral
      and oropharyngeal cancer.

PMID- 18804402
TI  - VEGF and ki 67 expression in squamous cell carcinoma of the tongue: An
      immunohistochemical and computerized image analysis study.
AB  - Over-expression of ki 67 and vascular endothelial growth factor (VEGF) is a
      frequent finding in squamous cell carcinoma (SCC) of the oral mucosa. The
      expression of VEGF and ki 67 proteins was studied in a cohort of 87 patients with
      primary, previously untreated SCC of the tongue, using computerized image
      analysis (CIA) in order to determine the potential prognostic significance of
      these factors. Immunohistochemical analysis was performed with monoclonal anti-ki
      67 (MIB 1) and anti-VEGF antibodies. A digital image analysis assay was applied
      for the evaluation of the results. Using CIA, VEGF over-expression was observed
      in 24/87 (27.5%) of the examined cases and this finding correlated to the stage
      of the disease (p=0.05). ki 67 was over-expressed in 49/87 (56.3%) of the cases
      and correlated to the size of the tumors (p=0.05). Cox regression analysis showed
      that there was no prognostic significance associating VEGF protein expression to
      survival status of the examined patients (p=0.77), whereas ki 67 over-expression
      was strongly correlated to poor prognosis (p=0.017). The size of the primary
      tumors was also strongly correlated to survival status of the patients (p=0.024),
      whereas stage of disease showed a borderline statistical significance (p=0.091).

PMID- 18804403
TI  - Bag-1 proteins in oral squamous cell carcinoma.
AB  - Bag-1 is an anti-apoptotic protein that exhibits altered expression in many
      malignancies, including oral squamous cell carcinoma. The bag-1 gene gives rise
      to different protein products with different subcellular localisations through
      alternative translational initiation sites. In oral squamous cell carcinoma,
      cytoplasmic expression has been associated with metastasis to regional lymph
      nodes and poor prognosis. In contrast, the longest Bag-1 isoform is nuclear and
      may regulate differentiation in oral epithelium. In this review, the functions of
      the three isoforms of Bag-1 expressed in oral epithelial cells are discussed in
      relation to their contribution to oral carcinogenesis.

PMID- 18804404
TI  - Utility of combined (18)F-fluorodeoxyglucose-positron emission tomography and
      computed tomography in patients with cervical metastases from unknown primary
      tumors.
AB  - (18)F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) has been
      reported to identify primary tumors in patients with cervical metastases from
      cancer of unknown primary (CUP). However, few reports have assessed the use of
      combined FDG-PET/computed tomography (CT) in this setting. We therefore examined
      the utility of combined FDG-PET/CT in the detection of primary tumors and
      unrecognized metastases in these patients. Patients with previously untreated
      CUPs underwent head and neck CT and whole-body FDG-PET/CT before panendoscopy and
      guided biopsy. The diagnostic accuracy of CT and FDG-PET/CT in detecting primary
      tumors and cervical metastases was compared with that of histopathology. The
      ability of FDG-PET/CT to detect distant metastases was also tested. Of the 44
      eligible patients, 16 had occult primary tumors in the head and neck. FDG-PET/CT
      was significantly more sensitive than CT for detecting primary tumors (87.5% vs.
      43.7%, P=.016), but their specificity did not differ (82.1% vs. 89.3%, P=.500).
      Thirty-four of 44 patients underwent neck dissection; 67 of 182 dissected
      cervical levels had metastatic nodal diseases. On a level-by-level basis, FDG
      PET/CT was significantly more sensitive than CT (94.0% vs. 71.6%, P<.001), but
      the two methods were equally specific (94.8% vs. 96.5%). FDG-PET/CT correctly
      detected distant metastases in 6 of 6 patients. Combined FDG-PET/CT is a useful
      screening method for primary tumor detection, accurate nodal staging, and distant
      metastases in patients with CUPs.

PMID- 18804405
TI  - Ribonucleotide reductase small subunit p53R2 promotes oral cancer invasion via
      the E-cadherin/beta-catenin pathway.
AB  - The p53-inducible p53R2 gene has been isolated and shown to play a crucial role
      in DNA repair and synthesis after DNA damage. Moreover, the expression and
      activity of p53R2 has been reported to be associated with the anticancer agent
      resistance of human cancer cells. Previously, we reported that the presence of
      p53R2 expression was a predictive factor for regional lymph node metastasis in
      oral squamous cell carcinoma; however, the mechanism of cancer metastasis by
      p53R2 expression is still unclear. In the present study, we analyzed the
      correlation of p53R2 expression with cancer invasion in vitro. Three human oral
      cancer cell lines (SAS, HSC-3 and Ca9-22) were cultured, and the invasive
      potential of these cancer cells was evaluated using Matrigel invasion assay. To
      investigate the effect of p53R2 on cancer invasion, the down-regulation of p53R2
      was examined by small interfering RNA (siRNA). Moreover, we examined the
      intracellular localization of cell adhesion molecules (E-cadherin and beta
      catenin) in subcellular extractions of cancer cells by immunoblotting. The
      proteolytic activity of matrix metalloproteinases (MMPs) was assessed by gelatin
      zymography. Down-regulation of p53R2 significantly enhanced the invasion
      potential (p<0.01), and enhanced nuclear translocation of beta-catenin with loss
      of total cellular E-cadherin expression in p53 mutant cancer cells, but not in
      p53 wild-type cancer cells. These changes in the invasion index by p53R2 siRNA
      transfection were not accompanied by alterations in MMP activity and expression.
      These results suggested that the expression of p53R2 could be associated with the
      invasion of cancer cells, and indicated that p53R2 might promote cancer invasion
      via the E-cadherin/beta-catenin pathway without the alteration of MMP activity.

PMID- 18804406
TI  - Expression of osteopontin and its receptors in ameloblastomas.
AB  - This study used an immunohistochemical method to examine the expression of
      osteopontin (OPN) in 30 ameloblastomas and of integrin alpha(v) and CD44v6 in 20
      of these 30 ameloblastomas. We found that the positive staining rate in
      ameloblastomas was 87% for OPN, 45% for integrin alpha(v), and 90% for CD44v6.
      Both ameloblast-like and stellate reticulum-like cells showed a high expression
      of OPN and CD44v6. There was also a strong integrin alpha(v) immunostaining on
      the cell membrane of osteoclasts. Binding of OPN to osteoclast cell membrane
      receptor integrin alpha(v) can activate the osteoclast and increase its
      osteolytic activity. In addition, binding of OPN to ameloblastoma tumor cell
      membrane receptor CD44v6 can enhance tumor cell migration, invasion and spread.
      Therefore, we suggest that the local aggressive behavior and high osteolytic
      ability of ameloblastomas in the jawbones can be explained by the high expression
      of OPN and CD44v6 in ameloblastoma cells and the high expression of integrin
      alpha(v) in osteoclasts.

PMID- 18804407
TI  - FDG-PET predicts survival and distant metastasis in oral squamous cell carcinoma.
AB  - High [(18)F]-2-fluorodeoxyglucose (FDG)-uptake of primary tumor, assessed by
      pretreatment positron emission tomography (PET), shows poor overall survival of
      patients after several therapies in various cancers. An association between FDG
      uptake and distant metastasis-free survival in oral squamous cell carcinoma
      (OSCC) has not been assessed so far. An objective of this study is to investigate
      an association between FDG-uptake and overall survival of OSCC patients, and to
      ask whether FDG-uptake is related with distant metastasis-free survival in OSCC.
      Twenty-four patients who underwent both pretreatment FDG-PET and radical surgery
      without preoperative therapy were enrolled. We used the maximum standardized
      uptake value (SUVmax) as FDG-uptake. Overall survival, locoregional recurrence
      free survival and distant metastasis-free survival were analyzed by Kaplan-Meier
      method. In univariate survival analysis, patients with SUVmax>or=12 exhibited
      significance in both shorter 3-year overall survival (p<0.01) and distant
      metastasis-free survival (p<0.04) than patients with SUVmax<12. Moreover, by Cox
      proportional hazards model of multivariate analysis, SUVmax>or=12 was found to be
      independent of clinical T and N categories, and exhibited significance in both
      shorter 3-year overall survival (p<0.02) and distant metastasis- free survival
      (p<0.05) than patients with SUVmax<12. These results suggest that pretreatment
      FDG-PET is able to provide both non-invasive and effective information for
      identifying a high- or low-risk group of OSCC patients with distant metastasis.

PMID- 18804408
TI  - Unknown primary head and neck cancer treated with intensity-modulated radiation
      therapy: to what extent the volume should be irradiated.
AB  - To evaluate the efficacy and feasibility of irradiation with intensity-modulated
      radiotherapy (IMRT) technique in patients with head and neck carcinoma of unknown
      primary (HNCUP). Between February 2000 and November 2006, 22 consecutive patients
      diagnosed with HNCUP were treated with IMRT. Of these, four patients were
      excluded because two of them underwent IMRT only as a boost and the other two had
      distant metastasis at presentation and were treated palliatively. Of the
      remaining 18 patients eligible for analysis, 6 had definitive IMRT and 12 had
      postoperative IMRT (8 with neck dissection and 4 with excisional biopsy). One
      patient with abnormal lymph node found unexpectedly during carotid endarterectomy
      was treated to ipsilateral neck only. The target volumes for the other 17
      patients include nasopharynx, oropharynx, retropharyngeal lymph nodes, and
      bilateral neck. In 1 patient who had extensive lymph node involvement, the
      hypopharynx and the larynx were defined as target. In all other patients the
      larynx including hypopharynx were defined as dose-limiting structures. The
      parotids, cervical esophagus, spinal cord, brain stem, optic nerves and the
      orbits are also outlined as dose-limiting structures. All patients completed
      their treatment without interruption and severe complications. With a median
      follow-up time of 25.5 months, 2 patients had persistent cervical lymphadenopathy
      and 2 had distant metastases. Another patient developed a lung cancer and a
      second pyriform sinus cancer 25 months after treatment. The 2-year overall
      survival, regional recurrence-free survival and distant metastases-free survival
      were 74.2%, 88.5%, and 88.2%, respectively. Six patients had prophylactic
      percutaneous endoscopic gastrostomy (PEG) tubes placed before radiation. Most had
      PEG tubes removed within 7 months after the completion of treatment. IMRT
      delivered to comprehensive bilateral neck and putative mucosal site (including
      nasopharynx, oropharynx, and retropharyngeal lymph nodes) appears to be effective
      for patients with HNCUP. Our preliminary results show that such approach does not
      compromise local-regional control. Further studies with more patients and longer
      follow-up are necessary to validate this approach.

PMID- 18804409
TI  - End of life considerations in the head and neck cancer patient.
AB  - Oral and head and neck cancer carries an associated death rate five years after
      diagnosis and treatment that is high, essentially at a 50% level. In association
      with the dying process and the transition to death is a wide array of issues and
      considerations including the physical and emotional needs of the patient as well
      as associated caregivers. At a point, the transition must be understood in terms
      of non-oncologic management considerations and the broader needs of the patient
      and their family and the caregivers. Psychosocial and spiritual needs are to be
      addressed as well as the necessary components of preparation for death as to make
      a "good death". Communicating the status of the terminally-ill patient to the
      patient themselves and their family when cure or remission is no longer possible
      and the consideration of hospice care, palliation and issues of grieving all
      contribute to considerations in overall management at the end of life.

PMID- 18804410
TI  - Cetuximab in recurrent and/or metastatic salivary gland carcinomas: A phase II
      study.
AB  - EGFR overexpression in salivary gland carcinomas provides the rational for the
      investigation of anti-EGFR treatments in recurrent and/or metastatic salivary
      gland cancers (RMSGCs). The activity of cetuximab in terms of clinical benefit
      rate (CBR) defined as the occurrence of objective response (CR or PR) or stable
      disease (SD) for >or=6months was investigated. From April to December 2005, 30
      patients [23 adenoid cystic carcinoma (ACC) and 7 non-ACC] were treated with
      cetuximab at 400mg/m(2)/week followed by 250mg/m(2)/week until progression, major
      toxicity or voluntary discontinuation. EGFR expression and gene status were
      retrospectively analyzed by immunocytochemistry and fluorescence in situ
      hybridization, respectively. A median of 14 courses of cetuximab (range 5-54)
      were infused. Skin toxicity was the main adverse event. Cetuximab provides a CBR
      in 50% (95% CL, 31 to 69%) of cases. None tumor sample showed EGFR gene
      amplification and an increased EGFR copy number was observed in 12% of samples,
      all ACC. Skin rash >or=G2, EGFR overexpression and EGFR copy number were not
      statistically correlated to CB. In RMSGCs further evaluations of EGFR targeting
      agents are advisable and should take place by appropriate tumor biological
      selection, differentiating ACC from non-ACC.

PMID- 18804411
TI  - MDM2 SNP309 does not confer an increased risk to oral squamous cell carcinoma but
      may modulate the age of disease onset.
AB  - The MDM2 SNP309 has been associated with increased expression of the protein
      which could suppress p53 function, and has been shown to modulate risk to cancer.
      We have previously shown that overexpression of MDM2 is a common event in oral
      cancers. In the present study, we determined the association between the MDM2
      SNP309 polymorphism and oral cancer in 207 oral cancer patients and 116 normal
      subjects. We genotyped the MDM2 SNP309 by PCR-RFLP. Logistic regression was
      adapted to calculate odds ratios for MDM2 SNP309 polymorphism from univariate and
      multivariable adjusted models. Our results suggest that MDM2 SNP309 does not
      confer increased risk to oral cancer (OR=1.55, 95% CI=0.77-3.11). However, the
      GG/TG genotype was associated with later disease onset in women above 55 years of
      age. Collectively, our data suggests that MDM2 SNP309 may modulate the risk to
      oral cancer and is a modifier of the age at oral cancer onset in women above the
      age of 55 years.

PMID- 18804412
TI  - Oral cancer prevention and control--the approach of the World Health
      Organization.
AB  - Cancer is one of the most common causes of morbidity and mortality today. It is
      estimated that around 43% of cancer deaths are due to tobacco use, unhealthy
      diets, alcohol consumption, inactive lifestyles and infection. Low-income and
      disadvantaged groups are generally more exposed to avoidable risk factors such as
      environmental carcinogens, alcohol, infectious agents, and tobacco use. These
      groups also have less access to the health services and health education that
      would empower them to make decisions to protect and improve their own health. Oro
      pharyngeal cancer is significant component of the global burden of cancer.
      Tobacco and alcohol are regarded as the major risk factors for oral cancer. The
      population-attributable risks of smoking and alcohol consumption have been
      estimated to 80% for males, 61% for females, and 74% overall. The evidence that
      smokeless tobacco causes oral cancer was confirmed recently by the International
      Agency for Research on Cancer. Studies have shown that heavy intake of alcoholic
      beverages is associated with nutrient deficiency, which appears to contribute
      independently to oral carcinogenesis. Oral cancer is preventable through risk
      factors intervention. Prevention of HIV infection will also reduce the incidence
      of HIV/AIDS-related cancers such as Kaposi sarcoma and lymphoma. The WHO Global
      Oral Health Programme is committed to work for country capacity building in oral
      cancer prevention, inter-country exchange of information and experiences from
      integrated approaches in prevention and health promotion, and the development of
      global surveillance systems for oral cancer and risk factors. The WHO Global Oral
      Health Programme has established a global surveillance system of oral cavity
      cancer in order to assess risk factors and to help the planning of effective
      national intervention programmes. Epidemiological data on oral cancer (ICD-10:
      C00-C08) incidence and mortality are stored in the Global Oral Health Data Bank.
      In 2007, the World Health Assembly (WHA) passed a resolution on oral health for
      the first time in 25 years, which also considers oral cancer prevention. The
      resolution WHA60 A16 URGES Member states--To take steps to ensure that prevention
      of oral cancer is an integral part of national cancer-control programmes, and to
      involve oral-health professionals or primary health care personnel with relevant
      training in oral health in detection, early diagnosis and treatment;--The WHO
      Global Oral Health Programme will use this statement as the lead for its work for
      oral cancer control www.who.int/oral_health.

PMID- 18804413
TI  - Intensity-modulated radiation therapy for oropharyngeal cancer: radiation dosage
      constraint at the anterior mandible.
AB  - Because the survival of endosseous implants in irradiated bone is lower than in
      non-irradiated bone, particularly if the irradiation dose exceeds 50Gy, a study
      was carried out to assess the irradiation dose in the anterior mandible, when
      intensity modulated radiation therapy (IMRT) is used. The hypothesis was that
      adequate IMRT planning in oropharyngeal cancer patients is allowing sufficiently
      low anterior mandibular bone radiation dosages to safely insert endosseous
      implants. Ten randomly selected patients with oropharyngeal cancer, primarily
      treated by intensity-modulated radiotherapy (IMRT), were included in this study.
      First, at five determined positions distributed over the anterior mandible, the
      appropriate radiation dosages were calculated according to the originally
      arranged fractionated radiation schedule. Second, for each patient an adjusted
      fractionated radiation schedule was established with an extra dose constraint
      which allowed a lower dose in the mandible taking into account that the anterior
      mandible needs protection against radiation-induced osteoradionecrosis. The goal
      for the adjusted fractionated radiation schedule was similar as that of the
      original fractionated radiation schedule, including a desired tumour target
      dosage of 70Gy and maximum mean local dosages for organs at risk. The data
      revealed a considerable and statistically significant, irradiation dose reduction
      in the anterior mandible without compromising the other constraints. As a result
      of this study it is strongly advised to maximize dose constraint to the anterior
      mandible when planning irradiation for oropharyngeal cancer patients, using IMRT.
      This would greatly facilitate successful implant treatment for this group of
      patients. The fractionated radiation schedules used, should also be used for the
      planning of the best implant positions by integrating them in the implant
      planning software.

PMID- 18804414
TI  - p16(CDKN2A) expression during rat tongue carcinogenesis induced by 4
      nitroquinoline-1-oxide.
AB  - p16(CDKN2A) is one of the most important tumor-suppressor genes and has been
      investigated widely in recent years for its role in oral carcinogenesis, but few
      have explored the relationship between its RNA and protein, especially in
      precancerous tissues. The aim of this study was to explore the relationship of
      mRNA and protein level of p16(CDKN2A) in rat tongue carcinogenesis process
      induced by 4-nitroquinoline-1-oxide. By the use of semi-quantitative RT-PCR,
      immunohistochemistry (IHC) and Western Blot, histologically normal, premalignant
      and invasive squamous cell carcinoma samples from the animal model were explored
      respectively. The results showed the levels of mRNA of p16(CDKN2A) did not
      significantly change during the carcinogenesis process when compared with
      controls. However, detectable level of P16 protein expression was lost in both
      the dysplasia and carcinoma groups. We could conclude that p16(CDKN2A) in 4NQO
      induced rat tongue carcinogenesis might be inactivated predominantly by
      posttranscriptional regulation.

PMID- 18804415
TI  - Rhein inhibits invasion and migration of human nasopharyngeal carcinoma cells in
      vitro by down-regulation of matrix metalloproteinases-9 and vascular endothelial
      growth factor.
AB  - Progression of cancer invasion is believed to be dependent on the remodeling of
      extracellular matrix induced by tumor cells. Rhein has been shown to inhibit the
      growth and proliferation of human nasopharyngeal carcinoma (NPC) cells. However,
      the molecular mechanism underlying rhein-induced inhibition of cancer invasion
      has not been explored. Herein, we show that rhein could inhibit the invasion and
      migration of NPC cells in vitro. Rhein inhibits invasion by reducing the
      expression of matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth
      factor (VEGF). Moreover, we demonstrate that the pathway involved in rhein
      inhibited invasion is presumably through the growth factor receptor bound protein
      2/son of sevenless-Ras-mitogen-activated protein kinase (GRB2/SOS-Ras-MAPK)
      pathway, as shown by an decrease in the expression levels of GRB2, SOS-1 and Ras
      as well as led to suppression of the phosphorylation of extracellular signal
      regulated kinase (ERK) and p38 MAPK. Further study has shown that rhein also
      inhibited activation of transcription factor nuclear factor kappaB (NF-kappaB),
      which is known to implicate the regulation of MMP-9 and VEGF gene expression in
      cancer invasion. Our findings suggest that rhein inhibits the invasion of NPC
      cells may be mediated in part through the suppression of MMP-9 and VEGF
      expression via the modulation of NF-kappaB signaling pathway.

PMID- 18804416
TI  - Urinary neutrophil gelatinase associated lipocalin (NGAL), a marker of tubular
      damage, is increased in patients with chronic heart failure.
AB  - Renal impairment, as measured by reduced glomerular filtration rate (GFR) and
      increased urinary albumin excretion (UAE), is prevalent in patients with chronic
      heart failure (CHF) and is associated with reduced survival. The prevalence of
      structural tubular damage in CHF is unknown. We investigated 90 CHF patients and
      20 age and sex matched healthy controls, and determined estimated GFR, UAE, N
      terminal-pro brain natriuretic peptide (NT-proBNP) and urinary neutrophil
      gelatinase associated lipocalin (NGAL) as a marker for tubular damage. CHF
      patients had significantly lower averaged estimated GFR (64+/-17 vs 90+/-12
      mL/min/1.73 m(2), P<0.0001), but higher NT-proBNP and UAE levels (both P<0.0001).
      Median urinary NGAL levels were markedly increased in CHF patients compared to
      controls (175 (70-346) vs 37 (6-58) microg/gCr, P<0.0001). Both serum creatinine
      (r=0.26, P=0.006) and eGFR (r=-0.29, P=0.002) were significantly associated with
      urinary NGAL levels as were NT-proBNP and UAE but to a lesser extent. In
      conclusion, renal impairment in CHF patients is not only characterised by
      decreased eGFR and increased UAE, but also by the presence of tubular damage, as
      measured by increased urinary NGAL concentrations.

PMID- 18804417
TI  - The emission potential of different land use patterns for the occurrence of
      coliphages in surface water.
AB  - Different land use patterns were investigated for their potential as non-point
      sources of coliphage emissions into surface waters. Water samples were taken
      regularly at five locations in the upper reaches of the river Swist, Germany.
      Samples of surface and subsurface run-off were taken within the same catchment
      area after rainfall events using a newly developed device that made it possible
      to collect current concentrations of the effluent compounds. The water quality
      was examined for the occurrence of somatic coliphages and F(+)-specific RNA
      bacteriophages as well as for various bacteria over the period of a hydrological
      year. The potential of various bacteria as indicators for the occurrence of
      phages was evaluated using statistical correlations. The load of coliphages
      varied depending on the land use type, but it did not differ as much as the
      bacterial parameters. River sections in intensively used areas turned out to be
      more contaminated than in less intensively used regions. The concentrations of
      phages from surface and subsurface run-off in most samples were quite low for all
      land use types and did not show conspicuous variations of surface and subsurface
      run-off within one land use type. Therefore, high concentrations of phages in
      river water cannot be explained only by non-point effluent from open ground.
      Following consideration of the statistical results, conventional indicator
      bacteria seem not to be reliable indicator organisms for coliphages and
      subsequently for human pathogen viruses. The detected concentrations of
      coliphages in several water samples of river sections surrounded by intensively
      used areas underpin an existing health risk in the use of river water for e.g.
      recreational activities or irrigation.

PMID- 18804418
TI  - Assessment of somatic k-RAS mutations as a mechanism associated with resistance
      to EGFR-targeted agents: a systematic review and meta-analysis of studies in
      advanced non-small-cell lung cancer and metastatic colorectal cancer.
AB  - BACKGROUND: Somatic mutations of the k-RAS oncogene have been assessed as a
      mechanism of de-novo resistance to epidermal growth factor receptor (EGFR)
      tyrosine-kinase inhibition in patients with non-small-cell lung cancer (NSCLC),
      and to anti-EGFR monoclonal antibodies in patients with metastatic colorectal
      cancer (mCRC). The aim of this systematic review and meta-analysis was to assess
      if k-RAS mutations represent a candidate predictive biomarker for anti-EGFR
      targeted therapeutic strategies in mCRC and NSCLC. METHODS: We systematically
      identified articles pertaining to k-RAS mutational status in patients with NSCLC
      treated with tyrosine-kinase inhibitors (TKI), and patients with mCRC treated
      with any anti-EGFR-based regimens. Eligible studies had to report complete
      responses (CR) and partial responses (PR), stratified by k-RAS mutational status.
      Potential between-study heterogeneity was accommodated by use of random-effects
      models for bivariable meta-analysis of sensitivity and specificity (the primary
      endpoints). The positive and negative likelihood ratios (+LR and -LR,
      respectively) of k-RAS mutations for predicting an absence of response were
      considered as secondary endpoints and were calculated by use of pooled estimates
      for sensitivity and specificity. FINDINGS: Of 252 retrieved manuscripts, 17 were
      deemed eligible for the NSCLC meta-analysis (165 of 1008 patients with mutated k
      RAS). The presence of k-RAS mutations was significantly associated with an
      absence of response to TKIs (sensitivity=0.21 [95% CI 0.16-0.28],
      specificity=0.94 [0.89-0.97]; +LR=3.52; -LR=0.84). Of 68 retrieved manuscripts
      reporting on anti-EGFR monoclonal-antibody-based treatment of mCRC, eight studies
      were deemed eligible for the final analysis (306 of 817 patients with mutated k
      RAS). The presence of k-RAS mutations was significantly associated with an
      absence of response to anti-EGFR monoclonal-antibody-based treatments
      (sensitivity=0.47 [0.43-0.52]; specificity=0.93 [0.83-0.97]; +LR=6.82; -LR=0.57).
      INTERPRETATION: This analysis provides empirical evidence that k-RAS mutations
      are highly specific negative predictors of response (de-novo resistance) to
      single-agent EGFR TKIs in advanced NSCLC; and similarly to anti-EGFR monoclonal
      antibodies alone or in combination with chemotherapy in patients with mCRC. The
      low sensitivity and relatively high -LR of k-RAS mutations for determining non
      responsiveness clearly shows that additional mechanisms of resistance to EGFR
      inhibitors exist.

PMID- 18804419
TI  - Computational method for inferring objective function of glycerol metabolism in
      Klebsiella pneumoniae.
AB  - Flux balance analysis (FBA) is an effective tool in the analysis of metabolic
      network. It can predict the flux distribution of engineered cells, whereas the
      accurate prediction depends on the reasonable objective function. In this work,
      we propose two nonlinear bilevel programming models on anaerobic glycerol
      metabolism in Klebsiella pneumoniae (K. pneumoniae) for 1,3-propanediol (1,3-PD)
      production. One intends to infer the metabolic objective function, and the other
      is to analyze the robustness of the objective function. In view of the models'
      characteristic an improved genetic algorithm is constructed to solve them, where
      some techniques are adopted to guarantee all chromosomes are feasible and move
      quickly towards the global optimal solution. Numerical results reveal some
      interesting conclusions, e.g., biomass production is the main force to drive K.
      pneumoniae metabolism, and the objective functions, which are obtained in term of
      several different groups of flux distributions, are similar.

PMID- 18804420
TI  - Translation of genomics research at the bedside: the promise and the challenge.

PMID- 18804421
TI  - Microinjection of urocortin into the rat nucleus tractus solitarii decreases
      arterial blood pressure.
AB  - Systemic administration of urocortin I (Ucn I), a member of the corticotrophin
      releasing factor (CRF) peptide family, modulates cardiovascular system. In the
      central nervous system, Ucn I is found in the nucleus tractus solitarii (NTS),
      which plays an important role in regulating arterial blood pressure (ABP) and
      heart rate (HR) in response to activation of the baroreceptor afferents. In this
      study, we examined the effects of Ucn I, which has a high affinity for both type
      1 and type 2 CRF receptors (i.e. CRF-R1 and -R2), on cardiovascular functions at
      the level of the NTS. A specific agonist of CRF-R1 (i.e. CRF) and a specific
      agonist of CRF-R2 (i.e. Urocortin II) were also tested to identify the specific
      cardiovascular effects induced by individual activation of either CRF-R1 or -R2.
      We found that Ucn I microinjected into the rat NTS produced a significant
      reduction in both ABP and HR. Both agonists for CRF-R1 and -R2 microinjected into
      the NTS also reduced ABP and HR. Our results suggest that Ucn I in the NTS may
      play an important role in cardiovascular regulation and the cardiovascular
      effects of Ucn I may be mediated by activation of both CRF-R1 and -R2, which are
      known to be present in the NTS.

PMID- 18804422
TI  - Hepatolithiasis in a patient with autosomal dominant polycystic kidney disease
      treated by extracorporeal shock wave lithotripsy (ESWL).

PMID- 18804423
TI  - Native protein-initiated ATRP: a viable and potentially superior alternative to
      PEGylation for stabilizing biologics.
AB  - Comparison of in vitro serum stability and enzyme activity retention for
      PEGylated chymotrypsin and structurally different, biocompatible vinyl polymer
      grafts of chymotrypsin was performed. These polymer grafts were synthesized by
      atom transfer radical polymerization (ATRP) initiated by chymotrypsin covalently
      modified with 2-bromoisobutyric acid, the ATRP initiator. The maximum number of
      ATRP initiators attached to chymotrypsin was adjusted to be as close as possible
      to the maximum number of polyethylene glycol chains attached to chymotrypsin for
      better comparison and then polymerizations were conducted. In mouse serum, native
      and PEGylated chymotrypsin deactivated within 24h, whereas chymotrypsin-graft
      poly(N-2-hydroxypropylmethacrylamide) retained >50% of its catalytic activity
      even after 5 days of incubation. In human serum, PEGylated chymotrypsin
      deactivated within 4 days of incubation, whereas native chymotrypsin and
      chymotrypsin-graft-poly(N-2-hydroxypropylmethacrylamide) and chymotrypsin-graft
      poly(2-methacryloyloxyethyl phosphorylcholine) retained >25% catalytic activity
      after 5 days of incubation. Biocompatible vinyl polymer grafts of chymotrypsin
      synthesized by protein-initiated ATRP had higher catalytic activity retention and
      molecular weights and lower polydispersity than PEGylated chymotrypsin. In
      summary, studying the effects of structures of conjugated polymers on the
      stability and activity retention of modified proteins can lead to identification
      of a polymer-protein conjugate having superior pharmacological properties than
      conventionally PEGylated protein. Also, since vinyl monomers that form
      biocompatible polymers are easily polymerizable by ATRP, protein-initiated ATRP
      can become a viable and potentially superior alternative to PEGylation for
      stabilizing biologics.

PMID- 18804424
TI  - Report on EQUATOR Network launch meeting 26th June 2008 "Achieving Transparency
      in Reporting Health Research".

PMID- 18804425
TI  - The compliance of plastic surgeons in the UK with the national guidelines for
      primary cutaneous squamous cell carcinoma.

PMID- 18804426
TI  - Sall4 regulates distinct transcription circuitries in different blastocyst
      derived stem cell lineages.
AB  - Stem cells self-renew or differentiate under the governance of a stem-cell
      specific transcriptional program, with each transcription factor orchestrating
      the activities of a particular set of genes. Here we demonstrate that a single
      transcription factor is able to regulate distinct core circuitries in two
      different blastocyst-derived stem cell lines, embryonic stem cells (ESCs) and
      extraembryonic endoderm (XEN) cells. The transcription factor Sall4 is required
      for early embryonic development and for ESC pluripotency. Sall4 is also expressed
      in XEN cells, and depletion of Sall4 disrupts self-renewal and induces
      differentiation. Genome-wide analysis reveals that Sall4 is regulating different
      gene sets in ESCs and XEN cells, and depletion of Sall4 targets in the respective
      cell types induces differentiation. With Oct4, Sox2, and Nanog, Sall4 forms a
      crucial interconnected autoregulatory network in ESCs. In XEN cells, Sall4
      regulates the key XEN lineage-associated genes Gata4, Gata6, Sox7, and Sox17. Our
      findings demonstrate how Sall4 functions as an essential stemness factor for two
      different stem cell lines.

PMID- 18804427
TI  - Probing meiotic recombination decisions.
AB  - Meiotic recombination promotes genetic variation by mixing parental alleles. Two
      recent studies, one in this issue of Developmental Cell, have applied microarray
      based methods that allow analysis of nearly all of the recombination events
      occurring in a single meiosis. These data provide insights into the molecular
      "decisions" that control the outcome of the recombination process.

PMID- 18804428
TI  - WASp identity theft by a bacterial effector.
AB  - EspF(U), a protein secreted by pathogenic enterohaemorrhagic E. coli (EHEC),
      activates N-WASp/WASp to induce actin pedestal formation in host cells. Two
      recent papers in Nature show that EspF(U) exploits a WASp activation strategy so
      extreme that it may effectively sequester WASp, blinding it to both
      autoinhibition and cellular regulation.

PMID- 18804429
TI  - FGF signaling preserves the integrity of endothelial adherens junctions.
AB  - Fibroblast growth factor (FGF)-activated signaling regulates an array of cellular
      processes ranging from embryonic development to tissue repair. A recent paper by
      Murakami et al. identifies a potentially important role for FGF signaling in
      maintenance of endothelial barrier homeostasis through the regulation of adherens
      junctions.

PMID- 18804430
TI  - Strigolactones and shoot branching: a new trick for a young dog.
AB  - Strigolactones secreted by plant roots are exploited by parasitic plants as
      germination triggers, making their synthesis and signaling important targets for
      crop protection. Meanwhile, genetic analyses have identified several genes
      required for the synthesis and signaling of an unknown shoot branching inhibitor.
      Two recent papers unite these two fields, showing that strigolactones control
      shoot branching.

PMID- 18804431
TI  - Endoplasmic reticulum stress, PrP trafficking, and neurodegeneration.
AB  - In this issue of Developmental Cell, Rane et al. report a cellular pathway to
      link PrP(Sc), via ER stress and the activation of a preemptive quality control
      process, to neurodegeneration in a PrP-dependent manner. This pathway puts
      together several pieces in the puzzle of the relationship between PrP(Sc) and
      brain damage and may in part explain the mechanism of prion neurodegeneration.

PMID- 18804432
TI  - Mitochondrial dynamics and apoptosis: a painful separation.
AB  - Reporting in Molecular Cell, Sheridan et al. (2008) and Breckenridge et al.
      (2008) show that mitochondrial fragmentation is not required to induce cell
      death. Meanwhile, Yamaguchi et al. show that proapoptotic Bcl-2 family members
      promote cytochrome c mobilization through Opa1-mediated cristae remodeling.
      Therefore, the connection between mitochondrial structure and apoptosis is more
      complex than previously imagined.

PMID- 18804434
TI  - Reduced translocation of nascent prion protein during ER stress contributes to
      neurodegeneration.
AB  - During acute stress in the endoplasmic reticulum (ER), mammalian prion protein
      (PrP) is temporarily prevented from translocation into the ER and instead routed
      directly for cytosolic degradation. This "pre-emptive" quality control (pQC)
      system benefits cells by minimizing PrP aggregation in the secretory pathway
      during ER stress. However, the potential toxicity of cytosolic PrP raised the
      possibility that persistent pQC of PrP contributes to neurodegeneration in prion
      diseases. Here, we find evidence of ER stress and decreased translocation of
      nascent PrP during prion infection. Transgenic mice expressing a PrP variant with
      reduced translocation at levels expected during ER stress was sufficient to cause
      several mild age-dependent clinical and histological manifestations of PrP
      mediated neurodegeneration. Thus, an ordinarily adaptive quality-control pathway
      can be contextually detrimental over long time periods. We propose that one
      mechanism of prion-mediated neurodegeneration involves an indirect ER stress
      dependent effect on nascent PrP biosynthesis and metabolism.

PMID- 18804433
TI  - The role of autophagy in mammalian development: cell makeover rather than cell
      death.
AB  - Autophagy is important for the degradation of bulk cytoplasm, long-lived
      proteins, and entire organelles. In lower eukaryotes, autophagy functions as a
      cell death mechanism or as a stress response during development. However,
      autophagy's significance in vertebrate development, and the role (if any) of
      vertebrate-specific factors in its regulation, remains unexplained. Through
      careful analysis of the current autophagy gene mutant mouse models, we propose
      that in mammals, autophagy may be involved in specific cytosolic rearrangements
      needed for proliferation, death, and differentiation during embryogenesis and
      postnatal development. Thus, autophagy is a process of cytosolic "renovation,"
      crucial in cell fate decisions.

PMID- 18804435
TI  - Integrin trafficking regulated by Rab21 is necessary for cytokinesis.
AB  - Adherent cells undergo remarkable changes in shape during cell division. However,
      the functional interplay between cell adhesion turnover and the mitotic machinery
      is poorly understood. The endo/exocytic trafficking of integrins is regulated by
      the small GTPase Rab21, which associates with several integrin alpha subunits.
      Here, we show that targeted trafficking of integrins to and from the cleavage
      furrow is required for successful cytokinesis, and that this is regulated by
      Rab21. Rab21 activity, integrin-Rab21 association, and integrin endocytosis are
      all necessary for normal cytokinesis, which becomes impaired when integrin
      mediated adhesion at the cleavage furrow fails. We also describe a chromosomal
      deletion and loss of Rab21 gene expression in human cancer, which leads to the
      accumulation of multinucleate cells. Importantly, reintroduction of Rab21 rescued
      this phenotype. In conclusion, Rab21-regulated integrin trafficking is essential
      for normal cell division, and its defects may contribute to multinucleation and
      genomic instability, which are hallmarks of cancer.

PMID- 18804436
TI  - Polar body emission requires a RhoA contractile ring and Cdc42-mediated membrane
      protrusion.
AB  - Vertebrate oocyte maturation is an extreme form of asymmetric cell division,
      producing a mature egg alongside a diminutive polar body. Critical to this
      process is the attachment of one spindle pole to the oocyte cortex prior to
      anaphase. We report here that asymmetric spindle pole attachment and anaphase
      initiation are required for localized cortical activation of Cdc42, which in turn
      defines the surface of the impending polar body. The Cdc42 activity zone overlaps
      with dynamic F-actin and is circumscribed by a RhoA-based actomyosin contractile
      ring. During cytokinesis, constriction of the RhoA contractile ring is
      accompanied by Cdc42-mediated membrane outpocketing such that one spindle pole
      and one set of chromosomes are pulled into the Cdc42 enclosure. Unexpectedly, the
      guanine nucleotide exchange factor Ect2, which is necessary for contractile ring
      formation, does not colocalize with active RhoA. Polar body emission thus
      requires a classical RhoA contractile ring and Cdc42-mediated membrane
      protrusion.

PMID- 18804437
TI  - A subcortical maternal complex essential for preimplantation mouse embryogenesis.
AB  - We have identified a subcortical maternal complex (SCMC) that assembles during
      oocyte growth and is essential for zygotes to progress beyond the first embryonic
      cell divisions. At least four maternally encoded proteins contribute to this MDa
      complex: FLOPED, MATER, and TLE6 interact with each other while Filia binds
      independently to MATER. Although the transcripts encoding these proteins are
      degraded during meiotic maturation and ovulation, the SCMC proteins persist in
      the early embryo. The SCMC, located in the subcortex of eggs, is excluded from
      regions of cell-cell contact in the cleavage-stage embryo and segregates to the
      outer cells of the morulae and blastocyst. Floped(tm/tm) and/or Mater(tm/tm) eggs
      lack the SCMC but can be fertilized. However, these embryos do not progress
      beyond cleavage stage development and female mice are sterile. The proteins are
      conserved in humans, and similar maternal effect mutations may result in
      recurrent embryonic loss.

PMID- 18804438
TI  - Role of EVERGREEN in the development of the cymose petunia inflorescence.
AB  - Plants species diverge with regard to the time and place where they make flowers.
      Flowers can develop from apical meristems, lateral meristems, or both, resulting
      in three major inflorescence types known as racemes, cymes, and panicles,
      respectively. The mechanisms that determine a racemose architecture have been
      uncovered in Arabidopsis and Antirrhinum. To understand how cymes are specified,
      we studied mutations that alter the petunia inflorescence. Here we show that
      EVERGREEN (EVG) encodes a WOX homeodomain protein, which is exclusively expressed
      in incipient lateral inflorescence meristems (IMs), promoting their separation
      from the apical floral meristem (FM). This is essential for activation of DOUBLE
      TOP and specification of floral identity. Mutations that change the cymose
      petunia inflorescence into a solitary flower fully suppress the evg phenotype.
      Our data suggest a key role for EVG in the diversification of inflorescence
      architectures and reveal an unanticipated link between the proliferation and
      identity of meristems.

PMID- 18804439
TI  - Serum response factor is required for sprouting angiogenesis and vascular
      integrity.
AB  - Serum response factor (SRF) is a transcription factor that controls the
      expression of cytoskeletal proteins and immediate early genes in different cell
      types. Here, we found that SRF expression is restricted to endothelial cells
      (ECs) of small vessels such as capillaries in the mouse embryo. EC-specific Srf
      deletion led to aneurysms and hemorrhages from 11.5 days of mouse development
      (E11.5) and lethality at E14.5. Mutant embryos presented a reduced capillary
      density and defects in EC migration, with fewer numbers of filopodia in tip cells
      and ECs showing defects in actin polymerization and intercellular junctions. We
      show that SRF is essential for the expression of VE-cadherin and beta-actin in
      ECs both in vivo and in vitro. Moreover, knockdown of SRF in ECs impaired VEGF-
      and FGF-induced in vitro angiogenesis. Taken together, our results demonstrate
      that SRF plays an important role in sprouting angiogenesis and small vessel
      integrity in the mouse embryo.

PMID- 18804440
TI  - The frizzled extracellular domain is a ligand for Van Gogh/Stbm during
      nonautonomous planar cell polarity signaling.
AB  - The Frizzled (Fz) receptor is required cell autonomously in Wnt/beta-catenin and
      planar cell polarity (PCP) signaling. In addition to these requirements, Fz acts
      nonautonomously during PCP establishment: wild-type cells surrounding fz(-)
      patches reorient toward the fz(-) cells. The molecular mechanism(s) of
      nonautonomous Fz signaling are unknown. Our in vivo studies identify the
      extracellular domain (ECD) of Fz, in particular its CRD (cysteine rich domain),
      as critical for nonautonomous Fz-PCP activity. Importantly, we demonstrate
      biochemical and physical interactions between the FzECD and the transmembrane
      protein Van Gogh/Strabismus (Vang/Stbm). We show that this function precedes cell
      autonomous interactions and visible asymmetric PCP factor localization. Our data
      suggest that Vang/Stbm can act as a FzECD receptor, allowing cells to sense Fz
      activity/levels of their neighbors. Thus, direct Fz-Vang/Stbm interactions
      represent an intriguing mechanism that may account for the global orientation of
      cells within the plane of their epithelial field.

PMID- 18804441
TI  - Tissue deformation modulates twist expression to determine anterior midgut
      differentiation in Drosophila embryos.
AB  - Mechanical deformations associated with embryonic morphogenetic movements have
      been suggested to actively participate in the signaling cascades regulating
      developmental gene expression. Here we develop an appropriate experimental
      approach to ascertain the existence and the physiological relevance of this
      phenomenon. By combining the use of magnetic tweezers with in vivo laser
      ablation, we locally control physiologically relevant deformations in wild-type
      Drosophila embryonic tissues. We demonstrate that the deformations caused by germ
      band extension upregulate Twist expression in the stomodeal primordium. We find
      that stomodeal compression triggers Src42A-dependent nuclear translocation of
      Armadillo/beta-catenin, which is required for Twist mechanical induction in the
      stomodeum. Finally, stomodeal-specific RNAi-mediated silencing of Twist during
      compression impairs the differentiation of midgut cells, resulting in larval
      lethality. These experiments show that mechanically induced Twist upregulation in
      stomodeal cells is necessary for subsequent midgut differentiation.

PMID- 18804442
TI  - The cyclin-dependent kinase Cdk1 directly regulates vacuole inheritance.
AB  - In budding yeast, vacuole inheritance is tightly coordinated with the cell cycle.
      The movement of vacuoles and several other organelles is actin-based and is
      mediated by interaction between the yeast myosin V motor Myo2 and organelle
      specific adaptors. Myo2 binds to vacuoles via the adaptor protein Vac17, which
      binds to the vacuole membrane protein Vac8. Here we show that the yeast cyclin
      dependent kinase Cdk1 phosphorylates Vac17 and that phosphorylation of Vac17
      parallels cell cycle-dependent movement of the vacuole. Substitution of the Cdk1
      sites in Vac17 decreases its interaction with Myo2 and causes a partial defect in
      vacuole inheritance. This defect is enhanced in the presence of Myo2 with mutated
      phosphorylation sites. Thus, Cdk1 appears to control the timing of vacuole
      movement. The presence of multiple predicted Cdk1 sites in other organelle
      specific myosin V adaptors suggests that the inheritance of other cytoplasmic
      organelles may be regulated by a similar mechanism.

PMID- 18804443
TI  - Biological characterization of Trypanosoma cruzi stocks from domestic and
      sylvatic vectors in Sierra Nevada of Santa Marta, Colombia.
AB  - Sierra Nevada of Santa Marta is one of the most endemic regions of Chagas disease
      in Colombia. In this study, we compared the biological behavior and genetic
      features of Trypanosoma cruzi stocks that were isolated from domestic and
      sylvatic insects in this area. Rhodnius prolixus (from domestic environments) and
      Triatoma dimidiata (from sylvatic, peridomestic and domestic environments) are
      the most important vectors in this region. Genetic characterization showed that
      all stocks corresponded to T. cruzi I, but LSSP-PCR analyses indicated that some
      genotypes were present in both environments. Biological characterization in vitro
      showed a low growth rate in sylvatic T. cruzi stocks and in some domestic T.
      cruzi stocks, possibly indicating the presence of stocks with similar behavior in
      both transmission cycles. In parallel, in vivo behavioral analysis also indicated
      that T. cruzi stocks are variable and this species did not show a correlation
      between the environments where they were isolated. In addition, all stocks
      demonstrated a low mortality rate and histopathological lesions in heart,
      skeletal muscle and colon tissue. Moreover, our data indicated that
      experimentally infected chagasic mice displayed a relation between their
      myocardial inflammation intensity, parasitism tissue and parasite load using the
      qPCR. In conclusion, our results indicate that the T. cruzi stocks present in
      SNSM have similar biological behavior and do not show a correlation with the
      different transmission cycles. This could be explained by the complex
      transmission dynamics of T. cruzi in Sierra Nevada of Santa Marta, where hosts,
      vectors (e.g., T. dimidiata) and reservoirs circulate in both environments due to
      the close contact between the two transmission cycles, favoring environment
      overlapping. This knowledge is an important key to understanding the epidemiology
      and pathology of Chagas disease in this Colombian region. Furthermore, our
      findings could be of significant use in the design of control strategies
      restricted to a specified endemic region.

PMID- 18804444
TI  - Localization of 13 one-helix integral membrane proteins in photosystem II
      subcomplexes.
AB  - Photosystem II is a multimeric protein complex of the thylakoid membrane in
      chloroplasts. Approximately half of the at least 26 different integral membrane
      protein subunits have molecular masses lower than 10 kDa. After one-dimensional
      (1D) or two-dimensional (2D) polyacrylamide gel electrophoresis (PAGE)
      separation, followed by enzymatic digestion of detected proteins, hardly any of
      these low-molecular-weight (LMW) subunits are detectable. Therefore, we developed
      a method for the analysis of highly hydrophobic LMW proteins. Intact proteins are
      extracted from acrylamide gels using a mixture of formic acid and organic
      solvent, precipitated with acetone, and analyzed by "top-down" mass spectrometry
      (MS). After offline nanoESI (electrospray ionization) MS, all LMW one-helix
      proteins from photosystem II were detected. In the four detected photosystem II
      supercomplexes of Nicotiana tabacum wild-type plants, 11 different one-helix
      proteins were identified as PsbE, -F, -H, -I, -K, -L, -M, -Tc, -W, and two
      isoforms of PsbX. The proteins PsbJ, -Y1, and -Y2 were localized in the buffer
      front after blue native (BN) PAGE, indicating their release during
      solubilization. Assembled PsbW is detected exclusively in supercomplexes, whereas
      it is absent in photosystem II core complexes, corroborating the protein's
      function for assembly of the light-harvesting complexes. This approach will
      substantiate gel-blot immunoanalysis for localization and identification of LMW
      protein subunits in any membrane protein complex.

PMID- 18804445
TI  - High fractions of exogenous DNA in human buccal samples reduce the quality of
      large-scale genotyping.
AB  - Buccal cell samples are considered a reliable source of DNA for genotyping
      studies. However, a potential drawback is the presence of exogenous DNA that is
      coextracted with human genomic DNA. A set of saliva and cheek swab samples, in
      which the fraction of human DNA varies from 10 to 96%, was genotyped using the
      Affymetrix Mapping 500 K Array. Samples containing less than 30% human DNA
      performed poorly in terms of accuracy and reliability. Therefore, we recommend
      quantitating the amount of human DNA in buccal samples to be used for large-scale
      genotyping and eliminating samples with less than 30% human DNA.

PMID- 18804446
TI  - Spectroscopic and kinetic studies of Nor1, a cytochrome P450 nitric oxide
      reductase from the fungal pathogen Histoplasma capsulatum.
AB  - The fungal respiratory pathogen Histoplasma capsulatum evades the innate immune
      response and colonizes macrophages during infection. Although macrophage
      production of the antimicrobial effector nitric oxide (NO) restricts H.
      capsulatum growth, the pathogen is able to establish a persistent infection. H.
      capsulatum contains a P450 nitric oxide reductase homologue (NOR1) that may be
      important for detoxifying NO during infection. To characterize the activity of
      this putative P450 enzyme, a 404 amino acid fragment of Nor1p was expressed in
      Escherichia coli and purified to homogeneity. Spectral characterization of Nor1p
      indicated that it was similar to other fungal P450 nitric oxide reductases. Nor1p
      catalyzed the reduction of NO to N2O using NADH as the direct reductant. The K(M)
      for NO was determined to be 20 microM and the k(cat) to be 5000 min(-1).
      Together, these results provide evidence for a protective role of a P450 nitric
      oxide reductase against macrophage-derived NO.

PMID- 18804447
TI  - Identification and characterization of the ER/lipid droplet-targeting sequence in
      17beta-hydroxysteroid dehydrogenase type 11.
AB  - 17beta-Hydroxysteroid dehydrogenase type 11 (17betaHSD11) is mostly localized on
      the endoplasmic reticulum (ER) membrane under normal conditions and redistributes
      to lipid droplets (LDs) when the formation of LDs is induced. In this study,
      confocal microscopy analyses of the subcellular localization of the mutated
      17betaHSD11 proteins in cells with or without LDs revealed that both an N
      terminal hydrophobic sequence and an adjacent sequence that has a weak homology
      with the PAT motif are independently necessary and both parts together (28 amino
      acid residues in total) are sufficient for the dual localization of 17betaHSD11.
      Mutation analyses suggest that the PAT-like motif in 17betaHSD11 will not be
      functionally similar to the canonical PAT motif. Hsp60 was identified as a
      possibly interacting protein with the PAT-like motif, and biochemical and
      microscopic analyses suggest that Hsp60 may be partly, but not necessarily
      involved in recognition of the PAT-like part of the targeting sequence of
      17betaHSD11.

PMID- 18804448
TI  - Lack of cholesterol mobilization in islets of hormone-sensitive lipase deficient
      mice impairs insulin secretion.
AB  - The observations that hormone-sensitive lipase (HSL) is located in close
      association to insulin granules in beta-cells and that cholesterol ester
      hydrolase activity is completely blunted in islets of HSL null mice made us
      hypothesize that the role of HSL in beta-cells is to provide cholesterol for the
      exocytosis of insulin. To test this hypothesis, wild type (wt) and HSL null
      islets were depleted of plasma membrane cholesterol using methyl-beta
      cyclodextrin (mbetacd). A significant reduction in insulin secretion from HSL
      null islets was observed whereas wt islets were unaffected. Using synaptosomal
      protein of 25 kDa (SNAP-25) as indicator of cholesterol-rich microdomains,
      confocal microscopy was used to show that HSL null beta-cells treated with
      mbetacd contained fewer clusters than wt beta-cells. These results indicate that
      HSL plays an important role in insulin secretion by providing free cholesterol
      for the formation and maintenance of cholesterol-rich patches for docking of
      SNARE-proteins to the plasma membrane.

PMID- 18804449
TI  - Ethanol intoxication increases hepatic N-lysyl protein acetylation.
AB  - The acetylation of the epsilon-amino group of lysine to form N-acetyl lysine (N
      AcLys)-modified proteins regulates the activity of metabolic proteins. Because of
      the multiple effects of ethanol upon hepatic metabolism, it was hypothesized that
      ethanol exposure increases the hepatic content of N-AcLys-modified proteins. To
      test this hypothesis, rats or mice were exposed to ethanol using a liquid diet
      regimen. Content of N-AcLys-modified proteins was elevated more than 5-fold after
      6 weeks of ethanol exposure and persisted after ethanol withdrawal. Use of CYP2E1
      knockout mice demonstrated that ethanol-induced acetylation was not dependent
      solely on CYP2E1 expression. The mitochondrial content of N-AcLys-modified
      proteins was elevated almost 5-fold following 6 weeks of ethanol exposure.
      Mitochondrial content of the deacetylase Sirt3 was unchanged by 6 weeks of
      ethanol exposure. These data indicate ethanol intoxication changes the
      acetylation status of, and likely the activity of, multiple mitochondrial
      proteins.

PMID- 18804450
TI  - Derivation of cranial neural crest-like cells from human embryonic stem cells.
AB  - The neural crest is a transient population of multipotent progenitors
      contributing to a diverse array of tissues throughout the vertebrate embryo.
      Embryonic stem (ES) cells are able to form embryoid body and spontaneously
      differentiate to various lineages, following a reproducible temporal pattern of
      development that recapitulates early embryogenesis. Embryoid bodies were
      triturated and the dissociated cells were processed for fluorescence-activated
      cell sorting (FACS), and more than 1% of cells were identified as frizzled
      3(+)/cadherin-11(+). Expression of marker genes associated with various terminal
      fates was detected for chondrocytes, glia, neurons, osteoblasts and smooth
      muscles, indicating that the FACS-sorted frizzled-3(+)/cadherin-11(+) cells were
      multipotent progenitor cells capable of differentiating to fates associated with
      cranial neural crest. Moreover, the sorted cells were able to self-renew and
      maintain multipotent differentiation potential. The derivation of cranial neural
      crest-like multipotent progenitor cells from ES cells provides a new tool for
      cell lineage analysis of neural crest in vitro.

PMID- 18804451
TI  - The capsaicin receptor participates in artificial sweetener aversion.
AB  - Artificial sweeteners such as saccharin, aspartame, acesulfame-K, and cyclamate
      produce at high concentrations an unpleasant after-taste that is generally
      attributed to bitter and metallic taste sensations. To identify receptors
      involved with the complex perception of the above compounds, preference tests
      were performed in wild-type mice and mice lacking the TRPV1 channel or the T1R3
      receptor, the latter being necessary for the perception of sweet taste. The
      sweeteners, including cyclamate, displayed a biphasic response profile, with the
      T1R3 mediated component implicated in preference. At high concentrations
      imparting off-taste, omission of TRPV1 reduced aversion. In a heterologous
      expression system the Y511A point mutation in the vanilloid pocket of TRPV1 did
      not affect saccharin and aspartame responses but abolished cyclamate and
      acesulfame-K activities. The results rationalize artificial sweetener tastes and
      off-tastes by showing that at low concentrations, these molecules stimulate the
      gustatory system through the hedonically positive T1R3 pathway, and at higher
      concentrations, their aversion is partly mediated by TRPV1.

PMID- 18804452
TI  - Functional adaptation to oxidative stress by memory T cells: an analysis of the
      role in the cardiovascular disease process.
AB  - T cells participate in combating infection and critically determine the outcomes
      in any given disease process. Impaired immune response occurs in a number disease
      processes such as in cancer and atherosclerosis although the underlying
      mechanisms are still not fully understood. This article gives an up-to-date
      review of T cells development and functional adaptation to pathophysiological
      stimuli and participation in the cardiovascular disease process. In addition, we
      have discussed the signaling pathways controlled by the microenvironment that
      determine T cells function and resultant type of immune response. We have also
      discussed in detail how oxidative stress is a key component of the micro
      environmental interaction.

PMID- 18804453
TI  - A new Kaliotoxin selective towards Kv1.3 and Kv1.2 but not Kv1.1 channels
      expressed in oocytes.
AB  - In this paper were described the purification, the sequencing, and the
      immunological and biological characterization of a new Kaliotoxin analog, Aam
      KTX, from the venom of the scorpion Androctonus amoreuxi. The toxin effects on
      three cloned Kv channels (Kv1.1, Kv1.2, and Kv1.3) were investigated in Xenopus
      oocytes using electrophysiology experiments. The Aam-KTX preference for Kv1.3
      channel versus Kv1.2 was expected (EC(50) values, 1.1+/-0.02 and 10.4+/-1.5 nM,
      respectively) but its total inefficacy on Kv1.1 was very surprising. 3D molecular
      modeling of Aam-KTX brought putative answers to this difference in selectivity.

PMID- 18804454
TI  - Organic osmolyte channels in malaria-infected erythrocytes.
AB  - Infection of human erythrocytes with the malaria parasite Plasmodium falciparum
      induces activation of organic osmolyte and anion channels in the host cell
      membrane. These channels supply the intraerythrocytic parasite with nutrients,
      dispose of metabolic waste products, adjust the host electrolyte concentrations
      to the parasite's needs, and lower the colloid osmotic pressure, thus preventing
      premature hemolysis of the osmotically challenged host cell. Four different types
      of anion channels (CFTR, ClC-2 or PSAC, an 18pS inward rectifier, and an 80pS
      outward rectifier) have been identified in human erythrocytes. Here, we show that
      the 80pS channels underlie a serum albumin-dependent anion current. Both, the
      parasite in vitro development and the organic osmolyte permeability of the
      parasitized erythrocyte, reportedly depend on serum albumin, highlighting the
      pivotal functional significance of the 80pS channel for the intraerythrocytic
      parasite development.

PMID- 18804455
TI  - Sustained depolarization-induced propagation of [Ca2+]i oscillations in cultured
      DRG neurons: the involvement of extracellular ATP and P2Y receptor activation.
AB  - Recently emerging evidence implicates a number of neuroactive substances and
      their receptors in mediating complex cell-to-cell communications in the ganglia.
      In the present study, we characterized the nonsynaptic chemical coupling mediated
      by extracellular ATP in dorsal root ganglia (DRG) neuron cultures by using the
      real time imaging of ATP, whole-cell patch clamping, in conjunction with confocal
      calcium imaging. Sustained depolarization by electrical stimulation evoked
      intracellular Ca2+ concentrations ([Ca2+]i) oscillations in individual DRG
      neurons, and subsequent ATP-dependent propagation [Ca2+]i oscillations to
      surrounding non-stimulated neighbors. [Ca2+]i oscillations were suppressed by
      inositol-1,4,5-trisphosphate (IP3) receptor antagonist 2-APB, but not ryanodine.
      The propagation of [Ca2+]i oscillations was prevented by the presence of the ATP
      degrading enzyme, apyrase, and completely abolished by the blockase of G protein
      coupled purinergic receptors-PLC-IP3 pathway with suramin, U73122 or 2-APB. In
      parallel, sustained depolarization elicited robust ATP release and diffusion from
      the stimulation site. Moreover, exogenous application of ATP to DRG cultures in
      large concentration elicits the [Ca2+]i oscillations in most neurons. Taken
      together, this data demonstrates that sustained membrane depolarization elicited
      ATP release, acting through a highly sensitive P2Y receptors/IP3-mediated
      signaling pathway to mediate the propagation of intercellular Ca2+ signaling,
      which suggest a novel signaling pathway for neuronal communication in DRG.

PMID- 18804456
TI  - Myelin-forming ability of Schwann cell-like cells induced from rat adipose
      derived stem cells in vitro.
AB  - Although Schwann cell (SC) transplantation can enhance peripheral and central
      nerve repair experimentally, it is difficult to generate sufficient SC quickly
      for clinical application. So alternative cell systems for SC are desired. SC-like
      cells induced from adipose-derived stem cells (ADSC) may be one of the ideal
      alternative cell systems for SC. However, myelin-forming ability, which is the
      most important characteristics and function of SC, has not been investigated in
      SC-like cells from ADSC up to now. In this experiment, ADSC were harvested from
      rat inguinal fat pad. Rat ADSC were fibroblast-like in shape, almost all the
      cells expressed mesodermal marker fibronectin, and only few cells expressed
      neural stem cell marker nestin. A mixture of glial growth factors (Heregulin,
      bFGF, PDGF and forskolin) could induce rat ADSC into SC-like cells. SC-like cells
      were spindle-like in shape and expressed glial markers GFAP and S100, similar to
      genuine SC. When intracellular cAMP was increased, SC-like cells could express
      myelin protein p0. More importantly, when co-cultured with rat pheochromocytoma
      cell line (PC12 cells), SC-like cells could induce the differentiation of PC12
      cells rapidly and form myelin structures with PC12 cells in vitro. Our data
      further demonstrated that SC-like cells from ADSC were able to form myelins and
      these cells may benefit the treatment of peripheral and central nerve injuries.

PMID- 18804457
TI  - Neural correlates of immediate and delayed word recognition memory: an MEG study.
AB  - We investigated the neural correlates of immediate and delayed word recognition
      memory using whole head magnetoencephalography (MEG). Event-related potential
      (ERP) and event-related field (ERF) were simultaneously recorded from 10 subjects
      while performing a continuous recognition memory task. Subjects were required to
      determine whether the word was "new" (never before presented) or "old" (presented
      previously). Old items were presented either immediately or delayed with five
      intervening words, and the words presented only once were referred to as new
      words. The grand average ERP waveform showed that immediate repetition was
      associated with early P300 and absence of N400, while delayed repetition and new
      word were associated with late P300 and presence of N400. Three ERF components
      were observed for immediate repetition, while four components were observed for
      delayed repetition and new word conditions. M1 and M2 were observed across all
      stimulus-presentation conditions. M3 with medial temporal generators was observed
      only in delayed repetition and new word conditions. M4 was observed earlier in
      the immediate repetition than in the delayed repetition and new-word conditions.
      For M4 generators, cingulate gyrus activations were observed for all stimulus
      presentation conditions. In addition, activations in the medial temporal areas
      were observed for both repetition conditions. These results suggest that
      immediate and delayed recognition memory have similar neural networks except for
      the additional involvement of medial temporal areas in delayed recognition
      memory. The functional roles of M3 and M4 peaks were discussed in terms of
      functional significance of N400 and early/late P300 ERP peaks, which correspond
      to M3 and M4, respectively.

PMID- 18804459
TI  - Higher frequency of abnormal serum angiopoietin-like protein 3 than abnormal
      cholesteryl ester transfer protein in Japanese hyperalphalipoproteinemic
      subjects.
AB  - BACKGROUND: Either a decrease of cholesteryl ester transfer protein (CETP) or an
      increase of angiopoietin-like protein 3 (ANGPTL3) in plasma has been shown to
      increase HDL-cholesterol (HDL-C) levels. However, as yet, it is not known which
      protein is more strongly associated with the modulation of HDL in the Japanese
      hyperalphalipoproteinemic (HALT) subjects. METHODS: The serum concentration of
      ANGPTL3 and CETP, together with total cholesterol (TC), triglycerides (TG),
      adiponectin and ApoE phenotypes were determined in three groups with different
      HDL-C concentrations: low, <40 mg/dl (n=51); normal, 40-90 mg/dl (n=126) and
      high, >90 mg/dl (n=89) in the average Japanese population. RESULTS: The normal
      range (mean+/-2SD) of serum ANGPTL3 (218+/-144 ng/ml) and CETP (1.29+/-0.90
      microg/ml) were determined in cases with 40-90 mg/dl HDL-C concentration. The
      frequency of abnormally high ANGPTL3 cases (>362 ng/ml) were found to be
      significantly greater (44%) compared with those of low CETP cases (<0.39
      microg/ml, 4.5%) in HALT cases (>90 mg/dl). ANGPTL3 showed a high correlation
      with HDL-C (r=0.67, P<0.0001) and adiponectin (r=0.57, P<0.0001), but not with
      CETP. CONCLUSION: In average Japanese population, abnormally higher frequency of
      increased ANGPTL3 prevail in HALT cases as compared with cases with low CETP.
      These findings suggest that ANGPTL3, the inhibitor of endothelial lipase, may be
      more strongly associated with increased HDL-C rather than CETP in plasma.
      Accordingly, ANGPTL3 seems to be a better target for the modulation of HDL-C.

PMID- 18804458
TI  - TGF beta2-induced changes in LRP-1/T beta R-V and the impact on lysosomal A beta
      uptake and neurotoxicity.
AB  - Numerous studies suggest a central role for the low-density lipoprotein receptor
      related protein/transforming growth factor beta receptor V in Alzheimer's
      Disease. We continue our investigation of a ligand for this receptor,
      transforming growth factor beta2, which is also implicated in Alzheimer Disease
      pathogenesis, but whose mechanism(s) remain elusive. Confocal imaging reveals
      that transforming growth factor beta2 rapidly targets amyloid beta peptide to the
      lysosomal compartment in cortical neurons and induces cell death. Low-density
      lipoprotein receptor-related protein/transforming growth factor beta receptor V
      is known as an endocytic receptor, delivering proteins to the lysosomal
      compartment for degradation. Transforming growth factor beta2 may alter this
      pathway resulting in increased uptake, intracellular accumulation and toxicity of
      amyloid beta peptide. RT-PCR and Western blot analysis of transforming growth
      factor beta2-treated cells demonstrate that transforming growth factor beta2
      modestly increases the mRNA and protein levels of low-density lipoprotein
      receptor-related protein/transforming growth factor beta receptor V as well as
      increases the uptake activity. Furthermore, transforming growth factor beta2
      alters the morphology and numbers of lysosomes in neurons. Lucifer Yellow and
      lysosomal hydrolase analysis show that transforming growth factor beta2 makes
      lysosomal membranes unstable and leaky and this effect is exacerbated with the
      addition of amyloid beta protein. Our data support a key role for low-density
      lipoprotein receptor-related protein/transforming growth factor beta receptor V
      in mediating transforming growth factor beta2 enhancement of amyloid beta peptide
      uptake and neurotoxicity.

PMID- 18804460
TI  - Wnt6 signaling regulates heart muscle development during organogenesis.
AB  - Mesodermal tissue with heart forming potential (cardiogenic mesoderm) is induced
      during gastrulation. This cardiogenic mesoderm later differentiates into heart
      muscle tissue (myocardium) and non-muscular heart tissue. Inhibition of Wnt/beta
      catenin signaling is known to be required early for induction of cardiogenic
      mesoderm; however, the identity of the inhibiting Wnt signal itself is still
      elusive. We have identified Wnt6 in Xenopus as an endogenous Wnt signal, which is
      expressed in tissues close to and later inside the developing heart. Our loss-of
      function experiments show that Wnt6 function is required in the embryo to prevent
      development of an abnormally large heart muscle. We find, however, that Wnt6 is
      not required as expected during gastrulation stages, but later during
      organogenesis stages just before cells of the cardiogenic mesoderm begin to
      differentiate into heart muscle (myocardium). Our gain-of-function experiments
      show that Wnt6 and also activated canonical Wnt/beta-catenin signaling are
      capable of restricting heart muscle development at these relatively late stages
      of development. This repressive role of Wnt signaling is mediated initially via
      repression of cardiogenic transcription factors, since reinstatement of GATA
      function can rescue expression of other cardiogenic transcription factors and
      downstream cardiomyogenic differentiation genes.

PMID- 18804461
TI  - Chronic left atrial volume overload abbreviates the action potential duration of
      the canine pulmonary vein myocardium via activation of IK channel.
AB  - Electrophysiological properties of the pulmonary vein myocardium were assessed in
      a canine chronic atrioventricular block model resulting in left atrial volume
      overload. Five chronic atrioventricular block dogs and five sham-operated dogs
      were used. The heart was removed two months after a surgical procedure causing
      atrioventricular block, when atrial structural remodeling was established.
      Standard microelectrode penetrations were made with glass microelectrodes to
      obtain action potential signals of left atrium and pulmonary vein myocardia. The
      resting membrane potential in the pulmonary vein was more positive than that in
      the left atrium (-69 mV vs -74 mV) in both animal groups. The action potential
      duration at 50% repolarization of the pulmonary vein was shorter in the chronic
      atrioventricular block dogs than in the sham-operated dogs (38 ms vs 63 ms),
      whereas no significant difference was detected in the action potential duration
      of the left atrium between the two animal groups (67 ms vs 61 ms). The action
      potential duration of the pulmonary vein in the chronic atrioventricular block
      dogs was prolonged by charybdotoxin but not by iberiotoxin. Such prolongation was
      not observed in the normal pulmonary vein. These results suggest that long-term
      left atrial dilatation shortened the action potential duration of pulmonary vein
      myocardium, which may be associated with activation of the intermediate
      conductance Ca2+-activated K+ channel (IK channel).

PMID- 18804462
TI  - Nedd4, a human ubiquitin ligase, affects actin cytoskeleton in yeast cells.
AB  - Human Nedd4 ubiquitin ligase is involved in protein trafficking, signal
      transduction and oncogenesis. Nedd4 with an inactive WW4 domain is toxic to yeast
      cells. We report here that actin cytoskeleton is abnormal in yeast cells
      expressing the NEDD4 or NEDD4w4 gene and these cells are more sensitive to
      Latrunculin A, an actin-depolymerizing drug. These phenotypes are less pronounced
      when a mutation inactivating the catalytic domain of the ligase has been
      introduced. In contrast, overexpression of the LAS17 gene, encoding an activator
      of the Arp2/3 actin nucleating complex, is detrimental to NEDD4w4-expressing
      cells. The level of Las17p is increased in cells overproducing Nedd4w4 and this
      depends partially on its catalytic domain. Expression of genes encoding Nedd4
      variants, like overexpression of LAS17, suppresses the growth defect of the arp2
      1 strain. Our results suggest that human Nedd4 ligase inhibits yeast cell growth
      by disturbing the actin cytoskeleton, in part by increasing Las17p level, and
      that Nedd4 ubiquitination targets may include actin cytoskeleton-associated
      proteins conserved in evolution.

PMID- 18804463
TI  - Effects of vagus nerve stimulation on rat hippocampal progenitor proliferation.
AB  - Vagus nerve stimulation (VNS), used in the treatment of epilepsy, was approved
      recently for treatment-resistant depression. The mechanisms of action of the VNS
      anti-depressive effects are not yet fully elucidated. Modulation of hippocampal
      neurogenesis has been proposed as an important factor in depression pathogenesis.
      We evaluated the effects of VNS on hippocampal progenitor turnover in the adult
      rat brain. Rats receiving VNS at the output current of 0.75 mA VNS for 2 days
      showed a significant 50% increase in dentate gyrus BrdU-incorporation consistent
      with an increase in progenitor proliferation. Output currents of 0.5 or 1.5 mA
      yielded non-significant trends for increased BrdU-labeling indicating an inverted
      U-shaped proliferative dose response to VNS as previously reported for other VNS
      induced effects. Specific analysis for progenitor survival revealed no effects by
      VNS on dentate gyrus BrdU-labeling. These results suggest that VNS induced an
      increase in the number of available progenitor cells in the adult rat dentate
      gyrus by a mechanism presumably involving increased progenitor proliferation.

PMID- 18804464
TI  - Collagen-binding motif peptide, a cleavage product of osteopontin, stimulates
      human neutrophil chemotaxis via pertussis toxin-sensitive G protein-mediated
      signaling.
AB  - The collagen-binding motif (CBM) peptide, a cleavage product of osteopontin
      (OPN), stimulated intracellular calcium increase in human neutrophils. CBM
      peptide-stimulated calcium was inhibited by pertussis toxin (PTX), suggesting the
      influence of PTX-sensitive G-proteins. In addition CBM peptide stimulated the
      chemotactic migration of human neutrophils and human monocytes. CBM peptide
      induced neutrophil chemotaxis was completely inhibited by PTX, once again
      indicating the influence of Gi proteins. CBM peptide was also found to induce
      mitogen activated protein kinase activation. CBM peptide-induced neutrophil
      chemotaxis was mediated by p38 kinase as well as an extracellular signal
      regulated protein kinase. Taken together, the results suggest that a cleavage
      product of OPN, CBM peptide, initiates immune responses by inducing neutrophil
      trafficking via certain PTX-sensitive cell surface receptors.

PMID- 18804465
TI  - Functional implications of the proximal site hydrogen bonding network in
      Vitreoscilla hemoglobin (VHb): role of Tyr95 (G5) and Tyr126 (H12).
AB  - Although Vitreoscilla hemoglobin (VHb) carries a conventional globin fold, its
      proximal site geometry is unique in having a hydrogen-bonding network between
      proximal site residues, HisF8-TyrG5-GluH23 and TyrG5-TyrH12. TyrG5 and TyrH12
      were mutated to study their relevance in VHb function. VHb G5 mutants (Tyr95Phe
      and Tyr95Leu showed no stable oxyform and nitric oxide dioxygenase activity,
      whereas, VHb H12 mutants (Tyr126Phe and Tyr126Leu) displayed little change in
      their oxygen affinity indicating a crucial role of Tyr95 in protein function. The
      VHb H12 mutant, Tyr126Leu, enhanced the intracellular pool of oxygen and cell
      growth better than VHb. Molecular modeling suggests that the replacement of
      tyrosine with leucine in Tyr126Leu creates an opening on the protein surface that
      may facilitate oxygen diffusion and accumulation.

PMID- 18804466
TI  - Nuclear matrix contains novel WD-repeat and disordered-region-rich proteins.
AB  - To find novel proteins predicted to participate in the formation of nuclear
      bodies, nuclear speckles, and nuclear macro-protein complexes, we applied
      proteome analysis to a HeLa cell nuclear matrix fraction. Proteins in the
      fraction were separated by SDS-PAGE, digested with trypsin, and analyzed by
      nanoflow liquid chromatography-iontrap-tandem mass spectrometry. Three hundred
      and thirty three proteins including 39 novel ones were identified. Seven WD
      repeat proteins and 16 disordered region-rich proteins, which act frequently as
      scaffolding proteins for macro-protein complexes, were found amongst the novel
      proteins.

PMID- 18804467
TI  - Interaction of grape ASR proteins with a DREB transcription factor in the
      nucleus.
AB  - ASR proteins (abscissic acid, stress, ripening induced) are involved in plant
      responses to developmental and environmental signals but their biological
      functions remain to be elucidated. Grape ASR gene (VvMSA) encodes a new
      transcription factor regulating the expression of a glucose transporter. Here, we
      provide evidence for some polymorphism of grape ASRs and their identification as
      chromosomal non-histone proteins. By the yeast two-hybrid approach, a protein
      partner of VvMSA is isolated and characterized as an APETALA2 domain
      transcription factor. Interaction of the two proteins is further demonstrated by
      the BiFC approach and the exclusive nuclear localization of the heterodimer is
      visualized.

PMID- 18804468
TI  - Brief cross-linking of Fas/APO-1 (CD95) triggers engulfment of pre-apoptotic
      target cells.
AB  - Macrophage clearance of dying cells is of crucial importance to maintain tissue
      homeostasis. Here, we show that brief treatment (15min) of Jurkat T cells with
      agonistic anti-Fas antibodies or recombinant Fas ligand results in efficient
      phagocytosis by human monocyte-derived macrophages prior to the occurrence of
      common biomarkers of apoptosis. Similar findings were obtained when using primary
      human T cells. Macrophage engulfment of pre-apoptotic target cells was suppressed
      in the absence of serum. Moreover, pre-apoptotic cells secreted annexin I and
      administration of Boc1, a formyl peptide receptor/lipoxin receptor antagonist
      markedly attenuated their engulfment. Finally, pre-apoptotic Jurkat cells induced
      lower macrophage production of tumor necrosis factor-alpha and higher production
      of interleukin-10 in comparison to apoptotic target cells.

PMID- 18804469
TI  - Dexamethasone increases angiopoietin-1 and quiescent hematopoietic stem cells: a
      novel mechanism of dexamethasone-induced hematoprotection.
AB  - Angiopoietin-1 (Ang-1) is known to have hematoprotective effects by increasing
      the quiescence of hematopoietic stem cells. However, it remains to be determined
      if the upregulation of Ang-1 and the subsequent increase in the quiescence of
      hematopoietic stem cells are also involved in the dexamethasone (Dex)-mediated
      bone marrow protection. Here Western blotting and flow cytometric analyses
      demonstrate that Dex increases the levels of Ang-1 in mouse bone marrow and the
      quiescence of hematopoietic stem cells. Our data for the first time suggest that
      the increased quiescence of hematopoietic stem cells provides a novel mechanism
      of Dex-induced hematoprotection.

PMID- 18804470
TI  - TPA primes alpha2beta1 integrins for cell adhesion.
AB  - Integrin avidity is regulated by changes in the conformation of the heterodimer
      and cluster formation. We measured cell adhesion by integrin alpha2beta1 (CHO
      alpha2) to collagen at short contact times (0.5-60s) by single cell force
      spectroscopy (SCFS). The adhesion increased rapidly with contact time and was
      further strengthened by the addition of 12-O-tetradecanoylphorbol-13-acetate
      (TPA), a protein kinase C (PKC) and integrin activator. TPA also improved the
      strength of adhesive units. Furthermore, changes in membrane nanotube properties
      indicated better coupling of integrins to the cell cytoskeleton. We conclude that
      in addition to increasing integrin avidity TPA strengthens integrin-cytoskeletal
      linkage.

PMID- 18804471
TI  - Respiratory mutations lead to different pleiotropic effects on OXPHOS complexes
      in yeast and in human cells.
AB  - Pleiotropic effects in the oxidative phosphorylation pathway (OXPHOS) were
      investigated in yeast respiratory mutants and in cells from patients with OXPHOS
      genetic alterations. The main differences between yeast and human cells were (1)
      the site of the primary defect that was associated with pleiotropic effects,
      yeast complex V and human complex IV, and (2) the nature of the complex targeted
      by the secondary effect, yeast complex IV and human complex I. The pleiotropic
      effects did not correlate with the organization of OXPHOS into supercomplexes and
      their functional consequences appeared to be a slowing down of the respiratory
      chain in order to avoid either an increase in the membrane potential or the
      accumulation of reduced intermediary components of the respiratory chain.

PMID- 18804472
TI  - Regulated catalysis of extracellular nucleotides by vascular CD39/ENTPD1 is
      required for liver regeneration.
AB  - BACKGROUND & AIMS: Little is known about how endothelial cells respond to injury,
      regulate hepatocyte turnover and reconstitute the hepatic vasculature. We aimed
      to determine the effects of the vascular ectonucleotidase CD39 on sinusoidal
      endothelial cell responses following partial hepatectomy and to dissect
      purinergic and growth factor interactions in this model. METHODS: Parameters of
      liver injury and regeneration, as well as the kinetics of hepatocellular and
      sinusoidal endothelial cell proliferation, were assessed following partial
      hepatectomy in mice that do not express CD39, that do not express ATP/UTP
      receptor P2Y2, and in controls. The effects of extracellular ATP on vascular
      endothelial growth factor (VEGF), hepatocyte growth factor (HGF), and interleukin
      6 responses were determined in vivo and in vitro. Phosphorylation of the
      endothelial VEGF receptor in response to extracellular nucleotides and growth
      factors was assessed in vitro. RESULTS: After partial hepatectomy, expression of
      the vascular ectonucleotidase CD39 increased on sinusoidal endothelial cells.
      Targeted disruption of CD39 impaired hepatocellular regeneration, reduced
      angiogenesis, and increased hepatic injury, resulting in pronounced vascular
      endothelial apoptosis, and decreased survival. Decreased HGF release by
      sinusoidal endothelial cells, despite high levels of VEGF, reduced paracrine
      stimulation of hepatocytes. Failure of VEGF receptor-2/KDR transactivation by
      extracellular nucleotides on CD39-null endothelial cells was associated with P2Y2
      receptor desensitization. CONCLUSIONS: Regulated phosphohydrolysis of
      extracellular nucleotides by CD39 coordinates both hepatocyte and endothelial
      cell proliferation following partial hepatectomy. Lack of CD39 activity is
      associated with decreased hepatic regeneration and failure of vascular
      reconstitution.

PMID- 18804473
TI  - Effects of maternal exposure to ammonium perchlorate on thyroid function and the
      expression of thyroid-responsive genes in Japanese quail embryos.
AB  - Perchlorate, a known thyroid disruptor, is deposited in eggs of exposed female
      birds, raising concerns that the embryos from these eggs may become hypothyroid,
      which may in turn affect the development and function of thyroid-dependent
      organs. We hypothesized that exposure to ammonium perchlorate (AP) would decrease
      hen and embryonic thyroid function and affect the expression of thyroid
      responsive genes in embryonic brain and liver. Laying Japanese quail hens were
      treated with 2000 mg/l or 4000 mg/l AP in drinking water. Thyroid status and
      expression of thyroid-responsive genes were examined in the embryos from eggs of
      exposed hens. Perchlorate exposure led to hypothyroidism in hens from both
      treatment groups; egg production was decreased in the high dosage group only.
      Embryos from eggs of perchlorate-exposed hens had hypertrophied thyroid glands
      and significantly lower thyroidal hormone storage, indicating hypothyroidism in
      these embryos. The embryonic hypothyroidism was associated with decreased
      embryonic growth, delayed hatching and greater mortality during hatching. The
      mRNA level of type 2 deiodinase (D2) in the liver of embryos from eggs of
      perchlorate-exposed hens was increased compared to the control embryos, a
      compensatory response that increases the production of metabolically active T(3).
      However, the mRNA levels of D2 and RC3 in the brain were not affected. These
      results suggest that the embryonic brain is protected from hypothyroidism by
      other mechanisms known to influence hormone entry into and exit from the brain.
      Our study shows that maternal perchlorate exposure led to embryonic
      hypothyroidism and may have interfered with embryonic development.

PMID- 18804474
TI  - Acoustic characteristics, early experience, and endocrine status interact to
      modulate female zebra finches' behavioral responses to songs.
AB  - Female songbirds use male songs as an important criterion for mate selection.
      Properties of male songs are thought to indicate the male's quality as a
      potential mate. Song preferences in female zebra finches are known to be
      influenced by two factors--early auditory experience and the acoustic
      characteristics of males' songs. Studies often investigate song preferences by
      priming females with estrogen. However, estrogenic influences on song preferences
      have not been studied. We investigated the relative influence of early auditory
      experience, acoustic features of songs, and estrogen availability on song
      responsiveness in female zebra finches. Juvenile female zebra finches were
      tutored for 10 days with 40 songs per day with one of three acoustically
      different song types--simple songs, long-bout songs or complex songs. A fourth
      group of females was untutored. Aside from this brief song exposure, females were
      raised and maintained without exposure to male songs. During adulthood, females'
      behavioral responses to the three song types were tested under three hormone
      conditions--untreated, estradiol-treated and 1,4,6-androstatriene-3,17-dione
      (ATD)-treated (to lower endogenous estrogen). Based on the results of our study,
      four conclusions can be drawn. First, song responsiveness in female zebra finches
      is strongly affected by minimal early acoustic experience. Second, inexperienced
      female zebra finches are inherently biased to respond more to complex songs over
      other song types Third, although female zebra finches are inherently biased to
      respond more to complex songs, early acoustic experience may either reinforce or
      weaken this inherent responsiveness to complex songs. Fourth, estrogen
      selectively accentuates song responsiveness in acoustically-experienced female
      zebra finches.

PMID- 18804475
TI  - Molecular cloning and expression of a functional anti-inflammatory protein, Sj16,
      of Schistosoma japonicum.
AB  - Schistosomes are the causative agent of schistosomiasis. In the infected host,
      significant inflammatory response to the parasite is not observed. Previous
      studies of Schistosoma mansoni showed that this subdued inflammatory response was
      due to a 16-kDa protein, Sm16, which is present in high levels in the secretions
      of schistosomula. Here we report the cloning and characterization of a gene
      (named Sj16) from Schistosoma japonicum. Sequence analysis showed that Sj16
      shares 99% identity with Sm16 in its nucleotide sequence, and 100% identity in
      its protein sequence. While previous studies reportedly failed to obtain the
      soluble recombinant protein of Sm16, we expressed and purified recombinant Sj16
      (rSj16) from Escherichia coli. Western blot and ELISA analyses showed that S.
      japonicum-infected rabbit sera could not recognize rSj16, indicating that native
      Sj16 may fail to induce circulating antibodies during S. japonicum infection. In
      vivo, rSj16 dramatically suppressed the recruitment of thioglycollate-mediated
      leukocytes to the peritoneal cavity of BALB/c mice, accompanied by marked up
      regulation of IL-10 and IL-1RA transcripts, and down-regulation of IL-12p35, IL-1
      beta and MIP-2 transcripts in peritoneal cells. Further analysis revealed that
      rSj16 also suppressed thioglycollate-induced peritoneal macrophage maturation.
      These results demonstrate that rSj16 has an anti-inflammatory function.

PMID- 18804476
TI  - Molecular cloning and characterization of a juvenile hormone esterase gene from
      brown planthopper, Nilaparvata lugens.
AB  - Juvenile hormone (JH) plays key roles in the regulation of growth, development,
      diapause and reproduction in insects, and juvenile hormone esterase (JHE) plays
      an important role in regulating JH titers. We obtained a full-length cDNA
      encoding JHE in Nilaparvata lugens (NlJHE), the first JHE gene cloned from the
      hemipteran insects. The deduced protein sequence of Nljhe contains the five
      conserved motifs identified in JHEs of other insect species, including a
      consensus GQSAG motif that is required for the enzymatic activity of JHE
      proteins. Nljhe showed high amino acid similarities with Athalia rosae JHE (40%)
      and Apis mellifera JHE (39%). Recombinant NlJHE protein expressed in the
      baculovirus expression system hydrolyzed [3H] JH III at high activity and yielded
      the specificity constants (kcat/KM=4.28x10(6) M(-1) s(-1)) close to those of the
      validated JHEs from other insect species, indicating that Nljhe cDNA encodes a
      functional JH esterase. The Nljhe transcript was expressed mainly in the fat body
      and the expression level reached a peak at 48 h after ecdysis of the 5th instar
      nymphs. In the 5th instar, macropterous insects showed significantly higher Nljhe
      mRNA levels and JHE activities, but much lower JH III levels, than those detected
      in the brachypterous insects soon after ecdysis and at 48 h after ecdysis. These
      data suggest that NlJHE might play important roles in regulation of JH levels and
      wing form differentiation.

PMID- 18804477
TI  - Differential expression of two small Hsps during diapause in the corn stalk borer
      Sesamia nonagrioides (Lef.).
AB  - We isolated and characterized two members of the alpha-crystallin/sHsp family,
      SnoHsp19.5 and SnoHsp20.8 from Sesamia nonagrioides (Lepidoptera: Noctuidae). The
      cDNAs encoded proteins of 174 and 185 amino acids, with calculated molecular
      weights of 19.5 and 20.8 kDa, respectively. The deduced amino acid sequences of
      SnoHsp19.5 and SnoHsp20.8 showed highest homology to Hsp19.7 of Mamestra
      brassicae and to Bombyx mori Hsp20.4, respectively. Expression patterns of
      SnoHsp19.5 and SnoHsp20.8 in non-diapausing individuals under different
      environmental conditions (heat or cold) showed different accumulation profiles
      for the two genes after heat and cold treatment. SnoHsp19.5 was consistently
      expressed, while SnoHsp20.8 gene was down-regulated in deep diapause and was up
      regulated at the termination of diapause. Our results suggest that these two
      genes play distinctive roles in the regulation of diapause.

PMID- 18804478
TI  - Mast cells and epsilonPKC: a role in cardiac remodeling in hypertension-induced
      heart failure.
AB  - Heart failure (HF) is a chronic syndrome in which pathological cardiac remodeling
      is an integral part of the disease and mast cell (MC) degranulation-derived
      mediators have been suggested to play a role in its progression. Protein kinase C
      (PKC) signaling is a key event in the signal transduction pathway of MC
      degranulation. We recently found that inhibition of epsilonPKC slows down the
      progression of hypertension-induced HF in salt-sensitive Dahl rats fed a high
      salt diet. We therefore determined whether epsilonPKC inhibition affects MC
      degranulation in this model. Six week-old male Dahl rats were fed with a high
      salt diet to induce systemic hypertension, which resulted in concentric left
      ventricular hypertrophy at the age of 11 weeks, followed by myocardial dilatation
      and HF at the age of 17 weeks. We administered epsilonV1-2, an epsilonPKC
      selective inhibitor peptide (3 mg/kg/day), deltaV1-1, a deltaPKC-selective
      inhibitor peptide (3 mg/kg/day), TAT (negative control; at equimolar
      concentration; 1.6 mg/kg/day) or olmesartan (angiotensin receptor blocker [ARB]
      as a positive control; 3 mg/kg/day) between 11 weeks and 17 weeks. Treatment with
      epsilonV1-2 attenuated cardiac MC degranulation without affecting MC density,
      myocardial fibrosis, microvessel patency, vascular thickening and cardiac
      inflammation in comparison to TAT- or deltaV1-1-treatment. Treatment with ARB
      also attenuated MC degranulation and cardiac remodeling, but to a lesser extent
      when compared to epsilonV1-2. Finally, epsilonV1-2 treatment inhibited MC
      degranulation in isolated peritoneal MCs. Together, our data suggest that
      epsilonPKC inhibition attenuates pathological remodeling in hypertension-induced
      HF, at least in part, by preventing cardiac MC degranulation.

PMID- 18804479
TI  - Reconstituting initial events during the assembly of apolipoprotein B-containing
      lipoproteins in a cell-free system.
AB  - The synthesis of apolipoprotein B (apoB) dictates the formation of chylomicrons
      and very low-density lipoproteins, two major lipoprotein precursors in the human
      plasma. Despite its biological significance, the mechanism of the assembly of
      these apoB-containing lipoproteins remains elusive. An essential obstacle is the
      lack of systems that allow fine dissection of key components during assembly,
      including nascent apoB peptide, lipids in defined forms, chaperones, and
      microsomal triglyceride transfer protein (MTP). In this study, we used a
      prokaryotic cell-free expression system to reconstitute early events in the
      assembly of apoB-containing lipoprotein that involve the N-terminal domains of
      apoB. Our study shows that N-terminal domains larger than 20.5% of apoB (B20.5)
      have an intrinsic ability to remodel vesicular phospholipid bilayers into
      discrete protein-lipid complexes. The presence of appropriate lipid substrates
      during apoB translation plays a pivotal role for successful lipid recruitment,
      and similar lipid recruitment fails to occur if the lipids are added
      posttranslationally. Cotranslational presence of MTP can dramatically promote the
      folding of B6.4-20.5 and B6.4-22. Furthermore, apoB translated in the presence of
      MTP retains its phospholipid recruitment capability posttranslationally. Our data
      suggest that during the synthesis of apoB, the N-terminal domain has a short
      window for intrinsic phospholipid recruitment, the time frame of which is
      predetermined by the environment where apoB synthesis occurs. The presence of MTP
      prolongs this window of time by acting as a chaperone. The absence of either
      proper lipid substrate or MTP may result in the improper folding of apoB and,
      consequently, its degradation.

PMID- 18804480
TI  - Changes in the molecular packing of fibrillin microfibrils during extension
      indicate intrafibrillar and interfibrillar reorganization in elastic response.
AB  - Fibrillin-rich microfibrils are the major structural components of the
      extracellular matrix that provide elasticity in a majority of connective tissues.
      The basis of elastic properties lies in the organization of fibrillin molecules,
      which, unfortunately, is still poorly understood. An X-ray diffraction study of
      hydrated fibrillin-rich microfibrils from zonular filaments has been conducted to
      give an insight into the molecular structure of microfibrils in intact tissue. A
      series of measurements was taken during controlled tissue extension to observe
      alterations in the lateral packing of microfibrils. Computer-generated simulated
      patterns were used to fit the experimental X-ray scattering data and to obtain
      the fibril diameter and lateral distance between the fibrils. The results suggest
      a nonlinear correlation between external strain and decrease in fibril diameter
      and lateral spacing. This was accompanied by a nonlinear increase in axial
      periodicity and a structure with a 160-nm periodicity, which is reported here for
      the first time using X-ray diffraction. These changes may reflect the unraveling
      of fibrillin from the complex folded arrangement into a linear structure. This
      finding supports a pleating model where fibrillin molecules are highly folded
      within the microfibrils; more importantly, the connection is made between the
      interaction of individual microfibrils and the change in their suprafibrillar
      coherent organization during extension. We suggest that the intermediate states
      observed in our study reflect sequential unfolding of fibrillin and can explain
      the process of its reversible unraveling.

PMID- 18804481
TI  - Solution structure and characterization of the DNA-binding activity of the B3BP
      Smr domain.
AB  - The MutS1 protein recognizes unpaired bases and initiates mismatch repair, which
      are essential for high-fidelity DNA replication. The homologous MutS2 protein
      does not contribute to mismatch repair, but suppresses homologous recombination.
      MutS2 lacks the damage-recognition domain of MutS1, but contains an additional C
      terminal extension: the small MutS-related (Smr) domain. This domain, which is
      present in both prokaryotes and eukaryotes, has previously been reported to bind
      to DNA and to possess nicking endonuclease activity. We determine here the
      solution structure of the functionally active Smr domain of the Bcl3-binding
      protein (also known as Nedd4-binding protein 2), a protein with unknown function
      that lacks other domains present in MutS proteins. The Smr domain adopts a two
      layer alpha-beta sandwich fold, which has a structural similarity to the C
      terminal domain of IF3, the R3H domain, and the N-terminal domain of DNase I. The
      most conserved residues are located in three loops that form a contiguous,
      exposed, and positively charged surface with distinct sequence identity for
      prokaryotic and eukaryotic Smr domains. NMR titration experiments and DNA binding
      studies using Bcl3-binding protein-Smr domain mutants suggested that these most
      conserved loop regions participate in DNA binding to single-stranded/double
      stranded DNA junctions. Based on the observed DNA-binding-induced
      multimerization, the structural similarity with both subdomains of DNase I, and
      the experimentally identified DNA-binding surface, we propose a model for DNA
      recognition by the Smr domain.

PMID- 18804482
TI  - A two-age-classes dengue transmission model.
AB  - In this paper, we discuss a two-age-classes dengue transmission model with
      vaccination. The reason to divide the human population into two age classes is
      for practical purpose, as vaccination is usually concentrated in one age class.
      We assume that a constant rate of individuals in the child-class is vaccinated.
      We analyze a threshold number which is equivalent to the basic reproduction
      number. If there is an undeliberate vaccination to infectious children, which
      worsens their condition as the time span of being infectious increases, then
      paradoxically, vaccination can be counter productive. The paradox, stating that
      vaccination makes the basic reproduction number even bigger, can occur if the
      worsening effect is greater than a certain threshold, a function of the human
      demographic and epidemiological parameters, which is independent of the level of
      vaccination. However, if the worsening effect is to increase virulence so that
      one will develop symptoms, then the vaccination is always productive. In both
      situations, screening should take place before vaccination. In general, the
      presence of class division has obscured the known rule of thumb for vaccination.

PMID- 18804483
TI  - WITHDRAWN: The evidence that the fovea is split, and that this has consequences
      for the way we recognise written words.
AB  - This article has been withdrawn consistent with Elsevier Policy on Article
      Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). The Publisher
      apologizes for any inconvenience this may cause.

PMID- 18804484
TI  - Synthesis of ponasterone A derivatives with various steroid skeleton moieties and
      evaluation of their binding to the ecdysone receptor of Kc cells.
AB  - A series of ponasterone A (PNA) derivatives with various steroid moieties were
      synthesized to measure their binding activity to the ecdysone receptors of
      Drosophila Kc cells. The activity of compounds was evaluated by determining the
      concentration required to give the 50% inhibition (IC(50) in M) of the
      incorporation of [(3)H]PNA to Drosophila Kc cells. Compounds with no functional
      groups such as OH and CO group in the steroid skeleton moiety were inactive. By
      the introduction of functional groups such as the OH and the CO group in the
      steroidal structure, these compounds became active. Some compounds containing the
      A/B-trans ring fusion, which is different from that (A/B-cis) of ecdysteroids
      were also active. The oxidation of CH(2) at 6-position to CO, enhanced the
      activity 19 times, but the activity was erased by the reduction of oxo to OH
      group at 6-position. The activity was enhanced about 250 times by the conversion
      of A/B ring configuration from trans [(20R,22R)-2beta,3beta,20,22-tetrahydroxy
      5alpha-cholestan-6-one: pIC(50)=4.84] to cis [(20R,22R)-2beta,3beta,20,22
      tetrahydroxy-5beta-cholestan-6-one: pIC(50)=7.23]. The latter cis-type compound
      which is the most potent among compounds synthesized in this study was equipotent
      to the natural molting hormone, 20-hydroxyecdysone, even though it is 1/50 of
      PNA.

PMID- 18804485
TI  - Genetic drift on networks: ploidy and the time to fixation.
AB  - Genetic drift in finite populations ultimately leads to the loss of genetic
      variation. This paper examines the rate of neutral gene loss for a range of
      population structures defined by a graph. We show that, where individuals reside
      at fixed points on an undirected graph with equal degree nodes, the mean time to
      loss differs from the panmictic value by a positive additive term that depends on
      the number of individuals (not genes) in the population. The effect of these
      spatial structures is to slow the time to fixation by an amount that depends on
      the way individuals are distributed, rather than changing the apparent number of
      genes available to be sampled. This relationship breaks down, however, for a
      broad class of spatial structures such as random, small-world and scale-free
      networks. For the latter structures there is a counter-intuitive acceleration of
      fixation proportional to the level of ploidy.

PMID- 18804486
TI  - Viewpoint invariance in the discrimination of upright and inverted faces.
AB  - Current models of face processing support an orientation-dependent expert face
      processing mechanism. However, even when upright, faces are encountered from
      different viewpoints, across which a face processing system must be able to
      generalize. Different computational models have generated competing predictions
      of how viewpoint variation might affect the perception of upright versus inverted
      faces. Our goal was to examine the interaction between viewpoint variation and
      orientation on face discrimination. Sixteen normal subjects performed an oddity
      paradigm requiring subjects to discriminate changes in three simultaneously
      viewed morphed faces presented either upright or inverted. In one type of trial
      all the faces were seen in frontal view; in the other all faces varied in
      viewpoint, rotated 45 degrees from each other. After the effects of orientation
      were adjusted for perceptual difficulty, there were only main effects of
      orientation and viewpoint, with no interaction between orientation and viewpoint.
      We conclude that the effects of viewpoint variation on the perceptual
      discrimination of faces is not different for upright versus inverted faces,
      indicating that its effects are independent of the expertise that exists for
      upright faces.

PMID- 18804487
TI  - Cocaine conditioning: reversal by autoreceptor dose levels of 8-OHDPAT.
AB  - In order to investigate the contribution of serotonergic effects of cocaine to
      Pavlovian conditioning of cocaine locomotor stimulant effects, two experiments
      were conducted in which groups of rats (N=10) received cocaine treatments (10
      mg/kg) paired or unpaired to placement in an open-field environment. Initially, a
      cocaine conditioned locomotion stimulant effect was established. Next, additional
      Coc-P and Coc-UP pairings were carried out in conjunction with pretreatment
      injections of the 5-HT1A agonist, 8-OHDPAT (0.01, 0.025 and 0.05 mg/kg) or
      saline. In experiment 1, the Coc-P group which received the saline pretreatment
      again exhibited conditioning but in the 8-OHDPAT pretreatment Coc-P group
      conditioning was eliminated. In the second experiment, the protocol of the first
      experiment was repeated but expanded in the post-conditioning phase to include an
      8-OHDPAT plus the 5-HT1A antagonist pretreatment Coc-P group. As in the first
      experiment, the 8-OHDPAT pretreatment Coc-P group did not exhibit a cocaine
      conditioned locomotion stimulant effect; whereas, the saline pretreatment Coc-P
      and the 8-OHDPAT plus WAY-100635 pretreatment Coc-P groups did exhibit the
      cocaine conditioned locomotion stimulant effect. These findings are consistent
      with an important role for serotonin in the maintenance of cocaine Pavlovian
      conditioned effects.

PMID- 18804488
TI  - Immunoglobulins, antibody repertoire and B cell development.
AB  - Swine share with most placental mammals the same five antibody isotypes and same
      two light chain types. Loci encoding lambda, kappa and Ig heavy chains appear to
      be organized as they are in other mammals. Swine differ from rodents and
      primates, but are similar to rabbits in using a single VH family (VH3) to encode
      their variable heavy chain domain, but not the family used by cattle, another
      artiodactyl. Distinct from other hoofed mammals and rodents, Ckappa:Clambda usage
      resembles the 1:1 ratio seen in primates. Since IgG subclasses diversified after
      speciation, same name subclass homologs do not exist among swine and other
      mammals unless very closely related. Swine possess six putative IgG subclasses
      that appear to have diversified by gene duplication and exon shuffle while
      retaining motifs that can bind to FcgammaRs, FcRn, C1q, protein A and protein G.
      The epithelial chorial placenta of swine and the precosial nature of their
      offspring have made piglets excellent models for studies on fetal antibody
      repertoire development and on the postnatal role of gut colonization, maternal
      colostrum and neonatal infection on the development of adaptive immunity during
      the "critical window" of immunological development. This chapter traces the study
      of the humoral immune system of this species through its various eras of
      discovery and compiles the results in tables and figures that should be a useful
      reference for educators and investigators.

PMID- 18804489
TI  - The role of PEI structure and size in the PEI/liposome-mediated synergism of gene
      transfection.
AB  - Polyethylenimines (PEIs) and cationic liposomes are widely used for nonviral gene
      delivery. When PEIs have been used alone, the transfection efficiency has been
      higher for larger or linear than smaller or branched PEIs. We have reported
      previously that a combination of small PEIs and liposomes results in a
      potentiation of transfection efficiency in vitro. Here, the role of PEI size and
      structure in this synergism has been clarified further. Therefore, two
      structurally different high MW PEIs, i.e. the linear PEI22K and branched PEI25K,
      were studied in the SMC cells. We found that both linear PEI22K and branched
      PEI25K resulted in a similar synergism and comparable transfection efficiencies.
      However, the potentiation for larger PEIs found in the present study was weaker
      than that for smaller PEIs obtained in our previous studies. In conclusion, our
      present and previous results demonstrate that the increment of PEI/liposome
      mediated gene transfection by different types of PEIs in vitro is a common
      attribute that is rather associated with their size than the structure.
      Interestingly, the effect of PEI size seems to be opposite when combined with
      liposome or given alone, i.e. the small PEIs are more effective when combined and
      less effective when alone than the larger ones.

PMID- 18804490
TI  - The underestimated role of olfaction in avian reproduction?
AB  - Until the second half of the 20th century, it was broadly accepted that most
      birds are microsmatic if not anosmic and unable to detect and use olfactory
      information. Exceptions were eventually conceded for species like
      procellariiforms, vultures or kiwis that detect their food at least in part based
      on olfactory signals. During the past 20-30 years, many publications have
      appeared indicating that this view is definitely erroneous. We briefly review
      here anatomical, electrophysiological and behavioral data demonstrating that
      birds in general possess a functional olfactory system and are able to use
      olfactory information in a variety of ethological contexts, including
      reproduction. Recent work also indicates that brain activation induced by sexual
      interactions with a female is significantly affected by olfactory deprivation in
      Japanese quail. Brain activation was measured via immunocytochemical detection of
      the protein product of the immediate early gene c-fos. Changes observed concerned
      two brain areas that play a key role in the control of male sexual behavior, the
      medial preoptic nucleus and the bed nucleus of the stria terminalis therefore
      suggesting a potential role of olfaction in the control of reproduction. The
      widespread idea that birds are anosmic or microsmatic is thus not supported by
      the available experimental data and presumably originates in our anthropomorphic
      view that leads us to think that birds do not smell because they have a rigid
      beak and nostrils and do not obviously sniff. Experimental analysis of this
      phenomenon is thus warranted and should lead to a significant change in our
      understanding of avian biology.

PMID- 18804491
TI  - Role of the rat gastrointestinal mucosa in catabolism of endothelin peptides.
AB  - Endothelin-1 is involved in physiology and pathophysiology of the alimentary
      tract. The peptide modulates blood flow in the gastrointestinal microvasculature
      and regulates contractility of smooth muscles and, when present in excess, may be
      an important factor contributing to pathogenesis of various forms of mucosal
      injury and peristaltic disorders. Mechanisms that regulate endothelin
      concentration in the gastrointestinal tissues are unknown. Therefore, the aim of
      our study was to identify and characterize endothelin inactivating peptidases in
      the rat gastrointestinal mucosa and smooth muscle cells. We have found three high
      affinity and efficient endothelin-1 inactivating peptidases. The acidic (pH
      optimum 5.5), membrane-bound, thiorphan- (ED(50) 1.2+/-0.2 nM) and phosphoramidon
      (ED(50) 150+/-25 pM) sensitive, endothelin-1 inactivating peptidase (K(M) 0.12+/
      0.03 microM) was present in the mucosal cells of duodenum and small intestine.
      The enzyme exhibited high molecular weight (>100 kDa) and characteristics similar
      to that of the rat and human kidney, acidic metalloendopeptidase that was
      recently described. Two forms of the unique, low molecular weight (100>MW>30
      kDa), alkaline (pH optimum 8.5), specific (K(M) 0.5+/-0.2 microM), thiorphan- and
      phosphoramidon insensitive, 1,10 phenanthroline inhibitable (ED(50) 0.65+/-0.20
      mM, mean+/-S.E.M.) endothelin-1 inactivating peptidase were present exclusively
      in the duodenal mucosal cells; soluble form in cytosol and membrane-bound form
      exhibiting an abundance ratio 5:1, respectively. Mucosa of the stomach and large
      intestine, and gastrointestinal smooth muscle cells do not contain the specific
      endothelin-1 inactivating peptidases. The enzymes may play a crucial role in
      regulation of endothelin concentration in the gastrointestinal tissues. Whether
      impairment of activity of the mucosal endothelin inactivating peptidases,
      resulting in the increase of concentration of endothelin peptides in
      gastrointestinal tissues, occurs in various pathological conditions is actually
      studied in our laboratory.

PMID- 18804492
TI  - Vagotomy and accompanying pyloroplasty down-regulates ghrelin mRNA but does not
      affect ghrelin secretion.
AB  - In this study, we have examined how the lack of vagus activity affects the long
      term secretion of total and active ghrelin. We subjected mice to sham-operation,
      pyloroplasty or vagotomy and pyloroplasty. The study lasted for 2 weeks, during
      which body weight development and daily food intake was monitored. At the end of
      the study, the mice were sacrificed, and serum and fundus were collected.
      Measurements of total and active serum ghrelin revealed no difference between the
      surgical groups and sham-operated mice, despite the fact that fundic ghrelin mRNA
      was down-regulated. The results presented here suggest that the vagus activity is
      not required for the long-term secretion of neither total nor active ghrelin in
      mice. They also suggest that fundic ghrelin mRNA expression is affected by
      pyloroplasty and vagotomy but that this effect does not translate into changes in
      ghrelin levels in the circulation.

PMID- 18804493
TI  - Effect of exendin-4 treatment upon glucose uptake parameters in rat liver and
      muscle, in normal and type 2 diabetic state.
AB  - Exendin-4, like GLP-1, is insulinotropic, antidiabetic and glucoregulatory among
      other properties, which are thought to be exerted through the pancreatic GLP-1
      receptor; exendin-4 is also an agonist of the GLP-1 stimulatory action upon liver
      and muscle glucose metabolism, where GLP-1 receptor is distinct from that in the
      pancreas. We investigated the action of prolonged treatment with exendin-4 upon
      glucose transport parameters in skeletal muscle and liver of normal rats and
      streptozotocin-induced type 2 diabetic rats (T2D). Muscle of T2D showed lower
      than normal glucose transport; exendin-4 did not modify the value in normal but
      normalized that in the T2D; unlike previously detected with GLP-1, no apparent
      modification was observed in GLUT-4 expression in either group after exendin-4,
      except for an increased GLUT-4 protein in normal rats. Yet, exendin-4
      significantly stimulated liver GLUT-2-mRNA and -protein in T2D and normal rats,
      the effect upon GLUT-2-protein in T2D being higher than that in normal animals;
      this was accompanied by a normalizing action of exendin-4 upon the lower than
      normal liver glycogen in T2D rats. These data suggest that the liver may
      represent at least one of the major target organs for exendin-4 to exert its
      plasma lowering effect in diabetic state.

PMID- 18804494
TI  - BRCA1 is regulated by Chk2 in response to spindle damage.
AB  - Inherited mutations of the breast cancer susceptibility gene 1 (BRCA1) confer an
      increased risk for breast, ovarian and prostate cancer. BRCA1 has been involved
      in regulation of cell cycle progression, DNA damage signaling and repair,
      maintenance of genome integrity, ubiquitination and regulation of transcription.
      Aside from its essential functions in the DNA damage response BRCA1 has been also
      involved in the cellular response to microtubule damage. Emerging evidence
      indicates that BRCA1 regulates the duplication and the function of centrosomes,
      participates in mitotic spindle assembly and is required in the spindle
      checkpoint. Given BRCA1 distinct functions in microtubule-dependent pathways, we
      hypothesized that BRCA1 might be regulated following microtubule damage. In the
      present study, we report the novel finding that BRCA1 is phosphorylated by the
      checkpoint kinase Chk2 on the previously identified site Ser988 following anti
      mitotic treatment in human cancer cells. Ser988-phosphorylated BRCA1 accumulates
      at centrosomes in response to microtubule damage but Ser988 is not essential for
      BRCA1 localization at the microtubule-organizing centers. We further demonstrate
      that the Ser988 phosphorylation is important for the inhibiting microtubule
      nucleation activity of BRCA1 and for BRCA1 function in cell survival following
      microtubule damage. These findings reveal a striking outcome of BRCA1
      phosphorylation by Chk2 on its role in microtubule-dependent pathways and suggest
      a fine cross-talk between DNA damage and spindle damage responses.

PMID- 18804495
TI  - Time-frequency-topographic analysis of induced power and synchrony of EEG signals
      during a Go/No-Go task.
AB  - Induced changes in electroencephalographic power and synchrony between pairs of
      electrodes were assessed during the Go/No-Go task in 15 young adults. Processes
      common to both conditions, such as attention, activation of working memory,
      letter identification, and discrimination processes were characterized by
      increased power and synchrony in the following frequency ranges: delta band
      (inhibition of the non-relevant stimuli), theta band (activation of working
      memory), and low alpha band in occipital regions immediately after the stimulus
      (withhold or control of the execution of a response), and decreased power in the
      high alpha band from 300 to 700 ms. However, the most important findings were
      those specific for each condition. Changes in power in frontal areas were
      observed immediately after the stimulus in delta and high alpha bands for the Go
      condition and in the theta band for the No-Go condition. Increased synchrony and
      power at 1 Hz from 350-500 ms and increased power at 1, 5 and 6 Hz after 300 ms
      in the No-Go condition may be related to inhibition. Other important difference
      between conditions was observed in the synchronization increases of the gamma
      band between 33 and 36 Hz in the Go condition, whereas synchrony decreased at
      these frequencies in the No-Go condition; these differences may be due to the
      preparation and execution of the motor response during the Go condition and its
      inhibition in the No-Go condition.

PMID- 18804496
TI  - Electrophysiological evidence for early non-conscious processing of fearful
      facial expressions.
AB  - Non-conscious processing of emotionally expressive faces has been found in
      patients with damage to visual brain areas and has been demonstrated
      experimentally in healthy controls using visual masking procedures. The time at
      which this subliminal processing occurs is not known. To address this question, a
      group of healthy participants performed a fearful face detection task in which
      backward masked fearful and non-fearful faces were presented at durations ranging
      from 16 to 266 ms. On the basis of the group's behavioural results, high-density
      event-related potentials were analysed for subliminal, intermediate and
      supraliminal presentations. Subliminally presented fearful faces were found to
      produce a stronger posterior negativity at 170 ms (N170) than non-fearful faces.
      This increase was also observed for intermediate and supraliminal conditions. A
      later component, the N2 occurring between 260 and 300 ms, was the earliest
      component related to stimulus detectability, increasing with target duration and
      differentiating fearful from non-fearful faces at longer durations of
      presentation. Source localisation performed on the N170 component showed that
      fear produced a greater activation of extrastriate visual areas, particularly on
      the right. Whether they are presented subliminally or supraliminally, fearful
      faces are processed at an early stage in the stream of visual processing, giving
      rise to enhanced activation of right extrastriate temporal cortex as early as 170
      ms post-stimulus onset.

PMID- 18804497
TI  - Association analysis of nuclear receptor Rev-erb alpha gene (NR1D1) with mood
      disorders in the Japanese population.
AB  - Several investigations have suggested that alterations in circadian rhythms may
      lay the foundation for the development of mood disorder (bipolar disorder and
      major depressive disorder). Recently, the nuclear receptor Rev-erb alpha was
      reported to be related to circadian rhythms, and was shown to be involved in the
      biological action of lithium in vitro. These evidences indicate that the nuclear
      receptor Rev-erb alpha gene (NR1D1) is a good candidate gene for the pathogenesis
      of mood disorders. To evaluate the association between NR1D1 and mood disorders,
      we conducted a case-control study of Japanese samples (147 bipolar patients, 322
      major depressive disorder patients and 360 controls) with three tagging SNPs
      selected by HapMap database. One SNP showed an association with bipolar disorder
      in females. After Bonferroni correction for multiple testing, however, this
      significance disappeared. No significant association was found with major
      depressive disorder. In conclusion, our findings suggest that NR1D1 does not play
      a major role in the pathophysiology of mood disorders in the Japanese population.

PMID- 18804498
TI  - Subcellular localization of the triple gene block proteins encoded by a
      Foveavirus infecting grapevines.
AB  - Grapevine rupestris stem pitting-associated virus (GRSPaV; Foveavirus;
      Flexiviridae) contains a positive-sense, ssRNA genome. GRSPaV occurs worldwide in
      grapes and is involved in the Rugose Wood disease complex. The GRSPaV genome
      contains the triple gene block (TGB), a genetic module present in several genera
      of plant RNA viruses. TGB encodes three proteins (TGBp1, TGBp2 and TGBp3) that
      are believed to work together to achieve intra- and inter-cellular transport of
      virions in infected plants. To reveal the subcellular localization of each TGB
      protein and to examine the impact that different fusion positions may have on the
      behavior of the native protein, we made a series of expression constructs and
      expressed the corresponding protein fusions in Nicotiana tabacum BY-2 cells and
      protoplasts. We demonstrated that TGBp1 had both a cytosolic and nuclear
      distribution. Two TGBp1 fusions (GFP fused at the N- or C-terminus) differ in
      subcellular distribution. Through the use of truncation mutants, we mapped TGBp1
      regions responsible for the formation of two distinct types of aggregates.
      Sequence analyses predicted two and one transmembrane domains in TGBp2 and TGBp3,
      respectively. GFP fusions at either terminus of TGBp2 revealed identical
      localization to the ER network and ER-derived structures. In contrast, the two
      TGBp3 fusions to mRFP differed in localization. This is the first report on the
      subcellular localization of the viral proteins of a member of the Foveavirus
      genus.

PMID- 18804499
TI  - Delivery of siRNA into the cytoplasm by liposomal bubbles and ultrasound.
AB  - Small interfering RNA (siRNA) is expected to be a novel therapeutic tool,
      however, its utilization has been limited by inefficient delivery systems.
      Recently, we have developed novel polyethyleneglycol modified liposomes (Bubble
      liposomes; BL) entrapping an ultrasound (US) imaging gas, which can work as a
      gene delivery tool with US exposure. In this study, we investigated whether the
      BL were suitable for the delivery of siRNA. BL efficiently delivered siRNA with
      only 10 s of exposure to US in vitro. Specific gene silencing effects could be
      achieved well even in the presence of serum or with the disruption of
      endocytosis. We suggest that siRNA is directly introduced into the cytoplasm by
      the BL and US and the mechanism enables effective transfection within a short
      time and in the presence of high serum. Transfection of siRNA into the tibialis
      muscles with BL and US was also performed. The gene-silencing effect could be
      sustained for more than 3 weeks. Thus, BL could be a useful siRNA delivery tool
      in vitro and in vivo.

PMID- 18804500
TI  - Peptidomic analysis of blood plasma after in vivo treatment with protease
      inhibitors--a proof of concept study.
AB  - Native peptides can be regarded as surrogate markers for protease activity in
      biological samples. Analysis of peptides by peptidomics allows to monitor
      protease activity in vivo and to describe the influence of protease inhibition.
      To elucidate the potential of peptides as markers for in vivo protease inhibition
      we analyzed plasma samples from animals treated with either the indirect FXa
      inhibitor FONDAPARINUX or the dipeptidylpeptidase IV inhibitor AB192. Signals
      correlating with the treatment were subsequently identified and assessed with
      respect to protease-dependent consensus cleavage motifs and occurrence of
      downstream targets. It could be shown that regulated peptides were either
      substrates, products or downstream targets of the inhibited protease. The results
      from the present study demonstrate that the in vivo analysis of peptides by
      peptidomics has the potential to broaden the knowledge of inhibitor related
      effects in vivo and that this method may pave the way to develop predictive
      biomarkers.

PMID- 18804501
TI  - CB(2) cannabinoid receptor antagonist SR144528 decreases mu-opioid receptor
      expression and activation in mouse brainstem: role of CB(2) receptor in pain.
AB  - Formerly considered as an exclusively peripheral receptor, it is now accepted
      that CB(2) cannabinoid receptor is also present in limited amounts and distinct
      locations in the brain of several animal species, including mice. However, the
      possible roles of CB(2) receptors in the brain need to be clarified. The aim of
      our work was to study the mu-opioid receptor (MOR) mRNA expression level and
      functional activity after acute in vivo and in vitro treatments with the
      endocannabinoid noladin ether (NE) and with the CB(2) receptor antagonist
      SR144528 in brainstem of mice deficient in either CB(1) or CB(2) receptors. This
      study is based on our previous observations that noladin ether (NE) produces
      decrease in the activity of MOR in forebrain and this attenuation can be
      antagonized by the CB(2) cannabinoid antagonist SR144528, suggesting a CB(2)
      receptor mediated effect. We used quantitative real-time PCR to examine the
      changes of MOR mRNA levels, [(35)S]GTPgammaS binding assay to analyze the
      capability of mu-opioid agonist DAMGO to activate G-proteins and competition
      binding assays to directly measure the ligand binding to MOR in mice brainstem.
      After acute NE administration no significant changes were observed on MOR
      signaling. Nevertheless pretreatment of mice with SR144528 prior to the
      administration of NE significantly decreased MOR signaling suggesting the
      involvement of SR144528 in mediating the effect of MOR. mRNA expression of MORs
      significantly decreased both in CB(1) wild-type and CB(1) knockout mice after a
      single injection of SR144528 at 0.1mg/kg when compared to the vehicle treated
      controls. Consequently, MOR-mediated signaling was attenuated after acute in vivo
      treatment with SR144528 in both CB(1) wild-type and CB(1) knockout mice. In vitro
      addition of 1microM SR144528 caused a decrease in the maximal stimulation of
      DAMGO in [(35)S]GTPgammaS binding assays in CB(2) wild-type brainstem membranes
      whereas no significant changes were observed in CB(2) receptor knockouts.
      Radioligand binding competition studies showed that the noticed effect of
      SR144528 on MOR signaling is not mediated through MORs. Our data demonstrate that
      the SR144528 caused pronounced decrease in the activity of MOR is mediated via
      CB(2) cannabinoid receptors.

PMID- 18804502
TI  - alpha-Synuclein enhances secretion and toxicity of amyloid beta peptides in PC12
      cells.
AB  - alpha-Synuclein is the fundamental component of Lewy bodies which occur in the
      brain of 60% of sporadic and familial Alzheimer's disease patients. Moreover, a
      proteolytic fragment of alpha-synuclein, the so-called non-amyloid component of
      Alzheimer's disease amyloid, was found to be an integral part of Alzheimer's
      dementia related plaques. However, the role of alpha-synuclein in pathomechanism
      of Alzheimer's disease remains elusive. In particular, the relationship between
      alpha-synuclein and amyloid beta is unknown. In the present study we showed the
      involvement of alpha-synuclein in amyloid beta secretion and in the mechanism of
      amyloid beta evoked mitochondria dysfunction and cell death. Rat pheochromocytoma
      PC12 cells transfected with amyloid beta precursor protein bearing Swedish double
      mutation (APPsw) and control PC12 cells transfected with empty vector were used
      in this study. alpha-Synuclein (10microM) was found to increase by twofold
      amyloid beta secretion from control and APPsw PC12 cells. Moreover, alpha
      synuclein decreased the viability of PC12 cells by about 50% and potentiated
      amyloid beta toxicity leading to mitochondrial dysfunction and caspase-dependent
      programmed cell death. Inhibitor of caspase-3 (Z-DEVD-FMK, 100microM), and a
      mitochondrial permeability transition pore blocker, cyclosporine A (2microM)
      protected PC12 cells against alpha-synuclein or amyloid beta evoked cell death.
      In contrast Z-DEVD-FMK and cyclosporine A were ineffective in APPsw cells
      containing elevated amount of amyloid beta treated with alpha-synuclein. It was
      found that the inhibition of neuronal and inducible nitric oxide synthase
      reversed the toxic effect of alpha-synuclein in control but not in APPsw cells.
      Our results indicate that alpha-synuclein enhances the release and toxicity of
      amyloid beta leading to nitric oxide mediated irreversible mitochondria
      dysfunction and caspase-dependent programmed cell death.

PMID- 18804503
TI  - Intranasal and subcutaneous immunization under the effect of estradiol leads to
      better protection against genital HSV-2 challenge compared to progesterone.
AB  - This study examined the effect of hormonal environment on intranasal and
      subcutaneous routes of immunization in a genital herpes infection model.
      Ovariectomized mice were treated with estradiol (E(2)), progesterone (P(4)) or
      placebo hormone pellets and immunized intranasally (i.n.) or subcutaneously
      (s.c.) with attenuated HSV-2. Immunized mice were subsequently challenged,
      intravaginally, with wild-type HSV-2. Mice immunized under the influence of E(2)
      showed higher survival rates, reduced pathology and significantly lower viral
      shedding compared with those immunized under the influence of P(4) or placebo, by
      both i.n. and s.c. routes. Vaginal and serum anti-HSV-2 IgG, but not IgA, levels
      correlated with decreased pathology in E(2)-treated, i.n. immunized mice. We
      conclude that immunization under the influence of E(2) afforded better protection
      compared to placebo and P(4), by both routes of immunization. Female sex hormones
      can influence immune responses and outcome of viral challenge in the genital
      tract following systemic immunization.

PMID- 18804504
TI  - New malaria vaccine candidates based on the Plasmodium vivax Merozoite Surface
      Protein-1 and the TLR-5 agonist Salmonella Typhimurium FliC flagellin.
AB  - The present study evaluated the immunogenicity of new malaria vaccine
      formulations based on the 19kDa C-terminal fragment of Plasmodium vivax Merozoite
      Surface Protein-1 (MSP1(19)) and the Salmonella enterica serovar Typhimurium
      flagellin (FliC), a Toll-like receptor 5 (TLR5) agonist. FliC was used as an
      adjuvant either admixed or genetically linked to the P. vivax MSP1(19) and
      administered to C57BL/6 mice via parenteral (s.c.) or mucosal (i.n.) routes. The
      recombinant fusion protein preserved MSP1(19) epitopes recognized by sera
      collected from P. vivax infected humans and TLR5 agonist activity. Mice
      parenterally immunized with recombinant P. vivax MSP1(19) in the presence of
      FliC, either admixed or genetically linked, elicited strong and long-lasting
      MSP1(19)-specific systemic antibody responses with a prevailing IgG1 subclass
      response. Incorporation of another TLR agonist, CpG ODN 1826, resulted in a more
      balanced response, as evaluated by the IgG1/IgG2c ratio, and higher cell-mediated
      immune response measured by interferon-gamma secretion. Finally, we show that
      MSP1(19)-specific antibodies recognized the native protein expressed on the
      surface of P. vivax parasites harvested from infected humans. The present report
      proposes a new class of malaria vaccine formulation based on the use of malarial
      antigens and the innate immunity agonist FliC. It contains intrinsic adjuvant
      properties and enhanced ability to induce specific humoral and cellular immune
      responses when administered alone or in combination with other adjuvants.

PMID- 18804505
TI  - Comparison of the immunomodulatory effects of L. donovani and L. major excreted
      secreted antigens, particulate and soluble extracts and viable parasites on human
      dendritic cells.
AB  - In an experimental model of human monocyte-derived dendritic cells (DCs), the
      immunophenotype of mature DCs infected with Leishmania donovani and Leishmania
      major showed a weak decrease in the cell surface expression of CD40, CD86, HLA-DR
      and DC-SIGN compared with uninfected control DCs. This immunomodulatory effect
      was more pronounced after stimulation with excreted-secreted antigens (ESA) of
      both species but absent after stimulation with particulate and soluble extracts.
      Infection with viable promastigotes, as well as stimulation with ESA from L.
      donovani and L. major, decreased IL-10 and IL-12p70 secretion. To our knowledge,
      this is the first direct demonstration that ESA from Leishmania promastigotes can
      stimulate DCs in the same manner as viable promastigotes.

PMID- 18804506
TI  - Immune modulating effect by a phosphoprotein-deleted rabies virus vaccine vector
      expressing two copies of the rabies virus glycoprotein gene.
AB  - The type of immune response induced by a vaccine is a critical factor that
      determines its effectiveness in preventing infection or disease. Inactivated and
      live rabies virus (RV) vaccine strains elicit an IgG1-biased and IgG1/IgG2a
      balanced antibody response, respectively. However, IgG2a antibodies are potent
      inducers of anti-viral effector functions, and therefore, a viral vaccine vector
      that can elicit an IgG2a-biased antibody response may be more effective against
      RV infection. Here we describe the humoral immune response of a live replication
      deficient phosphoprotein (P)-deleted RV vector (SPBN-DeltaP), or a recombinant P
      deleted virus that expresses two copies of the RV glycoprotein (G) gene (SPBN
      DeltaP-RVG), and compare it to a UV-inactivated RV. Mice inoculated with UV
      inactivated RV induced predominantly an IgG1-specific antibody response, while
      live recombinant SPBN-DeltaP exhibited a mixed IgG1/IgG2a antibody response,
      which is consistent with the isotype profiles from the replication-competent
      parental viruses. Survivorship in mice after pathogenic RV challenge indicates a
      10-fold higher efficiency of live SPBN-DeltaP compared to UV-inactivated SPBN
      DeltaP. In addition, SPBN-DeltaP-RVG induced a more rapid and robust IgG2a
      response that protected mice more effectively than SPBN-DeltaP. Of note, 10(3)ffu
      of SPBN-DeltaP-RVG-induced anti-RV antibodies that were 100% protective in mice
      against pathogenic RV challenge. The increased immune response was directed not
      only against RV G but also against the ribonucleoprotein (RNP), indicating that
      the expression of two RV G genes from SPBN-DeltaP-RVG enhances the immune
      response to other RV antigens as well. In addition, Rag2 mice inoculated
      intramuscularly with 10(5)ffu/mouse of SPBN-DeltaP showed no clinical signs of
      rabies, and no viral RNA was detected in the spinal cord or brain of inoculated
      mice. Therefore, the safety of the P-deleted vectors along with the onset and
      magnitude of the IgG2a-induced immune response by SPBN-DeltaP-RVG indicate that
      this vector holds great promise as either a therapeutic or preventative vaccine
      against RV or other infectious diseases.

PMID- 18804507
TI  - Rabies awareness in eight Asian countries.
AB  - Rabies is a deadly zoonotic disease most often transmitted to humans through a
      dog bite. Human mortality from endemic canine rabies is estimated by WHO to be
      around 55,000 deaths annually, with over 31,000 deaths in Asia alone, mostly
      children. Most of these deaths could be prevented through post-exposure
      prophylaxis (PEP), including immediate wound washing, rabies immunoglobulin
      administration and vaccination. Unfortunately, at-risk populations are not well
      informed of the risk of rabies and what to do in the event of an animal bite. In
      order to identify the main gaps in rabies information and better define the most
      urgent information actions to be undertaken, the Asian Rabies Expert Bureau
      (AREB) conducted a multicentre, multi-country survey of patients seeking rabies
      post-exposure prophylaxis in rabies prevention centres from 1 July 2007 to 31
      January 2008, in Bangladesh, China, India, Indonesia, Pakistan, the Philippines,
      Sri Lanka, and Thailand. Questionnaires were completed for 4377 subjects in the
      eight countries. Data was collected regarding the patient, former rabies
      exposures, the present wound, rabies exposure management, and rabies awareness.
      Two major issues were identified where active information of the population could
      make a difference: the necessity to apply appropriate wound care and to consult
      the nearest rabies prevention centre as soon as possible.

PMID- 18804508
TI  - Cervical cancer vaccination: the real meaning of cross-protection and its impact
      on the prevention.
AB  - Prophylactic VLP-based vaccines effectively prevent papillomavirus infections
      with a high level of antibodies and safety. An 18% increased efficacy against CIN
      2+ lesions associated with HPVs 16/18 has been observed with the appliance of the
      HPV16/18 AS04 adjuvanted recombinant vaccine.

PMID- 18804509
TI  - Mixed allele malaria vaccines: host protection and within-host selection.
AB  - Malaria parasites are frequently polymorphic at the antigenic targets of many
      candidate vaccines, presumably as a consequence of selection pressure from
      protective immune responses. Conventional wisdom is therefore that vaccines
      directed against a single variant could select for non-target variants, rendering
      the vaccine useless. Many people have argued that a solution is to develop
      vaccines containing the products of more than one variant of the target. However,
      we are unaware of any evidence that multi-allele vaccines better protect hosts
      against parasites or morbidity. Moreover, selection of antigen-variants is not
      the only evolution that could occur in response to vaccination. Increased
      virulence could also be favored if more aggressive strains are less well
      controlled by vaccine-induced immunity. Virulence and antigenic identity have
      been confounded in all studies so far, and so we do not know formally from any
      animal or human studies whether vaccine failure has been due to evasion of
      protective responses by variants at target epitopes, or whether vaccines are just
      less good at protecting against more aggressive strains. Using the rodent malaria
      model Plasmodium chabaudi and recombinant apical membrane antigen-1 (AMA-1), we
      tested whether a bi-allelic vaccine afforded greater protection from parasite
      infection and morbidity than did vaccination with the component alleles alone. We
      also tested the effect of mono- and bi-allelic vaccination on within-host
      selection of mixed P. chabaudi infections, and whether parasite virulence
      mediates pathogen titres in immunized hosts. We found that vaccination with the
      bi-allelic AMA-1 formulation did not afford the host greater protection from
      parasite infection or morbidity than did mono-allelic AMA-1 immunization. Mono
      allelic immunization increased the frequency of heterologous clones in mixed
      clone infections. There was no evidence that any type of immunization regime
      favored virulence. A single AMA-1 variant is a component of candidate malaria
      vaccines current in human trials; our results suggest that adding extra AMA-1
      alleles to these vaccines would not confer clinical benefits, but that that mono
      allelic vaccines could alter AMA-1 allele frequencies in natural populations.

PMID- 18804510
TI  - A pilot study on intradermal vaccination of Japanese rabies vaccine for pre
      exposure immunization.
AB  - Japanese rabies vaccine, a purified chick embryo cell vaccine manufactured by
      Kaketsuken (PCEC-K), is normally given subcutaneously; however, this requires a
      large amount of vaccine, and the pre-exposure vaccination regimen requires 6
      months to complete. These factors often hamper appropriate vaccination.
      Therefore, we examined whether this vaccine could induce adequate level of viral
      neutralizing antibody (VNA) when vaccinated according to the World Health
      Organization (WHO) intradermal regimen. Our pilot study showed that this regimen
      resulted in all subjects developing adequate VNA levels. Intradermal route was
      effective not only for pre-exposure but also for booster vaccination. The
      intradermal PCEC-K regimen was found to be safe and effective in inducing
      adequate VNA levels with the use of a smaller quantity of vaccine and within a
      shorter period of time.

PMID- 18804511
TI  - A statistical model to estimate the impact of a hepatitis A vaccination
      programme.
AB  - A program of routine hepatitis A+B vaccination in preadolescents was introduced
      in 1998 in Catalonia, a region situated in the northeast of Spain. The objective
      of this study was to quantify the reduction in the incidence of hepatitis A in
      order to differentiate the natural reduction of the incidence of hepatitis A from
      that produced due to the vaccination programme and to predict the evolution of
      the disease in forthcoming years. A generalized linear model (GLM) using negative
      binomial regression was used to estimate the incidence rates of hepatitis A in
      Catalonia by year, age group and vaccination. Introduction of the vaccine reduced
      cases by 5.5 by year (p-value<0.001), but there was a significant interaction
      between the year of report and vaccination that smoothed this reduction (p
      value<0.001). The reduction was not equal in all age groups, being greater in the
      12-18 years age group, which fell from a mean rate of 8.15 per 100,000
      person/years in the pre-vaccination period (1992-1998) to 1.4 in the vaccination
      period (1999-2005). The model predicts the evolution accurately for the group of
      vaccinated subjects. Negative binomial regression is more appropriate than
      Poisson regression when observed variance exceeds the observed mean
      (overdispersed count data), can cause a variable apparently contribute more on
      the model of what really makes it.

PMID- 18804512
TI  - Cysteine proteinase type III is protective against Leishmania infantum infection
      in BALB/c mice and highly antigenic in visceral leishmaniasis individuals.
AB  - Visceral leishmaniasis is the most acute form of leishmaniasis and vaccination is
      the best approach to control it. One of the major groups of virulence factors in
      Leishmania belongs to cysteine proteinase family. In this study, for the first
      time, the protective potential of Leishmania infantum cysteine proteinase type
      III (CPC) by using a prime-boost strategy is evaluated in BALB/c mice. The
      experiment was carried out in three groups of mice. Vaccinated group was primed
      with pcDNA-cpc and boosted with rCPC-DHFR in combination with CpG motif and
      Montanide 720 as adjuvant. Control groups received pcDNA and rDHFR or PBS. The
      ratio of IgG2a/IgG1, nitric oxide concentration and IFN-gamma induction in
      vaccinated group is significantly higher than controls. Furthermore, the parasite
      load of vaccinated group is significantly lower than controls. In addition, sera
      reactivity of visceral leishmaniasis individuals was examined and showed
      considerable reactivities toward rCPC in comparison with cutaneous leishmaniasis.
      The achieved result is highly encouraging the use of cysteine proteinases types
      I, II and III as vaccine candidate against visceral leishmaniasis.

PMID- 18804513
TI  - Spearmint induced hypothalamic oxidative stress and testicular anti-androgenicity
      in male rats - altered levels of gene expression, enzymes and hormones.
AB  - Mentha spicata Labiatae, commonly known as spearmint, can be used for various
      kinds of illnesses in herbal medicines and food industries. One of the prominent
      functions of this plant extract is its anti-androgenic activity. The present
      study investigated the probable correlation between oxidative stress in
      hypothalamic region and anti-androgenic action of this plant's aqueous extract on
      rats. Decreased activities of enzymes like superoxide dismutase, catalase,
      glutathione peroxidase and glutathione reductase in hypothalamus of treated rats
      indicated spearmint induced oxidative stress. Further RT-PCR and immunoblot
      analysis demonstrated the decreased expression of some of the steroidogenic
      enzymes, cytochrome P450scc, cytochrome P450C17, 3beta-Hydroxysteroid
      dehydrogenase (3beta-HSD), 17beta-Hydroxysteroid dehydrogenase (17beta-HSD) and
      other related proteins like, steroidogenic acute regulatory protein, androgen
      receptor and scavenger receptor class B-1. Further, in vitro enzyme assays
      demonstrated depressed activities of testicular 3beta-HSD and 17beta-HSD enzymes.
      Histopathology indicated a decreased sperm density in cauda epididymis and
      degeneration of ductus deference. Our study suggested that spearmint probably
      induced oxidative stress in hypothalamus resulting in decreased synthesis of LH
      and FSH which in turn down-regulated the production of testicular testosterone
      through the disruption of a number of intermediate cascades.

PMID- 18804514
TI  - The role of amygdala during auditory verbal imagery of derogatory appraisals by
      others.
AB  - We tend to simulate or recall others' appraisals through auditory verbal imagery
      (AVI) process to react appropriately. In particular, the ability to imagine
      derogatory appraisals by others may be critically important for social survival.
      In this study, we investigated the neural correlates implicated in the processing
      of unpleasant emotion related to derogatory remark and its self-directedness
      during AVI process. Twenty-three right-handed healthy human subjects participated
      in our study. We asked each subject to imagine hearing one's own or another
      person's voice saying derogatory or non-derogatory neutral remarks during the
      scanning of functional magnetic imaging. A test of the interaction between
      derogatory emotion and its self-directedness revealed significant activation of
      the amygdala. Additionally, we observed decreased neural activity in the anterior
      cingulate cortex (ACC) during imagery of derogatory remarks compared to neutral
      remarks. Our findings indicate an important role of the amygdala in the
      processing of unpleasant emotion or self-relevance of information in the real
      world may also be expanded to the processing of self-directedness of unpleasant
      emotion in the imagined world, and thereby contribute to human higher social
      cognitive process. This study also suggests that deactivation of ACC may enable
      us to enact vivid affective responses, and thereby contribute to an effective
      simulation of social interaction.

PMID- 18804515
TI  - Trait cheerfulness modulates BOLD response in lateral cortical but not limbic
      brain areas--a pilot fMRI study.
AB  - Having a good "sense of humor" is an important personality characteristic that
      significantly influences social communication and may represent an important
      coping strategy. To take things "with humor" does not only represent a state
      characteristic but also a personality trait that can reliably be assessed with
      questionnaires like the "state-trait-cheerfulness-inventory" (STCI) by Ruch [Ruch
      et al., Assessing the "humorous temperament": construction of the facet and
      standard trait forms of the state-trait-cheerfulness-inventory-STCI, Humor 9
      (1996) 303-339]. Substantial inter-individual differences among study subjects
      are a key feature of almost all functional magnetic resonance imaging studies on
      higher cognitive functions. Usually, they are considered as "statistical noise"
      and are not recommended for the data analysis, although they can have a high
      intra-individual stability. However, a number of recent fMRI studies found robust
      correlations between inter-individual differences in BOLD response and
      personality traits such as extraversion. The aim of this pilot exploratory study
      was to localise regions where the BOLD response was predicted by "humor
      personality" scores. 10 healthy male subjects viewed funny or non-funny versions
      of Gary Larson cartoons while BOLD response was measured with functional magnetic
      resonance imaging (fMRI). Data were collected from the whole brain (28 slices,
      slice thickness 4 mm, 1 mm gap, TR = 3s). SPM 99 software was used. A simple
      regression analysis with the sub-score cheerfulness from the STCI was applied.
      Higher cheerfulness in the STCI predicted brain activation in the right inferior
      parietal lobule (Tal X, Y, Z: 45, -77, 29), but not in limbic and prefrontal
      brain areas. We conclude that neural correlates of cheerfulness are correlated
      with BOLD response in lateral cortical rather than limbic brain areas. Likely the
      activated region is important for a readiness or tendency to be amused, whereas
      the regions previously shown to be activated in humor appreciation studies are
      related to the understanding of the joke and the emotional reaction.

PMID- 18804516
TI  - Molecular mechanisms of endocrine resistance and their implication in the therapy
      of breast cancer.
AB  - The use of endocrine agents is a safe and effective treatment in the management
      of hormone-sensitive breast cancer. Unfortunately, sooner or later, tumor cells
      develop resistance to endocrine manipulation making useless this approach. During
      the last decade, new molecules and intracellular signaling pathways involved in
      endocrine resistance have been identified. Several studies have documented that
      estrogen receptor signaling may maintain a pivotal role in the tumor growth
      despite the failure of a previous hormonal treatment. In this review we will
      discuss the general principles for optimizing the choice of endocrine therapy
      based on an understanding of the molecular mechanisms responsible for resistance
      to the different anti-hormonal agents.

PMID- 18804517
TI  - Decreased motivational properties of morphine in mouse models of cancerous- or
      inflammatory-chronic pain: implication of supraspinal neuropeptide FF(2)
      receptors.
AB  - Our main purpose was to evaluate the influence of cancer pain on the rewarding
      properties of morphine. Opioids are very addictive when used by healthy persons,
      conversely the occurrence of an opioid addiction seems very low when patients
      suffering from cancer are treated with morphine. We investigated the reinforcing
      properties of morphine in the place preference paradigm on a new model of mice
      suffering from a cancer pain induced by syngenic melanoma cells injected in the
      hind paw. These data were compared with mice suffering either from a short-term-
      or a chronic-inflammatory pain induced respectively by injection of carrageenan
      or complete Freund's adjuvant. Remarkably, mice suffering from cancer pain or
      chronic inflammatory pain did not develop any preference for the environment
      associated with the injection of morphine. In mice injected with melanoma cells,
      the specific binding of [(125)I]EYWSLAAPQRF-NH(2), an agonist of neuropeptide
      FF(2) receptors, was increased in several brain areas involved in the rewarding
      properties of opiates, including the shell of the nucleus accumbens, the major
      islands of Calleja, the ventral endopiriform nucleus and the amygdaloid area. Our
      study is the first to reveal a modification of morphine rewarding properties
      under cancer pain in rodents. We postulate that anti-opioid neuropeptides might
      contribute to the suppression of morphine rewarding effects in this murine model
      of cancer pain.

PMID- 18804518
TI  - Intralaminar nuclei of the thalamus in Lewy body diseases.
AB  - Although the intralaminar thalamus is a target of alpha-synuclein pathology in
      Parkinson's disease, the degree of neuronal loss in Lewy body diseases has not
      been assessed. We have used unbiased stereological techniques to quantify
      neuronal loss in intralaminar thalamic nuclei concentrating alpha-synuclein
      pathology (the anterodorsal, cucullar, parataenial, paraventricular, central
      medial, central lateral and centre-median/parafascicular complex) in different
      clinical forms of Lewy body disease (Parkinson's disease with and without
      dementia, and dementia with Lewy bodies, N=21) compared with controls (N=5).
      Associations were performed in the Lewy body cases between intralaminar cell loss
      and the main diagnostic clinical (parkinsonism, dementia, fluctuation in
      consciousness, and visual hallucinations) and pathological (Braak stage of
      Parkinson's disease) features of these diseases, as well as between cell loss and
      the scaled severity of the alpha-synuclein deposition within the intralaminar
      thalamus. As expected, significant alpha-synuclein accumulation occurred in the
      intralaminar thalamus in the cases with Lewy body disease. Pathology concentrated
      anteriorly and in the central lateral and paraventricular nuclei was related to
      the Braak stage of Parkinson's disease, ageing, and the presence of dementia.
      Across all types of Lewy body cases there was substantial atrophy and neuronal
      loss in the central lateral, cucullar and parataenial nuclei, and neuronal loss
      without atrophy in the centre-median/parafascicular complex. Cases with visual
      hallucinations showed a greater degree of atrophy of the cucullar nucleus,
      possibly due to amygdala denervation. The significant degeneration demonstrated
      in the intralaminar thalamus is likely to contribute to the movement and
      cognitive dysfunction observed in Lewy body disorders.

PMID- 18804519
TI  - Female mini-pig performance of temporal response differentiation, incremental
      repeated acquisition, and progressive ratio operant tasks.
AB  - Increased knowledge of the cognitive abilities of mini-pigs is needed due to
      their increasing use in behavioral neuroscience research. Here, six female
      Yucatan mini-pigs performed tasks thought to measure timing behavior (temporal
      response differentiation, TRD), learning (incremental repeated acquisition, IRA),
      and motivation (progressive ratio, PR). Daily 30-min sessions for food
      reinforcers required a lever press be maintained for at least 10 but no longer
      than 14s (TRD), learning a new sequence of lever presses each test day (IRA) or
      an escalating number of presses for subsequent reinforcers (PR). All animals
      performed PR two days/week while three performed TRD five days/week and the other
      three performed IRA five days/week. Over the four test weeks, no animal completed
      TRD training and only one appeared to progress. For this task, lever press
      maintenance appeared difficult since by choice, the pigs used a front hoof,
      rather than the snout, to press the lever. IRA subjects showed gradually
      increasing performance with response rates comparable to those of rats but below
      those of children and monkeys and accuracy below that for rats. PR response rates
      were higher than those typically reported for rats, but lower than for adult
      rhesus monkeys or children. Physical differences in the way that each species
      responds likely account for these differences.

PMID- 18804520
TI  - Odd-skipped related 1 gene expression is regulated by Runx2 and Ikzf1
      transcription factors.
AB  - Odd-skipped related 1 (Osr1) gene encodes a zinc-finger transcription factor that
      plays important roles in embryonic, heart, and urogenital development, however,
      it is unknown how its expression is regulated. In this study, we analyzed the
      promoter region of Osr1 to elucidate its regulation mechanism. The mouse Osr1
      promoter region was cloned and characterized, and found to have two repressor
      elements in the -4504/-2766 and -1616/-109 regions, and two enhancer elements in
      the -2766/-1616 and -109/+199 regions. Several Runx2 and Ikzf1 binding sites were
      found in both mouse and human Osr1 promoters. Osr1 promoter activity was
      suppressed by cotransfection with Runx2- and Ikzf1-expressing vectors in a dose
      dependent manner. Electrophoresis mobility shift assays showed that purified
      Runx2 bound to proximal (-611/-606) Runx2 binding motifs and that Ikzf1 bound to
      proximal (-1652/-1644) Ikzf1 binding motifs. Chrosmatin immunoprecipitation
      demonstrated that Runx2 bound to both the distal (-3047/-3042) and proximal
      regions, and that Ikzf1 bound to both the far-distal (-3036/-3028) and proximal
      elements. These findings indicate that Osr1 expression is regulated by Runx2 and
      Ikzf1, which are known as master-gene of osteogenesis and hematopoiesis,
      respectively.

PMID- 18804521
TI  - Synthesis and evaluation of dextran-budesonide conjugates as colon specific
      prodrugs for treatment of ulcerative colitis.
AB  - Budesonide is a potent glucocorticoid with high affinity for the glucocorticoid
      receptor, which is now used for the treatment of inflammatory bowel diseases.
      Current oral formulations of budesonide present low efficacy against ulcerative
      colitis because of the premature drug release in the upper part of the
      gastrointestinal tract. The objective of this study was to develop a colon
      specific delivery system for budesonide to increase the efficacy in the treatment
      of ulcerative colitis. Dextran-budesonide conjugates were prepared with different
      molecular weights (MW) of dextran (10,000, 70,000 and 500,000) in the presence of
      dimethylaminopyridine (DMAP) using succinate spacer. The conjugates were
      characterized by (1)H NMR and IR spectroscopy and elemental analysis. The degree
      of substitution, aqueous solubility and chemical stability of conjugates in HCl
      0.1N, phosphate buffer solutions pH 6.8 and 7.4 were studied. Drug release
      characteristics of the conjugates were also studied in the presence of the
      luminal contents of different segments of the rat gastrointestinal tract. Degree
      of substitution (DS) was dependent on the polymer MW and was 19.33, 14.29 and
      11.60 mg/100 mg conjugate for MW 10,000, 70,000 and 500,000, respectively.
      Solubility of the drug in conjugates of MW 10,000 and 70,000 was increased with
      respect to the free drug and was dependent on DS. The three conjugates were found
      to be stable in HCl 0.1N, phosphate buffer solutions pH 6.8 and 7.4 incubated at
      37 degrees C within 6 h and the rate constants for degradation of conjugates to
      budesonide and budesonide hemisuccinate were less than 0.006 h(-1). Less than 10%
      of the drug was released in contents of the stomach and small intestine, while
      about two-fold increase was observed after incubating the conjugates with colonic
      luminal contents. Conjugate prepared by dextran 70,000 showed the most desirable
      solubility, stability and release properties and could therefore be evaluated in
      vivo, for potential clinical use in the treatment of ulcerative colitis.

PMID- 18804522
TI  - Screening of Chinese medicinal plants for inhibition against clinical isolates of
      methicillin-resistant Staphylococcus aureus (MRSA).
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Traditional herbs are a valuable source of novel
      antibacterials in combating pathogenic isolates of methicillin-resistant
      Staphylococcus aureus (MRSA), a global nosocomial problem. AIM OF THE STUDY: To
      assess in vitro anti-MRSA activity of extracts from Chinese herbs. The minimal
      inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs)
      were determined in the setting of clinical MRSA isolates. MATERIALS AND METHODS:
      A collection of 19 plant extracts were obtained and bioassay-guided phytochemical
      analysis performed. Antibacterial susceptibilities were screened for inhibitory
      zone and MICs/MBCs determined by serial dilution with a standardized
      microdilution broth methodology. 9 MRSA isolates and a standard control strain
      (ATCC 25923) were cultured and exposed to the plant extract and isolated
      compound. Vancomycin was used as a positive control agent. RESULTS: All the
      presented 19 plants showed anti-MRSA activity with MIC of 1.25-3.07mg/ml. The
      most active antimicrobial plants were Dendrobenthamia capitata, Elsholtzia
      rugulosa, Elsholtzia blanda, Geranium strictipes and Polygonum multiflorum (MIC<
      or =1.43mg/ml), and betulinic acid isolated from the active ethyl acetate
      fraction of Dendrobenthamia capitata extract was determined with MIC/MBC values
      as 62.5/125.0mg/ml. CONCLUSIONS: Dendrobenthamia capitata, Elsholtzia rugulosa,
      Elsholtzia blanda, Geranium strictipesPolygonum multiflorum and betulinic acid
      demonstrate promising anti-MRSA potential.

PMID- 18804523
TI  - Hoodia gordonii: a natural appetite suppressant.
AB  - AIMS OF THE STUDY: Several species of the stapeliads, a group of stem succulents
      belonging to the family Apocynaceae are reported on in the ethnopharmacology
      literature and many of the references relate to their use as food plants. The
      most important of these plants is Hoodia gordonii, which during the past decade
      has risen from an almost forgotten spiny, desert plant to an important commercial
      appetite-suppressant herbal. The aim of this review is to summarize the botany,
      ethnopharmacology and phytochemistry of Hoodia gordonii. MATERIALS AND METHODS:
      Journal articles and books were used to collect information on Hoodia gordonii
      and related species. RESULTS: Many books and articles documented the use of
      stapeliad species as food plants and earlier references refer to the use Hoodia
      species as a thirst quencher. However, prior to the publication of the patent
      application, only a single reference referring to the use of Hoodia pilifera as
      appetite suppressant was found. The structures of several steroid glycosides
      isolated from Hoodia gordonii are summarized. CONCLUSIONS: Hoodia gordonii
      illustrates how a combination of ethnobotany and scientific research can lead to
      a commercial product which can greatly benefit the indigenous people.

PMID- 18804524
TI  - Ethnobotany in South Africa.

PMID- 18804525
TI  - Studies on the antioxidant effect and interaction of diphenyl diselenide and
      dicholesteroyl diselenide with hepatic delta-aminolevulinic acid dehydratase and
      isoforms of lactate dehydrogenase.
AB  - Studies on the interaction of dicholesteroyl diselenide (DCDS) and diphenyl
      diselenide (DPDS) with hepatic delta-aminolevulinic acid dehydratase (ALA-D) and
      different isoforms of lactate dehydrogenase (LDH) from different tissues were
      investigated. In addition, their antioxidant effects were tested in vitro by
      measuring the ability of the compounds to inhibit the formation of hepatic
      thiobarbituric acid reactive species (TBARS) induced by both iron (II) and sodium
      nitroprusside (SNP). The results show that while DPDS markedly inhibited the
      formation of TBARS induced by both iron (II) and SNP, DCDS did not. Also, the
      activities of hepatic delta-aminolevulinic acid dehydratase (ALA-D) and different
      isoforms of lactate dehydrogenase (LDH) were significantly inhibited by both DPDS
      and DCDS. Moreover, we further observed that the in vitro inhibition of different
      isoforms of lactate dehydrogenase by DCDS and DPDS likely involves the
      modification of the groups at the NAD+ binding site of the enzyme. Since
      organoselenides interacts with thiol groups on proteins, we conclude that the
      inhibition of different isoforms of lactate dehydrogenase by DPDS and DCDS
      possibly involves the modification of the thiol groups at the NAD+ binding site
      of the enzyme.

PMID- 18804526
TI  - Genome-wide identification of osmotic stress response gene in Arabidopsis
      thaliana.
AB  - In this paper, we present a cis-regulatory element based computational approach
      to genome-wide identification of genes putatively responding to various osmotic
      stresses in Arabidopsis thaliana. The rationale of our method is that gene
      expression is largely controlled at the transcriptional level through the
      interactions between transcription factors and cis-regulatory elements. Using cis
      regulatory motifs known to regulate osmotic stress response, we therefore built
      an artificial neural network model to identify other functionally relevant genes
      involved in the same process. We performed Gene Ontology enrichment analysis on
      the 500 top-scoring predictions and found that, except for un-annotated ORFs (
      approximately 40%), 91.3% of the enriched GO classification was related to stress
      response and ABA response. Publicly available gene expression profiling data of
      Arabidopsis under various stresses were used for cross validation. We also
      conducted RT-PCR analysis to experimentally verify selected predictions.
      According to our results, transcript levels of 27 out of 41 top-ranked genes
      (65.8%) altered under various osmotic stress treatments. We believe that a
      similar approach could be extensively adopted elsewhere to infer gene function in
      various cellular processes from different species.

PMID- 18804527
TI  - Molecular signatures associated with transformation and progression to breast
      cancer in the isogenic MCF10 model.
AB  - Comparative microarray analyses provided insight into understanding transcript
      changes during cancer progression; however, a reproducible signature underlying
      breast carcinogenesis has yet to be little available. We utilized gene expression
      profiling to define molecular signatures associated with transformation and
      cancer progression in a series of isogenic human breast cancer cell lines
      including a normal, benign, noninvasive and invasive carcinoma. Clustering
      analysis revealed four distinct expression patterns based on upregulation or
      downregulation patterns. These profiles proved quite useful for describing breast
      cancer tumorigenesis and invasiveness. Downregulation of TNFSF7, S100A4, S100A7,
      S100A8, and S100A9 (calcium-binding protein family), and upregulation of
      kallikrein-5 and thrombospondin-1 were associated with transformation and
      progression of breast cancer cells. Importantly, downregulation of the genes was
      reversed by treatment with silencing inhibitors, implying the potential roles of
      epigenetic inactivation in breast carcinogenesis. Exogenous expressions of S100A8
      and S100A9 inhibit growth in benign and noninvasive carcinoma cells, suggesting
      their negative role in cell proliferation. The data presented here may facilitate
      the identification and functional analyses of prognostic biomarkers for breast
      cancer.

PMID- 18804528
TI  - Co-localization of nitric oxide synthase and choline acetyltransferase in the
      brain of the goldfish (Carassius auratus).
AB  - This work investigates the nitrergic and cholinergic systems in the brain and
      spinal cord of the goldfish (Carassius auratus). We studied the
      immunohistochemical localization of antibodies against the neuronal nitric oxide
      synthase (nNOS) and choline acetyltransferase (ChAT) by bright-field and confocal
      microscopy. Nitrergic and cholinergic cells were segregated within the
      telencephalon, in both dorsal and ventral areas, and co-distributed in some
      nuclei of the diencephalon, mesencephalon, rhombencephalon, and spinal cord.
      Double-labeling experiments revealed nNOS/ChAT-positive cells in (1) the
      diencephalon: the preoptic and suprachiasmatic nuclei, the habenula, the dorsal
      thalamus, and the nucleus of the medial longitudinal fasciculus; (2) the
      mesencephalon: the optic tectum, the mesencephalic portion of the trigeminal
      nucleus, the oculomotor and trochlear nuclei, and the Edinger-Westphal nucleus;
      and (3) the rhombencephalon: the secondary gustatory nucleus, the nucleus isthmi,
      the lateral lemniscus nucleus, the cerebellum, the reticular formation, different
      nuclei of the octaval column, the motor zone of the vagal lobe, and the
      trigeminal, facial, abducens, glosso-pharyngeal, vagal, and hypobranchial motor
      nuclei. Double-labeled cells were also observed in the spinal motor column. The
      percentage of double-labeled cells was different in each studied nucleus,
      indicating a selective distribution pattern. Because double-labeled cells were
      more abundant in those nuclei involved with sensory and motor physiological
      processes, we suggest the involvement of both nitric oxide and acetylcholine in
      these neural functions in fish.

PMID- 18804529
TI  - Olfactory bulb interneurons releasing NO exhibit the Reelin receptor ApoEr2 and
      part of those targeted by NO express Reelin.
AB  - Nitric oxide (NO) and Reelin both modulate neuronal plasticity in developing and
      mature synaptic networks. We recently showed a loss of neuronal nitric oxide
      synthase (nNOS) protein in the olfactory bulb of reeler mutants and advanced the
      hypothesis that the Reelin and NO signalling pathways may influence each other.
      We now studied the distribution of NO sensitive guanylyl cyclase (NOsGC), Reelin
      and its receptor Apolipoprotein E2 (ApoEr2) in the olfactory bulb by multiple
      fluorescence labelling and tested whether nNOS and ApoEr2 colocalize in this
      area. We also essayed the protein content of NOsGC in the reeler olfactory bulb
      and tested whether there are any changes in nNOS and NOsGC protein in other
      reeler brain areas. Olfactory bulb interneurons expressing ApoEr2 and nNOS are
      only few in the glomerular layer but represent the large majority of granule cell
      layer interneurons. Conversely, NOsGC interneurons are rare in the granule cell
      layer and abundant as periglomerular cells. Reelin containing periglomerular
      cells almost entirely belong to the NOsGC subset. These data further support the
      hypothesis of a reciprocal signalling between Reelin/NOsGC and ApoEr2/nNOS
      expressing neurons to affect olfactory bulb activity. We also show that a
      significant rise in NOsGC content accompanies the decrease of nNOS protein in the
      reeler olfactory bulb. The same reciprocal changes present in the cortex/striatum
      and the hippocampus of reeler mice. Thus, the influence that the deficit of
      extracellular Reelin seems to exert on nNOS and its receptor is not limited to
      the olfactory bulb but is a general feature of the reeler brain.

PMID- 18804530
TI  - A novel fluorescent probe for the detection of nitric oxide in vitro and in vivo.
AB  - Fluorescence imaging of nitric oxide (NO) in vitro and in vivo is essential to
      developing our understanding of the role of nitric oxide in biology and medicine.
      Current probes such as diaminofluorescein depend on reactions with oxidized NO
      products, but not with nitric oxide directly, and this limits their
      applicability. Here we report the formation of an imaging probe for nitric oxide
      by coordinating the highly fluorescent chemical 4-methoxy-2-(1H-naphtho[2,3
      d]imidazol-2-yl)phenol (MNIP) with Cu(II). The coordination compound MNIP-Cu
      reacts rapidly and specifically with nitric oxide to generate a product with blue
      fluorescence that can be used in vitro and in vivo. In the present study MNIP-Cu
      was used to reveal nitric oxide produced by inducible nitric oxide synthase in
      lipopolysaccharide (LPS)-activated macrophages (Raw 264.7 cells) and by
      endothelial nitric oxide synthase in endothelial cells (HUVEC). MNIP-Cu was also
      used to evaluate the distribution of nitric oxide synthesis in a model of acute
      liver injury induced by LPS and d-galactosamine in mice. The results demonstrate
      that MNIP-Cu can act as a novel fluorescent probe for nitric oxide and has many
      potential applications in biomedical research.

PMID- 18804531
TI  - Delta-opioid receptors activate ERK/MAP kinase via integrin-stimulated receptor
      tyrosine kinases.
AB  - Integrin-mediated cell adherence to extracellular matrix proteins results in
      stimulation of ERK1/2 activity, a mechanism involving focal adhesion tyrosine
      kinases (pp125FAK, Pyk-2) and epidermal growth factor receptors (EGFRs). G
      protein-coupled receptors (GPCRs) may also mediate ERK1/2 activation in an
      integrin-dependent manner, the underlying signaling mechanism of which still
      remains unclear. Here we demonstrate that the delta-opioid receptor (DOR), a
      typical GPCR, stimulates ERK1/2 activity in HEK293 cells via integrin-mediated
      transactivation of EGFR function. Inhibition of integrin signaling by RGDT
      peptides, cytochalasin, and by keeping the cells in suspension culture both
      blocked [D-Ala(2), D-Leu(5)]enkephalin (DADLE)- and etorphine-stimulated ERK1/2
      activity. Integrin-dependent ERK1/2 activation does not involve FAK/Pyk-2,
      because over-expression of the FAK/Pyk-2 inhibitor SOCS-3 failed to attenuate DOR
      signaling. Exposure of the cells to the EGFR inhibitors AG1478 and BPIQ-I blocked
      DOR-mediated ERK1/2 activation. Because RGDT peptides also prevented DOR-mediated
      EGFR activation, the present findings indicate that in HEK293 cells DOR
      stimulated ERK1/2 activity is mediated by integrin-stimulated EGFRs. Further
      studies with the phospholipase C (PLC) inhibitors U73122 and ET-18-OCH(3)
      revealed that opioid-stimulated integrin activation is sensitive to PLC. In
      contrast, integrin-mediated transactivation of EGFR function appears to be
      dependent on PKC-delta, as indicated by studies with rottlerin and siRNA knock
      down. A similar ERK1/2 signaling pathway was observed for NG108-15 cells, a
      neuronal cell line endogenously expressing the DOR. In these cells, the nerve
      growth factor TrkA receptor replaces the EGFR in connecting DOR-activated
      integrins to the Ras/Raf/ERK1/2 pathway. Together, these data describe an
      alternative ERK1/2 signaling pathway in which the DOR transactivates the growth
      factor receptor associated mitogen-activated protein kinase cascade in an
      integrin-dependent manner.

PMID- 18804532
TI  - Mucoadhesion and drug permeability of free mixed films of pectin and chitosan: an
      in vitro and ex vivo study.
AB  - The objective of this study was to identify the important factors for the drug
      permeability and mucoadhesion of casted free pectin/chitosan combination films.
      The factors varied were: the type of pectin (low and high methoxyl pectin) and
      the ratio pectin:chitosan (25:75, 50:50 and 75:25). The model drug used for
      measuring drug permeability was paracetamol. A texture analyzer was used for
      measuring mucoadhesion by using two different setups: (1) in vitro tensile tests
      measuring the detachment force of films versus a mucin dispersion and (2) ex vivo
      shear tests measuring the friction forces between pre-hydrated films and fresh
      porcine small intestine, with the system immersed in phosphate buffer, pH 6.8.
      The type of pectin used in the combination films did not have a significant
      effect on the drug permeability. The ex vivo mucoadhesion test revealed
      significant differences between low and high methoxyl pectin only for the 50:50
      pectin:chitosan films. For that type of film, the peak and friction forces were
      highest for high methoxyl pectin. Both the mucoadhesion and drug permeability
      generally increased with decreasing amounts of pectin relative to chitosan in the
      films.

PMID- 18804533
TI  - Maintenance immunosuppressive therapy in adult renal transplantation: a single
      center analysis.
AB  - In the present study we have analyzed the maintenance immunosuppression of renal
      transplant patients followed at the Medical University of Vienna. Since more than
      thousand renal transplant patients are registered and treated at this center, our
      data reveal the pattern as well as the current and past practices of the
      prescription of immunosuppressive drugs in a large outpatient setting. The
      majority of patients displayed a transplant vintage of more than 5 years and used
      calcineurin inhibitors (CNIs), and/or steroids and/or antimetabolites reflecting
      the general prescription profile of immunosuppressive drugs in renal transplant
      recipients. However, the selection of immunosuppressive combinations as well as
      the dynamics of the immunosuppressive regimen in the life of the stable allograft
      recipient - minimization, conversion and/or withdrawal of one or more of each of
      the drugs - are not founded on strong data derived from adequately powered
      clinical trials but rather follows a mixture of various smaller and medium-sized
      clinical studies and the individual center attitude based on mostly center
      specific uncontrolled clinical observations. Hence, the maintenance
      immunosuppression of transplant patients is the result of a strong empirical
      attitude and only adequately powered prospective trials may inform us which
      immunosuppressive regimen and overall strategy will be ideal for the individual
      renal transplant recipient.

PMID- 18804534
TI  - Axonal loss and gray matter pathology as a direct result of autoimmunity to
      neurofilaments.
AB  - Axonal damage is considered the major cause of irreversible disability in
      multiple sclerosis (MS). Which mechanisms underlie the damage and whether this is
      secondary to myelin damage remains to be clarified. Recently, we have
      demonstrated that autoimmunity to the axonal/neuronal cytoskeletal protein
      neurofilament light (NF-L) induces axonal damage and neurological disease
      including spasticity - a common feature of MS. To examine the relationship
      between axonal damage and demyelination we have characterized the detailed
      neuropathology of NF-L-induced disease in Biozzi mice compared to classical
      experimental autoimmune encephalomyelitis (EAE) induced with myelin
      oligodendrocyte glycoprotein (MOG). In NF-L-induced neurological disease the
      lesions were predominantly located in the dorsal column displaying extensive
      axonal degeneration, but were also abundant in the gray matter. In contrast,
      lesions in MOG-EAE were restricted to the lateral and ventral columns and
      displayed less axonal damage and little gray matter involvement. The differential
      lesion location was confirmed by quantitation of leukocyte subsets. In both
      diseases myelin damage was a common feature although the numerous empty myelin
      sheaths in NF-L-disease indicative of axonal damage suggest that myelin damage
      was a secondary event. In summary, autoimmunity to NF-L induces a distinct lesion
      topology, axonal damage and gray matter lesions supporting the notion that axonal
      loss and gray matter pathology can be the direct consequence of a primary
      autoimmune attack against axonal antigens such as NF-L rather than merely a
      secondary event to myelin damage.

PMID- 18804535
TI  - Hippocampal transcriptome after status epilepticus in mice rendered seizure
      damage-tolerant by epileptic preconditioning features suppressed calcium and
      neuronal excitability pathways.
AB  - Preconditioning brain with a sub-lethal stressor can temporarily generate a
      damage-refractory state. Microarray analyses have defined the changes in
      hippocampal gene expression that follow brief preconditioning seizures, but not
      the transcriptome after a prolonged and otherwise injurious seizure in previously
      preconditioned brain. Presently, microarray analysis was performed 24 h after
      status epilepticus in mice that had received previously either seizure
      preconditioning (tolerance) or sham-preconditioning (injury). Transcriptional
      changes in the hippocampal CA3 subfield of >or=2 fold were detected for 1357
      genes in the tolerance group compared to a non-seizure control group, with 54% up
      regulated. Of these regulated genes, 792 were also regulated in the injury group.
      Among the remaining 565 genes regulated only in tolerance, 73% were down
      regulated. Analysis of the genes differentially suppressed in tolerance
      identified calcium signaling, ion channels and excitatory neurotransmitter
      receptors, and the synapse as over-represented among pathways, functions and
      compartments. Finally, 12 days continuous EEG recordings determined mice with
      induced tolerance had fewer spontaneous electrographic seizures compared to the
      injury group. Our data suggest the transcriptional phenotype of neuroprotection
      in tolerance may be dictated by the biology of the preconditioning stressor,
      functions by transcriptional reduction of vulnerability to excitotoxicity, and
      has anti-epileptogenic effects.

PMID- 18804536
TI  - Simvastatin inhibits cell cycle progression in glucose-stimulated proliferation
      of aortic vascular smooth muscle cells by up-regulating cyclin dependent kinase
      inhibitors and p53.
AB  - Simvastatin was reported to attenuate platelet-derived growth factor (PDGF)
      induced vascular smooth muscle proliferation by up-regulation of cyclin dependent
      kinase (CDK) inhibitor p27, but had no effect on p16, p21, p53 expression. We
      investigate the mechanisms by which simvastatin inhibits vascular smooth muscle
      cell (VSMC) growth in high glucose conditions to mimic diabetes. Simvastatin was
      added to A7r5 cells cultured in high glucose (25 mM) medium, mimicking diabetes.
      We used an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)
      assay to evaluate cell viability; flow cytometric analysis for cell counts
      distribution in the cell cycle; and Western blot, immunoblotting, and
      immunoprecipitation analyses to evaluate the effects of simvastatin on CDK
      activity and cell cycle regulatory proteins. Cell counts were significantly
      increased in G0/G1 phase and significantly decreased in S and G2/M phases. In our
      study, low dose of simvastatin had no significant inhibitory effect on VSMC
      growth in normal glucose condition. However, both low and high doses of
      simvastatin inhibited VSMC growth significantly in a dose-dependent manner in
      high glucose status. We also found that simvastatin inhibited phosphorylation of
      Rb, promoted expression of p53, p16, p21, p27 and decreased CDK2/4 activity. In
      conclusion, simvastatin inhibits VSMC proliferation in high glucose status,
      mimicking diabetes, inducing a G0/G1 phase cell cycle growth arrest by acting on
      multiple steps upstream of pRb, including inhibition of CDK2/4 expression and up
      regulation of p53, p21, p16, and p27. We propose that statins may be used more
      extensively in diabetic patients regardless of lipid status for preventing
      atherosclerosis and restenosis after PCI.

PMID- 18804537
TI  - An alpha5beta1 integrin inhibitor attenuates glioma growth.
AB  - Integrins are heterodimeric transmembrane proteins, which mediate cell-cell and
      cell-extracellular matrix (ECM) interaction. We show, that an inhibitor of alpha5
      beta1 integrin (alpha5beta1), JSM6427, attenuated glioma growth and decreased the
      density of microglia at the tumor border. 21 days after glioma cell injection
      into an experimental mouse model, the tumor volume was significantly smaller
      after treating animals for 14 days with JSM6427 as compared to controls. We could
      demonstrate the expression of integrin alpha5beta1 on both microglia and glioma
      cells using flow cytometry. In a slice culture we could compare glioma growth in
      the presence and absence of microglia. Slices injected with glioma cells were
      treated with the integrin inhibitor JSM6427 and showed a significant reduction in
      tumor size as compared to control. Depleting microglial cells from the slice
      culture by treatment with clodronate liposomes abrogated the effect of JSM6427 on
      glioma invasion indicating that the presence of microglia is required. We show
      further, that microglial migration, and proliferation was attenuated dose
      dependently by JSM6427.

PMID- 18804538
TI  - The scaffold protein JSAP1 regulates proliferation and differentiation of
      cerebellar granule cell precursors by modulating JNK signaling.
AB  - Cerebellar granule cell precursors (GCPs) proliferate in the outer part of the
      external granular layer (EGL). They begin their differentiation by exiting the
      cell cycle and migrating into the inner part of the EGL. Here we report that
      JSAP1, a scaffold protein for JNK signaling pathways, is expressed predominantly
      in the post-mitotic GCPs of the inner EGL. JSAP1 knockdown or treatment with a
      JNK inhibitor enhances the proliferation of cultured GCPs, but the overexpression
      of wild-type JSAP1 leads to increased proportions of p27(Kip1)- and NeuN-positive
      cells, even with saturating concentrations of Sonic hedgehog (Shh), a potent GCP
      mitogen. However, these differentiation-promoting effects on GCPs are attenuated
      significantly in cells overexpressing a mutant JSAP1 that lacks the JNK-binding
      domain. Together, these data suggest that JSAP1 antagonizes the mitogenic effect
      of Shh on GCPs and promotes their exit from the cell cycle and differentiation,
      by modulating JNK activity.

PMID- 18804539
TI  - Long-term global and regional brain volume changes following severe traumatic
      brain injury: a longitudinal study with clinical correlates.
AB  - Traumatic brain injury (TBI) results in neurodegenerative changes that progress
      for months, perhaps even years post-injury. However, there is little information
      on the spatial distribution and the clinical significance of this late atrophy.
      In 24 patients who had sustained severe TBI we acquired 3D T1-weighted MRIs about
      8 weeks and 12 months post-injury. For comparison, 14 healthy controls with
      similar distribution of age, gender and education were scanned with a similar
      time interval. For each subject, longitudinal atrophy was estimated using SIENA,
      and atrophy occurring before the first scan time point using SIENAX. Regional
      distribution of atrophy was evaluated using tensor-based morphometry (TBM). At
      the first scan time point, brain parenchymal volume was reduced by mean 8.4% in
      patients as compared to controls. During the scan interval, patients exhibited
      continued atrophy with percent brain volume change (%BVC) ranging between -0.6%
      and -9.4% (mean -4.0%). %BVC correlated significantly with injury severity,
      functional status at both scans, and with 1-year outcome. Moreover, %BVC improved
      prediction of long-term functional status over and above what could be predicted
      using functional status at approximately 8 weeks. In patients as compared to
      controls, TBM (permutation test, FDR 0.05) revealed a large coherent cluster of
      significant atrophy in the brain stem and cerebellar peduncles extending
      bilaterally through the thalamus, internal and external capsules, putamen,
      inferior and superior longitudinal fasciculus, corpus callosum and corona
      radiata. This indicates that the long-term atrophy is attributable to
      consequences of traumatic axonal injury. Despite progressive atrophy, remarkable
      clinical improvement occurred in most patients.

PMID- 18804540
TI  - Neural substrates of reward magnitude, probability, and risk during a wheel of
      fortune decision-making task.
AB  - Economic decision-making involves the weighting of magnitude and probability of
      potential gains/losses. While previous work has examined the neural systems
      involved in decision-making, there is a need to understand how the parameters
      associated with decision-making (e.g., magnitude of expected reward, probability
      of expected reward and risk) modulate activation within these neural systems. In
      the current fMRI study, we modified the monetary wheel of fortune (WOF) task
      [Ernst, M., Nelson, E.E., McClure, E.B., Monk, C.S., Munson, S., Eshel, N., et
      al. (2004). Choice selection and reward anticipation: an fMRI study.
      Neuropsychologia 42(12), 1585-1597.] to examine in 25 healthy young adults the
      neural responses to selections of different reward magnitudes, probabilities, or
      risks. Selection of high, relative to low, reward magnitude increased activity in
      insula, amygdala, middle and posterior cingulate cortex, and basal ganglia.
      Selection of low-probability, as opposed to high-probability reward, increased
      activity in anterior cingulate cortex, as did selection of risky, relative to
      safe reward. In summary, decision-making that did not involve conflict, as in the
      magnitude contrast, recruited structures known to support the coding of reward
      values, and those that integrate motivational and perceptual information for
      behavioral responses. In contrast, decision-making under conflict, as in the
      probability and risk contrasts, engaged the dorsal anterior cingulate cortex
      whose role in conflict monitoring is well established. However, decision-making
      under conflict failed to activate the structures that track reward values per se.
      Thus, the presence of conflict in decision-making seemed to significantly alter
      the pattern of neural responses to simple rewards. In addition, this paradigm
      further clarifies the functional specialization of the cingulate cortex in
      processes of decision-making.

PMID- 18804541
TI  - Time-dependent correlation of cerebral blood flow with oxygen metabolism in
      activated human visual cortex as measured by fMRI.
AB  - The aim of this study was to investigate the relationship between relative
      cerebral blood flow (delta CBF) and relative cerebral metabolic rate of oxygen
      (delta CMRO(2)) during continuous visual stimulation (21 min at 8 Hz) with fMRI
      biophysical models by simultaneously measuring of BOLD, CBF and CBV fMRI signals.
      The delta CMRO(2) was determined by both a newly calibrated single-compartment
      model (SCM) and a multi-compartment model (MCM) and was in agreement between
      these two models (P>0.5). The duration-varying delta CBF and delta CMRO(2) showed
      a negative correlation with time (r=-0.97, P<0.001); i.e., delta CBF declines
      while delta CMRO(2) increases during continuous stimulation. This study also
      illustrated that without properly calibrating the critical parameters employed in
      the SCM, an incorrect and even an opposite appearance of the flow-metabolism
      relationship during prolonged visual stimulation (positively linear coupling) can
      result. The time-dependent negative correlation between flow and metabolism
      demonstrated in this fMRI study is consistent with a previous PET observation and
      further supports the view that the increase in CBF is driven by factors other
      than oxygen demand and the energy demands will eventually require increased
      aerobic metabolism as stimulation continues.

PMID- 18804542
TI  - High population connectivity across the Indo-Pacific: Congruent lack of
      phylogeographic structure in three reef fish congeners.
AB  - We used the mitochondrial control region and a comparative approach to study the
      genetic population structure of two surgeonfishes, Naso brevirostris and Naso
      unicornis, across their Indo-central Pacific ranges. Our purpose was to compare
      our results with those of a previous study of Naso vlamingii [Klanten, S.O., van
      Herwerden, L., Choat J.H., 2007. Extreme genetic diversity and temporal rather
      than spatial partitioning in a widely distributed coral reef fish. Mar. Biol.
      150, 659-670] another widely distributed Indo-central Pacific Naso species. We
      found no evidence of a barrier to gene flow between the Indian and Pacific Oceans
      for either species, consistent with what was shown for N. vlamingii. Overall,
      both target species lacked spatial population partitions and probably have
      complex patterns of gene flow on several spatial scales. Despite the lack of
      geographic population structure distinct clades were observed in N. brevirostris,
      similar to those found in N. vlamingii. Coalescence times for intraspecific
      clades of N. brevirostris and N. vlamingii approximate each other, suggesting
      parallel evolutionary histories. A bimodal mismatch distribution in N.
      brevirostris indicates that a biogeographic barrier separated N. brevirostris
      populations sometime during its species history. Naso unicornis, in contrast,
      lacked genetic structure of any kind, although it has what could represent a
      single surviving clade. Congruent lack of spatial population structure among all
      three species suggest that such patterns are not due to stochastic processes of
      DNA mutation and are most likely driven by ecological and environmental factors.

PMID- 18804543
TI  - Mitochondrial DNA reveals the genealogical history of the snake-eyed lizards
      (Ophisops elegans and O. occidentalis) (Sauria: Lacertidae).
AB  - The snake-eyed lizards of the genus Ophisops (Lacertidae) have been through a
      series of taxonomical revisions, but still their phylogenetic relationships
      remain uncertain. In the present study we estimate the phylogeographic structure
      of O. elegans across its distributional range and we evaluate the relationships
      between O. elegans and the sympatric, in North Africa, species O. occidentalis,
      using partial mtDNA sequences (16S rRNA, COI, and cyt b). All phylogenetic
      analyses produced topologically identical trees where extant populations of O.
      elegans and O. occidentalis were found polyphyletic. Taking into account all the
      potential causes of polyphyly (introgressive hybridization, incomplete lineage
      sorting, and imperfect taxonomy) we suggest the inaccurate taxonomy as the most
      likely explanation for the observed pattern. Our results stress the need for re
      evaluation of the current taxonomical status of these species and their
      subspecies. Furthermore, our biogeographic analyses and the estimated time of
      divergences suggest a late Miocene diversification within these species, where
      the present distribution of O. elegans and O. occidentalis was the result of
      several dispersal and vicariant events, which are associated with climatic
      oscillations (the late Miocene aridification of Asia and northern Africa) and
      paleogeographic barriers of late Miocene and Pliocene period.

PMID- 18804544
TI  - A nesting of vipers: Phylogeny and historical biogeography of the Viperidae
      (Squamata: Serpentes).
AB  - Despite their medical interest, the phylogeny of the snake family Viperidae
      remains inadequately understood. Previous studies have generally focused either
      on the pitvipers (Crotalinae) or on the Old World vipers (Viperinae), but there
      has been no comprehensive molecular study of the Viperidae as a whole, leaving
      the affinities of key taxa unresolved. Here, we infer the phylogenetic
      relationships among the extant genera of the Viperidae from the sequences of four
      mitochondrial genes (cytochrome b, NADH subunit 4, 16S and 12S rRNA). The results
      confirm Azemiops as the sister group of the Crotalinae, whereas Causus is nested
      within the Viperinae, and thus not a basal viperid or viperine. Relationships
      among the major clades of Viperinae remain poorly resolved despite increased
      sequence information compared to previous studies. Bayesian molecular dating in
      conjunction with dispersal-vicariance analysis suggests an early Tertiary origin
      in Asia for the crown group Viperidae, and rejects suggestions of a relatively
      recent, early to mid-Tertiary origin of the Caenophidia.

PMID- 18804545
TI  - Parietal cortex, navigation, and the construction of arbitrary reference frames
      for spatial information.
AB  - The registration of spatial information by neurons of the parietal cortex takes
      on many forms. In most experiments, spatially modulated parietal activity
      patterns are found to take as their frame of reference some part of the body such
      as the retina. However, recent findings obtained in single neuron recordings from
      both rat and monkey parietal cortex suggest that the frame of reference utilized
      by parietal cortex may also be abstract or arbitrary in nature. Evidence in rats
      comes from work indicating that parietal activity in freely behaving rodents is
      organized according to the space defined by routes taken through an environment.
      In monkeys, evidence for an object-centered frame of reference has recently been
      presented. The present work reviews single neuron recording experiments in
      parietal cortex of freely behaving rats and considers the potential contribution
      of parietal cortex in solving navigational tasks. It is proposed that parietal
      cortex, in interaction with the hippocampus, plays a critical role in the
      selection of the most appropriate route between two points and, in addition,
      produces a route-based positional signal capable of guiding sensorimotor
      transitions.

PMID- 18804546
TI  - Mapping supramedullary pathways involved in cough using functional brain imaging:
      comparison with pain.
AB  - Several indications suggest that supramedullary brain regions receive sensory
      information from the airways and provide motor control to the brainstem neurons
      that control coughing. However, the organization of this circuitry has not been
      described in any detail. In this short review we will discuss how state-of-the
      art functional brain imaging techniques in humans and animals will enable
      unprecedented insights into the supramedullary brain regions that help control
      coughing. In addition we will describe the likely similarities between cough
      related higher brain networks and those involved in the processing of other
      aversive sensory modalities, such as pain.

PMID- 18804547
TI  - Evidence of caspase-mediated apoptosis induced by l-amino acid oxidase isolated
      from Bothrops atrox snake venom.
AB  - The aim of this work was to investigate the involvement of caspases in apoptosis
      induced by l-amino acid oxidase isolated from Bothrops atrox snake venom. The
      isolation of LAAO involved three chromatographic steps: molecular exclusion on a
      G-75 column; ion exchange column by HPLC and affinity chromatography on a Lentil
      Lectin column. SDS-PAGE was used to confirm the expected high purity level of
      BatroxLAAO. It is a glycoprotein with 12% sugar and an acidic character, as
      confirmed by its amino acid composition, rich in "Asp and Glu" residues. It
      displays high specificity toward hydrophobic l-amino acids. The N-terminal amino
      acid sequence and internal peptide sequences showed close structural homology to
      other snake venom LAAOs. This enzyme induces in vitro platelet aggregation, which
      may be due to H2O2 production by LAAOs, since the addition of catalase completely
      inhibited the aggregation effect. It also showed cytotoxicity towards several
      cancer cell lines: HL60, Jurkat, B16F10 and PC12. The cytotoxicity activity was
      abolished by catalase. A fluorescence microscopy evaluation revealed a
      significant increase in the apoptotic index of these cells after BatroxLAAO
      treatment. This observation was confirmed by phosphatidyl serine exposure and
      activation of caspases. BatroxLAAO is a protein with various biological functions
      that can be involved in envenomation. Further investigations of its function will
      contribute to toxicology advances.

PMID- 18804548
TI  - Regenerative pharmacology in the treatment of genetic diseases: the paradigm of
      muscular dystrophy.
AB  - Current evidence supports the therapeutic potential of pharmacological
      interventions that counter the progression of genetic disorders by promoting
      regeneration of the affected organs or tissues. The rationale behind this concept
      lies on the evidence that targeting key events downstream of the genetic defect
      can compensate, at least partially, the pathological consequence of the related
      disease. In this regard, the beneficial effect exerted on animal models of
      muscular dystrophy by pharmacological strategies that enhance muscle regeneration
      provides an interesting paradigm. In this review, we describe and discuss the
      potential targets of pharmacological strategies that promote regeneration of
      dystrophic muscles and alleviate the consequence of the primary genetic defect.
      Regenerative pharmacology provides an immediate and suitable therapeutic
      opportunity to slow down the decline of muscles in the present generation of
      dystrophic patients, with the perspective to hold them in conditions such that
      they could benefit of future, more definitive, therapies.

PMID- 18804549
TI  - Acetylation of non-histone proteins modulates cellular signalling at multiple
      levels.
AB  - This review focuses on the posttranslational acetylation of non-histone proteins,
      which determines vital regulatory processes. The recruitment of histone
      acetyltransferases and histone deacetylases to the transcriptional machinery is a
      key element in the dynamic regulation of genes controlling cellular proliferation
      and differentiation. A steadily growing number of identified acetylated non
      histone proteins demonstrate that reversible lysine acetylation affects mRNA
      stability, and the localisation, interaction, degradation and function of
      proteins. Interestingly, most non-histone proteins targeted by acetylation are
      relevant for tumourigenesis, cancer cell proliferation and immune functions.
      Therefore inhibitors of histone deacetylases are considered as candidate drugs
      for cancer therapy. Histone deacetylase inhibitors alter histone acetylation and
      chromatin structure, which modulates gene expression, as well as promoting the
      acetylation of non-histone proteins. Here, we summarise the complex effects of
      dynamic alterations in the cellular acetylome on physiologically relevant
      pathways.

PMID- 18804550
TI  - Transcription factors, chromatin and cancer.
AB  - Transcription factors, chromatin and chromatin-modifying enzymes are key
      components in a complex network through which the genome interacts with its
      environment. For many transcription factors, binding motifs are found adjacent to
      the promoter regions of a large proportion of genes, requiring mechanisms that
      confer binding specificity in any given cell type. These include association of
      the factor with other proteins and packaging of DNA, as chromatin, at the binding
      sequence so as to inhibit or facilitate binding. Recent evidence suggests that
      specific post-translational modifications of the histones packaging promoter DNA
      can help guide transcription factors to selected sites. The enzymes that put such
      modifications in place are dependent on metabolic components (e.g. acetyl CoA, S
      adenosyl methionine) and susceptible to inhibition or activation by environmental
      factors. Local patterns of histone modification can be altered or maintained
      through direct interaction between the transcription factor and histone modifying
      enzymes. The functional consequences of transcription factor binding are also
      dependent on protein modifying enzymes, particularly those that alter lysine
      methylation at selected residues. Remarkably, the role of these enzymes is not
      limited to promoter-proximal events, but can be linked to changes in the
      intranuclear location of target genes. In this review we describe results that
      begin to define how transcription factors, chromatin and environmental variables
      interact and how these interactions are subverted in cancer. We focus on the
      nuclear receptor family of transcription factors, where binding of ligands such
      as steroid hormones and dietary derived factors provides an extra level of
      environmental input.

PMID- 18804551
TI  - Nanowire sensors for multiplexed detection of biomolecules.
AB  - Nanowire-based detection strategies provide promising new routes to bioanalysis
      that could one day revolutionize the healthcare industry. This review covers
      recent developments in nanowire sensors for multiplexed detection of biomolecules
      such as nucleic acids and proteins. We focus on encoded nanowire suspension
      arrays and semiconductor nanowire-based field-effect transistors. Nanowire
      assembly and integration with microchip technology is emphasized as a key step
      toward the ultimate goal of multiplexed detection at the point of care using
      portable, low power, electronic biosensor chips.

PMID- 18804552
TI  - Role of H2AX in DNA damage response and human cancers.
AB  - H2AX, the evolutionarily conserved variant of histone H2A, has been identified as
      one of the key histones to undergo various post-translational modifications in
      response to DNA double-strand breaks (DSBs). By virtue of these modifications,
      that include acetylation, phosphorylation and ubiquitination, H2AX marks the
      damaged DNA double helix, facilitating local recruitment and retention of DNA
      repair and chromatin remodeling factors to restore genomic integrity. These
      modifications are essential for effective DSB repair, so is their removal for
      cell, to recover from checkpoint arrest. Because of these vital roles during DSB
      signaling and also its activation during early cancer stages, H2AX is emerging as
      an intriguing gene in tumor biology, supported further by frequent deletion of
      the region harboring this gene. This review focuses on the insights gained from
      recent studies on dynamic regulation of H2AX in DSB repair. Also, posing future
      challenges in the area of chromatin reorganization and retention of epigenetic
      signature post-DSB-repair with implication of its haploinsufficiency in human
      cancers.

PMID- 18804553
TI  - Forty-six genes causing nonsyndromic hearing impairment: which ones should be
      analyzed in DNA diagnostics?
AB  - Hearing impairment is the most common sensory disorder, present in 1 of every 500
      newborns. With 46 genes implicated in nonsyndromic hearing loss, it is also an
      extremely heterogeneous trait. Here, we categorize for the first time all
      mutations reported in nonsyndromic deafness genes, both worldwide and more
      specifically in Caucasians. The most frequent genes implicated in autosomal
      recessive nonsyndromic hearing loss are GJB2, which is responsible for more than
      half of cases, followed by SLC26A4, MYO15A, OTOF, CDH23 and TMC1. None of the
      genes associated with autosomal dominant nonsyndromic hearing loss accounts for a
      preponderance of cases, although mutations are somewhat more frequently reported
      in WFS1, KCNQ4, COCH and GJB2. Only a minority of these genes is currently
      included in genetic diagnostics, the selection criteria typically reflecting: (1)
      high frequency as a cause of deafness (i.e. GJB2); (2) association with another
      recognisable feature (i.e. SLC26A4 and enlarged vestibular aqueduct); or (3) a
      recognisable audioprofile (i.e. WFS1). New and powerful DNA sequencing
      technologies have been developed over the past few years, but have not yet found
      their way into DNA diagnostics. Implementing these technologies is likely to
      happen within the next 5 years, and will cause a breakthrough in terms of power
      and cost efficiency. It will become possible to analyze most - if not all -
      deafness genes, as opposed to one or a few genes currently. This ability will
      greatly improve DNA diagnostics, provide epidemiological data on gene-based
      mutation frequencies, and reveal novel genotype-phenotype correlations.

PMID- 18804554
TI  - Silkworm as a model animal to evaluate drug candidate toxicity and metabolism.
AB  - To evaluate the feasibility of using the silkworm as a model animal for screening
      drug candidates, we examined whether the lethal dose of cytotoxic chemicals in
      silkworm, Bombyx mori, were consistent with those in mammals, and compared the
      metabolic pathways of these drugs between silkworms and mice. The lethal dose
      levels of cytotoxic chemicals in silkworms were consistent with those in mammals.
      We examined the fate of model drugs, 4-methyl umbelliferone, umbelliferone, and 7
      ethoxycoumarine, in silkworm larvae. The half-life of 4-methyl umbelliferone in
      the silkworm larvae hemolymph was 7.0+/-0.1 min, similar to that in mouse blood.
      In silkworm larvae, 4-methyl umbelliferone was conjugated with glucose, whereas
      in mammals it is conjugated with glucuronate or sulfate. These results are
      consistent with a previous report that UDP-glucosyltransferase catalyzes the
      conjugation of 4-methyl umbelliferone. The glucose-conjugation reaction of 4
      methyl umbelliferone was observed in microsomal fractions of fat bodies isolated
      from silkworms. Furthermore, most umbelliferone and 7-ethoxycoumarine injected
      into the hemolymph of silkworms was eliminated through the feces in the glucose
      conjugated form. These findings suggest that chemicals are metabolized through a
      pathway common to both mammals and silkworms: reaction with cytochrome P450,
      conjugation with hydroxylated compounds, and excretion.

PMID- 18804557
TI  - Granulocyte/monocyte apheresis as immunotherapic tool: cellular adsorption and
      immune modulation.
AB  - Cellular apheresis is now established as a rational therapeutic procedure in
      certain inflammatory and autoimmune diseases, particularly in inflammatory bowel
      diseases, but the efficacy of this procedure can not be fully explained solely on
      the basis of removal of granulocytes and monocytes. It is suggested that a
      selective modulator increase of regulatory T cells contributes to beneficial
      effect of adsorptive leukocytapheresis in patients with these pathologies. Though
      currently applied as second-line medication, it could be considered in the future
      as an effective alternative to the use of immune suppressive regimens or
      biological agents and taken into account to establish a tailor's patient therapy
      in inflammatory and autoimmune conditions.

PMID- 18804558
TI  - Cloning, bacterial expression, and unique structure of adenosylhomocysteine
      hydrolase-like protein 1, or inositol 1,4,5-triphosphate receptor-binding protein
      from mouse kidney.
AB  - Adenosylhomocysteine hydrolase (SAHase)-like protein 1 (SAH-L), also called
      inositol 1,4,5-triphosphate receptor-binding protein (IRBIT) is a novel protein
      involved in fish embryo development and calcium release in mammalian cells
      through protein-protein interactions. To better understand its reaction
      mechanism, purified protein is indispensable. Here we describe a simple
      purification procedure and the unique properties of SAH-L. The cDNA was isolated
      from mouse kidney by RT-PCR and inserted into various pETtrade mark vectors.
      Escherichia coli harboring a plasmid coding for SAH-L with a C-terminal His-tag
      could solely produce a soluble protein. SAH-L purified through a Ni(2+) column
      gave M(r)s of 59,000 and 190,000 by SDS-PAGE and gel filtration, respectively,
      which is suggestive of a trimer, but chemical cross-linking experiments
      demonstrated a dimer. The incompatible M(r) values implicate an irregular
      structure of SAH-L. In fact, SAH-L was partially purified in a form lacking the
      31 N-terminal residues, and was found to be extremely susceptible to proteases in
      the region around residue 70. The N-terminal polypeptide (residues 1-98) was also
      expressed as a soluble form and was trypsin-sensitive. Circular dichroism
      revealed a low alpha-helix content but not a randomly extended structure.
      Interestingly, SAH-L contained tightly bound NAD(+) despite showing no SAHase
      activity. The characterized properties of SAH-L and its N-terminal fragment
      present the notion that the structure of the protease-sensitive N-terminal region
      is relatively loose and flexible rather than compact, and which protrudes from
      the major SAHase-like domain. This structure is supposed to be favorable to
      interact with the IP(3) receptor.

PMID- 18804556
TI  - An automated communication system in a contact registry for persons with rare
      diseases: scalable tools for identifying and recruiting clinical research
      participants.
AB  - OBJECTIVES: Strategies for study recruitment are useful in clinical research
      network settings. We describe a registry of individuals who have self-identified
      with one of a multiplicity of rare diseases, and who express a willingness to be
      contacted regarding possible enrollment in clinical research studies. We evaluate
      this registry and supporting tools in terms of registry enrollment and impact on
      participation rates in advertised clinical research studies. METHODS: A web-based
      automated system generates periodic and customized communications to notify
      registrants of relevant studies in the NIH Rare Diseases Clinical Research
      Network (RDCRN). The majority of these communications are sent by email. We
      compare the characteristics of those enrolled in the registry to the
      characteristics of participants enrolled in sampled RDCRN studies in order to
      estimate the impact of the registry on study participation in the network.
      RESULTS: The registry currently contains over 4000 registrants, representing 40
      rare diseases. Estimates of study participation range from 6-27% for all
      enrollees. Study participation rates for some disease areas are over 40% when
      considering only contact registry enrollees who live within 100 mi of a clinical
      research study site. CONCLUSIONS: Automated notifications can facilitate
      consistent, customized, and timely communication of relevant protocol information
      to potential research subjects. Our registry and supporting communication tools
      demonstrate a significant positive impact on study participation rates in our
      network. The use of the internet and automated notifications make the system
      scalable to support many protocols and registrants.

PMID- 18804555
TI  - Pioglitazone versus vitamin E versus placebo for the treatment of non-diabetic
      patients with non-alcoholic steatohepatitis: PIVENS trial design.
AB  - BACKGROUND: Non-alcoholic steatohepatitis (NASH) is a common liver disease
      associated with obesity and diabetes. NASH is a progressive disorder that can
      lead to cirrhosis and liver failure. Insulin resistance and oxidative stress are
      thought to play important roles in its pathogenesis. There is no definitive
      treatment for NASH. OBJECTIVES: PIVENS is conducted to test the hypotheses that
      treatment with pioglitazone, a thiazolidinedione insulin sensitizer, or vitamin
      E, a naturally available antioxidant, will lead to improvement in hepatic
      histology in non-diabetic adults with biopsy proven NASH. DESIGN: PIVENS is a
      randomized, multicenter, double-masked, placebo-controlled trial to evaluate
      whether 96 weeks of treatment with pioglitazone or vitamin E improves hepatic
      histology in non-diabetic adults with NASH compared to treatment with placebo.
      Before and post-treatment liver biopsies are read centrally in a masked fashion
      for an assessment of steatohepatitis and a NAFLD Activity Score (NAS) consisting
      of steatosis, lobular inflammation, and hepatocyte ballooning. The primary
      outcome measure is defined as either an improvement in NAS by 2 or more in at
      least two NAS features, or a post-treatment NAS of 3 or less, and improvement in
      hepatocyte ballooning by 1 or more, and no worsening of fibrosis. METHODS: PIVENS
      enrollment started in January 2005 and ended in January 2007 with 247 patients
      randomized to receive either pioglitazone (30 mg q.d.), vitamin E (800 IU q.d.),
      or placebo for 96 weeks. Participants will be followed for an additional 24 weeks
      after stopping the treatment. The study protocol incorporates the use of several
      validated questionnaires and specimen banking. This protocol was approved by all
      participating center Institutional Review Boards (IRBs) and an independent Data
      and Safety Monitoring Board (DSMB) which was established for monitoring the
      accumulated interim data as the trial progresses to ensure patient safety and to
      review efficacy as well as the quality of data collection and overall study
      management. (ClinicalTrials.gov number, NCT00063622).

PMID- 18804559
TI  - Proteasomal ATPases are associated with rDNA: the ubiquitin proteasome system
      plays a direct role in RNA polymerase I transcription.
AB  - Significant amount of data have accumulated in the last several years pointing to
      the essential role of the ubiquitin proteasome system in the regulation of RNA
      polymerase II transcription; however, its involvement in RNA polymerase I
      transcription has remained largely unexplored. In this study, we demonstrate that
      proteasome activity is required for pre-rRNA synthesis. We can detect the
      association of proteasomal ATPases with both the rDNA promoter and coding region.
      Additionally, we show that the RNA polymerase I associated transcription factor,
      TIF-IA interacts with proteasomal ATPases, representing a potential link via
      which proteasomes and/or proteasome related complexes are recruited to rRNA
      genes. In summary, our findings suggest that the ubiquitin proteasome system is
      directly involved in RNA polymerase I transcription in analogy to the RNA
      polymerase II system.

PMID- 18804560
TI  - Are topical NSAIDs needed for routine cataract surgery?

PMID- 18804561
TI  - Interferon-gamma release assays in the diagnosis of tuberculous uveitis.

PMID- 18804562
TI  - Clinical features of cytomegalovirus anterior uveitis in immunocompetent
      patients.

PMID- 18804564
TI  - Time-domain and spectral-domain optical coherence tomography in uveitic macular
      edema.

PMID- 18804567
TI  - Intraocular pressure after cataract extraction and contractility of ciliary
      muscle.

PMID- 18804568
TI  - [Abstracts of the 25th Congress of the SFE (French Society of Endocrinology),
      October 2008, Lille, France].

PMID- 18804569
TI  - An update on recent advances in bone regeneration.
AB  - SUMMARY: Bone loss from trauma, neoplasia, reconstructive surgery and congenital
      defects remains a major health problem, making the development of effective bone
      regeneration therapies a primary priority. The long-term clinical goal is to
      reconstruct bony tissue in an anatomically functional three-dimensional
      morphology. Today, the science of bone regeneration is in its infancy with
      current and emerging therapies still having significant limitations. In addition
      to bone grafting, current bone regeneration strategies include the application of
      different bioactive factors, cell types, biologic or artificial scaffolds, alone
      or in various combinations. Recently, efforts are focused more on understanding
      the normal bone regenerative process where multiple factors interact in a defined
      temporal and spatial cascade of events. Bone biology has benefited over the last
      decade from an explosion of information regarding the molecular mechanisms
      underlying bone formation and resorption, as well as the feedback signals
      controlling these complex homeostatic mechanisms. New insights in the complexity
      of the homeostatic mechanisms regulating bone remodeling have uncovered potential
      therapeutic strategies for bone repair.

PMID- 18804570
TI  - Biological considerations of mesenchymal stem cells and endothelial progenitor
      cells.
AB  - SUMMARY: Mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs)
      have been demonstrated as an attractive cell source for tissue engineering
      applications because of their ability to be isolated and expanded. Even though
      MSCs and EPCs constitute a powerful candidate cell type for regenerative
      medicine, more knowledge in terms of their biological properties is required
      before using these cells as a routinely applied therapy in the clinical setting.
      The nature of their mobilizing, migratory and homing signals and the mechanisms
      of differentiation and incorporation into the target tissues need to be clarified
      and further characterized. This paper examines the biological properties of these
      cells, the animal trials that have been performed so far and highlights their
      therapeutic potential in the treatment of musculoskeletal and cardiovascular
      diseases.

PMID- 18804571
TI  - Allograft and bone morphogenetic proteins: an overview.
AB  - SUMMARY: Allograft is frequently used in orthopaedic and trauma surgery. On top
      of safety issues its biological activity is limited also due to processing.
      Consequently, the combination of allograft with osteoinductive substances may
      increase its effectiveness and decrease failure rates. In particular Bone
      Morphogenetic Proteins (BMPs) seem to be a promising partner for clinical
      applications. This overview focuses on the combined application of
      allograft/BMPs. Current points of view from available literature are summarized.

PMID- 18804572
TI  - Carrier systems and application of growth factors in orthopaedics.
AB  - SUMMARY: With optimal surgical treatment within an appropriate time frame, bony
      tissue has the potential to regenerate defects without the formation of scar
      tissue. However, even under optimal mechanical circumstances and appropriate
      operative treatment, healing can fail and delayed or non-union occur. In Europe
      delayed bone healing leads to socio-economic costs of up to 14.7 billion euros
      per year. In addition to the optimal clinical treatment, the success of bone
      regeneration depends on the following main aspects: (1) adequate mechanical
      stabilization and biological competence of the organism, (2) osteogenic cells,
      (3) osteoconductive structures or scaffolds, and (4) growth factors (Diamond
      Concept)(1). Further, (5) a sufficient vascularisation is essential for the
      nutritive supply. Within the last years two growth factors, BMP-2 and BMP-7, were
      approved for clinical use in orthopaedic and trauma surgery for different
      indications.(2,3) The establishment of carrier systems and application techniques
      for growths factors is the focus of current research. The combination of a well
      established stabilization system and local drug delivery system for bioactive
      factors could be a therapeutical strategy to optimize bone healing and reduce the
      complication rate, in the future.

PMID- 18804573
TI  - Fracture vascularity and bone healing: a systematic review of the role of VEGF.
AB  - SUMMARY: Fracture healing constitutes a complex and delicate physiological
      process. Local vascularity at the site of the fracture has been identified as one
      of the most significant parameters influencing the healing procedure. VEGF is the
      most important component of the regeneration of the vascular system at the
      fracture site. The aim of this review is to determine the evidence supporting the
      direct role of VEGF in the enhancement of fracture healing and the possible
      clinical use of VEGF for non-unions. The literature search was performed via the
      internet using the Medline. The key words which were searched in the abstracts
      were the terms "VEGF", "angiogenesis", "fracture", "bone" and "healing". Twenty
      five articles were relevant to the topic of interest. A total of 11 articles were
      excluded from our research due to non conformity of their content to the
      inclusion criteria. Evidence retrieved suggests that VEGF could be extremely
      valuable for the treatment of critical size bone defects and that VEGF could have
      a direct effect on osteoprogenitor cells, mainly by promoting the differentiation
      of osteoblasts and by increasing the mineralisation of the regenerated bone. The
      former observation could have very interesting repercussions for the field of non
      unions and the latter for the field of osteoporosis.

PMID- 18804574
TI  - The diamond concept--open questions.
AB  - SUMMARY: In the Trauma and Orthopaedic discipline, tissue engineering attempts to
      convert scientific knowledge into new products and methods of treatment in order
      to advance the repair, replacement, or regeneration of tissues such as bone,
      cartilage, tendon and ligament. Currently, tissue engineering strategies are
      based mainly on cell and tissue-based approaches. We have previously reported
      that the standard tissue engineering approach to provide solutions for impaired
      fracture healing, bone restoration and regeneration must include the utilisation
      of growth factors, scaffolds, mesenchymal stem cells and an optimal mechanical
      environment (diamond concept). These strategies are already benefiting patients,
      but as our understanding of the physiological processes increases, a number of
      questions come up requiring clarification and answers. In this article, important
      issues which continue to remain obscured are discussed.

PMID- 18804575
TI  - Classification of non-union: need for a new scoring system?
AB  - SUMMARY: A new scoring system is proposed in order to assist surgeons with the
      complex analysis associated with non-union surgery. Patients with non-union are
      rarely easily compared with one another and this has frustrated research in this
      field. We have therefore attributed values to clinical features based on clinical
      experience and research evidence, so that patients of similar complexity can be
      compared with one another. When greater experience with this scoring system has
      been gained it will be further refined and validated. We propose that surgeons
      with a sub specialist interest in non-union surgery use this system in reporting
      results, and that non- specialist surgeons use it to inform their decision to
      treat the fracture themselves, or refer to a sub specialist.

PMID- 18804576
TI  - OP-1 application in bone allograft integration: preliminary results in sheep
      experimental surgery.
AB  - Massive bone allografts are frequently used in orthopaedic reconstructive
      surgery. However the failure rate at long term follow-up is around 25%. AIM:
      Stimulation of allograft incorporation. MATERIALS AND METHODS: In order to
      stimulate bone remodeling of an allograft we applied recombinant human osteogenic
      protein-1 (rh-OP-1, also know as bone morphogenetic protein-7, BMP-7) to a long
      bone critical size defect sheep model. In nine sheep we created a 3 cm
      osteoperiosteal metatarsal defect replaced with a structural allograft alone
      (control group, 4 animals), or an allograft added with rh-BMP-7 (BMP group, 5
      animals). Radiographic, mechanical, histological and histomorphometric analysis
      were performed. RESULTS: X-rays in the BMP group showed a better and faster
      callus formation, compared to the control group within the first 8 weeks after
      surgery. After 16 weeks there was a higher evidence of bone remodeling in the BMP
      group. Radiographic healing at junction sites was more evident in the BMP group
      at 4, 8 and 16 weeks. Mechanical testing on screw extraction showed no
      statistical differences between the two groups and histomorphometry showed no
      difference in terms of newly formed bone inside the allograft as well. The
      resorption rate of the graft was higher in the BMP group in comparison to the
      control group. The penetration of newly formed vessels was significantly higher
      in the BMP group. CONCLUSIONS: These findings indicate that BMP-7 added to a
      structural bone allograft inducing early remodeling of the graft through
      stimulation of neo-angiogenesis and osteoclastic activity, without negative
      effects in mechanical strength and clinical outcome.

PMID- 18804577
TI  - A comparison of RhBMP-7 (OP-1) and autogenous graft for metaphyseal defects after
      osteotomy of the distal radius.
AB  - SUMMARY AIM: The aim of the study was to demonstrate whether RhBMP-7 is an
      effective alternative to autogenous bone graft in the healing of metaphyseal
      defects in the distal radius following corrective osteotomies for symptomatic
      malunion after distal radial fractures. PATIENTS AND METHODS: Thirty patients
      were entered into the study and were randomised to receive either RhBMP-7 or
      autogenous bone graft harvested from the ipsilateral iliac crest. Stabilisation
      of the osteotomy was either carried out with non- bridging external fixation or
      the pi-plate. Clinical, radiographic and functional review were carried out at
      regular intervals up to 1 year. RESULTS: The first 10 patients were treated using
      non-bridging external fixation of the osteotomy. Two of the 4 patients treated
      with RhBMP-7 developed excessive osteolysis around the osteotomy site resulting
      in loss of the corrected position and non-union of the osteotomy. The other 2
      patients healed at 13 weeks. The 6 patients treated with autogenous bone graft
      all healed at an average of 7 weeks, without any complications. It was postulated
      that the osteolysis was related to instability of the osteotomy site, and the use
      of external fixation was abandoned and replaced with internal fixation with a
      dorsal pi-plate. In the pi-plate group of patients, 10 were treated with
      autogenous bone graft and 10 with RhBMP-7. The bone graft patients healed at 7
      weeks compared to 18 weeks for the RhBMP-7 patients, which was statistically
      significant (p = 0.019). The patients who received bone graft had complete
      filling of the metaphyseal defect radiologically. Five patients treated with
      RhBMP-7 healed at the volar cortex with a dorsal defect remaining at 1 year. Two
      patients developed non-union radiologically. Ten patients (3 in the RhBMP-7 and 7
      in the bone graft groups) required plate removal for soft tissue complications.
      CONCLUSION: RhBMP-7 does not confer the same stability as bone graft, allowing
      shear forces across the osteotomy site when used in conjunction with non-bridging
      external fixation, reducing the capacity for healing and resulting in osteolysis.
      Using the RhBMP-7 with a pi-plate resulted in healing of the osteotomy, but at a
      slower rate than autogenous bone graft.

PMID- 18804578
TI  - Application of BMP-7 to tibial non-unions: a 3-year multicenter experience.
AB  - SUMMARY: The effective treatment of the often debilitating, longlasting and large
      asset-consuming complication of fracture non-unions has been in the centre of
      scientific interest the last decades. The use of alternative bone substitutes to
      the gold standard of autologous graft includes the osteoinductive molecules named
      bone morphogenetic proteins (BMPs). A multicenter registry and database
      (bmpusergroup.co.uk) focused on the application of BMP-7/OP-1 was created in
      December 2005. We present the preliminary results, using the prospective case
      series of aseptic tibial non-unions as an example. Sixty-eight patients fulfilled
      the inclusion criteria for this observational study, with a minimum follow-up of
      12 months. The median duration of tibial non-union prior to BMP-7 application was
      23 months (range 9-317 mo). Patients had undergone a median of 2 (range 0-11)
      revision procedures prior to the administration of BMP-7. In 41% the application
      of BMP-7 was combined with revision of the fixation at the non-union site. Non
      union healing was verified in 61 (89.7%) in a median period of 6.5 months (range
      3-15 mo). No adverse events or complications were associated with BMP-7
      application. The safety and efficacy of BMP-7 was verified in our case series,
      and was comparable to the existing evidence. The establishment of multicenter
      networks and the systematic and long-term follow- up of these patients are
      expected to provide further information and significantly improve our
      understanding of this promising osteoinductive bone substitute.

PMID- 18804579
TI  - Tissue engineering for bone defect healing: an update on a multi-component
      approach.
AB  - SUMMARY: The need for an interdisciplinary approach in order to establish new
      therapeutic strategies for the therapy of bone defects has been acknowledged by
      the scientific community for many years. This awareness makes itself felt when
      looking at the multitude of approaches--ranging from cell-based to scaffold-based
      strategies and also including the use of osteogenic growth factors and genetic
      engineering--that are currently being combined to assess their potential to
      develop effective concepts for the treatment of extensive loss of osseous tissue.
      With a strong focus on the preclinical research in this field, the goal of this
      review is to give an update on the multi-component approaches that are currently
      being investigated in tissue engineering of bone.

PMID- 18804580
TI  - The use of flaps to reconstruct soft-tissue defects plays an important role in
      the management of soft tissue injuries.

PMID- 18804581
TI  - Soft-tissue injury in orthopaedic trauma.
AB  - SUMMARY: This paper reviews the current concepts of soft-tissue injury in
      orthopaedic trauma. Six topics are described in this Injury Supplement, including
      influencing factors and mechanisms, co-morbidities, biological responses,
      diagnosis and treatment of closed soft-tissue injury, compartment syndrome and
      gunshot wounds. Since one of the current AO principles emphasises respect for
      soft tissue when performing open reduction and internal fixation, this article
      further discusses the pathophysiology of soft-tissue injury and the specific
      concerns in treating compartment syndrome and gunshot injury. Understanding the
      basic and updated principles of soft-tissue management will be beneficial for the
      clinical practice of orthopaedic trauma surgeons.

PMID- 18804582
TI  - Factors affecting the success of arterialised venous flaps in the hand.
AB  - SUMMARY: Arterialised venous flaps provide skin with thin subcutaneous tissue,
      making them suitable for covering skin defects on the hand. However, they are
      often susceptible to subsequent unpredictable superficial or partial necrosis. We
      performed a retrospective analysis of the free arterialised venous flaps that we
      had used in patients to identify prognostic factors that correlate with flap
      necrosis. 51 flaps in 51 patients met the following criteria and were subjected
      to statistical analysis. They had an elliptical shape and were harvested from the
      medial aspect of the ipsilateral forearm to cover skin deficits distal to the
      wrist joint. Each flap contained one axial flow-through subcutaneous vein, the
      vein stumps of which were approximated to a recipient artery and a recipient
      vein. The patient's age at the time of surgery, the recipient site of the flap
      and the size of the flap were examined in each case. Multivariate analysis showed
      that the size of the flap was the factor that correlated statistically with a
      successful result after a flap operation. Arterialised venous flaps in which the
      product of the lengths of the long and short axes (mm) was less than 767 were
      less likely to develop necrosis of the skin.

PMID- 18804583
TI  - Reconstruction of a phalangeal bone using a vascularised metacarpal bone graft
      nourished by a dorsal metacarpal artery.
AB  - SUMMARY: We report on a patient with an infected nonunion of the left little
      finger phalanges following a gunshot injury. The defect was treated by
      transplanting a partial fifth metacarpus, vascularised by the fourth dorsal
      metacarpal vessels. Bone union was obtained 6 months after surgery and no signs
      of infection were found at the site of the nonunion. Although the range of the
      interphalangeal joints of the finger was limited, the patient was satisfied
      because the preserved little finger had a metacarpophalangeal (MP) joint with
      unrestricted motion.

PMID- 18804584
TI  - Artificial nerve tubes and their application for repair of peripheral nerve
      injury: an update of current concepts.
AB  - SUMMARY: Over the last 20 years, an increasing number of research articles have
      reported on the use of artificial nerve tubes to repair nerve defects. The
      development of an artificial nerve tube as an alternative to autogenous nerve
      grafting is currently a focus of interest for peripheral nerve repair. The
      clinical employment of tubes as an alternative to autogenous nerve grafts is
      mainly justified by the limited availability of donor tissue for nerve autografts
      and the related morbidity. Numerous studies indicate that short-distance defects
      in humans can be successfully treated by implantation of artificial nerve guides.
      This review provides a brief overview of various preclinical and clinical trials
      conducted to evaluate the utility of artificial nerve tubes for the regeneration
      of peripheral nerves. This review is also intended to help update hand surgeons
      on the rapid advances in tubulization techniques, and to provide them with
      indications of the various directions toward which future research can proceed.
      Future studies need to provide us with as much comparative information as
      possible on the effectiveness of different tubulization techniques, in order to
      guide the surgeon in choosing the best indications for their optimal clinical
      employment. Future progress in implant development can be expected from
      interdisciplinary approaches involving both materials and life sciences, leading
      to advances in neuro-tissue engineering that will be needed to effectively treat
      larger nerve defects.

PMID- 18804585
TI  - Measurement of tibial endothelial cell function after cigarette smoking,
      cessation of smoking and hyperbaric oxygen therapy.
AB  - SUMMARY: Cigarette smoking is hazardous to a range of human tissues. For
      instance, cigarette smoke inhalation has been proven to delay bone healing. This
      study analysed the effects of cigarette smoking on tibial vascular endothelium
      and blood flow using the bone-chamber model. The effects of smoking cessation and
      hyperbaric oxygen (HBO) on the damage caused by smoking were also compared. 54
      adult New Zealand rabbits were divided into three groups. Group 1: control, Group
      2: 1 week smoking, and Group 3: 6 weeks' smoking. This study on rabbits confirmed
      that both short-term and long-term cigarette smoking is dangerous to the bony
      vascular endothelium of the tibia. The vasodilatation caused by nitric oxide
      production was significantly attenuated in Group 2 and 3's tibia. Long-term
      smoking damaged the vascular endothelium more severely than short-term smoking
      (P<.01). Cessation of smoking effectively reduces the adverse effects of smoking
      when the cessation time equals the smoking time. HBO also effectively reduces the
      adverse effects of smoking.

PMID- 18804586
TI  - Flow-through anterolateral thigh flap for simultaneous soft tissue and long
      vascular gap reconstruction in extremity injuries: anatomical study and case
      report.
AB  - SUMMARY: 47 dissections of cadaver thigh were studied to investigate pedicle
      configurations in the lateral descending branch of the lateral circumflex femoral
      arterial system, which can be used in harvesting a flow-through anterolateral
      thigh flap. The descending branch arose from the lateral circumflex femoral
      artery in 38 of the dissections, and the mean diameter at its origin was 3.0mm
      (range, 2.2-4.0mm). Skin peforators were of the solely musculocutaneous type in
      37 dissections and were a combined septo-musculocutaneous type in 10 dissections.
      Pure septocutaneous perforator was not found in this study. During the descending
      branch's journey to the distal part of the thigh, several branches went into the
      vastus lateralis and vastus intermedius muscles. The diameters were tapering and
      the mean terminal diameter was 1.3mm (range 0.9-1.8mm), which required
      intraoperative judgment for proper matching of diameter of the flow-through
      pedicle and the recipient artery. The mean total length of the descending branch
      from its origin to terminus was 30.3 cm (range 22.5-37.1cm). In four dissections,
      the descending branch could not be used as a flow-through anterolateral thigh
      flap because the origin of the perforator arose from the transverse branch. A
      flow-through anterolateral thigh flap has several advantages, including a large
      cutaneous area, acceptable donor-site morbidity, adjustable thickness, the
      ability to combine adjacent muscle or fascia lata and the possibility of
      simultaneous reconstruction of long arterial gap and soft-tissue defects. Four
      patients with severe injury and a vascular gap of longer than 10 cm in the
      extremities were used to confirm the usefulness of this application.

PMID- 18804587
TI  - Reconstruction of limb soft-tissue defects: using pedicle perforator flaps with
      preservation of major vessels, a report of 45 cases.
AB  - SUMMARY: We report on 45 pedicle perforator flaps without harvesting major
      vessels in limb reconstruction. Of our patients, 25 had major vessel injury
      resulting from their initial injury. In the upper extremities, there were 13
      posterior interosseous artery perforator flaps, four ulnar artery perforator
      flaps and three radial artery perforator flaps. In the lower extremities, there
      were 16 peroneal artery perforator flaps with an axis on the sural nerve, five
      peroneal artery perforator flaps with an axis on the superficial peroneal nerve
      and four posterior tibial artery perforator flaps with an axis on the saphenous
      nerve. There were 42 successes, one total flap loss, one epidermal necrolysis and
      one distal tip necrosis. Greater utilisation of pedicle perforator flaps probably
      will occur because they are technically simple to execute, violate only the
      involved extremity, do not sacrifice a major source vessel, bring similar local
      tissues into a defect, avoid prolonged immobilisation and do not require
      microsurgical expertise. The concept of the pedicle perforator flap can be
      applied to the same axis of a neurocutaneous flap, even in cases with injured
      cutaneous nerves.

PMID- 18804588
TI  - Reconstruction of upper extremity large soft-tissue defects using pedicled
      latissimus dorsi muscle flaps--technique illustration and clinical outcomes.
AB  - SUMMARY: Reconstruction of large soft-tissue defects of an upper extremity is
      very challenging due to the unavailability of expendable local muscle.
      Appropriate soft-tissue restoration is an essential component of such
      reconstruction treatment protocols, and often requires a vascularised flap to
      protect the exposed neurovascular and musculotendinous structures. The latissimus
      dorsi muscle makes an ideal pedicled flap because of its long neurovascular
      pedicle, large size, ease of mobilisation and expendability. Moreover, the flap
      provides well-vascularised tissue from a region far from the area of injury. This
      paper describes the technique for pedicle latissimus dorsi flap transfer and also
      reports the authors' experience of its application for the acute treatment of
      massive upper-extremity soft-tissue injuries. 20 patients with large soft-tissue
      defects over the upper extremity caused by trauma and infection underwent
      aggressive debridements and immediate soft-tissue reconstruction using a pedicled
      latissimus dorsi muscle flap. Successful reconstructions were achieved and
      primary healing of wounds occurred in all patients, with minor complications. The
      donor site morbidity was minimal. At a mean of 3.6 years' follow-up (range: 1.5-6
      years), all functional results were good and the patients were satisfied with
      their outcomes.

PMID- 18804589
TI  - Soft-tissue injury management and flap reconstruction for mangled lower
      extremities.
AB  - SUMMARY: The treatment for mangled lower extremities poses a clinical challenge
      for orthopaedic surgeons. The complexities of soft-tissue injury combined with
      open fractures and osteomyelitis have frequently resulted in amputation of the
      lower extremity. The current advances in soft-tissue flap reconstruction
      techniques have significantly improved the results of limb-salvage attempts.
      Understanding the reconstructive ladders around the zone of injury, debridement,
      timing and nuances of techniques regarding skin graft, local and distant flaps
      and microsurgical reconstruction is necessary to complete limb salvage in a
      timely and appropriate fashion. Various soft-tissue flap applications have been
      described, including emergent flow-through flap, acute soft-tissue flap, acute
      combined soft-tissue and bone flap, pedicle gastrocnemius/soleus flap, pedicle
      sural artery flap, soft-tissue flap for chronic osteomyelitis, composite osseous
      myocutaneous flap for chronic osteomyelitis and free functioning muscle flap for
      functional reconstruction of mangled lower limbs. Clinical experience of 850
      flaps reconstructions for mangled lower limbs in both acute and chronic stages
      has revealed that adequate application of flap technique was able to achieve
      quite acceptable results. This article provides a comprehensive review of the
      soft-tissue injury management and flap reconstruction for mangled lower limbs.

PMID- 18804590
TI  - Treatment for scaphoid fracture and nonunion--the application of 3.0 mm
      cannulated screws and pedicle vascularised bone grafts.
AB  - SUMMARY BACKGROUND: Scaphoid fractures are very common in wrist trauma, and
      scaphoid nonunions with avascular necrosis are frequent complications of a
      fractured scaphoid. The purpose of these two retrospective studies was to examine
      the clinical and x-ray results of treatments for acute scaphoid fracture and
      scaphoid nonunion. The surgical techniques of cannulated screw fixation and
      pedicled vascularised bone graft are described. METHODS: From 2001-2004, 80
      patients with scaphoid fractures were treated with 3.0 mm cannulated screws and
      5.5 mm threaded washers in our hospitals. The average age was 35 years, and the
      average time from injury to surgery was 16.5 hours. Outcomes were assessed by x
      ray and the modified Mayo wrist score system. During the 6-year period of 1998
      2004, 72 patients with scaphoid nonunions were treated using pedicled
      vascularised bone graft (VBG)in our hospitals. The average age was 38.5 years,
      and the average time from injury to surgery was 9.5 months. RESULTS: The union
      rate was 96.25% and satisfactory function rate was 93.75% in acute scaphoid
      fractures with an average follow-up of 3.5 years. The union rate (90.28%) and
      satisfactory function rate (81.94%) achieved in scaphoid nonunions were
      acceptable, with an average follow-up of 5 years. CONCLUSIONS: Our studies
      suggested that appropriate application of a cannulated screw and threaded washer
      was able to produce satisfactory results in scaphoid fracture, and that pedicled
      vascularised bone graft was effective for treating scaphoid nonunion.

PMID- 18804591
TI  - Recent development of interaction of transition metal complexes with DNA based on
      biosensor and its applications.
AB  - In this article interaction of transition metal complexes with DNA and its
      applications in electrochemical DNA biosensors as hybridization indicator or
      electroactive marker of DNA are reviewed. Special emphasis has been given to the
      efforts for the development of new transition metal complexes and their
      interaction to DNA. DNA and polymers covalently conjugated with transition metal
      complexes were also reviewed.

PMID- 18804592
TI  - Advances in technologies for the measurement of uranium in diverse matrices.
AB  - An overview of the advances in technologies, which can be used in the field as
      well as in a laboratory for the measurement of uranium in diverse matrices like,
      waters, minerals, mineralized rocks, and other beneficiation products for its
      exploration and processing industries is presented. Laser based technologies, ion
      chromatography, microsample X-ray analysis method followed by energy dispersive X
      ray fluorescence technique (MXA-EDXRF), sensors for electrochemical detection
      followed by cyclic voltammogram and alpha liquid scintillation counting
      techniques are the most promising techniques. Among these techniques, laser
      fluorimetry/spectrofluorimetry, in particular, is the technique of choice because
      of its high performance qualification (PQ), inherent sensitivity, simplicity,
      cost effectiveness, minimum generation of analytical waste, rapidity, easy
      calibration and operation. It also fulfills the basic essential requirements of
      reliability, applicability and practicability (RAPs) for the analysis of uranium
      in solution of diverse matrices in entire nuclear fuel cycle. A very extensive
      range of uranium concentrations may be covered. Laser fluorimetry is suitable for
      direct determination of uranium in natural water systems within the microg L(-1)
      and mg L(-1) range while differential technique in laser fluorimetry (DT-LIF) is
      suitable for mineralized rocks and concentrates independent of matrix effects
      (uranium in samples containing >0.01% uranium). The most interesting feature of
      TRLIF is its capability of performing speciation of complexes directly in
      solution as well as remote determination via fiber optics and optrode. Future
      trend and advances in lasers, miniaturization and automation via flow injection
      analysis (FIA) has been discussed.

PMID- 18804593
TI  - Determination of Hg and organomercury species following SPME: a review.
AB  - Mercury is ubiquitous in the environment and exists in a variety of chemical and
      physical forms as a result of both natural and man-made releases. Mercury, and
      specially, its organic species are toxic being the subject of much concern.
      Consequently, significant effort has been made to develop methods for its
      determination in environmental and biological samples. The state of the art of
      the analytical procedures based on solid-phase microextraction (SPME) and its
      applications to mercury and organomercury determination in abiotic and biotic
      matrixes are critically reviewed. Firstly, sample pretreatment prior to SPME is
      evaluated including a description of the most usual leaching procedures for
      sediment, soil and biological samples. Excluding the volatile organometallics
      that can be directly extracted from the sample by SPME, usually, those species
      lack of volatility and then a derivatization step is mandatory prior to gas
      chromatographic (GC) determination. The most common derivatization procedures
      used for mercury will be highlighted. The variables usually evaluated along the
      methodology to improve the sensitivity of the SPME, such as sampling size,
      stirring procedures and sampling temperature, polymer coating and thermal
      desorption have been reviewed.

PMID- 18804594
TI  - Stability-indicating determination of meropenem in presence of its degradation
      product.
AB  - Stability-indicative determination of meropenem (MERM) in the presence of its
      open-ring degradation product, the metabolite, is investigated. The degradation
      product has been isolated, via acid-degradation, characterized and confirmed.
      Selective quantification of MERM, singly in bulk form, pharmaceutical
      formulations and/or in the presence of its major degradate is demonstrated. The
      indication of stability has been undertaken under conditions likely to be
      expected at normal storage. Among the analytical techniques adopted for
      quantification are spectrophotometry [first-derivative ((1)D), first-derivative
      of ratio spectra ((1)DD) and bivariate analysis], as well as chromatography
      [coupled TLC-densitometry and HPLC].

PMID- 18804595
TI  - Electrocatalytic activity of horseradish peroxidase/chitosan/carbon microsphere
      microbiocomposites to hydrogen peroxide.
AB  - Colloidal carbon microspheres (CMS) are dispersed in chitosan (CHIT) solution to
      form an organic-inorganic hybrid with excellent micro-environment for the
      immobilization of biomolecules. A novel amperometric biosensor for the
      determination of hydrogen peroxide (H(2)O(2)) has been constructed by entrapping
      horseradish peroxidase (HRP) in as-synthesized CMS/CHIT hybrid. The modification
      of glassy carbon electrode is made by a simple solution-evaporation method. The
      electrochemical properties of the biosensor are characterized in electrochemical
      methods. The proposed biosensor shows high sensitive determination and fast
      response to H(2)O(2) at -0.15 V. The constructed HRP/CHIT/CMS/GC electrode also
      exhibits a fine linear correlation with H(2)O(2) concentration. The calculated
      value of the apparent Michaelis-Menten constant, 2.33 mM, suggests that the HRP
      in CMS/CHIT hybrid keeps its native bioactivity and has high affinity for
      H(2)O(2).

PMID- 18804596
TI  - Development of a photosystem II-based optical microfluidic sensor for herbicide
      detection.
AB  - Herbicides are highly toxic for both human and animal health. The increased
      application of herbicides in agriculture during the last decades has resulted in
      the contamination of both soil and water. Herbicides, under illumination, can
      inhibit photosystem II electron transfer. Photosynthetic membranes isolated from
      higher plants and photosynthetic micro-organisms, immobilized and stabilized, can
      serve as a biorecognition element for a biosensor. The inhibition of photosystem
      II causes a reduced photoinduced production of hydrogen peroxide, which can be
      measured by a chemiluminescence reaction with luminol and the enzyme horseradish
      peroxidase. In the present work, a compact and portable sensing device that
      combines the production and detection of hydrogen peroxide in a single flow assay
      is proposed for herbicide detection.

PMID- 18804597
TI  - Application of the Bahe's pseudolattice theory to water-1-butyl-3
      methylimidazolium tetrafluoroborate (bmimBF4) mixtures at 298.15K: Part II.
      Acidity scales.
AB  - Molten salts at room temperature and their mixtures with water or molecular
      solvents are excellent candidates for future replacement of most of organic
      solvents used in many industrial processes. To make this possible and to allow
      efficient application, it is necessary to determine physico-chemical parameters
      (such as the acidity scales) for these reaction media. This work follows a study
      of the autoprotolysis constants (K(s)) of water-1-butyl-3-methylimidazolium
      tetrafluoroborate (bmimBF(4)) mixtures at 298.15K over the composition range of 0
      77.43 vol.% bmimBF(4) [I. Bou Malham, P. Letellier, M. Turmine, Talanta 72 (2007)
      155-164]. In this second analysis, we determined the values of the dissociation
      constant (pK(a)) of various conjugate acid-base pairs for the same water
      bmimBF(4) mixtures, to establish acidity scales for each medium. These data can
      be used to produce proton buffer solutions and thus to control the acidity level
      of water-ionic liquid (IL) mixtures. We compare the values of pK(a) for acid-base
      pairs in water-bmimBF(4) mixtures with published values for water-methanol
      mixtures.

PMID- 18804598
TI  - Mercury speciation in sea food by flow injection cold vapor atomic absorption
      spectrometry using selective solid phase extraction.
AB  - An on-line inorganic and organomercury species separation, preconcentration and
      determination system consisting of cold vapor atomic absorption spectrometry (CV
      AAS or CV-ETAAS) coupled to a flow injection (FI) method was studied. The
      inorganic mercury species was retained on a column (i.d., 3 mm; length 3 cm)
      packed to a height of 0.7 cm with a chelating resin aminopropyl-controlled pore
      glass (550 A) functionalized with [1,5-bis (2 pyridyl)-3-sulphophenyl methylene
      thiocarbonohydrazyde] placed in the injection valve of a simple flow manifold.
      Methylmercury is not directly determined. Previous oxidation of the
      organomercurial species permitted the determination of total mercury. The
      separation of mercury species was obtained by the selective retention of
      inorganic mercury on the chelating resin. The difference between total and
      inorganic mercury determined the organomercury content in the sample. The
      inorganic mercury was removed on-line from the microcolumn with 6% (m/v)
      thiourea. The mercury cold vapor generation was performed on-line with 0.2% (m/v)
      sodium tethrahydroborate and 0.05% (m/v) sodium hydroxide as reducing solution.
      The determination was performed using CV-AAS and CV-ETAAS, both approaches have
      been used and compared for the speciation of mercury in sea food. A detection
      limit of 10 and 6 ng l(-1) was achieved for CV-AAS and CV-ETAAS, respectively.
      The precision for 10 replicate determinations at the 1 microg l(-1) Hg level was
      3.5% relative standard deviation (R.S.D.), calculated from the peak heights
      obtained. Both approaches were validated with the use of two certified reference
      materials and by spiking experiments. By analyzing the two biological certified
      materials, it was evident that the difference between the total mercury and
      inorganic mercury corresponds to methylmercury. The concentrations obtained by
      both techniques were in agreement with the certified values or with differences
      of the certified values for total Hg(2+) and CH(3)Hg(+), according to the t-test
      for a 95% confidence level. It is amazing how this very simple method is able to
      provide very important information on mercury speciation.

PMID- 18804599
TI  - On-line and off-line quantification of trace elements associated to colloids by
      As-Fl-FFF and ICP-MS.
AB  - A quantification procedure of trace elements during colloid size fractionation
      was developed and validated. This procedure is based on the hyphenation between
      Asymmetrical Flow Field-Flow Fractionation (As-Fl-FFF) and Inductively Coupled
      Plasma Mass Spectrometer (ICP-MS). The optimisation of the procedure was
      performed on a soil leachate spiked with six trace elements selected for their
      environmental and health impact (As, Cd, Sb, Se, Sn and Pb). The elements in the
      spiked sample were on-line monitored during the fractionation. The validation was
      carried out by comparison with a second off-line quantification procedure based
      on fraction collection and total element analysis by ICP-MS. This off-line one
      was previously validated using reference materials. Finally, the analytical
      performances of the two procedures were compared.

PMID- 18804600
TI  - Fluorescence sensors for trace monitoring of dissolved ammonia.
AB  - Even though monitoring of dissolved ammonia is acutely important for
      environmental studies, fish farms and for industrial surveillance, no system for
      the performance of online measurements at the concentrations needed exists so
      far. For many applications it is necessary to detect dissolved ammonia
      concentrations at sub mg/l-levels, because ammonia is reported to be toxic for
      aquatic organisms above 25 microg/l. We present new ammonia sensitive materials
      consisting of fluorescent pH indicators embedded into different cellulose esters.
      The low pK(a) value of the indicators and the high solubility of ammonia in the
      cellulose polymers lead to detection limits below 1 microg/l and a dynamic range
      between 5 and 1000 microg/l. Response times at these trace concentration levels
      are in the order of 20-30 min. The sensors are suitable for fresh and sea water
      monitoring by an additional silicon layer preventing the interference of protons
      and salinity. The fluorescent indicators Eosin ethylester and 2',7'
      dichlorofluorescein methylester (DCF) were investigated to achieve sensors with a
      dynamic range matching the target concentrations. Sensors with improved
      performance were obtained by employing cellulose ester nanospheres with
      incorporated Eosin ethylester. The simple sensor design has a high potential to
      be applied in miniaturized optical measurement system for online ammonia
      detection.

PMID- 18804601
TI  - Pre-concentration procedure for determination of copper and zinc in food samples
      by sequential multi-element flame atomic absorption spectrometry.
AB  - In this paper is proposed a simultaneous pre-concentration procedure using cloud
      point extraction for the determination of copper and zinc in food samples
      employing sequential multi-element flame atomic absorption spectrometry (FS
      FAAS). The reagent used is 1-(2-pyridylazo)-2-naphthol (PAN) and the micellar
      phase is obtained using the non-ionic surfactant octylphenoxypolyethoxyethanol
      (Triton X-114) and centrifugation. The optimization step was performed using Box
      Behnken design for three factors: solution pH, reagent concentration and buffer
      concentration. A multiple response function was established in order to get an
      experimental condition for simultaneous extraction of copper and zinc. Under the
      optimized experimental conditions, the method allows the determination of copper
      with a limit of detection (3sigma(b)/S, LOD) of 0.1 microg L(-1), precision
      expressed as relative standard deviation (R.S.D.) of 2.1 and 1.3% (N=10), for
      copper concentrations of 10 and 50 microg L(-1), respectively. Zinc is determined
      with a LOD of 0.15 microg L(-1) and precision as R.S.D. of 2.7 and 1.7% for
      concentrations of 10 and 50 microg L(-1), respectively. The enhancement factors
      obtained were 36 and 32 for copper and zinc, respectively. The accuracy was
      assessed by analysis of certified reference materials, namely, SRM 1567a - Wheat
      Flour and SRM 8433 - Corn Bran from National Institute of Standards & Technology
      and BCR 189-wholemeal flour from Institute of Reference Materials and
      Measurements. The method was applied to the determination of copper and zinc in
      oats, powdered chocolate, corn flour and wheat flour samples. The copper content
      in the samples analyzed varied from 1.14 to 3.28 microg g(-1) and zinc from 8.7
      to 22.9 microg g(-1).

PMID- 18804602
TI  - Development of an electronic nose to identify and quantify volatile hazardous
      compounds.
AB  - A new electronic nose was developed to identify the chemical compound released
      when a 2.5-L flask was broken inside a 3 m x 3 m x 2.5 m store-room. Flasks of 10
      different hazardous compounds were initially present in the room: ammonia,
      propanone, hexane, acetic acid, toluene, methanol, tetrachloromethane,
      chloroform, ethanol and dichloromethane. Besides identification, quantification
      of the compound present in the air was also performed by the electronic nose, in
      order to evaluate the risk level for room cleaning. An array of six sensors based
      on coated piezoelectric quartz crystals was used. Although none of the individual
      sensors was specific for a single compound, an artificial neural network made it
      possible to identify and quantify the released vapour, among a series of 10
      compounds, with six sensors. The neural network could be simplified, and the
      number of neurons reduced, provided it was used just for the identification task.
      Quantification could be performed later using the individual calibration of the
      sensor most sensitive to the identified compound.

PMID- 18804603
TI  - Modeling the adsorption of dyes onto activated carbon by using experimental
      designs.
AB  - We used experimental design methodologies to obtain the response surface of the
      adsorption process for three acid dyes used in the dyeing step of a tanning
      process. The dyes were Acid Red 97, Acid Orange 61 and Acid Brown 425. The
      adsorption process was evaluated determining the concentrations of individual and
      total dyes remaining in solution at the end of the process. These concentrations
      were determined simultaneously in a single step using sequential injection
      analysis with multivariate curve resolution alternating least squares (SIA-MCR
      ALS). This method involves fractional factorial designs and the steepest ascent
      method to find a zone of efficient adsorption and a response surface-modeling
      step to fit the relevant adsorption factors for the response.

PMID- 18804604
TI  - Hydroxyl radical detection with a salicylate probe using modified CUPRAC
      spectrophotometry and HPLC.
AB  - Reactive oxygen species (ROS) may attack biological macromolecules giving rise to
      oxidative stress-originated diseases, so it is important to establish efficient
      methods to screen hydroxyl radical scavengers for antioxidant therapy. Since *OH
      is very short-lived, secondary products resulting from *OH attack to various
      probes are measured. As a low-cost measurement technique, we used a salicylate
      probe for detecting hydroxyl radicals generated from an equivalent mixture of
      Fe(II)+EDTA with hydrogen peroxide. The produced hydroxyl radicals attacked both
      the probe and the water-soluble antioxidants in 37 degrees C-incubated solutions
      for 2 h. The CUPRAC (cupric ion reducing antioxidant capacity) assay absorbance
      of the ethylacetate extract due to the reduction of Cu(II)-neocuproine reagent by
      the hydroxylated probe decreased in the presence of *OH scavengers, the
      difference being proportional to the scavenging ability of the tested compound.
      Attack by *OH radicals upon salicylate produced 2,3-dihydroxybenzoate, 2,4
      dihydroxybenzoate, and 2,5-dihydroxybenzoate as major products. HPLC separation
      combined with CUPRAC spectrophotometry was used to identify and quantify
      hydroxylated salicylate derivatives in the presence of synthetic water-soluble
      antioxidants and green tea infusion. The developed spectrophotometric method for
      *OH detection was validated with HPLC, i.e., the concentrations of
      dihydroxybenzoates produced by radical attack from the probe were determined by
      HPLC, and the sum of (concentrationxabsorptivity) products of these components
      approximately agreed with the experimentally found CUPRAC absorbances, confirming
      the validity of Beer's law for the selected system. Statistical comparison of the
      results found with the proposed methodology and HPLC was made with two-way ANOVA
      (analysis of variance) test. Under optimal conditions, about 53% of the probe
      (salicylate) was converted into dihydroxybenzoate isomers in the absence of *OH
      scavengers, and these isomers were more specific markers of hydroxyl radicals
      than the non-specific malondialdehyde end-product of the TBARS test. Thus, the
      more costly and less speedy HPLC method could advantageously be substituted with
      the proposed spectrophotometric assay of *OH detection, which was also of much
      higher yield than the TBARS colorimetric assay.

PMID- 18804605
TI  - Comparison of two stationary phases for the separation of five selected
      polyphenols.
AB  - In this study, a conventional TEKNOKROMA, Tr-015605 TRACER EXTRASIL ODS2 (25 cm x
      0.4 cm, i.d. 5 microm) column and a new stationary phase TEKNOKROMA, Tr-010065
      Mediterranea sea(18) (15 cm x 0.4 cm, i.d. 3 microm) were compared for the
      separation of five phenolic compounds. Sensitivity, performance characteristics,
      analysis time and method validation were reported for both columns. A better
      sensitivity and performance were achieved with the novel chromatographic support.
      In addition the total analysis time was significantly reduced. The method was
      applied to the determination of the selected polyphenols in commercial available
      white wines. LC-MS was used as a confirmatory technique.

PMID- 18804606
TI  - Development of an optical fibre reflectance sensor for p-aminophenol detection
      based on immobilised bis-8-hydroxyquinoline.
AB  - 2,2'-(1,4-Phenylenedivinylene)bis-8-hydroxyquinoline (PBHQ), a highly sensitive
      reagent used for the colorimetric determination of p-aminophenol (PAP), was
      successfully immobilised on XAD-7 and coupled with optical fibres to investigate
      a sensor-based approach for determining p-aminophenol. The solid-state sensor is
      based on the reaction of PAP with PBHQ in presence of an oxidant to produce an
      indophenol dye. The reflectance measurements were carried out at a wavelength of
      647 nm since it yielded the largest divergence different in reflectance spectra
      before and after reaction with the analyte. The linear dynamic range of PAP was
      found within the concentration range of 0.1-2.18 mg l(-1) with its LOD of 0.02 mg
      l(-1). The sensor response from different probes (n=7) gave a R.S.D. of 4.4% at
      1.09 mg l(-1) PAP concentration. The response time of the optical one-shot sensor
      was 5 min for a stable solution. As this PAP sensor is irreversible, a fresh
      sensor has to be used for each measurement. All the experimental parameters were
      optimized for the determination of PAP. Using the optical sensing probe, PAP in
      pharmaceutical wastewater and paracetamol was determined. The effect of potential
      interferences such as inorganic and organic compounds was also evaluated.
      Potential on-site determination of PAP with such sensors can indirectly aid
      detection of organo-phosphorus nerve agents and pesticides in the field by
      inhibition of acetylcholine esterase-catalyzed hydrolysis of p-aminophenyl
      acetate to p-aminophenol.

PMID- 18804607
TI  - The use of headspace solid phase microextraction for the characterization of
      volatile compounds in olive oil matrices.
AB  - Two different fibre coatings, for solid phase microextraction (SPME) sampling,
      poly(dimethylsiloxane) (PDMS) and poly(acrylate) (PA), were studied in order to
      test, for olive oil matrixes, two mathematical models that relate the directly
      proportional relationship between the amount of analyte absorbed by a SPME fibre
      and its initial concentration in the sample matrices. Although the PA fibre was
      able to absorb higher amounts of compounds from the olive oil sample, the
      equilibrium was reached later then with the PDMS fibre. In both cases, the amount
      of analyte present affected the time profile or the equilibrium time in two of
      the concentrations studied, 0.256 microL/kg, 2.56 microL/kg and for 2-ethylfuran,
      pentan-3-one, pent-1-en-3-one, hexanal, trans,trans-non-2,4-dienal and in the
      four concentrations studied, 0.256 microL/kg, 2.56 microL/kg, 6.25 microL/kg and
      400 microL/kg, for 4-methyl-pent-3-en-2-one, 2-methylbutan-1-ol, methoxybenzene,
      hexan-1-ol, cis-hex-3-en-1-ol, trans-hex-2-en-1-ol, 2-ethyl-hexan-1-ol and
      trans,trans-dec-2,4-dienal. Comparing the mathematical models of both fibres, the
      PA-coated fibre showed direct proportionality between the initial concentration
      and amount extracted, that allows the possibility of relative quantification in a
      non-equilibrium state in non-aqueous media. The same was not observed for the
      PDMS fibre.

PMID- 18804608
TI  - Dedicated mother wavelet in the determination of antimony in the presence of
      copper.
AB  - In this paper, a new signal-processing procedure is applied to the optimization
      of voltammetric determination of antimony in the presence of copper and the
      parallel determination of these two elements. The proposed numerical algorithm
      for the separation of the overlapping peaks utilizes the continuous wavelet
      transform and the inverse continuous wavelet transform. As the base function, the
      specially defined dedicated mother wavelet is used. In its construction the
      ideal, simulated voltammetric peak is intensively exploited. This approach,
      corresponding to the wavelet theory, gives satisfactory signals separation, even
      in the cases when they constitute one peak. The possibility of Sb(III)
      determination is presented in the case of different distances between copper and
      antimony peaks and also in 10-, 20- and 50-fold excesses of Cu. The parallel
      determination of Cu(II) and Sb(III) is possible even in the case of a 10-fold
      excess of copper. The quality of the obtained results fulfills the requirements
      of validation.

PMID- 18804609
TI  - Time-resolved fluoroimmunoassay for quantitative determination of ampicillin in
      cow milk samples with different fat contents.
AB  - In this paper, we have reported an immunoassay with time-resolved revelation
      system for ampicillin in raw milk samples. Immunological methods appear to be a
      promising approach in the analysis of beta-lactam compounds, because they do not
      need previous sample pre-treatments. In fact, beta-lactam ring is not very stable
      in extensive sample pre-treatment procedures requested in conventional analytical
      techniques. Specimens were collected from lactating cows bred in various
      conditions and assayed for the fat contents. Ampicillin was assayed in samples
      with different fat concentrations. The assay was performed using ampicillin
      specific polyclonal antibody raised in rabbit; the immunogen was synthesized
      using bovine thyroglobulin conjugated to ampicillin by glutaraldehyde reaction;
      as fluorescent marker we used goat anti-rabbit IgG conjugated with a chelating
      molecule complexed with Eu(3+). Bovine serum albumin (BSA) conjugated with
      ampicillin was synthesized and used to prepare a solid phase on polystyrene
      microtiter plates. The use of a lanthanide chelate as label allowed to achieve 1
      ng mL(-1) sensitivity, which is four times more sensitive than limits requested
      from European Community. Fat contents did not affect the assay performance.

PMID- 18804610
TI  - Simultaneous determination of cefotaxime and desacetylcefotaxime in real urine
      sample using voltammetric and high-performance liquid chromatographic methods.
AB  - Two rapid, accurate and sensitive methods are developed and validated for the
      quantitative simultaneous determination of cefotaxime (CFX) and its active
      metabolite desacetylcefotaxime (DCFX) in urine. Based on the previous results
      which showed the four electron reduction of CFX at approximately -0.5 V, and the
      new findings that DCFX reduction occurred at more positive potential (-0.23 V),
      the new adsorptive stripping differential pulse voltammetric (AdSDPV) method was
      developed for determination of CFX in the presence of DCFX. Linear responses were
      observed over a wide concentration range (0.07-0.52 microg/ml for CFX and 0.22
      1.3 microg/ml for DCFX) in urine. The second assay involves subsequent separation
      on a reversed-phase HPLC column, with ultraviolet detection at 262 nm. Retention
      times were 4.057 and 1.960 min for CFX and DCFX, respectively. Linear responses
      were observed over a wide range, 0.55-6.60 microg/ml for CFX and 1.10-11.00
      microg/ml for DCFX, in urine. The statistical evaluation for both methods was
      examined by means of within-day repeatability (n=5) and day-to-day precision
      (n=3) and was found to be satisfactory with high accuracy and precision.

PMID- 18804611
TI  - Enzyme-linked immunosorbent assay (ELISA) based on superparamagnetic
      nanoparticles for aflatoxin M1 detection.
AB  - Five different clones of antibodies developed against the aflatoxin M(1) were
      investigated by using the classical indirect and direct competitive Enzyme-Linked
      Immunosorbent Assay (ELISA) formats, and also the direct competitive ELISA based
      on the use of the superparamagnetic nanoparticles. The purpose of this study was
      to assess if not so friendly time classical ELISA procedures can be further
      improved, by reducing the coating, blocking and competition time. Here we showed
      that a complete dc-ELISA (coating, blocking and competition step) based on the
      use of superparamagnetic nanoparticles can be performed in basically 40 min, if
      coating step (20 min) should be taken into account. Moreover, the standard
      analytical characteristics of the proposed method fulfil the requirements for
      detecting AFM(1) in milk, in a wide linear working range (4-250 ng/L). The IC(50)
      value is 15 ng/L. The matrix effect and the recovery rate were assessed, using
      the European Reference Material (BD282, zero level of AFM(1)), showing an
      excellent percentage of recovery, close to 100%.

PMID- 18804612
TI  - Multivariate near infrared spectroscopy models for predicting the iodine value,
      CFPP, kinematic viscosity at 40 degrees C and density at 15 degrees C of
      biodiesel.
AB  - Biodiesel is one of the main alternatives to fossil diesel. It is a non-toxic
      renewable resource, which leads to lower emissions of polluting gases. In fact,
      European governments are targeting the incorporation of 20% of biofuels in the
      fossil fuels until 2020. Chemically, biodiesel is a mixture of fatty acid methyl
      esters, derived from vegetable oils or animal fats, which is usually produced by
      a transesterification reaction, where the oils or fats react with an alcohol, in
      the presence of a catalyst. The European Standard (EN 14214) establishes 25
      parameters that have to be analysed to certify biodiesel quality and the
      analytical methods that should be used to determine those properties. This work
      reports the use of near infrared (NIR) spectroscopy to determine some important
      biodiesel properties: the iodine value, the cold filter plugging point, the
      kinematic viscosity at 40 degrees C and the density at 15 degrees C. Principal
      component analysis was used to perform a qualitative analysis of the spectra and
      partial least squares regression to develop the calibration models between
      analytical and spectral data. The results support that NIR spectroscopy, in
      combination with multivariate calibration, is a promising technique applied to
      biodiesel quality control, in both laboratory and industrial-scale samples.

PMID- 18804613
TI  - Identification of polyoxypregnane glycosides from the stems of Marsdenia
      tenacissima by high-performance liquid chromatography/tandem mass spectrometry.
AB  - A facile method based on high-performance liquid chromatography coupled with
      electrospray ionization tandem mass spectrometry (HPLC/(+)ESI-MS(n)) has been
      established for the analysis of polyoxypregnane glycosides in the stems of
      Marsdenia tenacissima. The data reveals the ability of MS(n) in the structural
      elucidation of polyoxypregnane glycosides including the nature of the
      polyoxypregnane core, the kinds of the substituents and the types of sugar
      residues. Offline Fourier transform ion cyclotron resonance mass spectrometry
      (FTICR-MS) is also performed to assign accurate elemental compositions. In this
      study, eighteen polyoxypregnane glycosides have been investigated. Among these
      components, five compounds are unambiguously identified as Marsdenoside K,
      Tencissoside A, B, C and D; two compounds are established as novel compounds
      based on mass spectral data; and the other eleven compound's structures are
      tentatively proposed. Furthermore, breakdown curves are constructed to
      distinguish five pairs of isomers among these eighteen compounds. As far as our
      knowledge, this is the first report on identification of polyoxypregnane
      glycosides in the stems of M. tenacissima by HPLC/ESI-MS(n) directly, which could
      save time and material consuming efforts in traditional phytochemistry analyses.

PMID- 18804614
TI  - Partition of horseradish peroxidase with maintained activity in aqueous biphasic
      system based on ionic liquid.
AB  - Enzyme activity and partition behavior in aqueous biphasic systems (ABSs)
      consisting of ionic liquid (IL) and salt (IL-ABSs) were investigated to increase
      our understanding of IL-ABSs and shed light on their application potential as
      enzyme extraction system. With horseradish peroxidase (HRP) as the model enzyme,
      several effects of alkylimidazolium chloride-K(2)HPO(4) ABSs on activity and
      partition behavior of enzyme were studied including alkyl chain length of ILs and
      concentrations of each component. High lyotropic ILs (1-butyl-3-methylimidazolium
      and 1-ethyl-3-methylimidazolium chloride) and adequate water content (>40%) were
      both essential for the activity maintenance of HRP in IL-ABS. 1-Butyl-3
      methylimidazolium chloride ([C(4)mim]Cl) was found to be an appropriate IL for
      phase forming and HRP activity retaining. After optimization of phase condition,
      about 80% HRP amount was distributed in the IL-rich upper phase, and greater than
      90% enzyme activity was obtained. Moreover, compared with the commonly used
      polymer-based ABSs, this [C(4)mim]Cl-ABS has a much lower viscosity, which is
      very beneficial to the experimental operation. Therefore, the tested IL-ABS could
      be considered as a potential enzyme extraction system.

PMID- 18804615
TI  - A novel evanescent wave scattering imaging method for single gold particle
      tracking in solution and on cell membrane.
AB  - We propose a novel evanescent wave scattering imaging method using an objective
      type total internal reflection system to image and track single gold
      nanoparticles (GNPs) in solution. In this imaging system, only a millimeter-scale
      hole is employed to efficiently separate GNPs scattering light from the
      background reflected beam. The detailed experimental realization of the imaging
      system was discussed, and the effect of the hole size on imaging was
      investigated. We observed that the hole diameters from 2.5 to 4mm are suitable to
      perform the scattering imaging by adjusting the incidence angle. The technology
      was successfully applied to track single gold nanoparticles in solution and on
      live cell membrane via the anti-epidermal growth factor receptor antibody.
      Compared to total internal fluorescence microscopy, the resonance light
      scattering detection has no photobleaching or blinking inherent to fluorescent
      dyes and quantum dots. Compared to conventional dark-field microscopy, the
      evanescent wave illumination can be conveniently applied to study membrane
      dynamics in living cells. Additionally, the objective-based configuration
      provides a free space above the coverslip, and allows imaging and concomitant
      manipulation of live cells in culture by microinjection, patch-clamping, AFM and
      other techniques.

PMID- 18804616
TI  - Determination of cadmium, lead, copper and zinc in the acetic acid extract of
      glazed ceramic surfaces by anodic stripping voltammetric method.
AB  - An anodic stripping voltammetric method has been developed for determination of
      cadmium, lead, copper and zinc in acetic acid extract of glazed ceramic surfaces.
      An aliquot of 4% (v/v) acetic acid solution was kept in a ceramic ware for 24h in
      the dark, then 10 mL of the extracted solution was placed in a voltammetric cell.
      The solution was purged with oxygen free nitrogen gas for 3 min before deposition
      of the metals was carried out by applying a constant potential of -1.20 V versus
      Ag/AgCl to the hanging mercury drop electrode (HMDE) for 45 s. A square wave
      waveform was scanned from -1.20 to 0.15 V and a voltammogram was recorded. A
      standard addition procedure was used for quantification. Detection limits of
      0.25, 0.07, 2.7 and 0.5 microg L(-1) for cadmium, lead copper and zinc,
      respectively, were obtained. Relative standard deviations for 11 replicate
      determinations of 100 microg L(-1) each of all the metals were in the range of
      2.8-3.6%. Percentage recoveries obtained by spiking 50 microg L(-1) of each metal
      to the sample solution were in the range of 105-113%. The method was successfully
      applied to ceramic wares producing in Lampang province of Thailand. It was found
      that the contents of cadmium, lead, copper and zinc released from the samples
      were in the range of <0.01-0.16, 0.02-0.45, <0.14 and 0.28-10.36 microg dm(-2),
      respectively, which are lower than the regulated values of the Thai industrial
      standard. The proposed method is simpler, more convenient and more sensitive than
      the standard method based on FAAS.

PMID- 18804617
TI  - Fluorescence resonance energy transfer between acridine orange and rhodamine 6G
      and its analytical application for vitamin B12 with flow-injection laser-induced
      fluorescence detection.
AB  - By coupling flow-injection with laser-induced fluorescence detection, a setup was
      developed and a novel method combining fluorescence resonance energy transfer
      (FRET) and flow-injection analysis (FIA) was proposed for the determination of
      vitamin B(12) (VB(12)) based on its fluorescence quenching on the system of
      acridine orange (AO)/rhodamine 6G (R6G). The effective energy transfer could
      occur between AO and R6G in the dodecyl benzene sodium sulfonate (DBS) while
      454nm argon laser was used as the excitation source, and as a result, the
      fluorescence emission of R6G has been increased significantly. It was found that
      the fluorescence of the above system could be sharply diminished by VB(12). By
      using the mixed solution AO-R6G-DBS and the same solution containing VB(12) as
      the carrier and sample, respectively, a series of negative peaks which could be
      applied for the quantification of VB(12) were obtained. The detection limit for
      VB(12) was 1.65x10(-6)mol/L. The linear range for determining VB(12) was 4x10(-4)
      to 2x10(-6)mol/L (correlation coefficient, r=0.9923). The method was applied to
      measure VB(12) injections with satisfactory results.

PMID- 18804618
TI  - Identification of individual DNA molecule of Mycobacterium tuberculosis by nested
      PCR-RFLP and capillary electrophoresis.
AB  - The improvement of sensitivity and differentiation in rapidly identifying a small
      amount of mycobacteria in sputum has significant implications for reducing
      tuberculosis transmission. We previously applied the conventional PCR and
      capillary electrophoresis (CE) to establish the restriction fragment length
      polymorphism (RFLP) pattern of mycobacterial 65-kDa heat shock protein (hsp65)
      gene from colony specimens. However, the previous analysis did not provide enough
      sensitivity for sputum specimens in which the limitation of analysis might be
      hindered by PCR inhibitors and primer-dimers formation during amplification. In
      the current study, nested PCR (nPCR) had been redesigned for PCR-RFLP analysis
      (PRA) of mycobacterial hsp65 gene using CE. The results show both Mycobacterium
      tuberculosis complex and mycobacteria other than tuberculosis could be identified
      in the presence of PCR inhibitors. The interference due to primer-dimers was also
      minimized. Based on the Poisson distribution, the repeatability of single DNA
      molecule detection was greatly affected by sampling probability and might be
      improved significantly by increasing the sample loading. The PRA using nPCR and
      CE is not only able to detect the individual mycobacterial DNA molecule but also
      potentially differentiate the species.

PMID- 18804619
TI  - Speciated isotope dilution analysis of Cr(III) and Cr(VI) in water by ICP-DRC-MS.
AB  - An isotope dilution method has been developed for the speciation analysis of
      chromium in natural waters which accounts for species interconversions without
      the requirement of a separation instrument connected to the mass spectrometer.
      The method involves (i) in-situ spiking of the sample with isotopically enriched
      chromium species; (ii) separation of chromium species by precipitation with iron
      hydroxide; (iii) careful measurement of isotope ratios using an inductively
      coupled plasma mass spectrometer (ICP-MS) with a dynamic reaction cell (DRC) to
      remove isobaric polyatomic interferences. The method detection limits are 0.4
      microg L(-1) for Cr(III) and 0.04 microg L(-1) for Cr(VI). The method is
      demonstrated for the speciation of Cr(III) and Cr(VI) in local nullah and
      synthetically spiked water samples. The percentage of conversion from Cr(III) to
      Cr(VI) increased from 5.9% to 9.3% with increase of the concentration of Cr(VI)
      and Cr(III) from 1 to 100 microg L(-1), while the reverse conversion from Cr(VI)
      to Cr(III) was observed within a range between 0.9% and 1.9%. The equilibrium
      constant for the conversion was found to be independent of the initial
      concentrations of Cr(III) and Cr(VI) and in the range of 1.0 (at pH 3) to 1.8 (at
      pH 10). The precision of the method is better than that of the DPC method for
      Cr(VI) analysis, with the added bonuses of freedom from interferences and
      simultaneous Cr(III) determination.

PMID- 18804620
TI  - Comparison of solvent mixtures for pressurized solvent extraction of soil fatty
      acid biomarkers.
AB  - The extraction and transesterification of soil lipids into fatty acid methyl
      esters (FAMEs) is a useful technique for studying soil microbial communities. The
      objective of this study was to find the best solvent mixture to extract soil
      lipids with a pressurized solvent extractor system. Four solvent mixtures were
      selected for testing: chloroform:methanol:phosphate buffer (1:2:0.8, v/v/v),
      chloroform:methanol (1:2, v/v), hexane:2-propanol (3:2, v/v) and acetone. Soils
      were from agricultural fields and had a wide range of clay, organic matter and
      microbial biomass contents. Total lipid fatty acid methyl esters (TL-FAMEs) were
      the extractable soil lipids identified and quantified with gas chromatography and
      flame ionization detection. Concentrations of TL-FAMEs ranged from 57.3 to 542.2
      nmole g(-1) soil (dry weight basis). The highest concentrations of TL-FAMEs were
      extracted with chloroform:methanol:buffer or chloroform:methanol mixtures than
      with the hexane:2-propanol or acetone solvents. The concentrations of TL-FAMEs in
      chemical groups, including saturated, branched, mono- and poly-unsaturated and
      hydroxy fatty acids were assessed, and biological groups (soil bacteria,
      mycorrhizal fungi, saprophytic fungi and higher plants) was distinguished. The
      extraction efficiency for the chemical and biological groups followed the general
      trend of: chloroform:methanol:buffer> or =chloroform:methanol>hexane:2
      propanol=acetone. Discriminant analysis revealed differences in TL-FAME profiles
      based on the solvent mixture and the soil type. Although solvent mixtures
      containing chloroform and methanol were the most efficient for extracting lipids
      from the agricultural soils in this study, soil properties and the lipid groups
      to be studied should be considered when selecting a solvent mixture. According to
      our knowledge, this is the first report of soil lipid extraction with hexane:2
      propanol or acetone in a pressurized solvent extraction system.

PMID- 18804621
TI  - FTIR-multivariate curve resolution monitoring of photo-Fenton degradation of
      phenolic aqueous solutions. Comparison with HPLC as a reference method.
AB  - A new analytical method based on Fourier transformed infrared spectroscopy (FTIR)
      using chemometric tools to treat spectral data is proposed to study the
      degradation of aqueous phenolic solutions by photo-Fenton process. Obtained
      results were validated by high-performance liquid chromatography (HPLC) taken as
      a reference method. First a discrimination of the different steps of phenol
      degradation was possible by applying a principal component analysis (PCA). Then a
      description of the reaction evolution was successfully made using MCR-ALS, a
      multivariate curve resolution method which has permitted to obtain the
      concentration profiles of phenol and its photoproducts. Kinetics of their
      formation and disappearance described with this new approach are in agreement
      with HPLC results. This methodology may be a good alternative to classical
      analyses for monitoring of the degradation reactions because a lot of data are
      recorded and treated simultaneously. It shows how species concentration varies
      over time, informing thus on the reaction mechanism because a structural
      identification of products is possible through pure extracted spectra.

PMID- 18804622
TI  - Use of biotin-streptavidin system for developing a viable, sensitive and specific
      antigen heterologous assay for hapten.
AB  - The present study demonstrates improvement in sensitivity and specificity of
      hapten assay by using antigen heterology in conjunction with low molecular weight
      biotin label as compared to high molecular weight horseradish peroxidase (HRP)
      label. For generation of antiserum, cortisol-3-O-carboxylmethyl-oxime-bovine
      serum albumin (F-3-CMO-BSA) was used as immunogen whereas, for the preparation of
      primary label, corticosterone-3-carboxymethyl oxime (B-3-CMO) was coupled with
      biotinylcaproylhydrazide and HRP by employing N-hydroxysuccinimide mediated
      carbodiimide reaction. The data of the present study revealed that the antigen
      heterologous assay which employed high molecular weight HRP label showed 100%
      cross-reaction with corticosterone. On the contrary, when HRP was replaced with
      low molecular weight biotin label, less than 0.1% cross-reaction was observed
      with all analogous C(18), C(19), C(21) and C(27) steroids including
      corticosterone (0.2%). Moreover, the sensitivity of the later assay was 0.09
      microg/dL, which is appreciable as compared to previously reported enzyme based
      assays. The recovery of the exogenously spiked serum pools lies in the range of
      90.3-104.2%. The intra-assay and inter-assay coefficient of variation (CVs)
      ranged from 3.3% to 7.8% and 2.3% to 7.7%, respectively. The serum cortisol
      values obtained by this method correlated well with those obtained by
      radioimmunoassay; r=0.9 (n=50). The use of much stable biotin label in place of
      HRP has made the antigen heterologous enzyme linked immunosorbent assay (ELISA)
      of cortisol assay highly specific and sensitive.

PMID- 18804623
TI  - Alumina sol-gel/sonogel-carbon electrode based on acetylcholinesterase for
      detection of organophosphorus pesticides.
AB  - Two new amperometric biosensors based on immobilization of acetylcholinesterase
      on a sonogel-carbon electrode for detection of organophosphorous compounds are
      proposed. The electrodes were prepared applying high-energy ultrasounds directly
      to the precursors. The first biosensor was obtained by simple entrapping
      acetylcholinesterase in Al(2)O(3) sol-gel matrix on the sonogel-carbon. The
      second biosensor was produced in a sandwich configuration. Its preparation
      involved adsorption of the enzyme and modification via a polymeric membrane such
      as polyethylene glycol and the ion-exchanger Nafion. The optimal enzyme loading
      was found to be 0.7 mIU. Both biosensors showed optimal activity in 0.2 M
      phosphate buffer, pH 7.0, at an operating potential of 210 mV. The detection
      limit achieved for chlorpyriphos-ethyl-oxon was 2.5x10(-10)M at a 10-min
      incubation time.

PMID- 18804624
TI  - A novel biamperometric biosensor for urinary oxalate determination using flow
      injection analysis.
AB  - A biosensor for determination of oxalate concentration in urine has been
      developed by immobilisation of oxalate oxidase and peroxidase on the surface of
      an interdigitated gold electrode. Enzyme immobilisation was performed using BSA
      and glutaraldehyde. Biamperometric measurements were made in flow conditions both
      in aqueous oxalate solutions (tested concentration range between 50 microM and 10
      mM) and in real urine samples (tested measuring range between 5 and 100 microM).
      Optimal working conditions were examined for flow-injection analysis, and good
      correlation was achieved between added oxalate quantity and the one measured by
      biosensor in urine matrix (R(2)=0.9983). The influence of some interferences
      (ascorbic acid, uric acid, paracetamol, acetylsalicylic acid) was also studied
      using biamperometric measurement mode.

PMID- 18804625
TI  - Determination of lecithin and soybean oil in dietary supplements using partial
      least squares-Fourier transform infrared spectroscopy.
AB  - Lecithin and soybean oil in dietary supplements were determined by Fourier
      transform infrared spectrometry transmission measurements in dichloromethane in
      combination with a partial least squares (PLS) regression. Two different PLS
      models were developed, using 16 synthetic mixtures of analytes in
      dichloromethane, making measurements in the spectral range from 931.8 to 1252.3
      cm(-1) for lecithin and from 911.4 to 1246.9 cm(-1) and 1695.3 to 1774.5 cm(-1)
      for soybean oil. Seven products from the Spanish market with lecithin
      concentrations between 21.1% and 99.1% and soybean oil concentrations between 0%
      and 37.2% were analyzed by the proposed method and the data was compared to a
      chromatographic reference procedure obtaining accurate results. For samples
      spiked with amounts between 50 and 250 mg of lecithin and soybean oil recovery
      percentages between 98.0% and 102.1% and between 93.6% and 102.0% with an average
      precision of 0.35% and 0.41% were achieved for lecithin and soybean oil,
      respectively. This method can be applied for the quality control of dietary
      supplements.

PMID- 18804626
TI  - Application of thin-shielded mercury microelectrodes in anodic stripping
      voltammetry.
AB  - The performance in anodic stripping voltammetry (ASV) of hemispherical mercury
      microelectrodes, fabricated by electrodeposition of liquid mercury on the surface
      of Pt microdisks which were surrounded by a rather thick or thin insulating
      shield, was compared. The Pt microdisks were produced by sealing a wire of 25
      microm diameter into a glass capillary, and by coating the cylindrical length of
      the Pt wire with a cathodic electrophoretic paint. The ratio of the overall tip
      radius b, to the basal radius of the electrode a, so-called RG=b/a, was equal to
      110+/-10 and 1.52+/-0.01 for the thick- and thin-shielded microdisk,
      respectively. The mercury microelectrodes were characterized by cyclic
      voltammetry at 1 mVs(-1), in 1mM Ru(NH(3))(6)(3+) aqueous solution. The steady
      state voltammogram recorded with the thin-shielded mercury microelectrode
      displayed less hysteresis, while the steady-state current was about 30% higher
      than that of the thicker one. This was a consequence of the additional flux due
      to diffusion from behind the plane of the electrode. The flux enhancement, which
      was operative at the thin-shielded mercury microelectrode during the deposition
      step in the ASV experiments, allowed recording stripping peaks for Cd and Pb,
      which resulted about 32% larger than those recorded at the thicker shielded
      mercury microelectrode, under same experimental conditions. The usefulness of the
      thin-shielded mercury microelectrode for ASV measurements in real samples was
      verified by determining the content of heavy metal ions released in the pore
      water (pH 4.5) of a soil slurry.

PMID- 18804627
TI  - Urea as new stabilizing agent for imipenem determination: electrochemical study
      and determination of imipenem and its primary metabolite in human urine.
AB  - Imipenem shows a fast chemical conversion to a more stable imin form (identical
      to that of biochemical dehydropeptidase degradation) in aqueous solutions and
      stabilizing agents used avoid its electrochemical study and determination. The
      aim of this work is the proposal of urea as stabilizing agent which allows the
      electrochemical study of imipenem and the proposal of electrochemical methods for
      the determination of imipenem and its primary metabolite (M1) in human urine
      samples. Electrochemical studies were realized in phosphate buffer solutions over
      pH range 1.5-8.0 using differential-pulse polarography, DC-tast polarography,
      cyclic voltammetry and adsorptive stripping voltammetry. In acidic media, a non
      reversible diffusion-controlled reduction involving a two steps mechanism which
      involves one electron and one proton in the first step and two electrons and two
      protons in the second step occurs and the mechanism for the reduction was
      suggested. A differential-pulse polarographic method for the determination of
      imipenem in the concentration range 3.2x10(-6) to 2x10(-5)M (0.95-3.4 mg/L) and
      its primary metabolite in the concentration range 1.4x10(-6) to 10(-4)M (0.43
      26.1 mg/L) with detection limits of 9.6x10(-7)M (0.28 microg/L imipenem) and
      4.3x10(-7)M (0.14 microg/L M1) was proposed. Also, a method based on controlled
      adsorptive pre-concentration of imipenem on the hanging mercury drop electrode
      followed by voltammetric measure, allows imipenem determination in the
      concentration range 1.8x10(-8) to 1.2x10(-6)M (5.42-347 microg/L) with a
      detection limit of 5.4x10(-9)M (1.63 microg/L). The proposed methods have been
      used for the direct determination of the analytes in a pharmaceutical formulation
      and human urine.

PMID- 18804628
TI  - Characterization of a distributed plasma ionization source (DPIS) for ion
      mobility spectrometry and mass spectrometry.
AB  - A recently developed atmospheric pressure ionization source, a distributed plasma
      ionization source (DPIS), was characterized and compared to commonly used
      atmospheric pressure ionization sources with both mass spectrometry (MS) and ion
      mobility spectrometry (IMS). The source consisted of two electrodes of different
      sizes separated by a thin dielectric. Application of a high RF voltage across the
      electrodes generated plasma in air yielding both positive and negative ions.
      These reactant ions subsequently ionized the analyte vapors. The reactant ions
      generated were similar to those created in a conventional point-to-plane corona
      discharge ion source. The positive reactant ions generated by the source were
      mass identified as being solvated protons of general formula (H(2)O)(n)H(+) with
      (H(2)O)(2)H(+) as the most abundant reactant ion. The negative reactant ions
      produced were mass identified primarily as CO(3)(-), NO(3)(-), NO(2)(-), O(3)(-)
      and O(2)(-) of various relative intensities. The predominant ion and relative ion
      ratios varied depending upon source construction and supporting gas flow rates. A
      few compounds including drugs, explosives and amines were selected to evaluate
      the new ionization source. The source was operated continuously for 3 months and
      although surface deterioration was observed visually, the source continued to
      produce ions at a rate similar that of the initial conditions.

PMID- 18804629
TI  - Laser-induced breakdown spectroscopy for simultaneous determination of Sm, Eu and
      Gd in aqueous solution.
AB  - This paper reports studies on the determination of trace levels of samarium,
      europium and gadolinium in aqueous samples by laser-induced breakdown
      spectroscopy (LIBS). In this work, a membrane-based filter paper was used as a
      sample support for the liquid samples. The laser-induced plasma was produced in
      air at atmospheric pressure, using a pulsed Nd:YAG laser. Calibration standards
      and synthetic mixtures of these lanthanides were prepared using solutions
      prepared from respective high purity oxides. Linear calibration was obtained for
      Sm, Eu and Gd by normalizing the intensities of lanthanides emission lines with
      respective to C(I) 193.029 nm emission line. The concentrations of Sm, Eu and Gd
      were then determined in a solution containing a mixture of these lanthanides. The
      concentrations of individual lanthanides were obtained within 5% of the expected
      values. Limits of detection were found to be 1.3 ppmw (Sm), 1.9 ppmw (Eu) and 2.3
      ppmw (Gd).

PMID- 18804630
TI  - Visualized investigation of yeast transformation induced with Li+ and
      polyethylene glycol.
AB  - The effects of Li(+) and polyethylene glycol (PEG) on the genetic transformation
      of Saccharomyces cerevisiae were investigated by using fluorescence microscopy
      (FM) to visualize the binding of plasmid DNA labeled with YOYO-1 to the surface
      of yeast cells, scanning electron microscopy (SEM) and atomic force microscopy
      (AFM) to image the change in surface topography of yeast cells, coupled with
      transformation frequency experiments. The results showed that under the same
      conditions, the transformation frequencies of yeast protoplasts were much higher
      than those of intact yeast cells. PEG was absolutely required for the binding of
      DNA to the surface of intact yeast cells or yeast protoplasts, and had no effect
      on the surface topography of intact yeast cells or yeast protoplasts. In the
      presence of PEG, Li(+) could greatly enhance the binding of plasmid DNA to the
      surface of intact yeast cells, increase their transformation frequency, and
      affect their surface topography. On the other hand, no effect on the DNA binding
      to the surface of protoplasts and no increase in the number of transformants and
      no surface topography changes were found upon the treatment with Li(+) to
      protoplasts. In the present work, the effects of Li(+) and PEG on yeast genetic
      transformation were directly visualized, rather than those deduced from the
      results of transformation frequencies. These results indicate that cell wall
      might be a barrier for the uptake of plasmid DNA. Li(+) could increase the
      permeability of yeast cell wall, then increase the exposed sites of DNA binding
      on intact yeast cells. The main role of PEG was to induce DNA binding to cell
      surface.

PMID- 18804631
TI  - Improved microfluidic chip-based sequential-injection trapped-droplet array
      liquid-liquid extraction system for determination of aluminium.
AB  - An improved microfluidic chip-based sequential-injection trapped-droplet array
      liquid-liquid extraction system with chemiluminescence (CL) detection was
      developed in this work. Two recess arrays were fabricated on both sides of the
      extraction channel to produce droplet arrays of organic extractant. A chip
      integrated monolithic probe was fabricated at the inlet of the extraction channel
      on the glass chip instead of the capillary probe connected to the microchannel,
      in order to improve the system stability and reliability. A slotted-vial array
      system coupled with the monolithic probe was used to sequentially introduce
      sample and different solvents and reagents into the extraction channel for
      extraction and CL detection. The performance of the system was demonstrated in
      the determination of Al(3+) using Al(3+)-dihydroxyazobenzene (DHAB) and tributyl
      phosphate (TBP) extraction system. The operation conditions, including extraction
      time, concentration and flow rate of the CL reagents, were optimized. Within one
      analysis cycle of 12 min, an enrichment factor of 85 was obtained in the
      extraction stage with a sample consumption of 1.8 microL. The consumption of CL
      reagent, bis(2-carbopentyloxy-3,5,6-trichlorophenyl)oxalate (CPPO), was 120
      nL/cycle. The detection limit of the system for Al(3+) was 1.6x10(-6)mol/L with a
      precision of 4.5% (R.S.D., n=6).

PMID- 18804632
TI  - Rational design of a colorimetric and ratiometric fluorescent chemosensor based
      on intramolecular charge transfer (ICT).
AB  - A simple colorimetric and ratiometric fluorescent anion sensor 1, 3,6-dichloro
      1,8-dinitrocarbazole, was rationally designed and synthesized on basis of the
      mechanism of intramolecular charge transfer (ICT). In DMSO solutions of 1, the
      presence of AcO(-), F(-) and H(2)PO(4)(-) gave birth to the formation of a 2:1
      host-to-guest complex, which was synchronously accompanied by a 'naked-eye' color
      change from light yellow to purple, a red-shift of the absorption spectrum and a
      blue-shift of the emission spectrum.

PMID- 18804633
TI  - Sensitive determination of anions in saliva using capillary electrophoresis after
      transient isotachophoretic preconcentration.
AB  - A transient isotachophoresis-capillary electrophoresis (tITP-CE) system for the
      determination of minor inorganic anions in saliva is described. The complete
      separation and quantification of bromide, iodide, nitrate, nitrite, and
      thiocyanate has been achieved with only centrifugation and dilution of the saliva
      sample. In-line tITP preconcentration conditions, created by introduction of the
      plugs of 5 mM dithionic acid (leading electrolyte) and 10 mM formic acid
      (terminating electrolyte) before and after the sample zone, respectively, allowed
      the limits of direct UV absorption detection (at 200 nm) to be up to 50-fold
      improved as compared with CE without tITP. As a result, nitrate and thiocyanate
      were still detectable at 4.6 and 3.8 microgl(-1), respectively, in 1000 times
      diluted saliva. The daily variations of anionic concentrations in saliva samples
      taken from a smoking health volunteer were discussed based on the results of tITP
      CE analysis. It was confirmed that the thiocyanate concentration in saliva
      noticeably increased after smoking. This is apparently the first report on
      simultaneous quantification of more than four anionic salivary constituents using
      CE.

PMID- 18804634
TI  - Comparison of microwave-assisted digestion procedures for total trace element
      content determination in calcareous soils.
AB  - The aim of the study was to determine total trace (Cd, Co, Cr, Cu, Mn, Pb and Zn)
      and major (Al and Fe) element concentrations in calcareous soils using microwave
      assisted digestion procedures. The literature showing lack of consensus regarding
      digestion procedures and unsatisfying recoveries for calcareous materials, four
      procedures using various acid combinations (HCl, HNO(3), H(2)O(2), HF) and
      volumes were tested using a certified reference material (CRM 141R) and natural
      calcareous soil samples. Digests were analysed by inductively coupled plasma
      atomic emission spectrometry (ICP-AES). Repeatability (R.S.D. <5%) and recoveries
      (82-116%) showed that the procedures were precise and accurate for most elements.
      Five calcareous soil samples from a Champagne vineyard plot were, then, subjected
      to these procedures. In calcareous materials, the presence of HF resulted in Al
      being severely underestimated (recovery <5%) and Co overestimated (recovery
      >124%) due to complex formation or spectrochemical interferences, respectively.
      As digestion was not significantly influenced by the addition of H(2)O(2), the
      procedure corresponding to Aqua regia (HCl-HNO(3)) appeared as the best
      compromise and was selected for further multielemental environmental studies on
      calcareous materials, even if the absence of HF could lead to incomplete
      digestion of accessory silicate minerals. Results for a vineyard plot showed that
      the soils were contaminated (3.65 mg kg(-1) Cd, 67 mg kg(-1) Cr, 278 mg kg(-1)
      Cu, 143 mg kg(-1) Pb and 400 mg kg(-1) Zn) as a consequence of urban waste and
      copper-treatment applications.

PMID- 18804635
TI  - Ligandless cloud point extraction of Cr(III), Pb(II), Cu(II), Ni(II), Bi(III),
      and Cd(II) ions in environmental samples with Tween 80 and flame atomic
      absorption spectrometric determination.
AB  - A cloud point extraction (CPE) procedure has been developed for the determination
      trace amounts of Cr(III), Pb(II), Cu(II), Ni(II), Bi(III), and Cd(II) ions by
      using flame atomic absorption spectrometry. The proposed cloud point extraction
      method was based on cloud point extraction of analyte metal ions without ligand
      using Tween 80 as surfactant. The surfactant-rich phase was dissolved with 1.0 mL
      1.0 mol L(-1) HNO(3) in methanol to decrease the viscosity. The analytical
      parameters were investigated such as pH, surfactant concentration, incubation
      temperature, and sample volume, etc. Accuracy of method was checked analysis by
      reference material and spiked samples. Developed method was applied to several
      matrices such as water, food and pharmaceutical samples. The detection limits of
      proposed method were calculated 2.8, 7.2, 0.4, 1.1, 0.8 and 1.7 microg L(-1) for
      Cr(III), Pb(II), Cu(II), Ni(II), Bi(III), and Cd(II), respectively.

PMID- 18804636
TI  - Determination of asulam by fast stopped-flow chemiluminescence inhibition of
      luminol/peroxidase.
AB  - An efficient, sensitive and fast stopped-flow method has been developed to
      determine asulam in water, based on its inhibition effect on the horseradish
      peroxidase-luminol-hydrogen peroxide chemiluminescence reaction, (HRP-luminol
      H(2)O(2)). Ultra fast data acquisition (0.20s) facilitates excellent selectivity
      because no interferences from concomitants in the matrix act in such short time
      scale. The precision as repeatability (expressed as relative standard deviation,
      n=10) was 0.4% at a 40 pM level. The detection limit was 1.5 pM (0.35 ng/L) and
      7.15 pM in pure and raw water, respectively. The calibration data over the range
      5-60 pM present a correlation coefficient of r=0.9993. The proposed method has
      been applied to determine asulam in water samples by using solid-phase extraction
      (SPE). Mean recovery value was 98.1+/-2% at 50 pM level.

PMID- 18804637
TI  - Development and validation of a rapid multiresidue method for pesticide
      determination using gas chromatography-mass spectrometry: a realistic case in
      vineyard soils.
AB  - A rapid and simultaneous method for residue identification and quantification for
      seven pesticides in agricultural soils has been developed to study a realistic
      situation in vineyard. The target compounds are two insecticides, two herbicides
      and three fungicides, from different chemical families. The procedure is based on
      a pressurized liquid extraction (PLE) with acetone, before a multiresidue GC-MS
      analysis. The recovery of PLE is between 53.8+/-2.4 and 99.9+/-4.4% according to
      pesticide. A limit of detection (LOD) between 1.4 and 4.6 microg kg(-1) of dry
      soil was obtained for five analytes. This procedure for testing soil
      contamination is sensitive and easy to perform.

PMID- 18804638
TI  - Combined HPLC-CUPRAC (cupric ion reducing antioxidant capacity) assay of parsley,
      celery leaves, and nettle.
AB  - This study aims to identify the essential antioxidant compounds present in
      parsley (Petroselinum sativum) and celery (Apium graveolens) leaves belonging to
      the Umbelliferae (Apiaceae) family, and in stinging nettle (Urtica dioica)
      belonging to Urticaceae family, to measure the total antioxidant capacity (TAC)
      of these compounds with CUPRAC (cupric ion reducing antioxidant capacity) and
      ABTS spectrophotometric methods, and to correlate the TAC with high performance
      liquid chromatography (HPLC) findings. The CUPRAC spectrophotometric method of
      TAC assay using copper(II)-neocuproine (2,9-dimethyl-1,10-phenanthroline) as the
      chromogenic oxidant was developed in our laboratories. The individual antioxidant
      constituents of plant extracts were identified and quantified by HPLC on a C18
      column using a modified mobile phase of gradient elution comprised of MeOH-0.2% o
      phosphoric acid and UV detection for polyphenols at 280 nm. The TAC values of
      HPLC-quantified antioxidant constituents were found, and compared for the first
      time with those found by CUPRAC. The TAC of HPLC-quantified compounds accounted
      for a relatively high percentage of the observed CUPRAC capacities of plant
      extracts, namely 81% of nettle, 60-77% of parsley (in different hydrolyzates of
      extract and solid sample), and 41-57% of celery leaves (in different
      hydrolyzates). The CUPRAC total capacities of the 70% MeOH extracts of studied
      plants (in the units of mmol trolox g(-1)plant) were in the order: celery
      leaves>nettle>parsley. The TAC calculated with the aid of HPLC-spectrophotometry
      did not compensate for 100% of the CUPRAC total capacities, because all flavonoid
      glycosides subjected to hydrolysis were either not detectable with HPLC, or not
      converted to the corresponding aglycons (i.e., easily detectable and quantifiable
      with HPLC) during the hydrolysis step.

PMID- 18804639
TI  - Study of the electrochemical behavior of isorhamnetin on a glassy carbon
      electrode and its application.
AB  - The electrochemical behavior of isorhamnetin (ISO) at a glassy carbon electrode
      was studied in a phosphate buffer solution (PBS) of pH 4.0 by cyclic voltammetry
      (CV) and differential pulse voltammetric method (DPV). A well-defined redox wave
      of ISO involving one electrons and one proton appeared. The electrode reaction is
      a reactant weak adsorption-controlled process with a charge transfer coefficient
      (alpha) of 0.586. Based on the understanding of the electrochemical process of
      ISO at the glassy carbon electrode, analysis of ISO can be realized. Under
      optimal conditions, the oxidation peak current showed linear dependence on the
      concentration of ISO in the range of 1.0x10(-8) to 4.0x10(-7)M and 1.0x10(-6) to
      1.0x10(-5)M. The detection limit is 5.0x10(-9)M. This method has been
      successfully applied to the detection of ISO in tablets.

PMID- 18804640
TI  - Sensitive and selective detection of aspartic acid and glutamic acid based on
      polythiophene-gold nanoparticles composite.
AB  - In recent years, gold nanoparticles and water-soluble fluorescent conjugated
      polymers are promising materials in terms of their potential applications in a
      variety of fields, ranging from monitoring DNA hybridization to demonstrate the
      interaction between proteins, or detecting diseased cell, metal ions and small
      biomolecular. In order to exploit some new properties of the both, many attempts
      have been devoted to achieve nanoparticle-polymer composite via incorporating
      metal nanoparticle into polymer or vice versa, however, only few of them are put
      into practical application. In the present paper, we utilize the "superquenching"
      property of AuNPs to polythiophene derivatives for detecting aspartic acid (Asp)
      and glutamic acid (Glu) in pure water, and discuss the factors accounting for
      fluorescence quenching and recovery via modulating pH. Thus an exceptionally
      simple, rapid and sensitive method for detecting Asp and Glu is established with
      a limit of detection (LOD) is 32 nM for Asp and 57 nM for Glu, the linear range
      of determination for Asp is 7.5x10(-8)M to 6x10(-6)M and 9.0x10(-8)M to 5x10(-6)M
      for Glu. The system is applied to real sample detection and the results are
      satisfying. Otherwise the composite is very sensitive to pH change of solution,
      we expect it will be possible to use as pH sensor with wide range in the future.

PMID- 18804641
TI  - Sensitive voltammetric determination of rutin at an ionic liquid modified carbon
      paste electrode.
AB  - An ionic liquid modified carbon paste electrode (IL/CPE) had been fabricated by
      using hydrophilic ionic liquid 1-amyl-3-methylimidazolium bromide ([AMIM]Br) as a
      modifier. The IL/CPE was characterized by scanning electron microscope and
      voltammetry. Electrochemical behavior of rutin at the IL/CPE had been
      investigated in pH 3.29 Britton-Robinson (B-R) buffer solution by cyclic
      voltammetry (CV) and square wave voltammetry (SWV). The experimental results
      suggested that the modified electrode exhibited an electrocatalytic activity
      toward the redox of rutin. The electron transfer coefficient (alpha) and the
      standard rate constant (k(s)) of rutin at the modified electrode were calculated.
      Under the selected conditions, the reduction peak current was linearly dependent
      on the concentration of rutin in the range of 4.0x10(-8) to 1.0x10(-5)mol L(-1)
      (r=0.9998), with a detection limit of 1.0x10(-8)mol L(-1)(S/N=3). The relative
      standard deviation (R.S.D.) for six times successful determination of 8.0x10(
      7)mol L(-1) rutin was 1.2%. The proposed method was applied to determine rutin in
      tablet and urine sample. In addition, the IL/CPE exhibited a distinct advantage
      of simple preparation, surface renewal, good reproducibility and good stability.

PMID- 18804642
TI  - Stacking and separation of urinary porphyrins in capillary electrophoresis:
      optimization of concentration efficiency and resolution.
AB  - We demonstrated that anionic porphyrins could be stacked and separated in
      micellar electrokinetic chromatography (MEKC) and microemulsion electrokinetic
      chromatography (MEEKC) by applying acetonitrile and high salt content in human
      urine sample matrix. The introduction of sample containing acetonitrile and
      sodium chloride into the CE capillary at more than 10% of the total capillary
      volume resulted in the improvement of peak resolution and the enhancement of
      detection sensitivity. The achieved acetonitrile stacking enrichment factors of
      six porphyrins ranged from 12 to 32 in MEKC and from 28 to 33 in MEEKC,
      respectively. The stacking technique was successfully applied for analyzing
      porphyrins present in urine samples that were deproteinized with acetonitrile.
      For the analysis of coproporphyrin isomers, addition of the sodium cholate (SC)
      into micelle and microemulsion solutions provided adequate resolution.
      Calibration curves obtained for the determination of coproporphyrin isomers were
      found linear between 30 and 400 nmol L(-1), and the limit of detection (LOD) was
      20 nmol L(-1) in MEEKC. Intra- and interday precisions (n=11) in the
      microemulsion separation system for the isomers at spiked concentrations of 40
      400 nmol L(-1) in urine were in the range of 0.1-0.4% and 0.7-7.6% for migration
      time and peak area, respectively. Coproporphyrin III, coproporphyrin I and
      uroporphyrin were detected at levels of 80.7 nmol L(-1), 32.3 nmol L(-1) and 19.8
      nmol L(-1), respectively, in the urine samples collected from healthy
      individuals. Different porphyrin profiles, however, were observed in urine
      samples from porphyria cutanea tarda (PCT) patients.

PMID- 18804643
TI  - Rate of phosphoantimonylmolybdenum blue complex formation in acidic persulfate
      digested sample matrix for total dissolved phosphorus determination: importance
      of post-digestion pH adjustment.
AB  - Acidic persulfate oxidation is one of the most common procedures used to digest
      dissolved organic phosphorus compounds in water samples for total dissolved
      phosphorus determination. It has been reported that the rates of
      phosphoantimonylmolybdenum blue complex formation were significantly reduced in
      the digested sample matrix. This study revealed that the intermediate products of
      persulfate oxidation, not the slight change in pH, cause the slowdown of color
      formation. This effect can be remedied by adjusting digested samples pH to a near
      neural to decompose the intermediate products. No disturbing effects of chlorine
      on the phosphoantimonylmolybdenum blue formation in seawater were observed. It is
      noted that the modification of mixed reagent recipe cannot provide near neutral
      pH for the decomposition of the intermediate products of persulfate oxidation.
      This study provides experimental evidence not only to support the recommendation
      made in APHA standard methods that the pH of the digested sample must be adjusted
      to within a narrow range of sample, but also to improve the understanding of role
      of residue from persulfate decomposition on the subsequent
      phosphoantimonylmolybdenum blue formation.

PMID- 18804644
TI  - Quick analysis of baicalin in Scutellariae Radix by enzyme-linked immunosorbent
      assay using a monoclonal antibody.
AB  - To establish an immunoassay for baicalin (BA), a hybridoma cell line (9D6)
      secreting a monoclonal antibody (MAb) against BA was prepared by cell fusion with
      splenocytes derived from a mouse immunized with BA-bovine serum albumin (BSA)
      conjugate and a myeloma cell line, SP2/0-Ag14. MAb 9D6 shows specific reactivity
      against BA and its aglycone, baicalein, but not against other natural products.
      We developed an enzyme-linked immunosorbent assay (ELISA) using MAb 9D6 in a
      competitive manner, ranging from 200 ng/mL to 2 microg/mL. After validating the
      developed ELISA on the basis of intra- and inter-assays and a recovery
      experiment, it was found that the ELISA was not only simple, but also
      sufficiently reliable and accurate for quality control of Scutellariae Radix. It
      allowed determination of BA in complex and mixed materials, such as Kampo
      medicines.

PMID- 18804645
TI  - Reversed-phase high performance liquid chromatography (RP-HPLC) characteristics
      of some 9,10-anthraquinone derivatives using binary acetonitrile-water mixtures
      as mobile phase.
AB  - The retention behavior of 28 synthesized 9,10-anthraquinone derivatives in a
      reversed-phase (RP) high performance liquid chromatography (HPLC) system has been
      studied on a C18-RP column using acetonitrile-water mixtures as mobile phase. The
      influences of the composition of mobile phase and the solute structure on the
      retention times of 9,10-anthraquinone derivatives were investigated by linear
      solvation free energy relationship (LSFER) and quantitative structure-retention
      relationship (QSRR) analyses. Among different solvatochromic parameters of
      solvent systems, their polarity/polarizability parameter (pi*) was identified as
      the controlling factor affecting retention behavior of these compounds. A four
      parametric QSRR model was obtained between solute structures and retention
      indices. Finally, a unified model containing both the molecular structure
      parameters and mobile phase properties was developed to describe the
      chromatographic behavior of the systems studied. The resulted QSRR models could
      explain and predict higher than 90% of variances in the retention indices. Among
      the solvent properties, polarity/polarizability parameter (pi*), and among the
      solute properties, HATS5v (leverage-weighted autocorrelation of lag 5/weighted by
      atomic van der Waals volumes, GETAWAY descriptors), Mor14p (3D-MoRSE-signal
      14/weighted by atomic polarizabilities, 3D-MoRSE descriptors), GATS5p (Geary
      autocorrelation-lag 5/weighted by atomic polarizabilities, 2D autocorrelations)
      and R6u+(R maximal autocorrelation of lag 6/unweighted, GETAWAY descriptors) were
      identified as controlling factors in the RP-HPLC behavior of 9,10-anthraquinone
      derivatives in actonitrile-water binary solvents.

PMID- 18804646
TI  - Quantitative Structure-Retention relationship study of the constituents of
      saffron aroma in SPME-GC-MS based on the projection pursuit regression method.
AB  - Quantitative Structure-Retention Relationship (QSRR) studies were performed for
      predicting the retention times of 43 constituents of saffron aroma, which were
      analyzed by solid-phase micro-extraction gas chromatography-mass spectrometry
      (SPME-GC-MS). The chemical descriptors were calculated from the molecular
      structures of the constituents of saffron aroma alone, and the linear and non
      linear QSRR models were constructed using the Best Multi-Linear Regression (BMLR)
      and Projection Pursuit Regression (PPR) methods. The predicted results of the two
      approaches were in agreement with the experimental data. The coefficients of
      determination (R(2)) of the linear BMLR model were 0.9434 and 0.8725 for the
      training and test sets, respectively. The other non-linear PPR model gave a more
      accurate prediction with R(2) values of 0.9806 (training set) and 0.9456 (test
      set). The proposed models could also identify and provide some insights into
      structural features that may play a role on the retention behaviors of the
      constituents of saffron aroma in the SPME-GC-MS system. This study affords a
      simple but efficient approach for studying the retention behaviors of other
      similar plants and herbs.

PMID- 18804647
TI  - Amperometric sulfite sensor based on multiwalled carbon nanotubes/ferrocene
      branched chitosan composites.
AB  - A novel amperometric sensor for the determination of sulfite was fabricated based
      on multiwalled carbon nanotubes (MWCNTs)/ferrocene-branched chitosan (CHIT-Fc)
      composites-covered glassy carbon electrode (GCE). The electrochemical behavior of
      the sensor was investigated in detail by cyclic voltammetry. The apparent surface
      electron transfer rate constant (K(s)) and charge transfer coefficient (alpha) of
      the CHIT-Fc/MWCNTs/GCE were also determined by cyclic voltammetry, which were
      about 1.93 cm s(-1) and 0.42, respectively. The sensor displayed good
      electrocatalytic activity towards the oxidation of sulfite. The peak potential
      for the oxidation of sulfite was lowered by at least 330 mV compared with that
      obtained at CHIT/MWCNTs/GCE. In optimal conditions, linear range spans the
      concentration of sulfite from 5 microM to 1.5mM and the detection limit was 2.8
      microM at a signal-to-noise ratio of 3. The proposed method was used for the
      determination of sulfite in boiler water. In addition, the sensor has good
      stability and reproducibility.

PMID- 18804648
TI  - Measurement of soil/dust arsenic by gas phase chemiluminescence.
AB  - A gas phase chemiluminescence (GPCL)-based method for trace measurement of
      arsenic has been recently described for the measurement of arsenic in water. The
      principle is based on the reduction of inorganic As to AsH(3) at a controlled pH
      (the choice of pH governs whether only As(III) or all inorganic As is converted)
      and the reaction of AsH(3) with O(3) to produce chemiluminescence (Idowu et al.,
      Anal. Chem. 78 (2006) 7088-7097). The same general principle has also been used
      in postcolumn reaction detection of As, where As species are separated
      chromatographically, then converted into inorganic As by passing through a UV
      photochemical reactor followed by AsH(3) generation and CL reaction with ozone
      (Idowu and Dasgupta, Anal. Chem. 79 (2007) 9197-9204). In the present paper we
      describe the measurement of As in different soil and dust samples by serial
      extraction with water, citric acid, sulfuric acid and nitric acid. We also
      compare parallel measurements for total As by induction coupled plasma mass
      spectrometry (ICP-MS). As(V) was the only species found in our samples. Because
      of chloride interference of isobaric ArCl(+) ICP-MS analyses could only be
      carried out by standard addition; these results were highly correlated with
      direct GPCL and LC-GPCL results (r(2)=0.9935 and 1.0000, respectively). The limit
      of detection (LOD) in the extracts was 0.36 microg/L by direct GPCL compared to
      0.1 microg/L by ICP-MS. In sulfuric acid-based extracts, the LC-GPCL method
      provided LODs inferior to those previously observed for water-based standards and
      were 2.6, 1.3, 6.7, and 6.4 microg/L for As(III), As(V), dimethylarsinic acid
      (DMA) and monomethylarsonic acid (MMA), respectively.

PMID- 18804649
TI  - The effects of grinding methods on metals concentrations in soil.
AB  - Multi-increment sampling (MIS) has been most extensively used for munitions
      constituents at environmental sites where a high degree of contaminant
      heterogeneity exits. A revised method (USEPA Method 8330B) for explosives that
      uses MIS was announced in the fall of 2006, but similar guidance has not been
      reported for testing metals in soils. Questions have been raised as how to
      prepare representative analytical samples for metals determination from field
      composites. Three different grinding procedures were used in this study for three
      soil types to determine if grinding (relative to homogenizing soil without
      grinding) increases metal concentrations and decreases variability. The
      performance of these procedures was demonstrated via the analysis of replicates
      (n=16 for two soil types) using statistical evaluations that included
      calculations of various descriptive statistics (e.g., medians, means and standard
      deviations), Kruskal-Wallis (KW) tests for the medians and two tests for the
      variances (Bartlett's and Levene's test). There was a slight increase in
      concentrations for several of the metals in the clay loam soil after grinding,
      although the increases were a small percentage of the concentrations measured.
      The standard deviations (and variances) for replicate digestions and analyses
      generally decreased, although anomalies were observed. The grinding methods
      increased precision overall, however, the data indicated that the roller mill
      grinding was not as effective as the other grinding methods tested.

PMID- 18804650
TI  - Development of a new sequential injection in-line cloud point extraction system
      for flame atomic absorption spectrometric determination of manganese in food
      samples.
AB  - A preconcentration method for manganese determination by sequential injection
      cloud point extraction with subsequent detection by flame atomic absorption
      spectrometry (FAAS) has been developed. The enrichment of Mn was performed after
      a preliminary on-line cloud point extraction and entrapment of manganese
      containing surfactant aggregated within a minicolumn packed with cotton. The
      laboratory-made reagent 4-(5'-bromo-2'-thiazolylazo)orcinol (Br-TAO) and the
      surfactant Triton X-114 were used for cloud point extraction. The manganese ions
      were eluted with sulphuric acid solution and directly introduced into the FAAS.
      Chemical and flow variables affecting the preconcentration were studied. Using a
      sample volume of 2.80 mL the limit of detection and enrichment factor were
      calculated to be 0.5 microg L(-1) and 14, respectively. The sample frequency is
      48 h(-1), considering a total run cycle of 75 s. The accuracy of the proposed
      method has been demonstrated by the analysis of the certified reference
      biological materials rice flour and tomato leaves. The method has been applied to
      determination of manganese in food samples.

PMID- 18804651
TI  - Determination of chlorogenic acid in coffee using a biomimetic sensor based on a
      new tetranuclear copper(II) complex.
AB  - A new tetranuclear copper(II) complex which mimics the active site of catechol
      oxidase was synthesized and characterized by IR, CHN, electronic spectroscopic
      and (1)H NMR methods. The title complex [Cu(2)(mu-OH)(bpbpmp
      NO(2))](2)[ClO(4)](2) was employed in the construction of a novel biomimetic
      sensor and used in the determination of chlorogenic acid by square wave
      voltammetry. The performance and optimization of the resulting biomimetic sensor
      were studied in detail. The best response of this sensor was obtained for
      75:15:10% (w/w/w) ratio of the graphite powder:nujol:Cu(II) complex, 0.1 mol L(
      1) phosphate buffer solution (pH 7.0), with frequency, pulse amplitude, and scan
      increment at 30 Hz, 100 mV, and 3.0 mV, respectively. The chlorogenic acid
      concentration was linear in the range of 5.0x10(-6) to 1.45x10(-4)mol L(-1)
      (r=0.9985) with a detection limit of 8.0x10(-7)mol L(-1). This biomimetic sensor
      demonstrated long-term stability (250 days; 640 determinations) and
      reproducibility, with a relative standard deviation of 10.0%. The recovery study
      of chlorogenic acid in coffee samples gave values from 93.2% to 106.1% and the
      concentrations determined showed good agreement when compared with those obtained
      using capillary electrophoresis at the 95% confidence level.

PMID- 18804652
TI  - Comparison of direct solid sampling and slurry sampling for the determination of
      cadmium in wheat flour by electrothermal atomic absorption spectrometry.
AB  - Two analytical methods for the determination of cadmium in wheat flour by
      electrothermal atomic absorption spectrometry without prior sample digestion have
      been compared: direct solid sampling analysis (SS) and slurry sampling (SlS).
      Besides the conventional modifier mixture of palladium and magnesium nitrates (10
      microg Pd+3 microg Mg), 0.05% (v/v) Triton X-100 has been added to improve the
      penetration of the modifier solution into the solid sample, and 0.1% H(2)O(2) in
      order to promote an in situ digestion for SS. For SlS, 30 microg Pd, 12 microg Mg
      and 0.05% (v/v) Triton X-100 have been used as the modifier mixture. Under these
      conditions, and using a pyrolysis temperature of 800 degrees C, essentially no
      background absorption was observed with an atomization temperature of 1600
      degrees C. About 2 mg of sample have been typically used for SS, although as much
      as 3-5 mg could have been introduced. In the case of SlS multiple injections had
      to be used to achieve the sensitivity required for this determination.
      Calibration against aqueous standards was feasible for both methods. The
      characteristic mass obtained with SS was 0.6 pg, and that with SlS was 1.0 pg.
      The limits of detection were 0.4 and 0.7 ng g(-1), the limits of quantification
      were 1.3 and 2.3 ng g(-1) and the relative standard deviation (n=5) was 6-16% and
      9-23% for SS and SlS, respectively. The accuracy was confirmed by the analysis of
      certified reference materials. The two methods were applied for the determination
      of cadmium in six wheat flour samples acquired in supermarkets of different
      Brazilian cities. The cadmium content varied between 8.9+/-0.5 and 13+/-2 ng g(
      1) (n=5). Direct SS gave results similar to those obtained with SlS using multi
      injections; the values of both techniques showed no statistically significant
      difference at the 95% confidence level. Direct SS was finally adopted as the
      method of choice, due to its greater simplicity, the faster speed of analysis and
      the better figures of merit.

PMID- 18804653
TI  - Extraction and high performance liquid chromatographic determination of 3-indole
      butyric acid in pea plants by using imidazolium-based ionic liquids as
      extractant.
AB  - In this paper, imidazolium-based ionic liquids [C(4)mim][PF(6)],
      [C(6)mim][PF(6)], [C(8)mim][PF(6)], [C(6)mim][BF(4)] and [C(8)mim][BF(4)] were
      tested as extracting solvents for removal of 3-indole butyric acid (IBA) from
      aqueous media with subsequent determination using HPLC. Percent extraction of IBA
      was strongly affected by pH of aqueous phases and the chemical structures of
      ionic liquids (ILs). Extraction of IBA was quantitative in the pH values lower
      than pK(a) of IBA. Considering both extraction and stripping efficiencies of IBA,
      [C(4)mim][PF(6)] was found to act more efficient than other studied ILs. Capacity
      of [C(4)mim][PF(6)] was 17.6x10(-4)mmol IBA per 1.0 mL of IL. Ionic strength of
      aqueous phase and temperature had shown no serious effects on extraction
      efficiency of IBA. A preconcentration factor of 100 and a relative standard
      deviation of 1.16% were obtained. It was found that ionic liquid phase was
      reusable almost five times for extraction/stripping purposes. 3-Indole acetic
      acid showed interferential effect in the extraction step. In order to assess the
      applicability of the method, extraction and stripping of IBA from pea plants and
      some other samples were studied.

PMID- 18804654
TI  - Validated hydrophilic interaction LC-MS/MS method for simultaneous quantification
      of dacarbazine and 5-amino-4-imidazole-carboxamide in human plasma.
AB  - A hydrophilic interaction high performance liquid chromatography-tandem mass
      spectrometric method has been developed and validated for simultaneous
      quantification of dacarbazine (DTIC) and its terminal metabolite, 5-amino-4
      imidazole-carboxamide (AIC) in human plasma. The plasma samples are first
      extracted by a C8+SCX mixed-mode 96-well plate to extend the extraction stability
      of DTIC and AIC. The extracted residues are further cleaned by a primary and
      secondary amine (PSA) adsorbent for minimization of matrix effect. Analyses are
      done on an Amide-80 HPLC column coupled to a tandem mass spectrometer fitted with
      an atmospheric pressure turbo ion spray ionization interface in the positive-ion
      mode. Both DTIC and AIC have reproducible retention times on the Amide-80 HPLC
      column. This type of column not only has an excellent column life (over 4000
      injections), but also has zero carryover effect. The injection volume should be
      limited at 10 microL or less to avoid the peak splitting. The validated
      concentration ranges are from 0.5 to 500 ng/mL for DTIC and from 2.0 to 500 ng/mL
      for AIC. The validated method has been successfully applied to determine the
      pharmacokinetic profiles for human patients receiving DTIC infusions.

PMID- 18804655
TI  - Direct determination of uranium in seawater by laser fluorimetry.
AB  - A method for estimation of uranium in seawater by using steady state laser
      flourimetry is described. Uranium present in seawater, in concentration of
      approximately 3 ng ml(-1) was estimated without prior separation of matrix.
      Quenching effect of major ions (Cl(-), Na(+), SO(4)(-), Mg(+), Ca(+), K(+),
      HCO(3)(-), Br(-)) present in seawater on fluorescence intensity of uranium was
      studied. The concentration of phosphoric acid required for maximum enhancement of
      fluorescence intensity was optimized and was found to be 5%. Similarly the volume
      of concentrated nitric acid required to eliminate the quenching effect of
      chloride and bromide completely from 5 ml of seawater were optimized and was
      found to be 3 ml. A simple equation was derived using steady state fluorescence
      correction method and was used for calculation of uranium concentration in
      seawater samples. The method has a precesion of 1% (1s, n=3). The values obtained
      from laser fluorimetry were validated by analyzing the same samples by linear
      sweep adsorptive stripping voltametry (LSASV) of the uranium-chloranilic acid
      (2,5-dichloro-3,6-dihydroxy-1,4-benzoquinone) complex. Both the values are well
      in agreement.

PMID- 18804656
TI  - The extraction and speciation of arsenic in rice flour by HPLC-ICP-MS.
AB  - Several solvent mixtures and techniques for the extraction of arsenic (As)
      species from rice flour samples prior to their analysis by HPLC-ICP-MS were
      investigated. Microwave-assisted extraction using water at 80 degrees C for 30
      min provided the highest extraction efficiency. Total recoveries of extracted As
      species were in good agreement with the total As concentrations determined by ICP
      MS after microwave-assisted acid digestion of the samples. Arsenite [As(III)],
      arsenate [As(V)] and dimethylarsinic acid (DMAA) were the main species detected
      in rice flour samples.

PMID- 18804657
TI  - NMR metabolic profiling of organic and aqueous sea bass extracts: implications in
      the discrimination of wild and cultured sea bass.
AB  - The nuclear magnetic resonance (NMR) technique was used as analytical tool to
      determine the complete metabolic profiling of sea bass extracts: water-soluble
      metabolites belonging to different classes such as sugars, amino acids,
      dipeptides and organic acids as well as metabolites soluble in organic solvent
      such as lipids, sterols and fatty acids were identified. The metabolite profiling
      together with a suitable statistical analysis were used to discriminate between
      wild and cultured sea bass samples. Preliminary results show that discrimination
      between wild and cultured sea bass was obtained not only using fatty acid
      composition but also cholesterol and phosphatidylethanolamine and some water
      soluble metabolites such as choline, trimethylamine oxide, glutamine, fumaric and
      malic acids.

PMID- 18804658
TI  - Relevance of NH4F in acid digestion before ICP-MS analysis.
AB  - In order to implement a simpler, less expensive and more safe sample dissolution
      procedure, we have substituted the HF-HClO(4) mixture by NH(4)F. By testing three
      certified reference materials, lichen 336, basalt BE-N, soil 7, it was found that
      the three-reagents digestion without HF and HClO(4) (HNO(3)+H(2)O(2)+NH(4)F was
      used) was very effective for the pretreatment of ICP-MS measurement. The
      comparison was based on the measurement results and their uncertainties. All are
      reference material for amount contents of different trace elements. The accuracy
      and precision of the developed method were tested by replicate analyses of
      reference samples of established element contents. The accuracy of the data as
      well as detection limits (LODs) vary among elements but are usually very good
      (accuracy better than 8%, LODs usually below 1 microg/g in solids). ICP-MS
      capabilities enable us to determine routinely 13 and 16 minor and trace elements
      in basalt and soil.

PMID- 18804659
TI  - Improvement of acetylcholinesterase-based assay for organophosphates in way of
      identification by reactivators.
AB  - Organophosphates present serious fulmination in several aspects of human life.
      Detection of organophosphates is frequently based on following
      acetylcholinesterase (AChE) inhibition. Although limit of detection and
      sensitivity for AChE-based assays seem to be intriguing, the identification of
      organophosphates is not currently efficient in this way. We introduce an
      improvement of AChE-based assay by reactivators using a selective come-back of
      AChE activity after previous inhibition. We have chosen four organophosphates:
      paraoxon-ethyl, paraoxon-methyl, trichlorfon, methamidophos as representative
      pesticides and the three most available reactivators: HI-6, obidoxime,
      pralidoxime. Reactivation was realized in the 96-wells photometric microplates
      and activity of human recombinant AChE was followed by reaction of Ellman's
      reagent with one of enzyme digestion product: thiocholine. Distinguishing of
      reactivation efficacy was judged by the independent two population t-test. The
      most significant identification was based on methamidophos inhibited AChE
      reactivation by HI-6 or pralidoxime and paraoxon-ethyl inhibited AChE by
      obidoxime; moreover, identification of trichlorfon and paraoxon-methyl was
      possible, too. Practical impact of described method is discussed.

PMID- 18804660
TI  - A novel amperometric biosensor based on NiO hollow nanospheres for biosensing
      glucose.
AB  - NiO hollow nanospheres were synthesized by controlled precipitation of metal ions
      with urea using carbon microspheres as templates, which were for the first time
      adopted to construct a novel amperometric glucose biosensor. Glucose oxidase was
      immobilized on the surface of hollow nanospheres through chitosan-assisted cross
      linking technique. Due to the high specific active sites and high
      electrocatalytic activity of NiO hollow nanospheres, the constructed glucose
      biosensors exhibited a high sensitivity of 3.43 microA/mM. The low detection
      limit was estimated to be 47 microM (S/N=3), and the Michaelis-Menten constant
      was found to be 7.76 mM, indicating the high affinity of enzyme on NiO hollow
      nanospheres to glucose. These results show that the NiO hollow nanospheres are a
      promising material to construct enzyme biosensors.

PMID- 18804661
TI  - Clinical neurology and its basic science underpinning. Preface.

PMID- 18804662
TI  - Clinical neurology and stroke. Foreword.

PMID- 18804663
TI  - Topographic classification of ischemic stroke.

PMID- 18804664
TI  - Identification, risks, and treatment of transient ischemic attack.

PMID- 18804665
TI  - Medical complications of stroke.

PMID- 18804666
TI  - Anterior circulation syndromes.

PMID- 18804667
TI  - Posterior circulation strokes.

PMID- 18804668
TI  - Lacunes and lacunar syndromes.

PMID- 18804669
TI  - Hemorrhagic stroke syndromes: clinical manifestations of intracerebral and
      subarachnoid hemorrhage.

PMID- 18804670
TI  - Eye syndromes and the neuro-ophthalmology of stroke.

PMID- 18804671
TI  - Post-stroke seizures.

PMID- 18804672
TI  - Stroke-related psychiatric disorders.

PMID- 18804673
TI  - Vascular dementia.

PMID- 18804674
TI  - "Silent" cerebral infarcts and microbleeds.

PMID- 18804675
TI  - Spinal strokes.

PMID- 18804676
TI  - Extracranial and intracranial atheroma, and artery-to-artery embolism.

PMID- 18804677
TI  - Cardio-embolic stroke.

PMID- 18804678
TI  - Cervical artery dissections.

PMID- 18804679
TI  - Intracerebral hemorrhage.

PMID- 18804680
TI  - Subarachnoid hemorrhage.

PMID- 18804681
TI  - Cerebral venous thrombosis.

PMID- 18804682
TI  - Illicit drug use/abuse and stroke.

PMID- 18804683
TI  - Stroke, migraine, and headache.

PMID- 18804684
TI  - Infections and stroke.

PMID- 18804685
TI  - Vasculitis and stroke.

PMID- 18804686
TI  - Hematological diseases and stroke.

PMID- 18804687
TI  - Stroke related to systemic illness and complicated surgery.

PMID- 18804688
TI  - Rare causes of stroke.

PMID- 18804689
TI  - Folic acid and folates. Preface.

PMID- 18804690
TI  - Folate-mediated one-carbon metabolism.
AB  - Tetrahydrofolate (THF) polyglutamates are a family of cofactors that carry and
      chemically activate one-carbon units for biosynthesis. THF-mediated one-carbon
      metabolism is a metabolic network of interdependent biosynthetic pathways that is
      compartmentalized in the cytoplasm, mitochondria, and nucleus. One-carbon
      metabolism in the cytoplasm is required for the synthesis of purines and
      thymidylate and the remethylation of homocysteine to methionine. One-carbon
      metabolism in the mitochondria is required for the synthesis of formylated
      methionyl-tRNA; the catabolism of choline, purines, and histidine; and the
      interconversion of serine and glycine. Mitochondria are also the primary source
      of one-carbon units for cytoplasmic metabolism. Increasing evidence indicates
      that folate-dependent de novo thymidylate biosynthesis occurs in the nucleus of
      certain cell types. Disruption of folate-mediated one-carbon metabolism is
      associated with many pathologies and developmental anomalies, yet the biochemical
      mechanisms and causal metabolic pathways responsible for the initiation and/or
      progression of folate-associated pathologies have yet to be established. This
      chapter focuses on our current understanding of mammalian folate-mediated one
      carbon metabolism, its cellular compartmentation, and knowledge gaps that limit
      our understanding of one-carbon metabolism and its regulation.

PMID- 18804691
TI  - Mathematical models of folate-mediated one-carbon metabolism.
AB  - Folate-mediated one-carbon metabolism is an unusually complex metabolic network,
      consisting of several interlocking cycles, and compartmentation between cytosol
      and mitochondria. The cycles have diverse functions, the primary being
      thymidylate synthesis (the rate limiting step in DNA synthesis), the initial
      steps in purine synthesis, glutathione synthesis, and a host of methyl transfer
      reactions that include DNA and histone methylation. Regulation within the network
      is accomplished by numerous allosteric interactions in which metabolites in one
      part of the network affect the activity of enzymes elsewhere in the network.
      Although a large body of experimental work has elucidated the details of the
      mechanisms in every part of the network, the multitude of complex and non-linear
      interactions within the network makes it difficult to deduce how the network as a
      whole operates. Understanding the operation of this network is further
      complicated by the fact that human populations maintain functional polymorphisms
      for several enzymes in the network, and that the network is subject to continual
      short and long-term fluctuations in its inputs as well as in demands on its
      various outputs. Understanding how such a complex system operates is possible
      only by means of mathematical models that take account of all the reactions and
      interactions. Simulations with such models can be used as an adjunct to
      laboratory experimentation to test ideas and alternative hypotheses and
      interpretations quickly and inexpensively. A number of mathematical models have
      been developed over the years, largely motivated by the need to understand the
      complex mechanisms by which anticancer drugs like methotrexate inhibit nucleotide
      synthesis and thus limit the ability of cells to divide. More recently,
      mathematical models have been used to investigate the regulatory and homeostatic
      mechanisms that allow the system to accommodate large fluctuations in one part of
      the network without affecting critical functions elsewhere in the network.

PMID- 18804692
TI  - Folate deprivation, the methionine cycle, and Alzheimer's disease.
AB  - Folate deficiency is associated with increase in homocysteine levels. Abnormal
      plasma levels of that neurotoxic nonproteinogenic amino acid is implicated in
      many pathological conditions including cardiovascular diseases, neural tube
      defects, and is now recognized as a risk factor in Alzheimer's disease (AD)
      dementia. Homocysteine elimination is regulated by two metabolic pathways,
      namely, the transmethylation and the transsulfuration pathways. Its elimination
      via these two metabolic pathways is modulated by folate, a member of the B
      vitamin family. Folate provides, via its metabolic end product 5
      methyltetrahydrofolate, a methyl group that is used to reconvert homocysteine
      back to methionine through the transmethylation pathway. The efficiency of folate
      metabolism has an impact on the availability of S-adenosylmethionine, a compound
      that is known to activate homocysteine flux through the transsulfuration pathway
      and is necessary for utilization of a downstream antioxidant called glutathione
      under the catalysis of glutathione S-transferase enzyme. In this review, we will
      explore the impact of folate deprivation on the regulation of the methionine
      cycle and exhaustively describe different biochemical reactions that are
      implicated in the regulation of homocysteine elimination and that folate
      deficiency influences in AD neuropathology.

PMID- 18804693
TI  - Molecular mechanisms of adaptation to folate deficiency.
AB  - Folic acid is an essential vitamin for a wide spectrum of biochemical reactions;
      however, unlike bacteria and plants, mammals are devoid of folate biosynthesis
      and thus must obtain this cofactor from exogenous sources. Therefore, folate
      deficiency may impair the de novo biosynthesis of purines and thymidylate and
      thereby disrupt DNA and RNA metabolism, homocysteine remethylation, methionine
      biosynthesis, and subsequent formation of S-adenosylmethionine (the universal
      methyl donor) which in turn may lead to altered methylation reactions. This
      impaired folate-dependent intracellular metabolism can lead to several key
      pathologies including, for example, megaloblastic anemia, homocysteinemia,
      cardiovascular disease, embryonic defects, in particular neural tube defects
      (NTDs), congenital heart defects, and possibly cancer. The current review
      presents and evaluates the up-to-date knowledge regarding the molecular
      mechanisms underlying cellular survival and/or adaptation to folate deficiency or
      insufficiency. These mechanisms of adaptation to folate deficiency generally
      associated with folate uptake, intracellular folate retention, folate-dependent
      metabolism, and active folate efflux specifically include: (a) Up- or
      downregulation of various folate-dependent enzymes like dihydrofolate reductase
      (DHFR) and thymidylate synthase (TS), (b) Cellular retention of folates via
      polyglutamylation by the enzyme folylpoly-gamma-glutamate synthetase (FPGS), (c)
      Overexpression of folate influx systems including the reduced folate carrier
      (RFC), folate receptor (FR) as well as the proton-coupled folate transporter
      (PCFT), a recently identified intestinal folate influx transporter optimally
      functioning at the acidic microclimate of the upper intestinal epithelium, (d)
      Downregulation of ATP-driven folate efflux transporters of the multidrug
      resistance protein (MRP; ABCC) family and breast cancer resistance protein (BCRP;
      ABCG2) that belong to the multidrug resistance (MDR) efflux transporters of the
      ATP-binding cassette (ABC) superfamily. Moreover, the intricate interplay between
      various components of the adaptive response to folate deprivation is also
      discussed.

PMID- 18804695
TI  - Renal conservation of folates role of folate transport proteins.
AB  - Folates play vital roles in one-carbon metabolism that produces the early
      substrates necessary for nucleotide synthesis and salvage. Folates are essential
      vitamins in that humans cannot synthesize them and are totally dependent on the
      diet to obtain them. As water-soluble vitamins, they would be easily filtered by
      the kidney and lost to the tubular fluid but for a highly efficient renal
      conservation mechanism. This renal "folate trap" is made up of alpha-folate
      receptors and reduced folate carriers. The locations of these transporters are
      such that they direct folate transport from the apical/luminal sides of kidney
      cells to the basolateral/plasma sides. In addition, other transporters such as
      organic anion transporters and multidrug resistance proteins are also found in
      kidney cells and play a role in renal elimination of folate analogues such as
      antifolate cancer chemotherapy drugs. This chapter discusses how these
      transporter activities manifest themselves in folate and antifolate
      pharmacokinetics. It also discusses effects of alcohol on renal reabsorption of
      folates.

PMID- 18804694
TI  - Structure and function of the reduced folate carrier a paradigm of a major
      facilitator superfamily mammalian nutrient transporter.
AB  - Folates are essential for life and folate deficiency contributes to a host of
      health problems including cardiovascular disease, fetal abnormalities,
      neurological disorders, and cancer. Antifolates, represented by methotrexate,
      continue to occupy a unique niche among the modern day pharmacopoeia for cancer
      along with other pathological conditions. This article focuses on the biology of
      the membrane transport system termed the "reduced folate carrier" or RFC with a
      particular emphasis on RFC structure and function. The ubiquitously expressed RFC
      is the major transporter for folates in mammalian cells and tissues. Loss of RFC
      expression or function portends potentially profound physiological or
      developmental consequences. For chemotherapeutic antifolates used for cancer,
      loss of RFC expression or synthesis of mutant RFC protein with impaired function
      results in antifolate resistance due to incomplete inhibition of cellular enzyme
      targets and low levels of substrate for polyglutamate synthesis. The functional
      properties for RFC were first documented nearly 40 years ago in murine leukemia
      cells. Since 1994, when RFC was first cloned, tremendous advances in the
      molecular biology of RFC and biochemical approaches for studying the structure of
      polytopic membrane proteins have led to an increasingly detailed picture of the
      molecular structure of the carrier, including its membrane topology, its N
      glycosylation, identification of functionally and structurally important domains
      and amino acids, and helix packing associations. Although no crystal structure
      for RFC is yet available, biochemical and molecular studies, combined with
      homology modeling, based on homologous bacterial major facilitator superfamily
      transporters such as LacY, now permit the development of experimentally testable
      hypotheses designed to establish RFC structure and mechanism.

PMID- 18804696
TI  - Exploitation of the folate receptor in the management of cancer and inflammatory
      disease.
AB  - Over the last 25+ years, the folate receptor (FR) has emerged as an attractive
      tumor biomarker with the potential to be exploited for therapeutic purposes.
      Increasing evidence suggests that this endocytosing protein can functionally
      mediate the cellular uptake and retention of natural folates, certain
      antifolates, and folate-drug conjugates; the consequences of the latter two
      events could result in biological modulation, including (but not limited to)
      tumor-targeted cytotoxicity. Because its tissue expression profile appears to be
      somewhat limited to either tissues responsible for whole body retention of
      folates (e.g., kidney and placenta), or certain pathologic tissues (e.g., tumors
      or activated macrophages), the FR is believed to be a useful biological target
      for disease management. Indeed, recent years have been peppered with reports of
      novel FR-targeted therapies, and many have demonstrated impressive in vivo
      potency, particularly against tumor xenografts, without the undesirable toxicity
      that often accompanies nontargeted drug regimens. This chapter will provide
      essential details on the properties of the FR, including where it is expressed
      and how it has been successfully manipulated for therapeutic benefit.

PMID- 18804697
TI  - Folate receptor expression in pituitary adenomas cellular and molecular analysis.
AB  - Clinically nonfunctional pituitary adenomas cause hypopituitarism or compression
      of regional structures. Unlike functional tumors, there is no available medical
      treatment or specific imaging technique for these tumors. We have recently
      discovered that both folate receptor (FR)alpha mRNA and protein are uniquely
      overexpressed in nonfunctional pituitary tumors, but not in functional adenomas.
      We hypothesized that FRalpha may hold significant promise for medical treatment
      by enabling novel molecular imaging and targeted therapy. Here, we used murine
      pituitary tumor cell line alphaT3-1 as a model to investigate the biological
      significance of FRalpha and its mutant FR67. We demonstrate that overexpression
      of FR facilitated tumor cell growth and anchorage-independent growth in soft
      agar. More colonies were observed in FR overexpressing cells than in mutant FR67
      clones in soft agar. Cell proliferation rate was increased, the percentage of
      cells in S-phase was increased, and high PCNA staining was detected in cells
      overexpressing the receptor. In alphaT3-1 cells transfected with mutant FR67,
      cell proliferation rate was reduced, the percentage of cells residing in S-phase
      was slightly decreased, and low PCNA staining was observed. By real-time
      quantitative PCR, the genes involved in NOTCH3 pathway including NOTCH3, HES-1,
      and TLE2 were altered; the mRNA expression of FGFR1 was upregulated, and ERbeta
      mRNA was downregulated in FR overexpressing cells. Our findings suggest that
      FRalpha plays a role in pituitary tumor formation, and this effect may in part be
      due to its regulation of the NOTCH3 pathway.

PMID- 18804698
TI  - Regulation of human dihydrofolate reductase activity and expression.
AB  - Dihydrofolate reductase (DHFR) enzyme catalyzes tetrahydrofolate regeneration by
      reduction of dihydrofolate using NADPH as a cofactor. Tetrahydrofolate and its
      one carbon adducts are required for de novo synthesis of purines and thymidylate,
      as well as glycine, methionine and serine. DHFR inhibition causes disruption of
      purine and thymidylate biosynthesis and DNA replication, leading to cell death.
      Therefore, DHFR has been an attractive target for chemotherapy of many diseases
      including cancer. Over the following years, in order to develop better
      antifolates, a detailed understanding of DHFR at every level has been undertaken
      such as structure-functional analysis, mechanisms of action, transcriptional and
      translation regulation of DHFR using a wide range of technologies. Because of
      this wealth of information created, DHFR has been used extensively as a model
      system for enzyme catalysis, investigating the relations between structure in
      silico structure-based drug design, transcription from TATA-less promoters,
      regulation of transcription through the cell cycle, and translational
      autoregulation. In this review, the current understanding of human DHFR in terms
      of structure, function and regulation is summarized.

PMID- 18804700
TI  - Methyltetrahydrofolate in folate-binding protein glycine N-methyltransferase.
AB  - In mammals, folate is used as a carrier of one-carbon units (C(1)) in nucleic
      acids metabolism and biological methylation. Among all forms of folate the most
      abundant is 5-methyltetrahydrofolate (5-CH(3)-THF), which is of exceptional
      importance. Its distinctive role among other forms of folate is in its dual
      function. As a C(1) carrier it is used for synthesis of methionine by
      remethylation of homocysteine. In addition, 5-CH(3)-THF is bound to and inhibits
      glycine-N-methyltransferase (GNMT). GNMT is one of the key enzymes in methionine
      and S-adenosylmethionine (AdoMet) metabolism. It removes excess AdoMet by using
      it for methylation of glycine. The interaction of 5-CH(3)-THF and GNMT was
      proposed as an important regulatory mechanism in AdoMet metabolism and biological
      methylation. The recent discovery of human individuals with mutant GNMT and the
      study of a mouse model with the GNMT gene knocked out showed that inactivation of
      that enzyme, indeed, has a significant impact on AdoMet levels in the liver and
      plasma. The crystal structure of GNMT complexed with 5-CH(3)-THF revealed that
      there are two folate molecules bound to one tetrameric form of GNMT, which is a
      basis for establishing of mechanism of inhibition of GNMT. The role of GNMT as a
      folate-binding protein and how it affects one-carbon folate metabolism is
      discussed.

PMID- 18804699
TI  - Catalysis of methyl group transfers involving tetrahydrofolate and B(12).
AB  - This review focuses on the reaction mechanism of enzymes that use B(12) and
      tetrahydrofolate (THF) to catalyze methyl group transfers. It also covers the
      related reactions that use B(12) and tetrahydromethanopterin (THMPT), which is a
      THF analog used by archaea. In the past decade, our understanding of the
      mechanisms of these enzymes has increased greatly because the crystal structures
      for three classes of B(12)-dependent methyltransferases have become available and
      because biophysical and kinetic studies have elucidated the intermediates
      involved in catalysis. These steps include binding of the cofactors and
      substrates, activation of the methyl donors and acceptors, the methyl transfer
      reaction itself, and product dissociation. Activation of the methyl donor in one
      class of methyltransferases is achieved by an unexpected proton transfer
      mechanism. The cobalt (Co) ion within the B(12) macrocycle must be in the Co(I)
      oxidation state to serve as a nucleophile in the methyl transfer reaction. Recent
      studies have uncovered important principles that control how this highly reducing
      active state of B(12) is generated and maintained.

PMID- 18804701
TI  - Mechanism-based inhibitors of folylpoly-gamma-glutamate synthetase and gamma
      glutamyl hydrolase: control of folylpoly-gamma-glutamate homeostasis as a drug
      target.
AB  - Intracellular folate pools consist primarily of gamma-glutamyl isopeptide
      conjugates of reduced forms of the vitamin, folic acid. Biosynthesis of these
      oligomeric isopeptides is catalyzed by the enzyme folylpoly-gamma-glutamate
      synthetase (FPGS). The highly anionic character of the oligomers renders them
      unable to cross the cell membrane and, therefore, these forms of reduced folates
      (and certain antifolates) accumulate in cells to high concentration. gamma
      Glutamyl hydrolase (GH) catalyzes the hydrolysis of the oligo-gamma-glutamates
      derivatives to monoglutamyl forms, which are substrates for the reduced folate
      carrier and able to exit the cell. This chapter describes research, primarily
      from our laboratories, on the design, synthesis, and biochemical evaluation of
      several novel analogues of glutamic acid, gamma-glutamyl peptides, and
      derivatives of folic acid as well as of antifolate drugs. These include a series
      of fluoroglutamic acids, fluoroglutamate-containing isopeptides, phosphorus
      containing pseudopeptides, and epoxide-containing peptidomimetics. The
      fluoroglutamic acids and fluoroglutamate-containing folates and antifolates
      exhibit position-dependent effects on the reactions catalyzed by FPGS and GH,
      thus providing insight into the catalytic mechanism and control of these enzymes.
      The phosphinic acid-containing pseudopeptides are the most potent inhibitors of
      FPGS identified to date, and were designed based on mechanistic enzymology data
      from our laboratories and others, prior to the publication of any structural
      information about the targeted enzymes.

PMID- 18804702
TI  - Methylenetetrahydrofolate reductase, common polymorphisms, and relation to
      disease.
AB  - Folate plays a key role in maintaining genomic stability and providing methyl
      groups for the formation of dTMP from dUMP which is required for DNA synthesis
      and repair and for the maintenance of methylation patterns involving cytosine or
      specific sites such as CpG islands. Under conditions of low folate, dUMP
      accumulates producing DNA strand breaks and micronucleus formation as a result of
      excessive uracil incorporation into DNA in place of thymine.
      Methylenetetrahydrofolate reductase (MTHFR) is an important folate metabolizing
      enzyme that catalyzes the irreversible conversion of 5,10
      methylenetretrahydrofolate, which is the methyl donor for the conversion of dUMP
      to dTMP, into 5-methyltetrahydrofolate, which is the methyl donor for
      remethylation of homocysteine to methionine. Certain common polymorphisms within
      the MTHFR gene (C677T, A1298C) result in reduced enzymatic activity and have been
      associated with reduced risk for a variety of cancers such as acute lymphocytic
      leukemia, lung and colorectal cancer. These common polymorphisms are also
      associated with hyperhomocysteinemia that has been reported to be an increased
      risk factor for neural tube defects and cardiovascular disease. In this chapter,
      we consider the role that MTHFR plays in relation to folate metabolism and the
      possible contribution made in relation to certain important clinical outcomes.

PMID- 18804703
TI  - Mitochondrial methylenetetrahydrofolate dehydrogenase, methenyltetrahydrofolate
      cyclohydrolase, and formyltetrahydrofolate synthetases.
AB  - Folate-mediated metabolism involves enzyme-catalyzed reactions that occur in the
      cytoplasmic, mitochondrial, and nuclear compartments in mammalian cells. Which of
      the folate-dependent enzymes are expressed in these compartments depends on the
      stage of development, cell type, cell cycle, and whether or not the cell is
      transformed. Mitochondria become formate-generating organelles in cells and
      tissues expressing the MTHFD2 and MTHFD1L genes. The products of these nuclear
      genes were derived from trifunctional precursor proteins, expressing
      methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase,
      and formyltetrahydrofolate synthetase activities. The MTHFD2 protein is a
      bifunctional protein with dehydrogenase and cyclohydrolase activities that arose
      from a trifunctional precursor through the loss of the synthetase domain and a
      novel adaptation to NAD rather than NADP specificity for the dehydrogenase. The
      MTHFD1L protein retains the size of its trifunctional precursor, but through the
      mutation of critical residues, both the dehydrogenase and cyclohydrolase
      activities have been silenced. MTHFD1L is thus a monofunctional
      formyltetrahydrofolate synthetase. This review discusses the properties and
      functions of these mitochondrial proteins and their role in supporting cytosolic
      purine synthesis during embryonic development and in cells undergoing rapid
      growth.

PMID- 18804704
TI  - The structure and mechanism of 6-hydroxymethyl-7,8-dihydropterin
      pyrophosphokinase.
AB  - 6-Hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK) catalyses the transfer
      of pyrophosphate from ATP to 6-hydroxymethyl-7,8-dihydropterin (HMDP), and is an
      essential enzyme in the biosynthesis of folic acid. It is also a potential target
      for antimicrobial drugs. HPPK from Escherichia coli, which has been the most
      intensively investigated, is a monomeric protein with a molecular mass of about
      18,000. Structures of the enzyme, determined by X-ray crystallography and NMR,
      have shown that it adopts an alpha/beta fold with a substrate-binding cleft on
      the surface. Three loop regions surround the enzyme active site and form intimate
      contacts with the substrates. The enzyme has a fixed order of substrate binding,
      with ATP binding first, followed by HMDP. Binding of ATP causes a shift in the
      conformations of the loop regions, which completes formation of the HMDP-binding
      site. Two magnesium ions bind within the active site, bridging between the
      phosphate groups in ATP and the enzyme. Both ions appear to play an integral role
      in ATP recognition and stabilization of the transition state of the reaction.
      Ligand binding and kinetic studies have shown that the overall rate of the
      reaction is not limited by the rate of substrate transformation into products on
      the enzyme, which is relatively fast, but is more likely caused by a slow step
      associated with product release. These fundamental studies open up the potential
      for exploitation through the design of specific HPPK inhibitors.

PMID- 18804705
TI  - Linking Global Youth Tobacco Survey (GYTS) data to the WHO Framework Convention
      on Tobacco Control.

PMID- 18804706
TI  - Starting to smoke too easily, starting to smoke too young.

PMID- 18804707
TI  - Simply the best.

PMID- 18804708
TI  - ENA Health Care Reform Platform.

PMID- 18804711
TI  - The Geriatric Emergency Nursing Education (GENE) course: an evaluation.
AB  - OBJECTIVE: To evaluate the impact of the GENE course on emergency nurses'
      geriatric best practices in the emergency department (ED). SAMPLE: A convenience
      sample of 102 emergency nurses who attended the GENE course at the San Diego
      convention center on October 3, 2004. METHOD: A prospective method of data
      collection, with data collection before, immediately after, and three months
      after attending the course, was used to evaluate the short-term impact of the
      GENE course on emergency nurses' geriatric knowledge and geriatric care best
      practices. RESULTS: After attending the GENE course, emergency nurses showed
      increased a) knowledge of geriatric concepts (p < .000, alpha = .01) and b) self
      rated ability to provide care in areas such as functional assessment, assessment
      of depression, delirium, dementia, polypharmacy, and appropriate referrals to
      services. ED nurses reported significantly greater utilization of particular
      geriatric assessment tools and greater incorporation of knowledge and skills
      related to the assessment of pain, polypharmacy, elder abuse and neglect, and
      atypical presentation of illness as part of their practice. Finally, a
      significant increase in the number of emergency departments that incorporated
      geriatric protocols of care was reported (p = .003, alpha = .05).

PMID- 18804712
TI  - The impact of ED nurse manager leadership style on staff nurse turnover and
      patient satisfaction in academic health center hospitals.
AB  - INTRODUCTION: Nurse managers with effective leadership skills are an essential
      component to the solution for ending the nursing shortage. Empirical studies of
      existing ED nurse manager leadership styles and their impact on key nurse
      management outcomes such as staff nurse turnover and patient satisfaction have
      not been performed. The specific aims of this study were to determine what types
      of leadership styles were used by ED nurse managers in academic health center
      hospitals and examine their influence on staff nurse turnover and patient
      satisfaction. METHOD: ED nurse managers were asked to complete the Multifactor
      Leadership Questionnaire and a 10-item researcher defined nurse manager role and
      practice demographics survey. Completed surveys (15 managers and 30 staff nurses)
      representing 15 out of 98 possible U.S. academic health centers were obtained.
      RESULTS: Fisher's exact test with 95% confidence intervals were used to analyze
      the data. The sample percentage of managers who exhibited Transformational
      leadership styles and demographic findings of nurse manager age, total years
      experience and length of time in current position matched current reports in the
      literature. A trend of lower staff nurse turnover with Transformational
      leadership style compared to non-Trasformational leadership styles was
      identified. However, the type of leadership style did not appear to have an
      effect on patient satisfaction. DISCUSSION: The ED is an ever-changing, highly
      regulated, critical-care environment. Effective ED nurse manager leadership
      strategies are vital to maintaining the standards of professional emergency
      nursing practice to create an environment that can produce management outcomes of
      decreased staff nurse turnover, thereby enhancing staff nurse retention and
      potentially impacting patient satisfaction.

PMID- 18804713
TI  - Sexual assault nurse examiners' application of statutory rape reporting laws.
AB  - INTRODUCTION: The objective of this study was to compile a list of current state
      laws that mandate medical providers' reporting of statutory rape and assess the
      subjective interpretation of such laws by sexual assault nurse examiners (SANEs)
      throughout the country. METHODS: We contacted an SANE representative from each
      state by use of the International Association of Forensic Nurses' Web site to
      obtain information on his or her interpretation of the respective state's
      statutory rape reporting laws. We compared current state laws and SANE
      interpretation of such laws with legal interpretation of state laws 5 years
      previously. RESULTS: According to practitioners, the number of states that
      legislate mandatory reporting has increased over the past 5 years. State law
      routinely mandates reporting in 26 states and does not mandate reporting in 10
      states. In 3 of those 10, the law prohibits reporting. The law requires reporting
      only under certain conditions in 14 states. DISCUSSION: Practitioner
      interpretation of state laws regarding definitions and mandatory reporting of
      statutory rape varies widely from state to state, and these laws have changed
      significantly in many states over the past 5 years. Practitioners wishing to
      comply with state reporting laws require updated legislation information.

PMID- 18804714
TI  - Evaluating disparities in door-to-EKG time for patients with noncardiac chest
      pain.
AB  - INTRODUCTION: Our objective was to examine gender, racial, and age differences in
      door-to-EKG time in patients diagnosed with non-cardiac chest pain. METHODS: This
      was a prospective cohort study of adult patients with an explicitly stated chief
      complaint of chest pain at an urban, academic ED. Primary study outcome variable
      was time to initial EKG. Predictor variables included gender, race, and age.
      RESULTS: The final sample consisted of 214 patients. The overall median time to
      EKG in this cohort of patients was 29 minutes. No difference in time to EKG was
      found between gender or racial category. Time to EKG was significantly greater
      for patients in age categories 18-39 and 40-59 when compared with subjects
      greater than 60 years old. DISCUSSION: In this prospective cohort study of non
      STEMI/ACS patients with a chief complaint of chest pain, there were no gender or
      racial disparities in door-to-EKG time.

PMID- 18804715
TI  - Visits coded as intimate partner violence in emergency departments:
      characteristics of the individuals and the system as reported in a national
      survey of emergency departments.
AB  - INTRODUCTION: This study was conducted to explore the characteristics of intimate
      partner violence (IPV) victims whose visit was coded as IPV and the health care
      delivery system in emergency departments (ED). METHODS: This study utilized a
      secondary data analysis of a national probability sample that comprised the
      National Hospital Ambulatory Medical Care Survey for 1997 to 2001. RESULTS: There
      were 111 coded ED visits of IPV victims 16 years or older (equivalent of 482,979
      out of 4 million national visits for the 5-year study period). Women (94%),
      African Americans (35%), those 25 to 44 years of age (64%), and uninsured
      patients (38%) were significantly more likely to be categorized as an IPV visit
      (odds ratios 14, 1.9, 2.7, and 2.4, respectively) compared with non-IPV visits.
      Characteristics of the health care delivery system (region, metropolitan vs. non
      metropolitan, type of hospital, and type of health care provider) were not
      associated with IPV. DISCUSSION: Caution should be implemented when interpreting
      the study results because they represent only coded IPV visits in the emergency
      department. The study findings suggest the critical need to improve
      identification, documentation, and coding of IPV visits.

PMID- 18804716
TI  - QT/QTc interval monitoring in the emergency department.

PMID- 18804717
TI  - Transitioning from novice to competent: what can we learn from the literature
      about graduate nurses in the emergency setting?

PMID- 18804718
TI  - ED overcrowding: an assessment tool to monitor ED registered nurse workload that
      accounts for admitted patients residing in the emergency department.

PMID- 18804719
TI  - September 11th.

PMID- 18804720
TI  - A 49-year-old woman with acute mastoiditis, meningitis, and subdural empyema.

PMID- 18804722
TI  - Psychiatric nurse: a role in overcrowding.

PMID- 18804723
TI  - Development of a psychiatric crisis stabilization unit.

PMID- 18804724
TI  - Fatal errors with cerebyx.

PMID- 18804725
TI  - A four-letter word: Vote!

PMID- 18804726
TI  - Reading and Abstracting the Literature: part II.

PMID- 18804727
TI  - Effects of ED diversion on trauma care as perceived by EMTs who provide basic
      life support services for Morristown Memorial Hospital's geographical region.

PMID- 18804728
TI  - Cardiac injury and death by lightning strike.

PMID- 18804729
TI  - Reporting injuries from products.

PMID- 18804730
TI  - The development of a medical service learning study-away program.

PMID- 18804732
TI  - Advanced practice nurse role in community partnership for education.

PMID- 18804733
TI  - Big help from little tools.

PMID- 18804734
TI  - Devious digoxin: a case review.

PMID- 18804735
TI  - Dog bites: a brief case review.

PMID- 18804736
TI  - A critical appraisal of implantable cardioverter-defibrillator therapy for the
      prevention of sudden cardiac death.
AB  - The indications for implantable cardioverter-defibrillators (ICDs) for the
      prevention of sudden cardiac death have rapidly expanded over the past 10 years.
      Clinical trial data have quickly been implemented into guidelines without
      critical reassessment of the strengths and limitations of the evidence. ICD
      therapy has inherent risks including infection, unnecessary shocks, potential for
      proarrhythmia, device malfunction, highly publicized manufacturer advisories, and
      procedural complications, which can adversely affect morbidity and quality of
      life. A reappraisal of the benefits and potential hazards of ICD therapy will
      enable physicians to a have a more mutually informed and balanced dialogue with
      their patients.

PMID- 18804737
TI  - Benefits of the implantable cardioverter-defibrillator.
AB  - The state-of-the-art review by Tung and colleagues provides a thoughtful
      perspective on balancing the benefits and risks of implantable cardioverter
      defibrillator (ICD) therapy addressing the concerns of many caring physicians. In
      this response: 1) the clinical benefits of ICD therapy are reviewed using the
      evidence base resulting from controlled clinical trials; 2) untoward effects of
      ICDs on quality of life are acknowledged, and it is argued that they do not
      negate the results of studies in which the aggregate show benefit; and 3) cost
      effectiveness of ICD therapy is considered. Although clinical trials evaluating
      ICD therapy have limitations, there are few interventions in which multiple trial
      settings have consistently over a >10-year period produced a 20% to 30% reduction
      in total mortality. Research to better identify patients expected to benefit from
      ICD therapy is ongoing, but at present we have the results of clinical trials
      that show improved survival in a broad selection of patients with left
      ventricular dysfunction and either demonstrated or anticipated risk for
      arrhythmic death. Evidence-based medicine; the rigorous process of guideline
      writing, review, and approval; and the ethical consideration of offering proven
      life-prolonging therapies to all patients provide a compelling rationale for
      clinicians to carefully consider guidelines in their clinical decision making.
      Updates in the new Device-Based Therapy Guidelines for the implantation of ICDs
      and pacemakers advance these goals.

PMID- 18804738
TI  - Point-of-care measurement of clopidogrel responsiveness predicts clinical outcome
      in patients undergoing percutaneous coronary intervention results of the ARMYDA
      PRO (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty
      Platelet Reactivity Predicts Outcome) study.
AB  - OBJECTIVES: The aim of this study was to evaluate the correlation of point-of
      care measurement of platelet inhibition with clinical outcome in patients
      undergoing percutaneous coronary intervention (PCI). BACKGROUND: Individual
      variability of clopidogrel response might influence results of PCI. METHODS: A
      total of 160 patients receiving clopidogrel before PCI were prospectively
      enrolled. Platelet reactivity was measured by the VerifyNow P2Y12 assay
      (Accumetrics Inc., San Diego, California). Primary end point was 30-day
      occurrence of major adverse cardiac events (MACE) according to quartile
      distribution of P2Y12 reaction units (PRU). RESULTS: Primary end point occurred
      more frequently in patients with pre-procedural PRU levels in the fourth quartile
      versus those in the lowest quartile (20% vs. 3%; p=0.034), and it was entirely
      due to periprocedural myocardial infarction (MI). Mean PRU absolute levels were
      higher in patients with periprocedural MI (258+/-53 vs. 219+/-69 in patients
      without; p=0.030). On multivariable analysis pre-PCI PRU levels in the fourth
      quartile were associated with 6-fold increased risk of 30-day MACE (odds ratio:
      6.1; 95% confidence interval: 1.1 to 18.3, p=0.033). By receiver-operating
      characteristic curve analysis, the optimal cut-off for the primary end point was
      a pre-PCI PRU value>or=240 (area under the curve: 0.69; 95% confidence interval:
      0.56 to 0.81, p=0.016). CONCLUSIONS: This study indicates that high pre-PCI
      platelet reactivity might predict 30-day events. Use of a rapid point-of-care
      assay for monitoring residual platelet reactivity after clopidogrel
      administration might help identify patients in whom individualized antiplatelet
      strategies might be indicated with coronary intervention.

PMID- 18804739
TI  - Incidence and correlates of drug-eluting stent thrombosis in routine clinical
      practice. 4-year results from a large 2-institutional cohort study.
AB  - OBJECTIVES: We sought to determine the risk of late stent thrombosis (ST) during
      long-term follow-up beyond 3 years, searched for predictors, and assessed the
      impact of ST on overall mortality. BACKGROUND: Late ST was reported to occur at
      an annual rate of 0.6% up to 3 years after drug-eluting stent (DES) implantation.
      METHODS: A total of 8,146 patients underwent percutaneous coronary intervention
      with a sirolimus-eluting stent (SES) (n=3,823) or paclitaxel-eluting stent (PES)
      (n=4,323) and were followed up to 4 years after stent implantation. Dual
      antiplatelet treatment was prescribed for 6 to 12 months. RESULTS: Definite ST
      occurred in 192 of 8,146 patients with an incidence density of 1.0/100 patient
      years and a cumulative incidence of 3.3% at 4 years. The hazard of ST continued
      at a steady rate of 0.53% (95% confidence interval [CI]: 0.44 to 0.64) between 30
      days and 4 years. Diabetes was an independent predictor of early ST (hazard ratio
      [HR]: 1.96; 95% CI: 1.18 to 3.28), and acute coronary syndrome (HR: 2.21; 95% CI:
      1.39 to 3.51), younger age (HR: 0.97; 95% CI: 0.95 to 0.99), and use of PES (HR:
      1.67; 95% CI: 1.08 to 2.56) were independent predictors of late ST. Rates of
      death and myocardial infarction at 4 years were 10.6% and 4.6%, respectively.
      CONCLUSIONS: Late ST occurs steadily at an annual rate of 0.4% to 0.6% for up to
      4 years. Diabetes is an independent predictor of early ST, whereas acute coronary
      syndrome, younger age, and PES implantation are associated with late ST.

PMID- 18804740
TI  - Statins, low-density lipoprotein cholesterol, and risk of cancer.
AB  - OBJECTIVES: We sought to assess whether statin-mediated reductions in low-density
      lipoprotein cholesterol (LDL-C) are associated with an increased risk of cancer.
      BACKGROUND: We recently reported an inverse association between on-treatment LDL
      C levels and incident cancer in statin-treated patients enrolled in large
      randomized controlled trials, raising concern that LDL-C lowering by statins may
      increase cancer risk. However, meta-analyses suggest a neutral overall effect of
      statins on incident cancer. METHODS: A systematic literature search identified 15
      eligible randomized controlled trials of statins with >or=1,000 person-years of
      follow-up that provided on-treatment LDL-C levels and rates of incident cancers
      (19 statin and 14 control arms, 437,017 person-years cumulative follow-up, and
      5,752 incident cancers). RESULTS: In the statin arms, meta-regression analysis
      demonstrated an inverse association between on-treatment LDL-C and incident
      cancer, with an excess of 2.2 (95% confidence interval: 0.7 to 3.6) cancers per
      1,000 person-years for every 10 mg/dl decrement in on-treatment LDL-C (p=0.006).
      The corresponding difference among control arms was 1.2 (95% confidence interval:
      -0.2 to 2.7, p=0.09). Compared with the control arms, the statin regression line
      was significantly shifted leftward, such that similar rates of incident cancer
      were associated with lower on-treatment LDL-C (p<0.05). Meta-regression
      demonstrated that statins lack an effect on cancer risk across all levels of on
      treatment LDL-C. CONCLUSIONS: There is an inverse association between on
      treatment LDL-C and incident cancer. However, statins, despite producing marked
      reductions in LDL-C, are not associated with an increased risk of cancer.

PMID- 18804741
TI  - Statin treatment does not cause cancer.

PMID- 18804742
TI  - Low LDL-C levels and cancer reassuring but still not definitive.

PMID- 18804743
TI  - Subclinical thyroid dysfunction, cardiac function, and the risk of heart failure.
      The Cardiovascular Health study.
AB  - OBJECTIVES: The goal of this study was to determine whether subclinical thyroid
      dysfunction was associated with incident heart failure (HF) and echocardiogram
      abnormalities. BACKGROUND: Subclinical hypothyroidism and hyperthyroidism have
      been associated with cardiac dysfunction. However, long-term data on the risk of
      HF are limited. METHODS: We studied 3,044 adults>or=65 years of age who initially
      were free of HF in the Cardiovascular Health Study. We compared adjudicated HF
      events over a mean 12-year follow-up and changes in cardiac function over the
      course of 5 years among euthyroid participants, those with subclinical
      hypothyroidism (subdivided by thyroid-stimulating hormone [TSH] levels: 4.5 to
      9.9, >or=10.0 mU/l), and those with subclinical hyperthyroidism. RESULTS: Over
      the course of 12 years, 736 participants developed HF events. Participants with
      TSH>or=10.0 mU/l had a greater incidence of HF compared with euthyroid
      participants (41.7 vs. 22.9 per 1,000 person years, p=0.01; adjusted hazard
      ratio: 1.88; 95% confidence interval: 1.05 to 3.34). Baseline peak E velocity,
      which is an echocardiographic measurement of diastolic function associated with
      incident HF in the CHS cohort, was greater in those patients with TSH>or=10.0
      mU/l compared with euthyroid participants (0.80 m/s vs. 0.72 m/s, p=0.002). Over
      the course of 5 years, left ventricular mass increased among those with
      TSH>or=10.0 mU/l, but other echocardiographic measurements were unchanged. Those
      patients with TSH 4.5 to 9.9 mU/l or with subclinical hyperthyroidism had no
      increase in risk of HF. CONCLUSIONS: Compared with euthyroid older adults, those
      adults with TSH>or=10.0 mU/l have a moderately increased risk of HF and
      alterations in cardiac function but not older adults with TSH<10.0 mU/l. Clinical
      trials should assess whether the risk of HF might be ameliorated by thyroxine
      replacement in individuals with TSH>or=10.0 mU/l.

PMID- 18804744
TI  - Prevalence of different gadolinium enhancement patterns in patients after heart
      transplantation.
AB  - OBJECTIVES: Transplant coronary artery disease (TCAD) limits long-term survival
      after heart transplantation (HTX). We hypothesized that contrast-enhanced
      magnetic resonance imaging (CE-MRI) detects chronic TCAD-related myocardial
      infarctions (MIs), even in patients with angiographically classified mild TCAD.
      BACKGROUND: Coronary angiography underestimates the TCAD-degree, subsequently
      missing occluded small coronary arteries and resulting MI. CE-MRI as a
      noninvasive imaging technique identifies infarct-typical MI and myocardial
      fibrosis. METHODS: CE-MRI (gadolinium: 0.2 mmol/kg/bw) was performed in 53 HTX
      patients on a 1.5-T MRI scanner (Philips, Best, the Netherlands). Infarct-typical
      CE-MRI areas were classified as: I=<or=25%, II=25% to 50%, III=50% to 75% and
      IV=>or=75%. Infarct-atypical forms were divided into diffuse, spotted,
      intramural, and infero-septal. Coronary angiography results were reviewed
      qualitatively with the TCAD score (TCAD I=mild evidence; II=30% to 75%,
      III=>or=75% stenosis). Groups were compared with analysis of variance
      (statistically significant p values<or=0.05). RESULTS: Infarct-typical CE-MRI was
      already present in TCAD I+II, increased significantly between groups (I=23%,
      II=33%, III=84%, p<0.05), and involved only single coronary territories in TCAD I
      but multiple vessels in TCAD II+III. Infarct-atypical CE-MRI was equally
      distributed across all TCAD stages (I=50% vs. II=58% vs. III=42%, p=NS) without
      relation to a coronary territory. Patients with only infarct-atypical CE-MRI were
      associated with significantly better left ventricular function compared with
      patients with infarct-typical or combined CE-MRI patterns (ejection fraction=66+/
      6% vs. 45+/-16% or 60+/-13%; end-diastolic volume=139+/-32 ml vs. 148+/-27 ml or
      164+/-43 ml; end-systolic volume=47+/-15 ml vs. 81+/-27 ml or 69+/-38 ml,
      p<or=0.05). CONCLUSIONS: CE-MRI allows identification of silent MI in apparently
      event-free HTX patients and is able to disclose myocardial fibrosis already in
      patients with absent or mild angiographic TCAD. CE-MRI might be helpful to
      establish an earlier TCAD diagnosis and to intensify medical treatment. Future
      studies are necessary to test prognostic implications associated with CE-MRI
      patterns.

PMID- 18804745
TI  - Contrast-enhanced magnetic resonance imaging as the newest tool to detect
      transplant coronary artery disease.

PMID- 18804746
TI  - The role of false lumen size in prediction of in-hospital complications after
      acute type B aortic dissection.
AB  - OBJECTIVES: The aim of this study was to determine whether false lumen size
      predicts in-hospital complications for acute type B aortic dissection.
      BACKGROUND: The incidence of complications developing in patients with acute type
      B aortic dissection has been high. However, methods for recognizing high-risk
      patients have not been well-studied. We used quantitative analysis by computed
      tomography (CT) to predict the occurrence of in-hospital complications. METHODS:
      Fifty-five consecutive patients with acute type B aortic dissection documented by
      CT imaging were analyzed. They were divided into groups, with and without in
      hospital complications, and compared regarding maximal aortic diameter (MAD),
      maximal false lumen area (MFLA), minimal true lumen area (MTLA), branch-vessel
      involvement (BVI), and longitudinal length (LL) of aortic dissection. RESULTS:
      There were 31 patients with a stable course (group 1) and 24 patients who
      developed complications (group 2). The MFLA of group 2 was significantly larger
      than that of group 1 (group 1 vs. group 2=577.7+/-273.2 mm2 vs. 1,899.3+/-1,642.4
      mm2, p<0.001). The BVI number was also higher in group 2 (group 1 vs. group
      2=1.0+/-1.1 vs. 3.3+/-2.0, p<0.001). On multivariate analysis, only MFLA and BVI
      number were independent predictors of in-hospital complications. Patients with
      initial MFLA>or=922 mm2 or BVI number>or=2 showed a significantly higher
      incidence of in-hospital complications than the other patients (p<0.001).
      CONCLUSIONS: A large MFLA and a higher BVI number are powerful predictors of in
      hospital complications after acute type B aortic dissection.

PMID- 18804748
TI  - Deciphering gene expression profiling in cardiac resynchronization therapy.

PMID- 18804749
TI  - American Heart Association/American College of Cardiology Foundation/Heart Rhythm
      Society Scientific Statement on Noninvasive Risk Stratification Techniques for
      Identifying Patients at Risk for Sudden Cardiac Death. A scientific statement
      from the American Heart Association Council on Clinical Cardiology Committee on
      Electrocardiography and Arrhythmias and Council on Epidemiology and Prevention.

PMID- 18804750
TI  - A study in desmotropy.
AB  - A solid-state NMR/theoretical study of the tautomerism of 4-substituted
      pyrazolinones was carried out in search of new desmotropes. Thus, the systematic
      exploration by (13)C and (15)N CPMAS NMR of a series of 4-acylpyrazolin-5-ones
      has allowed to determine their structure in the solid state and to find a new
      example of desmotropy that of 1-phenyl-4-acetyl-pyrazolinone.

PMID- 18804752
TI  - Attention to smoking-related and incongruous objects during scene viewing.
AB  - This study examined the influences of semantic characteristics of objects in real
      world scenes on allocation of attention as reflected in eye movement measures.
      Stimuli consisted of full-color photographic scenes, and within each scene, the
      semantic salience of two target objects was manipulated while the objects'
      perceptual salience was kept constant. One of the target objects was either
      inconsistent or consistent with the scene category. In addition, the second
      target object was either smoking-related or neutral. Two groups of college
      students, namely current cigarette smokers (N=18) and non-smokers (N=19), viewed
      each scene for 10s while their eye movements were recorded. While both groups
      showed preferential allocation of attention to inconsistent objects, smokers also
      selectively attended to smoking-related objects. Theoretical implications of the
      results are discussed.

PMID- 18804753
TI  - Filling-in visual motion with sounds.
AB  - Information about the motion of objects can be extracted by multiple sensory
      modalities, and, as a consequence, object motion perception typically involves
      the integration of multi-sensory information. Often, in naturalistic settings,
      the flow of such information can be rather discontinuous (e.g. a cat racing
      through the furniture in a cluttered room is partly seen and partly heard). This
      study addressed audio-visual interactions in the perception of time-sampled
      object motion by measuring adaptation after-effects. We found significant
      auditory after-effects following adaptation to unisensory auditory and visual
      motion in depth, sampled at 12.5 Hz. The visually induced (cross-modal) auditory
      motion after-effect was eliminated if visual adaptors flashed at half of the rate
      (6.25 Hz). Remarkably, the addition of the high-rate acoustic flutter (12.5 Hz)
      to this ineffective, sparsely time-sampled, visual adaptor restored the auditory
      after-effect to a level comparable to what was seen with high-rate bimodal
      adaptors (flashes and beeps). Our results suggest that this auditory-induced
      reinstatement of the motion after-effect from the poor visual signals resulted
      from the occurrence of sound-induced illusory flashes. This effect was found to
      be dependent both on the directional congruency between modalities and on the
      rate of auditory flutter. The auditory filling-in of time-sampled visual motion
      supports the feasibility of using reduced frame rate visual content in
      multisensory broadcasting and virtual reality applications.

PMID- 18804754
TI  - Characterization and potential applications of nanostructured aqueous
      dispersions.
AB  - The present article highlights recent advances and current status in the
      characterization and the utilization of nanostructured aqueous dispersions in
      which the submicron-sized dispersed particles envelope a distinctive well-defined
      self-assembled interior. The scope of this review covers dispersions of both
      inverted-type liquid-crystalline particles (cubosomes, hexosomes, micellar
      cubosomes, and sponge phases), and microemulsion droplets (emulsified
      microemulsions, EMEs). Recent investigations that have attempted to shed light on
      the characterization and the control of confined nanostructures of aqueous
      dispersions are surveyed, as these nanoobjects are attractive for various
      pharmaceutical and food applications. The focus has been placed on three main
      subjects: (1) our findings on the formation of EMEs and the modulation of the
      internal nanostructure, exploring how variations in temperature, oil content, and
      lipid composition significantly affect the confined nanostructures; (2) recent
      developments in the field of electron microscopy: using the tilt-angle cryo-TEM
      method or cryo-field emission scanning electron microscopy (cryo-FESEM) for
      observing the three dimensional (3D) morphology of non-lamellar liquid
      crystalline nanostructured particles (cubosome and hexosome particles); and (3)
      recent studies on the utilization of nanostructured dispersions as drug
      nanocarriers.

PMID- 18804755
TI  - The synthesis and biological evaluation of some carbocyclic analogues of PUGNAc.
AB  - The synthesis of some analogues of O-(2-acetamido-2-deoxy-D
      glucopyranosylidene)amino N-phenylcarbamate, PUGNAc, an inhibitor of beta-N
      acetylglucosaminidases, is described. The analogues were tested against a range
      of beta-N-acetylglucosaminidases to establish any biological activity. As well,
      the analogues were tested as inhibitors of a uridine diphosphate-N-acetyl-D
      glucosamine: polypeptidyl transferase, OGT, a critical protein involved in the
      post-translational modification of nuclear and cytosolic proteins by N-acetyl-d
      glucosamine.

PMID- 18804757
TI  - Effects of radiofrequency electromagnetic waves (RF-EMW) from cellular phones on
      human ejaculated semen: an in vitro pilot study.
AB  - OBJECTIVE: To evaluate effects of cellular phone radiofrequency electromagnetic
      waves (RF-EMW) during talk mode on unprocessed (neat) ejaculated human semen.
      DESIGN: Prospective pilot study. SETTING: Center for reproductive medicine
      laboratory in tertiary hospital setting. SAMPLES: Neat semen samples from normal
      healthy donors (n = 23) and infertile patients (n = 9). INTERVENTION(S): After
      liquefaction, neat semen samples were divided into two aliquots. One aliquot
      (experimental) from each patient was exposed to cellular phone radiation (in talk
      mode) for 1 h, and the second aliquot (unexposed) served as the control sample
      under identical conditions. MAIN OUTCOME MEASURE(S): Evaluation of sperm
      parameters (motility, viability), reactive oxygen species (ROS), total
      antioxidant capacity (TAC) of semen, ROS-TAC score, and sperm DNA damage.
      RESULT(S): Samples exposed to RF-EMW showed a significant decrease in sperm
      motility and viability, increase in ROS level, and decrease in ROS-TAC score.
      Levels of TAC and DNA damage showed no significant differences from the unexposed
      group. CONCLUSION(S): Radiofrequency electromagnetic waves emitted from cell
      phones may lead to oxidative stress in human semen. We speculate that keeping the
      cell phone in a trouser pocket in talk mode may negatively affect spermatozoa and
      impair male fertility.

PMID- 18804758
TI  - Effect of levonorgestrel implants on the periodontium.

PMID- 18804756
TI  - The structure of the L9 immunotype lipooligosaccharide from Neisseria
      meningitidis NMA Z2491.
AB  - The lipooligosaccharide (LOS) from the Neisseria meningitidis prototype serogroup
      A strain NMA Z2491, an L9 immunotype LOS, was isolated and structurally
      characterized using glycosyl composition and linkage determination, mass
      spectrometry, and both 1- and 2-D nuclear resonance spectroscopy. The results
      show that the L9 LOS has an identical structure to that of an L4 LOS structure
      with the exception that it does not contain a sialic acid residue linked to
      position 3 of the lactoneotetraose terminal galactosyl residue. Further, two
      oligosaccharides are present in the Z2491 LOS preparation, OS1 and OS2. They
      differ from one another only in that OS2 contains an added glycine moiety,
      presumably at O-7 on the inner core Hep II residue. The structures of these
      oligosaccharides are as follows: where R=H or Gly.

PMID- 18804759
TI  - Metabolic syndrome, haemostatic and inflammatory markers, cerebrovascular and
      peripheral arterial disease: The Edinburgh Artery Study.
AB  - The role of metabolic syndrome and associated haemostatic and inflammatory
      markers in risk of atherosclerosis in different vascular beds is controversial.
      We used modified National Cholesterol Education Program criteria to define
      metabolic syndrome in a population-based cohort of men and women aged 55-74 years
      with up to 15 years of follow-up to investigate whether metabolic syndrome is
      associated with risk of cerebrovascular and peripheral arterial disease and the
      role of inflammatory and haemostatic factors in these relationships. Data were
      available for 762 participants, of whom 267 (35%) had metabolic syndrome at
      baseline and 69 (9.0%) and 108 (14%) had cerebrovascular and peripheral arterial
      disease events, respectively, during follow-up. We used Cox proportional hazards
      modelling to estimate hazard ratios (HRs). Metabolic syndrome was associated with
      several haemostatic and inflammatory variables and with cerebrovascular disease
      both after adjusting for age and sex (HR 2.12 (1.31-3.41) and after further
      adjustment for conventional cardiovascular risk factors and inflammatory and
      haemostatic markers (HR 1.77 (1.05-2.96). The association between metabolic
      syndrome and peripheral arterial disease was not statistically significant either
      with adjustment for age and sex (HR 1.33 (0.90-1.96) or after full adjustment (HR
      0.89 (0.57-1.38). We conclude that metabolic syndrome was more strongly related
      to risk of atherosclerosis in the cerebrovascular than the peripheral circulation
      and the association was independent of conventional risk factors, haemostatic and
      inflammatory markers in this population. Improving insulin sensitivity may reduce
      cerebrovascular disease risk.

PMID- 18804760
TI  - Genetic and pharmacological inhibition of the 5-lipoxygenase/leukotriene pathway
      in atherosclerotic lesion development in ApoE deficient mice.
AB  - The 5-lipoxygenase (5-LO) catalyzed formation of leukotriene (LT) lipid mediators
      is a pathway contributing to inflammatory events in asthma and more recently has
      been associated with cardiovascular disease. However, the relative impact of this
      pathway in atherogenesis has been controversial and a variety of mixed results
      reported. The goal of these studies was to assess the importance of the 5-LO/LT
      pathway in mice with either genetic (5-LO(-/-)) or pharmacological (L-739,010)
      inhibition of the 5-LO pathway on an apolipoprotein E deficient (apoE(-/-))
      background when subjected to either an 8-week (Paigen) or 6 months (Western)
      atherosclerotic diet regimen. Atherosclerotic lesion analysis at the aortic root,
      brachiocephalic artery and throughout the whole aorta by en face Sudan IV
      staining was determined, as well as blood lipid levels. Ex vivo calcium ionophore
      stimulation of whole blood demonstrated a significant reduction in the capacity
      to form LTB(4) in 5-LO(-/-) and drug-treated 5-LO(+/+) mice. Quantitative
      analysis of atherosclerotic lesions did not differ between groups at all three
      sites. Moreover, the composition of advanced lesions in the brachiocephalic
      arteries did not indicate altered plaque disruption as a result of 5-LO gene
      inactivation. These results do not support a role for the 5-LO/LT pathway in
      intermediate to advanced atherosclerotic lesion development in mice.

PMID- 18804761
TI  - Strong complement activation after acute ischemic stroke is associated with
      unfavorable outcomes.
AB  - OBJECTIVE: According to data from animal models, complement activation plays a
      major role in the brain injury after acute ischemic stroke. Scarce findings are,
      however, available on the detection of complement activation products in stroke
      patients. METHODS: We have measured plasma levels of the five complement
      activation products (C1rC1sC1inh, C4d, C3a, C5a and SC5b-9) in samples of 26
      patients with ischemic stroke upon admission. Twenty-six patients with severe
      carotid atherosclerosis served as patient controls. RESULTS: Levels of two
      activation products (SC5b-9 and C4d)) were significantly elevated in the plasma
      of stroke patients, SC5b-9 levels, exhibited significant positive correlation
      with the clinical severity of stroke, the severity of neurological deficit, as
      well as with the level of functional disability. CONCLUSION: These findings
      suggest that complement activation plays an active role in the development of
      brain infarct. The measurement of complement activation products might help to
      determine the clinical prognosis after acute ischemic stroke. Furthermore, there
      is potential usefulness of complement modulating therapy in ischemic stroke.

PMID- 18804762
TI  - Association between IL-6 and the extent of coronary atherosclerosis in the
      veterans affairs diabetes trial (VADT).
AB  - AIMS: The aim of the present study was to investigate the association of high
      sensitivity C-reactive protein (CRP), interleukin-6 (IL-6) and lipoprotein
      associated phospholipase A2 (Lp-PLA2) with the extent of calcified coronary
      atherosclerosis in patients with type 2 diabetes mellitus (T2DM). MATERIALS AND
      RESULTS: This is a cross-sectional study of 306 subjects aged 40years or older
      who were enrolled into the veterans affairs diabetes trial (VADT). Calcified
      coronary atherosclerosis was assessed using electron beam computed tomography
      scored by the Agatston method. Clinical parameters, traditional cardiovascular
      risk factors and plasma levels of CRP, IL-6 and Lp-PLA2 were measured at the time
      of the scan. Coronary artery calcium (CAC) scores increased stepwise across
      increasing categories of IL-6, but did not change across increasing categories of
      CRP and Lp-PLA2. After adjustment for traditional cardiovascular risk factors, IL
      6 was significantly associated with CAC scores (p=0.05). The association between
      IL-6 and CAC was largely in those with lower (below the median) abdominal artery
      calcium (AAC) levels (p=0.04). CONCLUSIONS: Despite a generally higher level of
      systemic inflammation in T2DM, the inflammatory marker IL-6 remained
      significantly associated with CAC score, particularly in those subjects with
      lower AAC scores.

PMID- 18804763
TI  - Validation of a musculoskeletal model of wheelchair propulsion and its
      application to minimizing shoulder joint forces.
AB  - The majority of manual wheelchair users (MWUs) will inevitably develop some
      degree of shoulder pain over time. Previous research has suggested a link between
      the shoulder joint forces associated with the repetition of wheelchair (WC)
      propulsion and pain. The objective of this work is to present and validate a
      rigid-body musculoskeletal model of the upper limb for calculation of shoulder
      joint forces throughout WC propulsion. It is anticipated that when prescribing a
      WC, the use of a patient-specific computational model will aide in determining an
      axle placement in which shoulder joint forces are at a minimum, thus potentially
      delaying or reducing the shoulder pain that so many MWUs experience. During the
      validation experiment, 3 subjects (2 individuals with paraplegia and one able
      bodied individual) propelled a WC at a self-selected speed, during which,
      kinematics, kinetics, and electromyography (EMG) activity were measured for the
      contact phase of 10 consecutive push strokes. The measured forces at the push rim
      and the 3-D propulsion kinematics drove the model, and the computationally
      calculated muscle activities were compared with the experimental muscle
      activities, resulting in an average mean absolute error (MAE) of 0.165. Further
      investigation of the shoulder joint forces throughout propulsion demonstrate the
      effect of axle placement on the magnitude of these forces. The present work
      serves to validate the patient-specific upper limb model for use as a
      prescriptive tool for fitting a subject to their WC. Minimizing joint forces from
      injury onset may prolong a MWU's pain-free way of life.

PMID- 18804764
TI  - Mechanical modeling of self-expandable stent fabricated using braiding
      technology.
AB  - The mechanical behavior of a stent is one of the important factors involved in
      ensuring its opening within arterial conduits. This study aimed to develop a
      mechanical model for designing self-expandable stents fabricated using braiding
      technology. For this purpose, a finite element model was constructed by
      developing a preprocessing program for the three-dimensional geometrical modeling
      of the braiding structure inside stents, and validated for various stents with
      different braiding structures. The constituent wires (Nitinol) in the braided
      stents were assumed to be superelastic material and their mechanical behavior was
      incorporated into the finite element software through a user material subroutine
      (VUMAT in ABAQUS) employing a one-dimensional superelastic model. For the
      verification of the model, several braided stents were manufactured using an
      automated braiding machine and characterized focusing on their compressive
      behavior. It was observed that the braided stents showed a hysteresis between
      their loading and unloading behavior when a compressive load was applied to the
      braided tube. Through the finite element analysis, it was concluded that the
      current mechanical model can appropriately predict the mechanical behavior of
      braided stents including such hysteretic behavior, and that the hysteresis was
      caused by the slippage between the constituent wires and their superelastic
      property.

PMID- 18804765
TI  - Ground reaction forces and impulses during a transient turning maneuver.
AB  - Understanding the kinetic strategies of turning as expressed in ground reaction
      forces (GRFs) and impulses (GRIs) is necessary to design therapies and
      technologies to enable patients with ambulatory difficulties perform daily
      activities. Previous studies have reported data only for one step of the turn and
      expressed the data in terms of a global reference frame making it difficult to
      understand how the forces act on the body to cause a change in heading and
      orientation during a turn. This study is the first to report GRF and GRI data for
      three steps of a turn and express that data in terms of a body reference frame.
      Motion and GRF data were collected from 10 subjects walking at self-selected
      speeds along a straight path and performing 90 degrees left and right turns.
      During the left turn, turn initiation and apex steps were collected. During the
      right turn, turn termination steps were collected. GRF data were rotated to a
      reference frame whose origin was the body center of mass (COM) and aligned to the
      COM trajectory and then integrated to find the GRIs. In the medial-lateral
      direction, straight steps were characterized by a brief medial impulse at heel
      strike followed by a prolonged lateral impulse. Turn initiation and termination
      steps were both characterized by medial impulses spanning the entire stance phase
      while apex steps were characterized by a large lateral impulse. In the anterior
      posterior direction, initiation steps had larger braking and smaller propulsive
      impulses than straight steps. Apex steps had larger propulsive impulses than
      straight steps, and termination steps had smaller braking and larger propulsive
      impulses than straight steps.

PMID- 18804766
TI  - Measurement of the transverse strain tensor in the coronary arterial wall from
      clinical intravascular ultrasound images.
AB  - Atherosclerotic plaque rupture is the major cause of acute coronary syndromes.
      Currently, there is no reliable diagnostic tool to predict plaque rupture.
      Knowledge of plaque mechanical properties based on local artery wall strain
      measurements would be useful for characterizing its composition and predicting
      its vulnerability. Due to cardiac motion, strain estimation in clinical
      intravascular ultrasound (IVUS) images is extremely challenging. A method is
      presented to estimate cross-sectional coronary artery wall strain in response to
      cardiac pulsatile pressure using clinically acquired IVUS images, which are
      acquired in continuous pullback mode. First, cardiac phase information is
      retrieved retrospectively from an IVUS image sequence using an image-based gating
      method, and image sub-sequences at systole and diastole are extracted. Then,
      images at branch sites are used as landmarks to align the two image sub
      sequences. Finally, the paired images at each site are registered to measure the
      2D strain tensor of the coronary artery cross-section. This method has been
      successfully applied to IVUS images of a left anterior descending (LAD) coronary
      artery acquired clinically during a standard procedure. Such complete strain
      information should be useful for identifying vulnerable plaque.

PMID- 18804767
TI  - Muscle function may depend on model selection in forward simulation of normal
      walking.
AB  - The purpose of this study was to quantify how the predicted muscle function would
      change in a muscle-driven forward simulation of normal walking when changing the
      number of degrees of freedom in the model. Muscle function was described by
      individual muscle contributions to the vertical acceleration of the center of
      mass (COM). We built a two-dimensional (2D) sagittal plane model and a three
      dimensional (3D) model in OpenSim and used both models to reproduce the same
      normal walking data. Perturbation analysis was applied to deduce muscle function
      in each model. Muscle excitations and contributions to COM support were compared
      between the 2D and 3D models. We found that the 2D model was able to reproduce
      similar joint kinematics and kinetics patterns as the 3D model. Individual muscle
      excitations were different for most of the hip muscles but ankle and knee muscles
      were able to attain similar excitations. Total induced vertical COM acceleration
      by muscles and gravity was the same for both models. However, individual muscle
      contributions to COM support varied, especially for hip muscles. Although there
      is currently no standard way to validate muscle function predictions, a 3D model
      seems to be more appropriate for estimating individual hip muscle function.

PMID- 18804768
TI  - Innovative method for determining glycogen content in the Pacific oyster
      (Crassostrea gigas) by ion chromatography.
AB  - A precise analytical assay was developed and validated for the determination of
      Pacific oyster glycogen using ion chromatography. The Pacific oyster glycogen was
      quantified by the determination of glucose-6-phosphate (Glc-6-P), which was
      derived from glucose that was hydrolyzed from glycogen. Glc-6-P, adenosine
      triphosphate, and adenosine diphosphate were separated by ion chromatography. The
      method was validated over the curve range 0.5-100mg/L for the abovementioned
      analytes. The recoveries were between 95% and 102%. The relative standard
      deviations (RSDs, c=10mg/L, n=9) were less than 4.37%. Unlike a traditional
      method, this validated method was inexpensive and stable.

PMID- 18804769
TI  - Phytochemical analysis of traditional Chinese medicine using liquid
      chromatography coupled with mass spectrometry.
AB  - Traditional Chinese medicine (TCM) is commonly considered to operate due to the
      synergistic effects of all the major and minor components in the medicines. Hence
      sensitive and comprehensive analytical techniques are needed to acquire a better
      understanding of the pharmacological basis of the herb and to enhance the product
      quality control. The present review mainly focuses on the phytochemical analysis
      of TCMs using high-performance liquid chromatography coupled with mass
      spectrometry (HPLC-MS). Atmospheric pressure chemical ionization (APCI) and
      electrospray ionization (ESI) are the two commonly used ion sources. Triple
      quadrupole, ion trap (IT), Fourier transform ion cyclotron resonance (FTICR) and
      time-of-flight (TOF) mass spectrometers are used as on-line analyzer. The
      relationship between structural features and fragmentation patterns should be
      investigated as thoroughly as possible and hence be applied in the on-line
      analysis to deduce the structures of detected peaks. Characteristic fragmentation
      behaviors of the reference standards, as well as information regarding polarity
      obtained from retention time data, on-line UV spectra, data from the literature
      and bio-sources of the compounds allowed the identification of the phytochemical
      constituents in the crude extracts. Although a mass spectrometer is not a
      universal detector, high-performance liquid chromatography coupled with
      multistage mass spectrometry (HPLC-MS(n)) technique was still proved to be a
      rapid and sensitive method to analyze the majority of the many constituents in
      herbal medicines, particularly for the detection of those present in minor or
      trace amounts. The methods established using HPLC-MS techniques facilitate the
      convenient and rapid quality control of traditional medicines and their
      pharmaceutical preparations. However, the quantitative analysis is not the topic
      of this review.

PMID- 18804770
TI  - Optimization of two-dimensional gradient liquid chromatography separations.
AB  - An almost orthogonal comprehensive two-dimensional liquid chromatography was
      developed for the separation of phenolic and flavone natural antioxidants by
      using combinations of a polyethylene glycol silica micro-column in the first
      dimension and a porous-shell fused-core C18 column in the second dimension, both
      in the reversed-phase mode. System orthogonality was improved using parallel
      gradients of acetonitrile in buffered mobile phase. A new approach was proposed
      to optimize matching segmented gradient profiles in the two dimensions. An
      algorithm was developed for automatic corrections of the shifts in retention in
      the second dimension induced by the parallel two-dimensional gradient operation
      technique. Using the porous-shell C18 column in the second dimension at elevated
      temperature (60 degrees C) and high pressure (480 bar) with optimized segmented
      profiles of the parallel gradients in the two dimensions, the overall separation
      time for comprehensive LC x LC was reduced to 30 min.

PMID- 18804771
TI  - New multiresidue method using solid-phase extraction and gas chromatography-micro
      electron-capture detection for pesticide residues analysis in royal jelly.
AB  - Royal jelly, one of the most important bee products, can be contaminated with
      pesticide and/or antibiotic residues resulting from treatments applied either
      inside beehives or in the agricultural environment. A new multiresidue method was
      developed and validated for analysis of nine pesticides in royal jelly. Solid
      phase extraction RP-C(18) cartridges were used for sample purification and
      isolation of analytes. Final solution was analyzed with GC and micro-electron
      capture detection. Four synthetic acaricides used by beekeepers (bromopropylate,
      coumaphos, malathion and tau-fluvalinate), and moreover one pyrethroid, two
      organochlorine, and two organophosphate insecticides were tested. Linearity is
      demonstrated for the range of 0.0025-1mgkg(-1), with correlation coefficients
      ranging from 0.99991 to 0.99846, depending on the analyte. Overall recovery rates
      from royal jelly blank samples spiked at five fortification levels ranged from
      80.8% (lindane) to 91.3% (ethion), well above the range defined by the
      SANCO/10232/2006 and EC/675/2002 documents. The limit of quantification was
      <0.003-0.005 mg kg(-1) depending on the analyte, and the reporting level of the
      method, defined as the lowest recovery level, was 0.005 mg kg(-1).

PMID- 18804772
TI  - Multi-class determination of antimicrobials in meat by pressurized liquid
      extraction and liquid chromatography-tandem mass spectrometry.
AB  - A multi-residue method using pressurized liquid extraction (PLE) and liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) has been developed for
      determining trace levels of 31 antimicrobials, including beta-lactams,
      lincosamides, macrolides, quinolones, sulfonamides, tetracyclines,
      nitroimidazoles and trimethoprim. The extraction method required pre
      homogeneization of the meat with EDTA-washed sand and subsequent one-static-cycle
      extraction for 10 min with 40 ml of water at 1500 psi and 70 degrees C. The
      effect of operation temperature, pressure, flush volume, and static cycles on PLE
      performance was studied. Average recoveries ranged from 75 to 99% with relative
      standard deviations <18%. The method was validated according to the European
      Union requirements (2002/657/EC). In addition to the quality parameters included
      in that decision, the limits of detection (LODs) and quantification (LOQs) were
      determined. The use of LC-MS/MS provided LODs (between 3 and 15 microg kg(-1))
      and LOQs (between 10 and 50 microg kg(-1)), by far lower than half of their
      maximum residue limits (MRLs) (between 50 and 1200 microg kg(-1)). Confirmation
      of the presence of any of the studied compounds was accomplished in 1h after
      sample receipt. This methodology has been successfully applied to the analysis of
      cattle and pig tissue samples from local markets and slaughterhouses of the
      Valencian Community (Spain). The results showed the presence of some
      antimicrobials at different concentrations. Quinolones and tetracyclines were the
      antimicrobials most detected in cattle and pig samples, respectively.
      Sulfonamides were also frequently detected in both types of samples.

PMID- 18804773
TI  - Determination of arylamines and aminopyridines in pharmaceutical products using
      in-situ derivatization and liquid chromatography-mass spectrometry.
AB  - Arylamines and aminopyridines form a class of potentially genotoxic impurities
      (PGIs) that can be present at trace levels in active pharmaceutical ingredients
      (APIs). A generic method was developed that allows the analysis of a selected set
      of these solutes at sub-ppm level relative to the drug substance. A highly
      concentrated solution of the pharmaceutical compound is analyzed by LC-MS using a
      single quadrupole mass spectrometer in the selected ion monitoring (SIM) mode.
      Since a number of target compounds show little or no retention in the reversed
      phase LC setup, a fast and simple derivatization procedure using
      hexylchloroformate was applied. The amide derivatives of the PGI result in a
      higher molecular weight (more specific ion for SIM) and better chromatographic
      behavior. The methodology, consisting of a dual run on respectively a non
      derivatized and a derivatized sample, was validated and applied to a selection of
      pharmaceutical substances. The method was found to be sufficiently sensitive and
      robust and is applicable in a QA/QC environment.

PMID- 18804774
TI  - One-step purification of palmatine and its derivative dl-tetrahydropalmatine from
      Enantia chlorantha using high-performance displacement chromatography.
AB  - Palmatine and its reduced form, dl-tetrahydropalmatine are a group of
      isoquinoline alkaloids that have been reported to display a variety of biological
      and pharmacological activities. Both drugs are hydrophilic and are difficult to
      be purified by conventional purification methods of natural products. A high
      performance displacement chromatography (HPDC) method successfully purified
      palmatine and its semi-synthetic derivative dl-tetrahydropalmatine from crude
      extract of the African medicinal plant Enantia chlorantha. The crude extract from
      the root bark of E. chlorantha was fractionated on an analytical reversed-phase
      C(18) column by using 0.1% trifluoroacetic acid (TFA) or acetic acid/H2O as a
      carrier and cetylpyridinium trifluoroacetate (or acetate) (1.9mg/mL) in 0.1% TFA
      (or acetic acid)/H2O as a displacer. Palmatine was quantitatively purified at
      >98% purity in the fully developed displacement mode. dl-Tetrahydropalmatine was
      semi-synthesized by NaBH4 reduction from crude palmatine and directly purified by
      HPDC. Both palmatine and dl-tetrahydropalmatine were identified by high
      resolution electrospray tandem mass spectrometry, (1)H NMR and (13)C NMR. This is
      the first report of one-step HPDC purification of natural and semi-synthetic
      products from a complex crude extract.

PMID- 18804775
TI  - The use of dielectric spectroscopy for the characterization of polymer-induced
      flocculation of polystyrene particles.
AB  - The flocculation of colloidal suspensions is an important unit operation in many
      industries, as it greatly improves the performance of solid separation processes.
      The number of available techniques for evaluating flocculation processes on line
      is limited, and most of these are only functional in dilute suspensions. Thus,
      techniques usable for flocculation characterization in high-solids suspensions
      are desirable. This study investigates the use of dielectric spectroscopy to
      monitor the flocculation of polystyrene particles with a cationic polymer. The
      frequency-dependent permittivity is modeled and the model parameters are used to
      describe the particle aggregation. The results show a peak in the modeled time
      constants of the dielectric relaxation at the onset of flocculation. Further, the
      adsorption of polymeric flocculant onto the particle surface results in a
      reduction in particle charge, evident as a decrease in the magnitude of the
      dielectric dispersion. The use of dielectric spectroscopy is found to be valuable
      for assessing flocculation processes in high-solids suspensions, as changes in
      parameters such as floc size and charge can be detected.

PMID- 18804776
TI  - Transient aging of a liquid-gas interface stretched by standing waves: on the
      interplay of chemical kinetics.
AB  - This article discusses the aging of a liquid surface enriched with surface active
      species and suddenly perturbed by standing capillary waves. Special attention is
      paid to deriving an accurate initial condition of the surface elevation. Due to
      the arising of the waves, the sub-phase and surface concentrations, C and Gamma,
      which were initially uniform and controlled by thermodynamic equilibrium, are
      modified by a transient oscillatory regime. A complete analytical description of
      the time-dependent carrier wave and oscillating chemical modulations associated
      with these concentrations is proposed for: (1) a small surface elevation, (2) a
      weak coupling with momentum transport, (3) but a strong coupling between all
      chemical transport phenomena which might be involved during transient regime:
      surface adsorption/desorption, 3-D diffusion within the sub-phase as well as near
      the liquid surface, and 2-D chemical diffusion along the surface. Analytical
      expressions resulting from regular perturbation series are compared to the limit
      aging regimes most commonly invoked in the literature, namely, diffusion- or
      sorption-limited surface aging. Finally, the (surface) compositional elasticity
      due to the arising of surface tension gradients is derived.

PMID- 18804777
TI  - Aggregation and gelation in hydroxypropylmethyl cellulose aqueous solutions.
AB  - In this work we present an analysis of the thermal behavior of
      hydroxypropylmethyl cellulose aqueous solutions, from room temperature to higher
      temperatures, above gelation. We focus on significant aspects, essentially
      overlooked in previous work, such as the correlation between polymer
      hydrophobicity and rheological behavior, and the shear effect on thermal
      gelation. Micropolarity and aggregation of the polymer chains were monitored by
      both UV/vis and fluorescence spectroscopic techniques, along with polarized light
      microscopy. Gel formation upon heating was investigated using rheological
      experiments, with both large strain (rotational) tests at different shear rates
      and small strain (oscillatory) tests. The present observations allow us to
      compose a picture of the evolution of the system upon heating: firstly, polymer
      reptation increases due to thermal motion, which leads to a weaker network.
      Secondly, above 55 degrees C, the polymer chains become more hydrophobic and
      polymer clusters start to form. Finally, the number of physical crosslinks
      between polymer clusters and the respective lifetimes increase and a three
      dimensional network is formed. This network is drastically affected if higher
      shear rates, at non-Newtonian regimes, are applied to the system.

PMID- 18804778
TI  - Surfactant mediated synthesis of spherical binary oxides photocatalytic with
      enhanced activity in visible light.
AB  - Spherical silica and zirconia mixed titania and pure titania samples were
      prepared in presence of cetyltrimethylammonium bromide (CTAB) through controlled
      hydrolysis of corresponding metal alcoxides. Effect of surfactant amount and
      calcinations temperature on morphology, surface area and photocatalytic activity
      is studied using PXRD, SEM, FTIR, Solid state UV-vis spectroscopy and BET surface
      area. It is well observed that in presence of 2 mol% CTAB, uniform sized
      spherical oxide particles can be synthesized. However, increasing or decreasing
      the surfactant amount does not favor the spherical particle formation. Material
      synthesis in presence of CTAB not only helps in the spherical particle formation
      but also increases the surface area and visible light absorption. Studies on
      photocatalytic lead removal with respect to calcination temperature indicate that
      the calcination at 500 degrees C is most suitable for the best photocatalytic
      activity. Mixing of zirconia and silica helps in anatase phase stabilization even
      at 900 degrees C calcination. Accordingly low decrease in surface area even at
      900 degrees C calcination is observed. Due to the phase stabilization and higher
      surface area binary oxide materials showed comparatively better photocatalytic
      activity even after calcination at 900 degrees C. So it can be concluded that
      present synthesis approach can produce uniform sized spherical binary oxide
      materials with better photocatalytic activity in visible light.

PMID- 18804780
TI  - Synthesis, characterization of mono, di and tri alkyl surfactant intercalated
      Wyoming montmorillonite for the removal of phenol from aqueous systems.
AB  - Organoclays were synthesized by the ion exchange of cationic surfactants
      containing single, double and triple alkyl chains for sodium ions in an aqueous
      suspension of Wyoming Na-montmorillonite. The characterization of organoclays
      with and without adsorbed phenol was determined by X-ray diffraction, TEM and
      thermal analysis. Differences in the surfaces and in the interlayer of the mono,
      di and tri alkyl chain organoclays resulted in differences in the adsorption
      efficiency for phenol with tri > di > mono >> Na-Mt. The results prove that
      organoclays can be effective for the removal of phenol from an aqueous solution
      and this removal is a function of the surfactant molecule and its concentration.
      In general, the higher the concentration as measured by the CEC value and the
      greater the number of alkyl chains in the surfactant molecule, the greater the
      percentage of the phenol that is removed.

PMID- 18804779
TI  - Glucose-responsive microgels with a core-shell structure.
AB  - New multiresponsive core-shell microgels have been synthesized, with a
      thermoresponsive core and a glucose-responsive shell, made respectively of poly(N
      isopropylacrylamide) (pNIPAM) and pNIPAM-co-acrylamidophenylboronic acid (pNIPAM
      co-APBA). The structure of the particles was elucidated by means of dynamic light
      scattering. Their thermal properties were investigated and compared to those of
      the core alone. Without glucose, the hydrophobic shell prevented the core from
      swelling in a certain temperature range where the shell was shown to be
      collapsed. This core compression vanished upon glucose addition, when the shell
      became hydrophilic and swelled. Therefore, the extent of core swelling was
      regulated by two processes: its own internal stimulus, i.e. temperature, and
      shell compression, which is proportional to glucose concentration, even at
      physiological salinity. The concept was applied to a selected chemical
      composition. Core-shell microgels with a response to glucose at physiological pH
      were obtained and used to encapsulate insulin. Insulin release was shown to be
      regulated by the presence of glucose.

PMID- 18804781
TI  - Measurement of surface potential at silver chloride aqueous interface with single
      crystal AgCl electrode.
AB  - The surface potential at the silver chloride aqueous interface was measured by
      means of a single-crystal silver chloride electrode (SCr-AgCl). The measurements
      were conducted by titration of the KCl solution with AgNO3, and vice versa. The
      SCr-AgCl electrode potentials were converted to surface potentials psi(0) by
      setting zero at the point of zero charge at pCl = 5.2. The psi(0)(pCl) function
      was linear, with a slope 12% lower with respect to the Nernst equation. It was
      demonstrated that the surface potential at the silver halide aqueous interface
      could be interpreted by means of the surface complexation model, originally
      developed for metal oxides.

PMID- 18804782
TI  - A novel preparation of surface-modified paramagnetic magnetite/polystyrene
      nanocomposite microspheres by radiation-induced miniemulsion polymerization.
AB  - A novel and facile approach to the preparation of paramagnetic
      magnetite/polystyrene nanocomposite microspheres by 60Co gamma-ray radiation
      induced miniemulsion polymerization is reported. First, we modified the magnetite
      nanoparticles (MPs) with a Y-shaped surfactant: 12-hexanoyloxy-9-octadecenoic
      acid (HOA). Nanocomposite microspheres consisting of polystyrene-iron oxide
      nanoparticles then were prepared by the radiation-induced miniemulsion
      polymerization of styrene in the presence of HOA-modified MPs using HOA as
      stabilizer. The final products were characterized by X-ray powder diffraction
      (XRD), Fourier transform infrared spectroscopy (FT-IR), field-emission scanning
      electron microscopy (FESEM), thermogravimetric analysis (TGA), and X-ray
      photoelectron spectroscopy (XPS). The effects of the dose rate, the amounts of
      added hexadecane (HD) and MPs, and the morphology of the final products were
      studied. We have also studied the polymerization kinetics to prove the
      miniemulsion polymerization mechanism of the nanocomposite microspheres.

PMID- 18804783
TI  - In search of the best method to predict acute coronary syndrome using only the
      electrocardiogram from the emergency department.
AB  - INTRODUCTION: The aim of this study was to compare different methods to predict
      acute coronary syndrome (ACS) using only data from a single electrocardiogram
      (ECG) in the emergency department (ED). METHOD: We compared the ACS prediction
      abilities of classical ECG criteria, human expert ECG interpretation, a logistic
      regression model and an artificial neural network ensemble (ANN). The ED ECG and
      discharge diagnoses were retrieved for 861 patient visits to the ED for chest
      pain. Cross-validation was used to estimate the generalization performance of the
      logistic regression and the ANN model. RESULTS: The logistic regression model had
      the overall best performance in predicting ACS with an area under the receiver
      operating characteristic curve of 0.88. The sensitivities of logistic regression,
      ANN, expert physicians, and classical ECG criteria were 95%, 95%, 82%, and 75%,
      respectively, and the specificities were 54%, 44%, 63%, and 69%. CONCLUSION: Our
      logistic regression model was the best overall method to predict ACS, followed by
      our ANN. Decision support models have the potential to improve even experienced
      ECG readers' ability to predict ACS in the ED.

PMID- 18804784
TI  - Diagnosis and characterization of left ventricular hypertrophy by computerized
      acoustic cardiography, brain natriuretic peptide, and electrocardiography.
AB  - BACKGROUND: Using echocardiography as the gold standard to diagnose and classify
      subtypes of left ventricular hypertrophy (LVH), we compared the diagnostic
      accuracy of computerized acoustic cardiography, brain natriuretic peptide (BNP),
      and the Cornell voltage criteria. METHODS: Three hundred fifty-two patients with
      suspected heart failure had contemporaneous BNP sampling, 12-lead
      electrocardiography, computerized acoustic cardiography, and echocardiography.
      Left ventricular hypertrophy was classified as eccentric vs concentric based on
      echocardiographic relative wall thickness. Computerized acoustic cardiography was
      used to measure acoustic and automated electrical parameters. RESULTS: Of all
      models, BNP combined with either computerized acoustic cardiography (c-statistic,
      0.78; 95% confidence interval [CI], 0.74-0.78) or Cornell voltage (c-statistic,
      0.76; 95% CI, 0.71-0.81) had the best diagnostic performance for LVH detection.
      For LVH characterization, the computerized acoustic cardiography model
      outperformed other models (c-statistic, 0.73; 95% CI, 0.66-0.80). CONCLUSIONS:
      Brain natriuretic peptide combined with either computerized acoustic cardiography
      or Cornell voltage had the highest diagnostic accuracy for the detection of LVH,
      compared to Cornell voltage, BNP, or computerized acoustic cardiography alone.
      Computerized acoustic cardiography outperformed other models for the
      characterization of LVH subtypes.

PMID- 18804785
TI  - Study of repolarization heterogeneity and electrocardiographic morphology with a
      modeling approach.
AB  - BACKGROUND: Increase of heart repolarization heterogeneity has been linked to
      severe or even life-threatening arrhythmia like torsades de pointes and other
      forms of ventricular tachycardia. Although electrocardiography (ECG) still
      remains as the most convenient and cost-effective method of monitoring electrical
      activity of the heart, the link between ECG morphology and repolarization
      heterogeneity is not clear. Previous attempts of using QT interval dispersion
      from multiple leads to assess the heterogeneity changes were not successful
      either. METHOD: The aim of this study is to use a cell-to-ECG model to study ECG
      morphology changes while varying transmural heterogeneity. The heterogeneity is
      simulated by increasing the difference of M cell Ikr block factors from either
      endocardial or epicardial cells. The model-simulated ECGs were processed and
      measured. The ECG parameters studied include QT interval dispersion of standard
      12-lead ECG, QT peak dispersion, and T-peak to T-end interval (TpTe). An ECG
      vector magnitude signal based on 12-lead ECG was formed to estimate the global QT
      interval (vs lead-by-lead QT interval used for calculating QT dispersion) and
      also the global TpTe (TpTe_VM). RESULTS: The results based on the model
      simulation show that the TpTe_VM is highly correlated with transmural dispersion
      of repolarization (TDR), with a correlation coefficient of 0.97. The correlation
      coefficients of QT interval dispersion and QT peak dispersion with TDR are 0.44
      and 0.80, respectively. CONCLUSION: In conclusion, the cell-to-ECG model provides
      a unique way to study electrophysiology and to link physiologic factors to ECG
      morphology changes. The simulation results suggest that global TpTe can be a
      strong indicator of TDR.

PMID- 18804786
TI  - The relationship between programmed pacemaker pulse amplitude and the surface
      electrocardiogram recorded amplitude: application of a new high-bandwidth
      electrocardiogram system.
AB  - BACKGROUND: Recording and displaying outputs from electronic pacemakers with
      electrocardiogram (ECG) recorders typically used in clinical practice have
      presented a number of technical limitations. We have recently reported on a new
      high-bandwidth ECG system and have shown that it is capable of reproducing
      accurate pulse amplitudes and durations from the body surface. In the present
      work, we have used our data to calculate a transform function between the
      programmed pacemaker output voltage and the amplitude on the body surface.
      METHODS: We recorded 3 high-bandwidth (75,000 samples per second) ECGs from each
      of 100 pacemaker patients at 3 different programmed outputs. Each pacemaker pulse
      was isolated using the criterion standard annotations, and the pulses were
      transformed from the 8 independent leads to an XYZ vector using the Dower
      transform. The magnitude of the vector was calculated. Linear regression
      techniques were used to learn a transfer function over the records of the first
      50 patients. These results were tested against the second 50 patients. RESULTS:
      The measured pacemaker pulse vector magnitude has a linear relationship to the
      programmed pacemaker amplitude on a per-patient basis for most of the patients in
      the training database. The linear transform models were tested against the
      testing set with an R(2) metric of 0.38 for the atrial pulses and 0.54 for the
      right ventricular pulses. CONCLUSION: Understanding the relationship between the
      generated pacemaker pulses and the measurements at the body surface will help
      drive specifications for pacemaker pulse detection among the various device
      manufactures.

PMID- 18804787
TI  - New descriptors of T-wave morphology are independent of heart rate.
AB  - T-wave morphology descriptors are sensitive to drug-induced changes and may be a
      useful addition to the QT interval in cardiac safety trials. Intrasubject heart
      rate dependence of T-wave morphology was investigated in a sample of 39 healthy
      individuals. Ten-second electrocardiograms were obtained from daytime Holter
      recordings. Duration parameters (QT, ToTe, TpTe, and others), a number of basic T
      wave morphology parameters (amplitude, area, and others) as well as advanced
      morphology descriptors (asymmetry, flatness, and others) were measured
      automatically. Heart rate dependence was examined by means of analysis of
      covariance. The results showed clear heart rate dependence for the QT interval
      (R(2) = 0.53-0.57) and a moderate degree of heart rate dependence for the basic
      morphology parameters (amplitude, area, and others) (R(2) = 0.17-0.42). Both the
      advanced T-wave descriptors (asymmetry, flatness, and others), ToTe intervals and
      TpTe intervals, were practically independent of heart rate (R(2) = 0-0.08),
      making heart rate correction unnecessary for these parameters.

PMID- 18804788
TI  - Low QRS voltage and its causes.
AB  - Electrocardiographic low QRS voltage (LQRSV) has many causes, which can be
      differentiated into those due to the heart's generated potentials (cardiac) and
      those due to influences of the passive body volume conductor (extracardiac).
      Peripheral edema of any conceivable etiology induces reversible LQRSV, reduces
      the amplitude of the P waves and T waves, decreases the duration of P waves, QRS
      complexes, and QT intervals, and alters in turn the measurements of the signal
      averaged electrocardiogram and T wave alternans, all with enormous clinical
      implications.

PMID- 18804789
TI  - Cardiac repolarization instability during normal postnatal development.
AB  - Long QT syndrome is a disease characterized by abnormal lengthening of the QT
      interval and by sudden cardiac death. It is a disease of development, with the
      incidence of a sudden event increasing during childhood. Repolarization
      instability during postnatal development could make the substrate susceptible to
      a fatal arrhythmia. Dynamic changes in repolarization that occur on a beat-to
      beat basis, known as alternans, are a hallmark of electrical instability. T-wave
      alternans (TWA) in the electrocardiogram correlates with arrhythmia risk and long
      term survival in adults. We determined TWA properties longitudinally in vivo in 7
      propofol-sedated New Zealand white rabbits using transesophageal pacing weekly
      from 2 to 10 weeks of age. Furthermore, TWA induction after the onset of rapid
      pacing was characterized in vitro in 6 infant (2 weeks) and 6 adolescent (7
      weeks) isolated, arterially perfused rabbit hearts. In vivo, TWA amplitude was
      maximum at 2 weeks and declined with age. Isoproterenol increased TWA at 8 weeks
      (adolescence). In vitro, large-amplitude TWA was induced with rapid pacing in
      both infant and adolescents but decreased to low, steady-state levels in infants.
      We conclude that TWA properties are age dependent in rabbit. Significant TWA is
      induced in rabbit at the onset of rapid pacing.

PMID- 18804790
TI  - Significant clinical improvement in radiation-induced lumbosacral
      polyradiculopathy by a treatment combining pentoxifylline, tocopherol, and
      clodronate (Pentoclo).
AB  - Radiation-induced (RI) peripheral neuropathy is a rare and severe delayed
      complication of radiotherapy that is spontaneously irreversible, with no standard
      of treatment. We previously developed a successful antioxidant treatment in RI
      fibrosis and necrosis. Two patients with progressive worsening RI lumbosacral
      polyradiculopathy experienced over several years a significant clinical
      improvement in their neurological sensorimotor symptoms with long-term
      pentoxifylline-tocopherol-clodronate treatment, and good safety.

PMID- 18804791
TI  - The co-occurrence of serologically proven myasthenia gravis and Miller
      Fisher/Guillain Barre overlap syndrome: a case report.
AB  - The co-occurrence of myasthenia gravis (MG) and Guillain Barre syndrome (GBS) is
      uncommon with a few reported cases in the literature. There is only one reported
      case of MG and Miller Fisher variant of GBS. We described an 84 year old Chinese
      woman with underlying seropositive myasthenia gravis (MG) who presented with
      ophthalmoplegia, areflexia and acute neuromuscular weakness. She was proved to
      have co-occurrence of MG and GBS/Miller Fisher overlap syndrome with positive
      anti-GQ1b antibody. The unusual finding in this patient raises an interesting
      question on their pathogenesis with the possibility that prior activation of the
      immune system may predispose the development of autoantibodies against other
      antigens within the same set of muscles.

PMID- 18804792
TI  - Carcinoid tumor of the kidney.

PMID- 18804795
TI  - Predicting irreparable renal ischemic injury using a real-time marker in the
      porcine model.
AB  - PURPOSE: We determined the maximal renal tolerance of warm ischemia using renal
      cortical interstitial metabolic changes to identify a potential real-time marker
      of irreparable renal function. MATERIALS AND METHODS: Using a single kidney model
      3 groups of 5 pigs each underwent 120, 150 and 180 minutes of warm ischemia,
      respectively. Microdialysis samples were collected before, during and after
      ischemia. Renal function assessments consisting of serum creatinine and GFR
      measurements were performed before ischemia and on post-ischemia days 1, 5, 9, 14
      and 28. Kidneys exposed and not exposed to ischemia were collected for
      histological study. RESULTS: Interstitial glucose and pyruvate concentrations
      decreased, while lactate concentrations increased to stable levels during
      ischemia. Glutamate spiked at 30 minutes of ischemia and subsequently tapered,
      while glycerol increased throughout warm ischemia time. At post-ischemia day 28
      renal function returned to pre-ischemia baseline levels in the group with 120
      minutes of ischemia but did not recover to baseline in the 150 and 180-minute
      ischemic groups. Functional data correlated with histological findings. The 120
      minute maximal renal tolerance of warm ischemia correlated with a mean +/- SD
      glycerol concentration of 167 +/- 24 micromol/l. CONCLUSIONS: Interstitial
      glycerol is a real-time, renal unit specific, minimally invasive marker of renal
      function deterioration. Exposure of porcine kidneys to ischemic insults resulting
      in renal cortical interstitial glycerol concentrations higher than 167 micromol/l
      is associated with irreparable functional damage in this model.

PMID- 18804796
TI  - Prospective evaluation of health related quality of life for pediatric patients
      with ureteropelvic junction obstruction.
AB  - PURPOSE: Clinical practices are increasingly proposing health related quality of
      life measures for informed treatment decisions. Dismembered pyeloplasty is an
      accepted standard therapy for ureteropelvic junction obstruction. This study
      evaluates health related quality of life in patients with ureteropelvic junction
      obstruction undergoing pyeloplasty. Patients have perceived it helpful in
      communicating health care needs to physicians. We believe this is the first study
      to use child self and parent reports prospectively in ureteropelvic junction
      obstruction. The goals of the study were to document baseline preoperative health
      related quality of life assessments, differences between parent and child
      assessments at given intervals, differences in preoperative and postoperative
      assessments, and overall clinical outcomes. MATERIALS AND METHODS: Patients
      younger than 18 years (mean 9.1 years) with ureteropelvic junction obstruction
      were included in the study. Demographic survey and validated health related
      quality of life questionnaire (Pediatric Quality of Life Inventory 4.0) were used
      preoperatively and postoperatively. The questionnaire documented subjective
      health related quality of life (physical, social, emotional and school
      functioning, and psychosocial health). Clinical outcomes were generated following
      the office visit. Questionnaire subscales were scored with algorithms provided.
      Paired t test evaluated differences in parent and child scores of less than 0.05
      were statistically significant. Tests were 2-tailed. RESULTS: Response rate was
      100%. Preoperatively emotional functioning (81.8) and psychosocial health (80.9)
      child scores were significantly higher than parent scores (70.7 and 73.9,
      respectively). Overall child score of the study population (80.9) was similar to
      that of healthy children (85). However, parent scores of physical functioning
      (78.3), psychosocial health (73.9), emotional functioning (70.7) and school
      functioning (65.5) were significantly lower than the general population. At
      postoperative week 6 child emotional functioning (91.7) and physical functioning
      (90.3) showed significant improvement (p <0.05). Parent scores of physical
      functioning (88.4), psychosocial health (82.2) and emotional functioning (80.8)
      were also significantly higher than preoperative scores. Longer followup
      demonstrated that child scores of physical functioning (96.9), psychosocial
      health (96.5), emotional functioning (95.4) and social functioning (97.1) were
      significantly higher than preoperatively. Postoperatively parents reported
      significantly higher health related quality of life scores compared to
      preoperative scores. There was no significant difference at 6 months between
      parent and child scores. Clinically all patients did well following pyeloplasty.
      CONCLUSIONS: Preoperatively children recorded higher health related quality of
      life than parents/guardians. At postoperative week 6 children and parents
      recorded higher health related quality of life compared to preoperative scores.
      At 6 months overall child health related quality of life was significantly higher
      than preoperative reports, and no significant difference was seen between parent
      and child scores. Health related quality of life evaluations enabled us to
      monitor patient recovery and progress postoperatively. Prospective evaluations at
      regular intervals helped us to document improvement in overall quality of life in
      these children.

PMID- 18804797
TI  - Re: Antibiotic prophylaxis for the prevention of recurrent urinary tract
      infection in children with low grade vesicoureteral reflux: results from a
      prospective randomized study: G. Roussey-Kesler, V. Gadjos, N. Idres, B. Horen,
      L. Ichay, M. D. Leclair, F. Raymond, A. Grellier, I. Hazart, L. De parscau, R.
      Salomon, G. Champion, V. Leroy, V. Guigonis, D. Siret, J. B. Palcoux,S. Taque, A.
      Lemoigne, J. M. Nguyen and C. Guyot. J Urol 2008; 179: 674-679.

PMID- 18804798
TI  - Acute loin pain-the danger of self-catheterization.

PMID- 18804799
TI  - Re: Influence of local tumor control on distant metastases and cancer related
      mortality after external beam radiotherapy for prostate cancer: M. J. Zelefsky,
      V. E. Reuter, Z. Fuks, P. Scardino and A. Shippy. J Urol 2008; 179: 1368-1373.

PMID- 18804800
TI  - The beneficial effect of coenzyme Q10 and lipoic acid on obstructive bladder
      dysfunction in the rabbit.
AB  - PURPOSE: Recent evidence indicates that ischemia and reperfusion are major
      etiological factors in the bladder dysfunction that occurs after partial bladder
      outlet obstruction. Coenzyme Q10 and alpha-lipoic acid are found naturally in
      mitochondria and act as potent antioxidants. We investigated the beneficial
      effects of coenzyme Q10 plus alpha-lipoic acid in a rabbit model of bladder
      outlet obstruction. MATERIALS AND METHODS: Twenty male rabbits were divided into
      5 groups. Group 1 served as control and group 2 received three weeks of coenzyme
      Q10 plus alpha-lipoic acid supplementation. Rabbits in group 3 underwent surgical
      partial bladder outlet obstruction for duration of four weeks and groups 4 and 5
      were obstructed for seven weeks. In group 5, coenzyme Q10 plus alpha-lipoic acid
      supplementation was given following 4 weeks obstruction and continued till the
      end of the seven weeks. The contractile responses to various agents were
      determined. The protein nitration and carbonylation levels were studied by
      immunoblotting. Nerve function was determined by choline acetyltransferase
      activity and nerve density. RESULTS: The contractile responses to different forms
      of stimulations, including field stimulation, ATP, carbachol and KCl all showed
      decreases following 4 and 7 weeks obstruction. Treatment with coenzyme Q10 plus
      alpha-lipoic acid significantly restored contractile responses to all forms of
      stimulation. Treatment also had mitochondrial and neuronal effects and reduced
      protein nitration and carbonylation. Histologically there was less detrusor
      muscle hypertrophy. CONCLUSIONS: The current study clearly demonstrates that
      coenzyme Q10 and alpha-lipoic acid supplementation can improve bladder function
      after outlet obstruction.

PMID- 18804801
TI  - The role of vesicoureteral reflux in acute renal cortical scintigraphic lesion
      and ultimate scar formation.
AB  - PURPOSE: We assessed whether differences exist in the rates of acute photon
      defect and scar formation using dimercapto-succinic acid scintigraphy according
      to the presence and grade of vesicoureteral reflux. MATERIALS AND METHODS: A
      total of 389 patients with a first febrile urinary tract infection were enrolled.
      For all patients ultrasonography, dimercapto-succinic acid scintigraphy and
      voiding cystourethrography were performed. Dimercapto-succinic acid scintigraphy
      was performed within 5 days of and 6 months after diagnosis of urinary tract
      infection. Voiding cystourethrography was performed after the acute phase of
      urinary tract infection. The rates of acute photon defect and scar formation on
      dimercapto-succinic acid scintigraphy according to the presence and grade of
      vesicoureteral reflux were assessed. RESULTS: A total of 125 females and 264
      males were included in the study. Of the patients 93 had refluxing urinary tract
      infection and 296 had nonrefluxing infection. The rate of acute photon defect
      (74.2% vs 32.1%, p = 0.0001) and the rate of ultimate scar change on followup
      dimercapto-succinic acid scintigraphy were significantly higher in patients with
      refluxing urinary tract infection (50% vs 18.3%, p = 0.0001). Positive linear
      association was noted between reflux grade and acute photon defect by linear
      association test (p = 0.002). No association was found between reflux grade and
      scar formation (p = 0.262). CONCLUSIONS: Although vesicoureteral reflux is not a
      prerequisite for development of acute photon defect and subsequent renal
      scarring, reflux itself might be an aggravating factor for acute photon defect
      and scar formation. There seems to be a correlation between reflux grade and
      frequency of acute photon defect on dimercapto-succinic acid scintigraphy but
      scar change occurs independently of reflux grade.

PMID- 18804802
TI  - Effects of long-term dietary soy treatment on female urethral morphology and
      function in ovariectomized nonhuman primates.
AB  - PURPOSE: Agonistic effects of estrogen on the female urethra include an increase
      in contractile function, blood flow and mucosal hyperplasia. Whether such effects
      can be achieved by soy based phytoestrogen diets is unclear. We studied the
      effects of chronic phytoestrogen treatment on the structural and functional
      properties of the urethra in ovariectomized monkeys. MATERIALS AND METHODS:
      Following ovariectomy 18 monkeys were fed a diet containing soy (9) or casein (9)
      based protein for 32 months. At necropsy the urethra and bladder were removed and
      the urethra was separated into 3 segments of equal length, including a proximal,
      a middle and a distal segment. Each urethral segment and 1 bladder segment was
      tested in vitro for functional responses to electrical field stimulation and
      pharmacological stimulation, and the proximal to distal segments were tested for
      urothelial thickness and mucosal area. RESULTS: Electrical field stimulation
      produced frequency dependent contractile responses in the bladder, proximal and
      middle segments but not in the distal segment. Carbachol, phenylephrine and
      endothelin-1 produced concentration dependent contractions in all urethral
      segments. The maximum response decreased from the proximal to the distal segment
      (p </=0.05). The maximum response in the proximal and bladder segments to
      pharmacological stimulation and electrical field stimulation as well as mucosal
      area and urothelial thickness were significantly higher in the treatment than in
      the control group (p < or =0.05). CONCLUSIONS: Chronic phytoestrogen treatment
      results in increased responsiveness of the proximal urethra to pharmacological
      and electrical stimulation, which is associated with an increase in urothelial
      thickness and mucosal area. This study indicates that dietary soy may have
      estrogen agonist effects on the urethra and bladder in estrogen deficient
      females.

PMID- 18804803
TI  - Re: A single instillation of epirubicin after transurethral resection of bladder
      tumors prevents only small recurrences: I. Berrum-svennung, T. Granfors, S.
      Jahnson, H. Boman and S. Holmang. J Urol 2008; 179: 101-106.

PMID- 18804806
TI  - Re: The 20-core prostate biopsy protocol--a new gold standard?: V. Ravery, S.
      Dominique, X. Panhard, M. Toublanc, L. Boccon-Gibod and L. Boccon-Gibod. J Urol
      2008; 179: 504-507.

PMID- 18804807
TI  - Microrobot assisted laparoscopic urological surgery in a canine model.
AB  - PURPOSE: Robotic technologies have had a significant impact on surgery. We report
      what is to our knowledge the first use of microrobots to perform laparoscopic
      urological surgery in a canine model. MATERIALS AND METHODS: Nonsurvival
      laparoscopic radical prostatectomy and radical nephrectomy were performed using
      microrobotic camera assistance. Following the administration of general
      anesthesia miniature camera robots were inserted in the insufflated abdomen via a
      15 mm laparoscopic port. These microrobots were mobile, controlled remotely to
      desired locations and provided views of the abdominal cavity, assisting the
      laparoscopic procedures. Additional ports and laparoscopic instruments were
      placed in the abdomen using the views provided by these microrobots. RESULTS: One
      dog underwent laparoscopic prostatectomy and another underwent laparoscopic
      nephrectomy. The 2 procedures were completed successfully. Microrobots provided
      additional views from several angles, aiding in the performance of the
      procedures. CONCLUSIONS: Miniature camera robots (microrobots) provide a mobile
      viewing platform. With added functionality these new robots have the potential to
      further evolve the robotic armamentarium for surgeons.

PMID- 18804811
TI  - The significance of monoamine oxidase-A expression in high grade prostate cancer.
AB  - PURPOSE: Gleason grade 4/5 prostate cancer is a determinant for recurrence
      following radical prostatectomy. Monoamine oxidase-A is over expressed in grade
      4/5 compared to grade 3 cancer. Monoamine oxidase-A is also expressed by normal
      basal cells and in vitro studies suggest that its function is to repress
      secretory differentiation. Therefore, monoamine oxidase-A in grade 4/5 cancer
      might reflect dedifferentiation to a basal cell-like phenotype. We investigated
      whether monoamine oxidase-A expression correlates with another basal cell
      protein, CD44, in high grade cancer and whether either is associated with an
      aggressive phenotype. MATERIALS AND METHODS: A total of 133 grade 4/5 archival
      cancers from a cohort previously used to evaluate the prognostic significance of
      histomorphological variables were scored for monoamine oxidase-A and CD44
      immunohistochemical labeling. Spearman rank correlations of the proteins, and
      histomorphological and clinical variables were determined. The univariate and
      multivariate value of each variable as a determinant of biochemical recurrence
      was assessed by logistic regression. RESULTS: Monoamine oxidase-A expression
      correlated with CD44. Neither was prognostic for biochemical recurrence. However,
      monoamine oxidase-A expression positively correlated with preoperative serum
      prostate specific antigen and the percent of grade 4/5 cancer. CONCLUSIONS:
      Concurrent expression of monoamine oxidase-A and CD44 suggests that grade 4/5
      cancer may be basal cell-like in nature, despite the absence of other classic
      basal cell biomarkers such as cytokeratins 5 and 14, and p63. The correlation of
      monoamine oxidase-A expression with prostate specific antigen and the percent of
      grade 4/5 cancer suggests that monoamine oxidase-A may contribute to growth of
      high grade cancer and that antidepressant drugs that target monoamine oxidase-A
      may have applications in treating prostate cancer.

PMID- 18804812
TI  - Effects of estrogen, raloxifene and levormeloxifene on alpha1A-adrenergic
      receptor expression.
AB  - PURPOSE: We investigated the effect of estrogen, raloxifene and levormeloxifene
      on alpha1A-adrenergic receptor expression. MATERIALS AND METHODS: Postpartum rats
      underwent intravaginal balloon injury and ovariectomy, and were then treated with
      estrogen or placebo for 8 weeks. The urethras were examined for alpha1A
      adrenergic receptor expression by Western blot analysis and immunohistochemistry.
      Urethral smooth muscle cells were isolated from untreated female rats and
      examined for the expression of estrogen receptors alpha and beta by
      immunofluorescence microscopy. Urethral smooth muscle cells were treated with
      estrogen, raloxifene or levormeloxifene for 24 hours and examined for alpha1A
      adrenergic receptor expression by real-time polymerase chain reaction. The
      effects of these drugs on alpha1A-adrenergic receptor expression were further
      examined by promoter assays. RESULTS: Estrogen treatment resulted in decreased
      alpha1A-adrenergic receptor expression in the urethras. Urethral smooth muscle
      cells expressed estrogen receptors alpha and beta, the former predominantly in
      the cytoplasm and the latter in the nucleus. Estrogen significantly down
      regulated alpha1A-adrenergic receptor mRNA expression, while raloxifene and
      levormeloxifene had no significant effect. Estrogen also significantly down
      regulated alpha1A-adrenergic receptor promoter in the presence of estrogen
      receptor alpha or beta. Raloxifene and levormeloxifene up-regulated alpha1A
      adrenergic receptor promoter in the presence of estrogen receptor alpha but not
      beta. CONCLUSIONS: Estrogen down-regulated alpha1A-adrenergic receptor expression
      in the urethral smooth muscle of female rats, while raloxifene and
      levormeloxifene had no significant effect. These findings represent a possible
      molecular mechanism through which estrogen, raloxifene and levormeloxifene
      differentially affect urinary continence.

PMID- 18804813
TI  - Genomic variants of ATF3 in patients with hypospadias.
AB  - PURPOSE: ATF3, an estrogen responsive gene expressed during genital development,
      could be implicated in the etiology of hypospadias. ATF3 is up-regulated in the
      foreskin of patients with hypospadias and is implicated in suppression of the
      cell cycle, which may interfere with urethral cell growth. We sought to
      investigate the sequence of ATF3 in patients with hypospadias. MATERIAL AND
      METHODS: Direct sequencing of coding exons and splice sites of ATF3 was performed
      in 41 boys with hypospadias and 30 controls. In addition, ATF3 expression in 1
      human fetal penis with and 1 without hypospadias was studied by
      immunohistochemical analysis. RESULTS: A missense variant (L23M) was identified
      in a boy with anterior hypospadias. This amino acid is highly conserved. Three
      genomic variants (C53070T, C53632A, Ins53943A) were found in or close to exon 6
      in patients with perineal, penoscrotal and anterior hypospadias. This important
      exon includes splice sites for an alternative transcript (ATF3DeltaZip) that have
      been implicated in regulation of the function of ATF3. None of these genomic
      variants was present in controls. Immunochemical analysis revealed that in normal
      fetuses ATF3 is not expressed in and around the urethra, while in patients with
      hypospadias ATF3 is over expressed in the urethral plate and subcutaneous tissue,
      especially around the ectopic orifice of the urethra. CONCLUSIONS: Genomic
      variants of ATF3 are present in 10% of our patients with hypospadias. We also
      report an abnormal expression pattern of ATF3 in a hypospadiac fetus. The direct
      implication of ATF3 in the occurrence of hypospadias remains to be confirmed by
      functional studies of the genomic variants we describe.

PMID- 18804814
TI  - Disrupting the interaction between HOX and PBX causes necrotic and apoptotic cell
      death in the renal cancer lines CaKi-2 and 769-P.
AB  - PURPOSE: The HOX genes are a family of homeodomain containing transcription
      factors that determine embryonic tissue identity and also have regulatory and
      oncogenic roles in adult cells. We quantified the expression of HOX genes in
      normal kidney tissue, primary tumors and derived cell lines, and examined their
      role in renal cancer cell survival. MATERIALS AND METHODS: Quantitative
      polymerase chain reaction was used to evaluate HOX gene expression in cells and
      tissues. HOX gene function was disrupted using a peptide that blocks the
      interaction between HOX proteins and their PBX cofactor. Apoptosis was assessed
      by annexin/propidium iodide staining and direct measurement of caspase activity.
      RESULTS: Primary renal tumors and derived cell lines showed abnormal HOX gene
      expression. Furthermore, blocking HOX activity by targeting the interaction
      between HOX and its cofactor PBX caused apoptotic and necrotic cell death in the
      renal cancer cell lines CaKi-2 and 769-P, while sparing normal adult kidney
      cells. CONCLUSIONS: Our findings suggest that the HOX/PBX dimer is a potential
      therapeutic target in renal cancer.

PMID- 18804815
TI  - Atorvastatin inhibits renal crystal retention in a rat stone forming model.
AB  - PURPOSE: The interactions between crystals and renal tubular cells are important
      factors in urolithiasis formation. Moreover, some reports have suggested the
      involvement of renal tubular cell injury in crystal-cell interaction processes.
      Atorvastatin, which is a competitive inhibitor of 3-hydroxy-3-methylglutaryl
      coenzyme A, is prescribed to decrease high cholesterol levels, and it has anti
      inflammation and anti-oxidization activities. Atorvastatin is also reported to
      control transforming growth factor-beta1 expression. We investigated whether
      atorvastatin can prevent renal tubular cell injury by oxalate and inhibit renal
      crystal retention. MATERIALS AND METHODS: Ten-week-old specific pathogen-free
      male Sprague-Dawley rats were used. Atorvastatin (2 mg/kg) in 0.5% carboxymethyl
      cellulose was administered orally daily for 2 weeks. The rats were separated into
      4 experimental groups, including group 1--water and 0.5% carboxymethyl cellulose
      daily, group 2--water and atorvastatin in 0.5% carboxymethyl cellulose daily,
      group 3--1% ethylene glycol dissolved in water, 0.5 mug vitamin D3 dissolved in 1
      ml salad oil and 0.5% carboxymethyl cellulose daily, and group 4--1% ethylene
      glycol dissolved in water, 0.5 microg vitamin D3 dissolved in 1 ml salad oil and
      atorvastatin in 0.5% carboxymethyl cellulose daily. The ethylene glycol model of
      hyperoxaluria and the effect of atorvastatin treatment were analyzed in groups 1
      to 4. Urine samples were collected every 24 hours in metabolic cages and analyzed
      immediately or stored at -70C until analysis. The rats were sacrificed after 2
      weeks and the kidneys were removed for further examination. We measured urinary N
      acetyl glucosaminidase levels as a biomarker of renal tubular cell injury and
      urinary 8-OHdG as a biomarker of oxidative stress in 24-hour urine samples.
      Removed kidneys were used for quantitative analysis of the superoxide dismutase
      level and the detection of apoptosis. Finally, we measured the amount of crystal
      deposits in renal tubular cells. RESULTS: Urinary N-acetyl glucosaminidase and 8
      OHdG levels were decreased significantly by atorvastatin treatment in this stone
      forming rat model. Atorvastatin treatment increased the superoxide dismutase
      level and inhibited the degree of renal tubular cell N-acetyl glucosaminidase
      compared with stone forming control group 3. A decrease in renal crystal
      retention was noted when excised kidneys were evaluated following atorvastatin
      treatment. CONCLUSIONS: Atorvastatin was found to have inhibitory effects on the
      renal tubular cell injury and oxidative stress caused by oxalate and crystals.
      Atorvastatin inhibited renal crystal retention. We believe that atorvastatin
      could help prevent and treat renal crystal formation.

PMID- 18804816
TI  - The effects of bladder over distention on voiding function in kindergarteners.
AB  - PURPOSE: We report the effects of bladder over distention on pediatric voiding
      function. MATERIALS AND METHODS: We enrolled healthy kindergarten children (mean
      age 4.5 +/- 1.0 years) for 2 observations of uroflowmetry and post-void residual
      urine. Additional observations were requested if the voided volume was less than
      50% of expected bladder capacity. Post-void residual was assessed within 5
      minutes after voiding. A post-void residual of more than 20 ml is regarded as
      increased. Bladder capacity is defined as voided volume plus post-void residual
      and shown as percentage of expected bladder capacity. The uroflowmetry curves
      were categorized as bell-shaped or nonbell-shaped. RESULTS: Among 188 children
      355 observations of uroflowmetry and post-void residual were eligible for
      evaluation. Nonbell-shaped uroflowmetry curves and increased post-void residual
      were noted in 75 (21.1%) and 78 (22%) of 355 voids, respectively. Based on the
      receiver operating characteristic curve for the nonbell-shaped curves and
      increased post-void residual, bladder capacity of 115% of expected bladder
      capacity or more is defined as bladder over distention. There were statistically
      more increased post-void residuals and more nonbell-shaped uroflowmetry curves in
      the voids with bladder over distention than in those without over distention (p
      <0.01). Of the 38 children displaying both types of curves the nonbell-shaped
      curves usually occurred at a higher bladder capacity than did the bell-shaped
      curves (133% +/- 46% expected bladder capacity vs 84% +/- 38% expected bladder
      capacity, p <0.01). Peak uroflow rate increased as bladder capacity increased but
      decreased at extreme bladder over distention. CONCLUSIONS: Optimal bladder
      capacity is important for assessing pediatric voiding function. Bladder over
      distention resulted in more nonbell-shaped uroflowmetry curves and more increased
      post-void residual. At extreme over distention peak flow rate decreased as well.

PMID- 18804817
TI  - Urine derived cells are a potential source for urological tissue reconstruction.
AB  - PURPOSE: Contemporary approaches to tissue engineering and cell therapy for
      urinary tract reconstruction require invasive tissue biopsies to obtain
      autologous cells. However, these procedures are associated with potential
      complications. We determined whether the cells present in urine have
      characteristics of normal bladder cells and investigated their potential uses for
      urological reconstructive procedures. MATERIALS AND METHODS: A total of 55 urine
      samples were collected from 15 healthy individuals and 8 patients with
      vesicoureteral reflux. Urine derived cells were isolated, expanded and tested for
      progenitor and differentiated cell specific markers using flow cytometry,
      immunofluorescence and Western immunoblotting. The chromosomal stability of
      cultured urine derived cells was determined by karyotype analysis. RESULTS:
      Clones were successfully established from primary cultures of urine derived
      cells. Isolated cells showed 3 phenotypes, including fully differentiated,
      differentiating and progenitor-like cells. Some urine derived cells stained
      positive for the surface markers c-Kit, SSEA4, CD105, CD73, CD91, CD133 and CD44.
      Two to 7 cells per 100 ml urine were multipoint progenitors that could expand
      extensively in culture. Single progenitor cells had the ability to differentiate
      into the cell lineages expressing urothelial, smooth muscle, endothelial and
      interstitial cell markers. The expression of lineage markers was characterized by
      Western blot and immunofluorescence analysis. Urine derived cells also maintained
      a normal karyotype after serial culture. CONCLUSIONS: A subpopulation of cells
      isolated from urine had progenitor cell features and the potential to
      differentiate into several bladder cell lineages. Urine derived cells could serve
      as an alternative cell source for urinary tract tissue engineering and
      reconstruction.

PMID- 18804818
TI  - Re: The impact of tension-free vaginal tape on overactive bladder symptoms in
      women with stress urinary incontinence: significance of detrusor overactivity: J.
      H. Choe, M. S. Choo and K. S. Lee. J Urol 2008; 179: 214-219.

PMID- 18804820
TI  - Detubularized pedicled vaginal onlay flap urethroplasty: a new method for
      hypospadias repair of ambiguous genitalia.
AB  - PURPOSE: We introduce the detubularized pedicled vaginal onlay flap urethroplasty
      for single stage repair in ambiguous genitalia with perineoscrotal hypospadias
      and accompanying vagina, and report its preliminary surgical outcome. MATERIALS
      AND METHODS: A total of 10 children with severe perineoscrotal hypospadias and
      genital ambiguity presenting with vagina and urogenital opening underwent single
      stage reconstruction with vaginal onlay urethroplasty. Through the posterior
      sagittal or abdominoperineal approach the vagina was released and pulled out,
      with care taken to preserve its vascular pedicle. Two incisions were made along
      the lateral margins of the vagina, reaching each other on the upper surface of
      the vaginal base, converting the vagina into a longitudinal flap twice as long as
      its original length. The vagina was then trimmed and reconfigured into a suitable
      sized flap to cover the urethral plate and form a neourethra with the onlay
      technique. The onlay-tube-onlay technique was also used in 2 patients with
      insufficient urethral plate. In 5 cases severe ventral chordee was also corrected
      concurrently with free vaginal graft to the ventral corpus cavernosum without
      further dorsal plication. RESULTS: The first 3 operations using the posterior
      sagittal approach failed due to improper surgical access, and the vagina was
      discarded. However, we achieved a satisfactory outcome with no failure after
      switching to an abdominoperineal approach. Immediate postoperative and short-term
      results revealed no urethrocutaneous fistula, urethral breakdown or necrosis at
      the distal end of the neourethra. Only 1 patient presented with severe mid shaft
      ring stricture, which required surgical revision. CONCLUSIONS: Incorporating the
      vagina of intersex patients into urethroplasty using detubularized pedicled
      vaginal onlay flap seems to provide a safe and practical method to treat severe
      hypospadias with genital ambiguity. Short-term satisfactory results are
      achievable by choosing the proper surgical approach and preserving the vaginal
      blood supply. However, longer followup in a large series of patients is needed
      before applying this method to clinical practice.

PMID- 18804821
TI  - [Passage from childhood to adulthood and craniovertebral malformations].
AB  - Craniovertebral malformations are infrequent in children. Their causes are
      numerous (Chiari, congenital bone diseases, metabolic diseases, and genetic
      anomalies). When symptomatic (seldom), these malformations require surgical
      decompression and fixation. Progress in therapy probably will postpone the
      occurrence of these signs and require cooperation between pediatric and adult
      physicians.

PMID- 18804822
TI  - [Choroid plexus carcinoma: a case report].
AB  - OBJECTIVE: Choroid plexus carcinomas are rare and occur more frequently in
      children than in adults. The differential diagnosis includes choroid plexus
      papilloma and papillary ependymoma. The prognosis is generally poor. The
      objective of this paper is to discuss the epidemiological characteristics,
      diagnosis, treatment, and prognosis of this rare childhood tumor. CASE REPORT: A
      three-year-old child was hospitalized with a history of partial epilepsy and
      intracranial hypertension. A computed tomography scan showed an intracranial mass
      measuring 11cm in diameter, extending to the ventricle system with heterogeneous
      contrast enhancement. He was urgently operated for loss of consciousness. During
      the operation, the patient developed an abundant hemorrhage and died. The
      histopathological examination of the excised tumor identified a choroid plexus
      carcinoma. CONCLUSION: Choroid plexus carcinomas are rare and treatment is
      currently controversial. Radical excision is quite difficult and associated with
      excessive blood loss.

PMID- 18804823
TI  - Diversolides A-G, guaianolides from the roots of Ferula diversivittata.
AB  - Seven sesquiterpene lactone derivatives, diversolides A-G (1-7), together with
      two known compounds, diversin (8) and stigmasterol, were isolated from the roots
      of Ferula diversivittata. The structures of these compounds were elucidated by
      extensive spectroscopic methods including 1D-(1H and 13C) and 2D-NMR experiments
      (DQF-COSY, HSQC, HMBC, and NOESY) as well as high-resolution EIMS. Compounds 1, 4
      and 6-8 were tested for their in vitro antifungal and antibacterial activities.
      Some of the tested compounds showed moderate antifungal and antibacterial
      activities with minimum inhibitory concentration (MIC) values from 40 to
      80microg/ml.

PMID- 18804824
TI  - Cycloartane glycosides from Astragalus campylosema Boiss. ssp. campylosema.
AB  - Four cycloartane glycosides, 3-O-[alpha-l-arabinopyranosyl-(1-->2)-beta-d
      xylopyranosyl]-3beta,6alpha,16beta,23alpha,25-pentahydroxy-20(R),24(S)
      epoxycycloartane (1), 3-O-[alpha-l-arabinopyranosyl-(1-->2)-beta-d-xylopyranosyl]
      16-O-hydroxyacetoxy-23-O-acetoxy-3beta,6alpha,25-trihydroxy-20(R),24(S)
      epoxycycloartane (2), 3-O-[alpha-l-arabinopyranosyl-(1-->2)-beta-d-xylopyranosyl]
      3beta,6alpha,23alpha,25-tetrahydroxy-20(R),24(R)-16beta,24;20,24
      diepoxycycloartane (3), 3-O-[alpha-l-arabinopyranosyl-(1-->2)-beta-d
      xylopyranosyl]-25-O-beta-d-glucopyranosyl-3beta,6alpha,16beta,25-tetrahydroxy
      20(R),24(S)-epoxycycloartane (4), along with three known cycloartane glycosides
      were isolated from the MeOH extract of the roots of Astragalus campylosema ssp.
      campylosema. Their structures were established by the extensive use of 1D- and 2D
      NMR experiments along with ESIMS and HRMS analysis. The occurrence of the
      hydroxyl function at position 23 (1-2) and of the ketalic function at C-24 (3)
      are very unusual findings in the cycloartane class.

PMID- 18804825
TI  - Cytotoxic and antiplasmodial substances from marine-derived fungi, Nodulisporium
      sp. and CRI247-01.
AB  - Nodulisporacid A (1) was isolated from a marine-derived fungus Nodulisporium sp.
      CRIF1, while vermelhotin (5) was obtained from an unidentified fungus CRI247-01
      (a member of the Order Pleosporales). Both 1 and 5 occurred as equilibrium E/Z
      mixtures. Ester derivatives (2 and 3) and vermelhotin (5) showed cytotoxic
      activity against eleven cancer cell lines. Nodulisporacid A (1) and vermelhotin
      (5) exhibited moderate antiplasmodial activity.

PMID- 18804826
TI  - Canine visceral leishmaniasis in urban and rural areas of Northeast Brazil.
AB  - The purpose of this study was to determine the clinical and laboratory profiles
      of canine leishmaniasis in two distinct areas. Dogs from urban and rural areas
      were examined. The population studied in the metropolitan area included 54 dogs.
      Of these, 20 (37%) animals did not present with any signs suggestive of visceral
      leishmaniasis (VL). Among these, only eight were confirmed negative by ELISA
      (rK39 and CE) and 12 dogs, clinically negative for leishmaniasis, were
      seropositive by ELISA (rK39 and CE). Thinness, conjunctivitis and onychogryphosis
      were the most frequent clinical signs in the urban areas, followed by crusty
      lesions, alopecia, ulcerated lesions, hyperkeratosis and exfoliation. In the
      metropolitan area human VL cases occurred mainly in 1991, 1992, 1999 and 2000. In
      the rural areas the ELISA rK39 test detected a seroprevalence of 11.3% and ELISA
      CE (Leishmania crude extract) of 20.6%. Thirty-nine dogs were examined 6 months
      after the first visit. Serological exams using rK39 antigen showed seroconversion
      of only one dog, whereas Leishmania CE showed seroconversion of 13 (33.4%) dogs.
      In this rural environment 83.3% of the positive dogs were asymptomatic. Lutzomyia
      intermedia and Lu. longipalpis were the most predominant sandfly vector species.
      Amastigotes were identified in spleen and liver fragments of symptomatic
      necropsied animals. PCR amplification of DNA isolated from promastigote culture
      indicated that the species was Leishmania chagasi. This finding suggests that
      delayed diagnosis and euthanasia of potentially infectious animals may occur with
      an increased transmission risk to sandflies and subsequently to humans.

PMID- 18804827
TI  - Plasmodium vivax circumsporozoite variants and Duffy blood group genotypes in the
      Brazilian Amazon region.
AB  - The circumsporozoite protein (CSP) of the Plasmodium vivax infective sporozoite
      is considered to be a major target for the development of recombinant malaria
      vaccines. The Duffy blood group molecule acts as the red blood cell receptor for
      P. vivax. We review the frequency of P. vivax CSP variants and report their
      association with the Duffy blood group genotypes from Brazilian Amazon patients
      carrying P. vivax malaria. Peripheral blood samples were collected from 155 P.
      vivax-infected individuals from five Brazilian malaria-endemic areas. The P.
      vivax CSP variants and the Duffy blood group genotypes were assessed using
      PCR/RFLP. In single infections, the VK210 variant was the commonest followed by
      the P. vivax-like variant. The typing of P. vivax indicated that the frequency of
      variants among the study areas was significantly different from one to another.
      This is the first detection of the VK247 and P. vivax-like variant in single
      infections in endemic areas of Brazil. Association of the CSP P. vivax variants
      with the heterozygous Duffy blood group system genotype was significant for VK210
      single infection. These observations provide additional data on the Plasmodium
      host interactions concerning the Duffy blood group and P. vivax capability of
      causing human malaria.

PMID- 18804829
TI  - Intestinal strongyloidiasis: a diagnosis frequently missed in the tropics.
AB  - Strongyloides stercoralis, a nematode parasite, is endemic in tropical and
      subtropical regions. Infection usually remains asymptomatic, but in
      immunocompromised hosts hyperinfection and dissemination can occur, which has a
      high mortality. Early detection of S. stercoralis may alter the fatal course of
      infection. We present our experience of five patients with S. stercoralis
      hyperinfection diagnosed by endoscopic duodenal and jejunal biopsy in northern
      India. A predisposing factor was present in all patients in the form of
      corticosteroid intake, chronic liver disease and panhypogammaglobulinaemia.
      Common gastrointestinal symptoms were abdominal pain, diarrhoea, gastrointestinal
      bleeding, nausea, vomiting and weight loss with evidence of malabsorption. The
      initial stool examination and peripheral blood eosinophil count were normal in
      all patients. Strongyloidiasis was not suspected clinically in any patient and
      the diagnosis was achieved on endoscopic biopsy. Three of the patients with
      disseminated disease developed fatal Gram-negative systemic infection. This study
      highlights the importance of considering strongyloidiasis in all patients on
      immunosuppressive drug therapy who present with gastrointestinal symptoms so that
      the patient can be appropriately investigated and promptly treated. In endemic
      regions, patients with systemic Gram-negative bacterial infections without an
      obvious cause should be tested for strongyloidiasis.

PMID- 18804830
TI  - Neurocysticercosis in patients with active epilepsy from the pig farming
      community of Lucknow district, north India.
AB  - Epilepsy is a major health problem worldwide, and neurocysticercosis (NCC) is one
      of the important causes of epilepsy in the tropics. The present study was carried
      out in a rural pig farming community of north India to estimate the prevalence of
      NCC in patients with active epilepsy (AE) and to determine the associated risk
      factors. Based on 30-cluster sampling recommended by WHO, a total of 1640
      individuals belonging to 294 families from 30 villages were enrolled in the
      study. Demographic and socio-economic details of all individuals and families
      were recorded. Individuals with AE were identified by door-to-door survey. NCC
      was diagnosed by clinical, immunological, neuroimaging (brain magnetic resonance
      imaging) and epidemiological criteria. During the survey, 95 (5.8%) patients with
      AE were identified and clinically confirmed; 91 agreed to further evaluation for
      NCC and 44 (48.3%) of them fulfilled either definitive or probable diagnostic
      criteria for NCC. These 44 patients belonged to 37 households. Epilepsy in the
      family and no separate place for keeping pigs were identified as risk factors for
      NCC clustering in a family. The study shows a very high prevalence of AE in the
      pig farming community and NCC as its major cause. Since NCC is a preventable and
      potentially eradicable disease, appropriate intervention strategies may help to
      reduce the disease burden.

PMID- 18804831
TI  - Resonant ultrasound spectroscopy and homogeneity in polycrystals.
AB  - Resonant ultrasound spectroscopy (RUS) is capable of determining the bulk elastic
      properties of a solid from its characteristic vibration frequencies, given the
      dimensions, density and shape of the sample. The model used for extracting values
      of the elastic constants assumes perfect homogeneity, which can be approximated
      by average-isotropic polycrystals. This approximation is excellent in the small
      grain regime assumed for most averaging procedures, but for real samples with
      indeterminate grain size distributions, it is not clear where the approximation
      breaks down. RUS measurements were made on pure copper samples where the grain
      size distribution was changed by progressive heat treatments in order to find a
      quantitative limit for the loss of homogeneity. It is found that when a measure
      of the largest grains is 15% of the sample's smallest dimension, the deviation in
      RUS fits indicates elastic inhomogeneity.

PMID- 18804832
TI  - Guided ultrasonic waves for non-destructive monitoring of the stress levels in
      prestressed steel strands.
AB  - The safety of prestressed civil structures such as bridges, dams, nuclear power
      plants, etc. directly involves the security of both environment and users. Health
      monitoring of the tensioning components, such as strands, tendons, bars,
      anchorage bolts, etc. is an important research topic and a challenging task
      bringing together the non-destructive evaluation (NDE) and civil engineering
      communities. This paper deals with a guided ultrasonic wave procedure for
      monitoring the stress levels in seven-wire steel strands (15.7 mm in diameter).
      The mechanical and geometrical characteristics of the prestressed strands were
      taken into account for optimizing the measurement configuration and then the
      choice of the guided ultrasonic mode at a suitable frequency. Simplified
      acoustoelastic formulations were derived from the acoustoelasticity theory
      according to either calibration test or in situ measurement. The results from
      acoustoelastic measurements on the seven-wire steel strands are presented and
      discussed in the case of calibration tests and industrially prestressed strands.
      They show the potential and the suitability of the proposed guided wave method
      for evaluating the stress levels in the tested seven-wire steel strands.

PMID- 18804833
TI  - Development of a new cucumber mosaic virus-based plant expression vector with
      truncated 3a movement protein.
AB  - We have developed a Cucumber mosaic virus (CMV)-based expression vector for the
      production of heterologous proteins in plants. Cell-to-cell movement of CMV is
      dependent on the presence of coat protein (CP). Previous studies have shown that
      deletion of 33 amino acids (aa) from the carboxy-terminus of the 3a movement
      protein facilitates cell-to-cell movement that is independent of CP. The CMV
      based expression vector that we have designed utilizes this truncated 3a protein,
      allowing the expression of target genes from the strong CP subgenomic promoter
      and without the need for providing CP in trans for cell-to-cell spread. Using
      this vector we achieved expression levels of ~450 mg/kg leaf tissue of green
      fluorescent protein (GFP) when the vector was delivered into Nicotiana
      benthamiana plants by agroinfiltration. Human growth hormone (hGH), on the other
      hand, accumulated to ~170 mg/kg of leaf tissue when the same approach was used to
      deliver the vector.

PMID- 18804834
TI  - Molecular studies of temperature-sensitive replication of the cold-adapted B/Ann
      Arbor/1/66, the master donor virus for live attenuated influenza FluMist
      vaccines.
AB  - Cold-adapted (ca) B/Ann Arbor/1/66 is the master donor virus for influenza B (MDV
      B) vaccine component of live attenuated influenza FluMist vaccine. The six
      internal protein gene segments of MDV-B confer the characteristic cold-adapted
      (ca), temperature-sensitive (ts) and attenuated (att) phenotypes to the
      reassortant vaccine strains that contain the HA and NA RNA segments from the
      circulating wild type strains. Previously, we have mapped the loci in the NP, PA
      and M genes that determine the ca, ts and att phenotypes of MDV-B. In this
      report, the ts mechanism of MDV-B was described by comparing replication of MDV-B
      with its wild type counterpart at permissive and restricted temperatures. We
      showed that the PA and NP proteins of MDV-B are defective in RNA polymerase
      function at the restricted temperature of 37 degrees C resulting in greatly
      reduced viral RNA and protein synthesis. In addition, the two M1 residues, Q159
      and V183 that are unique to MDV-B, contribute to reduced virus replication at
      temperatures greater than 33 degrees C, possibly due to the reduced M1 membrane
      association and its reduced virion M1 incorporation. Thus, the previously
      identified MDV-B loci not only reduce viral polymerase function at the restricted
      temperature but also affect virus assembly and release.

PMID- 18804835
TI  - Comparing the partitioning behavior of Giardia and Cryptosporidium with that of
      indicator organisms in stormwater runoff.
AB  - Microbial association with particles can significantly affect the fate and
      transport characteristics of microbes in aquatic systems as particle-associated
      organisms will be less mobile in the environment than their free phase (i.e.
      unattached) counterparts. As such, similarities or dissimilarities in the
      partitioning behavior of indicator organisms and pathogens may have an impact on
      the suitability of a particular indicator to act as a surrogate for a pathogen.
      This research analyzed the partitioning behavior of two pathogens
      (Cryptosporidium, Giardia) and several common indicator organisms (fecal
      coliform, Escherichia coli, Enterococci, Clostridium perfringens spores, and
      coliphage) in natural waters under both dry and wet weather conditions. Samples
      were taken from several streams in two distinct sampling phases: (i) single grab
      samples; and (ii) intrastorm samples obtained throughout the duration of four
      storms. Partitioning behavior varied by microbial type, with 15-30% of bacterial
      indicators (fecal coliform, E. coli, and Enterococci) associated with settleable
      particles compared to 50% for C. perfringens spores. Both pathogens exhibited
      similar levels of particle association during dry weather (roughly 30%), with
      increased levels observed during wet weather events (Giardia to 60% and
      Cryptosporidium to 40%). The settling velocities of particle-associated microbes
      were also estimated, with those of the bacterial indicators (fecal coliform, E.
      coli, and Enterococci), as well as C. perfringens spores, being similar to that
      of the Giardia and Cryptosporidium, suggesting these organisms may exhibit
      similar transport behavior. With respect to intrastorm analysis, the highest
      microbial concentrations, in both particle-associated and free phase, occurred
      during the earlier stages of a storm. The total loadings of both indicators and
      pathogens were also estimated over the course of individual storms.

PMID- 18804836
TI  - Antimicrobial nanomaterials for water disinfection and microbial control:
      potential applications and implications.
AB  - The challenge to achieve appropriate disinfection without forming harmful
      disinfection byproducts by conventional chemical disinfectants, as well as the
      growing demand for decentralized or point-of-use water treatment and recycling
      systems calls for new technologies for efficient disinfection and microbial
      control. Several natural and engineered nanomaterials have demonstrated strong
      antimicrobial properties through diverse mechanisms including photocatalytic
      production of reactive oxygen species that damage cell components and viruses
      (e.g. TiO2, ZnO and fullerol), compromising the bacterial cell envelope (e.g.
      peptides, chitosan, carboxyfullerene, carbon nanotubes, ZnO and silver
      nanoparticles (nAg)), interruption of energy transduction (e.g. nAg and aqueous
      fullerene nanoparticles (nC(60))), and inhibition of enzyme activity and DNA
      synthesis (e.g. chitosan). Although some nanomaterials have been used as
      antimicrobial agents in consumer products including home purification systems as
      antimicrobial agents, their potential for disinfection or microbial control in
      system level water treatment has not been carefully evaluated. This paper reviews
      the antimicrobial mechanisms of several nanoparticles, discusses their merits,
      limitations and applicability for water disinfection and biofouling control, and
      highlights research needs to utilize novel nanomaterials for water treatment
      applications.

PMID- 18804837
TI  - Seasonal variation of extracellular enzymatic activity (EEA) and its influence on
      metal speciation in a polluted salt marsh.
AB  - The influence of salt marsh sediment extracellular enzymatic activity (EEA) on
      metal fractions and organic matter cycling was evaluated on a seasonal basis, in
      order to study the relation between organic matter cycles and the associated
      metal species. Metals in the rhizosediment of Halimione portulacoides were
      fractioned according to the Tessier's scheme and showed a similar pattern
      regarding the organic-bound fraction, being always high in Autumn, matching the
      season when organic matter presented higher values. Both organic-bound and
      residual fractions were always dominant, being the seasonal variations due to
      interchanges between these two fractions. Phenol oxidase and beta-N
      acetylglucosaminidase had higher activities during the Spring and Summer,
      contrarily to peroxidase which had higher activity during Winter. Protease showed
      high activities in both Spring and Winter. These different periods of high
      organic matter hydrolysis caused two periods of organic metal bound decrease.
      Sulphatase peaks (Spring and Winter) matched the depletion of exchangeable metal
      forms, probably due to sulphides formation and consequent mobilization. This
      showed an interaction between several microbial activities affecting metal
      speciation.

PMID- 18804838
TI  - Soil vapor extraction in sandy soils: influence of airflow rate.
AB  - Airflow rate is one of the most important parameters for the soil vapor
      extraction of contaminated sites, due to its direct influence on the mass
      transfer occurring during the remediation process. This work reports the study of
      airflow rate influence on soil vapor extractions, performed in sandy soils
      contaminated with benzene, toluene, ethylbenzene, xylene, trichloroethylene and
      perchloroethylene. The objectives were: (i) to analyze the influence of airflow
      rate on the process; (ii) to develop a methodology to predict the remediation
      time and the remediation efficiency; and (iii) to select the most efficient
      airflow rate. For dry sandy soils with negligible contents of clay and natural
      organic matter, containing the contaminants previously cited, it was concluded
      that: (i) if equilibrium between the pollutants and the different phases present
      in the soil matrix was reached and if slow diffusion effects did not occur,
      higher airflow rates exhibited the fastest remediations, (ii) it was possible to
      predict the remediation time and the efficiency of remediation with errors below
      14%; and (iii) the most efficient remediation were reached with airflow rates
      below 1.2 cm(3)s(-1) standard temperature and pressure conditions.

PMID- 18804839
TI  - Spectroscopic changes on fulvic acids from a kraft pulp mill effluent caused by
      sun irradiation.
AB  - Large volumes of wastewater with a high organic load are generated by the pulp
      and paper industry that negatively affect the quality of receiving waters. The
      main waste products in the pulp mill effluents are lignin derived macromolecular
      compounds, which are similar to natural humic substances and very resistant to
      wastewater treatments. Fulvic acids (FA) represent the higher percentage of these
      humic substances and it was observed that solar irradiation modify their
      properties. Several analytic tools, namely, UV-Visible, molecular fluorescence
      and FTIR spectroscopies, were used to assess the effect of solar exposition on
      fulvic acids from a kraft pulp mill effluent. It may be concluded that sun
      irradiation may alter to a high extent the physicochemical properties of
      macromolecular organic matter, namely fulvic acids, released by kraft pulp mill
      effluents. After solar exposition, the aromaticity decreases, the aliphatic
      structures become more oxygenated, and the fulvic acids from the pulp mill
      effluent remaining in solution are more similar to aquatic fulvic acids from non
      polluted sites.

PMID- 18804840
TI  - Contamination by polybrominated diphenyl ethers of sediments from the Lake
      Maggiore basin (Italy and Switzerland).
AB  - Polybrominated diphenyl ethers (PBDEs) are characterized by chemical properties
      and toxicological profiles similar to other POPs (persistent organic pollutants)
      included in the EU Priority Pollutant List (2455/01/CE). However, limited data
      have been available for these compounds thus far for Italian freshwater abiotic
      matrices. Lake Maggiore basin, a heavily industrialized and densely populated
      area, was selected for studying PBDE contamination in Italy. PBDEs and OCs
      (organochlorine compounds) in the basin were quantified by analysing both
      sediment cores collected in 2005 from the lake and grab samples from the main
      tributaries and the emissary. Fourteen PBDEs, from tri-BDE to hepta-BDE congeners
      and BDE209, were compared with some organochlorine POPs (PCBs and DDTs)
      characterizing Lake Maggiore basin contamination. Analyses of tri-to hepta-BDEs,
      PCBs and DDTs were undertaken by GC-MS/MS, while BDE-209 was analysed by GC/ECD.
      Results showed a dominant presence of BDE-209 (>95% of SigmaBDE) and limited
      amounts of BDE-47, BDE-99, BDE-100, BDE-153 and BDE-154. Lake core profiles
      highlighted a decreasing trend in PCB concentrations starting from the year 2000,
      while PBDEs showed greater concentrations after the beginning of the 1990s (up to
      30 ng g(-1)d.w.). Among the tributaries, the Bardello and Boesio rivers were the
      most PBDE-contaminated (up to 290 ng g(-1)d.w.).

PMID- 18804841
TI  - The mechanism and kinetics of ultrasound-enhanced electrochemical oxidation of
      phenol on boron-doped diamond and Pt electrodes.
AB  - The research on ultrasound (US) enhanced electrochemical oxidation of Phenol (Ph)
      on boron-doped diamond (BDD) and Pt electrodes is studied. The enhancement by US
      on BDD is much greater than for Pt. With the assistance of US, the degradation
      rate and current efficiency on BDD are increased by 301% and 100%, respectively,
      while those on Pt are 51% and 49%. The difference of the enhancement on these two
      electrodes is caused by the fact that mass transport, adsorption amount and
      electrode reaction affected by US on BDD are different from those of Pt. The
      kinetics investigation on intermediates formed during electrochemical degradation
      show that the variety of intermediates produced on BDD is less than for Pt. In
      the presence of US, on both electrodes, no change occurred to the amounts of the
      intermediate species. However, time for intermediates to reach the highest
      concentration is cut down. This effect for degradation of Ph on BDD is more
      obvious than for Pt. The present research indicates that BDD is suitable for
      degradation of Ph by US assisted electrochemical oxidation.

PMID- 18804842
TI  - Decomposing phenol by the hidden talent of ferromagnetic nanoparticles.
AB  - Researches on modified Fenton reactions applied in phenol degradation have been
      focused on reducing secondary pollution and enhancing catalytic efficiency. Newly
      developed methods utilizing carriers, such as Resin and Nafion, to immobilize
      Fe(2+) could avoid iron ion leakage. However, the requirement of high temperature
      and the limited reaction efficiency still restrained them from broad application.
      Based on a recently discovered "hidden talent" of ferromagnetic nanoparticles
      (MNPs), we established a MNP-catalyzed phenol removal assay, which could overcome
      these limitations. Our results showed that the MNPs removed over 85% phenol from
      aqueous solution within 3h even at 16  degrees C. The catalytic condition was
      extensively optimized among a range of pH, temperature as well as initial
      concentration of phenol and H(2)O(2). TOC and GC/MS analysis revealed that about
      30% phenol was mineralized while the rest became small molecular organic acids.
      Moreover the MNPs were thermo-stable and could be regenerated for at least five
      rounds. Thus, our findings open up a wide spectrum of environmental friendly
      applications of MNPs showing several attractive features, such as easy
      preparation, low cost, thermo-stability and reusability.

PMID- 18804843
TI  - Effects of intensive urbanization on the intrusion of shallow groundwater into
      deep groundwater: examples from Bangkok and Jakarta.
AB  - Asian megacities have severe pollution problems in both coastal and urban areas.
      In addition, the groundwater potential has decreased and land subsidence has
      occurred because of intensive groundwater pumping in urban areas. To prevent the
      adverse effects of urbanization on groundwater quality, it is necessary to
      confirm the changes in groundwater flow and contaminant transport caused by
      urbanization. We examined the effects of urbanization on contaminant transport in
      groundwater. The research areas were located around Bangkok, Thailand, and
      Jakarta, Indonesia, cities with populations of approximately 8 and 12 million,
      respectively. Each metropolitan city is located on a river delta and is adjacent
      to a bay. We measured the water level and collected water samples at boreholes at
      multiple depths (100 to 200 m) in 2004 and 2006 in Bangkok and Jakarta,
      respectively. The current hydraulic potential is below sea level in both cities
      because of prior excess abstraction of groundwater. As a result, the direction of
      groundwater flow is now downward in the coastal area. The Cl(-) concentration and
      delta(18)O distributions in groundwater suggest that the decline in hydraulic
      potential has caused the intrusion of seawater and shallow groundwater into deep
      groundwater. Concentrations of Mn and NO3(-)-N in groundwater suggest the
      intrusion of these contaminants from shallow to deep aquifers with downward
      groundwater flow and implies an accumulation of contaminants in deep aquifers.
      Therefore, it is important to recognize the possibility of future contaminant
      transport with the discharge of deep groundwater into the sea after the recovery
      of groundwater potential in the coastal areas.

PMID- 18804844
TI  - Direct radiative forcing due to aerosols in Asia during March 2002.
AB  - The Asian dust aerosol model (ADAM) and the aerosol dynamic model including the
      gas-aerosol interaction processes together with the Column Radiation Model (CRM)
      of Community Climate Model 3 and the output of the fifth generation of meso-scale
      model (MM5) in a grid 60 x 60 km2 in the Asian domain (70-150E, Equator-50N) have
      been employed to estimate direct radiative forcing of the Asian dust and the
      anthropogenic aerosols including the BC, OC, secondary inorganic aerosol (SIA),
      mixed type aerosol (dust+BC+OC+SIA) and sea salt aerosols at the surface, the top
      of atmosphere (TOA) and in the atmosphere for the period of 1-31 March 2002
      during which a severe Asian dust event has been occurred in the model domain. The
      results indicate that the ADAM model and the aerosol dynamic model simulate quite
      well the spatial and temporal distributions of the mass concentration of aerosols
      with the R2 value of more than 0.7. The estimated mean total column aerosol mass
      in the analysis domain for the whole period is found to be about 78 mg m(-2), of
      which 66% and 34% are, respectively, contributed by the Asian dust aerosol and
      all the other anthropogenic aerosols. However, the direct radiative forcing
      contributed by the Asian dust aerosol is about 22% of the mean radiative forcing
      at the surface (-6.8 W m(-2)), about 31% at the top of atmosphere (-2.9 W m(-2))
      and about 13% in the atmosphere (3.8 W m(-2)), suggesting relatively inefficient
      contribution of the Asian dust aerosol on the direct radiative forcing compared
      to the anthropogenic aerosols. The aerosol direct radiative forcing at the
      surface is mainly contributed by the mixed type aerosol (30%) and the SIA aerosol
      (25%) while at the top of atmosphere it is mainly contributed by the SIA aerosol
      (43%) and the Asian dust aerosol (31%) with positively (warming) contributed by
      BC and mixed type aerosols. The atmosphere is warmed mainly by the mixed type
      aerosol (55%) and the BC aerosol (26%). However, the largest radiative intensity
      of direct radiative forcing of aerosols is the BC aerosol.

PMID- 18804845
TI  - Delivery and cycling of phosphorus in rivers: a review.
AB  - Phosphorus (P) supply (concentration and flux) is an important driver for
      biological activity in flowing waters and needs to be managed to avoid
      eutrophication impacts associated with urbanisation and agricultural
      intensification. This paper examines the role of in-stream retention and cycling
      in regulating river P concentrations in order to better understand the links
      between P sources and their ecological impacts. In terms of their composition
      (solubility and concentration), patterns of delivery (mode and timing) and
      therefore ecological relevance, P sources entering rivers are best grouped into
      wastewater discharges > runoff from impervious surfaces (roads, farmyards) >
      runoff from pervious surfaces (forestry, cultivated land and pasture). The
      localized impacts of soluble P discharges during ecologically sensitive periods
      can be distinguished from the downstream impacts associated with particulate P
      discharges under high flows due to the different processes by which these sources
      are retained, transformed and assimilated within the river channel. The range of
      physico-chemical processes involved in P cycling and the variable importance of
      these processes in different river environments according to stream size, stream
      geomorphology and anthropogenic pressures are summarised. It is concluded that
      the capacity to retain (process) P within the river channel, and hence regulate
      the downstream delivery of P without stressing the aquatic communities present,
      is considerable, especially in headwaters. To help achieve good water quality,
      there is scope to better manage this ecosystem service through regulation of P
      supply whilst optimising in-stream P retention according to subsidy-stress
      theory. Further research is needed to develop in-stream management options for
      maximising P subsidies and to demonstrate that regulation of downstream P
      delivery will reduce the incidence of eutrophication in connected waterbodies.

PMID- 18804846
TI  - Extremely low frequency-magnetic fields (ELF-EMF) occupational exposure and
      natural killer activity in peripheral blood lymphocytes.
AB  - Extremely Low Frequency-Magnetic Fields (ELF-MF) are possible carcinogens to
      humans and some data suggest that they can act as promoters or progressors. Since
      NK cells play a major role in the control of cancer development, an adverse
      effect on ELF-MF on NK function has been hypothesized. We examined NK activity in
      52 workers exposed to different levels of ELF-MF in various activities.
      Individual exposure was monitored during 3 complete work-shifts using personal
      dosimeters. Environmental exposure was also monitored. ELF-MF levels in the
      workers were expressed as Time-Weighted Average (TWA) values. NK activity was
      measured in peripheral blood lymphocytes (PBL). In the whole group the median
      occupational TWA was 0.21 microT. According to the TWA levels, workers were
      classified as low exposed (26 subjects, TWA < or =0.2 microT) and higher exposed
      workers (26 subjects; TWA >0.2 microT). In higher exposed workers, we observed a
      trend to reduce NK activity compared to low exposed, but the difference was not
      significant. Then we selected a subgroup of highest exposed workers (12 subjects;
      TWA >1 microT); no difference was observed between low and highest exposed
      subjects in the main personal variables. Considering both E:T ratios from 12:1 to
      50:1 and Lytic Units, a significant reduction in NK activity was observed in the
      highest exposed workers compared to the low exposed. Multivariate analysis showed
      a significant negative correlation between exposure and LU, while no correlation
      was evidenced with other personal characteristics. ELF-MF are considered possible
      carcinogens, and existing data suggest that they can act as promoters. Due to the
      role of NK activity in host defence against cancer, the results obtained in this
      study in workers exposed to ELF-MF levels exceeding 1 microT are in agreement
      with this hypothesis, and support the need for further investigation in this
      field.

PMID- 18804847
TI  - Antibacterial agents and heavy metal resistance in Gram-negative bacteria
      isolated from seawater, shrimp and sediment in Iskenderun Bay, Turkey.
AB  - The aim of the present study was to determine the level of antibiotic resistance
      patterns and distribution of heavy metal resistance of bacterial isolates from
      seawater, sediment and shrimps, and to determine if there is a relationship
      between antibiotic and heavy metal resistance. We undertook studies in 2007 in
      the industrially polluted Iskenderun Bay, on the south coast of Turkey. The
      resistance of 236 Gram-negative bacterial isolates (49 from seawater, 90 from
      sediment and 97 from shrimp) to 16 different antibiotics, and to 5 heavy metals,
      was investigated by agar diffusion and agar dilution methods, respectively. A
      total of 31 species of bacteria were isolated: the most common strains isolated
      from all samples were Escherichia coli (11.4%), Aeromonas hydrophila (9.7%) and
      Stenotrophomonas maltophilia (9.3%). There was a high incidence of resistance to
      ampicillin (93.2%), streptomycin (90.2%) and cefazolin (81.3%), and a low
      incidence of resistance to imipenem (16.5%), meropenem (13.9%) and cefepime
      (8.0%). Some 56.8% of all bacteria isolated from seawater, sediment and shrimp
      were resistant to 7 or more antibiotics. Most isolates showed tolerance to
      different concentrations of heavy metals, and minimal inhibition concentrations
      ranged from 12.5 microg/ml to > 3200 microg/ml. The bacteria from seawater,
      sediment and shrimp showed high resistance to cadmium of 69.4%, 88.9%, and 81.1%
      respectively, and low resistance to manganese of 2%, 6.7% and 11.3% respectively.
      The seawater and sediment isolates which were metal resistant also showed a high
      resistance to three antibiotics: streptomycin, ampicillin and trimethoprim
      sulphamethoxazole. In contrast, the shrimp isolates which were metal resistant
      were resistant to four antibiotics: cefazolin, nitrofurantoin, cefuroxime and
      ampicillin. Our results show that Iskenderun Bay has a significant proportion of
      antibiotic and heavy metal resistant Gram-negative bacteria, and these bacteria
      constitute a potential risk for public health.

PMID- 18804848
TI  - The impact of the PAI-1 4G/5G polymorphism on the outcome of patients with
      ALI/ARDS.
AB  - INTRODUCTION: Increased levels of plasminogen activator inhibitor-1 (PAI-1) have
      been associated with worse outcome in ALI/ARDS. A single guanosine
      insertion/deletion (4G/5G) polymorphism in the promoter region of the PAI-1 gene,
      may play an important role in the regulation of PAI-1 expression. The objective
      of the study was to evaluate the effect of this polymorphism on the outcome of
      critically ill patients with ALI/ARDS. MATERIALS AND METHODS: 52 consecutive
      ventilated patients with ALI/ARDS were studied. Bronchoalveolar lavage was
      performed within 48 hours from diagnosis. Measurement of plasma and BALF PAI-1
      activity and D-dimers levels, and 4G/5G genotyping of PAI-1 were carried out. The
      primary outcome was 28-day mortality, and secondary outcomes included organ
      dysfunction and ventilator-free days. RESULTS: 17 patients were homozygotes for
      the 4G allele. Severity scores were not different between subgroups upon study
      enrollment. 28-day mortality was 70.6% and 42.9% for the 4G-4G and the non-4G-4G
      patients, respectively (p=0.06). PAI-1 activity levels and D-dimer in plasma and
      BALF were not significantly different between the 4G-4G and the non-4G-4G
      subgroups. In the multivariate analysis, genotype 4G/4G was the only variable
      independently associated with 28-day mortality (Odds Ratio=9.95, 95% CI: 1.79
      55.28, p=0.009). Furthermore, genotype 4G/4G and plasma PAI-1 activity levels
      were independently negatively associated with ventilator free days (p=0.033 and
      p=0.008, respectively). CONCLUSIONS: ALI/ARDS patients, homozygous for the 4G
      allele of the PAI-1 gene, experienced higher 28-day mortality. This genotype was
      associated with a reduction in the number of days of unassisted ventilation and
      was inversely associated with the number of days without organ failure.

PMID- 18804849
TI  - Laparoscopy training in gynecologic oncology fellowship programs.
AB  - OBJECTIVE: To assess the adequacy of laparoscopic surgical training as perceived
      by gynecologic oncology fellows-in-training and to compare current opinions to
      those on a 2003 survey. STUDY DESIGN: Fellows were surveyed via mail or an
      internet website. RESULTS: Seventy-eight (64%) of 121 fellows responded. One
      hundred percent now state that laparoscopy is important or very important in
      gynecologic oncology practice compared to 86% in 2003. Ninety-five percent
      reported that much or maximum emphasis should be placed on laparoscopic training
      compared to 70% previously. Currently, 69% believe that their fellowship training
      in laparoscopy is very good or good compared to only 25% who felt this way 4
      years ago. Importantly, fellows now believe they are getting better laparoscopic
      training in fellowship than they did in residency. Seventy-eight percent stated
      that their perceived laparoscopic skills were good or very good. Upon completion
      of fellowship, 94% plan to perform >/=6 cases per month laparoscopically.
      CONCLUSIONS: Respondents believe that laparoscopic training should be emphasized
      in fellowship training and perceive their laparoscopic training to be
      significantly improved compared to 2003. They also envision a key role for
      laparoscopy in their future practice.

PMID- 18804850
TI  - Validation of the accuracy of the sentinel lymph node procedure in patients with
      vulvar cancer: results of a multicenter study in Germany.
AB  - OBJECTIVE: To investigate the diagnostic accuracy of the sentinel node procedure
      in patients with vulvar cancer, a multicenter study was launched in Germany in
      2003 involving 7 oncology centers. PATIENTS AND METHODS: Between 2003 and 2006,
      127 women with primary T1-T3 vulvar cancer were entered in the study and treated
      with sentinel node removal after application of (99m)Technetium labeled
      nanocolloid and/or blue dye. Subsequently, in all women a complete inguinofemoral
      lymphadenectomy and the adequate vulvar operation were performed. Sentinel lymph
      nodes were examined by routine pathologic examination (H&E), followed by step
      sectioning and immunhistochemistry if negative. RESULTS: The sentinel node
      procedure was successful in 125 out of 127 cases, in 2 cases no sentinel nodes
      were detected. 21 patients received unilateral lymphadenectomy, 103 women were
      operated on both groins. In 39 women out of 127, positive lymph nodes in one or
      both groins were identified (30.7%). In 36 women, the sentinel nodes were also
      positive (sensitivity 92.3%). We had three cases with a false negative sentinel
      node (false negative rate: 7.7%), all of these women presenting with tumors in
      midline position. One tumor was a T1 tumor (10 mm), 2 tumors being classified as
      T2 (40 and 56 mm, respectively). In one additional case (18 mm T1 tumor, midline
      position), the sentinel was positive in the right groin, but false negative on
      the left side. CONCLUSIONS: This study shows that identification of SLN in
      squamous cell cancer of the vulva is feasible, however not highly accurate
      depending on tumor localization and size. The false negative rate seems to be
      acceptable if the procedure is restricted to stage 1 tumors with clinically
      negative lymph node status. Tumors situated in or close to the midline seem to be
      less suitable for this procedure. Implementation of SLNB into clinical practice
      should be performed with care and only by experienced teams as to avoid
      preventable groin relapses.

PMID- 18804851
TI  - Innate responsiveness of CD8 memory T-cell populations nonspecifically inhibits
      allergic sensitization.
AB  - BACKGROUND: Infection or stimulation of the innate immune system by nonspecific
      microbial antigens is thought to educate the immune system to respond
      appropriately to allergens, preventing allergy. OBJECTIVE: To determine the
      immunologic pathways that might explain how infection/microbial exposure inhibits
      allergic sensitization. METHODS: Immunologic studies of non-antigen-specific
      functions of CD8 memory cells, their maturation in vivo, and their effects in a
      mouse asthma model, to test the hypothesis that CD8 memory is shaped by innate
      immunity in a way that can inhibit allergic disease. RESULTS: We found that CD8
      memory T-cell (CD8 Tm) populations bridge innate and adaptive immunity by
      responding to either antigen or cytokines alone. CD8 Tm populations partially
      subvert the clonal selection process by activating their neighbors through
      induction of dendritic cell IL-12. Stimulation of innate or acquired immunity in
      the lung or gut causes expansion/maturation of CD8 Tm populations, which provide
      an early source of cytokines, enhance T(H)1 immunity, and inhibit allergic
      sensitization and airway inflammation/hyperresponsiveness in a non-antigen
      specific fashion. CONCLUSION: CD8 T-cell-mediated immune memory is long-lived and
      can retain its capacity for rapid cytokine release in a nonantigen-specific
      fashion. This novel type of memory enhances T(H)1 over T(H)2 immunity and
      prevents allergic sensitization after exposure to environmental antigens or
      infection.

PMID- 18804852
TI  - Immunosuppression of TH2 responses in Trichinella spiralis infection by
      Helicobacter pylori neutrophil-activating protein.
AB  - BACKGROUND: The Helicobacter pylori neutrophil-activating protein (HP-NAP) is
      able to induce IL-12 expression by cells of innate immunity and to shift to T(H)1
      human allergen-specific T(H)2 cells in vitro. OBJECTIVE: We performed an in vivo
      investigation of the ability of HP-NAP to downmodulate the T(H)2 response induced
      in mice by Trichinella spiralis infection. METHODS: Groups of T spiralis-infected
      BALB/c mice received intraperitoneal PBS/rat IgG2b (control animals) or 10 microg
      of HP-NAP with or without anti-Toll-like receptor 2 antibody on days 10 and 28
      after infection. Blood eosinophils, total and T spiralis-specific IgE levels, and
      cytokine levels were measured in the plasma up to day 42, when splenocytes were
      cultured for cytokine production. RESULTS: Although control animals showed
      significant eosinophilia and increase of total and T spiralis-specific IgE, IL-4,
      and IL-5 levels from days 10 to 14, HP-NAP-treated animals showed less
      eosinophilia and total and excretory/secretory antigens of T spiralis-specific
      IgE in the blood. HP-NAP-treated animals also had higher IL-12 and IFN-gamma
      plasma levels and lower IL-4 and IL-5 levels. The addition of anti-Toll-like
      receptor 2 antibody abrogated the anti-T(H)2/pro-T(H)1 activity of HP-NAP.
      CONCLUSION: This study provides evidence that HP-NAP enhances endogenous IL-12
      and IFN-gamma response and exerts a powerful anti-T(H)2 activity in vivo,
      targeting both IL-5-induced eosinophilia and IL-4-mediated hyper-IgE responses
      induced by parasitic infection.

PMID- 18804853
TI  - Efficiency of human lactoferrin transgenic donor cell preparation for SCNT.
AB  - The combination of somatic cell nuclear transfer (SCNT) and transgenic technology
      leads to the production of transgenic cloned animals, wherein the preparation of
      competent transgenic donor cells is the pivotal upstream step. The purpose of
      this study was to establish an efficient procedure to prepare human lactoferrin
      (hLTF) transgenic donor cells for SCNT. Thus, two cell culture systems were
      employed: caprine mammary epithelial cells (for evaluation of the hTLF transgenic
      expression in vitro), and fetal-derived fibroblast cells (for identification of
      competent transgenic donor cells). Induced by hormonal signals, recombinant hLTF
      was detected in the supernatant of transfected mammary epithelial cells by
      Western blot. Reliable hLTF transgenic fibroblast cell clones were identified by
      screening with multiple PCR amplification, EGFP fluorescence, and chromosomal
      counting (32.5+/-2.3%). This study may provide an effective upstream system to
      prepare SCNT donor cells for the production of human recombinant pharmaceuticals
      from the milk of transgenic animals.

PMID- 18804854
TI  - Age-related body weight constraints on prenatal and milk provisioning in Iberian
      red deer (Cervus elaphus hispanicus) affect allocation of maternal resources.
AB  - Maternal phenotypic characteristics can influence key life history variables of
      their offspring through maternal effects. In this study, we examined how body
      size constraints on maternal weight in yearling and subadult compared to adult
      hinds (age class effects) affected prenatal (calf birth weight, calf to hind
      weight ratio) and postnatal (milk) provisioning of Iberian red deer calves. Age
      correlated with all prenatal and postnatal investment traits except calf gains,
      although correlations were weaker than those with maternal weight. Once the
      effect of linear increase in weight with age was removed from models, yearlings
      showed additional reductions in calf birth weight, calf gains, and milk
      provisioning. The low-calf birth weight might increase the risk of calf mortality
      during lactation, as this occurs primarily during the first day of life and is
      strongly related to birth weight. Yearlings showed a greater prenatal allocation
      of resources in terms of greater calf to hind weight ratio probably as an extra
      effort by yearling mothers to balance calf neonatal mortality. It might
      compensate young mothers to produce low-quality calves while still growing rather
      than waiting for the uncertain possibility of surviving to the next reproductive
      season.

PMID- 18804855
TI  - Mechanical properties of experimental dental composites containing a combination
      of mesoporous and nonporous spherical silica as fillers.
AB  - OBJECTIVES: Mesoporous fillers have been investigated for use in dental
      composites because of their potential for creating micromechanical filler/resin
      matrix interphase bonding. Such a micromechanical bonding could eliminate the
      need for the silane treatment of fillers for interfacial chemical bonding that is
      prone to hydrolysis in the oral environment. In the case of micromechanical
      bonding, dental polymer chains are threaded mechanically (like a "necklace")
      through nanosized channels in the fillers. METHODS: A combination of mesoporous
      silica, which was synthesized using the non-surfactant templating method, and
      nonporous spherical silica (500nm) was used to prepare experimental dental
      composites. The porous silica used in this study contained interconnected pores
      and channels as opposed to porous fillers containing surface pores. The
      compressive strength, compressive modulus, flexural modulus, and flexural
      strength of these composites were evaluated. RESULTS: The results showed that
      composites containing a combination of mesoporous and nonporous fillers have
      better mechanical properties than the composites having either of these fillers
      alone. SIGNIFICANCE: The results showed that a combination of mesoporous and
      nonporous materials can be used to prepare stronger dental materials that may
      resist hydrolysis and wear.

PMID- 18804856
TI  - Impact of thermal properties of veneering ceramics on the fracture load of
      layered Ce-TZP/A nanocomposite frameworks.
AB  - OBJECTIVES: The aim of this in vitro study was to assess the influence of thermal
      properties of veneering ceramics on the fracture load of layered ceria stabilized
      zirconia/alumina nanocomposite (Ce-TZP/A) single crowns. METHODS: Ce-TZP/A single
      crown frameworks (nanoZr) were veneered with 5 different veneering ceramics for
      zirconia (Cerabien ZR, IPS e.max, Triceram, Vintage ZR, VM9). In addition,
      veneering ceramics for alumina (Allux) and for the metal-ceramic technique
      (Reflex) were included in order to cover a wide range of coefficients of thermal
      expansion. Fracture load of the crowns was assessed in a shear test (n=10). Glass
      transition temperatures (T(g)) of the ceramics as well as the coefficients of
      thermal expansion of the ceramics (alpha(veneer)) and Ce-TZP/A (alpha(core))
      between 25 and 500 degrees C were determined (n=6). RESULTS: Fracture load ranged
      from 574.0+/-97.1N (IPS e.max) to 1009.6+/-150.0N (VM9). Deltaalpha=alpha(core)
      alpha(veneer) and DeltaT=T(g)-25 degrees C (DeltaT in K) were calculated. The
      fracture load was strongly correlated to Deltaalpha DeltaT with a maximum at
      Deltaalpha DeltaT approximately 580 x 10(-6). SIGNIFICANCE: The overall fracture
      load of veneered Ce-TZP/A crowns is correlated to the thermal properties of the
      respective veneering ceramic.

PMID- 18804857
TI  - Electrolytic deposition of lithium into calcium phosphate coatings.
AB  - OBJECTIVES: Lithium ions stimulate the Wnt signaling pathway and the authors
      previously demonstrated that lithium enhances the proliferation of tissue
      cultured human mesenchymal stem cells. The aim of this study was to prepare and
      characterize a calcium phosphate/lithium coating by means of electrolytic
      deposition. It was hypothesized that the hybrid coatings would enhance the
      proliferation of MG63 osteoblast-like cells in vitro. METHODS: Calcium phosphate
      coatings were electrolytically deposited in electrolytes containing 0, 0.5 and
      5g/L lithium chloride, respectively. They were characterized by scanning electron
      microscopy, X-ray diffraction, and Fourier transform infrared spectroscopy. The
      coating thickness, lithium content and release profile were also measured. The
      cell attachment and cell-doubling index of MG63 cells on these coatings were
      determined through a Cell Counting Kit-8. RESULTS: Lithium inhibited calcium
      phosphate deposition in a dose-dependent manner. Both crystallinity and thickness
      of the coatings were reduced with increasing lithium concentration in the
      electrolyte. The incorporation of lithium was 2.2 and 5.5microg/mg, respectively.
      The hybrid coatings demonstrated a burst lithium release within half an hour upon
      immersion into simulated physiological solution. Both attachment and early
      proliferation of MG63 cells on these hybrid coatings were enhanced. SIGNIFICANCE:
      These results suggest that lithium can be effectively incorporated into calcium
      phosphate coatings. The incorporation of lithium interferes with calcium
      phosphate deposition; however, it enhances the biocompatibility of the coatings.

PMID- 18804858
TI  - Sediment redox tracers in Strait of Georgia sediments--can they inform us of the
      loadings of organic carbon from municipal wastewater?
AB  - Organic carbon composition and redox element (Mn, Cd, U, Re, Mo, SigmaS, AVS)
      distributions are examined in seven 210Pb-dated box cores collected from the
      Strait of Georgia, British Columbia to evaluate the potential for redox elements
      to reveal impacts of anthropogenic loadings of labile organic carbon to
      sediments. In particular, the cores have been collected widely including regions
      far from local anthropogenic inputs and from locations within the zone of
      influence of two municipal outfalls where sediments are exposed to enhanced
      organic loadings from outfalls. We find a wide natural range in organic carbon
      forcing within the basin sediments generally reflected as Mn enrichments near the
      surface in cores exhibiting slow organic oxidation and sulphide, Cd, Mo, U and Re
      enrichments in cores exhibiting higher organic oxidation rates. Concentration
      profiles for redox elements or organic carbon are misleading by themselves, as
      they are influenced strongly by sediment porosity and sedimentation rate, and the
      organic matter remaining in sediment cores is predominantly recalcitrant. Fluxes
      of redox elements together with rates of organic metabolism estimated from
      sedimentation rates provide a better picture of the organic forcing. One core,
      GVRD-3, collected within the zone of influence of the Iona municipal outfall (0.5
      km away), exhibits the highest organic carbon oxidation rates, enhanced Ag fluxes
      in the sediment surface mixed layer and altered delta15N composition, all of
      which implicate outfall particulates. Cd is also elevated in the GVRD-3 surface
      sediments, but evidence points to contamination and not redox forcing supporting
      this observation. Uranium also shows enrichment at sites near the outfalls,
      possibly in response to enhanced microbial metabolism. Predominantly these cores
      exhibit a wide natural range of organic carbon fluxes and organic carbon
      oxidation rates, supported by fluxes of marine and terrigenous organic carbon,
      within which it is difficult to identify any significant impact from municipal
      outfall organic carbon.

PMID- 18804859
TI  - Reduced acute inflammatory responses to microgel conformal coatings.
AB  - Implantation of synthetic materials into the body elicits inflammatory host
      responses that limit medical device integration and biological performance. This
      inflammatory cascade involves protein adsorption, leukocyte recruitment and
      activation, cytokine release, and fibrous encapsulation of the implant. We
      present a coating strategy based on thin films of poly(N-isopropylacrylamide)
      hydrogel microparticles (i.e. microgels) cross-linked with poly(ethylene glycol)
      diacrylate. These particles were grafted onto a clinically relevant polymeric
      material to generate conformal coatings that significantly reduced in vitro
      fibrinogen adsorption and primary human monocyte/macrophage adhesion and
      spreading. These microgel coatings also reduced leukocyte adhesion and expression
      of pro-inflammatory cytokines (TNF-alpha, IL-1beta, MCP-1) in response to
      materials implanted acutely in the murine intraperitoneal space. These microgel
      coatings can be applied to biomedical implants as a protective coating to
      attenuate biofouling, leukocyte adhesion and activation, and adverse host
      responses for biomedical and biotechnological applications.

PMID- 18804860
TI  - The effect of lactose-conjugated silk biomaterials on the development of
      fibrogenic fibroblasts.
AB  - Surface properties of implanted biomaterials can cause fibrotic tissue reactions
      by stimulating differentiation of host fibroblasts into contractile
      myofibroblasts. Silk fibroin (SF) protein has been used as biomaterial in pure
      and blended form. however, its effect on myofibroblast differentiation remains
      elusive. We here conjugated SF with lactose using cyanuric chloride as coupling
      spacer. NMR spectroscopy and the conjugates ability to agglomerate Abrus
      precatorius agglutinin verified efficient conjugation. Two-dimensional films and
      three-dimensional scaffolds produced from pure and lactose-conjugated SF
      solutions were tested as culture substrates for subcutaneous fibroblasts and
      myofibroblasts. Lactose-conjugated SF substrates mediated higher adhesion,
      proliferation and viability of fibroblastic cells than pure SF. This SF film
      composition promotes better attachment of fibroblasts than myofibroblasts. Pro
      fibrotic cytokine TGFbeta1 was ineffective in inducing fibroblast-to
      myofibroblast differentiation on such substrates. Pre-differentiated
      myofibroblasts lost their contractile phenotype within a few days of being
      cultured on lactose-conjugated SF. Myofibroblast differentiation was also
      suppressed by growth in three-dimensional lactose-conjugated SF scaffolds that,
      however, support population with fibroblasts. We propose that this biomaterial
      will promote tissue integration without causing a fibrotic host reaction.

PMID- 18804861
TI  - Viscoelastic adhesive mechanics of aldehyde-mediated soft tissue sealants.
AB  - Soft tissue sealants generally sacrifice adhesive strength for biocompatibility,
      motivating the development of materials which interact with tissue to a
      predictable and controllable extent. Crosslinked hydrogels comprising aminated
      star polyethylene glycol and high molecular weight dextran aldehyde polymers
      (PEG:dextran) display aldehyde-mediated adhesion and readily tunable reactivity
      with soft tissue ex-vivo. Evaluation of PEG:dextran compositional variants
      revealed that the burst pressure of repaired intestinal wounds and the extent of
      material-induced tissue deformation both increase nonlinearly with formulation
      aldehyde content and are consistently within the desired range established by
      traditional sealants. Adhesive test elements featuring PEG:dextran and intestinal
      tissue exhibited considerable viscoelasticity, prompting use of a standard linear
      solid (SLS) model to describe adhesive mechanics. Model elements were accurately
      represented as continuous functions of PEG:dextran chemistry, facilitating
      prediction of adhesive mechanics across the examined range of compositional
      formulations. SLS models of traditional sealants were also constructed to allow
      general correlative analyses between viscoelastic adhesive mechanics and metrics
      of sealant performance. Linear correlation of equilibrium SLS stiffness to
      sealant-induced tissue deformation indicates that dense adhesive crosslinking
      restricts tissue expansion, while correlation of instantaneous SLS stiffness to
      burst pressure suggests that the adhesive stress relaxation capacity of
      PEG:dextran enhances their overall performance relative to traditional sealants.

PMID- 18804862
TI  - Strontium modified biocements with zero order release kinetics.
AB  - Strontium-substituted beta-TCP with the general formula Ca((3-x))Sr(x)(PO(4))(2)
      (0<x<1) was synthesized by calcination of powder mixtures with the appropriate
      stoichiometry and reacted with acidic monocalcium phosphate monohydrate (MCPM) to
      form a cementitious matrix of secondary calcium phosphates. The use of Sr
      substituted beta-TCP as a reactant not only induced strontium substitution in the
      setting products but surprisingly it also favoured the formation of monetite
      (CaHPO(4)) as setting product, whereas Sr-free cements set to brushite
      (CaHPO(4).2H(2)O). Release experiments under dynamic conditions for up to 15 days
      revealed the release of Sr(2+) ions at dose ranges of 12-30 ppm with zero order
      release kinetic. Cement cytocompatibility was investigated by culturing human
      osteoblast cell line hFOB1.19 on cement surfaces whereas Sr-containing cements
      were as good as Sr-free cements in providing a template for cell growth and
      function.

PMID- 18804863
TI  - Production of monoclonal antibodies specific to major outer membrane protein of
      Edwardsiella tarda.
AB  - Edwardsiella tarda is an important cause for hemorrhagic septicemia in fish and
      gastro and extra-intestinal infections in humans. Monoclonal antibodies (MAbs)
      were produced against outer membrane proteins (OMPs) of E. tarda ET-7, isolated
      from diseased snakehead (Ophiocephalus punctatus). Two stable hybridoma clones,
      designated as 3F10 and 2C3 MAbs were found to be potentially specific for E.
      tarda by indirect enzyme linked immunosorbent assay (ELISA). These MAbs
      recognized major immunogenic OMP band at 44kDa in Western blotting. Both MAbs
      belonged to the IgG1 isotype and recognized different epitopes of OMP as seen by
      competitive ELISA. These MAbs strongly reacted with all 17 isolates of E. tarda
      used in our study by indirect ELISA and Western blotting. Interestingly, no
      reaction was observed with the reference strain of E. tarda (MTCC 2400). The
      sensitivity of 3F10 MAb to detect whole cells of E. tarda was up to a level of
      1x10(4)CFU/ml in indirect ELISA. No cross-reactivity of MAbs were seen with
      Escherichia coli, Salmonella arizonae, Pseudomonas fluorescens, Aeromonas
      hydrophila, Vibrio cholerae, Flavobacterium ferrugineum and Mycobacterium
      tuberculosis. These MAbs could be used for specific detection of E. tarda
      infection in fish by immunoassays.

PMID- 18804864
TI  - Brominated flame retardants and organochlorines in the European environment using
      great tit eggs as a biomonitoring tool.
AB  - Large-scale studies are essential to assess the emission patterns and spatial
      distribution of organohalogenated pollutants (OHPs) in the environment. Bird eggs
      have several advantages compared to other environmental media which have
      previously been used to map the distribution of OHPs. In this study, large-scale
      geographical variation in the occurrence of OHPs, such as polychlorinated
      biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) and organochlorine
      pesticides (OCPs), was investigated throughout Europe using eggs of a terrestrial
      residential passerine species, the great tit (Parus major). Great tit eggs from
      22 sampling sites, involving urban, rural and remote areas, in 14 European
      countries were collected and analysed (5-8 eggs per sampling site). The
      environmentally most important congeners/compounds of the analysed pollutants
      were detectable in all sampling locations. For PCBs, PBDEs and OCPs, no clear
      geographical contamination pattern was found. Sum PCB levels ranged from 143 ng/g
      lipid weight (lw) to 3660 ng/g lw. As expected, PCB concentrations were
      significantly higher in the sampled urban compared to the remote locations.
      However, the urban locations did not show significantly higher concentrations
      compared to the rural locations. Sum PBDEs ranged from 4.0 ng/g lw to 136 ng/g
      lw. PBDEs were significantly higher in the urbanized sampling locations compared
      to the other locations. The significant, positive correlation between PCB and
      PBDE concentrations suggests similar spatial exposure and/or mechanisms of
      accumulation. Significantly higher levels of OCPs (sum OCPs ranging from 191 ng/g
      lw to 7830 ng/g lw) were detected in rural sampling locations. Contamination
      profiles of PCBs, PBDEs and OCPs differed also among the sampling locations,
      which may be due to local usage and contamination sources. The higher variance
      among sampling locations for the PCBs and OCPs, suggests that local contamination
      sources are more important for the PCBs and OCPs compared to the PBDEs. To our
      knowledge, this is the first study in which bird eggs were used as a monitoring
      tool for OHPs on such a large geographical scale.

PMID- 18804865
TI  - Environmental impact and human exposure to PCBs in Guiyu, an electronic waste
      recycling site in China.
AB  - PCB levels in fish (collected from local rivers), atmosphere and human milk
      samples have been studied to determine the exposure levels of PCBs for local
      residents and e-waste workers in Guiyu, a major electronic waste scrapping center
      in China. The source appointment and correlation analyses showed that homologue
      composition of PCBs in 7 species of fish were consistent and similar to
      commercial PCBs Aroclor 1248. PCB levels in air surrounding the open burning site
      were significantly higher than those in residential area. Inhalation exposure
      contributed 27% and 93% to the total body loadings (the sum of dietary and
      inhalation exposure) of the local residents, and e-waste workers engaged in open
      burning respectively. Total PCB concentrations in human milk ranged from N.D. to
      57.6 ng/g lipid, with an average of 9.50 ng/g lipid. The present results
      indicated that commercial PCBs derived from e-waste recycling are major sources
      of PCBs accumulating in different environmental media, leading to the
      accumulation of high chlorinated biphenyls in human beings.

PMID- 18804866
TI  - Stress and innate immunity in carp: corticosteroid receptors and pro-inflammatory
      cytokines.
AB  - The stress hormone cortisol is deeply involved in immune regulation in all
      vertebrates. Common carp (Cyprinus carpio L.) express four corticoid receptors
      that may modulate immune responses: three glucocorticoid receptors (GR); GR1,
      with two splice variants (GR1a and GR1b), GR2 and a single mineralocorticoid
      receptor (MR). All receptors are expressed as of 4 days post-fertilization and
      may thus play a critical role in development and functioning of the adult immune
      system. Immune tissues and cells predominantly express mRNA for GRs compared to
      mRNA for the MR. Three-dimensional protein structure modeling predicts, and
      transfection assays confirm that alternative splicing of GR1 does not influence
      the capacity to induce transcription of effector genes. When tested for cortisol
      activation, GR2 is the most sensitive corticoid receptor in carp, followed by the
      MR and GR1a and GR1b. Lipopolysacharide (LPS) treatment of head kidney phagocytes
      quickly induces GR1 expression and inhibits GR2 expression. Cortisol treatment in
      vivo enhances GR1a and MR mRNA expression, but only mildly, and cortisol
      treatment in vitro does not affect receptor expression of phagocytes. Cortisol
      has no direct effect on the LPS-induced receptor profile. Therefore, an immune
      rather than a stress stimulus regulates GR expression. Cortisol administered at
      stress levels to phagocytes in vitro significantly inhibits LPS-induced
      expression of the pro-inflammatory cytokines tumor necrosis factor alpha (TNF
      alpha) and interleukin-12 (IL-12) (subunit p35) and of inducible nitric oxide
      synthase (iNOS) expression. A physiologically differential function for GR1 and
      GR2 in the immune response of fish to infection is indicated.

PMID- 18804867
TI  - Lactobacillus casei potentiates induction of oral tolerance in experimental
      arthritis.
AB  - Probiotics have been shown to exert beneficial effects on modulation of diverse
      diseases. However, no information is available for the effect of probiotics in
      the induction of oral tolerance in autoimmune diseases. The main purpose of this
      study was to elucidate whether Lactobacillus casei (L. casei) affect the
      induction of oral tolerance in experimental rheumatoid arthritis (RA). Type II
      collagen (CII) alone or together with L. casei was orally administered into
      collagen-induced arthritis (CIA) rats, and its effects on the clinical and
      histopathological aspects of RA were investigated. Co-administration of L. casei
      with CII more effectively suppressed clinical symptoms, paw swelling, lymphocyte
      infiltration and destruction of cartilage tissues of experimental arthritis than
      the rats treated with CII alone. The enhanced therapeutic efficacy was associated
      with an increase in anti-inflammatory cytokines (IL-10 and TGF-beta) while
      decreasing pro-inflammatory cytokines (IL-1beta, IL-2, IL-6, IL-12, IL-17, IFN
      gamma and TNF-alpha). Co-administration of L. casei with CII more effectively
      suppressed CII-reactive T cell proliferation and the levels of Th1-type IgG
      isotypes (IgG2a and IgG2b), while up-regulating Foxp3 expression levels and the
      population of Foxp3(+) CD4(+) T cells. Our study provides evidence that L. casei
      could potentiate antigen-specific oral tolerance and suppress Th1-type immune
      responses of arthritic inflammation.

PMID- 18804868
TI  - Safety of overnight orthokeratology for myopia: a report by the American Academy
      of Ophthalmology.
AB  - OBJECTIVE: To review the published literature to evaluate the safety of overnight
      orthokeratology (OOK) for the treatment of myopia. METHODS: Repeated searches of
      peer-reviewed literature were conducted in PubMed (limited to the English
      language) and the Cochrane Central Register of Controlled Trials (no language
      limitations) for 2005, 2006, and 2007. The searches yielded 495 citations. The
      panel reviewed the abstracts of these articles and selected 79 articles of
      possible clinical relevance for review. Of these 79 full-text articles, 75 were
      determined to be relevant to the assessment objective. RESULTS: No studies were
      rated as having level I evidence. Two premarket applications to the Food and Drug
      Administration were rated as having level II evidence. There were 2 studies rated
      as having level II evidence. The main source of reports of adverse events
      associated with OOK was 38 case reports or noncomparative case series (level III
      evidence). CONCLUSIONS: The prevalence and incidence of complications associated
      with OOK have not been determined. Complications, including more than 100 cases
      of infectious keratitis resulting from gram-positive and gram-negative bacteria
      and Acanthamoeba, have been described in case reports and case series
      representing observations in undefined populations of OOK users. Data collection
      was nonstandard. Risk factors for various complications cannot be determined.
      Because OOK puts patients at risk for vision-threatening complications they may
      not encounter otherwise, sufficiently large well-designed cohort or randomized
      controlled studies are needed to provide a more reliable measure of the risks of
      treatment and to identify risk factors for complications. Overnight
      orthokeratology for slowing the progression of myopia in children also needs well
      designed and properly conducted controlled trials to investigate efficacy.
      Because of variations in orthokeratology practice, a wide margin of safety should
      be built into OOK regimens. FINANCIAL DISCLOSURE(S): Proprietary or commercial
      disclosure may be found after the references.

PMID- 18804869
TI  - Should we change the definition of fever in nosocomial infection surveillance?

PMID- 18804870
TI  - Weather and notified Campylobacter infections in temperate and sub-tropical
      regions of Australia: an ecological study.
AB  - BACKGROUND: The relationship between weather and food-borne diseases has been of
      great concern recently. However, the impact of weather variations on food-borne
      disease may vary in different areas with various geographic, weather and
      demographic characteristics. This study was designed to quantify the relationship
      between weather variables and Campylobacter infections in two Australian cities
      with different local climatic conditions. METHODS: An ecological-epidemiological
      study was conducted, using weekly disease surveillance data and meteorological
      data, over the period 1990-2005, to quantify the relationship between maximum and
      minimum temperatures, rainfall, relative humidity and notifications of
      Campylobacter infections in Adelaide, with a temperate Mediterranean climate, and
      Brisbane, with a sub-tropical climate. Spearman correlation and time-series
      adjusted Poisson regression analyses were performed taking into account
      seasonality, lag effects and long-term trends. RESULTS: The results indicate that
      weekly maximum and minimum temperatures were inversely associated with the weekly
      number of cases in Adelaide, but positively correlated with the number of cases
      in Brisbane, with relevant lagged effects. The effects of rainfall and relative
      humidity on Campylobacter infection rates varied in the two cities. CONCLUSION:
      Weather might have different effect on Campylobacter infections in different
      cities. Further studies are needed for a better understanding of these
      relationships for they may indicate epidemiologic factors important for control
      of these infections.

PMID- 18804871
TI  - Spinal infection caused by ESBL-producing Klebsiella pneumoniae treated with
      temocillin.
AB  - A case of cervical epidural abscess in a 63-year-old woman with a complex
      gastrointestinal surgical history is reported. The presenting symptom was neck
      pain, and blood analysis demonstrated raised erythrocyte sedimentation rate and C
      reactive protein. MR imaging of the cervical spine revealed cervical discitis,
      osteomyelitis, and epidural collection. An ESBL-producing strain of Klebsiella
      pneumoniae, isolated from a previous episode of bacteraemia, was the causative
      organism. Surgical treatment was not possible and initial carbapenem therapy was
      aborted due to development of neutropaenia, and treatment continued with an
      extended course of temocillin. After 12 weeks of antibiotics the patient was pain
      free with radiological improvement and resolution of blood markers of infection.

PMID- 18804872
TI  - Infant temperament and information processing in a visual categorization task.
AB  - This study investigates the relation between temperament and information
      processing in 7-month-old infants. Infant temperament was assessed on multiple
      dimensions, using mothers' ratings on the Infant Behavior Questionnaire (IBQ).
      Information processing was measured during a paired-comparison visual
      categorization task. Infants (N=50) were familiarized with five different pairs
      of visual stimuli from one category, followed by two test trials, each
      contrasting a novel familiar-category item with a novel out-of-category item
      (animals vs. vehicles). Drop-out rate in this task was within a normal range
      (21%). No differences in temperament were found between completers and non
      completers, but high reactivity to novelty and low motor activity were positively
      correlated with the strength of infants' familiarization response. Group
      comparisons between infants scoring high and low on these two dimensions of
      temperament confirmed this general finding: infants high on distress to novelty
      and low on motor activity showed stronger familiarization responses. Furthermore,
      infants scoring low on motor activity showed a stronger categorization response
      than highly active infants. This study provides evidence that performance in a
      cognitive categorization task and dimensions of infant temperament are
      systematically related during the second half of the first year of life.
      Implications for cognitive research with infants of this age-range will be
      discussed.

PMID- 18804873
TI  - The reliability and validity of the Infant Behavior Questionnaire-Revised.
AB  - The reliability and validity of the Infant Behavior Questionnaire-Revised was
      examined in a sample of 6-month-old infants and their parents. One hundred and
      fifteen mothers and 79 fathers completed the IBQ-R and a measure of depression
      and 98 infants participated in a laboratory assessment of temperament. Internal
      consistency reliability was adequate for all 14 IBQ-R subscales for both mothers
      and fathers and inter-rater reliability of mother and father reports was
      demonstrated for 11 of 14 subscales. Convergent validity was established between
      observed fear and mother reported fear and father reported approach. Parent
      depression and infant gender were examined as moderators of the concordance
      between parent reported and observed temperament. As predicted, concordance was
      higher when parents reported low versus high symptoms of depression. Infant
      gender did not alter concordance.

PMID- 18804874
TI  - Comparison of 2-year effects of once and twice weekly water exercise on
      activities of daily living ability of community dwelling frail elderly.
AB  - Previous research suggests that water exercise improves the activities of daily
      living (ADL) ability of the frail elderly, but the specific frequency and
      intensity of such programs is unclear. This study aims at comparing the effects
      of once- and twice-weekly water exercise on the ADL ability of frail elderly
      receiving nursing care for 2 years. The design is a prospective randomized
      longitudinal study. Participants were assigned to two different exercise groups
      (Group 1 and Group 2). Group 1 participated in a 60-min exercise session once a
      week, for 2 years, while Group 2 attended the session twice a week. Exercise
      sessions were divided into a 10-min warm-up on land and 50 min of exercise in
      water. The 50-min water exercise program consisted of 20 min walking, 10 min ADL
      exercise, 10 min stretching and strength exercises, and 10 min relaxation in
      water. ADL ability and lower muscle strength were measured before the beginning
      of exercise and 6 months, 1 year, and 2 years after the program had started.
      Significant group differences occurred for bathing transfer and stair climbing at
      the 2-year measurement. These results suggested that at least twice-weekly water
      exercise was necessary to maintain the ADL ability and KEX of the frail elderly
      during the 1-year water exercise period and for one additional year afterward.

PMID- 18804875
TI  - Cardiac multi-detector CT: its unique contribution to cardiology practice.
AB  - Medical practice is moving fast towards non-invasive and non-surgical disease
      management. While significant progress has been made with coronary artery disease
      prevention, MDCT stands as an ideal non-invasive tool for its progression. It
      accurately assesses both arterial lumen and wall disease. Although the main
      concern of current cardiology practice is the coronary stenotic disease, arterial
      wall calcification itself may significantly contribute to patients' symptoms.
      Thus, in addition to the beneficial use of MDCT in patients with mild to moderate
      risk for coronary disease, the unique information it provides on wall disease may
      assist the management of symptomatic patients with no flow-limiting lesions.

PMID- 18804876
TI  - Left atrial dyssynchrony assessed by strain imaging in predicting future
      development of atrial fibrillation in patients with heart failure.
AB  - BACKGROUND: The clinical and echocardiographic parameters associated with the
      risk of developing new onset atrial fibrillation (AF) in congestive heart failure
      (CHF) have not been studied comprehensively. We determined if dyssynchronous left
      atrial (LA) lengthening and contraction predicted future development of new onset
      AF in patients with CHF. METHODS: One hundred fifty-eight patients who were
      admitted for CHF without past or current AF were evaluated. We measured the time
      to peak velocity and time to peak strain with reference to the QRS complex during
      ventricular systole (reservoir) and late diastole (atrial contraction) in mid
      portion of 4 LA walls. Dyssynchronous atrial lengthening and contraction (atrial
      dyssynchrony) was defined as the standard deviation of each parameter. RESULTS:
      New onset AF developed in 21 patients (13.3%) after a mean follow-up of 43+/-15
      months. Based on univariate Cox analysis, older age, larger LA dimension and
      volume index, lower LA fractional shortening, and the presence of atrial
      dyssynchrony were associated with new onset AF. In multivariate Cox analysis,
      atrial dyssynchrony based on strain (>39 ms, HR 10.0, p=0.003) and LA size (> or
      =45 mm, HR 4.3, p=0.016) were independent predictors of new onset AF in CHF.
      CONCLUSIONS: We demonstrated that atrial dyssynchrony based on strain is the
      strongest univariate and multivariate predictor for new onset AF in hospitalized
      patients with CHF.

PMID- 18804877
TI  - Sirolimus-eluting stent implantation in small coronary arteries: a three
      dimensional intravascular ultrasound study from the SIRIUS trial.
AB  - AIM: To assess the efficacy of the sirolimus-eluting stent when implanted in
      smaller caliber vessels using three-dimensional intravascular ultrasound (IVUS)
      analysis. METHODS: One hundred and twenty-three patients (69 sirolimus-coated Bx
      Velocity and 54 control) who underwent successful three-dimensional IVUS at
      follow up comprised this IVUS substudy from the SIRIUS (SIRolImUS-coated Bx
      Velocity stent in the treatment of patients with de novo coronary artery lesions)
      population. To evaluate the impact of vessel size, 2 groups were created using
      QCA reference vessel diameter (RVD; large vessel group: RVD>/=2.75 mm and small
      vessel group: RVD<2.75 mm). RESULTS: Sirolimus-eluting stents significantly
      reduced neointimal hyperplasia by the same relative magnitude within the stent in
      small vessels as well as in large vessels. Although sirolimus-eluting stents had
      favorable effects on lumen area at stent edges in larger vessels, the effect was
      less in smaller vessels, especially at the proximal edge. IVUS-detected adverse
      vessel response, such as late-acquired incomplete apposition, did not increase in
      smaller vessels even with relatively higher dose exposure. CONCLUSION: Sirolimus
      eluting stents showed inhibition of neointimal hyperplasia in small vessels
      compared to bare metal stents with no increase of vascular complications.

PMID- 18804878
TI  - Differential impact of metabolic syndrome on arterial stiffness and wave
      reflections: focus on distinct definitions.
AB  - BACKGROUND: Arterial stiffness and wave reflections are independent predictors of
      cardiovascular disease. Metabolic syndrome (MS) is related to increased aortic
      stiffness in several populations. However, it is unclear whether the association
      of MS with aortic stiffness differs according to the considered definition.
      Moreover, data regarding the association of wave reflections with MS are limited.
      For this purpose, we examined the relationship of arterial stiffness and wave
      reflections with MS by using four current definitions and a score. METHODS: We
      studied 732 never treated, non-diabetic hypertensive patients. Metabolic syndrome
      was defined by Adult Treatment Panel III, American Heart Association, World
      Health Organization (WHO), International Diabetes Federation criteria and MS
      (GISSI) score. Arterial stiffness was assessed by measuring carotid-femoral pulse
      wave velocity (PWVc-f). Heart rate-corrected augmentation index (AIx(75)) was
      estimated as a measure of wave reflections. RESULTS: By all definitions,
      hypertensive patients with MS had higher PWVc-f compared to hypertensives without
      MS. On the contrary, no significant difference was observed in AIx(75) between
      patients with and those without MS except when MS was defined by WHO criteria. An
      independent association emerged between PWVc-f and GISSI score and MS components
      (p=0.038 and 0.033 respectively) in patients with MS, after adjustment for age,
      gender, LDL cholesterol and smoking. Nevertheless, after further adjustment for
      systolic blood pressure or body mass index, the strength of this association was
      reduced to a non-significant level. CONCLUSION: Arterial stiffness is increased
      in patients with metabolic syndrome irrespective of the definition criteria. On
      the contrary, metabolic syndrome has no effect on wave reflections, except when
      this is defined by WHO criteria. Regarding the high prognostic significance of
      both arterial stiffness and wave reflections, these findings might have important
      clinical implications.

PMID- 18804879
TI  - Clinical factors affecting serum potassium concentration in cardio-renal
      decompensation syndrome.
AB  - BACKGROUND: Renin-angiotensin-aldosterone system (RAAS) inhibitors are currently
      indispensable for the treatment of heart failure. It is well known that
      hyperkalemia is likely to occur in renal failure; however, it has not yet been
      clarified how the serum potassium concentration changes as heart failure
      progresses. Currently, the cardio-renal decompensation syndrome holds that the
      serum potassium concentration is altered similarly by both heart failure and
      renal failure; however, there are no definitive reports on this. In order to use
      RAAS inhibitors more safely and effectively in heart failure, it is necessary to
      understand the factors affecting serum potassium concentration in the clinical
      setting. METHODS AND RESULTS: We examined the clinical factors affecting serum
      potassium concentration in 1035 consecutive patients with cardiovascular disease
      who were hospitalized in our institution. Multiple regression analysis showed
      that the independent factors associated with an elevated serum potassium
      concentration were renal insufficiency evaluated by estimated glomerular
      filtration rate (eGFR) (P<0.0001), diabetes mellitus evaluated by HbA(1c)
      (P=0.0005) and the use of RAAS inhibitors (P=0.0010). The independent factors
      associated with a decreased serum potassium concentration were mean blood
      pressure (P<0.0001), heart failure evaluated by log BNP (P=0.0164) and the use of
      diuretics (P=0.0232). CONCLUSIONS: The serum potassium concentration decreases
      with the severity of heart failure if renal function is preserved. From the
      perspective of potassium homeostasis, we could use the RAAS inhibitors more
      aggressively in patients with heart failure who do not have renal failure.

PMID- 18804880
TI  - Magnetic resonance reveals long-term sequelae of apical ballooning syndrome.
AB  - BACKGROUND: The presence of small areas of necrosis has been occasionally
      reported immediately following apical ballooning syndrome (ABS). However, their
      persistence at later stages and impact on long-term prognosis are currently
      unknown. METHODS: Twenty consecutive patients admitted for ABS between 2004 and
      2007 were prospectively evaluated. Demographic, clinical, angiographic, and
      echocardiographic data were collected during hospital admission. At a mean of
      11+/-9 months follow-up, a contrast enhanced cardiac magnetic resonance (ce-CMR)
      study was performed in 17 cases. The presence of hyperenhancement on ce-CMR
      images, reflecting irreversible myocardial damage, was recorded by two
      independent observers. RESULTS: Two of 3 patients with hyperenhancement on ce-CMR
      images presented in worse condition, including pulmonary edema or cardiogenic
      shock, compared to just 2 of 14 patients without hyperenhancement (p=0.052).
      Segmental wall motion substantially improved in both of those cases; the third
      patient continued to have hypokinesis in a segment showing hyperenhancement.
      Segmental wall motion also significantly improved in all patients with no
      hyperenhancement. At a mean of 20+/-12 months follow-up, no deaths or major
      adverse cardiac events were documented among patients with or without
      hyperenhancement. CONCLUSIONS: Despite segmental wall motion recovery, an area of
      irreversible myocardial damage can sometimes be identified long after ABS.
      However, in this limited series of patients, the presence of scar, even when
      presenting with heart failure and a higher troponin release, was not associated
      with adverse long-term outcomes as compared to patients with intact myocardium.

PMID- 18804881
TI  - Differences in determinants of left ventricular mass assessed by cardiac magnetic
      resonance imaging across subjects with and without previous symptomatic
      atherosclerotic disease.
AB  - BACKGROUND: Most previous studies on determinants of left ventricular (LV) mass
      have used echocardiography, which is less accurate than cardiac MRI (CMR).
      Furthermore, studies that used CMR to study the determinants of LV mass were
      performed in the general population. However, determinants may differ between
      those with and without previous symptomatic events. We studied the relation
      between atherosclerotic risk factors and LV mass in subjects free from cardiac
      disease, yet with and without atherosclerotic disease elsewhere. METHODS: A CMR
      was performed in 531 hypertensive subjects with clinically manifest extra-cardiac
      atherosclerotic disease or marked risk factors for atherosclerosis. In all
      subjects information on atherosclerotic risk factors was collected. Multivariable
      linear regression was used to study the relation of risk factors with LV mass.
      Interaction was evaluated with multiplicative interaction terms. RESULTS:
      Overall, male gender, weight, height, systolic blood pressure, albuminuria,
      current smoking, and a history of abdominal aortic aneurysm (AAA) were related to
      an increased LV mass. In subjects without a history of symptomatic
      atherosclerotic disease, gender, weight, height and systolic blood pressure were
      related to LV mass. In addition to these risk factors, albuminuria, current
      smoking and a history of AAA were related to LV mass in subjects with a history
      of symptomatic atherosclerotic disease. CONCLUSION: Our study points towards
      differences in risk factor relations across populations with and without
      symptomatic atherosclerotic disease. The observed relationship between
      cardiovascular risk factors and LV mass re-emphasizes the importance of adequate
      treatment of modifiable risk factors in the prevention of cardiovascular disease.

PMID- 18804882
TI  - The prognostic value of the heart rate response during exercise and recovery in
      patients with heart failure: influence of beta-blockade.
AB  - BACKGROUND: The heart rate increase during exercise (DeltaHR) and heart rate
      recovery (HRR) have demonstrated prognostic value in several investigations, but
      its application in the heart failure (HF) population is limited, particularly in
      a beta-blocked (BB) cohort. METHODS: Five-hundred and twenty subjects with HF
      underwent cardiopulmonary exercise testing to determine peak oxygen consumption
      (VO(2)), the minute ventilation/carbon dioxide production (VE/VCO(2)) slope,
      DeltaHR and HRR at 1 min (HRR(1)). RESULTS: There were 79 cardiac-related deaths
      during the tracking period. A HRR(1) threshold of </>or=16 beats/min was a
      significant prognostic marker in the overall group (hazard ratio: 4.6, 95% CI:
      2.8-7.5, p<0.001) as well as no-BB (hazard ratio: 9.1, 95% CI: 4.1-20.2, p<0.001)
      and BB (hazard ratio: 2.9, 95% CI: 1.6-5.4, p<0.001) subgroups. The DeltaHR was a
      significant univariate predictor in the overall group and no-BB subgroup only.
      Multivariate Cox regression analysis revealed HRR(1) was the strongest prognostic
      marker (chi-square: 39.9, p<0.001). The VE/VCO(2) slope (residual chi-square:
      21.8, p<0.001) and LVEF (residual chi-square: 9.6, p=0.002) were also retained in
      the regression. CONCLUSIONS: These results indicate that HRR maintains prognostic
      value in HF irrespective of BB use. The routine inclusion of HRR in the
      prognostic assessment of patients with HF may be warranted.

PMID- 18804883
TI  - Rocuronium-induced coronary vasospasm--"Kounis syndrome".
AB  - A 49-year-old male became hypotensive, bradycardic, and suffered myocardial
      injury during induction of anesthesia with lidocaine, propofol, and rocuronium in
      the operating room. Coronary arteriography revealed coronary vasospasm in
      coronary arteries otherwise free of disease. In the ICU, the patient was again
      administered rocuronium for a procedure with subsequent hypotension, bradycardia,
      and ST elevation on telemetry that resolved with administration of
      diphenhydramine and hydrocortisone. An allergic reaction to rocuronium with
      coronary vasospasm is suspected, suggestive of the Type 1 variant of Kounis
      syndrome. This is the first report to describe a case of rocuronium-induced Type
      1 Kounis syndrome.

PMID- 18804884
TI  - Nanobiocatalysis and its potential applications.
AB  - Nanobiocatalysis, in which enzymes are incorporated into nanostructured
      materials, has emerged as a rapidly growing area. Nanostructures, including
      nanoporous media, nanofibers, carbon nanotubes and nanoparticles, have manifested
      great efficiency in the manipulation of the nanoscale environment of the enzyme
      and thus promise exciting advances in many areas of enzyme technology. This
      review will describe these recent developments in nanobiocatalysis and their
      potential applications in various fields, such as trypsin digestion in proteomic
      analysis, antifouling, and biofuel cells.

PMID- 18804885
TI  - Streptococcus suis in retail markets: how prevalent is it in raw pork?
AB  - Streptococcus suis present in raw pork meats sold in local retail markets was
      enumerated by Most Probable Number (MPN)-PCR method. This method combined the
      conventional MPN technique with a specifically designed PCR assay based on the
      amplification of a 294-bp S. suis species-specific 16S rRNA gene sequence. A
      total of 78 raw pork lean meat samples purchased at two different supermarkets
      (Site A and B) and a wet market (Site C) were tested. Results indicated that S.
      suis could be detected from the enriched MPN tubes of all, except one, sample
      homogenates. The concentration of S. suis ranged from <3 to 4600 MPN/g of pork
      meat, with a total bacterial count (TBC) varying from 3.6 log to 7.4 log CFU/g.
      Statistical analyses indicated that pork meats purchased from the supermarket at
      Site B in summer contained significantly higher concentration of S. suis
      organisms than those from other retailers in any season. A significant
      correlation existed between log S. suis concentration and log TBC of the samples.
      This study revealed that raw pork meats available in local supermarkets or wet
      markets could contain S. suis at concentrations that were usually difficult to
      detect with traditional culture method. Field application of this method may
      contribute to a measurable evaluation, and thus the effective control, of human
      S. suis infection due to raw pork or pig carcass handling.

PMID- 18804886
TI  - Effects of different glycerol feeding strategies on S-adenosyl-l-methionine
      biosynthesis by P(GAP)-driven Pichia pastoris overexpressing methionine
      adenosyltransferase.
AB  - Methionine adenosyltransferase (MAT) was overexpressed within Pichia pastoris
      employing the promoter of glyceraldehyde-3-phosphate dehydrogenase gene (P(GAP)),
      to biosynthesize S-adenosyl-l-methionine (SAM). Effects of five glycerol feeding
      tactics on MAT activity were first investigated. Strategies A-C were based on
      limited feeding correlated with dissolved oxygen (DO) at 50.0%, 25.0% and 0.0%,
      respectively. For strategies D and E, unlimited supplementation was executed by
      pulsed feeding mode. Gradual decline (2-0%) (w:v) of the residual glycerol level
      was shown between any two pulses in strategy D, while a nearly stable content
      (2%) throughout fed-batch cultivation with strategy E. With shifting strategies A
      E in alphabetical order, gradual improvements of MAT activities were achieved,
      with the maximum of 9.05Ug(-1) dried biomass for strategy E, since the specific
      glycerol consumption rate (F(G)) ascended due to the elevated specific oxygen
      uptake rate (qO(2)). The success was ascribed to the enhancement of oxygen
      transfer rate (OTR), because 2% glycerol improved oxygen saturation content in
      broth (C*) and volumetric oxygen transfer coefficient (k(L)a). Strategy E also
      led to the highest values of ATP and biomass besides MAT. Consequently, the
      highest SAM yield and volumetric level were obtained at 0.058gg(-1) and 9.26gl(
      1), respectively.

PMID- 18804887
TI  - A trial of empowerment-based education in type 2 diabetes--global rather than
      glycaemic benefits.
AB  - We have assessed the effect of a structured, empowerment-based educational system
      ("LAY or "Look After Yourself") for patients with type 2 diabetes. A randomised
      controlled trial (RCT) was conducted, testing the system against standard
      support. Using 3 centres, 89 patients participated in the study. Outcome measures
      included glycated haemoglobin (HbA(1c)), body mass index (BMI) and a variety of
      quantitative psychological and educational measures. Assessment was made at 6
      months ("short-term") and 12 months ("long-term") post-intervention. The
      educational programme was associated with benefits in HbA(1c) levels (p=0.005),
      illness attitudes (p=0.04), and perceived treatment effectiveness (p=0.03) at 6
      months follow-up compared to controls. At 12 months however, only illness
      attitudes (p=0.01), and self-monitoring (p=0.002) showed benefit. A combined
      outcome measure showed positive benefit for the educational programme both at 6
      months (p=0.001) and 12 months (p=0.002). This structured educational programme,
      aimed at encouraging self-help, was associated with only limited benefits in
      glycaemic control, but there were significant educational and psychological
      benefits. Diabetes education should be regarded as having broad patient-based
      positive outcomes, and should not be expected to have lasting benefits on
      glycaemic control.

PMID- 18804888
TI  - Treatment of the hepatitis B virus and hepatitis C virus co-infection: still a
      challenge for the hepatologist.

PMID- 18804889
TI  - Hepcidin in the management of patients with mild non-hemochromatotic iron
      overload: Fact or fiction?

PMID- 18804890
TI  - Loss of Sept4 exacerbates liver fibrosis through the dysregulation of hepatic
      stellate cells.
AB  - BACKGROUND/AIMS: Septins are ubiquitous and multifunctional scaffold proteins
      involved in cytoskeletal organization, exocytosis and other cellular processes.
      We disclose the quiescent hepatic stellate cells (HSCs)-specific expression of a
      septin subunit Sept4 in the liver, and explore the significance of the septin
      system in liver fibrosis. METHODS: We analyzed the expression of alpha-smooth
      muscle actin (alpha-SMA), collagens and other markers in primary cultured HSCs
      derived from wild-type and Sept4(-/-) mice. We compared susceptibility of these
      mice to liver fibrosis induced by either carbon tetrachloride treatment, bile
      duct ligation or methionine/choline-deficient diet. Collagen deposition, the
      principal parameter of liver fibrosis, was quantified both histochemically
      (Masson's trichrome stain) and biochemically (hydroxyproline content). RESULTS:
      In vitro, Sept4 mRNA/protein was remarkably downregulated in HSCs through
      myofibroblastic transformation. Sept4(-/-) HSCs showed normal morphology and
      proliferation, while myofibroblastic transformation as monitored by the
      upregulation of alpha-SMA and collagen was accelerated compared to wild-type
      HSCs. In vivo, liver fibrosis was consistently more severe in Sept4(-/-) mice
      than in wild-type littermates in all of the three paradigms of hepatitis/liver
      fibrosis. CONCLUSIONS: These data concordantly indicate that the HSC-specific
      septin subunit Sept4 and perhaps the septin system are involved in the
      suppressive modulation of myofibroblastic transformation and fibrogenesis
      associated with liver diseases.

PMID- 18804892
TI  - Circulating plasma DNA as diagnostic biomarker in non-small cell lung cancer.
AB  - OBJECTIVES: The presence of circulating DNA in plasma of patients with malignant
      neoplasm has been a known fact for over 30 years. Since then, the concentration
      of free circulating plasma DNA has been studied as well as the genetic
      alterations and epigenetic alterations of tumour DNA of patients that suffer from
      various types of tumours. The analysis of circulating plasma DNA may be a useful
      marker to get an early diagnosis on malignant neoplasms. This study has been
      specifically designed to validate the quantification of circulating DNA in order
      to design a test useful for the early identification of non-small cell lung
      cancer patients and the monitoring of lung cancer progression. A second aim of
      this work is the sensibility and specificity evaluation of such method for future
      applications. METHODS: The quantity of plasma DNA was determined using
      quantitative Real-Time PCR with amplification of the human telomerase reverse
      transcriptase (hTERT) gene in 151 patients that suffer from lung cancer and 79
      healthy controls. The performance of the test was evaluated with a ROC curve. The
      relationship between the DNA concentration and main demographic, clinical and
      pathological variables was examined with logistic regression models as well as
      multiple linear regression models. RESULTS: The concentration of circulating
      plasma DNA was about four times higher in patients with lung cancer with respect
      to the controls (12.8 vs 2.9 ng/mL). The area under the ROC curve was 0.79 (95%
      CI, 0.710-0.83). The concentration of circulating DNA proved to be an important
      risk factor for the presence of the illness and a prognostic index in the follow
      up. CONCLUSIONS: The use of quantitative Real-Time PCR revealed that higher
      values of circulating DNA can be found in patients with lung neoplasm compared to
      the healthy controls. This could have practical implications such as the use in
      screening programs and a possible prognostic significance in the follow-up.

PMID- 18804891
TI  - Changing partners: moving from non-homologous to homologous centromere pairing in
      meiosis.
AB  - Reports of centromere pairing in early meiotic cells have appeared sporadically
      over the past thirty years. Recent experiments demonstrate that early centromere
      pairing occurs between non-homologous centromeres. As meiosis proceeds,
      centromeres change partners, becoming arranged in homologous pairs.
      Investigations of these later centromere pairs indicate that paired homologous
      centromeres are actively associated rather than positioned passively, side-by
      side. Meiotic centromere pairing has been observed in organisms as diverse as
      mice, wheat and yeast, indicating that non-homologous centromere pairing in early
      meiosis and active homologous centromere pairing in later meiosis might be themes
      in meiotic chromosome behavior. Moreover, such pairing could have previously
      unrecognized roles in mediating chromosome organization or architecture that
      impact meiotic segregation fidelity.

PMID- 18804893
TI  - Excision repair cross-complementation group 1 (ERCC1) in platinum-based treatment
      of non-small cell lung cancer with special emphasis on carboplatin: a review of
      current literature.
AB  - BACKGROUND: Patients diagnosed with advanced non-small cell lung cancer have a
      dismal prognosis and are often relative resistant to chemotherapy. A need for
      markers has emerged based on tumour biology in order to predict which patients
      will respond to treatment. Excision repair cross-complementation group 1 (ERCC1)
      has shown potential as a predictive marker in patients with NSCLC treated with
      cisplatin-based chemotherapy. Carboplatin has gained widespread use in the
      treatment of advanced NSCLC and its mechanisms of action are likely similar to
      that of cisplatin. MATERIALS AND METHODS: A literature review on ERCC1 was
      conducted as predictor in NSCLC patients receiving platinum-based treatment with
      emphasis on carboplatin. English language publications from January 1996 to
      February 2008 were eligible and data on methodology and outcome were recorded.
      RESULTS: Eight preclinical articles, 25 clinical articles and 1 clinical abstract
      were identified. Laboratory methods were mainly RT-PCR (reverse transcriptase
      polymerase chain reaction) or immunohistochemistry (IHC) for expression of ERCC1.
      Preclinical studies pointed towards similar mechanisms of chemotherapy-resistance
      among platinum compounds. A statistically significant benefit in outcome was
      found among NSCLC patients, who received adjuvant treatment, and had low-ERCC1
      expression. Advanced NSCLC patients treated with cisplatin showed improved
      response rates (RR) but no difference in other endpoints. Studies on advanced
      NSCLC patients treated with carboplatin were sparse, heterogeneous and small thus
      reporting varying results. CONCLUSION: The literature on advanced NSCLC patients
      treated with carboplatin or cisplatin are dominated by small and heterogeneous
      patient populations and yielded different results. No firm conclusions can be
      drawn on carboplatin based on the current literature. Research on the development
      of a reliable methodology is warranted followed by validation in large,
      prospective, randomized trials as ERCC1 may possibly play an important role as
      tumour marker in tailored chemotherapy for NSCLC.

PMID- 18804894
TI  - A phase III randomised study comparing concomitant radiochemotherapy as induction
      versus consolidation treatment in patients with locally advanced unresectable non
      small cell lung cancer.
AB  - As concomitant chemoradiotherapy for stage III NSCLC is associated with survival
      advantage in comparison to a sequential approach, we conducted a phase III
      randomised study aiming to determine the best sequence and safety of chemotherapy
      (CT) and chemoradiotherapy (CT-RT), using a regimen with cisplatin (CDDP),
      gemcitabine (GEM) and vinorelbine (VNR). Unresectable stage III NSCLC patients
      received CDDP (60 mg/m(2)), GEM (1g/m(2), days 1 and 8) and VNR (25mg/m(2), days
      1 and 8) with reduced dosage of GEM and VNR during radiotherapy (66Gy). Two
      cycles of CT with radiotherapy followed by two further cycles of CT alone were
      administered in arm A or the reverse sequence in arm B. The study was prematurely
      closed for poor accrual due to administrative problems. Forty-nine eligible
      patients were randomised. Response rates and median survival times were,
      respectively 57% (95% CI: 36-78%) and 17 months (95% CI: 9.3-24.6 months) in arm
      A and 79% (95% CI: 64-94%) and 23.9 months (95% CI: 13.3-34.5 months) in arm B
      (p>0.05). Chemotherapy dose-intensity was significantly reduced in arm A. Grade 3
      4 oesophagitis occurred in 5 patients. One case of grade 5 radiation pneumonitis
      was observed. In conclusion, chemoradiotherapy with CDDP, GEM and VNR appears
      feasible as initial treatment or after induction chemotherapy. Consolidation
      chemoradiotherapy seems less toxic with a better observed response rates and
      survival although no valid conclusion can be drawn from the comparison of both
      arms.

PMID- 18804895
TI  - Melanonychia, melanocytic hyperplasia, and nail melanoma in a Hispanic
      population.
AB  - OBJECTIVE: Longitudinal melanonychia (LM) is a common dermatologic problem
      encountered in everyday practice. Its diagnostic approach is critical as it can
      be an early sign of nail melanoma. Racial melanonychia is the entity most
      frequently associated with LM. Because there are no clinical data regarding these
      associations in a Mexican population, we conducted a prospective study. METHODS:
      A total of 68 consecutive patients given the clinical diagnosis of LM were
      included and a nail biopsy was performed to determine its cause. RESULTS: Racial
      melanonychia was found in 48 cases (68%), 4 cases (5.7%) were associated with
      benign melanocytic hyperplasia, and 4 cases (5.7%) had a nail apparatus
      malignancy. LIMITATIONS: Dermatoscopy and immunohistochemical stains were not
      used. Incisional transverse nail matrix biopsies were performed when melanonychia
      affected the middle portion of the nail plate. CONCLUSION: LM is most commonly
      associated with racial melanonychia in the Mexican population, but in nearly 6%
      of cases it may be linked with nail apparatus malignancy. To our knowledge, this
      is the first time a study of this nature was performed in a mestizo Hispanic
      population.

PMID- 18804896
TI  - Tips on how to write a paper.
AB  - Academics involve the search, education, and communication of knowledge. The
      credibility, advancement, and prestige of any specialty, program, or person
      involved in academics is enhanced by the quality of papers published. This occurs
      in the form of peer-reviewed research, along with observations and wisdom from
      institutional and private practice. Learning and mentoring medical manuscript
      writing skills is a process that improves with training and doing. The purpose of
      this manuscript is to serve as a guide with tips to aide the process of better
      writing, which may be particularly helpful to those in search of writing skills
      mentorship.

PMID- 18804897
TI  - Clinical correlates of vancomycin-resistant enterococci/meticillin-resistant
      Staphylococcus aureus co-colonization and co-infection in Singapore.

PMID- 18804898
TI  - Differential crosstalk between P2X7 and arachidonic acid in activation of mitogen
      activated protein kinases.
AB  - Accumulating evidence indicates that astroglial syncytium plays key role in
      normal and pathological brain functions. Astrocytes both in vitro and in situ
      respond to extracellular adenine-based nucleotides via the activation of P2
      receptors. Massive release of ATP from neurons and glial cells occurs as a result
      of pathological conditions of the brain leading to neuroinflammation and
      involving P2X7 receptors. In this study, we investigated whether P2X7 stimulation
      on cultured cortical astrocytes promoted a differential activation of mitogen
      activated protein kinases (MAPKs), and whether the second messenger arachidonic
      acid (AA), which is also a key modulator of neuroinflammation, affected the P2X7
      mediated MAPK phosphorylation. The results show that the synthetic P2X7 receptor
      agonist 2',3'-O-(4-benzoyl)benzoyl-ATP (BzATP), induced a concentration-dependent
      phosphorylation of MAPK ERK1/2, JNK and p38. Stimulation of ERK1/2, JNK and p38
      phosphorylation was also obtained by pathophysiological levels of extracellularly
      applied AA. Interestingly, a robust potentiation of ERK1/2 phosphorylation was
      elicited by co-application of BzATP and AA, whereas no differences were observed
      in JNK or p38 phosphosignals. The kinases activation showed a differential
      dependence on the presence of extracellular Ca(2+). The potentiation of BzATP
      mediated ERK1/2 phosphorylation was also observed in human embryonic kidney cells
      (HEK293) stably transfected with rat P2X7, but not in HEK cells expressing
      truncated P2X7 receptor lacking the full cytoplasmic carboxy-terminal or in those
      carrying the structurally related rat P2X2. AA and BzATP synergism in ERK1/2
      activation was abolished by cyclo-oxygenase and lipoxygenase pathway inhibitors.
      The result that ERK1/2-mediated transduction pathway is synergistically modulated
      by ATP and AA signalling depicts possible novel pharmacological targets for
      interfering with pathological activation of astroglial cells.

PMID- 18804899
TI  - [An unusual origin of peripheral facial nerve palsy].

PMID- 18804900
TI  - Clinical relevance of parenteral nutrition prescription and administration in 200
      hospitalized patients: a quality control study.
AB  - BACKGROUND & AIMS: Optimal implementation of parenteral nutrition (PN) is
      required to promote clinical outcome and costs control. This prospective quality
      control study examined if PN prescription was justified and PN administration was
      adequate to cover the nutritional needs of patients hospitalized in the Geneva
      University Hospital. METHODS: Two-hundred consecutive patients receiving PN were
      included from Medicine, Intensive Care or Surgery Units. PN prescription was
      considered justified if oral feeding or enteral nutrition were contraindicated or
      provided less than 40% of the energy target after 5 days. PN was considered
      adequate if it covered 90%-110% of the recommended need for energy (i.e., 110% of
      the Harris-Benedict formula) and proteins (i.e., 1.2 or 1.0 g protein/kg body
      weight/day for patients < or = or >65 years, respectively), and was supplemented
      with vitamins and trace elements. RESULTS: PN prescription was justified in all
      but 14 patients (7%). However, PN administration was frequently inadequate:
      overfeeding (62%) was more often observed than underfeeding (14%), particularly
      among thin, elderly and female patients (P<0.01). Moreover, PN was not
      supplemented with vitamins and/or trace elements in 47 patients (24%).
      CONCLUSION: PN prescription is generally justified but PN administration is often
      inadequate. Further teaching of medical teams and quality control surveys are
      warranted to optimize PN practices.

PMID- 18804901
TI  - Perforated, custom-shaped, porous, polyethylene-coated titanium mesh implants in
      the treatment of large defects of the orbital wall.

PMID- 18804902
TI  - A story of scrutiny and fear: Australian midwives' experiences of an external
      review of obstetric services, being involved with litigation and the impact on
      clinical practice.
AB  - OBJECTIVES: to describe Australian midwives' experiences of an external review of
      obstetric services, involvement in legal proceedings and the impact on midwives'
      clinical practice and personal wellbeing. BACKGROUND: the external review process
      (commonly referred to as the 'Douglas Inquiry') was initiated by a state
      government and was in response to hospital staff and consumer complaints that
      focused on anomalies in client care and a significantly high rate of adverse
      outcomes and clinical errors. It took place within the context of a number of
      legal proceedings against medical practitioners. As a result, some midwives
      employed by the hospital were called to give evidence at a variety of legal
      forums. DESIGN: a qualitative study using an explorative descriptive design.
      Snowball sampling was used to invite 16 Australian midwives to participate in a
      tape-recorded interview. Thematic analysis and the techniques associated with
      constant comparison were used to analyse the data. SETTING: Australian maternity
      tertiary referral centre. FINDINGS: the analysis identified two overarching
      themes, 'A story of scrutiny' and 'A story of fear', each with a number of
      subthemes. 'A story of scrutiny' consists of three subthemes. 'A cloak and dagger
      affair' reflects the midwives' sense of being and feeling 'exposed' and
      'vulnerable' whilst simultaneously being 'kept in the dark' and uninformed during
      the review process. The subtheme 'Being thrown to the wolves' describes the
      midwives' experiences of being involved, as witnesses, in medico-legal
      proceedings. The third subtheme, 'The Inquiry followed them home' outlines the
      effect on midwives' emotional wellbeing and personal relationships. The second
      major theme, 'A story of fear' again consists of a number of subthemes. 'Feeling
      unsafe at work: a culture of fear' describes the midwives' experiences of working
      within an environment they perceive as driven by the fear of litigation. In order
      to protect themselves and maintain a sense of control, the midwives adopted a
      number of strategies to 'feel safe' including defensive decision making and
      moving towards a medical philosophy of care. These concepts are captured within
      the subtheme 'Covering your back: setting boundaries'. The impact on
      relationships between midwives, women and medical practitioners is described
      within the subtheme 'Professional relationship: coloured by fear'. The effect on
      midwives' confidence and the resultant negative emotions elicited make up the
      subtheme 'Between a rock and a hard place: the midwives' distressing dilemma'.
      Finally the subtheme, 'Opting out: the changing nature of professional work
      practices' describes the specific professional decisions and work strategies that
      midwives made about their ability to continue working in an environment that they
      perceived as threatening. CONCLUSION: the findings suggest that the midwife
      participants in this small study were totally unprepared and ill equipped, both
      personally and professionally, to deal with the consequences of working within an
      environment that was the centre of a number of high profile legal proceedings and
      an extensive external review of obstetric services. The midwives were naive about
      legal processes and unprepared for the legal 'game playing' and media attention
      that often accompanies court proceedings. Despite the fact that no midwife faced
      litigation, the participants described their work environment as becoming
      increasingly stressful and permeated by a culture of fear. In turn, this
      situation has reinforced the need for some midwives to adopt an 'institution'
      ideology which reinforces birth as an abnormal event that needs to be medically
      managed. This has led to changes in professional and personal work practices. The
      findings also have implications for the midwifery workforce and retention.
      Although the findings are context specific, this study provides valuable insight
      into the phenomena of fear of litigation and its impact on midwifery practice.
      Given the similarities concerning obstetric litigation in some other Western
      nations, the findings have relevance in the international midwifery arena.

PMID- 18804903
TI  - Vitamin K deficiency bleeding (VKDB) in early infancy.
AB  - Vitamin K deficiency bleeding (VKDB) is a rare and potentially life-threatening
      bleeding disorder of early infancy. Vitamin K stores are low at birth; thereafter
      breast-fed infants are at risk because of low concentrations in human milk.
      Classical VKDB occurs in the first week of life, is related to delayed or
      inadequate feeding and is readily prevented by small doses of vitamin K at birth.
      Late VKDB peaks at 3-8 weeks, typically presents with intracranial haemorrhage
      often due to undiagnosed cholestasis with resultant malabsorption of vitamin K.
      Diagnosis can be difficult but PIVKA-II measurements can provide confirmation
      even several days post-treatment. Without vitamin K prophylaxis, the incidence of
      late VKDB in Europe is 4-7 cases per 10(5) births; it is higher in SE Asia where
      in rural, low-income areas some 0.1% of affected infants may suffer intracranial
      bleeding. Late VKDB is largely preventable with parenteral vitamin K providing
      the best protection. The efficacy of oral prophylaxis is related to the dose and
      frequency of administration. Most multi-dose oral regimens provide protection for
      all except a small reservoir of infants with undetected hepatobiliary disease.
      Targeted surveillance of high-risk groups (e.g. biliary atresia) offers a novel
      approach to assess efficacy of prophylaxis.

PMID- 18804904
TI  - Exposure assessment of French women and their newborn to brominated flame
      retardants: determination of tri- to deca- polybromodiphenylethers (PBDE) in
      maternal adipose tissue, serum, breast milk and cord serum.
AB  - In the frame of a French monitoring program, tri- to deca-
      polybromodiphenylethers (PBDE) have been measured in maternal and cord serum,
      adipose tissue, and breast milk samples, collected from 93 volunteer women during
      caesarean deliveries. The seven major tri- to heptaBDE (BDE-28, 47, 99, 100, 153,
      154, and 183) were detected in adipose tissue and breast milk with cumulated
      median values of 2.59 and 2.51 ng g(-1) l w. Nine highly brominated octa- to
      decaBDE (BDE-196, 197, 201, 202, 203, 206, 207, 208 and 209) was performed in the
      same samples, with cumulated median values of 2.73 and 3.39 ng g(-1) l w in
      adipose tissue and breast milk, respectively. At this opposite, median levels of
      octa- to decaBDE in maternal and cord serum appeared significantly higher than
      the levels of tri- to heptaBDE in the same matrices, i.e. 8.85 and 12.34 versus
      0.98 and 0.69 ng g(-1) l w, respectively.

PMID- 18804905
TI  - Information, power and environmental justice in Botany: the role of community
      information systems.
AB  - In the environmental conflict that surrounds the sighting of hazardous waste
      facilities there is usually a volatile mix of disparities in power, expertise and
      information access as well as differing views on risk, which are all played out
      amidst commercial arrangements and environmental justice concerns. In recent
      times, the volatility of this mix has been further compounded by the growing
      climate of public concern and distrust surrounding scientific developments and
      technology. While there is no 'quick fix' to the complex conflict that this
      entails, community information systems (CISs) based on participatory models can
      help address the outstanding issues of capacity, information access, power
      inequities and environmental justice. CISs are an effective response to the five
      crucial elements of a toxic dispute, that is, the dialogue, capacity building,
      information access, evaluation of hazards and risk, and expertise. This paper
      will review the role of community accessible information systems in the dispute
      in Botany over the management and destruction of Orica Australia's stockpile of
      the persistent organic pollutant, hexachlorobenzene (HCB). It will focus on the
      role of CIS in responding to the challenges for expert information delivery, and
      in addressing the disparity of informational power within the toxic dispute.

PMID- 18804906
TI  - Rebuttal from authors re: Vincenzo Ficarra, Antonio Galfano and Stefano
      Cavalleri. Is simple enucleation a minimal partial nephrectomy responding to the
      EAU guidelines' recommendations? Eur Urol 2009;55:1315-8.

PMID- 18804907
TI  - Treatment with sunitinib enabled complete resection of massive lymphadenopathy
      not previously amenable to excision in a patient with renal cell carcinoma.
AB  - We present a case of previously unresectable lymphadenopathy in a patient with
      renal cell carcinoma treated with sunitinib. Complete resection of a 15-cm left
      renal cell carcinoma was initially impossible due to massive retroperitoneal
      disease and encasement of the great vessels and mesenteric vessels. Residual
      retroperitoneal disease from a radical nephrectomy was treated with the oral,
      multitargeted receptor tyrosine kinase inhibitor, sunitinib. Tumour shrinkage
      following five cycles of treatment allowed uncomplicated complete resection of
      the lymphadenopathy. Follow-up after 6 mo showed no evidence of disease
      recurrence.

PMID- 18804908
TI  - Glucosamine is an effective chemo-sensitizer via transglutaminase 2 inhibition.
AB  - Aberrant increases of transglutaminase 2 (TGase 2) in tumors contribute to drug
      resistance. The role of TGase 2 in cancer pathogenesis was unknown until we
      showed that TGase 2 activates NF-kappaB in the absence of kinase-dependent
      phosphorylation. It appears that increased expression of TGase 2 is responsible
      for the constitutive activation of NF-kappaB in cancer cells. We have
      demonstrated that TGase 2 inhibition using siRNA, cystamine or R2 peptide
      promotes cell death in drug-resistant cancer cells through NF-kappaB
      inactivation. Therefore, a safe and effective small molecule for TGase 2
      inhibition is being sought in the development of therapeutics for malignant
      cancers. By screening for TGase inhibitors in a natural compound library, we
      found that glucosamine has a TGase 2 inhibitory effect in vitro. Glucosamine also
      recovered the depletion of I-kappaBalpha via TGase 2 inhibition, which resulted
      in a decrease of NF-kappaB activity in EcR293/TG cells. Furthermore, glucosamine
      efficiently promoted cell death via inhibiting TGase 2-mediated NF-kappaB
      activation in drug-resistant breast cancer cells. These results suggest that
      glucosamine, as a TGase 2 inhibitor, might be an attractive novel target for
      treatment of malignant cancers.

PMID- 18804909
TI  - Transformation of carbon tetrachloride by biogenic iron species in the presence
      of Geobacter sulfurreducens and electron shuttles.
AB  - The transformation of carbon tetrachloride (CT) by biogenic iron species produced
      from the bioreduction of various Fe(III) oxides in the presence of Geobacter
      sulfurreducens and electron shuttles were investigated. Cysteine and
      anthraquinone-2,6-disulfonate (AQDS) at concentrations of 0.5mM and 10microM,
      respectively, were added as the electron shuttles. Addition of electron shuttles
      enhanced the extent of reduction and rate of ferric oxide reduction. The
      bioreduction extents of ferric oxides by G. sulfurreducens in the presence of
      electron shuttles were 22.8-48.3% for ferrihydrite, 6.5-17.2% for hematite, and
      3.0-11.3% for goethite. After normalization to the surface areas, a higher rate
      of CT reduction was observed per unit of adsorbed Fe(II) on crystalline oxides.
      The produced biogenic Fe(II) from crystalline iron oxides was 2.8-7.6 times lower
      than that obtained from ferrihydrite, while the surface area-normalized rate
      constant for iron-mediated CT transformation in the presence of goethite and
      hematite were, by factors of 2-21, higher than that obtained using ferrihydrite.
      These results clearly depict that G. sulfurreducens drove the reduction of CT
      primarily through the formation of biogenic iron species in the presence of
      electron shuttle under iron-reducing conditions and that it is a surface area
      dependent process.

PMID- 18804910
TI  - Large pore bi-functionalised mesoporous silica for metal ion pollution treatment.
AB  - Here we demonstrate aminopropyl and mercatopropyl functionalised and bi
      functionalised large pore mesoporous silica spheres to extract various metal ions
      from aqueous solutions towards providing active sorbents for mitigation of metal
      ion pollution. Elemental analysis (EA) and FTIR techniques were used to quantify
      the attachment of the aminopropyl and mercatopropyl functional groups to the
      mesoporous silica pore wall. Functionalisation was achieved by post-synthesis
      reflux procedures. For all functionalised silicas the functionalisation refluxing
      does not alter particle morphology/agglomeration of the particles. It was found
      that sorptive capacities of the mesoporous silica towards the functional groups
      were unaffected by co-functionalisation. Powder X-ray diffraction (PXRD) and
      nitrogen adsorption techniques were used to establish the pore diameters, packing
      of the pores and specific surface areas of the modified mesoporous silica
      spheres. Atomic absorption (AA) spectroscopy and inductively coupled plasma
      atomic emission spectrometry (ICP-AES) techniques were used to measure the
      extraction efficiencies of each metal ion species from solution at varying pHs.
      Maximum sorptive capacities (as metal ions) were determined to be 384micromolg(
      1) for Cr, 340micromol g(-1) for Ni, 358micromol g(-1) for Fe, 364micromol g(-1)
      for Mn and 188micromol g(-1) for Pd.

PMID- 18804911
TI  - Utilization of lignite power generation residues for the production of
      lightweight aggregates.
AB  - A novel process is proposed for the utilization of lignite combustion solid
      residues in the production of inflammable lightweight aggregates (LWA). The
      process consists of two stages, pelletization and sintering, and carbon contained
      in BA was used as the process fuel. The main residues bottom ash (BA) and fly ash
      (FA) from Megalopolis power plant were characterized, mixed in different
      proportions and treated through pelletization and sintering process. Sintering
      benefits from combustion of BA carbon content and the product is a hardened
      porous cake. The energy required for achievement of high temperatures, in the
      range of 1250 degrees C, was offered by carbon combustion and CO(2) evolution is
      responsible for porous structure formation. Selected physical properties of
      sintered material relevant to use as lightweight aggregates were determined,
      including bulk density, porosity and water absorption. Bulk density varies from
      0.83 to 0.91 g/cm(3), porosity varies from 60% to 64% and water absorption varies
      from 66% to 80%. LWA formed is used for the production of lightweight aggregate
      concrete (LWAC). Thermal conductivity coefficient varies from 0.25 to 0.37 W/mK
      (lower than maximum limit 0.43 W/mK) and compressive strength varies from 19 to
      23 MPa (higher than minimum limit 17 MPa). The results indicate that sintering of
      lignite combustion residues is an efficient method of utilization of carbon
      containing BA and production of LWA for structural and insulating purposes.
      Carbon content of BA is a key factor in LWA production. Finally, this research
      work comprises the first proposed application for utilization of BA in Greece.

PMID- 18804912
TI  - Elemental and spectroscopic characterization of humic-acid-like compounds during
      composting of olive mill by-products.
AB  - Humic acids (HAs) were isolated at different stages of composting from two piles
      of solid olive mill residues (SOR) treated for the first 30 days with tap water
      (pile C1) or olive mill wastewater (pile C2), for a total composting period of 9
      months. The HA fractions were characterized by elemental analysis, UV-visible,
      Fourier transform infrared and fluorescence spectroscopy in order to monitor
      humification process and the maturity of the composts. As composting proceeded,
      the elemental composition of the humic acids showed a decrease in C and H
      content, and in the C/N ratio, and an increase in N and O contents and in the C/H
      and O/C ratios. These changes could be attributed to a loss of aliphatic groups
      and to an increase of aromatic character, polycondensation and degree of
      oxidation of the HAs. Spectroscopic data agree and support these results,
      suggesting that the chemical and structural features of the HAs of both composts
      tend to reach those typical of native soil HAs, that is compounds with a high
      degree of humification and a high molecular weight and complexity. Therefore,
      both composting processes seem suitable to produce well-humified organic matter,
      with important benefits for their use in soil amendment. No differences appeared
      between the two treatments concerning the humic character of the two final
      composts.

PMID- 18804913
TI  - Degradation of malachite green in aqueous solution by Fenton process.
AB  - In this study, advanced oxidation process utilizing Fenton's reagent was
      investigated for degradation of malachite green (MG). The effects of different
      reaction parameters such as the initial MG concentration, initial pH, the initial
      hydrogen peroxide concentration, the initial ferrous concentration and the
      reaction temperature on the oxidative degradation of MG have been investigated.
      The optimal reacting conditions were experimentally found to be pH 3.40, initial
      hydrogen peroxide concentration=0.50mM and initial ferrous concentration=0.10mM
      for initial MG concentration of 20mg/L at 30 degrees C. Under optimal conditions,
      99.25% degradation efficiency of dye in aqueous solution was achieved after 60
      min of reaction.

PMID- 18804914
TI  - Optimizing operating parameters of a honeycomb zeolite rotor concentrator for
      processing TFT-LCD volatile organic compounds with competitive adsorption
      characteristics.
AB  - In this study, we attempted to enhance the removal efficiency of a honeycomb
      zeolite rotor concentrator (HZRC), operated at optimal parameters, for processing
      TFT-LCD volatile organic compounds (VOCs) with competitive adsorption
      characteristics. The results indicated that when the HZRC processed a VOCs stream
      of mixed compounds, compounds with a high boiling point take precedence in the
      adsorption process. In addition, existing compounds with a low boiling point
      adsorbed onto the HZRC were also displaced by the high-boiling-point compounds.
      In order to achieve optimal operating parameters for high VOCs removal
      efficiency, results suggested controlling the inlet velocity to <1.5m/s, reducing
      the concentration ratio to 8 times, increasing the desorption temperature to 200
      225 degrees C, and setting the rotation speed to 6.5rpm.

PMID- 18804915
TI  - A longitudinal study of the efficacy of a comprehensive pain rehabilitation
      program with opioid withdrawal: comparison of treatment outcomes based on opioid
      use status at admission.
AB  - Use of opioids for chronic non-cancer pain is controversial and the efficacy of
      comprehensive pain rehabilitation programs (CPRPs) that incorporate opioid
      withdrawal requires further investigation. We test the hypothesis that patients
      with chronic pain and longstanding opioid use who undergo opioid withdrawal in
      the course of rehabilitative treatment will experience significant and sustained
      improvement in pain and functioning similar to patients who were not taking
      opioids. A longitudinal design study compared 373 consecutive patients admitted
      to the Mayo Clinic Pain Rehabilitation Center at admission, discharge and six
      month posttreatment by opioid status at admission. Measures of pain severity,
      depression, psychosocial functioning, health status, and pain catastrophizing
      were used to assess between- and within-group differences. Treatment involved a 3
      week interdisciplinary pain rehabilitation program focused on functional
      restoration. Over one-half of patients (57.1%) were taking opioids daily at
      admission. The majority of patients (91%) completed rehabilitation and 70% of
      patients who completed the program returned questionnaires six months
      posttreatment. On admission, patients taking low- and high-dose opioids reported
      significantly greater pain severity (P=.001) and depression (P=.001) than the non
      opioid group. Significant improvement was found on all outcome variables
      following treatment (P<.001) and six-month posttreatment (P<.001) regardless of
      opioid status at admission. There were no differences between the opioid and non
      opioid groups upon discharge from the program or at six months following
      treatment. CONCLUSION: Patients with longstanding CPRP on chronic opioid therapy,
      who choose to participate in interdisciplinary rehabilitation that incorporates
      opioid withdrawal, can experience significant and sustained improvement in pain
      severity and functioning.

PMID- 18804916
TI  - The dynamic mechanisms of placebo induced analgesia: Evidence of sustained and
      transient regional involvement.
AB  - Previously, we demonstrated that placebo analgesia (PA) accompanies reductions in
      neural activity during painful stimulation. This study investigated areas of the
      brain where the neural activity was increased during PA. The literature has
      associated PA with two potential mechanisms of action; one sustained (e.g.,
      engaged for the duration of PA), the other, transitory (e.g., a feedback
      mechanism). We propose that PA results from the engagement of two complementary
      pain-modulation mechanisms that are identified with fMRI data as a main effect
      for condition or a time *condition interaction. The mechanism with sustained
      activity should activate the emotional regulation circuitry needed for memory
      formation of the event. The mechanism with transient activity should process
      cognitive and evaluative information of the stimuli in the context of the placebo
      suggestion to confirm the expectations set by it. To identify regions involved
      with these mechanisms, we re-analyzed fMRI data from two conditions: baseline (B)
      and PA. Results support the presence of both mechanisms, identified as two neural
      networks with different temporal characteristics. Regions with sustained activity
      primarily involved the temporal and parahippocampal cortices. Conversely, brain
      regions with transient activity included linguistic centers in the left
      hemisphere and frontal regions of the right hemisphere generally associated with
      executive functioning. Together, these mechanisms likely engage analgesic
      processes and then simply monitor the system for unexpected stimuli, effectively
      liberating resources for other processes. Identifying brain regions associated
      with pain-modulation with different temporal profiles is consistent with the
      multidimensionality of PA and highlights the need for continued investigation of
      this construct.

PMID- 18804917
TI  - Reverse flow flap use in upper extremity burn contractures.
AB  - Upper extremity contractures still happen and constitute one of the most trying
      challenges in burn patients. This series comprised of 4 radial forearm flaps, 14
      dorsoulnar artery flaps, and 4 medial arm flaps, all of which were used in a
      reverse pattern for upper extremity postburn contractures. The reverse flow
      radial forearm flap (RRFF) was chosen for reconstruction of extensive palmar
      contractures after burn. The reverse flow dorsoulnar flap (RDUF) was used
      particularly for reconstruction of the hypothenar aspect of the hand which
      requires moderate size tissue transfer. The reverse medial arm flap (RMAF) was
      used for elbow contractures after burn. In the first RMAF, venous congestion
      occurred and was finaly resolved with minimal flap loss, which was managed with
      STSG later. In the following 3 cases the flap was supercharged with anastomosis
      of the brachial vein into the antebrachial vein. Both RRFF and RDUF may provide a
      smooth and efficient solution. However, RMAF has a significant venous problem,
      which may result in flap loss, therefore, this flap should not be considered as a
      first option in the elbow area.

PMID- 18804918
TI  - Nicotine dependence, psychological distress and personality traits as possible
      predictors of smoking cessation. Results of a double-blind study with nicotine
      patch.
AB  - AIM: Nicotine replacement therapy (NRT) is an effective treatment for smokers who
      want to quit, however, the rates of successful quitting can be improved even
      more. In this context, nicotine dependence (assessed via the Fagerstrom Tolerance
      Questionnaire, FTQ), psychological distress (measured via the Symptom Rating
      Test, SRT), and personality traits (evaluated via the Adult Eysenck Personality
      Inventory, AEPI) were evaluated as possible predictors of smoking cessation.
      RESULTS: A total of 297 cigarette smokers were followed for one year as part of a
      NRT double-blind, parallel group, randomized trial. Baseline nicotine dependence
      (weeks 12 and 26: p<0.05), AEPI neuroticism (weeks 12 and 52: p<0.05), and AEPI
      psychoticism (weeks 12 and 52: p<0.05) scores significantly influenced the
      outcome of smoking cessation during one-year of follow-up. An increase in
      psychological distress during follow-up was associated with a lower probability
      of quitting smoking (p=0.000). CONCLUSIONS: Nicotine dependence, neuroticism,
      psychoticism and, over time, psychological distress were the main factors
      influencing the long-term outcome (i.e., up to 12 months) of smoking cessation
      under NRT.

PMID- 18804919
TI  - Nonbreast second malignancies after treatment of primary breast cancer.
AB  - PURPOSE: To determine the incidence and risk factors for nonbreast second
      malignancies (NBSMs) in women after treatment for primary breast cancer. METHODS
      AND MATERIALS: Between January 1985 and December 1995, a total of 1,084 breast
      cancer patients were analyzed for NBSMs. Detailed analysis was carried out for
      age, family history, disease stage, radiation therapy, chemotherapy, hormone
      therapy, other clinical/pathologic characteristics, and site of NBSMs. The Cox
      proportional hazard regression model was used to estimate the relative risk of
      NBSMs. RESULTS: Median follow-up was 12 years. In total, 33 cases of NBSMs were
      noted in 29 patients. The overall incidence of NBSM was 3%, and the median time
      for NBSMs was 7 years. The most common NBSMs were gynecologic (22 patients),
      gastrointestinal (4 patients), head and neck (3 patients), hematologic (2
      patients), lung (1 patient), and thyroid (1 patient). The NBSMs rate at 12 years
      was 2.4% for both mastectomy and radiation therapy groups. In the subset of
      patients less than 45 years of age at the time of treatment, the NBSMs rate was
      0.7% as compared with 4.6% in patients more than 45 years of age (p = 0.001).
      Statistically significant higher incidences of endometrial and ovarian cancer
      were seen in patients with hormonal therapy (5.2%) as compared with patients
      without hormonal therapy (1.8%, p = 0.002). Women with a family history of breast
      cancer had a higher incidence (6%) of endometrial and ovarian malignancy compared
      with women without such a history (2.1%, p = 0.003). Chemotherapy did not affect
      the risk of second malignancy. CONCLUSION: The most common NBSMs in this study
      were gynecologic. Family history of breast cancer was a high risk factor for
      NBSMs. No risk of NBSMs with radiotherapy was observed.

PMID- 18804920
TI  - Examining the characteristics of unstaged colon and rectal cancer cases.
AB  - BACKGROUND: There are only three published studies that have examined unstaged
      cancers, including breast, prostate and colorectal cancer, but none have
      specifically examined which aspects of tumor staging were missing. The objective
      of the study was to identify which stage components were missing, to characterize
      and to identify predictors of unstaged cancer, and to evaluate prognosis of
      unstaged in colon and rectal cancer patients. METHODS: Data on all colon and
      rectal cancer cases diagnosed during 1991 to 2002 were identified from the
      Surveillance, Epidemiology and End Results (SEER) database. Information included
      in the analysis encompassed socio-demographics; tumor size (T); number of lymph
      nodes (N); metastases (M); SEER summary stage; SEER sites; cancer treatment;
      month and year of diagnosis; and last date known alive. RESULTS: The study
      included 128,418 colon and 44,616 rectal cancer patients. Overall, 5.1% of colon
      and 7.8% of rectal cancer patients were unstaged. Compared to staged cases, both
      unstaged colon and rectal cancer cases were more likely to be older, African
      American, female, diagnosed in the Northeast and South, and have unknown
      treatment (all p<0.001). The stage component of M was found to be the factor
      missing most frequently which attributed most to being unstaged. Survival was
      significantly higher in unstaged and the overall cohort compared to distant
      staged colon and rectal cancer patients (both p<0.001) except for patients > or
      =65 years old (p>0.99). CONCLUSIONS: Given that unstaged cases differ from
      staged, the findings have methodological implications in accounting for unstaged
      cases in epidemiological and health services research.

PMID- 18804921
TI  - [Robot-assisted surgery and female infertility].

PMID- 18804922
TI  - [Response to the article by C. Le Ray and F. Audibert: "duration of pushing in
      labor: literature review"].

PMID- 18804923
TI  - Cost analysis of clinic and office-based treatment of opioid dependence: results
      with methadone and buprenorphine in clinically stable patients.
AB  - The cost of providing and receiving treatment for opioid dependence can determine
      its adoption. To compare the cost of clinic-based methadone (MC, n=23), office
      based methadone (MO, n=21), and office-based buprenorphine (BO, n=34) we
      performed an analysis of treatment and patient costs over 6 months of maintenance
      in patients who had previously been stabilized for at least 1 year. We performed
      statistical comparisons using ANOVA and chi-square tests and performed a
      sensitivity analysis varying cost estimates and intensity of clinical contact.
      The cost of providing 1 month of treatment per patient was $147 (MC), $220 (MO)
      and $336 (BO) (p<0.001). Mean monthly medication cost was $93 (MC), $86 (MO) and
      $257 (BO) (p<0.001). The cost to patients was $92 (MC), $63 (MO) and $38 (BO)
      (p=0.102). Sensitivity analyses, varying cost estimates and clinical contact,
      result in total monthly costs of $117 to $183 (MC), $149 to $279 (MO), $292 to
      $499 (BO). Monthly patient costs were $84 to $133 (MC), $55 to $105 (MO) and $34
      to $65 (BO). We conclude that providing clinic-based methadone is least
      expensive. The price of buprenorphine accounts for a major portion of the
      difference in costs. For patients, office-based treatment may be less expensive.

PMID- 18804924
TI  - Beyond quitting: predictors of teen smoking cessation, reduction and acceleration
      following a school-based intervention.
AB  - There remains a great need for effective, cost-efficient, and acceptable youth
      smoking cessation interventions. Unfortunately, only a few interventions have
      been demonstrated to increase quit rates among youth smokers, and little is known
      about how elements of cessation interventions and participants' psychosocial
      characteristics and smoking histories interact to influence program outcomes.
      Additionally, few studies have examined how these variables lead to complete
      smoking abstinence, reduction or acceleration over the course of a structured
      cessation intervention. Data for the present investigation were drawn from a
      sample of teen smokers (n=5892) who voluntarily participated in either a
      controlled study or field study (i.e., no control group) of the American Lung
      Association's Not On Tobacco (N-O-T) program between 1998 and 2006 in five
      states. Results suggest that those who reduce smoking (but do not achieve full
      abstinence) are similar to those who quit on most measures except stage of
      change. Furthermore, it was found that those who increased smoking were heavier
      smokers at baseline, more addicted, were more likely to have parents, siblings,
      and significant others who smoked and reported less confidence in and less
      motivation for quitting than did those who quit or reduced smoking. Finally, a
      path model demonstrated how peers, siblings and romantic partners affected
      tobacco use and cessation outcomes differently for males and females.
      Implications for interventions are discussed.

PMID- 18804925
TI  - Discordance of prenatal and neonatal brain development in twins.
AB  - BACKGROUND: Discordance of birth weight has been observed in twin pairs, though
      little is known about prenatal and early neonatal discordance of head and brain
      size, and the role that zygosity and chorionicity play in discordances of early
      brain development in twins. AIMS: To compare prenatal and neonatal discordances
      of head size in monozygotic-monochorionic (MZ-MC), monozygotic-dichorionic (MZ
      DC), and same-sex dizygotic-dichorionic twin pairs (DZ). STUDY DESIGN: Subjects
      prospectively had ultrasounds at 22 and 32 weeks gestational age, and magnetic
      resonance imaging (MRI) of the brain MRI after birth. SUBJECTS: 88 twin pairs
      recruited from two university hospital prenatal diagnostic clinics; 22 MZ-MC, 17
      MZ-DC, and 49 same-sex DZ pairs. OUTCOME MEASURES: Discordance of head
      circumference (HC) and weight at 22 weeks, 32 weeks and birth, as well as
      intracranial volume (ICV) on neonatal MRI. RESULTS: There were no group
      differences in discordance of head circumference and weight on the 22 or 32 week
      ultrasounds, or at birth. MZ-MC twins tended to have numerically greater
      discordances of HC and weight. There was a significant group difference in ICV on
      neonatal MRI (ANOVA, p=0.0143), with DZ twins having significantly greater
      discordance than MZ-MC (p=0.028) or MZ-DC (p=0.0131) twins. CONCLUSIONS: This
      study indicates that zygosity and chorionicity do not contribute to significant
      discordances of head size in late prenatal development. DZ twins do have
      significantly greater discordances of ICV on neonatal MRI, suggesting a
      relatively greater genetic influence on brain growth in the first weeks after
      birth.

PMID- 18804926
TI  - CPAP and the preterm infant: lessons from the COIN trial and other studies.
AB  - Bronchopulmonary dysplasia is associated with ventilation. Nasal continuous
      positive airway pressure (nCPAP) allows earlier weaning in ventilated infants.
      Starting nCPAP from shortly after birth to prevent ventilation has been
      questioned because it prevents an early use of surfactant. The efficacy of early
      surfactant was assessed in infants electively intubated, few having received
      antenatal steroids. Recent trials using nCPAP from birth in 25 to 28 week infants
      describe more customised strategies: in the COIN trial, 27-28 week infants
      breathing at birth benefit the most from nCPAP. Fewer infants received oxygen on
      day 28; they had fewer days of ventilation and no increase in morbidities despite
      having more pneumothoraces. The REVE trial suggests that intubation with early
      surfactant administration followed by nCPAP mostly benefits to 25-26 week
      infants. Thus, nCPAP is feasible from birth. The overall strategy should take
      into account infants' gestational age, maturation and behaviour in the delivery
      room.

PMID- 18804927
TI  - Influence of IGF-I on buffalo (Bubalus bubalis) spermatozoa motility, membrane
      integrity, lipid peroxidation and fructose uptake in vitro.
AB  - The objective of the present experiment was to examine the influence of mean
      physiological concentration of insulin-like growth factor-I (IGF-I) on frozen
      thawed Surti buffalo (Bubalus bubalis) spermatozoa functional parameters, i.e.,
      motility, plasmalemma integrity, acrosomal integrity, functional membrane
      integrity, lipid peroxidation and fructose uptake in vitro. Frozen-thawed semen
      samples (n=6) were washed in tris buffer and divided into two equal parts
      (control and IGF-I groups). Only in the IGF-I group, IGF-I (rhIGF-I analogue) was
      added to a final concentration of 100 ng/ml. The samples were incubated at 37
      degrees C for 2h and the assessments were made at 0, 30, 60, 90 and 120 min of
      incubation. The mean concentration of the buffalo seminal plasma (n=17) IGF-I was
      116.83+/-28.34 ng/ml (range 41.4-198.95). IGF-I had significant effect on the
      total motility (P<0.01), progressive forward motility (P<0.01), functional
      membrane integrity (P<0.05) and lipid peroxidation levels (P<0.05) during the 120
      min study period as assessed by area under curve. Treatment with IGF-I increased
      (P<0.01) the total spermatozoa motility at 30, 60 and 90 min as compared to the
      control. The progressive forward motility was significantly (P<0.01) higher at 60
      and 90 min of incubation. The addition of IGF-I resulted in significant (P<0.01)
      increase in straight-line velocity (VSL, microm/s) as compared to the control at
      60 and 90 min of incubation. The linearity (%) was significantly (P<0.01) higher
      in IGF-I treated semen as compared to control at 60 min of incubation.
      Plasmalemma integrity in IGF-I group was significantly (P<0.05) higher than
      control at 30 and 60 min of incubation. The functional membrane integrity
      differed significantly (P<0.01) between groups (control and IGF-I) at 60 and 90
      min of incubation. The percentage of acrosomal intact spermatozoa decreased
      continuously over a period of time in both the groups. As compared to 0 min of
      incubation, the significant (P<0.05) loss of acrosome was observed at 60 and 90
      min of incubation in control (63.87+/-3.17 vs. 58.52+/-2.54) and IGF-I (61.60+/
      2.26 vs. 56.11+/-2.12) groups, respectively. Lipid peroxidation levels were
      significantly lower in IGF-I group at 90 min (P<0.05) and 120 min (P<0.01) of
      incubation than the control group. Fructose utilization was significantly higher
      in IGF-I group as compared to control at 30 min (P<0.05) and 60 min (P<0.01) of
      incubation. The present study suggests that addition of IGF-I improve spermatozoa
      functional parameters by reducing lipid peroxidation levels.

PMID- 18804928
TI  - Abnormal fast activity in infancy with paroxysmal downwards gaze.
AB  - We report here on 8 infants who showed paroxysmal downwards gaze (PDG). The time
      of initial appearance of PDG ranged from one month to five months (mean: 2.7
      months) of corrected age. Seven out of eight patients showed interictal spikes in
      EEG, so they were started on prophylactic therapy with antiepileptic drugs. In
      five of the eight patients, PDG ceased, either spontaneously or with
      antiepileptic drug treatment, by four to eight months of corrected age. Six out
      of eight patients showed localized spikes and peculiar abnormal fast activity
      (AFA) in the occipital area and five of these patients later developed West
      syndrome. These AFA were observed on EEGs recorded at the time of initial PDG
      appearance, before hypsarrhythmia was observed and before tonic spasms appeared.
      We were able to exclude the possibility that PDG was a subtle epileptic seizure
      by confirming the temporal discordance between individual episodes of PDG and AFA
      with video-EEG monitoring. Yet topographic data showed that AFA in these patients
      was characteristically located in the occipital area, with a distribution similar
      to that of the fast activity which accompanied the tonic spasms that later
      developed in these patients. As a risk factor for developing WS, we propose the
      clinical symptom of PDG with characteristic occipital AFA visible in the EEG,
      both of which represent damage to the occipital region including the optic
      radiation.

PMID- 18804929
TI  - A novel POMT2 mutation causes mild congenital muscular dystrophy with normal
      brain MRI.
AB  - We report a patient harboring a novel homozygous mutation of c.604T>G (p.F202V)
      in POMT2. He showed delayed psychomotor development but acquired the ability to
      walk at the age of 3 years and 10 months. His brain MRI was normal. No ocular
      abnormalities were seen. Biopsied skeletal muscle revealed markedly decreased but
      still detectable glycosylated forms of alpha-dystroglycan (alpha-DG). Our results
      indicate that mutations in POMT2 can cause a wide spectrum of clinical phenotypes
      as observed in other genes associated with alpha-dystroglycanopathy. Presence of
      small amounts of partly glycosylated alpha-DG may have a role in reducing the
      clinical symptoms of alpha-dystroglycanopathy.

PMID- 18804930
TI  - A catalog of SCN1A variants.
AB  - Over the past 10 years mutations in voltage-gated sodium channels (Na(v)s) have
      become closely associated with inheritable forms of epilepsy. One isoform in
      particular, Na(v)1.1 (gene symbol SCN1A), appears to be a superculprit,
      registering with more than 330 mutations to date. The associated phenotypes range
      from benign febrile seizures to extremely serious conditions, such as Dravet's
      syndrome (SMEI). Despite the wealth of information, mutational analyses are
      cumbersome, owing to inconsistencies among the Na(v)1.1 sequences to which
      different research groups refer. Splicing variability is the core problem:
      Na(v)1.1 co-exists in three isoforms, two of them lack 11 or 28 amino acids
      compared to full-length Na(v).1.1. This review establishes a standardized
      nomenclature for Na(v)1.1 variants so as to provide a platform from which future
      mutation analyses can be started without need for up-front data normalization. An
      online resource--SCN1A infobase--is introduced.

PMID- 18804931
TI  - [Acute hepatitis after cutaneous application of an artisanal topical ointment
      with mercury].
AB  - There is a risk of severe neurological disease, nephropathy and cutaneous
      complications during mercury poisoning. We report a case of acute generalized
      exanthematous pustulosis, associated with histologically confirmed acute
      cytolytic hepatitis without liver failure, after application of a topical home
      made ointment containing mercury. The patient was previously sensitized with
      mercurothiolate. A high level of mercury was found in the blood (68 microg/L,
      normal < 5 microg/L). Clinical and biological features disappeared after the
      ointment was discontinued. Biological acute hepatitis was probably from type IV
      sensitization, like that seen in acute generalized exanthematous pustulosis, with
      no evidence of direct mercury poisoning and after lithiasis, viral, immune and
      drug side effects were excluded. Liver injury during acute generalized
      exanthematous pustulosis is uncommon and usually mild, but should be searched
      for.

PMID- 18804932
TI  - Mature and immature ovarian teratomas: CT, US and MR imaging characteristics.
AB  - Ovarian teratomas (OTs) are the most common germ cell neoplasm. They include
      mature cystic teratomas, monodermal teratomas (neural tumors, struma ovarii,
      carcinoid tumors) and immature teratomas. Teratomas are the most common benign
      ovarian neoplasms in women less than 45 years old. OTs are usually characterized
      by ultrasound (US) and magnetic resonance (MR) whereas they are usually an
      incidental finding on CT. The purpose of this paper is to review the most common
      types of teratomas and to describe CT, US and MR imaging features of the various
      types of mature and immature OTs.

PMID- 18804933
TI  - CT features of adenomyosis.
AB  - OBJECTIVES: To determine the computed tomography (CT) features of adenomyosis in
      patients with known adenomyosis as established with magnetic resonance (MR)
      imaging. METHODS: A computerized search identified 16 women with pelvic MR
      diagnosis of adenomyosis who also had enhanced pelvic CT. Original CT reports
      were reviewed for potential prospective diagnosis of adenomyosis. CT images were
      reviewed for enhancement phase, inner and outer myometrium attenuation, uterine
      enlargement (width >6 cm), inner myometrial thickening (> or =12 mm), and
      myometrial cysts. RESULTS: Adenomyosis was detectable on CT in 8 of 16 patients.
      For these 8 patients, inner and outer myometrium distinction was excellent in 7
      (88%) and limited in 1 (12%), and mean inner myometrial thickness was 25 mm
      (range 14-47 mm). CT enhancement phase was parenchymal in 7 (88%), uterus was
      enlarged in 8 (100%), and 7 (88%) had myometrial cysts. Adenomyosis was focal in
      5 (63%), diffuse in 2 (25%), and both in 1 (12%). None of the original CT reports
      included adenomyosis as a diagnosis. CONCLUSIONS: CT can suggest a diagnosis of
      adenomyosis based on uterine enlargement, thickened inner myometrium, and/or
      myometrial cysts.

PMID- 18804934
TI  - LC-UV-PDA and LC-MS studies to characterize degradation products of glimepiride.
AB  - Degradation products of glimepiride formed under different forced conditions have
      been characterized through LC-UV-PDA and LC-MS studies. Glimepiride was subjected
      to forced decomposition under the conditions of hydrolysis, oxidation, dry heat
      and photolysis, in accordance with the ICH guideline Q1A(R2). The reaction
      solutions were chromatographed on reversed phase C8 (150 mm x 4.6mm i.d., 5
      microm) analytical column. In total, five degradation products (I-V) were formed
      under various conditions. The drug degraded to products II and V under acid and
      neutral hydrolytic conditions while products I, III and IV were formed under the
      alkaline conditions. The products II and V were also observed on exposure of drug
      to peroxide. No additional degradation product was shown up under photolytic
      conditions. All the products, except I, could be characterized through LC-PDA
      analyses and study of MS fragmentation pattern in both +ESI and -ESI modes.
      Product I could not be identified, as it did not ionize under MS conditions. The
      products II, III and V matched, respectively, to impurity B (glimepiride
      sulfonamide), impurity J and impurity C (glimepiride urethane) listed in European
      Pharmacopoeia. The product IV was a new degradation product, characterized as [[4
      [2-(N-carbamoyl)aminoethyl]phenyl]sulfonyl]-3-trans-(4-methylcyclohexyl) urea.
      The degradation pathway of the drug to products II-V is proposed, which is yet
      unreported.

PMID- 18804935
TI  - Frequency and follow-up of incidental findings on trauma computed tomography
      scans: experience at a level one trauma center.
AB  - OBJECTIVES: Incidental findings found on computed tomography (CT) scan during the
      Emergency Department evaluation of trauma patients are often benign, but their
      presence must always be communicated to patients, who should be referred for
      follow-up care. Our objective was to quantify the frequency of these incidental
      CT findings in trauma patients. A secondary goal was to determine how often these
      lesions were communicated to patients and how often patients were referred for
      follow-up. METHODS: We performed a retrospective chart review of 500 consecutive
      patients presenting as trauma activations. Subjects received head, chest, or
      abdomen/pelvis CT scans at our hospital. Patients were identified using our
      trauma registry. Final CT reports were examined and discharge summaries were
      reviewed for basic demographics. Scans with incidental findings prompted detailed
      secondary review of discharge summaries to determine follow-up. Investigators
      reviewed incidental findings and classified them into three groups by clinical
      importance, using predetermined criteria. RESULTS: Of the 500 patient charts
      identified for review, 480 (96%) were available, yielding 1930 CT reports for
      analysis. Incidental findings were noted in 211 of 480 (43%) patients and on 285
      (15%) of the 1930 CT studies performed for the 480 patients. Of available patient
      records, only 27% of patient charts had mention of the finding in the discharge
      summary, had documentation of an in-hospital workup, or had documentation of a
      referral for follow-up. Most-concerning lesions, such as suspected malignancies
      or aortic aneurysms, accounted for 15% of all incidental findings and were
      referred for follow-up in only 49% of cases. CONCLUSIONS: Incidental findings
      were noted in 15% of trauma CT scans. Follow-up was poor, even for potentially
      serious findings. Further studies should examine the long-term outcome of
      patients with these findings.

PMID- 18804936
TI  - Obesity-related knowledge and beliefs in obese adults attending a specialist
      weight-management service: implications for weight loss over 1 year.
AB  - OBJECTIVE: Cognitive approaches to obesity management assume that weight loss is
      more likely to occur if individuals perceive many benefits and few costs.
      Research to-date has been limited by the lack of prospective studies. METHODS: A
      longitudinal study design. At baseline, obese patients attending weight
      management clinics (n=104) completed a questionnaire that assessed knowledge and
      beliefs regarding obesity's health and social/aesthetic consequences (Obesity
      Risk Knowledge (ORK-10) scale and the Obesity Beliefs scale), self-reported
      weight/height, goal weight, health-related quality of life, and sociodemographic
      characteristics. Medical records were also reviewed. At the 12-month follow-up, a
      second questionnaire assessed self-reported weight/height. RESULTS: At baseline,
      average ORK-10 scale scores were 4/10. At follow-up, 32 out of the 66
      participants retained on the study did not gain weight (48.5%). For these
      participants, weight loss was associated with endorsement of the health
      (r(s)=0.40) and the social/aesthetic (r(s)=0.31) costs of obesity (p<0.05).
      CONCLUSION: Despite their high-risk status, participants demonstrated low levels
      of knowledge regarding obesity's health risks. Weight loss was associated with
      greater awareness of the health and social/aesthetic costs of obesity. PRACTICE
      IMPLICATIONS: This study suggests that health education is required to facilitate
      informed choices and supports the use of cognitive approaches which promote both
      the health and social/aesthetic consequences of obesity.

PMID- 18804937
TI  - Immediate endovascular repair for acute traumatic injuries of the thoracic aorta:
      a multicenter analysis of 28 cases.
AB  - OBJECTIVE: Endovascular repair of injured thoracic aorta offers a new minimal
      invasive therapeutic option that could be beneficial in the urgent management of
      polytrauma patients. The aim of this study was to assess our multicenter
      experience of immediate endovascular repair for acute traumatic injuries of the
      thoracic aorta. METHODS: Between April 2002 and October 2007, all patients
      treated for an acute traumatic injury of the thoracic aorta, in a less than 12
      hour delay, by endovascular repair, were reviewed retrospectively in three
      Parisian trauma centers. Collected data included age, sex, associated
      comorbidities, and traumatic lesions to determine the Traumatic Injury Severity
      Score (TRISS), the type of aortic lesion assessed by computed tomography (CT)
      scan and transesophageal ultrasonography, technical aspects of endovascular
      repair, length of hospital stay, and postoperative mortality. Patients were
      regularly followed by clinical examination, chest radiographs, and thoracic CT
      scan. RESULTS: Twenty-eight patients (20 males, mean age 45 +/- 18.8 years) were
      treated in a median delay of 5 hours (range 2 to 10 hours) after initial trauma.
      They all experienced severe traumatic injuries with a mean predictive mortality
      of 55.6% +/- 33.1% according to TRISS. Aortic lesions were associated with aortic
      parietal hematoma (71%), hemomediastinum (86%), and hemothorax (68%). All
      endovascular procedures were technically successful through femoral (n = 24) or
      iliac access (n = 4), in a mean operating time of 94 +/- 35.8 minutes. Proximal
      sealing of the endografts required the coverage of the origin of the left
      subclavian artery in 13 cases and of the left common carotid in one case. The
      median of hospital stay was 27 days (range 9 to 127 days), with an overall
      hospital mortality of 17.9% (n = 5). All deaths were unrelated to the aortic
      rupture or the stent placement, and no intervention-related morbidity or
      mortality was recorded during a median follow-up of 24 months (range 5 to 73
      months). CONCLUSION: Endovascular stent grafting allows an immediate efficient
      repair for acute traumatic injuries of the thoracic aorta. This early management
      is, however, associated with a high in-hospital mortality, related to the severe
      concomitant injuries of such unselected multitrauma patients.

PMID- 18804939
TI  - Repair of complex renal artery aneurysms by laparoscopic nephrectomy with ex vivo
      repair and autotransplantation.
AB  - OBJECTIVE: Renal artery aneurysms are being discovered more frequently due to
      increased use of non-invasive imaging. Complex renal artery aneurysms involving
      multiple secondary or tertiary branches are not amenable to in vivo or
      endovascular treatment and often require ex vivo repair with autotransplantation.
      In order to minimize incisional morbidity and hasten recovery, we developed a
      technique of laparoscopic nephrectomy combined with backbench ex vivo repair,
      followed by autotransplantation through a small laparoscopic extraction incision.
      This study describes our initial experience with this combined technique in
      patients that were not candidates for endovascular techniques or in vivo arterial
      reconstruction. METHODS: Seven patients with complex renal artery aneurysms
      underwent laparoscopic nephrectomy and ex vivo repair with multiple saphenous
      vein grafts and autotransplantation through the small laparoscopic extraction
      incision. The aneurysms ranged from 2.5 to 5.0 cm. In all cases, the aneurysm was
      resected ex vivo, leaving multiple branch arteries that were extended with
      saphenous vein grafts. Arterial inflow was then re-established with sequential
      saphenous vein anastomoses to the external iliac artery. Ureteral reconstruction
      was performed via standard Lich ureteroneocystostomy. Patients were followed
      postoperatively for two to eight years. RESULTS: Laparoscopic nephrectomy with ex
      vivo repair of complex aneurysms was successfully employed in seven patients with
      renal aneurysms that were not amenable to endovascular or in vivo repair. There
      were no incisional morbidities and all patients had significant improvements in
      symptoms post-operatively. Renal function remained unchanged and there were no
      ureteral complications following surgery. All patients had postoperative
      ultrasound imaging done at two years which demonstrated patency of the
      anastomoses. The mean hospital stay was four days (range, two to seven days).
      CONCLUSION: Repair of complex renal artery aneurysms involving distal branch
      arteries remains a challenge. This new technique combines the advantages of
      minimally invasive surgery with the effectiveness of ex vivo aneurysm repair.

PMID- 18804940
TI  - Staging the neoaortoiliac system: feasibility and short-term outcomes.
AB  - BACKGROUND: The neoaortoiliac system (NAIS) has gained popularity as a durable
      procedure for treating aortic graft infections. However, one of the disadvantages
      has been a long operation that can take up to 10 hours. The goal of this study
      was to assess the feasibility of staging the NAIS procedure with deep vein
      harvest a day before the aortofemoral bypass and evaluate if staging had any
      effect on graft patency or morbidity and mortality, or both. METHODS: We reviewed
      data for all the NAIS procedures performed for aortic graft infections at a
      tertiary care university hospital. The femoral popliteal veins of patients
      undergoing the staged NAIS were harvested a day in advance and left in situ. The
      next day patients underwent the prosthetic graft excision with reconstruction
      using the femoral popliteal veins. Patients with aortic occlusion on presentation
      were not candidates for vein harvest in advance and underwent a unilateral bypass
      with a subsequent femorofemoral bypass as a second stage. RESULTS: In the last 8
      years, 26 patients (17 men, 9 women; mean age, 62.6 +/- 8.3 years) underwent the
      NAIS procedure for aortic graft infections. Mean follow-up was 15.7 months.
      Primary assisted graft patency was 100%. There were 11 patients in the staged
      group and 10 patients in the nonstaged group. All the staged patients underwent
      vein mobilization a day before excision of aortic prosthesis. Despite undergoing
      a separate procedure for vein harvesting at a different time, there was no
      difference in total operative time (12.0 +/- 1.8 vs 11.9 +/- 2.2 hours),
      operative blood loss (2.6 +/- 1.2 vs 3.4 +/- 2.4 L), and requirements for
      transfusion for blood products (6.7 +/- 3.7 vs 6.0 +/- 5.4 U) or crystalloid
      (11.3 +/- 3.1 vs 10.9 +/- 2.4 L) between the staged group and nonstaged groups.
      One amputation occurred in each group. The perioperative mortality was 18% for
      the staged group and 20% for nonstaged group. The 12-month survival was 72% for
      staged and 70% for nonstaged NAIS. No graft-related complications were observed
      from the preoperative vein harvest. CONCLUSION: The NAIS can be staged without
      compromising the efficacy of the procedure as evident by excellent long-term
      patency and control of the infection. By reducing the duration of the primary
      procedure, staging may be beneficial to both the patient and the surgeon.

PMID- 18804941
TI  - The quantitative benefit of isolated, segmental, pharmacomechanical thrombolysis
      (ISPMT) for iliofemoral venous thrombosis.
AB  - BACKGROUND: Early thrombus removal in patients with iliofemoral deep venous
      thrombosis (IFDVT) reduces postthrombotic morbidity. Preserving valve function
      and relieving venous obstruction prevents deterioration of quality of life and
      loss of economic potential. The preferred method for treating IFDVT is catheter
      directed thrombolysis (CDT). Recently, isolated segmental pharmacomechanical
      thrombolysis (ISPMT) has emerged as a treatment option for patients with
      extensive IFDVT. The purpose of our study is to determine whether there are
      advantages to using ISPMT as the primary treatment for patients with iliofemoral
      IFDVT and, if so, to quantify those advantages relative to CDT. METHODS: Forty
      three patients with IFDVT were treated with percutaneous CDT between May 2003 and
      June 2007. Twenty-one patients (27 limbs) were treated with CDT and 22 patients
      (25 limbs) were treated with ISPMT +/- CDT. Demographics, extent of thrombus,
      procedural details, and thrombus resolution were recorded. RESULTS: Treatment
      time (55.4 vs 23.4 hours; P < .0001) and dose of rt-PA (59.3 vs 33.4 mg; P =
      .0009) were decreased and overall lytic success (60% vs 80%; P = .0016) increased
      with ISPMT. Adjunctive venoplasty and stenting, complications, hospital length-of
      stay (LOS), and intensive care unit LOS were similar between groups. CONCLUSION:
      ISPMT offers more effective thrombus removal in less time and with a reduced dose
      of thrombolytic agent. However, decreased treatment time did not translate into
      decreased hospital or ICU stay. Longer-term follow-up is required to determine
      whether improved thrombus resolution translates to better functional outcome and
      reduced postthrombotic morbidity.

PMID- 18804942
TI  - Current imaging modalities to visualize vulnerability within the atherosclerotic
      carotid plaque.
AB  - BACKGROUND: There is increasing evidence that plaque vulnerability, rather than
      the degree of stenosis, is important in predicting the occurrence of subsequent
      cerebral ischemic events in patients with carotid artery stenosis. The many
      imaging modalities currently available have different properties with regard to
      the visualization of the extent of vulnerability in carotid plaque formation.
      METHODS: Original published studies were identified using the MEDLINE database
      (January 1966 to March 2008). Manual cross-referencing was also performed.
      RESULTS: There is no single imaging modality that can produce definitive
      information about the state of vulnerability of an atherosclerotic plaque. Each
      has its own specific drawbacks, which may be the use of ionizing radiation or
      nephrotoxic contrast agents, an invasive character, low patient tolerability, or
      simply the paucity of information obtained on plaque vulnerability. Functional
      molecular imaging techniques such as positron emission tomography (PET), single
      photon emission-computed tomography (SPECT) and near infra-red spectroscopy
      (NIRS) do seem able accurately to visualize and even quantify features of plaque
      vulnerability and its pathophysiologic processes. Promising new techniques like
      near infra-red fluorescence imaging are being developed and may be beneficial in
      this field. CONCLUSION: There is a promising role for functional molecular
      imaging modalities like PET, SPECT, or NIRS related to improvement of selection
      criteria for carotid intervention, especially when combined with CT or MRI to add
      further anatomical details to molecular information. Further information will be
      needed to define whether and where this functional molecular imaging will fit
      into a clinical strategy.

PMID- 18804943
TI  - The management of severe aortoiliac occlusive disease: endovascular therapy
      rivals open reconstruction.
AB  - OBJECTIVE: Aortobifemoral bypass (ABF) grafting has been the traditional
      treatment for extensive aortoiliac occlusive disease (AIOD). This retrospective
      study compared the outcomes and durability of recanalization, percutaneous
      transluminal angioplasty, and stenting (R/PTAS) vs ABF for severe AIOD. METHODS:
      Between 1998 and 2004, 86 patients (161 limbs) underwent ABF (n = 75) or
      iliofemoral bypass (n = 11), and 83 patients (127 limbs) underwent R/PTAS. All
      patients had severe symptomatic AIOD (claudication, 53%; rest pain, 28%; tissue
      loss, 12%; acute limb ischemia, 7%). The analyses excluded patients treated for
      aneurysms, extra-anatomic procedures, and endovascular treatment of iliac
      stenoses. Original angiographic imaging, medical records, and noninvasive testing
      were reviewed. Kaplan-Meier estimates for patency and survival were calculated
      and univariate analyses performed. Mortality was verified by the Social Security
      database. RESULTS: The ABF patients were younger than the R/PTAS patients (60 vs
      65 years; P = .003) and had higher rates of hyperlipidemia (P = .009) and smoking
      (P < .001). All other clinical variables, including cardiac status, diabetes,
      symptoms at presentation, TransAtlantic Inter-Society Consensus stratification,
      and presence of poor outflow were similar between the two groups. Patients
      underwent ABF with general anesthesia (96%), often with concomitant treatment of
      femoral or infrainguinal disease (61% endarterectomy, profundaplasty, or distal
      bypass). Technical success was universal, with marked improvement in ankle
      brachial indices (0.48 to 0.84, P < .001). Patients underwent R/PTAS with local
      anesthesia/sedation (78%), with a 96% technical success rate and similar
      hemodynamic improvement (0.36 to 0.82, P < .001). At the time of R/PTAS, 21% of
      patients underwent femoral endarterectomy/profundaplasty or bypass (n = 5) for
      concomitant infrainguinal disease. Limb-based primary patency at 3 years was
      significantly higher for ABF than for R/PTAS (93% vs 74%, P = .002). Secondary
      patency rates (97% vs 95%), limb salvage (98% vs. 98%), and long-term survival
      (80% vs 80%) were similar. Diabetes mellitus and the requirement of distal bypass
      were associated with decreased patency (P < .001). Critical limb ischemia at
      presentation (tissue loss, hazard ratio [HR], 8.1; P < .001), poor outflow (HR,
      2; P = .023), and renal failure (HR, 2.5; P = .02) were associated with decreased
      survival. CONCLUSION: R/PTAS is a suitable, less invasive alternative to ABF for
      the treatment of severe AIOD. Repair of the concomitant femoral occlusive disease
      is often needed regardless of open or endovascular treatment. Infrainguinal
      disease negatively affects the durability of the procedure and patient survival.

PMID- 18804944
TI  - Reversal effect of resveratrol on multidrug resistance in KBv200 cell line.
AB  - A multidrug-resistant clone of human oral epidermoid carcinoma KB cells was
      isolated by stepwise selection on exposure to increasing doses of vincristine.
      The final clone, KBv200, obtained after ethylmethane sulfonate mutagenesis showed
      156-fold higher resistance to vincristine than KB cells. The cells were also
      cross-resistant to paclitaxel and adriamycin. The aim of this study was to
      explore the reversal effect and potential mechanism of resveratrol on KBv200
      cells. MTT assay was used to investigate the reversal index of resveratrol to
      vincristine, adriamycin and paclitaxel. Cell apoptosis was measured by flow
      cytometry. RT-PCR and western blot were used to detect mRNA and protein
      expression of multidrug-resistant gene MDR1 and apoptosis-suppressing gene Bcl-2.
      Resveratrol produced a synergistic effect combined with the chemotherapeutic
      agents and reversed the multidrug-resistant phenotype of KBv200 cells. Flow
      cytometry confirmed that the percentage of apoptotic cell increased when KBv200
      cells were exposed to resveratrol. The results of gene detection showed that the
      expression levels of MDR1 and Bcl-2 were decreased upon resveratrol treatment.
      Resveratrol can efficiently reverse multidrug resistance in KBv200 cells. The
      potential mechanism may be via inhibiting the multidrug-resistant gene
      expressions and/or promoting cell apoptosis.

PMID- 18804945
TI  - Optimizing the success of a palliative care consult service: how to average over
      110 consults per month.
AB  - The widespread need for palliative care has prompted the development of hospital
      based palliative care consult services to provide a more interdisciplinary
      approach to managing advanced illness and end-of-life concerns. Establishing a
      successful consult service is a challenging task. This is a descriptive study of
      the development of a palliative care consult service (PCCS) within a non-profit,
      multi-hospital health system, and the five successful strategies used to optimize
      growth over the first five years. The PCCS is a mobile interdisciplinary team
      established to provide accessible, comprehensive end-of-life care and symptom
      management to patients with advanced illness within the health care system.
      Critical to its success, the team developed and maintained a database to document
      growth and ensure continuous quality improvement. A description of this database
      is provided, along with current performance outcomes. The program has prospered
      since its inception in 2002, with a 47% average annual growth over the first five
      years. The PCCS now averages 110 consults per month and has treated more than
      3500 patients. This growth can be directly attributed to the five key strategies
      that have been used to plan, develop, and expand the program.

PMID- 18804946
TI  - Symptom prevalence and longitudinal follow-up in cancer outpatients receiving
      chemotherapy.
AB  - Palliative care for cancer patients receiving chemotherapy in the outpatient
      setting is important. The aims of this study were 1) to identify symptom
      prevalence and intensity in cancer patients receiving chemotherapy and 2) to
      describe longitudinal follow-up data obtained from repeated assessment using the
      distress thermometer (DT). Questionnaires were distributed to consecutive cancer
      outpatients newly starting chemotherapy at the first appointment and at every
      hospital visit. The questionnaire included the severity of 11 symptoms (M. D.
      Anderson Symptom Inventory [MDASI], Japanese version), the DT, and the need for
      help in four psychosocial areas (decision-making, economic problems, nutrition,
      and daily activities). In total, 4000 questionnaires were returned by 462
      patients. The frequently identified problems were oral problems (21%), insomnia
      (19%), psychological distress (defined as a DT score of 6 or more; 15%), help
      with information and decision-making (14%), severe fatigue (8.2%), and severe
      appetite loss (6.3%). Cluster analysis identified four symptom clusters: 1)
      fatigue and somnolence; 2) pain, dyspnea, and numbness; 3) nausea, appetite loss,
      and constipation; and 4) psychological distress. Of 165 patients with a DT of
      score 6 or more, 115 patients (70%) demonstrated a DT score below 6 at a median
      of 17 days follow-up. In the remaining 50 patients who had a DT score of 6 or
      more at follow-up, 34 patients (68%) had one or more physical symptoms rated at 7
      or more on an 11-point numeric rating scale. Compared with patients with a DT
      score below 6 at follow-up, patients with a DT score of 6 or more at follow-up
      had higher levels of all physical symptoms. Frequent symptoms experienced by
      cancer outpatients receiving chemotherapy may be categorized as: 1) psychosocial
      issues (insomnia, psychological distress, decision-making support); 2) nutrition
      gastrointestinal issues (oral problems, appetite loss, nausea); 3) fatigue; and
      4) pain, dyspnea, and numbness. Developing a systematic intervention program
      targeting these four areas is urgently required. The DT score may be highly
      influenced by coexisting physical symptoms, and future studies to develop an
      appropriate system to identify patients with psychiatric comorbidity are
      necessary.

PMID- 18804947
TI  - An examination of recent non-clinical panic attacks, panic disorder, anxiety
      sensitivity, and emotion regulation difficulties in the prediction of generalized
      anxiety disorder in an analogue sample.
AB  - Both non-clinical panic attacks and panic disorder (PD) have been found to be
      associated with generalized anxiety disorder (GAD). This study examined a proxy
      risk factor model of the relationship between non-clinical panic attacks, PD, and
      GAD. Specifically, it was proposed that non-clinical panic attacks and PD predict
      GAD only due to their shared association with anxiety sensitivity (AS) and
      difficulties in emotion regulation. Results demonstrated that emotion regulation
      difficulties reliably predicted GAD above and beyond the experience of non
      clinical panic attacks and PD. However, although PD lost strength as a predictor,
      it remained significantly associated with GAD in the full model, providing only
      partial support for the proposed proxy risk factor model. Findings speak to the
      underlying role of emotion regulation difficulties in GAD, and suggest that it
      may be the shared relationship of these difficulties with both PD and GAD that
      partially explain the association of these disorders.

PMID- 18804948
TI  - Compression of the common femoral artery by a lymphangioma causing intermittent
      claudication.
AB  - External compression of the common femoral artery secondary to a lymphangioma has
      not been reported before. A female patient presented with intermittent
      claudication of the right lower extremity. She was examined with Doppler vascular
      ultrasound and computed tomography, which demonstrated a cystic mass that did not
      infiltrate the arterial wall. At operation we found a mass adjacent to and
      causing compression of the common femoral artery, which was completely resected.
      The histological report described a cystic cavernomatous lymphangioma. Surgical
      treatment of lymphangiomas includes complete resection of the lesion and arterial
      reconstruction or bypass if necessary. In our case, the lymphangioma did not
      infiltrate the arterial wall and was completely resected.

PMID- 18804949
TI  - Impact of the introduction of endovascular aneurysm repair in high-risk patients
      on our practice of elective treatment of infrarenal abdominal aortic aneurysms.
AB  - The aim of this work was to evaluate, in terms of activity and immediate
      postoperative results, the modifications of our elective surgical treatment of
      infrarenal abdominal aortic aneurysms (AAAs) resulting from the use of stent
      grafts to treat AAAs, following the recommendations issued by the French Health
      Products Safety Agency (AFSSAPS) in December 2003. This monocentric and
      retrospective study used the clinical data of patients operated on for
      asymptomatic AAA between January 2001 and December 2006. Endovascular treatment
      of AAAs with aortic stent grafts was introduced in our current practice in
      January 2004, following the recommendations of the AFSSAPS (high-risk patients
      for open surgery presenting with an AAA > or =50 mm). Group I was composed of
      patients operated on between January 2001 and December 2003 according to the
      standard open technique. Group II was composed of patients operated on between
      January 2004 and December 2006 with either standard open surgery or endovascular
      surgery. The main criteria of evaluation were the number of operated patients,
      their American Society of Anesthesiology (ASA) score of surgical risk, and the
      intrahospital morbidity and mortality. The number of treated patients
      significantly increased between these two periods (group I n = 49, group II n =
      88, with 38 endovascular treatments; p < 0.001), without any changes in average
      age (70 vs. 72 years), percentage of men (93.7% vs. 95.5%), and mean AAA size
      (57.8 vs. 56 mm) between the two groups. ASA scores were significantly higher in
      group II (ASA III and IV, group I = 20.4% vs. group II = 55.7%; p < 0.0001),
      whereas the intrahospital mortality rate (4.1% vs. 3.4%) and the rate of major
      postoperative complications (16.3% vs. 11%) have remained stable. In group II,
      the median duration of hospitalization was significantly reduced (12 vs. 9 days,
      p < 0.001). In conclusion, in our center, following the AFSSAPS recommendations,
      the introduction of endovascular treatment has enabled us to electively treat a
      greater number of AAA patients with higher surgical risk, without aggravating the
      immediate postoperative results.

PMID- 18804950
TI  - Concurrent splenic peliosis and vascular Ehlers-Danlos syndrome.
AB  - This case report describes concurrent splenic peliosis and vascular Ehlers-Danlos
      syndrome (EDS) in a 59-year-old male patient. After splenic rupture due to
      peliosis, the complicated postoperative period hinted at the possibility of
      vascular EDS. This diagnosis was confirmed by genetic testing, which revealed a
      novel point mutation in the COL3A1 gene, c.2545G-->C, leading to a codon encoding
      for arginine instead of glycine (p.Gly849Arg). In addition, a histological
      diagnosis of splenic peliosis could be established.

PMID- 18804951
TI  - Leiomyoma of the greater saphenous vein: a case report and review of the
      literature.
AB  - Greater saphenous vein tumors are exceedingly rare, whether benign or malignant.
      Leiomyoma is one of the benign vascular tumors that can present as a localized
      mass; however, the diagnosis cannot be made clinically. Multiple radiologic
      imagings are usually required, as well as histological examination, to make a
      definitive diagnosis. This tumor is treated by wide excision along with a normal
      portion of the vessel, and the recurrence rate is very low. We describe the case
      of a patient with great saphenous vein leiomyoma.

PMID- 18804952
TI  - Robotic-assisted laparoscopic dissection of the infrarenal aorta and iliac
      artery: a technical description and early results.
AB  - We report our initial experience with a novel robotic-assisted dissection of the
      infrarenal aorta and iliac arteries for the treatment of aortoiliac occlusive
      disease and abdominal aortoiliac aneurysm. Seven patients underwent the procedure
      using the da Vinci Surgical System. Transabdominal, retroperitonal dissection of
      the aorta and iliac arteries was completed using the robotic system; then, a mini
      laparotomy and hand-sewn aorta-to-graft anastomosis were performed. There was no
      mortality in this series of patients. This novel technique may overcome the
      difficulty of aortic dissection in a purely laparoscopic aortic surgery and
      serves as a bridging step toward totally robotic-assisted aortic surgery.

PMID- 18804953
TI  - Capturing human data in a letter counting task: accessibility and action
      centeredness in representing cognitive skills.
AB  - This work presents an integrated model of skill learning that takes into account
      both implicit and explicit processes and both action-centered and non-action
      centered knowledge. The existing distinction between procedural and declarative
      knowledge unnecessarily confounds these two aspects (action-centeredness and
      accessibility), and can be made clearer through separating the two aspects. The
      model is used to simulate human data in a letter counting task. The work shows
      how the data in this task may be captured using either action-centered knowledge
      alone or both action-centered and non-action-centered knowledge, though the
      combined approach produced a better fit. The results demonstrate the difference
      between these approaches and provide a new perspective on skill learning.

PMID- 18804954
TI  - Learning layered ranking functions with structured support vector machines.
AB  - The relationship between bipartite ranking algorithms, graph theory and ROC
      analysis has been formerly established with data sampled from two categories
      (i.e. classes). In this article, we discuss extensions for more general ranking
      models, with data sampled from, in general, r ordered categories. Similarly, such
      models can be visualized by means of a layered ranking graph in which each path
      in the graph corresponds to an r-tuple of correctly ranked objects with one
      object of each class. From an ROC analysis point of view, the fraction of
      correctly ranked r-tuples equals the volume under the ROC surface (VUS) for r
      ordered categories. Unlike the conventional kernel approach of minimizing the
      pairwise error, we try to optimize the fraction of correctly ranked r-tuples. A
      large number of constraints appear in the resulting quadratic program, but the
      optimal solution can be computed in O(n3) time for samples of size n with
      structured support vector machines and graph-based techniques. Our approach can
      offer benefits for applications in various domains. On various synthetic and
      benchmark data sets, it outperforms the pairwise approach for balanced as well as
      unbalanced problems. In addition, scaling experiments confirm the theoretically
      derived time complexity.

PMID- 18804955
TI  - Automatic detection of blue-white veil and related structures in dermoscopy
      images.
AB  - Dermoscopy is a non-invasive skin imaging technique, which permits visualization
      of features of pigmented melanocytic neoplasms that are not discernable by
      examination with the naked eye. One of the most important features for the
      diagnosis of melanoma in dermoscopy images is the blue-white veil (irregular,
      structureless areas of confluent blue pigmentation with an overlying white
      "ground-glass" film). In this article, we present a machine learning approach to
      the detection of blue-white veil and related structures in dermoscopy images. The
      method involves contextual pixel classification using a decision tree classifier.
      The percentage of blue-white areas detected in a lesion combined with a simple
      shape descriptor yielded a sensitivity of 69.35% and a specificity of 89.97% on a
      set of 545 dermoscopy images. The sensitivity rises to 78.20% for detection of
      blue veil in those cases where it is a primary feature for melanoma recognition.

PMID- 18804956
TI  - Paroxysmal fast activity: an interictal scalp EEG marker of epileptogenesis in
      children.
AB  - PURPOSE: High-frequency oscillations (>100Hz) have been proposed as localized
      markers of epileptic networks, but require intracranial electroencephalographic
      (EEG) recordings. This study explored if beta- and gamma-frequency paroxysmal
      fast activity (PFA), recorded interictally during non-REM sleep, could be used as
      a scalp EEG marker of epileptogenesis in children. METHODS: The presence and
      scalp location of PFA was visually identified in 681 patients with overnight
      video-EEG (age 0-18 years), and compared with ictal onset sites. The clinical
      features of patients with PFA were compared with patients without PFA along with
      evidence of PFA evolution in 35 patients who had multiple video-EEG records.
      RESULTS: PFA was present in 16% of all patients and in 28% of those with
      seizures. PFA was more frequently observed in EEGs from patients 3 years of age
      or younger (>40%), and children with infantile spasms (85%). When present, PFA
      predicted if the patient had epilepsy with 97% accuracy, and was not found in
      individuals with non-epileptic events. PFA localized with EEG-ictal onset sites
      with 91% sensitivity and 82% accuracy. Ictal scalp EEG events began with beta-
      and gamma-frequencies in 80% of patients with PFA, and they had increased seizure
      frequencies compared with non-PFA cases. In patients with multiple video-EEG
      studies, PFA showed progression over increased numbers of electrodes in 74%,
      improvement in 15%, and remained unchanged in 12% and correlated with seizure
      evolution. PFA was not associated with other seizure types, anatomic location,
      type of antiepileptic drug, etiology, or histopathology. CONCLUSIONS: While
      relatively infrequent, interictal PFA was specific in identifying younger
      children with epilepsy, co-localized with the ictal onset sites on scalp video
      EEG, and progressed and correlated with seizure severity. We propose that PFA is
      a scalp EEG marker of epileptic networks with the advantage of being recorded non
      invasively during interictal non-REM sleep.

PMID- 18804957
TI  - History and seizure semiology in distinguishing frontal lobe seizures and
      temporal lobe seizures.
AB  - This study aimed to determine the reliability of clinical history and seizure
      semiology for distinguishing between frontal lobe seizures (FLS) and temporal
      lobe seizures (TLS). FLS patients (n=23) were consecutively identified through an
      epilepsy surgery database. TLS patients (n=27) were selected randomly from 238
      patients who had undergone temporal lobe surgery for epilepsy. The criterion
      standard for seizure localization was the location of resective epilepsy surgery
      that controlled seizures for a minimum of 2 years. Blinded comparisons of 13
      historical information items (HII) and 19 video-recorded semiologic features
      (VSF) were made. We identified 3 HII (sex, history of febrile convulsions, and
      history of generalized tonic-clonic seizures) and 2 VSF (fencing posturing and
      postictal confusion) that significantly distinguished between FLS and TLS. The
      multivariate analysis model correctly identified 87% of FLS patients and 74% of
      TLS patients. No single HII or VSF is sufficient for distinguishing between FLS
      and TLS. A model integrating multiple HII and VSF may assist in this
      differentiation, but some patients still may be misclassified.

PMID- 18804958
TI  - Response to diazepam in children with malaria-induced seizures.
AB  - Malaria infection reduces the binding capacity of benzodiazepine receptors in
      mice. We studied the efficacy of diazepam terminating seizures in children with
      falciparum malaria. Diazepam stopped seizures in fewer patients with malaria
      parasitaemia (chi(2)=3.93, P=0.047) and those with clinical diagnosis of malaria
      (chi(2)=9.84, P=0.002) compared to those without. However malaria was not
      identified as an independent risk factor for diazepam's failure to stop seizures
      in children.

PMID- 18804959
TI  - A DTI study of white matter microstructure in individuals at high genetic risk
      for schizophrenia.
AB  - Structural brain developmental anomalies, particularly those in frontotemporal
      white matter pathways, may have a genetic component and place people at increased
      risk for schizophrenia. The current study employed Diffusion Tensor Imaging (DTI)
      to measure fractional anisotropy (FA) as a quantitative indicator of white matter
      integrity. We examined twenty-two participants at high genetic risk for
      schizophrenia (HR), 23 people with schizophrenia (most of whom were family
      members of those at HR) and 37 non-psychiatric controls for comparison. In those
      at HR, reduced FA was observed in the cingulate and angular gyri bilaterally. In
      a few regions, FA was higher in HR participants than in comparison participants.
      These regional variations in FA might reflect differences in white matter
      development from comparison participants. Our data provide some evidence that
      abnormal white matter integrity may be detectable before the onset of a psychotic
      illness, although longitudinal studies are necessary to determine whether these
      individuals at genetic risk with abnormal FA will develop illness and whether
      these changes are associated with the genetic risk for the disorder.

PMID- 18804960
TI  - Novel rating scales for schizophrenia - Targeted Inventory on Problems in
      Schizophrenia (TIP-Sz) and Functional Assessment for Comprehensive Treatment of
      Schizophrenia (FACT-Sz).
AB  - OBJECTIVE: Many rating scales have been in use to evaluate various symptomatic
      domains, and eventually there are too many scales to be selected and widely
      utilized in busy real-world settings. Relevant, quick, and user-friendly
      assessment scales are needed to facilitate measurement-based treatment of
      schizophrenia. METHODS: The authors created unique convenient assessment scales:
      Targeted Inventory on Problems in Schizophrenia (TIP-Sz), and Functional
      Assessment for Comprehensive Treatment of Schizophrenia (FACT-Sz). The TIP-Sz
      consists of 10 items (behavioral dyscontrol/disorganization,
      hostility/agitation/violence, indifference/affective withdrawal/motor
      retardation, symptoms on mood/anxiety/obsession/compulsion, insight/reality
      testing, social competence/independence, adherence to treatment, therapeutic
      alliance/comfort of therapists on the situation, overall prognostic impression,
      and subjective well-being/satisfaction with therapy). They are all common and
      frequently problematic, and each item is rated from 0-10. The FACT-Sz evaluates
      psychosocial functioning of patients with a score of 0-100, and is judged
      entirely on an objective basis. Their correlations with the frequently utilized
      Positive and Negative Syndrome Scale (PANSS), Global Assessment of Functioning
      (GAF), and Clinical Global Impression-Severity subscale were determined. RESULTS:
      Data on 36 patients, assessed separately by four experienced psychiatrists, were
      analyzed. Under an excellent interrater reliability among raters (Intraclass
      correlation coefficients: 0.822-0.966), correlations among the scales were very
      high (Spearman's rho: 0.825-0.909), and other indicators of the scale were
      generally good. Specifically, the TIP-Sz and FACT-Sz could be rated at 1/3-1/4 of
      time to complete the PANSS and GAF. CONCLUSION: The TIP-Sz and FACT-Sz proved to
      be reliable and valid, which would be of value in daily clinical practice as a
      minimum standardized assessment set.

PMID- 18804961
TI  - Successful acamprosate treatment of alcohol dependence in schizophrenia.

PMID- 18804962
TI  - Overexpression of the fibroblast growth factor receptor 2-IIIc in Kaposi's
      sarcoma.

PMID- 18804963
TI  - Immunohistological analysis of peptide-induced delayed-type hypersensitivity in
      advanced melanoma patients treated with melanoma antigen-pulsed mature monocyte
      derived dendritic cell vaccination.
AB  - BACKGROUND: In melanoma patients vaccinated with monocyte-derived melanoma
      peptide-pulsed dendritic cells (DC), the delayed-type hypersensitivity (DTH)
      reactions have been examined as a surrogate marker to determine if acquired
      immunity is induced by DC vaccination. To date, however, only limited information
      has been reported as for histopathological analyses of DTH. OBJECTIVE: To
      evaluate tumor-specific immunomonitoring histopathologically after DC vaccination
      in melanoma patients. METHODS: Seven patients previously vaccinated with monocyte
      derived melanoma peptide-pulsed DCs were challenged with recall antigenic peptide
      injection in the skin of the forearm. Using immunohistochemical techniques, the
      presence of immune cells and the expression of CD4, CD8, interleukin (IL)-2, IL
      4, IL-10, Foxp3, CD1a, CD1d, and interferon (IFN)-gamma was investigated at the
      site of injection where a DTH reaction developed. RESULTS: Strong DTH reactions
      from infiltrated erythema to bullae formation were detected in all 7 cases.
      Biopsies taken from the DTH site revealed heavy infiltration of mononuclear cells
      and eosinophils in the dermis and subcutaneous tissue. Cells staining positively
      for CD4, CD8, IL-2, IL-4, Foxp3, CD1d, and IFN-gamma were increased at the site
      48h after antigen injection in all cases. Cells positive for IL-10 were never
      found in any patient. Regulatory T cells appeared 6h after injection and reached
      their maximum at day 7. CONCLUSIONS: The significant induction of CD8(+)T cells
      as well as both Th1 and Th2-type cells at the site of DTH suggests that effective
      antigen presentation leading to anti-tumor immune responses has taken place.
      Inhibitory mechanisms may also develop as the disappearance of the DTH response
      could be related to an increase in Foxp3+ cells.

PMID- 18804964
TI  - Keratin alterations could be an early event of wrinkle formation.

PMID- 18804965
TI  - In vitro activity of cidofovir against the emerging Cantagalo virus and the
      smallpox vaccine strain IOC.
AB  - The antiviral effect of cidofovir was evaluated against two strains of vaccinia
      virus: the field strain Cantagalo virus (CTGV) and the smallpox vaccine IOC. The
      drug severely inhibited virus replication, revealing an EC(50) (drug
      concentration required to inhibit 50% of virus replication) of 7.68 microM and
      9.66 microM, respectively, for CTGV and vaccine strain IOC. Similarly, other
      field isolates of Cantagalo-like viruses recently collected in distinct outbreaks
      were equally sensitive to the drug. Pre-treatment of cells prior to infection
      effectively established an antiviral state, inhibiting virus replication by >90%
      after 24h in the absence of cidofovir. CTGV infections represent an emerging
      zoonosis, and outbreaks have been frequently reported in several states of
      Brazil. Also, the possibility of resuming the manufacture of smallpox vaccine
      supports the need to evaluate the effect of antiviral drugs on the Brazilian
      vaccine strain IOC. As there is no currently approved antipoxvirus therapy, our
      data are extremely encouraging.

PMID- 18804966
TI  - Molecular characterisation of the metallo-beta-lactamase genes in imipenem
      resistant Gram-negative bacteria from a university hospital in southern Taiwan.
AB  - In this study, 260 non-replicate imipenem-resistant Gram-negative bacteria
      isolated between January 2002 and December 2006 were subjected to a screening
      test for detection of metallo-beta-lactamase (MBL) using the Etest containing
      imipenem and ethylene diamine tetra-acetic acid (EDTA). Among the 260 strains,
      123 (47.3%) appeared to produce MBL. Of these 123 strains, 113 (91.9%) were found
      by polymerase chain reaction (PCR) to carry MBL genes of types blaVIM-2, blaVIM
      3, blaVIM-11 (blaVIM-11a), blaIMP-8 and novel blaIMP-24. One strain of Serratia
      marcescens harboured two MBL genes (blaVIM-11 and blaIMP-8) simultaneously. Of
      the 123 strains, 116 strains (94.3%) carrying the intI1 gene and 21 strains
      carrying integron-associated blaVIM-3, blaVIM-11 and blaIMP-8 genes were
      identified among Acinetobacter baumannii, Pseudomonas aeruginosa, Acinetobacter
      haemolyticus and S. marcescens. Using pulsed-field gel electrophoresis (PFGE) and
      Southern hybridisation with the blaVIM gene probe for I-CeuI-digested genomic
      DNA, P. aeruginosa 9527 strain harboured two class 1 integron-associated MBL
      genes in the chromosome, including blaVIM-3-orf2-aacA4 and novel bla(VIM-3)-orf2
      aacA4-aadB-aacA4. This is the first description of the blaVIM-11 gene spreading
      among P. aeruginosa and A. baumannii strains in southern Taiwan. This finding
      suggests that clinical spread of this blaVIM-11 gene is a matter of great concern
      for carbapenem resistance in southern Taiwan.

PMID- 18804967
TI  - Changes in glucose metabolism due to aging and gender-related differences in the
      healthy human brain.
AB  - Using [(18)F]fluoro-deoxy-glucose-PET, we studied relative metabolic changes due
      to age- and gender-related differences in the brain of 126 healthy subjects from
      their twenties to seventies. We used a data-extraction technique, the three
      dimensional stereotactic surface projections (3D-SSP) method, to measure
      metabolic changes with fewer effects of regional anatomic variances. Simple
      regression analysis revealed significant age-related increases in relative
      metabolic values in the parahippocampal and amygdala regions in both sexes in
      their twenties to forties, and significant age-related decreases in both sexes in
      their fifties to seventies. Relative values in the frontal lobe showed
      significant age-related decreases in both sexes in their twenties to forties, but
      these effects were not seen in subjects in their fifties to seventies.
      Significant gender differences in correlation coefficients of relative values
      with age were shown in the parahippocampal, primary sensorimotor, temporal,
      thalamus and vermis regions in subjects in their 20s to 40s, but disappeared in
      subjects in their twenties to forties, but were not apparent in subjects in their
      fifties to seventies except in the vermis. Males in their twenties to sixties and
      females in their fifties showed significant laterality in relative values in the
      temporal lobes. Our study demonstrated age- and gender-related differences in
      glucose metabolism in healthy subjects.

PMID- 18804968
TI  - Ion selectivity, transport properties and dynamics of amphotericin B channels
      studied over a wide range of acidity changes.
AB  - Amphotericin B (AmB) is an antifungal antibiotic which, despite the severe side
      effects, is still used for the treatment of systemic fungal infections. Herein we
      studied the influence of pH upon the selectivity and the transport properties of
      AmB channels inserted in reconstituted, ergosterol-containing zwitterionic lipid
      membranes. Our electrophysiology experiments carried out on single and multiple
      AmB channels prove that at pH 2.8 these channels are anion selective, whereas at
      neutral and alkaline pH's (pH 7 and pH 11) they become cation selective. We
      attribute this to the pH-dependent ionization state of the carboxyl and amino
      groups present at the mouth of AmB molecules. Surprisingly, our data reveal that
      the single-molecule ionic conductance of AmB channels varies in a non-monotonic
      fashion with pH changes, which we attribute to the pH-dependent variation of the
      surface and dipole membrane potential. We demonstrate that when added only from
      one side of the membrane, in symmetrical salt solutions across the membrane and
      low pH values, AmB channels display a strong rectifying behavior, and their
      insertion is strongly favored when positive potentials are present on the side of
      their addition.

PMID- 18804969
TI  - Fluorescent sensor responsive to local viscosity and its application to the
      imaging of liquid-ordered domain in lipid membranes.
AB  - A novel fluorescent sensor responsive to local viscosity in the lipid bilayer
      membranes was designed and synthesized. The sensor changes its fluorescence
      intensity reflecting the local viscosity of its surrounding medium. The
      fluorescence measurement showed that the sensor is capable of discriminating
      between different phase states of lipid bilayer. In addition, the sensor
      visualized liquid-ordered microdomains on giant vesicles in terms of the
      microviscosity with a simple fluorescence technique.

PMID- 18804970
TI  - Dualistic acidic and neutral glucose fermentation balance in small intestine:
      Simulation in vitro.
AB  - Intestinal microbes live in diminished or deprived oxygen conditions. Facultative
      anaerobic bacteria of the family Enterobacteriaceae ferment glucose in the gut
      using two main pathways: mixed acid and neutral fermentations. The aim of the
      present study was to clarify the roles of these fermentations in an in vitro
      model. Acid-producing Escherichia coli ATCC 25922 and neutral end-products
      producing Klebsiella mobilis ATCC 13048 were cultured in a Portable Microbe
      Enrichment Unit (PMEU) which permitted the selection of the gas phase in
      standardized conditions. In the butanediol production experiments also Klebsiella
      pneumoniae ssp. pneumoniae IIIa2 E111 strain was also used. Two isomers of 2,3
      butanediol were observed in both aerobic and microaerobic Klebsiella cultures.
      During 7h cultures both E. coli and K. mobilis grew from densities of some
      million up to some billions per ml. The growth was almost equal in both aerobic
      and microaerobic conditions. In anaerobic conditions a balance prevailed in mixed
      E. coli and Klebsiella cultures between the species (final pH was 5.8-6.1),
      whereas in aerobic conditions the klebsiellas were favoured, and the pH rose up
      to about 8.5 (in 20h) as in pure Klebsiella cultures. In microaerobic Klebsiella
      cultures the final pH varied between 6.7 and 7.5. In mixed cultures the growth
      yields of both bacteria equalled those of the separate pure cultures indicating
      mutual benefits of the co-existence. Apparently E. coli produced a set of organic
      acids, which lowered pH. Klebsiellas increased the pH up to 2units probably due
      to acid conversion in anaerobic conditions to ethanol. We propose that the
      balance of acid and ethanol as well 2,3-butanediol fermentations contributes to
      the small bowel pH regulation, which also aids the host in the nutrient uptake in
      the small intestine.

PMID- 18804971
TI  - [Distal spinal-muscular atrophy 1 (DSMA1 or SMARD1)].
AB  - In this article, we review the clinical, neuropathological and genetic aspects of
      distal spinal-muscular atrophy 1 (DSMA1; MIM#604320), formerly designated as
      autosomal recessive spinal muscular atrophy with respiratory distress type 1
      (SMARD1) and also known as distal hereditary-motor neuropathy type 6 (dHMN6 or
      HMN6).

PMID- 18804972
TI  - [Nebulized corticosteroids and pediatricians: results of the NUAGES survey].
AB  - INTRODUCTION: The aim of the study was to analyze the data of the NUAGES survey
      (a survey on the practice of nebulization in France), concerning the
      prescriptions of nebulized steroids from 514 pediatricians. MATERIAL AND METHODS:
      The reason why nebulization was chosen as a delivery route, the diseases
      motivating the prescription, the age of the patients, the kind of drug used, and
      the prescription and device modalities were studied. RESULTS: Efficacy in
      treating various respiratory diseases was the main reason cited for using
      nebulization, in particular severe persistent asthma (76%). Pediatricians
      prescribed nebulization mainly to infants (60%). The most frequently used drug
      was budesonide suspension (89%), but the intravenous route for steroids (18%) and
      drug admixtures (62%) were also proposed by nebulization. A specific prescription
      for the nebulizer was given in 75% of the cases, with the type of interface to
      use specified in 66%. DISCUSSION: Pediatricians consider that nebulization is
      well adapted to young children. Although the proper steroid is usually chosen,
      unfortunately, it is often prescribed with other drugs, with 1 prescription out
      of 4 not following the recommendations. Prescription of the device is not optimal
      and may compromise the efficacy of the treatment. CONCLUSION: Nebulization is a
      potential mode of delivery for steroids that is difficult to prescribe and
      warrants improved pediatrician training.

PMID- 18804973
TI  - [Capnocytophaga sputigena pleuropneumonitis: a case report].
AB  - Community-acquired pneumonia is complicated by purulent pleural effusion in
      approximately 28% of affected children. Its incidence has increased over the last
      decade. Streptococcus pneumoniae is the most frequent causal microorganism,
      encountered in roughly 80% of cases. We report the case of an immunocompetent 13
      year-old teenager wearing orthodontic braces who suffered from pleuropneumonia
      due to Capnocytophaga sputigena. To date, this Gram-negative bacillus, a
      commensal of the buccal cavity, had never been reported to be responsible for
      pleural or lung infection. The clinical presentation is similar to that observed
      with usual bacteria, while bacterial sensitivity to betalactam antibiotics is
      excellent.

PMID- 18804974
TI  - [Intravenous thrombolysis in pediatric arterial ischemic stroke: a case report
      and a review of the literature].
AB  - Pediatric arterial ischemic stroke (AIS) is little known by pediatricians, as it
      is rare and difficult to diagnose. Current therapeutic approaches include
      platelet aggregation inhibitors, anticoagulation using heparin or thrombolysis
      with rt-PA, and therapeutic abstention in the absence of consensus, in contrast
      with stroke in adults. We report the case of a 3-year-old child who benefited
      from intravenous thrombolysis with rt-PA 2h after a major AIS of the anterior and
      middle left arteries due to embolism from the heart. Neurological progression was
      marked by a persistent, severe functional deficiency, in spite of the early use
      of thrombolysis. No hemorrhagic complication occurred. This observation raises
      the problem of therapeutic indications in childhood AIS and more particularly the
      question of the use of intravenous thrombolysis. Currently, few studies exist on
      this subject and only a few case report of children and teenagers having received
      effective intravenous or intra-arterial thrombolysis further to an AIS are
      available in the literature. A single study describes 46 cases of children with
      AIS having received thrombolysis but reports numerous complications. However, the
      absence of symptomatic hemorrhagic complications is noteworthy. There is
      currently insufficient evidence to recommend thrombolysis in pediatric AIS;
      nevertheless it can be proposed in certain rare cases, similar to the observation
      reported herein.

PMID- 18804975
TI  - [Lung diseases associated with inherited disorders of surfactant metabolism].
AB  - Lung diseases associated with surfactant-metabolism disorders are a heterogeneous
      group of rare diseases. Intra-alveolar accumulation of protein related to
      surfactant dysfunction leads to cough, hypoxemia, and radiological-diffuse
      infiltration. Inherited deficiency of pulmonary surfactant protein B (SP-B) was
      initially described in infants who develop respiratory failure at birth. More
      recently, mutations in other constitutive surfactant proteins, such as surfactant
      protein C or implied in its metabolism, such as ATP-binding cassette, subfamily
      A, member 3 (ABCA3) and thyroid transcription factor 1 (TTF-1) were identified in
      newborns with respiratory distress as well as in children with chronic
      infiltrative pneumonia. The aim of this review is therefore to summarize the
      current state of our knowledge in this area.

PMID- 18804976
TI  - [An uncommon rib tumor in a child: aneurysmal bone cyst].
AB  - The authors report a case of rib aneurysmal-bone cyst in a rachitic 7-year-old
      boy. He had a 6-month history of right-back pain and dyspnea. Pulmonary X-ray and
      computed-tomography scan showed a huge mass located in the 4th right rib
      posterior arch. Right thoracotomy was carried out and complete surgical excision
      of the rib mass was successfully performed. Histological examination confirmed
      the diagnosis. Diagnosis and management of aneurysmal-bone cyst of the rib were
      discussed with a review of the literature.

PMID- 18804977
TI  - [A rare cause of paroxysmal cough with cyanosis in children].

PMID- 18804978
TI  - [Pheochromocytoma revealed by stroke in a child].
AB  - Pheochromocytoma is uncommon in children. We report herein a case in a 6-year-old
      boy whose pheochromocytoma was revealed by cerebral ischemia as a consequence of
      acute-cardiac failure. Twenty-four-hour urinary catecholamines were markedly
      increased. Abdominal ultrasonography and computed tomography located the tumor on
      the left adrenal gland. After surgical excision, hypertension disappeared.
      Diagnosis and treatment of pheochromocytoma in children are discussed.

PMID- 18804979
TI  - [Distribution of neutralizing measles serum antibodies according to age in women
      of childbearing age in France in 2005-2006].
AB  - Measles-vaccine coverage (MVC) increased significantly only beginning in 1983
      based on the official recommendations. The majority of women born after 1983
      should have vaccine-acquired rather than naturally derived immunity. Passively
      transferred measles antibodies (Mab) are expected to provide protection to
      offsprings during their 1st few months of life. OBJECTIVE: Compare neutralizing
      Mab titers according to age in women aged 12-40 years, i.e., born before and
      after 1983. METHODS: A multicenter seroepidemiological study was conducted in
      France in 2005-2006; 210 outpatient or hospitalized women were enrolled and
      classified into 4 age groups (12-18, 19-22, 23-30, and 31-40 years). Mab titers
      were assessed using a reference plaque reduction neutralization assay (protection
      threshold > 120 mIU/ml). RESULTS: Ninety-four percent of subjects had a Mabs
      titer greater than 120 mIU/ml. Women born before 1983 had significantly higher
      geometric mean titers (GMTs) of Mabs than those born after 1983(1358 mIU/ml vs.
      731 mIU/ml [p<0.001]). The comparison of the 4 cohorts showed a significant
      decrease (p<0.001) in GMTs of Mab in the female population with increasing age
      (670, 771, 1173, and 1821 mUI/ml, respectively, in the 12-18, 19-22, 23-30, and
      31-40 years age groups). For the 1st time in France, we show in women of
      childbearing age that in 2005-2006 neutralizing Mab GMTs were far above
      protective threshold for all age groups. Women in younger age groups (with high
      MVC) have significantly lower Mab titers. A lower passive transfer of Mab to
      their offsprings could result in a shorter period of measles protection and
      question the measles vaccine 1st dose at 1 year.

PMID- 18804980
TI  - [Six-month pediatric residency in Hanoi].

PMID- 18804981
TI  - [Gastroschisis and necrotizing enterocolitis].

PMID- 18804982
TI  - Discrimination ability of individual measures used in sleep stages
      classification.
AB  - OBJECTIVE: The paper goes through the basic knowledge about classification of
      sleep stages from polysomnographic recordings. The next goal was to review and
      compare a large number of measures to find the suitable candidates for the study
      of sleep onset and sleep evolution. METHODS AND MATERIAL: A huge number of
      characteristics, including relevant simple measures in time domain,
      characteristics of distribution, linear spectral measures, measures of complexity
      and interdependency measures were computed for polysomnographic recordings of 20
      healthy subjects. Summarily, all-night evolutions of 818 measures (73
      characteristics for various channels and channel combinations) were analysed and
      compared with visual scorings of experts (hypnograms). Our tests involved
      classification of the data into five classes (waking and four sleep stages) and
      10 classification tasks to distinguish between two specific sleep stages. To
      discover measures of the best decision-making ability, discriminant analysis was
      done by Fisher quadratic classifier for one-dimensional case. RESULTS AND
      CONCLUSIONS: The most difficult decision problem, between S1 and REM sleep, were
      best managed by measures computed from electromyogram led by fractal exponent
      (classification error 23%). In the simplest task, distinction between wake and
      deep sleep, the power ratio between delta and beta band of electroencephalogram
      was the most successful measure (classification error 1%). Delta/beta ratio with
      mean classification error 42.6% was the best single-performing measure also in
      discrimination between all five stages. However, the error level shows
      impossibility to satisfactorily separate the five sleep stages by a single
      measure. Use of a few additional characteristics is necessary. Some novel
      measures, especially fractal exponent and fractal dimension turned up equally
      successful or even superior to the conventional scoring methods in discrimination
      between particular states of sleep. They seem to provide a very promising basis
      for automatic sleep analysis particularly in conjunction with some of the
      successful spectral standards.

PMID- 18804983
TI  - Association of genetic profiles to Crohn's disease by linear combinations of
      single nucleotide polymorphisms.
AB  - MOTIVATIONS: A large number of single nucleotide polymorphisms (SNPs) are
      supposed to be involved in onset, differentiation and development of complex
      diseases. Univariate analysis is limited in studying complex traits since does
      not take into account gene-gene interaction, and the correlation of multiple SNPs
      with a specific phenotype. Moreover it might underestimate gene variants with
      weaker genetic contribution. Therefore more sophisticated techniques should be
      adopted when investigating the role of a panel of genetic markers in disease
      predisposition. METHODS: In this paper we describe a general method to
      simultaneously investigate the association between SNPs profile and Crohn's
      disease (CD), by evaluating the susceptibility or protective role of single or
      groups of markers. As an association measure we adopted a weighted linear
      combination of SNPs in which suitable weighting vectors belonged to predefined
      and over-complete vocabularies of vectors (frames), or were determined by the
      data. RESULTS: The proposed method found a weighted linear combination of SNPs
      statistically associated to CD (p=3.81 x 10(-10)) describing the role of the
      markers in the pathology. In particular, MCP1-A2518G gave the major contribution
      as protective locus, similarly to TNF-alpha-C857T, DLG5 rs124869, PTPN22 C1858T
      variants. The NF kappaB -94ATTG variants was found to be irrelevant for CD. For
      the remaining markers, a susceptibility role was attributed also confirming that
      markers on CARD15 gene, in particular G908R and L1007fsinsC, are involved with CD
      to the same extent as FcGIIIA G559T and TNF-alpha-G308A. Moreover, an odds ratio
      of 3.99(p<1.0 x 10(-4)) was assigned to this combination which is greater than
      the best odds ratio found in the single SNP analysis. CONCLUSIONS: Our
      methodology allowed to statistically measure the association of a panel of SNPs
      with a specific phenotype. Therefore this approach could be suitable for a
      population screening program with simultaneous evaluation of a large set of gene
      polymorphism.

PMID- 18804984
TI  - Relationship between n-3 and n-6 plasma fatty acid levels and insulin resistance
      in coronary patients with and without metabolic syndrome.
AB  - BACKGROUND AND AIMS: Animal studies show that ecosapentaenoic acid (EPA) and
      docosahexaenoic acid (DHA) are effective for the prevention and treatment of
      insulin resistance (IR). Data from human studies are contradictory. We sought to
      determine whether the relationships between plasma n-3 and n-6 polyunsaturated
      fatty acid (FA) levels and IR differ according to the presence or absence of
      metabolic syndrome (MS) in a coronary heart disease sample. METHOD AND RESULTS:
      Clinical, metabolic parameters, plasma phospholipid FA profiles and indirect
      measurement of IR (homeostatic model assessment-HOMA) were measured in 734
      subjects, 8 weeks following acute coronary syndrome. FA levels and their
      correlations with IR were compared in subjects with and without MS. MS patients
      had higher saturated (16:0, 18:0) and n-6 (18:3n-6, 20:3n-6, 22:4n-6, 22:5n-6) FA
      levels, and lower EPA and DHA levels. HOMA-IR correlated positively with total
      saturated (r=0.13, P=0.017) and n-6 (r=0.17, P=0.001) FA levels and negatively
      with total n-3 FA levels (r=-0.13, P=0.012), in MS subjects only. Total n-3 and n
      6 FAs and n-6/n-3 ratio were associated with HOMA-IR levels in MS subjects
      independent of total saturated FA levels, age, sex, sedentary behaviour, smoking,
      waist circumference, triglycerides, HDL-cholesterol, and systolic blood pressure.
      CONCLUSIONS: Relationships between polyunsaturated FA type and IR vary according
      to the presence or absence of MS. N-3 FAs including EPA and DHA are associated
      with lower HOMA-IR, while the opposite is true for n-6 FAs. Prospective studies
      are required to address the potential effects of intermediate dose EPA and DHA on
      glucose handling in MS patients.

PMID- 18804985
TI  - The effect of a short-term hypocaloric diet on liver gene expression and
      metabolic risk factors in obese women.
AB  - BACKGROUND AND AIMS: Most gene expression studies examining the effect of obesity
      and weight loss have been performed using adipose tissue. However, the liver also
      plays a central role in maintaining energy balance. We wanted to study the
      effects of a hypocaloric diet on overall hepatic gene expression and metabolic
      risk factors. METHODS AND RESULTS: The study subjects were middle-aged, obese
      women. The diet intervention subjects (n=12) were on a hypocaloric, low-fat diet
      for 8 weeks with a daily energy intake of 5.0 MJ (1200 kcal), while the control
      subjects (n=19) maintained their weight. Liver biopsies were taken at the end of
      the diet period during a gallbladder operation. Hepatic gene expression was
      analyzed using microarrays by comparing the gene expression profiles from four
      subjects per group. A global decrease in gene expression was observed with 142
      down-regulated genes and only one up-regulated gene in the diet intervention
      group. The diet resulted in a mean weight loss of 5% of body weight. Triglyceride
      and fasting insulin concentrations decreased significantly after the diet.
      CONCLUSIONS: The global decrease in hepatic gene expression was unexpected but
      the results are interesting, since they included several genes not previously
      linked to weight reduction. However, since the comparison was made only after the
      weight reduction, other factors in addition to weight loss may also have been
      involved in the differences in gene expression between the groups. The decrease
      in triglyceride and fasting plasma insulin concentrations is in accordance with
      results from previous weight-loss studies.

PMID- 18804986
TI  - Evaluating endothelial function of the common carotid artery: an in vivo human
      model.
AB  - BACKGROUND AND AIMS: Flow mediated dilation (FMD) of peripheral conduit arteries
      is a well-established tool to evaluate endothelial function. The aims of this
      study are to apply the FMD model to cerebral circulation by using acetazolamide
      (ACZ)-induced intracranial vasodilation as a stimulus to increase common carotid
      artery (CCA) diameter in response to a local increase of blood flow velocity
      (BFV). METHODS AND RESULTS: In 15 healthy subjects, CCA end-diastolic diameter
      and BFV, middle cerebral artery (MCA) BFV and mean arterial blood pressure (MBP)
      were measured at basal conditions, after an intravenous bolus of 1g ACZ, and
      after placebo (saline) sublingual administration at the 15th and 20th minute. In
      a separate session, the same parameters were evaluated after placebo (saline)
      infusion instead of ACZ and after 10 microg/m(2) bs and 300 microg of glyceryl
      trinitrate (GTN), administered sublingually, at the 15th and 20th minute,
      respectively. After ACZ bolus, there was a 35% maximal MCA mean BFV increment
      (14th minute), together with a 22% increase of mean CCA end-diastolic BFV and a
      CCA diameter increment of 3.9% at the 3rd minute (p=0.024). There were no MBP
      significant variations up to the 15th minute (p=0.35). After GTN administration,
      there was a significant increment in CCA diameter (p<0.00001). CONCLUSIONS: ACZ
      causes a detectable CCA dilation in healthy individuals concomitantly with an
      increase in BFV. Upon demonstration that this phenomenon is endothelium
      dependent, this experimental model might become a valuable tool to assess
      endothelial function in the carotid artery.

PMID- 18804987
TI  - Heart rate behavior during an exercise stress test in obese patients.
AB  - BACKGROUND AND AIMS: Heart rate (HR) response to exercise has not been fully
      described in the obese. We wanted to study the differences between obese and non
      obese patients in HR behavior during an exercise stress test and to determine
      whether these differences influence exercise capacity. METHODS AND RESULTS: We
      studied 554 patients (318 females) who underwent a treadmill exercise test. All
      subjects were in sinus rhythm. Patients with ischemic heart disease, with reduced
      ejection fraction and patients taking drugs that interfere with HR were excluded.
      The population included 231 patients with BMI<30 kg/m(2) (group 1), 212 patients
      who were unfit and obese (group 2) and 111 patients who were trained obese (group
      3). Resting HR was similar in the various groups. Peak HR, HR recovery and
      chronotropic index were lower in obese subjects, regardless of their fitness
      level. Multivariate analysis showed that HR related variables were associated
      with age, BMI, height, hypertension and various pharmacologic treatments, while
      exercise capacity was strongly dependent on HR behavior, as well as on sex, age,
      BMI and diabetes. CONCLUSION: Obese subjects have a marked impairment of HR
      behavior during exercise and in the recovery period, and the blunted increase in
      HR is the most important factor that influences exercise capacity.

PMID- 18804988
TI  - Altered monocyte CD44 expression in peripheral arterial disease is corrected by
      fish oil supplementation.
AB  - BACKGROUND AND AIMS: CD44 and its splice variants can be expressed on all
      leukocytes, conferring adhesive properties and enhancing cellular recruitment to
      the endothelium during inflammation. CD44 expression is increased in inflammatory
      conditions such as rheumatoid arthritis and CD44 variant 3 (CD44v3) expression
      may be associated with inflammation. We have examined CD44 and CD44v3 expression
      on peripheral blood monocytes from patients with peripheral arterial disease
      (PAD) and healthy controls. We have also examined the effect of fish oil
      supplementation on these markers. METHODS AND RESULTS: CD44 and CD44v3 were
      assessed at baseline and following dietary supplementation with fish oil for 12
      weeks in both PAD and control groups. Monocytes from PAD patients had higher CD44
      expression than those from controls (median intensity fluorescence (MIF): 480+/
      278 vs 336+/-251 (mean+/-SD); p<0.001). Following 12 weeks' dietary
      supplementation with fish oil, CD44 expression was reduced in PAD patients (MIF:
      480+/-278 vs 427+/-262; p=0.05) but not in controls (336+/-251 vs 355+/-280; ns).
      Monocyte CD44v3 expression was lower in cultured monocytes from PAD patients
      compared to those from controls (0.15+/-0.15 vs 0.22+/-0.14 OD units; p<0.02).
      This was increased in the PAD group following fish oil supplementation (0.15+/
      0.14 to 0.27+/-0.23 OD units; p<0.001). CONCLUSION: Monocyte CD44 and CD44v3
      expression are altered in arterial disease but are returned towards levels seen
      in control subjects by dietary fish oil supplementation.

PMID- 18804989
TI  - Adiponectin and cardiovascular risk prediction: can the ambiguities be resolved?

PMID- 18804990
TI  - Implementing China's circular economy concept at the regional level: a review of
      progress in Dalian, China.
AB  - The circular economy (CE) concept was introduced in China to address
      environmental degradation and resource scarcity associated with rapid economic
      development. Chosen as a demonstration city, Dalian has implemented the CE
      strategy as a means of conserving water, materials, energy and land. This paper
      outlines some of the regional CE initiatives that have been successful to date in
      Dalian, including those focusing on conserving energy and water resources and
      others focusing on reduced industrial emissions. The paper details the approach
      used in implementing the CE concept in Dalian, tracing the foci and goals of the
      program, and the sectoral approach used to implement a CE. Although Dalian
      municipality has achieved many successes in implementing a CE, our paper
      identifies several challenges that, until recently, have held back complete
      implementation. These include: the lack of incentives for older industries to
      'green' their operations, the lack of financial support to expand the CE concept,
      and a broad-based need for heightened public awareness and participation in CE
      initiatives. Our paper then identifies several responses by Dalian municipality
      to overcome these challenges, including pricing and tax reforms that serve as
      conservation incentives, the provision of financial support for CE promotion
      through budget reorganization, and the organization of CE training programs. Our
      paper concludes that, although CE initiatives have been successful in Dalian,
      more is possible and more is needed before Dalian can be designated a true 'eco
      city'. The approach used by Dalian can provide guidance for other Chinese cities,
      although it is recognized that each city must tailor its own approach for
      differing contexts and conditions.

PMID- 18804991
TI  - Feasibility of incorporating waste grass clippings (Lolium perenne L.) in
      particleboard composites.
AB  - This study investigated some of the important physical (thickness swelling) and
      mechanical (modulus of rupture, modulus of elasticity and internal bond)
      properties of single-layer particleboard panels made from eucalyptus (Eucalyptus
      camaldulensis Dehn.), waste of grass clippings (Lolium perenne L.) and
      combinations of the two. The chemical properties (pH, holocelluse and alpha
      cellulose contents, and water, alcohol-benzene and 1% sodium hydroxide
      solubilities) of the raw materials were also determined. Panels with a 6:94 ratio
      of grass-to-eucalyptus particles had the required mechanical properties for
      interior fitments including furniture and general uses. Boards manufactured with
      100% grass clippings exhibited the lowest quality. The overall panel properties
      improved with a lower percentage of grass clippings added. Based on initial
      results, it also appears that grass should compose no more than 13% to achieve
      acceptable panel properties for interior fitments and general uses.

PMID- 18804992
TI  - The implementation of PAYT system under the condition of financial balance in
      France.
AB  - Since 2005, France has been facing a reform of the financial regulation of the
      management of municipal solid waste, by tax or flat fees. Nevertheless, the
      application of unit pricing is limited to about 15 local authorities, but
      interest is expanding. The French examples confirm the efficiency of this PAYT
      system. The prevention and the sorting of packaging waste are increasing and the
      quantity of residual waste falling. But, we have highlighted the difficulty for
      the local authorities to balance their budgets during the years of PAYT system
      implementation. After a short review of the situation in France of the financing
      of waste services, and in particular of PAYT system, the paper presents, firstly
      the financial model and then, the results of its application in two communities.
      The cost model takes into account the expenditure of management on various waste
      flows and the revenues for the sale of by-products. A financial balance is
      ensured by the payments from households. Consequently, the unit pricing and the
      effect of the behaviour of the inhabitants are introduced into the simulation
      model. The application on two local authorities showed that the increase of
      sorting waste did not restore the balance. From the analysis, three reasons
      explain this situation: Thus, the development of the tariff must be carried out
      according to an economic approach. In the end, after the presentation of the
      financial modelling and its application, we make recommendations to aid the
      implementation of the PAYT system and the development of the pricing structures
      by local authorities.

PMID- 18804993
TI  - A new amperometric nanostructured sensor for the analytical determination of
      hydrogen peroxide.
AB  - A new amperometric, nanostructured sensor for the analytical determination of
      hydrogen peroxide is proposed. This sensor was constructed by immobilizing silver
      nanoparticles in a polyvinyl alcohol (PVA) film on a platinum electrode, which
      was performed by direct drop-casting silver nanoparticles that were capped in a
      PVA colloidal suspension. UV-vis spectroscopy, X-ray diffraction and transmission
      electron microscopy were used to give a complete characterization of the
      nanostructured film. Cyclic voltammetry experiments yielded evidence that silver
      nanoparticles facilitate hydrogen peroxide reduction, showing excellent catalytic
      activity. Moreover, the cronoamperometric response of modified sensors was
      dependent on nanoparticle lifetime. Experiments were performed, using freshly
      prepared solutions, after 4 and 8 days. Results concerning the quantitative
      analysis of hydrogen peroxide, in terms of detection limit, linear range,
      sensitivity and standard deviation (STD), are discussed for each tested sensor
      type. Utilization of two different linear ranges (40 microM to 6mM and 1.25
      microM to 1.0mM) enabled the assessment of concentration intervals having up to
      three orders of magnitude. Moreover, the electrode made using a 4-day-old
      solution showed the maximal sensitivity of 128 nA microM(-1)(4090 nA microM(
      1)cm(-2)), yielding a limit of detection of 1 microuM and STD of 2.5 microAmM(
      1). All of these analytical parameters make the constructed sensors suitable for
      peroxide determination in aqueous solution.

PMID- 18804994
TI  - Direct electron transfer of Horseradish peroxidase on porous structure of screen
      printed electrode.
AB  - Disposable hydrogen peroxide biosensor was developed based on the direct electron
      transfer of horseradish peroxidase (HRP) on porous screen-printed carbon
      electrodes. Conventional screen-printing process was manually performed to
      fabricate the planar carbon electrodes, which were endowed with porous surfaces
      especially after anodizing pretreatment. The cyclic voltammetry experiment
      indicated a pair of stable and well-defined redox peaks with a formal potential
      of -0.33 V. And the formal potential was pH-dependent, having a slope of -55.2
      mV/pH which indicated one electron transfer. The heterogeneous electron transfer
      rate constant k(s) was estimated to be 13.28+/-4.80s(-1). Additionally, the
      sensitivity was 143.3 mAM(-1)cm(-2) and the linear range was from 5.98 to 35.36
      microM. In conclusion, the present work achieved the direct electron transfer of
      HRP on screen-printed electrodes without any promoters. The porous structure of
      screen-printed carbon electrodes facilitated the direct electron transfer between
      the active sites of HRP and the electrodes due to large amounts of conductive
      sites available on the surface for contacting with enzyme molecules. Moreover,
      the proposed biosensor could be mass-produced at low price, promising for
      commercial application.

PMID- 18804995
TI  - Improvement of the anodic bioelectrocatalytic activity of mixed culture biofilms
      by a simple consecutive electrochemical selection procedure.
AB  - In this paper we demonstrate that the anodic, bioelectrocatalytic performance of
      wastewater inoculum based, mixed culture microbial biofilms can be considerably
      improved by using a consecutive, purely electrochemical selection and biofilm
      acclimatization procedure. The procedure may represent an alternative to a
      repetitive mechanical biofilm removal, re-suspension and electrochemically
      facilitated biofilm formation. By using the proposed technique, the
      bioelectrocatalytic current density was increased from the primary to the
      secondary biofilm from 250 microAcm(-2) to about 500 microAcm(-2); and the power
      density of respective microbial fuel cells could be increased from 686 mWm(-2) to
      1487 mWm(-2). The electrochemical characterization of the biofilms reveals a
      strong similarity to Geobacter sulfurreducens biofilms, which may indicate a
      dominating role of this bacterium in the biofilms.

PMID- 18804996
TI  - Phase-I-study of four different schedules of pemetrexed, gemcitabine and
      cisplatin in patients with locally advanced or metastatic solid tumours.
AB  - This non-randomised Phase-I-study determined recommended dose (RD) and dose
      limiting toxicities (DLTs) of four different schedules combining pemetrexed (P),
      gemcitabine (G) and cisplatin (C). Patients 18 years with locally
      advanced/metastatic cancer were enrolled. Doses were escalated for one 21-d (q3w;
      PGC d1, G d8) and three 28-d schedules (q4wA: PG d1, GC d15; q4wB: GC d1, PC d15;
      q4wC: PGC d1+15). Starting doses were P 400/500 mg/m(2) (q3w/q4w), G 800 mg/m(2)
      and C 40 mg/m(2). Sixty patients were enroled (n=12/14/30/4 for
      q3w/q4wA/q4wB/q4wC). Common cancers included head and neck (n=19), prostate
      (n=7), sarcoma (n=5) and stomach (n=5). Thirteen patients experienced DLTs, most
      frequently fatigue (n=4) and neutropenia (n=3). Schedule q4wB reached the highest
      doses (P 600 mg/m(2) d15; G 1250 mg/m(2) d1; C 70 mg/m(2)d1+15). There were no
      CRs, 11 PRs and 25 SDs (n=47). The PGC-combination was feasible. The recommended
      schedule for subsequent studies would be 1250 mg/m(2) G and 60 mg/m(2) C on d1,
      followed by 500 mg/m(2) P and 60 mg/m(2) C on d15.

PMID- 18804997
TI  - First isolated extramedullary relapse in children with B-cell precursor acute
      lymphoblastic leukaemia: results of the Cooprall-97 study.
AB  - We report on the efficiency of treatment of first isolated extramedullary relapse
      of B-cell precursor acute lymphoblastic leukaemia. Sixty-eight children and
      adolescents were included in the trial COPRALL-97. Stratification criteria were
      time to relapse: first complete remission duration of less than 24 months for
      group G3A (n=35), relapse beyond 24 months for group G3B (n=33). Treatment
      consisted of risk-adapted alternating short course multiagent systemic and
      intrathecal chemotherapy and irradiation (18Gy). Event free survival (EFS) and
      overall survival (OS) for all registered patients at 6 years were 43% and 55%,
      respectively. EFS at 4 years for patients of group G3A and G3B were,
      respectively, 31% and 61% (p=0.0071) while OS at 4 years were, respectively, 40%
      and 76% (p=0.065). Our analyses highlighted two independent risks factors
      predictive of decreased EFS: early relapse and age at the initial diagnosis above
      6 years. Early central nervous system relapses have a bad prognosis, and new
      therapeutic strategies are needed.

PMID- 18804998
TI  - Evidence of autonomic dysregulation in otherwise healthy cancer caregivers: a
      possible link with health hazard.
AB  - Caregiving, an important component of cancer patient treatment, may set forth a
      cascade of stress responses such as sympatho-adrenal activation, immuno-humoral
      changes and an unhealthy lifestyle, which could be hazardous to caregivers'
      health. In this observational study, we addressed whether autonomic nervous
      system (ANS) regulation and perception of stress would be altered in a group of
      58 health cancer caregivers as compared to 60 controls. We employed non invasive
      autoregressive spectral analysis of cardiovascular variabilities and ad hoc
      questionnaires. Caregivers show, in addition to signs of psychological
      involvement, a clear autonomic imbalance, suggestive of sympathetic predominance
      at rest and of a reduction of vagal cardiac regulation (overall gain of
      baroreflex -index alpha- was respectively of 17.5+/-1.5 versus 25.1+/-1.8
      msec/mmHg, p<<0.02). These data suggest possible preventive strategies, based on
      tailored treatments aiming at a betterment of individual autonomic profile.

PMID- 18804999
TI  - Maximising recruitment into randomised controlled trials: the role of
      multidisciplinary cancer teams.
AB  - Multidisciplinary cancer teams offer many theoretical benefits, although few have
      been formally examined. This study evaluated the role of multidisciplinary team
      (MDT) meetings in recruitment into randomised controlled trials (RCTs).
      Consecutive MDT patient records were categorised into those with or without a
      recommendation for a national multicentre RCT. Clinical trial office records
      identified whether patients were subsequently screened and randomised. In 125 MDT
      meetings, 350 new patients were discussed, of whom 103 were potentially suitable
      for a RCT. The MDT recommended 68 patients for the trial, of whom 58 (85%) were
      screened for trial eligibility. Of the 35 without an MDT trial recommendation,
      only 23 (66%) were screened (p=0.022). This difference persisted and resulted in
      a greater proportion of MDT recommended patients being recruited (65% versus 49%;
      p=0.12). This study demonstrates that trial recommendation by an MDT
      significantly increases trial screening rates and may improve recruitment.

PMID- 18805000
TI  - The CAP-CR study: direct medical costs in Italian metastatic colorectal cancer
      patients on first-line infusional 5-fluorouracil or oral capecitabine.
AB  - AIM: To describe the healthcare resource consumption of metastatic colorectal
      cancer (MCRC) patients in the Italian healthcare setting. METHODS: A
      retrospective chart analysis estimating direct medical costs of first-line
      infusional 5-Fluorouracil (5-FU) or oral Capecitabine (CAP), associated or not
      with other chemotherapies, from the Italian Healthcare Service (IHCS) and
      Hospital (H) perspectives. RESULTS: 202 subjects were analysed. CAP patients
      (N=66) were older, with a more compromised clinical status and received less
      chemotherapy agents in association than 5-FU patients (N=136). From the IHCS
      perspective, mean total costs per patient were 12,029 euro and 5,781 euro in the
      5-FU and CAP arms respectively; 7,338 euro and 4,688 euro from the H perspective.
      The infusional administration route of 5-FU was a cost driver from both
      perspectives. Sensitivity analyses found the results to be robust to variations
      in base case parameters. CONCLUSIONS: Management of MCRC by oral chemotherapies
      may be an economically advantageous option to both IHCS and hospitals.

PMID- 18805001
TI  - Laparoscopic radical hysterectomy with lymphadenectomy in patients with early
      cervical cancer: our instruments and technique.
AB  - The purpose of this study is to describe the technique of total laparoscopic
      radical hysterectomy (type III procedure) with lymphadenectomy as performed at
      the Advanced Gynecological Endoscopy Center of the Malzoni Medical Center,
      Avellino, Italy. Seventy-seven patients underwent total laparoscopic radical
      hysterectomy (type II, III) with lymphadenectomy between January 2000 and March
      2008. FIGO stage included five patients Ia1 with LVSI (lymph-vascular
      involvement), 24 patients Ia2, and 48 patients Ib1. 60 patients underwent a class
      III procedure and 17 patients a class II procedure according to the Piver
      classification. Histological types included squamous cell carcinoma in 65
      patients, adenocarcinomas in 10 patients, and adenosquamous carcinoma in two.
      Para-aortic lymphadenectomy was performed up to the level of the inferior
      mesenteric artery in eight cases with positive pelvic lymph nodes at frozen
      section evaluation. Total laparoscopic radical hysterectomy can be considered a
      safe and effective therapeutic procedure for the management of early stage
      cervical cancer with a low morbidity; moreover, the laparoscopic route may offer
      an alternative option for patients undergoing radical hysterectomy, although
      multicenter studies and long-term follow-up are required to evaluate the
      oncologic outcomes of this procedure.

PMID- 18805002
TI  - Do earthworms affect dynamics of functional response and genetic structure of
      microbial community in a lab-scale composting system?
AB  - Two laboratory-scale systems were set up (i) composting (without earthworms) and
      (ii) vermicomposting (with earthworms) and were monitored for 60 days after pre
      composting. The physico-chemical parameters (pH, C/N, organic matter, NH(4)(+)-N
      and ash content) showed similar evolution in both systems except a higher
      NH(4)(+)-N in the initial vermicomposts. However, principle component analysis
      (PCA) of enzymatic activities and community level physiological profiles revealed
      differences in the functional response of microbial communities in compost and
      vermicompost during maturation. Dehydrogenase activity and bacterial counts
      indicated a steady decrease in biological activity and population during
      composting, whereas vermicomposting exhibited higher activity on day 30 and a
      reduction in bacterial counts on day 10. PCA of denatured gradient gel
      electrophoresis (DGGE) profiles showed divergent dynamics of bacterial
      communities in two processes. These results indicated differences in the
      functional response and genetic structure of microbial community in composts and
      vermicomposts despite similar changes in their physico-chemical parameters.

PMID- 18805003
TI  - Synthesis and use of sulfonamide-, sulfoxide-, or sulfone-containing
      aminoglycoside-CoA bisubstrates as mechanistic probes for aminoglycoside N-6'
      acetyltransferase.
AB  - Aminoglycoside-coenzyme A conjugates are challenging synthetic targets because of
      the wealth of functional groups and high polarity of the starting materials. We
      previously reported a one-pot synthesis of amide-linked aminoglycoside-CoA
      bisubstrates. These molecules are nanomolar inhibitors of aminoglycoside N-6'
      acetyltransferase Ii (AAC(6')-Ii), an important enzyme involved in bacterial
      resistance to aminoglycoside antibiotics. We report here the synthesis and
      biological activity of five new aminoglycoside-CoA bisubstrates containing
      sulfonamide, sulfoxide, or sulfone groups. Interestingly, the sulfonamide-linked
      bisubstrate, which was expected to best mimic the tetrahedral intermediate, does
      not show improved inhibition when compared with amide-linked bisubstrates. On the
      other hand, most of the sulfone- and sulfoxide-containing bisubstrates prepared
      are nanomolar inhibitors of AAC(6')-Ii.

PMID- 18805004
TI  - Synthesis and biological activity of enantiomeric pairs of 5-[(E)-cycloalk-2
      enylidenemethyl]thiolactomycin congeners.
AB  - The title congeners were synthesized by employing our efficient synthetic route
      previously explored for preparing enantiomeric pairs of thiolactomycin and its 3
      demethyl derivative. While all the synthesized congeners lacked in vitro
      antibacterial activity, some of the congeners bearing an (E)-cyclohept-2
      enylidenemethyl or an (E)-cyclooct-2-enylidenemethyl group were found to exhibit
      more potent type I FAS inhibitory activity than (S)-3-demethylthiolactomycin
      having an unnatural configuration.

PMID- 18805005
TI  - Discovery of a highly orally bioavailable c-5-[6-(4
      Methanesulfonyloxyphenyl)hexyl]-2-methyl-1,3-dioxane-r-2-carboxylic acid as a
      potent hypoglycemic and hypolipidemic agent.
AB  - A series of novel 1,3-dioxane-2-carboxylic acid derivatives containing alkyl
      chain tether and substituted phenyl group as a lipophilic tail have been prepared
      as agonists of PPARalpha and gamma. c-5-[6-(4-Methanesulfonyloxyphenyl)hexyl]-2
      methyl-1,3-dioxane-r-2-carboxylic acid 13c exhibited potent hypoglycemic and
      lipid lowering activity with high oral bioavailability in animal models.

PMID- 18805006
TI  - Synthesis and activity of substituted carbamates as potentiators of the
      alpha4beta2 nicotinic acetylcholine receptor.
AB  - The synthesis and structure-activity relationship of a series of carbamate
      potentiators of alpha4beta2 nAChR is reported herein. These compounds were highly
      selective for alpha4beta2 over other nAChR subtypes. In addition, compounds
      increased the response of alpha4beta2 nAChRs to acetylcholine, as measured with
      patch-clamp electrophysiology.

PMID- 18805007
TI  - Discovery of 4-aryl-2-oxo-2H-chromenes as a new series of apoptosis inducers
      using a cell- and caspase-based high-throughput screening assay.
AB  - As a continuation of our efforts to discover and develop the apoptosis inducing 4
      aryl-4H-chromenes as potential anticancer agents, we explored the removal of the
      chiral center at the 4-position and prepared a series of 4-aryl-2-oxo-2H
      chromenes. It was found that, in general, removal of the chiral center and
      replacement of the 2-amino group with a 2-oxo group were tolerated and 4-aryl-2
      oxo-2H-chromenes exhibited SAR similar to 4-aryl-2-amino-4H-chromenes. The 4-aryl
      2-oxo-2H-chromenes with a N-methyl pyrrole fused at the 7,8-positions were highly
      active with compound 2a having an EC(50) value of 13 nM in T47D cells. It was
      found that an OMe group was preferred at the 7-position. 7-NMe(2), 7-NH(2), 7-Cl
      and 7,8 fused pyrido analogs all had low potency. These 4-aryl-2-oxo-2H-chromenes
      are a series of potent apoptosis inducers with potential advantage over the 4
      aryl-2-amino-4H-chromenes series via elimination of the chiral center at the 4
      position.

PMID- 18805008
TI  - Design, synthesis and structure-activity relationship of simple bis-amides as
      potent inhibitors of GlyT1.
AB  - Several novel classes of potent and small amide-type inhibitors of glycine
      transport (GlyT1) were developed through sequential simplification of a
      benzodiazepinone-lead structure identified from a high-throughput screening. The
      most potent compounds of these structurally simple classes show low nanomolar
      inhibition at the GlyT1 target.

PMID- 18805009
TI  - E2F - at the crossroads of life and death.
AB  - The retinoblastoma tumor suppressor, pRb, restricts cell-cycle progression mainly
      by regulating members of the E2F-transcription-factor family. The Rb pathway is
      often inactivated in human tumors, resulting in deregulated-E2F activity that
      promotes proliferation or cell death, depending on the cellular context.
      Specifically, the outcome of deregulated-E2F activity is determined by
      integration of signals coming from the cellular DNA and the external environment.
      Alterations in cell proliferation and cell-death pathways are key features of
      transformed cells and, therefore, an understanding of the variables that
      determine the outcome of E2F activation is pivotal for cancer research and
      treatment. In this review, we discuss recent studies that have elucidated some of
      the signals affecting E2F activity and that have revealed additional E2F targets
      and functions, thereby enriching the understanding of this versatile
      transcription-factor family.

PMID- 18805010
TI  - The ups and downs of SIRT1.
AB  - Reversible acetylation has emerged as a key post-translational modification of
      proteins. Although the number of acetylated proteins is rapidly growing, the ways
      in which protein acetyltransferases and deacetylases connect with extracellular
      stimuli remain unclear. Recently, a regulatory network has emerged that controls
      the expression and activity of SIRT1, a mammalian class-III protein deacetylase.
      SIRT1 is an important regulator of metabolism, senescence, cancer and, possibly,
      longevity and is connected with crucial stress-responsive signal-transduction
      pathways. These connections provide important clues about how protein acetylation
      and deacetylation mediate cellular adaptations to extrinsic stress.

PMID- 18805011
TI  - Fluorescent polycyclic ligands for nitric oxide synthase (NOS) inhibition.
AB  - In recent years polycyclic compounds have been shown to exhibit pharmacological
      profiles of importance in the symptomatic and proposed curative treatment of
      neurodegenerative diseases (e.g., Parkinson's and Alzheimer's disease). These
      structures also show modification and improvement of the pharmacokinetic and
      pharmacodynamic properties of drugs in current use. Nitric oxide (NO) is a
      molecular messenger involved in a number of physiological processes in mammals.
      It is synthesised by nitric oxide synthase (NOS) from L-arginine and its
      overproduction could lead to a number of neurological disorders. The aim of this
      study was to synthesise a series of novel indazole, indole and other fluorescent
      derivatives conjugated to polycyclic structures for evaluation in NOS assays. NOS
      is a target system where fluorescent techniques and fluorescently labelled NOS
      inhibitors can be used for detecting the biophysical properties of enzyme-ligand
      interactions and thus facilitate development of novel inhibitors of
      neurodegeneration. This could lead to a greater insight into the neuroprotective
      mechanism and a possible cure/treatment for neurodegenerative diseases. A series
      of compounds incorporating polycyclic structures such as 3-hydroxy-4-aza-8
      oxoheptacyclo[9.4.1.0.(2,10)0.(3,14)0.(4,9)0.(9,13)0(12,15)]tetradecane and
      amantadine as well as suitable fluorescent moieties were selected for synthesis.
      In the biological evaluation the oxyhaemoglobin (oxyHb) assay was employed to
      determine the activity of the novel compounds at an enzymatic level of NOS.
      IC(50) values of the novel fluorescent compounds were compared to that of
      aminoguanidine (AG) and 7-nitroindazole (7-NI), two known NOS inhibitors, and
      showed moderate to high affinity (IC(50) values ranging from 7.73 microM to 0.291
      microM) for the NOS enzyme.

PMID- 18805012
TI  - Synthesis and biological evaluation of polymethoxylated 4-heteroarylcoumarins as
      tubulin assembly inhibitor.
AB  - A series of syn-restricted polymethoxylated 4-heteroarylcoumarins--the
      isostuctural analogs of combretastatin A-4--was synthesized by Suzuki-Miyaura
      cross-coupling reaction and evaluated for antiproliferative activity. The 4-(1
      methyl-1H-indol-5-yl)chromen-2-ones exhibit a potent cytotoxicity against HBL100
      epithelial cell line with an IC(50) value amounting to 0.098 and 0.078 microM,
      respectively. The two compounds, having an indolyl moiety, potent inhibit in
      vitro microtubule assembly with a substoichiometric mode of action. A structure
      activity relationship was discussed and the indolyl moiety was proved to be a
      good surrogate for the 3-hydroxy-4-methoxyphenyl ring of CA-4.

PMID- 18805013
TI  - Design, synthesis and evaluation of D-galactose-beta-cyclodextrin conjugates as
      drug-carrying molecules.
AB  - Several kinds of D-galactose-beta-cyclodextrin conjugates having a phenyl group
      in the spacers between the D-galactose and beta-cyclodextrin were designed and
      synthesized as drug-carrying molecules. Their evaluation as drug-carrying
      molecules was done by measuring the molecular interactions with the anticancer
      agent, doxorubicin, and with the d-galactose-binding peanut lectin using an SPR
      optical biosensor. The SPR analyses showed that these conjugates had remarkably
      high inclusion associations of 10(5) approximately 10(7)M(-1) levels for the
      immobilized doxorubicin. Their association constants for immobilized peanut
      lectin were at the level of 10(4) approximately 10(5)M(-1), as we expected. These
      conjugates will be useful drug-carrying models which can site-specifically carry
      doxorubicin to the cells containing D-galactose-binding lectin.

PMID- 18805014
TI  - X-ray diffraction imaging--a multi-generational perspective.
AB  - A brief description is given of some applications of X-ray diffraction imaging
      (XDI) in security screening, including detection of narcotics and a wide range of
      explosives: organic (plastic) explosives, liquids, home-made explosives (HMEs)
      and special nuclear materials (SNMs). A Bayesian formulation of the "rare event
      scenario" is presented, allowing the probability to be quantified that an
      unlikely threat is indeed present when an uncertain detection system raises an
      alarm. Granted the utility of X-ray diffraction (XRD) as a significant screening
      modality for false-alarm resolution, the topic of its technological feasibility
      is addressed. It is shown that, in analogy to computed tomography, XDI permits a
      significant reduction to be achieved in measurement time per object volume
      element (voxel) compared with that of a classical X-ray diffractometer. This
      reduction can be accomplished by designing the XDI system to record energy
      dispersive XRD profiles from many volume elements (object voxels) in parallel. A
      general scheme for designing "massively-parallel" (MP) XDI systems is presented.
      XDI configurations of the first generation (1 voxels(-1)), second generation (100
      voxelss(-1)) and third generation (10(4) voxelss(-1)) are presented and
      discussed. Three alternative 3rd Generation XDI geometries, namely: direct fan
      beam; parallel (waterfall) beam; and inverse fan-beam are compared with respect
      to technological realization. Directions for future development of XDI in
      screening applications are outlined.

PMID- 18805015
TI  - Neutron- and photon-activation detection limits in breast milk analysis for
      prospective dose evaluation of the suckling infant.
AB  - Complex situations related to the environment, as in the regions affected by the
      Chernobyl accident and regions in which nuclear weapons testing were undertaken,
      as in Semipalatinsk, could be reflected in the trace element content in mothers'
      milk. The evaluation of fractional transfer to milk of ingested or inhaled
      activity and of the corresponding dose coefficients for the infant, following a
      mothers' radioactive intake, can take advantage from wide-ranging studies of
      elemental and radionuclide contents in mothers' milk. In this work the
      possibility to determine elements, such as Ru, Zr, Nb, Te, Ce, Th, U, in milk
      powder has been investigated. Although results from elemental analyses of breast
      milk are to be found in the literature, the determination of the identified
      elements has attracted poor attention since they are not considered essential
      elements from a biological point of view. Nevertheless, in the case of
      radioactive releases to the environment, such data could be of interest in
      evaluation of dose to the breast-fed infant.

PMID- 18805016
TI  - Uranium disequilibrium as a hydrological aid in studying the salinization
      processes in the Southeastern Coastal Plain of Israel.
AB  - Saline waters, of unknown origin, have been encountered in the basal portions of
      the phreatic Coastal Plain aquifer of Israel. (234)U/(238)U disequilibrium was
      used to trace their origin to the evaporate layers within the Saqiye aquiclude,
      the most saline, and the warmest (up to 42 degrees C) waters are also those that
      have the highest uranium concentrations combined with low (234)U/(238)U activity
      ratios, derived as the ascending brines traverse underlying uranium-rich Senonian
      phosphorites, in secular equilibrium along fault conduits.

PMID- 18805017
TI  - Evaluation of 133Xe and 133Xe(m) decay data.
AB  - This paper presents the decay data evaluation of (133)Xe and (133)Xe(m), which
      includes the most recent available data, such as half-life results and gamma-ray
      intensities that have not been considered in previous evaluations. The adopted
      internal conversion coefficients (ICC) have been calculated using the 'Frozen
      Orbital' approximation and are compared here to recent measured values. Recent Q
      value tabulations, recommended gamma-ray energies for calibrations, as well as
      new evaluated gamma-ray intensities for the 81- and 233-keV lines (37.0 (3)% and
      10.16 (13)%, respectively) are also presented in this evaluation. Atomic
      radiation emission probabilities (X-ray and Auger electron) associated with
      nuclear radiations have been deduced and also included in this work.

PMID- 18805018
TI  - Heterotopic parathyroid gland tissue in the parotid gland adjacent to a
      pleomorphic adenoma.

PMID- 18805019
TI  - Current management of stage I testicular non-seminomatous germ cell tumours.
AB  - Testicular germ cell tumors represent the most common malignancies in young males
      between the ages of 15 and 35; 50% of those with non-seminomatous germ cell
      tumors (NSGCT) have clinical stage I at diagnosis. Predictors for relapse include
      lymphovascular invasion, percentage of embryonal-cell carcinoma component,
      absence of yolk-sack histology and MIB1 proliferation rate. Therapeutic options
      following orchidectomy in stage I NSGCT comprise nerve-sparing retroperitoneal
      lymph node dissection (RPLND), surveillance or adjuvant cisplatin-based
      chemotherapy. Using a risk adapted approach, in about 50% of patients with
      clinical stage I NSGCT surveillance is favored in patients with good compliance.
      Adjuvant chemotherapy is recommended for patients at high risk for developing
      metastatic disease. Non-seminomatous germ cell testicular cancer is a curable
      neoplasia. All available treatment modalities produce excellent results, with a
      long-term survival of almost 100%. Consequently, therapy-induced toxicity is an
      important concern in the management of these patients. An individually tailored
      approach that takes into account the prognostic factor profile, as well as the
      patients' preferences and their ability to comply with treatment, is the key for
      the successful management of stage I testicular cancer.

PMID- 18805020
TI  - Anti-Mullerian hormone and ovarian dysfunction.
AB  - Anti-Mullerian hormone (AMH) has important roles in postnatal ovarian function.
      Produced by ovarian granulosa cells, AMH is involved in initial follicle
      development. In fact, serum AMH level correlates with ovarian follicle number. In
      patients with polycystic ovary syndrome (PCOS), AMH levels are elevated, which
      indicates its potential relevance in PCOS diagnosis and management. AMH
      represents a useful clinical marker for the assessment of ovarian reserve in
      cases of subfertility caused by advanced age in women. A potential role for AMH
      in dominant follicle selection has also been suggested. Future challenges
      comprise the availability of a well-standardized assay and the development of AMH
      agonists and antagonists as possible tools to manipulate ovarian function for
      contraception or ovarian longevity.

PMID- 18805021
TI  - A synergistic role for IL-1beta and TNFalpha in monocyte-derived IFNgamma
      inducing activity.
AB  - Although much is known about classic IFNgamma inducers, little is known about the
      IFNgamma inducing capability of inflammasome-activated monocytes. In this study,
      supernatants from LPS/ATP-stimulated human monocytes were analyzed for their
      ability to induce IFNgamma production by KG-1 cells. Unexpectedly, monocyte
      derived IFN inducing activity was detected, but it was completely inhibited by IL
      1beta, not IL-18 blockade. Moreover, size-fractionation of the monocyte
      conditioned media dramatically reduced the IFNgamma inducing activity of IL
      1beta, suggesting that IL-1beta requires a cofactor to induce IFNgamma production
      in KG-1 cells. Because TNFalpha is known to synergize with IL-1beta for various
      gene products, it was studied as the putative IL-1beta synergizing factor.
      Although recombinant TNFalpha (rTNFalpha) alone had no IFNgamma inducing
      activity, neutralization of TNFalpha in the monocyte conditioned media inhibited
      the IFNgamma inducing activity. Furthermore, rTNFalpha restored the IFNgamma
      inducing activity of the size-fractionated IL-1beta. Finally, rTNFalpha
      synergized with rIL-1beta, as well as with rIL-1alpha and rIL-18, for KG-1
      IFNgamma release. These studies demonstrate a synergistic role between TNFalpha
      and IL-1 family members in the induction of IFNgamma production and give caution
      to interpretations of KG-1 functional assays designed to detect functional IL-18.

PMID- 18805022
TI  - Optimization of the formulation for a candidate lyophilised tetanus toxoid
      reference preparation.
AB  - Tetanus toxoid is a vital primary reference material used for standardization of
      assays required to establish the antigenic purity of tetanus toxoid for vaccine
      production. Several formulations were assessed and ampouled fills of each
      formulation lyophilised. The relative Lf content determined by Ramon
      flocculation, SRD, and ELISA assays was measured. The stability of the tetanus
      toxoid activity in each formulation was assessed by accelerated degradation
      studies. Formulations containing glycine were not suitable in flocculation tests
      but both sorbitol and trehalose formulations were. The trehalose/sodium chloride
      formulation had a good appearance, showed good activity in all assays and
      maintained its activity best under stress conditions. This formulation has been
      applied to a large scale batch of ampoules prepared as a WHO candidate
      replacement standard, evaluated in a collaborative study and accepted as a
      replacement WHO IS for use in flocculation test (WHO ECBS, October 2007, ref no
      BS/07.2061). The stability of this formulation was also excellent for the large
      scale batch. The benefits of using thermal analysis and freeze drying microscopy
      coupled with small scale lyophilisation trials in order to screen formulations
      for the preparation of batches of biological reference materials are
      demonstrated.

PMID- 18805023
TI  - Do judgments about freedom and responsibility depend on who you are? Personality
      differences in intuitions about compatibilism and incompatibilism.
AB  - Recently, there has been an increased interest in folk intuitions about freedom
      and moral responsibility from both philosophers and psychologists. We aim to
      extend our understanding of folk intuitions about freedom and moral
      responsibility using an individual differences approach. Building off previous
      research suggesting that there are systematic differences in folks'
      philosophically relevant intuitions, we present new data indicating that the
      personality trait extraversion predicts, to a significant extent, those who have
      compatibilist versus incompatibilist intuitions. We argue that identifying groups
      of people who have specific and diverse intuitions about freedom and moral
      responsibility offers the possibility for theoretical advancement in philosophy
      and psychology, and may in part explain why some perennial philosophical debates
      have proven intractable.

PMID- 18805024
TI  - Nonunion of the clavicle treated with plate fixation: a review of forty-seven
      consecutive cases.
AB  - Forty-seven consecutive patients underwent superior plating for clavicular
      nonunion between 1995 and 2005. This retrospective analysis was performed to
      assess the efficacy of plate fixation and the need for iliac crest bone grafting.
      Forty-three patients were treated with pelvic reconstruction plates and four with
      straight dynamic compression plates. Of the patients, 30 were treated with local
      bone graft only, 14 with demineralized bone matrix, and 3 with distant autogenous
      bone graft. Of the fractures, 93% united after a single operation. Of the
      patients, 69% returned the Disabilities of the Arm, Shoulder and Hand
      questionnaire. The mean Disabilities of the Arm, Shoulder and Hand score was 14.6
      (range, 0-53). Plate prominence or sensitivity resulted in removal in 20% of
      cases. We believe that superiorly applied plate fixation is effective for the
      treatment of clavicular nonunion. Distant autogenous bone graft is not necessary
      in most cases to obtain union.

PMID- 18805025
TI  - Memory outcome 2 years after anterior temporal lobectomy in patients with drug
      resistant epilepsy.
AB  - PURPOSE: Memory decline is often observed after anterior temporal lobectomy
      (ATL), particularly in patients with dominant hemisphere resections. However, the
      follow-up length has been 1 year or less in most studies. Our aims were to
      examine postoperative memory changes over a longer period and to identify
      baseline demographic and clinical predictors of memory outcome. METHODS: We
      administered material-specific memory tests at baseline, and 1 and 2 years after
      surgery to 82 consecutive right-handed patients (52% males) who underwent ATL for
      drug-resistant temporal lobe epilepsy (TLE) (35 left, 47 right) after a non
      invasive presurgical protocol. Repeated measures multivariate analysis of
      variance (RM-MANOVA) was used to examine the relationship between changes in
      memory tests scores over time and side of TLE and pathology. Also, standardized
      residual change scores were calculated for each memory test and entered in
      multiple linear regression models aimed at identifying baseline predictors of
      better memory outcome. RESULTS: RM-MANOVA revealed a significant change in memory
      test scores over time, with an interaction between time and side of surgery, as 2
      years after surgery patients with RTLE were improved while patients with LTLE
      were not worse as compared with baseline. Pathology was not associated with
      changes in memory scores. In multiple regression analysis, significant
      associations were found between right TLE and greater improvement in verbal
      memory, younger age and greater improvement in visuospatial memory, and male
      gender and greater improvement in both verbal and visuospatial memory.
      CONCLUSIONS: Our results suggest that the long-term memory outcome of TLE
      patients undergoing ATL without invasive presurgical assessment may be good in
      most cases not only for right-sided but also for left-sided resections.

PMID- 18805026
TI  - Evaluation of a Photographic Chondropathy Score (PCS) for pathological samples in
      a study of inflammation in tibiofemoral osteoarthritis.
AB  - OBJECTIVE: Severity of structural change in knee osteoarthritis (OA) can be
      measured radiologically, macroscopically or microscopically. Existing methods
      have limitations for use in laboratory studies. We have developed a Photographic
      Chondropathy Score (PCS) for use with pathological samples. We have compared the
      ability of the different severity measures to distinguish between samples
      obtained at total knee replacement surgery or postmortem (PM), and to detect
      associations between structural severity and synovitis. METHOD: Tibial plateaux
      and femoral condyles were collected from 84 patients undergoing surgery or PM.
      Each sample was photographed and scored. Limits of agreement and repeatability
      coefficients were calculated for PCS. Scores for radiological joint space
      narrowing (JSN) and osteophytes, histological cartilage changes (Mankin), and
      synovitis were assigned. Data were analysed using Mann-Whitney U tests,
      Spearman's correlation coefficient or logistic regression. RESULTS: A total of
      116 knees were analysed from 84 patients. Both medial tibial plateaux and total
      joint PCS showed good repeatability, internal consistency and reliability between
      observers. PCS, radiographic and Mankin's scores were all modestly positively
      correlated (r values 0.28-0.55). PCS and Mankin scores were greater in surgical
      than PM samples. Synovial inflammation was associated with higher PCS and
      radiological JSN scores (r values 0.43-0.48), irrespective of diagnosis.
      CONCLUSION: Macroscopic, microscopic and radiographical severity scores are
      complementary measures of structural severity in knee OA. Synovial inflammation
      was associated with increased OA structural severity, suggesting a possible role
      of chronic synovitis in cartilage damage.

PMID- 18805027
TI  - Analysis of radial variations in material properties and matrix composition of
      chondrocyte-seeded agarose hydrogel constructs.
AB  - OBJECTIVE: To examine the radial variations in engineered cartilage that may
      result due to radial fluid flow during dynamic compressive loading. This was done
      by evaluating the annuli and the central cores of the constructs separately.
      METHOD: Chondrocyte-seeded agarose hydrogels were grown in free-swelling and
      dynamic, unconfined loading cultures for 42 days. After mechanical testing,
      constructs were allowed to recover for 1-2h, the central 3mm cores removed, and
      the cores and annuli were retested separately. Histological and/or biochemical
      analyses for DNA, glycosaminoglycan (GAG), collagen, type I collagen, type II
      collagen, and elastin were performed. Multiple regression analysis was used to
      determine the correlation between the biochemical and material properties of the
      constructs. RESULTS: The cores and annuli of chondrocyte-seeded constructs did
      not exhibit significant differences in material properties and GAG content.
      Annuli possessed greater DNA and collagen content over time in culture than
      cores. Dynamic loading enhanced the material properties and GAG content of cores,
      annuli, and whole constructs relative to free-swelling controls, but it did not
      alter the radial variations compared to free-swelling culture. CONCLUSION:
      Surprisingly, the benefits of dynamic loading on tissue properties extended
      through the entire construct and did not result in radial variations as measured
      via the coring technique in this study. Nutrient transport limitations and the
      formation of a fibrous capsule on the periphery may explain the differences in
      DNA and collagen between cores and annuli. No differences in GAG distribution may
      be due to sufficient chemical signals and building blocks for GAG synthesis
      throughout the constructs.

PMID- 18805028
TI  - Outcomes of endovascular repair of acute thoracic aortic injury: interrogation of
      the New Zealand thoracic aortic stent database (NZ TAS).
AB  - OBJECTIVES: Report the New Zealand national experience of endovascular repair of
      acute traumatic thoracic aortic injuries (TTAIs). DESIGN: Retrospective analysis
      of the New Zealand thoracic aortic stent database between December 2001 and
      December 2007. MATERIALS AND METHODS: Of the 134 patients on the database, 27
      patients (20%) underwent endovascular repair of TTAI. Data collected included
      age, sex, cause of injury, details of the procedure, complications and mortality.
      RESULTS: Most patients were young, median age 20 (15-78), male (n=19, 70%), and
      involved in motor vehicle accidents (n=23, 85%). Median length of aorta stented
      was 117 mm (77-200 mm). Great vessel origins were covered intentionally in 23
      (85%) patients, four (17%) requiring a hybrid procedure. Average procedure time
      was 98.3 min (35-180). Primary technical success was 96%, secondary technical
      success 100%. Endoleaks were observed in four (15%) patients, one requiring a
      second endovascular procedure. There were no conversions to open surgery.
      Procedure-related complications occurred in four (15%) patients. No patient
      developed cord injury. All cause mortality at 30 days is one (4%) and at
      discharge is two (7%) due to associated poly-trauma. CONCLUSION: Our results add
      further evidence of the safety of endovascular repair of thoracic aortic injury
      and compare favourably with those of other centres.

PMID- 18805029
TI  - Serological and molecular evidence of hepatitis E virus in swine in Brazil.
AB  - Active hepatitis E virus (HEV) infections in two Brazilian swine herds were
      investigated. In study 1, 26 piglets born to five anti-HEV positive sows were
      monitored from birth to post-partum week 22. Serum samples were screened for the
      detection of anti-HEV antibodies and a nested RT-PCR used to examine the HEV
      genome. Passive transfer of immunity was confirmed. At week 22, 23/26 (88.4%) of
      the piglets had seroconverted. Genome amplification was achieved in a feces pool
      from one holding pen and in one serum sample, both from 13-week-old animals.
      Histology was suggestive of a potential HEV infection. In the second study, 47
      piglets born to six anti-HEV-positive sows were monitored after weaning.
      Seroconversion was determined in eight animals at 6-8 weeks of age. HEV RNA was
      detected in two pools from a holding pen for 12-16-week-old animals. Brazilian
      isolates were classified as genotype 3. This is the first molecular evidence of
      HEV infection in Brazilian pig herds.

PMID- 18805030
TI  - Equine herpesvirus-1 myeloencephalopathy: a review of recent developments.
AB  - Equine herpes myeloencephalopathy (EHM), although a relatively uncommon
      manifestation of equine herpesvirus-1 (EHV-1) infection, can cause devastating
      losses on individual farms or boarding stables. Although outbreaks of EHM have
      been recognized for centuries in domestic horse populations, many aspects of this
      disease remained poorly characterized. In recent years, an improved understanding
      of EHM has emerged from experimental studies and from data collected during field
      outbreaks at riding schools, racetracks and veterinary hospitals throughout North
      America and Europe. These outbreaks have highlighted the contagious nature of EHV
      1 and have prompted a re-evaluation of diagnostic procedures, treatment
      modalities, preventative measures and biosecurity protocols for the disease. This
      review concentrates on these and other selected, clinically relevant aspects of
      EHM.

PMID- 18805031
TI  - The tail pigmentation pattern of C57BL/6J mice affects nociception/pain
      quantification in the tail flick test.
AB  - The heat radiant tail flick test is commonly used to quantify nociception and
      pain levels. Likewise, the C57BL/6J strain of mice is frequently used in pain
      related studies as transgenic mice are often backcrossed onto this background.
      C57BL/6J mice naturally develop non-pigmented patches of variable length on the
      distal part of the tail that could conceivably modify the response latency in
      tail flick assays. Here we find that these non-pigmented regions, in a position
      independent manner, significantly increase the response latency in the heat
      radiant tail flick assay, but not the warm water immersion test. This finding
      demonstrates that the extent of pigmentation, and not other potential variables
      between pigmented and non-pigmented skin, affects radiant heat tail flick
      latency, and should be considered in the design of pain-related studies using
      mice with variable tail pigmentation.

PMID- 18805032
TI  - Molecular basis of agonicity and antagonicity in the androgen receptor studied by
      molecular dynamics simulations.
AB  - Treatment of prostate cancer patients with antiandrogens is initially successful,
      though the therapy often becomes refractory over the time. This mechanism is not
      fully understood, but the presence of androgen receptor (AR) mutant forms which
      are activated by antiandrogens and other endogenous ligands, and overexpression
      of the receptor have been suggested. In an attempt to explain the molecular basis
      for agonicity and antagonicity in the androgen receptor, and the changes on
      biological activity of subtle modifications at the ligand and receptor
      (mutations) level, molecular dynamics simulations were performed on the androgen
      receptor wild type (WT), and T877A and W741 mutant forms, complexed with several
      non-steroidal androgens. The stabilizing role of residues from helices 3, 5, 11
      and 12 was observed in non-steroidal androgens R-3, S-1, and R-bicalutamide and
      hydroxyflutamide in resistant mutations. In the AR WT antiandrogen R-bicalutamide
      complex, destabilization of M895 by both W741 and the sulfonyl linkage of the
      ligand may be responsible for reported antagonism. Changes in the ligand or
      mutations alleviating this effect were observed to stabilize the receptor in the
      active conformation, thus developing resistance to R-bicalutamide. The results
      presented provide a plausible explanation for the molecular basis of agonicity
      and antagonicity in the androgen receptor, and complement previous studies using
      static crystal structures, incorporating for the first time protein dynamics into
      the analysis. Thus, our results provide a valuable framework for the structure
      based design of improved antiandrogens.

PMID- 18805033
TI  - Adherence to, and results of, physical therapy programs in patients with hip or
      knee osteoarthritis. Development of French clinical practice guidelines.
AB  - OBJECTIVE: To develop recommendations regarding adherence to physical therapy
      programs by patients with hip or knee osteoarthritis. METHODS: We used the method
      recommended by the French Society for Physical and Rehabilitation Therapy
      (SOFMER), which combines a systematic literature review, a practice survey, and
      validation by a multidisciplinary panel of experts. RESULTS: When setting up
      exercise programs for patients with lower limb osteoarthritis, measures should be
      taken to increase effectiveness by optimizing adherence. Patient selection is
      among these measures, as exercise programs are more likely to succeed in patients
      with a history of being physically active, a positive view of the suggested
      program, and/or favorable social and material conditions. Regardless of the type
      of exercise, the program should be tailored to exercise capacity and pain level
      (professional consensus). Patient adherence can be improved by explaining the
      expected results to the patient, asking the patient to keep a self-evaluation
      diary, conducting long-term evaluations (by phone or mail), and providing follow
      up visits. CONCLUSION: Studies of adherence according to the type of exercise are
      needed. The relevance of widely used incentives in patients with hip or knee
      osteoarthritis should be evaluated in new therapeutic trials.

PMID- 18805034
TI  - Efficacy of rituximab in Felty's syndrome.

PMID- 18805035
TI  - [Environmental endocrine disruptors and breast cancer: new risk factors?].
AB  - Human epidemiological studies and experimental animal data strongly suggest that
      xenobiotics with estrogenic activity may participate in to the increasing
      incidence of breast cancer, the most frequent cancer all around the world.
      Several reports have since 15 years reported positive correlations between blood
      or peritumoral adipose tissue levels of persistent organic compounds including
      organochloride pesticides and breast cancer risk. Moreover, fetal or perinatal
      exposition to low doses of such endocrine disruptors induce premalignant or
      malignant transformation of adult mammary gland in rodents. However, this
      environmental endocrine disrupter hypothesis still needs to be demonstrated.
      Further human studies are needed which will consider the exposition window, the
      association of several xenoestrogens, the molecular mechanisms involved and the
      possible individual genetic susceptibility in order to identify pertinent
      biomarkers and to define acceptable environmental concentration levels for
      agricultural or industrial chemical new products to be used.

PMID- 18805036
TI  - FEM simulation of a sono-reactor accounting for vibrations of the boundaries.
AB  - The chemical effects of acoustic cavitation are obtained in sono-reactors built
      up from a vessel and an ultrasonic source. In this paper, simulations of an
      existing sono-reactor are carried out, using a linear acoustics model, accounting
      for the vibrations of the solid walls. The available frequency range of the
      generator (19-21 kHz) is systematically scanned. Global quantities are plotted as
      a function of frequency in order to obtain response curves, exhibiting several
      resonance peaks. In absence of the precise knowledge of the bubbles size
      distribution and spatial location, the attenuation coefficient of the wave is
      taken as a variable, but spatially uniform parameter, and its influence is
      studied. The concepts of acoustic energy, intensity, active power, and source
      impedance are recalled, along with the general balance equation for acoustic
      energy, which is used as a convergence check of the simulations. It is shown that
      the interface between the liquid and the solid walls cannot be correctly
      represented by the simple approximations of either infinitely soft, or infinitely
      hard boundaries. Moreover, the liquid-solid coupling allows the cooling jacket to
      receive a noticeable part of the input power, although it is not in direct
      contact with the sonotrode. It may therefore undergo cavitation and this feature
      opens the perspective to design sono-reactors which avoid direct contact between
      the working liquid and the sonotrode. Besides, the possibility to shift the main
      pressure antinode far from the sonotrode area by exciting a resonance of the
      system is examined.

PMID- 18805037
TI  - Differences in skin sympathetic involvements between two chronic autonomic
      disorders: multiple system atrophy and pure autonomic failure.
AB  - OBJECTIVE: Certain stimuli evoke increased sweat secretion (sympathetic sweat
      response; SSwR) and reduced skin blood flow (skin vasomotor reflex; SkVR) in the
      palm/sole. We evaluated SSwR and SkVR in patients with multiple system atrophy
      (MSA) and pure autonomic failure (PAF). METHODS: SSwR and SkVR on the palm in
      response to deep inspiration and mental arithmetic were recorded in 11 MSA
      patients, 11 PAF patients, and 11 healthy controls. In addition, the head-up tilt
      test was performed, and the coefficient of variation of R-R intervals (CV(R-R))
      was obtained. RESULTS: SSwR amplitudes were significantly lower in the MSA and
      PAF patients than the controls. SkVR amplitudes in the PAF patients were
      significantly lower than the controls, but preserved in the MSA patients. In head
      up tilt tests, all MSA and PAF patients showed orthostatic hypotension, with
      similar severity. CV(R-R) was low in the MSA and PAF patients, but a significant
      difference was found only between the PAF and control groups. CONCLUSION: In the
      MSA patients, SkVR was preserved, but SSwR was diminished. In the PAF patients,
      both SkVR and SSwR were attenuated. The combination of SkVR and SSwR tests may
      differentiate MSA and PAF.

PMID- 18805038
TI  - Biomechanical analysis of axial distraction mobilization of the glenohumeral
      joint--a cadaver study.
AB  - The axial distraction mobilization techniques are frequently employed for
      treating patients with joint hypomobility. However, there is a lack of basic
      biomechanical studies and description of this procedure. The purpose of this
      study was to analyze humeral head displacement while performing an axial
      distraction mobilization of the glenohumeral joint. Twelve experienced orthopedic
      physical therapists participated. Distraction mobilization techniques were
      performed in three different positions of glenohumeral abduction on a fresh
      cadaveric specimen. Outcome measures were displacements of the humeral head
      center during distraction mobilization. Result indicated that displacement of the
      humeral head was largest in the resting position (27.38 mm) followed by the
      neutral (22.01 mm) and the end range position (9.34 mm). There were significant
      differences for both the displacement of the humeral head (p<0.002) and the
      distraction forces used (p<0.015) among the three joint positions. Greater gain
      in mobility was obtained in distraction at the end range position. In conclusion,
      during distraction mobilization, the force applied by the therapist and
      displacement of the humeral head depends on the joint position tested. Our
      results also provide rationales for choosing end range distraction mobilization
      for improving joint mobility.

PMID- 18805039
TI  - Benefits of multisensory learning.
AB  - Studies of learning, and in particular perceptual learning, have focused on
      learning of stimuli consisting of a single sensory modality. However, our
      experience in the world involves constant multisensory stimulation. For instance,
      visual and auditory information are integrated in performing many tasks that
      involve localizing and tracking moving objects. Therefore, it is likely that the
      human brain has evolved to develop, learn and operate optimally in multisensory
      environments. We suggest that training protocols that employ unisensory stimulus
      regimes do not engage multisensory learning mechanisms and, therefore, might not
      be optimal for learning. However, multisensory-training protocols can better
      approximate natural settings and are more effective for learning.

PMID- 18805040
TI  - Development of the self-concept during adolescence.
AB  - Adolescence is a period of life in which the sense of 'self' changes profoundly.
      Here, we review recent behavioural and neuroimaging studies on adolescent
      development of the self-concept. These studies have shown that adolescence is an
      important developmental period for the self and its supporting neural structures.
      Recent neuroimaging research has demonstrated that activity in brain regions
      associated with self-processing, including the medial prefrontal cortex, changes
      between early adolescence and adulthood. These studies indicate that
      neurocognitive development might contribute to behavioural phenomena
      characteristic of adolescence, such as heightened self-consciousness and
      susceptibility to peer influence. We attempt to integrate this recent
      neurocognitive research on adolescence with findings from developmental and
      social psychology.

PMID- 18805041
TI  - Taking a new look at looking at nothing.
AB  - A crucial question in cognitive science is how linguistic and visual information
      are integrated. Previous research has shown that eye movements to objects in the
      visual environment are locked to linguistic input. More surprisingly, listeners
      fixate on now-empty regions that had previously been occupied by relevant
      objects. This 'looking at nothing' phenomenon has been linked to the claim that
      the visual system constructs sparse representations of the external world and
      relies on saccades and fixations to extract information in a just-in-time manner.
      Our model provides a different explanation: based on recent work in visual
      cognition and memory, it assumes that the visual system creates and stores
      detailed internal memory representations, and that looking at nothing facilitates
      retrieval of those representations.

PMID- 18805042
TI  - The pathophysiology of ocular allergy: a review.
AB  - Allergic eye disease is an abnormal immune hypersensitivity response to
      allergens. It is characterized by IgE-mediated and/or T-lymphocyte-mediated
      immune hypersensitivity reactions that lead to an immune response, resulting in
      the clinical manifestations of ocular allergy. This review will focus on
      immunopathophysiology of the different types of allergic eye disease commonly
      encountered in the primary care setting. The objective is to provide the
      clinician with a considerable understanding of the immunopathogenesis of allergic
      eye disease. The primary focus of this review will be on the antibody- and cell
      mediated immune hypersensitivity reactions relevant to allergic eye disease, the
      different phases of ocular allergic immune response and the histopathological
      manifestations of these commonly encountered ocular allergies. The basic concepts
      of immunology with emphasis on adaptive immunity and lymphocyte activation, as
      well as the components of the immune system that are relevant to ocular allergy
      will also be reviewed.

PMID- 18805043
TI  - DNA ploidy analysis by image cytometry helps to identify oral epithelial
      dysplasias with a high risk of malignant progression.
AB  - Abnormal DNA content (aneuploidy) has been associated with malignant and
      premalignant epithelial lesions. The presence of aneuploidy in tumours at an
      early stage and in dysplastic lesions suggests that analysis of DNA content may
      be a useful marker for determination of prognosis in these lesions. The aim of
      this study was to use DNA image cytometry to evaluate aneuploidy in oral
      dysplastic lesions and to determine whether aneuploidy is associated with
      malignant progression. Forty-two lesions of oral epithelial dysplasias (OED) that
      had progressed to oral squamous cell carcinoma (OSCC) and 44 lesions that did not
      progress were analysed for DNA ploidy using image cytometry of nuclear monolayers
      prepared from paraffin-embedded tissue. Forty-two OSCC that had arisen from the
      OED cases and five samples of normal oral mucosa samples (NOM) were also
      examined. Aneuploidy was found in 14/42 (33.3%) of the OED that progressed, but
      in only 5/44 (11.3%) of OED that did not progress (p=0.01). A total of 19 OED
      were aneuploid of which 74% showed malignant progression compared to only 42% of
      the diploid lesions. The sensitivity and specificity of DNA image cytometry to
      detect cases with high risk of malignant progression was 0.33 and 0.88,
      respectively. The PPV and NPV were 0.74 and 0.58. We conclude that aneuploid oral
      dysplastic lesions have a high risk of malignant progression and that DNA image
      cytometry might help to identify those lesions most at risk.

PMID- 18805045
TI  - Sulforaphane enhances caspase-dependent apoptosis through inhibition of
      cyclooxygenase-2 expression in human oral squamous carcinoma cells and nude mouse
      xenograft model.
AB  - In this study, we found that oral squamous cell carcinomas (OSCCs) in Korean
      patients have a high level of COX-2 expression when compared with normal mucosa.
      Sulforaphane (SFN), rich in cruciferous vegetables, has been reported to display
      anti-cancer activity against many cancers. However, the effect and molecular
      mechanism of SFN in the proliferation of OSCC still remains unclear. To elucidate
      this mechanism, we investigated the anti-proliferative effect of SFN on KB and YD
      10B cells and demonstrated that SFN significantly induced caspase-dependent
      apoptosis. Also, we observed that SFN inhibited COX-2 but not COX-1. In addition,
      bcl-2 protein, one of downstream targets of COX-2, was down-regulated by SFN.
      Furthermore, SFN also inhibited tumor growth in KB cell xenografts. These results
      show that SFN can act as a potent anti-oral cancer compound by inhibiting COX-2
      activity.

PMID- 18805046
TI  - Expression of growth differentiation factor 15 is positively correlated with
      histopathological malignant grade and in vitro cell proliferation in oral
      squamous cell carcinoma.
AB  - Previously, we established an in vitro cellular carcinogenesis model of oral
      squamous cell carcinoma (OSCC) and expression microarray analysis showed that the
      gene encoding growth differentiation factor 15 (GDF15) was significantly
      upregulated in this model. In this study, we confirmed that expression of GDF15
      was increased both at mRNA and protein levels in a panel of OSCC lines and
      clinical samples from primary OSCC patients. We also observed that expression of
      GDF15 was positively correlated with the malignancy of the disease: a higher
      level of GDF15 expression indicates a higher malignant grade of OSCC. Treatment
      of OSCC cell line (Tca3118) with siRNA against GDF15 significantly inhibited
      cellular proliferation and colony formation. Based on these observations, we
      conclude that GDF15 is a positive gene of OSCC development and progression and
      GDF15 can be used as an additional marker for histopathologic evaluation of OSCC
      differentiation.

PMID- 18805044
TI  - Dysregulated molecular networks in head and neck carcinogenesis.
AB  - Multiple genetic and epigenetic events, including the aberrant expression and
      function of molecules regulating cell signaling, growth, survival, motility,
      angiogenesis, and cell cycle control, underlie the progressive acquisition of a
      malignant phenotype in squamous carcinomas of the head and neck (HNSCC). In this
      regard, there has been a recent explosion in our understanding on how
      extracellular components, cell surface molecules, and a myriad of intracellular
      proteins and second messenger systems interact with each other, and are organized
      in pathways and networks to control cellular and tissue functions and cell fate
      decisions. This emerging ability to understand the basic mechanism controlling
      inter- and intra-cellular communication has provided an unprecedented opportunity
      to understand how their dysregulation contributes to the growth and dissemination
      of human cancers. Here, we will discuss the emerging information on how the use
      of modern technologies, including gene array and proteomic studies, combined with
      the molecular dissection of aberrant signaling networks, including the EGFR, ras,
      NFkappaB, Stat, Wnt/beta-catenin, TGF-beta, and PI3K-AKT-mTOR signaling pathways,
      can help elucidate the molecular mechanisms underlying HNSCC progression.
      Ultimately, we can envision that this knowledge may provide tremendous
      opportunities for the diagnosis of premalignant squamous lesions, and for the
      development of novel molecular-targeted strategies for the prevention and
      treatment of HNSCC.

PMID- 18805047
TI  - Comparison between conventional and intensity-modulated post-operative
      radiotherapy for stage III and IV oral cavity cancer in terms of treatment
      results and toxicity.
AB  - The aim of this study was to assess the treatment results and toxicity profiles
      of post-operative conventional radiotherapy (Conv-RT) and intensity-modulated
      radiotherapy (IMRT) for stage III and IV oral cavity cancer. During the period
      from April 2002 to December 2005, a total of 49 patients with stage III and IV
      squamous cell carcinoma of the oral cavity were treated with radical surgery
      followed by post-operative RT. Twenty-seven patients received Conv-RT while 22
      received IMRT. Only three patients received adjuvant chemotherapy. With a median
      follow-up time of 3.3 years, the 3-year overall survival and disease-free
      survival rates for patients who received Conv-RT vs IMRT were comparable. There
      was no significant difference in acute toxicity between the two different RT
      techniques. However, in terms of late toxicity, patients receiving IMRT had
      significantly less moderate to severe xerostomia and dysphagia than those
      receiving Conv-RT (36% vs 82%, p=0.01 for xerostomia and 21% vs 59%, p=0.02 for
      dysphagia). Post-operative Conv-RT and IMRT are equally effective in terms of
      tumor control for locally advanced oral cavity cancer. Patients receiving IMRT
      had comparable acute and significant less late toxicity than those receiving Conv
      RT.

PMID- 18805048
TI  - Growth and characterization of unidirectional (100) KDP single crystal by
      Sankaranarayanan-Ramasamy (SR) method.
AB  - Unidirectional (100) potassium dihydrogen orthophosphate (KDP) single crystals
      were grown by Sankaranarayanan-Ramasamy (SR) method. The (100) oriented seed
      crystals were mounted at the bottom of the glass ampoules and the crystals of
      20mm diameter, 30 mm height and 15 mm diameter, 65 mm height were grown by SR
      method. The grown crystals were characterized by high-resolution X-ray
      diffractometry anlaysis, UV-vis spectroscopy, dielectric and microhardness
      studies. The high-resolution X-ray diffractometry anlaysis indicates that the
      crystalline perfection is excellent without having any very low angle internal
      structural grain boundaries. The SR method-grown unidirectional KDP has 15%
      higher transmittance compared to conventional method-grown crystals. The
      dielectric constant was higher and the dielectric loss was less in SR method
      grown crystal. The crystals grown by SR method have much higher hardness value
      than conventional method-grown crystals. The quality of the crystal grown by SR
      method is better than conventional method-grown crystal.

PMID- 18805049
TI  - Lipid headgroups mediate organization and dynamics in bilayers.
AB  - We report on the fluorescence lifetime and anisotropy decay dynamics of the
      tethered chromophore NBD in unilamellar vesicles comprised of phosphoglycerol and
      phosphocholine lipids with C(12) and C(18) saturated acyl chains, with or without
      cholesterol and/or sphingomyelin. For the phosphocholine vesicles, we use the
      chromophore 2-(12-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)dodecanoyl-1
      hexadecanoyl-sn-glycero-3-phosphocholine (NBD-PC), and for the phosphoglycerol
      vesicles, we use the chromophore 2-(12-(7-nitrobenz-2-oxa-1,3-diazol-4
      yl)amino)dodecanoyl-1-hexadecanoyl-sn-glycero-3-[phospho-rac-(1-glycerol)] (NBD
      PG). The addition of cholesterol and/or sphingomyelin to the PC vesicles
      restricts the chromophore environment, in agreement with the known rigidizing
      effect of cholesterol on PC membranes. The PG systems do not exhibit an analogous
      effect with the addition of cholesterol and/or sphingomyelin. The motional
      freedom of the NBD chromophore is, in general, more restricted in the PC bilayers
      than it is in the PG bilayers, and we understand this behavior in the context of
      the role of the lipid headgroups in mediating bilayer organization.

PMID- 18805050
TI  - A proposed taxonomy for characterization and assessment of avian influenza
      outbreaks.
AB  - PURPOSE: The speed and high potential impact of avian influenza's (AI) on local
      bird populations, poultry economies and human health make timely and coordinated
      characterization, assessment and response to possible threats essential. To
      collaborate effectively, stakeholders (public health, medical, veterinary, and
      agricultural professionals) must be able to communicate and record findings,
      assessments, and actions in a standard fashion. We seek to discern a taxonomy of
      concepts and relationships that are important to the stakeholder community when
      sharing information about the characterization and assessment of an AI outbreak,
      according to a consistent and common perspective, interpretation, and level of
      detail. METHODS: To derive concepts relevant to AI characterization and
      assessment, we reviewed selected journal articles, reporting and laboratory
      forms, and public health websites associated with AI case reporting. We mapped
      concepts to existing medical terminologies within the Unified Medical Language
      System when possible, using the National Library of Medicine's MetaMap program.
      RESULTS: From 54 distinct information sources, we extracted 1113 concepts, of
      which 533 mapped to 15 medical terminologies; 580 did not map to specific
      terminologies. Using a combination of semantic type-relationship matching and
      expert consensus, we constructed the proposed taxonomy, with linkages to existing
      terminologies where pragmatic. CONCLUSION: The proposed taxonomy describes core
      knowledge, data and communication needs for the characterization and assessment
      of AI outbreaks in the context of existing medical terminologies across different
      domains. We also describe areas for further work.

PMID- 18805051
TI  - Evidence of human bocavirus circulating in children and adults, Cleveland, Ohio.
AB  - BACKGROUND: Viral respiratory illness is a major cause of morbidity and
      mortality. The human bocavirus (HBoV) is a recently recognized parvovirus
      isolated from human respiratory secretions. OBJECTIVES: To define the clinical
      and epidemiologic characteristics in adult and pediatric patients with evidence
      of HBoV. STUDY DESIGN: From October 2005 through October 2006, we screened
      respiratory samples from children and adults negative for common respiratory
      pathogens for HBoV by PCR. Demographic and clinical characteristics were obtained
      from medical records of HBoV positive individuals. RESULTS: Of 2075 samples
      screened, 1826 (88.0%) represented distinct respiratory events: 1539 (84.3%) were
      pediatric (<18 years), and 273 (15.0%) adult (> or =18 years). Forty (2.2%)
      patients had HBoV: 36 (2.3%) children and 4 (1.5%) adults. HBoV positive children
      had history of prematurity (31.3%) and cardiac disease (18.8%). Adults had
      underlying pulmonary (100%) and cardiac (50%) disease. Twenty-seven children
      (84.4%) were hospitalized; 9 (28.1%) required intensive care. All adults were
      hospitalized; none required intensive care. Nosocomial acquisition likely
      occurred in 3 patients. CONCLUSIONS: HBoV circulates in Cleveland, OH, in
      children and adults with similar frequencies, and can warrant hospitalization and
      intensive care. Further study would clarify our understanding of this newly
      recognized human pathogen.

PMID- 18805052
TI  - Characterization of the paracrine effects of human skeletal myoblasts
      transplanted in infarcted myocardium.
AB  - BACKGROUND: The discrepancy between the functional improvements yielded
      experimentally by skeletal myoblasts (SM) transplanted in infarcted myocardium
      and the paucity of their long-term engraftment has raised the hypothesis of cell
      mediated paracrine mechanisms. METHODS AND RESULTS: We analyzed gene expression
      and growth factors released by undifferentiated human SM (CD56(+)), myotubes (SM
      cultured until confluence) and fibroblasts-like cells (CD56(-)). Gene expression
      revealed up-regulation of pro-angiogenic (PGF), anti-apoptotics (BAG-1, BCL-2),
      heart development (TNNT2, TNNC1) and extracellular matrix remodelling (MMP-2, MMP
      7) genes in SM. In line with the gene expression profile, the analysis of culture
      supernatants of SM by ELISA identified the release of growth factors involved in
      angiogenesis (VEGF, PIGF, angiogenin, angiopoietin, HGF and PDGF-BB) as well as
      proteases involved in matrix remodelling (MMP2, MMP9 and MMP10) and their
      inhibitors (TIMPs). Culture of smooth muscle cells (SMC), cardiomyocytes (HL-1)
      and human umbilical vein endothelial cells (HUVECs) with SM-released conditioned
      media demonstrated an increased proliferation of HUVEC, SMC and cardiomyocytes
      (p<0.05) and a decrease in apoptosis of cardiomyocytes (p<0.05). Analysis of nude
      rats transplanted with human SM demonstrated expression of human-specific MMP-2,
      TNNI3, CNN3, PGF, TNNT2, PAX7, TGF-beta, and IGF-1 1 month after transplant.
      CONCLUSIONS: Our data support the paracrine hypothesis whereby myoblast-secreted
      factors may contribute to the beneficial effects of myogenic cell transplantation
      in infarcted myocardium.

PMID- 18805053
TI  - Influence of Home Monitoring on the clinical status of heart failure patients:
      Design and rationale of the IN-TIME study.
AB  - BACKGROUND: Despite optimal drug and device therapy, frequent hospitalisations
      due to decompensated heart failure remain an issue. Early detection of
      decompensation could prevent hospitalisation in patients with congestive heart
      failure. The recently introduced Home Monitoring functionality of implanted
      devices is a promising new telecardiology technique which provides information on
      the status of heart failure. Home Monitoring observation of heart failure
      patients could lead to early detection of preclinical decompensation, enable
      early intervention before clinical decompensation, and thus could prevent
      hospitalisations. OBJECTIVE: The IN-TIME study is designed to assess the impact
      of Home Monitoring on the early detection of worsening congestive heart failure
      and the clinical status of heart failure patients. STUDY DESIGN: Approximately
      620 patients will be prospectively randomised to patient management guided by
      Home Monitoring analysis or standard care and followed for 12 months. The
      endpoints committee will adjudicate events in a blinded fashion. The primary
      endpoint is a composite of all-cause mortality, unplanned hospitalisation due to
      worsening heart failure, NYHA class and patient global self assessment (Packer
      score). The study should complete recruitment during 2009 and report in late
      2010.

PMID- 18805054
TI  - Psychometric evaluation and tests of validity of the Medical Outcomes Study 12
      item Sleep Scale (MOS sleep).
AB  - OBJECTIVE: To validate the psychometric properties of the Medical Outcomes Study
      (MOS) Sleep Scale in subjects with restless legs syndrome (RLS). METHODS: Data
      from a clinical trial program involving two Phase III, double-blind, placebo
      controlled trials of ropinirole in subjects with moderate-to-severe primary RLS
      were analyzed. Subjects were assessed on the MOS Sleep Scale at baseline, Weeks 8
      and 12. RESULTS: The baseline validation population included 551 subjects on
      which full longitudinal data are available. Psychometric assessment of four MOS
      sleep domains revealed satisfactory item convergent validity (r > 0.40) for most
      items. All domain items in both trials surpassed the standard for item
      discriminant validity, with no significant floor or ceiling effects. The MOS
      sleep domain scores showed good internal consistency reliability. Concurrent
      validity (r = 0.40) was exceeded in correlations between the RLS overall quality
      of-life score and sleep problems index II. The clinical validity of the MOS Sleep
      Scale was demonstrated against self-reported RLS symptoms and clinician
      determined severity; changes in MOS Sleep Scale were responsive to improvements
      in RLS severity, as measured by the Clinical Global Impression-Improvement and
      Severity-of-Illness scales. CONCLUSION: The MOS Sleep Scale is a reliable, valid
      tool for assessing changes in the sleep of subjects with moderate-to-severe
      primary RLS. The somnolence domain failed to relate to clinical severity of RLS,
      indicating a possible sleep-wake relationship unique to RLS. Use of this scale to
      evaluate other conditions causing sleep disturbance is supported.

PMID- 18805055
TI  - Phase advancing the human circadian clock with blue-enriched polychromatic light.
AB  - BACKGROUND: Previous studies have shown that the human circadian system is
      maximally sensitive to short-wavelength (blue) light. Whether this sensitivity
      can be utilized to increase the size of phase shifts using light boxes and
      protocols designed for practical settings is not known. We assessed whether
      bright polychromatic lamps enriched in the short-wavelength portion of the
      visible light spectrum could produce larger phase advances than standard bright
      white lamps. METHODS: Twenty-two healthy young adults received either a bright
      white or bright blue-enriched 2-h phase advancing light pulse upon awakening on
      each of four treatment days. On the first treatment day the light pulse began 8h
      after the dim light melatonin onset (DLMO), on average about 2h before baseline
      wake time. On each subsequent day, light treatment began 1h earlier than the
      previous day, and the sleep schedule was also advanced. RESULTS: Phase advances
      of the DLMO for the blue-enriched (92+/-78 min, n=12) and white groups (76+/-45
      min, n=10) were not significantly different. CONCLUSION: Bright blue-enriched
      polychromatic light is no more effective than standard bright light therapy for
      phase advancing circadian rhythms at commonly used therapeutic light levels.

PMID- 18805056
TI  - Mycotoxins and child health: the need for health risk assessment.
AB  - The occurrences of mycotoxins as food contaminants in different localities
      particularly in developing countries and the inevitable exposure of populations
      and children to these toxins with probable adverse outcomes need be
      scientifically and systematically assessed. Health risk assessment developed in
      the 1980s is separate from risk management, both with risk communication form the
      risk analysis framework adopted by the World Health Organization. The process
      contributes increasingly to policy development, public health decision making,
      the establishment of mycotoxin regulations and research planning. However, the
      exercise of the risk assessment structured approach is not simple and is faced up
      to lack of data, capable infrastructure facilities and need for trained personnel
      and resources. Furthermore, adopted methodologies need be developed focusing on
      child characteristics and health concerns.

PMID- 18805058
TI  - Adolescent varicocelectomy: postoperative catch-up growth is not secondary to
      lymphatic ligation.
AB  - PURPOSE: The major indication for adolescent varicocelectomy is testicular
      asymmetry with the left testicle smaller than the right. Catch-up growth
      following surgery is one of the parameters used to assess efficacy of surgery.
      However, it is not clear whether this represents true tissue growth or increased
      interstitial fluid secondary to lymphatic obstruction. The purpose of this study
      was to compare catch-up growth in patients who underwent varicocelectomy with and
      without lymphatic preservation. MATERIALS AND METHODS: We retrospectively
      analyzed the outcomes of 136 boys (mean age 15.1years) who had 10% or greater
      preoperative testicular asymmetry and underwent varicocelectomy between 1997 and
      2006. Surgery was either a laparoscopic nonlymphatic sparing or laparoscopic
      lymphatic sparing varicocelectomy. All patients had pre- and postoperative
      ultrasound volume measurements at least 6months following surgery. The groups
      were compared for incidence of postoperative catch-up growth, achieving less than
      10% testicular asymmetry. RESULTS: After a mean follow up of 24.7months, catch-up
      growth was achieved in 62.8% of patients. There was no significant difference
      between the groups in regard to catch-up growth (51.7% vs 66.3%, P=0.193).
      CONCLUSIONS: Since no significant difference was found between the laparoscopic
      nonlymphatic sparing and laparoscopic lymphatic sparing varicocelectomies, we
      conclude that lymphatic obstruction is not the cause of catch-up growth.

PMID- 18805059
TI  - Lumbar fusion outcomes stratified by specific diagnostic indication.
AB  - BACKGROUND: One of the primary difficulties in evaluating the effectiveness of
      lumbar fusion is that, with the exception of spondylolisthesis, specific
      diagnostic indications for surgery are poorly defined. Diagnostic specificity
      beyond the symptom of low back pain or the presence of lumbar degeneration needs
      to be delineated such that outcomes data can be effectively translated into
      clinical decision making or evidence-based guidelines. PURPOSE: The purpose of
      this study was to report on prospectively collected clinical outcome measures,
      stratified by diagnosis, among a series of patients with lumbar degenerative
      disease whose treatment included lumbar spine fusion. STUDY DESIGN: Demographics,
      diagnostic categorization, and clinical outcome measures were prospectively
      collected by six spine surgeons at a single tertiary spine center, as part of the
      surgeons' standard clinical practice. PATIENT SAMPLE: Four hundred and twenty
      eight patients were enrolled in the study and complete 1- and 2-year Health
      Related Quality of Life (HRQOL) data were available in 327 patients whose
      treatment included decompression and posterolateral lumbar fusion. OUTCOME
      MEASURES: The Oswestry Disability Index (ODI), Short Form-36 (SF-36), numeric
      rating scales for back pain and leg pain. METHODS: Preoperative diagnosis was
      classified, in the primary surgical cases, as disc pathology, spondylolisthesis,
      instability, stenosis, or scoliosis. In revision cases, the diagnosis was
      classified as nonunion, adjacent level degeneration, or postdiscectomy revision.
      Patient-reported outcomes at 1 and 2 years post-op were assessed based on
      diagnostic stratification. Statistical evaluation of clinical outcome was
      performed for both mean net change in outcome scores and the percentage of
      patients reaching a minimum clinically important difference (MCID) threshold for
      each outcome measure. RESULTS: Preoperative diagnosis was spondylolisthesis
      (n=80), scoliosis (n=17), disc pathology (n=33), instability (n=21), stenosis
      (n=46), postdiscectomy revision (n=67), adjacent level degeneration (n=40), or
      nonunion (n=23). Evaluation of 2-year post-op HRQOL measures by diagnostic
      subgroup revealed the most substantial improvement in ODI score for patients with
      spondylolisthesis (22.7 points) and scoliosis (21.2 points). Patients with the
      diagnosis of disc pathology (16.2 points), postdiscectomy revision (14.0 points),
      instability (12.7 points), stenosis (10.6 points), and adjacent level
      degeneration (9.5 points) demonstrated a progressively smaller magnitude of ODI
      improvement. The least ODI improvement at 2 years after surgery was seen in
      patients with nonunion of a prior fusion (5.5 points). The percentage of patients
      reaching MCID for ODI at 2 years post-op ranged from 71.0% in the
      spondylolisthesis subgroup to 34.8% in the nonunion subgroup. The greatest SF-36
      physical component score improvement at 2-year follow-up was seen in patients
      with disc pathology (7.9 points) and spondylolisthesis (7.7 points), followed by
      scoliosis (6.6 points) and stenosis (6.5 points), instability (5.6 points),
      postdiscectomy revision (5.3 points) nonunion (3.1 points) and adjacent level
      degeneration (2.5 points). No significant changes from Year 1 to Year 2 were
      noted in any of the subgroups. For SF-36 physical component score, percentage of
      patients reaching MCID ranged from 63.6% in the disc pathology subgroup to 25% in
      the nonunion subgroup. CONCLUSIONS: This study supports the concept that added
      diagnostic specificity is a critical component in building an improved evidence
      base for lumbar fusion surgery. The magnitude of HRQOL improvement was not equal
      among diagnostic subgroups. The percentage of patients reaching an MCID level of
      improvement was also significantly influenced by diagnostic stratification.
      Without diagnostic specificity for entities beyond spondylolisthesis, the absence
      of well-defined study populations will continue to limit our ability to move
      toward evidence-based decision making.

PMID- 18805060
TI  - A porcine collagen-derived matrix as a carrier for recombinant human bone
      morphogenetic protein-2 enhances spinal fusion in rats.
AB  - BACKGROUND CONTEXT: Recombinant bone morphogenetic proteins (rhBMPs) have been
      used successfully in clinical trials. However, large doses of rhBMPs were
      required to induce adequate bone repair. Collagen sponges (CSs) have failed to
      allow a more sustained release of rhBMPs. Ongoing research aims to design
      carriers that allow a more controlled and sustained release of the protein. E
      Matrix is a injectable scaffold matrix that may enhance rhBMP activity and
      stimulate bone regeneration. PURPOSE: The purpose of this study was to test E
      Matrix as a carrier for rhBMPs in a CS and examine its feasibility in clinical
      applications by using a rat spinal fusion model. PATIENT SAMPLE: A total of 80
      Lewis rats aged 8-16 weeks were divided into nine groups. STUDY DESIGN/SETTING:
      Rat spinal fusion model. OUTCOME MEASURES: Radiographs were obtained at 4, 6, and
      8 weeks. The rats were sacrificed and their spines were explanted and assessed by
      manual palpation, high-resolution microcomputed tomography (micro-CT), and
      histologic analysis. METHODS: Group I animals were implanted with CS alone
      (negative control); Group II animals with CS containing 10microg rhBMP-2
      (positive control); Group III animals with CS containing 3microg rhBMP-2; Group
      IV animals with CS containing 3microg rhBMP-2 and E-Matrix; Group V animals with
      CS containing 1microg rhBMP-2; Group VI animals with CS containing 1microg rhBMP
      2 and E-Matrix; Group VII animals with CS containing 0.5microg rhBMP-2; Group
      VIII animals with CS containing 0.5microg rhBMP-2 and E-Matrix; and Group IX
      animals with CS and E-Matrix without rhBMP-2. RESULTS: Radiographic evaluation,
      micro-CT, and manual palpation revealed spinal fusion in all rats in the BMP-2
      and E-Matrix groups (IV, VI, and VIII) and high-dose BMP-2 groups (II and III).
      Four spines in the 3microg rhBMP-2 group (V) fused, and one spine in the
      0.5microg rhBMP-2 group (VII) exhibited fusion. No spines were fused in Groups I
      (CS alone) and IX (E-Matrix alone). The volume of new bone in the area between
      the tip of the L4 transverse process and the base of the L5 transverse process in
      Group IV was equivalent to the volumes observed in Group II. CONCLUSION: E-matrix
      enhances spinal fusion as a carrier for rhBMP-2 in a rat spinal fusion model. The
      results of this study suggest that E-Matrix as a growth factor carrier may be
      applicable to spinal fusion and may improve rhBMP-2's activity at the fusion
      site.

PMID- 18805061
TI  - Physical demand levels in individuals completing a sports performance-based work
      conditioning/hardening program after lumbar fusion.
AB  - BACKGROUND CONTEXT: Pain and disability after lumbar fusion surgery contributes
      to the over $20 billion dollars spent in health-care costs and estimated $28
      billion in lost wages annually. With the goal of returning to work, an intensive
      program designed to build functional strength may be used. Previous interventions
      for this subgroup report the outcome measure of return to work (RTW), but do not
      account for the physical demand of the job to which they are returning. This may
      account for varying RTW and re-injury rates. PURPOSE: To examine the
      effectiveness of a sports performance-based work conditioning/hardening (SPWC/H)
      program on increasing an individual's strength measured by achievement of
      physical demand level (PDL) job classification of individuals followed by
      workers' compensation having had lumbar fusion surgery. STUDY DESIGN/SETTING: An
      uncontrolled multicenter, retrospective observational study of visits from 1999
      2002 in an outpatient physical therapy setting. PATIENT SAMPLE: Fifty-four
      patients having undergone lumbar fusion surgery, managed by workers'
      compensation, that successfully completed a SPWC/H program. OUTCOME MEASURE:
      Physiologic measures: Deadlift and overhead press lifts, defined as maximum
      weight, a patient is able to lift between 8 and 15 repetitions. Functional
      measures: Calculated deadlift and overhead press volume (DLv, OHv) and estimated
      one repetition maximum (DLm, OHm). Physical demand level (PDL) for first (pre)
      and last week (post) are defined as: light (L<20lb occasionally), light/medium
      (LM>20lb occasionally), medium (M, 50lb occasionally), medium heavy (MH, 75lb
      occasionally), heavy (H, 100lb occasionally), and very heavy (VH>100lb
      occasionally), where 'occasionally' for the purposes of this article, is defined
      as in the 8-15 repetition range. METHODS: Patients completed a greater than or
      equal to 4 week, 4-5 days/wk, SPWC/H program. This program combines traditional
      concepts of strength and endurance training of work conditioning (WC) and
      hardening (WH) programs, with the sports performance concept of periodization in
      resistance training volume and intensity. Best set overhead and press lifts were
      obtained from each patient during the first and last week of the program.
      RESULTS: Significant increase between pre- and post-DLv, DLm, OHv, and OHm (all
      p<0.0001) existed when grouping all subjects. When adjacent groups are merged
      into M/MH and H/VH, significant differences existed between groups and pre- and
      postlifts (p<0.05). There was a median increase of three classifications when
      grouping by pre-PDL. There was no difference in outcomes found by grouping by
      single or multiple levels fused. Overall, numbers in each starting PDL were: 41
      (75.9%) light, 6 (11.1%) LM, and 7 (13%) in medium. Numbers ending in each PDL
      group were: 1 (1.9%) light, 2 (3.7%) LM, 7 (13%) medium, 19 (35.2%) medium/heavy,
      5 (9.3%) heavy, and 20 (37%) at very high. CONCLUSIONS: Post-lumbar spinal fusion
      patients are typically at the light PDL (<20lb occasionally) on completion of
      traditional physical therapy program. After an SPWC/H program, significant
      increase strength of deadlift and overhead lift volume and one repetition maximum
      demonstrated a median three-level increase in classification of PDL. We were also
      able to determine that there was no difference in strength outcome between those
      with a single- vs. multiple-level fusion surgery. Although the vast majority of
      individuals entered the program at the lowest PDL (20lb or less occasionally),
      more than 80% of patients completed the program at PDL of medium (50lb
      occasionally) or above, and 37% of patients achieved the maximum PDL (over 100lb
      occasionally). Future studies are needed to determine if increases in strength
      determined by PDL classification such as these relates to increased RTW rates and
      decreased re-injury rates.

PMID- 18805062
TI  - Esthesioneuroblastoma metastatic to the thoracic intradural and extradural space.
AB  - BACKGROUND CONTEXT: Ethesioneuroblastoma (ENB) is a rare tumor of the olfactory
      epithelium that has been shown to metastasize mostly to the cervical lymphatics,
      with only infrequent spread to other locations. We report a rare case of ENB
      characterized by recurrence and distant metastasis to the T7-T8 intradural and
      extradural space. PURPOSE: To report a rare case of recurrent ENB metastatic to
      the thoracic intradural and extradural space. STUDY DESIGN/SETTING: Case report
      with a review of the literature. METHODS: A 64-year-old man with recurrent ENB
      presented with chronic pain in the neck, shoulder, and back. His neurologic exam
      was normal. Computed tomography of the chest showed no pulmonary metastasis and a
      high-attenuation spinal canal mass at T8 was noted on magnetic resonance imaging.
      A laminectomy at T7-T8 was performed for resection of a large epidural mass. A
      tumor was seen penetrating through the dura, and a midline durotomy was performed
      for resection of a large intradural mass. Frozen section and permanent stains
      were consistent with metastatic ENB. RESULTS: The postoperative period was
      uneventful, and included pain management and physical therapy, followed by
      chemotherapy and radiation. The patient remains free of spinal recurrence 2 years
      after surgery. CONCLUSIONS: Metastasis of ENB to the spinal column is rare, and
      of those instances, 80% are localized to the cauda equina. Recurrent ENB
      metastatic to the thoracic intradural and extradural space is extremely rare, and
      was successfully treated with surgical resection.

PMID- 18805063
TI  - The use of allograft bone in spine surgery: is it safe?
AB  - BACKGROUND CONTEXT: Allograft bone is commonly used in various spinal surgeries.
      The large amount of recalled allograft tissue, particularly in recent years, has
      increased concerns regarding the safety of allograft bone for spinal surgery. An
      analysis of allograft recall and its safety in spinal surgery has not been
      reported previously. PURPOSE: To determine 1) the number and types of allograft
      recall and the reasons for recall, 2) the types of disease transmission to spine
      patients, and 3) assess the safety of allograft bone in spinal surgery. STUDY
      DESIGN/SETTING: Retrospective review. METHODS: A retrospective review of all Food
      and Drug Administration (FDA) data from 1994 to June 2007 was reviewed to
      determine the amount and types of recalled allograft tissue. The literature and
      data from the Center for Disease Control were reviewed to determine the number
      and types of disease transmissions from allograft bone that have occurred to
      spine surgery patients during the study period. RESULTS: There were 59,476
      musculoskeletal allograft tissue specimens recalled by FDA during the study
      period, which accounts for 96.5% of all allograft tissue recalled in the United
      States. Improper donor evaluation, contamination, and recipient infections are
      the main reasons for allograft recall. There has been one case of human
      immunodeficiency virus infection transmission to a spine surgery patient in 1988.
      This is the only reported case of viral transmission. There are no reports of
      bacterial disease transmission from the use of allograft bone to spine surgery
      patients. CONCLUSIONS: The precise number of allografts used in spine surgery
      annually and the precise incidence of disease transmission to spine surgery
      patients linked to the use of allograft tissue is unknown. Musculoskeletal
      allograft tissue accounts for the majority of recalled tissue by FDA. Despite the
      large number of allograft recalls in this country, there is only one documented
      case in the literature of disease transmission to a spine surgery patient. There
      appears to be no overt risk associated with the use of allograft bone in spine
      surgery. However, as discussed in this article, there are certain aspects
      regarding the use of allograft bone that should be considered.

PMID- 18805064
TI  - After surgery, evolution of quality of life in lumbar canal stenosis patients.

PMID- 18805065
TI  - The confusion of important literature review.

PMID- 18805067
TI  - Laminoplasty: a review of its role in compressive cervical myelopathy.

PMID- 18805066
TI  - Prospective, randomized, multicenter Food and Drug Administration investigational
      device exemption study of lumbar total disc replacement with the CHARITE
      artificial disc versus lumbar fusion: five-year follow-up.
AB  - BACKGROUND CONTEXT: The CHARITE artificial disc, a lumbar spinal arthroplasty
      device, was approved by the United States Food and Drug Administration in 2004
      based on two-year safety and effectiveness data from a multicenter, prospective,
      randomized investigational device exemption (IDE) study. No long-term,
      randomized, prospective study on the CHARITE disc or any other artificial disc
      has been published to date. PURPOSE: The purpose of this study was to compare the
      safety and effectiveness at the five-year follow-up time point of lumbar total
      disc replacement using the CHARITE artificial disc (DePuy Spine, Raynham, MA)
      with that of anterior lumbar interbody fusion (ALIF) with BAK cages and iliac
      crest autograft, for the treatment of single-level degenerative disc disease from
      L4 to S1, unresponsive to nonoperative treatment. STUDY DESIGN/SETTING:
      Randomized controlled trial-five-year follow-up. PATIENT SAMPLE: Ninety CHARITE
      patients and 43 BAK patients. OUTCOME MEASURES: Self-reported measures: visual
      analog scale (VAS); validated Oswestry disability index (ODI version 1.0); Short
      Form 36 Questionnaire, and patient satisfaction. Physiologic measures:
      radiographic range of motion, disc height, and segmental translation. Functional
      measures: work status. METHODS: Of the 375 subjects enrolled in the CHARITE IDE
      trial, 277 were eligible for the five-year study and 160 patients thereof
      completed the five-year follow-up. The completers included 133 randomized
      patients. Overall success was defined as improvement> or =15 pts in ODI vs.
      baseline, no device failure, absence of major complications, and maintenance or
      improvement of neurological status. Additional clinical outcomes included an ODI
      questionnaire as well as VAS, SF-36, and patient satisfaction surveys. Work
      status was tracked for all patients. Safety assessments included occurrence and
      severity of adverse events and device failures. Radiographic analyses such as
      index- and adjacent-level range of motion, segmental translation, disc height,
      and longitudinal ossification were also carried out. RESULTS: Overall success was
      57.8% in the CHARITE group vs. 51.2% in the BAK group (Blackwelder's test:
      p=0.0359, Delta=0.10). In addition, mean changes from baseline for ODI (CHARITE: 
      24.0 pts vs. BAK: -27.5 pts), VAS pain scores (CHARITE: -38.7 vs. BAK: -40.0),
      and SF-36 questionnaires (SF-36 Physical Component Scores [PCS]: CHARITE: 12.6
      pts vs. BAK: 12.3 pts) were similar across groups. In patient satisfaction
      surveys, 78% of CHARITE patients were satisfied vs. 72% of BAK patients. A total
      of 65.6% patients in the CHARITE group vs. 46.5% patients in the BAK group were
      employed full-time. This difference was statistically significant (p=0.0403).
      Long-term disability was recorded for 8.0% of CHARITE patients and 20.9% of BAK
      patients, a difference that was also statistically significant (p=0.0441).
      Additional index-level surgery was performed in 7.7% of CHARITE patients and
      16.3% of BAK patients. Radiographic findings included operative and adjacent
      level range of motion (ROM), intervertebral disc height and segmental
      translation. At the five-year follow-up, the mean ROM at the index level was 6.0
      degrees for CHARITE patients and 1.0 degrees for BAK patients. Changes in disc
      height were also similar for both CHARITE and BAK patients (0.7 mm for both
      groups, p=0.9827). Segmental translation was 0.4 and 0.8mm in patients implanted
      with CHARITE at L4-L5 vs. L5-S1, respectively, and 0.1mm in BAK patients.
      CONCLUSIONS: The results of this five-year, prospective, randomized multicenter
      study are consistent with the two-year reports of noninferiority of CHARITE
      artificial disc vs. ALIF with BAK and iliac crest autograft. No statistical
      differences were found in clinical outcomes between groups. In addition, CHARITE
      patients reached a statistically greater rate of part- and full-time employment
      and a statistically lower rate of long-term disability, compared with BAK
      patients. Radiographically, the ROMs at index- and adjacent levels were not
      statistically different from those observed at two-years postsurgery.

PMID- 18805068
TI  - Diffusion of 2,2,6,6-tetramethylpiperidine 1-oxyl derivatives of variable
      hydrophobicity in tropocollagen I solution.
AB  - Electrochemical time-of-flight was used to measure the diffusion coefficients of
      2,2,6,6-tetramethylpiperidine 1-oxyl derivatives, C(n)TPA, (3 to 7 CH(2) groups),
      in tropocollagen I solution, as a function of the chain length and the cross
      linking with glutaraldehyde. The values of the diffusion coefficient of C(n)TPA
      in pure aqueous electrolyte follow the Stokes-Einstein law, i.e. the diffusion
      coefficient is inversely proportional to the size of the redox probe. Different
      behavior is observed in 0.5% (w/v) tropocollagen solution where the molecules
      with longer alkyl chains show larger diffusion coefficients than the smaller
      molecules. This behavior is explained in terms of electrostatic interactions
      between tropocollagen chains and the C(n)TPA molecules. The measurements of the
      diffusion coefficients of C(n)TPA in 0.5% tropocollagen cross-linked with
      glutaraldehyde indicate that while the C(7)TPA and C(5)TPA probes exhibit lower
      diffusion coefficients upon addition of 0.05% GA and 0.1% (v/v) GA respectively,
      the other C(n)TPA molecules exhibit either unchanged or increased diffusion
      coefficients under the same conditions thus indicating the presence of
      hydrophobic pockets selectively interacting with C(n)TPAs. These results
      demonstrate the utility of electrochemical time-of-flight in measurements of
      diffusion coefficients in complex biopolymeric media.

PMID- 18805069
TI  - Bioelectrochemistry. Cellular electrochemistry, proceedings of the XIXth
      International Symposium on Bioelectrochemistry and Bioenergetics.

PMID- 18805070
TI  - Facile electrocatalytic redox of hemoglobin by flower-like gold nanoparticles on
      boron-doped diamond surface.
AB  - The flower-like gold nanoparticles together with spherical and convex polyhedron
      gold nanoparticles were fabricated on boron-doped diamond (BDD) surface by one
      step and simple electrochemical method through easily controlling the applied
      potential and the concentration of HAuCl(4). The recorded X-ray diffraction (XRD)
      patterns confirmed that these three shapes of gold nanoparticles were dominated
      by different crystal facets. The cyclic voltammetric results indicated that the
      morphology of gold nanoparticles plays big role in their electrochemical
      behaviors. The direct electrochemistry of hemoglobin (Hb) was realized on all the
      three different shapes of nanogold-attached BDD surface without the aid of any
      electron mediator. In pH 4.5 acetate buffer solutions (ABS), Hb showed a pair of
      well defined and quasi-reversible redox peaks. However, the results obtained
      demonstrated that the redox peak potential, the average surface concentration of
      electroactive heme, and the electron transfer rates of Hb are greatly dependent
      upon the surface morphology of gold nanoparticles. The electron transfer rate
      constant of hemoglobin over flower-like nanogold/BDD electrode was more than two
      times higher than that over spherical and convex polyhedron nanogold. The
      observed differences may be ascribed to the difference in gold particle
      characteristics including surface roughness, exposed surface area, and crystal
      structure.

PMID- 18805071
TI  - A SEC-HPLC-ICP MS hyphenated technique for identification of sulfur-containing
      arsenic metabolites in biological samples.
AB  - The present study describes the synthesis and characterization of thioarsenicals
      using electro-spray ionization-MS and time of flight-MS. Separation of
      thioarsenicals was found to be better by size-exclusion column compared to anion
      exchange column coupled with HPLC-inductively coupled argon plasma mass
      spectrometer (ICP MS). Although four thioarsenicals were confirmed as
      dimethylthioarsinous acid (m/z=138), methylmonothioarsonous acid (m/z=122),
      dimethyldithioarsinic acid (m/z=170) and methyltrithioarsonic acid (m/z=188), it
      is noted that HPLC-ICP MS alone were not sufficient for their identification.
      Also, none of them was stable with time. This is the first report detailing the
      synthesis and identification of methyltrithioarsonic acid. Both
      dimethyldithioarsinic acid and dimethylthioarsinous acid were detected in human
      nail samples while dimethyldithioarsinic acid was found in urine samples. So, the
      above technique could be applicable to the identification of sulfur-containing
      biomolecules in the biological samples.

PMID- 18805072
TI  - An automated, highly sensitive LC-MS/MS assay for the quantification of the
      opiate antagonist naltrexone and its major metabolite 6beta-naltrexol in dog and
      human plasma.
AB  - To support animal studies and clinical pharmacokinetic trials, we developed and
      validated an automated, specific and highly sensitive LC-MS/MS method for the
      quantification of naltrexone and 6beta-naltrexol in the same run. In human
      plasma, the assay had a lower limit of quantitation of only 5pg/mL. This was of
      critical importance to follow naltrexone pharmacokinetics during its terminal
      elimination phase. The assay had the following key performance characteristics
      for naltrexone in human plasma: range of reliable quantification: 0.005-100ng/mL
      (r2>0.99), inter-day accuracy (0.03ng/mL): 103.7% and inter-day precision: 10.1%.
      There were no ion suppression, matrix interferences or carry-over.

PMID- 18805073
TI  - High-performance liquid chromatography coupled with electrospray tandem mass
      spectrometry (LC/MS/MS) method for the simultaneous determination of diazepam,
      atropine and pralidoxime in human plasma.
AB  - A high-performance liquid chromatography coupled with electrospray tandem mass
      spectrometry (LC/MS/MS) procedure for the simultaneous determination of diazepam
      from avizafone, atropine and pralidoxime in human plasma is described. Sample
      pretreatment consisted of protein precipitation from 100microl of plasma using
      acetonitrile containing the internal standard (diazepam D5). Chromatographic
      separation was performed on a X-Terra MS C8 column (100mmx2.1mm, i.d. 3.5microm),
      with a quick stepwise gradient using a formate buffer (pH 3, 2mM) and
      acetonitrile at a flow rate of 0.2ml/min. The triple quadrupole mass spectrometer
      was operated in positive ion mode and multiple reaction monitoring was used for
      drug quantification. The method was validated over the concentration ranges of 1
      500ng/ml for diazepam, 0.25-50ng/ml for atropine and 5-1000ng/ml for pralidoxime.
      The coefficients of variation were always <15% for both intra-day and inter-day
      precision for each analyte. Mean accuracies were also within +/-15%. This method
      has been successfully applied to a pharmacokinetic study of the three compounds
      after intramuscular injection of an avizafone-atropine-pralidoxime combination,
      in healthy subjects.

PMID- 18805074
TI  - Purification of recombinant rotavirus VP7 glycoprotein for the study of in vitro
      rotavirus-like particles assembly.
AB  - Rotavirus VP7 is a glycoprotein that forms the viral capsid outerlayer and is
      essential to the correct assembly of triple-layered rotavirus-like particles
      (RLPs). In this work, a novel purification strategy was designed to allow
      obtaining highly pure monomeric VP7 required for the RLPs in vitro assembly. VP7
      production kinetics in baculovirus-insect cells at cell concentration at
      infection (CCI) of 1x10(6)cellsmL(-1) was compared in terms of VP7/glycoprotein
      64 (gp64) ratio at different multiplicity of infection (MOI). The best
      productivity was achieved at MOI of 0.1plaque forming unit (pfu)cell(-1) and time
      of harvest of 80h post-infection. After preliminary clarification steps, the
      proteins eluted from Concanavalin A were concentrated and loaded onto size
      exclusion chromatography. The polishing step was anion exchange chromatography
      with Mono Q. The high resolution of this column resulted in separation of
      monomers from dimers of VP7. Overall, the purification protocol yielded high
      level of purity (>90%). Purified VP7 was characterized by MALDI-TOF mass
      spectrometry and SDS-capillary gel electrophoresis. The MW and apparent MW were
      determined as 31.6 and 39kDa, respectively, confirming the efficacy of the
      proposed purification strategy that now enables RLPs assembly studies.

PMID- 18805075
TI  - Star and comet incisions for skin-sparing mastectomy.

PMID- 18805077
TI  - Proximally located partial skin-paddle necrosis in the gracilis musculocutaneous
      flap.

PMID- 18805078
TI  - Gigantomastia--definition and association with hypercalcaemia.

PMID- 18805079
TI  - Small RNA regulators of gene expression.
AB  - This year, the Lasker Foundation recognizes Victor Ambros, Gary Ruvkun, and David
      Baulcombe for their pioneering work elucidating the role of short RNA species in
      the posttranscriptional regulation of eukaryotic gene expression.

PMID- 18805080
TI  - The discovery of statins.
AB  - This year, the Lasker Foundation confers its Clinical Medical Research Award on
      Akira Endo for his isolation from fungi of statins, potent inhibitors of
      cholesterol synthesis in the liver. The introduction of statins to clinical
      practice has markedly reduced morbidity and mortality from atherosclerotic
      cardiovascular disease.

PMID- 18805081
TI  - Lasker-Koshland Award to 21st century microbe master.
AB  - The 2008 Lasker-Koshland Award will be presented to Stanley Falkow, one of the
      legendary figures in the history of microbiology research. Falkow's many
      contributions remade the way we think about bacterial pathogens, antibiotic
      resistance, and infectious disease.

PMID- 18805082
TI  - Putting a notch in our understanding of nuclear migration.
AB  - The nuclei of progenitor cells in developing neural epithelia change their
      position during the cell cycle through a process called interkinetic nuclear
      migration. Del Bene et al. (2008) report that defects in the machinery
      controlling this process lead to altered exposure to Notch signals and systemic
      effects on neurogenesis in the retina.

PMID- 18805083
TI  - Fat talks, liver and muscle listen.
AB  - Fat metabolism and glucose homeostasis are processes that are highly
      interconnected. Cao et al. (2008) now take this concept a step further by
      identifying a fatty acid metabolite generated in adipose tissue that regulates
      insulin sensitivity in liver and muscle.

PMID- 18805084
TI  - Grasping at origins.
AB  - Chromosome segregation in the bacterium Caulobacter crescentus involves
      propulsion of the replication origin and its capture at one pole of the cell.
      Bowman et al. (2008) and Ebersbach et al. (2008) now report the discovery of a
      protein called PopZ that mediates this chromosome capture.

PMID- 18805085
TI  - Kinesin motors: no strain, no gain.
AB  - The processive movement of the dimeric motor protein kinesin 1 along microtubules
      requires communication between the two motor domains. Yildiz et al. (2008) now
      show that tension between the motor domains not only is necessary for normal
      processivity but also may be sufficient for motor motility under some conditions.

PMID- 18805086
TI  - Retinoic acid synthesis and signaling during early organogenesis.
AB  - Retinoic acid, a derivative of vitamin A, is an essential component of cell-cell
      signaling during vertebrate organogenesis. In early development, retinoic acid
      organizes the trunk by providing an instructive signal for posterior
      neuroectoderm and foregut endoderm and a permissive signal for trunk mesoderm
      differentiation. At later stages, retinoic acid contributes to the development of
      the eye and other organs. Recent studies suggest that retinoic acid may act
      primarily in a paracrine manner and provide insight into the cell-cell signaling
      networks that control differentiation of pluripotent cells.

PMID- 18805087
TI  - Identification of a lipokine, a lipid hormone linking adipose tissue to systemic
      metabolism.
AB  - Dysregulation of lipid metabolism in individual tissues leads to systemic
      disruption of insulin action and glucose metabolism. Utilizing quantitative
      lipidomic analyses and mice deficient in adipose tissue lipid chaperones aP2 and
      mal1, we explored how metabolic alterations in adipose tissue are linked to whole
      body metabolism through lipid signals. A robust increase in de novo lipogenesis
      rendered the adipose tissue of these mice resistant to the deleterious effects of
      dietary lipid exposure. Systemic lipid profiling also led to identification of
      C16:1n7-palmitoleate as an adipose tissue-derived lipid hormone that strongly
      stimulates muscle insulin action and suppresses hepatosteatosis. Our data reveal
      a lipid-mediated endocrine network and demonstrate that adipose tissue uses
      lipokines such as C16:1n7-palmitoleate to communicate with distant organs and
      regulate systemic metabolic homeostasis.

PMID- 18805088
TI  - A polymeric protein anchors the chromosomal origin/ParB complex at a bacterial
      cell pole.
AB  - Bacterial replication origins move towards opposite ends of the cell during DNA
      segregation. We have identified a proline-rich polar protein, PopZ, required to
      anchor the separated Caulobacter crescentus chromosome origins at the cell poles,
      a function that is essential for maintaining chromosome organization and normal
      cell division. PopZ interacts directly with the ParB protein bound to specific
      DNA sequences near the replication origin. As the origin/ParB complex is being
      replicated and moved across the cell, PopZ accumulates at the cell pole and
      tethers the origin in place upon arrival. The polar accumulation of PopZ occurs
      by a diffusion/capture mechanism that requires the MreB cytoskeleton. High
      molecular weight oligomers of PopZ assemble in vitro into a filamentous network
      with trimer junctions, suggesting that the PopZ network and ParB-bound DNA
      interact in an adhesive complex, fixing the chromosome origin at the cell pole.

PMID- 18805089
TI  - A self-associating protein critical for chromosome attachment, division, and
      polar organization in caulobacter.
AB  - Cell polarization is an integral part of many unrelated bacterial processes. How
      intrinsic cell polarization is achieved is poorly understood. Here, we provide
      evidence that Caulobacter crescentus uses a multimeric pole-organizing factor
      (PopZ) that serves as a hub to concurrently achieve several polarizing functions.
      During chromosome segregation, polar PopZ captures the ParB*ori complex and
      thereby anchors sister chromosomes at opposite poles. This step is essential for
      stabilizing bipolar gradients of a cell division inhibitor and setting up
      division near midcell. PopZ also affects polar stalk morphogenesis and mediates
      the polar localization of the morphogenetic and cell cycle signaling proteins
      CckA and DivJ. Polar accumulation of PopZ, which is central to its polarizing
      activity, can be achieved independently of division and does not appear to be
      dictated by the pole curvature. Instead, evidence suggests that localization of
      PopZ largely relies on PopZ multimerization in chromosome-free regions,
      consistent with a self-organizing mechanism.

PMID- 18805090
TI  - Mechanism of replication-coupled DNA interstrand crosslink repair.
AB  - DNA interstrand crosslinks (ICLs) are toxic DNA lesions whose repair occurs in
      the S phase of metazoans via an unknown mechanism. Here, we describe a cell-free
      system based on Xenopus egg extracts that supports ICL repair. During DNA
      replication of a plasmid containing a site-specific ICL, two replication forks
      converge on the crosslink. Subsequent lesion bypass involves advance of a nascent
      leading strand to within one nucleotide of the ICL, followed by incisions,
      translesion DNA synthesis, and extension of the nascent strand beyond the lesion.
      Immunodepletion experiments suggest that extension requires DNA polymerase zeta.
      Ultimately, a significant portion of the input DNA is fully repaired, but not if
      DNA replication is blocked. Our experiments establish a mechanism for ICL repair
      that reveals how this process is coupled to DNA replication.

PMID- 18805091
TI  - Sgs1 helicase and two nucleases Dna2 and Exo1 resect DNA double-strand break
      ends.
AB  - Formation of single-strand DNA (ssDNA) tails at a double-strand break (DSB) is a
      key step in homologous recombination and DNA-damage signaling. The enzyme(s)
      producing ssDNA at DSBs in eukaryotes remain unknown. We monitored 5'-strand
      resection at inducible DSB ends in yeast and identified proteins required for two
      stages of resection: initiation and long-range 5'-strand resection. We show that
      the Mre11-Rad50-Xrs2 complex (MRX) initiates 5' degradation, whereas Sgs1 and
      Dna2 degrade 5' strands exposing long 3' strands. Deletion of SGS1 or DNA2
      reduces resection and DSB repair by single-strand annealing between distant
      repeats while the remaining long-range resection activity depends on the
      exonuclease Exo1. In exo1Deltasgs1Delta double mutants, the MRX complex together
      with Sae2 nuclease generate, in a stepwise manner, only few hundred nucleotides
      of ssDNA at the break, resulting in inefficient gene conversion and G2/M damage
      checkpoint arrest. These results provide important insights into the early steps
      of DSB repair in eukaryotes.

PMID- 18805092
TI  - Structural insights into NEDD8 activation of cullin-RING ligases: conformational
      control of conjugation.
AB  - Cullin-RING ligases (CRLs) comprise the largest ubiquitin E3 subclass, in which a
      central cullin subunit links a substrate-binding adaptor with an E2-binding RING.
      Covalent attachment of the ubiquitin-like protein NEDD8 to a conserved C-terminal
      domain (ctd) lysine stimulates CRL ubiquitination activity and prevents binding
      of the inhibitor CAND1. Here we report striking conformational rearrangements in
      the crystal structure of NEDD8~Cul5(ctd)-Rbx1 and SAXS analysis of
      NEDD8~Cul1(ctd)-Rbx1 relative to their unmodified counterparts. In NEDD8ylated
      CRL structures, the cullin WHB and Rbx1 RING subdomains are dramatically
      reoriented, eliminating a CAND1-binding site and imparting multiple potential
      catalytic geometries to an associated E2. Biochemical analyses indicate that the
      structural malleability is important for both CRL NEDD8ylation and subsequent
      ubiquitination activities. Thus, our results point to a conformational control of
      CRL activity, with ligation of NEDD8 shifting equilibria to disfavor inactive
      CAND1-bound closed architectures, and favor dynamic, open forms that promote
      polyubiquitination.

PMID- 18805093
TI  - A double S shape provides the structural basis for the extraordinary binding
      specificity of Dscam isoforms.
AB  - Drosophila Dscam encodes a vast family of immunoglobulin (Ig)-containing proteins
      that exhibit isoform-specific homophilic binding. This diversity is essential for
      cell recognition events required for wiring the brain. Each isoform binds to
      itself but rarely to other isoforms. Specificity is determined by "matching" of
      three variable Ig domains within an approximately 220 kD ectodomain. Here, we
      present the structure of the homophilic binding region of Dscam, comprising the
      eight N-terminal Ig domains (Dscam(1-8)). Dscam(1-8) forms a symmetric homodimer
      of S-shaped molecules. This conformation, comprising two reverse turns, allows
      each pair of the three variable domains to "match" in an antiparallel fashion.
      Structural, genetic, and biochemical studies demonstrate that, in addition to
      variable domain "matching," intramolecular interactions between constant domains
      promote homophilic binding. These studies provide insight into how "matching" at
      all three pairs of variable domains in Dscam mediates isoform-specific
      recognition.

PMID- 18805094
TI  - Expression cloning of TMEM16A as a calcium-activated chloride channel subunit.
AB  - Calcium-activated chloride channels (CaCCs) are major regulators of sensory
      transduction, epithelial secretion, and smooth muscle contraction. Other crucial
      roles of CaCCs include action potential generation in Characean algae and
      prevention of polyspermia in frog egg membrane. None of the known molecular
      candidates share properties characteristic of most CaCCs in native cells. Using
      Axolotl oocytes as an expression system, we have identified TMEM16A as the
      Xenopus oocyte CaCC. The TMEM16 family of "transmembrane proteins with unknown
      function" is conserved among eukaryotes, with family members linked to
      tracheomalacia (mouse TMEM16A), gnathodiaphyseal dysplasia (human TMEM16E),
      aberrant X segregation (a Drosophila TMEM16 family member), and increased sodium
      tolerance (yeast TMEM16). Moreover, mouse TMEM16A and TMEM16B yield CaCCs in
      Axolotl oocytes and mammalian HEK293 cells and recapitulate the broad CaCC
      expression. The identification of this new family of ion channels may help the
      development of CaCC modulators for treating diseases including hypertension and
      cystic fibrosis.

PMID- 18805095
TI  - Intramolecular strain coordinates kinesin stepping behavior along microtubules.
AB  - Kinesin advances 8 nm along a microtubule per ATP hydrolyzed, but the mechanism
      responsible for coordinating the enzymatic cycles of kinesin's two identical
      motor domains remains unresolved. Here, we have tested whether such coordination
      is mediated by intramolecular tension generated by the "neck linkers," mechanical
      elements that span between the motor domains. When tension is reduced by
      extending the neck linkers with artificial peptides, the coupling between ATP
      hydrolysis and forward stepping is impaired and motor's velocity decreases as a
      consequence. However, speed recovers to nearly normal levels when external
      tension is applied by an optical trap. Remarkably, external load also induces
      bidirectional stepping of an immotile kinesin that lacks its mechanical element
      (neck linker) and fuel (ATP). Our results indicate that the kinesin motor domain
      senses and responds to strain in a manner that facilitates its plus-end-directed
      stepping and communication between its two motor domains.

PMID- 18805096
TI  - The fragile X syndrome protein represses activity-dependent translation through
      CYFIP1, a new 4E-BP.
AB  - Strong evidence indicates that regulated mRNA translation in neuronal dendrites
      underlies synaptic plasticity and brain development. The fragile X mental
      retardation protein (FMRP) is involved in this process; here, we show that it
      acts by inhibiting translation initiation. A binding partner of FMRP,
      CYFIP1/Sra1, directly binds the translation initiation factor eIF4E through a
      domain that is structurally related to those present in 4E-BP translational
      inhibitors. Brain cytoplasmic RNA 1 (BC1), another FMRP binding partner,
      increases the affinity of FMRP for the CYFIP1-eIF4E complex in the brain. Levels
      of proteins encoded by known FMRP target mRNAs are increased upon reduction of
      CYFIP1 in neurons. Translational repression is regulated in an activity-dependent
      manner because BDNF or DHPG stimulation of neurons causes CYFIP1 to dissociate
      from eIF4E at synapses, thereby resulting in protein synthesis. Thus, the
      translational repression activity of FMRP in the brain is mediated, at least in
      part, by CYFIP1.

PMID- 18805097
TI  - Regulation of neurogenesis by interkinetic nuclear migration through an apical
      basal notch gradient.
AB  - The different cell types in the central nervous system develop from a common pool
      of progenitor cells. The nuclei of progenitors move between the apical and basal
      surfaces of the neuroepithelium in phase with their cell cycle, a process termed
      interkinetic nuclear migration (INM). In the retina of zebrafish mikre oko (mok)
      mutants, in which the motor protein Dynactin-1 is disrupted, interkinetic nuclei
      migrate more rapidly and deeply to the basal side and more slowly to the apical
      side. We found that Notch signaling is predominantly activated on the apical side
      in both mutants and wild-type. Mutant progenitors are, thus, less exposed to
      Notch and exit the cell cycle prematurely. This leads to an overproduction of
      early-born retinal ganglion cells (RGCs) at the expense of later-born
      interneurons and glia. Our data indicate that the function of INM is to balance
      the exposure of progenitor nuclei to neurogenic versus proliferative signals.

PMID- 18805098
TI  - Probing nucleosome function: a highly versatile library of synthetic histone H3
      and H4 mutants.
AB  - Nucleosome structural integrity underlies the regulation of DNA metabolism and
      transcription. Using a synthetic approach, a versatile library of 486 systematic
      histone H3 and H4 substitution and deletion mutants that probes the contribution
      of each residue to nucleosome function was generated in Saccharomyces cerevisiae.
      We probed fitness contributions of each residue to perturbations of chromosome
      integrity and transcription, mapping global patterns of chemical sensitivities
      and requirements for transcriptional silencing onto the nucleosome surface. Each
      histone mutant was tagged with unique molecular barcodes, facilitating
      identification of histone mutant pools through barcode amplification, labeling,
      and TAG microarray hybridization. Barcodes were used to score complex phenotypes
      such as competitive fitness in a chemostat, DNA repair proficiency, and synthetic
      genetic interactions, revealing new functions for distinct histone residues and
      new interdependencies among nucleosome components and their modifiers.

PMID- 18805099
TI  - SnapShot: Ca(2+)-dependent transcription in neurons.

PMID- 18805100
TI  - Association between serum uric acid and perioperative and late cardiovascular
      outcome in patients with suspected or definite coronary artery disease undergoing
      elective vascular surgery.
AB  - The role of uric acid as an independent marker of cardiovascular risk is unclear.
      Therefore, our aim was to assess the independent contribution of preoperative
      serum uric acid levels to the risk of 30-day and late mortality and major adverse
      cardiac event (MACE) in patients scheduled for open vascular surgery. In total,
      936 patients (76% male, age 68 +/- 11 years) were enrolled. Hyperuricemia was
      defined as serum uric acid >0.42 mmol/l for men and >0.36 mmol/l for women, as
      defined by large epidemiological studies. Outcome measures were 30-day and late
      mortality and MACE (cardiac death or myocardial infarction). Multivariable
      logistic and Cox regression analysis were used, adjusting for age, gender, and
      all cardiac risk factors. Data are presented as odds ratios or hazard ratios,
      with 95% confidence intervals. Hyperuricemia was present in 299 patients (32%).
      The presence of hyperuricemia was associated with heart failure, chronic kidney
      disease, and the use of diuretics. Perioperatively, 46 patients (5%) died and 61
      patients (7%) experienced a MACE. Mean follow-up was 3.7 years (range: 0 to 17
      years). During follow-up, 282 patients (30%) died and 170 patients (18%)
      experienced a MACE. After adjustment for all clinical risk factors, the presence
      of hyperuricemia was not significantly associated with an increased risk of 30
      day mortality or MACE, odds ratios of 1.5 (0.8 to 2.8) and 1.7 (0.9 to 3.0),
      respectively. However, the presence of hyperuricemia was associated with an
      increased risk of late mortality and MACE, with hazard ratios of 1.4 (1.1 to 1.7)
      and 1.7 (1.3 to 2.3), respectively. In conclusion, the presence of preoperative
      hyperuricemia in vascular patients is a significant predictor of late mortality
      and MACE.

PMID- 18805101
TI  - Disparities in use of same-day percutaneous coronary intervention for patients
      with ST-elevation myocardial infarction in Florida, 2001-2005.
AB  - Primary percutaneous coronary intervention (PCI) is the recommended treatment for
      ST-elevation myocardial infarction (STEMI), according to American College of
      Cardiology and American Heart Association guidelines published in 1999 and 2004.
      In this study, hospital and patient predictors of same-day primary PCI use for
      STEMI were examined across the period from 2001 to 2005. Inpatient discharge data
      for adults aged > or =18 years with primary diagnoses of STEMI who were admitted
      to Florida hospitals through emergency departments (ED) from 2001 to 2005 (n =
      58,308) were analyzed. Hierarchical (multilevel) logistic regression models were
      used to assess hospital PCI volume and individual characteristics as predictors
      of same-day PCI use for patients at PCI-capable hospitals. The percentage of ED
      admitted patients with a STEMI who received same-day PCI in Florida increased
      from 20% in early 2001 to 43% in late 2005. At PCI-capable hospitals, 50% of
      these patients received same-day PCI in late 2005. Patients admitted on weekends,
      women, patients aged > or = 75 years, patients with chronic obstructive pulmonary
      disease, and patients with end-stage renal disease were all significantly less
      likely to receive same-day PCI. Black patients were less likely to receive same
      day PCI in early 2001 (adjusted odds ratio [OR] 0.7, 95% confidence interval 0.5
      to 0.9, p <0.0001), but this racial disparity was not evident by late 2005
      (adjusted OR 1.0). Men were more likely than women to receive same-day PCI, with
      a significant association remaining in late 2005 (adjusted OR 1.2, 95% confidence
      interval 1.1 to 1.4, p <0.0001). Throughout the study period, the strongest
      predictor of same-day PCI was admission to a high- or medium-volume PCI-capable
      hospital; the adjusted OR in late 2005 was 4.6 (95% confidence interval 2.8 to
      7.6, p <0.0001). In conclusion, weekend admission, female gender, older age, and
      serious co-morbidities were all significant barriers to receiving same-day PCI.
      Among patients admitted to PCI-capable hospitals, total PCI volume (high or
      medium vs low) was associated with significantly greater odds of receiving
      primary PCI, independent of patient sociodemographics, risk factors, or co
      morbidities. Statewide, despite an increase in the use of PCI over time, most ED
      admitted patients with a STEMI in Florida did not receive primary PCI in late
      2005.

PMID- 18805102
TI  - Usefulness of revascularization of patients with multivessel coronary artery
      disease before elective vascular surgery for abdominal aortic and peripheral
      occlusive disease.
AB  - The Coronary Artery Revascularization Prophylaxis (CARP) study showed no survival
      benefit with preoperative coronary artery revascularization before elective
      vascular surgery. The generalizability of the trial results to all patients with
      multivessel coronary artery disease (CAD) has been questioned. The objective of
      this study was to determine the impact of prophylactic coronary revascularization
      on long-term survival in patients with multivessel CAD. Over a 4-year period,
      1,048 patients underwent coronary angiography before vascular surgery during
      screening into the CARP trial. The cohort was composed of registry (n = 586) and
      randomized (n = 462) patients, and their survival was determined at 2.5 years
      after vascular surgery. High-risk coronary anatomy without previous bypass
      surgery included 2-vessel disease (n = 204 [19.5%]), 3-vessel disease (n = 130
      [12.4%]), and left main coronary artery stenosis > or = 50% (n = 48 [4.6%]). By
      log-rank test, preoperative revascularization was associated with improved
      survival in patients with a left main coronary artery stenoses (0.84 vs 0.52, p
      <0.01) but not those with either 2-vessel (0.80 vs 0.79, p = 0.83) or 3-vessel
      (0.79 vs 0.71, p = 0.15) disease. In conclusion, unprotected left main coronary
      artery disease was present in 4.6% of patients who underwent coronary angiography
      before vascular surgery, and this was the only subset of patients showing a
      benefit with preoperative coronary artery revascularization.

PMID- 18805103
TI  - Usefulness of routine periodic fasting to lower risk of coronary artery disease
      in patients undergoing coronary angiography.
AB  - Coronary artery disease (CAD) is common and multifactorial. Members of the Church
      of Jesus Christ of Latter-day Saints (LDS, or Mormons) in Utah may have lower
      cardiac mortality than other Utahns and the US population. Although the LDS
      proscription of smoking likely contributes to lower cardiac risk, it is unknown
      whether other shared behaviors also contribute. This study evaluated potential
      CAD-associated effects of fasting. Patients (n(1) = 4,629) enrolled in the
      Intermountain Heart Collaborative Study registry (1994 to 2002) were evaluated
      for the association of religious preference with CAD diagnosis (> or = 70%
      coronary stenosis using angiography) or no CAD (normal coronaries, <10%
      stenosis). Consequently, another set of patients (n(2) = 448) were surveyed (2004
      to 2006) for the association of behavioral factors with CAD, with routine fasting
      (i.e., abstinence from food and drink) as the primary variable. Secondary survey
      measures included proscription of alcohol, tea, and coffee; social support; and
      religious worship patterns. In population 1 (initial), 61% of LDS and 66% of all
      others had CAD (adjusted [including for smoking] odds ratio [OR] 0.81, p =
      0.009). In population 2 (survey), fasting was associated with lower risk of CAD
      (64% vs 76% CAD; OR 0.55, 95% confidence interval 0.35 to 0.87, p = 0.010), and
      this remained after adjustment for traditional risk factors (OR 0.46, 95%
      confidence interval 0.27 to 0.81, p = 0.007). Fasting was also associated with
      lower diabetes prevalence (p = 0.048). In regression models entering other
      secondary behavioral measures, fasting remained significant with a similar effect
      size. In conclusion, not only proscription of tobacco, but also routine periodic
      fasting was associated with lower risk of CAD.

PMID- 18805104
TI  - Predictors of endothelial function in employees with sedentary occupations in a
      worksite exercise program.
AB  - A sedentary workforce may be at increased risk for future cardiovascular disease.
      Exercise at the work site has been advocated, but effects on endothelium as a
      biomarker of risk and relation to weight loss, lipid changes, or circulating
      endothelial progenitor cells (EPCs) have not been reported. Seventy-two office
      and laboratory employees (58 women; average age 45 years, range 22 to 62; 26 with
      body mass index values >30 kg/m(2)) completed 3 months of participation in the
      National Heart, Lung, and Blood Institute's Keep the Beat program, with the
      determination of vital signs, laboratory data, and peak oxygen consumption
      (VO(2)) during treadmill exercise. Brachial artery endothelium was tested by flow
      mediated dilation (FMD), which at baseline was inversely associated with
      Framingham risk score (r = -0.3689, p <0.0001). EPCs were quantified by colony
      assay. With exercise averaging 98 +/- 47 minutes each workweek, there was
      improvement in FMD (from 7.8 +/- 3.4% to 8.5 +/- 3.0%, p = 0.0096) and peak VO(2)
      (+1.2 +/- 3.1 ml O(2)/kg/min, p = 0.0028), with reductions in diastolic blood
      pressure (-2 +/- 8 mm Hg, p = 0.0478), total cholesterol (-8 +/- 25 mg/dl, p =
      0.0131), and low-density lipoprotein cholesterol (-7 +/- 19 mg/dl, p = 0.0044)
      but with a marginal reduction in weight (-0.5 +/- 2.1 kg, p = 0.0565). By
      multiple regression modeling, lower baseline FMD, greater age, reductions in
      total and low-density lipoprotein cholesterol and diastolic blood pressure, and
      increases in EPC colonies and peak VO(2) were jointly statistically significant
      predictors of change in FMD and accounted for 47% of the variability in FMD
      improvement with program participation. Results were similar when modeling was
      performed for women only. In contrast, neither adiposity at baseline nor change
      in weight was a predictor of improved endothelial function. In conclusion, daily
      exercise achievable at their work sites by employees with sedentary occupations
      improves endothelial function, even with the absence of weight loss, which may
      decrease cardiovascular risk, if sustained.

PMID- 18805105
TI  - Relation of Framingham risk score to subclinical atherosclerosis evaluated across
      three arterial sites.
AB  - The Framingham risk score (FRS) is widely used in clinical practice to identify
      subjects at high risk for developing coronary heart disease. However, FRS may not
      accurately identify subjects at risk. We measured subclinical atherosclerosis in
      the coronary arteries and aorta with the presence of calcium and in the common
      carotid artery by intima-media thickness in 498 healthy subjects. The
      distribution of these subclinical atherosclerosis measures was evaluated across 3
      strata of the FRS. Coronary arteries with the presence of calcium, aorta with the
      presence of calcium, and carotid artery by intima-media thickness were
      significantly independently associated with FRS. The FRS increased with the
      number of arterial sites with atherosclerosis; 69% of the subjects categorized in
      the low risk group (FRS <10%), 95% of the intermediate risk group (FRS 10% to
      20%), and 100% of the high risk group (FRS >20%) had > or = 1 vascular imaging
      studies demonstrating subclinical atherosclerosis. In the low risk group,
      subjects with atherosclerosis had a longer history of lifetime smoking compared
      with those without atherosclerosis. In conclusion, subclinical atherosclerosis is
      prominent across the spectrum of FRS. Evaluation of subclinical atherosclerosis
      in different arterial sites in addition to FRS may be useful in targeting
      subjects for lifestyle and other interventions.

PMID- 18805106
TI  - Usefulness of fasting plasma glucose to predict mortality or coronary heart
      disease in persons > or = 60 years of age without diabetes mellitus or in those
      with undiagnosed diabetes mellitus (from The Dubbo Study).
AB  - The role of fasting plasma glucose (FPG) levels below diabetes "thresholds" in
      predicting mortality or coronary heart disease (CHD) is unclear. This study
      examines whether FPG predicts mortality or CHD in subjects without diabetes
      (historical or undiagnosed) or in those with undiagnosed diabetes (or lesser
      degrees of glucose intolerance). We have analyzed all-causes mortality and CHD
      incidence from a 16-year follow-up in a cohort of Australian senior citizens, 60
      years and older, first examined in 1988-89. Diabetes was defined on historical
      grounds or by use of medication; undiagnosed diabetics were those without history
      but with FPG >124 mg/dl. Hazard ratio and 95% confidence intervals of the
      specified outcomes were obtained from Cox models, with FPG being entered as a
      continuous variable. Mortality and CHD incidence rates in subjects with previous
      cardiovascular disease (CVD) and diabetes were substantially higher than in
      nondiabetics, but CHD rates were disproportionately higher in diabetic women. FPG
      did not significantly predict any outcome in men in the absence of diabetes. In
      women, FPG was a significant predictor of death (hazard ratio = 1.30, 95%
      confidence interval 1.09 to 1.56) and CHD (hazard ratio 1.24, confidence interval
      1.02 to 1.51) in the cohort, which included previous CVD but excluded all
      diabetes. In women with undiagnosed diabetes, FPG predicted death independently
      of previous CVD presence but did not predict CHD. In conclusion, FPG in the range
      of 95 to 108 mg/dl in a nondiabetic woman is still of prognostic importance for
      survival or CHD if she has previous CVD, whereas FPG is of prognostic importance
      for survival if she has undiagnosed diabetes. No similar findings were made in
      men.

PMID- 18805107
TI  - Epidemiology, heritability, and genetic linkage of C-reactive protein in African
      Americans (from the Jackson Heart Study).
AB  - C-reactive protein (CRP) has been studied largely in white non-Hispanic cohorts.
      There is limited information on CRP's range of values, heritability, and relation
      to cardiovascular disease risk factors in African Americans. The aim of this
      study was to evaluate the distribution, clinical correlates, heritability, and
      genetic linkage of log-transformed CRP in participants in the middle-aged to
      elderly African American cohort in the community-based Jackson Heart Study. The
      distribution and correlates of CRP were analyzed for the entire study cohort who
      underwent the first examination (2001 to 2004). Heritability was estimated for
      the family cohort nested within the larger Jackson Heart Study (246 families, n =
      1,317). The relation between CRP and cardiovascular disease risk factors was
      tested with multivariable stepwise regression analyses. Heritability was
      estimated using a variance-components method. Linkage analysis was performed
      using the multipoint variance-components approach. The study sample consisted of
      4,919 participants (mean age 55 +/- 13 years, 63% women); the median CRP
      concentration was 2.7 mg/L. In stepwise models, traditional risk factors
      explained 23.8% of CRP's variability, with body mass index (partial R(2) = 13.6%)
      explaining 57.1% of the variability of CRP due to traditional risk factors. The
      heritability of CRP (adjusted for age, gender, and body mass index) was 0.45. The
      strongest linkage evidence for CRP was observed on chromosome 11 (11p13 to
      11p11.2), with a logarithm of odds score of 2.72. In conclusion, in this large
      population-based cohort of African Americans, circulating CRP concentration was
      heritable and associated with several traditional cardiovascular risk factors,
      particularly body mass index.

PMID- 18805108
TI  - Comparison of anticoagulant and anti-inflammatory responses using enoxaparin
      versus unfractionated heparin for transesophageal echocardiography-guided
      cardioversion of atrial fibrillation.
AB  - The Assessment of Cardioversion Using Transesophageal Echocardiography (ACUTE) II
      study compared enoxaparin with unfractionated heparin (UFH) as bridging therapy
      in patients with atrial fibrillation >2 days in duration who underwent
      transesophageal echocardiography-guided cardioversion. In the present study, the
      anticoagulant and anti-inflammatory effects of enoxaparin and UFH were compared
      at prespecified time points. In a randomized substudy of 155 patients from 17
      clinical sites, the anticoagulant activity of enoxaparin (n = 76) was compared
      with that of UFH (n = 79). Blood samples were drawn at enrollment, on day 2, and
      on day 4 in the 2 groups. Blood samples were evaluated for anticoagulant activity
      by measuring the activated partial thromboplastin time, anti-Xa, anti-IIa, and
      tissue factor pathway inhibitor levels. In addition, levels of coagulation
      activation (by thrombin antithrombin complex) and inflammation (by highly
      sensitive C-reactive protein) were measured. The results of this substudy showed
      that the anti-Xa levels in the 2 groups increased on day 2. Similar increases in
      anti-Xa were observed on day 4. The anti-Xa levels and tissue factor pathway
      inhibitor levels were higher in the enoxaparin group compared with the UFH group
      on days 2 and 4. However, as expected, the anti-IIa levels in the UFH group were
      higher. In addition, markers of coagulation activation and inflammation were
      increased in patients with atrial fibrillation. Treatment with enoxaparin
      significantly decreased thrombin antithrombin complex levels compared with
      treatment with UFH. Highly sensitive C-reactive protein levels were also
      decreased after treatment in the 2 groups. In conclusion, the ACUTE II study
      showed that the use of enoxaparin for bridging therapy in patients with atrial
      fibrillation who underwent transesophageal echocardiography-guided cardioversion
      resulted in a more predictable and stronger anticoagulant response than that
      observed with UFH. Markers of inflammation were also decreased in the 2 groups.

PMID- 18805109
TI  - Comparison of left atrial volumes and function by real-time three-dimensional
      echocardiography in patients having catheter ablation for atrial fibrillation
      with persistence of sinus rhythm versus recurrent atrial fibrillation three
      months later.
AB  - Real-time 3-dimensional echocardiography (RT3DE) can provide a unique combination
      of accurate left atrial (LA) volume quantification and rapid, automatic
      assessment of LA function. The aim of the study was to evaluate the changes in LA
      volumes and function in patients with atrial fibrillation (AF) undergoing
      radiofrequency catheter ablation (RFCA) using RT3DE; 57 consecutive patients
      referred for RFCA were studied. Paroxysmal AF was present in 43 patients (75%)
      and persistent AF in 14 (25%). After a mean follow-up of 7.9 +/- 2.7 months,
      patients were divided into 2 groups: successful RFCA (SR group) and recurrence of
      AF (AF group). RT3DE was performed before, within 3 days, and 3 months after RFCA
      to assess LA volumes (maximum, minimum, and preA) and LA functions (passive,
      active, and reservoir). A total of 38 patients (67%) had successful RFCA (SR
      group). Immediately after RFCA, no significant changes in LA volumes and function
      were observed. After 3 months, a significant reduction in LA volumes (maximum: 26
      +/- 8 to 23 +/- 7 ml/m(2), p <0.01) was noted only in the SR group, with a
      significant improvement in LA active (22 +/- 8% to 33 +/- 9%, p <0.01) and
      reservoir functions (116 +/- 45% to 152 +/- 54%, p <0.01). Conversely, the AF
      group showed a trend towards a deterioration of LA volumes and function. In
      conclusion, in patients who maintain sinus rhythm after RFCA, a significant
      reverse remodeling and functional improvement of the left atrium is observed
      using RT3DE.

PMID- 18805110
TI  - Usefulness of echo-guided cardiac resynchronization pacing in patients undergoing
      "ablate and pace" therapy for permanent atrial fibrillation and effects of heart
      rate regularization and left ventricular resynchronization.
AB  - An acute comparative study of right ventricular (RV) pacing and
      echocardiographically guided cardiac resynchronization pacing (CRP) was performed
      in patients who underwent "ablate and pace" therapy for permanent atrial
      fibrillation. It was hypothesized that optimized CRP guided by tissue Doppler
      echocardiography would exert an additive beneficial hemodynamic effect to that of
      rate regularization achieved through atrioventricular junction ablation. An acute
      intrapatient comparison of echocardiographic parameters was performed between
      baseline preablation values and RV pacing and CRP (performed <24 hours after
      ablation) in 50 patients. Optimized CRP configuration was defined as the modality
      of pacing corresponding to that of the shortest intra-left ventricular (LV) delay
      among simultaneous biventricular pacing, sequential biventricular pacing, and
      single-chamber pacing. The intra-LV delay was defined as the difference between
      the longest and the shortest activation time in the six basal segments of the
      left ventricle. Compared with preablation measures, the ejection fraction
      increased by 10.8% during RV pacing (19% in patients with intra-LV delays <47.5
      ms and 3% in those with intra-LV delays >47.5 ms). Compared with RV pacing, CRP
      caused a 9.2% increase in the ejection fraction, a 6.8% decrease in LV systolic
      diameter, and a 17.3% decrease in mitral regurgitation area; LV dyssynchrony was
      reduced from 52 +/- 27 to 21 +/- 12 ms. Similar results were observed in patients
      with and without depressed systolic function and in patients with and without
      left bundle branch block. In conclusion, rate regularization achieved through
      atrioventricular junction ablation and RV pacing provides a favorable hemodynamic
      effect that is inversely related to the level of LV dyssynchrony. Minimizing LV
      dyssynchrony by means of optimized CRP yields an additional important benefit.

PMID- 18805111
TI  - Increased inflammatory cell infiltration in the atrial myocardium of patients
      with atrial fibrillation.
AB  - Atrial fibrillation (AF) may be caused by structural and electrophysiological
      changes in the atria induced by inflammation. This study analyzed 35 adult
      patients with symptomatic severe mitral valve disease and moderate-to-severe
      tricuspid valve disease and without coronary artery disease who underwent valve
      operations for congestive heart failure; 18 patients had persistent AF and 17
      patients had no history or electrocardiogram examination of AF before surgery.
      Atrial appendageal tissues obtained during surgery were evaluated for
      histopathological changes. The number of inflammatory cells identified as CD45
      positive cells in the right atrial myocardium in the AF group (7.5 +/- 7.5 cells
      per high power field) was significantly higher than that of normal controls (2.7
      +/- 1.5 cells per high power field, p = 0.0018). The number of inflammatory cells
      in the right atrial myocardium did not differ between the sinus group and normal
      controls (2.7 +/- 1.5 vs 2.6 +/- 2.2 cells per high power field, p >0.05).
      Additionally, the number of inflammatory cells in the atrial myocardium did not
      differ between the right and left atria in patients with AF (7.5 +/- 7.5 cells
      per high power field for right atria vs 7.1 +/- 4.2 cells per high power field
      for left atria, p = 0.7563). Moreover, correlation analysis revealed a
      significant association between the number of inflammatory cells in the right
      atrial myocardium and the number of inflammatory cells in the left atrial
      myocardium in patients with AF (r = 0.6145, p = 0.0067). In conclusion,
      inflammatory cell infiltration increases in the atrial myocardium of patients
      with AF.

PMID- 18805112
TI  - Differences in treadmill exercise tolerance parameters between patients with
      partial and advanced interatrial depolarization abnormality.
AB  - Advanced interatrial block (aIAB) is considerably much less common than partial
      interatrial block (pIAB), occuring in <2% of the elderly hospitalized population.
      Less is, therefore, known of the true clinical burden of aIAB, particularly in
      relation to graded exercise. Therefore, 12 patients with aIAB and 30 patients
      with pIAB who performed a baseline exercise tolerance test and had a repeat test
      performed > or = 2 years later were included in the study. Exercise tolerance,
      echocardiographic findings, and major adverse cardiovascular events were
      compared. Left atrial size progressed at a significantly faster rate in those
      with aIAB. In addition, Duke Prognostic Treadmill scores were significantly lower
      on follow-up in those patients with aIAB. Overall, patients with aIAB had
      significantly greater left atrial size (48.3 +/- 9 vs 42.8 +/- 4 mm, p < 0.01)
      and significantly lower Duke Prognostic Treadmill scores than those with pIAB (
      0.2 +/- 5 vs 4.1 +/- 4, p < 0.05). There were, however, no significant
      differences in the occurence of major adverse cardiovascular events. In
      conclusion, left atrial size progressed at a significantly faster rate but Duke
      Prognostic Treadmill scores were significantly lower in those with aIAB compared
      with patients with pIAB after > or = 2 years of follow-up. Further study is
      required to determine whether patients with aIAB require follow-up
      echocardiography and/or exercise tolerance tests for optimal risk stratification.

PMID- 18805114
TI  - Managed ventricular pacing in pediatric patients and patients with congenital
      heart disease.
AB  - Ventricular dyssynchrony induced by ventricular pacing (VP) may predispose
      patients to congestive heart failure. The detrimental effects of VP are directly
      related to the cumulative percentage of VP (Cum%VP). Managed VP (MVP) is a novel
      pacing algorithm developed to minimize unnecessary VP by uncoupling atrial pacing
      from VP. This retrospective analysis assessed the feasibility of using MVP in
      pediatric patients and patients with congenital heart disease (CHD). A
      multicenter review evaluated all pediatric patients <22 years old and older
      patients with CHD that had an implanted device using a MVP algorithm. Primary
      outcome variables were Cum%VP and adverse events. A subgroup analysis evaluated
      patients that had a DDD(R) pacemaker before a MVP device and compared Cum%VP
      before and after initiation of MVP. From 6 centers 62 patients (mean age 21.5 +/-
      9.6 years) were included; 64% had CHD. With a MVP device, mean Cum%VP was 4.3 +/-
      14.6% (range 0 to 83.7): Eleven patients were eligible for subgroup analysis.
      Compared with DDD(R), Cum%VP significantly decreased with MVP (67.1 +/- 29.4% vs
      9.2 +/- 24.8%, p = 0.002). One MVP-related adverse event occurred; a patient with
      intermittent atrioventricular block had symptoms with frequent nonconducted
      atrial depolarizations and was reprogrammed to DDD. In conclusion, MVP can be
      used safely and can significantly reduce unnecessary VP in pediatric patients and
      patients with CHD.

PMID- 18805113
TI  - Risk of cardiac events in patients with asthma and long-QT syndrome treated with
      beta(2) agonists.
AB  - The clinical course and risk factors associated with beta(2)-agonist therapy for
      asthma have not been investigated previously in patients with the long-QT
      syndrome (LQTS). The risk of a first LQTS-related cardiac event due to beta(2)
      agonist therapy was examined in 3,287 patients enrolled in the International LQTS
      Registry with QTc > or = 450 ms. The Cox proportional hazards model was used to
      assess the independent contribution of clinical factors for first cardiac events
      (syncope, aborted cardiac arrest, or sudden death) from birth through age 40.
      Time-dependent beta(2)-agonist therapy for asthma was associated with an
      increased risk for cardiac events (hazard ratio [HR] = 2.00, 95% confidence
      interval 1.26 to 3.15, p = 0.003) after adjustment for relevant covariates
      including time-dependent beta-blocker use, gender, QTc, and history of asthma.
      This risk was augmented within the first year after the initiation of beta(2)
      agonist therapy (HR = 3.53, p = 0.006). The combined use of beta(2)-agonist
      therapy and anti-inflammatory steroids was associated with an elevated risk for
      cardiac events (HR = 3.66, p <0.01); beta-blocker therapy was associated with a
      reduction in cardiac events in those using beta(2) agonists (HR = 0.14, p =
      0.05). In conclusion, beta(2)-agonist therapy was associated with an increased
      risk for cardiac events in patients with asthma with LQTS, and this risk was
      diminished in patients receiving beta blockers.

PMID- 18805115
TI  - Prognostic usefulness of dyspnea versus fatigue as reason for exercise test
      termination in patients with heart failure.
AB  - Cardiopulmonary exercise testing (CPX) is an integral tool for assessing the
      clinical status and prognosis of patients with heart failure (HF). The present
      investigation examined differences in CPX variables and prognosis according to
      reason for test termination. One hundred eighty-three patients with HF (69% men,
      31% women; mean age 53 +/- 13 years, left ventricular ejection fraction at rest
      24.3 +/- 9.9%) underwent CPX in which the minute ventilation/carbon dioxide
      production slope, peak oxygen consumption, and peak respiratory exchange ratio
      were determined. Subjects were tracked for cardiac-related events for 2 years
      after CPX. Dyspnea and fatigue (general fatigue/leg fatigue) were the primary
      reasons for test termination in 79 and 104 patients, respectively. Peak oxygen
      consumption (15.4 +/- 5.7 vs 17.5 +/- 5.9 ml o(2) . kg(-1) . min(-1)) was
      significantly lower, whereas minute ventilation/carbon dioxide production slope
      (38.5 +/- 12.8 vs 33.9 +/- 9.8) was significantly higher in the dyspnea subgroup
      (p <0.05). There were 41 cardiac-related events during the 2-year tracking
      period. Patients with dyspnea were at significantly higher risk of adverse events
      (hazard ratio 2.1, 95% confidence interval 1.1 to 4.0, p = 0.02). In conclusion,
      these results indicate that patients with HF terminating an exercise test
      primarily because of dyspnea have an increased incidence of cardiac-related
      events and poorer CPX markers than those limited by fatigue.

PMID- 18805116
TI  - Perioperative bridging therapy with unfractionated heparin or low-molecular
      weight heparin in patients with mechanical prosthetic heart valves on long-term
      oral anticoagulants (from the REGIMEN Registry).
AB  - Patients with mechanical prosthetic heart valves require long-term oral
      anticoagulant therapy (OAT). During the temporary interruption of OAT, bridging
      anticoagulant therapy with unfractionated heparin (UFH) or low-molecular-weight
      heparin (LMWH) is recommended. This prespecified subgroup analysis from REGIMEN-a
      large, prospective, multicenter registry-compared UFH (n = 73) and LMWH (n = 172)
      as bridging anticoagulation in patients with mechanical heart valves on long-term
      OAT. Patient demographics and co-morbidities were generally similar between
      groups. There were more bileaflet valves in the LMWH group (67.4% vs 43.8%, p =
      0.0005), but no differences in valve positions between groups. The LMWH group was
      less likely to undergo major surgery (33.7% vs 58.9%, p = 0.0002) and
      cardiothoracic surgery (7.6% vs 19.2%, p = 0.008), and to receive intraprocedural
      anticoagulants or thrombolytics (4.1% vs 13.7%, p = 0.007). Major adverse event
      rates (5.5% vs 10.3%, p = 0.23) and major bleeds (4.2% vs 8.8%, p = 0.17) were
      similar in the LMWH and UFH groups, respectively; 1 arterial thromboembolic event
      occurred in each group. More LMWH-bridged patients were treated as outpatients or
      discharged from the hospital in <24 hours (68.6% vs 6.8%, p <0.0001).
      Multivariate logistic analysis found no significant differences in major bleeds
      and major composite adverse events when adjusting for cardiothoracic or major
      surgery between groups. In conclusion, for patients with mechanical prosthetic
      heart valves on long-term OAT, mostly outpatient-based LMWH bridging therapy
      appears to be feasible for selected procedures, is as safe as UFH, and is
      associated with a low arterial thromboembolic rate.

PMID- 18805117
TI  - Influence of left atrial and ventricular volumes on the relation between mitral
      valve annulus and coronary sinus.
AB  - The aim of this study was to evaluate the anatomic relation between the coronary
      sinus (CS), mitral annulus, and coronary arteries using 64-multislice computed
      tomography (MSCT) in patients presenting with a wide range of atrial volumes and
      left ventricular functions to determine the potential clinical use for
      percutaneous mitral annuloplasty (PMA). The MSCT data of 165 patients (age 63.65
      +/- 12.89 years, 67.3% men) were evaluated. The following variables were
      measured: CS length, CS ostium area, area of the section of CS when it becomes
      great cardiac vein, area between CS and atrioventricular groove assessed in
      volume-rendered 3-dimensional images, axial angle measured as the angle between
      CS and mitral annulus assessed in axial section, mitral valve annulus (MVA) area,
      left atrium volume, and left circumflex artery/marginal branch-CS relation
      referring to mitral annulus. The correlation was inversed between the reduction
      of the axial angle and all following variables: enlargement of both left
      ventricular end-systolic (r = -0.429, p <0.001) and end-diastolic (r = -0.428, p
      <0.001) volumes, left atrial volume (r = -0.361, p <0.001), and MVA (r = -0.324,
      p <0.001). Similarly, there was inverse correlation between the reduction of the
      area between CS and atrioventricular groove, and enlargement of both left
      ventricular end-systolic (r = -0.376, p <0.001) and end-diastolic (r = -0.291, p
      <0.001) volumes, left atrial volume (r = -0.221, p = 0.001), and MVA (r = -0.155,
      p = 0.019). Of note, circumflex artery was located between CS and MVA in 77% of
      the patients, but in patients with severe mitral regurgitation CS crossed
      circumflex/marginal branch artery more frequently (97% of cases). In conclusion,
      a close proximity of the CS to the mitral annulus but also to circumflex artery
      is more likely to occur with left atrial and ventricular enlargement. Thus, MSCT
      should be considered as part of the selection process of potential candidate to
      PMA to avoid external compression of circumflex artery/marginal branch by the
      device.

PMID- 18805118
TI  - Left ventricular systolic and diastolic function in asymptomatic patients with
      moderate aortic stenosis.
AB  - Tissue Doppler imaging (TDI) has improved the ability to detect subclinical
      changes in left ventricular (LV) function. The aim of this study was to
      investigate if asymptomatic patients with moderate aortic stenosis (AS) had
      impaired LV systolic and diastolic function. Fifty patients (mean age 65 +/- 12
      years) recruited into the multicenter Simvastatin + Ezetimibe in Aortic Stenosis
      (SEAS) study with aortic peak velocities of 2.5 and 4.0 m/s were compared with 26
      healthy subjects (mean age 64 +/- 12 years) (p = NS). Peak systolic tissue
      velocities and strain were measured at 8 LV locations and averaged. Early
      diastolic tissue velocity from the septal mitral annulus (E'sep) was measured as
      an index of LV relaxation. The ratio of early diastolic transmitral pulsed
      Doppler (E) to E'sep (E/E'sep) was calculated as an index of LV filling pressure.
      Peak systolic tissue velocity (4.1 +/- 1.0 vs 4.8 +/- 1.1 cm/s, p <0.01) and
      strain (-16.6 +/- 2.7% vs -17.9 +/- 2.0%, p <0.05) were decreased in patients
      with AS compared with controls. E'sep was decreased (4.9 +/- 1.0 vs 5.8 +/- 1.3
      cm/s, p <0.01) and E/E'sep was increased (17.4 +/- 9.7 vs 11.7 +/- 3.8, p <0.01)
      in the AS group compared with the control group. In conclusion, asymptomatic
      patients with moderate AS have impaired LV systolic function as measured by
      reduced peak systolic tissue velocity and strain. Augmented LV filling pressure
      measured by E/E'sep and impaired LV relaxation measured by reduced E'sep also
      indicate diastolic dysfunction in these patients.

PMID- 18805119
TI  - Incidence of atrial fibrillation following transcatheter closure of atrial septal
      defects in adults.
AB  - Transcatheter closure of secundum atrial septal defect (ASD) and patent foramen
      ovale (PFO) has become a routine procedure. Little is known about the effect of
      atrial septal device implantation on the occurrence of atrial fibrillation (AF).
      We evaluated the frequency of AF occurring after transcatheter PFO and ASD
      closure in a large population. From 1994 until 2007 a total of 1,062 patients
      underwent transcatheter closure of an interatrial communication. New-onset AF was
      defined by 12-lead electrocardiogram or Holter monitoring in patients without a
      history of AF at baseline. Of the 1,062 patients, 822 had a PFO and 240 had an
      ASD. During a median follow up of 20 months, new-onset AF was documented in 8% of
      patients. New-onset AF occurred in 7% of patients after PFO closure and in 12% of
      patients with underlying ASD. The annual incidence of new-onset AF was 2.5% and
      4.1% in patients with PFO and ASD, respectively. Generally, patients with new
      onset AF were older than those without AF. Device type or size did not influence
      the occurrence of AF. In the group of patients with PFO, residual shunt was more
      common in patients with AF compared with the non-AF group. In conclusion, AF is
      more common after PFO and ASD closure compared with the general population;
      although device type or size did not impact the occurrence of AF, residual shunt
      may influence the occurrence of AF after intervention in patients with underlying
      PFO.

PMID- 18805120
TI  - Comparative outcome of bidirectional Glenn shunt in patients with pulmonary
      vascular resistance > or = 3.5 woods units versus < 3.5 woods units.
AB  - Moderate to severe pulmonary hypertension is considered to be an absolute
      contraindication to the performance of bidirectional Glenn (BDG) shunting.
      However, BDG shunting has been performed in young children with pulmonary
      hypertension associated with unrestricted pulmonary blood flow. In this study,
      the medical records of patients who underwent BDG starting from October 2000 to
      March 2004 were reviewed. Patients were divided into 2 groups on the basis of
      indexed pulmonary vascular resistance (PVRI) measured in room air: a high-risk
      group (n = 12) with PVRI > or = 3.5 Woods units (WU)/m(2) and a low-risk group (n
      = 28) with PVRI <3.5 WU/m(2) in room air. The 2 groups were comparable with
      respect to age, weight, ventricular morphology, pulmonary arterial anatomy, and
      atrioventricular valve function. Mean pulmonary arterial pressure and PVRI were
      significantly higher in the high-risk group compared with the low-risk group
      (39.2 +/- 20.7 vs 15.1 +/- 6.25 mm Hg, p <0.002, and 6.0 +/- 2.5 vs 1.6 +/- 0.82
      WU/m(2), p <0.0005, respectively). The ratio of pulmonary flow to systemic flow
      was 1.45 +/- 0.76 in the high-risk group and 1.24 +/- 1.2 in the low-risk group.
      In the high-risk group, mean PVRI decreased to 2.0 +/- 1.0 WU/m(2) on 100% oxygen
      (p <0.0005). A contraindication to Glenn shunting was PVRI >3.5 WU/m(2) on 100%
      oxygen. Hospital mortality was 17% (2 of 12) in the high-risk group and 4% (1 of
      28) in the low-risk group. Of 10 survivors in the high-risk group, 1 had
      undergone a Kawashima procedure, 7 had undergone Fontan procedures (with 1
      death), and 2 were awaiting the completion of Fontan procedures as of this
      writing. In conclusion, these preliminary data suggest that in young children
      with increased pulmonary flow, BDG shunting can be safely performed, despite the
      apparent elevation of pulmonary arterial pressure to inoperable levels, provided
      PVRI decreases to < or = 3.5 WU/m(2) on 100% oxygen.

PMID- 18805121
TI  - Long-term risk of fatal malignancy following pediatric radiofrequency ablation.
AB  - Children undergoing radiofrequency ablation (RFA) are believed to be at increased
      risk of developing malignancy caused by radiation, although the magnitude of this
      risk is incompletely understood. We previously reported a strategy to reduce
      radiation exposure during pediatric RFA. In a cohort of 15 subjects (median age
      12 years, range 9 to 17), radiation was measured using dosimeters at 5 sites. The
      risk of malignancy using measured radiation absorbed dose was calculated.
      International Council for Radiation Protection 60 risk estimates were applied to
      calculate absorbed organ doses. Median duration of combined biplane fluoroscopy
      was 14.4 minutes. Of the 5 dosimeter locations, the right scapular location had
      the highest median radiation exposure (43 mGy). Incorporating data from the 5
      dosimeters, the risk model calculated that the organ with the greatest absorbed
      dose and at greatest risk of malignancy was the lung, followed by bone marrow,
      then breast. Thyroid and ovary exposures were negligible. The increased lifetime
      risk of fatal malignancy was 0.02% per single RFA procedure. In conclusion, with
      appropriate measures to reduce radiation exposure, the increased risk of
      malignancy after a single RFA procedure in children is low. These data should be
      of help counseling families and will contribute to analysis of the relative risk
      reduction benefits of such novel imaging approaches as a magnetic resonance
      imaging-based catheterization laboratory.

PMID- 18805122
TI  - Frequency of migraine headache relief following patent foramen ovale "closure"
      despite residual right-to-left shunt.
AB  - Retrospective studies have shown improvement in migraines after patent foramen
      ovale (PFO) closure. To date, no study has evaluated whether the completeness of
      closure affects headache status; therefore, the objective of this study was to
      evaluate the impact of residual right-to-left shunt (RLS) on migraine symptoms
      after transcatheter PFO closure in migraineurs with and without aura. This was a
      small-series, single-center, retrospective analysis of late follow-up data on 77
      patients with presumed paradoxical embolism and migraine who underwent PFO
      closure for secondary stroke prevention. Power M-mode transcranial Doppler was
      used to assess RLS at baseline and 6 and 12 months after closure. A standardized
      migraine questionnaire was administered at baseline and 6, 12, and 24 months
      after closure. Fifty-five (71%) patients had migraine with aura. Final closure
      and migraine status were available for 67 patients; 23 (34%) had incomplete PFO
      closure, defined as 30 embolic tracks detected at final power M-mode transcranial
      Doppler examination (median 366 days, 95% confidence interval 332 to 474).
      Migraine relief (> or = 50% reduction in frequency) was independent of closure
      status (77% complete closure vs 83% incomplete closure, p = 0.76) at late follow
      up (540 days, 95% confidence interval 537 to 711). Migraineurs with aura were 4.5
      times more likely to experience migraine relief than migraineurs without aura. In
      conclusion, migraine relief may occur despite residual RLS after transcatheter
      PFO closure, which may suggest a reduction in RLS burden below a neuronal
      threshold that triggers migraine; however, this warrants further investigation.
      Migraine with aura may be an independent predictor of relief after PFO closure.

PMID- 18805123
TI  - Usefulness of hypertensive blood pressure response during a single-stage exercise
      test to predict long-term outcome in patients with peripheral arterial disease.
AB  - The prognostic value of a hypertensive blood pressure (BP) response is still
      unclear. Therefore, the prognostic value of a hypertensive BP response in
      patients during single-stage exercise testing for peripheral arterial disease
      (PAD) on long-term mortality and major adverse cerebrovascular and cardiac events
      (MACCEs) was investigated. In addition, effects of statin, beta-blocker, and
      aspirin use in patients with known or suspected PAD were studied. A total of
      2,109 patients were enrolled in an observational prospective study from 1993 to
      2005. Hypertensive BP response was defined as an increase in systolic BP > or =
      55 mm Hg (95(th) percentile within our population) after a single-stage treadmill
      exercise test. The outcome was obtained by using the civil registries, and a
      questionnaire about cardiac events was sent to all survivals. Hypertensive BP
      response was associated with increased risk of long-term mortality (hazard ratio
      [HR] 1.42, 95% confidence interval [CI] 1.12 to 1.80) and MACCEs (HR 1.47, 95% CI
      1.09 to 1.97). After adjustments for clinical risk factors and propensity score,
      baseline statin use was associated with reduced risk of long-term mortality (HR
      0.59, 95% CI 0.44 to 0.79), and statin, beta-blocker, and aspirin use were
      associated with reduced risk of MACCEs (HR 0.59, 95% CI 0.43 to 0.81; HR 0.75,
      95% CI 0.60 to 0.95; HR 0.73, 95% CI, 0.57 to 0.92, respectively). In conclusion,
      hypertensive BP response at exercise in patients with known or suspected PAD is
      an important independent risk factor for all-cause long-term mortality and
      MACCEs, whereas statin, beta-blocker, and aspirin use were associated with an
      improved outcome.

PMID- 18805124
TI  - Incidence of vena cava thrombosis in the United States.
AB  - From 1979 through 2005, vena cava thrombosis (either superior or inferior) was
      diagnosed in 99,000 hospitalized patients. Most, 78%, had isolated vena cava
      thrombosis. From 2000 to 2005, 5,000 patients were diagnosed yearly with vena
      cava thrombosis (1.5% of patients hospitalized with deep venous thrombosis). The
      population-based incidence of diagnosis of vena cava thrombosis from 2001 to 2005
      was 1.7 in 100,000. The incidence increased with age. It was rare in Asian
      Americans. Pulmonary embolism occurred in 12% of patients with isolated vena cava
      thrombosis. Cancer was frequently associated with vena cava thrombosis (37.5%).
      Among all patients hospitalized with cancer, however, it was an uncommon
      complication (0.07%). In conclusion, isolated vena cava thrombosis is an uncommon
      cause of pulmonary embolism but may be considered if the veins of the extremities
      show no deep venous thrombosis.

PMID- 18805125
TI  - Cardiovascular risk after bariatric surgery for obesity.
AB  - Obese patients have an increased prevalence of cardiovascular (CV) risk factors,
      which improve with bariatric surgery, but whether bariatric surgery reduces long
      term CV events remains ill defined. A systematic review of published research was
      conducted, and CV risk models were applied in a validation cohort previously
      published. A standardized MEDLINE search using terms associated with obesity,
      bariatric surgery, and CV risk factors identified 6 test studies. The validation
      cohort consisted of a population-based, historical cohort of 197 patients who
      underwent Roux-en-Y gastric bypass and 163 control patients, identified through
      the Rochester Epidemiology Project. Framingham and Prospective Cardiovascular
      Munster Heart Study (PROCAM) risk scores were applied to calculate 10-year CV
      risk. In the validation cohort, absolute 10-year Framingham risk score for CV
      events was lower at follow-up in the bariatric surgery group (7.0% to 3.5%, p
      <0.001) compared with controls (7.1% to 6.5%, p = 0.13), with an intergroup
      absolute difference in risk reduction of 3% (p <0.001). PROCAM risk in the
      bariatric surgery group decreased from 4.1% to 2.0% (p <0.001), whereas the
      control group exhibited only a modest decrease (4.4% to 3.8%, p = 0.08). Using
      mean data from the validation study, the trend and directionality in risk was
      similar in the Roux-en-Y group. The test studies confirmed the directionality of
      CV risk, with estimated relative risk reductions for bariatric surgery patients
      ranging from 18% to 79% using the Framingham risk score compared with 8% to 62%
      using the PROCAM risk score. In conclusion, bariatric surgery predicts long-term
      decreases in CV risk in obese patients.

PMID- 18805126
TI  - Usefulness of N-terminal pro-brain natriuretic peptide as a biomarker of the
      presence of carcinoid heart disease.
AB  - We sought to investigate whether N-terminal pro-brain natriuretic peptide (NT-pro
      BNP) can be used as a biomarker for the detection of carcinoid heart disease
      (CHD); 200 patients with carcinoid syndrome were screened for CHD using
      transthoracic echocardiography. A carcinoid score was formulated to quantify
      severity of CHD. NT-pro-BNP was measured in all patients before echocardiography.
      Patients were categorised into New York Heart Association class. CHD was present
      in 39 patients (19.5%). NT-pro-BNP was significantly higher in those with CHD
      (median 1,149 pg/ml) than in those without CHD (median 101 pg/ml, p <0.001). The
      sensitivity and specificity of NT-pro-BNP at a cut-off level of 260 pg/ml for
      detection of CHD were 0.92 and 0.91, respectively. NT-pro-BNP positively
      correlated both with carcinoid score (r = 0.81, p <0.001) and New York Heart
      Association class (p <0.001). The number of patients screened to diagnose 1 case
      of CHD decreased from 5.1 to 1.4. In conclusion, NT-pro-BNP seems to be an
      excellent biomarker of CHD. A high negative predictive value may allow it to
      provide a screening test for CHD.

PMID- 18805127
TI  - Defining optimal research study design for cardiovascular imaging using computed
      tomography angiography as a model.
AB  - Patients, physicians, and payers are facing a significant increase in
      cardiovascular (CV) imaging use, resulting in skyrocketing societal costs,
      without clear improvement in patient outcomes. The need for studies evaluating
      the effects of CV imaging that assess appropriate end points is critical to
      address continued concerns over the lack of well-designed clinical studies. Thus,
      the investigators propose a framework, using computed tomographic angiography as
      a model, that should be considered in the optimal design of future imaging
      research and would potentially provide payers with data to make appropriate
      reimbursement decisions. The inclusion of risk stratification, randomization,
      multiple-site participation, and multigeography site enrollment are key elements
      in the construction of such studies. Meaningful end points with regard to
      operating characteristics, downstream testing, CV event rates, outcomes, and
      costs are essential to appropriately evaluate any new imaging technology. Only
      once better level evidence is formed to support CV imaging can the central issues
      of quality and appropriateness of CV imaging truly be evaluated. If the CV
      community does not embrace this type of scientific evaluation of CV imaging
      modalities and fails to adequately identify the value in these techniques, it may
      ultimately lose the ability to use them to provide optimal care to its patients.

PMID- 18805128
TI  - Unconventional electrocardiographic signs of ischemia during exercise testing.
AB  - Because of the failure to consider some of the unconventional
      electrocardiographic signs of ischemia during exercise testing, its sensitivity
      and specificity are lower than optimum. Two cases are presented to illustrate how
      precordial peaking of the T waves and lead-strength calculations in patients with
      low-voltage R waves can be used to improve the diagnostic power of exercise
      testing. Other rarely used electrocardiographic changes during exercise testing
      include ST elevation in lead aVR, an increase in P-wave duration, and ST
      depression in premature ventricular complexes. In conclusion, this experience
      demonstrates that the routine consideration of these electrocardiographic changes
      will result in significant increases in the sensitivity and specificity of
      exercise testing.

PMID- 18805129
TI  - Pregnancy associated plasma protein a as a quick and sensitive biomarker in early
      phase of acute coronary syndrome.

PMID- 18805130
TI  - Suboptimal percutaneous coronary intervention.

PMID- 18805131
TI  - Prognostic value of lesion classification for the clinical outcome after stent
      placement.

PMID- 18805132
TI  - Mission critical: thoracic surgery education reform.

PMID- 18805133
TI  - You never know unless you try.

PMID- 18805134
TI  - Results of primary surgery with T4 non-small cell lung cancer during a 25-year
      period in a single center: the benefit is worth the risk.
AB  - BACKGROUND: The purpose of this study was to assess operative mortality,
      morbidity, and long-term results of patients with surgically resected T4 non
      small cell lung carcinoma. METHODS: A retrospective review of 271 patients with
      T4 non-small cell lung carcinoma between 1981 and 2006 was undertaken. They were
      divided into four subgroups: 126 patients with superior sulcus tumors, 92 with
      carinal involvement, 39 with superior vena cava replacement, and 14 with the
      tumor invading other mediastinal structures. There were 221 men and 50 women with
      a mean age of 56.3 years. Resection was complete in 249 (92%) patients. The
      pathologic N status was N0/N1 in 208 and N2/N3/M1 in 63 patients. RESULTS:
      Operative mortality and morbidity rates were 4% and 35%, respectively. Overall 5
      year survival rate was 38.4%. It was 36.6% for superior sulcus tumor, 42.5% for
      carinal involvement, 29.4% for superior vena cava replacement, and 61.2% for
      mediastinal group. By multivariate analysis, only three factors influenced
      survival: nodal status (N0/N1 versus N2/3/M1; 43% versus 17.7% at 5 years,
      respectively; p = 0.01), complete resection (R0 versus R1; 40.4% versus 15,9%,
      respectively; p = 0.006), and invasion of the subclavian artery (with versus
      without invasion; 24.9% versus 41.7%, respectively, p = 0.02). CONCLUSIONS: In
      highly qualified centers, radical surgery of T4 N0/N1 non-small cell lung
      carcinoma can be performed with a 4% mortality rate and may yield a 43% 5-year
      survival rate. These results seem to indicate primary surgery as the treatment of
      choice for T4 non-small cell lung carcinoma, whenever a complete resection is
      thought to be technically feasible and the patient's condition is compatible with
      the extent of the planned surgery.

PMID- 18805135
TI  - Subcategorization of resectable non-small cell lung cancer involving neighboring
      structures.
AB  - BACKGROUND: Although the prognoses of patients with resectable lung cancer
      involving neighboring structures vary, the current tumor-nodes-metastasis (TNM)
      classification system does not elucidate criteria for tumor subcategorization.
      METHODS: We studied 196 consecutive patients who underwent resection of non-small
      cell lung cancer involving neighboring structures at the Aichi Cancer Center
      Hospital and were diagnosed as pathologic T3 diseases using the current staging
      system. Tumors were divided into six groups based on the involved neighboring
      structures: parietal or mediastinal pleura, subpleural soft tissue, ribs, main
      bronchus, pericardium, and diaphragm. RESULTS: The overall 5-year survival rate
      was 39.8%. The survival rates for the six groups were: pleura (n = 62), 54.8%;
      subpleural soft tissue (n = 50), 30.0%; rib (n = 25), 24.0%; main bronchus (n =
      33), 48.5%; pericardium (n = 14), 21.4%; and diaphragm (n = 12), 33.3%. The
      combined pleura and bronchus groups (n = 95) demonstrated significantly better
      survival outcome than the other groups (n = 101): 52.6% and 27.7%, respectively
      (p = 0.0002). Furthermore, among 108 patients with pT3N0 (stage IIB) disease, the
      prognostic difference between the pleura and bronchus groups (n = 50) and the
      other groups (n = 58) was significant: 64.0% and 25.9%, respectively (p <
      0.0001). Similar results were confirmed in patients with complete resection (n =
      159). CONCLUSIONS: Subcategorization of resectable lung cancer involving
      neighboring structures resulted in tumor groups infiltrating pleura or main
      bronchus, and those involving subpleural structures, pericardium, or diaphragm.

PMID- 18805136
TI  - Subcategorization of lung cancer based on tumor size and degree of visceral
      pleural invasion.
AB  - BACKGROUND: Lung cancer staging system proposed in 2007 adopts detailed tumor
      size cut-off values. Alternatively, visceral pleural invasion is deemed an
      important prognosticator, but has not been easily incorporated into the staging
      system. METHODS: We studied 1,245 patients with resected nonsmall-cell lung
      cancer. Among patients with current pathologic stage IB (pT2N0M0) disease, those
      with worse prognosis were reclassified as stage IIA based on tumor size and
      degree of visceral pleural invasion defined by the Japan Lung Cancer Society: P0
      = no pleural involvement beyond elastic layer; P1 = infiltration beyond elastic
      layer without exposure to pleural surface; and P2 = exposure to pleural surface.
      RESULTS: The current pT2 category was divided into five groups based on size
      (<or= 3, > 3 to <or= 5, and > 5 cm) and degree of visceral pleural invasion (P0-1
      or P2). Five-year survival rates in patients with P0-1 tumors greater than 3 cm
      to 5 cm or less were significantly better (59.5%) than those with tumors greater
      than 5 cm or P2 tumors (37.5% to 47.3%; p = 0.0014); we defined these two groups
      as T2a and T2b, respectively, and classified T2aN0M0 as stage IB and T2bN0M0 as
      stage IIA together with the current T1N1M0. Five-year survival rates for the
      modified IB and IIA diseases were 70.6% and 60.4%, respectively (p = 0.0414).
      CONCLUSIONS: Modified subcategorization of the pT2 category resulted in T2a (> 3
      to <or= 5 cm and P0-1) and T2b (> 5 cm or P2). Detailed assessment of the degree
      of visceral pleural invasion could provide more information on tumor
      characteristics and complement the pathologic staging of lung cancer.

PMID- 18805137
TI  - Invited commentary.

PMID- 18805138
TI  - The impact of multiple metastatic nodal stations on survival in patients with
      resectable N1 and N2 nonsmall-cell lung cancer.
AB  - BACKGROUND: The aim of the study was to identify common prognostic factors in
      nonsmall-cell lung cancer (NSCLC) with N1 and N2 nodal involvement. METHODS: A
      retrospective review of NSCLC patients who underwent primary surgical resection
      without neoadjuvant chemotherapy was performed. In all, 280 patients were
      included in this study, and there were 132 patients with N1 disease (N1 group)
      and 148 patients with N2 disease (N2 group). The median follow-up period was 26
      months, and complete follow-up was possible in 269 patients (96%). RESULTS:
      Lobectomy was performed in 194 patients (69%), bilobectomy was performed in 43
      (15%), and pneumonectomy was performed in 43 (15%). Complete resection was
      possible in 273 patients (98%), and operative death occurred in 5 patients (2%).
      The overall and disease-free 5-year survival rates were 63% and 55%,
      respectively, in the N1 group, and 44% and 32%, respectively, in the N2 group (p
      < 0.05). The prognostic factors for overall survival in both the N1 and N2 groups
      were age and the number of metastatic nodal stations; however, N2 metastasis was
      not a significant prognostic factor in the multivariate analysis. The poor
      prognosis of the patients in the N2 group was due to the greater incidence of
      multiple node involvement in comparison with the N1 group (73% versus 15%; p <
      0.05). CONCLUSIONS: Multiple metastatic nodal stations was the common prognostic
      factor in resectable NSCLC patients with nodal metastasis, and mediastinal nodal
      involvement was associated with a higher chance of multiple-station metastasis in
      this study.

PMID- 18805139
TI  - Needlescopic lung biopsy for interstitial lung disease and indeterminate
      pulmonary nodules: a report on 65 cases.
AB  - BACKGROUND: We evaluated the feasibility and accuracy of a needlescopic procedure
      for lung biopsies in patients with interstitial lung disease or indeterminate
      pulmonary nodules. METHODS: Sixty-five patients (36 women; mean age, 51.3 +/-
      15.6; range, 13 to 76 years) underwent a needlescopic procedure to obtain lung
      biopsy specimens. Forty had indeterminate pulmonary nodules, and 25 had
      interstitial lung disease. A 2-mm needlescope and a 2-mm MiniSite Endo Grasp
      (Covidien, Norwalk, CT) were inserted at the sixth intercostal space along the
      middle and the posterior axillary line, respectively. Biopsy specimens were
      obtained using endostaplers. RESULTS: The average number of biopsy specimens was
      1.7 +/- 0.6 (range, 1 to 4). For 9 patients, a frozen specimen was sent twice to
      pathology. Complete resection was continued after intraoperative pathology
      confirmation in 13 patients (lobectomy, 7; segmentectomy, 3; mass removal, 1;
      metastasectomy, 2). The volume of lung tissue was 8.7 +/- 11.8 cm3 (range, 0.15
      to 55.44 cm3). The operation time was 58.7 +/- 37.5 minutes (range, 15 to 160
      minutes). The final pathologic results were confirmed in all patients. No
      thoracoscopic procedure was converted to an open thoracotomy. Three patients
      (4.3%) had prolonged air leakage (> 5 days), and the chest tube remained in the
      pleural space for 2.3 +/- 2.4 days (range, 1 to 8 days). CONCLUSIONS:
      Needlescopic operation for lung biopsies in patients with interstitial lung
      disease and indeterminate pulmonary nodules is a minimally invasive procedure
      that is safe and effective for obtaining a diagnosis in selected patients.

PMID- 18805140
TI  - Invited commentary.

PMID- 18805141
TI  - Endobronchial ultrasound-guided fine-needle aspiration of mediastinal lymph
      nodes: a single institution's early learning curve.
AB  - BACKGROUND: The gold standard for mediastinal lymph node evaluation is
      mediastinoscopy, which is invasive and allows access to only a limited number of
      mediastinal lymph node (MLN) stations (1, 2, 3, 4, and 7). Endobronchial
      ultrasound-guided fine-needle aspiration (EBUS-FNA) is emerging as a useful, less
      invasive technique that offers access to a wider range of MLN stations (2, 3, 4,
      7, 10, and 11). We report our initial experience with this procedure. METHODS:
      Using our prospectively maintained database, we performed a single-institution
      retrospective chart review. Our study group consisted of all patients at the
      University of Minnesota who underwent EBUS-FNA for evaluation of mediastinal
      lymphadenopathy or for thoracic malignancy staging from September 1, 2006,
      through December 15, 2007. To assess our learning curve, we plotted the
      cumulative sensitivity (%) and accuracy (%) of our EBUS-FNA results as a function
      of the number of procedures we performed. RESULTS: During the study period, 100
      patients underwent EBUS, 92 with FNA. Of these, 56 patients (34 women, 22 men;
      mean age, 60.4 +/- 13.7 years) met our inclusion criteria. We found no
      complications. After our first 10 procedures, the sensitivity of our EBUS-FNA
      results was 96.2%; accuracy was 97.8% (rates comparable with other large series
      in the literature). CONCLUSIONS: We conclude that the learning curve for EBUS-FNA
      for thoracic surgeons is about 10 procedures.

PMID- 18805142
TI  - Evaluation of isolated rib lesions with radionuclide-guided biopsy.
AB  - BACKGROUND: Isolated rib lesions detected on bone scanning can pose a diagnostic
      challenge, particularly in patients with a known primary cancer. The purpose of
      our study was to assess the diagnostic value of radionuclide-guided rib biopsy
      with an intraoperative gamma probe. METHODS: We conducted a retrospective chart
      review of 10 patients who underwent an intraoperative gamma probe-guided rib
      biopsy. Rib defects were identified by radionuclide bone scan. Patients received
      an intravenous dose of technetium 99m methylene diphosphonate within 6 hours
      before surgery. The approximate location of the rib defect was scanned with a
      hand-held gamma probe intraoperatively; an excisional rib biopsy was performed in
      the area with the highest tracer activity. RESULTS: Median age was 54 years
      (range, 40 to 83) and median body mass index was 32.5 (range, 23 to 52). Seven
      patients had a known primary extraosseous cancer and 3 patients had no history of
      cancer. Seven patients had pain at the time of initial evaluation. The median
      operative time was 45 minutes, median operative blood loss was 25 mL, and median
      length of stay was 1 day. Complications occurred in 2 patients: a pneumothorax
      that did not require treatment and a delayed hemothorax that required tube
      thoracostomy. Rib biopsy was accurate in all 10 patients; metastatic disease was
      found in 5 of 7 cancer patients. Pain improved or resolved in 4 patients.
      CONCLUSIONS: The evaluation of isolated rib lesions using radionuclide-guided rib
      biopsy with an intraoperative hand-held gamma probe is accurate and potentially
      therapeutic. Thoracic surgeons and oncologists should be aware of this approach.

PMID- 18805143
TI  - Invited commentary.

PMID- 18805144
TI  - Long-term outcome of lung and heart-lung transplantation for idiopathic pulmonary
      arterial hypertension.
AB  - BACKGROUND: The survival after lung and heart-lung transplantation for idiopathic
      pulmonary arterial hypertension has been reportedly the lowest among the major
      diagnostic categories of lung transplant recipients. METHODS: Retrospective
      analysis was performed for lung and heart-lung transplant recipients for
      idiopathic pulmonary arterial hypertension from 1982 to 2006. The patients were
      divided into 2 groups, based on the era; group 1: 1982 to 1993, and group 2: 1994
      to 2006. Since 1994, we have introduced our current protocols including
      prostaglandin E1 and nitroglycerin for donor lung preservation, and lung
      protection with cold and terminal warm blood pneumoplegia as well as
      immunosuppression with alemtuzumab induction. These modifications were introduced
      in different years over a wide span of time (1994 to 2003). RESULTS: Group 1 had
      59 patients (35 +/- 1 years old, ranging 15 to 53, 20 male and 39 female) with 7
      single lung, 11 double lung, and 41 heart-lung, whereas group 2 had 30 (43 +/- 2
      years old, ranging 17 to 65, 9 male and 21 female) with 2 single, 20 double, and
      8 heart-lung transplantations. The recipient age was significantly (p = 0.004)
      higher in group 2, and group 2 had significantly older (35 +/- 3 vs 26 +/- 1, p =
      0.002) and more female donors (73% vs 41%, p = 0.007) compared with group 1. The
      actuarial survival was significantly (p = 0.004) better in group 2 with 86% at 1
      year, 75% at 5 years, and 66% at 10 years compared with group 1 with 58% at 1
      year, 39% at 5 years, and 27% at 10 years. CONCLUSIONS: With our current
      pulmonary protection and immunosuppression, the long-term outcome of lung and
      heart-lung transplantation for idiopathic pulmonary arterial hypertension is
      excellent.

PMID- 18805145
TI  - Late retrograde perfusion of donor lungs does not decrease the severity of
      primary graft dysfunction.
AB  - BACKGROUND: The ideal preservation strategy has yet to be established in lung
      transplantation. This clinical study compares primary graft dysfunction using
      antegrade and retrograde perfusion of donor lungs. METHODS: Over a 6-year period,
      153 consecutive patients underwent lung transplantation in our institution. Group
      I consists of 65 patients who received lungs preserved with an antegrade flush of
      modified Euro-Collins solution. Group II includes 65 patients who received lungs
      preserved with an antegrade flush of low-potassium dextran (LPD) solution. Group
      III consists of 23 patients who received lungs preserved with an antegrade and a
      preimplantation retrograde flush of LPD solution. Endpoints evaluated were the
      following: acute lung injury (ALI) score, time to achieve a fraction of inspired
      oxygen (Fio2) of 40% and a positive end-expiratory pressure (PEEP) of 5, length
      of ventilation, length of intensive care unit (ICU) stay, 90-day operative
      mortality, and patient survival rates. RESULTS: The patient demographic data,
      underlying diagnosis, number of single and double lung transplants, use of
      cardiopulmonary bypass, and mean ischemic times were similar in all 3 groups. The
      mean ALI score (6.2, 5.8, and 6.0) and the median length of ventilation (23.5,
      24.0, and 27.0 hours) in groups I, II, and III, respectively, were not
      significantly different. The length of ICU stay, the 90-day operative mortality,
      and the survival rates were not significantly different in the 3 groups.
      CONCLUSIONS: Our results suggest that late retrograde perfusion of donor lungs
      does not decrease the severity of primary graft dysfunction when compared with
      standard antegrade techniques.

PMID- 18805146
TI  - Invited commentary.

PMID- 18805147
TI  - Assessment of treatment response and recurrence in esophageal carcinoma based on
      tumor length and standardized uptake value on positron emission tomography
      computed tomography.
AB  - BACKGROUND: Previous studies demonstrated that a decrease of the standardized
      uptake value between pretreatment and posttreatment positron emission tomography
      (PET) scans can predict histopathologic treatment response in patients with
      esophageal cancer. METHODS: Forty-seven patients who underwent PET-computed
      tomography (CT) scans before (scan 1) and after (scan 2) neoadjuvant
      chemoradiotherapy and during the follow-up period after surgery (scan 3) were
      included in this study. It was evaluated whether decrease of metabolic tumor
      length between scan 1 and scan 2 can predict histopathologic response to
      treatment. Moreover, the value of PET-CT was compared with PET in the assessment
      of tumor recurrence based on a visual analysis of scan 3. Reference standards for
      treatment response and recurrence were histopathology results. RESULTS: The
      reduction of tumor length between before and after chemoradiotherapy scans
      (between scan 1 and scan 2) was a better predictor of histopathologic response
      and of time to recurrence than the decrease in standardized uptake value. The
      most accurate differentiation was achieved when using a cut-off value of 33%
      reduction of the initial tumor length. Using this threshold to define metabolic
      response, the sensitivity was 91% (19 of 21) and the specificity was 92% (24 of
      26) for predicting histopathologic treatment response. Based on a visual
      analysis, PET-CT was more accurate than PET in the differentiation of tumor
      recurrence from posttreatment tissue changes. Integrated PET-CT achieved a
      sensitivity of 91% (48 of 53) and a specificity of 81% (30 of 37) in identifying
      sites of tumor recurrence, compared with 83% (44 of 53) and 65% (24 of 37) with
      PET. CONCLUSIONS: Decrease of tumor length was shown to be a better predictor of
      treatment response and disease-free survival than decrease of standardized uptake
      value. Furthermore, PET-CT is more accurate in the evaluation of recurrence than
      PET.

PMID- 18805148
TI  - Invited commentary.

PMID- 18805149
TI  - Off-pump coronary bypass provides reduced mortality and morbidity and equivalent
      10-year survival.
AB  - BACKGROUND: This study compared in-hospital major adverse cardiac events (MACE)
      and long-term survival after off-pump (OPCAB) vs on-pump (CPB) coronary artery
      bypass grafting (CABG). METHODS: Reviewed were 12,812 consecutive isolated CABG
      patients from 1997 to 2006. A propensity score (PS), including 40 preoperative
      risk factors, balanced characteristics between OPCAB and CPB groups. Multiple
      logistic regression models tested whether gender or surgery type, or their
      interaction, were associated with in-hospital mortality and MACE. A proportional
      hazards regression model and Kaplan-Meier curves related long-term survival with
      gender, surgery type, and their interaction, adjusted for PS and age. RESULTS:
      OPCAB was associated with a significant reduction in operative mortality
      (adjusted odds ratio [AOR], 0.68; p = 0.045), stroke (AOR, 0.48; p < 0.001), and
      MACE (AOR, 0.66; p = 0.018). Female gender was associated with higher rates of
      death (AOR, 1.93), stroke (AOR, 1.82), myocardial infarction (AOR, 2.19), and
      MACE (AOR, 1.97; each p < 0.001). Women disproportionately benefited from OPCAB
      in operative mortality (p = 0.04). Odds of death for women on CPB were higher
      than for women treated with OPCAB (AOR, 2.07, p = 0.005). Odds of death for men
      on CPB were not significantly higher than for men treated with OPCAB (AOR, 1.16,
      p = 0.51). Male gender was associated with longer-term survival (p = .011), but
      surgery type (OPCAB vs CPB) was not (p = 0.23). CONCLUSIONS: OPCAB provides
      significant early mortality and morbidity advantages, especially for women.
      During the 10-year follow-up, OPCAB and CPB result in similar survival,
      regardless of gender.

PMID- 18805150
TI  - Immediate and intermediate outcome after off-pump and on-pump coronary artery
      bypass surgery in patients with unstable angina pectoris.
AB  - BACKGROUND: We have evaluated the immediate and intermediate outcome after off
      pump (OPCAB) and conventional on-pump coronary artery bypass surgery (CCAB) in
      patients with unstable angina pectoris requiring nitrates infusion until arrival
      in the operating room. METHODS: A consecutive series of 153 and 161 patients with
      unrelenting angina pectoris underwent CCAB and OPCAB, respectively. Conversion
      from OPCAB to beating heart surgery with perfusion occurred in 4 patients.
      RESULTS: The OPCAB patients had a significantly higher operative risk than CCAB
      patients (logistic European System for Cardiac Operative Risk Evaluation
      [EuroSCORE]: 13.8 +/- 12.8% vs 10.5 +/- 10.0%, p = 0.005). In the overall series,
      a lower 30-day postoperative mortality was observed among OPCAB patients (1.9% vs
      3.9%, p = 0.33), the difference increased along the logistic EuroSCORE tertiles
      (upper tertile: 3.2% vs 9.5%, p = 0.14), but failed to reach statistical
      significance. Similar results have been observed among one-to-one propensity
      score matched pairs. The results of three surgeons who treated most of their
      patients (96.9%) with OPCAB were compared with those of three surgeons who used,
      in most of cases (97.1%), the CCAB technique. When adjusted for logistic
      EuroSCORE, patients operated on by CCAB surgeons had a significantly higher 30
      day postoperative mortality (7.1% vs 2.1%, p = 0.04; odds ratio [OR] 10.143; 95%
      confidence interval [CI] 1.084 to 94.945) as well as a higher risk of combined
      adverse events (47.1% vs. 35.1%, p = 0.009; OR 2.586; 95% CI 1.274 to 5.250).
      CONCLUSIONS: This study provided further evidence on the safety and efficacy of
      OPCAB in the treatment of high-risk patients. A dedicated approach to OPCAB seems
      to provide particularly good results. Such findings further support a more
      confident approach with OPCAB in these patients.

PMID- 18805151
TI  - Utilization and outcomes of unprotected left main coronary artery stenting and
      coronary artery bypass graft surgery.
AB  - BACKGROUND: Limited contemporary information is available on outcomes for
      patients with unprotected left main coronary artery (LMCA) disease who are
      revascularized. METHODS: We examined the relative frequency, severity of illness,
      and outcomes of stenting and coronary artery bypass graft (CABG) surgery for
      treating unprotected LMCA disease in New York between January 1, 2000 and
      December 31, 2004. A total of 16,336 (98.7%) patients who underwent CABG surgery
      and 212 (1.3%) who underwent stenting were included in this study. RESULTS: Stent
      patients had higher preprocedural severity of illness (eg, they were older, more
      likely to be female, and had more comorbidities). A total of 135 stent patients
      were matched to 135 CABG patients on baseline characteristics identified by a
      propensity model as predictors of type of procedure received. At the end of
      follow-up on December 31, 2004, the respective 2-year survival rates were 94.1%
      and 82.0% (hazard ratio = 0.32, p = 0.005) for the 135 pairs of matched CABG and
      stent patients. The respective 2-year rates for freedom from subsequent
      revascularization were 93.7% and 62.7% (hazard ratio = 0.15, p < 0.001). In the
      drug-eluting stent era between October 1, 2003 and December 31, 2004, the same
      trends in mortality (hazard ratio = 0.73, p = 0.69) and repeat revascularization
      (hazard ratio = 0.10, p = 0.03) were observed among the 56 pairs of matched CABG
      and drug-eluting stent patients. CONCLUSIONS: Most patients with LMCA disease who
      needed coronary revascularization received CABG surgery; stent patients were
      sicker. This study found that surgery patients experienced lower risk of long
      term death and repeat revascularization. However, more studies comparing these
      procedures are needed, especially in the drug-eluting stent era.

PMID- 18805152
TI  - Preoperative Angiotensin-converting enzyme inhibitors and acute kidney injury
      after coronary artery bypass grafting.
AB  - BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors confer renal
      protection in different clinical settings. No final conclusions are available on
      the renal benefits of ACE inhibitors after coronary artery bypass grafting
      (CABG). Because ACE inhibitors decrease glomerular perfusion pressure, they may
      exacerbate kidney injury during cardiopulmonary bypass (CPB)-related
      hypoperfusion. We evaluated the effect of preoperative ACE inhibitors on acute
      kidney injury (AKI) after CABG. METHODS: A propensity score-based analysis of 536
      patients undergoing CABG on CPB was performed, among which 281 received ACE
      inhibitors preoperatively. Patients with preoperative end-stage renal failure
      requiring dialysis were excluded. Postoperative AKI was defined as 50% or more
      decrease in the glomerular filtration rate from preoperative or postoperative
      mechanical renal support. RESULTS: After CABG, AKI developed in 49 patients
      (9.1%), and 23 (4.2%) required dialysis. The incidence of AKI was 6.4% in
      patients who received preoperative ACE inhibitors and 12.2% in patients who did
      not (p = 0.02). The incidence of AKI requiring dialysis was 2.4% in the treatment
      group and 6.3% in controls (p = 0.03). After adjusting for propensity score and
      covariates, preoperative ACE inhibitors were found to reduce the incidence of
      postoperative AKI (odds ratio, 0.48; 95% confidence interval, 0.23 to 0.77; p =
      0.04). Other independent predictors were age, preoperative glomerular filtration
      rate, left ventricular ejection fraction of less than 0.35, preoperative use of
      intraaortic balloon pump, emergency operation, and CPB time. CONCLUSIONS:
      Preoperative ACE inhibitors are associated with a reduced rate of AKI after on
      pump CABG surgery.

PMID- 18805153
TI  - Invited commentary.

PMID- 18805154
TI  - Effects of shed mediastinal blood on cardiovascular and pulmonary function: a
      randomized, double-blind study.
AB  - BACKGROUND: Shed mediastinal blood during cardiopulmonary bypass (cardiotomy
      blood) contains fat, particulate matter, and vasoactive mediators that can
      adversely affect the pulmonary and systemic vasculature, as well as impair gas
      exchange. Our aim was to evaluate the effects of processing cardiotomy blood on
      cardiovascular and pulmonary function after cardiac surgery. METHODS: Patients
      undergoing coronary artery bypass or aortic valve surgery, or both, using
      cardiopulmonary bypass were randomly allocated to receiving processed (treated, n
      = 132) or unprocessed shed blood (control, n = 134) In the treated group, shed
      blood was processed by centrifugation, washing, and additional filtration.
      Pulmonary function, arterial and venous blood gases, and hemodynamics were
      measured before, immediately after, and 2 hours after cardiopulmonary bypass in a
      consecutive subset of patients (n = 154). Patients and treating physicians were
      blinded to treatment assignment. RESULTS: Preoperative characteristics were
      similar between groups. There were no significant differences between groups in
      indexes of pulmonary mechanical function at any of the measured time points.
      Patients in the treated group demonstrated reduced pulmonary and systemic
      vascular resistance (both p < 0.01) as well as increased cardiac index in the
      perioperative period (2.6 +/- 0.07 versus 2.3 +/- 0.06 L . min(-1) . m(-2) at 2
      hours after CPB, p = 0.004). Larger volumes of cardiotomy blood were associated
      with greater changes in systemic and pulmonary vascular resistance. Indicators of
      pulmonary gas exchange were similar between groups at all measured time points.
      Treated patients demonstrated a trend toward reduced length of ventilation (11.0
      +/- 1.9 versus 13.9 +/- 2.4 hours, p = 0.12). CONCLUSIONS: Processing of shed
      mediastinal blood improves cardiopulmonary hemodynamics and may reduce
      ventilatory requirements after cardiac surgery.

PMID- 18805155
TI  - Invited commentary.

PMID- 18805156
TI  - The impact of peripheral vascular disease on long-term survival after coronary
      artery bypass graft surgery.
AB  - BACKGROUND: Although peripheral vascular disease is known to negatively affect
      overall survival, its effects on survival after surgical myocardial
      revascularization have not been well described. The objective of this study was
      to examine the impact of peripheral vascular disease on long-term survival after
      coronary artery bypass grafting. METHODS: We reviewed records of 1,164
      consecutive patients (370 with peripheral vascular disease and 794 without it)
      who underwent primary isolated coronary artery bypass graft surgery between 1997
      and 2007. Univariate and multivariate logistic regression methods were used to
      analyze variables associated with early outcomes. We assessed long-term survival
      by using Kaplan-Meier curves generated by log-rank tests, adjusting for
      confounding factors with Cox proportional hazards regression analysis. RESULTS:
      Patients with peripheral vascular disease were generally sicker and had more
      comorbidities than patients without peripheral vascular disease. The presence of
      peripheral vascular disease does not predict increased rates of 30-day mortality
      or major adverse cardiac events. However, after controlling for potential
      confounding factors, patients with peripheral vascular disease had a
      significantly worse 9-year survival rate than patients without peripheral
      vascular disease (72.9% +/- 4.1% versus 82.8% +/- 2.4%; adjusted hazard ratio,
      1.7; 95% confidence interval: 1.2 to 2.4; p = 0.004). CONCLUSIONS: Although
      peripheral vascular disease does not affect early outcomes in coronary artery
      bypass operations, it is an independent predictor of poor long-term survival
      among patients undergoing coronary artery bypass graft surgery. Identifying the
      mechanism that underlies this difference is important for improving survival in
      patients with peripheral vascular disease who undergo surgical myocardial
      revascularization.

PMID- 18805157
TI  - Influence of diabetes mellitus on long-term survival in systematic off-pump
      coronary artery bypass surgery.
AB  - BACKGROUND: Diabetic patients generally present a more diffuse and calcified
      coronary artery disease than nondiabetic patients that can affect long-term
      outcome especially if an off-pump coronary artery bybass graft (OPCABG) technique
      is used. The aim of this study was to compare long-term results of OPCABG surgery
      for diabetic and nondiabetic patients. METHODS: This is a retrospective analysis
      of prospectively gathered data over a 10-year period of 1,000 consecutive and
      systematic OPCABG patients operated on between September 1996 and April 2004.
      Average follow-up period was 66 +/- 28 months and was 97% complete. Overall
      survival as well as occurrence of major adverse cardiac events in diabetic and
      nondiabetic patients were specifically studied. RESULTS: In all, 278 diabetic
      patients and 722 nondiabetic patients were treated. There was no difference in 30
      day mortality between the two groups (p = 0.70). Diabetic patients had more
      postoperative acute renal insufficiency (p = 0.01) and infections (sepsis; p =
      0.002), and deep sternal infections (p = 0.04) Ten-year survival (p = 0.006) and
      survival free of major adverse cardiac events (p = 0.02) was decreased in the
      diabetic group. Age (hazard ratio [HR] = 1.06), peripheral vascular disease (HR =
      1.72), carotid disease (HR = 1.53), congestive heart failure (HR = 1.51),
      incomplete revascularization (HR = 2.37), chronic renal insufficiency (HR =
      1.93), left ventricular ejection fraction (HR = 0.13), and a lesser use of
      multiple internal thoracic artery grafts (HR = 0.67), but not diabetes mellitus
      (p = 0.13) were significant determinants of long-term mortality. Similarly,
      peripheral vascular disease (HR = 1.92), chronic renal insufficiency (HR = 2.36),
      emergent operation (HR = 1.71), chronic obstructive pulmonary disease (HR =
      1.76), previous percutaneous coronary intervention (HR = 1.66), left ventricular
      ejection fraction (HR = 0.26), ischemic mitral regurgitation (HR = 1.83), and a
      lesser use of multiple internal thoracic artery grafts (HR = 0.72) were
      determinants of decreased survival free of major adverse cardiac events but not
      diabetes (p = 0.2). Breaking down the major adverse cardiac events, diabetes was
      found an independent predictive factor of recurrent myocardial infarction (HR =
      1.85) and a borderline cause of readmission for congestive heart failure (p =
      0.06). Need for new revascularization was comparable for both population (p =
      0.37). CONCLUSIONS: In our series of OPCABG surgery patients, diabetic patients
      had a comparative operative mortality and perioperative myocardial infarction
      rate as nondiabetic patients. However, they had an increased prevalence of
      postoperative acute renal insufficiency and infections. They also had a worse
      outcome than nondiabetic patients, but that was mainly due to a higher prevalence
      of preoperative comorbidities and a lesser use of multiple internal thoracic
      artery grafts. However, diabetes itself was a potential risk factor for long-term
      occurrence of myocardial infarction and congestive heart failure.

PMID- 18805158
TI  - Uncoupling of myocardial beta-adrenergic receptor signaling during coronary
      artery bypass grafting: the role of GRK2.
AB  - BACKGROUND: Cardiopulmonary bypass (CPB) and cardioplegic arrest during cardiac
      surgery leads to desensitization of myocardial beta-adrenergic receptors (beta
      ARs). Impaired signaling through this pathway can have a detrimental effect on
      ventricular function and increased need for inotropic support. The mechanism of
      myocardial beta-AR desensitization during cardiac surgery has not been defined.
      This study investigates the role of G protein-coupled receptor kinase-2 (GRK2), a
      serine-threonine kinase which phosphorylates and desensitizes agonist-occupied
      beta-ARs, as a primary mechanism of beta-AR uncoupling during coronary artery
      bypass grafting (CABG) with CPB and cardioplegic arrest. METHODS: Forty-eight
      patients undergoing elective CABG were enrolled in this study. Myocardial beta-AR
      signaling was assessed by measuring total beta-AR density and adenylyl cyclase
      activity in right atrial biopsies obtained before CPB and just before weaning
      from CPB. Myocardial GRK2 expression and activity were also measured before CPB
      and just before weaning from CPB. RESULTS: Myocardial beta-AR signaling was
      significantly impaired after CPB and cardioplegic arrest during CABG. Cardiac
      GRK2 expression was not altered; however, there was a twofold increase in GRK2
      activity during CABG. There was an even greater elevation in cardiac GRK2
      activity in patients with severely depressed ventricular function. CONCLUSIONS:
      Increased myocardial GRK2 activity appears to be the primary mechanism of
      impaired beta-AR signaling during CABG with CPB and cardioplegic arrest. This may
      contribute to the greater need for inotropic support in patients with severe
      ventricular dysfunction. Strategies to inhibit activation of GRK2 during CABG may
      decrease morbidity in this patient population.

PMID- 18805159
TI  - Aprotinin in primary cardiac surgery: operative outcome of propensity score
      matched study.
AB  - BACKGROUND: Some recent multicenter series have questioned the safety of
      aprotinin in primary cardiac operations. We report a large, single-center
      experience with aprotinin therapy in primary cardiac operations and discuss the
      limitations and potential confounders of current treatment strategies. METHODS:
      We compared myocardial infarction, neurologic events, renal insufficiency, and
      operative death after first-time coronary or valve procedures, or both, in 3334
      patients treated with full-dose aprotinin with 3417 patients not treated with
      aprotinin who underwent operation between March 1998 and January 2007. Further
      analysis was performed for 341 propensity score-matched pairs. RESULTS: There
      were substantial differences between the groups. Aprotinin patients were higher
      risk on account of older age, unstable symptoms, poor ejection fraction,
      preoperative hemodynamic support, emergency/urgent operations, and combined
      coronary/valve operations. Postoperative bleeding and blood product transfusion
      were considerably reduced in aprotinin patients, as was median duration of
      mechanical ventilation. Aprotinin was neither a predictor of postoperative
      myocardial infarction, renal insufficiency, neurologic dysfunction, or operative
      death. Achieving parity between the groups by propensity score matching
      eliminated the elevated rates of postoperative renal insufficiency, neurologic
      dysfunction, and operative death observed in aprotinin patients in the unmatched
      comparison. These adverse outcomes were evenly distributed between matched
      groups. Conversely, blood transfusion had univariate associations with all
      adverse outcome measures. CONCLUSIONS: Full-dose aprotinin use was not associated
      with myocardial infarction, neurologic dysfunction, renal insufficiency, or death
      after coronary or valve operations. We observed less postoperative bleeding and
      blood product transfusion, and early extubation with the use of aprotinin.

PMID- 18805160
TI  - Invited commentary.

PMID- 18805161
TI  - Twenty-year experience with the St. Jude medical Biocor bioprosthesis in the
      aortic position.
AB  - BACKGROUND: The purpose of this study was to evaluate the long-term performance
      of the St. Jude Medical Biocor stented porcine prosthesis in the aortic position.
      METHODS: From January 1985 to December 1996, 455 patients admitted for aortic
      valve replacement were consecutively enrolled in this study. The mean age was
      72.5 +/- 9 years, 18 patients (3.5%) had had previous cardiac surgery, and
      coronary artery bypass grafting was performed in 171 patients (37.6%). Follow-up
      was complete in 99.6%; up to 21 years were covered. Actuarial event-free rates
      are given as mean +/- standard error and adverse events were classified according
      to the guidelines for reporting morbidity and mortality after cardiac valvular
      operations. RESULTS: Cumulative follow-up time was 3,321 patient-years with a
      mean follow-up of 8.2 years. The actuarial survival rate after 20 years was 9.4%
      +/- 2.8%. The actuarial rates for freedom from structural valve deterioration
      were 93.1% +/- 1.7% at 10 years, 88.4% +/- 3.5% at 15 years, and 70.3% +/- 10.9%
      at 20 years. The actuarial rates for freedom from reoperation due to structural
      valve deterioration were 91.9% +/- 1.6% at 10 years, 90.6% +/- 2.1% at 15 years,
      and 86.5% +/- 4.5% at 20 years. CONCLUSIONS: This study presents one of the
      largest series of St. Jude Medical Biocor aortic valves in the world. Results
      indicate an age-dependent risk of structural valve degeneration beginning as soon
      as 7 years postoperatively for patients below the age of 65 years, but show a low
      overall incidence of valve-related complications and excellent durability.

PMID- 18805162
TI  - Invited commentary.

PMID- 18805163
TI  - Effect of surgery for atrial fibrillation associated with mitral valve disease.
AB  - BACKGROUND: The purpose of this study is to evaluate the effect of surgery for
      atrial fibrillation (AF) associated with mitral valve disease. METHODS: From
      September 1994 to December 2006, 244 patients who underwent mitral valve surgery
      were enrolled in this study. The maze procedure or pulmonary vein isolation was
      concomitantly performed in 147 patients, while the remaining 97 patients were not
      surgically treated for AF. The patients were divided into 3 groups based on their
      cardiac rhythm at discharge from the hospital: the sinus group (108 patients),
      the intractable AF group (39 patients), and the untreated AF group (97 patients).
      The clinical features and late results of patients were compared among these
      groups. RESULTS: Early mortality rate was 0.7% and no major morbid events had
      occurred. Follow-up was completed in 95.6% of the patients and the mean follow-up
      period was 6.03 years. Actuarial survival was not significant between the sinus
      and AF groups. Actuarial freedom from thromboembolism at 5 and 10 years was 96.5%
      in the sinus group, 82.4% and 78.1%, respectively, in the intractable AF group,
      and 93.4% and 89.1%, respectively, in the untreated AF group; statistical
      significance was observed among the 3 groups (p = 0.01). By means of multivariate
      analysis, intractable AF was found to be the only risk factor for thromboembolism
      and other complications. CONCLUSIONS: Atrial fibrillation associated with mitral
      valve disease should be treated, because restoration of the sinus rhythm might
      lead to a lower incidence of thromboembolism and valve-related complications in
      the later period.

PMID- 18805164
TI  - Invited commentary.

PMID- 18805165
TI  - Minimally invasive surgical pulmonary vein isolation alone for persistent atrial
      fibrillation: preliminary results of epicardial atrial electrogram analysis.
AB  - BACKGROUND: Minimally invasive surgical pulmonary vein isolation has become an
      alterative therapy for lone atrial fibrillation. This study evaluated the effect
      of the procedure on persistent atrial fibrillation by epicardial atrial
      electrography. METHODS: Five consecutive patients with lone persistent atrial
      fibrillation were enrolled. Intraoperative electrophysiology tests were performed
      before and after minimally invasive surgical pulmonary vein isolation. Morphology
      of the recordings and atrial fibrillation cycle length were analyzed. RESULTS:
      Sixty sites were recorded in 5 patients. Three types of bipolar electrogram were
      recorded at these sites. After ablation, all electrograms changed into type I in
      pulmonary veins and proximal antra, and remained unchanged in all proximal left
      atria. Atrial fibrillation cycle length at the proximal left atrium was shorter
      than that at the pulmonary veins. Atrial fibrillation cycle length recorded at
      proximal left atrium sites correlated with atrial diameter. The atrial
      fibrillation cycle length of the left atrium increased from 143 +/- 11 to 170 +/-
      12 ms after pulmonary vein isolation. All 5 patients had atrial fibrillation
      immediately after the procedure and were treated with direct-current
      cardioversion and received amiodarone postoperatively. Freedom from atrial
      fibrillation was 100% at discharge and 60% at 6 months' follow-up. CONCLUSIONS:
      Ectopic foci outside the pulmonary veins play an important role in persistent
      atrial fibrillation. Minimally invasive surgical pulmonary vein isolation might
      not be sufficient for persistent atrial fibrillation termination. The pulmonary
      vein isolation procedure, however, slows atrial fibrillation and makes
      supplemental pharmacologic cardioversion effective.

PMID- 18805166
TI  - Invited commentary.

PMID- 18805167
TI  - Improved survival and decreasing incidence of adverse events with the HeartMate
      II left ventricular assist device as bridge-to-transplant therapy.
AB  - BACKGROUND: Pulsatile left ventricular assist devices (LVADs) are effective as
      bridge-to-transplant therapy, but they are limited by their large size and lack
      of durability. Smaller, more durable, continuous flow devices such as the
      HeartMate II LVAD are increasingly being used. The aim of this study is to report
      our single-center experience with this device as bridge-to-transplant therapy.
      METHODS: Overall, 47 patients received HeartMate II LVADs at our center from June
      2005 to July 2007; 32 as bridge to transplant, 7 as destination therapy, and 8 as
      exchange therapy for a failed HeartMate XVE. We reviewed our experience with the
      device as bridge-to-transplant therapy and report on patient survival and adverse
      events. RESULTS: The mean age of the bridge-to-transplant patients was 50.75 +/-
      13.78 years; 10 (31.3%) were female. The cause of the underlying disease was
      ischemic in 18 patients (56.3%), idiopathic in 11 (34.4%), myocarditis in 1
      (3.1%), postpartum cardiomyopathy in 1 (3.1%), and congenital heart disease in 1
      (3.1%). The mean duration of HeartMate II support was 193.2 +/- 139.9 days. At 30
      days after HeartMate II placement, the patient survival was 96.9% by Kaplan-Meier
      analysis; at 6 months (alive or transplanted), 86.9%. Major adverse events
      included bleeding requiring reexploration in 5 patients (15.6%), right
      ventricular failure requiring right ventricular assist device support in 2
      (6.3%), LVAD-related infections in 4 (12.5%), neurologic or thromboembolic events
      in 2 (6.3%), and gastrointestinal bleeding in 5 (15.6%). We noted one serious
      device malfunction (3.1%) resulting in the patient's death; in addition, 2
      patients experienced pump thrombosis (6.3%). CONCLUSIONS: Despite morbidity, use
      of the HeartMate II LVAD as bridge-to-transplant therapy is associated with
      excellent survival and low mortality rates. We found a marked decrease in
      morbidity related to right ventricular failure, to device-related infections, and
      to thromboembolic events. However, the requirements for anticoagulation therapy
      may be associated with increased mediastinal and gastrointestinal bleeding.
      Strategies to optimize anticoagulation therapy may further improve results for
      these critically ill patients.

PMID- 18805168
TI  - Body mass index and outcome after ventricular assist device placement.
AB  - BACKGROUND: The implantation of ventricular assist devices (VAD) is an
      established treatment for end-stage congestive heart failure. Extremes of body
      mass index (BMI) are associated with decreased survival after cardiac surgery.
      Many patients with congestive heart failure develop cardiac cachexia. In this
      study the association between BMI and outcomes after VAD implantation was
      investigated. METHODS: Consecutive patients (n = 590) who underwent VAD placement
      between 1996 and 2006 were divided into five groups based on BMI (kg/m2)
      quintiles (<20; 20-24; 25-29; 30-35; and >35). In a multivariate analysis
      adjusted for age, sex, diagnosis, emergency level, and type of device (left
      ventricular or biventricular assist device), procedural success (recovery,
      transplantation, or 30-day survival) and complications were analyzed. The best
      group was set as reference category for calculation of odds ratios. RESULTS: The
      groups with both extremes of BMI had the worst outcomes. The best procedural
      success was in the group with BMI 25 to 29 kg/m2. Underweight patients had
      similar survival rates to patients with normal weight. Overweight and obese
      patients did not have decreased survival. Extreme obesity at the time of VAD
      implantation showed elevated risk for postoperative death. There was no
      significant difference for BMI groups in the type of complications and cause of
      death. Cumulative survival curves for BMI category and overall VAD patient
      survival showed no significant differences. CONCLUSIONS: Cardiac cachexia need
      not be an exclusion criterion for VAD placement. Underweight patients appear to
      have benefit from mechanical support. Severely obese patients should be carefully
      selected before VAD placement.

PMID- 18805169
TI  - Extracellular matrix remodeling attenuated after experimental postinfarct left
      ventricular aneurysm repair.
AB  - BACKGROUND: Left ventricular aneurysm repair (LVAR) prevents congestive heart
      failure after myocardial infarction (MI). LV dilation after MI is related to
      postinfarct myocardial remodeling and leads to CHF. Because changes in matrix
      metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), and
      the physical properties of collagens are involved in myocardial remodeling, the
      effect of postinfarct LVAR on these factors was tested. METHODS: Rats with
      surgically induced MI, which did or did not receive postinfarct LVAR, were
      compared with each other and with controls. TIMP messenger RNA and protein
      expression, MMP gelatin zymography activity, and collagen fibrosis were measured
      in heart tissue. RESULTS: A threefold difference in the infarction area ratio was
      observed between samples of LVAs and of repaired LVAs. Compared with rats without
      LVAR, rats with repaired LVAs exhibited a higher percentage fractional shortening
      and significantly lower LV end-systolic and end-diastolic diameters. These
      salutary effects on LV diameter after LVAR were accompanied by a reversal of
      myocardial remodeling activity. After MI, TIMP expression decreased, MMP activity
      increased, and collagen fibrosis increased. After LVAR, TIMP expression
      increased, and MMP activity and collagen fibrosis decreased. These markers of
      remodeling activity changed significantly and approached preinfarct levels after
      LVAR. CONCLUSIONS: This study demonstrated that postinfarct LVAR prevents further
      congestive heart failure by attenuating myocardial remodeling in the LV and is
      thus indicated both to prevent heart failure and to reduce excessive postinfarct
      myocardial remodeling.

PMID- 18805170
TI  - Invited commentary.

PMID- 18805171
TI  - Increased mortality at low-volume orthotopic heart transplantation centers:
      should current standards change?
AB  - BACKGROUND: The Centers for Medicare and Medicaid Services (CMS) mandate that
      orthotopic heart transplantation (OHT) centers perform 10 transplants per year to
      qualify for funding. We sought to determine whether this cutoff is meaningful and
      establish recommendations for optimal center volume using the United Network for
      Organ Sharing (UNOS) registry. METHODS: We reviewed UNOS data (years 1999 to
      2006) identifying 14,401 first-time adult OHTs conducted at 143 centers.
      Stratification was by mean annual institution volume. Primary outcomes of 30-day
      and 1-year mortality were assessed by multivariable logistic regression (adjusted
      for comorbidities and risk factors for death). Sequential volume cutoffs were
      examined to determine if current CMS standards are optimal. Pseudo R2 and area
      under the receiver operating curve assessed goodness of fit. RESULTS: Mean annual
      volume ranged from 1 to 90. One-year mortality was 12.6% (n = 1,800). Increased
      center volume was associated with decreased 30-day mortality (p < 0.001).
      Decreased center volume was associated with increases in 30-day (odds ratio [OR]
      1.03, 95% confidence interval [CI]: 1.02 to 1.03, p < 0.001) and 1-year mortality
      (OR 1.01, 95% CI: 1.01 to 1.02, p = 0.03--censored for 30-day death). The
      greatest mortality risk occurred at very low volume centers (<or= 2 cases = 2.15
      times increase in death, p = 0.03). Annual institutional volume of fewer than 10
      cases per year increased 30-day mortality by more than 100% (OR 2.02, 95%CI: 1.46
      to 2.80, p < 0.001) and each decrease in mean center volume by one case per year
      increased the odds of 30-day mortality by 2% (OR 1.02, 95% CI: 1.01 to 1.03, p <
      0.001]. Additionally, centers performing fewer than 10 OHTs per year had
      increased cumulative mortality by Cox proportional hazards regression (hazard
      ratio 1.35, 95% CI: 1.14 to 1.60, p < 0.001). Sequential multivariable analyses
      suggested that current CMS standards may not be optimal, as all centers
      performing more than 40 transplants per year demonstrated less than 5% 30-day
      mortality. CONCLUSIONS: Annual center volume is an independent predictor of short
      term mortality in OHT. These data support reevaluation of the current CMS volume
      cutoff for OHT, as high-volume centers achieve lower mortality.

PMID- 18805172
TI  - Successful extracorporeal membrane oxygenation support after pulmonary
      thromboendarterectomy.
AB  - BACKGROUND: Pulmonary thromboendarterectomy (PTE) is the treatment of choice for
      patients with chronic thromboembolic pulmonary hypertension. However, some
      patients develop severe cardiorespiratory compromise soon after separating from
      cardiopulmonary bypass, either from early reperfusion pulmonary edema or right
      ventricular failure secondary to residual pulmonary hypertension. Since 2005 we
      have used venoarterial extracorporeal membrane oxygenation (ECMO) support in this
      group that has no other therapeutic option. We review our experience of early
      ECMO support in the severely compromised patient's post-PTE. METHODS: We
      conducted a retrospective review of all patients undergoing PTE from a single
      national referral center between August 2005 and August 2007. RESULTS: One
      hundred twenty-seven consecutive patients underwent PTE surgery. Seven patients
      (5.5%) had extreme cardiorespiratory compromise in the immediate postoperative
      period and required venoarterial ECMO support. Their mean age was 51.3 years with
      3 males. When compared with patients not requiring ECMO, these patients had
      significantly poorer hemodynamic indices before the operation with mean pulmonary
      artery pressure of 62 mm Hg versus 51 mm Hg (p = 0.02) and pulmonary vascular
      resistance of 907 dynes/sec/cm(-5) versus 724 dynes/s(-1)/cm(-5) (p < 0.02). Mean
      duration of support was 119 hours (49 to 359 hours). Five patients were
      successfully weaned from ECMO support (73%) and 4 left the hospital alive, giving
      a salvage rate of 57%. For those who did not require ECMO support, hospital
      mortality was 4.2%. CONCLUSIONS: Early venoarterial ECMO support has a role as
      rescue therapy post-PTE in patients with severe compromise who would probably
      otherwise die.

PMID- 18805173
TI  - Invited commentary.

PMID- 18805174
TI  - Targeted myocardial microinjections of a biocomposite material reduces infarct
      expansion in pigs.
AB  - BACKGROUND: Left ventricular (LV) remodeling after myocardial infarction (MI)
      commonly causes infarct expansion (IE). This study sought to interrupt IE through
      microinjections of a biocompatible composite material into the post-MI
      myocardium. METHODS: MI was created in 21 pigs (coronary ligation). Radiopaque
      markers (2-mm diameter) were placed for IE (fluoroscopy). Pigs were randomized
      for microinjections (25 injections; 2- x 2-cm array; 200 microL/injection) at 7
      days post-MI of a fibrin-alginate composite (Fib-Alg; fibrinogen, fibronectin,
      factor XIII, gelatin-grafted alginate, thrombin; n = 11) or saline (n = 10).
      RESULTS: At 7 days after injection (14 days post-MI), LV posterior wall thickness
      was higher in the Fib-Alg group than in the saline group (1.07 +/- 0.11 vs 0.69
      +/- 0.07 cm, respectively, p = 0.002). At 28 days post-MI, the area within the
      markers (IE) increased from baseline (1 cm2) in the saline (1.71 +/- 0.13 cm2, p
      = 0.010) and Fib-Alg groups (1.44 +/- 0.23 cm2, p < 0.001). However, the change
      in IE at 21 and 28 days post-MI was reduced in the Fib-Alg group (p=0.043 and
      p=0.019). Total collagen content within the MI region was similar in the saline
      and Fib-Alg groups (12.8 +/- 1.7 and 11.6 +/- 1.5 microg/mg, respectively, p =
      NS). However, extractable collagen, indicative of solubility, was lower in the
      Fib-Alg group than the saline group (59.1 +/- 3.5 vs 71.0 +/- 6.1 microg/mL, p =
      0.020). CONCLUSIONS: Targeted myocardial microinjection of the biocomposite
      attenuated the post-MI decrease in LV wall thickness and infarct expansion. Thus,
      intraoperative microinjections of biocompatible material may provide a novel
      approach for interrupting post-MI LV remodeling.

PMID- 18805175
TI  - Invited commentary.

PMID- 18805176
TI  - Enhanced perigraft angiogenesis prevents prosthetic graft infection.
AB  - BACKGROUND: Prosthetic vascular graft infection is an unsolved fatal complication
      after aortic surgery. We hypothesized that increased vascularity around a
      prosthetic graft may exert a preventive role against bacterial infection.
      METHODS: Eighty-three Fischer rats were divided into five groups according to the
      types of subcutaneously implanted prosthetic graft and granulocyte-colony
      stimulating factor (G-CSF) treatment. The groups G and C had gelatin hydrogel
      microspheres-incorporated graft (gel graft) with or without concomitant systemic
      administration of G-CSF (50 microg/kg), respectively. The groups FG and F had the
      gel graft impregnated with 100 mug of basic fibroblast growth factor (bFGF) with
      or without systemic G-CSF. The group N received untreated grafts. Seven days
      after graft implantation, broth containing methicillin-sensitive Staphylococcus
      aureus (4.0 x 10(3) colony-forming units) was inoculated onto the graft. All the
      grafts and the surrounding tissues were explanted 2 days later. Quantitative
      culture for methicillin-sensitive Staphylococcus aureus from the grafts and
      histologic assessment for capillary number in the tissue were performed. RESULTS:
      Positive infection rates in the groups N, C, and G were 34.7%, 30.4%, and 15.3%,
      respectively; whereas those were zero in the F and FG groups. Tissue around the
      grafts demonstrated significantly higher number of capillaries in the groups F
      and FG compared with the groups C and G. The number of bacterial colonies
      inversely correlated with the number of capillaries around the implanted graft (r
      = -0.32, p < 0.05). CONCLUSIONS: Basic fibroblast growth factor incorporated into
      a prosthetic graft with or without systemic G-CSF can induce angiogenesis around
      the graft and prevent prosthetic graft infection.

PMID- 18805177
TI  - Invited commentary.

PMID- 18805178
TI  - Cyclosporine preserves mitochondrial morphology after myocardial
      ischemia/reperfusion independent of calcineurin inhibition.
AB  - BACKGROUND: Opening of the mitochondrial permeability transition pore (MPTP) has
      been shown to contribute to myocardial ischemia/reperfusion injury. We sought to
      demonstrate that the myocardial protective effect of inhibiting MPTP opening with
      cyclosporine A (CsA) results in stabilization of mitochondrial morphology and is
      independent of CsA-induced calcineurin inhibition. METHODS: Thirty-seven rabbits
      were divided into three groups: control (n = 15), CsA (MPTP and calcineurin
      inhibitor, n = 12), or FK506 (calcineurin inhibitor, n = 10). Each group received
      a 1-hour infusion of either a saline vehicle, 25 mg/kg CsA or 1 mg/kg FK506. All
      animals underwent 30 minutes of regional ischemia and 3 hours of reperfusion.
      Myocardial infarct size was determined using Evans blue dye and
      triphenyltetrazolium chloride. In situ oligo ligation was used to assess
      apoptotic cell death. Transmission electron microscopy was used to quantitatively
      evaluate morphologic differences in the mitochondria between groups. RESULTS:
      Infarct size in the CsA group (39% +/- 3%) was significantly reduced compared
      with the control group (60% +/- 2%, p < 0.001) and FK506 group (55% +/- 3%, p =
      0.001). Apoptotic cell death was also attenuated in the CsA group (1.2% +/- 0.5%)
      compared with the control group (4.3% +/- 0.8%, p = 0.01) and FK506 group (4.1%
      +/- 0.9%, p = 0.05). Transmission electron microscopy revealed a preservation of
      normal mitochondrial morphology and a reduction in the percentage of disrupted
      mitochondria in the CsA group (20% +/- 7%) compared with the control group (53%
      +/- 12%) and FK506 group (47% +/- 9%). CONCLUSIONS: Cyclosporine A-induced MPTP
      inhibition preserves mitochondrial morphology after myocardial
      ischemia/reperfusion and limits myocyte necrosis and apoptosis. These effects are
      independent of calcineurin inhibition.

PMID- 18805179
TI  - Invited commentary.

PMID- 18805180
TI  - Should we address the neopulmonic valve? Significance of right-sided obstruction
      after surgery for transposition of the great arteries and coarctation.
AB  - BACKGROUND: The combination of transposition of the great arteries and
      coarctation of the aorta (TGA/CoA) presents a surgical challenge. We have adopted
      a concurrent aortic arch repair and arterial switch operation with excellent
      results. These patients tend to have a small aortic (ie, neopulmonary) annulus.
      This study evaluates the significance of right-sided obstruction after single
      stage repair of TGA/CoA. METHODS: Between May 1991 and May 2006, 53 patients with
      TGA/CoA or Taussig-Bing/CoA (n = 20; 38%) underwent a complete single-stage
      repair. Surgical technique involved the arterial switch operation and ventricular
      septal defect closure when present in 51 patients (96%). The aortic arch was
      enlarged in 36 patients (75%) with patch augmentation. Two patients (4%)
      underwent the augmentation of the right ventricular outflow tract (RVOT) at the
      first operation. RESULTS: There was one hospital death (operative mortality,
      1.9%) and one late death. The difference between the preoperative aortic and
      pulmonary annulus was significant (6.7 vs 10.4 mm, p < 0.001). The peak pressure
      gradient across the proximal RVOT at discharge was 16 +/- 16 mm Hg (range, 0 to
      62 mm Hg). There have been six reoperations (11%) and four catheter interventions
      (7.5%) for right-sided obstruction. Freedom from reintervention/reoperation for
      right-sided obstruction at 1, 5, and 10 years is 95%, 87%, and 80%, respectively.
      CONCLUSIONS: Neonatal single-stage repair for TGA/CoA achieves excellent survival
      without transannular patch repair at the first operation. Although some of the
      patients have pressure gradient across the RVOT, these lesions were amenable to
      reintervention with minimal morbidity.

PMID- 18805181
TI  - Development of the pulmonary arteries after the Norwood procedure: comparison
      between Blalock-Taussig shunt and right ventricular-pulmonary artery conduit.
AB  - BACKGROUND: The Norwood-Sano procedure for hypoplastic left heart syndrome (HLHS)
      has been associated with improved postoperative hemodynamics and outcome. This
      study compared the effect of a Blalock-Taussig shunt with right ventricular
      pulmonary artery (RV-PA) conduit before bidirectional Glenn on the development of
      the PAs. METHODS: Between January 2000 and June 2007, 42 patients with HLHS
      underwent bidirectional Glenn: 19 (mean age, 7 +/- 1.5 months) had a Blalock
      Taussig shunt (3.5 mm in 15; and 4 mm in 4); 23 patients (mean age, 5 +/- 1
      month) had RV-PA conduit (5-mm tube). Patients underwent postoperative cardiac
      catheterization and echocardiograms. RESULTS: Total PA (Nakata) index was 192 +/-
      10 mm2/m2 in the Blalock-Taussig group and 238 +/- 18 mm2/m2 in the RV-PA conduit
      group (p = 0.03). In the RV-PA conduit patients, the left and right PAs had
      comparable diameters. In the Blalock-Taussig group, the left PA was smaller than
      the right (p = 0.02). The mean PA pressure at the end of the operation was 14 +/-
      2 mm Hg in the Blalock-Taussig group and 11 +/-1 mm Hg in the RV-PA conduit group
      (p = 0.06). Persistent pleural effusion occurred in 4 Blalock-Taussig patients
      (21%) and in 1 (4%) with RV-PA conduit (p < 0.05). Postoperative arterial oxygen
      saturation was 80% +/- 2% in the RV-PA conduit group and 74% +/- 2% in the
      Blalock-Taussig group (p < 0.05). CONCLUSIONS: The Norwood procedure with RV-PA
      conduit may have favorable effects on the development of the PA due to even
      distribution of pulmonary blood flow.

PMID- 18805182
TI  - Outcomes of reparative and transplantation strategies for multilevel left heart
      obstructions with mitral stenosis.
AB  - BACKGROUND: Conventional management for multilevel left heart obstructions and
      mitral stenosis (Shone's complex) involves multiple operations that carry
      additive risks. This study reviews our experience with reconstructive and
      transplantation approaches for Shone's complex. METHODS: Between 1987 and 2007,
      43 patients with mitral stenosis and one or more left-sided obstructions were
      identified: supramitral ring (n = 13), subaortic stenosis (n = 25), aortic
      stenosis (n = 24), hypoplastic arch (n = 20), and coarctation (n = 38). Thirty
      patients underwent a staged reparative approach, including 27 mitral and 51 left
      ventricular outflow tract operations. Thirteen patients were referred for
      transplantation. Patients with severe hypoplasia of the left ventricle were
      excluded. RESULTS: There was one in-hospital death (2.5%) and six late deaths
      (14.2%). Actuarial 5- and 10-year survival for staged surgical and
      transplantation was 88% vs 61.3% and 83.1% vs 61.3% (p = 0.035). At a mean follow
      up of 7.9 years, freedom from mitral reoperation was 83.3% and freedom from
      reoperation for subaortic stenosis was 78.0%. Wait-list mortality was 13.3% (2 of
      13). Wait-list time exceeding 90 days was an incremental risk factor for death
      after transplantation (p = 0.005). CONCLUSIONS: Despite the challenges of a
      reparative strategy for Shone's complex, favorable survival and durability
      outcomes can be expected. Heart transplantation, although avoiding the pitfalls
      of staged repair, confers increased risks from ongoing physiologic derangements
      due to uncorrected left heart inflow and outflow obstructions during the wait for
      donor heart availability.

PMID- 18805183
TI  - Dynamics of human myocardial progenitor cell populations in the neonatal period.
AB  - BACKGROUND: Pluripotent cardiac progenitor cells resident in myocardium offer a
      potentially promising role in promoting recovery from injury. In pediatric
      congenital heart disease (CHD) patients, manipulation of resident progenitor
      cells may provide important new approaches to improving outcomes. Our study goals
      were to identify and quantitate populations of progenitor cells in human neonatal
      myocardium during the early postnatal period and determine the proliferative
      capacity of differentiated cardiac myocytes. METHODS: Immunologic markers of cell
      lineage (stage-specific embryonic antigen 4 [SSEA-4], islet cell antigen 1
      [Isl1], c-kit, Nkx2.5, sarcoplasmic reticulum calcium-regulated ATPase type 2
      [SERCA2]) and proliferation (Ki67) were localized in right ventricular biopsies
      from 32 CHD patients aged 2 to 93 days. RESULTS: Neonatal myocardium contains
      progenitor cells and transitional cells expressing progenitor and differentiated
      myocyte marker proteins. Some cells expressed the pluripotent cell marker c-kit
      and also coexpressed the myocyte marker SERCA2. Multipotent progenitor cells,
      identified by the expression of Isl1, were found. Ki67 was expressed in some
      myocytes and in nonmyocyte cells. A few cells expressing SSEA-4 and Isl1 were
      observed during the early postnatal period. Cells expressing c-kit, the
      premyocyte marker Nkx2.5, and Ki67 were found throughout the first postnatal
      month. A progressive decline in cell density during the first postnatal month was
      observed for c-kit+ cells (p = 0.0013) and Nkx2.5+ cells (p = 0.0001). The
      percentage of cells expressing Ki67 declined during the first 3 postnatal months
      (p = 0.0030). CONCLUSIONS: Cells in an incomplete state of cardiomyocyte
      differentiation continue to reside in the infant heart. However, the relative
      density of progenitor cells declines during the first postnatal month.

PMID- 18805184
TI  - Invited commentary.

PMID- 18805185
TI  - Morphologic spectrum of ventriculoarterial connection in hearts with double inlet
      left ventricle: implications for surgical procedures.
AB  - BACKGROUND: This study was conducted to determine a morphologic spectrum of
      ventriculoarterial connection in double inlet left ventricle and implications for
      surgical procedures. METHODS: Examined were 54 autopsied heart specimens and 43
      consecutive clinical patients. RESULTS: The hypoplastic and incomplete
      morphologic right ventricle was located leftward to the dominant ventricle in 62
      and adjacent to the right atrium in 35. Common patterns were seen in 46 of 62
      (74%) with the right ventricle leftward (discordant ventriculoarterial connection
      with the aorta left-anteriorly located ["SLL" type]) and in 28 of 35 (80%) with
      the right ventricle rightward (either the normally connected great arteries in 13
      or discordant connections with the aorta right-anteriorly located in 15). In the
      remaining 23 hearts, the great arteries were unusually oriented in 7, the outlet
      septum was malaligned in 9, or the pulmonary trunk was atretic in 7. In those
      with malalignment, the ventriculoarterial connections were double outlet from the
      right ventricle, from the left ventricle, or were transitional with overriding of
      one of the great arteries. In the clinical series, 19 of 35 patients (54%) in
      whom the aorta arose from the morphologically right ventricle underwent either
      myectomy to enlarge the interventricular communication or a Damus-Kaye-Stansel
      anastomosis was fashioned to treat existing or potential subaortic stenosis. Only
      1 of 8 patients with the aorta arising from the dominant ventricle needed similar
      surgical procedures. CONCLUSIONS: Ventriculoarterial connection in double inlet
      left ventricle demonstrated a morphologic spectrum and needs precise recognition
      to provide an unobstructed ventricular outflow after operation.

PMID- 18805186
TI  - Invited commentary.

PMID- 18805187
TI  - Is the morphologic mitral valve in discordant atrioventricular connections always
      normal?
AB  - BACKGROUND: The purpose of this study was to determine structural features and
      variations in the mitral valve guarding inflow of the morphologic left ventricle
      in hearts with discordant atrioventricular connections. METHODS: Morphologic
      investigation was carried out on the inlet valve to the morphologic left
      ventricle in 48 autopsied specimens with this particular entity of malformation.
      RESULTS: The tension apparatus was straddling to the morphologic right ventricle
      in 2. Another 34 hearts had a bifoliate valve and the papillary muscles
      abnormally oriented; a solitary papillary muscle in 3, two papillary muscles but
      deviated in 5, one of two papillary muscles being dysmorphic in 9, and three or
      more papillary muscles in 17. The origin of these papillary muscles was
      frequently deviated. In 5 hearts with a trifoliate or quadrifoliate valve,
      multiple papillary muscles were also the case. One of these had thick leaflets, a
      part of which was adherent to a membranous flap around the ventricular septal
      defect as well as to subpulmonary fibrous tissue tags. Eventually, the valve was
      comparable with the mitral valve seen in the normally structured heart in only 7
      hearts (15%). There was no obvious correlation noted between the presence of
      abnormality in the mitral valve and that in the tricuspid valve. CONCLUSIONS:
      Architectural abnormalities are not rare in the morphologic mitral valve in this
      setting. The valvar structure needs precise recognition.

PMID- 18805188
TI  - Management of pulmonary artery sling associated with tracheal stenosis.
AB  - BACKGROUND: Pulmonary artery sling is often associated with congenital tracheal
      stenosis and intracardiac anomalies. This study examines the influence of
      concomitant anomalies and individual surgical procedures. METHODS: Between 1984
      and 2006, 31 patients underwent surgical repair of pulmonary artery sling
      (median, 6 months; range, 29 days to 9 years). Twenty-eight of them underwent
      left pulmonary artery reimplantation and tracheoplasty, whereas the remaining 3
      received only left pulmonary reimplantation. The first 4 patients with long
      segment tracheal stenosis were treated with a costal cartilage graft and the next
      19 with slide tracheoplasty. Five patients underwent tracheal resection with end
      to-end anastomosis. Associated cardiac anomalies in 10 patients were repaired
      concomitantly with left pulmonary artery reimplantation and tracheoplasty.
      RESULTS: Two patients died early of low-output syndrome (n = 1) and ventricular
      arrhythmia (n = 1). Follow-up was complete in all patients (median, 4.6 years)
      with 3 late deaths arising from residual tracheal stenosis or pulmonary
      hypertension. Two survivors with a costal cartilage graft remain free of
      respiratory problems. Of 16 survivors who underwent slide tracheoplasty, 9 who
      did not have tracheostomy are fully active and 7 had tracheostomy to treat
      tracheomalacia and granulation. Among 5 survivors of tracheal resection, 4 are
      doing well without tracheostomy. Echocardiography showed that the left pulmonary
      artery was patent in all assessed patients, but 1 required balloon arterioplasty.
      CONCLUSIONS: Left pulmonary reimplatation with simultaneous repair of tracheal
      stenosis and intracardiac anomalies results in low operative mortality and
      satisfactory left pulmonary artery patency. However, the management of younger
      infants with tracheoplasty for long segment stenosis involving carina or complex
      cardiac anomalies remains challenging.

PMID- 18805189
TI  - Clinical application of direct bronchial ultrasound to visualize and determine
      endobronchial tumor margins for surgical resection.
AB  - PURPOSE: We describe the first experience of direct bronchial (epi-bronchial)
      ultrasound to visualize and determine the endobronchial tumor margins for
      surgical resection. DESCRIPTION: An ultrasound probe was applied onto the
      membranous portion of the right main bronchus directly over a pedunculated tumor.
      The tumor was visualized due to the water content, with a total loss of signal
      (air-tumor interface) at the tumor edge. A sterile marker was used to outline the
      air-tumor interface. EVALUATION: Traditionally, surgical technique involves
      palpation of the tumor with an incision to inspect the endobronchial lumen
      determining the position of the pedicle, thus estimating the amount of airway to
      resect. Using direct bronchial ultrasound, the right main palpated margin was 0.5
      cm proximal to the ultrasound margin, which correctly identified the tumor
      margin. The upper lobe palpated margin was 1 cm proximal to the ultrasound
      margin, which correctly identified the tumor margin. In the intermediate
      bronchus, the palpated and ultrasound margin were the same and correct.
      CONCLUSIONS: By using the air-tumor interface, epi-bronchial ultrasound scanning
      can accurately demarcate the base of endobronchial tumors for surgical resection
      and reconstruction.

PMID- 18805190
TI  - Invited commentary.

PMID- 18805191
TI  - Performance of a 3-bladed propeller pump to provide cavopulmonary assist in the
      failing Fontan circulation.
AB  - PURPOSE: We hypothesized that a propeller pump design would function optimally to
      provide cavopulmonary assist in a univentricular Fontan circulation. DESCRIPTION:
      The hydraulic and hemolysis performance of a rigid three-bladed propeller
      prototype (similar to a folding propeller design) was characterized. Pressure and
      flow measurements were taken for flow rates of 0.5 to 3 liters per minute (LPM)
      for 5,000 to 7,000 revolutions per minute (RPM) using a blood analog fluid.
      Hemolysis testing was performed using fresh bovine blood for 2 LPM at 6,000 RPM
      for a 6-hour duration. EVALUATION: The prototype performed well over the design
      operating range by producing a pressure rise of 5 to 50 mm Hg. Plasma free
      hemoglobin concentration remained less than 15 mg/dL. The normalized index of
      hemolysis peaked during the first hour, and then remained less than 10 mg/dL
      thereafter. CONCLUSIONS: A propeller pump has the pressure-flow characteristics
      and minimal risk of hemolysis and venous pathway obstruction which make it ideal
      for temporary cavopulmonary assist. This type of device has the potential to
      provide a new therapeutic option for patients with failing univentricular Fontan
      physiology as a bridge-to-recovery or transplantation.

PMID- 18805192
TI  - Veno-venous extracorporeal membrane oxygenation in surgery for bronchial repair.
AB  - Single-lung ventilation using a double-lumen endobronchial tube is often
      performed for surgical procedures involving the thorax. Tracheobronchial rupture
      during use of an endobronchial tube is an uncommon and serious complication. We
      present the case of a patient undergoing a right pneumonectomy who experienced a
      bronchial rupture due to a double-lumen endobronchial tube. Institution of veno
      venous extracorporeal membrane oxygenation allowed removal of the endobronchial
      tube, and the repair was successfully performed. We hope that this information
      can provide further insight into the management of such a complication.

PMID- 18805193
TI  - Quadrilateral space syndrome: a rare complication of thoracic surgery.
AB  - We report a case of quadrilateral space syndrome related to thoracic surgery. A
      21-year-old man underwent video-assisted thoracic surgery for a left-sided
      pneumothorax. After the operation, he presented with difficulties in left arm
      abduction and paresthesia over the lateral aspect of the shoulder and upper arm.
      Deltoid muscle atrophy and tenderness over the quadrilateral space were also
      observed. On further examination, he was diagnosed with isolated paralysis of the
      axillary nerve, the so-called quadrilateral space syndrome. This is a rare
      complication, but it interferes with the activities of daily living, and thus one
      should pay attention to this syndrome.

PMID- 18805194
TI  - Progressive Dyspnea After CABG: Complication of Retained Epicardial Pacing Wires.
AB  - We report a case of progressive dyspnea and recurrent pneumonia after uneventful
      coronary artery bypass graft surgery caused by migration of retained epicardial
      pacing wires into the right upper lobe of the lung. Removal of the wires by open
      thoracotomy resulted in significant improvement in dyspnea and near complete
      resolution of the bronchiectasis and consolidation.

PMID- 18805195
TI  - Pulmonary artery sarcoma mimicking a pulmonary artery aneurysm.
AB  - Pulmonary artery sarcoma is an uncommon neoplasm, and its clinical and
      radiological presentation usually simulates chronic thromboembolic disease. We
      present the case of a 77-year-old woman admitted with dyspnea, chest pain, and
      hemoptysis. A chest computed tomographic scan showed moderate right-sided pleural
      effusion and a saccular dilatation of the interlobar portion of the right
      pulmonary artery, which was filled with contrast and surrounded by an irregular
      soft-tissue attenuation mass, suggesting a ruptured pulmonary artery aneurysm.
      The patient was operated on. Intraoperatively, a pseudoaneurysm and a solid mass
      were identified within the oblique fissure around the interlobar artery.
      Therefore, a right pneumonectomy was performed. Definitive pathologic examination
      was consistent with pulmonary artery sarcoma. The patient had a good outcome and
      is free of disease 2 years after surgery.

PMID- 18805196
TI  - A novel approach to positron emission tomography in lung cancer.
AB  - 18F-fluorodeoxyglucose positron emission tomography-computed tomography is
      integral to the staging of lung cancer. We describe the combined use of
      diagnostic preoperative 18F-fluorodeoxyglucose positron emission tomography
      computed tomography, intraoperative 18F-fluorodeoxyglucose handheld gamma probe
      detection, and immediate postoperative 18F-fluorodeoxyglucose positron emission
      tomography-computed tomography patient and specimen imaging for improved staging
      and determination of adequacy of mediastinal lymph node dissection.

PMID- 18805197
TI  - Prolonged extracorporeal membrane oxygenation and circulatory support as bridge
      to lung transplant.
AB  - A 38-year-old man with progressive alveolitis secondary to polymyositis was
      treated for 52 days with venovenous and venoarterial extracorporeal membrane
      oxygenation as a bridge to bilateral lung transplantation. The patient survived,
      despite multiple complications, and is now back home with good pulmonary
      function. He is working part-time nearly 3 years post-transplant. This case shows
      that long-term extracorporeal lung assist is a viable but demanding alternative
      for bridging patients to pulmonary transplantation. This case also shows that
      right ventricular failure necessating conversion to veno-arterial assist does not
      necessarily predict right ventricular failure post-transplant.

PMID- 18805198
TI  - Intrapulmonary localized fibrous tumor of the lung: a very unusual presentation.
AB  - Most localized fibrous tumors arise from the visceral pleura on a stalk and
      project into the pleural cavity in a pedunculated manner. The origin of the
      tumors is now believed not to be mesothelial but rather submesothelial, based on
      studies using conventional histology, immunohistochemistry, and ultrastructural
      analysis. While inward tumor growth into the lung parenchyma with attachment to
      the pleura is uncommon, the tumor with an entirely pulmonary location is
      extremely rare. We present here a rare case of entirely intrapulmonary localized
      fibrous tumor (ie, localized fibrous tumor of the lung), and we review the
      pertinent literature.

PMID- 18805199
TI  - Inflammatory myofibroblastic tumor mimicking anterior mediastinal malignancy.
AB  - Inflammatory myofibroblastic tumor arising in the anterior mediastinum is rare. A
      58-year-old woman had an anterior mediastinal mass invading the sternum,
      pericardium, and pleura. It was completely resected and found to be an
      inflammatory myofibroblastic tumor. The patient was well and had no recurrence 6
      months after surgery.

PMID- 18805200
TI  - Inflammatory myofibroblastic tumor presenting with esophageal obstruction and an
      inflammatory syndrome.
AB  - Inflammatory myofibroblastic tumor is a rare neoplasm of intermediate malignant
      potential. Although inflammatory myofibroblastic tumor occurs at multiple
      anatomic locations, an esophageal lesion is extremely rare. We describe a 43-year
      old man who presented with severe dysphagia and an inflammatory syndrome,
      secondary to esophageal inflammatory myofibroblastic tumor. The patient was
      treated successfully with esophagectomy and remains disease free at 1 year. This
      case illustrates the complexities involved in managing a large esophageal
      myofibroblastic tumor and highlights that esophagectomy, rather than enucleation,
      should be the treatment of choice.

PMID- 18805201
TI  - Stented esophageal transfixion injury.
AB  - Esophageal perforation is a rare, but life-threatening condition with a mortality
      rate ranging between 10% and 40%. It can happen at the level of the cervical,
      intrathoracic, or intra-abdominal segment. It usually occurs as a result of
      iatrogenic injury after endoscopic procedures or as a spontaneous rupture. It is
      seen less frequently in trauma after gunshot or stab wounds. Stenting of the
      esophagus after iatrogenic perforation is well documented in the literature, but
      yet it is to be published for management of penetrating injury. We report a case
      of esophageal perforation with a wooden fence post treated successfully with a
      covered esophageal stent.

PMID- 18805202
TI  - Early aortic bioprosthetic valve deterioration in an octogenarian.
AB  - We experienced extremely early aortic bioprosthetic valve deterioration with
      leaflet calcification and stiffening 2 1/2 years after aortic valve replacement
      in a female octogenarian. We could not identify the possible reason for this
      devastating complication; however, daily calcium supplement consumption may play
      a role of acceleration of calcium deposition in the leaflets of implanted
      bioprosthetic heart valves.

PMID- 18805203
TI  - Simultaneous rupture of the mitral and tricuspid valves with left ventricular
      rupture caused by blunt trauma.
AB  - To date, we believe that only 8 patients with simultaneous rupture of the mitral
      and tricuspid valves caused by blunt chest trauma have been reported. The correct
      diagnosis of this condition during the initial assessment is difficult and often
      delayed. Surgical experience with this condition has been quite limited. We
      present a unique case of atrioventricular valve rupture, combined with left
      ventricular rupture and a brief review of the relevant literature.

PMID- 18805204
TI  - Flow impeding fungal thrombus in the ascending aorta.
AB  - Mycotic endoaortitis is a rarely occurring infectious entity with an extremely
      high mortality rate. We report an uncommon case of Phialemonium endoaortits with
      its management. This large fungal thrombus in the ascending aorta caused
      significant impediment to the blood flow.

PMID- 18805205
TI  - Minimally invasive epicardial left atrial ablation and appendectomy for
      refractory atrial tachycardia.
AB  - Surgical removal or epicardial radiofrequency ablation of the left atrial
      appendage (LAA) is occasionally required when endocardial ablations fail. We
      report a modified minimally invasive surgical approach for elimination of
      recurrent atrial arrhythmias arising from the LAA, including both radiofrequency
      ablation and appendectomy. Ablation of the LAA base was performed using the
      Medtronic Cardioblate bipolar radiofrequency device (Medtronic, Minneapolis, MN),
      and left atrial appendectomy was then completed using the EndoGIA stapling system
      (US Surgical, Norwalk, CT). This procedure successfully isolated and removed the
      tachycardia focus, and normal sinus rhythm was restored. Elimination of LAA
      arrhythmias using a combination of epicardial radiofrequency ablation and
      appendectomy ensures electrical isolation while minimizing surgical invasiveness.

PMID- 18805206
TI  - Norwood procedure combined with the Starnes procedure.
AB  - We describe the case of 6-day-old baby girl with congenitally corrected
      transposition of the great arteries, Ebstein anomaly with severe tricuspid valve
      regurgitation, aortic atresia, hypoplastic aortic arch, and patent ductus
      arteriosus. She underwent Starnes procedure combined with the Norwood procedure.
      Postoperative echocardiography demonstrated good left ventricular function,
      reduced size of the right ventricle, and an unobstructed aortic arch. She was
      discharged and is currently awaiting a bidirectional Glenn operation.

PMID- 18805207
TI  - Coronary artery complications in infective endocarditis.

PMID- 18805208
TI  - Coronary arteriovenous fistula with aneurysm formation.

PMID- 18805209
TI  - Giant aortic aneurysm as a rare cause of superior vena cava syndrome.

PMID- 18805210
TI  - Sternal plating to prevent malunion of transverse sternotomy in lung
      transplantation.
AB  - Sternal malunion can be a significant cause of morbidity in double-lung
      transplantation when it is performed through a thoracosternotomy or clamshell
      incision. Some patients experience increased pain with malunion and have delayed
      or decreased functional recovery. We propose a method of sternal plating to
      decrease the incidence of sternal malunion encountered with this incision. The
      transverse sternotomy can be rigidly fixed with two titanium interlocking plates
      during chest closure, a procedure that offers the potential for timely and
      consistent union of the sternum. The interlocking plate configuration also
      affords a unique quality to this closure; a pin securing the two plates can be
      quickly released allowing expedient access to mediastinal structures if emergent
      re-entry is necessary.

PMID- 18805211
TI  - Transecting the aorta to close the aortic prosthetic valve paravalvular space.
AB  - The residual aortic prosthetic valve paravalvular space beneath the left coronary
      artery is very difficult and risky to repair. To improve visualization of this
      area, we transected the ascending aorta and mobilized both the aortic root and
      the left coronary artery from the surrounding tissue. Subsequently, we retracted
      the left coronary artery aside and pulled the posterior aortic root upwards. This
      maneuver has provided enough space for the safe placement of stitches and the
      closure of the paraprosthetic defect in this very delicate area.

PMID- 18805212
TI  - Early and midterm outcomes of folding valvuloplasty without leaflet resection for
      myxomatous mitral valve disease.
AB  - We performed 46 cases of folding valvuloplasty without leaflet resection for
      myxomatous mitral regurgitation (MR) between August 2004 and December 2006.
      Operative mortality was zero. No patient had greater than grade 1 MR or systolic
      anterior motion on intraoperative transesophageal echocardiography. In median of
      17 months' follow-up, no patient had a reoperation for recurrent MR. Among 31
      patients who had an echocardiographic follow-up, 28 had zero or grade 1 MR, 3 had
      grade 2 MR, and no patient had grade 3/4 MR. Folding valvuloplasty is a simple
      and effective technique for selected types of myxomatous MR with favorable
      outcomes and midterm echocardiographic findings.

PMID- 18805213
TI  - Intravascular ultrasound imaging as applied to the aorta: a new tool for the
      cardiovascular surgeon.
AB  - Intravascular ultrasound is a novel endovascular imaging technology that is
      useful as an imaging tool for diagnosis and treatment of arterial and venous
      pathologies. Intravascular ultrasound is particularly useful as a decision-making
      tool in the endovascular management of vascular pathologies. Recently the aorta
      has become increasingly amenable to endovascular technology, and with the advent
      of intravascular ultrasound detailed imaging, using intravascular ultrasound
      permits the diagnosis and endovascular management of various complex aortic
      pathologies affecting the abdominal and thoracic aorta. Various aortic
      pathologies including thoracic and abdominal aortic aneurysms, type B
      dissections, penetrating aortic ulcers, coarctation of the aorta, and many other
      aortic pathologies, which were once only amenable by open surgical repair are
      increasingly being managed with endoluminal technology. As experience develops
      with this technology, more complex aortic pathologies would become readily
      amenable to advanced endovascular interventions.

PMID- 18805214
TI  - Hypothermic circulatory arrest in the treatment of descending thoracic and
      thoracoabdominal aortic disease.

PMID- 18805215
TI  - Vacuum for pediatric post-sternotomy mediastinitis: the role of laser Doppler
      velocimetry in the establishment of adequate subatmospheric pressure intensity.

PMID- 18805217
TI  - Perfusion of the lower part of the body during open aortic arch surgery.

PMID- 18805219
TI  - Beating heart cardioscopy: on-pump or off-pump?

PMID- 18805220
TI  - New discussion on an old subject: proximal anastomosis markers in coronary bypass
      surgery.

PMID- 18805222
TI  - Permanent pacemaker implantation after isolated aortic valve replacement.

PMID- 18805223
TI  - Preface. Contemporary dental and maxillofacial imaging.

PMID- 18805224
TI  - The evolution and application of dental maxillofacial imaging modalities.
AB  - During the last decades, an exciting new array of imaging modalities, such as
      digital imaging, CT, MRI, positron emission tomography, and cone-beam CT (CBCT),
      has provided astounding new images that continually contribute to the accuracy of
      diagnostic tasks of the maxillofacial region. The most recent, cone-beam imaging,
      is gaining rapid acceptance in dentistry because it provides cross-sectional
      imaging that is often a valuable supplement to intraoral and panoramic
      radiographs. The information content in such examinations is high and the dose
      and costs are low. The increasing trend toward the use of CBCT in dental offices
      may be expected to result in improved diagnosis, but with increased patient dose
      and health care costs. Using CBCT as a secondary imaging tool helps optimize
      health-to-risk ratio.

PMID- 18805225
TI  - What is cone-beam CT and how does it work?
AB  - This article on x-ray cone-beam CT (CBCT) acquisition provides an overview of the
      fundamental principles of operation of this technology and the influence of
      geometric and software parameters on image quality and patient radiation dose.
      Advantages of the CBCT system and a summary of the uses and limitations of the
      images produced are discussed. All current generations of CBCT systems provide
      useful diagnostic images. Future enhancements most likely will be directed toward
      reducing scan time; providing multimodal imaging; improving image fidelity,
      including soft tissue contrast; and incorporating task-specific protocols to
      minimize patient dose.

PMID- 18805226
TI  - Cone beam tomographic imaging anatomy of the maxillofacial region.
AB  - Multiplanar imaging is a fairly new concept in diagnostic imaging available with
      a number of contemporary imaging modalities such as CT, MR imaging, diagnostic
      ultrasound, and others. This modality allows reconstruction of images in
      different planes (flat or curved) from a volume of data that was acquired
      previously. This concept makes the diagnostic process more interactive, and
      proper use may increase diagnostic potential. At the same time, the complexity of
      the anatomical structures on the maxillofacial region may make it harder for
      these images to be interpreted. This article reviews the anatomy of maxillofacial
      structures in planar imaging, and more specifically cone-beam CT images.

PMID- 18805227
TI  - Application of cone-beam CT in the office setting.
AB  - The decision to incorporate cone-beam CT (CBCT) into a dental practice is one
      that requires serious consideration and careful planning. In the early days of
      the technology, fewer sources of information existed and a community of users
      often shared ideas and prompted the advancement of the products. Office-based
      CBCT has advanced significantly since that time. It has often been described as
      the "gold standard" for imaging the oral and maxillofacial area and will become a
      part of the everyday life of most practices in the coming decades.

PMID- 18805228
TI  - Computer-aided dental implant planning.
AB  - Computer-aided dental implant planning increases the predictability of replacing
      missing teeth in partially and fully edentulous cases. This article describes how
      Nobel Biocare's Procera surgical planning software converts a patient's double CT
      scan data into a virtual three-dimensional model of the alveolar bone and
      overlying prosthesis. Using these images, the practitioner virtually places
      implants in the bone in precise relation to their position in the final
      prosthesis. Procera uses this virtual plan to fabricate a customized surgical
      template that guides the placement of the implants safely, precisely, and
      accurately. Then the dental laboratory can construct the master cast and
      provisional restoration before surgery, allowing the restoration to be inserted
      immediately after placement of the implants. Furthermore, computer-based guided
      implant surgery is minimally invasive and requires a shorter chair time and fewer
      appointments than traditional methods.

PMID- 18805229
TI  - Computer-aided design/computer-aided manufacturing applications using CT and cone
      beam CT scanning technology.
AB  - CT and cone-beam CT technology provides clinicians with new methods to view
      patient anatomy exceeding conventional two-dimensional radiology. Interactive
      software applications allow for improved interpretation of the CT scan data.
      Proper use of this new technology must be based on a solid foundation of
      fundamental surgical and prosthodontic protocols. Advances in software and
      associated hardware have empowered clinicians with the necessary tools to harness
      the technology, while remaining true to conventional standards. The enhanced
      capability of innovative software applications that allow clinicians to interpret
      and maneuver through various three-dimensional images has far-reaching
      implications when interactive treatment planning software is combined with
      computer-aided design and manufacturing. Using all available virtual tools, true
      restoratively driven implant dentistry can be accomplished, ultimately benefiting
      patients.

PMID- 18805230
TI  - Cone-beam CT: applications in orthodontics.
AB  - Radiographic images have always been an important part of orthodontic diagnosis
      and treatment planning. We have been limited by the two-dimensional nature of
      these radiographs as we pursue tooth movement in a three-dimensional fashion.
      This article shows the current and future uses and advantages of cone-beam CT in
      the practice of orthodontics. The use of this technology in the near future will
      change the way records are taken and treatment is rendered. With this added
      diagnostic knowledge, orthodontic treatment will assuredly become not only more
      high tech but also higher quality.

PMID- 18805231
TI  - Cone-beam CT diagnostic applications: caries, periodontal bone assessment, and
      endodontic applications.
AB  - Cone-beam CT (CBCT) is useful for many maxillofacial applications, such as
      implant site imaging and diagnosis and treatment planning for orthodontics and
      craniofacial surgery. Dentoalveolar applications, such as carious lesion
      detection and characterization, assessment of the three-dimensional nature of
      periodontal bone topography, and various endodontic applications are less known
      and not as thoroughly studied. This article explores and assesses in vivo and in
      vitro efforts to apply CBCT imaging to these more common dentoalveolar tasks.
      CBCT imaging, like its medical counterpart, can be seen as a highly useful and,
      in some instances, indispensable part of the dental imaging armamentarium.

PMID- 18805232
TI  - Oral and maxillofacial pathology in three dimensions.
AB  - It is clear that the dental profession has entered a new age of radiographic
      diagnostic imaging. A number of examples have shown that being able to visualize
      oral and maxillofacial pathologic entities in three dimensions assists in
      diagnosing and planning the appropriate treatment. The technology is an
      improvement for our profession and for the patients it serves.

PMID- 18805233
TI  - Contemporary imaging of the temporomandibular joint.
AB  - This article discusses imaging techniques for visualization of the
      temporomandibular joint. Conventional plain film modalities are discussed
      briefly, with an emphasis on the more contemporary modalities, such as CT with
      cone-beam technology, MRI, and nuclear imaging, including single-photon emission
      computed tomography, and positron emission tomography. Indications, advantages,
      and limitations are discussed. As advancements in this area continue, our
      understanding of this complex joint and its pathology will follow, which will
      lead to more defined imaging indications and ultimately, to improved treatment
      outcomes.

PMID- 18805234
TI  - Diagnostic imaging and sleep medicine.
AB  - Obstructive sleep apnea syndrome (OSAS) is a relatively common disorder
      characterized by recurrent episodes of upper airway collapse and obstruction
      during sleep. It results in apneic events (or in the case of partial obstruction,
      hypopneic events) that lead to loud snoring, hypoxia, and arousals that interrupt
      the normal sleep cycle. Typically, these nocturnal arousals cause patients to
      complain of excessive daytime sleepiness, which may interfere with routine daily
      activities. More importantly, when moderate to severe, OSAS can lead to a wide
      variety of medical complications, some of which can result in severe consequences
      or even death.

PMID- 18805235
TI  - The future of dental and maxillofacial imaging.
AB  - Improvements in software removal of scatter artifacts; reduced x-ray dose; and
      delivery of interpretive reports, analyses, appliances, and images will continue,
      and use of cone beam volumetric tomography will increase. Distributive networks
      will be introduced to simplify all of these tasks. Virtual articulators, computer
      assisted design and computer assisted manufacturing devices will improve, and
      online delivery of some of these services will increase concomitantly.
      Consequently, dentistry will improve and, along with it, patient care.

PMID- 18805236
TI  - Gastrointestinal endoscopy. Preface.

PMID- 18805237
TI  - The pathogenesis of colorectal cancer. Foreword.

PMID- 18805238
TI  - Nonpolypoid neoplastic lesions of the colorectal mucosa.

PMID- 18805239
TI  - Medically unexplained presentations and quality of life: a study of a
      predominantly South Asian primary care population in England.
AB  - Primary care subjects from a predominantly South Asian inner-city setting in
      Manchester, UK, were studied. We aimed to determine whether medically unexplained
      symptoms (MUS) are associated with worse health-related quality of life than
      medically explained symptoms (MES), after controlling for differences in
      sociodemographic variables, number of somatic symptoms, and levels of anxiety and
      depression. One hundred nineteen subjects attending general practice completed
      questionnaires to assess somatic symptoms, anxiety, depression, and quality of
      life. Doctors' records were later studied to ascertain whether the presentation
      was medically explained. Thirty-nine subjects (33%) had medically unexplained
      presentations. Compared to patients with MES, those with MUS had significantly
      more somatic symptoms (6.9 vs. 4.3, P<.001), higher levels of anxiety (Hospital
      anxiety and depression scale -- anxiety score) (9.8 vs. 6.7, P=.004), depression
      (Hospital anxiety and depression scale -- depression) (6.8 vs. 4.5, P=.005), and
      poorer health-related quality of life (EuroQol standardized score 54.6 vs. 73.3,
      P=.001). On multiple regression analysis, anxiety, depression, and somatic
      symptom scores independently (P<.01) predicted quality of life, after controlling
      for demographic factors. Whether the presentation was medically unexplained or
      not did not contribute to the regression model (P=.85). Our findings suggest that
      it is the number of somatic symptoms and the associated anxiety/depression that
      account for greater impairment in people's health-related quality of life, and
      not whether they have a medical explanation for their symptoms.

PMID- 18805240
TI  - The base rate of effort test failure in patients with medically unexplained
      symptoms.
AB  - BACKGROUND: "Effort tests" (i.e., tests that indicate whether appropriate effort
      is being made) are increasingly used in neuropsychological assessments. However,
      not all failures on effort tests are necessarily attributable to lack of effort.
      Understanding the factors that contribute to failure on effort tests has
      important clinical implications. OBJECTIVES: This study aimed (a) to establish
      the extent to which patients with medically unexplained symptoms (MUS) presenting
      to neurology fail effort tests, (b) examine the performance of "mild" and
      "strong" simulators on effort tests, and (c) compare the performance of
      simulators and MUS patients. METHODS: Forty-three MUS patients, 35 mild
      simulators, and 39 strong simulators undertook a battery of effort tests. The
      groups were matched for age, estimated IQ, and gender. The MUS patients were not
      involved in litigation. RESULTS: The failure rate (defined as failing two or more
      effort tests) was 11% in the MUS group, 94% in the mild simulation groups, and
      100% in the strong simulation group. CONCLUSIONS: A minority of nonlitigant MUS
      patients who present to neurology fail effort tests. Possible reasons for this
      are discussed. In that they do not produce below-chance performance (in contrast
      with many of the simulators), there is no clear indication of deliberate failure,
      though this cannot be ruled out. The very high failure rate in the mild
      simulation group (who were instructed not to overact) indicates the sensitivity
      of effort tests to lack of effort and the value of including such tests in
      neuropsychological assessments.

PMID- 18805241
TI  - Effort testing in patients with neurological symptoms unexplained by disease.

PMID- 18805242
TI  - Long-term outcomes of short-term and long-term psychosomatic inpatient treatment
      and their predictors.
AB  - OBJECTIVES: The Clinic for Psychosomatic Medicine and Psychotherapy at the
      University Giessen, Germany, offers short-term (STT) and long-term inpatient
      therapy (LTT). METHODS: In a prospective, 3-year follow-up study, we examined
      therapeutic indication, short- and long-term results, outcome predictors, and the
      utilization of aftercare for both settings. RESULTS: STT patients were more
      frequently acutely ill, suffered from stronger symptomatic manifestations, and
      were more frequently employed. LTT patients had a greater rate of chronic
      psychosomatic disorders, personality disorders and somatic comorbidity. In both
      settings, distress strongly declined during inpatient therapy and remained stable
      for 3 years. Negative predictors of outcome were infantile object relation
      patterns and interpersonal problems. We found no differences between STT and LTT
      patients in terms of the utilization of aftercare. CONCLUSION: Duration of
      psychosomatic inpatient treatment should be differentiated according to the
      chronicity and nature of the disorder.

PMID- 18805243
TI  - Somatic and psychological dimensions of screening for psychiatric morbidity: a
      community validation of the SPHERE Questionnaire.
AB  - OBJECTIVE: Nonspecific somatic symptoms play an important role in the
      manifestation of psychiatric morbidity. This study examined the psychometric
      performance of an instrument developed to improve the rates of identification of
      psychiatric disorders, which incorporated somatic and psychological dimensions of
      distress (the Somatic and Psychological Health Report, or SPHERE). METHODS: Eight
      hundred twenty-one adults who were participating in an epidemiological
      longitudinal study of the psychological impact of childhood disaster exposure
      (mean age of 28.23 years, S.D. of 2.29, range of 22-34) were recruited out of the
      original cohort of 1531. The 34-item SPHERE was administered in a self-report
      booklet, and the subjects were interviewed using the Composite International
      Diagnostic Interview to ascertain current and lifetime psychiatric diagnoses.
      RESULTS: While the negative predictive power was high (96.1% for current disorder
      and 81.7% for lifetime disorder), the positive predictive power was low (56.8%
      for a lifetime disorder and 27.5% for current disorder). This was despite 61.6%
      of lifetime sufferers and 78.6% who met current criteria for any disorder
      screened positive using the SPHERE. Sensitivity was highest when the broad "PSYCH
      or SOMA" screen was used (78.6%). Specificity of 89.5% was obtained for the
      "PSYCH and SOMA" scale. CONCLUSIONS: In this population of young adults, where
      age limited the prevalence of comorbid physical disease, the SPHERE was an
      acceptable screening measure. The psychometric performance was better for
      lifetime than current disorder. The psychometric characteristics of this
      instrument indicate that its particular use may be in defining individuals who
      need a more detailed assessment in a clinical setting.

PMID- 18805244
TI  - Somatic and psychiatric comorbidity in the general elderly population: results
      from the ZARADEMP Project.
AB  - OBJECTIVE: In a representative sample of the elderly population in a southern
      European city, we tested the hypothesis that there is an association between
      general somatic and general psychiatric morbidity. METHODS: A stratified random
      sample of 4803 individuals aged > or =55 years was selected for the baseline
      study in the ZARADEMP Project. The elderly were assessed with standardized
      Spanish versions of instruments, including the Geriatric Mental State (GMS)
      AGECAT. Psychiatric cases were diagnosed according to GMS-AGECAT criteria, and
      somatic morbidity was documented with the EURODEM Risk Factors Questionnaire.
      RESULTS: General comorbidity clustered in 19.9% of the elderly when hypertension
      was removed from the somatic conditions category, with 33.5% of the sample
      remaining free from both somatic and psychiatric illnesses. General comorbidity
      was associated with age, female gender, and limited education, but did not
      increase systematically with age. The frequency of psychiatric illness was higher
      among the somatic cases than among noncases, and the frequency of somatic
      morbidity among the psychiatric cases was higher than among noncases. This
      association between somatic and psychiatric morbidity remained statistically
      significant after controlling for age, gender, and education [odds ratio
      (OR)=1.61; confidence interval (CI)=1.38-1.88]. Most somatic categories were
      associated with psychiatric illness, but after adjusting for demographic
      variables and individual somatic illnesses, the association remained
      statistically significant only for cerebrovascular accidents (CVAs) (OR=1.47;
      CI=1.09-1.98) and thyroid disease (OR=1.67; CI=1.10-2.54). CONCLUSION: This is
      the first study to document that there is a positive and statistically
      significant association between general somatic morbidity and general psychiatric
      morbidity in the (predominantly) elderly population. CVAs and thyroid disease may
      have more weight in this association.

PMID- 18805245
TI  - Identifying teachers at risk in Hong Kong: Psychosomatic symptoms and sources of
      stress.
AB  - OBJECTIVE: The present study attempts to examine the relationships between
      certain common psychosomatic symptoms and sources of stress in Hong Kong
      teachers. METHODS: A total of 261 teachers (134 males and 127 females) from 13
      high schools in different regions of Hong Kong responded to the Teacher Stress
      Inventory (TSI) with a return rate of 52.2%. Retired and in-service teachers were
      involved in the development of TSI, which included items related to sources of
      stress in the context of Hong Kong education system, psychosomatic symptoms in
      the form of stress arousal, and global stress. RESULTS: Confirmatory factor
      analysis identified six distinct teacher stress sources: students, others,
      curriculum, nonteaching duties, teaching workload, and recognition. These stress
      sources were positively correlated with a global teacher stress measure,
      supporting their construct validity. Structural equation models showed that each
      stress source was positively related to teachers' psychosomatic symptoms, to
      which the path coefficient from teaching workload was the highest (beta=.47,
      P<.05). CONCLUSION: The heavy workload experienced by the Hong Kong teachers that
      is directly related to the daily teaching routine tends to be the most
      detrimental to their health conditions. Measures such as reducing teacher-student
      ratio by adopting smaller class sizes, increasing teacher numbers, and reframing
      teaching practice should be given due consideration in Hong Kong. There is a need
      for the inclusion of stress management programs for both trainees and in-service
      teachers.

PMID- 18805246
TI  - "Don't crack under pressure!"--Do leisure time physical activity and self-esteem
      moderate the relationship between school-based stress and psychosomatic
      complaints?
AB  - OBJECTIVE: Stressful experiences occupy a central role in most etiological models
      of developmental psychopathology. Stress alone, however, insufficiently explains
      negative health outcomes. This raises the question why some children and
      adolescents are more vulnerable to the development of psychopathological symptoms
      than others. The primary purpose of this research was to demonstrate whether
      leisure time physical activity and self-esteem protect against stress-induced
      health problems. METHOD: The findings are based on a cross-sectional study of 407
      Swiss boys and girls (M=14.01 years). All variables are self-reported. Analyses
      of covariance were applied to test for main and moderator effects. RESULTS: The
      findings suggest that school-based stress and psychosomatic complaints are
      important issues during adolescence. The results show that a higher level of
      psychosomatic complaints accompanies stress. Surprisingly, psychosomatic
      complaints and physical activity were unrelated. Likewise, no association was
      found between physical activity and stress. In contrast, students with high self
      esteem reported significantly less complaints and a lower extent of perceived
      stress. Finally, the results do not support the stress-moderation hypothesis.
      Neither physical activity nor self-esteem buffered against the detrimental
      effects of school-based stress on psychosomatic health. CONCLUSION: The findings
      lend support to previous research with German-speaking samples but are in marked
      contrast to Anglo-Saxon studies, which generally support the role of physical
      activity as a moderator of the health-illness relationship. In this
      investigation, developmental features and methodological limitations may have
      accounted for the insignificant results.

PMID- 18805247
TI  - The background biopsychosocial status of teachers with voice problems.
AB  - OBJECTIVE: The aim of the study was to explore the background biopsychosocial
      status of teachers with a relative voice handicap. The study also intended to
      investigate this biopsychosocial status in relation to behavior of not always
      reporting voice complaints. METHODS: This research was a cross-sectional survey,
      performed using questionnaires: a general voice questionnaire, the Voice Handicap
      Index (VHI), and the Symptom Checklist-90 (SCL-90). The focus of the study is on
      those teachers who score the highest and the lowest on the SCL-90 as they report
      a higher or lower level of overall physical and psychosocial dysfunction. Fifty
      five teachers score in the lowest quartile and 51 teachers score in the highest
      quartile of the total score of the SCL-90 (N=106 teachers). The upper quartiles
      of SCL-90 scores are mentioned as "high scores" and the lower quartile scores are
      mentioned as "low scores". VHI scores above the 75th percentile are referred to
      as "high voice handicap" and VHI scores below the 25th percentile are referred to
      as "low voice handicap". RESULTS: Subjects who had a high voice handicap have a
      greater relative risk for a high score on all the subscales (ORs between 2.1 and
      20.2) and total score (OR=12.5) of the SCL-90. Teachers who had a high voice
      handicap and who did not report voice complaints have a greater relative risk for
      a high score for all the subscales (ORs between 1.8 and 24.5) and total score
      (OR=22.4) of the SCL-90. CONCLUSION: The voice handicap and the behaviour of
      nonreporting of voice complaints when having a voice handicap appear to be in
      relation to the biopsychosocial status of the teachers.

PMID- 18805248
TI  - Stressor, perceived stress and recurrent pain in Swedish schoolchildren.
AB  - OBJECTIVE: Stress is an important etiological factor for pain. Little is known,
      however, about how this process is mediated. The aim of this study is to
      highlight how more stress corresponds with the amount of reported perceived
      stress, pain symptom, and the co-occurrence of two pain symptoms--headache and
      abdominal pain--and how these three phenomena are related. We have also studied
      possible gender differences. METHODS: A cross-sectional study based on data from
      child supplements linked to national household surveys in Sweden during 2002
      2003. Information concerning harassment, perceived stress, headache, and
      abdominal pain was gathered from a questionnaire. The study population consisted
      of a representative national sample of 2597 children aged 10-18 years. RESULTS:
      Children's reports of exposure to the stressor harassment were associated with
      their subjective perception of stress and recurrent pain in a stepwise manner.
      Having both pain symptoms was more strongly associated with the stressor
      harassment and perceived stress than having only one pain symptom. This was
      especially true of girls, who reported higher levels of stress symptoms and who
      had a different profile of pain symptoms than boys. CONCLUSIONS: The stressor
      harassment, perceived stress, and recurrent pain are associated with each other
      in a stepwise fashion. The co-occurrence of headache and abdominal pain is much
      more closely associated with harassment and perceived stress than any of these
      symptoms separately, especially in girls.

PMID- 18805249
TI  - Stress management effects on perceived stress and cervical neoplasia in low
      income HIV-infected women.
AB  - OBJECTIVE: Risk for developing cervical neoplastic disease is greatly increased
      in women infected with oncogenic sexually transmitted human papillomaviruses
      (HPVs) and who have lowered cellular immunity due to coinfection with human
      immunodeficiency virus (HIV) infection. The majority of these individuals are low
      income minority women. Factors associated with promotion of HPV to cervical
      neoplasia in HIV-infected populations include degree of immunosuppression as well
      as behavioral factors such as tobacco smoking and psychological stress. This
      study examined the effects of a cognitive behavioral stress management (CBSM)
      intervention on life stress and cervical neoplasia in HIV+ minority women.
      METHODS: Participants were 39 HIV+ African-American, Caribbean, and Hispanic
      women with a recent history of an abnormal Papanicolaou smear. Participants
      underwent colposcopic examination, psychosocial interview, and peripheral venous
      blood draw at study entry and 9 months after being randomly assigned to either a
      10-week CBSM group intervention (n=21) or a 1-day CBSM workshop (n=18). RESULTS:
      Women assigned to the 10-week group-based CBSM intervention reported decreased
      perceived life stress and had significantly lower odds of cervical neoplasia over
      a 9-month follow-up. CBSM effects on life stress and neoplasia appeared
      independent of presence of neoplasia at study entry, HPV type, CD4+CD3+ cell
      count, HIV viral load, and substance use. Furthermore, CBSM intervention effects
      on cervical neoplasia were especially pronounced among women with residual life
      stress at follow-up. CONCLUSION: These findings suggest that stress management
      decreases perceived life stress and may decrease the odds of cervical neoplasia
      in women with HIV and a history of abnormal Papanicolaou smears. Although
      preliminary, these findings suggest the utility of stress management as a cancer
      prevention strategy in this high-risk population.

PMID- 18805250
TI  - Seeking a higher standard for degenerative mitral valve repair: begin with
      etiology.

PMID- 18805251
TI  - The effect of pure mitral regurgitation on mitral annular geometry and three
      dimensional saddle shape.
AB  - OBJECTIVE: Chronic ischemic mitral regurgitation is associated with mitral
      annular dilatation in the septal-lateral dimension and flattening of the annular
      3-dimensional saddle shape. To examine whether these perturbations are caused by
      the ischemic insult, mitral regurgitation, or both, we investigated the effects
      of pure mitral regurgitation (low pressure volume overload) on annular geometry
      and shape. METHODS: Eight radiopaque markers were sutured evenly around the
      mitral annulus in sheep randomized to control (CTRL, n = 8) or experimental
      (HOLE, n = 12) groups. In HOLE, a 3.5- to 4.8-mm hole was punched in the
      posterior leaflet to generate pure mitral regurgitation. Four-dimensional marker
      coordinates were obtained radiographically 1 and 12 weeks postoperatively. Mitral
      annular area, annular septal-lateral and commissure-commissure dimensions, and
      annular height were calculated every 16.7 ms. RESULTS: Mitral regurgitation grade
      was 0.4 +/- 0.4 in CTRL and 3.0 +/- 0.8 in HOLE (P < .001) at 12 weeks. End
      diastolic left ventricular volume index was greater in HOLE at both 1 and 12
      weeks; end-systolic volume index was larger in HOLE at 12 weeks. Mitral annular
      area increased in HOLE predominantly in the commissure-commissure dimension, with
      no difference in annular height between HOLE versus CTRL at 1 or 12 weeks,
      respectively. CONCLUSION: In contrast with annular septal-lateral dilatation and
      flattening of the annular saddle shape observed with chronic ischemic mitral
      regurgitation, pure mitral regurgitation was associated with commissure
      commissure dimension annular dilatation and no change in annular shape. Thus,
      infarction is a more important determinant of septal-lateral dilatation and
      annular shape than mitral regurgitation, which reinforces the need for disease
      specific designs of annuloplasty rings.

PMID- 18805253
TI  - Is the European System for Cardiac Operative Risk Evaluation model valid for
      estimating the operative risk of patients considered for percutaneous aortic
      valve replacement?
AB  - OBJECTIVE: The European System for Cardiac Operative Risk Evaluation has been
      used to define a particularly high-risk group of patients for aortic valve
      replacement in whom alternative procedures, such as stent-mounted percutaneous
      valve procedures, may be appropriate. Our objective was to assess the validity of
      this risk assessment at a large-volume, tertiary cardiac surgical center.
      METHODS: From January 1, 2000, to December 30, 2006, a total of 1177 patients
      underwent isolated aortic valve replacement at the Mayo Clinic. Patient and
      operative demographics were recorded in a prospective database. Early mortality
      (< or = 30 days) was obtained. Additive and logistic European System for Cardiac
      Operative Risk Evaluations were calculated for each patient. RESULTS: The mean
      patient age was 68.0 years (+/-14.7 years) at the time of surgery, and 36.8% were
      female. Variables used in the calculation of the European System for Cardiac
      Operative Risk Evaluation included chronic lung disease (15% of our cohort),
      extracardiac arteriopathy (13.8%), neurologic dysfunction (0.2%), previous
      cardiac surgery (23.2%), renal failure (6.5%), active endocarditis (3.1%), recent
      myocardial infarction (1.1%), unstable angina (0.1%), and severe pulmonary
      hypertension (6.5%). The ejection fraction was severely reduced (< or = 30%) in
      4.9% of patients and moderately reduced (< or = 50%) in 12.7% of patients. One
      percent of patients were in a critical state, and operation was performed
      urgently in 3.4% of patients. Although mean mortality estimates were 6.9% +/-
      3.4% (additive European System for Cardiac Operative Risk Evaluation) and 10.9%
      +/- 12.7% (logistic European System for Cardiac Operative Risk Evaluation),
      actual overall operative mortality in our patients was 2.5%. Additive and
      logistic European System for Cardiac Operative Risk Evaluations overestimated
      operative mortality in low, intermediate, and high-risk subgroups by up to 17.8%.
      CONCLUSIONS: The European System for Cardiac Operative Risk Evaluation should not
      be used to determine the operability of patients for isolated aortic valve
      replacement. Elevated European System for Cardiac Operative Risk Evaluations
      alone do not appropriately define a population for use of a percutaneous aortic
      valve.

PMID- 18805254
TI  - Extracorporeal circulation by peripheral cannulation before redo sternotomy:
      indications and results.
AB  - OBJECTIVES: Cardiac reoperations are challenging and time-consuming, and have a
      high risk for reentry injuries. We discuss the indications, advantages, and
      technologic features of cardiopulmonary bypass by peripheral cannulation before
      resternotomy. METHODS: Of 610 redo cardiac interventions from 2000 to 2006, 158
      (25.9%) were performed with peripheral cannulation and ongoing cardiopulmonary
      bypass before resternotomy. This was indicated in the following: close adhesions
      between the sternum and the anterior cardiac surface; ascending aorta or bypass
      grafts (computed tomography scan); and patients with functional tricuspid
      regurgitation, hemodynamic/electric instability, previous mediastinitis, or
      depressed ejection fraction. Intraoperative transesophageal echocardiography was
      always performed. RESULTS: Venous drainage was obtained by cannulation of the
      common femoral vein (Seldinger technique) and right internal jugular vein
      (percutaneously). Arterial nonocclusive cannula was placed in the femoral artery
      (Seldinger technique). Cardiopulmonary bypass time before cardiotomy was 35 +/-
      14.7 minutes. There were 5 perioperative deaths, none due to reentry injury.
      Damage to mediastinal structures at resternotomy occurred in 4 cases. In all
      cases, peripheral cardiopulmonary bypass allowed adequate and comfortable repair.
      The operative time was 296 +/- 60 minutes. The average total postoperative
      bleeding was 264 +/- 38 mL/m(2). No patient experienced complications related to
      femoral cannulation. The Seldinger method allowed little vascular trauma and
      intraoperative patency of femoral vessels. CONCLUSION: In selected patients,
      cardiopulmonary bypass before resternotomy is a valid and reproducible option to
      render cardiac reoperations safer and more expeditious in the reentry phase. The
      absence of cannulae in the operating field makes the procedure more comfortable.
      The liberal use of this strategy is recommended in redo cases.

PMID- 18805255
TI  - Structure and function relationships of the helical ventricular myocardial band.
AB  - OBJECTIVE: Understanding cardiac function requires knowledge of the architecture
      responsible for the normal actions of emptying and filling. Newer imaging methods
      are surveyed to characterize directional (narrowing, shortening, lengthening, and
      widening) and twisting motions. METHODS: These movements are defined and then
      compared with a spectrum of models to introduce a useful "functional anatomy"
      that explains cardiac spatial and temporal relationships. The sequential nature
      of normal contraction differs from a synchronous beat. RESULTS: The prior concept
      of constriction is replaced by understanding that clockwise and counterclockwise
      helical motions are necessary to cause the predominant twisting motion. The
      helical ventricular myocardial band model of Torrent-Guasp fulfills the
      architectural structure to define normal function. Expansion of information from
      this model allows novel understanding of mechanisms that explains why a component
      of ventricular suction involves a systolic event, clarifies septum function,
      determines diastolic dysfunction, introduces new treatments, shows how knowledge
      of the helical structure influences understanding of atrioventricular and
      biventricular pacing, and creates novel methods for introducing septal pacing
      stimuli. CONCLUSION: Further testing of these spatial anatomic concepts is needed
      to create a more accurate understanding of the architectural mechanisms that
      underlie cardiac dynamics to address future problems in unhealthy hearts.

PMID- 18805256
TI  - Mitral valve motion after performing an edge-to-edge repair in an isolated swine
      heart.
AB  - OBJECTIVES: Mitral valve motion after performing an edge-to-edge repair is a
      major concern, but it has not yet been observed directly. Mitral valve motion was
      assessed by using a high-speed digital video camera and microsonometric analysis
      in an isolated swine heart, and any changes in the mitral valve area or the
      development of mitral stenosis symptoms were evaluated. METHODS: A temporary edge
      to-edge repair model was created. The mitral valve motion was assessed by using a
      high-speed digital video camera, and the motion of the mitral annulus was
      measured by means of sonomicrometric analysis with or without performing edge-to
      edge repair (n = 5). The left ventricular volumetric measurements were also
      measured with a conductance catheter. One cardiac cycle was divided into 4
      phases: the mitral valve open phase, the isovolumic contraction phase, the aortic
      valve open phase, and the isovolumic relaxation phase. RESULTS: The mitral valve
      was divided into 2 orifices by using the edge-to-edge technique, and the mitral
      valve area decreased by approximately 30%. The ratio of mitral valve open phase
      significantly decreased (31.9% +/- 3.4% vs 41.4% +/- 3.7%, P = .04). There were
      no significant differences in the diameter and the changes of anteroposterior
      dimensions of the mitral annulus. The stroke volume and the peak positive and
      negative dp/dt values showed no obvious change, but dv/dt values increased
      slightly without significance after removing the edge-to-edge suture (118 +/- 25
      vs 130 +/- 17 mL/s, P = .14). CONCLUSIONS: The mitral valve area decreased
      slightly; however, edge-to-edge repair did not create symptomatic mitral stenosis
      and showed no adverse affects on cardiac function.

PMID- 18805257
TI  - Quality of life outcomes are equivalent after lobectomy in the elderly.
AB  - OBJECTIVE: Prospective analyses of quality of life in elderly patients after
      lobectomy are limited, yet surgeons often recommend suboptimal therapy to these
      patients on the basis of the belief that lobectomy is poorly tolerated. Surgical
      decision making in elderly patients with lung cancer is better informed when the
      benefits to survival and quality of life after lobectomy are understood. METHODS:
      By using a validated quality of life instrument, 422 patients were prospectively
      assessed preoperatively and 3, 6, and 12 months after lobectomy. Outcomes were
      analyzed with respect to age (group 1: < 70 years and group 2: > or = 70 years).
      The outcome domains of physical functioning, role functioning, emotional
      functioning, cognitive functioning, social functioning, global health, and pain
      in the chest were analyzed using a mixed model. The trend in quality of life was
      determined according to age. The Kaplan-Meier method was used for analysis of
      overall survival. RESULTS: The mean age was 60.1 years in group 1 (N = 256) and
      74.7 years in group 2 (N = 166). Baseline demographics and quality of life were
      similar except that group 2 had better emotional functioning scores and worse
      pain in the chest scores. Postoperatively, both groups demonstrated significant
      decreases in quality of life at 3 months. However, at 6 and 12 months, all
      domains had returned to baseline except physical functioning, which remained
      below baseline in group 2. Emotional functioning improved postoperatively for
      both groups. Overall survival at 5 years was not different between groups.
      CONCLUSION: By using a validated quality of life assessment tool with
      measurements at baseline and serially after resection in a large patient
      population, this analysis quantifies the degree of impairment of quality of life
      after lobectomy and documents time to full recovery for both age groups.

PMID- 18805259
TI  - The impact of lymph node station on survival in 348 patients with surgically
      resected malignant pleural mesothelioma: implications for revision of the
      American Joint Committee on Cancer staging system.
AB  - OBJECTIVES: The propensity of malignant pleural mesothelioma to metastasize to N1
      or N2 nodes and their corresponding prognostic value is unclear. The American
      Joint Committee on Cancer staging system groups N1 and N2 disease together as
      stage III. The goal of this study was to define the prognostic value of specific
      nodal stations. METHODS: Patients with malignant pleural mesothelioma who
      underwent resection were identified from an institutional database. Nodal
      stations were defined by the American Joint Committee on Cancer lung cancer node
      map classification. Survival was analyzed by the Kaplan-Meier method, log-rank
      test, and Cox proportional hazards analysis. RESULTS: From 1990 to 2006, 348
      patients were identified: 279 men and 69 women with a median age of 67 years
      (range 26-85 years). Extrapleural pneumonectomy was performed in 223 cases, and
      pleurectomy/decortication was performed in 125 cases. Survival differences (P <
      .01) were observed between 2 groups: N0 or N1(+) (median survival = 19 months)
      and N2(+), N2/N1(+) and internal thoracic(+) (median survival = 10 months).
      Survival was influenced by the number of involved N2 stations (0, 1, 2, or more:
      P < .001). Multivariate analysis grouping all N2 and internal thoracic(+) versus
      N1(+) and N0 demonstrated a hazard ratio for survival of 1.7 (P < .0001)
      controlling for T3/T4 status (hazard ratio = 1.3, P < .01), non-epithelioid
      histology (hazard ratio = 1.7, P < .0001), extrapleural pneumonectomy (1.1, P =
      .4), and male gender (hazard ratio 1.4, P < .01). CONCLUSION: This study confirms
      a preferential pattern of drainage of malignant pleural mesothelioma to N2 rather
      than N1 lymph nodes, but suggests that N1 only nodal involvement should be
      classified as lower stage disease. Multiple N2 nodal site involvement could
      potentially be classified as higher stage disease than single station N2. Our
      results emphasize the need for larger, confirmatory multicenter studies that
      could lead to revision of the current staging system.

PMID- 18805261
TI  - Difficulties encountered managing nodules detected during a computed tomography
      lung cancer screening program.
AB  - OBJECTIVE: The main challenge of screening a healthy population with low-dose
      computed tomography is to balance the excessive use of diagnostic procedures with
      the risk of delayed cancer detection. We evaluated the pitfalls, difficulties,
      and sources of mistakes in the management of lung nodules detected in volunteers
      in the Cosmos single-center screening trial. METHODS: A total of 5201
      asymptomatic high-risk volunteers underwent screening with multidetector low-dose
      computed tomography. Nodules detected at baseline or new nodules at annual
      screening received repeat low-dose computed tomography at 1 year if less than 5
      mm, repeat low-dose computed tomography 3 to 6 months later if between 5 and 8
      mm, and fluorodeoxyglucose positron emission tomography if more than 8 mm.
      Growing nodules at the annual screening received low-dose computed tomography at
      6 months and computed tomography-positron emission tomography or surgical biopsy
      according to doubling time, type, and size. RESULTS: During the first year of
      screening, 106 patients underwent lung biopsy and 91 lung cancers were identified
      (70% were stage I). Diagnosis was delayed (false-negative) in 6 patients (stage
      IIB in 1 patient, stage IIIA in 3 patients, and stage IV in 2 patients),
      including 2 small cell cancers and 1 central lesion. Surgical biopsy revealed
      benign disease (false-positives) in 15 cases (14%). Positron emission tomography
      sensitivity was 88% for prevalent cancers and 70% for cancers diagnosed after
      first annual screening. No needle biopsy procedures were performed in this cohort
      of patients. CONCLUSION: Low-dose computed tomography screening is effective for
      the early detection of lung cancers, but nodule management remains a challenge.
      Computed tomography-positron emission tomography is useful at baseline, but its
      sensitivity decreases significantly the subsequent year. Multidisciplinary
      management and experience are crucial for minimizing misdiagnoses.

PMID- 18805262
TI  - Pectoralis major-rectus abdominis bipedicled muscle flap in the treatment of
      poststernotomy mediastinitis.
AB  - OBJECTIVES: Although the incidence of infected sternotomy wounds after median
      sternotomy for cardiovascular surgery is relatively low (0.5% to 5%), it is
      associated with significant morbidity and a long period of treatment. Today,
      muscle flaps, such as the pectoralis major or the rectus abdominis, are widely
      accepted as a mainstay of reconstructive options. Each method carries unavoidable
      limitations and setbacks of its own. To overcome the disadvantages of the
      pectoralis muscle and rectus abdominis muscle flaps, we designed and performed a
      pectoralis major-rectus abdominis muscle bipedicled flap for the coverage of
      sternal defects. METHODS: The pectoralis major-rectus abdominis bipedicled flap
      was elevated as a single unit, preserving the thoracoepigastric fascia in
      continuity with the rectus muscle and its anterior fascia. The method was used in
      27 patients with postoperative mediastinitis during a 5-year period. RESULTS: The
      bipedicled flap could fill the defect with sufficient volume, not only in the
      upper two thirds but also in the lower one third of the sternum. Recurrent
      uncontrolled infection developed in 11% of all cases, and upper abdominal fascial
      attenuation was observed in 1 patient. There were no surgical intervention
      related complications or deaths. CONCLUSIONS: We conclude that pectoralis major
      rectus abdominis bipedicled flap is a practical and efficacious method in the
      reconstruction of the anterior chest wall defect caused by poststernotomy
      mediastinitis. It not only provides sufficient volume to fill the entire
      mediastinum but also affords resolution of the infected wound with favorable
      outcomes comparable with those of other methods.

PMID- 18805263
TI  - Ross operation: 16-year experience.
AB  - OBJECTIVE: We performed a review of a consecutive series of 487 patients
      undergoing the Ross operation to identify surgical techniques and clinical
      parameters that affect outcome. METHODS: We performed a prospective review of
      consecutive patients from August 1986 through June 2002 and follow-up through
      August 2004. Patient age was 2 days to 62 years (median, 24 years), and 197
      patients were less than 18 years of age. The Ross operation was performed as a
      scalloped subcoronary implant in 26 patients, an inclusion cylinder in 54
      patients, root replacement in 392 patients, and root-Konno procedure in 15
      patients. Clinical follow-up in 96% and echocardiographic evaluation in 77% were
      performed within 2 years of closure. RESULTS: Actuarial survival was 82% +/- 6%
      at 16 years, and hospital mortality was 3.9%. Freedom from autograft failure
      (autograft reoperation and valve-related death) was 74% +/- 5%. Male sex and
      primary diagnosis of aortic insufficiency (no prior aortic stenosis) were
      significantly associated with autograft failure by means of multivariate
      analysis. Freedom from autograft valve replacement was 80% +/- 5%. Freedom from
      endocarditis was 95% +/- 2%. One late thromboembolic episode occurred. Freedom
      from allograft reoperation or reintervention was 82% +/- 4%. Freedom from all
      valve-related events was 63% +/- 6%. In children survival was 84% +/- 8%, and
      freedom from autograft valve failure was 83% +/- 6%. CONCLUSIONS: The Ross
      operation provides excellent survival in adults and children willing to accept a
      risk of reoperation. Male sex and a primary diagnosis of aortic insufficiency had
      a negative effect on late results.

PMID- 18805264
TI  - Elevated preoperative hemoglobin A1c level is predictive of adverse events after
      coronary artery bypass surgery.
AB  - OBJECTIVE: Diabetes mellitus has been associated with an increased risk of
      adverse outcomes after coronary artery bypass grafting. Hemoglobin A1c is a
      reliable measure of long-term glucose control. It is unknown whether adequacy of
      diabetic control, measured by hemoglobin A1c, is a predictor of adverse outcomes
      after coronary artery bypass grafting. METHODS: Of 3555 consecutive patients who
      underwent primary, elective coronary artery bypass grafting at a single academic
      center from April 1, 2002, to June 30, 2006, 3089 (86.9%) had preoperative
      hemoglobin A1c levels obtained and entered prospectively into a computerized
      database. All patients were treated with a perioperative intravenous insulin
      protocol. A multivariable logistic regression model was used to determine whether
      hemoglobin A1c, as a continuous variable, was associated with in-hospital
      mortality, renal failure, cerebrovascular accident, myocardial infarction, and
      deep sternal wound infection after coronary artery bypass grafting. Receiver
      operating characteristic curve analysis identified the hemoglobin A1c value that
      maximally discriminated outcome dichotomies. RESULTS: In-hospital mortality for
      all patients was 1.0% (31/3089). An elevated hemoglobin A1c level predicted in
      hospital mortality after coronary artery bypass grafting (odds ratio 1.40 per
      unit increase, P = .019). Receiver operating characteristic curve analysis
      revealed that hemoglobin A1c greater than 8.6% was associated with a 4-fold
      increase in mortality. For each unit increase in hemoglobin A1c, there was a
      significantly increased risk of myocardial infarction and deep sternal wound
      infection. By using receiver operating characteristic value thresholds, renal
      failure (threshold 6.7, odds ratio 2.1), cerebrovascular accident (threshold 7.6,
      odds ratio 2.24), and deep sternal wound infection (threshold 7.8, odds ratio
      5.29) occurred more commonly in patients with elevated hemoglobin A1c.
      CONCLUSION: Elevated hemoglobin A1c level was strongly associated with adverse
      events after coronary artery bypass grafting. Preoperative hemoglobin A1c testing
      may allow for more accurate risk stratification in patients undergoing coronary
      artery bypass grafting.

PMID- 18805266
TI  - Evolving arch surgery using integrated antegrade selective cerebral perfusion:
      impact of axillary artery perfusion.
AB  - OBJECTIVE: The study objective was to determine the impact of integrated
      antegrade selective cerebral perfusion with right axillary artery perfusion
      during arch surgery. METHODS: All surgeries were performed through a median
      sternotomy. Direct cannulation of the right axillary artery in the axilla was
      used for cardiopulmonary bypass and antegrade selective cerebral perfusion under
      hypothermia. In addition, ascending aortic or femoral artery perfusion was used.
      The clinical records of 531 patients (median age, 72 years) between 1999 and 2006
      were reviewed, of whom 137 patients (25.8%) underwent emergency surgery. There
      were 164 dissecting and 367 nondissecting aortic lesions. The surgeries included
      total arch replacement in 431 patients, partial arch replacement in 9 patients,
      and hemiarch replacement in 91 patients. RESULTS: The early mortality rate was
      4.0% (2.3% of 30-day mortality and 1.7% of in-hospital mortality). The incidence
      of permanent neurologic dysfunction was 2.9% in all (3.3% in total arch
      replacement and 1.0% in hemiarch or partial arch replacement). The incidence of
      temporary dysfunction was 9.9% in all (10.6% in total arch replacement and 7.0%
      in hemiarch or partial arch replacement). Multivariate analysis demonstrated that
      the risk factors for early mortality were chronic renal failure, ruptured
      nondissecting aneurysm, and prolonged surgery. The midterm survival was 87.2% +/-
      1.7% at 3 years and 80.5% +/- 2.6% at 5 years. CONCLUSION: Right axillary artery
      perfusion is an advantageous adjunct to cardiopulmonary bypass and antegrade
      selective cerebral perfusion in arch surgery.

PMID- 18805268
TI  - Chylopericardium in adults: a literature review over the past decade (1996-2006).
AB  - OBJECTIVES: We present a systematic overview of the literature on reported cases
      of chylous pericardial effusion in adults over the past 10 years, assessing
      clinical presentation, etiology, diagnosis, and treatment. METHODS: We conducted
      an evidence-based literature review searching for all reported adult cases of
      chylopericardium in the past 10 years (January 1996-December 2006). RESULTS: A
      total of 33 reported cases of chylopericardium were identified through a
      systematic literature search. There was no gender bias in the incidence of
      chylous pericardial effusion. Age at diagnosis varied from 18 to 68 years with a
      mean +/- standard deviation of 36.78 +/- 14.71 years. Time from symptom onset to
      diagnosis was variable (ranging from acute presentation to several years). The
      most common reported etiology was idiopathic. The diagnosis was made by
      pericardiocentesis in all patients. A search for secondary causes included
      computed tomography of the chest, lymphoscintigraphy, and lymphangiography along
      with radioactive oral (131)I-triolein. Conservative therapy was prescribed in 28
      patients and failed in 16, in whom subsequent surgery was necessary. Overall, 21
      patients underwent various types of surgery. Thoracic duct ligation with creation
      of a pericardial window was the most common surgical procedure. CONCLUSION:
      Chylopericardium is a rare entity. The fluid appearance, triglyceride content,
      cytologic characteristics, and negative cultures are crucial to make the correct
      diagnosis. Treatment is dependent on the etiology. Surgical management is the
      most successful. Conservative therapy is reserved for patients with idiopathic
      chylopericardium, those with an untreatable etiology, those considered at high
      risk for surgical treatment, or those with a predictably short lifespan.

PMID- 18805269
TI  - Early and long-term outcomes in the elderly: comparison between off-pump and on
      pump techniques in 1191 patients undergoing coronary artery bypass grafting.
AB  - OBJECTIVE: The aim of the present study was to investigate the influence of off
      pump coronary artery bypass grafting on early and long-term mortality and
      morbidity in a consecutive series of elderly patients (aged > 65 years) compared
      with conventional coronary artery bypass grafting. METHODS: From January of 1999
      to December of 2003, data were extracted for 1191 patients aged more than 65
      years: a conventional coronary artery bypass grafting group (n = 744) and an off
      pump coronary artery bypass grafting group (n = 447). Age-related early outcomes
      of interest were in-hospital mortality and postoperative morbidities. Long-term
      outcomes, including total mortality, repeated revascularization, Q-wave
      myocardial infarction, stroke, readmission, and the combination of death, Q-wave
      myocardial infarction, stroke, and repeated revascularization, were evaluated
      with Cox regression analysis. RESULTS: Univariate analysis for early outcomes
      showed significant benefits from off-pump coronary artery bypass grafting. After
      adjustment for baseline characteristics, there was still a benefit of off-pump
      coronary artery bypass grafting. Kaplan-Meier survival analyses (propensity
      matched cases) showed that stroke, major adverse cardiac and cerebrovascular
      events, and readmission occurred more frequently in the off-pump coronary artery
      bypass grafting group (P < .001). There was a nonsignificant trend to higher
      total mortality (P = .193) and higher repeated revascularization rates (P = .067)
      in the off-pump coronary artery bypass grafting group. Cox regression for long
      term outcomes showed that patients in the off-pump coronary artery bypass
      grafting group had a higher incidence of stroke (hazard ratio 2.611, 95%
      confidence interval 2.152-3.070), readmission (hazard ratio 2.000, 95% confidence
      interval 1.747-2.253), and major adverse cardiac and cerebrovascular events
      (hazard ratio 1.764, 95% confidence interval 1.456-2.072). CONCLUSION: Our
      analysis shows that off-pump coronary artery bypass grafting compared with
      conventional coronary artery bypass grafting was associated with favorable early
      outcomes in the elderly population. However, the early benefits of off-pump
      coronary artery bypass grafting were not maintained in the long term, and off
      pump coronary artery bypass grafting showed trends toward worse long-term
      results.

PMID- 18805270
TI  - Socioeconomic status and comorbidity as predictors of preoperative quality of
      life in cardiac surgery.
AB  - OBJECTIVE: Preoperative quality of life of patients undergoing cardiac surgical
      procedures has been associated with postoperative morbidity, survival, and
      quality of life. Patients of lower socioeconomic status have disproportionately
      greater cardiovascular disease burden and more complications of cardiovascular
      disease. We examined the interactive effects of demographic characteristics,
      socioeconomic status, and comorbidity on preoperative functional quality of life
      measured by the well-validated cardiovascular disease-specific Duke Activity
      Status Index. METHODS: The patient population consisted of 5581 patients between
      May 1995 and January 1999 who underwent operations on cardiopulmonary bypass:
      isolated coronary artery bypass grafting, isolated valve procedures, or combined
      coronary artery bypass grafting and valve procedures and had a preoperative Duke
      Activity Status Index, along with socioeconomic status information from United
      States 2000 census data. Predictors were identified by logistic regression for
      maximum value of baseline DASI and linear regression for DASI scores less than
      maximum by means of bagging variable selection. RESULTS: Lower socioeconomic
      status was associated of lower risk-adjusted quality of life (maximum Duke
      Activity Status Index P = .0002, less than maximum Duke Activity Status Index P =
      .0007). Older age, female sex, certain comorbidities, higher New York Heart
      Association class, lower left ventricular function, and reoperation were also
      statistically significantly associated with lower preoperative Duke Activity
      Status Index. CONCLUSION: Lower socioeconomic status is associated with lower
      risk-adjusted quality of life for patients undergoing cardiac surgery. Quality of
      life affects morbid outcomes, so further characterization of risk factors for
      poor quality of life offers an opportunity for intervention.

PMID- 18805271
TI  - A new antispastic solution for arterial grafting: nicardipine and nitroglycerin
      cocktail in preparation of internal thoracic and radial arteries for coronary
      surgery.
AB  - OBJECTIVE: Antispastic protocols for arterial grafts are important in arterial
      grafting for coronary artery bypass grafting surgery. We designed a new
      nicardipine and nitroglycerin cocktail that is composed of a second-generation
      dihydropyridine calcium antagonist, nicardipine and nitroglycerin (30
      micromol/L), and examined its effect in human internal thoracic and radial
      arteries. METHODS: Human internal thoracic (n = 86) and radial (n = 74) artery
      segments from 72 patients undergoing coronary artery bypass grafting were
      studied. Relaxation against 3 classic vasoconstrictors (potassium chloride,
      thromboxane A(2) mimetic U46619, and alpha-adrenoceptor agonist norepinephrine)
      and prophylactic effect on contraction against these vasoconstrictors were
      examined. The effect of the nicardipine and nitroglycerin cocktail on the
      endothelial function in internal thoracic and radial arteries was studied in
      response to acetylcholine. RESULTS: Nicardipine and nitroglycerin induced almost
      full relaxation (92.2% +/- 4.7% to 97.9% +/- 1.0%, P < .001 in internal thoracic
      arteries and 95.4% +/- 1.9% to 96.7% +/- 3.3%, P < .001 in radial arteries, n = 6
      8) against 3 vasoconstrictors with significant prophylactic effect on contraction
      (maximal contraction was depressed to 32.5% to 76.4%, P < .05 or P < .001, and
      EC50s were increased to 5 to 42-fold more, P < .01). After treatment with the
      nicardipine and nitroglycerin cocktail, the acetylcholine-induced relaxation was
      unchanged (P > .05). CONCLUSION: The use of the nicardipine and nitroglycerin
      cocktail provides a new antispastic protocol that has rapid onset, full
      relaxation, and excellent prophylactic effect against all known mechanisms of
      vasospasm and maximally protects the endothelial and smooth muscle function of
      the internal thoracic and radial arteries. The cocktail is therefore expected to
      provide a new method in treating grafts in coronary artery bypass grafting with
      the best antispastic effect and protection of the graft.

PMID- 18805272
TI  - Neurologic sequelae of the donor arm after endoscopic versus conventional radial
      artery harvesting.
AB  - OBJECTIVE: Endoscopic radial artery harvesting remarkably improves cosmetic
      results after coronary artery bypass surgery. The aim of this study was to
      investigate neurologic sequelae of the donor arm compared with those occurring
      after the conventional harvesting technique. METHODS: Fifty-three patients who
      had undergone endoscopic radial artery harvesting were followed up 1 year after
      the coronary artery bypass operation by means of questionnaire analysis and
      clinical neurologic investigation (ENDO group). Fifty-three patients who had
      conventional radial artery harvesting during the same time frame served as
      control subjects (OPEN group). RESULTS: Postoperative wound revision was required
      in 4 patients of the OPEN group (P = .045 vs the ENDO group). Neurologic symptoms
      of the donor arm were present in 22 (OPEN group) versus 34 (ENDO group) patients
      (P = .020): a lesion of the superficial radial nerve was shown in 12 (OPEN group)
      versus 24 (ENDO) patients (P = .014), and a lesion of the lateral antebrachial
      cutaneous nerve occurred only in the control group in 12 patients (P < .001).
      Paraesthesia without impaired sensibility was present in 3 (OPEN group) versus 10
      (ENDO group) patients (P = .038). Clinical investigation revealed that
      temperature, pain, and touch sensation, as well as spatial discrimination, were
      equally impaired in symptomatic patients, whereas vibration sensation was not
      affected. CONCLUSION: After endoscopic radial artery harvesting, impaired
      sensibility in the region of the superficial radial nerve and paresthesia are
      more frequent than after the open procedure. However, in contrast to the sequelae
      of the open procedure, wound revision and injury of the lateral antebrachial
      cutaneous nerve did not occur. Because of the excellent cosmetic results and
      avoidance of wound complications, we have opted to use endoscopic radial artery
      harvesting as the technique of choice, despite the higher incidence of sensory
      disturbances.

PMID- 18805273
TI  - Aortic valve replacement with the Mitroflow pericardial bioprosthesis: durability
      results up to 21 years.
AB  - OBJECTIVE: The study aim was to analyze the performance profile of a large series
      of Mitroflow pericardial valves (Sorin Group Canada Inc. Mitroflow Division) in
      the very long term. METHODS: Data from 1513 patients with isolated aortic valve
      replacement who received pericardial bioprostheses between 1986 and 2007 were
      analyzed. Cumulative duration of follow-up was 6164 patient-years with a maximum
      duration of 21 years. Actuarial rates of valve-related events were calculated by
      the Kaplan-Meier method and the Cox multivariate analysis to identify independent
      determinants of outcome. RESULTS: Hospital mortality for elective surgery was
      2.5%. Late death was 40.6%. Reoperation was required in 86 (5.7%) patients and
      was valve related in 83: structural valve deterioration in 64 (4.2%) patients,
      prosthetic valve endocarditis in 17 patients (1.1%), valve thrombosis in 1, and
      periprosthetic leak in 1. Rates of 20-year actuarial freedom from valve-related
      morbidity were as follows: structural valve deterioration 84.8% (actual 96.6%) in
      patients 70 years of age or older; thromboembolism 94.1%; and prosthetic valve
      endocarditis 96.8%. Twenty-year actual risk of reoperation for structural valve
      deterioration was 11.4% in all patients and 3.4%, in patients 70 years or age or
      older. Advanced age, renal insufficiency, pulmonary disease, and low body mass
      index were independent risk factors for late outcome (P < .001). CONCLUSIONS:
      After 2 decades of follow-up, the Mitroflow pericardial aortic valve continues to
      be a valve of choice with a predictable low rate of valve-related events,
      particularly for patients over the age of 65 to 70 years and others with
      comorbidities.

PMID- 18805274
TI  - Surgical aortic valve replacement after percutaneous aortic valve implantation:
      what have we learned?
AB  - OBJECTIVE: We report the first case description of surgical aortic valve
      replacement after percutaneous valve implantation. METHODS: An 87-year-old man
      with severe aortic stenosis who was rejected for surgical intervention underwent
      percutaneous valve implantation through a retrograde femoral approach. The
      procedure was complicated by cardiogenic shock caused by severe aortic
      insufficiency, leading to emergency surgical aortic valve replacement. RESULTS:
      The operative findings revealed the presence of commissural paravalvular leaks
      and centrally malapposed leaflets. Surgical replacement was uneventful, and the
      patient was discharged on day 30, despite a challenging postoperative course. His
      follow-up at 1 year has been uneventful. This case illustrates that
      overdilatation of the stent is not recommended because it might worsen central
      aortic insufficiency. Moreover, the transapical route should be considered when
      the appropriately sized prosthesis is unable to be inserted because of
      inappropriate vascular access. However, despite an initial "prohibitive" surgical
      risk, surgical aortic valvular replacement after percutaneous valve implantation
      could be easily performed. CONCLUSION: Percutaneous heart valve implantation,
      which provides a larger surface area than balloon valvotomy, can be offered to
      patients with cardiogenic shock and severe comorbidities to improve their
      hemodynamic state and reduce their surgical risk.

PMID- 18805275
TI  - Simultaneous integrated coronary artery revascularization with long-term
      angiographic follow-up.
AB  - OBJECTIVE: Traditionally integrated coronary artery revascularization has been
      described as a 2-stage procedure. We evaluated the safety and feasibility of 1
      stage, simultaneous, hybrid, robotically assisted coronary artery bypass grafting
      surgery and percutaneous coronary intervention. METHODS: Fifty-eight patients
      underwent simultaneous, integrated coronary artery revascularization in an
      operating theater equipped with angiographic equipment. Forty-five patients were
      men. The mean age was 59 years. All internal thoracic arteries were harvested
      with robotic assistance. All anastomoses were manually constructed through a
      small anterior non-rib-spreading incision without cardiopulmonary bypass on the
      beating heart. Immediately after and within the same operative suite, both
      angiographic confirmation of graft patency and percutaneous coronary intervention
      were performed. In 52 patients therapeutic anticoagulation was achieved with the
      direct thrombin inhibitor bivalirudin. RESULTS: There were no deaths or wound
      infections. There was 1 perioperative myocardial infarction. One patient had a
      stroke, and 3 patients required re-exploration for bleeding. The median lengths
      of intensive care and hospital stay were 1 and 4 days, respectively. All patients
      were alive and symptom free at follow-up (mean, 20.2 months; range, 1.1-40.8
      months). Long-term angiographic follow-up in 54 patients showed 49 (91%) patent
      grafts (mean, 9.0 months; range, 4.3-40.8 months). There were 7 in-stent
      restenoses and 2 occluded stents. CONCLUSION: For multivessel coronary artery
      disease, simultaneous integrated coronary artery revascularization with
      bivalirudin is safe and feasible. This approach enables complete multivessel
      revascularization with decreased surgical trauma and postoperative morbidity.
      Further studies are necessary to better determine patient selection and long-term
      outcomes.

PMID- 18805276
TI  - Induction by left ventricular overload and left ventricular failure of the human
      Jumonji gene (JARID2) encoding a protein that regulates transcription and
      reexpression of a protective fetal program.
AB  - OBJECTIVE: We identified changes in Jumonji (JARID2) expression in failing human
      hearts and determined its effects on expressions of atrial natriuretic factor
      (ANF), myosin light chain 2a (MLC2A), and alpha myosin heavy chain (MHCA), genes
      associated with both human heart failure and the fetal gene program. METHODS:
      Left ventricular outflow tract cardiac biopsy samples were taken from 31 patients
      with aortic valvular stenosis. Hearts were grouped according to left ventricular
      size and function: nonfailing hearts (undilated with good function) and failing
      hearts (dilated with poor function). Protein levels were determined by Western
      blotting, and messenger RNA transcript levels by ratiometric reverse
      transcriptase-polymerase chain reaction. Luciferase assays in HL-2 cells were
      used to assess effects of Jarid2 on Anf, Mlc2a, and Mhca transcriptions.
      Chromatin immunoprecipitation was used to detect interaction of JARID2 with
      specific target-gene promoters. RESULTS: JARID2 and MHCA expressions were reduced
      in failing hearts, whereas MLC2A and ANF were increased. In HL-2 cell culture,
      Jarid2 suppressed Anf and Mlc2a but enhanced Mhca. Jarid2 expression was reduced
      by cyclic mechanical stress, with concomitant increased Anf and Mlc2a and
      decreased Mhca expressions, reproducing the expression profile found in
      decompensated human pressure overload. CONCLUSION: Jumonji expression is reduced
      by mechanical stress in human heart failure from aortic stenosis. JARID2
      regulates ANF, MLC2A, and MHCA transcription and contributes to reexpression of
      the fetal gene program in decompensated aortic stenosis. JARID2 appears important
      in transcriptional regulation of fetal genes and may emerge as a diagnostic
      marker for left ventricular decompensation in aortic stenosis.

PMID- 18805277
TI  - Constrictive external nitinol meshes inhibit vein graft intimal hyperplasia in
      nonhuman primates.
AB  - OBJECTIVE: External mesh support of vein grafts has been shown to mitigate the
      formation of intimal hyperplasia. The aim of the present study was to address the
      issue of optimal mesh size in a nonhuman primate model that mimics the
      dimensional mismatch typically encountered between clinical vein grafts and their
      target arteries. METHODS: The effect of mesh size on intimal hyperplasia and
      endothelial preservation was assessed in bilateral femoral interposition grafts
      in Chacma baboons (n(Sigma) = 32/n = 8 per mesh size). No mesh support (group I)
      was compared with external nitinol meshes at three different sizes: loose fitting
      (group II), 25% diameter constricting (group III), and 50% diameter constricting
      (group IV). Mesh sizes were seen not only in isolation but also against the
      background of anastomotic size mismatch at implantation, expressed as quotient of
      cross-sectional area of host artery to vein graft (Q(C)). RESULTS: Significant
      amounts of intimal hyperplasia were found in group I (Q(C) median 0.20; intimal
      hyperplasia 6 weeks = 1.63 +/- 0.34 mm(2); intimal hyperplasia 12 weeks = 1.73 +/
      0.5 mm(2)) and group II (Q(C) median 0.25; intimal hyperplasia 6 weeks = 1.96 +/
      1.64 mm(2); intimal hyperplasia 12 weeks = 2.88 +/- 1.69 mm(2)). In contrast,
      group III (Q(C) median 0.45; intimal hyperplasia 6 weeks = 0.08 +/- 0.13 mm(2);
      intimal hyperplasia 12 weeks = 0.18 +/- 0.32 mm(2)) and IV (Q(C) median 1.16;
      intimal hyperplasia 6 weeks = 0.02 +/- 0.03 mm(2); intimal hyperplasia 12 weeks =
      0.11 +/- 0.10 mm(2)) showed dramatically suppressed intimal hyperplasia (P < .01)
      at both time points. Endothelial integrity was only preserved in group IV (P <
      .05). There were no significant differences in vascularization and inflammation
      in either interlayer or intergroup comparisons. CONCLUSION: By using an animal
      model that addressed the clinical phenomenon of diameter discrepancy between vein
      graft and bypassed artery, we could demonstrate that suppression of intimal
      hyperplasia required constrictive mesh sizes.

PMID- 18805278
TI  - A methodology for assessing human mitral leaflet curvature using real-time 3
      dimensional echocardiography.
AB  - OBJECTIVES: Using 3-dimensional echocardiography in conjunction with novel
      geometric modeling and rendering techniques, we have developed a high-resolution,
      quantitative, 3-dimensional methodology for imaging the human mitral valve.
      Leaflet and annular geometry are important determinants of mitral valve stress.
      Repair techniques that optimize valvular geometry will reduce stress and
      potentially increase repair durability. The development of such procedures will
      require image-processing methodologies that provide a quantitative description of
      3-dimensional valvular geometry. METHODS: Ten healthy adult subjects underwent
      mitral valve imaging with real-time 3-dimensional echocardiography. By using
      specially designed image analysis software, multiple valvular geometric
      parameters, including 2- and 3-dimensional leaflet curvature, leaflet surface
      area, annular height, intercommissural width, septolateral annular diameter, and
      annular area were determined for each subject. Image-rendering techniques that
      allow for the clear and concise presentation of this detailed information are
      also presented. RESULTS: Although 3-dimensional annular and leaflet geometry were
      found to be highly conserved between healthy human subjects in general,
      substantial intrasubject and intersubject regional geometric heterogeneity was
      observed in the midposterior leaflet, the region most commonly involved in
      leaflet flail in subjects with myxomatous disease. CONCLUSIONS: The image
      processing and graphic-rendering techniques that we have developed can be used to
      provide a complete description of 3-dimensional mitral valve geometry in human
      subjects. Widespread application of these techniques to healthy subjects and
      patients with mitral valve disease will provide insight into the geometric basis
      of both valvular pathology and repair durability.

PMID- 18805279
TI  - Success and limitations of right ventricular sinus myectomy for pulmonary atresia
      with intact ventricular septum.
AB  - OBJECTIVES: Right ventricular sinus myectomy has been proposed for pulmonary
      atresia with intact ventricular septum for morphology falling within the
      uncertain area for eventual biventricular repair. Our objective was to evaluate
      right ventricular sinus myectomy by characterizing the morphologic spectrum of
      these patients, determining whether biventricular repair was achieved,
      ascertaining growth of right-sided structures, and assessing survival. METHODS:
      We evaluated medical records, all imaging studies, and follow-up data (complete
      in all but 1 patient) from 43 patients with pulmonary atresia with intact
      ventricular septum treated from October 1993 to July 2005, 16 of whom underwent
      right ventricular sinus myectomy. Serial echocardiographic measurements of right
      sided cardiac structures were converted to Z values to estimate their growth
      relative to somatic growth. RESULTS: Patients undergoing right ventricular sinus
      myectomy had mild-to-moderate right ventricular size diminution (grade -1.2 +/-
      3.2) and a tricuspid valve Z value of -4.9 +/- 1.9. Thirteen (87%) of the 16
      patients achieved biventricular repair. After right ventricular sinus myectomy,
      mean right ventricular cavity size grade increased to 1.4 +/- 0.66, but the
      tricuspid valve Z value did not change appreciably over time. Five-year survival
      after sinus myectomy was 85%; late deaths were in patients with the smallest
      tricuspid valves at presentation (Z value < -7). CONCLUSIONS: Right ventricular
      sinus myectomy in the uncertain area for biventricular repair of pulmonary
      atresia with intact ventricular septum leads to immediate increase in right
      ventricular volume. It, in combination with establishing right ventricle
      pulmonary trunk continuity, allowed early biventricular repair in 87% of
      patients. However, tricuspid valve growth in relation to somatic growth was
      minimal. Thus, small tricuspid valve size might limit the long-term success of
      biventricular repair achieved by means of right ventricular sinus myectomy.

PMID- 18805280
TI  - Does the degree of preoperative mitral regurgitation predict survival or the need
      for mitral valve repair or replacement in patients with anomalous origin of the
      left coronary artery from the pulmonary artery?
AB  - BACKGROUND: Anomalous origin of the left coronary artery from the pulmonary
      artery causes severe myocardial ischemia, global left ventricular dysfunction,
      and annular dilatation producing varying degrees of mitral regurgitation. Mitral
      regurgitation secondary to the left ventricular or papillary muscle dysfunction
      in infants will usually improve in the absence of ongoing ischemia. The aim of
      this study is to determine the influence of the degree of preoperative mitral
      regurgitation on the early and late outcomes of patients with anomalous origin of
      the left coronary artery from the pulmonary artery who underwent coronary
      reimplantation. METHODS: Twenty-five patients underwent coronary reimplantation
      and 1 early patient had ligation during a 30-year period (median age, 4 months;
      range, 1 month to 16 years), with a median follow-up of 7 years (range, 4 months
      to 25 years). Before repair, 7 infants (27%) presented in extremis requiring
      ventilatory and inotropic support, and 17 patients (65%) presented with heart
      failure. Mitral regurgitation was present in all patients: trivial in 6 patients,
      mild in 12 patients, moderate in 5 patients, and severe in 3 patients. No patient
      underwent mitral valve repair or replacement at the time of anomalous origin of
      the left coronary artery from the pulmonary artery repair. RESULTS: Hospital
      survival was 92%. Three patients underwent mitral valve repair or replacement at
      the mean time of 3.5 years (all with severe preoperative mitral regurgitation).
      The degree of mitral regurgitation gradually improved in all remaining patients
      with preoperative mild and moderate mitral regurgitation. Echocardiographic
      studies demonstrated improvement in left ventricular function in all children.
      None of the patients showed any evidence of supravalvar pulmonary stenosis as a
      result of their pulmonary artery reconstruction. CONCLUSION: Long-term clinical
      outcome and left ventricular function are good despite severe left ventricular
      dysfunction at presentation. Mitral valve repair or replacement is generally not
      necessary at the time of anomalous origin of the left coronary artery from the
      pulmonary artery repair. Significant residual mitral regurgitation is present in
      some patients and can usually be managed surgically at a later date depending on
      its degree of severity.

PMID- 18805281
TI  - Treatment of right ventricle to coronary artery connections in infants with
      pulmonary atresia and intact ventricular septum.
AB  - OBJECTIVE: At the severe end of the spectrum of infants with pulmonary atresia
      and intact ventricular septum, the likelihood of significant right ventricle to
      coronary artery connections increases. Our purpose is to present the first series
      of right ventricle to coronary artery connections ligated off bypass before right
      ventricular decompression and to evaluate the consequences of this approach.
      METHODS: From 1988 to 2007, 19 patients with pulmonary atresia and intact
      ventricular septum had a total of 69 right ventricle to coronary artery
      connections identified preoperatively, and 10 more were located intraoperatively.
      Of these, 71 were judged large enough to warrant off-pump direct ligation.
      Preoperative diagnosis was by transthoracic echocardiography and angiography.
      Transesophageal and surface echocardiography were used for intraoperative
      location. Direct visualization and echocardiographic assessment for regional wall
      motion abnormalities determined the effects of ligation. Right ventricular
      decompression was done in all patients. RESULTS: After ligation, coronary flow
      converted from moderately or largely retrograde to antegrade perfusion. Ligation
      produced no visual myocardial consequences or immediate local wall motion
      abnormalities. For 3 patients, however, apical-septal wall motion abnormalities
      appeared from 2 hours to 3 days postoperatively. Serial studies were done to
      assess the later effects in the 16 of 19 30-day survivors. No evidence for
      myocardial injury was found, and all continued on a 2-ventricle repair course.
      CONCLUSION: The location and ligation of right ventricle to coronary artery
      connections can be reliably accomplished off bypass. Coronary flow became
      antegrade, improving myocardial oxygenation. No myocardial damage was observed.
      Inapparent right ventricle to coronary artery connections occasionally enlarge
      secondarily after right ventricular decompression, making early follow-up
      evaluation necessary after ligation. Despite the initial presence of significant
      right ventricle to coronary artery connections, 2-ventricle repairs are possible
      with long-term benefits.

PMID- 18805282
TI  - Role of fibrillin-1 genetic mutations and polymorphism in aortic dilatation in
      patients undergoing intracardiac repair of tetralogy of Fallot.
AB  - OBJECTIVE: The purposes of this study were to identify the occurrence of
      fibrillin-1 gene polymorphisms or mutations in exons 24 to 28 and to identify the
      relationship between "DNA sequence variants" and aortic dilatation in the
      presence of abnormal aortic histopathology and other variables in patients
      undergoing intracardiac repair of tetralogy of Fallot. METHODS: Operatively
      excised full-thickness aortic wall tissue and 5 to 10-mL venous blood samples
      from 74 consecutive patients undergoing intracardiac repair of tetralogy of
      Fallot were studied. Histopathologic evaluation was done by light microscopy.
      Polymerase chain reaction amplification of fibrillin-1 gene was carried out for 5
      exons (24-28), and amplified products were subjected to single-strand
      conformation polymorphism analysis to identify sequence alterations, if any.
      Logistic regression analysis was done to identify the relationship between
      patients with and without "exonic DNA variants" with other risk factors causing
      aortic dilatation. RESULTS: Sixteen aortic tissue specimens (21.6%) were
      indicated as histologically normal and used as controls. Of 51 patients with
      dilated aorta, 48 (94.1%) exhibited histologic abnormalities. The incidences of
      significant lamellar loss, abnormal histopathology, and fibrillin-1 "DNA sequence
      variants" in tetralogy of Fallot with dilated aorta were 78.4%, 96.1%, and 50.9%,
      respectively. The risk of aortic dilatation was 8.83 (1.94-13.99) times greater
      in patients with histologically abnormal aorta and 8.11 (1.93-34.04) times
      greater in patients with fibrillin-1 "exonic DNA variants." CONCLUSION: Our
      findings indicate the existence of "exonic DNA variants" involving the fibrillin
      1 gene in 1 or more exons (exon 24-28). The "DNA sequence variants" are more
      pronounced in patients with tetralogy of Fallot and dilated aorta in the presence
      of abnormal aortic histopathology.

PMID- 18805283
TI  - Outcome of high-risk neonates with congenital complete heart block paced in the
      first 24 hours after birth.
AB  - OBJECTIVE: Risk factors for poor outcome with congenital complete heart block
      include prematurity, low birth weight, hydrops, low ventricular rates, and
      congenital heart disease. In this group, medical therapy is often ineffective,
      pacing is technically challenging, and mortality exceeds 80%. The purpose of this
      study is to assess outcomes of patients with congenital complete heart block who
      were paced in the first 24 hours after birth owing to the presence of known risk
      factors. METHODS: We performed a retrospective review of patients with congenital
      complete heart block paced in the first 24 hours after birth at our institution
      between November 1, 1995, and July 31, 2007. RESULTS: Thirteen patients were
      identified, 4 of whom had heterotaxy syndrome. Eleven patients had temporary
      epicardial pacing wires placed; 2 received permanent pacemakers as the initial
      mode of pacing. There were 7 deaths (54% mortality) at a mean age of 19.9 +/- 19
      days. Among 7 patients with structural heart disease, there was 1 survivor. Among
      6 patients with structurally normal hearts, there were 5 survivors (P = .025).
      Patients with temporary wires who survived to permanent pacemaker implantation
      (6/11) used their temporary leads for 33.8 +/- 18.3 days. CONCLUSIONS: In the
      severely affected fetus with congenital complete heart block and significant
      structural heart disease, outcomes remain poor; however, neonates with congenital
      complete heart block and structurally normal hearts who are monitored antenatally
      and delivered in a planned fashion at an institution capable of early pacing can
      have favorable outcomes. The use of temporary pacing wires is an option in the
      management of these patients.

PMID- 18805284
TI  - Left ventricular assist device as bridge to transplantation does not adversely
      affect one-year heart transplantation survival.
AB  - OBJECTIVE: Left ventricular assist devices are increasingly used as a bridge to
      transplantation. It remains unclear whether the use of pretransplant left
      ventricular assist devices adversely affects short-term survival after cardiac
      transplantation. METHODS: A retrospective review of 317 consecutive patients
      undergoing cardiac transplantation at an academic center between 1986 and 2006
      was undertaken. Left ventricular assist devices were used pretransplant in 23 of
      these 317 patients, and 294 patients did not require left ventricular assist
      device support. Patients with a left ventricular assist device were supported
      with a Heartmate VE or Heartmate XVE (Thoratec Corp, Pleasanton, Calif). Kaplan
      Meier survival estimates were compared between the left ventricular assist device
      group and the non-left ventricular assist device group using the log-rank test.
      In addition, occurrence of death was analyzed between the 2 groups with a chi
      square analysis. The results are expressed as 1-year survival with 95% confidence
      intervals in parentheses. RESULTS: The 1-year survival for all 317 patients was
      0.86 (0.82-0.90). The patient survival for the group without a left ventricular
      assist device before cardiac transplant was 0.87 (0.83-0.90), and the survival
      for the group with a left ventricular assist device as bridge to transplantation
      was 0.83 (0.67-0.98; P = .77). For the deaths that occurred in all 317 patients,
      19% of the patients without left ventricular assist devices died within 30 days
      of transplant, whereas 80% of the patients with left ventricular assist devices
      died within 30 days of transplant (P < .01). CONCLUSION: When used as a bridge to
      transplantation, left ventricular assist devices do not compromise 1-year
      survival after cardiac transplantation. Of the patients who die after
      transplantation, patients bridged with left ventricular assist devices are at
      higher risk for death within 30 days of transplant. These data suggest that left
      ventricular assist devices as a bridge to transplantation should be considered
      for appropriately selected patients awaiting cardiac transplantation.

PMID- 18805285
TI  - Placental transmogrification of the lung presenting as tension pneumothorax: case
      report with review of literature.

PMID- 18805286
TI  - Surgical correction of postpneumonectomy-like syndrome in a patient with a
      tuberculosis-destroyed lung.

PMID- 18805287
TI  - Nonoperative management of large tracheal injuries.

PMID- 18805288
TI  - Cardiac development after salvage partial left ventriculectomy in an infant with
      anomalous left coronary artery from the pulmonary artery.

PMID- 18805289
TI  - Surgical extraction of cardiac resynchronization therapy system with concomitant
      implantation of a new system with the use of epicardial leads in a patient with
      endocarditis.

PMID- 18805290
TI  - Aberrant left coronary artery arising from the right sinus of Valsalva: case
      reports of a rare entity.

PMID- 18805291
TI  - The extended pectoralis major flap for reconstruction of the upper posterior
      chest wall and axilla.

PMID- 18805292
TI  - Intraoperative coronary angiography in the management of patients with acute
      aortic dissection and endocarditis.

PMID- 18805293
TI  - Novel use of an aortic endograft in the closure of a Fontan circuit leak.

PMID- 18805295
TI  - Management of spinal cord perfusion pressure to minimize intermediate-delayed
      paraplegia: critical role of central venous pressure.

PMID- 18805296
TI  - Cardiac stem cells in the real world.

PMID- 18805297
TI  - Aprotinin; an economy of truth?

PMID- 18805300
TI  - Interaction between theory and experiment in the study of sleep physiology: a
      historical survey of early sleep research.
AB  - The interaction between theory and experiment in sleep research was considered on
      the grounds of a selective historical survey of early sleep studies up to the
      first half of the twentieth century. The dialectic pair of experimental
      reductionism and theoretical holism was the motor of progress in sleep research
      as soon as it was supported by the electroencephalographic technique, a by
      product of applied physics. The identification of sleep stages was a turning
      point in the development of the experimental methodology of sleep research. Also,
      other scientific disciplines, particularly anatomy and chemistry, provided
      technical support increasingly suitable for the experimental study of the
      physiology and pathology of sleep. In general, cognitive advances depended on a
      research methodology (theoretical and experimental) free from the influence of
      cultural prejudices and supposedly indisputable scientific paradigms.

PMID- 18805301
TI  - [Narcolepsy with cataplexy].
AB  - Narcolepsy is a rare, disabling sleep disorder, with a prevalence of 20 to 30 per
      100,000. Its onset, from childhood to the fifties, peaks in the second decade.
      The main features are excessive daytime sleepiness and cataplexy or sudden loss
      of muscle tone triggered by emotional situations. Other less consistent symptoms
      include hypnagogic hallucinations, sleep paralysis, sleep maintenance insomnia,
      REM sleep behavior disorders, attention deficit and weight gain at disease onset.
      Narcolepsy with cataplexy remains a clinical diagnosis but nighttime and daytime
      polysomnography (multiple sleep latency tests) are useful to document a mean
      sleep latency below 8 min and at least two sleep-onset REM periods. HLA typing
      shows an association with HLA DQB1*0602 in more than 92% of cases but was not
      included in the new diagnostic criteria. In contrast, a low hypocretin levels
      (values below 110 pg/ml) in the cerebrospinal fluid (CSF) was highly specific for
      narcolepsy with cataplexy. The deficiency of the hypocretin system is well
      established in animal models of narcolepsy (murine and canine narcolepsy) but
      also in human narcoleptics with a 90% reduction of CSF hypocretin levels in
      relation with an early loss of hypocretin neurons. The cause of human narcolepsy
      remains unknown, however an autoimmune process is most probable. The treatment of
      narcolepsy includes stimulants against sleepiness (modafinil, methylphenidate),
      anticataplectic drugs (antidepressants) and sodium oxybate. The current
      therapeutic target is oriented towards hypocretine agonists, histamine (an
      arousal system) H3 antagonists and immunosuppressants.

PMID- 18805302
TI  - [REM sleep behavior disorders and their characteristics in Parkinson's disease].
AB  - REM sleep behavior disorders (RBD) are vigorous, complex movements corresponding
      to enacted dreams. They may disturb sleep, and injure the patients or their bed
      partner. RBD are frequently associated with neurodegenerative diseases,
      especially synucleopathies. They can precede parkinsonism or dementia by five to
      10 years. These presymptomatic RBDs are frequently associated with EEG slowing,
      reduced olfaction, mild visuospatial cognitive impairment, and decreased dopamine
      transport in functional brain imaging. In Parkinson's disease, 15 to 60% patients
      speak, laugh, shout, kick, punch or fight invisible enemies during REM sleep. In
      contrast to sleepwalkers, patients with RBD rarely stand up or walk, but can fall
      out of bed. Sleep monitoring indicates an imperfect abolition of muscle tone
      during REM sleep in these patients. RBD are probably caused by nondopaminergic
      pontine lesions in the REM sleep atonia system. This condition may also expose
      patients with Parkinson's disease to a higher risk of daytime and nighttime
      hallucinations, and to more frequent cognitive impairment. Interestingly, several
      spouses reported that they observed a sharp contrast between the slow, limited
      movements, and poorly intelligible, low voice of their affected spouse when
      awake, and the fast, vigorous movements with loud voice that the very same
      patient exhibited during enacted dreams. We recently demonstrated that
      parkinsonism indeed disappears during RBD, in a large study combining the
      interview of 100 couples and the sleep and video monitoring of 50 patients. The
      mechanism of this improvement is now being explored.

PMID- 18805303
TI  - Fatal insomnia and agrypnia excitata: sleep and the limbic system.
AB  - Fatal familial insomnia, a human prion disease, Morvan's chorea, an autoimmune
      limbic encephalopathy, and delirium tremens, the well-known alcohol (or
      benzodiazepine [BDZ]) withdrawal syndrome, share a clinical phenotype largely
      consisting in an inability to sleep associated with motor and autonomic
      activation. Agrypnia excitata is the term which aptly defines this clinical
      condition, whose pathogenetic mechanism consists in an intralimbic disconnection
      releasing the hypothalamus and brainstem reticular formation from corticolimbic
      inhibitory control. Severance of cortical-subcortical limbic structures is due to
      visceral thalamus degeneration in fatal familial insomnia, and may depend on
      autoantibodies blocking voltage-gated potassium channels within the limbic system
      in Morvan's chorea, and the sudden changes in gabaergic synapses down-regulated
      by chronic alcohol abuse within the limbic system in delirium tremens. On the
      basis of these findings, we suggest that a neuronal network, extending from the
      medulla to the limbic cortex, controls the sleep-wake cycle, operating in an
      integrated fashion following a caudorostral organization.

PMID- 18805304
TI  - [POEMS syndrome with plasmocytoma lytic bone lesion].
AB  - INTRODUCTION: Crow-Fukase or Polyneuropathy, Organomegaly, Endocrinopathy, M
      protein, and Skin changes syndrome (POEMS) is a rare multisystemic affection with
      incompletely elucidated etiopathogenesis. CASE REPORT: We report a case of POEMS
      syndrome in a 48-year-old adult revealed four months before admission by
      areflexic flask tetraparesis prevalent on the lower limbs in connection with
      demyelinating and axonal CIDP "like" sensoriomotor neuropathy of the four limbs
      electroneuromyographically. The patient presented elevated protein level in the
      CSF with monoclonal standard IgG gammapathy associated with a narrow band lambda,
      suggesting POEMS syndrome. Further explorations revealed skin lesions with
      glomeruloid angiomas, edematous vasomotor disorders as well as erythrocyanose,
      hypogonadism, papillar edema and a lytic bone lesion of the left scapula.
      Radiotherapy was associated with corticosteroids and plasma exchanges. Outcome
      was good with resolution of the symptoms and stabilization of the neuropathy.
      DISCUSSION: POEMS syndrome is rare; the diagnosis is based on necessary criteria,
      the presence of a demyelinating and axonal polyneuropathy associated with an IgA
      or IgG monoclonal gammapathy, the light chain being almost entirely lambda,
      associated to other characteristic elements, in particular glomeruloid angiomas,
      endocrinopathy, sclerosing plasmocytoma which must be carefully required.
      Treatment is based on surgical cure or radiotherapy for bone lesion and non
      specific treatments such as corticosteroid therapy, plasma exchanges and IVIG.

PMID- 18805305
TI  - [Stroke and iridodonesis revealing a homocystinuria caused by a compound
      heterozygous mutation of cystathionine beta-synthase].
AB  - Iridodonesis or tremulous iris is a clinical sign of ectopia lentis which is
      frequently associated with homocystinuria. We present a forty-two-year-old woman
      victim of a left middle cerebral artery ischemic stroke. The clinical examination
      found bilateral iridodonesis and laboratory tests showed an increased level of
      serum homocysteine and homocystinuria. Homocystinuria was caused by a compound
      heterozygous I278T and D444N mutation of cystathionine beta-synthase (CBS) gene
      and also a C667T heterozygous polymorphism of methylene-tetrahydrofolate
      reductase gene. This case was atypical because of the incomplete phenotype,
      development of complications in adulthood and the association of a rare compound
      heterozygous mutation of the CBS gene.

PMID- 18805306
TI  - [Actinomycosis: an unusual cause of spinal cord compression. Case report and
      review of the literature].
AB  - Actinomycosis is an unusual and unrecognized cause of spinal cord compression of
      infectious origin. We report the case of a 57-year-old immunocompetent woman
      admitted for sub-acute lower limb ataxia. The diagnosis of spinal cord
      compression secondary to actinomyces infectious arthritis was established.
      Surgical decompression and long-term antibiotic treatment enabled complete
      recovery. Data from the literature indicate that actinomycosis is a potential
      cause of several neurological manifestations. Unusual but treatable,
      actinomycosis is a potential alternative when the main etiologies have been ruled
      out.

PMID- 18805307
TI  - [Professional guidelines for the diagnosis and management of Alzheimer's disease
      and related diseases, HAS (Haute Autorite de Sante) 2008].

PMID- 18805308
TI  - Asthma: still more questions than answers.

PMID- 18805309
TI  - More money for cancer, but no more battles.

PMID- 18805310
TI  - Mental-health services: a disturbing situation.

PMID- 18805311
TI  - Does paracetamol cause asthma in children? Time to remove the guesswork.

PMID- 18805312
TI  - Rhinitis as predictor of adult-onset asthma.

PMID- 18805313
TI  - Transition from childhood to adult asthma.

PMID- 18805314
TI  - Exhaled nitric oxide in guideline-based asthma management.

PMID- 18805315
TI  - Inflammometry to assess airway diseases.

PMID- 18805316
TI  - Severe childhood asthma: a common international approach?

PMID- 18805317
TI  - The coming of age of asthma guidelines.

PMID- 18805318
TI  - Erika von Mutius: reshaping the landscape of asthma research.

PMID- 18805319
TI  - Isolated systolic blood pressure measurement.

PMID- 18805320
TI  - Isolated systolic blood pressure measurement.

PMID- 18805323
TI  - Thrombus aspiration during percutaneous coronary intervention.

PMID- 18805321
TI  - Isolated systolic blood pressure measurement.

PMID- 18805324
TI  - Thrombus aspiration during percutaneous coronary intervention.

PMID- 18805325
TI  - Secondary prevention of stroke.

PMID- 18805326
TI  - Hyperglycaemia as a cardiovascular risk factor in diabetes.

PMID- 18805327
TI  - Secondary prevention of stroke.

PMID- 18805329
TI  - Thromboprophylaxis for patients at high risk of VTE.

PMID- 18805330
TI  - Management of allergic rhinitis.

PMID- 18805331
TI  - Studying medicine with a criminal record.

PMID- 18805332
TI  - Association between paracetamol use in infancy and childhood, and risk of asthma,
      rhinoconjunctivitis, and eczema in children aged 6-7 years: analysis from Phase
      Three of the ISAAC programme.
AB  - BACKGROUND: Exposure to paracetamol during intrauterine life, childhood, and
      adult life may increase the risk of developing asthma. We studied 6-7-year-old
      children from Phase Three of the International Study of Asthma and Allergies in
      Childhood (ISAAC) programme to investigate the association between paracetamol
      consumption and asthma. METHODS: As part of Phase Three of ISAAC, parents or
      guardians of children aged 6-7 years completed written questionnaires about
      symptoms of asthma, rhinoconjunctivitis, and eczema, and several risk factors,
      including the use of paracetamol for fever in the child's first year of life and
      the frequency of paracetamol use in the past 12 months. The primary outcome
      variable was the odds ratio (OR) of asthma symptoms in these children associated
      with the use of paracetamol for fever in the first year of life, as calculated by
      logistic regression. FINDINGS: 205 487 children aged 6-7 years from 73 centres in
      31 countries were included in the analysis. In the multivariate analyses, use of
      paracetamol for fever in the first year of life was associated with an increased
      risk of asthma symptoms when aged 6-7 years (OR 1.46 [95% CI 1.36-1.56]). Current
      use of paracetamol was associated with a dose-dependent increased risk of asthma
      symptoms (1.61 [1.46-1.77] and 3.23 [2.91-3.60] for medium and high use vs no
      use, respectively). Use of paracetamol was similarly associated with the risk of
      severe asthma symptoms, with population-attributable risks between 22% and 38%.
      Paracetamol use, both in the first year of life and in children aged 6-7 years,
      was also associated with an increased risk of symptoms of rhinoconjunctivitis and
      eczema. INTERPRETATION: Use of paracetamol in the first year of life and in later
      childhood, is associated with risk of asthma, rhinoconjunctivitis, and eczema at
      age 6 to 7 years. We suggest that exposure to paracetamol might be a risk factor
      for the development of asthma in childhood.

PMID- 18805333
TI  - Rhinitis and onset of asthma: a longitudinal population-based study.
AB  - BACKGROUND: A close relation between asthma and allergic rhinitis has been
      reported by several epidemiological and clinical studies. However, the nature of
      this relation remains unclear. We used the follow-up data from the European
      Community Respiratory Health Survey to investigate the onset of asthma in
      patients with allergic and non-allergic rhinitis during an 8.8-year period.
      METHODS: We did a longitudinal population-based study, which included 29 centres
      (14 countries) mostly in western Europe. Frequency of asthma was studied in 6461
      participants, aged 20-44 years, without asthma at baseline. Incident asthma was
      defined as reporting ever having had asthma confirmed by a physician between the
      two surveys. Atopy was defined as a positive skin-prick test to mites, cat,
      Alternaria, Cladosporium, grass, birch, Parietaria, olive, or ragweed.
      Participants were classified into four groups at baseline: controls (no atopy, no
      rhinitis; n=3163), atopy only (atopy, no rhinitis; n=704), non-allergic rhinitis
      (rhinitis, no atopy; n=1377), and allergic rhinitis (atopy+rhinitis; n=1217). Cox
      proportional hazards models were used to study asthma onset in the four groups.
      FINDINGS: The 8.8-year cumulative incidence of asthma was 2.2% (140 events), and
      was different in the four groups (1.1% (36), 1.9% (13), 3.1% (42), and 4.0% (49),
      respectively; p<0.0001). After controlling for country, sex, baseline age, body
      mass index, forced expiratory volume in 1 s (FEV(1)), log total IgE, family
      history of asthma, and smoking, the adjusted relative risk for asthma was 1.63
      (95% CI 0.82-3.24) for atopy only, 2.71 (1.64-4.46) for non-allergic rhinitis,
      and 3.53 (2.11-5.91) for allergic rhinitis. Only allergic rhinitis with
      sensitisation to mite was associated with increased risk of asthma independently
      of other allergens (2.79 [1.57-4.96]). INTERPRETATION: Rhinitis, even in the
      absence of atopy, is a powerful predictor of adult-onset asthma.

PMID- 18805334
TI  - Wheezing and bronchial hyper-responsiveness in early childhood as predictors of
      newly diagnosed asthma in early adulthood: a longitudinal birth-cohort study.
AB  - BACKGROUND: Incidence of asthma increases during early adulthood. We aimed to
      estimate the contributions of sex and early life factors to asthma diagnosed in
      young adults. METHODS: 1246 healthy newborn babies were enrolled in the Tucson
      Children's Respiratory Study. Parental characteristics, early-life wheezing
      phenotypes, airway function, and bronchial hyper-responsiveness to cold dry air
      and sensitisation to Alternaria alternata were determined before age 6 years.
      Physician-diagnosed asthma, both chronic and newly diagnosed, and airway function
      were recorded at age 22 years. FINDINGS: Of 1246 babies enrolled, 849 had follow
      up data at 22 years. Average incidence of asthma at age 16-22 years was 12.6 per
      thousand person-years. 49 (27%) of all 181 cases of active asthma at 22 years
      were newly diagnosed, of which 35 (71%) were women. Asthma remittance by 22 years
      was higher in men than in women (multinomial odds ratio [M-OR] 2.0, 95% CI 1.2
      3.2, p=0.008). Age at diagnosis was linearly associated with the ratio of forced
      expiratory volume at 1 s to forced vital capacity at age 22 years. Factors
      independently associated with chronic asthma at 22 years included onset at 6
      years (7.4, 3.9-14.0) and persistent wheezing (14.0, 6.8-28.0) in early life,
      sensitisation to A alternata (3.6, 2.1-6.4), low airway function at age 6 years
      (2.1, 1.1-3.9), and bronchial hyper-responsiveness at 6 years (4.5, 1.9-10.0).
      Bronchial hyper-responsiveness (6.9, 2.3-21.0), low airway function at 6 years
      (2.8, 1.1-6.9), and late-onset (4.6, 1.7-12.0) and persistent wheezing (4.0, 1.2
      14.0) predicted newly diagnosed asthma at age 22 years. INTERPRETATION: Asthma
      with onset in early adulthood has its origins in early childhood.

PMID- 18805336
TI  - New targets for drug development in asthma.
AB  - Asthma is a chronic inflammatory disease that affects about 300 million people
      worldwide, a total that is expected to rise to about 400 million over the next 15
      20 years. Most asthmatic individuals respond well to the currently available
      treatments of inhaled corticosteroids and beta-adrenergic agonists; however, 5
      10% have severe disease that responds poorly. Improved knowledge of asthma
      mechanisms has led to the recognition of different asthma phenotypes that might
      reflect distinct types of inflammation, explaining the effectiveness of anti
      leucotrienes and the anti-IgE monoclonal antibody omalizumab in some patients.
      However, more knowledge of the inflammatory mechanisms within the airways is
      required. Improvements in available therapies-such as the development of fast
      onset, once-a-day combination drugs with better safety profiles-will occur. Other
      drugs, such as inhaled p38 MAPK inhibitors and anti-oxidants, that target
      specific pathways or mediators could prove useful as monotherapies, but could
      also, in combination with corticosteroids, reduce the corticosteroid
      insensitivity often seen in severe asthma. Biological agents directed against the
      interleukin-13 pathway and new immunoregulatory agents that modulate functions of
      T-regulatory and T-helper-17 cells are likely to be successful. Patient-specific
      treatments will depend on the development of discriminatory handprints of
      distinct asthma subtypes and are probably over the horizon. Although a cure is
      unlikely to be developed in the near future, a greater understanding of disease
      mechanisms could bring such a situation nearer to reality.

PMID- 18805335
TI  - Management of asthma based on exhaled nitric oxide in addition to guideline-based
      treatment for inner-city adolescents and young adults: a randomised controlled
      trial.
AB  - BACKGROUND: Preliminary evidence is equivocal about the role of exhaled nitric
      oxide (NO) in clinical asthma management. We aimed to assess whether measurement
      of exhaled NO, as a biomarker of airway inflammation, could increase the
      effectiveness of asthma treatment, when used as an adjunct to clinical care based
      on asthma guidelines for inner-city adolescents and young adults. METHODS: We did
      a randomised, double-blind, parallel-group trial at ten centres in the USA. We
      screened 780 inner-city patients, aged 12-20 years, who had persistent asthma.
      All patients completed a run-in period of 3 weeks on a regimen based on standard
      treatment. 546 eligible participants who adhered to treatment during this run-in
      period were then randomly assigned to 46 weeks of either standard treatment,
      based on the guidelines of the National Asthma Education and Prevention Program
      (NAEPP), or standard treatment modified on the basis of measurements of fraction
      of exhaled NO. The primary outcome was the number of days with asthma symptoms.
      We analysed patients on an intention-to-treat basis. This trial is registered
      with clinicaltrials.gov, number NCT00114413. FINDINGS: During the 46-week
      treatment period, the mean number of days with asthma symptoms did not differ
      between the treatment groups (1.93 [95% CI 1.74 to 2.11] in the NO monitoring
      group vs 1.89 [1.71 to 2.07] in the control group; difference 0.04 [-0.22 to
      0.29], p=0.780). Other symptoms, pulmonary function, and asthma exacerbations did
      not differ between groups. Patients in the NO monitoring group received higher
      doses of inhaled corticosteroids (difference 119 mug per day, 95% CI 49 to 189,
      p=0.001) than controls. Adverse events did not differ between treatment groups
      (p>0.1 for all adverse events). INTERPRETATION: Conventional asthma management
      resulted in good control of symptoms in most participants. The addition of
      fraction of exhaled NO as an indicator of control of asthma resulted in higher
      doses of inhaled corticosteroids, without clinically important improvements in
      symptomatic asthma control.

PMID- 18805337
TI  - Complexity of chronic asthma and chronic obstructive pulmonary disease:
      implications for risk assessment, and disease progression and control.
AB  - Although assessment of asthma control is important to guide treatment, it is
      difficult since the temporal pattern and risk of exacerbations are often
      unpredictable. In this Review, we summarise the classic methods to assess control
      with unidimensional and multidimensional approaches. Next, we show how ideas from
      the science of complexity can explain the seemingly unpredictable nature of
      bronchial asthma and emphysema, with implications for chronic obstructive
      pulmonary disease. We show that fluctuation analysis, a method used in
      statistical physics, can be used to gain insight into asthma as a dynamic disease
      of the respiratory system, viewed as a set of interacting subsystems (eg,
      inflammatory, immunological, and mechanical). The basis of the fluctuation
      analysis methods is the quantification of the long-term temporal history of lung
      function parameters. We summarise how this analysis can be used to assess the
      risk of future asthma episodes, with implications for asthma severity and control
      both in children and adults.

PMID- 18805339
TI  - Endotyping asthma: new insights into key pathogenic mechanisms in a complex,
      heterogeneous disease.
AB  - Clinical asthma is very widely assumed to be the net result of excessive
      inflammation driven by aberrant T-helper-2 (Th2) immunity that leads to inflamed,
      remodelled airways and then functional derangement that, in turn, causes
      symptoms. This notion of disease is actually poorly supported by data, and there
      are substantial discrepancies and very poor correlation between inflammation,
      damage, functional impairment, and degree of symptoms. Furthermore, this problem
      is compounded by the poor understanding of the heterogeneity of clinical disease.
      Failure to recognise and discover the underlying mechanisms of these major
      variants or endotypes of asthma is, arguably, the major intellectual limitation
      to progress at present. Fortunately, both clinical research and animal models are
      very well suited to dissecting the cellular and molecular basis of disease
      endotypes. This approach is already suggesting entirely novel pathways to disease
      eg, alternative macrophage specification, steroid refractory innate immunity, the
      interleukin-17-regulatory T-cell axis, epidermal growth factor receptor co
      amplification, and Th2-mimicking but non-T-cell, interleukins 18 and 33 dependent
      processes that can offer unexpected therapeutic opportunities for specific
      patient endotypes.

PMID- 18805338
TI  - Early identification of atopy in the prediction of persistent asthma in children.
AB  - The long-term solution to the asthma epidemic is thought to be prevention, and
      not treatment of established disease. Atopic asthma arises from gene-environment
      interactions, which mainly take place during a short period in prenatal and
      postnatal development. These interactions are not completely understood, and
      hence primary prevention remains an elusive goal. We argue that primary-care
      physicians, paediatricians, and specialists lack knowledge of the role of atopy
      in early life in the development of persistent asthma in children. In this
      review, we discuss how early identification of children at high risk is feasible
      on the basis of available technology and important for potential benefits to the
      children. Identification of an asthmatic child's atopic status in early life has
      practical clinical and prognostic implications, and sets the basis for future
      preventative strategies.

PMID- 18805340
TI  - No fire without smoke.

PMID- 18805341
TI  - Quiz page. October 2008. Tumoral calcinosis, with cystic cavities within a
      fibromuscular stroma that are filled with granular calcific material. Cyst walls
      consist of foamy histiocytes and multinucleated giant cells.

PMID- 18805342
TI  - Predicting outcomes in CKD.

PMID- 18805343
TI  - Variations in levels of blood pressure: of prognostic value or not?

PMID- 18805344
TI  - Normalization of hemoglobin in patients with CKD may cause harm: but what is the
      mechanism?

PMID- 18805345
TI  - Reporting estimated GFR: a laboratory perspective.

PMID- 18805346
TI  - Dialysis dosing in critically ill patients with acute kidney injury.

PMID- 18805347
TI  - Variability and risk factors for kidney disease progression and death following
      attainment of stage 4 CKD in a referred cohort.
AB  - BACKGROUND: The outcomes of patients referred to nephrologists are not well
      described in large cohorts. The objectives of this analysis are to describe the
      predictors of rapid progression of kidney disease and death in patients followed
      up by nephrologists. STUDY DESIGN: Retrospective study. SETTING & PARTICIPANTS: A
      cohort derived from all patients registered in the provincial database was formed
      that included all patients with index estimated glomerular filtration rate (eGFR)
      less than 30 mL/min/1.73 m(2), at least 3 subsequent eGFR values, and 4 months of
      follow-up between January 2000 and January 2004. PREDICTORS: Variables used to
      predict outcomes included baseline eGFR, duration of follow-up before eGFR less
      than 30 mL/min/1.73 m(2), age, sex, ethnicity, presence of diabetes, blood
      pressure, level of proteinuria, hemoglobin level, phosphate level, calcium level,
      parathyroid hormone level, and use of angiotensin-converting enzyme inhibitors or
      angiotensin receptor blockers, erythropoiesis-stimulating agents, and vitamin D.
      OUTCOMES: Key outcomes of interest were death, dialysis therapy start, or loss of
      GFR greater than 5 mL/min/1.73 m(2)/y. RESULTS: 4,231 patients met inclusion
      criteria. Mean age was 67 years. Median follow-up was 31 months. During the first
      2 years of follow-up, 24% started dialysis therapy, 1% received a transplant, 7%
      died, and 1% was lost to follow-up. Statistically significant variables
      associated with more rapid kidney disease progression differ from those that
      predict death. Younger age, male sex, higher eGFR, higher systolic and diastolic
      blood pressure, lower hemoglobin level, higher phosphorus and parathyroid hormone
      levels, and greater proteinuria are associated with more rapid kidney disease
      progression, and use of angiotensin-converting enzymes/angiotensin receptor
      blockers are protective. Older age, lower diastolic blood pressure, lower
      hemoglobin level, and higher phosphorous and parathyroid hormone levels are
      associated with death, whereas vitamin D use is protective. LIMITATIONS: Results
      cannot be generalized to unreferred patients with eGFR less than 30 mL/min/1.73
      m(2). CONCLUSION: The clinical course of patients with chronic kidney disease
      stage 4 is variable. Targeted therapy aimed at modifiable risk factors needs to
      be evaluated to determine benefits of this approach.

PMID- 18805348
TI  - Etiology and clinical characteristics of membranous nephropathy in Chinese
      patients.
AB  - BACKGROUND: Membranous nephropathy (MN) is a common cause of proteinuria and can
      be subdivided into idiopathic and secondary classifications. Most patients with
      MN present with associated systemic diseases that need to be identified before
      appropriately diagnosing idiopathic MN. However, the cause and clinical
      characteristics of MN in Chinese patients have not been investigated. STUDY
      DESIGN: Case series. SETTING & PARTICIPANTS: Patients with biopsy-proven MN at
      the Research Institute of Nephrology, Jinling Hospital, Nanjing University School
      of Medicine, Nanjing, China. OUTCOME: The diagnosis of idiopathic and secondary
      MN was based on clinical, initial laboratory, and histological findings. RESULTS:
      390 patients with MN were identified from 1985 to 2005. Of 390 patients with MN,
      124 (31.8%) had idiopathic MN and 266 had secondary MN (68.2%). Of patients with
      idiopathic MN, 75 (60.5%) were men and 49 (39.5%) were women. Mean age was 43.9
      +/- 13.2 years (range, 14 to 78 years). Common presentations of idiopathic MN
      were 60.5% with proteinuria (39.5% of whom presented with nephrotic syndrome),
      29.8% with hypertension, 17.7% with hematuria, and 0.8% with decreased kidney
      function. In patients with secondary MN, causes were autoimmune diseases (73.3%),
      infections (17.7%), tumors (4.5%), and drugs or toxins (4.5%). Systemic lupus
      erythematosus was the most common autoimmune disease (predominately in younger
      women). Hepatitis B predominated in younger men. Greater levels of proteinuria
      were found in patients who presented with drugs or toxins compared with patients
      with other secondary MNs (P < 0.05). LIMITATIONS: Not all patients underwent all
      tests, particularly serum tumor markers, hepatitis C virus antibody, and
      hepatitis C virus RNA tests. CONCLUSION: Proteinuria was a common presentation in
      patients with idiopathic MN, which was predominately found in middle-aged to
      elderly men. Secondary MN was more common than idiopathic MN, and most secondary
      MN diagnoses were secondary to systemic lupus erythematosus and hepatitis B
      infection.

PMID- 18805350
TI  - CKD in the elderly.

PMID- 18805351
TI  - The beneficial effect of oral calcitriol treatment on proteinuria in IgA
      nephropathy: another point of view.

PMID- 18805352
TI  - Pharmacodynamics of unfractionated heparin during and after a hemodialysis
      session: the impact of the administered dose.

PMID- 18805356
TI  - Interpretation of birth weight data: a note of caution.

PMID- 18805357
TI  - Acute renal failure due to a primary renal B-cell lymphoma.

PMID- 18805359
TI  - Leigh and Leigh-like syndrome in children and adults.
AB  - Leigh syndrome (also termed subacute, necrotizing encephalopathy) is a
      devastating neurodegenerative disorder, characterized by almost identical brain
      changes, e.g., focal, bilaterally symmetric lesions, particularly in the basal
      ganglia, thalamus, and brainstem, but with considerable clinical and genetic
      heterogeneity. Clinically, Leigh syndrome is characterized by a wide variety of
      abnormalities, from severe neurologic problems to a near absence of
      abnormalities. Most frequently the central nervous system is affected, with
      psychomotor retardation, seizures, nystagmus, ophthalmoparesis, optic atrophy,
      ataxia, dystonia, or respiratory failure. Some patients also present with
      peripheral nervous system involvement, including polyneuropathy or myopathy, or
      non-neurologic abnormalities, e.g., diabetes, short stature, hypertrichosis,
      cardiomyopathy, anemia, renal failure, vomiting, or diarrhea (Leigh-like
      syndrome). In the majority of cases, onset is in early childhood, but in a small
      number of cases, adults are affected. In the majority of cases, dysfunction of
      the respiratory chain (particularly complexes I, II, IV, or V), of coenzyme Q, or
      of the pyruvate dehydrogenase complex are responsible for the disease. Associated
      mutations affect genes of the mitochondrial or nuclear genome. Leigh syndrome and
      Leigh-like syndrome are the mitochondrial disorders with the largest genetic
      heterogeneity.

PMID- 18805360
TI  - Anxiety and depressive symptoms in children presenting with a first seizure.
AB  - We investigated whether children presenting with a first seizure experienced
      anxiety and depressive signs. Children (aged 7-17 years) with a first unprovoked
      afebrile seizure participated. These patients (mean age, 12 +/- 2.7 years S.D.;
      14 female/8 male) completed the Revised Child Manifest Anxiety Scale (n = 22) and
      Children's Depression Inventory (n = 20). Scores were compared with: (1)
      published norms, and (2) control patients with new medical signs. Compared with
      the published norms, children reported greater total anxiety (P < 0.02),
      worry/oversensitivity (P < 0.008), and social concerns/concentration (P < 0.005).
      However, compared with the control patients, no difference was seen between
      groups. Total Children's Depression Inventory scores were higher than for
      published norms (P = 0.05) and control patients (P = 0.04). Children with a first
      seizure reported greater interpersonal problems (P < 0.01), ineffectiveness (P <
      0.03), and negative self-esteem (P < 0.05) than published norms, and increased
      negative mood (P = 0.04), ineffectiveness (P = 0.04), anhedonia (P = 0.05), and
      negative self-esteem (P = 0.05) than control patients. Our results suggest that
      anxiety may be related to an illness or to the hospital experience itself,
      whereas depressive signs may be a comorbidity present at time of presentation of
      the first seizure. If a larger cohort substantiates these results, early
      screening for these signs would be of clinical importance.

PMID- 18805361
TI  - Role of apolipoprotein E in febrile convulsion.
AB  - Apolipoprotein E is consistently associated with the progression of some common
      human neurodegenerative diseases, e.g., epilepsy. We hypothesized that genetic
      variations in the apolipoprotein E gene have implications for susceptibility to,
      and prognoses in, febrile convulsion, which plays an apparent role in the
      development of epilepsy. We used the polymerase chain reaction and restriction
      enzyme digestion to characterize variations of the apolipoprotein E gene. Sixty
      nine patients with febrile convulsion (simple/complex) and a corresponding cohort
      of healthy patients (n = 75) were used. There was no significant difference in
      genotypic distribution and allelic frequencies of the apolipoprotein E gene
      between the febrile convulsion and control groups. Comparing subpopulations of
      the febrile convulsion group (patients with simple and complex febrile
      convulsion), we noted that no patients with the epsilon3/epsilon4 genotype had
      complex febrile convulsions. The apolipoprotein E epsilon3/epsilon4 genotype was
      more frequently seen in the simple febrile than in the complicated febrile
      convulsion group (9 versus 0 patients, respectively). The data indicate an
      association with the epsilon3/epsilon4 genotype of the apolipoprotein E gene with
      a milder phenotype. Although apolipoprotein E4 is not a vulnerability factor
      regarding febrile convulsions, it seems effective in regard to prognoses.

PMID- 18805362
TI  - Tau and S100B proteins as biochemical markers of bilirubin-induced neurotoxicity
      in term neonates.
AB  - We investigated the relationship between total serum bilirubin and serum Tau and
      S100B protein levels, and predicted a cutoff level of bilirubin-induced
      neurotoxicity in term newborns. Total serum bilirubin, serum Tau, and S100B
      levels were measured in 92 jaundiced term newborns. A neurologic examination,
      electroencephalogram, brainstem auditory-evoked response, and otoacoustic
      emission were performed in the infants on admission and at age 3 months. Serum
      Tau (r = 0.921, P < 0.001) and S100B (r = 0.927, P < 0.001) levels were
      correlated with total serum bilirubin levels in all infants. Serum Tau and S100B
      protein levels remained at a steady level up to a total serum bilirubin level of
      19.1 mg/dL, and then demonstrated a significant increase. Mean total serum
      bilirubin, serum Tau, and S100B levels of infants who manifested auditory
      neuropathy, neurologic abnormalities, or electroencephalogram abnormalities were
      significantly higher than in infants without these abnormalities (P < 0.05).
      Clinical and laboratory findings of bilirubin-induced neurotoxicity developed
      after a total serum bilirubin level of 22 mg/dL was reached. Serum levels of Tau
      and S100B proteins in jaundiced term newborns were strongly correlated with early
      phase bilirubin encephalopathy.

PMID- 18805363
TI  - Prospective study examining remote effects of botulinum toxin a in children with
      cerebral palsy.
AB  - We examined the remote effects on muscle strength and functional decline of lower
      extremity botulinum toxin A injections in children with cerebral palsy. This
      prospective study enrolled 34 children (19 boys, 15 girls; mean age, 7.7 years)
      diagnosed with spastic cerebral palsy. Patients were examined at baseline and 1
      month to determine if they experienced a change in upper-extremity strength
      (handheld dynamometry) or function (Pediatric Outcomes Data Collection
      Instrument). Subjects were analyzed in aggregate and by dosing group (low dose, 0
      10 U/kg body weight; high dose, 11-25 U/kg) to determine if injection dose was
      associated with a change in remote muscle strength or function. We measured
      baseline and 1-month postinjection strength in shoulder flexor, shoulder
      abductor, elbow flexor, elbow extensor, and finger flexor muscles. None of these
      remote muscle groups was significantly weaker at 1 month after injection. No
      correlation was evident between change in muscle strength and toxin dose. These
      findings indicate that doses of botulinum toxin A in the lower extremities, at up
      to 21 U/kg, do not affect upper-extremity strength. This information can help
      guide dosages of botulinum toxin A in the management of spasticity in children
      with cerebral palsy.

PMID- 18805364
TI  - Movement disorder-childhood rating scale: reliability and validity.
AB  - A new scale for children and adolescents aged 4-18 years, called the Movement
      Disorder Childhood Rating Scale, was designed to: (1) describe clinical features
      of different types of movement disorders; (2) evaluate the intensity of movement
      disorders in different body regions at rest and during specific tasks; and (3)
      assess the influence of movement disorders on motor function and daily living
      activities. The scale is divided into 2 parts: Part I for general assessment, and
      Part II for movement-disorder severity. It includes a 20-minute standardized
      video protocol of all items. The scale was applied to 61 patients with different
      types of movement disorder, and was independently scored by 3 observers.
      Reliability, construct validity, and consistency indexes are reported. High
      interrater agreement on each item, and a high degree of internal consistency on
      several proposed items, were evident.

PMID- 18805365
TI  - Evaluation of bone turnover in epileptic children using oxcarbazepine.
AB  - This study evaluated the effects of oxcarbazepine monotherapy on bone turnover in
      prepubertal and pubertal children. Thirty-four newly diagnosed pediatric patients
      with normal bone mineral density, serum biochemical markers of bone formation,
      and hormonal markers participated. Levels of 25-hydroxyvitamin D were
      significantly decreased after therapy compared with baseline values. Levels of
      gamma-glutamyl transferase, phosphorus, alkaline phosphatase, osteocalcin,
      parathyroid hormone, and calcitonin had increased. However, only changes in
      osteocalcin and gamma-glutamyl transferase levels were statistically significant
      compared with baseline values. Drug-induced osteopenia was evident in 3 patients
      with z scores of bone-mineral density less than -2.0, whereas these patients had
      z scores of less than -1.5 before treatment. Although 18 months of oxcarbazepine
      treatment exerted slightly adverse effects on bone metabolism, the effect seems
      insignificant in children with normal bone-mineral density. Although alterations
      in bone metabolism do not always suffice to explain the decrease in bone-mineral
      metabolism, we think that patients with osteopenia before the initiation of
      oxcarbazepine therapy should be followed carefully, especially in long-term
      treatment.

PMID- 18805366
TI  - Idiopathic intracranial hypertension in a child after hemodialysis.
AB  - Idiopathic intracranial hypertension remains a disease of unknown etiology.
      Epidemiology, associations, features, and prognosis in children have changed over
      the years. The main clinical complaint of pediatric idiopathic intracranial
      hypertension is headache with visual disturbance. We report on a patient with
      childhood idiopathic intracranial hypertension, who presented without headache
      after hemodialysis for acute renal failure. Idiopathic intracranial hypertension
      without headache is believed to have a poor prognosis. However, this child
      demonstrated a favorable outcome with medical therapy. The child was followed
      with serial optical coherence tomography of retinal nerve fiber layer thickness
      around the optic nerve head. In the absence of a reliable procedure to evaluate
      the therapeutic efficacy in the follow-up of patients with idiopathic
      intracranial hypertension, the importance of optical coherence tomography, a
      noninvasive, objective, and reproducible procedure, is highlighted as a useful
      adjunct in the management of idiopathic intracranial hypertension.

PMID- 18805367
TI  - Infantile myofibromatosis: a nontraumatic cause of neonatal brachial plexus
      palsy.
AB  - Most injuries to the neonatal brachial plexus occur acutely at birth, and are
      iatrogenic in origin. However, when weakness is accompanied by atrophy,
      nontraumatic etiologies should be considered. The differential diagnosis of
      chronic congenital brachial plexopathy includes cervical bone malformations,
      humeral osteomyelitis, varicella, and compression from various types of infantile
      tumors. An illustrative male infant delivered at 37 weeks of gestation with
      wasted musculature of the left upper arm, ipsilateral Horner's syndrome, and a
      hemidiaphragm is presented. On further examination, this patient manifested an
      underlying cervical tumor compressing the brachial plexus. Diagnostic steps
      leading to the pathologic identification of a solitary cervical myofibroma
      included physical examination, electromyography, radiographic imaging, and open
      biopsy. This report emphasizes the importance of differentiating acute from
      chronic congenital plexus palsy and of recognizing the possibility that infection
      or neoplasm may underlie the latter.

PMID- 18805368
TI  - Acquired obstructive hydrocephalus in globoid-cell leukodystrophy.
AB  - Acquired obstructive hydrocephalus has developed rarely in patients with globoid
      cell leukodystrophy. This report describes a 21-month-old female with this
      concurrence.

PMID- 18805369
TI  - Cystic white-matter changes in childhood Wilson's disease.
AB  - Altered signals in magnetic resonance imaging are present in most symptomatic
      patients with neurologic manifestations of Wilson's disease. The changes
      primarily involve the basal ganglia, but they can be diverse and can involve a
      host of other structures. We describe a 12-year-old boy with Wilson's disease who
      manifested prominent white-matter cystic changes. These changes can cause
      diagnostic confusion, and may also present prognostic implications.

PMID- 18805370
TI  - Epidermal nevus syndrome with azygos anterior cerebral artery.
AB  - Epidermal nevus syndrome is a neurocutaneous disorder characterized by the
      association of epidermal nevi with central nervous system or skeletal
      abnormalities. Central nervous system abnormalities include hemimegalencephaly,
      hydrocephalus, various migration disorders, intraspinal lipomas, and enlarged
      spinal roots. Rarely, vascular anomalies cause neurologic signs. We report on a
      30-month-old girl with epidermal nevus syndrome who also exhibited vascular
      malformations of the azygos anterior cerebral artery, a cortical aneurysm, and
      right internal carotid artery hypoplasia. This rare vascular abnormality was not
      previously reported in patients with epidermal nevus syndrome.

PMID- 18805371
TI  - Pontocerebellar hypoplasia type 1.
AB  - Pontocerebellar hypoplasias are heterogeneous disorders that share a reduction in
      the size of brainstem and cerebellum. We describe a patient with features of the
      rare combination of pontocerebellar hypoplasia and spinal motor neuron disease.
      Parental consanguinity, low Apgar scores, facial weakness, dysphagia, tongue
      fasciculations, stridor, generalized hypotonia, severe muscle weakness,
      areflexia, and congenital joint contractures were evident. Cranial magnetic
      resonance imaging revealed a small cerebellum and brainstem, and a muscle biopsy
      revealed neurogenic changes. These abnormalities suggested pontocerebellar
      hypoplasia type 1.

PMID- 18805372
TI  - De novo ABCD1 gene mutation in an Indian patient with adrenoleukodystrophy.
AB  - A large number of ABCD1 gene mutations have been reported all over the world, but
      not previously in India. We report on the first known patient with childhood
      cerebral adrenoleukodystrophy and a de novo 3' splice-site mutation in this gene.
      Magnetic resonance imaging of the brain revealed large, confluent, hyperintense
      areas in the bilateral cerebral white matter, predominantly parieto-occipital,
      with extensions into posterior regions that led to breakdown of the blood-brain
      barrier. An increased level of very long chain fatty acids was also consistent
      with the biochemical defect for adrenoleukodystrophy. Sequencing of the ABCD1
      gene of this patient identified a 3' splice-site mutation in the intervening
      sequence 4 (-2a > g). We did not find any mutation in the gene of the proband's
      mother, which confirms its de novo occurrence.

PMID- 18805373
TI  - Anti-phospholipid antibodies in cerebrospinal fluid but not serum from a boy with
      psychosis.
AB  - A 12-year-old African American boy with mental retardation and Asperger's
      disorder presented with acute psychosis. Antiphospholipid antibody testing with
      enzyme-linked immunosorbent assay showed increased levels of immunoglobulin G
      anticardiolipin antibodies in the cerebrospinal fluid, but not in the serum.
      Although antiphospholipid antibodies have been reported in the serum of patients
      with thrombotic and neurologic disorders, there are only a few reports of these
      antibodies in cerebrospinal fluid. This finding is consistent with a recent
      report of antiphospholipid antibodies found in the cerebrospinal fluid of adults
      with acute psychosis.

PMID- 18805374
TI  - Neurofibromatosis type 1 with intracranial hemorrhage and horseshoe kidney.
AB  - A 12-year-old boy presented with a history of sudden-onset vomiting, headache,
      and giddiness. Two members of his family manifested neurofibromatosis type 1. On
      examination, the child had multiple cafe-au-lait spots, bilateral axillary
      freckles, and Lisch nodules in both eyes. A central nervous system examination
      revealed raised intracranial pressure. Computed tomography of the cranium
      revealed an intracranial hemorrhage in the right parietal region, without a
      midline shift. Magnetic resonance imaging of the brain revealed a hemorrhage and
      a neurofibromatosis bright object. Magnetic resonance angiography and digital
      subtraction angiography revealed no evidence of arteriovenous malformation or
      aneurysm. Ultrasonography of the abdomen revealed a horseshoe kidney, as
      confirmed by a 99m technetium dimercaptosuccinic acid renal cortical scan. He
      responded to treatment for the raised intracranial pressure, and remained
      asymptomatic during follow-up.

PMID- 18805375
TI  - Oxcarbazepine in nocturnal frontal-lobe epilepsy: a further interesting report.

PMID- 18805377
TI  - Vascular disease and chronic kidney disease. Editorial.

PMID- 18805378
TI  - The impact of systemic calcified atherosclerosis in patients with chronic kidney
      disease.

PMID- 18805379
TI  - New insights into stroke in chronic kidney disease.
AB  - Patients with chronic kidney disease (CKD) are predisposed to stroke, especially
      as the estimated glomerular filtration rate decreases. This update reviews the
      pathologic mechanisms particular to this stroke population. The treatment for
      primary and secondary prevention of stroke is reviewed with respect to
      antiplatelet agents, anticoagulants, surgery, and carotid stenting. The control
      of chronic hypertension is particularly important in reducing stroke risk in CKD.
      In patients with prior stroke from atherosclerosis, antiplatelet agents are most
      beneficial in reducing secondary stroke risk. Those with atrial fibrillation and
      CKD may benefit from warfarin anticoagulation. Statins in CKD for stroke
      reduction in diabetics receiving dialysis are not useful, and the data are
      pending for their use in stroke reduction in the general CKD population. In
      carefully selected cases, carotid endarterectomy can be a treatment. The data on
      carotid stenting are conflicting.

PMID- 18805380
TI  - Outcomes of carotid revascularization in patients with chronic kidney disease.
AB  - Chronic kidney disease (CKD) carries an increased risk for cardiovascular disease
      (CVD) including cerebrovascular accidents (CVAs). There are multiple etiologies
      for CVA, and among them extracranial carotid artery disease accounts for
      approximately 25% of ischemic strokes. It has been shown that carotid
      revascularization by carotid endarterectomy and carotid artery angioplasty and
      stenting can decrease the risk of CVA in appropriately selected population with
      carotid artery disease. Both these techniques of carotid revascularization have
      been shown to be safe and clinically effective in many large multicentered
      randomized clinical trials. However, most of these large trials have
      predominately excluded the patients with kidney failure. Most of the evidence for
      the management of carotid disease in CKD is based on small clinical trials and
      expert opinions. There is an urgent need to conduct large clinical trials in
      patients with CKD to enable better understanding and to improve techniques of
      various carotid revascularization therapies in CKD patients.

PMID- 18805381
TI  - Renal artery stenosis and chronic ischemic nephropathy: epidemiology and
      diagnosis.
AB  - Atherosclerotic renal artery stenosis (RAS) is the most common primary disease of
      the renal arteries and results in renovascular hypertension and ischemic
      nephropathy. Ischemic nephropathy from atherosclerotic RAS is increasingly
      recognized as a cause of chronic kidney disease (CKD) and in severe cases can
      lead to end-stage renal disease. The exact prevalence of atherosclerotic RAS is
      unknown because the disease is often asymptomatic and few are screened unless
      they have significant traditional cardiac risk factors or symptoms. A high
      prevalence of atherosclerotic RAS is seen in patients with advanced age,
      congestive heart failure, and extrarenal atherosclerosis. The primary reason for
      diagnosing ischemic nephropathy from renovascular disease is that the loss of
      kidney function is potentially reversible through treatment of the occlusion with
      surgical revascularization or percutaneous transluminal renal angioplasty.
      However, the benefits of revascularization have to be considered in the context
      of other comorbid disease and remain controversial. There are several tests
      available for the screening and diagnosis of atherosclerotic RAS; however, the
      diagnostic test of choice should be based on patient factors and institutional
      expertise because the best test is the one performed most often at the individual
      medical facility.

PMID- 18805382
TI  - Renal artery revascularization: collaborative approaches for specialists.
AB  - Endovascular revascularization for atherosclerotic renal artery stenosis (RAS) is
      the revascularization strategy of choice for patients with hemodynamically and
      clinically significant renal artery stenosis. Surgical revascularization is
      reserved for failed endovascular therapy or concomitant abdominal aortic surgery.
      Endovascular renal artery stenting is associated with excellent technical
      success, low complication rates, and acceptable long-term patency. This technique
      has been proven to be beneficial for preserving kidney function and stabilizing
      or improving blood pressure control in selected patients. Nevertheless,
      deterioration in kidney function after the procedure in 10% to 20% of cases may
      limit the immediate benefits of this technique. Atheroembolism appears to play an
      important role in the cause of kidney dysfunction after renal revascularization.
      Renal revascularization with a distal embolic protection device is a promising
      strategy in reducing the risk of atheroembolism and deterioration in kidney
      function.

PMID- 18805383
TI  - Risks and benefits of antiplatelet therapy in uremic patients.
AB  - Patients with renal insufficiency are at an increased risk for cardiovascular
      morbidity and mortality. Despite being at a substantial risk for thrombotic
      events, patients with renal insufficiency also experience a greater number of
      hemorrhagic complications associated with antiplatelet therapy than individuals
      with normal renal function. This review focuses on the benefits and risks of
      antiplatelet therapy in patients with impaired kidney function suffering from an
      acute coronary syndrome.

PMID- 18805384
TI  - Epidemiology and diagnosis of peripheral arterial disease in patients with
      chronic kidney disease.
AB  - Chronic kidney disease (CKD) and peripheral arterial disease (PAD) are common and
      frequently coexist. Among subjects with CKD, arterial disease may be due to
      atherosclerosis, medial arterial calcification (MAC), or both conditions
      concomitantly. It is important for clinicians to recognize both conditions
      because each identifies individuals at higher risk of cardiovascular disease
      events, and because the presence of MAC complicates interpretation of the ankle
      brachial index, the most commonly used diagnostic test for artherosclerotic PAD.
      To that end, we review the epidemiology and diagnosis of atherosclerotic PAD and
      medical arterial calcification in patients with CKD.

PMID- 18805385
TI  - Interventional management of critical limb ischemia in renal patients.
AB  - Critical limb ischemia (CLI) represents the most severe clinical manifestation of
      peripheral arterial disease (PAD), defined as the presence of chronic ischemic
      rest pain, ulcers, or gangrene attributable to objectively proven arterial
      occlusive disease. The occurrence of CLI in patients with kidney insufficiency
      portends a strikingly high rate of subsequent morbidity and mortality. Generally,
      the primary therapy for CLI is revascularization of the affected limb. However,
      patients with CLI and kidney insufficiency represent a unique and challenging
      patient subset, and data from surgical series suggest reduced rates of limb
      salvage and higher medium and long-term mortality rates for patients with kidney
      insufficiency compared with those with normal kidney function. In contemporary
      practice, endovascular techniques are fast replacing surgical bypass as the first
      line revascularization strategy for CLI, based on high technical success rates
      and low rates of procedure-related morbidity and mortality. However, a large
      series on endovascular outcomes for the treatment of CLI in patients with kidney
      insufficiency is lacking. Based on the severely reduced long-term survival rates
      of patients with CLI and kidney insufficiency, future efforts should focus on
      early detection of PAD in patients with kidney insufficiency and institution of
      aggressive medical therapy to prevent progression in the global burden of
      atherosclerosis in this patient population.

PMID- 18805386
TI  - Amplification of atherosclerotic calcification and Monckeberg's sclerosis: a
      spectrum of the same disease process.
AB  - Autopsy studies have shown the near universal presence of fatty streaks and
      fibroatheromas in the general population from which chronic kidney disease (CKD)
      patients arise. The vast majority of CKD patients have multiple conventional
      cardiovascular risk factors. Atherosclerosis, once present, can predominantly
      manifest as medial calcification, which has been previously termed Monckeberg's
      sclerosis. This term has also been used in rare cases to describe vascular
      calcinosis not related to CKD. This clarification is critical to advance the
      field in terms of pathological diagnosis and treatment of CKD bone and mineral
      disorder. Factors that appear to promote the osteoblastic transformation of
      vascular smooth muscle cells and enhance deposition of calcium hydroxyapatite
      crystals include phosphorus activation of the Pit-1 receptor, bone morphogenic
      proteins 2 and 4, leptin, endogenous 1,25 dihydroxy vitamin D, vascular
      calcification activating factor, and measures of oxidative stress. These entities
      work to accelerate the atherosclerotic process in CKD patients and may be future
      targets for diagnosis and treatment. Although conventional atherosclerotic risk
      factors should be optimally managed, it should be noted that trials of
      hydroxymethylglutaryl-CoA reductase inhibitors have failed to attenuate the rate
      of progressive vascular calcification as measured by computed tomography scans.

PMID- 18805387
TI  - Vascular calcification in uremia: what is new and where are we going?
AB  - Arterial calcification is very common in patients with chronic kidney disease
      (CKD) and other chronic inflammatory disorders such as diabetes mellitus.
      Arterial calcification is associated with significant morbidity and increased
      early mortality. Vascular calcification is a highly orchestrated process that
      entrains a repertoire of transcription factors and involves the activation of an
      osteogenic program that recapitulates the molecular fingerprints seen in bone
      formation. Recent studies have implicated the inflammatory cytokine tumor
      necrosis factor alpha in the pathobiology of arterial calcification. Metabolic
      acidosis, which is prevalent in patients with advanced kidney disease, has also
      been shown in some recent studies to attenuate vascular calcification in animal
      models. In this review, we summarize the recent advances in understanding the
      molecular mechanisms underpinning vascular mineralization and discuss their
      implications in terms of translational opportunities, unmet needs, and future
      directions.

PMID- 18805388
TI  - Anaemia in advanced chronic fasciolosis.
AB  - The association between fasciolosis-induced anaemia and related factors has been
      quantified in a rodent model. Haematological parameters were analysed in Wistar
      rats at 20 and 60 weeks post-infection (p.i.). Pigment stones and bile specimens
      were collected. Serum IgG1, IgG2a and IgE were determined in rat serum samples.
      Cytokine levels have been correlated with haematological parameters. The
      screening for gastrointestinal bleeding was carried out. Bacteriological bile
      cultures revealed viable bacteria in 53.8% of specimens at 60 weeks p.i. The
      results show that the type of anaemia in fasciolosis might be considered a
      biomarker of the chronicity period of the disease, changing from normocytic to
      macrocytic in the early chronic period (20 weeks p.i.) and to microcytic in the
      advanced chronic period (60 weeks p.i.). Likewise, changing from normochromic in
      the early chronic period to hypochromic in the advanced chronic period.
      Multivariate analysis suggested an association between anaemia and the following
      factors: fluke burden, eggs per gram of faeces, body area of parasite, presence
      of blood in faeces, IgG1 and eosinophil levels, and % of splenic weight. Of all
      variables analysed, the fluke burden is the one which presents the highest
      anaemia risk, even exceeding the variable presence of blood in faeces. The
      development of anaemia appears to be complex and may involve multiple mechanisms.
      However, to the mechanisms that until now explain Fascioliosis-related anaemia
      (compensatory increase in erythrocyte production and a continuous drain on iron
      stores resulting from the parasites' blood-sucking activities) the following
      causes ought to be added: haemolysis of red blood cells, the general effects of
      inflammation on erythropoiesis, concomitant parasitic and bacterial infections
      and pre-morbid nutritional abnormalities. Extrapolation to human fasciolosis is
      discussed. The results of the rodent model lead to the assumption that a high
      risk of anaemia in subjects with a heavy parasitic burden in human hyperendemic
      areas of fasciolosis is to be expected.

PMID- 18805389
TI  - An easy assay for histone acetyltransferase activity using a PhosphorImager.
AB  - A simple radiometric assay for histone acetyltransferase (HAT) activity employing
      a PhosphorImager is described. In the proposed procedure, following incubation of
      [1-(14)C]acetyl coenzyme A (CoA), histones, and HAT enzyme, radiolabeled histones
      are fixed on GF/F glass microfiber filter while the excess of acetyl CoA is
      washed out. Afterward, the filter is exposed to a phosphor-screen and the
      resulting spot signals are quantified with a PhosphorImager. Given the small
      volumes required, the new assay reduces reagent consumption and contaminated
      waste. Moreover, the assay can be performed with a large number of samples
      simultaneously, is applicable on different protein substrates, and is adaptable
      to the analysis of other protein modifications.

PMID- 18805390
TI  - In situ analysis of plant tissue underivatized carbohydrates and on-probe
      enzymatic degraded starch by matrix-assisted laser desorption/ionization time-of
      flight mass spectrometry by using carbon nanotubes as matrix.
AB  - Underivatized carbohydrates of tulip bulb and leaf tissues were characterized in
      situ by matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry (MALDI-TOF MS) by using carbon nanotubes (CNTs) as matrix. Two
      sample preparation methods--(i) depositing CNTs on the fresh tissue slices placed
      on the probe and (ii) locating semitransparent tissues on a dried layer of CNTs
      on the probe--were examined. Furthermore, practicability of in situ starch
      analysis by MALDI-TOF MS was examined by detection of glucose originated from on
      probe amyloglucosidase-catalyzed degradation of starch on the tissue surface.
      Besides, CNTs could efficiently desorb/ionize natural mono-, di-, and
      oligosaccharides extracted from tulip bulb tissues as well as glucose resulting
      from starch enzymatic degradation in vitro. These results were compared with
      those obtained by in situ MALDI-TOF MS analysis of similar tissues. Positive ion
      mode showed superior signal reproducibility. CNTs deposited under semitransparent
      tissue could also desorb/ionize neutral carbohydrates, leading to nearly complete
      elimination of matrix cluster signals but with an increase in tissue-originated
      signals. Furthermore, several experiments were carried out to compare the
      efficiency of 2,5-dihydroxybenzoic acid, nor-harmane, alpha-cyano-4
      hydroxycinnamic acid, and CNTs as matrices for MALDI of neutral carbohydrates
      from the intact plant tissue surface and for enzymatic tissue starch degradation;
      these results are discussed in brief. Among matrices studied, the lowest laser
      power was needed to acquire carbohydrate signals with high signal-to-noise ratio
      and resolution when CNTs were used.

PMID- 18805391
TI  - A maxi-chloride channel in the inner membrane of mammalian mitochondria.
AB  - Patch-clamp experiments on swollen mitochondria of human, mouse and rat origins
      have revealed activity by an approximately 400 pS (in 150 mM KCl), voltage
      dependent and anion-selective channel. This channel is located in the inner
      membrane, as shown by experiments with mitochondria from cells expressing a
      fluorescent mitochondrial tag protein and by the co-presence of the 107 pS
      channel and of the permeability transition pore (PTP). The frequency of
      appearance was inversely related to the presence of the PTP. This and the
      comparison of its electrophysiological characteristics with those of the PTP
      indicate that it is closely related to the latter, possibly corresponding to a
      monomeric unit whose dimer constitutes the full PTP. The channel is similar but
      not identical to isolated-and-reconstituted mitochondrial porin, and it is
      present also in mitochondria from cells lacking porin isoforms. Its
      identification with porin is therefore to be excluded. It most likely coincides
      instead with the "maxi-chloride channel" characterized in the plasma membrane of
      various cell types.

PMID- 18805392
TI  - Phase diagrams and lipid domains in multicomponent lipid bilayer mixtures.
AB  - Understanding the phase behavior of biological membranes is helped by the study
      of more simple systems. Model membranes that have as few as 3 components exhibit
      complex phase behavior that can be well described, providing insight for
      biological membranes. A number of different studies are in agreement on general
      findings for some compositional phase diagrams, in particular, those that model
      the outer leaflet of animal cell plasma membranes. These model mixtures include
      cholesterol, together with one high-melting lipid and one low-melting lipid. An
      interesting finding is of two categories of such 3-component mixtures, leading to
      what we term Type I and Type II compositional phase diagrams. The latter have
      phase regions of macroscopic coexisting domains of [Lalpha+Lbeta+Lo] and of
      [Lalpha+Lo], with domains resolved under the light microscope. Type I mixtures
      have the same phase coexistence regions, but the domains seem to be nanoscopic.
      Type I mixtures are likely to be better models for biological membranes.

PMID- 18805393
TI  - Lipid lateral diffusion and membrane heterogeneity.
AB  - The pulsed field gradient (pfg)-NMR method for measurements of translational
      diffusion of molecules in macroscopically aligned lipid bilayers is described.
      This technique is proposed to have an appreciable potential for investigations in
      the field of lipid and membrane biology. Transport of molecules in the plane of
      the bilayer can be successfully studied, as well as lateral phase separation of
      lipids and their dynamics within the bilayer organizations. Lateral diffusion
      coefficients depend on lipid packing and acyl chain ordering and investigations
      of order parameters of perdeuterated acyl chains, using (2)H NMR quadrupole
      splittings, are useful complements. In this review we summarize some of our
      recent achievements obtained on lipid membranes. In particular, bilayers
      exhibiting two-phase coexistence of liquid disordered (l(d)) and liquid ordered
      (l(o)) phases are considered in detail. Methods for obtaining good oriented lipid
      bilayers, necessary for the pfg-NMR method to be efficiently used, are also
      briefly described. Among our major results, besides determinations of l(d) and
      l(o) phases, belongs the finding that the lateral diffusion is the same for all
      components, independent of the molecular structure (including cholesterol
      (CHOL)), if they reside in the same domain or phase in the membrane. Furthermore,
      quite unexpectedly CHOL seems to partition into the l(d)and l(o) phases to
      roughly the same extent, indicating that CHOL has no strong preference for any of
      these phases, i.e. CHOL seems to have similar interactions with all of the
      lipids. We propose that the lateral phase separation in bilayers containing one
      high-T(m) and one low-T(m) lipid together with CHOL is driven by the increasing
      difficulty of incorporating an unsaturated or prenyl lipid into the highly
      ordered bilayer formed by a saturated lipid and CHOL, i.e. the phase transition
      is entropy driven to keep the disorder of the hydrocarbon chains of the
      unsaturated lipid.

PMID- 18805394
TI  - Solution structure of peptide AG4 used to form silver nanoparticles.
AB  - The preparation of silver nanoparticles (AgNPs) is of great interest due to their
      various biological activities, such as observed in their antimicrobial and wound
      healing actions. Moreover, the formation of AgNPs using silver-binding peptide
      has certain advantages because they can be made in aqueous solution at ambient
      temperature. The solution structure of the silver-binding peptide AG4 was
      determined using nuclear magnetic resonance spectroscopy, and the site of the AG4
      interaction with AgNPs was elucidated.

PMID- 18805395
TI  - Immunomodulatory effect of resistin in human dendritic cells stimulated with
      lipoteichoic acid from Staphylococcus aureus.
AB  - Resistin is an adipokine whose physiologic role in obesity, type II diabetes
      mellitus, and inflammatory diseases has been a subject of debate because while it
      is expressed in adipocytes and adipose tissue in mouse, it is expressed in
      leukocytes, such as macrophages, in human. In the present study, we attempt to
      define the effect of resistin on human dendritic cells (DCs) derived from CD14(+)
      monocytes. When DCs were stimulated with lipoteichoic acid (LTA) and treated with
      various concentrations of resistin, antigen-uptake process and the endocytic
      capacity of DCs were decreased. It is intriguing that resistin attenuated
      cytokine production in LTA-primed DCs. Consequently, T cell activity was reduced
      when lymphocytes were mixed with Staphylococcus aureus-primed autologous DCs
      treated with resistin compared to S. aureus-primed DCs without resistin. Our
      results suggest that resistin interferes with the efficacy of immune responses
      activated by Gram-positive bacterial infection in human DCs.

PMID- 18805396
TI  - RNA interference mediated inhibition of Chikungunya virus replication in
      mammalian cells.
AB  - Chikungunya has emerged as one of the most important arboviral infection of
      public health significance. Recently several parts of Indian Ocean islands and
      India witnessed explosive, unprecedented epidemic. So far, there is no effective
      antiviral or licensed vaccine available against Chikungunya infection. RNA
      interference mediated inhibition of viral replication has emerged as a promising
      antiviral strategy. In this study, we examined the effectiveness of small
      interfering RNAs (siRNAs) against the inhibition of Chikungunya virus replication
      in Vero cells. Two siRNAs against the conserved regions of nsP3 and E1 genes of
      Chikungunya virus were designed. The siRNA activity was assessed by detecting
      both the infectious virus and its genome. The results indicated a reduction of
      virus titer up to 99.6% in siRNA transfected cells compared to control. The viral
      inhibition was most significant at 24h (99%), followed by 48 h (65%) post
      infection. These results were also supported by the quantitative RT-PCR assay
      revealing similar reduction in Chikungunya viral genomic RNA. The siRNAs used had
      no effect on the expression of house keeping gene indicating non-interference in
      cellular mechanism. The specific and marked reduction in viral replication
      against rapidly replicating Chikungunya virus achieved in this study offers a
      potential new therapeutic approach. This is the first report demonstrating the
      effectiveness of siRNA against in vitro replication of Chikungunya virus.

PMID- 18805397
TI  - Quantitative analysis of human tissue-specific differences in methylation.
AB  - Tissue-specific differentially methylated regions (tDMRs) have been identified
      and implicated for their indispensable involvement in mammalian development and
      tissue differentiation. In this report, a quantitative DNA methylation analysis
      was performed for 13 human orthologous regions of recently confirmed mouse tDMRs
      by using Sequenom Mass Array, by which bisulfite-treated fragments are
      quantitatively detected using time of flight mass spectroscopy analysis. Eight
      regions were shown as tDMRs in various tissues from three independent
      individuals. Testis DNA samples from eight individuals were also analyzed for
      methylation. Interestingly, there is evidence that the DNA methylation level is
      divergent among individuals. DNA methylation levels of five testis-specific DMRs
      were significantly inversely correlated with the number of spermatocytes.
      However, a positive correlation was seen at tDMRs located near the TRIM38 and
      CASZ1 genes. Our results indicate that tDMRs are conserved between mouse and
      human and may have an important role in regulating tissue function,
      differentiation, and aging.

PMID- 18805398
TI  - A simple assay for hyaluronidase activity using fluorescence polarization.
AB  - Hyaluronan is a large glycosaminoglycan and is a major constituent of the
      extracellular matrix, interacting with cell surface receptors such as CD44. We
      previously reported that fragmented hyaluronan, with the size frequently detected
      in cancer patients, induces CD44 cleavage and concomitantly enhances tumor cell
      migration. Although hyaluronan degradation to smaller fragments has been revealed
      to be a key reaction in regulating cancer progression, simple methods for
      continuously detecting hyaluronidase activity have not been established. Here, we
      show that fluorescently-labeled hyaluronan serves as a substrate for continuous
      assay of hyaluronidase activity. A very simple assay was established to measure
      degradation of hyaluronan based on fluorescence polarization. The developed assay
      method would provide a way for continuous measurement of cellular hyaluronidase
      activity and also for measurement of binding of hyaluronan to its receptors, and
      thus should be useful for investigation of the function of hyaluronan in cancer
      progression.

PMID- 18805399
TI  - Identification of the candidate genes regulated by RNA-directed DNA methylation
      in Arabidopsis.
AB  - RNA-directed DNA methylation (RdDM) is a process in which 24 nucleotide (nt)
      small interfering RNAs (siRNAs) guide de novo cytosine methylation in the
      homologous genomic DNA region. Of several factors involving 24 nt siRNA
      accumulation, RNA-dependent RNA polymerase 2 (RDR2) is a key component, because
      accumulation of 24 nt siRNA disappears in the Arabidopsis rdr2 mutant. Here, we
      compared expression profiles among wild-type, rdr2-1 and ddc (drm1drm2cmt3), DNA
      methyltransferase triple mutant, using a whole genome tiling array to identify
      the candidate genes directly downregulated by RdDM-related 24 nt siRNAs. Of the
      transcripts upregulated in the mutants, we searched for those whose coding
      regions or flanking regions have siRNA-generating loci. We found upregulated
      expression of 18 transcripts with AGI codes and 19 predicted transcriptional
      units (TUs) with siRNA loci in both rdr2-1 and ddc. Our study provided important
      information for understanding the relationship between RdDM and the identified
      candidate genes.

PMID- 18805400
TI  - Modelling and molecular dynamics of the interaction between the E3 ubiquitin
      ligase Itch and the E2 UbcH7.
AB  - Itch, a member of the E6AP carboxy terminus (HECT) domain-containing family of
      ubiquitin E3 ligases, acts in concert with the ubiquitin activating enzyme (E1)
      and the ubiquitin conjugating enzyme (E2) to catalyze ubiquitylation of protein
      targets. This sub-family of E3s shares a 350 residue C-terminal HECT domain
      having a strictly conserved catalytic Cys, and recruiting its cognate ubiquitin
      loaded E2. HECT domains possess intrinsic enzymatic activity, by accepting
      ubiquitin from an E2, forming a ubiquitin thiolester intermediate, and directly
      catalyzing ubiquitylation of the target protein. Several hypotheses have been
      proposed for the biochemical mechanism underlying the structural relationship of
      the HECT-E2 association and subsequent ubiquitin transfer. Nonetheless, a
      detailed characterization of the process is still missing. In this work, we have
      used molecular dynamic simulations, free energy calculations, protein modelling
      techniques and normal modes analysis to get a deeper characterization of the
      static and dynamical properties of this interaction mechanism. We hypothesize a
      correlated slow-frequency motion that involves two different hinge regions of the
      HECT domain. The identification of the amino acid residues responsible for the
      HECT-E2 interaction, and for the dynamical properties of the ubiquitin transfer
      process, may be of relevant interest for pharmacological and therapeutical
      purposes.

PMID- 18805401
TI  - Tumor necrosis factor alpha inhibits erythroid differentiation in human
      erythropoietin-dependent cells involving p38 MAPK pathway, GATA-1 and FOG-1
      downregulation and GATA-2 upregulation.
AB  - The proinflammatory cytokine tumor necrosis factor alpha (TNFalpha) has been
      linked to inflammation- and cancer-related anemia, which reduces both quality of
      life and prognosis of patients. The aim of this study was to reveal molecular
      mechanisms linked to the inhibition of erythroid differentiation by TNFalpha. In
      this study, we showed that the inhibition of erythropoietin (Epo)-mediated
      differentiation by TNFalpha lead to a downregulation of hemoglobin synthesis and
      was correlated to a modulation of key erythroid transcription factors. Thus, a
      reverse of the transcription factor GATA-1/GATA-2 balance normally present during
      erythropoiesis, as well as a downregulation of the cofactor of GATA-1, friend of
      GATA-1 (FOG-1), and the coregulating transcription factor nuclear factor
      erythroid 2 (NF-E2) was observed after TNFalpha treatment. Moreover, we showed a
      reduction of GATA-1/FOG-1 interaction due to a reduced transcription of GATA-1
      and a proteasome-dependent FOG-1 degradation after TNFalpha treatment. These
      changes led to an inhibition of erythroid gene expression including Epo receptor
      (EpoR), alpha- and gamma-globin, erythroid-associated factor (ERAF),
      hydroxymethylbilane synthetase (HMBS), and glycophorin A (GPA). An analysis of
      distinct signaling pathway activations then revealed an activation of p38 by TNF,
      as well as a corresponding involvement of this mitogen-activated protein kinase
      (MAPK) in the cytokine-dependent inhibition of erythroid differentiation. Indeed
      the p38 inhibitor, SB203580, abrogated the inhibitory effect of TNFalpha on the
      major erythroid transcription factor GATA-1 as well as erythroid marker
      expression in Epo-induced TF-1 cells. Overall, these data contribute to a better
      understanding of cytokine-dependent anemia, by giving first hints about key
      erythroid transcription factor modulations after TNFalpha treatment as well as an
      involvement of p38 in the inhibition of erythroid differentiation.

PMID- 18805402
TI  - Phosphodiesterases link the aryl hydrocarbon receptor complex to cyclic
      nucleotide signaling.
AB  - The aryl hydrocarbon receptor (AHR) is a major transcription factor regulated by
      different mechanisms. The classical view of AHR activation by xenobiotics needs
      to be amended by recent findings on the regulation of AHR by endogenous ligands
      and by crosstalk with other signaling pathways. In the cytosol the AHR recruits a
      large number of binding partners, including HSP90, p23, XAP2 and the ubiquitin
      ligases cullin 4B and CHIP. Furthermore, XAP2 binds the cyclic nucleotide
      phosphodiesterases PDE2A and PDE4A5. PDE2A inhibits nuclear translocation of AHR
      suggesting an important regulatory role of cyclic nucleotides in AHR trafficking.
      Signaling involving cAMP is organized in subcellular compartments and a distinct
      cAMP compartment might be required for proper AHR mobility and function. We
      conclude that the AHR complex integrates ligand binding and cyclic nucleotide
      signaling to generate an adequate transcriptional response.

PMID- 18805403
TI  - Measures of striatal insulin resistance in a 6-hydroxydopamine model of
      Parkinson's disease.
AB  - Clinical evidence has shown a correlation between Parkinson's disease (PD) and
      Type 2 Diabetes (T2D), as abnormal glucose tolerance has been reported in >50% of
      PD patients. The development of insulin resistance and the degeneration of
      nigrostriatal dopamine (DA) neurons are both mediated by oxidative mechanisms,
      and oxidative stress is likely a mechanistic link between these pathologies.
      Although glucose uptake in neuronal tissues is primarily non-insulin dependent,
      proteins involved in insulin signaling, such as insulin receptor substrate 2
      (IRS2) and glucose transporter 4 (GLUT4), are present in the basal ganglia. The
      purpose of this study was to determine whether nigrostriatal DA depletion affects
      measures of insulin resistance in the striatum. Six weeks after 6-hydroxydopamine
      (6-OHDA) infusion into the medial forebrain bundle, rats were classified as
      having either partial (20-65%) or severe (90-99%) striatal DA depletion.
      Increased IRS2 serine phosphorylation, a marker of insulin resistance, was
      observed in the DA-depleted striatum. Additionally, severe depletion resulted in
      decreased total IRS2, indicating possible degradation of the protein. Decreased
      phosphorylation of AKT and expression of the kinase glycogen synthase kinase-3
      alpha (GSK3-alpha) was also measured in the striatum of severely DA-depleted
      animals. Finally, expression of heat shock protein 25 (Hsp25), which is
      protective against oxidative damage and can decrease stress kinase activity, was
      decreased in the striatum of lesioned rats. Together, these results support the
      hypothesis that nigrostriatal DA depletion impairs insulin signaling in the basal
      ganglia.

PMID- 18805404
TI  - A naloxonazine sensitive (mu1 receptor) mechanism in the parabrachial nucleus
      modulates eating.
AB  - The parabrachial nucleus (PBN) is an area of the brain stem that controls eating
      and contains endogenous opioids and their receptors. Previously, we demonstrated
      that acute activation of mu opioid receptors (MOPR) in the lateral PBN increased
      food consumption. MOPRs have been divided operationally into mu(1) and mu(2)
      receptor subtypes on the basis of the ability of naloxonazine (Nlxz) to block the
      former but not the latter. We used autoradiography to measure whether Nlxz blocks
      stimulation by the mu(1)/mu(2) agonist DAMGO (D-Ala2, N-Me-Phe4, Gly5-ol
      enkephalin) of the incorporation of [(35)S]-guanosine 5'(gamma-thio)triphosphate
      ([(35)S]-GTPgammaS) into sections of the PBN. In vitro, Nlxz dose dependently
      inhibited receptor coupling in all areas of the PBN. The 1 muM concentration of
      Nlxz reduced stimulation by 93.1+/-5% in the lateral inferior PBN (LPBNi) and by
      90.5+/-4% in the medial parabrachial subregion (MPBN). Administration of Nlxz
      directly into the LPBNi decreased both food intake and agonist stimulated
      coupling, ex vivo, for the 24-h period after infusion. Infusion of Nlxz into the
      intended area reduced food intake by 42.3% below baseline values. Nlxz infusion
      prevented DAMGO stimulation of G-protein coupling in LPBNi and markedly reduced
      this stimulation in the MPBN. The incomplete inhibition of DAMGO-stimulated
      coupling in the MPBN is most likely due to the limited diffusion of Nlxz from the
      site of infusion (LPBNi) into this brain region. In conclusion, this study
      demonstrates that the mu(1) opioid receptor subtype is present in the
      parabrachial nucleus of the pons and that these receptors serve to modulate
      feeding in rats.

PMID- 18805405
TI  - PXR-mediated transcriptional activation of CYP3A4 by cryptotanshinone and
      tanshinone IIA.
AB  - Danshen (Radix Salvia miltiorrhiza) is a famous Traditional Chinese Medicine used
      widely for the treatment of coronary heart disease and cerebrovascular disease.
      Diterpenoid tanshinones including tanshinone I, tanshinone IIA and
      cryptotanshinone are the major bioactive components from Danshen herb. Previous
      reports have demonstrated that Danshen extracts could induce the expression of
      CYP3A in rodents, however, the constituents responsible for Danshen-mediated
      CYP3A induction and the underlying molecular mechanisms remain unknown. The
      discovery of a family of nuclear receptors such as pregnane X receptor (PXR),
      constitutive androstane receptor (CAR) and glucocorticoid receptor (GR) gives
      insight into the molecular explanation of CYP3A induction by xenobiotics. In the
      present study, interactions between Danshen constituents and human PXR were
      evaluated using a reporter gene assay. Our observations showed that Danshen
      ethanol extract could activate human PXR and induce the CYP3A4 reporter construct
      in HepG2 cells. Tanshinone IIA and cryptotanshinone were identified as
      efficacious PXR agonists, and cryptotanshinone activated the CYP3A4 promoter more
      strongly than tanshinone IIA. Furthermore, CAR and GR were also involved in the
      induction of CYP3A4 expression by tanshinones, though their roles seemed not as
      important as PXR. Treatment of LS174T cells with cryptotanshinone or tanshinone
      IIA resulted in a significant increase of CYP3A4 mRNA, which was consistent with
      the results from the reporter gene assay. Collectively, activation of PXR and the
      resultant CYP3A4 induction mediated by cryptotanshinone and tanshinone IIA
      provide a molecular mechanism for previously observed CYP3A induction by Danshen
      extracts, and our findings also suggest that caution should be taken when Danshen
      products are used in combination with therapeutic drugs metabolized by CYP3A4.

PMID- 18805406
TI  - Panaxydol treatment enhances the biological properties of Schwann cells in vitro.
AB  - Schwann cells (SCs), the glial cells of the peripheral nerve system, play a key
      role in the regeneration of injured peripheral nerves. However, problems with the
      use of SCs to repair peripheral nerves include attenuated biologic properties and
      impaired function with ageing. Panaxydol (PND) effectively protects neurons
      against injury in degenerative diseases. We investigated the protective role of
      PND in SCs through immunocytochemistry and ELISA assay. PND promoted the
      expression and secretion of nerve growth factor (NGF) and brain-derived
      neurotrophic factor (BDNF) by SCs in a dose-dependent manner at doses of 2.5-20
      and 5.0-20 microM, respectively. The effects on both factors were maximal at 10
      microM. PND also enhanced the synthesis of actin, a key component of the
      cytoskeleton. When we examined mitochondria in SCs with probes marked with
      rhodamine-123, fluorescence intensity was stronger in the PND group than in a
      control group, indicating a stabilized mitochondrial transmembrane potential. PND
      modified cytoskeleton dynamics and induced SCs to secrete and express
      neurotrophic factors (NTFs), and to resist high energy consumption in a dose
      dependent manner. It exerted its maximum effect at 10 microM. PND treatment of
      SCs might be promising strategies for the application of these cells in repairing
      PNS injury by enhancing the biological properties.

PMID- 18805407
TI  - Analytical study of three cystatin C assays and their impact on cystatin C-based
      GFR-prediction equations.
AB  - BACKGROUND: Cystatin C-based equations are used to estimate GFR. However, three
      cystatin C immunoassays are on the market. Difference in cystatin C assays could
      have strong consequences on the accuracy and precision of cystatin C-based
      equations. We have performed an analytical study of these three assays and
      studied potential differences between assays on the precision of cystatin C-based
      equations. METHODS: We have studied imprecision, recovery, linearity and
      interferences of the three immunoassays (nephelometric assay from Siemens and
      turbidimetric assays from Dako and Gentian). The impact of differences in
      cystatin C assays has been studied for the equations published by Levey (Siemens
      assay) and Grubb (Dako assay). RESULTS: Analytical performance of the Dako assay
      is slightly less high. For cystatin C values below 2.5 mg/L, no statistical
      difference is found between results given by the Dako and the Gentian assays. So,
      both assays can be used in the Grubb equation. Cystatin C results are different
      with the Siemens assay. The Levey equation, built with the Siemens assay, can
      only be used with cystatin C values measured with this assay. Using the Dako or
      Gentian assay results in the Levey equation can lead to differences in estimating
      GFR up to 6 mL/min/1.73 m2. Differences can reach 9.5 mL/min/1.73 m2 if the
      Siemens assay is used in the Grubb equation. CONCLUSION: The Siemens and Gentian
      assays seem analytically more valid than the Dako assay for cystatin C
      determination. Differences in cystatin C assays can lead to significant
      differences in cystatin C-based equations. However, these differences seem less
      important than the differences observed with creatinine and creatinine-based
      equations.

PMID- 18805408
TI  - Curve fitting approach for measurement of cellular osmotic properties by the
      electrical sensing zone method. I. Osmotically inactive volume.
AB  - We have investigated the confounding effects of dynamic range limitations on
      measurement of the osmotically inactive volume using electrical sensing zone
      instruments (e.g., Coulter counters), and propose an improved approach to
      parameter estimation. The conventional approach for analysis of cell size
      distributions measured by such particle sizing instruments requires data
      truncation: the mean cell volume is computed after exclusion of data below a
      specified lower bound (typically chosen to remove artifacts due to small-volume
      noise) and above an upper bound (typically governed by instrument limitations).
      The osmotically inactive volume is then estimated from a Boyle-van't Hoff plot of
      the averaged volume data obtained after exposure to various solution
      osmolalities. We demonstrate that systematic exclusion of data in the
      conventional approach introduces bias that results in erroneously high estimates
      of the osmotically inactive volume fraction. To minimize this source of error, we
      have devised a new algorithm based on fitting a bimodal distribution model to the
      non-truncated volume data. In experiments with mouse insulinoma (MIN6) cells, the
      osmotically inactive volume fraction was estimated to be 0.15+/-0.01 using the
      new method, which was significantly smaller than the estimate of 0.37+/-0.02
      obtained using the conventional method (p<0.05). In silico experiments indicated
      that the parameter estimate obtained by the new method was accurate within 5%,
      whereas the error associated with the conventional approach was approximately
      150%. Parametric analysis was used to elucidate the sensitivity of errors to
      variations in instrument dynamic range and cell volume distribution width.

PMID- 18805409
TI  - The effect of cryoprotectant on kangaroo sperm ultrastructure and mitochondrial
      function.
AB  - This study examined the effect of cryoprotectants (20% DMSO, a 10% DMSO/10%
      glycerol mixture, 20% glycerol and 1M sucrose solution) on kangaroo sperm
      structure and function, along with the effect of varying concentrations of
      glycerol on sperm mitochondrial function. Eastern grey kangaroo cauda
      epididymidal spermatozoa were incubated for 10 min at 35 degrees C in each
      cryoprotectant and the plasma membrane integrity (PMI) and motility assessed
      using light microscopy. The same samples were fixed for TEM and the
      ultrastructural integrity of the spermatozoa examined. To investigate the effect
      of glycerol on the kangaroo sperm mitochondrial function, epididymidal
      spermatozoa were incubated with JC-1 in Tris-citrate media at 35 degrees C for 20
      min in a range of glycerol concentrations (0%, 5%, 10%, 15% and 20%) and the
      mitochondrial membrane potential (MMP) and plasma membrane integrity determined.
      As expected, incubation of spermatozoa in 20% glycerol for 10 min resulted in a
      significant reduction in motility, PMI and ultrastructural integrity.
      Interestingly, incubation in 20% DMSO resulted in no significant reduction in
      motility or PMI but a significant loss of structural integrity when compared to
      the control spermatozoa (0% cryoprotectant). However, 20% DMSO was overall less
      damaging to sperm ultrastructure than glycerol, a combination of 10% glycerol and
      10% DMSO, and sucrose. While all glycerol concentrations had an adverse effect on
      mitochondrial function, the statistical models presented for the relationship
      between MMP and glycerol predicted that spermatozoa, when added to 20% glycerol,
      would lose half of their initial MMP immediately at 35 degrees C and MMP would
      halve after 19.4 min at 4 degrees C. Models for the relationship between PMI and
      glycerol predicted that spermatozoa would lose half of their initial PMI after
      1.8 min at 35 degrees C and PMI would halve after 21.1 min at 4 degrees C. These
      results suggest that if glycerol is to be used as a cryoprotectant for kangaroo
      spermatozoa then it is best administered at 4 degrees C and that mitochondrial
      function is more sensitive to glycerol than PMI. Future research should be
      directed at investigating strategies that reduce exposure of spermatozoa to
      glycerol during processing and that test the cryoprotective properties of 20%
      DMSO for kangaroo spermatozoa.

PMID- 18805410
TI  - Tissue-specific functions of the Caenorhabditis elegans p120 Ras GTPase
      activating protein GAP-3.
AB  - All metazoan genomes encode multiple RAS GTPase activating proteins (RasGAPs)
      that negatively regulate the conserved RAS/MAPK signaling pathway. In mammals,
      several RasGAPs exhibit tumor suppressor activity by preventing excess RAS signal
      transduction. We have identified gap-3 as the to date missing
      Caenorhabditiselegans member of the p120 RasGAP family. By studying the genetic
      interaction of gap-3 with the two previously identified RasGAPs gap-1 and gap-2,
      we find that different combinations of RasGAPs are used to repress LET-60 RAS
      signaling depending on the cellular context. GAP-3 is the predominant negative
      regulator of RAS during meiotic progression of the germ cells, while GAP-1 is the
      key inhibitor of RAS during vulval induction. In other tissues such as the sex
      myoblasts or the chemosensory neurons, all three RasGAPs act in concert. The C.
      elegans RasGAPs have thus undergone partial specialization after gene duplication
      to allow the differential regulation of the RAS/MAPK signaling pathway in
      different cell types. A similar tissue specialization of the human tumor
      suppressor genes may explain the strong bias in the type of cancer they promote
      when mutated.

PMID- 18805411
TI  - Dynamic regulation of retinoic acid-binding proteins in developing, adult and
      neoplastic skin reveals roles for beta-catenin and Notch signalling.
AB  - Retinoic acid (RA) signalling is essential for epidermal differentiation;
      however, the mechanisms by which it acts are largely unexplored. Partitioning of
      RA between different nuclear receptors is regulated by RA-binding proteins. We
      show that cellular RA-binding proteins CRABP1 and CRABP2 and the fatty acid
      binding protein FABP5 are dynamically expressed during skin development and in
      adult tissue. CRABP1 is expressed in embryonic dermis and in the stroma of skin
      tumours, but confined to the hair follicle dermal papilla in normal postnatal
      skin. CRABP2 and FABP5 are expressed in the differentiating cells of sebaceous
      gland, interfollicular epidermis and hair follicles, with FABP5 being a prominent
      marker of sebaceous glands and anagen follicle bulbs. All three proteins are
      upregulated in response to RA treatment or Notch activation and are negatively
      regulated by Wnt/beta-catenin signalling. Ectopic follicles induced by beta
      catenin arise from areas of the sebaceous gland that have lost CRABP2 and FABP5;
      conversely, inhibition of hair follicle formation by N-terminally truncated Lef1
      results in upregulation of CRABP2 and FABP5. Our findings demonstrate that there
      is dynamic regulation of RA signalling in different regions of the skin and
      provide evidence for interactions between the RA, beta-catenin and Notch
      pathways.

PMID- 18805412
TI  - Perivascular cells increase expression of ciliary neurotrophic factor following
      partial denervation of the rat neurohypophysis.
AB  - The expression of ciliary neurotrophic factor (CNTF) was investigated
      immunocytochemically during the axonal degeneration and collateral axonal
      sprouting response that follows partial denervation of the rat neurohypophysis. A
      significant increase in the number of CNTF-immunoreactive (CNTF-ir) cells was
      observed in the neurohypophysis of partially denervated animals compared to age
      matched sham-operated controls by 5 days post-denervation, remaining elevated
      throughout the 30 day post-denervation period. Stereometric assessment of the
      numbers of CNTF-ir cells within the partially denervated neurohypophysis
      demonstrated a 36% increase by 3 days following denervation reaching 130% of
      control values by 10 days post-lesion. The cell numbers remained elevated
      throughout the 30 day post-lesion period suggesting that CNTF may play a role in
      the neurosecretory axonal sprouting process known to occur between 10 and 30 days
      post-denervation. Subsequent preparations pairing anti-CNTF with antibodies
      against ED1, CR3, p75 low affinity neurotrophin receptor (p75(LNGFR)), and
      S100beta, demonstrated that CNTF was exclusively localized in a phenotypically
      distinct population of perivascular cells. The association of perivascular cells
      with phagocytic activity was confirmed by dual-label fluorescence microscopy
      showing the colocalization of P75(LNGFR)-ir and OX-42-ir in cells expressing the
      ED-1 antigen. No increase in CNTF-ir was observed in non-injured animals in which
      heightened levels of neurosecretory activity were induced physiologically. These
      results suggest that increased CNTF-ir occurs in response to conditions which
      induce high levels of phagocytic activity by perivascular cells in the axotomized
      neurohypophysis which is sustained throughout a period in which axonal sprouting
      is known to occur in the partially denervated neurohypophysis.

PMID- 18805413
TI  - Opisthorchis viverrini: detection by polymerase chain reaction (PCR) in human
      stool samples.
AB  - A polymerase chain reaction (PCR) assay was evaluated for detection of
      Opisthorchis viverrini eggs in the stool specimens of light and heavily infected
      individuals in Khon Kaen province of Thailand. A total of 75 fecal specimens were
      analyzed by PCR following DNA extraction. All the microscopically positive
      samples were positive by PCR, while 23 of 30 (76.6%) microscopically negative
      samples were also PCR positive. The sensitivity of the assay was 5 eggs/g of
      stool. This method is potentially useful in the diagnosis of human
      opisthorchiasis in endemic areas for treatment and in epidemiological
      investigations.

PMID- 18805414
TI  - Enhanced glycolysis induced by mtDNA mutations does not regulate metastasis.
AB  - We addressed the issue of whether enhanced glycolysis caused by mtDNA mutations
      independently induces metastasis in tumor cells using mtDNA transfer technology.
      The resultant trans-mitochondrial cybrids sharing the same nuclear background of
      poorly metastatic carcinoma P29 cells, P29mtA11 and P29mtDelta cybrids, possessed
      mtDNA with a G13997A mutation from highly metastatic carcinoma A11 cells and
      mtDNA with a 4696bp deletion mutation, respectively. The P29mtDelta cybrids
      expressed enhanced glycolysis, but did not express ROS overproduction and high
      metastatic potential, whereas P29mtA11 cybrids showed enhanced glycolysis, ROS
      overproduction, and high metastatic potential. Thus, enhanced glycolysis alone
      does not induce metastasis in the cybrids.

PMID- 18805415
TI  - Specific reaction of alpha,beta-unsaturated carbonyl compounds such as 6-shogaol
      with sulfhydryl groups in tubulin leading to microtubule damage.
AB  - 6-Shogaol and 6-gingerol are ginger components with similar chemical structures.
      However, while 6-shogaol damages microtubules, 6-gingerol does not. We have
      investigated the molecular mechanism of 6-shogaol-induced microtubule damage and
      found that the action of 6-shogaol results from the structure of alpha,beta
      unsaturated carbonyl compounds. alpha,beta-Unsaturated carbonyl compounds such as
      6-shogaol react with sulfhydryl groups of cysteine residues in tubulin, and
      impair tubulin polymerization. The reaction with sulfhydryl groups depends on the
      chain length of alpha,beta-unsaturated carbonyl compounds. In addition,
      alpha,beta-unsaturated carbonyl compounds are more reactive with sulfhydryl
      groups in tubulin than in 2-mercaptoethanol, dithiothreitol, glutathione and
      papain, a cysteine protease.

PMID- 18805416
TI  - The promiscuity of ARF interactions with the proteasome.
AB  - The tumor suppressor ARF is one of the most important oncogenic stress sensors in
      mammalian cells. Its effect is exerted through the interaction with different
      cellular partners, often resulting in their functional inactivation. This review
      focuses on the role played by the proteasome in ARF regulation of protein
      turnover and the function of most of its interacting partners. Specific
      proteasome components appear to be involved in the regulation of ARF turnover,
      bringing to light a complex network of interactions between ARF and the
      proteasome.

PMID- 18805417
TI  - In HspA from Helicobacter pylori vicinal disulfide bridges are a key determinant
      of domain B structure.
AB  - Helicobacter pylori produces a heat shock protein A (HspA) that is unique to this
      bacteria. While the first 91 residues (domain A) of the protein are similar to
      GroES, the last 26 (domain B) are unique to HspA. Domain B contains eight
      histidines and four cysteines and was suggested to bind nickel. We have produced
      HspA and two mutants: Cys94Ala and Cys94Ala/Cys111Ala and identified the
      disulfide bridge pattern of the protein. We found that the cysteines are engaged
      in three disulfide bonds: Cys51/Cys53, Cys94/Cys111 and Cys95/Cys112 that result
      in a unique closed loop structure for the domain B.

PMID- 18805418
TI  - In vitro perturbation of aggregation processes in beta-amyloid peptides: a
      spectroscopic study.
AB  - We have performed an in vitro study to investigate the molecular basis of the
      aggregation kinetic of 1-40 beta-amyloid peptides (Abeta and the possibility of
      affecting this aggregation process using an exogenous natural polycyclic pigment,
      hypericin (Hyp). The effect of Hyp on the self-assembly process at different
      times of the aggregation kinetic has been investigated utilizing a chaperon-like
      molecule, alpha-crystallin. Circular dichroism and fluorescence results suggest
      that Hyp can associate to precursors of the mature fibrils and perturb the
      aggregation process through intermolecular interactions with the Abeta peptides.

PMID- 18805419
TI  - Molecular cloning and gene expression of Foxl2 in the frog Rana rugosa.
AB  - Foxl2 is a transcription factor that plays a crucial role in the regulation of
      the early development of the female gonad in mammals and fish. However, little is
      known regarding its role in ovarian differentiation in amphibians. In this study,
      we isolated a Foxl2 cDNA from the ovary of the frog Rana rugosa and Xenopuslaevis
      and examined its expression during gonadal sex differentiation in R. rugosa.
      Alignment of known Foxl2 sequences from vertebrates showed high identity of the
      Foxl2 open reading frame and protein sequences, in particular the forkhead domain
      and C-terminal region, with other vertebrate sequences. Among different adult
      tissues, Foxl2 was expressed at its highest level in the ovary. Real-time RT-PCR
      analysis showed that Foxl2 expression was sexually dimorphic during gonadal sex
      differentiation in R. rugosa. In addition, Foxl2, which was detected
      immunochemically in somatic cells surrounding oocytes in the ovary, promoted R.
      rugosaCYP19 transcription in luciferase promoter assays conducted in A6 cells. We
      also found by FISH analysis that Foxl2 was an autosomal gene. Altogether, these
      results suggest that Foxl2 probably plays a very important role in ovarian
      differentiation of R. rugosa by possibly regulating CYP19 expression. The factor
      that up-regulates Foxl2 expression in female gonads still remains to be
      identified.

PMID- 18805420
TI  - Molecular cloning, tissue distribution and expression profiles of thyroid hormone
      receptors during embryogenesis in orange-spotted grouper (Epinephelus coioides).
AB  - Three distinct thyroid hormone receptor (TR) cDNAs (gTRalphaA, gTRalphaB and
      gTRbeta) were cloned and sequenced in orange-spotted grouper (Epinephelus
      coioides). The cDNA of gTRalphaA consisted of 1555-bp and encoded a putative
      protein of 416 amino acids, while the cDNA of gTRalphaB consisted of 1459-bp and
      encoded 398 amino acids. The cDNA of gTRbeta is 1470-bp in length and encoded 395
      amino acids. The cDNAs of gTRalphaA and gTRalphaB had 68.7% identity in
      nucleotide sequence and 83.9% identity in deduced amino acid sequence, and shared
      57.8%, 57.9% identity in nucleotide sequence and 76.5%, 76.6% in deduced amino
      acid sequence with gTRbeta, respectively. mRNA expression of gTR was determined
      by using real-time RT-PCR. The zygotic mRNA expression of gTRalphaA, gTRalphaB
      and gTRbeta was already presented at the blastula stage, and decreased by
      gastrulation and body segment appearance. Both gTRalphaA and gTRbeta mRNAs
      dramatically increased by brain vesicle appearance and lens formation stages,
      whereas the magnitude of the increase of gTRbeta was higher than that of
      gTRalphaA. However, gTRalphaB remained relatively constant. All three gTR mRNAs
      were detected in various tissues of adult fish, with considerable levels found in
      the pituitary and brain. The expression of gTRalphaA and gTRalphaB was
      ubiquitous, while the gTRbeta transcription in the pituitary was higher than
      other tissues. The results suggest that gTRs may be important in adult grouper
      brain function and that gTRalphaA and gTRalphaB may be important factors in
      metabolic regulation. In addition, gTRbeta may be the major TR isoform in the
      regulation of TSH activity by TH feedback in grouper.

PMID- 18805421
TI  - Selective activation of estrogen receptor alpha in Japanese quail embryos affects
      reproductive organ differentiation but not the male sexual behavior or the
      parvocellular vasotocin system.
AB  - Estradiol is crucial for normal female differentiation in birds. Developmental
      effects of estrogen are believed to be mediated by slow genomic actions through
      the nuclear estrogen receptors alpha (ERalpha) and/or beta (ERbeta).
      Consequently, exogenous compounds that interfere with the ERs may disrupt sexual
      differentiation of the reproductive organs and of the brain areas controlling
      sexual behaviors. The present study was conducted to elucidate the role of
      ERalpha in xenoestrogen-induced disruption of sexual differentiation in the
      Japanese quail (Coturnix japonica). Embryonic treatment with the synthetic
      estrogen, ethinylestradiol (EE(2)), and with the ERalpha-selective agonist,
      propyl pyrazole triol (PPT), induced oviductal malformations in females and
      retention of oviducts in males. Both EE(2) and PPT caused weight asymmetry
      between left and right testes and reduced the cloacal gland area in males. EE(2)
      significantly reduced the copulatory behavior in males whereas PPT had no effect
      on this behavior. The sexually dimorphic parvocellular vasotocin-immunoreactive
      (VT-ir) system in the medial preoptic nucleus (POM), the lateral septum (SL) and
      the medial part of the nucleus of the stria terminalis (BSTm), was not affected
      by EE(2) or PPT. Our results suggest that xenoestrogen-induced effects on
      reproductive organ differentiation are mediated by ERalpha, whereas
      demasculinization of male copulatory behavior and the VT-ir system appears not to
      be induced by activation of ERalpha alone.

PMID- 18805422
TI  - Hepatopancreas alteration of the blue crab Callinectes sapidus by the
      rhizocephalan barnacle Loxothylacus texanus.
AB  - A histological study of the hepatopancreas of the blue crab Callinectes sapidus
      parasitized by the rhizocephalan barnacle Loxothylacus texanus was conducted to
      explore if the degree of development of the parasite's rootlet system was
      correlated to its maturation process as seen by external characters of its
      reproductive body or externa. Four types of crabs were examined: control, with
      virgin and mature externa, and scarred. A clear progression with an increase in
      number and size of the parasite's rootlets in the hosts' hepatopancreas can be
      seen. Although the hepatopancreatic tubules remain functional, the hepatopancreas
      appears as a loose structure, completely infiltrated with L. texanus rootlets, in
      advanced stages of the parasitism.

PMID- 18805423
TI  - Marked differences between atrial and ventricular gene-expression remodeling in
      dogs with experimental heart failure.
AB  - Congestive heart failure (CHF) causes arrhythmogenic, structural and contractile
      remodeling, with important atrial-ventricular differences: atria show faster and
      greater inflammation, cell-death and fibrosis. The present study assessed time
      dependent left atrial (LA) and ventricular (LV) gene-expression changes in CHF.
      Groups of dogs were submitted to ventricular tachypacing (VTP, 240 bpm) for 24 h
      or 2 weeks, and compared to sham-instrumented animals. RNA from isolated LA and
      LV cardiomyocytes of each dog was analyzed by canine-specific microarrays
      (>21,700 probe-sets). LA showed dramatic gene-expression changes, with 4785
      transcripts significantly-altered (Q<5) at 24-hour and 6284 at 2-week VTP. LV
      gene-changes were more limited, with 52 significantly-altered at 24-hour and 130
      at 2-week VTP. Particularly marked differences were seen in ECM genes, with 153
      changed in LA (e.g. approximately 65-fold increase in collagen-1) at 2-week VTP
      versus 2 in LV; DNA/RNA genes (LA=358, LV=7); protein biosynthesis (LA=327,
      LV=14); membrane transport (LA=230, LV=8); cell structure and mobility (LA=159,
      LV=6) and coagulation/inflammation (LA=147, LV=1). Noteworthy changes in LV were
      genes involved in metabolism (35 genes; creatine-kinase B increased 8-fold at 2
      week VTP) and Ca(2+)-signalling. LA versus LV differential gene-expression
      decreased over time: 1567 genes were differentially expressed (Q<1) at baseline,
      1499 at 24-hour and 897 at 2-week VTP. Pathway analysis revealed particularly
      important changes in LA for mitogen-activated protein-kinase, apoptotic, and
      ubiquitin/proteasome systems, and LV for Krebs cycle and electron-transfer
      complex I/II genes. VTP-induced CHF causes dramatically more gene-expression
      changes in LA than LV, dynamically altering the LA-LV differential gene
      expression pattern. These results are relevant to understanding chamber-specific
      remodeling in CHF.

PMID- 18805424
TI  - The crystal structure of enamidase: a bifunctional enzyme of the nicotinate
      catabolism.
AB  - The hydrolysis of 1,4,5,6-tetrahydro-6-oxonicotinate to 2-formylglutarate is a
      central step in the catabolism of nicotinate in several Clostridia and
      Proteobacteria. This reaction is catalyzed by the novel enzyme enamidase, a new
      member of the amidohydrolase superfamily as indicated by its unique reaction,
      sequence relationship, and the stoichiometric binding of iron and zinc. A
      hallmark of enamidase is its capability to catalyze a two-step reaction: the
      initial decyclization of 1,4,5,6-tetrahydro-6-oxonicotinate leading to 2
      (enamine)glutarate followed by an additional hydrolysis step yielding (S)-2
      formylglutarate. Here, we present the crystal structure of enamidase from
      Eubacterium barkeri at 1.9 A resolution, providing a structural basis for
      catalysis and suggesting a mechanism for its exceptional activity and
      enantioselectivity. The enzyme forms a 222-symmetric tetramer built up by a dimer
      of dimers. Each enamidase monomer consists of a composite beta-sandwich domain
      and an (alpha/beta)(8)-TIM-barrel domain harboring the active site. With its
      catalytic binuclear metal center comprising both zinc and iron ions, enamidase
      represents a special case of subtype II amidohydrolases.

PMID- 18805425
TI  - Single-molecule fluorescence resonance energy transfer assays reveal
      heterogeneous folding ensembles in a simple RNA stem-loop.
AB  - We have examined the folding ensembles present in solution for a series of RNA
      oligonucleotides that encompass the replicase translational operator stem-loop of
      the RNA bacteriophage MS2. Single-molecule (SM) fluorescence assays suggest that
      these RNAs exist in solution as ensembles of differentially base-paired/base
      stacked states at equilibrium. There are two distinct ensembles for the wild-type
      sequence, implying the existence of a significant free energy barrier between
      "folded" and "unfolded" ensembles. Experiments with sequence variants are
      consistent with an unfolding mechanism in which interruptions to base-paired
      duplexes, in this example by the single-stranded loop and a single-base bulge in
      the base-paired stem, as well as the free ends, act as nucleation points for
      unfolding. The switch between folded and unfolded ensembles is consistent with a
      transition that occurs when all base-pairing and/or base-stacking interactions
      that would orientate the legs of the RNA stem are broken. Strikingly, a U-to-C
      replacement of a residue in the loop, which creates a high-affinity form of the
      operator for coat protein binding, results in dramatically different (un)folding
      behaviour, revealing distinct subpopulations that are either stabilised or
      destabilised with respect to the wild-type sequence. This result suggests
      additional reasons for selection against the C-variant stem-loop in vivo and
      provides an explanation for the increased affinity.

PMID- 18805426
TI  - A single mutation in the IF3 N-terminal domain perturbs the fidelity of
      translation initiation at three levels.
AB  - Bacterial translation initiation factor 3 (IF3) is involved in the fidelity of
      translation initiation at several levels, including start-codon discrimination,
      mRNA translation, and initiator-tRNA selection. The IF3 C-terminal domain (CTD)
      is required for binding to the 30S ribosomal subunit. N-terminal domain (NTD)
      function is less certain, but likely contributes to initiation fidelity. Point
      mutations in either domain can decrease initiation fidelity, but C-terminal
      domain mutations may be indirect. Here, the Y75N substitution mutation in the NTD
      is examined in vitro and in vivo. IF3(Y75N) protein binds 30S subunits normally,
      but is defective in start-codon discrimination, inhibition of initiation on
      leaderless mRNA, and initiator-tRNA selection, thereby establishing a direct role
      for the IF3 NTD in these initiation processes. A model illustrating how IF3
      modulates an inherent function of the 30S subunit is discussed.

PMID- 18805427
TI  - Sleep deprivation in a quantitative physiologically based model of the ascending
      arousal system.
AB  - A physiologically based quantitative model of the human ascending arousal system
      is used to study sleep deprivation after being calibrated on a small set of
      experimentally based criteria. The model includes the sleep-wake switch of mutual
      inhibition between nuclei which use monoaminergic neuromodulators, and the
      ventrolateral preoptic area. The system is driven by the circadian rhythm and
      sleep homeostasis. We use a small number of experimentally derived criteria to
      calibrate the model for sleep deprivation, then investigate model predictions for
      other experiments, demonstrating the scope of application. Calibration gives an
      improved parameter set, in which the form of the homeostatic drive is better
      constrained, and its weighting relative to the circadian drive is increased.
      Within the newly constrained parameter ranges, the model predicts repayment of
      sleep debt consistent with experiment in both quantity and distribution,
      asymptoting to a maximum repayment for very long deprivations. Recovery is found
      to depend on circadian phase, and the model predicts that it is most efficient to
      recover during normal sleeping phases of the circadian cycle, in terms of the
      amount of recovery sleep required. The form of the homeostatic drive suggests
      that periods of wake during recovery from sleep deprivation are phases of
      relative recovery, in the sense that the homeostatic drive continues to converge
      toward baseline levels. This undermines the concept of sleep debt, and is in
      agreement with experimentally restricted recovery protocols. Finally, we compare
      our model to the two-process model, and demonstrate the power of physiologically
      based modeling by correctly predicting sleep latency times following deprivation
      from experimental data.

PMID- 18805428
TI  - An agent-based model for predicting the prevalence of Trypanosoma cruzi I and II
      in their host and vector populations.
AB  - Trypanosoma cruzi is the causative agent of Chagas disease, an endemic human
      parasitosis in Latin America. This protozoan is transmitted to human and other
      mammals by blood-feeding bugs belonging to the Triatominae subfamily. There are
      two strains (T. cruzi I and T. cruzi II) presenting different biological and
      ecological characteristics. An original agent-based model (ABM) was designed for
      predicting the prevalence (i.e., proportion of infected individuals in the total
      population at a given time) of T. cruzi I and II during single and mixed
      infections. The ABM was calibrated from experimental data retrieved from
      literature. It was shown that inclusion of reservoir hosts as supplementary type
      of agent in the model was necessary for obtaining realistic simulation results of
      the prevalence of the two strains. This is totally in agreement with experimental
      and field observations on the importance of reservoirs in the parasite
      transmission cycle. Proposals were made for refining the model. More generally,
      the advantages and limitations of the ABM in parasitology modeling have been
      discussed.

PMID- 18805429
TI  - Corticotropin-releasing hormone acts on CRH-R1 to inhibit the spontaneous
      contractility of non-labouring human myometrium at term.
AB  - AIMS: Corticotropin-releasing hormone (CRH) has been implicated in the mechanisms
      controlling human parturition. The aims of the present study were to explore
      effects of CRH on contractility of human term myometrium and compare these
      effects in labouring and non-labouring myometrial strips. MAIN METHODS: The
      cumulative effects of CRH (10(-10) to 10(-7) mol/l) on the spontaneous
      contractility of labouring and non-labouring myometrial samples were evaluated
      using isometric tension recordings. KEY FINDINGS: CRH exhibited a concentration
      dependent relaxant effect on spontaneous contractions in non-labouring term
      myometrium. This effect was mediated principally via a reduction in the amplitude
      rather than any changes in the frequency of contractions. The CRH-induced
      inhibitory effect on contractility could be blocked by pre-treatment with a CRH
      R1 antagonist antalarmin, but not by pre-treatment with the CRH-R2 antagonist
      astressin 2B. CRH had no effect on spontaneous contractions in the labouring
      myometrium, as no change in either the amplitude or the frequency was observed.
      SIGNIFICANCE: Our findings indicate that CRH acts on CRH-R1 to inhibit
      spontaneous contractions in term myometrium from women who were not undergoing
      labour, but not those who were undergoing labour, supporting the hypothesis that
      CRH exerts dual effect on myometrium during pregnancy.

PMID- 18805430
TI  - Low density lipoproteins transactivate EGF receptor: role in mesangial cell
      proliferation.
AB  - Hyperlipidemia and the glomerular accumulation of atherogenic lipoproteins (low
      density lipoprotein, LDL; and its oxidatively-modified variants, ox-LDL) are
      commonly associated with the development of glomerular mesangial proliferative
      diseases. However, cellular signaling mechanisms by which atherogenic
      lipoproteins stimulate mesangial cell proliferation are poorly defined. In this
      study, we examined the effect of atherogenic lipoproteins on the activation of
      mesangial cell epidermal growth factor (EGF) receptor, mitogen activated protein
      kinase (MAP kinase), Ras, and mesangial cell proliferation. Stimulation of
      mesangial cells with LDL, and with greater activity, ox-LDL, markedly induced the
      transactivation of EGF receptor within 5 min of stimulation; the effect persisted
      up to at least 60 min LDL, and with a greater degree, ox-LDL, increased the
      activation of Ras, MAP kinase, and mesangial cell proliferation. Inhibition of
      EGF receptor kinase activity and/or MAP kinase activation blocked both LDL- and
      ox-LDL-induced mesangial cell proliferation. We suggest that the accumulation of
      LDL and more potently its oxidized forms within the glomerulus, through the
      transactivation of EGF receptor, stimulate down-stream Ras-MAP kinase signaling
      cascade leading to mesangial cell proliferation. Regulation of glomerular
      accumulation of atherogenic lipoproteins and/or EGF receptor signaling may
      provide protective environment against mesangial hypercellularity seen in
      glomerular diseases.

PMID- 18805431
TI  - Statistical interpretation of the interplay between noise and chaos in the
      stochastic logistic map.
AB  - A recurring problem in population biology--as well as other stochastic dynamical
      systems in biology, the physical and social sciences--is the distinction between
      the 'true' dynamics of a system and observational noise: i.e. can we from present
      data reliably infer e.g. biological mechanisms, or are signals swamped by noise.
      Here, we approach this problem using the canonical model for simple systems that
      exhibit complex behaviour, the logistic map. At each time-point noise is added,
      which allows us to study the long-term behaviour of a system which exhibits both
      non-linear dynamics and intrinsic noise. We show that the interplay between
      deterministic non-linear dynamics and simple Gaussian noise results in a
      perplexingly simple system when viewed statistically. In particular we show that
      for the case of Gaussian noise it is possible to derive at very reliable
      approximations for the time until the system has reached an absorbing state. This
      generic model allows us, for example, to study the life-time of molecular species
      involved in noisy feedback loops.

PMID- 18805432
TI  - The Ross-Macdonald model in a patchy environment.
AB  - We generalize to n patches the Ross-Macdonald model which describes the dynamics
      of malaria. We incorporate in our model the fact that some patches can be vector
      free. We assume that the hosts can migrate between patches, but not the vectors.
      The susceptible and infectious individuals have the same dispersal rate. We
      compute the basic reproduction ratio R(0). We prove that if R(0)1, then the
      disease-free equilibrium is globally asymptotically stable. When R(0)>1, we prove
      that there exists a unique endemic equilibrium, which is globally asymptotically
      stable on the biological domain minus the disease-free equilibrium.

PMID- 18805433
TI  - The anti-cancer drug lenalidomide inhibits angiogenesis and metastasis via
      multiple inhibitory effects on endothelial cell function in normoxic and hypoxic
      conditions.
AB  - Lenalidomide (Revlimid) is approved for the treatment of transfusion-dependent
      patients with anemia due to low- or intermediate-1-risk Myelodysplastic Syndromes
      (MDS) associated with a del 5q cytogenetic abnormality with or without additional
      cytogenetic abnormalities, and in combination with dexamethasone for the
      treatment of multiple myeloma patients who have received at least one prior
      therapy. Previous reports suggest that lenalidomide is anti-angiogenic and this
      property appears to be related to efficacy in patients with MDS. We have
      investigated the effect of lenalidomide on the formation of microvessels in a
      novel in vitro angiogenesis assay utilizing human umbilical arterial rings and in
      a capillary-like cord formation assay using cultured primary endothelial cells.
      We found that lenalidomide consistently inhibits both sprout formation by
      arterial rings and cord formation by endothelial cells in a dose-dependent
      manner. We also found an inhibitory effect of lenalidomide on the associations
      between cadherin 5, beta-catenin and CD31, adherens junction proteins whose
      interaction is critical for endothelial cell cord formation. Furthermore,
      lenalidomide inhibited VEGF-induced PI3K-Akt pathway signaling, which is known to
      regulate adherens junction formation. We also found a strong inhibitory effect of
      lenalidomide on hypoxia-induced endothelial cell formation of cords and HIF-1
      alpha expression, the main mediator of hypoxia-mediated effects and a key driver
      of angiogenesis and metastasis. Anti-metastatic activity of lenalidomide in vivo
      was confirmed in the B16-F10 mouse melanoma model by a >40% reduction in melanoma
      lung colony counts versus untreated mice. Our results suggest that inhibitory
      effects on microvessel formation, in particular adherens junction formation and
      inhibition of hypoxia-induced processes support a potential anti-angiogenic and
      anti-metastatic mechanism for this clinically active drug.

PMID- 18805434
TI  - A tale of two recognition systems: implications of the fusiform face area and the
      visual word form area for lateralized object recognition models.
AB  - Two areas of current intense interest in the neuroimaging literature are that of
      the visual word form area (VWFA) and of the fusiform face area (FFA) and their
      roles in word and face perception, respectively. These two areas are of
      particular relevance to laterality research because visual word identification
      and face identification have long been shown to be especially lateralized to the
      left hemisphere and the right hemisphere, respectively. This review therefore
      seeks to evaluate their significance for the broader understanding of
      lateralization of object recognition. A multi-level model of lateralized object
      recognition is proposed based on a combination of behavioral and neuroimaging
      findings. Rather than seek to characterize hemispheric asymmetries according to a
      single principle (e.g., serial-parallel), it is suggested that current
      observations can be understood in terms of three asymmetric levels of processing,
      using the framework of the Janus model of hemispheric function. It is suggested
      that the left hemisphere represents features using an abstract-category code
      whereas the RH utilizes a specific-exemplar code. The relationships between these
      features are also coded asymmetrically, with the LH relying on associative co
      occurrence values and the RH relying on spatial metrics. Finally, the LH
      controlled selection system focuses on isolating features and the RH focuses on
      conjoining features. It is suggested that each hemisphere utilizes efficient
      (apparently parallel) processing when stimuli are congruent with its preferred
      processing style and inefficient (apparently serial) processing when they are
      not, resulting in the typical left-lateralization for orthographic analysis and
      right-lateralization for face analysis.

PMID- 18805435
TI  - Nicotine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone induce cyclooxygenase
      2 activity in human gastric cancer cells: Involvement of nicotinic acetylcholine
      receptor (nAChR) and beta-adrenergic receptor signaling pathways.
AB  - Induction of cyclooxygenase-2 (COX-2) associates with cigarette smoke exposure in
      many malignancies. Nicotine and its derivative, 4-(methylnitrosamino)-1-(3
      pyridyl)-1-butanone (NNK), are the two important components in cigarette smoke
      that contributes to cancer development. However, the molecular mechanism(s) by
      which nicotine or NNK promotes gastric carcinogenesis remains largely unknown. We
      found that nicotine and NNK significantly enhanced cell proliferation in AGS
      cells that expressed both alpha7 nicotinic acetylcholine receptor (alpha7 nAChR)
      and beta-adrenergic receptors. Treatment of cells with alpha-bungarotoxin (alpha
      BTX, alpha7nAChR antagonist) or propranolol (beta-adrenergic receptor antagonist)
      blocked NNK-induced COX-2/PGE(2) and cell proliferation, while nicotine-mediated
      cell growth and COX-2/PGE(2) induction can only be suppressed by propranolol, but
      not alpha-BTX. Moreover, in contrast to the dependence of growth promoting effect
      of nicotine on Erk activation, inhibitor of p38 mitogen-activated protein kinase
      (MAPK) repressed NNK-induced COX-2 upregulation and resulted in suppression of
      cell growth. In addition, nicotine and NNK mediated COX-2 induction via different
      receptors to modulate several G1/S transition regulatory proteins and promote
      gastric cancer cell growth. Selective COX-2 inhibitor (SC-236) caused G1 arrest
      and abrogated nicotine/NNK-induced cell proliferation. Aberrant expression of
      cyclin D1 and other G1 regulatory proteins are reversed by blockade of COX-2.
      These results pointed to the importance of adrenergic and nicotinic receptors in
      gastric tumor growth through MAPK/COX-2 activation, which may perhaps provide a
      chemoprevention strategy for cigarette smoke-related gastric carcinogenesis.

PMID- 18805436
TI  - Allosteric modulation of NMDA receptor via elevation of brain glycine and D
      serine: the therapeutic potentials for schizophrenia.
AB  - Ionotropic AMPA and NMDA glutamate receptors are ligand-gated ion channels that
      mediate fast synaptic transmission in the brain and play a crucial role in
      learning and memory. Dysfunction of these receptors is believed to be associated
      with a number of neuropsychiatric disorders, including schizophrenia. As direct
      activation of these ionotropic receptors can lead to excitoxicity, allosteric
      modulation of these receptors could minimize side-effects to achieve better
      therapeutic efficacy. Our review here focuses on the allosteric modulation of the
      NMDA receptor. Endogenous glycine and D-serine both act as co-agonists on the
      strychnine-insensitive GlyB site on the NMDA receptor, and along with glutamate,
      co-activate the NMDA receptor. Forebrain synaptic glycine and d-serine levels are
      regulated by the Glycine Transporter-1 (GlyT1) and the arginine-serine-cysteine
      transporter-1 (Asc-1), respectively; in addition to D-serine metabolism by D
      Amino Acid Oxidase (DAAO). Together, these processes prevent the GlyB site from
      being saturated by the high extracellular levels of brain glycine, and perhaps d
      serine, in vivo. Blockade of NMDA receptors by phencyclidine induces
      schizophrenia-like symptoms with the associated cognitive deficits. It was
      proposed that: a) blockade of GlyT1 mediated reuptake of glycine, or b)
      inhibition of D-amino Acid Oxidase, or Asc-1 will elevate brain glycine, and D
      serine to upregulate NMDA receptor functions via glycine and D-serine co
      agonistic allosteric modulation of the GlyB sites on the NMDA receptor. These
      approaches may provide novel treatments to schizophrenia, provided that some of
      the known adverse effects associated with existing GlyT1 agents can be safely and
      adequately dealt with.

PMID- 18805437
TI  - Interplay between lipids and the proteinaceous membrane fusion machinery.
AB  - For membrane fusion to occur, opposed lipid bilayers initially establish a fusion
      pore, often followed by complete mixing of the fusing membranes. Contemporary
      views suggest that during fusion lipid bilayers are continuous passive platforms
      that are disrupted and remodeled by catalytic proteins. Some models propose that
      even the architecture and composition of the fusion pore might be dominated by
      proteins rather than lipids. Hence, lipids have no regulatory contribution to
      this process; they simply adapt their shape passively for filling space between
      otherwise autonomous protein machineries. However, an increasing number of
      experimental findings indicate that membrane fusion critically depends on a
      variety of lipids and lipid derivatives. Therefore, a purely proteocentric view
      describes fusion mechanisms insufficiently. Instead, lipids have functions
      probably at different levels, as (i) a general influence on the propensity of
      lipid bilayers to fuse, (ii) a role in recruiting exocytotic proteins to the
      plasma membrane, (iii) a role in organizing membrane domains for fusion and (iv)
      direct regulatory effects on fusion protein complexes. In this review we have
      made an attempt to bring together the large body of evidence supporting a major
      role for lipids in membrane fusion either directly or indirectly.

PMID- 18805438
TI  - Assessing gait impairment following experimental traumatic brain injury in mice.
AB  - Although gait disturbance is frequently documented among patients with traumatic
      brain injury (TBI), gait data from animal models of TBI are lacking. To determine
      the effect of TBI on gait function in adult mice, we assessed gait changes
      following unilateral controlled cortical impact (CCI) using a computer-assisted
      automated gait analysis system. Three days after CCI, intensity, area or width of
      paw contact were significantly decreased in forepaw(s) while the relative paw
      placement between the fore and hindpaws altered, suggesting that TBI affected
      sensorimotor status and reduced interlimb coordination. Similar to TBI patients,
      CCI decreased gait velocity and stride length, and prolonged stance and swing
      phase in mice. Following CCI, step pattern was also changed with increasing use
      in the ipsilateral-diagonal limb sequence. Our results indicate that gait
      analysis provides great insight into both spatial and temporal aspects of limb
      function changes during overground locomotion in quadruped species with head
      injury that are valuable for the purpose of treatment and rehabilitation. Our
      study also provides additional functional validation for the established mouse
      CCI model that is relevant to human head injury.

PMID- 18805439
TI  - Resolving sub-synaptic compartments with double immunofluorescence labeling in
      hippocampal neurons.
AB  - Immunofluorescence microscopy of synaptic proteins is a powerful and commonly
      used approach in cellular neurosciences. Many studies use green/red color
      overlays of immunofluorescence images to demonstrate synaptic co-localization of
      an unknown protein with a known synaptic marker. However, this approach fails to
      identify the specific sub-synaptic compartment in which a protein is localized.
      Here we describe a novel analysis method to determine the precise location of
      proteins within synapses of cultured hippocampal neurons with double
      immunofluorescence staining. This approach is based on center-to-center distance
      measurements of fluorescent clusters of protein pairs coexisting in synapses. We
      validated the method by analyzing the distances between different combinations of
      well-established synaptic marker proteins. The results demonstrate that protein
      pairs in the active zone and the postsynaptic density, two sub-synaptic
      compartments which are separated by less than 50 nm, can be readily distinguished
      from each other and from marker pairs co-localized within a single sub-synaptic
      compartment. Thus, center-to-center distance analysis can resolve the distance
      across the synaptic cleft and it is useful for localizing synaptic proteins to
      specific pre- and postsynaptic compartments.

PMID- 18805440
TI  - DNA methylation and TLR9 ligands: not only a matter of semantics.

PMID- 18805441
TI  - Experimental sleep fragmentation and sleep deprivation in rats increases
      exploration in an open field test of anxiety while increasing plasma
      corticosterone levels.
AB  - Sleep deprivation alters mood and anxiety in man. In rats, 24 h of treadmill
      induced total sleep deprivation or sleep fragmentation increased exploratory
      behavior in an open field test of anxiety compared to cage or exercise controls.
      Plasma corticosterone (CORT) levels of sleep disturbed and exercise control rats
      were elevated compared to cage controls, suggesting that the increased
      exploration observed in the sleep disturbed rats was not due to a hypothalamic
      pituitary-adrenal (HPA) stress response.

PMID- 18805442
TI  - Differential effects of 5-HT2C receptor activation by WAY 161503 on nicotine
      induced place conditioning and locomotor activity in rats.
AB  - RATIONALE: Numerous studies indicate a role for both the serotonin 2C receptor (5
      HT(2C)) and the nicotinic acetylcholine receptor in locomotion, reinforcement and
      motivated behaviours. Nicotine, a potent nicotinic acetylcholine receptor
      agonist, interacts with the dopaminergic and serotonergic systems and is known to
      positively affect reward-related behaviours. OBJECTIVES: The current study
      examined the effects of 5-HT(2C) receptor activation on nicotine-induced (0.6
      mg/kg) place conditioning and spontaneous locomotion. METHODS: Using Sprague
      Dawley rats, the effects of the selective 5-HT(2C) receptor agonist WAY 161503 (0
      1.0 mg/kg) and the selective 5-HT(2C) receptor antagonist SB 242084 (1.0 mg/kg)
      alone, in combination, and on nicotine-induced (0.6 mg/kg) spontaneous locomotor
      activity were assessed. The effects of WAY 161503 (1.0, 3.0 mg/kg) were also
      investigated in nicotine-induced place conditioning using a two-compartment
      biased design; amphetamine (1.0 mg/kg) served as a positive control. As
      differential effects were observed between place conditioning and locomotor
      activity, the subjects used in the place conditioning experiments were also
      tested for effects on locomotor activity. RESULTS: WAY 161503 decreased baseline
      and nicotine-induced locomotor activity at the highest dose tested (1.0mg/kg) and
      these effects were attenuated by SB 242084. Amphetamine and nicotine both induced
      robust place preferences and WAY 161503 did not have any effects in the context
      of place conditioning. In contrast, WAY 161503 (1.0 mg/kg) blocked nicotine
      induced locomotor activity. CONCLUSIONS: These results suggest that 5-HT(2C)
      receptors may play an inhibitory role in nicotine-induced locomotor activity, but
      do not appear to influence place conditioning under the current conditions.

PMID- 18805443
TI  - Functional characteristics of auditory cortex in the blind.
AB  - We used functional magnetic resonance imaging (fMRI) to examine responses within
      auditory cortical fields during the passive listening of pure tone (PT) and
      frequency modulated (FM) stimuli in seven early blind (EB), five late blind (LB)
      and six sighted control (SC) individuals. Subjects were scanned using a "sparse
      sampling" imaging technique while listening to PT and FM sounds presented at
      either low (400 Hz) or high (4 kHz) center frequencies. When high tones were
      directly compared to low tones, the resulting activation maps showed a general
      tonotopic organization within the superior and middle temporal lobes at
      statistically significant thresholds for the SC and LB groups while the EB group
      showed a comparable tonotopic organization but only at statistically non
      significance thresholds. A contrast of all tonal stimuli to a quiet baseline
      similarly revealed significantly less signal volume in the EB than in either the
      LB or SC groups. These results suggest that EB does not alter inherent patterns
      of tonotopic organization but rather, under low-demand listening conditions,
      results in a more efficient processing of simple auditory stimuli within the
      early stages of the auditory hierarchy. While these effects must be interpreted
      cautiously due to the small sample sizes, they indicate that functional responses
      in auditory cortical areas are altered by visual deprivation and that intramodal
      auditory plasticity may underlie previously reported auditory advantages observed
      in the blind.

PMID- 18805444
TI  - Early adhesion induces interaction of FAK and Fyn in lipid domains and activates
      raft-dependent Akt signaling in SW480 colon cancer cells.
AB  - Integrin-dependent interaction of epithelial tumor cells with extracellular
      matrix (ECM) is critical for their migration, but also for hematogenous
      dissemination. Elevated expression and activity of Src family kinases (SFKs) in
      colon cancer cells is often required in the disease progression. In this work, we
      highlighted how focal adhesion kinase (FAK) and SFKs interacted and we analyzed
      how PI3K/Akt and MAPK/Erk1/2 signaling pathways were activated in early stages of
      colon cancer cell adhesion. During the first hour, integrin engagement triggered
      FAK-Y397 phosphorylation and a fraction of FAK was located in lipid
      rafts/caveolae domains where it interacted with Fyn. The FAK-Y861 and/or -Y925
      phosphorylations led to a subsequently FAK translocation out of lipid domains. In
      parallel, a PI3K/Akt pathway dependent of lipid microdomain integrity was
      activated. In contrast, the MAPK/Erk1/2 signaling triggered by adhesion increased
      during at least 4 h and was independent of cholesterol disturbing. Thus, FAK/Fyn
      interaction in lipid microdomains and a Akt-1 activation occurred at the same
      time during early contact with ECM suggesting a specific signaling dependent of
      lipid rafts/caveolae domains.

PMID- 18805445
TI  - Darwin's evolution theory, brain oscillations, and complex brain function in a
      new "Cartesian view".
AB  - Comparatively analyses of electrophysiological correlates across species during
      evolution, alpha activity during brain maturation, and alpha activity in complex
      cognitive processes are presented to illustrate a new multidimensional "Cartesian
      System" brain function. The main features are: (1) The growth of the alpha
      activity during evolution, increase of alpha during cognitive processes, and
      decrease of the alpha entropy during evolution provide an indicator for evolution
      of brain cognitive performance. (2) Human children younger than 3 years are
      unable to produce higher cognitive processes and do not show alpha activity till
      the age of 3 years. The mature brain can perform higher cognitive processes and
      demonstrates regular alpha activity. (3) Alpha activity also is significantly
      associated with highly complex cognitive processes, such as the recognition of
      facial expressions. The neural activity reflected by these brain oscillations can
      be considered as constituent "building blocks" for a great number of functions.
      An overarching statement on the alpha function is presented by extended analyzes
      with multiple dimensions that constitute a "Cartesian Hyperspace" as the basis
      for oscillatory function. Theoretical implications are considered.

PMID- 18805446
TI  - Delivery of serotonin to the brain by monocytes following phagocytosis of
      liposomes.
AB  - Many drugs are not able to enter the brain due to the presence of the blood-brain
      barrier (BBB) and therefore cannot be used in the treatment of diseases of the
      brain. Since it is now known that the brain is under immunological surveillance,
      we hypothesized that phagocytic cells of the innate immune system, mainly
      neutrophils and monocytes, can be exploited as transporters of drugs to the
      brain. To target circulating mononuclear phagocytic cells, negatively-charged
      nano-sized liposomes were formulated encapsulating serotonin, a BBB impermeable
      neurological drug. Brain uptake, biodistribution, and the mechanism of brain
      transport were examined in vitro and in rats and rabbits by utilizing double
      radiolabeled (3)H (in the membrane) and (14)C-serotonin (in the core), and
      liposomes with fluorescent markers (membrane and core). The brain uptake of
      liposomal serotonin was significantly higher (0.138%+/-0.034 and 0.097%+/-0.011,
      vs. 0.068%+/-0.02 and 0.057%+/-0.01, 4 h and 24 h after IV administration in
      rats, serotonin liposomes and in solution, respectively). The same brain uptake
      of both empty and serotonin liposomes, the co-localization in the brain of both
      markers, and the unchanged ratio of (3)H:(14)C suggest that intact liposomes
      entered the brain. Since treatment of animals by liposomal alendronate resulted
      with inhibition of monocytes but not of neutrophils, and with no brain delivery,
      it is suggested that monocytes are the main transporters of liposomes to the
      brain.

PMID- 18805447
TI  - The anti-inflammatory effect of neuropeptide Y (NPY) in rats is dependent on
      dipeptidyl peptidase 4 (DP4) activity and age.
AB  - Neuropeptide Y (NPY)-induced modulation of the immune and inflammatory responses
      is regulated by tissue-specific expression of different receptor subtypes (Y1-Y6)
      and the activity of the enzyme dipeptidyl peptidase 4 (DP4, CD26) which
      terminates the action of NPY on Y1 receptor subtype. The present study
      investigated the age-dependent effect of NPY on inflammatory paw edema and
      macrophage nitric oxide production in Dark Agouti rats exhibiting a high-plasma
      DP4 activity, as acknowledged earlier. The results showed that NPY suppressed paw
      edema in adult and aged, but not in young rats. Furthermore, plasma DP4 activity
      decreased, while macrophage DP4 activity, as well as macrophage CD26 expression
      increased with aging. The use of NPY-related peptides and Y receptor-specific
      antagonists revealed that anti-inflammatory effect of NPY is mediated via Y1 and
      Y5 receptors. NPY-induced suppression of paw edema in young rats following
      inhibition of DP4 additionally emphasized the role for Y1 receptor in the anti
      inflammatory action of NPY. In contrast to the in vivo situation, NPY stimulated
      macrophage nitric oxide production in vitro only in young rats, and this effect
      was mediated via Y1 and Y2 receptors. It can be concluded that age-dependant
      modulation of inflammatory reactions by NPY is determined by plasma, but not
      macrophage DP4 activity at different ages.

PMID- 18805449
TI  - 1-Methyl-4-phenyl-pyridinium ion-induced oxidative stress, c-Jun phosphorylation
      and DNA fragmentation factor-45 cleavage in SK-N-SH cells are averted by
      selegiline.
AB  - Parkinson's disease is a progressive neurodegenerative disorder, associated with
      the selective loss of dopaminergic neurons in the substantia nigra pars compacta.
      Recent studies have shown that c-Jun-N terminal kinase pathways might be involved
      in the oxidative stress-induced neuronal demise. In addition, there are several
      studies demonstrating that selegiline protects neural cell degeneration. In view
      of the above, the toxic effects of MPP(+) and the protective roles of selegiline
      were studied in cultures of human neuroblastoma (SK-N-SH) cell lines in the
      present study. MPP(+) significantly decreased cell viability but increased
      reactive oxygen species formation and lipid peroxidation, and the said effects
      were attenuated by selegiline. MPP(+) did not change the total levels of c-Jun
      but enhanced phosphorylation of c-Jun at Ser73 and cleavage of DNA fragmentation
      factor 45, which were diminished by selegiline. MPP(+)-treated SK-N-SH cells
      exhibited an irregularly shaped nuclear chromatin or DNA fragmentation, which was
      abolished by selegiline. These data suggest that c-Jun-N terminal kinase pathways
      are involved in oxidative stress-induced dopaminergic neuronal degeneration and
      pretreatment with selegiline affords neuroprotection by inhibiting these cell
      death-signaling pathways.

PMID- 18805448
TI  - Ubiquitination-mediated internalization and degradation of the astroglial
      glutamate transporter, GLT-1.
AB  - Sodium-dependent glutamate uptake is essential for limiting excitotoxicity, and
      dysregulation of this process has been implicated in a wide array of neurological
      disorders. The majority of forebrain glutamate uptake is mediated by the
      astroglial glutamate transporter, GLT-1. We and others have shown that this
      transporter undergoes endocytosis and degradation in response to activation of
      protein kinase C (PKC), however, the mechanisms involved remain unclear. In the
      current study, transfected C6 glioma cells or primary cortical cultures were used
      to show that PKC activation results in incorporation of ubiquitin into GLT-1
      immunoprecipitates. Mutation of all 11 lysine residues in the amino and carboxyl
      terminal domains to arginine (11R) abolished this signal. Selective mutation of
      the seven lysine residues in the carboxyl terminus (C7K-R) did not eliminate
      ubiquitination, but it completely blocked PKC-dependent internalization and
      degradation. Two families of variants of GLT-1 were prepared with various lysine
      residues mutated to arginine. Analyses of these constructs indicated that
      redundant lysine residues in the carboxyl terminus were sufficient for the
      appearance of ubiquitinated product and degradation of GLT-1. Together these data
      define a novel mechanism by which the predominant forebrain glutamate transporter
      can be rapidly targeted for degradation.

PMID- 18805450
TI  - Age-related alterations of Nestin-immunoreactive neurons in rat basal forebrain
      with aged memory deficit.
AB  - Age-related and aged memory deficit changes in Nestin-immunoreactive (Nestin-IR)
      neurons were studied following recent evidence of distinct Nestin-IR neurons
      within adult rat basal forebrain. Morris water maze task assessed spatial
      learning capacity of 3- and 24-month rats (aged-impaired and aged-unimpaired
      groups). Nestin-IR neuron distributional and morphological features were
      investigated by immunohistochemistry and positive neuronal number calculation.
      Nestin-IR neuron number declined with aging, especially aged-impaired.
      Significant negative correlations existed between average escape latencies and
      Nestin-IR neuron number in medial septum-diagonal band of Broca (MS-DBB).
      Correlations of rostral portion [medial septum (MS) and vertical limb diagonal
      band (vDB)] were higher than caudal portion [horizontal limb diagonal band
      (hDB)]. Aged-impaired showed reduced complexity of Nestin-IR neuron dendrite
      arborization and dendritic length. Nestin-IR astrocyte-like cells appeared
      scattered among Nestin-IR neurons on some aged-impaired slices. In conclusion,
      aged-impaired rats showed worse cognitive spatial performance and less Nestin-IR
      neuronal number compared to aged-unimpaired. Nestin-IR neuronal loss and
      morphological changes are some pathological characteristics of rat aged basal
      forebrain and may be important in neurobiological mechanisms of brain aging and
      aged memory deficit.

PMID- 18805451
TI  - Role of sodium ferulate in the nociceptive sensory facilitation of neuropathic
      pain injury mediated by P2X(3) receptor.
AB  - Neuropathic pain usually is persistent and no effective treatment. ATP plays an
      important role in the initiation of pain. P2X(3) receptors are localized in the
      dorsal root ganglion (DRG) neurons and activated by extracellular ATP. Sodium
      ferulate (SF) is an active principle from Chinese herbal medicine and has anti
      inflammatory activities. This study observed the effects of SF on the nociceptive
      facilitation of the primary sensory afferent after chronic constriction injury
      (CCI) mediated by P2X(3) receptor. In this study, the content of ATP in DRG
      neurons was measured by high-performance liquid chromatography (HPLC). P2X(3)
      agonist-activated currents in DRG neurons was recorded by the whole-cell patch
      clamp skill. The expression of P2X(3) mRNA in DRG neurons was analyzed by in situ
      hybridization. The ATP content of DRG was increased after CCI. In CCI rats
      treated with SF, the content of ATP in DRG neurons was reduced. SF decreased the
      increment of P2X(3) agonist-activated currents and P2X(3) mRNA expression in DRG
      neurons during CCI. SF may inhibit the initiation of pain and primary afferent
      sensitization mediated by P2X(3) receptor during CCI.

PMID- 18805452
TI  - Towards a human oral vaccine for anthrax: the utility of a Salmonella Typhi Ty21a
      based prime-boost immunization strategy.
AB  - We previously demonstrated the ability of an orally administered attenuated
      Salmonella enterica serovar Typhimurium strain expressing the protective antigen
      (PA) of Bacillus anthracis to confer protection against lethal anthrax aerosol
      spore challenge [Stokes MG, Titball RW, Neeson BN, et al. Oral administration of
      a Salmonella enterica-based vaccine expressing Bacillus anthracis protective
      antigen confers protection against aerosolized B. anthracis. Infect Immun
      2007;75(April (4)):1827-34]. To extend the utility of this approach to humans we
      constructed variants of S. enterica serovar Typhi Ty21a, an attenuated typhoid
      vaccine strain licensed for human use, which expressed and exported PA via two
      distinct plasmid-based transport systems: the Escherichia coli HlyA haemolysin
      and the S. Typhi ClyA export apparatus. Murine immunogenicity studies confirmed
      the ability of these constructs, especially Ty21a expressing the ClyA-PA fusion
      protein, to stimulate strong PA-specific immune responses following intranasal
      immunization. These responses were further enhanced by a subsequent boost with
      either parenterally delivered recombinant PA or the licensed US human alum
      adsorbed anthrax vaccine (AVA). Anthrax toxin neutralizing antibody responses
      using this prime-boost regimen were rapid, vigorous and broad in nature. The
      results of this study demonstrate the feasibility of employing a mucosal prime
      with a licensed Salmonella Typhi vaccine strain followed by a parenteral protein
      boost to stimulate rapid protective immunity against anthrax.

PMID- 18805453
TI  - Country recommendations on the inclusion of HPV vaccines in national immunization
      programmes among high-income countries, June 2006-January 2008.
AB  - We analysed country recommendations and funding plans finalized through January
      2008 for the inclusion of quadrivalent and bivalent human papillomavirus (HPV)
      vaccines in national immunization programmes. Fifteen industrialized countries
      have recommended HPV vaccine use based on careful review of scientific evidence
      and cost-effectiveness. There was a strong consensus among the guidelines
      regarding assessment of vaccine safety and efficacy, selection of primary target
      populations for vaccination, vaccine delivery strategies, and the need for
      vaccinated females to seek cervical cancer screening. The analysis informs
      ongoing discussions in several countries considering HPV vaccines for national
      immunization programmes and discussions at the World Health Organization about
      global recommendations for HPV vaccine use for national immunization programmes.

PMID- 18805454
TI  - A prime-boost vaccination protocol optimizes immune responses against the
      nucleocapsid protein of the SARS coronavirus.
AB  - Severe acute respiratory syndrome (SARS) is a serious infectious disease caused
      by the SARS coronavirus. We assessed the potential of prime-boost vaccination
      protocols based on the nucleocapsid (NC) protein co-administered with a
      derivative of the mucosal adjuvant MALP-2 or expressed by modified Vaccinia virus
      Ankara (MVA-NC) to stimulate humoral and cellular immune responses at systemic
      and mucosal levels. The obtained results demonstrated that strong immune
      responses can be elicited both at systemic and mucosal levels following a
      heterologous prime-boost vaccination protocol consisting in priming with NC
      protein add-mixed with MALP-2 by intranasal route and boosting with MVA-NC by
      intramuscular route.

PMID- 18805455
TI  - Nationwide measles epidemic in Ukraine: the effect of low vaccine effectiveness.
AB  - The WHO European Region has a measles elimination target for 2010. Between
      September 2005 and mid-June 2006, more than 50,000 measles cases were reported in
      Ukraine; many reportedly had received two doses of measles vaccine and over 60%
      were among persons 15-29 years old. To investigate vaccine effectiveness (VE), a
      case-control study was undertaken in Dnepropetrovsk region. VE for two doses of
      measles vaccine was 93.1%, providing insufficient population immunity for measles
      elimination. An additional dose of measles vaccine for these age-cohorts is
      required if Ukraine is to achieve measles elimination. Other republics of the
      former Soviet Union also need to consider a supplemental dose of measles vaccine
      for older age groups identified epidemiologically to be at increased risk for
      measles even though individuals may have already received two doses.

PMID- 18805456
TI  - Applicability, reliability, sensitivity, and specificity of six Brighton
      Collaboration standardized case definitions for adverse events following
      immunization.
AB  - We evaluated the applicability, reliability, sensitivity, and specificity of six
      standardized case definitions for adverse events following immunization (AEFI)
      (for fever, generalized convulsive seizure, hypotonic-hyporesponsive episode,
      intussusception, nodule, and persistent crying) developed by the Brighton
      Collaboration using the U.S. Vaccine Adverse Event Reporting System (VAERS). The
      evaluation included: (a) the development of codified search strings using
      standardized coding terminology, and (b) for sensitivity and specificity
      analyses, the development of a "gold standard" for case determination by clinical
      expert reviews, and its comparison against the application of the definitions to
      VAERS reports by nonclinicians. Application of the case definitions in an
      automated approach proved to be valid, feasible, and unlikely to miss confirmed
      cases of the reported clinical event. The definitions had variable but generally
      high sensitivity and specificity compared to clinician review, which in itself
      yielded inconsistent case determination. The study demonstrated the need for the
      developed standardized definitions for AEFI and their usefulness in passive
      surveillance.

PMID- 18805457
TI  - Attenuated West Nile viruses bearing 3'SL and envelope gene substitution
      mutations.
AB  - Four viable West Nile (WN) 3'SL-mutant viruses were evaluated for
      neuroinvasiveness and neurovirulence in mice. All mutants were highly attenuated
      for neuroinvasiveness. However, only one of these four (WNmutE virus) was
      significantly attenuated for neurovirulence. To attenuate WNmutE virus further,
      we introduced five substitution mutations into the envelope (env) gene segment in
      wild-type (wt) WN and WNmutE genomes, based on differences in the env gene
      sequence between the live Japanese encephalitis vaccine (SA14-14-2) and its
      virulent parent. The env gene mutations had an attenuating effect in the context
      of the wt WNV genome but only a marginal enhancing effect on the attenuation of
      WNmutE virus.

PMID- 18805458
TI  - gp130 signaling in bone cell biology: multiple roles revealed by analysis of
      genetically altered mice.
AB  - The receptor subunit gp130 is utilized by a wide range of cytokines, many of
      which have critical functions in regulating the actions of osteoclasts and
      osteoblasts. In vitro studies have revealed remarkably consistent effects of many
      of these family members, specifically, actions on receptors in the osteoblast
      lineage that stimulate osteoblast differentiation and stimulate production of
      RANKL, thereby increasing the formation of osteoclasts. In contrast to this
      simple model of gp130 action on bone, deletion of cytokines or receptors that
      interact with gp130 reveal a range of bone phenotypes implicating critical roles
      for gp130 signaling in longitudinal bone growth, bone resorption and bone
      formation. In most cases, deletion of gp130, ligands or ligand-specific receptors
      interacting with gp130 causes a low level of bone formation; a high level of bone
      formation was only observed in gp130(Y757F/Y757F) mice, gp130 signaling mutants,
      where it is caused by a cell-lineage autonomous increase in osteoclast formation
      and an IL-6-dependent coupling pathway. On the other hand, the range of gene
      knockouts may cause either a reduction or an increase in osteoclast formation,
      and in many cases alterations in osteoclast size and ability to resorb bone.
      Since some knockouts are neonatal lethal, interpretation of ex vivo analyses and
      the contribution of each component to bone remodeling are not clearly defined,
      and there is still much work to be done before these questions can be resolved.
      Taken together these results indicate multiple roles for gp130 cytokines in
      controlling osteoblasts and osteoclast function, including paracrine roles to
      mediate signaling between these two cell types.

PMID- 18805459
TI  - Spatiotemporal characteristics of pain-associated neuronal activities in primary
      somatosensory cortex induced by peripheral persistent nociception.
AB  - The primary somatosensory cortex (S1 area) is one of the key brain structures for
      central processing of somatic noxious information to produce pain perception.
      However, so far, the spatiotemporal characteristics of neuronal activities
      associated with peripheral persistent nociception have rarely been studied. In
      the present report, we used c-Fos as a neuronal marker to analyze spatial and
      temporal patterns of pain-related neuronal activities within the S1 area of rats
      subjecting to subcutaneous (s.c.) injection of bee venom (BV) solution, a well
      established animal model of persistent pain. In naive and saline-treated rats, c
      Fos-labeled neurons were diffusely and sparsely distributed in the hindlimb
      region of S1 area. Following s.c. BV injection, c-Fos-labeled neurons became
      densely increased in superficial layers (II-III) and less increased in deep
      layers (IV-VI). The mean number of c-Fos positive neurons in the layers II-III
      began to increase at 1h and reached a peak at 2h after BV treatment that was
      followed by a gradual decrease afterward. The time course of c-Fos expression in
      the layers IV-VI was in parallel with that of the superficial layers, but with a
      much lower density and magnitude. The present results demonstrated that BV
      induced peripheral persistent nociception could evoke increased neuronal
      activities in the S1 area with predominant localization in layers II-III.

PMID- 18805460
TI  - Neural correlates of pre-performance routines in expert and novice archers.
AB  - The objective of the present study was to determine differences in neural
      networks between expert and novice archers during an archery pre-performance
      routine period (PPR). The experiment was conducted with eight world-class
      competitor or Olympic medalist archers and eight novices. In the experiment, the
      task was to shoot (by clicking a mouse with the right hand) if an archery target
      appeared on an LCD embedded in an functional magnetic resonance imaging (fMRI)
      scanner. The resultant fMRI data showed that when the experts were aiming, the
      occipital gyrus and temporal gyrus were activated, but when the novices were
      aiming, the frontal area was mainly activated. In addition, the anterior
      cingulate and posterior cingulate gyrus of the limbic lobe were also activated in
      the expert and novice groups, respectively. Our results demonstrated that expert
      and novice archers differed in levels of brain activation during the PPR period
      of a simulated archery task.

PMID- 18805461
TI  - Inflammation and susceptibility to neurodegeneration: the use of unbiased
      genetics to decipher critical regulatory pathways.
AB  - Neurodegeneration and signs of immune activation, with T cell infiltration, major
      histocompatibility complex class II expression and glial activation, occur in
      many neurological diseases. Although particular qualities of the inflammatory
      response have been proposed to be of importance, still very little is known about
      the exact factors that determine susceptibility to neurodegeneration. Mechanistic
      studies have yielded conflicting results, where inflammation is suggested both to
      attenuate and aggravate loss of nerve cells depending on the circumstances. In
      this context experimental genetic dissection in relevant rodent models such as
      experimental autoimmune encephalomyelitis and mechanical nerve injury can be a
      valuable tool to identify important genes/molecules/pathways. We here review
      emerging evidence using this approach that indicates different pathways related
      both to adaptive and local innate immune responses, which determine strain
      specific susceptibility to neuroimmune inflammation and neurodegeneration. Exact
      positioning of genes in these types of complex traits will be important for the
      understanding of pathogenetic mechanisms and to direct the focus of functional
      studies using classical experimental tools. Ultimately, a better knowledge about
      the interplay between the nervous system and the local and systemic immune system
      can define new ways of intervention in neurodegenerative processes.

PMID- 18805462
TI  - Cognitive development in macaques: attentional set-shifting in juvenile and adult
      rhesus monkeys.
AB  - In humans and nonhuman primates, the structure and function of frontal cortical
      regions of the brain are not completely developed until early adulthood. How this
      cortical development affects cognitive function continues to be elucidated. To
      that end, this experiment tested the ability of juvenile and adult rhesus monkeys
      to perform a cognitive task that is dependent upon intact frontal cortical
      function for optimal performance. Twenty-four juvenile (mean age 2.3 years) and
      16 adult (mean age 10.3 years) rhesus monkeys were tested on the Cambridge
      Neuropsychological Test Automated Battery intradimensional/extradimensional set
      shifting (ID/ED) task. Performance on the ID/ED task has been shown to be
      dependent upon frontal cortical function in both humans and nonhuman primates.
      Compared with adults, juveniles were impaired on the reversal of simple
      discrimination, intradimensional shift, reversal of intradimensional shift, and
      the extradimensional shift stages of the task. These results indicate juveniles
      committed more perseverative errors and more errors on the set-formation and set
      shifting components of the ID/ED task. The developmental stage of the juvenile
      monkeys corresponds to roughly 5 to 6-year-old children, and these results are
      consistent with performance of human children and adults on similar ID/ED tests
      and on several other tests of attentional set-shifting or attentional
      flexibility. Furthermore, these results are consistent with the ongoing
      development of frontal cortical structures relating to ongoing cognitive
      development in nonhuman primates.

PMID- 18805463
TI  - Chronic benzodiazepine-induced reduction in GABA(A) receptor-mediated synaptic
      currents in hippocampal CA1 pyramidal neurons prevented by prior nimodipine
      injection.
AB  - One week oral flurazepam (FZP) administration in rats results in reduced GABA(A)
      receptor-mediated synaptic transmission in CA1 pyramidal neurons associated with
      benzodiazepine tolerance in vivo and in vitro. Since voltage-gated calcium
      channel (VGCC) current density is enhanced twofold during chronic FZP treatment,
      the role of L-type VGCCs in regulating benzodiazepine-induced changes in CA1
      neuron GABA(A) receptor-mediated function was evaluated. Nimodipine (10 mg/kg,
      i.p.) or vehicle (0.5% Tween 80, 2 ml/kg) was injected 1 day after ending FZP
      treatment and 24 h prior to hippocampal slice preparation for measurement of
      mIPSC characteristics and in vitro tolerance to zolpidem. The reduction in
      GABA(A) receptor-mediated mIPSC amplitude and estimated unitary channel
      conductance measured 2 days after drug removal was no longer observed following
      prior nimodipine injection. However, the single nimodipine injection failed to
      prevent in vitro tolerance to zolpidem's ability to prolong mIPSC decay in FZP
      treated neurons, suggesting multiple mechanisms may be involved in regulating
      GABA(A) receptor-mediated synaptic transmission following chronic FZP
      administration. As reported previously in recombinant receptors, nimodipine
      inhibited synaptic GABA(A) receptor currents only at high concentrations (>30
      muM), significantly greater than attained in vivo (1 muM) 45 min after a single
      antagonist injection. Thus, the effects of nimodipine were unlikely to be related
      to direct effects on GABA(A) receptors. As with nimodipine injection, buffering
      intracellular free [Ca(2+)] with BAPTA similarly prevented the effects on GABA(A)
      receptor-mediated synaptic transmission, suggesting intracellular Ca(2+)
      homeostasis is important to maintain GABA(A) receptor function. The findings
      further support a role for activation of L-type VGCCs, and perhaps other Ca(2+)
      mediated signaling pathways, in the modulation of GABA(A) receptor synaptic
      function following chronic benzodiazepine administration, independent of
      modulation of the allosteric interactions between benzodiazepine and GABA binding
      sites.

PMID- 18805464
TI  - The role of cholinergic basal forebrain neurons in adenosine-mediated homeostatic
      control of sleep: lessons from 192 IgG-saporin lesions.
AB  - A topic of high current interest and controversy is the basis of the homeostatic
      sleep response, the increase in non-rapid-eye-movement (NREM) sleep and NREM
      delta activity following sleep deprivation (SD). Adenosine, which accumulates in
      the cholinergic basal forebrain (BF) during SD, has been proposed as one of the
      important homeostatic sleep factors. It is suggested that sleep-inducing effects
      of adenosine are mediated by inhibiting the wake-active neurons of the BF,
      including cholinergic neurons. Here we examined the association between SD
      induced adenosine release, the homeostatic sleep response and the survival of
      cholinergic neurons in the BF after injections of the immunotoxin 192
      immunoglobulin G (IgG)-saporin (saporin) in rats. We correlated SD-induced
      adenosine level in the BF and the homeostatic sleep response with the cholinergic
      cell loss 2 weeks after local saporin injections into the BF, as well as 2 and 3
      weeks after i.c.v. saporin injections. Two weeks after local saporin injection
      there was an 88% cholinergic cell loss, coupled with nearly complete abolition of
      the SD-induced adenosine increase in the BF, the homeostatic sleep response, and
      the sleep-inducing effects of BF adenosine infusion. Two weeks after i.c.v.
      saporin injection there was a 59% cholinergic cell loss, correlated with
      significant increase in SD-induced adenosine level in the BF and an intact sleep
      response. Three weeks after i.c.v. saporin injection there was an 87% cholinergic
      cell loss, nearly complete abolition of the SD-induced adenosine increase in the
      BF and the homeostatic response, implying that the time course of i.c.v. saporin
      lesions is a key variable in interpreting experimental results. Taken together,
      these results strongly suggest that cholinergic neurons in the BF are important
      for the SD-induced increase in adenosine as well as for its sleep-inducing
      effects and play a major, although not exclusive, role in sleep homeostasis.

PMID- 18805465
TI  - Extensive early motor and non-motor behavioral deficits are followed by striatal
      neuronal loss in knock-in Huntington's disease mice.
AB  - Huntington's disease is a neurodegenerative disorder, caused by an elongation of
      CAG repeats in the huntingtin gene. Mice with an insertion of an expanded
      polyglutamine repeat in the mouse huntingtin gene (knock-in mice) most closely
      model the disease because the mutation is expressed in the proper genomic and
      protein context. However, few knock-in mouse lines have been extensively
      characterized and available data suggest marked differences in the extent and
      time course of their behavioral and pathological phenotype. We have previously
      described behavioral anomalies in the open field as early as 1 month of age,
      followed by the appearance at 2 months of progressive huntingtin neuropathology,
      in a mouse carrying a portion of human exon 1 with approximately 140 CAG repeats
      inserted into the mouse huntingtin gene. Here we extend these observations by
      showing that early behavioral anomalies exist in a wide range of motor (climbing,
      vertical pole, rotarod, and running wheel performance) and non-motor functions
      (fear conditioning and anxiety) starting at 1-4 months of age, and are followed
      by progressive gliosis and decrease in dopamine and cyclic AMP-regulated
      phosphoprotein with molecular weight 32 kDa (DARPP32) (12 months) and a loss of
      striatal neurons at 2 years. At this age, mice also present striking spontaneous
      behavioral deficits in their home cage. The data show that this line of knock-in
      mice reproduces canonical characteristics of Huntington's disease, preceded by
      deficits which may correspond to the protracted pre-manifest phase of the disease
      in humans. Accordingly, they provide a useful model to elucidate early mechanisms
      of pathophysiology and the progression to overt neurodegeneration.

PMID- 18805466
TI  - Purinergic receptor immunoreactivity in the rostral ventromedial medulla.
AB  - The rostral ventromedial medulla (RVM) has long been recognized to play a pivotal
      role in nociceptive modulation. Pro-nociception within the RVM is associated with
      a distinct functional class of neurons, ON-cells that begin to discharge
      immediately before nocifensive reflexes. Anti-nociceptive function within the
      RVM, including the analgesic response to opiates, is associated with another
      distinct class, OFF-cells, which pause immediately prior to nocifensive reflexes.
      A third class of RVM neurons, NEUTRAL-cells, does not alter firing in association
      with nocifensive reflexes. ON-, OFF- and NEUTRAL-cells show differential
      responsiveness to various behaviorally relevant neuromodulators, including
      purinergic ligands. Iontophoresis of semi-selective P2X ligands, which are
      associated with nociceptive transmission in the spinal cord and dorsal root
      ganglia, preferentially activate ON-cells. By contrast, P2Y ligands activate OFF
      cells and P1 ligands suppress the firing of NEUTRAL cells. The current study
      investigates the distribution of P2X, P2Y and P1 receptor immunoreactivity in RVM
      neurons of Sprague-Dawley rats. Co-localization with tryptophan hydroxylase
      (TPH), a well-established marker for serotonergic neurons was also studied.
      Immunoreactivity for the four purinergic receptor subtypes examined was abundant
      in all anatomical subdivisions of the RVM. By contrast, TPH-immunoreactivity was
      restricted to a relatively small subset of RVM neurons concentrated in the
      nucleus raphe magnus and pallidus, as expected. There was a significant degree of
      co-localization of each purinergic receptor subtype with TPH-immunoreactivity.
      This co-localization was most pronounced for P2Y1 receptor immunoreactivity,
      although this was the least abundant among the different purinergic receptor
      subtypes examined. Immunoreactivity for multiple purinergic receptor subtypes was
      often co-localized in single neurons. These results confirm the physiological
      finding that purinergic receptors are widely expressed in the RVM. Purinergic
      neurotransmission in this region may play an important role in nociception and/or
      nociceptive modulation, as at other levels of the neuraxis.

PMID- 18805467
TI  - A quantitative assessment of glutamate uptake into hippocampal synaptic terminals
      and astrocytes: new insights into a neuronal role for excitatory amino acid
      transporter 2 (EAAT2).
AB  - The relative distribution of the excitatory amino acid transporter 2 (EAAT2)
      between synaptic terminals and astroglia, and the importance of EAAT2 for the
      uptake into terminals is still unresolved. Here we have used antibodies to
      glutaraldehyde-fixed d-aspartate to identify electron microscopically the sites
      of d-aspartate accumulation in hippocampal slices. About 3/4 of all terminals in
      the stratum radiatum CA1 accumulated d-aspartate-immunoreactivity by an active
      dihydrokainate-sensitive mechanism which was absent in EAAT2 glutamate
      transporter knockout mice. These terminals were responsible for more than half of
      all d-aspartate uptake of external substrate in the slices. This is unexpected as
      EAAT2-immunoreactivity observed in intact brain tissue is mainly associated with
      astroglia. However, when examining synaptosomes and slice preparations where the
      extracellular space is larger than in perfusion fixed tissue, it was confirmed
      that most EAAT2 is in astroglia (about 80%). Neither d-aspartate uptake nor EAAT2
      protein was detected in dendritic spines. About 6% of the EAAT2-immunoreactivity
      was detected in the plasma membrane of synaptic terminals (both within and
      outside of the synaptic cleft). Most of the remaining immunoreactivity (8%) was
      found in axons where it was distributed in a plasma membrane surface area several
      times larger than that of astroglia. This explains why the densities of neuronal
      EAAT2 are low despite high levels of mRNA in CA3 pyramidal cell bodies, but not
      why EAAT2 in terminals account for more than half of the uptake of exogenous
      substrate by hippocampal slice preparations. This and the relative amount of
      terminal versus glial uptake in the intact brain remain to be discovered.

PMID- 18805469
TI  - Alternative spliced variants in the pantetheinase family of genes expressed in
      human neutrophils.
AB  - Pantetheinase (EC 3.5.1.92) is an enzyme that hydrolyzes pantetheine, an
      intermediate metabolite of coenzyme A, into pantothenic acid (vitamin B(5)) and
      cysteamine, a potent antioxidant. The pantetheinase gene family consists of three
      independent genes, pantetheinase/vanin-1/VNN1, GPI-80/VNN2 and vanin-3/VNN3 that
      are each composed of seven exons. We herein report that human neutrophils express
      transcripts encoding at least nine splice variants of VNN3 and four splice
      variants of GPI-80/VNN2. Analysis of the DNA sequence of the human VNN3 gene
      demonstrated that the VNN3 locus in the human genome as well as the sequence of
      cDNA clones obtained in this study does not encode the complete VNN3 protein, as
      previously reported due to a frame shift caused by lack of one nucleotide.
      Moreover, the VNN3 locus indeed encodes smaller peptides compared to the proteins
      encoded by the mouse orthologous gene, vanin-3. The anti-GPI-80 monoclonal
      antibody 3H9 recognized amino acids 120-179 of the GPI-80/VNN2 protein as shown
      by the results of immunoblotting with recombinant GPI-80/VNN2 variant proteins.
      Immunoblotting with human neutrophil lysate suggests that the GPI-80/VNN2
      variants exist in human neutrophils. The existence of splice variants in the
      pantetheinase gene family suggests the possibility of alternative roles in
      addition to canonical enzymatic activity in human neutrophils.

PMID- 18805468
TI  - The thalamostriatal systems: anatomical and functional organization in normal and
      parkinsonian states.
AB  - Although we have gained significant knowledge in the anatomy and microcircuitry
      of the thalamostriatal system over the last decades, the exact function(s) of
      these complex networks remain(s) poorly understood. It is now clear that the
      thalamostriatal system is not a unique entity, but consists of multiple neural
      systems that originate from a wide variety of thalamic nuclei and terminate in
      functionally segregated striatal territories. The primary source of
      thalamostriatal projections is the caudal intralaminar nuclear group which, in
      primates, comprises the centromedian and parafascicular nuclei (CM/Pf). These two
      nuclei provide massive, functionally organized glutamatergic inputs to the whole
      striatal complex. There are several anatomical and physiological features that
      distinguish this system from other thalamostriatal projections. Although all
      glutamatergic thalamostriatal neurons express vGluT2 and release glutamate as
      neurotransmitter, CM/Pf neurons target preferentially the dendritic shafts of
      striatal projection neurons, whereas all other thalamic inputs are almost
      exclusively confined to the head of dendritic spines. This anatomic arrangement
      suggests that transmission of input from sources other than CM/Pf to the striatal
      neurons is likely regulated by dopaminergic afferents in the same manner as
      cortical inputs, while the CM/Pf axo-dendritic synapses do not display any
      particular relationships with dopaminergic terminals. A better understanding of
      the role of these systems in the functional circuitry of the basal ganglia relies
      on future research of the physiology and pathophysiology of these networks in
      normal and pathological basal ganglia conditions. Although much remains to be
      known about the role of these systems, recent electrophysiological studies from
      awake monkeys have provided convincing evidence that the CM/Pf-striatal system is
      the entrance for attention-related stimuli to the basal ganglia circuits.
      However, the processing and transmission of this information likely involves
      intrinsic GABAergic and cholinergic striatal networks, thereby setting the stage
      for complex physiological responses of striatal output neurons to CM/Pf
      activation. Finally, another exciting development that will surely generate
      significant interest towards the thalamostriatal systems in years to come is the
      possibility that CM/Pf may be a potential surgical target for movement disorders,
      most particularly Tourette syndrome and Parkinson's disease. Although the
      available clinical evidence is encouraging, these procedures remain empirical at
      this stage because of the limited understanding of the thalamostriatal systems.

PMID- 18805470
TI  - The assessment of the contribution of hair to methyl mercury excretion.
AB  - Due to its ability to avidly accumulate methyl mercury from blood, scalp hair has
      been widely used as a biological monitor for human exposure. The question arises
      that hair may also be an important route of elimination of methyl mercury from
      the body. Taking original publications and reviews on the physiology of hair
      (including growth by weigh and density) and on the deposition parameters for
      methyl mercury in the body (including the hair to blood concentration ratio of
      methyl mercury), one can calculate the rate of elimination of methyl mercury in
      hair. The result indicates that hair accounts for only a small fraction, less
      than 10%, of the total elimination of methyl mercury from the body. This
      relationship is expected to be maintained at every level when the dominant form
      of mercury is methyl. Other species of mercury I eliminated by hair even at a
      lower rate.

PMID- 18805471
TI  - Regucalcin down-regulation in rat kidney tissue after treatment with
      nephrotoxicants.
AB  - Gene expression of regucalcin (Rgn), a calcium-binding protein, was investigated
      in kidney of male Wistar rats treated with proximal tubule segment-specific
      nephrotoxicants, namely hexachloro-1:3-butadiene (HCBD), specific for S(3)
      segment (pars recta) and potassium dichromate (chromate) specific for S(1)-S(2)
      segments (pars convoluta), according to age of animals and dose of chemicals. In
      the age-dependent study, male Wistar rats were treated with a single injection of
      HCBD (100mg/kg b.w. i.p.) or chromate (25 mg/kg b.w. s.c.) at 5 weeks or 12 weeks
      of age; in dose-response study, rats were treated with a single injection of
      three doses of HCBD (25, 50, and 100 mg/kg b.w. i.p.) or chromate (8, 12.5, and
      25mg/kg b.w. s.c.) at 8 weeks of age. Forty-eight hours after treatment, Rgn and
      glutamine synthetase (GS) activity in kidney cortex, blood urea nitrogen (BUN)
      and plasma creatinine were measured; light microscopy was performed also. The
      results show that young rats are less susceptible to chromate (severe necrosis is
      evident only in adult rats), whereas age does not influence HCBD nephrotoxicity.
      Rgn is down regulated by HCBD at both age points, but not by chromate at 5 weeks
      of age. In addition, HCBD causes down-regulation of Rgn from the low dose in 8
      week-old rats, whereas chromate causes the same effect at the high dose only. GS
      activity in kidney cortex shows a similar behavior, even if sensitive to low
      doses of chromate also, whereas BUN and creatinine increase after the high dose
      of both chemicals only. Accordingly, light microscopy shows a segment-specific,
      dose-dependent increase of severity of damage caused by the chemicals. Rgn gene
      expression appears a sensitive genomic marker to evaluate the renal impairment
      caused by chemicals and its down-regulation seems to be related to damage, early
      or already established, to S(3) segment of the proximal tubule.

PMID- 18805473
TI  - Antitumoral and antiangiogenic activity of Synadenium umbellatum Pax.
AB  - AIM OF THE STUDY: Synadenium umbellatum Pax (SU), a plant used in the Midwestern
      region of Brazil, was tested for its antitumor and antiangiogenic activities in
      vitro, using K-562 and Ehrlich ascites tumor (EAT) cells, and in vivo, using the
      EAT-bearing model. MATERIALS AND METHODS: The viability of tumor cells was
      evaluated by MTT and trypan blue exclusion assays, after incubation with the
      ethanolic extract of SU (EESU) (0.15-20mg/mL) or equivalent concentrations of its
      partitioned fractions (chloroformic, hexanic, and methanolic). In vivo studies
      were performed in EAT-bearing mice treated intraperitoneally with 5, 10, and
      25mg/kg of the EESU or equivalent doses of the fractions for 10 days. The
      methotrexate (1.5mg/kg), for 10 days, was used as control. RESULTS: SU and
      fractions, except the methanolic, decreased the viability of the cells in a
      concentration-dependent manner. In vivo results showed a significant dose
      dependent antitumoral efficacy of SU against EAT growth. The best results in
      prolonging life span were produced by 25mg/kg of EESU. In these animals, the
      levels of vascular endothelial growth factor were markedly decreased after the
      treatment. CONCLUSIONS: The data presented herein could open interesting
      perspectives for further research of SU as a candidate anticancer agent.

PMID- 18805472
TI  - Micro-scale devices for transdermal drug delivery.
AB  - Skin makes an excellent site for drug and vaccine delivery due to easy
      accessibility, immuno-surveillance functions, avoidance of macromolecular
      degradation in the gastrointestinal tract and possibility of self-administration.
      However, macromolecular drug delivery across the skin is primarily accomplished
      using hypodermic needles, which have several disadvantages including accidental
      needle-sticks, pain and needle phobia. These limitations have led to extensive
      research and development of alternative methods for drug and vaccine delivery
      across the skin. This review focuses on the recent trends and developments in
      this field of micro-scale devices for transdermal macromolecular delivery. These
      include liquid jet injectors, powder injectors, microneedles and thermal
      microablation. The historical perspective, mechanisms of action, important design
      parameters, applications and challenges are discussed for each method.

PMID- 18805474
TI  - The biological activity and chemistry of the southern African Combretaceae.
AB  - AIM OF THE STUDY: Members of the Combretaceae family are widely traded in the
      traditional medicine market in southern Africa. The family is also used for
      medicinal purposes in the rest of Africa and Asia for close to 90 medicinal
      indications. Many of these indications are related to treating infections. This
      contribution summarizes work done to date and identifies avenues for future
      research. MATERIALS AND METHODS: Substantial work has already been done on the
      chemistry of especially Combretum and Terminalia species over many years. During
      the last decade we have focussed on bio-assay guided isolation of biologically
      active compounds with the aim of producing new effective antimicrobial products.
      RESULTS AND DISCUSSION: Methods developed to facilitate this process and data on
      25 compounds isolated from 7 species are presented. The large majority of
      compounds isolated were known, but the biological activities were not known. In
      practically all cases the antibacterial or antifungal activity of compounds
      isolated were much lower than expected from the activity of the crude extracts.
      It appears that synergism plays a role in antimicrobial activity of plant
      extracts and that the hope of isolating a single compound that can be used as a
      new agent to address antibiotic resistance has been frustrated. By simple
      manipulation such as selective extraction the activity of some crude extracts
      could however, be increased substantially and this offers a new approach to
      address antibiotic resistance via the herbal medicine industry. Practically all
      extracts obtained using intermediate polarity extractants had reasonable to very
      good activity with MICs as low as 40 microg/ml, validating the traditional use
      for infectious diseases. Aqueous extracts however, generally had hardly any
      activity. CONCLUSIONS: The Combretaceae contains a diversity of antimicrobial
      compounds. Because poor people usually have only water available as extractant,
      it raises the question how plants growing in poor rural communities can be used
      to treat infections more effectively, and what the mechanism of activity of
      aqueous extracts used to treat infections in traditional medicine are.

PMID- 18805475
TI  - The potential of South African plants against Mycobacterium infections.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: In South Africa, tuberculosis (TB) caused by
      Mycobacterium tuberculosis is the most commonly notified disease and the fifth
      largest cause of mortality, with one in ten cases of TB resistant to treatment in
      some areas. Many plants are used locally in traditional medicine to treat TB
      related symptoms. AIM OF THE STUDY: The aim was to summarize currently available
      knowledge on South African plants used to treat TB symptoms, and
      antimycobacterial efficacy of plant-derived extracts and compounds. MATERIALS AND
      METHODS: The traditional uses of plants for respiratory ailments and TB were
      collated and tabulated. The antimycobacterial activity tests of extracts and
      chemical constituents of several of these plants and others using different
      methods and target organisms were summarized. RESULTS: Almost 180 plants used for
      TB-related symptoms in South African traditional medicine were documented. About
      30% of these have been tested for antimycobacterial efficacy, mostly against fast
      growing, non-pathogenic Mycobacterium species. CONCLUSIONS: Many plant species
      are used in traditional South African medicine to alleviate symptoms of TB, and
      several interesting leads have originated for further inquiry following in vitro
      antimycobacterial activity evaluation. However, much work remains to be done on
      the systematic assessment of anti-TB efficacy of local plants against pathogenic
      Mycobacterium species, both in vitro and in vivo.

PMID- 18805476
TI  - In vivo imaging markers of neurodegeneration of the substantia nigra.
AB  - Non invasive detection and monitoring of substantia nigra degeneration is a long
      sought aim for neuroscientists, clinicians and pharmaceutical companies with an
      interest in Parkinson's disease (PD). Functional imaging techniques are
      established tools to assess the extent of striatal dopaminergic denervation that
      indirectly reflects nigral degeneration. They allow characterization of the
      dopaminergic denervation during the premotor phase of PD and have clinical value
      to establish the diagnosis in parkinsonism, but have proven to be unsatisfactory
      as surrogate markers in recent treatment trials. There is strong research
      interest in developing new imaging tests for nigral degeneration using a variety
      of structural brain imaging techniques. Nigral hyperechogenicity assessed by
      transcranial sonography emerges as a robust and low cost test to diagnose PD.
      Additionally, various advanced magnetic resonance imaging contrasts and high
      field magnetic resonance spectroscopy show promising sensitivity to nigral
      pathology in PD. Qualification of these emerging imaging tests against defined
      biomarker criteria is a complex and challenging task ahead. More systematic
      validation studies analogous to clinical trials are needed to meet the
      expectations and criteria defined by regulatory bodies before imaging biomarkers
      can be used as surrogate endpoints for neuroprotective or restorative trials.

PMID- 18805477
TI  - The effects of nanoparticles on mouse testis Leydig cells in vitro.
AB  - We have indicated the possibility that nanoparticles such as diesel exhaust
      particles (DEP) and titanium dioxide (TiO(2)) may impair the male mouse
      reproductive system. In this study, to evaluate the direct effect of
      nanoparticles on testis-constituent cells, we examined the effect of DEP, TiO(2)
      and carbon black (CB) on mouse Leydig TM3 cells, the testosterone-producing cells
      of the testis. The uptake of three nanoparticles into Leydig cells was detected
      using transmission electron microscopy (TEM) or field emission type scanning
      electron microscopy/energy-dispersive X-ray spectroscopy (FE-SEM/EDS). We
      examined the cytotoxicity and the effect on gene expression by treatment with
      nanoparticles. TiO(2) was more cytotoxic to Leydig cells than other
      nanoparticles. The proliferation of Leydig cells was suppressed transiently by
      treatment with TiO(2) or DEP. The expression of heme oxygenase-1 (HO-1), a
      sensitive marker for oxidative stress, was induced remarkably by treatment with
      DEP. Furthermore, CB and DEP slightly increased the gene expression of the
      steroidogenic acute regulatory (StAR) protein, the factor that controls
      mitochondrial cholesterol transfer. In this study, we found that DEPs, TiO(2) and
      CB nanoparticles were taken up by Leydig cells, and affected the viability,
      proliferation and gene expression. The patterns were unique for each
      nanoparticle.

PMID- 18805478
TI  - Anti-free radical activities of kaempferol isolated from Acacia nilotica (L.)
      Willd. Ex. Del.
AB  - In the present study the polyphenolic compound has been isolated from methanol
      extract of Acacia nilotica Willd. Ex. Del. which has been identified as
      kaempferol (AN-5) by NMR and mass spectroscopy. The antioxidant potential of the
      AN-5 was demonstrated in several in vitro assays: measuring the proton radical
      scavenging activity (DPPH scavenging assay), hydroxyl radical scavenging activity
      (deoxyribose degradation assay), metal chelating activity, reducing power and
      inhibition of lipid peroxidation. It was found that the effect of the compound AN
      5 was strongly dose dependent up to the concentrations 1-50 microg/ml in DPPH
      assay and 1-100 microg/ml in deoxyribose degradation assay but did not show
      further change above the highest concentrations.

PMID- 18805479
TI  - Constriction of pulmonary artery by peroxide: role of Ca2+ release and PKC.
AB  - Reactive oxygen species are implicated in pulmonary hypertension and hypoxic
      pulmonary vasoconstriction. We examined the effects of low concentrations of
      peroxide on intrapulmonary arteries (IPA). IPAs from Wistar rats were mounted on
      a myograph for recording tension and estimating intracellular Ca2+ using Fura
      PE3. Ca2+ sensitization was examined in alpha-toxin-permeabilized IPAs, and
      phosphorylation of MYPT-1 and MLC(20) was assayed by Western blot. Peroxide (30
      microM) induced a vasoconstriction with transient and sustained components and
      equivalent elevations of intracellular Ca2+. The transient constriction was
      strongly suppressed by indomethacin, the TP-receptor antagonist SQ-29584, and the
      Rho kinase inhibitor Y-27632, whereas sustained constriction was unaffected.
      Neither vasoconstriction nor elevation of intracellular Ca2+ was affected by
      removal of extracellular Ca2+, whereas dantrolene suppressed the former and
      ryanodine abolished the latter. Peroxide-induced constriction of permeabilized
      IPAs was unaffected by Y-27632 but abolished by PKC inhibitors; these also
      suppressed constriction in intact IPAs. Peroxide caused translocation of
      PKCalpha, but had no significant effect on MYPT-1 or MLC(20) phosphorylation. We
      conclude that in IPAs peroxide causes transient release of vasoconstrictor
      prostanoids, but sustained constriction is associated with release of Ca2+ from
      ryanodine-sensitive stores and a PKC-dependent but Rho kinase- and MLC(20)
      independent constrictor mechanism.

PMID- 18805480
TI  - Redox modulation inhibits CD8 T cell effector function.
AB  - The evolutionary preservation of reactive oxygen species in innate immunity
      underscores the important roles these constituents play in immune cell activity
      and as signaling intermediates. In an effort to exploit these pathways to achieve
      control of aberrant immune activation we demonstrate that modulation of redox
      status suppresses cell proliferation and production of IL-2, IFN-gamma, TNF
      alpha, and IL-17 in two robust CD8 T-cell-dependent in vitro mouse models: (1)
      response to alloantigen in an mixed leukocyte reaction and (2) CD8 T cell
      receptor transgenic OT-1 response to cognate peptide (SIINFEKL). To correlate
      these findings with cytotoxic lymphocyte (CTL) function we performed cytotoxicity
      assays and found that redox modulation diminishes the ability of alloantigen
      specific and antigen-specific OT-1 CTLs to kill their corresponding antigen
      expressing target cells. To further examine the mechanisms of redox-mediated
      repression of CTL target cell lysis, we analyzed the expression of the effector
      molecules IFN-gamma, perforin, and granzyme B and the degranulation marker CD107a
      (LAMP-1). In both models, redox modulation reduced the expression of these
      effector components by at least fivefold. These results demonstrate that redox
      modulation quells the CD8 T cell response to alloantigen and the T cell receptor
      transgenic CD8 T cell response to its cognate antigen by inhibiting
      proliferation, proinflammatory cytokine synthesis, and CTL effector mechanisms.

PMID- 18805481
TI  - 4-Hydroxynonenal enhances MMP-2 production in vascular smooth muscle cells via
      mitochondrial ROS-mediated activation of the Akt/NF-kappaB signaling pathways.
AB  - 4-Hydroxynonenal (HNE) accumulates at atherosclerotic lesions, but its role in
      the progression of atherosclerosis is not clear. Considering the role of matrix
      metalloproteinases (MMP) in plaque destabilization, we investigated the mechanism
      by which HNE induces MMP production in vascular smooth muscle cells (VSMC). VSMC
      stimulated by HNE (1.0 microM) produced enzymatically active MMP-2 with an
      increased promoter activity, which was abolished by mutation of the NF-kappaB
      binding site in the promoter region. The increased NF-kappaB activity with
      subsequent MMP-2 production by HNE was significantly attenuated by transfection
      with Akt siRNA as well as by pretreatment with the PI3K/Akt inhibitors LY294002
      (10 microM) and SH-5 (1.0 microM). The phosphorylation of Akt occurred as early
      as 5 min in VSMC exposed to HNE and was markedly attenuated by inhibition of
      mitochondrial reactive oxygen species (ROS). Furthermore, the impact of
      mitochondrial ROS on HNE-induced Akt phosphorylation with subsequent MMP-2
      production was also demonstrated in mitochondrial function-deficient VSMC, as
      well as in cells transfected with manganese superoxide dismutase. Taken together,
      these results suggest that HNE enhances MMP-2 production in VSMC via
      mitochondrial ROS-mediated activation of the Akt/NF-kappaB signaling pathways.

PMID- 18805482
TI  - Mallory-Denk-bodies: lessons from keratin-containing hepatic inclusion bodies.
AB  - Inclusion bodies are characteristic morphological features of various neuronal,
      muscular and other human disorders. They share common molecular constituents such
      as p62, chaperones and proteasome subunits. The proteins within aggregates are
      misfolded with increased beta-sheet structure, they are heavily phosphorylated,
      ubiquitinylated and partially degraded. Furthermore, involvement of proteasomal
      system represents a common feature of virtually all inclusions. Multiple
      aggregates contain intermediate filament proteins as their major constituents.
      Among them, Mallory-Denk bodies (MDBs) are the best studied. MDBs represent
      hepatic inclusions observed in diverse chronic liver diseases such as alcoholic
      and non-alcoholic steatohepatitis, chronic cholestasis, metabolic disorders and
      hepatocellular neoplasms. MDBs are induced in mice fed griseofulvin or 3,5
      diethoxycarbonyl-1,4-dihydrocollidine and resolve after discontinuation of toxin
      administration. The availability of a drug-induced model makes MDBs a unique tool
      for studying inclusion formation. Our review summarizes the recent advances
      gained from this model and shows how they relate to observations in other
      aggregates. The MDB formation-underlying mechanisms include protein misfolding,
      chaperone alterations, disproportional protein expression with keratin 8>keratin
      18 levels and subsequent keratin 8 crosslinking via transglutaminase. p62
      presence is crucial for MDB formation. Proteasome inhibitors precipitate MDB
      formation, whereas stimulation of autophagy with rapamycin attenuates their
      formation.

PMID- 18805483
TI  - Immediate release pellets with lipid binders obtained by solvent-free cold
      extrusion.
AB  - Lipid-based drug delivery systems have spread in their use in pharmaceutical drug
      development. This work focuses on the use of lipid binders as alternative non
      toxic extrusion aid for pellet formulations. The preparation of immediate release
      pellets with solid lipid binders through a solvent-free cold
      extrusion/spheronisation process was investigated in this study. Various binary,
      ternary and quaternary mixtures of powdered lipids and the model drug sodium
      benzoate were investigated and compared to well-known wet extrusion binders like
      microcrystalline cellulose and kappa-carrageenan. The cold lipid extrusion
      process offers multiple advantages as it is suitable for thermal sensitive as
      well as for hygroscopic drugs, furthermore no drying process to evaporate the
      solvent is needed and the process is feasible for different extruder types. Some
      of the developed pellets showed favourable properties like spherical shape,
      narrow size distribution, a high drug load of 80% sodium benzoate and a drug
      release of more than 90% within 40 min. The stability of drug release, which can
      be problematic when using lipid excipients, was sufficient for some mixtures, as
      storage under elevated temperatures changed the release profiles only slightly
      and no formulation released less than 80% within the first 60 min. A formulation
      with a mixture of hard fat, glycerol distearate and glycerol trimyristate showed
      the best results, as pellets with a low aspect ratio, narrow size distribution
      and complete drug release were obtained. Using appropriate mixtures of
      acylglycerides it becomes possible to produce pharmaceutical pellets with
      immediate release characteristics by cold extrusion and subsequent
      spheronisation. Thus, lipids are very promising alternatives to commonly used
      extrusion/spheronisation binders.

PMID- 18805484
TI  - Transferrin- and transferrin-receptor-antibody-modified nanoparticles enable drug
      delivery across the blood-brain barrier (BBB).
AB  - Human serum albumin (HSA) nanoparticles were manufactured by desolvation.
      Transferrin or transferrin receptor monoclonal antibodies (OX26 or R17217) were
      covalently coupled to the HSA nanoparticles using the NHS-PEG-MAL-5000
      crosslinker. Loperamide was used as a model drug since it normally does not cross
      the blood-brain barrier (BBB) and was bound to the nanoparticles by adsorption.
      Loperamide-loaded HSA nanoparticles with covalently bound transferrin or the OX26
      or R17217 antibodies induced significant anti-nociceptive effects in the tail
      flick test in ICR (CD-1) mice after intravenous injection, demonstrating that
      transferrin or these antibodies covalently coupled to HSA nanoparticles are able
      to transport loperamide and possibly other drugs across the BBB. Control
      loperamide-loaded HSA nanoparticles with IgG2a antibodies yielded only marginal
      effects.

PMID- 18805485
TI  - Processing of complex sounds in the auditory system.
AB  - The coding of complex sounds in the early auditory system has a 'standard model'
      based on the known physiology of the cochlea and main brainstem pathways. This
      model accounts for a wide range of perceptual capabilities. It is generally
      accepted that high cortical areas encode abstract qualities such as spatial
      location or speech sound identity. Between the early and late auditory system,
      the role of primary auditory cortex (A1) is still debated. A1 is clearly much
      more than a 'whiteboard' of acoustic information-neurons in A1 have complex
      response properties, showing sensitivity to both low-level and high-level
      features of sounds.

PMID- 18805486
TI  - Emerging views of corticothalamic function.
AB  - Although it is now generally accepted that the thalamus is more than a simple
      relay of sensory signals to the cortex, we are just beginning to gain an
      understanding of how corticothalamic feedback influences sensory processing.
      Results from an increasing number of studies across sensory systems and different
      species reveal effects of feedback both on the receptive fields of thalamic
      neurons and on the transmission of sensory information between the thalamus and
      cortex. Importantly, these studies demonstrate that the cortico-thalamic
      projection cannot be viewed in isolation, but must be considered as an integral
      part of a thalamo-corticothalamic circuit which intimately interconnects the
      thalamus and cortex for sensory processing.

PMID- 18805487
TI  - Capillary blood sampling as an alternative to venipuncture in the assessment of
      serum 25 hydroxyvitamin D levels.
AB  - This study compared 25-hydroxyvitamin D [25(OH)D] measurements in capillary and
      venous blood samples collected, respectively by fingerprick and venipuncture.
      Capillary blood for measuring 25(OH)D has potential advantages by reducing blood
      volume required (2mL versus 0.3mL for venipuncture and capillary sampling,
      respectively), facilitating blood collection for those populations in whom
      venipuncture is difficult (e.g. infants and children), improving patient
      convenience and reducing costs associated with phlebotomy. The results
      demonstrated a highly significant relationship between 25(OH)D levels in serum
      derived from venous and capillary blood samples (r(2)=0.901). Despite
      statistically higher 25(OH)D levels in fingerprick samples (108+/-9nmol/L)
      compared with venipuncture samples (90+/-7nmol/L), the correlation between venous
      and capillary samples provides support for this approach as a practical
      alternative to venipuncture for vitamin D determination. However, clinical
      application may require the incorporation of a correction factor for the
      assessment of insufficiency, and research studies should avoid using the two
      methods interchangeably. Studying vitamin D's role in health and disease requires
      collection techniques and measurement methods that are reliable, reproducible,
      easily accessible, inexpensive and minimally burdensome to the patient. The
      option to collect patient samples by fingerprick may facilitate the collection
      process.

PMID- 18805488
TI  - Caspase inhibition attenuates accumulation of beta-amyloid by reducing beta
      secretase production and activity in rat brains after stroke.
AB  - In this study, we tested if caspase-3 inhibition decreased ischemia-induced Abeta
      elevation by reducing beta-secretase (BACE1) activity. Changes in caspase-3,
      Abeta and BACE1 levels were detected in rat striatum on different days after
      middle cerebral artery occlusion using immunostaining. We found that the positive
      labeled cells of activated caspase-3, Abeta, and BACE1 were significantly and
      time-dependently increased in the ipsilateral striatum. The results of Western
      blotting and RT-PCR showed that caspase-3 inhibitor Z-DEVD-FMK reduced BACE1 mRNA
      and protein levels, and inhibited its protease activity, thereby decreasing the
      amount of APP C99 and Abeta in ischemic brains. Moreover, Z-DEVD-FMK reduced
      BACE1 and GFAP double-labeled cells, but not GFAP protein levels or GFAP-labeled
      cells, in the ipsilateral striatum. Thus, we demonstrated that caspase-3
      inhibition attenuated ischemia-induced Abeta formation by reducing BACE1
      production and activity. This finding provides a therapeutic strategy for
      preventing Abeta accumulation and reducing the risk of neurodegeneration after
      stroke.

PMID- 18805489
TI  - Attenuation of apoptosis in vitro and ischemia/reperfusion injury in vivo in
      mouse skeletal muscle by P2Y6 receptor activation.
AB  - Activation of the G(q)-coupled P2Y(6) receptor heterologously expressed in
      astrocytes significantly attenuates apoptosis induced by tumor necrosis factor
      alpha (TNFalpha). We have extended the analysis of P2Y(6) receptor-induced
      cytoprotection to mouse skeletal muscle cells endogenously expressing this
      receptor. The endogenous P2Y(6) receptor agonist UDP and synthetic agonist
      MRS2693 protected C2C12 skeletal muscle cells against apoptosis in a
      concentration-dependent manner (0.1-10 nM) as determined by propidium iodide
      staining, histochemical analysis using hematoxylin and Hoechst 33258, and DNA
      fragmentation. The insurmountable P2Y(6) receptor antagonist MRS2578 blocked the
      protection. TNFalpha-induced apoptosis in C2C12 cells correlated with activation
      of the transcription factor NF-kappaB. The NF-kappaB activation was attenuated by
      10nM MRS2693, which activated the antiapoptic ERK1/2 pathway. In an in vivo mouse
      hindlimb model, MRS2693 protected against skeletal muscle ischemia/reperfusion
      injury. The P2Y(6) receptor is a novel cytoprotective receptor that deserves
      further exploration in ameliorating skeletal muscle injury.

PMID- 18805490
TI  - Expression, purification, and functional characterization of recombinant human
      interleukin-7.
AB  - Human interleukin-7 (IL-7) is a member of the interleukin family. Numerous
      studies have demonstrated IL-7's effect on B- and T-cell development as well as
      its potential in various clinical applications. Previously, a study reported that
      IL-7 could be purified from inclusion bodies using a prokaryotic system, however,
      the required refolding step limits the recovery rate. This study was designed to
      produce a bioactive recombinant human IL-7 (rhIL-7) in a eukaryotic expression
      system in order to obtain higher yields of the protein with simpler purification
      steps. We cloned human IL-7 cDNA and successfully expressed active recombinant
      protein in yeast using the Pichia pastoris expression system. A simple
      purification strategy was established to purify the rhIL-7 from the fermentation
      supernatant, yielding 35 mg/L at 95% purity by the use of a common SP Sepharose
      FF cation-exchange chromatography. Functional analysis of the purified rhIL-7 by
      the pre-B cell MTT (3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide)
      proliferation assay demonstrated a specific activity comparable to commercial
      sources. These results suggest that purification of rhIL-7 from yeast provides a
      sound strategy for large-scale production of the rhIL-7 for clinical applications
      as well as basic researches.

PMID- 18805491
TI  - Axial growth of hexactinellid spicules: formation of cone-like structural units
      in the giant basal spicules of the hexactinellid Monorhaphis.
AB  - The glass sponge Monorhaphis chuni (Porifera: Hexactinellida) forms the largest
      bio-silica structures on Earth; their giant basal spicules reach sizes of up to
      3m and diameters of 8.5mm. Previously, it had been shown that the thickness
      growth proceeds by appositional layering of individual lamellae; however, the
      mechanism for the longitudinal growth remained unstudied. Now we show, that the
      surface of the spicules have towards the tip serrated relief structures that are
      consistent in size and form with the protrusions on the surface of the spicules.
      These protrusions fit into the collagen net that surrounds the spicules. The
      widths of the individual lamellae do not show a pronounced size tendency. The
      apical elongation of the spicule proceeds by piling up cone-like structural units
      formed from silica. As a support of the assumption that in the extracellular
      space silicatein(-like) molecules exist that associate with the external surface
      of the respective spicule immunogold electron microscopic analyses were
      performed. With the primmorph system from Suberites domuncula we show that
      silicatein(-like) molecules assemble as string- and net-like arrangements around
      the spicules. At their tips the silicatein(-like) molecules are initially stacked
      and at a later stay also organized into net-like structures. Silicatein(-like)
      molecules have been extracted from the giant basal spicule of Monorhaphis.
      Applying the SDS-PAGE technique it could be shown that silicatein molecules
      associate to dimers and trimers. Higher complexes (filaments) are formed from
      silicatein(-like) molecules, as can be visualized by electron microscopy (SEM).
      In the presence of ortho-silicate these filaments become covered with 30-60nm
      long small rod-like/cuboid particles of silica. From these data we conclude that
      the apical elongation of the spicules of Monorhaphis proceeds by piling up cone
      like silica structural units, whose synthesis is mediated by silicatein(-like)
      molecules.

PMID- 18805492
TI  - Passive protection of shrimp against white spot syndrome virus (WSSV) using
      specific antibody from egg yolk of chickens immunized with inactivated virus or a
      WSSV-DNA vaccine.
AB  - White spot syndrome virus (WSSV) causes high mortality and large economic losses
      in cultured shrimp. The VP28, VP19 and VP15 genes encode viral structural
      proteins of WSSV. In this study, hens were immunized with recombinant plasmid
      (pCI-VP28/VP19/VP15) with linkers or with inactivated WSSV, which used CpG
      oligodeoxynucleotides (CpG ODNs) and Freund's adjuvant as adjuvant, respectively.
      Egg yolk immunoglobulin (IgY) from hens immunized with inactivated vaccine and
      DNA vaccine was obtained, purified and used for protection of Metapenaeus ensis
      shrimp against WSSV. The data showed that the antibody response of the hens
      immunized with the DNA vaccine was improved by CpG ODNs as adjuvant, but was
      still inferior to inactivated WSSV in both sera and egg yolks. Using specific IgY
      from hens immunized with inactivated WSSV and DNA vaccine to neutralize WSSV, the
      challenged shrimp showed 73.3% and 33.3% survival, respectively. Thus, the
      results suggest that passive immunization strategy with IgY will be a valuable
      method against WSSV infection in shrimp.

PMID- 18805493
TI  - Cluster mass inference via random field theory.
AB  - Cluster extent and voxel intensity are two widely used statistics in neuroimaging
      inference. Cluster extent is sensitive to spatially extended signals while voxel
      intensity is better for intense but focal signals. In order to leverage strength
      from both statistics, several nonparametric permutation methods have been
      proposed to combine the two methods. Simulation studies have shown that of the
      different cluster permutation methods, the cluster mass statistic is generally
      the best. However, to date, there is no parametric cluster mass inference
      available. In this paper, we propose a cluster mass inference method based on
      random field theory (RFT). We develop this method for Gaussian images, evaluate
      it on Gaussian and Gaussianized t-statistic images and investigate its
      statistical properties via simulation studies and real data. Simulation results
      show that the method is valid under the null hypothesis and demonstrate that it
      can be more powerful than the cluster extent inference method. Further, analyses
      with a single subject and a group fMRI dataset demonstrate better power than
      traditional cluster size inference, and good accuracy relative to a gold-standard
      permutation test.

PMID- 18805494
TI  - Cortical development in brown capuchin monkeys: a structural MRI study.
AB  - Relative to other primates, Cebus monkeys display unusually fast postnatal brain
      growth and motor skill development. The neonatal capuchin brain, at approximately
      29-34 g, is a smaller proportion of the adult brain weight (c. 50%) than is the
      brain of other primates except humans and great apes. Here we describe, from a
      cross-sectional sample, brain development in 29 brown capuchin monkeys (Cebus
      apella) using high-resolution structural magnetic resonance images, focusing on
      growth patterns in total brain volume, cortical gray and white matter volume,
      frontal lobe gray and white matter volume, and corpus callosum area. Non-linear
      age-related changes in total brain volume, cortical white matter volume and
      frontal white matter volume were detected from birth - 5 years. Sex differences
      in corpus callosum:brain ratio were also found, with males having a 10% smaller
      corpus callosum:brain ratio than females regardless of age. Female corpus
      callosum:brain ratio showed significant age-related related changes, whereas
      males did not display any significant changes across age. Sex differences were
      also found in cortical gray and frontal lobe gray matter volumes, with males
      having larger volumes than females. These findings support the conclusion that
      capuchins undergo rapid neurological change during the first few years of life.

PMID- 18805495
TI  - Hippocampal volume and cortical sources of EEG alpha rhythms in mild cognitive
      impairment and Alzheimer disease.
AB  - Atrophy of hippocampus and alteration of resting eyes-closed
      electroencephalographic (EEG) rhythms represent important features of mild
      cognitive impairment (MCI) and Alzheimer's disease (AD). Here we evaluated linear
      and non-linear aspects of the relationship between these features in the
      continuum along MCI and AD conditions, as a reflection of neurodegenerative
      processes. Eyes-closed resting EEG data were recorded in 60 healthy elderly
      (Nold), 88 MCI, and 35 Alzheimer's disease (AD) patients. Hippocampal volume was
      measured in magnetic resonance imaging of the MCI and AD subjects. Based on the
      normalized hippocampal volume, selected MCI subjects could be divided into two
      demographically paired sub-groups: those with larger hippocampal volume (MCI +h;
      N=40; mini mental state evaluation - MMSE - score=27.5+/-0.26 SE) and those with
      smaller hippocampal volume (MCI -h; N=40; h; MMSE=26.5+/-0.34 SE); the normalized
      hippocampal volume was statistically greater in the MCI +h than in the MCI -h and
      AD subjects (p<0.0001). EEG rhythms of interest were delta (2-4 Hz), theta (4-8
      Hz), alpha 1 (8-10.5 Hz), alpha 2 (10.5-13 Hz), beta 1 (13-20 Hz), and beta 2 (20
      30 Hz). Cortical EEG generators were estimated by LORETA software. Results showed
      that the power of occipital, parietal, and temporal alpha 1 sources was maximum
      in MCI +h, intermediate in MCI -h, and low in AD patients. Furthermore, the power
      of these sources was linearly and non-linearly correlated with the normalized
      hippocampal volume. These 3 EEG sources were given as input for evaluating
      correlations (linear, exponential, logarithmic and power) with hippocampal
      volume. When subjects were considered as a unique group, there was a significant
      linear correlation of hippocampal volume with the magnitude of alpha 1 sources in
      the parietal, occipital and temporal areas. In general, the EEG sources showing
      significant linear correlation with hippocampal volume also supported a non
      linear correlation with hippocampal volume strongly for the logarithmic one. The
      present results suggest that progressive atrophy of hippocampus correlates with
      decreased cortical alpha power, as estimated by using LORETA source modeling, in
      the continuum along MCI and AD conditions.

PMID- 18805496
TI  - Processing 3D form and 3D motion: respective contributions of attention-based and
      stimulus-driven activity.
AB  - This study aims at segregating the neural substrate for the 3D-form and 3D-motion
      attributes in structure-from-motion perception, and at disentangling the stimulus
      driven and endogenous-attention-driven processing of these attributes. Attention
      and stimulus were manipulated independently: participants had to detect the
      transitions of one attribute--form, 3D motion or colour--while the visual
      stimulus underwent successive transitions of all attributes. We compared the BOLD
      activity related to form and 3D motion in three conditions: stimulus-driven
      processing (unattended transitions), endogenous attentional selection (task) or
      both stimulus-driven processing and attentional selection (attended transitions).
      In all conditions, the form versus 3D-motion contrasts revealed a clear
      dorsal/ventral segregation. However, while the form-related activity is
      consistent with previously described shape-selective areas, the activity related
      to 3D motion does not encompass the usual "visual motion" areas, but rather
      corresponds to a high-level motion system, including IPL and STS areas. Second,
      we found a dissociation between the neural processing of unattended attributes
      and that involved in endogenous attentional selection. Areas selective for 3D
      motion and form showed either increased activity at transitions of these
      respective attributes or decreased activity when subjects' attention was directed
      to a competing attribute. We propose that both facilitatory and suppressive
      mechanisms of attribute selection are involved depending on the conditions
      driving this selection. Therefore, attentional selection is not limited to an
      increased activity in areas processing stimulus properties, and may unveil
      different functional localization from stimulus modulation.

PMID- 18805497
TI  - Deviation age of a deep-sea demersal fish, Bothrocara hollandi, between the Japan
      Sea and the Okhotsk Sea.

PMID- 18805498
TI  - Characterization of the atromentin biosynthesis genes and enzymes in the
      homobasidiomycete Tapinella panuoides.
AB  - This report highlights the first biochemical characterization of a multi-domain
      biosynthetic enzyme for basidiomycete secondary metabolism: the tri-domain enzyme
      atromentin synthetase AtrA, from Tapinella panuoides, which adenylates and
      dimerizes 4-hydroxyphenylpyruvic acid into atromentin. Also, the l-tyrosine:2
      oxoglutarate aminotransferase AtrD, which provides the substrate for this
      dimerization step, has been characterized. AtrA and AtrD expand the shikimic acid
      pathway from l-tyrosine to atromentin, the central terphenylquinone intermediate
      for a prominent and widely occurring class of basidiomycete pigments, among them
      various pharmaceutically relevant compounds. The genes atrA and atrD were cloned
      and found to be clustered within one genetic locus. Given the broad distribution
      of atromentin-derived compounds among homobasidiomycetes we expect our system
      represents a widely applicable model.

PMID- 18805499
TI  - Ecological factors affect the level and scaling of avian BMR.
AB  - The basal rate of metabolism (BMR) in 533 species of birds, when examined with
      ANCOVA, principally correlates with body mass, most of the residual variation
      correlating with food habits, climate, habitat, a volant or flightless condition,
      use or not of torpor, and a highland or lowland distribution. Avian BMR also
      correlates with migratory habits, if climate and a montane distribution is
      excluded from the analysis, and with an occurrence on small islands if a
      flightless condition and migration are excluded. Residual variation correlates
      with membership in avian orders and families principally because these groups are
      behaviorally and ecologically distinctive. However, the distinction between
      passerines and other birds remains a significant correlate of avian BMR, even
      after six ecological factors are included, with other birds having BMRs that
      averaged 74% of the passerine mean. This combination of factors accounts for
      97.7% of the variation in avian BMR. Yet, migratory species that belong to
      Anseriformes, Charadriiformes, Pelecaniformes, and Procellariiformes and breed in
      temperate or polar environments have mass-independent basal rates equal to those
      found in passerines. In contrast, penguins belong to an order of polar, aquatic
      birds that have basal rates lower than passerines because their flightless
      condition depresses basal rate. Passerines dominate temperate, terrestrial
      environments and the four orders of aquatic birds dominate temperate and polar
      aquatic environments because their high BMRs facilitate reproduction and
      migration. The low BMRs of tropical passerines may reflect a sedentary lifestyle
      as much as a life in a tropical climate. Birds have BMRs that are 30-40% greater
      than mammals because of the commitment of birds to an expensive and expansive
      form of flight.

PMID- 18805500
TI  - Bothrops jararaca fibrinogen and its resistance to hydrolysis evoked by snake
      venoms.
AB  - Fibrinogen is an essential protein involved in several steps of hemostasis, being
      associated with the final steps of the blood coagulation mechanism. Herein, we
      describe the purification and characterization of a reptile fibrinogen, obtained
      from Bothrops jararaca plasma. Native B. jararaca fibrinogen showed a molecular
      mass of 372 kDa, and the reduced and alkylated fibrinogen molecule showed three
      chains of 71, 60 and 55 kDa, which are similar to the molecular masses of human
      and bovine Aalpha, Bbeta and gamma fibrinogen chains. Remarkably, B. jararaca
      fibrinogen was clotted by bovine thrombin, but B. jararaca, Crotalus durissus
      terrificus and Lachesis muta rhombeata venoms could not induce its clotting or
      hydrolysis. Thus, despite the similarities between B. jararaca and mammalian
      fibrinogens, the former shows distinctive features, which protect B. jararaca
      snakes from accidental envenomation.

PMID- 18805501
TI  - Production of phenylpropanoid amides in recombinant Escherichia coli.
AB  - Plant-specific phenylpropanoid amides were produced in a recombinant Escherichia
      coli that expressed 4-coumarate:coenzyme A ligase from Arabidopsis and serotonin
      N-hydroxycinnamoyltransferase from pepper plants. Upon exogenous treatment with
      several precursors, high concentrations of the following phenylpropanoid amides
      were produced abundantly in the culture medium in a few hours: 4
      coumaroylserotonin (215 mg/l), 4-coumaroyloctopamine (208 mg/l), and 4
      coumaroyltyramine (187 mg/l).

PMID- 18805502
TI  - Dual mechanism of deltaEF1 expression regulated by bone morphogenetic protein-6
      in breast cancer.
AB  - The metastatic nature of breast cancer has been well recognized, yet the
      mechanisms through which breast cancer cells acquire their invasive properties
      have not been clearly elucidated. Our previous study indicates that BMP-6
      restores E-cadherin-mediated EMT through repressing deltaEF1 in breast cancer.
      However, the mechanism by which BMP-6 regulates deltaEF1 expression remains
      unclear. In this study, we confirmed the significant role of BMP-6 in inhibiting
      MDA-MB-231 migration through decreasing deltaEF1 expression which subsequently
      relieves deltaEF1-mediated invasion. The inhibitory effect of BMP-6 through
      deltaEF1 regulation was supported by an inverse correlation of BMP-6/miR-192 and
      deltaEF1 expressions observed in both MDA-MB-231 and MCF-7 cells and clinical
      tumor specimens. Moreover, BMP-6 treatment or miR-192 transfection decreased the
      reporter activity of the deltaEF1 3'-UTR-luc, validating that deltaEF1 is a
      target of miR-192. Meanwhile, we also found that BMP-6 acted as a potent
      transcriptional repressor of the human deltaEF1 promoter. Mutation of the AP-1
      binding site on this promoter abolished BMP-6-induced transrepression of
      deltaEF1. Depletion of BMP-6 expression by RNAi resulted in a significant
      increase in the promoter activity of deltaEF1. Our study has provided novel
      findings of a dual mechanism for BMP-6-regulated deltaEF1 expression in breast
      cancer cells, involving cross-talks between AP-1-mediated transcriptional
      repression and miRs-mediated translational inhibition.

PMID- 18805503
TI  - Marking time: the dynamic role of chromatin and covalent modification in
      transcription.
AB  - The expression of genes subject to strict regulation can be a highly dynamic,
      cyclical process that sequentially achieves and then limits transcription.
      Kinetic investigations of the estrogen responsive pS2 (TFF1) promoter, to
      determine the occupancy of factors or the occurrence of covalent marks on
      chromatin, have provided the most comprehensive picture of the complexity of
      transcriptional cycling to date. Cycles are initiated by the assembly of
      intermediate transcription factors that in turn provoke conscription of the basal
      transcription machinery. These events then achieve activation of the polymerase
      II complex, which is subsequently followed by limitation of productivity through
      the action of repressive complexes. This latter phase resets the target promoter,
      through acting on chromatin structure, such that a subsequent cycle can be
      initiated. In consequence, transcription is dependent upon cis-acting elements
      (DNA and nucleosomes) that either interact with or are modified by trans-acting
      factors. Induced local structural changes to chromatin encompassing regulatory
      elements of gene promoters include alteration of the positional phasing of
      nucleosomes, substitution by variant histones, post-translational modification of
      nucleosomes, changes in the methylation of CpG dinucleotides and breaks in the
      sugar-phosphate backbone of DNA. A primary function of covalent modification of
      chromatin may be to drive a sequential progression of reversible interactions
      that achieve and regulate gene expression.

PMID- 18805504
TI  - Dynamin-related protein 1 mediates high glucose induced pancreatic beta cell
      apoptosis.
AB  - The pancreatic beta cell dysfunction is critical cycle in the pathogenesis of
      diabetes. Hyperglycemia is one of factors that induce pancreatic beta cell
      dysfunction, but the underlying mechanisms have not been well elucidated. In this
      study, we reported that a mitochondrial fission modulator, Dynamin-related
      protein 1 (Drp-1), plays an important role in high glucose induced beta cell
      apoptosis. Drp-1 expressed in islet beta cells was increased drastically under
      hyperglycemia conditions. Induction of Drp-1 expression significantly promoted
      high glucose induced apoptosis in Drp-1WT (Drp-1 wild type) inducible beta cell
      line, but not in Drp-1K38A (a dominant negative mutant of Drp1) inducible beta
      cell line. We further demonstrated that mitochondrial fission, cytochrome C
      release, mitochondrial membrane potential decreased, caspase-3 activation and
      generation of reactive oxygen species were enhanced by induction of Drp-1WT, but
      prevented by Drp-1K38A in pancreatic beta cells under high glucose condition.
      These results indicated that Drp-1 mediates high glucose induced pancreatic beta
      cell apoptosis.

PMID- 18805505
TI  - Engineered selenium-containing glutaredoxin displays strong glutathione
      peroxidase activity rivaling natural enzyme.
AB  - Insertion of selenocysteine (Sec) into protein scaffolds provides an opportunity
      for designing enzymes with improved and unusual catalytic properties. The use of
      a common thioredoxin fold with a high affinity for glutathione in glutaredoxin
      (Grx) and glutathione peroxidase (GPx) suggests a possibility of engineering Grx
      into GPx and vice versa. Here, we engineered a Grx domain of mouse
      thioredoxin/glutathione reductase (TGR) into a selenium-containing enzyme by
      substituting the active site cysteine (Cys) with selenocysteine (Sec) in a Cys
      auxotrophic system. The resulting selenoenzyme displayed an unusually high GPx
      catalytic activity rivaling that of several native GPxs. The engineered seleno
      Grx was characterized by mass spectrometry and kinetic analyses. It showed a
      typical ping-pong kinetic mechanism, and its catalytic properties were similar to
      those of naturally occurring GPxs. For example, its second rate constant
      (k(cat)/K(mH2O2)) was as high as 1.55x10(7) M(-1) min(-1). It appears that
      glutathione-dependent Grx, GPx and glutathione transferase (GST) evolved from a
      common thioredoxin-like ancestor to accommodate related glutathione-dependent
      functions and can be interconverted by targeted Sec insertion.

PMID- 18805506
TI  - Detection of micronucleated cells and gene expression changes in glandular
      stomach of mice treated with stomach-targeted carcinogens.
AB  - To assess the genotoxicity of chemicals on the stomach, we developed in vivo
      assays that can detect micronucleus induction and gene expression changes in
      epithelial cells of the glandular stomach in mice. Male BALB/c mice were orally
      given a single dose (100 mg/kg) of N-nitroso-N-methylurea (MNU) or N-methyl-N'
      nitro-N-nitrosoguanidine (MNNG) as stomach-targeted carcinogens. The glandular
      stomach was excised at 4h, 3 and 4 days after administration, and a single cell
      suspension of epithelial cells was prepared from the everted glandular stomach by
      EDTA treatment. For determination of micronucleus induction, gastric epithelial
      cells on days 3 and 4 after administration were fixed with 10% neutral-buffered
      formalin, stained with a combination of AO-DAPI, and analyzed under fluorescence
      microscopy. We also examined the induction of micronuclei in peripheral blood of
      these mice on days 2 and 3 after administration. Moreover, total RNA was
      extracted from gastric epithelial cells at 4h after administration, and p21 and
      plk2 expression was analyzed using a quantitative RT-PCR technique. 1) A
      significant increase of micronucleated cells was observed in the glandular
      stomach in mice treated with N-nitroso-N-methylurea (MNU) or N-methyl-N'-nitro-N
      nitrosoguanidine (MNNG) compared to mice treated with vehicle. 2) In peripheral
      blood, induction of micronuclei was observed in mice treated with MNU but not
      with MNNG. 3) p21 and plk2, which related to cell cycle arrest, were up-regulated
      in the glandular stomach in mice treated with MNU or MNNG compared to mice
      treated with vehicle. The present study showed that these assays using glandular
      stomach may help to evaluate the genotoxicity of chemicals after oral
      administration.

PMID- 18805507
TI  - Vasoprotective endothelial effects of a standardized grape product in humans.
AB  - The pathogenesis of coronary lesion development is a multi-factorial process
      involving a number of different cell types and covariates, and injury and
      dysfunction of the vascular endothelium is an important marker and likely
      participant in the initiation and/or progression of most forms of heart disease.
      In addition to chronic dysfunction of endothelial responses in patients with
      established heart disease, there is evidence that 'acute insults' can cause
      measurable dysfunction in vascular response in humans (drug toxicities, hypoxia,
      high fat meal). Such repeated acute insults may contribute to disease risk in
      otherwise healthy individuals or promote disease progression in established
      patients. Consumption of grape products, especially wine, has been linked to
      lower cardiovascular risk but the vascular endothelial effects of grape products
      in healthy normal subjects, in the absence of ethanol, have not been evaluated.
      We therefore tested the hypotheses that 1) a standardized product derived from
      fresh grapes (GP, acute and chronic consumption) improves endothelial performance
      in healthy normal young subjects, and 2) that concomitant grape consumption
      affects the 'acute endothelial insult' caused by a single standardized high fat
      meal (HF). Acute consumption of GP equivalent to 1.25 cups of fresh grapes caused
      significant improvement in brachial artery flow mediated dilation (FMD) within 3
      h of consumption, when compared to control consumption of sugar solution
      (p<0.05). No acute changes in heart rate, hemodynamics, or lipid profiles were
      observed. When this 'dose' was then consumed twice daily for 3 weeks FMD was
      further improved and total antioxidant capacity in plasma was slightly increased
      (p<0.05), with no change in heart rate, hemodynamics, or lipid profiles. A single
      HF meal (900 cal, 49 g total fat) caused a 50% reduction in FMD response when
      consumed alone, and this effect coincided with increased blood triglyceride
      levels within 3 h post-consumption. In contrast the concomitant consumption of GP
      with the HF meal completely prevented this HF-induced vascular endothelial
      dysfunction (p<0.05), but had no effect on rising triglycerides. These data
      demonstrate that a modest intake of fresh grapes can have acute favorable effects
      on vascular endothelial function in normal healthy subjects, that chronic intake
      can further improve performance and concomitant intake can blunt the 'acute
      insult' to endothelium caused by a typical western HF meal. This effect is likely
      to be related to antioxidant effects at the endothelium, rather than changes in
      blood lipids. These data support epidemiological data of the health benefits of
      grapes, and demonstrate that 'favorable' food consumption can apparently reduce
      some toxicities induced by 'unfavorable' food consumption.

PMID- 18805508
TI  - Activation of muscarinic receptors by a hydroalcoholic extract of Dicksonia
      sellowiana Presl. HooK (Dicksoniaceae) induces vascular relaxation and
      hypotension in rats.
AB  - Dicksonia sellowiana (Presl.) Hook is a native plant from the Central and South
      Americas that contain high levels of polyphenols, antioxidant compounds involved
      in protection against inflammation, cancer and cardiovascular risk. A
      phytomedicinal preparation obtained from aerial parts of D. sellowiana is
      currently under clinical evaluation in Brazil against asthma, and has been
      associated with several other beneficial effects. This study demonstrates that a
      hydroalcoholic extract obtained from D. sellowiana leaves (HEDS) fully relax, in
      a concentration-dependent manner, rat aortic rings precontracted with
      phenylephrine. Moreover, administration of HEDS (10, 20 and 40 mg/kg, i.v.) in
      anaesthetized rats resulted in a strong but reversible hypotension. Aortic
      relaxation induced by HEDS was abolished by endothelium removal, by incubation of
      the nitric oxide synthase inhibitor L-NAME, or the soluble guanylate cyclase
      inhibitor ODQ. In addition, this effect was partially inhibited by indomethacin
      (a cyclooxygenase inhibitor) and KT 5730 (a PKA inhibitor). The potassium
      channels blockade by either tetraethylammonium or charybdotoxin also resulted in
      a potent inhibition of HEDS-induced aortic relaxation, whereas apamine only
      slightly reduced it. In addition HEDS-induced relaxation was unchanged by 4
      amynopiridine and glibenclamide. The selective muscarinic receptor antagonist
      atropine counteracted both aortic relaxation and blood pressure reduction
      generated by HEDS. Experiments using HPLC revealed the presence of high amounts
      of phenolic compounds in this extract. Taken together, our results reveal that
      the D. sellowiana possess substances with both in vivo and in vitro activities
      and that the vascular effect of HEDS involves activation of muscarinic receptors,
      stimulation of the nitric oxide pathway and opening of calcium-activated
      potassium channels.

PMID- 18805509
TI  - A randomized trial to determine the impact on compliance of a psychophysical
      peripheral cue based on the Elaboration Likelihood Model.
AB  - OBJECTIVE: Non-compliance in clinical studies is a significant issue, but causes
      remain unclear. Utilizing the Elaboration Likelihood Model of persuasion, this
      study assessed the psychophysical peripheral cue 'Interactive Voice Response
      System (IVRS) call frequency' on compliance. METHODS: 71 participants were
      randomized to once daily (OD), twice daily (BID) or three times daily (TID) call
      schedules over two weeks. Participants completed 30-item cognitive function tests
      at each call. Compliance was defined as proportion of expected calls within a
      narrow window (+/- 30 min around scheduled time), and within a relaxed window (
      30 min to +4 h). Data were analyzed by ANOVA and pairwise comparisons adjusted by
      the Bonferroni correction. RESULTS: There was a relationship between call
      frequency and compliance. Bonferroni adjusted pairwise comparisons showed
      significantly higher compliance (p=0.03) for the BID (51.0%) than TID (30.3%) for
      the narrow window; for the extended window, compliance was higher (p=0.04) with
      OD (59.5%), than TID (38.4%). CONCLUSION: The IVRS psychophysical peripheral cue
      call frequency supported the ELM as a route to persuasion. The results also
      support OD strategy for optimal compliance. Models suggest specific indicators to
      enhance compliance with medication dosing and electronic patient diaries to
      improve health outcomes and data integrity respectively.

PMID- 18805510
TI  - Modifications of a large HIV prevention clinical trial to fit changing realities:
      a case study of the Breastfeeding, Antiretroviral, and Nutrition (BAN) protocol
      in Lilongwe, Malawi.
AB  - In order to evaluate strategies to reduce HIV transmission through breast milk
      and optimize both maternal and infant health among HIV-infected women and their
      infants, we designed and implemented a large, randomized clinical trial in
      Lilongwe, Malawi. The development of protocols for large, randomized clinical
      trials is a complicated and lengthy process often requiring alterations to the
      original research design. Many factors lead to delays and changes, including
      study site-specific priorities, new scientific information becoming available,
      the involvement of national and international human subject committees and
      monitoring boards, and alterations in medical practice and guidance at local,
      national, and international levels. When planning and implementing a clinical
      study in a resource-limited setting, additional factors must be taken into
      account, including local customs and program needs, language and socio-cultural
      barriers, high background rates of malnutrition and endemic diseases, extreme
      poverty, lack of personnel, and limited infrastructure. Investigators must be
      prepared to modify the protocol as necessary in order to ensure participant
      safety and successful implementation of study procedures. This paper describes
      the process of designing, implementing, and subsequently modifying the
      Breastfeeding, Antiretrovirals, and Nutrition, (BAN) Study, a large, on-going,
      randomized breastfeeding intervention trial of HIV-infected women and their
      infants conducted at a single-site in Lilongwe, Malawi. We highlight some of the
      successes, challenges, and lessons learned at different stages during the conduct
      of the trial.

PMID- 18805511
TI  - Effects of a selection of histone deacetylase inhibitors on mast cell activation
      and airway and colonic smooth muscle contraction.
AB  - Studies of histone deacetylase (HDAC) inhibitors, novel anticancer drugs, in
      models of autoimmune diseases, asthma, and inflammatory bowel disease suggest
      that HDAC inhibitors may also have useful anti-inflammatory effects. Accordingly,
      in vitro studies relevant to asthma and inflammatory bowel disease were conducted
      using a selection of HDAC inhibitors: suberoylanilide hydroxamic acid (SAHA,
      Vorinostat), and a related branched hydroxamic acid, diamide (1), MGCD0103 and
      two short chain fatty acid derivatives: sodium butyrate (of use in inflammatory
      bowel disease) and sodium valproate. The ability of those HDAC inhibitors to
      modulate antigen- or agonist-induced contraction of isolated guinea pig tracheal
      rings and colon, agonist-induced contraction of rat colon, and histamine release
      from rat peritoneal mast cells was examined. Pre-incubation (up to 6 h) with 10
      40 microM of SAHA, diamide (1), or MGCD0103 caused significant inhibition of the
      antigen-induced contraction of sensitised guinea pig tracheal rings as well as
      inhibition of the contraction induced by histamine, 5-hydroxytryptamine and
      carbachol (G-protein coupled receptor agonists), while sodium butyrate (1 mM) and
      sodium valproate (100 microM) were weak inhibitors. Contraction of tracheal rings
      by sodium fluoride (NaF, a non-selective G-protein activator), KCl and a peroxyl
      radical generator was blocked by MGCD0103. Additionally, MGCD0103 significantly
      inhibited antigen-induced histamine release from IgE antibody-sensitised rat
      peritoneal mast cells, and NaF-induced histamine release, as well as inhibiting
      NaF-induced colon contraction. Those various effects appear to involve modulation
      of cell signaling, probably involving G-protein coupled pathways, and further
      support the development of HDAC inhibitors as anti-inflammatory agents.

PMID- 18805513
TI  - The structure of horseradish peroxidase C characterized as a molten globule state
      after Ca(2+) depletion.
AB  - The structure and activity of native horseradish peroxidase C (HRP) is stabilized
      by two bound Ca(2+) ions. Earlier studies suggested a critical role of one of the
      bound Ca(2+) ions but with conflicting conclusions concerning their respective
      importance. In this work we compare the native and totally Ca(2+)-depleted forms
      of the enzyme using pH-, pressure-, viscosity- and temperature-dependent UV
      absorption, CD, H/D exchange-FTIR spectroscopy and by binding the substrate
      benzohydroxamic acid (BHA). We report that Ca(2+)-depletion does not change the
      alpha helical content of the protein, but strongly modifies the tertiary
      structure and dynamics to yield a homogeneously loosened molten globule-like
      structure. We relate observed tertiary changes in the heme pocket to changes in
      the dipole orientation and coordination of a distal water molecule. Deprotonation
      of distal His42, linked to Asp43, itself coordinated to the distal Ca(2+),
      perturbs a H-bonding network connecting this Ca(2+) to the heme crevice that
      involves the distal water. The measured effects of Ca(2)(+) depletion can be
      interpreted as supporting a structural role for the distal Ca(2+) and for its
      enhanced significance in finetuning the protein structure to optimize enzyme
      activity.

PMID- 18805512
TI  - WRN protects against topo I but not topo II inhibitors by preventing DNA break
      formation.
AB  - The Werner syndrome helicase/3'-exonuclease (WRN) is a major component of the DNA
      repair and replication machinery. To analyze whether WRN is involved in the
      repair of topoisomerase-induced DNA damage we utilized U2-OS cells, in which WRN
      is stably down-regulated (wrn-kd), and the corresponding wild-type cells (wrn
      wt). We show that cells not expressing WRN are hypersensitive to the toxic effect
      of the topoisomerase I inhibitor topotecan, but not to the topoisomerase II
      inhibitor etoposide. This was shown by mass survival assays, colony formation and
      induction of apoptosis. Upon topotecan treatment WRN deficient cells showed
      enhanced DNA replication inhibition and S-phase arrest, whereas after treatment
      with etoposide they showed the same cell cycle response as the wild-type. A
      considerable difference between WRN and wild-type cells was observed for DNA
      single- and double-strand break formation in response to topotecan. Topotecan
      induced DNA single-strand breaks 6h after treatment. In both wrn-wt and wrn-kd
      cells these breaks were repaired at similar kinetics. However, in wrn-kd but not
      wrn-wt cells they were converted into DNA double-strand breaks (DSBs) at high
      frequency, as shown by neutral comet assay and phosphorylation of H2AX. Our data
      provide evidence that WRN is involved in the repair of topoisomerase I, but not
      topoisomerase II-induced DNA damage, most likely via preventing the conversion of
      DNA single-strand breaks into DSBs during the resolution of stalled replication
      forks at topo I-DNA complexes. We suggest that the WRN status of tumor cells
      impacts anticancer therapy with topoisomerase I, but not topoisomerase II
      inhibitors.

PMID- 18805514
TI  - Recurrence of preeclampsia: effects of paternity, birth interval, and choice of
      methodology.

PMID- 18805515
TI  - How to avoid unnecessary laparotomies in iatrogenic bile duct injuries?

PMID- 18805516
TI  - Unrecognized risk factors in acute appendicitis.

PMID- 18805517
TI  - The RIFLE classification for acute kidney injury definition.

PMID- 18805518
TI  - Orofacial dysfunction in Duchenne muscular dystrophy.
AB  - Duchenne muscular dystrophy (DMD) affects orofacial function. Our aim was to
      evaluate certain characteristics of orofacial function in DMD and relate possible
      deteriorations to the age of the patients and to the diminished internal
      structure quality of the masseter muscle. Bite force and finger force were
      measured in 16 DMD patients (6-20 years old) and 16 age matched controls. The
      thickness and internal structure quality of the masseter muscle were evaluated
      ultrasonographically. We found reduced mouth opening but no signs of masticatory
      muscle tenderness. Bite force values were lower for DMD patients. Masseter
      thickness showed no significant differences between the two groups, but poorer
      internal muscle structure quality characterised the elder, non-walking DMD
      patients explaining their low bite force values. In conclusion, the masseter
      muscle follows the general progress of the disease. Orofacial function in DMD
      patients is becoming ever more important as their life expectancy increases.

PMID- 18805519
TI  - Synthesis and biological activity of novel thiazolidin-4-ones with a carbohydrate
      moiety.
AB  - Some novel 2-aryl-3-[5-deoxy-1,2-O-isopropylidene-alpha-D-xylofuranose-5-C-yl]
      thiazolidin-4-ones were synthesized by the three-component condensation of an
      amino sugar 1, an aromatic aldehyde 2, and mercaptoacetic acid 3 in the presence
      of DCC and DMAP at room temperature. Two diastereoisomers 4 and 5 were afforded
      as the main products in totally isolated yields of 25.4-70%. The reaction was
      carried out with almost no observed stereoselectivity except in the case of 2c,
      which showed a moderate stereoselectivity. The structures of the new compounds
      were determined by NMR spectroscopy and mass spectrometry (MS), and the
      configuration of the newly generated chiral carbon (C-2) in the thiazolidin-4-one
      ring was tentatively assigned based on the X-ray crystallographic structure of 5d
      and the comparison of their corresponding NMR signals. The antitumor (human
      cervical cancer cells) activity and the inhibition against the glycosidases
      (alpha-glucosidase, beta-glucosidase, alpha-amylase) have been evaluated for the
      new compounds, some of which exhibited antitumor activity.

PMID- 18805520
TI  - Introducing N-glycans into natural products through a chemoenzymatic approach.
AB  - The present study describes an efficient chemoenzymatic method for introducing a
      core N-glycan of glycoprotein origin into various lipophilic natural products. It
      was found that the endo-beta-N-acetylglucosaminidase from Arthrobactor
      protophormiae (Endo-A) had broad substrate specificity and can accommodate a wide
      range of glucose (Glc)- or N-acetylglucosamine (GlcNAc)-containing natural
      products as acceptors for transglycosylation, when an N-glycan oxazoline was used
      as a donor substrate. Using lithocholic acid as a model compound, we have shown
      that introduction of an N-glycan could be achieved by a two-step approach:
      chemical glycosylation to introduce a monosaccharide (Glc or GlcNAc) as a handle,
      and then Endo-A catalyzed transglycosylation to accomplish the site-specific N
      glycan attachment. For those natural products that already carry terminal Glc or
      GlcNAc residues, direct enzymatic transglycosylation using sugar oxazoline as the
      donor substrate was achievable to introduce an N-glycan. It was also demonstrated
      that simultaneous double glycosylation could be fulfilled when the natural
      product contains two Glc residues. This chemoenzymatic method is concise, site
      specific, and highly convergent. Because N-glycans of glycoprotein origin can
      serve as ligands for diverse lectins and cell-surface receptors, introduction of
      a defined N-glycan into biologically significant natural products may bestow
      novel properties onto these natural products for drug discovery and development.

PMID- 18805521
TI  - A basidiomycetous yeast, Pseudozyma crassa, produces novel diastereomers of
      conventional mannosylerythritol lipids as glycolipid biosurfactants.
AB  - Mannosylerythritol lipids (MELs) are glycolipid biosurfactants produced by the
      yeast strains of the genus Pseudozyma. These compounds show not only excellent
      surface-active properties, but also versatile biochemical actions. During a
      survey of new MEL producers, we found that a basidiomycetous yeast, Pseudozyma
      crassa, extracellularly produces three glycolipids. When glucose and oleic acid
      were used as the carbon source, the total amount of glycolipids reached
      approximately 4.6g/L in the culture medium. The structures of these glycolipids
      were similar to those of well-known MEL-A, -B, and -C, respectively. Very
      interestingly, in all the present glycolipids, the configuration of the
      erythritol moiety was entirely opposite to that of conventional MELs. The present
      glycolipids were identified to have the carbohydrate structure of 4-O-beta-D
      mannopyranosyl-(2R,3S)-erythritol, stereochemically different from 4-O-beta-D
      mannopyranosyl-(2S,3R)-erythritol of conventional MELs. Furthermore, these new
      glycolipids possessed both short-chain acids (C(2) or C(4)) and long-chain acids
      (C(14), C(16), or C(18)) on the mannose moiety. The major component of the
      present glycolipids clearly showed different interfacial and biological
      properties, compared to conventional MELs comprising two medium-chain acids on
      the mannose moiety. Accordingly, the novel MEL diastereomers produced by P.
      crassa should provide us with different glycolipid functions, and facilitate a
      broad range of applications of MELs.

PMID- 18805522
TI  - The link between speech perception and production is phonological and abstract:
      evidence from the shadowing task.
AB  - This study reports a shadowing experiment, in which one has to repeat a speech
      stimulus as fast as possible. We tested claims about a direct link between
      perception and production based on speech gestures, and obtained two types of
      counterevidence. First, shadowing is not slowed down by a gestural mismatch
      between stimulus and response. Second, phonetic detail is more likely to be
      imitated in a shadowing task if it is phonologically relevant. This is consistent
      with the idea that speech perception and speech production are only loosely
      coupled, on an abstract phonological level.

PMID- 18805523
TI  - Bilateral uterine artery ligation via minilaparotomy for heavy menstrual
      bleeding.
AB  - OBJECTIVE: To assess the safety and short-term efficacy of bilateral uterine
      artery ligation (UAL) via minilaparotomy for the management of heavy menstrual
      bleeding (HMB). METHODS: A prospective study of 30 women with HMB who underwent
      UAL. The primary outcome was cumulative treatment failure 12 months after the
      procedure. Treatment failure was defined as the need for hysterectomy during the
      follow-up period. RESULTS: At 12 months, 6 women had undergone hysterectomy for
      bleeding, for a cumulative failure rate of 20% (95% CI, 9%-38%). The number of
      bleeding days was significantly reduced by 11.9+/-1.5 days (P<0.001) and
      hemoglobin level significantly increased by 1.3+/-0.15 g/dL (P<0.001). Of the 30
      women, 24 (80%) were satisfied with the results. No major complications were
      reported during the procedure or median follow-up period of 13.2 months.
      CONCLUSION: Bilateral UAL is a safe and effective minimally invasive procedure
      that can provide an alternative treatment for HMB.

PMID- 18805524
TI  - Isosorbide mononitrate versus alendronate for postmenopausal osteoporosis.
AB  - OBJECTIVE: To compare the effectiveness, safety, and affordability of isosorbide
      mononitrate with alendronate for postmenopausal osteoporosis. METHODS: A
      randomized controlled trial of 60 postmenopausal women with osteoporosis.
      Participants were randomly assigned to receive either 20 mg daily of isosorbide
      mononitrate or 70 mg weekly of alendronate for 12 months. Bone mineral density
      (BMD) was measured using dual X-ray absorptiometry (DXA) at baseline and after 12
      months. RESULTS: Both groups showed significant improvement in BMD. Isosorbide
      mononitrate yielded a comparable effect to alendronate for BMD and T-score at the
      end of the follow-up period. For BMD and T score the mean differences between the
      2 groups were -0.005 (95% CI, -0.02 to 0.03) and 0.31 (95% CI, -0.03 to 0.64),
      respectively. A 10.8% and 12.1% change in BMD after 12 months was seen for
      isosorbide mononitrate and alendronate, respectively. CONCLUSION: Isosorbide
      mononitrate is comparable to alendronate. Nitric oxide donors may be an effective
      and affordable therapy to improve bone mineral density.

PMID- 18805525
TI  - Safe motherhood and newborn health: FIGO projects and progress.

PMID- 18805526
TI  - Mechanical properties of physiological and pathological models of collagen
      peptides investigated via steered molecular dynamics simulations.
AB  - In this work we used molecular simulations to investigate the elastic properties
      of collagen single chain and triple helix with the aim of understanding its
      features starting from first principles. We analysed ideal collagen peptides,
      homotrimeric and heterotrimeric collagen type I and pathological models of
      collagen. Triple helices were found much more rigid than single chains, thus
      enlightening the important role of interchain stabilizing forces, like
      hydrophobic interaction and hydrogen bonds. We obtained Young's moduli close to
      4.5GPa for the ideal model of collagen and for the physiological heterotrimer,
      while the physiological homotrimer presented a Young's modulus of 2.51GPa, that
      can be related to a mild form of Osteogenesis Imperfecta in which only the
      homotrimeric form of collagen type I is produced. Otherwise, the pathological
      model (presenting a glycine to alanine substitution) showed an elastic modulus of
      4.32GPa, thus only slightly lower than the ideal model. This suggests that this
      mutation only slightly affects the mechanical properties of the collagen
      molecule, but possibly acts on an higher scale, such as the packing of collagen
      fibrils.

PMID- 18805527
TI  - Control of knee coronal plane moment via modulation of center of pressure: a
      prospective gait analysis study.
AB  - OBJECTIVES: Footwear-generated biomechanical manipulations (e.g., wedge insoles)
      have been shown to reduce the magnitude of adduction moment about the knee. The
      theory behind wedged insoles is that a more laterally shifted location of the
      center of pressure reduces the distance between the ground reaction force and the
      center of the knee joint, thereby reducing adduction moment during gait. However,
      the relationship between the center of pressure and the knee adduction moment has
      not been studied previously. The aim of this study was to examine the association
      between the location of the center of pressure and the relative magnitude of the
      knee adduction moment during gait in healthy men. METHODS: A novel foot-worn
      biomechanical device which allows controlled manipulation of the center of
      pressure location was utilized. Twelve healthy men underwent successive gait
      analysis testing in a controlled setting and with the device set to convey three
      different para-sagittal locations of the center of pressure: neutral, medial
      offset and lateral offset. RESULTS: The knee adduction moment during the stance
      phase significantly correlated with the shift of the center of pressure from the
      functional neutral sagittal axis in the coronal plane (i.e., from medial to
      lateral). The moment was reduced with the lateral sagittal axis configuration and
      augmented with the medial sagittal axis configuration. CONCLUSIONS: The study
      results confirm the hypothesis of a direct correlation between the coronal
      location of the center of pressure and the magnitude of the knee adduction
      moment.

PMID- 18805528
TI  - Noninvasive determination of spatial distribution and temporal gradient of wall
      shear stress at common carotid artery.
AB  - Wall shear stress (WSS) has been proved to play a critical role in formation and
      development of atherosclerotic plaques. Our objective was to quantify local WSS
      in vivo in normal subjects, and to analyze spatial distribution patterns and
      determine the temporal gradient of WSS. Seventy-eight CCAs of 42 healthy
      volunteers at common carotid arteries (CCAs) were studied. Cine phase-contrast MR
      sequence was used to acquire the flow velocity information. Three-dimensional
      paraboloid modeling was applied to fit the velocity profiles and WSS values were
      calculated. Mean WSS value for CCAs was 0.783+/-0.209, with the range of WSS
      value from -0.541 to 3.464 N/m(2). The 95% confidence interval for mean WSS value
      in CCA was (0.736-0.830) N/m(2). Different WSS spatial distribution patterns were
      classified into three types according to the location of low WSS values during a
      cardiac cycle. Mean value of maximum temporal gradient of WSS was 14.12+/-5.46,
      with the range from 5.87 to 33.23 N/m(2)s(-1). Skewed velocity profiles were
      displayed in most CCAs, indicating the flow patterns in CCA were more complicated
      than commonly assumed. Obvious inter-subject variation were found in magnitude,
      spatial distribution and the temporal gradient of WSS in CCAs, and the blood flow
      patterns as well.

PMID- 18805529
TI  - Biomechanical response of the human mandible to impacts of the chin.
AB  - The purpose of this study was to determine the force-time and force-displacement
      response of the human mandible under direct loading at the chin. Sub-fracture
      response of the mandible and temporomandibular joint (TMJ) were analyzed from 10
      cadavers that were impacted at the chin with a 2.8-kg mass at drop heights of
      300, 400 and 500 mm and a 5.2-kg mass at 500 mm. Motion of radio-opaque markers
      adhered to the surface of the bone was recorded at 1000 Hz by a bi-planar X-ray
      and converted to three-dimensional coordinates. Peak force ranged from 0.90 to
      4.54 kN causing chin displacement of 1.2-4.4 mm. A bi-linear response was
      observed with stiffness of 475.1+/-199.8 kN/m for chin displacement resulting
      from loading up to 0.6 kN and 2381.6+/-495.7 kN/m for loads from 0.6 to 3.25 kN.
      This defines the biomechanical response of the mandible for chin motion under
      impact loading. The response of different segments of the mandible and TMJ are
      also documented. Force-time and force-displacement response corridors for the
      mandible can be used for finite element model and/or the development and
      validation of a biomechanical surrogate.

PMID- 18805530
TI  - Effect of LIMK2 RNAi on reorganization of the actin cytoskeleton in osteoblasts
      induced by fluid shear stress.
AB  - The biomechanical characteristics of bone tissue and its cells under mechanical
      stress are significant for bone biomechanics research, but the mechanism of
      mechanotransduction is still unknown. It has been established that the actin
      cytoskeleton of osteoblasts plays an important role in this process. However, the
      structure of the actin cytoskeleton is reorganized when loaded with mechanical
      stress, which results in changes in cell stiffness. These phenomena suggest that
      an actin-cytoskeleton-induced feedback regulation mechanism may be involved in
      the mechanotransduction of osteoblasts, but this has not yet been proven. The aim
      of this study was to explore the role of LIMK2 in the reorganization of the actin
      cytoskeleton induced by fluid shear stress in osteoblasts by using RNA
      interference. Balb/c mouse primary osteoblasts were divided into four groups.
      Cells in Groups 1 and 3 were transfected with negative control RNA, while cells
      in Groups 2 and 4 were transfected with a specific siRNA designed to silence the
      LIMK2 gene. Twenty-four hours after transfection, cells in Groups 1 and 2 were
      loaded with fluid shear stress at 12 dyne/cm2 while cells in Groups 3 and 4 were
      not. Compared with Group 1, the mean fluorescence density of the actin
      cytoskeleton in the other three groups was 28.9%, 45.7%, and 33.0%, respectively.
      These results indicate that LIMK2 plays an important role in the reorganization
      of the actin cytoskeleton induced by fluid shear stress.

PMID- 18805532
TI  - Handling modular hip implants in model-based RSA: combined stem-head models.
AB  - Migration measurements of hip prostheses using marker-based Roentgen
      stereophotogrammetric analysis (RSA) require the attachment of markers to the
      prostheses. The model-based approach, which does not require these markers, is,
      however, less precise. One of the reasons may be the fact that the spherical head
      has not been modelled. Therefore, we added a 3D surface model of the spherical
      head and estimated the position and orientation of the combined stem-head model.
      The new method using a combined stem-head model was compared in a phantom study
      on five prostheses (of different types) and in a clinical study using double
      examinations of implanted hip prostheses, with two existing methods: a standard
      model-based approach and one using elementary geometrical shapes. The combined
      model showed the highest precision for the rotation about the longitudinal axis
      in the phantom experiments. With a standard deviation of 0.69 degrees it showed a
      significant improvement (p=0.02) over the model-based approach (0.96 degrees ) on
      the phantom data, but no improvement on the clinical data. Overall, the use of
      elementary geometrical shapes was worse with respect to the model-based approach,
      with a standard deviation of 1.02 degrees on the phantom data and 0.79 degrees on
      the clinical data. This decrease in precision was significant (p<0.01) on the
      clinical data. With relatively small differences in the other migration
      directions, these results demonstrate that the new method with a combined stem
      head model can be a useful alternative to the standard model-based approach.

PMID- 18805533
TI  - Evaluation of bone plate with low-stiffness material in terms of stress
      distribution.
AB  - The aim of this study is to evaluate a newly developed bone plate with low
      stiffness material in terms of stress distribution. In this numerical study, 3D
      finite element models of the bone plate with low-stiffness material and
      traditional bone plates made of stainless steel and Ti alloy have been developed
      by using the ANSYS software. Stress analyses have been carried out for all three
      models under the same loading and boundary conditions. Compressive stresses
      occurring in the intact portion of the bone (tibia) and at the fractured
      interface at different stages of bone healing have been investigated for all
      three types of bone-plate systems. The results obtained have been compared and
      presented in graphs. It has been seen that the bone plate with low-stiffness
      material offers less stress-shielding to the bone, providing a higher compressive
      stress at the fractured interface to induce accelerated healing in comparison
      with Ti alloy and stainless-steel bone plate. In addition, the effects of low
      stiffness materials with different Young's modulus on stress distribution at the
      fractured interface have been investigated in the newly developed bone-plate
      system. The results showed that when a certain value of Young's modulus of low
      stiffness material is exceeded, increase in stiffness of the bone plate does not
      occur to a large extent and stress distributions and micro-motions at the
      fractured interface do not change considerably.

PMID- 18805531
TI  - Stretch-activated force shedding, force recovery, and cytoskeletal remodeling in
      contractile fibroblasts.
AB  - The stress fiber network within contractile fibroblasts structurally reinforces
      and provides tension, or "tone", to tissues such as those found in healing
      wounds. Stress fibers have previously been observed to polymerize in response to
      mechanical forces. We observed that, when stretched sufficiently, contractile
      fibroblasts diminished the mechanical tractions they exert on their environment
      through depolymerization of actin filaments then restored tissue tension and
      rebuilt actin stress fibers through staged Ca(++)-dependent processes. These
      staged Ca(++)-modulated contractions consisted of a rapid phase that ended less
      than a minute after stretching, a plateau of inactivity, and a final gradual
      phase that required several minutes to complete. Active contractile forces during
      recovery scaled with the degree of rebuilding of the actin cytoskeleton. This
      complementary action demonstrates a programmed regulatory mechanism that protects
      cells from excessive stretch through choreographed active mechanical and
      biochemical healing responses.

PMID- 18805534
TI  - Assessment of in vivo and post-mortem mechanical behavior of brain tissue using
      magnetic resonance elastography.
AB  - The knowledge of in vivo brain tissue mechanical properties is essential in
      several biomedical engineering fields, such as injury biomechanics and
      neurosurgery simulation. Almost all existing available data have been obtained in
      vitro by invasive experimental protocols. However, the difference between in vivo
      and post-mortem mechanical properties remains poorly known, essentially due to
      the lack of a common method that could measure them both in vivo and ex vivo. In
      this study, we report the use of magnetic resonance elastography (MRE) for the
      non-invasive assessment of in vivo brain tissue viscoelastic properties and for
      the investigation of their evolution after the death. Experiments were performed
      on seven adult male rats. Shear storage and loss moduli were measured in vivo,
      just after death and at post-mortem time of approximately 24h. A significant
      increase in shear storage modulus G(') of approximately 100% was found to occur
      just after death (p=0.002), whereas no significant difference was found between
      in vivoG(') and G(') at 24h post-mortem time. No significant difference was found
      between shear loss modulus G('')in vivo and just after death, whereas a decrease
      of about 50% was found to occur after 24h (p=0.02). These results illustrate the
      ability of MRE to investigate some of the critical soft tissue biomechanics
      related issues, as it can be used as a non-invasive tool for measuring soft
      tissue viscoelastic properties.

PMID- 18805535
TI  - European Society of Biomechanics S.M. Perren Award 2008: using temporal trends of
      3D bone micro-architecture to predict bone quality.
AB  - In longitudinal studies, three-dimensional (3D) bone images are acquired at
      sequential time points essentially resulting in four-dimensional (4D) data for an
      individual. Based on the 4D data, we propose to calculate temporal trends and
      project these trends to estimate future bone architecture. Multiple consecutive
      deformation fields, calculated with Demons deformable image registration
      algorithm, were extrapolated on a voxel-by-voxel basis. Test data were from in
      vivo micro-computed tomography (microCT) scans of the proximal tibia of Wistar
      rats that were either ovariectomized (OVX; N=5) or sham operated (SHAM; N=6).
      Measurements performed at baseline, 4 and 8 weeks were the basis to predict the
      12 week data. Predicted and actual 12 week data were compared using qualitative
      (3D rendering) and quantitative (geometry, morphology and micro-finite element,
      microFE) methods. The results indicated a voxel-based linear extrapolation scheme
      yielded mean geometric errors that were smaller than the voxel size of 15 microm.
      Key morphological parameters that were estimated included bone volume ratio
      (BV/TV; mean error 0.4%, maximum error 9%), trabecular thickness (Tb.Th; -1.1%,
      11%), connectivity density (Conn.D; 9.0%, 18.5%) and the apparent Young's modulus
      (E(1); 6.0%, 32%). These data demonstrated a promising and novel approach for
      quantitatively capturing in vivo bone dynamics at the local trabecular level. The
      method does not require an a priori understanding of the diseases state, and can
      provide information about the trends of the bone remodeling process that may be
      used for better monitoring and treatment of diseases such as osteoporosis.

PMID- 18805536
TI  - Myofiber angle distributions in the ovine left ventricle do not conform to
      computationally optimized predictions.
AB  - Recent computational models of optimized left ventricular (LV) myofiber geometry
      that minimize the spatial variance in sarcomere length, stress, and ATP
      consumption have predicted that a midwall myofiber angle of 20 degrees and
      transmural myofiber angle gradient of 140 degrees from epicardium to endocardium
      is a functionally optimal LV myofiber geometry. In order to test the extent to
      which actual fiber angle distributions conform to this prediction, we measured
      local myofiber angles at an average of nine transmural depths in each of 32 sites
      (4 short-axis levels, 8 circumferentially distributed blocks in each level) in
      five normal ovine LVs. We found: (1) a mean midwall myofiber angle of -7 degrees
      (SD 9), but with spatial heterogeneity (averaging 0 degrees in the posterolateral
      and anterolateral wall near the papillary muscles, and -9 degrees in all other
      regions); and (2) an average transmural gradient of 93 degrees (SD 21), but with
      spatial heterogeneity (averaging a low of 51 degrees in the basal posterior
      sector and a high of 130 degrees in the mid-equatorial anterolateral sector). We
      conclude that midwall myofiber angles and transmural myofiber angle gradients in
      the ovine heart are regionally non-uniform and differ significantly from the
      predictions of present-day computationally optimized LV myofiber models. Myofiber
      geometry in the ovine heart may differ from other species, but model assumptions
      also underlie the discrepancy between experimental and computational results. To
      test the predictive capability of the current computational model would we
      propose using an ovine specific LV geometry and comparing the computed myofiber
      orientations to those we report herein.

PMID- 18805537
TI  - Different elution modes and field programming in gravitational field-flow
      fractionation. Effect of channel angle.
AB  - Gravitational field-flow fractionation (GrFFF) has been shown to be useful for
      separation and characterization of various types of micrometer-sized particles.
      It has been recognized however that GrFFF is less versatile than other members of
      FFF because the external field (Earth's gravity) in GrFFF is relatively weak and
      is not tunable (constant), which makes the force acting on the particles
      constant. A few approaches have been suggested to control the force acting on
      particles in GrFFF. They include (1) changing the angle between the Earth's
      gravitational field and the longitudinal axis of the channel, and (2) the use of
      carrier liquid having different densities. In the hyperlayer mode of GrFFF, the
      hydrodynamic lift force (HLF) also act on particles. The existence of HLF allows
      other means of changing the force acting on the particles in GrFFF. They include
      (1) the flow rate programming, or (2) the use of channels having non-constant
      cross-section. In this study, with polystyrene latex beads used as model
      particles, the channel angle was varied to study its effect on elution parameters
      (such as selectivity, band broadening and resolution) in the steric or in the
      hyperlayer mode of GrFFF. In addition, the effects of the channel thickness and
      the flow rate on the elution parameters were also investigated. It was found
      that, in the steric mode, the resolution decreases as the flow rate increases due
      to increased zone broadening despite of the increase in the selectivity. At a
      constant volumetric flow rate, both the zone broadening and the selectivity
      increase as the channel thickness increases, resulting in the net increase in the
      resolution. It was also found that the retention time decreases as the channel
      angle increases in both up- and down-flow positions. The zone broadening tends to
      increase almost linearly with the channel angle, while no particular trends were
      found in selectivity. As a result, the resolution decreases as the channel angle
      increases.

PMID- 18805538
TI  - Advances in stir bar sorptive extraction for the determination of acidic
      pharmaceuticals in environmental water matrices Comparison between polyurethane
      and polydimethylsiloxane polymeric phases.
AB  - Stir bar sorptive extraction with polyurethane (PU) and polydimethylsiloxane
      (PDMS) polymeric phases followed by high-performance liquid chromatography with
      diode array detection [SBSE(PU or PDMS)/HPLC-DAD] was studied for the
      determination of six acidic pharmaceuticals [o-acetylsalicylic acid (ACA),
      ibuprofen (IBU), diclofenac sodium (DIC), naproxen (NAP), mefenamic acid (MEF)
      and gemfibrozil (GEM)], selected as non-steroidal acidic anti-inflammatory drugs
      and lipid regulators model compounds in environmental water matrices. The main
      parameters affecting the efficiency of the proposed methodology are fully
      discussed. Assays performed on 25 mL of water samples spiked at the 10 microg L(
      1) level under optimized experimental conditions, yielded recoveries ranging from
      45.3+/-9.0% (ACA) to 90.6+/-7.2% (IBU) by SBSE(PU) and 9.8+/-1.6% (NAP) to 73.4+/
      5.0% (GEM) by SBSE(PDMS), where the former polymeric phase presented a better
      affinity to extract these target analytes from water matrices at the trace level.
      The methodology showed also excellent linear dynamic ranges for the six acidic
      pharmaceuticals studied, with correlation coefficients higher than 0.9976, limits
      of detection and quantification between 0.40-1.7 microg L(-1) and 1.5-5.8 microg
      L(-1), respectively, and suitable precision (RSD <15%). Moreover, the developed
      methodology was applied for the determination of these target analytes in several
      environmental matrices, including river, sea and wastewater samples, having
      achieved good performance and moderate matrix effects. In short, the PU foams
      demonstrated to be an excellent alternative for the enrichment of the more polar
      metabolites from water matrices by SBSE, overcoming the limitations of the
      conventional PDMS phase.

PMID- 18805539
TI  - Polymeric ionic liquids as selective coatings for the extraction of esters using
      solid-phase microextraction.
AB  - A new class of stationary phase coatings for solid-phase microextraction (SPME)
      based on polymeric ionic liquids (PILs) is presented. PIL-based SPME coatings
      exhibit exceptional film stability, high thermal stability, reproducible
      extraction efficiencies, and long lifetimes. A series of three homologous
      polymeric imidazolium-based ionic liquid coatings were synthesized by free
      radical reaction. The fiber coatings were used to extract esters and fatty acid
      methyl esters from aqueous solution followed by gas chromatographic separation
      and flame ionization detection. To examine the effect of the matrix on the
      coatings, extractions were carried out in a synthetic wine solution followed by
      recovery experiments in two real wine samples. When carrying out the extractions
      in aqueous solution, the detection limits for most analytes ranged from 2.5 to
      50microgL(-1) whereas lower detection limits were obtained for larger fatty acid
      methyl esters. Recovery experiments carried out in red and white wines ranged
      from 70.2% to 115.1% using the PIL fibers compared to 61.9% to 102.9% using a
      commercial polydimethylsiloxane fiber of similar film thickness. The structural
      tuning capability of these new coating materials makes them widely amendable to
      performing task-specific microextractions.

PMID- 18805540
TI  - Analysis of quaternary ammonium and phosphonium ionic liquids by reversed-phase
      high-performance liquid chromatography with charged aerosol detection and unified
      calibration.
AB  - Several hydrophobic ionic liquids (ILs) based on long-chain aliphatic ammonium-
      and phosphonium cations and selected aromatic anions were analyzed by reversed
      phase high-performance liquid chromatography (RP-HPLC) employing trifluoroacetic
      acid as ion-pairing additive to the acetonitrile-containing mobile phase and
      adopting a step-gradient elution mode. The coupling of charged aerosol detection
      (CAD) for the non-chromophoric aliphatic cations with diode array detection (DAD)
      for the aromatic anions allowed their simultaneous analysis in a set of new ILs
      derived from either tricaprylmethylammonium chloride (Aliquat 336) and
      trihexyltetradecylphosphonium chloride as precursors. Aliquat 336 is a mix of
      ammonium cations with distinct aliphatic chain lengths. In the course of the
      studies it turned out that CAD generates an identical detection response for all
      the distinct aliphatic cations. Due to lack of single component standards of the
      individual Aliquat 336 cation species, a unified calibration function was
      established for the quantitative analysis of the quaternary ammonium cations of
      the ILs. The developed method was validated according to ICH guidelines, which
      confirmed the validity of the unified calibration. The application of the method
      revealed molar ratios of cation to anion close to 1 indicating a quantitative
      exchange of the chloride ions of the precursors by the various aromatic anions in
      the course of the synthesis of new ILs. Anomalies of CAD observed for the
      detection of some aromatic anions (thiosalicylate and benzoate) are discussed.

PMID- 18805541
TI  - Considerations for environmental fate and ecotoxicity testing to support
      environmental risk assessments for engineered nanoparticles.
AB  - There is an increasing concern over the safety of engineered nanoparticles (ENPs)
      to humans and the environment and it is likely that the environmental risks of
      these particles will have to be tested under regulatory schemes such as REACH.
      Due to their unique properties and the fact that their detection and
      characterisation in complex matrices is challenging, existing analytical methods
      and test approaches for assessing environmental risk may not be appropriate for
      ENPs. In this article we discuss the challenges associated with the testing of
      ENPs to generate data on persistence, mobility, bioavailability and ecotoxicity
      in the environment. It is essential that careful consideration is given to the
      selection of the test material, the test system (including test vessels and study
      media) and the test exposure conditions. During a study it is critical that not
      only the concentration of the ENP is determined but also its characteristics
      (e.g. size, shape, degree of aggregation and dissolution). A range of analytical
      techniques is available including microscopy-based approaches (e.g transmission
      and scanning electron microscopy), dynamic light scattering, and size separation
      approaches (e.g. field flow fractionation and hydrodynamic chromatography)
      coupled to detection methods such as inductively coupled plasma MS. All of these
      have their disadvantages: some are unable to distinguish between ENPs and natural
      interferences; some techniques require sample preparation approaches that can
      introduce artefacts; and others are complex and time-consuming. A combination of
      techniques is therefore needed. Our knowledge in this area is still limited, and
      co-ordinated research is required to gain a better understanding of the factors
      and processes affecting ENP fate and effects in the environment as well as to
      develop more usable, robust and sensitive methods for characterisation and
      detection of ENPs in environmental systems.

PMID- 18805542
TI  - One-step synthesis of organic-inorganic hybrid asymmetric dimer particles via
      miniemulsion polymerization and functionalization with silver.
AB  - Organic-inorganic polystyrene (PSt)-silica (SiO2) hybrid asymmetric particles
      were prepared in one step by a miniemulsion polymerization technique. The organic
      and inorganic reagents were confined in miniemulsion microreactor droplets. After
      the formation of PSt and SiO2, internal phase separation inside the droplets was
      accelerated owing to the hydrophobicity of PSt and the hydrophilicity of SiO2.
      Therefore, PSt-SiO2 hybrid asymmetric particles could be synthesized in one step.
      Between each pair of asymmetric particles, silane couplers act as bridges
      connecting the PSt and SiO2 particles. The size of PSt particles in these
      asymmetric particles was easily tuned either by changing the weight ratio of
      St/TEOS or by varying the sonication power during the miniemulsion preparation.
      After functionalization of the as-prepared asymmetric dimers by surface
      decoration with Ag particles, enhanced surface-enhanced Raman scattering (SERS)
      properties were observed due to electromagnetic enhancement of the added Ag
      colloids.

PMID- 18805543
TI  - Proximal placement of limb electrodes: a potential solution for acquiring
      standard electrocardiogram waveforms from monitoring electrode positions.
AB  - There is currently a challenge to produce an electrocardiogram (ECG) recording of
      waveforms that are "standard" and also achieve the "noise immunity" required for
      continuous monitoring. The potential solutions that have been considered are to
      label each torso-recorded ECG as "nonstandard, torso-recorded," designate torso
      placement as "standard," or to reconstruct the "equivalent distally recorded
      ECG." The purpose of the present study was to validate an alternative "Lund
      system" of proximal limb electrode sites as a clinically feasible solution to
      this challenge. Data were collected from 75 patients referred for exercise
      testing at the Lund University Hospital. The Lund system produced Q wave
      dimensions and frontal plane QRS axis measurements that were in much better
      agreement with the standard ECG than those variables recorded with the Mason
      Likar torso limb electrode method. Indeed, the Lund system replicated distal
      waveforms at a clinically acceptable level. Studies of larger patient cohorts
      including patients with various cardiac pathologies and studies of the noise
      immunity attained should be performed, and the acceptability by health care
      professionals should be determined.

PMID- 18805544
TI  - The development of idiom comprehension: an investigation of semantic and
      contextual processing skills.
AB  - Two experiments compared 7- and 8-year-olds' and 9- and 10-year-olds' ability to
      use semantic analysis and inference from context to understand idioms. We used a
      multiple-choice task and manipulated whether the idioms were transparent or
      opaque, familiar or novel, and presented with or without a supportive story
      context. Performance was compared with that of adults (Experiment 1) and 11- and
      12-year-olds (Experiment 2). The results broadly support Cacciari and Levorato's
      global elaboration model of figurative competence with a notable exception: Even
      the youngest children were able to use semantic analysis to derive the meanings
      of transparent idioms as well as being sensitive to meaning in context. The
      findings show that young children process language at both the small-grain phrase
      level and the discourse level to establish figurative meaning, and they
      demonstrate that the language processing skills that aid idiom comprehension, as
      well as idiom knowledge itself, are still not fully developed in 11- and 12-year
      olds.

PMID- 18805545
TI  - Vascular flow of the gastric fundus after arterial devascularization: an
      experimental study.
AB  - BACKGROUND: The main complication of transhiatal subtotal esophagectomy with
      esophagogastric reconstruction is anastomotic leak, which is responsible for a
      large number of postoperative deaths. It is believed that this complication is
      due to gastric fundus ischemia caused by the sectioning of the short gastric,
      left gastric, and left gastro-omental arteries. The literature, however, presents
      controversies. An experimental study was performed with the aim of evaluating the
      vascularization of the gastric fundus following sectioning of these arteries.
      MATERIALS AND METHODS: Forty mongrel dogs were distributed into 2 groups: a
      control group consisting of 15 dogs subjected to surgical simulation and an
      experimental group consisting of 25 dogs that underwent sectioning of these
      arteries. Fluorescein testing, gastric mummification, and morphometric image
      analysis were performed on both groups. RESULTS: In comparison with the control
      group, fluorescein testing on the experimental group demonstrated time-delayed
      fluorescence in the gastric fundus and partial coloring, (P < 0.001). Image
      analysis on the mummified gastric samples demonstrated significant reduction in
      blood vessels in the gastric fundus of the experimental group (P < 0.001).
      CONCLUSIONS: We conclude that sectioning of the short gastric, left gastric, and
      left gastro-omental arteries causes reduction in blood circulation and in the
      quantity of blood vessels on the anterior side of the gastric fundus of dogs.

PMID- 18805546
TI  - Plaunotol and geranylgeraniol induce caspase-mediated apoptosis in colon cancer.
AB  - BACKGROUND: Plaunotol, a kind of isoprenoid extracted from a Thai medical plant,
      plau-noi, is structurally similar to geranylgeraniol (GGOH), another isoprenoid
      reported to exert strong anticancer effects. Recently, we have reported on its
      inhibitory effects on tumor angiogenesis and direct effects on gastric cancer
      cells. Here, we aimed to test whether plaunotol could have some therapeutic
      effect on colon cancer. MATERIALS AND METHODS: Human colon cancer cell line DLD1
      was used. Tumor cells were cultured in the presence of plaunotol or GGOH, and
      their proliferation was measured by MTS assay. Apoptosis was evaluated by Annexin
      V and propidium iodide double-staining or terminal-deoxynucleotidyl assay. The
      activation of caspase-3, -8, and -9 was analyzed by flow cytometry and Western
      blot analysis for PRRP cleavage. RESULTS: Plaunotol and GGOH strongly inhibited
      the proliferative activity of DLD1, dependent on induction of apoptosis. The
      induction of apoptosis by either plaunotol or GGOH was dependent on the
      activation of both caspase-8 and caspase-9 pathways. CONCLUSIONS: Plaunotol would
      be a potential anticancer agent against colon cancer, and since it is already
      available in Japan and Thailand for clinical use as an anti-ulcer/antigastritis
      agent, clinical trials will be designed to confirm the present findings.

PMID- 18805547
TI  - Sutureless pancreatojejunal anastomosis using an absorbable sealant: evaluation
      in a pig model.
AB  - BACKGROUND: Leakage from pancreatojejunal anastomosis continues to be a major
      source of morbidity in pancreatic surgery. In the present study, we test the
      hypothesis that a safe, sutureless pancreatojejunal anastomosis can be
      constructed using a synthetic surgical sealant. MATERIALS AND METHODS: Ten pigs
      weighing 20 to 25 kg underwent distal pancreatectomy and anastomosis of the
      pancreatic remnant with a jejunal limb with the use of an absorbable surgical
      sealant. Integrity of the anastomosis was checked on the 10th postoperative d by
      means of an autopsy study and histological examination. RESULTS: One animal died
      on the 3rd postoperative d of peritonitis. The remaining 9 animals had an
      uneventful postoperative course. Gross and microscopic pathological examination
      revealed intact pancreatojejunal anastomosis in all surviving animals.
      CONCLUSIONS: Following distal pancreatectomy in pigs, pancreatojejunal
      anastomoses with the use of sealant are technically feasible. During a 10-d
      observation period, the sealant appeared to prevent anastomotic dehiscence and
      allow normal anastomotic healing.

PMID- 18805548
TI  - Quality of life is not quality of clerkship.

PMID- 18805549
TI  - Inducible nitric oxide synthase expression in the intestinal muscularis mediates
      severe smooth muscle dysfunction during acute rejection in allogenic rodent small
      bowel transplantation.
AB  - BACKGROUND: Acute rejection in small bowel transplantation is associated with
      dysmotility. Therefore, host and organ not only face the threat of destructive
      immunological processes but also the risk of bacterial translocation,
      endotoxemia, and systemic inflammatory response syndrome. We hypothesized that
      dysmotility during acute rejection is based on an alloreactive leukocyte
      infiltrate and coexpression of the kinetically active mediator inducible nitric
      oxide synthase (iNOS) in the muscularis propria. MATERIALS AND METHODS: Allogenic
      and isogenic rat small bowel transplantation (SBTx; Brown Norway [BN] to Lewis
      and BN to BN) was performed without immunosuppression. Animals were sacrificed 4
      and 7 d after SBTx. Leukocyte infiltration and iNOS protein was investigated by
      immunohistochemistry and immunohistology. Real-time reverse transcription polymer
      chain reaction was used to detect iNOS expression. Griess reaction was used to
      evaluate NO production. Spontaneous, bethanechol-stimulated, and L-N(6)-(1
      iminoethyl)-L-Lysin-blocked jejunal circular muscle contractions were measured in
      a standard organ bath in vitro. RESULTS: On d 7 after SBTx, allogenic
      transplanted animals showed significant infiltration with ED-1- and ED-2-positive
      monocytes and macrophages within the muscularis parallel to the manifestation of
      acute rejection. Additionally, immunohistochemistry localized iNOS protein in
      leukocytes within the muscularis. Reverse transcription polymer chain reaction
      showed a significant increase in iNOS mRNA expression (460-fold) in allogenic
      transplanted muscularis compared to isogenic transplanted muscularis (2.5-fold).
      Compared to controls, allogenic grafts showed a 73% decrease in smooth muscle
      contractility, while isogenic grafts showed only an 8% decrease of contractility
      on d 7. L-N(6)-(1-iminoethyl)-L-Lysin application in vitro significantly improved
      muscle contractility and decreased NO production. CONCLUSION: The data show that
      inflammation associated iNOS expression in the intestinal graft muscularis is
      involved in motoric graft dysfunction during acute rejection.

PMID- 18805550
TI  - Bioimpedance analysis: a guide to simple design and implementation.
AB  - BACKGROUND: Bioimpedance analysis has found utility in many fields of medical
      research, yet instrumentation can be expensive and/or complicated to build.
      Advancements in electronic component design and equipment allow for simple
      bioimpedance analysis using equipment now commonly found in an engineering lab,
      combined with a few components exclusive to impedance analysis. MATERIALS AND
      METHODS: A modified Howland bridge circuit was designed on a small circuit board
      with connections for power and bioimpedance probes. A programmable function
      generator and an oscilloscope were connected to a laptop computer and were tasked
      to drive and receive data from the circuit. The software then parsed the received
      data and inserted it into a spreadsheet for subsequent data analysis. The circuit
      was validated by testing its current output over a range of frequencies and
      comparing measured values of impedance across a test circuit to expected values.
      RESULTS: The system was validated over frequencies between 1 and 100 kHz. Maximum
      fluctuation in current was on the order of micro-Amperes. Similarly, the measured
      value of impedance in a test circuit followed the pattern of actual impedance
      over the range of frequencies measured. CONCLUSIONS: Contemporary generation
      electronic measurement equipment provides adequate levels of connectivity and
      programmability to rapidly measure and record data for bioimpedance research.
      These components allow for the rapid development of a simple but accurate
      bioimpedance measurement system that can be assembled by individuals with limited
      knowledge of electronics or programming.

PMID- 18805551
TI  - Topical mitogen-activated protein kinases inhibition reduces intimal hyperplasia
      in arterialized vein grafts.
AB  - OBJECTIVE: Vein graft arterialization results in activation of the mitogen
      activated protein kinases (MAPKs) extracellular signal-regulated kinases-1 and -2
      (ERK1/2), which have been implicated in cell proliferation, migration, and
      apoptosis. The goal of our study was to characterize the effect of MAPK
      inhibition on intimal hyperplasia (IH) in arterialized vein grafts in
      hypercholesterolemic rabbits. METHODS: Reversed bilateral jugular vein to common
      carotid artery interposition grafts were constructed in 16 New Zealand White
      rabbits. The veins were incubated for 30 min prior to grafting with either the
      synthetic ERK1/2 activation inhibitor UO126 or the control vehicle. Vein graft
      and control jugular vein were harvested 3 h, 1 d, and 28 d after arterialization
      for histological and biochemical analyses. RESULTS: Treatment with UO126 was
      associated with 31% reduction in mean intimal area (1.68 +/- 0.78 mm(2)versus
      2.44 +/- 1.65 mm(2); mean +/- SD; P = 0.036) relative to controls. The intima-to
      media ratio of UO126-treated vein grafts decreased by 29% (0.53 +/- 0.04 versus
      0.74 +/- 0.06; mean +/- SD; P < 0.01) compared to controls, vehicle-treated vein
      grafts. There was also significant increase in apoptosis in UO126-treated vein
      graft medial cell layer at 1 d. CONCLUSION: Topical administration of UO126
      before vein grafting significantly decreases IH in arterialized vein grafts in
      hypercholesterolemic rabbits. These results may have significant implications for
      the development of strategies aimed at blocking or reducing IH in bypass grafts.
      Therefore, further evaluation of this simple strategy to improve vein graft
      patency following coronary artery or peripheral vascular bypass surgery is
      warranted.

PMID- 18805552
TI  - Use of scene vital signs improves TRISS predicted survival in intubated trauma
      patients.
AB  - INTRODUCTION: The Trauma Related Injury Severity Score (TRISS) has been
      previously validated to predict outcomes in nonintubated, nonparalyzed trauma
      patients. The purpose of this study was to assess the impact of scene vital signs
      on predicting survival in intubated trauma patients. METHODS: Our Trauma Registry
      of the American College of Surgeons was reviewed for all trauma patients admitted
      between 10/01/04 and 09/30/06, arriving by aeromedical transport. TRISS was
      evaluated for each patient based on their (1) scene vital signs and (2) arrival
      vital signs. Additionally, the "TRISS-like" score was calculated for each
      patient. Expected mortality for each score was measured against observed
      mortality. RESULTS: Four thousand four hundred ninety-nine Trauma Registry of the
      American College of Surgeons patients were admitted during the study period; 695
      (15%) were transported by air; 163 patients (23%) arrived intubated; 480 arrived
      nonintubated. Observed survival in the intubated group was 76%. Observed survival
      in the nonintubated group was 100%. TRISS using scene vital signs more closely
      predicted mortality among intubated patients than the other scoring systems (69%
      versus 39% using TRISS-arrival versus 80% using TRISS-like). Scene vital signs
      with TRISS also resulted in fewer "unexpected" outcomes (survivors and deaths).
      CONCLUSIONS: Traditionally, patients arriving at trauma centers intubated are
      either excluded from the trauma registry or have their physiological score
      "modified" to account for pharmacologically altered respiratory rate and Glasgow
      Coma Scale. In intubated patients, TRISS using scene vital signs more reliably
      predicts survival and does so with far fewer "unexpected" outcomes than with
      other available scoring systems.

PMID- 18805553
TI  - Autoimmune-mediated oxidative stress and endothelial dysfunction: implications of
      accelerated vascular injury in type I diabetes.
AB  - The pathogenesis of cardiovascular disease in the setting of type 1 diabetes is
      not well-defined. The hypothesis that hyperglycemia is largely responsible for
      vascular endothelial dysfunction, and ultimately atherosclerosis, continues to
      evolve. However, despite tight glucose control, a subset of patients still
      develop clinically significant occlusive disease. While the specific mechanisms
      of persistent vascular injury are not clear, an increasing body of evidence
      suggests a dysregulated autoimmune response may contribute to the development of
      vascular injury. That is, the same inflammatory response that is responsible for
      pancreatic beta-cell destruction may facilitate chronic vascular endothelial
      injury prior to the onset of hyperglycemia. Herein, we discuss (1) the clinical
      experience with tight glycemic control and the risk of cardiovascular disease in
      patients with type 1 diabetes; (2) the cellular mechanisms involved in vascular
      endothelial injury; and (3) the long-term clinical implications of autoimmune
      mediated vascular disease and current treatment strategies.

PMID- 18805554
TI  - Mechanism of injury predicts patient mortality and impairment after blunt trauma.
AB  - BACKGROUND: Different mechanisms of injury (MOI), such as motor vehicle crashes,
      falls, or pedestrians struck by motor vehicle impart varying degrees of force and
      energy transfer that may impact outcomes. This study analyzed the independent
      relationship between MOI and mortality and functional outcomes following blunt
      trauma among adults. MATERIALS AND METHODS: Retrospective review of blunt trauma
      patients 15 y and older in the National Trauma Data Bank from 2001 to 2005.
      Primary outcome measures were mortality and presence of functional deficit in
      speech, walking, or feeding at discharge. MOI categories, identified by ICD-9 E
      codes, were motor vehicle crash, pedestrian struck by motor vehicle, motorcycle
      crash, falls at same level and from any height, and bicycle crash. A multiple
      regression analysis was performed adjusting for patient demographics and injury
      severity variables with motor vehicle crash as the reference mechanism group.
      RESULTS: Over the period studied, 515,464 patients met inclusion criteria. Mean
      Injury Severity Score (16.9), mortality rate (11%), and extremity injury (20%)
      were highest among pedestrians struck by motor vehicle, and head injury (16%)
      highest for motorcyclists. Overall, 52% had impaired ambulation, 16% impaired
      feeding, and 10% impaired speech. Adjusted odds of death, impaired walking, and
      impaired speaking were highest for pedestrians struck by motor vehicle, and
      impaired feeding highest for motorcyclists. CONCLUSION: After adjusting for
      confounders, MOI was found to independently predict mortality and functional
      impairment at hospital discharge. Current injury assessment models could be
      greatly enhanced by including MOI, and we propose routine adjustment for injury
      mechanism in trauma outcomes research.

PMID- 18805555
TI  - Are neonatal stem cells as effective as adult stem cells in providing ischemic
      protection?
AB  - BACKGROUND: Bone marrow stem cells (BMSCs) may be a novel treatment modality for
      organ ischemia, possibly through beneficial paracrine mechanisms. However, stem
      cells from older hosts exhibit decreased function during stress. We therefore
      hypothesized that (1) BMSCs derived from neonatal hosts would provide protection
      to ischemic myocardium, and (2) neonatal stem cells would enhance postischemic
      myocardial recovery above that seen with adult stem cell therapy. MATERIALS AND
      METHODS: Female adult Sprague Dawley rat hearts were subjected to an
      ischemia/reperfusion protocol via Langendorff isolated heart preparation (15 min
      equilibration, 25 min ischemia, and 60 min reperfusion). BMSCs were harvested
      from adult and neonatal mice and cultured through several passages under normal
      conditions (37 degrees C, 5% CO(2)/air). Immediately prior to ischemia, 1 million
      adult or neonatal BMSCs were infused into the coronary circulation. Cardiac
      functional parameters were continuously recorded. RESULTS: Pretreatment with
      adult BMSCs significantly increased postischemic myocardial recovery as noted by
      improved left ventricular developed pressure, end diastolic pressure,
      contractility, and rate of relaxation. Neonatal stem cells, however, did not
      cause any noticeable improvement in myocardial functional parameters following
      ischemia. CONCLUSION: Neonatal and adult BMSCs are distinctly different in the
      degree of beneficial tissue protection that they can provide. The data herein
      suggests that a critical age exists as to when stem cells become fully activated
      to provide their beneficial protective properties. Defining the genes that
      initiate these protective properties may allow for genetic amplification of
      beneficial signals, and the generation of "super stem cells" that provide maximum
      protection to ischemic tissues.

PMID- 18805556
TI  - Aquaporin-4 antibody positive longitudinally extensive transverse myelitis
      following varicella zoster infection.
AB  - Longitudinally extensive transverse myelitis (LETM) is a condition shown to
      confer high risk of conversion into neuromyelitis optica (NMO). Increasing
      evidence from immunological and histopathological studies suggests that LETM is
      an autoimmune disorder caused by pathogenic antibodies to aquaporin-4 (AQP4-Ab),
      the most abundant water channel in the CNS, at least in a subset of patients.
      However, cases of infectious or parainfectious NMO/LETM (mostly associated with
      herpes zoster) have been repeatedly reported in the previous literature, raising
      the question of aetiological diversity in NMO/LETM. Here we present a case of
      acute LETM in a 63-year-old patient occurring two weeks after reactivation of
      varicella zoster virus (VZV). Serological testing revealed antibodies to AQP4.
      Plasma exchange was paralleled by disappearance of AQP4-Ab and sustained clinical
      improvement. Our observations provide further evidence for a pathogenic role of
      AQP4-Ab in LETM and suggest that AQP4-Ab associated auto-immunity should be
      considered also in apparently infectious/parainfectious settings.

PMID- 18805557
TI  - Genetic polymorphism of Angiotensin-Converting Enzyme is not associated with the
      development of Parkinson's disease and of L-dopa-induced adverse effects.
AB  - Sporadic Parkinson's disease (PD) is a frequent neurodegenerative movement
      disorder. Both environmental and genetic factors have been studied in the
      etiology of PD. Among genetic factors, increasing evidences suggest that
      deletion/insertion (D/I) gene polymorphism of the angiotensin I-converting enzyme
      (ACE) may be involved in the pathogenesis of PD and in the occurrence of the
      adverse effects of chronic L-dopa therapy. We investigated this hypothesis by
      evaluating the frequency of the ACE gene D/I polymorphism in 120 Italian PD
      patients and 132 controls. Out of the 120 PD patients, 91 were under chronic L
      dopa treatment. Our results revealed no difference in ACE I/D genotype
      (chi(2)=0.79, p=0.66) and allele (chi(2)=0.34, p=0.56) frequencies between PD and
      controls. We also failed to observe any significant association with the
      occurrence of L-dopa-induced adverse effects in long-term treated PD patients,
      thereby excluding the presence of an association between ACE I/D genotypes and
      the genetic susceptibility to PD and the development of adverse effect of chronic
      L-dopa therapy.

PMID- 18805558
TI  - Comparison of the role of two Spartina species in terms of phytostabilization and
      bioaccumulation of metals in the estuarine sediment.
AB  - In the joint estuary of the Odiel and Tinto rivers (SW Spain), the invasive
      Spartina densiflora Brongn. and the native Spartina maritima (Curtis) Fernald are
      growing over sediments with extreme concentrations of heavy metals. The contents
      of As, Cu, Fe, Mn, Pb and Zn were determined in sediments, rhizosediments and
      different tissues of both species, from Odiel and Tinto marshes. S. densiflora
      showed a higher capability to retain metals around their roots and to control the
      uptake or transport of metals, mediated by a higher formation of plaques of Fe/Mn
      (hydro) oxides on the roots. At the Tinto marsh, there were no differences
      between the metal concentrations of the sediment and those of the rhizosediment,
      a fact that could be explained by the extremely high concentrations of metals
      which can pass over a threshold value, altering the properties of root cells and
      preventing roots from acting as a 'barrier' to the uptake or transport of metals.

PMID- 18805559
TI  - Effect of age and gender in the pharmacokinetics of albendazole and albendazole
      sulphoxide enantiomers in goats.
AB  - The kinetics of albendazole metabolites and albendazole sulphoxide enantiomers
      were studied in 2- and 14-month-old female and male goats, after a single oral
      dose administration (10mg/kg) of an albendazole formulation. Blood samples from
      the jugular vein were collected at 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 20, 24, 30,
      36, 42, 48 and 54h post-treatment and analyzed using a high performance liquid
      chromatography method. In all groups the area under the plasma concentration-time
      curve (AUC) and peak concentration (C(max)) values of (+)-ABZSO were
      significantly higher than those of (-)-ABZSO. The AUC and C(max) values obtained
      for (+)-ABZSO and (-)-ABZSO in adult animals were higher compared to the results
      in young animals, showing significant differences except for (+)-ABZSO in female
      animals. In young animals, independently of gender, the C(max) appeared earlier
      compared to adult animals. The mean residence time (MRT) values were shorter in
      young animals compared to adult animals for all compounds analyzed. No sex
      related differences were found for any of the parameters calculated except for
      the (+)-ABZSO from adult animals.

PMID- 18805560
TI  - [Thymolipoma revelated by myasthenia].
AB  - Thymolipomas are rare, often asymptomatic benign tumors; their revelation by
      myasthenia is exceptional. A 49-year-old patient with a one-year history of
      fluctuant muscular fatigability developed ptosis. Electromyography revealed a
      myasthenic neuromuscular block. The CT scan disclosed a thymic mass especially
      important on the left side. Thoracotomy under left mammary was performed for
      thymectomy. Pathology examination of the surgical specimen provided the diagnosis
      of benign thymolipoma. At 37 months follow-up, the myasthenia has remained
      unchanged.

PMID- 18805561
TI  - Identification of functionally important amino acid residues in the mitochondria
      targeting sequence of hepatitis B virus X protein.
AB  - Chronic hepatitis B virus (HBV) infection has been strongly associated with
      hepatocellular carcinoma (HCC) and the X protein (HBx) is thought to mediate the
      cellular changes associated with carcinogenesis. Recently, isolation of the
      hepatitis B virus integrants from HCC tissue by others have established the fact
      that the X gene is often truncated at its C-terminus. Expression of the GFP
      fusion proteins of HBx and its truncation mutants with a GFP tag in human liver
      cell-lines in this study revealed that the C-terminus of HBx is indispensable for
      its specific localization in the mitochondria. A crucial region of seven amino
      acids at the C-terminus has been mapped out in which the cysteine residue at
      position 115 serves as the most important residue for the subcellular
      localization. When cysteine 115 of HBx is mutated to alanine the mitochondria
      targeting property of HBx is abrogated.

PMID- 18805563
TI  - Resuspension of contaminated field and formulated reference sediments Part I:
      Evaluation of metal release under controlled laboratory conditions.
AB  - In aquatic systems where metal contaminated sediments are present, the potential
      exists for metals to be released to the water column when sediment resuspension
      occurs. The release and partitioning behavior of sediment-bound heavy metals is
      not well understood during resuspension events. In this study, the release of Cd,
      Cu, Hg, Ni, Pb and Zn from sediments during resuspension was evaluated using
      reference sediments with known physical and chemical properties. Sediment
      treatments with varying quantities of acid volatile sulfide (AVS), total organic
      carbon (TOC), and different grain size distributions were resuspended under
      controlled conditions to evaluate their respective effects on dissolved metal
      concentrations. AVS had the greatest effect on limiting release of dissolved
      metals, followed by grain size and TOC. Predictions of dissolved concentrations
      of Cd, Ni, Pb and Zn were developed based on the formulated sediment
      Sigma(metal)/AVS ratios with Sigma(metal) being the total sediment metal
      concentration. Predicted values were compared to measured dissolved metal
      concentrations in contaminated field sediments resuspended under identical
      operating conditions. Metal concentrations released from the field sediments were
      low overall, in most cases lower than predicted values, reflecting the importance
      of other binding phases. Overall, results indicate that for sulfidic sediments,
      low levels of the study metals are released to the dissolved phase during short
      term resuspension.

PMID- 18805562
TI  - Biological and genotypic properties of defective interfering particles of equine
      herpesvirus 1 that mediate persistent infection.
AB  - Infection with equine herpesvirus 1 (EHV-1) preparations enriched for defective
      interfering particles (DIP) leads to a state of persistent infection in which
      infected cells become lysis resistant and release both infectious (standard)
      virus and DIP. EHV-1 DIP are unique in that the recombination events that
      generate DIP genomes produce new open reading frames (ORFs; Hyb1.0 and Hyb2.0)
      consisting of 5' sequences of varying lengths of the early regulatory gene IR4
      fused to 3' sequences of varying lengths of the UL5 regulatory gene. Only two
      additional ORFs (UL3 and UL4) are conserved. Because persistently infected cells
      release a heterogeneous mixture of DIP, characterization of the elements
      responsible for this altered state of infection has proved difficult. Here we
      describe a method for studying persistent infection using recombinant DIP (rDIP).
      Infection with rDIP resulted in the production of recombinant DIP that replicated
      faithfully to, at least, five passages and mediated a rapid progression to
      persistent infection as measured by: 1) production of cells resistant to lysis by
      the standard virus; and 2) infected cells that released both standard virus and
      DIP. High concentrations of rDIP also resulted in interference with the standard
      virus replication, another hallmark of persistent infection. rDIP deleted of UL3,
      UL4, and either Hyb gene, the only functional genes conserved in the DIP genome,
      replicated but exhibited markedly reduced ability to interfere with standard
      virus replication. Restoring only the Hyb genes (either Hyb1.0 or Hyb2.0), the
      IR4 gene, or specific portions of the IR4 gene restored interference. These data
      suggest that residues 144 to 196 of the IR4 protein within the HYB proteins are
      important for DIP interference and that persistent infection results from
      recombination events that produce DIP genomes.

PMID- 18805564
TI  - Chloride leaching from air pollution control residues solidified using ground
      granulated blast furnace slag.
AB  - Ground granulated blast furnace slag (ggbs) has been used to solidify air
      pollution control (APC) residues obtained from a major UK energy-from-waste
      plant. Samples were prepared with ggbs additions between 10 and 50 wt% of total
      dry mass and water/solids ratios between 0.35 and 0.80. Consistence, setting
      time, compressive strength and leaching characteristics have been investigated.
      Results indicated that the highly alkaline nature of APC residues due to the
      presence of free lime can be used to activate ggbs hydration reactions.
      Increasing ggbs additions and reducing the water content resulted in increased
      compressive strengths, with 50 wt% ggbs samples having average 28 d strengths of
      20.6 MPa. Leaching tests indicate low physical encapsulation and minimal chemical
      fixation of chloride in ggbs solidified APC residues. The results suggest that
      more than 50 wt% ggbs additions would be required to treat APC residues to meet
      the current waste acceptance criteria limits for chloride.

PMID- 18805565
TI  - Is meltwater from Alpine glaciers a secondary DDT source for lakes?
AB  - A sharp increase in 2005 of pp'DDT and its metabolites was observed in mussels
      and fish from lakes Como and Iseo, the main glacier-fed southern Alpine lakes.
      DDTs in zebra mussels (Dreissena polymorpha) were more than 150 times higher than
      levels in 2003, and concentrations in pelagic fish (0.12 mgkg(-1) w.w.) exceeded
      the Italian safety threshold for human consumption (0.05 mgkg(-1) w.w.). The
      histological examination of the ovaries revealed many mussels with oocyte
      degeneration throughout the studied period. Prior to being banned in Italy in
      1978, DDT was used in large amounts for fruit-tree treatment from the 1950s to
      1970s in valleys just below the glaciers. Since glacier volume was increasing at
      that time and then continuously retreated, meltwater should be the main cause of
      the pollution peak recently observed in biota of downstream lakes. PCBs did not
      peak in biota tissues to a comparable extent probably because local sources were
      not as important as for DDTs.

PMID- 18805566
TI  - Contamination of River Kymijoki sediments with polychlorinated dibenzo-p-dioxins,
      dibenzofurans and mercury and their transport to the Gulf of Finland in the
      Baltic Sea.
AB  - Kymijoki, the fourth largest river in Finland, has been heavily polluted by pulp
      mill effluents as well as the chemical industry. Up to 24,000 ton of wood
      preservative, chlorophenol known as Ky-5, was manufactured in the upper reaches
      of the river, an unknown amount of which was discharged into the river between
      1940 and 1984. Polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs)
      occurred as impurities in the final Ky-5 product. The PCDD/F concentrations and
      burden in the river sediments were studied and the transport of PCDD/Fs from
      contaminated sites downstream and into the Gulf of Finland in the Baltic Sea was
      estimated. More than 190 sediment cores were sampled to estimate the volume of
      contaminated sediments and the total PCDD/F burden. The transport of PCDD/Fs was
      estimated using sediment traps placed at several sites. The survey revealed that
      sediments in the river were heavily polluted by PCDD/Fs, the main toxic congener
      being 1,2,3,4,6,7,8-heptachlorodibenzofuran, a major contaminant in the Ky-5
      product. The mean total concentration at the most polluted river site downstream
      from the main source was 42000 microg kg(-1) d.w. (106 microg I-TEQ kg(-1)). The
      elevated concentrations in the coastal region and the present estimated transport
      from the River Kymijoki confirm earlier assessments that the river is a major
      source of PCDD/F for the Gulf of Finland.

PMID- 18805567
TI  - Effects of long-term soil amendment with sewage sludges on soil humic acid
      thermal and molecular properties.
AB  - Sewage sludges are frequently used as soil amendments due to their high contents
      of organic matter and nutrients, particularly N and P. However, their effects
      upon the chemistry of soil humic acids, one of the main components of the soil
      organic matter, need to be more deeply studied in order to understand the
      relation between organic matter structure and beneficial soil properties. Two
      sewage sludges subjected to different types of pre-treatment (composted and
      thermally dried) with very different chemical compositions were applied for three
      consecutive years to an agricultural soil under long-term field study. Thermal
      analysis (TG-DTG-DTA) and solid-state (13)C NMR spectroscopy were used to compare
      molecular and structural properties of humic acids isolated from sewage sludges,
      and to determine changes in amended soils. Thermally dried sewage sludge humic
      acids showed an important presence of alkyl and O/N-alkyl compounds (70%) while
      composted sludge humic acids comprised 50% aromatic and carbonyl carbon. In spite
      of important differences in the initial chemical and thermal properties of the
      two types of sewage sludges, the chemical and thermal properties of the soil
      humic acids were quite similar to one another after 3 years of amendment. Long
      term application of both sewage sludges resulted in 80-90% enrichment in alkyl
      carbon and organic nitrogen contents of the soil humic acid fraction.

PMID- 18805568
TI  - Seasonal variation in drinking water concentrations of disinfection by-products
      in IZMIR and associated human health risks.
AB  - Seasonal variation in concentrations of two different disinfection by-product
      groups, trihalomethanes (THMs) and haloacetonitriles (HANs), was investigated in
      tap water samples collected from five sampling points (one groundwater and four
      surface water sources) in Izmir, Turkey. Estimates of previously published
      carcinogenic and non-carcinogenic risks through oral exposure to THMs were re
      evaluated using a probabilistic approach that took the seasonal concentration
      variation into account. Chloroform, bromoform, dibromochloromethane and
      dichloroacetonitrile were the most frequently detected compounds. Among these,
      chloroform was detected with the highest concentrations ranging from 0.03 to 98.4
      microg/L. In tap water, at the groundwater supplied sampling point, brominated
      species, bromoform and dibromoacetonitrile, were detected at the highest levels
      most probably due to bromide ion intrusion from seawater. The highest total THM
      and total HAN concentrations were detected in spring while the lowest in summer
      and fall. The annual average total THM concentration measured at one of the
      surface water supplied sampling points exceeded the USEPA's limit of 80 microg/L.
      While all non-carcinogenic risks due to exposure to THMs in Izmir drinking water
      were negligible, carcinogenic risk levels associated with bromodichloromethane
      and dibromochloromethane were higher than one in million.

PMID- 18805569
TI  - Assessment of mercury and methylmercury pollution with zebra mussel (Dreissena
      polymorpha) in the Ebro River (NE Spain) impacted by industrial hazardous dumps.
AB  - Large amounts of industrial waste containing high concentrations of mercury (up
      to 436 microg/g) are dumped in a reservoir adjacent to a chlor-alkali plant in
      Flix (Catalonia, Spain), on the lower Ebro River. In order to assess the spatial
      redistribution of mercury from the point source and its bioavailability to the
      aquatic food web, zebra mussels (Dreissena polymorpha) were collected at several
      sites. The highest total Hg (THg) and methylmercury (MeHg) concentrations ever
      reported for zebra mussels were found (THg: 0.02 to 0.81 microg/g ww; MeHg: 0.22
      to 0.60 microg/g ww). At the most polluted site, close to the waste dump, the
      mean values were 20 times greater than the local background level. Concentrations
      decreased with increasing mussel size at all sites. The MeHg/THg ratio was ca.
      60% (range: 50-80%). A comparison of similar size classes clearly indicated the
      hot spots of Hg bioavailability to the aquatic food web and downstream transport.

PMID- 18805570
TI  - Degradation and estrogenic activity removal of 17beta-estradiol and 17alpha
      ethinylestradiol by ozonation and O3/H2O2.
AB  - This work investigated the degradation of a natural (17beta-estradiol) and a
      synthetic (17alpha-ethinylestradiol) estrogens (pure or in the mixture) and the
      removal of estrogenic activity by the ozonation and O3/H2O2 process in three
      different pHs (3, 7 and 11). The effect of oxidation via OH radical was evaluated
      adding a radical scavenger (t-butanol) in the medium. Estrogenic activity was
      performed using the YES assay. 17beta-estradiol and 17alpha-ethinylestradiol
      presented similar estrogenic potential and the association of these estrogens
      resulted in an addictive effect for estrogenic activity. Ozonation and O3/H2O2
      processes were effective in removing the estrogens in aqueous solution. In the
      mixture at pH 11, removals were higher than 98% and 96% for 17beta-estradiol and
      17alpha-ethinylestradiol, respectively. In pH 3, 17beta-estradiol and 17alpha
      ethinylestradiol removals were 100% and 99.7%, respectively. When estrogens were
      treated separately, the removals in pH 11 were superior to 99.7 and 98.8%, while
      in pH 3 were 100% and 99.5% for 17beta-estradiol and 17alpha-ethinylestradiol,
      respectively. 17alpha-ethinylestradiol has been always removed at lower rates
      (pure or in the mixture) for all applied conditions. Estrogenic activity was
      completely removed in pH 3 for ozonation or O3/H2O2. The samples oxidized in pH
      11 presented higher estrogenic activity than those in pH 7. Estrogens removal was
      lower at pHs 7 and 11, when the scavenger was added to the media. The higher
      estrogen residual concentrations found in ozonation in presence of tert-butanol
      are contributing for higher estrogenic activity observed in pHs 7 and 11. By
      products with estrogenic activity were formed by oxidation via OH radical. Only a
      few compounds could be identified in pHs 7 and 11 and they have a phenolic ring,
      which, probably is contributing to the estrogenic activity observed.

PMID- 18805571
TI  - Short- and medium-term effects of fire and fire-fighting chemicals on soil
      micronutrient availability.
AB  - The impact of fire and three fire-fighting chemicals (FFC) on soil micronutrient
      availability was evaluated 1, 90 and 365 days after a prescribed fire. Five
      treatments were considered: unburnt soil (US) and burnt soil with 2 l m(-2) of
      water (BS) or water with foaming agent Auxquimica RFC-88 at 1% (BS+Fo), Firesorb
      at 1.5% (BS+Fi) and FR-Cross ammonium polyphosphate at 20% (BS+Ap). Pre-fire
      contents of available micronutrient were homogeneous among plots and high (Fe,
      Zn) or insufficient (Co, Cu, Mn) for plant nutrition. At t=1 day, Fe availability
      decreased greatly in burnt treatments, with significant differences in BS+Fi (
      50%) and BS+Ap (-75%), contrasting with Fe richness of the ammonium
      polyphosphate. The fire induced a significant increase (9-16x) of available Mn in
      burnt treatments that lasted for at least three months; the FFC effect on soil
      available Mn was imperceptible, despite the noticeable amounts of Mn they
      supplied (especially Firesorb and ammonium polyphosphate). In burnt soils, the
      Fe/Mn ratio also decreased strongly (92-99%) and significantly till t=90 days. A
      high increase was also found, at t=1 day, for the available Zn in all burnt
      treatments and, although the ammonium polyphosphate provided more Zn than the
      Firesorb, the increment was only significant in BS+Fi plots (+100%). Neither fire
      nor FFC effects on soil Cu availability were found. The slight increase of Co
      availability in BS, BS+Fo and BS+Ap at t=1 day was followed by a transient
      decrease in all burnt treatments at t=90 days. Except the Mn and the Fe/Mn ratio
      in BS+Ap, which remained significantly higher and lower, respectively, the
      indices of available micronutrients at t=365 days in all burnt soils were similar
      to the pre-fire levels.

PMID- 18805572
TI  - Distribution and neurotransmitter localization in the heart of the ray-finned
      fish, bichir (Polypterus bichir bichir Geoffroy St. Hilaire, 1802).
AB  - Anatomical and physiological studies of cardiovascular control are lacking in the
      ray-finned fish, the bichirs. The present immunohistochemical studies on the
      bichir (Polypterus bichir bichir) demonstrated the occurrence of intracardiac
      neurons and nerve fibers in the heart. Immunoreactivity to tyrosine hydroxylase
      (TH) and acetylcholinesterase (AchE) and various neuropeptides (substance P,
      galanin, vasoactive intestinal polypeptide (VIP) and pituitary adenylate cyclase
      activating peptide (PACAP)), including neuronal nitric oxide synthase (nNOS), was
      found in the nerve cell bodies lying close to the Sinus venosus and the sino
      atrial region. The main intracardiac localization of the nervous tissue is a
      network of nerve fibers, presumably corresponding to the postganglionic outflow
      giving rise to nerve terminals and the nerve cell bodies. In addition, the heart
      is innervated by extrinsic monoamine-containing nerve fibers supplying the Conus
      arteriosus and Sinus venosus, and substance P and galanin immunopositive fibers
      probably originating from cranial and spinal ganglia. The adrenergic innervation
      of the heart of the bichir is similar to that of the teleosts, but further
      studies are required on nervous control of the heart.

PMID- 18805573
TI  - Changing trends in presentation, diagnosis and management of renal
      angiomyolipoma: comparison of sporadic and tuberous sclerosis complex-associated
      forms.
AB  - OBJECTIVES: To evaluate the changing management of sporadic renal angiomyolipoma
      and renal angiomyolipoma associated with the tuberous sclerosis complex (TSC)
      during the past 16 years. METHODS: We retrospectively reviewed the charts of 60
      patients with angiomyolipoma seen at our institutions. RESULTS: The median age at
      presentation was 45 years (range 7-78). The presentation was pain in 30 patients
      and hematuria in 13; it was incidentally discovered in 17 patients. Of the 60
      patients, 43 were females. TSC was present in 14 patients. The median tumor size
      was 4 cm (range 0.3-40, mean 6.5 +/- 1.1). Of the 60 patients, 31 were followed
      up expectantly. Surgery or intervention was needed for 29 patients to control
      hemorrhage or relieve pain or because of the suspicion of malignancy. Of these 29
      patients, 12 underwent nephrectomy, 11 partial nephrectomy, and 6 embolization.
      The patients treated for hemorrhage had a median tumor diameter of 11 cm (range 2
      21). Patients were followed up for a mean of 39.3 +/- 5.4 months. The lesions
      grew an average of 4.7 +/- 3.4 cm for TSC tumors and 0.6 +/- 0.2 cm for sporadic
      angiomyolipoma tumors. None of the patients developed renal impairment. Patients
      with TSC presented at a younger age, had larger and bilateral lesions, and were
      more symptomatic during follow-up. In the past 6 years, a significant trend was
      seen toward finding tumors in asymptomatic patients and toward the use of
      conservative or interventional (embolization) treatment. CONCLUSIONS: Renal
      angiomyolipoma has a slow growth rate. The preservation of renal function was
      noted in all our patients. A recent shift was noted toward finding smaller tumors
      in asymptomatic patients and the use of conservative and interventional
      treatment.

PMID- 18805574
TI  - Robotic-assisted laparoscopic approach for posterior bladder neck dissection and
      placement of pediatric bladder neck sling: initial experience.
AB  - OBJECTIVES: Bladder neck sling cystourethropexy is a common procedure used to
      correct intrinsic sphincter deficiency in children with spinal dyspharism.
      Various modifications of the procedure have been made but all involve
      circumferential dissection of the bladder neck and proximal urethra. The
      posterior dissection can be challenging and can result in injury to the rectum,
      urethra, or vagina. The posterior approach to the bladder neck as reported by
      Lottmann and later by de Badiola addresses these potential complications. Using
      these principles of the posterior approach, we performed a robotic-assisted
      laparoscopic placement of an acellular human dermal allograft bladder neck sling
      in 2 patients. We present our initial experience regarding this surgical
      technique. METHODS: The diagnosis of intrinsic sphincter deficiency was
      established in 2 female patients, aged 9 and 10 years. Both patients had a
      neurogenic bladder secondary to spina bifida. Video urodynamics confirmed
      adequate bladder compliance and intrinsic sphincter deficiency. Robotic-assisted
      laparoscopic placement of a bladder neck sling was performed in both patients.
      RESULTS: Both procedures were completed intracorporeally. The mean blood loss was
      20 mL. The mean operative time was 189 minutes. No intraoperative or
      postoperative complications occurred. The mean hospital stay was 3 days (range 2
      4). The follow-up ranged from 13 to 22 months. Postoperative studies revealed
      continued low-pressure, compliant bladders and stable upper tracts. At last
      follow-up, the 2 patients were using catheterization without difficulty and were
      continent. CONCLUSIONS: The robotic-assisted laparoscopic approach to performing
      bladder neck dissection and placement of a bladder neck sling in children is
      technically feasible.

PMID- 18805575
TI  - Synchronous occult cancers of the endometrium and fallopian tube in an MSH2
      mutation carrier at time of prophylactic surgery.
AB  - BACKGROUND: Women with Lynch syndrome have a 40 to 60% lifetime risk of
      endometrial cancer and a 10 to 12% lifetime risk of ovarian cancer and may
      consider prophylactic gynecological surgery as an option for risk reduction.
      CASE: We report a case of synchronous primary cancers of the endometrium and
      fallopian tube diagnosed at time of prophylactic surgery in an MSH2 mutation
      carrier. CONCLUSION: Risk-reducing gynecological surgery in Lynch syndrome must
      include complete removal of the fallopian tubes in addition to the ovaries and
      endometrium, followed by careful pathological review. Prospective studies are
      needed to clarify the incidence of occult primary carcinoma of the fallopian tube
      among female MMR mutation carriers undergoing prophylactic surgery.

PMID- 18805576
TI  - Germ cell specific protein VASA is over-expressed in epithelial ovarian cancer
      and disrupts DNA damage-induced G2 checkpoint.
AB  - OBJECTIVE: Cancer cells have characteristics, such as high telomerase activity
      and high levels of migration activity and proliferation, which are very similar
      to those of germ cell lineages. In this study, we examined the expression of
      VASA, a germ cell lineage specific marker and evaluated its clinical significance
      in epithelial ovarian cancer (EOC). METHODS: We investigated VASA expression in
      75 EOC tissues by immunohistochemistry, correlating results with
      clinicopathological factors. To clarify the effects of VASA on cellular
      phenotypes, we compared the protein expression profiles between SKOV-3 cells
      stably expressing VASA (SKOV-3-VASA) and vector-control cell lines by coupling 2D
      fingerprinting and identification of proteins by mass spectrometry. RESULTS: VASA
      expression in tumor cells was found in 21 of 75 cases and was positively
      correlated with high age and serous histology. Significant down-regulation of 14
      3-3sigma was observed in SKOV-3-VASA versus control cells. Over-expression of
      VASA abrogates the G2 checkpoint, induced by DNA damage, by down-regulating the
      expression of 14-3-3sigma. CONCLUSIONS: These results suggest that VASA may
      either play a direct role in the progression of EOC or serve as a valuable marker
      of tumorigenesis.

PMID- 18805577
TI  - Toward experimental assessment of receptor occupancy: TGN1412 revisited.
AB  - In March 2006, 6 healthy volunteers experienced serious adverse reactions during
      a first-in-human clinical trial of the superagonistic anti-CD28 mAb TGN1412. A
      first investigation excluded contaminations of the drug product or protocol
      irregularities as the root cause. Later, an expert scientific group convened in
      the United Kingdom to develop recommendations pertinent to minimizing risks of
      first-in-human clinical trials. The expert scientific group concluded from in
      silico calculations that at the initial dose of 0.1 mg/kg, which was adjusted on
      the basis of the no observed adverse effect level, approximately 86.2% to 90.9%
      CD28 receptor occupancy was obtained. Here we developed a flow cytometric method
      that revealed receptor occupancy of approximately 45% to 80% under the above
      conditions. Thus we present a method to experimentally determine receptor
      occupancy that can be taken as one parameter to define the minimal anticipated
      biological effect level as the basis for calculating safer starting doses for
      first-in-human clinical trials for products in which a potential risk has been
      identified. Additional measures are being discussed that will help to
      significantly improve safety of first-in-human clinical trials.

PMID- 18805578
TI  - Dissociation between the prevalence of atopy and allergic disease in rural China
      among children and adults.
AB  - BACKGROUND: The prevalence of allergic diseases is increasing worldwide, but the
      reasons are not well understood. Previous studies suggest that this trend might
      be associated with lifestyle and urbanization. OBJECTIVE: We sought to describe
      patterns of sensitization and allergic disease in an unselected agricultural
      Chinese population. METHODS: The data were derived from a community-based twin
      study in Anqing, China. Skin prick tests were performed to foods and
      aeroallergens. Atopy was defined as sensitization to 1 or more allergens.
      Allergic disease was ascertained by means of self-report. The analysis was
      stratified by sex and age (children [11-17 years] and adults [>or=18 years]) and
      included 1059 same-sex twin pairs. RESULTS: Of 2118 subjects, 57.6% were male (n
      = 1220). Ages ranged from 11 to 71 years, and 43.3% were children (n = 918).
      Atopy was observed in 47.2% (n = 999) of participants. The most common
      sensitizing foods were shellfish (16.7%) and peanut (12.3%). The most common
      sensitizing aeroallergens were dust mite (30.6%) and cockroach (25.2%). Birth
      order and zygosity had no effect on sensitization rates. Multivariate logistic
      regression models revealed that risk factors for sensitization include age for
      foods and sex for aeroallergens. The rates of food allergy and asthma were
      estimated to be less than 1%. CONCLUSIONS: Atopic sensitization was common in
      this rural farming Chinese population, particularly to shellfish, peanut, dust
      mite, and cockroach. The prevalence of allergic disease, in contrast, was quite
      low.

PMID- 18805579
TI  - Mutations of JAK2 in acute lymphoblastic leukaemias associated with Down's
      syndrome.
AB  - BACKGROUND: Children with Down's syndrome have a greatly increased risk of acute
      megakaryoblastic and acute lymphoblastic leukaemias. Acute megakaryoblastic
      leukaemia in Down's syndrome is characterised by a somatic mutation in GATA1.
      Constitutive activation of the JAK/STAT (Janus kinase and signal transducer and
      activator of transcription) pathway occurs in several haematopoietic malignant
      diseases. We tested the hypothesis that mutations in JAK2 might be a common
      molecular event in acute lymphoblastic leukaemia associated with Down's syndrome.
      METHODS: JAK2 DNA mutational analysis was done on diagnostic bone marrow samples
      obtained from 88 patients with Down's syndrome-associated acute lymphoblastic
      leukaemia; and 216 patients with sporadic acute lymphoblastic leukaemia, Down's
      syndrome-associated acute megakaryoblastic leukaemia, and essential
      thrombocythaemia. Functional consequences of identified mutations were studied in
      mouse haematopoietic progenitor cells. FINDINGS: Somatically acquired JAK2
      mutations were identified in 16 (18%) patients with Down's syndrome-associated
      acute lymphoblastic leukaemia. The only patient with non-Down's syndrome
      associated leukaemia but with a JAK2 mutation had an isochromosome 21q. Children
      with a JAK2 mutation were younger (mean [SE] age 4.5 years [0.86] vs 8.6 years
      [0.59], p<0.0001) at diagnosis. Five mutant alleles were identified, each
      affecting a highly conserved arginine residue (R683). These mutations
      immortalised primary mouse haematopoietic progenitor cells in vitro, and caused
      constitutive Jak/Stat activation and cytokine-independent growth of BaF3 cells,
      which was sensitive to pharmacological inhibition with JAK inhibitor I. In
      modelling studies of the JAK2 pseudokinase domain, R683 was situated in an
      exposed conserved region separated from the one implicated in myeloproliferative
      disorders. INTERPRETATION: A specific genotype-phenotype association exists
      between the type of somatic mutation within the JAK2 pseudokinase domain and the
      development of B-lymphoid or myeloid neoplasms. Somatically acquired R683 JAK2
      mutations define a distinct acute lymphoblastic leukaemia subgroup that is
      uniquely associated with trisomy 21. JAK2 inhibitors could be useful for
      treatment of this leukaemia. FUNDING: Israel Trade Ministry, Israel Science
      Ministry, Jewish National Fund UK, Sam Waxman Cancer Research Foundation, Israel
      Science Foundation, Israel Cancer Association, Curtis Katz, Constantiner
      Institute for Molecular Genetics, German-Israel Foundation, and European
      Commission FP6 Integrated Project EUROHEAR.

PMID- 18805580
TI  - JAK2--a new player in acute lymphoblastic leukaemia.

PMID- 18805581
TI  - Nuclear localisation of the endocannabinoid metabolizing enzyme fatty acid amide
      hydrolase (FAAH) in invasive trophoblasts and an association with recurrent
      miscarriage.
AB  - Endocannabinoids are lipid signalling molecules that are related to the major
      psychoactive component in marijuana, delta-9-tetrahydrocannabinol and are
      increasingly recognized as being important in implantation and development of
      early embryos. The endocannabinoid anandamide, is metabolized by the enzyme fatty
      acid amide hydrolase (FAAH), and insufficient levels of this enzyme have been
      implicated in spontaneous miscarriage in women and implantation failure in mice.
      We screened placental bed biopsies and placental tissue from 45 women with
      recurrent miscarriage and 17 gestation-matched women with normal pregnancies for
      the expression of FAAH by immunohistochemistry. Unexpectedly, the enzyme appeared
      to be localised to the nucleus of trophoblasts and this was confirmed by western
      blotting of sub-cellular fractions and confocal microscopy. FAAH was expressed in
      the cytoplasm of large decidual stromal cells and significantly more women with
      recurrent miscarriage (73%) expressed FAAH in these cells than women with normal
      pregnancy (31%). FAAH was also expressed in the nucleus of extravillous
      trophoblasts that had invaded the decidua from 67% of women with recurrent
      miscarriage but was not expressed by these cells in any women with normal
      pregnancies. In contrast, FAAH was expressed in extravillous trophoblasts that
      had migrated out of the villi but that had not yet invaded the decidua in both
      normal pregnancies and in cases of recurrent miscarriage. FAAH was also present
      in the nucleus of a small number of villous trophoblasts in some specimens. FAAH
      appears to be over expressed in trophoblasts that have invaded the decidua, as
      well as in large decidual stromal cells in many cases of recurrent miscarriage.
      This may reflect inadequate control of the cannabinoid system in the uterus of
      women who experience recurrent miscarriages. The functional significance of the
      unexpected nuclear localisation of FAAH in trophoblasts is not yet clear.

PMID- 18805582
TI  - Nonhematological autoimmunity (glomerulosclerosis, paraneoplastic pemphigus and
      paraneoplastic neurological syndrome) in a patient with chronic lymphocytic
      leukemia: Diagnosis, prognosis and management.

PMID- 18805583
TI  - Results of a phase I/II British Society of Bone Marrow Transplantation study on
      PCR-based pre-emptive therapy with valganciclovir or ganciclovir for active CMV
      infection following alemtuzumab-based reduced intensity allogeneic stem cell
      transplantation.
AB  - This multi-centre randomized study assessed the bioavailability of ganciclovir in
      patients undergoing alemtuzumab-based reduced intensity conditioning (RIC)
      haematopoietic stem cell transplantation (HSCT) after oral administration of
      valganciclovir. Patients were randomized to 2 groups receiving either oral
      valganciclovir (900 mg twice daily) or intravenous ganciclovir (5mg/kg twice
      daily) for 14 days. Twenty-seven patients were recruited and 18 patients (67%)
      completed allocated treatment resulting in clearance of cytomegolovirus (CMV) DNA
      load at a median of 14 days. The bioavailability of ganciclovir from
      valganciclovir was 73% (95% CI: 34-112%). The average exposure in the
      valganciclovir group (36.9+/-14.9 microg h/ml) was higher than the ganciclovir
      cohort (27.9+/-7.5 microg h/ml). When compared with intravenous ganciclovir, oral
      valganciclovir had high bioavailability in patients undergoing alemtuzumab-based
      RIC HSCT.

PMID- 18805584
TI  - Anaplasma phagocytophilum in horses and ticks: a preliminary survey of Central
      Italy.
AB  - Anaplasma phagocytophilum, the causative agent of granulocytic ehrlichiosis,
      affects several species of wild and domesticated mammals, including horses. In
      this work we compared direct and indirect methods to evaluate A. phagocytophilum
      presence in Central Italy: 135 sera were screened by IFA for A. phagocytophilum
      and other haemopathogens (Theileria equi and Babesia caballi). Each horse was
      also tested for A. phagocytophilum 16S rRNA with a nested-PCR technique. In order
      to examine the risk of A. phagocytophilum transmission, 114 ticks were examined
      for the presence of A. phagocytophilum by PCR targeting the 16S rRNA. The
      seroprevalence against A. phagocytophilum was 17.03% and 11 horses (8.14%) showed
      positive PCR results. The concordance rate of A. phagocytophilum detection
      between IFAT and PCR had a K value of 0.34.

PMID- 18805585
TI  - Wildlife (Boselaphus tragocamelus)-small ruminant (goat and sheep) interface in
      the transmission of 'Bison type' genotype of Mycobacterium avium subspecies
      paratuberculosis in India.
AB  - Information on Mycobacterium avium subspecies paratuberculosis (MAP) genotypes
      infecting different animal species in India is limited. Presence of MAP was
      investigated in free ranging antelopes (locally known as Nilgai/blue
      bulls/Boselaphus tragocamelus) using direct microscopy, culture, IS900 PCR and
      IS1311 PCR-REA. IS900 elements of MAP from Nilgai and previously isolated from
      goats were sequenced and compared to establish inter-species transmission between
      free ranging Nilgai and closed farm herds and flocks of goats and sheep sharing
      common grazing and water resources. Fecal samples were collected from two
      geographical regions (Mathura and Kanpur Dehat districts) separated by 300km, in
      North India. Of the 42 fecal samples cultured, MAP colonies were recovered from
      23.8% samples (Nilgai). Of the 10 positive fecal samples, two were in 'Super
      shedder' (>1000cfu/g) category and rest were moderate (<10-100cfu/g) shedders.
      None of the Nilgai from Kanpur Dehat was positive in culture. The 229bp fragment
      targeting specific IS900 sequence was amplified from template DNA isolated from
      all the positive MAP cultures of Nilgai. Using IS1311 PCR-REA, MAP colonies were
      genotyped as 'Bison type'. Goatherds and a sheep flock located at Central
      Institute for Research on Goats (CIRG), shared 303.52ha of land (Mathura district
      of Uttar Pradesh) with Nilgai and were endemic for MAP infection. MAP strains
      isolated from goats and sheep have been genotyped as 'Bison type'. Nucleotide
      sequence of the insertion elements (900) from MAP 'Bison type' strain (S5) of
      goat origin and MAP (B42) from Nilgai showed difference of 2 (1%) base pairs at
      the 11th and 12th position (Genbank accession number EU130943). Study is first
      report on sharing (inter-species transmission) of a new 'Bison type' genotype of
      MAP between free ranging wildlife (Nilgai population) and domestic animals (farm
      goatherds and sheep flocks) in India.

PMID- 18805586
TI  - Molecular characterization of IRF3 and IRF7 in rainbow trout, Oncorhynchus
      mykiss: functional analysis and transcriptional modulation.
AB  - Interferon regulatory factors (IRF) 3 and 7 in mammals are known to be crucial in
      regulating the type I interferon (IFN) response to viral infection as part of
      transcriptional complexes binding to IRF-binding elements (IRF-Es) and interferon
      stimulatory response elements (ISREs) within IFN and interferon-stimulated genes
      (ISGs). Here we report the sequencing and characterization of full-length cDNA
      homologues of rainbow trout (rt)IRF7 and, for the first time in fish, IRF3.
      RtIRF3 consists of 2127 bp with a 159 bp 5'-UTR-containing two upstream AUGs and
      a 573 bp 3'-UTR. RtIRF7 was found to be 2055 bp, with a 102 bp 5'-UTR and a 705
      bp 3'-UTR. The open reading frames (ORFs) translate into 464 amino acid and 415
      amino acid proteins, respectively, each possessing a putative DNA-binding domain
      (DBD) containing a tryptophan cluster, which is characteristic of all IRF family
      members. The presence of putative IRF association domain (IAD)s, serine-rich C
      terminal domains (poorly conserved in trout IRF3), and phylogenetic analysis
      places the two genes in the IRF3 subfamily. Both genes were found to be
      upregulated by poly I:C, type I recombinant rainbow trout (r) IFN (second
      isoform, type I rIFN), type II rIFN (rIFNgamma), LPS, and rIL-1beta in the trout
      macrophage cell line, RTS-11. Poly I:C and type I rIFN also induced IRF3 and IRF7
      expression in a trout fibroblast cell line (RTG-2). Transient transfection of RTG
      2 cells with each IRF fused to GFP revealed a predominant cytoplasmic
      distribution found most intensely around the nucleus and, to a lesser extent,
      within cell nuclei. Transient transfection of rtIRF3 in the Mx-1-luciferase
      reporter cell line, RTG-P1, revealed a modest increase in luciferase activity
      relative to the vehicle control, which was lost in cells over-expressing a DBD
      truncated form of rtIRF3. Both full-length and DBD-truncated forms of rtIRF7
      increased reporter activity relative to the control, although to a non
      significant extent. Electromobility shift assays (EMSAs) did not reveal a
      specific interaction between each IRF and the ISRE element found in the Mx-1
      promoter, although the Mx-1 ISRE bound specifically to endogenous transcriptional
      complexes. These data support the premise that rtIRF3 and rtIRF7 are important
      molecules in the regulation of antiviral responses in fish, with the impact of
      rIFNgamma on rtIRF3/7 expression implying a role for these IRFs in immune
      processes other than type I IFN-driven antiviral responses.

PMID- 18805587
TI  - Coordination changes and auto-hydroxylation of FIH-1: uncoupled O2-activation in
      a human hypoxia sensor.
AB  - Hypoxia sensing is the generic term for pO2-sensing in humans and other higher
      organisms. These cellular responses to pO2 are largely controlled by enzymes that
      belong to the Fe(II) alpha-ketoglutarate (alphaKG) dependent dioxygenase
      superfamily, including the human enzyme called the factor inhibiting HIF (FIH-1),
      which couples O2-activation to the hydroxylation of the hypoxia inducible factor
      alpha (HIFalpha). Uncoupled O2-activation by human FIH-1 was studied by exposing
      the resting form of FIH-1 (alphaKG + Fe)FIH-1, to air in the absence of HIFalpha.
      Uncoupling lead to two distinct enzyme oxidations, one a purple chromophore
      (lambda(max) = 583 nm) arising from enzyme auto-hydroxylation of Trp296, forming
      an Fe(III)-O-Trp296 chromophore [Y.-H. Chen, L.M. Comeaux, S.J. Eyles, M.J.
      Knapp, Chem. Commun. (2008), doi:10.1039/B809099H]; the other a yellow
      chromophore due to Fe(III) in the active site, which under some conditions also
      contained variable levels of an oxygenated surface residue (oxo)Met275. The
      kinetics of purple FIH-1 formation were independent of Fe(II) and alphaKG
      concentrations, however, product yield was saturable with increasing [alphaKG]
      and required excess Fe(II). Yellow FIH-1 was formed from (succinate+Fe)FIH-1, or
      by glycerol addition to (alphaKG+Fe)FIH-1, suggesting that glycerol could
      intercept the active oxidant from the FIH-1 active site and prevent
      hydroxylation. Both purple and yellow FIH-1 contained high-spin, rhombic Fe(III)
      centers, as shown by low temperature EPR. XAS indicated distorted octahedral
      Fe(III) geometries, with subtle differences in inner-shell ligands for yellow and
      purple FIH-1. EPR of Co(II)-substituted FIH-1 (alphaKG + Co)FIH-1, indicated a
      mixture of 5-coordinate and 6-coordinate enzyme forms, suggesting that resting
      FIH-1 can readily undergo uncoupled O2-activation by loss of an H2O ligand from
      the metal center.

PMID- 18805588
TI  - Fusobacterial infections: clinical spectrum and incidence of invasive disease.
AB  - OBJECTIVES: Clinically significant infections caused by members of the genus
      Fusobacterium are rare. We sought to describe the spectrum of clinical disease
      and epidemiology of these conditions presenting to an acute hospital over a five
      year period. METHODS: Clinical records relating to consecutive laboratory
      isolates of Fusobacterium species were reviewed and cases classified according to
      pre-specified definitions of primary site and invasive infection. RESULTS: 78
      Fusobacterium isolates were identified, 25 of which were associated with invasive
      disease, most commonly in men (76% of cases). Invasive Fusobacterium necrophorum
      infection of the head and neck was not observed in patients over 50. Invasive
      intra-abdominal disease was not observed amongst those under 60. 2 cases of
      Fusobacterium nucleatum bacteraemia were identified in neutropenic children. One
      retroperitoneal abscess may have represented secondary infection due to
      periodontitis. Obstetric infections were the most common clinical syndromes
      associated with isolates from the female genital tract. The incidence of invasive
      head and neck disease in the population aged 15-50 was 6.7 per million/year.
      There were no deaths. CONCLUSIONS: Invasive fusobacterial infections are rare,
      affect distinct patient groups and are associated with good clinical outcomes in
      the majority of cases.

PMID- 18805589
TI  - Blood pressure and white matter integrity in geriatric depression.
AB  - BACKGROUND: Cerebrovascular disease may increase vulnerability to geriatric
      depression, a syndrome often accompanied by frontal-subcortical lesions. High
      blood pressure is a risk factor for cerebrovascular disease and white matter
      changes. This study examined whether and in which brain regions blood pressure is
      associated with compromised white matter integrity in elderly depressed patients.
      METHODS: We studied the association between blood pressure and white matter
      integrity assessed by diffusion tensor imaging (fractional anisotropy, FA) in 41
      older patients with major depression. Correlations between FA and blood pressure,
      after controlling for age, were examined with a voxelwise analysis. RESULTS:
      Significant associations between FA and blood pressure were detected throughout
      the anterior cingulate and in multiple frontostriatal and frontotemporal regions.
      LIMITATIONS: This study did not employ a healthy control group. Moreover, the
      relatively small sample size precluded a comparison of patients with and without
      hypertension. CONCLUSIONS: Compromised frontal-striatal white matter integrity
      may be the anatomical background through which blood pressure confers
      vulnerability to depression.

PMID- 18805590
TI  - Eighteen months of drug treatment for depression: predicting relapse and
      recovery.
AB  - BACKGROUND: The clinically relevant outcomes in treating depression are
      persistent recovery, relapse, and treatment resistance. METHOD: 175 outpatients
      treated with antidepressants for 6 months were assessed for major depression.
      Those who had recovered were prospectively monitored for one year to study rates
      of relapse (at least two weeks of major depression). Those who were depressed at
      6 months were monitored for rates of recovery (at least 8 weeks of no major
      depression). RESULTS: 94% of the sample was monitored for one year. Of the 123
      patients who were not depressed at 6 months 57 (46%) relapsed. Patients who
      relapsed were more likely to have a history of recurrent depression, to have
      residual depressive symptoms, to have a less sustained response to initial
      treatment, to have avoidant personality disorder symptoms, schizotypal
      personality disorder symptoms, higher harm avoidance (HA) scores and lower self
      directedness (SD) scores. Of the 38 patients who were depressed at 6 months 13
      (34%) recovered. There were no patient characteristics associated with recovery.
      LIMITATIONS: The findings apply to moderately depressed outpatients. There was no
      placebo control. CONCLUSION: Most patients with depression will recover but many
      become unwell again within a year. Clinically long term monitoring and sustained
      efforts to treat patients with major depression seem warranted.

PMID- 18805591
TI  - Platelet aggregation and TGF-beta(1) plasma levels in pregnant women with
      preeclampsia.
AB  - OBJECTIVES: Platelets and transforming growth factor-beta(1) (TGF-beta(1)) are
      thought to be involved in the pathogenesis of preeclampsia. Our objectives were
      to determine plasma concentration of TGF-beta(1) in normotensive and preeclamptic
      women in the third trimester of pregnancy and to evaluate the correlation of TGF
      beta(1) plasma levels with platelet count and agonist-induced aggregation
      capacity. METHODS: Thirty-three women with preeclampsia were compared with 36
      healthy women with uncomplicated pregnancies. Peripheral venous blood samples
      were obtained, and TGF-beta(1) plasma levels measured by an enzyme-linked
      immunoassay. Platelet aggregation was induced by the agonist agents adenosine
      diphosphate (ADP), collagen and epinephrine, and was determined in platelet-rich
      plasma by aggregometry. RESULTS: Plasma concentrations of active TGF-beta(1) were
      significantly higher in preeclamptic women (10.41+/-2.07ng/mL) compared with
      normotensive pregnant women (7.01+/-3.29ng/mL). Platelet number and platelet
      agonist-induced aggregation percent were significantly lower in patients with
      preeclampsia than in healthy pregnant women. A significant correlation was
      observed between TGF-beta(1) plasma levels and platelet agonist-induced
      aggregation percent as between plasma levels of TGF-beta(1) and platelet number
      in preeclamptic patients. CONCLUSION: The association between impairment in
      platelet responsiveness and higher levels of TGF-beta(1) in the plasma of
      patients with preeclampsia suggests that this cytokine may play a role in the
      pathophysiological events of preeclampsia that are dependent on platelet
      activation.

PMID- 18805592
TI  - Maternal and fetal C-reactive protein genotype and first trimester CRP
      concentrations in maternal plasma.
AB  - Maternal plasma CRP concentrations in pregnancy are increased over pre-pregnancy
      values and high concentrations have been associated with adverse obstetrical
      outcomes. The objective of this study was to explore the relationship between
      maternal and fetal variation in C-reactive protein (CRP) genotype and maternal
      plasma CRP concentrations in the first trimester in low risk patients. DNA was
      extracted from maternal and cord blood of subjects in a prospective observational
      cohort. Single-nucleotide polymorphism (SNP) selection was made using a linkage
      disequilibrium bin approach. CRP concentrations were measured in first trimester
      maternal plasma using an enzyme-linked immunosorbent assay (ELISA) kit. Kruskal
      Wallis rank testing was used to analyze genetic and clinical determinants of CRP
      concentrations. Genotype results were available in 190 mother-baby pairs. There
      was no significant difference in CRP concentration among maternal or fetal CRP
      genotypes. Thus, first trimester concentrations of maternal plasma CRP in low
      risk subjects do not appear to be significantly associated with CRP genotype.
      Instead, differences in clinical factors probably have more influence on baseline
      maternal CRP concentrations.

PMID- 18805593
TI  - Langerhans cells in porcine skin.
AB  - Langerhans cells (LCs) are resident dendritic cells (DCs) of skin and mucosal
      epithelium. The standard for identifying skin DCs as LCs is expression of
      langerin (CD207), a surface protein that mediates Birbeck granule (BG) formation
      upon internalization. Reports of BGs in porcine skin DC are contradictory, due to
      lack of langerin detection. Here, we present the sequence of porcine
      langerin/CD207, showing that the predicted porcine protein shares 75%/86% amino
      acid identity/similarity with human. Langerin mRNA was detected in porcine skin
      DCs by PCR and langerin protein was detected in both isolated skin DCs and skin
      sections by immunostaining. Approximately, 50-70% of skin DCs expressed langerin,
      demonstrating that the majority of porcine skin DCs are LCs. The full length
      sequence combined with the identification of antibodies reactive with porcine
      langerin, facilitates the study of LCs in swine, and advances the use of swine
      for studying skin diseases and infectious disease processes involving skin.

PMID- 18805595
TI  - Cochlear implantation in patients with Jervell and Lange-Nielsen syndrome, and a
      review of literature.
AB  - Jervell and Lange-Nielsen syndrome is characterized by a long QT interval in
      electrocardiography, syncopal attacks and congenital sensorineural hearing loss.
      Upon diagnosis, beta-blockers is recommended as the first choice of medication,
      which is considered to reduce the occurrence rate of syncopal attack and sudden
      death during life. Cochlear implantation is indicated for hearing rehabilitation
      in this syndrome with profound deafness. The auditory and language outcome after
      cochlear implantation in this syndrome is not worse than those in patients with
      non-syndromic sensorineural deafness. The life quality in this syndrome could be
      improved greatly with cochlear implantation only if the cardiologic event has
      been controlled effectively.

PMID- 18805594
TI  - MHC class II exacerbates demyelination in vivo independently of T cells.
AB  - We have shown previously the importance of MHC class II for central nervous
      system remyelination; however, the function of MHC class II during cuprizone
      induced demyelination has not been examined. Here, we show that I-A(beta)-/- mice
      exhibit significantly reduced inflammation and demyelination. RAG-1(1/1) mice are
      indistinguishable from controls, indicating T cells may not play a role. The role
      of MHC class II depends on an intact cytoplasmic tail that leads to the
      production of IL-1beta, TNF-alpha, and nitric oxide, and oligodendrocyte
      apoptosis. Thus, the function of MHC class II cytoplasmic tail appears to
      increase microglial proliferation and activation that exacerbates demyelination.

PMID- 18805596
TI  - Body-temperature maintenance as the predominant function of the vanilloid
      receptor TRPV1.
AB  - Agonists of the transient receptor potential vanilloid type 1 (TRPV1), such as
      capsaicin, cause pain and a drop in body temperature (hypothermia). Conversely,
      antagonists of TRPV1 block pain behaviors in rodent models of inflammation,
      osteoarthritis and cancer. Efforts that evaluate TRPV1 antagonists in on-target
      challenge models have uncovered that TRPV1 blockade elicits an increase in body
      temperature (hyperthermia) from rodents to primates, revealing the intimate
      relationship between the role of TRPV1 in pain and body-temperature maintenance.
      This evolutionarily conserved function of TRPV1 in body-temperature maintenance
      became a hurdle for clinical development of one antagonist, AMG 517. However,
      several other TRPV1 antagonists are currently being evaluated in the clinic and
      soon-to-be-published results should shed light on the potential of managing
      antagonist-induced hyperthermia while developing them as therapeutics.

PMID- 18805597
TI  - Kounis syndrome: a manifestation of drug-eluting stent thrombosis associated with
      allergic reaction to contrast material.
AB  - Stent components acting as potential antigens and promoting intracoronary mast
      cell activation can lead to catastrophic intrastent thrombosis. Patients with
      drug-eluting stent (DES) implantation are prone to hypersensitivity reactions
      from five potential antigens namely, nickel strut, polymer coating, eluted drug,
      as well as, concomitant drugs clopidogrel and aspirin. These events may be more
      common than suspected because it is hard to document them, unless they become
      systemic, in which case they manifest themselves as the Kounis syndrome
      characterized by the concurrence of acute coronary events with hypersensitivity
      reactions. This report concerns of a patient with implanted DES who developed an
      acute myocardial infarction in the stent area following an allergic reaction to
      contrast material.

PMID- 18805598
TI  - Adaptive servo-ventilation in heart failure patients with sleep apnea: a real
      world study.
AB  - BACKGROUND: Congestive heart failure (CHF) patients often present with
      obstructive and central sleep apnea occurring concurrently within the same night.
      This study assessed the efficacy of, and improvements associated with, the use of
      adaptive servo-ventilation (ASV) in CHF patients with all types of sleep apnea.
      We hypothesized that ASV would be effective at reducing sleep apnea and improving
      both cardiac status and quality of life. METHODS: Eleven male patients with
      stable CHF and sleep apnea (apnea/hypopnea index (AHI) >15 events/h) were treated
      with 6 months optimized ASV and compared to 8 patients not receiving ASV. At
      baseline, both groups were comparable for New York Heart Association class, left
      ventricular ejection fraction (LVEF), plasma Brain Natriuretric Peptide (BNP)
      concentrations and AHI. All patients were receiving optimal medical therapy.
      RESULTS: At 6 months ASV significantly reduced AHI (mean (SD), baseline 49.0
      (35.1) v ASV 7.6 (14.6); p=0.001) and LVEF was increased (median (inter-quartile
      range), treatment group: +5.7 (1.6-9.5) v comparison group: -4.0 (-8.9-+4.6)%
      respectively; p=0.04) but not BNP (p=0.59). The energy/vitality score of the SF
      36 quality of life questionnaire was also improved at 6 months (treatment group:
      +10 (5-35) v comparison group: -12 (-18-+10); p=0.005). CONCLUSION: ASV
      effectively reduces all types of sleep apnea. Six months of use is associated
      with improvement in LVEF and aspects of quality of life.

PMID- 18805599
TI  - Increase in coronary blood flow by intra-aortic balloon counterpulsation in a
      porcine model of myocardial reperfusion.
AB  - BACKGROUND: Studies of the IABP have reported variable effects on coronary blood
      flow (CBF). The purpose of the present study was to measure the changes in
      coronary blood flow induced by intra-aortic balloon pump (IABP) counterpulsation
      in normal and reperfused porcine myocardium. METHODS: A 30-ml IABP was placed in
      the descending aorta of 6 open-chest pigs. Each pig underwent occlusion of the
      mid-left anterior descending (LAD) coronary artery for 1 h, followed by
      reperfusion for 2 h. The effects of IABP support on systolic aortic pressure
      (SAP) and aortic end-diastolic pressure were recorded. The mean CBF, distal to
      the LAD occlusion site was measured at baseline and during reperfusion, with and
      without IABP counterpulsation. RESULTS: The IABP decreased SAP and aortic end
      diastolic pressure in normal and reperfused myocardium, and maintained a peak
      aortic diastolic augmentation at the level of SAP. In normal myocardium, the IABP
      decreased mean CBF by 8.4+/-2.2% (p<0.001). At 2, 15, 30, 60, 90 and 120 min of
      reperfusion, the IABP increased mean CBF by 11.5+/-6.8%, 8.0+/-7.0%, 11.2+/-6.9%,
      12.4+/-12.9%, 23.5+/-9.9% and 8.9+/-6.9%, of the corresponding value without the
      assistance of the IABP (all p<0.05). CONCLUSIONS: In the normal heart, IABP
      counterpulsation decreased CBF, probably because of a decrease in myocardial
      oxygen demand from a decreased afterload. During reperfusion the IABP increased
      CBF, suggesting that it might effectively mitigate the no-reflow phenomenon.

PMID- 18805600
TI  - Improving quantitative exposure assessment by considering genetic diversity of B.
      cereus in cooked, pasteurised and chilled foods.
AB  - The natural contamination of foods with a bacterial pathogen frequently consists
      of a mixture of strains with their own characteristics of survival, growth
      potential and virulence. Quantitative Microbial Risk Assessment (QMRA) must
      account for this genetic diversity to reflect the variability of the pathogen
      risk and to identify the genetic groups present at key stages of the food
      pathway. To describe the transmission dynamics of a heterogeneous population of
      B. cereus, we developed an exposure model that covers a food processing chain
      from "farm to table". The studied food was a cooked, pasteurised and chilled
      courgette puree used as an example of Refrigerated Processed Food of Extended
      Durability (REPFED). The B. cereus population consists of a continuum of genetic
      groups ranging from mesophilic and highly heat resistant, to psychrotrophic and
      moderately-heat resistant ones. At each step in a processing chain comprising
      cooking, blending, mixing with ingredients providing a secondary contamination,
      pasteurisation and chilling for several weeks, the prevalence of contaminated
      units (batches or packages) and the spore load within the units was determined
      for each genetic group, as well as their proportion to the total B. cereus
      population in the units. The model predicted that all packages contain mesophilic
      groups just after partitioning. The addition of mesophilic strains by the
      ingredients during the process of the courgette puree was an important
      contribution. At the end of the domestic storage, the model predicted a dominance
      of the mesophilic groups, while only some psychrotrophic groups were present.

PMID- 18805601
TI  - Direct costs associated with the disease management of patients with unresectable
      advanced non-small-cell lung cancer in The Netherlands.
AB  - INTRODUCTION: Disease management and costs of treatment of patients with
      unresectable advanced non-small-cell lung cancer (NSCLC) in The Netherlands are
      not well known. METHODS: A retrospective medical chart review was performed by
      collecting data from the time of diagnosis until the time of death or the end of
      the evaluation period. In addition to the demographic data, information was
      collected on the overall management of the patient. Hospital resource utilisation
      data collected included number of outpatient specialist visits, number and length
      of hospitalisation, type and number of diagnostic and laboratory procedures, type
      and number of radiotherapy cycles and detailed information on chemotherapy. To
      evaluate the economic impact of second-line treatment, a distinction was made
      between patients who received only best supportive care (BSC, group A) and those
      who received chemotherapy as a second-line treatment in addition to BSC (group
      B). The study was performed from the hospital perspective and reports on 2005
      costs. RESULTS: Of 102 patients, 74 belonged to group A and 28 to group B.
      Patient management included a multidisciplinary approach, the extent of which
      depended on symptoms of the disease and presence of metastases. The average total
      treatment cost per patient per year of unresectable advanced NSCLC in The
      Netherlands was euro32,840 in group A and euro31,187 in group B. In both groups,
      hospitalisation was the major cost driver. In group B second-line chemotherapy
      was the second largest contributor of the costs. In spite of the difference in
      numbers of treatment lines provided to patients in groups A and B the total
      average costs per patient per year were comparable. Overall, the management of
      unresectable advanced NSCLC appeared to conform with current guidelines in The
      Netherlands. CONCLUSION: These patients show high medical resource consumption,
      with hospitalisation being the main cost driver in both groups. As economic
      arguments are becoming increasingly important in medical decision making on both
      national and local levels, this information is relevant for both policy makers
      and specialists. These data can also be used in future research to evaluate the
      economic impact of new therapies in NSCLC, especially of those that aim to treat
      patients in an outpatient setting.

PMID- 18805602
TI  - Obtaining the porewater composition of a clay rock by modeling the in- and out
      diffusion of anions and cations from an in-situ experiment.
AB  - A borehole in the Callovo-Oxfordian clay rock in ANDRA's underground research
      facility was sampled during 1 year and chemically analyzed. Diffusion between
      porewater and the borehole solution resulted in concentration changes which were
      modeled with PHREEQC's multicomponent diffusion module. In the model, the clay
      rock's pore space is divided in free porewater (electrically neutral) and diffuse
      double layer water (devoid of anions). Diffusion is calculated separately for the
      two domains, and individually for all the solute species while a zero-charge flux
      is maintained. We explain how the finite difference formulas for radial diffusion
      can be translated into mixing factors for solutions. Operator splitting is used
      to calculate advective flow and chemical reactions such as ion exchange and
      calcite dissolution and precipitation. The ion exchange reaction is formulated in
      the form of surface complexation, which allows distributing charge over the fixed
      sites and the diffuse double layer. The charge distribution affects pH when
      calcite dissolves, and modeling of the experimental data shows that about 7% of
      the cation exchange capacity resides in the diffuse double layer. The model
      calculates the observed concentration changes very well and provides an estimate
      of the pristine porewater composition in the clay rock.

PMID- 18805603
TI  - An aqueous gel fixed combination of clindamycin phosphate 1.2% and benzoyl
      peroxide 2.5% for the once-daily treatment of moderate to severe acne vulgaris:
      assessment of efficacy and safety in 2813 patients.
AB  - OBJECTIVE: We sought to evaluate efficacy, safety, and tolerability of a
      combination of clindamycin phosphate 1.2% and benzoyl peroxide 2.5% (clindamycin
      BPO 2.5%) aqueous gel in moderate to severe acne vulgaris. METHODS: A total of
      2813 patients, aged 12 years or older, were randomized to receive clindamycin-BPO
      2.5%, individual active ingredients, or vehicle in two identical, double-blind,
      controlled 12-week, 4-arm studies evaluating safety and efficacy (inflammatory
      and noninflammatory lesion counts) using Evaluator Global Severity Score and
      subject self-assessment. RESULTS: Clindamycin-BPO 2.5% demonstrated statistical
      superiority to individual active ingredients and vehicle in reducing both
      inflammatory and noninflammatory lesions and acne severity. Visibly greater
      improvement was observed by patients with clindamycin-BPO 2.5% as early as week
      2. No substantive differences were seen in cutaneous tolerability among treatment
      groups and less than 1% of patients discontinued treatment because of adverse
      events. LIMITATIONS: Data from controlled studies may differ from clinical
      practice. CONCLUSIONS: Clindamycin-BPO 2.5% provides statistically significant
      greater efficacy than individual active ingredients and vehicle with a highly
      favorable safety and tolerability profile.

PMID- 18805604
TI  - Cardiovascular risk and memory in non-demented elderly women.
AB  - OBJECTIVE: To determine whether cardiovascular (CV) risk is associated with
      subtle memory deficits in non-demented, healthy older women with a family history
      of Alzheimer disease (AD). METHODS: Baseline data of 375 participants from a
      randomized, double-blind placebo-controlled primary prevention trial to test the
      efficacy of hormone replacement therapy in delaying AD and cognitive decline were
      analyzed. All subjects were women over 65 with a family history of AD who had
      normal cognition and no active heart disease at baseline. A baseline memory
      composite score was calculated, consisting of immediate and delayed recall of
      verbal and nonverbal material. Multiple linear regression was performed to
      examine the association of relative CV risk with memory functioning; age,
      ethnicity and education level were included as covariates. RESULTS: Mean baseline
      memory composite score was significantly higher in those with low relative CHD
      risk than those with high relative CHD risk. CONCLUSION: These findings suggest
      that subtle elevation of CHD risk may negatively affect memory functioning even
      in otherwise healthy, non-demented older women without a history of heart
      disease.

PMID- 18805605
TI  - Stent repair of an anastomotic pseudoaneurysm of the carotid artery after free
      fibula transplantation.
AB  - We describe an anastomotic pseudoaneurysm of the carotid artery as a complication
      after free fibular transplantation. The treatment of choice was endovascular
      placement of a stent, although this could have occluded the arterial supply to
      the graft. In our case, the graft remained vital.

PMID- 18805606
TI  - Gap arthroplasty combined with distraction osteogenesis in the treatment of
      unilateral ankylosis of the temporomandibular joint and micrognathia.
AB  - Our aim was to evaluate the efficacy of simultaneous gap arthroplasty and
      distraction osteogenesis (DO) in the treatment of unilateral ankylosis of the
      temporomandibular joint (TMJ) in patients with micrognathia. During the period
      January 2000-December 2006, 11 patients with unilateral ankylosis of the TMJ and
      micrognathia were treated with simultaneous gap arthroplasty, mandibular
      osteotomy, and implantation of a distractor. Mouth opening exercises were started
      on the first postoperative day and distraction on the fifth postoperative day.
      All patients had satisfactory mouth opening at follow-up, the mean (range) being
      32.4 (28-37) mm in 13 to 58 months' follow-up. Mean length (range) of the
      mandibular body increased by DO was 12.4 (7-15) mm. Facial asymmetry was
      corrected and satisfactory occlusions achieved with the help of postoperative
      orthodontic treatment. We conclude that DO and gap arthroplasty can be used
      simultaneously in the treatment of patients with ankylosis of the TMJ and
      micrognathia.

PMID- 18805607
TI  - Total fluorine, extractable organic fluorine, perfluorooctane sulfonate and other
      related fluorochemicals in liver of Indo-Pacific humpback dolphins (Sousa
      chinensis) and finless porpoises (Neophocaena phocaenoides) from South China.
AB  - The concentrations of 10 PFCs (perfluorinated compounds: PFOS, PFHxS, PFOSA, N
      EtFOSA, PFDoDA, PFUnDA, PFDA, PFNA, PFOA, and PFHpA) were measured in liver
      samples of Indo-Pacific humpback dolphins (Sousa chinensis) (n=10) and finless
      porpoises (Neophocaena phocaenoides) (n=10) stranded in Hong Kong between 2003
      and 2007. PFOS was the dominant PFC in the tissues at concentrations ranging at
      26-693 ng/g ww in dolphins and 51.3-262 ng/g ww in porpoises. A newly developed
      combustion ion chromatography for fluorine was applied to measure total fluorine
      (TF) and extractable organic fluorine (EOF) in these liver samples to understand
      PFC contamination using the concept of mass balance analysis. Comparisons between
      the amounts of known PFCs and EOF in the livers showed that a large proportion
      (approximately 70%) of the organic fluorine in both species is of unknown origin.
      These investigations are critical for a comprehensive assessment of the risks of
      these compounds to humans and other receptors.

PMID- 18805608
TI  - Acquired Gitelman syndrome in a patient with primary Sjogren syndrome.
AB  - Acquired Gitelman syndrome (GS) associated with Sjogren syndrome (SS) is rare,
      and the test to determine the pathophysiological state of acquired GS in patients
      with primary SS has not been reported previously. A 47-year-old woman with sicca
      complex presented to our clinic with intermittent muscle cramping and weakness
      involving both lower extremities over several months. Laboratory findings showed
      hypokalemic metabolic alkalosis, hypomagnesemia, and hypocalciuria, which met the
      criteria for GS. Diagnostic evaluation identified primary SS as the cause of the
      acquired GS. Light microscopic examination of renal tissue from the patient
      showed mild tubulointerstitial nephritis. Immunohistochemical staining of renal
      tissue showed the absence of the sodium-chloride cotransporter (NCCT) in the
      distal convoluted tubules. Incubation of the patient's serum with normal mouse
      kidney tissue showed a pattern of NCCT in the distal convoluted tubules similar
      to that of incubation of normal mouse kidney with the rabbit polyclonal anti-NCCT
      antibody. This is a rare case of acquired GS associated with primary SS, and our
      findings suggest the presence of circulating autoantibodies to NCCT.

PMID- 18805609
TI  - Associations of dialysis modality and infectious mortality in incident dialysis
      patients in Australia and New Zealand.
AB  - BACKGROUND: The aim of the present investigation is to compare rates, types,
      causes, and timing of infectious death in incident peritoneal dialysis (PD) and
      hemodialysis (HD) patients in Australia and New Zealand. STUDY DESIGN:
      Observational cohort study using the Australian and New Zealand Dialysis and
      Transplant Registry data. SETTING & PARTICIPANTS: The study included all patients
      starting dialysis therapy between April 1, 1995, and December 31, 2005.
      PREDICTOR: Dialysis modality. OUTCOMES & MEASUREMENTS: Rates of and time to
      infectious death were compared by using Poisson regression, Kaplan-Meier, and
      competing risks multivariate Cox proportional hazards model analyses. RESULTS:
      21,935 patients started dialysis therapy (first treatment PD, n = 6,020; HD, n =
      15,915) during the study period, and 1,163 patients (5.1%) died of infectious
      causes (PD, 529 patients; 7.6% versus HD, 634 patients; 4.2%). Incidence rates of
      infectious mortality in PD and HD patients were 2.8 and 1.7/100 patient-years,
      respectively (incidence rate ratio PD versus HD, 1.66; 95% confidence interval
      [CI], 1.47 to 1.86). After performing competing risks multivariate Cox analyses
      allowing for an interaction between time on study and modality because of
      identified nonproportionality of hazards, PD consistently was associated with
      increased hazard of death from infection compared with HD after 6 months of
      treatment (<6 months hazard ratio [HR], 1.08; 95% CI, 0.76 to 1.54; 6 months to 2
      years HR, 1.31; 95% CI, 1.09 to 1.59; 2 to 6 years HR, 1.51; 95% CI, 1.26 to
      1.80; >6 years HR, 2.76; 95% CI, 1.76 to 4.33). This increased risk of infectious
      death in PD patients was largely accounted for by an increased risk of death
      caused by bacterial or fungal peritonitis. LIMITATIONS: Patients were not
      randomly assigned to their initial dialysis modality. Residual confounding and
      coding bias could not be excluded. CONCLUSIONS: Dialysis modality selection
      significantly influences risks, types, causes, and timing of fatal infections
      experienced by patients with end-stage kidney disease in Australia and New
      Zealand.

PMID- 18805610
TI  - Acute hepatitis B infection in a long-term hemodialysis patient despite
      persistent natural immunity.
AB  - Hepatitis B infections are a distinct clinical problem in hemodialysis patients.
      Naturally acquired antibodies from a prior hepatitis B virus infection generally
      are considered to be immunoprotective for subsequent infections. We describe a
      new-onset hepatitis B virus infection in a hemodialysis patient despite
      persistent protective levels of naturally acquired antibodies to hepatitis B
      surface antigen. This case emphasizes that the immune response to hepatitis B
      virus is complex and still poorly understood. Current recommended screening
      guidelines may be incomplete in addressing acute hepatitis B virus infections in
      hemodialysis patients. Aggressive vaccination strategies should be considered to
      maintain immunity in patients at high risk of seroconversion. Stricter
      surveillance and use of modern virus detection assays may be required to detect
      subtle infections and minimize the risk of transmission of hepatitis B virus in
      hemodialysis units.

PMID- 18805611
TI  - Recurrent atypical hemolytic uremic syndrome associated with factor I mutation in
      a living related renal transplant recipient.
AB  - Atypical hemolytic uremic syndrome, or the nondiarrheal form of hemolytic uremic
      syndrome, is a rare disorder typically classified as familial or sporadic. Recent
      literature has suggested that approximately 50% of patients have mutations in
      factor H (CFH), factor I (CFI), or membrane cofactor protein (encoded by CD46).
      Importantly, results of renal transplantation in patients with mutations in
      either CFH or CFI are dismal, with recurrent disease leading to graft loss in the
      majority of cases. We describe an adult renal transplant recipient who developed
      recurrent hemolytic uremic syndrome 1 month after transplantation. Bidirectional
      sequencing of CFH, CFI, and CD46 confirmed that the patient was heterozygous for
      a novel missense mutation, a substitution of a serine reside for a tyrosine
      residue at amino acid 369, in CFI. This report reemphasizes the importance of
      screening patients with atypical hemolytic uremic syndrome for mutations in these
      genes before renal transplantation and shows the challenges in the management of
      these patients.

PMID- 18805612
TI  - Induction of heme oxygenase-1 and ferritin in the kidney in warm antibody
      hemolytic anemia.
AB  - Warm antibody autoimmune hemolytic anemia usually is associated with
      extravascular hemolysis. We report a case of a 42-year-old man with sustained and
      moderately severe warm antibody autoimmune hemolytic anemia, hemoglobinuria,
      hemosiderinuria, and acute kidney injury. We show marked induction of heme
      oxygenase-1 and increased ferritin expression in renal tubules, along with
      increased iron deposition in renal proximal tubules. These findings in this
      clinical case thus recapitulate those observed in experimental models of heme
      protein-induced kidney injury in which a coupled induction of heme oxygenase-1
      and ferritin occurs in the kidney. We discuss the pathobiological significance of
      these findings and suggest that this linked response confers cytoprotection to
      the kidney exposed to hemoglobin and mitigates the severity of acute kidney
      injury that may otherwise occur. Finally, this case report documents that
      nephrotic-range proteinuria can occur in patients with autoimmune hemolytic
      anemia complicated by hemoglobinuria.

PMID- 18805613
TI  - Thrombotic microangiopathy and renal failure exacerbated by epsilon-aminocaproic
      acid.

PMID- 18805614
TI  - Effect of a vascular access nurse coordinator to reduce central venous catheter
      use in incident hemodialysis patients: a quality improvement report.
AB  - BACKGROUND: Starting hemodialysis therapy with an arteriovenous fistula (AVF) is
      associated with improved patient survival. Clinical audit showed that less than
      50% of our patients started hemodialysis therapy with an AVF. STUDY DESIGN:
      Quality improvement report, prospective before and after study. SETTING &
      PARTICIPANTS: Tertiary referral hospital with 184 patients starting hemodialysis
      therapy in 2005 and 2006. QUALITY IMPROVEMENT PLAN: Situational analysis showed
      poor overall coordination of surgical waiting lists. Multifaceted intervention
      included vascular access nurse coordinator and an algorithm to prioritize
      surgery. OUTCOMES: Vascular access used at first hemodialysis treatment in
      patients with pre-end-stage renal disease in the 12 months before and after the
      intervention. MEASUREMENTS: Proportions of patients starting hemodialysis therapy
      with an AVF. RESULTS: Overall, 65% of patients started hemodialysis therapy with
      an AVF; 2%, with an arteriovenous graft; and 33%, with a catheter. The proportion
      of patients starting hemodialysis therapy with an AVF increased from 56%
      preimplementation to 75% postimplementation (P = 0.007). After adjustment for
      age, sex, late referral, cause of renal failure, and presentation type, patients
      starting dialysis therapy in the implementation phase were twice as likely to
      start treatment with an AVF (odds ratio, 2.85; P = 0.008). The total number of
      catheter-days in the implementation phase was half that of the preimplementation
      phase (2,833 v 4,685 days). LIMITATIONS: Nonrandomized study. CONCLUSIONS:
      Implementation of a multifaceted intervention including a vascular access nurse
      and an algorithm to prioritize surgery significantly increased the proportion of
      patients starting dialysis therapy with an AVF by improving the overall
      coordination of the surgical waiting list.

PMID- 18805615
TI  - Public perception of and willingness to perform bystander CPR in Japan.
AB  - AIM: Immediate bystander cardiopulmonary resuscitation (CPR) is the most
      essential factor for life saving in out-of-hospital cardiac arrest patients. We
      investigated the characteristics associated with willingness to attempt CPR among
      the Japanese general population. METHODS: We randomly selected 2400 persons from
      all over Japan and conducted a questionnaire survey regarding their knowledge,
      experiences of and attitudes toward CPR. We performed descriptive statistics
      followed by multivariable logistic regression analyses. RESULTS: A total of 1132
      persons (47%) completed the questionnaire. Only 13% of the subjects were willing
      to attempt bystander CPR for their families and friends, and 7% were willing to
      attempt bystander CPR for strangers. Willingness to attempt CPR was independently
      associated with office workers or skilled workers [odds ratio (OR) 1.8; 95%
      confidence interval (CI): 1.1-2.7], having trained in CPR [OR: 3.1; 95% CI: 2.1
      4.6], actual experience with CPR [OR: 3.8; 95% CI: 1.7-8.3], and having friends
      with heart diseases [OR: 1.8; 95% CI: 1.05-3.0]. Having trained in CPR was
      independently associated with younger age [OR: 1.6; 95% CI: 1.2-2.1], office
      workers or skilled workers [OR: 1.5; 95% CI: 1.1-2.0], having driver's license
      [OR: 1.7; 95% CI: 1.2-2.4] and awareness of AED placement in a public space [OR:
      2.1; 95% CI: 1.4-3.1]. CONCLUSION: Experience of CPR training closely associated
      with willingness to attempt CPR, and awareness of AED in a public space are
      significant factors in CPR training. AED placement might call attention to CPR
      training and develops willingness to attempt CPR.

PMID- 18805616
TI  - Use of cold intravenous fluid to induce hypothermia in a comatose child after
      cardiac arrest due to a lightning strike.
AB  - We report a case in which mild hypothermia was induced successfully using a cold
      intravenous fluid infusion in a 12-year-old boy who was comatose following 21 min
      of cardiac arrest caused by a lightning strike.

PMID- 18805618
TI  - Towards an appropriate use of ultrasound in resuscitation.

PMID- 18805619
TI  - Use of therapeutic hypothermia in Polish intensive care units.

PMID- 18805620
TI  - Recommended guidelines for reporting on emergency medical dispatch when
      conducting research in emergency medicine: the Utstein style.
AB  - OBJECTIVES: To establish a uniform framework describing the system and
      organisation of emergency medical response centres and the process of emergency
      medical dispatching (EMD) when reporting results from studies in emergency
      medicine and prehospital care. DESIGN AND RESULTS: In September 2005 a task force
      of 22 experts from 12 countries met in Stavanger; Norway at the Utstein Abbey to
      review data and establish a common terminology for medical dispatch centres
      including core and optional data to be used for health monitoring, benchmarking
      and future research.

PMID- 18805621
TI  - Termination of resuscitation: a guide to interpreting the literature.
AB  - INTRODUCTION: Prehospital termination of resuscitation rules are used to decide
      on one of two actions: to continue resuscitation and transport to hospital or to
      terminate resuscitation. The literature is confusing as some rules are derived
      with survival as the outcome of interest (predicting when to transport and
      reporting sensitivity and negative predictive value) and other rules use death
      (predicting when to terminate resuscitation and reporting specificity and
      positive predictive value). Very few publish the EMS transport rate when the rule
      is applied; the outcome of interest to EMS services. METHODS: We propose to
      review the test characteristics and transport rates of the decision rules
      published between 1966 and 2007. RESULTS: We identified 9 analyses of 6
      termination of resuscitation rules; 1 inhospital, and 5 prehospital (2 advance
      and 3 basic life support providers). The inhospital and the basic life support
      rules were derived using survival whereas the advance life support rules were
      derived using death. The transport rate was published in two studies. When all
      the rules were reanalysed for death the specificity varied from 90.2% to 100%,
      the positive predictive value from 99.5% to 100% and the transport rate varied
      from 37% to 91%. CONCLUSION: We suggest that the diagnostic test characteristics
      of termination of resuscitation rules should be reported with death as the
      primary outcome which identifies for the paramedics futile resuscitations that
      should be terminated in the field. We also emphasize the need to report transport
      rates to provide the EMS services with an implementation benchmark.

PMID- 18805622
TI  - Caspase inhibitor zVAD.fmk reduces infarct size after myocardial ischaemia and
      reperfusion in rats but not in mice.
AB  - OBJECTIVE: Apoptosis of cardiomyocytes has been suggested to contribute to
      outcome following myocardial ischaemia and reperfusion (MI/R). Caspase inhibitors
      were developed as potential therapeutics for MI/R. However, various reports using
      the broad-spectrum caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp
      fluoromethylketone (zVAD.fmk) in the latter setting present conflicting results.
      Therefore, it is still unclear whether inhibition of apoptosis by caspase
      inhibitors promotes cardioprotection. MATERIALS AND METHODS: This study evaluated
      whether zVAD.fmk or novel caspase inhibitor quinoline-Val-Asp(Ome)-CH2-O-phenoxy
      (Q-VD-OPh) reduce myocardial infarct size in mice. Secondly, we tested zVAD.fmk's
      potential infarct-sparing effects in rats and whether these are accompanied by
      improved left ventricular function. RESULTS: In mice neither zVAD.fmk nor Q-VD
      OPh reduced infarct size. In rats, however, zVAD.fmk reduced infarct size
      following ischaemia (25min) and reperfusion (7 days) by approximately 53%. This
      was, however, accompanied by an increase in left ventricular end-diastolic
      pressure. CONCLUSION: This study provides further evidence that abrogation of
      apoptosis via caspase inhibition might not be sufficient to effectively limit
      infarct size following MI/R.

PMID- 18805623
TI  - Our battle with hexachlorobenzene: citizen perspectives on toxic waste in Botany.
AB  - The perspectives of residents are brought together in this assembly of statements
      concerning the management of hexachlorobenzene waste in Botany, a southeastern
      suburb of Sydney. The paper indicates how residents have responded as
      participants in public participation exercises, and the contribution made by lay
      experts in the search for a negotiated solution to the problems of legacy wastes.
      Resident comments on the role of independent scientific experts, on legal
      liability, and on the State Government sponsored Commission of Inquiry, indicate
      the deficit of resources faced by the local community. The paper provides
      insights into the status of citizen knowledge in environmental controversies and
      the pitfalls of participatory processes.

PMID- 18805624
TI  - Toxic waste in our midst: towards an interdisciplinary analysis.
AB  - Intractable industrial legacies present new challenges to governance. Amongst the
      persistent organic pollutants, now managed internationally under the Stockholm
      Convention, hexachlorobenzene (HCB) stands out in all three classes of chemicals
      (pesticides, industrial chemicals and unintended by-products). This paper
      introduces twelve interdisciplinary papers contributing to our understanding of
      decision-making processes using a case study of HCB and industry-community
      relations in Sydney's industrial heartland. In this collection, authors align new
      political theory and emerging management theory, and they analyse the case study
      from several disciplines. Disputes such as that over HCB destablilise the
      political/administrative/technoscientific regime that is the modern state.
      Citizens engage in 'sub-political' processes which require recognition of what
      Ulrich Beck and others have termed 'individualisation'. This sees decision
      forming and decision-making functions push outwards into community-driven
      structures. There we find new styles of public participation, resolution of
      asymmetries between knowledge and expertise, and new corporate behaviour.

PMID- 18805625
TI  - Toxic risk and governance: the case of hexachlorobenzene.

PMID- 18805626
TI  - In vivo monitoring of focused ultrasound surgery using local harmonic motion.
AB  - The present study established the feasibility of a technique for monitoring
      focused ultrasound (FUS) lesion formation in vivo using localized harmonic motion
      (LHM) measurements. Oscillatory motion (frequencies between 50 and 300 Hz) was
      generated within tissues by induction of a periodic radiation force with a FUS
      transducer. The harmonic motion was estimated using cross correlation of RF
      ultrasonic signals acquired at different instances during the motion by using a
      confocal diagnostic ultrasound transducer. The technique was evaluated in vivo in
      rabbit muscle (14 locations) in an magnetic resonance (MR) imager for
      simultaneous ultrasound harmonic motion tracking and MR thermometry. The measured
      maximum amplitude of the induced harmonic motion before and after the lesion
      formation was significantly different for all the tested motion frequencies, and
      decreased between 17 and 81% depending on the frequency and location. During the
      FUS exposure a drop in the maximum amplitude value was observed and a threshold
      value could be associated to the formation of a thermal lesion. A series of
      controlled sonications was performed by stopping the exposure when the threshold
      value in LHM amplitude was reached and the presence of a thermal lesion was
      confirmed by MR imaging. LHM measurements were also used to perform a spatial
      scan of the tissues across the exposure region and the thermal lesions could be
      detected as a reduction in the maximum motion amplitude value at the sonication
      region.

PMID- 18805627
TI  - Renal vascular perfusion index in a canine model.
AB  - Decreased renal perfusion plays an important role in the progression toward renal
      failure. In this study, a novel measure was proposed to quantify renal perfusion
      using canine model. Serial renal vascular images at different vascular areas
      including the whole vascular tree, interlobar, arcuate and interlobular vessels
      were captured. Image processing software was designed to analyze the changes of
      power Doppler intensity of colored pixels within regions-of-interest (ROI). For a
      given ROI, the power Doppler vascular index (PDVI) was found to fluctuate with
      the cardiac cycle. It was also noted that the power Doppler signals generated by
      arterial vessels have different fluctuating waveforms and different phase
      compared with the signal derived from venous vessels. A power Doppler correlation
      map was developed to differentiate the arteries and veins in the ROI. Using the
      serial power Doppler images and the derived flow direction information, the
      interlobular perfusion can be strongly quantified. The renal vascular perfusion
      index (RVPI) defined as the ratio of PDVI(max) versus PDVI(min) was significantly
      higher in the interlobular vessel areas than three other areas for seven healthy
      dogs. The RVPI resembles the systolic/diastolic (S/D) ratio that commonly
      reflects arterial hemodynamics. RVPI and power Doppler correlation-map reveal
      more "dynamic" sense of vascular perfusion and provide a novel approach for the
      examination of renal function in clinical practice.

PMID- 18805628
TI  - Outcomes of men with screen-detected prostate cancer eligible for active
      surveillance who were managed expectantly.
AB  - BACKGROUND: The incidence of small, localised, well-differentiated prostate
      cancer (PCa) is increasing, mainly as a result of screening. Many of these
      cancers will not progress, and radical therapy may lead to substantial
      overtreatment. Active surveillance (AS) has emerged as an alternative. OBJECTIVE:
      To retrospectively validate the currently used criteria for eligibility for AS.
      DESIGN, SETTING, AND PARTICIPANTS: For this cohort study, data from 616 men who
      were diagnosed with PCa between 1994 and 2007 at a mean age of 66.3 yr in four
      centres of the European Randomized Study of Screening for Prostate Cancer (ERSPC)
      were combined. All patients fit the criteria for AS (prostate-specific antigen
      [PSA] < or = 10.0 ng/ml, PSA-density < 0.2 ng/ml per ml, stage T1C/T2, Gleason
      score < or = 3 + 3 = 6, and < or = 2 positive biopsy cores), and initially they
      were managed expectantly. Median follow-up was 3.91 yr. MEASUREMENTS: Disease
      specific-, overall-, and treatment-free survival were studied. Present PSA
      characteristics were assessed and also compared between men who were switching to
      deferred active therapy during follow-up and men remaining untreated. RESULTS AND
      LIMITATIONS: The calculated (Kaplan-Meier) 10-yr PCa-specific survival (21
      patients at risk) was 100%, which sharply contrasted with 77% overall survival.
      Men still alive showed favourable PSA characteristics. Although the calculated 10
      yr treatment-free survival was only 43%, objective signs of progression often did
      not indicate the shift to radical treatment. The cohort consisted of men on AS
      and those on watchful waiting (WW); information on comorbidity or psychological
      distress was not available. CONCLUSIONS: AS seems justified in selected men with
      screen-detected PCa. Prospective protocol-based AS programs are necessary to
      optimise selection criteria and to find the appropriate trigger points for
      switching to active therapy. Possible negative psychological reactions with AS
      against improved quality of life by withholding side-effects from radical
      treatment should be considered.

PMID- 18805629
TI  - Laparoscopic dismembered pyeloplasty of a retrocaval ureter: case report and
      review of the literature.
AB  - A retrocaval ureter is a rare entity that has traditionally been treated with
      open pyeloplasty techniques. In this paper, we describe the successful
      performance of a laparoscopic dismembered pyeloplasty for a retrocaval ureter and
      present important technical points. In reviewing the available literature about
      this technique, the laparoscopic approach should be considered to be first-line
      treatment for this anatomic anomaly due to the good track record, quick
      convalescence, and relative technical ease.

PMID- 18805630
TI  - Botulinum neurotoxin type A: the poison that can treat the sick.

PMID- 18805631
TI  - Serum polyamines in pre- and post-operative patients with breast cancer corrected
      by menopausal status.
AB  - Polyamines are essential for cell growth and differentiation of cells and its
      increased production is observed in many cancers. Due to one of key enzymes in
      polyamine synthesis ornithine decarboxylase is stimulated by estrogens in breast
      cancer cells, the polyamine levels in serum samples obtained from patients with
      breast cancer (BCa; pre-menopause: 45.6+/-0.8 years old, n=58; post-menopause:
      55.2+/-1.1 years old; n=11), who were also classified as pre- and post-surgery,
      and from normal controls (pre-menopause: ages 43.6+/-0.9 years, n=45, post
      menopause: ages 55.2+/-1.0 years, n=18) were determined by liquid chromatography
      mass spectrometry. In pre-menopausal patients, the concentrations of 1,3
      diaminopropane, N-acetyl putrescine (N-actPut), N-acetyl spermidine and
      spermidine (Sp) were higher (p<0.05) in pre-surgery breast cancer patients than
      in normal controls, with N-actPut (p<0.0005) and Sp (p<0.005) levels markedly
      increased. All polyamine levels were slightly decreased post-surgery, and were
      comparable to levels in normal subjects. Based on menopausal-dependent data, the
      results imply that serum polyamines levels may correlate with estrogen levels in
      association with estrogen-induced cell growth and ornithine decarboxylase
      activity.

PMID- 18805632
TI  - Nitric oxide-donating aspirin inhibits the growth of pancreatic cancer cells
      through redox-dependent signaling.
AB  - The novel chemopreventive nitric oxide-donating aspirin (NO-ASA) prevents nearly
      90% of ductal adenocarcinomas in a animal tumor model. To decipher the mechanism
      of this effect, we studied in BxPC-3 human pancreatic cancer cells the sequence
      of signaling events leading from NO-ASA treatment to cell growth inhibition. NO
      ASA inhibited the growth of BxPC-3 cells (IC(50) =13 microM), by inhibiting
      proliferation modestly and inducing apoptosis, necrosis and G(1)/S cell cycle
      block. At 15 min of treatment with NO-ASA, the intracellular levels of reactive
      oxygen species (ROS) began increasing (peak at 8h, baseline levels by 24h). ROS
      activated almost immediately in a time- and concentration-dependent manner the
      MAPK pathways p38, ERK and JNK (their activation was abrogated by the antioxidant
      N-acetylcysteine). MAPK activation induced p21(cip-1), which suppressed the
      levels of cyclin D1 that controls the G(1)/S cell cycle transition. NO-ASA
      induced COX-2 expression starting 90 min after p21(cip-1) was induced. When COX-2
      expression was knocked down using siRNA against cox-2, the expression of p21(cip
      1) was induced by NO-ASA, regardless of the level of expression of COX-2,
      suggesting a marginal, if any, role for COX-2 in the growth inhibitory effect of
      NO-ASA. These findings along with the temporal sequence of individual changes
      indicate a signaling sequence that involves ROS-->MAPKs-->p21(cip-1)-->cyclin D1-
      >cell death. Our findings establish the critical role of ROS as proximal
      signaling molecules in the action of anticancer compounds and may be useful in
      designing mechanism-driven approaches to cancer control.

PMID- 18805633
TI  - The N-terminal domain of EBNA1 acts as a suppressor of the HER2/neu oncogene.
AB  - HER2/neu oncogene-mediated malignancy is clearly associated with various human
      cancers. Therefore, HER2/neu targeting is an effective approach to cancer
      therapy. We have previously demonstrated that Epstein-Barr virus nuclear antigen
      1 (EBNA1) can suppress HER2/neu oncogene expression, although EBNA1 itself has
      oncogenic potential. Here, we found that the N-terminal domain of EBNA1 alone,
      named EBNA1-NT, which contains the N-terminal region of amino acid residues 1-86
      of EBNA1, is required and sufficient to suppress HER2/neu oncogene expression at
      the transcriptional level. Furthermore, in EBNA1-NT-transfected HER2/neu
      overexpressing cells, we found EBNA1-NT could down-regulate the endogenous
      production of p185(HER2/neu), lower transformation ability, sensitize paclitaxel
      induced apoptosis and decrease tumorigenic potential. These data suggest that
      EBNA1-NT may act as a repressor of the HER2/neu oncogene.

PMID- 18805634
TI  - Expression of DNA damage response genes indicate progressive breast tumors.
AB  - To assess how the abnormal expression of DNA damage response (DDR) genes
      correlate with oncogenesis, we analyzed mRNA levels of ATM-CHK2-P53 axis in 65
      sporadic breast tumors by real-time PCR followed by evaluation of P53 protein and
      its activation status in representative samples. Univariate analysis showed a
      significantly higher transcript level for ATM (P=0.002), MDM2 (P=0.015) and p21
      (P=0.013) in stage 1 tumors when compared against those of later stages. Although
      p53 transcript levels showed the characteristic increase in stage 1, a fourfold
      increase of p53 in N3 tumors than other nodal stages (P=0.0007) significantly
      increased its expression in stage 3B. The accumulated p53 at stage 3B, confirmed
      also at the protein level (P=0.012), was rendered nonfunctional by reduced P53
      activation (p-P53Ser15; P=0.00007) or increased rate of mutation, substantiated
      further by the corresponding failure of upregulation of downstream genes, MDM2
      and p21. We conclude that the alteration of DDR expression facilitates tumor
      progression and its possible therapeutic implications need to be studied in
      future.

PMID- 18805635
TI  - Photo degradation of methyl orange an azo dye by advanced Fenton process using
      zero valent metallic iron: influence of various reaction parameters and its
      degradation mechanism.
AB  - Advanced Fenton process (AFP) using zero valent metallic iron (ZVMI) is studied
      as a potential technique to degrade the azo dye in the aqueous medium. The
      influence of various reaction parameters like effect of iron dosage,
      concentration of H(2)O(2)/ammonium per sulfate (APS), initial dye concentration,
      effect of pH and the influence of radical scavenger are studied and optimum
      conditions are reported. The degradation rate decreased at higher iron dosages
      and also at higher oxidant concentrations due to the surface precipitation which
      deactivates the iron surface. The rate constant for the processes Fe(0)/UV and
      Fe(0)/APS/UV is twice compared to their respective Fe(0)/dark and Fe(0)/APS/dark
      processes. The rate constant for Fe(0)/H(2)O(2)/UV process is four times higher
      than Fe(0)/H(2)O(2)/dark process. The increase in the efficiency of Fe(0)/UV
      process is attributed to the cleavage of stable iron complexes which produces
      Fe(2+) ions that participates in cyclic Fenton mechanism for the generation of
      hydroxyl radicals. The increase in the efficiency of Fe(0)/APS/UV or H(2)O(2)
      compared to dark process is due to continuous generation of hydroxyl radicals and
      also due to the frequent photo reduction of Fe(3+) ions to Fe(2+) ions. Though
      H(2)O(2) is a better oxidant than APS in all respects, but it is more susceptible
      to deactivation by hydroxyl radical scavengers. The decrease in the rate constant
      in the presence of hydroxyl radical scavenger is more for H(2)O(2) than APS. Iron
      powder retains its recycling efficiency better in the presence of H(2)O(2) than
      APS. The decrease in the degradation rate in the presence of APS as an oxidant is
      due to the fact that generation of free radicals on iron surface is slower
      compared to H(2)O(2). Also, the excess acidity provided by APS retards the
      degradation rate as excess H(+) ions acts as hydroxyl radical scavenger. The
      degradation of Methyl Orange (MO) using Fe(0) is an acid driven process shows
      higher efficiency at pH 3. The efficiency of various processes for the de
      colorization of MO dye is of the following order:
      Fe(0)/H(2)O(2)/UV>Fe(0)/H(2)O(2)/dark>Fe(0)/APS/UV>Fe(0)/UV>Fe(0)/APS/dark>H(2)O(
      )/UV approximately Fe(0)/dark>APS/UV. Dye resisted to degradation in the presence
      of oxidizing agent in dark. The degradation process was followed by UV-vis and GC
      MS spectroscopic techniques. Based on the intermediates obtained probable
      degradation mechanism has been proposed. The result suggests that complete
      degradation of the dye was achieved in the presence of oxidizing agent when the
      system was amended with iron powder under UV light illumination. The
      concentration of Fe(2+) ions leached at the end of the optimized degradation
      experiment is found to be 2.78 x 10(-3)M. With optimization, the degradation
      using Fe(0) can be effective way to treat azo dyes in aqueous solution.

PMID- 18805636
TI  - The simulation of air recirculation and fire/explosion phenomena within a
      semiconductor factory.
AB  - The semiconductor industry is the collection of capital-intensive firms that
      employ a variety of hazardous chemicals and engage in the design and fabrication
      of semiconductor devices. Owing to its processing characteristics, the fully
      confined structure of the fabrication area (fab) and the vertical airflow
      ventilation design restrict the applications of traditional consequence analysis
      techniques that are commonly used in other industries. The adverse situation also
      limits the advancement of a fire/explosion prevention design for the industry. In
      this research, a realistic model of a semiconductor factory with a fab, sub
      fabrication area, supply air plenum, and return air plenum structures was
      constructed and the computational fluid dynamics algorithm was employed to
      simulate the possible fire/explosion range and its severity. The semiconductor
      factory has fan module units with high efficiency particulate air filters that
      can keep the airflow uniform within the cleanroom. This condition was modeled by
      25 fans, three layers of porous ceiling, and one layer of porous floor. The
      obtained results predicted very well the real airflow pattern in the
      semiconductor factory. Different released gases, leak locations, and leak rates
      were applied to investigate their influence on the hazard range and severity.
      Common mitigation measures such as a water spray system and a pressure relief
      panel were also provided to study their potential effectiveness to relieve
      thermal radiation and overpressure hazards within a fab. The semiconductor
      industry can use this simulation procedure as a reference on how to implement a
      consequence analysis for a flammable gas release accident within an air
      recirculation cleanroom.

PMID- 18805637
TI  - Effect of pre-treatments on hydrolysis and methane production potentials of by
      products from meat-processing industry.
AB  - In this study, the effect of five pre-treatments (thermal, ultrasound, acid, base
      and bacterial product) on hydrolysis and methane production potentials of four by
      products from meat-processing industry was studied. The bacterial product Liquid
      Certizyme 5 increased soluble chemical oxygen demand (CODsol) of digestive tract
      content and drumsieve waste the most as compared to untreated material (62 and
      96%, respectively), while ultrasound was the most effective to increase CODsol
      with dissolved air flotation (DAF) sludge (88%) and grease trap sludge (188%). In
      batch experiments, thermal treatment increased methane production potential of
      drumsieve waste, acid of grease trap sludge and all pre-treatments of DAF sludge.
      However, with all other pre-treatments, methane production potential was
      decreased compared to untreated materials, apparently due to inhibition by
      hydrolysis products and/or possible re-crystallization of some compounds. Methane
      production potentials from the untreated materials were as follows: digestive
      tract content 400+/-50m(3)CH(4)/t volatile solids (VS)(added), drumsieve waste
      230+/-20m(3)CH(4)/tVS(added), DAF sludge 340+/-17m(3)CH(4)/tVS(added) and grease
      trap sludge 900+/-44m(3)CH(4)/tVS(added).

PMID- 18805638
TI  - Coal fly ash and synthetic coal fly ash aggregates as reactive media to remove
      zinc from aqueous solutions.
AB  - Coal fly ash (CF) and synthetic coal fly ash aggregates (SCFAs) were evaluated as
      low-cost reactive media for the remediation of groundwater contaminated with Zn.
      The SCFAs were prepared by mixing CF, sodium silicate, and deionized (DI) water.
      Serial batch kinetic and static tests were conducted on both CF and SCFAs, under
      various conditions (i.e., pH, initial Zn concentration, reaction time, and solid
      dosage), using Zn(NO(3))(2).6H(2)O solutions. Serial column tests were also
      conducted on both CF and SCFAs. The final rather than the initial pH of the
      solution had a greater effect on the removal of Zn. At pH>7.0, the removal of Zn
      was due to precipitation, whereas at <7.0, the removal of Zn was due to
      adsorption onto the reactive media. The removal of Zn increased with increasing
      dosage of the reactive medium and decreasing initial Zn concentration. The
      results of the column and batch tests were comparable. Preferential flow paths
      were observed with CF, but not SCFA. The hydraulic conductivity of CF was more
      significantly decreased than that of SCFA with increasing dry density of the
      specimen.

PMID- 18805639
TI  - Estimation of toxicity of ionic liquids in Leukemia Rat Cell Line and
      Acetylcholinesterase enzyme by principal component analysis, neural networks and
      multiple lineal regressions.
AB  - Multiple linear regression (MLR), radial basis network (RB), and multilayer
      perceptron (MLP) neural network (NN) models have been explored for the estimation
      of toxicity of ammonium, imidazolium, morpholinium, phosphonium, piperidinium,
      pyridinium, pyrrolidinium and quinolinium ionic liquid salts in the Leukemia Rat
      Cell Line (IPC-81) and Acetylcholinesterase (AChE) using only their empirical
      formulas (elemental composition) and molecular weights. The toxicity values were
      estimated by means of decadic logarithms of the half maximal effective
      concentration (EC(50)) in microM (log(10)EC(50)). The model's performances were
      analyzed by statistical parameters, analysis of residuals and central tendency
      and statistical dispersion tests. The MLP model estimates the log(10)EC(50) in
      IPC-81 and AchE with a mean prediction error less than 2.2 and 3.8%,
      respectively.

PMID- 18805640
TI  - Nitrate removal from electro-oxidized landfill leachate by ion exchange.
AB  - Treatment of landfill leachates by electrochemical oxidation led to the complete
      removal of chemical oxygen demand and ammonium nitrogen. However, as result of
      the ammonium oxidation, the partial formation of nitrate ions was observed. Ion
      exchange technology was investigated as a polishing step in the treatment of
      landfill leachates. Removal of nitrate from aqueous solutions was studied using
      two selective anion exchangers: Purolite A 520E and Purolite A 300, under a fixed
      bed configuration. The following aspects of the ion exchange system were
      experimentally analyzed: (i) the influence of the presence of other competitive
      anions in solution, sulfate and chloride, during the loading step, (ii) the
      breakthrough point and resin saturation as a function of chloride concentration
      in the feed stream and, (iii) the efficiency of the regeneration step working
      with NaCl solutions at several concentrations. After a comparison of the
      experimental results, it was concluded that the resin Purolite A 300 showed a
      better behavior. Experimental analysis of the equilibrium isotherms made it
      possible to determine the equilibrium constant (K=3.21) and the maximum capacity
      (q(max)=183mgg(-1)), important parameters in the design of the treatment process.

PMID- 18805641
TI  - HPA axis hyperactivity as suicide predictor in elderly mood disorder inpatients.
AB  - Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis function is
      associated with suicidal behaviour and age-associated alterations in HPA axis
      functioning may render elderly individuals more susceptible to HPA dysregulation
      related to mood disorders. Research on HPA axis function in suicide prediction in
      elderly mood disorder patients is sparse. The study sample consisted of 99
      depressed elderly inpatients 65 years of age or older admitted to the department
      of Psychiatry at the Karolinska University Hospital between 1980 and 2000. The
      hypothesis was that elderly mood disorder inpatients who fail to suppress
      cortisol in the dexamethasone suppression test (DST) are at higher risk of
      suicide. The DST non-suppression distinguished between suicides and survivors in
      elderly depressed inpatients and the suicide attempt at the index episode was a
      strong predictor for suicide. Additionally, the DST non-suppression showed higher
      specificity and predictive value in the suicide attempter group. Due to age
      associated alterations in HPA axis functioning, the optimal cut-off for DST non
      suppression in suicide prediction may be higher in elderly mood disorder
      inpatients. These data demonstrate the importance of attempted suicide and DST
      non-suppression as predictors of suicide risk in late-life depression and suggest
      the use for neuroendocrine testing of HPA axis functioning as a complementary
      tool in suicide prevention.

PMID- 18805642
TI  - The ratio of cortisol/DHEA in treatment resistant depression.
AB  - OBJECTIVE: Hypercortisolaemia has been well described in depression and may be a
      factor associated with treatment resistance. The role of the more abundant
      adrenal steroid dehydroepiandrosterone (DHEA) has been recently investigated,
      with some evidence that it may have an antiglucocorticoid effect. This study
      measured cortisol, DHEA and their ratio in treatment resistant depression (TRD)
      and healthy controls and also related these measures to treatment outcome.
      METHOD: Plasma cortisol, DHEA and cortisol/DHEA ratio were determined at 0900h in
      28 patients with TRD and 40 healthy controls. The measures were repeated
      following inpatient treatment in a subgroup of 21 patients and related to the
      outcome of such treatment. The stability of cortisol/DHEA ratios was assessed
      with 2 hourly samples from 0900 to 1700h in a subgroup of 15 controls. RESULTS:
      Basal levels of cortisol and the cortisol/DHEA ratio were higher in patients
      compared to controls. Whilst cortisol levels were lower after treatment, there
      was no relationship between cortisol levels and treatment outcome. In contrast,
      treatment responders had significantly lower DHEA on admission and a higher
      cortisol/DHEA ratio both on admission and on discharge. Cortisol/DHEA ratios were
      stable between 9 a.m. and 5 p.m. CONCLUSIONS: In addition to cortisol, the
      cortisol/DHEA ratio is raised in TRD; thus, there is no evidence that DHEA levels
      could negate the increased glucocorticoid activity in TRD. Patients with a more
      abnormal cortisol/DHEA ratio, possibly indicating greater biological dysfunction,
      responded preferentially to inpatient therapy, though the raised cortisol/DHEA
      ratio persisted after response. The cortisol/DHEA ratio is stable throughout the
      day and may be a more practical biological marker of TRD.

PMID- 18805643
TI  - Architectural changes to CA1 pyramidal neurons in adult and aged mice after
      peripheral immune stimulation.
AB  - The expression of several inflammatory cytokines that inhibit synaptic plasticity
      and hippocampal-dependent learning and memory is higher in the brains of aged
      mice compared to young adults after peripheral injection of lipopolysaccharide
      (LPS). In this study we investigated whether the exaggerated inflammatory
      cytokine response in the hippocampus of aged mice after IP injection of LPS is
      associated with architectural changes to dendrites of pyramidal neurons in the
      dorsal CA1 hippocampus. Compared to young adults, aged mice had higher basal
      expression of MHC class II, lower basal expression of two neurotrophins, nerve
      growth factor (NGF) and brain-derived neurotrophic factor (BDNF), and a decrease
      in total dendritic length in both the basal and apical tree. After IP LPS
      administration, expression of IL-1beta, IL-6, and TNFalpha mRNA was higher in
      hippocampus of aged mice compared to young adults whereas NGF and BDNF mRNA was
      reduced similarly in both age groups. The basal dendritic tree was not affected
      by LPS in either adult or aged mice 72h after treatment; however, length and
      branching of the apical tree was reduced by LPS in aged but not adult mice. The
      present findings indicate that a peripheral infection in the aged can cause a
      heightened inflammatory cytokine response in the hippocampus and atrophy of
      hippocampal neurons. Architectural changes to dorsal CA1 hippocampal neurons may
      contribute to cognitive disorders evident in elderly patients with an infection.

PMID- 18805644
TI  - Circadian genes: mystery underlying the physiopathology of infantile colic.

PMID- 18805645
TI  - Can transcendental meditation exercise a miraculous control over long-standing
      epilepsy?

PMID- 18805646
TI  - Endogenous hallucinogens as ligands of the trace amine receptors: a possible role
      in sensory perception.
AB  - While the endogenous hallucinogens, N,N-dimethyltryptamine, 5-hydroxy-N,N
      dimethyl-tryptamine and 5-methoxy-N,N-dimethyltryptamine, have been acknowledged
      as naturally occurring components of the mammalian body for decades, their
      biological function remains as elusive now as it was at the time of their
      discovery. The recent discovery of the trace amine associated receptors and the
      activity of DMT and other hallucinogenic compounds at these receptor sites leads
      to the hypothesis that the endogenous hallucinogens act as neurotransmitters of a
      subclass of these trace amine receptors. Additionally, while activity at the
      serotonin 5-HT2A receptor has been proposed as being responsible for the
      hallucinogenic affects of administered hallucinogens, in their natural setting
      the 5-HT2A receptor may not interact with the endogenous hallucinogens at all.
      Additionally 5-HT2A agonist activity is unable to account for the visual altering
      effects of many of the administered hallucinogens; these effects may be mediated
      by one of the endogenous hallucinogen trace amine receptors rather than the
      serotonin 5-HT2A receptor. Therefore, activity at the trace amine receptors, in
      addition to serotonin receptors, may play a large role in the sensory altering
      effects of administered hallucinogens and the trace amine receptors along with
      their endogenous hallucinogen ligands may serve an endogenous role in mediating
      sensory perception in the mammalian central nervous system. Thus the theory
      proposed states that these compounds act as true endogenous hallucinogenic
      transmitters acting in regions of the central nervous system involved in sensory
      perception.

PMID- 18805647
TI  - Lipoid pneumonia with chronic myelomonocytic leukemia.
AB  - A case of lipoid pneumonia with chronic myelomonocytic leukemia is reported. A 61
      year-old man was autopsied after suffering from myelodysplastic syndrome (chronic
      myelomonocytic leukemia) for 13 years. Interstitial lesions of the lungs were
      suspected as infiltration of leukemia cells before the autopsy. However, blastic
      leukemia cells were not observed in the lung, although they were seen in the bone
      marrow and spleen at autopsy. Instead, an unusual amount of cholesterol deposits
      was observed with mucormycosis and aspergillosis in the lungs. Cholesterol
      deposition was observed not only in perihilar but also in subpleural regions
      without apparent bronchial obstruction in both lungs. It is thought that
      malfunction of monocytes/macrophages resulted in repeated fungal infection and
      storage of cholesterol caused by tissue destruction and impaired tissue
      repairing.

PMID- 18805648
TI  - DNA double-strand break rejoining in complex normal tissues.
AB  - PURPOSE: The clinical radiation responses of different organs vary widely and
      likely depend on the intrinsic radiosensitivities of their different cell
      populations. Double-strand breaks (DSBs) are the most deleterious form of DNA
      damage induced by ionizing radiation, and the cells' capacity to rejoin radiation
      induced DSBs is known to affect their intrinsic radiosensitivity. To date, only
      little is known about the induction and processing of radiation-induced DSBs in
      complex normal tissues. Using an in vivo model with repair-proficient mice, the
      highly sensitive gammaH2AX immunofluorescence was established to investigate
      whether differences in DSB rejoining could account for the substantial
      differences in clinical radiosensitivity observed among normal tissues. METHODS
      AND MATERIALS: After whole body irradiation of C57BL/6 mice (0.1, 0.5, 1.0, and
      2.0 Gy), the formation and rejoining of DSBs was analyzed by enumerating
      gammaH2AX foci in various organs representative of both early-responding (small
      intestine) and late-responding (lung, brain, heart, kidney) tissues. RESULTS: The
      linear dose correlation observed in all analyzed tissues indicated that gammaH2AX
      immunofluorescence allows for the accurate quantification of DSBs in complex
      organs. Strikingly, the various normal tissues exhibited identical kinetics for
      gammaH2AX foci loss, despite their clearly different clinical radiation
      responses. CONCLUSION: The identical kinetics of DSB rejoining measured in
      different organs suggest that tissue-specific differences in radiation responses
      are independent of DSB rejoining. This finding emphasizes the fundamental role of
      DSB repair in maintaining genomic integrity, thereby contributing to cellular
      viability and functionality and, thus, tissue homeostasis.

PMID- 18805649
TI  - Comparison of toxicity associated with early morning versus late afternoon
      radiotherapy in patients with head-and-neck cancer: a prospective randomized
      trial of the National Cancer Institute of Canada Clinical Trials Group (HN3).
AB  - PURPOSE: Based on our demonstration of a circadian rhythm in the human oral
      mucosa cell cycle, with most cells in the G(1) phase in the morning and M phase
      at night, we hypothesized that morning radiotherapy (RT) would lead to less oral
      mucositis than afternoon RT. METHODS AND MATERIALS: A total of 216 patients were
      randomized to morning (8-10 AM) vs. afternoon (4-6 PM) RT and stratified by
      radiation dose, smoking status, and center. Patients receiving primary or
      postoperative RT alone were eligible. Oral mucositis was scored using the
      Radiation Therapy Oncology Group (RTOG) criteria and a validated scoring system.
      RESULTS: Of 205 evaluable patients, 52.9% vs. 62.4% developed RTOG Grade 3 or
      greater mucositis after morning vs. afternoon RT, respectively (p = 0.17).
      Morning RT was also associated with significantly less weight loss after 5 months
      (p = 0.024). In a subgroup of 111 patients treated to a dose of 66-70 Gy in 33-35
      fractions, exploratory analyses revealed a significant reduction in Grade 3 or
      greater mucositis with morning RT (44.6% vs. 67.3%, p = 0.022) and a longer
      interval to the development of Grade 3 or greater mucositis (median, >7.9 vs. 5.6
      weeks, p = 0.033). In 53 patients, who smoked during therapy, a significant
      reduction was found in Grade 3 or greater mucositis with morning RT (42.9% vs.
      76%, p = 0.025). CONCLUSION: In this proof of principle study, morning RT was
      associated with significantly less weight loss after 5 months and an apparent
      reduction in oral mucositis in a subset of patients receiving >/=66 Gy and in
      patients who smoked during therapy.

PMID- 18805650
TI  - Breast cancer regional radiation fields for supraclavicular and axillary lymph
      node treatment: is a posterior axillary boost field technique optimal?
AB  - PURPOSE: To assess whether using an anterior oblique supraclavicular (SCV) field
      with a posterior axillary boost (PAB) field is an optimal technique for targeting
      axillary (AX) lymph nodes compared with two computed tomography (CT)-based
      techniques: (1) an SCV field with an anterior boost field and (2) intensity
      modulated radiotherapy (IMRT). METHODS AND MATERIALS: Ten patients with CT
      simulation data treated with postmastectomy radiation that included an SCV field
      were selected for the study. Supraclavicular nodes and AX Level I-III nodes
      within the SCV field were contoured and defined as the treatment target. Plans
      using the three techniques were generated and evaluated for each patient.
      RESULTS: The anterior axillary boost field and IMRT resulted in superior dose
      coverage compared with PAB. Namely, treatment volumes that received 105%, 80%,
      and 30% of prescribed dose for IMRT plans were significantly less than those for
      the anterior axillary boost plans, which were significantly less than PAB. For
      PAB and anterior axillary boost plans, there was a linear correlation between
      treatment volume receiving 105% of prescribed dose and maximum target depth.
      Furthermore, the IMRT technique resulted in better lung sparing and dose
      conformity to the target than anterior axillary boost, which again was
      significantly better than PAB. The maximum cord dose for IMRT was small, but
      higher than for the other two techniques. More monitor units were required to
      deliver the IMRT plan than the PAB plan, which was more than the anterior
      axillary boost plan. CONCLUSIONS: The PAB technique is not optimal for treatment
      of AX lymph nodes in an SCV field. We conclude that CT treatment planning with
      dose optimization around delineated target volumes should become standard for
      radiation treatments of supraclavicular and AX lymph nodes.

PMID- 18805651
TI  - Concurrent chemoradiotherapy in resected extrahepatic cholangiocarcinoma.
AB  - PURPOSE: Extrahepatic cholangiocarcinoma is a rare malignancy. Despite radical
      resection, survival remains poor, with high rates of local and distant failure.
      To clarify the role of radiotherapy with chemotherapy, we performed a
      retrospective analysis of resected patients who had undergone chemoradiotherapy.
      METHODS AND MATERIALS: A total of 45 patients (13 with proximal and 32 with
      distal disease) underwent resection plus radiotherapy (median dose, 50.4 Gy). All
      but 1 patient received concurrent fluoropyrimidine-based chemotherapy. The median
      follow-up was 30 months for all patients and 40 months for survivors. RESULTS: Of
      the 45 patients, 33 underwent adjuvant radiotherapy, and 12 were treated
      neoadjuvantly. The 5-year actuarial overall survival, disease-free survival,
      metastasis-free survival, and locoregional control rates were 33%, 37%, 42%, and
      78%, respectively. The median survival was 34 months. No patient died
      perioperatively. Patient age </=60 years and perineural involvement adversely
      affected survival on univariate analysis. Patients undergoing R0 resection had a
      significantly improved rate of local control but no survival advantage. Despite
      having more advanced disease at presentation, patients treated neoadjuvantly had
      a longer survival (5-year survival 53% vs. 23%, p = 0.16) and similar rates of
      Grade 2-3 surgical morbidity (16% vs. 33%, p = 0.24) compared with those treated
      in the postoperative setting. CONCLUSION: These study results suggest a possible
      local control benefit from chemoradiotherapy combined with surgery in patients
      with advanced, resected biliary cancer. Furthermore, our results suggest that a
      treatment strategy that includes preoperative chemoradiotherapy might result in
      improved tumor resectability with similar surgical morbidity compared with
      patients treated postoperatively, as well as potentially improved survival
      outcomes. Distant failure remains a significant failure pattern, suggesting the
      need for more effective systemic therapy.

PMID- 18805652
TI  - Genetic variation in Transaldolase 1 and risk of squamous cell carcinoma of the
      head and neck.
AB  - BACKGROUND: The Pentose Phosphate Pathway (PPP) is involved in the body's
      protection against oxidative stress and resistance/susceptibility to apoptosis
      and thus has been implicated in tumor development and progression. Here we
      present data examining the association of genetic variation in one of the key
      enzymes of the PPP, Transaldolase 1 (TALDO1) with squamous cell carcinoma of the
      head and neck (SCCHN). METHODS: We performed sequencing analysis to identify
      common genetic variations in TALDO1 and then investigated their association with
      SCCHN using samples from a population-based case/control study with both European
      American (EA) and African American (AA) former and current smokers. RESULTS: We
      identified three polymorphisms in TALDO1 that were associated with SCCHN risk in
      our EA study population. Specifically the 5' upstream variant -490C>G or T
      (rs10794338), which we identified as tri-allelic, showed a reduced risk compared
      with any presence of the common allele, odds ratio (OR) [95% confidence interval
      (95% CI)]: 0.57 (0.38-0.86). Additionally two intronic high frequency
      polymorphisms demonstrated a positive association with disease, with the presence
      of the variant IVS1+1874T>A (rs3901233), 1.76 (1.19-2.61) and IVS4+2187A>C
      (rs4963163), 1.71 (1.16-2.53). CONCLUSION: These results provide preliminary
      evidence that genetic polymorphisms in TALDO1 are associated with SCCHN.

PMID- 18805653
TI  - [Length of pushing efforts: pushing is not playing. Reply to the article of C. Le
      Ray and F. Audibert].
AB  - The aim of this work is to answer constructively to C. Le Ray and F. Audibert who
      were surprised that the French guidelines recommended an assisted delivery after
      30 min pushing, even if the fetal heart rate is reassuring. We first resumed the
      definition of "second stage of labor", this word including the first phase with
      no pushing efforts and the second phase with active pushing of the mother. With
      that definition, the length of the second stage is around 60 min for the
      primipara and 20 min for the multipara, this length being modified by the use of
      peridural. We then specified the physiological mechanisms influencing the
      acidobasic equilibrium during the pushing time. Those mechanisms are difficult to
      consider because foetal heart rate monitoring is often "lost" during that phase.
      Altogether, these factors bring incertitude about progressive foetal acidosis and
      incapacity to diagnose it. Finally, the literature analysis teaches us that
      increasing the second stage of labor (inactive plus active phases) during the
      normal pregnancy seems to be at low risk for the foetus within the primiparas,
      but display a risk for the mother and so might be limited. Comparing the delayed
      pushing with the immediate pushing only lead us to conclude that delayed pushing
      is dangerous, as is prolonged second stage. In conclusion, we think that
      prolonging the second stage of labor is possible but must be by increasing the
      inactive first phase of the second stage, especially as long as we will not get a
      noninvasive and reliable method allowing assessing the well-being of the foetus.

PMID- 18805654
TI  - [Giant leiomyoma of fallopian tube: a rare aetiology of abdominal tumor].
AB  - Leiomyomas of the fallopian tube are extremely rare. They are often managed with
      autopsy or surgery. We report a revealed case by a voluminous-abdominal mass in a
      35-year-old woman. Neither the tomodensitometry nor, even, the laparoscopy did
      not permit specifying the tubal origin of the tumor. The diagnosis has been
      finally carried to the laparotomy. An annexectomy had been achieved. The
      histological examination concluded to a leiomyoma without malignant-cellular
      atypia.

PMID- 18805655
TI  - Incidence and determinants of initiation into cocaine injection and correlates of
      frequent cocaine injectors.
AB  - PURPOSE: To investigate the incidence and correlates of cocaine injection
      initiation and the impacts of daily cocaine injection among a cohort of injection
      drug users. METHODS: Among 1603 participants, from May 1996 to December 2005,
      risk factors for initiation of cocaine injection among baseline heroin users were
      determined by Cox proportional hazards regression and correlates of daily cocaine
      injection by generalized estimating equations. FINDINGS: Of the 238 individuals
      who had never injected cocaine, 200 (84%) had at least one follow-up visit and
      121 (61%) consequently initiated into cocaine injection, yielding an incidence
      density of initiation into cocaine injection of 21.9% (95% confidence interval
      (CI): 17.9-25.8) per 100 person-years. In a multivariate model, Downtown Eastside
      (DTES) residence (adjusted hazard ratio (AHR)=2.46, 95% CI: 1.68-3.60),
      incarceration (AHR=1.50, 95% CI: 1.01-2.24), requiring help injecting (AHR=1.57,
      95% CI: 0.99-2.49), and binge drug use (AHR=1.82, 95% CI: 1.22-2.73) remained
      associated with initiation into cocaine injection. DTES residence (adjusted odds
      ratio (AOR)=1.99, 95% CI: 1.62-2.46), unstable housing (AOR=1.28, 95% CI: 1.04
      1.53), incarceration (AOR=1.29, 95% CI: 1.04-1.60), sex trade involvement
      (AOR=1.46, 95% CI: 1.15-1.85), requiring help injecting (AOR=2.11, 95% CI: 1.73
      2.58)), borrowing syringes (AOR=1.81, 95% CI: 1.35-2.43) and binge drug use
      (AOR=2.16, 95% CI: 1.81-2.58) were independently associated with daily cocaine
      injection. CONCLUSIONS: The baseline prevalence and subsequent incidence of
      initiation into cocaine injection was high. Daily cocaine injection was
      independently associated with a number of health and social harms, including
      elevated HIV risk behavior.

PMID- 18805657
TI  - Estimation of gestational age in Egyptian native goats by ultrasonographic
      fetometry.
AB  - The main aim of the present study was to estimate the gestational age of Egyptian
      goats by B-mode ultrasound measurement of embryonic or fetal parts throughout
      pregnancy. Trans-rectal (TR) ultrasonography (7 MHz) was carried out on 15
      pregnant Egyptian does at Day 10 post mating on alternate days until Day 25 and
      then once at 3-5-day intervals until Day 50. Trans-abdominal (TA) ultrasonography
      (3.5-5 MHz) was carried out on the same animals from Days 25 to 130 at 3-5-day
      intervals. After imaging the embryo or the fetus, the following parameters were
      measured: length of the embryo or fetus (CRL), heart rate (FHR), biparital
      diameter (BPD), trunk diameter (TD), placentome size (PS), umbilical cord
      diameter (UCD) and femur length (FL). The average of days at which the embryonic
      vesicle was first determined by TR and TA ultrasonography was 16.98+/-1.97 and
      27.87+/-3.48, respectively. The embryo proper with a beating heart was first
      determined by TR and TA ultrasonography at an average of 22.36+/-2.66 and 30.36+/
      4.75 days, respectively. All the fetal measures were significantly (P<0.0001)
      correlated with the gestational age. With the exception of fetal heart rate
      (R(2)=0.551), all the measured fetal structures were highly correlated (R(2)> or
      =90) with the gestational age. In conclusion, the age of embryo or fetus in
      Egyptian does can be estimated by ultrasound measuring the crown rump length,
      biparital diameter, trunk diameter, placentome size, umbilical cord diameter and
      femur length.

PMID- 18805656
TI  - Predictors of outcome for short-term medically supervised opioid withdrawal
      during a randomized, multicenter trial of buprenorphine-naloxone and clonidine in
      the NIDA clinical trials network drug and alcohol dependence.
AB  - Few studies in community settings have evaluated predictors, mediators, and
      moderators of treatment success for medically supervised opioid withdrawal
      treatment. This report presents new findings about these factors from a study of
      344 opioid-dependent men and women prospectively randomized to either
      buprenorphine-naloxone or clonidine in an open-label 13-day medically supervised
      withdrawal study. Subjects were either inpatient or outpatient in community
      treatment settings; however not randomized by treatment setting. Medication type
      (buprenorphine-naloxone versus clonidine) was the single best predictor of
      treatment retention and treatment success, regardless of treatment setting.
      Compared to the outpatient setting, the inpatient setting was associated with
      higher abstinence rates but similar retention rates when adjusting for medication
      type. Early opioid withdrawal severity mediated the relationship between
      medication type and treatment outcome with buprenorphine-naloxone being superior
      to clonidine at relieving early withdrawal symptoms. Inpatient subjects on
      clonidine with lower withdrawal scores at baseline did better than those with
      higher withdrawal scores; inpatient subjects receiving buprenorphine-naloxone did
      better with higher withdrawal scores at baseline than those with lower withdrawal
      scores. No relationship was found between treatment outcome and age, gender,
      race, education, employment, marital status, legal problems, baseline depression,
      or length/severity of drug use. Tobacco use was associated with worse opioid
      treatment outcomes. Severe baseline anxiety symptoms doubled treatment success.
      Medication type (buprenorphine-naloxone) was the most important predictor of
      positive outcome; however the paper also considers other clinical and policy
      implications of other results, including that inpatient setting predicted better
      outcomes and moderated medication outcomes.

PMID- 18805658
TI  - Long-term cryopreservation of sperm from Mandarin fish Siniperca chuatsi.
AB  - In order to develop cryopreservation techniques for long-term preserving the
      sperm of Mandarin fish Siniperca chuatsi, we examined the effects of various
      extender and cryopreservation on post-thaw motility. We found the optimal
      freezing procedures for the Mandarin fish sperm is diluting the semen in D-15
      extender, chilling it to 4 degrees C, adding ME2SO to a final concentration of
      10% (v/v), then transferring the semen in cryotubes, holding the cryotubes for 10
      min at 6 cm (about -180 degrees C) above the surface of liquid nitrogen, for 5
      min on the surface of liquid nitrogen, and finally plunged into liquid nitrogen.
      After thawed at 37 degrees C for 60s, the sperm had the highest post-thaw
      motility (96.00+/-1.73%). The optimal fertilization procedures for the frozen
      sperm is mixing the eggs with sperm, then adding 1 ml of swimming medium (SM=45
      mM NaCl+5 mM KCl+20mM Tris-HCl, pH 8.0) immediately. At the sperm/egg ratio of
      100,000:1, the fertilization rate and the hatching rate of the frozen sperm
      cryopreserved for 1 week or 1 year in liquid nitrogen (66.01+/-5.14% and 54.76+/
      4.40% & 62.97+/-14.28% and 52.58+/-11.17%) were similar to that of fresh sperm
      (69.42+/-8.11% and 59.82+/-5.27%) (p>0.05). This is the first report that the
      Mandarin fish (S. chuatsi) sperm can successfully fertilized eggs after long-term
      cryopreservation.

PMID- 18805659
TI  - Rabbit sperm cryopreservation: a review.
AB  - Sperm cryopreservation is a great challenge, since many sperm are irreversibly
      damaged or present altered functionality after the whole process. Although
      components of extenders for sperm cryopreservation are quite similar between
      species, sperm from each of the species present peculiarities that force
      researchers to optimize the extenders and protocols for each particular species.
      In this review, information related to rabbit sperm cryopreservation is compiled.
      The topics discussed include the extenders and protocols developed for rabbit
      sperm cryopreservation, as well as fertility data obtained after artificial
      insemination with cryopreserved sperm and factors that may have an impact on the
      results obtained. In addition, suggestions for improving the results after
      cryopreservation of rabbit sperm are also proposed.

PMID- 18805660
TI  - Effects of biostimulation and nutritional supplementation on pubertal age and
      pregnancy rates of Nelore heifers (Bos indicus) in a tropical environment.
AB  - To determine effects of biostimulation (BIO) and dietary supplementation (BIO+S)
      on pubertal age and pregnancy rates, Nelore heifers (n=392) were randomly
      assigned to one of four treatment groups (n=98/group). All animals were in
      tropical environmental conditions, in the middle-west region of Brazil, grazing
      in pastures of Brachiaria brizantha, cv. Marandu; Panicum Maximum, cv. Tanzania
      and Brachiaria humidicula. The heifers of the BIO group were kept in the presence
      of bulls while being maintained on pasture; the animals in the BIO+S group were
      kept in the presence of bulls while being managed on pasture and were fed a diet
      with greater energy and protein content to produce 0.49 kg of BW gain/day; the
      animals in control group (the NBIO) were kept away from bulls and under pasture
      conditions; and the animals in the NBIO+S group were kept away from bulls, were
      maintained on pasture, and were fed the same diet as the BIO+S group. Heifers
      were bred at 22-23 months of age, and pregnancy diagnosis was made 45 days after
      the end of the breeding season. There were differences (P<0.05) between groups
      regarding pubertal heifers up to 19 months (NPH), final body weight (FBW) and
      pregnancy rates (P<0.01), with an advantage for the animals in the BIO and BIO+S
      groups. Although the effect of a diet with greater protein and energy content was
      not clear in this experiment, the exposure of heifers to a male during the
      prepubertal period decreased age at the first breeding season, resulting in a
      significant reduction in age of first pregnancy in Nelore heifers kept under
      extensive management systems in a tropical environment.

PMID- 18805661
TI  - The first 30 years of MATURITAS.

PMID- 18805662
TI  - A French prospective observational study of the treatment of chronic hepatitis C
      in drug abusers.
AB  - The objective of this prospective, multicenter, observational study was to
      evaluate healthcare for hepatitis C virus (HCV)-infected drug abusers in France
      and to determine predictors of successful therapeutic intervention. A total of
      170 drug users were recruited from 40 French centers. Three centers recruited 66
      participants (38.8%), and one to eight patients each were enrolled from 37 other
      centers (n=104). A sustained viral response (SVR) was seen in 65 (38.2%)
      patients. SVR rates were significantly higher in compliant than in non-compliant
      patients (43.5% versus 23.9%; P=0.019), in patients from high- rather than low
      recruiting centers (54.5% versus 27.9%; P<0.001) and in patients receiving
      Buprenorphine rather than methadone (48.1% versus 21.8%; P=0.001). In patients,
      who completed both the treatment and follow-up (n=94), SVR rate was 57.4%.
      Buprenorphine substitution therapy and genotypes 2 or 3 HCV infection were
      associated with significantly higher rates of SVR (P<0.01, for both comparisons).
      In conclusion, successful care of hepatitis requires an active treatment policy
      of every center toward drug addicts. Additional studies are needed to explore the
      difference in SVR with methadone versus Buprenorphine therapy.

PMID- 18805663
TI  - Heartbeat-related displacement of the thoracic aorta in patients with chronic
      aortic dissection type B: quantification by dynamic CTA.
AB  - PURPOSE: The purpose of this study was to characterize the heartbeat-related
      displacement of the thoracic aorta in patients with chronic aortic dissection
      type B (CADB). MATERIALS AND METHODS: Electrocardiogram-gated computed tomography
      angiography was performed during inspiratory breath-hold in 11 patients with
      CADB: Collimation 16 mm x 1 mm, pitch 0.2, slice thickness 1mm, reconstruction
      increment 0.8 mm. Multiplanar reformations were taken for 20 equidistant time
      instances through both ascending (AAo) and descending aorta (true lumen, DAoT;
      false lumen, DAoF) and the vertex of the aortic arch (VA). In-plane vessel
      displacement was determined by region of interest analysis. RESULTS: Mean
      displacement was 5.2+/-1.7 mm (AAo), 1.6+/-1.0 mm (VA), 0.9+/-0.4 mm (DAoT), and
      1.1+/-0.4mm (DAoF). This indicated a significant reduction of displacement from
      AAo to VA and DAoT (p<0.05). The direction of displacement was anterior for AAo
      and cranial for VA. CONCLUSION: In CADB, the thoracic aorta undergoes a heartbeat
      related displacement that exhibits an unbalanced distribution of magnitude and
      direction along the thoracic vessel course. Since consecutive traction forces on
      the aortic wall have to be assumed, these observations may have implications on
      pathogenesis of and treatment strategies for CADB.

PMID- 18805664
TI  - Relevant traumatic injury of the knee joint-MRI follow-up after 7-10 years.
AB  - OBJECTIVE: To evaluate prospectively the history of relevant traumatic knee
      injuries at least 7 years after trauma by MRI focusing on the development of
      degenerative changes. MATERIALS AND METHODS: Seventeen patients without baseline
      degenerative changes had a follow-up knee MRI several years after relevant knee
      injury (interval baseline-follow-up was 9.1 years, S.D. +/-1.3 years). Relevant
      knee injury was defined as complete cruciate or collateral ligament rupture,
      traumatic meniscal tear or osteochondral injury. Baseline MRI examinations were
      evaluated for traumatic ligamentous, chondral, meniscal and osseous lesions.
      Follow-up MRIs were evaluated for ligamentous and meniscal status, articular
      surface and incidence of degenerative changes such as cartilage loss, osteophytes
      and bone marrow lesions. RESULTS: Among the 11 patients who had a complete
      rupture of the ACL at baseline, 3 (27.3%) presented with cartilage loss. Among
      the eight patients who had suffered a post-traumatic meniscal tear at baseline,
      four (50%) presented with cartilage loss at follow-up. Among the five patients
      who had an osteochondral fracture at baseline, two (40%) presented with cartilage
      loss at follow-up imaging. Cartilage loss in all cases was observed adjacent to
      the subregions where meniscal damage and/or osteochondral incongruence was/were
      present at follow-up imaging. CONCLUSION: We hypothesize that the post-traumatic
      or postsurgical meniscal damage and the persistence of an irregular articular
      surface may have played a role in the subsequent loss of cartilage in our patient
      population.

PMID- 18805665
TI  - Assessment of liver phagocytic activity using EPR spectrometry and imaging.
AB  - The aim of the present study was to evaluate the usefulness of electron
      paramagnetic resonance (EPR) spectroscopy and imaging in assessing the phagocytic
      activity of the liver after administration of India ink. We conducted experiments
      on livers from control rodents and from rodents in which the Kupffer cell
      population had been depleted by pretreatment with gadolinium chloride. The EPR
      signal intensity recorded in liver homogenates was about two times lower in
      GdCl(3) treated rats than in control rats. EPR imaging carried out on precision
      cut liver slices indicated a good correlation between the depletion of Kupffer
      cells and the EPR signal intensity.

PMID- 18805666
TI  - Nonlinear blood oxygen level-dependent responses for transient activations and
      deactivations in V1 - insights into the hemodynamic response function with the
      balloon model.
AB  - We report studies of the nonlinear nature of blood oxygen level-dependent (BOLD)
      responses to short transient deactivations in human visual cortex. Both
      functional magnetic resonance imaging (fMRI) and near-infrared spectroscopy
      (NIRS) have been used to compare and contrast the hemodynamic response functions
      (HRFs) associated with transient activation and deactivation in primary visual
      cortex. We show that signal decreases for short duration deactivations are
      smaller than corresponding signal increases in activation studies. Moreover, the
      standard balloon model of BOLD effects may be modified to account for the
      observed nonlinear nature of deactivations by appropriate changes to simple
      hemodynamic parameters without recourse to new assumptions about the nature of
      the coupling between activity and oxygen use.

PMID- 18805667
TI  - Multiresponse optimization of the properties of albendazole-chitosan
      microparticles.
AB  - The loading of albendazole into biodegradable polymeric microparticles provides
      an attractive alternative to improve the drug dissolution rate. Experimental
      design and optimization techniques were implemented for the development of
      albendazole-chitosan microparticles using the ionic interaction method. The
      effect of seven different factors (chitosan concentration, pH of chitosan
      solution, stirring rate, stirring time, temperature, ionic agent and pH of ionic
      solutions) were studied on six responses: the yield, pH, morphology, size,
      dissolution rate and encapsulation efficiency of the microparticles. During the
      screening phase, the factors were evaluated at three levels each, in order to
      identify those which exert a significant effect. Multiple response simultaneous
      optimization by using the desirability function was then used to find
      experimental conditions where the system shows the most adequate results. The
      optimal conditions were found to be: NaOH as ionic agent at a pH value of 13.0,
      chitosan concentration, 0.50% (w/v) at a pH value of 1.0 and stirring rate, 1,000
      rpm.

PMID- 18805668
TI  - Predictors and effectiveness of diabetes self-management education in clinical
      practice.
AB  - OBJECTIVE: To describe the demographic and clinical predictors of attendance at a
      diabetes education center (DEC) for self-management education, and to compare
      subsequent quality of care indicators between attendees and non-attendees.
      METHODS: DEC attendance in 2002 was determined from a written questionnaire
      completed by 781 adults with diabetes across Ontario, Canada. Predictors of
      attendance and quality of care indicators were defined from the questionnaire and
      from linkage with health care administrative data. A multivariate logistic
      regression model was built to find the independent predictors of attendance,
      while quality of care was evaluated using propensity score methods. RESULTS: 30%
      of survey participants reported attending a DEC in 2002. Independent predictors
      of attendance were shorter duration of diabetes, receiving regular primary care,
      receiving regular diabetes specialist care and single marital status. Attendees
      were more likely to receive a retinal screening examination in the following 2
      years than non-attendees. CONCLUSION: Receiving regular primary care was the
      strongest predictor of attending a DEC, suggesting that DECs are not substitute
      providers of diabetes care for people without a regular physician. Increased
      retinal screening among DEC attendees suggests that self-management education
      improved their self-efficacy to ensure adequate screening was performed. PRACTICE
      IMPLICATIONS: The findings characterize the types of people who attend DECs,
      which may lead to identification and targeting of inequities in access. The
      findings also highlight the influence diabetes education can have on quality of
      care in real-world practice.

PMID- 18805669
TI  - Berberine inhibits SDF-1-induced AML cells and leukemic stem cells migration via
      regulation of SDF-1 level in bone marrow stromal cells.
AB  - Berberine plays a prominent role on the control of tumor cell invasion and
      migration. SDF-1 is a homeostatic chemokine that signals through CXCR4 which is
      expressed by hematopoietic tumor cells. The SDF-1/CXCR4 axis is involved in the
      migration process of leukemic cells. In this study, we investigated the effects
      of berberine on the SDF-1-induced HL-60 cells, primary acute myeloid leukemia
      (AML) cells and leukemic stem cells (LSCs) migration. Transwell migration
      chambers (8 microm) were used to assess the role of berberine on leukemic cell
      migration; Flow cytometry was used to analyze the role of berberine on the CXCR4
      expression; SDF-1 protein level secreted by bone marrow stromal cells (BMSCs) was
      evaluated by ELISA. Results demonstrated that berberine could partly inhibit SDF
      1-induced AML cells as well as LSCs migration. Berberine could reduce SDF-1
      protein level secreted by BMSCs in the microenvironment but not affect CXCR4
      expression on HL-60 cell membrane, and we hypothesized that berberine could
      inhibit AML cells migration partly by reducing the secreting of SDF-1 by BMSCs
      and inhibiting HERG1 K(+) channels of leukemic cells. Therefore, it is speculated
      that berberine might be a potentially effective agent for prevention of leukemia.

PMID- 18805670
TI  - Interactive curved planar reformation based on snake model.
AB  - Visualization of tortuous tissues such as tracheas plays a very important role in
      medical image processing. Displaying them in a curved plane for diagnosis is a
      better function which is called curved planar reformation (CPR). In this
      manuscript, we use snake model to generate contours of tubular structures in all
      slices selected by users of medical volume data sets. Then, centerline of these
      structures can be obtained. CPR of these structures segmented by snake model is
      realized based on the obtained contours and centerlines. We use B-spline to
      generate a contour along tubular structures through points determined by mouse in
      three view planes. An improved method is used to initialize a snake contours
      before using gradient vector flow (GVF) snake model generating the final contour.
      A head aneurysm data set scanned with computed tomography (CT) is used to
      illustrate the performance of our CPR method. Furthermore some enhancements are
      introduced to our method: adjustment of window width and window level, rotating
      CPR.

PMID- 18805671
TI  - Evidence for reduced neuronal somal size within the insular cortex in
      schizophrenia, but not in affective disorders.
AB  - The insular cortex is a paralimbic area of the brain thought to have important
      roles in sensory integration, auditory hallucinations and language. Both
      structural and functional MRI studies have revealed that this brain area is
      abnormal in both size and activity in schizophrenia. Further investigation of
      this region at the cellular level in schizophrenia has not been carried out. In
      the current study, we conducted a stereological examination of neuronal and glial
      size and density in layers 2 and 3 of the dorso-caudal region of the insular
      cortex in 15 schizophrenic, 15 bipolar, 15 unipolar and 15 control patients.
      These cortical layers are candidate layers based on previous cytoarchitectual
      investigations. Statistical analysis (ANCOVA, correcting for pH, post-mortem
      interval and age) showed decreased neuronal volume in layer 2 in schizophrenia
      (p=0.0008, 16.2% mean reduction). No other significant changes were observed.
      This study thus provides the first evidence of cytoarchitectural abnormality of
      the insular cortex in the pathophysiology of schizophrenia but not mood
      disorders. Further work is needed to investigate the molecular basis for this
      neuronal abnormality in schizophrenia in order to elucidate its role in the
      pathophysiology of schizophrenia.

PMID- 18805672
TI  - Sequence analysis of P21-activated kinase 3 (PAK3) in chronic schizophrenia with
      cognitive impairment.
AB  - The P21-activated kinase PAK3 is critical for cognitive development and
      truncating mutations cause non-syndromic mental retardation (MR). Missense
      mutations are also associated with psychotic disorders, most commonly with
      schizophrenia involving premorbid MR, namely "pfropfschizophrenie". We set out to
      measure the frequency of sequence variants in PAK3 in schizophrenia without
      premorbid MR. We conducted complete gene reseqeuncing of all coding exons and
      exon-intron boundaries in patients with schizophrenia with cognitive impairment
      but without premorbid MR. Deleterious variants in schizophrenia alone were rare
      (<1/159 or 0.6%). Thereby, while PAK3 remains a strong biological candidate in
      psychosis, evidence from human genetics provides strongest support for a link to
      pfropfschizophrenie and not to schizophrenia without premorbid intellectual
      disability.

PMID- 18805673
TI  - Fewer neurological soft signs among first episode psychosis patients with heavy
      cannabis use.
AB  - BACKGROUND: Although neurological soft signs (NSS) have been consistently
      associated with schizophrenia and a variety of risk factors, few studies have
      focused on the association between NSS and environmental factors such as cannabis
      use, particularly in patients with first episode psychosis. METHODS: We
      administered the Neurological Evaluation Scale (NES) to 92 patients during their
      first episode of functional psychosis. Psychopathology was assessed with the
      Positive And Negative Syndrome Scale (PANSS) and the family history of psychotic
      disorder was established on the basis of the Family Interview for Genetic Studies
      (FIGS). We also assessed lifetime cannabis and cocaine use utilizing that
      specific section of the Composite International Diagnostic Interview. The outcome
      variable was the presence of high NSS, defined by a score above the median split
      of the NES score (>21). RESULTS: Most patients (80/92, 87%) presented a non
      affective psychosis. The presence of high NSS showed a significant independent
      association with not having been a heavy cannabis user (OR=8.3; 95% CI, 2.4
      33.3), family history of psychosis (OR=4.3; 95% CI, 1.2-14.9), male sex (OR=4.0;
      95% CI, 1.2-14.0), lower score in verbal fluency and higher score in negative
      symptoms (both p<0.01). CONCLUSION: Our cross-sectional results support the
      hypothesis that potentially different pathways associated with the emergence of
      first episode psychosis may exist, including neurological premorbid alteration
      and environmental cannabis abuse.

PMID- 18805674
TI  - Emotional intelligence in schizophrenia.
AB  - BACKGROUND: Deficits in emotion perception have been extensively documented in
      schizophrenia and are associated with poor psychosocial functioning. However,
      little is known about other aspects of emotion processing that are critical for
      adaptive functioning. The current study assessed schizophrenia patients'
      performance on a theoretically-based, well-validated, multidimensional measure of
      emotional intelligence, the Mayer-Salovey-Caruso Emotional Intelligence Test
      (Mayer, J.D., Salovey, P., Caruso, D.R., 2002. Mayer-Salovey-Caruso Emotional
      Intelligence Test (MSCEIT): User's Manual. Multi-Health Systems, Inc., Toronto,
      Ontario). METHODS: 50 schizophrenia outpatients and 39 non-psychiatric controls
      completed the MSCEIT, a performance measure comprised of subtests that assess
      four components (branches) of emotional intelligence: Identifying, Using,
      Understanding, and Managing Emotions. Among patients, associations between MSCEIT
      scores and measures of clinical symptoms as well as functional outcome were
      evaluated. RESULTS: The MSCEIT demonstrated good psychometric properties in both
      groups. Schizophrenia patients performed significantly worse than controls on the
      total MSCEIT score, and on three of the four subtests: Identifying,
      Understanding, and Managing Emotions. Among patients, lower MSCEIT scores
      significantly correlated with higher negative and disorganized symptoms, as well
      as worse community functioning. CONCLUSIONS: The MSCEIT is a useful tool for
      investigating emotion processing in schizophrenia. Individuals with schizophrenia
      demonstrate deficits across multiple domains of emotion processing. These
      deficits have significant links with clinical symptoms of schizophrenia and with
      how patients function in their daily lives. Further research is required to
      understand the links between emotional intelligence, clinical symptoms, and
      functional outcome in schizophrenia.

PMID- 18805675
TI  - Evidence for the presence of R250G mutation at the ATPase domain of topoisomerase
      II in an arsenite-resistant Leishmania donovani exhibiting a differential drug
      inhibition profile.
AB  - Resistance to operational drugs is a major barrier to successful antileishmanial
      chemotherapy that demands development of novel drug intervention strategies based
      on rational approaches. Model drug resistance phenotypes, such as arsenite
      resistance used in the current study, facilitate our understanding of the
      mechanism of drug resistance and assist in identifying new drug target(s). The
      current study was undertaken to investigate the sensitivity of topoisomerase II
      (topo II) of arsenite-sensitive (Ld-Wt) and -resistant (Ld-As20) Leishmania
      donovani to antileishmanial/anti-topo II agents. The effect of
      antileishmanial/anti-topo II drugs on partially purified topo II enzyme from Ld
      Wt and Ld-As20 revealed differential inhibition of topo II decatenation activity
      for the two strains, with a lower amount of drug required to inhibit activity by
      50% in Ld-Wt compared with Ld-As20. Comparison of topo II sequences from both
      strains indicated a point mutation, R250G, in the ATPase domain of the resistant
      strain. Furthermore, the Arg-250 of the ATPase domain of topo II was observed to
      be conserved throughout different species of Leishmania. Variation in the topo II
      gene sequence between Ld-Wt and Ld-As20 is envisaged to be responsible for the
      differential behaviour of the enzymes from the two sources.

PMID- 18805676
TI  - VIM-5 metallo-beta-lactamase-producing Pseudomonas putida from Turkey.

PMID- 18805677
TI  - Variations in circulating cytokine levels during 52 week course of treatment with
      SSRI for major depressive disorder.
AB  - Major depressive disorder (MDD) is a psychiatric condition characterized by
      hypercortisolism and variations in circulatory cytokines. Previously it has been
      reported that administration of selective serotonin reuptake inhibitors (SSRI) in
      MDD patients modify cortisol and cytokine levels but these studies only evaluated
      changes over a short time period. This work reports the long-term effects of
      administration of SSRI on the cortisol levels and pro-/anti-inflammatory cytokine
      profile in a group of MDD patients treated for 52 weeks. A total of 31 patients
      diagnosed with MDD received anti depressant treatment with SSRI. HDRS and BDI
      were administered over a year, and levels of interleukin IL-1beta, IL-10, IL-2,
      IFN-gamma, IL-4, IL-13, and 24-h urine cortisol were determined at weeks (W) 0,
      5, 20, 36 and 52 of treatment. Before treatment we found high levels of cortisol,
      IL-4, IL-13 (Th2) and IL-10 in MDD patients when compared with healthy
      volunteers. At W20 psychiatric scales indicated a remission of the depressive
      episode concomitantly with increments in IL-2 and IL-1beta but without changes in
      cortisol. Towards the end of the treatment (W52) we observed a significant
      reduction (p<0.01) in cortisol levels, with an increment in IL-1beta and IFN
      gamma and a decrease in Th2 cytokines. Our results suggest that depressed
      patients only reach a partial reestablishment of HPA axis function after the long
      term administration of SSRI.

PMID- 18805678
TI  - Antidepressants alleviate the impact of reinforcer downshift.
AB  - Depressive disorder is associated with problems of coping with life's
      difficulties, including episodes of frustration and disappointment, operationally
      defined as an unexpected reinforcer omission or a reduction of reinforcer
      magnitude. In a novel model aimed at detecting potential antidepressants, rats
      were trained in the operant task under progressive ratio schedule of
      reinforcement with the break point (BP, the value of the last completed response
      ratio) as a behavioral endpoint. In the main experiment, a 32% sucrose solution
      was initially used as the reinforcer. Once the stable responding was achieved,
      for the following 5 days animals were treated once daily with the experimental
      drugs, and were offered a 4% sucrose solution instead. In vehicle-treated
      controls, the reduction of sucrose concentration resulted in a decrease in
      responding from a BP of about 40 (totaling 166 responses) to a BP of about 9
      (totaling 22 responses). Chlordiazepoxide (4 and 8 mg/kg), fluoxetine (3 mg/kg),
      citalopram (6 mg/kg) and cocaine (2.5 and 5 mg/kg) markedly inhibited this
      response decrement, while fluoxetine (6 mg/kg) augmented it. Neither desipramine
      (1-6 mg/kg) nor morphine (1-5 mg/kg) affected responding under the reduced
      sucrose concentration condition. In the control experiment, the rats have never
      been offered 32% sucrose solution but their responding was always maintained by
      4% sucrose. Under these unchanged conditions, only cocaine (5 mg/kg) affected
      (increased) responding. The present results suggest that the antidepressants
      selectively inhibiting serotonin reuptake and a benzodiazepine anxiolytic but not
      psychostimulant cocaine may specifically protect animals from the effects of a
      reinforcer downshift.

PMID- 18805679
TI  - Selenium nanoparticles fabricated in Undaria pinnatifida polysaccharide solutions
      induce mitochondria-mediated apoptosis in A375 human melanoma cells.
AB  - Selenium nanoparticle (Nano-Se) is a novel Se species with novel biological
      activities and low toxicity. In the present study, we demonstrated a simple
      method for synthesis of size-controlled Nano-Se by adding Undaria pinnatifida
      polysaccharides to the redox system of selenite and ascorbic acid. A panel of
      four human cancer cell lines was shown to be susceptible to Nano-Se, with IC(50)
      values ranging from 3.0 to 14.1 microM. Treatment of A375 human melanoma cells
      with the Nano-Se resulted in dose-dependent cell apoptosis as indicated by DNA
      fragmentation and phosphatidylserine translocation. Further investigation on
      intracellular mechanisms found that Nano-Se treatment triggered apoptotic cell
      death in A375 cells with the involvement of oxidative stress and mitochondrial
      dysfunction. Our results suggest that Nano-Se may be a candidate for further
      evaluation as a chemopreventive and chemotherapeutic agent for human cancers,
      especially melanoma cancer.

PMID- 18805680
TI  - Growing hyperbranched polyglycerols on magnetic nanoparticles to resist
      nonspecific adsorption of proteins.
AB  - Hyperbranched polyglycerols were grown from magnetic nanoparticles (MNPs) via
      surface-initiated anionic ring-opening polymerization of glycidol. The modified
      MNPs were characterized by using TEM, XPS, TGA and FTIR. Hyperbranched
      polyglycerols resist the nonspecific adsorption of proteins on magnetic
      nanoparticles. The capability of hyperbranched polyglycerols is comparable
      favorably with the performance of methyloxy poly(ethylene glycol) (a linear mPEG
      with a molecular weight of 750) in resisting the adsorption of proteins.

PMID- 18805681
TI  - Obstructive sleep apnoea correlates with C-reactive protein in obese Asian
      Indians.
AB  - BACKGROUND: C-reactive protein (CRP), a marker of systemic inflammation, is an
      important predictor of future cardiovascular events. Whether the relationship of
      obstructive sleep apnoea (OSA) and CRP is independent of adiposity, needs to be
      investigated. OBJECTIVE: To investigate the association of CRP levels with OSA in
      the obese and their comparison with lean subjects without OSA in Asian Indians
      residing in India. METHODS AND RESULTS: One hundred and eight obese subjects (62
      treatment naive obese subjects with OSA [cases] and 46 obese subjects without OSA
      [obese controls]) and 26 lean control subjects without OSA were studied. The
      subjects were without any apparent inflammatory disease. Obese subjects were
      matched for body mass index (BMI) and percentage body fat (%BF). Assessment
      included anthropometry, lipid profile and high sensitivity CRP (hs-CRP) levels.
      Mean hs-CRP levels were significantly higher in cases [(3.6+/-2.0) mg/l than in
      obese controls (1.4+/-1.4) mg/l, p<0.001)] and in lean controls [(0.93+/-0.71)
      mg/l, p>0.05]. CONCLUSIONS: In this sample of Asian Indians, subjects with OSA
      had significantly higher CRP levels. These levels were directly proportional to
      the increase in severity of OSA and it was independent of adiposity. These
      observations have important implications for future cardiovascular risk in Asian
      Indians with OSA.

PMID- 18805682
TI  - Potential prebiotic activity of oligosaccharides obtained by enzymatic conversion
      of durum wheat insoluble dietary fibre into soluble dietary fibre.
AB  - BACKGROUND AND AIMS: Epidemiological evidence indicates that cereal dietary fibre
      (DF) may have several cardiovascular health benefits. The underlying mechanisms
      have not yet been elucidated. Here, the potential nutritional effects of physico
      chemical properties modifications of durum wheat dietary fibre (DWF) induced by
      enzyme treatment have been investigated. METHODS AND RESULTS: The conversion of
      the highly polymerised insoluble dietary fibre into soluble feruloyl
      oligosaccharides of DWF was achieved by a tailored enzymatic treatment. The in
      vitro fermentation and release of ferulic acid by intestinal microbiota from DWF
      before and after the enzymatic treatment were assessed using a gut model
      validated to mimic the human colonic microbial environment. Results demonstrated
      that, compared to DWF, the enzyme-treated DWF (ET-DWF) stimulated the growth of
      bifidobacteria and lactobacilli. Concurrently, the release of free ferulic acid
      by ET-DWF was almost three times higher respect to the control. No effect on the
      formation of short chain fatty acids was observed. CONCLUSIONS: The conversion of
      insoluble dietary fibre from cereals into soluble dietary fibre generated a gut
      microbial fermentation that supported bifidobacteria and lactobacilli. The
      concurrent increase in free ferulic acid from the enzyme-treated DWF might result
      in a higher plasma ferulic acid concentration which could be one of the reasons
      for the health benefits reported for dietary fibre in cardiovascular diseases.

PMID- 18805683
TI  - Measurement of the intrarenal arterial resistance index for the identification
      and prediction of diabetic nephropathy.
AB  - BACKGROUND AND AIMS: High intrarenal resistance index (RI) predicts renal
      function in several conditions; its use in the prediction of diabetic nephropathy
      (DN) is little explored. We aimed (1) to compare RI in diabetic and non diabetic
      hypertensive patients, and (2) to evaluate whether high RI is associated with
      clinical signs of DN and its progression over time. METHODS AND RESULTS:  DESIGN:
      observational, prospective. PARTICIPANTS: 92 type 2 diabetic patients and 37 non
      diabetic controls aged 40-70, with hypertension and normal renal function. We
      measured ultrasound RI and, among others, creatinine, estimated glomerular
      filtration rate and urinary albumin excretion rate (AER) at baseline and after
      4.5 years follow-up. Progression of albuminuric state (i.e., transition from
      baseline normo-microalbuminuria to follow-up micro-macroalbuminuria) was
      evaluated. RI was significantly higher in diabetic than non-diabetic participants
      (0.69+/-0.05 vs 0.59+/-0.05, p<0.001). Diabetic patients with RI>or=0.73, i.e.,
      above the 80th percentile of the RI distribution, had significantly higher
      baseline AER and a more frequent progression of the albuminuric state compared to
      patients with RI<0.73 (27.7microg/mg [12.1-235.4] vs 15.1microg/mg [8.6-33.4];
      52.9% vs 9.5%, respectively). AER increased significantly from baseline to follow
      up in patients with RI>or=0.73 (from 27.7microg/mg [12.1-235.4] to 265.0microg/mg
      [23.8-1018.1], p<0.01), but not in those with RI<0.73 (from 15.1microg/mg [8.6
      33.4] to 16.1microg/mg [10.7-67.2], ns). OR for progression of albuminuric state,
      adjusted for established predictors of DN, including baseline AER, was 5.01 (1.4
      17.7, 95% CI) for patients with RI>or=0.73 vs <0.73. Findings were confirmed in
      patients with normoalbuminuria at baseline. CONCLUSIONS: In diabetic patients,
      high RI (>or=0.73) is associated with features of DN and its progression over
      time, independent of albuminuria.

PMID- 18805684
TI  - The effect of montelukast on exhaled nitric oxide of alveolar and bronchial
      origin in inhaled corticosteroid-treated asthma.
AB  - BACKGROUND: Inhaled corticosteroid therapy suppresses nitric oxide levels (NO) of
      airway origin but not necessarily NO of alveolar or small airway origin. Systemic
      therapy with an oral anti-leukotriene agent may suppress NO production in distal
      airways and alveoli not reached by inhaled therapy. METHODS: Adult patients with
      mild asthma were treated for 3 weeks with inhaled fluticasone 250 microg twice
      daily then with inhaled fluticasone plus oral montelukast 10 mg daily for 3
      additional weeks. We monitored exhaled NO (eNO), spirometry, lung volumes, and
      asthma symptoms scores at baseline and at the end of each treatment period. In a
      subset of patients, we continued with montelukast monotherapy and repeated these
      measurements. RESULTS: In the 18 patients studied, pulmonary function parameters
      and asthma symptom scores were not altered significantly from baseline by any
      therapy. The total eNO at baseline was 55+/-35.3 ppb, dropping to 28.1+/-15.3 ppb
      (p=0.005) after 3 weeks of fluticasone and to 23.5+/-14 ppb (p=0.001 vs.
      baseline) after the addition of montelukast. The trend towards reduced total eNO
      with the combination therapy vs. monotherapy was not statistically significant.
      Alveolar eNO dropped from 4.2+/-2.4 at baseline to 3.0+/-1.5 (p=0.1) after
      fluticasone and then to 2.2+/-0.9 (p=0.08 vs. baseline) after fluticasone plus
      montelukast, increasing then to 3.8+/-1.8 after montelukast alone (p=0.6 vs.
      baseline). CONCLUSIONS: Leukotriene receptor antagonists administered
      systemically might decrease small airway/alveolar sites of inflammation when
      combined to inhaled corticosteroid therapy.

PMID- 18805685
TI  - Protective effect of docosahexaenoic acid against brain injury in ischemic rats.
AB  - Evidence suggests that inactivation of cell-damaging mechanisms and/or activation
      of cell-survival mechanisms may provide effective preventive or therapeutic
      interventions to reduce cerebral ischemia/reperfusion (I/R) injuries.
      Docosahexaenoic acid (DHA) is an essential polyunsaturated fatty acid in the
      central nervous system that has been shown to possess neuroprotective effects. We
      examined whether different preadministrative protocols of DHA have effects on
      brain injury after focal cerebral I/R and investigated the potential neuroactive
      mechanisms involved. Sprague-Dawley rats were intraperitoneally pretreated with
      DHA once 1 h or 3 days being subjected to focal cerebral I/R or daily for 6 weeks
      before being subjected to focal cerebral I/R. Reduction of brain infarction was
      found in all three DHA-pretreated groups. The beneficial effect of DHA on the
      treatment groups was accompanied by decreases in blood-brain barrier disruption,
      brain edema, malondialdehyde (MDA) production, inflammatory cell infiltration,
      interleukin-6 (IL-6) expression and caspase-3 activity. Elevation of
      antioxidative capacity, as evidenced by decreased MDA level and increased
      superoxide dismutase activity and glutathione level, was detected only in the
      chronic daily-administration group. The two single-administration groups showed
      increased phosphorylation of extracellular-signal-regulated kinase (ERK).
      Elevation of Bcl-2 expression was detected in the chronic daily-administration
      and 3-day-administration groups. In vitro study demonstrated that DHA attenuated
      IL-6 production from stimulated glial cells involving nuclear factor kappaB
      inactivation. Therefore, the data suggest that the neuroprotective mechanisms of
      DHA pretreatment are, in part, mediated by attenuating damaging mechanisms
      through reduction of cytotoxic factor production and by strengthening survival
      mechanisms through ERK-mediated and/or Bcl-2-mediated prosurvival cascade.

PMID- 18805686
TI  - Why don't out-of-treatment individuals enter methadone treatment programmes?
AB  - BACKGROUND: Despite the proven effectiveness of methadone treatment, the majority
      of heroin-dependent individuals are out-of-treatment. METHODS: Twenty-six opioid
      dependent adults who met the criteria for methadone maintenance who were neither
      seeking methadone treatment at the time of study enrollment, nor had participated
      in such treatment during the past 12 months, were recruited from the streets of
      Baltimore, Maryland through targeted sampling. Ethnographic interviews were
      conducted to ascertain participants' attitudes toward methadone treatment and
      their reasons for not seeking treatment. RESULTS: Barriers to treatment entry
      included: waiting lists, lack of money or health insurance, and requirements to
      possess a photo identification card. For some participants, beliefs about
      methadone such as real or rumored side effects, fear of withdrawal from methadone
      during an incarceration, or disinterest in adhering to the structure of treatment
      programmes kept them from applying. In addition, other participants were not
      willing to commit to indefinite "maintenance" but would have accepted shorter
      time-limited methadone treatment. CONCLUSION: Barriers to treatment entry could
      be overcome by an infusion of public financial support to expand treatment
      access, which would reduce or eliminate waiting lists, waive treatment-related
      fees, and/or provide health insurance coverage for treatment. Treatment
      programmes could overcome some of the barriers by waiving their photo I.D.
      requirements, permitting time-limited treatment with the option to extend such
      treatment upon request, and working with corrections agencies to ensure continued
      methadone treatment upon incarceration.

PMID- 18805687
TI  - Diamond-like carbon (DLC) microelectrode for electrochemical ELISA.
AB  - A diamond-like carbon (DLC) microelectrode was applied to commercial ELISA kits
      for medical diagnosis of HIV (human immunodeficiency virus), HBV (human hepatitis
      B virus), HCV (human hepatitis C virus). In this work, quantification of oxidized
      3,3',5,5'-tetramethylbenzidine (TMB) was carried out by using a microelectrode
      made of boron-doped DLC and cyclic voltammetric analysis method without the
      conventional quenching step which uses sulfuric acid. The microelectrode provided
      well-known step-shaped graphs, and limit of detection could be improved by clear
      determination of electrochemical oxidative and reductive peaks. To demonstrate
      the applicability of DLC microelectrode to conventional ELISA kits, commercial
      ELISA kits for detection of HIV antigen, HBV antigen and HCV antigen were also
      tested. These results proved that the applicability of DLC microelectrode to
      practical detection is feasible.

PMID- 18805688
TI  - A prototype microfluidic chip using fluorescent yeast for detection of toxic
      compounds.
AB  - A microfluidic chip has been developed to enable the screening of chemicals for
      environmental toxicity. The microfluidic approach offers several advantages over
      macro-scale systems for toxicity screening, including low cost and flexibility in
      design. This design flexibility means the chips can be produced with multiple
      channels or chambers which can be used to screen for different toxic compounds,
      or the same toxicant at different concentrations. Saccharomyces cerevisiae
      containing fluorescent markers are ideal candidates for the microfluidic
      screening system as fluorescence is emitted without the need of additional
      reagents. Microfluidic chips containing eight multi-parallel channels have been
      developed to retain yeast within the chip and allow exposure of them to toxic
      compounds. The recombinant yeast used was GreenScreentrade mark which expresses
      green fluorescent proteins when is exposed to genotoxins. After exposure of the
      yeast to target compounds, the fluorescence emission was detected using an
      inverted microscope. Qualitative and quantitative comparisons of the fluorescent
      emission were performed. Results indicated that fluorescent intensity per area
      significantly increases upon exposure to methyl-methanesulfonate, a well known
      genotoxic compound. The microfluidic approach reported here is an excellent tool
      for cell-based screening and detection of different toxicities. The device has
      the potential for use by industrial manufacturers to detect and reduce the
      production and discharge of toxic compounds, as well as to characterise already
      polluted environments.

PMID- 18805689
TI  - 'Breast awareness' and 'breast self-examination' are not the same. What do these
      terms mean? Why are they confused? What can we do?
AB  - The terms 'breast self-examination' and 'breast awareness' are often used
      loosely, causing general confusion, with potential to cause women harm. To
      explore this confusion, we begin by defining their current meaning. We trace the
      history of these methods of early detection over the last half century, which has
      seen considerable cultural, social and attitudinal changes. Breast self
      examination is not recommended. We caution that uncertainty exists about the
      value of practicing breast awareness: evidence is currently lacking to determine
      whether the benefits outweigh the harms: globally-aware research is needed. We
      believe that a clear and universally agreed definition of the term 'breast
      awareness' is needed, and that the confusion needs to be further exposed and
      debated. Meanwhile, we advocate 'sensible alertness'.

PMID- 18805690
TI  - Synthesis of chimeric tetrapeptide-linked cholic acid derivatives: impending
      synergistic agents.
AB  - Tetrapeptides derived from glycine and beta-alanine were hooked at the C-3beta
      position of the modified cholic acid to realize novel linear tetrapeptide-linked
      cholic acid derivatives. All the synthesized compounds were tested against a wide
      variety of microorganisms (gram-negative bacteria, gram-positive bacteria and
      fungi) and their cytotoxicity was evaluated against human embryonic kidney
      (HEK293) and human mammary adenocarcinoma (MCF-7) cell lines. While relatively
      inactive by themselves, these compounds interact synergistically with antibiotics
      such as fluconazole and erythromycin to inhibit growth of fungi and bacteria,
      respectively, at 1-24 microg/mL. The synergistic effect shown by our novel
      compounds is due to their inherent amphiphilicity. The fractional inhibitory
      concentrations reported are comparable to those reported for Polymyxin B
      derivatives.

PMID- 18805691
TI  - Design and synthesis of reboxetine analogs morpholine derivatives as selective
      norepinephrine reuptake inhibitors.
AB  - As part of a discovery effort aimed at identifying novel norepinephrine reuptake
      inhibitors (NRIs), a number of substituted morpholines were designed and
      synthesized. The target compounds contain vicinal stereogenic centers, and the
      program was greatly facilitated by the adoption of efficient synthetic routes
      which allowed for the late stage incorporation of structural and physicochemical
      diversity into the targets. Structure-activity relationships were developed by
      optimizing individual ring components of the structure for NRI potency and for
      selectivity against other monoamine reuptake transporters. Several novel
      morpholine derivatives with a potent and selective NRI profile are described.

PMID- 18805692
TI  - Synthesis and SAR of analogues of the M1 allosteric agonist TBPB. Part I:
      Exploration of alternative benzyl and privileged structure moieties.
AB  - This Letter describes the first account of the synthesis and SAR, developed
      through an iterative analogue library approach, of analogues of the highly
      selective M1 allosteric agonist TBPB. With slight structural changes, mAChR
      selectivity was maintained, but the degree of partial M1 agonism varied
      considerably.

PMID- 18805693
TI  - Carbonic anhydrase inhibitors: inhibition of Plasmodium falciparum carbonic
      anhydrase with aromatic/heterocyclic sulfonamides-in vitro and in vivo studies.
AB  - A library of aromatic/heterocyclic sulfonamides possessing a large diversity of
      scaffolds has been assayed for inhibition of the carbonic anhydrase (CA, EC
      4.2.1.1) from the malaria parasite Plasmodium falciparum (pfCA). Low micromolar
      and submicromolar in vitro inhibitors were detected, whereas several compounds
      showed ex vivo anti-P. falciparum activity, in cell cultures. One derivative,
      that is, 4-(3,4-dichlorophenylureido)thioureido-benzenesulfonamide was an
      effective in vitro pfCA inhibitor (K(I) of 0.18 microM), inhibited the ex vivo
      growth of P. falciparum with an IC(50) of 1 microM, and was also effective as an
      antimalarial agent in mice infected with P. berghei, an animal model of human
      malaria infection, with an ID(50) of 10 mg/kg (chloroquine as standard showed an
      ID(50) of 5 mg/kg). By inhibiting the first step of pyrimidine nucleotide
      biosyntheses, that is, the CA-mediated carbamoylphosphate biosynthesis,
      sulfonamide inhibitors of the protozoan CAs may have potential for the
      development of novel therapies of human malaria.

PMID- 18805694
TI  - Effect of B-ring substitution pattern on binding mode of propionamide selective
      androgen receptor modulators.
AB  - Selective androgen receptor modulators (SARMs) are essentially prostate sparing
      androgens, which provide therapeutic potential in osteoporosis, male hormone
      replacement, and muscle wasting. Herein we report crystal structures of the
      androgen receptor (AR) ligand-binding domain (LBD) complexed to a series of
      potent synthetic nonsteroidal SARMs with a substituted pendant arene referred to
      as the B-ring. We found that hydrophilic B-ring para-substituted analogs exhibit
      an additional region of hydrogen bonding not seen with steroidal compounds and
      that multiple halogen substitutions affect the B-ring conformation and aromatic
      interactions with Trp741. This information elucidates interactions important for
      high AR binding affinity and provides new insight for structure-based drug
      design.

PMID- 18805695
TI  - Preliminary experience of titanium mesh cages for pathological fracture of middle
      and lower cervical vertebrae.
AB  - The advantages and disadvantages of titanium mesh cages (TMCs) assisted by
      anterior cervical plates (ACPs) for interbody fusion following cervical
      corpectomy were investigated. Between January 2002 and September 2006, 17
      patients with cervical radiculomyelopathy caused by metastasis-induced pathologic
      fractures were selected for anterior corpectomy. TMCs were inserted into the post
      corpectomy defect and stabilized by placement of ACPs filled with Triosite. Post
      operative plain X-ray films indicated maintenance of spinal stability. No
      ceramic, donor site or surgery-related complications were observed. True
      trabeculation was observed in axial and reconstructive CT scans in all surviving
      patients one year after surgery. Neurological recovery, pain control, and good
      quality of life were achieved. Short hospital stays, minimal blood loss, short
      operation times and brief periods of bed confinement were also observed. We
      conclude that a TMC assisted by an ACP is safe and effective for interbody fusion
      following cervical corpectomy for pathological fractures resulting from cervical
      vertebral metastases.

PMID- 18805696
TI  - Discovery of 3-acetyl-4-hydroxy-2-pyranone derivatives and their difluoridoborate
      complexes as a novel class of HIV-1 integrase inhibitors.
AB  - HIV-1 integrase (IN) has emerged as an important therapeutic target for anti-HIV
      drug development. Its uniqueness to the virus and its critical role in the viral
      life cycle makes IN suitable for selective inhibition. The recent approval of
      Raltegravir (MK-0518) has created a surge in interest and great optimism in the
      field. In our ongoing IN drug design research, we herein report the discovery of
      substituted analogs of 3-acetyl-4-hydroxy-2-pyranones and their difluoridoborate
      complexes as novel IN inhibitors. In many of these compounds, complexation with
      boron difluoride increased the potency and selectivity of IN inhibition. Compound
      9 was most active with an IC(50) value of 9 microM and 3 microM for 3'-processing
      and strand transfer inhibition, respectively.

PMID- 18805697
TI  - Synthesis and solution conformation studies of the modified nucleoside N(4),2'-O
      dimethylcytidine (m(4)Cm) and its analogues.
AB  - The dimethylated ribosomal nucleoside m(4)Cm and its monomethylated analogues Cm
      and m(4)C were synthesized. The conformations (syn vs anti) of the three modified
      nucleosides and cytidine were determined by CD and 1D NOE difference
      spectroscopy. The ribose sugar puckers were determined by the use of proton
      coupling constants. The position of modification (e.g., O vs N methylation) was
      found to have an effect on the sugar pucker of cytidine.

PMID- 18805698
TI  - New potent cathepsin G phosphonate inhibitors.
AB  - Cathepsin G is an enzyme with dual chymotrypsin and trypsin-like specificity. As
      a leukocyte proteinase it is involved in the early stages of the immune response.
      In this work the synthesis and inhibitory activity of diaryl phosphonic-type
      irreversible cathepsin G inhibitors are described. Modification of the lead
      structure Z-Phg(P)(OPh)2 (k(obs)/I=91 M(-1)s(-1)) in phenyl ester moieties
      followed by incorporation of the basic functional group into the aromatic side
      chain yielded highly potent cathepsin G inhibitor Z-(4-guanidine)Phg(P)(OC6H4-4-S
      Me)2 with the apparent second-order inhibition value at 15,600 M(-1)s(-1).
      Further elongation of the obtained compound by tripeptide resulted in the
      inhibitor Ac-Phe-Val-Thr-(4-guanidine)Phg(P)(OC6H4-4-S-Me)2 with the highest
      k(obs)/I value ever reported in literature (256,000 M(-1)s(-1)).

PMID- 18805699
TI  - Insights into the mechanism of Na+,K+-ATPase inhibition by 2-methoxy-3,8,9
      trihydroxy coumestan.
AB  - The molecular mechanisms involved in Na+,K+-ATPase inhibition by 2-methoxy-3,8,9
      trihydroxy coumestan were investigated. We show that this compound decreases the
      free sulfydryl groups present in the enzyme and that its inhibitory effect is
      prevented by dithiothreitol and other two sulfydryl containing reagents. We
      propose a redox cycle culminating with the irreversible oxidation of sulfydryl
      groups essential for the catalytic activity of this enzyme and of two other
      related P-type ATPases.

PMID- 18805700
TI  - ICU patient's transfer anxiety: a prospective cohort study.
AB  - OBJECTIVE: The purpose of this study was to quantify the levels of anxiety
      experienced by Intensive Care Unit (ICU) patients just before transfer to the
      ward and then twice after transfer to the ward in order to test the hypothesis
      that anxiety levels would change over the three data collection periods. DESIGN:
      A prospective, repeated measure cohort study. SETTING: A Level 3 ICU in an
      Australian teaching hospital. The ICU had a liaison nurse service Monday to
      Friday but there was no medical emergency team service at the time of the study.
      SUBJECTS: All adult ICU patients who remained in ICU for greater than 24h were
      eligible for the study. MAIN OUTCOME MEASURES: Measurements of anxiety were
      undertaken using self report on the anxiety subscale of Hospital Anxiety and
      Depression Scale (HADS-A) on three occasions; after patients were told of their
      imminent transfer to the ward (Time 1), after 4h on the ward (Time 2) and after
      one night on the ward (Time 3). RESULTS: In the 3 months of study 249 patients
      were admitted to the ICU. However, only 55 (22%) patients were eligible to
      participate and 44 (80% of the eligible patients) consented. Thirty-five patients
      (64% of eligible patients) completed all measurement points and represent the
      final sample. The mean anxiety levels remained low at all measurement points and
      did not change over time. Anxiety was present in six (17%) patients at Time 1, in
      three (6.8%) patients at Time 2, and in two (4.5%) patients at Time 3.
      CONCLUSION: This small study provides a start to the prospective mapping of
      anxiety levels on time of transfer and shortly after transfer from an ICU to the
      wards. It also provides information to researchers who want to examine ICU
      transfer anxiety. By understanding the anxiety experienced by ICU patients,
      nurses are better able to provide psychological support and thus more holistic
      care to this group of patients.

PMID- 18805702
TI  - Infections and cancer: established associations and new hypotheses.
AB  - Around the world, infection is one of the most important causes of cancer. Almost
      one in every five malignancies can be attributed to infectious agents. Among
      infection-related neoplasms, cancers of the stomach, liver and cervix uteri
      detain the highest incidence figures, and are known to be largely attributable to
      Helicobacter pylori, hepatitis B and C viruses, and human papilloma virus,
      respectively. Other infectious organisms can also cause cancer; these include the
      Epstein-Barr virus (nasopharyngeal carcinoma, and different types of lymphoma),
      Human herpes virus-8 (Kaposi's Sarcoma), human T-cell leukemia virus type I
      (leukaemia, lymphoma), liver flukes (cholangiocarcinoma) and schistosomiasis
      (bladder cancer). Infection with human immunodeficiency virus, although strongly
      associated with an excess of cancer incidence at many cancer sites, is probably
      not carcinogenic per se, but acts mainly via immunodeficiency. The burden of
      infection-related cancers is still underestimated worldwide, due to the use of
      conservative population prevalence and risk ratio estimates. Furthermore,
      associations with new infectious agents remain yet to be explored.

PMID- 18805704
TI  - The buzz on fly neuronal remodeling.
AB  - Hormone-dependent rewiring of axons and dendrites is a conserved feature of
      nervous system development and plasticity. During metamorphosis in insects,
      steroid hormones (the ecdysteroids) and terpenoid hormones (the juvenile
      hormones) regulate extensive remodeling of the nervous system. These changes
      retool the nervous system for new behavioral and physiological functions that are
      required for the adult stage of the life cycle. In honey bees and other highly
      social insects, hormones also regulate behavioral changes and neuronal plasticity
      associated with transitions between social caste roles. This review focuses on
      recent work in fruit flies and honey bees that reveals hormonal and molecular
      mechanisms underlying metamorphic and caste-dependent neuronal remodeling, with
      specific emphasis on the role of Kruppel homolog 1.

PMID- 18805703
TI  - Tissue-specific glucocorticoid action: a family affair.
AB  - Glucocorticoids exert a wide variety of physiological and pathological responses,
      most of which are mediated by the ubiquitously expressed glucocorticoid receptor
      (GR). The glucocorticoid response varies among individuals, as well as within
      tissues from the same individual, and this phenomenon can be partially explained
      through understanding the process of generating bioavailable ligand and the
      molecular heterogeneity of GR. This review focuses on the recent advances in our
      understanding of prereceptor ligand metabolism, GR subtypes and GR polymorphisms.
      Furthermore, we evaluate the impact of tissue- and individual-specific diversity
      in the glucocorticoid pathway on human health and disease.

PMID- 18805705
TI  - An improved abnormal toxicity test by using reference vaccine-specific body
      weight curves and histopathological data for monitoring vaccine quality and
      safety in Japan.
AB  - Vaccines differ from other pharmaceutical products. The quality and safety of
      batches are regulated to high standards by national regulatory authorities.
      Various quality control and safety tests have been developed, including the
      abnormal toxicity test (ATT), which is described in the World Health Organization
      (WHO) guidelines and in each country's pharmacopoeia. However, the criteria for
      abnormal results are not well defined in these guidelines. In addition, the
      animal grade to be used in ATT, classified on the basis of microbial
      colonization, was not designated in either guideline. In this study, we report a
      new and improved method of performing ATT, including statistical,
      histopathological analysis and hematological findings. It is based on the
      observation that there are body weight changes characteristic to each vaccine,
      and such standardized changes can be used as references for evaluating test
      vaccines. In addition, histopathological data are useful for determining vaccine
      quality and safety. Combined with histopathological examination, the improved ATT
      will be of great use for evaluating the consistency, quality and safety of
      different batches of vaccine. The results of these analyses were similar using
      either 'clean' or specific pathogen-free guinea pigs.

PMID- 18805706
TI  - Representing metarepresentations: is there theory of mind-specific cognition?
AB  - What cognitive mechanisms underlie Theory of Mind? Some infer domain-specific
      Theory of Mind cognition based the pattern of children diagnosed with autism
      failing the False Belief test but passing the False Photograph test. However, we
      argue that the False Belief test entails various task demands the False
      Photograph task does not, including the necessity to represent a higher-order
      representation (a metarepresentation), thus confounding the inference of domain
      specificity. Instead, a general difficulty that affects representations of
      metarepresentations might account for the seeming domain-specific failure. Here
      we find that False-Belief failing False-Photograph passing children fail the Meta
      Photograph test, a new photograph-domain test that requires subjects to represent
      a metarepresentation. We conclude that people who fail the False Belief test but
      pass the False Photograph test do not necessarily have a content-specific Theory
      of Mind deficit. Instead, the general ability to represent representations and
      metarepresentations might underlie Theory of Mind.

PMID- 18805707
TI  - Maternal and obstetric outcome of women with epilepsy.
AB  - Medical professionals and public are concerned about the complications of
      pregnancy and delivery in women with epilepsy (WWE). PURPOSE: Our aim was to
      prospectively ascertain occurrence of these complications in a cohort of WWE
      enrolled in a pregnancy registry. METHODS: All complications during pregnancy,
      delivery and first 48 h of postpartum period were recorded according to the
      registry protocol. This data were compared with similar statistics (for women
      without epilepsy) from a large teaching hospital. RESULTS: Between April 1998 and
      March 2005, there were 643 completed pregnancies in this registry. (Mean age
      25.7+/-4.43 years; generalized epilepsy 46%; localization related epilepsy 54%;
      primigravida 53%.) Their complications are compared with those of 18,272
      pregnancies managed in the teaching hospital (in parentheses). Spontaneous
      abortions 4.2% (2.38%); medical termination of pregnancies 2.64% (7.71%); anemia
      0.62% (0.22%); gestational diabetes 1.56% (3.09%); pregnancy induced hypertension
      3.89% (6.45%); antepartum hemorrhage 0.93% (1.64%); preterm labor 1.87% (6.12%);
      obstructed labor 0.62% (3%); cesarean section 33.4% (29.5%); assisted delivery
      2.8% (2.68%); postpartum hemorrhage 0.31% (0.64%); peripartum seizures 1.4%
      (0.04%); intrauterine death 1.56% (2.2%); fibroid uterus or ovarian cyst 2.33%
      (0.53%); other medical illness 2.5% (2.15%); TORCH infection 0.31% (0.01%); birth
      weight <2.0 kg 4.19% (7.66%). CONCLUSIONS: There was no significant increase in
      the risk of complications of pregnancy or delivery except for spontaneous
      abortions, anemia, ovarian cyst, fibroid uterus, and seizures in the peripartum
      period which were more frequent in WWE. Frequency of cesarean section is not
      increased in WWE. There is no undue risk to pregnancy and childbirth in most WWE.

PMID- 18805708
TI  - Extramammary Paget's disease of scrotum--report of 25 cases and literature
      review.
AB  - OBJECTIVES: We evaluate the clinical manifestations, management, and prognostic
      characteristics of scrotal extramammary Paget's disease (EMPD). METHODS: The
      study comprised 25 patients with scrotal EMPD at our institute from January 1982
      to February 2005, with all available clinical and pathological data reviewed.
      RESULTS: Of these 25 patients, 1 received radiotherapy and 24 received local wide
      excisions. In 24 operated patients, 7 had local recurrence and/or metastasis of
      groin lymph node. Five of the 7 with recurrence had a positive surgical margin
      postoperatively and they received a second local extensive excision. One of the 7
      with recurrence and metastasis of the groin lymph node had a second local
      extensive excision with groin lymphadenectomy, and the last one who only had
      metastasis of the groin lymph node had a groin lymphadenectomy. Four of 13
      patients with dermal invasion by Paget's cell had metastasis. None of the other
      12 patients without dermal invasion had metastasis. However, there was no
      statistical metastasis rate difference (P = 0.096) between the patients with
      dermal invasion by Paget's cell and without. There was no statistical difference
      (P = 0.947) in mean delay time from onset of symptoms to diagnosis between the 2
      groups either. The follow-up duration varies from 17 to 243 months (mean 119 +
      86.2 months). One patient with stage D died of EMPD of the scrotum. CONCLUSIONS:
      We found that EMPD of the scrotum is usually a slow progressive disease, mainly
      seen in elderly patients, and has a good prognosis when there is noninvasive
      disease. The primary treatment for EMPD of the scrotum is wide surgical excision.
      The key to decreasing tumor recurrence, however, is a precise, preoperative
      histological examination to define the range of the lesion.

PMID- 18805709
TI  - Evaluation of renicapsular involvement in Stages I and II renal cell carcinoma
      from the morphological and prognostic point of view.
AB  - BACKGROUND: Prognostic factors are essential for predicting postsurgical outcome
      in renal cell cancer (RCC). This study aimed to evaluate the prognostic impact of
      renicapsular involvement (RCI; invasion without penetration) in Stage I (pT1N0M0)
      and Stage II (pT2N0M0) RCC and to histomorphologically compare the structure of
      fibrous tumoral capsule with the pattern of RCI, the differentiation of which
      might by challenging in localized RCCs spreading near the renicapsule. MATERIALS
      AND METHODS: We retrospectively investigated a cohort of 635 study group patients
      (396 men and 239 women; mean age: 60.9 years; range: 18-84 years) in terms of
      histomorphology and clinical outcome after surgery (nephrectomy or elective
      nephron-sparing surgery) at Stages I and II RCC (pT1-2N0M0). In 489 patients who
      were still alive at the end of the study, median follow-up was 80 months (mean
      86.1 months). Disease-free survival (DFS) was calculated using the Kaplan Meier
      method. Univariate and multivariate Cox proportional hazards regression models
      were fit to determine possible associations between various parameters and
      survival. Another 55 control group patients (38 men and 17 women) aged between 44
      and 75 years (mean age 61.4 years) with pT3a RCC were analyzed for statistical
      comparison (mean and median follow-up of the survivors were 85.7 and 84 months).
      RESULTS: The 5-year DFS rate for patients with and without RCI was determined to
      be 76.9% and 86.3%, respectively (P < 0.01). Patients with histopathologically
      confirmed RCI appear to have the same adverse prognostic outcome as patients with
      RCC invading perinephric tissue (pT3aN0M0; P = 0.493). Histopathologically,
      fibrous tumoral capsule and RCI conventionally show a different morphology,
      making their separation straightforward. CONCLUSIONS: RCI reflects adverse
      prognostic outcome in surgically treated Stages I and II RCC. It can be
      determined by the pathologist without additional expense in time and cost. Hence,
      clinical pathologists should render a clear statement concerning RCI when
      reporting on small localized RCC specimens in order to provide additional
      prognostic information in individual cases and to facilitate selection of
      appropriate patients to be included in further standardized prospective studies,
      which are required to confirm the prognostic impact of RCI in Stages I and II
      RCC.

PMID- 18805710
TI  - Hypohyperdontia: literature review and report of seven cases.
AB  - Hypodontia in combination with hyperdontia (hypohyperdontia) is a condition of
      mixed numeric variation in the human dentition. A comprehensive review on the
      hypohyperdontia literatures reported prevalence ranges from 0.002% to 3.1%. Our
      seven cases of hypohyperdontia involved both the maxillary and the mandibular
      arches. A traditional narrative review is included to describe the prevalence,
      etiology, and previously reported cases on hypohyperdontia. Furthermore, we opine
      that comprehensive clinical and radiographic examinations are essential for
      recognizing such rare dental anomalies. Judicious use of radiographs not only
      enhances the detection of hypohyperdontia, but also leads to changes in the
      course of management.

PMID- 18805711
TI  - Prevalence of pulp calcifications in patients with Marfan syndrome.
AB  - OBJECTIVE: The purpose of this study was to examine the prevalence of pulp
      calcifications in patients with Marfan syndrome. STUDY DESIGN: The prevalence of
      pulp stones and pulp obliteration was evaluated on bitewing radiographs in 21
      subjects with Marfan syndrome and in 100 healthy controls. RESULTS: Subjects with
      Marfan syndrome older than 30 years of age showed a significantly higher
      prevalence of pulp stones (P = .027) or pulp obliteration (P < .001). Pulp stones
      were present in 20.7% and pulp obliteration was found in 7.9% of the examined
      teeth in this group. Subjects with Marfan syndrome also revealed a significant
      correlation between age and number of teeth with pulp stones or pulp
      obliteration. CONCLUSION: The results of the present study indicate that pulp
      calcifications are frequent findings in subjects with Marfan syndrome. This
      should be taken into consideration in endodontic or orthodontic treatment.

PMID- 18805712
TI  - The negative effect of platelet-rich plasma on the growth of human cells is
      associated with secreted thrombospondin-1.
AB  - OBJECTIVE: Earlier studies have suggested that platelet-rich plasma (PRP)
      enhances oral wound healing because of its concentrated growth factors. Few
      studies have investigated whether negative regulators exist in the PRP and
      influence its biological effects on human wound healing. The aim of this study
      was to investigate whether PRP contains an angiogenesis inhibitor, thrombospondin
      1 (TSP-1), and whether this factor negatively affects human cells associated with
      oral healing in vitro. STUDY DESIGN: Using centrifugation, platelet-poor plasma
      (PPP) and PRP were obtained sequentially from 20 volunteers. We used an Alamar
      Blue assay to compare the proliferation rates of various oral cells, cocultured
      for 6 days with different concentrations of PRP and PPP. The levels of TSP-1 in
      PRP were estimated using ELISA. Finally, we tested the antiproliferative effect
      of purified TSP-1 protein on oral cell cultures. RESULTS: After 6 days of
      incubation, there were significantly more cells in the low-PRP-concentration
      group (<5%) and fewer cells in the high-PRP-concentration group (15%-30%). The
      ELISA showed that the quantities of TSP-1 were approximately 183.3 +/- 21.6
      microg/mL in PRP lysate and 9.7 +/- 1.6 microg/mL in the supernatant of the 30%
      PRP gel. Serial concentrations of exogenous TSP-1, corresponding to those of the
      30% PRP gel, dose-dependently inhibited oral cell proliferation. CONCLUSION:
      Within the limits of this study, the proliferation of oral cells significantly
      decreased when treated with high concentrations of PRP. Abundant secretion of TSP
      1 from concentrated PRP may contribute to the antiproliferative effect.

PMID- 18805713
TI  - Hyrax appliance opening and pattern of skeletal maxillary expansion after
      surgically assisted rapid palatal expansion: a computed tomography evaluation.
AB  - OBJECTIVE: The objective of this study was to evaluate, using computed
      tomography, correlations between Hyrax appliance opening and post-SARPE skeletal
      changes. STUDY DESIGN: Fifteen patients underwent SARPE according to a specific
      protocol and were followed. Linear and angular measurements of the anterior,
      intermediate, and posterior portions of the maxilla were evaluated. The
      correlation between maxillary expansion and appliance opening was investigated.
      RESULTS: Significant overall expansion was observed. In the anterior and
      intermediate portions of the maxilla, the increase in maxillary width was greater
      than that observed in the posterior portion. The degree of appliance opening was
      significantly greater than that of the skeletal expansion. Also, no linear
      correlation between appliance opening and regional maxillary expansion was
      established. CONCLUSION: The transverse expansion of the maxilla was less than
      uniform. The lack of linear correlation between appliance opening and skeletal
      expansion is attributable to multiple factors, including those related to the
      device, the surgical technique, and the craniofacial deformity itself.

PMID- 18805714
TI  - Widening a narrow posterior mandibular alveolus following extirpation of a large
      cyst: a case treated with a titanium mesh-plate type distractor.
AB  - Vertical alveolar augmentation by distraction osteogenesis has become a standard
      pretreatment of dental implants due to the main benefit of lack of donor site
      complications, and many reports have shown its benefit with various types of
      alveolar distractors. However, autogenous bone transplantation and/or guided bone
      regeneration techniques are still the standard treatment for correcting a narrow
      alveolar ridge because of few commercially available distractors for alveolar
      widening. In this article, we treated a case by a mesh-plate type of alveolar
      widening distractor for a narrow posterior mandibular alveolar ridge after
      extirpation of a large jaw cyst.

PMID- 18805715
TI  - Salivary changes and dental erosion in bulimia nervosa.
AB  - OBJECTIVE: Our aim was to study if bulimia nervosa (BN) has an impact on salivary
      gland function and if such changes are related to dental erosion. STUDY DESIGN:
      Twenty women with BN and twenty age- and gender-matched controls participated.
      Flow rate and composition of whole and glandular saliva, as well as feeling of
      oral dryness were measured. Dental erosion was measured on casts. RESULTS:
      Compared with control subjects, unstimulated whole saliva (UWS) flow rate was
      reduced in persons with BN, primarily owing to intake of medication (P = .007).
      No major compositional salivary changes were found. In the BN group, the dental
      erosion score was highest and complaints of oral dryness were more frequent.
      CONCLUSIONS: The BN persons had impaired UWS, mainly owing to medication;
      increased feeling of oral dryness; and more dental erosion. Dental erosion was
      related to the duration of eating disorder, whereas no effect of vomiting
      frequency or intake of acidic drinks on reduced UWS was observed.

PMID- 18805716
TI  - Detection of human cytomegalovirus in dental plaque from individual periodontal
      sites by real-time polymerase chain reaction.
AB  - OBJECTIVE: The aim was to evaluate three primer-probe sets and real-time
      polymerase chain reaction (PCR) for the detection of human cytomegalovirus (HCMV)
      in dental plaque from individual periodontal sites. STUDY DESIGN: Fifty
      subgingival plaque specimens from 13 healthy subjects (on average at least 2
      healthy and 2 periodontal disease sites per subject) and 50 saliva specimens from
      24 subjects, including 16 controls, were assessed using 3 primer-probe sets
      (polymerase [POL], glycoprotein B [gB], and US14) and real-time PCR. Kappa
      statistics were performed to measure agreement between the primer-probe sets.
      RESULTS: There was excellent agreement between the gB and POL primers in the
      detection of HCMV (kappa statistic = 0.85 [95% confidence interval 0.71-0.99]),
      yielding a prevalence of 4% (2 out of 50) at individual periodontal disease sites
      and a similar rate of 8.8% (3 out of 34) in saliva. CONCLUSION: Human
      cytomegalovirus was infrequently detected in dental plaque. Of 3 primer-probe
      sets evaluated, those targeting the POL and gB genes were more accurate in the
      detection of HCMV than that targeting US14.

PMID- 18805717
TI  - Histologic study of the cellular events during rat mandibular distraction
      osteogenesis.
AB  - OBJECTIVE: The cellular events, underlying bone regeneration through rat
      mandibular distraction osteogenesis (DO) was examined using micro computerized
      tomography (microCT), histology, and histochemistry. STUDY DESIGN: After 5-day
      latency, mandibles were distracted at 0.2 mm/12 h for 10 days, and fixed at
      latency 5 days (L5D), distraction 3, 6, 10 days (D3D, D6D, D10D), and
      consolidation 1, 3, 6, 10 weeks (C1W, C3W, C6W, C10W). RESULTS: The microCT
      demonstrated radiopacity at the distraction gap (DG) during C1W, which was filled
      with new bone at C6W and C10W. At D3D, collagen fibers were aligned along the
      axis of the distraction vector. At D6D, alkaline phosphatase-positive osteoblasts
      and intramembranous ossification was observed. Collagen bundles became thicker
      with new bony trabeculae at D10D. Type II collagen-immunopositive areas first
      appeared at C1W. At C3W, cartilage tissue and endochondral ossification were
      found. By C6W, the entire DG had been bridged by new bone. The C10W specimens
      showed mature lamellar bone. CONCLUSION: Mandibular DO produces bone through both
      intramembranous and endochondral ossification.

PMID- 18805718
TI  - A comparative evaluation of immediate dental implant with autogenous versus
      synthetic guided bone regeneration.
AB  - Immediate implant is a placement of the implant immediately into fresh extraction
      socket site after tooth extraction and is considered to be a predictable and
      acceptable procedure. The present work is designed to evaluate the periodontal
      condition after immediate implant placement and the success rate of implant with
      autogenous versus synthetic guided bone regeneration. Twenty adult male patients
      with an endodontic failure, tooth fracture decayed tooth (hopeless tooth) were
      included in this study. Patients were divided into 2 groups: One group (I)
      received immediate implants augmented with autogenous bone graft, and the other
      (group II) received immediate implants augmented with a synthetic bone graft. The
      results revealed that there was a significant difference between the groups for
      pocket depth and clinical attachment level. The difference between the groups was
      statistically highly significant only at 12 months (P < .01). In addition, there
      was statistically significant difference between the groups at 9 and 12 months (P
      < .001). Moreover, there was significant decrease of marginal bone loss in group
      I compared with group II (P < .01). In addition, there was statistically
      significant difference between the both groups at 9 and 12 months for bone
      density (P < .001). Moreover, there was significant decrease of marginal bone
      loss in group I compared with group II (P < .01). In conclusion, the immediate
      dental implant placement with autogenous bone graft showed a significant
      superiority to synthetic bone graft. In addition, the immediate placement-delayed
      loaded dental implant remains the procedure of choice for predictable achieving
      of osseointegration.

PMID- 18805719
TI  - Recurrent oral ulceration: aphthous-like ulcers in periodic syndromes.
AB  - Recurrent oral ulceration that clinically resembles recurrent aphthous stomatitis
      but presents atypically, including commencement after adolescence, with fever,
      with a strong family history, or failing to resolve with age, has been termed
      aphthous-like ulceration (ALU). It may be seen in some immunodeficiency states,
      chronic viral infections, rheumatologic disorders, skin diseases, and the
      periodic syndromes. The periodic syndromes, considered to be the prototypic
      autoinflammatory diseases, present with recurrent short attacks of myalgia,
      arthralgia, rashes, abdominal pain, lymphadenopathy, and fever. Several of the
      syndromes can result in amyloidosis. Genetic studies have enhanced the clinical
      characterization of these conditions and elucidation of their molecular
      etiopathogenesis. This paper describes 2 patients with periodic syndromes
      presenting with ALU and reviews the present understanding of the syndromes.

PMID- 18805720
TI  - Effect of hyperbaric oxygen on grafted and nongrafted calvarial critical-sized
      defects.
AB  - OBJECTIVES: This study was undertaken to evaluate the effect of hyperbaric oxygen
      (HBO) on the repair of critical-sized defects in the presence and absence of a
      nonvascularized autogenous bone graft. STUDY DESIGN: Ten New Zealand White
      rabbits were randomly divided into 2 groups of 5 animals each. Bilateral 15-mm
      calvarial defects were created in the parietal bones of each animal, resulting in
      20 critical-sized defects. Autogenous bone grafts (ABG) were allocated to the
      left or right defect of each animal. Group 1 received HBO treatment at 2.4 ATA
      100% oxygen for 90 minutes per day 5 days a week for 4 weeks. Group 2 served as a
      normobaric (NBO) control, breathing only room air. The animals in each group were
      humanely killed at 6 weeks. Calvaria were analyzed by micro-CT and
      histomorphometry. RESULTS: Micro-CT analysis indicated that as expected there was
      a higher bone mineral density (BMD) and bone mineral content (BMC) in ABG than
      unfilled defects (P < .05). However, there was a significant decline in the bone
      mineral content (BMC) of HBO-treated grafted defects compared to NBO-treated
      grafted defects (P < .05). Histologically complete bridging of the defect was
      observed in both NBO and HBO ABG grafted defects. Histomorphometic analysis
      showed that HBO treatment increased new bone and marrow, and reduced fibrous
      tissue in the defects (P < .01 for all). Examination of residual graft showed a
      near significant reduction in residual graft volume (11.2 +/- 4.7 versus 19.1 +/-
      7.7, HBO versus NBO P = .085) in the HBO group. The use of a graft increased new
      bone and marrow in the NBO group (P < .001 for both); however, in the HBO-treated
      animals the differences between grafted and ungrafted were not significant.
      CONCLUSION: HBO enhances bony healing in ungrafted rabbit calvarial critical
      sized defects and may increase the rate of residual graft resorption in
      autogenous bone-grafted defects.

PMID- 18805721
TI  - Different feed withdrawal times before slaughter influence caecal fermentation
      and faecal Salmonella shedding in pigs.
AB  - The effects of different pre-slaughter feed withdrawal times (FWT) on the
      gastrointestinal tract (GIT) weight and the gut environment of pigs and
      Salmonella shedding were investigated. Trial 1 evaluated the effects under
      experimental conditions (feed withdrawal for 18, 30 and 36 h) and trial 2 under
      commercial conditions (15 and 30 h). In trial 1, the GIT weight tended to
      decrease (P=0.07), the caecal pH increased (P<0.0001), short-chain fatty acids
      (SCFA) decreased (P<0.001) and percentage of branched-chain fatty acids (BCFA)
      increased as FWT increased. Similar results were observed in trial 2, but
      Enterobacteriaceae numbers and Salmonella positive pigs tended to increase
      whereas lactobacilli decreased (P<0.0005) as FWT increased. The increase in FWT
      involved changes in the gut microbial ecosystem that could be associated with the
      trend of increased caecal Enterobacteriaceae and Salmonella in faeces, and may
      represent a higher risk of carcass contamination in cases of laceration of
      viscera.

PMID- 18805722
TI  - In vivo delivery of human acid ceramidase via cord blood transplantation and
      direct injection of lentivirus as novel treatment approaches for Farber disease.
AB  - Farber disease is a rare lysosomal storage disorder (LSD) caused by a deficiency
      of acid ceramidase (AC) activity and subsequent accumulation of ceramide.
      Currently, there is no treatment for Farber disease beyond palliative care and
      most patients succumb to the disorder at a very young age. Previously, our group
      showed that gene therapy using oncoretroviral vectors (RV) could restore enzyme
      activity in Farber patient cells. The studies described here employ novel RV and
      lentiviral (LV) vectors that engineer co-expression of AC and a cell surface
      marking transgene product, human CD25 (huCD25). Transduction of Farber patient
      fibroblasts and B cells with these vectors resulted in overexpression of AC and
      led to a 90% and 50% reduction in the accumulation of ceramide, respectively.
      Vectors were also evaluated in human hematopoietic stem/progenitor cells (HSPCs)
      and by direct in vivo delivery in mouse models. In a xenotransplantation model
      using NOD/SCID mice, we found that transduced CD34(+) cells could repopulate
      irradiated recipient animals, as measured by CD25 expression. When virus was
      injected intravenously into mice, soluble CD25 was detected in the plasma and
      increased AC activity was present in the liver up to 14 weeks post-injection.
      These findings suggest that vector and transgene expression can persist long-term
      and offer the potential of a lasting cure. To our knowledge, this is the first
      report of in vivo testing of direct gene therapy strategies for Farber disease.

PMID- 18805723
TI  - Comments on Falgarone et al. editorial entitled "TNFalpha antagonists in
      rheumatoid arthritis patients seen in everyday practice".

PMID- 18805724
TI  - Leflunomide-induced toxic epidermal necrolysis in a patient with rheumatoid
      arthritis.
AB  - INTRODUCTION: Leflunomide is an immunomodulating agent with proven efficacy in
      rheumatoid arthritis. Although its overall safety profile is good, a few cases of
      toxic epidermal necrolysis have been reported. CASE REPORT: This 36-year-old
      woman had rheumatoid arthritis that proved refractory to sulfasalazine and
      methotrexate, which were used successively in combination with symptomatic drugs.
      Leflunomide was started. A maculopapular rash and a fever developed 2 weeks
      later. The skin lesions spread rapidly to most of the body, and ulcers of the
      ocular and oral mucosa appeared. Leflunomide was stopped. Cholestyramine washout
      and prednisolone (60 mg/day) were given. The skin lesions healed over the next
      month. Punctate keratitis with keratinization of the cornea led to complete loss
      of vision. DISCUSSION: The main adverse effects of leflunomide consist of
      diarrhea, nausea, liver enzyme elevation, hypertension, alopecia, and allergic
      skin reactions. A few cases of severe skin reactions such as toxic epidermal
      necrolysis have been reported. They require immediate discontinuation of the drug
      and a washout procedure to hasten drug elimination from the body. CONCLUSION:
      Close monitoring for severe skin reactions is in order when using leflunomide.

PMID- 18805725
TI  - Genetic analysis for five LRRK2 mutations in a Sardinian parkinsonian population:
      importance of G2019S and R1441C mutations in sporadic Parkinson's disease
      patients.
AB  - Mutations in the LRRK2 gene are the most common known cause of familial and
      sporadic Parkinson's disease (PD). Few studies performed to date to assess
      frequency of these mutations are actually only representative of specific areas.
      Here we study the frequency and clinical phenotype of LRRK2 G2019S, I2020T and
      R1441C/G/H mutations in 356 Sardinian patients with idiopathic PD and 208
      controls. Seventeen additional subjects, relatives of PD mutated probands, were
      enrolled. Eight patients were mutated in heterozygosis for LRRK2 gene (2.3%): six
      carried the G2019S (1.7%) and two the R1441C (0.6%) mutation. Three PD patients
      G2019S carriers (50%) were detected in two contiguous villages comprising 3921
      inhabitants while the other three (50%) were identified in the remaining
      population of 796,079 inhabitants. Only one mutated proband had a family history
      of PD. LRRK2 G2019S and R1441C mutations associated with PD were not an uncommon
      mutation in a Sardinian population, especially in sporadic PD patients. The
      detection of the G2019S variant in ten unaffected relatives confirms a reduced
      penetrance of the underlying mutation and might explain its prevalence among
      patients with sporadic PD. These findings may provide new insights into the
      importance of studies of frequency of LRKK2 mutations in PD patients originating
      from small ethnically homogeneous populations.

PMID- 18805726
TI  - Effects of lumbopelvic joint manipulation on quadriceps activation and strength
      in healthy individuals.
AB  - Lumbopelvic joint manipulation has been shown to increase quadriceps force output
      and activation, but the duration of effect is unknown. It is also unknown whether
      lower grade joint mobilisations may have a similar effect. Forty-two healthy
      volunteers (x+/-SD; age=28.3+/-7.3 yr; ht=172.8+/-9.8 cm; mass=76.6+/-21.7 kg)
      were randomly assigned to one of three groups (lumbopelvic joint manipulation, 1
      min lumbar passive range of motion (PROM), or prone extension on elbows for 3
      min). Quadriceps force and activation were measured using the burst
      superimposition technique during a seated isometric knee extension task before
      and at 0, 20, 40, and 60 min following intervention. Collectively, all groups
      demonstrated a significant decrease (p<0.001) in quadriceps force output without
      changes in activation (p>0.05) at all time intervals following intervention. The
      group that received a lumbopelvic joint manipulation demonstrated a significant
      increase in quadriceps force (3%) and activation (5%) (p<0.05) immediately
      following intervention, but this effect was not present after the 20 min
      interval. Since participants in this study were free of knee joint pathology, it
      is possible that they did not have the capacity to allow for large changes in
      quadriceps muscle activation to occur.

PMID- 18805727
TI  - Experimental pragmatics: a Gricean turn in the study of language.
AB  - Discerning the meaning of an utterance requires not only mastering grammar and
      knowing the meanings of words but also understanding the communicative (i.e.,
      pragmatic) features of language. Although it has been an ever present aspect of
      linguistic analyses and discussions, it is only over the last ten years or so
      that cognitive scientists have been investigating--in a concerted fashion--the
      pragmatic features of language experimentally. We begin by highlighting Paul
      Grice's contributions to ordinary language philosophy and show how it has led to
      this active area of experimental investigation. We then focus on two exemplary
      phenomena--'scalar inference' and 'reference resolution'--before considering
      other topics that fit into the paradigm known as 'experimental pragmatics'.

PMID- 18805728
TI  - The signing brain: the neurobiology of sign language.
AB  - Most of our knowledge about the neurobiological bases of language comes from
      studies of spoken languages. By studying signed languages, we can determine
      whether what we have learnt so far is characteristic of language per se or
      whether it is specific to languages that are spoken and heard. Overwhelmingly,
      lesion and neuroimaging studies indicate that the neural systems supporting
      signed and spoken language are very similar: both involve a predominantly left
      lateralised perisylvian network. Recent studies have also highlighted processing
      differences between languages in these different modalities. These studies
      provide rich insights into language and communication processes in deaf and
      hearing people.

PMID- 18805729
TI  - Down regulation and nuclear localization of human beta-defensin-1 in pleomorphic
      adenomas of salivary glands.
AB  - Although antimicrobial peptides (AMPs) appear to have diverse functional
      activities in innate immunity, a few reports suggest a potential role of human
      beta-defensin (hBD)-1 in tumor suppression. The aim of the present study was to
      compare the expression patterns of hBD-1, -2 and -3 in various features of human
      salivary gland tissues, such as healthy parenchyma, chronic sialadenitis and
      intraglandular pleomorphic adenomas, with their adjacent normal tissues. Twenty
      human salivary gland specimens (five healthy, five chronic sialadenitis, five
      pleomorphic adenomas and five adenoma adjacent normal tissues (AANTs)) were
      investigated for mRNA expression levels of hBD-1, -2 and -3 by quantitative real
      time RT-PCR. Additionally, immunohistochemistry for the hBD-1, -2 and -3 peptides
      was performed for analysis of localization. Considerably increased, 80-fold
      higher hBD-1 and increased hBD-3 mRNA expression levels compared to healthy
      salivary gland tissues were detected in chronic sialadenitis. In pleomorphic
      adenomas hBD-2 expression levels were lower, but hBD-1 expression levels were
      significant decreased (p=0.03) compared to healthy parenchyma. Interestingly, the
      AANTs showed a 48-fold higher expression of hBD-1 and increased hBD-3 expression
      compared to the healthy salivary gland. Immunohistochemistry of the tumors showed
      nuclear hBD-1 localization. For the first time, it was shown that hBD-1 gene
      expression is significantly decreased in pleomorphic adenomas, while
      simultaneously the protein is localized in the nucleus. Increased expression
      levels in glandular inflammation have been described previously albeit not in
      AANTs. These data support the hypothesis that hBD-1 might be a potential tumor
      suppressor also in benign salivary gland tumors in addition to other genetic
      alterations.

PMID- 18805730
TI  - Spectroscopic and theoretical study of 2-acetylphenyl-2-naphthoate.
AB  - Mid-, far-infrared and Raman vibrational spectra of 2-acetylphenyl-2-naphthoate
      have been measured at room and low temperatures. The molecule was also analyzed
      by means of ab initio calculations. The conformational space has been scanned
      using molecular dynamics and complemented with functional density calculations
      that optimize the geometry of the lowest energy conformers 2-acetylphenyl-2
      naphthoate as obtained in the simulations. The vibrational frequencies and the
      (1)H and (13)C NMR chemical shifts were assigned using functional density
      calculations. The theoretical chemical shift values were compared with the
      experimental ones. The molecular electrostatic potential maps were obtained and
      analyzed.

PMID- 18805731
TI  - Promoting interprofessional education in health sector within the European
      Interprofessional Education Network.
AB  - According to a common definition, interprofessional education (IPE) is described
      as "occasions when two or more professions learn from and about each other to
      improve collaboration and the quality of care". The Leonardo project under the
      name European Interprofessional Education Network (EIPEN) in health and social
      care, has been dealing with the challenges of interprofessional education. The
      EIPEN project tries to develop a transnational network of universities and
      employers in the six participating countries and at the same time to promote good
      practices in interprofessional learning and teaching in health and social care.
      IPE provides opportunities for students and practitioners to learn with, from and
      about each other during qualifying and post-qualifying training and in their
      practice. IPE in health and social care includes the education and training of
      practitioners in human and animal medicine, dentistry, nursing, physiotherapy,
      occupational therapy, pharmacy and all other health professions including public
      and environmental health and health promotion, and social work. The outcomes of
      the EIPEN Project will provide means, material and guidelines for the enhancement
      of professional education in the multi-disciplinary field of Health Informatics.
      The methodology on the development of the Greek Interprofessional Network was
      based on a series of workshops aiming to document the educational process in
      healthcare institutes and universities followed by the assessment of the needs
      for the development of an interprofessional environment. The outcomes will
      provide means, material and guidelines for the enhancement of professional
      education in the multi-disciplinary field of Health Informatics.

PMID- 18805732
TI  - A global approach to cancer-screening trials.

PMID- 18805733
TI  - A new HPV-DNA test for cervical-cancer screening in developing regions: a cross
      sectional study of clinical accuracy in rural China.
AB  - BACKGROUND: A new test (careHPV; QIAGEN, Gaithersburg, MD, USA) has been
      developed to detect 14 high-risk types of carcinogenic human papillomavirus (HPV)
      in about 2.5 h, to screen women in developing regions for cervical
      intraepithelial neoplasia (CIN). We did a cross-sectional study to assess the
      clinical accuracy of careHPV as a rapid screening test in two county hospitals in
      rural China. METHODS: From May 10 to June 15, 2007, the careHPV test was done
      locally by use of self-obtained vaginal and provider-obtained cervical specimens
      from a screening population-based set of 2530 women aged 30 to 54 years in Shanxi
      province, China. All women were assessed by visual inspection with acetic acid
      (VIA), Digene High-Risk HPV HC2 DNA Test (HC2), liquid-based cytology, and
      colposcopy with directed biopsy and endocervical curettage as necessary. In 2388
      women with complete data, 441 women with negative colposcopy, but unsatisfactory
      or abnormal cytology or who were positive on HC2 or the new careHPV test, were
      recalled for a second colposcopy, four-quadrant cervical biopsies, and
      endocervical curettage. An absence of independence between the tests was not
      adjusted for and the Bonferroni correction was used for multiple comparisons.
      FINDINGS: Complete data were available for 2388 (94.4%) women. 70 women had CIN2+
      (moderate or severe CIN or cancer), of whom 23 had CIN3+. By use of CIN2+ as the
      reference standard and area-under-the-curve analysis with a two-sided alpha error
      level of 0.0083, the sensitivities and specificities of the careHPV test for a
      cut-off ratio cut-point of 0.5 relative light units, were 90.0% (95% CI 83.0
      97.0) and 84.2% (82.7-85.7), respectively, on cervical specimens, and 81.4% (72.3
      90.5) and 82.4% (80.8-83.9), respectively, on vaginal specimens (areas under the
      curve not significantly different, p=0.0596), compared with 41.4% (29.9-53.0) and
      94.5% (93.6-95.4) for VIA (areas under the curve significantly different,
      p=0.0001 and p=0.0031, for cervical and vaginal-specimen comparisons for the
      careHPV test, respectively). The sensitivity and specificity of HC2 for cervical
      specimens were 97.1% (93.2-100) and 85.6% (84.2-87.1), respectively (areas under
      the curve not significantly different from the careHPV test on cervical
      specimens, p=0.0163). INTERPRETATION: The careHPV test is promising as a primary
      screening method for cervical-cancer prevention in low-resource regions.

PMID- 18805734
TI  - Plasmodium falciparum: a paradigm for alternative folate biosynthesis in diverse
      microorganisms?
AB  - Folates have a key role in metabolism, and the folate-dependent generation of DNA
      precursors in the form of deoxythymidine 5'-phosphate is particularly important
      for the replication of malaria parasites. Although Plasmodium falciparum can
      synthesize folate derivatives de novo, a long-standing mystery has been the
      apparent absence of a key enzyme, dihydroneopterin aldolase, in the classical
      folate biosynthetic pathway of this organism. The discovery that a different
      enzyme, pyruvoyltetrahydropterin synthase, can produce the necessary substrate
      for the subsequent step in folate synthesis raises the question of whether this
      solution is unique to P. falciparum. Bioinformatic analyses suggest otherwise and
      indicate that an alternative route to folate could be widespread among diverse
      microorganisms and could be a target for novel drugs.

PMID- 18805735
TI  - Malaria: some considerations regarding parasite productivity.
AB  - The complicated life cycle of Plasmodium is characterized by proliferative stages
      in each of its hosts--mosquito and vertebrate--that are interrupted by
      restrictive steps as it moves from one to the other. Productivity at each stage
      affects not only pathology but also the probability for successful transmission.
      This Opinion article briefly assesses what is known about productivity at each
      step and attempts, with limited success, to put each in the context of an entire
      cycle, sporozoite to sporozoite.

PMID- 18805736
TI  - Switching Plasmodium falciparum genes on and off for erythrocyte invasion.
AB  - Culture-adapted lines of the malaria parasite Plasmodium falciparum use
      alternative pathways for the invasion of erythrocytes. The expression of parasite
      ligands that are involved in the different pathways varies among parasite lines.
      Recently, several studies have attempted to characterize the use of different
      invasion pathways and the expression of specific invasion ligands in field
      isolates, opening the way to understand how invasion occurs in natural
      infections. In this review, these findings are discussed in the context of the
      most recent data on invasion by culture-adapted parasites to describe the current
      understanding of how wild parasites invade, how the variant expression of
      invasion ligands relates to switching between alternative invasion pathways and
      why so many different pathways are needed.

PMID- 18805738
TI  - Sudden unexpected death in epilepsy: current knowledge and future directions.
AB  - Although largely neglected in earlier literature, sudden unexpected death in
      epilepsy (SUDEP) is the most important epilepsy-related mode of death, and is the
      leading cause of death in people with chronic uncontrolled epilepsy. Research
      during the past two to three decades has shown that incidence varies
      substantially depending on the epilepsy population studied, ranging from 0.09 per
      1000 patient-years in newly diagnosed patients to 9 per 1000 patient-years in
      candidates for epilepsy surgery. Risk profiles have been delineated in case
      control studies. These and other studies indicate that SUDEP mainly occurs in the
      context of a generalised tonic-clonic seizure. However, it remains unclear why a
      seizure becomes fatal in a person that might have had many similar seizures in
      the past. Here, we review SUDEP rates, risk factors, triggers, and proposed
      mechanisms, and critically assess potential preventive strategies. Gaps in
      knowledge are discussed and ways forward are suggested.

PMID- 18805739
TI  - Minimal access surgery in the management of pediatric urolithiasis.
AB  - PURPOSE: In contrast to adult patients, a relatively large number of open
      surgical procedures are still needed in the treatment of urolithiasis in
      children. Since almost all open surgical techniques may be reproduced by minimal
      access surgery (MAS), there is a rationale to apply the latter in the management
      of pediatric urolithiasis. Our study aimed to assess the feasibility and outcome
      of MAS in the treatment of pediatric urinary calculi. MATERIALS AND METHODS: The
      charts of patients with urolithiasis submitted to MAS between 1994 and 2007 were
      retrospectively reviewed. The inclusion criteria were contraindication for and
      failure of lithotripsy or endourology techniques. Demographic data, lithiasis
      characterization (location, dimension, composition), predisposing factors
      (anatomic or metabolic) and surgical approach (technique and outcome) were
      evaluated. RESULTS: Fifteen consecutive patients (eight girls, seven boys) with a
      median age of 108 months (range: 10-297) were elected for MAS. Eleven (73%)
      children had associated urogenital malformations and three (20%) presented
      metabolic abnormalities. A total of 17 procedures were performed
      laparoscopically: three nephrolithotomies (one transperitoneal, two by
      retroperitoneoscopy), four pyelolithotomies (retro), three ureterolithotomies
      (trans) and seven cystolithotomies (suprapubic approach). Five patients underwent
      concomitant correction of urological anomalies (three calyceal diverticula, one
      obstructive megaureter, one ureteropelvic junction obstruction). Complete removal
      of calculi was accomplished in 14 (82%) procedures. There were two perioperative
      complications (one intraperitoneal vesical perforation and one perivesical
      urinoma). At a median follow up of 4 years (range: 1 month to 11 years), four
      patients have developed recurrence. CONCLUSIONS: Minimal access surgery is an
      effective and safe approach for urolithiasis in children who are not candidates
      for minimally invasive modalities. Individualized application of different
      techniques may solve virtually all cases. In selected cases, the role of MAS as
      first-choice therapy deserves consideration.

PMID- 18805740
TI  - Neuroendocrine carcinoma associated with X-linked hyper-immunoglobulin M
      syndrome: report of four cases and review of the literature.
AB  - X-linked hyper-immunoglobulin M syndrome (XHIGM) is a primary immunodeficiency
      disorder characterized by severe defects of both cellular and humoral immunity
      due to impaired expression of CD40 ligand on activated T lymphocytes. Patients
      with XHIGM usually present with a wide variety of infections caused by common and
      opportunistic pathogens including Pneumocystis jirovecii. In addition, subjects
      with XHIGM have an increased risk for hepatocellular and bile duct carcinomas,
      which are rarely observed in other primary immunodeficiencies. We present here
      clinical, immunological, and molecular findings of four patients with CD40 ligand
      deficiency associated with neuroendocrine carcinoma (NEC). NEC developed as a
      rapidly disseminated solid cancer leading to death in three patients. Data
      presented here and published previously suggest that CD40 ligand deficiency may
      predispose patients for the development of NEC. Histochemical findings suggested
      that CD56, in addition to cytokeratin and chromogranin A, may be a useful marker
      for early detection of NEC. We conclude that patients with XHIGM should be
      carefully followed to diagnose and treat NEC, a formidable neuroendocrine cancer.

PMID- 18805741
TI  - Distinct subsets of regulatory T cells during pregnancy: is the imbalance of
      these subsets involved in the pathogenesis of preeclampsia?
AB  - Regulatory T cells (CD4(+)CD25(+)FoxP3(+)-Treg cells) are important regulators of
      tolerance induction during pregnancy. We now found that the number of
      CD4(+)CD25(+)FoxP3(+)-Treg cells decreases during normal course of pregnancy and
      even more so in women affected by preeclampsia. The functional activity of these
      CD4(+)CD25(+)-Treg cells was significantly reduced in comparison to those of
      healthy pregnants. Further analysis revealed two Treg subsets that differed with
      regard to the FoxP3 and CD25 expression. The percentage of both,
      CD4(+)CD25(+)FoxP3(high+)-Treg and CD4(+)CD25(high+)FoxP3(+), was maximal in the
      first and second trimenon, but declined severely in the third trimenon. In
      preeclamptic women the population of CD4(+)CD25(high+)FoxP3(+)-Treg cells was
      particularly apparent, while the population of CD4(+)CD25(+)FoxP3(high+)-Treg
      cells was significantly decreased. We propose that CD4(+)CD25(+)FoxP3(high+)- and
      CD4(+)CD25(high+)FoxP3(+)-Treg cell populations represent distinct Treg cell
      subsets, and that disturbances in the balance of these two Treg cell subsets are
      associated with the presence of preeclampsia, but not HELLP-syndrome.

PMID- 18805742
TI  - Anti-shock garment in postpartum haemorrhage.
AB  - The non-pneumatic anti-shock garment (NASG) is a first-aid device that reverses
      hypovolaemic shock and decreases obstetric haemorrhage. It consists of
      articulated neoprene segments that close tightly with Velcro, shunting blood from
      the lower body to the core organs, elevating blood pressure and increasing
      preload and cardiac output. This chapter describes the controversial history of
      the predecessors of NASG, pneumatic anti-shock garments (PASGs), relates case
      studies of PASG for obstetric haemorrhage, compares pneumatic and non-pneumatic
      devices and posits why the NASG is more appropriate for low-resource settings.
      This chapter discusses the only evidence available about NASGs for obstetric
      haemorrhage - two pre-post pilot trials and three case series - and describes
      recently initiated randomized cluster trials in Africa. Instructions and an
      algorithm for ASGs in haemorrhage and shock management are included. Much remains
      unknown about the NASG, a promising intervention for obstetric haemorrhage
      management.

PMID- 18805743
TI  - Determination of baicalin in rat cerebrospinal fluid and blood using
      microdialysis coupled with ultra-performance liquid chromatography-tandem mass
      spectrometry.
AB  - An in vivo microdialysis sampling method coupled with ultra-performance liquid
      chromatography-tandem mass spectrometry (UPLC-MS/MS) was employed for continuous
      simultaneous monitoring of unbound baicalin in rat blood and brain. Microdialysis
      probes were inserted into the jugular vein and brain cerebrospinal fluid (CSF) of
      Sprague-Dawley rats then, following administration of baicalin at doses of
      24mg/kg via the candal vein, samples were collected every 20min and injected
      directly into the UPLC-MS/MS system. In vitro recoveries of the probes were
      19.26% and 18.38%, while in vivo recoveries of the probes were 15.0% and 17.52%
      for blood and brain, respectively. This improved method offers a rapid
      quantitative procedure for the determination of baicalin with a retention time of
      only 1.6min. The lower limit of quantification (LLOQ) and the lower limit of
      detection (LLOD) based on a signal-to-noise ratio of 5 were 2.37 and 0.1ng/ml for
      anticoagulant citrate dextrose (ACD) solution, and 1.185 and 0.3ng/ml for
      artificial cerebrospinal fluid (aCSF), respectively. The pharmacokinetics results
      indicated that baicalin could pass through the blood-brain barrier (BBB) and was
      detectable in brain dialysate. These in vivo microdialysis-based measurements
      provide a technique for simple sampling and rapid sensitive analysis of unbound
      baicalin in rat blood and CSF and for further application in pharmacokinetic
      studies.

PMID- 18805744
TI  - Combined therapy of selective embolization followed by surgery in a case of giant
      arteriovenous malformation in the buttock.

PMID- 18805745
TI  - Ear reconstruction following severe complications of otoplasty.
AB  - BACKGROUND: Correction of prominent ears is one of the most common operations
      performed in congenital deformity. Many appropriate corrective techniques have
      been described. While rare, severe complications destroying ear contours can
      occur and their correction should follow the established principles of ear
      reconstruction. METHODS: A retrospective review of the notes of all patients who
      presented to Clinique George Bizet (1981-2007) in Paris, for correction of
      complications after undergoing prominent ear surgery at another facility, was
      performed. Each patient's age, gender, diagnosis, number of previous operations
      and final outcome were noted as available. Patients were included in this study
      if they had undergone one or more operations for prominent ears, leading to
      severe destructive complications, prior to consultation with the senior author
      and then underwent surgical repair with either an auricular (conchal) cartilage
      graft or with autogenous costal cartilage. RESULTS: A total of 49 (25 female, 24
      male) patients met the inclusion criteria. The mean age at presentation was 23
      years (range of 10-59 years of age). The mean number of previous attempts to
      correct the ear deformity was 1.3 (1-12) times. Eight patients underwent
      reconstruction with a conchal cartilage graft and 41 with costal cartilage.
      CONCLUSIONS: While more minor contour deformities are correctable with a
      contralateral conchal cartilage graft, when more than a quarter of the ear or
      more than two planes of its complex folds are deformed, costal cartilage is
      recommended for surgical repair. The principles of ear reconstruction should be
      well understood prior to attempting a repair of severe complications after
      otoplasty.

PMID- 18805746
TI  - A solution to data-protection, confidentiality and image archiving.

PMID- 18805747
TI  - 'Functional and oncological outcomes after limb-salvage surgery for primary
      sarcomas of the upper limb' by Wright et al, J Plast Reconstr Aesthet Surg, 61,
      382-387.

PMID- 18805748
TI  - Neuroplasticity and critical thinking.

PMID- 18805749
TI  - Current trends in developing medical students' critical thinking abilities.
AB  - Health care is fallible and prone to diagnostic and management errors. The major
      categories of diagnostic errors include: (1) no-fault errors--the disease is
      present but not detected; (2) system errors--a diagnosis is delayed or missed
      because of the imperfection in the health care system; and (3) cognitive errors-
      a misdiagnosis from faulty data collection or interpretation, flawed reasoning,
      or incomplete knowledge. Approximately one third of patient problems are
      mismanaged because of diagnostic errors. Part of the solution lies in improving
      the diagnostic skills and critical thinking abilities of physicians as they
      progress through medical school and residency training. However, this task is
      challenging since both medical problem-solving and the learning environments are
      complex and not easily understood. There are many interacting variables including
      the motivation of the medical student (e.g. deep versus surface learning), the
      acquisition and evolution of declarative and conditional knowledge (e.g. reduced,
      dispersed, elaborated, scheme, and scripted), problem-solving strategies (e.g.
      procedural knowledge-guessing, hypothetical deductive, scheme inductive, and
      pattern recognition), curricular models (e.g. apprenticeship, discipline-based,
      body system-based, case-based, clinical presentation-based), teaching strategies
      (e.g. teaching general to specific or specific to general), the presented
      learning opportunities (PBL versus scheme inductive PBL), and the nature of the
      learning environment (e.g. modeling critical thinking and expert problem
      solving). This paper elaborates on how novices differ from experts and how
      novices can be educated in a manner that enhances their level of expertise and
      diagnostic abilities as they progress through several years of medical training.

PMID- 18805750
TI  - Role of case presentation for teaching and learning activities.
AB  - In most clinical teaching settings, case presentation is the most frequently used
      teaching and learning activity. From an educational viewpoint, the two important
      roles of case presentations are the presenter's reflective opportunity and the
      clinician educator's clues to diagnose the presenter. When a presenter prepares
      for a case presentation, he/she has to organize all the information collected
      from a patient. The presenter sometimes does not recall what to ask or to examine
      with relation to pertinent differential diagnoses while seeing a patient, and
      afterward he/she might note that more information should have been collected.
      He/she is able to note the processes by reflection-on-action and improve the
      processes the next time. Such a reflective process is the most important role of
      case conference for a presenter. When a clinician has a consultation with a
      patient, early problem representation determines the quality of differential
      diagnoses. Clinicians make a "big picture" while listening to the patient
      (sometimes only a glance is enough to diagnose a patient) as problem
      representation to narrow down clinical areas to ask questions. If the early
      problem representation is far from the optimal direction, the possibility of
      misdiagnosis will be higher. To correct the cognitive processes that lead to
      misdiagnosis, disclosure of uncertainty will be the key. If the teaching
      environment among residents or young clinicians is too competitive, some might
      feel reluctant to disclose incorrect reasoning processes to their peers. Or, if a
      clinician educator is too authoritative, students may hide key information from
      the educator. The educator should construct the best environment for students to
      be able to disclose such uncertainty. The main role of clinician educators is to
      facilitate and evaluate case presentations and to suggest points for improvement.
      Neher et al's "five microskills" are a typical example of these processes, after
      a short presentation of an outpatient case. Yet, for an inpatient or for formal
      discussion, a longer version presentation is used. To improve the clinical
      reasoning processes of the presenter, the short presentation has several
      advantages: (1) shortening the presentation requires abstraction of information,
      possibly leading to better problem representation; (2) it is time-efficient; and
      (3) it stimulates more informal interactions with the facilitator and the
      audience. In clinical settings, a presenter uses his/her time for the preparation
      of case presentations to reflect on the information he/she has collected. The
      facilitator should know how to improve case presentations to diagnose and improve
      the presenter. The advantages of the short presentation should be emphasized.

PMID- 18805751
TI  - Use of portfolios by medical students: significance of critical thinking.
AB  - Portfolios have been used in the medical curriculum to evaluate difficult-to
      assess areas such as students' attitudes, professionalism and teamwork. However,
      their use early in a problem-based learning (PBL) course to foster deep learning
      and enhance students' self-directed learning has not been adequately studied. The
      aims of this paper are to: (1) understand the uses of portfolios and the
      rationale for using reflection in the early years of a PBL curriculum; (2)
      discuss how to introduce portfolios and encourage students' critical thinking
      skills, not just reflection; and (3) provide students with tips that could
      enhance their skills in constructing good portfolios.

PMID- 18805752
TI  - Reflection and critical thinking of humanistic care in medical education.
AB  - The purpose of this paper is to stress the importance and learning issues of
      humanistic care in medical education. This article will elaborate on the
      following issues: (1) introduction; (2) reflection and critical thinking; (3)
      humanistic care; (4) core values and teaching strategies in medical education;
      and (5) learning of life cultivation. Focusing on a specific approach used in
      humanistic care, it does so for the purpose of allowing the health professional
      to understand and apply the concepts of humanistic value in their services.

PMID- 18805753
TI  - Community-oriented curriculum design for medical humanities.
AB  - Various recent surveys in Taiwan show physicians' decreasing satisfaction and
      increasing frustration with their working environment. Their major complaints are
      stress, long hours, salary, management's disrespect, and lack of trust from
      patients and society. To move towards restoration of social trust, this paper
      proposes incorporating the concept of "doctor as mediator in the changing
      relationship with patients" into the medical curriculum, as will be described in
      detail. This paper argues that structured community service for medical students
      facilitates self-learning, and will not only motivate them to develop good
      clinical and communication skills, but will also lead them to realize that the
      essence of medicine must be social trust. These effects have been seen after
      several years of an experimental curriculum involving more than 800 students. A
      program using methodology for community empowerment has been realized in a two
      stage curriculum design. Students' self-assessment of achievements in these
      courses included further improvement in communication skills, courage to express
      own position, appropriate planning in advance, management of human resources,
      ability to deal with limited space and time, and experience of a profoundly
      moving learning process. In conclusion, community-based curriculum designs that
      facilitate self-learning for medical students should be the key element of
      reformed humanities education in Taiwan medical schools. Moreover, medical
      humanities continues to be a key element contributing to ongoing intellectual
      movements in Taiwan for building civil society and rooting democracy in the
      community.

PMID- 18805754
TI  - Physician self-directed learning and education.
AB  - Physicians are expected to be life-long learners because updated and effective
      patient care should be provided while medical and clinical knowledge and skills
      and social requirements for patient care are rapidly changing. Also, qualified
      clinical competence needs long periods of training and each physician has to
      continually learn as long as he/she works as a professional. Self-directed
      learning is an important factor in adult learning. Medical students' readiness
      for self-directed learning is not high, and should be improved by medical school
      and postgraduate training curricula. Garrison proposed a comprehensive model of
      self-directed learning, and it has dimensions of motivation (entering and task),
      self-monitoring (responsibility), and self-management (responsibility). To teach
      individual self-directed learning competencies, the following are important: (1)
      situate learners to experience "real" problems; (2) encourage learners to reflect
      on their own performance; (3) create an educational atmosphere in clinical
      training situations. In 2005, a 2-year mandatory residency program was
      implemented in Japan, and fewer medical school graduates took residency programs
      in medical school hospitals and advanced specialty programs provided by medical
      school departments. Medical school departments provide traditional, but life-long
      clinical training opportunities. Under the new residency program, an additional
      postgraduate and continuing medical training system has to be built up to
      maintain and confirm a physician's competencies. If physicians do clinical work
      using a scholarly way of thinking with critical analysis of their own
      competencies and improvement by reflection, they will become an excellent life
      long learner.

PMID- 18805756
TI  - [A change of attitude in lipidology, achievement of target levels. What comes
      next?].
AB  - One of the greatest challenges of cardiovascular prevention is to minimize the
      risk of cardiovascular events through the achievement of target lipid levels. Its
      importance is suggested by the comprehensive meta-analyses of large scale
      clinical trials and the therapeutic guidelines determining everyday clinical
      practice. The attainment of target levels is often emphasized, nevertheless,
      there is a gap between theory and practice. The authors compare the goal
      attainment rate based on Hungarian medical literature and their own data, and
      analyze the possibilities of further improvement. The CEL Program evaluated the
      achievement rate of target total cholesterol levels in more than 10 000 patients
      of general practitioners in 2004, 2005 and 2006, and the ratio increased from 12%
      to 30% within 3 years. According to the results of the Hungarian REALITY study
      the rate of patients achieving the target total cholesterol levels was 21% in
      2004, and it increased to 27% during a 3-year period. To this very low improving
      rate also belongs the fact that in 2007, when only one fourth of patients were on
      target levels, 87% of general practitioners and 56% of specialists reconciled
      themselves to it and did not propose any modification in the therapy of patients
      not achieving the target levels. The surveys conducted at the department of
      internal medicine with cardiological profile of the county hospital in Gyula
      proved a considerable increase in the last 7 years in the administration of drugs
      improving the life expectancy of cardiovascular patients (aspirin, beta-blockers,
      ACE-inhibitors and statins) due to the widespread application of clinical
      guidelines and the special attention; nowadays the administration rate is above
      90% in all four groups. Nevertheless, the rate of patients achieving the LDL
      cholesterol goals was 37% in the high risk and 18% in the very high risk groups
      in December 2007 and January 2008. The fact that in the latter group only 21% of
      patients received combination therapy indicates that improving this ratio may be
      the next step. A greater emphasis should be placed on the achievement of target
      levels and regular revision of applied medical therapy, particularly in the high
      and very high risk patients as these groups can benefit the most from it.

PMID- 18805757
TI  - [Postoperative application of amphotericin B nasal spray in chronic
      rhinosinusitis with nasal polyposis. Can recidive polyposis be prevented?].
AB  - Chronic rhinosinusitis affects 1-4% of the adult population. The aetiology of
      this multifactorial, chronic disease, which leads to a significant impairment of
      the quality of life, often accompanied by nasal polyposis, is not fully
      understood. In the past decade it was presumed that the disease, which causes
      characteristic eosinophilic infiltration of the nasal mucosa, is triggered by an
      enhanced (but not classical allergic IgE type) immune response. AIM: If this
      supposition is correct, then it appears obvious that the administration of
      amphotericin B nasal spray in adequate concentration following endoscopic
      polypectomy should be advantageous for these patients, and might even reduce the
      number of recurrent cases. METHODS: To check on this assumption, the authors
      conducted a prospective randomized placebo-controlled trial involving 33
      patients, 30 of whom remained in the study throughout. Patients with nasal
      polyposis were operated on with an endoscopic technique between 1 November 2005
      and 1 October 2006; one group of them (group A, 14 randomly selected patients)
      was treated with a nasal spray containing 5 mg/ml amphotericin B, while the
      placebo group (group B, 16 randomly selected patients) received a nasal spray
      lacking amphotericin B. The results were evaluated with the aid of a modified
      Lund-Mackay CT score, the SNAQ-11 test (which evaluates changes in the symptoms),
      the life-quality test and endoscopy. The SPSS 14.0 for Windows program was
      utilized to process the data of examinations performed preoperatively and one
      year postoperatively. RESULTS: The CT scores of the group A patients exhibited
      wide scattering without signs of recovery one year after the operation. The CT
      scores of the group B patients indicated a slight improvement, though this did
      not prove significant in relation to group A. Both the SNAQ-11 test and the life
      quality test revealed a significant improvement in each group, but the degrees of
      change in these tests did not significantly differ between the two groups of
      patients. The endoscopic findings indicated a slight improvement to the advantage
      of the amphotericin B-treated group 12 months after the operation. CONCLUSION:
      These results lead to the conclusion that the administration of amphotericin B
      nasal spray to patients operated on for nasal polyposis does not give rise to a
      significant alteration in CT scores, clinical symptoms, or quality of life. The
      more favourable clinical aspects observed in the amphotericin B-treated group
      during the endoscopic follow-up did not correspond to an improvement in the
      symptoms. In connection with the conclusions drawn from this study the authors
      discuss the available data on the fungal theory. They critically analyse the
      contradictory observations of 7 recent clinical studies.

PMID- 18805758
TI  - [Selenium deficiency and infertility. Andrologic aspects].
AB  - Absolute selenium deficiency in human is very rare, although suboptimal daily
      selenium intake may lead to an unrecognized relative deficiency. Among the many
      consequences ascribed to decreased selenium level, the effect on male fertility
      is summarised by the authors. Implications from biochemical, animal experimental
      and human research are discussed.

PMID- 18805759
TI  - [Some recent ethical dilemmas in randomized controlled clinical trials].
AB  - Randomized controlled clinical trials (RCTs) are the golden standard of
      contemporary medical research. Just because they are ever more widespread, they
      stand at the focus of intense ethical debate. The debates have focused on the
      questions, how much the research participants can benefit from the research, and
      even if they can benefit from it, can a research ever be called therapeutic? Is
      not the notion of therapeutic research a misconception? Furthermore it has been
      debated when it is ethically acceptable to start an RCT, and is it acceptable to
      randomly assign research participants? When is it acceptable to use a placebo
      controlled trial? It has been debated, how to interpret the conception of
      "best... method" in the Declaration of Helsinki 2000. The article makes an
      attempt to survey some of the lessons of these debates.

PMID- 18805760
TI  - [Quality-of-life measures in pediatric cardiology].
AB  - The need of outcome measures from the patients' aspect emerges reasonably in the
      field of rapidly developing pediatric cardiac surgery and pediatric cardiology.
      The professional standards and the possibilities of applicability of quality of
      life measures are often unknown for medical doctors. This is particularly true in
      pediatrics due to the numerous difficulties of pediatric measures and--in
      consequence--to the lower number of correct investigations. AIM: To summarize the
      basic professional expectations and results of previous quality of life studies
      performed in pediatric cardiology from a clinical point of view. METHOD: Survey
      of the literature of quality of life measures performed on mixed or specified
      adult and child population with congenital heart disease with a presentation of
      the main results and the basic characteristics of methodology. CONCLUSION:
      According to previous results, quality of life measures have a role in pediatric
      cardiology. Adequate measures can improve the level of care.

PMID- 18805763
TI  - [New method for the treatment of atrial fibrillation: circumferential cryoballoon
      ablation of the pulmonary vein].
AB  - Atrial fibrillation is the most frequent arrhythmia with increasing prevalence.
      Given a limited success rate of drug therapy for atrial fibrillation,
      interventional treatment options have been developed during the last years.
      Catheter ablation of atrial fibrillation (until recently the mostly used energy
      source was radiofrequency energy) has been established as an important
      therapeutic alternative. Depending on interpersonal (both on patient and operator
      side) and technical variabilities using radiofrequency energy potentially life
      threatening complications such as pulmonary vein stenosis or atrio-esophageal
      fistulas may occur. Cryoenergy is a novel energy source for transcatheter
      ablation eliminating the arrhythmia substrate by freezing. The cornerstone of
      catheter ablation for atrial fibrillation is electrical isolation of the
      pulmonary veins. During cryoballoon ablation the targeted pulmonary vein
      transiently occluded by the inflated balloon catheter and using this method a
      circumferential lesion is created. The success rate of cryoballoon ablation is
      comparable with the radiofrequency ablation with increased safety. We performed
      the first cryoballoon ablations for patients with paroxysmal atrial fibrillation
      in Hungary. On this occasion we review the potential advantages of this technique
      which may serve as basis for its widespread use in the future.

PMID- 18805764
TI  - [Clinical application of nanoparticles, and their possible health risk].
AB  - Nanomaterials are getting rapidly developing practical applications, beside many
      others also in the clinical practice. Their beneficial attributes make the use of
      the nanostructures a large improvement in effective therapy as coating of
      implants, bone replacement materials, coating of active substances, nano-sized
      liposomes to achieve better pharmacologic qualities. Beside new beneficial
      chemical qualities originating from their size, due to the use of nanomaterials
      also adverse health effects may occur. Only in view of the possible effects on
      human health is the responsible use acceptable. The difference in qualities from
      other kinds of material can be explained by the nano-size. Investigations
      performed in the last decade have shown beside their local effect also systemic
      effects, like the rise of reactive oxygen species production, increase of
      platelet aggregation, which raises the cardiovascular risk. Due to the incomplete
      knowledge available now, it is not possible to assess the exact health risk;
      accordingly the application of nanomaterials in medical care has to be especially
      careful because of their possible partly unknown adverse health effects.

PMID- 18805765
TI  - [Polymorphisms of the Toll-like receptor 4 gene and their potential role in
      infectious diseases and chronic inflammatory disorders].
AB  - The Toll-like receptor 4 is a key mediator of the innate immune response. Besides
      its main ligand, the Gram-negative bacterial lipopolysaccharides, other molecules
      such as heat-shock protein 60, oxidized low density lipoprotein and fibronectin
      can also bind to the receptor. Activation of the Toll-like receptor induces the
      production of proinflammatory cytokines. There is increasing evidence showing
      that the Toll-like receptor 4 plays a role not only in the immune reaction
      against infectious agents but also in chronic non-infectious inflammatory
      diseases, such as atherosclerosis, diabetes mellitus and inflammatory bowel
      disease. This review briefly summarizes recent knowledge on the Toll-like
      receptor 4, its common co-segregation polymorphisms and the impact of these
      polymorphisms on various human diseases.

PMID- 18805766
TI  - [New results in the research of the biomechanics of the venous system].
AB  - The upright posture of man had been a major evolutional challenge. The mechanisms
      responsible for orthostatic tolerance mostly affect the venous system. In this
      paper, we discuss new results regarding the biomechanics of the venous system
      highlighting a rather neglected field, the biomechanical properties of the vein
      wall. These properties change according to localization of veins, age, gender and
      body mass. The anti-gravitational adaptation of veins is a complex process
      involving all three layers of the venous wall. Local myogenic and humoral
      mechanisms as well as systemic hormonal and nervous influences control the
      adaptive processes in the veins. Long term adaptation involves structural and
      functional remodeling of the venous wall. Disorders of the veins mostly cause
      pathological remodeling. Hemodynamic factors (pressure and flow) together with
      inflammatory processes may lead to pathological alterations, changing the
      biomechanical properties of the vein wall, which further contribute to the
      reservation and progression of venous dysfunction. Appropriate testing of venous
      function can reveal biomechanical disorders even in clinically asymptomatic
      patients. Thus, biomechanical investigation of veins not only helps to understand
      the underlying pathomechanism but it also can contribute to early diagnosis and
      follow-up of venous disorders. When recognized in time, pathological remodeling
      can be prevented or treated. In this way, the incidence of venous disorder could
      be cut back reducing both human suffering and material loss.

PMID- 18805767
TI  - [Laszlo Blaskovics (1869-1938)].

PMID- 18805768
TI  - [Physicians' portraits on medals by Miklos Borsos].

PMID- 18805771
TI  - [Combined antihypertensive and antilipemic therapy as one of the pillars in the
      poly-pharmacologic preventive strategy for patients with high cardiovascular
      risk].
AB  - Hypertension is a highly prevalent disease and a strong risk factor for
      cardiovascular disease in industrialized countries in Europe and North America.
      About 40-50% of hypertensive patients have some other cardiovascular risk factors
      as smoking, dyslipidemia, glucose intolerance, metabolic syndrome and diabetes.
      The realization of optimal therapy of these patients is a difficult task, and
      reaching target blood pressure values is almost impossible by monotherapy. It was
      realized that the simultaneous normalization of blood pressure and that of
      abnormal lipid profile with 2-3 or more drugs have great importance for
      preventing atherosclerotic complications.We started an open-formed study with
      about 1000 hypertensive patients complicated with dyslipidemia, visceral obesity,
      metabolic syndrome and diabetes type 2. The base of our therapeutic strategy was
      a typical poly-pharmacologic treatment with ACE inhibitor (lisinopril), calcium
      antagonist (amlodipine), statin (atorvastatin) and antiplatelet therapy (if it
      was necessary).

PMID- 18805772
TI  - [Haplogroup analysis of vitamin-K epoxide reductase (VKORC1) gene: novel element
      in the optimization of anticoagulant therapy].
AB  - Warfarin and acenocoumarols are the most commonly prescribed anticoagulants that
      is difficult to use because of the wide intra- and interpatient variation in the
      dose requirements, the narrow therapeutic range and the risk of serious bleeding.
      Vitamin K epoxide reductase (VKORC1) is the site of inhibition by coumarins.
      Mutations in the VKORC1 gene affect the sensitivity of the epoxy reductase enzyme
      for warfarin. The three main haplotypes of VKORC1 gene, *2, *3, *4, explain most
      of the genetic variability in warfarin dose among Caucasians. In the current
      paper we focus on this subject in view of our experience gained during molecular
      genetic tests for the main VKORC1 haplotypes in Hungarian patients with
      anticoagulant therapy and unusual clinical response. A total of 28 selected cases
      were characterized for VKORC1 G-1639A, G9041A and C6009T alleles. Genotyping has
      been carried out by molecular biology techniques, including PCR-RFLP assay and
      direct sequencing. In patients undergoing anticoagulant therapy we could identify
      VKORC1 *1*2, *2*2, *2*3, *1*4, *2*4 and *3*4 haplotypes. Patients with A
      haplotype group (14% of the studied patients) require much lower warfarin doses
      than other patients (2.7+/-0.2 mg/day). In our patients we found some with B
      haplotype group (25%) who require high warfarin dose (6.2+/-0.3 mg/day). There
      were also subjects bearing the A/B haplotype group (61%) with intermediate
      warfarin dose (4.9+/-0.2 mg/day), estimated by the haplotype analyses of the
      VKORC1 gene. Results presented here underline the need of VKORC1 haplotyping in
      anticoagulated patients with unusual clinical anticoagulant response, and the
      examination can have further therapeutic consequences.

PMID- 18805773
TI  - [Diclofenac/orphenadrine as a combined analgetic in post-operative relief of
      pain].
AB  - The authors compared the potency, safety and tolerability of combined infusion
      containing non-steroid anti-inflammation diclofenac and central muscle relaxant
      orphenadrine, and those of tramadol HCl, during postoperative pain relief after
      low and middle category operations. The test was an open, group- and self
      controlled, prospective, randomised, IV. phase clinical test. The involved 60
      patients were given analgesics for 74 days. The patients were divided into three
      groups: those in group A ( n = 19) were given diclofenac-orphenadrine, those in
      group B ( n = 30) tramadol, while those in group C ( n = 11) both diclofenac
      orphenadrine and tramadol. The received data were statistically analysed. For the
      assessment of the analgesics' potency, the visual analogue scale (VAS) was used.
      As a result of the treatment, VAS values in all three groups decreased
      significantly ( p < 0.001) both in inactive (-2.5, -3.7, -3.0) and active (-3.0, 
      3.8, -3.4) state, so pain relief was successful. This was also supported by the
      analysis of cardiovascular parameters. At the end of the treatment, both the
      patients and the physicians considered potency significantly ( p < 0.05 and p <
      0.01) better in group A which received only diclofenac-orphenadrine infusion.
      Analysing the quantity of used analgesics, the quantity of tramadol administered
      as a complement in group C was significantly smaller than in group B receiving
      only tramadol ( B: 87.5 mg, C: 61.5 mg, p < 0.01), which means that diclofenac
      orphenadrine infusion increased the analgesic effect of tramadol. Laboratory
      parameters measured at the beginning and at the end of treatment were inside
      physiological limits, as side effects nausea and vomiting were observed in 3
      cases. Based on all this, diclofenac-orphenadrine infusion is considered an
      effective and safe analgesic which is easy to administer and to combine in pain
      relief after small and middle category operations.

PMID- 18805774
TI  - [Efficacy of the emergency unit's filter function in patients with psychiatric
      symptoms].
AB  - The fundamental functions of the recently established emergency units/departments
      include the initial assessment, triage, commencement of treatment and referral
      for admission to the hospital. AIM: The aim of the study was to analyze
      psychiatric cases assessed at the department of emergency with particular
      reference to misdiagnoses and the reasons why emergency physicians failed to
      reach correct diagnoses. METHOD: This is a chart review of patients with
      psychiatric diagnoses evaluated at the Department of Emergency, Mohacs City
      Hospital during 2006. These patients were followed through the electronic
      database of the hospital and their socio-demographic and clinical characteristics
      were analyzed. RESULTS: Of the 596 patients who were considered primarily
      psychiatric cases during 2006, 289 (49%) were admitted to the psychiatric ward,
      182 (30%) were referred to outpatient treatment, and 125 (21%) were misdiagnosed
      and proved to be non-psychiatric emergencies and eventually ended up in other
      wards (75 patients in internal medicine, 20 in neurology, 12 in intensive care,
      and 18 in other units). CONCLUSION: Overall, the diagnostic and triage functions
      of the department of emergency were satisfactory in psychiatric cases. Medical
      emergencies that were frequently mistaken for psychiatric cases (e.g. atypical
      pneumonia, sensory aphasia) deserve particular attention. The authors emphasize
      the importance of the close collaboration of different medical areas involved in
      emergency assessment and treatment.

PMID- 18805775
TI  - [Intracardiac echocardiography-guided cardiac tumor mass biopsy].
AB  - Primary cardiac tumors are rare and often occur without major symptoms. The
      appropriate therapy for cardiac tumors without metastasis is surgical resection
      and chemotherapy. However, for certain patients, when the tumor cannot be safely
      removed, biopsy is recommended since it allows histology examination and further
      therapeutical considerations. The aim of our case presentation is to describe the
      case of a 56-year-old woman, in whom cardiac tumor-mass was revealed because of
      recurrent pericardial fluids. The mass appeared to be non-resectable, therefore
      biopsy with an eventual histological examination was planned. Intracardiac
      echocardiography guided percutaneous biopsy was performed. Intracardiac
      ultrasound ensured accurate localization of the tumor, the catheter-based
      grasping device and the excision could be instantly monitored. This case
      demonstrates that an intracardiac ultrasound-guided tumor mass biopsy is a
      feasible method, which increases accuracy and ensures safety.

PMID- 18805779
TI  - [We don't learn from praise . . . --Interview with Dr. Sandor Balogh].

PMID- 18805780
TI  - Employees' job satisfaction after the introduction of a total smoke-ban in bars
      and restaurants in Norway.
AB  - The aim of the study was to investigate possible effects of a total smoke-ban in
      Norwegian bars and restaurants (introduced on June 1st 2004) on employees' job
      satisfaction. A national representative sample was randomly selected from the
      public registry of all companies in the hospitality business. A baseline survey
      was conducted in May 2004, follow-up measurements were performed in
      September/October 2004 and May 2005. Altogether, 1525 employees agreed to
      participate in the baseline survey. Among respondents at baseline, 894 (59.4%)
      remained in the sample at the first follow-up and 758 (49.7%) at the second
      follow-up. Analysis of variance for repeated measures revealed a significant
      three-way interaction between personal smoking behaviour, attitudes towards the
      ban before it was enacted and time from baseline to the second follow-up. A small
      decline in job satisfaction was found between baseline and the first follow-up
      among employees who were daily smokers and had a negative attitude towards the
      ban. There was, however, an increase in job satisfaction between the first and
      second follow-up among the others (non-smokers and smokers with a positive
      attitude towards the ban). While job satisfaction was higher among smokers with
      negative attitudes towards the ban than among other employees before the ban
      entered into force, the opposite was the case one year later. The work
      environments in bars and restaurants seem to have changed towards being more
      satisfactory for non-smokers and smokers with positive attitudes towards the ban
      before it was enacted. In contrast, a small but persisting worsening of job
      satisfaction was found among employees that were daily smokers and had a negative
      attitude towards the ban.

PMID- 18805782
TI  - Endothelial CD81 is a marker of early human atherosclerotic plaques and
      facilitates monocyte adhesion.
AB  - AIMS: In a recent report, we established at the genome-wide level those genes
      that are specifically upregulated in the endothelium of atherosclerotic plaques
      in human arteries. As the transcriptome data revealed that mRNA for the
      tetraspanin family member CD81 is significantly and specifically upregulated in
      the endothelium overlying early atheroma, we set out to validate these results on
      the protein level, and investigate the functional consequences of CD81
      upregulation. METHODS AND RESULTS: Immunohistochemical analysis in an independent
      set of donor arteries verified in the endothelium of early human atherosclerotic
      lesions the enhanced expression of CD81, which appears oxidative stress
      dependent. Using lentiviral overexpression and silencing in human umbilical
      endothelial cells, we established in an in vitro flow adhesion assay that
      elevated endothelial CD81 is associated with increased monocyte adhesion to non
      activated CD81-transduced endothelial cells, approaching the levels normally only
      attained after tumour necrosis factor alpha stimulation. The CD81 effect was
      dependent on both intracellular adhesion molecule 1 (ICAM-1) and vascular cell
      adhesion molecule 1 (VCAM-1), as it was abolished in the presence of a mixture of
      anti-ICAM-1 and anti-VCAM-1 antibodies. Flow cytometry revealed that increased
      CD81 levels did not increase total ICAM-1 and VCAM-1 surface expression. Instead,
      it concentrated the available adhesion molecules into membrane clusters, as
      indicated by confocal and electron microscopy. CD81 also colocalized with ICAM-1
      and VCAM-1 in the adhesion rings around bound monocytes. CONCLUSION: Endothelial
      CD81 upregulated in early human atheroma has the potential to play a crucial role
      in the initial stages of atherosclerotic plaque formation by increasing monocyte
      adhesion prior to the full-blown inflammatory response.

PMID- 18805781
TI  - Over-expression of a modified bifunctional apoptosis regulator protects against
      cardiac injury and doxorubicin-induced cardiotoxicity in transgenic mice.
AB  - AIMS: Bifunctional apoptosis regulator (BAR) is an endoplasmic reticulum protein
      that interacts with both the extrinsic and intrinsic apoptosis pathways. We
      hypothesize that over-expression of BAR Delta RING prevents apoptosis and injury
      following ischaemia/reperfusion (I/R) and attenuates doxorubicin (DOX)-induced
      cardiotoxicity. METHODS AND RESULTS: We generated a line of transgenic mice that
      carried a human BAR Delta RING transgene under the control of the mouse alpha
      myosin heavy chain promoter. The RING domain, which binds ubiquitin conjugating
      enzymes, was deleted to prevent auto-ubiquitination of BAR and allow accumulation
      of the BAR protein, which binds apoptosis-regulating proteins. High levels of
      human BAR Delta RING transcripts and 42 KDa BAR Delta RING protein were expressed
      in the hearts of transgenic mice. When excised hearts were reperfused ex vivo for
      45 min as Langendorff preparations after 45 min of global ischaemia, the
      functional recovery of the hearts, expressed as left ventricular developed
      pressure x heart rate, was 23 +/- 1.7% in the non-transgenic hearts compared with
      51.5 +/- 4.3% in the transgenic hearts (P < 0.05). For in vivo studies, mice were
      subjected to 50 min of ligation of the left descending anterior coronary artery
      followed by 4 h of reperfusion. The infarct sizes following I/R injury, expressed
      as the percentage of the area at risk, were significantly smaller in the
      transgenic mice than in the non-transgenic mice (29 +/- 4 vs. 55 +/- 4%, P <
      0.05). In hearts of mice subjected to cardiac I/R injury, BAR transgenic hearts
      had significantly fewer in situ oligo-ligation-positive cardiac cells (5.0 +/-
      0.4 vs. 13.4 +/- 0.5%, P < 0.05). Over-expression of BAR Delta RING also
      significantly attenuated DOX-induced cardiac dysfunction and apoptosis.
      CONCLUSION: Our results demonstrate that over-expression of BAR Delta RING
      renders the heart more resistant to I/R injury and DOX-induced cardiotoxicity,
      and this protection correlates with reduced cardiomyocyte apoptosis.

PMID- 18805783
TI  - Larger dispersion of INa in female dog ventricle as a mechanism for gender
      specific incidence of cardiac arrhythmias.
AB  - AIMS: Women have a higher incidence of long QT-related arrhythmias, whereas men
      exhibit a higher incidence of Brugada syndrome (BrS). The cardiac sodium current
      (I(Na)) is associated with arrhythmias in BrS and long QT-syndrome (LQTS) and
      conduction disease. Although a great deal of work has been performed to explain
      how heterogeneous distribution of repolarizing currents triggers arrhythmias, the
      transmural distribution of I(Na) within the cardiac ventricle and its
      contribution to generate the arrhythmogenic substrate remain unknown. We
      undertook to determine whether I(Na) was heterogeneously distributed within the
      ventricular wall of canine heart, an animal model close to humans. METHODS AND
      RESULTS: Using patch-clamp and molecular biology techniques, we tested whether
      gender differences exist in the ventricular distribution and amplitude of I(Na)
      in the canine heart model. Our results show that the I(Na) amplitude is smaller
      in the female epicardial and endocardial layers of the left ventricle, but
      similar to male in the mid-myocardium. Exposure of female cardiomyocytes to
      testosterone increased the amplitude of I(Na) to levels similar to male in
      epicardium, but had no effects in mid-myocardial and endocardial cells. Castrated
      male dogs displayed I(Na) amplitudes similar to what was found in female hearts.
      CONCLUSION: The larger dispersion of I(Na) amplitude within the female cardiac
      ventricle may contribute to the higher risk of arrhythmias in females.
      Testosterone modulates this dispersion. By decreasing the transmural dispersion
      of I(Na), testosterone may exert a protective effect against LQTS-related
      arrhythmias in males.

PMID- 18805784
TI  - Pharmacological activation of the prostaglandin E2 receptor EP4 improves cardiac
      function after myocardial ischaemia/reperfusion injury.
AB  - AIMS: Increased expression of several subtypes of prostaglandin E(2) receptors
      (EP1-4) has recently been described in clinical and experimental myocardial
      ischaemia/reperfusion (I/R) injury. However, their pathophysiological
      significance in I/R remains obscure. Thus, we determined whether the activation
      of the prostanoid receptor, EP4, suppresses myocardial I/R injury. METHODS AND
      RESULTS: To analyse the role of EP4, we administered an EP4 selective agonist
      (EP4RAG, 1 or 3 mg/kg) or vehicle to rats with myocardial I/R injury. After 7
      days of reperfusion, I/R rats exhibited left ventricular (LV) dilatation and
      contractile dysfunction with myocyte hypertrophy and interstitial fibrosis.
      EP4RAG significantly reduced infarction area/ischaemic myocardium (72.4 +/- 0.7
      vs. 23.3 +/- 0.6%; P < 0.05) and improved LV contraction and dilatation compared
      with that of the vehicle. EP4RAG also attenuated the recruitment of inflammatory
      cells, especially macrophages, and interstitial fibrosis in hearts. Monocyte
      chemoattractant protein (MCP)-1 and other cytokines were increased in both non
      ischaemic (area not at risk, ANAR) and ischaemic (area at risk, AAR) myocardium;
      however, western blot analysis and RNase protection assay showed that EP4RAG
      suppressed these changes. Gelatin zymography revealed EP4RAG significantly
      reduced matrix metalloproteinase-2 and -9 activities in both ANAR and AAR.
      Chemoattractant assay demonstrated that EP4RAG suppressed the migration of
      cytokine-stimulated macrophages and decreased the level of MCP-1 production in
      the supernatant (587.3 +/- 55.3 vs. 171.5 +/- 47.5 pg/mL; P < 0.05). CONCLUSION:
      The data suggest that the EP4 agonist is effective for attenuation of I/R injury
      by suppressing MCP-1 and the infiltration of inflammatory cells, especially
      macrophages.

PMID- 18805785
TI  - The TREX1 double-stranded DNA degradation activity is defective in dominant
      mutations associated with autoimmune disease.
AB  - Mutations in TREX1 have been linked to a spectrum of human autoimmune diseases
      including Aicardi-Goutieres syndrome (AGS), familial chilblain lupus (FCL),
      systemic lupus erythematosus, and retinal vasculopathy and cerebral
      leukodystrophy. A common feature in these conditions is the frequent detection of
      antibodies to double-stranded DNA (dsDNA). TREX1 participates in a cell death
      process implicating this major 3' --> 5' exonuclease in genomic DNA degradation
      to minimize potential immune activation by persistent self DNA. The TREX1 D200N
      and D18N dominant heterozygous mutations were identified in AGS and FCL,
      respectively. TREX1 enzymes containing the D200N and D18N mutations were compared
      using nicked dsDNA and single-stranded DNA (ssDNA) degradation assays. The
      TREX1WT/D200N and TREX1WT/D18N heterodimers are completely deficient at degrading
      dsDNA and degrade ssDNA at an expected approximately 2-fold lower rate than
      TREX1WT enzyme. Further, the D200N- and D18N-containing TREX1 homo- and
      heterodimers inhibit the dsDNA degradation activity of TREX1WT enzyme, providing
      a likely explanation for the dominant phenotype of these TREX1 mutant alleles in
      AGS and FCL. By comparison, the TREX1 R114H homozygous mutation causes AGS and is
      found as a heterozygous mutation in systemic lupus erythematosus. The
      TREX1R114H/R114H homodimer has dysfunctional dsDNA and ssDNA degradation
      activities and does not detectibly inhibit the TREX1WT enzyme, whereas the
      TREX1WT/R114H heterodimer has a functional dsDNA degradation activity, supporting
      the recessive genetics of TREX1 R114H in AGS. The dysfunctional dsDNA degradation
      activities of these disease-related TREX1 mutants could account for persistent
      dsDNA from dying cells leading to an aberrant immune response in these clinically
      related disorders.

PMID- 18805786
TI  - The hepatitis B virus precore protein is retrotransported from endoplasmic
      reticulum (ER) to cytosol through the ER-associated degradation pathway.
AB  - The hepatitis B virus precore protein is closely related to the nucleocapsid core
      protein but is processed distinctly in the cell and plays a different role in the
      viral cycle. Precore is addressed to the endoplasmic reticulum (ER) through a
      signal peptide, and the form present in the ER is the P22 protein. P22 is then
      cleaved in its C-terminal part to be secreted as HBe antigen. In addition, a
      cytosolic form of 22 kDa less characterized has been observed. Precore gene was
      shown to be implicated in viral persistence, but until now, the actual protein
      species involved has not been determined. Our work focuses on the cytosolic form
      of precore. Using human cells expressing precore and a convenient fractionation
      assay, we demonstrated that the cytosolic form is identical to the ER form and
      retrotransported in the cytoplasm through the ER-associated degradation pathway.
      This cellular machinery translocates misfolded proteins to the cytoplasm, where
      they are ubiquitinated on lysine residues and degraded by proteasome. We showed
      that precore escapes proteasome due to its low lysine content and accumulates in
      the cytosol. The role of this retrotransport was investigated. In the presence of
      precore, we found a specific redistribution of the Grp78/BiP chaperone protein to
      cytosol and demonstrated a specific interaction between precore and Grp78/BiP.
      Altogether, these data support the idea that the hepatitis B virus develops a
      strategy to take advantage of the ER-associated degradation pathway, allowing
      distinct subcellular localization and probably distinct roles for the viral
      precore protein.

PMID- 18805787
TI  - Sphingosine 1-phosphate modulates spinal nociceptive processing.
AB  - Sphingosine 1-Phosphate (S1P) modulates various cellular functions such as
      apoptosis, cell differentiation, and migration. Although S1P is an abundant
      signaling molecule in the central nervous system, very little is known about its
      influence on neuronal functions. We found that S1P concentrations were
      selectively decreased in the cerebrospinal fluid of adult rats in an acute and an
      inflammatory pain model. Pharmacological inhibition of sphingosine kinases (SPHK)
      decreased basal pain thresholds and SphK2 knock-out mice, but not SphK1 knock-out
      mice, had a significant decrease in withdrawal latency. Intrathecal application
      of S1P or sphinganine 1-phosphate (dihydro-S1P) reduced the pain-related
      (nociceptive) behavior in the formalin assay. S1P and dihydro-S1P inhibited
      cyclic AMP (cAMP) synthesis, a key second messenger of spinal nociceptive
      processing, in spinal cord neurons. By combining fluorescence resonance energy
      transfer (FRET)-based cAMP measurements with Multi Epitope Ligand Cartography
      (MELC), we showed that S1P decreased cAMP synthesis in excitatory dorsal horn
      neurons. Accordingly, intrathecal application of dihydro-S1P abolished the cAMP
      dependent phosphorylation of NMDA receptors in the outer laminae of the spinal
      cord. Taken together, the data show that S1P modulates spinal nociceptive
      processing through inhibition of neuronal cAMP synthesis.

PMID- 18805788
TI  - A combination of HNF-4 and Foxo1 is required for reciprocal transcriptional
      regulation of glucokinase and glucose-6-phosphatase genes in response to fasting
      and feeding.
AB  - Glucokinase (GK) and glucose-6-phosphatase (G6Pase) regulate rate-limiting
      reactions in the physiologically opposed metabolic cascades, glycolysis and
      gluconeogenesis, respectively. Expression of these genes is conversely regulated
      in the liver in response to fasting and feeding. We explored the mechanism of
      transcriptional regulation of these genes by nutritional condition and found that
      reciprocal function of HNF-4 and Foxo1 plays an important role in this process.
      In the GK gene regulation, Foxo1 represses HNF-4-potentiated transcription of the
      gene, whereas it synergizes with HNF-4 in activating the G6Pase gene
      transcription. These opposite actions of Foxo1 concomitantly take place in the
      cells under no insulin stimulus, and such gene-specific action was promoter
      context-dependent. Interestingly, HNF-4-binding elements (HBEs) in the GK and
      G6Pase promoters were required both for the insulin-stimulated GK gene activation
      and insulin-mediated G6Pase gene repression. Indeed, mouse in vivo imaging showed
      that mutating the HBEs in the GK and G6Pase promoters significantly impaired
      their reactivity to the nutritional states, even in the presence of intact Foxo1
      binding sites (insulin response sequences). Thus, in the physiological response
      of the GK and G6Pase genes to fasting/feeding conditions, Foxo1 distinctly
      decodes the promoter context of these genes and differently modulates the
      function of HBE, which then leads to opposite outcomes of gene transcription.

PMID- 18805789
TI  - Coordinating the initial steps of base excision repair. Apurinic/apyrimidinic
      endonuclease 1 actively stimulates thymine DNA glycosylase by disrupting the
      product complex.
AB  - DNA glycosylases initiate base excision repair by removing damaged or mismatched
      bases, producing apurinic/apyrimidinic (AP) DNA. For many glycosylases, the AP
      DNA remains tightly bound, impeding enzymatic turnover. A prominent example is
      thymine DNA glycosylase (TDG), which removes T from G.T mispairs and recognizes
      other lesions, with specificity for damage at CpG dinucleotides. TDG turnover is
      very slow; its activity appears to reach a plateau as the [product]/[enzyme]
      ratio approaches unity. The follow-on base excision repair enzyme, AP
      endonuclease 1 (APE1), stimulates the turnover of TDG and other glycosylases,
      involving a mechanism that remains largely unknown. We examined the catalytic
      activity of human TDG (hTDG), alone and with human APE1 (hAPE1), using pre-steady
      state kinetics and a coupled-enzyme (hTDG-hAPE1) fluorescence assay. hTDG
      turnover is exceedingly slow for G.T (k(cat)=0.00034 min(-1)) and G.U
      (k(cat)=0.005 min(-1)) substrates, much slower than k(max) from single turnover
      experiments, confirming that AP-DNA release is rate-limiting. We find
      unexpectedly large differences in k(cat) for G.T, G.U, and G.FU substrates,
      indicating the excised base remains trapped in the product complex by AP-DNA.
      hAPE1 increases hTDG turnover by 42- and 26-fold for G.T and G.U substrates, the
      first quantitative measure of the effect of hAPE1. hAPE1 stimulates hTDG by
      disrupting the product complex rather than merely depleting (endonucleolytically)
      the AP-DNA. The enhancement is greater for hTDG catalytic core (residues 111-308
      of 410), indicating the N- and C-terminal domains are dispensable for stimulatory
      interactions with hAPE1. Potential mechanisms for hAPE1 disruption of the of hTDG
      product complex are discussed.

PMID- 18805790
TI  - Crystal structure of human type III collagen Gly991-Gly1032 cystine knot
      containing peptide shows both 7/2 and 10/3 triple helical symmetries.
AB  - Type III collagen is a critical collagen that comprises extensible connective
      tissue such as skin, lung, and the vascular system. Mutations in the type III
      collagen gene, COL3A1, are associated with the most severe forms of Ehlers-Danlos
      syndrome. A characteristic feature of type III collagen is the presence of a
      stabilizing C-terminal cystine knot. Crystal structures of collagen triple
      helices reported so far contain artificial sequences like (Gly-Pro-Pro)(n) or
      (Gly-Pro-Hyp)(n). To gain insight into the structural properties exhibited by the
      natural type III collagen triple helix, we synthesized, crystallized, and
      determined the structure of a 12-triplet repeating peptide containing the natural
      type III collagen sequence from residues 991 to 1032 including the C-terminal
      cystine knot region, to 2.3A resolution. This represents the longest collagen
      triple helical structure determined to date with a native sequence. Strikingly,
      the Gly(991)-Gly(1032) structure reveals that the central non-imino acid
      containing region adopts 10/3 superhelical properties, whereas the imino acid
      rich N- and C-terminal regions adhere to a 7/2 superhelical conformation. The
      structure is consistent with two models for the cystine knot; however, the poor
      density for the majority of this region suggests that multiple conformations may
      be adopted. The structure shows that the multiple non-imino acids make several
      types of direct intrahelical as well as interhelical contacts. The looser
      superhelical structure of the non-imino acid region of collagen triple helices
      combined with the extra contacts afforded by ionic and polar residues likely play
      a role in fibrillar assembly and interactions with other extracellular
      components.

PMID- 18805791
TI  - Asymmetry in the lipid affinity of bihelical amphipathic peptides. A structural
      determinant for the specificity of ABCA1-dependent cholesterol efflux by
      peptides.
AB  - ApoA-I contains a tandem array of amphipathic helices with varying lipid
      affinity, which are critical in its ability to bind and remove lipids from cells
      by the ABCA1 transporter. In this study, the effect of asymmetry in the lipid
      affinity of amphipathic helices in a bihelical apoA-I mimetic peptide, 37pA, on
      lipid efflux by the ABCA1 transporter was examined. Seven peptide variants of
      37pA were produced by substituting a varying number of hydrophobic amino acids
      for alanine on either one or both helices. The 5A peptide with five alanine
      substitutions in the second helix had decreased helical content compared with
      37pA (5A, 12+/-1% helicity; 37pA, 28+/-2% helicity) and showed less self
      association but, similar to the parent peptide, was able to readily solubilize
      phospholipid vesicles. Furthermore, 5A, unlike the parent peptide 37pA, was not
      hemolytic (37pA, 27+/-2% RBC lysis, 2 h, 18 microm). Finally, the 5A peptide
      stimulated cholesterol and phospholipid efflux by the ABCA1 transporter with
      higher specificity (ABCA1-transfected versus untransfected cells) than 37pA (5A,
      9.7+/-0.77%, 18 h, 18 microm versus 1.5+/-0.27%, 18 h, 18 microm (p<0.0001);
      37pA, 7.4+/-0.85%, 18 h, 18 microm versus 5.8+/-0.20%, 18 h, 18 microm (p=0.03)).
      In summary, we describe a novel bihelical peptide with asymmetry in the lipid
      affinity of its helices and properties similar to apoA-I in terms of specificity
      for cholesterol efflux by the ABCA1 transporter and low cytotoxicity.

PMID- 18805792
TI  - Defining the in Vivo Role for cytochrome b5 in cytochrome P450 function through
      the conditional hepatic deletion of microsomal cytochrome b5.
AB  - In vitro, cytochrome b5 modulates the rate of cytochrome P450-dependent mono
      oxygenation reactions. However, the role of this enzyme in determining drug
      pharmacokinetics in vivo and the consequential effects on drug absorption
      distribution, metabolism, excretion, and toxicity are unclear. In order to
      resolve this issue, we have carried out the conditional deletion of microsomal
      cytochrome b5 in the liver to create the hepatic microsomal cytochrome b5 null
      mouse. These mice develop and breed normally and have no overt phenotype. In
      vitro studies using a range of substrates for different P450 enzymes showed that
      in hepatic microsomal cytochrome b5 null NADH-mediated metabolism was essentially
      abolished for most substrates, and the NADPH-dependent metabolism of many
      substrates was reduced by 50-90%. This reduction in metabolism was also reflected
      in the in vivo elimination profiles of several drugs, including midazolam,
      metoprolol, and tolbutamide. In the case of chlorzoxazone, elimination was
      essentially unchanged. For some drugs, the pharmacokinetics were also markedly
      altered; for example, when administered orally, the maximum plasma concentration
      for midazolam was increased by 2.5-fold, and the clearance decreased by 3.6-fold
      in hepatic microsomal cytochrome b5 null mice. These data indicate that
      microsomal cytochrome b5 can play a major role in the in vivo metabolism of
      certain drugs and chemicals but in a P450- and substrate-dependent manner.

PMID- 18805793
TI  - Human T-cell leukemia virus type 1 HBZ protein bypasses the targeting function of
      ubiquitination.
AB  - Human T-cell leukemia virus type 1 (HTLV-1) encodes an antisense viral gene
      product termed HTLV-1 basic leucine-zipper factor (HBZ). HBZ forms heterodimers
      with c-Jun, a member of the AP-1 family, and promotes its proteasomal
      degradation. Although most proteasomal substrates are targeted for degradation
      via conjugation of polyubiquitin chains, we show that ubiquitination is not
      required for HBZ-mediated proteasomal degradation of c-Jun. We demonstrate that
      HBZ directly interacts with both the 26 S proteasome and c-Jun and facilitates
      the delivery of c-Jun to the proteasome without ubiquitination. HBZ acts as a
      tethering factor between the 26 S proteasome and its substrate, thereby bypassing
      the targeting function of ubiquitination. These findings disclose a novel viral
      strategy to utilize the cellular proteolytic system for viral propagation.

PMID- 18805794
TI  - Ajuba functions as a histone deacetylase-dependent co-repressor for
      autoregulation of the growth factor-independent-1 transcription factor.
AB  - Growth factor independent-1 (Gfi1) is a zinc finger protein with a SNAG
      transcriptional repressor domain. Ajuba is a LIM domain protein that shuttles
      between the cytoplasm and the nucleus. Ajuba functions as a co-repressor for
      synthetic Gfi1 SNAG-repressor domain-containing constructs, but a role for Ajuba
      co-repression of the cognate DNA bound Gfi1 protein has not been defined. Co
      immunoprecipitation of synthetic and endogenous proteins and co-elution with gel
      filtration suggest that an endogenous Ajuba.Gfi1.HDAC multiprotein complex is
      possible. Active histone deacetylase activity co-immunoprecipitates with Ajuba or
      Gfi1, and both proteins depend upon histone deacetylases for full transcriptional
      repression activity. Ajuba LIM domains directly bind to Gfi1, but the association
      is not SNAG domain-dependent. ChIP analysis and reciprocal knockdown experiments
      suggest that Ajuba selectively functions as a co-repressor for Gfi1
      autoregulation. The data suggest that Ajuba is utilized as a corepressor
      selectively on Gfi1 target genes.

PMID- 18805795
TI  - Pigment epithelium-derived factor binds to hyaluronan. Mapping of a hyaluronan
      binding site.
AB  - Pigment epithelium-derived factor (PEDF) is a multifunctional serpin with
      antitumorigenic, antimetastatic, and differentiating activities. PEDF is found
      within tissues rich in the glycosaminoglycan hyaluronan (HA), and its amino acid
      sequence contains putative HA-binding motifs. We show that PEDF coprecipitation
      with glycosaminoglycans in media conditioned by human retinoblastoma Y-79 cells
      decreased after pretreatments with hyaluronidase, implying an association between
      HA and PEDF. Direct binding of human recombinant PEDF to highly purified HA was
      demonstrated by coprecipitation in the presence of cetylpyridinium chloride.
      Binding of PEDF to HA was concentration-dependent and saturable. The PEDF-HA
      interactions were sensitive to increasing NaCl concentrations, indicating an
      ionic nature of these interactions and having affinity higher than PEDF-heparin.
      Competition assays showed that PEDF can bind heparin and HA simultaneously. PEDF
      chemically modified with fluorescein retained the capacity for interacting with
      HA but lacked heparin affinity, suggesting one or more distinct HA-binding
      regions on PEDF. The HA-binding region was examined by site-directed mutagenesis.
      Single-point and cumulative alterations at basic residues within the putative HA
      binding motif K189A/K191A/R194A/K197A drastically reduced the HA-binding activity
      without affecting heparin- or collagen I binding of PEDF. Cumulative alterations
      at sites critical for heparin binding (K146A/K147A/R149A) decreased HA affinity
      but not collagen I binding. Thus these clusters of basic residues (BXBXXBXXB and
      BX3AB2XB motifs) in PEDF are functional regions for binding HA. In the spatial
      PEDF structure they are located in distinct areas away from the collagen-binding
      site. The HA-binding activity of PEDF may contribute to deposition in the
      extracellular matrix and to its reported antitumor/antimetastatic effects.

PMID- 18805796
TI  - Ferritin contains less iron (59Fe) in cells when the protein pores are unfolded
      by mutation.
AB  - Ferric minerals in ferritins are protected from cytoplasmic reductants and Fe2+
      release by the protein nanocage until iron need is signaled. Deletion of ferritin
      genes is lethal; two critical ferritin functions are concentrating iron and
      oxidant protection (consuming cytoplasmic iron and oxygen in the mineral). In
      solution, opening/closing (gating) of eight ferritin protein pores controls
      reactions between external reductant and the ferritin mineral; pore gating is
      altered by mutation, low heat, and physiological urea (1 mm) and monitored by CD
      spectroscopy, protein crystallography, and Fe2+ release rates. To study the
      effects of a ferritin pore gating mutation in living cells, we cloned/expressed
      human ferritin H and H L138P, homologous to the frog open pore model that was
      unexpressable in human cells. Human ferritin H L138P behaved like the open pore
      ferritin model in vitro as follows: (i) normal protein cage assembly and
      mineralization, (ii) increased iron release (t1/2) decreased 17-fold), and (iii)
      decreased alpha-helix (8%). Overexpression (> 4-fold), in HeLa cells, showed for
      ferritin H L138P equal protein expression and total cell 59Fe but increased
      chelatable iron, 16%, p < 0.01 (59Fe in the deferoxamine-containing medium), and
      decreased 59Fe in ferritin, 28%, p < 0.01, compared with wild type. The
      coincidence of decreased 59Fe in open pore ferritin with increased chelatable
      59Fe in cells expressing the ferritin open pore mutation suggests that ferritin
      pore gating influences to the amount of iron (59Fe) in ferritin in vivo.

PMID- 18805797
TI  - Optimal stepwise experimental design for pairwise functional interaction studies.
AB  - MOTIVATION: Pairwise experimental perturbation is increasingly used to probe gene
      and protein function because these studies offer powerful insight into the
      activity and regulation of biological systems. Symmetric two-dimensional
      datasets, such as pairwise genetic interactions are amenable to an optimally
      designed measurement procedure because of the equivalence of cases and conditions
      where fewer experimental measurements may be required to extract the underlying
      structure. RESULTS: We show that optimal experimental design can provide
      improvements in efficiency when collecting data in an iterative manner. We
      develop a method built on a statistical clustering model for symmetric data and
      the Fisher information uncertainty estimates, and we also provide simple
      heuristic approaches that have comparable performance. Using yeast epistatic
      miniarrays as an example, we show that correct assignment of the major
      subnetworks could be achieved with <50% of the measurements in the complete
      dataset. Optimization is likely to become critical as pairwise functional studies
      extend to more complex mammalian systems where all by all experiments are
      currently intractable.

PMID- 18805798
TI  - MS-BID: a Java package for label-free LC-MS-based comparative proteomic analysis.
AB  - MS-BID (MS Biomarker Discovery Platform) is an integrative computational pipeline
      for biomarker discovery using LC-MS-based comparative proteomic analysis. This
      platform consists of several computational tools for: (i) detecting peptides in
      the collected patterns; (ii) matching detected peptides across a number of LC-MS
      datasets and (iii) selecting discriminatory peptides between classes of samples.
      AVAILABILITY: MS-BID source codes, binaries and documentations are freely
      available under LGPL from http://tools.proteomecenter.org/msBID.php.

PMID- 18805799
TI  - Relaxin signalling in primary cultures of human myometrial cells.
AB  - In myometrium of pigs and rats, though not humans, relaxin appears to mediate an
      inhibition of spontaneous and oxytocin-induced contractility, presumably acting
      through a G-protein coupled receptor (RXFP1) to generate cAMP. In humans,
      circulating relaxin is highest in the first trimester, including the time of
      implantation, when transitory uterine quiescence could help a blastocyst to
      implant. We investigated whether relaxin can activate adenylate cyclase in
      primary human myometrial cells from non-pregnant tissue, and we show that relaxin
      is able to stimulate the generation of cAMP in a manner, which is dependent upon
      a tyrosine phosphorylation activity, as in the endometrium. We identified
      transcripts for the relaxin receptor RXFP1 as full-length variants, though a
      minor splice variant missing exon 2 was also present in low amounts. These cells
      also express transcripts encoding RXFP2, the receptor for the closely related
      hormone, INSL3. Although able to respond to relaxin at high concentrations, this
      receptor does not appear to function by contributing to the cAMP production in
      human myometrial cells, nor does INSL3 act as a functional agonist or antagonist
      of relaxin action. In conclusion, the inability of relaxin to inhibit
      contractility in human myometrial cells would appear to be due to events
      downstream of simple cAMP generation.

PMID- 18805800
TI  - Increased levels of pregnancy-associated plasma protein-A2 in the serum of pre
      eclamptic patients.
AB  - Pregnancy-associated plasma protein-A and -A2 (PAPP-A and -A2) are proteases that
      cleave insulin-like growth factor-binding proteins (IGFBPs), resulting in local
      activation of IGF signaling pathways. Here, we examined PAPP-A and -A2 mRNA and
      protein levels in placenta and maternal sera from women with pre-eclampsia and
      compared them with samples from uncomplicated pregnancy. PAPP-A2 but not PAPP-A
      mRNA and protein were elevated in pre-eclamptic placenta (P < 0.01). PAPP-A2 is
      normally produced in placental syncytiotrophoblast cells and maternal decidua.
      PAPP-A2 in syncytiotrophoblast cells was dramatically increased in pre-eclampsia.
      Maternal serum concentrations of PAPP-A2 but not PAPP-A were also significantly
      elevated in pre-eclampsia as compared with uncomplicated pregnancy. mRNA levels
      of IGFBP5, a specific substrate for PAPP-A2 protease activity, were also
      significantly increased, suggesting a potential role for IGFBP5 in fetal and
      placental growth suppression during pre-eclampsia. However, IGFBP5 protein levels
      were not increased in placenta from pre-eclampsia, possibly due to cleavage by up
      regulated PAPP-A2. These data might imply that PAPP-A2 may be up-regulated in pre
      eclamptic pregnancy to compensate for IGFBP5-mediated suppression of the IGF
      pathway, although final birthweights are still low in pre-eclamptic pregnancy.

PMID- 18805801
TI  - Validation of preimplantation genetic diagnosis by PCR analysis: genotype
      comparison of the blastomere and corresponding embryo, implications for clinical
      practice.
AB  - The aim of this study was to validate the overall preimplantation genetic
      diagnosis (PGD)-PCR procedure and to determine the diagnostic value. Genotyped
      embryos not selected for embryo transfer (ET) and unsuitable for cryopreservation
      after PGD were used for confirmatory analysis. The PGD genotyped blastomeres and
      corresponding embryos were compared, and morphology was scored on Day 4 post
      fertilization. To establish the validity of the PGD-PCR procedure and the
      diagnostic value, misdiagnosis rate, false-negative rate and negative predictive
      value were calculated. Moreover, comparison on the validity was made for the
      biopsy of one or two blastomeres. For the total embryo group (n = 422), a
      misdiagnosis rate of 7.1% and a false-negative rate of 3.1% were found. The
      negative predictive value was 96.1%. Poor morphology Day 4 embryos (Class 1) were
      over-represented in the embryo group in which the blastomere genotype was not
      confirmed by the whole embryo genotype. The misdiagnosis rate of Class 1 embryos
      was 12.5% and the false-negative rate 17.1%. Exclusion of these embryos resulted
      in a misdiagnosis rate of 6.1%, a false-negative rate of 0.5% and a negative
      predictive value of 99.3%. The two blastomere biopsies revealed a significant
      higher positive predictive value, lowering the misdiagnosis rate, whereas the
      negative predictive value remained the same. In conclusion, the PGD-PCR procedure
      is a valid diagnostic method to select unaffected embryos for ET. The
      misdiagnosis and false-negative rates decrease by rejecting Class 1 embryos for
      ET. The biopsy of a second blastomere improves the positive predictive value,
      lowering the misdiagnosis rate.

PMID- 18805802
TI  - Comment on 'From risk factors to explanation in public health'.

PMID- 18805803
TI  - Age-related retinal degeneration (arrd2) in a novel mouse model due to a nonsense
      mutation in the Mdm1 gene.
AB  - We observed that a naturally occurring mouse strain developed age-related retinal
      degeneration (arrd2). These mice had normal fundi, electroretinograms (ERGs) and
      retinal histology at 6 months of age; vessel attenuation, RPE atrophy and
      pigmentary abnormalities at 14 months, which progressed to complete loss of
      photoreceptors and extinguished ERG by 22 months. Genetic analysis revealed that
      the retinal degeneration in arrd2 segregates in an autosomal recessive manner and
      the disease gene localizes to mouse chromosome 10. A positional candidate cloning
      approach detected a nonsense mutation in the mouse double minute-1 gene (Mdm1),
      which results in the truncation of the putative protein from 718 amino acids to
      398. We have identified a novel transcript of the Mdm1 gene, which is the
      predominant transcript in the retina. The Mdm1 transcript is localized to the
      nuclear layers of neural retina. Expression of Mdm1 in the retina increases
      steadily from post-natal day 30 to 1 year, and a high level of Mdm1 are
      subsequently maintained. The Mdm1 transcript was found to be significantly
      depleted in the retina of arrd2 mice and the transcript was observed to degrade
      by nonsense-mediated decay. These results indicate that the depletion of the Mdm1
      transcript may underlie the mechanism leading to late-onset progressive retinal
      degeneration in arrd2 mice. Analysis of a cohort of patients with age-related
      macular degeneration (AMD) wherein the susceptibility locus maps to chromosome
      12q, a region bearing the human ortholog to MDM1, did not reveal association
      between human MDM1 and AMD.

PMID- 18805804
TI  - Cellular mechanisms of Cnidarian bleaching: stress causes the collapse of
      symbiosis.
AB  - Cnidarian bleaching is a breakdown in the mutualistic symbiosis between host
      Cnidarians, such as reef building corals, and their unicellular photosynthetic
      dinoflagellate symbionts. Bleaching is caused by a variety of environmental
      stressors, most notably elevated temperatures associated with global climate
      change in conjunction with high solar radiation, and it is a major contributor to
      coral death and reef degradation. This review examines the underlying cellular
      events that lead to symbiosis dysfunction and cause bleaching, emphasizing that,
      to date, we have only some pieces of a complex cellular jigsaw puzzle. Reactive
      oxygen species (ROS), generated by damage to both photosynthetic and
      mitochondrial membranes, is shown to play a central role in both injury to the
      partners and to inter-partner communication of a stress response. Evidence is
      presented that suggests that bleaching is a host innate immune response to a
      compromised symbiont, much like innate immune responses in other host-microbe
      interactions. Finally, the elimination or exit of the symbiont from host tissues
      is described through a variety of mechanisms including exocytosis, host cell
      detachment and host cell apoptosis.

PMID- 18805805
TI  - Larval anopheline mosquito recta exhibit a dramatic change in localization
      patterns of ion transport proteins in response to shifting salinity: a comparison
      between anopheline and culicine larvae.
AB  - Mosquito larvae live in dynamic aqueous environments, which can fluctuate
      drastically in salinity due to environmental events such as rainfall and
      evaporation. Larval survival depends upon the ability to regulate hemolymph
      osmolarity by absorbing and excreting ions. A major organ involved in ion
      regulation is the rectum, the last region for modification of the primary urine
      before excretion. The ultrastructure and function of culicine larval recta have
      been studied extensively; however, very little published data exist on the recta
      of anopheline larvae. To gain insight into the structure and functions of this
      organ in anopheline species, we used immunohistochemistry to compare the
      localization of three proteins [carbonic anhydrase (CA9), Na+/K+ P-ATPase and H+
      V-ATPase] in the recta of anopheline larvae reared in freshwater and saline water
      with the localization of the same proteins in culicine larvae reared under
      similar conditions. Based on the following key points, we concluded that
      anophelines differ from culicines in larval rectal structure and in regulation of
      protein expression: (1) despite the fact that obligate freshwater and saline
      tolerant culicines have structurally distinct recta, all anophelines examined
      (regardless of saline-tolerance) have a structurally similar rectum consisting of
      distinct DAR (dorsal anterior rectal) cells and non-DAR cells; (2) anopheline
      larvae undergo a dramatic shift in rectal Na+/K+-ATPase localization when reared
      in freshwater vs saline water. This shift is not seen in any culicine larvae
      examined. Additionally, we use these immunohistochemical analyses to suggest
      possible functions for the DAR and non-DAR cells of anopheline larvae in
      freshwater and saline conditions.

PMID- 18805806
TI  - Effects of hypothermia on gene expression in zebrafish gills: upregulation in
      differentiation and function of ionocytes as compensatory responses.
AB  - Ectothermic vertebrates are different from mammals that are sensitive to
      hypothermia and have to maintain core temperature for survival. Why and how
      ectothermic animals survive, grow and reproduce in low temperature have been for
      a long time a scientifically challenging and important inquiry to biologists. We
      used a microarray to profile the gill transcriptome in zebrafish (Danio rerio)
      after exposure to low temperature. Adult zebrafish were acclimated to a low
      temperature of 12 degrees C for 1 day and up to 30 days, and the gill
      transcriptome was compared with that of control fish in 28 degrees C by
      oligonucleotide microarray hybridization. Results showed 11 and 22 transcripts
      were found to be upregulated, whereas 56 and 70 transcripts were downregulated by
      low-temperature treatment for 1 day and 30 days, respectively. The gill
      transcriptome profiles revealed that ionoregulation-related genes were highly
      upregulated in cold-acclimated zebrafish. This paved the way to investigate the
      role of ionoregulatory genes in zebrafish gills during cold acclimation. Cold
      acclimation caused upregulation of genes that are essential for ionocyte
      specification, differentiation, ionoregulation, acid-base balance and the number
      of cells expressing these genes increased. For instance, epithelial Ca2+ channel
      (EcaC; an ionoregulatory protein) mRNA increased in parallel with the level of
      Ca2+ influx, revealing a functional compensation after long-term acclimation to
      cold. Phosphohistone H3 and TUNEL staining showed that the cell turnover rate was
      retarded in cold-acclimated gills. Altogether, these results suggest that gills
      may sustain their functions by producing mature ionocytes from pre-existing
      undifferentiated progenitors in low-temperature environments.

PMID- 18805807
TI  - Frontal sinuses and head-butting in goats: a finite element analysis.
AB  - Frontal sinuses in goats and other mammals have been hypothesized to function as
      shock absorbers, protecting the brain from blows during intraspecific combat.
      Furthermore, sinuses are thought to form through removal of ;structurally
      unnecessary' bone. These hypotheses were tested using finite element modeling.
      Three-dimensional models of domesticated goat (Capra hircus) skulls were
      constructed, with variable frontal bone and frontal sinus morphology, and loaded
      to simulate various head-butting behaviors. In general, models with sinuses
      experienced higher strain energy values (a proxy for shock absorption) than did
      models with unvaulted frontal bones, and the latter often had higher magnitudes
      than models with solid vaulted frontal bones. Furthermore, vaulted frontal bones
      did not reduce magnitudes of principal strain on the surface of the endocranial
      cavity relative to models with unvaulted frontal bones under most loading
      conditions. Thus, these results were only partially consistent with sinuses, or
      the bone that walls the sinuses, acting as shock absorbers. It is hypothesized
      that the keratinous horn sheaths and cranial sutures are probably more important
      for absorbing blows to the head. Models with sinuses did exhibit a more
      ;efficient' distribution of stresses, as visualized by histograms in which models
      with solid frontal bones had numerous unloaded elements. This is consistent with
      the hypothesis that sinuses result at least in part from the removal of
      mechanically unnecessary bone.

PMID- 18805808
TI  - Fluid dynamics of feeding behaviour in white-spotted bamboo sharks.
AB  - Although the motor control of feeding is presumed to be generally conserved, some
      fishes are capable of modulating the feeding behaviour in response to prey type
      and or prey size. This led to the 'feeding modulation hypothesis', which states
      that rapid suction strikes are pre-programmed stereotyped events that proceed to
      completion once initiated regardless of sensory input. If this hypothesis holds
      true, successful strikes should be indistinguishable from unsuccessful strikes
      owing to a lack of feedback control in specialized suction feeding fishes. The
      hydrodynamics of suction feeding in white-spotted bamboo sharks (Chiloscyllium
      plagiosum) was studied in three behaviours: successful strikes, intraoral
      transports of prey and unsuccessful strikes. The area of the fluid velocity
      region around the head of feeding sharks was quantified using time-resolved
      digital particle image velocimetry (DPIV). The maximal size of the fluid velocity
      region is 56% larger in successful strikes than unsuccessful strikes (10.79 cm2
      vs 6.90 cm2), but they do not differ in duration, indicating that strikes are
      modulated based on some aspect of the prey or simply as a result of decreased
      effort on the part of the predator. The hydrodynamic profiles of successful and
      unsuccessful strikes differ after 21 ms, a period probably too short to provide
      time to react through feedback control. The predator-to-prey distance is larger
      in missed strikes compared with successful strikes, indicating that insufficient
      suction is generated to compensate for the increased distance. An accuracy index
      distinguishes unsuccessful strikes (-0.26) from successful strikes (0.45 to
      0.61). Successful strikes occur primarily between the horizontal axis of the
      mouth and the dorsal boundary of the ingested parcel of water, and missed prey
      are closer to the boundary or beyond. Suction transports are shorter in duration
      than suction strikes but have similar maximal fluid velocity areas to move the
      prey through the oropharyngeal cavity into the oesophagus (54 ms vs 67 ms).

PMID- 18805809
TI  - A glucagon-like endocrine pathway in Drosophila modulates both lipid and
      carbohydrate homeostasis.
AB  - The regulation of energy homeostasis is fundamental to all organisms. The
      Drosophila fat body serves as a repository for both triglycerides and glycogen,
      combining the energy storage functions of mammalian adipose and hepatic tissues,
      respectively. Here we show that mutation of the Drosophila adipokinetic hormone
      receptor (AKHR), a functional analog of the mammalian glucagon receptor, leads to
      abnormal accumulation of both lipid and carbohydrate. As a consequence of their
      obese phenotypes, AKHR mutants are markedly starvation resistant. We show that
      AKHR is expressed in the fat body, and, intriguingly, in a subset of gustatory
      neurons that mediate sweet taste. Genetic rescue experiments establish that the
      metabolic phenotypes arise exclusively from the fat body AKHR expression.
      Behavioral experiments demonstrate that AKHR mutants are neither sedentary nor
      hyperphagic, suggesting the metabolic abnormalities derive from a genetic
      propensity to retain energy stores. Taken together, our results indicate that a
      single endocrine pathway contributes to both lipid and carbohydrate catabolism in
      the Drosophila fat body.

PMID- 18805810
TI  - AMP-activated protein kinase activity during metabolic rate depression in the
      hypoxic goldfish, Carassius auratus.
AB  - Cell survival during hypoxia exposure requires a metabolic reorganization to
      decrease ATP demands to match the reduced capacity for ATP production. We
      investigated whether AMP-activated protein kinase (AMPK) activity responds to 12
      h exposure to severe hypoxia ( approximately 0.3 mg O2 l(-1)) in the anoxia
      tolerant goldfish (Carassius auratus). Hypoxia exposure in goldfish was
      characterized by a strong activation of creatine phosphate hydrolysis and
      glycolysis in liver and muscle. AMPK activity increased by approximately 5.5-fold
      in goldfish liver within 0.5 h hypoxia exposure and this increase in activity was
      temporally associated with an 11-fold increase in [AMP(free)]/[ATP]. No changes
      in total AMPK protein amount were observed, suggesting that the changes in AMPK
      activity are due to post-translational phosphorylation of the protein. Hypoxia
      exposure had no effect on the expression of two identified AMPK alpha-subunit
      isoforms and caused an approximately 50% decrease in the mRNA levels of AMPK beta
      subunit isoform. Changes in AMPK activity in the liver were associated with an
      increase in percentage phosphorylation of a well-characterized target of AMPK,
      eukaryotic elongation factor-2 (eEF2), and decreases in protein synthesis rates
      measured in liver cell-free extracts. No activation of AMPK was observed in
      muscle, brain, heart or gill during the 12 h hypoxia exposure suggesting a tissue
      specific regulation of AMPK possibly related to a lack of change in cellular
      [AMP(free)]/[ATP] as observed in muscle.

PMID- 18805811
TI  - African penguins (Spheniscus demersus) can detect dimethyl sulphide, a prey
      related odour.
AB  - Although it is well established that certain procellariiform seabirds use odour
      cues to find prey, it is not clear whether penguins use olfactory cues to forage.
      It is commonly assumed that penguins lack a sense of smell, yet they are closely
      related to procellariiforms and forage on similar types of prey in similar areas
      to many procellariiforms. Such regions are characterized by having high levels of
      dimethyl sulphide (DMS) a scented compound that many marine animals use to locate
      foraging grounds. If penguins can smell, DMS may be a biologically relevant
      scented compound that they may be sensitive to in nature. To test this
      hypothesis, we investigated whether adult African penguins (Spheniscus demersus)
      could detect DMS using two separate experiments. We tested wild penguins on
      Robben Island, South Africa, by deploying mumolar DMS solutions in the colonies,
      and found that birds slowed down their walking speeds. We also tested captive
      penguins in a Y-maze. In both cases, our data convincingly demonstrate that
      African penguins have a functioning sense of smell and are attracted to DMS. The
      implication of this work is that the detection of changes in the odour landscape
      (DMS) may assist penguins in identifying productive areas of the ocean for
      foraging. At-sea studies are needed to investigate this issue further.

PMID- 18805812
TI  - Suction generation in white-spotted bamboo sharks Chiloscyllium plagiosum.
AB  - After the divergence of chondrichthyans and teleostomes, the structure of the
      feeding apparatus also diverged leading to alterations in the suction mechanism.
      In this study we investigated the mechanism for suction generation during feeding
      in white-spotted bamboo sharks, Chiloscyllium plagiosum and compared it with that
      in teleosts. The internal movement of cranial elements and pressure in the
      buccal, hyoid and pharyngeal cavities that are directly responsible for suction
      generation was quantified using sonomicrometry and pressure transducers. Backward
      stepwise multiple linear regressions were used to explore the relationship
      between expansion and pressure, accounting for 60-96% of the variation in
      pressure among capture events. The progression of anterior to posterior expansion
      in the buccal, hyoid and pharyngeal cavities is accompanied by the sequential
      onset of subambient pressure in these cavities as prey is drawn into the mouth.
      Gape opening triggers the onset of subambient pressure in the oropharyngeal
      cavities. Peak gape area coincides with peak subambient buccal pressure.
      Increased velocity of hyoid area expansion is primarily responsible for
      generating peak subambient pressure in the buccal and hyoid regions. Pharyngeal
      expansion appears to function as a sink to receive water influx from the mouth,
      much like that of compensatory suction in bidirectional aquatic feeders.
      Interestingly, C. plagiosum generates large suction pressures while paradoxically
      compressing the buccal cavity laterally, delaying the time to peak pressure. This
      represents a fundamental difference from the mechanism used to generate suction
      in teleost fishes. Interestingly, pressure in the three cavities peaks in the
      posterior to anterior direction. The complex shape changes that the buccal cavity
      undergoes indicate that, as in teleosts, unsteady flow predominates during
      suction feeding. Several kinematic variables function together, with great
      variation over long gape cycles to generate the low subambient pressures used by
      C. plagiosum to capture prey.

PMID- 18805813
TI  - Investigating onychophoran gas exchange and water balance as a means to inform
      current controversies in arthropod physiology.
AB  - Several controversies currently dominate the fields of arthropod metabolic rate,
      gas exchange and water balance, including the extent to which modulation of gas
      exchange reduces water loss, the origins of discontinuous gas exchange, the
      relationship between metabolic rate and life-history strategies, and the causes
      of Palaeozoic gigantism. In all of these areas, repeated calls have been made for
      the investigation of groups that might most inform the debates, especially of
      taxa in key phylogenetic positions. Here we respond to this call by investigating
      metabolic rate, respiratory water loss and critical oxygen partial pressure (Pc)
      in the onychophoran Peripatopsis capensis, a member of a group basal to the
      arthropods, and by synthesizing the available data on the Onychophora. The rate
      of carbon dioxide release (VCO2) at 20 degrees C in P. capensis is 0.043 ml CO2
      h(-1), in keeping with other onychophoran species; suggesting that low metabolic
      rates in some arthropod groups are derived. Continuous gas exchange suggests that
      more complex gas exchange patterns are also derived. Total water loss in P.
      capensis is 57 mg H2O h(-1) at 20 degrees C, similar to modern estimates for
      another onychophoran species. High relative respiratory water loss rates (
      approximately 34%; estimated using a regression technique) suggest that the basal
      condition in arthropods may be a high respiratory water loss rate. Relatively
      high Pc values (5-10% O2) suggest that substantial safety margins in insects are
      also a derived condition. Curling behaviour in P. capensis appears to be a
      strategy to lower energetic costs when resting, and the concomitant depression of
      water loss is a proximate consequence of this behaviour.

PMID- 18805814
TI  - Pitching stabilization via caudal fin-wave propagation in a forward-sinking
      parrot cichlid (Cichlasoma citrinellum x Cichlasoma synspilum).
AB  - Caudal fin-wave propagation (CFP) is a commonly observed behavior in a fish but
      has been little investigated. Our objective is to understand the function of a
      CFP for a forward-sinking parrot cichlid that adopts a tilted-down swimming
      posture. We utilized stereoscopic digital particle-image velocimetry to measure
      the velocity fields in the wake of both the caudal fin and the pectoral fins and
      to evaluate the corresponding hydrodynamic forces. The tilted-down posture of
      this fish is inherently unstable because of the presence of the head-down
      pitching moment induced from the buoyant force of the body. The down-stroke of
      the pectoral fins results also in a head-down pitching moment that destabilizes
      the fish. Our results indicate that a CFP facilitates the pitching stabilization
      of a fish. In a forward-sinking parrot cichlid, a CFP produces periodic jets (CFP
      jets) that are oriented laterally and posterodorsally, which result in both
      thrust and negative lift that induce a head-up pitching moment. The CFP jets are
      initially trapped by the ventral part of the caudal fin, strengthened and
      reoriented by the dorsally propagating fin wave, and expelled near the dorsal
      part of the caudal fin.

PMID- 18805815
TI  - Natural variation in plasticity of glucose homeostasis and food intake.
AB  - Balancing the acquisition, allocation and storage of energy during periods of
      food deprivation is critical for survival. We show that natural variation in the
      foraging (for) gene, which encodes a cGMP-dependent protein kinase (PKG) in the
      fruit fly Drosophila melanogaster, affects behavioral and physiological responses
      to short-term food deprivation. Rover and sitter, natural allelic variants of
      for, differ in their stored carbohydrate reserves as well as their response to
      short-term deprivation. Fewer carbohydrates are stored in the fat body of rovers
      compared with sitters, and more labeled glucose is allocated to lipid stores
      compared with carbohydrate stores during a short feeding bout. Short-term food
      deprivation decreases hemolymph glucose levels in rovers but not in sitters.
      After food deprivation, rovers increase their food intake more slowly than
      sitters, and rover hemolymph levels take longer to respond to re-feeding.
      Finally, rovers have lower adipokinetic hormone (akh) mRNA levels than sitters.
      Our data suggest that for mediates larval responses to short-term food
      deprivation by altering food intake and blood glucose levels.

PMID- 18805816
TI  - Effects of [Ca2+]i and pH on epithelial Na+ channel activity of cultured mouse
      cortical collecting ducts.
AB  - [Ca2+]i and pH have been demonstrated to affect Na+ transport in epithelium
      mediated via the apical epithelial Na+ channel (ENaC). However, it still remains
      unclear whether the effects of [Ca2+]i and intracellular pH (pHi) on ENaC
      activity are direct. In this study, inside-out recording was employed to clarify
      the effects of pH(i) and [Ca2+]i on ENaC activity. We found that elevation of
      [Ca2+]i induced a significant inhibition of ENaC open probability without
      altering channel conductance. The inhibitory effect was due to a direct
      interaction between Ca2+ and ENaC, and is dependent on [Ca2+]i. pHi also directly
      regulated ENaC open probability. Lower pHi (<7.0) reduced the ENaC open
      probability as shown in shorter opening time, and higher pH(i) (>7.0) enhanced
      the ENaC open probability as shown in augmented opening time. pHi did not cause
      any alteration in channel conductance. The effects of pHi on ENaC open
      probability could be summarized as an S-shaped curve around pH 7.2.

PMID- 18805817
TI  - Foraging bats avoid noise.
AB  - Ambient noise influences the availability and use of acoustic information in
      animals in many ways. While much research has focused on the effects of noise on
      acoustic communication, here, we present the first study concerned with
      anthropogenic noise and foraging behaviour. We chose the greater mouse-eared bat
      (Myotis myotis) as a model species because it represents the especially
      vulnerable group of gleaning bats that rely on listening for prey rustling sounds
      to find food (i.e. 'passive listening'). In a choice experiment with two foraging
      compartments, we investigated the influence of background noise on foraging
      effort and foraging success. We tested the hypotheses that: (1) bats will avoid
      foraging areas with particularly loud background noise; and (2) the frequency
      time structure of the noise will determine, in part, the degree to which it
      deters bats. We found a clear effect of the type of noise on the allocation of
      foraging effort to the compartments and on the distribution of prey capture
      events. When playing back silence, the bats made equal use of and were equally
      successful in both compartments. In the other three treatments (where a non
      silent sound was played back), the bats avoided the playback compartment. The
      degree to which the background noise deterred bats from the compartment increased
      from traffic noise to vegetation movement noise to broadband computer-generated
      noise. Vegetation noise, set 12 dB below the traffic noise amplitude, had a
      larger repellent effect; presumably because of its acoustic similarity with prey
      sounds. Our experimental data suggest that foraging areas very close to highways
      and presumably also to other sources of intense, broadband noise are degraded in
      their suitability as foraging areas for such 'passive listening' bats.

PMID- 18805818
TI  - The kinematic determinants of anuran swimming performance: an inverse and forward
      dynamics approach.
AB  - The aims of this study were to explore the hydrodynamic mechanism of Xenopus
      laevis swimming and to describe how hind limb kinematics shift to control
      swimming performance. Kinematics of the joints, feet and body were obtained from
      high speed video of X. laevis frogs (N=4) during swimming over a range of speeds.
      A blade element approach was used to estimate thrust produced by both
      translational and rotational components of foot velocity. Peak thrust from the
      feet ranged from 0.09 to 0.69 N across speeds ranging from 0.28 to 1.2 m s(-1).
      Among 23 swimming strokes, net thrust impulse from rotational foot motion was
      significantly higher than net translational thrust impulse, ranging from 6.1 to
      29.3 N ms, compared with a range of -7.0 to 4.1 N ms from foot translation.
      Additionally, X. laevis kinematics were used as a basis for a forward dynamic
      anuran swimming model. Input joint kinematics were modulated to independently
      vary the magnitudes of foot translational and rotational velocity. Simulations
      predicted that maximum swimming velocity (among all of the kinematics patterns
      tested) requires that maximal translational and maximal rotational foot velocity
      act in phase. However, consistent with experimental kinematics, translational and
      rotational motion contributed unequally to total thrust. The simulation powered
      purely by foot translation reached a lower peak stroke velocity than the pure
      rotational case (0.38 vs 0.54 m s(-1)). In all simulations, thrust from the foot
      was positive for the first half of the power stroke, but negative for the second
      half. Pure translational foot motion caused greater negative thrust (70% of peak
      positive thrust) compared with pure rotational simulation (35% peak positive
      thrust) suggesting that translational motion is propulsive only in the early
      stages of joint extension. Later in the power stroke, thrust produced by foot
      rotation overcomes negative thrust (due to translation). Hydrodynamic analysis
      from X. laevis as well as forward dynamics give insight into the differential
      roles of translational and rotational foot motion in the aquatic propulsion of
      anurans, providing a mechanistic link between joint kinematics and swimming
      performance.

PMID- 18805819
TI  - Systematic differences in membrane acyl composition associated with varying body
      mass in mammals occur in all phospholipid classes: an analysis of kidney and
      brain.
AB  - The acyl composition of membrane phospholipids in kidney and brain of mammals of
      different body mass was examined. It was hypothesized that reduction in
      unsaturation index (number of double bonds per 100 acyl chains) of membrane
      phospholipids with increasing body mass in mammals would be made-up of similar
      changes in acyl composition across all phospholipid classes and that phospholipid
      class distribution would be regulated and similar in the same tissues of the
      different-sized mammals. The results of this study supported both hypotheses.
      Differences in membrane phospholipid acyl composition (i.e. decreased omega-3
      fats, increased monounsaturated fats and decreased unsaturation index with
      increasing body size) were not restricted to any specific phospholipid molecule
      or to any specific phospholipid class but were observed in all phospholipid
      classes. With increase in body mass of mammals both monounsaturates and use of
      less unsaturated polyunsaturates increases at the expense of the long-chain
      highly unsaturated omega-3 and omega-6 polyunsaturates, producing decreases in
      membrane unsaturation. The distribution of membrane phospholipid classes was
      essentially the same in the different-sized mammals with phosphatidylcholine (PC)
      and phosphatidylethanolamine (PE) together constituting approximately 91% and
      approximately 88% of all phospholipids in kidney and brain, respectively. The
      lack of sphingomyelin in the mouse tissues and higher levels in larger mammals
      suggests an increased presence of membrane lipid rafts in larger mammals. The
      results of this study support the proposal that the physical properties of
      membranes are likely to be involved in changing metabolic rate.

PMID- 18805820
TI  - Spatiotemporal expression of transcriptional regulators in concert with the
      maternal-to-embryonic transition during bovine in vitro embryogenesis.
AB  - Cleavage-stage bovine embryos are transcriptionally quiescent until they reach
      the 8- to 16-cell stage, and thus rely on the reserves provided by the stored
      maternal mRNAs and proteins found in the oocytes to achieve their first cell
      divisions. The objective of this study was to characterize the expression and
      localization of the transcriptional and translational regulators, Y box binding
      protein 2 (YBX2), TATA box-binding protein (TBP), and activating transcription
      factor 2 (ATF2), during bovine early embryo development. Germinal vesicle (GV)-
      and metaphase II (MII)-stage oocytes, as well as 2-, 4-, 8-, 16-cell-stage
      embryos, morula, and blastocysts, produced in vitro were analyzed for temporal
      and spatial protein expression. Using Q-PCR, ATF2 mRNA expression was shown to
      remain constant from the GV-stage oocyte to the four-cell embryo, and then
      decreased through to the blastocyst stage. By contrast, the protein levels of
      ATF2 remained constant throughout embryo development and were found in both the
      cytoplasm and the nucleus. Both TBP and YBX2 showed opposite protein expression
      patterns, as YBX2 protein levels decreased throughout development, while TBP
      levels increased through to the blastocyst stage. Immunolocalization studies
      revealed that TBP protein was localized in the nucleus of 8- to 16-cell-stage
      embryos, whereas the translational regulator YBX2 was exclusively cytoplasmic and
      disappeared from the 16-cell stage onward. This study shows that YBX2, TBP, and
      ATF2 are differentially regulated through embryo development, and provides
      insight into the molecular events occurring during the activation of the bovine
      genome during embryo development in vitro.

PMID- 18805821
TI  - Genomic imprinting in marsupial placentation.
AB  - Genomic imprinting is a widespread epigenetic phenomenon in eutherian mammals,
      which regulates many aspects of growth and development. Parental conflict over
      the degree of maternal nutrient transfer is the favoured hypothesis for the
      evolution of imprinting. Marsupials, like eutherian mammals, are viviparous but
      deliver an altricial young after a short gestation supported by a fully
      functional placenta, so can shed light on the evolution and time of acquisition
      of genomic imprinting. All orthologues of eutherian imprinted genes examined have
      a conserved expression in the marsupial placenta regardless of their imprint
      status. Differentially methylated regions (DMRs) are the most common mechanism
      controlling genomic imprinting in eutherian mammals, but none were found in the
      marsupial imprinted orthologues of IGF2 receptor (IGF2R), INS or mesoderm
      specific transcript (MEST). Instead, histone modification appears to be the
      mechanism used to silence these genes. At least three genes in marsupials have
      DMRs: H19, IGF2 and PEG10. PEG10 is particularly interesting as it is derived
      from a retrotransposon, providing the first direct evidence that retrotransposon
      insertion can drive the evolution of an imprinted region and of a DMR in mammals.
      The insertion occurred after the prototherian-therian mammal divergence,
      suggesting that there may have been strong selection for the retention of
      imprinted regions that arose during the evolution of placentation. There is
      currently no evidence for genomic imprinting in the egg-laying monotreme mammals.
      However, since these mammals do have a short-lived placenta, imprinting appears
      to be correlated with viviparity but not placentation.

PMID- 18805822
TI  - Neonatal infections in Asia.
AB  - OBJECTIVE: To study the epidemiology (including incidence, antibiotic sensitivity
      and mortality) of neonatal unit infections in countries in Asia. METHODS: One
      year prospective study of neonatal infections in eight neonatal units in Asia.
      RESULTS: There were 453 episodes of sepsis affecting 394 babies. Mortality from
      neonatal sepsis was 10.4%, with an incidence of 0.69 deaths/1000 live births.
      Group B streptococcus was the most common early-onset organism causing 38% of
      episodes of early-onset (<48 h old) sepsis, with a rate of 0.51 episodes per 1000
      live births and a mortality of 22%. Gram-negative bacillary early-onset sepsis
      occurred at a rate of 0.15 episodes per 1000 live births with a mortality of 12%.
      There were 406 episodes of late-onset sepsis. The incidence was high at 11.6 per
      1000 live births, and mortality was 8.9%. Coagulase-negative staphylococcus
      caused 34.1% of episodes, whereas Staphylococcus aureus caused only 5.4%. Gram
      negative bacilli caused 189 episodes (46.6%). Only 44% of Gram-negative bacilli
      were sensitive to both gentamicin and a third-generation cephalosporin, whereas
      30% were resistant to both antibiotics. Meningitis occurred in 17.2% of episodes
      of late sepsis, with a mortality of 20%. CONCLUSIONS: The incidence of late-onset
      sepsis was higher in Asia than in resource-rich countries, but the organisms
      isolated and mortality were similar. Over half of all Gram-negative bacilli were
      antibiotic resistant.

PMID- 18805823
TI  - Investigating the variations in survival rates for very preterm infants in 10
      European regions: the MOSAIC birth cohort.
AB  - OBJECTIVE: To investigate the variation in the survival rate and the mortality
      rates for very preterm infants across Europe. DESIGN: A prospective birth cohort
      of very preterm infants for 10 geographically defined European regions during
      2003, followed to discharge home from hospital. PARTICIPANTS: All deliveries from
      22 + 0 to 31 + 6 weeks' gestation. MAIN OUTCOME MEASURE: All outcomes of
      pregnancy by gestational age group, including termination of pregnancy for
      congenital anomalies and other reasons, antepartum stillbirth, intrapartum
      stillbirth, labour ward death, death after admission to a neonatal intensive care
      unit (NICU) and survival to discharge. RESULTS: Overall the proportion of this
      very preterm cohort who survived to discharge from neonatal care was 89.5%,
      varying from 93.2% to 74.8% across the regions. Less than 2% of infants <24
      weeks' gestation and approximately half of the infants from 24 to 27 weeks'
      gestation survived to discharge home from the NICU. However large variations were
      seen in the timing of the deaths by region. Among all fetuses alive at onset of
      labour of 24-27 weeks' gestation, between 84.0% and 98.9% were born alive and
      between 64.6% and 97.8% were admitted to the NICU. For babies <24 weeks'
      gestation, between 0% and 79.6% of babies alive at onset of labour were admitted
      to neonatal intensive care. CONCLUSIONS: There are wide variations in the
      survival rates to discharge from neonatal intensive care for very preterm
      deliveries and in the timing of death across the MOSAIC regions. In order to
      directly compare international statistics for mortality in very preterm infants,
      data collection needs to be standardised. We believe that the standard point of
      comparison should be using all those infants alive at the onset of labour as the
      denominator for comparisons of mortality rates for very preterm infants analysing
      the cohort by gestational age band.

PMID- 18805824
TI  - Intelligence of very preterm or very low birthweight infants in young adulthood.
AB  - OBJECTIVE: To examine the effect of intrauterine and neonatal growth, prematurity
      and personal and environmental risk factors on intelligence in adulthood in
      survivors of the early neonatal intensive care era. METHODS: A large
      geographically based cohort comprised 94% of all babies born alive in the
      Netherlands in 1983 with a gestational age below 32 weeks and/or a birth weight
      >1500 g (POPS study). Intelligence was assessed in 596 participants at 19 years
      of age. Intrauterine and neonatal growth were assessed at birth and 3 months of
      corrected age. Environmental and personal risk factors were maternal age,
      education of the parent, sex and origin. RESULTS: The mean (SD) IQ of the cohort
      was 97.8 (15.6). In multiple regression analysis, participants with highly
      educated parents had a 14.2-point higher IQ than those with less well-educated
      parents. A 1 SD increase in birth weight was associated with a 2.6-point higher
      IQ, and a 1-week increase in gestational age was associated with a 1.3-point
      higher IQ. Participants born to young mothers (<25 years) had a 2.7-point lower
      IQ, and men had a 2.1-point higher IQ than women. The effect on intelligence
      after early (symmetric) intrauterine growth retardation was more pronounced than
      after later (asymmetric) intrauterine or neonatal growth retardation. These
      differences in mean IQ remained when participants with overt handicaps were
      excluded. CONCLUSIONS: Prematurity as well as the timing of growth retardation
      are important for later intelligence. Parental education, however, best predicted
      later intelligence in very preterm or very low birthweight infants.

PMID- 18805825
TI  - Six new coeliac disease loci replicated in an Italian population confirm
      association with coeliac disease.
AB  - BACKGROUND AND AIMS: The first genome wide association study on coeliac disease
      (CD) and its follow-up have identified eight new loci that contribute
      significantly towards CD risk. Seven of these loci contain genes controlling
      adaptive immune responses, including IL2/IL21 (4q27), RGS1 (1q31), IL18RAP (2q11
      2q12), CCR3 (3p21), IL12A (3q25-3q26), TAGAP (6q25) and SH2B3 (12q24). METHODS:
      We selected the nine most associated single nucleotide polymorphisms to tag the
      eight new loci in an Italian cohort comprising 538 CD patients and 593 healthy
      controls. RESULTS: Common variation in IL2/IL21, RGS1, IL12A/SCHIP and SH2B3 was
      associated with susceptibility to CD in our Italian cohort. The LPP and TAGAP
      regions also showed moderate association, whereas there was no association with
      CCR3 and IL18RAP. CONCLUSION: This is the first replication study of six of the
      eight new CD loci; it is also the first CD association study in a southern
      European cohort. Our results may imply there is a genuine population difference
      across Europe regarding the loci contributing to CD.

PMID- 18805826
TI  - Clinical experience in the evaluation of 30 patients with a prior diagnosis of FG
      syndrome.
AB  - BACKGROUND: FG syndrome (FGS) is an X-linked disorder characterised by mental
      retardation, hypotonia, particular dysmorphic facial features, broad thumbs and
      halluces, anal anomalies, constipation, and abnormalities of the corpus callosum.
      A behavioural phenotype of hyperactivity, affability, and excessive talkativeness
      is very frequent. The spectrum of clinical findings attributed to FGS has widened
      considerably since the initial description of the syndrome by Opitz and Kaveggia
      in 1974 and has resulted in clinical variability and genetic heterogeneity. In
      2007, a recurrent R961W mutation in the MED12 gene at Xq13 was found to cause FGS
      in six families, including the original family described by Opitz and Kaveggia.
      The phenotype was highly consistent in all the R961W positive patients. METHODS:
      In order to determine the prevalence of MED12 mutations in patients clinically
      diagnosed with FGS and to clarify the phenotypic spectrum of FGS, 30 individuals
      diagnosed previously with FGS were evaluated clinically and by MED12 sequencing.
      RESULTS: The R961W mutation was identified in the only patient who had the
      typical phenotype previously associated with this mutation. The remaining 29
      patients displayed a wide variety of features and were shown to be negative for
      mutations in the entire MED12 gene. A definite or possible alternative diagnosis
      was identified in 10 of these patients. CONCLUSION: This report illustrates the
      difficulty in making a clinical diagnosis of FGS given the broad spectrum of
      signs and symptoms that have been attributed to the syndrome. Individuals with a
      phenotype consistent with FGS require a thorough genetic evaluation including
      MED12 mutation analysis. Further genetic testing should be considered in those
      who test negative for a MED12 mutation to search for an alternative diagnosis.

PMID- 18805827
TI  - Mutation in the HPGD gene encoding NAD+ dependent 15-hydroxyprostaglandin
      dehydrogenase underlies isolated congenital nail clubbing (ICNC).
AB  - BACKGROUND: Isolated congenital nail clubbing (ICNC) is a rare autosomal
      recessive disorder characterised by enlargement of the terminal segments of
      fingers and toes with thickened nails due to proliferation of the connective
      tissues and abnormal function of the nail matrix. In the present study, we
      investigated a large Pakistani family with 11 affected individuals having
      hereditary congenital nail clubbing as a single invariable clinical feature
      without any associated ectodermal, skeletal or systemic imperfection. OBJECTIVE:
      To identify a gene underlying the ICNC phenotype. METHODS: A genome wide
      homozygosity linkage mapping strategy was used to identify the gene causing ICNC.
      DNA sequencing was performed to screen 10 candidate genes located in the linkage
      interval. RESULTS: We assigned the disease locus for the ICNC to a 13.25 cM
      region on chromosome 4q32.3-q34.1. This region corresponds to 12.27 Mbp according
      to the sequence based physical map (Build 36.1) and flanked by markers D4S2952
      and D4S415. A maximum two point LOD score of 2.98 ( theta= 0.00) was obtained at
      marker D4S2368 while a maximum multipoint LOD score of 3.62 was obtained with
      several markers along the disease interval. Sequence analysis of the candidate
      genes, in the ICNC linkage interval, revealed a homozygous missense mutation
      (c.577T>C; p.S193P) in exon 6 of the human HPGD gene encoding NAD(+) dependent 15
      hydroxyprostaglandin dehydrogenase (15-PGDH). CONCLUSIONS: The involvement of 15
      PGDH in the pathogenesis of ICNC may open up interesting perspectives into the
      function of this enzyme in nail morphogenesis/development.

PMID- 18805828
TI  - Association of a null allele of SPRN with variant Creutzfeldt-Jakob disease.
AB  - BACKGROUND: No susceptibility genes have been identified in human prion disase,
      apart from the prion protein gene (PRNP). The gene SPRN, encodes Shadoo (Sho,
      shadow of prion protein) which has protein homology and possible functional links
      with the prion protein. METHODS: A genetic screen was carried out of the open
      reading frame of SPRN by direct sequencing in 522 patients with prion disease,
      including 107 with variant Creutzfeldt-Jakob disease (vCJD), and 861 healthy
      controls. RESULTS: A common coding variant of SPRN, two further single nucleotide
      polymorphisms (SNPs) and three rare insertion or deletion variants were found. A
      single base-pair insertion at codon 46, predicted to cause a frameshift and
      potentially a novel protein, was found in two patients with vCJD but not in
      controls (p = 0.01). Two linked SNPs, one in intron 1 and the other a missense
      variant at codon 7, were associated with risk of sporadic CJD (p = 0.009).
      CONCLUSION: These data justify the functional genetic characterisation of SPRN
      and support the involvement of Shadoo in prion pathobiology.

PMID- 18805829
TI  - Site-dependent differences in both prelamin A and adipogenic genes in
      subcutaneous adipose tissue of patients with type 2 familial partial
      lipodystrophy.
AB  - BACKGROUND: Type 2 familial partial lipodystrophy (FPLD2) is characterised by
      loss of fat in the limbs and buttocks and results from mutations in the LMNA
      gene. AIM: To evaluate the role of several genes involved in adipogenesis in
      order to better understand the underlying mechanisms of regional loss of
      subcutaneous adipose tissue (scAT) in patients with FPLD2. METHODS: In total, 7
      patients with FPLD2 and 10 healthy control participants were studied. A minimal
      model was used to calculate the insulin sensitivity (IS). scAT was obtained from
      abdomen and thigh by biopsy. Relative gene expression was quantified by real-time
      reverse transcription PCR in a thermal cycler. Prelamin A western blot analysis
      was carried out on scAT and prelamin A nuclear localisation was determined using
      immunofluorescence. Adipocyte nuclei were examined by electron microscopy.
      RESULTS: Patients with FPLD2 were found to have significantly lower IS. The
      expression of LMNA was similar in both groups. The expression of PPARG2, RB1,
      CCND3 and LPL in thigh but not in abdomen scAT was significantly reduced (67%,
      25%, 38% and 66% respectively) in patients with FPLD2. Significantly higher
      levels of prelamin A were found in peripheral scAT of patients with FPLD2.
      Defects in the peripheral heterochromatin and a nuclear fibrous dense lamina were
      present in the adipocytes of patients with FPLD2. CONCLUSIONS: In FPLD2
      participants, prelamin A accumulation in peripheral scAT is associated with a
      reduced expression of several genes involved in adipogenesis, which could perturb
      the balance between proliferation and differentiation in adipocytes, leading to
      less efficient tissue regeneration.

PMID- 18805830
TI  - Microdeletion/duplication at 15q13.2q13.3 among individuals with features of
      autism and other neuropsychiatric disorders.
AB  - BACKGROUND: Segmental duplications at breakpoints (BP4-BP5) of chromosome
      15q13.2q13.3 mediate a recurrent genomic imbalance syndrome associated with
      mental retardation, epilepsy, and/or electroencephalogram (EEG) abnormalities.
      PATIENTS: DNA samples from 1445 unrelated patients submitted consecutively for
      clinical array comparative genomic hybridisation (CGH) testing at Children's
      Hospital Boston and DNA samples from 1441 individuals with autism from 751
      families in the Autism Genetic Resource Exchange (AGRE) repository. RESULTS: We
      report the clinical features of five patients with a BP4-BP5 deletion, three with
      a BP4-BP5 duplication, and two with an overlapping but smaller duplication
      identified by whole genome high resolution oligonucleotide array CGH. These BP4
      BP5 deletion cases exhibit minor dysmorphic features, significant expressive
      language deficits, and a spectrum of neuropsychiatric impairments that include
      autism spectrum disorder, attention deficit hyperactivity disorder, anxiety
      disorder, and mood disorder. Cognitive impairment varied from moderate mental
      retardation to normal IQ with learning disability. BP4-BP5 covers approximately
      1.5 Mb (chr15:28.719-30.298 Mb) and includes six reference genes and 1 miRNA
      gene, while the smaller duplications cover approximately 500 kb (chr15:28.902
      29.404 Mb) and contain three reference genes and one miRNA gene. The BP4-BP5
      deletion and duplication events span CHRNA7, a candidate gene for seizures.
      However, none of these individuals reported here have epilepsy, although two have
      an abnormal EEG. CONCLUSIONS: The phenotype of chromosome 15q13.2q13.3 BP4-BP5
      microdeletion/duplication syndrome may include features of autism spectrum
      disorder, a variety of neuropsychiatric disorders, and cognitive impairment.
      Recognition of this broader phenotype has implications for clinical diagnostic
      testing and efforts to understand the underlying aetiology of this syndrome.

PMID- 18805831
TI  - Schimke immuno-osseous dysplasia: SMARCAL1 loss-of-function and phenotypic
      correlation.
AB  - BACKGROUND: Schimke immuno-osseous dysplasia (SIOD) is an autosomal recessive
      pleiotropic disorder caused by mutations in SMARCAL1. SMARCAL1 encodes an enzyme
      with homology to the SNF2 chromatin remodelling proteins. METHODS: To assess the
      affect of SMARCAL1 mutations associated with SIOD on SMARCAL1 expression and
      function, we characterised the effects of various mutations on mRNA and protein
      expression in patient tissues and cell lines, and the ATPase activity,
      subcellular localisation, and chromatin binding of SMARCAL1 missense mutants.
      RESULTS: The SIOD associated SMARCAL1 mutations affected SMARCAL1 protein
      expression, stability, subcellular localisation, chromatin binding, and enzymatic
      activity. Further, expressing SMARCAL1 missense mutants in Drosophila
      melanogaster showed that disease severity was inversely proportionate to overall
      SMARCAL1 activity. CONCLUSION: Our results show for the first time that SMARCAL1
      binds chromatin in vivo and that SIOD arises from impairment of diverse SMARCAL1
      functions.

PMID- 18805832
TI  - Germany's plans to reduce use of tobacco and alcohol provoke protests from
      industry and local politicians.

PMID- 18805833
TI  - Law might change to protect people who have computed tomography.

PMID- 18805834
TI  - Doctors should be alert for virulent community acquired Staphylococcus aureus
      infection.

PMID- 18805835
TI  - Diagnostic evaluation of people with hypertension in low income country: cohort
      study of "essential" method of risk stratification.
AB  - OBJECTIVES: To explore the predictive power of a risk stratification method for
      people with hypertension based on "essential" procedures (that is, available in
      economically less developed areas of the world), comparing it in the same
      population with the results given by the method suggested by the 1999 World
      Health Organization-International Society of Hypertension (WHO-ISH) guidelines.
      DESIGN: Prospective cohort study of outcomes according to cardiovascular risk
      profile at baseline. SETTING: Primary care in a poor rural area of the Ecuadorian
      forest. PARTICIPANTS: 504 people with hypertension prospectively monitored for a
      mean of 6.7 (SD 2.3) years. INTERVENTIONS: Essential data included blood
      pressure, medical history, smoking, age, sex, and diagnosis of diabetes; the WHO
      ISH methods additionally included measurement of fasting blood glucose, total
      cholesterol, and creatinine, urinalysis, and electrocardiography. MAIN OUTCOME
      MEASURES: Cardiovascular events and total deaths. RESULTS: With both methods
      there was a highly significant association between the level of predicted risk
      and the incidence of cardiovascular events and of total deaths: up to three
      quarters of all cardiovascular events and two thirds of all deaths were reported
      among people classified as at high or very high risk with either method. The
      predictive discrimination of the essential method is comparable with the WHO-ISH
      with C statistics (95% confidence interval) of 0.788 (0.721 to 0.855) and 0.744
      (0.673 to 0.815), respectively, for cardiovascular events and 0.747 (0.678 to
      0.816) and 0.705 (0.632 to 0.778) for total mortality. CONCLUSIONS: The risk
      stratification of patients with hypertension with an essential package of
      variables (that is, available and practicable even in the economically less
      developed areas of the world) serves at least as well as the more comprehensive
      method proposed by WHO-ISH.

PMID- 18805837
TI  - Interferon-beta bioactivity measurement in multiple sclerosis: feasibility for
      routine clinical practice.
AB  - BACKGROUND: Neutralising antibodies (NAb) to interferon beta (IFN beta) are
      associated with a reduced bioactivity and efficacy of IFN beta in multiple
      sclerosis (MS). Unclear is how to apply IFN beta bioactivity measurements
      (quantification of Myxovirus resistance protein A (MxA) mRNA) in clinical
      practice. OBJECTIVES: To evaluate value and feasibility of IFN beta bioactivity
      measurement with a single MxA mRNA measurement for screening and a second
      measurement before and after IFN beta administration for definite confirmation of
      IFN beta bioactivity status. METHODS: In 79 MS patients MxA mRNA expression was
      determined 4 hours after IFN beta administration. If inadequate, MxA mRNA
      expression testing was repeated 3 months afterwards, comparing post- and pre
      injection samples to determine whether IFNb bioactivity was persistently lacking.
      MxA mRNA expression was compared to NA beta titres, determined by the cytopathic
      effect assay (CPE). RESULTS: NAb titres correlated significantly with MxA mRNA
      expression and MxA mRNA induction. Of all screened patients, only one patient had
      adequate MxA mRNA expression and high NAb titres simultaneously. Of the
      biological non-responders at second measurement (21/55), 17 (81%) were high-titre
      NAb positive, 1 (5%) was low-titre NAb positive and 3 (14%) were NAb negative.
      Without considering the pre-injection measurement, two more NAb negative patients
      would have tested negative for IFN beta bioactivity, emphasizing the need of a
      pre-injection sample. CONCLUSIONS: Our data suggest that for IFN beta bioactivity
      screening a single post-injection measurement seems reasonable. However, MxA
      induction measurement based on both pre- and post-IFN beta injection samples at
      second measurement is somewhat more precise in determining ultimate IFN beta
      bioactivity status.

PMID- 18805838
TI  - An APOA1 promoter polymorphism is associated with cognitive performance in
      patients with multiple sclerosis.
AB  - BACKGROUND: Elevated ApoA1 levels have been associated with decreased dementia
      risk. The A-allele of the APOA1 -75G/A promoter polymorphism has been associated
      with elevated ApoA1 levels. OBJECTIVE: We sought to investigate the effect of the
      APOA1 -75G/A promoter polymorphism on cognitive performance in patients with
      multiple sclerosis (MS). METHODS: A total of 138 patients with MS and 43 controls
      were studied and underwent neuropsychological assessment with Rao's Brief
      Repeatable Battery and the Stroop test. All patients were genotyped for APOA1.
      RESULTS: APOA1 A-allele carriers displayed superior overall cognitive performance
      compared with non-carriers (P 0.008) and had a three-fold decrease in the
      relative risk of overall cognitive impairment (OR 0.29, 95% CI 0.11-0.74).
      Regarding performance on individual cognitive domains, although APOA1 A-allele
      carriers performed better than non-carriers on all tests, this was significant
      only for semantic verbal fluency and the Stroop interference task (P 0.036 and
      0.018, respectively). CONCLUSIONS: We found an association of the APOA1 -75G/A
      promoter polymorphism with cognitive performance in MS. This effect was most
      prominent on semantic verbal fluency and the Stroop interference task.

PMID- 18805839
TI  - Differential diagnosis of suspected multiple sclerosis: a consensus approach.
AB  - BACKGROUND AND OBJECTIVES: Diagnosis of multiple sclerosis (MS) requires
      exclusion of diseases that could better explain the clinical and paraclinical
      findings. A systematic process for exclusion of alternative diagnoses has not
      been defined. An International Panel of MS experts developed consensus
      perspectives on MS differential diagnosis. METHODS: Using available literature
      and consensus, we developed guidelines for MS differential diagnosis, focusing on
      exclusion of potential MS mimics, diagnosis of common initial isolated clinical
      syndromes, and differentiating between MS and non-MS idiopathic inflammatory
      demyelinating diseases. RESULTS: We present recommendations for 1) clinical and
      paraclinical red flags suggesting alternative diagnoses to MS; 2) more precise
      definition of "clinically isolated syndromes" (CIS), often the first
      presentations of MS or its alternatives; 3) algorithms for diagnosis of three
      common CISs related to MS in the optic nerves, brainstem, and spinal cord; and 4)
      a classification scheme and diagnosis criteria for idiopathic inflammatory
      demyelinating disorders of the central nervous system. CONCLUSIONS: Differential
      diagnosis leading to MS or alternatives is complex and a strong evidence base is
      lacking. Consensus-determined guidelines provide a practical path for diagnosis
      and will be useful for the non-MS specialist neurologist. Recommendations are
      made for future research to validate and support these guidelines. Guidance on
      the differential diagnosis process when MS is under consideration will enhance
      diagnostic accuracy and precision.

PMID- 18805840
TI  - Analysis of cerebrospinal fluid and cerebrospinal fluid cells from patients with
      multiple sclerosis for detection of JC virus DNA.
AB  - OBJECTIVE: 1) To determine whether JC virus (JCV) DNA was present in the
      cerebrospinal fluid (CSF) and blood from patients with multiple sclerosis (MS) in
      comparison with controls and 2) to find out if our clinical material, based on
      presence of JCV DNA, included any patient at risk for progressive multifocal
      leukoencephalopathy (PML). METHODS: The prevalence of JCV DNA was analyzed in CSF
      and plasma from 217 patients with MS, 86 patients with clinically isolated
      syndrome (CIS), and 212 patients with other neurological diseases (OND). In
      addition, we analyzed CSF cells, the first report of JCV DNA in CSF cells in a
      single sample, and peripheral blood cells in a subgroup of MS (n = 49), CIS (n =
      14) and OND (n = 53). RESULTS: A low copy number of JCV DNA was detected in one
      MS cell free CSF sample and in one MS CSF cell samples. None of these had any
      signs of PML or developed this disease during follow-up. In addition, two OND
      plasma samples were JCV DNA positive, whereas all the other samples had no
      detectable virus. CONCLUSION: A low copy number of JCV DNA may occasionally be
      observed both in MS and other diseases and may occur as part of the normal
      biology of JC virus in humans. This study does not support the hypothesis that
      patients with MS would be at increased risk to develop PML, and consequently
      screening of CSF as a measurable risk for PML is not useful.

PMID- 18805841
TI  - Early highly aggressive MS successfully treated by hematopoietic stem cell
      transplantation.
AB  - BACKGROUND: During the last 15 years, high-dose chemotherapy with autologous
      hematopoietic stem cell transplantation (HSCT) has globally been performed for
      severe multiple sclerosis (MS). Most patients have been in progressive phase with
      long disease duration. As a rule, treatment effect has been minor or moderate.
      PATIENTS: Since 2004, we have performed HSCT in nine young patients with
      "malignant" relapsing-remitting MS. Criteria for treatment were short duration of
      disease; very frequent, severe relapses; recent improvement periods indicating
      potential for recovery after strong immunosuppression. FINDINGS: Median age at
      treatment was 27 (range 9-34) years, MS duration 26 (4-100) months, and
      annualized relapse rate 10 (4-12). Median Disability Status Scale (extended
      disability status scale, EDSS) at HSCT was 7.0 (3.5-8.0). Median follow-up time
      April 2008 is 29 (23-47) months. Median EDSS improvement is 3.5 (1.0-7.0),
      clearly surpassing most previous reports. One patient relapsed mildly with rapid
      recovery 7 months after HSCT. All patients are otherwise stable, median EDSS
      being 2.0 (0-6.0). Before HSCT, 61 relapses occurred in 82 patient months; during
      follow-up, one relapse in 289 patient months. CONCLUSION: This small series of
      patients with "malignant" relapsing-remitting MS suggests HSCT to be an effective
      treatment option for this relatively rare disease course. It further suggests
      that future criteria for HSCT in MS should be close to the present ones.

PMID- 18805842
TI  - Cognitive impairment in multiple sclerosis.
AB  - BACKGROUND: Cognitive impairment is increasingly being recognized as a common and
      disabling symptom of multiple sclerosis (MS) that contributes to poor quality of
      life in affected patients. Despite the high prevalence of cognitive impairment in
      MS, cognitive function is not assessed routinely in clinical practice or in
      clinical trials. The perception that cognitive assessments are costly, time
      consuming, complicated, and difficult to administer and interpret has
      contributed, at least in part, to the failure to incorporate cognitive testing
      into standard clinical evaluation of patients with MS. Detailed studies of
      cognitive impairment in MS are rare and guidelines for the assessment of
      cognitive function in MS are lacking. TREATMENT: How to manage cognitive decline
      in MS also requires further study. Licensed disease-modifying drug (DMD)
      treatments for MS reduce brain lesion development, and associations between brain
      lesions and cognitive performance have been reported, providing a rationale for
      DMD treatment of MS-associated cognitive impairment. There is some evidence for
      cognitive benefits of DMDs, but as few pivotal DMD trials included cognitive
      assessments, the effects of these agents on cognition are not fully understood
      and more studies are needed. CONCLUSIONS: It is only through further studies that
      it will be possible to identify patients with, or at risk of, cognitive
      impairment and to provide appropriate therapy to limit the effects of this
      potentially devastating symptom.

PMID- 18805843
TI  - Autoimmune disease in patients with multiple sclerosis and their first-degree
      relatives: a nationwide cohort study in Denmark.

PMID- 18805844
TI  - CNS demyelination and quadrivalent HPV vaccination.
AB  - Vaccination is generally considered safe in patients with multiple sclerosis
      (MS). We report five patients who presented with multifocal or atypical
      demyelinating syndromes within 21 days of immunization with the quadrivalent
      human papilloma virus (HPV) vaccine, Gardasil. Although the target population for
      vaccination, young females, has an inherently high risk for MS, the temporal
      association with demyelinating events in these cases may be explained by the
      potent immuno-stimulatory properties of HPV virus-like particles which comprise
      the vaccine. A prospective case-control study of patients with MS or clinically
      isolated demyelinating syndromes receiving the Gardasil vaccine may provide
      relevant safety data in this population.

PMID- 18805845
TI  - Potential side effect of high-dose corticosteroid relapse treatment: acute
      generalized exanthematous pustulosis (AGEP).
AB  - INTRODUCTION: High-dose glucocorticosteroids (GC) are the treatment of choice for
      acute relapses in patients with multiple sclerosis as proven by several
      controlled clinical trials. The common adverse effects of GC are well known. CASE
      PRESENTATION: In this study, we report on the exceptional case of a young female
      treated with intravenous high-dose prednisolone for optic neuritis who developed
      acute generalized exanthematous pustulosis (AGEP). AGEP is a rare cutaneous
      adverse reaction induced most frequently by antimicrobial or antihypertensive
      drugs and viral infections. It is characterized by a febrile erythematous and
      pustular rash and blood granulocytosis. CONCLUSION: In our patient, switching to
      dexamethasone for the next relapse was tolerated well and is an option for
      treatment. AGEP is a rare adverse effect of corticosteroid treatment.

PMID- 18805846
TI  - Utility of the PFA-100 instrument and the novel multiplate analyzer for the
      assessment of aspirin and clopidogrel effects on platelet function in patients
      with cardiovascular disease.
AB  - This study evaluated the utility of the PFA-100 and the Multiplate analyzer for
      the assessment of aspirin and clopidogrel effects on platelet function in
      patients with cardiovascular disease. Platelet function was determined with the
      PFA-100 using collagen+epinephrine (CEPI) and collagen+adenosine-5'-diphosphate
      (CADP) cartridges, and with whole blood impedance aggregometry using the
      Multiplate ASPI and ADP+PG tests (aggregation triggered with arachidonic acid and
      ADP+ prostaglandin E1, respectively). Four study groups were identified from the
      154 patients enrolled: patients without antiplatelet therapy, patients with 100
      mg aspirin daily but without clopidogrel treatment, patients with 75 mg
      clopidogrel daily but without aspirin treatment, and patients with both 100 mg
      aspirin daily plus 75 mg clopidogrel daily. It was found that the PFA-100
      instrument is useful for detection of aspirin but not for detection of a
      clopidogrel effect, while the Multiplate analyzer is useful for specific
      detection of both aspirin and clopidogrel effects on platelet function.

PMID- 18805847
TI  - Quantitative PCR and disaccharide profiling to characterize the animal origin of
      low-molecular-weight heparins.
AB  - Low-molecular-weight heparins (LMWHs) are widely used in the management of
      thrombosis and acute coronary syndromes. They are obtained by the enzymatic or
      chemical depolymerization of porcine intestinal heparin. Enoxaparin sodium, a
      widely used LMWH, has a unique and reproducible oligosaccharide profile which is
      determined by the origin of the starting material and a tightly controlled
      manufacturing process. Although other enoxaparin-like LMWHs do exist, specific
      release criteria including the origin of the crude heparin utilized for their
      production, have not been established. A quantitative polymerase chain reaction
      method has been developed to ensure the purity of the porcine origin of crude
      heparin, with a DNA detection limit as low as 1 ppm for bovine, or 10 ppm for
      ovine contaminants. This method is routinely used as the release acceptance
      criterion during enoxaparin sodium manufacturing. Furthermore, when the process
      removes DNA, other analytical techniques can be used to assess any contamination.
      Disaccharide profiling after exhaustive depolymerization can determine the
      presence of at least 10% bovine or 20% ovine material; multivariate analysis is
      useful to perform the data analysis. Consistent with the availability of newer
      technology, these methods should be required as acceptance criteria for crude
      heparins used in the manufacture of LMWHs to ensure their safety, quality, and
      immunologic profile.

PMID- 18805848
TI  - Metrics that matter: can transparency fix the health care system?

PMID- 18805849
TI  - Improving quality of care in cardiac surgery: evaluating risk factors, processes
      of care, structures of care, and outcomes.
AB  - The 1985 release of hospital report cards by the Health Care Financing
      Administration awakened the public's awareness of variations in outcomes
      following patient treatment. In 1972, the Department of Veterans Affairs
      initiated an oversight process for all VA-based cardiac surgery programs. In
      response to Public Law 99-166, the Continuous Improvement in Cardiac Surgery
      Program (CICSP) national database was developed in 1987. This CICSP effort
      reported variations in outcomes across VA cardiac programs. In 1997, the CICSP
      expanded (CICSP-X) to identify the interrelationships of risk factors with
      processes and structures of care, as well as clinical outcomes. Based on VA
      findings to date, these quality improvement endeavors appear to have positively
      affected short-term and longer-term cardiac surgical outcomes. To advance a new
      patient-focused paradigm for continuous improvement in cardiac surgical care
      quality for all US citizens, an integrated data-driven reporting approach with
      broad-based participation should be implemented to optimally improve patient
      care.

PMID- 18805850
TI  - An introduction to statistical methods used in binary outcome modeling.
AB  - Logistic regression is a cornerstone of epidemiology and the method of choice for
      risk adjustment models in cardiac surgery and critical care. Although linear
      regression methods may be satisfactory to evaluate relationships between
      independent (predictor) variables and a outcome that is continuous, a more
      complex mathematical approach is required when the outcome is binary (yes/no;
      alive/dead). Although the odds are 4 to 1 that finding an antilogarithm may sound
      intimidating, once you get past the initial equations and terminology, we go on
      to discuss how to select variables for a model, how to deal with collinearity and
      interaction terms, how to use diagnostic tests to ensure the model is not
      adversely affected by a small number of observations, and how to assess a model's
      discrimination and calibration. A full understanding of how logistic models are
      developed is useful when assessing the medical literature on risk assessment.

PMID- 18805851
TI  - Risk stratification models for cardiac surgery.
AB  - A wide variety of risk stratification systems have been developed to quantify the
      risk of cardiac surgery. Generally, the focus has been on mortality; however,
      more recently models have been developed that allow the preoperative prediction
      of the incidence of morbidity, including renal failure, infection, prolonged
      ventilation, and neurologic deficit. Many of these risk stratification models are
      developed from large databases of cardiac surgical patients. Patient and surgical
      factors that are present preoperatively are assessed for their predictive value
      for postoperative complications. Risk factors that are found to be significant
      are assigned a specific weight in the overall summation of risk. These models
      have been used as tools to compare surgeon's results, institutional outcomes,
      individual patient risk, and within quality improvement programs. This article
      will focus on the European System for Cardiac Operative Risk Evaluation, the
      Society of Thoracic Surgeons score, the Parsonnet score, Cleveland Clinic Model,
      the Bayes model, and the Northern New England Score.

PMID- 18805852
TI  - Predicting outcomes for cardiac surgery patients after intensive care unit
      admission.
AB  - Most performance assessments of cardiac surgery programs use models based on
      preoperative risk factors. Models that were primarily developed to assess
      performance in general intensive care unit (ICU) populations have also been used
      to evaluate the quality of surgical, anesthetic, and ICU management after cardiac
      surgery. Although there are currently 5 models for evaluating general ICU
      populations, only the Acute Physiology and Chronic Health Evaluation (APACHE)
      system has been independently validated for cardiac surgery patients. This review
      describes the evolution, rationale, and accuracy of APACHE models that are
      specific for cardiac surgery patients as well as for patients who have had
      vascular and thoracic procedures. In addition to performance comparisons based on
      observed and predicted mortality, APACHE provides similar comparisons of ICU and
      hospital lengths of stay and duration of mechanical ventilation. However, the low
      mortality incidence of many cardiac outcomes means that very large numbers of
      patients must be obtained to get good predictive models. Thus, the equations are
      not designed for predicting individual patients' outcome but have proven useful
      in performance comparisons and for quality improvement initiatives.

PMID- 18805853
TI  - Perception and reporting of cardiac surgical performance.
AB  - The high level of interest in surgical outcomes has led to the publication of
      mortality rates in the public domain. In cardiac surgery, the availability of
      quite sophisticated risk assessment has allowed these outcomes to be adjusted for
      risk. The European System for Cardiac Operative Risk Evaluation is a widely
      recognized and used risk scoring system and has been used and validated
      throughout Europe and beyond. The logistic version is now the most commonly
      applied, but recalibration may be required. The methodology and statistics for
      measuring risk-adjusted performance are available, and regular audit and
      performance monitoring should be carried out in all cardiac surgical units. In
      the United Kingdom, risk-adjusted outcomes are available and regularly updated on
      the Internet. Presentation of data may be improved by the use of variable life
      adjusted display curves. League tables for crude mortality can be misleading and
      should be avoided. When properly conducted, the measurement of risk-adjusted
      surgical outcomes should improve quality control and decision making and allow
      early identification of poor performance. Quality monitoring in medicine is a
      priority, and similar methods can be employed in other specialties, including
      anesthesia, by establishing and analyzing risk-stratified outcome data sets.

PMID- 18805854
TI  - Public health reporting: the United States perspective.
AB  - The release of 2 landmark reports by the Institute of Medicine titled, "To Err Is
      Human: Building a Safer Health System" and "Crossing the Quality Chasm" were
      instrumental in the identification of safety and quality issues. Since their
      release, federal and state programs of public reporting of performance measures
      have attempted to close the quality gap of care that is inappropriate, not
      timely, or lacking an evidence base. Cardiac surgery has long been the focus of
      public scrutiny, and now, as we move from an era of managed care to public
      reporting, reimbursement for cardiac surgery procedures will be tied to
      performance. However, the question is whether public reporting and pay for
      performance will ultimately improve the quality of patient care, safety, and
      provide the consumer with enough information to make surgeon and institutional
      choices. Will the cost and focus of achieving perfection with performance
      standards overshadow any real improvement in clinical outcomes?

PMID- 18805855
TI  - Health-related quality of life after cardiac surgery.
AB  - Health-related quality of life (HRQOL) assessments are designed to reflect a
      patient's perspective of how a disease has affected their overall health status.
      Patient-centered outcomes are of value both for risk assessment and as an outcome
      measure. Strategies for analyzing HRQOL data are inconsistent primarily because
      the data frequently do not meet underlying assumptions of traditional methods for
      statistical analyses and require a careful analytic approach.

PMID- 18805856
TI  - Hemodynamic effects and safety of nesiritide in neonates with heart failure.
AB  - OBJECTIVE: Evaluate effects and safety of nesiritide (Natrecor, Scios Inc.) human
      B-type natriuretic peptide, in neonates with heart failure. METHODS: Seventeen
      neonates, not responding to conventional therapy, treated with nesiritide were
      retrospectively reviewed. RESULTS: Average age 16 + 8 days; weight 3.2 + 0.6 kg.
      Fifteen treated with concomitant inotropic therapy; all with diuretics. Twelve
      received loading dose; followed by continuous infusions of 0.005 mcg/kg/min (2);
      0.01 mcg/kg/min (12); 0.02 mcg/kg/min (3). Length of therapy 5 + 4 days. No
      change in heart rate or blood pressure between baseline, 1 hour or 24 hours of
      nesiritide infusion. Decrease central venous pressure (CVP) 24 hours after
      infusion (p = 0.03). Ins-out ratio improved in 29%. No difference in pre and post
      therapy BUN and creatinine (Cr). 18% had hypotension requiring intervention.
      CONCLUSIONS: Nesiritide use in neonates may improve hemodynamics as demonstrated
      by reduction in CVP. All patients tolerated bolus dosing, however, transient
      hypotension occurred in 18% of neonates with continuous infusion.

PMID- 18805857
TI  - Review of a large clinical series: sedation and analgesia usage with airway
      pressure release and assist-control ventilation for acute lung injury.
AB  - BACKGROUND: Our objective was to compare sedative and analgesic doses, agents,
      and sedation status in patients with airway pressure release ventilation (APRV)
      versus assist-control (AC) ventilation on the first day after acute lung injury
      diagnosis. METHODS: Observational study at 3 teaching hospitals. RESULTS: Of 240
      patients, 165 received APRV or AC ventilation on day 1 (17 APRV, 148 AC). The
      median Acute Physiology and Chronic Health Evaluation II score was lower in the
      APRV versus AC group [17 (14-20) vs. 25 (21-32), P < .001]. Median total doses of
      sedatives and analgesics were lower in APRV versus AC (29 vs. 98 mg of midazolam
      equivalents, P < .001) and (1200 vs. 2400 mcg of fentanyl equivalents, P = .006).
      APRV patients were less sedated versus AC (median Richmond Agitation-Sedation
      Scale -2 vs. -4, P < .002). CONCLUSIONS: APRV may be associated with decreased
      sedation and analgesia medications and improved sedation status. Differences in
      the patients receiving APRV versus AC ventilation may have contributed to this
      conclusion. Further investigation is needed.

PMID- 18805858
TI  - Use of drotrecogin alfa in necrotizing fasciitis: a case report and pharmacologic
      review.
AB  - Necrotizing fasciitis (NF) is a devastating subset of necrotizing soft tissue
      infections that requires prompt diagnosis and treatment. Although often occurring
      in patients with impaired host defense mechanisms (diabetes mellitus, systemic
      immunosuppression, malignancy, etc.), NF may also present in the immunocompetent
      following a cutaneous lesion or break. Patients with NF often progress to a
      systemic inflammatory response syndrome or multiorgan system failure that demands
      advanced critical care practices. We present a case of NF in an immunocompetent
      patient and the subsequent use of drotrecogin alfa (Xigris). A review of the
      pharmacologic treatment of streptococcal NF is included. The addition of
      drotrecogin alfa to operative debridement and penicillin G/clindamycin therapy
      may be a useful adjunct in the treatment of necrotizing fasciitis due to group A
      streptococcus.

PMID- 18805859
TI  - Donation after cardiac death: perceptions versus reality.

PMID- 18805861
TI  - Anion gap, anion gap corrected for albumin, and base deficit fail to accurately
      diagnose clinically significant hyperlactatemia in critically ill patients.

PMID- 18805862
TI  - Effects of hypoxic and hyperoxic incubation on the reactivity of the chicken
      embryo (Gallus gallus) ductus arteriosi in response to catecholamines and oxygen.
AB  - Development in chronic hypoxia has been shown to have a significant negative
      impact on the developing cardiovascular system. The developing chicken embryo has
      two ductus arteriosi (DA) that shunt blood away from the lungs to the systemic
      circuit and constrict during hatching in response to an increase in arterial
      partial pressure of O(2). The goal of this study was to determine the influence
      of O(2) levels during incubation on the vascular reactivity of the O(2)-sensitive
      DA using the chicken as a novel model system. In addition, we measured blood gas
      and air cell O(2) during these developmental stages. Chicken embryos were
      incubated in hypoxia (15% O(2)), normoxia (21% O(2)) or hyperoxia (30% O(2)) and
      examined on incubation days 16 and 18 and as internally pipped and externally
      pipped embryos. The vasoreactivity of the DA was measured in response to an
      increase in O(2) and during stepwise increases in noradrenaline (NA) and
      phenylephrine (PE). The DA from embryos incubated in hypoxic conditions
      contracted in response to O(2) at a later hatching stage than the DA from embryos
      incubated in normoxic or hyperoxic conditions. The DA from day 18 embryos
      incubated in hypoxic conditions had a significantly weaker contractile response
      to NA and PE when compared with the DA from embryos incubated in normoxic or
      hyperoxic conditions. Blood gas and air cell O(2) were lowest for embryos
      incubated in hypoxic conditions and highest for embryos incubated in hyperoxic
      conditions. Incubation in hypoxia significantly delays the maturation of DA,
      while incubation in hyperoxia accelerates development.

PMID- 18805863
TI  - Neuroeffector Ca2+ transients for the direct measurement of purine release and
      indirect measurement of cotransmitters in rodents.
AB  - Determining whether ATP and noradrenaline are released from the same vesicle at
      mature autonomic neuroeffector junctions is challenging because of the difficulty
      of simultaneously detecting the packeted release of these neurotransmitters.
      Contraction, overflow and electrophysiology experiments all show that both ATP
      and noradrenaline are released following field stimulation (although the ratio
      might vary) from autonomic nerves in tissues including the vas deferens, rat tail
      artery and mesenteric artery. The occurrence of purinergic neuroeffector Ca(2+)
      transients (NCTs) has been used to detect the packeted release of the
      neurotransmitter ATP acting on postjunctional P2X receptors to cause Ca(2+)
      influx. Neuroeffector Ca(2+) transients can also be used to detect the local
      effects of noradrenaline through its alpha(2)-adrenoceptor-mediated prejunctional
      autoinhibitory effects on nerve terminal Ca(2+) concentration and the probability
      of exocytosis (measured by counting NCTs). Evidence is presented that exocytosis
      from sympathetic varicosities does not occur in a manner independent of the
      history of that varicosity, but rather that the release of a packet of ATP
      transiently suppresses (or predicts the transient suppression of) subsequent
      release. This could arise by autoinhibition (by the prejunctional action of
      noradrenaline or purines) or due to a transient shortage of vesicles readily
      available for release. In summary, two high-resolution approaches are proposed to
      measure the intermittent release of packets of neurotransmitter: (1) local
      transient suppression of nerve terminal Ca(2+) transients; and (2) the local and
      transient inhibition of NCTs to infer local autoinhibition, hence transmitter
      release. Such approaches may allow the packeted corelease of ATP and
      noradrenaline to be investigated without the need to measure both
      neurotransmitters directly.

PMID- 18805864
TI  - The ageing endothelium, cardiovascular risk and disease in man.
AB  - Ageing is a major risk factor for cardiovascular disease, not only because there
      is a process of vascular ageing per se but also because ageing increases the time
      of exposure to other cardiovascular risk factors. Endothelial dysfunction is now
      considered an early and important mechanism that predisposes to atherothrombotic
      damage and thus contributes to the occurrence of cardiovascular events. The
      normal endothelium exerts a major vascular-protecting role by secreting
      substances, the most important of which is nitric oxide (NO). In disease
      conditions (such as the presence of cardiovascular risk factors), activation of
      endothelial cells can lead to the production and release of contracting factors,
      which counteract the beneficial effects of NO, and reactive oxygen species (ROS),
      which cause NO breakdown. Besides the opposite effects on vascular tone, NO and
      endothelium-derived contracting factors also respectively inhibit and activate
      several other mechanisms that are involved in the pathogenesis of
      atherothrombosis. Moreover, endothelial dysfunction is associated with vascular
      subclinical damage and, importantly, an increasing body of evidence strongly
      suggests that it might be an independent predictor for the risk of future
      cardiovascular events. Like the other traditional risk factors, ageing has been
      demonstrated to be associated with progressive impairment of endothelial
      function, in both conduit arteries and resistance vessels, mainly because of an
      increased production of ROS. Therefore, it is conceivable that endothelial
      dysfunction plays a major role in predisposing to age-related increased
      cardiovascular risk in the elderly.

PMID- 18805865
TI  - Patient perception of medicare fee schedule of laparoscopic procedures.
AB  - INTRODUCTION: It seems that public perception is that physicians receive
      substantial payments for procedures. This investigation explores patient
      perception and opinion of Medicare reimbursements to surgeons related to
      laparoscopic surgery. Our hypothesis was that patients think the surgeon Medicare
      fee schedule is higher than actuality. METHODS: Patients filled out an IRB
      exempted survey. The survey included a written description of laparoscopic
      gastric bypass, laparoscopic adjustable gastric band placement, laparoscopic
      cholecystectomy and an initial patient visit for 30 minutes. All participants
      were asked to give their thoughts of what Medicare currently reimburses for these
      procedures as well as what the payment should be. The survey also asked other
      questions about reimbursement related to Medicare. RESULTS: There were 96
      participants in the investigation with 43% of patients not filling in
      reimbursements for at least one procedure. Most patients (88%) looked at their
      bills from physicians and insurance companies carefully. For each procedure, the
      mean reimbursements were approximately 10 times higher than the patient
      perception of both the amount Medicare currently pays and the amount Medicare
      should pay compared to the actual fee. For the initial patient visit, the
      patients overestimated the payment by 158% and thought the Medicare should pay
      199% of the actual fee. Most of the patients (98%) thought Medicare should pay
      more for more difficult cases and 85% thought Medicare should pay more if the
      patient visits the surgeon more times during the global period. While 32% of the
      patients feel Medicare pay physicians well, 91% thought that Medicare should
      increase fees. CONCLUSION: Most of our patients overestimated what Medicare
      currently pays for some laparoscopic procedures. Surgeons need to do a better job
      in educating patients and the general public about the Medicare fee schedule.

PMID- 18805866
TI  - Anatomy of NOTES gastrotomy in human tissue.
AB  - BACKGROUND: Transoral natural orifice translumenal endoscopic surgery (NOTES)
      procedural success depends on a secure gastrotomy closure. Balloon gastrotomy is
      the most common technique to date, but the stomach-layer defect sizes and their
      relationship in human tissue has not been determined. METHODS: Ten 2-cm diameter
      controlled radial expansion balloon gastrotomies were performed in ex vivo human
      tissue. All gastrotomies were located on the anterior stomach wall. The main axis
      of the elliptical-shaped serosal and longitudinal muscle layer opening, the
      mucosal opening, and the circular muscle layer opening (after removal of mucosa)
      was measured. All steps were photo documented and electronically analyzed for
      common opening size. RESULTS: The average common opening was 1 +/- 0.6 to 1.3 cm,
      although the main axis of a single layer can be as long as 2.2 cm. The average
      serosal/longitudinal muscle layer defect measured 1.5 cm, the average mucosal
      defect 1.6 cm, and the average circular muscle layer defect 1.5 cm. CONCLUSION:
      These findings on NOTES gastrotomy anatomy demonstrate the complexity of the
      stomach wall opening and the challenge of providing a fail-safe gastrotomy
      closure. Further in vivo human studies are advised.

PMID- 18805867
TI  - Single port sigmoidectomy in an experimental model with survival.
AB  - INTRODUCTION: Single port laparoscopic access could reduce morbidity associated
      with additional trocar placement and, through the development of a hybrid
      intermediate, facilitate the clinical adoption of evolving techniques such as
      natural orifice transluminal endoscopic surgery. Advanced trocar technology, as
      much as adapted surgical technique, seems necessary to best facilitate this,
      however. METHODS: A novel port (Airseal, Surgiquest) that uses vortex technology
      to create an air-curtain seal to maintain the pneumoperitoneum while facilitating
      the simultaneous passage of multiple working instruments was trialed. For this, 6
      pigs (30 kg each) underwent sigmoid resection and reanastomosis using the port as
      the sole laparoscopic access for conventional instrumentation. All animals were
      thereafter survived for observation during a 2-week convalescence before
      undergoing repeat general anesthesia, sigmoidoscopy for anastomotic assessment,
      and forensic laparotomy for determination of intraperitoneal healing and
      complications. RESULTS: The operation was technically feasible via a single port
      within a short time in every animal (mean duration 12.3 minutes). One anastomosis
      had to redone because of staple misfire but this too was accomplishable without
      additional port placement. All animals survived and convalesced normally without
      evincing clinical complication. At follow-up, all anastomoses were patent at
      sigmoidoscopy and only 1 animal had evidence of complicated anastomotic healing
      (the same animal that had needed anastomotic refashioning). CONCLUSIONS: Single
      port colonic resection and reanastomosis is readily achievable in this animal
      model. As an operative approach, it may both advance in its own right as much as
      facilitate the evolution and clinical incorporation of other developmental access
      routes.

PMID- 18805868
TI  - Papillary hemangiomas and glomeruloid hemangiomas are distinct
      clinicopathological entities.
AB  - The author reviews and compares the clinicopathological features of papillary
      hemangiomas and glomeruloid hemangiomas, 2 rare, cutaneous intravascular
      capillary-type vascular lesions with overlapping morphological details.
      Immunostaining for collagen IV highlighted discriminating features in these
      lesions. Thin basement membranes and glomeruloid architecture are typical of
      glomeruloid hemangiomas, whereas papillae with thick mantles of a basement
      membrane- like matrix enveloping pericytes are prominent in papillary
      hemangiomas. Thus, collagen IV staining patterns provide further evidence that
      papillary and glomeruloid hemangiomas represent distinct histopathological
      entities. This additional technique should allow pathologists to readily
      distinguish between the lesions and make a proper diagnosis. What is important is
      that glomeruloid hemangiomas-often presenting in a spectrum of multiple cutaneous
      vascular lesions, including cherry hemangiomas-are a hallmark of POEMS (acronym
      for polyneuropathy, oganomegaly, endocrinopathy, monoclonal gammopathy, and skin
      changes) syndrome and/or multicentric Castleman's disease, whereas papillary
      hemangiomas clinically present as innocent solitary cutaneous hemangiomas in
      otherwise healthy individuals.

PMID- 18805869
TI  - Extensive ganglioneuromatosis of gallbladder.
AB  - A case of extensive ganglioneuromatosis (GN) of gallbladder is presented. A 38
      year-old man presented with a hepatic hilar mass (O ~ 48 mm) and gall stones. He
      had undergone total thyroidectomy for medullary thyroid carcinoma 8 years
      earlier. The hepatic hilus tumor, which had been clinically suspected to be a
      lymph node metastasis from the medullary thyroid carcinoma, was found to be
      pheochromocytoma. The gallbladder, resected with a clinical diagnosis of
      cholelithiasis, showed extensive transmural GN despite a grossly normal
      appearance. Taking into account the past history, the patient was diagnosed as
      having multiple endocrine neoplasia 2b (MEN2b)-associated GN of gallbladder and
      ectopic pheochromocytoma. As GN of gallbladder in MEN2b has been rarely reported,
      the histological findings are described in detail and a brief review of
      literature is carried out.

PMID- 18805870
TI  - Primary intratesticular spindle cell tumors: interdigitating dendritic cell tumor
      and inflammatory myofibroblastic tumor.
AB  - Spindle cell neoplasms arising in the testis are uncommon; most cases belong to
      the category of gonadal stromal tumors, and the presence of distinctive clinical
      and pathological features usually lead to a definitive diagnosis. In some
      instances, however, the diagnosis of these tumors can be challenging and special
      techniques are needed. The present study reports 2 unusual cases of primary
      intratesticular tumors showing a striking morphology, characterized by spindle to
      stellate cells in a lymphoid background. The diagnosis of interdigitating
      dendritic cell tumor and inflammatory myofibroblastic tumor was established in
      the 2 cases, and their probable origin in cells of the accessory immune system is
      discussed. Although both tumors share similar histological features, their
      immunohistochemical profiles were decisive for a definitive diagnosis.

PMID- 18805871
TI  - Images in pathology. Single thyroid follicle involved by papillary carcinoma:
      partially classic and partially oncocytic.

PMID- 18805872
TI  - Peripheral eosinophilia camouflaging anaplastic large cell lymphoma.
AB  - Eosinophilia is a nonspecific laboratory finding, often noted incidentally during
      routine blood analysis. When persistent, eosinophilia can herald an underlying
      parasitic infection, drug reaction or less commonly, a neoplastic process.
      Anaplastic large cell lymphoma (ALCL) and tissue eosinophilia has been described;
      however, such cases have not displayed marked leukocytosis with eosinophilia.
      This article reports a patient presenting with marked leukocytosis with profound
      peripheral eosinophilia initially thought to be related to a chronic
      myeloproliferative disorder, likely chronic eosinophilic leukemia. After further
      diagnostic evaluation, ALCL was noted in the bone marrow, masked by the myeloid
      hyperplasia and eosinophilia. This case emphasizes the importance of a full
      diagnostic workup for T-cell malignancies, including ALCL rather than focusing on
      the far less common eosinophilia-associated myeloid malignancies in the
      clinicopathologic setting of marked eosinophilia. Moreover, bone marrow
      involvement by ALCL is exceedingly rare and when noted, presents as one or more
      localized lytic lesions. This is the first reported case of ALCL primarily
      involving bone marrow without radiographic evidence of lytic bone lesions.

PMID- 18805873
TI  - Langerhans cell sarcoma involving gallbladder and peritoneal lymph nodes: a case
      report.
AB  - Langerhans cell sarcoma (LCS) is a rare proliferation of Langerhans cells with
      overtly malignant cytologic features and spreads aggressively. LCSs show a
      multiorgan involvement, including skin, lymph nodes, lung, and bone. The authors
      report an LCS in a 74-year-old woman that involved the gallbladder and the
      peritoneal lymph nodes. Imaging revealed a tumor in the gallbladder and the
      peritoneal lymph nodes. The tumor cells were positive for CD1a, S-100 protein,
      and Langerin (CD207). Although the ultrastructural analysis failed to demonstrate
      any Birbeck granules, the histomorphological and immunohistochemical findings
      supported the diagnosis of LCS. After surgical resection, she showed no recurrent
      or metastatic signs for 8 months without any other adjuvant therapy. This is the
      first case of LCS involving the gallbladder and the peritoneal lymph nodes. This
      report also includes a review of the literature concerning this rare disease.

PMID- 18805874
TI  - How do pain and function vary with compartmental distribution and severity of
      radiographic knee osteoarthritis?
AB  - OBJECTIVES: In radiographic OA (ROA) of the knee, how does radiographic severity
      and pattern of compartmental involvement influence symptoms? METHODS: Population
      based study of 819 adults aged > or =50 yrs with knee pain. The severity of knee
      pain and function were measured using the Western Ontario and McMaster
      Universities scale. Three radiographic views of the knees were obtained. RESULTS:
      Seven hundred and seventy-seven participants were eligible (mean age 65.5 yrs,
      357 males). Higher ROA severity in each of the tibiofemoral (TF) and
      patellofemoral (PF) compartments was independently associated with higher mean
      pain scores (TF: F(2, 700) = 9.0, P < 0.0001, PF: F(2, 700) = 12.7, P < 0.0001).
      The same pattern was found for mean function scores (TF: F(2, 705) = 7.1, P =
      0.001, PF: F(2, 705) = 15.9, P < 0.0001). If either the TF or PF compartment was
      affected by moderate/severe OA, the added presence of OA in the other compartment
      did not increase the mean pain or function scores. CONCLUSIONS: It is the
      severity of radiographic disease within a compartment, rather than the
      distribution of radiographic disease between compartments that is associated with
      symptoms. ROA in the PF joint is associated with symptoms, emphasizing the
      importance of radiographic changes in his joint.

PMID- 18805876
TI  - Use of hair colouring products and risk of multiple myeloma among US women.
AB  - OBJECTIVE: To evaluate the association between personal hair dye use and risk of
      multiple myeloma among women. METHODS: A population-based case-control study of
      175 cases of multiple myeloma and 679 controls. Cases and controls were
      interviewed regarding the type and colour of hair colouring product used, age at
      first use, age use stopped, duration, and the frequency of use per year. Odds
      ratios (ORs) and 95% confidence intervals (CI) were estimated using unconditional
      logistic regression to compare never users with four exposure groups: all users,
      ever semi-permanent dye users, ever permanent dye users and dark permanent dye
      users (most frequent use). RESULTS: No association was found between ever
      reporting hair colouring product use and myeloma risk among all users (OR 0.8;
      95% CI 0.5 to 1.1), semi-permanent dye users (OR 0.7; 95% CI 0.4 to 1.2),
      permanent dye users (OR 0.8; 95% CI 0.5 to 1.1) or dark permanent dye users (OR
      0.8; 95% CI 0.5 to 1.3). There were no significant associations among women who
      used hair dyes before 30 years of age, started use before 1980, had >or=240
      lifetime applications, or had used dark permanent dye for 28 or more years.
      CONCLUSION: No evidence of an association between hair colouring product use and
      myeloma risk was found. However, given the conflicting body of literature on hair
      colouring product use and risk of multiple myeloma, this question should be
      further evaluated in larger studies or consortia, and in high risk groups.

PMID- 18805877
TI  - A cross-sectional study of lung function and respiratory symptoms among chemical
      workers producing diacetyl for food flavourings.
AB  - OBJECTIVES: Four diacetyl workers were found to have bronchiolitis obliterans
      syndrome. Exposures, respiratory symptoms, lung function and exposure-response
      relationships were investigated. METHODS: 175 workers from a plant producing
      diacetyl between 1960 and 2003 were investigated. Exposure data were used to
      model diacetyl exposure. Lung function and questionnaire data on respiratory
      symptoms were compared to a general population sample and respiratory symptoms to
      an internal reference group. RESULTS: Workers were potentially exposed to
      acetoin, diacetyl, acetaldehyde and acetic acid. Historic diacetyl exposure
      ranged from 1.8 to 351 mg/m(3), and from 3 to 396 mg/m(3) for specific tasks.
      Diacetyl workers reported significantly more respiratory symptoms compared to the
      general population sample (continuous trouble with breathing (prevalence ratio
      (PR) = 2.6; 95% CI 1.3 to 5.1), daily cough (PR = 1.5; 95% CI 1.1 to 2.1), asthma
      attack (ever) (PR = 2.0; 95% CI 1.2 to 3.4), doctor diagnosed asthma (PR = 2.2;
      95% CI 1.3 to 3.8) and asthma attack in the last year (PR = 4.7; 95% CI 1.9 to
      11.4)) and to a minimally exposed internal reference group (ever trouble with
      breathing (PR = 2.8; 95% CI 1.1 to 7.0) and work-related shortness of breath in
      the last year (PR = 7.5; 95% CI 1.1 to 52.9)). Lung function did not differ
      between groups. A positive relationship between exposure and FEV(1) was found.
      CONCLUSION: The excess of respiratory symptoms in this retrospective cohort
      suggests that diacetyl production poses an occupational hazard. Limited
      historical exposure data did not support a quantitative individual diacetyl
      exposure-response relationship, but our findings suggest that preventive measures
      are prudent.

PMID- 18805878
TI  - Future needs of occupational epidemiology of extremely low frequency electric and
      magnetic fields: review and recommendations.
AB  - The occupational epidemiological literature on extremely low frequency electric
      and magnetic fields (EMF) and health encompasses a large number of studies of
      varying design and quality that have addressed many health outcomes, including
      various cancers, cardiovascular disease, depression and suicide, and
      neurodegenerative diseases, such as Alzheimer disease and amyotrophic lateral
      sclerosis (ALS). At a 2006 workshop we reviewed studies of occupational EMF
      exposure with an emphasis on methodological weaknesses, and proposed analytical
      ways to address some of these. We also developed research priorities that we hope
      will address remaining uncertainties. Broadly speaking, extensive epidemiological
      research conducted during the past 20 years on occupational EMF exposure does not
      indicate strong or consistent associations with cancer or any other health
      outcomes. Inconsistent results for many of the outcomes may be attributable to
      numerous shortcomings in the studies, most notably in exposure assessment. There
      is, however, no obvious correlation between exposure assessment quality and
      observed associations. Nevertheless, for future research, the highest priorities
      emerge in both the areas of exposure assessment and investigation of ALS. To
      better assess exposure, we call for the development of a more complete job
      exposure matrix that combines job title, work environment and task, and an index
      of exposure to electric fields, magnetic fields, spark discharge, contact
      current, and other chemical and physical agents. For ALS, we propose an
      international collaborative study capable of illuminating a reported association
      with electrical occupations by disentangling the potential roles of electric
      shocks, magnetic fields and bias. Such a study will potentially lead to evidence
      based measures to protect public health.

PMID- 18805879
TI  - Does return to work occur earlier after work-related sick leave episodes than
      after non-work-related sick leave episodes? A retrospective cohort study in
      Spain.
AB  - OBJECTIVE: In Spain, sick pay benefits for work-related sick leave episodes are
      higher than for non-work-related episodes. Our aim is to assess whether time to
      return to work is longer for higher paid sick leave episodes than for lower paid
      episodes. METHODS: We used data from 62,376 work-related and 76,932 non-work
      related sick leave episodes occurring among 338,226 workers from 56,099 companies
      in Spain in 2002. All episodes were followed for up to 18 months. Episodes were
      classified by a physician as being work- or non-work-related according to medico
      legal judgments. The median episode duration and the 25th and 75th percentiles
      were calculated. The probability of remaining absent from work was estimated by a
      non-parametric estimator of the marginal survival function. The time ratio
      between both types of sick leave was estimated by a log-logistic regression
      model, using non-work-related episodes as the reference. RESULTS: Median episode
      duration (25th-75th percentiles) was 11 (6-21) days for work-related episodes and
      9 (4-29) days for non-work-related episodes. Time to return to work was longer
      for work-related episodes than for non-work-related episodes of less than 16 days
      (time ratio: 1.19 in men and 1.08 in women), while the opposite was observed for
      episodes of more than 15 days (0.58 in men and 0.40 in women). CONCLUSIONS: Sick
      pay benefits have a limited effect on time to return to work after a sick leave
      episode.

PMID- 18805880
TI  - Performance of self-reported occupational exposure compared to a job-exposure
      matrix approach in asthma and chronic rhinitis.
AB  - OBJECTIVES: Self-reported exposure to vapours, gas, dust or fumes (VGDF) has been
      widely used as an occupational exposure metric in epidemiological studies of
      chronic lung diseases. Our objective was to characterise the performance of VGDF
      for repeatability, systematic misclassification, and sensitivity and specificity
      against exposure likelihood by a job-exposure matrix (JEM). METHODS: We analysed
      data from two interviews, 24 months apart, of adults with asthma and chronic
      rhinitis. Using distinct job as the unit of analysis, we tested a single response
      item (exposure to VGDF) against assignment using a JEM. We further analysed VGDF
      and the JEM among a subset of 199 subjects who reported the same job at both
      interviews, using logistic regression analysis to test factors associated with
      VGDF inconsistency and discordance with the JEM. RESULTS: VGDF was reported for
      193 (44%) of 436 distinct jobs held by the 348 subjects studied; moderate to high
      exposure likelihood by JEM was assigned to 120 jobs (28%). The sensitivity and
      specificity of VGDF against JEM were 71% and 66%, respectively. Among 199
      subjects with the same job at both interviews, 32% had a discordant VGDF status
      (kappa = 0.35). Those with chronic rhinitis without concomitant asthma compared
      to asthma alone were more likely to have a VGDF report discordant with the JEM
      (OR 3.6, 95% CI 1.4 to 9.0; p = 0.01). Rhinitis was also associated with reported
      VGDF in a job classified by the JEM as low exposure (OR 3.9, 95% CI 1.6 to 9.4; p
      = 0.003). CONCLUSION: The VGDF item is moderately sensitive measured against JEM
      as a benchmark. The measure is a useful assessment method for epidemiological
      studies of occupational exposure risk.

PMID- 18805881
TI  - Lung cancer mortality and iron oxide exposure in a French steel-producing
      factory.
AB  - OBJECTIVE: To study the possible association between iron oxide exposures and
      lung cancer risk among workers in a French carbon steel-producing factory.
      METHODS: 16 742 males and 959 females ever employed for at least 1 year between
      1959 and 1997 were followed up for mortality from January 1968 to December 1998.
      Causes of death were ascertained from death certificates. Job histories and
      smoking habits were available for 99.7% and 72.3% of subjects, respectively.
      Occupational exposures were assessed by a factory-specific job-exposure matrix
      (JEM) validated with atmospheric measurements. Standardised mortality ratios
      (SMRs) were computed using local death rates (external references). Poisson
      regressions were used to estimate the relative risks (RRs) for occupational
      exposures (internal references), adjusted on potential confounding factors.
      RESULTS: Among males, observed mortality was lower than expected for lung cancer
      compared to the local population (233 deaths, SMR 0.89, 95% CI 0.78 to 1.01) and
      higher than expected compared to the French population (SMR 1.30, 95% CI 1.15 to
      1.48) No lung cancer excess was observed for exposure to iron oxides (RR 0.80,
      95% CI 0.55 to 1.17) and no dose-response relationship with intensity, duration
      of exposure or cumulative index was found. A significant bladder cancer excess
      was observed among workers exposed to oil mist (RR 2.44, 95% CI 1.06 to 5.60),
      increasing significantly with intensity, duration of exposure and cumulative
      index. CONCLUSION: This study did not detect any relationship between exposure to
      iron oxides and lung cancer mortality. An excess of mortality from bladder cancer
      was found among workers exposed to oil mist.

PMID- 18805882
TI  - Predicted mortality from malignant mesothelioma among women exposed to blue
      asbestos at Wittenoom, Western Australia.
AB  - INTRODUCTION: Nearly 3000 women and girls were documented to have lived at the
      blue asbestos mining and milling town of Wittenoom in Western Australia between
      1943 and 1992. Eight per cent of deaths among these women to the end of 2004 have
      been from malignant mesothelioma of the pleura. AIM: To predict future mortality
      from mesothelioma to 2030 in this cohort. METHODS: Mesothelioma mortality rates
      incorporating parameters for cumulative exposure, a power of time since first
      exposure and annual rates of fibre clearance from the lung were calculated from
      maximum likelihood estimates. These rates plus age specific mortality rates for
      Western Australian females incorporating an excess lung cancer risk were then
      applied to all Wittenoom cohort women surviving to the end of 2004, in yearly
      increments, to predict the future numbers of cases of mesothelioma to 2030.
      RESULTS: There were 40 deaths from mesothelioma among the Wittenoom women to the
      end of 2004. Using a range of models that incorporate time since first exposure,
      competing risks from other diseases, latency periods and clearance of
      mesothelioma from the lungs we predict 66 (lowest estimate) to 87 (highest
      estimate) deaths from mesothelioma until 2030. This represents one and a half to
      two and a half times the number of deaths that have already occurred to the end
      of 2004. CONCLUSION: The high toll from mesothelioma in this cohort of women and
      girls will continue well into the future.

PMID- 18805883
TI  - Cumulative exposure to high-strain and active jobs as predictors of cognitive
      function: the Whitehall II study.
AB  - OBJECTIVES: A high-strain job (a combination of high job demands and low job
      control) is expected to increase the risk of health problems, whereas an active
      job (high demands and high control) can be hypothesised to be associated with a
      greater capacity to learn. We tested associations between high-strain and active
      jobs and cognitive function in middle-aged men and women. METHODS: Data on 4146
      British civil servants (2989 men and 1157 women) aged 35-55 years at baseline
      came from the Whitehall II study. Cumulative exposure to both high-strain and
      active jobs was assessed at phases 1 (1985-1988), 2 (1989-1990) and 3 (1991
      1993). Cognitive performance was assessed at phases 5 (1997-1999) and 7 (2003
      2004) using the following tests: verbal memory, inductive reasoning (Alice Heim),
      verbal meaning (Mill Hill), phonemic and semantic fluency. Analyses were adjusted
      for age, sex and employment grade. RESULTS: Longer exposure to high job strain
      and shorter exposure to active jobs were associated with lower scores in most of
      the cognitive performance tests. However, these associations disappeared on
      adjustment for employment grade. Phonemic fluency was an exception to this
      pattern. Associations between exposure to an active job and phonemic fluency at
      both follow-up phases were robust to adjustment for employment grade. However,
      there was no association between exposure to active jobs and change in phonemic
      fluency score between the follow-up phases after adjustment for employment grade.
      CONCLUSIONS: In these data, associations between cumulative exposure to high
      strain or active jobs and cognition are largely explained by socioeconomic
      position.

PMID- 18805884
TI  - Mortality and cancer incidence of Australian participants in the British nuclear
      tests in Australia.
AB  - OBJECTIVES: To investigate the mortality and cancer incidence of Australian
      nuclear test participants, and to identify any association with exposure to
      ionising radiation. METHODS: A retrospective cohort study was carried out in
      which the mortality and cancer incidence rates of participants (n = 10,983) were
      compared with rates in the general male Australian population. Dose
      reconstructions were carried out by a panel of health physicists. Mortality and
      cancer rates were compared with the general population and between groups of
      subjects categorised by assessed radiation exposure. RESULTS: All-cause mortality
      was not raised. Mortality and incidence were significantly raised for cancers of
      the head and neck, lung, colon and rectum, and prostate, and for all cancers
      combined. For oesophageal cancer, melanoma, all leukaemias and non-chronic
      lymphatic leukaemia (non-CLL leukaemia), incidence was significantly raised, but
      mortality was non-significantly raised. No association was found between
      radiation exposure and overall cancer incidence or mortality, or with any cancer
      or cancer deaths occurring in excess. CONCLUSIONS: There is no evidence that the
      excess cancers and cancer deaths were caused by radiation exposure at the test
      sites. Possible contributing factors are high smoking prevalence and demographic
      differences from the Australian population with whom rates were compared.
      Asbestos is a likely contributor to some cancers in naval personnel.

PMID- 18805885
TI  - Socio-economic differences in the association between sickness absence and
      mortality: the prospective DREAM study of Danish private sector employees.
AB  - OBJECTIVES: To examine duration of sickness absence as a risk marker for future
      mortality by socio-economic position among all private sector employees in
      Denmark in 1998-2004. METHODS: All residents in Denmark employed in the private
      sector receiving sickness absence compensation in 1998 were investigated in a
      prospective cohort study. 236 207 persons (38.2% women, 61.8% men, age range 18
      65, mean age 37.8 years) alive on 1 January 2001 were included in the study.
      Mortality from 1 January 2001 to 31 December 2004 was assessed using national
      register data. Deaths in 1999 and 2000 were excluded to determine the status of
      sickness absence duration as an early risk marker. For analyses within
      occupational grades, data were available for a sub-population of 137 607 study
      participants. RESULTS: 3040 persons died during follow-up. The age-adjusted risk
      of future mortality increased by duration of sickness absence in a graded fashion
      among men and non-blue collar workers. Among women and blue collar workers, there
      was no association of mortality with duration of sickness absences below 6 weeks.
      However, employees with > or =6 weeks of absence compared to those with 1-week
      absence had a substantial excess risk of death in all groups: adjusted hazard
      ratio 2.2 (95% CI 1.8 to 2.7) for women, 2.1 (95% CI 1.8 to 2.4) for men, 3.7
      (95% CI 1.9 to 7.2) in white collar occupations, 3.3 (95% CI 2.2 to 5.0) in
      intermediate grade occupations and 2.0 (95% CI 1.7 to 2.3) in blue collar
      occupations. CONCLUSION: Administratively collected data on sickness absence
      compensation for periods > or =6 weeks identified "at risk" groups for future
      excess mortality in male and female private sector employees across occupational
      grade levels.

PMID- 18805886
TI  - Occupation/industry and risk of non-Hodgkin's lymphoma in the United States.
AB  - AIMS: To identify occupations and industries associated with non-Hodgkin's
      lymphoma (NHL) in a large population-based, case-control study in the USA.
      METHODS: Cases (n = 1189) of histologically confirmed malignant NHL ages 20-74
      were prospectively identified in four geographic areas covered by the National
      Cancer Institute SEER Program. Controls (n = 982) were selected from the general
      population by random digit dialling (<65 years of age) and from residents listed
      in Medicare files (65-74 years of age). Odds ratios and 95% confidence intervals
      for occupations and industries were calculated by unconditional logistic
      regression analyses, adjusting for age, gender, ethnicity and study centre.
      Further analyses stratified for gender and histological subtype were also
      performed. RESULTS: Risk of NHL was increased for a few occupations and
      industries. Several white collar occupations, with no obvious hazardous
      exposures, had elevated risks, including purchasing agents and buyers, religious
      workers, physical therapists and information clerks. Occupations with excesses
      that may have exposures of interest include launderers and ironers, service
      occupations, food/beverage preparation supervisors, hand packers and packagers,
      roofing and siding, leather and leather products, transportation by air, nursing
      and personal care facilities, and specialty outpatient clinics. Significantly
      decreased risks of NHL were found for a number of occupations and industries
      including post-secondary teachers and chemical and allied products. CONCLUSIONS:
      The results of this study suggest that several occupations and industries may
      alter the risk of NHL. Our results support previously reported increased risks
      among farmers, printers, medical professionals, electronic workers and leather
      workers. These findings should be evaluated further in larger studies that have
      the power to focus on specific exposures and histological subtypes of NHL.

PMID- 18805887
TI  - Work pattern causes bias in self-reported activity duration: a randomised study
      of mechanisms and implications for exposure assessment and epidemiology.
AB  - BACKGROUND: Self-reported activity duration is used to estimate cumulative
      exposures in epidemiological research. OBJECTIVE: The effects of work pattern,
      self-reported task dullness (a measure of cognitive task demand), and heart rate
      ratio and perceived physical exertion (measures of physical task demands) on
      error in task duration estimation were investigated. METHODS: 24 participants (23
      54 years old, 12 males) were randomly assigned to execute three tasks in either a
      continuous (three periods of 40 continuous minutes, one for each task) or a
      discontinuous work pattern (40 min tasks each divided into four periods of 4, 8,
      12 and 16 min). Heart rate was measured during tasks. After completing the 2 h
      work session, subjects reported the perceived duration, dullness and physical
      exertion for each of the three tasks. Multivariate models were fitted to analyse
      errors and their absolute value to assess the accuracy in task duration
      estimation and the mediating role of task demands on the observed results.
      RESULTS: Participants overestimated the time spent shelving boxes (up to 38%) and
      filing journals (up to 9%), and underestimated the time typing articles (up to 
      22%). Over- and underestimates and absolute errors were greater in the
      discontinuous work pattern group. Only the self-reported task dullness mediated
      the differences in task duration estimation accuracy between work patterns.
      CONCLUSIONS: Task-related factors can affect self-reported activity duration.
      Exposure assessment strategies requiring workers to allocate work time to
      different tasks could result in biased measures of association depending on the
      demands of the tasks during which the exposure of interest occurs.

PMID- 18805888
TI  - Estimates of historical exposures by phase contrast and transmission electron
      microscopy in North Carolina USA asbestos textile plants.
AB  - OBJECTIVES: To develop a job-exposure matrix (JEM) for fibre exposures in three
      asbestos textile plants and to develop estimates of fibre size-specific
      exposures. METHODS: Historical dust samples from three North Carolina, USA
      asbestos textile plants were obtained. Plant specific samples were used to
      express impinger dust concentrations as fibre concentrations by phase contract
      microscopy (PCM). Mixed models were used to estimate PCM exposures by plant,
      department, job and calendar time. Archived membrane filter samples were analysed
      by transmission electron microscopy (TEM) to determine the bivariate
      diameter/length distribution of airborne fibres by plant and operation. RESULTS:
      PCM fibre levels estimated from the models were very high in the 1930s, with some
      operations having in excess of 200 fibres/ml, and decreased appreciably over
      time. TEM results for 77 airborne dust samples found that only a small proportion
      of airborne fibres were measured by PCM (>0.25 microm in diameter and >5 microm
      in length) and the proportion varied considerably by plant and operation (range
      2.9% to 10.0%). The bivariate diameter/length distribution of airborne fibres
      demonstrated a relatively high degree of variability by plant and operation. PCM
      adjustment factors also varied substantially across plants and operations.
      CONCLUSIONS: These data provide new information concerning airborne fibre levels
      and characteristics in three historically important asbestos textile plants. PCM
      concentrations were high in the early years and TEM data demonstrate that the
      vast majority of airborne fibres inhaled by the workers were shorter than 5
      microm in length, and thus not included in the PCM-based fibre counts.

PMID- 18805889
TI  - Dust and chemical exposures, and miscarriage risk among women textile workers in
      Shanghai, China.
AB  - INTRODUCTION: To investigate possible associations between miscarriage and
      occupational exposures in the Shanghai textile industry. METHODS: A retrospective
      cohort study of miscarriages among 1752 women in the Shanghai textile industry
      was conducted. Reproductive history was self-reported by women and occupational
      work histories were collected from factory personnel records. Occupational
      exposures were assigned by linking work history information to an industry
      specific job-exposure matrix informed by factory-specific textile process
      information and industrial hygiene assessments. Estimates of cotton dust and
      endotoxin exposure were also assigned. Odds ratios (OR) and 95% CI were estimated
      by multivariate logistic regression, with adjustment for age at pregnancy,
      educational level, smoking status of the woman and her spouse, use of alcohol,
      and woman's year of birth. RESULTS: An elevation in risk of a spontaneously
      aborted first pregnancy was associated with exposure to synthetic fibres (OR
      1.89, 95% CI 1.20 to 3.00) and mixed synthetic and natural fibres (OR 3.31, 95%
      CI 1.30 to 8.42). No increased risks were observed for women working with
      solvents, nor were significant associations observed with quantitative cotton
      dust or endotoxin exposures. Associations were robust and similar when all
      pregnancies in a woman's reproductive history were considered. CONCLUSIONS:
      Occupational exposure to synthetic fibres may cause miscarriages, and this
      possibility should be the subject of further investigation.

PMID- 18805891
TI  - Endovascular repair after stent elephant trunk procedure for extensive thoracic
      aortic aneurysm.
AB  - Hybrid surgical-endovascular procedure was conducted in a 46-year-old male with
      extensive thoracic aortic aneurysm. Ascending aorta and arch replacement combined
      with stent elephant trunk implantation was performed first. An open stent-graft
      was implanted into the descending aorta. One month later, endovascular repair was
      conducted. Postoperative CTA showed total coverage of the descending aorta by
      stent-grafts and the descending aortic aneurysm was totally thrombo-excluded.
      Stent elephant trunk may be a better alternative to conventional elephant trunk
      in hybrid surgical-endovascular approaches in treatment of extensive thoracic
      aortic aneurysm.

PMID- 18805892
TI  - TNFbeta+250 polymorphism and hyperdynamic state in cardiac surgery with
      extracorporeal circulation.
AB  - We have investigated genetic and clinical factors associated with hyperdynamic
      state (HS) after heart surgery with extracorporeal circulation (ECC). We
      performed a prospective cohort study of consecutive patients who underwent
      elective heart surgery with ECC. HS was defined as hyperthermia (>38 degrees C),
      cardiac index (CI) >3.5 l/min/m(2) and systemic vascular resistance index (SVRI)
      <1600 dynes x s/cm(5) x m(2). The study included demographic variables, gene
      polymorphisms A/G of tumor necrosis factor-beta (TNFbeta+250), G/A-1082 of
      interleukin-10 (IL-10), polymorphism of interleukin-1 receptor antagonist (IL
      1ra), comorbidity, type of surgery, serum levels of interleukin-6 (IL-6), and
      postoperative course. We used Pearson chi(2) or Fisher exact test, and Student t
      test for univariate analysis, with forward stepwise logistic regression for
      multivariate adjustment. Eighty patients were studied, of whom 22 (27.5%)
      developed HS. The presence of allele G of TNFbeta+250 polymorphism was associated
      with an increased incidence of HS (68% vs. 37%; P=0.011). In the multivariate
      analysis, a longer duration of ECC, and the presence of the G allele, were
      associated with the development of HS. The G allele of TNFbeta+250 polymorphism,
      and prolonged extracorporeal circuit times, may favor the development of a
      hyperdynamic state after heart surgery with ECC.

PMID- 18805893
TI  - Does surgical correction of coarctation of the aorta in adults reduce established
      hypertension?
AB  - A best evidence topic in cardiac surgery was written according to a structured
      protocol. The question addressed was whether surgical correction of coarctation
      of the aorta in adults (>16 years) results in reduction in established
      hypertension. Altogether 484 relevant papers were identified using the below
      mentioned search, 11 papers represented the best evidence to answer the question.
      The author, journal, date and country of publication, patient group studied,
      study type, relevant outcomes, results and study weaknesses were tabulated. We
      conclude that surgical repair of coarctation of the aorta in adult patients is
      superior to conservative management in the reduction of established hypertension,
      with one meta-analysis and several retrospective reviews reporting low morbidity
      and low risk of re-stenosis. The reduction in blood pressure postoperatively has
      been demonstrated consistently, with most patients reported as normotensive
      without medication and the remainder having reduced requirements for
      antihypertensive medications. In all the papers included here (except one), there
      was no early mortality and no procedure-related late mortality during mean follow
      up ranging from 2 to 14 years. Thus, surgical correction of aortic coarctation is
      a relatively safe procedure.

PMID- 18805894
TI  - Successful angiographic embolisation of bleeding into the chest wall after chest
      drain insertion.
AB  - Peripheral arterial injuries after blunt or penetrating trauma commonly follow
      injuries to adjacent soft tissue and bone. The traditional approach to these
      injuries is by open exploration, with identification and ligation of the bleeding
      vessel. We describe the case of a type II respiratory failure patient who had an
      enormous pectoral muscle haematoma following chest drain insertion, in whom the
      bleeding was only controlled by angiographic embolisation following failure of
      surgical exploration.

PMID- 18805895
TI  - Role of CYP epoxygenases in A2A AR-mediated relaxation using A2A AR-null and wild
      type mice.
AB  - We hypothesized that A2A adenosine receptor (A2A AR) activation causes
      vasorelaxation through cytochrome P-450 (CYP) epoxygenases and endothelium
      derived hyperpolarizing factors, whereas lack of A2A AR activation promotes
      vasoconstriction through Cyp4a in the mouse aorta. Adenosine 5'-N
      ethylcarboxamide (NECA; 10(-6) M), an adenosine analog, caused relaxation in wild
      type A2A AR (A2A AR+/+; +33.99 +/- 4.70%, P < 0.05) versus contraction in A2A AR
      knockout (A2A AR(-/-); -27.52 +/- 4.11%) mouse aortae. An A2A AR-specific
      antagonist (SCH-58261; 1 microM) changed the NECA (10(-6) M) relaxation response
      to contraction (-35.82 +/- 4.69%, P < 0.05) in A2A AR+/+ aortae, whereas no
      effect was noted in A2A AR(-/-) aortae. Significant contraction was seen in the
      absence of the endothelium in A2A AR+/+ (-2.58 +/- 2.25%) aortae compared with
      endothelium-intact aortae. An endothelial nitric oxide synthase inhibitor (N
      nitro-L-arginine methyl ester; 100 microM) and a cyclooxygenase inhibitor
      (indomethacin; 10 microM) failed to block NECA-induced relaxation in A2A AR+/+
      aortae. A selective inhibitor of CYP epoxygenases (methylsulfonyl
      propargyloxyphenylhexanamide; 10 microM) changed NECA-mediated relaxation (-22.74
      +/- 5.11% at 10(-6) M) and CGS-21680-mediated relaxation (-18.54 +/- 6.06% at 10(
      6) M) to contraction in A2A AR+/+ aortae, whereas no response was noted in A2A
      AR(-/-) aortae. Furthermore, an epoxyeicosatrienoic acid (EET) antagonist [14,15
      epoxyeicosa-5(Z)-enoic acid; 10 microM] was able to block NECA-induced relaxation
      in A2A AR+/+ aortae, whereas omega-hydroxylase inhibitors (10 microM dibromo
      dodecenyl-methylsulfimide and 10 microM HET-0016) changed contraction into
      relaxation in A2A AR(-/-) aorta. Cyp2c29 protein was upregulated in A2A AR+/+
      aortae, whereas Cyp4a was upregulated in A2A AR(-/-) aortae. Higher levels of
      dihydroxyeicosatrienoic acids (DHETs; 14,15-DHET, 11,12-DHET, and 8,9-DHET, P <
      0.05) were found in A2A AR+/+ versus A2A AR(-/-) aortae. EET levels were not
      significantly different between A2A AR+/+ and A2A AR(-/-) aortae. It is concluded
      that CYP epoxygenases play an important role in A2A AR-mediated relaxation, and
      the deletion of the A2A AR leads to contraction through Cyp4a.

PMID- 18805896
TI  - Role of estrogen receptor subtypes in estrogen-induced organ-specific
      vasorelaxation after trauma-hemorrhage.
AB  - Although endothelin-1 (ET-1)-induced organ hypoperfusion after trauma-hemorrhage
      is improved by estrogen administration, it remains unclear whether estrogen
      receptor (ER) subtypes play any role in the attenuation of ET-1-induced
      vasoconstriction in any specific organ bed. To investigate this, isolated
      perfusion experiments in the heart, liver, small intestine, kidney, and lung were
      carried out in sham, at the time of maximum bleedout (MBO; i.e., 5-cm midline
      incision, with removal of 60% of circulating blood volume over 45 min to maintain
      a mean blood pressure of 40 mmHg), and 2 h after trauma-hemorrhage and
      resuscitation (T-H/R). Organ-specific ET-1-induced vasoconstriction was
      evaluated, and the effects of 17beta-estradiol (E2) and ER-specific agonists
      propylpyrazole triol (PPT; ERalpha agonist) and diarylpropionitrile (DPN; ERbeta
      agonist) were determined. ET-1 induced the greatest vasoconstriction in sham
      animals, with the strongest response in the kidneys, followed by the small
      intestine and liver. ET-1-induced responses were weakest in the heart and lungs.
      ET-1-induced vasoconstriction was evident at the time of MBO but was
      significantly decreased at 2 h after T-H/R. ERbeta plays an important role in
      cardiac performance, as evidenced by improved heart performance (+dP/dt) in the
      presence of DPN. DPN also induced a greater effect than PPT in the reduction of
      ET-1-induced vasoconstriction in the kidneys and lungs. In contrast, PPT
      attenuated ET-1-induced vasoconstriction in the liver, whereas both DPN and PPT
      were equally effective in the small intestine. The increased +dP/dt values
      induced by E2, DPN, or PPT were evident at the time of MBO but were significantly
      decreased at 2 h after T-H/R. These data indicate that the effects of ET-1 on
      vasoconstriction and the role of ER subtypes in estrogen-induced vasorelaxation
      are organ specific and temporally specific after trauma-hemorrhage.

PMID- 18805898
TI  - Fluid shear stress modulates endothelial cell invasion into three-dimensional
      collagen matrices.
AB  - Endothelial cells are subjected to biochemical and mechanical stimuli, which
      regulate their angiogenic potential. We determined the synergistic effects of
      sphingosine-1-phosphate (S1P) and fluid wall shear stress (WSS) on a previously
      established model of human umbilical vein endothelial cell invasion into three
      dimensional collagen matrices. Collagen matrices were incorporated into a
      parallel-plate flow chamber to apply controlled WSS to the surface of endothelial
      monolayers over a period of 24 h. Cell invasion required the presence of S1P,
      with the effects of S1P being enhanced by shear stress to an extent comparable
      with S1P combined with angiogenic growth factor stimulation. The number of
      invading cells depended on the magnitude of shear stress, with a maximal
      induction at a shear stress of approximately 5 dyn/cm2, whereas the invasion
      distance was proportional to the magnitude of shear stress. The enhancement of
      invasion by 5.3 dyn/cm2 shear stress coincided with elevated phosphorylation of
      Akt and matrix metalloproteinase (MMP)-2 activation. Furthermore, invasion
      induced by the combined application of WSS and S1P was attenuated by inhibitors
      of MMPs (GM6001) and the phosphatidylinositol 3-kinase/Akt signaling pathway
      (wortmannin). These results provide evidence that shear stress is a positive
      modulator of S1P-induced endothelial cell invasion into collagen matrices through
      enhanced Akt and MMP-2 activation.

PMID- 18805897
TI  - Human neutrophil peptides: a novel potential mediator of inflammatory
      cardiovascular diseases.
AB  - The traditional view of atherosclerosis has recently been expanded from a
      predominantly lipid retentive disease to a coupling of inflammatory mechanisms
      and dyslipidemia. Studies have suggested a novel role for polymorphonuclear
      neutrophil (PMN)-dominant inflammation in the development of atherosclerosis.
      Human neutrophil peptides (HNPs), also known as alpha-defensins, are secreted and
      released from PMN granules upon activation and are conventionally involved in
      microbial killing. Current evidence suggests an important immunomodulative role
      for these peptides. HNP levels are markedly increased in inflammatory diseases
      including sepsis and acute coronary syndromes. They have been found within the
      intima of human atherosclerotic arteries, and their deposition in the skin
      correlates with the severity of coronary artery diseases. HNPs form complexes
      with LDL in solution and increase LDL binding to the endothelial surface. HNPs
      have also been shown to contribute to endothelial dysfunction, lipid metabolism
      disorder, and the inhibition of fibrinolysis. Given the emerging relationship
      between PMN-dominant inflammation and atherosclerosis, HNPs may serve as a link
      between them and as a biological marker and potential therapeutic target in
      cardiovascular diseases including coronary artery diseases and acute coronary
      syndromes.

PMID- 18805899
TI  - Ser9 phosphorylation of mitochondrial GSK-3beta is a primary mechanism of
      cardiomyocyte protection by erythropoietin against oxidant-induced apoptosis.
AB  - The aim of this study was to determine the role of GSK-3beta in cardiomyocyte
      protection afforded by erythropoietin (EPO) against oxidant stress-induced
      apoptosis. Treatment with EPO (10 units/ml) induced Ser473 phosphorylation of Akt
      and Ser9 phosphorylation of GSK-3beta and significantly reduced the proportion of
      apoptotic H9c2 cardiomyocytes after exposure to H2O2 from 38.3 +/- 2.7% to 26.0
      +/- 2.9%. This protection was not detected in cells transfected with
      constitutively active GSK-3beta (S9A), which lacks Ser9 for inhibitory
      phosphorylation. The antiapoptotic effect of EPO was mimicked completely by GSK
      3beta knockdown using small interfering RNA and partly by the transfection with
      kinase-deficient GSK-3beta (K85R). The level of colocalization of intracellular
      GSK-3beta with mitochondria assessed by enhanced green fluorescent protein-tagged
      GSK-3beta or immunocytochemistry was not altered by EPO treatment. However, EPO
      increased the level of Ser9-phospho-GSK-3beta colocalized with mitochondria by
      50% in a phosphatidylinositol 3-kinase-dependent manner. Mitochondrial
      translocation of Bcl-2-associated X protein (BAX) after exposure to H2O2 was
      inhibited by EPO pretreatment and by GSK-3beta knockdown. These results suggest
      that the suppression of GSK-3beta activity by Akt-mediated Ser9 phosphorylation
      in the mitochondria affords cardiomyocytes tolerance against oxidant-induced
      apoptosis, possibly by inhibiting the access of BAX to the mitochondria.

PMID- 18805900
TI  - The association of coronary artery calcification and carotid artery intima-media
      thickness with distinct, traditional coronary artery disease risk factors in
      asymptomatic adults.
AB  - Coronary artery calcification (CAC) and common carotid artery intima-media
      thickness (CIMT) are measures of subclinical vascular disease. This 2000-2006
      study aimed to characterize the associations among coronary artery disease risk
      factors, CAC quantity, and CIMT and to estimate shared genetic and environmental
      contributions to both CAC and CIMT among 478 asymptomatic Amish adults in
      Lancaster County, Pennsylvania. Heritability for CAC quantity and CIMT, adjusted
      for age and sex, was 0.42 (P = 0.0001) and 0.29 (P = 0.003), respectively. CAC
      quantity and CIMT were modestly correlated (adjusted r = 0.14, P = 0.003) but
      showed little evidence of shared genetic or environmental factors. However,
      significant genetic correlations were found for CAC quantity and total
      cholesterol (0.44 (standard error, 0.19); P = 0.03), for CAC quantity and low
      density lipoprotein cholesterol (0.55 (standard error, 0.17); P = 0.005), and for
      CIMT and waist circumference (0.58 (standard error, 0.25); P = 0.046), suggesting
      shared genes for these risk factors and measures of subclinical disease. Results
      suggest that some of the same genes influence variation in CAC and low density
      lipoprotein cholesterol, whereas a different set of genes influences variation in
      CIMT and waist circumference.

PMID- 18805901
TI  - Web-based applications for building, managing and analysing kinetic models of
      biological systems.
AB  - Mathematical modelling and computational analysis play an essential role in
      improving our capability to elucidate the functions and characteristics of
      complex biological systems such as metabolic, regulatory and cell signalling
      pathways. The modelling and concomitant simulation render it possible to predict
      the cellular behaviour of systems under various genetically and/or
      environmentally perturbed conditions. This motivates systems
      biologists/bioengineers/bioinformaticians to develop new tools and applications,
      allowing non-experts to easily conduct such modelling and analysis. However,
      among a multitude of systems biology tools developed to date, only a handful of
      projects have adopted a web-based approach to kinetic modelling. In this report,
      we evaluate the capabilities and characteristics of current web-based tools in
      systems biology and identify desirable features, limitations and bottlenecks for
      further improvements in terms of usability and functionality. A short discussion
      on software architecture issues involved in web-based applications and the
      approaches taken by existing tools is included for those interested in developing
      their own simulation applications.

PMID- 18805902
TI  - Technological developments in lipidomics.
AB  - Lipid analysis is a well-established field of research that focuses on one lipid
      or a few lipids. The recent developments in mass spectrometry technologies have
      enabled more comprehensive studies to be performed on lipids present in a sample.
      The move towards extensive lipid research has led to the coining of the term
      lipidomics, which is defined as the ensemble of lipids present in a sample. In
      this review, we will discuss the technical developments in the field of
      lipidomics and the current limitations of this nascent field.

PMID- 18805903
TI  - Postural orthostatic tachycardia syndrome is an under-recognized condition in
      chronic fatigue syndrome.
AB  - BACKGROUND: It has been suggested that postural orthostatic tachycardia syndrome
      (POTS) be considered in the differential diagnosis of those with chronic fatigue
      syndrome/myalgic encephalomyelitis (CFS/ME). Currently, measurement of
      haemodynamic response to standing is not recommended in the UK NICE CFS/ME
      guidelines. OBJECTIVES: To determine prevalence of POTS in patients with CFS/ME.
      DESIGN: Observational cohort study. METHODS: Fifty-nine patients with CFS/ME
      (Fukuda criteria) and 52 age- and sex-matched controls underwent formal autonomic
      assessment in the cardiovascular laboratory with continuous heart rate and beat
      to-beat blood pressure measurement (Task Force, CNSystems, Graz Austria).
      Haemodynamic responses to standing over 2 min were measured. POTS was defined as
      symptoms of orthostatic intolerance associated with an increase in heart rate
      from the supine to upright position of >30 beats per minute or to a heart rate of
      >120 beats per minute on standing. RESULTS: Maximum heart rate on standing was
      significantly higher in the CFS/ME group compared with controls (106 +/- 20 vs.
      98 +/- 13; P = 0.02). Of the CFS/ME group, 27% (16/59) had POTS compared with 9%
      (5) in the control population (P = 0.006). This difference was predominantly
      related to the increased proportion of those in the CFS/ME group whose heart rate
      increased to >120 beats per minute on standing (P = 0.0002). Increasing fatigue
      was associated with increase in heart rate (P = 0.04; r(2) = 0.1). CONCLUSION:
      POTS is a frequent finding in patients with CFS/ME. We suggest that clinical
      evaluation of patients with CFS/ME should include response to standing. Studies
      are needed to determine the optimum intervention strategy to manage POTS in those
      with CFS/ME.

PMID- 18805904
TI  - Development, impact and outcomes of the Hull Bacteraemia Service.
AB  - BACKGROUND: Bacteraemia is a significant cause of mortality and healthcare
      expenditure. Evidence suggests that consultation by an infection specialist may
      improve outcomes. AIM: To review the characteristics and outcomes of patients
      seen by a newly implemented bacteraemia service. METHODS: Retrospective review of
      data collected at time of consultation. Economic analyses and benchmarking of
      outcomes were also performed. RESULTS: One hundred and fifty-one patients were
      seen by the service over an 18-month period. Staphylococcus aureus was the most
      common isolate and central venous lines the most common source. Antibiotics were
      changed and additional investigations suggested in 62% and 61% of patients,
      respectively. The 30-day mortality was 19%. Implementation and delivery of the
      service over the 18-month study period cost pound 22,663 (pound 15,109 per year).
      The cost per change in antibiotic prescription was pound 244. The cost per 'near
      miss' detected was pound 1193. Overall mortality was no higher and possibly lower
      than in published studies. CONCLUSION: We believe that this model of care may be
      suitable for the management of patients with bacteraemia. A study assessing the
      cost-effectiveness of this approach is required.

PMID- 18805905
TI  - Multi-stringency wash of partially hybridized 60-mer probes reveals that the
      stringency along the probe decreases with distance from the microarray surface.
AB  - Here, we describe a multi-parametric study of DNA hybridization to probes with 20
      70% G + C content. Probes were designed towards 71 different sites/mutations in
      the phenylalanine hydroxylase gene. Seven probe lengths, three spacer lengths and
      six stringencies were systematically varied. The three spacer lengths were
      obtained by placing the gene-specific sequence in discrete steps along the 60-mer
      probes. The study was performed using Agilent 8 x 15 000 probes custom-made
      arrays and a home-built array washer providing different stringencies to each of
      the eight sub-arrays on the slides. Investigation of hybridization signals,
      specificity and dissociation curves indicated that probes close to the surface
      were influenced by an additional stringency provided by the microarray surface.
      Consistent with this, probes close to the surface required 4 x SSC, while probes
      placed away from the surface required 0.35 x SSC wash buffers in order to give
      accurate genotyping results. Multiple step dissociation was frequently observed
      for probes placed furthest away from surface, but not for probes placed proximal
      to the surface, which is consistent with the hypothesis that there is different
      stringency along the 60-mer. The results have impact on design of probes for
      genotyping, gene expression and comparative genome hybridization analysis.

PMID- 18805906
TI  - DiProDB: a database for dinucleotide properties.
AB  - DiProDB (http://diprodb.fli-leibniz.de) is a database of conformational and
      thermodynamic dinucleotide properties. It includes datasets both for DNA and RNA,
      as well as for single and double strands. The data have been shown to be
      important for understanding different aspects of nucleic acid structure and
      function, and they can also be used for encoding nucleic acid sequences. The
      database is intended to facilitate further applications of dinucleotide
      properties. A number of property datasets is highly correlated. Therefore, the
      database comes with a correlation analysis facility. Authors having determined
      new sets of dinucleotide property values are invited to submit these data to
      DiProDB.

PMID- 18805907
TI  - Mutagenicity of tamoxifen DNA adducts in human endometrial cells and in silico
      prediction of p53 mutation hotspots.
AB  - Tamoxifen elevates the risk of endometrial tumours in women and alpha-(N(2)
      deoxyguanosinyl)-tamoxifen adducts are reportedly present in endometrial tissue
      of patients undergoing therapy. Given the widespread use of tamoxifen there is
      considerable interest in elucidating the mechanisms underlying treatment
      associated cancer. Using a combined experimental and multivariate statistical
      approach we have examined the mutagenicity and potential consequences of adduct
      formation by reactive intermediates in target uterine cells. pSP189 plasmid
      containing the supF gene was incubated with alpha-acetoxytamoxifen or 4
      hydroxytamoxifen quinone methide (4-OHtamQM) to generate dG-N(2)-tamoxifen and dG
      N(2)-4-hydroxytamoxifen, respectively. Plasmids were replicated in Ishikawa cells
      then screened in Escherichia coli. Treatment with both alpha-acetoxytamoxifen and
      4-OHtamQM caused a dose-related increase in adduct levels, resulting in a damage
      dependent increase in mutation frequency for alpha-acetoxytamoxifen; 4-OHtamQM
      had no apparent effect. Only alpha-acetoxytamoxifen generated statistically
      different supF mutation spectra relative to the spontaneous pattern, with most
      mutations being GC-->TA transversions. Application of the LwPy53 algorithm to the
      alpha-acetoxytamoxifen spectrum predicted strong GC-->TA hotspots at codons 244
      and 273. These signature alterations do not correlate with current reports of the
      mutations observed in endometrial carcinomas from treated women, suggesting that
      dG-N(2)-tam adduct formation in the p53 gene is not a prerequisite for
      endometrial cancer initiation in women.

PMID- 18805908
TI  - Rigid spin-labeled nucleoside C: a nonperturbing EPR probe of nucleic acid
      conformation.
AB  - Rigid spin-labeled nucleoside C, an analog of deoxycytidine that base-pairs with
      deoxyguanosine, was incorporated into DNA oligomers by chemical synthesis.
      Thermal denaturation experiments and circular dichroism (CD) measurements showed
      that C has a negligible effect on DNA duplex stability and conformation.
      Nucleoside C was incorporated into several positions within single-stranded DNA
      oligomers that can adopt two hairpin conformations of similar energy, each of
      which contains a four-base loop. The relative mobility of nucleotides in the
      alternating C/G hairpin loops, 5'-d(GCGC) and 5'-d(CGCG), was determined by
      electron paramagnetic resonance (EPR) spectroscopy. The most mobile nucleotide in
      the loop is the second one from the 5'-end, followed by the third, first and
      fourth nucleotides, consistent with previous NMR studies of DNA hairpin loops of
      different sequences. The EPR hairpin data were also corroborated by fluorescence
      spectroscopy using oligomers containing reduced C (C(f)), which is fluorescent.
      Furthermore, EPR spectra of duplex DNAs that contained C at the end of the helix
      showed features that indicated dipolar coupling between two spins. These data are
      consistent with end-to-end duplex stacking in solution, which was only observed
      when G was paired to C, but not when C was paired with A, C or T.

PMID- 18805909
TI  - Involvement of Pinus taeda MYB1 and MYB8 in phenylpropanoid metabolism and
      secondary cell wall biogenesis: a comparative in planta analysis.
AB  - The involvement of two R2R3-MYB genes from Pinus taeda L., PtMYB1 and PtMYB8, in
      phenylpropanoid metabolism and secondary cell wall biogenesis was investigated in
      planta. These pine MYBs were constitutively overexpressed (OE) in Picea glauca
      (Moench) Voss, used as a heterologous conifer expression system. Morphological,
      histological, chemical (lignin and soluble phenols), and transcriptional
      analyses, i.e. microarray and reverse transcription quantitative PCR (RT-qPCR)
      were used for extensive phenotyping of MYB-overexpressing spruce plantlets. Upon
      germination of somatic embryos, root growth was reduced in both transgenics.
      Enhanced lignin deposition was also a common feature but ectopic secondary cell
      wall deposition was more strongly associated with PtMYB8-OE. Microarray and RT
      qPCR data showed that overexpression of each MYB led to an overlapping up
      regulation of many genes encoding phenylpropanoid enzymes involved in lignin
      monomer synthesis, while misregulation of several cell wall-related genes and
      other MYB transcription factors was specifically associated with PtMYB8-OE.
      Together, the results suggest that MYB1 and MYB8 may be part of a conserved
      transcriptional network involved in secondary cell wall deposition in conifers.

PMID- 18805910
TI  - A comparison of Dutch family doctors' and patients' perspectives on nutrition
      communication.
AB  - BACKGROUND: In recent years, we have investigated both patients' and family
      doctors' communicative characteristics towards nutrition communication in general
      practice with several qualitative and quantitative studies. A sound comparison of
      the survey results between both conversation partners has not been made before.
      OBJECTIVE: The aim of the present study was to put together data obtained by
      earlier studies for the first time in order to make comparisons of patients' and
      family doctors' communicative characteristics regarding nutrition communication.
      METHODS: In The Netherlands, 603 patients completed a face-to-face interview
      assisted questionnaire (65% response rate) and 267 family doctors completed a
      questionnaire (45% response rate). RESULTS: When comparing communicative
      characteristics, patients stronger believed that nutrition was an influence on
      health than family doctors. They also attributed a greater role to personal
      hygiene, stress and heredity, while family doctors were more convinced of the
      role of alcohol use and smoking on health. Patients more often rated their own
      nutrition knowledge as good than family doctors. In contrast, family doctors
      showed higher interest in nutrition and nutrition information than patients. As a
      result, a collinear model for family doctors and nutrition communication towards
      patients was provided. CONCLUSIONS: Significant differences between patients and
      family doctors were found for several communicative characteristics towards
      nutrition communication. It is important that family doctors become convinced
      that patients perceive them as a reliable and expert source of nutrition
      information. It is recommended that family doctors raise nutrition awareness
      among patients. Finally, we advise family doctors to pay attention to nutrition
      communication styles.

PMID- 18805911
TI  - Acylation stimulating protein but not complement C3 associates with metabolic
      syndrome components in Chinese children and adolescents.
AB  - OBJECTIVE: Childhood obesity is increasing worldwide and is increasingly
      associated with metabolic syndrome (MetS). Our aim was to examine acylation
      stimulating protein (ASP) and its precursor complement C3, in normal, overweight,
      and obese Chinese children and adolescents, and the relationships with body size,
      blood parameters, pubertal development, family environment, and MetS. METHODS:
      Children and adolescents (n=1603) from 6 to 18 years, boys (n=873) and girls
      (n=730), including normal weight (n=603), overweight (n=291) and obese (n=709)
      were assessed for body size parameters, pubertal development, blood lipids,
      glucose, insulin, ASP, and C3. RESULTS: ASP levels were increased in overweight
      and obese versus normal weight (P<0.001), while C3 showed little variation. This
      effect of overweight/obesity remained throughout early stages when boys and girls
      were separated by pubertal development or age, although age and pubertal status
      itself had no effect. Separation based on ASP quintiles demonstrated significant
      associations with blood cholesterol, triglyceride, low-density lipoprotein
      cholesterol (LDL-Chol), glucose, insulin, and homeostatic model assessment of
      insulin resistance in boys, and LDL-Chol, high-density lipoprotein cholesterol,
      and glucose in girls. A positive correlation with mother's body mass index in
      boys and girls (P=0.002 and P=0.014 respectively) as well as birth weight
      (P<0.001) was noted. MetS was strongly associated with increased ASP, the
      presence of a single MetS factor (especially hypertension, central obesity, or
      hyperglycemia) was associated with increased ASP. CONCLUSION: Changes in the
      plasma adipokine ASP in early obesity are associated with blood lipid and glucose
      modifications, family environment, and distinct MetS risk factors.

PMID- 18805912
TI  - Gender dimorphism in body composition abnormalities in acromegaly: males are more
      affected than females.
AB  - BACKGROUND: Acromegaly changes body composition (BC), but long-term gender
      differences have not been reported. OBJECTIVE: To evaluate BC in active and
      controlled acromegalic patients. DESIGN AND METHODS: Clinical and biochemical
      variables and BC (by dual-energy X-ray absorptiometry) were evaluated in 60
      acromegalic patients (19 active, 41 controlled) and 105 controls, matched for age
      and gender. RESULTS: Acromegalic males (n=24) had more total mass (89+/-13 vs
      76.5+/-15.3 kg, P<0.001), lean body mass (LBM; 64.6+/-8.7 vs 56.4+/-5.8 kg,
      P<0.001), and bone mineral content (BMC; 2.9+/-0.5 vs 2.6+/-0.3 kg, P<0.05) than
      controls (n=33). Controlled male patients (n=14) had more total mass (89+/-14.7
      vs 76.5+/-15.3 kg, P<0.05) and a trend to have more LBM (61.8+/-9.4 vs 56.4+/-5.8
      kg, P=0.065) than controls. Only in active disease was a decrease in fat mass
      (FM) observed, compared with controlled patients and controls (males: 19.5+/-5.3
      vs 27+/-6.2 and 25.9+/-4%, P<0.001; females: 30.3+/-6.7 vs 37.1+/-5.8 and 36.5+/
      6.6%, P<0.01). In females, no further differences were observed. No differences
      in BMC were found between eugonadal and hypogonadal acromegalic patients, but in
      hypogonadal females, acromegaly appeared to prevent the BMC loss seen in
      hypogonadal postmenopausal controls. GH and IGF1 levels were negatively
      correlated with FM (males, P<0.05; females, P<0.001), but in the regression
      analysis GH was a predictor of FM only in women. CONCLUSIONS: Control of
      acromegaly reverts decreased FM in both genders; only in males more total mass
      and a trend for more LBM persist. The anabolic effect of GH on bone reverted in
      cured males, but persisted in females and appeared to override the bone loss of
      menopause.

PMID- 18805913
TI  - Androgen receptor CAG repeat polymorphism is associated with serum testosterone
      levels, obesity and serum leptin in men with type 2 diabetes.
AB  - OBJECTIVE: To determine the relationships between androgen receptor CAG repeat
      polymorphism length (AR CAG), sex hormones and clinical variables in men with
      type 2 diabetes (DM2). Men with DM2 are known to have a high prevalence of low
      testosterone levels. Studies suggest that testosterone replacement therapy may
      improve insulin sensitivity and glycaemic control in men with DM2 and reduces
      central obesity and serum leptin. AR CAG is known to correlate negatively with AR
      sensitivity and positively with body fat, insulin levels, and leptin in healthy
      men. DESIGN: Cross-sectional study set in a district general hospital diabetes
      centre. METHODS: Sex hormones, AR CAG and symptoms of hypogonadism were assessed
      in 233 men with DM2. Associations were sought between these variables and others
      such as obesity, leptin, glycaemic control, and blood pressure. RESULTS:
      Testosterone was negatively associated and AR CAG positively associated with
      obesity and leptin. The associations of AR CAG with leptin and obesity were
      independent of testosterone, estradiol, gonadotropins, and age. AR CAG was also
      independently associated with total, bioavailable and free testosterone, LH,
      waist circumference, body mass index, leptin, and systolic blood pressure. There
      was no association of AR CAG with sex hormone binding globulin, estradiol,
      HbA(1C) or the symptoms of hypogonadism. CONCLUSIONS: The association of longer
      AR CAG with obesity and leptin suggests that shorter AR CAG may have an influence
      in maintaining healthy anthropomorphics and metabolism in men with DM2.
      Testosterone and LH levels are higher in men with longer AR CAG, probably
      reflecting reduced negative feedback through a less sensitive receptor.

PMID- 18805914
TI  - Retesting the childhood-onset GH-deficient patient.
AB  - GH deficiency (GHD) in adults has to be shown by a single provocative test,
      provided that it is validated. Insulin tolerance test (ITT) has been indicated as
      the test of choice; now also glucagon test is validated and represents an
      alternative. The GHRH plus arginine (ARG) test and testing with GHRH plus a GH
      secretagogue are equally reliable diagnostic tools, and are now considered as
      'golden' standards as ITT. Childhood-onset (CO) GHD needs retesting in late
      adolescence or young adulthood; this is a major clinical challenge and raises
      questions about the most appropriate method and cut-off value. Appropriate re
      evaluation of GH status is represented by simple measurement of IGF1
      concentration off rhGH treatment. Clearly, low IGF1 levels are evidence of
      persistent severe GHD in subjects with genetic GHD or panhypopituitarism.
      However, normal IGF1 levels never rule out severe GHD and CO-GHD with normal IGF1
      levels must undergo a provocative test. The appropriate GH cut-off limit is
      specific for each provocative test. As shown by the ROC curve analysis, in late
      adolescents and young adults, the lowest normal GH peak response to ITT is 6.1
      microg/l while that to GHRH+ARG test is 19.0 microg/l. These cut-off limits,
      however, are just indicative as being variable as a function of the assay used.
      No other test is validated for retesting. As GHRH+ARG test mostly explores the GH
      releasable pool, normal GH response would be verified by a second ITT in order to
      rule out subtle hypothalamic defect.

PMID- 18805915
TI  - Multiple endocrine neoplasia type 2A in two families with the familial medullary
      thyroid carcinoma associated G533C mutation of the RET proto-oncogene.
AB  - INTRODUCTION: Multiple endocrine neoplasia type 2A (MEN2A) is an autosomal
      dominant hereditary disorder, associated with a cluster of germline gain-of
      function mutations of the RET proto-oncogene (RET), mainly in exons 10-15. The
      G533C mutation in exon 8 of the RET is rare and has been mainly related to the
      familial medullary thyroid carcinoma. PATIENTS-METHODS: We describe the RET G533C
      mutation in exon 8 of the RET in two unrelated female index patients, with MEN2A
      phenotype, consisting of pheochromocytoma which was the presenting feature and
      medullary thyroid carcinoma. In addition, 12 family members were also studied.
      DNA extraction, PCR, and sequencing of RET was performed in exons 7-19 and 21,
      following standard procedures. RESULTS: The mutation was found in both index
      patients and in 6 out of 12 family members (50%). Three of them were
      biochemically affected with histologically proven medullary thyroid carcinoma in
      two of them while there are no certain clues regarding the other three members as
      they declined further evaluation. CONCLUSION: Patients with MEN2A should be also
      searched in exon 8 while positive carriers of this mutation should be screened
      annually for pheochromocytoma or other components of the syndrome.

PMID- 18805916
TI  - Insulin resistance and obesity in childhood.
AB  - Childhood obesity is a significant health problem that has reached epidemic
      proportions around the world and is associated with several metabolic and
      cardiovascular complications. Insulin resistance is a common feature of childhood
      obesity and is considered to be an important link between adiposity and the
      associated risk of type 2 diabetes and cardiovascular disease. Insulin resistance
      is also a key component of the metabolic syndrome, and its prevalence in the
      paediatric population is increasing, particularly among obese children and
      adolescents. Several factors are implicated in the pathogenesis of obesity
      related insulin resistance, such as increased free fatty acids and many hormones
      and cytokines released by adipose tissue. Valid and reliable methods are
      essential to assess the presence and the extent of insulin resistance, the
      associated risk factors and the effect of pharmacological and lifestyle
      interventions. The two most common tests to assess insulin resistance are the
      hyperinsulinemic euglycemic clamp and the frequently sampled i.v. glucose
      tolerance test utilizing the minimal model. However, both these tests are not
      easily accomplished, are time consuming, expensive and invasive. Simpler methods
      to assess insulin resistance based on surrogate markers derived from an oral
      glucose tolerance test or from fasting insulin and glucose levels have been
      validated in children and adolescents and widely used. Given the strong
      association between obesity, insulin resistance and the development of metabolic
      syndrome and cardiovascular disease, prevention and treatment of childhood
      obesity appear to be essential to prevent the development of insulin resistance
      and the associated complications.

PMID- 18805917
TI  - Hypothyroidism in patients with pseudohypoparathyroidism type Ia: clinical
      evidence of resistance to TSH and TRH.
AB  - OBJECTIVE: Hypothyroidism is a manifestation of multi-hormonal resistance in
      pseudohypoparathyroidism type Ia (PHP Ia). The objective of the study was to
      determine the mechanisms of hypothyroidism in PHP Ia. DESIGN: A prospective
      study. PATIENTS: Ten patients with PHP Ia. MEASUREMENTS: The serum concentrations
      of TSH, free triiodothyronine (FT(3)), free thyroxine (FT(4)), and prolactin
      (PRL) were measured at baseline and after stimulation with TRH (200 microg i.v).
      RESULTS: The median basal serum TSH concentration was 4.92 mU/l. Basal serum TSH
      concentration was slightly elevated in eight patients (4.22-7.0 mU/l; normal
      range, 0.4-3.6 mU/l), normal in one patient (2.5 mU/l), and high in one patient
      (13.1 mU/l). After the TRH test, TSH concentrations increased to 13.4-36.0 mU/l
      (normal range, 4.0-20.0 mU/l). The absolute values after the test were normal in
      three patients and high in seven patients. However, TSH responses relative to the
      baseline value (stimulated/basal TSH and expressed as a fold increase), which
      reflect the relative increases after TRH stimulation, were low in seven patients
      (2.3- to 4.3-fold TSH) and normal in three patients. Basal FT(4) concentration
      was normal in seven patients and low in three patients (range, 8.4-20.0 pmol/l;
      mean, 14.1+/-4.3 pmol/l; normal range, 10.5-23.0 pmol/l). Basal FT(3)
      concentration was normal in nine patients and low in one patient (range, 0.9-5.0
      pmol/l; mean, 3.8+/-1.1 pmol/l; normal range, 3.3-6.1 pmol/l). FT(4) and FT(3)
      were not significantly increased after the TRH test. PRL concentration was normal
      at baseline and increased from 7 to 96 ng/ml after TRH. CONCLUSION: Our results
      support the hypothesis that patients with PHP Ia have impaired sensitivity to
      both TSH and TRH.

PMID- 18805918
TI  - High resolution approach to the native state ensemble kinetics and
      thermodynamics.
AB  - Many biologically interesting functions such as allosteric switching or protein
      ligand binding are determined by the kinetics and mechanisms of transitions
      between various conformational substates of the native basin of globular
      proteins. To advance our understanding of these processes, we constructed a two
      dimensional free energy surface (FES) of the native basin of a small globular
      protein, Trp-cage. The corresponding order parameters were defined using two
      native substructures of Trp-cage. These calculations were based on extensive
      explicit water all-atom molecular dynamics simulations. Using the obtained two
      dimensional FES, we studied the transition kinetics between two Trp-cage
      conformations, finding that switching process shows a borderline behavior between
      diffusive and weakly-activated dynamics. The transition is well-characterized
      kinetically as a biexponential process. We also introduced a new one-dimensional
      reaction coordinate for the conformational transition, finding reasonable
      qualitative agreement with the two-dimensional kinetics results. We investigated
      the distribution of all the 38 native nuclear magnetic resonance structures on
      the obtained FES, analyzing interactions that stabilize specific low-energy
      conformations. Finally, we constructed a FES for the same system but with simple
      dielectric model of water instead of explicit water, finding that the results
      were surprisingly similar in a small region centered on the native conformations.
      The dissimilarities between the explicit and implicit model on the larger-scale
      point to the important role of water in mediating interactions between amino acid
      residues.

PMID- 18805919
TI  - Probing the lipid membrane dipole potential by atomic force microscopy.
AB  - The electrostatic properties of biological membranes can be described by three
      parameters: the transmembrane potential, the membrane surface potential, and the
      membrane dipole potential. The first two are well characterized in terms of their
      magnitudes and biological effects. The dipole potential, however, is not well
      characterized. Various methods to measure the membrane dipole potential
      indirectly yield different values, and there is not even agreement on the source
      of the membrane dipole moment. This ambiguity impedes investigations into the
      biological effects of the membrane dipole moment, which should be substantial
      considering the large interfacial fields with which it is associated.
      Electrostatic analysis of phosphatidylcholine lipid membranes with the atomic
      force microscope reveals a repulsive force between the negatively charged probe
      tips and the zwitterionic lipids. This unexpected interaction has been analyzed
      quantitatively to reveal that the repulsion is due to a weak external field
      created by the internal membrane dipole potential. The analysis yields a dipole
      moment of 1.5 Debye per lipid with a dipole potential of +275 mV for supported
      phosphatidylcholine membranes. This new ability to quantitatively measure the
      membrane dipole moment in a noninvasive manner with nanometer scale spatial
      resolution will be useful in identifying the biological effects of the dipole
      potential.

PMID- 18805920
TI  - Alternative versions of the myosin relay domain differentially respond to load to
      influence Drosophila muscle kinetics.
AB  - We measured the influence of alternative versions of the Drosophila melanogaster
      myosin heavy chain relay domain on muscle mechanical properties. We exchanged
      relay domain regions (encoded by alternative versions of exon 9) between an
      embryonic (EMB) isoform and the indirect flight muscle isoform (IFI) of myosin.
      Previously, we observed no effect of exchanging the EMB relay domain region into
      the flight muscle isoform (IFI-9b) on in vitro actin motility velocity or
      solution ATPase measurements compared to IFI. However, in indirect flight muscle
      fibers, IFI-9b exhibited decreased maximum power generation (P(max)) and optimal
      frequency of power generation (f(max)) to 70% and 83% of IFI fiber values. The
      decrease in muscle performance reduced the flight ability and wing-beat frequency
      of IFI-9b Drosophila compared to IFI Drosophila. Previously, we found that
      exchanging the flight muscle specific relay domain into the EMB isoform (EMB-9a)
      prevented actin movement in the in vitro motility assay compared to EMB, which
      does support actin movement. However, in indirect flight muscle fibers EMB-9a was
      a highly effective motor, increasing P(max) and f(max) 2.5-fold and 1.4-fold,
      respectively, compared to fibers expressing EMB. We propose that the oscillatory
      load EMB-9a experiences in the muscle fiber reduces a high activation energy
      barrier between two strongly bound states of the cross-bridge cycle, thereby
      promoting cross-bridge cycling. The IFI relay domain's enhanced sensitivity to
      load increases cross-bridge kinetics, whereas the EMB version is less load
      sensitive.

PMID- 18805921
TI  - Characterization of protein dynamics in asymmetric cell division by scanning
      fluorescence correlation spectroscopy.
AB  - The development and differentiation of complex organisms from the single
      fertilized egg is regulated by a variety of processes that all rely on the
      distribution and interaction of proteins. Despite the tight regulation of these
      processes with respect to temporal and spatial protein localization, exact
      quantification of the underlying parameters, such as concentrations and
      distribution coefficients, has so far been problematic. Recent experiments
      suggest that fluorescence correlation spectroscopy on a single molecule level in
      living cells has great promise in revealing these parameters with high precision.
      The optically challenging situation in multicellular systems such as embryos can
      be ameliorated by two-photon excitation, where scattering background and
      cumulative photobleaching is limited. A more severe problem is posed by the large
      range of molecular mobilities observed at the same time, as standard FCS relies
      strongly on the presence of mobility-induced fluctuations. In this study, we
      overcame the limitations of standard FCS. We analyzed in vivo polarity protein
      PAR-2 from eggs of Caenorhabditis elegans by beam-scanning FCS in the cytosol and
      on the cortex of C. elegans before asymmetric cell division. The surprising
      result is that the distribution of PAR-2 is largely uncoupled from the movement
      of cytoskeletal components of the cortex. These results call for a more
      systematic future investigation of the different cortical elements, and show that
      the FCS technique can contribute to answering these questions, by providing a
      complementary approach that can reveal insights not obtainable by other
      techniques.

PMID- 18805922
TI  - Analysis of molecular concentration and brightness from fluorescence fluctuation
      data with an electron multiplied CCD camera.
AB  - We demonstrate the calculation of particle brightness and concentration from
      fluorescence-fluctuation photon-counting statistics using an electron-multiplied
      charge-coupled device (EMCCD) camera. This technique provides a concentration
      independent measure of particle brightness in dynamic systems. The high
      sensitivity and highly parallel detection of EMCCD cameras allow for imaging of
      dynamic particle brightness, providing the capability to follow aggregation
      reactions in real time. A critical factor of the EMCCD camera is the presence of
      nonlinearity at high intensities. These nonlinearities arise due to limited
      capacity of the CCD well and to the analog-to-digital converter maximum range.
      However, we show that the specific camera we used (with a 16-bit analog-to
      digital converter) has sufficient dynamic range for most microscopy applications.
      In addition, we explore the importance of camera timing behavior as it is
      affected by the vertical frame transfer speed of the camera. Although the camera
      has microsecond exposure time for illumination of a few pixels, the exposure time
      increased to milliseconds for full-field illumination. Finally, we demonstrate
      the ability of the technique to follow concentration changes and measure single
      molecule brightness in real time in living cells.

PMID- 18805923
TI  - Molecular dynamics simulation and coarse-grained analysis of the Arp2/3 complex.
AB  - A molecular dynamics investigation and coarse-grained analysis of inactivated
      actin-related protein (Arp) 2/3 complex is presented. It was found that the
      nucleotide binding site within Arp3 remained in a closed position with bound ATP
      or ADP, but opened when simulation with no nucleotide was performed. In contrast,
      simulation of the isolated Arp3 subunit with bound ATP, showed a fast opening of
      the nucleotide binding cleft. A homology model for the missing subdomains 1 and 2
      of Arp2 was constructed, and it was also found that the Arp2 binding cleft
      remained closed with bound nucleotide. Within the nucleotide binding cleft a
      distinct opening and closing period of 10 ns was observed in many of the
      simulations of Arp2/3 as well as isolated Arp3. Substitution studies were
      employed, and several alanine substitutions were found to induce a partial
      opening of the ATP binding cleft in Arp3 and Arp2, whereas only a single
      substitution was found to induce opening of the ADP binding cleft. It was also
      found that the nucleotide type did not cause a substantial change on interfacial
      contacts between Arp3 and the ArpC2, ArpC3 and ArpC4 subunits. Nucleotide-free
      Arp3 had generally less stable contacts, but the overall contact architecture was
      constant. Finally, nucleotide-dependent coarse-grained models for Arp3 are
      developed that serve to further highlight the structural differences induced in
      Arp3 by nucleotide hydrolysis.

PMID- 18805924
TI  - A mutation in CFTR modifies the effects of the adenylate kinase inhibitor Ap5A on
      channel gating.
AB  - Mutations in the gene that encodes the cystic fibrosis transmembrane conductance
      regulator (CFTR) cause cystic fibrosis. The CFTR anion channel is controlled by
      ATP binding and enzymatic activity at the two nucleotide-binding domains. CFTR
      exhibits two types of enzymatic activity: 1), ATPase activity in the presence of
      ATP and 2), adenylate kinase activity in the presence of ATP plus physiologic
      concentrations of AMP or ADP. Previous work showed that P(1),P(5)-di(adenosine
      5')pentaphosphate (Ap(5)A), a specific adenylate kinases inhibitor, inhibited
      wild-type CFTR. In this study, we report that Ap(5)A increased activity of CFTR
      with an L1254A mutation. This mutation increased the EC50 for ATP by >10-fold and
      reduced channel activity by prolonging the closed state. Ap(5)A did not elicit
      current on its own nor did it alter ATP EC50 or maximal current. However, it
      changed the relationship between ATP concentration and current. At submaximal ATP
      concentrations, Ap(5)A stimulated current by stabilizing the channel open state.
      Whereas previous work indicated that adenylate kinase activity regulated channel
      opening, our data suggest that Ap(5)A binding may also influence channel closing.
      These results also suggest that a better understanding of the adenylate kinase
      activity of CFTR may be of value in developing new therapeutic strategies for
      cystic fibrosis.

PMID- 18805925
TI  - Gap junction coupling and calcium waves in the pancreatic islet.
AB  - The pancreatic islet is a highly coupled, multicellular system that exhibits
      complex spatiotemporal electrical activity in response to elevated glucose
      levels. The emergent properties of islets, which differ from those arising in
      isolated islet cells, are believed to arise in part by gap junctional coupling,
      but the mechanisms through which this coupling occurs are poorly understood. To
      uncover these mechanisms, we have used both high-speed imaging and theoretical
      modeling of the electrical activity in pancreatic islets under a reduction in the
      gap junction mediated electrical coupling. Utilizing islets from a gap junction
      protein connexin 36 knockout mouse model together with chemical inhibitors, we
      can modulate the electrical coupling in the islet in a precise manner and
      quantify this modulation by electrophysiology measurements. We find that after a
      reduction in electrical coupling, calcium waves are slowed as well as disrupted,
      and the number of cells showing synchronous calcium oscillations is reduced. This
      behavior can be reproduced by computational modeling of a heterogeneous
      population of beta-cells with heterogeneous levels of electrical coupling. The
      resulting quantitative agreement between the data and analytical models of islet
      connectivity, using only a single free parameter, reveals the mechanistic
      underpinnings of the multicellular behavior of the islet.

PMID- 18805926
TI  - Mechanism of KCl enhancement in detection of nonionic polymers by nanopore
      sensors.
AB  - The mechanisms of KCl-induced enhancement in identification of individual
      molecules of poly(ethylene glycol) using solitary alpha-hemolysin nanoscale pores
      are described. The interaction of single molecules with the nanopore causes
      changes in the ionic current flowing through the pore. We show that the on-rate
      constant of the process is several hundred times larger and that the off-rate is
      several hundred times smaller in 4 M KCl than in 1 M KCl. These shifts
      dramatically improve detection and make single molecule identification feasible.
      KCl also changes the solubility of poly(ethylene glycol) by the same order of
      magnitude as it changes the rate constants. In addition, the polymer-nanopore
      interaction is determined to be a strong non-monotonic function of voltage,
      indicating that the flexible, nonionic poly(ethylene glycol) acts as a charged
      molecule. Therefore, salting-out and Coulombic interactions are responsible for
      the KCl-induced enhancement. These results will advance the development of
      devices with sensor elements based on single nanopores.

PMID- 18805927
TI  - The Gaussian curvature elastic energy of intermediates in membrane fusion.
AB  - The Gaussian curvature elastic energy contribution to the energy of membrane
      fusion intermediates has usually been neglected because the Gaussian curvature
      elastic modulus, kappa, was unknown. It is now possible to measure kappa for
      phospholipids that form bicontinuous inverted cubic (Q(II)) phases. Here, it is
      shown that one can estimate kappa for lipids that do not form Q(II) phases by
      studying the phase behavior of lipid mixtures. The method is used to estimate
      kappa for several lipid compositions in excess water. The values of kappa are
      used to compute the curvature elastic energies of stalks and catenoidal fusion
      pores according to recent models. The Gaussian curvature elastic contribution is
      positive and similar in magnitude to the bending energy contribution: it
      increases the total curvature energy of all the fusion intermediates by 100 units
      of k(B)T or more. It is important to note that this contribution makes the
      predicted intermediate energies compatible with observed lipid phase behavior in
      excess water. An order-of-magnitude fusion rate equation is used to estimate
      whether the predicted stalk energies are consistent with the observed rates of
      stalk-mediated processes in pure lipid systems. The current theory predicts a
      stalk energy that is slightly too large, by approximately 30 k(B)T, to
      rationalize the observed rates of stalk-mediated processes in
      phosphatidylethanolamine or N-monomethylated dioleoylphosphatidylethanolamine
      systems. Despite this discrepancy, the results show that models of fusion
      intermediate energy are accurate enough to make semiquantitative predictions
      about how proteins mediate biomembrane fusion. The same rate model shows that for
      proteins to drive biomembrane fusion at observed rates, they have to perform
      mediating functions corresponding to a reduction in the energy of a purely
      lipidic stalk by several tens of k(B)T. By binding particular peptide sequences
      to the monolayer surface, proteins could lower fusion intermediate energies by
      altering the elastic constants of the patches of lipid monolayer that form the
      stalk. Here, it is shown that if peptide binding changes kappa or some other
      combinations of local elastic constants by only tens of percents, the stalk
      energy and the energy of catenoidal fusion pores would decrease by tens of k(B)T
      relative to the pure lipid value. This is comparable to the required mediating
      effect. The curvature energies of stalks and catenoidal fusion pores have almost
      the same dependence on monolayer elastic constants as the curvature energies of
      the rhombohedral and Q(II) phases; respectively. The effects of isolated fusion
      relevant peptides on the energies of these intermediates can be determined by
      studying the effects of the peptides on the stability of rhombohedral and Q(II)
      phases.

PMID- 18805928
TI  - Breaking the 200 nm limit for routine flow linear dichroism measurements using UV
      synchrotron radiation.
AB  - The first synchrotron radiation flow linear dichroism spectra are reported. High
      quality spectral data can be collected from 450 nm down to 180 nm in contrast to
      the practical cutoff of approximately 200 nm on benchtop instruments. State-of
      the-art microvolume capillary Couette flow linear dichroism was successfully
      ported to a synchrotron radiation source. The sample volume required is < 50
      microL. A characterization of the synchrotron radiation linear dichroism with
      known DNA and DNA-ligand systems is presented and the viability of the setup
      confirmed. Typically, wavelengths down to 180 nm are now routinely accessible
      with a high signal/noise ratio with little limitation from the sample
      concentration. The 180 nm cutoff is due to the quartz of the Couette cell rather
      than the beamline itself. We show the application of the simultaneous
      determination of the sample absorption spectrum to calculate the reduced linear
      dichroism signal. Spectra for calf thymus DNA, DNA/ethidium bromide, and DNA/4',6
      diamidino-2-phenylindole systems illustrate the quality of data that can be
      obtained.

PMID- 18805929
TI  - Slow stress propagation in adherent cells.
AB  - Mechanical cues influence a wide range of cellular behaviors including motility,
      differentiation, and tumorigenesis. Although previous studies elucidated the role
      of specific players such as ion channels and focal adhesions as local
      mechanosensors, the investigation of how mechanical perturbations propagate
      across the cell is necessary to understand the spatial coordination of cellular
      processes. Here we quantify the magnitude and timing of intracellular stress
      propagation, using atomic force microscopy and particle tracking by defocused
      fluorescence microscopy. The apical cell surface is locally perturbed by atomic
      force microscopy cantilever indentation, and distal displacements are measured in
      three dimensions by tracking integrin-bound fluorescent particles. We observe an
      immediate response and slower equilibration, occurring over times that increase
      with distance from perturbation. This distance-dependent equilibration occurs
      over several seconds and can be eliminated by disruption of the actin
      cytoskeleton. Our experimental results are not explained by traditional
      viscoelastic models of cell mechanics, but they are consistent with predictions
      from poroelastic models that include both cytoskeletal deformation and flow of
      the cytoplasm. Our combined atomic force microscopy-particle tracking
      measurements provide direct evidence of slow, distance-dependent dissipative
      stress propagation in response to external mechanical cues and offer new insights
      into mechanical models and physiological behaviors of adherent cells.

PMID- 18805930
TI  - Dynamic organization of gene loci and transcription compartments in the cell
      nucleus.

PMID- 18805931
TI  - Probing the dynamic organization of transcription compartments and gene loci
      within the nucleus of living cells.
AB  - The three-dimensional organization of nuclear compartments within living cells
      determines genome function and yet their underlying self-organizing principles
      are unclear. We visualize in real-time transcriptionally active compartments
      (TCs) by the transient enrichment of fluorescently-labeled uridine 5'
      triphosphate molecules within living cells. These TCs partially colocalize with
      active RNA-Pol II in the cell nucleus. Fluorescence anisotropy maps of chromatin
      compaction evidences a more open chromatin structure at the TCs. Using live-cell
      timelapse imaging, heterogeneity in the dynamic behavior of TCs has been revealed
      which falls into three distinct classes: subdiffusive, super-diffusive, and
      normal diffusive behavior. In contrast, the mobility of a candidate gene locus,
      either in the repressed or activated state, undergoes a differential restricted
      motion that is coupled to TC movement. Further TC dynamics is directly affected
      by small molecule chromatin structure modulators and adenosine triphosphate
      depletion. This heterogeneous behavior in TC dynamics within living cells could
      provide an interesting paradigm to explore the spatiotemporal dimension to gene
      transcription control.

PMID- 18805932
TI  - Azide as a probe of proton transfer reactions in photosynthetic oxygen evolution.
AB  - In oxygenic photosynthesis, photosystem II (PSII) is the multisubunit membrane
      protein responsible for the oxidation of water to O2 and the reduction of
      plastoquinone to plastoquinol. One electron charge separation in the PSII
      reaction center is coupled to sequential oxidation reactions at the oxygen
      evolving complex (OEC), which is composed of four manganese ions and one calcium
      ion. The sequentially oxidized forms of the OEC are referred to as the S(n)
      states. S(1) is the dark-adapted state of the OEC. Flash-induced oxygen
      production oscillates with period four and occurs during the S(3) to S(0)
      transition. Chloride plays an important, but poorly understood role in
      photosynthetic water oxidation. Chloride removal is known to block manganese
      oxidation during the S(2) to S(3) transition. In this work, we have used azide as
      a probe of proton transfer reactions in PSII. PSII was sulfate-treated to deplete
      chloride and then treated with azide. Steady state oxygen evolution measurements
      demonstrate that azide inhibits oxygen evolution in a chloride-dependent manner
      and that azide is a mixed or noncompetitive inhibitor. This result is consistent
      with two azide binding sites, one at which azide competes with chloride and one
      at which azide and chloride do not compete. At pH 7.5, the K(i) for the competing
      site was estimated as 1 mM, and the K(i)' for the uncompetitive site was
      estimated as 8 mM. Vibrational spectroscopy was then used to monitor
      perturbations in the frequency and amplitude of the azide antisymmetric
      stretching band. These changes were induced by laser-induced charge separation in
      the PSII reaction center. The results suggest that azide is involved in proton
      transfer reactions, which occur before manganese oxidation, on the donor side of
      chloride-depleted PSII.

PMID- 18805933
TI  - Versatile analysis of single-molecule tracking data by comprehensive testing
      against Monte Carlo simulations.
AB  - We propose here an approach for the analysis of single-molecule trajectories
      which is based on a comprehensive comparison of an experimental data set with
      multiple Monte Carlo simulations of the diffusion process. It allows quantitative
      data analysis, particularly whenever analytical treatment of a model is
      infeasible. Simulations are performed on a discrete parameter space and compared
      with the experimental results by a nonparametric statistical test. The method
      provides a matrix of p-values that assess the probability for having observed the
      experimental data at each setting of the model parameters. We show the testing
      approach for three typical situations observed in the cellular plasma membrane:
      i), free Brownian motion of the tracer, ii), hop diffusion of the tracer in a
      periodic meshwork of squares, and iii), transient binding of the tracer to slowly
      diffusing structures. By plotting the p-value as a function of the model
      parameters, one can easily identify the most consistent parameter settings but
      also recover mutual dependencies and ambiguities which are difficult to determine
      by standard fitting routines. Finally, we used the test to reanalyze previous
      data obtained on the diffusion of the glycosylphosphatidylinositol-protein CD59
      in the plasma membrane of the human T24 cell line.

PMID- 18805934
TI  - Reaction of the Co(II)-substrate radical pair catalytic intermediate in coenzyme
      B12-dependent ethanolamine ammonia-lyase in frozen aqueous solution from 190 to
      217 K.
AB  - The decay kinetics of the aminoethanol-generated Co(II)-substrate radical pair
      catalytic intermediate in ethanolamine ammonia-lyase from Salmonella typhimurium
      have been measured on timescales of <10(5) s in frozen aqueous solution from 190
      to 217 K. X-band continuous-wave electron paramagnetic resonance (EPR)
      spectroscopy of the disordered samples has been used to continuously monitor the
      full radical pair EPR spectrum during progress of the decay after temperature
      step reaction initiation. The decay to a diamagnetic state is complete and no
      paramagnetic intermediate states are detected. The decay exhibits three kinetic
      regimes in the measured temperature range, as follows. i), Low temperature range,
      190 < or = T < or = 207 K: the decay is biexponential with constant fast (0.57 +/
      0.04) and slow (0.43 +/- 0.04) phase amplitudes. ii), Transition temperature
      range, 207 < T < 214 K: the amplitude of the slow phase decreases to zero with a
      compensatory rise in the fast phase amplitude, with increasing temperature. iii),
      High temperature range, T > or = 214 K: the decay is monoexponential. The
      observed first-order rate constants for the monoexponential (k(obs,m)) and the
      fast phase of the biexponential decay (k(obs,f)) adhere to the same linear
      relation on an lnk versus T(-1) (Arrhenius) plot. Thus, k(obs,m) and k(obs,f)
      correspond to the same apparent Arrhenius prefactor and activation energy
      (logA(app,f) (s(-1)) = 13.0, E(a,app,f) = 15.0 kcal/mol), and therefore, a common
      decay mechanism. We propose that k(obs,m) and k(obs,f) represent the native,
      forward reaction of the substrate through the radical rearrangement step. The
      slow phase rate constant (k(obs,s)) for 190 < or = T < or = 207 K obeys a
      different linear Arrhenius relation (logA(app,s) (s(-1)) = 13.9, E(a,app,s) =
      16.6 kcal/mol). In the transition temperature range, k(obs,s) displays a super
      Arrhenius increase with increasing temperature. The change in E(a,app,s) with
      temperature and the narrow range over which it occurs suggest an origin in a
      liquid/glass or dynamical transition. A discontinuity in the activation barrier
      for the chemical reaction is not expected in the transition temperature range.
      Therefore, the transition arises from a change in the properties of the protein.
      We propose that a protein dynamical contribution to the reaction, which is
      present above the transition temperature, is lost below the transition
      temperature, owing to an increase in the activation energy barrier for protein
      motions that are coupled to the reaction. For both the fast and slow phases of
      the low temperature decay, the dynamical transition in protein motions that are
      obligatorily coupled to the reaction of the Co(II)-substrate radical pair lies
      below 190 K.

PMID- 18805935
TI  - Characterizing aqueous solution conformations of a peptide backbone using Raman
      optical activity computations.
AB  - Mounting spectroscopic evidence indicates that alanine predominantly adopts
      extended polyproline II (PPII) conformations in short polypeptides. Here we
      analyze Raman optical activity (ROA) spectra of N-acetylalanine-N'-methylamide
      (Ala dipeptide) in H2O and D2O using density functional theory on Monte Carlo
      (MC) sampled geometries to examine the propensity of Ala dipeptide to adopt
      compact right-handed (alpha(R)) and left-handed (alpha(L)) helical conformations.
      The computed ROA spectra based on MC-sampled alpha(R) and PPII peptide
      conformations contain all the key spectral features found in the measured
      spectra. However, there is no significant similarity between the measured and
      computed ROA spectra based on the alpha(L)- and beta-conformations sampled by the
      MC methods. This analysis suggests that Ala dipeptide populates the alpha(R) and
      PPII conformations but no substantial population of alpha(L)- or beta-structures,
      despite sampling alpha(L)- and beta-structures in our MC simulations. Thus, ROA
      spectra combined with the theoretical analysis allow us to determine the dominant
      populated structures. Including explicit solute-solvent interactions in the
      theoretical analysis is essential for the success of this approach.

PMID- 18805936
TI  - Structural dynamics of the actomyosin complex probed by a bifunctional spin label
      that cross-links SH1 and SH2.
AB  - We have used a bifunctional spin label (BSL) to cross-link Cys(707) (SH1) and
      Cys(697) (SH2) in the catalytic domain of myosin subfragment 1 (S1). BSL induces
      the same weakened ATPase activity and actin-binding affinity that is observed
      when SH1 and SH2 are cross-linked with pPDM, which traps an analog of the post
      hydrolysis state A.M.ADP.P. Electron paramagnetic resonance showed that BSL
      reports the global orientation and dynamics of S1. When bound to actin in
      oriented muscle fibers in the absence of ATP, BSL-S1 showed almost complete
      orientational disorder, as reported previously for the weakly bound A.M.ADP. In
      contrast, helical order is observed for the strongly bound state A.M. Saturation
      transfer electron paramagnetic resonance showed that the disorder of cross-linked
      S1 on actin is nearly static on the microsecond timescale, at least 30 times
      slower than that of A.M.ADP. We conclude that cross-linked S1 exhibits rotational
      disorder comparable to that of A.M.ADP, slow rotational mobility comparable to
      that of A.M, and intermediate actin affinity. These results support the
      hypothesis that the catalytic domain of myosin is orientationally disordered on
      actin in a post-hydrolysis state in the early stages of force generation.

PMID- 18805937
TI  - Structure-function relationships in the mineralocorticoid receptor.
AB  - The signature action of aldosterone in the regulation of electrolyte and fluid
      balance is well established. However, the role of aldosterone as an important
      contributor to morbidity and mortality in heart failure has gained a heightened
      interest in recent years, but the mechanisms of this action are not well
      understood. Aldosterone is the principal physiological ligand for the
      mineralocorticoid receptor (MR), a ligand-activated transcription factor, that
      also binds to the physiological glucocorticoid, cortisol. Both classes of
      hormones bind with similar affinity to the MR, but the molecular basis of
      selective and tissue-specific effects of MR ligands is not yet fully documented.
      The structural and functional determinants of MR function are described and their
      significance is discussed.

PMID- 18805938
TI  - Tryptophan mutations at azi-etomidate photo-incorporation sites on alpha1 or
      beta2 subunits enhance GABAA receptor gating and reduce etomidate modulation.
AB  - The potent general anesthetic etomidate produces its effects by enhancing GABA(A)
      receptor activation. Its photolabel analog [(3)H]azi-etomidate labels residues
      within transmembrane domains on alpha and beta subunits: alphaMet236 and
      betaMet286. We hypothesized that these methionines contribute to etomidate sites
      formed at alpha-beta subunit interfaces and that increasing side-chain bulk and
      hydrophobicity at either locus would mimic etomidate binding and block etomidate
      effects. Channel activity was electrophysiologically quantified in
      alpha(1)beta(2)gamma(2L) receptors with alpha(1)M236W or beta(2)M286W mutations,
      in both the absence and the presence of etomidate. Measurements included
      spontaneous activation, GABA EC(50), etomidate agonist potentiation, etomidate
      direct activation, and rapid macrocurrent kinetics. Both alpha(1)M236W and
      beta(2)M286W mutations induced spontaneous channel opening, lowered GABA EC(50),
      increased maximal GABA efficacy, and slowed current deactivation, mimicking
      effects of etomidate on alpha(1)beta(2)gamma(2L) channels. These changes were
      larger with alpha(1)M236W than with beta(2)M286W. Etomidate (3.2 muM) reduced
      GABA EC(50) much less in alpha(1)M236Wbeta(2)gamma(2L) receptors (2-fold) than in
      wild type (23-fold). However, etomidate was more potent and efficacious in
      directly activating alpha(1)M236Wbeta(2)gamma(2L) compared with wild type. In
      alpha(1)beta(2)M286Wgamma(2L) receptors, etomidate induced neither agonist
      potentiation nor direct channel activation. These results support the hypothesis
      that alpha(1)Met236 and beta(2)Met286 are within etomidate sites that
      allosterically link to channel gating. Although alpha(1)M236W produced the larger
      impact on channel gating, beta(2)M286W produced more profound changes in
      etomidate sensitivity, suggesting a dominant role in drug binding. Furthermore,
      quantitative mechanistic analysis demonstrated that wild-type and mutant results
      are consistent with the presence of only one class of etomidate sites mediating
      both agonist potentiation and direct activation.

PMID- 18805939
TI  - Functional genetic polymorphisms and female reproductive disorders: part II-
      endometriosis.
AB  - BACKGROUND: Endometriosis has a strong genetic component, and numerous genetic
      studies have been reported. METHODS: We have systematically reviewed these
      studies and included 114 in our final selection. RESULTS: We found no consistent
      evidence linking endometriosis with specific polymorphisms in genes encoding
      inflammatory mediators, proteins involved in sex steroid metabolism, vascular
      function and tissue remodelling. Although a number of polymorphisms have been
      associated with endometriosis in selected populations, the associations have not
      been independently confirmed, either because only single studies were carried out
      on these markers/genes or because other studies reported no association. The most
      solid evidence linking specific polymorphisms to endometriosis came from studies
      investigating glutathione-S-transferase, a phase II detoxification enzyme.
      Carriage of the GSTT1 null deletion variant showed consistent association with
      endometriosis with a 29% increased risk; however, it cannot be excluded that this
      result was due to publication bias, and this association should be independently
      confirmed in large-scale, well-designed case-control studies. CONCLUSIONS: The
      evidence of an association between genetic polymorphisms and endometriosis is
      weak. Carriage of the GSTT1 null deletion may moderately increase the risk of
      this disease. We suggest that the methodology of association studies should be
      improved in order to identify and validate associations in endometriosis.

PMID- 18805940
TI  - Problems associated with the use of thyrogen in patients with a thyroid gland.

PMID- 18805941
TI  - Clinical assessment of autism in high-risk 18-month-olds.
AB  - Earlier intervention improves outcomes for children with autism spectrum
      disorders (ASDs), but existing identification tools are at the limits of
      standardization with 18-month-olds. We assessed potential behavioural markers of
      ASD at 18 months in a high-risk cohort of infant siblings of children with ASD.
      Prospective data were collected using the Autism Diagnostic Observation Schedule
      (ADOS) and Autism Observation Scale for Infants (AOSI) on 155 infant siblings and
      73 low-risk controls at 18 months. Infants were classified into three groups (ASD
      sibs, non-ASD sibs, controls) based on blind best-estimate diagnosis at age 3.
      Fisher's exact tests, followed by discriminant function analyses, revealed that
      the majority of informative ADOS items came from the social and behavioural
      domains, and AOSI items measuring behavioural reactivity and motor control
      contributed additional information. Findings highlight the importance of
      considering not only social-communication deficits, but also basic dimensions of
      temperament including state regulation and motor control when assessing toddlers
      with suspected ASD.

PMID- 18805942
TI  - Atypical object exploration at 12 months of age is associated with autism in a
      prospective sample.
AB  - This prospective study examined object exploration behavior in 66 12-month-old
      infants, of whom nine were subsequently diagnosed with an autism spectrum
      disorder. Previous investigations differ on when the repetitive behaviors
      characteristic of autism are first present in early development. A task was
      developed that afforded specific opportunities for a range of repetitive uses of
      objects and was coded blind to outcome status. The autism/ASD outcome group
      displayed significantly more spinning, rotating, and unusual visual exploration
      of objects than two comparison groups. The average unusual visual exploration
      score of the autism/ASD group was over four standard deviations above the mean of
      the group with no concerns at outcome. Repetitive behaviors at 12 months were
      significantly related to cognitive and symptomatic status at 36 month outcome.
      These results suggest that repetitive or stereotyped behaviors may be present
      earlier than initially thought in very young children developing the autism
      phenotype.

PMID- 18805943
TI  - Visual disengagement in the infant siblings of children with an autism spectrum
      disorder (ASD).
AB  - Children with autism spectrum disorders (ASDs) are impaired in visually
      disengaging attention in both social and non-social contexts. These impairments
      may, in subtler form, also affect the infant siblings of children with ASD (ASD
      sibs). We investigated patterns of visual attention (gazing) in 6-month-old ASD
      sibs (n=17) and the siblings of typically developing children (COMP-sibs: n=17)
      during the Face-to-Face/Still-Face Protocol (FFSF), in which parents are
      sequentially responsive, non-responsive, and responsive to their infants.
      Throughout the protocol, ASD-sibs shifted their gaze to and from their parents'
      faces less frequently than did COMP-sibs. The mean durations of ASD-sibs' gazes
      away from their parents' faces were longer than those of COMP-sibs. ASD-sibs and
      COMP-sibs did not differ in the mean durations of gazes at their parents' faces.
      In sum, ASD-sibs showed no deficits in visual interest to their parents' faces,
      but greater interest than COMP-sibs in non-face stimuli.

PMID- 18805944
TI  - Validation of the Infant-Toddler Checklist as a broadband screener for autism
      spectrum disorders from 9 to 24 months of age.
AB  - There is an urgent requirement for the improvement of early detection of ASDs.
      This article provides a brief review of research on the accuracy of screeners for
      children with ASD that have been administered to general pediatric samples and
      then present results of a population-based study with a broadband screener to
      detect children with communication delays including children with ASD.

PMID- 18805945
TI  - Screening for autism in older and younger toddlers with the Modified Checklist
      for Autism in Toddlers.
AB  - The Modified Checklist for Autism in Toddlers (M-CHAT) was used to screen younger
      (16-23 months) versus older (24-30 months) high- and low-risk toddlers. Refusal
      rates for follow-up interview showed no group differences, but parents of
      younger/low-risk children were more likely to refuse evaluation than parents of
      high-risk children. PPP for an ASD diagnosis was: younger/high-risk 0.79,
      older/high-risk 0.74, younger/low-risk 0.28, and older/low-risk 0.61, with PPP
      differing by age within the low-risk group. Most of the children in all groups,
      however, were diagnosed with a developmental disorder. Symptom severity generally
      did not differ among groups. Cognitive and adaptive measures showed minimal group
      differences. Therefore, older and younger toddlers had similar symptomatology and
      developmental delays; PPP for ASD is better at 24 than 18 months for low-risk
      children; however, these children are still highly likely to show a developmental
      disorder. Clinical decision making should balance early identification against
      the lower specificity of M-CHAT screening for the younger/low-risk group.

PMID- 18805946
TI  - Screening for autism spectrum disorders in primary care settings.
AB  - The need for autism-specific screening during pediatric well-child visits has
      been established. However, additional support for specific screening instruments
      is needed. The current study used the Modified Checklist for Autism in Toddlers
      (M-CHAT) and the M-CHAT Follow-Up Interview to screen 4797 children during
      toddler checkups. Of the 4797 cases, 466 screened positive on the M-CHAT; of the
      362 who completed the follow-up interview, 61 continued to show risk for autism
      spectrum disorders (ASDs). A total of 41 children have been evaluated; 21
      children have been diagnosed with ASD, 17 were classified with non-ASD delays,
      and three were typically developing. The PPV of M-CHAT plus interview was .57. It
      is notable that only four of the 21 cases of ASD were flagged by their
      pediatrician. These findings suggest that the M-CHAT is effective in identifying
      ASD in primary care settings. Future research will follow this sample
      longitudinally.

PMID- 18805947
TI  - Use of the Screening Tool for Autism in Two-Year-Olds (STAT) for children under
      24 months: an exploratory study.
AB  - The study examined the properties of the Screening Tool for Autism in Two-Year
      Olds (STAT) for children under 24 months. The STAT provides a standard context
      for observing social-communicative behavior in play, imitation, and
      communication. Seventy-one children received the STAT between 12 and 23 months of
      age and a follow-up diagnostic evaluation after 24 months. All had an older
      sibling with an autism spectrum diagnosis (n=59) or had been referred for
      evaluation for concerns about autism (n=12). Signal detection analysis resulted
      in a cut score of 2.75 for this sample, which yielded a sensitivity of 0.95,
      specificity of 0.73, positive predictive value of 0.56, and negative predictive
      value of 0.97. False positives were highest for the 12- to 13-month-old age
      group; STAT screening properties were improved when the sample was limited to
      children 14 months and older. Implications for using the STAT with children under
      24 months are discussed.

PMID- 18805948
TI  - Reaction to diagnosis and parenting styles among mothers of young children with
      ASDs.
AB  - When a child is diagnosed with an autism spectrum disorder (ASD) parents often
      experience a range of difficult feelings, which typically are not addressed in
      child-focused interventions. This study examined the relationship between a
      mother's acceptance of and sense of resolution regarding her child's diagnosis of
      an ASD and maternal interaction style, controlling for child competence, autism
      symptoms and maternal depression. Participants included 63 children with an ASD
      between 20 and 50 months of age and their mothers. Mothers who were more
      emotionally resolved were rated as higher in Cognitive Engagement and Supportive
      Engagement in play interactions, reflecting greater verbal and nonverbal
      scaffolding to enhance the child's play and attention to activities and greater
      reciprocity and mutual enjoyment. This study highlights the importance of
      considering a mother's resolution about her child's diagnosis, suggesting that
      maternal emotions and cognitions associated with the diagnosis may be potential
      targets for intervention.

PMID- 18805949
TI  - High glycolate oxidase activity is required for survival of maize in normal air.
AB  - A mutant in the maize (Zea mays) Glycolate Oxidase1 (GO1) gene was characterized
      to investigate the role of photorespiration in C4 photosynthesis. An Activator
      induced allele of GO1 conditioned a seedling lethal phenotype when homozygous and
      had 5% to 10% of wild-type GO activity. Growth of seedlings in high CO2 (1%-5%)
      was sufficient to rescue the mutant phenotype. Upon transfer to normal air, the
      go1 mutant became necrotic within 7 d and plants died within 15 d. Providing [1
      14C]glycolate to leaf tissue of go1 mutants in darkness confirmed that the
      substrate is inefficiently converted to 14CO2, but both wild-type and GO
      deficient mutant seedlings metabolized [1-14C]glycine similarly to produce
      [14C]serine and 14CO2 in a 1:1 ratio, suggesting that the photorespiratory
      pathway is otherwise normal in the mutant. The net CO2 assimilation rate in wild
      type leaves was only slightly inhibited in 50% O2 in high light but decreased
      rapidly and linearly with time in leaves with low GO. When go1 mutants were
      shifted from high CO2 to air in light, they accumulated glycolate linearly for 6
      h to levels 7-fold higher than wild type and 11-fold higher after 25 h. These
      studies show that C4 photosynthesis in maize is dependent on photorespiration
      throughout seedling development and support the view that the carbon oxidation
      pathway evolved to prevent accumulation of toxic glycolate.

PMID- 18805950
TI  - Alterations in cytosolic glucose-phosphate metabolism affect structural features
      and biochemical properties of starch-related heteroglycans.
AB  - The cytosolic pools of glucose-1-phosphate (Glc-1-P) and glucose-6-phosphate are
      essential intermediates in several biosynthetic paths, including the formation of
      sucrose and cell wall constituents, and they are also linked to the cytosolic
      starch-related heteroglycans. In this work, structural features and biochemical
      properties of starch-related heteroglycans were analyzed as affected by the
      cytosolic glucose monophosphate metabolism using both source and sink organs from
      wild-type and various transgenic potato (Solanum tuberosum) plants. In leaves,
      increased levels of the cytosolic phosphoglucomutase (cPGM) did affect the
      cytosolic heteroglycans, as both the glucosyl content and the size distribution
      were diminished. By contrast, underexpression of cPGM resulted in an unchanged
      size distribution and an unaltered or even increased glucosyl content of the
      heteroglycans. Heteroglycans prepared from potato tubers were found to be similar
      to those from leaves but were not significantly affected by the level of cPGM
      activity. However, external glucose or Glc-1-P exerted entirely different effects
      on the cytosolic heteroglycans when added to tuber discs. Glucose was directed
      mainly toward starch and cell wall material, but incorporation into the
      constituents of the cytosolic heteroglycans was very low and roughly reflected
      the relative monomeric abundance. By contrast, Glc-1-P was selectively taken up
      by the tuber discs and resulted in a fast increase in the glucosyl content of the
      heteroglycans that quantitatively reflected the level of the cytosolic
      phosphorylase activity. Based on (14)C labeling experiments, we propose that in
      the cytosol, glucose and Glc-1-P are metabolized by largely separated paths.

PMID- 18805951
TI  - Transcriptional profiling of mature Arabidopsis trichomes reveals that NOECK
      encodes the MIXTA-like transcriptional regulator MYB106.
AB  - Leaf hairs (trichomes) of Arabidopsis (Arabidopsis thaliana) have been
      extensively used as a model to address general questions in cell and
      developmental biology. Here, we lay the foundation for a systems-level
      understanding of the biology of this model cell type by performing genome-wide
      gene expression analyses. We have identified 3,231 genes that are up-regulated in
      mature trichomes relative to leaves without trichomes, and we compared wild-type
      trichomes with two mutants, glabra3 and triptychon, that affect trichome
      morphology and physiology in contrasting ways. We found that cell wall-related
      transcripts were particularly overrepresented in trichomes, consistent with their
      highly elaborated structure. In addition, trichome expression maps revealed high
      activities of anthocyanin, flavonoid, and glucosinolate pathways, indicative of
      the roles of trichomes in the biosynthesis of secondary compounds and defense.
      Interspecies comparisons revealed that Arabidopsis trichomes share many expressed
      genes with cotton (Gossypium hirsutum) fibers, making them an attractive model to
      study industrially important fibers. In addition to identifying physiological
      processes involved in the development of a specific cell type, we also
      demonstrated the utility of transcript profiling for identifying and analyzing
      regulatory gene function. One of the genes that are differentially expressed in
      fibers is the MYB transcription factor GhMYB25. A combination of transcript
      profiling and map-based cloning revealed that the NOECK gene of Arabidopsis
      encodes AtMYB106, a MIXTA-like transcription factor and homolog of cotton
      GhMYB25. However, in contrast to Antirrhinum, in which MIXTA promotes epidermal
      cell outgrowth, AtMYB106 appears to function as a repressor of cell outgrowth in
      Arabidopsis.

PMID- 18805952
TI  - Impact of PsbTc on forward and back electron flow, assembly, and phosphorylation
      patterns of photosystem II in tobacco.
AB  - Photosystem II (PSII) of oxygen-evolving cyanobacteria, algae, and land plants
      mediates electron transfer from the Mn(4)Ca cluster to the plastoquinone pool. It
      is a dimeric supramolecular complex comprising more than 30 subunits per monomer,
      of which 16 are bitopic or peripheral, low-molecular-weight components. Directed
      inactivation of the plastid gene encoding the low-molecular-weight peptide PsbTc
      in tobacco (Nicotiana tabacum) does not prevent photoautotrophic growth. Mutant
      plants appear normal green, and levels of PSII proteins are not affected. Yet,
      PSII-dependent electron transport, stability of PSII dimers, and assembly of PSII
      light-harvesting complexes (LHCII) are significantly impaired. PSII light
      sensitivity is moderately increased and recovery from photoinhibition is delayed,
      leading to faster D1 degradation in DeltapsbTc under high light.
      Thermoluminescence emission measurements revealed alterations of midpoint
      potentials of primary/secondary electron-accepting plastoquinone of PSII
      interaction. Only traces of CP43 and no D1/D2 proteins are phosphorylated,
      presumably due to structural changes of PSII in DeltapsbTc. In striking contrast
      to the wild type, LHCII in the mutant is phosphorylated in darkness, consistent
      with its association with PSI, indicating an increased pool of reduced
      plastoquinone in the dark. Finally, our data suggest that the secondary electron
      accepting plastoquinone of PSII site, the properties of which are altered in
      DeltapsbTc, is required for oxidation of reduced plastoquinone in darkness in an
      oxygen-dependent manner. These data present novel aspects of plastoquinone redox
      regulation, chlororespiration, and redox control of LHCII phosphorylation.

PMID- 18805953
TI  - Perturbed lignification impacts tree growth in hybrid poplar--a function of sink
      strength, vascular integrity, and photosynthetic assimilation.
AB  - The effects of reductions in cell wall lignin content, manifested by RNA
      interference suppression of coumaroyl 3'-hydroxylase, on plant growth, water
      transport, gas exchange, and photosynthesis were evaluated in hybrid poplar trees
      (Populus alba x grandidentata). The growth characteristics of the reduced lignin
      trees were significantly impaired, resulting in smaller stems and reduced root
      biomass when compared to wild-type trees, as well as altered leaf morphology and
      architecture. The severe inhibition of cell wall lignification produced trees
      with a collapsed xylem phenotype, resulting in compromised vascular integrity,
      and displayed reduced hydraulic conductivity and a greater susceptibility to wall
      failure and cavitation. In the reduced lignin trees, photosynthetic carbon
      assimilation and stomatal conductance were also greatly reduced, however, shoot
      xylem pressure potential and carbon isotope discrimination were higher and water
      use efficiency was lower, inconsistent with water stress. Reductions in
      assimilation rate could not be ascribed to increased stomatal limitation. Starch
      and soluble sugars analysis of leaves revealed that photosynthate was
      accumulating to high levels, suggesting that the trees with substantially reduced
      cell wall lignin were not carbon limited and that reductions in sink strength
      were, instead, limiting photosynthesis.

PMID- 18805954
TI  - MAP20, a microtubule-associated protein in the secondary cell walls of hybrid
      aspen, is a target of the cellulose synthesis inhibitor 2,6-dichlorobenzonitrile.
AB  - We have identified a gene, denoted PttMAP20, which is strongly up-regulated
      during secondary cell wall synthesis and tightly coregulated with the secondary
      wall-associated CESA genes in hybrid aspen (Populus tremula x tremuloides).
      Immunolocalization studies with affinity-purified antibodies specific for
      PttMAP20 revealed that the protein is found in all cell types in developing xylem
      and that it is most abundant in cells forming secondary cell walls. This PttMAP20
      protein sequence contains a highly conserved TPX2 domain first identified in a
      microtubule-associated protein (MAP) in Xenopus laevis. Overexpression of
      PttMAP20 in Arabidopsis (Arabidopsis thaliana) leads to helical twisting of
      epidermal cells, frequently associated with MAPs. In addition, a PttMAP20-yellow
      fluorescent protein fusion protein expressed in tobacco (Nicotiana tabacum)
      leaves localizes to microtubules in leaf epidermal pavement cells. Recombinant
      PttMAP20 expressed in Escherichia coli also binds specifically to in vitro
      assembled, taxol-stabilized bovine microtubules. Finally, the herbicide 2,6
      dichlorobenzonitrile, which inhibits cellulose synthesis in plants, was found to
      bind specifically to PttMAP20. Together with the known function of cortical
      microtubules in orienting cellulose microfibrils, these observations suggest that
      PttMAP20 has a role in cellulose biosynthesis.

PMID- 18805955
TI  - Distinct roles for Khd1p in the localization and expression of bud-localized
      mRNAs in yeast.
AB  - The RNA-binding protein Khd1p (KH-domain protein 1) is required for efficient
      localization of ASH1 mRNA to the bud-tip, probably acting as a translational
      repressor during mRNA transport in yeast. Here, we have systematically examined
      Khd1p mRNA targets and colocalization with known bud-tip-localized mRNAs in vivo.
      Affinity purification and DNA microarray analysis of Khd1p-associated mRNAs
      revealed hundreds of potential mRNAs targets, many of them encoding membrane
      associated proteins. The putative targets include the messages for MID2, MTL1,
      WSC2, SRL1, EGT2, CLB2, ASH1, and Khd1p colocalizes with these mRNAs at the bud
      tip. The combination of bioinformatics, RNA localization, and in vitro RNA
      binding assays revealed that Khd1p binds to CNN repeats in coding regions of mRNA
      targets. Among the proteins encoded by previously known bud-tip-localized mRNAs,
      only Mtl1p levels were decreased in khd1Delta mutant cells, whereas Ash1p and
      Srl1p were reduced in cells overexpressing KHD1. Hence, Khd1p differentially
      affects gene expression possibly due to combinatorial arrangement with additional
      factors reflecting the redundant structure of post-transcriptional regulatory
      systems.

PMID- 18805956
TI  - Effects of distension on airway inflammation and venular P-selectin expression.
AB  - We previously have shown in mice and rats, enhanced leukocyte recruitment to
      airway postcapillary venules after excessive distention imposed by the
      application of positive end-expiratory pressure. Because P-selectin was shown to
      be essential for this outcome, we sought to establish an in vitro endothelial
      cell model and determine the mechanisms whereby mechanical distension alters
      adhesion molecule expression. P-selectin surface expression on mouse jugular vein
      endothelial cells exposed to cyclic stretch (5 or 20% elongation for 5 min;
      Flexercell) were compared with static cells. The larger, pathophysiological
      regimen of cyclic stretch showed a 54% increase in P-selectin expression after
      stretch compared with static cells. This response was attenuated but confirmed in
      tracheal venular endothelium (29% increase). We questioned whether these changes
      were dependent on increases in intracellular Ca(2+) through voltage-gated Ca(2+)
      channels. The stretch-induced increase in P-selectin expression was substantially
      decreased by pretreatment with the T-type Ca(2+) channel inhibitor mibefradil
      (76% inhibition). Furthermore, when the Ca(v)3.1 T-type Ca(2+) channel expression
      was decreased in both endothelial cell subtypes with specific small-interfering
      RNA, the distension-induced expression of P-selectin decreased to levels less
      than that observed in static cells. We conclude that P-selectin expression on
      systemic venular endothelial cells contributes to a proinflammatory phenotype
      after mechanical stretch and can be selectively modulated by voltage-gated
      calcium channel inhibition.

PMID- 18805957
TI  - Lubiprostone activates non-CFTR-dependent respiratory epithelial chloride
      secretion in cystic fibrosis mice.
AB  - Periciliary fluid balance is maintained by the coordination of sodium and
      chloride channels in the apical membranes of the airways. In the absence of the
      cystic fibrosis transmembrane regulator (CFTR), chloride secretion is diminished
      and sodium reabsorption exaggerated. ClC-2, a pH- and voltage-dependent chloride
      channel, is present on the apical membranes of airway epithelial cells. We
      hypothesized that ClC-2 agonists would provide a parallel pathway for chloride
      secretion. Using nasal potential difference (NPD) measurements, we quantified
      lubiprostone-mediated Cl(-) transport in sedated cystic fibrosis null (gut
      corrected), C57Bl/6, and A/J mice during nasal perfusion of lubiprostone (a
      putative ClC-2 agonist). Baseline, amiloride-inhibited, chloride-free gluconate
      substituted Ringer with amiloride and low-chloride Ringer plus lubiprostone (at
      increasing concentrations of lubiprostone) were perfused, and the NPD was
      continuously recorded. A clear dose-response relationship was detected in all
      murine strains. The magnitude of the NPD response to 20 muM lubiprostone was -5.8
      +/- 2.1 mV (CF, n = 12), -8.1 +/- 2.6 mV (C57Bl/6 wild-type, n = 12), and -5.3 +/
      1.2 mV (AJ wild-type, n = 8). A cohort of ClC-2 knockout mice did not respond to
      20 muM lubiprostone (n = 6, P = 0.27). In C57Bl/6 mice, inhibition of CFTR with
      topical application of CFTR inhibitor-172 did not abolish the lubiprostone
      response, thus confirming the response seen is independent of CFTR regulation. RT
      PCR confirmed expression of ClC-2 mRNA in murine lung homogenate. The direct
      application of lubiprostone in the CF murine nasal airway restores nearly normal
      levels of chloride secretion in nasal epithelia.

PMID- 18805958
TI  - Mechanical stretch decreases migration of alveolar epithelial cells through
      mechanisms involving Rac1 and Tiam1.
AB  - Mechanical ventilation can overdistend the lungs or generate shear forces in them
      during repetitive opening/closing, contributing to lung injury and inflammation
      in patients with acute respiratory distress syndrome (ARDS). Repair of the
      injured lung epithelium is important for restoring normal barrier and lung
      function. In the current study, we investigated the effects of cyclic mechanical
      strain (CS), constant distention strain (CD), and simulated positive end
      expiratory pressure (PEEP) on activation of Rac1 and wound closure of rat primary
      alveolar type 2 (AT2) cells. Cyclic stretch inhibited the migration of wounded
      AT2 cells in a dose-dependent manner with no inhibition occurring with 5% CS, but
      significant inhibition with 10% and 15% CS. PEEP conditions were investigated by
      stretching AT2 cells to 15% maximum strain (at a frequency of 10 cycles/min) with
      relaxation to 10% strain. AT2 cells were also exposed to 20% CD. All three types
      of mechanical strain inhibited wound closure of AT2 cells compared with static
      controls. Since lamellipodial extensions in migrating cells at the wound edge
      were significantly smaller in stretched cells, we measured Rac1 activity and
      found it to be decreased in stretched cells. We also demonstrate that Tiam1, a
      Rac1-specific guanine nucleotide exchange factor, was expressed mainly in the
      cytosol of AT2 cells exposed to mechanical strain compared with membrane
      localization in static cells. Downregulation of Tiam1 with 100 microM NSC-23766
      inhibited activation of Rac1 and migration of AT2 cells, suggesting its
      involvement in repair mechanisms of AT2 cells subjected to mechanical strain.

PMID- 18805959
TI  - Effects of melatonin in an experimental model of ventilator-induced lung injury.
AB  - Melatonin is a free radical scavenger and a broad-spectrum antioxidant and has
      well-documented immunomodulatory effects. We studied the effects of this hormone
      on lung damage, oxidative stress, and inflammation in a model of ventilator
      induced lung injury (VILI), using 8- to 12-wk-old Swiss mice (n = 48). Animals
      were randomized into three experimental groups: control (not ventilated); low
      pressure ventilation [peak inspiratory pressure 15 cmH(2)O, positive end
      expiratory pressure (PEEP) 2 cmH(2)O], and high-pressure ventilation (peak
      inspiratory pressure 25 cmH(2)O, PEEP 0 cmH(2)O). Each group was divided into two
      subgroups: eight animals were treated with melatonin (10 mg/kg ip, 30 min before
      the onset of ventilation) and the remaining eight with vehicle. After 2 h of
      ventilation, lung injury was evaluated by gas exchange, wet-to-dry weight ratio,
      and histological analysis. Levels of malondialdehyde, glutathione peroxidase,
      interleukins IL-1beta, IL-6, TNF-alpha, and IL-10, and matrix metalloproteinases
      2 and 9 in lung tissue were measured as indicators of oxidation status, pro-/anti
      inflammatory cytokines, and matrix turnover, respectively. Ventilation with high
      pressures induced severe lung damage and release of TNF-alpha, IL-6, and matrix
      metalloproteinase-9. Treatment with melatonin improved oxygenation and decreased
      histological lung injury but significantly increased oxidative stress quantified
      by malondialdehyde levels. There were no differences in TNF-alpha, IL-1beta, IL
      6, or matrix metalloproteinases caused by melatonin treatment, but IL-10 levels
      were significantly higher in treated animals. These results suggest that
      melatonin decreases VILI by increasing the anti-inflammatory response despite an
      unexpected increase in oxidative stress.

PMID- 18805960
TI  - Integrin-linked kinase regulates smooth muscle differentiation marker gene
      expression in airway tissue.
AB  - Phenotypic changes in airway smooth muscle occur with airway inflammation and
      asthma. These changes may be induced by alterations in the extracellular matrix
      that initiate signaling pathways mediated by integrin receptors. We hypothesized
      that integrin-linked kinase (ILK), a multidomain protein kinase that binds to the
      cytoplasmic tail of beta-integrins, may be an important mediator of signaling
      pathways that regulate the growth and differentiation state of airway smooth
      muscle. We disrupted signaling pathways mediated by ILK in intact differentiated
      tracheal muscle tissues by depleting ILK protein using ILK antisense. The
      depletion of ILK protein increased the expression of the smooth muscle
      differentiation marker genes myosin heavy chain (SmMHC), SM22alpha, and calponin
      and increased the expression of SmMHC protein. Conversely, the overexpression of
      ILK protein reduced the mRNA levels of SmMHC, SM22alpha, and calponin and SmMHC
      protein. Analysis by chromatin immunoprecipitation showed that the binding of the
      transcriptional regulator serum response factor (SRF) to the promoters of SmMHC,
      SM22alpha, and calponin genes was increased in ILK-depleted tissues and decreased
      in tissues overexpressing ILK. ILK depletion also increased the amount of SRF
      that localized within the nucleus. ILK depletion and overexpression,
      respectively, decreased and increased the activation of its downstream substrate
      protein kinase B (PKB/Akt). The pharmacological inhibition of Akt activity also
      increased SRF binding to the promoters of smooth muscle-specific genes and
      increased expression of smooth muscle proteins, suggesting that ILK may exert its
      effects by regulating the activity of Akt. We conclude that ILK is a critical
      regulator of airway smooth muscle differentiation. ILK may mediate signals from
      integrin receptors that control airway smooth muscle differentiation in response
      to alterations in the extracellular matrix.

PMID- 18805961
TI  - Endoglin expression in blood and endothelium is differentially regulated by
      modular assembly of the Ets/Gata hemangioblast code.
AB  - Endoglin is an accessory receptor for TGF-beta signaling and is required for
      normal hemangioblast, early hematopoietic, and vascular development. We have
      previously shown that an upstream enhancer, Eng -8, together with the promoter
      region, mediates robust endothelial expression yet is inactive in blood. To
      identify hematopoietic regulatory elements, we used array-based methods to
      determine chromatin accessibility across the entire locus. Subsequent transgenic
      analysis of candidate elements showed that an endothelial enhancer at Eng +9 when
      combined with an element at Eng +7 functions as a strong hemato-endothelial
      enhancer. Chromatin immunoprecipitation (ChIP)-chip analysis demonstrated
      specific binding of Ets factors to the promoter as well as to the -8, +7+9
      enhancers in both blood and endothelial cells. By contrast Pu.1, an Ets factor
      specific to the blood lineage, and Gata2 binding was only detected in blood.
      Gata2 was bound only at +7 and GATA motifs were required for hematopoietic
      activity. This modular assembly of regulators gives blood and endothelial cells
      the regulatory freedom to independently fine-tune gene expression and emphasizes
      the role of regulatory divergence in driving functional divergence.

PMID- 18805962
TI  - Clinical and molecular predictors of thrombocytopenia and risk of bleeding in
      patients with von Willebrand disease type 2B: a cohort study of 67 patients.
AB  - Type 2B von Willebrand disease (VWD2B) is caused by an abnormal von Willebrand
      factor (VWF) with increased affinity for the platelet receptor glycoprotein Ib
      alpha (GPIb-alpha) that may result in moderate to severe thrombocytopenia. We
      evaluated the prevalence and clinical and molecular predictors of
      thrombocytopenia in a cohort of 67 VWD2B patients from 38 unrelated families
      characterized by VWF mutations. Platelet count, mean platelet volume, and
      morphologic evaluations of blood smear were obtained at baseline and during
      physiologic (pregnancy) or pathologic (infections, surgeries) stress conditions.
      Thrombocytopenia was found in 20 patients (30%) at baseline and in 38 (57%) after
      stress conditions, whereas platelet counts were always normal in 16 patients
      (24%) from 5 families carrying the P1266L/Q or R1308L mutations. VWF in its GPIb
      alpha-binding conformation (VWF-GPIb-alpha/BC) was higher than normal in all
      except the 16 cases without thrombocytopenia (values up to 6-fold higher than
      controls). The risk of bleeding was higher in patients with thrombocytopenia
      (adjusted hazard ratio = 4.57; 95% confidence interval, 1.17-17.90) and in those
      with the highest tertile of bleeding severity score (5.66; 95% confidence
      interval, 1.03-31.07). Prediction of possible thrombocytopenia in VWD2B by
      measuring VWF-GPIb-alpha/BC is important because a low platelet count is an
      independent risk factor for bleeding.

PMID- 18805963
TI  - Pharmacokinetics, pharmacodynamics, efficacy, and safety of a new recombinant
      asparaginase preparation in children with previously untreated acute
      lymphoblastic leukemia: a randomized phase 2 clinical trial.
AB  - The pharmacokinetics, pharmacodynamics, efficacy, and safety of a new recombinant
      Escherichia coli-asparaginase preparation was compared with Asparaginase medac.
      Thirty-two children with acute lymphoblastic leukemia were randomized to receive
      one of both agents at a dose of 5000 U/m(2) every 3 days, for a total of 8 doses
      during induction treatment. The serum activity-time profile after the first dose
      of recombinant asparaginase was similar to that of Asparaginase medac. The trough
      serum activities were greater than the desired threshold of 100 U/L in both
      treatment groups. Asparagine was completely depleted in serum and in
      cerebrospinal fluid, whereas glutamine levels were only moderately influenced. No
      significant difference between the 2 treatments regarding the degree of
      asparagine depletion, duration of depletion, complete remission rate, and minimal
      residual disease status at the end of induction, overall frequency or intensity
      of adverse events was seen. Observed adverse reactions are known as possible and
      labeled side effects of asparaginase treatment and chemotherapy. We conclude that
      the new recombinant asparaginase and other native Asparaginase medac are
      bioequivalent and have the same pharmacodynamic effects and the same direct
      toxicity profile in children with acute lymphoblastic leukemia. This trial was
      registered at http://www.controlled-trials.com as no. ISRCTN 75734403.

PMID- 18805964
TI  - NF-kappaB1 and c-Rel cooperate to promote the survival of TLR4-activated B cells
      by neutralizing Bim via distinct mechanisms.
AB  - The nuclear factor-kappaB (NF-kappaB) pathway is crucial for the survival of B
      cells stimulated through Toll-like receptors (TLRs). Here, we show that the
      heightened death of TLR4-activated nfkb1(-/-) B cells is the result of a failure
      of the Tpl(2)/MEK/ERK pathway to phosphorylate the proapo-ptotic BH3-only protein
      Bim and target it for degradation. ERK inactivation of Bim after TLR4 stimulation
      is accompanied by an increase in A1/Bim and Bcl-x(L)/Bim complexes that we
      propose represents a c-Rel-dependent mechanism for neutralizing Bim. Together
      these findings establish that optimal survival of TLR4-activated B cells depends
      on the NF-kappaB pathway neutralizing Bim through a combination of Bcl-2
      prosurvival protein induction and Tpl2/ERK-dependent Bim phosphorylation and
      degradation.

PMID- 18805965
TI  - How I treat rare venous thromboses.
AB  - Venous thromboembolism may involve venous sites other than the lower limbs, such
      as cerebral, splanchnic, and upper limb veins. Although uncommon, these
      thromboses may be clinically severe and challenging for caregivers. In this
      review, the main pathogenic, clinical, and therapeutic features of thromboses in
      rare venous sites are discussed. Even though there was a lot of recent progress
      in understanding the mechanistic role of inherited and acquired thrombophilia and
      of the interactions between different risk factors, the optimal management of
      these patients is still unsettled, being currently based on the consensus of
      experts due to the lack of randomized trials. The implementation of large
      interdisciplinary registries is a necessary weapon to optimize the treatment of
      rare venous diseases.

PMID- 18805966
TI  - Dendritic cell microvilli: a novel membrane structure associated with the
      multifocal synapse and T-cell clustering.
AB  - Polarizing effects of productive dendritic cell (DC)-T-cell interactions on DC
      cytoskeleton have been known in some detail, but the effects on DC membrane have
      been studied to a lesser extent. We found that T-cell incubation led to DC
      elongation and segregation of characteristic DC veils to the broader pole of the
      cell. On the opposite DC pole, we observed a novel membrane feature in the form
      of bundled microvilli. Each villus was approximately 100 nm in diameter and 600
      to 1200 nm long. Microvilli exhibited high density of antigen-presenting
      molecules and costimulatory molecules and provided the physical basis for the
      multifocal immune synapse we observed during human DC and T-cell interactions. T
      cells preferentially bound to this site in clusters often contained both CD4(+)
      and CD8(+) T cells.

PMID- 18805967
TI  - Genetic associations with thalidomide mediated venous thrombotic events in
      myeloma identified using targeted genotyping.
AB  - A venous thromboembolism (VTE) with the subsequent risk of pulmonary embolism is
      a major concern in the treatment of patients with multiple myeloma with
      thalidomide. The susceptibility to developing a VTE in response to thalidomide
      therapy is likely to be influenced by both genetic and environmental factors. To
      test genetic variation associated with treatment related VTE in patient
      peripheral blood DNA, we used a custom-built molecular inversion probe (MIP)
      based single nucleotide polymorphism (SNP) chip containing 3404 SNPs. SNPs on the
      chip were selected in "functional regions" within 964 genes spanning 67 molecular
      pathways thought to be involved in the pathogenesis, treatment response, and side
      effects associated with myeloma therapy. Patients and controls were taken from 3
      large clinical trials: Medical Research Council (MRC) Myeloma IX, Hovon-50, and
      Eastern Cooperative Oncology Group (ECOG) EA100, which compared conventional
      treatments with thalidomide in patients with myeloma. Our analysis showed that
      the set of SNPs associated with thalidomide-related VTE were enriched in genes
      and pathways important in drug transport/metabolism, DNA repair, and cytokine
      balance. The effects of the SNPs associated with thalidomide-related VTE may be
      functional at the level of the tumor cell, the tumor-related microenvironment,
      and the endothelium. The clinical trials described in this paper have been
      registered as follows: MRC Myeloma IX: ISRCTN68454111; Hovon-50: NCT00028886; and
      ECOG EA100: NCT00033332.

PMID- 18805968
TI  - Role of the small GTPase Rap1 for integrin activity regulation in endothelial
      cells and angiogenesis.
AB  - Ras-associated protein 1 (Rap1), a small GTPase, attracted attention because of
      its involvement in several aspects of cell adhesion, including integrin- and
      cadherin-mediated adhesion. Yet, the role of Rap1 genes and of Rap1 effectors for
      angiogenesis has not been investigated. Human umbilical vein endothelial cells
      (HUVECs) express Rap1a and Rap1b mRNA. To determine the contribution of Rap1
      activity for angiogenesis, we overexpressed Rap1GAP1, a GTPase-activating protein
      that inhibits Rap1 activity. Overexpression of Rap1GAP1 significantly blocked
      angiogenic sprouting and tube-forming activity of HUVECs as well as migration and
      integrin-dependent adhesion. Silencing of Rap1a, Rap1b, or both significantly
      blocked HUVECs sprouting under basal and basic fibroblast growth factor
      stimulated conditions and reduced HUVEC migration and integrin-dependent
      adhesion. We found that Rap1a and Rap1b are essential for the conformational
      activation of beta(1)-integrins in endothelial cells. Furthermore, silencing of
      Rap1a and Rap1b prevented phosphorylation of tyrosine 397 in focal adhesion
      kinase (FAK) and vascular endothelial growth factor-induced Akt1-activation.
      Rap1a(-/-)-deficient and Rap1a(+/-) heterozygote mice displayed reduced
      neovascularization after hind limb ischemia compared with wild-type mice.
      Silencing of RAPL significantly blocked the Rap1-induced sprouting of HUVECs,
      suggesting that the angiogenic activity of Rap1 is partly mediated by RAPL. Our
      data demonstrate a critical role of Rap1 in the regulation of beta(1)-integrin
      affinity, adhesion, and migration in endothelial cells and in postnatal
      neovascularization.

PMID- 18805969
TI  - Interleukin-1-mediated hematopoietic cell regulation in the aorta-gonad
      mesonephros region of the mouse embryo.
AB  - Hematopoiesis during development is a dynamic process, with many factors involved
      in the emergence and regulation of hematopoietic stem cells (HSCs) and progenitor
      cells. Whereas previous studies have focused on developmental signaling and
      transcription factors in embryonic hematopoiesis, the role of well-known adult
      hematopoietic cytokines in the embryonic hematopoietic system has been largely
      unexplored. The cytokine interleukin-1 (IL-1), best known for its proinflammatory
      properties, has radioprotective effects on adult bone marrow HSCs, induces HSC
      mobilization, and increases HSC proliferation and/or differentiation. Here we
      examine IL-1 and its possible role in regulating hematopoiesis in the
      midgestation mouse embryo. We show that IL-1, IL-1 receptors (IL-1Rs), and
      signaling mediators are expressed in the aorta-gonad-mesonephros (AGM) region
      during the time when HSCs emerge in this site. IL-1 signaling is functional in
      the AGM, and the IL-1RI is expressed ventrally in the aortic subregion by some
      hematopoietic, endothelial, and mesenchymal cells. In vivo analyses of IL-1RI
      deficient embryos show an increased myeloid differentiation, concomitant with a
      slight decrease in AGM HSC activity. Our results suggest that IL-1 is an
      important homeostatic regulator at the earliest time of HSC development, acting
      to limit the differentiation of some HSCs along the myeloid lineage.

PMID- 18805970
TI  - MacAB is involved in the secretion of Escherichia coli heat-stable enterotoxin
      II.
AB  - The heat-stable enterotoxin (ST) produced by enterotoxigenic Escherichia coli is
      an extracellular peptide toxin that evokes watery diarrhea in the host. Two types
      of STs, STI and STII, have been found. Both STs are synthesized as precursor
      proteins and are then converted to the active forms with intramolecular disulfide
      bonds after being released into the periplasm. The active STs are finally
      translocated across the outer membrane through a tunnel made by TolC. However, it
      is unclear how the active STs formed in the periplasm are led to the TolC
      channel. Several transporters in the inner membrane and their periplasmic
      accessory proteins are known to combine with TolC and form a tripartite transport
      system. We therefore expect such transporters to also act as a partner with TolC
      to export STs from the periplasm to the exterior. In this study, we carried out
      pulse-chase experiments using E. coli BL21(DE3) mutants in which various
      transporter genes (acrAB, acrEF, emrAB, emrKY, mdtEF, macAB, and yojHI) had been
      knocked out and analyzed the secretion of STs in those strains. The results
      revealed that the extracellular secretion of STII was largely decreased in the
      macAB mutant and the toxin molecules were accumulated in the periplasm, although
      the secretion of STI was not affected in any mutant used in this study. The
      periplasmic stagnation of STII in the macAB mutant was restored by the
      introduction of pACYC184, containing the macAB gene, into the cell. These results
      indicate that MacAB, an ATP-binding cassette transporter of MacB and its
      accessory protein, MacA, participates in the translocation of STII from the
      periplasm to the exterior. Since it has been reported that MacAB cooperates with
      TolC, we propose that the MacAB-TolC system captures the periplasmic STII
      molecules and exports the toxin molecules to the exterior.

PMID- 18805971
TI  - Passage through Tetrahymena tropicalis triggers a rapid morphological
      differentiation in Legionella pneumophila.
AB  - The intracellular bacterial pathogen Legionella pneumophila follows a
      developmental cycle in which replicative forms (RFs) differentiate into
      infectious stationary-phase forms (SPFs) in vitro and in vivo into highly
      infectious mature intracellular forms (MIFs). The potential relationships between
      SPFs and MIFs remain uncharacterized. Previously we determined that L.
      pneumophila survives, but does not replicate, while it transiently resides (for 1
      to 2 h) in food vacuoles of the freshwater ciliate Tetrahymena tropicalis before
      being expelled as legionellae-laden pellets. We report here that SPFs have the
      ability to rapidly (<1 h) and directly (in the absence of bacterial replication)
      differentiate into MIFs while in transit through T. tropicalis, indicating that
      SPFs and MIFs constitute a differentiation continuum. Mutant RFs lacking the
      sigma factor gene rpoS, or the response regulator gene letA, were unable to
      produce normal SPFs in vitro and did not fully differentiate into MIFs in vivo,
      further supporting the existence of a common mechanism of differentiation shared
      by SPFs and MIFs. Mutants with a defective Dot/Icm system morphologically
      differentiated into MIFs while in transit through T. tropicalis. Therefore, T.
      tropicalis has allowed us to unequivocally conclude that SPFs can directly
      differentiate into MIFs and that the Dot/Icm system is not required for
      differentiation, two events that could not be experimentally addressed before.
      The Tetrahymena model can now be exploited to study the signals that trigger MIF
      development in vivo and is the only replication-independent model reported to
      date that allows the differentiation of Dot/Icm mutants into MIFs.

PMID- 18805972
TI  - Regulation of the Salmonella enterica std fimbrial operon by DNA adenine
      methylation, SeqA, and HdfR.
AB  - DNA adenine methylase (dam) mutants of Salmonella enterica serovar Typhimurium
      grown under laboratory conditions express the std fimbrial operon, which is
      tightly repressed in the wild type. Here, we show that uncontrolled production of
      Std fimbriae in S. enterica serovar Typhimurium dam mutants contributes to
      attenuation in mice, as indicated by the observation that an stdA dam strain is
      more competitive than a dam strain upon oral infection. Dam methylation appears
      to regulate std transcription, rather than std mRNA stability or turnover. A
      genetic screen for std regulators showed that the GATC-binding protein SeqA
      directly or indirectly represses std expression, while the poorly characterized
      yifA gene product serves as an std activator. YifA encodes a putative LysR-like
      protein and has been renamed HdfR, like its Escherichia coli homolog. Activation
      of std expression by HdfR is observed only in dam and seqA backgrounds. These
      data suggest that HdfR directly or indirectly activates std transcription. Since
      SeqA is unable to bind nonmethylated DNA, it is possible that std operon
      derepression in dam and seqA mutants may result from unconstrained HdfR-mediated
      activation of std transcription. Derepression of std in dam and seqA mutants of
      S. enterica occurs in only a fraction of the bacterial population, suggesting the
      occurrence of either bistable expression or phase variation.

PMID- 18805973
TI  - Mutations in conserved helix 69 of 23S rRNA of Thermus thermophilus that affect
      capreomycin resistance but not posttranscriptional modifications.
AB  - Translocation during the elongation phase of protein synthesis involves the
      relative movement of the 30S and 50S ribosomal subunits. This movement is the
      target of tuberactinomycin antibiotics. Here, we describe the isolation and
      characterization of mutants of Thermus thermophilus selected for resistance to
      the tuberactinomycin antibiotic capreomycin. Two base substitutions, A1913U and
      mU1915G, and a single base deletion, DeltamU1915, were identified in helix 69 of
      23S rRNA, a structural element that forms part of an interribosomal subunit
      bridge with the decoding center of 16S rRNA, the site of previously reported
      capreomycin resistance base substitutions. Capreomycin resistance in other
      bacteria has been shown to result from inactivation of the TlyA methyltransferase
      which 2'-O methylates C1920 of 23S rRNA. Inactivation of the tlyA gene in T.
      thermophilus does not affect its sensitivity to capreomycin. Finally, none of the
      mutations in helix 69 interferes with methylation at C1920 or with
      pseudouridylation at positions 1911 and 1917. We conclude that the resistance
      phenotype is a consequence of structural changes introduced by the mutations.

PMID- 18805974
TI  - SigF controls carotenoid pigment production and affects transformation efficiency
      and hydrogen peroxide sensitivity in Mycobacterium smegmatis.
AB  - Carotenoids are complex lipids that are known for acting against photodynamic
      injury and free radicals. We demonstrate here that sigma(F) is required for
      carotenoid pigment production in Mycobacterium smegmatis. We further show that a
      sigF mutant exhibits a transformation efficiency 10(4)-fold higher than that of
      the parental strain, suggesting that sigma(F) regulates the production of
      components affecting cell wall permeability. In addition, a sigF mutant showed an
      increased sensitivity to hydrogen peroxide. An in silico search of the M.
      smegmatis genome identified a number of SigF consensus sites, including sites
      upstream of the carotenoid synthesis locus, which explains its SigF regulation.

PMID- 18805975
TI  - YspM, a newly identified Ysa type III secreted protein of Yersinia
      enterocolitica.
AB  - Yersinia enterocolitica has three type three secretion systems, the flagellar,
      the plasmid Ysc type III secretion system (T3SS), and the chromosomal Ysa T3SS.
      The Ysc T3SS, through the proteins it secretes (Yops), prevents phagocytosis of
      Y. enterocolitica and is required for disease processes in the mouse host. Recent
      data demonstrate a role for the Ysa T3SS during initial colonization of the mouse
      via secretion of Ysps (Yersinia secreted proteins). This work characterizes the
      discovery of a newly identified Ysa type III secreted protein, YspM. Expression
      of yspM is regulated by temperature, NaCl concentration, and other known
      regulators of the ysa system. In addition, YspM is translocated into host cells
      via the Ysa T3SS. YspM is homologous to proteins classified as GDSL bacterial
      lipases, which possess a catalytic triad of amino acids (Ser, Asp, and His)
      located in three of five blocks of amino acid identity. Sequence analysis of the
      JB580v strain of Y. enterocolitica shows that, due to a premature stop codon, it
      no longer encodes the fifth block of amino acid identity containing the predicted
      catalytic histidine. However, seven other biotype 1B strains sequenced did
      possess the domain. A functional difference between the forms was revealed when
      YspM was expressed in Saccharomyces cerevisiae. Yeast growth was uninhibited when
      YspM from JB580v was expressed but greatly inhibited when YspM from Y295
      (YspM(Y295)) was expressed. Site-directed mutagenesis of the histidine of
      YspM(Y295) ablated the toxic effects. These results indicate that YspM is
      secreted by the Ysa T3SS and that, possibly due to lipase activity, it targets
      eukaryotic cellular component(s).

PMID- 18805976
TI  - Mechanism of 4-nitrophenol oxidation in Rhodococcus sp. Strain PN1:
      characterization of the two-component 4-nitrophenol hydroxylase and regulation of
      its expression.
AB  - 4-Nitrophenol (4-NP) is a toxic product of the hydrolysis of organophosphorus
      pesticides such as parathion in soil. Rhodococcus sp. strain PN1 degrades 4-NP
      via 4-nitrocatechol (4-NC) for use as the sole carbon, nitrogen, and energy
      source. A 5-kb EcoRI DNA fragment previously cloned from PN1 contained a gene
      cluster (nphRA1A2) involved in 4-NP oxidation. From sequence analysis, this gene
      cluster is expected to encode an AraC/XylS family regulatory protein (NphR) and a
      two-component 4-NP hydroxylase (NphA1 and NphA2). A transcriptional assay in a
      Rhodococcus strain revealed that the transcription of nphA1 is induced by only 4
      NP (of several phenolic compounds tested) in the presence of nphR, which is
      constitutively expressed. Disruption of nphR abolished transcriptional activity,
      suggesting that nphR encodes a positive regulatory protein. The two proteins of
      the 4-NP hydroxylase, NphA1 and NphA2, were independently expressed in
      Escherichia coli and purified by ion-exchange chromatography or affinity
      chromatography. The purified NphA2 reduced flavin adenine dinucleotide (FAD) with
      the concomitant oxidation of NADH, while the purified NphA1 oxidized 4-NP into 4
      NC almost quantitatively in the presence of FAD, NADH, and NphA2. This functional
      analysis, in addition to the sequence analysis, revealed that this enzyme system
      belongs to the two-component flavin-diffusible monooxygenase family. The 4-NP
      hydroxylase showed comparable oxidation activities for phenol and 4-chlorophenol
      to that for 4-NP and weaker activities for 3-NP and 4-NC.

PMID- 18805977
TI  - Synergistic contribution of the Legionella pneumophila lqs genes to pathogen-host
      interactions.
AB  - The causative agent of Legionnaires' disease, Legionella pneumophila, is a
      natural parasite of environmental protozoa and employs a biphasic life style to
      switch between a replicative and a transmissive (virulent) phase. L. pneumophila
      harbors the lqs (Legionella quorum sensing) cluster, which includes genes
      encoding the autoinducer synthase LqsA, the sensor kinase LqsS, the response
      regulator LqsR, and a homologue of HdeD, which is involved in acid resistance in
      Escherichia coli. LqsR promotes host-cell interactions as an element of the
      stationary-phase virulence regulatory network. Here, we characterize L.
      pneumophila mutant strains lacking all four genes of the lqs cluster or only the
      hdeD gene. While an hdeD mutant strain did not have overt physiological or
      virulence phenotypes, an lqs mutant showed an aberrant morphology in stationary
      growth phase and was defective for intracellular growth, efficient phagocytosis,
      and cytotoxicity against host cells. Cytotoxicity was restored upon
      reintroduction of the lqs genes into the chromosome of an lqs mutant strain. The
      deletion of the lqs cluster caused more-severe phenotypes than deletion of only
      lqsR, suggesting a synergistic effect of the other lqs genes. A transcriptome
      analysis indicated that in the stationary phase more than 380 genes were
      differentially regulated in the lqs mutant and wild-type L. pneumophila. Genes
      involved in protein production, metabolism, and bioenergetics were upregulated in
      the lqs mutant, whereas genes encoding virulence factors, such as effectors
      secreted by the Icm/Dot type IV secretion system, were downregulated. A proteome
      analysis revealed that a set of Icm/Dot substrates is not produced in the absence
      of the lqs gene cluster, which confirms the findings from DNA microarray assays
      and mirrors the virulence phenotype of the lqs mutant strain.

PMID- 18805978
TI  - Characterization of a Streptococcus sp.-Veillonella sp. community
      micromanipulated from dental plaque.
AB  - Streptococci and veillonellae occur in mixed-species colonies during formation of
      early dental plaque. One factor hypothesized to be important in assembly of these
      initial communities is coaggregation (cell-cell recognition by genetically
      distinct bacteria). Intrageneric coaggregation of streptococci occurs when a
      lectin-like adhesin on one streptococcal species recognizes a receptor
      polysaccharide (RPS) on the partner species. Veillonellae also coaggregate with
      streptococci. These genera interact metabolically; lactic acid produced by
      streptococci is a carbon source for veillonellae. To transpose these interactions
      from undisturbed dental plaque to an experimentally tractable in vitro biofilm
      model, a community consisting of RPS-bearing streptococci juxtaposed with
      veillonellae was targeted by quantum dot-based immunofluorescence and then
      micromanipulated off the enamel surface and cultured. Besides the expected
      antibody-reactive cell types, a non-antibody-reactive streptococcus invisible
      during micromanipulation was obtained. The streptococci were identified as
      Streptococcus oralis (RPS bearing) and Streptococcus gordonii (adhesin bearing).
      The veillonellae could not be cultivated; however, a veillonella 16S rRNA gene
      sequence was amplified from the original isolation mixture, and this sequence was
      identical to the sequence of the previously studied organism Veillonella sp.
      strain PK1910, an oral isolate in our culture collection. S. oralis coaggregated
      with S. gordonii by an RPS-dependent mechanism, and both streptococci
      coaggregated with PK1910, which was used as a surrogate during in vitro community
      reconstruction. The streptococci and strain PK1910 formed interdigitated three
      species clusters when grown as a biofilm using saliva as the nutritional source.
      PK1910 grew only when streptococci were present. This study confirms that RPS
      mediated intrageneric coaggregation occurs in the earliest stages of plaque
      formation by bringing bacteria together to create a functional community.

PMID- 18805979
TI  - Two homologous Agr-like quorum-sensing systems cooperatively control adherence,
      cell morphology, and cell viability properties in Lactobacillus plantarum WCFS1.
AB  - A two-component regulatory system of Lactobacillus plantarum, encoded by genes
      designated lamK and lamR (hpk10 and rrp10), was studied. The lamK and lamR genes
      encode proteins which are highly homologous to the quorum-sensing histidine
      kinase LamC and the response regulator LamA, respectively. Transcription analysis
      of the lamKR operon and the lamBDCA operon and liquid chromatography-mass
      spectrometry analysis of production of the LamD558 autoinducing peptide were
      performed for DeltalamA, DeltalamR, DeltalamA DeltalamR deletion mutants and a
      wild-type strain. The results suggested that lamA and lamR are cooperating genes.
      In addition, typical phenotypes of the DeltalamA mutant, such as reduced
      adherence to glass surfaces and filamentous cell morphology, were enhanced in the
      DeltalamA DeltalamR mutant. Microarray analysis suggested that the same cell wall
      polysaccharide synthesis genes, stress response-related genes, and cell wall
      protein-encoding genes were affected in the DeltalamA and DeltalamA DeltalamR
      mutants. However, the regulation ratio was more significant for the DeltalamA
      DeltalamR mutant, indicating the cooperative effect of LamA and LamR.

PMID- 18805980
TI  - Assemblies of DivIVA mark sites for hyphal branching and can establish new zones
      of cell wall growth in Streptomyces coelicolor.
AB  - Time-lapse imaging of Streptomyces hyphae revealed foci of the essential protein
      DivIVA at sites where lateral branches will emerge. Overexpression experiments
      showed that DivIVA foci can trigger establishment of new zones of cell wall
      assembly, suggesting a key role of DivIVA in directing peptidoglycan synthesis
      and cell shape in Streptomyces.

PMID- 18805981
TI  - Characterization of conserved bases in 4.5S RNA of Escherichia coli by
      construction of new F' factors.
AB  - To more clearly understand the function of conserved bases of 4.5S RNA, the
      product of the essential ffs gene of Escherichia coli, and to address conflicting
      results reported in other studies, we have developed a new genetic system to
      characterize ffs mutants. Multiple ffs alleles were generated by altering
      positions that correspond to the region of the RNA molecule that interacts
      directly with Ffh in assembly of the signal recognition particle. To facilitate
      characterization of the ffs mutations with minimal manipulation, recombineering
      was used to construct new F' factors to easily move each allele into different
      genetic backgrounds for expression in single copy. In combination with plasmids
      that expressed ffs in multiple copy numbers, the F' factors provided an accurate
      assessment of the ability of the different 4.5S RNA mutants to function in vivo.
      Consistent with structural analysis of the signal recognition particle (SRP),
      highly conserved bases in 4.5S RNA are important for binding Ffh. Despite the
      high degree of conservation, however, only a single base (C62) was indispensable
      for RNA function under all conditions tested. To quantify the interaction between
      4.5S RNA and Ffh, an assay was developed to measure the ability of mutant 4.5S
      RNA molecules to copurify with Ffh. Defects in Ffh binding correlated with loss
      of SRP-dependent protein localization. Real-time quantitative PCR was also used
      to measure the levels of wild-type and mutant 4.5S RNA expressed in vivo. These
      results clarify inconsistencies from prior studies and yielded a convenient
      method to study the function of multiple alleles.

PMID- 18805982
TI  - Modification of Pseudomonas aeruginosa Pa5196 type IV Pilins at multiple sites
      with D-Araf by a novel GT-C family Arabinosyltransferase, TfpW.
AB  - Pseudomonas aeruginosa Pa5196 produces type IV pilins modified with unusual
      alpha1,5-linked d-arabinofuranose (alpha1,5-D-Araf) glycans, identical to those
      in the lipoarabinomannan and arabinogalactan cell wall polymers from
      Mycobacterium spp. In this work, we identify a second strain of P. aeruginosa,
      PA7, capable of expressing arabinosylated pilins and use a combination of site
      directed mutagenesis, electrospray ionization mass spectrometry (MS), and
      electron transfer dissociation MS to identify the exact sites and extent of pilin
      modification in strain Pa5196. Unlike previously characterized type IV pilins
      that are glycosylated at a single position, those from strain Pa5196 were
      modified at multiple sites, with modifications of alphabeta-loop residues Thr64
      and Thr66 being important for normal pilus assembly. Trisaccharides of alpha1,5-D
      Araf were the principal modifications at Thr64 and Thr66, with additional mono-
      and disaccharides identified on Ser residues within the antiparallel beta sheet
      region of the pilin. TfpW was hypothesized to encode the pilin
      glycosyltransferase based on its genetic linkage to the pilin, weak similarity to
      membrane-bound GT-C family glycosyltransferases (which include the Mycobacterium
      arabinosyltransferases EmbA/B/C), and the presence of characteristic motifs. Loss
      of TfpW or mutation of key residues within the signature GT-C glycosyltransferase
      motif completely abrogated pilin glycosylation, confirming its involvement in
      this process. A Pa5196 pilA mutant complemented with other Pseudomonas pilins
      containing potential sites of modification expressed nonglycosylated pilins,
      showing that TfpW's pilin substrate specificity is restricted. TfpW is the
      prototype of a new type IV pilin posttranslational modification system and the
      first reported gram-negative member of the GT-C glycosyltransferase family.

PMID- 18805983
TI  - Posttranslational modification influences the effects of MgrA on norA expression
      in Staphylococcus aureus.
AB  - MgrA is a global regulator in Staphylococcus aureus. Differences in the effects
      of MgrA on norA expression have been reported for different strains, which varied
      in rsbU, a gene that affects the expression of sigB, which encodes an alternative
      sigma factor involved in stress responses. We hypothesized that MgrA was modified
      by sigB-dependent factors that affected its ability to control the expression of
      the norA efflux pump. Heterologously expressed MgrA purified from Escherichia
      coli was incubated with crude extracts (CE) from strains RN6390 (rsbU) and SH1000
      (rsbU(+)) and tested for binding to the norA promoter. Purified MgrA exhibited
      greater binding to norA promoter DNA after being incubated with SH1000 CE than
      MgrA incubated with the RN6390 CE. Phosphorylation of MgrA occurring in cell
      extracts caused it to lose the ability to bind norA promoter DNA. Overexpression
      of pknB, encoding a candidate serine/threonine kinase, produced increased phospho
      MgrA and led to a fivefold increase in the transcript level of norA for both
      RN6390 and SH1000, as well as a fourfold increase in the MICs of norfloxacin and
      ciprofloxacin for these two strains. The levels of expression of pknB in RN6390
      and SH1000, however, indicated that additional factors related to rsbU or sigB
      contribute to the differential regulatory effects of MgrA on norA expression.

PMID- 18805984
TI  - Transcriptional regulation of the citrate gene cluster of Enterococcus faecalis
      Involves the GntR family transcriptional activator CitO.
AB  - The genome of the gram-positive bacterium Enterococcus faecalis contains the
      genes that encode the citrate lyase complex. This complex splits citrate into
      oxaloacetate and acetate and is involved in all the known anaerobic bacterial
      citrate fermentation pathways. Although citrate fermentation in E. faecalis has
      been investigated before, the regulation and transcriptional pattern of the cit
      locus has still not been fully explored. To fill this gap, in this paper we
      demonstrate that the GntR transcriptional regulator CitO is a novel positive
      regulator involved in the expression of the cit operons. The transcriptional
      analysis of the cit clusters revealed two divergent operons: citHO, which codes
      for the transporter (citH) and the regulatory protein (citO), and upstream from
      it and in the opposite direction the oadHDB-citCDEFX-oadA-citMG operon, which
      includes the citrate lyase subunits (citD, citE, and citF), the soluble
      oxaloacetate decarboxylase (citM), and also the genes encoding a putative
      oxaloacetate decarboxylase complex (oadB, oadA, oadD and oadH). This analysis
      also showed that both operons are specifically activated by the addition of
      citrate to the medium. In order to study the functional role of CitO, a mutant
      strain with an interrupted citO gene was constructed, causing a total loss of the
      ability to degrade citrate. Reintroduction of a functional copy of citO to the
      citO-deficient strain restored the response to citrate and the Cit(+) phenotype.
      Furthermore, we present evidence that CitO binds to the cis-acting sequences O(1)
      and O(2), located in the cit intergenic region, increasing its affinity for these
      binding sites when citrate is present and allowing the induction of both cit
      promoters.

PMID- 18805985
TI  - SciN is an outer membrane lipoprotein required for type VI secretion in
      enteroaggregative Escherichia coli.
AB  - Enteroaggregative Escherichia coli (EAEC) is a pathogen implicated in several
      infant diarrhea or diarrheal outbreaks in areas of endemicity. Although multiple
      genes involved in EAEC pathogenesis have been identified, the overall mechanism
      of virulence is not well understood. Recently, a novel secretion system, called
      type VI secretion (T6S) system (T6SS), has been identified in EAEC and most
      animal or plant gram-negative pathogens. T6SSs are multicomponent cell envelope
      machines responsible for the secretion of at least two putative substrates, Hcp
      and VgrG. In EAEC, two copies of T6S gene clusters, called sci-1 and sci-2, are
      present on the pheU pathogenicity island. In this study, we focused our work on
      the sci-1 gene cluster. The Sci-1 apparatus is probably composed of all, or a
      subset of, the 21 gene products encoded on the cluster. Among these subunits,
      some are shared by all T6SSs identified to date, including a ClpV-type AAA(+)
      ATPase (SciG) and an IcmF (SciS) and an IcmH (SciP) homologue, as well as a
      putative lipoprotein (SciN). In this study, we demonstrate that sciN is a
      critical gene necessary for T6S-dependent secretion of the Hcp-like SciD protein
      and for biofilm formation. We further show that SciN is a lipoprotein, as shown
      by the inhibition of its processing by globomycin and in vivo labeling with
      [(3)H]palmitic acid. SciN is tethered to the outer membrane and exposed in the
      periplasm. Sequestration of SciN at the inner membrane by targeting the +2
      residue responsible for lipoprotein localization (Gly2Asp) fails to complement an
      sciN mutant for SciD secretion and biofilm formation. Together, these results
      support a model in which SciN is an outer membrane lipoprotein exposed in the
      periplasm and essential for the Sci-1 apparatus function.

PMID- 18805986
TI  - Kinetic analysis of growth rate, ATP, and pigmentation suggests an energy
      spilling function for the pigment prodigiosin of Serratia marcescens.
AB  - Serratia marcescens is a gram-negative environmental bacterium and opportunistic
      pathogen. S. marcescens expresses prodigiosin, a bright red and cell-associated
      pigment which has no known biological function for producing cells. We present
      here a kinetic model relating cell, ATP, and prodigiosin concentration changes
      for S. marcescens during cultivation in batch culture. Cells were grown in a
      variety of complex broth media at temperatures which either promoted or
      essentially prevented pigmentation. High growth rates were accompanied by large
      decreases in cellular prodigiosin concentration; low growth rates were associated
      with rapid pigmentation. Prodigiosin was induced most strongly during limited
      growth as the population transitioned to stationary phase, suggesting a negative
      effect of this pigment on biomass production. Mathematically, the combined rate
      of formation of biomass and bioenergy (as ATP) was shown to be equivalent to the
      rate of prodigiosin production. Studies with cyanide inhibition of both oxidative
      phosphorylation and pigment production indicated that rates of biomass and net
      ATP synthesis were actually higher in the presence of cyanide, further suggesting
      a negative regulatory role for prodigiosin in cell and energy production under
      aerobic growth conditions. Considered in the context of the literature, these
      results suggest that prodigiosin reduces ATP production by a process termed
      energy spilling. This process may protect the cell by limiting production of
      reactive oxygen compounds. Other possible functions for prodigiosin as a mediator
      of cell death at population stationary phase are discussed.

PMID- 18805987
TI  - Alr0397 is an outer membrane transporter for the siderophore schizokinen in
      Anabaena sp. strain PCC 7120.
AB  - Iron uptake in proteobacteria by TonB-dependent outer membrane transporters
      represents a well-explored subject. In contrast, the same process has been
      scarcely investigated in cyanobacteria. The heterocyst-forming cyanobacterium
      Anabaena sp. strain PCC 7120 is known to secrete the siderophore schizokinen, but
      its transport system has remained unidentified. Inspection of the genome of
      strain PCC 7120 shows that only one gene encoding a putative TonB-dependent iron
      transporter, namely alr0397, is positioned close to genes encoding enzymes
      involved in the biosynthesis of a hydroxamate siderophore. The expression of
      alr0397, which encodes an outer membrane protein, was elevated under iron-limited
      conditions. Inactivation of this gene caused a moderate phenotype of iron
      starvation in the mutant cells. The characterization of the mutant strain showed
      that Alr0397 is a TonB-dependent schizokinen transporter (SchT) of the outer
      membrane and that alr0397 expression and schizokinen production are regulated by
      the iron homeostasis of the cell.

PMID- 18805988
TI  - Role of two NtcA-binding sites in the complex ntcA gene promoter of the
      heterocyst-forming cyanobacterium Anabaena sp. strain PCC 7120.
AB  - Anabaena sp. strain PCC 7120 is a filamentous cyanobacterium that fixes N(2) in
      specialized cells called heterocysts, which differentiate from vegetative cells
      in a process that requires the nitrogen control transcription factor NtcA. 2
      Oxoglutarate-stimulated binding of purified NtcA to wild-type and modified
      versions of the ntcA gene promoter from Anabaena sp. was analyzed by mobility
      shift and DNase I footprinting assays, and the role of NtcA-binding sites in the
      expression of the ntcA gene during heterocyst differentiation was studied in vivo
      by using an ntcA-gfp translational fusion and primer extension analysis. Mutation
      of neither of the two identified NtcA-binding sites eliminated localized
      expression of ntcA in proheterocysts, but mutation of both sites led to very low,
      nonlocalized expression.

PMID- 18805989
TI  - TAp73 knockout shows genomic instability with infertility and tumor suppressor
      functions.
AB  - The Trp53 gene family member Trp73 encodes two major groups of protein isoforms,
      TAp73 and DeltaNp73, with opposing pro- and anti-apoptotic functions;
      consequently, their relative ratio regulates cell fate. However, the precise
      roles of p73 isoforms in cellular events such as tumor initiation, embryonic
      development, and cell death remain unclear. To determine which aspects of p73
      function are attributable to the TAp73 isoforms, we generated and characterized
      mice in which exons encoding the TAp73 isoforms were specifically deleted to
      create a TAp73-deficient (TAp73(-/-)) mouse. Here we show that mice specifically
      lacking in TAp73 isoforms develop a phenotype intermediate between the phenotypes
      of Trp73(-/-) and Trp53(-/-) mice with respect to incidence of spontaneous and
      carcinogen-induced tumors, infertility, and aging, as well as hippocampal
      dysgenesis. In addition, cells from TAp73(-/-) mice exhibit genomic instability
      associated with enhanced aneuploidy, which may account for the increased
      incidence of spontaneous tumors observed in these mutants. Hence, TAp73 isoforms
      exert tumor-suppressive functions and indicate an emerging role for Trp73 in the
      maintenance of genomic stability.

PMID- 18805990
TI  - Genomic predictors of interindividual differences in response to DNA damaging
      agents.
AB  - Human lymphoblastoid cells derived from different healthy individuals display
      considerable variation in their transcription profiles. Here we show that such
      variation in gene expression underlies interindividual susceptibility to DNA
      damaging agents. The results demonstrate the massive differences in sensitivity
      across a diverse cell line panel exposed to an alkylating agent. Computational
      models identified 48 genes with basal expression that predicts susceptibility
      with 94% accuracy. Modulating transcript levels for two member genes, MYH and
      C21ORF56, confirmed that their expression does indeed influence alkylation
      sensitivity. Many proteins encoded by these genes are interconnected in cellular
      networks related to human cancer and tumorigenesis.

PMID- 18805991
TI  - Genetic analysis reveals that C19-GA 2-oxidation is a major gibberellin
      inactivation pathway in Arabidopsis.
AB  - Bioactive hormone concentrations are regulated both at the level of hormone
      synthesis and through controlled inactivation. Based on the ubiquitous presence
      of 2beta-hydroxylated gibberellins (GAs), a major inactivating pathway for the
      plant hormone GA seems to be via GA 2-oxidation. In this study, we used various
      approaches to determine the role of C(19)-GA 2-oxidation in regulating GA
      concentration and GA-responsive plant growth and development. We show that
      Arabidopsis thaliana has five C(19)-GA 2-oxidases, transcripts for one or more of
      which are present in all organs and at all stages of development examined.
      Expression of four of the five genes is subject to feed-forward regulation. By
      knocking out all five Arabidopsis C(19)-GA 2-oxidases, we show that C(19)-GA 2
      oxidation limits bioactive GA content and regulates plant development at various
      stages during the plant life cycle: C(19)-GA 2-oxidases prevent seed germination
      in the absence of light and cold stimuli, delay the vegetative and floral phase
      transitions, limit the number of flowers produced per inflorescence, and suppress
      elongation of the pistil prior to fertilization. Under GA-limited conditions,
      further roles are revealed, such as limiting elongation of the main stem and side
      shoots. We conclude that C(19)-GA 2-oxidation is a major GA inactivation pathway
      regulating development in Arabidopsis.

PMID- 18805992
TI  - A protracted and dynamic maturation schedule underlies Arabidopsis leaf
      development.
AB  - Leaf development has been monitored chiefly by following anatomical markers.
      Analysis of transcriptome dynamics during leaf maturation revealed multiple
      expression patterns that rise or fall with age or that display age-specific
      peaks. These were used to formulate a digital differentiation index (DDI) based
      on a set of selected markers with informative expression during leaf ontogeny.
      The leaf-based DDI reliably predicted the developmental state of leaf samples
      from diverse sources and was independent of mitotic cell division transcripts or
      propensity of specific cell types. When calibrated by informative root markers,
      the same algorithm accurately diagnosed dissected root samples. We used the DDI
      to characterize plants with reduced activities of multiple CINCINNATA (CIN)-TCP
      (TEOSINTE BRANCHED1, CYCLOIDEA, PCF) growth regulators. These plants had giant
      curled leaves made up of small cells with abnormal shape, low DDI scores, and low
      expression of mitosis markers, depicting the primary role of CIN-TCPs as
      promoters of differentiation. Delayed activity of several CIN-TCPs resulted in
      abnormally large but flat leaves with regular cells. The application of DDI has
      therefore portrayed the CIN-TCPs as heterochronic regulators that permit the
      development of a flexible and robust leaf form through an ordered and protracted
      maturation schedule.

PMID- 18805993
TI  - Regulation of CCN2/CTGF and related cytokines in cultured peritoneal cells under
      conditions simulating peritoneal dialysis.
AB  - BACKGROUND: Continuous ambulatory peritoneal dialysis (CAPD) is a major treatment
      modality for end-stage renal failure. The peritoneal membrane exhibits
      pathological changes that correlate with the duration of dialysis. These changes
      are due to the exposure of the peritoneum to non-physiologic peritoneal dialysis
      solution (PDS) with a high glucose content, and containing potentially toxic
      substances including glucose degradation products (GDP) and advanced glycation
      end products (AGE). Connective tissue growth factor (CTGF/CCN2) is one of the
      determinants of progressive fibrosis and peritoneal membrane dysfunction in CAPD.
      In this study, we examined the CCN2 expression and its regulation in peritoneal
      resident cells using a cell culture model. METHODS: The expression of
      transforming growth factor-beta (TGF-beta), CCN2 and vascular endothelial growth
      factor (VEGF) in human peritoneal mesothelial cells (HPMC), human peritoneal
      fibroblasts (HPF) or endothelial cell line EA.hy926 (EC) cultured with various
      PDS and their components was examined by quantitative PCR (qPCR). The modulation
      of CCN2 synthesis under the crosstalk between HPMC and HPF or EC was examined
      using a conditioned medium transfer system in which HPMC was exposed to
      conditioned media obtained from HPF or EC incubated with PDS and their
      components. The differential effects of TGF-beta, CCN2 and VEGF in inducing the
      expression of transcriptional factors as well as interleukin-6 (IL-6), matrix
      metallopeptidase 9 (MMP-9) and collagen I were examined by electrophoretic
      mobility-shift assay (EMSA) and qPCR. RESULTS: PDS and their components
      differentially modulated the expression of TGF-beta, CCN2 and VEGF in HPMC, HPF
      and EC. The expression of CCN2 by HPMC was significantly increased after cultured
      with a HPF-conditioned medium and an EC-conditioned medium. Neutralizing anti-TGF
      beta antibodies reduced but not completely abolished the CCN2 synthesis in HPMC
      cultured with the HPF- or EC-conditioned medium. CCN2, TGF-beta and VEGF
      activated distinct transcriptional factors in HPMC, which resulted in divergent
      biological responses in terms of IL-6, MMP-9 and collagen I mRNA expression.
      CONCLUSION: AGE and GDPs in PDS differentially regulate the synthesis of CCN2 by
      peritoneal resident cells. The CCN2 synthesis by HPMC can be further amplified by
      TGF-beta released from HPF or EC. The differential activation of different
      transcriptional factors and diverse response of HPMC towards CCN2, TGF-beta and
      VEGF suggest that these cytokines/growth factors have an overlapping and distinct
      role on HPMC.

PMID- 18805994
TI  - Estimating single-cell lag times via a Bayesian scheme.
AB  - Network models offer computationally efficient tools for estimating the
      variability of single-cell lag phases. Currently, optical methods for estimating
      the variability of single-cell lag phases use single-cell inocula and are
      technically challenging. A Bayesian network model incorporating small uncertain
      inocula addresses these limitations.

PMID- 18805995
TI  - Heterotrophic and autotrophic microbial populations in cold perennial springs of
      the high arctic.
AB  - The saline springs of Gypsum Hill in the Canadian high Arctic are a rare example
      of cold springs originating from deep groundwater and rising to the surface
      through thick permafrost. The heterotrophic bacteria and autotrophic sulfur
      oxidizing bacteria (up to 40% of the total microbial community) isolated from the
      spring waters and sediments were classified into four phyla (Actinobacteria,
      Bacteroidetes, Firmicutes, and Proteobacteria) based on 16S rRNA gene analysis;
      heterotrophic isolates were primarily psychrotolerant, salt-tolerant, facultative
      anaerobes. Some of the isolates contained genes for thiosulfate oxidation (soxB)
      and anoxygenic photosynthesis (pufM), possibly enabling the strains to better
      compete in these sulfur-rich environments subject to long periods of illumination
      in the Arctic summer. Although leucine uptake by the spring water microbial
      community was low, CO(2) uptake was relatively high under dark incubation,
      reinforcing the idea that primary production by chemoautotrophs is an important
      process in the springs. The small amounts of hydrocarbons in gases exsolving from
      the springs (0.38 to 0.51% CH(4)) were compositionally and isotopically
      consistent with microbial methanogenesis and possible methanotrophy. Anaerobic
      heterotrophic sulfur oxidation and aerobic autotrophic sulfur oxidation
      activities were demonstrated in sediment slurries. Overall, our results describe
      an active microbial community capable of sustainability in an extreme environment
      that experiences prolonged periods of continuous light or darkness, low
      temperatures, and moderate salinity, where life seems to rely on
      chemolithoautotrophy.

PMID- 18805996
TI  - Exogenous or L-rhamnose-derived 1,2-propanediol is metabolized via a pduD
      dependent pathway in Listeria innocua.
AB  - 1,2-Propanediol (1,2-PD) added exogenously to cultures or produced endogenously
      from l-rhamnose is metabolized to n-propanol and propionate in Listeria innocua
      Lin11. The pduD gene, which encodes a diol dehydratase ss subunit homolog, is
      required for 1,2-PD catabolism. pduD and 16 other genes within the pduA-to-pduF
      region of a large gene cluster are induced in medium containing 1,2-PD.

PMID- 18805997
TI  - Frequent occurrence of human-associated microsporidia in fecal droppings of urban
      pigeons in amsterdam, the Netherlands.
AB  - Human-associated microsporidia were frequently observed in fecal samples of 331
      feral pigeons in Amsterdam, The Netherlands, obtained during high- and low
      breeding periods. Thirty-six of 331 samples (11%) contained the human pathogens
      Enterocytozoon bieneusi (n = 18), Encephalitozoon hellem (n = 11),
      Encephalitozoon cuniculi (n = 6), and Encephalitozoon intestinalis (n = 1); 5
      samples contained other microsporidia. Pigeon feces can be an important source of
      human microsporidian infection.

PMID- 18805998
TI  - Effective mutagenesis of Vibrio fischeri by using hyperactive mini-Tn5
      derivatives.
AB  - We have developed a transposon mutagenesis system for Vibrio fischeri ES114 that
      utilizes a hyperactive mutant Tn5 transposase (E54K and M56A) and optimized
      transposon ends. Using a conjugation-based procedure, we obtained independent
      single-insertion mini-Tn5 mutants at a rate of approximately 10(-6). This simple
      and inexpensive technique represents a significant improvement over previous
      methods for transposon mutagenesis of V. fischeri and should be applicable to
      many other bacteria.

PMID- 18805999
TI  - Identification of Campylobacter jejuni proteins recognized by maternal antibodies
      of chickens.
AB  - Campylobacter jejuni is one of the leading bacterial causes of food-borne
      gastroenteritis. Infection with C. jejuni is frequently acquired through the
      consumption of undercooked poultry or foods cross-contaminated with raw poultry.
      Given the importance of poultry as a reservoir for Campylobacter organisms,
      investigators have performed studies to understand the protective role of
      maternal antibodies in the ecology of Campylobacter colonization of poultry. In a
      previous study, chicks with maternal antibodies generated against the S3B strain
      of C. jejuni provided protection against Campylobacter colonization (O. Sahin, N.
      Luo, S. Huang, and Q. Zhang, Appl. Environ. Microbiol. 69:5372-5379, 2003). We
      obtained serum samples, collectively referred to as the C. jejuni S3B-SPF sera,
      from the previous study. These sera were determined to contain maternal
      antibodies that reacted against C. jejuni whole-cell lysates as judged by enzyme
      linked immunosorbent assay. The antigens recognized by the C. jejuni S3B-SPF
      antibodies were identified by immunoblot analysis, coupled with mass
      spectrometry, of C. jejuni outer membrane protein extracts. This approach led to
      the identification of C. jejuni proteins recognized by the maternal antibodies,
      including the flagellin proteins and CadF adhesin. In vitro assays revealed that
      the C. jejuni S3B-SPF sera retarded the motility of the C. jejuni S3B homologous
      strain but did not retard the motility of a heterologous strain of C. jejuni (81
      176). This finding provides a possible mechanism explaining why maternal
      antibodies confer enhanced protection against challenge with a homologous strain
      compared to a heterologous strain. Collectively, this study provides a list of C.
      jejuni proteins against which protective antibodies are generated in hens and
      passed to chicks.

PMID- 18806000
TI  - Emergence of novel Streptococcus iniae exopolysaccharide-producing strains
      following vaccination with nonproducing strains.
AB  - Streptococcus iniae is a major pathogen of fish, producing fatal disease among
      fish species living in very diverse environments. Recently, reoccurrences of
      disease outbreaks were recorded in rainbow trout (Oncorhynchus mykiss, Walbaum)
      farms where the entire fish population was routinely vaccinated. New strains are
      distinguished from previous strains by their ability to produce large amounts of
      extracellular polysaccharide that is released into the medium. Present findings
      indicate that the extracellular polysaccharide is a major antigenic factor,
      suggesting an evolutionary selection of strains capable of extracellular
      polysaccharide production.

PMID- 18806001
TI  - Flavobacterium sp. strain 4221 and Pedobacter sp. strain 4236 beta-1,3-glucanases
      that are active at low temperatures.
AB  - Secretion of beta-1,3-glucanases by the arctic bacterial isolates 4221 and 4236,
      related to the genera Flavobacterium and Pedobacter, was discovered. Escherichia
      coli and Lactococcus lactis expression of beta-1,3-glucanases Glc4221-1 and
      Glc4236-1 from the respective isolates was achieved. The enzymes hydrolyzed
      fungal cell walls and retained activity at low temperatures.

PMID- 18806002
TI  - Temporal assessment of the impact of exposure to cow feces in two watersheds by
      multiple host-specific PCR assays.
AB  - Exposure to feces in two watersheds with different management histories was
      assessed by tracking cattle feces bacterial populations using multiple host
      specific PCR assays. In addition, environmental factors affecting the occurrence
      of these markers were identified. Each assay was performed using DNA extracts
      from water and sediment samples collected from a watershed directly impacted by
      cattle fecal pollution (WS1) and from a watershed impacted only through runoff
      (WS2). In WS1, the ruminant-specific Bacteroidales 16S rRNA gene marker CF128F
      was detected in 65% of the water samples, while the non-16S rRNA gene markers
      Bac1, Bac2, and Bac5 were found in 32 to 37% of the water samples. In contrast,
      all source-specific markers were detected in less than 6% of the water samples
      from WS2. Binary logistic regressions (BLRs) revealed that the occurrence of
      Bac32F and CF128F was significantly correlated with season as a temporal factor
      and watershed as a site factor. BLRs also indicated that the dynamics of fecal
      source-tracking markers correlated with the density of a traditional fecal
      indicator (P < 0.001). Overall, our results suggest that a combination of 16S
      rRNA gene and non-16S rRNA gene markers provides a higher level of confidence for
      tracking unknown sources of fecal pollution in environmental samples. This study
      also provided practical insights for implementation of microbial source-tracking
      practices to determine sources of fecal pollution and the influence of
      environmental variables on the occurrence of source-specific markers.

PMID- 18806003
TI  - Global transcription and metabolic flux analysis of Escherichia coli in glucose
      limited fed-batch cultivations.
AB  - A time series of whole-genome transcription profiling of Escherichia coli K-12
      W3110 was performed during a carbon-limited fed-batch process. The application of
      a constant feed rate led to the identification of a dynamic sequence of diverse
      carbon limitation responses (e.g., the hunger response) and at the same time
      provided a global view of how cellular and extracellular resources are used: the
      synthesis of high-affinity transporters guarantees maximal glucose influx,
      thereby preserving the phosphoenolpyruvate pool, and energy-dependent chemotaxis
      is reduced in order to provide a more economic "work mode." sigma(S)-mediated
      stress and starvation responses were both found to be of only minor relevance.
      Thus, the experimental setup provided access to the hunger response and enabled
      the differentiation of the hunger response from the general starvation response.
      Our previous topological model of the global regulation of the E. coli central
      carbon metabolism through the crp, cra, and relA/spoT modulons is supported by
      correlating transcript levels and metabolic fluxes and can now be extended. The
      substrate is extensively oxidized in the tricarboxylic acid (TCA) cycle to
      enhance energy generation. However, the general rate of oxidative decarboxylation
      within the pentose phosphate pathway and the TCA cycle is restricted to a
      minimum. Fine regulation of the carbon flux through these pathways supplies
      sufficient precursors for biosyntheses. The pools of at least three precursors
      are probably regulated through activation of the (phosphoenolpyruvate-)glyoxylate
      shunt. The present work shows that detailed understanding of the genetic
      regulation of bacterial metabolism provides useful insights for manipulating the
      carbon flux in technical production processes.

PMID- 18806004
TI  - Gene expression profiling of Listeria monocytogenes strain F2365 during growth in
      ultrahigh-temperature-processed skim milk.
AB  - To study how Listeria monocytogenes survives and grows in ultrahigh-temperature
      processed (UHT) skim milk, microarray technology was used to monitor the gene
      expression profiles of strain F2365 in UHT skim milk. Total RNA was isolated from
      strain F2365 in UHT skim milk after 24 h of growth at 4 degrees C, labeled with
      fluorescent dyes, and hybridized to "custom-made" commercial oligonucleotide (35
      mers) microarray chips containing the whole genome of L. monocytogenes strain
      F2365. Compared to L. monocytogenes grown in brain heart infusion (BHI) broth for
      24 h at 4 degrees C, 26 genes were upregulated (more-than-twofold increase) in
      UHT skim milk, whereas 14 genes were downregulated (less-than-twofold decrease).
      The upregulated genes included genes encoding transport and binding proteins,
      transcriptional regulators, proteins in amino acid biosynthesis and energy
      metabolism, protein synthesis, cell division, and hypothetical proteins. The
      downregulated genes included genes that encode transport and binding proteins,
      protein synthesis, cellular processes, cell envelope, energy metabolism, a
      transcriptional regulator, and an unknown protein. The gene expression changes
      determined by microarray assays were confirmed by real-time reverse transcriptase
      PCR analyses. Furthermore, cells grown in UHT skim milk displayed the same
      sensitivity to hydrogen peroxide as cells grown in BHI, demonstrating that the
      elevated levels of expression of genes encoding manganese transporter complexes
      in UHT skim milk did not result in changes in the oxidative stress sensitivity.
      To our knowledge, this report represents a novel study of global transcriptional
      gene expression profiling of L. monocytogenes in a liquid food.

PMID- 18806005
TI  - High glycolytic flux improves pyruvate production by a metabolically engineered
      Escherichia coli strain.
AB  - We report pyruvate formation in Escherichia coli strain ALS929 containing
      mutations in the aceEF, pfl, poxB, pps, and ldhA genes which encode,
      respectively, the pyruvate dehydrogenase complex, pyruvate formate lyase,
      pyruvate oxidase, phosphoenolpyruvate synthase, and lactate dehydrogenase. The
      glycolytic rate and pyruvate productivity were compared using glucose-, acetate-,
      nitrogen-, or phosphorus-limited chemostats at a growth rate of 0.15 h(-1). Of
      these four nutrient limitation conditions, growth under acetate limitation
      resulted in the highest glycolytic flux (1.60 g/g . h), pyruvate formation rate
      (1.11 g/g h), and pyruvate yield (0.70 g/g). Additional mutations in atpFH and
      arcA (strain ALS1059) further elevated the steady-state glycolytic flux to 2.38
      g/g h in an acetate-limited chemostat, with heterologous NADH oxidase expression
      causing only modest additional improvement. A fed-batch process with strain
      ALS1059 using defined medium with 5 mM betaine as osmoprotectant and an
      exponential feeding rate of 0.15 h(-1) achieved 90 g/liter pyruvate, with an
      overall productivity of 2.1 g/liter h and yield of 0.68 g/g.

PMID- 18806006
TI  - Identification of components of the sigma B regulon in Listeria monocytogenes
      that contribute to acid and salt tolerance.
AB  - Sigma B (sigma(B)) is an alternative sigma factor that controls the
      transcriptional response to stress in Listeria monocytogenes and is also known to
      play a role in the virulence of this human pathogen. In the present study we
      investigated the impact of a sigB deletion on the proteome of L. monocytogenes
      grown in a chemically defined medium both in the presence and in the absence of
      osmotic stress (0.5 M NaCl). Two new phenotypes associated with the sigB deletion
      were identified using this medium. (i) Unexpectedly, the strain with the
      DeltasigB deletion was found to grow faster than the parent strain in the growth
      medium, but only when 0.5 M NaCl was present. This phenomenon was independent of
      the carbon source provided in the medium. (ii) The DeltasigB mutant was found to
      have unusual Gram staining properties compared to the parent, suggesting that
      sigma(B) contributes to the maintenance of an intact cell wall. A proteomic
      analysis was performed by two-dimensional gel electrophoresis, using cells
      growing in the exponential and stationary phases. Overall, 11 proteins were found
      to be differentially expressed in the wild type and the DeltasigB mutant; 10 of
      these proteins were expressed at lower levels in the mutant, and 1 was
      overexpressed in the mutant. All 11 proteins were identified by tandem mass
      spectrometry, and putative functions were assigned based on homology to proteins
      from other bacteria. Five proteins had putative functions related to carbon
      utilization (Lmo0539, Lmo0783, Lmo0913, Lmo1830, and Lmo2696), while three
      proteins were similar to proteins whose functions are unknown but that are known
      to be stress inducible (Lmo0796, Lmo2391, and Lmo2748). To gain further insight
      into the role of sigma(B) in L. monocytogenes, we deleted the genes encoding four
      of the proteins, lmo0796, lmo0913, lmo2391, and lmo2748. Phenotypic
      characterization of the mutants revealed that Lmo2748 plays a role in
      osmotolerance, while Lmo0796, Lmo0913, and Lmo2391 were all implicated in acid
      stress tolerance to various degrees. Invasion assays performed with Caco-2 cells
      indicated that none of the four genes was required for mammalian cell invasion.
      Microscopic analysis suggested that loss of Lmo2748 might contribute to the cell
      wall defect observed in the DeltasigB mutant. Overall, this study highlighted two
      new phenotypes associated with the loss of sigma(B). It also demonstrated clear
      roles for sigma(B) in both osmotic and low-pH stress tolerance and identified
      specific components of the sigma(B) regulon that contribute to the responses
      observed.

PMID- 18806007
TI  - Early use of memantine for neuropathic pain.

PMID- 18806008
TI  - Whodunnit: the mysterious case of mediastinitis after continuous interscalene
      block.

PMID- 18806009
TI  - Faculty teaching scores: validating evaluations, evaluating validation.

PMID- 18806010
TI  - Anesthesia information management systems: almost there.

PMID- 18806011
TI  - Perioperative blood pressure management: does central vascular stiffness matter?

PMID- 18806012
TI  - The ECLIPSE trials: comparative studies of clevidipine to nitroglycerin, sodium
      nitroprusside, and nicardipine for acute hypertension treatment in cardiac
      surgery patients.
AB  - BACKGROUND: Acute hypertension during cardiac surgery can be difficult to manage
      and may adversely affect patient outcomes. Clevidipine is a novel, rapidly acting
      dihydropyridine L-type calcium channel blocker with an ultrashort half-life that
      decreases arterial blood pressure (BP). The Evaluation of CLevidipine In the
      Perioperative Treatment of Hypertension Assessing Safety Events trial (ECLIPSE)
      was performed to compare the safety and efficacy of clevidipine (CLV) with
      nitroglycerin (NTG), sodium nitroprusside (SNP), and nicardipine (NIC) in the
      treatment of perioperative acute hypertension in patients undergoing cardiac
      surgery. METHODS: We analyzed data from three prospective, randomized, open
      label, parallel comparison studies of CLV to NTG or SNP perioperatively, or NIC
      postoperatively in patients undergoing cardiac surgery at 61 medical centers. Of
      the 1964 patients enrolled, 1512 met postrandomization inclusion criteria of
      requiring acute treatment of hypertension based on clinical criteria. The
      patients were randomized 1:1 for each of the three parallel comparator treatment
      groups. The primary outcome was the incidence of death, myocardial infarction,
      stroke or renal dysfunction at 30 days. Adequacy and precision of BP control was
      evaluated and is reported as a secondary outcome. RESULTS: There was no
      difference in the incidence of myocardial infarction, stroke or renal dysfunction
      for CLV-treated patients compared with the other treatment groups. There was no
      difference in mortality rates between the CLV, NTG or NIC groups. Mortality was
      significantly higher, though, for SNP-treated patients compared with CLV-treated
      patients (P=0.04). CLV was more effective compared with NTG (P=0.0006) or SNP
      (P=0.003) in maintaining BP within the prespecified BP range. CLV was equivalent
      to NIC in keeping patients within a prespecified BP range; however, when BP range
      was narrowed, CLV was associated with fewer BP excursions beyond these BP limits
      compared with NIC. CONCLUSIONS: CLV is a safe and effective treatment for acute
      hypertension in patients undergoing cardiac surgery.

PMID- 18806014
TI  - Preservation of the positive lusitropic effect of beta-adrenoceptors stimulation
      in diabetic cardiomyopathy.
AB  - BACKGROUND: In diabetic cardiomyopathy, diastolic dysfunction results in part
      from sarcoplasmic reticulum abnormalities affecting both phospholamban and
      sarcoplasmic reticulum Ca2+ uptake (SERCA2a). Consequently, the positive
      lusitropic effect of beta-adrenoceptors stimulation could be altered, and beta3
      adrenoceptor over-expression may play a role, as previously demonstrated with an
      altered positive inotropic effect. In this study, we tested the hypothesis that
      the beta-adrenergic positive lusitropic effect is altered in diabetic
      cardiomyopathy, and that beta3-adrenoceptor over-expression is involved. METHODS:
      beta-adrenergic responses were investigated in vivo (dobutamine-echocardiography)
      and in vitro (papillary muscle preparation) in healthy and diabetic rats killed 4
      (4W) and 12 (12W) wk after IV streptozotocin injection. The effect of beta3
      adrenoceptor pathway inhibition by S-cyanopindolol (selective beta3-adrenoceptor
      antagonist) or by NG-nitro-L-arginine-methyl-ester (nonselective nitric oxide
      synthase inhibitor) on the lusitropic response to isoproterenol (nonselective
      beta-adrenoceptors agonist) was studied in vitro. Western blots were performed to
      quantify the protein expressions of beta1- and beta3-adrenoceptors,
      phospholamban, and SERCA2a. Data are presented as mean percentages of baseline+/
      sd. RESULTS: Despite the increased phospholamban/SERCA2a protein ratio and
      documented diastolic dysfunction, the positive lusitropic effect of beta
      adrenoceptors stimulation was preserved in vivo (dobutamine) and in vitro
      (isoproterenol) in 4W and 12W diabetic, compared with healthy, rats. The beta3
      adrenoceptor was up-regulated whereas beta1-adrenoceptor was down-regulated in 4W
      and 12W diabetic, compared with healthy, rats. Nevertheless, S-cyanopindolol or
      NG-nitro-L-arginine-methyl-ester had no lusitropic effect. CONCLUSIONS: The
      positive lusitropic effect of beta-adrenoceptor stimulation was preserved in
      diabetic cardiomyopathy. beta3-adrenoceptor over-expression does not seem to
      affect this process.

PMID- 18806013
TI  - Pulse pressure and risk of adverse outcome in coronary bypass surgery.
AB  - BACKGROUND: Among ambulatory patients, an increase in pulse pressure (PP) is a
      well-established determinant of vascular risk. The relationship of PP and acute
      perioperative vascular outcome among patients having coronary artery bypass graft
      (CABG) surgery is less well known. METHODS: We conducted a prospective
      observational study involving 5436 patients having elective CABG surgery
      requiring cardiopulmonary bypass. Of these, 4801 met final inclusion criteria.
      Comprehensive data were captured for medical history, intraoperative and
      postoperative physiologic and laboratory measures, diagnostic testing, and
      clinical events. The relationship between preoperative hypertension (systolic,
      diastolic, PP) and ischemic cardiac and cerebral outcomes and death was assessed
      using multivariable logistic regression; P<0.05 was considered significant.
      RESULTS: Nine hundred and seventeen patients (19.1%) had fatal and nonfatal
      vascular complications, including 146 patients (3.0%) with cerebral and 715
      patients (14.9%) with cardiac events. In-hospital mortality occurred in 147
      patients (3.1%). Among all blood pressure variables measured preoperatively, PP
      was most strongly associated with an increased risk of postoperative
      complications. PP increments of 10 mm Hg (above a threshold of 40 mm Hg) were
      associated with an increased risk of cerebral events (adjusted odds ratio: 1.12;
      95% CI [1.002-1.28]; P=0.026). The incidence of a cerebral event and/or death
      from neurologic complications nearly doubled for patients with PP>80 mm Hg
      versus<or=80 mm Hg (5.5% vs 2.8%; P=0.004). PP more than 80 mm Hg was also found
      to be associated with cardiac complications, increasing the incidence of
      congestive heart failure by 52%, and death from cardiac cause by nearly 100%
      (P=0.003 and 0.006, respectively). CONCLUSION: An increase in PP was
      independently and significantly associated with greater fatal and nonfatal
      adverse cerebral and cardiac outcomes in patients having CABG surgery. These
      findings highlight the associated risks of preoperative PP on acute postoperative
      vascular outcomes.

PMID- 18806015
TI  - Etomidate has no effect on hypoxia reoxygenation and hypoxic preconditioning in
      isolated human right atrial myocardium.
AB  - BACKGROUND: We examined the effects of etomidate on recovery of contractile
      function after hypoxia reoxygenation and hypoxic preconditioning in vitro using
      isolated human myocardium. METHODS: Human right atrial myocardium were obtained
      at the time of cardiac surgery from 38 adults patients. We recorded isometric
      force of contraction (FoC) of atrial trabeculae suspended in an oxygenated
      Tyrode's solution (34 degrees C, stimulation frequency 1 Hz). In all groups, a 30
      min hypoxic period was followed by 60 min of reoxygenation (HR). In separate
      groups, muscles were exposed to etomidate (10(-7), 10(-6), 10(-5) M) 10 min
      before and throughout the HR periods. Hypoxic preconditioning was induced by 4
      min hypoxia followed by 7-min reoxygenation applied before HR periods. Etomidate
      10(-5) M was administered before, throughout, and after the hypoxic
      preconditioning stimulus. Recovery of FoC (expressed as % of baseline value) at
      the end of HR was compared among groups. RESULTS: Compared with the control group
      (FoC: 52%+/-10%), etomidate 10(-7) M (FoC: 57%+/-9%; P=0.24), 10(-6) M (FoC:
      61%+/-11%; P=0.10), and 10(-5) M (FoC: 54%+/-9%; P=0.29) did not modify the
      recovery of FoC after HR. Hypoxic preconditioning-induced increase in the
      recovery of FoC (87%+/-5%; P<0.001 vs control group) was not modified in the
      presence of etomidate 10(-5) M (FoC: 86%+/-7%; P=0.74 vs hypoxic preconditioning
      group). CONCLUSIONS: Etomidate did not modify the in vitro FoC of human
      myocardium exposed to HR. Furthermore, etomidate did not modify the protective
      effect of hypoxic preconditioning.

PMID- 18806016
TI  - Moderate acute isovolemic hemodilution alters myocardial function in patients
      with coronary artery disease.
AB  - BACKGROUND: Although moderate hemodilution is usually well tolerated in coronary
      artery surgery patients, this may not be the case when myocardial oxygen demand
      is increased. We hypothesized that, in these patients, hemodilution in the
      presence of an increased heart rate could be associated with an impairment of
      myocardial function. METHODS: Forty coronary surgery patients were randomly
      assigned to two groups (n=20), according to the rate of atrioventricular pacing
      [70 bpm (Group 70) or 90 bpm (Group 90)]. While paced at the fixed heart rate,
      hemodilution was performed before the start of cardiopulmonary bypass. Data were
      obtained from a pulmonary artery, a PiCCO catheter and a left ventricular
      pressure catheter. Measurements were obtained in steady-state conditions before
      and after isovolemic hemodilution. RESULTS: Hemodilution from 40%+/-2% to 30%+/
      1% in Group 70, and from 39%+/-4% to 30%+/-2% in Group 90 resulted in a decrease
      in systemic vascular resistance and an increase in end-diastolic volume in both
      groups. This was associated with an increase in stroke volume in Group 70 but not
      in Group 90. In this latter group, the maximal rate of pressure development
      decreased significantly after hemodilution [from 856+/-93 to 716+/-80 mm Hg/s
      (P<0.01)], whereas it remained unchanged in Group 70 (843+/-86 mm Hg/s before and
      832+/-79 mm Hg/s after hemodilution). CONCLUSIONS: In the conditions of the
      present study, increased heart rate during moderate hemodilution was associated
      with a depression of myocardial function.

PMID- 18806017
TI  - Left ventricular mass: intraoperative transesophageal echocardiography for
      evaluation and management.

PMID- 18806018
TI  - The use of transesophageal echocardiography in determining the structural and
      functional impact of traumatic intracardiac foreign bodies.

PMID- 18806019
TI  - Intraoperative monitoring of movement of an entrapped coronary guidewire by
      transesophageal echocardiography.

PMID- 18806020
TI  - An unusual giant right coronary artery aneurysm resembles an intracardiac mass.

PMID- 18806021
TI  - Coronary sinus atrial septal defect.

PMID- 18806022
TI  - Diastolic regurgitation through a bi-leaflet mechanical valve in the mitral
      position.

PMID- 18806023
TI  - Intraoperative low-dose ketamine does not prevent a remifentanil-induced increase
      in morphine requirement after pediatric scoliosis surgery.
AB  - BACKGROUND: Remifentanil-based anesthesia is commonly used to facilitate
      neurophysiologic monitoring during pediatric scoliosis surgery. Acute opioid
      tolerance and/or hyperalgesia resulting from remifentanil-based anesthesia may
      involve activation of N-methyl-D-aspartate systems. We hypothesized that low-dose
      intraoperative infusion of the N-methyl-d-aspartate antagonist ketamine would
      suppress the development of tolerance and thereby decrease postoperative morphine
      consumption in children receiving remifentanil-based anesthesia for scoliosis
      surgery. METHODS: Thirty-four adolescents aged 12-18 yr scheduled for scoliosis
      surgery were randomly assigned to receive intraoperative low-dose ketamine (bolus
      dose of 0.5 mg/kg followed by continuous infusion of 4 microg.kg(-1).min(-1)) or
      an equal volume of saline during propofol/remifentanil anesthesia. Cumulative
      morphine consumption was assessed using a patient-controlled analgesia device for
      72 h after surgery. Postoperative morphine consumption, pain scores at rest and
      during cough, and sedation scores were recorded by a blinded investigator every
      hour for the first 4 h, every 4 hours for 20 h, and then every 12 hours for 72 h.
      RESULTS: Cumulative morphine consumption at 24, 48, and 72 h after surgery did
      not differ significantly between groups (ketamine group: 1.57+/-0.56, 3.05+/
      1.14, and 4.46+/-1.53 mg/kg; saline group: 1.60+/-0.53, 2.87+/-1.05, and 4.11+/
      1.71 mg/kg, respectively). No differences in pain or sedation scores were found.
      The duration of anesthesia was similar in the two groups. CONCLUSIONS: These data
      do not support the use of intraoperative low-dose ketamine to prevent the
      development of remifentanil-induced acute opioid tolerance and/or hyperalgesia
      during pediatric scoliosis surgery.

PMID- 18806024
TI  - The effect of intranasal administration of remifentanil on intubating conditions
      and airway response after sevoflurane induction of anesthesia in children.
AB  - BACKGROUND: Intubation without the use of muscle relaxants in children is
      frequently done before IV access is secured. In this randomized controlled trial,
      we compared intubating conditions and airway response to intubation (coughing
      and/or movement) after sevoflurane induction in children at 2 and 3 min after the
      administration of intranasal remifentanil (4 mcg/kg) or saline. METHODS: One
      hundred eighty-eight children, 1-7-yr old, were studied. Nasal remifentanil (4
      mcg/kg) or saline was administered 1 min after an 8% sevoflurane N2O induction.
      The sevoflurane concentration was then reduced to 5% in oxygen, and ventilation
      assisted/controlled. An anesthesiologist blinded to treatment assignment used a
      validated score to evaluate the conditions for laryngoscopy and response to
      intubation. Blood samples for determination of remifentanil blood concentrations
      were collected from 17 children at baseline, 2, 3, 4, and 10 min after nasal
      administration of remifentanil. RESULTS: Good or excellent intubating conditions
      were achieved at 2 min (after the remifentanil bolus) in 68.2% and at 3 min in
      91.7% of the children who received intranasal remifentanil versus 37% and 23% in
      children who received placebo (P<0.01). The mean remifentanil plasma
      concentrations (+/-sd) at 2, 3, 4, and 10 min were 1.0 (0.60), 1.47 (0.52), 1.70
      (0.46), and 1.16 (0.36) ng/mL, respectively. Peak plasma concentration was
      observed at 3.47 min. There were no complications associated with the use of
      nasal remifentanil. CONCLUSIONS: Nasal administration of remifentanil produces
      good-to-excellent intubating conditions in 2-3 min after sevoflurane induction of
      anesthesia.

PMID- 18806025
TI  - Pharmacokinetics of levobupivacaine (2.5 mg/kg) after caudal administration in
      children younger than 3 years.
AB  - BACKGROUND: Caudal administration of levobupivacaine (2.5 mg/kg) in children is
      used frequently in some hospitals. However, no reports of levobupivacaine
      concentrations have been published with this dosing scheme. We report the results
      of a study on the pharmacokinetics of levobupivacaine (2.5 mg/kg) after caudal
      administration in children younger than 3 yr. METHODS: Ten children, aged 1-36 mo
      and scheduled for subumbilical surgery were studied under sevoflurane anesthesia.
      After caudal injection of 0.25% levobupivacaine (2.5 mg/kg), serial venous blood
      samples were taken for 3 h to measure total plasma concentration levels of
      levobupivacaine. Median (range) levobupivacaine Cmax and Tmax measured were 1.48
      (0.62-2.40) microg/mL and 37 (10-60) min. The highest individual Cmax was
      observed in a 1-mo-old infant 30 min after caudal block. CONCLUSIONS: The highest
      Cmax reached in this study was close to the toxic threshold of adult patients.
      Although no adverse events have been reported, care must be taken, especially in
      small infants, after caudal administration of levobupivacaine (2.5 mg/kg).

PMID- 18806026
TI  - ABO-incompatible blood transfusion and invasive therapeutic approaches during
      pediatric cardiopulmonary bypass.
AB  - Human error has been identified as a major source of ABO-incompatible blood
      transfusion which most often results from blood being given to the wrong patient.
      We present a case of inadvertent administration of ABO-incompatible blood to a 6
      mo-old child who underwent congenital heart surgery and discuss the use of
      invasive therapeutic approaches. Invasive techniques included total circulatory
      arrest and large-volume exchange transfusion, along with conventional
      ultrafiltration and plasmapheresis, which could all be performed rapidly and
      effectively. The combination of standard pharmacologic therapies and alternative
      invasive techniques after a massive ABO-incompatible blood transfusion led to a
      favorable outcome in our patient.

PMID- 18806027
TI  - Psychometric testing of the Chinese quality of recovery score.
AB  - BACKGROUND: We evaluated a Chinese translation of the quality of recovery (QoR)
      score for measuring health status in patients after surgery and anesthesia.
      METHODS: The Chinese QoR score was developed by a panel of linguistic experts
      using a series of forward and backward translations. We then compared the
      psychometric performance of the Chinese QoR score with the original English
      version in bilingual Chinese patients undergoing a variety of surgeries. Using a
      crossover design, 210 patients were randomly assigned to complete both versions
      of the QoR score, 1 h apart, in the morning after surgery according to one of the
      two sequences: Chinese followed by the English QoR score or the reverse order.
      Test-retest and interrater reliabilities were calculated by comparing scores
      administered 6-8 h later and those completed by the patients and duty nurses,
      respectively. RESULTS: Patient responses to the Chinese QoR score agreed well
      with the English version (weighted kappa statistic, kappaw=0.92). Both QoR scores
      correlated with patient satisfaction scores (Chinese version, rho=0.82; English
      version, rho=0.79) confirming convergent validity. There was also significant
      negative correlation between the QoR scores and female gender, duration of
      hospital stay, or magnitude of surgery (discriminant construct validity). We
      found the Chinese QoR score has good internal consistency (Cronbach's rho=0.91),
      interobserver (kappaw=0.77), and test-retest reliability (kappaw=0.83). These
      values were similar to those of the original English version (Cronbach's
      rho=0.89, interobserver kappaw=0.84, test-retest reliability kappaw=0.88).
      CONCLUSION: The Chinese QoR score is conceptually, semantically, and
      operationally equivalent to the English version. Both scales provide valid,
      reliable, and responsive assessment of the QoR after surgery and anesthesia.

PMID- 18806028
TI  - The accuracy and clinical feasibility of a new bayesian-based closed-loop control
      system for propofol administration using the bispectral index as a controlled
      variable.
AB  - BACKGROUND: Closed-loop control of the hypnotic component of anesthesia has been
      proposed in an attempt to optimize drug delivery. Here, we introduce a newly
      developed Bayesian-based, patient-individualized, model-based, adaptive control
      method for bispectral index (BIS) guided propofol infusion into clinical practice
      and compare its accuracy and clinical feasibility under direct observation of an
      anesthesiologist versus BIS guided, effect compartment controlled propofol
      administration titrated by the anesthesiologist during ambulatory gynecological
      procedures. METHODS: Forty ASA patients were randomly allocated to the closed
      loop or manual control group. All patients received midazolam 1 mg IV and
      alfentanil 0.5 mg IV before induction. In the closed-loop control group, propofol
      was administered using the previously described closed-loop control system to
      reach and maintain a target BIS of 50. In the manual control group, the propofol
      effect-site concentration was adapted at the discretion of the anesthesiologist
      to reach and maintain a BIS as close as possible to 50. Induction
      characteristics, performance, and robustness during maintenance and recovery
      times were compared. Hemodynamic and respiratory stability were calculated as
      clinical feasibility parameters. RESULTS: The closed-loop control system titrated
      propofol administration accurately resulting in BIS values close to the set
      point. The closed-loop control system was able to induce the patients within
      clinically accepted time limits and with less overshoot than the manual control
      group. Automated control resulted in beneficial recovery times. Our closed-loop
      control group showed similar acceptable clinical performance specified by similar
      hemodynamic, respiratory stability, comparable movement rates, and quality scores
      than the manual control group. CONCLUSIONS: The Bayesian-based closed-loop
      control system for propofol administration using the BIS as a controlled variable
      performed accurate during anesthesia for ambulatory gynecological procedures.
      This control system is clinical feasibility and can be further validated in
      clinical practice.

PMID- 18806029
TI  - Spatial memory is intact in aged rats after propofol anesthesia.
AB  - BACKGROUND: We have previously demonstrated that aged rats have persistent
      impairment of spatial memory after sedation with nitrous oxide or general
      anesthesia with isoflurane-nitrous oxide. Propofol has different receptor
      mechanisms of action and a favorable short-term recovery profile, and it has been
      proposed that propofol is devoid of enduring effects on cognitive performance. No
      studies have investigated this question in aged subjects, however, so we designed
      an experiment to examine the long-term effects of propofol anesthesia on spatial
      working memory. METHODS: Eighteen-mo-old rats were randomized to 2 h of 100%
      oxygen-propofol anesthesia (n=11) or to a control group that breathed 100% oxygen
      (n=10). Propofol was administered by continuous infusion via a tail vein
      catheter. Rats breathed spontaneously and rectal temperature was maintained. Mean
      arterial blood pressure was measured noninvasively and a venous blood gas was
      obtained just before discontinuation of propofol. After a 2-day recovery, spatial
      working memory was assessed for 14 days using a 12-arm radial maze. The number of
      total errors, number of correct choices to first error, and time to complete the
      maze was recorded and analyzed using a repeated measure analysis of variance
      (ANOVA), with P<0.05 being considered statistically significant. RESULTS: The
      average propofol infusion rate was 0.6+/-0.1 mg.kg (-1).min(-1), a rate
      corresponding to a 50% effective concentration dose in adult rats. Mean arterial
      blood pressure during anesthesia was 100+/-2 mm Hg and venous blood gases
      remained in the normal range. There was no difference between the control and
      previously anesthetized rats on any measure of radial arm maze performance,
      indicating propofol anesthesia produces no lasting impairment in spatial working
      memory in aged rats. CONCLUSIONS: In aged rats, propofol anesthesia is devoid of
      the persistent memory effects observed with other general anesthetics in this
      model. Thus, while it appears that the state of general anesthesia is neither
      necessary nor sufficient for development of postanesthetic memory impairment, the
      choice of anesthetics may play a role in late cognitive outcome in the aged.

PMID- 18806030
TI  - The effect of amitriptyline, gabapentin, and carbamazepine on morphine-induced
      hypercarbia in rabbits.
AB  - BACKGROUND: Severe exacerbation of chronic neuropathic pain often requires
      morphine in patients already treated with drugs such as tricyclic
      antidepressants, carbamazepine and gabapentin. However, it is unclear if a
      combination of these drugs intensifies the effects of morphine on the respiratory
      system and, if so, whether these effects are due to pharmacokinetic or
      pharmacodynamic interaction. METHODS: We gave rabbits (n=6 per group) the
      following drugs daily for 4 days: subcutaneous normal saline 1 mL (control);
      amitriptyline subcutaneously 7 mg/kg; carbamazepine orally 100 mg/kg; gabapentin
      subcutaneously 25 mg/kg; and all three drugs concurrently (combination). On the
      fifth day, morphine 5 mg/kg was given IV, and Paco2, Pao2 and pH were measured.
      Morphine, morphine 3-glucoronide and morphine 6-glucoronide concentrations were
      measured in the plasma over the 4 h period after morphine injection. RESULTS:
      Compared with controls, premorphine baseline Paco2 was significantly higher
      (P<0.05) in the amitriptyline group. Postmorphine Paco2 was significantly higher
      in the amitriptyline and combination groups at all time points over the 240 min,
      and in the gabapentin group at 10 and 30 min after morphine injection (P<0.05).
      Peak Paco2 was significantly higher in the amitriptyline group (58.4+/-1.6 mm Hg;
      mean SD, P<0.005) and in the combination group (57.4+/-1.0 mm Hg, P<0.02) than in
      the control group (50.2+/-5.2 mm Hg). Similarly, the area under the curve of
      Paco2 from zero to 240 min was significantly higher in the amitriptyline and
      combination groups than in the control (P<0.001). There were no significant
      differences among the groups in plasma concentrations of morphine and its
      metabolites. CONCLUSIONS: We conclude that pretreatment with amitriptyline
      increases morphine- induced hypercarbia through pharmacodynamic processes. The
      effects of carbamazepine or gabapentin were not obvious in this model.

PMID- 18806031
TI  - Noble gas binding to human serum albumin using docking simulation:
      nonimmobilizers and anesthetics bind to different sites.
AB  - BACKGROUND: Nonimmobilizers are structurally similar to anesthetics, but do not
      produce anesthesia at clinically relevant concentrations. Xenon, krypton, and
      argon are anesthetics, whereas neon and helium are nonimmobilizers. The
      structures of noble gases with anesthetics or nonimmobilizers are similar and
      their interactions are simple. Whether the binding site of anesthetics differs
      from that of nonimmobilizers has long been a question in molecular
      anesthesiology. METHODS: We investigated the binding sites and energies of
      anesthetic and nonimmobilizer noble gases in human serum albumin (HSA) because
      the 3D structure of HSA is well known and it has an anesthetic binding site. The
      computational docking simulation we used searches for binding sites and
      calculates the binding energy for small molecules and a template molecule.
      RESULTS: Xenon, krypton, and argon were found to bind to the enflurane binding
      site of HSA, whereas neon and helium were found to bind to sites different from
      the xenon binding site. Rare gas anesthetic binding was dominated by van der
      Waals energy, while nonimmobilizer binding was dominated by solvent-effect
      energy. Binding site preference was determined by the ratios of local binding
      energy (van der Waals energy) and nonspecific binding energy (solvent-effect
      energy) to the total binding energy. van der Waals energy dominance is necessary
      for anesthetic binding. CONCLUSIONS: This analysis of binding energy components
      provides a rationale for the binding site difference of anesthetics and
      nonimmobilizers, reveals the differences between the binding interactions of
      anesthetics and nonimmobilizers, may explain pharmacological differences between
      anesthetics and nonimmobilizers, and provide an understanding of anesthetic
      action at the atomic level.

PMID- 18806032
TI  - The inhibition of human neutrophil phagocytosis and oxidative burst by tricyclic
      antidepressants.
AB  - BACKGROUND: Tricyclic antidepressants are being investigated as long-acting
      analgesics for topical application in wounds or IV for postoperative pain relief.
      However, it remains unclear if tricyclic antidepressants affect the host defense
      and if reported toxic effects on neutrophils are of relevance in this setting. We
      therefore investigated the effects of amitriptyline, nortriptyline, and
      fluoxetine on human neutrophil phagocytosis, oxidative burst, and neutrophil
      toxicity in a human whole blood model. METHODS: Heparinized blood samples from
      healthy volunteers were incubated with amitriptyline, nortriptyline, or
      fluoxetine (10(-6) to 10(-3) M) for 0, 1, or 3 h. Staphylococcus aureus in a
      bacteria:neutrophil ratio of 5:1 and dihydroethidium (for the determination of
      oxidative burst) were added. Phagocytosis was stopped after 5, 10, 20, and 40
      min. After lysis of red blood cells, samples were analyzed by flow cytometry.
      RESULTS: In concentrations up to 10(-4) M, none of the compounds affected
      neutrophil phagocytosis and oxidative burst. At 10(-3) M, all three compounds
      were highly toxic for neutrophils. Amitriptyline preserved morphological
      integrity, but completely suppressed neutrophil function. Nortriptyline and
      fluoxetine caused a marked disruption of neutrophils. The effects of the
      investigated antidepressants were not time-dependent. CONCLUSIONS: Phagocytosis
      and intracellular host defense are largely unaffected by antidepressants in
      concentrations of 10(-4) M and below. Our results confirm that antidepressants
      are highly toxic to neutrophils in millimolar concentrations. The neurotoxic
      effects and clinical side effects, but not effects on neutrophil functions,
      therefore, are likely to be the limiting factors in using antidepressants as
      analgesics.

PMID- 18806033
TI  - The effect of lidocaine on cholinergic neurotransmission in an identified
      reconstructed synapse.
AB  - BACKGROUND: The presynaptic effect of lidocaine on cholinergic synaptic
      transmission is unclear because of the difficulty in identifying presynaptic
      neurons and the complexity of the central nervous system in vivo. To clarify the
      effect of lidocaine on cholinergic synapse, we reconstructed a cultured soma-soma
      chemical synapse model consisting of two identified visceral dorsal 4 (VD4) and
      left pedal e-1 (LPeD1) neurons from the snail, Lymnaea stagnalis, in vitro, and
      used it to determine how lidocaine affects cholinergic synaptic transmission.
      METHODS: The response to acetylcholine and excitatory postsynaptic potential
      (EPSP) amplitude was recorded in the reconstructed chemical synaptic transmission
      model composed of VD4 and LPeD1 neurons. The currents for acetylcholine
      measurements were made under voltage-clamp in the presynaptic VD4 and
      postsynaptic LPeD1 neurons. RESULTS: Lidocaine inhibited both EPSP and the
      response for acetylcholine of the postsynaptic neuron. EPSP amplitude was reduced
      in a voltage-dependent manner in the presynaptic neuron, and lidocaine induced a
      hyperpolarization shift of the voltage-dependent inactivation curves of EPSP
      amplitude. CONCLUSIONS: Lidocaine inhibits cholinergic synaptic transmission with
      a voltage-dependent inactivation of EPSP amplitude through the membrane potential
      depolarization of presynaptic neurons.

PMID- 18806034
TI  - Assessment of asymmetric lung disease in intensive care unit patients using
      vibration response imaging.
AB  - BACKGROUND: Vibration response imaging (VRI) is a computer-based technology that
      creates a visual dynamic two-dimensional image of distribution of vibration
      within the lung during the respiratory process. The acoustic signals, recorded
      from 36 posteriorly positioned surface skin sensors, are transferred to a
      hardware board where several stages of filtering are applied to select a specific
      frequency band. The filtered output signal frequencies are presented as a gray
      scale coded dynamic image, consisting of a series of 0.17 s frames, and as a
      table featuring the percentage contribution of each lung to the total vibration
      signal. METHODS: We describe the VRI technology in detail and examine images
      obtained from consecutive intensive care unit (ICU) patients with one diseased
      lung on chest radiograph. ICU patients with normal chest radiographs are
      presented as controls. Analysis of the image was performed by comparing the
      weighted pixel count analysis from both lungs. In this method, the pixels in the
      image were assigned values based on their grayscale color with the darker pixels
      assigned higher values. RESULTS: In patients with normal chest radiographs, the
      right and left lungs developed similarly in dynamic VRI images, and the percent
      lung vibrations from both sides were comparable (53%+/-12% and 47%+/-12%,
      respectively). In ICU patients with asymmetric lung disease, however, the percent
      lung vibrations from the diseased and nondiseased lungs were 27%+/-23% and 73%+/
      23%, respectively (P<0.001). In patients with asymmetric lung disease (one lung
      has moderate to severe disease and the other appears normal or close to normal as
      per chest radiograph), the diseased lung usually appeared in VRI as irregular,
      smaller, and lighter in color (reduced vibration signal) when compared to the
      nonaffected lung. The weighted pixel count from diseased and nondiseased lungs
      were 33%+/-21% and 67%+/-21%, respectively (P < 0.003). CONCLUSION: The VRI
      technology may provide a radiation-free method for identifying and tracking of
      asymmetric lung parenchymal processes.

PMID- 18806035
TI  - A new curved laryngoscope blade for routine and difficult tracheal intubation.
AB  - We have designed a new curved laryngoscope blade based on a new concept of
      reversing the peardrop phenomenon to facilitate a view of the larynx sufficient
      for intubation in a greater variety of patients than the current Macintosh blade
      affords. The new design has a bifid tip and S-shaped spatula to exert more
      effective pressure in the vallecula area, elevate the epiglottis and change
      directions of the forces on the tongue to prevent posteroinferior displacement of
      the compressed tongue in the submandibular space during laryngoscopy. A
      radiograph laryngoscopy technique was used to guide the new blade curvature
      design and compare the performance of the new blade with the Macintosh blade in
      patients with or without a difficult airway. Our results confirm that the new
      blade provides a laryngeal view sufficient to accomplish intubation by
      compressing the root of the tongue in an anterocephalad direction in the
      submandibular space and elevating the epiglottis effectively in patients with or
      without unanticipated difficult airway. The new curved blade can also effectively
      move the U-shaped epiglottis out of the laryngeal view to facilitate intubation
      in pediatric patients aged 2 mo-13 yr.

PMID- 18806036
TI  - Gum elastic bougie-guided insertion of the ProSeal laryngeal mask airway is
      superior to the digital and introducer tool techniques in patients with simulated
      difficult laryngoscopy using a rigid neck collar.
AB  - BACKGROUND: We compared three techniques for insertion of the laryngeal mask
      airway ProSeal (PLMA) in patients with simulated difficult laryngoscopy using a
      rigid neck collar. METHODS: Ninety-nine anesthetized healthy female patients aged
      19-68 yr were randomly allocated for PLMA insertion using the digital, introducer
      tool (IT) or guided techniques. Difficult laryngoscopy was simulated using a
      rigid neck collar. The laryngoscopic view was graded before PLMA insertion. The
      digital and IT techniques were performed according to the manufacturer's
      instructions. The guided technique involved priming the drain tube with an
      Eschmann tracheal tube introducer, placing the introducer in the esophagus under
      direct vision and railroading the PLMA into position. Failed insertion was
      defined by any of the following criteria: 1) failed pharyngeal placement, 2)
      malposition, and 3) ineffective ventilation. RESULTS: The median laryngoscopic
      view was 3 and the mean interincisor distance was 3.3 cm. Insertion was more
      frequently successful with the guided technique at the first attempt (guided
      100%, digital 64%, IT 61%; P<0.0001), but success after three attempts was
      similar (guided 100%, digital 94%, IT 91%). The time taken for successful
      placement was similar among groups at the first attempt, but was shorter for the
      guided technique after three attempts (guided 31+/-8 s, digital 49+/-28 s, IT
      54+/-37 s; P<0.02). CONCLUSION: The guided insertion technique is more frequently
      successful than the digital or IT techniques in patients with simulated difficult
      laryngoscopy using a rigid neck collar.

PMID- 18806037
TI  - The risk of pulmonary aspiration in patients after weight loss due to bariatric
      surgery.
AB  - BACKGROUND: We conducted a study including patients with gastric banding or
      gastroplasty who previously underwent plastic or functional surgery to assess the
      risk of pulmonary aspiration. METHODS: A retrospective case-control study was
      performed including all patients undergoing a plastic or functional surgery over
      a 5-yr period (2000-2005) at Rouen University Hospital. Two groups were defined:
      the postbariatric group included patients who previously had bariatric surgery
      (laparoscopic adjustable gastric banding or Mason's vertical gastroplasty) before
      undergoing the plastic surgery; all other patients were assigned to the control
      group. Data included all anesthetic management and were recorded in the hospital
      computer database. The incidence of pulmonary aspiration was the outcome
      variable. RESULTS: One hundred ninety-eight plastic and functional operations (66
      cases and 132 controls) were performed. Pulmonary aspiration was significantly
      (P<0.006) higher in the postbariatric group (4 patients: 6%) than in the
      nonbariatric group (0 patient). For this complication, all patients had
      previously undergone gastric banding. One patient who did not receive prokinetic
      prophylaxis required intensive care for severe pulmonary alteration. CONCLUSION:
      The risk of perioperative pulmonary aspiration in a patient after weight loss due
      to gastric banding was considered significant.

PMID- 18806038
TI  - Bronchospasm after intravenous lidocaine.
AB  - IV lidocaine (1.5 mg/kg) administered to facilitate endotracheal intubation was
      associated with transient bronchospasm in a 17-month-old-female with mild
      intermittent asthma. Immediately after lidocaine administration, the patient
      developed diffuse bilateral expiratory wheezes and dramatic increases in peak
      inspiratory pressure. Over approximately 5 min the episode resolved and an
      uneventful anesthetic course followed. This is consistent with recent clinical
      studies suggesting that IV lidocaine may cause airway narrowing in asthmatics.
      Practitioners should be aware of this potential complication.

PMID- 18806039
TI  - Pulmonary cytokine responses during mechanical ventilation of noninjured lungs
      with and without end-expiratory pressure.
AB  - BACKGROUND: Positive end-expiratory pressure (PEEP) during mechanical ventilation
      may impose different degrees of stress on healthy lungs. On the assumption that
      stress is reflected by cytokine production, we performed a translational study
      investigating the effect of PEEP on bronchoalveolar and systemic mediator levels
      in isolated perfused mouse lungs (IPL) and in patients with healthy lungs.
      METHODS: (Part I) IPL were ventilated with end-expiratory pressures of 0, 3, 6,
      or 10 cm H2O and end-inspiratory pressure (EIP) levels of 10 or 25 cm H2O.
      Interleukin (IL)-6 and macrophage inflammatory protein-2 concentrations in the
      venous effluate were monitored. (Part II) Patients (nonsmokers) scheduled for
      elective otorhinolaryngology surgery (duration>90 min) were randomized to receive
      either ventilation with zero end-expiratory pressure or PEEP (10 cm H2O).
      Mediators in bronchoalveolar lavage, nuclear factor kappaB, (NF-kappaB)
      activation in alveolar macrophages and circulating systemic mediators were
      monitored. Control patients underwent bronchoalveolar lavage after intubation.
      RESULTS: In the IPL, mediator concentrations increased with increasing end
      expiratory pressure at an EIP of 10 cm H2O, but decreased at 25 cm H2O EIP. In
      patients, bronchoalveolar IL-6, monocyte chemoattractant protein-1, and
      granulocyte monocyte-colony stimulating factor were increased by ventilation
      regardless of the PEEP level. IL-6 and IL-8 levels were moderately increased by
      PEEP but not zero end-expiratory pressure. Nuclear factor kappaB DNA binding
      activity in alveolar macrophages and systemic mediator levels did not change.
      CONCLUSIONS: On the basis of the premise that cytokine levels may indicate
      mechanical stress, our findings indicate that even low tidal volume ventilation
      causes some stress. PEEP is beneficial at high inspiratory pressure, but imposes
      moderate stress at low inspiratory pressure.

PMID- 18806040
TI  - Production of endothelin-1 and reduced blood flow in the rat kidney during lung
      injurious mechanical ventilation.
AB  - INTRODUCTION: The mechanisms by which mechanical ventilation (MV) can injure
      remote organs, such as the kidney, remain poorly understood. We hypothesized that
      upregulation of systemic inflammation, as reflected by plasma interleukin-6 (IL
      6) levels, in response to a lung-injurious ventilatory strategy, ultimately
      results in kidney dysfunction mediated by local endothelin-1 (ET-1) production
      and renal vasoconstriction. METHODS: Healthy, male Wistar rats were randomized to
      1 of 2 MV settings (n=9 per group) and ventilated for 4 h. One group had a lung
      protective setting using peak inspiratory pressure of 14 cm H2O and a positive
      end-expiratory pressure of 5 cm H2O; the other had a lung-injurious strategy
      using a peak inspiratory pressure of 20 cm H2O and positive end-expiratory
      pressure of 2 cm H2O. Nine randomly assigned rats served as nonventilated
      controls. We measured venous and arterial blood pressure and cardiac output
      (thermodilution method), renal blood flow (RBF) using fluorescent microspheres,
      and calculated creatinine clearance, urine flow, and fractional sodium excretion.
      Histological lung damage was assessed using hematoxylin-eosin staining. Renal ET
      1 and plasma ET-1 and IL-6 concentrations were measured using enzyme-linked
      immunosorbent assays. RESULTS: Lung injury scores were higher after lung
      injurious MV than after lung-protective ventilation or in sham controls. Lung
      injurious MV resulted in significant production of renal ET-1 compared with the
      lung-protective and control groups. Simultaneously, RBF in the lung-injurious MV
      group was approximately 40% lower (P<0.05) than in the control group and 28%
      lower (P<0.05) than in the lung-protective group. Plasma ET-1 and IL-6 levels did
      not differ among the groups and systemic hemodynamics, such as cardiac output,
      were comparable. There was no effect on creatinine clearance, fractional sodium
      excretion, urine output, or kidney histology. CONCLUSIONS: Lung-injurious MV for
      4 h in healthy rats results in significant production of renal ET-1 and in
      decreased RBF, independent of IL-6. Decreased RBF has no observable effect on
      kidney function or histology.

PMID- 18806041
TI  - Propofol attenuates the decrease of dynamic compliance and water content in the
      lung by decreasing oxidative radicals released from the reperfused liver.
AB  - BACKGROUND: Remote pulmonary injuries after hepatic reperfusion are frequently
      caused by reactive oxygen species (ROS)-induced damage. The choice of anesthetics
      may affect the balance between oxidants and antioxidants, and propofol, a
      commonly used anesthetic, has an antioxidant effect. In this study, we developed
      a model to study pulmonary function with hepatic ischemia/reperfusion (I/R)
      manipulation, with the aim of defining remote pulmonary dysfunction after hepatic
      reperfusion and determining if propofol affects this dysfunction by altering ROS
      production from the liver or lungs. METHODS: Adult male rats weighing 160-250 g
      were randomly divided into four groups according to the type of surgery (sham or
      I/R) and the anesthetic administered (pentobarbital or propofol). To induce I/R,
      the portal vein and hepatic artery to the left and medial lobes of the liver were
      clamped. All of the measurements were done after 5 h of reperfusion, after 45 min
      of ischemia. Pulmonary function after hepatic I/R was determined by dynamic
      compliance, resistance and wet-to-dry ratio, and by histopathology. Hepato
      cellular injuries were confirmed by alanine aminotransferase, whereas ROS
      production was measured from the inferior vena cava, jugular vein, and carotid
      artery. Products of lipid peroxidation, thiobarbiturate acid reactive substances
      and malondialdehyde, were measured in lung and hepatic tissues. RESULTS: Remote
      lung injury after hepatic I/R was shown by a significant decrease of Cdyn, and
      increases in resistance and the wet-to-dry ratio. ROS production was
      significantly increased and was highest in samples from the inferior vena cava.
      Thiobarbiturate acid reactive substances and malondialdehyde in the liver and
      serum alanine aminotransferase were significantly increased only in the
      I/R+pentobarbital group. All of the changes were significantly attenuated in the
      I/R+ propofol group (P=0.05). With propofol infusion, there was decreased ROS
      production from the reperfused liver, with less hepato-cellular injury, followed
      by well-maintained pulmonary function. CONCLUSION: Remote pulmonary dysfunction
      and reperfusion injury in the liver were demonstrated in our rat model, as well
      as massive ROS production and lipid peroxidation. Propofol infusion attenuated
      remote pulmonary injury by lessening oxidative injury from the reperfused liver.

PMID- 18806042
TI  - Composite auditory evoked potential index versus bispectral index to estimate the
      level of sedation in paralyzed critically ill patients: a prospective
      observational study.
AB  - BACKGROUND: Electromyographic activity (EMG) has been reported to elevate the
      Bispectral Index (BIS) in patients not receiving neuromuscular blockade while
      under sedation in the intensive care unit (ICU). We investigated the change of
      the composite A-line autoregressive index (AAI) and BIS after administration of
      muscle relaxants in sedated surgical ICU patients. METHODS: We prospectively
      investigated 38 patients who required administration of a muscle relaxant while
      continuously sedated with midazolam hydrochloride and fentanyl citrate to achieve
      a Ramsay Sedation Scale value equal to 5. BIS, EMG activity of BIS (EMG-BIS),
      signal quality index of BIS, AAI, EMG activity of AAI (EMG-AAI), and
      acceleromyography at the adductor pollicis muscle were recorded simultaneously
      every 5 min for 30 min before and after neuromuscular blockade. Student's t-test,
      the Wilcoxon's signed ranks test, and the Spearman test were calculated using the
      standard statistics software SPSS 10.0 (SPSS Inc., Chicago, IL). RESULTS: After
      administration of a muscle relaxant, BIS (58.61+/-7.45 vs 44.68+/-6.65, P<0.001),
      EMG-BIS (37.33+/-7.15 vs 27.24+/-1.51, P<0.001), AAI (34.11+/-10.96 vs 15.97+/
      6.69, P<0.001), and EMG-AAI (59.58+/-9.57 vs 1.00+/-0.00, P<0.001) decreased
      significantly. Significant correlations between BIS and EMG-BIS (rs=0.75,
      P<0.001) and AAI and EMG-AAI (rs=0.87, P<0.001) were also found during the
      baseline period. CONCLUSIONS: This study demonstrated that, in sedated ICU
      patients, BIS and AAI markedly decreased after administration of myorelaxant, and
      the decreased BIS and AAI values after neuromuscular blockade were correlated to
      those usually seen in the state of surgical anesthesia, respectively.

PMID- 18806043
TI  - A randomized double-blinded comparison of phenylephrine and ephedrine infusion
      combinations to maintain blood pressure during spinal anesthesia for cesarean
      delivery: the effects on fetal acid-base status and hemodynamic control.
AB  - BACKGROUND: Phenylephrine and ephedrine are both used to maintain arterial blood
      pressure during spinal anesthesia for cesarean delivery. Usually, either drug is
      given alone but several previous studies have described combining the drugs.
      However, the effect of varying the proportion of vasopressors in such
      combinations has not been reported. METHODS: One-hundred-twenty-five parturients
      having spinal anesthesia for elective cesarean delivery were randomized to
      receive an IV infusion of phenylephrine and ephedrine combined in one of five
      different concentration ratios. Assuming phenylephrine 100 microg to be
      approximately equipotent to ephedrine 8 mg, the groups contained the proportional
      potency equivalent of 100%, 75%, 50%, 25% or 0% of phenylephrine and 0%, 25%,
      50%, 75% or 100%, respectively, of ephedrine. The infusions were adjusted to
      maintain systolic blood pressure (SBP) near baseline until uterine incision.
      Hemodynamic changes and umbilical cord blood gases were compared. RESULTS: As the
      proportion of phenylephrine decreased and proportion of ephedrine increased among
      the groups, the following significant trends were detected: the incidences of
      hypotension and nausea/vomiting increased, the median magnitude of deviations of
      SBP above or below baseline and the bias for SBP to be above baseline increased,
      maternal heart rate was faster, fetal pH and base excess decreased, umbilical
      arterial oxygen content decreased and umbilical venous Po2 increased.
      CONCLUSIONS: When varying combinations of phenylephrine and ephedrine were given
      by infusion to maintain arterial blood pressure during spinal anesthesia for
      cesarean delivery, as the proportion of phenylephrine decreased and the
      proportion of ephedrine increased, hemodynamic control was reduced and fetal acid
      base status was less favorable. Combinations of phenylephrine and ephedrine
      appear to have no advantage compared with phenylephrine alone when administered
      by infusion for the prevention of hypotension associated with spinal anesthesia
      for cesarean delivery.

PMID- 18806044
TI  - A comparison of the inhibitory effects of bupivacaine and levobupivacaine on
      isolated human pregnant myometrium contractility.
AB  - BACKGROUND: Epidural analgesia with levobupivacaine and bupivacaine is a common
      and effective method of labor pain relief. However, its use is associated with an
      increased instrumental delivery rate. One of the mechanisms postulated to account
      for this unwanted effect is the direct effect of local anesthetics on myometrial
      contractility. We determined the effects of bupivacaine and levobupivacaine on
      the amplitude and frequency of contractions of human term myometrium. METHODS:
      Uterine specimens were obtained from nonlaboring parturients scheduled for
      elective lower-segment cesarean delivery at term. Longitudinal muscle strips were
      prepared and mounted vertically in tissue chambers, and changes in the amplitude
      (peak force) and the frequency of contractions were recorded. Spontaneous
      contractions commenced after a period of application of 1 g (9.81 mN) of tension
      to the myometrial strips. No uterotonic drugs were used. The muscle strips were
      then exposed to cumulative concentrations of bupivacaine and levobupivacaine and
      dose-response curves were generated. RESULTS: Both bupivacaine and
      levobupivacaine decreased the amplitude of contractions in human myometrium in a
      concentration-dependent manner, reaching significance at 1x10(-4) M for both
      bupivacaine and levobupivacaine compared with the internal control amplitude.
      With both drugs, the decrease in amplitude was accompanied by an increase in the
      frequency of contractions reaching significance at 3x10(-5) M for both
      bupivacaine and levobupivacaine compared with the internal control frequency.
      CONCLUSIONS: The concentrations required for the effects on amplitude are much
      higher (33 fold) than the clinically relevant plasma concentrations of these
      drugs after epidural administration, and are unlikely to be significant in the
      setting of low-dose epidural analgesia in labor.

PMID- 18806045
TI  - P6 stimulation for the prevention of nausea and vomiting associated with cesarean
      delivery under neuraxial anesthesia: a systematic review of randomized controlled
      trials.
AB  - BACKGROUND: A number of studies investigated the use of P6 stimulation for the
      prevention of intraoperative and postoperative nausea and vomiting (IONV and
      PONV) in women having cesarean delivery under neuraxial anesthesia. We performed
      a systematic review to determine the overall efficacy of these techniques in
      preventing IONV and PONV in this patient population. METHODS: We performed a
      literature search of all randomized controlled trials (1966-2007) that compared
      different methods of P6 stimulation with placebo in women having cesarean
      delivery under neuraxial anesthesia. Data were extracted on the primary outcomes
      including the incidence of nausea, vomiting, and the need for rescue antiemetic
      therapy, both intraoperatively and postoperatively. RESULTS: Six studies
      involving 649 patients were included in this review. Five studies reported on
      intraoperative outcomes. Of these, two studies reported a significant reduction
      in the incidence of intraoperative nausea with P6 stimulation, and one study
      reported a significant reduction in rescue antiemetic requirement. However, none
      of the studies reported any differences between the treatment and control groups
      with respect to vomiting. Four studies reported postoperative outcomes. Of these,
      one study reported a significant reduction in postoperative nausea, two studies
      reported a significant reduction in postoperative vomiting, and one study
      reported a significant reduction in the need for postoperative rescue antiemetic
      therapy. CONCLUSIONS: While some studies showed a benefit of P6 stimulation, this
      finding was not consistent. The presence of heterogeneity and inconsistent
      results among the included trials prevents any definitive conclusions on the
      efficacy of P6 stimulation in reducing IONV and PONV associated with cesarean
      delivery performed under neuraxial anesthesia.

PMID- 18806046
TI  - Obstetric and anesthetic management of severe congenital myasthenia syndrome.
AB  - The congenital myasthenia syndromes form a heterogeneous group of genetic
      diseases characterized by defective neuromuscular transmission. Although they
      have muscle fatigability in common with the acquired immune myasthenia syndrome,
      there are important pathophysiological, diagnostic, management and progression
      pattern differences between them. We report the management of a 28-yr-old patient
      with longstanding congenital myasthenia syndromes, who underwent an elective
      cesarean delivery under spinal anesthesia. Muscle imbalance plus weakness-related
      scoliosis and chronic respiratory failure complicated her management.
      Ultrasonography was used to facilitate the spinal anesthetic. Intraoperative
      noninvasive positive pressure ventilation maintained lung volumes effectively and
      prevented deterioration in respiratory function.

PMID- 18806047
TI  - An instrument designed for faculty supervision evaluation by anesthesia residents
      and its psychometric properties.
AB  - BACKGROUND AND OBJECTIVES: We aimed 1) to develop a valid and reliable instrument
      for faculty supervision evaluation by anesthesia residents and 2) to disclose the
      sources of error in residents' ratings. METHODS: A qualitative study involving
      residents and faculty identified constructs of supervisory ability, which were
      entered as items in a measurement instrument used by 19 residents to evaluate 39
      instructors during a 6-mo period. The instrument was psychometrically tested
      under classical item and generalizability theories. A decision study, using the
      parameters of the generalizability (G) study, estimated the number of resident
      ratings needed to produce dependable measures of a single faculty. RESULTS: Nine
      dimensions emerged from the qualitative study: planning perianesthesia care,
      providing feedback ("the instructor provides me timely, informal, non-threatening
      comments on my performance and shows me ways to improve"); being available ("the
      instructor is promptly available to help me solve problems with patients and
      procedures"); giving opportunities/fostering resident autonomy; stimulating
      patient-based learning; demonstrating professionalism; being present during the
      critical events; demonstrating interpersonal skills; being concerned about
      safety. Residents provided 970 evaluations. The instrument exhibited internal
      consistency (Cronbach's alpha=0.93), content and face validities, and a single
      factor structure. Generalizability and dependability coefficients were 0.93.
      Between-instructors differences accounted for 56% of score variance. Resident
      instructor interactions accounted for 44% of score variance, indicating that
      scores were influenced by each resident's unique perceptions of instructors (halo
      effect). According to the results of the decision study, dependability of
      measures within the 75% to 95% range could be expected with 3 to 33 residents
      rating each faculty member, respectively. CONCLUSIONS: The nine-item instrument
      produced valid and reliable measures of faculty supervision. However, a
      significant amount of halo effect biased such measures. G-studies may help
      identify the type and magnitude of rater biases affecting resident-generated
      faculty supervision evaluations, and can be useful for interpreting their
      results, especially if personnel decisions (e.g., tenure, promotion) rely on such
      measures.

PMID- 18806048
TI  - Adoption of anesthesia information management systems by academic departments in
      the United States.
AB  - BACKGROUND: Information technology has been promoted as a way to improve patient
      care and outcomes. Whereas information technology systems for ancillary hospital
      services (e.g., radiology, pharmacy) are deployed commonly, it has been estimated
      that anesthesia information management systems (AIMS) are only installed in a
      small fraction of United States (US) operating rooms. In this study, we assessed
      the adoption of AIMS at academic anesthesia departments and explored the
      motivations for and resistance to AIMS adoption. METHODS: Members of the Society
      of Academic Anesthesiology Chairs and the Association of Anesthesiology Program
      Directors were solicited by e-mail to participate in an online survey of AIMS
      adoption. Two months after closing the survey, another e-mail was sent with a
      single question asking for an update to their AIMS implementation status.
      RESULTS: Surveys were fully completed by 48 (34%) of the 140 Society of Academic
      Anesthesiology Chairs and Association of Anesthesiology Program Directors
      departments surveyed, with 72 (51%) providing AIMS status information. Twenty of
      these 72 departments have an AIMS installed, 12 are currently implementing, 11
      have selected but not yet installed, and 18 are planning to purchase an AIMS in
      2008 or 2009. Therefore, at least 61 (44%) of all 140 US academic anesthesia
      departments have committed to AIMS. This estimated adoption rate is conservative
      because the numerator equals the affirmative responses, whereas the denominator
      equals the total population of academic departments. Among adopters, the top
      ranked anticipated benefits from installing an AIMS included improved clinical
      documentation, improved data collection for clinical research, enhancement of
      quality improvement programs, and compliance with requirements of regulatory
      authorities. The hospital provided funding in almost all facilities (90%), with
      co-funding by the anesthesia group in 35%. CONCLUSIONS: At least 61 or 44% of the
      140 US academic departments surveyed in this study have already implemented, are
      planning to acquire, or are currently searching for an AIMS. Adoption of AIMS
      technology appears to have reached sufficient momentum within academic
      anesthesiology departments to result in a fundamental change.

PMID- 18806049
TI  - The risk of severe postoperative pain: modification and validation of a clinical
      prediction rule.
AB  - BACKGROUND: Recently, a prediction rule was developed to preoperatively predict
      the risk of severe pain in the first postoperative hour in surgical inpatients.
      We aimed to modify the rule to enhance its use in both surgical inpatients and
      outpatients (ambulatory patients). Subsequently, we prospectively tested the
      modified rule in patients who underwent surgery later in time and in another
      hospital (external validation). METHODS: The rule was originally developed from
      the data of 1395 adult inpatients. We modified the rule with the data of 549
      outpatients who underwent surgery between 1997 and 1999 in the same center
      (Academic Medical Center Amsterdam, The Netherlands). Furthermore, we tested the
      performance of the modified rule in 1035 in- and outpatients who underwent
      surgery in 2004, in the University Medical Center Utrecht, The Netherlands
      (external validation). Performance was quantified by the rule's calibration
      (agreement between observed frequencies and predicted risks) and discrimination
      (ability to distinguish between patients at high and low risk). RESULTS:
      Modification of the original rule to enhance prediction in outpatients included
      reclassification of the predictor "type of surgery," addition of the predictor
      "surgical setting" (ambulatory surgery: yes/no) and addition of interaction terms
      between surgical setting and the other predictors. One-third of the patients in
      the Utrecht cohort reported severe postoperative pain (36%), compared to 62% of
      the patients in the Amsterdam cohort. The distribution of most predictors was
      similar in the two cohorts, although the patients in the Utrecht cohort were
      slightly older, more often underwent ambulatory surgery and had large expected
      incision sizes less often than patients in the Amsterdam cohort. The modified
      prediction rule showed good calibration, when an adjusted intercept was used for
      the lower incidence in the Utrecht cohort. The discrimination was reasonable
      (area under the Receiver Operating Characteristic curve 0.65 [95% confidence
      interval 0.57-0.73]). CONCLUSIONS: A previously developed prediction rule to
      predict severe postoperative pain was modified to allow use in both inpatients
      and outpatients. By validating the rule in patients who underwent surgery several
      years later in another hospital, it was shown that the rule could be generalized
      in time and place. We demonstrated that, instead of deriving new prediction rules
      for new populations, a simple adjustment may be enough to recalibrate prediction
      rules for new populations. This is in line with the perception that external
      validation and updating of prediction rules is a continuing and multistage
      process.

PMID- 18806050
TI  - The effect of dexmedetomidine on perioperative hemodynamics in patients
      undergoing craniotomy.
AB  - BACKGROUND: The perioperative course of patients undergoing intracranial surgery
      is frequently complicated by hypertensive episodes. Dexmedetomidine (DEX), an
      alpha-2 adrenoreceptor agonist, is gaining popularity in neuroanesthesia, because
      its sympatholytic and antinociceptive properties may improve hemodynamic
      stability at critical moments of surgery. We designed this study to assess the
      efficacy of DEX in controlling hypertensive responses in patients undergoing
      intracranial surgery. METHODS: Patients scheduled for elective craniotomy were
      randomly assigned to receive either sevoflurane-opioid or sevoflurane-opioid-DEX
      anesthesia. Bispectral index was used to maintain a similar level of hypnosis in
      both groups (40-50). Opioids, sevoflurane, and vasoactive medications were
      titrated in a routine manner, at the discretion of the blinded anesthesiologist
      managing the case, to maintain systolic blood pressure (SBP) targeted within 90
      130 mm Hg and heart rate (HR) between 50 and 90 bpm. Hemodynamic variables were
      continuously recorded and stored on a computer for analysis. Efficacy of the
      anesthetic technique in controlling SBP or HR is inversely proportional to the
      area under the curve (AUC) outside the targeted range. Areas under the curves
      above and below targeted ranges for SBP-time (AUCsbp mm Hg*min/h) and HR-time
      (bpm*min/h) were compared. Coefficient of variation was used to assess
      hemodynamic stability. RESULTS: Seventy-two patients were recruited for the
      study. Computerized records of 56 patients only were analyzed because of
      technical problems with data collection in 14 cases. AUCsbp for above the
      targeted range was significantly lower for patients in the DEX group (P=0.044).
      The coefficient of variation for SBP or HR did not differ between groups. A
      significantly smaller proportion of patients in the DEX group required treatment
      with antihypertensive medications (12 of 28, 42% vs 24 of 28, 86%, P=0.0008). The
      DEX group required fewer opioids in the intraoperative period, but there were no
      differences in the use of sevoflurane. In the postanesthesia care unit, patients
      in the DEX group had fewer hypertensive episodes (1.25+/-1.55 vs 2.50+/-2.00,
      P=0.0114) and were discharged earlier (91+/-17 vs 130+/-27 min, P<0.0001). There
      were no differences in the requirement for postoperative opioids or antiemetics.
      CONCLUSIONS: By using indices, which assess a global hemodynamic stability of the
      anesthetic, we determined that intraoperative DEX infusion was effective for
      blunting the increases in SBP perioperatively. The use of DEX did not increase
      the incidence of hypotension or bradycardia, common side effects of the drug.

PMID- 18806051
TI  - Planning for early emergence in neurosurgical patients: a randomized prospective
      trial of low-dose anesthetics.
AB  - BACKGROUND: For early detection of a cerebral complication, rapid awakening from
      anesthesia is essential after craniotomy. Systemic hypertension is a major
      drawback associated with fast tracking, which may predispose to formation of
      intracranial hematoma. Although various drugs have been widely evaluated, there
      are limited data with regards to use of anesthetics to blunt emergence
      hypertension. We hypothesized that use of low-dose anesthetics during craniotomy
      closure facilitates early emergence with a decrease in hemodynamic consequences.
      METHODS: Three emergent techniques were evaluated in 150 normotensive adult
      patients operated for supratentorial tumors under standard isoflurane anesthesia.
      At the time of dural closure, the patients were randomized to receive low-dose
      propofol (3 mg.kg(-1).h(-1)), fentanyl (1.5 microg.kg(-1).h(-1)) or isoflurane
      (end-tidal concentration of 0.2%) until the beginning of skin closure. Nitrous
      oxide was discontinued after head dressing. RESULTS: Median time to emergence was
      6 min with propofol, 4 min with fentanyl, and 5 min with isoflurane (P=0.008).
      More patients had hypertension in the pre-extubation compared with extubation or
      postextubation phase (P=0.009). Comparing the three groups, fewer patients
      required esmolol with fentanyl use overall, and in the pre-extubation phase
      (P=0.01). Significant midline shift in the preoperative cerebral imaging scans
      was found to be an independent risk factor for emergence hypertension.
      CONCLUSIONS: Pain during surgical closure may be an important cause of
      sympathetic stimulation leading to emergence hypertension. The use of low-doses
      of fentanyl during craniotomy closure is more advantageous than propofol or
      isoflurane for early emergence in neurosurgical patients and is the most
      effective technique for preventing early postoperative hypertension.

PMID- 18806052
TI  - Anemia and cerebral outcomes: many questions, fewer answers.
AB  - A number of clinical studies have associated acute anemia with cerebral injury in
      perioperative patients. Evidence of such injury has been observed near the
      currently accepted transfusion threshold (hemoglobin [Hb] concentration, 7-8
      g/dL), and well above the threshold for cerebral tissue hypoxia (Hb 3-4 g/dL).
      However, hypoxic and nonhypoxic mechanisms of anemia-induced cerebral injury have
      not been clearly elucidated. In addition, protective mechanisms which may
      minimize cerebral injury during acute anemia have not been well defined.
      Vasodilatory mechanisms, including nitric oxide (NO), may help to maintain
      cerebral oxygen delivery during anemia as all three NO synthase (NOS) isoforms
      (neuronal, endothelial, and inducible NOS) have been shown to be up-regulated in
      different experimental models of acute hemodilutional anemia. Recent experimental
      evidence has also demonstrated an increase in an important transcription factor,
      hypoxia inducible factor (HIF)-1alpha, in the cerebral cortex of anemic rodents
      at clinically relevant Hb concentrations (Hb 6-7 g/dL). This suggests that
      cerebral oxygen homeostasis may be in jeopardy during acute anemia. Under hypoxic
      conditions, cytoplasmic HIF-1alpha degradation is inhibited, thereby allowing it
      to accumulate, dimerize, and translocate into the nucleus to promote
      transcription of a number of hypoxic molecules. Many of these molecules,
      including erythropoietin, vascular endothelial growth factor, and inducible NOS
      have also been shown to be up-regulated in the anemic brain. In addition, HIF
      1alpha transcription can be increased by nonhypoxic mediators including cytokines
      and vascular hormones. Furthermore, NOS-derived NO may also stabilize HIF-1alpha
      in the absence of tissue hypoxia. Thus, during anemia, HIF-1alpha has the
      potential to regulate cerebral cellular responses under both hypoxic and normoxic
      conditions. Experimental studies have demonstrated that HIF-1alpha may have
      either neuroprotective or neurotoxic capacity depending on the cell type in which
      it is up-regulated. In the current review, we characterize these cellular
      processes to promote a clearer understanding of anemia-induced cerebral injury
      and protection. Potential mechanisms of anemia-induced injury include cerebral
      emboli, tissue hypoxia, inflammation, reactive oxygen species generation, and
      excitotoxicity. Potential mechanisms of cerebral protection include NOS/NO
      dependent optimization of cerebral oxygen delivery and cytoprotective mechanisms
      including HIF-1alpha, erythropoietin, and vascular endothelial growth factor. The
      overall balance of these activated cellular mechanisms may dictate whether or not
      their up-regulation leads to cytoprotection or cellular injury during anemia. A
      clearer understanding of these mechanisms may help us target therapies that will
      minimize anemia-induced cerebral injury in perioperative patients.

PMID- 18806053
TI  - Gaston Labat's Regional Anesthesia: the missing years.
AB  - Gaston Labat's textbook Regional Anesthesia: Its Technique and Clinical
      Application was one of the earliest regional anesthesia texts, and certainly one
      of the most successful. Although Dr. Labat was working on a third edition at the
      time of his death, its fate and the reason for a more than 30-year delay in
      publishing a third edition have often been speculated upon. A search of the John
      S. Lundy Archive revealed communications between Dr. Lundy and Labat's widow
      which help explain the delay. Further searches into the collections of John
      Adriani, MD, help explain how he came to be the one to publish the long-awaited
      third edition.

PMID- 18806054
TI  - Profound pain reduction after induction of memantine treatment in two patients
      with severe phantom limb pain.
AB  - We present the cases of two patients who suffered severe lower extremity injuries
      and subsequently developed phantom limb pain (PLP) that was refractory to high
      dose opioids and adjunctive pain medications. Both patients were receiving large
      doses of oral methadone, IV hydromorphone via a patient-controlled analgesia
      delivery system, and adjunctive medications including tricyclic antidepressants,
      nonsteroidal anti-inflammatory medications, and anti-epileptics. Despite these
      treatments, the patients had severe PLP. Upon induction of the oral N-methyl-D
      aspartate receptor antagonist memantine, both patients had a profound reduction
      in their PLP without any apparent side effects from the medication.

PMID- 18806055
TI  - Ultra-low dose ketamine and memantine treatment for pain in an opioid-tolerant
      oncology patient.
AB  - Patients taking high-dose opioids chronically for tumor-related or neuropathic
      pain may develop pain that is refractory to opioids. One option for control of
      such pain is the use of the N-methyl-D-aspartate (NMDA) receptor antagonist
      ketamine. We describe a case of opioid-refractory pain that responded to a low
      dose IV infusion of ketamine in the inpatient setting. The patient was then
      successfully transitioned to oral memantine for long-term outpatient management,
      in a novel use of this oral NMDA receptor antagonist. We present recent findings
      from basic research on pain mechanisms to explain why opioid tolerance, as in
      this patient, may contribute to the analgesic benefit of NMDA receptor
      antagonists.

PMID- 18806056
TI  - The side effects of morphine and hydromorphone patient-controlled analgesia.
AB  - BACKGROUND: Despite "clinical lore" among health care providers that treatment
      with hydromorphone results in improved pain control and fewer adverse side
      effects, morphine continues to be the first-line medication for postoperative
      patient-controlled analgesia (PCA). In this study, we compared the efficacy and
      side-effect profiles of morphine and hydromorphone at concentrations producing
      equivalent drug effect measured by pain score and miosis. METHODS: We conducted a
      prospective, randomized, double-blind trial of 50 general and gynecological
      surgery patients. Subjects were randomly assigned to receive either morphine (1
      mg/mL) or hydromorphone (0.2 mg/mL) via PCA after surgery and were followed for a
      period of 8 h. The primary outcome was nausea. Secondary outcome variables were
      pruritus, vomiting, sedation, pain report, pupillary miosis, and patient
      satisfaction. RESULTS: The side effect profile was not different between drugs.
      The incidence of nausea did not differ between morphine and hydromorphone-treated
      patients (1 h: 44% vs 52%, 8 h: 68% vs 64%), vomiting (1 h: 4% vs 0%, 8 h: 0% vs
      4%), or pruritus (1 h: 4% vs 16%, 8 h: 40% vs 40%). There was no difference in
      the amount of medication required to treat side effects or patient satisfaction.
      The average ratio of morphine to hydromorphone use was about 7:1. The patients
      used 10.9+/-6.0 mg morphine versus 1.57+/-1.0 mg hydromorphone after 1 h and
      29.0+/-18.0 mg morphine versus 3.9+/-2.5 mg hydromorphone after 8 h. There was no
      difference between the morphine and hydromorphone groups with respect to
      postoperative pain scores with movement at 1 h (7.9+/-2.3 vs 7.1+/-2.4) or 8 h
      (5.7+/-2.8 vs 5.9+/-2.7). There was also no difference in pain at rest or miosis
      between groups. CONCLUSIONS: We found no systematic difference between morphine
      and hydromorphone in opioid-related side effects. Neither was there any
      difference in efficacy of pain control or patient satisfaction when patients self
      titrated to equal drug effect as measured by equianalgesia and pupillary miosis.
      The choice between morphine and hydromorphone for use in PCA should be guided by
      patient history, as there may be idiosyncratic reactions to either drug.

PMID- 18806057
TI  - Ultrasonography reinvents the originally described technique for ganglion impar
      neurolysis in perianal cancer pain.
AB  - Visceral pain in the perineal area associated with malignancies may be
      effectively treated with neurolysis of the ganglion impar. Since the first
      description of the technique of accessing the ganglion impar through anococcygeal
      ligament, many techniques for ganglion impar block have been described. We
      present a patient diagnosed with carcinoma of the anal canal who was successfully
      given ultrasound-guided ganglion impar block using a Chiba needle inserted
      through the anococcygeal ligament. In summary, ultrasound-guided ganglion impar
      neurolysis is a fast, safe, and cost-effective method, which can be used as a
      first-line pain relief intervention for good quality of life in patients with
      perianal cancers.

PMID- 18806058
TI  - Perioperative management of patients with an intrathecal drug delivery system for
      chronic pain.
AB  - The use of intrathecal medications in the treatment of chronic pain is becoming
      more commonplace. As such, the incidence of encountering patients receiving
      therapy via an intrathecal drug delivery system in the perioperative period will
      also increase. In this case series, we discuss anesthetic management and
      postoperative analgesic issues in three patients with indwelling intrathecal drug
      delivery systems placed for treatment of chronic pain.

PMID- 18806059
TI  - Use of bulleyaconitine A as an adjuvant for prolonged cutaneous analgesia in the
      rat.
AB  - BACKGROUND: Bulleyaconitine A (BLA) is an analgesic and antiinflammatory drug
      isolated from Aconitum plants. BLA has several potential targets, including
      voltage-gated Na+ channels. We tested whether BLA elicited long-lasting cutaneous
      analgesia, when co-injected with lidocaine and epinephrine, as a model for
      prolonged infiltration anesthesia. METHODS: The local anesthetic properties of
      BLA were assessed by the patch-clamp technique in HEK293t cells expressing Nav1.7
      and Nav1.8 neuronal Na+ channels, both crucial for nociception. Drug solutions
      (0.6 mL) were injected subcutaneously via rat shaved dorsal skin. Inhibition of
      the cutaneous trunci muscle reflex was evaluated by pinpricks. Skin cross
      sections were stained with hematoxylin and eosin or with antibodies against
      PGP9.5. RESULTS: BLA at 10 microM interacted minimally with resting or
      inactivated Nav1.7 and Nav1.8 Na+ channels when infrequently stimulated to +50 mV
      for 3 ms. However, when stimulated at 2 Hz for 1000 pulses, their peak Na+
      currents were >90% reduced by BLA. This use-dependent inhibition was not
      significantly reversed after 15-min washing. Complete nociceptive blockade after
      injection of lidocaine (0.5%)/epinephrine (1:200,000) lasted for approximately 1
      h in rats; full recovery occurred after approximately 6 h. Co-injection of 0.125
      mM BLA with lidocaine/epinephrine increased the duration of complete nociceptive
      blockade to 24 h. Full recovery occurred after approximately 6 days. Skin
      histology including peripheral nerve fibers appeared unaffected by BLA.
      CONCLUSIONS: BLA inhibits Nav1.7 and Nav1.8 Na+ currents in a use-dependent
      manner. Co-injection of BLA at <or=0.125 mM with lidocaine and epinephrine
      elicits complete cutaneous analgesia that lasts for up to 24 h without adverse
      effects.

PMID- 18806060
TI  - Percutaneous pulsed radiofrequency reduces mechanical allodynia in a neuropathic
      pain model.
AB  - BACKGROUND: Neuropathic pain is a result of a primary lesion or dysfunction of
      the peripheral or central nervous system, and its treatment is challenging.
      Animal models have been helpful in understanding mechanisms of neuropathic pain
      and in developing new treatment strategies. In this study, we examined the effect
      of percutaneous pulsed radiofrequency (PRF), which is a minimally invasive pain
      treatment method, on mechanical allodynia in a neuropathic pain rat model.
      METHODS: Neuropathic pain was achieved in a peripheral nerve pain model by
      performing L5-6 spinal nerve ligation. On the 14th postoperative day,
      percutaneous PRF was applied to the plantar side of the left rear paw. Animals
      were evaluated for mechanical allodynia with both dynamic plantar aesthesiometer
      (DPA) (weight and paw withdrawal time) and von Frey filaments (VF) on the 14th
      postoperative day and 1, 3, 5, 7, 10, and 14 days after PRF treatment.
      Experiments were conducted in six groups: Sham-operated+placebo PRF 6 min, sham
      operated+PRF 6 min, neuropathic (NP)+2 min placebo PRF, NP+2 min PRF, NP+6 min
      placebo PRF, and NP+6 min PRF. RESULTS: Allodynia developed in all animals in the
      NP groups compared to sham-operated animals (P=0.0001). DPA and VF showed that
      PRF application for 2 min significantly improved allodynia on 1-14th post-PRF
      day, compared to placebo PRF (P=0.0001). Although DPA (both weight and paw
      withdrawal time) did not show any therapeutic effect from 6 min PRF application
      on 1-14th post-PRF days (P=1.00), VF demonstrated transient improvement for the
      first week, which disappeared on later evaluations of the 6 min PRF group.
      CONCLUSIONS: Percutaneous PRF is an effective treatment option in the NP pain
      model, and further studies are needed to clarify its underlying mechanisms of
      action.

PMID- 18806061
TI  - Infusate contamination in regional anesthesia: what every anesthesiologist should
      know.
AB  - Infection can be a devastating complication of regional anesthesia. Contaminated
      infusate as a cause of infection in neuraxial anesthesia or peripheral nerve
      blockade has rarely been reported in the literature. However, it may be an
      important source of morbidity, especially as increasing numbers of patients are
      being discharged with perineural catheters and portable pumps of local
      anesthetic, which may infuse for several days at home. Two important issues
      related to infusate contamination in regional anesthesia are that of "hang-time"
      and sterile compounding practices. Hang-time can be defined as the maximum length
      of time during which an admixture preparation (infusate) can be safely
      administered without risk of microbiological or chemical instability. In the
      United States, there are currently no national guidelines on the hang-times of
      regional anesthesia infusates. On the other hand, guidelines for the sterile
      compounding of infusions used in regional anesthesia are now established by
      United States Pharmacopeia and The National Formulary Chapter 797, entitled
      "Pharmaceutical Compounding, Sterile Preparations." These guidelines have
      significant implications for the anesthesiologist. In this review, we examined
      the available literature regarding contaminated infusate as a cause of infection
      in regional anesthesia, to discuss strategies for the prevention of such
      contamination including the appropriate hang-time for infusates, and to discuss
      the implications of United States Pharmacopeia and The National Formulary Chapter
      797 for anesthesiologists.

PMID- 18806062
TI  - Acute neck cellulitis and mediastinitis complicating a continuous interscalene
      block.
AB  - We report a case of acute neck cellulitis and mediastinitis complicating a
      continuous interscalene brachial plexus block. A 61-yr-old man was scheduled for
      an elective arthroscopic right shoulder rotator cuff repair. A continuous
      interscalene block was done preoperatively and 20 mL of 0.5% bupivacaine and 20
      mL of 2% mepivacaine were injected through the catheter. Postoperative analgesia
      was provided by a continuous infusion of bupivacaine, 0.25% at 5 mL/h for 39 h
      using a 240-mL elastomeric disposable pump. The day after surgery, the patient
      complained of neck pain. The analgesic block was not fully effective. He was
      discharged home. Three days later, the patient was readmitted with neck edema and
      erythema, fever and fatigue. Neck ultrasonography and computed tomographic scan
      revealed an abscess of the interscalene and sternocleidomastiod muscles and
      cellulitis, as well as acute mediastinitis. Two blood cultures and surgical
      samples were positive for Staphylococcus aureus. The infection was treated with
      surgery, the site was surgically debrided, and a 2-mo course of vancomycin,
      imipenem, and oxacilline. The technique of drawing local anesthetic from the
      bottle and filling the elastomeric pump was the most likely cause of infection.
      This case emphasizes the importance of strict aseptic conditions during puncture,
      catheter insertion, and management of the local anesthetic infusate.

PMID- 18806063
TI  - Melatonin improves tourniquet tolerance and enhances postoperative analgesia in
      patients receiving intravenous regional anesthesia.
AB  - BACKGROUND: Melatonin has anxiolytic and potential analgesic effects. We assessed
      the efficacy of melatonin premedication in reducing tourniquet-related pain and
      improving analgesia in patients receiving IV regional anesthesia (IVRA). METHODS:
      Forty patients undergoing elective hand surgery under IVRA were randomly assigned
      into two groups (20 patients each) to receive either melatonin 10 mg (melatonin
      group) or placebo (control group) as oral premedication. IVRA was achieved with
      lidocaine, 3 mg/kg, diluted with saline to a total volume of 40 mL. Anxiety
      scores, hemodynamic changes, sensory and motor block onset and recovery times,
      tourniquet pain, the quality of intraoperative anesthesia, time to first
      analgesic request, and 24 h analgesic requirements were recorded. RESULTS: After
      premedication, the anxiety scores were significantly reduced in the melatonin
      group (P=0.023). During surgery, patients who received melatonin premedication
      had better tourniquet tolerance (lower verbal pain scores at 30, 40, and 50 min
      after tourniquet inflation, P<0.05), lower rescue fentanyl requirements (15.6+/
      21.9 vs 45.7+/-33.4 microg, P=0.002), longer time to the first postoperative
      analgesic request (145.4+/-20.2 min vs 74.6+/-12.8, P<0.001) and lower
      postoperative diclofenac consumption at 24 h (86.3+/-27.5 mg vs 116.3+/-38.3 mg,
      P=0.007) compared with the control group. CONCLUSIONS: Melatonin is an effective
      premedication before IVRA since it reduced patient anxiety, decreased tourniquet
      related pain, and improved perioperative analgesia.

PMID- 18806064
TI  - The effect of injectate conductivity on the electric field with the nerve
      stimulator needle: a computer simulation.
AB  - BACKGROUND: Electrical neural stimulation is commonly used to localize neural
      structures and place local anesthetic for regional anesthesia. The sharp tip of
      the stimulating needle gives rise to an electric field which is highly localized.
      The electrostatic effect of the injected solution on the field distribution and
      strength has not previously been modeled. METHODS: The three-dimensional electric
      field around a 0.7 mm diameter, un-insulated, hollow needle with a 30 degrees
      bevel was calculated in silico using a hybrid finite difference/impedance network
      method to solve the Laplace equation. The surrounding tissue was assumed to be
      electrically uniform. A sphere of injectate centered on the bevel was modeled as
      a region of conductivity differing from that of the bulk tissue. RESULTS: The
      electric field strength was highly concentrated at the needle tip and decayed
      rapidly with distance r approximately as 1/r1.7. It was demonstrated that the
      electric field in the immediate vicinity of the needle tip was greatly reduced in
      the presence of solutions with conductivity greater than that of the surrounding
      tissue. A 1.5 mm radius region of conducting solution (equivalent to saline or
      local anesthetics) reduced the field by 31%. The same volume of a relatively
      insulating injectate, such as dextrose solution, led to a field enhancement of
      approximately 15%. CONCLUSIONS: The electric field magnitude in the vicinity of
      the needle tip decayed more slowly with distance than predicted by Coulomb's law.
      This was independent of the presence of injectate. The near instantaneous
      abolition of muscle twitch with injection of small volumes of local anesthetic is
      consistent with an electrostatic effect, rather than a pharmacological or
      mechanical one. The change in field strength depended upon the volume of the
      injectate and its conductivity relative to that of the surrounding tissue. In
      this simulation, even tiny volumes of injectate lead to significant changes in
      field and therefore threshold current, which may have clinical implications.

PMID- 18806065
TI  - A "new" automated bolus technique for continuous popliteal block: a prospective,
      randomized comparison with a continuous infusion technique.
AB  - BACKGROUND: We designed the present, prospective, randomized, double-blind study
      to compare the administration of an automated intermittent bolus dose with a
      conventional technique of continuous infusion of local anesthetic for
      postoperative analgesia in continuous popliteal sciatic nerve blockade. METHODS:
      Forty-four patients undergoing hallux valgus repair were randomly assigned to
      receive either a continuous infusion of 0.125% levobupivacaine with an infusion
      rate of 5 mL/h (continuous infusion group, n=22) or automated bolus doses of 5 mL
      every hour of the same local anesthetic (automated bolus group, n=22) for 24 h.
      Postoperative pain scores were assessed using a verbal rating pain score. The
      amount of rescue tramadol medication for pain was also recorded. RESULTS: In
      patients of the automated bolus group there was a reduction in pain scores
      (P<0.05) during the postoperative period, when compared to patients of the
      continuous infusion group. Five patients in the automated bolus group (24%) and
      11 patients of the continuous group (52%) required rescue tramadol analgesia
      (P=0.055). CONCLUSION: The present investigation demonstrated that local
      anesthetic administered by an automated bolus technique provided better
      postoperative pain relief than a continuous infusion technique for continuous
      popliteal nerve block after foot surgery.

PMID- 18806066
TI  - Urethral injury during potassium-titanyl-phosphate laser prostatectomy
      complicated by transurethral resection syndrome.
AB  - The green light potassium-titanyl-phosphate laser photoselective vaporization of
      the prostate is the latest modality for treatment of benign prostatic
      obstruction. Because of effective superficial tissue coagulation, intravascular
      absorption of fluid is minimal; therefore, development of transurethral resection
      syndrome is unlikely. To our knowledge, this is the first report of a patient
      undergoing photoselective vaporization of the prostate who developed full-blown
      transurethral resection syndrome because of intravascular absorption of sterile
      water. Absorption of hypotonic irrigant presumably occurred through the injury
      induced during insertion of the laser cystoscope.

PMID- 18806067
TI  - Skin testing performed in individuals cannot be compared with responses from
      anaphylactic patients.

PMID- 18806068
TI  - Preoperative coronary revascularization in high-risk patients undergoing vascular
      surgery.

PMID- 18806069
TI  - A method to improve use of a preformed nasal tube for fiberoptic nasal
      intubation.

PMID- 18806070
TI  - Does preoperative level of antithrombin III predict heparin resistance during
      extracorporeal circulation?

PMID- 18806071
TI  - A fluoroscopic diagnosis of bronchus suis or porcine bronchus to explain
      hypoxemia during anesthesia.

PMID- 18806072
TI  - Plastic bronchitis in a child with Fontan's physiology presenting for urgent
      rigid bronchoscopy.

PMID- 18806074
TI  - Debt control for young DO's.

PMID- 18806073
TI  - Airway management in neonates with occipital encephalocele: easy does it.

PMID- 18806075
TI  - Osteopathic manipulation: promise for infantile colic.

PMID- 18806076
TI  - One hundred thousand cases of influenza with a death rate of one-fortieth of that
      officially reported under conventional medical treatment.

PMID- 18806077
TI  - Statins and sepsis: good bullet, disappearing target.
AB  - Despite several decades of research and phenomenal advances in technology and
      therapeutics, sepsis remains a catastrophic enigma. As a frequent cause of death,
      sepsis now rivals acute myocardial infarction. The longstanding therapeutic
      principles of early antibiotics use and supportive care have been difficult to
      improve upon. The authors conducted a concise review of pertinent literature on
      the pathophysiologic mechanisms of sepsis and the pharmacologic effects of
      statins. They conclude that, though statins possess anti-inflammatory and lipid
      lowering properties, these effects may not be advantageous throughout the
      changing immunoresponse that can occur in sepsis syndrome. Based on the available
      information, statin therapy seems advantageous before the onset of sepsis and
      during sepsis resolution--but not during the compensatory anti-inflammatory
      response that may occur. Thus, the authors recommend that, until the status of a
      patient's changing immune response can be clearly determined, the uninterrupted
      use of statin therapy throughout the full spectrum of sepsis should be avoided.

PMID- 18806078
TI  - Intraobserver reliability of cranial strain patterns as evaluated by osteopathic
      physicians: a pilot study.
AB  - CONTEXT: Few studies of inter- or intraobserver reliability have focused on
      evaluations of cranial strain patterns. OBJECTIVE: To determine whether
      substantial intraobserver reliability can be achieved by osteopathic physicians
      (DOs) using common palpatory tests to diagnose cranial dysfunction. METHODS:
      Forty-eight subjects were divided into three diagnostic groups, categorized as
      those with asthma, headaches, or neither asthma nor headaches (ie, healthy
      control group). Two blinded DO examiners separately evaluated approximately 8
      subjects from each group (4 subjects per session), conducting diagnostic tests
      for cranial rhythmic impulse (CRI) rate, cranial strain patterns, and quadrants
      of restriction. RESULTS: Overall, among the three diagnostic procedures, cranial
      strain patterns showed the highest intraobserver reliability (kappa=0.67). The
      highest intraobserver reliability was achieved in cranial strain patterns for the
      control group (kappa=0.82), followed by the headache (kappa=0.67) and asthma
      (kappa=0.52) groups. Diagnoses of the left anterior quadrant of restriction also
      showed substantial intraobserver reliability for the headache and control groups
      (kappa=0.60 and 0.61, respectively). Diagnoses of three quadrants of restriction
      showed moderate overall intraobserver reliability (kappa=0.44-0.52), while the
      left posterior quadrant had only fair overall intraobserver reliability
      (kappa=0.33). CONCLUSION: Osteopathic physicians can obtain substantial
      intraobserver reliability when diagnosing cranial strain patterns in healthy
      subjects as well as those with asthma or headache. However, results are less
      promising for diagnoses of CRI and quadrants of restriction.

PMID- 18806079
TI  - Postpartum thyroid measures and depressive symptomology: a pilot study.
AB  - CONTEXT: While correlations have been demonstrated between postpartum depression
      and psychosocial and circumstantial risk factors, some evidence exists for a
      similar relationship between postpartum depression and thyroid measures.
      OBJECTIVE: To search at 4 weeks postpartum for correlations of numerical scores
      on a postnatal depression screening tool and thyroid measures. METHODS: Subjects
      took the Edinburgh Postnatal Depression Scale (EPDS) prenatally and at 4 weeks
      postpartum. Participants were also given blood tests for thyroid-stimulating
      hormone (TSH), free thyroxine4, thyroid peroxidase, and thyroglobulin at the same
      testing intervals. RESULTS: Fifty-one subjects aged 18 years or older were
      recruited. Subjects with higher serum TSH at 4 weeks postpartum tended to have
      higher EPDS scores. Similarly, the 7 subjects (13.7%) with positive postnatal
      thyroid antibody tests were more likely than their counterparts to have higher
      EPDS scores. CONCLUSIONS: Presence of thyroid autoantibodies or higher TSH levels
      during the postpartum period may be related to depressive symptoms or dysphoric
      mood, even when clinical depression is not present. Either or both of these
      associations may contribute, along with other physiologic and psychosocial risk
      factors, to postpartum depression. (ClinicalTrials.gov number NCT00565032).

PMID- 18806080
TI  - Clinical and research protocol for osteopathic manipulative treatment of elderly
      patients with pneumonia.
AB  - Pneumonia in elderly patients is a major public health concern because of greater
      morbidity and mortality and longer hospital stays relative to younger
      populations. Based on the premise that osteopathic manipulative treatment (OMT)
      is beneficial in the management of pulmonary infections, the Multicenter
      Osteopathic Pneumonia Study in the Elderly (MOPSE) was designed as a prospective
      randomized controlled trial to evaluate the efficacy of OMT as an adjunct to the
      current pharmacologic treatment of elderly patients hospitalized for pneumonia.
      The protocol developed for MOPSE has its origins in early osteopathic medical
      literature at a time when effective antibiotic therapy was unavailable and
      osteopathic physicians relied on physical examination and empiric reasoning to
      develop treatment strategies and OMT techniques to improve host defenses against
      pneumonia. The present paper reviews the early osteopathic medical literature to
      identify the reasoning behind the OMT techniques that are the basis for the
      design of the MOPSE protocol. Likewise, the contemporary medical literature
      relevant to the protocol is reviewed. Finally, a description of the study design
      and the OMT and light touch (sham) protocols used in MOPSE are provided.

PMID- 18806081
TI  - Type 2 diabetes mellitus in childhood: obesity and insulin resistance.
AB  - As rates of childhood obesity climb, type 2 diabetes mellitus has increasingly
      been diagnosed in children and adolescents, with the highest incidence occurring
      among youth from racial and ethnic minority backgrounds. The serious
      complications associated with type 2 diabetes mellitus make it essential for
      physicians to be aware of risk factors and screening guidelines, allowing for
      earlier patient diagnosis and treatment. It is also important for physicians to
      be aware of the treatment options available, including weight control through
      diet and exercise as well as common pharmacotherapeutic options.

PMID- 18806082
TI  - Incidental pleural-based pulmonary lymphangioma.
AB  - Adult benign thoracic lymphangiomas typically present as incidental mediastinal
      lesions, or, more rarely, as solitary pulmonary nodules. Symptomatic compression
      of vital structures may require lesion resection or sclerotherapy. In the present
      report, we describe the incidental finding of a solitary pleural-based pulmonary
      lymphangioma in a 38-year-old woman with chronic arm and shoulder pain. Positron
      emission tomography revealed that the lesion was highly fluorodeoxyglucose-avid.
      Biopsy exposed benign tissue consistent with lymphangioma. After continued
      radiographic tests, the lesion was determined to be an unlikely source of the
      patient's chronic pain. The present report is, to our knowledge, the first
      published case of solitary pleural-based pulmonary lymphangioma in the medical
      literature.

PMID- 18806085
TI  - Osteopathic certification evolving into a continuous certification model.

PMID- 18806089
TI  - Vitamin a deficiency and clinical disease: an historical overview.
AB  - Vitamin A deficiency has a plethora of clinical manifestations, ranging from
      xerophthalmia (practically pathognomonic) to disturbances in growth and
      susceptibility to severe infection (far more protean). Like other classical
      vitamin deficiency states (scurvy, rickets), some of the signs and symptoms of
      xerophthalmia were recognized long ago. Reports related to vitamin A and/or
      manifestations of deficiency might conveniently be divided into "ancient"
      accounts; eighteenth to nineteenth century clinical descriptions (and their
      purported etiologic associations); early twentieth century laboratory animal
      experiments and clinical and epidemiologic observations that identified the
      existence of this unique nutrient and manifestations of its deficiency; and, most
      recently, a flowering of carefully conducted clinical studies and field-based
      randomized trials that documented the full extent and impact of deficiency among
      the poor of low- and middle-income countries, which in turn changed global health
      policy.

PMID- 18806090
TI  - Polyamine metabolism and transforming growth factor-beta signaling are affected
      in Caco-2 cells by differentially cooked broccoli extracts.
AB  - The health benefits of consuming cruciferous vegetables are widely considered to
      be due to the biological activity of glucosinolate degradation products. However,
      it is conceivable that other phytochemicals within crucifers may also have
      biological activity that may contribute to health benefits. In this study, we
      analyzed global gene expression in Caco-2 cells exposed to extracts derived from
      broccoli that had been heat treated to different extents to result in contrasting
      profiles of glucosinolates and their degradation products. Extracts microwaved
      for 0, 1, and 4 min contained 9.5, 25.5, and 0 micromol/L sulforaphane and
      induced changes in expression of 381, 1017, and 101 genes, respectively (>2 fold;
      P < 0.01). Seventy-two genes showed similar changes in expression after treatment
      with all 3 extracts. These included genes involved in polyamine catabolism and
      transforming growth factor (TGF)-beta signaling. Consistent with these changes in
      gene expression, subsequent studies demonstrated that exposing cells to these
      extracts, including the 4-min extract that contained no glucosinolate degradation
      products, increased putrescine and N-acetyl-spermine concentration, and
      suppressed the TGFbeta1-mediated induction of phosphorylated Smad 2. This is the
      first report, to our knowledge, of phytochemicals from a cruciferous vegetable
      affecting both a signaling pathway and a catabolic process.

PMID- 18806091
TI  - Chromium (D-phenylalanine)3 supplementation alters glucose disposal, insulin
      signaling, and glucose transporter-4 membrane translocation in insulin-resistant
      mice.
AB  - Chromium has gained popularity as a nutritional supplement for diabetic and
      insulin-resistant subjects. This study was designed to evaluate the effect of
      chronic administration of a novel chromium complex of d-phenylalanine [Cr(D
      phe)(3)] in insulin-resistant, sucrose-fed mice. Whole-body insulin resistance
      was generated in FVB mice by 9 wk of sucrose feeding, following which they were
      randomly assigned to be unsupplemented (S group) or to receive oral Cr(D-phe)(3)
      in drinking water (SCr group) at a dose of 45 mug.kg(-1).d(-1) ( approximately
      3.8 mug of elemental chromium.kg(-1).d(-1)). A control group (C) did not consume
      sucrose and was not supplemented. Sucrose-fed mice had an elevated serum insulin
      concentration compared with controls and this was significantly lower in sucrose
      fed mice that received Cr(D-phe)(3), which did not differ from controls. Impaired
      glucose tolerance in sucrose-fed mice, evidenced by the poor glucose disposal
      rate following an intraperitoneal glucose tolerance test, was significantly
      improved in mice receiving Cr(D-phe)(3). Chromium supplementation significantly
      enhanced insulin-stimulated Akt phosphorylation and membrane-associated glucose
      transporter-4 in skeletal muscles of sucrose-fed mice. In cultured adipocytes
      rendered insulin resistant by chronic exposure to high concentrations of glucose
      and insulin, Cr(D-phe)(3) augmented Akt phosphorylation and glucose uptake. These
      results indicate that dietary supplementation with Cr(D-phe)(3) may have
      potential beneficial effects in insulin-resistant, prediabetic conditions.

PMID- 18806092
TI  - Perilipin polymorphism interacts with dietary carbohydrates to modulate
      anthropometric traits in hispanics of Caribbean origin.
AB  - Perilipin (PLIN) is the major protein surrounding lipid droplets in adipocytes
      and regulates adipocyte metabolism by modulating the interaction between lipases
      and triacylglycerol stores. Associations between PLIN gene polymorphisms and
      obesity risk have been described, but interactions with dietary macronutrients
      require further attention. We examined whether dietary macronutrients (e.g.
      carbohydrates and fats) modulated the associations of the common PLIN 11482G > A
      (rs894160) single nucleotide polymorphism with obesity. We studied a population
      based sample of Caribbean-origin Hispanics (n = 920, aged 45-74 y) living in the
      Boston area. Obesity measures (waist and hip circumference, BMI) did not differ
      between GG subjects and carriers of the A allele (GA and AA). In multivariate
      linear regression models, we found a significant interaction between complex
      carbohydrate intake as a continuous variable and PLIN 11482 G > A genotype for
      waist circumference (P = 0.002). By dichotomizing complex carbohydrate intake, we
      found significantly different effects across PLIN 11482G > A genotypes. When
      complex carbohydrate intake was <144 g/d, waist circumference was larger in PLIN
      11482G > A carriers (P = 0.024). Conversely, when complex carbohydrate intake was
      >/=144 g/d, waist and hip circumferences were less in PLIN 11482G > A carriers (P
      < 0.05). These interactions were not found for simple sugars or total
      carbohydrates. We identified a significant gene-diet interaction associated with
      obesity at the PLIN locus. In subjects with higher complex carbohydrate intake,
      the minor allele was protective against obesity, whereas in subjects with lower
      carbohydrate intake, the minor allele was associated with increased obesity.
      These interactions may be relevant to dietary management of obesity.

PMID- 18806093
TI  - Liver fatty acid-binding protein gene-ablated female mice exhibit increased age
      dependent obesity.
AB  - Previous work conducted in our laboratory suggested a role for liver fatty acid
      binding protein (L-FABP) in obesity that develops in aging female L-FABP gene
      ablated (-/-) mice. To examine this possibility in more detail, cohorts of wild
      type (+/+) and L-FABP (-/-) female mice were fed a standard, low-fat, nonpurified
      rodent diet for up to 18 mo. Various obesity-related parameters were examined,
      including body weight and fat and lean tissue mass. Obesity in (-/-) mice was
      associated with increased expression of nuclear receptors that induce PPARalpha
      (e.g. hepatocyte nuclear factor 1alpha, genotype effect) and of PPARalpha
      regulated proteins involved in uptake of free (lipoprotein lipase and fatty acid
      transport protein, genotype, and/or age effect) and esterified (scavenger
      receptor class B type 1, genotype effect) long-chain fatty acids (LCFA). Hepatic
      total lipid and neutral lipid levels were not affected by age or genotype,
      consistent with absence of gross and histologic steatosis. There was increased
      mRNA expression of liver proteins involved in LCFA oxidation [mitochondrial 3
      oxoacyl-CoA thiolase (genotype effect) and butyryl-CoA dehydrogenase (genotype
      and/or age effect)], increased expression of LCFA esterification enzymes
      [glycerol-3-phosphate acyltransferase (age x genotype effect) and acyl
      CoA:cholesterol acyltransferase-2 (genotype and/or age effect)], and increased
      expression of proteins involved in intracellular transfer and secretion of
      esterified LCFA [liver microsomal triacylglycerol transfer protein (genotype
      effect), serum apolipoprotein (apo) B (genotype or age effect), and liver apoB
      (age and age x genotype effect)]. The data support a working model in which
      obesity development in these mice results from shifts toward reduced energy
      expenditure and/or more efficient energy uptake in the gut.

PMID- 18806094
TI  - Increased apoptosis in high-fat diet-induced nonalcoholic steatohepatitis in rats
      is associated with c-Jun NH2-terminal kinase activation and elevated proapoptotic
      Bax.
AB  - Hepatocyte apoptosis in addition to oxidative stress could be a key component in
      the pathogenesis of nonalcoholic steatohepatitis (NASH). However, the underlying
      mechanisms of hepatocellular apoptotic response associated with oxidative stress
      have not been investigated in high-fat diet (HFD)-induced NASH models. In this
      study, Sprague-Dawley rats were fed either a Lieber-DeCarli control diet (CD; 35%
      energy from fat) or a HFD (71% energy from fat) for 6 wk. Pathologic lesions,
      lipid peroxidation products, and apoptotic hepatocytes in the liver were
      examined. The expressions of hepatic tumor necrosis factor-alpha (TNFalpha) and
      protein concentrations of cleaved caspase-3, cytochrome p4502E1 (CYP2E1),
      phosphorylated c-Jun NH(2)-terminal kinase (JNK), Bax, Bcl-2, and Bcl-xl were
      measured. Results showed that the key histological features of NASH, including
      steatosis, inflammatory cell infiltration, and ballooning degeneration of
      hepatocytes, were induced by HFD feeding, with increased hepatic TNFalpha mRNA
      expression. HFD-fed rats had elevated lipid peroxidation products and CYP2E1
      protein in the liver. The apoptotic hepatocytes were significantly greater in
      livers of rats fed HFD than in those fed CD, and these were associated with a
      higher level of cleaved caspase-3. In addition, HFD feeding increased both
      hepatic phosphorylated JNK and pro-apoptotic Bax but did not affect anti
      apoptotic Bcl-2 and Bcl-xl compared with CD feeding. These data indicate that the
      increased oxidative stress and its associated JNK activation as well as an
      imbalance of pro- and anti-apoptotic proteins in the Bcl-2 family all contribute
      to high hepatocyte apoptosis that may play an important role in the pathogenesis
      of NASH in this model.

PMID- 18806095
TI  - N-acetylcysteine attenuates progression of liver pathology in a rat model of
      nonalcoholic steatohepatitis.
AB  - A "2-hit" model for nonalcoholic steatohepatitis (NASH) has been proposed in
      which steatosis constitutes the "first hit" and sensitizes the liver to potential
      "second hits" resulting in NASH. Oxidative stress is considered a candidate for
      the second hit. N-acetylcysteine (NAC), an antioxidant, has been suggested as a
      dietary therapy for NASH. We examined the effects of NAC in a rat total enteral
      nutrition (TEN) model where NASH develops as the result of overfeeding dietary
      polyunsaturated fat. Male Sprague-Dawley rats consumed pelleted AIN-93G diets ad
      libitum or were overfed a 9200 kJ.kg(-0.75).d(-1) liquid diet containing 70% corn
      oil with or without 2 g.kg(-1).d(-1) NAC i.g. for 65 d. Hepatic steatosis was not
      influenced by dietary supplementation with NAC; however, the liver pathology
      score was lower (P </= 0.05) and NAC provided partial protection against alanine
      aminotransferase release (P </= 0.05). NAC attenuated increased hepatic oxidative
      stress (TBARS; P </= 0.05) and prevented increases in cytochrome P450 2E1
      apoprotein and mRNA and in tumor necrosis factor-alpha (TNFalpha) mRNA. Titers of
      auto-antibodies against proteins adducted to lipid peroxidation products were
      lower in serum of the NAC group than in the 70% corn oil group (P </= 0.05). NAC
      also decreased Picosirius red staining of collagen, a marker of fibrosis.
      However, markers of hepatic stellate cell activation were unaffected. Using NAC
      in a TEN model of NASH, we have demonstrated that NAC prevents many aspects of
      NASH progression by decreasing development of oxidative stress and subsequent
      increases in TNFalpha but does not block development of steatosis.

PMID- 18806096
TI  - Iron injection restores brain iron and hemoglobin deficits in perinatal copper
      deficient rats.
AB  - Copper (Cu) deficiency during perinatal development in rats is associated with
      anemia, lower plasma iron (Fe), and brain Fe. Experiments were conducted to
      inject Fe dextran into Cu-deficient (Cu-) rat pups to attempt to reverse these
      conditions. Previous work with older Cu- rats did not reverse anemia following Fe
      injection. Dams began Cu-adequate (Cu+) or Cu- dietary treatments starting at
      embryonic d 7 and lasting through weaning. In Expt. 1, pups from each dietary
      treatment were given a single dose of Fe, 20 mg Fe/kg, or saline (S) at postnatal
      d 11 (P11). Plasma Fe and hemoglobin were higher in the Fe-injected groups at
      P13. Brain Fe deficit and brain transferrin receptor enhancement were eliminated
      in the Cu- group injected with Fe compared with Cu-S pups, supporting an
      association between low plasma Fe and low brain Fe. In Expt. 2, Fe treatment was
      increased to 45 mg Fe/kg. Four injections were given between P5 and P18 (total
      dose, 5-7 mg Fe). At P20, Fe concentrations in 4 brain regions (cortex,
      cerebellum, medulla/pons, and hypothalamus) generally were higher in all groups
      than in Cu-S pups. At P25, impaired vibrissae-elicited foot placement was evident
      in Cu-S rats and was not improved by Fe injection. However, at P26, the brain Fe
      deficit in Cu-S pups was eliminated by Fe injection. Fe injections in Cu- pups
      raised plasma Fe, brain Fe, and hemoglobin but did not reverse low cytochrome c
      oxidase or abnormal striatal behavior.

PMID- 18806097
TI  - Activation of AMP-activated protein kinase by 5-aminoimidazole-4-carboxamide-1
      beta-D-ribonucleoside prevents leucine-stimulated protein synthesis in rat
      skeletal muscle.
AB  - Several stress conditions are characterized by activation of 5'-AMP-activated
      protein kinase (AMPK) and the development of leucine resistance in skeletal
      muscle. In the present study, we determined whether direct activation of the AMPK
      by 5-aminoimidazole-4-carboxamide-1-beta-D-ribonucleoside (AICAR) prevents the
      characteristic leucine-induced increase in protein synthesis by altering
      mammalian target of rapamycin (mTOR) signal transduction. Rats were injected with
      AICAR or saline (Sal) and 1 h thereafter received an oral gavage of leucine (or
      Sal). Efficacy of AICAR was verified by increased AMPK phosphorylation. AICAR
      decreased basal in vivo muscle (gastrocnemius) protein synthesis and completely
      prevented the leucine-induced increase, independent of a change in muscle adenine
      nucleotide concentration. AICAR also prevented the hyperphosphorylation of
      eukaryotic initiation factor (eIF) 4E binding protein (4E-BP1), ribosomal protein
      S6 kinase (S6K1), S6, and eIF4G in response to leucine, suggesting a decrease in
      mTOR activity. Moreover, AICAR prevented the leucine-induced redistribution of
      eIF4E from the inactive eIF4E.4E-BP1 to the active eIF4E.eIF4G complex. This
      ability of AICAR to produce muscle leucine resistance could not be attributed to
      a change in phosphorylation of tuberous sclerosis complex (TSC)2, the formation
      of a TSC1.TSC2 complex, the binding of raptor with mTOR, or the phosphorylation
      of eukaryotic elongation factor-2. However, the inhibitory actions of AICAR were
      associated with reduced phosphorylation of proline-rich Akt substrate-40 and
      increased phosphorylation of raptor, which represent potential mechanisms by
      which AICAR might be expected to inhibit leucine-induced increases in mTOR
      activity and protein synthesis under in vivo conditions.

PMID- 18806098
TI  - The small intestine proteome is changed in preterm pigs developing necrotizing
      enterocolitis in response to formula feeding.
AB  - Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency in
      newborn premature infants. Clinical studies show increased incidence of NEC in
      premature infants with enteral formula feeding; however, pathogenesis remains
      unclear. To identify the NEC-related proteins for molecular mechanisms, we
      applied proteomics analysis to characterize changes in the protein expression
      profile of newborn premature piglet intestines with NEC developed after enteral
      formula feeding for 24 h. Changes in protein expression were identified using 2
      dimensional gel electrophoresis and peptide mass fingerprinting with MS as well
      as western blotting analysis. Nineteen differentially expressed proteins were
      identified and these have roles in oxidative stress, chaperone, signal
      transduction, protein folding and degradation, oxygen transport, signal
      transduction, and energy metabolism. Proteins with increased levels include
      manganese-containing superoxide dismutase and hemoglobin subunit and proteins
      with decreased expression include sorbitol dehydrogenase, mitochondrial aldehyde
      dehydrogenase 2, glucose-regulated protein 75, CRY protein, snail homolog 3,
      thyroid hormone-binding protein precursor, and DJ1 (Parkinson's disease 7) etc.
      The data provided novel mechanistic insights into the pathogenesis of NEC and the
      insults of a formulated diet to the premature gut.

PMID- 18806099
TI  - Dietary (n-3) long-chain polyunsaturated fatty acids inhibit ischemia and
      reperfusion arrhythmias and infarction in rat heart not enhanced by ischemic
      preconditioning.
AB  - Ischemic preconditioning (IPC) and (n-3) PUFA are both cardioprotective. This
      study compared effects of dietary fish oil, IPC, and their interactions on heart
      function and injury during myocardial ischemia and reperfusion. Male Wistar rats
      were fed diets containing 10% wt:wt fat comprising either 7% high-docosahexaenoic
      acid (DHA) [22:6(n-3)] tuna fish oil + 3% olive oil [(n-3) PUFA]; 5% sunflower
      seed oil + 5% olive oil [(n-6) PUFA]; or 7% beef tallow + 3% olive oil [saturated
      fat (SF)] for 6 wk. In control experiments, isolated perfused hearts were
      subjected to 30-min regional ischemia and reperfused for 120 min. The IPC hearts
      were subjected to 3 cycles of 5-min global ischemia before the ischemia and
      reperfusion. Control (n-3) PUFA hearts had significantly lower heart rate,
      coronary flow, end diastolic pressure, maximum relaxation rate, and ischemic and
      reperfusion arrhythmias. In reperfusion, they had greater developed pressure and
      maximum relaxation rate and smaller infarct (10.9 +/- 0.6% ischemic zone, n = 6)
      than (n-6) PUFA (47.4 +/- 0.3%, n = 6) or SF (50.3 +/- 0.3%, n = 6). Compared
      with control, IPC significantly improved heart function and reduced infarct in (n
      6) PUFA (11.8 +/- 0.4%, n = 6) and SF hearts (13.1 +/- 0.1%, n = 6). Heart
      function and infarct [(n-3) PUFA 9.6 +/- 0.1%, n = 6] did not differ among
      dietary IPC groups. Arrhythmias, significantly reduced by IPC in (n-6) PUFA and
      SF hearts, were significantly lower in (n-3) PUFA IPC hearts. Dietary fish oil
      induces a form of preconditioning, nutritional preconditioning, limiting ischemic
      cardiac injury, and myocardial infarction and endows cardioprotection as powerful
      as IPC, which provides no additional protection in (n-3) PUFA hearts.

PMID- 18806100
TI  - Impaired postprandial endothelial function depends on the type of fat consumed by
      healthy men.
AB  - Postprandial lipemia impairs endothelial function possibly via an oxidative
      stress mechanism. A stearic acid-rich triacylglycerol (TAG) (shea butter) results
      in a blunted postprandial increase in plasma TAG compared with an oleic acid-rich
      TAG; however, its acute effects on endothelial function and oxidative stress are
      unknown. A randomized crossover trial (n = 17 men) compared the effects of 50 g
      fat, rich in stearic acid [shea butter blend (SA)] or oleic acid [high oleic
      sunflower oil (HO)], on changes in endothelial function [brachial artery flow
      mediated dilatation (FMD)], arterial tone [pulse wave analysis (PWA), and carotid
      femoral pulse wave velocity (PWV(c-f))], and oxidative stress (plasma 8
      isoprostane F2alpha) at fasting and 3 h following the test meals. The
      postprandial increase in plasma TAG was lower (66% lower incremental area under
      curve) following the SA meal [28.3 (9.7, 46.9)] than after the HO meal [83.4
      (57.0, 109.8); P < 0.001] (geometric means with 95% CI, arbitary units).
      Following the HO meal, there was a decrease in FMD [-3.0% (-4.4, -1.6); P <
      0.001] and an increase in plasma 8-isoprostane F2alpha [10.4ng/L (3.8, 16.9); P =
      0.005] compared with fasting values, but no changes followed the SA meal. The
      changes in 8-isoprostane F2alpha and FMD differed between meals and were 14.0
      ng/L (6.4, 21.6; P = 0.001) and 1.75% (0.10, 3.39; P = 0.02), respectively. The
      reductions in PWA and PWV c-f did not differ between meals. This study
      demonstrates that a stearic acid-rich fat attenuates the postprandial impairment
      in endothelial function compared with an oleic acid-rich fat and supports the
      hypothesis that postprandial lipemia impairs endothelial function via an increase
      in oxidative stress.

PMID- 18806101
TI  - Long-chain (n-3) polyunsaturated fatty acids prevent metabolic and vascular
      disorders in fructose-fed rats.
AB  - The crossover relationship between cardiometabolic risk, in terms of insulin
      resistance and vascular dysfunction, and the fatty acid (FA) profile of insulin
      sensitive tissues as well as the dietary FA impact has almost never been explored
      in the same experiment. In this study, the intake of alpha-linolenic acid (ALA)
      alone and/or with its higher metabolites, eicosapentaenoic acid (EPA), and
      docosahexaenoic acid (DHA) were evaluated in a nonobese, hypertriglyceridemic and
      insulin-resistant rat model, that exhibits the 2 main characteristics of
      metabolic syndrome. Wistar rats were fed either a cornstarch and (n-6) PUFA-based
      diet (C-N6) or a 66% fructose diet over a 10-wk period. Fructose-fed rats
      received a diet containing ALA alone (F-ALA group) or ALA plus EPA and DHA (F-LC3
      group) or no (n-3) PUFA (F-N6 group). The 10-wk high-fructose diet (F-N6) induced
      an insulin-resistant state, as assessed by glucose and insulin tolerance tests.
      Insulin resistance was linked to a specific FA pattern in insulin-sensitive
      tissues, which probably involved modifications of Delta9, Delta6, and Delta5
      desaturases. This pathological status was related to high cardiovascular risk as
      assessed by increases in systolic and diastolic blood pressures and particularly
      by the increase of pulse pressure, an index of vascular stiffness obtained from
      telemetry investigations. The (n-3) experimental diets prevented changes in the
      FA patterns in insulin-sensitive tissues, insulin resistance, and vascular
      dysfunction. This beneficial effect was large with an intake of long chain (n-3)
      PUFA (ALA+EPA+DHA) and to a lesser extent with dietary ALA alone.

PMID- 18806102
TI  - A 9-cis beta-carotene-enriched diet inhibits atherogenesis and fatty liver
      formation in LDL receptor knockout mice.
AB  - Our aim was to study the effect of 9-cis beta-carotene-rich powder of the alga
      Dunaliella bardawil on lipid profile, atherogenesis, and liver steatosis in high
      fat diet-fed LDL receptor knockout mice. In 4 sets of experiments, mice were
      distributed into the following groups: control, fed an unfortified diet;
      Dunaliella 50, fed a diet composed of 50% 9-cis and 50% all-trans beta-carotene;
      Dunaliella 25, fed a diet containing 25% 9-cis and 75% all-trans beta-carotene;
      beta-carotene-deficient Dunaliella, fed beta-carotene-deficient Dunaliella
      powder; and all-trans beta-carotene, fed a synthetic all-trans beta-carotene. All
      fortified diets contained 0.6% total beta-carotene. Algal 9-cis beta-carotene was
      absorbed by the mice and accumulated in the liver. Synthetic all-trans beta
      carotene was not converted to 9-cis beta-carotene. Dunaliella 50 inhibited high
      fat diet-induced plasma cholesterol elevation by 40-63% and reduced cholesterol
      concentrations in the atherogenic VLDL and LDL. Atherosclerotic lesion area in
      mice treated with Dunaliella 50 was 60-83% lower compared with mice fed the high
      fat diet alone. beta-Carotene-deficient Dunaliella did not influence plasma
      cholesterol and atherogenesis, suggesting that beta-carotene is essential for a
      Dunaliella protective effect. Moreover, by administrating Dunaliella powder
      containing different levels of 9-cis and all-trans beta-carotene isomers, we
      found that the effect on plasma cholesterol concentration and atherogenesis is 9
      cis-dependent. Dunaliella 50 also inhibited fat accumulation and inflammation in
      the livers of mice fed a high-fat diet, which was accompanied by reduced mRNA
      levels of inflammatory genes. These results in mice suggest that 9-cis beta
      carotene may have the potential to inhibit atherogenesis in humans.

PMID- 18806103
TI  - High vitamin C intake is associated with lower 4-year bone loss in elderly men.
AB  - Vitamin C is essential for collagen formation and normal bone development. We
      evaluated associations of total, supplemental, and dietary vitamin C intake with
      bone mineral density (BMD) at the hip [femoral neck, trochanter], spine, and
      radial shaft and 4-y BMD change in elderly participants from the Framingham
      Osteoporosis Study. Energy-adjusted vitamin C intakes were estimated from the
      Willett FFQ in 1988-89. Mean BMD and 4-y BMD change was estimated, for men and
      women, by tertile/category of vitamin C intake, adjusting for covariates. We
      tested for interaction with smoking, calcium, and vitamin E intake. Among 334 men
      and 540 women, the mean age was 75 y and mean vitamin D intake was 8.25 mug/d
      (women) and 8.05 mug/d (men). We observed negative associations between total and
      supplemental vitamin C intake and trochanter-BMD among current male smokers (P
      trend = 0.01). Among male nonsmokers, total vitamin C intake was positively
      associated with femoral neck BMD (P-trend = 0.04). Higher total vitamin C intake
      was associated with less femoral neck and trochanter-BMD loss in men with low
      calcium (all P-trend </= 0.03) or vitamin E intakes (all P-trend = 0.03). Higher
      dietary vitamin C intake tended to be associated with lower femoral neck-BMD loss
      (P-trend = 0.09). These associations were attenuated but retained borderline
      significance (P-trend < 0.1) after adjusting for potassium intake (a marker of
      fruit and vegetable intake), suggesting that vitamin C effects may not be
      separated from other protective factors in fruit and vegetables. Null
      associations were observed among women. These results suggest a possible
      protective role of vitamin C for bone health in older men.

PMID- 18806104
TI  - Regular consumption of dark chocolate is associated with low serum concentrations
      of C-reactive protein in a healthy Italian population.
AB  - Dark chocolate contains high concentrations of flavonoids and may have
      antiinflammatory properties. We evaluated the association of dark chocolate
      intake with serum C-reactive protein (CRP). The Moli-sani Project is an ongoing
      cohort study of men and women aged >/=35 y randomly recruited from the general
      population. By July 2007, 10,994 subjects had been enrolled. Of 4849 subjects
      apparently free of any chronic disease, 1317 subjects who declared having eaten
      any chocolate during the past year (mean age 53 +/- 12 y; 51% men) and 824
      subjects who ate chocolate regularly in the form of dark chocolate only (50 +/-
      10 y; 55% men) were selected. High sensitivity-CRP was measured by an
      immunoturbidimetric method. The European Prospective Investigation into Cancer
      and Nutrition FFQ was used to evaluate nutritional intake. After adjustment for
      age, sex, social status, physical activity, systolic blood pressure, BMI,
      waist:hip ratio, food groups, and total energy intake, dark chocolate consumption
      was inversely associated with CRP (P = 0.038). When adjusted for nutrient intake,
      analyses showed similar results (P = 0.016). Serum CRP concentrations [geometric
      mean (95% CI)] univariate concentrations were 1.32 (1.26-1.39 mg/L) in
      nonconsumers and 1.10 (1.03-1.17 mg/L) in consumers (P < 0.0001). A J-shaped
      relationship between dark chocolate consumption and serum CRP was observed;
      consumers of up to 1 serving (20 g) of dark chocolate every 3 d had serum CRP
      concentrations that were significantly lower than nonconsumers or higher
      consumers. Our findings suggest that regular consumption of small doses of dark
      chocolate may reduce inflammation.

PMID- 18806105
TI  - Retinol and riboflavin supplementation decreases the prevalence of anemia in
      Chinese pregnant women taking iron and folic Acid supplements.
AB  - In rural China, many pregnant women in their third trimester suffer from anemia
      (48%) and iron deficiency (ID; 42%), often with coexisting deficiencies of
      retinol and riboflavin. We investigated the effect of retinol and riboflavin
      supplementation in addition to iron plus folic acid on anemia and subjective well
      being in pregnant women. The study was a 2-mo, double-blind, randomized trial.
      Subjects (n = 366) with anemia [hemoglobin (Hb) </= 105 g/L] were randomly
      assigned to 4 groups, all receiving 60 mg/d iron and 400 mug/d folic acid. The
      iron+folic acid (IF) group (n = 93) served as reference, the iron+folic
      acid+retinol group (IFA) (n = 91) was treated with 2000 mug retinol, the
      iron+folic acid+riboflavin group (IFB) (n = 91) with 1.0 mg riboflavin, and the
      iron+folic acid+retinol+riboflavin group (IFAB) (n = 91) with retinol and
      riboflavin. After the 2-mo intervention, the Hb concentration increased in all 4
      groups (P < 0.001). The increase in the IFAB group was 5.4 +/- 1.1 g/L greater
      than in the IF group (P < 0.001). The reduced prevalence of anemia (Hb < 110g/L)
      and ID anemia were significantly greater in the groups supplemented with retinol
      and /or riboflavin than in the IF group. Moreover, gastrointestinal symptoms were
      less prevalent in the IFA group than in the IF group (P < 0.05) and improved well
      being was more prevalent in the groups receiving additional retinol and/or
      riboflavin than in the IF group (P < 0.05). Thus, a combination of iron, folic
      acid, retinol, and riboflavin was more effective than iron plus folic acid alone.
      Multimicronutrient supplementation may be worthwhile for pregnant women in rural
      China.

PMID- 18806106
TI  - Adherence rates to the Mediterranean diet are low in a representative sample of
      Greek children and adolescents.
AB  - Data from studies in pediatric samples exploring adherence to the Mediterranean
      diet are scarce. The aim of the present work was to explore adherence to a
      Mediterranean diet pattern in a representative sample of Greek children and
      adolescents. The study sample (n = 1305, 3-18 y) was representative of the Greek
      pediatric population in terms of sex and age. Information on participants'
      sociodemographic, anthropometric, and lifestyle characteristics were collected
      through telephone interviews. Adherence to the Mediterranean diet guidelines for
      adults and to the general dietary guidelines for children was evaluated using
      KIDMED scores: the higher the score, the more favorable the dietary pattern. The
      Goldberg cut-off limits for the ratio of energy intake:basal metabolic rate were
      used to evaluate dietary underreporting and children were accordingly classified
      as low energy reporters (LER) or non-LER. Only 11.3% of children and 8.3% of
      adolescents had an optimal KIDMED score (>/=8). In adolescents, partial
      correlation analysis revealed a negative weak association between KIDMED and BMI
      (r = -0.092; P = 0.031), which remained significant in the non-LER subgroup (r = 
      0.137, P = 0.011). Multiple regression analysis revealed that higher KIDMED
      scores were associated, in non-LER children, with less time spent on sedentary
      activities (P = 0.002) and higher paternal education (P = 0.050), whereas in
      adolescents, with younger age (P = 0.001), less time spent on sedentary
      activities (P = 0.015), higher maternal education (P = 0.014), and higher eating
      frequency (P = 0.041). In conclusion, low adherence rates to the Mediterranean
      diet were observed in Greek children and adolescents; this evidence needs to be
      further explored regarding its impact on health and disease.

PMID- 18806107
TI  - Urinary 3-(3,5-dihydroxyphenyl)-1-propanoic acid, an alkylresorcinol metabolite,
      is a potential biomarker of whole-grain intake in a U.S. population.
AB  - 5-n-Alkylresorcinols (AR) are a major group of phenolic compounds in whole-grain
      wheat, rye, and barley. As such, they may serve as potential biomarkers of whole
      grain intake, because they are quantifiable intact in plasma and as metabolites
      in urine. We examined relationships between 12-h urinary excretion of AR
      metabolite 3-(3,5-dihydroxyphenyl)-1-propanoic acid (DHPPA) and self-reported
      habitual intake of whole-grain foods measured by 3-d food record (3DFR) and FFQ.
      Urine samples from 100 men and women were analyzed for DHPPA using HPLC with
      coularray detection. DHPPA excretion ranged from 1.3 to 99.4 (mean +/- SE, 14.0
      +/- 1.5) mumol/12 h. Whole-grain food intake, as determined by 3DFR and FFQ and
      adjusted for BMI and energy and fiber intake, was significantly associated with
      12-h urinary DHPPA excretion. Based on 3DFR, whole-grain wheat + rye consumers
      had a 44% higher DHPPA excretion than nonconsumers [ratio of excretion (95% CI) =
      1.44 (1.04, 1.97); P = 0.029]. Using whole-grain intake estimated by FFQ, a
      serving increase in whole-grain wheat + rye intake increased DHPPA excretion by
      94% [ratio of excretion (95% CI) = 1.94 (1.35, 2.78); P = 0.001] and a serving
      increase in whole grains as defined more broadly in epidemiologic studies of
      whole-grain intake and disease risk (whole-grain wheat, rye, oats, and corn)
      increased DHPPA by 67% [ratio of excretion (95% CI) = 1.67 (1.28, 2.17); P <
      0.0001]. This study supports the potential utility of urinary DHPPA as a
      biomarker of whole-grain intake in a U.S. population.

PMID- 18806108
TI  - Soy- and rice-based processed complementary food increases nutrient intakes in
      infants and is equally acceptable with or without added milk powder.
AB  - Processed complementary foods (PCF) might mitigate several complementary feeding
      barriers in developing countries. Efficacy trials, however, have not shown
      substantial improvements in child growth, possibly due to inadequate formative
      research to assess acceptability and identify pitfalls. Milk powder might improve
      palatability of PCF but incurs a higher cost. We compared the acceptability of an
      instant soy-rice PCF without (SR) and with (SRM) milk powder. Best practices for
      formative evaluation of PCF are not established. We therefore compared findings
      from randomized trials of SR vs. SRM in 1-d sensory tests (n = 71 mother-infant
      dyads) vs. Trials of Improved Practices (TIPs), a 2-wk in-home mixed methods
      evaluation (n = 54 dyads). TIPs included interviews, disappearance rates,
      observations, and 24-h dietary recalls to assess acceptance, consumption of the
      50 g/d ration, and impact on diet. Although mothers preferred SRM to SR in the
      sensory tests, children in the TIPs consumed >50 g/d of SR (87 +/- 9 g/d) and SRM
      (89 +/- 8 g/d) with no difference between the foods (P = 0.55). Despite some
      replacement of family food, energy (574 kJ/d; P < 0.001) and protein (19 g
      protein/d; P < 0.001) increased in both groups. Mothers' preferences for milk,
      more sugar in SR, and preparation with hot water were concerns raised in the
      sensory tests that proved insignificant in TIPs. However, TIPs uncovered new
      concerns of overconsumption and food safety. We found milk did not improve the
      acceptability of the soy-rice PCF and recommend TIPs as a useful tool for
      formative research of PCF interventions.

PMID- 18806109
TI  - Zinc supplementation improved length growth only in anemic infants in a multi
      country trial of iron and zinc supplementation in South-East Asia.
AB  - Data from 4 randomized, placebo-controlled, double-blind trials in Indonesia,
      Thailand, and Vietnam, the South-East Asian Multicountry Trial on Iron and Zinc
      supplementation in Infants (SEAMTIZI), were pooled to investigate the effects of
      iron and zinc supplementation infant growth. Infants (n = 2451) aged 4-6 mo old
      were supplemented with iron (10 mg/d) and/or zinc (10 mg/d) for 6 mo. Overall,
      neither iron nor zinc supplementation prevented the progressive growth faltering
      during infancy, which is common in many developing countries. However, infants
      who received zinc were less likely to be stunted at the end of the
      supplementation period (odds ratio 0.80; 95% CI 0.64-1.0). Boys had a 30% higher
      risk of being stunted at the end of the study than girls (P < 0.01). Baseline
      factors modified the effect of supplementation, with infants anemic at baseline
      (hemoglobin < 105 g/L) benefiting from zinc supplementation, with an estimated
      increase in height-for-age Z-score (HAZ) score of 0.17 (P < 0.01), but with no
      effect of zinc supplementation on growth in infants not anemic at baseline. Iron
      supplementation negatively affected linear growth in infants with a birth weight
      of >3500 g (estimated effect size, -0. 14 HAZ score; P < 0.01), but with no
      significant effect in infants with a lower birth weight. This study shows that
      blanket supplementation of infants with iron or zinc will not be beneficial to
      all recipients and may have adverse effects in some. Hence, interventions such as
      iron and zinc supplementation for infants should be restricted to subgroups in
      which there is a clear benefit and baseline factors should be considered and
      characterized before implementing new policies.

PMID- 18806110
TI  - Fractional protein synthesis rates are similar when measured by intraperitoneal
      or intravenous flooding doses of L-[ring-2H5]phenylalanine in combination with a
      rapid regimen of sampling in piglets.
AB  - Fractional protein synthesis rates (FSR) are widely measured by the flooding dose
      technique via either an i.g. or an i.v. route. This study was conducted to
      compare differences in tracer incorporation and FSR in organs and tissues of fed
      piglets. The piglets were surgically implanted with catheters and randomly
      assigned to receive a flooding dose of Phe (1.5 mmol/kg body weight, 40 percent
      molar enrichment with [(2)H(5)]Phe) in saline administered via an i.p. or an i.v.
      route. [(2)H(5)]Phe free-pool enrichment in plasma increased logarithmically (P <
      0.05) from 0 to 25% in the i.p. group, whereas it rose to a peak level within 3
      min of the tracer injection and then decreased linearly (P < 0.05) in the i.v.
      group. Intracellular free-pool tracer enrichments in organs and tissues were
      within the range of the values measured for the plasma-free pool (25-27%),
      reaching the flooding status. Administration of the tracer via the i.p. and i.v.
      routes induced a logarithmical pattern (P < 0.05) of a surge in plasma cortisol
      concentrations within 30 min. Measurements of FSR in plasma, cardiac muscle, and
      skeletal muscles were lower (P < 0.05) in the i.p. than in the i.v. group due to
      the adverse effect of cortisol surge being more dramatic (P < 0.05) in the i.p.
      than in the i.v. group at 30 min of the post-tracer administration. We conclude
      that FSR may be measured by the flooding dose through an i.p. or an i.v. route
      and the i.p. route may underestimate FSR by the flooding dose for plasma, cardiac
      muscle, and skeletal muscles. This concern may be addressed by a fast regimen of
      sampling to be completed within 12-20 min after an i.p. route of tracer
      injection.

PMID- 18806112
TI  - Nutrient risk assessment as a tool for providing scientific assessments to
      regulators.
AB  - Regulatory officials world-wide are paying attention to the process for
      establishing the upper level of intake for nutrient substances. The rapidly
      expanding use of dietary supplements, fortified foods, and functional foods,
      coupled with increased trade in these products, has focused attention on ensuring
      their safety and on harmonizing standards internationally. The more traditional
      approaches, in which the regulators either provided no standards for upper levels
      of intake or developed standards based on some arbitrary multiple of the intake
      level known to provide an adequate amount of the nutrient, are recognized as
      outdated or inappropriate for the emerging issues. Preferred approaches are those
      that rely on the systematic scientific assessment of risk to determine the levels
      of intake below which no harm may occur. The scientific study of risk is playing
      an increased role in establishing the regulatory upper levels of "safe" nutrient
      intake. Risk assessment, as a component of risk analysis, offers a scientific
      basis for regulatory decision-making regarding the regulators' task associated
      with specifying safe upper levels of intake for nutrient substances. This article
      describes the key components of risk assessment as they are applied within the
      nutrition field. Although regulatory frameworks vary from country to country and
      all countries retain their right to determine their own level of protection,
      regulatory systems operate most effectively and are more likely to converge
      toward harmonization if they are informed by independent, organized, and
      scientific reviews that are conducted systematically in a transparent manner.

PMID- 18806113
TI  - Expanded approach to tolerable upper intake guidelines for nutrients and
      bioactive substances.
AB  - The original tolerable upper intake level (UL) method greatly improved the
      application of risk assessment to the evaluation of nutrient safety for humans,
      but a UL is only set where the data establish a hazard resulting from high
      intakes. Absence of a UL for those nutrients with no established hazard has been
      misinterpreted by regulators and resulted in overly restrictive policies. To
      prevent such misinterpretation, the observed safe level (OSL) was developed and
      defined as "the highest intake with convincing evidence of safety, even if there
      are no established adverse effects at any level." More recently, a FAO/WHO report
      gave a similar definition for the highest observed intake (HOI). Another
      disadvantage of the UL method is the application of arbitrary uncertainty factors
      (UF). An alternative to the traditional adjustment for uncertainty involves
      arranging the data in decreasing order of daily intake, followed by evaluation of
      each trial for quantity and quality of data. Studies are selected downward until
      no adverse effects are observed in a trial of sufficient quality to justify no
      further correction for uncertainty (i.e. selection of data that qualify for UF =
      1). Thus, the no observed adverse effect level or OSL selected requires no
      further adjustment for uncertainty. For supplemental intakes of some vitamins,
      many bioactive substances, and most amino acids, no adverse effects that are
      clearly related to high intakes have been established, but where the dataset is
      sufficiently robust, application of the OSL-HOI technique can provide risk
      assessment values.

PMID- 18806114
TI  - An approach to defining the upper safe limits of amino acid intake.
AB  - The existing data on the safe upper limits of amino acid intake in humans is
      essentially observational; how much do individuals ingest and what side effects
      do they have? There are numerous studies in humans comparing the effects of high
      doses of amino acids given as protein bound vs. as free amino acids. These
      studies have shown that protein-bound amino acids have much less effect on plasma
      levels of the test amino acid, because protein intake stimulates protein
      synthesis as another sink for the increased amino acid intake. In practice, the
      highest amino acid intakes occur with free amino acid supplements that may be
      ingested by athletes who believe that the amino acids will benefit them in
      training and/or performance. Previously, in a piglet study, we were able to
      define the point at which maximal phenylalanine oxidation occurred, above which
      plasma phenylalanine concentration and body balance rose exponentially. We regard
      this value of maximal disposal (oxidation) of an amino acid as one metabolic
      marker of the upper limit of intake. Recently, others have demonstrated a similar
      maximal oxidation rate for leucine in rats. Based on these experimental data and
      the paucity of published human data in controlled experiments, we think that a
      systematic approach needs to be undertaken to define the maximal oxidation rate
      for all dietary indispensable amino acids and other amino acids that may be
      ingested in excess by humans. We believe that this will provide a rational basis
      to begin to define the upper limits of tolerance for dietary amino acids.
      However, some amino acids, such as threonine and methionine, will be more
      difficult to study, because they have more than 1 route of disposal or very
      complex metabolic regulation, in which case defining their upper limits will be
      more multifaceted.

PMID- 18806115
TI  - Glutamine metabolism and function in relation to proline synthesis and the safety
      of glutamine and proline supplementation.
AB  - At normal intakes, dietary glutamine and glutamate are metabolized by the small
      intestine and essentially all glutamine within the body is synthesized de novo
      through the action of glutamine synthetase. The major sites of net glutamine
      synthesis are skeletal muscle, lung, and adipose tissue and, under some
      conditions, the liver. In addition to the small intestine, where glutamine is the
      major respiratory fuel, other sites of net glutamine utilization include the
      cells of the immune system, the kidneys, and the liver. The intestine expresses
      pyrroline 5-carboxylate (P5C) synthase, which means that proline is an end
      product of intestinal glutamine catabolism. Proline can also be synthesized from
      ornithine and the exact contribution of the 2 pathways is not certain. Infusion
      of proline i.v. to increase circulating concentrations is associated with
      increased proline oxidation and decreased proline synthesis. In contrast,
      conditions of proline insufficiency, after feeding low-proline diets or in
      response to high rates of proline catabolism in burn patients, do not result in
      increased proline synthesis. Glutamine supplementation is widespread and up to
      0.57-0.75 g.kg(-1).d(-1) is well tolerated. Similarly, the only study of proline
      supplementation, in which patients with gyrate atrophy were given 488 mg.kg(
      1).d(-1), reported no deleterious side effects. In the absence of controlled
      trials, it is currently not possible to estimate a safe upper limit for either of
      these 2 amino acids.

PMID- 18806116
TI  - The metabolism of proline as microenvironmental stress substrate.
AB  - Proline, a unique proteogenic secondary amino acid, has its own metabolic system
      with special features. Recent findings defining the regulation of this system led
      us to propose that proline is a stress substrate in the microenvironment of
      inflammation and tumorigenesis. The criteria for proline as a stress substrate
      are: 1) the enzymes utilizing proline respond to stress signaling; 2) there is a
      large, mobilizable pool of proline; and 3) the metabolism of proline serves
      special stress functions. Studies show that the proline-utilizing enzyme, proline
      oxidase (POX)/proline dehydrogenase (PRODH), responds to genotoxic, inflammatory,
      and nutrient stress. Proline as substrate is stored as collagen in extracellular
      matrix, connective tissue, and bone and it is rapidly released from this
      reservoir by the sequential action of matrix metalloproteinases, peptidases, and
      prolidase. Special functions include the use of proline by POX/PRODH to generate
      superoxide radicals that initiate apoptosis by intrinsic and extrinsic pathways.
      Under conditions of nutrient stress, proline is an energy source. It provides
      carbons for the tricarboxylic acid cycle and also participates in the proline
      cycle. The latter, catalyzed by mitochondrial POX and cytosolic pyrroline-5
      carboxylate reductase, shuttles reducing potential from the pentose phosphate
      pathway into mitochondria to generate ATP and oxidizing potential to activate the
      cytosolic pentose phosphate pathway.

PMID- 18806117
TI  - Inborn errors of proline metabolism.
AB  - l-Proline concentration is primarily related to the balance of enzymatic
      activities of proline dehydrogenase [proline oxidase (POX)] and Delta-1-pyrroline
      5-carboxylate (P5C) reductase. As a result, P5C plays a pivotal role in
      maintaining the concentration of proline in body fluids and inborn errors of P5C
      metabolism lead to disturbance of proline metabolism. Several inborn errors of
      proline metabolism have been described. Hyperprolinemia type I (HPI) is a result
      of a deficiency in POX. The POX gene (PRODH) is located on chromosome 22
      (22q11.2) and this region is deleted in velo-cardio-facial syndrome, a congenital
      malformation syndrome. In addition, this gene locus is related to susceptibility
      to schizophrenia. The other type of hyperprolinemia is HPII. It is caused by a
      deficiency in P5C dehydrogenase activity. Hypoprolinemia, on the other hand, is
      found in the recently described deficiency of P5C synthetase. This enzyme defect
      leads to hyperammonemia associated with hypoornithinemia, hypocitrullinemia, and
      hypoargininemia other than hypoprolinemia. Hyperhydroxyprolinemia is an autosomal
      recessive inheritance disorder caused by the deficiency of hydroxyproline
      oxidase. There are no symptoms and it is believed to be a benign metabolic
      disorder. The deficiency of ornithine aminotransferase causes transient
      hyperammonemia during early infancy due to deficiency of ornithine in the urea
      cycle. In later life, gyrate atrophy of the retina occurs due to
      hyperornithinemia, a paradoxical phenomenon. Finally, prolidase deficiency is a
      rare autosomal recessive hereditary disease. Prolidase catalyzes hydrolysis of
      dipeptide or oligopeptide with a C-terminal proline or hydroxyproline and its
      deficiency can cause mental retardation and severe skin ulcers.

PMID- 18806118
TI  - Proline precursors to sustain Mammalian collagen synthesis.
AB  - Biochemically, one-third of the collagen molecule is composed of glycine. The
      next largest amino acid component is formed by proline (PRO) and hydroxyproline,
      which together comprise approximately 23% of the collagen molecule. The best
      method to support wound collagen biosynthesis is to provide adequate host
      nutrition, assuring adequate provision of calories and protein. However, despite
      adequate nutrition, clinically, there is a need to enhance collagen synthesis and
      research has focused on methods to enhance collagen precursor availability. PRO
      biosynthesis is related to both the citric acid cycle and the urea cycle. During
      the early phases of wound healing, wound fluid PRO levels are at least 50% higher
      than plasma levels, suggesting active import of PRO into the wound. Providing
      additional PRO in the diet to enhance PRO bioavailability for collagen
      biosynthesis does not result in increased collagen accumulation. Provision of
      other citric cycle precursors such as glutamine also does not enhance wound
      collagen synthesis. In looking at other PRO biosynthetic pathways, the arginine
      (ARG) --> ornithine (ORN) --> glutamic semialdehyde --> PRO pathway looks the
      most promising. ARG administration in quantities above those required for growth
      and reproduction results in a marked enhancement in wound collagen deposition.
      This effect is also shared by ORN, which cannot replace ARG for growth
      requirement but shares many of its biological and pharmacological activities.
      Several mechanisms have been postulated to explain the positive effect of ARG on
      wound healing, although none have been firmly proven. In conclusion, ARG and ORN
      supplementation are most effective in increasing collagen deposition, but whether
      this is accomplished by conversion to PRO is uncertain.

PMID- 18806119
TI  - Nonnutritive effects of glutamine.
AB  - Glutamine is the most abundant free amino acid of the human body. Besides its
      role as a constituent of proteins and its importance in amino acid
      transamination, glutamine has regulatory capacity in immune and cell modulation.
      Glutamine deprivation reduces proliferation of lymphocytes, influences expression
      of surface activation markers on lymphocytes and monocytes, affects the
      production of cytokines, and stimulates apoptosis. Moreover, glutamine
      administration seems to have a positive effect on glucose metabolism in the state
      of insulin resistance. Glutamine influences a variety of different molecular
      pathways. Glutamine stimulates the formation of heat shock protein 70 in
      monocytes by enhancing the stability of mRNA, influences the redox potential of
      the cell by enhancing the formation of glutathione, induces cellular anabolic
      effects by increasing the cell volume, activates mitogen-activated protein
      kinases, and interacts with particular aminoacyl-transfer RNA synthetases in
      specific glutamine-sensing metabolism. Glutamine is applied under clinical
      conditions as an oral, parenteral, or enteral supplement either as the single
      amino acid or in the form of glutamine-containing dipeptides for preventing
      mucositis/stomatitis and for preventing glutamine-deficiency in critically ill
      patients. Because of the high turnover rate of glutamine, even high amounts of
      glutamine up to a daily administration of 30 g can be given without any important
      side effects.

PMID- 18806120
TI  - Comparative aspects of tissue glutamine and proline metabolism.
AB  - The cellular metabolism of glutamine and proline are closely interrelated,
      because they can be interconverted with glutamate and ornithine via the
      mitochondrial pathway involving pyrroline-5-carboxylate (P5C). In adults,
      glutamine and proline are converted via P5C to citrulline in the gut, then
      citrulline is converted to arginine in the kidney. In neonates, arginine is a
      semiindispensable amino acid and is synthesized from proline completely in the
      gut; because of low P5C synthase activity, glutamine is not an important
      precursor for neonatal arginine synthesis. Thus, splanchnic metabolism of
      glutamine and proline is important, because both amino acids serve as key
      precursors for arginine synthesis with some developmental differences. Studies
      investigating splanchnic extraction demonstrate that about two-thirds of dietary
      glutamine and almost all dietary glutamate are extracted on first pass and the
      vast majority is oxidized in the gut. This capacity to extract glutamine and
      glutamate appears to be very large, so diets high in glutamine or glutamate
      probably have little impact on circulating concentrations and consequent
      potential toxicity. In contrast, it appears that very little proline is extracted
      by the gut and liver, at least in the neonate, which may result in
      hyperprolinemia and potential toxicity. Therefore, the upper limits of safe
      dietary intake for glutamine and proline, and other amino acids, appear to be
      substantially different depending on the extent of first-pass splanchnic
      extraction and irreversible catabolism.

PMID- 18806121
TI  - Clinical use of glutamine supplementation.
AB  - Endogenous production of glutamine may become insufficient during critical
      illness. The shortage of glutamine is reflected as a decrease in plasma
      concentration, which is a prognostic factor for poor outcome in sepsis. Because
      glutamine is a precursor for nucleotide synthesis, rapidly dividing cells are
      most likely to suffer from a shortage. Therefore, exogenous glutamine
      supplementation is necessary. In particular, when i.v. nutrition is given, extra
      glutamine supplementation becomes critical, because most present formulations for
      i.v. use do not contain any glutamine for technical reasons. The major part of
      endogenously produced glutamine comes from skeletal muscle. For patients staying
      a long time in the intensive care unit (ICU), the muscle mass decreases rapidly,
      which leaves a tissue of diminishing size to maintain the export of glutamine.
      The metabolic and nutritional adaptation in long-staying ICU patients is poorly
      studied and is one of the fields that needs more scientific evidence for clinical
      recommendations. To date, there is evidence to support the clinical use of
      glutamine supplementation in critically ill patients, in hematology patients, and
      in oncology patients. Strong evidence is presently available for i.v. glutamine
      supplementation to critically ill patients on parenteral nutrition. This must be
      regarded as the standard of care. For patients on enteral nutrition, more
      evidence is needed. To guide administration of glutamine, there are good
      arguments to use measurement of plasma glutamine concentration for guidance. This
      will give an indication for treatment as well as proper dosing. Most patients
      will have a normalized plasma glutamine concentration by adding 20-25 g/24 h.
      Furthermore, there are no reported adverse or negative effects attributable to
      glutamine supplementation.

PMID- 18806122
TI  - Dosing and efficacy of glutamine supplementation in human exercise and sport
      training.
AB  - Some athletes can have high intakes of l-glutamine because of their high energy
      and protein intakes and also because they consume protein supplements, protein
      hydrolysates, and free amino acids. Prolonged exercise and periods of heavy
      training are associated with a decrease in the plasma glutamine concentration and
      this has been suggested to be a potential cause of the exercise-induced immune
      impairment and increased susceptibility to infection in athletes. However,
      several recent glutamine feeding intervention studies indicate that although the
      plasma glutamine concentration can be kept constant during and after prolonged
      strenuous exercise, the glutamine supplementation does not prevent the
      postexercise changes in several aspects of immune function. Although glutamine is
      essential for lymphocyte proliferation, the plasma glutamine concentration does
      not fall sufficiently low after exercise to compromise the rate of proliferation.
      Acute intakes of glutamine of approximately 20-30 g seem to be without ill effect
      in healthy adult humans and no harm was reported in 1 study in which athletes
      consumed 28 g glutamine every day for 14 d. Doses of up to 0.65 g/kg body mass of
      glutamine (in solution or as a suspension) have been reported to be tolerated by
      patients and did not result in abnormal plasma ammonia levels. However, the
      suggested reasons for taking glutamine supplements (support for immune system,
      increased glycogen synthesis, anticatabolic effect) have received little support
      from well-controlled scientific studies in healthy, well-nourished humans.

PMID- 18806123
TI  - The 7th workshop on the assessment of adequate intake of dietary amino acids:
      summary of general discussion.
AB  - Extensive discussion sessions were held at the end of each of the 2 d of the
      workshop. Through the course of the workshop, it became clear that there were
      different opinions on how to use uncertainty factors to obtain upper levels of
      intake from no observed adverse effect levels of a particular nutrient and that
      the selection of an appropriate uncertainty factor would be rather arbitrary.
      Much of the discussion centered around the potential for using metabolic limits,
      expressed as the level of intake at which the major pathway of metabolism may
      approach saturation and at which the amino acid is metabolized by alternative
      pathways, as a measurable early or surrogate marker for amino acid excess and
      possible toxicity. After extensive discussion on various conditions that would
      need to be satisfied for metabolic limits to be used as markers of excessive
      intake of amino acids, there was a general consensus that methods such as
      measuring oxidation limits are an attractive approach that merit future
      investigation. It was noted that there are many data on the clinical use of
      glutamine, whereas data for proline are very scarce. There was recognition that
      regardless of the available data, there is regulatory pressure for setting upper
      levels of intake for amino acids and that much more data are required.

PMID- 18806124
TI  - Immune activation and IL-12 production during acute/early HIV infection in the
      absence and presence of highly active, antiretroviral therapy.
AB  - Suppressed IL-12 production and maladaptive immune activation, both of which are
      ameliorated by successful highly active antiretroviral therapy (HAART), are
      thought to play important roles in the immunopathogenesis of chronic HIV
      infection. Despite the important effects of the immunological and virological
      events of early HIV infection on subsequent disease progression, IL-12 production
      and immune activation in early infection remain under-defined. To quantify IL-12
      production and immune activation during acute/early HIV infection, in the
      presence and absence of HAART, we performed a prospective, longitudinal study of
      participants in the Baltimore site of the Acute Infection and Early Disease
      Research Program, with cross-sectional comparison to healthy control subjects.
      PBMC cytokine productive capacity and plasma immune activation markers [soluble
      CD8 (sCD8), sCD4, granzyme B, neopterin, beta2-microglobulin, sIL-2R, sTNFRI,
      sTNFRII, and IL-12p70] were quantified by ELISA. Notably, PBMC from patients with
      acute/early HIV infection exhibited in vivo IL-12p70 production along with
      increased, maximal in vitro IL-12 production. Further, despite evidence from
      plasma markers of generalized immune activation, no elevation in plasma levels of
      sCD4 was observed, suggesting relative blunting of in vivo CD4+ T cell activation
      from the beginning of HIV infection. Finally, despite successful virological
      responses to HAART, heightened in vivo CD8+ T cell activation, IL-12 production,
      and IFN activity were sustained for at least 6 months during primary HIV
      infection. These data underscore the need for comparative mechanistic analysis of
      the immunobiology of early and chronic HIV infection.

PMID- 18806125
TI  - Radiodefluorination of 3-fluoro-5-(2-(2-[18F](fluoromethyl)-thiazol-4
      yl)ethynyl)benzonitrile ([18F]SP203), a radioligand for imaging brain
      metabotropic glutamate subtype-5 receptors with positron emission tomography,
      occurs by glutathionylation in rat brain.
AB  - Metabotropic glutamate subtype-5 receptors (mGluR5) are implicated in several
      neuropsychiatric disorders. Positron emission tomography (PET) with a suitable
      radioligand may enable monitoring of regional brain mGluR5 density before and
      during treatments. We have developed a new radioligand, 3-fluoro-5-(2-(2
      [(18)F](fluoromethyl)thiazol-4-yl)ethynyl)benzonitrile ([(18)F]SP203), for
      imaging brain mGluR5 in monkey and human. In monkey, radioactivity was observed
      in bone, showing release of [(18)F]-fluoride ion from [(18)F]SP203. This
      defluorination was not inhibited by disulfiram, a potent inhibitor of CYP2E1. PET
      confirmed bone uptake of radioactivity and therefore defluorination of
      [(18)F]SP203 in rats. To understand the biochemical basis for defluorination, we
      administered [(18)F]SP203 plus SP203 in rats for ex vivo analysis of metabolites.
      Radio-high-performance liquid chromatography detected [(18)F]fluoride ion as a
      major radiometabolite in both brain extract and urine. Incubation of [(18)F]SP203
      with brain homogenate also generated this radiometabolite, whereas no metabolism
      was detected in whole blood in vitro. Liquid chromatography-mass spectrometry
      analysis of the brain extract detected m/z 548 and 404 ions, assignable to the [M
      + H](+) of S-glutathione (SP203Glu) and N-acetyl-S-l-cysteine (SP203Nac)
      conjugates of SP203, respectively. In urine, only the [M + H](+) of SP203Nac was
      detected. Mass spectrometry/mass spectrometry and multi-stage mass spectrometry
      analyses of each metabolite yielded product ions consistent with its proposed
      structure, including the former fluoromethyl group as the site of conjugation.
      Metabolite structures were confirmed by similar analyses of SP203Glu and
      SP203Nac, prepared by glutathione S-transferase reaction and chemical synthesis,
      respectively. Thus, glutathionylation at the 2-fluoromethyl group is responsible
      for the radiodefluorination of [(18)F]SP203 in rat. This study provides the first
      demonstration of glutathione-promoted radiodefluorination of a PET radioligand.

PMID- 18806126
TI  - Comparison of cigarette smoke-induced acute inflammation in multiple strains of
      mice and the effect of a matrix metalloproteinase inhibitor on these responses.
AB  - The activities of proteases in the lung, specifically matrix metalloproteinases
      (MMPs), have been implicated in driving the inflammation and lung destruction
      observed in smokers with chronic obstructive pulmonary disease. Here, our aims
      were to compare the acute response with cigarette smoke exposure (CSE) in four
      mouse strains to identify common and distinguishing features and to assess the
      effect of an MMP inhibitor on this response. To do this, we exposed mice (BALB/C,
      C57BL/6, A/J, or 129/Sv) to whole-body CSE (1 h/day) for 3 days. CSE induced dose
      and time-dependent increases in neutrophils and keratinocyte chemoattractant
      levels in the airways of all strains; however, the proportion of the neutrophilia
      differed among strains. In the two most contrasting strains, BALB/C and C57BL/6,
      we examined MMP gene expression and found only small changes apart from MMP-12,
      which was highly expressed in both strains. Both strains were then treated with a
      broad-spectrum MMP inhibitor, PKF242-484 [(2S,3R)-N(4)-((S)-2,2-dimethyl-1
      methylcarbamoyl-propyl)-N(1)-hydroxy-2-hydroxymethyl-3-(4-methoxy-phenyl)
      succinimide] (0.5-10 mg/kg) either orally or intranasally 1 h before and 5 h
      after CSE for 3 days. PKF242-484 dose-dependently reduced neutrophilia in BALB/C
      mice when dosed orally (p < 0.01) or intranasally (p < 0.01) but had no clear
      effect in C57BL/6 by either route. PKF242-484 reduced BAL macrophages when dosed
      intranasally (p < 0.05) but had no dose-dependent effect when dosed orally in
      both strains. These data suggest the inflammation induced by CSE is similar, but
      not identical, in different mouse strains. In addition, the ability of broad
      spectrum MMP inhibitors to inhibit smoke-induced acute neutrophil inflammation is
      strain-dependent, whereas its ability to limit macrophage infiltration may be
      route dependent.

PMID- 18806127
TI  - Radiology in Israel: what is happening?

PMID- 18806128
TI  - The written clinical diagnosis board examination: survey of program director and
      resident opinions.
AB  - OBJECTIVE: The purpose of our study was to assess the perceived value of the
      American Board of Radiology written clinical diagnosis board examination.
      MATERIALS AND METHODS: Two online surveys were distributed to diagnostic
      radiology programs approved by the Accreditation Council for Graduate Medical
      Education. Program directors were asked about the importance of the examination,
      and residents were asked about the importance and composition (proportion of
      repeated questions, known as recalls) of the examination and about preparation
      strategies. RESULTS: Most of the program directors (122 of 178, 69%) responded.
      Most of the respondents believed that the examination correlated with their
      assessment of residents' knowledge, that passing was indicative of a qualified
      radiologist, and that the examination should not be eliminated. Although most of
      the program directors believed preparation increased residents' knowledge, they
      also believed that preparation detracted from reading assignments. Opinion was
      divided whether the examination should be continued in its present form. The
      majority of the 171 resident respondents spent most of their time studying
      recalls, which they believed made up 40-60% of the examination. One half of the
      residents believed that preparing helped in mastering the body of radiology
      knowledge, although most believed that core material made up only 20-60% of the
      examination. A minority of the residents considered passing the examination
      indicative of a qualified radiologist. Opinion was divided on continuing the
      examination in its present form. CONCLUSION: Program directors and residents
      perceived value in the written clinical diagnosis board examination. The American
      Board of Radiology may need to reevaluate question content when restructuring the
      new examination.

PMID- 18806129
TI  - Imaging review of groin pain in elite athletes: an anatomic approach to imaging
      findings.
AB  - OBJECTIVE: Groin pain in elite athletes is a common yet challenging diagnostic
      and management dilemma for the sports clinician, accounting for a significant
      proportion of athletic injuries. It is often debilitating and, if severe enough,
      may compromise an athlete's career. Traditionally, groin pain has been poorly
      understood by radiologists. CONCLUSION: A major reason groin pain has been
      misunderstood is the complexity of the anatomy of this region, which this article
      discusses in detail in an effort to inform the reader.

PMID- 18806130
TI  - STIR sequence for depiction of degenerative changes in posterior stabilizing
      elements in patients with lower back pain.
AB  - OBJECTIVE: The aims of this study were to investigate whether degenerative
      posterior paraspinal changes are a cause of lower back pain and to determine the
      age- and sex-related distribution of these changes on MR images acquired with a
      STIR sequence. SUBJECTS AND METHODS: The lumbar MRI findings of 372 patients (141
      men, 231 women; mean age, 51.2 years) with nonradicular lower back pain and of
      249 healthy persons acting as controls (126 men, 123 women; mean age, 49.3 years)
      were analyzed. The sagittal STIR sequence was used for all MRI examinations.
      Presence of interspinous ligament edema, facet joint effusion, neocysts,
      paraspinal muscle edema, subcutaneous edema, disk herniation, and disk
      degeneration was evaluated, and the incidence of each finding was determined. All
      findings were grouped according to age and sex. Chi-square, Fisher's exact, and
      independent-samples Student's t tests and Spearman's rank correlation analysis
      were used for statistical analysis. RESULTS: The incidences of facet joint
      effusion, interspinous ligament edema, neocyst formation, and paraspinal muscle
      edema were found to be statistically significantly higher in patients with lower
      back pain than in controls. The incidences of intervertebral disk degeneration,
      disk herniation, and subcutaneous edema in persons with and those without lower
      back pain were similar. Intervertebral disk degeneration, disk herniation,
      subcutaneous edema, and muscle edema were found to increase with age in both
      persons with and those without symptoms. CONCLUSION: Degenerative changes in the
      posterior paraspinal structures were found in a higher percentage of subjects
      with lower back pain than in controls. Use of a STIR sequence with homogeneous
      fat suppression facilitates visualization of these changes.

PMID- 18806131
TI  - Role of diffusion-weighted MRI in the detection of early active sacroiliitis.
AB  - OBJECTIVE: This study proposed to evaluate the value of diffusion-weighted MRI
      (DWI) to detect active inflammatory changes in the sacroiliac joints of patients
      with early axial spondyloarthritis (also spelled spondylarthritis). SUBJECTS AND
      METHODS: Forty-two patients with chronic low back pain underwent clinical and MRI
      evaluation for axial spondyloarthritis or early ankylosing spondylitis. STIR,
      contrast-enhanced T1-weighted, fat-saturated T2-weighted, and diffusion-weighted
      (b values: 100, 600, 1,000 s/mm(2)) images were obtained. The presence of
      subchondral bone marrow edema, subchondral fatty marrow infiltration, or contrast
      enhancement in the sacroiliac joints or adjacent enthesitis sites was considered
      a marker for active inflammatory changes. All MRI sequences were evaluated for
      the presence of acute inflammatory changes and inter- and intrarater reliability
      of the sequences. Mean apparent diffusion coefficient (ADC) values of diffusion
      weighted images were calculated from normal and involved iliac and sacral bones
      of sacroiliac joints. RESULTS: ADC values measured from the lesions at b values
      of 1,000 and 600 s/mm(2) in patients with sacroiliitis (n = 13) were
      significantly higher than values measured from iliac and sacral bones in patients
      with low back pain of mechanical origin (n = 29). DWI showed sensitivity for
      detecting acute lesions in early sacroiliitis similar to that of T1-weighted
      gadolinium images (area under the curve, 0.843-0.971). Intra- and interrater
      reliability of DWI was acceptable. CONCLUSION: DWI is a sensitive, fast sequence
      and does not require a contrast agent, which makes it a good and cost-effective
      alternative for imaging sacroiliac joints. DWI also offers the possibility of
      quantifying diffusion coefficients of the lesions, which helps to discriminate
      between normal and involved subchondral bone.

PMID- 18806132
TI  - Pelvic bone complications after radiation therapy of uterine cervical cancer:
      evaluation with MRI.
AB  - OBJECTIVE: The purpose of this study was to assess the prevalence and
      distribution of radiation-induced insufficiency fractures and to investigate
      other bony complications of the female pelvis associated with radiation therapy
      using MR images. MATERIALS AND METHODS: Two radiologists retrospectively
      evaluated pelvic MR images of 510 patients (mean age, 54.7 years) who underwent
      pelvic irradiation for uterine cervical cancer for the presence and location of
      insufficiency fractures by consensus. We calculated the cumulative prevalence of
      pelvic insufficiency fractures on the basis of their results. In addition, we
      identified other associated bony complications of the female pelvis by reviewing
      the MR images. RESULTS: Insufficiency fractures were diagnosed in 100 patients;
      the 5-year cumulative prevalence was 45.2%. An insufficiency fracture was
      diagnosed a median of 16.9 months after radiation therapy. The fracture sites
      were the sacrum body and alae, medial side of the iliac bone, the roof of the
      acetabulum, superior rami of the pubic bone, femoral heads, and L5 vertebra.
      Sixty-one patients (61%) developed multiple fractures, and among them, 40 (40%)
      had bilateral symmetric lesions of the sacral alae. Other complications
      associated with the radiation therapy, as determined by evaluation of the MR
      images, were osteolysis and avascular necrosis of the femoral head. CONCLUSION:
      Radiation-induced pelvic insufficiency fractures are a frequent complication of
      radiation therapy for uterine cervical cancer. Osteolysis and avascular necrosis
      of the femoral head were also diagnosed using MRI after radiation therapy.

PMID- 18806133
TI  - MRI and CT of insufficiency fractures of the pelvis and the proximal femur.
AB  - OBJECTIVE: Pelvic and proximal femur insufficiency fractures are of increasing
      significance in our aging population, and cross-sectional imaging is challenging.
      The aims of this study were to compare the sensitivity of CT and MRI in detecting
      insufficiency fractures; to analyze the typical location, morphology, and
      combinations thereof in these fractures; to analyze imaging morphology; and to
      analyze associated clinical findings. MATERIALS AND METHODS: MRI studies obtained
      at 1.5 T were analyzed in 145 patients with pelvic insufficiency fractures. In 64
      of 145 patients, MRI and multidetector CT (MDCT) findings were compared. Imaging
      studies were analyzed by two radiologists; combined clinical history, findings
      from all imaging studies, and follow-up imaging studies served as the standard of
      reference. RESULTS: In the subgroup undergoing both imaging techniques, MRI
      detected 128 of 129 (99%) fractures in 63 of 64 (98%) subjects, whereas CT
      detected only 89 of 129 (69%) fractures in 34 of 64 (53%) subjects. In
      particular, fractures at the femoral head and acetabulum were better detected
      with MRI. In the complete population, two or more fractures were found in 70.3%
      (102/145) of patients, and 89.2% (33/37) of patients with pubic insufficiency
      fractures had concomitant fractures at other locations. In 63 of 145 (43.4%)
      patients, a previous malignancy was found; in only 93 of 145 (64.1%) patients,
      the leading symptom responsible for the MRI examination was pain. CONCLUSION:
      This study showed that MRI was substantially better than CT in detecting
      insufficiency fractures. In addition, two or more insufficiency fractures were
      frequently present, typical fracture combinations were found, and insufficiency
      fractures were frequently associated with malignant disease.

PMID- 18806134
TI  - MRI of acute meniscal injury associated with tibial plateau fractures:
      prevalence, type, and location.
AB  - OBJECTIVE: The purpose of this study was to evaluate the prevalence, type, and
      location of meniscal injuries, particularly to assess the prevalence of unstable
      meniscal tears in acute knee trauma with tibial plateau fractures. MATERIALS AND
      METHODS: A total of 78 menisci were evaluated in 39 patients who had undergone
      knee MDCT and MRI. Meniscal tears were classified as horizontal, vertical
      (subdivided into longitudinal and radial), flap, bucket-handle, or complex. The
      presence of meniscal contusion was documented. The anterior horn, body, and
      posterior horn were assessed separately for both menisci. Knee arthroscopy was
      performed on 28 patients. RESULTS: Of the 39 patients in the study, 24 had
      detectable abnormal menisci, for a total of 33 abnormal menisci (42%). Among the
      33 meniscal abnormalities were 11 longitudinal tears (33%), 17 contusions (52%),
      four flap tears (12%), six horizontal tears (18%), and six radial tears (18%).
      Among the 16 patients with meniscal tears (41% of the 39), 14 patients had an
      unstable tear. No significant correlation was found between degree of articular
      depression and site or morphologic features of the meniscal injury.
      Correspondingly, no statistical correlation was evident between normal menisci
      and degree of articular depression, nor was a significant correlation found
      between differing fracture groups and meniscal findings. CONCLUSION: A high
      percentage of patients (36%) with a tibial plateau fracture had an unstable
      meniscal tear. If a meniscal tear is detected preoperatively, meniscal surgery
      can be combined with fracture fixation, and reoperation can be avoided. A large
      number of meniscal contusions were found. Awareness of this abnormality can help
      radiologists increase specificity by avoiding false-positive findings of meniscal
      tear.

PMID- 18806135
TI  - Comparison of planar scintigraphy alone and with SPECT for the initial evaluation
      of femoral neck stress fracture.
AB  - OBJECTIVE: The objective of our study was to compare the accuracy of planar
      scintigraphy alone versus planar scintigraphy with SPECT for the initial
      evaluation of femoral neck stress fractures in a young military population.
      MATERIALS AND METHODS: We retrospectively identified 38 patients who had
      undergone planar scintigraphy and 33 patients who had undergone planar
      scintigraphy and SPECT before MRI of the hips over a 6-month period for
      evaluation of suspected femoral neck fracture. Data were analyzed regarding the
      sensitivity and specificity of bone scanning alone and with SPECT for detecting
      femoral neck stress fracture and grading fractures as low grade (grades I and II)
      or high grade (grades III and IV). RESULTS: Twelve fractures were identified in
      the group who underwent planar scintigraphy alone and 13 in the group who
      underwent planar scintigraphy with SPECT. The sensitivities of planar
      scintigraphy alone and with SPECT were 50% and 92.3%, respectively (p = 0.03).
      The accuracy of each technique for the detection of high-grade fractures was
      12.5% and 70%, respectively (p = 0.025). CONCLUSION: Planar scintigraphy with
      SPECT had a higher sensitivity and accuracy in assessing the grade of femoral
      neck stress fractures than planar scintigraphy alone. The results of this study
      suggest that SPECT should be performed with planar bone scintigraphy for the
      evaluation of patients with suspected femoral neck stress fractures.

PMID- 18806136
TI  - CT and MRI of spine and sacroiliac involvement in spondyloarthropathy.
AB  - OBJECTIVE: Spondyloarthropathies are rheumatoid diseases that predominantly
      affect the axial skeleton, causing pain, stiffness, and ankylosis. The aims of
      this article are to illustrate the different stages of the diseases from early
      inflammatory involvement to ankylosis using CT and MRI and to discuss the role of
      imaging in the management of affected patients. CONCLUSION: CT and MRI are the
      most sensitive techniques in the detection of axial involvement, permitting
      earlier diagnosis and optimized treatment.

PMID- 18806137
TI  - Usefulness of the abduction and external rotation views in shoulder MR
      arthrography.
AB  - OBJECTIVE: The purpose of this article is to illustrate the usefulness of the
      abduction and external rotation position in MR arthrography of the shoulder.
      CONCLUSION: The use of abduction and external rotation in shoulder MR
      arthrography can be a helpful tool that complements sequences that use
      conventional positions for characterizing a variety of abnormal conditions in the
      shoulder.

PMID- 18806138
TI  - MRI appearance of posterior cruciate ligament tears.
AB  - OBJECTIVE: There is little in the radiology literature regarding the MRI
      appearance of a torn posterior cruciate ligament (PCL). The purpose of this study
      was to describe the MRI appearance of surgically proven PCL tears and to
      emphasize previously unreported signs. CONCLUSION: The PCL is usually injured as
      the result of stretching deformation; on MRI, the ligament maintains continuity
      as a single structure with apparent thickening. On sagittal T2-weighted images,
      an anteroposterior diameter of 7 mm or more is highly suggestive of a torn PCL.
      Increased intrasubstance signal intensity in the PCL on proton-density images
      with lower signal intensity on T2-weighted images is another common feature.

PMID- 18806139
TI  - Accuracy of high-resolution CT in the diagnosis of diffuse lung disease: effect
      of predominance and distribution of findings.
AB  - OBJECTIVE: The purpose of this study was to determine whether the predominant
      findings at high-resolution CT influence the accuracy of diagnosis of diffuse
      lung disease. MATERIALS AND METHODS: The cases of 100 patients with diffuse lung
      disease who underwent high-resolution CT and tissue diagnosis were studied. Three
      thoracic radiologists reviewed high-resolution CT images blindly and
      independently for patterns of abnormality, listing their three main diagnoses and
      level of confidence in the first choice. The effect of the findings on accuracy
      was analyzed. RESULTS: For honeycombing, the accuracy of the main diagnosis was
      96.6%, 92.2%, and 92.3% for the three readers, and that of the three main
      diagnoses was 96.6%, 96.1%, and 92.3%. For cysts, the accuracy of the main
      diagnosis was 88.9%, 80%, and 81.8% and of the three main diagnoses was 100%,
      90%, and 90.9%. For bronchovascular thickening, the accuracy of the main
      diagnosis was 91.7%, 87.5%, and 90.9% and of the three main diagnoses was 91.7%,
      100%, and 90.9%. For ground-glass opacification (GGO), the accuracy of the main
      diagnosis was 75.5%, 55%, and 44.2% and of the three main diagnoses was 89.8%,
      75%, and 65.4%. Only combining honeycombing with GGO improved the accuracy of
      GGO. Anatomic craniocaudal distribution improved reader accuracy when GGO was
      predominantly present in the lower part of the lung. Interobserver agreement on
      the presence of major findings was a mean kappa value of 0.45 for honeycombing,
      0.74 for lung cysts, 0.63 for bronchovascular thickening, and 0.56 for GGO.
      Agreement for the craniocaudal distribution of major findings was a mean kappa
      value of 0.48 for honeycombing, 0.52 for bronchovascular thickening, and 0.32 for
      GGO. CONCLUSION: The predominant findings of honeycombing and bronchovascular
      thickening are associated with more than 90% accuracy in the first-choice
      diagnosis of diffuse lung disease; the finding of lung cysts has 80-89% accuracy.
      GGO as a predominant pattern had unreliable accuracy, but the accuracy improved
      when GGO was combined with either honeycombing or lower-lung distribution.

PMID- 18806140
TI  - Progression from near-normal to end-stage lungs in chronic interstitial pneumonia
      related to silica exposure: long-term CT observations.
AB  - OBJECTIVE: The objective of our study was to evaluate serial CT changes from
      normal or near-normal lungs to honeycomb lungs in dust-exposed patients who
      developed chronic interstitial pneumonia. MATERIALS AND METHODS: From the records
      of the national hospital for pneumoconiosis, we retrospectively identified
      patients with chronic interstitial pneumonia who were under surveillance between
      1986 and 2006. All patients occasionally underwent chest CT for evaluation of
      silicosis or exclusion of possible complications. Patients were included in this
      study only if the initial CT examination did not show obvious chronic
      interstitial pneumonia. Fourteen patients (all men; median age at initial CT, 58
      years) were identified as meeting the inclusion criterion. Two independent
      reviewers randomly reviewed the CT scans of the study patients to score the
      extent of ground-glass opacity, reticulation, and honeycombing; to provide a
      summation of all interstitial opacities (fibrosis score); and to assess
      coarseness. RESULTS: Autopsy findings were available for eight of the 14 patients
      and confirmed the usual interstitial pneumonia (UIP) pattern seen on CT. The
      median follow-up period was 15.4 years, and none of the patients experienced
      acute exacerbation. One hundred two CT scans were reviewed. The earliest CT
      abnormalities included faint ground-glass opacity limited to the lung bases (n =
      13) or only coarse reticular opacity (n = 1). In 13 patients, fibrosis and
      coarseness progressed linearly, whereas the other opacities did not. The annual
      increase of the fibrosis score and coarseness ranged from 0.306% to 4.633% and
      0.179 to 0.479, respectively. Honeycombing developed in all patients over a
      median period of 12.1 years (range, 3.7-19.1 years). CONCLUSION: The coarseness
      best represented the progression of chronic interstitial pneumonia in dust
      exposed patients. The earliest CT finding of a UIP pattern in dust-exposed
      patients was indistinguishable from other types of chronic interstitial
      pneumonia.

PMID- 18806141
TI  - MDCT evaluation of central airway and vascular complications of lung
      transplantation.
AB  - OBJECTIVE: The purpose of this article is to illustrate the spectrum of central
      airway and vascular complications in lung transplantation using MDCT, with an
      emphasis on the usefulness of advanced postprocessing techniques. CONCLUSION:
      MDCT is an invaluable tool in the diagnosis, evaluation, and posttreatment
      assessment of central airway and vascular complications in lung transplant
      recipients. Advanced postprocessing techniques provide complementary information
      that is visually accessible and anatomically meaningful for the clinician.

PMID- 18806142
TI  - Pulmonary nodules: detection, assessment, and CAD.
AB  - OBJECTIVE: The imaging of pulmonary nodules is an evolving and dynamic field. In
      this review, we discuss the detection and multitechnique characterization of
      pulmonary nodules, emphasizing the impact of technological advances on both
      noninvasive and invasive evaluation and surveillance. The potential contribution
      of MRI, evolving imaging-guided techniques, and computer applications are also
      discussed. CONCLUSION: Advances in MDCT and PET and the potential contribution of
      fast-imaging MRI sequences and computer applications should continue to improve
      our evaluation of the solitary pulmonary nodule.

PMID- 18806143
TI  - High-resolution CT findings of Mycobacterium avium-intracellulare complex
      pulmonary disease: correlation with pulmonary function test results.
AB  - OBJECTIVE: The purpose of our study was to analyze the high-resolution CT
      findings of the nodular bronchiectatic form of Mycobacterium avium-intracellulare
      complex (MAC) pulmonary disease and to correlate the extent of high-resolution CT
      findings with pulmonary function test (PFT) results. MATERIALS AND METHODS: From
      January 2005 through December 2005, we identified 47 patients (mean age, 58 +/-
      13 years; age range, 24-72 years; male-female ratio, 11:36) with the nodular
      bronchiectatic form of MAC pulmonary disease who underwent both high-resolution
      CT and PFTs. High-resolution CT findings were reviewed retrospectively in terms
      of the presence and extent of bronchiectasis, cellular or inflammatory
      bronchiolitis (centrilobular small nodules and tree-in-bud signs), cavity,
      nodule, and other findings. The extent of the abnormalities seen on high
      resolution CT was scored by modifying the cystic fibrosis scoring system proposed
      by Helbich and coworkers. The scores were correlated with PFT results using
      Spearman's correlation coefficient. RESULTS: On high-resolution CT, the three
      most frequently observed patterns of parenchymal abnormalities were, in
      decreasing order of frequency, cellular bronchiolitis (n = 47, 100%),
      bronchiectasis (n = 46, 98%), and consolidation (n = 27, 57%). The total CT score
      showed a significant correlation with the residual volume-total lung capacity
      (RV/TLC) ratio (r = 0.572, p < 0.001), forced expiratory volume in 1 second
      (FEV(1)) value (r = -0.426, p = 0.003), forced vital capacity (FVC) value (r = 
      0.360, p = 0.013), peak expiratory flow value (r = -0.352, p = 0.015), and peak
      expiratory flow between 25% and 75% of the forced vital capacity (FEF(25-75%)) (r
      = -0.289, p = 0.049). CONCLUSION: CT scoring of pulmonary abnormalities
      correlates with measures of functional impairment in patients with MAC pulmonary
      disease.

PMID- 18806144
TI  - Use of 3D adaptive raw-data filter in CT of the lung: effect on radiation dose
      reduction.
AB  - OBJECTIVE: The purpose of this study was to determine the effectiveness of a 3D
      adaptive raw-data filter in improving image quality and the role of the filter in
      radiation dose reduction in lung CT. MATERIALS AND METHODS: Fifty-eight chest CT
      examinations were performed with a 16-MDCT scanner. Two acquisitions were
      performed with different tube current-exposure time settings (50 and 150 mAs, 120
      kVp). Four series of lung images were prepared from two sets of raw data with and
      without application of a 3D adaptive filter (50 mAs, 50 mAs with filter, 150 mAs,
      150 mAs with filter). Three blinded readers using a 5-point scale from 1
      (nondiagnostic) to 5 (excellent) independently evaluated image quality in five
      lobes and the lingula. A set of images was considered acceptable when scores in
      all six regions were 3 (acceptable) or higher. The SD of attenuation was
      calculated in 24 regions of interest. RESULTS: The overall mean image quality
      scores were 3.09, 3.53, 4.02, and 4.38 for the 50 mAs, 50 mAs with filter, 150
      mAs, and 150 mAs with filter sets, respectively. Scores were significantly better
      with filter application (p < 0.001). A significant decrease in SD of attenuation
      was observed with filter application (p < 0.001). Among the respective series of
      images, 18, 52, 50, and 58 sets were judged acceptable with no significant
      difference in acceptability between images obtained at 50 mAs with a filter and
      at 150 mAs (p = 0.72). With filter application, the acceptability of 50-mAs
      images became comparable with that of 150-mAs images, making dose reduction to 50
      mAs practical. CONCLUSION: Use of a 3D adaptive raw-data filter improved the
      quality of lung images, making dose reduction to 50 mAs attainable with use of
      the filter.

PMID- 18806145
TI  - CT angiography findings of the left atrium and right ventricle in patients with
      massive pulmonary embolism.
AB  - OBJECTIVE: The purpose of this study was to show the imaging findings of the left
      atrium and right ventricle on CT angiography in patients with massive pulmonary
      embolism. CONCLUSION: Massive pulmonary embolism can cause abrupt acute pulmonary
      arterial hypertension, right ventricular dysfunction, and decrease in left
      ventricular preload. Patients with these findings on CT angiography can have a
      poorer prognosis than those without these imaging findings. Consequently,
      recognizing anatomic changes such as right ventricular dilation or septal bowing,
      decrease in size of left atrium and pulmonary veins (a manifestation of decreased
      pulmonary venous return) would be useful for risk stratification at the time of
      massive pulmonary embolism.

PMID- 18806146
TI  - Detection of occult colonic perforation before CT colonography after incomplete
      colonoscopy: perforation rate and use of a low-dose diagnostic scan before CO2
      insufflation.
AB  - OBJECTIVE: The purpose of this study was to obtain a low-dose CT scan before CT
      colonography to estimate the prevalence of occult colonic perforation among
      patients referred for same-day or next-day CT colonography after incomplete
      colonoscopy. MATERIALS AND METHODS: Two hundred sixty-two patients (74 men, 188
      women; mean age, 64 years; range, 21-92 years) consecutively referred for same
      day or next-day CT colonography after incomplete colonoscopy underwent low-dose
      diagnostic CT before rectal tube insertion and CO(2) insufflation. RESULTS:
      Perforation was found on the low-dose CT scans of two of the 262 patients (0.8%;
      95% CI, 0.1-2.7%). One of these patients had no symptoms; the other had mild
      abdominal discomfort at the time of CT. CONCLUSION: The rate of occult colonic
      perforation after incomplete colonoscopy may be significant. For patients
      referred for CT colonography after incomplete endoscopy, use of low-dose
      diagnostic CT before rectal tube insertion and insufflation is indicated.

PMID- 18806147
TI  - Duodenal abnormalities at MR small-bowel follow-through.
AB  - OBJECTIVE: The cross-sectional characterization of duodenal abnormalities is
      plagued with inadequacy, a reflection of the meandering course of this segment of
      the bowel. We consider the imaging appearance of such abnormalities at MRI small
      bowel follow-through, illustrating the typical manifestations of each
      pathologically confirmed condition. CONCLUSION: MRI small-bowel follow-through
      allows confident duodenal evaluation because of a combination of sufficient
      luminal distention and multiplanar versatility. Diseases of the duodenum may have
      a variety of manifestations at MRI small-bowel follow-through, the knowledge of
      which may aid in confident noninvasive patient diagnosis.

PMID- 18806148
TI  - Gasless abdomen in the adult: what does it mean?
AB  - OBJECTIVE: The objective of this article is to illustrate the causes of a gasless
      abdomen in an adult. CONCLUSION: The gasless abdomen in the adult is often
      interpreted as nonspecific, which does not provide useful information for the
      patient's physician. There are at least six causes of the gasless abdomen in the
      adult. A specific cause of the gasless abdomen can usually be made when the
      patient's history is known. The most serious cause of the gasless abdomen is
      small-bowel obstruction with or without ischemia.

PMID- 18806149
TI  - CT colonography: positioning order and intracolonic pressure.
AB  - OBJECTIVE: The purpose of this study was to prospectively evaluate the effect of
      the order of positions on sustained rectal pressure and factors affecting pain
      perceived by patients during air-insufflated CT colonography. SUBJECTS AND
      METHODS: Rectal pressure was measured in the supine and prone positions for CT
      colonography of 379 patients in two groups. One hundred seventy-seven patients
      underwent imaging supine and then prone, and 202 patients were prone and then
      supine. Insufflation and patient pain parameters were based on patient self
      report and investigator visualization of observable indicators. Colonic
      distention, residual feces or fluid, and diverticulosis were evaluated with a
      semiquantitative scoring system. Fisher's exact, Student's t, and chi-square
      tests as well as multivariate logistic regression analysis were performed.
      RESULTS: Pressure was higher in the prone than in the supine position in both
      groups (p < 0.001). The measured pressure in the initial position did not differ
      between groups (p = 0.88). Pressure increased from 38.3 to 40.07 mm Hg in the
      second position in the supine-first group and decreased from 38.3 to 32.25 mm Hg
      in the second position in the prone-first group (p < 0.001). The percentage of
      patients with pain in the second position was 40% in the supine-first group
      compared with 18% in the prone-first group (p < 0.003). Distention did not differ
      between the groups. Pain was associated with increased pressure and
      diverticulosis (p < 0.001) but not with retained feces or fluid. CONCLUSION:
      Sustained pressure in the air-insufflated colon was higher in the prone than in
      the supine position. Imaging in the prone position first results in a significant
      decrease in pressure in the latter phase and less pain. Pain was associated with
      pressure and diverticulosis.

PMID- 18806150
TI  - Influence of tagged fecal material on detectability of colorectal polyps at CT:
      phantom study.
AB  - OBJECTIVE: The purpose of this study was to determine the influence of tagged
      material on the minimal radiation dose needed to detect colorectal polyps at CT.
      MATERIALS AND METHODS: The study was conducted in two phases. In the first, three
      experienced observers determined the visibility of sessile polyps (6 mm) at five
      contrast levels (300, 480, 790, and 1,040 HU and air) and five tube charge levels
      (10, 14, 20, 28, and 40 mAs) in an anthropomorphic phantom. Each polyp was
      present in one of eight possible locations. The mean tube charge threshold for
      90% correct responses was determined for each contrast level. Blinded observers
      performed independent 2D readings. In the second phase of the study, three 150-cm
      virtual colons were evaluated at two contrast levels (300 and 480 HU) and at five
      tube charge levels between 20 and 80 mAs. The three colons contained 18 randomly
      located polyps. The mean tube charge threshold for 90% sensitivity was determined
      for each contrast level. RESULTS: In the first phase of the study, the estimated
      tube charge thresholds for 300, 480, and 790 HU were 24.0, 16.3, and 6.2 mAs. At
      1,040 HU and in air, all polyps were detected at the lowest tube charge setting
      (10 mAs). In the second phase, the tube charge thresholds for 90% sensitivity at
      300 and 480 HU were 70 and 35 mAs, respectively. CONCLUSION: If polyps are
      covered by fecal material, a considerably higher tube charge setting is needed
      for adequate visualization than is needed for polyps in a completely cleansed
      colon, especially when the density of the tagged residue is low.

PMID- 18806151
TI  - Therapeutic impact of CT of the appendix in a community hospital emergency
      department.
AB  - OBJECTIVE: The purpose of this study was to prospectively evaluate the
      therapeutic impact of CT of the appendix in a community hospital. SUBJECTS AND
      METHODS: For each of 100 consecutive adult patients who presented to a community
      hospital emergency department from August 2006 to November 2006 and underwent CT
      of the appendix, the proposed treatment plan and the likelihood of appendicitis
      were recorded before CT and were compared with the actual treatment after CT. The
      primary outcome assessed was change in patient management after CT. The
      percentage likelihood of appendicitis, whether patient disposition changed after
      CT, and the presence or absence of appendicitis were examined. The accuracy of CT
      was also calculated. RESULTS: The treatment plans of the emergency clinicians
      changed in 29 patients (29%). Appendicitis was ruled out on the basis of CT
      findings in 50% (9/18) of patients when appendicitis was considered probable and
      in 60% (3/5) when appendicitis was considered very likely. When appendicitis was
      considered unlikely, appendicitis was ruled out by CT in 100% (20/20) of
      patients. CT of the appendix was shown to have high sensitivity (94%),
      specificity (100%), positive predictive value (100%), negative predictive value
      (99%), and accuracy (99%). CONCLUSION: CT of the appendix had an important
      therapeutic impact on patients presenting to a community hospital emergency
      department. The data suggest that CT can be withheld in patients in whom
      emergency clinicians rate the likelihood of appendicitis as unlikely but that CT
      findings are often of benefit even when appendicitis is judged to be very likely.

PMID- 18806152
TI  - Noninvasive evaluation of active lower gastrointestinal bleeding: comparison
      between contrast-enhanced MDCT and 99mTc-labeled RBC scintigraphy.
AB  - OBJECTIVE: The purpose of our study was to compare contrast-enhanced MDCT and
      (99m)Tc-labeled RBC scanning for the evaluation of active lower gastrointestinal
      bleeding. SUBJECTS AND METHODS: Over 17 months, 55 patients (32 men, 23 women;
      age range, 21-92 years) were evaluated prospectively with contrast-enhanced MDCT
      using 100 mL of iopromide 300 mg I/mL. Technetium-99m-labeled RBC scans were
      obtained on 41 of 55 patients and select patients underwent angiography for
      attempted embolization. Each imaging technique was reviewed in a blinded fashion
      for sensitivity for detection of active bleeding as well as the active lower
      gastrointestinal bleeding location. RESULTS: Findings were positive on both
      examinations in eight patients and negative on both examinations in 20 patients.
      Findings were positive on contrast-enhanced MDCT and negative on (99m)Tc-labeled
      RBC in two patients; findings were negative on contrast-enhanced MDCT and
      positive on (99m)Tc-labeled RBC in 11 patients. Statistics showed significant
      disagreement, with simple agreement = 68.3%, kappa = 0.341, and p = 0.014.
      Sixteen of 60 (26.7%) contrast-enhanced MDCT scans were positive prospectively,
      with all accurately localizing the site of bleeding and identification of the
      underlying lesion in eight of 16 (50%). Nineteen of 41 (46.3%) (99m)Tc-labeled
      RBC scans were positive. Eighteen of 41 matched patients went on to angiography.
      In four of these 18 (22.2%) patients, the site of bleeding was confirmed by
      angiography, but in 14 of 18 (77.8%), the findings were negative. CONCLUSION:
      Contrast-enhanced MDCT and (99m)Tc-labeled RBC scanning show significant
      disagreement for evaluation of active lower gastrointestinal bleeding. Contrast
      enhanced MDCT appears effective for detection and localization in cases of active
      lower gastrointestinal bleeding in which hemorrhage is active at the time of CT.

PMID- 18806153
TI  - Diffusion-weighted imaging in the differential diagnosis of cystic lesions of the
      pancreas.
AB  - OBJECTIVE: The purpose of our study was to evaluate the value of diffusion
      weighted imaging (DWI) in the differential diagnosis of pancreatic cysts.
      SUBJECTS AND METHODS: Forty-two cysts (16 simple cysts, seven pseudocysts, five
      abscesses, three hydatid cysts, two serous cystadenomas, three mucinous
      cystadenomas, two mucinous cystadenocarcinomas, four cystic degenerated
      adenocarcinomas) were included in this prospective study. Single-shot spin-echo
      echo-planar DWI was performed with three b factors (0, 500, and 1,000 s/mm(2)),
      and apparent diffusion coefficients (ADCs) were calculated. On DWI, the signal
      intensity of the cysts was visually compared with the signal intensity of the
      pancreas parenchyma. For the quantitative evaluation, cyst-to-pancreas signal
      intensity ratios, ADC of the lesions, and cyst-to-pancreas ADC ratios were
      compared. RESULTS: On visual evaluation, all cystic lesions were hyperintense on
      DWI with b factors of 0 and 500 s/mm(2). On DWI with a b factor of 1,000 s/mm(2),
      all abscesses and hydatid and neoplastic cysts were hyperintense, whereas most of
      the simple and pseudocysts were isointense. Quantitatively, with b factors of 0
      and 500 s/mm(2), no statistical significance was achieved. With a b factor of
      1,000 s/mm(2), the cyst-to-pancreas signal intensity ratios of the abscesses and
      hydatid and neoplastic cysts were significantly higher than those of the simple
      cysts and pseudocysts. Setting the cutoff value of signal intensity ratio at 1.9,
      the cyst-to-pancreas signal intensity ratio had a sensitivity of 70% and a
      specificity of 90% for differentiating abscesses, hydatid cysts, and neoplastic
      cysts from simple cysts and pseudocysts. The ADC and the ADC ratios of the
      abscesses, hydatid cysts, and neoplastic cysts were significantly lower than
      those of the simple cysts and pseudocysts. CONCLUSION: DWI may help in the
      differential diagnosis of pancreatic cysts.

PMID- 18806154
TI  - Solitary necrotic nodules of the liver: cross-sectional imaging findings and
      follow-up in nine patients.
AB  - OBJECTIVE: The purpose of our study was to retrospectively evaluate the
      sonographic, CT, and MRI findings (number, diameter, lobar location, depth from
      the hepatic capsule, and appearance of lesions) in a series of nine patients with
      pathologically proven solitary necrotic nodules of the liver and the natural
      evolution at follow-up in four of the nine patients. CONCLUSION: Solitary
      necrotic nodules are usually small, solitary lesions, mainly located under the
      liver capsule of the right lobe. They are hypoechoic on sonography,
      hypoattenuating on CT, have low signal intensity on both T1- and T2-weighted MRI
      with lack of enhancement after IV contrast administration, and at follow-up have
      a tendency to show calcification and involution toward reduction in size.

PMID- 18806155
TI  - MRI safety update 2008: part 1, MRI contrast agents and nephrogenic systemic
      fibrosis.
AB  - OBJECTIVE: This article is the first part of a two-part series on MRI safety. In
      this article, part 1, the topic of MRI contrast agents and nephrogenic systemic
      fibrosis (NSF) is addressed. CONCLUSION: To prevent incidents and accidents
      associated with MRI, it is necessary to regularly revisit the safety topics that
      directly impact patient management especially with respect to the subjects that
      are "new" (e.g., MRI contrast agents and NSF), those that should be reassessed
      because of recent changes, topics that deserve emphasis because of controversy or
      confusion, and information that should be considered in light of new findings.

PMID- 18806156
TI  - MRI safety update 2008: part 2, screening patients for MRI.
AB  - OBJECTIVE: This article is the second part of a two-part series on MRI safety. In
      this article, part 2, the topic of screening patients for MRI procedures is
      addressed. CONCLUSION: To prevent incidents and accidents associated with MRI, it
      is necessary to regularly revisit the safety topics that directly impact patient
      management especially with respect to the subjects that are "new," those that
      should be reassessed because of recent changes, topics that deserve emphasis
      because of controversy or confusion, and information that should be considered in
      light of new findings.

PMID- 18806157
TI  - Nephrogenic systemic fibrosis and gadolinium: a perfect storm.

PMID- 18806158
TI  - MRI artifact reduction and quality improvement in the upper abdomen with
      PROPELLER and prospective acquisition correction (PACE) technique.
AB  - OBJECTIVE: The purpose of this study was to evaluate the effectiveness of the
      periodically rotated overlapping parallel lines with enhanced reconstruction
      (PROPELLER [BLADE in the MR systems from Siemens Medical Solutions]) with a
      respiratory compensation technique for motion correction, image noise reduction,
      improved sharpness of liver edge, and image quality of the upper abdomen.
      SUBJECTS AND METHODS: Twenty healthy adult volunteers with a mean age of 28 years
      (age range, 23-42 years) underwent upper abdominal MRI with a 1.5-T scanner. For
      each subject, fat-saturated T2-weighted turbo spin-echo (TSE) sequences with
      respiratory compensation (prospective acquisition correction [PACE]) were
      performed with and without the BLADE technique. Ghosting artifact, artifacts
      except ghosting artifact such as respiratory motion and bowel movement, sharpness
      of liver edge, image noise, and overall image quality were evaluated visually by
      three radiologists using a 5-point scale for qualitative analysis. The Wilcoxon's
      signed rank test was used to determine whether a significant difference existed
      between images with and without BLADE. A p value less than 0.05 was considered to
      be statistically significant. RESULTS: In the BLADE images, image artifacts,
      sharpness of liver edge, image noise, and overall image quality were
      significantly improved (p < 0.001). CONCLUSION: With the BLADE technique, T2
      weighted TSE images of the upper abdomen could provide reduced image artifacts
      including ghosting artifact and image noise and provide better image quality.

PMID- 18806159
TI  - Comparison of percutaneous and laparoscopic cryoablation for the treatment of
      solid renal masses.
AB  - OBJECTIVE: The goal of this study was to compare the outcome, complications, and
      charges of percutaneous renal cryoablation and laparoscopic cryoablation of solid
      renal masses. MATERIALS AND METHODS: A total of 30 percutaneous renal
      cryoablations (mean tumor size, 2.1 cm) in 30 patients (mean age, 67.0 years) and
      60 laparoscopic renal cryoablations (mean tumor size, 2.5 cm) in 46 patients
      (mean age, 67.4 years) were compared. The size of the tumor, procedural
      complications, hospital charges, length of hospital stay, and tumor follow-up
      parameters were recorded. Monitoring after ablation was performed every 3 months
      using contrast-enhanced MRI or CT. RESULTS: Both percutaneous cryoablation and
      laparoscopic cryoablation of solid renal masses had a high technical success rate
      (30/30 [100%] and 59/60 [98.3%]). There was no significant difference in the rate
      of residual disease (3/30 [10%] and 4/60 [6.7%], p = 0.68), and the secondary
      effectiveness rate is 100% for both groups to date. One renal mass treated using
      laparoscopic cryoablation had a local recurrence, but none of the masses treated
      using percutaneous cryoablation had a recurrence. The disease-specific survival
      is 100% in both groups with no significant difference in the mean follow-up time
      (14.5 vs 14.6 months, p = 1.0) or major complication rate (0/30 [0%] vs 3/60
      [5.0%], p = 0.55). For the treatment of solid renal masses, percutaneous
      cryoablation was associated with 40% lower hospital charges (mean, $14,175 vs
      $23,618, p < 0.00001) and a shorter hospital stay (mean +/- SD, 1.1 +/- 0.3 vs
      2.4 +/- 2.1 days; p < 0.0001) than laparoscopic cryoablation. CONCLUSION:
      Although certain tumors require laparoscopic intervention because of the location
      or size of the tumor, percutaneous renal cryoablation is safe and effective and
      is associated with lower charges when used for the treatment of small renal
      tumors.

PMID- 18806160
TI  - Safety and effectiveness of radiologic percutaneous gastrostomy and gastro
      jejunostomy in children with cardiac disease.
AB  - OBJECTIVE: The purpose of our study was to evaluate the safety and effectiveness
      of radiologic percutaneous gastrostomy and gastrojejunostomy for providing
      nutritional support in children with cardiac disease. MATERIALS AND METHODS:
      Retrospective chart review of 58 children with cardiac disease who underwent
      radiologic percutaneous gastrostomy from November 2001 to June 2005 was
      conducted. Patient data were collected until January 2007. The patients' weights
      were collected at the time of insertion and 6, 12, 18, and 24 months after
      insertion, and weight-for-age z-scores were calculated. RESULTS: The mean weight
      for-age z-score increased from -2.79 at the time of radiologic percutaneous
      gastrostomy insertion to -2.33 (p = 0.05) at 6 months after insertion, -1.89 (p =
      0.001) at 12 months, -1.65 (p = 0.0002) at 18 months, and -1.40 (p = 0.0004) at
      24 months. Repeated measures regression analysis showed a significant increase in
      weight-for-age z-score over time (p < 0.0001), with an estimated mean increase in
      weight-for-age z-score of 0.055 per month. No mortality was associated with the
      insertion or usage of radiologic percutaneous gastrostomy. Major complications
      included intestinal perforation (3.4%) and aspiration pneumonia (12.1%).
      CONCLUSION: Radiologic percutaneous gastrostomy is a safe method for providing
      long-term nutritional support in children with cardiac disease and is effective
      for improving growth and nutrition in this group of patients.

PMID- 18806161
TI  - Endovascular treatment for visceral vessel complication after branched graft
      replacement: initial results.
AB  - OBJECTIVE: The objective of our study was to retrospectively assess the safety
      and efficacy of endovascular treatment for branch stenosis or obstruction after
      branched graft replacement in patients with thoracoabdominal aortic aneurysm or
      aortic arch aneurysm. MATERIALS AND METHODS: Seven patients (all men; median age,
      62 years; age range, 19-79 years) who had undergone aortic surgery using branched
      grafts between March 2004 and January 2007 were treated. Diagnosis was
      established on dynamic contrast-enhanced CT or angiography. A self- or balloon
      expandable stent was placed after predilatation with a balloon catheter and, if
      necessary, thrombolysis was also performed. Stent patency was assessed on thin
      slice axial images obtained during the arterial phase on dynamic contrast
      enhanced CT. RESULTS: Seven lesions (one celiac artery, two left subclavian
      arteries, and four renal arteries) were treated. The time between the surgery and
      treatment was 0-3 days for patients with abdominal lesions and 20-41 days for
      those with thoracic lesions. Stent placement was successful in five of the seven
      patients. In one patient, insertion of the stent delivery system was
      unsuccessful; in the other patient, the stent was not completely expanded. The
      clinical symptoms and abnormal laboratory data improved in all patients with
      successful procedures. No restenosis was observed on imaging follow-up, with a
      median patency of 104 days (range, 5-1,218 days) during clinical follow-up
      (range, 37-1,218 days; median, 135 days). CONCLUSION: Endovascular repair can be
      an alternative treatment for visceral vessel complications of branched grafts,
      especially in obstructed but peripherally patent branches.

PMID- 18806162
TI  - A technique for MRI-guided transrectal deep pelvic abscess drainage.
AB  - OBJECTIVE: The purpose of this article is to introduce a technique for
      transrectal drainage of deep pelvic abscesses performed under interactive MRI
      guidance. CONCLUSION: A new method for triorthogonal image plane MRI guidance was
      developed and used to interactively monitor the puncture needle on continuously
      updated sets of adjustable three-plane images. The merits and limitations of the
      technique are highlighted and the patient population that is likely to benefit
      from this approach is suggested.

PMID- 18806163
TI  - Three-Dimensional CT venography of varicose veins of the lower extremity: image
      quality and comparison with doppler sonography.
AB  - OBJECTIVE: The purpose of this study was to verify the imaging quality of CT
      venography in the clinical evaluation of the lower extremity superficial venous
      system and to correlate the CT and duplex sonographic findings about varicose
      veins. SUBJECTS AND METHODS: One hundred consecutively registered patients with
      varicose veins underwent CT venography. The image quality of overall 3D volume
      rendering was rated, and the absolute attenuation of each component at the level
      of the knee was measured. Factors that affected visualization of varicose veins
      were identified. For comparison analysis, 50 of the 100 patients also underwent
      Doppler sonography, and saphenous vein size and morphologic features on CT were
      compared with the functional information from Doppler sonography. RESULTS: The
      overall quality of 3D volume-rendered images in the visualization of varicose
      veins was excellent in 76% of patients, fair in 21%, and poor in 3%. The entire
      length of the great saphenous vein (GSV) was visualized with CT venography in
      99.5% of 200 GSVs. The quality of 3D volume-rendered images was better when a
      thick subcutaneous layer, no skin changes, and no subcutaneous edema were
      present. Size of the GSV determined whether findings at CT venography and Doppler
      sonography correlated well, the linear regression coefficient being 0.72. At CT
      venography, the mean diameter of GSVs exhibiting insufficiency on duplex
      sonography was 7.0 mm, and the mean diameter of GSVs exhibiting competence on
      duplex sonography was 4.9 mm (p < 0.001). Prediction of GSV insufficiency with CT
      venography had a sensitivity of 98.2% and a specificity of 83.3%. CONCLUSION: CT
      venography has adequate image quality for evaluation of the venous system of the
      lower extremities.

PMID- 18806164
TI  - Anticoagulation and bleeding risk after core needle biopsy.
AB  - OBJECTIVE: The objective of our study was to compare the bleeding complication
      rates after core needle biopsy in patients receiving anticoagulation therapy and
      those who had not to assess the safety of performing core needle breast biopsy in
      anticoagulated patients. MATERIALS AND METHODS: Core needle biopsy was performed
      at 1,144 sites in 1,055 women from August 2004 to May 2007. A retrospective study
      of these cases was performed. The patient group was composed of 200 women (220
      biopsy sites) who were taking anticoagulant therapy daily (180 patients, aspirin;
      16 patients, warfarin; and four patients, Excedrin), and the control group was
      composed of 855 women (924 biopsy sites) who were not receiving daily
      anticoagulant therapy. Any adverse reactions after core needle biopsy, including
      the presence and size of bruises or lumps (hematomas), were recorded. RESULTS:
      There was a statistically significant difference (p = 0.035) in the percentage of
      bruises between patients receiving anticoagulation therapy and those who were
      not. Bruising occurred in 68 of the 200 (34%) women in the patient group
      (anticoagulated), whereas bruising occurred in 227 of the 855 (26.5%) women in
      the control group (nonanticoagulated). The differences were not statistically
      significant for hematoma formation (p = 0.274) or bruising with hematoma
      formation (p = 0.413). Hematoma occurred in 12 of the 200 (6%) anticoagulated
      patients versus 36 of the 855 (4.2%) patients in the control group. Patients
      reporting a bruise and lump (hematoma) numbered 10 of 200 (5%) for the
      anticoagulated group and 32 of 855 (3.7%) for the control group. CONCLUSION: No
      patients undergoing core needle biopsy reported any clinically important
      complications. The results of this study confirm that performing core needle
      biopsy in patients on anticoagulation therapy is safe.

PMID- 18806165
TI  - Complete excision of the MRI target lesion at MRI-guided vacuum-assisted biopsy
      of breast cancer.
AB  - OBJECTIVE: The purpose of our study was to determine the frequency of complete
      removal of the imaging target at MRI-guided vacuum-assisted biopsy of breast
      cancer and to assess the residual cancer rate at surgery in these lesions.
      MATERIALS AND METHODS: With the approval of our institutional review board,
      retrospective review was performed of 416 consecutive lesions that underwent MRI
      guided 9-gauge vacuum-assisted biopsy, of which 76 (18%) yielded cancer. Medical
      and pathology records were reviewed. RESULTS: Vacuum-assisted biopsy histology in
      76 cancers was ductal carcinoma in situ in 39 (51%) and invasive cancer in 37
      (49%). Median MRI lesion size in these 76 cancers was 1.2 cm (range, 0.4-8.0 cm).
      The median number of samples obtained was 12 (range, 6-24 samples). Among 76
      cancers, the MRI target was completely excised in 23 (30% [95% CI, 20-42%]),
      sampled in 52 (69% [57-79%]), and possibly missed in one (1% [0-7%]). Complete
      MRI target excision rather than sampling was significantly more likely in lesions
      < or = 1 cm than in lesions >1 cm (18/34 = 53% vs 5/41 = 12%; p < 0.001).
      Surgery, performed in 67 of 76 cancers, showed residual cancer in 55 (82% [71
      90%]). The residual cancer rate was significantly lower if the MRI target was
      completely excised rather than sampled (14/22 = 64% vs 40/44 = 91%; p < 0.02).
      CONCLUSION: Complete excision of the MRI target occurred in 30% of breast cancers
      diagnosed at MRI-guided vacuum-assisted biopsy. Among cancers in which the MRI
      target was percutaneously excised, surgery yielded residual cancer in 64%.
      Complete removal of the MRI target does not ensure complete histologic excision
      of the cancer.

PMID- 18806166
TI  - Preliminary in vivo validation of a dedicated breast MRI and sonographic
      coregistration imaging system.
AB  - OBJECTIVE: Sonographic correlation of breast MRI findings is often challenging.
      We present a preliminary in vivo feasibility study evaluating the degree of error
      of a new MRI-sonography coregistration system for showing MRI and sonographically
      visible breast lesions. CONCLUSION: In 10 patients with 13 lesions, the system
      was found to be an accurate means for targeting sonography to MRI of the same
      breast lesions.

PMID- 18806167
TI  - Feasibility of MRI of the fetal heart with balanced steady-state free precession
      sequence along fetal body and cardiac planes.
AB  - OBJECTIVE: The purpose of this study was to evaluate the feasibility of imaging
      the fetal heart with a balanced steady-state free precession MRI sequence along
      the body and cardiac axes after inadequate echocardiography. SUBJECTS AND
      METHODS: After technically inadequate echocardiography, MRI was performed on 20
      fetuses (mean gestational age, 24 weeks; range, 18-32 weeks) at risk of
      congenital heart disease. MRI was attempted along the three fetal body planes (n
      = 20) and cardiac axes (n = 3) without fetal sedation. The images were analyzed
      with an anatomic segmental approach. Each feature was classified as well
      visualized or poorly or not visualized. In each group, the Student's t test was
      used to assess the relation between visibility of fetal cardiac features and
      gestational age. RESULTS: Imaging was possible along the fetal body and cardiac
      axes. In the axial plane, a balanced four-chamber view was obtained in all
      fetuses, enabling evaluation of heart position, axis, chambers, and
      interventricular septum. The left and right ventricular outflow tracts were well
      visualized in 12 (60%) and nine (45%) of the fetuses, respectively; the three
      vessel view was obtained in 10 fetuses (50%). With the combination of sagittal
      and coronal views, both ventricular outflow tracts were assessed in all fetuses.
      The superior and inferior venae cavae were identified in all fetuses, and at
      least one pulmonary vein was visualized in 17 fetuses (85%). There were no
      statistically significant differences between gestational age and lack of
      visualization of a cardiac feature that was attributed to fetal motion.
      CONCLUSION: MRI of the fetal heart with a steady-state free precession sequence
      in multiple planes and image analysis with an anatomic segmental approach to
      congenital heart disease are possible in situations that limit echocardiography.

PMID- 18806168
TI  - Sonographically guided marker placement for confirmation of removal of
      mammographically occult lesions after localization.
AB  - OBJECTIVE: We evaluated the benefit of placing a marker under sonographic
      guidance at the time of localization to aid in identifying mammographically
      occult lesions within the specimen at the time of surgical excision and to
      evaluate margin status. MATERIALS AND METHODS: We reviewed 135 sonographically
      guided needle localizations performed on mammographically occult lesions. Imaging
      during the localization procedure, marker placement, and specimen radiographs
      were reviewed, and the findings were correlated with the histopathologic
      findings. RESULTS: Of the 135 mammographically occult lesions, 77 were localized
      without marker placement and 58 with marker placement. The 58 localizations with
      marker placement were for masses with a mean lesion size of 9 mm. Specimen
      radiography of these lesions showed a marker within the specimen in 56 cases
      (97%) and visualization of the lesion in only seven cases (12%). Specimen
      radiography of localizations without marker placement showed visualization of the
      lesion in 18 cases (23%). Of the 11 malignant lesions (19%) localized with marker
      placement, none had a positive inked margin, but five (46%) had close margins
      necessitating reexcision. Of the 26 malignant lesions (34%) localized without
      marker placement, two (8%) had a positive inked margin, and eight (31%) had close
      margins necessitating reexcision. CONCLUSION: At needle localization of breast
      lesions, marker placement under sonographic guidance is beneficial because it
      enables immediate confirmation of accurate surgical removal of the localized
      lesion at surgical excision. Use of marker placement, however, does not reduce
      the percentage of cases with close margins necessitating reexcision.

PMID- 18806169
TI  - Renal cell carcinoma: diagnosis, staging, and surveillance.
AB  - OBJECTIVE: This educational review focuses on the staging and radiologic
      evaluation of renal cell carcinoma. It includes discussion of the epidemiology,
      pathology, and therapeutic options of renal cell carcinoma and the implications
      for radiologic follow-up. CONCLUSION: The incidence of renal cell carcinoma has
      been increasing. Imaging plays a central role in its detection, staging, and
      treatment evaluation and follow-up.

PMID- 18806170
TI  - Follow-up after percutaneous radiofrequency ablation of renal cell carcinoma:
      contrast-enhanced sonography versus contrast-enhanced CT or MRI.
AB  - OBJECTIVE: The purpose of this study was to assess, with contrast-enhanced CT or
      MRI as the reference imaging technique, the diagnostic performance of low
      mechanical-index contrast-enhanced sonography in detecting local tumor
      progression after percutaneous radiofrequency ablation of renal tumors. MATERIALS
      AND METHODS: Twenty-nine patients with 30 renal tumors (18 men, 11 women; mean
      age, 73 years; range, 53-83 years) underwent percutaneous radiofrequency ablation
      at a single center between March 1998 and January 2007. The imaging follow-up
      schedule was both contrast-enhanced sonography and CT or MRI 4 months after
      completion of treatment and every 4 months for the first year. Thereafter, the
      follow-up schedule was contrast-enhanced sonography every 4 months with CT or MRI
      every 8 months. The chi-square test with Yates correction was used to evaluate
      positive and negative predictive values and accuracy. RESULTS: One patient was
      scheduled to undergo surgical resection, and another patient was lost to follow
      up. Twenty-seven patients with 28 renal tumors participated in follow-up. The
      concordance between contrast-enhanced sonographic and CT or MRI findings was 100%
      for 27 of 28 tumors (96.4%) that had a hypervascular pattern before treatment. In
      the case of the tumor that was hypovascular at imaging performed before
      percutaneous radiofrequency ablation, local tumor progression was missed at
      contrast-enhanced sonography. The sensitivity, specificity, positive predictive
      value, negative predictive value, and overall accuracy of contrast-enhanced
      sonography were 96.6%, 100%, 100%, 95.8%, and 98.1%. CONCLUSION: Contrast
      enhanced sonography is an effective alternative to CT and MRI in the follow-up of
      renal tumors managed with percutaneous radiofrequency ablation.

PMID- 18806171
TI  - Comparison of contrast-enhanced sonography with unenhanced sonography and
      contrast-enhanced CT in the diagnosis of malignancy in complex cystic renal
      masses.
AB  - OBJECTIVE: The objective of our study was to evaluate contrast-enhanced
      sonography in the diagnosis of malignancy in complex cystic renal masses.
      MATERIALS AND METHODS: We analyzed a series of 40 cystic renal masses (diameter,
      2-8 cm) with a complex pattern at contrast-enhanced CT in 40 consecutive subjects
      (18 men, 22 women; mean age +/- SD, 62 +/- 11 years). Each renal mass was scanned
      using sonography without contrast material and after IV injection of sulfur
      hexafluoride-filled microbubbles during the arterial (15-40 seconds) and venous
      (40-120 seconds from injection) phases. Two radiologists in consensus assessed
      onsite the enhancement patterns in the peripheral wall and intracystic septa and
      the evidence of solid endocystic components. Three blinded readers with 2, 6, and
      10 years of experience in renal imaging performed a retrospective off-site
      interpretation of unenhanced sonography, contrast-enhanced sonography, and CT
      images and made a benign or malignant diagnosis according to refer ence
      diagnostic criteria for contrast-enhanced sonography and to the Bosniak
      classification for CT. RESULTS: Final diagnoses comprised two multilocular cystic
      nephromas, two inflammatory and seven hemorrhagic cysts, and eight uncomplicated
      benign cysts and 21 cystic renal cell carcinomas. The overall diagnostic accuracy
      of contrast-enhanced sonography was better than unenhanced sonography and CT
      (contrast-enhanced sonography vs unenhanced sonography vs CT: reader 1, 83% vs
      30% vs 75%; reader 2, 83% vs 30% vs 63%; reader 3, 80% vs 30% vs 70%; p < 0.05,
      McNemar test). CONCLUSION: Contrast-enhanced sonography was found to be better
      than unenhanced sonography and CT in the diagnosis of malignancy in complex
      cystic renal masses.

PMID- 18806172
TI  - Role of endoluminal sonography in evaluation of obstruction of the ureteropelvic
      junction.
AB  - OBJECTIVE: The objective of this study was to evaluate the clinical feasibility
      of the use of 2D and 3D endoluminal sonography during endourologic procedures on
      patients with an obstructed ureteropelvic junction (UPJ). SUBJECTS AND METHODS:
      In 45 patients with an obstructed UPJ undergoing endoscopic procedures, a 6.2
      French catheter-based ultrasound probe (12.5 or 20 MHz) was inserted under
      endoscopic guidance into the upper urinary tract for acquisition of 2D images for
      evaluation of UPJ structures and construction of 3D volume images with a computer
      workstation. The role of 3D in addition to 2D imaging for identification of
      abnormalities at the UPJ was evaluated. RESULTS: Both 2D and 3D images depicted
      crossing vessels at the UPJ in 24 of 43 patients (55.8%) and a ureteral septum in
      14 of 43 patients (32.6%), and endoscopic incisions were successfully made with
      sonographic guidance. The anatomic structures of the UPJ associated with
      abnormalities (e.g., crossing vessels, septum, calculi, tumors, and strictures)
      were appreciated and evaluated more fully on 3D than on 2D images. The
      endoluminal sonographic findings helped rule out or modify the interventional
      procedure (endopyelotomy or balloon ureteroplasty) in the cases of eight of 43
      patients (18.6%). CONCLUSION: Three-dimensional endoluminal sonography clearly
      displays diagnostic information that complements 2D imaging findings and enhances
      the assessment of normal and abnormal structures at the UPJ for endourologic
      surgery.

PMID- 18806173
TI  - Inflammatory pseudotumor (myoblastic tumor) of the genitourinary tract.
AB  - OBJECTIVE: The purpose of this article is to describe imaging features of the
      following genitourinary tract locations that can involve inflammatory
      pseudotumor: kidney, adrenal gland, retroperitoneum or pelvis, bladder, and other
      rare locations. CONCLUSION: Although definite radiologic differentiation from
      malignancy is not clearly possible, we suggest that familiarity with the
      manifestations of inflammatory pseudotumor can help avoid unnecessary radical
      surgery before histopathologic proof of malignancy is obtained.

PMID- 18806174
TI  - Optimization of perfusion imaging for acute cerebral ischemia: review of recent
      clinical trials and recommendations for future studies.
AB  - OBJECTIVE: The use of thrombolytic agents and other forms of reperfusion therapy
      has provided a means to reverse ischemia and minimize the size of infarctions.
      The purpose of this review is to examine various clinical trials of reperfusion
      agents and address key imaging issues. CONCLUSION: Advanced MRI and CT play a
      growing role in selection of patients for therapy. Numerous clinical trials have
      shed light on the efficacy of various reperfusion therapies; disparities in trial
      design have also left unanswered questions.

PMID- 18806175
TI  - Fundamental similarities between tort and administrative systems for managing
      health care accidents.

PMID- 18806176
TI  - 'They're more like ordinary stroppy British women': attitudes and expectations of
      maternity care professionals to UK-born ethnic minority women.
AB  - OBJECTIVE: To explore the attitudes and expectations of maternity care
      professionals to UK-born ethnic minority mothers. METHODS: Qualitative in-depth
      interviews with 30 professionals from eight NHS maternity units in England that
      provide services for large proportions of women of black Caribbean, black
      African, Indian, Pakistani and Irish descent. RESULTS: All the professionals
      reported providing care to both UK-born and migrant mothers from ethnic
      minorities. Most of them felt that they could differentiate between UK-born and
      migrant mothers based mainly on language fluency and accent. 'Westernized dress'
      and 'freedom' were also cited as indicators. Overall, professionals found it
      easier to provide services to UK-born mothers and felt that their needs were more
      like those of white English mothers than those of migrant mothers. UK-born
      mothers were generally thought to be assertive and expressive, and in control of
      care-related decision-making whereas some South Asian Muslim women were thought
      to be constrained by family influences. Preconceived ideas about ethnic minority
      mothers' tolerance of pain in labour, use of pharmacological pain relief measures
      and mode of delivery were recurring themes. Women's education and social class
      were felt to be major influences on the uptake of maternity care, regardless of
      ethnicity. CONCLUSIONS: Professionals appeared to equate the needs of UK-born
      ethnic minority women with those of white English women. Overall, this has
      positive implications for care provision. Despite this, specific behavioural
      expectations and unconscious stereotypical views were evident and have the
      potential to affect clinical practice.

PMID- 18806177
TI  - Increasing appropriateness of hospital admissions in the Emilia-Romagna region of
      Italy.
AB  - OBJECTIVES: The Emilia-Romagna region of Italy has reduced the number of
      available hospital beds and introduced financial incentives to curb hospital use.
      The goal of this study was to assess the impact of these policies on changes over
      time in the number of acute hospital admissions classified in diagnosis related
      groups (DRGs) that could be treated safely and effectively in alternative, less
      costly settings. METHODS: The assessment of the appropriate site of care was
      based on analysis of hospital discharge data for all hospitals for the selected
      diagnosis related groups in the Emilia-Romagna region for 2001 to 2005. The
      necessity for acute hospital admission was based on the severity of a patient's
      principal diagnosis, co-morbid diseases and, for surgical admissions, procedure
      performed. RESULTS: From 2001 to 2005, potentially inappropriate medical
      admissions of more than one day decreased from 20,076 to 11,580, a 42% decrease.
      Inappropriate admissions decreased in both public and private hospitals but there
      remained a higher rate of inappropriate admissions to private hospitals.
      Potentially inappropriate medical admissions accounted for 128,319 bed-days in
      2001 and 68,968 bed-days in 2005, a reduction of 59,351 bed-days. Potentially
      inappropriate surgical admissions decreased from 7383 in 2001 to 4349 in 2005, a
      41% decrease. Bed-days consumed by inappropriate surgical admissions decreased
      from 23,181 in 2001 to 13,660 in 2005. CONCLUSIONS: The Emilia-Romagna region has
      succeeded in reducing the use of acute hospital beds for patients in selected
      diagnosis related groups. However, there are still substantial numbers of
      admissions that could potentially be treated in less costly settings.

PMID- 18806178
TI  - Policy-makers' attitudes to decision support models for coronary heart disease: a
      qualitative study.
AB  - OBJECTIVES: To explore attitudes to the use of models for coronary heart disease
      to support decision-making for policy and service planning. METHODS: Qualitative
      study using semi-structured interviews with 33 policy- and decision-makers
      purposively sampled from the UK National Health Service (NHS) (national, regional
      and local levels), academia and voluntary organizations. Interviews were
      transcribed, coded and emergent themes identified using framework analysis aided
      by NVivo software. RESULTS: Policy-makers and planners were generally
      enthusiastic about models to assist in decision-making through: predicting
      trends; assessing the effect of interventions on health inequalities; quantifying
      the impact of population level and targeted interventions, and facilitating
      economic evaluation. The perceived advantages of using models included: more
      rational commissioning; the facility for scenario testing; advocacy for
      population level interventions and off-the-shelf synthesis to aid real time
      decision-making. However, although participants were aware of models to support
      decision-making, these were not being used routinely. Some participants felt that
      models oversimplify complex situations and that there is a lack of shared
      understanding as to how models work. Factors that increase confidence in decision
      support models included: rigorous validation and peer review, the availability of
      user-support and increased transparency. CONCLUSION: Policy-makers and planners
      were generally enthusiastic about the use of models to support decision-making,
      illustrating the potential uses for models and the factors that improve
      confidence in them. However, existing models are often not being used in
      practice. So new models that are fit for practice need to be developed.

PMID- 18806179
TI  - Stakeholders' views of UK nurse and pharmacist supplementary prescribing.
AB  - OBJECTIVES: Supplementary prescribing (SP) by pharmacists and nurses in the UK
      represents a unique approach to improving patients' access to medicines and
      better utilizing health care professionals' skills. Study aims were to explore
      the views of stakeholders involved in SP policy, training and practice, focusing
      upon issues such as SP benefits, facilitators, challenges, safety and costs,
      thereby informing future practice and policy. METHOD: Qualitative, semi
      structured interviews were conducted with 43 purposively sampled UK stakeholders,
      including pharmacist and nurse supplementary prescribers, doctors, patient groups
      representatives, academics and policy developers. Analysis of transcribed
      interviews was undertaken using a process of constant comparison and framework
      analysis, with coding of emergent themes. RESULTS: Stakeholders generally viewed
      SP positively and perceived benefits in terms of improved access to medicines and
      fewer delays, along with a range of facilitators and barriers to the
      implementation of this form of non-medical prescribing. Stakeholders' views on
      the economic impact of SP varied, but safety concerns were not considered
      significant. Future challenges and implications for policy included SP being
      potentially superseded by independent nurse and pharmacist prescribing, and the
      need to improve awareness of SP. Several potential tensions emerged including
      nurses' versus pharmacists' existing skills and training needs, supplementary
      versus independent prescribing, SP theory versus practice and prescribers versus
      non-prescribing peers. CONCLUSION: SP appeared to be broadly welcomed by
      stakeholders and was perceived to offer patient benefits. Several years after its
      introduction in the UK, stakeholders still perceived several implementation
      barriers and challenges and these, together with various tensions identified,
      might affect the success of supplementary and other forms of non-medical
      prescribing.

PMID- 18806180
TI  - The impact of income on private patients' access to GP services in Ireland.
AB  - OBJECTIVES: To examine the extent to which proximity to the income threshold for
      free GP care results in significant differences in GP visiting. Approximately 30%
      of the Irish population receives free GP care (medical card patients), while the
      remaining 70% pays in full (private patients). Medical card eligibility exerts a
      significant influence on GP visiting, but how do GP visiting rates differ among
      private patients on differing incomes, and has the differential in visiting among
      private patients changed over time? METHODS: Using micro-data from three
      nationally representative surveys of the Irish population undertaken in 1987,
      1995 and 2001, multivariate models of GP utilization are estimated. RESULTS:
      There is little evidence that proximity to the income threshold results in
      significant differences in GP visiting. The most significant difference is
      between medical card and private patients, rather than between private patients
      on differing incomes. There is also little evidence that the differential in GP
      visiting between private patients on different incomes changed over time.
      CONCLUSIONS: While recent commentary has focused on the plight of individuals
      just above the income threshold for free GP care, these results suggest that the
      key difference in GP visiting is between those with, and without, eligibility for
      free care. If private patients are prevented from accessing GP care due to cost,
      this is as much an issue for those at the top of the income distribution as for
      those at the bottom.

PMID- 18806181
TI  - Health care professionals' views of implementing a policy of open disclosure of
      errors.
AB  - OBJECTIVES: To understand the views of doctors, nurses, allied health
      professionals and health managers of open disclosure of medical errors. METHODS:
      Semi-structured interviews were conducted with 131 health professionals to
      understand their experiences of implementing open disclosure in 21 providers in
      Australia. RESULTS: Health professionals are positive about open disclosure and
      are applying the model to patient-clinician communication encounters more
      generally. Workforce and systems competencies enable clinicians and health
      service managers to implement open disclosure principles and practices, although
      a propensity to hide errors, wavering commitment and to exacerbate the problem
      inhibits implementation as policy intends. The gap between policy objectives and
      their implementation limits the benefits to health professionals. CONCLUSION:
      Health services must develop organizing capabilities if open disclosure is to be
      implemented as intended. Activities should identify and address factors that
      impede implementation and enable workforce and system competencies to develop.
      These activities will allow health services to adapt central open disclosure
      policy to local conditions and to embed its principles and practices organization
      wide.

PMID- 18806182
TI  - Moving specialist care into the community: an initial evaluation.
AB  - OBJECTIVES: To assess the likely impact on patients and local health economies of
      shifting specialist care from hospitals to the community in 30 demonstration
      sites in England. METHODS: The evaluation comprised: interviews with service
      providers at 30 sites, supplemented by interviews with commissioners, GPs and
      hospital doctors at 12 sites; economic case studies in six sites; and patient
      surveys at 30 sites plus at nine conventional outpatient services. Outcomes
      comprised: staff views of service organization and development, impact on primary
      and secondary care, and benefits for patients; cost per consultation and cost per
      patient in new services compared to estimates of the price of services if
      undertaken by hospitals; patients' views of waiting time, access, quality
      (technical and interpersonal), coordination and satisfaction. RESULTS: New
      services required high initial investment in staff, premises and equipment, and
      the support of hospital consultants. Most new services were added to existing
      hospital services so expanded capacity. Patient reported waiting times (6.7
      versus 10.1 weeks; p = 0.001); technical quality of care (96.2 versus 94.5; p <
      0.001), overall satisfaction (88.2 versus 85.4; p = 0.04); and access (72.2
      versus 65.8; p = 0.001) were significantly better for new compared to
      conventional services but there was no significant difference in coordination or
      interpersonal quality of care. Some service providers expressed concerns about
      service quality. New services dealt with less complex conditions and undercut the
      price tariff applied to hospitals thus providing a cost saving to commissioners.
      There was some concern that expansion of new services might destabilize
      hospitals. CONCLUSIONS: Moving specialist care into the community can improve
      patient access, particularly when new services are added to existing hospital
      services. Wider impacts on health care quality, capacity and cost merit closer
      scrutiny before rollout.

PMID- 18806183
TI  - Factors contributing to nursing leadership: a systematic review.
AB  - OBJECTIVES: Leadership practices of health care managers can positively or
      negatively influence outcomes for organizations, providers and, ultimately,
      patients. Understanding the factors that contribute to nursing leadership is
      fundamental to ensuring a future supply of nursing leaders who can positively
      influence outcomes for health care providers and patients. The purpose of this
      study was to systematically review the multidisciplinary literature to examine
      the factors that contribute to nursing leadership and the effectiveness of
      educational interventions in developing leadership behaviours among nurses.
      METHODS: The search strategy began with 10 electronic databases (e.g. CINAHL,
      Medline). Published quantitative studies were included that examined the factors
      that contribute to leadership or the development of leadership behaviours in
      nurse leaders. Quality assessments, data extraction and analysis were completed
      on all included studies. RESULTS: A total of 27,717 titles/abstracts were
      screened resulting in 26 included manuscripts reporting on 24 studies. Twenty
      leadership factors were examined and categorized into four groups - behaviours
      and practices of individual leaders, traits and characteristics of individual
      leaders, influences of context and practice settings, and leader participation in
      educational activities. Specific behaviours and practices of individual leaders,
      such as taking on or practising leadership styles, skills and roles, were
      reported as significantly influencing leadership in eight studies. Traits and
      characteristics of individual leaders were examined in six studies with previous
      leadership experience (three studies) and education levels (two of three studies)
      having positive effects on observed leadership. Context and practice settings had
      a moderate influence on leadership effectiveness (three of five studies). Nine
      studies that examined participation in leadership development programs all
      reported significant positive influences on observed leadership. CONCLUSION:
      These findings suggest that leadership can be developed through specific
      educational activities, and by modelling and practising leadership competencies.
      However, the relatively weak study designs provide limited evidence for specific
      factors that could increase the effectiveness of current nursing leadership or
      guide the identification of future nurse leaders. Robust theory and research on
      interventions to develop and promote viable nursing leadership for the future are
      needed to achieve the goal of developing healthy work environments for health
      care providers and optimizing care for patients.

PMID- 18806184
TI  - Everything you wanted to know about anxiety but were afraid to ask.

PMID- 18806185
TI  - What leads to better health care innovation? Arguments for an integrated policy
      oriented research agenda.
AB  - This essay is based on the recognition that the current 'downstream' health
      services research and policy approach to innovation misses the mark on one
      crucial point. It has not addressed how to promote the design of innovations that
      are likely to be more valuable than others. Re-visiting the ways in which health
      services research could inform innovation processes, this paper suggests that
      three attributes make innovations especially compelling from a health care system
      perspective: relevance; usability; and sustainability. These could be used as a
      starting point for outlining a policy-oriented research agenda that could bridge
      upstream design processes, and downstream needs and priorities. Given the pace at
      which innovations come about and the complexity of health care systems, we
      believe that both research and policy should be able to contribute significantly
      to the shaping of socially valuable technological change in health care.
      Recognizing that such a long-term goal cannot be reached through a linear,
      rationalistic process, our paper offers preliminary arguments to start to
      reconcile the health policy and innovation agendas.

PMID- 18806186
TI  - Why does health services research seem so hard to fund?

PMID- 18806187
TI  - Research capacity development and training.
AB  - The HSRC was awarded a large core grant specifically for research capacity
      development and training, with the aim of facilitating future high quality HSR in
      the UK. This was used to pursue three main areas of activity. First, the
      provision of small grants to facilitate the development of new work, help create
      new, multidisciplinary groupings and support junior researchers. Of the various
      schemes discussed, the research initiation grants (max pound6000) and workshop
      awards (max pound3000) appear to have been particularly valuable. Second, appoint
      cohorts of PhD students to pursue four-year training programmes (rather than the
      traditional three years), during which they received individualized research
      training and development opportunities with an emphasis on both multidisciplinary
      HSR training and generic skills training, as well as pursuing their own research
      projects. Third, improving research training opportunities by developing networks
      for research staff at various stages in their careers and organizing workshops
      and courses in specialist HSR subjects, and for generic skills training. The
      premature closure of the HSRC prevented us from fully evaluating these
      initiatives and, arguably, their real value will not be apparent for some years.
      However, we believe that the programme was successful and that it went some way
      to helping us break out from the traditional, entrenched approaches to research
      training, and to helping us think of research capacity development as being as
      important as doing the research itself. But much more remains to be done.

PMID- 18806188
TI  - Multiparameter evidence synthesis in epidemiology and medical decision-making.
AB  - Meta-analysis has been well-established for many years, but has been largely
      confined to pooling evidence on pair-wise contrasts. Broader forms of synthesis
      have also been described, apparently re-invented in disparate fields, each time
      taking different computational approaches. The potential value of Bayesian
      estimation of a joint posterior parameter distribution and simultaneously
      sampling from it for decision analysis has also been appreciated. However,
      applications have been relatively few in number, sometimes stylized, and
      presented mainly to a statistical methods audience. As a result, the potential
      for multiparameter evidence synthesis in both epidemiology and health technology
      assessment has remained largely unrecognized. The advent of flexible software for
      Bayesian Markov chain Monte Carlo in the shape of WinBUGS has the made these
      earlier strands of work more widely available. Researchers can now carry out
      synthesis at a realistic level of complexity. The Bristol programme has not only
      contributed to a growing body of literature on how to synthesize different
      evidence structures, but also on how to check the consistency of multiple
      information sources and how to use the resulting models to prioritize future
      research.

PMID- 18806189
TI  - Decision analysis for resource allocation in health care.
AB  - This paper addresses the use of economic evaluation to inform resource allocation
      decisions within health care systems about which interventions to reimburse and
      whether additional research should be funded. A social decision-making view of
      economic evaluation, that is to maximize health gains subject to an exogenous
      budget constraint, is adopted. A brief overview of the components of an economic
      evaluation is presented. Particular attention is paid to how uncertainty is
      inherent to decisions about resource allocation, the consequences of that
      uncertainty and how it can be incorporated informatively into economic
      evaluation. A Bayesian approach to uncertainty is used as it meets the needs of
      social decision-making, allowing analysts to quantify the probability that an
      intervention is cost-effective given the available evidence and to quantify the
      expected value of further research. The discussion covers methods to represent
      parameter and structural uncertainty and considers the role of formal elicitation
      of expert judgements. The association between decisions to approve interventions
      for reimbursement and decisions about future research funding, and how value of
      information analysis can be used to formalize this link, is explained. Recent
      developments in the UK highlight the evolving policy environment for economic
      evaluation, such as the Cooksey report on the funding of UK health research, the
      review of the Pharmaceutical Price Regulation Scheme by the Office of Fair
      Trading and the update of the methodological guidelines issued by the National
      Institute for Health and Clinical Excellence. The paper concludes by describing
      ongoing methodological work designed to meet the challenges of undertaking
      decision analysis for resource allocation in health care.

PMID- 18806190
TI  - Investigating Choice Experiments for Preferences of Older People (ICEPOP):
      evaluative spaces in health economics.
AB  - This paper deals with three concerns about the evaluative framework that is
      currently dominant within health economics. These concerns are: that the
      evaluative framework is concerned entirely with health; that the evaluative
      framework has an individualistic focus on patients alone; and that the methods
      used to estimate 'health' within the current evaluative framework could be
      improved both in terms of the generation of descriptive systems and in using
      valuation methods that rely less on people's ability to express their preferences
      on a cardinal scale. In exploring these issues the Investigating Choice
      Experiments for Preferences of Older People (ICEPOP) programme has explicitly
      focused on both the topic of older people and the methods of discrete choice
      experiments. A capability index has been developed and attributes for an economic
      measure of end-of-life care are currently being generated, providing the
      possibility of extending the evaluative framework beyond health alone. A measure
      of carer's experience and a framework for extending measurement in end-of-life
      care to loved ones are both also in development, thus extending the evaluative
      framework beyond the patient alone. Rigorous qualitative methods employing an
      iterative approach have been developed for use in constructing attributes, and
      best-worst scaling has been utilized to reduce task complexity and provide
      insights into heterogeneity. There are a number of avenues for further research
      in all these areas, but in particular there is need for greater attention to be
      paid to the theory underlying the evaluative framework within health economics.

PMID- 18806191
TI  - Locomotor disability: meaning, causes and effects of interventions.
AB  - This paper provides a synopsis of a long-term programme of MRC-funded work on
      locomotor disability in older people. Specifically it describes the meaning and
      experience of disability, examines the risk factors for disability and
      systematically reviews the evidence from randomized trials of complex
      interventions for disability. We undertook a national prospective study of a
      representative sample of 999 people aged 65 years or more plus in-depth
      interviews with a small subsample and a selected sample obtained from hospital
      sources. Secondary analysis of several large prospective studies was carried out
      and a systematic review and meta-analysis of published randomized controlled
      trials of the effects of complex interventions for disability. Very few
      participants subscribed to the constructs of longstanding illness, disability or
      infirmity that surveys often use. A wide range of social and psychological
      factors, independently of chronic diseases, were strongly associated with
      disability. People with greater functional reserve capacity and those with
      greater self-efficacy were generally less likely to suffer from catastrophic
      decline in ability and had better quality of life in the face of disability. In
      reviewing 89 trials (over 97,000 participants) of complex interventions for
      disability, evidence of benefits was found although no relationship with
      intensity of intervention was apparent. Our findings on the meaning and
      experience of disability suggest the need for modifications to routinely used
      survey questions and for different ways of understanding the need for and receipt
      of care among older people with disabilities. The diverse risk factors for
      disability suggest that novel approaches across social, psychological as well as
      more traditional rehabilitation and behavioural risk factor modification would be
      worth exploring. Complex interventions appeared to help older people to live
      independently and limit functional decline irrespective of age and health status.

PMID- 18806192
TI  - MOBILE and the provision of total joint replacement.
AB  - Modern joint replacements have been available for 45 years, but we still do not
      have clear indications for these interventions, and we do not know how to
      optimize the outcome for patients who agree to have them done. The MOBILE
      programme has been investigating these issues in relation to primary total hip
      and knee joint replacements, using mixed methods research. There have been five
      main strands: (1) Epidemiological investigations to find out who is receiving
      total hip and knee replacements in the National Health Service (NHS). This has
      shown that there are extensive variations in different regions of the UK, with
      inequalities and probable inequities in the provision of these operations; (2)
      Epidemiological work to ascertain the population-based needs for the operations,
      showing under-provision of knee joint replacements, and a relative reluctance of
      both patients and GPs to consider knee surgery; (3) Quantitative and qualitative
      research into the views of patients, health care professionals and the public on
      the indications for, and prioritization of, total hip and knee joint
      replacements. This has shown lack of agreement within or between professional
      groups, as well as a mismatch between the views of patients and the public, and
      those of professionals; (4) Theoretical and experimental work on patient-related
      outcome measures, and the development of new instruments to assess both pain and
      function in people with osteoarthritis, based on the International Classification
      of Function, as well as a new integrated model of function; (5) Cohort studies of
      patients undergoing hip or knee joint replacements to find out what the
      determinants of good and bad outcomes are. These studies have emphasized the huge
      variation in disease severity at the time of surgery. The challenge now is to use
      and implement our findings for maximum patient benefit.

PMID- 18806193
TI  - Evidence-based diagnosis.
AB  - Making an accurate diagnosis is essential to ensure that a patient receives
      appropriate treatment and correct information regarding their prognosis.
      Characteristics of diagnostic tests are quantified in test accuracy studies, but
      many such studies have methodological flaws. The HSRC evidence-based diagnosis
      programme has focused on methods for systematic reviews of test accuracy studies,
      and the wider context in which tests are ordered and interpreted. We carried out
      a range of projects relating to literature searching, quality assessment, meta
      analysis, presentation of results, and interactions between doctors and patients
      during the diagnostic process. We have shown that systematic reviews of test
      accuracy studies should search a range of databases and that current diagnostic
      filters do not have sufficient accuracy to be used in test accuracy reviews.
      Summary quality scores should not be used in test accuracy reviews; the Quality
      Assessment of Studies of Diagnostic Accuracy included in Systematic Reviews
      (QUADAS) tool for assessing test accuracy studies is acceptable for quality
      assessment. We have shown that the hierarchical summary receiver operating
      characteristic (HSROC) and bivariate models for meta-analysis of test accuracy
      are statistically equivalent in many circumstances, and have developed an add-on
      module for the statistical software package Stata that enables these
      statistically rigorous models to be fitted by those without expert statistical
      knowledge. Three areas that would benefit from further research are literature
      searching, synthesis of results from individual patient data and presentation of
      results.

PMID- 18806194
TI  - Designing and implementing behaviour change interventions to improve population
      health.
AB  - Improved population health depends on changing behaviour: of those who are
      healthy (e.g. stopping smoking), those who are ill (e.g. adhering to health
      advice) and those delivering health care. To design more effective behaviour
      change interventions, we need more investment in developing the scientific
      methods for studying behaviour change. Behavioural science is relevant to all
      phases of the process of implementing evidence-based health care: developing
      evidence through primary studies, synthesizing the findings in systematic
      reviews, translating evidence into guidelines and practice recommendations, and
      implementing these in practice. 'Behaviour change: Implementation and Health',
      the last research programme to be funded within the MRC HSRC, aimed to develop
      innovative ways of applying theories and techniques of behaviour change to
      understand and improve the implementation of evidence-based practice, as a key
      step to improving health. It focused on four areas of study that apply behaviour
      change theory:defining and developing a taxonomy of behaviour change techniques
      to allow replication of studies and the possibility of accumulating evidence;
      conducting systematic reviews, by categorizing and synthesizing interventions on
      the basis of behaviour change theory; investigating the process by which evidence
      is translated into guideline recommendations for practice; developing a
      theoretical framework to apply to understanding implementation problems and
      designing interventions. This work will contribute to advancing the science of
      behaviour change by providing tools for conceptualizing and defining intervention
      content, and linking techniques of behaviour change to their theoretical base.

PMID- 18806195
TI  - Measuring and valuing mental health for use in economic evaluation.
AB  - This article presents research undertaken as part of a wider programme of work
      concerned with measuring and health and wellbeing for economic evaluation. The
      focus is on developing quality adjusted life years (QALYs) in mental health, but
      the issues are common across all areas of health care. The article begins by
      reviewing the issues of what should be valued (health or broader notions of
      wellbeing), how mental health and wellbeing should be described, how mental
      health states should be valued and who should do the valuing. The article
      presents four pieces of work. The first is a re-analysis of the ONS Psychiatric
      Morbidity 2000 Survey to provide evidence on the relevance of generic measures
      across different mental health disorders. It found that common mental health
      problems, such as anxiety and depression, had a significant impact on the generic
      preference-based measure of health in the SF-6D, but psychosis and personality
      disorders did not. The article then presents two studies using the ratings of
      people experiencing the states of health. Both studies found that people
      experiencing different health states gave mental health greater weight than
      physical health compared to members of the general public trying to imagine the
      health states. Finally, the article presents a study developing a condition
      specific preference-based measure for calculating QALYs from an existing measure
      of mental health, the CORE-OM, using modern psychometric methods to construct
      health states amenable to valuation. It also considers a proposal to develop an
      entirely new QALY measure in mental health.

PMID- 18806196
TI  - Consumer involvement in setting the health services research agenda: persistent
      questions of value.
AB  - Interest in consumer involvement in health services research started to gain
      momentum at around the same time that the MRC Health Services Research
      Collaboration (HSRC) was established. Consumer involvement was not the focus of a
      formal research programme within the HSRC, but HSRC members took opportunities to
      conduct three projects relating to consumer involvement in research agenda
      setting activities. These were: (1) a comparison of the focus of published
      research relating to the management of osteoarthritis of the knee with
      clinicians' and patients' ideas about research priorities; (2) a survey that
      examined the consumer involvement policies of public- and voluntary-sector
      organizations that fund health services research in the UK; and (3) a citizens'
      jury that was convened to develop priorities for research relating to primary
      health and social care in the Bristol area. This paper reviews the findings of
      these projects and highlights the continued need for attention to underlying
      values in the development and evaluation of future efforts to involve consumers
      in research agenda setting.

PMID- 18806197
TI  - Reducing the burden of chronic wounds: prevention and management of the diabetic
      foot in the context of clinical guidelines.
AB  - OBJECTIVES: Chronic wounds such as diabetic foot and venous leg ulcers are a
      major burden for health services. Our programme was developed to explore the
      psychological and behavioural factors that may influence both the incidence of
      chronic wounds and their progression. The present article focuses on two
      particular aspects of the programme: patient knowledge of diabetic foot
      ulceration and factors influencing foot-related behaviour in patients with and
      without foot ulcers; and patient and podiatrist perspectives of consultations for
      diabetic foot ulcers. METHODS: Two independent qualitative studies were
      undertaken: one with diabetic patients without a history of ulceration; and the
      other with diabetic patients with active ulceration and podiatrists treating
      these patients. RESULTS: We found that patients may find it difficult
      understanding the rationale underlying prevention and treatment of foot ulcers;
      ulcerated patients may find it difficult to engage in the management of their
      foot ulcer outside consultations; and some podiatrists feel frustrated and
      unsupported in their attempts at empowering and building partnerships with
      patients. CONCLUSION: Patient and practitioner factors may contribute to the
      effective implementation of clinical guidelines regarding education, partnership
      building and shared decision-making. These findings are discussed in relation to
      patient education, partnership building and shared decision-making as recommended
      in NICE guidelines.

PMID- 18806198
TI  - Using qualitative research methods to improve recruitment to randomized
      controlled trials: the Quartet study.
AB  - OBJECTIVE: Randomized controlled trials (RCTs) are considered the optimum method
      for evaluating health care interventions, yet many fail to recruit sufficient
      participants in a timely manner. The ProtecT (Prostate testing for cancer and
      Treatment) study employed qualitative research methods as part of a complex
      intervention to improve recruitment to the RCT. The Quartet (Qualitative research
      to improve recruitment to trials) study was set up to evalute whether the ProtecT
      study's success in increasing randomization rates could be replicated in other
      trials experiencing recruitment difficulties. This paper reports on the issues
      that emerged from the attempts to apply qualitative research methods to improve
      recruitment rates in RCTs collaborating with the Quartet team. METHODS: The
      methods used were: investigation of RCT documents; semi-structured interviews and
      focus groups with RCT staff; audio-recording of recruitment appointments; and
      individual and group feedback sessions for RCT staff. Data were analysed using
      content and thematic analysis. RESULTS: Barriers arose when we attempted to
      establish collaborations with RCTs. Difficulties were encountered in securing the
      commitment of all relevant staff because of poor communication between lead
      investigators and other staff as well as RCT staff's concerns about having
      recruitment appointments audio-recorded. Recruitment processes were often more
      complex than anticipated. Governance procedures took considerable time and
      resources, limiting the time available for data collection and implementation of
      the intervention before recruitment closure. CONCLUSION: Straightforward
      replication of the ProtecT complex intervention was more complicated than
      expected. However, the study has increased understanding of RCT recruitment and
      identified ways to overcome barriers to collaboration. Such research is more
      easily undertaken in the feasibility stage of an RCT, and greater success will be
      achieved if the research is integrated into the everyday conduct of RCTs.

PMID- 18806199
TI  - Trust relations in a changing health service.
AB  - OBJECTIVE: Trust in health care is an important policy area although research has
      tended to focus on interpersonal trust between patient and practitioner and has
      neglected trust relations at the organizational and institutional levels. Each of
      these levels of trust may have been influenced by recent policy and
      organizational changes in the NHS as well as wider cultural changes. Our aim was
      to explore the relationship between patients, practitioners and managers to
      identify if there was any evidence of changes in trust relations. METHOD: A
      comparative case study design in two different clinical and organizational
      settings. RESULTS: Trust is still important for effective therapeutic and working
      relationships but the nature of that trust and how it is lost and won appears to
      be affected by the organizational context in which health services are delivered.
      The increasing partnership between patients and clinicians in managing health
      problems and the greater inter-dependence of clinicians and managers in providing
      multidisciplinary shared care have changed how patients, clinicians and managers
      trust each other. For many informants trust can no longer be assumed, it is
      conditional and has to be earned. However, the sources of trust are the quality
      of the patient-clinician interaction, the competence and empathy that is
      displayed rather than informed trust based on abstract disembodied data. Likewise
      in inter-practitioner relationships and clinician-manager relations trust no
      longer appears to be primarily based on professional status and seniority,
      instead it appears to be conditional and may be earned through a variety of
      strategies that demonstrate honesty, reliability, competence, accessibility and
      an indication that colleagues share similar values and have a common agenda.
      CONCLUSION: Trust is still important for effective therapeutic and working
      relationships.

PMID- 18806200
TI  - Patient preferences for treatment for angina: an overview of findings from three
      studies.
AB  - BACKGROUND: Access to cardiac treatments has been documented to vary with
      patients' age. It is unknown whether these variations reflect patients' treatment
      preferences. We aimed to investigate patients' preferences for cardiology
      treatments and develop a Patients' Preferences Questionnaire. METHODS: Semi
      structured interviews with primary care patients with diagnosed angina with
      postal follow-up. The resulting Patients' Preferences Questionnaire was tested
      with newly admitted inpatients with acute coronary syndrome and with patients in
      primary care. RESULTS: The Patients' Preferences Questionnaire was
      psychometrically sound. Analyses of preference subscale scores showed that the
      most positive preference scores were for medication. Angioplasty scored highest
      at the negative end of the scale. Detailed analyses showed that older people and
      women were less likely to prefer coronary artery bypass surgery (CABG),
      reflecting its greater level of invasiveness. Older people (aged over 75 years,
      compared to people aged under 75 years), but not women, were also more cautious
      in their strength of preference for angioplasty. More positive attitudes towards
      CABG surgery, and more negative attitudes towards medication, were associated
      with greater impact of the condition on life. CONCLUSIONS: The research resulted
      in a psychometrically sound Patients' Preferences Questionnaire. There was some
      evidence to support the view that older people's weaker preferences for CABG may
      contribute slightly to variations in the provision of re-vascularization. There
      was also variation in preferences within age groups, cautioning against the
      assumption that all or most older people are more reluctant than younger people
      to undergo invasive procedures.

PMID- 18806201
TI  - Compression therapy in venous disease.

PMID- 18806202
TI  - Endovenous laser ablation: mechanism of action.
AB  - OBJECTIVES: The objective of this study is to review the basics of laser and
      established tissue response patterns to thermal injury, with specific reference
      to endovenous laser ablation (EVLA). This study also reviews the current theories
      and supporting aspects for the mechanism of action of EVLA in the treatment of
      superficial venous reflux. METHODS: The method involves the review of published
      literature and original investigation of histological effects of 810 nm and 980
      nm wavelength EVLA on explanted blood-filled bovine saphenous vein in an in vitro
      system. RESULTS: The existing histological reports confirm that EVLA produces a
      transmural vein wall injury, typically associated with perforations and
      carbonization. The pattern of injury is eccentrically distributed, with maximum
      injury occurring along the path of laser contact. Intravenous temperature
      monitoring studies during EVLA have confirmed that the peak temperatures at the
      fibre tip exceed 1000 degrees C, and continuous temperatures of at least 300
      degrees C are maintained in the firing zone for the majority of the procedure.
      Steam production during EVLA, which occurs early in the photothermolytic process
      when temperatures reach 100 degrees C, accounts for only 2% of applied energy
      dose, and is therefore unlikely to be the primary mechanism of action of thermal
      injury during the procedure. CONCLUSION: EVLA causes permanent vein closure
      through a high-temperature photothermolytic process at the point of contact
      between the vein and the laser.

PMID- 18806203
TI  - Leg symptoms of healthy people and their treatment with compression hosiery.
AB  - OBJECTIVES: Occasional leg symptoms, like feelings of heaviness and tension, and
      occupational or evening oedema are considered typical features of a venous
      disorder but show low specificity in epidemiological and observational studies.
      We evaluated the prevalence and nature of such symptoms in subjects with no
      history or signs of venous disease and investigated the optimal strength that
      medical compression stockings (MCS) should exert in order to alleviate the
      symptoms and to prevent leg swelling. METHODS: Specifically designed
      questionnaires were used to assess the symptoms of 40 healthy employees of a
      factory producing MCS. Lower leg volumes were quantified in the morning and
      evening. Calf size hosiery providing documented ankle pressures of 4-9 (mean
      7.3), 12-18 (mean 14.9) and 18-22 (mean 19.5) mmHg, respectively, were tested in
      a prospective, open-label, randomized trial lasting three weeks. Endpoints were
      the relief of symptoms, prevention of vesperal oedema and comfort in wearing the
      stockings. RESULTS: Sixty-five percent of the participants reported at least
      occasional leg symptoms and oedema. Somatic-type symptoms (i.e. pain, heaviness,
      swelling, unattractive legs) were present in two, psychic-type symptoms (i.e. leg
      and personality-related unrest and stress) in 17 and both components in seven of
      the 40 subjects. MCS exerting 15 and 20 mmHg prevented the symptoms and oedema.
      Stockings providing <10 mmHg were ineffective and those providing >19 mmHg were
      not well-tolerated. The effect on the somatic-type symptoms was strongly
      correlated with the amount of lower leg volume which could be reduced by wearing
      stockings (P = 0.005). No correlation was found between the efficacy of
      compression and the emotional component of the symptoms. CONCLUSION: The cause of
      occasional pain in the legs of apparently healthy people is unknown. Some
      features of the syndrome reflect an emotional disorder while others mirror venous
      insufficiency. MCS of 15 mmHg effectively relieve the symptoms resembling venous
      insufficiency, prevent oedema and are well-tolerated.

PMID- 18806204
TI  - The effect of nitroglycerin ointment on great saphenous vein targeted venous
      access site diameter with endovenous laser treatment.
AB  - OBJECTIVES: To assess the effect of topically applied nitroglycerin (NTG)
      ointment (2%) on preoperative targeted venous access site great saphenous vein
      (GSV) diameter in patients undergoing endovenous laser treatment (ELT). METHODS:
      In this double-blinded randomized study design, 75 patients received either (A)
      treadmill ambulation only, (B) topically applied NTG ointment only, or (C)
      topically applied NTG ointment + treadmill ambulation. Targeted venous access
      vein diameters were measured before therapeutic intervention and then repeated
      after approximately 30 min following pretreatment intervention. Presence of
      venospasm and the number of ultrasound-guided venous access attempts during each
      ELT procedure were assessed during the study. RESULTS: The mean pretreatment vein
      diameter was 2.6 mm (range 0.9-4.9 mm). The post-treatment percentage change in
      vein diameter for group A (treadmill ambulation only) was +2.7% (P = 0.403),
      whereas group B (NTG only) and group C (NTG + treadmill ambulation) demonstrated
      significant venodilatation of +69.0% (P < 0.0001) and +51.7% (P < 0.0001),
      respectively. Statistical analysis of variances and multivariate linear
      regression model revealed topically applied NTG ointment and 'C' classification
      of clinical, aetiological, anatomical and pathological elements (CEAP) were each
      significant predictors for venodilatation percentage change (P < 0.001 and =
      0.028, respectively). CONCLUSION: Pretreatment with topically applied NTG
      ointment (2%) produced a statistically significant, as well as subjective
      clinically significant venodilatation change in the targeted venous access site
      diameter of patients undergoing ELT of the GSV in this study.

PMID- 18806205
TI  - The use of autologous femoral vein for the repair of the common iliac vein after
      resection of a pheochromocytoma.
AB  - AIM: To illustrate the use of autologous femoral vein for grafting ilio-caval
      vein defects following abdomino-pelvic tumour resections. METHODS: Case report
      and literature review. RESULTS: Durable restoration of ilio-caval patency was
      achieved, with minimal morbidity from graft harvesting. CONCLUSIONS: Autologous
      femoral vein presents a viable graft option for the immediate reconstruction of
      large intra-abdominal vein deficits.

PMID- 18806206
TI  - Letter regarding article titled 'microembolism during foam sclerotherapy of
      varicose veins' in the New England Journal of Medicine.

PMID- 18806208
TI  - Transgenic rodent Plasmodium berghei parasites as tools for assessment of
      functional immunogenicity and optimization of human malaria vaccines.

PMID- 18806209
TI  - The cell wall of the human pathogen Candida glabrata: differential incorporation
      of novel adhesin-like wall proteins.
AB  - The cell wall of the human pathogen Candida glabrata governs initial host
      pathogen interactions that underlie the establishment of fungal infections. With
      the aim of identifying species-specific features that may directly relate to its
      virulence, we have investigated the cell wall of C. glabrata using a
      multidisciplinary approach that combines microscopy imaging, biochemical studies,
      bioinformatics, and tandem mass spectrometry. Electron microscopy revealed a
      bilayered wall structure in which the outer layer is packed with mannoproteins.
      Biochemical studies showed that C. glabrata walls incorporate 50% more protein
      than Saccharomyces cerevisiae walls and, consistent with this, have a higher
      mannose/glucose ratio. Evidence is presented that C. glabrata walls contain
      glycosylphosphatidylinositol (GPI) proteins, covalently bound to the wall 1,6
      beta-glucan, as well as proteins linked through a mild-alkali-sensitive linkage
      to 1,3-beta-glucan. A comprehensive genome-wide in silico inspection showed that
      in comparison to other fungi, C. glabrata contains an exceptionally large number,
      67, of genes encoding adhesin-like GPI proteins. Phylogenetically these adhesin
      like proteins form different clusters, one of which is the lectin-like EPA
      family. Mass spectrometric analysis identified 23 cell wall proteins, including 4
      novel adhesin-like proteins, Awp1/2/3/4, and Epa6, which is involved in adherence
      to human epithelia and biofilm formation. Importantly, the presence of adhesin
      like proteins in the wall depended on the growth stage and on the genetic
      background used, and this was reflected in alterations in adhesion capacity and
      cell surface hydrophobicity. We propose that the large repertoire of adhesin(
      like) genes of C. glabrata contributes to its adaptability and virulence.

PMID- 18806210
TI  - Nonapoptotic death of Saccharomyces cerevisiae cells that is stimulated by Hsp90
      and inhibited by calcineurin and Cmk2 in response to endoplasmic reticulum
      stresses.
AB  - Endoplasmic reticulum (ER) stress can trigger apoptosis and necrosis in many
      types of mammalian cells. Previous studies in yeast found little or no cell death
      in response to the ER stressor tunicamycin, but a recent study suggested
      widespread apoptosis-like death. Here we show that wild-type laboratory
      Saccharomyces cerevisiae cells responding to tunicamycin die by nonapoptotic
      mechanisms in low-osmolyte culture media and survive for long periods of time in
      standard synthetic media. Survival requires calcineurin, a Ca(2+)/calmodulin
      dependent protein phosphatase, but none of its known targets. The
      Ca(2+)/calmodulin-dependent protein kinase Cmk2 was identified as an indirect
      target of calcineurin that suppresses death of calcineurin-deficient cells. Death
      of Cmk2- and/or calcineurin-deficient S. cerevisiae cells was preceded by
      accumulation of reactive oxygen species but was not associated with hallmarks of
      apoptosis and was not dependent on Mca1, Aif1, Nuc1, or other factors implicated
      in apoptosis-like death. Cmk2 and calcineurin also independently suppressed the
      death of S. cerevisiae cells responding to dithiothreitol or miconazole, a common
      azole-class antifungal drug. Though inhibitors of Hsp90 have been shown to
      diminish calcineurin signaling in S. cerevisiae and to synergistically inhibit
      growth in combination with azoles, they did not stimulate death of S. cerevisiae
      cells in combination with miconazole or tunicamycin, and instead they prevented
      the death of calcineurin- and Cmk2-deficient cells. These findings reveal a novel
      prodeath role for Hsp90 and antideath roles for calcineurin and Cmk2 that extend
      the life span of S. cerevisiae cells responding to both natural and clinical
      antifungal compounds.

PMID- 18806211
TI  - Oxygen-dependent transcriptional regulator Hap1p limits glucose uptake by
      repressing the expression of the major glucose transporter gene RAG1 in
      Kluyveromyces lactis.
AB  - The HAP1 (CYP1) gene product of Saccharomyces cerevisiae is known to regulate the
      transcription of many genes in response to oxygen availability. This response
      varies according to yeast species, probably reflecting the specific nature of
      their oxidative metabolism. It is suspected that a difference in the interaction
      of Hap1p with its target genes may explain some of the species-related variation
      in oxygen responses. As opposed to the fermentative S. cerevisiae, Kluyveromyces
      lactis is an aerobic yeast species which shows different oxygen responses. We
      examined the role of the HAP1-equivalent gene (KlHAP1) in K. lactis. KlHap1p
      showed a number of sequence features and some gene targets (such as KlCYC1) in
      common with its S. cerevisiae counterpart, and KlHAP1 was capable of
      complementing the hap1 mutation. However, the KlHAP1 disruptant showed
      temperature-sensitive growth on glucose, especially at low glucose
      concentrations. At normal temperature, 28 degrees C, the mutant grew well, the
      colony size being even greater than that of the wild type. The most striking
      observation was that KlHap1p repressed the expression of the major glucose
      transporter gene RAG1 and reduced the glucose uptake rate. This suggested an
      involvement of KlHap1p in the regulation of glycolytic flux through the glucose
      transport system. The DeltaKlhap1 mutant showed an increased ability to produce
      ethanol during aerobic growth, indicating a possible transformation of its
      physiological property to Crabtree positivity or partial Crabtree positivity.
      Dual roles of KlHap1p in activating respiration and repressing fermentation may
      be seen as a basis of the Crabtree-negative physiology of K. lactis.

PMID- 18806212
TI  - ESCRT-III protein Snf7 mediates high-level expression of the SUC2 gene via the
      Rim101 pathway.
AB  - The yeast (Saccharomyces cerevisiae) Snf7 family consists of six highly charged,
      coiled-coil-forming proteins involved in multivesicular body (MVB) formation.
      Although all proteins perform a common function at late endosomes, individual
      mutants also show distinct phenotypes. This suggests that Snf7 homologues have
      additional functions separate from their role in MVB formation. In this report,
      we explored the molecular basis for the sucrose-nonfermenting phenotype of snf7
      mutants. Our Northern blotting experiments provide evidence that Snf7 is involved
      in the regulation of SUC2 transcription. The Snf7-dependent regulation of SUC2
      transcription does not appear to involve the transcription factor Mig1, since
      Mig1 phosphorylation after glucose derepression was not affected in a Deltasnf7
      mutant. Instead, we show that Snf7 influences SUC2 expression by regulating the
      level of the transcription factor Nrg1. Snf7 exerts its effects on Nrg1 levels
      through activation of the transcription factor Rim101, which is part of the yeast
      alkaline response pathway ("Rim101 pathway"). This is supported by the findings
      that deletion of RIM101 or overexpression of NRG1 from the ADH1 promoter leads to
      the same SUC2 expression level as deletion of SNF7. In addition, deletion of
      other components of the Rim101 pathway, like RIM13 and RIM20, led to the same
      growth phenotype on raffinose media as deletion of SNF7. Furthermore, Snf7 turned
      out to be dispensable for SUC2 expression in an NRG1 deletion background. Thus,
      the effects of Snf7 on SUC2 expression can be completely accounted for by its
      effect on Nrg1 levels.

PMID- 18806213
TI  - The synthetic genetic network around PKC1 identifies novel modulators and
      components of protein kinase C signaling in Saccharomyces cerevisiae.
AB  - Budding yeast Saccharomyces cerevisiae contains one protein kinase C (PKC)
      isozyme encoded by the essential gene PKC1. Pkc1 is activated by the small GTPase
      Rho1 and plays a central role in the cell wall integrity (CWI) signaling pathway.
      This pathway acts primarily to remodel the cell surface throughout the normal
      life cycle and upon various environmental stresses. The pathway is heavily
      branched, with multiple nonessential branches feeding into and out of the central
      essential Rho1-Pkc1 module. In an attempt to identify novel components and
      modifiers of CWI signaling, we determined the synthetic lethal genetic network
      around PKC1 by using dominant-negative synthetic genetic array analysis. The
      resulting mutants are hypersensitive to lowered Pkc1 activity. The corresponding
      21 nonessential genes are closely related to CWI function: 14 behave in a
      chemical-genetic epistasis test as acting in the pathway, and 6 of these genes
      encode known components. Twelve of the 21 null mutants display elevated CWI
      reporter activity, consistent with the idea that the pathway is activated by and
      compensates for loss of the gene products. Four of the 21 mutants display low CWI
      reporter activity, consistent with the idea that the pathway is compromised in
      these mutants. One of the latter group of mutants lacks Ack1(Ydl203c), an
      uncharacterized SEL-1 domain-containing protein that we find modulates pathway
      activity. Epistasis analysis places Ack1 upstream of Pkc1 in the CWI pathway and
      dependent on the upstream Rho1 GTP exchange factors Rom2 and Tus1. Overall, the
      synthetic genetic network around PKC1 directly and efficiently identifies known
      and novel components of PKC signaling in yeast.

PMID- 18806214
TI  - Cell wall chitosaccharides are essential components and exposed patterns of the
      phytopathogenic oomycete Aphanomyces euteiches.
AB  - Chitin is an essential component of fungal cell walls, where it forms a
      crystalline scaffold, and chitooligosaccharides derived from it are signaling
      molecules recognized by the hosts of pathogenic fungi. Oomycetes are cellulosic
      fungus-like microorganisms which most often lack chitin in their cell walls. Here
      we present the first study of the cell wall of the oomycete Aphanomyces
      euteiches, a major parasite of legume plants. Biochemical analyses demonstrated
      the presence of ca. 10% N-acetyl-D-glucosamine (GlcNAc) in the cell wall. Further
      characterization of the GlcNAc-containing material revealed that it corresponds
      to noncrystalline chitosaccharides associated with glucans, rather than to chitin
      per se. Two putative chitin synthase (CHS) genes were identified by data mining
      of an A. euteiches expressed sequence tag collection and Southern blot analysis,
      and full-length cDNA sequences of both genes were obtained. Phylogeny analysis
      indicated that oomycete CHS diversification occurred before the divergence of the
      major oomycete lineages. Remarkably, lectin labeling showed that the Aphanomyces
      euteiches chitosaccharides are exposed at the cell wall surface, and study of the
      effect of the CHS inhibitor nikkomycin Z demonstrated that they are involved in
      cell wall function. These data open new perspectives for the development of
      antioomycete drugs and further studies of the molecular mechanisms involved in
      the recognition of pathogenic oomycetes by the host plants.

PMID- 18806215
TI  - Establishing a new animal model for the study of laryngeal biology and disease:
      an anatomic study of the mouse larynx.
AB  - PURPOSE: Animal models have contributed greatly to the study of voice, permitting
      the examination of laryngeal biology and the testing of surgical, medical, and
      behavioral interventions. Various models have been used. However, until recently,
      the mouse (Mus musculus) has not been used in laryngeal research, and features of
      the mouse larynx have not been defined. Therefore, the purpose of this study was
      to qualitatively describe mouse laryngeal anatomy in relation to known human
      anatomy. METHODS: Larynges of 7 C57BL mice were examined and photographed under
      stereotactic and light microscopy. RESULTS: The authors found that mouse
      laryngeal organization was similar to that of humans. The hyoid bone and
      epiglottal, thyroid, cricoid, and arytenoid cartilages were identified. An
      additional cartilage was present ventrally. Thyroarytenoid, posterior
      cricoarytenoid, lateral cricoarytenoid, and cricothyroid muscles were grossly
      positioned as in humans. Interarytenoid muscles were not present; however, a
      functional counterpart was identified. CONCLUSIONS: The authors provide an
      initial description of mouse laryngeal anatomy. Because of its amenability to
      genetic engineering, the mouse is the premiere model for the study of disease and
      the testing of interventions. Introduction of the mouse model for laryngeal study
      offers a tool for the study of normal laryngeal cell biology and tissue response
      to disease processes.

PMID- 18806216
TI  - The effect of temporal gap identification on speech perception by users of
      cochlear implants.
AB  - PURPOSE: This study examined the ability of listeners using cochlear implants
      (CIs) and listeners with normal hearing (NH) to identify silent gaps of different
      duration and the relation of this ability to speech understanding in CI users.
      METHOD: Sixteen NH adults and 11 postlingually deafened adults with CIs
      identified synthetic vowel-like stimuli that were either continuous or contained
      an intervening silent gap ranging from 15 ms to 90 ms. Cumulative d', an index of
      discriminability, was calculated for each participant. Consonant and consonant
      nucleus-consonant (CNC) word identification tasks were administered to the CI
      group. RESULTS: Overall, the ability to identify stimuli with gaps of different
      duration was better for the NH group than for the CI group. Seven CI users had
      cumulative d' scores that were no higher than those of any NH listener, and their
      CNC word scores ranged from 0% to 30%. The other 4 CI users had cumulative d'
      scores within the range of the NH group, and their CNC word scores ranged from
      46% to 68%. For the CI group, cumulative d' scores were significantly correlated
      with their speech testing scores. CONCLUSIONS: The ability to identify silent gap
      duration may help explain individual differences in speech perception by CI
      users.

PMID- 18806217
TI  - The cystic fibrosis transmembrane conductance regulator and chloride-dependent
      ion fluxes of ovine vocal fold epithelium.
AB  - PURPOSE: Ion-driven transepithelial water fluxes participate in maintaining
      superficial vocal fold hydration, which is necessary for normal voice production.
      The authors hypothesized that Cl(-) channels are present in vocal fold epithelial
      cells and that transepithelial Cl(-) fluxes can be manipulated pharmacologically.
      METHOD: Immunohistochemical assays were used to identify cystic fibrosis
      transmembrane regulator Cl(-) channels in ovine vocal fold mucosae (n = 2).
      Electrophysiological responses of vocal fold mucosae (n = 80) to Cl(-) channel
      inhibitors and secretagogues were evaluated in an ovine model using a randomized
      controlled experimental design. RESULTS: Cystic fibrosis transmembrane regulator
      channels were localized to the plasma membranes of epithelial cells. The Cl(-)
      transport inhibitor, diphenylamine-2-carboxylate, elicited a 30% decrease in mean
      short-circuit current (I(sc); n = 10). The secretagogue, isobutylmethylxanthine,
      yielded a 31.7% increase in mean I(sc) (n = 10). Another secretagogue, uridine
      triphosphate, elicited a 48.8% immediate and 17.3% sustained increase in mean
      I(sc) (n = 10). No sustained increases occurred following application of
      secretagogues to mucosae bathed in a low Cl(-) environment (n = 10), suggesting
      that responses were Cl(-) dependent. CONCLUSIONS: The authors provide structural
      and functional evidence for the presence of a transepithelial pathway for Cl(-)
      fluxes. Pharmacological manipulation of this pathway may offer a mechanism for
      maintaining superficial vocal fold hydration.

PMID- 18806218
TI  - Insulin secretion is highly sensitive to desorption of plasma membrane
      cholesterol.
AB  - Cholesterol-rich clusters of SNARE (soluble NSF attachment protein receptor)
      proteins have been implicated as being important for exocytosis. Here we
      demonstrate the significance of cholesterol for normal biphasic insulin secretion
      in mouse beta cells by removal of cholesterol from the plasma membrane using
      methyl-beta-cyclodextrin (MBCD). Maximal inhibition of insulin secretion in
      static incubations was achieved using 0.1 mM MBCD. In in situ pancreatic
      perfusion measurements, both first and second phase insulin secretions were
      reduced by approximately 50% (P<0.05). This was accompanied by a reduced number
      of docked large dense core vesicles (LDCVs) (approximately 40%; P<0.01) and a
      reduced exocytotic response (>50%; P<0.01). Further, subcellular fractionations
      demonstrated movement of the synaptosomal protein of 25 kDa (SNAP-25) from the
      plasma membrane to the cytosol after MBCD treatment. The inhibitory actions of
      MBCD were counteracted by subsequent addition of cholesterol. We hypothesize that
      desorption of cholesterol leads to the disturbance of a basic exocytotic
      mechanism partly due to migration of SNAP-25, and we conclude that insulin
      secretion is highly sensitive to changes in plasma membrane cholesterol.

PMID- 18806221
TI  - The inner of the two Muc2 mucin-dependent mucus layers in colon is devoid of
      bacteria.
AB  - We normally live in symbiosis with approximately 10(13) bacteria present in the
      colon. Among the several mechanisms maintaining the bacteria/host balance, there
      is limited understanding of the structure, function, and properties of intestinal
      mucus. We now demonstrate that the mouse colonic mucus consists of two layers
      extending 150 mum above the epithelial cells. Proteomics revealed that both of
      these layers have similar protein composition, with the large gel-forming mucin
      Muc2 as the major structural component. The inner layer is densely packed, firmly
      attached to the epithelium, and devoid of bacteria. In contrast, the outer layer
      is movable, has an expanded volume due to proteolytic cleavages of the Muc2
      mucin, and is colonized by bacteria. Muc2(-/-) mice have bacteria in direct
      contact with the epithelial cells and far down in the crypts, explaining the
      inflammation and cancer development observed in these animals. These findings
      show that the Muc2 mucin can build a mucus barrier that separates bacteria from
      the colon epithelia and suggest that defects in this mucus can cause colon
      inflammation.

PMID- 18806222
TI  - The convergence of carbohydrate active gene repertoires in human gut microbes.
AB  - The extreme variation in gene content among phylogenetically related
      microorganisms suggests that gene acquisition, expansion, and loss are important
      evolutionary forces for adaptation to new environments. Accordingly,
      phylogenetically disparate organisms that share a habitat may converge in gene
      content as they adapt to confront shared challenges. This response should be
      especially pronounced for functional genes that are important for survival in a
      particular habitat. We illustrate this principle by showing that the repertoires
      of two different types of carbohydrate-active enzymes, glycoside hydrolases and
      glycosyltransferases, have converged in bacteria and archaea that live in the
      human gut and that this convergence is largely due to horizontal gene transfer
      rather than gene family expansion. We also identify gut microbes that may have
      more similar dietary niches in the human gut than would be expected based on
      phylogeny. The techniques used to obtain these results should be broadly
      applicable to understanding the functional genes and evolutionary processes
      important for adaptation in many environments and useful for interpreting the
      large number of reference microbial genome sequences being generated for the
      International Human Microbiome Project.

PMID- 18806223
TI  - Backtracking on the folding landscape of the beta-trefoil protein interleukin
      1beta?
AB  - Interleukin-1beta (IL-1beta) is a cytokine within the beta-trefoil family. Our
      data indicate that the folding/unfolding routes are geometrically frustrated.
      Follow-up theoretical studies predicted backtracking events that could contribute
      to the broad transition barrier and the experimentally observed long-lived
      intermediate. The backtracking route is attributed to the topological frustration
      introduced by the packing of the functional loop (the beta-bulge, residues 47-53)
      to the nascent barrel. We used real-time refolding NMR experiments to test for
      the presence of backtracking events predicted from our theoretical studies.
      Structural variants of IL-1beta, a beta-bulge deletion, and a circular
      permutation that opens the protein in the middle of the experimentally observed
      kinetic intermediate, were also refolded and studied to determine the affects on
      the observed folding reactions. The functional loop deletion variant demonstrated
      less backtracking than in WT protein whereas the permutation still maintains
      backtracking in agreement with theoretical predictions. Taken together, these
      findings indicate that the backtracking results from geometric frustration
      introduced into the fold for functional purposes.

PMID- 18806224
TI  - Effective rescue of dystrophin improves cardiac function in dystrophin-deficient
      mice by a modified morpholino oligomer.
AB  - Antisense oligonucleotide-mediated exon skipping is able to correct out-of-frame
      mutations in Duchenne muscular dystrophy and restore truncated yet functional
      dystrophins. However, its application is limited by low potency and inefficiency
      in systemic delivery, especially failure to restore dystrophin in heart. Here, we
      conjugate a phosphorodiamidate morpholino oligomer with a designed cell
      penetrating peptide (PPMO) targeting a mutated dystrophin exon. Systemic delivery
      of the novel PPMO restores dystrophin to almost normal levels in the cardiac and
      skeletal muscles in dystrophic mdx mouse. This leads to increase in muscle
      strength and prevents cardiac pump failure induced by dobutamine stress in vivo.
      Muscle pathology and function continue to improve during the 12-week course of
      biweekly treatment, with significant reduction in levels of serum creatine
      kinase. The high degree of potency of the oligomer in targeting all muscles and
      the lack of detectable toxicity and immune response support the feasibility of
      testing the novel oligomer in treating Duchenne muscular dystrophy patients.

PMID- 18806225
TI  - Inflammation and autoimmunity caused by a SHP1 mutation depend on IL-1, MyD88,
      and a microbial trigger.
AB  - A recessive phenotype called spin (spontaneous inflammation) was induced by N
      ethyl-N-nitrosourea (ENU) mutagenesis in C57BL/6J mice. Homozygotes display
      chronic inflammatory lesions affecting the feet, salivary glands and lungs, and
      antichromatin antibodies. They are immunocompetent and show enhanced resistance
      to infection by Listeria monocytogenes. TLR-induced TNF and IL-1 production are
      normal in macrophages derived from spin mice. The autoinflammatory phenotype of
      spin mice is fully suppressed by compound homozygosity for Myd88(poc),
      Irak4(otiose), and Il1r1-null mutations, but not Ticam1(Lps2), Stat1(m1Btlr), or
      Tnf-null mutations. Both autoimmune and autoinflammatory phenotypes are
      suppressed when spin homozygotes are derived into a germ-free environment. The
      spin phenotype was ascribed to a viable hypomorphic allele of Ptpn6, which
      encodes the tyrosine phosphatase SHP1, mutated in mice with the classical
      motheaten alleles me and me-v. Inflammation and autoimmunity caused by SHP1
      deficiency are thus conditional. The SHP1-deficient phenotype is driven by
      microbes, which activate TLR signaling pathways to elicit IL-1 production. IL-1
      signaling via MyD88 elicits inflammatory disease.

PMID- 18806226
TI  - Sustained induction of epithelial to mesenchymal transition activates DNA
      methylation of genes silenced in basal-like breast cancers.
AB  - The active acquisition of epigenetic changes is a poorly understood but important
      process in development, differentiation, and disease. Our work has shown that
      repression of the p16/pRb pathway in human epithelial cells, a condition common
      to stem cells and many tumor cells, induces dynamic epigenetic remodeling
      resulting in the targeted methylation of a selected group of CpG islands. We
      hypothesized that cells in this epigenetically plastic state could be programmed
      by the microenvironment to acquire epigenetic changes associated with
      tumorigenesis. Here, we describe an in vitro model system where epigenetically
      plastic cells were placed in an environment that induced epithelial to
      mesenchymal transition (EMT) and led to a program of acquired de novo DNA
      methylation at targeted sites. In this model, we found that repression of E
      cadherin transcription preceded the subsequent acquisition of methylated CpG
      sites. Furthermore, the induction of EMT was accompanied by de novo methylation
      of several other gene promoters, including those of the estrogen receptor and
      Twist. These data demonstrate that signals from the microenvironment can induce
      phenotypic and gene expression changes associated with targeted de novo
      epigenetic alterations important in tumor progression, and that these alterations
      occur through a deterministic, rather than stochastic, mechanism. Given the
      dynamic epigenetic reprogramming that occurs in these cells, DNA methylation
      profiles observed in human tumors may reflect the history of environmental
      exposures during the genesis of a tumor.

PMID- 18806227
TI  - Pancreatic exocrine insufficiency in LXRbeta-/- mice is associated with a
      reduction in aquaporin-1 expression.
AB  - Liver X receptors (LXRs) alpha and beta are nuclear oxysterol receptors with a
      key role in cholesterol, triglyceride, and glucose metabolism. In LXRbeta(-/-)
      mice on a normal diet, there is a reduction in size of perigonadal fat pad and,
      on high-fat diet there is resistance to obesity. In the present study, we
      investigated the reason for the resistance of LXRbeta(-/-) mice to weight gain.
      In LXRbeta(-/-) mice we found pancreatic exocrine insufficiency with reduced
      serum levels of amylase and lipase, reduced proteolytic activity in feces,
      chronic inflammatory infiltration, and, in the ductal epithelium, an increased
      apoptosis without compensatory proliferation. Electron microscopy revealed ductal
      dilatation with intraductal laminar structures characteristic of cystic fibrosis.
      To investigate the relationship between LXRbeta and pancreatic secretion, we
      studied the expression of LXRbeta and the water channel, aquaporin-1 (AQP1), in
      the ductal epithelium of the pancreas. In WT mice, ductal epithelial cells
      expressed LXRbeta in the nuclei and AQP1 on the plasma membrane. In LXRbeta(-/-)
      mice neither LXRbeta nor AQP1 was detectable. Moreover, in WT mice the LXR
      agonist (T2320) increased AQP1 gene expression. These data demonstrate that in
      LXRbeta(-/-) mice dietary resistance to weight gain is caused by pancreatic
      insufficiency and that LXRbeta regulates pancreatic exocrine secretion through
      the control of AQP1 expression. Pancreatic exocrine insufficiency is the main
      cause of malabsorption syndrome responsible for weight loss in adults and growth
      failure in children. Several genes are known to be involved in the pathogenesis
      and susceptibility to pancreatic insufficiency. LXRbeta should be included in
      that list.

PMID- 18806229
TI  - Imaging of eating disorders: multiple techniques to demonstrate the dynamic
      brain.

PMID- 18806228
TI  - Association of genetic variants of methionine metabolism with methotrexate
      induced CNS white matter changes in patients with primary CNS lymphoma.
AB  - Methotrexate (MTX) is an important anticancer drug and the most efficient
      chemotherapy component in primary CNS lymphoma (PCNSL). A typical side effect of
      intravenous high-dose MTX is the occurrence of confluent CNS white matter changes
      (WMC). Because MTX directly interferes with methionine metabolism, we analyzed
      the impact of genetic variants of methionine metabolism on the occurrence of WMC
      as a model of MTX toxicity. In a retrospective analysis of 68 PCNSL patients
      treated with MTX-based polychemotherapy with (n = 42) or without (n = 26)
      intraventricular treatment, 10 genetic variants influencing methionine metabolism
      were analyzed. Pearson's chi(2) test and multinominal regression analysis were
      used to define the relevance of these genetic variants for the occurrence of WMC.
      In this patient sample, the occurrence of WMC was significantly predicted by the
      TT genotype of methylenetetrahydrofolate reductase c.677C>T (chi(2) = 8.67; p =
      0.013; df = 2), the AA genotype of methylenetetrahydrofolate reductase c.1298A>C
      (chi(2) = 13.5; p = 0.001; df = 2), and the GG genotype of transcobalamin 2
      c.776C>G (chi(2) = 19.73; p < 0.001), in addition to male gender (chi(2) = 11.95;
      p = 0.001). These data strengthen the hypothesis that MTX effects are influenced
      by methionine metabolism, which may offer new strategies to improve MTX-based
      therapies.

PMID- 18806230
TI  - Language and the modulation of impulsive aggression.
AB  - The current conceptualization of the functional anatomy of impulsive aggression
      relies on data largely derived from studies of animal models of defensive rage.
      However, animal models cannot account for the replicable findings of verbal
      impairments and abnormalities in the language processing regions of the brain,
      described in more recent studies of impulsive aggression in humans. The authors
      present an updated model of impulsive aggression that preserves the core
      defensive rage functional anatomy while implicating the brain regions associated
      directly and indirectly with language processing and their relationship to
      executive function as integral to the etiology, modulation, and treatment of
      impulsive aggression.

PMID- 18806231
TI  - Disrupted development of the dominant hemisphere following prenatal irradiation.
AB  - One hundred children, exposed prenatally to radiation after the Chernobyl nuclear
      power plant accident, and 50 nonexposed classmates were examined between the ages
      of 11 and 13 years old using neuropsychiatric tests, WISC, EEG, and visual evoked
      potentials. Individual prenatal radiation doses were reconstructed for all
      examined children. The exposed children were found to have more neuropsychiatric
      disorders, left-brain neurological signs, lower full-scale and verbal IQ, IQ
      discrepancies with verbal decrement, disorganized EEG patterns, an excess of
      lateralized-to-left frontotemporal region delta and beta power with depression of
      theta and alpha power, and interhemispheric inversion visual information
      processing. Mothers' mental health, stress, and prenatal irradiation contributed
      to these effects, along with several confounding factors.

PMID- 18806232
TI  - Preliminary evidence for sensitive periods in the effect of childhood sexual
      abuse on regional brain development.
AB  - Volumetric MRI scans from 26 women with repeated episodes of childhood sexual
      abuse and 17 healthy female comparison subjects (ages 18-22 years) were analyzed
      for sensitive period effects on hippocampal and amygdala volume, frontal cortex
      gray matter volume and corpus callosum area. Hippocampal volume was reduced in
      association with childhood sexual abuse at ages 3-5 years and ages 11-13 years.
      Corpus callosum was reduced with childhood sexual abuse at ages 9-10 years, and
      frontal cortex was attenuated in subjects with childhood sexual abuse at ages 14
      16 years. Brain regions have unique windows of vulnerability to the effects of
      traumatic stress.

PMID- 18806233
TI  - Hippocampal and amygdalar volumes in breast cancer survivors with posttraumatic
      stress disorder.
AB  - Although smaller hippocampi and amygdalae were found in cancer survivors with
      intrusions, associations between cancer-related posttraumatic stress disorder
      (PTSD) and these volumes are unknown. The authors performed MRI volumetric
      analyses of these regions in 15 cancer survivors with PTSD, 15 cancer survivors
      without PTSD, and 15 healthy comparison subjects. The authors also examined the
      correlation between PTSD symptom scores of the Impact of Event Scale and these
      volumes in the PTSD group. These volumes were not significantly different among
      the groups, but the intrusion score was inversely associated with the hippocampal
      volume. Results suggest intrusions, not PTSD diagnosis, might be associated with
      hippocampal volume.

PMID- 18806234
TI  - Cognitive dysfunctions associated with PTSD: evidence from World War II prisoners
      of war.
AB  - The authors aim to delineate cognitive dysfunction associated with posttraumatic
      stress disorder (PTSD) by evaluating a well-defined cohort of former World War II
      prisoners of war (POWs) with documented trauma and minimal comorbidities. The
      authors studied a cross-sectional assessment of neuropsychological performance in
      former POWs with PTSD, PTSD with other psychiatric comorbidities, and those with
      no PTSD or psychiatric diagnoses. Participants who developed PTSD had average IQ,
      while those who did not develop PTSD after similar traumatic experiences had
      higher IQs than average (approximately 116). Those with PTSD performed
      significantly less well in tests of selective frontal lobe functions and
      psychomotor speed. In addition, PTSD patients with co-occurring psychiatric
      conditions experienced impairment in recognition memory for faces. Higher IQ
      appears to protect individuals who undergo a traumatic experience from developing
      long-term PTSD, while cognitive dysfunctions appear to develop with or subsequent
      to PTSD. These distinctions were supported by the negative and positive
      correlations of these cognitive dysfunctions with quantitative markers of trauma,
      respectively. There is a suggestion that some cognitive decrements occur in PTSD
      patients only when they have comorbid psychiatric diagnoses.

PMID- 18806235
TI  - Predictors of abnormal involuntary movement in an african schizophrenia
      population.
AB  - As little is known about the risk factors for abnormal involuntary movements in
      African patients with schizophrenia, 170 Xhosa participants with schizophrenia
      were rated with the abnormal involuntary movement scale. Abnormal involuntary
      movements occurred in 19.4% of this group. Modeling of the data set showed that
      combining age at interview, age-squared, cannabis use or abuse, and anhedonia
      successfully identified 82.35% of cases of involuntary movements overall.
      Abnormal involuntary movements increased with increasing age (in a nonlinear
      manner), the presence of a cannabis use or abuse history seems to be protective
      against involuntary movements, and anhedonia is associated with the group that
      displayed fewer involuntary movements.

PMID- 18806236
TI  - beta-Amyloid is associated with reduced cognitive function in healthy older
      adults.
AB  - Though elevated beta-amyloid deposition is associated with Alzheimer's disease,
      recent evidence suggests beta-amyloid is elevated in healthy older adults prior
      to the onset of Alzheimer's disease. No study has yet investigated whether
      reduced cognitive function is related to beta-amyloid elevation in healthy older
      adults. Thirty-five healthy older adults underwent neuropsychological testing and
      fasting blood draw with subsequent serum beta-amyloid 1-40 level quantification.
      beta-amyloid was negatively correlated with several aspects of cognition.
      Findings indicate that beta-amyloid level is associated with cognitive function
      in healthy older adults in a pattern similar to early Alzheimer's disease.
      Further work investigating possible mechanisms is needed.

PMID- 18806237
TI  - Treatment for late-onset obsessive-compulsive disorder with parkinsonism.
AB  - Dysfunction of the basal ganglia and frontal subcortical structures occurs in
      both obsessive-compulsive disorder and parkinsonism. Treatment of obsessive
      compulsive disorder with parkinsonism is a therapeutic challenge, especially in
      old age as selective serotonin reuptake inhibitors may aggravate motor symptoms
      and worsen clinical conditions. The authors present a series of patients with
      late onset obsessive-compulsive disorder demonstrating improvement in obsessive
      compulsive disorder as well as parkinsonian signs.

PMID- 18806238
TI  - Apathy in dementia: clinical and sociodemographic correlates.
AB  - The authors examine prevalence and the sociodemographic and clinical correlates
      of apathy in dementia. Apathy was assessed in 121 outpatients in a behavioral
      neurology clinic using the Informant and Clinician versions of the Apathy
      Evaluation Scale (AES-I, AES-C). Apathy was found to be very prevalent across the
      dementias. Functional impairment, aberrant motor behavior, and irritability were
      associated with a greater likelihood of being apathetic upon evaluation with the
      AES-I. Additionally, with the AES-C, persons with dementia who lived with
      individuals other than their spouses were more likely to suffer apathy compared
      to those who lived with their spouses. These findings have clinical and research
      implications.

PMID- 18806239
TI  - Increased p50 gating but intact prepulse inhibition in borderline personality
      disorder.
AB  - The authors explore sensory gating deficits in borderline personality disorder
      patients, such as those described in schizophrenia, in patients with borderline
      personality disorder. Gating of the P50, N100, and P200 auditory evoked
      potentials and prepulse inhibition of the startle response (PPI) were measured in
      borderline patients and a group of healthy comparison subjects. Borderline
      patients did not show lower sensory gating, but showed higher P50, N100, and P200
      gating than comparison subjects. This was mainly due to the increased response
      after the first stimulus. There were no group differences in PPI. Unlike in other
      major psychiatric disorders, such as schizophrenia, sensory (motor) gating is
      intact in borderline personality disorder. The higher early preattentive and mid
      latency evoked potentials suggest a higher response tendency in borderline
      personality disorder, but this needs further replication.

PMID- 18806240
TI  - Depressed mood and memory impairment before and after unilateral posteroventral
      pallidotomy in Parkinson's disease.
AB  - This study evaluated poor mood state as a moderator of changes in verbal recall
      ability from before to after unilateral posteroventral pallidotomy in 54
      individuals with advanced Parkinson's disease. Repeated-measures analysis of
      covariance (controlling for motor disease severity) indicated that left
      posteroventral pallidotomy subjects with depressed mood performed more poorly on
      measures of verbal list learning and story recall compared to nondepressed
      subjects or right-posteroventral pallidotomy subjects with depressed mood both
      before and after surgery. The results suggest that depressed mood should be taken
      into account when interpreting memory test performance in Parkinson's disease
      surgical candidates both before and after surgery.

PMID- 18806241
TI  - Successful treatment of hallucinations associated with sensory impairment using
      gabapentin.
AB  - Sensory impairment hallucinations, such as visual hallucinations with visual
      loss, may not respond to traditional treatments such as antipsychotics. In this
      case series, the authors describe four patients with either visual or musical
      hallucinations associated with sensory impairment who were successfully treated
      with gabapentin.

PMID- 18806242
TI  - MK 801: a possible neuroprotective agent by poststroke depression?

PMID- 18806243
TI  - Alcoholic optic neuropathy: another complication of alcohol abuse.

PMID- 18806244
TI  - Management of phantom limb pain and sensation with milnacipran.

PMID- 18806245
TI  - Valproate-induced hyperammonemic encephalopathy without cognitive sequelae: a
      case report in the psychiatric setting.

PMID- 18806246
TI  - Central pontine myelinolysis as a complication of refeeding syndrome in a patient
      with anorexia nervosa.

PMID- 18806247
TI  - Psychosis in a case of schizophrenia and Parkinson's disease.

PMID- 18806248
TI  - Risperidone treatment of sleep disturbances in Tourette's syndrome.

PMID- 18806249
TI  - Charles bonnet syndrome: two case reports.

PMID- 18806250
TI  - Risperidone treatment of complex hallucinations in a patient with posterior
      cortical atrophy.

PMID- 18806251
TI  - ECT treatment for two cases of dementia-related pathological yelling.

PMID- 18806252
TI  - Failure to induce oral tolerance in mice is predictive of dietary allergenic
      potency among foods with sensitizing capacity.
AB  - Animal models are needed to assess novel proteins produced through biotechnology
      for potential dietary allergenicity. Currently proposed rodent models evaluate
      sensitizing potential of food extracts or proteins following parenteral
      administration or oral administration with adjuvant. However, food allergy
      requires not only the potential to induce immunoglobulin (Ig) E but also the
      capacity to avoid induction of oral tolerance (specific inhibition of IgE
      production). Here we describe a mouse model that assesses the potential of food
      extracts to induce oral tolerance. Adult C3H/HeJ mice were exposed orally to food
      extracts (without adjuvant) and subsequently challenged with the extract ip.
      Reduction of antigen-specific serum IgE relative to appropriate controls was used
      to indicate tolerance. Foods associated with persistent, severe allergy (peanut,
      Brazil nut), and nonallergens (turkey, spinach) were less tolerizing than foods
      associated with frequently resolving allergy (egg white). Digestibility was
      assessed in vitro, and pH alterations or encapsulation were used to modify
      solubility or digestibility. Egg white, peanut, and Brazil nut proteins were
      resistant to gastric enzyme (pepsin) degradation; turkey and spinach were not.
      Among pepsin-resistant proteins, peanut and Brazil nut appeared more sensitive to
      intestinal enzyme than egg white. For the extracts tested, full gastric digestion
      appeared to prevent induction of tolerance. Once through the stomach, only
      proteins resistant to intestinal enzymes induced tolerance. Limiting gastric
      digestion with sodium bicarbonate enhanced tolerance to peanut and Brazil nut.
      This model represents a complementary method of assessing potential
      allergenicity. Also, the conditions under which the test protein is encountered
      may impact experimental outcome.

PMID- 18806253
TI  - Deviant lifestyles and violent victimization at school.
AB  - This study examines how the lifestyles of juveniles influence violent
      victimization at school. Using data from the National Survey of Adolescents, this
      study demonstrates that both indirect victimization, through witnessing violence,
      and sexual and physical assaults of students are pervasive problems at schools.
      Although a number of individual and structural characteristics predict the risk
      of becoming a victim at school, the most consistent predictor of violent
      victimization is the juvenile's own deviant lifestyle. Those who participate in a
      deviant lifestyle substantially increase their odds of all three forms of
      victimization. Therefore, even within the relatively controlled setting of
      schools, juveniles who participate in deviant lifestyles are at a high risk for
      victimization.

PMID- 18806254
TI  - From the kitchen to the bedroom: frequency rates and consequences of sexual
      harassment among female domestic workers in Brazil.
AB  - Sexual harassment has been investigated mostly in developed countries. The
      authors examined frequency rates and consequences of sexual harassment among
      female domestic workers in Brazil. Twenty-six percent had been sexually harassed
      at work during the past year. Live-in workers were at significantly greater risk
      for experiencing sexual harassment than those residing in their own homes, when
      controlling for participants' age, race, and social class. Women residing in
      their employers' residences used more alcohol and drugs than their counterparts.
      Harassed women had significantly higher self-esteem impairment and anxiety and
      depression than nonharassed women. Nonharassed women residing in their own homes
      had the best physical well-being. Concerning participants' worst sexually
      harassing experiences, the perpetrators were likely to be men (75%), who also
      engaged in more severe types of sexual harassment than female perpetrators. The
      emotional reactions to such incidents were significantly more negative when
      perpetrated by men than by women. Implications for foreign in-home workers
      employed by Europeans and North Americans are discussed.

PMID- 18806256
TI  - A Monte Carlo method for calculating Bayesian uncertainties in internal
      dosimetry.
AB  - This paper presents a novel Monte Carlo method (WeLMoS, Weighted Likelihood Monte
      Carlo sampling method) that has been developed to perform Bayesian analyses of
      monitoring data. The WeLMoS method randomly samples parameters from continuous
      prior probability distributions and then weights each vector by its likelihood
      (i.e. its goodness of fit to the measurement data). Furthermore, in order to
      quality assure the method, and assess its strengths and weaknesses, a second
      method (MCMC, Markov chain Monte Carlo) has also been developed. The MCMC method
      uses the Metropolis algorithm to sample directly from the posterior distribution
      of parameters. The methods are evaluated and compared using an artificially
      generated case involving an exposure to a plutonium nitrate aerosol. In addition
      to calculating the uncertainty on internal dose, the methods can also calculate
      the probability distribution of model parameter values given the observed data.
      In other words, the techniques provide a powerful tool to obtain the estimates of
      parameter values that best fit the data and the associated uncertainty on these
      estimates. Current applications of the methodology, including the determination
      of lung solubility parameters, from volunteer and cohort data, are also
      discussed.

PMID- 18806255
TI  - The burden of mental disorders.
AB  - In the last decade, there has been an increase in interest in the burden of
      chronic and disabling health conditions that are not necessarily fatal, such as
      the mental disorders. This review systematically summarizes data on the burden
      associated with 11 major mental disorders of adults. The measures of burden
      include estimates of prevalence, mortality associated with the disorders,
      disabilities and impairments related to the disorders, and costs. This review
      expands the range of mental disorders considered in a report on the global burden
      of disease, updates the literature, presents information on the range and depth
      of sources of information on burden, and adds estimates of costs. The purpose is
      to provide an accessible guide to the burden of mental disorders, especially for
      researchers and policy makers who may not be familiar with this subfield of
      epidemiology.

PMID- 18806257
TI  - Isothermal titration calorimetry reveals differential binding thermodynamics of
      variable region-identical antibodies differing in constant region for a univalent
      ligand.
AB  - The classical view of immunoglobulin molecules posits two functional domains
      defined by the variable (V) and constant (C) regions, which are responsible for
      antigen binding and antibody effector functions, respectively. These two domains
      are thought to function independently. However, several lines of evidence
      strongly suggest that C region domains can affect the specificity and affinity of
      an antibody for its antigen (Ag), independent of avidity-type effects. In this
      study, we used isothermal titration calorimetry to investigate the thermodynamic
      properties of the interactions of four V region-identical monoclonal antibodies
      with a univalent peptide antigen. Comparison of the binding of IgG1, IgG2a,
      IgG2b, and IgG3 with a 12-mer peptide mimetic of Cryptococcus neoformans
      polysaccharide revealed a stoichiometry of 1.9-2.0 with significant differences
      in thermodynamic binding parameters. Binding of this peptide to the antibodies
      was dominated by favorable entropy. The interaction of these antibodies with
      biotinylated peptides manifested greater enthalpy than for native peptides
      indicating that biotin labeling affected the types of Ag-Ab complexes formed. Our
      results provide unambiguous thermodynamic evidence for the notion that the C
      region can affect the interaction of the V region with an Ag.

PMID- 18806258
TI  - Helicobacter pylori protein HP0175 transactivates epidermal growth factor
      receptor through TLR4 in gastric epithelial cells.
AB  - The pathophysiology of Helicobacter pylori-associated gastroduodenal diseases,
      ulcerogenesis, and carcinogenesis is intimately linked to activation of epidermal
      growth factor receptor (EGFR) and production of vascular endothelial growth
      factor (VEGF). Extracellular virulence factors, such as CagA and VacA, have been
      proposed to regulate EGFR activation and VEGF production in gastric epithelial
      cells. We demonstrate that the H. pylori secretory protein, HP0175, by virtue of
      its ability to bind TLR4, transactivates EGFR and stimulates EGFR-dependent VEGF
      production in the gastric cancer cell line AGS. Knock-out of the hp0175 gene
      attenuates the ability of the resultant H. pylori strain to activate EGFR or to
      induce VEGF production. HP0175-induced activation of EGFR is preceded by
      translocation of TLR4 into lipid rafts. In lipid rafts, the Src kinase family
      member Lyn interacts with TLR4, leading to tyrosine phosphorylation of TLR4.
      Knockdown of Lyn prevents HP0175-induced activation of EGFR and VEGF production.
      Tyrosine-phosphorylated TLR4 interacts with EGFR. This interaction is necessary
      for the activation of EGFR. Disruption of lipid rafts with methyl beta
      cyclodextrin prevents HP0175-induced tyrosine phosphorylation of TLR4 and
      activation of EGFR. This mechanism of transactivation of EGFR is novel and
      distinct from that of metalloprotease-dependent shedding of EGF-like ligands,
      leading to autocrine activation of EGFR. It provides new insight into our
      understanding of the receptor cross-talk network.

PMID- 18806259
TI  - Sustained activation of the tyrosine kinase Syk by antigen in mast cells requires
      local Ca2+ influx through Ca2+ release-activated Ca2+ channels.
AB  - Mast cell activation involves cross-linking of IgE receptors followed by
      phosphorylation of the non-receptor tyrosine kinase Syk. This results in
      activation of the plasma membrane-bound enzyme phospholipase Cgamma1, which
      hydrolyzes the minor membrane phospholipid phosphatidylinositol 4,5-bisphosphate
      to generate diacylglycerol and inositol trisphosphate. Inositol trisphosphate
      raises cytoplasmic Ca2+ concentration by releasing Ca2+ from intracellular
      stores. This Ca2+ release phase is accompanied by sustained Ca2+ influx through
      store-operated Ca2+ release-activated Ca2+ (CRAC) channels. Here, we find that
      engagement of IgE receptors activates Syk, and this leads to Ca2+ release from
      stores followed by Ca2+ influx. The Ca2+ influx phase then sustains Syk activity.
      The Ca2+ influx pathway activated by these receptors was identified as the CRAC
      channel, because pharmacological block of the channels with either a low
      concentration of Gd3+ or exposure to the novel CRAC channel blocker 3
      fluoropyridine-4-carboxylic acid (2',5'-dimethoxybiphenyl-4-yl)amide or RNA
      interference knockdown of Orai1, which encodes the CRAC channel pore, all
      prevented the increase in Syk activity triggered by Ca2+ entry. CRAC channels and
      Syk are spatially close together, because increasing cytoplasmic Ca2+ buffering
      with the fast Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic
      acid tetrakis failed to prevent activation of Syk by Ca2+ entry. Our results
      reveal a positive feedback step in mast cell activation where receptor-triggered
      Syk activation and subsequent Ca2+ release opens CRAC channels, and the ensuing
      local Ca2+ entry then maintains Syk activity. Ca2+ entry through CRAC channels
      therefore provides a means whereby the Ca2+ and tyrosine kinase signaling
      pathways can interact with one another.

PMID- 18806260
TI  - The chondroitin polymerase K4CP and the molecular mechanism of selective bindings
      of donor substrates to two active sites.
AB  - Bacterial chondroitin polymerase K4CP is a multifunctional enzyme with two active
      sites. K4CP catalyzes alternative transfers of glucoronic acid (GlcA) and N
      acetylgalactosamine (GalNAc) to elongate a chain consisting of the repeated
      disaccharide sequence GlcAbeta1-3GalNAcbeta1-4. Unlike the polymerization
      reactions of DNA and RNA and polypeptide synthesis, which depend upon templates,
      the monosaccharide polymerization by K4CP does not. To investigate the catalytic
      mechanism of this reaction, we have used isothermal titration calorimetry to
      determine the binding of the donor substrates UDP-GlcA and UDP-GalNAc to purified
      K4CP protein and its mutants. Only one donor molecule bound to one molecule of
      K4CP at a time. UDP-GlcA bound only to the C-terminal active site at a high
      affinity (K(d)=6.81 microm), thus initiating the polymerization reaction. UDP
      GalNAc could bind to either the N-terminal or C-terminal active sites at a low
      affinity (K(d)=266-283 microm) but not to both sites at the same time. The
      binding affinity of UDP-GalNAc to a K4CP N-terminal fragment (residues 58-357)
      was profoundly decreased, yielding the average K(d) value of 23.77 microm, closer
      to the previously reported K(m) value for the UDP-GalNAc transfer reaction that
      takes place at the N-terminal active site. Thus, the first step of the reaction
      appears to be the binding of UDP-GlcA to the C-terminal active site, whereas the
      second step involves the C-terminal region of the K4CP molecule regulating the
      binding of UDP-GalNAc to only the N-terminal active site. Alternation of these
      two specific bindings advances the polymerization reaction by K4CP.

PMID- 18806261
TI  - Hyaluronan binding to link module of TSG-6 and to G1 domain of aggrecan is
      differently regulated by pH.
AB  - The physiological functions of hyaluronan (HA) in the extracellular matrix of
      vertebrate tissues involve a range of specific protein interactions. In this
      study, the interaction of HA with the Link module from TSG-6 (Link_TSG6) and G1
      domain of aggrecan (G1), were investigated by a biophysical analysis of
      translational diffusion in dilute solution using confocal fluorescence recovery
      after photobleaching (confocal FRAP). Both Link_TSG6 and G1 were shown to bind to
      polymeric HA and these interactions could be competed with HA(8) and HA(10)
      oligosaccharides, respectively. Equilibrium experiments showed that the binding
      affinity of Link_TSG6 to HA was maximal at pH 6.0, and reduced dramatically above
      and below this pH. In contrast, G1 had maximum binding at pH 7.0-8.0 and moderate
      to strong binding affinity over a much broader pH range (5.5-8.0). The K(D)
      determined for Link_TSG6 binding to HA showed a 100-fold increase in binding
      affinity between pH 7.4 and 6.0, whereas G1 showed a 75-fold decrease in binding
      affinity over the same pH range. The sharp difference observed in their pH
      binding suggests that pH controls the physiological function of TSG-6, with a low
      affinity for HA at neutral pH, but with increased affinity as the pH falls below
      pH 7. TSG-6 and aggrecan interact with HA through structurally homologous domains
      and the difference in pH-dependent binding can be understood in terms of
      differences in the presence and topographical distribution of key regulatory
      amino acids in Link_TSG6 and in the related tandem Link domains in aggrecan G1.

PMID- 18806262
TI  - The p38 mitogen-activated protein kinase augments nucleotide excision repair by
      mediating DDB2 degradation and chromatin relaxation.
AB  - The p38 MAPK is a family of serine/threonine protein kinases that play important
      roles in cellular responses to external stress signals, e.g. UV irradiation. To
      assess the role of p38 MAPK pathway in nucleotide excision repair (NER), the most
      versatile DNA repair pathway, we determined the efficiency of NER in cells
      treated with p38 MAPK inhibitor SB203580 and found that p38 MAPK is required for
      the prompt repair of UV-induced DNA damage CPD. We further investigated the
      possible mechanism through which p38 MAPK regulates NER and found that p38 MAPK
      mediates UV-induced histone H3 acetylation and chromatin relaxation. Moreover,
      p38 MAPK also regulates UV-induced DDB2 ubiquitylation and degradation via
      phosphorylation of the target protein. Finally, our results showed that p38 MAPK
      is required for the recruitment of NER factors XPC and TFIIH to UV-induced DNA
      damage sites. We conclude that p38 MAPK regulates chromatin remodeling as well as
      DDB2 degradation for facilitating NER factor assembly.

PMID- 18806263
TI  - Integrin cross-talk in endothelial cells is regulated by protein kinase A and
      protein phosphatase 1.
AB  - In endothelial cells (ECs) beta1 integrin function-blocking antibodies inhibit
      alphavbeta3 integrin-mediated adhesion to a recombinant alpha4-laminin fragment
      (ralpha4LN fragment). beta1 integrin sequestration of talin is not the mechanism
      by which beta1 integrin modulates alphavbeta3 integrin ligand binding. Rather,
      treatment of the ECs with beta1 integrin function-blocking antibodies enhances
      cAMP-dependent protein kinase (PKA) activity and increases beta3 integrin serine
      phosphorylation. The PKA inhibitor H-89 abrogates the effect of beta1 integrin
      function-blocking antibodies on beta3 integrin serine phosphorylation and EC
      ralpha4LN fragment binding. beta3 integrin contains a serine residue at position
      752. To confirm the importance of this residue in alphavbeta3 integrin-ralpha4LN
      fragment binding, we mutated it to alanine (beta3S752A) or aspartic acid
      (beta3S752D). Chinese hamster ovary (CHO) cells expressing wild type or
      beta3S752A integrin attach robustly to ligand. CHO cells expressing beta3S752D
      integrin do not. Because the beta3 cytoplasmic tail lacks a PKA consensus site,
      it is unlikely that PKA acts directly on beta3 integrin. Instead, we have tested
      an hypothesis that PKA regulates beta3 integrin serine phosphorylation indirectly
      through phosphorylation of inhibitor-1, which, when phosphorylated, inhibits
      protein phosphatase 1 (PP1). Treatment of ECs with beta1 integrin function
      blocking antibodies significantly increases phosphorylation of inhibitor-1.
      Furthermore, blocking PP1 activity pharmacologically inhibits alphavbeta3
      mediated cell adhesion to the ralpha4LN fragment when both PKA and beta1 integrin
      function are inhibited. Concomitantly, there is an increase in serine
      phosphorylation of the beta3 integrin cytoplasmic tail. These results indicate a
      novel mechanism by which beta1 integrin negatively modulates alphavbeta3 integrin
      ligand binding via activation of PKA and inhibition of PP1 activity.

PMID- 18806264
TI  - Adsorption of follicular dendritic cell-secreted protein (FDC-SP) onto mineral
      deposits. Application of a new stable gene expression system.
AB  - Follicular dendritic cell-secreted protein (FDC-SP) is a small secretory protein
      having structural similarities to statherin, a protein in saliva thought to play
      a role in calcium retention in saliva. In contrast, FDC-SP is thought to play a
      role in the immune system associated with germinal centers. We report here the
      very specific expression of FDC-SP in junctional epithelium at the gingival
      crevice. This region is very important for the host defense against pathogens and
      for periodontal protection. To be able to better understand the function of FDC
      SP, we developed a novel gene expression system that exploited gene trapping and
      site-specific gene integration to introduce the protein into a mammalian cell
      culture system. Using this system we were able to express FDC-SP as a fusion
      protein with green fluorescent protein in an osteogenic progenitor cell line with
      long term stability, which we then used to find that the fusion protein
      specifically adsorbs onto mineral deposits and the surface of hydroxyapatite
      particles exogenously added to the culture. This adsorption was highly dependent
      on the structural integrity of FDC-SP. These results suggest that FDC-SP may play
      an important role, adsorbing onto the surface of cementum and alveolar bone
      adjacent to periodontal ligament and onto tooth surface at the gingival crevice.

PMID- 18806266
TI  - Galectin-3 regulates integrin alpha2beta1-mediated adhesion to collagen-I and 
      IV.
AB  - Galectins are a taxonomically widespread family of galactose-binding proteins of
      which galectin-3 is known to modulate cell adhesion. Using single cell force
      spectroscopy, the contribution of galectin-3 to the adhesion of Madin-Darby
      canine kidney (MDCK) cells to different extracellular matrix proteins was
      investigated. When adhering to collagen-I or -IV, some cells rapidly entered an
      enhanced adhesion state, marked by a significant increase in the force required
      for cell detachment. Galectin-3-depleted cells had an increased probability of
      entering the enhanced adhesion state. Adhesion enhancement was specific to
      integrin alpha(2)beta(1), as it was not observed when cells adhered to
      extracellular matrix substrates by other integrins. The adhesion phenotype of
      galectin-3-depleted cells was mimicked in a galactoside-deficient MDCK cell line
      and could be complemented by the addition of recombinant galectin-3. We propose
      that galectin-3 influences integrin alpha(2)beta(1)-mediated adhesion complex
      formation by altering receptor clustering.

PMID- 18806265
TI  - Multiple protein domains mediate interaction between Bcl10 and MALT1.
AB  - Bcl10 and MALT1 are essential mediators of NF-kappaB activation in response to
      the triggering of a diverse array of transmembrane receptors, including antigen
      receptors. Additionally, both proteins are translocation targets in MALT
      lymphoma. Thus, a detailed understanding of the interaction between these
      mediators is of considerable biological importance. Previous studies have
      indicated that a 13-amino acid region downstream of the Bcl10 caspase recruitment
      domain (CARD) is responsible for interacting with the immunoglobulin-like domains
      of MALT1. We now provide evidence that the death domain of MALT1 and the CARD of
      Bcl10 also contribute to Bcl10-MALT1 interactions. Although a direct interaction
      between the MALT1 death domain and Bcl10 cannot be detected via
      immunoprecipitation, FRET data strongly suggest that the death domain of MALT1
      contributes significantly to the association between Bcl10 and MALT1 in T cells
      in vivo. Furthermore, analysis of point mutants of conserved residues of Bcl10
      shows that the Bcl10 CARD is essential for interaction with the MALT1 N terminus.
      Mutations that disrupt proper folding of the Bcl10 CARD strongly impair Bcl10
      MALT1 interactions. Molecular modeling and functional analyses of Bcl10 point
      mutants suggest that residues Asp(80) and Glu(84) of helix 5 of the Bcl10 CARD
      directly contact MALT1. Together, these data demonstrate that the association
      between Bcl10 and MALT1 involves a complex interaction between multiple protein
      domains. Moreover, the Bcl10-MALT1 interaction is the second reported example of
      interactions between a CARD and a non-CARD protein region, which suggests that
      many signaling cascades may utilize CARD interactions with non-CARD domains.

PMID- 18806267
TI  - Differential activation of ERK and Rac mediates the proliferative and anti
      proliferative effects of hyaluronan and CD44.
AB  - Hyaluronan, a widely distributed component of the extracellular matrix, exists in
      a high molecular weight (native) form and lower molecular weight form (HMW- and
      LMW-HA, respectively). These different forms of hyaluronan bind to CD44 but
      elicit distinct effects on cellular function. A striking example is the opposing
      effects of HMW- and LMW-HA on the proliferation of vascular smooth muscle cells;
      the binding of HMW-HA to CD44 inhibits cell cycle progression, whereas the
      binding of LMW-HA to CD44 stimulates cell cycle progression. We now report that
      cyclin D1 is the primary target of LMW-HA in human vascular smooth muscle cells,
      as it is for HMW-HA, and that the opposing cell cycle effects of these CD44
      ligands result from differential regulation of signaling pathways to cyclin D1.
      HMW-HA binding to CD44 selectively inhibits the GTP loading of Rac and Rac
      dependent signaling to the cyclin D1 gene, whereas LMW-HA binding to CD44
      selectively stimulates ERK activation and ERK-dependent cyclin D1 gene
      expression. These data describe a novel mechanism of growth control in which a
      ligand-receptor system generates opposing effects on mitogenesis by
      differentially regulating signaling pathways to a common cell cycle target. They
      also emphasize how a seemingly subtle change in matrix composition can have a
      profound effect on cell proliferation.

PMID- 18806268
TI  - Role of the Per/Arnt/Sim domains in ligand-dependent transformation of the aryl
      hydrocarbon receptor.
AB  - The aryl hydrocarbon receptor (AhR) mediates the toxic and biological effects of
      2,3,7,8-tetrachlorodibenzo-p-dioxin and related compounds. In a process termed
      transformation, ligand binding converts the AhR into its high affinity DNA
      binding form that represents a dimer of the AhR and Arnt, a closely related
      nuclear protein. During transformation, protein chaperone Hsp90 is thought to be
      replaced by Arnt in overlapping binding sites in the basic helix loop helix and
      PASB domains of the AhR. Here, analysis of AhR variants containing a modified
      PASB domain and AhR PASA-PASB fragments of various lengths revealed (i) an
      inhibitory effect on transformation concomitant with Hsp90 binding in the PASB
      domain, (ii) an ability of the PASA-PASB fragment of the AhR to reproduce key
      steps in the transformation process, and (iii) a ligand-dependent conformational
      change in the PASA domain consistent with increased PASA exposure during AhR
      transformation. Based on these results, we propose a new mechanism of AhR
      transformation through initiation of Arnt dimerization and Hsp90 displacement in
      AhR PASA/B domains. This study provides insights into mechanisms of AhR
      transformation, dimerization of PAS domain proteins, and Hsp90 dissociation in
      activation of its client proteins.

PMID- 18806269
TI  - Can sugars be produced from fatty acids? A test case for pathway analysis tools.
AB  - MOTIVATION: In recent years, several methods have been proposed for determining
      metabolic pathways in an automated way based on network topology. The aim of this
      work is to analyse these methods by tackling a concrete example relevant in
      biochemistry. It concerns the question whether even-chain fatty acids, being the
      most important constituents of lipids, can be converted into sugars at steady
      state. It was proved five decades ago that this conversion using the Krebs cycle
      is impossible unless the enzymes of the glyoxylate shunt (or alternative
      bypasses) are present in the system. Using this example, we can compare the
      various methods in pathway analysis. RESULTS: Elementary modes analysis (EMA) of
      a set of enzymes corresponding to the Krebs cycle, glycolysis and gluconeogenesis
      supports the scientific evidence showing that there is no pathway capable of
      converting acetyl-CoA to glucose at steady state. This conversion is possible
      after the addition of isocitrate lyase and malate synthase (forming the
      glyoxylate shunt) to the system. Dealing with the same example, we compare EMA
      with two tools based on graph theory available online, PathFinding and Pathway
      Hunter Tool. These automated network generating tools do not succeed in
      predicting the conversions known from experiment. They sometimes generate
      unbalanced paths and reveal problems identifying side metabolites that are not
      responsible for the carbon net flux. This shows that, for metabolic pathway
      analysis, it is important to consider the topology (including bimolecular
      reactions) and stoichiometry of metabolic systems, as is done in EMA.
      SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
      online.

PMID- 18806270
TI  - Expression and secretion of N-acylethanolamine-hydrolysing acid amidase in human
      prostate cancer cells.
AB  - N-acylethanolamines (NAEs) are a class of bioactive lipid molecules in animal
      tissues, including the endocannabinoid anandamide and the anti-inflammatory
      substance N-palmitoylethanolamine. Enzymatic hydrolysis of NAEs is considered to
      be an important step to regulate their endogenous levels. Lysosomal NAE
      hydrolysing acid amidase (NAAA) as well as fatty acid amide hydrolase (FAAH) is
      responsible for this reaction. Here, we report relatively high expression of NAAA
      in human prostate cancer cells (PC-3, DU-145 and LNCaP) and prostate epithelial
      cells (PrEC), with the highest mRNA level in LNCaP cells. FAAH and the NAE
      forming enzyme N-acylphosphatidylethanolamine-hydrolysing phospholipase D (NAPE
      PLD) were also detected in these cells. NAAA activity in LNCaP cells could be
      distinguished from coexisting FAAH activity, based on their different pH
      dependency profiles and specific inhibition of FAAH activity by URB597. These
      results showed that both the enzymes were functionally active. We also found that
      NAAA was partly secreted from LNCaP cells, which underlined possible usefulness
      of this enzyme as a biomarker of prostate cancer.

PMID- 18806271
TI  - Role of the aromatic residues in the near-amino terminal motif of vimentin in
      intermediate filament assembly in vitro.
AB  - Type III and IV intermediate filament (IF) proteins share a conserved sequence
      motif of -Tyr-Arg-Arg-X-Phe- at the near-amino termini. To characterize
      significance of the aromatic residues in the motif, we prepared vimentin mutants
      in which Tyr-10 and Phe-14 are substituted with Asn and Ser (Vim[Y10N], Vim[F14S]
      and Vim[Y10N, F14S]), and examined assembly properties in vitro by electron
      microscopy and viscosity measurements. At 2 s after initiation of assembly
      reaction at pH 7.2 and 150 mM NaCl, all the vimentin mutants formed so-called
      unit-length filaments (ULFs) that were slightly larger than ULFs of wild-type
      vimentin. In following filament elongation, Vim[Y10N, F14S] and Vim[Y10N]
      performed longitudinal annealing of ULFs very rapidly and formed IFs within only
      2.5 and 5 min, respectively, while Vim[F14S] and wild-type vimentin gave IFs by
      40-60 min. The IFs of Vim[Y10N, F14S] and Vim[Y10N], however, tended to
      intertwine each other and formed bundles in parts of the specimens. The
      intertwinements decreased as the salt concentration decreased, and optimal salt
      concentration for the two mutants to form normal IFs was 50 mM. These results
      suggest that the aromatic residues, especially Tyr-10, in the motif have a role
      in controlling intermolecular interactions involved in IF assembly in vitro and
      suppress undesirable filament intertwinements at physiological ionic strength.

PMID- 18806273
TI  - Mitochondrial DNA background modulates the assembly kinetics of OXPHOS complexes
      in a cellular model of mitochondrial disease.
AB  - Leber's hereditary optic neuropathy (LHON), the most frequent mitochondrial
      disorder, is mostly due to three mitochondrial DNA (mtDNA) mutations in
      respiratory chain complex I subunit genes: 3460/ND1, 11778/ND4 and 14484/ND6.
      Despite considerable clinical evidences, a genetic modifying role of the mtDNA
      haplogroup background in the clinical expression of LHON remains experimentally
      unproven. We investigated the effect of mtDNA haplogroups on the assembly of
      oxidative phosphorylation (OXPHOS) complexes in transmitochondrial hybrids
      (cybrids) harboring the three common LHON mutations. The steady-state levels of
      respiratory chain complexes appeared normal in mutant cybrids. However, an
      accumulation of low molecular weight subcomplexes suggested a complex I
      assembly/stability defect, which was further demonstrated by reversibly
      inhibiting mitochondrial protein translation with doxycycline. Our results showed
      differentially delayed assembly rates of respiratory chain complexes I, III and
      IV amongst mutants belonging to different mtDNA haplogroups, revealing that
      specific mtDNA polymorphisms may modify the pathogenic potential of LHON
      mutations by affecting the overall assembly kinetics of OXPHOS complexes.

PMID- 18806272
TI  - Copy number variations and risk for schizophrenia in 22q11.2 deletion syndrome.
AB  - 22q11.2 Deletion Syndrome (22q11.2DS) is a common microdeletion syndrome with
      congenital and late-onset features. Testing for the genomic content of copy
      number variations (CNVs) may help elucidate the 22q11.2 deletion mechanism and
      the variable clinical expression of the syndrome including the high (25%) risk
      for schizophrenia. We used genome-wide microarrays to assess CNV content and the
      parental origin of 22q11.2 deletions in a cohort of 100 adults with 22q11.2DS (44
      with schizophrenia) and controls. 22q11.2DS subjects with schizophrenia failed to
      exhibit de novo CNVs or any excess of novel inherited CNVs outside the 22q11.2
      region. There were no significant effects of parental origin of the 22q11.2
      deletion, deletion length, parental age or family history on expression of
      schizophrenia. There was no evidence for a general increase of de novo CNVs in
      22q11.2DS. A novel finding was the relative paucity of males with de novo 22q11.2
      deletions of paternal origin (P = 0.019). The Y chromosome may play a mediating
      role in the mechanism of 22q11.2 deletion events during spermatogenesis,
      resulting in the previously observed excess of maternal de novo 22q11.2
      deletions. Hemizygosity of the 22q11.2 region appears to be the major CNV-related
      risk factor for schizophrenia in 22q11.2DS. The results reinforce the need for
      further efforts to identify specific molecular mechanisms underlying this
      expression and to identify the 1% of patients with schizophrenia who carry
      22q11.2 deletions.

PMID- 18806274
TI  - WFS1 mutations are frequent monogenic causes of juvenile-onset diabetes mellitus
      in Lebanon.
AB  - Most cases of juvenile-onset diabetes (JOD) are diagnosed as type 1 diabetes
      (T1D), for which genetic studies conducted in outbred Caucasian populations
      support the concept of multifactorial inheritance. However, this view may be
      partly challenged in particular population settings. In view of the suggestive
      evidence for a high prevalence of Wolfram syndrome (WFS) in Lebanon, the
      phenotypic variability associated with WFS1 mutations, and the high consanguinity
      rate in Lebanon, we aimed to evaluate the contribution of WFS1 mutations as
      monogenic determinants to JOD in Lebanon. We performed a family-based genetic
      study, with linkage analysis followed by systematic mutation screening of WFS1
      exons in all JOD probands. The study population consisted of an unbiased
      recruitment of all juvenile-onset insulin-dependent diabetic patients from a
      specialized diabetes pediatric clinic in Beirut, Lebanon. Homozygous or compound
      heterozygous WFS1 mutations were found in 22 of the 399 JOD probands (5.5%),
      resulting in WFS (17 probands) or in non-syndromic non-autoimmune diabetes
      mellitus (DM, five probands). These accounted for 12.1% (21/174) of probands in
      consanguineous families, compared with 0.4% (1/225) in non-consanguineous
      families. Of the 38 patients identified with homozygous or compound heterozygous
      WFS1 mutations, 11 (29%) had non-syndromic DM, all of whom carried a particular
      WFS1 mutation, WFS1(LIB), encoding a protein with an extended C-terminal domain.
      This mutation resulted in a delayed onset or absence of extrapancreatic features.
      These results underscore the major impact of population-specific factors, such as
      population-specific mutations and founder effects, and family structure in the
      genetic determinism of JOD.

PMID- 18806275
TI  - hnRNP H enhances skipping of a nonfunctional exon P3A in CHRNA1 and a mutation
      disrupting its binding causes congenital myasthenic syndrome.
AB  - In humans and great apes, CHRNA1 encoding the muscle nicotinic acetylcholine
      receptor alpha subunit carries an inframe exon P3A, the inclusion of which yields
      a nonfunctional alpha subunit. In muscle, the P3A(-) and P3A(+) transcripts are
      generated in a 1:1 ratio but the functional significance and regulation of the
      alternative splicing remain elusive. An intronic mutation (IVS3-8G>A), identified
      in a patient with congenital myasthenic syndrome, disrupts an intronic splicing
      silencer (ISS) and results in exclusive inclusion of the downstream P3A exon. We
      found that the ISS-binding splicing trans-factor was heterogeneous nuclear
      ribonucleoprotein (hnRNP) H and the mutation attenuated the affinity of hnRNP for
      the ISS approximately 100-fold. We next showed that direct placement of hnRNP H
      to the 3' end of intron 3 silences, and siRNA-mediated downregulation of hnRNP H
      enhances recognition of exon P3A. Analysis of the human genome suggested that the
      hnRNPH-binding UGGG motif is overrepresented close to the 3' ends of introns.
      Pursuing this clue, we showed that alternative exons of GRIP1, FAS, VPS13C and
      NRCAM are downregulated by hnRNP H. Our findings imply that the presence of the
      hnRNP H-binding motif close to the 3' end of an intron is an essential but
      underestimated splicing regulator of the downstream exon.

PMID- 18806276
TI  - Platelet-derived growth factor BB stimulates vasculogenesis of embryonic stem
      cell-derived endothelial cells by calcium-mediated generation of reactive oxygen
      species.
AB  - AIMS: Platelet-derived growth factor BB (PDGF-BB) has been assigned a critical
      role in vascular growth and recruitment of perivascular mural cells. The purpose
      of the present study is to investigate the signalling events underlying the
      stimulation of vasculogenesis of mouse embryonic stem (ES) cells by PDGF-BB.
      METHODS AND RESULTS: PDGF-BB increased vascular sprouting and branching of
      capillary-like structures in embryoid bodies as evaluated by computer-assisted
      analysis of CD31-positive cell structures. It also activated extracellular
      regulated kinase 1,2 (ERK1,2) and c-Jun N-terminal kinase but not p38 mitogen
      activated protein kinase or PI 3-kinase. Microfluorometric analysis of fluo-4
      fluorescence revealed that treatment with PDGF-BB raised intracellular Ca(2+)
      levels in differentiating ES cells expressing the PDGF receptor beta, an effect
      that was abolished in the presence of the intracellular Ca(2+) chelator BAPTA.
      Furthermore, PDGF-BB raised reactive oxygen species (ROS) levels in embryoid
      bodies as evaluated using the redox-sensitive dye H(2)DCF-DA. ROS generation was
      blunted in the presence of the NADPH oxidase inhibitors diphenylen iodonium (DPI)
      and apocynin as well as in the presence of BAPTA, suggesting that ROS generation
      is regulated by intracellular Ca(2+) transients. The stimulation of
      vasculogenesis of ES cells upon treatment with PDGF-BB was significantly
      inhibited by the ERK1,2 inhibitor U0126, the NADPH oxidase inhibitors DPI,
      apocynin, 4-(2-aminoethyl)benzenesulfonylfluoride and VAS2870, the free radical
      scavengers vitamin E, and N-(2-mercaptopropionyl)glycin as well as by BAPTA.
      CONCLUSION: Our data demonstrate that the pro-vasculogenic effects of PDGF-BB are
      mediated by Ca(2+)-induced ROS generation, resulting in the activation of an
      ERK1,2-mediated signal transduction cascade.

PMID- 18806277
TI  - Transgenic myocardial overexpression of prokineticin receptor-2 (GPR73b) induces
      hypertrophy and capillary vessel leakage.
AB  - AIMS: Prokineticins are small secreted bioactive molecules. They exert their
      biological activity by binding to two G protein-coupled receptors. Previously, we
      have shown that the overexpression of prokineticin receptor-1 (PKR1) in
      transgenic (TG) mouse hearts induced neovascularization. Since PKR1 and PKR2 are
      85% identical and expressed in cardiovascular tissues, we hypothesized that PKR2
      may also contribute to cardiomyocyte growth and vascularization. METHODS AND
      RESULTS: We have generated TG mice overexpressing PKR2 in cardiomyocytes. TG mice
      exhibit increased hypertrophic gene expression and heart-to-body weight ratio
      accompanied by an increased length of cardiomyocytes at the age of 12 weeks.
      Increased left ventricular end-systolic and diastolic diameters without cardiac
      dysfunction at the age of 24 weeks indicate that TG mice have an eccentric
      hypertrophy with compensated cardiac function. Quantitative morphological
      analysis showed that TG hearts have a normal microvessel density and number of
      branch points. However, they exhibit increased abnormal endothelial cell shape
      and ultrastructure, changed cellular distribution of a tight junction protein
      zona occludens-1 (ZO-1), and vascular leakage in heart without a rise of
      angiogenic factor levels at early and late age. The application of media
      conditioned by H9c2 cardioblast cells overexpressing PKR2 significantly induced
      impaired ZO-1 localization in H5V endothelial cells, mimicking the TG model.
      CONCLUSION: These findings provide the first genetic evidence that cardiomyocyte
      PKR2 signalling leads to eccentric hypertrophy in an autocrine regulation and
      impaired endothelial integrity in a paracrine regulation without inducing
      angiogenesis. These TG mice may provide a new genetic model for heart diseases.

PMID- 18806278
TI  - A comparison of foetal and infant mortality in the United States and Canada.
AB  - BACKGROUND: Infant mortality rates are higher in the United States than in
      Canada. We explored this difference by comparing gestational age distributions
      and gestational age-specific mortality rates in the two countries. METHODS:
      Stillbirth and infant mortality rates were compared for singleton births at
      >or=22 weeks and newborns weighing>or=500 g in the United States and Canada (1996
      2000). Since menstrual-based gestational age appears to misclassify gestational
      duration and overestimate both preterm and postterm birth rates, and because a
      clinical estimate of gestation is the only available measure of gestational age
      in Canada, all comparisons were based on the clinical estimate. Data for
      California were excluded because they lacked a clinical estimate. Gestational age
      specific comparisons were based on the foetuses-at-risk approach. RESULTS: The
      overall stillbirth rate in the United States (37.9 per 10,000 births) was similar
      to that in Canada (38.2 per 10,000 births), while the overall infant mortality
      rate was 23% (95% CI 19-26%) higher (50.8 vs 41.4 per 10,000 births,
      respectively). The gestational age distribution was left-shifted in the United
      States relative to Canada; consequently, preterm birth rates were 8.0 and 6.0%,
      respectively. Stillbirth and early neonatal mortality rates in the United States
      were lower at term gestation only. However, gestational age-specific late
      neonatal, post-neonatal and infant mortality rates were higher in the United
      States at virtually every gestation. The overall stillbirth rates (per 10,000
      foetuses at risk) among Blacks and Whites in the United States, and in Canada
      were 59.6, 35.0 and 38.3, respectively, whereas the corresponding infant
      mortality rates were 85.6, 49.7 and 42.2, respectively. CONCLUSIONS: Differences
      in gestational age distributions and in gestational age-specific stillbirth and
      infant mortality in the United States and Canada underscore substantial
      differences in healthcare services, population health status and health policy
      between the two neighbouring countries.

PMID- 18806279
TI  - Ability of antibodies to two new caliciviral vaccine strains to neutralise feline
      calicivirus isolates from the UK.
AB  - This study examined a panel of 110 UK field isolates of feline calicivirus (FCV)
      for susceptibility to cross-neutralisation by a panel of eight antisera raised in
      cats infected with FCV strains F9, 255, FCVG1 and FCV431. The pairs of antisera
      raised against F9 or 255, neutralised 20 and 21 per cent or 37 and 56 per cent of
      field strains of virus respectively. In contrast, the pairs of antisera raised
      against the newer vaccine strains FCVG1 or FCV431 neutralised 29 and 70 per cent
      or 67 and 87 per cent of field strains respectively. Antisera raised against the
      two newer strains, namely FCVG1 and FCV431, neutralised a greater proportion of
      field strains of calicivirus than antisera raised against the older FCV vaccine
      strains F9 and 255.

PMID- 18806280
TI  - Outbreak of bovine tuberculosis featuring anergy to the skin test, udder lesions
      and milkborne disease in young calves.
AB  - A severe outbreak of bovine tuberculosis in a 1300-head, multisite dairy herd in
      Great Britain had several unusual features, including anergy to the tuberculin
      skin test, milkborne disease in calves and a farm cat, and a risk of human
      infection. The outbreak was controlled by culling 221 cattle over 15 months, by
      using the gamma-interferon (gamma-IFN) test and by the examination of milk
      samples. The gamma-IFN test detected infected animals that were not detected by
      the skin test.

PMID- 18806281
TI  - Prevalence of four enteropathogens in the faeces of young diarrhoeic dairy calves
      in Switzerland.
AB  - The prevalences of Cryptosporidium parvum, rotavirus, bovine coronavirus (BCV),
      and enterotoxigenic Escherichia coli (E coli K99) were determined in diarrhoeic
      dairy calves aged one to 21 days on 71 dairy farms in western Switzerland during
      the winter of 2005 to 2006. Faecal samples from 147 untreated calves suffering
      from acute diarrhoea were analysed by standardised diagnostic methods, and the
      immunoglobulin status of each calf was evaluated. The prevalences of C parvum,
      rotavirus, BCV and E coli k99 were 55.0 per cent, 58.7 per cent, 7.8 per cent and
      5.5 per cent, respectively. The proportions of herds positive for the respective
      pathogens among the herds with diarrhoeic calves were 41.7 per cent, 52.1 per
      cent, 2.1 per cent and 2.1 per cent. The immunoglobulin concentration in the
      serum of 90.5 per cent of the diarrhoeic calves was below 8 g/l.

PMID- 18806282
TI  - Veterinary public health: medical and veterinary general practitioner research
      priorities in Scotland.

PMID- 18806283
TI  - Prevalence of antibodies to canine respiratory coronavirus in some dog
      populations in Japan.

PMID- 18806284
TI  - Cytological features of mandibular actinomycotic osteomyelitis in a cow.

PMID- 18806285
TI  - Haemoglobin A1c testing for dogs with diabetes.

PMID- 18806286
TI  - Ban on swill feeding.

PMID- 18806287
TI  - Bluetongue control strategy.

PMID- 18806288
TI  - Bluetongue control strategy.

PMID- 18806289
TI  - Phosphatidylinositol 3 kinase pathway and 4-hydroxy-2-nonenal-induced oxidative
      injury in the RPE.
AB  - PURPOSE: 4-Hydroxy-2-nonenal (4-HNE) is a major lipid peroxidation product in the
      retina and the retinal pigment epithelium. The purpose of the present study was
      to investigate how NF-E2-related factor-2 (Nrf2) and phosphatidylinositol 3
      (PI3K) pathways affect the responses of cultured human retinal pigment epithelial
      (RPE) cells to 4-HNE. METHODS: Cultured ARPE-19 cells were treated with different
      concentrations of 4-HNE and a PI3K inhibitor, LY294002. Intracellular glutathione
      (GSH) was measured by high-performance liquid chromatography (HPLC). The
      transcriptional activity of Nrf2 was measured by dual luciferase assay after
      transient transfection with reporter plasmids. The mRNA level of glutamate
      cysteine ligase (GCL) was quantified by real-time RT-PCR. Formation of HNE adduct
      on heat shock cognate protein 70 (Hsc70) was measured by immunoprecipitation and
      Western blot analyses. RESULTS: Treatment with 4-HNE increased Nrf2 activity and
      GSH synthesis in a dose-dependent manner in cultured RPE cells. The modulatory
      subunit of GCL was upregulated by 4-HNE. Antioxidant responses were largely
      abolished by pretreatment with LY294002. The modification of Hsc70 by 4-HNE was
      increased when PI3K was inhibited. CONCLUSIONS: The Nrf2-dependent antioxidant
      response protects against 4-HNE toxicity, and this protective mechanism is
      dependent on the functions of the PI3K pathway.

PMID- 18806290
TI  - Lipoprotein particles of intraocular origin in human Bruch membrane: an unusual
      lipid profile.
AB  - PURPOSE: Throughout adulthood, Bruch membrane (BrM) accumulates esterified
      cholesterol (EC) associated with abundant 60- to 80-nm-diameter lipoprotein-like
      particles (LLP), putative apolipoprotein B (apoB) lipoproteins secreted by the
      retinal pigment epithelium (RPE). In the present study, neutral lipid,
      phospholipids, and retinoid components of human BrM-LLP were assayed. METHODS:
      Particles isolated from paired choroids of human donors were subjected to
      comprehensive lipid profiling (preparative liquid chromatography [LC] gas
      chromatography [GC]), thin-layer chromatography (TLC), high-performance liquid
      chromatography (HPLC), Western blot analysis, and negative stain electron
      microscopy. Results were compared to plasma lipoproteins isolated from
      normolipemic volunteers and to conditioned medium from RPE-J cells supplemented
      with palmitate to induce particle synthesis and secretion. RESULTS: EC was the
      largest component (32.4+/-7.9 mol%) of BrM-LLP lipids. EC was 11.3-fold more
      abundant than triglyceride (TG), unlike large apoB lipoproteins in plasma. Of the
      fatty acids (FA) esterified to cholesterol, linoleate (18:2n6) was the most
      abundant (41.7+/-4.7 mol%). Retinyl ester (RE) was detectable at picomolar levels
      in BrM-LLP. Notably scarce in any BrM-LLP lipid class was the photoreceptor
      abundant FA docosahexaenoate (DHA, 22:6n3). RPE-J cells synthesized apoB and
      numerous EC-rich spherical particles. CONCLUSIONS: BrM-LLP composition resembles
      plasma LDL more than it does photoreceptors. An EC-rich core is possible for
      newly synthesized lipoproteins as well as those processed in plasma. Abundant EC
      could contribute to a transport barrier in aging and lesion formation in age
      related maculopathy (ARM). Analysis of BrM-LLP composition has revealed new
      aspects of retinal cholesterol and retinoid homeostasis.

PMID- 18806291
TI  - Circulating hematopoietic stem cells in patients with idiopathic choroidal
      neovascularization.
AB  - PURPOSE: In a prior study, the correlation was investigated between circulating
      hematopoietic stem cells (HSCs) and the activity or severity of choroidal
      neovascularization (CNV) in patients with age-related macular degeneration (AMD).
      The present study was designed to explore the role of circulating HSCs in the
      pathogenesis of CNV in patients with idiopathic (i)CNV. METHODS: Thirteen
      patients with clinically documented iCNV and 10 age-sex matched patients without
      iCNV or systemic disease were enrolled in a case-control study. Circulating HSCs
      were collected from the patients' peripheral blood and cultured. Colony-forming
      capacity, migration activity, and invasion activity of HSCs were experimentally
      analyzed. RESULTS: Colony-forming units by Hill's assay (CFU-Hill) were markedly
      lower (P<0.001) in patients with iCNV (12.8+/-3.2) than in healthy patients
      (67.6+/-12.6). Invasion activities of HSCs were reduced significantly in patients
      with iCNV. CFU-Hill was impaired in the patients (4.0+/-1.2) with CNV more than
      1500 microm compared with the patients (20.3+/-4.0) with CNV less than 1500
      microm (P=0.006). CONCLUSIONS: Similar to the previous finding of CNV associated
      with AMD, impaired functional activities of circulating HSCs were observed in
      patients with iCNV, which correlated with the size of iCNV. These results in
      young patients provide evidence to support the role of circulating HSCs in the
      pathogenesis of CNV.

PMID- 18806293
TI  - Analysis of rare variants in the complement component 2 (C2) and factor B (BF)
      genes refine association for age-related macular degeneration (AMD).
AB  - PURPOSE: Several single-nucleotide polymorphisms (SNPs) in the C2 and BF genes
      have been associated with age-related macular degeneration (AMD) in Caucasian
      populations from the United States. The study was conducted to evaluate whether
      these SNPs are also associated with AMD in persons of Anglo-Celtic ethnicity in
      an Australian population. METHODS: Included in the study were 565 persons with
      AMD and 204 ethnically matched control subjects. All participants completed a
      standard health questionnaire, were given a fundus examination, and provided a
      blood sample for DNA extraction. Alleles were determined by a matrix-assisted
      desorption ionization-time of flight (MALDI-TOF)-based approach followed by
      statistical analysis. RESULTS: The C2 and BF genes indicated significant
      association with AMD of only two SNPs; rs547154 (IVS10) in the C2 gene (P=9.1 x
      10(-5)) and rs641153 (R32Q) in the BF gene (P=7.0 x 10(-5)). No association with
      AMD was found for SNP rs9332739 (E318D) in the C2 gene or for rs4151667 (L9H),
      rs1048709 (R150R), rs4151659 (K565E), or rs2072633 (IVS17) in the BF gene. A
      protective haplotype of variants IVS10 and R32Q was associated with AMD (OR 0.29,
      95% CI 0.20-0.42). CONCLUSIONS: In this study, the association of the IVS10 and
      R32Q variants in the C2 and BF genes in AMD was replicated. Haplotype analysis
      indicated association of these variants with AMD in an Australian population.
      Both IVS10 and R32Q variants were in strong linkage disequilibrium with each
      other (r(2)=0.96). Although the E318D and L9H variants have shown association
      with AMD in previous studies, the findings were not in agreement. This
      demonstrates a refined pattern of association of these rare variants with AMD.

PMID- 18806292
TI  - Remodeling of the connective tissue microarchitecture of the lamina cribrosa in
      early experimental glaucoma.
AB  - PURPOSE: To characterize the trabeculated connective tissue microarchitecture of
      the lamina cribrosa (LC) in terms of total connective tissue volume (CTV),
      connective tissue volume fraction (CTVF), predominant beam orientation, and
      material anisotropy in monkeys with early experimental glaucoma (EG). METHODS:
      The optic nerve heads from three monkeys with unilateral EG and four bilaterally
      normal monkeys were three dimensionally reconstructed from tissues perfusion
      fixed at an intraocular pressure of 10 mm Hg. A three-dimensional segmentation
      algorithm was used to extract a binary, voxel-based representation of the porous
      LC connective tissue microstructure that was regionalized into 45 subvolumes, and
      the following quantities were calculated: total CTV within the LC, mean and
      regional CTVF, regional predominant beam orientation, and mean and regional
      material anisotropy. RESULTS: Regional variation within the laminar
      microstructure was considerable within the normal eyes of all monkeys. The
      laminar connective tissue was generally most dense in the central and superior
      regions for the paired normal eyes, and laminar beams were radially oriented at
      the periphery for all eyes considered. CTV increased substantially in EG eyes
      compared with contralateral normal eyes (82%, 44%, 45% increases; P<0.05), but
      average CTVF changed little (-7%, 1%, and -2% in the EG eyes). There were more
      laminar beams through the thickness of the LC in the EG eyes than in the normal
      controls (46%, 18%, 17% increases). CONCLUSIONS: The substantial increase in
      laminar CTV with little change in CTVF suggests that significant alterations in
      connective and nonconnective tissue components in the laminar region occur in the
      early stages of glaucomatous damage.

PMID- 18806294
TI  - The functional consequences of glaucoma for eye-hand coordination.
AB  - PURPOSE: To examine whether patients with glaucoma exhibit differences in
      visually guided reaching-and-grasping (prehension) behavior compared with
      normally sighted control subjects. METHODS: Sixteen patients with glaucoma and 16
      control subjects with no ocular disease participated. Participants were required
      to reach out and precision grasp one of two cylindrical objects placed on a table
      top in front of them in laboratory conditions in three viewing conditions
      (binocular, right eye alone, left eye alone). Lightweight reflective markers were
      placed on the subject's preferred hand for recording its movement in three
      dimensional space. Three motion capture units recorded the motion of these
      markers as the subjects reached out and precision grasped household objects.
      Various indices of prehension planning, execution, and control were quantified.
      Visual fields (VF) were measured using standard automated perimetry generating
      monocular mean deviation (MD) scores. Binocular VF sensitivity was estimated by
      using the integrated visual field (IVF). Stereoacuity was measured with the
      Frisby stereoacuity test. Significant differences in prehension movement between
      patients and control subjects in each viewing condition were investigated, and
      associations between prehension kinematics and VF sensitivity were examined.
      RESULTS: The patients and control subjects were of a similar age (median [range]:
      patient group, 72.2 years [62.5-86.9]; control group, 69.0 years [64.3-78.3]).
      The patient group had asymmetrical disease and relatively minor binocular
      overlapping defects (better eye MD, -5.7 dB [-16.7 to +0.45 dB]; worse eye MD, 
      11.8 dB [-29.3 to -1.5 dB]; IVF score, 3 [0-36]). They exhibited slightly poorer
      stereoacuity levels than did the control subjects (patient group, 55 sec arc [40
      110]; control group, 40 sec arc [20-80; Mann-Whitney U test, P < 0.05]). They
      also showed statistically significant delays in average movement onset (MO:
      approximately 100 ms delay, Mann-Whitney U test P < 0.0001) and overall movement
      time (OMD: approximately 140 ms delay; Mann-Whitney U test P < 0.05), suggesting
      impairments in initial movement planning and control. Deficits were exhibited in
      the reaching component, with data suggesting that glaucomatous patients made more
      tentative movements when reaching for the object. These deficits correlated with
      both increasing severity of VF defect and impaired stereoacuity. There were no
      differences in grasping characteristics between patients and control subjects in
      this sample. CONCLUSIONS: This study provides evidence that patients with
      glaucoma exhibit deficits in eye-hand coordination compared with the age-matched
      normally sighted control. Further study is needed to assess the specific effect
      of field loss location on prehension kinematics.

PMID- 18806295
TI  - Microplasmin: ex vivo characterization of its activity in porcine vitreous.
AB  - PURPOSE: Microplasmin is a recombinant protein limited to the enzymatic moiety of
      plasmin without any of its cringle domains. Its enzymatic activity is similar to
      that of plasmin enzyme. The present study characterizes in a porcine eye model
      the vitreolytic ability of microplasmin. METHOD: Freshly harvested porcine eyes
      were used in these trials. Eyes were injected with escalating doses of
      microplasmin (62.5, 125, 250, 400 microg) for 1 hour or with 125 microg
      microplasmin with increasing time exposures (15, 30, 60, 120 minutes). Eyes were
      fixed by a very slow dehydration process to preserve the integrity of the
      vitreous retinal interface. They were examined by light microscopy to determine
      the degree of posterior vitreous detachment and by scanning electron microscopy
      (SEM) to study structural changes. RESULTS: Effective separation of the posterior
      hyaloid appeared to be dose dependent. After 1 hour, the posterior pole was
      detached in 100% of porcine eyes exposed to 125 microg microplasmin and in the
      midperiphery to 250 microg microplasmin. Vitreous at the ora did not detach. At
      120 minutes of exposure, midperipheral detachment was observed with 125 microg
      microplasmin. A smooth retinal surface was seen where the enzyme caused posterior
      vitreous detachment. There was also significant change to the integrity of the
      vitreous without any obvious structural alterations to the retina by histology or
      scanning electron microscopy. CONCLUSIONS: Microplasmin caused vitreolysis and
      posterior vitreous separation in an ex vivo porcine eye model in an apparent dose
      and time-dependent fashion. In this model system, the minimal effective dose
      appeared to be 125 microg.

PMID- 18806296
TI  - Suppression of retinal peroxisome proliferator-activated receptor gamma in
      experimental diabetes and oxygen-induced retinopathy: role of NADPH oxidase.
AB  - PURPOSE: Recently, the authors have shown that NADPH oxidase is positively
      correlated with increased leukocyte adhesion and vascular leakage in diabetes and
      neovascularization in oxygen-induced retinopathy (OIR). Peroxisome proliferator
      activated receptor gamma (PPARgamma) agonists have been shown to prevent vascular
      inflammation and leakage in an experimental model of diabetes. The goal of this
      study was to investigate whether there is a link between NADPH oxidase and
      PPARgamma that leads to vascular dysfunction in diabetic retina or OIR. METHODS:
      Diabetes was induced with streptozotocin in wild-type mice or NOX2 knockout mice.
      One group of wild-type mice was treated with apocynin. Bovine retinal endothelial
      cells (BRECs) were treated with normal glucose (5 mM) or high glucose (25 mM) in
      the presence or absence of superoxide dismutase (SOD) or NADPH oxidase inhibitors
      (apocynin or diphenyleneiodonium [DPI]). Western blotting and immunofluorescence
      were used to evaluate PPARgamma expression. Activation of nuclear factor
      (NF)kappaB was measured using the transcription factor assay kit and Western blot
      analysis of phospho-NFkappaB. PPARgamma expression was also tested in OIR and
      lipopolysaccharide-induced retinal inflammation. RESULTS: Retinal expression of
      PPARgamma was suppressed in experimental models of diabetes, OIR, and retinal
      inflammation. This was associated with the activation of NFkappaB in the diabetic
      retina. These effects were prevented by apocynin or deletion of NOX2. PPARgamma
      expression was also suppressed in endothelial cells treated with high glucose,
      and this was prevented by apocynin, DPI, and SOD. CONCLUSIONS: Suppression of
      PPARgamma is involved in the pathogenesis of diabetic retinopathy and OIR. NADPH
      oxidase could be an upstream mediator of these changes.

PMID- 18806297
TI  - Further assessment of the complement component 2 and factor B region associated
      with age-related macular degeneration.
AB  - PURPOSE: Polymorphic variation in genes involved in regulation of the complement
      system has been implicated as a major cause of genetic risk, in addition to the
      LOC387715/HTRA1 locus and other environmental influences. Previous studies have
      identified polymorphisms in the complement component 2 (CC2) and factor B (CFB)
      genes, as potential functional variants associated with AMD, in particular CFB
      R32Q and CC2 rs547154, both of which share strong linkage disequilibrium (LD).
      METHODS: Data derived from the HapMap Project were used to select 18 haplotype
      tagging SNPs across the extended CC2/CFB region for genotyping, to measure the
      strength of LD in 318 patients with neovascular AMD and 243 age-matched control
      subjects to identify additional potential functional variants in addition to
      those originally reported. RESULTS: Strong LD was measured across this region as
      far as the superkiller viralicidic activity 2-like gene (SKIV2L). Nine SNPs were
      identified to be significantly associated with the genetic effect observed at
      this locus. Of these, a nonsynonymous coding variant SKIV2L R151Q (rs438999; OR,
      0.48; 95% confidence interval [CI], 0.31-0.74; P<0.001), was in strong LD with
      CFB R32Q, rs641153 (r(2)=0.95) and may exert a functional effect. When assessed
      within a logistic regression model measuring the effects of genetic variation at
      the CFH and LOC387715/HTRA1 loci and smoking, the effect remained significant
      (OR, 0.38; 95% CI, 0.22-0.65; P<0.001). Additional variation identified within
      this region may also confer a weaker but independent effect and implicate
      additional genes within the pathogenesis of AMD. CONCLUSIONS: Because of the high
      level of LD within the extended CC2/CFB region, variation within SKIV2L may exert
      a functional effect in AMD.

PMID- 18806298
TI  - Retinal gene expression and Muller cell responses after branch retinal vein
      occlusion in the rat.
AB  - PURPOSE: In a rat model of branch retinal vein occlusion (BRVO), changes in gene
      expression of factors implicated in the development of retinal edema and
      alterations in the properties of Muller cells were determined. METHODS: In adult
      Long-Evans rats, BRVO was induced by laser photocoagulation of retinal veins;
      untreated eyes served as controls. The mRNA levels of after factors were
      determined with real-time RT-PCR in the neural retina and retinal pigment
      epithelium after 1 and 3 days of BRVO: VEGF-A, pigment epithelium-derived factor
      (PEDF), tissue factor, prothrombin, the potassium channel Kir4.1, and aquaporins
      1 and 4. Potassium currents were recorded in isolated Muller cells, and cellular
      swelling was assessed in retinal slices. RESULTS: In the neural retina, the
      expression of VEGF was upregulated within 1 day of BRVO and returned to the
      control level after 3 days. PEDF was upregulated in the neuroretina and retinal
      pigment epithelium after 3 days of BRVO. Prothrombin, Kir4.1, and both aquaporins
      were downregulated in the neuroretina. After BRVO, Muller cells displayed a
      decrease in their potassium currents and an altered distribution of Kir4.1
      protein, an increase in the size of their somata, and cellular swelling under
      hypoosmotic stress that was not observed in control tissues. CONCLUSIONS: BRVO
      results in a rapid transient increase in the expression of VEGF and a delayed
      increase in the expression of PEDF. The downregulation of Kir4.1 and aquaporins,
      the mislocation of Kir4.1 protein, and the osmotic swelling of Muller cells may
      contribute to the development of edema and neuronal degeneration.

PMID- 18806299
TI  - Stimulation of specific cytokines in human conjunctival epithelial cells by
      defensins HNP1, HBD2, and HBD3.
AB  - PURPOSE: To investigate the effect of human defensins HNP1, HBD2, and HBD3 on
      human conjunctival epithelial cell cytokine secretion. METHODS: HNP1, HBD2, and
      HBD3 were used to test cytotoxicity (1-50 microg/mL) and to stimulate (1-20
      microg/mL) primary cultured and immortalized human conjunctival epithelial (IOBA
      NHC) cells. Cytokine concentrations in the culture medium were measured by
      cytokine array and a multiplexed microbead analysis. Protein kinase activation
      was determined by Western blot analysis after defensin stimulation and with
      specific inhibitors. RESULTS: HBD3, but not HNP1 or HBD2, killed more than 50% of
      IOBA-NHC cells at concentrations greater than 12.5 microg/mL. Only IL-6, IL-8,
      and RANTES were detected in the culture medium in the absence of defensins. All
      three cytokines increased in the presence of HNP1, HBD2, and HBD3 at
      concentrations of 5 to 20 microg/mL and between 2 and 8 hours and further
      accumulated at 24 hours Stimulation with HBD2 and HBD3 increased the secretion of
      IL-2 and MIP-1beta in IOBA-NHC cells but only of MIP-1beta in primary cultured
      cells. Activation of p42/44 mitogen-activated protein (MAP) kinase, Akt, and
      STAT3 was observed in primary and IOBA-NHC cells after defensin stimulation.
      Cytokine secretion was significantly decreased by the inhibition of p42/44 MAPK
      in IOBA-NHC cells. CONCLUSIONS: HNP and HBD selectively increase the secretion of
      specific proinflammatory cytokines in conjunctival epithelial cells in a time-
      and concentration-dependent manner, suggesting a supporting role to the innate
      immune system of the ocular surface.

PMID- 18806300
TI  - Diversity versus concentration in antipsychotic drug selection.
AB  - BACKGROUND: It is unknown to what extent providers utilize the full range of
      available antipsychotic agents, or tend to prescribe just a few with which they
      are familiar. AIMS OF THE STUDY: This study uses the Herfindahl index to measure
      the degree to which antipsychotic prescribing is diverse or concentrated within
      medical centers in the Department of Veterans Affairs. METHODS: Patients with
      schizophrenia who received prescriptions for antipsychotic medications from the
      Department of Veterans Affairs in fiscal year 2005 were identified. For each
      facility, the proportion of prescriptions that were written for each
      antipsychotic medication was computed. The Herfindahl index, which is defined as
      the sum of the square of the proportionate shares of each medication (i.e., 50%
      squared = 0.25), was computed for each facility, and its distribution across
      facilities was examined. RESULTS: We identified 785,485 prescriptions for
      antipsychotic medications across 76,787 patients within 128 facilities. With 7
      drugs to choose from (first-generation antipsychotics were not differentiated as
      separate drugs), the Herfindahl could range from 0.14 (if the drugs were
      prescribed equally) to 1 (if only 1 drug was prescribed to all patients). The
      Herfindahl averaged 0.20 to 0.21 and ranged from 0.16 to 0.31 across facilities.
      DISCUSSION: The Herfindahl index is a useful metric for describing the degree to
      which providers use a range of antipsychotic medications in treating patients
      with schizophrenia and suggests that VA facilities use a diversity of agents,
      thus taking advantage of the potentially unique drug-patient matches.
      IMPLICATIONS FOR HEALTH CARE PROVISION: The extent to which providers tailor
      their choice of antipsychotic medication to the particular characteristics of the
      patient may lead to better quality of care. IMPLICATIONS FOR HEALTH POLICIES: The
      fact that providers do use a range of antipsychotic medications suggests that
      formulary policies should not reduce access to these drugs. IMPLICATIONS FOR
      FURTHER RESEARCH: Further research is needed to construct physician-level
      measures of prescribing diversity and to examine whether clinical outcomes are
      improved when providers use a wider range of medications in their practice.

PMID- 18806301
TI  - Demand response of mental health services to cost sharing under managed care.
AB  - BACKGROUND: Higher demand-side cost sharing on mental health services than on
      general health services has been justified in economic terms because the demand
      response for mental health services has been found to be higher under traditional
      indemnity plans, and the welfare loss associated with insurance is higher while
      the risk spreading benefits were similar. The empirical studies of demand
      response for mental health services under fee-for-service health care delivery
      systems provide the supporting evidence. With the ascendance of managed care, the
      context in which demand-side cost sharing is imposed today differs from the
      context in which most of the empirical literature rests due to the presence of
      managed care. The economics of parity under managed care needs to be under re
      examination. AIMS OF THE STUDY: This study measures demand response of mental
      health services to cost-sharing under managed health care and compares it to
      demand response under traditional indemnity plans. METHODS: The 1996 Medical
      Expenditure Panel Survey (MEPS) data are used because this is the only year in
      which sufficient detail is available on coverage and forms of insurance in order
      to make the desired comparison. To address the selection problem, we focus on
      employees (and their dependents) who are privately insured and who have no choice
      of health plan. Couples with more than one insurance plan are also excluded from
      the analysis. We use logit models to analyze the effect of prices on the
      probability of any ambulatory mental health uses. We compare the estimated demand
      response to demand-side cost sharing between managed care plans and non-managed
      care plans by examining how demand prices affect the likelihood of seeking mental
      health services. RESULTS: In the range observed, deductibles have no significant
      impact on the likelihood of utilization for either indemnity or managed care
      plans. The coinsurance rate has a significant negative effect on seeking mental
      health services under indemnity plans. The effect of the coinsurance rate on
      demand under managed care plans is significantly smaller than that under
      indemnity plans and not significantly different from zero. Managed care itself
      decreases rates of utilization. DISCUSSION: Results in this study are consistent
      with the findings from the literature on mental health parity. The evidence
      suggests that mental health utilization is controlled by management under managed
      care and not primarily by out of pocket prices paid by consumers. Limitations
      include the small number of HMO enrollees and the current method can not entirely
      eliminate a concern about selection bias. IMPLICATION FOR HEALTH POLICY:
      Efficiency argument against parity of benefits for mental health care may not
      apply to managed care settings. At the same time, parity may accomplish less than
      mental health parity advocacy groups expect under managed care in terms of
      increasing access. IMPLICATION FOR FURTHER RESEARCH: Managed care continues to
      evolve, take many forms, and uses a number of rationing devices. It is important
      to conduct studies to isolate the effects of the components of managed care on
      utilization among different patient groups.

PMID- 18806302
TI  - Cost-effectiveness of group psychotherapy for depression in Uganda.
AB  - BACKGROUND: Low and middle-income countries are increasingly acknowledging the
      potential health and economic benefits associated with treatment of depression.
      To aid countries in making resource-allocation decisions, there is a need for
      cost-effectiveness analysis of treatments for depression in developing countries.
      Although there are a limited number of studies from developing countries that
      report data on treatment efficacy and costs, these data can be leveraged to
      tailor mathematical models that are used to evaluate the cost-effectiveness of
      depression treatments in specific settings. AIMS OF THE STUDY: Using data from
      depression studies in the published literature, as well as two studies in Uganda,
      we developed a decision-analytic model to evaluate the cost-effectiveness of
      group psychotherapy in the setting of Uganda. METHODS: We developed a Markov
      cohort model of depression and evaluated the health benefits and costs associated
      with group psychotherapy with and without booster sessions for recurrent
      depressive episodes. We synthesized published data on the epidemiology of
      depression, treatment efficacy, and costs to parameterize our model, and used
      data from developing countries where available. Outcomes included quality
      adjusted life expectancy (QALY), lifetime costs, and incremental cost
      effectiveness ratios (ICER). Costs were expressed in international dollars (I$)
      to facilitate comparisons across settings and studies. RESULTS: In Uganda, group
      psychotherapy without booster sessions decreased average number of depressive
      episodes by 6.2%, compared to no intervention; with booster sessions, reduction
      in number of episodes increased to 15.8%. Although group psychotherapy alone was
      less costly than psychotherapy with booster sessions, the ICER was higher, and
      therefore, group psychotherapy without booster sessions was dominated. The ICER
      associated with psychotherapy with booster sessions was I$ 1,150 per QALY,
      compared to no intervention. Although higher than previously published cost
      effectiveness estimates of treatments for depression, HIV and cardiovascular
      disease in the developing world, the ICER of psychotherapy with booster sessions
      falls below Uganda's per-capita GDP, a suggested threshold for cost
      effectiveness. The results were most sensitive to cost of the booster sessions
      and health state utility for depression. DISCUSSION: Our results suggest that
      group psychotherapy treatment with booster sessions for recurrent depressive
      episodes may be cost-effective in developing countries such as Uganda. These
      findings can assist in a global campaign for developing countries to provide and
      upscale appropriate depression treatment programs. However, there are only a
      limited number of studies on treatments for depression in the developing world
      with small numbers of enrolled subjects; most inputs to our Markov model relied
      on data from developed countries. Cultural, political, economic, and social
      differences between countries may limit the generalizability of our findings.
      IMPLICATIONS FOR HEALTH CARE PROVISION AND USE: This study suggests a promising
      role for group psychotherapy in treating depression. Integration of this service
      into primary care may result in cost-effective treatment for depression.
      IMPLICATIONS FOR HEALTH POLICIES: In developing countries with limited health
      care budgets, group psychotherapy can be a cost-effective treatment option for
      patients with depression. IMPLICATIONS FOR FURTHER RESEARCH: There are a limited
      number of clinical studies evaluating efficacy and costs of treatments for
      depression in developing countries. Research on depression in such settings can
      further assist in providing accurate and country-contextualized estimates of cost
      effectiveness.

PMID- 18806303
TI  - Cost-saving effects of olanzapine as long-term treatment for bipolar disorder.
AB  - BACKGROUND: Promoters of new medications often argue that using newer drug can
      reduce use of non-drug medical services and therefore reduce total healthcare
      spending. This cost-offset argument is plausible both in theory and in practice,
      but rigorous research on specific drugs or drug categories is needed to make
      targeted and efficient policy and management decisions. AIMS OF THE STUDY: I
      examined the drug-offset hypothesis for bipolar disorder, an important yet under
      studied clinical condition where effective medication treatments can service as
      substitutes for non-drug medical treatments. I compared two first line long-term
      treatments, a new atypical antipsychotic medication, olanzapine, and a
      traditional mood stabilizer, lithium. METHODS: I used private sector insurance
      claims data collected from a nationally representative sample of U.S. health
      plans between January 1998 and December 2001. I first selected a cohort of
      patients with bipolar disorder who were continuously enrolled for at least two
      years. I then used a propensity-score method to match individuals taking each
      drug on observed variables that are known to affect medication choices. The
      central challenge for estimation is that drug treatments are not randomly
      assigned among patients with bipolar disorder. To identify a causal link between
      choice of drugs and non-drug medical spending, I employed three different
      advanced econometrics techniques to assess the robustness of findings; namely
      interrupted time series, differencing strategies, and an instrumental variables
      approach. RESULTS: I found that compared to similar lithium users, olanzapine
      users spent approximately $330 more on monthly average non-drug medical services
      during the first year after initiation of drug treatment. The higher spending for
      olanzapine users was accounted for by both higher rates of re-hospitalization and
      more outpatient visits. In addition, olanzapine cost $153 per month while lithium
      cost $16 per month. Including the direct cost of the drugs, compared to similar
      patients taking lithium, patients with bipolar disorder taking olanzapine spent
      $5,600 more annually on health care services. DISCUSSION: These findings do not
      support the hypothesis that new drugs "pay for themselves" by reducing the need
      for other health care services in the case of olanzpine for bipolar disorder.
      This does not mean that the new drug is not "cost-effective" because increased
      "benefits" associated with the drug in terms of the improved quality of life may
      be worth the increased costs. However the findings do indicate that "cost
      offsets" must be measured and not taken for granted. Incorporating such drug
      offset evidence into policy and business decisions can facilitate appropriate
      clinical practices and improve efficiency of resource allocation. The methods
      used in this study to test for cost-offsets can be applied to other clinical
      areas and drug classes.

PMID- 18806304
TI  - Suppression of influenza A virus nuclear antigen production and neuraminidase
      activity by a nutrient mixture containing ascorbic acid, green tea extract and
      amino acids.
AB  - Influenza, one of the oldest and most common infections, poses a serious health
      problem causing significant morbidity and mortality, and imposing substantial
      economic costs. The efficacy of current drugs is limited and improved therapies
      are needed. A unique nutrient mixture (NM), containing ascorbic acid, green tea
      extract, lysine, proline, N-acetyl cysteine, selenium among other micronutrients,
      has been shown to exert anti-carcinogenic and anti-atherogenic activity both in
      vitro and in vivo. Many of the constituents of NM have been shown to have an
      inhibitory effect on replication of influenza virus and HIV. This prompted us to
      study the effect of NM on influenza A virus multiplication in infected cells and
      neuraminidase activity (NA) in virus particles. Addition of NM to Vero or MDCK
      cells post infection resulted in dose-dependent inhibition of viral nucleoprotein
      (NP) production in infected cells. NM-mediated inhibition of viral NP was
      selective and not due to cytotoxicity towards host cells. This antiviral effect
      was enhanced by pretreatment of virus with the nutrient mixture. Individual
      components of NM, namely ascorbic acid and green tea extract, also blocked viral
      NP production, conferring enhanced inhibition when tested in combination.
      Incubation of cell-free virus with NM resulted in dose-dependent inhibition of
      associated NA enzyme activity. In conclusion, the nutrient mixture exerts an
      antiviral effect against influenza A virus by lowering viral protein production
      in infected cells and diminishing viral enzymatic activity in cell-free
      particles.

PMID- 18806305
TI  - Antidiabetic potential of Citrus sinensis and Punica granatum peel extracts in
      alloxan treated male mice.
AB  - An investigation on the effects of four different concentrations of peel extract
      from Citrus sinensis (CS) or Punica granatum (PG) in male mice revealed the
      maximum glucose lowering and antiperoxidative activities at 25 mg/kg of CS and
      200 mg/kg of PG. In a separate experiment their potential was evaluated with
      respect to the regulation of alloxan induced diabetes mellitus. While a single
      dose of alloxan (120 mg/kg) increased the serum levels of glucose and alpha
      amylase activity, rate of water consumption and lipid peroxidation (LPO) in
      hepatic, cardiac and renal tissues with a parallel decrease in serum insulin
      level, administration of 25 mg/kg of CS or 200 mg/kg of PG was found to normalize
      all the adverse changes induced by alloxan, revealing the antidiabetic and anti
      peroxidative potential of test fruit peel extracts. Subsequent phytochemical
      analysis indicated that the high content of total polyphenols in the test peels
      might be related to the antidiabetic and antiperoxidative effects of the test
      peels.

PMID- 18806306
TI  - Mulberry leaves protect rat tissues from immobilization stress-induced
      inflammation.
AB  - The ability of the antioxidants in the mulberry leaves to protect Sprague-Dawley
      rats from injuries caused by immobilization stress was studied as an indicator of
      the tissue bioavailability of antioxidants. Nitrite level, lipid peroxidation and
      total antioxidant activity (TAA) in the plasma and tissues were measured. There
      were hypertrophy of the adrenal glands and kidneys, significant increased levels
      of nitrite in the plasma and adrenal glands, elevated thiobarbituric acid
      reactive substances (TBARS) in the plasma, kidneys and spleen, and a reduction of
      TAA in the plasma, liver, adrenal glands, kidneys and spleen of the immobilized
      rats. Antioxidants in the mulberry leaf extract suppressed the increase of
      nitrite and TBARS. Adrenal glands appeared to be the target organ of the
      antioxidants in the leaf extract. The low dose mulberry antioxidants were more
      effective than pure rutin (4 mg/day) to protect the cells against inflammation
      and peroxidation induced by stress.

PMID- 18806307
TI  - Effects of Coenzyme Q10 on TNF-alpha secretion in human and murine monocytic cell
      lines.
AB  - Studies in humans and cell culture as well as bioinformatics suggested that
      Coenzyme Q(10) (CoQ10) functions as an anti-inflammatory molecule. Here we
      studied the influence of CoQ10 (Kaneka Q10) on secretion of the pro-inflammatory
      cytokine tumor necrosis factor-alpha (TNF-alpha) by using the human and murine
      monocytic cell lines THP-1 and RAW264.7 expressing human apolipoprotein E3
      (apoE3) or pro-inflammatory apoE4. Incubation of cells with physiological (0.1-10
      microM) and supra-physiological (> 10 to < 100 microM) concentrations of CoQ10
      led to an intracellular accumulation of its reduced form without any cytotoxic
      effects. Stimulation of cell models with lipopolysaccharide (LPS) resulted in a
      substantially release of TNF-alpha. When THP-1 cells were pre-incubated with 10
      microM CoQ10, the LPS-induced TNF-alpha release was significantly decreased to 72
      +/- 32%. This effect is similar to those obtained by 10 microM N-Acetyl-Cysteine,
      a well known reference antioxidant. In RAW264.7-apoE3 and -apoE4 cells,
      significant reductions of LPS-induced TNF-alpha secretion to 73.3 +/- 2.8% and
      74.7 +/- 8.9% were found with 2.5 microM and 75 microM CoQ10, respectively. In
      conclusion, CoQ10 has moderate anti-inflammatory effects in two monocytic cell
      lines which could be mediated by its antioxidant activity.

PMID- 18806308
TI  - Antioxidative and cytoprotective effects of Artemisia capillaris fractions.
AB  - The antioxidant effects of Artemisia capillaris fractions against reactive oxygen
      species (ROS) were evaluated by measuring scavenging activities against 1,1
      diphenyl-2-picrylhydrazyl (DPPH) radical, superoxide (O_2(-)), hydroxyl (HO.) and
      nitric oxide (NO.) radical. Among five solvent fractions, ethyl acetate fraction
      showed the highest total polyphenol and total flavonoid contents as 648.75 and
      89.09 microg/mg, respectively. Also, the ethyl acetate fraction showed the
      highest scavenging activity; the 50% inhibitory concentration (IC50, microg/mg)
      value for DPPH, O_2(-), HO. and NO. radical scavenging were 4.76, 31.54, 69.34
      and 74.63, respectively. Additionally, the highest inhibition of rat liver
      microsomal lipid peroxidation was observed by ethyl acetate fraction. Except for
      free radical-mediated protein damage, ethyl acetate fraction showed the highest
      scavenging activity. The effect of Artemisia capillaris fractions on cell
      viability and DNA damage induced by H2O2 in Raw 264.7 cell were also evaluated by
      MTT and comet assay, respectively. The protective effect of ethyl acetate
      fraction, as indicated by cell viability increasing 71% and DNA breakage
      decreasing 51% as compared with H2O2-treated positive control. These results
      suggest that ethyl acetate fraction possess significant ROS scavenging and
      protective effect against oxidative DNA damage.

PMID- 18806309
TI  - Oxidation of glutathione and superoxide generation by inorganic and organic
      selenium compounds.
AB  - The carcinostatic activities of selenium (Se) compounds have been shown to be
      composition and concentration dependent. Several studies have indicated that the
      ratios between glutathione (GSH) and Se may play an important role in Se
      catalysis and toxicity. The present study examined the catalytic effect of three
      selenium compounds on GSH oxidation using lucigenin-dependent chemiluminescence
      (CL) as an indirect measure of superoxide generation. Various GSH:Se ratios were
      assayed for the glutathione oxidase activity of selenite, selenocystamine and
      diselenodipropionic acid. CL emitted from the reaction of selenite with GSH
      increased more rapidly and was greater than those from the diselenides, but the
      diselenide CL reactions were sustainable. Both selenite- and diselenide-induced
      CL were markedly suppressed by superoxide dismutase (SOD). Iodoacetic acid (IAc)
      effectively inhibited CL generated from selenite-, selenocystamine- and
      diselenodipropionic acid-catalyzed GSH oxidation. These results suggest that GSH
      oxidation catalyzed by selenite, and the diselenides selenocystamine and
      diselenodipropionic acid, generated the superoxide radical in which the CL was
      inhibited by SOD. Furthermore, CL inhibition by IAc suggests that the catalytic
      species producing superoxide were the GSSe(-) or RSe(-) anion. This redox
      chemistry may be responsible for selenite and organoselenium toxicity and
      apoptosis, making possible the design and synthesis of organoselenium-containing
      pharmaceuticals.

PMID- 18806310
TI  - Pregnenolone and dexamethasone, modulators of cytochrome P450-3A, not increase
      but reduce urinary alpha-CEHC excretion in rats.
AB  - In this study, the CYP3A inducer pregnenolone-16alpha-carbonitrile (PCN) and the
      CYP3A inhibitor ketoconazole (KCZ) were used to investigate whether the
      metabolism of alpha-tocopherol to its metabolite, alpha-carboxyethyl
      hydroxychroman (alpha-CEHC), is CYP3A-dependent in rats. In experiment 1, two
      groups of Wistar rats were fed for 3 wk with either a basal diet (containing 50
      ppm of alpha-tocopherol) or the same diet containing 10-fold more alpha
      tocopherol. In the last 3 days, each group was divided into 2 subgroups which
      were given a single i.p. injection of either PCN at 75 mg/kg/d (P50 & P500
      groups) or DMSO (D50 & D500 groups). The liver TBARS concentration was highest in
      the P50 group. Two-way ANOVA analysis showed that alpha-tocopherol levels in the
      plasma and liver were both significantly decreased by PCN (p < 0.0001), as were
      alpha-CEHC levels in the urine (p = 0.0004). In experiment 2, alpha-tocopherol
      levels in the liver were increased and alpha-CEHC excretion in the urine
      decreased in the Wistar rats fed with KCZ containing diet. In experiment 3,
      Wistar rats administered with dexamethasone (DEX) significantly decreased alpha
      tocopherol levels in the plasma and liver and alpha-CEHC levels in the urine.
      These data showed CYP3A is not a major contributor of the metabolism of alpha
      tocopherol to alpha-CEHC. Nevertheless, vitamin E status was markedly reduced by
      CYP3A inducers due to increased lipid peroxidation and this would increase the
      consumption of alpha-tocopherol in the liver.

PMID- 18806312
TI  - NTPDase and 5'-nucleotidase activities in physiological and disease conditions:
      new perspectives for human health.
AB  - Extracellular nucleotides and nucleosides act as signaling molecules involved in
      a wide spectrum of biological effects. Their levels are controlled by a complex
      cell surface-located group of enzymes called ectonucleotidases. There are four
      major families of ectonucleotidases, nucleoside triphosphate diphosphohydrolases
      (NTPDases/CD39), ectonucleotide pyrophosphatase/phosphodiesterases (E-NPPs),
      alkaline phosphatases and ecto-5'-nucleotidase. In the last few years,
      substantial progress has been made toward the molecular identification of members
      of the ectonucleotidase families and their enzyme structures and functions. In
      this review, there is an emphasis on the involvement of NTPDase and 5'
      nucleotidase activities in disease processes in several tissues and cell types.
      Brief background information is given about the general characteristics of these
      enzymes, followed by a discussion of their roles in thromboregulatory events in
      diabetes, hypertension, hypercholesterolemia and cancer, as well as in
      pathological conditions where platelets are less responsive, such as in chronic
      renal failure. In addition, immunomodulation and cell-cell interactions involving
      these enzymes are considered, as well as ATP and ADP hydrolysis under different
      clinical conditions related with alterations in the immune system, such as acute
      lymphoblastic leukemia (ALL), B-chronic lymphocytic leukemia (B-CLL) and
      infections associated with human immunodeficiency virus (HIV). Finally, changes
      in ATP, ADP and AMP hydrolysis induced by inborn errors of metabolism, seizures
      and epilepsy are discussed in order to highlight the importance of these enzymes
      in the control of neuronal activity in pathological conditions. Despite advances
      made toward understanding the molecular structure of ectonucleotidases, much more
      investigation will be necessary to entirely grasp their role in physiological and
      pathological conditions.

PMID- 18806313
TI  - Attenuation of mitochondrial injury by L-arginine preconditioning of the liver.
AB  - The present study was aimed to evaluate the efficacy of L-arginine on
      mitochondrial function in ischemic and reperfusion (I/R) induced hepatic injury.
      Adult Wistar rat were subjected to 1 h of partial liver ischemia followed by 3
      hour reperfusion. Eighteen wistar rats were divided into three groups viz. sham
      operated control group (I) (n=6), ischemia and reperfusion (I/R) group (II)
      (n=6), L-arginine treated group (100 mg/kg body weight/daily by oral route for 7
      days before induced ischemia reperfusion maneuver) (III) (n=6). Mitochondrial
      injury was assessed in terms of decreased (P<0.05) activities of mitochondrial
      antioxidant enzymes (GSH, SOD, CAT), respiratory marker enzymes (NADH
      dehydrogenase, cytochrome c oxidases) and hepatocytes nitric oxide production.
      Pre-treatment with L-arginine (10 mg/kg/p.o. for 7 days) significantly
      counteracted the alternations of hepatic enzymes and mitochondrial respiratory
      and antioxidant enzymes. In addition, electron microscopy and histopathology
      study showed the restoration of cellular normalcy and accredits the
      cytoprotective role of L-arginine against I/R induced hepatocellular injury. On
      the basis of these findings it may be concluded that L-arginine protects
      mitochondrial function in hepatic ischemic and reperfused liver.

PMID- 18806314
TI  - Suppressive effects of demethylated metabolites of nobiletin on phorbol ester
      induced expression of scavenger receptor genes in THP-1 human monocytic cells.
AB  - Unregulated uptake of oxidized low-density lipoproteins (ox-LDL) via macrophage
      scavenger receptors (SRs) is a key event in atherosclerosis. We previously
      reported that nobiletin (NOB), a citrus polymethoxylated flavone, markedly
      reduced 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced SRs and adhesion
      molecules mRNA expression and blockade of DiI-acLDL uptake in THP-1 human
      monocyte-like cells. In this study, we examined the effects of NOB metabolites,
      3'-hydroxy-5,6,7,8,4'-pentamethoxyflavone (3'-demethyl-NOB), 4'-hydroxy
      5,6,7,8,3'-pentamethoxyflavone (4'-demethyl-NOB) and 3', 4'-dihydroxy-5,6,7,8,
      tetramethoxyflavone (3', 4'-didemethyl-NOB) and NOB analog, tangeretin, on SRs
      and adhesion molecules mRNA expression. 3'-Demethyl-NOB significantly suppressed
      CD36 expression, moreover, 4'-demethyl- and 3', 4'-didemethyl-NOB significantly
      suppressed TPA-induced expression of SR-A and LOX-1. Further, the suppressive
      effects of 4'-demethyl- and 3', 4'-didemethyl-NOB on the expression of CD36 mRNA
      were greater extent than parent NOB. The inhibitory effects of the metabolites
      toward TPA-induced SR mRNA expression are partly associated with the suppression
      of AP-1 and NF-kappaB transcriptional activities. Together, our results suggest
      that metabolites of NOB, such as 4'-demethyl- and 3', 4'-didemethyl-NOB, have
      comparable or higher potentials to attenuate SR expression than NOB.

PMID- 18806315
TI  - Survival rate of preantral follicles derived from vitrified neonate mouse ovarian
      tissue by Cryotop and conventional methods.
AB  - The aim of this study was to investigate the growth and survival rate of
      preantral follicles isolated from vitrified ovarian tissue by Cryotop and
      conventional methods. The ovaries of 14-day-old mice were separated and divided
      into four groups as following: Cryotop group, vitrified by Cryotop; CV
      (Conventional; CV) group, vitrified by conventional straw; toxicity test group
      and control group. After warming the vitrified ovaries, isolated preantral
      follicles from four groups were cultured for 4 days to compare survival rate and
      follicular growth between above-mentioned groups. Survival rate (97.3%) in
      toxicity test group alike the control group (98.7%) were significantly higher
      (P<0.05) than the Cryotop (92.7%) and CV (47.7%) groups. Increase in follicle
      diameters after 4 days in Cryotop and CV groups was significantly lower (P<0.05)
      than the control and toxicity test groups, but growth and survival rate of
      follicles in Cryotop group was significantly higher (P<0.05) than the CV group.
      These results demonstrated that ovarian tissue vitrification by Cryotop highly
      preserves the viability rate of preantral follicles.

PMID- 18806316
TI  - Serum selenium concentration in healthy children living in Tehran.
AB  - INTRODUCTION: Selenium is one of the essential trace elements which is more
      notified in children in recent years. Reliable age-specific reference values for
      selenium in children in Iran are not clear and are important for the
      identification of selenium deficiency and some other researches that is the aim
      of this study. METHODS: Serum samples of 216 healthy children were analyzed by
      using hydride generation and flame atomic absorption spectroscopy to measured
      selenium level. RESULTS: The mean and standard deviation of serum selenium level
      in children 0-16 years old (mean: 39.83 months) was 72.14+/-16.80 microg/l. There
      was significant difference in serum selenium concentration between two sexes
      which was 76.78+/-15.24 microg/l and 69.56+/-17.09 microg/l in girls and boys
      respectively (P value=0.002). There was also a positive correlation between
      higher selenium serum concentration and age in both sexes. CONCLUSION: Essential
      trace element's normal ranges are fundamental data which could use in many
      studies. Serum selenium concentration in healthy Iranian children that found in
      this study is very close to serum concentration of European children. Our
      findings may reveal nutritional culture's similarity.

PMID- 18806317
TI  - Gene expression in arcuate nucleus-median eminence of rats treated with leptin or
      ciliary neurotrophic factor.
AB  - Ciliary neurotrophic factor (CNTF) and leptin are cytokine-like% hormones and act
      on their corresponding receptors in the hypothalamic arcuate nucleus (ARC). The
      present study was designed to assess effects of intracerebroventricular (ICV)
      injection of leptin and CNTF on gene expression in micropunched hypothalamic
      arcuate nucleus-median eminence (ARC-ME) complex samples from rats. Male Sprague
      Dawley rats were implanted with lateral cerebroventricular cannulas for
      administration of control, 10 microg/d leptin or 5 microg/d CNTF for four days.
      Real-time Taqmantrade mark RT-PCR was used to quantitatively compare the mRNA
      levels of selected genes in the ARC-ME complex. Leptin and CNTF increased ARC-ME
      mRNA levels of signal transducer and activator of transcription 3 (STAT3) by 64.5
      and 124.7% (p<0.01), suppressor of cytokine signaling 3 (SOCS3) by 258.9 and
      1063.9% (p<0.01), cocaine and amphetamine regulated transcript (CART) by 102.7
      and 123.1% (p<0.01), and proopiomelanocortin (POMC2) by 374.1 and 264.9%
      (p<0.01), respectively. Leptin increased growth hormone releasing hormone (GHRH)
      by 309.9% (p<0.01), while CNTF increased janus kinase 2 (JAK2) mRNA by 31.7%
      (p<0.01) and decreased gonadotropin releasing hormone 1 (GNRH1) by 59.7%
      (p<0.01), mitogen activated protein kinase 1 (MAPK1) by 19.4% (p<0.05) and
      tyrosine hydroxylase (TH) by 74.5% (p<0.05). Significant reduction in daily food
      intake and body weights by both the treatments was observed. Also, decrease in
      weights of fat pads was concomitant with lowered serum insulin and leptin levels.
      Our findings show that leptin and CNTF engage both convergent and divergent
      pathways involved in feeding, cellular signaling, inflammation, and other related
      regulatory systems.

PMID- 18806318
TI  - Guideline development.
AB  - During the last decade many countries have become increasingly interested in the
      development and use of evidence-based practice guidelines, recognising that
      guidelines are key tools to improve the quality and appropriateness of health
      care. They are considered to be the ideal mediator for bridging the gap between
      the growing stream of research findings and actual clinical practice. Systematic
      reviews of guideline evaluations have shown that clinical practice guidelines can
      be an effective means of both changing the process of healthcare delivery and
      improving outcomes. A review of 59 guideline evaluation studies found that, in
      all but 4, statistically significant improvements occurred in clinical practice
      after implementation. A systematic review of 87 studies on the use of guidelines
      concluded that 81 studies revealed evidence of improved patient outcomes.
      Evidence-based guidelines are becoming an important and indispensable part of
      quality healthcare because of their potentials to improve quality and also reduce
      cost of health-care. Adherence to guidelines and protocols may reduce health-care
      costs up to a 25%. We will present an overview of the history of guideline
      development and give some widely used definitions of guidelines. Guidelines are
      developed in a structured and systematic way, this process will be explained
      later. Also implementation tools necessary to put the guidelines into practice in
      an active way, will be discussed.

PMID- 18806319
TI  - Computer-Interpretable Guideline formalisms.
AB  - Implementing Computer-Interpretable Guidelines (CIGs) in active computer-based
      decision support systems promises to improve the acceptance and application of
      guidelines in daily practice. The model and underlying language are the core
      characteristics of every CIG approach. However, currently no standard model or
      language has been accepted by the CIG community. This aim of this chapter is to
      provide an overview of well-known approaches and to formulate a set of (minimal)
      requirements that can be used in the process of developing new CIG approaches or
      improving existing ones. It presents five CIG approaches (the Arden Syntax, GLIF,
      PROforma, Asbru and EON), followed by a general discussion of the strong points
      of each approach as well as their implications for future research.

PMID- 18806320
TI  - From guidelines to careflows: modelling and supporting complex clinical
      processes.
AB  - Research on computer interpretable clinical guidelines has largely focused on
      individual points of care rather than processes of care. Whether we consider
      simple aids like clinical alerts and reminders or more sophisticated data
      interpretation and decision-making, guideline developers tend to focus on
      specific tasks rather than processes like care plans and pathways which are
      extended in time. In contrast, research on business process modelling has
      demonstrated notations and tools which deal directly with process modelling, but
      has not been concerned with problems like data interpretation and decision
      making. In this chapter we describe these two traditions, and compare some of
      their strengths and weaknesses. We also briefly discuss the distinct theoretical
      frameworks which have grown up around them, notably Petri nets for workflow
      modelling and mathematical logics for guidelines. We conclude that these offer
      complementary views of clinical processes and that a key research challenge is
      find a way of unifying them.

PMID- 18806321
TI  - Formal methods for verification of clinical practice guidelines.
AB  - Formal methods play an important role in the development of software and hardware
      systems. In recent years, there has been a growing interest to apply these
      methods in the area of medical guidelines and protocols. This paper summarises
      these efforts, compares the approaches and discusses the role of formal methods
      in this area.

PMID- 18806322
TI  - The temporal aspects of clinical guidelines.
AB  - Temporal aspects play a major role within clinical guidelines. Temporal issues
      arise when considering both guidelines per se, and the application of guidelines
      to specific patients. As a matter of fact, guidelines per se specify different
      diagnostic and?or therapeutic patterns, and temporal constraints on the intended
      times of execution of the actions they contain are an intrinsic part of
      guidelines themselves. Moreover, guidelines must be executed on the basis of
      patients' data, which are intrinsically temporal data (consider, e.g., the time
      when symptoms hold). Devising suitable representation formalisms to properly
      model such pieces of temporal information is a challenging task, for which
      several solutions have been proposed in the last years. Besides representation
      formalisms, temporal reasoning methodologies are also needed. Temporal
      abstraction is needed in order to infer abstract temporal data (as described in
      guideline action conditions) from "raw" timestamped patient data. Moreover,
      temporal constraint propagationis also needed, both at acquisition and at
      execution time. During acquisition, temporal constraint propagation is used to
      detect whether the temporal constraints in the guideline are consistent. At
      execution time, it is needed in order to check whether the actual time of
      execution of actions has respected the temporal constraints in the guideline, and
      to detect which are the next candidate actions to be executed, on the basis of
      the temporal constraints in the guideline. This chapter sketches some of the most
      important recent results about the above issues.

PMID- 18806323
TI  - Planning: supporting and optimizing clinical guidelines execution.
AB  - A crucial feature of computerized clinical guidelines (CGs) lies in the fact that
      they may be used not only as conventional documents (as if they were just free
      text) describing general procedures that users have to follow. In fact, thanks to
      a description of their actions and control flow in some semiformal representation
      language, CGs can also take advantage of Computer Science methods and Information
      Technology infrastructures and techniques, to become executable documents, in the
      sense that they may support clinical decision making and clinical procedures
      execution. In order to reach this goal, some advanced planning techniques,
      originally developed within the Artificial Intelligence (AI) community, may be
      (at least partially) resorted too, after a proper adaptation to the specific CG
      needs has been carried out.

PMID- 18806324
TI  - Adaptation of clinical practice guidelines.
AB  - A rigorous development process of clinical practice guidelines through a
      systematic appraisal of available evidence is costly and time consuming. One way
      to reduce the costs and time, and avoid unnecessary duplication of effort of
      guideline development is by relying on a local adaptation approach of guidelines
      developed at the (inter)national level by expert groups. In this chapter we
      survey the work on guideline adaptation, which includes methodologies, case
      studies, assessment of effectiveness, and related work on guideline adaptation in
      the Artificial Intelligence community.

PMID- 18806325
TI  - Visualization methods to support guideline-based care management.
AB  - Authoring clinical guidelines as well as observing the execution and the
      maintenance of these is a time-consuming and cumbersome task. Usually, clinical
      guidelines are represented in conceptual models, which are very hard to
      understand by domain experts. Furthermore, to analyze the effectiveness and
      usefulness of clinical guidelines they need to be shown in connection with the
      patients' data. In this overview book chapter we present different methods to
      visualize clinical guidelines, patients' data, and the connection thereof.
      Finally, we illustrate how the different visualization methods support the
      various tasks in plan management.

PMID- 18806326
TI  - Compliance with clinical practice guidelines.
AB  - Compliance with clinical practice guidelines is a challenging topic because it
      depends on a variety of factors, some related to guidelines themselves, some
      related to users, and some to the implementation context. Among the former are
      guideline quality, purpose and implementation modality. Among the user-related
      factors are attitude to behavioural changes, authority interventions to foster
      adherence and eventually the type of users (general practitioners, hospital
      professionals, home caregivers, patients, etc.). Context is also crucial because
      organisational issues, such as lack of resources, can hamper guideline
      implementation and sometimes the original guideline intention is overridden by
      the guideline adaptation to a certain setting. This chapter analyses these
      factors and discusses their implications for the development of computerised
      decision support systems. Moreover, it gives examples of non-compliance detection
      and analysis in a specific real-world computerised guideline implementation,
      facing both methodological and practical issues.

PMID- 18806327
TI  - Compliance checking of cancer-screening Careflows: an approach based on
      Computational Logic.
AB  - Clinical guidelines and Careflow systems have been recently identified as a means
      to improve and standardize health care services. A number of ICT-based management
      solutions have been proposed, focussing on several aspects such as specification,
      process logs verification with respect to specification (compliance), enactment
      and administration of careflows. In this paper we introduce the GPROVE framework,
      based on Computational Logic, and focused on the (formal) specification of
      careflows and on the compliance verification of the process executions w.r.t. the
      specified models. In particular, we show its application to the Cancer Screening
      Guideline used by the sanitary organization of the Emilia Romagna region,
      discussing its formalization in GPROVE and the results of the compliance checking
      applied to logs of the screening process.

PMID- 18806328
TI  - Medical guidelines for the patient: introducing the life assistance protocols.
AB  - This paper introduces our preliminary results in the modeling of Life Assistance
      Protocols, a new vision of medical guidelines and protocols through the lenses of
      p-Health. In this context the patient's role in the process is emphasized, the
      actions to be performed less defined and not only clinical situations considered,
      but also healthier lifestyle promotion processes accounted for, where the
      person's preferences and motivations play a key role. We propose a complete
      framework, balancing on classical clinical guideline models and covering both the
      theoretical and the practical aspects of the problem, describing it from
      conceptualization to the execution environment.

PMID- 18806329
TI  - DeGeL: a clinical-guidelines library and automated guideline-support tools.
AB  - Using machine-interpretable clinical guidelines to support evidence-based
      medicine promotes the quality of medical care. In this chapter, we present the
      Digital Electronic Guidelines Library (DeGeL), a comprehensive framework,
      including a Web-based guideline repository and a suite of tools, to support the
      use of automated guidelines for medical care, research, and quality assessment.
      Recently, we have developed a new version (DeGeL.NET) of the digital library and
      of its different tools. We intend to focus in our exposition on DeGeL's major
      tools, in particular for guideline specification in a Web-based and stand alone
      fashion (Uruz and Gesher), tools for search and retrieval (Vaidurya and
      DeGeLookFor) and for run time application (Spock); and to explain how these tools
      are combined within the typical lifecycle of a clinical guideline.

PMID- 18806330
TI  - A constraint-based approach to medical guidelines and protocols.
AB  - Medical guidelines and protocols are documents aimed at improving the quality of
      medical care by offering support in medical decision making in the form of
      management recommendations based on scientific evidence. Whereas medical
      guidelines are intended for nation-wide use, and thus omit medical management
      details that may differ among hospitals, medical protocols are aimed at local
      use, e.g., within hospitals, and, therefore, include more detailed information.
      Although a medical guideline and an associated protocol concerning the management
      of a particular disorder are related to each other, one question is to what
      extent they are different. Formal methods are applied to shed light on this
      issue. A Dutch medical guideline regarding the treatment of breast cancer, and a
      Dutch protocol based on it, are taken as an example.

PMID- 18806331
TI  - TSNet--a distributed architecture for time series analysis.
AB  - This paper describes an infrastructure (TSNet) which can be used by
      geographically separated research groups to develop algorithms for the
      abstraction of complex time series data. The framework was specifically designed
      for the kinds of abstractions required for the application of clinical guidelines
      within intensive care.

PMID- 18806332
TI  - Clinical guidelines and care pathways: a case study applying PROforma decision
      support technology to the breast cancer care pathway.
AB  - PROforma is a formal language for modeling clinical processes that was developed
      by the Advanced Computation Laboratory of Cancer Research UK in 1996, together
      with associated tools, for creating decision support, care planning, clinical
      workflow management and other applications. The technology has been used to
      develop and evaluate a number of decision support applications in range of
      clinical settings. Clinical trials have been carried out and published for seven
      of these applications, all suggesting major positive benefits on a variety of
      outcome measures. The most recent and ongoing project called CREDO is an
      ambitious attempt to address the challenges in deploying sophisticated decision
      support systems in the intricate and convoluted management of chronic diseases,
      taking breast cancer as an example. In this chapter we describe the
      implementation of evidence based clinical guidelines within a complex care
      pathway for patients with breast symptoms and analyse in detail the results of an
      evaluation study. Some important lessons learned during the process are shared
      and future directions are discussed.

PMID- 18806333
TI  - Lessons learned from adapting a generic narrative diabetic-foot guideline to an
      institutional decision-support system.
AB  - Clinical guidelines usually need to be adapted to fit local practice before they
      can be actually used by clinicians. Reasons for adaptation include variations of
      institution setting such as type of practice and location, availability of
      resources, differences in patient populations, local policies, and practice
      patterns. When a guideline is implemented for clinical decision support and
      integrated with an institution's clinical information system, the data model of
      the local electronic medical record (EMR) and the data actually collected and
      stored in it also influence the guideline's adaptation. The purpose of this work
      is: (1) to characterize a tool-supported process for guideline encoding that
      addresses local adaptation and EMR integration, and (2) to identify the types of
      changes in guideline encoding during the local adaptation process.

PMID- 18806334
TI  - Verification of medical guidelines in KIV.
AB  - We propose to use computerised medical guidelines as models for verification
      tools, so they can be validated with medical properties. To test the
      applicability we provide an implementation of the semantics of the medical
      planning language Asbru and also provide a formalised guideline for the treatment
      of breast cancer. With this case study we conduct experiments testing different
      proof techniques to cope with several challenges which guidelines provide.

PMID- 18806335
TI  - Improving the execution of clinical guidelines and temporal data abstraction high
      frequency domains.
AB  - The execution of clinical guidelines and protocols (CGPs) is a challenging task
      in high-frequency domains such as Intensive Care Units. On the one hand,
      sophisticated temporal data abstraction is required to match the low-level
      information from monitoring devices and electronic patient records with the high
      level concepts in the CGPs. On the other hand, the frequency of the data
      delivered by monitoring devices mandates a highly efficient implementation of the
      reasoning engine which handles both data abstraction and execution of the
      guideline. The language Asbru represents CGPs as a hierarchy of skeletal plans
      and integrates intelligent temporal data abstraction with plan execution to
      bridge the gap between measurements and concepts in CGPs. We present our Asbru
      interpreter, which compiles abstraction rules and plans into a network of
      abstraction modules by the system. This network performs the content of the plans
      triggered by the arriving patient data. Our approach evaluated to be efficient
      enough to handle high-frequency data while coping with complex guidelines and
      temporal data abstraction.

PMID- 18806336
TI  - Applying artificial intelligence to clinical guidelines: the GLARE approach.
AB  - We present GLARE, a domain-independent system for acquiring, representing and
      executing clinical guidelines (GL). GLARE is characterized by the adoption of
      Artificial Intelligence (AI) techniques in the definition and implementation of
      the system. First of all, a high-level and user-friendly knowledge representation
      language has been designed. Second, a user-friendly acquisition tool, which
      provides expert physicians with various forms of help, has been implemented.
      Third, a tool for executing GL on a specific patient has been made available. At
      all the levels above, advanced AI techniques have been exploited, in order to
      enhance flexibility and user-friendliness and to provide decision support.
      Specifically, this chapter focuses on the methods we have developed in order to
      cope with (i) automatic resource-based adaptation of GL, (ii) representation and
      reasoning about temporal constraints in GL, (iii) decision making support, and
      (iv) model-based verification. We stress that, although we have devised such
      techniques within the GLARE project, they are mostly system-independent, so that
      they might be applied to other guideline management systems.

PMID- 18806337
TI  - Japanese encephalitis: surveillance and elimination effort in Japan from 1982 to
      2004.
AB  - Japanese encephalitis (JE) surveillance has been conducted since 1965 as a part
      of the National Epidemiological Surveillance of Vaccine Preventable Diseases in
      Japan. Over 1,000 JE cases were reported annually in the late 1960s. The number
      of JE cases has since markedly decreased, with less than 10 cases reported
      annually from 1992 to 2004. A total of 361 JE cases were reported between 1982
      and 2004. Prognosis was available for 320 cases; 58 (18%) died, 160 (50%)
      recovered with neuropsychiatric sequelae, and 102 (32%) completely recovered.
      Seventy-eight percent of these cases were 40 years old or over with a peak age
      group of 60-69 years old. JE predominantly occurred in unvaccinated populations.
      A high seroconversion rate among sentinel pigs was recorded every year. This
      suggests the presence of JE virus-infected mosquitoes during the summer in most
      areas of Japan, including the northern districts where no JE cases were reported
      from 1982 to 2004. Although JE cases have been reported in single figures since
      1992, the risk of JE virus infection is still present. Thus, high immunization
      rates of JE vaccine should be maintained in Japan.

PMID- 18806338
TI  - Incidence, etiology, and antibiotic resistance patterns of gram-negative
      microorganisms isolated from patients with ventilator-associated pneumonia in a
      medical-surgical intensive care unit of a teaching hospital in istanbul, Turkey
      (2004-2006).
AB  - The identification of microorganisms causing ventilator-associated pneumonia
      (VAP) is important for formulating appropriate therapies. In this study, we
      report the incidence, etiology, and antibiotic resistance patterns of Gram
      negative microorganisms isolated from patients diagnosed with VAP in our medical
      surgical intensive care unit (ICU) during the years 2004-2006. VAP was diagnosed
      by using the clinical criteria of the Centers for Disease Control and Prevention.
      Antibiotic resistance patterns of isolated microorganisms were defined by
      standard methods. The VAP incidence rate was 22.6/1,000 ventilator days. The most
      frequently isolated pathogens were Acinetobacter spp., methicillin-resistant
      Staphylococcus aureus, and Pseudomonas aeruginosa. Ninety percent of
      Acinetobacter spp. isolates were resistant to ceftazidime, 64% to imipenem, and
      80% to ciprofloxacin. Fifty-nine percent of P. aeruginosa isolates were resistant
      to ceftazidime, 32% to imipenem, and 62% to ciprofloxacin. Cefoperazone-sulbactam
      was the most active agent against Acinetobacter spp. In conclusion, the incidence
      of VAP and the prevalence of multidrug-resistant microorganisms are quite high in
      our ICU. Comparison of the resistance rates of isolates demonstrates that certain
      antibiotic agents are more effective than others.

PMID- 18806339
TI  - Molecular diversity of class 1 integrons in human isolates of Aeromonas spp. from
      southern Taiwan.
AB  - This work studies antimicrobial resistance and class 1 integrons of Aeromonas
      spp. in human isolates from southern Taiwan. PCR amplification and DNA sequence
      analyses were performed to characterize the gene cassette regions of the class 1
      integron in 204 isolates of Aeromonas hydrophila, 36 isolates of A. sobria, 23
      isolates of A. veronii, and 4 isolates of A. caviae. By using Southern
      hybridization with an intI1 probe to determine the presence of class 1 integrons
      in the 9 isolates of Aeromonas spp. harboring plasmid DNA, only 2 isolates, one
      A. veronii AV69 harboring 176-kb plasmid DNA, and one A. hydrophila AH207
      harboring 149-kb plasmid DNA were identified. A conjugation experiment was
      carried out with 2 isolates of A. veronii AV69 and A. hydrophila AH207. Only one
      transconjugant of Escherichia coli AH207, containing 149-kb plasmids obtained
      from A. hydrophila AH207, was identified. ERIC-PCR analysis was performed to
      analyze the genetic relatedness in all isolates of Aeromonas spp. that carry
      class 1 integrons. The results of cluster analysis in this experiment revealed
      that none of these isolates were clonal, which may indicate that they were not
      related to the outbreak. Among the 267 isolates tested, class 1 integrons were
      detected in 37 isolates (13.9%) of Aeromonas spp. from humans. No class 2 or
      class 3 integrons were detected in this study. Gene cassette structures were
      identified in 30 (81.0%) of 37 isolates of Aeromonas spp. containing class 1
      integrons. The gene cassette of dfrA12-orfF-aadA2 was the most prevalent in the
      gene cassette array (16.0%), followed by arr3-aacA4 (13.3%) and dfr2d-catB3-aadA1
      (10.0%). Four novel arrays of gene cassettes were also identified, namely, dfr2d
      catB3-aadA1, aadA1-aac(6')-II, aadA4a, and aac(6')-II-blaOXA-21-catB3. This is
      the first report of Aeromonas spp. isolates from humans.

PMID- 18806340
TI  - Incidence of bacterial enteropathogens among hospitalized diarrhea patients from
      Orissa, India.
AB  - Bacteriological analysis of 1,551 stool/rectal swabs from all age groups of
      diarrhea patients of different hospitals of Orissa from January 2004 to December
      2006 was carried out using standard procedures. Among all enteropathogens
      isolated in 886 culture-positive samples, Escherichia coli constituted 75.5%,
      including 13.2% pathogenic E. coli; Vibrio cholerae O1 constituted 17.3%; V.
      cholerae O139, 1%; Shigella spp., 4.5% (Shigella flexneri type 6, 2.9%, S.
      dysenteriae type I, 0.7%, S. sonnei, 0.6%, and S. boydii, 0.3%); Salmonella spp.,
      0.7%; and Aeromonas spp., only 2.0%. The isolation of bacterial enteropathogens
      was highest during July, 2005, followed by September, 2006. The prevalence of
      shigellosis in this region was relatively low. Cholera cases were more frequent
      during the rainy seasons. The dominance of V. cholerae O1 Inaba over Ogawa
      serotypes was observed in 2005, whereas this trend was reversed in 2006. The
      resistance profile of V. cholerae O1 was co-trimoxazole (Co), furazolidone (Fr),
      and nalidixic acid (Na); for Aeromonas spp., it was ampicillin (A), Fr,
      ciprofloxacin (Cf), Na, norfloxacin (Nx), and Co. Pathogenic E. coli strains were
      resistant to A, Fr, Co, streptomycin (S), Cf, Na, Nx, and neomycin (N); Shigella
      spp. were resistant to Fr, Na, Co, and S; and Salmonella spp. were resistant to A
      and Fr. Active surveillance should be continued among diarrhea patients to look
      for different enteropathogens and to define the shifting antibiogram patterns in
      this region.

PMID- 18806341
TI  - Bacillary dysentery and meteorological factors in northeastern China: a
      historical review based on classification and regression trees.
AB  - The relationship between the incidence of bacillary dysentery and meteorological
      factors was investigated. Data on bacillary dysentery incidence in Shenyang from
      1990 to 1996 were obtained from Liaoning Provincial Center for Disease Control
      and Prevention, and meteorological data such as atmospheric pressure, air
      temperature, precipitation, evaporation, wind speed, and the amount of solar
      radiation were obtained from Shenyang Meteorological Bureau. Kendall and Spearman
      correlations were used to analyze the relationship between bacillary dysentery
      and meteorological factors. The incidence of bacillary dysentery was treated as a
      response variable, and meteorological factors were treated as predictable
      variables. Software R 2.3.1 was used to execute the classification and regression
      trees (CART). The model improved the accuracy of the fitting results. The
      residual sum square error of the regression tree model was 53.9, while the
      residual sum square error of the multivariate linear regression model was 107.2.
      Among all the meteorological indexes, relative humidity, minimum temperature, and
      pressure one month prior were statistically influential factors in the
      multivariate regression tree model. CART may be a useful tool for dealing with
      heterogeneous data, as it can serve as a decision support tool and is notable for
      its simplicity and ease.

PMID- 18806342
TI  - The impacts of current antiretroviral therapy regimens on Chinese AIDS patients
      and their implications for HIV-1 drug resistance mutation.
AB  - This study sought to investigate the impacts of the antiretroviral (ARV) therapy
      regimens currently used in Chinese HIV-1-infected individuals. Seven hundred
      eighteen ARV-treated and treatment-naive HIV-1-infected individuals living in
      seven provinces were enrolled in 2005 by a multistage sampling approach according
      to a national cross-sectional survey program on HIV-1 drug resistance. All
      patients were investigated clinically, and CD4+ T cell counts and HIV-1 viral
      loads were measured while genotyping for drug resistance was determined by a home
      brew nested PCR. Viral inhibition in ARV-treated individuals was higher than that
      in ARV treatment-naive individuals. The overall prevalence of drug-resistant
      mutations was 37.8%. Higher frequencies of mutations in ARV-treated and drug
      withdrawal groups were found than in the ARV treatment-naive group (P<0.01). Of
      the four regimens currently used, the D4T/3TC/NVP regimen showed a higher-level
      viral inhibition. No statistical significance was found among the four regimens
      in drug-resistant mutations. The rate of resistance-associated mutations to non
      nucleotide reverse transcriptase inhibitors (NNRTIs) was higher than that to
      nucleotide reverse transcriptase inhibitors (NRTIs) (P<0.01). The most common
      mutations conferring resistance to NNRTIs were K103N, Y181C and G190A,
      representing 56.5, 30.4 and 14.5%, respectively. Furthermore, higher viral
      inhibition and a lower rate of drug-resistant mutations were achieved in the good
      compliance group. This study revealed an efficient viral inhibition achieved with
      the current first-line regimens in China. Most of these regimens could rapidly
      result in emergence of drug-resistant mutations, suggesting that a second-line
      ARV therapy is urgently needed and that the compliance with treatment must be
      emphasized during long-term treatment.

PMID- 18806343
TI  - Assessment of diagnostic enzyme-linked immunosorbent assay kit and serological
      markers in human brucellosis.
AB  - This study was performed to evaluate commercial brucella immunoglobulin G and M
      enzyme-linked immunosorbent assay (IgG and IgM ELISA) kits for the diagnosis of
      human brucellosis and to suggest a candidate prognostic marker for human
      brucellosis. We determined the serum levels of brucella IgG, IgM, C-reactive
      protein (CRP), soluble CD14 (sCD14), and neopterin in patients with brucellosis
      and compared them with those of normal healthy persons, patients with
      tuberculosis, and patients with other diseases. It was found that the sensitivity
      of ELISA to diagnose brucellosis was high when both IgG and IgM ELISA were used
      together. This study showed that serum CRP, sCD14, or neopterin levels were
      significantly high during the course of human brucellosis. The above markers,
      alone or in combination, might have the potential to evaluate treatment outcomes
      in human brucellosis. The markers that can predict the variability of
      agglutination titer was also determined. It was found that the titer value alone
      does not fully represent disease status.

PMID- 18806344
TI  - Assessment of serum anti-Bordetella pertussis antibody titers among medical staff
      members.
AB  - This study comparatively evaluated the titers of the bacterial agglutination (BA)
      antibody for Bordetella pertussis, anti-pertussis toxin (PT) antibody, and anti
      filamentous hemagglutinin (FHA) antibody in the serum of medical staff members.
      The geometric means of the anti-PT and anti-FHA antibody titers were 5.83 and
      17.17 EU/mL, respectively. The positive rates of the BA antibodies against Tohama
      and Yamaguchi strains (> or = 40x), and anti-PT and anti-FHA antibodies (>10
      EU/mL) were 81.3, 72.9, 43.8, and 68.8%, respectively. A high anti-PT antibody
      titer (>94 EU/mL) was found in 1 staff member, but this individual had no recent
      respiratory symptoms. The titers of the BA antibody against the Yamaguchi strain
      were weakly associated with the anti-PT antibody titers, but the BA antibody
      titer was not useful for predicting anti-PT antibody positivity. The
      seroprevalence of anti-pertussis antibody among medical staff was heterogeneous,
      suggesting that this group could be at high risk for pertussis. Judgments made
      using BA antibody or anti-PA antibody results differ, and thus careful evaluation
      of anti-pertussis antibody titers is necessary. Prompt and accurate diagnostic
      tools are crucial for infection control in the hospital setting.

PMID- 18806345
TI  - The roles of the quorum-sensing system in the release of extracellular DNA,
      lipopolysaccharide, and membrane vesicles from Pseudomonas aeruginosa.
AB  - Biofilms play an important role in the establishment of chronic infection caused
      by Pseudomonas aeruginosa. It has been suggested that membrane vesicles (MVs) are
      released into the surrounding medium during normal growth and might supply the
      bacterial extracellular DNA that is required for early biofilm formation, as MVs
      released from the bacterial outer membrane are suspected to be the source of
      extracellular DNA. MVs possess lipopolysaccharide (LPS), extracellular DNA, and
      several hydrolytic enzymes. It is well known that the quorum-sensing (QS) system
      is important in controlling virulence factors in P. aeruginosa and biofilm
      formation. In the current study, we investigated extracellular LPS and DNA in the
      supernatants of culture solutions from PAO1, the wild-type P. aeruginosa, and
      those of QS mutants. As compared to that of las QS mutants, the amount of LPS and
      DNA released was significantly higher in PAO1 and in las QS mutants complemented
      with N-(3-oxododecanoyl) homoserine lactone. Our study indicated that the QS is
      among the regulators involved in the release of extracellular DNA and LPS. It is
      possible that these extracellular components are supplied from MVs. Investigation
      of the mechanism of biofilm formation is of particular interest, as it may be
      useful for designing treatments for severe P. aeruginosa infection.

PMID- 18806346
TI  - A case of Legionella pneumophila pneumonia followed by invasive aspergillosis.
AB  - We report a rare case of Legionella pneumophila pneumonia followed by invasive
      aspergillosis (IA). Legionellosis was ameliorated by the administration of
      ciprofloxacin, erythromycin, and corticosteroid as adjunctive therapy. Although
      intravenous administration of the corticosteroid was effective at reducing severe
      inflammation due to legionellosis, IA occurred at 12 days after admission.
      Combination therapy with micafungin and voriconazole was effective in this case;
      however, it remains necessary to exercise caution when making decisions regarding
      indications for corticosteroid use and observation in the treatment of severe
      pneumonia patients.

PMID- 18806347
TI  - Temporal alterations in concentrations of sera cytokines/chemokines in sepsis due
      to group B streptococcus infection in a neonate.
AB  - Group B streptococcus (GBS) is the most common pathogen in neonates and may
      induce the overproduction of cytokines. To further clarify temporal alterations
      in the levels of various cytokines/chemokines, we measured the concentrations of
      16 types of these immunological responders in the serum of a neonate presenting
      with GBS infection. At birth, the concentrations of different
      cytokines/chemokines increased and that of granulocyte colony-stimulating factor
      remained high. Thus, these cytokines/chemokines might be associated with the
      pathophysiology of GBS infection.

PMID- 18806348
TI  - Hemorrhagic fever with renal syndrome in Montenegro.
AB  - The objective of the study was to analyze the epidemiological features of
      hemorrhagic fever with renal syndrome (HFRS) in Montenegro. The study included
      169 cases of HFRS diagnosed in the period between 1995 and 2005 according to the
      clinical symptoms and serological confirmation. For the analysis of the
      demographic characteristics of the cases, as well as of the chronological and
      topographical features of the disease, a descriptive epidemiological method was
      employed. The average incidence rate in the observed period was 2.6 per 100,000.
      In the observed period, 8 people died; the average case fatality rate was 4.8%
      (range: 0.1-15%). Among the diseased persons, 116 were males and 53 were females;
      most of the cases were adults. The greatest number of HFRS cases occurred during
      the summer months. The highest incidence rates were registered in the
      northeastern, rural part of the country. The most frequent type of hantaviruses
      in Montenegro were Dobrava-Belgrade and Hantaan, carried by rodent species, i.e.,
      the yellow-neck mouse and the striped-field mouse. It is likely that HFRS in
      Montenegro will become more common in the near future, unless public health
      control measures are taken.

PMID- 18806349
TI  - Risk factors for SARS infection within hospitals in Hanoi, Vietnam.
AB  - We investigated a nosocomial infection of severe acute respiratory syndrome
      (SARS) in Vietnam in 2003 and attempted to identify risk factors for SARS
      infection. Of the 146 subjects who came into contact with SARS patients at
      Hospital A, 43 (29.5%) developed SARS, and an additional 16 (11%) were
      asymptomatic but SARS-coronavirus (CoV) seropositive. The asymptomatic infection
      rate accounted for 15.5% of the total number of infected patients at Hospital A,
      which was higher than that of 6.5% observed at Hospital B, to where all patients
      from Hospital A were eventually transported (P<0.05). At Hospital A, the risk for
      developing SARS was 12.6 times higher in individuals not using a mask than in
      those using a mask. The SARS epidemic in Vietnam resulted in numerous secondary
      infections due to its unknown etiology and delayed recognition at the beginning
      of the epidemic. The consistent and proper use of a mask was shown to be crucial
      for constant protection against infection with SARS.

PMID- 18806350
TI  - Relationship of frequency of CD4+CD25+Foxp3+ regulatory T cells with disease
      progression in antiretroviral-naive HIV-1 infected Chinese.
AB  - Forty-five antiretroviral-naive HIV-1 infected patients and 14 healthy controls
      in North China were enrolled in this study. The frequency of CD4+CD25+Foxp3+
      regulatory T cells (Tregs) and levels of expression of CD95, HLA-DR and CD38 in T
      cells were detected by flow cytometry. We found that the frequency of Tregs was
      higher in AIDS patients than in asymptomatic HIV-1 infected patients (P=0.004).
      The frequency of Tregs was significantly correlated with absolute CD4 count,
      viral load, CD4+CD95+ T cells and CD8+CD95+ T cells (P<0.05). The relationship
      between the frequency of Tregs and immune activation was not found in HIV
      infected patients. We concluded that the frequency of Tregs in HIV-infected
      Chinese patients was significantly correlated with disease progression.

PMID- 18806351
TI  - Genetic characterization of Staphylococcus aureus isolates carrying Panton
      Valentine leukocidin genes in Bangladesh.
AB  - To assess the spread and genetic characteristics of Panton-Valentine leukocidin
      (PVL) gene-carrying Staphylococcus aureus in Bangladesh, we investigated 59
      strains (49 isolates from clinical specimens and 10 isolates colonized in the
      nasal cavities of medical staff), including 26 methicillin-resistant S. aureus
      (MRSA) strains. The PVL gene was detected only in methicillin-susceptible S.
      aureus (MSSA) strains (7 clinical strains and 2 colonizing strains). PVL gene
      positive MSSA strains were found to belong to coagulase serotypes III or VI and
      were classified into sequence types ST88 (CC88), ST772, and ST573 (CC1) by
      multilocus sequence typing, and agr types 2 or 3. These types were different from
      those determined for MRSA (coagulase serotypes I and IV, ST240 and ST361, and agr
      type 1). PVL gene-positive MSSA possessed a larger number of virulence factor
      genes than MRSA, although they were susceptible to more antimicrobials. These
      findings suggest that the PVL gene is distributed to limited populations of S.
      aureus clones with specific genetic traits that are distinct from MRSA in
      Bangladesh, but genetically close to CA-MRSA clones in the CC1 lineage reported
      in the United States and European countries.

PMID- 18806352
TI  - Do serological tests provide adequate rapid diagnosis of Mycoplasma pneumoniae
      infection?
AB  - This study was designed to evaluate the serologic response to Mycoplasma
      pneumoniae infection. A total of 589 children < or =18 years (190 in the year
      2004; 399 in 2005) and 2,073 adults > or = 18 years of age (980 in the year 2004;
      1,093 in 2005) with respiratory symptoms underwent serological testing for M.
      pneumoniae infection. The tests included passive particle agglutination (PA) and
      enzyme-linked immunosorbent assay (ELISA). The seroprevalence rates of M.
      pneumoniae infection in the years 2004 and 2005 were 6.9 and 10.1%, respectively.
      The seropositivity rate was significantly higher in children (29.6% in 2005;
      23.7% in 2004) than in adults (2.9% in 2005; 3.7% in 2004) (odds ratio, 8.138 in
      2004; 13.923 in 2005; 95% confidence interval, 5.077-13.045 in 2004; 9.220-21.026
      in 2005). Paired sera for the PA test were obtained from 32 of 399 children, and
      22 of them demonstrated at least fourfold rises in antibody titer. ELISA had a
      sensitivity of 77.3% and a specificity of 40.0%; PA had a sensitivity of 9.5% and
      a specificity of 80%. The ELISA test was superior to the PA test in diagnosing
      acute M. pneumoniae infection in children. Both tests were significantly more
      sensitive when they were performed 1 week after the onset of infection.

PMID- 18806353
TI  - Deaths of early-onset, invasive sepsis in full-term infants in Miyazaki: nine
      cases from a regional population-based analysis from 1998-2006.
AB  - In a population-based study we investigated the early-onset, invasive sepsis
      caused by group B streptococcus (GBS) and non-GBS in the era of intrapartum
      antimicrobial prophylaxis. From 1998 to 2006, we had 387 perinatal deaths in
      98,495 deliveries, and 9 full-term infants met the criteria of early-onset,
      invasive sepsis, in which microorganisms were proven from blood sampling. Of
      these cases, 4 involved GBS, 2 ampicillin-resistant Escherichia coli, 2
      methicillin-resistant Staphylococcus aureus, and 1 was unidentified. All 4 cases
      of GBS related death underwent improper procedures contrary to the prophylaxis
      recommendation. Eighty percent of non-GBS related deaths had septicemia of
      antibiotic-resistant pathogens. We found in our population-based study that early
      onset, fatal sepsis in full-term infants is associated with insufficient
      adherence to the prophylaxis strategy for GBS and with the emergence of
      antimicrobial resistant non-GBS bacteria.

PMID- 18806354
TI  - Analysis of gene expression in mouse alveolar macrophages stimulated with quorum
      sensing mutants of Vibrio vulnificus.
AB  - Bacterial pathogens manipulate host cells to promote pathogen survival and
      dissemination. In this study, microarray technology was used to identify the
      genes that are affected by the Vibrio vulnificus quorum-sensing genes, luxS and
      smcR. By comparing the expression profiles of mouse macrophage cell lines
      stimulated with either the parent strains or a luxS smcR mutant, differentially
      expressed genes were identified. The genes included those that affect host cell
      death, stress, signaling transduction, inflammation, and immune response.
      Macrophages stimulated with the luxS smcR mutant differentially expressed genes
      associated with removal of toxins, the complement pathway, regulation of cytokine
      expression, and antigen presentation, indicating that macrophages stimulated with
      the luxS smcR mutant induced an appropriate inflammation reaction and immune
      response for removal of bacteria. In summary, quorum-sensing in V. vulnificus
      could contribute to bacterial survival and increased pathogenesis by inducing a
      changed expression profile in macrophages.

PMID- 18806355
TI  - An application of duplex PCR for detection of Leptospira spp. and Orientia
      tsutsugamushi from wild rodents.
AB  - Duplex PCR is useful for detecting two different agents from the same specimen.
      Kidney specimens are the most suitable for detection of Leptospira spp. For
      Orientia tsutsugamushi, blood clots, spleen, and liver specimens are considered
      the most suitable. For this study, kidney tissues were the only specimens
      obtainable for the PCR. Blood clots, spleen, and liver specimens were not
      available. However, by using the PCR for scrub typhus, O. tsutsugamushi was
      detected in the kidney of one rodent. This result shows that kidney specimens can
      be used to detect O. tsutsugamushi using PCR. Further studies will be necessary
      in order to be able to compare the detection ratio of O. tsutsugamushi using
      kidney specimens and blood clots, spleen, and liver specimens.

PMID- 18806356
TI  - Vero cells infected with vaccinia viruses expressing Japanese encephalitis virus
      envelope protein induce polykaryocyte formation under neutral conditions.
AB  - Flavivirus membranes fuse with cellular membranes by low pH-induced mechanisms.
      Although Japanese encephalitis virus (JEV) has similar mechanisms, fusion induced
      under neutral conditions has been observed. We report herein polykaryocyte
      formation using Vero cells infected with recombinant vaccinia viruses, vP829
      expressing JEV premembrane (prM) and envelope (E), or vP555 expressing prM, E,
      and the nonstructural proteins NS1 and NS2A. Polykaryocytes were detected under
      pH 7.0 as early as 9 h after infection. Higher fusion indices were shown with
      vP555 than vP829. A monoclonal antibody to E suppressed vP829/vP555-induced
      polykaryocyte formation. Polykaryocytes were also formed under alkaline
      conditions (pH 8.0).

PMID- 18806357
TI  - Infected subdural hematoma in an infant.
AB  - We report the case of a 1-year-old boy with an infected subdural hematoma due to
      Streptococcus pneumoniae identified by latex agglutination test and polymerase
      chain reaction amplification of a bacteria-specific gene. The present case
      demonstrated the need to include infected subdural hematoma in the differential
      diagnosis of suspected subdural empyema, and suggested the usefulness of
      combining these methods to identify a causative organism.

PMID- 18806358
TI  - Assessment of nosocomial transmission of tuberculosis in a psychiatric hospital
      using a whole blood interferon-gamma assay.
AB  - We conducted a contact investigation in a psychiatric hospital to evaluate the
      nosocomial transmission of tuberculosis (TB). Contacts included hospital
      healthcare workers (HCWs) and inpatients who had been exposed to an index case of
      pulmonary TB. Contacts were evaluated for Mycobacterium tuberculosis infection
      with standard screening methods as well as the QuantiFERONR-TB Gold (QFT-G) test.
      A tuberculin skin test (TST) was administered to 3 individuals who were under 30
      years old, and all tests were negative. Chest X-ray examination was performed for
      all 46 contacts (9 HCWs and 37 patients). Five had abnormal chest X-ray results
      that were not compatible with TB, and 41 had normal chest X-rays. As regards the
      QFT-G test, 23 of the 46 (50%) contacts, 1 HCW (an 81year-old male) and 22
      patients, were positive. The results suggest that there was significant
      nosocomial transmission of TB infection among inpatients in this psychiatric
      hospital. Moreover, these findings indicate that the use of chest X-ray and TST,
      i.e., conventional methods of detection will leave TB infection undetected in
      many individuals. Thus, introduction of screening for TB infection using the QFT
      G test in long-term care facilities such as psychiatric hospitals may enable the
      detection and treatment of individuals with latent TB in whom the infection would
      otherwise be missed by other conventional screening methods.

PMID- 18806359
TI  - Multiple outbreaks of gastroenteritis due to a single strain of genotype GII/4
      norovirus in Kobe, Japan, 2006: risk factors for norovirus spread in health care
      settings.
AB  - A large number of gastroenteritis outbreaks due to a norovirus GII/4 strain and
      its variants occurred during November and December 2006 in Kobe, Japan. Of the
      118 outbreaks, 6 were foodborne and 112 were caused by person-to-person
      transmission in healthcare settings such as nursing homes and hospitals. The
      distribution of norovirus outbreaks in healthcare settings was skewed,
      particularly in the south coastal area. Moreover, several outbreaks occurred
      within 1 km(2) in various areas. Outbreaks in neighboring settings, especially
      within 1 km, and travel from the sources of outbreaks were risk factors for the
      spread of the norovirus. The use of ineffective disinfectants such as alcohol and
      benzalkonium chloride might also have helped to spread the infection.

PMID- 18806360
TI  - Food poisoning outbreak caused by norovirus GII/4 in school lunch, Tochigi
      prefecture, Japan.

PMID- 18806361
TI  - Estimation of focus reduction neutralization test for measurement of neutralizing
      antibody titer against Japanese encephalitis virus.

PMID- 18806362
TI  - An outbreak of group A rotavirus G1P[8] in an elementary school, Nara prefecture.

PMID- 18806363
TI  - The effects of massage to the hamstring muscle group on range of motion.
AB  - This study was designed to measure the effect on range of motion of a single
      massage treatment to the hamstring muscle group. Thirty-four normal female
      subjects between 18 and 35 years of age were given a 9- 12 minute massage
      treatment to the posterior aspect of one randomly assigned lower extremity.
      Passive range of motion of both lower extremities was measured by taking the
      perpendicular distance from the lateral malleolus to the table surface in a
      straight leg raise and by conventional goniometry for hip flexion and knee
      extension. Measurements were taken pre-, and post-, and 7-days postmassage
      treatment. Immediate postmassage increases in range of motion were noted in the
      test group (massaged) legs with significance at the 0.05 level. The possible uSe
      of this treatment in athletics and pathological conditions are discussed. J
      Orthop Sports Phys Ther 1984;6(3):168-172.

PMID- 18806364
TI  - Effects of Knowledge of Results on Reciprocal, lsokinefk Strength and Fatigue.
AB  - The purpose of this study was to determine the effects of knowledge of results,
      i.e., visual feedback from watching the torque curve on the Cybex II recorder, on
      knee extensor and flexor strength (peak torque in ft-lb), and fatigue (strength
      decrement) during reciprocal, isokinetic testing at speeds of 15O/sec (slow) and
      300 degrees /sec (fast). Knowledge of results induced higher strength and fatigue
      values in both muscle groups during slow, but not fast, speed tests. The greater
      amounts of fatigue resulted from elevated initial strength levels at the
      beginning of the slow speed fatigue tests. The superior quality of the slow speed
      knowledge of results and longer times to utilize the visual feedback may explain
      the enhanced strength values. The effect of knowledge of results on strength
      levels decreased during the course of the slow speed fatigue tests. Results are
      discussed in terms of information processing and motivation theory. J Orthop
      Sports Phys Ther 1984;6(3):190-197.

PMID- 18806365
TI  - Microcomputers in sports medicine.

PMID- 18806366
TI  - Speed-Specific lsokinetic Training.
AB  - The authors studied the effects of high speed (240 degrees /sec) and low speed
      (60 degrees /sec) isokinetic exercise. Twenty-four subjects were randomly
      selected into one high speed and one low speed treatment group; treatments
      consisted of one set of 15 repetitions, 3 times a week for 6 weeks. Pre- and post
      testing with a Cybex II isokinetic dynamometer was performed to determine if
      significant strength gains were elicited at 30, 60, 180, 240, or 300 degrees
      /sec. Both low and high speed groups produced significant strength gains (0.0 1
      significance level) at their treatment speed and at one testing speed higher.
      However, this study indicates that the range of this carry over is not sufficient
      enough to replace speed-specific training. J Orthop Sports Phys Ther
      1984;6(3):181-183.

PMID- 18806367
TI  - The effect of a forearm strap on wrist - extensor strength*.
AB  - Thirty subjects with no pathology of the right elbow were tested using an
      isokinetic dynamometer to measure wrist extensor strength. Subjects were tested
      under control and experimental conditions with and without a forearm strap. Tests
      were conducted at 30 and 120 degrees /sec. Results were plotted on separate
      graphs using a sequential trials method. No difference in strength was noted at
      the slower speed. A statistically significant increase in strength with the strap
      was found at 120 degrees /sec. It was concluded that, in these subjects, the
      forearm strap made no difference in strength at the slower speed, but
      significantly increased strength at the faster speed. Facilitation due to sensory
      stimulation of the skin and pressure on the muscle belly was offered as an
      explanation. Further research is needed in this area. J Orthop Sports Phys Ther
      1984;6(3):184-189.

PMID- 18806368
TI  - Nutrition and the growing athlete.
AB  - As a group, adolescents demonstrate notoriously poor dietary habits. Sports and
      exercise participation actually encourages young people to attend to nutritional
      concerns. Nutritional factors play a major role in determining the adolescent's
      potential to reach full growth and the maintenance of good health. In addition to
      the effect on growth, food intake (quantity, quality, and pattern of) is a
      critical determinant of athletic performance. A review and synthesis of the
      recent literature concerning characteristics of adolescent athletes and the
      nutritional requirements of growth and performance are provided. Common
      nutritional deficiencies of the young athlete and dietary inadequacies resulting
      in disturbances of growth are identified. Maximal athletic performance and the
      promotion of the present and future good health of young people challenges health
      and fitness professionals to provide adolescents with accurate nutritional
      information and caution against widespread nutritional frauds. J Orthop Sports
      Phys 1984;6(3):173-177.

PMID- 18806369
TI  - Case Study: Isolated Anterior lnterosseous Nerve Paralysis: The - Kiloh-Nevin
      Syndrome.
AB  - A new case of isolated paralysis of the anterior interosseous nerve of a 24-year
      old man is described. It is thought that this was caused by a fall on the left
      arm. This paralysis has a typical clinical picture with a characteristic
      disturbance of the pinch grip. The patient recovered spontaneously. A review of
      the findings previously reported in the literature is presented. J Orthop Sports
      Phy Ther 1984;6(3):178-180.

PMID- 18806370
TI  - Leg length differences and correlation with total leg strength.
AB  - The evaluation of leg length differences is a significant point in the
      examination of a patient. Many problems can result from or underlie a leg length
      discrepancy. These problems occur in both the average population and may be even
      more pronounced in a more athletic group. One problem which is hypothesized is
      that the leg strength of a person with leg length difference is unequal
      bilaterally. This paper will discuss the examination, types of leg length
      differences, the resulting problems of a leg length difference, some basic
      treatments, and then report the results of a study performed to compare leg
      length differences with total leg strength as measured isokinetically.J Orthop
      Sports Phys Ther 1984;6(2):123-129.

PMID- 18806371
TI  - The effect of heat and stretching on the range of hip motion*.
AB  - Flexion, abduction, and external rotation of the hip joint were recorded in 30
      volunteers randomized into three groups of 10. The measurements were taken
      before, immediately after, and 30 minutes after treatment of heat, stretching and
      a combination of heat plus stretching. Heat only did not improve the range of
      motion of the hip joint. Stretching increased flexion and external rotation, and
      heat plus stretching in combination gave the greatest increase in flexion motion,
      and also significantly increased abduction. External rotation after stretching
      treatment, and flexion and abduction after heat plus stretching treatment were
      still significantly increased after 30 minutes.J Orthop Sports Phys Ther
      1984;6(2):110-115.

PMID- 18806372
TI  - Bed transfer for unilateral sacroiliac pain.
AB  - A nontraditional transfer technique is found to be pain-free for a patient with
      unilateral sacroliac joint pain. This method emphasizes constant contact of both
      buttocks to the bed during the entire transfer process.J Orthop Sports Phys Ther
      1984;6(2):140-141.

PMID- 18806373
TI  - The effects of static stretching exercises and stationary cycling on range of
      motion at the hip joint*.
AB  - The objective of this study was to compare the effects of static stretching
      exercises and stationary cycling on hip range of motion measures immediately
      following exercise and after a 15-min period of rest or continued activity. The
      results showed that both exercises performed for equal time periods resulted in
      hip range of motion increases with no significant difference (p < 0.05) between
      the immediate effects of the two exercises. Fifteen minutes of cycling or
      inactivity did not result in significant differences (p < 0.05) from the initial
      gains resulting from the stretching, but did result in significant increases in
      hip flexion for the group that continued cycling. Based on the results of this
      study, static stretching and cycling were equally effective for increasing range
      of motion and retaining the increase for a 15-min period in a controlled
      environment, independent of activity.J Orthop Sports Phys Ther 1984;6(2):104-109.

PMID- 18806374
TI  - Knee brace influences on the tibial rotation and torque patterns of the surgical
      limb.
AB  - Tibial rotation and torque were evaluated using a specifically designed device to
      assess the effects of two different knee braces on the performance of the
      surgically repaired knee. Comparisons were also made with the healthy
      contralateral limb. Six subjects, aged 21 to 28, participated in the study.
      Subjects were tested while seated in an adjustable chair which allowed the torso,
      pelvis, thigh, and femoral condyles to be stabilized utilizing a series of straps
      and brackets. The foot was immobilized by a special boot which was connected to
      the input shaft of a Cybex isokinetic dynamometer. To begin, the foot was
      positioned perpendicular to the frontal plane and the knee position maintained at
      90'' of flexion. Subjects were then asked to maximally externally or internally
      rotate the tibia on the femur during two brace conditions: the surgical limb
      condition and the healthy limb condition. The results indicated that there were
      differences across all conditions of tibia1 range of motion and torque with
      external direction values being significantly greater (P < 0.05). Comparison
      between conditions yielded no significant differences; however, a consistent
      trend characteristic of a knee brace reduction in internal rotation and torque
      parameters were present. J Orthop Sports Phys Ther 1984;6(2):116-122.

PMID- 18806375
TI  - A Preliminary Report on the Use of the McKenzie Protocol versus Williams Protocol
      in the Treatment of Low Back Pain.
AB  - The purpose of this study was to determine whether the Williams or McKenzie
      protocol of treatment was more effective in both decreasing pain and hastening
      the return of pain-free range of lumbar spine movement. Twenty-two subjects
      underwent an initial evaluation which involved six measurements: subjective pain,
      comfortable sitting time, forward flexion, right and left lateral flexion, and
      straight leg raise. Subjects required to perform Williams' protocol were assigned
      accordingly, while those referred as "evaluate and treat" were placed in the
      McKenzie group. Following the completion of treatment, a second evaluation was
      performed taking the same six measurements. A comparison of the improvement
      scores of the two groups indicated that those receiving the McKenzie protocol
      improved to a significantly (P < 0.001) greater extent than did the subjects in
      the Williams group, and that these changes came about in a significantly (P <
      0.01) shorter period of time.J Orthop Sports Phys Ther 1984;6(2):130-139.

PMID- 18806376
TI  - Deep transverse frictions in ligament healing*.
AB  - The purpose of this study was to examine the effect of deep transverse frictions
      on the healing of a minor sprain of the knee medial collateral ligament, in
      rabbits, using histological observations. Right knees of 18 animals were manually
      sprained; left knees served as controls. Deep transverse frictions were given
      five times to six animals; ten times to six animals. It was not possible on
      stained tissue sections to distinguish (P > 0.05) either between sprained or
      unsprained ligaments, or between treated and untreated sprained ligaments. The
      hypothesis that deep transverse frictions promote repair of sprained ligaments is
      not supported by the results of this study.J Orthop Sports Phys 1984;6(2):89-94.

PMID- 18806377
TI  - EMG Biofeedback as Treatment for Patellofemoral Pain Syndrome*.
AB  - Patellofemoral pain syndrome may be classified as a dysfunction of the patella's
      ability to track in the femoral groove. This study identifies an effective
      treatment approach for patellofemoral pain syndrome. The approach integrates the
      concept of improved patellar tracking through selective enhancement of the vastus
      medialis oblique muscle with conventional exercise regimens for patellofemoral
      pain syndrome. Six patellofemoral pain syndrome patients were enrolled in a three
      phase electromyographic biofeedback and exercise program: 1) biofeedback
      orientation and instruction in isometric quadriceps contractions, straight leg
      raises, and a home program; 2) biofeedback training for vastus medialis oblique
      enhancement with isometric quadriceps contractions, straight leg raises, terminal
      knee extensions, and progressive resistive exercises; and 3) incorporation of
      increased vastus medialis oblique activity in functional patterns of movement.
      All six patients learned to alter their vastus medialis oblique activity through
      the use of this treatment approach. The alteration of vastus medialis oblique
      activity resulted in an apparent change in the patellofemoral forces and a
      concomitant decrease in the patients' complaints of pain. These patients were
      able to return to pain-free functional activities in only six to nine treatment
      sessions within a 4- to 6-week period. The use of electromyographic biofeedback
      coupled with a graded exercise program is an efficient and effective treatment
      approach for patellofemoral pain syndrome patients.J Orthop Sports Phys Ther
      1984;6(2):95-103.

PMID- 18806378
TI  - Exercise and uric Acid: implication in cardiovascular disease.
AB  - The association of elevated serum uric acid (SUA) concentration (hyperuricemia)
      with gout has been known for many years, but more recently hyperuricemia has been
      observed to be associated with many of the known major risk factors for coronary
      heart disease (hypertension, stress, hypercholesterolemia) with much greater
      frequency than in the general population. Several epidemiological studies have
      indicated a beneficial relationship between physical activity, risk factor
      modification, and susceptibility to coronary heart disease. Physical activity has
      been shown to modify not only the major identified risk factors but SUA levels as
      well. Whereas acute exercise lasting between one-half and three hours elevates
      SUA in proportion to intensity of exercise, chronic exercise lowers SUA levels.
      Mechanisms for these changes are discussed as well as implications in relation to
      coronary disease.J Orthop Sports Phys Ther 1984;6(1):34-39.

PMID- 18806379
TI  - Stress management for chronic pain patients.

PMID- 18806380
TI  - lsokinetic Evaluation of Tibial Rotation: Assessment of a Stabilization
      Technique*.
AB  - The purpose of this study was to present a wide range of normative data on
      maximum active tibial rotation utilizing isokinetic resistance and a relatively
      new stabilization technique. Both legs of 25 healthy adult male subjects were
      tested at 30, 60, 120, and 180 degrees per second of angular velocity. Data were
      collected on total range of motion, component internal/external range of motion
      (via two different methods), joint position at peak torque production, peak
      torque production, and torque production as a percentage of body weight. The
      effect of weight and leg length on peak torque production and total range of
      motion was also determined. In light of recent studies which have shown the need
      for specific rotational rehabilitation for rotatory knee instabilities, this
      study serves to present normative data for practical use in either the clinical
      or research setting. J Orthop Sports Phys Ther 1984;6(1):46-51.

PMID- 18806381
TI  - Medial tarsal tunnel syndrome: a review.
AB  - The medial tarsal tunnel syndrome is a compression neuropathy involving the
      tibial nerve or its branches as they pass through the tarsal tunnel under the
      flexor retinaculum. Medial tarsal tunnel syndrome is not recognized as readily as
      its counterpart in the wrist. This syndrome can lead to a painful burning
      sensation in the medial border of the foot and into the great toe. In its fullest
      extent medial tarsal tunnel syndrome can involve sensory changes in the heel and
      the lateral part of the sole of the foot as well as the remaining toes. In
      addition, it may lead to weakness of the intrinsic muscles of the foot. This
      syndrome often goes unrecognized or misdiagnosed particularly in the athlete.
      While medial tarsal tunnel syndrome may respond initially to nonoperative
      techniques of ultrasound and modification of footwear, as it progresses surgical
      release of the nerve in the tunnel will be required for optimal results. This
      paper reviews the anatomy, etiology, pathology, clinical presentation, and
      treatment of the medial tarsal tunnel syndrome. In order to bring more attention
      to this condition, our clinical experience is presented.J Orthop Sports Phys Ther
      1984;6(1):39-45.

PMID- 18806382
TI  - Chronic pain: the benefits of being sick.

PMID- 18806383
TI  - Effects of Stabilizing the Nontested Lower Extremity during lsokinetic Evaluation
      of the Quadriceps and Hamstrings*.
AB  - The purpose of this investigation was to determine if stabilization of the
      nontested lower extremity influences the peak torque generated by the knee
      musculature of the opposite extremity during isokinetic testing. The subjects
      included 15 males and 15 females, between 18 to 30 years of age, who had no
      history of right knee pain or pathology. A Cybex I isokinetic dynamometer was
      used to measure the torques generated by the quadriceps and hamstring muscles of
      the right lower extremity during flexion and extension. Each subject performed
      two trials of extension and flexion of the right knee; each trial consisted of
      one set of three contractions at 60 degrees /sec and one set at 180 degrees /sec.
      One trial was performed with the left lower extremity stabilized and the second
      trial was performed without stabilization. The results demonstrate that the peak
      torques generated by the quadriceps and hamstrings of the tested extremity are
      not significantly influenced by stabilization of the opposite lower extremity at
      the speeds tested.J Orthop Sports Phys Ther 1984;6(1):18-20.

PMID- 18806384
TI  - A field test for the assessment of abdominal muscular endurance in professional
      ice hockey players.
AB  - The purpose of this study was to develop a test protocol and produce normative
      data for measuring abdominal muscular endurance in professional ice hockey
      players. The protocol was developed using elite speed skaters and professional
      ice hockey players. The test involves the measurement of total number of curl-ups
      that can be completed at a prescribed rate of 25 repetitions per minute. The test
      protocol maximizes the isolation of the abdominal muscle group and the control of
      the movement. Normative data is presented from tests on 11 7 professional hockey
      players. This protocol provides discriminatory power and has high face validity
      in its application.J Orthop Sports Phys Ther 1984;6(1):30-33.

PMID- 18806385
TI  - Problems faced by the physical therapist in the treatment of chronic pain.

PMID- 18806386
TI  - Pre- and postoperative functional changes in total knee patients.
AB  - Objective laboratory measurements were obtained preoperatively and up to 24
      months postoperatively for 102 patients (140 knees). This longitudinal study was
      an effort to determine changes in functional status as a result of surgery and
      rehabilitation. In the main, the function improved in arthritic patients who
      received a geometric knee implant and subsequent physical therapy in a manner
      described in this study. Function improved in terms of joint motion, muscle
      strength, standing posture, and gait in both rheumatoid and osteoarthritic
      groups. Some functional abnormalities which seemed to persist were deficits in
      knee extension motion and knee extensor strength, and that the subjects stand
      with the knee in a flexed position. Time asymmetries of foot placement were
      present during gait, patient's stance phase time and body accelerations were
      excessive, and body accelerations were arrhythmic in the forward-backward
      directions.J Orthop Sports Phys Ther 1984;6(1):25-29.

PMID- 18806387
TI  - lsokinetic Torque Levels for Adult Females: Effects of Age and Body Size.
AB  - The effects of age and body size on isokinetic torque levels for adult females
      were statistically analyzed. Results indicate that age and to a lesser extent
      weight and height can account for torque differences in adult women.
      Additionally, this relationship exists regardless of speed of movement (i. e., 60
      degrees /sec and 240 degrees /sec).J Orthop Sports Phys Ther 1984;6(1):21-24.

PMID- 18806388
TI  - Pain complaint: comparison of electrical stimulation with conventional isometric
      exercise.
AB  - The purpose of this retrospective study was to assess the pain experiences of 17
      healthy subjects who trained with isometric exercise, electrical stimulation, and
      the combination of isometric exercise and electrical stimulation. The McGill Pain
      Questionnaire was administered during posttest sessions upon termination of 5
      weeks of training. Results indicated that subjects who received the electrical
      stimulation mode of training experienced similar torque gains but less muscle
      soreness than those who used conventional isometric exercise. Most subjects of
      the exercise and electrical stimulation groups experienced pain at the medial
      aspect of their knee, The pain was predominantly expressed as a sensory rather
      than an effective or an evaluative quality. Of all the trained subjects, those
      who received electrical stimulation described the greatest amount of transient
      discomfort. Electrical stimulation does not appear to increase the risk of
      discomfort more than volitional resistive exercise for achieving similar force
      developing capacity of muscle in healthy subjects.J Orthop Sports Phys Ther
      1984;5(6):318-323.

PMID- 18806389
TI  - Analgesic and psychoactive drugs in the chronic pain patient.
AB  - In contrast to the management of pain in patients with malignant disease, where
      manipulation of analgesic and psychoactive drugs may be necessary and effective,
      the elimination of drug use is a primary goal in programs for patients with
      chronic pain of benign rig in.; Drug use is often a significant component of pain
      behavior and, therefore, it is important to alter the use of drugs in freeing the
      patient of the chronic pain syndrome. Elimination of the unwanted side effects
      and medical complications of drug use may contribute significantly to the
      patient's physical and psychological well-being. Also, because many of these
      drugs are associated with physiological or psychological dependency, it also
      becomes important to identify and treat drug abuse and chemical dependency, which
      is a primary problem in a subgroup of chronic pain patients. This discussion will
      focus on the relationship of drug use to chronic pain behavior and methods of
      medication withdrawal. In addition, the problems of chemical dependency and its
      identification and management will be discussed.J Orthop Sports Phys Ther
      1984;5(6):315-317.

PMID- 18806390
TI  - Determination of a fatigue curve as a function of electromyography and mechanical
      work.
AB  - The purpose of this study was to identify a fatigue curve in which muscle
      electrical activity was a function of the mechanical work performed by the
      anterior tibialis muscle. A work fatigue curve was determined to be the function
      of a cubic regression equation. The work fatigue curve was compatible with the
      accepted physiological concept of at least two different muscle fiber types.J
      Orthop Sports Phys Ther 1984;5(6):332-335.

PMID- 18806391
TI  - Body composition assessment and methodology in nonathletic and athletic
      adolescent and adult males and females.
AB  - The purpose of this review is to outline methodology for assessing body
      composition utilizing anthropometric and densitometric techniques. The objective
      of body composition assessment is to measure body fat and lean body mass. The
      quantity of these components varies due to growth, physical activity, dietary
      regimens, and aging. Anthropometric techniques incorporate selected skinfolds,
      circumferences, skeletal widths, or other variables to estimate body composition
      within k2.0-4.0%. These techniques are adequate for field testing of groups or
      individuals, but are population specific. Densitometry measures body volume
      irrespective of physique, sex, or age. This laboratory technique estimates body
      composition within 1.0-2.0%, is more difficult to administer, but is not
      population specific. Some limitation exists with any present technique due to
      biological variability and incomplete research of reference body composition in
      children, females, and the aged. J Orthop Sports Phys Ther 1984;5(6):336-347.

PMID- 18806392
TI  - Reduction of neuromuscular hypertension for improvement of athletic performance.
AB  - This study investigates the inhibition of neuromuscular tension in specific key
      muscles, for the purpose of increasing athletic efficiency. Four golfers were
      studied electromyographically during the backswing. Integrated EMG findings from
      the right wrist flexors showed a significant decrease following application of
      passive stretch. The theoretical and practical aspects of this technique are
      discussed. J Orthop Sports Phys Ther 1984;5(6):384-390.

PMID- 18806393
TI  - Maximizing equipment utilization in orthopedic and sports medicine
      rehabilitation.
AB  - Much of today's rehabilitative equipment is overpriced and underutilized. This
      paper introduces some alternative equipment combinations and patient-equipment
      position variations in an effort to increase utilization. The U. B.X. T. and Mini
      Gym can be most effectively used in combination for upper extremity
      rehabilitation while the U.B.X. T. and Orthotron provide numerous possibilities
      for upper and lower extremity exercising. Position and pattern variations are
      feasible and offer increased versatility. The clinician is encouraged to
      experiment with this information and seek out the most efficient and productive
      use of available equipment.J Orthop Sports Phys Ther 1984;5(6):373-381.

PMID- 18806394
TI  - Comparison of voluntary and electrical stimulation contraction torques*.
AB  - Informed male volunteers completed maximal isometric knee extension efforts under
      each of three contraction conditions: 1) voluntary, 2) electrical stimulation
      (ES) only, and 3) superimposed (ES superimposed onto voluntary). Ten subjects
      completed the three contraction conditions using each of the following current
      formats: 1) asymmetrical biphasic rectangular wave, 2) asymmetrical biphasic
      spike wave, and 3) symmetrical monophasic square wave. Under the voluntary and
      the superimposed contraction conditions no significant differences in mean torque
      were observed between the three current formats. However, under the ES
      contraction condition, the torque associated with the symmetrical monophasic
      square wave was significantly less than that associated with the other two
      current formats. As well, the torque associated with the asymmetrical biphasic
      spike wave was significantly less than that associated with the asymmetrical
      biphasic rectangular wave format. No significant difference was observed between
      the maximum voluntary contraction (MVC) and the superimposed contraction
      conditions for the groups receiving the asymmetrical biphasic spike and the
      symmetrical monophasic square wave current formats, or between all three
      contraction conditions for the group receiving the asymmetrical biphasic
      rectangular wave format. However, the ES condition was associated with
      significantly less torque than were the MVC and the superimposed conditions for
      the asymmetrical biphasic spike and the symmetrical monophasic square wave
      formats. In response to a posttest questionnaire, 18 of 30 subjects felt that the
      ES contraction produced greater torque than did MVC, and 26 subjects selected the
      superimposed condition as having produced greater torque than the ES condition.
      The different current formats, resulting in different levels of sensation and
      preception, and the different output capabilities of each electrical stimulator
      are considered to have been jointly responsible for the ES only torque
      discrepancies. It is suggested that ES does not recruit more motor units,
      resulting in a greater force of contraction, than are recruited under MVC.J
      Orthop Sports Phys Ther 1984;5(6):324-331.

PMID- 18806395
TI  - Chronic pain: the nature of the problem.

PMID- 18806396
TI  - Chronic pain: basic assumptions - regarding treatment.

PMID- 18806397
TI  - Choices for dealing with chronic pain.

PMID- 18806398
TI  - Legitimizing chronic pain.

PMID- 18806399
TI  - Alphabet spelling exercises for the wrist and hand.
AB  - This article presents a relatively simple active range-of-motion program for the
      wrist and hand which can be utilized by a variety of patients.J Orthop Sports
      Ther 1984;5(6):382-383.

PMID- 18806400
TI  - The management of the chronic pain patient: clinical considerations.
AB  - Virtually everyone has experienced pain and it is reasonable to assume that
      individuals have sought out healers for pain since prehistoric times. There is an
      extensive literature about pain covering its definition, anatomy, physiology,
      psychology, and means of relieving it. However, it appears safe to say that the
      most significant advances have occurred during the last 25 to 30 years. Here, we
      will be concerned with the treatment of patients whose pain has been present six
      months or longer and which is not the result of a life-threatening or function
      threatening disease process. Such pain is generally referred to as chronic
      benign, pain. At the present time, there are an increasing number of programs
      designed to deal with this problem, and health care providers are becoming more
      sophisticated in their understanding of chronic pain syndromes. In the material,
      which follows, the complexities of the problem are detailed from a
      multidisciplinary but integrated point of view.J Orthop Sports Phys Ther
      194;5(6):305-307.

PMID- 18806401
TI  - The use of standardized evaluation forms in physical therapy.
AB  - The need for a consistent and efficient method of patient evaluation is not a new
      one. Standardized evaluation forms that include body charts can be useful in
      recording subjective and objective data in a systematic way. At the Physical
      Therapy Unit- Student Health Center, University of Wisconsin-La Crosse, we have
      designed and put into use this type of evaluation form. We feel these evaluation
      forms allow us to perform consistent and efficient patient evaluations in a short
      amount of time, especially for acute musculoskeletal injuries. A method of
      controlling consistency is very important because of physical therapy and
      athletic training students and interns that rotate through the Physical Therapy
      Unit. Because of the large volume of patients we see, there is a need for
      reducing the amount of time needed in longhanding subjective, objective,
      assessment, and planning (S.O.A.P.) notes. The standardized evaluation forms are
      an efficient alternative to the longhand S.O.A.P. note.J Orthop Sports Phys Ther
      1984;5(6):348-372.

PMID- 18806402
TI  - The influence of hallux extension on the foot during ambulation.
AB  - A review of the literature, focusing on functional anatomy of components of the
      foot/ ankle complex, provides the rationale for normal hallux extension being a
      rehabilitation goal when treating patients with foot dysfunction. Hallux
      extension of 60 to 65 has been found to assist in transforming the foot into the
      rigid lever necessary for gait, allow the hallux and first metatarsal head to
      support normal weightbearing loads, and facilitate flexor hallicus longus action
      during gait. J Orthop Sports Phys Ther 1984;5(5):240-242.

PMID- 18806403
TI  - The effect of physical activity on ligamentous strength: an overview*.
AB  - A brief review of the literature pertaining to the strengthening of ligamentous
      tissue through physical activity is presented. Although literature exists
      supporting both sides of the question, the predominence of evidence seems to be
      in favor of improved ligamentous strength following physical activity. Despite
      the general agreement, the exact mechanism involved is unclear. It is also
      unclear whether the ligament or the ligament-bone interface is the site of
      increased strength. A review of the possible mechanisms involved, as well as a
      discussion of the influence of immobility on the validity of the experimental
      results, is presented. J Orthop Sports Phys Ther 1984;5(5):275-277.

PMID- 18806404
TI  - A biomechanical analysis of the knee joint undergoing rehabilitation: a case
      study.
AB  - The purpose of this study was to use cinematographic methodology for the
      biomechanical analysis of the knee joint as the joint underwent rehabilitation
      following surgical repair of the ligament structure. The biomechanical variables
      consisted of time percent values for four phases of a single gait cycle, velocity
      profiles of knee joint motion, and dynamic force determinations. These variables
      were evaluated prior to and at 3-week intervals during a 9-week rehabilitation
      program. The results found identifiable changes in each of the variables. J
      Orthop Sports Phys Ther 1984;5(5):261-264.

PMID- 18806405
TI  - Use of elbow dynasplint for reduction of elbow flexion contractures: a case
      study.
AB  - A severe elbow flexion contracture following a supracondylar fracture in a 13
      yearold- male was treated with conventional physical therapy and an adjustable
      dynamic splint, the elbow Dynasplint(R). The Dynasplint was applied primarily at
      night. The patient achieved complete resolution of his flexion contracture. The
      Dynasplint incorporates the principles of adjustable, low-intensity force for
      prolonged durations of time.J Orthop Sports Phys Ther 1984;5(5):269-274.

PMID- 18806406
TI  - Norms for high school football players derived from cybex data reduction
      computer.
AB  - Three hundred and forty-two male high school football players, ranging in age
      from 15 to 17, were screened for muscular imbalances and joint abnormalities
      about the knee using a Cybex II lsokinetic Dynamometer and Cybex Data Reduction
      Computer. Each player was tested at speeds of 60, 240, 300 degrees , and 300" per
      second for muscular work. The athletes were classified by position (quarterback,
      runningback, tight end, wide receiver, linemen, linebacker, and defensive back).
      Several parameters were reported: peak torque with gravity effect for both
      extensors and flexors, peak torque to body weight, opposing muscle group ratios,
      torque acceleration energy, work over a preselected number of repetitions,
      endurance ratio, and agonist-antagonist work ratios. The purpose of the screening
      was to provide data beneficial for the prevention of injury from muscular
      imbalance and joint instability, data useful as clinical guidelines for
      rehabilitation and return to play, and suggestions for strength training
      programs. Previous articles have been published showing peak torque, and
      quadriceps and hamstring ratios, as a means of preventing injury due to muscular
      imbalance. However, until the introduction of the Cybex(R) Data Reduction
      Computer, authors had no way of taking the effect of gravity on the lower limb
      into consideration when presenting their findings. Hamstring-quadricep ratios,
      once thought to be ideal at 60% or better at 60 degrees per second are now better
      set at 50 to 55% with gravity effect at 60 per second. The intent of this paper
      is not to draw any specific conclusions but to present meaningful data for the
      purpose of preseason screening to prevent injuries and to aid in strength
      training programs.J Orthop Sports Phys Ther 1984;5(5):243-245.

PMID- 18806407
TI  - Therapeutic Ultrasound: Its Effects on the lntegrity of a Nonpenetrating Wound*.
AB  - This study investigated the effect of ultrasound applied to traumatized muscle
      tissue of an adult male rat. Sixty-six rats were traumatized, treated, and
      sacrificed. The rats were assigned to one of 11 groups, to which experimental and
      control (two mock) ultrasound treatments were given at 3- and 7-minute time
      periods at 0.5 and 1.5 watts per square centimeter intensities (pulsed and
      continuous ultrasound). The rats were given a total of six treatments, once every
      other day three times a week. Treatments began on the third day following the
      receipt of a nonpenetrating wound on the right lateral thigh. The animals were
      subsequently analyzed histologically to determine the extent of healing cells
      present. The principal findings were as follows: 1) ultrasound intensities had a
      significant effect on healing, 2) there was no statistical difference between the
      overall means of the control and experimental groups, and 3) there was no
      difference between the pulsed and continuous modes of ultrasound or between
      treatment times.J Orthop Sports Phys Ther 1984;5(5):278-281.

PMID- 18806408
TI  - A case study: lennox hill bracing for postoperative total knee replacement.
AB  - Traditionally, the use of the Lennox Hill derotation brace has primarily been for
      the management of sports related injuries. From the professional to the weekend
      athlete, or the patient who must return to a demanding occupation, the Lennox
      Hill brace has been utilized preoperatively and/or postoperatively to manage
      various knee disorders. In this case report, the Lennox Hill derotation brace was
      employed to manage post-total knee replacement pain and instability in a
      geriatric patient. Of particular interest in this case, also, is an increase in
      quadriceps strength with the Lennox Hill brace being worn versus quadriceps
      strength with traditional hinge bracing and without brace being worn.J Orthop
      Sports Phys Ther 1984;5(5):265-268.

PMID- 18806409
TI  - Leg length discrepancy assessment: accuracv and precision in five clinical
      methods of evaluation*.
AB  - Five clinical methods of leg length discrepancy assessment were tested against
      one another for their relative accuracy and precision compared to exact
      anatomical standards as determined by radiograph. Five normal subjects, one with
      a known discrepancy of 1.3 cm, were evaluated by twenty physical therapists each
      using every method of assessment. T-tests and F-tests (a = 0.05) were used to
      determine statistical accuracy and precision among methods. Absolute values of
      mean differences, standard deviations, and ranges were used to determine clinical
      significance. The indirect method, which employed lift blocks under a foot with a
      subject in the standing position, proved to be the most accurate and precise
      method of any tested. Of the direct methods tested, which employ a tape measure
      between various anatomical landmarks, the technique shown to be the most accurate
      and precise utilized the landmarks of the anterior superior iliac spine and the
      lateral malleolus of the fibula.J Orthop Sports Phys 1984;5(5):230-239.

PMID- 18806410
TI  - lsokinetic Evaluation of the Ankle lnvertors and Evertors*.
AB  - The purpose of this study was to develop normative strength dues (absolute peak
      torque and relative peak torque) for the ankle inverters and evertors in normal
      adults by using the Cybex dynamometer. Differences in strength between men and
      women, as we// as between dominant leg and nondominant leg, were also compared.
      Absolute peak torque of the two muscle groups in men were significantly higher (p
      < 0.001) than in women. When expressed as relative peak torque, however, only the
      left evertors in men were significantly stronger than the corresponding side in
      women. No Significant difference in strength ( p < 0.01) was found between the
      dominant leg and nondominant leg with the exception of the evertors in women when
      tested at 30 degrees per second. The ratios between the strength of the evertors
      and invertors were also presented; however, no apparent trend was noted. The data
      presented could provide a guideline for rehabilitation of patients.'J Orthop
      Sports Phys Ther 1984;5(5):246-252.

PMID- 18806411
TI  - Head posture: a case study of the effects on the rest position of the mandible*.
AB  - Previous research has shown a relationship between head posture and the rest
      position of the mandible. The purpose in this study was to investigate the
      changes in the resting vertical dimension of the mandible with correction of a
      forward head posture in an edentulous patient. Ten treatments of manual physical
      therapy techniques, such as joint mobilization and muscle stretching to correct
      the forward head posture, were administered. A plumb line test showed an
      improvement of the forward head posture. In addition, the resting vertical
      dimension of the mandible increased an average of 8 millimeters. This result
      suggests that correct head posture may be necessary to precisely calculate the
      resting vertical dimension of the mandible.J Orthop Sports Phys Ther
      1985;5(4):179-183.

PMID- 18806412
TI  - Case studies: isolated strain of the tensor fasciae latae.
AB  - Three cases of isolated strains of the tensor fasciae latae muscle are reviewed.
      Objective and subjective findings, including the differentiation between
      iliotibial band and tensor fasciae latae are discussed. Conservative measures of
      treatment and the technique of stretching the tensor fasciae latae are described.
      The importance of examining this muscle in the evaluation of the contractile
      elements of the hip is stressed.J Orthop Sports Phys Ther 1985;5(4):201-203.

PMID- 18806413
TI  - lsokinetic Quadriceps and Hamstring Torque Levels of Adolescent, Female Soccer
      Players.
AB  - Using a Cybex II(R) dynamometer, the quadriceps and hamstring torque levels of 16
      female high school soccer players were measured. Both the dominant and
      nondominant knees were tested at a fast (1 80 per second) and slow (30 per
      second) speed. The results were similar to those of previous studies that used
      men as subjects. The conclusions were: 1) Extension torque is significantly
      greater than flexion torque for both legs and at both speeds. At 30 per second
      the hamstring1 quadriceps ratio is 0.6 1. This ratio increases to 0.78 at 180 per
      second. 2) There is no significant difference between dominant and nondominant
      legs for either flexion or extension torque at fast or slow speed. 3) At 30' per
      second, peak quadriceps torque is achieved at approximately 73 of extension, and
      peak flexion torque is achieved at approximately 38 flexion. 4) Slow speed
      flexion and extension torque levels are significantly greater than fast speed
      torque levels for both legs.J Orthop Sports Phys Ther 1984;5(4):196-200.

PMID- 18806414
TI  - Comparison of muscle to other soft tissue in limiting elbow extension.
AB  - Nine middle-aged women were examined to determine whether extension of the elbow
      in normal adults is limited primarily by muscle, or by ligaments and capsule.
      Terminal range of elbow extension was measured when the subject was normally
      relaxed and in the same subjects under conditions of paralysis induced by a
      myoneuro blocking agent. Relaxation of the unparalyzed subject was confirmed with
      a biofeedback machine. Paralysis resulted in increased elbow extension in all
      subjects. Since the myoneuro blocking agent affects only muscle and not the
      connective tissue, it is concluded that elbow extension in the normal adult woman
      is limited primarily by muscle.J Orthop Sports Phys Ther 1984;5(4):170-174.

PMID- 18806415
TI  - Flexor hallucis longus tendinitis-a case of mistaken identity and posterior
      impingement syndrome in dancers: evaluation and management.
AB  - Flexor hallucis longus tendinitis and posterior impingement syndrome, two
      problems commonly encountered by dancers, but sometimes misdiagnosed, are
      presented and discussed in terms of anatomy, evaluation, and management.J Orthop
      Sports Phys Ther 1984;5(4):204-206.

PMID- 18806416
TI  - lsokinetic Characteristics of Ballet Dancers and the Response to a Season of
      Ballet Training*.
AB  - Clinical isokinetic characteristics for professional ballet artists were
      determined preseason and at "peak" season. Twenty-eight dancers (equal N/sex)
      were studied at 45, 90, and 180 per second. The data indicated that, while male
      relative torques were similar to other athletes previously reported, the females
      were lower than most other female athletes. With training, males showed virtually
      no change at the slow and intermediate speeds, but improved at 180 per second,
      while females improved at all three speeds but, significantly, only at 180 per
      second. Males generated significantly more torque than females and the torque
      velocity characteristics between sexes were parallel. Clinical characteristics
      showed the dancers to have quadricep balance between legs and proportional
      (hamstrings/quadriceps) within legs (no effects of training on either). The data
      indicates that male dancers have characteristics similar to other athletes, that
      females are lower in relative torque than other female athletes, and that dance
      training affects only torque at functional velocities.J Orthop Sports Phys Ther
      1984;5(4):207-211.

PMID- 18806417
TI  - Pain relief at trigger points: a comparison of moist heat and shortwave
      diathermy.
AB  - This study compared the pain-relieving effects of shortwave diathermy and moist
      heat on trigger points. Patients with trigger points on the neck or back were
      randomly assigned one of these treatments. The sensitivity of each trigger point
      was measured with a pressure algometer before treatment, 5 minutes after
      treatment, and 30 minutes after treatment. Sensitive trigger points, at which
      2000 grams of force or less caused pain, were more responsive to treatment than
      moderate trigger points (painful only at 2000 grams or greater force). Both
      treatments were effective in relieving the pain of sensitive trigger points but
      shortwave diathermy was more effective at decreasing the sensitivity of both
      sensitive and moderate trigger points (P > 0.0581). The pressure algometer was
      shown to be a useful device for objectively measuring pain and may be useful in
      selecting the most effective type of treatment for trigger points.J Orthop Sports
      Phys Ther 1984;5(4):175-178.

PMID- 18806418
TI  - Hamstrung by hamstring strains: a review of the literature*.
AB  - The purpose of this paper is to review those studies which have attempted to
      delineate causative factors of hamstring strains. Anatomy and biomechanics of the
      hamstring muscle group are reviewed. Mechanisms of injury and various etiological
      factors are presented. Decreased hamstring muscle flexibility and decreased
      hamstring muscle strength were factors most frequently studied, yet the
      relationship of these factors to the incidence of hamstring strains remains
      unclear. Future studies should seek to test hamstring muscle flexibility and
      strength under conditions simulating the proposed mechanisms of injury. Results
      of further research examining decreased hamstring muscle flexibility and strength
      must be viewed in light of age, levels of maturity, history of previous injury,
      demands of specific activities, and psychological characteristics of the
      participants.J Orthop Sports Phys Ther 1984;5(4):184-195.

PMID- 18806419
TI  - A case study: the importance of a dynamic evaluation in the assessment of
      posterior knee pain.
AB  - To evaluate and treat knee problems, it is important to have an understanding of
      the functional anatomy of the structures about the knee joint. Injuries involving
      the musculature that insert or originate about the knee can cause pain leading to
      loss of function. The gastrocnemius muscle, primarily a plantarftexor of the
      ankle; is also a flexor of the knee joint due to its origin just above the
      lateral and medial femoral condyles on the posterior surface of the femur.' The
      following case report is of a strain to the medial head of the gastrocnemius
      which resulted in pain located at the posteriormedial region of the knee. A
      differential test to distinguish between a lesion of the gastrocnemius and the
      posterior capsule of the knee is presented.J Orthop Sports Phys Ther
      1983;5(3):132-133.

PMID- 18806420
TI  - Contribution of neural and muscular factors to the short duration tension-
      developing capacity of skeletal muscle.
AB  - Neural and muscular factors contributing to the short duration tension-developing
      capacity of muscle are reviewed. Among the neural factors discussed are pyramidal
      tract activity, and the order, extent, frequency, and synchrony of motor unit
      recruitment. Muscular factors included within the review are muscle size, fiber
      type, and fiber number. Alterations in neural and muscular factors that accompany
      training are also presented as are the interactions between them.J Orthop Sports
      Phys Ther 1983;5(3):139-147.

PMID- 18806421
TI  - Rehabilitation for anterior cruciate reconstruction.
AB  - The rising number of knee ligament injuries which are subsequently surgically
      reconstructed require special rehabilitation programs. Casting is followed by a
      knee brace with careful attention paid to restricting full extension. A complete
      rehabilitation program must include provisions for strengthening knee muscles
      without placing excess stress on the surgical repair. This program must be
      coupled with a gradual increase in weight bearing and rigorous control of knee
      position to yield the optimal result.J Orthop Sports Phys Ther 1983;5(3):121-126.

PMID- 18806422
TI  - Gait analysis with reference to chondromalacia patellae.
AB  - This study analyzed the gait of women exhibiting symptoms of chondromalacia
      patellae, and compared them with a group of women without chondromalacia
      symptoms. High speed cinematography was used to film the subjects walking on a
      level surface and a 15 downhill slope. Flexion of the knee on both surfaces
      during the single support phase was significantly less for the chondromalacia
      subjects (P < 0.05). increased external femoral rotation was detected in
      chondromalacia patellae subjects (P < 0.05) during swing phase on level and
      sloping surfaces. A radical inward femoral rotation occurred immediately
      preceding heel strike (P < 0.001). We conclude that significant differences in
      gait are apparent in females exibiting chondromalacia patellae symptoms as
      compared with apparently normal female knees.J Orthop Sports Phys Ther
      1983;5(3):127-131.

PMID- 18806423
TI  - Case study: superior tibiofibular joint.

PMID- 18806424
TI  - Wrist and hand examination and interpretation.
AB  - Hand rehabilitation is an area with the potential for providing orthopaedic
      physical therapists a challenging and rewarding practice. However, success in
      treating the patient with hand dysfunction is closely associated with the
      therapist's understanding of essential anatomic and pathokinesiologic principles
      and the related ability to adequately evaluate, plan, and perform treatment. The
      first article (Wadsworth CT: Clinical anatomy and mechanics of the wrist and
      hand. J. Orthop Sports Phys Ther 4:205-216) in this two-part series covered the
      background anatomic and pathokinesiologic concepts. This, the second article of
      the series, describes the format for examination of the patient with hand
      dysfunction and presents a practical but comprehensive evaluation form for
      clinical use. It also supplies information for interpretation of the examination
      which lays the foundation for goal setting and treatment planning.J Orthop Sports
      Phys Ther 1983;5(3):108-120.

PMID- 18806425
TI  - Heel counter stabilization of the running shoe.
AB  - A simple and effective way to increase the stability of both running shoes and
      the rearfoot is to fabricate a heel counter stabilizer. Heel contact is the first
      aspect of stance phase during gait and is an extremely critical time for the
      running foot. The runner generally lands on the outside portion of the heel and
      rolls to a level position. Depending upon the runner's anatomical and functional
      variations, the foot may not roll far enough (excessive supination), or roll too
      far (excessive pronation). These actions tend to breakdown the rear of the
      running shoe, and rearfoot control is lost. Rearfoot control is of utmost
      importance for proper shoe wear, sound running mechanics, and injury prevention.
      The heel counter is responsible for rearfoot stability. This is located in the
      rear of the shoe under the foxing, which extends laterally and medially to the
      corresponding longitudinal arch. It is typically made of cardboard or a type of
      plastic. If this is broken down, calcaneal valgus or varus could result, leading
      to a multitude of potential lower extremity injuries (i.e., plantar fascitis,
      posterior tibialis tendinitis, patellofemoral dysfunction), as well as the
      investment loss of the shoes. The technique described will give additional
      support to the heel counter. It can be used to prevent the counter from breaking
      down, or to correct an already destroyed counter. However, discretion should be
      used as not all heel counters are salvageable. The procedure is a nonconsuming
      endeavor utilizing materials common to most physical therapy departments,
      training rooms, or private clinics. J Orthop Sports Phys Ther 1983;5(2):82-83.

PMID- 18806426
TI  - The effect of stretching on the range of motion of the ankle joint in badminton
      players*.
AB  - The range of motion in the ankle joints were studied in two groups of badminton
      players during their training season. In one group, the exercise program
      consisted of tip-toe raising, whereas in the other group stretching exercise was
      added. The range of motion in the ankle joint in badminton players did not
      deviate from that of a control group. Both programs, stretching as well as
      regular exercise, increased the range of motion by approximatively 5 degrees
      during a 12-week period. No lengthening of the gastrocnemius muscle could be
      measured under maximal dorsiflexion from 30-35'. Too short or too tight a calf
      muscle does not explain the high incidence of Achilles tendon rupture and
      Achilles tendon pain in badminton players.J Orthop Sports Phys Ther 1983;5(2):74
      77.

PMID- 18806427
TI  - A case study: the accessory soleus.
AB  - A 16-year-old girl was complaining of soft swelling on the antero-medial aspect
      of the Achilles tendon, resembling a soft tissue tumor. She was asymptomatic on
      normal activity, but running and jumping produced an aching pain. Surgical
      exploration revealed an accessory soleus muscle and excision resulted in complete
      relief of the symptoms. J Orthop Sports Phys Ther 1983;5(2):84-85.

PMID- 18806428
TI  - Survey of scholastic athletic health care and sports medicine clinics.
AB  - The increasing number of athletes requiring health care has spurred the growth of
      the development of sports medicine clinics. The diversity of such clinics is
      readily apparent. These clinics primarily function to provide evaluative and
      rehabilitative measures to all groups of athletic participants. Scholastic health
      care for athletic participants has not proceeded in a similar pattern. Sports
      medicine clinics are not effectively meeting the needs of the scholastic athlete,
      primarily because of location and financial limitations. This survey was
      conducted to collect information to further delineate the problems associated
      with scholastic health care of athletic participants. It appears that sports
      medicine clinics are manned by several levels of health care professionals.
      Scholastic athletes are least adequately covered by insurance and also suffer
      from being within a somewhat isolated environment. The need for on-field care and
      follow-up care within the school system remains a key problem associated with
      scholastic health care. Further research into the relationship of insurance
      policies which will adequately meet the needs of the scholastic population must
      be pursued. J Orthop Sports Phys Ther 1983;5(2):78-81.

PMID- 18806429
TI  - Angular Specificity and Test Mode Specificity of Isometric and lsokinetic
      Strength Training *.
AB  - This study examined the angular specificity and test mode specificity of strength
      training. Six males and six females (X = 22.6 years) were assigned to groups
      which trained either isometrically (90 degrees ) or isokinetically (30 degrees
      /second). They trained their left elbow extensors at 80% of their maximum
      voluntary contraction on a modified Cybex(R) apparatus for 10 weeks, three
      sessions per week, with 50 contractions per session. Before and after training,
      both groups were tested isometrically (70, 90, 110 degrees ) and isokinetically
      (30 degrees /second). When tested isometrically, both groups improved equally,
      and strength was increased at all three test angles to about the same extent.
      When tested isokinetically, both groups improved, but the isokinetic group
      improved to a greater extent. In conclusion, no angular specificity of training
      was demonstrated within 20 degrees of the training angle, and no test mode
      specificity was seen for isometric testing. However, isometric training showed
      less transfer to an isokinetic test. J Orthop Sports Phys Ther 1983;5(2):58-65.

PMID- 18806430
TI  - Review of physiological effects of cryotherapy.
AB  - The purpose of this work is to provide the physical therapist with the research
      documented conclusions that he would find if he were to review the literature on
      the physiological effects of cold therapy. The conclusions are that the results
      of the studies reviewed were consistent in describing reductions in
      musculoskeletal pain, spasm, connective tissue distensibility, intramuscular
      temperature, nerve conduction velocity, and spasticity (except the initial
      seconds of application). Other conclusions are that the results of the studies
      reviewed were inconsistent in describing the changes in swelling, blood flow,
      heart rate, blood pressure, intraarticular temperature, rheumatoid arthritis,
      monosynaptic reflex, and the muscle spindle.J Orthop Sports Phys Ther
      1983;5(2):66-73.

PMID- 18806431
TI  - The semi-flexible foot orthotic: fabrication and guidelines for use.

PMID- 18806432
TI  - Delayed muscle soreness: a review.
AB  - There are two generally recognized types of muscular pain or soreness associated
      with severe exercise. These two types are a) acute soreness and b) delayed
      soreness. Acute soreness or pain occurs during and immediately following
      exercise. This condition is short-lived and is alleviated when exercise is
      discontinued. Acute soreness is thought to be associated with lack of adequate
      blood flow or ischemia to the active muscles. The more serious problem associated
      with severe exercise is delayed muscle soreness, i.e., pain and soreness that
      occurs 24 to 48 hours after exercise. Four popular theories of the etiology of
      this condition are: lactic acid accumulation, spasms, torn tissue, and connective
      tissue damage. These theories are discussed in light of current biochemical and
      morphological findings. From recent studies designed to induce delayed soreness,
      it has been found that the degree of delayed soreness experienced with exercise
      is related to the type of muscle contraction performed. Maximum soreness is
      associated with eccentric types of contractions. A possible explanation for this
      finding is presented.J Orthop Sports Phys Ther 1983;5(1):10-13.

PMID- 18806433
TI  - The construction and implementation of functional progressions as a component of
      athletic rehabilitation.
AB  - Physical therapists are becoming increasingly visible as contributing members of
      sports medicine teams. Secondary to this public awareness, many physical
      therapists with minimal athletic backgrounds may be called upon to prepare a
      seriously injured athlete for competition. It is the purpose of this paper to
      introduce the physical therapists to the construction, implementation, and
      benefits of functional progressions as utilized as an augmentation to athletic
      rehabilitation.J Orthop Sports Phys Ther 1983;5(1):14-19.

PMID- 18806434
TI  - The cobra pad-an orthotic alternative for the physical therapist.
AB  - This article provides the physical therapist with a practical way to construct a
      functional orthotic device in the clinic. The procedure explained requires a
      minimal amount of supplies and can be easily fabricated during the patient's
      treatment session.J Orthop Sports Phys Ther 1983;5(1):30-32.

PMID- 18806435
TI  - Osteoid osteoma: a diagnostic problem.
AB  - A 32-year-old patient is presented to draw the attention of physical therapists
      to the diagnosis of osteoid osteorna, particularly in patients after an athletic
      injury. Osteoid osteorna is a benign neoplasm, but it can cause substantial pain
      and disability. This paper is not intended to add another case to the 400 already
      published, but rather to point out the difficulty in diagnosing osteoid osteorna
      despite modern laboratory findings and a classical history of pain responsive to
      salicylates only. Surgical excision of an osteoid osteorna, if diagnosed and
      present, is always indicated. It brings complete relief and eliminates any
      further need for physical therapy. In order to be certain that the nidus is
      excised, an x-ray of the specimen should be taken. J Orthop Sports Phys Ther
      1983;5(1):33-35.

PMID- 18806436
TI  - Descriptive analysis of quadriceps and hamstrings muscle torque in high school
      football players*.
AB  - The purpose of this study was to establish a range of acceptable torque values
      for competition in high school football. The results indicated that body weight
      can be used as an acceptable predictor of lower extremity muscular torque.
      Therefore, it was concluded that body weight can be utilized to produce an
      average range of desirable torque values for participation in high school
      football.J Orthop Sports Phys Ther 1983;5(1):2-6.

PMID- 18806437
TI  - The definition and assessment of muscular power.
AB  - Considerable confusion still exists in the sports medicine literature concerning
      the measurement of muscular power and what it represents. Measures of muscular
      performance cannot be conveniently categorized as "strength " or ''power" on the
      basis of the contractile velocity employed in the performance task. Given the
      proper physical definitions and formulations involved in muscular power
      measurement, it is concluded that although strength (force output) and power
      (work/time) are quantitatively related, they remain separate physical parameters
      that can be measured in all dynamic muscular contractions, whether fast or slow.
      J Orthop Sports Phys Ther 1983;5(1):7-9.

PMID- 18806438
TI  - The adolescent athlete: a musculoskeletal update.
AB  - Adolescent athletes are participating in new and popular sports. What are today's
      musculoskeletal concerns for these athletes? The purpose of this paper is to
      provide an update on what is currently known about the young athlete and how
      contributing factors of injury have changed accordingly. Preventative measures
      are included. A review of recent literature and discussions of the relevant
      anatomical concerns (musculoskeletal), issues and trends in sport, and sport
      medicine philosophies are provided. The summary suggests that because adolescent
      athletes are being exposed to new sports in different ways, critical questions
      concerning the effects of sports are essential to insure a safer athletic
      environment.J Orthop Sports Phys Ther 1983;5(1):20-25.

PMID- 18806439
TI  - Protocol for strength testing and rehabilitation of the upper extremity.
AB  - The development of the upper body table (UBXT) provided trunk and pelvis
      stabilization, necessary for accurate testing of the strength (and power) of the
      upper extremity with the Cybex II(R) lsokinetic Dynamometer; however, a standard
      protocol for set-up and testing did not immediately exist in 1979. During
      treatment of patients with upper extremity problems, Sportclinic, Providence
      Medical Center, Seattle, Washington, developed a complete protocol for
      rehabilitation and testing with the Cybex II and the UBXT, using fast speeds, a
      90-foot-pound torque scale, and special adaptations of equipment and procedure.
      The objectives of the protocol were to increase accuracy in testing and decrease
      the chance of injury to the patient J Orthop Sports Phys Ther 1983;4(4):229-235.

PMID- 18806440
TI  - Axial rotation of the knee in women.
AB  - Eighty-five women with normal left knees were measured to determine the active
      axial rotation that is normally present at the tibiofemoral joint. Subjects were
      seated with the leg perpendicular to a measuring platform placed at floor level
      and rotation was measured with the knee flexed at 70, 90, and 110 degrees . Mean
      total rotation was found to increase from 35 to 40 to 44 degrees as the knee
      flexion angle increased (P < 0.0 1). External rotation from the neutral position
      at all angles of flexion was approximately twice that of internal rotation. These
      values are in general agreement with those obtained in earlier studies, but are
      different from values given in many textbooks. Although precise measurement of
      axial rotation is difficult in a clinical setting, an approximation of
      symmetrical rotation can be made. J Orthop Sports Phys Ther 1983;4(4):236-240.

PMID- 18806441
TI  - Magnetic field therapy-does it affect soft tissue? *.
AB  - Claims that magnetic field therapy improves peripheral circulation and tissue
      oxygenation have been tested on normal volunteers. Transcutaneous oxygen tension
      measurements were made and skin temperatures measured in a double blind trial.
      Using recommended magnetic field configurations, no significant effects
      attributable to the magnetic field therapy could be demonstrated. J Orthop Sports
      Phy Ther 1983;4(4):241-246.

PMID- 18806442
TI  - Measuring wrist muscle strength.
AB  - The purpose of the study was to design and evaluate a clinically acceptable
      method of objectively measuring wrist muscle strength. Static and dynamic wrist
      muscle strength measures for the wrist flexors, extensors, radial deviators, and
      ulnar deviators of 30 college-age students were recorded on the Cybex II(R). The
      Cybex II and testing methods devised for using it demonstrated an acceptable
      consistency of measurement; the average reliability coefficients for the tests
      conducted were r = 0.881 and 0.892. The findings indicate isometric torque and
      low velocity isokinetic torque are highly related. The dominant wrist muscle
      strength was greater than nondominant, but the two measures exhibited similar
      patterns of variance across muscle groups and test speeds. Statically and
      dynamically, the wrist flexors produced the greatest mean, peak torque followed
      by the radial deviators, ulnar deviators, and wrist extensors in decreasing order
      of strength. Aside from cost, the Cybex II and testing method employed proved to
      be a feasible means of objectively measuring wrist muscle strength.J Orthop
      Sports Phys Ther 1983;4(4):217-228.

PMID- 18806443
TI  - Clinical anatomy and mechanics of the wrist and hand.
AB  - Hand rehabilitation is an area with the potential for providing orthopaedic
      physical therapists a challenging and rewarding practice. However, success in
      treating the patient with hand dysfunction is closely associated with the
      therapist's understanding of essential anatomic and pathokinesiologic principles
      and the related ability to adequately evaluate, plan, and perform treatment. This
      article, the first of a two-part series, is intended to provide a working
      knowledge of clinical anatomy, mechanics, and pathology of the wrist and hand.
      Emphasis is placed on the structure and function of parts which commonly limit
      motion, and sufficient information is provided to aid the clinician in performing
      a differential diagnosis and developing treatment rationale. The second part of
      the series will describe a practical method of evaluation and offer treatment
      suggestions for specific disorders.J Orthop Sports Phys Ther 1983;4(4):206-216.

PMID- 18806444
TI  - Angle your cybex recorder for improved results.
AB  - With the growing use of the Cybex II (Lumex Inc., Bay Shore, NY), clinicians have
      developed many ways to ensure maximum results from a patient evaluation. We have
      found that by making a small modification in the placement of the Cybex recorder,
      we can improve the patient's response. By angling the recorder 20 degrees (Fig.
      1) the following changes and potential improvements of the test procedure have
      been seen (Fig. 2): 1 ) the therapist may sit during the test which improves
      patient-clinician eye contact, 2) Hands-on contact is improved, 3) the clinician
      can easily view the recorder, and 4 ) the patient can view the recorder for a
      biofeedback effect. J Orthop Sports Phys Ther 1983;4(3):179-180.

PMID- 18806445
TI  - Treatment Parameters of High Frequency Electrical stimulation as Established on
      the Electro-Stim 180.
AB  - Tremendous interest has developed regarding the use of electrical stimulation in
      both treatment and strengthening regimens. The Electro Stim 180 (Numed, Joliet,
      IL) is manufactured in Canada and imported into the United States. This unit
      functions at 2500 cycles per second with output similar to that developed by a
      Russian electrical stimulation device. A paucity of treatment parameters exists
      regarding this apparatus. Fifteen normal subjects participated in this study to
      establish treatment parameters in an exercise regimen. All subjects (mean age,
      24) were pretreated isometricly and isokineticly in knee extension bilaterally
      using a Cybex II (Cybex, Ronkonkama, NY). The subjects were divided into three
      groups with group one receiving stimulation each day during a 10-day period and
      group two receiving stimulation on alternate days of a 10-day period, while group
      three served as a control. All treatment sessions consisted of 10 isometric
      contractions of 15 seconds duration, interspaced with 50 seconds of rest. Current
      was applied as tolerated to the left knee extensor mechanism during each trial.
      Current accommodation, strength of generated contraction, other associated
      treatment effects and strength differences were recorded. It was concluded that
      the Electro- Stim 180 is capable of generating greater than 60% of the maximal
      isometric voluntary knee extension, that stimulation is somewhat unpleasant, and
      that a tremendous degree of current accommodation is possible. Although strength
      gains were not significant in this particular study, they approached significance
      and, hence, indicate the need for further study in this area.J Orthop Sports Phys
      Ther 1983;4(3):162-168.

PMID- 18806446
TI  - Reliability of lnstrumentation and Measurement Procedures for Active Internal and
      External Tibial Rotation.
AB  - Active internal and external tibial rotation were measured as independent motions
      from a neutral starting position. This study determined the reliability of a new
      instrument and measurement procedure designed to measure tibial rotation.
      Reliability coefficients for internal and external tibial rotation were 0.93 and
      0.8 1, respectively. It was concluded that 1) a neutral rotary position can be
      established from which to measure internal and external rotation, and 2) internal
      and external tibial rotation can be measured reliably.J Orthop Sports Phys Ther
      1983;4(3):154-157.

PMID- 18806447
TI  - The Use of lsokinetics in the Treatment of Chondromalacia Patellae: A Case
      Report.
AB  - The concept of high speed isokinetic rehabilitation for specific training of fast
      twitch fibers is gaining popularity. This concept, in combination with studies
      concerning patellofemoral joint reaction forces, has been utilized to develop a
      treatment protocol for chondromalacia patellae. A case report of the use of high
      speed isokinetic quadriceps strengthening in short arc fashion is presented.J
      Orthop Sports Phys Ther 1983;4(3):176-178.

PMID- 18806448
TI  - Visco-Elastic Orthotics: Sorbothane II.
AB  - The runner is predisposed to anatomical or biomechanical abnormalities when the
      feet strike the ground during the stance phase of running. A force of three to
      eight times the body weight (depending on the running surfaces and the runner's
      weight) is absorbed or transmitted directly to the musculoskeletal system. Recent
      advances in space age technology may have produced a remedy to injuries caused by
      nondissipating forces.J Orthop Sports Phys Ther 1983;4(3):174-175.

PMID- 18806449
TI  - The Relationship between lsokinetic Testing and Dynamic Patellofemoral
      Compression.
AB  - Forty-two knees were tested on both symptomatic and asymptomatic subjects.
      Subjects were tested using dynamic patellofemoral compression tests, and knee
      extension/flexion was evaluated using an isokinetic dynamometer with a dual
      channel recorder. The records of knee extension torque were analyzed using a
      single blind assessment and were judged to be regular or irregular based on
      deflections from the upward or downward course of the torque tracing. A
      statistically significant relationship was found between irregularity of the
      torque records and positive findings on the patellofemoral compression tests
      performed in full knee extension. A similar relationship was present between
      regular torque curves and negative findings on the compression tests. It was
      concluded that assessment of the regularity of the isokinetic torque of knee
      extension is a potentially valuable adjunct to evaluation of persons with
      disorders of the patellofemoral joint, but further research is needed to explore
      this area.J Orthop Sports Phys Ther 1983;4(3):150-153.

PMID- 18806450
TI  - The role of endorphins in exercise: a review of current knowledge.
AB  - Exercise training is used increasingly to prevent and treat disease, and millions
      of healthy persons participate in various aerobic-type sports; yet, the
      mechanisms by which exercise produces various clinical effects is imperfectly
      understood. Emerging evidence suggests that the endogeneous opioid endorphins may
      be involved in two widely varying aspects of exercise: endocrine control and
      behavior and mood adaptation. The present paper summarizes these findings. The
      relationship of endorphins and adrenocorticotropin to stress and the aspects of
      endorphins' involvement in the concept of "runner's high" are discussed. J Orthop
      Sports Phys Ther 1983;4(3):169-173.

PMID- 18806451
TI  - Use of EMG-Derived Slope Coefficient for Determination of Muscle Functional
      Capacity.
AB  - The purpose of this study was to determine if the slope coefficient for the
      linear relationship between EMG voltage time integral and submaximal isometric
      contractions of the vastus medialis muscle could be used as a means for
      evaluating the muscle's functional capacity. It was concluded that the slope
      coefficient provided an objective numerical indicator of muscle functional
      capacity. J Orthop Sports Phys Ther 1983;4(3):158-161.

PMID- 18806452
TI  - Cosmetic products and their current European regulatory framework.

PMID- 18806453
TI  - Challenges related to cosmetic safety assessment in the EU.

PMID- 18806454
TI  - Critical analysis of the safety assessment of cosmetic ingredients performed at
      the European level.

PMID- 18806455
TI  - Safety assessment of cosmetic ingredients present in technical information files
      of finished products.

PMID- 18806456
TI  - The cosmetic technical information file in practice.

PMID- 18806457
TI  - The use of alternative methods in the safety assessment of cosmetic ingredients.

PMID- 18806458
TI  - Headlines of safety assessment of cosmetics in Europe and future perspectives.

PMID- 18806459
TI  - Nutrition and fitness from the first Olympiad in 776 BC to the 21st century and
      the concept of positive health.

PMID- 18806460
TI  - Omega-3 fatty acids, exercise, physical activity and athletics.

PMID- 18806461
TI  - Omega-6 fatty acids and excessive adipose tissue development.

PMID- 18806462
TI  - Non-conventional genetic risk factors for cardiovascular disease.

PMID- 18806463
TI  - ApoE genotype: impact on health, fitness and nutrition.

PMID- 18806464
TI  - Nutrition in the prevention of chronic diseases.

PMID- 18806465
TI  - Exercise and obesity: lifestyle modification as a means in prevention and
      treatment.

PMID- 18806466
TI  - Nutritional risk factors for gastrointestinal cancers: the multiethnic cohort
      study.

PMID- 18806467
TI  - Mediterranean food and diets, global resource for the control of metabolic
      syndrome and chronic diseases.

PMID- 18806468
TI  - The role of government in nutrition and fitness.

PMID- 18806469
TI  - Balancing the scales: a common-sense look at global nutrition problems and what
      can be done about them.

PMID- 18806470
TI  - Historical perspective: the antiquity of exercise, exercise physiology and the
      exercise prescription for health.

PMID- 18806471
TI  - Analysis of C. elegans VIG-1 expression.
AB  - Double-stranded RNA (dsRNA) induces gene silencing in a sequence-specific manner
      by a process known as RNA interference (RNAi). The RNA-induced silencing complex
      (RISC) is a multi-subunit ribonucleoprotein complex that plays a key role in
      RNAi. VIG (Vasa intronic gene) has been identified as a component of Drosophila
      RISC; however, the role VIG plays in regulating RNAi is poorly understood. Here,
      we examined the spatial and temporal expression patterns of VIG-1, the C. elegans
      ortholog of Drosophila VIG, using a vig-1::gfp fusion construct. This construct
      contains the 908-bp region immediately upstream of vig-1 gene translation
      initiation site. Analysis by confocal microscopy demonstrated GFP-VIG-1
      expression in a number of tissues including the pharynx, body wall muscle,
      hypodermis, intestine, reproductive system, and nervous system at the larval and
      adult stages. Furthermore, western blot analysis showed that VIG-1 is present in
      each developmental stage examined. To investigate regulatory sequences for vig-1
      gene expression, we generated constructs containing deletions in the upstream
      region. It was determined that the GFP expression pattern of a deletion construct
      (delta-908 to -597) was generally similar to that of the non-deletion construct.
      In contrast, removal of a larger segment (delta-908 to -191) resulted in the loss
      of GFP expression in most cell types. Collectively, these results indicate that
      the 406-bp upstream region (-596 to -191) contains essential regulatory sequences
      required for VIG-1 expression.

PMID- 18806473
TI  - Patterns of natural selection at the Alcohol dehydrogenase gene of Drosophila
      americana.
AB  - Similar outcomes are often observed in species exposed to similar selective
      regimes, but it is unclear how often the same mechanism of adaptive evolution is
      followed. Here we present an analysis of selection affecting sequence variation
      in the Alcohol dehydrogenase (Adh) gene of Drosophila americana, a species
      endemic to a large climate range that has been colonized by D. melanogaster.
      Unlike D. melanogaster, there is no evidence of selection on allozymes of ADH
      across the sampled range. This indicates that if there has been a similar
      adaptive response to climate in D. americana, it is not within the coding region
      of Adh. Instead, analyses of a combined dataset containing 86 alleles of Adh
      reveal purifying selection on the Adh gene, especially within its intron
      sequences. Frequency spectra of derived unpreferred variants at synonymous sites
      indicate that these sites are affected by weak purifying selection, but the
      deviation from neutrality is less drastic than observed for derived variants in
      noncoding introns. This contrast further supports the notion that noncoding sites
      in Drosophila are often subject to stronger selection pressures than synonymous
      sites.

PMID- 18806472
TI  - Controlling histone methylation via trans-histone pathways.

PMID- 18806474
TI  - Need for neck dissection after radiochemotherapy? A study of the French GETTEC
      Group.
AB  - BACKGROUND/HYPOTHESIS: The need for a neck dissection after radiochemotherapy
      (RCT) for patients with unresectable cancer of the head and neck remains
      questionable. We evaluated our strategy to perform a neck dissection in patients
      with a controlled primary tumor based on the response to RCT according to
      regional control, survival rates, and morbidity. STUDY DESIGN: The French "Groupe
      d'Etude des Tumeurs de la Tete et du Cou" (GETTEC) group retrospectively
      performed a multicenter review. One hundred and three stage III (N = 7) or IV (N
      = 96) patients with unresectable primary tumors and node-positive disease and no
      distant metastases treated between 1996 and 2002. Tumors were considered
      unresectable or with poor surgical curability based on advanced stage, or
      patients were surgically unfit for medical reasons. RESULTS: With a median follow
      up of 30 months, the complete clinical and radiological nodal response rate was
      61%. Among 39% (N = 40) of patients with residual neck disease, 70% (N = 28)
      underwent a neck dissection, whereas the remaining 30% either underwent watchful
      follow-up for probable scary nodes, or were deemed unresectable or medically
      unfit for surgery. Half of the neck dissection specimens showed pathological
      evidence of viable tumor. Grade 3 to 4 complications were recorded in four
      patients (14%) after neck dissection. Regional control was better for complete
      responders. Disease-free survival and overall survival were similar between
      patients with a complete response in the neck and no neck dissection, and
      patients with a neck dissection for residual neck disease. CONCLUSIONS: The
      strategy to avoid a neck dissection is safe in patients with a complete response
      in the neck, regardless of initial nodal stage. In patients with residual neck
      disease, postRCT neck dissection can be performed with limited morbidity.
      Progress is warranted to optimize the pathological response in the nodes and to
      better assess ambiguous nodal responses with multi-modal imaging.

PMID- 18806475
TI  - Quality of life measures and predictors for adults with unilateral vocal cord
      paralysis.
AB  - OBJECTIVE/HYPOTHESIS: To investigate the quality of life (QoLF) status of
      Taiwanese adults with unilateral vocal cord paralysis (UVCP). STUDY DESIGN: A
      prospective, QoLF survey in a tertiary referral voice center. METHODS: Fifty-five
      consecutive UVCP patients were evaluated with Medical Outcome Study Short Form-36
      (SF-36) Health Survey and the voice outcome survey at entry. RESULTS: UVCP
      patients have significantly lower scores in all eight SF-36 subscales (P < .05)
      than do normative Taiwan adult population, particularly in role functioning
      physical problems, social functioning, and role functioning-emotional problems.
      Shimmer parameter is a robust and consistent predictor for bodily pain (beta = 
      20.8), role functioning-emotional problems (beta = -27.9), and social functioning
      (beta = -20) general health dimensions. Shimmer is also predictive of UVCP
      related total voice outcome survey score (beta = -8.6, P < .05). CONCLUSIONS:
      UVCP can seriously compromise phonation, swallowing, and social functions; thus
      significantly impacting a patient's general health status. Voice physiological
      function is also a QoLF outcome indicator.

PMID- 18806476
TI  - Minimally invasive pituitary surgery.
AB  - OBJECTIVES/HYPOTHESIS: Surgical approaches to the pituitary have undergone
      numerous refinements over the last 100 years. The introduction of the endoscope
      and the advent of minimally invasive pituitary surgery (MIPS) have revolutionized
      pituitary surgery. This study aims to compile and evaluate outcomes of all of the
      MIPS performed at our institution. STUDY DESIGN: Retrospective, cases series of
      176 consecutive patients undergoing MIPS. METHODS: Patient demographics, tumor
      characteristics, and intraoperative or postoperative complications for of 176
      consecutive patients undergoing MIPS were complied. Statistical analysis for
      categorical variables and incidence across series were conducted using Pearson's
      chi test and Fisher's exact tests. Odd ratios were calculated to relate the
      discrete variables to outcomes and designing clinical prediction of risk.
      RESULTS: One hundred seventy-six patients who underwent 193 procedures.
      Pathologic evaluation revealed 147 of the tumors to be pituitary adenomas. Only
      one death occurred (mortality rate of 0.5%). The rate of diabetes insipidus
      occurred in 20.2% of the procedures. Vascular complications occurred in 5.2% of
      the procedures. Intraoperative cerebrospinal fluid (CSF) leaks were identified in
      19.7% whereas postoperative CSF leak was noted in 10.3%. Resection of Rathke's
      cleft cyst correlated higher risk of both intraoperative and postoperative CSF
      leak (OR = 2.6, P <.001). Resection of tumors other than adenomata correlated
      with significantly higher risk of CSF leak (OR = 9.0, P = <.001). Sinusitis
      occurred after eleven resections (5.7%). Meningitis occurred in 2 of 193
      resections (1.0%) in our series. Two neurologic complications occurred in our
      series, pneumocephalus and cranial neuropathy (1.0%). No other complications
      occurred. CONCLUSIONS: MIPS is a safe and efficacious marriage of the endoscope
      to the transsphenoidal approach. Thus, a brightness and clarity of vision is
      combined with the unique ability to explore the tumor bed with angled views and
      hydroscopy. Outcomes and complication rates comparable to traditional
      transsphenoidal approaches have resulted but with less dissection and tissue
      manipulation, reduced need for packing, and greater patient comfort and
      acceptance.

PMID- 18806477
TI  - Acoustic trauma augments the cochlear immune response to antigen.
AB  - OBJECTIVES/HYPOTHESIS: To test whether noise-exposure, which activates a cochlear
      immune response with cytokine expression and infiltration of circulating
      leukocytes could augment the response to antigen (Ag). STUDY DESIGN: Randomized,
      prospective, mice. METHODS: We sensitized mice to an Ag, injected it
      intrathecally, and subsequently exposed the mice to noise (8-16 kHz, 90, 100, or
      118 dB for 2 hours). Control mice received either noise exposure alone (100 or
      118 dB), Ag challenge alone, intrathecal surgery and phosphate-buffered saline
      injection or no treatment. Four hours or 7 days later the mice were killed and
      cochlear sections were evaluated immunohistochemically for CD45, ICAM-1, and
      phospho-nuclear transcription factor-kappaB expression. RESULTS: Intrathecal Ag
      injection caused no hearing loss, but did result in a small immune response. Loud
      noise (118 dB) caused severe hearing loss and slight inflammation. The number of
      CD45-positive cells was significantly greater in the Ag plus-118 dB noise group
      relative to the Ag-alone group or 118 dB noise-exposure group. ICAM expression
      was seen in the lower part of the spiral ligament and small vessels within the
      normal cochlea. The amount of expression increased after Ag injection and
      acoustic trauma. Activated nuclear transcription factor-kappaB occurred in the
      nuclei of hair cells, supporting cells, spiral ligament fibrocytes, and neurons 4
      hours after noise exposure. CONCLUSIONS: It seems that noise exposure can
      activate a cochlear immune response, which in the presence of Ag, allows for
      greater recruitment of inflammatory cells than occurred in response to Ag alone.

PMID- 18806478
TI  - Radiofrequency ablation for the treatment of obstructive sleep apnea: a meta
      analysis.
AB  - OBJECTIVES/HYPOTHESIS: Recent studies suggest that radiofrequency ablation (RFA)
      is a treatment option for patients with obstructive sleep apnea (OSA). This study
      investigates the effectiveness of RFA in treating OSA using a critical literature
      review and meta-analysis. STUDY DESIGN: Critical literature review and meta
      analysis. METHODS: Two independent searches of PubMed 1966-present were performed
      to identify publications pertaining to RFA and OSA. Effectiveness of the
      procedure was measured by comparing the Epworth Sleepiness Scale (ESS),
      respiratory disturbance index (RDI), and lowest O2 saturation before and after
      tissue ablation. RESULTS: Sixteen studies met the inclusion criteria. The study
      found a 31% reduction in short-term ESS (odds ratios (OR) 0.69, 95% confidence
      interval (CI) 0.63-0.75), which was maintained beyond 12 months (OR 0.68, 95% CI
      0.43-0.73). Likewise, RFA resulted in a 31% reduction in short term (<12 month)
      (OR 0.69, 95% CI 0.61-0.77) and 45% reduction (OR 0.55, 95% C.I. 0.45-0.72) in
      long-term (>24 month) RDI levels. Short-term results of the lowest O2 saturations
      failed to demonstrate improvement (OR 1.03, 95% CI 0.88-1.20). CONCLUSION: RFA
      seems to be a clinically effective tool that reduces ESS scores and RDI levels in
      patients with OSA syndrome. The procedure should be considered a valid treatment
      option for patients who refuse or are unable to tolerate continuous positive
      airway pressure.

PMID- 18806479
TI  - The need for standardization of methods for worldwide infant hearing screening: a
      systematic review.
AB  - No uniform case definition presently exists for infant hearing screening programs
      worldwide especially for minimal hearing loss (HL). This article systematically
      reviewed the current practices in developing countries for programs aimed at
      early detection of "disabling" congenital and early-onset HL and found
      significant variations which undermine comparability of key findings in the
      reported studies. Implications for the exclusion of minimal HL are explored
      within the context of the International Classification of Functioning, Disability
      and Health (ICF) of the World Health Organization and its adapted version for
      children and youth (ICF-CY). A revised World Health Organization classification
      that accounts for all categories of HL based on ICF-CY may provide a suitable
      framework for improved uniformity in reporting standards.

PMID- 18806480
TI  - Dependence of hearing changes on the dose of intratympanically applied
      gentamicin: a meta-analysis using mathematical simulations of clinical drug
      delivery protocols.
AB  - OBJECTIVES/HYPOTHESIS: To establish safe dosing protocols for the treatment of
      patients with Meniere's disease with intratympanic gentamicin. STUDY DESIGN: A
      validated computer model of gentamicin dispersion in the inner ear fluids was
      used to calculate cochlear drug levels resulting from specific clinical delivery
      protocols. Dosing in the cochlea was compared with changes of hearing sensitivity
      for 568 patients reported in 19 publications. METHODS: Cochlear drug levels were
      calculated based on the concentration and volume of gentamicin applied, the time
      the drug remained in the middle ear, and on the specific timing of injections.
      Time courses were quantified in terms of the maximum concentration (Cmax) and the
      area under the curve of the drug at specific cochlear locations. RESULTS: Drug
      levels resulting from single, "one-shot" injections were typically lower than
      those from repeated or continuous application protocols. Comparison of hearing
      sensitivity changes with gentamicin dosing revealed a flat curve with a near-zero
      mean for lower doses, suggesting that hearing changes with doses over this range
      were probably unrelated to the applied drug. Higher intracochlear doses were
      generated with repeated or continuous delivery protocols, which in some cases
      caused substantial hearing losses and an increased incidence of deafened ears.
      CONCLUSIONS: One-shot application protocols produce gentamicin doses in the
      cochlea that have minimal risk to hearing at the frequencies tested. Repeated or
      continuous application protocols result in higher doses that in some cases damage
      hearing. The high variability of hearing changes, even with low gentamicin doses,
      calls into question the rationale for using individual hearing changes to titrate
      the applied dose.

PMID- 18806481
TI  - Cutaneous and superficial soft tissue lesions associated with Albright hereditary
      osteodystrophy: clinicopathological and molecular genetic study of 4 cases,
      including a novel mutation of the GNAS gene.
AB  - Albright hereditary osteodystrophy is a rare syndrome, in which cutaneous and
      superficial soft tissue lesions traditionally include osteomas and
      calcifications. We report 4 patients from 2 families affected with Albright
      hereditary osteodystrophy and demonstrate that the spectrum of these cutaneous
      and soft tissue lesions is broader than is usually defined in the literature. In
      addition to osteomas in the dermis and subcutis, including so-called plaque-like
      osteoma, we identified the following lesions: calcifying aponeurotic fibroma-like
      lesion, calcinosis circumscripta-like lesion, and unusual nevi with osteoid
      and/or peculiar intranuclear pseudoinclusions. One osteoma and the calcifying
      aponeurotic fibroma-like lesion were analyzed by HUMARA and proved to be clonal.
      In a family, a novel mutation in the GNAS gene was also identified.

PMID- 18806482
TI  - Evaluation of B-cell clonality using the BIOMED-2 PCR method effectively
      distinguishes cutaneous B-cell lymphoma from benign lymphoid infiltrates.
AB  - Primary cutaneous B-cell lymphomas (CBCL) are a diverse group of lymphomas that
      are limited to the skin at the time of diagnosis. Recently, standardized
      polymerase chain reaction protocols for immunoglobulin (Ig) rearrangement in
      nodal malignancies using the BIOMED-2 method have been studied extensively.
      However, reports of investigations of Ig clonality in CBCL using the BIOMED-2
      method have been scant. We hypothesized that clonality detection in CBCL with the
      BIOMED-2 method could effectively distinguish malignant from benign B-cell-rich
      infiltrates in the skin. Formalin-fixed tissue samples from 26 patients with CBCL
      and 23 with benign lymphoid infiltrates were analyzed for Ig clonality using
      standardized BIOMED-2 polymerase chain reaction protocols. The (14;18)
      translocation was also assessed. A clone was detected in 22 (85%) of the 26
      patients with CBCL [12/15 (80%) marginal zone B-cell lymphoma; 10/11 (91%)
      follicle center lymphoma] and in 1 (4%) of the 23 patients with benign
      infiltrates. The (14;18) translocation was present in 3 (12%) of the 26 patients
      with CBCL [1/15 (7%) marginal zone B-cell lymphoma; 2/11 (18%) follicle center
      lymphoma]. Our preliminary data indicate that Ig clonality can be detected in
      formalin-fixed samples of CBCL with meaningful sensitivity (85%) and high
      specificity (96%) using the BIOMED-2 method. This study forms the basis for
      further investigating the role of Ig clonality in distinguishing CBCL from benign
      lymphoid infiltrates that may pose a challenge in morphologic diagnosis.

PMID- 18806483
TI  - Superficial acral fibromyxoma: report of 4 cases with CD10 expression and
      lipomatous component, two previously underrecognized features.
AB  - Superficial acral fibromyxoma (SAF) is an uncommon tumor of the superficial soft
      tissues of acral extremities in middle-aged adults, firstly described in a series
      of 37 cases by Fetsch et al. in 2001. Since then, just a few case reports have
      been published. It is histologically characterized by a slightly to moderately
      cellular proliferation of spindled and stellate-shaped bland fibroblastic cells,
      arranged in a random, loose storiform, or fascicular growth pattern, within a
      myxoid, myxocollagenous, or collagenous stroma, with a prominent vasculature. The
      cells express CD34, CD99, and, frequently, epithelial membrane antigen. We report
      4 cases that show clinical, morphological, and immunohistochemical
      characteristics of SAF and, additionally, exhibit two features rarely documented
      in previous publications, such as CD10 expression and a lipomatous component.
      Three of our 4 cases express CD10. The single previously reported case tested for
      CD10 was also positive. One of our cases contains mature fat cells intermingled
      with the spindle cells throughout the lesion. This finding has not been
      documented before in SAF. Our small series shows that SAF frequently expresses
      CD10 and occasionally can have a lipomatous component.

PMID- 18806484
TI  - Spiradenoma and spiradenocylindroma with an adenomatous or atypical adenomatous
      component: a clinicopathological study of 6 cases.
AB  - We report 5 cases of spiradenoma and 1 case of spiradenocylindroma, which, in
      addition to areas of conventional growth, manifested an adenomatous component.
      This consisted of compactly situated, well-developed glands having small round
      lumens lined by inner pale to eosinophilic cells and surrounded by an outer well
      formed peripheral layer of myoepithelial cells, which reacted with a variety of
      myoepithelial cell markers. In 1 case, apocrine secretion was evident in the
      glandular part of the lesion. In 4 of the 6 cases, the adenomatous component was
      a minor but significant portion of the tumors, but in 2 cases it was extensive,
      comprising approximately 20% of the tumor area. In 1 of these 2 cases, the
      luminal epithelium showed atypia including rare, atypical mitotic figures. In
      addition, there were foci of glands showing myoepithelial cell loss. As this
      alteration was limited and fairly well circumscribed within the tumor bulk, we
      regard it as an "atypical adenomatous component," but we cannot exclude the
      possibility that this may represent an incipient apocrine carcinoma, despite
      uneventful follow-up. Three cases also manifested clear cell areas.
      Immunohistochemical studies demonstrated that myoepithelial proliferation and
      overgrowth accounted for the clear cell change in some of the lesions.

PMID- 18806485
TI  - Vascular density has prognostic value in Merkel cell carcinoma.
AB  - Merkel cell carcinomas are aggressive tumours for which histological prognostic
      factors need to be established. This study examines the prognostic role of
      vascular density, based on CD34 immunohistochemical staining in Merkel cell
      carcinoma. Thirty-six cases of Merkel cell carcinoma were immunohistochemically
      stained for the endothelial marker CD34. Vascular density was assessed in the
      tumor and stroma with a Chalkley eyepiece graticule. The scores of vascular
      density were correlated with other clinical and histological parameters to
      determine the prognostic significance of tumor vascularity. Increased vascular
      density was shown to be significantly associated with a worse prognosis (P =
      0.005). A 1-unit increase in total vessel score was associated with a 3.9 times
      increase in the risk of death (95% hazard ratio confidence limits 1.50-10.32).
      Other factors associated with a worse outcome included tumor size (P = 0.05), the
      presence of lymphovascular invasion (P = 0.03), and tumor mast cell count (P <
      0.002). Increased vascular density is associated with a worse prognosis in Merkel
      cell carcinomas. Assessment of vascular density may assist in predicting clinical
      behavior in these tumors and in evaluating the effects of adjuvant therapy.

PMID- 18806486
TI  - State of the art of teledermatopathology.
AB  - Teledermatopathology may involve real-time transmission of images from distant
      locations to consulting pathologists by the remote manipulation of a robotic
      microscope. Alternatively, the static store-and-forward option involves the
      single-file transmission of subjectively preselected and captured areas of
      microscopic images by a referring physician. The recent introduction of virtual
      slide systems (VSS) involves the digitization of whole slides at high resolution
      thus enabling the user to view any part of the specimen at any magnification.
      Such technology has surmounted previous restrictions caused by the size of
      preselected areas and specimen sampling for telepathology. In terms of client
      access, these VSS may be stored on a virtual slide server, made available on the
      Web for remote consultation by pathologists via an integrated virtual slide
      client network. Despite store-and-forward teledermatopathology being the most
      frequently used and less expensive approach to teledermatopathology, VSS
      represents the future in this discipline. The recent pilot studies suggest that
      the use of remote expert consultants in diagnostic dermatopathology can be
      integrated into daily routine, teleconsultation, and teleteaching. The new
      technology enables rapid and reproducible diagnoses, but despite its usability,
      VSS is not completely feasible for teledermatopathology of inflammatory skin
      diseases as the performance seems to be influenced by the availability of
      complete clinical data. Improvements in the diagnostic facility will no doubt
      follow from further development of the VSS, the slide processor, and of course
      training in the use of virtual microscope. Undoubtedly, as technology becomes
      even more sophisticated in the future, VSS will overcome the present drawbacks
      and find its place in all facets of teledermatopathology.

PMID- 18806487
TI  - Vitiligo-like primary melanoma.
AB  - Depigmented or hypopigmented macules and patches have been described in
      association to primary and metastatic melanoma. Primary melanoma presenting at
      the onset as a vitiliginous patch without histopathological evidence of
      regression seems to be a rare event. We report 2 patients with melanoma in situ
      that expressed clinically as vitiligo-like patches and review the possible
      immunologic mechanisms responsible for this unusual presentation.

PMID- 18806488
TI  - Bullous mastocytosis: report of a patient and a brief review of the literature.
AB  - We report a 6-month-old male infant who presented to the pediatric dermatology
      clinic at Wake Forest University Baptist Medical Center with a generalized
      bullous eruption since 3 months of age. A sepsis work up was performed at an
      outside hospital before presentation and did not reveal any evidence of systemic
      infection. Clinical presentation revealed a well-nourished, appropriate-for-age,
      6-month-old boy with multiple tense bullae, some in a "string of pearls"
      arrangement, on the bilateral upper extremities and trunk. Multiple erosions were
      also noted. Laboratory evaluation revealed a normal complete blood count.
      Polymerase chain reaction was negative for herpes simplex virus types I and II.
      Histologic sections demonstrated a large space of separation between the
      epidermis and dermis which was filled by a monomorphous infiltrate composed of
      round to oval cells with centrally placed nuclei, consistent with mast cells.
      Leder and C-Kit stains were strongly positive, confirming the diagnosis of
      bullous mastocytosis. Treatment included fluocinonide 0.05% cream and tacrolimus
      0.1% ointment to active lesions and silver sulfadiazine 1% cream to erosions.
      Improvement was noted during follow-up examination.

PMID- 18806489
TI  - Merkel cell carcinoma in situ arising in a trichilemmal cyst: a case report and
      literature review.
AB  - A 73-year-old man presented with a 4-mm asymptomatic, smooth, dome-shaped lesion
      on the right fourth finger with a clinical impression of a cyst/dermatofibroma.
      Histological examination showed a trichilemmal cyst with 3 nests of small blue
      round cells within the basal layer of the cyst lining. There were many mitotic
      figures and apoptotic bodies. The stain for cytokeratin 20 "decorated" the tumor
      cells with an unequivocal perinuclear dot-like pattern, confirming their Merkel
      cell origin. Dermal Merkel cell carcinoma (MCC) arising in association with
      benign adnexal tumors or cysts, with or without epithelial involvement, is a rare
      event. MCC in situ in this context has not been previously reported. The
      immunostain for cytokeratin 20 is an important ancillary study in diagnosing MCC.
      Our case supports the view that a subset of MCCs is of intraepithelial origin and
      underscores the clinical importance of surveillance for changes in an "innocent"
      cyst.

PMID- 18806490
TI  - An unusual case of granulomatous slack skin disease with necrobiosis.
AB  - Granulomatous slack skin disease (GSS) is a very rare form of T-cell lymphoma,
      with only 52 cases reported in the literature. In the recent World Health
      Organization-European Organization for Research and Treatment of Cancer consensus
      classification GSS is considered to be a variant of mycosis fungoides. We
      describe a patient with GSS and histologic evidence of necrobiosis, which has not
      been previously reported.

PMID- 18806491
TI  - Oral lichenoid lesions in HIV-HCV-coinfected subjects during antiviral therapy: 2
      cases and review of the literature.
AB  - Some dental materials and certain drugs may induce epithelial alterations, which
      clinically resemble oral lichen planus (OLP), on oral mucosa. But these
      alterations do not have all the clinical and/or the histological features of OLP;
      these lesions are known as oral lichenoid lesions (OLLs). Some researchers
      describe the onset and/or the worsening of OLL/OLP after the administration of
      anti-hepatitis C virus (HCV) therapy. In this article, we describe the
      development of symptomatic OLLs, as a consequence of anti-HCV therapy (interferon
      alpha and ribavirine), in 2 human immunodeficiency virus-HCV-coinfected subjects.
      An immunological cause related to coinfection and administration of different
      medications could be responsible for the onset of OLLs. These new cases, together
      with the previous reports of a possible association between OLP and/or OLL and
      anti-HCV therapy, highlight the absolute need to monitor carefully the human
      immunodeficiency virus-HCV-coinfected subjects who are about to start the anti
      HCV therapy and to define better the clinical and histopathological criteria to
      distinguish OLP from OLL.

PMID- 18806492
TI  - Spiradenocylindroma-like basaloid carcinoma of the anus and rectum: case report,
      including HPV studies and analysis of the CYLD gene mutations.
AB  - The authors report a case of basaloid carcinoma involving the anus and rectum of
      a 57-year-old woman. Microscopically, the tumor showed unusual morphologic
      features strongly resembling a spiradenocylindroma because it consisted, in most
      parts, of basaloid cell nodules arranged in a jigsaw-puzzle fashion containing or
      surrounded by eosinophilic basal membrane material; in addition, there were
      intratumoral lymphocytes. The overlying squamous epithelium manifested dysplastic
      changes compatible with in situ squamous carcinoma that gradually became invasive
      and blended with basaloid cell islands; additionally, there were koilocytes in
      the squamous epithelium. A molecular biology study identified HPV-16 in the
      lesional tissue. Analysis of the CYLD gene did not prove any mutation.

PMID- 18806493
TI  - Immunohistochemical investigation of mid-dermal elastolysis with a history of
      erythema.
AB  - Elastic fibers are essential extracellular matrix macromolecules comprising an
      elastin core surrounded by fibrillin-rich microfibrils. Fibulin-5, a microfibril,
      has been identified as one of the secreted extracellular matrix proteins that
      shows function as a scaffold for elastic fibers. However, the distribution of
      fibulin-5 in the skin is not clear. We report a case of a 43-year-old woman with
      erythema and subsequent wrinkling that met the clinical and histological criteria
      for mid-dermal elastolysis. We investigate the mechanism by which this disease
      occurs. The distribution of elastin, CD68, matrix metalloproteinase (MMP)-9, and
      fibulin-5 was examined immunohistochemically from both erythematous and wrinkled
      skin. There were numerous CD68 and MMP-9-producing histiocytes and giant cells in
      the erythematous lesions. Faint fibrillar staining of fibulin-5 was found in the
      deep dermis. In the wrinkled skin, there were few CD68 histiocytes or giant
      cells. Elastin immunoreactivity disappeared from the mid-dermis. Fibulin-5
      colocalized in the lower dermis, shorter than in the erythema. Mid-dermal
      elastolysis may be initiated by MMP-9 produced by histiocytes and giant cells
      through its degradation of elastic fibers. In the lower dermis of the wrinkled
      skin, the fragmented expression of fibulin-5 was associated with the incomplete
      reproduction of the elastic fibers.

PMID- 18806494
TI  - An unusual case of coccidioidomycosis presenting with skin lesions.
AB  - A 42-year-old white male without prior skin disease presented 8 months ago with
      chest pain, fever, and coughing to his primary physician. At that point, he had
      no skin lesions. The diagnosis was made by standard blood tests. The patient
      completed treatment and was symptom free for 8 months until he presented to his
      physician again with skin lesions on his right cheek and extremities. The patient
      was referred to our dermatology clinic for further evaluation. A complete skin
      examination revealed lesions on his face, extremities, and back. The lesions on
      his right face were 8 x 10-mm erythematous papules and nodules coalescing into a
      plaque. A biopsy was taken from his right cheek lesions.

PMID- 18806495
TI  - CD34+ pigmented fibrous proliferations: the morphologic overlap between pigmented
      dermatofibromas and Bednar tumors.
AB  - Pigmented dermatofibrosarcoma protuberans (DFSP; Bednar tumor) constitutes 5%-10%
      of all cases of DFSP and shows morphologic features that overlap with melanocytic
      and fibrous proliferations. We report 2 unusual cases of pigmented fibrous
      proliferations that demonstrate features of dermatofibromas and DFSP. The first
      case is that of a 19-year-old man with a 3-year history of a slowly growing
      pigmented lesion on the right arm. On clinical exam, the lesion was a 7-mm firm
      pigmented papulonodular lesion. The second case is that of a 31-year-old woman
      with a 4- to 5-year history of a slowly enlarging, asymptomatic "dark area" on
      the right buttock. On clinical exam, the lesion was a 2-cm darkly pigmented flat
      nodule. Morphologically, both lesions are primarily dermal proliferations of
      spindled cells admixed with pigmented dendritic melanocytes. The lesional cells
      trap collagen fibers at the periphery and there is basal cell hyperpigmentation.
      Adnexal structures are effaced, but significant trapping of subcutaneous fat is
      not present. By immunohistochemistry, both lesions show focal CD34 positivity but
      are negative for Factor XIIIa and melanocytic markers. Although overlap between
      standard dermatofibromas and DFSP is well documented in the literature, pigmented
      fibrous lesions with features of both entities are not well described.

PMID- 18806496
TI  - Rhabdomyomatous mesenchymal hamartoma with lentiginous melanocytic hyperplasia:
      an inductive phenomenon or component of the hamartoma?
AB  - Rhabdomyomatous mesenchymal hamartoma (RMH) is a rare cutaneous hamartoma
      characterized by abundant bundles of mature skeletal muscle fibers admixed with
      other mesenchymal elements. We report a case of RMH in a 7-month-old girl with
      associated lentiginous melanocytic hyperplasia. The melanocytic hyperplasia was
      not apparent clinically and was only evident on histological examination. Unlike
      a smooth muscle hamartoma, melanocytic abnormalities have never been described in
      the context of RMH. Though the exact significance of this observation is not
      clear, we speculate that the melanocytic hyperplasia could be related to an
      inductive phenomenon or constitute a part of the overall hamartomatous process.
      Careful attention to epidermal changes in future cases of RMH may help in
      understanding the significance of this association and refine our knowledge of
      the pathogenesis of RMH.

PMID- 18806497
TI  - Cutaneous toxoplasmosis histologically mimicking graft-versus-host disease.
AB  - The dermatology service is frequently consulted to assess cutaneous eruptions
      after hematopoietic stem cell transplantation. We describe a case of cutaneous
      toxoplasmosis in a stem cell transplant patient where toxoplasmosis trophozoites
      elicited a reaction pattern mimicking an interface dermatitis. At first blush,
      these findings may be misinterpreted as either a reaction to a drug or graft
      versus-host disease. We hope that this case will prove helpful for
      dermatopathologists in asserting the correct diagnosis of cutaneous toxoplasmosis
      if left untreated or treated incorrectly, this disease has a dismal prognosis.

PMID- 18806498
TI  - Is there a cutaneous variant of marginal zone hyperplasia?

PMID- 18806499
TI  - Langerhans cell histiocytosis mimicking malignant melanoma: a diagnostic pitfall.
AB  - Langerhans cell histiocytosis (LCH), especially with an involvement limited to
      the skin, is a rare entity in adults. In formulating a differential diagnosis of
      a solitary skin lesion, LCH is rarely considered. Morphologically, cells seen in
      LCH can mimic those seen in a melanocytic tumor; moreover, they both show S-100
      protein reactivity with immunoperoxidase staining. A 63-year-old male presented
      to a dermatology clinic with a solitary hyperpigmented macule on his right calf.
      A biopsy specimen showed epithelioid cells within the dermis, singly and in small
      groups, surrounded and infiltrated by collections of histiocytes and lymphocytes.
      These cells were diffusely positive for S-100 and negative for Melan-A. A
      diagnosis of malignant melanoma, spitzoid variant, was rendered, and the patient
      was sent to our melanoma center for surgical treatment. On histologic
      examination, some of the lesional cells had reniform, vesicular nuclei with
      central grooves. Additional immunoperoxidase staining showed strong, diffuse
      positivity for CD1a, supporting the diagnosis of LCH. LCH is morphologically
      similar to and can be misdiagnosed as malignant melanoma. It is important to be
      aware of this pitfall and utilize immunohistochemical and ultrastructural
      analysis to achieve correct diagnosis.

PMID- 18806500
TI  - Giant, congenital folliculosebaceous cystic hamartoma: a case against a
      pathogenetic relationship with trichofolliculoma.
AB  - Folliculosebaceous cystic hamartoma (FSCH) is a rare cutaneous hamartoma
      consisting of dilated folliculosebaceous units invested in mesenchymal elements.
      These solitary lesions typically affect adults, have a predilection for the
      central face or scalp, and remain less than 1.5 cm in greatest dimension.
      Although giant FSCH variants have been documented, the congenital presentation of
      a giant FSCH stands in contrast to earlier views of its histogenetic relationship
      with trichofolliculoma. We describe a giant pedunculated FSCH arising from the
      posterior neck of a 9-month-old Hispanic male and discuss various aspects of this
      highly unusual case.

PMID- 18806501
TI  - Mucinous carcinoma of the skin: evaluation of lymphatic invasion with D2-40.
AB  - Primary cutaneous mucinous carcinoma is a rare adnexal sweat gland neoplasm that
      mainly affects elderly people. Differential diagnosis includes mammary and
      gastrointestinal metastatic mucinous carcinoma (MC) and secondary cutaneous
      involvement by underlying neoplasms. An 83-year-old woman presented with an 8
      year history of slow-growing infiltrate plaque in her right hemithorax, with
      ulceration on supraclavicular area, right upper limb edema and palpable axillary
      lymphadenopathies. She underwent partial excision of the tumor and local
      radiotherapy. Imaging studies showed widespread cutaneous dissemination with
      enlargement of ipsilateral axillary lymph nodes but without evidence of
      underlying breast cancer. Histopathological examination showed large amounts of
      mucin in the dermis including small islands of epithelial cells. They stained
      positive for cytokeratin 7, carcinoembryonic antigen, epithelial membrane
      antigen, gross cystic disease fluid protein-15, and c-erbB-2. Lymphatic invasion
      was demonstrated by D2-40-immunostained sections. A diagnosis of primary
      cutaneous mucinous carcinoma was made. Our aim was to reevaluate the differential
      clinical, histopathological, and immunohistochemical criteria for distinguishing
      primary cutaneous mucinous carcinoma from skin metastases of visceral mucinous
      carcinoma, especially those arising in breast. We also propose D2-40 as a
      reliable marker to detect lymphatic invasion that indicates a strong aggressive
      trend with shorter recurrence-free and predicts nodal metastases.

PMID- 18806502
TI  - Sebocyte-like melanocytes in desmoplastic blue nevus.

PMID- 18806503
TI  - Ashy dermatosis with significant perivascular and subepidermal fibrosis.

PMID- 18806504
TI  - Primary mucinous carcinoma of the skin: usefulness of p63 in excluding metastasis
      and first report of psammoma bodies.

PMID- 18806505
TI  - Unilateral eyelid discoid lupus erythematosus.

PMID- 18806506
TI  - Mechanical arm trainer for the treatment of the severely affected arm after a
      stroke: a single-blinded randomized trial in two centers.
AB  - OBJECTIVE: To test whether training with a new mechanical arm trainer leads to
      better outcomes than electrical stimulation of the paretic wrist extensors in
      subacute stroke patients with severe upper limb paresis. Electrical stimulation
      is a standard and reimbursable form of therapy in Germany. DESIGN: Randomized
      controlled trial of 54 inpatients enrolled 4-8 wks from stroke onset, mean upper
      extremity subsection of Fugl-Meyer assessment (0-66) at admission less than 18.
      In addition to standard care, all patients practiced 20-30 mins arm trainer or
      electrical stimulation every workday for 6 wks, totaling 30 sessions. Primary
      outcome was the Fugl-Meyer assessment, secondary outcomes were the Box and Block
      test, the Medical Research Council and the modified Ashworth scale, blindly
      assessed at enrollment, after 6 wks, and at 3-mo follow-up. RESULTS: Both groups
      were homogeneous at study onset. Shoulder pain occurred in two arm trainer
      patients. The primary Fugl-Meyer assessment outcome improved for both groups over
      time (P < 0.001), but this improvement did not differ between groups. The initial
      (terminal) mean Fugl-Meyer assessment scores were 8.8 +/- 4.8 (19.2 +/- 14.5) for
      the arm trainer and 8.6 +/- 3.5 (13.6 +/- 7.9) for the electrical stimulation
      group. No patient could transport a block initially, but at completion
      significantly more arm trainer patients were able to transport at least three
      blocks (five vs. zero, P = 0.023). No significant differences were observed
      between the groups on the secondary Box and Block outcome at follow-up (eight vs.
      four patients). All Box and Block responders had an initial Fugl-Meyer assessment
      > or =10. CONCLUSIONS: Arm trainer training did not lead to a superior primary
      outcome over electrical stimulation training. However, "good performers" on the
      secondary outcome seemed to benefit more from the arm trainer training.

PMID- 18806507
TI  - Magnetic resonance imaging vs. electrodiagnostic root compromise in lumbar spinal
      stenosis: a masked controlled study.
AB  - OBJECTIVE: The high false-positive rate of magnetic resonance imaging (MRI) makes
      it a less-than-reliable tool for evaluating clinically significant stenosis.
      Finding MRI changes that correlate with electrodiagnostic abnormalities might
      lead to more successful treatment decision making. The purpose of this study was
      to identify MRI changes that correlate with neurologic abnormalities measured by
      electrodiagnosis in patients with spinal stenosis. DESIGN: One hundred fifty
      persons with and without back pain between the ages of 55 and 79 yrs participated
      in this prospective, blinded, controlled study. Exclusion criteria included
      previous spine surgery or known neuropathy. Needle electromyography of the limb,
      nerve conduction studies, including peroneal F-wave and tibial H-wave, and
      noncontrast lumbo-sacral spine MRI were completed. A codified physical medicine
      and rehabilitation history and physical examination was completed to
      differentiate symptomatic lumbar stenosis patients from asymptomatic controls.
      The relationship between lumbar MRI measurements and extremity electromyography
      findings was studied. RESULTS: MRI measurements did not differ significantly with
      respect to extremity needle electromyography findings in the entire population or
      in patients with clinical signs of lumbar stenosis. In the entire population, an
      absent tibial H-wave corresponded to the interfacet ligament distance at L5-S1
      and anterior to posterior canal size at L4-5. In patients clinically evaluated as
      having lumbar stenosis, peroneal F-wave latency correlated with anteroposterior
      canal size at L4-5 and interfacet ligament and anterior to posterior lateral
      recess narrowing at L5-S1. In patients with clinical signs and symptoms of lumbar
      stenosis, limb electromyography findings did not correlate with MRI measurements,
      although H-wave and F-wave testing correlated with relevant locations of
      stenosis. CONCLUSIONS: Needle electromyography does not differentiate patients
      with symptomatic mild or moderate lumbar stenosis. However, H-wave and F-wave
      correlated to specific anatomical changes on MRI in this patient population.

PMID- 18806508
TI  - The clinical value of B-type natriuretic peptide (BNP) in predicting nocturnal
      low back pain in patients with concurrent lumbar spinal stenosis and
      cardiopulmonary dysfunction (Vesper's Curse): a clinical case series.
AB  - OBJECTIVE: To test the hypothesis that B-type natriuretic peptide is elevated in
      patients with both lumbar spinal stenosis and cardiopulmonary dysfunction who
      reported sleep-interrupting low back pain, the "symptomatic group," as compared
      with an analogous cohort not experiencing nocturnal low back pain, i.e., the
      "control group." B-type natriuretic peptide is a hormonal product of the
      myocardium, which increases with an elevation in blood volume. Even without
      clinical symptoms, the more the myocardial stretch, the higher the B-type
      natriuretic peptide. DESIGN: In both groups, all of the patients were identified
      as having lumbar spinal stenosis and a history of cardiopulmonary dysfunction.
      However, all of the symptomatic group reported initially falling asleep and then
      experiencing sleep interrupting low back pain. However, in both groups, their
      cardiac status remained clinically stable. Main outcome measures included both
      the B-type natriuretic peptide titer and lumbar spinal magnetic resonance
      imaging. RESULTS: There were 10 patients with nocturnal pain and eight who were
      pain-free at night. The magnetic resonance imaging in both cohorts demonstrated a
      spectrum of moderate to severe lumbar spinal stenosis. Their previous cardiac
      history varied from the presence of arrhythmias to that of congestive heart
      failure. Other risk factors including age, among others, were similar in both
      cohorts. The mean B-type natriuretic peptide titer in the control group was 67.88
      +/- 46.58 pg/ml. In the symptomatic group it was significantly elevated to 136.90
      +/- 62.14 pg/ml. CONCLUSIONS: In this clinical care series, the B-type
      natriuretic peptide titer was significantly increased in the symptomatic group as
      compared with the control group. The standard error of the mean was 19.65 in this
      group and 16.47 in the control group. An elevated B-type natriuretic peptide
      reflects a decrement in cardiac efficiency which may not be clinically evident.
      It also has a profound hypotensive effect because of its diuretic, natriuretic,
      and vascular dilatory properties. As a direct consequence of the increased right
      heart filling pressure, retrograde engorgement of the paravertebral plexus of
      veins surrounding the spinal neural elements may occur. Dilation of these
      valveless veins within an already stenotic spinal canal may induce the symptoms
      of Vesper's Curse, i.e., sleep-disrupting lumbar pain as a symptom of spinal
      stenosis in patients with a history of cardiopulmonary disease.

PMID- 18806509
TI  - A preliminary study on the impact of pushrim-activated power-assist wheelchairs
      among individuals with tetraplegia.
AB  - OBJECTIVES: This preliminary study was to evaluate the impact of pushrim-
      activated power-assist wheelchairs (PAPAWs) on mobility, community participation,
      satisfaction, and psychosocial impact among individuals with tetraplegia. DESIGN:
      Fifteen manual wheelchair users with tetraplegia completed a 4-wk protocol
      including a 2-wk trial where they used their personal wheelchairs for mobility
      and a 2-wk trial where they were provided with a PAPAW and could choose either
      wheelchair for mobility. The mobility levels with both wheelchairs were recorded
      by a datalogger. Participants completed daily questionnaires regarding community
      participation and their satisfaction with the wheelchair used. The Psychosocial
      Impact of Assistive Devices Scale was used to compare the psychosocial impact of
      PAPAWs with their personal wheelchairs. RESULTS: Participants chose to use PAPAWs
      and their personal wheelchairs at a similar frequency in the PAPAW trial. The
      distances traveled with both wheelchairs were not statistically different (P =
      0.09). Participants traveled significantly faster with PAPAWs (P = 0.03). PAPAWs
      did not result in significantly greater community participation, satisfaction,
      and psychosocial impacts than the personal wheelchairs. CONCLUSIONS: PAPAWs could
      be a viable mobility option for individuals with tetraplegia, which can provide
      independent mobility especially for outdoor activities. A user's preference, life
      style, physical conditions, transportation issues, and environmental factors
      should be considered in prescribing such a device.

PMID- 18806510
TI  - Subjective Quality-of-Life Predictors for Older Adults with Physical
      Disabilities.
AB  - OBJECTIVES: To study changes in quality of life (QOL) and to explore predictors
      of QOL of community-dwelling older adults with physical disabilities. DESIGN: A 2
      yr longitudinal study involved a convenience sample of 49 people with physical
      disabilities aged 60-94 yrs. QOL was estimated twice at a 2-yr interval with the
      Quality of Life Index, which includes four domains: health and functioning,
      socioeconomic, psychological/spiritual, and family. The potential predictors
      evaluated at baseline were health condition, activity, participation (level and
      satisfaction), personal factors, and environmental factors (obstacles and
      facilitators). RESULTS: No change over time in QOL mean score was observed (mean:
      -0.41; SD: 2.5; 95% confidence interval: -1.1 to 0.30; P = 0.25). However, about
      half the participants had a clinically significant change (either increase or
      decrease). Greater satisfaction with participation in social roles and fewer
      obstacles in the physical environment were identified as the best predictors (R2
      = 0.27; P = 0.001) of better QOL. Greater participation in daily activities,
      fewer obstacles in the physical environment, and greater satisfaction with
      participation in social roles were found to be the best predictors (R2 = 0.49; P
      < 0.001) of high health and functioning QOL. Finally, increased QOL score over
      the 2-yr period was best predicted by initial lower socioeconomic QOL and
      activity level perceived as unstable (R2 = 0.27; P = 0.001). CONCLUSIONS: QOL is
      partially explained by participation and environmental factors. These factors may
      be positively modified and thus may warrant special attention in health
      interventions. Identified predictors of QOL changes over time need to be
      considered in intervention studies.

PMID- 18806511
TI  - Adaptive short forms for outpatient rehabilitation outcome assessment.
AB  - OBJECTIVE: To develop outpatient Adaptive Short Forms for the Activity Measure
      for Post-Acute Care item bank for use in outpatient therapy settings. DESIGN: A
      convenience sample of 11,809 adults with spine, lower limb, upper limb, and
      miscellaneous orthopedic impairments who received outpatient rehabilitation in 1
      of 127 outpatient rehabilitation clinics in the United States. We identified
      optimal items for use in developing outpatient Adaptive Short Forms based on the
      Basic Mobility and Daily Activities domains of the Activity Measure for Post
      Acute Care item bank. Patient scores were derived from the Activity Measure for
      Post-Acute Care computerized adaptive testing program. Items were selected for
      inclusion on the Adaptive Short Forms based on functional content, range of item
      coverage, measurement precision, item exposure rate, and data collection burden.
      RESULTS: Two outpatient Adaptive Short Forms were developed: (1) an 18-item Basic
      Mobility Adaptive Short Form and (2) a 15-item Daily Activities Adaptive Short
      Form, derived from the same item bank used to develop the Activity Measure for
      Post-Acute Care computerized adaptive testing program. Both Adaptive Short Forms
      achieved acceptable psychometric properties. CONCLUSIONS: In outpatient postacute
      care settings where computerized adaptive testing outcome applications are
      currently not feasible, item response theory-derived Adaptive Short Forms provide
      the efficient capability to monitor patients' functional outcomes. The
      development of Adaptive Short Form functional outcome instruments linked by a
      common, calibrated item bank has the potential to create a bridge to outcome
      monitoring across postacute care settings and can facilitate the eventual
      transformation from Adaptive Short Forms to computerized adaptive testing
      applications easier and more acceptable to the rehabilitation community.

PMID- 18806512
TI  - Zoster sine herpete with thoracic motor paralysis temporally associated with
      thoracic epidural steroid injection.
AB  - Reactivation of latent varicella-zoster virus can occur when the immune system is
      weakened leading to the typical presentation seen with herpes zoster or shingles.
      In a small percentage of these patients, motor paralysis can be seen in the
      affected myotomal distribution. Zoster sine herpete, or shingles without the
      typical vesicular rash, is an uncommon variant of zoster. Systemic steroids are
      known to weaken the immune response. Two previous case reports have implicated
      epidural steroid injections as a precipitating cause of zoster. We present a case
      of serologically verified zoster sine herpete producing an abdominal wall bulge,
      which occurred 1 wk after thoracic epidural steroid injection. Electromyography
      documented the presence of abdominal wall denervation. Given the low incidence of
      serologically proven zoster sine herpete--especially with thoracic motor
      paralysis--and the equally rarely documented incidence of zoster related to
      epidural steroids, we present what we believe to be the first reported case of
      zoster sine herpete with a neuropathic abdominal wall bulge occurring in close
      temporal association to receiving epidural steroids.

PMID- 18806513
TI  - Axillary mononeuropathy after herpes zoster infection mimicking subacromial
      impingement syndrome.
AB  - Subacromial impingement syndrome is a frequent cause of shoulder pain and it is
      readily confused with other shoulder problems. We present a patient with herpes
      zoster infection associated with axillary mononeuropathy that was initially
      misdiagnosed as subacromial impingement syndrome. A 75-yr-old female patient was
      admitted to the internal medicine clinic because of pain and weakness in her
      right shoulder. As she did not respond to medical treatment and local injection
      therapy, magnetic resonance imaging of the right shoulder was ordered. As the
      magnetic resonance imaging revealed subacromial impingement of the supraspinatus
      tendon, the patient was referred to the physical medicine and rehabilitation
      department for rehabilitation. In our initial physical examination, her shoulder
      abductor muscle strength was 2/5 and her shoulder external rotator muscle
      strength was 3/5. A subacromial injection test with 10 ml of 1% lidocain was
      negative and the magnetic resonance imaging did not show a complete rotator
      tendon rupture that could explain such a muscle strength loss. So, an
      electrodiagnostic evaluation was performed and the patient was diagnosed to have
      a right axillary neuropathy. A more detailed questioning of the patient disclosed
      a history of herpes zoster approximately 3 mos ago. Herpes zoster-associated
      axillary neuropathy can mimic subacromial impingement syndrome, and magnetic
      resonance imaging examination alone may lead to a misdiagnosis. Therefore, we
      imply that clinical and electrophysiological evaluations would be of great
      importance in relevant patients with shoulder problems.

PMID- 18806514
TI  - Electrodiagnosis as an extension of the physical examination: identifying
      proximal median neuropathy in the setting of carpal tunnel syndrome.

PMID- 18806515
TI  - Licensing to prescribe.

PMID- 18806516
TI  - Effect of chloroquine on the urinary excretion of ciprofloxacin.
AB  - Ciprofloxacin is an inexpensive antibacterial, whereas chloroquine is an
      inexpensive antimalarial. The coadministration of chloroquine and ciprofloxacin
      is easily encountered because both drugs are commonly prescribed to patients in
      the tropics. Five healthy male volunteers aged 19 to 31 years who were not taking
      any of the prescribed medications and who had no sensitivity to either
      ciprofloxacin or chloroquine each received 500 mg ciprofloxacin orally with 250
      mL of water, and after a 2-week washout period, 500 mg ciprofloxacin plus 600 mg
      chloroquine was administered orally with 250 mL of water after providing informed
      consent. A urine sample (7 mL) was collected just before taking the drug at 8:00
      AM representing 0 hour and continued afterward at 1, 2, 4, 8, 12, and 24 hours
      the next day. The samples were stored at -20 degrees C until analyzed. The
      minimum inhibitory concentrations by diffusion through agar technique were used
      for the assay of urine ciprofloxacin. The rate of ciprofloxacin excretion and
      cumulative urine ciprofloxacin were significantly increased. The coadministration
      of chloroquine increased the cumulative urinary concentration and excretion rate
      of ciprofloxacin.

PMID- 18806517
TI  - Current management of anemia in critically ill patients: analysis of a database
      of 139 hospitals.
AB  - PURPOSE: This analysis focused on three objectives: 1) to measure packed red
      blood cell (pRBC) use across different critical care settings; 2) to characterize
      transfused and nontransfused critically ill patients; and (3) to identify
      potential predictors of transfusion use. METHODS: A retrospective analysis of
      critically ill patients from 139 hospitals across the United States was
      conducted. Hospital administrative and laboratory data were collected for
      patients 18 years of age and older admitted to the intensive care unit (ICU)
      (including coronary care unit and intermediate care units) from January 1, 2004,
      to May 31, 2005. Multivariate analyses controlling for patient and hospital
      heterogeneity evaluated the association between pRBC transfusions and patients'
      ICU or hospital length of stay. RESULTS: A total of 180,221 patients met all
      inclusion criteria, with 29,331 (16.3%) receiving pRBCs during their ICU stay.
      There was differential use of pRBCs by ICU/coronary care unit setting (ie, 23% of
      general ICU patients versus 7% of intermediate coronary care unit patients).
      Increasing age [odds ratio (OR), 1.007; 95% confidence interval (CI), 1.006
      1.008], declining hemoglobin concentrations (OR, 2.315; 95% CI, 2.288-2.342),
      mechanical ventilation (OR, 1.338; 95% CI, 1.287-1.392), dialysis (OR, 2.071; 95%
      CI, 1.913-2.242), and presence of acute renal failure (OR, 1.259; 95% CI, 1.193
      1.329), congestive heart failure (OR, 1.156; 95% CI, 1.106-1.208), or septicemia
      (OR, 1.143; 95% CI, 1.071-1.221) were associated with a higher likelihood of pRBC
      use. Each pRBC transfusion significantly increased hospital length of stay (1.6,
      0.5, and 2.7 additional days for patients with 1, 2, and 3 or more transfusions,
      respectively, P < 0.0001) as compared with nontransfused patients. CONCLUSIONS:
      Multiple factors increased the likelihood of pRBC use in ICU patients. In
      addition, pRBC transfusion was associated with increased length of stay.
      Clinicians should evaluate the risk-benefit ratio and consider interventions to
      limit any unnecessary pRBC use in the critically ill.

PMID- 18806518
TI  - Effect of caffeine on myocardial perfusion imaging using single photon emission
      computed tomography during adenosine pharmacologic stress.
AB  - Approximately 6 million cardiac stress tests are performed annually in the United
      States, of which 2.4 million are pharmacologic stress tests using agents such as
      adenosine. Adenosine induces differential coronary hyperemia in normal coronary
      arteries versus coronary arteries with atherosclerosis, allowing single photon
      emission computed tomography (SPECT) imaging to identify reduced coronary flow in
      segments subtended by diseased coronary arteries. The potential attenuation of
      pharmacologic effects of adenosine in the presence of caffeine is why patients
      are routinely instructed to abstain from caffeine for 12 to 24 hours prior to
      administration of an adenosine stress test. Failure to abstain from caffeine
      results in cancellation or delaying of cardiac stress testing, resulting in
      procedural delays and its impact on patient throughput. Recent studies have
      evaluated such interaction and suggested a lack of clinically significant effect
      of caffeine on adenosine-induced hyperemia during myocardial SPECT imaging. This
      article reviews the clinical pharmacology of caffeine, adenosine, and
      dipyridamole and effect of caffeine on myocardial stress testing using adenosine
      and dipyridamole in clinical cardiovascular medicine. The limited published data
      are conflicting, but some recent publications suggest that myocardial perfusion
      SPECT imaging using adenosine may not be clinically significantly altered by
      routine consumption of caffeine, such as a cup of coffee. Although prospective
      randomized studies would be required to obtain a definitive answer to this
      question, it appears on the basis of some of the studies reviewed in this article
      that caffeine consumption prior to myocardial perfusion imaging may not
      necessitate cancellation or rescheduling of adenosine stress testing.

PMID- 18806519
TI  - Pathogen safety of intravenous Rh immunoglobulin liquid and other immune globulin
      products: enhanced nanofiltration and manufacturing process overview.
AB  - Plasma products for therapeutic use pose specific challenges in manufacturing to
      ensure products maintain biologic activity and are safe with respect to
      contamination and transmission of disease-causing agents. Various processes have
      demonstrated effectiveness in eliminating, reducing, or inactivating viral
      contaminants. Recently, the possibility of transmitting variant Creutzfeld-Jakob
      disease (vCJD) or transmissible spongiform encephalopathies (TSE) through blood
      based products has become a concern. The present study involves the validation of
      a hyperimmune immunoglobulin manufacturing process incorporating a nanofiltration
      step with a nominal pore size of 20 nm for removal of viral contaminants and
      other adventitious agents. Processing intermediates during the manufacture of IV
      Rh IgG (WinRho SDF/WinRho SDF Liquid, Cangene Corporation, Manitoba, Canada) were
      spiked with model viruses and processed in scaled-down procedures to validate the
      viral reduction capacity of each step. Anion-exchange chromatography and
      solvent/detergent steps are known to contribute to virus removal and
      inactivation. The Planova 20 N nanofiltration step was effective in reducing
      model viruses representing a wide range of viral morphologies with varying
      degrees of resistance to physicochemical inactivation. All in-process and final
      batch testing met current standards for production of IV Rh IgG manufactured with
      the previously licensed filter, which had a larger nominal pore size of 35 nm.
      The manufacturing process, employing a Planova 35 N filtration step, has been
      proactively improved by the change to a smaller-pore 20 N filter. Replacement of
      the 35 N filter with the 20 N filter produces a similar product while enhancing
      the capability for removal of smaller viruses and prions.

PMID- 18806520
TI  - Use of gastroprotection in patients discharged from hospital on nonsteroidal anti
      inflammatory drugs.
AB  - BACKGROUND: Gastrointestinal (GI) hemorrhage is responsible for 200-400,000
      hospitalizations in the United States annually. Nonsteroidal anti-inflammatory
      drugs (NSAIDs) are responsible for > or =30% of admissions due to GI hemorrhage.
      Misoprostol reduces the number of NSAID-related upper GI events while proton pump
      inhibitors (PPIs) reduce the incidence of endoscopic ulcers. AIMS: To measure the
      utilization of GI prophylaxis in patients discharged from hospital on ulcerogenic
      medicines. PATIENTS AND METHODS: We performed a medical record review of all 480
      patients discharged from the medical service over a 3-month period on aspirin or
      nonaspirin NSAIDs. Use of gastroprotection was recorded, particularly among those
      patients not previously prescribed a PPI or misoprostol. Patients with a
      different indication for PPI therapy were excluded. RESULTS: In all, 480 patients
      were identified, and 142 were excluded. Of the 338 remaining patients, 154 (46%)
      were prescribed GI prophylaxis. In particular, 240 patients had not been
      receiving a PPI or misoprostol at the time of admission (gastroprotection naive).
      Of these, 23.3% received a new prescription for GI prophylaxis at discharge. Use
      of gastroprotection increased among patients older than 60 years compared with
      those 60 years and younger (P = 0.008), but there was no difference among
      patients with higher baseline comorbidity or those receiving multiple agents of
      interest. CONCLUSIONS: Although hospitalization offers an opportunity to
      recognize patients at high risk of developing upper GI complications from NSAIDs,
      utilization of appropriate gastroprotection seemed suboptimal. Educational
      efforts directed at physicians may help them recognize risk factors for GI
      hemorrhage and current indications for prophylaxis.

PMID- 18806521
TI  - Assessing the impact of protocol design changes on clinical trial performance.
AB  - Although it is widely acknowledged that protocol design plays a crucial role in
      the success of clinical research studies, how protocols have changed over time
      and the impact of these changes on clinical trial performance have never been
      quantified. To measure protocol design trends, the Tufts Center for the Study of
      Drug Development analyzed data on 10,038 unique phase 1-4 protocols conducted
      between 1999 and 2005. Tufts Center for the Study of Drug Development analyzed
      study conduct performance data on 57 individual phase 2 and 3 protocols
      administered at US-based investigative sites. The results of this study indicate
      that the number of unique procedures and the frequency of procedures per protocol
      have increased at the annual rate of 6.5% and 8.7%, respectively, during the time
      period measured. Investigative site work burden to administer each protocol
      increased at an even faster rate of 10.5% between 1999 and 2005. Additionally,
      during this time period, study conduct performance--that is, cycle time and
      patient recruitment and retention rates--worsened; and the number of protocol
      amendments, observed serious adverse events, and length of case report forms
      increased substantially. Implications of these results for simplifying protocol
      designs and minimizing negative effects on study conduct performance are
      discussed.

PMID- 18806522
TI  - Prevalence of use of cardiovascular drugs in 499 patients with suspected coronary
      artery disease at time of hospitalization for coronary angiography and in 357
      patients with obstructive coronary artery disease documented by coronary
      angiography.
AB  - In a prospective study of 499 patients with suspected coronary artery disease
      (CAD) hospitalized for coronary angiography, the prevalence of use of
      cardiovascular drugs at hospital admission was 80% for antiplatelet drugs, 66%
      for beta blockers, 55% for angiotensin-converting enzyme (ACE) inhibitors or
      angiotensin receptor blockers (ARBs), 65% for lipid-lowering drugs, 24% for
      calcium channel blockers (CCBs), and 16% for nitrates. In 357 patients with
      obstructive CAD diagnosed by coronary angiography, the prevalence of use of these
      drugs at hospital discharge was 100% for antiplatelet drugs, 97% for beta
      blockers, 91% for ACE inhibitors or ARBs, 98% for lipid-lowering drugs, 17% for
      CCBs, and 27% for nitrates. Obstructive CAD was significantly more prevalent in
      men (P < 0.025), in cigarette smokers (P < 0.01), and in patients with
      hypertension, diabetes, or hypercholesterolemia (P < 0.001). Age, race, body mass
      index, and neck circumference were not significantly different for patients with
      versus without obstructive CAD.

PMID- 18806523
TI  - Characterization of the heart rate-lowering action of ivabradine, a selective
      I(f) current inhibitor.
AB  - Ivabradine is a heart rate-lowering agent devoid of other direct cardiovascular
      effects that has been approved for treatment of patients with stable angina
      pectoris. The heart rate-lowering action of ivabradine, and its relation to
      clinical effects, was characterized during its development program in clinical
      and preclinical studies. Ivabradine selectively inhibits If in sinoatrial node
      cells, reducing diastolic depolarization rate and heart rate. At therapeutic
      concentrations, ivabradine has no action on other cardiac or vascular ion
      channels or receptors. Heart rate reduction with ivabradine is dose dependent and
      tends to a maximum or plateau level at high doses. With repeated oral dosing, the
      heart rate-lowering effect of ivabradine is near maximal in 2 weeks, maximal
      within 4 weeks, and is maintained without development of pharmacological
      tolerance during long-term treatment. On cessation of treatment, heart rate
      returns rapidly and progressively to pretreatment levels without rebound
      tachycardia or untoward cardiovascular events. In patients with stable angina,
      the reduction in heart rate is greatest in patients with the highest pretreatment
      heart rate, a property that should minimize the potential for ivabradine to
      produce excessive bradycardia. Heart rate lowering with ivabradine is associated
      with increases in indices of heart rate variability and causes no more than
      minimal changes in blood pressure. The characteristics of the heart rate-lowering
      action of ivabradine make it suitable for a range of patients including those for
      whom other antianginal agents may be contraindicated or not acceptably tolerated.
      They also suggest that management of treatment should be relatively simple in
      most patients.

PMID- 18806524
TI  - Cardiovascular effects of psychotropic drugs.
AB  - BACKGROUND: Cardiovascular disease is the leading cause of death in the general
      population and accounts for approximately 30% of all deaths; some of these are
      due to fatal arrhythmias, especially ventricular fibrillation. In a psychiatric
      population the prevalence of cardiovascular disease is higher than in the general
      population because of a different lifestyle and greater frequency of risks
      factors such as smoking, obesity, and increased stress. The increased prevalence
      of sudden death in this patient population has given rise to the question of drug
      induced cardiovascular and arrhythmic effects. This article reviews the principal
      classes of psychotropic medications and their effects on the heart. METHODS: The
      review is based on Medline, Pubmed, Cochrane, and literature searches of
      publications from the period 1984 to 2005. CONCLUSION: It is important for
      practitioners to be familiar with the possible effects of psychotropic
      medications on the cardiovascular system, especially in the elderly and other
      patients with preexisting cardiac problems. Before starting treatment with a new
      psychotropic medication, a careful history and physical are mandatory, and
      baseline liver, lipid, and kidney profiles as well as chest radiographic and
      electrocardiographic findings should be noted.

PMID- 18806525
TI  - Therapeutic potential of dipeptidyl peptidase-IV inhibitors in patients with
      diabetes mellitus.
AB  - Dipeptidyl peptidase-IV (DPP-IV) inhibitors are a new class of oral antidiabetic
      agents for the treatment of patients with type 2 diabetes. Inhibition of the
      enzyme DPP-IV results in increased activity of glucagon-like peptide-1 (GLP-1)
      and glucose-dependent insulinotropic peptide (GIP), the incretin hormones.
      Through the action of GLP-1 and GIP, DPP-IV inhibitors improve preprandial and
      postprandial glucose by enhancing insulin secretion and reducing postprandial
      concentrations of glucagon. This review examines the background, current
      evidence, and future therapeutic potential of this novel class of drug.

PMID- 18806526
TI  - Antipsychotic-induced hyponatremia: case report and literature review.
AB  - We report a case of hyponatremia in a patient that occurred 3 days after
      initiation of treatment with aripiprazole. The patient was a 50-year-old man
      admitted to an inpatient psychiatric unit for exacerbation of schizophrenia. He
      was started on aripiprazole and developed hyponatremia that resolved when the
      medication was stopped. We postulate that the hyponatremia was due to an
      aripiprazole-induced syndrome of inappropriate secretion of antidiuretic hormone.
      There have been numerous case reports in the literature of hyponatremia in the
      literature associated with atypical antipsychotics. We caution clinicians to be
      aware that the potential hyponatremic-inducing effects of atypical antipsychotics
      can occur rapidly after initiation of the medications.

PMID- 18806527
TI  - The identification of benefit in medical intervention: an overview and
      suggestions for process.
AB  - Benefit and risk assessments are not only important to regulatory authorities but
      also important to the providers, patients, pharmaceutical industry, and payers.
      In order for patients and providers to continue to have access to new innovative
      medicines, which have some level of inherent risk, it is critical to have a
      systematic and balanced focus on understanding the safety risks and benefits to
      the patient during drug development, at the time of approval and postmarketing.
      There has been a significant amount of activity around efforts to improve the
      ability to assess risks in the postmarketing environment. However, there is no
      widely accepted, systematic approach or process for the ongoing evaluation of
      benefit. This article introduces 4 critical components in the process of
      identifying and assessing benefit with a goal of providing a framework that is
      transparent, comprehensive, applicable to various perspectives, and simple to
      communicate and implement. We propose the development of a catalog applied to a
      particular disease to identify the optimal data sources and methods to address
      the interests of a given perspective. Two key resources will need to be developed
      to support the catalog development: (1) a summary of benefit measures and
      preferences by disease and from various perspectives and (2) an investment in a
      simple visual communication mechanism with minimal statistical language. As the
      emphasis is on transparency, relevance, applicability, and communication, this
      approach to assessing benefit should maximize the impact of these data to all
      stakeholders and decision makers.

PMID- 18806528
TI  - Introduction to the special issue on pain in couples.

PMID- 18806529
TI  - Examination of perceived spouse responses to patient well and pain behavior in
      patients with headache.
AB  - OBJECTIVES: Primary: to examine the association between perceived spouse
      responses to patient well behaviors and important patient variables (pain
      behavior, pain intensity, pain interference, and depressive symptoms). Secondary:
      to examine whether perceived spouse responses to patient pain behaviors are
      associated with important pain-related variables. METHODS: Sixty-four patients
      with headache and their spouses completed self-report questionnaire packets that
      included measures of pain intensity, pain behaviors, depression, marital
      satisfaction, and perceived spouse responses to pain and well behaviors. Separate
      regression models were used to predict each dependent variable. RESULTS: Patient
      reports of spouse negative responses to well behaviors were significantly
      associated with greater patient reported pain behavior and pain intensity,
      whereas perceptions of facilitative responses to well behaviors were not
      significantly related to any dependent variable. Patient reports of spouse
      solicitous responses to patient pain behaviors were associated with higher levels
      of pain behavior, depressive symptoms, pain intensity, and pain interference.
      DISCUSSION: Perceptions of spouse responses to patient well behaviors seem to
      have important associations with patient functioning, yet have received
      insufficient research attention. The Spouse Response Inventory (SRI) thus
      represents a valuable addition to available research instruments because it
      assesses spouse responses to well behaviors.

PMID- 18806530
TI  - Pain communication in the context of osteoarthritis: patient and partner self
      efficacy for pain communication and holding back from discussion of pain and
      arthritis-related concerns.
AB  - OBJECTIVES: This preliminary study examined aspects of pain communication (self
      efficacy for pain communication and holding back from discussing pain and
      arthritis-related concerns) among patients with osteoarthritis (OA) and their
      partners, and associations between patient and partner pain communication and
      measures of patient and partner adjustment. METHODS: A sample of 38 patients with
      OA and their partners completed measures of self-efficacy for pain communication
      and holding back from discussion of pain and arthritis-related concerns. Patients
      completed measures of pain, physical and psychologic disability, and pain
      catastrophizing, and partners completed measures of caregiver strain and positive
      and negative affect. RESULTS: Correlation analyses indicated that, among
      patients, higher levels of self-efficacy for pain communication were associated
      with significantly lower levels of pain, physical and psychologic disability, and
      pain catastrophizing, and with lower levels of partner negative affect. Among
      partners, high self-efficacy for pain communication was associated with higher
      levels of positive affect. Among patients, higher levels of holding back were
      significantly correlated with higher levels of psychologic disability and
      catastrophizing. Higher levels of partner holding back were associated with
      significantly higher levels of caregiver strain, and with higher levels of
      patient psychologic disability and catastrophizing. DISCUSSION: Taken together,
      results from this preliminary study suggest that self-efficacy for pain
      communication and holding back from discussions of pain and arthritis-related
      concerns may be important in understanding how patients with OA and their
      partners adjust to the demands of the patient's disease.

PMID- 18806531
TI  - Individual and relational correlates of pain-related empathic accuracy in spouses
      of chronic pain patients.
AB  - OBJECTIVE: This study aims to investigate correlates of pain-related empathic
      accuracy in spouses of chronic pain patients. Specifically, analyses addressed:
      (1) the correlates of pain-related empathic accuracy, (2) the relation between
      pain-related empathic accuracy, and patient and spouse adaptational outcomes, and
      (3) the relation between pain-related empathic accuracy and relational outcomes.
      METHODS: Fifty-eight chronic pain patients (28 women and 30 men) were filmed
      while participating in a simulated occupational lifting task. Patients were asked
      to report their level of pain while lifting canisters partially filled with sand.
      Spouses were later asked to view the video record of their partner's performance
      and to estimate their partner's level of pain. Empathic accuracy was defined in
      terms of the overall discrepancy between patients' pain ratings and spouses' pain
      estimates, and by the degree of covariation between patients' pain ratings and
      spouses' pain estimates across trials. RESULTS: Analysis revealed that patients'
      pain severity, catastrophizing, fear of pain, and level of disability were
      significant correlates of empathic accuracy. Higher levels of pain-related
      empathic accuracy were associated to negative adaptational outcomes for chronic
      pain patients. With regard to the spouse, empathic accuracy was associated with
      the spouses' perceiving that they express less punitive responses when the
      patient is in pain. Empathic accuracy was not significantly related to relational
      outcomes. DISCUSSION: The results of this study suggest that empathic accuracy is
      associated with negative outcomes for the patient, and might not be an important
      correlate of marital satisfaction in couples in which one of the partners is
      suffering from chronic pain.

PMID- 18806532
TI  - Empathic and nonempathic interaction in chronic pain couples.
AB  - OBJECTIVES: Empathy and empathic response are receiving greater attention in pain
      research as investigators acknowledge that other forms of interaction may impact
      the pain process. The purpose of this study was to examine validation and
      invalidation as forms of empathic and nonempathic responses in chronic pain
      couples. METHODS: Participants were 92 couples in which at least one spouse
      reported chronic musculoskeletal pain. Each couple participated in 2 videotaped
      interactions about the ways in which the pain has impacted their lives together.
      Trained raters then coded interactions for each partner's use of validation and
      invalidation. Couples also completed surveys on spouse responses to pain, marital
      satisfaction, and perceived spousal support. RESULTS: Correlations demonstrated
      validation by spouses of persons with pain was associated with punishing,
      solicitous, and distracting spouse responses to pain, marital satisfaction, and
      perceived spousal support. In contrast, spouses' invalidation scores were
      correlated with punishing spouse responses. Exploratory factor analyses were then
      conducted to determine the extent to which spouses' responses to pain and spouse
      validation and invalidation loaded on similar factors. Validation and
      invalidation are more closely related to punishing spouse responses than to
      solicitous or distracting spouse responses. DISCUSSION: This work suggests that
      empathic and nonempathic communication are distinct from solicitous spouse
      responses. The findings have implications for theoretical and clinical work on
      social factors in pain.

PMID- 18806533
TI  - An open-label pilot trial of ibandronate for complex regional pain syndrome.
AB  - OBJECTIVE: Complex regional pain syndrome (CRPS) type I, also known as reflex
      sympathetic dystrophy, usually develops after trauma or immobilization, is
      characterized by focal pain and autonomic dysregulation, and sometimes focal
      trophic changes such as osteoporosis. The pathophysiology is unknown and there
      have been few controlled treatment trials. The purpose of this study was to
      obtain pilot data on the safety and efficacy of a highly potent bisphosphonate,
      ibandronate, for the treatment of CRPS, which might be responsive to
      bisphosphonates' inhibition of osteoclast and anti-inflammatory activity.
      METHODS: An open-label trial (n=10) of 6 mg ibandronate infusions was
      administered on each of 3 days. The infusions were preceded by a 2-week baseline
      period, and followed by a 4-week follow-up period. RESULTS: One participant
      dropped out after the first infusion because of a decreased glomerular filtration
      rate. Otherwise, aside from transitory flu-like symptoms characteristic of
      bisphosphonate treatments, the drug was well tolerated. Significant
      postintervention improvements were observed in average and worst pain ratings;
      the neuropathic pain qualities of "unpleasant," "sensitive," "deep," "intense,"
      "surface," "hot," "cold," "sharp," and "dull"; and hyperalgesia and allodynia.
      Participants with hand CRPS improved significantly more than those with foot CRPS
      in average and worst pain, as well as in the following neuropathic pain
      qualities: "dull," "intense," "deep," and "time." DISCUSSION: These data justify
      a randomized, double-blind, placebo-controlled trial of ibandronate that should
      perhaps be limited to patients with hand CRPS.

PMID- 18806534
TI  - Topical fentanyl in a randomized, double-blind study in patients with corneal
      damage.
AB  - OBJECTIVES: Corneal damage causes severe pain. This study investigated whether
      peripheral opioid receptors are present in the human cornea and assessed the
      efficacy of topical fentanyl in patients with corneal erosion. METHODS:
      Immunohistochemical staining experiments were performed to examine the presence
      of both mu and delta-receptors on peripheral nerve fibers within human corneal
      tissue. In a randomized, double-blind clinical trial dexpanthenol (n=20) or
      dexpanthenol plus 10 microg fentanyl (n=20) were topically applied every 4 hours
      to the eye of patients with a surgical intervention of corneal damage and
      subjective pain intensity was determined by a numerical rating scale. RESULTS:
      Immunohistochemical staining identified peripheral nerve fibers in human cornea
      expressing both mu and delta-opioid receptors. In patients with corneal damage
      the ophthalmic intervention in local anesthesia decreased the subjective pain
      intensity significantly. At 4-hour intervals after the ophthalmic intervention,
      moderate pain intensity levels were not altered by the application of
      dexpanthenol with or without fentanyl. At 24 hours pain intensity dropped
      significantly, most likely owing to a natural decrease in pain, because the
      erosion was almost healed. DISCUSSION: Both mu and delta-receptors are localized
      on nerve fibers within the cornea, which are accessible for topical opioid
      treatment. However, our formulation and dose of topical fentanyl in combination
      with dexpanthenol did not show any benefit in relieving pain from corneal
      erosion. Future studies are planned to determine the optimal protocol and dose of
      topical opioid treatment.

PMID- 18806535
TI  - Pain assessment as intervention: a study of older adults with severe dementia.
AB  - OBJECTIVES: The communication impairments that characterize severe dementia make
      pain assessment challenging. As such, pain problems often go undetected. Our goal
      was to determine whether systematic pain assessment leads to improved pain
      management practices and decreases nursing stress in comparison with a control
      condition. METHODS: We adopted a 3-month comparative longitudinal design. Nursing
      staff regularly assessed dementia patients' pain through the use of the Pain
      Assessment Checklist for Seniors with Limited Ability to Communicate (PACSLAC). A
      second group of nurses completed an attention-control measure for a control group
      of patients. In addition, nursing staff regularly completed measures of work
      stress to investigate the effects of the workload associated with systematic pain
      assessment on nurse stress. RESULTS: Regular use of the PACSLAC improved pain
      management practices over time as reflected in increased usage of analgesic
      medications (prescribed on "as needed" basis) in comparison with the control
      group. As pain interventions increased, a corresponding decrease in observable
      pain behaviors (as reflected on the PACSLAC assessments that were completed by
      the nurses) was observed. In addition, nurses who used the PACSLAC reported
      decreased distress and burnout over time. DISCUSSION: This investigation provides
      strong support for both the importance of systematic pain assessment in long-term
      care and for the clinical utility of the PACSLAC in improving pain management
      practices and decreasing caregiver distress.

PMID- 18806536
TI  - Clinical and demographic characteristics of patients with chronic pain after
      major thoracotomy.
AB  - OBJECTIVES: The characteristics and etiology of long-term pain after major
      thoracotomy and methods for its prevention have yet to be established. METHODS:
      One hundred and twenty patients who had completed the hospital-based portion of a
      prior study to evaluate the efficacy of intraoperative epidural use during major
      thoracotomy, all of whom had received patient-controlled thoracic epidural
      analgesia until at least thoracostomy tube removal, and who were followed for 48
      weeks after surgery provided data for this study. RESULTS: Although preoperative
      pain was associated with elevated pain levels during hospitalization and the
      first few months after discharge, there was no association with pain 48 weeks
      after surgery. Furthermore, pain during the first few postoperative days,
      although associated with pain during the first few postoperative months, was not
      associated with pain 48 weeks after surgery. However, for patients who reported
      pain 48 weeks after surgery, pain levels were elevated late in hospitalization
      after epidural catheter removal and pain after discharge did not decrease over
      time. During hospitalization, patients who would eventually report pain 48 weeks
      after surgery experienced a greater impact of pain and reported that analgesic
      therapy was less effective. DISCUSSION: Postoperative pain that persists but
      eventually dissipates was a common finding whose intensity was associated with
      immediate preoperative and postoperative pain levels. In contrast, pain later on
      during hospitalization, its impact, and perceived analgesic effectiveness best
      identified those who would continue to report pain almost 1 year after surgery.

PMID- 18806537
TI  - A comparison of the neuroablative effects of conventional and pulsed
      radiofrequency techniques.
AB  - OBJECTIVES: To compare the neuroablative effects of pulsed radiofrequency (PRF)
      and conventional radiofrequency (CRF) techniques on the sciatic nerve, a
      peripheral nerve that includes motor, sensory, and autonomous fibers. METHODS:
      The study consisted of 5 groups of 6 adult male Wistar rats. In the control
      group, no procedure was performed. In the sham group, electrode placement was the
      same as the other groups, but radiofrequency energy was not given to the rats. In
      the CRF40 group, 40 degrees C CRF was applied to the rats for 90 seconds. In the
      CRF80 group, 80 degrees C CRF was applied for 90 seconds. In the PRF group, the
      rats received 45 V PRF, which did not exceed 42 degrees C for 240 seconds. Two
      days later, sciatic nerve samples were taken. All specimens were evaluated both
      with light and electron microscopy. Sciatic nerve morphology was analyzed to
      compare the effects of CRF and PRF. Kruskal-Wallis and Mann-Whitney U tests were
      used for comparing the means. RESULTS: Minimal damage was observed in the control
      group, but damage increased in the sham group and became increasingly more
      distinct in the PRF, CRF40, and CRF80 groups. DISCUSSION: Nerve tissues can be
      affected during any type of procedure, even during surgical applications. Our
      results suggest that PRF is less destructive than CRF for the peripheral nerves.
      However, this idea should also be investigated at the molecular level, and safety
      analysis should be performed for routine clinical practice.

PMID- 18806538
TI  - Higher internality of health locus of control is associated with the use of
      complementary and alternative medicine providers among patients seeking care for
      acute low-back pain.
AB  - OBJECTIVES: Given that persons with a stronger belief in internal health locus of
      control (HLC) have been shown to comply well with medical advice, HLC internality
      may play an important role in low-back pain (LBP) prevention and management
      because it requires the patient's own commitment. Previous studies in conditions
      other than LBP have shown that the use of complementary and alternative medicine
      (CAM) is associated with high HLC internality. Here, we examined the relationship
      between CAM facility visits and internality of HLC in persons with LBP. METHODS:
      We analyzed the data from the Health Diary Study, which surveyed the health
      related behavior of 3477 persons sampled from the general population of Japan.
      Among 2377 participants aged 18 to 75 years, 673 reported LBP during the study
      period. We examined CAM facility visits and HLC among 81 previously untreated LBP
      patients who sought care from western medical doctors or CAM providers during the
      1-month study period. RESULTS: Of the 81 patients, 40 reported at least 1 CAM
      visit, whereas 41 visited western medical doctors only. Participants who visited
      CAM facilities had a higher internality score than those who visited western
      medical doctors after controlling for age, sex, size of residential city, and
      bodily pain score of the Short Form-8 Health Survey scale. DISCUSSION: Visitors
      to CAM facilities had a stronger belief in internal HLC. This finding suggests
      that visitors to CAM facilities are more sensitive to educational intervention
      for the self-management of LBP than those who visit western medicine. In order
      not to miss the opportunity of reaching these patients, the education should be
      more emphasized on CAM facilities.

PMID- 18806539
TI  - Complementary therapies for neuropathic and neuralgic pain: systematic review.
AB  - OBJECTIVE: To assess the evidence from rigorous clinical trials, systematic
      reviews, and meta-analyses of complementary and alternative therapies for
      treating neuropathic and neuralgic pain. METHODS: Systematic searches were
      carried out in the databases Medline, Embase, Amed, Scopus, the Cochrane Database
      of Systematic Reviews, Natural Standard, and the Natural Medicines Comprehensive
      Database. Each database was searched from its respective inception until March
      2006. To be included, trials were required to state that they were randomized.
      Systematic reviews and meta-analyses were included if based on the results of
      randomized trials. No language restrictions were imposed. RESULTS: Five relevant
      systematic reviews and meta-analyses and 15 additional trials met the inclusion
      criteria and were reviewed. Data on the following complementary and alternative
      medicine treatments were identified: acupuncture, electrostimulation, herbal
      medicine, magnets, dietary supplements, imagery, and spiritual healing.
      CONCLUSIONS: On the basis of our findings, the evidence is not fully convincing
      for most complementary and alternative medicine modalities in relieving
      neuropathic or neuralgic pain. However, for topically applied capsaicin there is
      evidence of effectiveness beyond placebo. The evidence can be classified as
      encouraging and warrants further study for cannabis extract, magnets, carnitine,
      and electrostimulation.

PMID- 18806540
TI  - Pemphigus pain: a review on management.
AB  - Pemphigus vulgaris is an autoimmune disease that commonly presents with painful
      persistent erosions and ulcers. OBJECTIVE: The current literature has focused on
      managing and maintaining remittance of this life-threatening disease. However,
      remission is not instantaneous and chronic pain is common. In this manuscript, we
      review the current peer reviewed works that elaborate specifically on pain
      management in pemphigus patients. METHODS: A medline search was preformed and
      included any case report, review, clinical trial, or other publication that
      covered the subject matter. RESULTS: From the review of literature, it is clear
      that pain is an important and underemphasized part of the literature on
      pemphigus. The majority of pain management in these patients is based on clinical
      experience rather than randomized blinded clinical studies. DISCUSSION: Large
      scale blinded randomized studies are lacking in this field, and would be of great
      benefit to academia and the patient population. Current large-scale studies of
      pemphigus would also be strongly enhanced by inclusion and reporting pain scale
      assessments.

PMID- 18806541
TI  - Pulsed radiofrequency treatment of lower extremity phantom limb pain.
AB  - BACKGROUND: Phantom limb pain can be challenging to treat. We present a patient
      who developed severe phantom limb pain after revision of her lower extremity
      amputation due to the continued progression of peripheral vascular disease.
      Multiple treatment modalities had been tried without success. Pulsed
      radiofrequency has been successfully used to manage a number of pain syndromes.
      OBJECTIVE: The present case report describes the use of pulsed radiofrequency
      treatment for phantom limb pain. METHODS: The authors initially preformed
      regional blocks of femoral and sciatic nerve with 0.375% bupivicaine 15 cc and 50
      microg clonidine to control the patient's pain. The blocks provided good pain
      relief but with limited duration. Based on reports of prolonged pain relief
      provided by pulsed radiofrequency treatment for other chronic pain conditions
      such as lumbrosacral spondylosis, we decided to apply this treatment to the
      patient's sciatic nerve. The patient underwent pulsed radiofrequency treatment
      with 2 cycles of 120 seconds at 42 degrees, pulse rate of 2 pulse/second, and
      pulse duration of 20 milliseconds. RESULTS: Our report shows that the sciatic
      nerve block with bupivicaine and clonidine, initiated approximately 3 years after
      amputation, produced modest short-term relief. The pulsed radiofrequency
      treatment resulted in long-term relief of phantom limb pain. The patient was able
      to wean herself off all oral medications and has been pain free for 4 months.

PMID- 18806542
TI  - Exercise-associated hyponatremia: why are athletes still dying?

PMID- 18806543
TI  - Exercise-associated hyponatremia masquerading as acute mountain sickness: are we
      missing the diagnosis?

PMID- 18806544
TI  - Twelve-month outcomes of serious orthopaedic sport and active recreation-related
      injuries admitted to Level 1 trauma centers in Melbourne, Australia.
AB  - OBJECTIVE: To describe and identify predictors of 12-month outcomes of serious
      orthopaedic injuries due to sport and active recreation. DESIGN: Prospective
      cohort study with 12-month follow-up. SETTING: Two Level 1 adult trauma centers
      in Victoria, Australia. PARTICIPANTS: A total of 366 adults admitted to two Level
      1 trauma centers for an orthopaedic sport and active recreation injury between
      August 2003 and March 2006. Patients were captured by the Victorian Orthopaedic
      Trauma Outcomes Registry (VOTOR), followed up at 12 months, and were free of
      moderate to severe disability prior to injury. ASSESSMENT OF RISK FACTORS:
      Independent variables assessed for predictors of outcome were sporting group,
      age, sex, marital status, education level, Injury Severity Score, injury
      patterns, and head injury status. MAIN OUTCOME MEASUREMENTS: The 12-item Short
      Form Health Survey and maximum pain scores. RESULTS: At 12 months postinjury,
      22.8% of patients reported moderate to severe physical disability, 12.1% reported
      moderate to severe mental health disability, and 11.1% reported moderate to
      severe pain. There were significant differences in physical outcomes between
      sporting groups, with motor and equestrian sports reporting the worst physical
      outcomes. Multivariate analysis indentified increasing age (P = 0.010) and
      patterns of injury (P = 0.040) as significant predictors of a poor physical
      outcome at 12 months. No significant independent predictors of outcome for mental
      health and maximum pain at 12 months were identified. CONCLUSION: Almost one
      quarter of participants reported moderate to severe physical disability at 12
      months postinjury. Increasing age and patterns of injury were found to be
      significant predictors of a poor physical outcome at 12 months.

PMID- 18806545
TI  - Effect of ice hockey helmet fit on cervical spine motion during an emergency log
      roll procedure.
AB  - OBJECTIVE: To investigate cervical spine motion during a log roll technique in
      ice hockey players under different helmet fit conditions. DESIGN: Prospective
      counterbalanced design. SETTING: University research laboratory. PARTICIPANTS:
      Eighteen club ice hockey players were recruited to participate in this study.
      ASSESSMENT OF RISK FACTORS: A standard emergency log roll was performed 3 times
      under each of 3 different helmet fit conditions: properly fit, improperly
      (competition) fit, and helmet-removed. MAIN OUTCOME MEASUREMENTS: Frontal,
      sagittal, and transverse plane cervical spine motion were used as outcome
      measures. RESULTS: Significantly less sagittal and transverse plane motion
      occurred during the helmet-removed condition. No differences in frontal plane
      motion among the 3 conditions were observed. CONCLUSIONS: Presence of helmet
      (whether properly fit or not) resulted in increased of sagittal and transverse
      plane movement. This suggests that when an ice hockey helmet is stabilized, the
      head within it is not. We recommend the helmet and face shield be removed before
      performing an emergency prone log roll.

PMID- 18806546
TI  - Injuries to the head and face in women's collegiate field hockey.
AB  - OBJECTIVE: To investigate the incidence and severity of head and facial injuries
      in female collegiate field hockey players. DESIGN: Prospective, survey-based
      study. SETTING AND PARTICIPANTS: Certified athletic trainers and athletes at 6
      Division I institutions. INTERVENTIONS/ASSESSMENT OF RISK FACTORS: Head and
      facial injuries were documented during practices and games during 2 women's field
      hockey seasons. MAIN OUTCOME MEASUREMENTS: The total number of incidents that
      resulted in a head or facial injury, the total number of head and facial
      injuries, the injury type, location, and source, and the amount of time the
      injured athlete lost from play. When the injury occurred, either in a game or
      practice, was documented in year 2. RESULTS: A total of 253 student-athlete
      seasons (each season that a player competed was considered 1 student-athlete
      season) were completed. A total of 57 incidents occurred with 62 head and facial
      injuries reported (5 incidents yielded 2 injuries each). Most injuries were due
      to contact with the ball (56%); the majority of injuries were lacerations (32%).
      A relatively high number of facial fractures were reported (13%). Sixty-five
      percent of the injuries resulted in less than 1-day time loss and would not have
      been reportable in many traditional injury surveillance systems. CONCLUSIONS: The
      high number and rate of serious or potentially serious injuries occurring to the
      head and face in female collegiate field hockey players is a concern. Prevention
      measures, including better protective equipment for the head and face, may help
      reduce future head and facial injuries in these athletes.

PMID- 18806547
TI  - The comparative incidence of reported concussions presenting for follow-up
      management in South African Rugby Union.
AB  - OBJECTIVE: The objective of this study was to compare the seasonal concussion
      incidence for school, university, club and provincial level Rugby Union players
      in South Africa. DESIGN: The study presents a retrospective statistical analysis
      of the number of reported concussions documented annually for groups of Rugby
      Union players as a proportion of those who received preseason neurocognitive
      assessment. SETTING: Between 2002 and 2006, concussion management programs using
      computerized neuropsychological assessment were implemented for clinical and
      research purposes by psychologists in selected South African institutions
      involved in Rugby Union from school through to the professional level.
      PARTICIPANTS: The incidence figures were based on 175 concussive episodes
      reported for 165 athletes who were referred for neurocognitive assessment from a
      population of 1366 athletes who received preseason baseline testing.
      INTERVENTIONS: Concussion management routines varied according to the protocols
      adopted by the different psychologists and rugby organizations. MAIN OUTCOME
      MEASUREMENTS: It was expected that the incidence of concussion would vary
      significantly due to level of play and different management protocols. RESULT:
      There was wide disparity in the manner in which concussion follow-up was managed
      by the various organizations. Within broadly comparable cohorts, tighter control
      was associated with a relatively higher concussion incidence for athletes per
      rugby playing season, with average institutional figures ranging from 4% to 14%
      at school level and 3% to 23% at adult level. CONCLUSIONS: This analysis suggests
      that concussion goes unrecognized and therefore incorrectly managed in a number
      of instances. Recommendations for optimal identification of concussed athletes
      for follow-up management are presented.

PMID- 18806548
TI  - The effect of concentrating periods of physical activity on the risk of injury in
      organized sports in a pediatric population.
AB  - BACKGROUND: The trend in pediatric sport organizations is to regroup activities
      into tournaments. Sports-related injuries in children are a public concern.
      OBJECTIVE: To evaluate the association between sport injuries and consolidation
      of physical activity in children. DESIGN: A case-crossover study. SETTING: The
      emergency department of a tertiary care hospital for approximately 1 year in
      2006. PARTICIPANTS: Eligible participants had to be between 8 to 16 years of age,
      presenting to the emergency department for an acute injury that occurred during a
      timed organized sport event. ASSESSMENT OF RISK FACTORS: A standardized
      questionnaire was used to evaluate the number of hours of organized physical
      activity, which was defined as a supervised exercise leading to competitions. The
      number of hours of activity was compared between case periods (48 hours and 7
      days) and control periods of same length. MAIN OUTCOME MEASUREMENTS: An injury
      was defined as any acute problem with organic tissue that occurred during a
      sport. RESULTS: On average, participants performed 136 minutes of organized sport
      activity in the 48 hours preceding the injury for a mean difference of 8 +/- 18
      min. They also performed 356 minutes of organized sports in the 7 days prior the
      injury. This represented an increase of 40 +/- 31 minutes compared to the control
      periods. CONCLUSIONS: More injuries were observed if the athletes had increased
      the concentration of activity in the 7 days prior. Although small, this
      difference reflected a minor clinical effect. In our study, we failed to disclose
      an association for the period of 48 hours.

PMID- 18806549
TI  - Altered force ratio in unanticipated side jumps after treadmill run.
AB  - OBJECTIVE: The aim was to investigate the influence of a run at the individual
      anaerobic threshold (IAT) on postural control in jumps with an unanticipated
      change of direction. HYPOTHESIS: Dynamic postural control is less affected by the
      run in trained athletes than in recreational ones. DESIGN: : Controlled
      prospective cohort study with an intervention. SETTING: Biomechanics laboratory.
      PARTICIPANTS: A total of 18 female high-level handball and volleyball players, 16
      female and 8 male recreational athletes, with a mean age of 21.7 +/-4.1 years.
      INTERVENTIONS: In the jump test, the ball switch, hit above the force plate
      during a forward jump, triggers indicator lamps on either side. After landing on
      the dominant leg, a second jump 90 degrees sideways following a light signal or a
      stabilization in one-leg stance was required. Nine jumps (randomized order) were
      performed before and at 1, 5, 10, 15 and 20 min after a 30-min treadmill run at
      the IAT. MAIN OUTCOME MEASUREMENTS: For the second jump, the ratio of the
      absolute values of the maximum forces in anteroposterior and mediolateral
      direction was calculated as a parameter of dynamic postural control in the change
      of direction. RESULTS: In both groups, the force ratio increased significantly at
      1 and 5 min after the treadmill run. The relative increase did not differ between
      groups. Dynamic postural control in transfer from a forward to a sideward jump
      was reduced after the run. Recovery occurred within 10 min. CONCLUSIONS: This
      study shows that dynamic postural control in jumps with an unanticipated change
      of direction is influenced by fatigue. These findings could be used to develop
      training programs aimed at reducing lower limb injuries in high-level ball sport
      athletes. The preventive effects have to be evaluated in further studies.

PMID- 18806550
TI  - Time-course of changes in inflammatory and performance responses following a
      soccer game.
AB  - OBJECTIVE: : To study the effects of a single soccer game on indices of
      performance, muscle damage, and inflammation during a 6-day recovery period.
      DESIGN: : Participants were assigned to either an experimental group (E, played
      in the game; n = 14) or a control group (C, did not participate in the game; n =
      10). SETTING: : Data were collected on a soccer field and at the Physical
      Education and Sports Science laboratory of the Democritus University of Thrace
      before and after the soccer game. PARTICIPANTS: : Twenty-four elite male soccer
      players (age, 20.1 +/- 0.8 years; height, 1.78 +/- 0.08 m; weight, 75.2 +/- 6.8
      kg). MAIN OUTCOME MEASUREMENTS: : Muscle strength, vertical jumping, speed, DOMS,
      muscle swelling, leukocyte count, creatine kinase (CK), lactate dehydrogenase
      (LDH), C-reactive protein (CRP), cortisol, testosterone, cytokines IL-6 and IL
      1b, thioburbituric acid-reactive substances (TBARS), protein carbnyls (PC), and
      uric acid (UA). RESULTS: : Performance deteriorated 1 to 4 days post-game. An
      acute-phase inflammatory response consisted of a post-game peak of leukocyte
      count, cytokines, and cortisol, a 24-hour peak of CRP, TBARS, and DOMS, a 48-hour
      peak of CK, LDH, and PC, and a 72-hour peak of uric acid. CONCLUSION: : A single
      soccer game induces short-term muscle damage and marked but transient
      inflammatory responses. Anaerobic performance seems to deteriorate for as long as
      72-hour post-game. The acute phase inflammatory response in soccer appears to
      follow the same pattern as in other forms of exercise. These results clearly
      indicate the need of sufficient recovery for elite soccer players after a game.

PMID- 18806551
TI  - Characterizing the perception of the placebo effect in sports medicine.
AB  - OBJECTIVE: To characterize differences in the perception and understanding of the
      placebo effect between sports physicians, coaches, athletes, and sports science
      personnel. DESIGN: A short 11-item questionnaire was administered addressing
      demographic details, understanding of the placebo effect, and willingness to use
      the effect in an elite sport setting. SETTING: All participants were involved in
      national level sporting programs. PARTICIPANTS: A total of 187 individuals (17
      sports physicians, 44 sports scientists, 30 national-level coaches, and 96
      national-level athletes) completed the questionnaire. All participants were
      contacted and invited to participate voluntarily. INTERVENTIONS/ASSESSMENT OF
      RISK FACTORS: Not applicable. MAIN OUTCOME MEASUREMENTS: Self-reported responses
      on understanding and use of placebo effect in sport. RESULTS: A total of 94% of
      physicians and 98% of scientists, but only 44% of athletes, indicated a good
      understanding of the placebo effect. A majority of scientists (63%) and
      physicians (59%) administered placebo at least once a year. Most of scientists
      (95%) and a majority of physicians (71%) either mildly or strongly encouraged use
      of the placebo in their clinical practice. About 60% of athletes indicated they
      would not care if they were unknowingly administered a placebo: however, 30% of
      them would not appreciate being misled. CONCLUSIONS: There is a substantial
      difference in the level of understanding of the placebo effect between physicians
      and athletes in elite sport. Although athletes are willing to use the placebo
      effect, physicians need to be mindful of the manner of its implementation.

PMID- 18806552
TI  - Clinical and laboratory evaluation of upper respiratory symptoms in elite
      athletes.
AB  - OBJECTIVE: To characterize the etiology of upper respiratory symptoms in elite
      athletes presenting to a sports physician for treatment. DESIGN: Prospective
      clinical and laboratory investigations. SETTING: Sports medicine clinic.
      PARTICIPANTS: Seventy elite-level athletes. MAIN OUTCOME MEASUREMENTS: Physician
      recorded symptoms and diagnosis; health/training questionnaires; laboratory
      investigations of respiratory pathogens, white blood cell differential counts,
      and immune parameters. RESULTS: Physicians characterized 89% of presentations as
      viral or bacterial upper respiratory tract infection. Only 57% of presentations
      were associated with an identified pathogen or other laboratory parameters
      indicative of infection. Demographic information, previous illness, and training
      history did not distinguish between presentations with or without objective
      measures of infection. Elevated white blood cell and neutrophil counts and lower
      vitamin D concentrations partially distinguished infectious episodes. The number
      of systemic symptoms/behaviors at presentation (cough, headache, earache,
      fatigue, fever/rigors, myalgia/arthralgia, or cessation of training before clinic
      attendance) had some predictive value for infection: odds ratio per symptom, 1.23
      (90% confidence interval: 0.91 to 1.66); probability of infection, 48% with no
      symptoms to 77% with 6 symptoms. Laboratory investigation identified allergy in a
      considerable proportion of the cohort (39%). CONCLUSIONS: The discrepancy between
      physician and laboratory diagnosed infection in elite athletes highlights the
      need for consideration of alternate diagnostic options when evaluating upper
      respiratory symptoms in athletes. A considerable proportion of episodes of
      respiratory symptoms in athletes were not associated with identification of a
      respiratory pathogen; other potentially treatable causes of upper respiratory
      symptoms should be considered, particularly in athletes with recurrent symptoms.

PMID- 18806553
TI  - Effectiveness of sports massage for recovery of skeletal muscle from strenuous
      exercise.
AB  - OBJECTIVE: Sport massage, a manual therapy for muscle and soft tissue pain and
      weakness, is a popular and widely used modality for recovery after intense
      exercise. Our objective is to determine the effectiveness of sport massage for
      improving recovery after strenuous exercise. DATA SOURCES: We searched MEDLINE,
      EMBASE, and CINAHL using all current and historical names for sport massage.
      Reference sections of included articles were scanned to identify additional
      relevant articles. STUDY SELECTION: Study inclusion criteria required that
      subjects (1) were humans, (2) performed strenuous exercise, (3) received massage,
      and (4) were assessed for muscle recovery and performance. Ultimately, 27 studies
      met inclusion criteria. DATA EXTRACTION: Eligible studies were reviewed, and data
      were extracted by the senior author (TMB). The main outcomes extracted were type
      and timing of massage and outcome measures studied. DATA SYNTHESIS: Data from 17
      case series revealed inconsistent results. Most studies evaluating post-exercise
      function suggest that massage is not effective, whereas studies that also
      evaluated the symptoms of DOMS did show some benefit. Data from 10 randomized
      controlled trials (RCTs) do, however, provide moderate evidence for the efficacy
      of massage therapy. The search identified no trend between type and timing of
      massage and any specific outcome measures investigated. CONCLUSIONS: Case series
      provide little support for the use of massage to aid muscle recovery or
      performance after intense exercise. In contrast, RCTs provide moderate data
      supporting its use to facilitate recovery from repetitive muscular contractions.
      Further investigation using standardized protocols measuring similar outcome
      variables is necessary to more conclusively determine the efficacy of sport
      massage and the optimal strategy for its implementation to enhance recovery
      following intense exercise.

PMID- 18806554
TI  - Arthroscopic repair of isolated subscapularis avulsion injuries in adolescent
      athletes.

PMID- 18806555
TI  - Cervical spine injuries in aquaparks.

PMID- 18806556
TI  - Case report: action-induced focal dystonia in long distance runners.

PMID- 18806558
TI  - Salbutamol in athletes.

PMID- 18806559
TI  - Which interventions prevent sport injuries? A review.

PMID- 18806560
TI  - Do cardiorespiratory fitness and maintaining normal body mass reduce risk of
      hypertension?

PMID- 18806561
TI  - Effects of aerobic and resistance exercise on glycemic control.

PMID- 18806562
TI  - Periarticular hyaluronic Acid as an adjunct to standard care for acute ankle
      sprain.

PMID- 18806563
TI  - Quantitative assessment of FDG uptake in brown fat using standardized uptake
      value and dual-time-point scanning.
AB  - OBJECTIVES: Brown fat is a potential source of false-positive findings on FDG
      PET. The purpose of this study was to show the variability in body distribution
      of brown fat, the degree of FDG uptake, the changes on dual-time-point scanning,
      and determine if dual-time-point scanning can help in differentiating brown fat
      from malignant lesions. METHODS: Thirty-two patients were included in this
      retrospective study (14 male, 18 female, age range: 8-72 years). All patients had
      hypermetabolic brown fat activity on FDG PET imaging confirmed by computed
      tomography (CT) scanning. All patients underwent 2 sequential FDG PET scanning
      (dual-time-point imaging). The average percent change in maximum standardized
      uptake value (SUVmax) for 120 brown fat spots between time point 1 and time point
      2 was calculated. RESULTS: Body distribution of hypermetabolic brown fat in the
      32 patients included supraclavicular area (n = 7); cervical and supraclavicular
      (n = 5); cervical, supraclavicular, and axillae (n = 5); cervical area,
      supraclavicular, axillae, and paravertebral (n = 8); supraclavicular, cervical,
      axillae, paravertebral, and mediastinum (n = 4); supraclavicular, cervical,
      axillae, paravertebral, and upper abdomen (n = 2); and supraclavicular, cervical,
      axillae, paravertebral, mediastinum, and intercostals (n = 1). SUVmax for brown
      fat spots ranged from 0.8 to 12.4 and mean SUV was 4.6 + 1.6. On dual-time-point
      imaging, 91 (76%) of the brown fat spots demonstrated an increase in SUVmax that
      ranged from 12% to 192% and mean value of 42%, whereas 16 (13%) brown fat spots
      did not show any change and 11 (11%) spots underwent a drop in SUVmax by 4% to
      12%. There was an increase in the number of active brown fat spots in 3 patients
      on the second time images. CONCLUSIONS: Brown fat is a potential source of false
      positives, which has wide variability in distribution and degree of FDG uptake.
      On dual-time-point scanning, there is a progressive increase in FDG uptake within
      most of the hypermetabolic brown fat areas that mimic malignant lesions.

PMID- 18806564
TI  - Radioguided reoperative parathyroidectomy for persistent primary
      hyperparathyroidism.
AB  - We report a case of reoperative radioguided parathyroidectomy in a patient with
      primary hyperparathyroidism. A 58-year-old man presented to our center with
      persistent hypercalcemia and hyperparathyroidism after 2 previous parathyroid
      explorations at an outside facility. Despite the use of preoperative and
      intraoperative localization, identification of the hyperfunctioning gland was
      unsuccessful during the initial operations. Because of the continued presence of
      symptoms, the patient was referred to our center for reoperation. Repeat Tc-99m
      sestamibi parathyroid scan showed an inferior right parathyroid adenoma. With the
      intraoperative guidance of a hand-held gamma probe, an enlarged parathyroid gland
      was localized on the spine behind the esophagus on the right, and successfully
      removed. Intraoperative parathyroid hormone testing confirmed a surgical cure.
      The use of radioguidance and intraoperative parathyroid hormone testing were
      essential to the successful resection. The patient remained disease-free at
      follow-up.

PMID- 18806565
TI  - C-11 choline PET/CT imaging for differentiating malignant from benign prostate
      lesions.
AB  - PURPOSE: To investigate the potential of C-11 choline PET/CT imaging for
      differentiating prostate cancer (PCa) from benign prostate hyperplasia (BPH).
      MATERIALS AND METHODS: Forty-nine patients with prostate lesions underwent C-11
      choline PET/CT imaging that was performed 5 minutes after injection of 7.4 MBq/kg
      (0.2 mCi/kg C-11 choline in the supine position over 2 bed positions (3 minutes
      per position), covering the pelvis, and the whole body (6 bed) when necessary.
      After attenuation correction, PET data were analyzed visually and
      semiquantitatively by measuring maximum standardized uptake value (SUVmax) of the
      prostate lesions (target) and the muscles (nontarget) and calculating their
      ratios (P/M). RESULTS: Twenty-one PCa and 28 BPH lesions were proven
      histologically. The mean values of the SUVmax of PCa and BPH were 7.87 +/- 5.74
      and 4.95 +/- 5.14, respectively without a significant difference between these 2
      groups (t = 2.02; P > 0.05). The mean P/M of PCa and BPH were 4.21 +/- 1.61 and
      1.87 +/- 0.98. The statistical difference of P/M between them was significant (t
      = 2.04; P < 0.01). Using 2.3 (P/M) as the criterion, C-11 choline PET/CT imaging
      showed a sensitivity of 90.48%, a specificity of 85.71%, and a negative
      predictive value of 92.31%. PET/CT precise localization of the hot spot in
      different parts of the prostate could contribute to the diagnosis. CONCLUSIONS: C
      11 choline PET/CT is a valuable noninvasive imaging technology in the diagnosis
      of PCa. The parameter P/M could differentiate PCa from benign lesions better than
      SUV.

PMID- 18806566
TI  - Anterior abdominal wall uptake in intrahepatic arterial brachytherapy with
      yttrium-90 sir spheres for hepatic malignancy.
AB  - Patients with primary or secondary liver cancer who are not suitable for surgical
      resection may be treated with selective internal radiation therapy with yttrium
      90. This may cause down staging of the tumor to a resectable size in some
      patients, and in these and other patients may prolong survival. It delivers a
      high dose of radiation therapy directly to the tumor, thus minimizing exposure to
      liver sensitive to radiation. Prior scanning with Tc-99m macroaggregated albumin
      is performed to assess lung shunting and potential extrahepatic deposition, which
      can cause significant clinical sequelae. Two patients with hepatic malignancy are
      presented who demonstrated extrahepatic deposition of Tc-99m macroaggregated
      albumin in the anterior abdominal wall. This is thought to be related to a patent
      hepatic falciform ligament artery.

PMID- 18806567
TI  - Improved discrimination of benign and malignant lesions on FDG PET/CT, using
      comparative activity ratios to brain, basal ganglia, or cerebellum.
AB  - PURPOSE: This study demonstrates a simple background correction method, which
      improves the discrimination of benign from malignant lesions on FDG PET-CT
      imaging, using activity ratios compared with brain, basal ganglia, or cerebellum.
      METHODS: Standardized uptake values (SUVs) and comparative activity ratios (CARs)
      were determined for FDG uptake in 92 lesions (39 benign and 53 malignant) in 49
      patients. Reference tissues included cerebral cortex, basal ganglia, cerebellum,
      lung, liver, and aortic blood pool. Discriminant power for each CAR was evaluated
      as malignant-to-benign ratio of mean uptake and ratio of intermediate-likelihood
      lesions to total number of lesions. RESULTS: Uncorrected SUV varied widely for
      malignant and benign lesions, with considerable overlap. Ratio of mean uptake for
      malignant lesions versus benign lesions was lowest for uncorrected SUVAVG and
      SUVAVG/liver (1.92), and highest for SUVMAX/cerebral cortex (3.52). Lesions could
      be separated into very high (> 90%), very low (< 10%), and intermediate (> or =
      10% and < or = 90%) likelihood of malignancy. The ratio of intermediate
      likelihood lesions to the total number of lesions was greatest for SUVAVG (0.42)
      and lowest for SUVMAX/basal ganglia (0.22). CONCLUSIONS: Ability to discriminate
      malignant from benign lesions was enhanced by using CARs derived from cerebral
      cortex, basal ganglia, or cerebellum. Using a 3-tiered diagnostic schema, most
      lesions could be assigned to categories of very high or very low likelihood of
      malignancy, with a significant reduction in indeterminant lesions, compared with
      uncorrected SUV.

PMID- 18806568
TI  - F-18 FDG PET imaging of GVHD-associated polymyositis.

PMID- 18806569
TI  - Cure of neuroendocrine carcinoma by peptide receptor radionuclide therapy.

PMID- 18806570
TI  - Marginal zone lymphoma involving subcutaneous fat: appearance by FDG-PET/CT, MRI,
      and contrast-enhanced CT imaging.

PMID- 18806571
TI  - PET/CT appearance of non-Hodgkin lymphoma of the vermiform appendix.

PMID- 18806572
TI  - Inducing resectability of chemotherapy refractory colorectal liver metastasis by
      radioembolization with yttrium-90 microspheres.

PMID- 18806573
TI  - Bone SPECT/CT detection of a sequestrum in chronic-infected nonunion of the
      tibia.

PMID- 18806574
TI  - Atypical presentation of hypertrophic pulmonary osteoarthropathy on Tc-99m MDP
      bone scintigraphy.

PMID- 18806575
TI  - Additional benefit of SPECT-CT in investigating heel pain.

PMID- 18806576
TI  - Bone marrow granulomatous inflammation: FDG PET findings mimicking hematopoietic
      malignancy.

PMID- 18806577
TI  - Focal uptake in the capitate bone secondary to erosive seronegative arthropathy
      misdiagnosed as fracture.

PMID- 18806578
TI  - Bone scintigraphy for the evaluation of possible osteomyelitis in the lower
      extremity leads to the detection of a brain abscess.

PMID- 18806579
TI  - Unusual ventilation-perfusion scans in the follow-up of two lung transplant
      patients.

PMID- 18806580
TI  - A case of cerebello-thalamo-cortical diaschisis.

PMID- 18806581
TI  - Tc-99m TRODAT findings in a mercury-exposed worker.

PMID- 18806582
TI  - Bladder ear: a potential source of false interpretation on F-18 FDG PET.

PMID- 18806583
TI  - Metastasis to psoas muscle detected by F-18 FDG PET-CT imaging.

PMID- 18806584
TI  - Malignant right coronary artery anomaly identified by multidetector computed
      tomography and stress myocardial single photon emission computed tomography.

PMID- 18806585
TI  - Detection of double Meckel diverticulum by Meckel scan.

PMID- 18806586
TI  - Does radioiodine treatment change the methylene diphosphonate uptake in a toxic
      thyroid nodule on bone scintigraphy?

PMID- 18806587
TI  - Current readings in nuclear medicine.

PMID- 18806589
TI  - Ambulatory managers and researchers in ambulatory care services.

PMID- 18806590
TI  - Relationship of scheduling interval to missed and cancelled clinic appointments.
AB  - BACKGROUND: The interval between when a clinical appointment is created and when
      it occurs may affect the rate of missed and cancelled appointments, affecting
      access and loss to follow-up, key component of quality. METHODS: We examined this
      relationship in various clinic types across Veterans Health Administration
      clinics nationwide. RESULTS: As the interval increased, the missed appointment
      rate increased from 12.0% at day 1 to 20.3% at day 13, then remained constant.
      Cancellation rates increased steadily from 19% during month 1 to 50% by month 12.
      CONCLUSIONS: Scheduling interval has a modest effect on missed appointment rates
      but a large effect on cancellation rates.

PMID- 18806591
TI  - Quality-related activities in federally supported health centers: do they differ
      by organizational characteristics?
AB  - Recent reports suggest the need for further study of the impact of organizational
      characteristics on quality-related activities in health centers. To better
      understand these issues, a cross-sectional assessment of quality-related
      activities in Health Resources and Services Administration-funded health centers
      was conducted using a mailed questionnaire. Associations between the extent and
      frequency of quality-related activities and organizational characteristics,
      including location, size, and accreditation status, were examined. In general,
      the frequency and type of most quality-related activities did not vary greatly by
      size and location, but differed by accreditation status. The findings can be
      explained in part by Health Resources and Services Administration/Bureau of
      Primary Health Care requirements and implementation of their Accreditation
      Initiative.

PMID- 18806592
TI  - Sustaining quality improvement in community health centers: perceptions of
      leaders and staff.
AB  - The Health Disparities Collaboratives are the largest national quality
      improvement (QI) initiatives in community health centers. This article identifies
      the incentives and assistance personnel believe are necessary to sustain QI. In
      2004, 1006 survey respondents (response rate 67%) at 165 centers cited lack of
      resources, time, and staff burnout as common barriers. Release time was the most
      desired personal incentive. The highest funding priorities were direct patient
      care services (44% ranked no. 1), data entry (34%), and staff time for QI (26%).
      Participants also needed help with patient self-management (73%), information
      systems (77%), and getting providers to follow guidelines (64%).

PMID- 18806593
TI  - Management of behavioral health provider networks in private health plans.
AB  - We explored the techniques used by private health plans or by their contracted
      managed behavioral healthcare organizations (MBHOs) to maintain networks of
      behavioral health providers. In particular, we focused on differences by health
      plans' product types (health maintenance organization, point-of-service plan, or
      preferred provider organization) and contracting arrangements (MBHO contracts,
      comprehensive contracts, or no contracts). More than 94% of products selected
      providers using credentialing standards, particular specialists, or geographic
      coverage. To retain providers viewed as high quality, 54% offer reduced
      administrative burden and 44% higher fees. Only 16% reported steerage to a core
      group of highest-quality providers and few reported an annual bonus or guaranteed
      volume of referrals. Some standard activities are common, but some health plans
      are adopting other approaches to retain higher-quality providers.

PMID- 18806594
TI  - Health plans' disease management programs: extending across the medical and
      behavioral health spectrum?
AB  - Although the disease management industry has expanded rapidly, there is little
      nationally representative data regarding medical and behavioral health disease
      management programs at the health plan level. National estimates from a survey of
      private health plans indicate that 90% of health plan products offered disease
      management for general medical conditions such as diabetes but only 37% had
      depression programs. The frequency of specific depression disease management
      activities varied widely. Program adoption was significantly related to product
      type and behavioral health contracting. In health plans, disease management has
      penetrated more slowly into behavioral health and depression program
      characteristics are highly variable.

PMID- 18806595
TI  - Is there a relationship between physician and facility volumes of ambulatory
      procedures and patient outcomes?
AB  - This study explores associations between patient outcomes (7- and 30-day
      hospitalization and mortality) and healthcare provider (physician and facility)
      volumes of outpatient colonoscopy, cataract removal, and upper gastrointestinal
      endoscopy performed in outpatient surgical settings in Florida. Findings indicate
      that patients treated by high-volume physicians or facilities had lower adjusted
      odds ratios for hospitalizations and mortality. When physician and facility
      volume were assessed simultaneously, physician volume accounted for larger
      effects than facility volume in hospitalization models. When assessing both
      physician and facility volume together for mortality, facility volume was a
      stronger predictor of mortality outcomes at 30 days. Further examinations of
      associations of outpatient physician and facility volumes and patient outcomes
      are suggested.

PMID- 18806596
TI  - Nonurgent use of the emergency department.
AB  - Emergency department (ED) overcrowding by low-acuity patients is a recognized
      problem. There is little in the literature on why patients with minor problems
      and an established primary care physician (PCP) present to the ED. Two hundred
      forty low-acuity patients with a PCP were surveyed regarding their reasons for
      presenting at a University of Colorado ED. Inability to schedule a rapid
      clinic/office appointment, advice by PCP to utilize the ED, and high self
      perceived severity of illness were the primary reasons for ED usage. Increased
      patient education about the range of conditions appropriate for care in the PCP
      office and more availability of office appointments could potentially decrease
      the ED usage by patients with low-acuity problems.

PMID- 18806597
TI  - Integrating disaster preparedness and surge capacity in emergency facility
      planning.
AB  - The ability to adapt and utilize emergency facilities is a critical element in
      responding to surges resulting from man-made and natural events. The current
      stresses on emergency services throughout the country find few adequately
      prepared to effectively absorb a sudden increase in patients along with some of
      the potential special requirements, such as quarantining of epidemic patients and
      mass decontamination. This article reviews major findings of the federally funded
      ER One project, a research initiative that has described a number of facility
      strategies, which should be considered in planning new emergency facilities. An
      early case study in the application of these principles at the recently completed
      Tampa General Hospital emergency service is provided, illustrating how, when
      integrated into the early planning and design, many of the ER One recommendations
      can be implemented at modest capital cost increases.

PMID- 18806599
TI  - What if ... you're examining your first deaf patient?

PMID- 18806600
TI  - Atrial fibrillation and the expanding role of catheter ablation: do
      antiarrhythmic drugs have a future?
AB  - The main therapeutic strategies for treating atrial fibrillation include rate
      control, maintenance of sinus rhythm, and antiembolic treatment. Current
      antiarrhythmic drugs are effective in about 50% of patients and are often
      associated with adverse effects. Multiple trials suggest that rate control with
      proper anticoagulation treatment is associated with a similar prognosis to a more
      aggressive rhythm control strategy. Catheter ablation of atrial fibrillation has
      success rates that exceed currently available antiarrhythmic drugs. However,
      catheter ablation is an evolving technique that can result in complications. In
      some patients, antiarrhythmic drugs are still required following ablation. New
      antiarrhythmic drug strategies include developing drugs that are more atrial
      selective, alteration of the multichannel blocking agent, amiodarone, or the
      development of drugs with novel mechanisms of action such as gap junction
      facilitation of conduction. Although catheter ablation procedures will continue
      to grow, the millions of atrial fibrillation patients who will require therapy
      will continue to make antiarrhythmic drug therapy an important part of our
      ongoing therapeutic armamentarium.

PMID- 18806601
TI  - The place of hybrid therapies with drugs to supplement nonpharmacological
      therapies in atrial fibrillation.
AB  - Atrial fibrillation (AF) is one of the most common cardiac arrhythmias, and its
      prevalence continues to rise as the aged population increases. Comparative
      studies of rhythm control and rate control have been equivocal; however, the
      benefits of rhythm control may have been offset by the limitations of
      antiarrhythmic drugs. More recently, nonpharmacological therapies have emerged
      that provide hope of more effective rhythm control. Catheter ablation techniques
      have gained favour with high success rates in specialized centers, although these
      techniques are not without complications and require considerable expertise.
      Pacing therapies designed to reduce harmful right ventricular pacing and increase
      physiological pacing have shown benefit in AF patients with bradycardia. Despite
      this progress, no single modality confers benefit for all patients. Strategies to
      combine these treatment modalities in a hybrid approach has shown increasing
      promise for subgroups of AF patients.

PMID- 18806602
TI  - Biological therapies for atrial fibrillation.
AB  - Atrial fibrillation is a prominent cause of morbidity and mortality in developed
      countries. Current treatment strategies center on controlling heart rate while
      allowing fibrillation to persist or targeting fibrillation primarily and
      attempting to maintain sinus rhythm. Pharmacological therapies are largely
      successful for rate control, although mild toxicities are common. Rhythm control
      strategies are often unsuccessful, leaving patients in atrial fibrillation
      despite attempts to maintain sinus rhythm. This review will discuss novel
      biological strategies that are currently under development and may eventually
      have impact on the management of atrial fibrillation.

PMID- 18806603
TI  - Estrogen protects the heart from ischemia-reperfusion injury via COX-2-derived
      PGI2.
AB  - There is an accumulating body of data to suggest that estrogen mediates its
      cardioprotective effects via cyclooxygenase activation and synthesis of
      prostaglandins (PG), specifically PGI2. We hypothesized that inhibition of COX-2
      would prevent estrogen's cardioprotective effects after myocardial ischemia
      reperfusion. Acute treatment with 17beta-estradiol (E2; 20 microg/rabbit)
      increased COX-2 protein expression and activity in the myocardium. To determine
      the effects of COX-2 inhibition on infarct size after E2 treatment, New Zealand
      white rabbits were anesthetized and administered the COX-2 inhibitor nimesulide
      (5 mg/kg) or vehicle intravenously 30 minutes before an intravenous injection of
      E2. Thirty minutes after estrogen treatment, the coronary artery was occluded for
      30 minutes followed by 4 hours of reperfusion. E2 significantly decreased infarct
      size as a percent of area at risk when compared to vehicle (18.9 +/- 3.1 versus
      47.0 +/- 4.1; P < 0.001). Pretreatment with nimesulide nullified the infarct size
      sparing effect of E2 (55.8 +/- 5.6). Treatment with the PGI2 receptor antagonist
      RO3244794 also abolished the protective effects of E2 (45.3 +/- 4.5). The results
      indicate that estrogen protects the myocardium from ischemia-reperfusion injury
      through increased production of COX-2-derived PGI2. The data indicate that
      selective COX-2 inhibitors might counteract the potential cytoprotective effects
      of estrogen in premenopausal or postmenopausal women.

PMID- 18806604
TI  - Enhanced Na+/H+ exchange during ischemia and reperfusion impairs mitochondrial
      bioenergetics and myocardial function.
AB  - Inhibition of Na+/H+ exchange (NHE) during ischemia reduces cardiac injury due to
      reduced reverse mode Na+/Ca2+ exchange. We hypothesized that activating NHE-1 at
      buffer pH 8 during ischemia increases mitochondrial oxidation, Ca2+ overload, and
      reactive O2 species (ROS) levels and worsens functional recovery in isolated
      hearts and that NHE inhibition reverses these effects. Guinea pig hearts were
      perfused with buffer at pH 7.4 (control) or pH 8 +/- NHE inhibitor eniporide for
      10 minutes before and for 10 minutes after 35- minute ischemia and then for 110
      minutes with pH 7.4 buffer alone. Mitochondrial NADH and FAD, [Ca2+], and
      superoxide were measured by spectrophotofluorometry. NADH and FAD were more
      oxidized, and cardiac function was worse throughout reperfusion after pH 8 versus
      pH 7.4, Ca2+ overload was greater at 10-minute reperfusion, and superoxide
      generation was higher at 30-minute reperfusion. The pH 7.4 and eniporide groups
      exhibited similar mitochondrial function, and cardiac performance was most
      improved after pH 7.4+eniporide. Cardiac function on reperfusion after pH
      8+eniporide was better than after pH 8. Percent infarction was largest after pH 8
      and smallest after pH 7.4+eniporide. Activation of NHE with pH 8 buffer and the
      subsequent decline in redox state with greater ROS and Ca2+ loading underlie the
      poor functional recovery after ischemia and reperfusion.

PMID- 18806605
TI  - Causes and consequences of zinc dyshomeostasis in rats with chronic
      aldosteronism.
AB  - Iterations in Ca2+ and Mg2+ balance accompany aldosteronism (inappropriate for
      dietary Na+ intake). Increased Zn excretion and Zn translocation to injured
      tissues, including the heart, also occurs. Several causes and consequences of Zn
      dyshomeostasis in rats receiving aldosterone/salt treatment (ALDOST) were
      examined. (1) To study the role of urinary acidification in promoting
      hyperzincuria, acetazolamide (75 mg/kg), a carbonic anhydrase inhibitor, was used
      as cotreatment to raise urinary HCO3 excretion. (2) To assess Zn levels in the
      heart, including cardiomyocyte cytosolic free [Zn2+]i and mitochondrial Zn, the
      expression of metallothionein (MT-I), a Zn binding protein, and biomarkers of
      oxidative stress were examined. (3) Oxidative stress and cardiac pathology in
      response to ZnSO4 supplement (40 mg/d) were also studied. Comparison of controls
      and rats receiving 4 weeks ALDOST revealed the following: (1) an acidification of
      urine and metabolic alkalosis associated with increased urinary Zn excretion and
      hypozincemia, each of which were prevented by acetazolamide; (2) a rise in
      cardiac Zn, including increased [Zn2+]i and mitochondrial Zn, associated with
      increased tissue MT-I, 8-isoprostane, malondialdehyde, and gp91(phox), coupled
      with oxidative stress in plasma and urine; (3) ZnSO4 prevented hypozincemia, but
      not ionized hypocalcemia, and attenuated oxidative stress and microscopic
      scarring without preventing the vasculitis and perivascular fibrosis of
      intramural coronary arteries. Thus, the hyperzincuria seen with ALDOST is due to
      urinary acidification. The oxidative stress that appears in the heart is
      accompanied by increased tissue Zn serving as an antioxidant. Cotreatment with
      ZnSO4 attenuated cardiomyocyte necrosis; however, polynutrient supplement may be
      required to counteract the dyshomeostasis of all 3 cations that accompanies
      aldosteronism and contributes to cardiac pathology.

PMID- 18806606
TI  - Effect of L-2286, a poly(ADP-ribose)polymerase inhibitor and enalapril on
      myocardial remodeling and heart failure.
AB  - Increased activation of poly(ADP-ribose) polymerase (PARP) enzyme has been
      implicated in the pathogenesis of acute and chronic myocardial dysfunction. We
      have demonstrated the protective effect of PARP inhibitors against postinfarction
      myocardial remodeling and heart failure. The primary aim of our recent work was
      to compare the effect and efficacy of a potent PARP-inhibitor (L-2286) to
      enalapril, a widely used angiotensin-converting enzyme (ACE) inhibitor. in
      experimental heart failure model. Both L-2286 and enalapril were tested in a rat
      model of chronic heart failure after isoproterenol-induced myocardial infarction.
      After a 12-week treatment period, echocardiography was performed, cardiac
      hypertrophy and interstitial collagen deposition were assessed, and the
      phosphorylation state of Akt-1/GSK-3beta pathway as well as the PKC and MAPK
      kinases were determined. Both PARP and ACE inhibition reduced the progression of
      postinfarction heart failure by attenuating cardiac hypertrophy and interstitial
      fibrosis. More importantly, PARP inhibition increased the activity of the
      prosurvival signal transduction factors (Akt-1/GSK-3beta pathway, PKCepsilon).
      Due to these effects, L-2286 improved the systolic left ventricular function.
      Enalapril treatment exerted a similar, but weaker protective effect against
      postinfarction myocardial remodeling and heart failure. In conclusion, we
      demonstrated in an experimental heart failure model that L-2286 decreased the
      postinfarction myocardial remodeling more effectively than enalapril treatment.

PMID- 18806607
TI  - Acute effect of sidestream cigarette smoke extract on vascular endothelial
      function.
AB  - Acute exposure to passive smoking adversely affects vascular function by
      promoting oxidative stress and endothelial dysfunction. However, it is not known
      whether tobacco sidestream (SS) smoke has a greater deleterious effect on the
      endothelium than non-tobacco SS smoke and whether these effects are related to
      nicotinic endothelial stimulation. To test these hypotheses, endothelial
      dependent relaxation and superoxide anion production were assessed in isolated
      rat aortas incubated with tobacco SS smoke, non-tobacco SS smoke, or pure
      nicotine. Tobacco SS smoke decreased the maximal relaxation to acetylcholine
      (Ach) from 79 +/- 6% to 57 +/- 7.3% (% inhibition of phenylephrine-induced
      plateau, P < 0.001) and increased superoxide anion production from 31 +/- 9.7 to
      116 +/- 24 count/10 sec/mg (P < 0.01, lucigenin-enhanced chemiluminescence
      technique). The non-tobacco SS smoke extract had no significant effect on the
      response to Ach but increased superoxide anion production in the aortic wall to
      133 +/- 2 count/10 sec/mg (P < 0.001). Furthermore, concentration-response curves
      to Ach and superoxide production remained unaltered with nicotine (0.001, 0.01,
      or 0.1 mM). In conclusion, despite similar increases in vascular wall superoxide
      production with tobacco and non-tobacco SS smoke, only the tobacco SS smoke
      extracts affected endothelium-dependent vasorelaxation. Nicotine alone does not
      reproduce the effects seen with tobacco SS smoke, suggesting that the acute
      endothelial toxicity of passive smoking cannot simply be ascribed to a nicotine
      dependent mechanism.

PMID- 18806608
TI  - TVP1022 and propargylamine protect neonatal rat ventricular myocytes against
      doxorubicin-induced and serum starvation-induced cardiotoxicity.
AB  - We recently reported that propargylamine derivatives such as rasagiline (Azilect)
      and its S-isomer TVP1022 are neuroprotective. The aim of this study was to test
      the hypothesis that the neuroprotective agents TVP1022 and propargylamine (the
      active moiety of propargylamine derivatives) are also cardioprotective. We
      specifically investigated the protective efficacy of TVP1022 and propargylamine
      in neonatal rat ventricular myocytes (NRVM) against apoptosis induced by the
      anthracycline chemotherapeutic agent doxorubicin and by serum starvation. We
      demonstrated that pretreatment of NRVM cultures with TVP1022 or propargylamine
      attenuated doxorubicin-induced and serum starvation-induced apoptosis, inhibited
      the increase in cleaved caspase 3 levels, and reversed the decline in Bcl-2/Bax
      ratio. These cytoprotective effects were shown to reside in the propargylamine
      moiety. Finally, we showed that TVP1022 neither caused proliferation of the human
      cancer cell lines HeLa and MDA-231 nor interfered with the anti-cancer efficacy
      of doxorubicin. These results suggest that TVP1022 should be considered as a
      novel cardioprotective agent against ischemic insults and against anthracycline
      cardiotoxicity and can be coadministered with doxorubicin in the treatment of
      human malignancies.

PMID- 18806609
TI  - Effects of angiotensin-1 converting enzyme inhibition on oxidative stress and
      bradykinin receptor expression during doxorubicin-induced cardiomyopathy in rats.
AB  - To evaluate the mechanisms and the impact of the angiotensin-converting enzyme
      inhibitor perindopril (P) in a model of doxorubicin (D)-induced cardiotoxicity,
      male Wistar rats received D (1 mg/kg/d, IP for 10 days), P (2 mg/kg/d by gavage
      from day 1 to day 18), D (for 10 days) + P (for 18 days) or saline. D decreased
      systolic blood pressure and body and heart weights. Left ventricular diastolic
      diameter was increased by D (P < 0.01), but it was not attenuated by P. D
      decreased plasma vitamin C (P < 0.05) and increased the ascorbyl radical/vitamin
      C ratio (P < 0.01). This ratio was attenuated by P. No difference was found among
      groups in cardiac troponin I, brain natriuretic peptide concentrations, and
      tissue oxidative stress (OS). Myocardial MCP-1 expression was higher in the D
      group. Cardiac kinin receptor (B1R and B2R) expression was not affected by D, yet
      binding sites for B2R and B1R were increased in D+P and P groups, respectively (P
      < 0.05). In conclusion, D induced cardiac functional alterations, inflammation
      and plasma OS whereas tissue OS, and cardiac kinin receptors expression were not
      modified. P did not improve cardiac performance, but it modulated kinin receptor
      expression and enhanced antioxidant defense.

PMID- 18806610
TI  - Glycogen synthase kinase 3 inhibition protects the heart from acute ischemia
      reperfusion injury via inhibition of inflammation and apoptosis.
AB  - Glycogen synthase kinase (GSK)-3beta inhibitors play an anti-inflammatory role in
      several inflammatory diseases. Recent studies have demonstrated that GSK-3beta
      inhibitors protect against myocardial ischemia-reperfusion injury. However, the
      precise mechanisms remain unclear. We aimed to investigate the roles of
      inflammation and apoptosis induced by ischemia-reperfusion in the
      cardioprotection by GSK-3beta inhibitor 4-benzyl-2-methyl-1, 2, 4-thiadiazolidine
      3, 5-dione (TDZD-8). Anaesthetized Sprague-Dawley rats underwent an open-chest
      procedure involving 30 min of myocardial ischemia and 6 h of reperfusion with or
      without TDZD-8 given at reperfusion. TDZD-8 reduced myocardial infarct size by
      nearly 43% (P < 0.05 vs. myocardial ischemia-reperfusion) and attenuated
      myeloperoxidase activity (21.80 +/- 1.07 U/100 mg tissue. vs. myocardial ischemia
      reperfusion group, P < 0.05). Administration of TDZD-8 significantly suppressed
      nuclear factor kappa B (NF-kappaB) and p38 MAPK activation (P < 0.05 vs.
      myocardial ischemia-reperfusion) and the concentrations of the myocardial-derived
      cytokines tumor necrosis factor-alpha (TNF-alpha, 107.40 +/- 7.34 pg/mg protein
      vs. myocardial ischemia-reperfusion group, P < 0.05) and interleukin-6 (IL-6,
      29.28 +/- 6.3 pg/mg protein vs. myocardial ischemia-reperfusion group, P < 0.05).
      Treatment with TDZD-8 also inhibited myocardial cell apoptosis compared with the
      myocardial ischemia-reperfusion group (12 +/- 1% vs. 22 +/- 2%, P < 0.05).
      Therefore, blocking this protein kinase activity may be a novel approach to the
      treatment of this condition, which is characterized by inflammation and
      apoptosis.

PMID- 18806611
TI  - The metabolic syndrome in hypertension: European society of hypertension position
      statement.
AB  - The metabolic syndrome considerably increases the risk of cardiovascular and
      renal events in hypertension. It has been associated with a wide range of
      classical and new cardiovascular risk factors as well as with early signs of
      subclinical cardiovascular and renal damage. Obesity and insulin resistance,
      beside a constellation of independent factors, which include molecules of
      hepatic, vascular, and immunologic origin with proinflammatory properties, have
      been implicated in the pathogenesis. The close relationships among the different
      components of the syndrome and their associated disturbances make it difficult to
      understand what the underlying causes and consequences are. At each of these key
      points, insulin resistance and obesity/proinflammatory molecules, interaction of
      demographics, lifestyle, genetic factors, and environmental fetal programming
      results in the final phenotype. High prevalence of end-organ damage and poor
      prognosis has been demonstrated in a large number of cross-sectional and a few
      number of prospective studies. The objective of treatment is both to reduce the
      high risk of a cardiovascular or a renal event and to prevent the much greater
      chance that metabolic syndrome patients have to develop type 2 diabetes or
      hypertension. Treatment consists in the opposition to the underlying mechanisms
      of the metabolic syndrome, adopting lifestyle interventions that effectively
      reduce visceral obesity with or without the use of drugs that oppose the
      development of insulin resistance or body weight gain. Treatment of the
      individual components of the syndrome is also necessary. Concerning blood
      pressure control, it should be based on lifestyle changes, diet, and physical
      exercise, which allows for weight reduction and improves muscular blood flow.
      When antihypertensive drugs are necessary, angiotensin-converting enzyme
      inhibitors, angiotensin II-AT1 receptor blockers, or even calcium channel
      blockers are preferable over diuretics and classical beta-blockers in
      monotherapy, if no compelling indications are present for its use. If a
      combination of drugs is required, low-dose diuretics can be used. A combination
      of thiazide diuretics and beta-blockers should be avoided.

PMID- 18806612
TI  - Ouabain decreases reactive oxygen species and salvages nitric oxide: or is it the
      other way around?

PMID- 18806613
TI  - The Data from an Epidemiologic Study on the Insulin Resistance Syndrome Study:
      the change and the rate of change of the age-blood pressure relationship.
AB  - OBJECTIVE: Systolic blood pressure (SBP) and diastolic blood pressure (DBP)
      increase significantly until around 55 years, when SBP increases, DBP decreases.
      Whether the rates of change of SBP and DBP with age exhibit a similar
      dissociation has never been investigated. DESIGN AND PARTICIPANTS: The Data from
      an Epidemiologic Study on the Insulin Resistance Syndrome Study (D.E.S.I.R.), a 9
      year longitudinal study included 2278 men and 2314 women, 30-65 years and SBP,
      DBP, and other cardiometabolic risk factors were determined every 3 years.
      RESULTS: Both SBP and DBP increased with age, more rapidly in women than in men.
      SBP and DBP were higher in the presence of risk factors (except smoking) but the
      increases with age were similar. For the rates of change, whereas DeltaSBP
      increased linearly with age, DeltaDBP declined as early as 45 years. This finding
      was not influenced by sex, menopause or other risk factors but was significantly
      attenuated in the presence of hypertension at baseline, whether treated or not,
      and mainly in men. CONCLUSION: DBP increases with age between 30 and 60 years,
      DeltaDBP tends to be markedly reduced as early as 45 years, in contrast with
      DeltaSBP. Consequences for the understanding of vascular aging and
      antihypertensive therapy remain to be explored.

PMID- 18806614
TI  - Blood pressure reference values in adolescents: methodological aspects and
      suggestions for Northern Europe tables based on the Nord-Trondelag Health Study
      II.
AB  - The secular weight increase in European and US adolescents and the increasing use
      of oscillometric devices pose a problem to decide on normative blood pressure
      levels. We studied how biological and statistical aspects influence standards,
      and suggest new Northern Europe reference tables. All adolescents of Nord
      Trondelag county, Norway, aged 13-18 years were invited to the Nord-Trondelag
      Health Study II (1995-1997), and the participation rate was 90% (n = 7682 after
      excluding 278 chronically ill patients). Blood pressure was measured with an
      oscillometric device (Criticare 507N, Criticare Systems Inc., Waukesha,
      Wisconsin, USA). We found that overweight introduced a systematic bias in blood
      pressure results (+3-5 mmHg). In addition to the well known differences with age
      and sex, we found evident 95th percentile differences in systolic blood pressure
      between the tallest and shortest individuals, ranging from 3-17 mmHg, and
      postpubertal status increased systolic blood pressure by 2-4 mmHg. We also found
      that a polynomial regression model with ln(blood pressure) as the dependent
      variable better accounted for the higher variation in blood pressure in subgroups
      with higher mean blood pressure. The suggested reference tables have a similar
      50th percentile to British oscillometric data (1-4 mmHg above), whereas our 95th
      percentiles were 4-7 mmHg above. Compared with US sphygmomanometric data, our
      values range 5-12 and 10-16 mmHg above, respectively. We conclude that all blood
      pressure reference tables for adolescents should be region specific and based on
      normal-weight individuals. In addition to age and sex, height, puberty, type of
      measurement device and different variances in different age groups should also be
      accounted for.

PMID- 18806615
TI  - Ambulatory blood pressure monitoring versus self-measurement of blood pressure at
      home: correlation with target organ damage.
AB  - OBJECTIVE: Ambulatory blood pressure (BP) monitoring and home blood pressure
      measurements predicted the presence of target organ damage and the risk of
      cardiovascular events better than did office blood pressure. METHODS: To compare
      these two methods in their correlation with organ damage, we consecutively
      included 325 treated (70%) or untreated hypertensives (125 women, mean age = 64.5
      +/- 11.3) with office (three measurements at two consultations), home (three
      measurements morning and evening over 3 days) and 24-h ambulatory monitoring.
      Target organs were evaluated by ECG, echocardiography, carotid echography and
      detection of microalbuminuria. Data from 302 patients were analyzed. RESULTS:
      Mean BP levels were 142/82 mmHg for office, 135.5/77 mmHg for home and 128/76
      mmHg for 24-h monitoring (day = 130/78 mmHg; night = 118.5/67 mmHg). With a 135
      mmHg cut-off, home and daytime blood pressure diverged in 20% of patients.
      Ambulatory and Home blood pressure were correlated with organ damage more closely
      than was office BP with a trend to better correlations with home BP. Using
      regression analysis, a 140 mmHg home systolic blood pressure corresponded to a
      135 mmHg daytime systolic blood pressure; a 133 mmHg daytime ambulatory blood
      pressure and a 140 mmHg home blood pressure corresponded to the same organ damage
      cut-offs (Left ventricular mass index = 50 g/m, Cornell.QRS = 2440 mm/ms, carotid
      intima media thickness = 0.9 mm). Home-ambulatory differences were significantly
      associated with age and antihypertensive treatment. CONCLUSION: We showed that
      home blood pressure was at least as well correlated with target organ damage, as
      was the ambulatory blood pressure. Home-ambulatory correlation and their
      correlation with organ damage argue in favor of different cut-offs, that are
      approximately 5 mmHg higher for systolic home blood pressure.

PMID- 18806616
TI  - Monitoring of the central pulse pressure is useful for detecting cardiac overload
      during antiadrenergic treatment: the Japan Morning Surge 1 study.
AB  - OBJECTIVE: Lowering of the central pulse pressure (PP) has been shown to
      contribute to an improvement of the cardiac damage beyond that of lowering the
      brachial PP. We assessed the hypothesis that the change in the central PP is more
      useful than that in the brachial PP in the assessment of the change in cardiac
      load. METHODS: We studied 434 treated hypertensive patients whose home systolic
      blood pressure was 135 mmHg or higher. They were followed for 6 months after
      allocation to either a control group or an added treatment group (doxazosin 1-4
      mg and atenolol when needed). We measured the brachial and central (carotid)
      blood pressure simultaneously using a validated device, and the B-type
      natriuretic peptide at baseline and at the sixth month of treatment. RESULTS: In
      the added treatment group, the brachial systolic blood pressure was successfully
      reduced, but the central PP increased significantly, whereas the other blood
      pressure parameters did not change from the baseline. In the added treatment
      group, the change in the B-type natriuretic peptide was significantly correlated
      with the change in the brachial PP (r = 0.18), central systolic blood pressure (r
      = 0.18), central PP (r = 0.26), and PP amplification (r = -0.22) even after
      adjusting for the confounding factors. The correlation with the central PP was
      stronger than with the brachial PP (P = 0.018) or central systolic blood pressure
      (P = 0.002), and these relationships were essentially the same even after
      adjustment for the use of atenolol or the change in heart rate. CONCLUSION: This
      study showed that the central PP measurement may be more important to assess
      cardiac load than the brachial PP during antiadrenergic treatment.

PMID- 18806617
TI  - Distinct genomic replacements from Lewis correct diastolic dysfunction, attenuate
      hypertension, and reduce left ventricular hypertrophy in Dahl salt-sensitive
      rats.
AB  - BACKGROUND: Hypertension and diastolic heart failure are two common
      cardiovascular diseases that inflict heavy morbidity and mortality, yet
      relatively little is understood about their pathophysiology. The identification
      of quantitative trait loci for blood pressure is important in unveiling the
      causes of polygenic hypertension. Although Dahl salt-sensitive strain is also an
      excellent model for the study of diastolic heart failure, virtually nothing is
      known about the quantitative trait loci determining diastolic heart failure.
      Diastolic dysfunction often represents the onset of diastolic heart failure.
      METHODS: We first characterized the cardiac phenotype of Dahl salt-sensitive
      strain and normotensive Lewis control rats by echocardiography to ascertain
      diastolic function. We then analyzed corresponding features of four newly
      developed and two existing congenic strains, each of which carries a specific
      chromosome substitution of Dahl salt-sensitive strain by its Lewis homologue and
      each lowering blood pressure. RESULTS: Dahl salt-sensitive strain displayed
      diastolic dysfunction that was rectified in two of six congenic strains,
      designated as positive congenic strains, which represent the first rodent models
      exhibiting functional normalization of diastolic dysfunction caused by naturally
      occurring genetic variants. The two positive congenic strains also showed a
      reduction in left ventricular mass. In contrast, four of six congenic strains did
      not change diastolic function despite their blood pressure-lowering effects.
      CONCLUSION: Genes present in the replaced chromosome segments of the two positive
      congenic strains are not commonly known to affect blood pressure, diastolic
      function or left ventricular mass. Consequently, novel prognostic, diagnostic and
      therapeutic strategies for hypertensive diastolic heart failure likely emerge
      from this work.

PMID- 18806618
TI  - Ouabain treatment increases nitric oxide bioavailability and decreases superoxide
      anion production in cerebral vessels.
AB  - OBJECTIVE: Chronic administration of ouabain induces hypertension and increases
      the contribution of nitric oxide to vasoconstrictor responses in peripheral
      arteries. The aim of this study was to analyse whether ouabain treatment alters
      the nitric oxide bioavailability in cerebral arteries. METHODS: Basilar arteries
      from control and ouabain-treated rats ( approximately 8.0 microg/day, 5 weeks)
      were used. Vascular reactivity was analysed by isometric tension recording,
      protein expression by western blot, nitric oxide levels by diaminofluorescein
      induced fluorescence, superoxide anion (O2) production by ethidium fluorescence
      and lucigenin chemiluminescence and plasma total antioxidant status by a
      commercial kit. RESULTS: The relaxations induced by bradykinin (1 nmol/l-10
      micromol/l) and L-arginine (0.01-300 micromol/l) and the contractile responses
      induced by both N-nitro-L-arginine methyl ester (0.1-100 micromol/l) and
      oxyhaemoglobin (0.01-10 micromol/l) were greater in arteries from ouabain-treated
      than control rats. However, the relaxation to diethylamine NONOate-nitric oxide
      (0.1 nmol/l-10 micromol/l) and the contractions to KCl (7.5-120 mmol/l) and 5
      hydroxytryptamine (0.01-10 micromol/l) were similar in arteries from both groups.
      Ouabain treatment increased basal nitric oxide levels but did not modify
      endothelial and neuronal nitric oxide synthase protein expression. O2 production
      was lower in cerebral arteries from ouabain-treated rats; however, plasma total
      antioxidant status and vascular protein expression of Cu/Zn-superoxide dismutase,
      Mn-superoxide dismutase and extracellular superoxide dismutase were similar in
      both groups. CONCLUSION: Chronic ouabain treatment increased nitric oxide basal
      levels in basilar arteries probably due to the decreased O2 levels. This might be
      an adaptive mechanism of the cerebral vasculature to the increase in blood
      pressure.

PMID- 18806619
TI  - Chronic urotensin II infusion enhances macrophage foam cell formation and
      atherosclerosis in apolipoprotein E-knockout mice.
AB  - OBJECTIVE: Our recent studies have indicated that urotensin II, the most potent
      vasoconstrictor peptide identified to date, potentiates human macrophage foam
      cell formation and vascular smooth muscle cell proliferation, and its levels are
      increased in the plasma of hypertensive patients with carotid atherosclerotic
      plaques. In the present study, we investigated the enhancing effect of urotensin
      II on atherosclerosis in apolipoprotein E-knockout mice and its suppression by 4
      aminoquinoline, an urotensin II receptor-selective antagonist. METHODS: Urotensin
      II, urotensin II + 4-aminoquinoline, or vehicle was infused for 4 weeks through
      an osmotic mini-pump into 9-week-old apolipoprotein E-knockout mice on a high-fat
      diet. Aortic atherosclerosis and foam cell formation in exudate peritoneal
      macrophages were examined. RESULTS: Atherosclerotic lesions as well as plasma
      levels of urotensin II, reactive oxygen species, and oxidized low-density
      lipoprotein and oxidized low-density lipoprotein-induced foam cell formation were
      significantly greater in urotensin II-infused mice than vehicle-infused controls.
      Western blotting analysis showed increased expression of scavenger receptors
      (CD36 and scavenger receptor class A) and acyl-CoA:cholesterol acyltransferase-1
      in these macrophages. Increases in these parameters were significantly reduced by
      addition of 4-aminoquinoline. In apolipoprotein E-knockout mice even without
      urotensin II infusion, the treatment with 4-aminoquinoline for 8 weeks
      significantly prevented the development of atherosclerotic lesions. CONCLUSION:
      Our results provide the first evidence that increased plasma urotensin II level
      stimulates oxidized low-density lipoprotein and reactive oxygen species
      production and macrophage foam cell formation via increased expression of CD36,
      scavenger receptor class A, and acyl-CoA:cholesterol acyltransferase-1,
      contributing to the development of atherosclerosis in apolipoprotein E-deficient
      mice. Urotensin II receptor antagonism may be a promising therapeutic strategy
      against atherosclerosis.

PMID- 18806620
TI  - Transient receptor potential vanilloid subtype 1 channel mediated neuropeptide
      secretion and depressor effects: role of endoplasmic reticulum associated Ca2+
      release receptors in rat dorsal root ganglion neurons.
AB  - OBJECTIVE: This study tests the hypothesis that the transient receptor potential
      vanilloid subtype 1 channel induced neuropeptide secretion and depressor response
      are mediated by, at least in part, activation of endoplasmic reticulum associated
      Ca release receptors, leading to increased cytosolic Ca in dorsal root ganglion
      neurons. METHODS/RESULTS: Bolus injection of capsaicin (10 or 50 microg/kg), a
      selective transient receptor potential vanilloid subtype 1 channel agonist, into
      anesthetized male Wistar rats caused a dose-dependent decrease in mean arterial
      pressure (P < 0.05). Capsaicin (50 microg/kg)-induced depressor effects and
      increase in plasma calcitonin gene related peptide (CGRP) levels (-29 +/- 2 mmHg,
      82.2 +/- 5.0 pg/ml) were abolished by a selective transient receptor potential
      vanilloid subtype 1 channel antagonist, capsazepine (3 mg/kg, -4 +/- 1 mmHg, 41.8
      +/- 4.4 pg/ml, P < 0.01), and attenuated by a selective ryanodine receptor
      antagonist, dantrolene (5 mg/kg, -12 +/- 1 mmHg, 57.2 +/- 2.6 pg/ml, P < 0.01),
      but unaffected by an inhibitor of endoplasmic reticulum Ca-ATPase, thapsigargin
      (50 microg/kg, -30 +/- 1 mmHg, 73.8 +/- 2.3 pg/ml, P > 0.05), or an antagonist of
      the inositol (1,4,5)-trisphosphate receptor, 2-aminoethoxydiphenyl borate (3
      mg/kg, -34 +/- 5 mmHg, 69.0 +/- 3.7 pg/ml, P > 0.05). CGRP8-37 (1 mg/kg), a
      selective CGRP receptor antagonist, also blocked capsaicin-induced depressor
      effects. In contrast, dantrolene had no effect on CGRP (1 microg/kg)-induced
      depressor effects. In vitro, capsaicin (0.3 micromol/l) increased intracellular
      Ca concentrations and CGRP release from freshly isolated sensory neurons in
      dorsal root ganglion (P < 0.01), which were blocked by capsazepine (10
      micromol/l) and attenuated by dantrolene but not thapsigargin or 2
      aminoethoxydiphenyl borate. CONCLUSION: Our results indicate that transient
      receptor potential vanilloid subtype 1 channel activation triggers ryanodine
      receptor but not inositol (1,4,5)-trisphosphate receptor dependent Ca release
      from endoplasmic reticulum in dorsal root ganglion neurons, leading to increased
      CGRP release and consequent depressor effects.

PMID- 18806621
TI  - Blood pressure around the menopause: a population study.
AB  - BACKGROUND: Hypertension is a major cardiovascular risk factor possibly
      explaining the excessive cardiovascular morbidity and mortality in postmenopausal
      women. Cross-sectional and longitudinal studies have explored this issue with
      diverging results. Our study sought to elucidate the impact of the menopause on
      blood pressure in a representative population sample. METHODS: The study involved
      randomly selected 908 female residents of a Prague district, aged 45-54 years
      (respondence rate, 63.9%). Three definitions of the menopause were used: self
      reported menstrual characteristics (premenopausal with the final menstrual period
      less than 60 days; late menopausal transition, with final menstrual period 60-365
      days; and postmenopausal, final menstrual period more than 365 days before the
      examination), levels of follicle-stimulating hormone (< or = 40 IU/l for
      premenopausal and more than 40 IU/l for postmenopausal women), and both. RESULTS:
      Age-adjusted and BMI-adjusted systolic blood pressure and diastolic blood
      pressure did not differ among the groups regardless of the definition of
      menopause. There was also no difference in the prevalence of hypertension and in
      the age-adjusted and BMI-adjusted odds ratio for hypertension. Multiple
      regression analysis testing the association between systolic blood pressure and
      diastolic blood pressure, and age, BMI, heart rate, smoking, and antihypertensive
      medication explained a rather small proportion of the BP variation. No
      correlation was found between BP and age in either subgroup; the closest
      correlation was always found between BP and BMI. CONCLUSION: In our rather
      homogeneous representative population random sample of women around the
      menopause, the rise in blood pressure after the menopause appeared to be due to
      increased BMI rather than to ovarian failure per se.

PMID- 18806622
TI  - Menopause does not affect blood pressure and risk profile, and menopausal women
      do not become similar to men.
AB  - OBJECTIVE: Menopause is considered to be a cardiovascular risk factor, but this
      belief is based on opinions rather than on evidence. Confounding effects of age
      are often neglected. DESIGN: Population-based study with further subanalysis of
      case-to-case age-matched cohorts of men and fertile and menopausal women.
      SETTING: Epidemiology in primary, public, institutional frame. PARTICIPANTS: Nine
      thousand three hundred and sixty-four men and women aged 18-70 years
      representative of Italian general population followed-up for 18.8 +/- 7.7 years.
      MAIN OUTCOME MEASURES: Blood pressure (BP), prevalence and incidence of
      hypertension, serum total, high-density lipoprotein and low-density lipoprotein
      cholesterol, glucose tolerance, body adiposity, vascular reactivity, target organ
      damage, overall and cardiovascular mortality and morbidity, by gender and by
      menopausal status. RESULTS: Cross-sectional: crude BP, pressor response to cold,
      orthostatic BP decrease, BMI, skinfold thickness, fasting and postload blood
      glucose and insulin, serum lipids, left ventricular mass, serum creatinine,
      microalbuminuria and augmetantion index were higher in menopausal than in fertile
      women, and comparable in menopausal women and men, a difference that was no
      longer present when adjusting for age or considering age-matched cohorts.
      Longitudinal: BP increase during follow-up, cardiovascular mortality and
      morbidity were greater in menopausal than in fertile women, and comparable in
      menopausal women and men, a difference no longer present in age-matched cohorts.
      Menopausal status was rejected from multivariate Cox analysis also including age.
      CONCLUSION: The cardiovascular effects usually attributed to menopause seem to be
      a mere consequence of the older age of menopausal women.

PMID- 18806623
TI  - Reproducibility of the ambulatory arterial stiffness index in hypertensive
      patients.
AB  - BACKGROUND: We studied the repeatability of the ambulatory arterial stiffness
      index (AASI), which can be computed from 24-h blood pressure (BP) recordings as
      unity minus the regression slope of diastolic on systolic BP. METHODS: One
      hundred and fifty-two hypertensive outpatients recruited in Nijmegen (mean age =
      46.2 years; 76.3% with systolic and diastolic hypertension) and 145 patients
      enrolled in the Systolic Hypertension in Europe (Syst-Eur) trial (71.0 years)
      underwent 24-h BP monitoring at a median interval of 8 and 31 days, respectively.
      We used the repeatability coefficient, which is twice the SD of the within
      participant differences between repeat recordings, and expressed it as a
      percentage of four times the SD of the mean of the paired measurements. RESULTS:
      Mean AASI (crude or derived by time-weighted or robust regression) and 24-h pulse
      pressure (PP) were similar on repeat recordings in both cohorts. In Nijmegen
      patients, repeatability coefficients of AASI and PP were approximately 50%. In
      Syst-Eur trial patients, repeatability coefficient was approximately 60% for AASI
      and approximately 40% for PP. For comparison, repeatability coefficients for 24-h
      systolic and diastolic BP were approximately 30%. Differences in AASI between
      paired recordings were correlated with differences in the goodness of fit (r2) of
      the AASI regression line as well as with differences in the night-to-day BP
      ratio. However, in sensitivity analyses stratified for type of hypertension, r2,
      or dipping status, repeatability coefficients for AASI did not widely depart from
      50 to 60% range. CONCLUSION: Estimates of mean AASI were not different between
      repeat recordings, and repeatability coefficients were within the 50-60% range.

PMID- 18806624
TI  - Comparison of aortic pulse wave velocity measured by three techniques: Complior,
      SphygmoCor and Arteriograph.
AB  - BACKGROUND: New 2007 European Society of Hypertension guidelines recommend
      measuring arterial stiffness in patients with arterial hypertension, suggesting a
      carotid-femoral pulse wave velocity over 12 m/s as an estimate of subclinical
      organ damage. Considering this cutoff point, it is worth exploring whether or not
      there are significant differences in results obtained using various techniques
      for measuring aortic pulse wave velocity. The aim of the study was to compare
      aortic pulse wave velocity measurements using Complior, SphygmoCor, and
      Arteriograph devices, and to assess the effect of pulse wave transit time and
      traveled distance on pulse wave velocity values. METHODS: Aortic pulse wave
      velocity was measured on a single visit, using these devices, in randomized
      order, in a group of 64 patients with grade 1 or 2 arterial hypertension.
      RESULTS: Aortic pulse wave velocity measured using Complior (10.1 +/- 1.7 m/s)
      was significantly higher than that obtained using SphygmoCor (8.1 +/- 1.1 m/s) or
      Arteriograph (8.6 +/- 1.3 m/s). No differences were noted between pulse wave
      velocity measurements using SphygmoCor and Arteriograph. Between-method
      comparison revealed that differences in traveled distance were significant:
      Complior versus Arteriograph [0.09 m, Confidence interval (CI): 0.08-0.12 m, P <
      0.05], Complior versus SphygmoCor (0.15 m, CI: 0.13-0.16 m, P < 0.05),
      Arteriograph versus SphygmoCor (0.05 m, CI: 0.03-0.07 m, P < 0.05). No between
      method differences were found for transit times. CONCLUSION: Differences in pulse
      wave velocity obtained by compared devices resulted primarily from using various
      methods for measuring traveled distance. It appears reasonable to establish
      uniform principles for the measurement of traveled distance. Because a large
      number of prognosis/survival studies used direct distance between carotid and
      femoral sites of pulse wave recording, this distance should be mostly
      recommended.

PMID- 18806625
TI  - Protective effect of candesartan in experimental ischemic stroke in the rat
      mediated by AT2 and AT4 receptors.
AB  - OBJECTIVES: The contribution of the AT2 and AT4 angiotensin receptors to the
      protective role of the AT1 receptor blocker candesartan in acute ischemic stroke
      was investigated. METHODS: Embolic stroke was induced by injection of calibrated
      microspheres (50 microm) in the right internal carotid in Sprague-Dawley rats.
      RESULTS: Inhibition of production of endogenous angiotensins by pretreatment for
      24 h with lisinopril significantly increased mortality and infarct volume,
      whereas candesartan for 24 h reduced blood pressure to the same extent but had no
      deleterious effect. A more sustained pretreatment with candesartan for 5 days
      significantly decreased mortality, neurological deficit and infarct size. The AT2
      receptor antagonist PD123319 and the AT4 receptor antagonist divalinal abolished
      the protective effect of 5 days' AT1 blockade. Combined blockade of AT2 and AT4
      in candesartan pretreated rats resulted in an increased mortality, neurological
      deficit and infarct volume of similar magnitude to lisinopril pretreatment.
      Coadministration of lisinopril 24 h before surgery completely blunted the
      protective effect of candesartan pretreatment. Administration of exogenous
      angiotensin IV (1 nmol) reversed the deleterious effect of lisinopril
      pretreatment. CONCLUSION: Protection against acute cerebral ischemia induced by
      AT1 blockade for 5 days is blood pressure independent and mediated by both AT2
      and AT4 angiotensin receptors.

PMID- 18806626
TI  - The impact of hyperacute blood pressure lowering on the early clinical outcome
      following intracerebral hemorrhage.
AB  - OBJECTIVE: Blood pressure lowering in acute intracerebral hemorrhage patients may
      prevent hematoma growth and neurological deterioration. The optimal goal of
      hyperacute antihypertensive therapy for intracerebral hemorrhage patients to
      obtain a favorable early clinical outcome was investigated. METHODS: Of 688
      consecutive patients who were admitted to our stroke care units within 24 h after
      intracerebral hemorrhage onset, 244 patients who emergently received intravenous
      antihypertensive therapy due to admission blood pressure at least 180/105 mmHg
      were assessed. The average systolic and diastolic blood pressure values 6, 12,
      and 24 h after admission and the percentage reduction of the blood pressure value
      with respect to the admission blood pressure value were used for analysis.
      RESULTS: At 3 weeks, 66 patients (27%) had a completely independent activity
      level corresponding to a modified Rankin Scale score of 1 or less. After
      adjustment for baseline characteristics, a favorable functional outcome was more
      common in patients with the lowest quartile of average systolic blood pressure in
      the initial 24 h (<138 mmHg, odds ratio 4.36, 95% confidence interval 1.10
      17.22), and was similarly common in those with the middle two quartiles (138-148
      mmHg, 148-158 mmHg) than in those with the highest quartile of systolic blood
      pressure (> or = 158 mmHg). Analyses using patient quartiles on the basis of the
      average diastolic blood pressure or the reduction of systolic or diastolic blood
      pressure did not show an association with early outcome. CONCLUSION: Lowering the
      systolic blood pressure to less than 138 mmHg during the initial 24 h appears to
      be predictive of favorable early outcome in intracerebral hemorrhage patients.
      Randomized controlled trials to answer this question are needed.

PMID- 18806627
TI  - Role of angiotensin II, endothelin-1 and L-type calcium channel in the
      development of glomerular, tubulointerstitial and perivascular fibrosis.
AB  - OBJECTIVE: Fibrosis is a hallmark of renal damage in several diseases, including
      arterial hypertension. We, therefore, investigated the role of angiotensin II,
      endothelin-1 and of L-type calcium channels in the development of the glomerular,
      vascular, and tubulointerstitial fibrosis in a model of severe angiotensin II
      dependent hypertension. METHODS: Five-week-old Ren-2 transgenic rats (TGRen2)
      received for 4 weeks a placebo, bosentan (100 mg/kg body weight), irbesartan (50
      mg/kg body weight), the ETA-selective endothelin receptor antagonist BMS-182874
      (BMS; 52 mg/kg body weight), the combination of irbesartan (50 mg/kg body weight)
      plus BMS (52 mg/kg body weight), and nifedipine (30 mg/kg body weight). RESULTS:
      Glomerular volume, tubulointerstitial fibrosis, glomerular, and perivascular
      fibrosis were accurately quantified by histomorphometry in four-to-six sections
      per kidney. Glomerular fibrosis was lowered by BMS (P < 0.001), whereas
      tubulointerstitial fibrosis was blunted by bosentan (P < 0.001) and irbesartan (P
      < 0.005). Perivascular fibrosis was reduced by nifedipine and BMS. As only
      irbesartan and irbesartan plus BMS decreased blood pressure (P < 0.001 vs.
      placebo), these effects on fibrosis were independent of blood pressure.
      CONCLUSION: Angiotensin II and L-type calcium channels modulate fibrosis
      selectively in the tubulointerstitial and in the perivascular compartments,
      respectively. The prevention of fibrosis with ET-1 receptor antagonism in all
      three compartments supports a major role of ET-1 in the development of renal
      fibrosis.

PMID- 18806628
TI  - Impaired angiotensin II-extracellular signal-regulated kinase signaling in
      failing human ventricular myocytes.
AB  - Angiotensin II was reported to induce insulin-like growth factor-I and endothelin
      1 gene expression and peptide release by ventricular cardiomyocytes. However, the
      progression from cardiac hypertrophy to failure in humans is characterized by a
      reduced myocyte expression of insulin-like growth factor-I and endothelin-1,
      notwithstanding the enhanced cardiac generation of angiotensin II. In the present
      study we investigated the functional status of the signaling pathways responsible
      for angiotensin II-induced endothelin-1 and insulin-like growth factor-I
      formation in human ventricular myocytes isolated from patients with dilated (n =
      19) or ischemic (n = 14) cardiomyopathy and nonfailing donor hearts (n = 6).In
      human nonfailing ventricular myocytes, angiotensin II (100 nmol/l) induced
      insulin-like growth factor-I and endothelin-1 gene expression, and peptide
      release was mediated by extracellular signal-regulated kinase activation and
      inhibited by extracellular signal-regulated kinase antagonism (PD98059, 30
      micromol/l), endothelin-1 formation being partially reduced also by c-Jun N
      terminal kinase inhibition (SP600125, 10 micromol/l); insulin-like growth factor
      I and endothelin-1 formations were unaffected by the inhibition of p38 mitogen
      activated protein kinase (SB203580, 10 micromol/l) and Janus tyrosine kinase 2
      (AG490, 10 micromol/l). In failing myocytes, angiotensin II failed to induce
      insulin-like growth factor-I and endothelin-1 formation; angiotensin II-induced
      extracellular signal-regulated kinase activation was significantly impaired (-88%
      vs. controls) although c-Jun NH2-terminal kinase activation was preserved. The
      impaired extracellular signal-regulated kinase phosphorylation in failing
      myocytes was associated with increased myocyte levels of mitogen-activated
      protein kinase phosphatases.Therefore, the altered growth factor production in
      failing myocytes is associated with a significant derangement in intracellular
      signaling.

PMID- 18806629
TI  - Implications of persistent prehypertension for ageing-related changes in left
      ventricular geometry and function: the MONICA/KORA Augsburg study.
AB  - BACKGROUND: It is unclear whether persistent prehypertension causes structural or
      functional alterations of the heart. METHODS: We examined echocardiographic data
      of 1005 adults from a population-based survey at baseline in 1994/1995 and at
      follow-up in 2004/2005. We compared individuals who had either persistently
      normal (<120 mmHg systolic and <80 mmHg diastolic, n = 142) or prehypertensive
      blood pressure (120-139 mmHg or 80-89 mmHg, n = 119) at both examinations using
      multivariate regression modeling. RESULTS: Over 10 years, left ventricular end
      diastolic diameters were stable and did not differ between the two groups.
      However, the prehypertensive blood pressure group displayed more pronounced
      ageing-related increases of left ventricular wall thickness (+4.7 versus +11.9%,
      P < 0.001) and left ventricular mass (+8.6 versus +15.7%, P = 0.006).
      Prehypertension was associated with a raised incidence of left ventricular
      concentric remodeling (adjusted odds ratio 10.7, 95% confidence interval 2.82
      40.4) and left ventricular hypertrophy (adjusted odds ratio 5.33, 1.58-17.9). The
      ratio of early and late diastolic peak transmitral flow velocities (E/A)
      decreased by 7.7% in the normal blood pressure versus 15.7% in the
      prehypertensive blood pressure group (P = 0.003) and at follow-up the ratio of
      early diastolic peak transmitral flow and early diastolic peak myocardial
      relaxation velocities (E/EM) was higher (9.1 versus 8.5, P = 0.031) and left
      atrial size was larger (36.5 versus 35.3 mm, P = 0.024) in the prehypertensive
      blood pressure group. Finally, the adjusted odds ratio for incident diastolic
      dysfunction was 2.52 (1.01-6.31) for the prehypertensive blood pressure group.
      CONCLUSIONS: Persistent prehypertension accelerates the development of
      hypertrophy and diastolic dysfunction of the heart.

PMID- 18806630
TI  - Association of physician's sex with risk factor control in treated hypertensive
      patients from Swedish primary healthcare.
AB  - OBJECTIVE: To study the association of physician's sex with blood pressure, lipid
      control, and cardiovascular risk factors in treated hypertensive men and women,
      stratified for the sex of their physician. METHODS: In a cross-sectional survey
      of hypertensive patients, 264 primary care physicians (PCPs), 187 men and 77
      women from across Sweden, recruited 6537 treated hypertensive patients (48% men)
      during 2002-2005, consecutively collected from medical records and registered on
      a web-based form connected to a central database. Patients were included
      consecutively in the same order as they visited the healthcare centre. RESULTS:
      Hypertensive women more often reached target systolic/diastolic blood pressure
      levels (<140/90 mmHg) when treated by female PCPs than when they were treated by
      male PCPs (32 vs. 24%, P < 0.001). This difference remained when comparing female
      and male physicians' nondiabetic female patients. Both male and female patients
      had better control of total cholesterol and low-density lipoprotein cholesterol
      levels when treated by female PCPs than when treated by male PCPs (total
      cholesterol <5 mmol/l: women 30 vs. 24%, P < 0.001; men 42 vs. 34%, P < 0.001;
      low-density lipoprotein cholesterol <3 mmol/l: women 39 vs. 33%, P < 0.01; men 41
      vs. 35%, P < 0.05). Female PCPs had a higher proportion of treated hypertensive
      patients with diabetes than did male PCPs but male PCPs had a higher prevalence
      of treated hypertensive men with microalbuminuria compared with female PCPs.
      CONCLUSION: Female physicians appeared more often to reach the treatment goal for
      blood pressure in female patients and cholesterol levels in all patients than did
      male physicians.

PMID- 18806631
TI  - Prevalence of isolated uncontrolled systolic blood pressure among treated
      hypertensive patients in primary care in Belgium: results of the I-inSYST survey.
AB  - OBJECTIVE: To evaluate the prevalence of isolated uncontrolled systolic blood
      pressure (on-treatment isolated systolic hypertension) in treated hypertensive
      patients and identify the characteristics and treatment strategy in these
      patients. METHODS: Prospective cross-sectional survey in primary care.
      Participating physicians enrolled more than 13 consecutive treated hypertensive
      patients. Patients were considered to have isolated systolic hypertension when
      systolic blood pressure was at least 140 mmHg and diastolic blood pressure was
      less than 90 mmHg. RESULTS: On-treatment isolated systolic hypertension occurred
      in 28% of evaluable patients (n = 11562) and in 36% of uncontrolled patients (n =
      9080). Among the isolated systolic hypertension and among other uncontrolled
      patients, 53% and 47%, respectively, used more than one antihypertensive drug
      class. beta-Blockers were the most frequently prescribed antihypertensive drugs.
      Patients with isolated uncontrolled systolic blood pressure were more frequently
      treated with diuretics (43 vs. 39%) and angiotensin II receptor antagonists (23
      vs. 17%). Despite blood pressure being under control in only 21% of the patients,
      hypertension treatment was not changed in 46% of patients with isolated
      uncontrolled systolic blood presssure vs. 14% of patients with both uncontrolled
      systolic and diastolic blood pressure. CONCLUSION: In Belgium, the prevalence of
      on-treatment isolated systolic hypertension in treated hypertensive patients, was
      28%. The goal blood pressure was likely not reached in most patients due to
      inadequate treatment. The overall control rate was worse for systolic than for
      diastolic blood pressure. Furthermore, antihypertensive treatment was less
      frequently adapted in patients with isolated uncontrolled systolic blood pressure
      than in those patients with both uncontrolled systolic and diastolic blood
      pressure.

PMID- 18806632
TI  - Increased prevalence of metabolic syndrome in uncontrolled hypertension across
      Europe: the Global Cardiometabolic Risk Profile in Patients with hypertension
      disease survey.
AB  - OBJECTIVES: The Global Cardiometabolic Risk Profile in Patients with hypertension
      disease survey investigated the cardiometabolic risk profile in adult outpatients
      with hypertension in Europe according to the control of blood pressure (BP) as
      defined in the European Society of Hypertension and of the European Society of
      Cardiology (ESH/ESC) guidelines. METHODS: Data on BP control and cardiometabolic
      risk factors were collected for 3370 patients with hypertension in 12 European
      countries. Prevalence was analyzed according to BP status and ATP III criteria
      for metabolic syndrome. RESULTS: BP was controlled (BP < 140/90 mmHg for
      nondiabetic patients; BP < 130/80 mmHg for diabetic patients) in 28.1% of
      patients. Patients with uncontrolled BP had significantly higher mean weight,
      BMI, waist circumference, fasting blood glucose, total cholesterol and
      triglycerides and high-density lipoprotein cholesterol levels were significantly
      lower (women only) compared with patients with controlled BP (P < 0.05). The
      prevalence of metabolic syndrome and type 2 diabetes was also significantly
      higher in patients with uncontrolled BP compared with controlled BP (P < 0.001)
      (metabolic syndrome: 66.5 versus 35.5%; diabetes 41.1 versus 9.8%, respectively).
      95.3% of patients with both metabolic syndrome and type 2 diabetes had
      uncontrolled BP. In a multivariate analysis, diabetes and metabolic syndrome were
      found to be associated with a high risk of poor BP control: odds ratio, 2.56
      (metabolic syndrome); 5.16 (diabetes). CONCLUSION: In this European study, fewer
      than one third of treated hypertensive patients had controlled BP. Metabolic
      syndrome and diabetes were important characteristics associated with poor BP
      control. Thus, more focus is needed on controlling hypertension in people with
      high cardiometabolic risk and diabetes.

PMID- 18806633
TI  - Blood-pressure-related disease is a global health priority.

PMID- 18806634
TI  - A 21st-century nursing model: mutual recognition of nursing licenses.

PMID- 18806635
TI  - Public health emergency preparedness policy update.

PMID- 18806636
TI  - Standard 48: Administration set change.

PMID- 18806637
TI  - Typhilitis in the pediatric patient.
AB  - Cancer statistics in children are promising as mortality rates consistently
      decrease, reflecting newer chemotherapeutic agents and the evolution of
      hematopoietic stem cell transplant. Typhilitis or neutropenic enterocolitis is a
      potentially life-threatening complication of cancer treatment often found in
      immunocompromised children receiving vigorous chemotherapeutic regimens and noted
      in children post-stem-cell transplant. Recent literature suggests a relationship
      between typhilitis and other types of cancers and immunocompromised illness
      occurring in both children and adults. The pathogenesis of typhilitis is poorly
      understood, with limited evidence regarding incidence. Nursing care and
      assessment of children receiving oncologic treatment requires vigilance and
      immediate response to prevent and manage complications, especially
      gastrointestinally related typhilitis.

PMID- 18806638
TI  - Neonatal and pediatric perspectives in PICC placement.
AB  - The nurse providing care to the acute or critically ill child is all too familiar
      with the issues surrounding vascular access. Establishing and maintaining the
      correct access device is an ongoing problem. There are several types of vascular
      access devices available to the patient. Before placing any device, a thorough
      assessment of the patient is necessary. Choosing the wrong device can delay or
      interrupt the application of therapy. A peripherally inserted central catheter is
      one example of a vascular access device, and it is defined as a catheter inserted
      via a peripheral vein with the tip residing in the superior or inferior vena
      cava. This type of central catheter is commonly used in pediatric patients
      because it can offer reliable and stable vascular access. When appropriate,
      children with peripherally inserted central catheters can be discharged to the
      outpatient setting.

PMID- 18806639
TI  - The determination of record-keeping behavior of nurses regarding intravenous
      fluid treatment: the case of Turkey.
AB  - Record-keeping is one of the legal and professional responsibilities of nurses.
      This study aims to determine the record-keeping behavior of nurses regarding
      intravenous fluid treatment (IVFT). The study was conducted with 150 nurses
      working in adult clinics of a 936-bed university hospital. The most frequently
      fulfilled record-keeping behaviors were solution type, total solution amount, and
      date of treatment. The least frequent fulfilled behaviors were the diagnosis of
      patients and the time of passage of medication added to the solution. The nurses
      never recorded type of i.v. fluid treatment, complications, and discontinuation
      of therapy. According to findings of the study, the record-keeping behavior of
      nurses regarding IVFT is not at the desired level.

PMID- 18806640
TI  - A review of the pharmacology and pharmacotherapy of colony-stimulating factors.
AB  - Colony-stimulating factors (CSFs) have an established role in oncology. This
      article reviews the advances in the pharmacology, pharmacotherapy, and expanded
      indications of CSFs outside oncology and the role of the infusion nurse. New
      pharmacologic formulations of CSFs allow for less frequent dosing, less nursing
      administration time, and increased adherence. Expanded uses in human
      immunodeficiency virus/acquired immunodeficiency syndrome, Crohn's disease,
      mucositis, wound healing, chronic kidney disease, Jehovah's Witnesses, illegal
      use in sports, and non-drug-induced thrombocytopenia are reviewed. The role of
      the infusion nurse in the minimization of CSF prescribing errors, administration,
      monitoring, and patient education are summarized.

PMID- 18806642
TI  - The role of nursing in meeting the healthcare needs of diverse populations.

PMID- 18806643
TI  - Nurse-led interdisciplinary teams: challenges and rewards.

PMID- 18806645
TI  - Effect of patient-centered care on patient satisfaction and quality of care.
AB  - A clinical randomized study (posttest design) was conducted to examine whether
      patient-centered care (PCC) impacts patient satisfaction, perception of nursing
      care, and quality of care. Differences were seen in 2 of 3 subscales within the
      Baker and Taylor Measurement Scale. The PCC group rated satisfaction (P = .04)
      and quality of services (P = .03) higher than controls. PCC may impact patients'
      perception of the level of satisfaction and quality of care received.

PMID- 18806646
TI  - Use of the acute confusion protocol: a research utilization project.
AB  - This evidence-based project was undertaken to implement research-based preventive
      protocols to decrease the negative outcomes associated with delirium/acute
      confusion. After implementation, the medical-surgical unit experienced a 62%
      reduction in falls and a 100% decrease in sitter usage the first year. The use of
      medications known to cause acute confusion was decreased by more than 50%. Since
      implementation, the fall rate as well as the use of restraints has decreased by
      25%.

PMID- 18806647
TI  - Factors associated with reporting of medication errors by Israeli nurses.
AB  - This study investigated medication error reporting among Israeli nurses, the
      relationship between nurses' personal views about error reporting, and the impact
      of the safety culture of the ward and hospital on this reporting. Nurses (n =
      201) completed a questionnaire related to different aspects of error reporting
      (frequency, organizational norms of dealing with errors, and personal views on
      reporting). The higher the error frequency, the more errors went unreported. If
      the ward nurse manager corrected errors on the ward, error self-reporting
      decreased significantly. Ward nurse managers have to provide good role models.

PMID- 18806648
TI  - Overcoming barriers to research in a Magnet community hospital.
AB  - This study describes barriers perceived by nurses to the implementation of
      research findings in a community hospital. The BARRIERS to Research Utilization
      Scale was distributed to 1100 registered nurses. Items related to characteristics
      of the organization, including lack of time and practice authority, were
      perceived as the greatest barriers. Results of this study are useful for
      determining strategies to facilitate clinical nursing research and integrate
      research findings in the practice setting.

PMID- 18806649
TI  - Survival and quality of life following elective open-heart surgery.
AB  - Eight hundred thirty-six patients who had open-heart surgery were available for
      analysis of health-related quality of life (HRQL) data and survival at the 1-year
      follow-up. Elective open-heart surgery patients with decreasing HRQL at 1 year
      following surgery may experience a survival disadvantage in comparison with those
      patients experiencing positive gains. Clinical care should extend beyond the
      immediate postoperative period.

PMID- 18806650
TI  - Critical care nurses' perceptions of patient safety in Turkey.
AB  - This study explored 150 critical care nurses' perceptions of patient safety
      standards in a selection of private, public, and university hospitals in Turkey.
      Quality management and patient safety programs were more prevalent in private
      hospitals. Private hospitals were also more likely to encourage reporting, have
      error/adverse event reporting systems, and less likely to have a punitive
      response to reported errors. However, respondents who work in private hospitals
      work both more hours per week and more hours per day.

PMID- 18806651
TI  - Biologic response modifiers for ophthalmologists.

PMID- 18806652
TI  - Transient descent of the contralateral eyelid in unilateral ptosis surgery.
AB  - PURPOSE: To report novel findings regarding contralateral eyelid height (i.e.,
      intraoperative descent, followed by postoperative elevation) during unilateral
      ptosis surgery and to comment on their relevance in surgical planning. METHODS:
      Twelve adults with unilateral ptosis underwent levator advancement surgery.
      During surgery, eyelid height was set to the contralateral preoperative margin
      reflex distance value, rather than intraoperative level. The margin reflex
      distance of both eyes was measured before, during, and after surgery. RESULTS:
      The mean preoperative margin reflex distance on the ptotic side was 0.63 mm
      versus 3.83 mm contralaterally. No patient demonstrated a Hering phenomenon
      preoperatively. In each case, the goal was to elevate the ptotic eyelid to the
      contralateral preoperative height. For the ptotic eyelid, this resulted in a mean
      intraoperative margin reflex distance of 4 mm. Simultaneously, the contralateral
      side was noted to drop in each case, to a mean margin reflex distance of 1.67 mm.
      Postoperatively, at a mean follow up of 1.25 weeks, the mean margin reflex
      distance values were 3.88 mm and 3.83 mm for the operated and unoperated sides,
      respectively (Pearson correlation coefficient = 0.88, p < 0.05). At a mean follow
      up of 4.35 months, the mean margin reflex distance values were 3.80 mm and 3.83
      mm for the operated and unoperated sides, respectively (Pearson correlation
      coefficient = 0.96, p < 0.05). No patient had greater than 0.5 mm of asymmetry,
      and no patient requested postoperative adjustment. Had intraoperative symmetry
      been obtained with a postoperative contralateral return to preoperative height, a
      mean 42.1% of postoperative height asymmetry would have resulted between the 2
      eyelids. CONCLUSIONS: During unilateral levator advancement surgery, the authors
      noted that the contralateral eyelid temporarily droops, and this Hering-like
      effect reverses postoperatively. The authors recommend that by raising the
      operated eyelid to the height of the contralateral side's preoperative (rather
      than intraoperative) height, excellent postoperative eyelid height and symmetry
      can be obtained.

PMID- 18806653
TI  - Reconstruction of the tarsus-conjunctival layer using a venous wall graft.
AB  - PURPOSE: The repair of full-thickness defects of the eyelids poses a challenge,
      because the reconstruction of the tarsus-conjunctival layer often results in
      aesthetically and functionally unsatisfactory outcomes. The authors' aim was to
      create a new method to repair large tarsus-conjunctival losses and to examine the
      outcomes of its use. METHODS: Seven patients with invasive carcinoma of the
      eyelids underwent a venous wall graft. RESULTS: All patients had good to
      outstanding results and no complications. CONCLUSION: This new reconstruction of
      the deeper layer of the eyelid provides a useful alternative to traditional
      methods (composite grafts and full-thickness flaps). Our new surgical technique
      is easy to execute and has good functional and aesthetic results.

PMID- 18806654
TI  - Intratarsal epidermal inclusion cyst.
AB  - PURPOSE: To report 3 cases of epidermal inclusion cyst that arose within the
      tarsus, an unusual site of origin. METHODS: A retrospective review of medical
      records of patients undergoing excision of eyelid epidermal inclusion cysts by
      one surgeon (MJL) over a decade revealed 3 cases of intratarsal epidermal
      inclusion cyst. Initially, these lesions resembled chalazia and were first
      addressed with incision and curettage. There was recurrence of the cyst in all
      the 3 cases from 1 to 4 months, and subsequent complete excision was necessary.
      RESULTS: At surgery in each of these cases a cyst arising within the tarsus was
      encountered. Eventually, the tarsus containing the base of the cyst was excised
      to ensure complete removal. The cysts were approximately 8 mm to 10 mm in
      greatest dimension and had yellowish-white gelatinous contents. Histopathologic
      evaluation revealed keratin-filled cysts arising from tarsus and lined by
      stratified keratinized epithelium. In one of the cases the tarsal tissue around
      the cyst wall showed epidermal elements presumably derived from sebaceous gland.
      There have been no recurrences after complete excision (follow-up range, 9-60
      months). CONCLUSIONS: Intratarsal epidermal inclusion cysts share some clinical
      features with chalazia. Lack of inflammation, lack of fluctuation in size,
      gradual continued slow growth, and delayed onset of recurrence may help to
      differentiate tarsal cyst from recurrent chalazion. Incision and curettage,
      however, is not effective long-term treatment for this entity. Total excision of
      the cyst including full-thickness excision of tarsus at the cyst's base of origin
      is suggested for definitive treatment.

PMID- 18806655
TI  - Human orbital sympathetic nerve pathways.
AB  - PURPOSE: To determine pathways of sympathetic nerves from the orbital apex to the
      eyelids in human cadaver tissue using immunohistochemistry. METHODS: Human
      cadaver orbit tissue was sectioned and immunolabeled with a monoclonal
      antityrosine hydroxylase antibody. RESULTS: In the orbital apex, the nasociliary,
      frontal, lacrimal, and maxillary branches of the trigeminal nerve demonstrated
      intense staining upon entering the orbit. Immunoreactive axons from the
      nasociliary and frontal nerves were observed to join the extraocular motor nerves
      in the posterior orbit. A plexus of immunolabeled nerves was observed to
      accompany the ophthalmic artery as it entered the orbital apex. The ophthalmic
      artery and its branches throughout the orbit demonstrated staining of nerve
      fibers in the peripheral muscularis. The nasociliary nerve contributed
      sympathetic branches to the ciliary ganglion. Nerves passing through the ciliary
      ganglion and a few ganglion cell bodies demonstrated mild to moderate tyrosine
      hydroxylase reactivity. Axons within the short and long ciliary nerves
      demonstrated strong tyrosine hydroxylase reactivity and were observed to enter
      the posterior sclera and the suprachoroidal space. The lacrimal gland
      demonstrated mild pericapillary staining and occasional stromal nerve fibers
      reactive to the antityrosine hydroxylase antibody. Muller muscle and the inferior
      tarsal muscle possessed a strong tyrosine hydroxylase-reactive nerve supply that
      appeared to originate from the anterior terminal branches of the nasociliary and
      lacrimal nerves. CONCLUSIONS: Sympathetic nerves enter the orbit via the first
      and second divisions of the trigeminal nerve and a plexus of nerves surrounding
      the ophthalmic artery. Extraocular motor nerves receive a sympathetic nerve
      supply from the sensory nerves in the posterior orbit. Some ciliary ganglion cell
      bodies demonstrated tyrosine hydroxylase-like reactivity, suggesting a
      sympathetic modulatory role for the ciliary ganglion. Sympathetics innervate
      ocular structures via the posterior ciliary nerves. Sympathetic axons travel
      anteriorly in the orbit via the nasociliary and lacrimal nerves to innervate the
      sympathetic eyelid muscles. Sympathetic nerves also travel with the frontal
      branch of the ophthalmic nerve to innervate the forehead skin. The ophthalmic
      artery and all of its branches contain a perivascular sympathetic nerve supply
      that may be involved in regulation of blood flow to ocular and orbital
      structures.

PMID- 18806656
TI  - Intraorbital polyacrylamide gel injection for the treatment of anophthalmic
      enophthalmos.
AB  - PURPOSE: To evaluate the use of orbital polyacrylamide gel injection for the
      correction of anophthalmic enophthalmos. METHODS: Noncontrolled clinical trial of
      21 patients (14 with ocular implants, 5 with phthisis bulbi, and 2 with dermis
      fat graft). Orbital CT was performed to estimate the volume of polyacrylamide gel
      needed to restore orbital volume. Polyacrylamide gel was injected using a 22
      gauge (30 x 0.7 mm) needle transcutaneously inserted in the lateral third of the
      lower eyelid, directed to the orbital muscle cone. A second injection was
      administered 15 days later, if necessary. CT was repeated 30 days after the last
      procedure. Exophthalmometry was performed before and 90 days after the procedure.
      RESULTS: The mean total volume injected per orbit was 2.4 +/- 0.7 ml (range, 1
      3.5 ml). The volume of the enophthalmic orbit increased from 26.9 +/- 5.0 ml to
      29.3 +/- 4.9 ml (p < 0.001). The mean difference in exophthalmometry readings was
      3.3 +/- 1.6 mm (range, 1.5-8.0 mm) before the procedure and 1.0 +/- 0.9 mm
      (range, 0.0-3.0 mm) after 3 months (p < 0.001). Adjustment of the ocular
      prosthesis or fabrication of a new one was necessary in 11 patients (52.4%), and
      the mean volume of the ocular prosthesis was reduced from 2.0 +/- 0.6 ml to 1.6
      +/- 0.6 ml (p = 0.003). All patients were satisfied with the aesthetic results.
      No serious adverse events were observed. The initial results were maintained 1
      year after the procedure. CONCLUSIONS: Polyacrylamide gel injection in the
      orbital space effectively reduces enophthalmos in ocular prosthesis wearers.

PMID- 18806657
TI  - Intraoperative predictability of temporal artery biopsy results.
AB  - PURPOSE: To determine whether inflammatory/granulomatous changes of giant cell
      arteritis can be grossly identified by the surgeon during temporal artery biopsy
      to allow institution or discontinuation of steroid therapy without delay.
      METHODS: The records of 113 consecutive patients operated on by the same surgeon
      (R.C.K.) between November 2002 and June 2007 were reviewed. Demographic
      characteristics, date and site of the surgeries, surgical complications,
      surgeon's intraoperative presumption about the outcome (based on his assessment
      of the thickness, nodularity, tortuosity, and color/pallor of the arterial wall,
      blood flow, and the lumen size), and histopathologic biopsy results were
      collected from the chart review. The main outcome measure was the correspondence
      of the surgeon's intraoperative impression expressed in the operative note to the
      ultimate histopathologic diagnosis. RESULTS: After exclusion of 5 cases with
      incomplete data, the study consisted of 108 patients (78 females and 30 males)
      with an average age of 72.4 +/- 11.4 years (range, 45-93 years). There were no
      complications during or after surgery. The surgeon's comment was "grossly
      positive" in 17 cases, and 15 of these cases were pathologically positive. For
      all of the cases that the surgeon's impression was negative, the pathology was
      negative as well (100% negative predictive value). Overall, the surgeon's
      intraoperative comments had a 100% sensitivity to detect giant cell arteritis.
      The specificity and accuracy values were 97.9% and 98.2%, respectively.
      CONCLUSION: The surgeon's intraoperative evaluation of the temporal artery may be
      extremely valuable in predicting the biopsy result and may allow the surgeon to
      determine whether steroids could be discontinued in patients in whom the clinical
      history is not highly suggestive of giant cell arteritis.

PMID- 18806659
TI  - Orbital hyperostosis following exenteration.
AB  - PURPOSE: To report the development of unilateral, diffuse hyperostosis of orbital
      bones in 3 postexenteration patients. METHODS: Three advanced cases of
      periorbital and orbital malignancies are presented, and their clinical,
      radiologic, and histopathologic features are reviewed. RESULTS: Postexenteration
      CT showed thickened orbital walls in all 3 cases. The histopathology revealed
      necrotic destruction of the trabeculae mixed with randomly distributed chronic
      inflammatory cells and fibrosis and inflamed overlying granulation tissue.
      CONCLUSION: The delayed healing of the granulation tissue during secondary
      intention in these cases is quite likely the cause of chronic osteitis of the
      underlying orbital bone that, in turn, led to postoperative diffuse hyperostosis.

PMID- 18806660
TI  - Computer-aided volume measurement of posttraumatic orbits reconstructed with AO
      titanium mesh plates: accuracy and reliability.
AB  - PURPOSE: To prospectively evaluate the accuracy and reliability of "freehand"
      posttraumatic orbital wall reconstruction with AO (Arbeitsgemeinschaft
      Osteosynthese) titanium mesh plates by using computer-aided volumetric
      measurement of the bony orbits. METHODS: Bony orbital volume was measured in 12
      patients from coronal CT scan slices using OsiriX Medical Image software. After
      defining the volumetric limits of the orbit, the segmentation of the bony orbital
      region of interest of each single slice was performed. At the end of the
      segmentation process, all regions of interest were grouped and the volume was
      computed. The same procedure was performed on both orbits, and thereafter the
      volume of the contralateral uninjured orbit was used as a control for comparison.
      RESULTS: In all patients, the volume data of the reconstructed orbit fitted that
      of the contralateral uninjured orbit with accuracy to within 1.85 cm3 (7%).
      CONCLUSIONS: This preliminary study has demonstrated that posttraumatic orbital
      wall reconstruction using "freehand" bending and placement of AO titanium mesh
      plates results in a high success rate in re-establishing preoperative bony
      volume, which closely approximates that of the contralateral uninjured orbit.

PMID- 18806661
TI  - Nonlaser endoscopic endonasal dacryocystorhinostomy with adjunctive mitomycin C
      in children.
AB  - PURPOSE: To determine the outcome and safety of pediatric endonasal
      dacryocystorhinostomy with the use of adjunctive mitomycin C. METHODS: A
      prospective, nonrandomized and noncomparative interventional case series study
      was performed in 71 consecutive procedures. Sixty patients 16 years of age and
      younger underwent nonlaser endonasal dacryocystorhinostomy with the use of
      adjunctive mitomycin C. Eleven patients had a simultaneous bilateral procedure
      performed. All patients underwent a standardized procedure, with an endonasal
      approach to the lacrimal sac and surgical removal of nasal mucosa, lacrimal bone,
      and a fragment of the frontal process of the maxilla. The medial wall of the
      lacrimal sac was completely removed and a neurosurgical cottonoid soaked in
      mitomycin C at 0.5 mg/ml placed at the osteotomy site for 5 minutes. All patients
      underwent bicanalicular or monocanalicular silicone intubation. RESULTS: The main
      outcome measures were the resolution of epiphora, lacrimal discharge, and patency
      of the ostium confirmed either by endoscopic visualization and/or irrigation at 6
      months or a normal dye disappearance test. Thirteen patients' (18%) final
      evaluation was via telephone survey. The mean follow-up was 12.3 months. Nonlaser
      endonasal dacryocystorhinostomy with adjunctive mitomycin C was successful in 67
      cases (94.4%). African descent was strongly associated with a higher rate of
      obstruction (p < 0.001). Infection at the time of surgery (p = 0.051) and less
      than 3 months intubation (p = 0.059) were also borderline significant. Previous
      trauma, gender, age, and side operated had no influence on the final outcome. No
      significant complications were encountered. CONCLUSIONS: Nonlaser endonasal
      dacryocystorhinostomy with mitomycin C is a safe and successful procedure for the
      treatment of congenital nasolacrimal duct obstruction in children. It has the
      advantage of leaving no scar and of preserving the medial canthal structures. It
      can be successfully performed as a simultaneous bilateral procedure.

PMID- 18806662
TI  - Pathogenesis of canalicular lacerations.
AB  - PURPOSE: To assess the pathogenesis of canalicular lacerations. METHODS: This is
      a retrospective, clinical case series of 236 patients who sustained a canalicular
      laceration. All patients who presented to the oculoplastic service of 3
      individuals (D.R.J., S.M.G., L.A.M.) from May 1, 1998 to September 30, 2007, with
      a canalicular laceration were included in the study. Case histories were
      carefully reviewed in an attempt to classify the mechanism of injury as: "direct
      (penetrating) injury," "indirect (avulsive)," or "diffuse (avulsive)." Associated
      injuries (floor fractures, soft tissue lacerations, etc.) were also recorded.
      RESULTS: Of the 236 patients reviewed, direct canalicular injuries were detected
      in 128 (54.2%), indirect injuries were detected in 60 (25.4%), and diffuse
      injuries were detected in 48 (20.3%). Avulsive blunt injuries (due to indirect or
      diffuse trauma) therefore accounted for 45.7% of the lacerations whereas direct
      penetrating injuries accounted for 55.2% of the canalicular lacerations. Other
      injuries associated with the trauma occurred in 152 of the 236 patients (64%).
      Lacerations involving other portions of the eyelids, periocular area, and face
      made up the greatest number of associated injuries, and occurred with equal
      frequency in the direct penetrating group and the indirect/diffuse (avulsive
      injury) group. Associated injuries more serious in nature including orbital
      fractures, globe rupture, other body injuries, and head trauma were more commonly
      seen when diffuse trauma was involved. CONCLUSIONS: Direct, indirect, or diffuse
      forces may injure canaliculi but direct penetrating injuries were more common
      than avulsive injuries. More serious injuries (orbital fractures, globe rupture,
      other body injuries, and head trauma) were more commonly seen when diffuse trauma
      was involved.

PMID- 18806663
TI  - Long-term success rate of perforated punctal plugs in the management of acquired
      punctal stenosis.
AB  - PURPOSE: To give the long-term success rates of punctal dilatation with insertion
      of perforated punctal plugs (PPP) for the management of acquired punctal
      stenosis. METHODS: A series of 44 eyes of 26 patients who underwent PPP
      implantation for the management of acquired punctal stenosis were retrospectively
      evaluated in terms of the severity of acquired punctal stenosis, associated
      eyelid disorders, implantation technique of PPP, and long-term success rate of
      PPP for the treatment of epiphora. In all patients, punctal dilation was
      performed prior to the insertion of plugs. Patients demonstrating moderate or
      severe horizontal eyelid laxity underwent a lateral tarsal strip procedure before
      PPP implantation. Complete stenosis of the punctum was treated with the
      radiofrequency unit before PPP implantation. The plugs were extracted at 2 months
      in every patient. RESULTS: The mean age of the patients was 63.6 +/- 10.5 years.
      The median interval between the onset of epiphora and PPP implantation was 15
      months. There were 14 complete stenoses, 29 partial punctal stenoses, and 1
      squamous papilloma involving the inferior punctum causing epiphora. Associated
      eyelid laxity was detected in 14 of 44 eyes (31.8%), and 8 eyes underwent a
      lateral tarsal strip procedure before PPP implantation. The mean follow-up time
      was 19.0 +/- 13.4 months. Success was achieved in 37 of 44 eyes (84.1%), with
      relief of epiphora. Of the 7 eyes with continued epiphora, 3 eyes demonstrated
      recurrent punctal stenosis and 4 eyes demonstrated mild horizontal eyelid laxity.
      CONCLUSIONS: The long-term success rate of PPP implantation for the treatment of
      acquired punctal stenosis is satisfactory. Associated eyelid pathologies should
      be evaluated for their contribution to epiphora and be treated before PPP
      implantation.

PMID- 18806664
TI  - Medial canthal tophus.
AB  - A 68-year-old-man was seen in consultation for a suspicious medial canthal lesion
      that developed over a 2-year period. The raised, nodular lesion was skin colored,
      had a raised pearly border and a central depression with superficial crusting.
      Basal cell carcinoma was suspected and an excisional biopsy was performed.
      However, a granulomatous inflammatory process with features consistent with gout
      was identified. Further inquiry confirmed a history of gout including prior tophi
      on each elbow. Gouty tophi are extremely rare in the periocular area but should
      be considered in the differential diagnosis of basal cell carcinoma as they may
      have a similar clinical appearance.

PMID- 18806665
TI  - Gouty tophus of the upper eyelid.
AB  - A 64-year-old man with gout presented with history of an enlarging mass in the
      left upper eyelid causing mechanical ptosis. The patient underwent excisional
      biopsy. The histopathologic findings confirmed the diagnosis of gouty tophus of
      the eyelid.

PMID- 18806666
TI  - Autologous serum eye drops used to treat an ulcerated dermis-fat graft.
AB  - A 49-year-old woman with a contracted and keratinized anophthalmic socket
      underwent a dermis-fat graft for orbital augmentation. She presented with an
      early ulcer on the surface of the dermis, with inhibited conjunctival growth.
      There was no improvement after 1 month of conservative treatment. The authors
      applied autologous serum eye drops to accelerate epithelial repair, with
      resolution of the ulcer and reduction of surface keratin within 3 weeks. This is
      the first report of dermis-fat graft ulcer treated with autologous serum.

PMID- 18806667
TI  - Bilateral intraorbital abscesses and cavernous sinus thromboses secondary to
      Streptococcus milleri with a favorable outcome.
AB  - A 51-year-old woman with left proptosis, diplopia, headache, and nausea was found
      to have bilateral intraorbital abscesses, left superior ophthalmic vein
      thrombosis, bilateral cavernous sinus thromboses, and a left temporal lobe
      intracerebral abscess. Because the paranasal sinuses were unaffected, a dental
      origin was suspected and confirmed. The causative organism was Streptococcus
      milleri. Aggressive surgical intervention included bilateral orbital abscess
      drainage and dental extraction, and medical therapy included intravenous
      metronidazole, ceftriaxone, heparin, and methylprednisolone. A left sixth cranial
      nerve paresis was the only long-term sequela.

PMID- 18806668
TI  - Chronic orbital inflammation and fibrosis after retrobulbar alcohol and
      chlorpromazine injections in a patient with choroidal melanoma.
AB  - A 59-year-old woman developed a choroidal melanoma in her right eye and was
      successfully treated with plaque radiotherapy in 1995. She subsequently developed
      a blind, painful eye and was treated with retrobulbar alcohol and chlorpromazine
      injections. A transient acute severe inflammatory reaction to chlorpromazine was
      noted, and chronic pain persisted. MRI performed 5 months later revealed diffuse
      orbital enhancement suggestive of either fibrosis or tumor recurrence. Following
      enucleation, diffuse orbital fibrosis was confirmed. The unusual fibrosis could
      have been related to the orbital injections or remotely related to long-term
      effects of radiotherapy.

PMID- 18806669
TI  - Botulinum toxin as novel treatment for excess mucous membrane graft secretions.
AB  - Salivary gland secretion is an unusual complication of mucous membrane grafting.
      The authors report a case in which botulinum toxin was successfully used to treat
      graft secretions after buccal mucous membrane autograft for recurrent pterygium
      repair.

PMID- 18806670
TI  - Malignant peripheral nerve sheath tumor of the orbit: malignant transformation
      from neurofibroma without neurofibromatosis.
AB  - A 52-year-old woman suffered from progressive proptosis and vision loss due to a
      large tumor in her right orbit. Multiple recurrences of the tumor were treated
      with surgical excision. The pathologic diagnosis in each recurrence was
      neurofibroma, and the tumor transformed to malignant peripheral nerve sheath
      tumor in the final pathologic diagnosis. Orbital exenteration and postoperative
      irradiation were applied and there has been no evidence of tumor recurrence 5
      years postoperatively.

PMID- 18806671
TI  - Successful treatment of idiopathic orbital inflammation with infliximab: an
      alternative to conventional steroid-sparing agents.
AB  - Therapy for orbital pseudotumor, also called idiopathic orbital inflammation, is
      nonspecific and mainly based on the use of corticosteroids. Two patients with
      steroid-dependent idiopathic orbital inflammation, one with myositis and the
      other with dacryoadenitis, and intolerant of standard steroid sparing agents
      (methotrexate or azathioprine), were treated with infliximab, a monoclonal
      antitumor necrosis factor alpha antibody. In both patients, orbital
      manifestations disappeared following treatment. After follow-up for at least 20
      months, the 2 patients still receiving infliximab remained event free. Infliximab
      enabled steroid tapering to less than 5 mg per day, suggesting that infliximab
      could constitute an alternative to conventional steroid sparing agents.

PMID- 18806672
TI  - Primary localized conjunctival amyloidosis simulating a lymphoproliferative
      disorder.
AB  - A 39-year-old previously healthy woman presented with a 3-year history of a
      painless lump in her left upper eyelid that had been increasing in size over the
      last 8 months. On examination, a soft, nontender mass was palpated in the medial
      left upper eyelid and anterior orbit. She had 2 mm of eyelid ptosis and 2 mm of
      inferior globe displacement. A salmon-pink mass of tissue was identified in the
      superomedial conjunctiva. The remaining ophthalmic examination was unremarkable.
      A lymphoproliferative process was suspected; however, an incisional biopsy
      revealed amyloid. Further workup showed no evidence of systemic amyloidosis,
      lymphoma, plasmacytoma, or multiple myeloma. The patient has been followed for
      more than 16 months with no new developments in her health. Amyloidosis has a
      variety of presentations in the periocular region and may be the sole
      manifestation of the disease process. It is not often considered in the
      differential diagnosis of conjunctival lesions. The classic "salmon-pink"
      conjunctival infitrate has been associated with lymphoproliferative disorders;
      however, amyloid should also be considered, as it may be clinically
      indistinguishable.

PMID- 18806673
TI  - Anetodermic variant of a periorbital pilomatricoma.
AB  - Pilomatricoma usually presents as a solitary hard nodule located deep in the
      dermis. However, a variant termed anetodermic is often seen in the elderly.
      Instead of a hard nodule, a rapidly growing bullous lesion is seen. The authors
      report a 60-year-old man who presented with an erythematous bullous lesion at the
      left medial canthus. The lesion started as a small 3-mm papule and grew
      significantly to a 12-mm lesion in 5 weeks. Histopathologically, the tumor was
      composed of basophilic and keratinized shadow cells typical of pilomatricoma.
      Anetodermic changes could also be seen, represented by intralesional hemorrhage,
      dilated blood and lymphatic vessels, and disruption of dermal collagen fibers.
      The anetodermic variant of pilomatricoma was described in 1943 and accounts for
      only 2% of cases. Compression of vessels by the neoplastic process and
      peritumoral inflammatory infiltration are the proposed pathogenic mechanisms
      underlying the atypical findings.

PMID- 18806674
TI  - Eyelid mass secondary to injection of calcium hydroxylapatite facial filler.
AB  - A 37-year-old woman presented with a 2-month history of fullness and ptosis of
      the left upper eyelid. Examination revealed a 6-cm x 2-cm mass in the left brow
      and upper eyelid, and a diffuse mass in the lower eyelid. Marked ptosis of the
      left upper eyelid and elevation of the left lower eyelid were noted. CT showed
      masses with a bone-like density in the left eyelid and periorbital soft tissue. A
      through history revealed that the patient had received calcium hydroxylapatite
      filler injection for nose augmentation 3 days prior to the development of the
      eyelid masses. The eyelid masses were excised and pathologically confirmed as
      calcium hydroxylapatite microspherules surrounded by collagen and histiocytes.
      Two months after surgery, the eyelid masses and ptosis of the left upper eyelid
      were completely resolved. To our knowledge, this is the first reported case of
      eyelid mass after injection of calcium hydroxylapatite facial filler for nose
      augmentation.

PMID- 18806675
TI  - Fibrous dysplasia-like tumor of the lacrimal sac.
AB  - A 75-year-old woman developed epiphora and a slowly enlarging right medial
      canthal mass for 1 year. CT revealed a mass with ground-glass radiodensity and
      hazy borders in the lacrimal sac. At external dacryocystorhinostomy, a tan,
      gritty, spherical mass was easily removed from the sac lumen. Histopathologic
      characteristics were typical of fibrous dysplasia. The postoperative course was
      uneventful.

PMID- 18806676
TI  - Posttraumatic cellulitis and ulcerative conjunctivitis caused by Yersinia
      enterocolitica O:8.
AB  - A 55-year-old white man presented with orbital cellulitis and suspicion of an
      intraorbital foreign body after ocular trauma. He underwent orbital exploration,
      but no intraorbital foreign bodies were identified. Intraoperative orbital and
      conjunctival cultures grew Yersinia enterocolitica O:8. The patient's signs and
      symptoms resolved with intravenous antibiotic treatment after this exploratory
      orbitotomy. This is the first case, to our knowledge, of human orbital cellulitis
      caused by Y. enterocolitica O:8. The single visible interpalpebral conjunctival
      ulceration was suspected to be an entry wound by the patient's primary physician,
      the emergency room physician, and the orbital surgeon prior to surgical
      investigation, at which time all the other ulcerations were identified.
      Therefore, the physical manifestations of this rare but important infection are
      presented because they may mislead clinicians in suspecting an intraorbital
      foreign body.

PMID- 18806677
TI  - The levator aponeurosis exposed.
AB  - A case of bilateral upper eyelid ptosis in an HIV-infected patient with severe
      antiretroviral-associated facial lipodystrophy is presented. The features,
      treatment, and outcome are discussed. Dehiscence of the levator aponeurosis may
      be directly associated with highly active antiretroviral therapy-induced
      lipodystrophy.

PMID- 18806678
TI  - Ampulla of the lower lacrimal canaliculus: does it exist?

PMID- 18806679
TI  - Low-cost headlamps for facial and oculoplastic surgery.

PMID- 18806681
TI  - Re: "Simultaneous eyelid and choroidal metastases 36 years after diagnosis of
      medullary thyroid carcinoma".

PMID- 18806683
TI  - Re: "Correction of anophthalmic enophthalmos with injectable calcium
      hydroxylapatite (Radiesse)".

PMID- 18806685
TI  - Re: "Medial pretarsal adipose tissue in the Asian upper eyelid".

PMID- 18806686
TI  - Effects of the route of estrogen administration on insulinlike growth factor-I,
      IGF binding protein-3, and insulin resistance in healthy postmenopausal women:
      results from a randomized, controlled study.
AB  - OBJECTIVE: Oral estrogen therapy suppresses insulin like growth factor I (IGF-I)
      levels, whereas conventional dose transdermal estradiol (E2) does not. However,
      it has been proposed that if sufficiently high serum E2 levels are achieved,
      nonoral E2 will also suppress serum IGF-I. The aim of the study was to
      investigate the effects of intranasal E2 with norethisterone (E2/NET) versus oral
      E2/NET acetate on IGF-I, IGF binding protein 3, and insulin resistance in
      postmenopausal women. DESIGN: This was a randomized, multicenter, double-blind,
      double-dummy trial. Postmenopausal women were randomized to receive either daily
      intranasal E2/NET (175 microg/275 microg) as a spray and a placebo tablet (n =
      41) or oral E2/NET acetate (1 mg/0.5 mg) plus placebo intranasal spray (n = 41)
      for 1 year. Fasting plasma concentrations of IGF-I, IGF binding protein 3,
      glucose and insulin, glucose and insulin at 120 minutes post-glucose challenge,
      and the homeostasis model assessment for insulin resistance were assessed at
      baseline and after 52 weeks of treatment. RESULTS: The two groups were well
      matched for all clinical and biochemical parameters at baseline. There were no
      significant between-group differences for fasting and 120-minute glucose,
      insulin, homeostasis model assessment for insulin resistance, and IGF binding
      protein 3. The mean IGF-I level at week 52 was significantly lower for women
      treated with oral versus intranasal therapy (116 +/- 21 [SD] versus 134 +/- 33
      [SD], P = 0.005) and the mean difference in change over 52 weeks in IGF-I was
      significantly different between groups (-19, 95% CI:-37 to -1, P = 0.04).
      CONCLUSIONS: In healthy postmenopausal women, intranasal E2 at a dose that
      results in serum levels that exceed the proposed threshold for growth hormone and
      IGF-I effects, does not alter IGF-I levels. This suggests that the effect of
      exogenous estrogen on IGF-I is a function of the method of administration rather
      than being dose related.

PMID- 18806687
TI  - Both frequency and interaural delay affect event-related potential responses to
      binaural gap.
AB  - Human listeners are extraordinarily sensitive to a transient break in interaural
      correlation (called binaural gap). In this study, a binaural gap embedded in
      interaurally correlated noise markers elicited marked scalp event-related
      potentials (ERPs). ERPs to the binaural gap in narrowband noise with the center
      frequency of 1600 Hz were significantly weaker than those for narrowband noise
      with the center frequency of 400 or 800 Hz. Introducing the interaural time
      difference (ITD) of 4 ms weakened the ERPs for either 400-Hz or 800-Hz noise.
      Introducing the ITD of 2 ms, however, only weakened the ERPs for 800-Hz but not
      400-Hz noise. Thus central representations of a transient break in interaural
      correlation for narrowband noises are affected by both frequency and ITD.

PMID- 18806689
TI  - Attention-related modulation of auditory brainstem responses during contralateral
      noise exposure.
AB  - As determinants facilitating attention-related modulation of the auditory
      brainstem response (ABR), two experimental factors were examined: (i) auditory
      discrimination; and (ii) contralateral masking intensity. Tone pips at 80 dB
      sound pressure level were presented to the left ear via either single-tone
      exposures or oddball exposures, whereas white noise was delivered continuously to
      the right ear at variable intensities (none--80 dB sound pressure level).
      Participants each conducted two tasks during stimulation, either reading a book
      (ignoring task) or detecting target tones (attentive task). Task-related
      modulation within the ABR range was found only during oddball exposures at
      contralateral masking intensities greater than or equal to 60 dB. Attention
      related modulation of ABR can thus be detected reliably during auditory
      discrimination under contralateral masking of sufficient intensity.

PMID- 18806688
TI  - Splenium microstructure is related to two dimensions of reading skill.
AB  - Inconsistent differences in the corpus callosum (CC) structure between dyslexic
      readers (DRs) and typical readers (TRs) have been reported. We examine
      differences in CC splenium microstructure and the association of splenium
      microstructure with reading-related skills. Nine DRs and 18 TRs completed a
      reading skills battery and diffusion tensor imaging. DRs had higher splenium
      fractional anisotropy (FA) and axial diffusivity (LA) as compared with TRs.
      Retrieval of orthographic information from the language lexicon was negatively
      associated with FA and LA within both reading groups. Phonological awareness was
      positively associated with splenium FA and LA in TRs but not DRs. This study
      suggests two white matter pathways that may be differentially associated with
      reading skills in the CC splenium.

PMID- 18806690
TI  - Time-dependent changes in striatal xCT protein expression in hemi-Parkinson rats.
AB  - Altered glutamate signaling is associated with Parkinson's disease. To study the
      involvement of the cystine/glutamate antiporter in the pathogenesis of
      Parkinson's disease, we developed new polyclonal antibodies recognizing xCT, the
      specific subunit of this antiporter. The striatal xCT protein expression level
      was investigated in a hemi-Parkinson rat model, using semiquantitative western
      blotting. We observed time-dependent changes after a unilateral 6-hydroxydopamine
      lesion of the nigrostriatal pathway with increased expression levels in the
      deafferented striatum after 3 weeks. Twelve weeks postlesion, expression levels
      returned to normal. These data suggest, for the first time, an involvement of the
      cystine/glutamate antiporter in determining the aberrant glutamate
      neurotransmission in the striatum of a parkinsonian brain.

PMID- 18806691
TI  - Mapping cerebellar degeneration in HIV/AIDS.
AB  - Progressive brain atrophy in HIV/AIDS is associated with impaired psychomotor
      performance, perhaps partly reflecting cerebellar degeneration; yet little is
      known about how HIV/AIDS affects the cerebellum. We visualized the three
      dimensional profile of atrophy in 19 HIV-positive patients (age: 42.9+/-8.3
      years) versus 15 healthy controls (age: 38.5+/-12.0 years). We localized
      consistent patterns of subregional atrophy with an image analysis method that
      automatically deforms each patient's scan, in three dimensions, to match a
      reference image. Atrophy was greatest in the posterior cerebellar vermis (14.9%
      deficit) and correlated with depression severity (P=0.009, corrected), but not
      with dementia, alcohol/substance abuse, CD4+T-cell counts, or viral load.
      Profound cerebellar deficits in HIV/AIDS (P=0.007, corrected) were associated
      with depression, suggesting a surrogate disease marker for antiretroviral trials.

PMID- 18806692
TI  - The 18-kDa translocator protein, formerly known as the peripheral-type
      benzodiazepine receptor, confers proapoptotic and antineoplastic effects in a
      human colorectal cancer cell line.
AB  - OBJECTIVE: The involvement of the 18-kDa translocator protein (TSPO), formerly
      known as the peripheral-type benzodiazepine receptor, in apoptosis regulation of
      HT29 colorectal cancer cells was studied in-vitro. In-vivo TSPO involvement in
      tumor growth of HT29 cells xenografted into SCID mice was studied. METHODS:
      Knockdown of TSPO expression in the human HT29 cell line was established by
      stable transfection with vectors containing the TSPO gene in the antisense
      direction. Successful TSPO knockdown was characterized by reduction of 20% in
      TSPO RNA levels, 50% in protein expression of the TSPO, and 50% in binding with
      the TSPO ligand, [3H]PK 11195. Subsequently, in-vitro cell viability and
      proliferation assays were applied. In addition, transient transfecton with short
      interfering RNA (siRNA) directed against human TSPO was studied in this way.
      Furthermore, we also grafted HT29 cells subcutaneously into the right thighs of
      SCID mice to examine the effects of the putative TSPO agonist, FGIN-1-27, on
      tumor growth in-vivo. RESULTS: In-vitro TSPO knockdown established by stable
      transfection of TSPO antisense gene resulted in HT29 clones displaying
      significantly lower levels of cell death as determined with trypan blue (50%
      less), lower apoptotic rates (28% less), and higher proliferation rates (48% more
      one week after seeding and 27% more two weeks after seeding). Transient
      transfection with anti-human TSPO siRNA resulted in similar viability and
      antiapoptotic effects. In-vivo, the proapoptotic TSPO ligand, FGIN-1-27
      significantly reduced the growth rate of grafted tumors (40% less), in comparison
      with vehicle-treated mice. CONCLUSION: TSPO knockdown by genetic manipulation
      transforms the human HT29 cancer line to a more malignant type in-vitro. In-vivo
      pharmacological treatment with the putative TSPO agonist FGIN-1-27 reduces tumor
      growth of the HT29 cell line. These data suggest that TSPO involvement in
      apoptosis provides a target for anticancer treatment.

PMID- 18806694
TI  - Screening for basic drugs in hair of drug addicts by liquid chromatography/time
      of-flight mass spectrometry.
AB  - Hair analysis in forensic and clinical toxicology has been strongly focused on
      drugs of abuse, and comprehensive, drug class-independent screening methods based
      on mass spectrometric detection have not been applied to date. In this study, a
      qualitative drug screening method by liquid chromatography coupled to time-of
      flight mass spectrometry, earlier developed and evaluated for forensic
      toxicological urine analysis, was adapted for screening of basic drugs in hair.
      The method included alkaline hydrolysis, purification with mixed-mode solid phase
      extraction, and analysis by liquid chromatography coupled to time-of-flight mass
      spectrometry with automated data analysis and reporting. Identification was based
      on accurate mass, isotopic pattern fit, and retention time, if available.
      Analysis of 32 hair samples from deceased drug addicts revealed 35 different
      drugs. The drug classes identified included antidepressants, antipsychotics,
      antiepileptics, amphetamines, opioids, beta-blockers, a benzodiazepine, a
      hypnotic, a local anesthetic, an antiemetic, and an antipyretic analgesic. The
      findings were in good agreement with the findings in blood and urine by other
      methods. Moreover, information about previous drug use not evident in the
      analysis of other matrices was obtained in the majority (72%) of the cases.
      Tramadol was an especially predominant finding, suggesting tramadol abuse as an
      opioid substitute. One apparent false-positive finding was identified. The mean
      and median mass accuracies of positive findings were 2.3 and 1.8 ppm,
      corresponding to 0.5 and 0.4 mDa, respectively. Cutoff values for tramadol and
      methamphetamine in hair were 100 and 200 pg/mg, respectively. The method proved
      to be a simple and straightforward tool for comprehensive screening of basic
      drugs in hair.

PMID- 18806695
TI  - Population pharmacokinetics of atazanavir in human immunodeficiency virus
      infected patients.
AB  - The aim of this study was to determine the population pharmacokinetic (PK)
      parameters of atazanavir in adult human immunodeficiency virus-infected patients
      to build up a Bayesian strategy for dosage regimen individualization. This was an
      observational study of patients treated with the once-daily regimen atazanavir
      associated with 100 mg of ritonavir. Blood samples were drawn at steady state at
      various times ranging from 1 to 26 hours postdose. Atazanavir plasma
      concentrations were determined by a validated reverse-phase high-performance
      liquid chromatography method. PK analysis of the atazanavir population was
      performed using a nonlinear mixed-effects model (NONMEM version 6). One hundred
      eighty-seven patients were included in the study. The atazanavir doses prescribed
      were 300 mg (n = 169), 400 mg (n = 12), 200 mg (n = 1), and 150 mg (n = 5). The
      atazanavir population PK was described using a 1-compartment model with first
      order absorption. Mean PK parameter estimations (95% confidence interval,
      coefficients of variation %) were as follows: oral clearance (CL) = 7.6 L/h (6.9
      8.3; 34%), volume of distribution (V) = 80.8 L (67.4-94; 37%), and absorption
      constant rate (Ka) = 1.05 hours (0.01-2.09; 156%). The mean estimated half-life
      (T-half) was 7.5 hours (95% confidence interval: 7.2 -7.8 hours). The estimated T
      half of atazanavir was in agreement with that previously reported of 8.6 and 8.8
      hours. We observed a wide interpatient variability for the PK parameters,
      especially for Ka. This population approach allowed us to determine atazanavir PK
      parameters in human immunodeficiency virus-infected patients in a real-life
      context and to perform Bayesian analysis to predict Ctrough from samples
      collected at any moment during the dosing interval. This could therefore improve
      therapeutic drug monitoring interpretations and provide an interesting tool for
      correlation with virologic data.

PMID- 18806696
TI  - Clinical significance of a CYP2D6 poor metabolizer--a patient with schizophrenia
      on risperidone treatment.
AB  - A case of a 46-year-old woman with schizophrenia who was treated with risperidone
      and followed up for 1 year is reported. She was genotyped as a CYP2D6 poor
      metabolizer (PM): CYP2D6-4*/*6, which was confirmed by a dextromethorphan (DM)
      test (metabolic ratio = 5.8). Genotypes of ABCB1 (MDR1) were 2677TT and 3435TT.
      Because risperidone is CYP2D6 and P-glycoprotein substrate, the patient might
      have been expected to accumulate risperidone and suffer from significant side
      effects. However, the patient tolerated the drug extremely well. Plasma
      concentration of risperidone was 73.2 nmol/L and of 9-OH-risperidone was below
      the limit of quantitation (6.1 nmol/L). Target range of risperidone plus 9
      hydroxyrisperidone is 50-150 nmol/L. During the follow-up, patient was
      continuously taking 3 mg/day of risperidone. Plasma levels of risperidone and 9
      OH-risperidone were 70.2 and 18.1 nmol/L, respectively. We repeated a DM test,
      metabolic ratio was 3.6, thus confirming that the patient remained a PM.
      Psychopathology was assessed with Positive and Negative Syndrome Scale, and
      stable remission of illness was achieved over the stated period. No adverse
      effects were observed or reported by the patient. We conclude that PM phenotype
      for CYP2D6 does not necessarily have clinical significance in regard to
      risperidone treatment. DM and risperidone are both CYP2D6 and P-glycoprotein
      substrates and significant interactions might occur with both drugs, in parallel
      with the possible impact of ABCB1 and CYP2D6 polymorphic gene variants.

PMID- 18806697
TI  - Pharmacodynamics of mycophenolic acid in CD4+ cells: a single-dose study of IMPDH
      and purine nucleotide responses in healthy individuals.
AB  - Mycophenolate mofetil is used in rejection prophylaxis after allograft
      transplantation. The highly variable pharmacokinetics and pharmacodynamics (PD)
      of the active moiety mycophenolic acid (MPA) render this drug attractive for
      therapeutic monitoring. The aim of this study was to characterize the exposure
      response relationship for MPA to guide future strategies for individualized
      therapy based on PD monitoring. A single-dose (100, 250, 500, and 1000 mg
      mycophenolate mofetil) crossover exposure-response study of MPA PD in CD4 cells
      was performed in 5 healthy individuals. The activity of inosine 5'-monophosphate
      dehydrogenase (IMPDH) at time 0 ranged from 1.2 to 7.2 pmol per 10 cells/min.
      IMPDH was strongly inhibited by MPA; MPA EC50 (concentration required for 50%
      inhibition) of 2.3 mg/L was determined by a pooled data analysis. Decreased IMPDH
      gene expression was associated with the exposure to MPA. There were no immediate
      reductions of guanine nucleotides. On the contrary, a trend toward increased
      guanosine triphosphate was observed. IMPDH activity AUC0-12h approached maximum
      reduction at MPA AUC0-12h 22 mg x h/L (corresponding to the 500 mg dose), whereas
      plasma concentrations exceeding approximately 6 mg/L did not further increase the
      IMPDH inhibition. The results suggest that guanine nucleotides in circulating
      lymphocytes may not serve as immediate response biomarkers to MPA. Strategies for
      preventing over- or underexposure to MPA may be developed by means of IMPDH
      activity combined with MPA concentration measurement.

PMID- 18806698
TI  - Probiotics, prebiotics, and new foods.

PMID- 18806699
TI  - Understanding why probiotic therapies can be effective in treating IBD.
AB  - Probiotics, for the treatment of inflammatory bowel disease, are a group of
      specific nonpathogenic bacteria that are functionally and genetically defined by
      their ability to reduce inflammation in the intestine. Although probiotics also
      seem to have broad beneficial effects in humans, both as a food and as a
      therapeutic agent, there are specific identified mechanisms in some, but not all,
      of these bacteria that are important relative to the pathogenesis of inflammatory
      bowel disease. Recently, studies relative to the mechanism of action of
      probiotics have identified that these organisms can have a direct effect on
      epithelial cell function and intestinal health, including enhancing epithelial
      barrier function, modulating epithelial cytokine secretion into an anti
      inflammatory dominant profile, altering mucus production, changing bacterial
      luminal flora, modifying the innate and systemic immune system, and inducing
      regulatory T-cell effects. For probiotics to have a therapeutic role in the
      management of clinical inflammatory bowel disease, their therapeutic mechanism of
      action must be aligned with the pathogenic mechanism of action of the disease. In
      this regard, the role of probiotics for the clinical treatment of inflammatory
      bowel disease is emerging as the mechanisms and pathogenesis are being unraveled.
      It remains clear that probiotics are able to reduce gastrointestinal inflammation
      by exerting positive effects on epithelial cell and mucosal immune dysfunction.

PMID- 18806700
TI  - Probiotics in critically ill patients.
AB  - Severe sepsis with associated multisystem organ dysfunction is a leading cause of
      death in patients hospitalized in intensive care units. The gastrointestinal
      system plays a key role in the pathogenesis of multisystem organ dysfunction
      owing to a breakdown of intestinal barrier function and increased translocation
      of bacteria and bacterial components into the systemic circulation. During
      critical illness, alterations occur in gut microflora owing to several factors,
      including changes in circulating stress hormones, gut ischemia,
      immunosuppression, the use of antibiotics, and lack of nutrients. The importance
      of endogenous strains of probiotic bacteria such as Bifidobacterium and
      Lactobacillus in maintaining intestinal barrier function and also in modulating
      mucosal and systemic immune responses is becoming evident from numerous studies.
      Bacteria in synbiotic (prebiotic and probiotic combinations) and probiotic
      (mutistrain combinations) preparations are being used experimentally in the
      treatment of acute pancreatitis, liver transplantation, and in trauma patients.
      Recent studies have shown treatment of patients with multiple trauma or acute
      pancreatitis with synbiotic preparations resulted in reduced rates of infection,
      sepsis, and mortality in patients. Enterally fed patients in the intensive care
      unit treated with a probiotic compound demonstrated enhanced immune function and
      decreased incidence of diarrhea. Results from these clinical trials are
      encouraging, and warrant further investigation to clarify which probiotic
      bacterial strains are of most benefit to this population.

PMID- 18806701
TI  - Balsalazide plus high-potency probiotic preparation (VSL[sharp]3) in the
      treatment of acute mild-to-moderate ulcerative colitis and uncomplicated
      diverticulitis of the colon.
AB  - Balsalazide is a 5-amino salicylic acid prodrug well-tolerated and effective in
      treating acute ulcerative colitis. VSL[sharp]3, a high-potency probiotic mixture,
      has proved to be effective in preventing flare-ups of chronic pouchitis and in
      obtaining remission of mild-to-moderate ulcerative colitis. Recent studies found
      the association of low-dose balsalazide/VLS no. 3 effective in treating mild-to
      moderate ulcerative colitis and in preventing the recurrence of uncomplicated
      diverticulitis of the colon. In this paper, the framework for using this
      association to treat ulcerative colitis or to prevent the recurrence of colonic
      diverticulitis is reviewed, and 2 studies on this therapeutic approach are
      briefly summarized.

PMID- 18806702
TI  - Probiotics and irritable bowel syndrome: rationale, mechanisms, and efficacy.
AB  - To review the rationale and current evidence for the efficacy of probiotics in
      the treatment of irritable bowel syndrome (IBS), the following specific questions
      are addressed from a review of the published literature: Are bacterial flora
      altered in IBS? Is infection a significant risk factor for IBS? How prominent is
      the inflammation in IBS? Do probiotics change bacterial flora? Do probiotics
      adhere to mucosa? What are the potential mechanisms of action of probiotics in
      IBS: immune function, motor, secretory, sensory, and fermentation? What is the
      efficacy of probiotics in IBS?

PMID- 18806703
TI  - Use of VSL[sharp]3 in the treatment of rotavirus diarrhea in children:
      preliminary results.
AB  - We conducted a double-blind randomized placebo-controlled study to evaluate
      efficacy and tolerability of VSL[sharp]3 (CD Pharma India) in the treatment of
      acute rotavirus diarrhea in children. The patients were randomly assigned to
      receive 4 days of oral treatment with VSL[sharp]3 probiotic mixture or placebo in
      addition to usual care for diarrhea. RESULTS: Out of 230 rotavirus-positive acute
      diarrhea children, 224 children completed the study, (113 in the drug group and
      111 in the placebo group). At recruitment on Day 1, there were no significant
      differences between the 2 groups in terms of frequency of vomiting, mean loose
      stool frequency, stool consistency, and mean frequency of oral rehydration salts
      (ORS) and intravenous fluids administered. On Day 2, a lower mean stool frequency
      and improved stool consistency was noted in the drug group, which achieved
      statistical significance. This was also reflected in the lower volume of ORS
      administration in the drug group. Even on Day 3, mean loose stool frequency and
      frequency of ORS use and frequency of intravenous fluid use was significantly
      lower in the drug group. The differences in the frequency of loose stools
      persisted till 8 hours of Day 4. After this, as the placebo group also showed
      spontaneous improvement the difference between the 2 groups in terms of the
      overall stools frequency became comparable. However, the overall ORS requirement
      continued to be significantly lower in the drug group even on Day 4. The overall
      recovery rates were significantly better in the drug group compared with placebo.
      No side effects were noted with the use of the probiotic mixture. Use of
      probiotic mixture VSL[sharp]3 in acute rotavirus diarrhea resulted in earlier
      recovery and reduced frequency of ORS administration reflecting decreased stool
      volume losses during diarrhea.

PMID- 18806704
TI  - Use of probiotic bacteria for prevention and therapy of allergic diseases:
      studies in mouse model of allergic sensitization.
AB  - Probiotic bacteria as modulators of the immune response have been intensively
      studied in reducing the risk of immune-mediated diseases, including atopic
      diseases. Results from in vitro studies demonstrated that probiotics may modify
      the polarization of immune cells, supporting potential therapeutic effects in
      atopic diseases. Several clinical studies have been designed to explore the
      effective role of probiotics in the modulation of allergic diseases. The results
      of these studies, although promising, are not conclusive yet and are considered
      insufficient to recommend probiotics as a part of standard therapy in any
      allergic conditions. In vivo studies on animal models can provide useful
      information on the immunologic mechanisms responsible for the potential
      antiallergic effects of probiotic bacteria. The immunomodulatory activity of the
      probiotic mixture VSL#3 has been studied in the mouse models of allergic
      sensitization and anaphylaxis developed in our laboratory with inhalant and food
      allergens, according to a prophylactic setting by the intranasal route (inhalant
      allergy model) or a therapeutic setting by the oral route (food allergy model).
      Intranasally delivered probiotic bacteria prevented the development of Parietaria
      major allergen-specific response, by down-regulating T helper cell 2 responses at
      the local and systemic level. Oral therapeutic treatment was able to reduce both
      systemic and local anaphylactic symptoms induced by oral challenge with the
      sensitizing allergen Shrimp Tropomyosin. The induction of protective immune
      responses at the sites of allergen exposure linked to counterregulatory local and
      systemic immune responses by mucosal delivery of probiotic bacteria mixtures
      might become an effective strategy in the prevention and therapy of allergic
      diseases.

PMID- 18806705
TI  - Solute carriers (SLC) in inflammatory bowel disease: a potential target of
      probiotics?
AB  - Transporter proteins of the solute carriers (SLCs) family play a role in
      epithelial permeability and barrier function in the intestine, and polymorphisms
      in SLC genes are associated with inflammatory bowel disease. Many SLCs also
      mediate the bioavailability of pharmaceutical compounds, and the modulation of
      such transport systems to increase drug efficacy is, therefore, of great
      interest. We have undertaken a large-scale project to evaluate whether bacteria
      can modulate the expression of SLCs in the intestine. Here we report the effect
      of VSL[sharp]3 (a high-potency probiotic preparation) on the expression of 3
      large solute carrier families, SLC4, SLC21, and SLC22, which are involved in the
      transport of bicarbonates, organic anions and cations, and affect the
      bioavailability of several pharmaceutical compounds. Two groups of animals
      (VSL[sharp]3 and phosphate-buffered saline controls) were studied for SLC
      expression in the intestine by Real-Time PCR at the beginning (day 1) and at the
      end (day 20) of the treatment, and 7 days after the interruption of the
      treatment. An effect of VSL[sharp]3 administration was detected on the expression
      of 10% of the studied genes. This reached statistical significance (P=0.01) for
      the poorly characterized sodium-borate cotransporter SLC4A11, which showed a 5
      times lower expression in VSL[sharp]3 than in control mice on day 1 of probiotic
      treatment. VSL[sharp]3-driven changes in the expression levels of SLC
      transporters might contribute to its reported effects on intestinal permeability.
      The elucidation of SLC4A11 function in the intestine will be the key to fully
      evaluate the relevance of specific findings.

PMID- 18806706
TI  - Indications and challenges of probiotics, prebiotics, and synbiotics in the
      management of arthralgias and spondyloarthropathies in inflammatory bowel
      disease.
AB  - Arthralgia and spondyloarthropathy of the peripheral and the axial joints are
      common in patients with inflammatory bowel diseases. Evidence for this
      association has been provided by clinical, epidemiologic, and immunologic studies
      confirming the presence of shared inflammatory pathways in gut and joint.
      Bacterial gut infections such as Salmonella typhimurium, Yersinia enterocolitica,
      Shigella, Campylobacter jejuni may induce reactive peripheral arthritis and 20%
      of these patients may develop chronic spondyloarthropathy. It is not certain that
      arthralgias in inflammatory bowel diseases are more frequent than in the general
      population but clinical articular manifestations compatible with
      spondyloarthropathy are present in 10% to 40% of patients with inflammatory bowel
      diseases. These enteropathic peripheral arthropathies without axial involvement
      are subdivided into a pauciarticular of large joints and a bilateral symmetrical
      polyarthropathy. The rationale and the challenges of using prebiotics,
      probiotics, and synbiotics in the management of patients with inflammatory bowel
      diseases with arthralgias and spondyloarthropathy are briefly reviewed. The
      rationale is based on the modulation of the ubiquitous intestinal flora by
      bacteria and their products that have been proven to be safe. The challenge is to
      find the "window of opportunity" to treat the evolutionary stage of joint
      inflammation. It seems to us that the major aim is not to treat patients who have
      a self-limited inflammatory joint disorder, but those patients with persistent
      arthralgias in an early phase of the disease. Seronegative and seropositive
      patients with early arthritis, before damage may occur, could be managed by this
      approach to improve the quality of life and to positively influence the natural
      course of the disease.

PMID- 18806707
TI  - Microbial biofilm communities in the gastrointestinal tract.
AB  - The human gastrointestinal tract is colonized throughout its length by complex
      luminal and mucosal microbiotas. Owing to sampling restrictions, most of the
      studies done to date have concentrated on luminal material. Recently, however,
      there has been an upsurge in interest in the role of microbial communities that
      occur in biofilms on surfaces in the gut. In the human biota, biofilms have been
      shown to exist on artificial surfaces and devices implanted in the host, on
      particulate materials in the gut lumen, and on the colonic mucosa. Owing to their
      proximity to host tissues, mucosal bacteria interact more readily with the gut
      epithelium and immune system than their luminal counterparts, and recent research
      indicates that they play an important role in health and disease processes.
      Because bacteria growing in biofilms are more resistant to antibiotics than their
      luminal counterparts, there is increased interest in the use of alternative
      therapeutic strategies to target potential pathogens on the mucosal surface,
      especially with respect to applications involving probiotics, prebiotics, and
      synbiotics.

PMID- 18806708
TI  - Innate immunity in Crohn's disease: the reverse side of the medal.
AB  - The etiology of Crohn's disease (CD) remains poorly understood. Both mice and
      human studies suspected a perverse link between the microbiota and the lining of
      the gut mucosa. There is now emerging evidence that suggests that such a
      pathologic condition might result from an overly aggressive immune response to
      microbial antigens in genetically predisposed individuals. However, the multiple
      pathophysiologic processing steps linking environmental exposure to the clinical
      expression of CD are, for the most part, unknown. Herein, we review evidences
      reflecting a general causing defect of the innate immune function of the
      intestinal mucosa of CD patients, which might lead to a sustained microbial
      induced inflammatory response. Changing the paradigms of CD pathophysiology might
      lead to entirely new therapeutic approaches aiming to boost the innate immune
      response.

PMID- 18806709
TI  - Probiotics and severe acute pancreatitis.
AB  - Acute pancreatitis (AP) is an acute inflammatory process ranging from mild forms
      to severe disease with high rates of mortality. In this disease, enteral
      nutrition helps in maintaining the integrity of the gut barrier, with consequent
      decreased bacterial translocation, a key factor in limiting the complications in
      severe AP. Modulation of the intestinal flora through the administration of
      probiotics (PBs) has thus an intriguing rationale as possible treatment option.
      Their role in this setting has been investigated both in animal models and
      clinical trials in the last few years; however, their use has never been
      recommended or even cited by existing guidelines. We analyzed the literature in
      search of the existing data from human and animal models studies evaluating the
      effect of PB administration in AP to highlight existing evidence. An interesting
      scenario emerges from the the papers that have been evaluated. The adjunct of PBs
      in the treatment of AP may show some advantage in terms of the reduction of
      infectious complications. Nevertheless, more data on efficacy and safety from a
      larger and stringently designed study are eagerly waited.

PMID- 18806711
TI  - The cardiometabolic syndrome in the adolescent.
AB  - With recent increases in obesity among the pediatric age group, problems
      previously seen primarily in adults, such as type 2 diabetes and essential
      hypertension, are being more frequently diagnosed in young individuals. This has
      lead to interest in the development of the constellation of cardiovascular risk
      factors known as the cardiometabolic syndrome in the pediatric population. With
      these cardiovascular risk factors manifesting earlier, there is reason to be
      concerned that the earlier and longer exposure will result in earlier
      presentation of cardiovascular and microvascular events and lead to a devastating
      public health impact. In this review we examine the evidence for the increased
      prevalence of the cardiometabolic syndrome in the pediatric age group and the
      impact of childhood overweight on the prevalence of this syndrome in children as
      well as the impact on adult obesity and metabolic derangements.

PMID- 18806710
TI  - Lessons learned from studies of the natural history of diabetic nephropathy in
      young type 1 diabetic patients.
AB  - Diabetic Nephropathy (DN) remains the leading cause of end stage renal disease
      (ESRD) in the Western world, responsible for nearly half of all new ESRD cases in
      the USA (1). DN develops in 20-25% of patients with type 1 diabetes (T1DM) (2)
      and, although risk of DN is clearly related to glycemic control (3,4), other
      variables including genetic propensity (5) are needed to explain why only a
      minority T1 DN patients progress to ESRD. The clinical manifestations of DN
      including increasing levels of urinary albumin excretion (AER), rising blood
      pressure (BP) and falling glomerular filtration rates (GFR) are closely related
      to renal structural abnormalities of DN (5,6). These glomerular, tubular,
      vascular and interstitial lesions are strongly correlated with these functional
      abnormalities especially when non-linear analysis models are used (6,7). This is
      because DN's natural history is one of clinical silence for years to decades
      during which time serious underlying renal lesions may be developing. Once the
      clinical manifestations, including the development of persistent microalbuminuria
      [(MA); (AER 20-200 microg/min)] are present, the structural injury is often far
      advanced (8). Moreover the nature of the renal lesions changes following the
      development of overt proteinuria so that the further decline in GFR is now
      associated with focal and global glomerular sclerosis and tubulo-interstitial
      injury which probably accelerates the GFR decline towards ESRD (7). Since
      interventions at these late stages of disease may only slow but not completely
      arrest the inexorable progression towards renal failure (9), understanding early
      natural history becomes important. Since DN structurally and functionally is a
      progressive disease; it is reasonable to presume that patients that either do not
      develop the earlier lesions of DN or develop them very slowly will not progress
      within their lifetime to stages of advanced renal structural injury and ESRD. We
      therefore considered it important to understand the early natural history of
      diabetic nephropathy and formed the International Diabetic Nephropathy Study
      Group (IDNSG) in order to investigate the early stages of DN in young T1DM
      volunteers. The design of the Natural History Study (NHS) (9) has been reported.
      The IDNSG participating institutions included 3 university centers (McGill
      University, Montreal, Canada with affiliations with the University of Sherbrooke,
      Sherbrooke, Canada, the Ottawa Civic Hospital, and the Childrens Hospital of
      Eastern Ontario; the Department of Pediatrics, University of Minnesota Medical
      School with affiliations at St Paul Children's Hospital and the International
      Diabetes Center in Minneapolis; the Robert Debre Hopital in Paris with
      affiliations with Hopital Saint Louis). The data coordinating center for the NHS
      was in the Department of Epidemiology and Biostatistics at McGill University and
      light microscopy readings were carried out at INSERM Unite 192 at the Hopital
      Necker-Enfants Malades in Paris. Patients could be included if they had type 1
      diabetes for 2-20 years, had onset of diabetes before age 31, had AER less than
      100 mug/min and GFR > or = 90 ml/min/ 1.73m2 (9). Patients also had to be
      normotensive for their age and sex and have no other significant renal or
      systemic disease. Quarterly studies included measurements of blood pressure,
      (BP), urinary albumin excretion rate (AER), hemoglobin A1C (HbA1C), GFR, and
      renal plasma flow (RPF). Renal biopsies were performed at baseline and after 5
      years in the study. The primary goal of the study was to determine the clinical
      predictors of the baseline biopsy and baseline clinical and renal structural
      predictors of the changes between the baseline and the 5 year biopsy. The
      longitudinal structural studies are still in analysis and this paper will mainly
      review the cross sectional studies that have been completed to date.

PMID- 18806712
TI  - Continuous monitoring of blood pressure in children and adolescents,a review of
      the literature.
AB  - Continuous or ambulatory blood pressure monitoring (CBPM or ABPM) is becoming a
      useful tool in the early detection of hypertension in children and adolescents.
      With increased obesity in pediatrics, chronic diseases such as hypertension,
      diabetes, dyslipidemia and metabolic syndrome which was more commonly seen in
      adults in the early years, can now be seen in this population. This review
      provides the clinical reports of the use of CBPM for diagnosis and management of
      hypertension in the pediatric population.

PMID- 18806713
TI  - Albuminuria and diabetic nephropathy.
AB  - Albuminuria is characterized clinically as an early predictor for progression of
      diabetic nephropathy (DN). Proteinuria (macroalbuminuria) is the universal
      finding in progressive renal disease, and is viewed as a measure of the severity
      and determinant for diabetic renal disease progression. Albuminuria is a marker
      for early DN, an independent predictor for mortality, and is associated with
      renal and cardiovascular risks. The definition of albuminuria, its pathogenetic
      role resulting in progressive renal injury, and review of the current literature
      of albuminuria with its relationship to DN are discussed. Albuminuria is a
      predictor of albuminuria progression in DN. Tight glycemic control reduces the
      risk of progression from normoalbumuria to microalbuminuria, as well as from
      microalbuminuria to proteinuria. The relationships between albuminuria and blood
      pressure in renal progression and renal outcomes are examined. Clinical
      strategies and pharmacological agents used in reducing proteinuria in an effort
      to slow the progression of DN are summarized.

PMID- 18806714
TI  - Prevention of type 2 DM: implications for adolescents and young adults.
AB  - Type 2 Diabetes has reached epidemic proportions among adults in the USA and
      worldwide. With the rising epidemic of obesity among children and adolescents, a
      parallel epidemic of type 2 diabetes is also observed in this patient population.
      Control of diabetes and its complications, mainly cardiovascular disease has been
      sub-optimal at best. Therefore, effort trials have been conducted and others are
      ongoing to assess various modalities for diabetes prevention among adults,
      ranging from diet and exercise to pharmacological agents of various classes.
      Recently, concerted efforts have been made for prevention of type 2 diabetes
      among children and adolescents. In this paper we discuss the diabetes prevention
      rationale and methods among adults and the implications of these efforts for
      children and adolescents. We also highlight the ongoing efforts for diabetes
      prevention in trials specifically designed to address the adolescent population.

PMID- 18806715
TI  - Mauriac syndrome: growth failure and type 1 diabetes mellitus.
AB  - Growth failure in Type 1 Diabetes Mellitus (T1DM) can occur for several reasons.
      Mauriac syndrome is a rare cause of severe growth failure in T1DM. There may be
      different forms and etiologies involved in Mauriac syndrome. However, there are
      common features noted in these patients. We have compiled a review of cases
      reported in English in the last 30 years. With adequate insulin treatment there
      is reversal of growth failure and hepatomegaly if present. However, overly
      aggressive insulin delivery could result in rapid deterioration of diabetic
      retinopathy and nephropathy. Close monitoring of growth and pubertal maturation
      in children with T1DM is essential.

PMID- 18806716
TI  - Celiac disease in African American children with type 1 diabetes mellitus in
      inner city Brooklyn.
AB  - OBJECTIVE: There is a strong evidence for association between type 1 diabetes and
      Celiac Disease. Up to 8% of patients with type1 diabetes have characteristic
      features of CD on small intestinal biopsy. Type 1 diabetics who have HLA DQ2 or
      DQ8 are at risk for CD. However most of this data is from studies conducted in
      Europe, with mostly Caucasian population. This study aims to identify the
      prevalence of celiac disease in African American children with Type1 diabetes in
      inner city Brooklyn, New York. METHODS: IgA and IgG Antigliadin antibodies, IgA
      tissue transglutaminase and HLA typing was measured in blood collected from 34
      children with type1 diabetes mellitus. Patients with positive anti tissue
      transglutaminase antibody underwent small intestinal biopsy. RESULTS: 17 patients
      had elevated IgG AGA, none showed elevated IgA AGA. Only one patient had elevated
      IgA and anti tTG levels, and a normal small intestinal biopsy. 28 patients had
      HLA DQ2 or DQ8 present. CONCLUSIONS: 94% of the African American children with
      type1 diabetes were serology negative for celiac disease inspite of having the
      predisposing HLA haplotype. Only one patient was positive for anti tTG antibody,
      with a negative small intestinal biopsy, the prevalence of celiac disease in this
      population may not be similar to the other populations. Pediatric Endocrinology
      in review 990,2008.

PMID- 18806717
TI  - Early detection and treatment of diabetic nephropathy.
AB  - Renal involvement in diabetes, known as diabetic nephropathy (DN), is a
      progressive disease and occurs as a result of direct and indirect effects of
      hyperglycemia. DN is a serious public health concern because it is the leading
      cause of end stage renal disease (ESRD) in most developed countries and is
      associated with increased cardiovascular mortality and morbidity. DN is
      characterized by an initial period of glomerular hyperfiltration, associated with
      progressively increasing proteinuria, followed by a gradual decline in glomerular
      filtration rate, resulting in ESRD. Prevention of DN depends on awareness of risk
      factors for DN, screening for microalbuminuria and hypertension, monitoring
      glycemic control, and initiating or modifying treatment as needed. Risk factors
      for development of DN include hyperglycemia, hypertension, positive family
      history of nephropathy and hypertension, and smoking. Significant advances have
      been made in recent years in understanding the pathogenesis of DN, raising the
      possibility that newer therapies may prevent or slow the progression of DN.

PMID- 18806718
TI  - Can a change in policy of complementary infant feeding reduce the risk for type 1
      diabetes and celiac disease?
AB  - According to recent epidemiologic evidence, introducing solids while infants are
      still breastfed, and in any case not before the fourth month of life, could have
      positive impact on immune-related chronic disorders such as Type 1 Diabetes and
      coeliac disease.

PMID- 18806719
TI  - Growth hormone responsiveness: peak stimulated growth hormone levels and other
      variables in idiopathic short stature (ISS): data from the National Cooperative
      Growth Study.
AB  - HYPOTHESIS: In children with idiopathic short stature (ISS), growth hormone (GH)
      response to a provocative test will be inversely related to the first year
      response to hGH and be a variable accounting for a degree of responsiveness.
      BACKGROUND: Because high levels of GH are a characteristic of GH insensitivity,
      such as in Laron syndrome, it is possible that a high stimulated GH is associated
      with a lower first year height velocity among children diagnosed as having ISS.
      METHODS: We examined the relationship between the peak stimulated GH levels in 3
      ISS groups; GH >10 -<25, 25-40, and >40 ng/mL and the first year growth response
      to rhGH therapy. We also looked at 8 other predictor variables (age, sex, height
      SDS, height age, body mass index (BMI), bone age, dose, and SDS deficit from
      target parental height. Multiple regression analysis with the first year height
      as the dependent variable and peak stimulated GH was the primary endpoint. The
      predictive value of adding each of the other variables was then assessed.
      RESULTS: Mean change in height velocity was similar among the three groups, with
      a maximum difference among the groups of 0.6 cm/yr. There was a small but
      statistically significant correlation (r=-0.12) between the stimulated GH and
      first year height velocity. CONCLUSIONS: The small correlation between first year
      growth response and peak GH is not clinically relevant in defining GH resistance.
      No cut off level by peak GH could be determined to enhance the usefulness of this
      measure to predict response. Baseline age was the only clinically significant
      predictor, R-squared, 6.4%. All other variables contributed less than an
      additional 2% to the R-squared.

PMID- 18806720
TI  - Evaluation of postnatal growth in very low birth weight infants: a
      neonatologist's dilemma.
AB  - Very low birth weight (VLBW) infants' survival has greatly increased in the last
      few decades thanks to the improvement in obstetrical and neonatal care. The
      correct evaluation of postnatal growth of these babies is nowadays of primary
      concern, although the definitions of their optimal nutrition and postnatal growth
      pattern are still controversial. It is known that VLBW infants have a specific
      postnatal growth pattern markedly different from that of higher birthweight full
      term infants. Prospective longitudinal studies are needed to trace VLBW infants
      growth charts for weight, length and head circumference. These charts will be a
      useful tool to monitor postnatal growth of VLBW infants both during
      hospitalisation and after discharge, up to 2 or 3 years of age. A useful tool in
      VLBW infants growth evaluation could also be absolute velocity charts that,
      allowing a better and earlier identification of growth anomalies, could permit
      the observation of phenomena not yet visible on distance charts. Very low birth
      weight (VLBW) infants' survival has greatly increased in the last few decades
      thanks to the improvement in obstetrical and neonatal care. These neonates
      represent about 1-1.5% of all live born infants in developed countries (1) and
      they constitute the large majority of the population in neonatal intensive care
      units (NICUs). For this reason, the correct evaluation of their postnatal growth
      is of primary concern nowadays although the definitions of optimal nutrition and
      postnatal growth pattern are still controversial.

PMID- 18806721
TI  - Thyroid nodules and cancers in children.
AB  - The incidence of thyroid nodules in children is estimated to be 1 to 1.5% based
      on clinical examination. Children with thyroid nodules, compared to adults with
      thyroid nodules, have a fourfold greater risk of developing malignant thyroid
      disease. Differentiated thyroid carcinoma is the most common pediatric endocrine
      tumor, constituting 0.5-3% of all childhood malignancies. The thyroid is one of
      the most frequent sites of secondary neoplasm in children who receive radiation
      therapy for other malignancies. Thyroid carcinoma has been studied extensively in
      adults. However, the pediatric literature on this subject is much less complete,
      owing to the rarity of its diagnosis. This article reviews the predisposing
      factors, genetics, pathology, pathogenesis , clinical presentation, detailed
      treatment and follow-up management of children with thyroid carcinoma.
      Additionally, a discussion regarding the controversial aspects of radioiodine
      therapy in children is included.

PMID- 18806722
TI  - The inflammatory process of adipose tissue.
AB  - Obesity and inflammation are highly integrated processes in the pathogenesis of
      insulin resistance, diabetes, atherosclerosis, and non-alcoholic fatty liver
      disease. The evidence that obesity can be regarded as an inflammatory disease
      comes from numerous studies showing a moderate increase of circulating
      inflammatory factors in obese patients and the identification of different types
      of immune cells infiltrating the human adipose tissue. Obesity may induce a pro
      inflammatory state, which can cause or worsen insulin resistance in adipose
      tissue, skeletal muscle, and liver. The causative factors of this inflammation
      process in obesity are not entirely understood, but adipose tissue seems to play
      an important role in the relationship between obesity and chronic inflammation.
      Increased infiltration of adipose tissue with immune cells could cause adipose
      tissue insulin resistance via autocrine and paracrine cytokine/adipokine
      signalling, which contributes to systemically decreased insulin sensitivity via
      endocrine signalling. On the other hand, obesity-induced inflammation could
      represent a compensatory mechanism for increased adipose tissue turnover in obese
      states, which might protect obese individuals against deleterious effects of fat
      accumulation. A better understanding of the mechanisms and molecular components
      of obesity induced inflammatory response might lead to identifying novel
      therapeutic targets to prevent obesity-related complications.

PMID- 18806723
TI  - Estrogens and growth.
AB  - Estrogen plays a key role in the regulation of growth in both genders, via its
      stimulation of the pubertal growth spurt and mediation of epiphyseal fusion.
      Mouse knockout models suggest a differential effect of oestrogen receptor (ER)
      alpha and beta on the growth plate, with ER beta possibly being more important in
      regulating epiphyseal fusion. Epiphyseal fusion may also depend on growth plate
      senescence, which is regulated by oestrogen. While molecular mechanisms for
      oestrogen's actions remain unclear, local production of oestrogen may be
      important for growth. Aromatase inhibitors appear to be effective in improving
      final height outcome in short stature, however long term safety data is lacking
      particularly in regards to reproductive function. Future studies are required to
      further understand the mechanisms by which ER alpha and ER beta affect growth
      plate function, while longer term studies of aromatase inhibitor usage,
      preferably utilising animal models, are required to verify the safety of these
      compounds.

PMID- 18806724
TI  - Lawson Wilkins Pediatric Endocrine Society, Honolulu HI, MAY 2-5, 2008.

PMID- 18806725
TI  - Treatment approaches for growth failure.

PMID- 18806726
TI  - Treatment approaches for growth failure.

PMID- 18806727
TI  - Pharmacokinetic principles of immunosuppressive drugs.
AB  - The combination of synergistic drugs is the main strategy to prevent early acute
      rejection and to provide long-term effective rejection prophylaxis. Evaluation of
      drug concentrations to guide drug dosing is routinely established for calcineurin
      inhibitors CNIs and mTOR inhibitors. Arguments in favour of therapeutic drug
      monitoring TDM are the large inter-patient variability of many immunosuppressants
      with their potential for severe toxicity and drug-to-drug interactions. The
      manuscript discusses several confounding factors, which influence the appropriate
      therapeutic window. These include decreasing risk of rejection over time,
      cumulative risk for toxicity with time, and the synergistic potential of
      combination immunosuppressive therapy with respect to efficacy and shared
      toxicities. In addition, a long list of donor and recipient characteristics have
      a direct or indirect effect on the therapeutic window, but have not been
      evaluated in rigorous, prospective trials. Unfortunately, only a very small
      number of adequately powered, prospective randomized trials evaluate different
      therapeutic windows for immunosuppressants or even the utility of TDM at all.
      Other problems of TDM include the inherent variability of absorption and drug
      levels and a suboptimal correlation between pharmacokinetic surrogate parameters
      and drug exposure for most drugs. Drugs with a high intra-patient day-to-day
      variability may be less suited for TDM compared to drugs with a high inter
      patient, but low intra-patient variability. Furthermore it is not known whether
      the same parameter is suitable for controlling efficacy as well toxicity. With
      cumulative overexposure the effect of time might be more far more important than
      a specific level at a given time point and provides another fundamental
      dimension. A new approach of TDM, classified as pharmacodynamic (PD) drug
      monitoring, which directly reflects the drug's biological effects has been
      proposed to better assess the individual state of immunosuppression, however
      difficult test systems and lack of prospective trials limit this approach
      currently. Future studies have to take these considerations into account in order
      to better guide immunosuppression towards a more individualized therapy, which
      remains an important goal in transplant medicine.

PMID- 18806728
TI  - Influence of interactions between immunosuppressive drugs on therapeutic drug
      monitoring.
AB  - With the emergence of more immunosuppressive drug combinations in
      transplantation, the number and complexity of drug interactions have increased
      and constitute a growing challenge for clinicians. Especially, clinically
      relevant immunosuppressive drug interactions require prompt identification,
      intensified monitoring of drug concentrations and adequate dosing responses. The
      drug interaction whereby cyclosporine, as opposed to tacrolimus, inhibits the
      enterohepatic (re)circulation of mycophenolic acid and its inactive MPAG
      metabolite, will result in significantly lower dose-corrected MPA concentrations
      in cyclosporine-treated patients which in turn will lead to early clinical MPA
      underexposure in 50% of patients receiving 2 grams of MMF per day. Also, when
      reducing or withdrawing cyclosporine or switching to tacrolimus as alternative
      calcineurin-inhibitor and vice versa, this important drug interactions needs to
      be taken into consideration. The combination of cyclosporine and the
      proliferation signal inhibitors (PSI) sirolimus and everolimus, requires dose
      reductions of both drugs because of a well-established synergistic drug
      interaction which will lead to increased nephrotoxicity when left unadjusted.
      Despite the observations that clinically important drug interactions between PSI
      and tacrolimus are apparently lacking, switching between calcineurin-inhibitors
      in renal recipients requires intensified monitoring of PSI concentrations.
      Finally, when corticosteroid doses are substantially reduced or completely
      withdrawn from a tacrolimus-based immunosuppressive regimen, a moderate increase
      of tacrolimus concentrations will ensue, albeit without any clearly described
      clinical consequences. More attention for clinically relevant immunosuppressive
      drug interactions is warranted in this era of tailor-made transplantation
      medicine whereby an increasing number of immunosuppressive drug combinations are,
      not uniquely, but rather sequentially used during the life course of a
      transplanted organ.

PMID- 18806729
TI  - Successful open pulmonary embolectomy for acute massive pulmonary embolism in a
      recent kidney transplant recipient.
AB  - BACKGROUND: Patients with acute massive pulmonary embolus have a high mortality
      even with treatment. For patients in whom thrombolytic intervention is
      contraindicated, surgical pulmonary embolectomy is a viable option. CASE REPORT:
      We present a patient who, four months after kidney transplantation, developed
      acute massive PE with cardiac arrest. He underwent surgical pulmonary embolectomy
      and was discharged two weeks later, with preservation of renal allograft function
      and long-term survival. CONCLUSIONS: While the mortality risk of surgical
      embolectomy is high, survival has been greatly improved by the use of
      cardiopulmonary bypass. Early diagnosis and initiation of aggressive treatment is
      vital to achieving successful outcomes in patients who would otherwise be
      unsalvageable.

PMID- 18806730
TI  - Laparoscopic live-donor nephrectomy with retroperitoneoscopic access - first case
      experience.
AB  - BACKGROUND: Despite observed huge progress in understanding the immunological
      basis of transplantation and the development of new immunosuppressive agents that
      have significantly improved both -- the patient and graft survival, still the
      kidney donation from live volunteers remains the most consistent factor which
      affects the long-term survival. The conventional, open method of donor
      nephrectomy is associated with significant surgical trauma. The laparoscopic live
      donor nephrectomy (LDN) is the alternative for open approach. CASE REPORT: We
      present our experience of the case of laparoscopic removal of the kidney from a
      living donor. We applied retroperitoneoscopic access, the operation time was 210
      minutes. Kidney was implanted shortly after LDN and its immediate function was
      observed. We have observed no serious postoperative complications either in donor
      or recipient. CONCLUSIONS: We hope that this successful initial case of LDN will
      have a positive effect on cooperation between transplantologists and urologists,
      and on rate of kidney donation in Poland.

PMID- 18806731
TI  - Outcome of heart transplantations done in our centre.
AB  - BACKGROUND: We have found no study conducted economic issues on patient outcomes
      after heart transplantation (HTx) in China for further development.
      MATERIAL/METHODS: From May 2004 to February 2006, there were 10 transplants
      performed in 9 male patients in our center: 1 heart lung recipient and 8 heart
      recipient. Among them, 7 lacked health insurance and 2 had insurance. RESULTS:
      Their ages were between 24 years and 43 years (mean 39 years). The number of
      hospitalizations, number of days in hospital per admission, number of emergency
      room visits and mean left ventricular ejection fraction (LVEF) in the year before
      operation were 5.5, 54, 8.1 and 0.19 respectively. After operation, these figures
      decreased significantly to 1.7 (P<0.05), 18 (P<0.05), 1.1 (P<0.05) and 0.70
      (P<0.05) respectively. During the follow up of 370~930d, one of the 9 patients
      who lacked health insurance died of acute rejection due to stopping mycophenolate
      mofetil (MMF) 7 months after operation and the heart lung recipient who also
      lacked health insurance died of pulmonary infection 1 year later. All patients
      who lacked health insurance experience emotional distress. CONCLUSIONS: HTx is a
      good treatment for selected patients with end-stage heart failure (ESHF) and
      future research is to be expected in the fields of insurance coverage to improve
      the quality of life and the Chinese transplant group should be commended for
      their courageous work in the treatment of end stage heart disease under
      challenging circumstances.

PMID- 18806732
TI  - Per-operative changes and related factors during simultaneous pancreas-kidney
      transplantation: first experience at a Brazilian university hospital.
AB  - BACKGROUND: Several factors influence ischemic/reperfusion injury in simultaneous
      pancreas-kidney transplantation (SPKT). Per-operative period is full of intense
      changes in systemic parameters related to pancreatic reperfusion (PR). This work
      aims to study these changes evaluating fluid reposition, need of vasopressors and
      other related factors. MATERIAL/METHODS: Sixteen SPKT enduring patients mean age
      32.4+/-4.76 had metabolic, electrolyte and hemodynamic data evaluated and
      compared at three times. Arterial blood gases, glucose, hematocrit; Na, K; MAP,
      HR and PAP were monitored after skin incision (T1), before and after PR (T2-T3).
      Fluid reposition, vasopressors, endocrine graft recovery and other related
      factors as donors, grafts, surgery team and receptors were also considered.
      RESULTS: Glucose, PaO2, PaCO2 and electrolytes didn't vary along the times. From
      T1v.T2 there was significant metabolic acidosis; T2v.T3 identified tachycardia
      and pulmonary hypertension; T1v.T3 confirmed metabolic acidosis, hemodilution and
      arterial hypotension. Use of crystalloids (8500+/-2909.75 mL), colloids (647.05+/
      492.59 mL), human albumin (8.57+/-2.44 U), fresh frozen plasma (1.06+/-1.91 U),
      platelets (1.86+/-4.16 U) and red packed cells (5.75+/-3.25 U), needs of
      noradrenalin and dobutamin: 37,5% and 6,25%. Endocrine graft recovery median was
      4.15 h. Related factors to donor's: 25.43+/-8.14 years, BMI 23.24+/-1.66, serum
      creatinine 1.1+/-0.47mg/dl, hemodynamically stable and trauma as cause of 50%
      donors brain death; graft storage: cold ischemia time (CIT) median of 12.5 h;
      surgery team: warm ischemia time (WIT) median of 60min; receptors: ASA4, type 1
      diabetes mellitus and end stage renal disease medias of 18.87+/-5.64 and 2+/-1.3
      years. CONCLUSIONS: Our experience confirmed the intense instability related in
      literature caused by PR in SPKT.

PMID- 18806733
TI  - Mayo risk score for primary biliary cirrhosis: a useful tool for the prediction
      of course after liver transplantation?
AB  - BACKGROUND: Survival after orthotopic liver transplantation (OLT) for primary
      biliary cirrhosis (PBC) is excellent. In order to define the optimal time point
      for OLT, the Mayo risk score (MRS) was developed and a score of 7.8 was
      identified for transplantation. However, in reality most recipients are in a bad
      condition with a MRS above 7.8. So far it is still unknown if a higher score is
      associated with more complications after OLT perioperatively and in a long-term
      follow-up. Therefore, this study was designed to investigate the association of
      the MRS score with postoperative survival and complications. MATERIAL/METHODS:
      Between 1989 and 2006, 115 patients were transplanted for histologically proven
      PBC at the Charite Campus Virchow Clinic. In 98 of these patients, MRS data was
      available and retrospectively analyzed. Median age of 87 women and 11 men was 54
      years (25 to 66 years). RESULTS: The median follow-up after liver transplantation
      was 109 months (0.5-205 months). Actuarial patient survival after 5, 10 and 15
      years was 90%, 88%, and 83%. Calculated survival by MRS without transplantation
      after 1, 5 and 7 years was 20%, 2% and 1% for these patients. Twelve patients
      (12%) died and histological recurrence of PBC was detected in 14 patients (14%).
      Seven patients underwent retransplantation (7%) and 58 patients developed an
      acute rejection episode (59%). Mean MRS was in all patients 9.54+/-1.35 and did
      not differ between patients with lethal course, retransplantations, PBC
      recurrence, rejection episodes and duration of hospital stay. Classification of
      all patients into a low (<8.5), middle (8.5-10) and high MRS score (>10) did not
      show a significant difference in long-term survival. Univariate analysis for
      identifying the level of MRS as risk for death, PBC-recurrence,
      retransplantation, acute rejection episodes and hospital stay only showed a
      significant increased risk for acute rejection episodes (1 episode = 0.04; 2
      episodes = 0.01) for patients with a MRS above 8.5. CONCLUSIONS: The Mayo risk
      score is an approved mathematical model predicting survival in non-transplanted
      patients suffering from PBC. However, the score did not predict the course of our
      liver transplanted patients in a long-term follow-up. We could not demonstrate a
      reduced patient survival at a median MRS of 9.4 and about 10.0. Therefore, it is,
      from our point of view, questionable if the optimal time point for OLT is still
      7.8.

PMID- 18806734
TI  - Immunogenicity of pneumococcal vaccination in renal transplant recipients and
      hemodialysis patients: a comparative controlled trial.
AB  - BACKGROUND: The objectives of this study were: to assess and compare the antibody
      responses of renal allograft recipients and dialysis patients to pneumococcal
      vaccination. MATERIAL/METHODS: 14 stable dialysis patients as well as 37 kidney
      transplant recipients were eligible for inclusion in this trial. Participated
      patients receive a single 0.5-mL of 23-valent vaccine Pneumovax administered
      intramuscularly in the upper extremities. The efficacy of vaccination was
      evaluated by measuring the antibody response to the whole vaccine. Sera were
      obtained prior to vaccination and 4 weeks, 6 months and 1 year after the
      vaccination. RESULTS: Prior to vaccination, mean IgG and IgG2 titers were
      equivalent in Dx and KTx patients (p>0.1 in both). Four weeks after vaccination,
      49 out of 51 participated patients (96%) represented an increase in their anti
      pneumococcal IgG levels (mean 99+/-66) compared to 48 out of 51 (94%) for month 6
      (mean 90+/-59), and 38 out of 45 (85%) for the first year after vaccination (mean
      73+/-69). KTx patients kept significantly more serum IgG2 levels at months 6 and
      12 after vaccination (p=0.001, p=0.03, respectively; Table 1). Mean IgG values
      for month 6 was 9+/-41 units lesser than month 1 post vaccination serum IgG
      levels. CONCLUSIONS: We found that patients with renal failure on hemodialysis
      and kidney transplantation well respond to immunization by anti pneumococcal
      vaccination. But, they rapidly loss their serum antibody levels during the one
      year after vaccination. Specifying protective levels for serum IgG and IgG2
      levels in these patients would help us to more precisely follow these patients
      and to consider a revaccination when they failed to save the protective serum
      antibody level.

PMID- 18806735
TI  - [Selected mechanisms of the therapeutic effect of arsenic trioxide in cancer
      treatment].
AB  - The properties of arsenic trioxide (arsenic) have been known for centuries. This
      compound has been used, among others, in the industrial production of paints and
      glass and also for the conservation of leather and wood. Although arsenic
      trioxide is highly toxic, this compound was shown to have a therapeutic potential
      as early as the fifteenth century. The period between the seventeenth and
      nineteenth centuries resulted in the development of new arsenic-based drugs which
      were applied for the treatment of skin diseases and acute promyelocytic leukemia.
      The mechanism of action of arsenic trioxide is mainly related to the induction of
      apoptosis (programmed cell death) in cancer cells. In particular it involves
      effects on the activities of JNK kinases, NF-kB transcription factor,
      glutathione, caspases, as well as pro- and anti-apoptotic proteins. Experiments
      investigating the effect of arsenic trioxide on cell lines such as glioma and
      prostate, breast, stomach, liver, and ovarian cancer are in progress. There are
      also clinical trials underway aimed at the use of arsenic trioxide with ascorbic
      acid, retinoid acid, and growth factors in combined therapy.

PMID- 18806736
TI  - [Dose rate-dependent cellular and molecular effects of ionizing radiation].
AB  - The aim of radiation therapy is to kill tumor cells while minimizing damage to
      normal cells. The ultimate effect of radiation can be apoptotic or necrotic cell
      death as well as cytogenetic damage resulting in genetic instability and/or cell
      death. The destructive effects of radiation arise from direct and indirect
      ionization events leading to peroxidation of macromolecules, especially those
      present in lipid-rich membrane structures as well as chromatin lipids. Lipid
      peroxidative end-products may damage DNA and proteins. A characteristic feature
      of radiation-induced peroxidation is an inverse dose-rate effect (IDRE), defined
      as an increase in the degree of oxidation(at constant absorbed dose) accompanying
      a lower dose rate. On the other hand, a low dose rate can lead to the
      accumulation of cells in G2, the radiosensitive phase of the cell cycle since
      cell cycle control points are not sensitive to low dose rates. Radiation dose
      rate may potentially be the main factor improving radiotherapy efficacy as well
      as affecting the intensity of normal tissue and whole-body side effects. A better
      understanding of dose rate-dependent biological effects may lead to improved
      therapeutic intervention and limit normal tissue reaction. The study reviews
      basic biological effects that depend on the dose rate of ionizing radiation.

PMID- 18806737
TI  - [The neuroprotective effect of PACAP, VIP, and derivatives in brain ischemia].
AB  - Nowadays, stroke is the most frequent cause of adult disability and death of the
      elderly. In most cases, the etiology of stroke involves cerebral ischemia.
      Ischemia-induced changes in the brain tissue lead not only to its degeneration,
      but also to significant activation of cellular mechanisms which protect the
      affected cells from damage. One such mechanism is the expression of endogenous
      neuroprotective substances, for example pituitary adenylate cyclase-activating
      polypeptide (PACAP) and vasoactive intenstinal peptide (VIP), whose properties
      were investigated recently. PACAP and VIP are neuropeptides widely distributed in
      both the central nervous system and peripheral organs of various vertebrates.
      They display pleiotropic biological activity. An extremely strong neuroprotective
      potential of these peptides has been observed and confirmed in numerous animal
      models. The protective mechanism of PACAP and VIP involves many intracellular
      pathways, which can be generally classified into four categories of action:
      antiapoptotic, anti-inflammatory, metabolic, and modulation of gene expression.
      Numerous data provided by many research centers suggest that endo- and exogenous
      PACAP and VIP, as well as their synthetic derivatives, reveal considerable
      neuroprotective and anti-inflammatory potential, suggesting a possibility of
      their use as new therapeutic strategies in stroke treatment.

PMID- 18806738
TI  - Proteomic approaches in biological and medical sciences: principles and
      applications.
AB  - After the first introduction of the concept of "proteome" more than 10 years ago,
      large-scale studies of protein expression, localization, activities and
      interactions have gained an exponential increase of interest, leading to
      extensive research and technology development. Proteomics is expansively applied
      in many areas, ranging from basic research, various disease and malignant tumors
      diagnostic and biomarker discovery to therapeutic applications. Several
      proteomics approaches have been developed for protein separation and
      identification, and for the characterization of protein function and structure.
      Two-dimensional gel electrophoresis, chromatography, capillary electrophoresis
      and mass spectrometry have become the most used proteomics methods. These
      techniques are also under constant development. This review provides an overview
      of the main techniques and their combinations, used in proteomics. The emphasis
      is made on description of advantages and disadvantages of each technique, to
      navigate in selection of the best application for solving a specific problem.

PMID- 18806739
TI  - Image-based evaluation of tumor response to treatment: where is radiology today?
AB  - Oncological patient care requires long term follow-up in order to estimate
      effectiveness of existing and new treatment choices. Image-based assessment of
      whole body tumour burden is commonly used for that purpose. The WHO response
      criteria were established in 1979 proposing bi-dimensional tumor measurements.
      New RECIST guidelines appeared in 2000 relying on only the longest diameter (uni
      dimensional) measurements. Obviously, a change in tumour size is only one
      potential surrogate for therapy response which not necessarily reflects the
      biologic activity of the tumour or the effect of particular therapy. Thus, the
      evaluation of biological, metabolic or molecular properties of a tumor and its
      changes might be an attractive means to assess the response to therapy
      sensitively and early.

PMID- 18806740
TI  - Differential effects of low and high doses of Taxol in anaplastic thyroid cancer
      cells: possible implication of the Pin1 prolyl isomerase.
AB  - AIM: To study the molecular mechanisms of dose-dependent effects of an anticancer
      drug, Taxol, on the cell cycle machinery and apoptosis-related proteins in
      thyroid anaplastic cancer cell lines ARO and KTC-2. MATERIALS AND METHODS:
      Western blot analysis was used for the detection of various proteins and of their
      phosphorylated forms. RESULTS: Low dose of Taxol that cause apoptosis (25 nM)
      enhanced Rb protein phosphorylation, decreased the expression of cyclin-dependent
      kinase inhibitors p27(KIP1) and p21(WAF1) , and potentiated the accumulation of
      phosphorylated p53 and of the prolyl isomerase Pin1. High Taxol doses (100 and
      1000 nM) that cause necrosis-like cell death drastically decreased Pin1 level in
      both cell lines. CONCLUSION: Low doses of Taxol promoted G(1)/S transition, thus
      exhibiting mitogen-like effect. Drug-induced Pin1 accumulation could probably
      facilitate this transition and in parallel contribute to apoptosis via the
      p53/p73-dependent mechanism. At higher doses of Taxol, there was a dramatic
      decrease of Pin1 levels which may be a reason for G(2)/M cell cycle arrest.

PMID- 18806741
TI  - Epothilone B induces glioblastoma cell death via survivin down-regulation.
AB  - AIM: The clinical resistance of glioblastomas to chemotherapeutic agents can be
      attributed to drug efflux pumps, such as P-glycoprotein, which contributes to
      reduce drug efficacy. The present study examined the utility of epothilone B,
      which is not a substrate for P-glycoprotein, on glioblastoma cells. METHODS: In
      vitro methods with glioblastoma cells varying in p53 status were used to assess
      the efficacy of epothilone B to induce anti-neoplastic responses.
      Immunofluorescence and ELISA procedures were used to examine levels of tubulin
      and survivin in epothilone B treated glioblastoma cells, while acridine orange
      labeling was used to detect the mode of epothilone B induced cell death. RESULTS:
      A clinically achievable concentration of epothilone B induced a cytotoxic
      response in p53 mutant glioblastoma cells, as a consequence of survivin down
      regulation and tubulin redistribution, while a cytostatic response was observed
      in p53 null glioblastoma cells with a modest increase in survivin expression post
      epothilone B treatment. However, p53 wild-type glioblastoma cells did not sustain
      a positive anti-tumorigenic response to epothilone B. CONCLUSION: Epothilone B,
      induced positive differential responses in glioblastoma cells with abnormal p53
      status, but not in p53 wild-type cells. This suggests that epothilone B is a
      potential alternative to classic microtubule inhibiting agents (ie vincristine,
      paclitaxel) used to treat clinical glioblastomas with p53 mutations.

PMID- 18806742
TI  - hTERT gene expression levels and telomerase activity in drug resistant MCF-7
      cells.
AB  - AIM: Cancer cells and some highly proliferative normal cells can stabilize
      telomere lengths by telomerase, which adds hexameric repeats to the ends of
      linear chromosomes. In this study, the activity of telomerase reverse
      transcriptase (hTERT) and its gene expression levels were investigated in
      paclitaxel, docetaxel, vincristine and doxorubicin resistant human MCF-7 breast
      adenocarcinoma cells. MATERIALS AND METHODS: Resistant cell lines were developed
      by stepwise selection of cells (MCF-7/S) in increasing doses of paclitaxel (MCF
      7/Pac), docetaxel (MCF-7/Doc), vincristine (MCF-7/Vinc) and doxorubicin (MCF
      7/Dox). Antiproliferative effects of anticancer drugs were evaluated by XTT assay
      and IC 50 values for different drugs were determined from cell proliferation
      curves. Expression levels of hTERT gene in sensitive and resistant cells were
      analyzed by RT-PCR. TRAP-Silver Staining assay was used to evaluate telomerase
      activities in these cells. RESULTS: When drug resistant and sensitive MCF-7 cells
      were compared no significant differences were observed in hTERT expression levels
      and telomerase enzyme activities. CONCLUSION: This report demonstrates that drug
      resistance developed against paclitaxel, docetaxel, vincristine and doxorubicin
      in MCF-7 cells is independent of the expression of hTERT gene and telomerase
      activity.

PMID- 18806743
TI  - Expression patterns of murine beta-defensin-2 mRNA in Lewis lung carcinoma cells
      in vitro and in vivo.
AB  - AIM: To evaluate the anti-tumor activity of murine beta-defensin-2 (mBD-2)
      expression in vitro and in vivo. MATERIALS AND METHODS: Based on pcDNA3 vector,
      constructs containing mBD-2 cDNA coding mature defensin molecule (pcDNA3-mBD2),
      and Igk-mBD-2 insertion, coding secretory sequence plus mature defensin molecule
      (pcDNA3-Igk-mBD-2) were generated. Lewis lung carcinoma (3LL) cells were
      transfected in vitro with these plasmids and with blank pcDNA3 vector, and the
      proliferative rate and clonogenic ability of obtained cell lines cultivated in
      vitro were analyzed using (3)H-incorporation technique and colony formation in
      semi-soft medium, respectively. Expression of mBD-2 mRNA was studied by
      semiquantative RT-PCR analysis. Also, transfected cells were transplanted to C57B
      mice, and the patterns of tumor growth in vivo were analyzed by routine
      techniques. RESULTS: We have found out that in the 3LL cells transfected with
      pcDNA3-mBD-2 and pcDNA3-Igk-mBD-2, the expression of mBD-2 mRNA is significantly
      down regulated compared to wild-type cells and 3LL cells transfected with blank
      vector. The cells with suppressed mBD-2 expression differed from parental cells
      and cells transfected with blank vector by higher proliferation rate (p < 0.001)
      and higher clonogenic ability. The 3LL-mBD-2 and 3LL-Igk-mBD-2 cells that are
      transplanted to C57B mice gave rise to more aggressive tumors that possessed
      significantly higher growth rate (p < 0.01) than those that arise from wild-type
      3LL cells. CONCLUSION: The obtained results indicate the relation between mBD-2
      expession in 3LL cells and their proliferation rate and malignant phenotype, and
      also allow to hypothesize the possibility of regulation of mBD-2 mRNA expression
      in these cells by a feedback mechanism.

PMID- 18806744
TI  - Effects of PDT with 5-aminolevulinic acid and chitosan on Walker carcinosarcoma.
AB  - Porphyrins and new chitosan hydrogels based composites with porphyrins are used
      as active cytotoxic antitumor agents in photodynamic therapy (PDT). AIM: The
      present study evaluates the effects of photodynamic therapy (PDT) with 5
      aminolevulinic acid (5-ALA) and 5-ALA associated with chitosan (CS) using Walker
      carcinosarcoma in rats as experimental model. METHODS: The animals were
      irradiated with red light ( lambda = 685 nm, D = 50 J/cm(2), 15 min) 3 h after
      i.p. administration of 5-ALA (250 mg/kg b.w.) or a mixture of 5-ALA (250 mg/kg
      b.w.) and CS (1.5 mg/kg b.w.). The animals were sacrificed at 1, 3, 6, 24 h and
      14 days after the treatment. The effects of PDT were investigated by
      morphological studies, monitoring the 5-ALA induced protoporphyrin IX (Pp IX)
      level in tumor tissue and serum, MMP 2 and 9 (gelatinases) activity in tumor and
      malondialdehyde level (MDA), marker of the lipoperoxidation process, in tumor and
      serum. RESULTS: Zymography revealed an increased activity of MMP 2 in tumors from
      animals treated with 5-ALA PDT. PDT with 5-ALA induced a higher lipid
      peroxidation in tumor tissue compared with 5-ALA-CS. CS associated to 5 ALA PDT
      enhanced the accumulation of PS in tumors inducing earlier necrotic changes. In
      the same time CS reduced MMP 2 activity. CONCLUSION: Our results suggest that
      MMPs activation and oxygen reactive species are involved in PDT effects.

PMID- 18806745
TI  - Influence of teichoic acid from S. aureus on metabolic activity of macrophages
      and cytotoxic activity of splenocytes of mice bearing Lewis lung carcinoma.
AB  - AIM: To investigate the effect of teichoic acid (TA) from the cell wall of S.
      aureus on some indices of immunological reactivity in mice bearing Lewis lung
      carcinoma (LLC). METHODS: The teichoic acid at the doses of 1, 2 and 4 microg/g
      of body weight has been administered subcutaneously simultaneously with tumor
      cells transplantation and in 7 days. The cytotoxic activity of peritoneal
      macrophages has been assessed by NBT-test. The splenocyte cytotoxic activity
      against the LLC cells has been tested by flow cytometry. The evaluation of tumor
      infiltration by lymphoid cells was carried out as well. RESULTS: TA had no
      significant effect on oxidative metabolism of peritoneal macrophages in tumor
      bearing mice. Upon TA administration, the cytotoxic activity of splenocytes
      against the LLC cells has been augmented in a dose-dependent manner (at the TA
      dose of 4 microg/g, 2-fold decrease of tumor growth and metastasis has been
      registered) and leads to decreased tumor infiltration by mononuclear cells.
      CONCLUSION: TA caused a dose dependent inhibition of growth and metastasis of
      LLC. It was supposed that TA can influence the tumor grows by activation of
      splenocytes cytotoxic activity.

PMID- 18806746
TI  - Expression and polimorphism of IFN-gamma gene in patients with cervical cancer.
AB  - BACKGROUND: Cervical cancer, the second most common malignancy in women
      worldwide, is almost invariably associated with infection by human papillomavirus
      (HPV). However, although many women are infected with high-risk types of HPV,
      only a subset of infected women will ever develop cervical cancer. Several
      studies suggested that immunological components play a key role in the
      development of cervical cancer. Interferon gamma (IFN-gamma ) is a cytokine
      produced by activated T cells and natural killer (NK) cells that enhances
      cellular immune responses by increasing T-cell cytotoxicity and NK cell activity.
      AIM: To study single nucleotide polymorphism (SNP), T to A, located at the +874
      position and measure IFN-gamma messenger RNA (mRNA) at the tumor site. METHODS:
      DNA was isolated from peripheral blood of 200 patients with cervical cancer and
      200 healthy controls. The allele polymorphism at position +874 in the IFN-gamma
      gene was studied by ARMS-PCR (Amplification Refractory Mutation System) and
      measured IFN-gamma mRNA at the tumor site by means of a semi-quantitative
      polymerase chain reaction (sqRT-PCR) assay. RESULTS: It was observed that
      genotypes AT and AA + AT increase the risk of cervical cancer (OR = 3.3, 95% CI -
      2.05-5.2, P <or= 0.001 - OR = 2.9, 95% CI - 1.9-4.6, P <or= 0.001, respectively).
      In case of passive smokers same genotypes showed highly significant increased
      risk of cervical cancer (OR = 5.55, 95% CI = 2.77-11.19 - OR = 5.25, 95% CI =
      2.77-10, respectively). Thus, the sqRT-PCR reflected the similar level of mRNA
      expression of IFN- gamma gene in patients suffering from cervical carcinoma and
      healthy controls. CONCLUSION: This is the first study to provide an evidence for
      effecting of IFN-gamma gene on the risk of cervical cancer in north Indian
      population.

PMID- 18806747
TI  - Alterations of constitutive pericentromeric heterochromatin in lymphocytes of
      cancer patients and lymphocytes exposed to 5-azacytidine is associated with DNA
      hypomethylation.
AB  - BACKGROUND: DNA hypomethylation plays a key role in carcinogenesis. The malignant
      transformation of cells as well as tumor progression is accompanied with
      increasing DNA hypomethylation in cancer cells. Nevertheless, the evolution of
      dis-epigenetic genomic alteration in the somatic cellular malignant
      transformation has not yet been clear. AIM: To study the relationship between the
      pattern of genomic DNA hypomethylation and DNA hyperploidy. METHODS: The model of
      5-azacytidine demethylating DNA treatment of the mitogen-stimulated lymphocytes
      in parallel with patients with solid cancer has been explored. DNA content was
      measured by quantitative DAPI and Hoechst 33258 fluorescence in situ
      hybridization on interphase nuclei. The conventional mitogen-stimulated blood
      lymphocyte culture development was performed in metaphase chromosomes and
      interphase nuclei assay. The light and fluorescent cytomorphological microscopy
      was performed. RESULTS: The model 5-azacytidine induced DNA demethylation results
      in increased DNA hyperploidy accompanying major pericentromeric heterochromatin
      (Alu) DNA repeats amplification similar to those during DNA hypomethylation
      associated cancer events, and both contributed to nuclear heteropycnosis
      development. The constitutive pericentromeric heterochromatin consequent
      morphological disturbance to the latent polytene chromomerization and
      heteropycnosis development both in cancer patients and in model 5-azacytidine
      exposured lymphocytes are associated with DNA hypomethylation. CONCLUSION: We
      have observed that the induced global DNA hypomethylation triggers dis-epigenetic
      morphological reprogramming of constitutive pericentromeric heterochromatin on
      the extrachromosomal organization pathway as seen during the heterochromatin
      latent polytene features development, which is of importance as one of the
      mechanism involving DNA hypomethylation in initiation and progression of cancer.

PMID- 18806748
TI  - Relation between cell-to-cell adhesion and angiogenesis and clinico-morphological
      prognostic factors in patients with gastric cancer.
AB  - AIM: To study the relation between the expression of the molecules of cell-to
      cell adhesion (E-cadherin, alpha- and beta-catenins) and vascular endothelial
      growth factor (VEGF) and traditional clinico-morphological characteristics of
      tumors to evaluate their prognostic value in the patients with gastric cancer.
      METHODS: To analyze the expression of E-cadherin, alpha- and beta-catenins, and
      VEGF the paraffin embedded tumor samples were studied by immunohistochemical
      analysis with the use of respective monoclonal antibodies. RESULTS: The presence
      of E-cadherin in tumors correlated with the absence of metastases in regional
      lymph nodes and was observed, as a rule, in the patients at the early stages of
      the disease. The presence of beta-catenin expression has been detected in gastric
      tumors of the patients without distant metastases, while the level of VEGF
      expression correlated with the degree of gastric wall injury. It has been
      demonstrated that the expression of E-cadherin and alpha-catenin is associated
      with favourable disease course and is a characteristic pattern for early stages
      of gastric cancer of intestinal type. However, VEGF expression is typical for the
      late stages of gastric cancer of diffuse type and is associated with poor
      prognosis. CONCLUSION: At the base of combined clinical, histological and
      immunohistochemical analysis of gastric tumors it has been shown that E-cadherin,
      alpha-catenin and VEGF could be used as informative markers of the disease
      course.

PMID- 18806749
TI  - Helper T cells (CD3 + /CD4 + ) within the autologous peripheral blood stem cell
      graft positively correlate with event free survival of multiple myeloma patients.
AB  - BACKGROUND: The microenvironment in the bone marrow - including lymphocytes - is
      part of the pathophysiology of multiple myeloma (MM). High dose chemotherapy
      followed by autologous stem cell transplantation is standard of care for younger
      patients. AIM: To determine the influence of reinfused lymphocyte subsets on
      event free survival (EFS) and overall survival (OS). METHODS: In peripheral blood
      (PB) and aphaeresis products (AP) of 41 MM patients lymphocyte subsets were
      determined by flow cytometry and were correlated with clinical outcome. RESULTS:
      PB lymphocyte subsets did not influence EFS or OS. Residual plasma cells in the
      AP were not correlated with poor outcome, whereas a high percentage of B cells
      (CD19+) showed a trend towards reduced EFS (P = 0.051). A high amount of CD4
      cells and an increased CD4/CD8 ratio were significantly associated with prolonged
      EFS. In contrast, high percentage of HLA-DR positive lymphocytes showed negative
      impact on EFS and OS (P = 0.03 and 0.02, respectively). CONCLUSION: Obtained data
      suggest the non-activated (HLA-DR negative) helper CD4+ T cells in the AP to be
      tumour protective.

PMID- 18806750
TI  - Activity and content of antioxidant enzymes in prostate tumors.
AB  - AIM: To investigate the antioxidant enzyme system in blood of men with benign
      hyperplasia of prostate (BHP) and with prostate adenocarcinoma (CaP). METHODS:
      The spectrophotometrical methods were applied to study content and activity
      changes of superoxide-dismutase (SOD), catalase (CAT), ceruloplasmin (Cp),
      tripeptide glutathione (GSH), glutathione-peroxidase (GSH-Px), and glutathione
      reductase (GR). Lipid peroxidation was evaluated using thiobarbituric acid (TBA)
      test. Blood plasma and erythrocytes of men with prostate tumors served as the
      material for the studies; n = 15 for each group. RESULTS: SOD activity was
      increased in BHP (24.65 +/- 1.20 U/microl) and decreased in CaP (11.45 +/- 0.89
      U/microl), CAT activity remained unaltered in BHP (12.41 +/- 0.85 mcat/ml) and
      was slightly declined in CaP (9.52 +/- 0.56 mcat/ml). Cp was increased in both
      kind of tumors, especially in CaP (54.27 +/- 7.22 mg%), as well as GSH (0.736 +/-
      0.07 microM/l) and GR (0.031 +/- 0.002 microM/g.Hemogl/min). GSH-Px was sharply
      increased in BHP (0.67 +/- 0.05 microM/g.Hemogl/min) and reduced in CaP (0.16 +/-
      0.01 microM/g.Hemogl/min). CONCLUSION: The development of BHP reflects relatively
      weakly on blood system as activity and content of antioxidant enzymes are not
      revealing marked changes in this disease. The significant changes are revealed in
      case of CaP, showing the reduced functional state of blood antioxidant enzyme
      system.

PMID- 18806751
TI  - Expression of MDR1, LRP, BCRP and Bcl-2 genes at diagnosis of childhood all:
      comparison with MRD status after induction therapy.
AB  - AIM: to investigate properties of leukemic cells by sorting out children
      diagnosed with ALL with different response to chemotherapy based on MRD level.
      METHODS: We used a minimal residual disease (MRD) data on day 36 obtained with 3
      colour flow cytometry as a reference. In view of MRD results, we used real-time
      PCR to assess expression levels of multidrug resistance associated genes MDR1,
      LRP and BCRP, antiapoptotic gene Bcl-2 in initial samples from children diagnosed
      with ALL. P-gp expression and function in initial samples were analyzed by flow
      cytometry. RESULTS: Briefly, medians of relative expression levels of MDR1 gene
      were roughly comparable and in MRD(+) group came to 22.8 (0.02-26.6; n = 9) vs
      24.8 (3.9-41.4; n = 10) in MRD(-) group. Bcl-2 gene showed tendency to higher
      expression levels in MRD(+) group with median at 5992.9 (521.0-10362.0; n = 9)
      compared to 3183.6 (1947.9-6581.0; n = 10) in MRD(-) group. LRP gene relative
      expression levels were similar in both groups and came to 1934.9 (1500.7-3490.4;
      n = 9) and 1408.5 (665.5-2917.1; n = 10) in MRD + and MRD(-) groups,
      respectively. The median of BCRP expression levels in MRD + group was
      considerably lower than that in MRD - group, namely 76000.0 (48196.2-169230.8; n
      = 9) and 227967.2 (16683.7-422222.2; n = 10), respectively, but statistical
      analysis showed no significant difference for this parameter. CONCLUSION: We
      investigated expression of multidrug resistance genes MDR1, LRP and BCRP and
      antiapoptotic gene Bcl-2 in leukemic cells at diagnosis, and MRD level at the end
      of induction therapy, and could not find obvious relations between these
      parameters.

PMID- 18806752
TI  - No association between the Arg194Trp and Arg399Gln polymorphisms of the XRCC1
      gene and colorectal cancer risk and progression in a Polish population.
AB  - BACKGROUND: The risk of sporadic colorectal cancer can be associated with
      environmental and lifestyle factors that may be sources of physical and chemical
      carcinogens, modulated by products of many low penetrance genes. Polymorphisms of
      DNA repair genes may influence variation in individual DNA repair capacity, which
      is crucial for preventing genomic instability, which, in turn, may be associated
      with risk of cancer. XRCC1 is an essential protein for the base excision repair
      pathway which primarily deals with DNA base modifications, arisen spontaneously
      or as a consequence of the action of environmental factors. AIM: To perform a
      case-control study and test the association between two polymorphisms in the
      XRCC1 gene: Arg194Trp and Arg399Gln and colorectal cancer risk and progression.
      METHODS: Genotypes were determined in DNA from peripheral blood lymphocytes of
      100 colorectal cancer patients and 100 age, sex and ethnic-matched cancer-free
      controls by PCR RFLP. RESULTS: We found that both polymorphisms of the XRCC1 gene
      were not associated with risk and progession of colorectal cancer in a Polish
      population. Moreover, there was not such association form the Arg194Trp/Arg399Gln
      haplotypes. CONCLUSION: The Arg194Trp and Arg399Gln polymorphisms of the XRCC1
      gene may not be associated with colorectal cancer in Polish population.

PMID- 18806753
TI  - Pharmacogenetics in drug discovery and development: a translational perspective.
AB  - The ability to predict a patient's drug response on the basis of their genetic
      information is expected to decrease attrition during the development of new,
      innovative drugs, and reduce adverse events by being able to predict individual
      patients at risk. Most pharmacogenetic investigations have focused on drug
      metabolism genes or candidate genes that are thought to be involved in specific
      diseases. However, robust new genetic tools now enable researchers to carry out
      multi-candidate gene-association and genome-wide studies for target discovery and
      drug development. Despite the expanding role of pharmacogenetics in industry,
      however, there is a paucity of published data. New forms of effective and
      efficient collaboration between industry and academia that may enhance the
      systematic collection of pharmacogenetic data are necessary to establish genetic
      profiles related to drug response, confirm pharmacogenetic associations and
      expedite the development of new drugs and diagnostic tests.

PMID- 18806754
TI  - Role of Smac in cephalostatin-induced cell death.
AB  - Cephalostatin 1 is a natural compound isolated from a marine worm that induces
      apoptosis in tumor cells via an apoptosome-independent but caspase-9-dependent
      pathway and through an endoplasmic reticulum stress response that is accompanied
      by caspase-4 activation. Here, we show that cephalostatin evokes mitochondrial
      Smac (second mitochondria-derived activator of caspases) but not cytochrome c
      release in various carcinoma cell lines. We also show that Smac is critically
      involved in caspase-9 activation as evidenced by gene silencing experiments.
      Remarkably, caspase-2 appears to be a major target for cephalostatin-induced
      cytosolic Smac. Using biochemical and genetic inhibition experiments, we
      demonstrate that caspase-2 participates in the apoptotic machinery induced by
      cephalostatin. Cephalostatin-activated caspase-2 appears to act as initiator
      caspase and is not involved in the activation of caspase-9. Importantly,
      experiments immunoprecipitating PIDD (p53-induced protein with a DD), RAIDD (RIP
      associated ICH-1/CED-3-homologous protein with DD) and caspase-2 identify
      cephalostatin as an experimental drug that induces the formation of the
      PIDDosome. The bis-steroid cephalostatin proves to be both a helpful tool to
      investigate apoptotic signaling and a promising chemotherapeutic agent.

PMID- 18806755
TI  - DAP-kinase is a mediator of endoplasmic reticulum stress-induced caspase
      activation and autophagic cell death.
AB  - Damage to endoplasmic reticulum (ER) homeostasis that cannot be corrected by the
      unfolded protein response activates cell death. Here, we identified death
      associated protein kinase (DAPk) as an important component in the ER stress
      induced cell death pathway. DAPk-/- mice are protected from kidney damage caused
      by injection of the ER stress-inducer tunicamycin. Likewise, the cell death
      response to ER stress-inducers is reduced in DAPk-/- primary fibroblasts. Both
      caspase activation and autophagy induction, events that are activated by ER
      stress and precede cell death, are significantly attenuated in the DAPk null
      cells. Notably, in this cellular setting, autophagy serves as a second cell
      killing mechanism that acts in concert with apoptosis, as the depletion of Atg5
      or Beclin1 from fibroblasts significantly protected from ER stress-induced death
      when combined with caspase-3 depletion. We further show that ER stress promotes
      the catalytic activity of DAPk by causing dephosphorylation of an inhibitory
      autophosphorylation on Ser(308) by a PP2A-like phosphatase. Thus, DAPk
      constitutes a critical integration point in ER stress signaling, transmitting
      these signals into two distinct directions, caspase activation and autophagy,
      leading to cell death.

PMID- 18806756
TI  - An increase in intracellular Ca2+ is required for the activation of mitochondrial
      calpain to release AIF during cell death.
AB  - Apoptosis-inducing factor (AIF), a flavoprotein with NADH oxidase activity
      anchored to the mitochondrial inner membrane, is known to be involved in complex
      I maintenance. During apoptosis, AIF can be released from mitochondria and
      translocate to the nucleus, where it participates in chromatin condensation and
      large-scale DNA fragmentation. The mechanism of AIF release is not fully
      understood. Here, we show that a prolonged ( approximately 10 min) increase in
      intracellular Ca(2+) level is a prerequisite step for AIF processing and release
      during cell death. In contrast, a transient ATP-induced Ca(2+) increase, followed
      by rapid normalization of the Ca(2+) level, was not sufficient to trigger the
      proteolysis of AIF. Hence, import of extracellular Ca(2+) into staurosporine
      treated cells caused the activation of a calpain, located in the intermembrane
      space of mitochondria. The activated calpain, in turn, cleaved membrane-bound
      AIF, and the soluble fragment was released from the mitochondria upon outer
      membrane permeabilization through Bax/Bak-mediated pores or by the induction of
      Ca(2+)-dependent mitochondrial permeability transition. Inhibition of calpain, or
      chelation of Ca(2+), but not the suppression of caspase activity, prevented
      processing and release of AIF. Combined, these results provide novel insights
      into the mechanism of AIF release during cell death.

PMID- 18806757
TI  - WW domain-containing E3 ubiquitin protein ligase 1 targets p63 transcription
      factor for ubiquitin-mediated proteasomal degradation and regulates apoptosis.
AB  - WWP1 E3 ubiquitin ligase has previously been shown to be frequently amplified and
      overexpressed in prostate and breast cancers. However, the mechanism of WWP1
      action is still largely unknown. p63, a member of the p53 family of transcription
      factors, has an important function in tumor development by regulating apoptosis.
      Using alternative promoters, p63 can be expressed as DeltaNp63 and TAp63.
      Increasing evidence suggests that TAp63 sensitizes cells to apoptosis but
      DeltaNp63 has an opposite function. In this study, we show that WWP1 binds,
      ubiquitinates, and destructs both DeltaNp63alpha and TAp63alpha. The protein
      protein interaction occurs between the PY motif of p63 and the WW domains of
      WWP1. The knockdown of WWP1 by siRNA increases the endogenous DeltaNp63alpha
      level in the MCF10A and 184B5 immortalized breast epithelial cell lines and
      confers resistance to doxorubicin-induced apoptosis. On the other hand, the
      knockdown of WWP1 increases the endogenous level of TAp63alpha, induces
      apoptosis, and increases sensitivity to doxorubicin and cisplatin in the HCT116
      colon cancer cell line in a p53-independent manner. Finally, we found that DNA
      damage chemotherapeutic drugs induce WWP1 mRNA and protein expression in a p53
      dependent manner. These data suggest that WWP1 may have a context-dependent role
      in regulating cell survival through targeting different p63 proteins for
      degradation.

PMID- 18806758
TI  - Bcl-2 inhibitors: small molecules with a big impact on cancer therapy.
AB  - Despite tremendous advances over the last 15 years in understanding fundamental
      mechanisms of apoptosis, this has failed to translate into improved cancer
      therapy for patients. However, there may now be light at the end of this long
      tunnel. Antiapoptotic Bcl-2 family members may be divided into two subclasses,
      one comprising Bcl-2, Bcl-X(L) and Bcl-w and the other Mcl-1 and Bcl2A1.
      Neutralization of both subclasses is required for apoptosis induction. Solution
      of the structure of antiapoptotic Bcl-2 family proteins has led to the design of
      novel small molecule inhibitors. Although many such molecules have been
      synthesized, rigorous verification of their specificity has often been lacking.
      Further studies have revealed that many putative Bcl-2 inhibitors are not
      specific and have other cellular targets, resulting in non-mechanism based
      toxicity. Two notable exceptions are ABT-737 and a related orally active
      derivative, ABT-263, which bind with high affinity to Bcl-2, Bcl-X(L) and Bcl-w
      and may prove to be useful tools for mechanistic studies. ABT-263 is in early
      clinical trials in lymphoid malignancies, small-cell lung cancer and chronic
      lymphocytic leukemia, and some patients have shown promising results. In in vitro
      studies, primary cells from patients with various B-cell malignancies are
      exquisitely sensitive to ABT-737, exhibiting novel morphological features of
      apoptosis including marked outer mitochondrial membrane rupture.

PMID- 18806759
TI  - E2F1 controls alternative splicing pattern of genes involved in apoptosis through
      upregulation of the splicing factor SC35.
AB  - The transcription factor E2F1 has a key function during S phase progression and
      apoptosis. It has been well-demonstrated that the apoptotic function of E2F1
      involves its ability to transactivate pro-apoptotic target genes. Alternative
      splicing of pre-mRNAs also has an important function in the regulation of
      apoptosis. In this study, we identify the splicing factor SC35, a member of the
      Ser-Rich Arg (SR) proteins family, as a new transcriptional target of E2F1. We
      demonstrate that E2F1 requires SC35 to switch the alternative splicing profile of
      various apoptotic genes such as c-flip, caspases-8 and -9 and Bcl-x, towards the
      expression of pro-apoptotic splice variants. Finally, we provide evidence that
      E2F1 upregulates SC35 in response to DNA-damaging agents and show that SC35 is
      required for apoptosis in response to these drugs. Taken together, these results
      demonstrate that E2F1 controls pre-mRNA processing events to induce apoptosis and
      identify the SC35 SR protein as a key direct E2F1-target in this setting.

PMID- 18806760
TI  - Control of autophagy by oncogenes and tumor suppressor genes.
AB  - Multiple oncogenes (in particular phosphatidylinositol 3-kinase, PI3K; activated
      Akt1; antiapoptotic proteins from the Bcl-2 family) inhibit autophagy. Similarly,
      several tumor suppressor proteins (such as BH3-only proteins; death-associated
      protein kinase-1, DAPK1; the phosphatase that antagonizes PI3K, PTEN; tuberous
      sclerosic complex 1 and 2, TSC1 and TSC2; as well as LKB1/STK11) induce
      autophagy, meaning that their loss reduces autophagy. Beclin-1, which is required
      for autophagy induction acts as a haploinsufficient tumor suppressor protein, and
      other essential autophagy mediators (such as Atg4c, UVRAG and Bif-1) are bona
      fide oncosuppressors. One of the central tumor suppressor proteins, p53 exerts an
      ambiguous function in the regulation of autophagy. Within the nucleus, p53 can
      act as an autophagy-inducing transcription factor. Within the cytoplasm, p53
      exerts a tonic autophagy-inhibitory function, and its degradation is actually
      required for the induction of autophagy. The role of autophagy in oncogenesis and
      anticancer therapy is contradictory. Chronic suppression of autophagy may
      stimulate oncogenesis. However, once a tumor is formed, autophagy inhibition may
      be a therapeutic goal for radiosensitization and chemosensitization. Altogether,
      the current state-of-the art suggests a complex relationship between cancer and
      deregulated autophagy that must be disentangled by further in-depth
      investigation.

PMID- 18806762
TI  - Ocular air gun injuries: a one-year surveillance study in the UK and Eire (BOSU).
      2001-2002.
AB  - AIMS: The vulnerability of the eye means that ocular air gun injuries figure
      prominently in the medical literature. This Study reports the results of the
      first ocular air gun injury surveillance study. METHODS: Ocular air gun injuries
      were reported to the British Ophthalmic Surveillance Unit (BOSU; United Kingdom
      and Eire) for the period November 2001-December 2002 (13 months). Two
      questionnaires were used to collect demographic details, circumstances of injury,
      details of injuries, medical management and outcome. RESULTS: A total of 105
      initial and 99 follow-up questionnaires were returned. Eighty-six ocular air gun
      injuries occurred during the last 12 months of surveillance yielding a corrected,
      estimated incidence of 91-115 injuries/year. Injuries were most frequent in
      August/September, and 90% (95/105) of victims were men with mean age of 17.5
      years (74% under 18 years). In all, 40% (32/81) of injuries occurred at home and
      53% (43/81) in a public place. 23% (19/84) of injuries were deliberate, 66%
      (69/104) of injuries were severe and 20% (21/105) resulted in ruptured globes. In
      all, 54% (48/89) required hospital admission and 41 required surgery. A total of
      11% (12/105) of eyes were either enucleated or eviscerated. Final visual acuity
      was <or=counting fingers in 29% (26/91) but >6/12 (Snellen) in 65% (59/91).
      Moderate/significant cosmetic deformities were recorded in 10% (8/77) and
      restricted ocular movements in 5% (4/72). CONCLUSIONS: Ocular air gun injuries
      damage sight and leave lasting morbidity. The demographics and circumstances of
      injury are well documented with access to, and unsupervised use of, air guns,
      appearing the principal risks for injury.

PMID- 18806761
TI  - p47phox-deficient immune microenvironment signals dysregulate naive T-cell
      apoptosis.
AB  - The phagocyte NADPH oxidase is a multicomponent enzyme complex mediating
      microbial killing. We find that NADPH oxidase p47(phox)-deficient (p47(phox-/-))
      chronic granulomatous disease (CGD) mice develop lymph node hyperplasia even
      without obvious infection, where increased number of T and B lymphocytes is
      associated with increased percent of naive cells and a lower T : B cell ratio
      than wild type. Paradoxically, despite lymphoid hyperplasia in vivo, when
      lymphocytes are placed in culture, p47(phox-/-) CD8(+) lymphocytes progress more
      rapidly to apoptosis than wild type. This is associated in cultured p47(phox-/-)
      CD8(+) lymphocytes with the induction of proapoptotic Bim and Puma expression,
      increased mitochondrial outer membrane permeabilization and depressed Bcl-2
      expression. Addition of IL-7 to the culture partially corrects Bcl-2 levels in
      cultured p47(phox-/-) CD8(+) lymphocytes and improves the survival. Adding
      glucose oxidase to the culture to generate hydrogen peroxide along with IL-7
      further improves p47(phox-/-) CD8(+) lymphocyte survival, but only to 30% of wild
      type. We conclude that p47(phox-/-) CD8(+) lymphocytes have an intrinsic survival
      defect likely in part related to the oxidase deficiency, but in vivo in lymph
      nodes of CGD mice, there are microenvironmental factors yet to be delineated that
      suppress the progression of apoptosis and allow the accumulation of lymphocytes
      leading to lymphoid hyperplasia.

PMID- 18806763
TI  - Haemorrhagic pituitary tumour presenting with unilateral paracentral visual
      disturbance.

PMID- 18806764
TI  - LDL apheresis in the treatment of non-arteritic ischaemic optic neuropathy: a 6
      month follow-up study.
AB  - PURPOSE: Verify the recovery of visual capacity after the administration of a
      combination of LDL apheresis (LA) and conventional therapy (CT). Design,
      prospective and interventional case series. METHODS: 20 patients affected by
      NAION were randomly subdivided into two groups of 10 patients (Group 1 and Group
      2). Group 1 underwent three sessions of LA associated with CT, whereas group 2
      received only CT. At discharge and at the 6 months follow-up visit, assessment in
      both groups was made of the best corrected visual acuity (BCVA) and the
      computerised visual field (CVF), comparing the findings with those at admission
      in each patient. RESULTS: Only the mean deviation (MD) at CVF was statistically
      improved in group 1 as compared with group 2 at discharge, judged against the
      values at admission (-11.08+/-6.51 vs -16.53+/-10.03, P=0.039; -17+/-5.24 vs 
      14.14+/-9.42, respectively). However, this increase was not confirmed at 6 months
      (-16.83+/- -10.72, group 1; -13.56+/-3.60 group 2). CONCLUSION: In NAION, LA
      induced a short term improvement in the MD, but by 6 months this had disappeared.

PMID- 18806765
TI  - Rapid action of oestradiol against hydrogen peroxide-induced oxidative stress in
      cataractous lens epithelium: an in vitro study.
AB  - PURPOSE: To evaluate the short-term protective effects of oestradiol against
      damages because of oxidative stress in human lens epithelial cells (LECs).
      METHODS: The central zone of human lens epithelium was obtained from the cataract
      surgery and cultured in MEM culture medium. These cultured LECs were treated with
      17beta-oestradiol for varying time intervals from 1 to 5 min followed by
      treatment with H(2)O(2) (5 x 10(-6) M) in the culture medium. Catalase activity
      was measured to access the oxidative stress levels. RESULTS: LECs exposed to
      H(2)O(2) (5 x 10(-6) M) showed a fourfold increase in catalase activity (407.03+/
      89.11 U/microg protein) after 6 h when compared to cultured unexposed LECs
      (97.124+/-9.4 U/microg protein). When the cultured LECs were treated with
      oestradiol (5 x 10(-8) M) before H(2)O(2) treatment, the increase in catalase
      activity was inhibited, whereas simultaneous and post-treatments showed no
      effect. The catalase activity of LECs pretreated with oestradiol for 1, 2, 3, and
      5 min was 259.92+/-18.37, 200.24+/-14.39, 140.50+/-19.83, and 110.01+/-14.66,
      respectively (P<0.0001). CONCLUSION: Antioxidative enzymes are synthesized in
      response to the oxidative stress signal. Upon treatment with oestrogen catalase
      is not synthesized. The pretreatment time of oestrogen required for its
      antioxidative effect can be seen within 5 min indicating non-genomic mode of
      action of oestrogen.

PMID- 18806766
TI  - Oxidative stress and antioxidant status in older adults with early cataract.
AB  - PURPOSE: Oxidative stress and antioxidant status were determined in forty healthy
      men and postmenopausal women aged 50-70 years (F25, M15), who underwent
      concurrent eye examinations. METHODS: Blood samples were collected for analysing
      major well-known antioxidants by HPLC systems with UV and ECD detectors, total
      antioxidant performance using a fluorometry, lipid peroxidation determined by
      malondialdehyde using a HPLC system with a fluorescent detector and by total
      hydroxyoctadecadienoic acid (HODE) and F2-isoprotanes (8-iso-PGF(2alpha)) using
      GC-MS. RESULTS: Twenty-seven (F17, M10) of the 40 subjects were diagnosed to have
      early cataracts at the onset of the study, which were regarded as age appropriate
      lens opacities. There was no significant difference in plasma major antioxidants,
      total antioxidant performance, and lipid peroxidation determined by
      malondialdehyde as well as 8-iso-PGF(2alpha) between the groups with and without
      early cataract. However, isomers of 9- and 13-(Z,E)-HODE levels were
      significantly higher in subjects with early cataract as compared with those of
      non-cataract subjects (P<0.05). CONCLUSION: Our data suggest that subjects with
      early cataract are under increased systemic oxidative stress, which can be
      identified by a sensitive biomarker of lipid peroxidation, such as isomers of
      HODE.

PMID- 18806767
TI  - Effects of scan circle displacement in optical coherence tomography retinal nerve
      fibre layer thickness measurement: a RNFL modelling study.
AB  - OBJECTIVE: To study the effect of optical coherence tomography (OCT) scan circle
      displacement on retinal nerve fibre layer (RNFL) measurement errors using cubic
      spline models. METHODS: Forty-nine normal subjects were included in the analysis.
      In one randomly selected eye in each subject, RNFL thickness around the optic
      disc was measured by taking 16 circular scans of different sizes (scan radius
      ranged from 1 to 2.5 mm). The RNFL profile in each eye was constructed with a
      mathematical model using a smoothing spline approximation. Scan circle (diameter
      3.4 mm) RNFL measurements (total average, superior, nasal, inferior, and temporal
      RNFL thicknesses) obtained from eight directions (superior, superonasal, nasal,
      inferonasal, inferior, inferotemporal, temporal, and superotemporal) displaced at
      different distances (0.1, 0.2, 0.3, 0.4, 0.5, 0.6, and 0.7 mm) from the disc
      centre were then computed by a computer program and compared to the 'reference
      standard' where the scan circle is centred at the optic disc. RNFL measurement
      error was calculated as the absolute of (RNFL thickness(displaced) - RNFL
      thickness(reference standard)). RESULTS: The respective mean average, superior,
      nasal, inferior, and temporal RNFL measurement errors were 2.3+/-2.0, 4.9+/-4.5,
      4.1+/-3.8, 6.2+/-7.6, and 3.8+/-3.5 microm upon 0.1 mm scan circle displacement,
      and 12.1+/-11.4, 27.8+/-18.4, 21.7+/-18.6, 34.8+/-22.9, and 15.2+/-10.7 microm
      upon 0.7 mm scan circle displacement. Significant differences of average and
      quadrant RNFL thicknesses were evident between centred and displaced scan circle
      measurements (all with P<0.001). RNFL measurement error increased in a monotonic
      fashion with increasing distance away from the disc and the change was direction
      dependent. CONCLUSIONS: RNFL measurement error varies with the direction and
      distance of scan displacement. The superior and the inferior RNFL measurements
      are most vulnerable to scan displacement errors, whereas the average RNFL
      thickness is the least susceptible. Obtaining a well-centred scan is essential
      for reliable RNFL measurement in OCT.

PMID- 18806769
TI  - Assessment of central arterial blood pressure during exercise: is it
      reproducible?

PMID- 18806770
TI  - Adiposity-sensitive and adiposity-resistant hypertension?

PMID- 18806771
TI  - Statin therapy in ARAS: beyond cholesterol lowering.

PMID- 18806773
TI  - Conjugated action of two species-specific invasion proteins for fetoplacental
      listeriosis.
AB  - The ability to cross host barriers is an essential virulence determinant of
      invasive microbial pathogens. Listeria monocytogenes is a model microorganism
      that crosses human intestinal and placental barriers, and causes severe
      maternofetal infections by an unknown mechanism. Several studies have helped to
      characterize the bacterial invasion proteins InlA and InlB. However, their
      respective species specificity has complicated investigations on their in vivo
      role. Here we describe two novel and complementary animal models for human
      listeriosis: the gerbil, a natural host for L. monocytogenes, and a knock-in
      mouse line ubiquitously expressing humanized E-cadherin. Using these two models,
      we uncover the essential and interdependent roles of InlA and InlB in
      fetoplacental listeriosis, and thereby decipher the molecular mechanism
      underlying the ability of a microbe to target and cross the placental barrier.

PMID- 18806774
TI  - Self-renewal and expansion of single transplanted muscle stem cells.
AB  - Adult muscle satellite cells have a principal role in postnatal skeletal muscle
      growth and regeneration. Satellite cells reside as quiescent cells underneath the
      basal lamina that surrounds muscle fibres and respond to damage by giving rise to
      transient amplifying cells (progenitors) and myoblasts that fuse with myofibres.
      Recent experiments showed that, in contrast to cultured myoblasts, satellite
      cells freshly isolated or satellite cells derived from the transplantation of one
      intact myofibre contribute robustly to muscle repair. However, because satellite
      cells are known to be heterogeneous, clonal analysis is required to demonstrate
      stem cell function. Here we show that when a single luciferase-expressing muscle
      stem cell is transplanted into the muscle of mice it is capable of extensive
      proliferation, contributes to muscle fibres, and Pax7(+)luciferase(+)
      mononucleated cells can be readily re-isolated, providing evidence of muscle stem
      cell self-renewal. In addition, we show using in vivo bioluminescence imaging
      that the dynamics of muscle stem cell behaviour during muscle repair can be
      followed in a manner not possible using traditional retrospective histological
      analyses. By imaging luciferase activity, real-time quantitative and kinetic
      analyses show that donor-derived muscle stem cells proliferate and engraft
      rapidly after injection until homeostasis is reached. On injury, donor-derived
      mononucleated cells generate massive waves of cell proliferation. Together, these
      results show that the progeny of a single luciferase-expressing muscle stem cell
      can both self-renew and differentiate after transplantation in mice, providing
      new evidence at the clonal level that self-renewal is an autonomous property of a
      single adult muscle stem cell.

PMID- 18806775
TI  - Glycogen synthase kinase 3 in MLL leukaemia maintenance and targeted therapy.
AB  - Glycogen synthase kinase 3 (GSK3) is a multifunctional serine/threonine kinase
      that participates in numerous signalling pathways involved in diverse
      physiological processes. Several of these pathways are implicated in disease
      pathogenesis, which has prompted efforts to develop GSK3-specific inhibitors for
      therapeutic applications. However, before now, there has been no strong rationale
      for targeting GSK3 in malignancies. Here we report pharmacological, physiological
      and genetic studies that demonstrate an oncogenic requirement for GSK3 in the
      maintenance of a specific subtype of poor prognosis human leukaemia, genetically
      defined by mutations of the MLL proto-oncogene. In contrast to its previously
      characterized roles in suppression of neoplasia-associated signalling pathways,
      GSK3 paradoxically supports MLL leukaemia cell proliferation and transformation
      by a mechanism that ultimately involves destabilization of the cyclin-dependent
      kinase inhibitor p27(Kip1). Inhibition of GSK3 in a preclinical murine model of
      MLL leukaemia provides promising evidence of efficacy and earmarks GSK3 as a
      candidate cancer drug target.

PMID- 18806776
TI  - MicroRNAs to Nanog, Oct4 and Sox2 coding regions modulate embryonic stem cell
      differentiation.
AB  - MicroRNAs (miRNAs) are short RNAs that direct messenger RNA degradation or
      disrupt mRNA translation in a sequence-dependent manner. For more than a decade,
      attempts to study the interaction of miRNAs with their targets were confined to
      the 3' untranslated regions of mRNAs, fuelling an underlying assumption that
      these regions are the principal recipients of miRNA activity. Here we focus on
      the mouse Nanog, Oct4 (also known as Pou5f1) and Sox2 genes and demonstrate the
      existence of many naturally occurring miRNA targets in their amino acid coding
      sequence (CDS). Some of the mouse targets analysed do not contain the miRNA seed,
      whereas others span exon-exon junctions or are not conserved in the human and
      rhesus genomes. miR-134, miR-296 and miR-470, upregulated on retinoic-acid
      induced differentiation of mouse embryonic stem cells, target the CDS of each
      transcription factor in various combinations, leading to transcriptional and
      morphological changes characteristic of differentiating mouse embryonic stem
      cells, and resulting in a new phenotype. Silent mutations at the predicted
      targets abolish miRNA activity, prevent the downregulation of the corresponding
      genes and delay the induced phenotype. Our findings demonstrate the abundance of
      CDS-located miRNA targets, some of which can be species-specific, and support an
      augmented model whereby animal miRNAs exercise their control on mRNAs through
      targets that can reside beyond the 3' untranslated region.

PMID- 18806777
TI  - Acoel development indicates the independent evolution of the bilaterian mouth and
      anus.
AB  - Most bilaterian animals possess a through gut with a separate mouth and anus. It
      is commonly believed that during the transition from radial to bilateral
      symmetry, both openings evolved simultaneously by the lateral closure of a slit
      like blastopore. Molecular phylogenies however, place the acoel flatworms, which
      have only one opening to their digestive system, as the sister group to all
      remaining Bilateria. To address how this single body opening is related to the
      mouth and anus of the protostomes and deuterostomes, we studied the expression of
      genes involved in bilaterian foregut and hindgut patterning during the
      development of the acoel Convolutriloba longifissura. Here we show that the genes
      brachyury and goosecoid are expressed in association with the acoel mouth,
      suggesting that this single opening is homologous to the mouth of other
      bilaterians. In addition, we find that the genes caudal, orthopedia and brachyury
      which are expressed in various bilaterian hindguts-are expressed in a small
      region at the posterior end of the animal, separated from the anterior oral
      brachyury-expressing region by a dorsal domain of ectodermal bmp2/4 expression.
      These results contradict the hypothesis that the bilaterian mouth and anus
      evolved simultaneously from a common blastoporal opening, and suggest that a
      through gut might have evolved independently in different animal lineages.

PMID- 18806778
TI  - The pectoral fin of Panderichthys and the origin of digits.
AB  - One of the identifying characteristics of tetrapods (limbed vertebrates) is the
      presence of fingers and toes. Whereas the proximal part of the tetrapod limb
      skeleton can easily be homologized with the paired fin skeletons of
      sarcopterygian (lobe-finned) fish, there has been much debate about the origin of
      digits. Early hypotheses interpreted digits as derivatives of fin radials, but
      during the 1990s the idea gained acceptance that digits are evolutionary
      novelties without direct equivalents in fish fin skeletons. This was partly based
      on developmental genetic data, but also substantially on the pectoral fin
      skeleton of the elpistostegid (transitional fish/tetrapod) Panderichthys, which
      appeared to lack distal digit-like radials. Here we present a CT scan study of an
      undisturbed pectoral fin of Panderichthys demonstrating that the plate-like
      'ulnare' of previous reconstructions is an artefact and that distal radials are
      in fact present. This distal portion is more tetrapod-like than that found in
      Tiktaalik and, in combination with new data about fin development in basal
      actinopterygians, sharks and lungfish, makes a strong case for fingers not being
      a novelty of tetrapods but derived from pre-existing distal radials present in
      all sarcopterygian fish.

PMID- 18806779
TI  - Sae2, Exo1 and Sgs1 collaborate in DNA double-strand break processing.
AB  - DNA ends exposed after introduction of double-strand breaks (DSBs) undergo 5'-3'
      nucleolytic degradation to generate single-stranded DNA, the substrate for
      binding by the Rad51 protein to initiate homologous recombination. This process
      is poorly understood in eukaryotes, but several factors have been implicated,
      including the Mre11 complex (Mre11-Rad50-Xrs2/NBS1), Sae2/CtIP/Ctp1 and Exo1.
      Here we demonstrate that yeast Exo1 nuclease and Sgs1 helicase function in
      alternative pathways for DSB processing. Novel, partially resected intermediates
      accumulate in a double mutant lacking Exo1 and Sgs1, which are poor substrates
      for homologous recombination. The early processing step that generates partly
      resected intermediates is dependent on Sae2. When Sae2 is absent, in addition to
      Exo1 and Sgs1, unprocessed DSBs accumulate and homology-dependent repair fails.
      These results suggest a two-step mechanism for DSB processing during homologous
      recombination. First, the Mre11 complex and Sae2 remove a small
      oligonucleotide(s) from the DNA ends to form an early intermediate. Second, Exo1
      and/or Sgs1 rapidly process this intermediate to generate extensive tracts of
      single-stranded DNA that serve as substrate for Rad51.

PMID- 18806781
TI  - Paracrine Wingless signalling controls self-renewal of Drosophila intestinal stem
      cells.
AB  - In the Drosophila midgut, multipotent intestinal stem cells (ISCs) that are
      scattered along the epithelial basement membrane maintain tissue homeostasis by
      their ability to steadily produce daughters that differentiate into either
      enterocytes or enteroendocrine cells, depending on the levels of Notch activity.
      However, the mechanisms controlling ISC self-renewal remain elusive. Here we show
      that a canonical Wnt signalling pathway controls ISC self-renewal. The ligand
      Wingless (Wg) is specifically expressed in the circular muscles next to ISCs,
      separated by a thin layer of basement membrane. Reduced function of wg causes ISC
      quiescence and differentiation, whereas wg overexpression produces excessive ISC
      like cells that express high levels of the Notch ligand, Delta. Clonal analysis
      shows that the main downstream components of the Wg pathway, including Frizzled,
      Dishevelled and Armadillo, are autonomously required for ISC self-renewal.
      Furthermore, epistatic analysis suggests that Notch acts downstream of the Wg
      pathway and a hierarchy of Wg/Notch signalling pathways controls the balance
      between self-renewal and differentiation of ISCs. These data suggest that the
      underlying circular muscle constitutes the ISC niche, which produce Wg signals
      that act directly on ISCs to promote ISC self-renewal. This study demonstrates
      markedly conserved mechanisms regulating ISCs from Drosophila to mammals. The
      identification of the Drosophila ISC niche and the principal self-renewal signal
      will facilitate further understanding of intestinal homeostasis control and
      tumorigenesis.

PMID- 18806780
TI  - Innate immunity and intestinal microbiota in the development of Type 1 diabetes.
AB  - Type 1 diabetes (T1D) is a debilitating autoimmune disease that results from T
      cell-mediated destruction of insulin-producing beta-cells. Its incidence has
      increased during the past several decades in developed countries, suggesting that
      changes in the environment (including the human microbial environment) may
      influence disease pathogenesis. The incidence of spontaneous T1D in non-obese
      diabetic (NOD) mice can be affected by the microbial environment in the animal
      housing facility or by exposure to microbial stimuli, such as injection with
      mycobacteria or various microbial products. Here we show that specific pathogen
      free NOD mice lacking MyD88 protein (an adaptor for multiple innate immune
      receptors that recognize microbial stimuli) do not develop T1D. The effect is
      dependent on commensal microbes because germ-free MyD88-negative NOD mice develop
      robust diabetes, whereas colonization of these germ-free MyD88-negative NOD mice
      with a defined microbial consortium (representing bacterial phyla normally
      present in human gut) attenuates T1D. We also find that MyD88 deficiency changes
      the composition of the distal gut microbiota, and that exposure to the microbiota
      of specific pathogen-free MyD88-negative NOD donors attenuates T1D in germ-free
      NOD recipients. Together, these findings indicate that interaction of the
      intestinal microbes with the innate immune system is a critical epigenetic factor
      modifying T1D predisposition.

PMID- 18806782
TI  - Cortisone dissociates the Shaker family K+ channels from their beta subunits.
AB  - The Shaker family voltage-dependent potassium channels (Kv1) are expressed in a
      wide variety of cells and are essential for cellular excitability. In humans,
      loss-of-function mutations of Kv1 channels lead to hyperexcitability and are
      directly linked to episodic ataxia and atrial fibrillation. All Kv1 channels
      assemble with beta subunits (Kv betas), and certain Kv betas, for example Kv beta
      1, have an N-terminal segment that closes the channel by the N-type inactivation
      mechanism. In principle, dissociation of Kv beta 1, although never reported,
      should eliminate inactivation and thus potentiate Kv1 current. We found that
      cortisone increases rat Kv1 channel activity by binding to Kv beta 1. A crystal
      structure of the Kv beta-cortisone complex was solved to 1.82-A resolution and
      revealed novel cortisone binding sites. Further studies demonstrated that
      cortisone promotes dissociation of Kv beta. The new mode of channel modulation
      may be explored by native or synthetic ligands to fine-tune cellular
      excitability.

PMID- 18806783
TI  - Small-molecule inhibition of HIV-1 Vif.
AB  - The HIV-1 protein Vif, essential for in vivo viral replication, targets the human
      DNA-editing enzyme, APOBEC3G (A3G), which inhibits replication of retroviruses
      and hepatitis B virus. As Vif has no known cellular homologs, it is an
      attractive, yet unrealized, target for antiviral intervention. Although zinc
      chelation inhibits Vif and enhances viral sensitivity to A3G, this effect is
      unrelated to the interaction of Vif with A3G. We identify a small molecule, RN
      18, that antagonizes Vif function and inhibits HIV-1 replication only in the
      presence of A3G. RN-18 increases cellular A3G levels in a Vif-dependent manner
      and increases A3G incorporation into virions without inhibiting general
      proteasome-mediated protein degradation. RN-18 enhances Vif degradation only in
      the presence of A3G, reduces viral infectivity by increasing A3G incorporation
      into virions and enhances cytidine deamination of the viral genome. These results
      demonstrate that the HIV-1 Vif-A3G axis is a valid target for developing small
      molecule-based new therapies for HIV infection or for enhancing innate immunity
      against viruses.

PMID- 18806784
TI  - Links from complex spikes to local plasticity and motor learning in the
      cerebellum of awake-behaving monkeys.
AB  - The hypothesis of cerebellar learning proposes that complex spikes in Purkinje
      cells engage mechanisms of plasticity in the cerebellar cortex; in turn, changes
      in the cerebellum depress the simple-spike response of Purkinje cells to a given
      stimulus and cause the adaptive modification of a motor behavior. Many elements
      of this hypothesis have been supported by prior experiments, and correlations
      have been found [corrected] between complex spikes, simple-spike plasticity and
      behavior [corrected] during the learning process. We carried out a trial-by-trial
      analysis of Purkinje cell responses in awake-behaving monkeys and found evidence
      for a causal role for complex spikes in the induction of cerebellar plasticity
      during a simple motor learning task. We found that the presence of a complex
      spike on one learning trial was linked to a substantial depression of simple
      spike responses on the subsequent trial, at a time when behavioral learning was
      expressed.

PMID- 18806785
TI  - Improved visual sensitivity during smooth pursuit eye movements.
AB  - When we view the world around us, we constantly move our eyes. This brings
      objects of interest into the fovea and keeps them there, but visual sensitivity
      has been shown to deteriorate while the eyes are moving. Here we show that human
      sensitivity for some visual stimuli is improved during smooth pursuit eye
      movements. Detection thresholds for briefly flashed, colored stimuli were 16%
      lower during pursuit than during fixation. Similarly, detection thresholds for
      luminance-defined stimuli of high spatial frequency were lowered. These findings
      suggest that the pursuit-induced sensitivity increase may have its neuronal
      origin in the parvocellular retino-thalamic system. This implies that the visual
      system not only uses feedback connections to improve processing for locations and
      objects being attended to, but that a whole processing subsystem can be boosted.
      During pursuit, facilitation of the parvocellular system may reduce motion blur
      for stationary objects and increase sensitivity to speed changes of the tracked
      object.

PMID- 18806786
TI  - FMRFamide neuropeptides and acetylcholine synergistically inhibit egg-laying by
      C. elegans.
AB  - Egg-laying behavior of the Caenorhabditis elegans hermaphrodite is regulated by G
      protein signaling pathways. Here we show that the egg laying-defective mutant egl
      6(n592) carries an activating mutation in a G protein-coupled receptor that
      inhibits C. elegans egg-laying motor neurons in a G(o)-dependent manner. Ligands
      for EGL-6 are Phe-Met-Arg-Phe-NH(2) (FMRFamide)-related peptides encoded by the
      genes flp-10 and flp-17. flp-10 is expressed in both neurons and non-neuronal
      cells. The major source of flp-17 peptides is a pair of presumptive sensory
      neurons, the BAG neurons. Genetic analysis of the egl-6 pathway revealed that the
      EGL-6 neuropeptide signaling pathway functions redundantly with acetylcholine to
      inhibit egg-laying. The retention of embryos in the uterus of the C. elegans
      hermaphrodite is therefore under the control of a presumptive sensory system and
      is inhibited by the convergence of signals from neuropeptides and the small
      molecule neurotransmitter acetylcholine.

PMID- 18806787
TI  - Jade-1 inhibits Wnt signalling by ubiquitylating beta-catenin and mediates Wnt
      pathway inhibition by pVHL.
AB  - The von Hippel-Lindau protein pVHL suppresses renal tumorigenesis in part by
      promoting the degradation of hypoxia-inducible HIF-alpha transcription factors;
      additional mechanisms have been proposed. pVHL also stabilizes the plant
      homeodomain protein Jade-1, which is a candidate renal tumour suppressor that may
      correlate with renal cancer risk. Here we show that Jade-1 binds the oncoprotein
      beta-catenin in Wnt-responsive fashion. Moreover, Jade-1 destabilizes wild-type
      beta-catenin but not a cancer-causing form of beta-catenin. Whereas the well
      established beta-catenin E3 ubiquitin ligase component beta-TrCP ubiquitylates
      only phosphorylated beta-catenin, Jade-1 ubiquitylates both phosphorylated and
      non-phosphorylated beta-catenin and therefore regulates canonical Wnt signalling
      in both Wnt-off and Wnt-on phases. Thus, the different characteristics of beta
      TrCP and Jade-1 may ensure optimal Wnt pathway regulation. Furthermore, pVHL
      downregulates beta-catenin in a Jade-1-dependent manner and inhibits Wnt
      signalling, supporting a role for Jade-1 and Wnt signalling in renal
      tumorigenesis. The pVHL tumour suppressor and the Wnt tumorigenesis pathway are
      therefore directly linked through Jade-1.

PMID- 18806788
TI  - Targeting of the F-actin-binding protein drebrin by the microtubule plus-tip
      protein EB3 is required for neuritogenesis.
AB  - Interactions between dynamic microtubules and actin filaments (F-actin) underlie
      a range of cellular processes including cell polarity and motility. In growth
      cones, dynamic microtubules are continually extending into selected filopodia,
      aligning alongside the proximal ends of the F-actin bundles. This interaction is
      essential for neuritogenesis and growth-cone pathfinding. However, the molecular
      components mediating the interaction between microtubules and filopodial F-actin
      have yet to be determined. Here we show that drebrin, an F-actin-associated
      protein, binds directly to the microtubule-binding protein EB3. In growth cones,
      this interaction occurs specifically when drebrin is located on F-actin in the
      proximal region of filopodia and when EB3 is located at the tips of microtubules
      invading filopodia. When this interaction is disrupted, the formation of growth
      cones and the extension of neurites are impaired. We conclude that drebrin
      targets EB3 to coordinate F-actin-microtubule interactions that underlie
      neuritogenesis.

PMID- 18806789
TI  - Proof-by-synthesis of the transcriptional logic of mammalian circadian clocks.
AB  - Mammalian circadian clocks consist of complex regulatory loops mediated through-
      at least--morning, daytime and night-time DNA elements. To prove the
      transcriptional logic of mammalian clocks, we developed an in cellulo mammalian
      cell-culture system that allowed us to design and implement artificial
      transcriptional circuits. Here we show that morning activation and night-time
      repression can yield the transcriptional output during the daytime, and similarly
      that daytime activation and morning repression can yield night-time
      transcriptional output. We also observed that the diverse transcriptional outputs
      of other phases can be generated through the expression of simple combinations of
      transcriptional activators and repressors. These results reveal design principles
      not only for understanding the continuous transcriptional outputs observed in
      vivo but also for the logical construction of artificial promoters working at
      novel phases. Logical synthesis of artificial circuits, with an identified
      structure and observed dynamics, provides an alternative strategy applicable to
      the investigation of complex biological systems.

PMID- 18806790
TI  - Tracking the structural dynamics of proteins in solution using time-resolved wide
      angle X-ray scattering.
AB  - We demonstrate tracking of protein structural changes with time-resolved wide
      angle X-ray scattering (TR-WAXS) with nanosecond time resolution. We investigated
      the tertiary and quaternary conformational changes of human hemoglobin under
      nearly physiological conditions triggered by laser-induced ligand photolysis. We
      also report data on optically induced tertiary relaxations of myoglobin and
      refolding of cytochrome c to illustrate the wide applicability of the technique.
      By providing insights into the structural dynamics of proteins functioning in
      their natural environment, TR-WAXS complements and extends results obtained with
      time-resolved optical spectroscopy and X-ray crystallography.

PMID- 18806791
TI  - Building consensus spectral libraries for peptide identification in proteomics.
AB  - Spectral searching has drawn increasing interest as an alternative to sequence
      database searching in proteomics. We developed and validated an open-source
      software toolkit, SpectraST, to enable proteomics researchers to build spectral
      libraries and to integrate this promising approach in their data-analysis
      pipeline. It allows individual researchers to condense raw data into spectral
      libraries, summarizing information about observed proteomes into a concise and
      retrievable format for future data analyses.

PMID- 18806792
TI  - Imaging individual mRNA molecules using multiple singly labeled probes.
AB  - We describe a method for imaging individual mRNA molecules in fixed cells by
      probing each mRNA species with 48 or more short, singly labeled oligonucleotide
      probes. This makes each mRNA molecule visible as a computationally identifiable
      fluorescent spot by fluorescence microscopy. We demonstrate simultaneous
      detection of three mRNA species in single cells and mRNA detection in yeast,
      nematodes, fruit fly wing discs, and mammalian cell lines and neurons.

PMID- 18806793
TI  - The immunity-related GTPase Irgm1 promotes the expansion of activated CD4+ T cell
      populations by preventing interferon-gamma-induced cell death.
AB  - Mice deficient in the interferon-gamma (IFN-gamma)-inducible, immunity-related
      GTPase Irgm1 have defective host resistance to a variety of intracellular
      pathogens. This greater susceptibility to infection is associated with impaired
      IFN-gamma-dependent macrophage microbicidal activity in vitro. Here we show that
      Irgm1 also regulated the survival of mature effector CD4(+) T lymphocytes by
      protecting them from IFN-gamma-induced autophagic cell death. Mice deficient in
      both IFN-gamma and Irgm1 were 'rescued' from the lymphocyte depletion and greater
      mortality that occurs in mice singly deficient in Irgm1 after mycobacterial
      infection. Our studies identify a feedback mechanism in the T helper type 1
      response that limits the detrimental effects of IFN-gamma on effector T
      lymphocyte survival while promoting the antimicrobial functions of IFN-gamma.

PMID- 18806795
TI  - A canine DNM1 mutation is highly associated with the syndrome of exercise-induced
      collapse.
AB  - Labrador retrievers are the most common dog breed in the world, with over 200,000
      new kennel club registrations per year. The syndrome of exercise-induced collapse
      (EIC) in this breed is manifested by muscle weakness, incoordination and life
      threatening collapse after intense exercise. Using a genome-wide microsatellite
      marker scan for linkage in pedigrees, we mapped the EIC locus to canine
      chromosome 9. We then used SNP association and haplotype analysis to fine map the
      locus, and identified a mutation in the dynamin 1 gene (DNM1) that causes an
      R256L substitution in a highly conserved region of the protein. This first
      documented mammalian DNM1 mutation is present at a high frequency in the breed
      and is a compelling candidate causal mutation for EIC, as the dynamin 1 protein
      has an essential role in neurotransmission and synaptic vesicle endocytosis.

PMID- 18806796
TI  - Insights from retinitis pigmentosa into the roles of isocitrate dehydrogenases in
      the Krebs cycle.
AB  - Here we describe two families with retinitis pigmentosa, a hereditary
      neurodegeneration of rod and cone photoreceptors in the retina. Affected family
      members were homozygous for loss-of-function mutations in IDH3B, encoding the
      beta-subunit of NAD-specific isocitrate dehydrogenase (NAD-IDH, or IDH3), which
      is believed to catalyze the oxidation of isocitrate to alpha-ketoglutarate in the
      citric acid cycle. Cells from affected individuals had a substantial reduction of
      NAD-IDH activity, with about a 300-fold increase in the K(m) for NAD. NADP
      specific isocitrate dehydrogenase (NADP-IDH, or IDH2), an enzyme that catalyzes
      the same reaction, was normal in affected individuals, and they had no health
      problems associated with the enzyme deficiency except for retinitis pigmentosa.
      These findings support the hypothesis that mitochondrial NADP-IDH, rather than
      NAD-IDH, serves as the main catalyst for this reaction in the citric acid cycle
      outside the retina, and that the retina has a particular requirement for NAD-IDH.

PMID- 18806794
TI  - The Pristionchus pacificus genome provides a unique perspective on nematode
      lifestyle and parasitism.
AB  - Here we present a draft genome sequence of the nematode Pristionchus pacificus, a
      species that is associated with beetles and is used as a model system in
      evolutionary biology. With 169 Mb and 23,500 predicted protein-coding genes, the
      P. pacificus genome is larger than those of Caenorhabditis elegans and the human
      parasite Brugia malayi. Compared to C. elegans, the P. pacificus genome has more
      genes encoding cytochrome P450 enzymes, glucosyltransferases, sulfotransferases
      and ABC transporters, many of which were experimentally validated. The P.
      pacificus genome contains genes encoding cellulase and diapausin, and cellulase
      activity is found in P. pacificus secretions, indicating that cellulases can be
      found in nematodes beyond plant parasites. The relatively higher number of
      detoxification and degradation enzymes in P. pacificus is consistent with its
      necromenic lifestyle and might represent a preadaptation for parasitism. Thus,
      comparative genomics analysis of three ecologically distinct nematodes offers a
      unique opportunity to investigate the association between genome structure and
      lifestyle.

PMID- 18806797
TI  - Crystal structures of the SAM-III/S(MK) riboswitch reveal the SAM-dependent
      translation inhibition mechanism.
AB  - Three distinct classes of S-adenosyl-L-methionine (SAM)-responsive riboswitches
      have been identified that regulate bacterial gene expression at the levels of
      transcription attenuation or translation inhibition. The S(MK) box (SAM-III)
      translational riboswitch has been identified in the SAM synthetase gene in
      members of the Lactobacillales. Here we report the 2.2-A crystal structure of the
      Enterococcus faecalis S(MK) box riboswitch. The Y-shaped riboswitch organizes its
      conserved nucleotides around a three-way junction for SAM recognition. The Shine
      Dalgarno sequence, which is sequestered by base-pairing with the anti-Shine
      Dalgarno sequence in response to SAM binding, also directly participates in SAM
      recognition. The riboswitch makes extensive interactions with the adenosine and
      sulfonium moieties of SAM but does not appear to recognize the tail of the
      methionine moiety. We captured a structural snapshot of the S(MK) box riboswitch
      sampling the near-cognate ligand S-adenosyl-L-homocysteine (SAH) in which SAH was
      found to adopt an alternative conformation and fails to make several key
      interactions.

PMID- 18806798
TI  - Mapping a molecular link between allosteric inhibition and activation of the
      glycine receptor.
AB  - Cys-loop ligand-gated ion channels mediate rapid neurotransmission throughout the
      central nervous system. They possess agonist recognition sites and allosteric
      sites where modulators regulate ion channel function. Using strychnine-sensitive
      glycine receptors, we identified a scaffold of hydrophobic residues enabling
      allosteric communication between glycine-agonist binding loops A and D, and the
      Zn(2+)-inhibition site. Mutating these hydrophobic residues disrupted Zn(2+)
      inhibition, generating novel Zn(2+)-activated receptors and spontaneous channel
      activity. Homology modeling and electrophysiology revealed that these phenomena
      are caused by disruption to three residues on the '-' loop face of the Zn(2+)
      inhibition site, and to D84 and D86, on a neighboring beta3 strand, forming a
      Zn(2+)-activation site. We provide a new view for the activation of a Cys-loop
      receptor where, following agonist binding, the hydrophobic core and interfacial
      loops reorganize in a concerted fashion to induce downstream gating.

PMID- 18806799
TI  - A torque component present in mitotic kinesin Eg5 revealed by three-dimensional
      tracking.
AB  - Mitotic kinesin Eg5 is a homotetrameric molecular motor that cross-links and
      slides microtubules. The extent to which Eg5 moves processively is not clear.
      Here we use three-dimensional tracking of a quantum dot attached to the
      microtubule in a motility assay to directly visualize the corkscrew motion of a
      sliding microtubule. We show that the rotational pitch of microtubule sliding
      conveniently reports on the processivity of the driving motors, confirming that
      two-headed Eg5 is much less processive than two-headed kinesin-1.

PMID- 18806800
TI  - Structural model for strain-dependent microtubule activation of Mg-ADP release
      from kinesin.
AB  - Mg-ADP release is considered to be a crucial process for the regulation and
      motility of kinesin. To gain insight into the structural basis of this process,
      we solved the atomic structures of kinesin superfamily protein-1A (KIF1A) during
      and after Mg(2+) release. On the basis of new structural and mutagenesis data, we
      propose a model mechanism for microtubule activation of Mg-ADP release from
      KIF1A. In our model, a specific interaction between loop L7 of KIF1A and beta
      tubulin reconfigures the KIF1A active site by shifting the relative positions of
      switches I and II. This leads to the sequential release of a group of water
      molecules that sits over the Mg(2+) in the active site, followed by Mg(2+) and
      finally the ADP. We further propose that this set of events is linked to a strain
      dependent docking of the neck linker to the motor core, which produces a two-step
      power stroke.

PMID- 18806801
TI  - Inhibition of lipoprotein-associated phospholipase A2 reduces complex coronary
      atherosclerotic plaque development.
AB  - Increased lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) activity is
      associated with increased risk of cardiac events, but it is not known whether Lp
      PLA(2) is a causative agent. Here we show that selective inhibition of Lp-PLA(2)
      with darapladib reduced development of advanced coronary atherosclerosis in
      diabetic and hypercholesterolemic swine. Darapladib markedly inhibited plasma and
      lesion Lp-PLA(2) activity and reduced lesion lysophosphatidylcholine content.
      Analysis of coronary gene expression showed that darapladib exerted a general
      anti-inflammatory action, substantially reducing the expression of 24 genes
      associated with macrophage and T lymphocyte functioning. Darapladib treatment
      resulted in a considerable decrease in plaque area and, notably, a markedly
      reduced necrotic core area and reduced medial destruction, resulting in fewer
      lesions with an unstable phenotype. These data show that selective inhibition of
      Lp-PLA(2) inhibits progression to advanced coronary atherosclerotic lesions and
      confirms a crucial role of vascular inflammation independent from
      hypercholesterolemia in the development of lesions implicated in the pathogenesis
      of myocardial infarction and stroke.

PMID- 18806802
TI  - Cyclophilin D deficiency attenuates mitochondrial and neuronal perturbation and
      ameliorates learning and memory in Alzheimer's disease.
AB  - Cyclophilin D (CypD, encoded by Ppif) is an integral part of the mitochondrial
      permeability transition pore, whose opening leads to cell death. Here we show
      that interaction of CypD with mitochondrial amyloid-beta protein (Abeta)
      potentiates mitochondrial, neuronal and synaptic stress. The CypD-deficient
      cortical mitochondria are resistant to Abeta- and Ca(2+)-induced mitochondrial
      swelling and permeability transition. Additionally, they have an increased
      calcium buffering capacity and generate fewer mitochondrial reactive oxygen
      species. Furthermore, the absence of CypD protects neurons from Abeta- and
      oxidative stress-induced cell death. Notably, CypD deficiency substantially
      improves learning and memory and synaptic function in an Alzheimer's disease
      mouse model and alleviates Abeta-mediated reduction of long-term potentiation.
      Thus, the CypD-mediated mitochondrial permeability transition pore is directly
      linked to the cellular and synaptic perturbations observed in the pathogenesis of
      Alzheimer's disease. Blockade of CypD may be a therapeutic strategy in
      Alzheimer's disease.

PMID- 18806803
TI  - Divergent TLR7 and TLR9 signaling and type I interferon production distinguish
      pathogenic and nonpathogenic AIDS virus infections.
AB  - Pathogenic HIV infections of humans and simian immunodeficiency virus (SIV)
      infections of rhesus macaques are characterized by generalized immune activation
      and progressive CD4(+) T cell depletion. In contrast, natural reservoir hosts for
      SIV, such as sooty mangabeys, do not progress to AIDS and show a lack of aberrant
      immune activation and preserved CD4(+) T cell populations, despite high levels of
      SIV replication. Here we show that sooty mangabeys have substantially reduced
      levels of innate immune system activation in vivo during acute and chronic SIV
      infection and that sooty mangabey plasmacytoid dendritic cells (pDCs) produce
      markedly less interferon-alpha in response to SIV and other Toll-like receptor 7
      and 9 ligands ex vivo. We propose that chronic stimulation of pDCs by SIV and HIV
      in non-natural hosts may drive the unrelenting immune system activation and
      dysfunction underlying AIDS progression. Such a vicious cycle of continuous virus
      replication and immunopathology is absent in natural sooty mangabey hosts.

PMID- 18806804
TI  - How do detemir and glargine compare when added to oral agents in insulin-naive
      patients with type 2 diabetes mellitus?

PMID- 18806805
TI  - Does intensive glycemic control improve cardiovascular outcomes?

PMID- 18806806
TI  - Protective action of doxycycline against diabetic cardiomyopathy in rats.
AB  - BACKGROUND AND PURPOSE: Reactive oxygen and nitrogen species play an important
      role in the development of diabetic cardiomyopathy. They can activate matrix
      metalloproteinases (MMPs), and MMP-2 in particular is known to mediate early
      consequences of oxidative stress injury in the heart. Therefore, we investigated
      the role of MMP-2 and the effect of the MMP inhibitor doxycycline on the changes
      of heart function caused by diabetes. EXPERIMENTAL APPROACH: Using streptozotocin
      induced diabetic rats, we evaluated the effect of doxycycline on both mechanical
      and electrical function of isolated hearts, papillary muscle and cardiomyocytes.
      KEY RESULTS: Doxycycline abolished the diabetes-induced depression in left
      ventricular developed pressure and the rates of changes in developed pressure in
      isolated hearts and normalized the prolongation of the action potential in
      papillary muscles. In cardiomyocytes isolated from doxycycline-treated diabetic
      rats, the altered kinetic parameters of Ca(2+) transients, depressed Ca(2+)
      loading of sarcoplasmic reticulum and basal intracellular Ca(2+) level, and the
      spatio-temporal properties of Ca(2+) sparks were significantly restored. Gelatin
      zymography and western blot data indicated that the diabetes-induced alterations
      in MMP-2 activity and protein level, level of tissue inhibitor of matrix
      metalloproteinase-4 and loss of troponin I were restored to control levels with
      doxycycline. CONCLUSIONS AND IMPLICATIONS: Our data suggest that these beneficial
      effects of doxycycline on the mechanical, electrical and biochemical properties
      of the diabetic rat heart appear, at least in part, to be related to inhibition
      of MMP activity, implying a role for MMPs in the development of diabetic
      cardiomyopathy.

PMID- 18806807
TI  - Mono-galloyl glucose derivatives are potent poly(ADP-ribose) glycohydrolase
      (PARG) inhibitors and partially reduce PARP-1-dependent cell death.
AB  - BACKGROUND AND PURPOSE: Maintenance of poly(ADP-ribose) (PAR) polymers at
      homoeostatic levels by PAR glycohydrolase (PARG) is central in cell functioning
      and survival. Yet the pharmacological relevance of PARG inhibitors is still
      debated. Gallotannin, a complex mixture of hydrolysable tannins from oak gall,
      inhibits PARG but which of its constituents is responsible for the inhibition and
      whether the pharmacodynamic properties are due to its antioxidant properties, has
      not yet been established. EXPERIMENTAL APPROACH: A structure-activity
      relationship study was conducted on different natural and synthetic
      tannins/galloyl derivatives as potential PARG inhibitors, using a novel in vitro
      enzymic assay. Cytotoxicity was assayed in cultured HeLa cells. KEY RESULTS: Mono
      galloyl glucose compounds were potent inhibitors of PARG, with activities similar
      to that of ADP-(hydroxymethyl) pyrrolidinediol, the most potent PARG inhibitor
      yet identified. When tested on HeLa cells exposed to the PAR polymerase (PARP)-1
      activating compound 1-methyl-3-nitro-1-nitrosoguanidine (MNNG), 3-galloyl glucose
      weakly inhibited PAR degradation. Conversely, the more lipophilic, 3-galloyl-1,2
      O-isopropylidene glucose, despite being inactive on the pure enzyme, efficiently
      prolonged the half-life of the polymers in intact HeLa cells. Also, PARG
      inhibitors, but not radical scavengers, reduced, in part, cell death caused by
      MNNG. CONCLUSIONS AND IMPLICATIONS: Taken together, our findings identify mono
      galloyl glucose derivatives as potent PARG inhibitors, and emphasize the active
      function of this enzyme in cell death.

PMID- 18806808
TI  - Luteolin inhibits myelin basic protein-induced human mast cell activation and
      mast cell-dependent stimulation of Jurkat T cells.
AB  - BACKGROUND AND PURPOSE: Allergic inflammation and autoimmune diseases, such as
      atopic dermatitis, psoriasis and multiple sclerosis (MS), involve both mast cell
      and T-cell activation. However, possible interactions between the two and the
      mechanism of such activations are largely unknown. EXPERIMENTAL APPROACH: Human
      umbilical cord blood-derived cultured mast cells (hCBMCs) and Jurkat T cells were
      incubated separately or together, following activation with myelin basic protein
      (MBP), as well as with or without pretreatment with the flavonoid luteolin for 15
      min. The supernatant fluid was assayed for inflammatory mediators released from
      mast cells and interleukin (IL)-2 release from Jurkat cells. KEY RESULTS: MBP (10
      microM) stimulates hCBMCs to release IL-6, IL-8, transforming growth factor (TGF)
      beta1, tumour necrosis factor-alpha (TNF-alpha), vascular endothelial growth
      factor (VEGF), histamine and tryptase (n=6, P<0.05). Addition of mast cells to
      Jurkat cells activated by anti-CD3/anti-CD28 increases IL-2 release by 30-fold
      (n=3, P<0.05). MBP-stimulated mast cells and their supernatant fluid further
      increase Jurkat cell IL-2 release (n=3, P<0.05). Separation of mast cells and
      activated Jurkat cells by a Transwell permeable membrane inhibits Jurkat cell
      stimulation by 60%. Pretreatment of Jurkat cells with a TNF-neutralizing antibody
      reduces IL-2 release by another 40%. Luteolin pretreatment inhibits mast cell
      activation (n=3-6, P<0.05), Jurkat cell activation and mast cell-dependent Jurkat
      cell stimulation (n=3, P<0.05). CONCLUSIONS AND IMPLICATIONS: Mast cells can
      stimulate activated Jurkat cells. This interaction is inhibited by luteolin,
      suggesting that this flavonoid may be useful in the treatment of autoimmune
      diseases.

PMID- 18806810
TI  - On contemporaneous controls, unlikely outcomes, boxes and replacing the
      'Student': good statistical practice in pharmacology, problem 3.
AB  - This paper is intended to assist pharmacologists to make the most of statistical
      analysis and avoid common errors. A scenario, in which an experimenter performed
      an experiment in two separate stages, combined the control groups for analysis
      and found some surprising results, is presented. The consequences of combined
      controls are discussed, appropriate display and analysis of the data are
      described, and an analysis of the likelihood of erroneous conclusions is made.
      Comparisons between data from separately conducted experimental series are
      hazardous when there is any possibility that the properties of the experimental
      units have changed between the series. Experiments that have been performed
      independently should be analyzed independently. Unlikely or surprising results
      should be treated with caution and a high standard of evidence should be
      required, and verification by repeated experiments should be performed and
      reported. Box and whisker plots contain more information than plots more commonly
      used to display for qualitative variables and should be used where the sample
      size is large enough (say, n > or = 5). In most biomedical experiments the
      observations are not random samples from large populations as assumed by
      conventional parametric analyses such as Student's t-test, and so permutation
      tests, which do not lose their validity when a sampled population is non-normal
      or when the data are not random samples, should frequently be used instead of
      Student's t-tests.

PMID- 18806809
TI  - The pharmacological challenge to tame the transient receptor potential vanilloid
      1 (TRPV1) nocisensor.
AB  - The transient receptor potential vanilloid-1 (TRPV1) cation channel is a receptor
      that is activated by heat (>42 degrees C), acidosis (pH<6) and a variety of
      chemicals among which capsaicin is the best known. With these properties, TRPV1
      has emerged as a polymodal nocisensor of nociceptive afferent neurones, although
      some non-neuronal cells and neurones in the brain also express TRPV1. The
      activity of TRPV1 is controlled by a multitude of regulatory mechanisms that
      either cause sensitization or desensitization of the channel. As many proalgesic
      pathways converge on TRPV1 and this nocisensor is upregulated and sensitized by
      inflammation and injury, TRPV1 is thought to be a central transducer of
      hyperalgesia and a prime target for the pharmacological control of pain. As a
      consequence, TRPV1 agonists causing defunctionalization of sensory neurones and a
      large number of TRPV1 blockers have been developed, some of which are in clinical
      trials. A major drawback of many TRPV1 antagonists is their potential to cause
      hyperthermia, and their long-term use may carry further risks because TRPV1 has
      important physiological functions in the peripheral and central nervous system.
      The challenge, therefore, is to pharmacologically differentiate between the
      physiological and pathological implications of TRPV1. There are several
      possibilities to focus therapy specifically on those TRPV1 channels that
      contribute to disease processes. These approaches include (i) site-specific TRPV1
      antagonists, (ii) modality-specific TRPV1 antagonists, (iii) uncompetitive TRPV1
      (open channel) blockers, (iv) drugs interfering with TRPV1 sensitization, (v)
      drugs interfering with intracellular trafficking of TRPV1 and (vi) TRPV1 agonists
      for local administration.

PMID- 18806811
TI  - Low doses of alpha 2-adrenoceptor antagonists augment spinal morphine analgesia
      and inhibit development of acute and chronic tolerance.
AB  - BACKGROUND AND PURPOSE: Ultra-low doses of opioid receptor antagonists augment
      spinal morphine antinociception and block the induction of tolerance. Considering
      the evidence demonstrating functional and physical interactions between the
      opioid and alpha(2)-adrenoceptors, this study investigated whether ultra-low
      doses of alpha(2)-adrenoceptor antagonists also influence spinal morphine
      analgesia and tolerance. EXPERIMENTAL APPROACH: Effects of low doses of the
      competitive alpha(2)-adrenoceptor antagonists-atipamezole (0.08, 0.8 ng),
      yohimbine (0.02, 2 ng), mirtazapine (0.02 ng) and idazoxan (0.08 ng) were
      investigated on intrathecal morphine analgesia, as well as acute and chronic
      morphine antinociceptive tolerance using the rat tail flick and paw pressure
      tests. KEY RESULTS: At doses markedly lower than those producing alpha(2)
      adrenoceptor blockade, atipamezole, yohimbine, mirtazapine and idazoxan,
      prolonged the antinociceptive effects of morphine. When co-administered with
      repeated acute spinal injections of morphine, all four agents blocked the
      induction of acute tolerance. Co-injection of atipamezole with morphine for 5
      days inhibited the development of tolerance in a chronic treatment paradigm.
      Spinal administration of atipamezole also reversed established antinociceptive
      tolerance to morphine as indicated by the restoration of morphine antinociceptive
      potency. The effects of atipamezole on spinal morphine tolerance were not
      influenced by treatment with 6-hydroxydopamine. CONCLUSIONS AND IMPLICATIONS: Low
      doses of competitive alpha(2)-adrenoceptor antagonists can augment acute morphine
      analgesia and block or reverse tolerance to spinal administration of morphine.
      These actions are interpreted in terms of their interaction with an opioid
      alpha(2)-adrenoceptor complex, whose activity may have a function in the genesis
      of analgesic tolerance.

PMID- 18806812
TI  - Benzylidene derivatives of andrographolide inhibit growth of breast and colon
      cancer cells in vitro by inducing G(1) arrest and apoptosis.
AB  - BACKGROUND AND PURPOSE: Andrographolide, the major phytoconstituent of
      Andrographis paniculata, was previously shown by us to have activity against
      breast cancer. This led to synthesis of new andrographolide analogues to find
      compounds with better activity than the parent compound. Selected benzylidene
      derivatives were investigated for their mechanisms of action by studying their
      effects on the cell cycle progression and cell death. EXPERIMENTAL APPROACH:
      Microculture tetrazolium, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium
      bromide (MTT) and sulphorhodamine B (SRB) assays were utilized in assessing the
      in vitro growth inhibition and cytotoxicity of compounds. Flow cytometry was used
      to analyse the cell cycle distribution of control and treated cells. CDK1 and
      CDK4 levels were determined by western blotting. Apoptotic cell death was
      assessed by fluorescence microscopy and flow cytometry. KEY RESULTS: Compounds,
      in nanomolar to micromolar concentrations, exhibited growth inhibition and
      cytotoxicity in MCF-7 (breast) and HCT-116 (colon) cancer cells. In the NCI
      screen, 3,19-(2-bromobenzylidene) andrographolide (SRJ09) and 3,19-(3-chloro-4
      fluorobenzylidene) andrographolide (SRJ23) showed greater cytotoxic potency and
      selectivity than andrographolide. SRJ09 and SRJ23 induced G(1) arrest and
      apoptosis in MCF-7 and HCT-116 cells, respectively. SRJ09 downregulated CDK4 but
      not CDK1 level in MCF-7 cells. Apoptosis induced by SRJ09 and SRJ23 in HCT-116
      cells was confirmed by annexin V-FITC/PI flow cytometry analysis. CONCLUSION AND
      IMPLICATIONS: The new benzylidene derivatives of andrographolide are potential
      anticancer agents. SRJ09 emerged as the lead compound in this study, exhibiting
      anticancer activity by downregulating CDK4 to promote a G(1) phase cell cycle
      arrest, coupled with induction of apoptosis.

PMID- 18806813
TI  - Identification of alpha 1L-adrenoceptor in mice and its abolition by alpha 1A
      adrenoceptor gene knockout.
AB  - BACKGROUND AND PURPOSE: The alpha(1L)-adrenoceptor has pharmacological properties
      that distinguish it from three classical alpha(1)-adrenoceptors (alpha(1A),
      alpha(1B) and alpha(1D)). The purpose of this was to identify alpha(1L)
      adrenoceptors in mice and to examine their relationship to classical alpha(1)
      adrenoceptors. EXPERIMENTAL APPROACH: Radioligand binding and functional bioassay
      experiments were performed on the cerebral cortex, vas deferens and prostate of
      wild-type (WT) and alpha(1A)-, alpha(1B)- and alpha(1D)-adrenoceptor gene
      knockout (AKO, BKO and DKO) mice. KEY RESULTS: The radioligand [(3)H]-silodosin
      bound to intact segments of the cerebral cortex, vas deferens and prostate of WT,
      BKO and DKO but not of AKO mice. The binding sites were composed of two
      components with high and low affinities for prazosin or RS-17053, indicating the
      pharmacological profiles of alpha(1A)-adrenoceptors and alpha(1L)-adrenoceptors.
      In membrane preparations of WT mouse cortex, however, [(3)H]-silodosin bound to a
      single population of prazosin high-affinity sites, suggesting the presence of
      alpha(1A)-adrenoceptors alone. In contrast, [(3)H]-prazosin bound to two
      components having alpha(1A)-adrenoceptor and alpha(1B)-adrenoceptor profiles in
      intact segments of WT and DKO mouse cortices, but AKO mice lacked alpha(1A)
      adrenoceptor profiles and BKO mice lacked alpha(1B)-adrenoceptor profiles.
      Noradrenaline produced contractions through alpha(1L)-adrenoceptors with low
      affinity for prazosin in the vas deferens and prostate of WT, BKO and DKO mice.
      However, the contractions were abolished or markedly attenuated in AKO mice.
      CONCLUSIONS AND IMPLICATIONS: alpha(1L)-Adrenoceptors were identified as binding
      and functional entities in WT, BKO and DKO mice but not in AKO mice, suggesting
      that the alpha(1L)-adrenoceptor is one phenotype derived from the alpha(1A)
      adrenoceptor gene.

PMID- 18806814
TI  - The guinea-pig tracheal potential difference as an in vivo model for the study of
      epithelial sodium channel function in the airways.
AB  - BACKGROUND AND PURPOSE: The epithelial sodium channel (ENaC) is a key regulator
      of airway mucosal hydration and mucus clearance. Negative regulation of airway
      ENaC function is predicted to be of clinical benefit in the cystic fibrosis lung.
      The aim of this study was to develop a small animal model to enable the direct
      assessment of airway ENaC function in vivo. EXPERIMENTAL APPROACH: Tracheal
      potential difference (TPD) was utilized as a measure of airway epithelial ion
      transport in the guinea-pig. ENaC activity in the trachea was established with a
      dose-response assessment to a panel of well-characterized direct and indirect
      pharmacological modulators of ENaC function, delivered by intra-tracheal (i.t.)
      instillation. KEY RESULTS: The TPD in anaesthetized guinea-pigs was attenuated by
      the direct ENaC blockers: amiloride, benzamil and CF552 with ED(50) values of 16,
      14 and 0.2 microg kg(-1) (i.t.), respectively. 5-(N-Ethyl-N-isopropyl) amiloride,
      a structurally related compound but devoid of activity on ENaC, was without
      effect on the TPD. Intra-tracheal dosing of the Kunitz-type serine protease
      inhibitors aprotinin and placental bikunin, which have previously been
      demonstrated to inhibit proteolytic activation of ENaC, likewise potently
      attenuated TPD in guinea-pigs, whereas alpha(1)-antitrypsin and soya bean trypsin
      inhibitor were without effect. CONCLUSIONS AND IMPLICATIONS: The pharmacological
      sensitivity of the TPD to amiloride analogues and also to serine protease
      inhibitors are both consistent with that of ENaC activity in the guinea-pig
      trachea. The guinea-pig TPD therefore represents a suitable in vivo model of
      human airway epithelial ion transport.

PMID- 18806815
TI  - Virodhamine relaxes the human pulmonary artery through the endothelial
      cannabinoid receptor and indirectly through a COX product.
AB  - BACKGROUND AND PURPOSE: The endocannabinoid virodhamine is a partial agonist at
      the cannabinoid CB(1) receptor and a full agonist at the CB(2) receptor, and
      relaxes rat mesenteric arteries through endothelial cannabinoid receptors. Its
      concentration in the periphery exceeds that of the endocannabinoid anandamide.
      Here, we examined the influence of virodhamine on the human pulmonary artery.
      EXPERIMENTAL APPROACH: Isolated human pulmonary arteries were obtained during
      resections for lung carcinoma. Vasorelaxant effects of virodhamine were examined
      on endothelium-intact vessels precontracted with 5-HT or KCl. KEY RESULTS:
      Virodhamine, unlike WIN 55,212-2, relaxed 5-HT-precontracted vessels
      concentration dependently. The effect of virodhamine was reduced by endothelium
      denudation, two antagonists of the endothelial cannabinoid receptor, cannabidiol
      and O-1918, and a high concentration of the CB(1) receptor antagonist rimonabant
      (5 muM), but only slightly attenuated by the NOS inhibitor L-NAME and not
      affected by a lower concentration of rimonabant (100 nM) or by the CB(2) and
      vanilloid receptor antagonists SR 144528 and capsazepine, respectively. The COX
      inhibitor indomethacin and the fatty acid amide hydrolase inhibitor URB597 and
      combined administration of selective blockers of small (apamin) and intermediate
      and large (charybdotoxin) conductance Ca(2+)-activated K(+) channels attenuated
      virodhamine-induced relaxation. The vasorelaxant potency of virodhamine was lower
      in KCl- than in 5-HT-precontracted preparations. CONCLUSIONS AND IMPLICATIONS:
      Virodhamine relaxes the human pulmonary artery through the putative endothelial
      cannabinoid receptor and indirectly through a COX-derived vasorelaxant prostanoid
      formed from the virodhamine metabolite, arachidonic acid. One or both of these
      mechanisms may stimulate vasorelaxant Ca(2+)-activated K(+) channels.

PMID- 18806816
TI  - Use of atorvastatin as an anti-inflammatory treatment in Crohn's disease.
AB  - BACKGROUND AND PURPOSE: Experimental and clinical investigations have revealed
      that statins can downregulate both acute and chronic inflammatory processes.
      Whether statins express anti-inflammatory activities in the treatment of Crohn's
      disease is unknown. EXPERIMENTAL APPROACH: Ten patients were given 80 mg
      atorvastatin once daily for 13 weeks and then followed up for 8 weeks after the
      treatment. The anti-inflammatory effects of statin were assessed by measuring
      levels of plasma C-reactive protein (CRP), soluble (s) CD14, tumour necrosis
      factor (TNF)-alpha, sTNFRI and II, CCL2 and 8 and the mucosal inflammation by
      faecal calprotectin. Circulating monocytes were subgrouped and their chemokine
      receptor expression of CCR2 and CX(3)CR1 were analysed. KEY RESULTS: In 8 of 10
      patients, atorvastatin treatment reduced CRP (P=0.008) and sTNFRII (P=0.064). A
      slight decrease in plasma levels of sCD14, TNF-alpha and sTNFRI was observed in
      7/10 patients and faecal calprotectin was reduced in 8/10 patients. We also
      observed that the treatment diminished expression of CCR2 and CX(3)CR1 on
      monocyte populations (P=0.014). At the follow-up visit, 8 weeks after the
      atorvastatin treatment was terminated, CRP levels had returned to those seen
      before the treatment. CONCLUSIONS AND IMPLICATIONS: Our findings imply that
      atorvastatin therapy reduces inflammation in patients with Crohn's disease and,
      therefore, encourage further investigations of statin-mediated protective effects
      in inflammatory bowel diseases.

PMID- 18806817
TI  - Differential role of tachykinin NK3 receptors on cholinergic excitatory
      neurotransmission in the mouse stomach and small intestine.
AB  - BACKGROUND AND PURPOSE: Tachykinin NK(3) receptors are widely expressed in the
      mouse gastrointestinal tract but their functional role in enteric neuromuscular
      transmission remains unstudied in this species. We investigated the involvement
      of NK(3) receptors in cholinergic neurotransmission in the mouse stomach and
      small intestine. EXPERIMENTAL APPROACH: Muscle strips of the mouse gastric fundus
      and ileum were mounted in organ baths for tension recordings. Effects of NK(3)
      agonists and antagonists were studied on contractions to EFS of enteric nerves
      and to carbachol. KEY RESULTS: EFS induced frequency-dependent tetrodotoxin
      sensitive contractions, which were abolished by atropine. The cholinergic
      contractions to EFS in the stomach were enhanced by the NK(3) antagonist
      SR142801, but not affected by the NK(3) agonist senktide or neurokinin B. The
      cholinergic contractions to EFS in the small intestine were not affected by
      SR142801, but dose-dependently inhibited by senktide and neurokinin B. This
      inhibitory effect was prevented by SR142801 but not by hexamethonium. SR142801,
      senktide or neurokinin B did not induce any response per se in the stomach and
      small intestine and did not affect contractions to carbachol. CONCLUSIONS AND
      IMPLICATIONS: NK(3) receptors modulate cholinergic neurotransmission differently
      in the mouse stomach and small intestine. Blockade of NK(3) receptors enhanced
      cholinergic transmission in the stomach but not in the intestine. Activation of
      NK(3) receptors inhibited cholinergic transmission in the small intestine but not
      in the stomach. This indicates a physiological role for NK(3) receptors in mouse
      stomach contractility and a pathophysiological role in mouse intestinal
      contractility.

PMID- 18806818
TI  - Peroxynitrite: in vivo cardioprotectant or arrhythmogen?
AB  - The factors that determine susceptibility to lethal ventricular arrhythmias
      during myocardial ischaemia and reperfusion in vivo are complex, but the balance
      between proarrhythmic and antiarrhythmic endogenous substances is likely to be
      important. However, in this context, it is not well established what effect
      endogenously produced peroxynitrite has on arrhythmias that develop during
      ischaemia/reperfusion in vivo. The study by Kiss et al., published in this issue
      of the BJP, provides some insights to this problem. We discuss the wider
      implications of this study as well as issues that still require resolution.

PMID- 18806819
TI  - Intra- and extrarenal arteries exhibit different profiles of contractile
      responses in high glucose conditions.
AB  - BACKGROUND AND PURPOSE: The renal artery (RA) has been extensively investigated
      for the assessment of renal vascular function/dysfunction; however, few studies
      have focused on the intrarenal vasculature. EXPERIMENTAL APPROACH: We devised a
      microvascular force measurement system, which allowed us to measure contractions
      of interlobar arteries (ILA), isolated from within the mouse kidney and prepared
      without endothelium. KEY RESULTS: KCl (50 mM) induced similar force development
      in the aorta and RA but responses in the ILA were about 50% lower. Treatment of
      RA with 10 microM phenylephrine (PE), 10 nM U46619 (thromboxane A(2) analogue) or
      10 microM prostaglandin F(2 alpha) elicited a response greater than 150% of that
      induced by KCl. In ILA, 10 nM U46619 elicited a response that was 130% of the KCl
      induced response; however, other agonists induced levels similar to that induced
      by KCl. High glucose conditions (22.2 mM glucose) significantly enhanced
      responses in RA and ILA to PE or U46619 stimulation. This enhancement was
      suppressed by rottlerin, a calcium-independent PKC inhibitor, indicating that
      glucose-dependent, enhanced small vessel contractility in the kidney was linked
      to the activation of calcium-independent PKC. CONCLUSION AND IMPLICATIONS: Extra-
      and intrarenal arteries exhibit different profiles of agonist-induced
      contractions. In ILA, only U46619 enhanced small vessel contractility in the
      kidney, which might lead to renal dysfunction and nephropathy through reduced
      intrarenal blood flow rate. A model has been established, which will allow the
      assessment of contractile responses of intrarenal arteries from murine models of
      renal disease, including type 2 diabetes.

PMID- 18806820
TI  - Potential importance of alterations in hydrogen sulphide (H2S) bioavailability in
      diabetes.
AB  - Despite its long-standing reputation as a foul smelling and toxic gas that is
      associated with the decay of biological matter,hydrogen sulphide (H2S) has
      emerged as an important regulator of cardiovascular homoeostasis. H2S promotes a
      number of cellular signals that regulate metabolism, cardiac function and cell
      survival. Endogenous H2S bioavailability is regulated by several enzymes involved
      in the biosynthesis of cysteine. This study by Brancaleone et al. in the current
      issue of the British Journal of Pharmacology provides novel insights into the
      impairment of H2S biosynthesis in the setting of diabetes mellitus. The authors
      report that enzymic H2S biosynthesis is impaired in a murine model of type 1
      diabetes and the attenuation in H2S bioavailability is associated with impaired
      vascular reactivity. This study has profound implications for the use of
      pharmacological agents to augment endogenous H2S synthesis or agents that release
      H2S to augment the levels of this gaseous signalling molecule in cardiovascular
      disease.

PMID- 18806821
TI  - An endogenous regulator of inflammation, resolvin E1, modulates osteoclast
      differentiation and bone resorption.
AB  - BACKGROUND AND PURPOSE: The inflammation-resolving lipid mediator resolvin E1
      (RvE1) effectively stops inflammation-induced bone loss in vivo in experimental
      periodontitis. It was of interest to determine whether RvE1 has direct actions on
      osteoclast (OC) development and bone resorption. EXPERIMENTAL APPROACH: Primary
      OC cultures derived from mouse bone marrow were treated with RvE1 and analysed
      for OC differentiation, cell survival and bone substrate resorption. Receptor
      binding was measured using radiolabelled RvE1. Nuclear factor (NF)-kappaB
      activation and Akt phosphorylation were determined with western blotting. Lipid
      mediator production was assessed with liquid chromatography tandem mass
      spectrometry. KEY RESULTS: OC growth and resorption pit formation were markedly
      decreased in the presence of RvE1. OC differentiation was inhibited by RvE1 as
      demonstrated by decreased number of multinuclear OC, a delay in the time course
      of OC development and attenuation of receptor activator of NF-kappaB ligand
      induced nuclear translocation of the p50 subunit of NF-kappaB. OC survival and
      apoptosis were not altered by RvE1. Messenger RNA for both receptors of RvE1,
      ChemR23 and BLT(1) is expressed in OC cultures. Leukotriene B(4) (LTB(4))
      competed with [(3)H]RvE1 binding on OC cell membrane preparations, and the LTB(4)
      antagonist U75302 prevented RvE1 inhibition of OC growth, indicating that BLT(1)
      mediates RvE1 actions on OC. Primary OC synthesized the RvE1 precursor 18R
      hydroxy-eicosapentaenoic acid and LTB(4). Co-incubation of OC with peripheral
      blood neutrophils resulted in transcellular RvE1 biosynthesis. CONCLUSIONS AND
      IMPLICATIONS: These results indicate that RvE1 inhibits OC growth and bone
      resorption by interfering with OC differentiation. The bone-sparing actions of
      RvE1 are in addition to inflammation resolution, a direct action in bone
      remodelling.

PMID- 18806822
TI  - Desensitization of the soluble guanylyl cyclase/cGMP pathway by
      lipopolysaccharide in rat isolated pulmonary artery but not aorta.
AB  - BACKGROUND AND PURPOSE: To investigate the function of soluble guanylyl cyclase
      (sGC)/3',5'-cyclic guanosine monophosphate (cGMP) pathway in lipopolysaccharide
      (LPS)-induced changes in vascular reactivity of rat isolated pulmonary artery and
      aorta. EXPERIMENTAL APPROACH: Nitric oxide (NO) production, contraction responses
      to endothelin-1 (ET-1), relaxation responses to sodium nitroprusside (SNP), 8
      pCPT-cGMP, BAY412272 and T-0156, SNP-induced cGMP production and expression of
      sGC(alpha1), sGC(beta1) and 3',5'-cyclic nucleotide phosphodiesterase-5 (PDE5)
      proteins were measured in LPS-treated pulmonary and aortic rings from male Wistar
      rats. KEY RESULTS: In both vessels, LPS (10 microg mL(-1), 20 h) increased NO
      production, which was inhibited by the selective inducible NOS (iNOS) inhibitor
      1400W (1 microM). In the aorta, LPS decreased ET-1-induced contractility and this
      decrease was inhibited by the selective sGC inhibitor ODQ (10 microM) but not by
      removal of endothelium, or inhibitors of cyclooxygenase (indomethacin, 10 microM)
      or iNOS (1400W, 1 microM). Furthermore, aortic relaxation responses to the direct
      sGC activator BAY412272 were enhanced. In the pulmonary artery, SNP (1 nM to 30
      microM)-induced relaxation and cGMP production, BAY412272-induced relaxation and
      sGC(beta1) protein expression were decreased, whereas relaxation responses to the
      PDE5-specific inhibitor T-0156 (0.1-100 nM) were enhanced. Relaxation responses
      to the phosphodiesterase-resistant cGMP analogue, 8-pCPT-cGMP, and protein
      expression levels of sGC(alpha1) and PDE5 were not altered in either vessel.
      CONCLUSION AND IMPLICATIONS: LPS caused a selective hypocontractility of rat
      aorta to ET-1 mediated mainly through NO-independent sGC activation, whereas in
      the pulmonary artery, the effect of sGC activation was reduced by a decreased
      protein expression of sGC(beta1) together with increased PDE5 activity.

PMID- 18806823
TI  - CSR1 induces cell death through inactivation of CPSF3.
AB  - CSR1 (cellular stress response 1), a newly characterized tumor-suppressor gene,
      undergoes hypermethylation in over 30% of prostate cancers. Re-expression of CSR1
      inhibits cell growth and induces cell death, but the mechanism by which CSR1
      suppresses tumor growth is not clear. In this study, we screened a prostate cDNA
      library using a yeast two-hybrid system and found that the cleavage and
      polyadenylation-specific factor 3 (CPSF3), an essential component for converting
      heteronuclear RNA to mRNA, binds with high affinity to the CSR1 C terminus.
      Further analyses determined that the binding motifs for CPSF3 are located between
      amino acids 440 and 543. The interaction between CSR1 and CPSF3 induced CPSF3
      translocation from the nucleus to the cytoplasm, resulting in inhibition of
      polyadenylation both in vitro and in vivo. Downregulation of CPSF3 using small
      interfering RNA induced cell death in a manner similar to CSR1 expression. A CSR1
      mutant unable to bind to CPSF3 did not alter CPSF3 subcellular distribution, did
      not inhibit its polyadenylation activity and did not induce cell death. In
      summary, CSR1 appears to induce cell death through a novel mechanism by hijacking
      a critical RNA processing enzyme.

PMID- 18806824
TI  - Oncogene activation in melanocytes links reactive oxygen to multinucleated
      phenotype and senescence.
AB  - Contrary to malignant melanoma, nevi are a benign form of melanocytic
      hyperproliferation. They are frequently observed as precursor lesions of
      melanoma, but they also feature biochemical markers of senescence. In particular,
      evidence for oncogene-induced melanocyte senescence as natural means to prevent
      tumorigenesis has been obtained in nevi with mutated B-Raf(V600E). Here, we
      demonstrate that strong oncogenic growth factor receptor signalling drives
      melanocytes into senescence, whereas weaker signals keep them in the
      proliferative state. Activation of oncogene-induced senescence also produces
      multinucleated giant cells, a long known histological feature of nevus cells. The
      protein levels of the senescence mediators, p53 and pRB, and their upstream
      activators do not correlate with senescence. However, strong oncogene signalling
      leads to pronounced reactive oxygen stress, and scavenging of reactive oxygen
      species (ROS) efficiently prevents the formation of multinucleated cells and
      senescence. Similarly, expression of oncogenic N-RAS results in ROS generation,
      DNA damage and the same multinuclear senescent phenotype. Hence, we identified
      oncogenic signalling-dependent ROS production as critical mediator of the
      melanocytic multinuclear phenotype and senescence, both of them being hallmarks
      of human nevus cells.

PMID- 18806825
TI  - A role for candidate tumor-suppressor gene TCEAL7 in the regulation of c-Myc
      activity, cyclin D1 levels and cellular transformation.
AB  - The pathophysiological mechanisms that drive the development and progression of
      epithelial ovarian cancer remain obscure. Recently, we identified TCEAL7 as a
      transcriptional regulatory protein often downregulated in epithelial ovarian
      cancer. However, the biological significance of such downregulation in cancer is
      not currently known. Here, we show that TCEAL7 is downregulated frequently in
      many human cancers and that in immortalized human ovarian epithelial cells this
      event promotes anchorage-independent cell growth. Mechanistic investigations
      revealed that TCEAL7 associates with cyclin D1 promoter containing Myc E-box
      sequence and transcriptionally represses cyclin D1 expression. Moreover,
      downregulation of TCEAL7 promotes DNA-binding activity of Myc-Max, and
      upregulates the promoter activity of c-Myc-target gene, ornithine decarboxylase
      (ODC), whereas enhanced expression of TCEAL7 inhibits Myc-induced promoter
      activity of ODC. Our findings suggest that TCEAL7 may restrict ovarian epithelial
      cell transformation by limiting Myc activity. These results also suggest a
      potential, alternative mechanism by which c-Myc activity may be deregulated in
      cancer by the downregulation of TCEAL7.

PMID- 18806826
TI  - Repression of E-cadherin by the polycomb group protein EZH2 in cancer.
AB  - Enhancer of zeste homolog 2 (EZH2) is a critical component of the polycomb
      repressive complex 2 (PRC2), which is involved in gene silencing and histone H3
      lysine 27 methylation. EZH2 has a master regulatory function in controlling such
      processes as stem cell differentiation, cell proliferation, early embryogenesis
      and X chromosome inactivation. Although benign epithelial cells express very low
      levels of EZH2, increased levels of EZH2 have been observed in aggressive solid
      tumors such as those of the prostate, breast and bladder. The mechanism by which
      EZH2 mediates tumor aggressiveness is unclear. Here, we demonstrate that EZH2
      mediates transcriptional silencing of the tumor suppressor gene E-cadherin by
      trimethylation of H3 lysine 27. Histone deacetylase inhibitors can prevent EZH2
      mediated repression of E-cadherin and attenuate cell invasion, suggesting a
      possible mechanism that may be useful for the development of therapeutic
      treatments. Taken together, these observations provide a novel mechanism of E
      cadherin regulation and establish a functional link between dysregulation of EZH2
      and repression of E-cadherin during cancer progression.

PMID- 18806827
TI  - Cooperative effect of p21Cip1/WAF-1 and 14-3-3sigma on cell cycle arrest and
      apoptosis induction by p14ARF.
AB  - P14(ARF) (p19(ARF) in the mouse) plays a central role in the regulation of
      cellular proliferation. Although the capacity of p14(ARF) to induce a cell cycle
      arrest in G1 phase depends on a functional p53/p21-signaling axis, the G2 arrest
      triggered by p14(ARF) is p53/p21-independent. Using isogeneic HCT116 cells either
      wild-type or homozygously deleted for p21, 14-3-3sigma or both, we further
      investigated the cooperative effect of p21 and 14-3-3sigma on cell cycle
      regulation and apoptosis induction by p14(ARF). In contrast to DNA damage, which
      induces mitotic catastrophe in 14-3-3sigma-deficient cells, we show here that the
      expression of p14(ARF) triggers apoptotic cell death, as evidenced by nuclear DNA
      fragmentation and induction of pan-caspase activities, irrespective of the
      presence or absence of 14-3-3sigma. The activation of the intrinsic mitochondrial
      apoptosis pathway by p14(ARF) was confirmed by cytochrome c release from
      mitochondria and induction of caspase-9- (LEHDase) and caspase-3/7-like (DEVDase)
      activities. Moreover, 14-3-3sigma/p21 double-deficient cells were exceedingly
      sensitive to apoptosis induction by p14(ARF) as compared to wild-type cells or
      cells lacking either gene alone. Notably, p14(ARF)-induced apoptosis was preceded
      by an arrest in the G2 phase of cell cycle, which coincided with downregulation
      of cdc2 (cdk1) protein expression and lack of its nuclear localization. This
      indicates that p14(ARF) impairs mitotic entry by targeting the distal DNA damage
      signaling pathway and induces apoptotic cell death, rather than mitotic
      catastrophe, out of a transient G2 arrest. Furthermore, our data delineate that
      the disruption of G2/M cell cycle checkpoint control critically determines the
      sensitivity of the cell toward p14(ARF)-induced mitochondrial apoptosis.

PMID- 18806828
TI  - Therapeutic targeting of Id2 reduces growth of human colorectal carcinoma in the
      murine liver.
AB  - During development inhibitor of DNA-bind-2 (Id2) regulates proliferation and
      differentiation. Id2 expression has been detected in cancer cells, yet its
      cellular function and validity as a therapeutic target remains largely unknown.
      Immunohistochemical analysis of colorectal cancer (CRC) specimens revealed that
      Id2 was undetectable in normal colonic mucosa, but occurs in 40% of primary
      tumors and in most CRC liver metastases (P<0.0001). Additionally, Id2 was
      expressed in all CRC cell lines assayed. CRC cells with reduced Id2 expression
      demonstrated reduced proliferation. Analysis of CRC cell cycle regulatory
      proteins showed that reducing Id2 levels reduces cyclin D1 levels and increased
      p21 levels. Reduction of Id2 expression also enhanced tumor cell apoptosis,
      increasing levels of the pro-apoptotic protein Bim/Bod, and cleavage of caspase-7
      and poly (ADP-ribose) polymerase. In vivo studies show tumors derived from cells
      with decreased Id2 levels formed smaller tumors with fewer metastases compared
      with tumors with normal levels (P<0.05). Furthermore, intraperitoneal
      administration of Id2 small interfering RNA (siRNA) conjugated with the neutral
      liposome 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine decreased tumor burden in
      mice compared with control treatment (P=0.006). We conclude that Id2 is
      upregulated in CRC, and is important in promoting cell survival. In vivo
      targeting of Id2 by siRNA establishes that it is a valid therapeutic target where
      its expression occurs.

PMID- 18806829
TI  - beta-catenin mediates glandular formation and dysregulation of beta-catenin
      induces hyperplasia formation in the murine uterus.
AB  - Endometrioid adenocarcinoma is the most frequent form of endometrial cancer,
      usually developing in pre- and peri-menopausal women. beta-catenin abnormalities
      are common in endometrioid type endometrial carcinomas with squamous
      differentiation. To investigate the role of beta-catenin (Ctnnb1) in uterine
      development and tumorigenesis, mice were generated which expressed a dominant
      stabilized beta-catenin or had beta-catenin conditionally ablated in the uterus
      by crossing the PR(Cre) mouse with the Ctnnb1(f(ex3)/+) mouse or Ctnnb1(f/f)
      mouse, respectively. Both of the beta-catenin mutant mice have fertility defects
      and the ability of the uterus to undergo a hormonally induced decidual reaction
      was lost. Expression of the dominant stabilized beta-catenin,
      PR(cre/+)Ctnnb1(f(ex3)/+), resulted in endometrial glandular hyperplasia, whereas
      ablation of beta-catenin, PR(cre/+)Ctnnb1(f/f), induced squamous cell metaplasia
      in the murine uterus. Therefore, we have demonstrated that correct regulation of
      beta-catenin is important for uterine function as well as in the regulation of
      endometrial epithelial differentiation.

PMID- 18806830
TI  - Colorectal cancer cells with the BRAF(V600E) mutation are addicted to the ERK1/2
      pathway for growth factor-independent survival and repression of BIM.
AB  - The RAF-mitogen-activated protein kinase kinase 1/2-extracellular signal
      regulated kinase 1/2 (RAF-MEK1/2-ERK1/2) pathway is activated in many human
      tumours and can protect cells against growth factor deprivation; however, most
      such studies have relied upon overexpression of RAF or MEK constructs that are
      not found in tumours. Here we show that expression of the endogenous BRAF(V600E)
      allele in mouse embryonic fibroblasts from conditional knock-in transgenic mice
      activates ERK1/2, represses the BH3-only protein BIM and protects cells from
      growth factor withdrawal. Human colorectal cancer (CRC) cell lines harbouring
      BRAF(V600E) are growth factor independent for the activation of ERK1/2 and
      survival. However, treatment with the MEK1/2 inhibitors U0126, PD184352 or the
      novel clinical candidate AZD6244 (ARRY-142886) overcomes growth factor
      independence, causing CRC cell death. BIM is de-phosphorylated and upregulated
      following MEK1/2 inhibition in all CRC cell lines studied and knockdown of BIM
      reduces cell death, indicating that repression of BIM is a major part of the
      ability of BRAF(V600E) to confer growth factor-independent survival. We conclude
      that a single endogenous BRAF(V600E) allele is sufficient to repress BIM and
      prevent death arising from growth factor withdrawal, and CRC cells with
      BRAF(V600E) mutations are addicted to the ERK1/2 pathway for repression of BIM
      and growth factor-independent survival.

PMID- 18806831
TI  - Promotion of glioma cell survival by acyl-CoA synthetase 5 under extracellular
      acidosis conditions.
AB  - Extracellular acidosis (low pH) is a tumor microenvironmental stressor that has a
      critical function in the malignant progression and metastatic dissemination of
      tumors. To survive under stress conditions, tumor cells must evolve resistance to
      stress-induced toxicity. Acyl-CoA synthetase 5 (ACSL5) is a member of the ACS
      family, which converts fatty acid to acyl-CoA. ACSL5 is frequently overexpressed
      in malignant glioma, whereas its functional significance is still unknown. Using
      retrovirus-mediated stable gene transfer (gain of function) and small interfering
      RNA-mediated gene silencing (loss of function), we show here that ACSL5
      selectively promotes human glioma cell survival under extracellular acidosis.
      ACSL5 enhanced cell survival through its ACS catalytic activity. To clarify the
      genome-wide changes in cell signaling pathways by ACSL5, we performed cDNA
      microarray analysis and identified an ACSL5-dependent gene expression signature.
      The analysis revealed that ACSL5 was critical to the expression of tumor-related
      factors including midkine (MDK), a heparin-binding growth factor frequently
      overexpressed in cancer. Knockdown of MDK expression significantly attenuated
      ACSL5-mediated survival under acidic state. These results indicate that ACSL5 is
      a critical factor for survival of glioma cells under acidic tumor
      microenvironment, thus providing novel molecular basis for cancer therapy.

PMID- 18806832
TI  - Expression and functional analysis of G1 to S regulatory components reveals an
      important role for CDK2 in cell cycle regulation in human embryonic stem cells.
AB  - One of the characteristic features of human embryonic stem cells (hESCs) is the
      competence for self-renewal and pluripotency. To date, little is known about cell
      cycle regulation in these cells and how the cell cycle machinery influences hESCs
      properties. A common feature of human, murine and primate ESCs is the presence of
      a short G1 phase, which has been viewed as a time window during which stem cells
      are exposed to differentiation signals. We used the hESCs differentiation model
      and comparisons to human embryonic carcinoma (EC) cells to study the key
      regulators of G1 to S transition in hESCs. Our studies show that hESCs express
      all G1-specific CYCLINs (D1, D2, D3 and E) and cyclin-dependent kinases (CDK)
      (CDK2, CDK4 and CDK6) at variable levels. In contrast to murine ESCs, most of the
      cell cycle regulators in hESCs show cell cycle-dependent expression, thus
      revealing important differences in the expression of cell cycle regulatory
      components between these two embryonic cell types. Knockdown of CDK2 using RNA
      interference resulted in hESCs arrest at G1 phase of the cell cycle and
      differentiation to extraembryonic lineages. This suggests an important role for
      CDK2 in cell cycle regulation in hESCs that are likely to bear significant
      impacts on the maintenance of their pluripotent phenotype.

PMID- 18806833
TI  - EPO in combination with G-CSF improves mobilization effectiveness after
      chemotherapy with ifosfamide, epirubicin and etoposide and reduces costs during
      mobilization and transplantation of autologous hematopoietic progenitor cells.
AB  - A successful stem cell harvest is a prerequisite for peripheral blood SCT. We
      investigated the number of CD34(+) cells mobilized, the number of leukaphereses
      needed and the expenses of treatment for 28 patients with multiple myeloma
      randomly assigned to receive either G-CSF alone or G-CSF+EPO for stem cell
      mobilization after chemotherapy with ifosfamide, epirubicin and etoposide. All
      patients treated with G-CSF+EPO reached the threshold of 6 x 10(6) CD34(+) cells
      per kg body weight (kgbw), with a mean of 1.3 leukaphereses. On average 15.4 x
      10(6) CD34(+) cells/kgbw were collected. In the G-CSF-alone group, the mean
      number of leukaphereses was 1.8, and 12.6 x 10(6) CD34(+) cells/kgbw were
      collected, and two patients failed the threshold. Overall costs per patient for
      mobilization and leukaphereses were 8339 euro (G-CSF+EPO) and 8842 euro (G-CSF).
      After transplantation, fewer blood transfusions (0.6 versus 1.3, P=0.05), fewer
      days on antibiotics (2.3 versus 6.1, P=0.02) and a shorter hospital stay (15.2
      versus 17.8, P=0.06) were noted in the G-CSF+EPO group resulting in a 19.2%
      reduction of costs for each transplant (P=0.018). In summary, EPO improves the
      mobilization efficiency of G-CSF and so reduces costs of mobilization and SCT.

PMID- 18806834
TI  - Focal nodular hyperplasia of the liver following hematopoietic SCT.
AB  - Incidental hepatic regenerating nodules rarely occur after haematopoietic SCT
      (HSCT). Focal nodular hyperplasia (FNH) is one of these unusual benign tumors
      with characteristic imaging features. To determine the incidence and the outcome
      of FNH of the liver and improve the understanding of its pathogenesis, we
      prospectively surveyed a total of 138 patients who had undergone serial
      prospective pre- and post-transplantation evaluations of iron biomarkers,
      including ferritin and liver iron concentration assessed by magnetic resonance
      imaging (MRI). Seventeen patients with a median delay of 6.4 years (2.2-13.6)
      developed FNH of the liver. All were children at the time of transplantation. MR
      images were typical for FNH in 16 patients; only one patient needed a
      confirmatory biopsy. Sixteen had received a myeloablative conditioning; six
      received a BU-based preparation and 10 TBI. Three patients experienced sinusoidal
      obstruction syndrome. Neither complication nor malignant transformation has been
      reported to date. FNH of the liver seems to be a frequent delayed benign
      complication following HSCT, probably of iatrogenic vascular origin. Basic
      clinical and diagnostic imaging follow-up is warranted.

PMID- 18806835
TI  - Little impact of donor/recipient major mismatch for neutrophil-specific antigen
      NA2 on neutrophil recovery after allogeneic SCT.
AB  - The Fcgamma receptor IIIb (FcgammaRIIIb), a receptor for the Fcgamma region of
      IgG, is specifically expressed on neutrophils. It has two allelic polymorphisms,
      NA1 and NA2, which are highly immunogenic and act as targets in alloimmune or
      autoimmune neutropenia. Thus, neutrophil antigens (NA) compatibility of
      donor/recipient pairs might be expected to affect the engraftment of neutrophils
      after allogeneic SCT (allo-SCT). Here, the impact of NA compatibility of 17
      patients and their donors undergoing allo-SCT with a myeloablative regimen was
      determined. Leukocyte depletion filters were used for all transfusions before and
      post-SCT; most patients received G-CSF after transplant. Major mismatches for NA1
      and NA2 were present in 1 and 7 patient/donor pairs, respectively. These eight
      patients receiving NA major-mismatched allo-SCT were compared with nine patients
      who received NA compatible allo-SCT. Engraftment of neutrophils and the incidence
      of post-engraftment neutropenia were found to be identical in the two groups.
      Despite the limitations in statistical power because of the small number of
      patients analyzed, these observations suggest that the major mismatching for NA2
      antigen has little impact on the engraftment of neutrophils after myeloablative
      allo-SCT, at least in patients transfused using leukocyte depletion filters and
      receiving G-CSF after transplantation.

PMID- 18806836
TI  - Selective apoptosis of monocytes and monocyte-derived DCs induced by bortezomib
      (Velcade).
AB  - Bortezomib, a proteasome inhibitor, has shown immunosuppressive activity in
      animal models of GVHD. In this study, we evaluated the effects of Bortezomib on
      the survival of monocytes, a major circulating source of DCs. PBMCs or purified
      CD14+ monocytes were cultured for 24 h with Bortezomib (0.1-100 ng/ml). Apoptosis
      was demonstrated on the basis of detection of phosphatydilserine. Bortezomib
      induced a significant dose-dependent depletion (P=0.008) of monocytes in PBMC
      preparations, with <1% CD14+ cells remaining at doses >or=5 ng/ml. Moreover,
      Bortezomib decreased the survival of purified monocytes within 24 h (P=0.004)
      (n=6). Monocyte loss was due to apoptosis (effective dose 50%, ED(50), 1-10
      ng/ml). In addition, both immature and mature monocyte-derived DC underwent
      apoptosis following exposure to Bortezomib. Kinetic experiments showed that
      apoptosis increased at 16 h through 24 h of culture. However, short term (4 h)
      incubation with Bortezomib irreversibly committed monocytes to undergo apoptosis
      at 24, 72 and 144 h. Instead, Bortezomib induced no apoptosis of purified CD19+
      B, CD3+ T lymphocytes and CD34+ progenitor cells (ED(50) >50 ng/ml). The
      inhibitory effect of Bortezomib on professional APCs, such as monocytes and DCs,
      suggests its possible use in GVHD prophylaxis.

PMID- 18806837
TI  - Outcome following unrelated cord blood transplant in 136 patients with malignant
      and non-malignant diseases: a report from the Australian and New Zealand
      children's haematology and oncology group.
AB  - Unrelated umbilical cord blood (UCB) is an alternative stem cell source for
      paediatric patients lacking a matched related or unrelated marrow donor. We
      report the results of all paediatric unrelated UCB transplants performed in
      Australia and New Zealand over a 10-year period. A total of 135 patients were
      transplanted, 100 for malignant disease (74%) and 35 for non-malignant disorders.
      The majority (88%) of patients received an HLA-mismatched graft. The median
      infused total nucleated cell dose was 4.7 x 10(7)/kg and CD34+ count 1.9 x
      10(5)/kg. Neutrophil engraftment occurred in 83% of patients by day 42 (median 23
      days) and platelet engraftment in 55% by day 60 (median 56 days). Grades II-IV
      and III-IV acute GVHD occurred in 41 and 18% of patients, respectively. TRM and
      overall survival 1-year post transplant were 32 and 61%, respectively. A higher
      probability of neutrophil recovery (P=0.004) and faster time to recovery (median
      18 days vs 26 days, P=0.008) were observed in recipients of a cord unit with a
      CD34 cell dose >or=1.7 x 10(5)/kg. Our results support selection of cord units
      with CD34 cell doses >or=1.7 x 10(5)/kg to promote faster engraftment, improve
      survival and lower TRM.

PMID- 18806838
TI  - Fewer infections and lower infection-related mortality following non
      myeloablative versus myeloablative conditioning for allotransplantation of
      patients with lymphoma.
AB  - Non-myeloablative (NMA) allogeneic donor SCT for patients with relapsed lymphoma
      is associated with lower treatment-related mortality (TRM). However, the impact
      of conditioning intensity on post transplant infections remains unclear. We
      evaluated infections in 141 consecutive patients with lymphoma who were
      allografted using NMA (n=76) or myeloablative (MA; n=65) conditioning regimens.
      Using infection incidence density per 1000 patient days, we accounted for all
      infectious episodes during the first post transplant year. Before neutrophil
      engraftment, the NMA cohort had a 53% lower rate of bacterial infection (relative
      risk=0.47; P=0.06), whereas after engraftment the density of bacterial infections
      was similar in the two groups. In the first month, both invasive fungal
      infections and viral infections were twofold less frequent (P=0.22; P=0.06) in
      NMA patients. Late viral and fungal infections as well as CMV reactivation were
      infrequent after either conditioning intensity. The 1-year infection-related
      mortality was significantly lower after NMA conditioning (NMA 9% (3-16%) vs MA
      22% (11-40%); P=0.03). NMA allogeneic transplantation for lymphoma patients
      results in substantially fewer early infections and lower infection-related
      deaths, although the similar frequency of later infections suggests that immune
      reconstitution is delayed with either conditioning intensity.

PMID- 18806839
TI  - Signal-to-noise ratio analysis of all-fiber common-path optical coherence
      tomography.
AB  - We present theoretical analysis and experimental verification of the signal to
      noise ratio (SNR) of a common-path interferometer-based optical coherence
      tomography (OCT) system. Based on fully integrated all-fiber implementation of a
      common-path time-domain OCT system, we derived the SNR of the system including
      the effect of beat noise, which turns out to be twice as large as the excess
      noise term. We verified the theoretical SNR through a series of experiments,
      utilizing both controlled phantom and biological samples such as a rat brain with
      tumor and a frog retina. The results showed that the source power and the
      reference reflectivity can be easily controlled to optimize the SNR of OCT
      imaging. We have also analyzed the effect of the fiber delays and the offset in
      the fiber autocorrelator of the common-path OCT system on the overall SNR.

PMID- 18806840
TI  - Simultaneous measurement of multiparameters using a Sagnac interferometer with
      polarization maintaining side-hole fiber.
AB  - A Sagnac interferometer with a section of a polarization maintaining side-hole
      fiber for multiparameter measurement is proposed. The sensor was experimentally
      demonstrated to be sensitive to torsion, temperature, and longitudinal strain,
      simultaneously. The birefringence in the investigated side-hole fiber is induced
      simultaneously by the elliptical shape of a germanium-doped core and by field
      overlap with the air holes surrounding the core. The latter effect is purely
      geometrical and causes high chromatic dispersion of the group birefringence in
      the long wavelength range, which results in a different period of spectral
      interference fringes. A different wavelength response is obtained for each
      interference fringe peak when the fiber is subjected to torsion, temperature, or
      longitudinal strain. A matrix equation for simultaneous measurement of the three
      parameters--torsion, temperature, and longitudinal strain--is also proposed.

PMID- 18806841
TI  - Electromagnetically induced Bragg reflection with a stationary coupling field in
      a buffer rubidium vapor cell.
AB  - An electromagnetically induced Bragg reflection with a stationary coupling field
      in an Rb vapor cell with a 6.67 kPa neon buffer gas was studied. When the
      coupling field was spatially modulated as a stationary wave, a transmission
      reduction of the probe field was observed, while simultaneously a reflected probe
      field was detected in the backward direction. Instead of absorbing a fraction of
      the probe laser in the Rb vapor, the modulated electromagnetically induced
      transparency medium reflected it, corresponding to a Bragg reflection. The
      spectrum in the 5S(1/2)-5P(1/2)Lambda-type system of (87)Rb atoms was
      investigated as a function of the coupling laser frequency detuning, the
      stationary coupling laser power, the vapor cell temperature, and the coupling
      laser power ratio.

PMID- 18806842
TI  - Dispersion measurement of inert gases and gas mixtures at 800 nm.
AB  - Dispersion of femtosecond laser pulses propagating in Ar, He, Kr, N(2), Ne, Xe,
      and their mixtures is measured by spectrally and spatially resolved
      interferometry. By varying the gas pressure in a 4.5 m long tube between 0.05
      mbar and ambient pressure, the first, second, and third order phase derivatives
      of broadband laser pulses are determined at 800 nm under standard conditions. The
      dispersion of gases and gas mixtures obeys the Lorentz-Lorenz formula with an
      accuracy of 0.7%. Based on the measured pressure dependent dispersion values in
      the near infrared and the refractive indices available from the literature for
      the ultraviolet and visible, a pressure dependent Sellmeier-type formula is
      fitted for each gas. These common form, two-term dispersion equations provide an
      accuracy between 4.1x10(-9) (Ne) and 4.3x10(-7) (Xe) for the refractive indices,
      from UV to near IR.

PMID- 18806843
TI  - Electromagnetically induced self-imaging in the Doppler broadening medium.
AB  - Under the condition of electromagnetically induced transparency, self-imaging in
      three-level Lambda-type atoms at normal temperature is studied. The influences of
      the temperature on the position of the self-imaging and the corresponding imaging
      quality are discussed in detail. Numerical results show that, with the increase
      of the temperature, the location of the self-imaging linearly moves away from the
      original object, and the self-imaging quality decreases.

PMID- 18806844
TI  - Phase-difference detection based on a double position sensing detector
      configuration for coherent combination.
AB  - Phase-difference detection based on a double position sensing detector (PSD)
      configuration for coherent combination is proposed in this paper. The exact phase
      difference can be extracted from two PSD signals by using an algorithm, which can
      be used as the driven signal added to the phase modulator for phase-difference
      compensation. Numerical calculation considering practical experimental conditions
      was performed to show that the method is of great potential for coherent
      combination.

PMID- 18806845
TI  - Embedded metal-wire nanograting for a multifunctional optical device.
AB  - In this paper, an embedded metal-wire nanograting was fabricated and used to
      construct a multifunctional optical device. The basic function of the nanograting
      is as a broadband polarizing beam splitter. On the top of the nanograting
      surface, a homogeneity cladding layer was deposited, and metal wires were
      deposited in the grating trench. This multifunctional optical device based on the
      artificial material is designed with a very simple structure, but with the
      functions of a variable optical attenuator, an optical switch, and a variable
      optical power splitter. The experimental result as a variable optical power
      splitter is presented.

PMID- 18806846
TI  - In-line broadband 270 degrees (3lambda/4) chevron four-reflection wave retarders.
AB  - The net differential phase shift Delta(t) introduced between the orthogonal p and
      s linear polarizations after four successive total internal reflections inside an
      in-line chevron dual-Fresnel-rhomb retarder is a function of the first internal
      angle of incidence phi and prism refractive index n. Retardance of 3lambda/4
      (i.e., Delta(t)=270 degrees) is achieved with minimum angular sensitivity when
      phi=45 degrees and n=1.900822. Several optical glasses with this refractive index
      are identified. For Schott glass SF66 the deviation of Delta(t) from 270 degrees
      is < or = 4 degrees over a wavelength range of 0.55 < or = lambda < or = 1.1
      microm in the visible and near-IR spectrum. For a SiC prism, whose totally
      reflecting surfaces are coated with an optically thick MgF(2) film, Delta(t)=270
      degrees at two wavelengths: lambda(1)=0.707 microm and lambda(2)=4.129 microm.
      This coated prism has a maximum retardance error of approximately 5 degrees over
      > three octaves (0.5 to 4.5 microm) in the visible, near-, and mid-IR spectral
      range. Another mid-IR 3lambda/4 retarder uses a Si prism, which is coated by an
      optically thick silicon oxynitride film of the proper composition, to achieve
      retardance that differs from 270 degrees by < 0.5 degrees over the 3-5 microm
      spectral range.

PMID- 18806847
TI  - Optically multiplexed multi-gas detection using quantum cascade laser
      photoacoustic spectroscopy.
AB  - We report high-throughput, nondispersive optical multiplexing of laser beams
      using a scanning galvanometer. We have utilized this technique for multispecies
      trace-gas detection using multiple quantum cascade laser photoacoustic
      spectroscopy. We demonstrate switching from one laser to another in less than 1
      s, a performance level needed for a comprehensive multispecies sensor, and a high
      signal-to-noise ratio detection of five gaseous components, NH(3), NO(2),
      dimethyl methyl phosphonate (DMMP, a simulant for nerve agents), acetone, and
      ethylene glycol, in a room air gas mixture containing approximately 3 ppb of
      NH(3), approximately 8 ppb of NO(2), approximately 20 ppb of DMMP, approximately
      30 ppb of acetone, and approximately 40 ppb of ethylene glycol.

PMID- 18806848
TI  - Refractive index and extinction coefficient determination of an absorbing thin
      film by using the continuous wavelet transform method.
AB  - We present the continuous wavelet transform (CWT) method for determining the
      dispersion curves of the refractive index and extinction coefficient of absorbing
      thin films by using the transmittance spectrum in the visible and near infrared
      regions at room temperature. The CWT method is performed on the transmittance
      spectrum of an a - Si(1-x)C(x):H film, and the refractive index and extinction
      coefficient of the film are continuously determined and compared with the results
      of the envelope and fringe counting methods. Also the noise filter property of
      the method is depicted on a theoretically generated noisy signal. Finally, the
      error analyses of the CWT, envelope, and fringe counting methods are performed.

PMID- 18806849
TI  - Decay time characteristics of La2O2S:Eu and La2O2S:Tb for use within an optical
      sensor for human skin temperature measurement.
AB  - We focus on the development of a remote temperature sensing technology, i.e., an
      optical laser-based sensor, using thermographic phosphors for medical
      applications, particularly within an electromagnetically hostile magnetic
      resonance imaging (MRI) environment. A MRI scanner uses a strong magnetic field
      and radio waves to generate images of the inside of the body. The quality of the
      image improves with increasing magnetic resonance; however, the drawback of
      applying a greater magnetic strength is the inducement of heat into the body
      tissue. Therefore, monitoring the patient's temperature inside MRI is vital, but
      until now, a practical solution for temperature measurement did not exist. We
      show europium doped lanthanum oxysulphide (La(2)O(2)S:Eu) and terbium doped
      lanthanum oxysulphide (La(2)O(2)S:Tb) are both temperature sensitive to a low
      temperature range of 10-50 degrees C when under ultraviolet (UV) excitation. The
      emission spectra and decay time characteristics of these phosphors were
      demonstrated. The results indicate that La(2)O(2)S:Eu has a quenching rate of
      13.7 m degrees C(-1) and 4 m degrees C(-1) at 512 nm and 538 nm, respectively. In
      addition, La(2)O(2)S:Tb has a lower quenching rate of 4.19 m degrees C(-1) at 548
      nm due to its faster decay time.

PMID- 18806850
TI  - Measurement of two-dimensional small angle deviation with a prism interferometer.
AB  - A new technique for the measurement of two-dimensional small angular deviation is
      presented. A compound prism, which effectively produces a combination of two
      right-angled prisms in orthogonal directions, and plane reference surfaces have
      been utilized for the measurement of the orthogonal components of the angular
      tilt of an incident plane wavefront. Each orthogonal component of the angular
      tilt is separately measured from the angular rotation of the resultant wedge
      fringes between two plane wavefronts generated due to splitting of the incident
      plane wavefront by the corresponding set of right-angled prism and plane
      reference surface. The technique is shown to have high sensitivity for the
      measurement of small angle deviation. A monolithic prism interferometer, which is
      practically insensitive to vibration, is also proposed. Results obtained for the
      measurement of a known tilt angle are presented.

PMID- 18806851
TI  - Power losses in deformed graded-index polymer optical fibers.
AB  - We investigate the power losses in bent and elongated graded-index polymer
      optical fibers (GI POFs). The variations of power losses in deformed GI POFs for
      various radii of curvature and elongations are measured. A simple tensile test
      result is used to calculate the average plastic energy density (APED) in a
      deformed GI POF at various elongations. The results indicate that the APED
      accumulated in a deformed GI POF can be considered as a key index to study the
      power loss in POF. Based on the experimental results, a curve-fitted equation is
      proposed to estimate the power loss using the APED for various radii of
      curvature. The maximum difference between the proposed equation and the
      experimental results is less than 3% for the deformed GI POFs.

PMID- 18806852
TI  - Achromatic interfero-coronagraph with two common-path interferometers in tandem.
AB  - To attain deeper nulling for an extended incoherent star disk a scheme for an
      achromatic interfero-coronagraph, incorporating two common-path interferometers
      in tandem, is proposed. Analytical and numerical predictions of the performance,
      which are in reasonably good agreement, are presented. The predicted performance
      improvement, by using two interferometers in tandem, is demonstrated by a
      preliminary experiment. A star coronagraph based on the proposed technique has
      the possibility to reach a 10(-10) achromatic nulling contrast for an almost 10(
      2) lambda/D effective source size.

PMID- 18806853
TI  - Thin-type integral imaging method with an organic light emitting diode panel.
AB  - A thin and lensless two-dimensional (2D) to three-dimensional (3D) convertible
      display based on integral imaging using an organic light emitting diode (OLED)
      panel as a direct emissive light source is proposed with improved optical
      efficiency. A point light source array for 2D-3D convertible display is formed on
      the surface light source, i.e., the OLED panel. However, a blurring effect and
      color separation result from the finite (nonzero) size of point light sources
      since each point light source is generated by a pixel of the OLED panel.
      Simulation results for a blurring effect and color separation in terms of rays
      from a light source with finite size is presented. The proposed system has a thin
      structure and simple convertibility because it does not need any additional
      optical element to provide 2D-3D convertibility.

PMID- 18806854
TI  - Calculation of the coupling coefficient in strained step index plastic optical
      fibers.
AB  - The coupling coefficient in a strained step index plastic optical fiber is
      determined using our recent simplified method. This enabled the calculation of
      the length z(s) at which the steady-state distribution (SSD) is achieved. Results
      are in good agreement with measurements reported earlier. The strained fiber
      shows a much stronger mode coupling than the unstrained one of the same type.
      Consequently, the fiber length for achieving the SSD is much shorter for strained
      than unstrained fibers.

PMID- 18806855
TI  - Bismuth activated alumosilicate optical fibers fabricated by surface-plasma
      chemical vapor deposition technology.
AB  - Plasma chemical technology is experimentally applied to the fabrication of a Bi
      activated alumosilicate-core pure-silica-cladding fiber preform. To the best of
      our knowledge, this is the first time this technology has been applied in this
      way. We measure gain efficiency at pumping by a 1058 nm wavelength Yb fiber laser
      in a piece of a newly obtained fiber 20 m in length within 100-1200 nm
      wavelengths band. The gain efficiency reaches as high as 0.2 dB/mW. Bi-activated
      alumosilicate-core pure-silica-cladding fiber that is not more than 12 m in
      length serves a basis for a 1 W output power fiber laser emitting at the
      wavelength of 1160 nm with 8% slope efficiency. We also measure the
      photoluminescence spectrum and kinetics of Bi centers responsible for laser
      emission under the excitation of 193 nm wavelength ArF laser pulses.

PMID- 18806856
TI  - Characteristics of aerosol optical properties in pollution and Asian dust
      episodes over Beijing, China.
AB  - Aerosol optical properties were continuously measured with the National Institute
      for Environmental Studies (NIES) compact Raman lidar over Beijing, China, from 15
      to 31 December 2007. The results indicated that in a moderate pollution episode,
      the averaged aerosol extinction below 1 km height was 0.39+/-0.15 km(-1) and the
      lidar ratio was 60.8+/-13.5 sr; in heavy pollution episode, they were 1.97+/-0.91
      km(-1) and 43.7+/-8.3 sr; in an Asian dust episode, they were 0.33+/-0.11 km(-1)
      and 38.3+/-9.8 sr. The total depolarization ratio was mostly below 10% in the
      pollution episode, whereas it was larger than 20% in the Asian dust episode. The
      distinct characteristics of aerosol optical properties in moderate and heavy
      pollution episodes were attributed to the difference in air mass trajectory and
      the ambient atmospheric conditions such as relative humidity.

PMID- 18806857
TI  - Laser Doppler vibrometer employing active frequency feedback.
AB  - We present a heterodyne Michelson interferometer for vibration measurement in
      which feedback is used to obviate the need to unwrap phase data. The Doppler
      shift of a vibrating target mirror is sensed interferometrically and compensated
      by means of a voltage-controlled oscillator driving an acousto-optic modulator.
      For frequencies within the servo bandwidth, the oscillator control voltage
      provides a direct measurement of the target velocity. Outside the servo
      bandwidth, phase-sensitive detection is used to evaluate high-frequency
      displacements. This approach is of great interest for the frequently-occurring
      situation where vibration amplitudes at low frequency exceed an optical
      wavelength, but knowledge of the vibration spectrum at high frequency is
      important as well.

PMID- 18806858
TI  - Littrow angle method to remove alignment errors in grating pulse compressors.
AB  - An alignment method for pulse-compression gratings that obviates the need to
      place the gratings at normal incidence to remove grating-tip error is proposed.
      Grating-tip and groove-orientation errors are removed using two alignment
      wavelengths in a manner analogous to a laser-beam pointing and centering
      procedure entirely at the respective Littrow angles for the two wavelengths. By
      choosing wavelengths with Littrow angles close to the use angle of the grating,
      the residual tip and groove-orientation errors that may be introduced when the
      grating mount is tilted to its use angle are reduced. This method has greatly
      facilitated the alignment of the OMEGA Extended Performance (EP) large-aperture
      pulse compressors, thereby reducing residual pulse-front tilt caused by
      nonparallel gratings. OMEGA EP is a high-energy, petawatt-class laser at the
      University of Rochester's Laboratory for Laser Energetics. A numerical simulation
      of the alignment procedure is presented.

PMID- 18806859
TI  - Comparative evaluation of two simple diffuse reflectance models for biological
      tissue applications.
AB  - We present a comparative evaluation of two simple diffuse reflectance models for
      biological tissue applications. One model is based on a widely accepted and used
      in biomedical optics implementation of diffusion theory, and the other one is
      based on a semiempirical approach derived from basic physical principles. We test
      the models on tissue phantoms and on human skin, utilizing a standard six-around
      one optical fiber probe for light delivery and collection. We show that both
      models are suitable for use with an optical fiber probe and illustrate the
      potential, applicability, and validity range of the models.

PMID- 18806860
TI  - Inspection of commercial optical devices for data storage using a three Gaussian
      beam microscope interferometer.
AB  - Recently, an interferometric profilometer based on the heterodyning of three
      Gaussian beams has been reported. This microscope interferometer, called a three
      Gaussian beam interferometer, has been used to profile high quality optical
      surfaces that exhibit constant reflectivity with high vertical resolution and
      lateral resolution near lambda. We report the use of this interferometer to
      measure the profiles of two commercially available optical surfaces for data
      storage, namely, the compact disk (CD-R) and the digital versatile disk (DVD-R).
      We include experimental results from a one-dimensional radial scan of these
      devices without data marks. The measurements are taken by placing the devices
      with the polycarbonate surface facing the probe beam of the interferometer. This
      microscope interferometer is unique when compared with other optical measuring
      instruments because it uses narrowband detection, filters out undesirable noisy
      signals, and because the amplitude of the output voltage signal is basically
      proportional to the local vertical height of the surface under test, thus
      detecting with high sensitivity. We show that the resulting profiles, measured
      with this interferometer across the polycarbonate layer, provide valuable
      information about the track profiles, making this interferometer a suitable tool
      for quality control of surface storage devices.

PMID- 18806861
TI  - Celestial body irradiance determination from an underfilled satellite radiometer:
      application to albedo and thermal emission measurements of the Moon using CERES.
AB  - The Clouds and the Earth's Radiant Energy System (CERES) is a program that
      measures the Earth radiation budget (ERB) from two polar orbiting satellite
      platforms. CERES radiometers are designed to make stable broadband measurements
      of scattered solar and emitted thermal radiative flux leaving Earth with an
      accuracy of 1% or better. Using versatile and programmable scan modes, it is also
      possible for every CERES instrument to view the Moon on each orbit. However,
      until now, it has not been possible to derive absolute measurements of lunar
      irradiance using CERES because the Moon's disk fills only 10% of the telescope
      field of view. This work presents a method of integrating CERES raster-scan data
      in order to obtain a measurement of the average scattered solar and emitted
      thermal radiance from the entire lunar disk. The technique results in excellent
      agreement between CERES instruments on different satellites as to lunar albedo
      and emitted thermal flux. The average broadband Moon albedo is measured by CERES
      at a value of 0.1362 (+/-2-3%) when normalized to a static lunar phase angle of 7
      degrees using the U.S. Geological Survey lunar irradiance Robotic Lunar
      Observatory model. The method for the first time also yields very accurate
      measurements of the thermal irradiance emitted from the Moon. These suggest an
      average long-wave flux of 977 Wm(-2) (+/-2-3% at 7 degrees phase), implying an
      approximate mean surface temperature of around 92 degrees C. Statistical analysis
      on available data suggests that a CERES instrument performing monthly lunar
      measurements could utilize the Moon as a stability target and reduce calibration
      drifts to 0.3% per decade or less within an instrument's lifetime. Given the
      success of the technique, a solar calibration system is proposed that will allow
      precise tracking of an ERB instrument's optical degradation using the Sun.

PMID- 18806862
TI  - Design and evaluation of a THz time domain imaging system using standard optical
      design software.
AB  - A terahertz (THz) time domain imaging system is analyzed and optimized with
      standard optical design software (ZEMAX). Special requirements to the
      illumination optics and imaging optics are presented. In the optimized system,
      off-axis parabolic mirrors and lenses are combined. The system has a numerical
      aperture of 0.4 and is diffraction limited for field points up to 4 mm and
      wavelengths down to 750 microm. ZEONEX is used as the lens material. Higher
      aspherical coefficients are used for correction of spherical aberration and
      reduction of lens thickness. The lenses were manufactured by ultraprecision
      machining. For optimization of the system, ray tracing and wave-optical methods
      were combined. We show how the ZEMAX Gaussian beam analysis tool can be used to
      evaluate illumination optics. The resolution of the THz system was tested with a
      wire and a slit target, line gratings of different period, and a Siemens star.
      The behavior of the temporal line spread function can be modeled with the
      polychromatic coherent line spread function feature in ZEMAX. The spectral and
      temporal resolutions of the line gratings are compared with the respective
      modulation transfer function of ZEMAX. For maximum resolution, the system has to
      be diffraction limited down to the smallest wavelength of the spectrum of the THz
      pulse. Then, the resolution on time domain analysis of the pulse maximum can be
      estimated with the spectral resolution of the center of gravity wavelength. The
      system resolution near the optical axis on time domain analysis of the pulse
      maximum is 1 line pair/mm with an intensity contrast of 0.22. The Siemens star is
      used for estimation of the resolution of the whole system. An eight channel
      electro-optic sampling system was used for detection. The resolution on time
      domain analysis of the pulse maximum of all eight channels could be determined
      with the Siemens star to be 0.7 line pairs/mm.

PMID- 18806863
TI  - Intersatellite range monitoring using optical interferometry.
AB  - We report on an interferometer designed to provide 1-10 nm/square root(Hz)
      displacement measurement resolution, in the range 0.01 Hz to 1 Hz, while in low
      Earth orbit. The interferometer comprises two units, each with its own laser and
      in separate satellites, which would be in the same orbit separated by
      approximately 50 km. We discuss the requirements on the interferometer subsystem
      and describe the optical transponder distance measurement, including a phase
      locking method to generate a heterodyne beat signal between the two lasers.
      Design, fabrication, and testing of a "flightlike" engineering model
      interferometer is outlined, and results from environmental and performance tests
      are reported.

PMID- 18806864
TI  - Infrared Mueller matrix acquisition and preprocessing system.
AB  - An analog Mueller matrix acquisition and preprocessing system (AMMS) was
      developed for a photopolarimetric-based sensor with 9.1-12.0 microm optical
      bandwidth, which is the middle infrared wavelength-tunable region of sensor
      transmitter and "fingerprint" spectral band for chemical-biological (analyte)
      standoff detection. AMMS facilitates delivery of two alternate polarization
      modulated CO(2) laser beams onto subject analyte that excite/relax molecular
      vibrational resonance in its analytic mass, primes the photoelastic-modulation
      engine of the sensor, establishes optimum throughput radiance per backscattering
      cross section, acquires Mueller elements modulo two laser beams in hexadecimal
      format, preprocesses (normalize, subtract, filter) these data, and formats the
      results into digitized identification metrics. Feed forwarding of formatted
      Mueller matrix metrics through an optimally trained and validated neural network
      provides pattern recognition and type classification of interrogated analyte.

PMID- 18806865
TI  - Laser Doppler field sensor for high resolution flow velocity imaging without
      camera.
AB  - In this paper we present a laser sensor for highly spatially resolved flow
      imaging without using a camera. The sensor is an extension of the principle of
      laser Doppler anemometry (LDA). Instead of a parallel fringe system, diverging
      and converging fringes are employed. This method facilitates the determination of
      the tracer particle position within the measurement volume and leads to an
      increased spatial and velocity resolution compared to conventional LDA. Using a
      total number of four fringe systems the flow is resolved in two spatial
      dimensions and the orthogonal velocity component. Since no camera is used, the
      resolution of the sensor is not influenced by pixel size effects. A spatial
      resolution of 4 microm in the x direction and 16 microm in the y direction and a
      relative velocity resolution of 1x10(-3) have been demonstrated up to now. As a
      first application we present the velocity measurement of an injection nozzle
      flow. The sensor is also highly suitable for applications in nano- and
      microfluidics, e.g., for the measurement of flow rates.

PMID- 18806866
TI  - Ultrafast low-threshold all-optical switch implemented by arrays of ring
      resonators coupled to a Mach-Zehnder interferometer arm: based on 2D photonic
      crystals.
AB  - Using an array of m x n nonlinear ring resonators (m = 1, 3, 5, and n = 1, 2, 3)
      coupled to the upper arm of a Mach-Zehnder interferometer (MZI), we have proposed
      an all-optical switch structure. Using a 5 x 3 array, we have shown the
      possibility of designing an all-optical switching device with a threshold
      intensity as low as 15 mW/m(2) and switching window of approximately 35 ps. While
      using m x 1 arrays, we have achieved switching windows smaller than 10 ps, at the
      expense of higher switching thresholds, ranging from 37 to 55 mW/m(2). The whole
      structure is based on a square lattice photonic crystal of lattice constant a =
      600 nm, formed by rods of radius r = 90 nm in an air background. The linear rods'
      refractive index is taken to be the same as that of Si(0.75)Ge(0.25); i.e., n(r)
      = 3.6, whereas the nonlinear rod's refractive index and Kerr index parameter are
      taken to be n(0) = 1.4 and n(2) = 10(-14) m(2)/W. The center wavelength at which
      the nonlinear rings are designed to make the resonance is taken to be lambda(0) =
      1550 nm in free space.

PMID- 18806867
TI  - Limitations of self-phase-modulation-based tunable delay system for all-optical
      buffer design.
AB  - The distortion, noise, and bit-delay performance of a self-phase-modulation-based
      tunable delay system are analyzed. The pulse amplification required for achieving
      large spectral broadening results in large amplifier noise. We quantify the
      resulting delay versus signal-to-noise ratio trade-off. We demonstrate that for
      high bit rates it is difficult to achieve both large bit delay and good data
      fidelity. We find that for a given bit rate, reducing the duty cycle improves the
      fractional bit delay. For a duty cycle of 16%, a maximum bit delay of 15 bits is
      achieved.

PMID- 18806868
TI  - Hole-assisted lightguide fibers with small negative dispersion and low dispersion
      slope.
AB  - A nonzero dispersion shifted fiber design based on hole-assisted lightguide fiber
      is presented. The proposed fiber has low dispersion slope around -0.01 ps/nm(2)
      km and small negative dispersion values over the wavelength range from 1530 to
      1620 nm. It can be used as a transmission medium for a long-haul dense wavelength
      division-multiplexed system.

PMID- 18806869
TI  - Feasibility of laparoscopic portal vein ligation prior to major hepatectomy.
AB  - BACKGROUND: Patients noted to have an inadequate future liver remnant on pre
      operative volumetric assessment are considered to be candidates for portal vein
      embolization (PVE). A subset of patients undergo laparoscopic intervention prior
      to PVE for staging purposes or to address the primary in Stage IV colon cancer.
      These patients usually undergo PVE as a subsequent additional procedure by the
      transhepatic route. The aim of this study was to assess the feasibility of portal
      vein ligation by the laparoscopic approach in suitable patients. MATERIALS AND
      METHODS: A retrospective review of a prospectively maintained database was
      performed to identify patients that underwent laparoscopic portal vein ligation
      (LPVL). The demographic, clinical, radiographic, operative and volumetric details
      were collected to determine the feasibility of portal vein ligation. RESULTS: A
      total of nine patients underwent LPVL as part of a two stage procedure in
      preparation for subsequent major hepatectomy. With a median age of 67 yrs, the
      diagnoses included: colorectal metastasis (five patients), cholangiocarcinoma
      (three patients) and hepatocellular carcinoma (one patient). The ligation
      involved the right portal vein in all and was performed with silk ligature (seven
      patients) and clips (two patients). Volumetric data was available in six patients
      which showed a mean increase from 209.1 cc+/-97.76 to 495.83 cc+/-310.91
      (increase by 181.5%) In two patients, inadequate hypertrophy mandated later
      embolization by percutaneous technique. Five patients underwent subsequent major
      hepatic resection as planned. The remaining four patients were noted to have
      progression of disease that precluded the planned procedure. There were no
      complications associated with LPVL. CONCLUSIONS: LPVL is feasible and can be
      safely performed. In a select group of patients, it may be considered as an
      alternative to subsequent embolization and thereby potentially absolve the need
      for an additional procedure with its attendant complications.

PMID- 18806870
TI  - Posterior auricular perichondrial cutaneous graft combined with cartilage strip
      in nostril reconstruction.
AB  - OBJECTIVE: Reconstruction of alar structures of the nose remains difficult. The
      result has to be not only functional but also aesthetic. Different solutions to
      reconstruct alar defects are feasible. A good result that meets the specific
      demands on stability, aesthetics, and stable architecture without shrinkage of
      the area is not easily achieved. METHOD: A perichondrial cutaneous graft (PCCG),
      a graft consisting of a perichondral layer, fatty tissue, and skin that is
      harvested retroauriculary, is combined with an attached cartilage strip. CASE
      RESULT: A 72-year-old patient suffering from basal cell carcinoma of the ala of
      the nose underwent the reconstructive procedure with a good result in 1 year in
      terms of stability, color match, and graft take. CONCLUSION: First, a strip of
      cartilage had been included in a PCCG where tumor resection required sacrifice of
      more than 50% of the alar rim. The case shows that one can consider a cartilage
      strip-enhanced PCCG graft to reconstruct alar defects.

PMID- 18806871
TI  - Assessment of the distal extent of the A1 pulley release: a new technique.
AB  - OBJECTIVE: Sharp division of the A1 pulley is a time-honored technique for the
      treatment of flexor tendon entrapment; however, this procedure is not without
      complications. The anatomy of the A1 pulley system has been carefully
      investigated. Knowledge of superficial anatomic landmarks can assist with
      demarcating the distal edge of the A1 pulley and prevent damage to the critical
      A2 pulley. METHODS: Nine fresh cadaveric hands were dissected with the aid of
      loupe magnification. On the basis of known anatomic landmarks of the proximal
      portion of the cruciate (C0) pulley, percutaneous placement of a 25-gauge needle
      5 mm proximal to the palmar digital crease marked the distal extent of the
      trigger finger release. Sharp division of the A1 pulley was performed with a
      scalpel until the needle was encountered, thus completing the release. RESULTS: A
      complete release of the pulley was achieved in all specimens with preservation of
      the A2 pulley. No digital nerve or artery injuries were noted with open
      inspection of the flexor sheath. CONCLUSION: Percutaneous marking of the distal
      extent of the A1 pulley is a safe and reliable method that not only ensures
      complete release of the A1 pulley but also preserves the A2 pulley. The placement
      of a small gauge needle adds no morbidity to this minimally invasive technique.

PMID- 18806872
TI  - Epstein-Barr virus associated modulation of Wnt pathway is not dependent on
      latent membrane protein-1.
AB  - Previous studies have indicated that Epstein-Barr virus (EBV) can modulate the
      Wnt pathway in virus-infected cells and this effect is mediated by EBV-encoded
      oncogene latent membrane protein 1 (LMP1). Here we have reassessed the role of
      LMP1 in regulating the expression of various mediators of the canonical Wnt
      cascade. Contradicting the previous finding, we found that the levels of E
      cadherin, beta-catenin, Glycogen Synthase Kinase 3ss (GSK3beta), axin and alpha
      catenin were not affected by the expression of LMP1 sequences from normal B cells
      or nasopharyngeal carcinoma. Moreover, we also show that LMP1 expression had no
      detectable effect on the E-cadherin and beta-catenin interaction and did not
      induce transcriptional activation of beta-catenin. Taken together these studies
      demonstrate that EBV-mediated activation of Wnt pathway is not dependent on the
      expression of LMP1.

PMID- 18806873
TI  - ZNF198 stabilizes the LSD1-CoREST-HDAC1 complex on chromatin through its MYM-type
      zinc fingers.
AB  - Histone modifications in chromatin regulate gene expression. A transcriptional co
      repressor complex containing LSD1-CoREST-HDAC1 (termed LCH hereafter for
      simplicity) represses transcription by coordinately removing histone
      modifications associated with transcriptional activation. RE1-silencing
      transcription factor (REST) recruits LCH to the promoters of neuron-specific
      genes, thereby silencing their transcription in non-neuronal tissues. ZNF198 is a
      member of a family of MYM-type zinc finger proteins that associate with LCH.
      Here, we show that ZNF198-like proteins are required for the repression of E
      cadherin (a gene known to be repressed by LSD1), but not REST-responsive genes.
      ZNF198 binds preferentially to the intact LCH ternary complex, but not its
      individual subunits. ZNF198- and REST-binding to the LCH complex are mutually
      exclusive. ZNF198 associates with chromatin independently of LCH. Furthermore,
      modification of HDAC1 by small ubiquitin-like modifier (SUMO) in vitro weakens
      its interaction with CoREST whereas sumoylation of HDAC1 stimulates its binding
      to ZNF198. Finally, we mapped the LCH- and HDAC1-SUMO-binding domains of ZNF198
      to tandem repeats of MYM-type zinc fingers. Therefore, our results suggest that
      ZNF198, through its multiple protein-protein interaction interfaces, helps to
      maintain the intact LCH complex on specific, non-REST-responsive promoters and
      may also prevent SUMO-dependent dissociation of HDAC1.

PMID- 18806874
TI  - Preventing mitochondrial fission impairs mitochondrial function and leads to loss
      of mitochondrial DNA.
AB  - Mitochondria form a highly dynamic tubular network, the morphology of which is
      regulated by frequent fission and fusion events. However, the role of
      mitochondrial fission in homeostasis of the organelle is still unknown. Here we
      report that preventing mitochondrial fission, by down-regulating expression of
      Drp1 in mammalian cells leads to a loss of mitochondrial DNA and a decrease of
      mitochondrial respiration coupled to an increase in the levels of cellular
      reactive oxygen species (ROS). At the cellular level, mitochondrial dysfunction
      resulting from the lack of fission leads to a drop in the levels of cellular ATP,
      an inhibition of cell proliferation and an increase in autophagy. In conclusion,
      we propose that mitochondrial fission is required for preservation of
      mitochondrial function and thereby for maintenance of cellular homeostasis.

PMID- 18806875
TI  - Protein isoaspartate methyltransferase prevents apoptosis induced by oxidative
      stress in endothelial cells: role of Bcl-Xl deamidation and methylation.
AB  - BACKGROUND: Natural proteins undergo in vivo spontaneous post-biosynthetic
      deamidation of specific asparagine residues with isoaspartyl formation.
      Deamidated-isomerized molecules are both structurally and functionally altered.
      The enzyme isoaspartyl protein carboxyl-O-methyltransferase (PCMT; EC 2.1.1.77)
      has peculiar substrate specificity towards these deamidated proteins. It
      catalyzes methyl esterification of the free alpha-carboxyl group at the
      isoaspartyl site, thus initiating the repair of these abnormal proteins through
      the conversion of the isopeptide bond into a normal alpha-peptide bond.
      Deamidation occurs slowly during cellular and molecular aging, being accelerated
      by physical-chemical stresses brought to the living cells. Previous evidence
      supports a role of protein deamidation in the acquisition of susceptibility to
      apoptosis. Aim of this work was to shed a light on the role of PCMT in apoptosis
      clarifying the relevant mechanism(s). METHODOLOGY/PRINCIPAL FINDINGS: Endothelial
      cells transiently transfected with various constructs of PCMT, i.e.
      overexpressing wild type PCMT or negative dominants, were used to investigate the
      role of protein methylation during apoptosis induced by oxidative stress
      (H(2)O(2); 0.1-0.5 mM range). Results show that A) Cells overexpressing "wild
      type" human PCMT were resistant to apoptosis, whereas overexpression of antisense
      PCMT induces high sensitivity to apoptosis even at low H(2)O(2) concentrations.
      B) PCMT protective effect is specifically due to its methyltransferase activity
      rather than to any other non-enzymatic interactions. In fact negative dominants,
      overexpressing PCMT mutants devoid of catalytic activity do not prevent
      apoptosis. C) Cells transfected with antisense PCMT, or overexpressing a PCMT
      mutant, accumulate isoaspartyl-containing damaged proteins upon H(2)O(2)
      treatment. Proteomics allowed the identification of proteins, which are both PCMT
      substrates and apoptosis effectors, whose deamidation occurs under oxidative
      stress conditions leading to programmed cell death. These proteins, including
      Hsp70, Hsp90, actin, and Bcl-xL, are recognized and methylated by PCMT, according
      to the general repair mechanism of this methyltransferase.
      CONCLUSION/SIGNIFICANCE: Apoptosis can be modulated by "on/off" switch
      partitioning the amount of specific protein effectors, which are either in their
      active (native) or inactive (deamidated) molecular forms. Deamidated proteins can
      also be functionally restored through methylation. Bcl-xL provides a case for the
      role of PCMT in the maintenance of functional stability of this antiapoptotic
      protein.

PMID- 18806876
TI  - Somatic 'soluble' adenylyl cyclase isoforms are unaffected in Sacy tm1Lex/Sacy
      tm1Lex 'knockout' mice.
AB  - BACKGROUND: Mammalian Soluble adenylyl cyclase (sAC, Adcy10, or Sacy) represents
      a source of the second messenger cAMP distinct from the widely studied, G protein
      regulated transmembrane adenylyl cyclases. Genetic deletion of the second through
      fourth coding exons in Sacy(tm1Lex)/Sacy(tm1Lex) knockout mice results in a male
      sterile phenotype. The absence of any major somatic phenotype is inconsistent
      with the variety of somatic functions identified for sAC using pharmacological
      inhibitors and RNA interference. PRINCIPAL FINDINGS: We now use immunological and
      molecular biological methods to demonstrate that somatic tissues express a
      previously unknown isoform of sAC, which utilizes a unique start site, and which
      'escapes' the design of the Sacy(tm1Lex) knockout allele.
      CONCLUSIONS/SIGNIFICANCE: These studies reveal increased complexity at the sAC
      locus, and they suggest that the known isoforms of sAC play a unique function in
      male germ cells.

PMID- 18806877
TI  - Induction of pluripotent protective immunity following immunisation with a
      chimeric vaccine against human cytomegalovirus.
AB  - Based on the life-time cost to the health care system, the Institute of Medicine
      has assigned the highest priority for a vaccine to control human cytomegalovirus
      (HCMV) disease in transplant patients and new born babies. In spite of numerous
      attempts successful licensure of a HCMV vaccine formulation remains elusive. Here
      we have developed a novel chimeric vaccine strategy based on a replication
      deficient adenovirus which encodes the extracellular domain of gB protein and
      multiple HLA class I & II-restricted CTL epitopes from HCMV as a contiguous
      polypeptide. Immunisation with this chimeric vaccine consistently generated
      strong HCMV-specific CD8(+) and CD4(+) T-cells which co-expressed IFN-gamma and
      TNF-alpha, while the humoral response induced by this vaccine showed strong virus
      neutralizing capacity. More importantly, immunization with adenoviral chimeric
      vaccine also afforded protection against challenge with recombinant vaccinia
      virus encoding HCMV antigens and this protection was associated with the
      induction of a pluripotent antigen-specific cellular and antibody response.
      Furthermore, in vitro stimulation with this adenoviral chimeric vaccine rapidly
      expanded multiple antigen-specific human CD8(+) and CD4(+) T-cells from healthy
      virus carriers. These studies demonstrate that the adenovirus chimeric HCMV
      vaccine provides an excellent platform for reconstituting protective immunity to
      prevent HCMV diseases in different clinical settings.

PMID- 18806878
TI  - Quality of care for HIV infection provided by Ryan White Program-supported versus
      Non-Ryan White Program-supported facilities.
AB  - BACKGROUND: The Ryan White HIV/AIDS Care Act (now the Treatment Modernization
      Act; Ryan White Program, or RWP) is a source of federal public funding for HIV
      care in the United States. The Health Services and Resources Administration
      requires that facilities or providers who receive RWP funds ensure that HIV
      health services are accessible and delivered according to established HIV-related
      treatment guidelines. We used data from population-based samples of persons in
      care for HIV infection in three states to compare the quality of HIV care in
      facilities supported by the RWP, with facilities not supported by the RWP.
      METHODOLOGY/PRINCIPAL FINDINGS: Within each area (King County in Washington
      State; southern Louisiana; and Michigan), a probability sample of patients
      receiving care for HIV infection in 1998 was drawn. Based on medical records
      abstraction, information was collected on prescription of antiretroviral therapy
      according to treatment recommendations, prescription of prophylactic therapy, and
      provision of recommended vaccinations and screening tests. We calculated
      population-level estimates of the extent to which HIV care was provided according
      to then-current treatment guidelines in RWP-supported and non-RWP-supported
      facilities. For all treatment outcomes analyzed, the compliance with care
      guidelines was at least as good for patients who received care at RWP-supported
      (vs non-RWP supported) facilities. For some outcomes in some states, delivery of
      recommended care was significantly more common for patients receiving care in RWP
      supported facilities: for example, in Louisiana, patients receiving care in RWP
      supported facilities were more likely to receive indicated prophylaxis for
      Pneumocystis jirovecii pneumonia and Mycobacterium avium complex, and in all
      three states, women receiving care in RWP-supported facilities were more likely
      to have received an annual Pap smear. CONCLUSIONS/SIGNIFICANCE: The quality of
      HIV care provided in 1998 to patients in RWP-supported facilities was of
      equivalent or better quality than in non-RWP supported facilities; however, there
      were significant opportunities for improvement in all facility types. Data from
      population-based clinical outcomes surveillance data can be used as part of a
      broader strategy to evaluate the quality of publicly-supported HIV care.

PMID- 18806879
TI  - Mechanism of mitomycin-induced apoptosis in cultured corneal endothelial cells.
AB  - PURPOSE: Previous studies have indicated that improper use of mitomycin C (MMC)
      caused cytotoxicity in corneal endothelial cells. The aim of the present study
      was to investigate whether MMC induces cellular apoptosis in corneal endothelial
      cells and to determine the mechanism by which this may occur. METHODS: Porcine
      corneal endothelial cells were acquired from primary culture. Cellular damage and
      caspase pathway were estimated with a MTT (3-[4,5-dimethylthiazol-2-yl]-2,5
      diphenyl tetrazolium bromide) assay. The apoptotic characteristics were detected
      by means of flow cytometry, the TUNEL (terminal deoxyribonucleotidyl-transferase
      (TdT)-mediated deoxyuridine-5'-triphosphate-digoxigenin (dUTP) nick-end labeling)
      test, immunofluorescent staining, and western blotting. RESULTS: The results
      indicated that MMC was toxic to corneal endothelial cells in a time-dependent and
      dose-dependent manner. Pretreatment with a general caspase inhibitor (Z-VAD-FMK),
      a caspase-8 inhibitor (Z-IETD-FMK), and a caspase-9 inhibitor (Z-LEHD-FMK)
      reversed MMC-induced cellular damage. Following exposure to MMC, a change in the
      mitochondrial membrane potential was positively detected by flow cytometric assay
      with MitoLight dye while cellular cytochrome c that was released from the
      mitochondria to the cytoplasm was detected by immunofluorescent staining. A
      positive TUNEL test revealed that cellular DNA apoptosis had occurred following
      exposure to 0.001 and 0.01 mg/ml MMC for 24 h. Positive annexin V-FITC, and
      negative propidium iodide (PI) staining indicated that the cellular plasma
      membrane underwent apoptosis following 0.001 mg/ml MMC exposure for 24 h. Western
      blot assay demonstrated down-regulation of the Bcl-2 protein and upregulation of
      the p53 and p21 proteins, which were all involved in apoptosis induced by MMC.
      CONCLUSIONS: These results indicate that mitomycin-induced cellular apoptosis in
      corneal endothelial cells may be mediated through caspase-8, caspase-9, and the
      mitochondrial regulated pathways as well as through upregulation of p53-dependent
      and p21-dependent signal transduction pathways.

PMID- 18806880
TI  - Genetics of Meesmann corneal dystrophy: a novel mutation in the keratin 3 gene in
      an asymptomatic family suggests genotype-phenotype correlation.
AB  - PURPOSE: Juvenile epithelial corneal dystrophy of Meesmann (MCD, OMIM 122100) is
      a dominantly inherited disorder characterized by fragility of the anterior
      corneal epithelium and intraepithelial microcyst formation. Although the disease
      is generally mild and affected individuals are often asymptomatic, some suffer
      from recurrent erosions leading to lacrimation, photophobia, and deterioration in
      visual acuity. MCD is caused by mutations in keratin 3 (KRT3) or keratin 12
      (KRT12) genes, which encode cornea-specific cytoskeletal proteins. Seventeen
      mutations in KRT12 and two in KRT3 have been described so far. The purpose of
      this study was to investigate the genetic background of MCD in a Polish family.
      METHODS: We report on a three-generation family with MCD. Epithelial lesions
      characteristic for MCD were visualized with slit-lamp examination and confirmed
      by in vivo confocal microscopy. Using genomic DNA as a template, all coding
      regions of KRT3 and KRT12 were amplified and sequenced. Presence of the mutation
      was verified with restriction endonuclease digestion. RESULTS: In the proband,
      direct sequencing of the polymerase chain reaction (PCR) product from amplified
      coding regions of KRT3 and KRT12 revealed a novel 1493A>T heterozygous missense
      mutation in exon 7 of KRT3, which predicts the substitution of glutamic acid for
      valine at codon 498 (E498V). Using PCR-Restriction Fragment Length Polymorphism
      (RFLP) analysis, the mutation was demonstrated to segregate with the disease
      (four affected members, three non-affected) and to be absent in 100 controls from
      the Polish population, indicating that it is not a common polymorphism.
      CONCLUSIONS: Location of the E498V mutation emphasizes the functional relevance
      of the highly conserved boundary motifs at the COOH-terminus of the alpha-helical
      rod domain in keratin 3 (K3).

PMID- 18806881
TI  - Identification of candidate regions for a novel Usher syndrome type II locus.
AB  - PURPOSE: Chronic diseases affecting the inner ear and the retina cause severe
      impairments to our communication systems. In more than half of the cases, Usher
      syndrome (USH) is the origin of these double defects. Patients with USH type II
      (USH2) have retinitis pigmentosa (RP) that develops during puberty, moderate to
      severe hearing impairment with downsloping pure-tone audiogram, and normal
      vestibular function. Four loci and three genes are known for USH2. In this study,
      we proposed to localize the gene responsible for USH2 in a consanguineous family
      of Tunisian origin. METHODS: Affected members underwent detailed ocular and
      audiologic characterization. One Tunisian family with USH2 and 45 healthy
      controls unrelated to the family were recruited. Two affected and six unaffected
      family members attended our study. DNA samples of eight family members were
      genotyped with polymorphic markers. Two-point and multipoint LOD scores were
      calculated using Genehunter software v2.1. Sequencing was used to investigate
      candidate genes. RESULTS: Haplotype analysis showed no significant linkage to any
      known USH gene or locus. A genome-wide screen, using microsatellite markers, was
      performed, allowing the identification of three homozygous regions in chromosomes
      2, 4, and 15. We further confirmed and refined these three regions using
      microsatellite and single-nucleotide polymorphisms. With recessive mode of
      inheritance, the highest multipoint LOD score of 1.765 was identified for the
      candidate regions on chromosomes 4 and 15. The chromosome 15 locus is large (55
      Mb), underscoring the limited number of meioses in the consanguineous pedigree.
      Moreover, the linked, homozygous chromosome 15q alleles, unlike those of the
      chromosome 2 and 4 loci, are infrequent in the local population. Thus, the data
      strongly suggest that the novel locus for USH2 is likely to reside on 15q.
      CONCLUSIONS: Our data provide a basis for the localization and the identification
      of a novel gene implicated in USH2, most likely localized on 15q.

PMID- 18806882
TI  - A decrease in retinal progenitor cells is associated with early features of
      diabetic retinopathy in a model that combines diabetes and hypertension.
AB  - PURPOSE: Hyperglycemia and hypertension contribute to the development of diabetic
      retinopathy, and this may involve alterations in the normal retinal cell cycle.
      In this work, we examined the influence of diabetes and hypertension on retinal
      cell replication in vivo and the relationship between these changes and several
      early markers of diabetic retinopathy. METHODS: Diabetes was induced with
      streptozotocin in 4- and 12-week-old spontaneously hypertensive rats (SHR) and
      their Wistar Kyoto (WKY) controls. The rats were killed 15 days later. Retinal
      cells stained with bromodeoxyuridine (BrdU) were seen in rats of both ages.
      RESULTS: In 12-week-old rats, the number of BrdU-positive retinal cells was
      higher in SHR than in WKY rats. After 15 days of diabetes mellitus, there was a
      marked reduction in cell replication only in diabetic SHR (p=0.007). The BrdU
      positive cells expressed neural, glial, or vascular progenitor markers. There was
      greater expression of p27(Kip1) in the ganglion cell layer of both diabetic
      groups (p=0.05), whereas in the inner nuclear layer there was enhanced expression
      only in diabetic SHR (p=0.02). There was a marked increase in the retinal
      expression of fibronectin (p=0.04) and vascular endothelial growth factor
      (p=0.02) in diabetic SHR that was accompanied by blood-retinal barrier breakdown
      (p=0.01). DISCUSSION: Concomitant diabetes and hypertension attenuated the
      proliferation of retinal cells, and it is associated with an increase in
      p27(Kip1) expression, fibronectin accumulation, and blood-retinal barrier
      breakdown. The replicative retinal cells displayed characteristics of progenitor
      cells.

PMID- 18806883
TI  - Lipoprotein(a), homocysteine, and retinal arteriosclerosis.
AB  - PURPOSE: Elevated levels of lipoprotein(a) [Lp(a)] and homocysteine (Hcy) have
      been implicated as risk factors for vascular diseases. The study was performed to
      explore the possible relationship between retinal arteriosclerosis and serum
      Lp(a) and Hcy levels. METHODS: Study subjects consisted of 80 nonsmoking male
      patients with retinal arteriosclerosis and 54 healthy nonsmoker males as
      controls. Retinal arteriosclerosis was graded according to the Scheie
      classification. Serum levels of lipids, lipoproteins, Lp(a), and Hcy were
      measured by standard methods. RESULTS: The serum level of Hcy was higher in
      patients (24.2+/-8.1 micromol/l) than controls (10.5+/-4.1 micromol/l); p<0.01.
      Serum levels of Lp(a) in patients (47.9+/-33.1 mg/dl) was also higher than
      controls (11.7+/-7.6 mg/dl); p<0.01. There was a significant direct linear
      correlation between the degree of retinal arteriosclerosis and Lp(a) level
      (r=0.61, p<0.01), the degree of retinal arteriosclerosis and Hcy level (r=0.72,
      p<0.01), and also between Lp(a) and Hcy levels (r=0.67, p<0.01). CONCLUSIONS: The
      association between retinal arteriosclerosis and serum Lp(a) and Hcy levels
      suggests that Lp(a) as well as Hcy could play a role in the development of
      retinal arteriosclerosis.

PMID- 18806884
TI  - EDN1 Lys198Asn is associated with diabetic retinopathy in type 2 diabetes.
AB  - PURPOSE: We tested the hypothesis that genetic variants in vasoactive and
      angiogenic factors regulating the retina vasculature contribute to the
      development of diabetic retinopathy (DR). METHODS: A case-control study was
      performed to study the genetic association between DR and polymorphic variants of
      EDN1 (Lys198Asn), LTA (IVS1-80C>A, IVS1-206G>C, IVS1-252A>G), eNOS (Glu298Asp),
      and ITGA2 (BgI II) in a Chinese population with type 2 diabetes mellitus. A well
      defined population with type 2 diabetes, consisting of 127 controls and 216 DR
      patients, was recruited. RESULTS: A higher frequency of the Asn/Asn genotype of
      EDN1 was found in individuals with at least 10 years of diabetes and no
      retinopathy (controls) compared with DR patients with any duration of diabetes
      (DR: 2.3%; control: 11.0%; p=0.0002). The Asn allele was also more frequent in
      controls than DR patients (DR: 16.4%; control: 29.5%; p=0.007). Multiple logistic
      regression analysis showed that the Asn/Asn genotype was the factor most
      significantly associated with reduced risk of DR (odds ratio=0.19; 95% CI: 0.07
      0.53; p=0.002) and with late onset of diabetes (Asn/Asn: 59 years; Lys/Lys +
      Lys/Asn: 53 years; p=0.02). Moreover, the Lys/Lys genotype was more common among
      patients with nonproliferative (75.7%) than proliferative DR (56.9%; p=0.008).
      The distributions of Lys198Asn alleles in hypertension did not differ from
      normotensive subjects. No associations between DR and polymorphisms of LTA, eNOS,
      or ITGA2 were detected, and there were no detectable gene-gene or gene
      environmental interactions among the polymorphisms. CONCLUSIONS: The Asn/Asn
      genotype of EDN1 was associated with a reduced risk of DR and with delayed onset
      of type 2 diabetes.

PMID- 18806885
TI  - Genetic analysis of the clusterin gene in pseudoexfoliation syndrome.
AB  - PURPOSE: Pseudoexfoliation syndrome is a major risk factor for the development of
      glaucoma. Following recent reports of a strong association of coding variants in
      the lysyl oxidase-like 1 (LOXL1) gene with this syndrome but low penetrance and
      variable disease frequency between different populations, we aimed to identify
      additional genetic factors contributing to the disease. The clusterin (CLU) gene
      has been proposed as a candidate because of the presence of clusterin protein in
      pseudoexfoliation deposits, its varied levels in aqueous humor of cases compared
      to controls, and the role of the protein as a molecular chaperone. We
      investigated the association of genetic variants across CLU in pseudoexfoliation
      syndrome and analyzed molecular characteristics of the encoded protein in ocular
      tissues. METHODS: The expression of clusterin in relevant ocular tissues was
      assessed using western blotting. Nine tag single nucleotide polymorphisms (SNPs)
      across CLU were genotyped in 86 cases of pseudoexfoliation syndrome and 2422
      controls from the Australian Blue Mountains Eye Study cohort. Each SNP and
      haplotype was assessed for association with the syndrome. RESULTS: Clusterin was
      identified in normal human iris, the ciliary body, lens capsule, optic nerve, and
      aqueous humor. Post-translational modification gives rise to a 100 kDa precursor
      protein in ocular tissues, larger than that reported in non-ocular tissues. One
      CLU SNP (rs3087554) was nominally associated with pseudoexfoliation syndrome at
      the genotypic level (p=0.044), although not when the age of controls was
      restricted to those over 73 years. Only age and the LOXL1 diplotype were
      significant factors in the logistic regression. One haplotype of all nine CLU
      SNPs was also associated (p=0.005), but the significance decreased slightly with
      the use of the age-restricted controls (p=0.011). CONCLUSIONS: Clusterin is
      present in ocular anterior segment tissues involved in pseudoexfoliation
      syndrome. Although one haplotype may contribute in a minor way to genetic risk of
      pseudoexfoliation syndrome, common variation in this gene is not a major
      contributor to the risk of pseudoexfoliation syndrome.

PMID- 18806887
TI  - Electrophilic Activation of Lewis Base Complexes of Borane with Trityl
      Tetrakis(pentafluorophenyl)borate.

PMID- 18806886
TI  - Cannabis and endocannabinoid modulators: Therapeutic promises and challenges.
AB  - The discovery that botanical cannabinoids such as delta-9 tetrahydrocannabinol
      exert some of their effect through binding specific cannabinoid receptor sites
      has led to the discovery of an endocannabinoid signaling system, which in turn
      has spurred research into the mechanisms of action and addiction potential of
      cannabis on the one hand, while opening the possibility of developing novel
      therapeutic agents on the other. This paper reviews current understanding of CB1,
      CB2, and other possible cannabinoid receptors, their arachidonic acid derived
      ligands (e.g. anandamide; 2 arachidonoyl glycerol), and their possible
      physiological roles. CB1 is heavily represented in the central nervous system,
      but is found in other tissues as well; CB2 tends to be localized to immune cells.
      Activation of the endocannabinoid system can result in enhanced or dampened
      activity in various neural circuits depending on their own state of activation.
      This suggests that one function of the endocannabinoid system may be to maintain
      steady state. The therapeutic action of botanical cannabis or of synthetic
      molecules that are agonists, antagonists, or which may otherwise modify
      endocannabinoid metabolism and activity indicates they may have promise as
      neuroprotectants, and may be of value in the treatment of certain types of pain,
      epilepsy, spasticity, eating disorders, inflammation, and possibly blood pressure
      control.

PMID- 18806888
TI  - Nanobiosensors: optofluidic, electrical and mechanical approaches to biomolecular
      detection at the nanoscale.
AB  - Next generation biosensor platforms will require significant improvements in
      sensitivity, specificity and parallelity in order to meet the future needs of a
      variety of fields ranging from in vitro medical diagnostics, pharmaceutical
      discovery and pathogen detection. Nano-biosensors, which exploit some fundamental
      nanoscopic effect in order to detect a specific biomolecular interaction, have
      now been developed to a point where it is possible to determine in what cases
      their inherent advantages over traditional techniques (such as nucleic acid
      microarrays) more than offset the added complexity and cost involved constructing
      and assembling the devices. In this paper we will review the state of the art in
      nanoscale biosensor technologies, focusing primarily on optofluidic type devices
      but also covering those which exploit fundamental mechanical and electrical
      transduction mechanisms. A detailed overview of next generation requirements is
      presented yielding a series of metrics (namely limit of detection,
      multiplexibility, measurement limitations, and ease of fabrication/assembly)
      against which the various technologies are evaluated. Concluding remarks
      regarding the likely technological impact of some of the promising technologies
      are also provided.

PMID- 18806890
TI  - Characterization of a novel transcript variant of human STAU1 gene.
AB  - Human STAU1 is one member of the family of double-stranded RNA (dsRNA)-binding
      proteins. It is thought to function in transporting mRNA, controlling translation
      and eliciting mRNA decay in neurons, and to function in infection of influenza
      virus and human immunodeficiency virus type 1 (HIV-1). Four transcripts coding
      two isoforms have been identified before. In this study, we have isolated a novel
      transcript of STAU1, coding a novel isoform that has six amino acids more
      (SFPLKQ) than isoform a. In order to examine the tissue distribution of this
      novel isoform, we have performed RT-PCR experiments and the analysis showed that
      it was highly expressed in heart, liver, kidney and pancreas.

PMID- 18806889
TI  - Autophagy in neuroprotection and neurodegeneration: A question of balance.
AB  - A central issue in developing therapies for neurodegenerative diseases involves
      understanding why adaptive responses to stress or injury fail to prevent synaptic
      dysfunction and neuronal cell death. Macroautophagy is a major, evolutionarily
      conserved response to nutrient and bioenergetic stresses, which has the capacity
      to remove aggregated proteins and damaged organelles such as mitochondria. This
      has prompted intense interest in autophagy-related therapies for Huntington's,
      Alzheimer's, Parkinson's, stroke and other neurological diseases. However,
      excessive or imbalanced induction of autophagic recycling can actively contribute
      to neuronal atrophy, neurite degeneration and cell death. Oxidative-, aging- and
      disease-related increase in demand for autophagy, coupled with declining axonal
      trafficking, lysosomal degradation or biosynthetic efficiencies promote increased
      susceptibility to a harmful state of autophagic stress. A more complete
      understanding of dysfunction along the entire spectrum of autophagic recycling,
      from autophagosome formation through clearance and regeneration of new cellular
      components is necessary to restore balance to the system, promote neuronal health
      and maximize therapeutic potentials.

PMID- 18806891
TI  - Differential in vitro inhibitory effects of anticancer drugs on tumor-associated
      carbonic anhydrase isozymes CA IX and CA XII.
AB  - Carbonic anhydrase IX (CA IX) and, to a lesser extent, carbonic anhydrase XII (CA
      XII) are highly overexpressed in hypoxic tumors. In this study, the inhibitory
      effects of 11 different anticancer drugs including paclitaxel, amethopterin,
      etoposide, irinotecan, gemcitabine, 5-fluorouracil, oxaliplatin, epirubicin,
      cisplatin and carboplatin on the tumor-associated carbonic anhydrase isozymes CA
      IX and CA XII and cytosolic carbonic anhydrases I and II have been investigated.
      SX.18MV-R Applied Photophysics stopped-flow instrument was used for measuring the
      initial velocities for the CO2 hydration reaction catalyzed by different CA
      isozymes, by following the change in the absorbance of a pH indicator. CA IX and
      CA XII were the most affected by carboplatin and cisplatin amongst the panel of
      anticancer drugs. Moreover, the cytosolic carbonic anhydrases I and II can also
      be affected. Consequently, CA IX and CA XII are interesting targets for
      anticancer drug development, although more selective and powerful CA inhibitors
      could prove useful for elucidating the role of the protein in hypoxic cancers,
      for controlling the pH imbalance in tumor cells and for developing diagnostic or
      therapeutic applications for the management of hypoxic tumors, generally
      unresponsive to classical chemo- and radiotherapy.

PMID- 18806892
TI  - Estonian and Russian Federation amoxicillin formulations: a comparative study of
      in vitro dissolution.
AB  - The in vitro dissolution properties were compared for four different formulations
      from the Estonian drug market and four from the Russian Federation drug market.
      Seven of the eight formulations tested released at least 75% or 80% amoxicillin
      during 30- or 90-min dissolution tests (37 degrees C, purified water, 75 rpm),
      respectively. One marketed Russian Federation formulation released 74%
      amoxicillin over a 90-min period. The present study shows that, in general, the
      in vitro dissolution properties of the Russian Federation amoxicillin
      formulations are, with some minor exceptions, comparable to those of the Estonian
      formulations.

PMID- 18806893
TI  - Proteomic detection of changes in protein expression induced by cordycepin in
      human hepatocellular carcinoma BEL-7402 cells.
AB  - The nucleoside analogue cordycepin (3 '-deoxyadenosine, 3 '-dA), one of the
      components of Cordyceps militaris, has been shown to inhibit the growth of
      various tumor cells. However, the probable mechanism is still obscure. In this
      study, the inhibition of cell growth and changes in protein expression induced by
      cordycepin were investigated in BEL-7402 cells. Using the MTT assay and flow
      cytometry, we found that cordycepin inhibits cell viability and induces apoptosis
      in BEL-7402 cells. Additionally, the proteins were separated using two
      dimensional polyacrylamide gel electrophoresis, and eight proteins were found to
      be significantly affected by cordycepin compared to untreated control; among
      them, two were downregulated and six were upregulated. Of the eight proteins, six
      were identified with peptide mass fingerprinting using matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) after in
      gel trypsin digestion. These proteins are involved in various aspects of cellular
      metabolism. It is suggested that the effect of cordycepin on the growth of tumor
      cells is significantly related to the metabolism-associated protein expression
      induced by cordycepin.

PMID- 18806894
TI  - Antinociceptive, antiinflammatory and antipyretic properties of Channa striatus
      fillet aqueous and lipid-based extracts in rats.
AB  - The present study was carried out to elucidate the antinociceptive,
      antiinflammatory and antipyretic properties of the aqueous and lipid-based
      extracts of Channa striatus fillet in rats. The antinociceptive activity was
      assessed using the formalin test, and the antiinflammatory and antipyretic
      activities were assessed using the carrageenan-induced paw edema and brewer's
      yeast-induced pyrexia tests, respectively. Both types of extracts were prepared
      in concentrations of 10%, 50% and 100% by serial dilution in distilled water or
      dimethyl sulfoxide, respectively, and were administered subcutaneously 30 min
      prior to each test. Except for the 10% aqueous extract which exhibits activity
      only in the early phase, the extracts were found to exhibit significant (P <
      0.05) activity in the early and late phases of the formalin test. Furthermore,
      the aqueous and lipid-based extracts were also found to show significant (P <
      0.05) antiinflammatory activity, with the former showing a greater effect at the
      lowest concentration used. The lipidbased, but not the aqueous, extract was found
      to have significant (P < 0.05) activity in the pyrexia test. In conclusion, the
      present study demonstrated that C. striatus extracts possess antinociceptive,
      antiinflammatory and antipyretic activities.

PMID- 18806895
TI  - Inhibitory effect of nicorandil on the contraction of isolated human urinary
      bladder detrusor muscle.
AB  - This study was performed to determine whether the antianginal drug nicorandil
      relaxes isolated human detrusor muscle. Ten strips of detrusor muscle obtained
      from 10 pediatric patients who underwent surgery on the urinary bladder were
      contracted with 80 mM potassium chloride (KCl) before and after incubation with
      four concentrations of nicorandil (100, 200, 400 and 800 microM). The percent
      inhibition by nicorandil of the height and area under the curve (AUC) of KCl
      induced contractions of the detrusor strips was calculated. The effect of
      glibenclamide (10 microM) on nicorandil (800 microM)-induced inhibition of KCl
      induced detrusor contractions was also studied. Nicorandil caused a concentration
      dependent inhibition of KCl-induced contractions of the detrusor strips. The
      percent inhibition of the height of KCl-induced contractions of the detrusor by
      nicorandil was significant at concentrations of 200, 400 and 800 microM. The
      percent inhibition of the AUC for KCl-induced detrusor contractions was
      significant at all four concentrations of nicorandil used. Glibenclamide reversed
      the inhibitory effect of 800 microM nicorandil on KCl-induced detrusor
      contractions. These results suggest that nicorandil inhibits KCl-induced
      contractions of isolated human detrusor muscle and may therefore be useful in
      clinical conditions requiring detrusor muscle relaxation.

PMID- 18806896
TI  - Coenzyme Q(10) and alpha-lipoic acid supplementation in diabetic rats: conduction
      velocity distributions.
AB  - Diabetic neuropathies are a family of nerve disorders caused by diabetes.
      Patients with diabetes can develop nerve problems at any time, but the longer a
      person has diabetes the greater the risk. This study aims to investigate diabetes
      and coenzyme Q(10) (CoQ(10)) or alpha-lipoic acid (ALA) supplementation-induced
      changes in the conduction velocity (CV) distributions of rat sciatic nerve
      fibers. Sciatic nerve compound action potentials (CAPs) were recorded by suction
      electrode and CV distributions by the collision technique. Diabetes resulted in a
      significant increase in time to peak, rheobase and chronaxie values of these CAP
      waveforms, whereas the maximum depolarization, area, kinetics and CVs of both
      fast and slow nerve fiber groups were found to be decreased. Coenzyme Q(10)
      (CoQ(10)) supplementation was found to have some positive effect on the diabetes
      induced alterations. CoQ(10) supplementation induced positive changes mainly in
      the area and fall-down phase of the kinetics of CAP waveforms, as well as
      rheobase, chronaxie and speed of the intermediately conducting groups (
      approximately or equal to 40 m/s). alpha-Lipoic acid (ALA) supplementation did
      not produce statistically significant effects. This study has shown for the first
      time that diabetes induces a shift of actively contributing nerve fibers toward
      slower CVs, and supplementation with CoQ(10) not only stopped this shift but also
      tended to restore velocities toward those of the age-matched control group. In
      addition to its effects on mitochondrial alterations, these positive effects of
      CoQ10 on diabetic neuropathy can be attributed to its antioxidant activity.

PMID- 18806897
TI  - Cardiovascular effect of Artemisia herba alba aqueous extract in spontaneously
      hypertensive rats.
AB  - This study aimed to evaluate the hypotensive activity of Artemisia herba alba
      aqueous extract (AHAE) in spontaneously hypertensive rats (SHR). AHAE was
      lyophilized and administered daily at a dose of 150 mg/kg for 20 days. AHAE
      administration produced a significant reduction in systolic blood pressure after
      8 days of oral administration (P < 0.01), and a sustained reduction was observed
      at the end of treatment (P < 0.01). Heart rate remained unchanged during the 20
      days of oral AHAE administration. In addition, AHAE administration produced a
      significant increase in urinary output (P < 0.01) and glomerular filtration rate
      (P < 0.01) on day 8 of treatment. Urinary electrolyte excretion was also modified
      during the 20 days of AHAE administration, and a significant increase in urinary
      sodium and potassium excretion was observed from day 4 (P < 0.01) to day 20 (P <
      0.001). However, urinary chloride excretion was increased from day 8 (P < 0.01)
      to the end of treatment (P < 0.001). The hypotensive effect appeared to be
      independent of the renin-angiotensin system since AHAE did not affect plasma
      angiotensin-converting enzyme or renin activities (P > 0.05) after 20 days of
      oral administration. We conclude that AHAE possesses antihypertensive activity in
      SHR and that the underlying mechanism appears to involve, at least in part, an
      increase in urine and electrolyte output.

PMID- 18806898
TI  - Gateways to clinical trials.
AB  - (+)-Dapoxetine hydrochloride, (R)-Etodolac; Abatacept, ABT-510, Adalimumab,
      Agatolimod sodium, Alemtuzumab, Alvocidib hydrochloride, Aminolevulinic acid
      methyl ester, Aripiprazole, AS01B, AS02B, AS02V, Azacitidine; Becatecarin,
      Bevacizumab, Bevirimat, Bortezomib, Bremelanotide; CAIV-T, Canfosfamide
      hydrochloride, CHR-2797, Ciclesonide, Clevidipine; Darbepoetin alfa, Decitabine,
      Degarelix acetate, Dendritic cell-based vaccine, Denosumab, Desloratadine, DMXB
      Anabaseine, Duloxetine hydrochloride, Dutasteride; Ecogramostim, Eicosapentaenoic
      acid/docosahexaenoic acid, Eletriptan, Enzastaurin hydrochloride, Erlotinib
      hydrochloride, Escitalopram oxalate, Etoricoxib, Everolimus, Ezetimibe,
      Ezetimibe/simvastatin; Ferumoxytol, Fesoterodine fumarate, Fulvestrant;
      Gefitinib, GM-CSF DNA, GSK-690693; H5N1 avian flu vaccine, Hepatitis B
      hyperimmunoglobulin, Human Fibroblast Growth Factor 1, Hypericin-PVP; Icatibant
      acetate, Iclaprim, Immunoglobulin intravenous (human), Ipilimumab, ISS-1018; L19
      IL-2, Lapuleucel-T, Laropiprant, Liposomal doxorubicin, LP-261, Lumiracoxib, LY
      518674; MDV-3100, MGCD-0103, Mirabegron, MyoCell; NASHA/Dx, Niacin/laropiprant;
      O6-Benzylguanine, Ocrelizumab, Olmesartan medoxomil, Omalizumab; P-276-00,
      Paclitaxel nanoparticles, Paclitaxel nanoparticles, Padoporfin, Paliperidone, PAN
      811, Pegaptanib octasodium, Pegfilgrastim, Pemetrexed disodium, PF-00299804,
      Pimecrolimus, Prasugrel, Pregabalin; Reolysin, Rimonabant, Rivaroxaban,
      Rosuvastatin calcium; Satraplatin, SCH-697243,Selenite sodium, Silodosin,
      Sorafenib, Sunitinib malate; Talarozole, Taxus, Temsirolimus, Tocilizumab,
      Tolevamer potassium sodium, Tremelimumab, TTP-889; Uracil; V-260,
      Valsartan/amlodipine besylate, Vardenafil hydrochloride hydrate, Varenicline
      tartrate, Varespladib, Vitespen, Voclosporin, VX-001; Xience V; Zotarolimus
      eluting stent.

PMID- 18806899
TI  - Desvenlafaxine succinate for major depressive disorder.
AB  - Desvenlafaxine (O-desmethylvenlafaxine) is the major active metabolite of
      venlafaxine. Desvenlafaxine succinate is now undergoing active evaluation for its
      therapeutic efficacy in a variety of disorders, including major depressive
      disorder, vasomotor symptoms associated with menopause, fibromyalgia and diabetic
      neuropathy. Desvenlafaxine is a serotonin and norepinephrine reuptake inhibitor
      (SNRI) with similar activity to its parent compound venlafaxine, and little
      affinity for other brain targets, including muscarinic, cholinergic, histamine
      H(1) and alpha-adrenergic receptors. Desvenlafaxine has linear pharmacokinetics,
      low protein binding, a half-life of approximately 10 hours and is metabolized
      primarily via glucuronidation, and to a minor extent through CYP3A4. The
      desvenlafaxine succinate formulation appears to have good oral bioavailability.
      Clearance rates are reduced in the elderly, those with severe renal dysfunction
      and those with moderate to severe hepatic dysfunction, which may require dosage
      adjustments. Three published clinical trials have shown supportive but mixed
      results for the efficacy of desvenlafaxine in the treatment of major depressive
      disorder with daily doses ranging from 100 mg to 400 mg. One published clinical
      trial has shown mixed results for the efficacy of desvenlafaxine in the treatment
      of vasomotor symptoms associated with menopause with daily doses ranging from 50
      mg to 200 mg. In these four clinical trials, desvenlafaxine was associated with
      several mild adverse effects, with the most common effect being nausea. Less
      common, but more serious, adverse effects reported in these trials included
      hypertension, QTc interval prolongation, exacerbation of ischemic cardiac
      disease, elevated lipids and elevated liver enzymes. The exact nature of these
      serious adverse effects, including the prevalence, clinical significance and
      potential risk factors, still needs to be fully elucidated. Desvenlafaxine has a
      low propensity for pharmacokinetic-based drug interactions, although it has the
      same potential for pharmacodynamic interactions as other serotonin-norepinephrine
      reuptake inhibitors. Desvenlafaxine is currently another treatment option for
      major depressive disorder. The only identified potential advantage of
      desvenlafaxine over venlafaxine or other antidepressant agents at this time is
      the apparently reduced risk for pharmacokinetic drug interactions.

PMID- 18806900
TI  - Sitafloxacin hydrate for bacterial infections.
AB  - Sitafloxacin hydrate (DU-6859a, Gracevit), a new-generation, broad-spectrum oral
      fluoroquinolone that is very active against many Gram-positive, Gram-negative and
      anaerobic clinical isolates, including strains resistant to other
      fluoroquinolones, was recently approved in Japan for the treatment of respiratory
      and urinary tract infections. Sitafloxacin is active against methicillin
      resistant staphylococci, Streptococcus pneumoniae and other streptococci with
      reduced susceptibility to levofloxacin and other quinolones and enterococci.
      Sitafloxacin has also demonstrated activity against clinical isolates of
      Klebsiella pneumoniae (including about 67% of strains producing extended
      spectrum, beta-lactamases and resistant to ciprofloxacin), Enterobacter cloacae,
      Pseudomonas aeruginosa with some activity against quinolone-resistant strains and
      Acinetobacter baumannii. The in vitro activity against anaerobes is comparable to
      imipenem or metronidazole. In a published phase II randomized, open-label,
      multicenter study of patients hospitalized with pneumonia, sitafloxacin (400 mg
      once daily) was comparable to imipenem/cilastatin (500 mg three times a day).
      Results of the phase III trials of sitafloxacin are not available in English. The
      clinical safety profile of sitafloxacin has been characterized from 1,059
      patients who participated in 10 clinical trials. The most common events with 50
      or 100 mg twice daily were gastrointestinal disorders (17.2%), mostly diarrhea,
      and abnormal laboratory test results (16.2%), mostly liver enzyme elevations. For
      Japanese patients, sitafloxacin provides the broad-spectrum coverage promised by
      clinafloxacin and trovafloxacin and comparable to carbapenems. While it is
      currently limited by its potential for phototoxicity in Caucasians, phototoxicity
      is essentially irrelevant if sitafloxacin is used in hospitals and especially in
      intensive care units.

PMID- 18806901
TI  - Diastolic dysfunction: a link between hypertension and heart failure.
AB  - Diastolic heart failure is characterized by the symptoms and signs of heart
      failure, a preserved ejection fraction and abnormal left ventricular (LV)
      diastolic function caused by a decreased LV compliance and relaxation. The signs
      and symptoms of diastolic heart failure are indistinguishable from those of heart
      failure related to systolic dysfunction; therefore, the diagnosis of diastolic
      heart failure is often one of exclusion. The majority of patients with heart
      failure and preserved ejection fraction have a history of hypertension.
      Hypertension induces a compensatory thickening of the ventricular wall in an
      attempt to normalize wall stress, which results in LV concentric hypertrophy,
      which in turn decreases LV compliance and LV diastolic filling. There is an
      abnormal accumulation of fibrillar collagen accompanying the hypertension-induced
      LV hypertrophy, which is also associated with decreased compliance and LV
      diastolic dysfunction. There are no specific guidelines for treating diastolic
      heart failure, but pharmacological treatment should be directed at normalizing
      blood pressure, promoting regression of LV hypertrophy, preventing tachycardia
      and treating symptoms of congestion. Preventive strategies directed toward an
      early and aggressive blood pressure control are likely to offer the greatest
      promise for reducing the incidence of diastolic heart failure.

PMID- 18806902
TI  - Antifungal prophylaxis in adult hematopoietic stem cell transplant recipients.
AB  - Invasive fungal infections (IFIs) are a frequent, costly and potentially life
      threatening complication in hematopoietic stem cell transplant (HSCT) recipients.
      Most prevalent among the causative pathogens are Candida spp. and Aspergillus
      spp. Risk factors that further increase the risk of IFIs in this patient
      population include allogeneic transplant and acute graft versus host disease.
      Among strategies to improve outcomes is the administration of antifungal
      prophylaxis. However, optimal administration requires the identification of
      patients who are at the highest risk of developing a fungal infection, thus
      restricting concerns of drug cost, toxicity and resistance to those most likely
      to benefit. Currently, there are several antifungal agents recommended by the
      National Comprehensive Cancer Network for the prophylaxis of IFIs. These include
      fluconazole, itraconazole, voriconazole, posaconazole and micafungin. Fluconazole
      was widely considered the standard agent for prophylaxis in patients at lower
      risk of mold infections. New data support the efficacy of the newer triazole
      posaconazole and the echinocandin micafungin in this patient population..

PMID- 18806903
TI  - New frontiers in the pharmacological management of Parkinson's disease.
AB  - Rasagiline, a selective COMT inhibitor, and rotigotine, a transdermal dopamine
      (D2) agonist, are two new agents that have been approved in the U.S. and Europe
      for the treatment of Parkinson's disease. Rasagiline is approved in the U.S. for
      both monotherapy and as an adjunct to levodopa. Its role in preventing disease
      progression has yet to be proven, but a large-scale study (ADAGIO) is under way.
      Rotigotine is approved for early-stage disease in Europe and the U.S. but is only
      approved in Europe for late-stage disease. It has recently been recalled due to
      the formation of insoluble crystals that interfere with absorption and may reduce
      its efficacy. Measures are being taken by the manufacturer to solve this problem.
      Istradefylline, and adenosine receptor antagonist, showed early promise but
      efficacy has not been demonstrated consistently, possibly due to higher than
      expected placebo effect. This has resulted in a nonapprovable letter from the
      FDA. With regard to perampanel, additional studies are needed to demonstrate
      safety and efficacy. Sanifamide and pardoprunox are agents that target multiple
      receptors that may modulate dyskinesia and other nonmotor symptoms in addition to
      motor symptoms, but phase III data are not yet available. Lusuride is an older
      dopamine agonist that has been reformulated as a transdermal patch and as a
      subcutaneous injection and may offer advantages in refractory patients with motor
      fluctuations. Sphermaine is a novel cell therapy designed to provide a localized
      source of levodopa directly to the brain. Gene therapies including AAV-GAD, AAV
      AADC and AAV2-neurturin are in early stages of development in patients with
      advanced-stage disease but early safety data are promising.

PMID- 18806904
TI  - Clobetasol propionate--where, when, why?
AB  - Clobetasol propionate is the most potent of all topical steroids. It is
      successfully applied in the treatment of various skin diseases such as atopic
      dermatitis, psoriasis and vulvar lichen sclerosus. The therapy is, however,
      mainly symptomatic. A preventive effect is only reported in the treatment of the
      latter. Clobetasol propionate exerts antiinflammatory, immunosuppressive and
      antimitotic effects influencing the growth, differentiation and function of
      various cells and inhibiting cytokine production. Seven different dosage forms
      are available to deliver the drug to the living cells of the skin. Their choice
      might additionally affect patient compliance. The potency of clobetasol
      propionate, however, is accompanied by local and systemic side effects, such as
      skin atrophy and hypothalamic-pituitary-adrenal axis suppression. Patients
      applying clobetasol propionate must be well instructed in how to use it.
      Physicians prescribing clobetasol propionate should consider a diversity of
      factors and be able to answer the questions where, when and why.

PMID- 18806905
TI  - Botulinum toxin products overview.
AB  - The tremendous success of botulinum toxin type A (BOTOX(R), Allergan Inc.) in the
      cosmetic arena has acted as a stimulus for the development of other neurotoxins.
      After more than 2 decades of use, BOTOX(R) has become synonymous with wrinkle
      reduction and is considered to be the one of the most common non-surgical
      cosmetic procedures performed worldwide. Because of its vast popularity among
      patients seeking non-invasive methods to achieve facial rejuvenation, physicians
      from diverse specialties have integrated botulinum toxin injections into their
      existing practices. Herein, we present an overview of botulinum toxin products
      for cosmetic applications that have received regulatory approval or are under
      development.

PMID- 18806906
TI  - Update on sunscreens.
AB  - Sunscreens have been around for more than 70 years. Designed originally to
      protect against sunburn, recognition of the various harmful effects of
      ultraviolet (UV) radiation has broadened the use of sunscreens. The addition of
      effective UVA sunscreen agents has enabled claims beyond protection against
      sunburn to include prevention of idiopathic photodermatosis, actinic keratoses,
      skin cancer, and photoaging. This article will review some of the recent advances
      in photoprotection, including the development of sunscreen formulations offering
      higher and broader protection against solar radiation.

PMID- 18806907
TI  - Heavy metals in the surface sediments in Lanzhou Reach of Yellow River, China.
AB  - The heavy metal pollution and their fractionations in the surface sediments of
      Yellow River in Lanzhou Reach was monitored for arsenic (As), lead (Pb), Zinc
      (Zn), chromium (Cr), copper (Cu) and manganese (Mn) with Inductively Coupled
      Plasma-Atomic Emission Spectrometry (ICP-AES). The mean sediment concentrations
      (in microg/g dry weight) ranged from 13.68-48.11 (As), 26.39-77.66 (Pb), 89.80
      201.88 (Zn), 41.49-128.30 (Cr), 29.72-102.22 (Cu), and 773.23-1459.69 (Mn).
      Spatial distribution showed that each heavy metal concentration remained almost
      constant in this reach. Correlation coefficients indicated that metals were not
      strongly associated with sediment sand content or organic carbon content (f(oc)).
      Labile fractions (exchangeable + carbonate + Fe-Mn oxide) had no significant
      correlations with sand content or f(oc), either. Results from the present study
      are useful for understanding heavy metal distributions in a torrential river
      sediment environment.

PMID- 18806908
TI  - Measurements and characteristics of nitrogen-containing compounds in atmospheric
      particulate matter in Beijing, China.
AB  - The total nitrogen (TN) and water-soluble nitrogenous ions were determined by
      using CHN Elemental Analyzer and ion chromatography method, respectively, from
      November 24, 1998 to February 12, 1999 in Beijing. The average concentrations of
      TN, NH(4) (+) and NO(3) (-) were 10.62 microg N m(-3), 6.67 microg m(-3) and
      10.01 microg m(-3), respectively. The total inorganic nitrogen (IN) calculated
      from NH(4) (+) and NO(3) (-) was 7.45 microg N m(-3), accounting for 70% of TN,
      i.e., 30% of TN existed as organic nitrogen form (ON). The correlation between ON
      and other pollution tracers showed that, coal combustion, biomass burning, soil
      humic matter and secondary formation were the important sources of ON in
      particulate matter in Beijing.

PMID- 18806909
TI  - Persistent organochlorine pesticide residues in tissues and eggs of white-backed
      vulture, Gyps bengalensis from different locations in India.
AB  - Organochlorine pesticide residues were determined in tissues of five Indian white
      backed vultures and two of their eggs collected from different locations in
      India. All the samples had varying levels of residues. p,p'-DDE ranged between
      0.002 microg/g in muscle of vulture from Mudumali and 7.30 microg/g in liver of
      vulture from Delhi. Relatively higher levels of p,p'-DDT and its metabolites were
      documented in the bird from Delhi than other places. Dieldrin was 0.003 and 0.015
      microg/g while p,p'-DDE was 2.46 and 3.26 microg/g in egg one and two
      respectively. Dieldrin appeared to be lower than the threshold level of 0.5
      microg/g. p,p'-DDE exceeded the levels reported to have created toxic effects in
      eggs of other wild birds. Although varying levels of DDT, HCH, dieldrin,
      heptachlor epoxide and endosulfan residues were detected in the vulture tissues,
      they do not appear to be responsible for the present status of population in
      India.

PMID- 18806910
TI  - A randomized controlled trial of pelvic floor muscle training for stages I and II
      pelvic organ prolapse.
AB  - Forty-seven women participated in a pilot study for a multi-centre randomized
      controlled trial of the effectiveness of pelvic floor muscle training (PFMT) for
      women with prolapse. Women with symptomatic stage I or II prolapse [measured by
      Pelvic Organ Prolapse Quantification (POP-Q)] were randomized to a 16-week
      physiotherapy intervention (PFMT and lifestyle advice; n = 23) or a control group
      receiving a lifestyle advice sheet (n = 24). Symptom severity and quality of life
      were measured via postal questionnaires. Blinded POP-Q was performed at baseline
      and follow-up. Intervention women had significantly greater improvement than
      controls in prolapse symptoms (mean score decrease 3.5 versus 0.1, p = 0.021),
      were significantly more likely to have an improved prolapse stage (45% versus 0%,
      p = 0.038) and were significantly more likely to say their prolapse was better
      (63% versus 24%, p = 0.012). The data support the feasibility of a substantive
      trial of PFMT for prolapse. A multi-centre trial is underway.

PMID- 18806911
TI  - Management of complications arising from transvaginal mesh kit procedures: a
      tertiary referral center's experience.
AB  - This case series' purpose is to review a referral center's experience with
      complications from mesh kits. A chart review of 12 patients who presented with
      complications associated with transvaginal mesh kit procedures was performed. All
      patients underwent complete surgical removal of the mesh to treat mesh exposure,
      pain, or vaginal bleeding/discharge followed by an anterior or posterior repair.
      The mean follow-up time after surgery was 3.4 months. Eight of 12 patients had
      mesh that had formed a fibrotic band. Six of 12 patients had complete resolution
      of pain. Of the nine patients with mesh exposure, all required significant
      resection of the vaginal wall. No further mesh exposure occurred. The use of
      transvaginal mesh kits may cause previously undescribed complications such as
      pelvic/vaginal pain or large extrusions requiring complete removal. Removal of
      all mesh except the arms may cure or significantly improve these problems.

PMID- 18806912
TI  - Constriction of the levator hiatus during instruction of pelvic floor or
      transversus abdominis contraction: a 4D ultrasound study.
AB  - A new theory claims that the pelvic floor muscles (PFM) can be trained via the
      transversus abdominis (TrA). The aim of the present study was to compare the
      effect of instruction of PFM and TrA contraction on constriction of the levator
      hiatus, using 4D perineal ultrasonography. Thirteen women with pelvic organ
      prolapse participated in the study. Perineal ultrasound in standing position was
      used to assess constriction of the levator hiatus. Analyses were conducted off
      line with measurements in the axial plane of minimal hiatal dimensions. The
      reduction of all the hiatal dimensions was significantly greater during PFM than
      TrA contraction. All patients had a reduction of the levator hiatus area during
      PFM contraction (mean reduction 24.0%; range 6.1-49.2%). In two patients, there
      was an increase of the levator hiatus area during TrA contraction. Instruction of
      PFM contraction is more effective than TrA contraction.

PMID- 18806913
TI  - [Situation of nursing home residents with continence problems: a study in two
      German nursing homes].
AB  - AIM OF THE STUDY: To describe the situation of residents with continence problems
      (CP) in two German nursing homes. METHODS: Medical and nursing records of all
      residents were reviewed and categorised according to a standardised protocol.
      Structured interviews were performed with the responsible nursing staff of each
      resident. Qualitative methods like focus groups and participating observations
      were used to collect further information. RESULTS: In the investigated nursing
      homes 177 residents with and 70 without CP were identified (81.5% women; mean age
      83.7 years). For these 247 residents 57 physicians and 116 nurses or nurses-aides
      were in charge. 71% of female and 76% of male residents had at least one CP. The
      three most common CP among residents were combined urinary and faecal
      incontinence (32%), urinary incontinence (21%), and urinary catheters (17%).
      Residents with CP were significantly more dependent in functional abilities like
      toileting, dressing or cognitive function than those without CP (P<0.01). In a
      high proportion of residents with CP physicians (64%) were not consulted nor were
      relatives (86%) involved in continence related activities. CONCLUSION: Nursing
      home residents are commonly affected by continence problems which are associated
      with functional dependency and relevant co-morbidity. The public and expert
      debate on continence problems of nursing home residents has to be promoted to
      achieve long-term changes.

PMID- 18806914
TI  - Fear of heights: cognitive performance and postural control.
AB  - INTRODUCTION: Fear of heights, or acrophobia, is one of the most frequent
      subtypes of specific phobia frequently associated to depression and other anxiety
      disorders. Previous evidence suggests a correlation between acrophobia and
      abnormalities in balance control, particularly involving the use of visual
      information to keep postural stability. This study investigates the hypotheses
      that (1) abnormalities in balance control are more frequent in individuals with
      acrophobia even when not exposed to heights, that (2) acrophobic symptoms are
      associated to abnormalities in visual perception of movement; and that (3)
      individuals with acrophobia are more sensitive to balance-cognition interactions.
      METHOD: Thirty-one individuals with specific phobia of heights and thirty one non
      phobic controls were compared using dynamic posturography and a manual tracking
      task. RESULTS: Acrophobics had poorer performance in both tasks, especially when
      carried out simultaneously. Previously described interference between posture
      control and cognitive activity seems to play a major role in these individuals.
      DISCUSSION: The presence of physiologic abnormalities is compatible with the
      hypothesis of a non-associative acquisition of fear of heights, i.e., not
      associated to previous traumatic events or other learning experiences.
      Clinically, this preliminary study corroborates the hypothesis that vestibular
      physical therapy can be particularly useful in treating individuals with fear of
      heights.

PMID- 18806915
TI  - Association of the s allele of the 5-HTTLPR with neuroticism-related traits and
      temperaments in a psychiatrically healthy population.
AB  - INTRODUCTION: Research concerning the genetic background of traits, temperaments
      and psychiatric disorders has been rapidly expanding. One of the most frequently
      studied genetic polymorphisms in the background of psychological and psychiatric
      phenomena is the 5-HTTLPR polymorphism of the serotonin transporter gene which
      has earlier been found to be associated with neuroticism and neuroticism-related
      traits and disorders. However, both the neuroticism trait and psychiatric
      disorders are complex and composed of several subfacets. The aim of our study was
      to investigate the association of the 5-HTTLPR polymorphism with several smaller,
      distinct and better characterisable phenomena related to the neuroticism trait.
      METHODS: 169 healthy females participated in the study. All participants
      completed the Buss-Durkee Hostility Inventory (BDHI), the State-Trait Anxiety
      Inventory (STAI), The Zung Self-rating Depression Scale (ZSDS), the Beck
      Hopelessness Scale, the SCL-51, the Temperament and Character Inventory (TCI) and
      the Temperament Evaluation of Memphis, Pisa, Paris and San Diego (TEMPS-A)
      questionnaire. All subjects were genotyped for the 5-HTTLPR using PCR. Data were
      analysed with ANOVA and MANCOVA with age as a covariate. RESULTS: We found that
      the presence of the s allele was significantly associated with anxiety,
      depression, hopelessness, guilt, hostility, aggression, presence of neurotic
      symptoms, self-directedness and affective temperaments carrying a depressive
      component even when controlling for age. CONCLUSIONS: Our study is the first that
      confirms that traits and characteristics related to neuroticism, such as
      increased anxiety, depression, hopelessness, somatization, feeling of guilt,
      hostility, aggression, lack of self-directedness and affective temperament are
      consistently and independently associated with the 5-HTTLPR polymorphism of the
      serotonin transporter gene. Our study therefore suggests that neuroticism can be
      considered a unified construct not only from a phenotypical but also from a
      genetic point of view and 5HTTLPR can be considered one component of its
      polygenic background. Our results thus yield further insight into the role of the
      5-HTTLPR in the background of neuroticism and neuroticism-related psychiatric
      disorders.

PMID- 18806916
TI  - Attention deficit/hyperactivity disorder in female offenders: prevalence,
      psychiatric comorbidity and psychosocial implications.
AB  - Attention deficit-/hyperactivity disorder (ADHD) is associated with social
      maladaptation and delinquency in later life. This study was conducted to
      determine the prevalence of ADHD and comorbid conditions in female prison
      inmates. One hundred and ten adult female prison inmates of a German prison for
      women were investigated. SCID-I and -II interviews and standardized German
      instruments for the assessment of ADHD in adults (HASE) were used. The lifetime
      prevalence of ADHD was 24.5 and 10% for persisting ADHD according to DSM-IV
      criteria. A decline of the prevalence of persisting ADHD with age from 17.9% (age
      <25 years) to 10% (age 26-45 years) and 0% (age >45 years) was observed. Female
      prisoners with ADHD were younger at their first conviction as compared with
      females without ADHD and they showed longer incarceration periods in relation to
      age. The prevalence of other axis I disorders was high in both the ADHD and the
      non-ADHD female population, but significantly higher in ADHD females. Mean number
      of axis I diagnoses was 3.6 in females with ADHD and 2.3 in females without ADHD.
      No differences were found between females with and without ADHD regarding the
      prevalence of psychotic, affective, anxiety, somatization and posttraumatic
      disorders. Substance use disorders and in particular the use of stimulants were
      more frequent in females with ADHD as well as borderline personality disorder and
      eating disorders. The results suggest a high prevalence of ADHD in female
      prisoners that exceeds the prevalence estimates from epidemiological studies in
      general female populations. Moreover, it appears that ADHD is particularly
      frequent in adolescent and young adult female offenders and increases the risk
      for further psychiatric morbidity. The results indicate the need of adequate
      psychiatric support of female prison inmates including therapeutic programs for
      ADHD.

PMID- 18806917
TI  - Substantia nigra hyperechogenicity in depressive subjects relates to motor
      asymmetry and impaired word fluency.
AB  - BACKGROUND: Substantia nigra hyperechogenicity (SNH) is a characteristic
      transcranial sonography (TCS) finding in Parkinson's disease (PD). SNH, found
      also in about 10% of healthy adults, was related to a subclinical malfunction of
      the nigrostriatal dopaminergic system on positron emission tomography studies.
      Both, liability for developing PD and frequency of SNH were found to be increased
      in depressed subjects. Here, we investigated whether SNH in depression is related
      to motor or cognitive abnormalities resembling early PD. METHODS: Fourty-one
      patients with major depressive disorder and 15 with adjustment disorder with
      depressed mood were studied clinically and with TCS. RESULTS: Frequency of SNH
      was similar in both groups (39, 33%; Chi-square test, P = 0.70). Larger SN
      echogenic size correlated with larger right-to-left asymmetry of finger tapping
      (Spearman test, r = 0.37, P = 0.009) and lower verbal fluency (r = -0.35, P =
      0.038). These correlations were stronger in patients at ages >/= 50 years (r =
      0.52, P = 0.007; r = -0.50, P = 0.020), and, independently from age, in patients
      with reduced echogenicity of brainstem raphe suggested to reflect alteration of
      the serotonergic system (r = 0.40, P = 0.045; r = -0.51, P = 0.044). Whereas
      bilateral sum score of finger tapping was negatively correlated with severity of
      depression on the beck depression inventory (r = -0.50, P = 0.001) and the
      Hamilton depression rating scale (r = -0.34, P = 0.019), no correlation was found
      between depression severity and tapping asymmetry, or between depression severity
      and verbal fluency. CONCLUSION: Data suggest that TCS detects a subgroup of
      patients with depression characterized by symptoms of early parkinsonism who are
      possibly at an elevated risk of later developing definite PD.

PMID- 18806918
TI  - Factors associated with choice of psychotropic drugs used for intentional drug
      overdose.
AB  - INTRODUCTION: Knowledge of the factors influencing the choice of drugs used for
      intentional drug overdose (IDO) may allow the reduction of IDO lethality.
      OBJECTIVES: To assess with which frequency subjects with intentional overdose of
      psychotropic drugs ingest their own psychotropic drug treatment, and whether
      prescription of a drug may be a factor influencing the choice of drugs used for
      the IDO. METHODS: Demographic characteristics, psychiatric history, and currently
      prescribed psychotropic drug treatment were collected for all the patients (n =
      1,654) admitted to an emergency department (ED) for IDO with psychotropic drugs
      (anxiolytics, hypnotics, antidepressants, neuroleptics and mood stabilizers) over
      a period of 18 months. Drugs ingested for the IDO were compared in subjects who
      had ingested at least one psychotropic drug that was prescribed for them and
      subjects who had ingested psychotropic drugs not prescribed for them using
      multivariate logistic regression. RESULTS: Two-thirds of the patients ingested
      during the IDO at least one of their own prescribed psychotropic drugs. Compared
      with the subjects who had ingested psychotropic drugs not prescribed for them,
      they were more likely to have a history of psychiatric hospitalization (OR 4.2;
      95%CI 3.1-5.5), of being a psychiatric outpatient (OR 3.9; 95%CI 3.0-5.1), of
      parasuicide (OR 2.5; 95%CI 1.9-3.3) and a serious IDO (OR 2; 95%CI 1.4-2.9).
      Independently from age and psychiatric hospitalization history, they ingested
      during the IDO more often antidepressants (OR 4.4; 95%CI 3.0-6.4), antipsychotics
      (OR 2.9; 95%CI 1.7-4.8) and mood stabilizers (OR 4.1; 95%CI 1.6-10.7). No
      association was found with prescription for overdose of hypnotic (OR 1.1; 95%CI
      0.8-1.5), anxiolytic (OR 1.2; 95%CI 0.9-1.7) or paracetamol (OR 1.0; 95%CI 0.5
      2.1). CONCLUSION: Prescription of the psychotropic drugs plays an important role
      in the choice of the drugs ingested for the IDO. It might make potentially
      "dangerous" drugs available for the patient. Physicians have always to balance
      the benefit of the treatment against the risk of drug overdose.

PMID- 18806919
TI  - Inverse association of cortisol serum levels with T-tau, P-tau 181 and P-tau 231
      peptide levels and T-tau/Abeta 1-42 ratios in CSF in patients with mild
      Alzheimer's disease dementia.
AB  - Hypercortisolemia and increased levels of hyperphosphorylated tau proteins in
      cerebrospinal fluid (CSF) are common features with pathogenic relevance in
      Alzheimer;s disease (AD). Experimental studies point to an influence of cortisol
      on Abeta and tau pathology in AD. Association of both parameters have not yet
      been described in a sample of AD patients. In the present study, serum levels of
      cortisol were determined in 26 patients with mild AD dementia and 20 age-matched
      healthy elderly controls by ELISA. In addition, we measured in AD patients CSF
      levels of cortisol, total tau (T-tau), tau phosphorylated at threonine 181 (P-tau
      181), tau protein phosphorylated at threonine 231 (P-tau 231) and beta-Amyloid
      (Abeta) 1-42 and determined T-tau/Abeta 1-42 ratios in CSF. We found in AD
      patients significantly increased cortisol serum levels (551.4 +/- 146.1 nmol/l; P
      = 0.002) as compared to healthy controls (435.3 +/- 83.9 nmol/l). In AD patients,
      cortisol serum levels were significantly inversely correlated with T-tau (r = 
      0.496; P = 0.01), P-tau 181 (r = -0.558; P = 0.003) and P-tau 231 (-0.500; P =
      0.009) protein levels and T-tau/Abeta 1-42 ratios (r = -0.450; P = 0.021) in CSF.
      In addition, cortisol serum levels showed a trend of positive correlation with
      Abeta 1-42 CSF levels (r = 0.386; P = 0.052). However, no significant
      correlations of cortisol serum with CSF levels as well as cortisol CSF levels
      with CSF biomarkers could be detected in AD patients. In conclusion, our results
      show that increased cortisol serum but not CSF levels are associated with minor
      signs of AD pathology in CSF, indicating a putative neuroprotective effect of
      moderately elevated cortisol serum levels in patients with mild AD dementia.

PMID- 18806920
TI  - Neuregulin 1 ICE-single nucleotide polymorphism in first episode schizophrenia
      correlates with cerebral activation in fronto-temporal areas.
AB  - The Neuregulin (NRG1) gene has been associated with schizophrenia, but its
      functional implications are largely unknown. Our aim was to assess differential
      brain activation between patients carrying an at-risk allele on the Neuregulin 1
      gene and patients without this genetic risk. Neural signal changes between 14
      first episode schizophrenia patients with the at risk allele (SNP8NRG221533) from
      the Icelandic core haplotype and 14 without were measured with fMRI during a
      working memory task. Patients without the at risk allele showed greater
      activations (P < 0.05; corrected) in the left hippocampus, precuneus and
      cerebellum, as well as the right anterior cingulate. Brain regions previously
      associated with the pathology of Schizophrenia are differentially affected in
      those with a genetic at risk status in the NRG1 gene. Heterogeneity of structural
      and functional measures within patients characterized by clinical phenotypes may
      be in part due to this genetic variation.

PMID- 18806921
TI  - Does psychomotor agitation in major depressive episodes indicate bipolarity?
      Evidence from the Zurich Study.
AB  - BACKGROUND: Kraepelin's partial interpretation of agitated depression as a mixed
      state of "manic-depressive insanity" (including the current concept of bipolar
      disorder) has recently been the focus of much research. This paper tested
      whether, how, and to what extent both psychomotor symptoms, agitation and
      retardation in depression are related to bipolarity and anxiety. METHOD: The
      prospective Zurich Study assessed psychiatric and somatic syndromes in a
      community sample of young adults (N = 591) (aged 20 at first interview) by six
      interviews over 20 years (1979-1999). Psychomotor symptoms of agitation and
      retardation were assessed by professional interviewers from age 22 to 40 (five
      interviews) on the basis of the observed and reported behaviour within the
      interview section on depression. Psychiatric diagnoses were strictly
      operationalised and, in the case of bipolar-II disorder, were broader than
      proposed by DSM-IV-TR and ICD-10. As indicators of bipolarity, the association
      with bipolar disorder, a family history of mania/hypomania/cyclothymia, together
      with hypomanic and cyclothymic temperament as assessed by the general behavior
      inventory (GBI) [15], and mood lability (an element of cyclothymic temperament)
      were used. RESULTS: Agitated and retarded depressive states were equally
      associated with the indicators of bipolarity and with anxiety. Longitudinally,
      agitation and retardation were significantly associated with each other (OR =
      1.8, 95% CI = 1.0-3.2), and this combined group of major depressives showed
      stronger associations with bipolarity, with both hypomanic/cyclothymic and
      depressive temperamental traits, and with anxiety. Among agitated, non-retarded
      depressives, unipolar mood disorder was even twice as common as bipolar mood
      disorder. CONCLUSION: Combined agitated and retarded major depressive states are
      more often bipolar than unipolar, but, in general, agitated depression (with or
      without retardation) is not more frequently bipolar than retarded depression
      (with or without agitation), and pure agitated depression is even much less
      frequently bipolar than unipolar. The findings do not support the hypothesis that
      agitated depressive syndromes are mixed states. LIMITATIONS: The results are
      limited to a population up to the age of 40; bipolar-I disorders could not be
      analysed (small N).

PMID- 18806922
TI  - Use of self-closing U-clips for dural repair in mini-invasive surgery for
      herniated disc.
AB  - OBJECT: The feasibility of a new technique of dural repair (self-closing U-clips)
      in mini-invasive surgery for herniated disk is demonstrated in this case report.
      MATERIALS AND METHODS: A 44-year-old male patient underwent lumbar
      microdiscectomy at out Institute, with subsequent dural leak as surgical
      complication; the dural leak re-appeared even after a second intervention in
      which we used muscle and dural graft and fibrin glue to repair the leak. We then
      decided to employ self-closing nitinol- U-clip to achieve primary dural closure.
      RESULTS: After the intervention the patient no more presented signs or symptoms
      due to the unintended durotomy, and the postoperative course was uneventful.
      CONCLUSION: Self-closing nitinol U-clips (Medtronic, Inc., Minneapolis) can be
      used for closing a dural tear through a mini-invasive approach that could make a
      conventional microsuturing technique very difficult.

PMID- 18806923
TI  - Baroreflex sensitivity and power spectral analysis in different extrapyramidal
      syndromes.
AB  - Cardiac autonomic abnormalities have been described in Parkinson's disease and
      other extrapyramidal syndromes. To investigate baroreflex sensitivity as an
      important risk marker of cardiovascular mortality in patients with Parkinson's
      disease and other extrapyramidal syndromes. We recorded continuously blood
      pressure, ECG and respiration in 35 patients with multiple system atrophy (MSA),
      32 patients with progressive supranuclear palsy (PSP), 46 patients with
      idiopathic Parkinson's disease (PD) and in 27 corresponding healthy subjects
      (Con). Recordings of 2 min at rest were used to calculate baroreflex and spectral
      analysis of heart rate and systolic blood pressure. Resting baroreflex
      sensitivity (BRS) was significantly lower in the MSA and the PSP group but not in
      the PD group in comparison to the Con group. With increasing Hoehn & Yahr stage,
      BRS significantly decreased in all patient groups. In spectral analysis, all
      patient groups had a significantly lower relative low frequency (LF)-band power
      than the healthy controls. Patients with extrapyramidal disorders frequently
      demonstrate pathologically decreased BRS values and abnormalities of spectral
      analysis. This may have fundamental impact on the cardiovascular prognosis of
      patients with extrapyramidal disease.

PMID- 18806924
TI  - Change detection related to peripheral facial expression: an
      electroencephalography study.
AB  - The objective is to study the change detection of emotion expression by
      electroencephalography (EEG). A visual letter task was combined with two neutral
      faces. After a short break another letter task occurred whilst the peripheral
      faces remained or randomly changed to joy, anger or disgust. Study participants
      responded whether they had perceived a change in emotion expression or not.
      Explicit change detection elicited more positive-going EEG amplitudes than change
      blindness between 750 and 900 ms. A change to disgust elicited largest effects.
      Furthermore, evidence for implicit change detection occurred.

PMID- 18806925
TI  - Decreased M1 muscarinic receptor density in rat amphetamine model of
      schizophrenia is normalized by clozapine, but not haloperidol.
AB  - There is increasing evidence supporting the involvement of the muscarinic
      cholinergic system in schizophrenia. We examined the M1 muscarinic receptor
      density and mRNA expression in brains of a rat amphetamine model of
      schizophrenia. We also assessed the effect of the model and chronic treatment
      with haloperidol and clozapine on brain M1 receptor density and gene expression.
      A significant decrease of about 20% in the density of M1 receptor was detected in
      the cortex and in the striatum of amphetamine model rats. A significant increase
      of 33% in the density of the M1 receptor was found in the cortex and striatum of
      rats treated chronically with clozapine (0.5 mg/kg), but not with haloperidol (25
      mg/kg). Chronic clozapine, but not haloperidol, normalized the decrease in M1
      receptors observed in amphetamine model rats, in both cortex and striatum.
      Regulation of the M1 receptor may occur in a post-transcriptional phase. Our
      findings suggest involvement of both dopaminergic and cholinergic-muscarinic
      systems in the pathophysiology and pharmacotherapy of schizophrenia.

PMID- 18806926
TI  - Association of the SLC45A2 gene with physiological human hair colour variation.
AB  - Pigmentation is a complex physical trait with multiple genes involved. Several
      genes have already been associated with natural differences in human
      pigmentation. The SLC45A2 gene encoding a transporter protein involved in melanin
      synthesis is considered to be one of the most important genes affecting human
      pigmentation. Here we present results of an association study conducted on a
      population of European origin, where the relationship between two non-synonymous
      polymorphisms in the SLC45A2 gene - rs26722 (E272K) and rs16891982 (L374F) - and
      different pigmentation traits was examined. The study revealed a significant
      association between both variable sites and normal variation in hair colour. Only
      L374F remained significantly associated with hair colour when both SNPs were
      included in a logistic regression model. No association with other pigmentation
      traits was detected in this population sample. Our results indicate that the rare
      allele L374 significantly increases the possibility of having black hair colour
      (OR = 7.05) and thus may be considered as a future marker for black hair colour
      prediction.

PMID- 18806927
TI  - Treatment of refractory retrobulbar granuloma with rituximab in a patient with
      ANCA-negative Wegener's granulomatosis: a case report.
AB  - Retrobulbar granuloma is one of the serious complications in Wegener's
      granulomatosis and often shows resistance to conventional therapy during long
      term treatment. The outcome of this complication includes visual loss, orbital
      and facial deformity, fistula formation, as well as infection. There has been
      increasing evidence that shows the efficacy of rituximab, a chimeric anti-B cell
      mAb, for the treatment of autoimmune diseases including Wegener's granulomatosis.
      We present a 22-year-old Japanese woman who was diagnosed with Wegener's
      granulomatosis complicated by refractory retrobulbar granuloma. She was admitted
      to our hospital with pain of the right eye and right proptosis during treatment
      with monthly IVCY for Wegener's granulomatosis. We diagnosed refractory
      retrobulbar granuloma by computed tomography (CT) scan and biopsy. She showed a
      refractory growth of retrobulbar granuloma in spite of negative ANCA. She was
      also complicated with pulmonary granulomatous lesions in bilateral apices. After
      approval by an institutional ethical committee and informed consent of this
      patient, rituximab 375 mg/m2 was intravenously administered weekly four times.
      Concomitant prednisolone 0.5 mg/kg was also administered for 2 weeks and
      gradually tapered. Treatment of rituximab resulted in prompt relief of symptoms
      in this case and the reduction of the granuloma. BVAS score also improved from 6
      to 0 at 3 months and was kept in remission for 12 months. Circulating CD19
      positive cells were kept less than 0.1% during the follow-up. There were no
      serious adverse events. This case suggests that rituximab is effective for
      refractory retrobulbar granuloma complicated in Wegener's granulomatosis even
      when ANCA titers are negative.

PMID- 18806928
TI  - Autoreactive T-cell responses to myeloperoxidase in patients with antineutrophil
      cytoplasmic antibody-associated vasculitis and in healthy individuals.
AB  - The aim of this study was to evaluate the characteristics of autoreactive T cells
      to myeloperoxidase (MPO) in patients with MPO-antineutrophil cytoplasmic antibody
      (ANCA)-associated vasculitis. Peripheral blood T cells from 15 patients with MPO
      ANCA-associated vasculitis and 14 healthy individuals were cultured with three
      recombinant proteins that together comprised the entire MPO sequence (L, all 112
      amino acids (AA) of the light chain; HI, AA 1-227 of the heavy chain; HII, AA 212
      467 of the heavy chain), and the antigen-specific T-cell proliferative response
      was measured by 3H-thymidine incorporation. T-cell responses to MPO-L and HI were
      both detected in four patients and three healthy donors, and responses to MPO-HII
      were detected in four patients and seven healthy donors. These findings indicate
      that at least three independent T-cell epitopes exist on the MPO molecule.
      Interestingly, the patients whose T cells showed these MPO-induced responses were
      mainly in remission. Peripheral blood T cells reactive with MPO were primarily of
      the HLA-DR-restricted CD4+ phenotype. In summary, we successfully used
      recombinant MPO fragments to detect autoreactive CD4+ T cells to multiple MPO
      epitopes in blood samples from patients with MPO-ANCA-associated vasculitis and
      healthy individuals.

PMID- 18806929
TI  - Assessment of biochemical markers in patients with pain of vascular origin.
AB  - The aim of this study was to analyse blood plasma biochemical parameters in
      patients with pain of vascular origin. Blood samples were taken from 62 patients
      (38-86 years of age) with critical limb ischaemia, claudication or lower limb
      embolism, and from a control group. The samples were taken at the time of
      hospital admission, 1 h after surgery, 24 h after surgery, and before discharge.
      Pain intensity was assessed as mild, moderate or intense. The following
      biochemical parameters were measured: C reactive protein, total protein, albumin,
      total cholesterol, HDL and LDL cholesterol, glucose, triglycerides, reduced
      glutathione, malondialdehyde (MDA), and total antioxidative capacity. In the
      control subjects, MDA increased postoperatively, whereas albumin, total protein,
      HDL and total cholesterol decreased. In patients with claudication triglycerides
      and LDL cholesterol also decreased postoperatively. In patients with critical
      limb ischaemia, reduced glutathione and antioxidative capacity decreased
      postoperatively and MDA increased. Except in patients with embolism, MDA and C
      reactive protein increased following surgery. Patients with critical limb
      ischaemia and embolism reported the worst preoperative pain. In patients with
      ischaemia, intense pain persisted during the whole postoperative period while in
      patients with embolism pain continuously decreased. At different time intervals,
      pain intensity was related to different biochemical markers. We suggest that the
      described blood plasma changes might play an important role in pain assessment
      and pain management.

PMID- 18806930
TI  - Is transketolase like 1 a target for the treatment of differentiated thyroid
      carcinoma? A study on thyroid cancer cell lines.
AB  - Radioactive iodine-refractory [(18)F] fluorodeoxy-glucose-positron emission
      tomography-positive thyroid carcinomas represent especially aggressive tumors.
      Targeting glucose metabolism by the transketolase isoenzyme transketolase like 1
      (TKTL-1) which is over-expressed in various neoplasms, may be effective. The
      correlation of TKTL-1 expression and the response to oxythiamine as the currently
      best-characterized inhibitor of transketolases was studied in differentiated
      thyroid cancer cell lines. We determined TKTL-1 expression, proliferation,
      glucose uptake and GLUT-1 expression in non-treated thyroid cells and recorded
      the effect of oxythiamine on iodide uptake and on thymidine uptake. TKTL 1 was
      highest expressed in cell lines derived from more invasive tumors but the
      expression level was not strongly correlated to proliferation rate, to GLUT-1
      expression or to the response to oxythiamine. Oxythiamine showed only a weak
      effect in the TKTL-1 expressing cell lines. Over-expression of TKTL-1 is not an
      indicator for responsiveness to oxythiamine. More specific inhibitors should be
      tested.

PMID- 18806931
TI  - Agreement between clinical estimation and a new quantitative analysis by
      Photoshop software in fundus and angiographic image variables.
AB  - PURPOSE: To evaluate the validity of a new method for the quantitative analysis
      of fundus or angiographic images using Photoshop 7.0 (Adobe, USA) software by
      comparing with clinical evaluation. METHODS: Four hundred and eighteen fundus and
      angiographic images of diabetic patients were evaluated by three retina
      specialists and then by computing using Photoshop 7.0 software. Four variables
      were selected for comparison: amount of hard exudates (HE) on color pictures,
      amount of HE on red-free pictures, severity of leakage, and the size of the
      foveal avascular zone (FAZ). RESULTS: The coefficient of agreement (Kappa)
      between the two methods in the amount of HE on color and red-free photographs
      were 85% (0.69) and 79% (0.59), respectively. The agreement for severity of
      leakage was 72% (0.46). In the two methods for the evaluation of the FAZ size
      using the magic and lasso software tools, the agreement was 54% (0.09) and 89%
      (0.77), respectively. Agreement in the estimation of the FAZ size by the lasso
      magnetic tool was excellent and was almost as good in the quantification of HE on
      color and on red-free images. CONCLUSION: Considering the agreement of this new
      technique for the measurement of variables in fundus images using Photoshop
      software with the clinical evaluation, this method seems to have sufficient
      validity to be used for the quantitative analysis of HE, leakage, and FAZ size on
      the angiograms of diabetic patients.

PMID- 18806932
TI  - Preventive role of magnesium on skeletal muscle ischemia-reperfusion injury-an
      experimental study.
AB  - The present study aims to explore whether Mg infusion has a preventive effect on
      ischemia-reperfusion injury in rats. A total of 20 Sprague-Dawley-type adult male
      rats were used. In group 1 (control), 0.9% isotonic solution was administered. In
      group 2 (experiment), magnesium sulfate (0.5 mg per 100 g) was administered.
      Ischemia was induced for 15 min for the two groups. Magnesium (Mg), interleukin 8
      (IL-8), and malondialdehyde levels were analyzed in blood, while edema,
      neutrophil infiltration, eosinophilia, loss of striation, and nucleolization were
      evaluated in histopathological examination. Mg levels in the experiment group
      were higher than those in the control group after ischemia-reperfusion (p <
      0.05). In the control group, postischemia and postreperfusion IL-8 values were
      higher than preoperative values (p < 0.05). As for eosinophilia and loss of
      striation values, these were higher in the experiment group after ischemia
      reperfusion than the values in the control group (p < 0.05). Histopathologically,
      Mg infusion cannot prevent the tissue injury triggered in ischemia-reperfusion
      periods. Eosinophilia can be one of the major and earliest markers of ischemia
      reperfusion injury.

PMID- 18806933
TI  - Age-based differences in hair zinc of Vancouver preschoolers.
AB  - Marginal zinc deficiency (MZD), the subclinical stage of zinc deficiency, is
      common in industrialized societies. Serum zinc, the most common biomarker of zinc
      status, lacks sensitivity and specificity to diagnose this deficiency. Hair zinc,
      however, is sensitive and specific enough to detect MZD in children. Differences
      in hair zinc associated with age and sex have been reported. These differences
      have not been investigated thoroughly; therefore, interpretation of the results
      of hair analyses is difficult. This cross-sectional study was designed to examine
      the hair zinc status of a group of Vancouver preschoolers (24-71 months) and
      assess the age- and sex-based differences in their hair zinc. Hair samples were
      obtained (n = 719) and analyzed for zinc using inductively coupled plasma mass
      spectrometry. Our results indicated a mean hair zinc of 115 +/- 43 microg/g with
      17% below the low hair zinc cutoff (70 microg/g). Boys and girls had comparable
      mean hair zinc, while girls had a significantly higher occurrence of low hair
      zinc than boys (21% vs. 12%). Children <4 years of age had significantly lower
      mean hair zinc and higher rate of low hair zinc compared to children > or =4. Our
      study provides important reference values for the hair zinc of healthy North
      American preschoolers.

PMID- 18806934
TI  - IRF8 regulates myeloid and B lymphoid lineage diversification.
AB  - Interferon regulatory factor 8 (IRF8) is a member of the IRF family of
      transcription factors whose members play critical roles in interferon (IFN)
      signaling pathways governing the establishment of innate immune responses by
      myeloid and dendritic cells. IRF8 is also expressed in lymphoid cells and recent
      studies have documented its involvement in B cell lineage specification,
      immunoglobulin light chain gene rearrangement, the distribution of mature B cells
      into the marginal zone and follicular B cell compartment, and the transcriptional
      regulation of critical elements of the germinal center reaction. Here we review
      the contributions of IRF8 to B cell development from hematopoietic stem cells in
      the bone marrow and its place in the hierarchical regulatory network governing
      specification and commitment to the B cell fate.

PMID- 18806935
TI  - Inducing the T cell fates required for immunity.
AB  - A naive T cell recruited into an immune response receives its critical inductive
      signals in the lymph node. The selected T cell must then produce cellular progeny
      empowered with new functions. Differentiated effector cells divide and migrate to
      infected tissues with an imprint of the instructions delivered to their
      progenitor. Some progeny of a selected naive T cell, however, must remain
      undifferentiated and persist as lymph node-dwelling memory cells to replace and
      fortify defense should the intruder return. The integration of cell division,
      differentiation, diversification, and four-dimensional navigation make the clonal
      burst of a T cell in reaction to microbial invasion an exciting problem of
      developmental biology, cellular adaptation to environmental cues, and the
      propagation of signaling pathways through space and time. Epigenetic control of
      gene expression and an ancient cellular diversification mechanism called
      asymmetric cell division have recently been proposed to explain how a selected T
      cell can accomplish its imposing tasks. Future investigations will be directed
      toward understanding the mechanisms that allow a selected T cell to produce
      daughter T cells that are different, that are capable of remembering their
      inductive history, and that fulfill the demand for acute function and
      regeneration.

PMID- 18806936
TI  - Advances in treatment for chronic granulomatous disease.
AB  - Chronic granulomatous disease (CGD) is a rare congenital disorder resulting from
      a failure of neutrophils to produce oxidases. Patients are therefore prone to
      recurrent infections from various organisms including fungi and atypical
      bacteria. The mortality in patients with the X-linked form of CGD, the most
      common type, ranges from 3% to 5% per year and although management of infections
      has improved with advances in antimicrobial therapies, better methods are needed
      to be able to cure these patients. Peripheral blood stem cell or bone marrow
      transplantation, while curative, is not widely used due to the episodic nature of
      the infections and the belief by many that conservative management is preferable
      to the risks of transplantation. Still, as will be discussed, improvements in the
      field are making allogenic transplantation more desirable and tilting the risk
      benefit ratio in favor of this modality. Additionally, gene therapy, which has
      been a long touted method to cure CGD, has within the last 5-10 years become more
      and more of a reality and may be realized by the end of this decade.

PMID- 18806937
TI  - Abstracts of the Joint Annual Meeting of Immunology of the Austrian and German
      Societies (OGAI, DGfI). Vienna, Austria. September 3-6, 2008.

PMID- 18806938
TI  - Standard "inject and cut" endoscopic mucosal resection technique is practical and
      effective in the management of superficial colorectal neoplasms.
AB  - BACKGROUND: Standard polypectomy techniques may be contributing to ineffective
      eradication of colonic superficial neoplasia, an increasing number of which are
      nonpolypoid. We aimed to demonstrate the practicality and efficacy of the "inject
      and cut" endoscopic mucosal resection (EMR) technique in routine clinical
      practice. METHODS: Colonic EMRs performed for polypoid and nonpolypoid lesions at
      a tertiary institution were prospectively collected and analyzed for efficacy,
      and short and long-term complications. RESULTS: 224 colonic neoplasms (143 flat,
      65 sessile and 16 subpedunculated) were excised by the standard inject-and-cut
      method, with standard accessories. The median size of all lesions was 10 mm
      (range 2-50 mm) and 110 (49.2%) lesions were located in the proximal colon.
      Histological completeness of resection was achieved in 87% of cases. Of the
      lesions 77.2% were dysplastic, with 5 cases of carcinoma in situ and 18 severely
      dysplastic adenomas. Complications included bleeding in five cases (2.2 %) and a
      single case of perforation (0.4%). All complications were managed endoscopically.
      Median follow up at 24 +/- 16 months (range 12-84 months) revealed a 7.2% local
      recurrence rate, all of which were subsequently eradicated by repeat EMR.
      CONCLUSIONS: Standard inject-and-cut colonic EMR is practical and effective in
      the eradication of superficial colonic neoplasia.

PMID- 18806939
TI  - Neuromonitoring and video-assisted thyroidectomy: a prospective, randomized case
      control evaluation.
AB  - INTRODUCTION: This study evaluates the role of intraoperative neuromonitoring
      (IONM) in video-assisted thyroidectomy (VAT) with emphasis given to the
      identification of recurrent laryngeal nerve (RLN) and external branch of superior
      laryngeal nerve (EBSLN). METHODS: The study was based on a prospectively
      randomized series comprising 72 standard VAT gasless approaches. In the control
      group (N = 36), the laryngeal nerves were identified by 30 degrees 5-mm endoscope
      magnification solely. The standard technique of the IONM group (N = 36) consisted
      of localizing and monitoring EBSLN, both vagus and RLNs, before and after thyroid
      resection to prove nerve integrity. Surgical outcomes were mean operative time,
      nerve representation, incision length, and morbidity. RESULTS: All procedures
      were performed successfully. There were no instances of equipment malfunction or
      interference. No permanent complications occurred in either group. The incidences
      of temporary RLN injury were 2.7% (1 patient) and 8.3% (3 patients) in the IONM
      and control group, respectively. The EBSLN was identified better in the IONM
      group: 83.6% versus 42% (p < 0.05). In the IONM group, a negative
      electromyography (EMG) response indicated an altered function of RLN and stage
      thyroidectomy was scheduled. CONCLUSIONS: This is the first VAT series with a
      standardized IONM technique. The technical feasibility and safety of IONM in
      selected patients seem acceptable. Neuromonitoring during VAT is effective in
      providing identification and function of laryngeal nerves. IONM enables surgeons
      to feel more comfortable with their approach to VAT. A reduction of rates for
      postoperative complications could not be demonstrated in the present study.
      Larger series are needed for further evaluation.

PMID- 18806940
TI  - Female gender may give rise to difficulties in endoscopic and laparoscopic
      biliary surgery.

PMID- 18806941
TI  - Assessment of pain by face scales after gastrectomy: comparison of
      laparoscopically assisted gastrectomy and open gastrectomy.
AB  - BACKGROUND: Laparoscopic gastrectomy is reported to cause little pain. However,
      only the total number of analgesics used has been studied to date. Because pain
      is a subjective experience, its evaluation requires indicators for the subjective
      assessment. METHODS: Pain was evaluation for patients after open distal
      gastrectomy (ODG, 52 cases), laparoscopically assisted distal gastrectomy (LADG,
      112 cases), open total gastrectomy (OTG, 18 cases), and laparoscopically assisted
      total gastrectomy (LATG, 33 cases). The patients were administered continuous
      epidural anesthesia for 2 days after the surgery. The Wong-Baker FACES pain
      rating scale was used to evaluate the differences in pain. Each patient was
      evaluated from postoperative day (POD) 1 to POD 7, and temporal changes in pain
      were studied comparatively between ODG and LADG and between OTG and LATG.
      RESULTS: Peak pain scores were recorded on POD 3 for both distal and total
      gastrectomy. The scores decreased over time after POD 3. There was no significant
      difference in scores between open and laparoscopic gastrectomy up to POD 2, but
      lower scores were shown on PODs 3, 4, and 5 for LADG and on days 3 and 4 for
      LATG. CONCLUSIONS: The pain score for laparoscopic gastrectomy was low. There was
      no significant difference in pain between procedures while epidural anesthesia
      was in effect. Pain subsided earlier with laparoscopic than with open
      gastrectomy. The same characteristics were observed with both LADG and LATG.

PMID- 18806942
TI  - The use of composite meshes in laparoscopic repair of abdominal wall hernias: are
      there differences in biocompatibily?: experimental results obtained in a
      laparoscopic porcine model.
AB  - INTRODUCTION: In recent years, laparoscopic repair of abdominal wall hernias has
      become increasingly established in routine clinical practice thanks to the myriad
      advantages it confers. Apart from the risk of intestinal damage following
      adhesiolysis, to date no information is available on the best way of preventing
      the formation of new adhesions in the vicinity of the implanted meshes. Numerous
      experimental investigations, mainly conducted on an open small-animal model, have
      demonstrated the advantages of coating meshes, inter alia with absorbable
      materials, compared with uncoated polypropylene meshes. In our established
      laparoscopic porcine model we set about investigating three of these meshes,
      which are already available on the market. MATERIALS AND METHODS: In total, 18
      domestic pigs underwent laparoscopic surgery and three different composite meshes
      were tested in each case on six animals (Dynamesh IPOM, Proceed, Parietene
      Composite). At 4 months, postmortem diagnostic laparoscopy was carried out,
      followed by full-wall excision of the specimens. Planimetric analysis was
      conducted to investigate the size of the entire surface area and the extent of
      adhesions. Histological investigations were performed on five sections for each
      specimen. These focused on the partial volumes of inflammatory cells, the
      proliferation marker Ki67, apoptotic index, inflammatory cell marker CD68 and
      transforming growth factor beta (TGF-beta) as a marker of the extracellular
      matrix. RESULTS: A similar value of 14% was obtained for shrinkage of Dynamesh
      IPOM and Parietene Composite, while Proceed showed a 25% reduction in its surface
      area. Markedly lower values of 12.8% were obtained for Parietene Composite in
      respect of adhesions to the greater omentum, compared with 31.7% for Proceed and
      33.2% for Dynamesh IPOM (p = 0.01). Overall, Parietene Composite performed best
      in the histological and immunhistochemistry tests. CONCLUSIONS: On the whole, all
      composite meshes showed evidence of good biocompatibility. However, none of the
      coatings was completely able to prevent adhesions. Coating of polypropylene
      meshes with collagen appears to confer significant advantages compared with other
      coatings.

PMID- 18806943
TI  - Improvement of restrictive and obstructive pulmonary mechanics following
      laparoscopic bariatric surgery.
AB  - BACKGROUND: Morbidly obese patients often have impaired respiratory mechanics
      leading to restrictive and obstructive lung diseases. Weight loss after bariatric
      surgery has been shown to improve or resolve many obesity-related comorbidities.
      However, few studies have examined long-term changes in pulmonary mechanics after
      bariatric surgery. We hypothesize that pulmonary function improves after
      surgically induced weight loss. METHODS: We examined the pulmonary function of
      104 morbidly obese patients who underwent laparoscopic gastric bypass or gastric
      banding. Pulmonary studies, including forced expiratory volume in 1 s (FEV(1)),
      forced vital capacity (FVC), peak expiratory flow (PEF), and forced expiratory
      volume at midexpiratory phase (FEV(25-75%)) were measured preoperatively and at 3
      month intervals. All results are expressed as a percentage of the baseline
      values. RESULTS: There were 80 females and 24 males with a mean age of 41 years.
      The mean body mass index was 48 kg/m(2). The mean percentage of excess body
      weight loss at 12 months was 54%. At 12 months postoperatively, restrictive
      pulmonary mechanics significantly improved as demonstrated by an increase in the
      FEV(1) to 112% of baseline value, increase in the FVC to 109% of baseline value,
      increase in the PEF to 115% of baseline value, and increase in the FEV(25-75%) to
      130% of baseline value. Additionally, the percentage of patients with obstructive
      lung pattern (FEV(1)/FVC ratio less than 0.8) decreased from 9.6% preoperatively
      to 1.9% postoperatively (p=0.03). CONCLUSIONS: Weight loss after laparoscopic
      gastric bypass significantly improves restrictive and obstructive respiratory
      mechanics. The improvements were observed as early as 3 months postoperatively.

PMID- 18806944
TI  - High-frequency epicardial ultrasound: review of a multipurpose intraoperative
      tool for coronary surgery.
AB  - BACKGROUND: In open-chest coronary artery bypass grafting (CABG), the surgeon
      faces several intraoperative challenges: (1) to locate the target coronary
      artery, (2) to select the optimal anastomotic site, and (3) to assess the quality
      of the graft and distal anastomosis. Endoscopically, these three diagnostic aims
      are particularly challenging. METHODS: We reviewed the literature on the
      intraoperative application of high-frequency (6.5-15 MHz) epicardial ultrasound
      (ECUS) in CABG to aid in these challenges. RESULTS: Overall, ECUS was used in 628
      patients to visualize and assess 912 (segments of) coronary arteries, as well as
      418 grafts and distal anastomoses. In 96 cases, ECUS successfully located a
      coronary artery that was buried in the epicardial and/or myocardial tissue. In
      37/155 (24%) imaged anastomotic sites, an alternative site free of pathology was
      selected. For quality assessment of the coronary anastomosis, experimental
      validation of ECUS included 218 anastomoses in ex vivo and animal models. ECUS
      showed high sensitivity (0.98) and specificity (1.00) for detection of
      anastomotic construction errors in 120 ex vivo anastomoses. In 418 grafts and
      distal anastomoses evaluated in patients, irregularities leading to revision were
      detected in 8 (1.9%) anastomoses and minor irregularities in an additional 23
      (5.5%) anastomoses. However, little is known about the effect on long-term
      patency of specific anastomotic abnormalities revealed by ECUS. Scanning of
      arteries and anastomoses required several minutes. Current size ultrasound probes
      allowed successful experimental robot-assisted endoscopic application of ECUS.
      CONCLUSIONS: CABG may be facilitated and improved in several ways by
      intraoperative high-frequency epicardial ultrasound scanning. Totally endoscopic
      CABG may benefit from ultrasound diagnostics in particular.

PMID- 18806945
TI  - Bands and bypasses: 30-day morbidity and mortality of bariatric surgical
      procedures as assessed by prospective, multi-center, risk-adjusted ACS-NSQIP
      data.
AB  - BACKGROUND: Previous multi-institution comparisons of open and laparoscopic Roux
      en-Y gastric bypass (ORYGB and LRYGB), and laparoscopic adjustable gastric
      banding (LAGB) have been limited by the lack of unique current procedural
      terminology (CPT) codes. Specific codes have been available for LRYGB and LAGB
      since 2005 and 2006, respectively. We compare the short-term safety of these
      procedures, using risk-adjusted clinical data from a multi-institutional quality
      improvement program. METHODS: The America College of Surgeons National Surgical
      Quality Improvement Program (ACS-NSQIP) Participant Use File (PUF) was used to
      compare patients undergoing LRYGB with those undergoing ORYGB or LAGB. RESULTS:
      ORYGB versus LRYGB: The 2-year study period (2005-2006) included 5,777 patients
      (ORYGB = 1,146, LRYGB = 4,631). Patients undergoing ORYGB experienced a higher 30
      day incidence of mortality (0.79% vs. 0.17%; p = 0.002), major complications rate
      (7.42% vs. 3.37%; p < 0.0001), any complication rate (13.18% vs. 6.69%; p <
      0.0001), return visits to the OR (4.97% vs. 3.56%; p = 0.032), and longer
      postoperative length of stay (LOS) (median 3 vs. 2 days; p < 0.0001). After risk
      adjustment, ORYGB continued to demonstrate higher odds of major complication (OR
      = 2.04; [1.54, 2.69]). LAGB versus LRYGB: Analysis of 1 year of data from 2006
      included 4,756 patients (LRYGB = 3,580, LAGB = 1,176). Those treated with LAGB
      experienced an equivalent 30-day mortality (0.09% vs. 0.14%; p = 1.0), and a
      lower rate of major complications (1.0% vs. 3.3%; p < 0.0001), any complication
      (2.6% vs. 6.7%; p < 0.0001), return visits to the OR (0.94% vs. 3.6%; p <
      0.0001), and shorter postoperative LOS (median 1 vs. 2 days; p < 0.0001). Risk
      adjustment showed that LAGB was associated with a lower major complication odds
      (OR = 0.29; [0.16, 0.53]). CONCLUSIONS: Compared with LRYGB, ORYGB is associated
      with higher 30-day mortality and higher risk-adjusted major complication rate.
      While ORYGB may sometimes be indicated, a laparoscopic approach may be safer for
      RYGB when feasible. LAGB, compared with LRYGB, has a similarly low mortality rate
      and a small but statistically significant decrease in risk-adjusted 30-day
      complications. Clinical efficacy and long-term outcomes will need to be evaluated
      to determine superiority between these procedures.

PMID- 18806946
TI  - The paradox of the pouch: prompt emptying predicts improved weight loss after
      laparoscopic Roux-Y gastric bypass.
AB  - INTRODUCTION: The utility of routine upper gastrointestinal (UGI) evaluations
      after laparoscopic Roux-Y gastric bypass (LRYGB) has yet to be determined,
      primarily being used to rule out a gastrojejunal leak. Additional information can
      be assessed with these studies, including the rate of contrast emptying from the
      pouch; some patients show no or very slow emptying while others show a faster
      rate of emptying. No or slow emptying is likely due to anastomotic edema and/or a
      small initial stomal diameter. The aim of this study is to ascertain whether
      initial pouch emptying (or lack thereof) predicts postoperative weight loss.
      METHODS: Between August 2002 and July 2006, 405 LRYGB were performed by a single
      surgeon using a linear stapler technique. Patient demographics were entered into
      a longitudinal, prospective database. All patients had an UGI study on
      postoperative day 1. At 1-year follow-up, 304 patients were available for
      analysis. The patients were divided into two groups: group A, 188 patients with
      normal gastric emptying, and group B, 116 patients with very slow or no emptying
      of contrast. Analysis of covariance (ANCOVA) was used to compare weight loss
      between the two groups. The following covariates were considered in all analyses:
      age, sex, length of stay, and operative time. RESULTS: There was a statistically
      significant difference in weight loss between the two gastric emptying groups
      adjusting for age, sex, and operative time (p=0.007). Subjects with prompt
      gastric emptying (group A) showed more weight loss (50.6 kg versus 47.3 kg) and
      greater body mass index (BMI) loss (mean loss of 18.1 versus mean loss of 16.6
      kg/m(2)) when compared with group B patients with slow or no emptying of the
      gastric pouch. CONCLUSIONS: Many factors (psychosocial, behavioral, hormonal, and
      anatomical) influence weight loss after LRYGB. Although we are uncertain of the
      mechanism, patients with normal initial pouch emptying tend to lose more weight
      than patients who initially exhibit slow or no emptying of the gastric pouch.

PMID- 18806947
TI  - TCF7L2 expression in diabetic patients undergoing bariatric surgery.
AB  - INTRODUCTION: The cause of diabetes in morbidly obese patients is multifactorial,
      including genetic, social, and dietary components. Transcription factor 7-like 2
      (TCF7L2) is a gene that is related to the development of diabetes. This pilot
      study examines TCF7L2 expression in liver samples obtained from morbidly obese
      patients undergoing bariatric surgery. TCF7L2 expression is compared between
      diabetic and nondiabetic patients. METHODS: Liver samples were obtained from 20
      morbidly obese patients undergoing bariatric surgery. Samples were flash frozen
      in liquid nitrogen. Total RNA was extracted from tissue samples using the TRIzol
      reagent (Invitrogen Inc, Carlsbad, CA). Using the iScript cDNA synthesis kit (Bio
      Rad Laboratories, Hercules,CA), cDNA was synthesized. Quantitative polymerase
      chain reaction (qPCR) was done using SYBR Green qPCR Reagents (Stratagene, Cedar
      Creek TX) and the 7300 Real-Time PCR system (Applied Biosystems, Foster City CA).
      Preoperative demographic and gene expression data were correlated using
      univariate analysis and logistic regression models. Only associations with a p
      value less than 0.05 were considered significant. RESULTS: For the entire group,
      there was no correlation between body mass index (BMI) and TCF7L2 expression. In
      morbidly obese nondiabetic patients, there was a positive correlation between
      TCF7L2 expression and BMI (R(2)=0.21). In morbidly obese diabetic patients, there
      was an inverse correlation between TCF7L2 expression and BMI (R(2)=0.58). There
      was no significant relationship between TCF7L2 expression and age or glycosylated
      hemoglobin (HbA1c). CONCLUSIONS: The cause of diabetes is multifactorial but the
      data from our pilot study documents the relationship of TCF7L2 with type 2
      diabetes in morbidly obese patients.

PMID- 18806948
TI  - Effects of endotoxin derived from Escherichia coli lipopolysaccharide on the
      pharmacokinetics of drugs.
AB  - Lipopolysaccharide (LPS) endotoxin is an active component in the outer membrane
      of Gram-negative bacteria. LPS is usually used as an animal model of chronic
      inflammation such as sepsis. During inflammation, development of diarrhea, and
      changes in the plasma protein bindings, in the hepatic and/or intestinal
      microsomal cytochrome P450 (CYP) isozymes, and in the renal excretion of drugs
      have been reported. Thus, in rats pretreated with lipopolysaccharide endotoxin
      isolated from Escherichia Coli (ECLPS rats), the absorption, the distribution,
      the metabolism, and the excretion of drugs could be expected to alter.
      Interestingly, in ECLPS rats, the time-dependent effects on the hepatic CYP
      isozymes have been reported. Thus, in ECLPS rats, the pharmacokinetics of drugs
      which are mainly metabolized via hepatic CYP isozymes could be expected to be
      time-dependent. In this review, an attempt to explain changes in the
      pharmacokinetics of drugs reported in the literature was made in terms of hepatic
      CYP isozyme changes or urinary excretion changes in ECLPS rats.

PMID- 18806949
TI  - 2,2-dimethyl-2H-pyran-derived alkaloids I. Practical synthesis of acronycine and
      benzo[b]acronycine and their biological properties.
AB  - The 2,2-dimethyl-2H-pyran-derived alkaloids acronycine and its demethylated
      congeners were prepared in three steps from anthranilic acid and phloroglucinol.
      The phenylboronic acid-mediated interamolecular cyclization reaction of 1,3
      dihydroxyacridone and 3-methylbut-2-enal was employed as a key step, which was
      also applied to the synthesis of related cytotoxic benzo[b]acronycine. Inhibitory
      activities of the compounds prepared on topoisomerase I and II as well as their
      cytotoxicities were evaluated. Cytotoxicity of 2 is closely related to the strong
      inhibitory activity against topo II at 20 microM level.

PMID- 18806950
TI  - Chemical constituents from the flower of Datura metel L.
AB  - Phytochemical investigation of the 50% ethanol eluate fraction of macroporous
      resin for the flower of Datura metel L. led to the isolation of a new compound
      named yangjinhualine A (1) and five known megastigmane sesquiterpenes through
      repeated silica gel and ODS column chromatography and semipreparative HPLC. The
      structures of these compounds were determined by spectroscopic methods, including
      2D-NMR, ESI-MS, and HR-ESI-MS spectrometry as well as by comparison with
      published data. Five known megastigmane sesquiterpenes were also isolated from D.
      metel L. for the first time.

PMID- 18806951
TI  - Neuroprotective effect of benzylideneacetophenone derivative on the MPTP model of
      neurodegeneration in mice.
AB  - In this study, we investigated the neuroprotective effect of a
      benzylideneacetophenone derivative, JC3, in a mouse model of 1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD). C57BL/6 mice
      were treated with MPTP (30 mg/kg, i.p.) for 5 consecutive days. JC3 (10 mg/kg,
      i.p.) treatment was initiated 2 h after the first administration of MPTP and then
      at 24-h intervals for 3 consecutive days. The mice were sacrificed for analyses 7
      days after the last MPTP injection. Immunohistochemistry and Western blot were
      used to determine the expression levels of tyrosine hydroxylase (TH), dopamine
      transporter (DAT), OX-42 (a marker of microglial activation), and glial
      fibrillary acid protein (GFAP, a marker of astrocyte activation) in the
      substantia nigra (SN) and striatum (ST). The results of these experiments
      demonstrated that JC3 restored the decreased TH-immunoreactivity (IR) and DAT and
      JC3 attenuated the increase in OX-42, GFAP, and COX-2 on the SN and ST on day 7
      post-MPTP injection. These results suggest that JC3 can be a neuroprotective
      agent in an MPTP-induced model of PD.

PMID- 18806952
TI  - GPR12 selections of the metabolites from an endophytic Streptomyces sp.
      associated with Cistanches deserticola.
AB  - An endophytic Streptomyces sp. (AC-2) was isolated from the root of Cistanches
      deserticola Y.C.Ma.. Chemical investigations of the culture broth of AC-2
      afforded fifteen compounds including K1115 A (1), tyrosol (2), phenylethylamine
      derivatives (3, 4), cyclic dipeptides (5-8), nucleosides and their aglycones (9
      13), N-acetyltryptamine (14), and pyrrole-2-carboxylic acid (15). Only tyrosol
      can promote an increase of intracellular cAMP special on GPR12 transfected cells,
      such as CHO and HEK293, which means it may be a possible ligand for GPR12.

PMID- 18806953
TI  - Daidzein modulates induction of hepatic CYP1A1, 1B1, and AhR by 7,12
      dimethylbenz[a]anthracene in mice.
AB  - We investigated the hepatic effects of daidzein on the 7,12
      dimethylbenz(a)anthracene (DMBA)-induced enzymatic activity and expression of
      CYP1A1 and CYP1B1 in mice. Daidzein was administered orally to mice at 5 or 25
      mg/kg BW for three weeks, after which DMBA (34 mg/kg BW) was administered
      intragastrically twice a week for two weeks. Twenty-four hours after the last
      DMBA treatment, the mice were sacrificed. DMBA induced CYP1 activity as well as
      the expression of CYP1A1 and CYP1B1. The catalytic activity of CYP1 enzymes was
      determined as 7-ethoxyresorufin-O-deethylase (EROD) activity. Each of these
      effects was significantly reduced by daidzein; however, the reduction was more
      pronounced for CYP1A1. Daidzein also exerted a negative effect on the
      transcription of CYP1A1 by AhR, similar to its effect on CYP1A1. The AhR
      dependent inhibition of CYP1 by daidzein may explain the anticancer effects of
      daidzein.

PMID- 18806954
TI  - Identification of ssDNA aptamers specific for anti-neuroexcitation peptide III
      and molecular modeling studies: insights into structural interactions.
AB  - Twelve ssDNA aptamers specific for a novel recombinant anti-neuroexcitation
      peptide (ANEPIII) were identified using the SELEX method from a 79-nucleotide
      ssDNA pool to purify ANEPIII in a more efficient way. To further understand the
      binding modes between ssDNA and ANEPIII, fully flexible dinucleotides were docked
      onto the homology-modeled ANEPIII structure. AutoDocking identified favorable
      binding sites on ANEPIII for nucleotides, which was valuable for designing more
      potent ligands.

PMID- 18806955
TI  - Affinity-purification of fibrinogenase with high proteolytic activity from
      Agkistrodon halys (Chinese) Venom.
AB  - To purify and characterize the fibrinogenase with high proteolytic activity from
      Agkistrodon halys (Chinese) Venom. Monoclonal antibodies against fibrinogenase
      were prepared and a novel affinity chromatography equipped with a monoclonal
      antibody against fibrinogenase was developed and applied for the purification of
      fibrinogenases. The purified fibrinogenase was identified by fibrinolytic
      activity assay, and antithrombosis activity assay. HPLC chromatography and SDS
      PAGE analysis demonstrated the uniformity and purity of the purified
      fibrinogenase. In comparison with a conventional A-50 chromatography method,
      affinity-purified fibrinogenase showed higher activity (3631 U mg(-1) vs 501 U
      mg(-1)). In addition, the physiological activity of the fibrinogenase both in
      vitro and ex vivo showed the purified fibrinogenase can specifically degrade beta
      , gamma-fibrinogen and has a high anti-thrombotic activity. In conclusion, the
      purified fibrinogenase by affinity column were shown to be homogeneous and showed
      a high and specific proteolytic activity against beta-chains of fibrinogen
      molecules and antithrombosis activity.

PMID- 18806956
TI  - Structurally related cytotoxic effects of flavonoids on human cancer cells in
      vitro.
AB  - Flavonoids exist extensively in the human diet, and a variety of health effects
      have been ascribed to them. The cytotoxic effects of 23 flavonoids on breast
      cancer cells (MDA-MB-231 and MCF-7), colorectal carcinoma cells (LoVo and DLD-1)
      and prostatic cancer cells (PC3) were investigated. By comparing the cytotoxicity
      (EC(50)) of selected molecules that differ in only one structure element, we
      identified several structural properties associated with enhanced cytotoxicity,
      including the presence of the 2,3-double bond, appropriate hydroxyl numbers, 3
      OH, 6-OH and ortho-hydroxylation in ring B. Flavonoids with a 5-OH exhibited
      lower cytotoxicity than their non-hydroxylated counterparts. Results indicated
      that 3,6-dihydroxylflavone showed the most potent cytotoxic effect on these
      cancer cells. The appearance of apoptotic cells with DAPI staining was observed
      in cancer cells under 3,6-dihydroxylflavone treatment, and the apoptosis analysis
      by flow cytometry also showed that 3,6-dihydroxylflavone induced apoptotic cell
      death in these cancer cells. These results revealed the structurally related
      toxicity of flavonoids on human cancer cells, and indicates that 3,6
      dihydroxylflavone is an active compound worthy of development for cancer
      chemotherapy.

PMID- 18806957
TI  - Structure activity relationship studies of anti-inflammatory TMMC derivatives: 4
      dimethylamino group on the B ring responsible for lowering the potency.
AB  - We previously synthesized 2',4',6'-tris(methoxymethoxy)chalcone (TMMC)
      derivatives with various substituents on the A ring that showed potent anti
      inflammatory effects by inhibiting NO production in RAW 264.7 cells. The 2'
      hydroxy group on the A ring could elevate the electrophilicity of Michael
      addition of GSH and electron donating groups on the A ring could stabilize the
      GSH adduct by decreasing the acidity of the alpha-hydrogen. Using this
      interpretation, we tested various substituents on the B ring and established a
      proper balance between biological activity and the position of the electron
      donating or electron withdrawing groups on the B ring. In this case, the 2'
      hydroxy group was excluded because it could cause the formation of GSSG through a
      phenoxy radical and can confuse the interpretation of the biological results.
      Chalcone derivatives without 2'-hydroxy are likely to deplete cellular GSH levels
      by a Michael addition process. Strong electron donating groups on the B ring,
      such as 4-dimethylamino group, gave the weakest inhibition of NO production. A 4
      dimethyamino group on the B ring could decrease the stability of the GSH adduct
      by weakening the C-S bond strength through movement of an electron pair on
      nitrogen via an aromatic ring.

PMID- 18806958
TI  - Synergistic immunostimulating activity of pidotimod and red ginseng acidic
      polysaccharide against cyclophosphamide-induced immunosuppression.
AB  - We investigated the synergistic effect of combined treatment with red ginseng
      acidic polysaccharide (RGAP) from Panax ginseng C.A. Meyer and pidotimod in
      cyclophosphamide-treated mice. The combination of pidotimod and RGAP restored
      concanavalin A-induced splenic T cell proliferation and LPS-stimulated B cell
      proliferation significantly. The production of nitric oxide from peritoneal
      macrophages was increased by the combinations. NK cell activity was increased by
      RGAP alone or in combination with pidotimod. A synergistic increase in the level
      of serum IL-12 and interferongamm was observed when the combination of the two
      was used. RGAP alone or in combination with pidotimod modulated the level of
      serum C-reactive protein to a near-normal level. These results indicate that
      combinations of pidotimod and RGAP are synergistic and suggest that combination
      therapy using pidotimod and RGAP for improving immune activity may provide an
      additional benefit over the use of the two drugs by themselves.

PMID- 18806959
TI  - Morin protects acute liver damage by carbon tetrachloride (CCl(4)) in rat.
AB  - The purpose of this study was to investigate possible beneficial effects of morin
      on CCl(4)-induced acute hepatotoxicity in rats. Rats received a single dose of
      CCl(4) (150 microL/100 g 1:1 in corn oil). Morin treatment (20 mg/kg) was given
      at 48, 24, and 2 h before CCl(4) administration. CCl(4) challenge elevated serum
      alanine transaminase (ALT), aspartate transaminase (AST), and alkaline
      phosphatase (ALP) levels, but these effects were prevented by the pretreatment of
      rats with morin. To identify the mechanism of protective activity of morin in
      CCl(4)-induced hepatotoxicity in rats, we investigated expressions of tumor
      necrosis factor alpha (TNF-alpha), interleukin-1beta (IL-1beta), interleukin-6
      (IL-6), and inducible nitric oxide (iNOS). The expressions of TNF-alpha, IL
      1beta, IL-6, and iNOS were increased by CCl(4) treatment and increased
      expressions of those were decreased by morin. These findings suggest that morin
      prevents acute liver damage by inhibiting the production of TNF-alpha, IL-1beta,
      IL-6, and iNOS.

PMID- 18806960
TI  - Whitening activity of luteolin related to the inhibition of cAMP pathway in alpha
      MSH-stimulated B16 melanoma cells.
AB  - To examine the possibility of luteolin as a whitening agent, we measured
      antioxidant activity using DPPH assay, NBT/XO assay and intracellular ROS
      scavengning assay and depigmenting activity using tyrosinase assay, alpha-MSH
      induced melanin production in B-16 cells. Luteolin showed dose-dependent anti
      oxidant activity in DPPH, NBT/XO and intracellular ROS assay. Also, luteolin
      directly inhibited xanthine oxidase activity in a dose-dependent manner. Although
      luteolin did not directly inhibit tyrosinase activity, it dose-dependently
      inhibited both tyrosinase activity and melanin production in B16 melanoma cells
      stimulated by 1 microM alpha-MSH. Luteolin dose-dependently inhibited cAMP levels
      in B16 melanoma cells stimulated by 1 microM alpha-MSH and 1 microM forskolin,
      which suggest that luteolin directly inhibits adenyl cyclase in B16 melanoma
      cells. Therefore, these results suggest that whitening activity of luteolin may
      be due to the inhibition of adenyl cyclase involved in the signal pathway of
      alpha-MSH in B16 melanoma cells.

PMID- 18806961
TI  - Continentalic acid from Aralia continentalis induces growth inhibition and
      apoptosis in HepG2 cells.
AB  - In this study, we investigated the effects of continentalic acid (CA, (-)-pimara
      8(14), 15-diene-19-oic acid), a diterpenic acid, isolated from Aralia
      continentalis, on the proliferation and apoptosis induction of HepG2 cells. In 3
      (4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, the
      inhibitory effect became gradually stronger with the passage of time, 24, 48 and
      72 h after treatment with CA, and the most significant effect was observed at 72
      h. CA treatment for 72 h induced DNA fragmentation in a dose-dependent manner.
      Furthermore, flow cytometric analysis of HepG2 cells exposed to CA showed that
      apoptotic cells increased in a dose-dependent manner. The induction of apoptosis
      in HepG2 cells by CA was mediated through the activation of caspase-3, Bak, and
      Bax, and then through the cleavage of peroxisome proliferator-activated receptor
      (PARP) and the down-regulation of Bcl-2. These results demonstrate that CA
      efficiently induces apoptosis and is a good candidate for further evaluation as
      an effective chemotherapeutic agent.

PMID- 18806962
TI  - Butein sensitizes human leukemia cells to apoptosis induced by tumor necrosis
      factor-related apoptosis inducing ligand (TRAIL).
AB  - Resistance to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)
      therapy is frequently encountered, requiring combined treatments with sensitizing
      agents. It is, therefore, important to find nontoxic drugs which can be used
      together with TRAIL. In this study, we investigated natural compounds that can
      overcome resistance to TRAIL, and found that butein, a polyphenol, exhibits
      significant synergism with TRAIL. Treatment with TRAIL in combination with
      subtoxic concentrations of butein sensitizes TRAIL-resistant human leukemia U937
      cells to apoptosis. Butein increased caspase-3 activity and expression of death
      receptor DR5. The apoptotic cell death induced by combined treatment was
      significantly reduced by z-DEVD-fmk, a caspase-3 inhibitor, suggesting a critical
      role of caspase-3 in apoptosis. These results indicate that butein sensitizes
      TRAIL-resistant U937 cells to TRAIL-induced apoptosis in a caspase-3 dependent
      manner which might be correlated with upregulation of death receptor DR5. Our
      data suggests that combined treatment with butein and TRAIL may provide a safe
      and effective strategy for treating cancer.

PMID- 18806963
TI  - High performance liquid chromatographic analysis of rabeprazole in human plasma
      and its pharmacokinetic application.
AB  - A simple and sensitive HPLC method for the analysis of rabeprazole in plasma is
      described using UV detection in the presence of lorazepam as the internal
      standard. Rabeprazole and lorazepam were extracted with ethyl ether and
      quantitated using a reverse-phase C(18) column. The method was specific as there
      were no interfering peaks in the human plasma eluting at the retention times of
      rabeprazole and lorazepam. The method was fully validated in human plasma for the
      concentration range of 20.0-1000.0 ng/ml. The correlation coefficients were
      greater than 0.999. Extraction recoveries were 72.3% for the drug and 79.1% for
      the internal standard. The method was simple, reliable, and accurate for the
      quantitation of rabeprazole in human plasma. The same plasma samples, which were
      collected in healthy male volunteers administered a 20 mg tablet of Pariet, were
      analyzed by HPLC and LC/MS/MS. As a result of that, there was no significant
      difference between pharmacokinetic parameters. The suitability of HPLC method for
      pharmacokinetic studies was verified by determining the relevant pharmacokinetic
      parameters.

PMID- 18806964
TI  - Effect of pioglitazone on the pharmacokinetics of verapamil and its major
      metabolite, norverapamil, in rats.
AB  - Pioglitazone, a thiazolidinedione antidiabetic drug, inhibits cytochrome P450
      (CYP) 2C8 and CYP3A4 enzymes in vitro. This study investigated the effect of
      pioglitazone on the pharmacokinetics of verapamil and its major metabolite,
      norverapamil, in rats, after oral administration of verapamil (9 mg/kg) in the
      presence or absence of pioglitazone (0.3 or 1.0 mg/kg). Pioglitazone altered
      verapamil pharmacokinetics compared with verapamil alone. The presence of 1.0
      mg/kg of pioglitazone significantly (p < 0.05) increased the area under the
      plasma concentration-time curve (AUC) and the peak concentration (C(max)) of
      verapamil by 49.0% and 46.8%, respectively, and significantly (p < 0.05)
      decreased the total plasma clearance (CL/F) of verapamil by 32.8%. The metabolite
      parent AUC ratio in the presence of pioglitazone (1.0 mg/kg) significantly (p <
      0.05) decreased by 21.9% compared to the control group. Thus, coadministration of
      pioglitazone inhibited the CYP3A4-mediated metabolism of verapamil.

PMID- 18806965
TI  - Hydrophilic interaction chromatography-tandem mass spectrometry of donepezil in
      human plasma: application to a pharmacokinetic study of donepezil in volunteers.
AB  - A selective, sensitive and rapid hydrophilic interaction liquid chromatography
      with electrospray ionization tandem mass spectrometry was developed for the
      determination of donepezil in human plasma. Donepezil was twice extracted from
      human plasma using methyl tert-butyl ether at basic pH. The analytes were
      separated on an Atlantis HILIC Silica column with the mobile phase of
      acetonitrile: ammonium formate (50 mM, pH 4.0) (85:15, v/v) and detected by
      tandem mass spectrometry in the selective reaction monitoring mode. The
      calibration curve was linear (r = 0.9994) over the concentration range of 0.10
      50.0 ng/mL and the lower limit of quantification was 0.1 ng/mL using 200 muL
      plasma sample. The coefficient of variation and relative error for intra-and
      inter-assay at four QC levels were 2.7 to 10.5% and -10.0 to 0.0%, respectively.
      There was no matrix effect for donepezil and cisapride. The present method was
      successfully applied to the pharmacokinetic study of donepezil after oral dose of
      donepezil hydrochloride (10 mg tablet) to male healthy volunteers.

PMID- 18806966
TI  - Arterial compliance and vitamin E blood levels with a self emulsifying
      preparation of tocotrienol rich vitamin E.
AB  - The tocotrienol vitamin E has potent antioxidant property, however absorption is
      low due to high lipid solubility. A self emulsifying preparation of tocotrienol
      rich vitamin E (SF-TRE) had been reported to increase their bioavailability. This
      randomized, placebo controlled, blinded end point clinical study aimed to
      determine the effects of 50, 100 and 200 mg daily of SF-TRE and placebo for two
      months on arterial compliance and vitamin E blood levels. Assessment of arterial
      compliance by carotid femoral pulse wave velocity (PWV) and augmentation index
      (AI), plasma vitamin E, serum total cholesterol and low density lipoprotein
      cholesterol were taken before and after 2 months' treatment in 36 healthy males.
      Un-supplemented tocotrienol levels were low, after treatment, all SF-TRE treated
      groups had significantly higher plasma alpha, delta and delta tocotrienol
      concentrations compared to placebo. Augmentation index change from baseline to
      end of treatment for groups placebo, 50, 100, and 200 mg were 2.22+/-1.54, 
      6.59+/-2.84, -8.72+/-3.77, and -6.27+/-2.67% respectively (p=0.049, 0.049, and
      0.047 respectively). Groups 100 and 200 mg showed significant improvement after
      treatment with pulse wave velocity reductions of 0.77 m/s and 0.65 m/s
      respectively (p=0.007 and p=0.002). There was no effect of SF-TRE on serum
      lipids. We conclude that there was a trend towards improvement in arterial
      compliance with 2 months' of SF-TRE.

PMID- 18806967
TI  - Determination of enantiomeric impurity of etodolac by capillary electrophoresis
      using (2-hydroxypropyl)-beta-cyclodextrin.
AB  - A capillary electrophoresis method was developed to determine the impurity of
      etodolac enantiomers. (2-Hydroxypropyl)-beta-cyclodextrin (HP-beta-CD) was used
      as a chiral selector and ketoprofen as an internal standard to improve the peak
      area precision. The seperation of the etodolac enantiomers was achived within 35
      min at 15 degrees C and its highest resolution was about 4.0 using phosphate
      buffer (0.1 M, pH 6.0) with 15 mM HP-beta-CD and UV detection at 225 nm with a
      reference wavelength at 360 nm. This method allowed determination of 0.2% of (R)
      (-)-etodolac in (S)-(+)-etodolac and method validation showed adequate linearity
      over the required range.

PMID- 18806968
TI  - [Tuberous sclerosis: diagnostic criteria and new treatment approaches].
AB  - With a prevalence of 1 in 6,000 births, tuberous sclerosis is a relatively
      frequent hamartoma and tumor syndrome inherited as an autosomal dominant trait,
      which manifests primarily on the skin and in the central nervous system. Decisive
      factors for morbidity and mortality and thus for the prognosis are the changes in
      the central nervous system in the form of cortical hamartomas. Treatment for many
      years consisted solely in using nonspecific symptomatic approaches;
      dermatological therapy comprised mainly laser or electroacoustic ablation of
      facial angiofibromas. New models of therapy hinder the pathogenesis of tuberous
      sclerosis. Various studies provided evidence that the macrolide rapamycin
      decreases growth of brain and kidney tumors by specific inhibition of mTOR
      kinase. Synergistic effects were observed in combination therapy with the
      cytokine IFN-gamma.

PMID- 18806969
TI  - [Unusual combination of clinical forms in a young man. Atypical pityriasis
      rosea].
AB  - Uncommon forms of pityriasis rosea (PR) are found in a not inconsiderable
      proportion of patients (totaling approximately 20%) and predominantly affect
      children and young adults. They are characterized by atypical morphology and
      distribution of the primary medallion or also of the subsequent exanthematous
      individual lesions. The etiology of PR is not yet known. It is possible that the
      underlying cause of PR is viral in origin.

PMID- 18806970
TI  - [Reticular erythematous plaques].
AB  - Reticular erythematous mucinosis (REM) syndrome primarily affects young women;
      the skin lesions usually appear on the chest and upper back. REM is diagnosed on
      the basis of the clinical picture and histological findings. REM syndrome is
      often associated with lupus erythematosus tumidus. Both diseases respond well to
      treatment with chloroquin. Topical tacrolimus and the use of a pulsed dye laser
      have fewer side effects and have also proved to be effective.

PMID- 18806971
TI  - [Vestibular nerve: modern diagnostic and new treatment options].

PMID- 18806972
TI  - [Forced sterilisation of the hereditary deaf in the Third Reich : Its reflection
      in the scientific ENT literature.]
AB  - BACKGROUND: The Law for the Prevention of Genetically Diseased Offspring (enacted
      in Germany in 1934 and in Austria in 1940) allowed the forced sterilisation of
      people with hereditary disorders, including hereditary deafness. Doctors were
      required to register their patients who qualified under the Law and to cooperate
      in establishing the diagnosis. METHOD: This study investigated how the questions
      and problems related to this topic were discussed in three German-language
      scientific ENT journals published between 1934 and 1944. RESULTS AND DISCUSSION:
      A few ENT specialists appeared as "protagonists" of the eugenics programme and
      supported its implementation. Others seemed to be "sceptics" of the programme
      who, though not overtly objecting to it, warned against its uncritical
      application. The scientific discussion was nevertheless objective and not
      distorted by ideological motives. Apparently, the "sceptics" were influential
      enough to widely establish a restrictive practice of diagnosing hereditary
      deafness. Nevertheless, the physicians failed to comply with their professional
      obligation to advocate the welfare of the patient rather than that of "the
      nation".

PMID- 18806973
TI  - [Modern rehabilitation for vestibular disorders using neurofeedback training
      procedures].
AB  - The conservative therapy of long-lasting vestibular disorders has been changed
      over the last few years by the introduction of neuro(bio-)feedback procedures. A
      technical neurofeedback system applies an additional (acoustic, galvanic,
      vibrotactile) stimulus to the patient while performing vestibular exercises. This
      stimulus is dependent on the extent of postural deviation of the patient from a
      normal (ideal) position in space. The neurofeedback system is body worn and
      continuously registers any postural deviation from the normal position so that it
      can apply suitable stimuli to the patient. This new way of rehabilitating
      patients with vertigo seems to be a promising addition in the therapy of long
      lasting, complex vestibular disorders as recent studies have demonstrated.

PMID- 18806974
TI  - [The risk of damaging the round window by CO2 laser myringotomy. A morphological
      experimental analysis of 61 human petrous bone specimens].
AB  - INTRODUCTION: In CO2 laser myringotomy, a self-healing perforation is typically
      created in the lower anterior quadrant. A prominent anterior meatal wall may
      cover that quadrant and necessitate dorsal perforation of the eardrum. This study
      orientationally assessed the risk of damaging the round window membrane (RWM)
      when applying the laser in dorsal eardrum areas. MATERIALS AND METHODS: The round
      window was exposed by otomicrosurgery in 61 human petrous bone specimens. CO2
      laser myringotomy was previously performed with twice the standard power (25 W,
      180 ms, 2.2 mm) in the lower posterior quadrants of 25 specimens, the beam being
      applied directly to the round window niche in five specimens, and the effect of
      the laser radiation was documented. The RWM was subsequently exposed in all
      petrous bones, and the angle correlation of the membrane to the direction of the
      laser beam was digitally measured. RESULTS: The laser did not damage the membrane
      of the round window in any of the cases. The angle between the RWM and the
      external auditory meatus was below 30 degrees in 97% of the petrous bones and
      thus had a nearly parallel course. CONCLUSION: Localization of the window
      caudodorsal to the meatal wall, bone overhanging the membrane, mucosal
      duplications, and membrane alignment nearly parallel to the laser beam make it
      virtually impossible to reach this membranous structure with the CO2 laser.

PMID- 18806975
TI  - [Progredient intracranial bleeding after traumatic brain injury. When is a
      control CCT necessary?].
AB  - BACKGROUND: The aim of the study was to quantify the occurrence of progressive
      intracranial bleeding (PIB) and to identify concomitant parameters in patients
      suffering from traumatic brain injury (TBI). METHODS: TBI patients were included
      if initial and serial cranial computed tomography (CCT) scans were conducted
      within 24 h after trauma. A progression of > or =25% was considered as PIB.
      Patients with progression were compared to those with constant bleeding regarding
      clinical parameters, time lapse and coagulation status. RESULTS: A total of 98
      patients with TBI and intracranial hemorrhaging were analyzed. PIB was detected
      in 45 patients showing significantly more intracerebral bleeding as well as
      fractures to the skull (p<0.05), compared to patients with constant bleeding. No
      significant differences between the groups regarding demographic and clinical
      parameters, time interval between trauma and initial CCT, and coagulation status
      were found. CONCLUSIONS: Early progression of intracranial hemorrhaging occurs in
      nearly every second TBI patient and is recognized frequently in cerebral
      contusions and after fractures to the skull. Hence, early repeated CT scanning is
      indicated in all TBI patients suffering from intracranial bleeding.

PMID- 18806976
TI  - [Functional reconstruction after compartment syndrome of the forearm and hand].
AB  - Ischemic muscle contracture after a compartment syndrome of the forearm and hand
      may result in severe loss of function. In addition to the established muscle
      contracture, a loss of nerve and vessel function can often be found. The clinical
      appearance depends on the involved muscles respectively compartments. Even though
      each case requires individual analysis of the clinical situation, the combination
      of Tsuge's classification with Holden's classification provides a more or less
      systematic approach to treatment that can be adapted to each case according to
      the severity of the contracture of the joints and muscles, the degree of nerve
      and vessel damage, the function of the remaining muscles and nerves, and the
      availability of other functioning muscles for reconstruction.

PMID- 18806977
TI  - [Reconstruction after compartment syndrome].

PMID- 18806978
TI  - [Intense language training for aphasia. Contribution of cognitive factors].
AB  - The best predictor of successful language therapy after stroke is a high
      intensity of treatment (with 5-10 h training per week). However, the necessity of
      several hours of language exercises each day draws considerably on attentional
      and cognitive resources of the patients. Thus, not all aphasic patients may be
      equally suited for intense training approaches. In the present review non-verbal
      cognitive deficits that often accompany a stroke-induced aphasia are described.
      Furthermore, initial empirical data on cognitive functions, which predict the
      success of therapy (intense) after stroke, are summarized. Patients in the acute
      stage benefit most from intense aphasia treatment, when long-term memory
      consolidation is relatively preserved. For the chronic stage, indirect evidence
      suggests that premorbid intelligence as well as attentional functions have
      positive effects on the success of intense therapy. An empirically based
      allocation of patients to intense aphasia treatment awaits the results of
      multicenter trials with sufficiently large sample sizes.

PMID- 18806979
TI  - [Prevention : from the study to the individual].

PMID- 18806980
TI  - [Psychological consequences of patient assaults on mental health staff.
      Prospective and retrospective data].
AB  - BACKGROUND: Psychological consequences of patient assaults on staff members have
      rarely been examined with instruments established for post-traumatic stress
      disorder (PTSD) research. In prior studies, self-defined questionnaires and
      outcomes were used instead. METHODS: We conducted two studies, one prospective
      study with two follow-ups and one retrospective. Forty-six and 88 mental health
      care workers were interviewed, respectively, for psychological consequences after
      a patient assault. Validated instruments from post-traumatic stress disorder
      (PTSD) research were used (PCL-C, IES-R). RESULTS: In the first weeks following
      patient assault, 17% of respondents of the prospective study fulfilled the
      diagnostic criteria for PTSD according to DSM-IV. After further 2 and 6 months in
      the respective studies, the PTSD rates had decreased to 11%. In the retrospective
      study 3% of respondents still had a PTSD diagnosis on average 1.5 years after the
      assault. CONCLUSIONS: Patient assaults can cause PTSD in staff members of mental
      health institutions. Institutions need to organise adequate care for their staff
      affected by assault.

PMID- 18806981
TI  - [Sadistic fetishism--deadly passion. Forensic psychiatric assessment of sex
      offenders].
AB  - This article reviews current developments in psychiatric assessment of sex
      offenders for criminal courts. These developments are characterized by constantly
      changing laws and increasing neurobiological findings about paraphilias.
      Psychiatrists must prepare their reports taking into account the tension between
      psychopathological, neurobiological, and normative aspects of their judgement.
      The complexity of such assessments can best be demonstrated by narratives. This
      narrative concerns a 47-year-old patient who killed eight women after strangling
      them and masturbating or having intercourse with the unconscious victims. He
      explained in detail six of these crimes and gave ample information about his
      history, sexual development, fantasies, and a number of other sexual crimes he
      had committed. From this information a plausible explanation of his development
      to sexual fetishism and from there to sadism could be derived. Brain MRI
      displayed gliotic scars in the frontal lobe and right hippocampus. Consequences
      of the various findings on psychiatric assessment of legal culpability are
      discussed in this paper, concluding that a differentiated approach to the
      assessment is possible only from a psychopathological point of view in which
      behaviour, clinical features, and motivations are analysed.

PMID- 18806982
TI  - [Stroke prevention outside the pharmacy : risk factors and lifestyle].
AB  - Advice on modifiable risk and lifestyle factors for stroke prevention should be
      an established component of medical consultation. It is most important to explain
      that alterations to the lifestyle can be highly efficient with respect to the
      individual risk profile. The following review describes the importance of
      lifestyle factors such as nutrition, smoking, alcohol consumption, psychiatric
      condition, sport, dental hygiene and sleep disturbances for the risk of stroke
      using current data. It provides evidence that lifestyle modifications are highly
      effective with respect to stroke prevention. Corresponding recommendations and
      preventive strategies are presented.

PMID- 18806983
TI  - [Intracranial aneurysm, arteriovenous malformation, and carotid artery stenosis :
      endovascular prophylactic therapy].
AB  - The treatment of acute cerebrovascular disease plays a prominent role in clinical
      routine. However, prophylactic therapy of cerebrovascular disease including
      endovascular options is becoming more and more important. With particular regard
      to endovascular therapies, this summary deals with the natural course of
      cerebrovascular diseases and different treatment strategies for asymptomatic
      intracranial aneurysms, cerebral arteriovenous malformations, and extracranial
      carotid artery stenoses.

PMID- 18806984
TI  - [Alternatives to beta blockers in preventive migraine treatment].
AB  - Drug prevention of migraine is recommended if more than three attacks occur per
      month, acute drug treatment is insufficient, or very severe attacks with aura are
      the main problem. Besides beta blockers, a variety of substances have proved
      efficacious in migraine prevention. Thus individualised treatment of migraine
      patients is possible. When choosing the appropriate preventive drug, the
      potential side effects are considered. Drugs of first choice, besides beta
      blockers, are flunarizine, valproic acid, and topiramate. Second-choice drugs
      with lower efficacy or less well published evidence include amitriptyline,
      venlafaxine, gabapentin, naproxen, acetylsalicylic acid, butterbur root, vitamin
      B2, and magnesium. Flunarizine or propranolol are recommended for children.

PMID- 18806985
TI  - [Choice of early and escalation treatment options for multiple sclerosis].
AB  - Recent advances in understanding of the immunopathogenesis of multiple sclerosis
      (MS) have led to the development of new treatment options. To date several
      immunomodulatory agents have been licensed for the treatment of relapsing
      remitting MS. However, some debate remains on the optimal time point for
      initiating therapy. While there is general consensus on the benefit of an early
      treatment start, the issues of how to define "early MS" and how to identify
      patients with a "benign" disease course have not yet been finally addressed.
      Further open questions include the situations of treatment failure and
      therapeutic escalation. Here we summarize available data from studies on early
      treatment with immunomodulatory drugs for a first demyelinating event, also
      referred to as clinically isolated syndrome. Furthermore, options for the
      escalation of immunomodulatory therapy will be discussed, e.g. with the recently
      licensed monoclonal antibody natalizumab.

PMID- 18806986
TI  - [Volumetry of metastases from renal cell carcinoma: comparison with the RECIST
      criteria].
AB  - For patients with metastasized renal cell carcinoma (RCC), imaging techniques are
      of great importance. Currently, therapy widely relies on antiangiogenic factors,
      which frequently lead to relatively subtle changes in the size of lesions. From
      this aspect the commonly used RECIST criteria (response evaluation criteria in
      solid tumors) must be considered as imprecise for the evaluation of the response
      to therapy. This article gives a review on new software-based volumetric methods,
      which allow therapy-induced changes in the size of metastases from RCC to be
      detected with higher sensitivity and reproducibility. A comparison of RECIST and
      volumetry was carried out with data from patients with metastasized RCC to
      demonstrate the higher sensitivity of the 3D volumetric procedure.

PMID- 18806987
TI  - [Stent-assisted angioplasty for atherosclerotic stenosis of the carotid artery.
      An overview].
AB  - For symptomatic stenosis of the carotid artery the invasive options for treatment
      (by means of stent or operation) are superior to conservative medical treatment.
      Recent multi-center randomized controlled trials, which will be presented here,
      indicate that stenting in the treatment of symptomatic carotid stenosis is
      neither safer nor more effective than carotid endarterectomy. When carried out by
      an experienced interventionalist stent-assisted angioplasty (CAS) is an
      alternative to carotid endarterectomy. Subgroup-analysis indicates that for
      patients older than 70 years of age invasive techniques should be the method of
      choice. In the case of contralateral high-grade stenosis or occlusion, CAS is the
      method of choice. For patients treated by stenting, the periprocedural
      complication rate is not influenced by the use of protection systems. The present
      results on symptomatic carotid stenosis should not be transferred to the therapy
      of asymptomatic carotid stenosis. A 3-armed study (SPACE2) on the comparison of
      the best medical treatment with the invasive treatment modalities (CAS or CEA) is
      in preparation and will be started in 2 months.

PMID- 18806988
TI  - [Peripheral arterial disease. Diagnosis and therapy according to current
      guidelines].
AB  - Guidelines conduce to establish consistent standards of therapy and contribute to
      the orientation and safeguard of the attending physician. Peripheral arterial
      disease (PAD) may be classified according to its stage as intermittent
      claudication, chronic critical limb ischemia or acute limb ischemia. Since these
      diseases are common and life-threatening, current guidelines are of major
      interest for the attending physician, not least because of forensic reasons. This
      overview describes the current principles of diagnosis and therapy as well as
      recent developments in peripheral endovascular intervention. Current national and
      international guidelines, particularly the Transatlantic Intersociety Consensus
      (TASC), were taken into account.

PMID- 18806989
TI  - [Importance of imaging diagnostics and interventional therapy for diseases of the
      lacrimal drainage canals].
AB  - Epiphora (continuous watering of the eyes) is frequently caused by obstruction of
      the lacrimal draining system. Radiographic imaging of the tear ducts after
      contrast injection with the DSA (digital subtraction angiography)
      dacryocystography technique is still the gold standard in patients with severe
      epiphora which does not respond to conservative therapy. Recent techniques, such
      as 3D rotational dacryocystography, MRI and CT are able to show the anatomic
      surroundings in addition to the ductal structures and are especially useful for
      planning endoscopic operations. Dacryocystographically assisted interventions,
      such as balloon dilatation or stenting of tear duct stenoses are technically
      feasible. Balloon dacryocystoplasty is especially successful in patients with
      incomplete or short distance obstructions of the nasolacrimal duct. Stenting may
      improve procedural success and patency rates. Minimally invasive interventional
      therapy is useful as an initial treatment in selected cases, however, long-term
      success rates may be limited and operative dacryocystorhinostomy still plays an
      important role. Comparative studies for evaluation of different therapeutic
      options are necessary.

PMID- 18806990
TI  - [Urethral duplication: long-term results for a rare urethral anomaly].
AB  - INTRODUCTION: Urethral duplication is a rare anomaly that can occur in various
      forms. Urethral duplication must be diagnosed and adequately treated. Only if
      clinical complaints develop should surgical management be considered. PATIENTS
      AND METHODS: The aim of this study was to retrospectively analyze patients with
      congenital urethral duplication: age at the time of diagnosis, type of urethral
      duplication, diagnostic and therapeutic measures as well as clinical aftercare
      were evaluated. RESULTS: This homogeneous and selected cohort included nine male
      children. The average follow-up was 6.2 years. Seven children were symptomatic
      (77.7%). We found a double urethra with epispadias in four boys and with
      hypospadias in three boys and urethral duplication with perineal/anal meatus in
      one patient and normotopia in another patient. In two children without symptoms,
      the urethral duplication was an incidental finding during diagnostic work-up for
      other anomalies. Seven children had additional urological anomalies: one fusiform
      megalourethra, three urethral valves with hypospadias, and two epispadias. Two
      children without symptoms were managed conservatively. An open operation joining
      the urethras was performed in three children, and four boys underwent endoscopic
      treatment of the urethral duplication. Long-term results revealed normal
      continence in all of the children. One child exhibited recurrent urinary tract
      infections and late stricture, which was opened endoscopically in a second
      session. CONCLUSION: A surgical approach is only indicated in the presence of
      clinical complaints. There is no surgical gold standard. The decision is
      ultimately reached on an individual basis depending on the findings and anatomy
      in view of the rarity and variability of the clinical picture. The functional
      result is of foremost importance for the urethra that requires reconstruction,
      but the cosmetic aspect should be respected to the same extent. We present the
      results of our experience in treating children with this urological condition. At
      the same time larger (multicenter) studies are needed, which will make it
      possible to formulate guidelines for this rare anomaly.

PMID- 18806991
TI  - [Radical salvage prostatectomy : Treatment of local recurrence of prostate cancer
      after radiotherapy].
AB  - External beam radiation and low- and high-dose interstitial brachytherapy
      represent therapeutic alternatives to radical prostatectomy for organ-confined
      and locally advanced prostate cancer. Local recurrences are described in 5-35% of
      the patients depending on the individual risk profile, and most recurrences are
      detected due to asymptomatic PSA rise only. According to the most recent data,
      recurrences are defined by a PSA increase >2 ng/ml above the post-radiation
      nadir. Radical salvage prostatectomy represents a secondary local treatment with
      curative intent in patients with organ-confined recurrences. Preoperative risk
      factors predicting organ-confined disease are initial LDR brachytherapy,
      preoperative Gleason biopsy score < or =6, < or =50% biopsy cores involved with
      cancer, and a PSA doubling time >12 months. Metastatic disease should be ruled
      out preoperatively by skeletal scintigraphy, computed tomography, or magnetic
      resonance imaging of the abdomen and the small pelvis, and/or choline PET/CT.
      Functionality of the lower urinary tract is evaluated by urethrocystoscopy and
      urodynamics. The most appropriate candidates for radical salvage prostatectomy
      are patients with organ-confined disease or those with symptomatic local
      recurrences. In experienced hands, morbidity is low with a continence rate of 83
      96% depending on the type of previous radiation therapy. Long-term oncological
      control can be achieved in more than 80% of the patients.

PMID- 18806992
TI  - Bin mapping of genomic and EST-derived SSRs in melon (Cucumis melo L.).
AB  - We report the development of 158 primer pairs flanking SSR motifs in genomic
      (gSSR) and EST (EST-SSR) melon sequences, all yielding polymorphic bands in melon
      germplasm, except one that was polymorphic only in Cucurbita species. A similar
      polymorphism level was found among EST-SSRs and gSSRs, between dimeric and
      trimeric EST-SSRs, and between EST-SSRs placed in the open reading frame or any
      of the 5'- or 3'-untranslated regions. Correlation between SSR length and
      polymorphism was only found for dinucleotide EST-SSRs located within the
      untranslated regions, but not for trinucleotide EST-SSRs. Transferability of EST
      SSRs to Cucurbita species was assayed and 12.7% of the primer pairs amplified at
      least in one species, although only 5.4% were polymorphic. A set of 14 double
      haploid lines from the cross between the cultivar "Piel de Sapo" and the
      accession PI161375 were selected for the bin mapping approach in melon. One
      hundred and twenty-one SSR markers were newly mapped. The position of 46 SSR loci
      was also verified by genotyping the complete population. A final bin-map was
      constructed including 80 RFLPs, 212 SSRs, 3 SNPs and the Nsv locus, distributed
      in 122 bins with an average bin length of 10.2 cM and a maximum bin length of 33
      cM. Map density was 4.2 cM/marker or 5.9 cM/SSR.

PMID- 18806993
TI  - The complex quantitative barley-Rhynchosporium secalis interaction: newly
      identified QTL may represent already known resistance genes.
AB  - Two barley populations, i.e. 135 doubled haploid (DH) lines of the cross 'Igri'
      (rrs1) x 'Triton' (Rrs1) (I x T) and 76 DH lines of the cross 'Post' x 'Vixen'
      (both rrs1) (P x V), were analysed to identify QTL for Rhynchosporium secalis
      resistance independent of the Rrs1 locus by using the single spore R. secalis
      isolate 271 (Rrs1-virulent). A major QTL with its positive allele derived from
      cv. 'Triton' was detected in the I x T population on chromosome 2HS explaining
      almost 80% of the phenotypic variance. Thus, it can be considered as an R-gene
      corresponding to the already described Rrs15(CI8288) on chromosome 2HS. In
      addition, two minor QTL were identified, one in the centromeric region of 6H in a
      highly polymorphic region with already several mapped R-genes and a second one at
      the end of the short arm of chromosome 7H which may be an allele of Rrs2 because
      of its chromosomal position. Regarding the DH population P x V different minor
      QTL were identified on chromosomes 6H and 7H. The first one is corresponding to
      the genomic region of the Rrs13 gene whereas the QTL on chromosome 7H maps in a
      genomic region where several R-genes against different pathogens have been
      localized. A comparison of both QTL analyses reveals no R. secalis isolate 271
      specific resistance locus but leads to the hypothesis that two of the identified
      QTL may be alleles of the R-genes Rrs15(CI8288) and Rrs2.

PMID- 18806994
TI  - Genetic mapping and transcription analyses of resistance gene loci in potato
      using NBS profiling.
AB  - NBS profiling is a method for the identification of resistance gene analog (RGA)
      derived fragments. Here we report the use of NBS profiling for the genome wide
      mapping of RGA loci in potato. NBS profiling analyses on a minimal set of F1
      genotypes of the diploid mapping population previously used to generate the ultra
      dense (UHD) genetic map of potato, allowed us to efficiently map polymorphic RGA
      fragments relative to 10,000 existing AFLP markers. In total, 34 RGA loci were
      mapped, of which only 13 contained RGA sequences homologous to RGAs genetically
      positioned at approximately similar positions in potato or tomato. The remaining
      RGA loci mapped either at approximate chromosomal regions previously shown to
      contain RGAs in potato or tomato without sharing homology to these RGAs, or
      mapped at positions not yet identified as RGA-containing regions. In addition to
      markers representing RGAs with unknown functions, segregating markers were
      detected that were closely linked to four functional R genes that segregate in
      the UHD mapping population. To explore the potential of NBS profiling in RGA
      transcription analyses, RNA isolated from different tissues was used as template
      for NBS profiling. Of all the fragments amplified approximately 15% showed
      putative intensity or absent/present differences between different tissues
      suggesting putative tissue specific RGA or R gene transcription. Putative
      absent/present differences between individuals were also found. In addition to
      being a powerful tool for generating candidate gene markers linked to R gene
      loci, NBS profiling, when applied to cDNA, can be instrumental in identifying
      those members of an R gene cluster that are transcribed, and thus putatively
      functional.

PMID- 18806995
TI  - An association of adverse psychosocial factors with diabetes mellitus: a meta
      analytic review of longitudinal cohort studies.
AB  - AIMS/HYPOTHESIS: There has been substantial interest in the association between
      psychosocial stress and risk of diabetes mellitus, but no data on the systematic
      quantification of the causal relationship have been published. This analysis aims
      to evaluate the association between adverse psychosocial factors and diabetes
      mellitus. METHODS: We performed a search of Medline, PsycINFO, Web of Science and
      PubMed up to July 2008. The studies included were prospective cohort studies
      investigating the association between adverse psychosocial factors and risk of
      diabetes mellitus. RESULTS: There were 22 relationships between psychosocial
      factors and disease-related factors (in 14 papers), of which 16 evaluated the
      associations of adverse psychosocial factors with diabetes control in diabetic
      populations and six evaluated the associations of adverse psychosocial factors
      with the incidence of diabetes in populations without any diagnosed diabetes. The
      overall meta-analysis demonstrated that adverse psychosocial factors were
      significantly associated with poor diabetes control (combined correlation
      coefficient, r = 0.096, p = 0.006), whereas adverse psychosocial factors were not
      associated with incident diabetes mellitus. More notably, sensitivity analyses
      showed that low social support was more robustly associated with poor diabetes
      control than stressful events per se or stress-prone personality or coping style,
      and that adverse psychosocial factors were associated with poor control of type 1
      and type 2 diabetes. CONCLUSIONS/INTERPRETATION: The current review revealed a
      detrimental association of psychosocial factors with the prognosis of both type 1
      and type 2 diabetes. However, any aetiological effect of adverse psychosocial
      factors remains elusive as a result of the small number of individuals enrolled
      in the cohorts studied.

PMID- 18806996
TI  - Changing the glucose cut-off values that define hypoglycaemia has a major effect
      on reported frequencies of hypoglycaemia.
AB  - AIMS/HYPOTHESIS: The aim of this analysis was to quantify the relationship
      between the frequency of hypoglycaemia and various glucose cut-off points for the
      definition of hypoglycaemia, within a range of HbA(1c) strata. METHODS: Data from
      two trials examining insulin glargine dose titration in 12,837 type 2 diabetic
      participants starting insulin therapy were combined. Curves for hypoglycaemia
      frequency plotted against endpoint HbA(1c) level were constructed, using a range
      of glucose cut-off points for hypoglycaemia. RESULTS: During the 12-week study
      period, 3,912 patients recorded 21,592 hypoglycaemic episodes, comprising 242
      severe, 8,871 symptomatic and 12,479 asymptomatic events, corresponding to
      hypoglycaemia event rates of 0.10, 3.8 and 5.3 events per patient year.
      Increasing the hypoglycaemia cut-off point from, for instance, <3.1 to <3.9
      mmol/l more than doubled the percentage of affected patients, e.g. from 17.7 to
      43.3% at HbA(1c) 7.0-7.2%. At higher hypoglycaemia cut-off points the proportion
      of patients having only asymptomatic hypoglycaemia increased, e.g. from 30.7% at
      <3.1 mmol/l to 61.7% of patients at a cut-off point of <3.9 mmol/l. In
      sensitivity analysis, 121 of 1,756 patients with at least one self-monitored
      blood glucose value <3.1 mmol/l experienced severe hypoglycaemia, compared with
      149 of 3,912 patients with a self-monitored blood glucose level of <3.9 mmol/l.
      Thus, to identify 28 more patients with severe hypoglycaemia, the number of
      patients experiencing only non-severe hypoglycaemia more than doubled.
      CONCLUSIONS/INTERPRETATION: The glucose cut-off point defining hypoglycaemia
      greatly affects the reported frequency of hypoglycaemia. When hypoglycaemia is to
      be defined by a predetermined glucose level, to have clinical relevance the cut
      off should be set at a lower level than the threshold of 3.9 mmol/l proposed by
      the American Diabetes Association.

PMID- 18806997
TI  - [Effective pain relief facilitates exercise therapy : Results of a multicenter
      study with controlled-release oxycodone in patients with movement pain].
AB  - BACKGROUND: The efficacy and tolerability of oral controlled-release oxycodone in
      the therapy of musculoskeletal pain were analyzed in this observational study.
      PATIENTS AND METHODS: A total of 843 patients with severe to most severe pain in
      the musculoskeletal system were treated with controlled-released oxycodone for 4
      weeks or up to a maximum of 6 months. Severity of pain, impairment in quality of
      life, and mobility associated with the pain were assessed before and during
      therapy with controlled-release oxycodone by a numerical rating scale (NRS 0-10).
      RESULTS: Pain intensity fell by an average of 65% within the first 4 weeks.
      Physical therapy was practicable in many patients only after implementation of a
      therapy regime with controlled-release oxycodone. Quality of life improved
      significantly under therapy with oxycodone, and the impairment of different
      aspects of life decreased by 50%. CONCLUSION: The therapy of pain of the
      musculoskeletal system with controlled-release oxycodone is efficient. An
      effective pain relief makes physical therapy practicable, reduces the impairment
      in different parts of life, and increases quality of life.

PMID- 18806998
TI  - [Determining the indication for primary total hip and knee replacement. Results
      of external quality assurance of over 270,000 primary total hip and knee
      replacements].
AB  - BACKGROUND: The German mandatory quality assurance programme collects data from
      all primary total hip and knee replacements. The quality of the indication is
      measured by clinical and radiological criteria. The results were analysed in
      terms of differences in establishing the indication subject to patient and
      hospital characteristics. MATERIALS AND METHODS: Data on more than 270,000
      primary total hip and knee replacements that were operated in 2006 in Germany
      were analysed concerning differences in the quality of the indication subject to
      age, gender, hospital volume and density of population and hospitals
      (metropolitan vs rural areas). The statistical analysis was done by exact
      Fisher's test. RESULTS: The quality of the indication was statistically
      significantly better in men, patients 60 and older, in rural areas and in high
      volume hospitals (50 and more joint replacements per year). DISCUSSION: Data of
      this mandatory German quality assurance programme are useful to describe
      differences in medical care. The results are valid and complete. An exact
      analysis of the reasons for these differences is difficult though. Data focus is
      on quality assurance and represent only in-hospital results. CONCLUSION: Further
      analyses are necessary to ascertain whether the differences in quality of care
      are deficits or only variances in medical care.

PMID- 18806999
TI  - [Can failed back surgery be prevented? Psychological risk factors for
      postoperative pain after back surgery].
AB  - Aside from the surgical technique used, the development of peri- and
      postoperative pain and impairments in patients following intervertebral disk
      surgery is also determined to a crucial extent by psychological factors. Based on
      a systematic literature review, we checked whether evidence-based recommendations
      could be deduced on how to take into account psychological risk factors in back
      surgery in order to avoid postoperative complications, such as failed back
      surgery syndrome. The current state of research suggests three groups of risk
      factors: (1) negative psychological factors, (2) preexisting pain chronification,
      and (3) psychological disorders. In the case of elective intervertebral disk
      surgery, these factors should therefore be determined and identified
      preoperatively and taken into account in the indication for surgery. Multimodal
      treatments could conceivably prove to be more effective, or else psychological
      pain management therapy might be considered prior to surgery so as to avoid
      postoperative complications. If surgery is medically unavoidable despite existing
      risk factors, postoperative treatment should incorporate psychological pain
      management therapy at an early stage in the context of a multidisciplinary
      approach.

PMID- 18807000
TI  - [Analgesia in shoulder, elbow and hand surgery].
AB  - Surgery of the shoulder, elbow, and hand can cause considerable pain. According
      to data from randomized controlled trials, local or regional anesthesia is
      recommended for analgesia during and after surgery of the upper extremity. This
      treatment can be supplemented with potent opioids and nonsteroidal anti
      inflammatory drugs in a multimodal analgesia approach. According to a
      metaanalysis of randomized controlled trials, an interscalene block is
      recommended for analgesia during and after surgery of the shoulder. For the elbow
      joint, a peripheral block is also recommended to allow for effective analgesia
      and physiotherapy postoperatively. In addition, cooling and physiotherapeutic
      techniques are beneficial in postoperative management.

PMID- 18807001
TI  - [Organisation of acute pain therapy].
AB  - Orthopaedic and traumatized patients often suffer from severe pain after surgery
      or trauma. Their early recovery also depends on an efficient acute pain relief
      based on a combination of systemic medication, local drug application and
      physical therapy. In 2007, new guidelines for the treatment of perioperative and
      traumatic pain were published. Based on these guidelines standard operating
      procedures for each hospital should be developed and implemented. Courses on
      analgesic concepts should be offered regularly for the involved staff. It is
      helpful to establish an acute pain service for daily rounds and documentation.
      The individual patient should be informed about his specific acute pain therapy
      before the operation. Pain scores should be frequently documented by the patient.

PMID- 18807002
TI  - [Past pains are what I like. Perioperative and postoperative pain management in
      orthopaedic and trauma surgery].

PMID- 18807003
TI  - [Knee and shoulder arthroscopy. Positioning and thermal injuries].
AB  - Intraoperative positioning injuries during shoulder- and knee arthroscopy are
      rare complications and affect mainly nerves and soft tissue. Although the
      majority of these complications are reversible, in some cases serious negative
      consequences for the patient persist. This article describes the frequency of
      several positioning injuries including their prevention and the appropriate
      treatment. The legal responsibilities are illustrated as well as the importance
      of an intense preoperative investigation of preexisting diseases and possible
      risk factors. Furthermore, a review of possible thermal injuries of the patient
      during arthroscopy caused by e.g. electrosurgical instruments or the cold light
      source, is given as well as prevention strategies.

PMID- 18807004
TI  - [Patellofemoral joint: still the poor relative in knee treatment?].

PMID- 18807005
TI  - Titrated safe extubation: application of an original strategy for safe management
      of perioperative glottis edema with severe upper airway obstruction.

PMID- 18807006
TI  - Diabetes mellitus is an independent risk factor for ICU-acquired bloodstream
      infections.
AB  - OBJECTIVE: To investigate the role of diabetes as risk factor for ICU-acquired
      bloodstream infections (BSI). DESIGN: Prospective observational study. SETTING: A
      general eight-bed ICU of a tertiary hospital. PATIENTS: Three hundred and forty
      three consecutive patients (63 diabetic and 280 nondiabetic) admitted in the ICU.
      METHODS: BSI episodes in the ICU were recorded and classified as primary,
      secondary, catheter-related and mixed according to strict criteria. In all
      patients, blood glucose was strictly controlled with a continuous insulin
      infusion within a range of 80-120 mg/dl. RESULTS: One-hundred and eighteen
      patients (34.4%) developed at least one BSI episode. Diabetic patients had an
      increased probability of developing at least one BSI episode compared with
      nondiabetic patients (hazard ratio = 1.66, 95% confidence interval 1.04-2.64, P =
      0.034) in a Cox proportional hazards regression model adjusting for age, gender,
      admission category and APACHE II score at admission in the ICU and comorbidities.
      CONCLUSIONS: Despite strict glycemic control, diabetic patients have a 1.7-fold
      probability of developing an ICU-acquired BSI compared to nondiabetic subjects.

PMID- 18807007
TI  - The influence of a balanced volume replacement concept on inflammation,
      endothelial activation, and kidney integrity in elderly cardiac surgery patients.
AB  - PURPOSE: A balanced fluid replacement strategy appears to be promising for
      correcting hypovolemia. The benefits of a balanced fluid replacement regimen were
      studied in elderly cardiac surgery patients. METHODS: In a randomized clinical
      trial, 50 patients aged >75 years undergoing cardiac surgery received a balanced
      6% HES 130/0.42 plus a balanced crystalloid solution (n = 25) or a non-balanced
      HES in saline plus saline solution (n = 25) to keep pulmonary capillary wedge
      pressure/central venous pressure between 12-14 mmHg. Acid-base status,
      inflammation, endothelial activation (soluble intercellular adhesion molecule-1,
      kidney integrity (kidney-specific proteins glutathione transferase-alpha;
      neutrophil gelatinase-associated lipocalin) were studied after induction of
      anesthesia, 5 h after surgery, 1 and 2 days thereafter. Serum creatinine (sCr)
      was measured approximately 60 days after discharge. RESULTS: A total of 2,750 +/-
      640 mL of balanced and 2,820 +/- 550 mL of unbalanced HES were given until the
      second POD. Base excess (BE) was significantly reduced in the unbalanced (from
      +1.21 +/- 0.3 to -4.39 +/- 1.0 mmol L(-1) 5 h after surgery; P < 0.001) and
      remained unchanged in the balanced group (from 1.04 +/- 0.3 to -0.81 +/- 0.3 mmol
      L(-1) 5 h after surgery). Evolution of the BE was significantly different.
      Inflammatory response and endothelial activation were significantly less
      pronounced in the balanced than the unbalanced group. Concentrations of kidney
      specific proteins after surgery indicated less alterations of kidney integrity in
      the balanced than in the unbalanced group. CONCLUSIONS: A total balanced volume
      replacement strategy including a balanced HES and a balanced crystalloid solution
      resulted in moderate beneficial effects on acid-base status, inflammation,
      endothelial activation, and kidney integrity compared to a conventional
      unbalanced volume replacement regimen.

PMID- 18807008
TI  - Sodium lactate versus mannitol in the treatment of intracranial hypertensive
      episodes in severe traumatic brain-injured patients.
AB  - OBJECTIVES: Traumatic brain injury (TBI) is still a major cause of mortality and
      morbidity. Recent trials have failed to demonstrate a beneficial outcome from
      therapeutic treatments such as corticosteroids, hypothermia and hypertonic
      saline. We investigated the effect of a new hyperosmolar solution based on sodium
      lactate in controlling raised intracranial pressure (ICP). DESIGN AND SETTING:
      Prospective open randomized study in an adult ICU. PATIENTS: Thirty-four patients
      with isolated severe TBI (Glasgow Coma Scale <or= 8) and intracranial
      hypertension were allocated to receive equally hyperosmolar and isovolumic
      therapy, consisting of either mannitol or sodium lactate. Rescue therapy by
      crossover to the alternative treatment was indicated when ICP could not be
      controlled. The primary endpoint was efficacy in lowering ICP after 4 h, with a
      secondary endpoint of the percentage of successfully treated episodes of
      intracranial hypertension. The analysis was performed with both intention-to
      treat and actual treatments provided. MEASUREMENTS AND RESULTS: Compared to
      mannitol, the effect of the lactate solution on ICP was significantly more
      pronounced (7 vs. 4 mmHg, P = 0.016), more prolonged (fourth-hour-ICP decrease: 
      5.9 +/- 1 vs. -3.2 +/- 0.9 mmHg, P = 0.009) and more frequently successful (90.4
      vs. 70.4%, P = 0.053). CONCLUSION: Acute infusion of a sodium lactate-based
      hyperosmolar solution is effective in treating intracranial hypertension
      following traumatic brain injury. This effect is significantly more pronounced
      than that of an equivalent osmotic load of mannitol. Additionally, in this
      specific group of patients, long-term outcome was better in terms of GOS in those
      receiving as compared to mannitol. Larger trials are warranted to confirm our
      findings.

PMID- 18807009
TI  - Mortality in acute cardiogenic pulmonary edema treated with continuous positive
      airway pressure.
AB  - OBJECTIVE: To investigate mortality in acute cardiogenic pulmonary edema (ACPE)
      patients treated with continuous positive airway pressure (CPAP) and to identify
      clinical and laboratory characteristics associated with mortality. DESIGN:
      Observational, retrospective study. SETTING: Emergency Medicine Department.
      PATIENTS AND PARTICIPANTS: A total of 454 consecutive ACPE patients treated with
      CPAP. MEASUREMENTS AND RESULTS: Demographics, past medical history, clinical
      characteristics, laboratory evaluation, in-hospital mortality data were
      collected. Potential predictors of in-hospital mortality that were considered of
      clinical relevance and immediately accessible on admission were investigated by
      multivariable logistic regression. ACPE-related mortality rate was 3.8% (17/452
      patients) and the in-hospital mortality rate was 11.4% (50/440 patients).
      Significant independent predictors of increased risk of in-hospital mortality
      were: advanced age (P = 0.012), normal-to-low blood pressure (P < 0.001), low
      PaO(2)/FiO(2) ratio (P = 0.020), hypocapnia (P = 0.009) and anemia (P = 0.05).
      CONCLUSIONS: Values recorded within few minutes from arrival to the hospital can
      predict mortality in ACPE patients treated with CPAP who has been tested, for the
      first time, in a real life study. This can allow physicians to quickly recognize
      more severe ACPE patients treated with CPAP and plan for aggressive monitoring
      and treatment and for deciding the better site of care.

PMID- 18807010
TI  - Osteopontin in sepsis: any role?

PMID- 18807011
TI  - Serum levels of osteopontin are increased in SIRS and sepsis.
AB  - OBJECTIVE: In sepsis, dysregulation of the immune response leads to rapid
      multiorgan failure and death. Accurate and timely diagnosis is lifesaving and
      should discriminate sepsis from the systemic inflammatory response syndrome
      (SIRS) caused by non-infectious agents. Osteopontin acts as an extracellular
      matrix component or a soluble cytokine in inflamed tissues. Its exact role in
      immune response and sepsis remains to be elucidated. Therefore, we investigated
      the role of osteopontin in SIRS and sepsis. DESIGN: Prospective, observational
      study. SETTING: Intensive care unit of a university hospital. PATIENTS AND
      PARTICIPANTS: Fifty-six patients with SIRS or sepsis and 56 healthy subjects were
      enrolled. INTERVENTIONS: We analyzed the serum levels of osteopontin and TH1-TH2
      cytokines and investigated the role of osteopontin on interleukin 6 secretion by
      monocytes. MEASUREMENTS AND MAIN RESULTS: Serum osteopontin levels were
      strikingly higher in patients than in controls and in sepsis than in SIRS, and
      decreased during the resolution of both the disorders. Receiver operating
      characteristic curves showed that osteopontin levels have discriminative power
      between SIRS and sepsis with an area under the curve of 0.796. Osteopontin levels
      directly correlated with those of interleukin 6 and in vitro, recombinant
      osteopontin increased interleukin 6 secretion by monocytes in both the absence
      and presence of high doses of lipopolysaccharide. CONCLUSION: These data suggest
      that osteopontin might be a mediator involved in the pathogenesis of SIRS and
      sepsis, possibly by supporting interleukin 6 secretion. DESCRIPTOR: 45.
      SIRS/Sepsis: clinical studies.

PMID- 18807012
TI  - Severe weakness complicating status asthmaticus despite minimal duration of
      neuromuscular paralysis.
AB  - OBJECTIVE: Mechanically ventilated patients with status asthmaticus who undergo
      prolonged paralysis are at risk for severe weakness due to myopathy. In the mid
      1990s, we changed our usual method of achieving tolerance of ventilatory support
      in asthmatic patients from continuous paralysis to deep sedation. This study
      examines the impact of this change in practice on the development of clinically
      significant weakness in status asthmaticus. DESIGN AND SETTING: Retrospective
      cohort study in university-affiliated county hospital. PATIENTS: Mechanically
      ventilated asthmatic patients seen before (n = 96) and after (n = 74) a clinical
      practice change in 1995 that markedly restricted use of paralytics. RESULTS: The
      duration of neuromuscular paralysis declined sharply after 1995 (23.7 +/- 42.2
      vs. 1.8 +/- 4.0 h, P < 0.001), but this was not associated with a significant
      difference in the incidence of weakness (21 vs. 14%, P = 0.23). Within the post
      1995 cohort, there was no significant difference in the duration of paralysis for
      weak and non-weak patients (3.5 +/- 6.2 vs. 1.5 +/- 3.5 h, P = 0.10). However,
      weak patients had a much longer duration of mechanical ventilation than did
      patients without weakness (11.9 +/- 3.6 vs. 1.9 +/- 1.8 days, P < 0.001).
      CONCLUSION: Mechanically ventilated patients with status asthmaticus who are
      immobilized for prolonged periods of time by deep sedation remain at risk for
      clinically significant weakness.

PMID- 18807013
TI  - Frequent and rare complications of resuscitation attempts.
AB  - INTRODUCTION: Resuscitation attempts require invasive iatrogenic manipulations on
      the patient. On the one hand, these measures are essential for survival, but on
      the other hand can damage the patient and thus contain a significant violation
      risk of both medical and forensic relevance for the patient and the physician. We
      differentiate between frequent and rare resuscitation-related injuries. Factors
      of influence are duration and intensity of the resuscitation attempts, sex and
      age of the patient as well as an anticoagulant medication. MATERIALS AND METHODS:
      Review of current literature and report on autopsy cases from our institute
      (approximately 1,000 autopsies per year). RESULTS: Frequent findings are lesions
      of tracheal structures and bony chest fractures. Rare injuries are lesions of
      pleura, pericardium, myocardium and other internal organs as well as vessels,
      intubation-related damages of neural and cartilaginous structures in the larynx
      and perforations of abdominal organs such as liver, stomach and spleen.
      CONCLUSION: We differentiate between frequent and rare complications. The risk of
      iatrogenic CPR-related trauma is even present with adequate execution of CPR
      measures and should not question the employment of proven medical techniques.

PMID- 18807014
TI  - Factors accelerating pyrimidine production in Deinococcus radiophilus.
AB  - In studying the pyrimidine synthesising pathway in Deinococcus radiophilus two
      instances of anomalous behaviour were observed. One was the strikingly different
      results obtained for two types of assay for carbamoyl phosphate synthetase. Both
      depend on the fixation of 14C from the substrate bicarbonate to give radioactive
      products. In the coupled assay the carbamoyl phosphate product of the enzyme is
      converted to carbamoyl aspartate in the presence of aspartate and aspartate
      transcarbamoylase. In the direct assay aspartate is omitted from the reaction
      mixture and the carbamoyl phosphate is converted to urea. It was found that the
      radioactive counts in the direct assay were about 5% of those measured in the
      coupled assay. The second anomaly was that omission of glutamine from both assay
      mixtures had no significant effect on the fixation of radioactive carbon. These
      results suggested that aspartate amino-N could be the source of nitrogen for
      glutamine synthesis by a substrate-channelled pathway which delivered glutamine
      to carbamoyl phosphate synthetase, and that externally added glutamine could not
      access its binding site on the enzyme.

PMID- 18807015
TI  - A glass microfluidic chip for continuous blood cell sorting by a magnetic
      gradient without labeling.
AB  - This paper presents a microfluidic chip for highly efficient separation of red
      blood cells (RBCs) from whole blood on the basis of their native magnetic
      properties. The glass chip was fabricated by photolithography and thermal
      bonding. It consisted of one inlet and three outlets, and a nickel wire of 69
      microm diameter was positioned in the center of a separation channel with 149
      microm top width and 73-microm depth by two parallel ridges (about 10 microm
      high). The two ridges were formed simultaneously during the wet etching of the
      channels. The nickel wire for generating the magnetic gradient inside the
      separation channel was introduced from the side of the chip through a guide
      channel. The external magnetic field was applied by a permanent magnet of 0.3 T
      placed by the side of the chip and parallel to the main separation channel. The
      RBCs were separated continuously from the 1:40 (v/v) diluted blood sample at a
      flow rate in the range 0.12-0.92 microL/min (9-74 mm/min) with the chip, and up
      to 93.7% of the RBCs were collected in the middle outlet under a flow rate of
      0.23 microL/min. The cell sedimentation was alleviated by adjusting the specific
      density of the supporting media with bovine serum albumin. Quantum dot labeling
      was introduced for visual fluorescence tracking of the separation process. The
      uneven distribution phenomenon of the blood cells around the nickel wire was
      reported and discussed.

PMID- 18807016
TI  - Separation and characterization of aluminium malate species by ion
      chromatography.
AB  - Aluminium malate complexes have a high relevance in biological systems. The
      anionic species present in an aqueous aluminium malate mixture can be
      investigated by ion chromatography coupled online with inductively coupled plasma
      atomic emission spectroscopy. As malic acid is a chiral ligand, the experiments
      were carried out using the racemic and the enantiopure forms. In both systems
      four anionic complexes are observable in the model solutions. One of two
      crystallized and well-characterized anions, [Al(4)Malate(6)](6-) and
      [Al(4)Malate(4)](2-), serves as a reference anion for the assignment of one of
      the species occurring in the model solutions. The main species in the enantiopure
      aluminium malate model with biological relevance over a wide pH range is the
      [Al(4)Malate(4)](2-) anion. The [Al(4)Malate(6)](6-) anion is not present in the
      racemic model solution. This anion suffers complete species disintegration after
      dissolution. The kinetics of the decay is first order and the activation energy
      of the decomposition is 74 kJ/mol. A retention model for ion chromatography was
      used for the determination of the effective charges of the species. The effective
      charge obtained by the retention model was calibrated in relation to nominal
      charges of the anions by using several well-defined and differently charged
      anions and anionic aluminium species.

PMID- 18807017
TI  - Protein microarrays for diagnostic assays.
AB  - Protein microarray technology has enormous potential for in vitro diagnostics
      (IVD). Miniaturized parallelized immunoassays are perfectly suited to generating
      a maximum of diagnostically relevant information from minute amounts of sample
      whilst only requiring small amounts of reagent. Protein microarrays have become
      well-established research tools in basic and applied research and the first
      products are already on the market. This article reviews the current state of
      protein microarrays and discusses developments and future demands relating to
      protein arrays in their role as multiplexed immunoassays in the field of
      diagnostics.

PMID- 18807018
TI  - Study of multiple binding constants of dexamethasone with human serum albumin by
      capillary electrophoresis-frontal analysis and multivariate regression.
AB  - Studies into the interactions between drugs and human serum albumin (HSA) are
      extremely important for drug discovery, since HSA behaves as a carrier for
      external drugs and internal biological molecules. In this paper, to evaluate the
      pharmacokinetic and pharmacodynamic properties of dexamethasone (DXM), the
      interaction between DXM and HSA was studied by capillary electrophoresis-frontal
      analysis (CE-FA). According to the Klotz equation, four binding sites between DXM
      and HSA were obtained, and the average binding constant was 1.05 x 10(3) M(-1).
      Furthermore, according to multiple equilibrium theory, based on the assumption
      that there are two types of binding site, the binding constant at one site was
      calculated to be 3.539 x 10(3) M(-1), and the average of the other three was
      1.234 x 10(3) M(-1). In addition, to obtain the detailed binding information at
      each binding site, new equations were deduced by multivariate regression. The
      four binding constants of DXM and HSA were calculated to be 5.558 x 10(1) M(-1),
      2.158 x 10(4) M(-1), 7.312 x 10(3) M(-1) and 2.043 x 10(3) M(-1), respectively,
      which is helpful for detailed studies into the interactions between drugs and
      proteins with multiple binding sites.

PMID- 18807019
TI  - Advances in the determination of degradation intermediates of personal care
      products in environmental matrixes: a review.
AB  - In this review, recent methods developed for the determination of degradation
      intermediates of personal care products in environmental matrixes focusing on the
      extraction and determination steps are discussed. The five classes of personal
      care products evaluated are stimulants, fragrances, sunscreens, antimicrobials,
      and insect repellents. Methods are critically reviewed in terms of the analytical
      steps involved in the analysis, sample pretreatment, separation, and detection as
      well as the different confirmation strategies employed. Preconcentration from
      aqueous matrixes was performed by solid-phase extraction, liquid-liquid
      extraction, or solid-phase microextraction, allowing the simultaneous extraction
      of parent compounds and their degradation intermediates. Following the extraction
      and cleanup steps, the identification and quantification of degradation
      intermediates of personal care products at environmental levels (i.e., parts per
      trillion to parts per billion range) is usually performed by using mass
      spectrometry techniques such as single quadrupole mass spectrometry and more
      recently by time-of-flight mass spectrometry or tandem mass spectrometry. The
      main scope of this review is to critically evaluate the current state of the art
      of the analytical techniques used and to identify the research needs in the
      determination of degradation intermediates of personal care products in
      environmental matrixes.

PMID- 18807020
TI  - Visual and cutaneous triggering of rapid step initiation.
AB  - The effects of a cutaneous imperative stimulus trigger cue (sural nerve
      stimulation) versus visual cuing of rapid step initiation were assessed in young,
      healthy subjects (n = 18). Two sets of experiments were conducted in which the
      vertical ground reaction force and EMG in tibialis anterior (TA) and gluteus
      medius (GM) were recorded in nine subjects and the vertical ground reaction force
      and center of pressure were recorded in a separate group of nine subjects.
      Subjects stood with one foot on a force platform with weight equally distributed
      and asked to take three steps as quickly as possible. A visual ready signal was
      followed at random times (0.5-2 s) by either a second visual go cue or
      stimulation of the sural nerve. Results revealed that sural cuing produced: (1)
      earlier onset times, greater vertical ground reaction forces and a greater rate
      of rise of force, (2) earlier onsets of TA and GM and greater mean EMG amplitudes
      in these muscles and (3) greater COP displacements in both the posterior and
      lateral direction. These results confirm previous reports on the functions of TA
      and GM in step initiation and further show that sural cuing enhances these EMG
      responses and the subsequent kinetic and kinematic changes associated with them.

PMID- 18807021
TI  - Misperceiving the speed-accuracy tradeoff: imagined movements and perceptual
      decisions.
AB  - Research has suggested that prospective motor decisions are consistent with
      actual motor action. In a study that we recently published (Young et al. in Exp
      Brain Res 185:681-688, 2008), however, participants demonstrated a preference for
      closer targets that was inconsistent with the predictions of Fitts's law. With a
      pair of experiments, the present paper investigates the underlying basis of this
      non-optimal behaviour. Participants showed a similar deviation from Fitts's law
      when imagining movements--believing that movement duration increased with
      distance within the same index of difficulty. Participants did not behave
      similarly, however, in a perceptual version of the decision task. These results
      suggest that imagined movements and motor decisions are linked, as well as
      demonstrating one situation in which both show a similar deviation from the
      patterns of actual movement duration.

PMID- 18807022
TI  - Position sense asymmetry.
AB  - Asymmetries in upper limb position sense have been explained in the context of a
      left limb advantage derived from differences in hemispheric specialization in the
      processing of kinesthetic information. However, it is not clearly understood how
      the comparison of perceptual information associated with passive limb
      displacement and the corresponding matching movement resulting from the execution
      of a motor command contributes to these differences. In the present study, upper
      limb position sense was investigated in 12 right-hand-dominant young adults
      performing wrist position matching tasks which varied in terms of
      interhemispheric transfer, memory retrieval and whether the reference position
      was provided by the same or opposite limb. Right and left hand absolute matching
      errors were similar when the reference and matching positions were produced by
      the same hand but were 36% greater when matching the reference position with the
      opposite hand. When examining the constant errors generated from matching
      movements made with the same hand that provided the reference, the right and left
      hand matching errors (approximately 3 degrees) were similar. However, when
      matching with the opposite limb, a large overshoot (P < 0.05) characterized the
      error when the right hand matched the left hand reference while a large
      undershoot (P < 0.05) characterized the error when the left hand matched the
      right hand reference. The overshoot and undershoot were of similar magnitude
      (approximately 4 degrees). Although asymmetries in the central processing of
      proprioceptive information such as interhemispheric transfer may exist, the
      present study suggests that asymmetries in position sense predominantly result
      from a difference in the "gain of the respective proprioceptive sensory-motor
      loops". This new hypothesis is strongly supported by a dual-linear model
      representing the right and left hand sensory-motor systems as well as
      morphological and physiological data.

PMID- 18807023
TI  - Eye-head coordination in moderately affected Huntington's Disease patients: do
      head movements facilitate gaze shifts?
AB  - In addition to many other symptoms, Huntington's Disease (HD) also causes an
      impairment of oculomotor functions. In particular, saccadic eye movements become
      progressively slower and more difficult to initiate; ultimately, patients are
      forced to recur to large head thrusts as means to initiate gaze shifts. We
      wondered whether, as a precursor of this condition, head movements would
      facilitate gaze shifts already in early stages of the disease. We studied
      horizontal head movements and eye-head coordination in 29 early stage HD patients
      (Ps) and 24 age matched controls (Cs). Subjects tracked random horizontal steps
      of visual or auditory targets while their heads were either stabilised (saccade
      amplitudes <or=40 degrees) or free to move (amplitudes <or=160 degrees). Subjects
      were to react either immediately (reactive mode), or wait until a go signal was
      sounded (delayed mode), or by antisaccades. Ps' head velocity was found to depend
      on the age of disease onset in a similar way as their saccadic eye velocity does,
      being clearly reduced in early affected Ps, but increasing to normal levels in
      lately affected Ps. Yet, saccade and head velocity were only loosely correlated
      although both exhibited a negative correlation with the severity of Ps' genetic
      condition (number of Ps' CAG repeats). Eye-head coordination turned out to be
      identical in Ps and Cs except for quantitative differences caused by the lower
      saccade and head velocities of Ps. Specifically, the timing between head and eyes
      and the head contribution to gaze shifts were similar in both groups. Moreover,
      preventing head movements did not affect the saccade latency or accuracy of Ps.
      Although Ps made more small involuntary head movements in this condition than Cs,
      these movements were not instrumental in generating saccades since they occurred
      only late after saccade onset. Thus, the head manoeuvres of severely affected
      patients must be considered a late adaptive behaviour. Finally, the ability of
      both Ps and Cs to suppress immediate reactions in the delayed and antisaccade
      conditions diminished as target distance decreased, with failure rates in Ps
      being much larger than in Cs. Unlike eye and head velocity, these failure rates
      were not correlated with age and, by the same token, neither with the variations
      in head and eye velocity nor with the number of CAG repeats. Hence, the pattern
      of brain areas prominently affected by HD is likely to vary significantly among
      individuals.

PMID- 18807024
TI  - Stents for intracranial wide-necked aneurysms: more than mechanical protection.
AB  - Treatment of wide-necked aneurysms by endovascular coil embolization usually
      requires mechanical aids in order to protect the parent artery from occlusion due
      to extension of coils or thrombosis. Endovascular stents are one tool that can be
      deployed to solve this essentially mechanical problem. The effect of a stent
      placed in the situation may also act as a hemodynamically active flow diverter.
      Endovascular stents used in other circumstances are prone to the unwanted side
      effect of neoinitmal proliferation, but this phenomenon should be seen as a
      potential asset for "aneurysmal stents" because it may lead to a reaction that
      contributes to vessel wall healing.

PMID- 18807025
TI  - Abciximab for thrombolysis during intracranial aneurysm coiling.
AB  - INTRODUCTION: Thrombotic events are a common and severe complication of
      endovascular aneurysm treatment with significant impact on patients' outcome.
      This study evaluates risk factors for thrombus formation and assesses the
      efficacy and safety of abciximab for clot dissolution. MATERIALS AND METHODS: All
      patients treated with abciximab during (41 patients) or shortly after (22
      patients) intracranial aneurysm coil embolisation were retrieved from the
      institutional database (2000 to 2007, 1,250 patients). Sixty-three patients (mean
      age, 55.3 years, +/- 12.8) had received either intra-arterial or intravenous
      abciximab. Risk factors for clot formation were assessed and the angiographic and
      clinical outcome evaluated. RESULTS: No aneurysm rupture occurred during or after
      abciximab application. The intra-procedural rate of total recanalisation was
      68.3%. Thromboembolic complications were frequently found in aneurysms of the
      Acom complex and of the basilar artery, whilst internal carotid artery aneurysms
      were underrepresented. Two patients died of treatment-related intracranial
      haemorrhages into preexisting cerebral infarcts. Two patients developed a
      symptomatic groin haematoma. CONCLUSIONS: Abciximab is efficacious and safe for
      thrombolysis during and after endovascular intracranial aneurysm treatment in the
      absence of preexisting ischaemic stroke.

PMID- 18807026
TI  - Automated structure determination from NMR spectra.
AB  - Automated methods for protein structure determination by NMR have increasingly
      gained acceptance and are now widely used for the automated assignment of
      distance restraints and the calculation of three-dimensional structures. This
      review gives an overview of the techniques for automated protein structure
      analysis by NMR, including both NOE-based approaches and methods relying on other
      experimental data such as residual dipolar couplings and chemical shifts, and
      presents the FLYA algorithm for the fully automated NMR structure determination
      of proteins that is suitable to substitute all manual spectra analysis and thus
      overcomes a major efficiency limitation of the NMR method for protein structure
      determination.

PMID- 18807027
TI  - Identifying Escherichia coli genes involved in intrinsic multidrug resistance.
AB  - Multidrug resistance is a major cause of clinical failure in treating bacterial
      infections. Increasing evidence suggests that bacteria can resist multiple
      antibiotics through intrinsic mechanisms that rely on gene products such as
      efflux pumps that expel antibiotics and special membrane proteins that block the
      penetration of drug molecules. In this study, Escherichia coli was used as a
      model system to explore the genetic basis of intrinsic multidrug resistance. A
      random mutant library was constructed in E. coli EC100 using transposon
      mutagenesis. The library was screened by growth measurement to identify the
      mutants with enhanced or reduced resistance to chloramphenicol (Cm). Out of the
      4,000 mutants screened, six mutants were found to be more sensitive to Cm and
      seven were more resistant compared to the wild-type EC100. Mutations in 12 out of
      the 13 mutants were identified by inverse polymerase chain reaction. Mutants of
      the genes rob, garP, bipA, insK, and yhhX were more sensitive to Cm compared to
      the wild-type EC100, while the mutation of rhaB, yejM, dsdX, nagA, yccE, atpF, or
      htrB led to higher resistance. Overexpression of rob was found to increase the
      resistance of E. coli biofilms to tobramycin (Tob) by 2.7-fold, while
      overexpression of nagA, rhaB, and yccE significantly enhanced the susceptibility
      of biofilms by 2.2-, 2.5-, and 2.1-fold respectively.

PMID- 18807028
TI  - Modic changes in vertebral endplates: a comparison of MR imaging and multislice
      CT.
AB  - OBJECTIVE: This paper aims to evaluate the presence of endplate sclerosis in
      different types of Modic changes and to assess the capability of MRI in detecting
      endplate sclerosis within these changes. MATERIALS AND METHODS: The lumbar spines
      (L3-S1) of 70 patients were retrospectively reviewed to determine Modic changes
      and disc degeneration from MRI and endplate sclerosis from CT. T1- and T2
      weighted signal intensity and Hounsfield unit (HU) measurements of type I and II
      Modic changes were recorded and the association of both Modic types I and II with
      endplate sclerosis was analyzed with a Mann-Whitney test. RESULTS: Altogether 82
      Modic changes in 36 subjects were recorded: 13% were type I, 12% mixed type I/II,
      65% type II, 9% mixed type II/III, and 1% type III. Thirty-eight percent of the
      endplates with Modic changes had sclerosis in CT. Of specific Modic types, mixed
      I/II and II/III associated significantly with endplate sclerosis. Endplate
      sclerosis was not detected in MRI in a quantitative analysis. CONCLUSION:
      Endplate sclerosis exists in all types of Modic changes, especially in mixed
      Modic types, and not only in type III changes, as previously assumed. Endplate
      sclerosis was not detected in MRI, which may depend on the amount of
      mineralization of the bone marrow.

PMID- 18807029
TI  - Haemophilia imaging: a review.
AB  - Haemophilia disorders are characterised by a blood coagulation anomaly leading to
      prolonged and excessive bleeding. Imaging provides an essential role in the
      investigation of both the musculoskeletal and the non-musculoskeletal
      complications of haemophilia. Our institution is home to a large tertiary
      referral centre for haemophilia treatment. Using our broad experience, we present
      a multi-modality pictorial review of the musculoskeletal manifestations of
      haemophilia, including haemophilic arthropathy, intra-muscular haemorrhage and
      haemophilic pseudotumour. The main imaging features of haemophilic arthropathy
      are described, including synovial hypertrophy, haemosiderin deposition, sub
      chondral cyst formation and loss of joint space.

PMID- 18807030
TI  - Chromomycosis presenting as soft-tissue mass: report of a case with MRI features.
AB  - Chromomycosis is primarily a skin disease that superficially presents as slowly
      growing, verrucous lesions, often warty or cauliflower-like in appearance. It may
      occasionally create a flat, plaque-like lesion in the skin but deep-seated
      tumorous presentation has not previously been reported. As the lesion is limited
      to the cutaneous and superficial subcutaneous tissues, hitherto reported cases
      have been described from the view point of dermatology and, so, without MRI
      study. We report a patient with pathologically proven chromomycosis that produced
      a subcutaneous mass in the dorsum of the hand with an emphasis on MRI features.

PMID- 18807031
TI  - Persistent swelling at the ankle joint: presentation, diagnosis and discussion.

PMID- 18807033
TI  - Correlation of immunohistopathological expression of somatostatin receptor 2 with
      standardised uptake values in 68Ga-DOTATOC PET/CT.
AB  - PURPOSE: In clinical routine somatostatin analogue positron emission
      tomography/computed tomography (PET/CT) such as (68)Ga-DOTA-Tyr-octreotide
      (DOTATOC)-PET/CT could substitute conventional (111)In-Octreotide scintigraphy.
      Immunohistochemistry (IHC) for somatostatin receptor 2 (SSTR2) might be a tool to
      predict positivity of (68)Ga-DOTATOC in patients where initial staging was not
      performed, e.g., in incidental findings. We therefore compared a score of SSTR2
      IHC with the in vivo standard uptake value (SUV) of preoperative or prebiopsy
      (68)Ga-DOTATOC PET/CT. MATERIALS AND METHODS: In 18 patients, (68)Ga-DOTATOC
      PET/CT scans were quantified with SUV calculations and correlated to a cell
      membrane-based SSTR2-IHC score (ranging from 0 to 3). RESULTS: Negative IHC
      scores were consistent with SUV values below 10. Furthermore, all score 2 and 3
      specimens corresponded with high SUV values (above 15). CONCLUSION: SSTR2-IHC
      scores correlated well with SUV values and we propose to use SSTR2
      immunohistochemistry in patients missing a preoperative PET scan to indicate
      (68)Ga-DOTATOC-PET/CT as method for restaging and follow-up in individual
      patients.

PMID- 18807034
TI  - Myocardial perfusion scintigraphy in Europe 2005: a survey of the European
      Council on Nuclear Cardiology.
AB  - PURPOSE: We have conducted a survey of myocardial perfusion scintigraphy (MPS) in
      2005 in Europe with the intention of initiating a regular series of surveys to
      track usage of the technique. METHODS: Information was obtained from 234 centres
      in 18 counties. The returning centres served 27% of the population of their
      countries, and estimates of the numbers of MPS per million of population (pmp)
      were made assuming that the population not reported either performed no studies
      (lower estimate) or the same number pmp as the reporting centres (upper
      estimate). RESULTS: Estimates of MPS for the countries surveyed ranged from a
      lower limit of 373 pmp to an upper limit of 1,388 pmp. There were marked
      variations between countries with higher numbers (lower limit of estimate above
      the mid range of all countries combined) in Austria, Greece, Hungary, The
      Netherlands, Sweden and Slovenia, and lower numbers (upper limit of estimate
      below the mid range of all countries) in Finland, Germany and Poland. The ratio
      of MPS to coronary angiography to revascularisation procedures was 0.6 to 1.5 to
      1. The median number of studies per centre was 496, with 32% of centres
      performing fewer than 250 studies in the year. The median waiting time for
      routine studies was 21 days and for urgent studies 3.4 days. Fifty-three percent
      of studies used pharmacological stress, with roughly equal numbers of adenosine
      and dipyridamole. Eighty-two percent of studies used (99m)Tc-based tracers.
      Tomographic acquisition was almost universal with 65% of studies being ECG-gated
      and 20% attenuation-corrected. Eighteen percent of studies were reported from
      hard copy alone, and 60% of studies were reported without viewing the rotating
      planar data. CONCLUSION: We conclude that relatively low numbers of MPS studies
      are being performed in the surveyed centres, particularly when compared with
      coronary angiography and revascularisation. The use of (99m)Tc-based tracers is
      high, but ECG-gated studies are less common. Some reporting practices are not
      ideal. These data will serve as a valuable baseline for future surveys, which are
      likely to be more complete.

PMID- 18807035
TI  - Immunosensitization with a Bcl-2 small molecule inhibitor.
AB  - Several tumor immunotherapy approaches result in a low percentage of durable
      responses in selected cancers. We hypothesized that the insensitivity of cancer
      cells to immunotherapy may be related to an anti-apoptotic cancer cell milieu,
      which could be pharmacologically reverted through the inhibition of antiapoptotic
      Bcl-2 family proteins in cancer cells. ABT-737, a small molecule inhibitor of the
      antiapoptotic proteins Bcl-2, Bcl-w and Bcl-x(L), was tested for the ability to
      increase antitumor immune responses in two tumor immunotherapy animal models. The
      addition of systemic therapy with ABT-737 to the immunization of BALB/c mice with
      tumor antigen peptide-pulsed dendritic cells (DC) resulted in a significant delay
      in CT26 murine colon carcinoma tumor growth and improvement in survival. However,
      the addition of ABT-737 to either a vaccine strategy involving priming with TRP-2
      melanoma antigen peptide-pulsed DC and boosting with recombinant Listeria
      monocytogenes expressing the same melanoma antigen, or the adoptive transfer of
      TCR transgenic cells, did not result in superior antitumor activity against B16
      murine melanoma. In vitro studies failed to demonstrate increased cytotoxic lytic
      activity when testing the combination of ABT-737 with lymphokine activated killer
      (LAK) cells, or the death receptor agonists Fas, TRAIL-ligand or TNF-alpha
      against the CT26 and B16 cell lines. In conclusion, the Bcl-2 inhibitor ABT-737
      sensitized cancer cells to the antitumor effect of antigen-specific immunotherapy
      in a vaccine model for the CT26 colon carcinoma in vivo but not in two
      immunotherapy strategies against B16 melanoma.

PMID- 18807036
TI  - Is management with lamivudine always the appropriate choice for HBV patients with
      onco-hematologic diseases?

PMID- 18807037
TI  - Mathematical modelling of the influence of heat shock proteins on cancer invasion
      of tissue.
AB  - Tumour cell invasion is crucial for cancer metastasis, which is the main cause of
      cancer mortality. An important group of proteins involved in cancer invasion are
      the Heat Shock Proteins (HSPs). According to experimental data, inhibition of one
      of these proteins, Hsp90, slows down cancer cells while they are invading tissue,
      but does not affect the synthesis of matrix metalloproteinases (MMP2 and MMP9),
      which are very important for cancer metastasis, acting as extracellular matrix
      (ECM) degrading enzymes. To test different biological hypotheses regarding how
      precisely Hsp90 influences tumour invasion, in this paper we use a model of solid
      tumour growth which accounts for the interactions between Hsp90 dynamics and the
      migration of cancer cells and, alternatively, between Hsp90 dynamics and the
      synthesis of matrix degrading enzymes (MDEs). The model consists of a system of
      reaction-diffusion-taxis partial differential equations describing interactions
      between cancer cells, MDE, and the host tissue (ECM). Using numerical simulations
      we investigate the effects of the administration of Hsp90 inhibitors on the
      dynamics of tumour invasion. Alternative mechanisms of reduction of cancer
      invasiveness result in different simulated patterns of the invading tumour cells.
      Therefore, predictions of the model suggest experiments which might be performed
      to develop a deeper understanding of the tumour invasion process.

PMID- 18807038
TI  - [Early loss of heterozygosity on chromosome arm 16q in flat epithelial atypia of
      the breast. Detection by microsatellite analyses].
AB  - With the improvement of breast carcinoma screening, pre-malignant cell lesions
      such as flat epithelial atypia (FEA) are detected more frequently. Several
      studies have demonstrated that FEA show features of a ductal neoplasia, but is it
      really a precursor lesion? We have started a comparative genetic analysis of a
      panel of nine microsatellite markers on six different chromosomal regions to
      investigate whether FEAs show the same characteristic genetic alterations as
      ductal carcinomas in situ (DCISs) and invasive carcinoma of the breast. FEAs,
      DCISs and invasive carcinomas of the same patients were microdissected using PALM
      micro laser technology. DNA was isolated using the QIAamp DNA Micro Kit (QIAGEN).
      We have investigated a set of the polymorphic microsatellite markers D7S522,
      D8S522, NEFL, D10S541 (PTEN), D13S153 (RB1), D16S400, D16S402, D16S422 and
      D17S855 (BRCA1) using multiplex PCR for the detection of allelic imbalances. Most
      of the investigated FEAs showed a lower frequency of loss of heterozygosity than
      associated DCISs or invasive carcinomas. However, we were able to detect the same
      alterations in FEAs as in DCISs or invasive carcinomas in a number of cases.
      Notably, the microsatellite marker on 16q showed more prevalent allelic
      imbalances in FEAs than the other investigated markers. One of the hallmarks in
      the pathogenesis of a large subgroup of invasive breast carcinomas is the early
      loss of chromosome arm 16q. In this study, we were able to detect frequent
      genetic alterations on chromosome 16q in FEAs, associated DCISs and invasive
      carcinomas. This suggests that FEA is a precursor lesion in the low-grade
      pathway.

PMID- 18807039
TI  - [Promoter methylation of ID4. A marker for recurrence-free survival in human
      breast cancer].
AB  - The aim of this study was to unravel the role of the transcription factor
      inhibitor of DNA binding 4 (ID4) in human breast carcinogenesis in more detail,
      especially the impact of ID4 promoter methylation on disease progression.
      Demethylating treatment of breast cancer cell lines was associated with ID4
      reexpression. ID4 promoter methylation was frequently observed in primary breast
      cancer samples (68.9%, 117/170). We found a very tight correlation (p<0.001)
      between ID4 promoter methylation and loss of ID4 mRNA expression in these
      specimens. For breast tissue as the first tumour entity analyzed in detail, we
      could show a direct correlation between ID4 promoter methylation and loss of ID4
      expression on both the mRNA and protein level. Interestingly, ID4 promoter
      methylation was a factor for unfavourable recurrence-free survival (p=0.036) and
      increased the patient's risk for lymph node metastases (p=0.030). Our data
      suggest that ID4 is a potential tumour suppressor gene in human breast tissues
      that undergoes epigenetic silencing during carcinogenesis, leading to an
      increased risk for tumour relapse. Thus, ID4 methylation status could serve as a
      prognostic biomarker in human breast cancer.

PMID- 18807040
TI  - [Basal and myoepithelial phenotype of metastatic mammary carcinomas. A prognostic
      factor in the palliative situation?].
AB  - AIMS: The aim of the present study was to evaluate the prognostic impact of basal
      and myoepithelial phenotype in breast carcinomas (BBC and MBC) in the palliative
      situation. METHODS: Paraffin-embedded material from 244 primary breast carcinomas
      of patients with subsequent metastatic disease was stained immunohistochemically
      for CK 5/6, CK14, smooth-muscle actin, p63, estrogen receptor and progesterone
      receptor. BBC was defined as positive for CK5/6 and/or CK14 and MBC as positive
      for SMA and/or p63. Clinical and pathological data were available for all
      patients and follow-up data for 96.3% (range 5 days-151 months). RESULTS: Until
      the end of the follow-up period 90.2% of patients died and 6.1% are still alive.
      Of the tumours 28.7% could be classified as BBC and 8.2% as MBC. Kaplan Meier
      analysis revealed a trend for reduced survival after first diagnosis of
      metastasis (OASM) for BBC and MBC. Differences in survival were significant for
      BBC (log-rank =5.0; p=0.025), but not for MBC. CK5/6+ and CK14+ double positive
      tumours (n=18; 7.4%) were identified as a subgroup of BBC associated with reduced
      OASM (log-rank=8,6; p=0.003). This subgroup, but not BBC or MBC was an
      independent negative prognostic factor in a multivariate analysis including age,
      typing, tumour size, grading, axillary nodes, HR, Her2/neu, site of first
      metastasis and disease-free interval. CONCLUSION: The association of BBC and MBC
      with reduced OASM in metastatic breast carcinomas is not independent from
      established prognostic factors. CK5/6+ CK14+ double positive tumours may be a
      subgroup of BBC with particularly unfavourable outcome.

PMID- 18807041
TI  - [Mammography screening. Concept, quality assurance and interdisciplinary
      cooperation].
AB  - In 2005/2006 the German National Mammography Screening Program was initiated and
      has now become established. The objective is to reduce breast cancer mortality
      and the early diagnosis and therapy of small cancers. The program follows the
      European guidelines and is controlled by over 30 parameters of quality. All
      trained members of the team document each step of the screening chain
      electronically. Histological assessment (HA) is recommended in up to 2% of
      examinations, 90% of HAs are performed by core needle biopsy (CNB) or by
      stereotactic vacuum-assisted biopsy (VABB). Open diagnostic biopsies are
      performed in <10% of all HAs and therapy is successful in some of the B3 lesions.
      Mammograms are interpreted by two independent readers. Recommendations of the
      regular interdisciplinary conferences, preoperative and postoperative, follow the
      European guidelines. About 45% of all breast cancers detected by screening are in
      situ or less than 10 mm in size. The 17% alterations diagnosed by needle biopsy
      are B3 or B4 lesions and impose high demands on the pathologists and the
      interdisciplinary team. Due to the many early and discrete lesions
      counterchecking of representative biopsies is crucial. Problems may be caused by
      sampling error or partial volume effects. Interdisciplinary conferences and
      knowledge of the limitations of each discipline and method are needed to optimize
      diagnostic and therapeutic decisions.

PMID- 18807042
TI  - [Minutes of the meeting of the German Society of Pathology's working group on
      informatics. Berlin, 15 May 2008].

PMID- 18807043
TI  - Nuclear export of Ho endonuclease of yeast via Msn5.
AB  - Exportin-5, an evolutionarily conserved nuclear export factor of the beta
      karyopherin family, exports phosphorylated proteins and small noncoding RNAs.
      Msn5, the yeast ortholog, exports primarily phosphorylated cargoes including Ho
      endonuclease and a number of transcription factors and regulatory proteins. The
      Msn5-mediated nuclear export of Ho is dependent on phosphorylation of Thr225 by
      kinases of the DNA damage response pathway. Although Msn5 has been the object of
      many studies, no NES sequence capable of binding the exportin and/or of leading
      to Msn5-dependent export of a heterologous protein has been identified. Here we
      report identification of a 13-residue Ho sequence that interacts with Msn5 in
      vitro and directs Msn5-dependent nuclear export of GFP in vivo. A single point
      mutation in this 13-mer Ho NES abrogates both interaction with Msn5 and nuclear
      export of Ho and of GFP. However, this mutation, or of T225A, both of which
      abrogate nuclear export of Ho, does not interfere with its interaction with Msn5
      implying that the exportin makes multiple contacts with its cargo. This can
      explain the lack of a conserved NES in Msn5 cargoes. Our results identify
      essential criteria for Msn5-mediated nuclear export of Ho: phosphorylation on
      HoT225, and interaction with the 13-mer Ho NES sequence.

PMID- 18807044
TI  - Henoch-Schonlein Purpura with thrombocythaemia: an abnormality in Smad4
      expression?
AB  - We discuss a patient with Henoch-Schonlein Purpura (HSP) and a thrombocythaemia
      which was diagnosed as a coincidental Essential Thrombocythaemia. We suggest that
      deficiencies in Smad4 expression may allow for escape thrombocythaemia under the
      influence of the high levels of TGF-beta found in HSP. With normal Smad4
      expression TGF-beta provides inhibition of thrombocyte proliferation. While this
      needs further elucidation, it could lead to a new approach to classification and
      management of HSP.

PMID- 18807045
TI  - Anasarca as the presenting manifestation of parvovirus B19 associated juvenile
      dermatomyositis.
AB  - Anasarca as the presenting manifestation of juvenile dermatomyositis (JDMS) is
      extremely rare. We report a case of a 4-year-old boy who was initially managed
      for nephrotic syndrome in view of anasarca and mild hypoalbuminemia. Later, at
      presentation to our institute, a diagnosis of severe edematous JDMS was made in
      view of associated profound muscle weakness and characteristic skin changes. The
      child responded to aggressive immunosuppressive therapy. On further evaluation,
      he had evidence of acute parvovirus B19 infection. Our case illustrates anasarca
      as an uncommon severe manifestation of JDMS and the possible role of parvovirus
      B19 in the onset of this autoimmune disorder.

PMID- 18807046
TI  - Chromosome elimination and in vivo haploid production induced by Stock 6-derived
      inducer line in maize (Zea mays L.).
AB  - In vivo haploid production induced by inducer lines derived from Stock 6 is
      widely used in breeding program of maize (Zea mays L.), but the mechanisms behind
      have not yet been fully understood. In this study, average frequency of haploid
      induction in four inbred lines by Stock 6-derived inducer line HZI1 was above
      10%. About 0.2% kernels from the cross Hua24 x HZI1 had mosaic endosperm showing
      yellow shrunken parts from Hua24 to normal parts with purple aleurone from HZI1.
      Individual lagged chromosomes and micronuclei were observed in mitotic cells of
      ovules pollinated by HZI1. Above 56.4% of the radicles from the kernels with
      purple aleurone and colorless embryos were mixoploid (2n = 9-21), and more than
      45.22% cells were haploid cells (2n = 10) in three crosses. More than 62.5% of
      the radicles from the kernels with purple aleurone and purple embryos were
      mixoploid (2n = 9-21) having 54.27% cells with 2n = 20. SSR analysis showed that
      all haploids from the cross Hua24 x HZI1 shared the same genomic compositions as
      Hua24 except for plants Nos. 862 and 857 with some polymorphic DNA bands. The
      results revealed that chromosome elimination after fertilization caused the
      haploid production in maize.

PMID- 18807047
TI  - Management of low-risk prostate cancer.

PMID- 18807048
TI  - Does 3-Dimensional (3-D) visualization improve the quality of assistance during
      robotic radical prostatectomy?
AB  - OBJECTIVE: 3-Dimensional (3-D) visualization by the surgeon is considered to be
      one of the major advantages of robotic prostatectomy. We undertook this study to
      see if passing on this technology to the surgical assistants would improve the
      efficiency of their assistance. MATERIALS AND METHODS: The study was conducted in
      consecutive patients undergoing robotic radical prostatectomy by the same team,
      in one month at our center. A 3-D head mounted device (HMD) was used by the left
      and/or right assistant. Video recording from these patients were studied by a
      blinded observer with prior training in laparoscopic surgery for the efficiency
      of laparoscopic moves by the two assistants. These moves were scored on a point
      scoring system from 0 to 100 with 100 signifying the best possible performance.
      RESULTS: After exclusions, 26 videos were available for review. Each patient had
      a right and left-sided assistant. The right-sided assistant had prior experience
      in Laparoscopic Urology, and the left-sided assistant had a relatively limited
      laparoscopic experience. The mean scores for the left assistant improved from
      76.3 to 84.6 with the use of 3-D visualization (p < 0.002), while the improvement
      for the right assistant was from 84.1 to 86.9 (NS). CONCLUSIONS: The use of 3-D
      visualization possibly improves the efficiency of assistance during robotic
      radical prostatectomies, for the assistant with limited experience in
      laparoscopic surgery. Because of the high-quality 3-D vision provided, these HMDs
      have the potential to be used as teaching aids in the robotic lab.

PMID- 18807049
TI  - Analysis of complications from 600 retroperitoneoscopic procedures of the upper
      urinary tract during the last 10 years.
AB  - INTRODUCTION: The aim of this study is to review 10 years experience of
      retroperitoneoscopy procedures. METHODS: A total of 600 patients treated between
      1995 and 2007 by retroperitoneoscopy (nephrectomy, partial and total nephrectomy,
      adrenalectomy, pyeloplasty, renal cyst, calyceal diverticulectomy) were reviewed
      for per, peri and postoperative complications including patients in the learning
      curve. RESULTS: The mean blood loss was 159 mL. Conversion to open surgery was
      required in 28 patients (4.6%) primarily due to technical problems during
      dissection (elective). There were 32 (5.3%) surgical complications, including
      bleeding or hematomas in 12 cases and 2 of them required reintervention, urinomas
      in 8 which were treated by installation of a ureteral drainage (JJ stent). Wound
      or deep abscesses happened in four, urinary fistula in one and pancreatic fistula
      in another. Evisceration (hernias) was seen in three patients. Intestinal injury
      occurred in two. The complication rate depended on the difficulty of the
      procedure and learning curve of the surgeon. A total of 28 patients (4.6%)
      presented medical postoperative complications (hyperthermias, deep venous
      thrombosis, pyelonephritis, pulmonary superinfections, pulmonary atelectasia and
      transient vascular ischemic accident). Mean postoperative hospital stay was 6.2
      days (ranged from 2 to 20). CONCLUSION: Retroperitoneoscopy can be the technique
      of choice for accessing and carrying out all the surgery of the upper urinary
      tract respecting the principles of oncological surgery. After experience with 600
      cases during the last 10 years the technique has become safe, simplified,
      reproducible and effective although not easy. Most complications are minor and
      easily managed.

PMID- 18807050
TI  - The oxygen-binding modulation of hemocyanin from the Southern spiny lobster
      Palinurus gilchristi.
AB  - Arthropod hemocyanins transport and store oxygen and are composed of six
      subunits, or multiples thereof depending on the species. Palinurus gilchristi
      hemocyanin is found only as 1 x 6-mers, as normally occurs in spiny lobsters. An
      alkaline pH and removal of calcium ions induce a wholly reversible dissociation
      into monomers. The oxygen-binding properties of 1 x 6-meric hemocyanin from P.
      gilchristi were investigated with respect to pH and modulating effect exerted by
      calcium, lactate and urate. The oxygen affinity was highly affected by pH in the
      presence of calcium ions, while in its absence the Bohr coefficient became 60%
      lower. The protein is insensitive to lactate, but affected by urate which
      markedly increased hemocyanin-oxygen affinity, acting as the physiological major
      positive effector. Calcium ions decrease oxygen affinity at low concentration
      range (0-1 mM), while as concentration becomes higher than 100 mM, the oxygen
      affinity increases, indicating the presence of two independent types of calcium
      binding sites with high and low affinity, respectively. The previous hypothesis,
      that the presence of high-affinity binding sites in addition to low affinity ones
      could be a characteristic feature of Palinuran hemocyanins, has been tested by
      analyzing, with respect to calcium-hemocyanin interaction, three other species
      belonging to Palinura.

PMID- 18807051
TI  - Hepatoduodenal ligament teratoma with hepatic artery running inside.
AB  - Teratoma in infants and children is not particularly rare. However, the teratoma
      in the hepatoduodenal ligament is extremely rare and the surgical treatment is
      challenging because of its anatomical complexity. We could find only six cases in
      the literature. In this report, we present the seventh case with special
      reference to the operative technique to save the hepatic artery for resection of
      the tumor using intraoperative ultrasonography.

PMID- 18807052
TI  - Periprosthetic humeral fractures after shoulder arthroplasty: operative
      management and functional outcome.
AB  - BACKGROUND: Currently, little information is available on functional outcome of
      periprosthetic humeral fractures after shoulder arthroplasty. This investigation
      aimed to evaluate functional and radiological outcome and patients' satisfaction
      following this type of injury treated by open reduction and internal fixation.
      METHODS: Retrospective chart analysis of patients treated at two level-I trauma
      centers. Patients were examined clinically and radiologically. Additionally,
      functional outcome was assessed using the established DASH-questionnaire and
      standardized examination for calculation of the Constant score. RESULTS: Five out
      of six patients showed complete fracture consolidation with satisfying functional
      results (mean follow up time 62 weeks). One patient showed major complications
      with poor outcome. DASH and Constant scores were comparable to those described
      after primary shoulder arthroplasty. CONCLUSIONS: Periprosthetic humeral
      fractures after shoulder arthroplasty can be treated by angular stable plating
      with low complication rates and acceptable results.

PMID- 18807053
TI  - Benefit of a 17-year long-term bisphosphonate therapy in a patient with Gorham
      Stout syndrome.
AB  - This case report of a 61-year-old woman suffering from Gorham-Stout syndrome
      shows osteolyses of the left pelvis, proximal femur and lumbar spine. The
      therapeutic regime has included two courses of percutaneous radiotherapy and also
      continuous application of bisphosphonates over 17 years. Despite this
      antiresorptive therapy, elevated urinary excretion of desoxypyridinoline has
      indicated the persistence of increased bone destruction. The radiological
      progression following bisphosphonate treatment was only moderate. However,
      physical disability is reduced, but without soaring handicaps suggesting that
      long-term bisphophonate therapy is a therapeutical option for this rare syndrome.

PMID- 18807054
TI  - Results of the tension-free vaginal tape procedure for treatment of female stress
      urinary incontinence: a 5-year follow-up study.
AB  - OBJECTIVE: We evaluated the long-term cure rates, surgical complications rates
      after treatment of urodynamically confirmed primary genuine stress incontinence
      with tension-free vaginal tape (TVT). METHODS: We performed a retrospective
      review of all patients undergoing the TVT procedure over a 5-year period to
      report intraoperative complication, postoperative complications and subjective
      cure rates. RESULTS: TVT was performed on 600 patients under general anesthesia.
      Among these patients, 563 were followed up for least 5 years; the remaining 47
      patients could not be followed up. The mean follow-up interval was 63.1+/-3.1
      (range 60-70) months. The mean age of the women was 51.7+/-11.6 years and mean
      body mass index 31.7+/-3.0 kg/m(2). Sixty-two percent (347) of women underwent
      the TVT procedure in conjunction with other vaginal surgery, and 38% (216)
      underwent TVT alone. The subjective analysis of the effect of surgery on the
      symptom of GSI was that, overall, 86.7% were completely cured, 6.0% were
      significantly improved and 7.3% found no change in the severity of her
      incontinence. No major nerve or vessel injury occurred, but 17 patients (3.0%)
      incurred bladder injury during the surgery. De novo voiding urgency occurred in
      36 patients (6.4%). Thirty patients (5.3%) developed voiding problem, of which 19
      patients had short-term voiding problem. CONCLUSION: The TVT procedure is a
      relatively safe and effective, minimally invasive surgical technique for the
      treatment of female urinary stress incontinence.

PMID- 18807055
TI  - Complex Nabothian cysts: a diagnostic dilemma.
AB  - BACKGROUND: Multiple and large cysts, located in the cervical stroma, can cause
      significant enlargement of the cervix. CASE: A woman with two large intracervical
      cysts, one complex, underwent evaluation with ultrasound and magnetic resonance
      imaging (MRI). Hysterectomy revealed Nabothian cysts. CONCLUSION: In rare cases
      in which the intracervical cysts assume very large dimensions, ultrasound and MRI
      can aid diagnosis, but may not always prevent the need for excision or
      hysterectomy.

PMID- 18807056
TI  - Coexistence of struma ovarii with marked ascites and elevated CA-125 levels: case
      report and literature review.
AB  - INTRODUCTION: Struma ovarii is a rare form of ovarian neoplasm and consists
      mainly of thyroid tissue. Ascites has been reported in approximately one-third of
      all the cases. However, the combination of struma ovarii and elevated CA-125 has
      rarely been reported. MATERIALS AND METHODS: We described a case of benign struma
      ovarii, presenting with the clinical features of ovarian cancer: large complex
      pelvic mass, gross ascites and markedly elevated serum CA-125 levels. Surgical
      excision of the ovarian mass was followed by rapid resolution of the ascites and
      reduction of the serum CA-125 level. CONCLUSION: Struma ovarii can mimic ovarian
      malignancy clinically, when presented with ascites and an elevated CA-125 level.

PMID- 18807057
TI  - Long-term outcomes after tympanoplasty with and without mastoidectomy for
      perforated chronic otitis media.
AB  - The objectives of the retrospective study, performed at a tertiary referral
      center, were to examine the prognostic factors predicting long-term outcomes of
      tympanoplasty for perforated chronic otitis media (COM) and to determine whether
      mastoidectomy can be avoided during tympanoplasty for perforated COM. Between
      1987 and 2002, 213 patients with perforated COM underwent tympanoplasty by the
      same surgeon and were followed for more than 5 years. Postoperative hearing
      outcomes were considered successful, if the postoperative air-bone gap was within
      20 dB. Closure of perforation by a single surgery was considered a successful
      graft. Long-term outcomes were analyzed using logistic regression analysis.
      Normal ossicular chain was the only factor that showed a significantly favorable
      relation to long-term hearing outcomes. There were no significant predictors of
      long-term successful graft outcomes. Mastoidectomy was not a significant factor
      predicting long-term outcomes. Our long-term outcomes showed that mastoidectomy
      can be an avoidable surgical procedure in tympanoplasty for perforated COM, even
      if the ear is infected.

PMID- 18807058
TI  - Effect of cochlear implantation on horizontal semicircular canal function.
AB  - The objective of this study was to assess the influence of a cochlear implant
      (CI) on horizontal semicircular canal (hSCC) function, to test the correlation
      with symptomatic vertigo and to identify possible risk factors for a
      postoperative vestibular impairment. In a prospective observational study design,
      forty-seven adult patients who had undergone cochlear implantation at Cochlear
      Implant Center at a tertiary referral university hospital, Munich, between 2003
      and 2007, were studied. Postoperative vertigo symptoms were assessed using a
      questionnaire followed by a structured interview. Patients were subjected to
      caloric and rotational chair vestibular function tests pre- and postoperatively.
      The CI operation was performed with a retroauricular transmastoidal approach by
      three different surgeons. Thirty-six implants were Cochlear Nucleus 24 devices
      and 11 implants were MedEl devices. Twenty-one (45%) patients reported vertigo
      symptoms after CI. Functional testing of the hSCC yielded valid results in 45 of
      the 47 patients. Thirty-two percent of patients had a substantially reduced hSCC
      function after CI. Responses of caloric irrigation showed a significant worsening
      postoperatively in the CI ears. No direct correlation between a decrease in
      caloric response and risk of postoperative vertigo symptoms could be established.
      For the criteria age, sex, implant type, surgeon, cause of deafness, petrous bone
      CT findings and preoperative vertigo, there were no significant differences
      between the patients with and the patients without postoperative vertigo. Besides
      morphological changes, a cochlear implantation also causes functional damage of
      vestibular parts of the labyrinth. Our study showed a significant worsening of
      the caloric response. However, this alteration did not lead to vertigo complaints
      in all patients. It is therefore presumed that additional damage to sensory or
      visual afferents and central vestibular compensatory mechanisms play a role.

PMID- 18807060
TI  - Authors' response to the comments by Eckel on the editorial "The future of the
      TNM staging system in laryngeal cancer: time for a debate?".

PMID- 18807061
TI  - Concerning the editorial "The future of the TNM staging system in laryngeal
      cancer: time for a debate?" by Ferlito and Rinaldo.

PMID- 18807062
TI  - The Stem Cell Network model: clinical implications in cancer.
AB  - This review will discuss the aspects of stem cell biology that can contribute to
      explain tumor development and why standard oncology treatments sometimes fail. We
      also propose an integrated model of tumor progression based on the putative
      occurrence of Stem Cell Networks (SCNs). In a SCN, the somatic stem cells are
      derived from a common embryonic stem cell, share a specific molecular profile and
      maintain a high degree of cell-cycle synchronization. In the study of cancer, the
      SCN model introduces an additional conceptual frame to the interpretation of both
      the cancer stem cell (CSC) hypothesis and the field cancerization concept. The
      CSC model may explain how the cancer fields develop, justifies their sizes and
      shapes, contribute to explain the local recurrences in patients with free
      margins, the second primary tumors, the success of organ preserving surgical
      approaches or the trend of different tumors to metastasize to certain locations.
      We propose that the SCN model of cancer provides some clues for further
      understanding tumor progression and raises promising experimental and clinical
      implications.

PMID- 18807063
TI  - Long-term results with a simple technique of stoma creation after laryngectomy.
AB  - Stomal stenosis after laryngectomy has a major impact on patient rehabilitation.
      The major contributory factor is the operative technique. The goal is to achieve
      a widely patent stoma. The objective of the study was to review the long-term
      results of the technique of stoma creation used by the senior author (CJW). The
      simple technique, using skin triangles for tracheostoma creation after
      laryngectomy, has been used by the senior author for past 6 years. Review of 59
      cases of total laryngectomy with or without partial pharyngectomies in whom this
      technique was used for stomaplasty. The technique described for stoma creation
      after total laryngectomy has been used in 59 patients (48 male, 11 female) over 6
      years. The follow-up of these patients varies from 6 months to 6 years. Of these
      patients 54/59 (91.5%) did not have any problems with the stoma. A total of 5/59
      (8.5%) patients, the stoma was narrow. Amongst these patients with narrow stoma,
      only 1 patient (1.7%) has had dilatation done and the others are managing
      reasonably with a stoma button. None of the patients in this study has required
      revision procedures on the stoma. The simple technique of stoma creation
      described in this study has good long-term results.

PMID- 18807064
TI  - Spiny versus stubby: 3D reconstruction of human myenteric (type I) neurons.
AB  - We have compared the three-dimensional (3D) morphology of stubby and spiny
      neurons derived from the human small intestine. After immunohistochemical triple
      staining for leu-enkephalin (ENK), vasoactive intestinal peptide (VIP) and
      neurofilament (NF), neurons were selected and scanned based on their
      immunoreactivity, whether ENK (stubby) or VIP (spiny). For the 3D reconstruction,
      we focused on confocal data pre-processing with intensity drop correction, non
      blind deconvolution, an additional compression procedure in z-direction, and
      optimizing segmentation reliability. 3D Slicer software enabled a semi-automated
      segmentation based on an objective threshold (interrater and intrarater
      reliability, both 0.99). We found that most dendrites of stubby neurons emerged
      only from the somal circumference, whereas in spiny neurons, they also emerged
      from the luminal somal surface. In most neurons, the nucleus was positioned
      abluminally in its soma. The volumes of spiny neurons were significantly larger
      than those of stubby neurons (total mean of stubbies 806 +/- 128 mum(3), of
      spinies 2,316 +/- 545 mum(3)), and spiny neurons had more dendrites (26.3 vs.
      11.3). The ratios of somal versus dendritic volumes were 1:1.2 in spiny and 1:0.3
      in stubby neurons. In conclusion, 3D reconstruction revealed new differences
      between stubby and spiny neurons and allowed estimations of volumetric data of
      these neuron populations.

PMID- 18807065
TI  - Changes in motor cortex excitability following training of a novel goal-directed
      motor task.
AB  - Training of skilled movements leads to typical changes in motor evoked potentials
      (MEPs). To explore how such changes are related to motor performance and hand
      preference, a goal-directed movement task was implemented on a haptic interface.
      Right and left hands of right-handed subjects were trained in two sessions
      separated by a pause of 10 min. Transcranial magnetic stimulation (TMS) was
      applied contralaterally to the trained hand before and after each session.
      Effects of right hand training: after session #1 MEP-facilitation was +60%,
      intracortical inhibition (ICI) was reduced and task improvement was +37%.
      Following session #2 all variables remained unchanged. Left hand training: after
      session #1 MEP-facilitation was +59%, ICI remained unchanged and task improvement
      was +30%. Following session #2 all variables remained unchanged. It is concluded
      that mainly the early phase of skill acquisition induces neuroplastic changes.
      The asymmetry in ICI obviously reflects functional side differences in hand motor
      control.

PMID- 18807066
TI  - Oscillatory neural network for pattern recognition: trajectory based
      classification and supervised learning.
AB  - Computer algorithms that match human performance in recognizing written text or
      spoken conversation remain elusive. The reasons why the human brain far exceeds
      any existing recognition scheme to date in the ability to generalize and to
      extract invariant characteristics relevant to category matching are not clear.
      However, it has been postulated that the dynamic distribution of brain activity
      (spatiotemporal activation patterns) is the mechanism by which stimuli are
      encoded and matched to categories. This research focuses on supervised learning
      using a trajectory based distance metric for category discrimination in an
      oscillatory neural network model. Classification is accomplished using a
      trajectory based distance metric. Since the distance metric is differentiable, a
      supervised learning algorithm based on gradient descent is demonstrated.
      Classification of spatiotemporal frequency transitions and their relation to a
      priori assessed categories is shown along with the improved classification
      results after supervised training. The results indicate that this spatiotemporal
      representation of stimuli and the associated distance metric is useful for simple
      pattern recognition tasks and that supervised learning improves classification
      results.

PMID- 18807067
TI  - Compartment model of neuropeptide synaptic transport with impulse control.
AB  - In this paper a mathematical description of a presynaptic episode of slow
      synaptic neuropeptide transport is proposed. Two interrelated mathematical
      models, one based on a system of reaction diffusion partial differential
      equations and another one, a compartment type, based on a system of ordinary
      differential equations (ODE) are formulated. Processes of inflow, calcium
      triggered activation, diffusion and release of neuropeptide from large dense core
      vesicles (LDCV) as well as inflow and diffusion of ionic calcium are represented.
      The models assume the space constraints on the motion of inactive LDCVs and free
      diffusion of activated ones and ions of calcium. Numerical simulations for the
      ODE model are presented as well. Additionally, an electronic circuit, reflecting
      the functional properties of the mathematically modelled presynaptic slow
      transport processes, is introduced.

PMID- 18807068
TI  - The signal molecule lysophosphatidylcholine in Eschscholzia californica is
      rapidly metabolized by reacylation.
AB  - In cultured cells of California poppy (Eschscholzia californica),
      lysophosphatidylcholine (LPC) triggers a signal path that finally induces
      alkaloid biosynthesis. LPC is transiently generated by elicitor-activated
      phospholipase A(2) of the plasma membrane. Externally added LPC is rapidly
      acylated by a membrane-bound enzyme that shows the highest specific activity in
      the purified plasma membrane. The fatty acid incorporated into the sn-2 position
      of LPC is preferentially linoleic (18:2), which is the most abundant acyl
      component in the PC species of Eschscholzia cells, but a minor component of the
      pool of free fatty acids. The fatty acid at the sn-1 position of LPC is less
      important for substrate specificity. The capacity of LPC acylation by intact
      cells or isolated plasma membranes by far exceeds the rate of LPC generation by
      activated phospholipase A(2) and is not limited by the availability of acyl
      donors. Metabolites other than phosphatidylcholine (PC) were not significantly
      produced from labeled LPC within 20 min, indicating that lysophospholipases are
      not significantly contributing to the short-time metabolism of LPC. It is
      concluded that reacylation to PC is the dominating process in the detoxication of
      LPC and ensures the transient character of its steady state concentrations, even
      at maximum phospholipase A(2) activities.

PMID- 18807069
TI  - Gene expression changes induced by space flight in single-cells of the fern
      Ceratopteris richardii.
AB  - This work describes a rare high-throughput evaluation of gene expression changes
      induced by space flight in a single plant cell. The cell evaluated is the spore
      of the fern Ceratopteris richardii, which exhibits both perception and response
      to gravity. cDNA microarray and Q RT-PCR analysis of spores germinating in
      microgravity onboard NASA space shuttle flight STS-93 revealed changes in the
      mRNA expression of roughly 5% of genes analyzed. These gene expression changes
      were compared with gene expression changes that occur during gravity perception
      and response in animal cells and multicellular plants. Our data contribute to a
      better understanding of the impact of space flight conditions, including
      microgravity, on cellular growth and development, and provide insights into the
      adaptive strategies of individual cells in response to these conditions.

PMID- 18807070
TI  - Expression of callose synthase genes and its connection with Npr1 signaling
      pathway during pathogen infection.
AB  - Callose synthesis occurs at specific stages of plant cell wall development in all
      cell types, and in response to pathogen attack, wounding and physiological
      stresses. We determined the expression pattern of "upstream regulatory sequence"
      of 12 Arabidopsis callose synthase genes (CalS1-12) genes and demonstrated that
      different callose synthases are expressed specifically in different tissues
      during plant development. That multiple CalS genes are expressed in the same cell
      type suggests the possibility that CalS complex may be constituted by heteromeric
      subunits. Five CalS genes were induced by pathogen (Hyaloperonospora arabidopsis,
      previously known as Peronospora parasitica, the causal agent of downy mildew) or
      salicylic acid (SA), while the other seven CalS genes were not affected by these
      treatments. Among the genes that are induced, CalS1 and CalS12 showed the highest
      responses. In Arabidopsis npr1 mutant, impaired in response of pathogenesis
      related (PR) genes to SA, the induction of CalS1 and CalS12 genes by the SA or
      pathogen treatments was significantly reduced. The patterns of expression of the
      other three CalS genes were not changed significantly in the npr1 mutant. These
      results suggest that the high induction observed of CalS1 and CalS12 is Npr1
      dependent while the weak induction of five CalS genes is Npr1 independent. In a T
      DNA knockout mutant of CalS12, callose encasement around the haustoria on the
      infected leaves was reduced and the mutant was found to be more resistant to
      downy mildew as compared to the wild type plants.

PMID- 18807071
TI  - The invertebrate microtubule-associated protein PTL-1 functions in
      mechanosensation and development in Caenorhabditis elegans.
AB  - PTL-1, a microtubule-associated protein of the structural MAP2/tau family, is the
      sole member of this gene family in Caenorhabditis elegans. Sequence analysis of
      available invertebrate genomes revealed a number of single, putative tau-like
      genes with high similarity to ptl-1. The ptl-1 gene is expressed in a number of
      cells, most notably mechanosensory neurons. We examined the role of ptl-1 in C.
      elegans in adult neurons as well as during development. A ptl-1 knockout strain
      of worms exhibited an egg-hatching defect, as well as a reduced sensitivity to
      touch stimuli. In addition, the knockout allele ptl-1(ok621) acts as a dominant
      enhancer of several temperature-sensitive alleles of mec-7 and mec-12, which code
      the isoforms of beta-tubulin and alpha-tubulin that together form the unusual 15
      protofilament microtubules involved in touch sensation. These results demonstrate
      for the first time a functional role for this microtubule-associated protein in
      nematodes and suggest that PTL-1 is involved in mechanosensation as well as some
      aspect of embryogenesis.

PMID- 18807072
TI  - Exploration of the APC/beta-catenin (WNT) pathway and a histologic classification
      system for pulmonary artery intimal sarcoma. A study of 18 cases.
AB  - APC, a tumor suppressor gene in the Wnt pathway, stabilizes beta-catenin and
      controls cell growth. Mutation of APC or beta-catenin leads to nuclear
      accumulation of beta-catenin and transcription of cyclin D1/cyclin A. Pulmonary
      artery sarcoma (PAS) were studied by morphologic, immunohistochemical, and
      molecular genetic methods of the Wnt pathway. Eighteen cases were included: mean
      age 52 years, primary intraluminal location with typical clinical presentation.
      PAS were classified as epithelioid (n = 4) or malignant fibrous histiocytoma
      (MFH; spindled/pleomorphic, n = 4), myxofibrosarcoma (n = 8), and one each
      hemangiopericytoma-like or malignant inflammatory myofibroblastic tumor-like. The
      tumor cells demonstrated vimentin, focal actins, and rare focal desmin
      positivity. All but one were grade 2 or 3 by FNCLCC grading. Alteration in
      chromosome 5q21 (APC) was found in 4/14 PAS by LOH, mostly epithelioid-type; an
      MFH-type case demonstrated microsatellite instability (MSI) and nuclear beta
      catenin. Cyclin D1 was expressed in seven tumors, all myxofibrosarcoma-type. No
      mutations were detected in APC or beta-catenin. In summary, PAS are predominantly
      intermediate grade myxofibrosarcoma in middle-aged males, and fatal in two-thirds
      of patients. Despite myofibroblastic phenotype, APC/beta-catenin pathway changes
      are rare. Cyclin D1, only expressed in the myxofibrosarcoma-type, is likely
      transcribed via factors other than beta-catenin.

PMID- 18807073
TI  - Molecular basis of ADAMTS13 dysfunction in thrombotic thrombocytopenic purpura.
AB  - Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathic
      disorder characterized by thrombocytopenia, hemolytic anemia, neurological and
      renal manifestations, and fever. It is associated with dysfunctional von
      Willebrand factor (VWF) proteolysis and the occurrence of VWF- and platelet-rich
      thrombi in the microcirculation of multiple organs, including the kidneys. Von
      Willebrand factor is a large glycoprotein that circulates in plasma as a series
      of multimers, and it plays a major role in primary hemostasis by inducing the
      formation of platelet plugs at sites of vascular injury and high-shear stress.
      Its activity is dependent on the sizes of the multimers, with ultra-large (UL)
      VWF multimers being biologically very potent. The ULVWF multimers are rapidly
      degraded upon their secretion from endothelial cells in normal individuals but
      not in the circulation of TTP patients, causing the formation of disseminated
      thrombi in the latter. The defective breakdown of VWF is attributed to a severely
      deficient activity of the VWF-cleaving protease ADAMTS13, a plasma
      metalloprotease synthesized in the liver, kidneys, and endothelium. This protease
      rapidly degrades VWF-platelet strings under flow by proteolytic cleavage of the
      VWF subunit, thereby regulating the size of the platelet thrombus. Congenital TTP
      occurs due to ADAMTS13 mutations, with the usual debut occurring during the first
      years of life, while acquired TTP is associated with auto-antibodies against
      ADAMTS13.

PMID- 18807074
TI  - Peritoneal dialysis prescription in children: bedside principles for optimal
      practice.
AB  - There is no unique optimal peritoneal dialysis prescription for all children,
      although the goals of ultrafiltration and blood purification are universal. In
      turn, a better understanding of the physiology of the peritoneal membrane, as a
      dynamic dialysis membrane with an exchange surface area recruitment capacity and
      unique permeability characteristics, results in the transition from an empirical
      prescription process based on clinical experience alone to the potential for a
      personalized prescription with individually adapted fill volumes and dwell times.
      In all cases, the prescribed exchange fill volume should be scaled for body
      surface area (ml/m(2)), and volume enhancement should be conducted based on
      clinical tolerance and intraperitoneal pressure measurements (IPP; cmH(2)O). The
      exchange dwell times should be determined individually and adapted to the needs
      of the patient, with particular attention to phosphate clearance and
      ultrafiltration capacity. The evolution of residual kidney function and the
      availability of new, more physiologic, peritoneal dialysis fluids (PDFs) also
      influence the prescription process. An understanding of all of these principles
      is integral to the provision of clinically optimal PD.

PMID- 18807075
TI  - Changes in sleep patterns during prolonged stays in Antarctica.
AB  - Various countries have permanent research bases in Antarctica that are manned
      year-round by a few members of an expedition team, facing extremes of temperature
      with the associated hardships. Acclimatisation to such an environment is
      associated with pyschophysiological changes along with alterations in sleep
      patterns. The present study was undertaken to explore the changes in sleep
      patterns of six members of the Indian expedition team during their winter stay at
      Maitri, the permanent research station of India in Antarctica. The mean (+/- SEM)
      age, height and weight of the subjects were 35.7 +/- 2.32 years, 168.3 +/- 2.37
      cm and 71.0 +/- 1.88 kg, respectively. Polysomnographic sleep recordings were
      obtained as baseline data in November 2004 in Delhi (altitude 260 m, latitude 29
      degrees N, longitude 77 degrees E); data on the same parameters were collected at
      Maitri, Antarctica (altitude 120 m, latitude 70 degrees 45' 39'' S, longitude 11
      degrees 44' 49'' E) from January to December 2005. A one-way analysis of variance
      with repeated measures showed a significant variation with time (month effect) in
      most of the sleep parameters recorded. Total sleep time decreased from Delhi
      baseline values in all months, sleep efficiency decreased significantly during
      winter months, duration of waking period after sleep onset increased
      significantly in winter, sleep latency increased immediately after exposure in
      January, stages 3 and 4 (slow wave sleep) reduced during dark winter months,
      whereas stages 1 and 2 and rapid eye movement sleep increased during dark winter
      months. This study observed a prevailing general trend of sleep disturbances
      amongst overwintering members in a modern Antarctic station.

PMID- 18807076
TI  - A two-concentric-loop iterative method in estimation of displacement height and
      roughness length for momentum and sensible heat.
AB  - A two-concentric-loop iterative (TCLI) method is proposed to estimate the
      displacement height and roughness length for momentum and sensible heat by using
      the measurements of wind speed and air temperature at two heights, sensible heat
      flux above the crop canopy, and the surface temperature of the canopy. This
      method is deduced theoretically from existing formulae and equations. The main
      advantage of this method is that data measured not only under near neutral
      conditions, but also under unstable and slightly stable conditions can be used to
      calculate the scaling parameters. Based on the data measured above an Acacia
      Saligna agroforestry system, the displacement height (d0) calculated by the TCLI
      method and by a conventional method are compared. Under strict neutral
      conditions, the two methods give almost the same results. Under unstable
      conditions, d0 values calculated by the conventional method are systematically
      lower than those calculated by the TCLI method, with the latter exhibiting only
      slightly lower values than those seen under strictly neutral conditions.
      Computation of the average values of the scaling parameters for the agroforestry
      system showed that the displacement height and roughness length for momentum are
      68% and 9.4% of the average height of the tree canopy, respectively, which are
      similar to percentages found in the literature. The calculated roughness length
      for sensible heat is 6.4% of the average height of the tree canopy, a little
      higher than the percentages documented in the literature. When wind direction was
      aligned within 5 degrees of the row direction of the trees, the average
      displacement height calculated was about 0.6 m lower than when the wind blew
      across the row direction. This difference was statistically significant at the
      0.0005 probability level. This implies that when the wind blows parallel to the
      row direction, the logarithmic profile of wind speed is shifted lower to the
      ground, so that, at a given height, the wind speeds are faster than when the wind
      blows perpendicular to the row direction.

PMID- 18807077
TI  - Kidney damage in extracorporeal shock wave lithotripsy: a numerical approach for
      different shock profiles.
AB  - In shock-wave lithotripsy--a medical procedure to fragment kidney stones--the
      patient is subjected to hypersonic waves focused at the kidney stone. Although
      this procedure is widely applied, the physics behind this medical treatment, in
      particular the question of how the injuries to the surrounding kidney tissue
      arise, is still under investigation. To contribute to the solution of this
      problem, two- and three-dimensional numerical simulations of a human kidney under
      shock-wave loading are presented. For this purpose a constitutive model of the
      bio-mechanical system kidney is introduced, which is able to map large visco
      elastic deformations and, in particular, material damage. The specific phenomena
      of cavitation induced oscillating bubbles is modeled here as an evolution of
      spherical pores within the soft kidney tissue. By means of large scale finite
      element simulations, we study the shock-wave propagation into the kidney tissue,
      adapt unknown material parameters and analyze the resulting stress states. The
      simulations predict localized damage in the human kidney in the same regions as
      observed in animal experiments. Furthermore, the numerical results suggest that
      in first instance the pressure amplitude of the shock wave impulse (and not so
      much its exact time-pressure profile) is responsible for damaging the kidney
      tissue.

PMID- 18807078
TI  - Quantitative in vivo 1H spectroscopic imaging of metabolites in the early
      postnatal mouse brain at 17.6 T.
AB  - OBJECT: Early postnatal brain maturation is closely connected to local changes of
      metabolite levels. Spatially resolved in vivo (1)H NMR spectroscopic imaging is
      applied to follow absolute changes of brain metabolites in early postnatal mouse
      brain. MATERIALS AND METHODS: A short echo time semi LASER (localization by
      adiabatic selective refocusing) chemical shift imaging (CSI) sequence
      incorporating weighted k-space averaging was implemented at high magnetic field
      (17.6 T). In vivo measurements were carried out on postnatal days 5, 8, 12, 16,
      and 20. In vivo relaxation times T (1) and T (2) were measured using variable
      repetition times or a CPMG sequence, respectively, combined with LASER single
      voxel localization. RESULTS: Spectra were obtained with a spatial resolution of
      (1 x 1) mm(2) in a 1.5 mm slice as early as postnatal day 5. Maturational changes
      of absolute metabolite concentrations of major metabolites were calculated in
      four different brain regions. A significant increase of N-acetylaspartate (NAA),
      total creatine (tCr), and glutamate/glutamine (Glx) concentration was paralleled
      by a decrease of taurine (Tau) concentration with age (P < 0.05). Differences
      between brain regions were found for NAA, tCr, and Tau (P < 0.05). Furthermore,
      in vivo T (1) and T (2) of the four major brain metabolites in adult mice are
      reported. CONCLUSION: The implemented semi LASER CSI sequence allows following
      regional changes of metabolite levels. It is suitable for investigation of local
      differences in brain metabolism and development.

PMID- 18807079
TI  - Pulse transit time for scoring subcortical arousal in infants with obstructive
      sleep apnea.
AB  - INTRODUCTION: An altered autonomic control and response to respiratory events
      during sleep have been reported in infants with obstructive sleep apnea but
      appropriate methods are not established. We assessed the feasibility of pulse
      transit time (PTT) in detecting subcortical arousals in eight infants (median age
      7 days) suffering from the Pierre Robin sequence and obstructive sleep apnea.
      METHODS: Sleep studies including recordings of PTT performed before and after
      successful orthodontic treatment for their OSA were analyzed. PTT arousals (i.e.,
      fall in PTT by > or =15 ms lasting for > or =3 s) were visually scored using
      specific analysis software. Apnea-related PTT arousals and spontaneous PTT
      arousals were distinguished and predicting factors for the occurrence of
      uninterpretable PTT signal and PTT arousals were analyzed. RESULTS: Six-hundred
      and seven apneas were analyzed. Uninterpretable PTT signal appeared in 394 (65%)
      apneas and were due to a disturbed pulse waveform in 63%. Predictors for the
      occurrence of uninterpretable PTT signal were type of apnea (odds ratio, 95%
      confidence interval for obstructive apnea = 0.5, 0.4-0.9) and duration of apnea
      (odds ratio, 95% confidence interval per second duration = 1.4, 1.3-1.5). Of 213
      apneas with interpretable PTT signal, 43 (7% of all apneas) were followed by a
      PTT arousal. Predictor for their occurrence was treatment status (odds ratio, 95%
      confidence interval for pre-treatment status = 3.4, 1.3-8.8). Spontaneous PTT
      arousals during control periods appeared more frequently pre-treatment compared
      to post-treatment (41% vs. 16%; p-value = 0.001). There were only weak
      correlations between changes in PTT, heart rate, and arterial oxygen saturation
      (correlation coefficient <0.3). CONCLUSION: The feasibility of PTT in scoring
      apnea-related subcortical arousals in infants may be questionable. However,
      scoring spontaneous PTT arousals may be an approach for assessing sleep
      disruption in infants with obstructive sleep apnea.

PMID- 18807080
TI  - Opioid-associated central sleep apnea: a case series.
AB  - INTRODUCTION: Subjects on methadone maintenance for drug addiction have been
      reported to have central sleep apnea (CSA). However, there are few reports of
      disordered breathing in patients receiving opioids for chronic pain. MATERIALS
      AND METHODS: We report on six patients (ages 41-68, two females, body mass index
      27-34, morphine equivalent doses 120-420 mg/day, Epworth Scales 7-21) referred to
      our sleep center receiving sustained release opioids for more than 6 months with
      excessive daytime sleepiness. CSA was defined as apnea-hypopnea index (AHI) more
      than 5 per hour with > or =50% central events. Bilevel (BLV) titration was done
      to determine settings and all patients were followed for at least 6 months on
      nocturnal BLV. AHI ranged 28.4-106 per hour. Time less than 90% O(2) saturation
      ranged 1.8 min to 6.4 h. Four of the patients were treated with chronic BLV
      ventilation with settings ranging 12-16 cm H(2)O (inspiratory positive airway
      pressure)/4-8 cm H(2)O (expiratory positive airway pressure) with backup rate of
      12-16. Among the four patients who used BLV treatment for at least 6 months,
      Epworth scores improved (by 4, 12, 5, and 9, respectively). CONCLUSION: Treatment
      of opioid-associated CSA with BLV corrected nocturnal hypoxemia and reduced sleep
      fragmentation. Randomized controlled trials, with objective measures of daytime
      function, are recommended in opioid-induced CSA patients.

PMID- 18807081
TI  - Risk for sleep apnea syndrome in Pakistan: a cross-sectional survey utilizing the
      Berlin questionnaire.
AB  - PURPOSE: The purpose of this study was to assess the prevalence of individuals at
      high risk for developing obstructive sleep apnea in the Pakistani population
      using a validated questionnaire. MATERIALS AND METHODS: This is a cross-sectional
      survey using a pre-validated, interviewer-administered questionnaire conducted at
      the Aga Khan University Hospital. All healthy individuals above 18 years of age
      attending a seminar were included as participants after consent. RESULTS: The
      percentage of people in the high-risk group was calculated to be 12.4% out of a
      population of 137. Presence of snoring, hypertension, and body mass index >27.5
      kg/m(2) was found to be more prevalent in high-risk individuals. CONCLUSIONS: A
      significant proportion of the population is at high risk for obstructive sleep
      apnea syndrome.

PMID- 18807082
TI  - Prevalence and risk factors for sleep disordered breathing in a Puerto Rican
      middle-aged population.
AB  - BACKGROUND: The Berlin Questionnaire [an outcome of a primary care physicians'
      conference held in Berlin, Germany, in 1996 that was created to identify patients
      at high risk for sleep disordered breathing (SDB)] was administered to a
      representative sample of middle-age population in Puerto Rico in order to
      document the prevalence of SDB and its associated risk factors. MATERIALS AND
      METHODS: The island was divided in six regions to maintain heterogeneity and to
      have a representative sample of the population per region. Puerto Rican subjects
      between 30-60 years old were recruited in shopping malls, and questionnaires were
      filled. For each subject, body weight, neck circumference, and height were
      measured. Information regarding the diagnosis of hypertension was based upon a
      positive or negative response from study subject in a questionnaire. Data was
      collected for 6 months. RESULTS: A total of 290 subjects, all of Puerto Rican
      origin, were interviewed. Fifty-eight percent of the evaluated sample was found
      at high risk of SDB. Being male, hypertensive, and obese were the strongest risk
      factors for the development of SDB. In women, a neck size above 15 cm was a
      significant risk factor. CONCLUSIONS: This is the first time a prevalence study
      for SDB is done among a representative sample of subjects of Puerto Rican origin.
      It is the first step in documenting how SDB affects this ethnic group.

PMID- 18807083
TI  - Nutritional value of various ray fish liver oils to the pacific white shrimp
      Litopenaeus vannamei.
AB  - A 32-day comparative feeding trial was performed to evaluate the nutritional
      value of four different ray fish liver oils to the Pacific white shrimp
      Litopenaeus vannamei. Four feeds were prepared with liver oil extracted from
      Dasyatis brevis, Rhinoptera steindachneri, Aetobatus narinari, and R. bonasus. A
      control feed was prepared with Menhaden fish oil. Ray fish liver oils were mainly
      composed of poly- and highly unsaturated fatty acids and contained levels of
      20:5n-3 and 22:6n-3 comparable in magnitude to those of Menhaden fish oil, except
      for A. narinari liver oil, which had moderately low concentrations of 20:5n-3 and
      22:6n-3 but showed a particularly high level of 20:4n-6, more than six times
      greater than that of Menhaden fish oil. Dietary fatty acids significantly
      influenced the fatty acid composition of shrimp muscle tissue, e.g., the diet
      with Menhaden fish oil elicited significantly higher shrimp muscle DHA level than
      diets with oil from D. brevis, and A. narinari, but not than diets with oil from
      R. steindachneri and R. bonasus. In spite of these differences, all four ray fish
      liver oils evaluated were as efficient in promoting growth and survival of L.
      vannamei as Menhaden fish oil, an ingredient known for its adequate nutritional
      quality to shrimp and fish. This study demonstrated one of the many possible
      applications of a locally-available resource that is currently being wasted.

PMID- 18807084
TI  - Distinct lipid rafts in subdomains from human placental apical
      syncytiotrophoblast membranes.
AB  - We report on the characteristics of raft domains in the apical membrane from
      human placental syncytiotrophoblast (hSTB), an epithelium responsible for
      maternal-fetal exchange. Previously, we described two isolated fractions of the
      hSTB apical membrane: a classical microvillous membrane (MVM) and a light
      microvillous membrane (LMVM). Detergent-resistant microdomains (DRMs) from MVM
      and LMVM were prepared with Triton X-100 followed by flotation in a sucrose
      gradient and tested by Western and dot blot with raft markers (placental alkaline
      phosphatase, lipid ganglioside, annexin 2) and transferrin receptor as a nonraft
      marker. DRMs from both fractions showed a consistent peak for these markers,
      except that the DRMs from MVM had no annexin 2 mark. Cholesterol depletion
      modified the segregation in both groups of DRMs. Our results show two
      distinguishable lipid raft subsets from MVM and LMVM. Additionally, we found
      significant differences between MVM and LMVM in cholesterol content and in
      expression of cytoskeletal proteins. MVM is enriched in ezrin and beta-actin; in
      contrast, cholesterol and cytokeratin-7 are more abundant in LMVM. These
      differences may explain the distinct properties of the lipid raft subtypes.

PMID- 18807085
TI  - Kinetic analysis of permeation of mitochondria-targeted antioxidants across
      bilayer lipid membranes.
AB  - Mitochondria-targeted antioxidants consisting of a quinone part conjugated with a
      lipophilic cation via a hydrocarbon linker were previously shown to prevent
      oxidative damage to mitochondria in vitro and in vivo. In the present work, we
      studied the permeation of a series of compounds of this type across a planar
      bilayer phospholipid membrane. For this purpose, relaxation of the electrical
      current after a voltage jump was measured. With respect to the characteristic
      time of the relaxation process reflecting the permeation rate, hydrophobic
      cations can be ranked in the following series: 10(plastoquinonyl) decylrhodamine
      19 (SkQR1) > 10-(6'-plastoquinonyl) decyltriphenylphosphonium (SkQ1) > 10-(6'
      methylplastoquinonyl) decyltriphenylphosphonium (SkQ3) > 10-(6'-ubiquinonyl)
      decyltriphenylphosphonium (MitoQ). Thus, the permeation rate increased with (1)
      an increase in the size of the hydrophobic cation and (2) an increase in
      hydrophobicity of the quinone moiety. SkQ1 containing plastoquinone was shown to
      be more permeable through the membrane compared to MitoQ containing ubiquinone,
      which might be the reason for more pronounced beneficial action of SkQ1 in vitro
      and in vivo. The above approach can be recommended for the search for new
      antioxidants or other compounds targeted to mitochondria.

PMID- 18807086
TI  - Our evolving knowledge of the transcriptional landscape.
AB  - The development of a genome-scale approach to identification of the 5' ends of
      capped mRNAs (CAGE) has given new insights into many aspects of mammalian
      RNApolII transcription control. They include the identification of the minimal
      initiator motif, the different types of proximal promoter architecture, the
      promoters of noncoding RNAs, the transcription of retrotransposons, and the
      extensive impact of alternative promoters on the proteome. CAGE also offers
      applications as a form of expression profiling that measures promoter use,
      allowing more precise development of transcriptional network models.

PMID- 18807087
TI  - Biomarkers of systemic inflammation in stable and exacerbation phases of COPD.
AB  - Apart from the deleterious effects on the lungs, chronic obstructive pulmonary
      disease (COPD) should be considered a complex, systemic disease involving several
      organs and systems. The nature and course of systemic inflammation in COPD is
      important since there is a potential for anti-inflammatory therapy. The objective
      of the current study was to assess biomarkers of systemic inflammation in stable
      and exacerbation phases of COPD patients as compared to healthy controls. We also
      investigated the course of these biomarkers after COPD exacerbation to evaluate
      their usefulness for disease monitoring. Eighty-three stable patients with
      moderate to very severe COPD, 20 patients in exacerbation phase, and 30 subjects
      with normal pulmonary function were included. Serum tumor necrosis factor-alpha
      (TNF-alpha), interleukin-6 (IL-6), and nitric oxide (NO) levels were measured
      once in stable COPD patients and controls and three times in the COPD
      exacerbation group during follow-up. TNF-alpha and IL-6 levels were higher than
      in controls in both stable and exacerbation groups. Although NO was not higher in
      the stable COPD group than in controls, it was higher in the exacerbation group.
      In follow-up after the exacerbation period, significant alteration was not
      detected in cytokine or NO levels compared to admission. Raised serum levels of
      TNF-alpha and IL-6 support their use as biomarkers of the systemic inflammatory
      response in stable COPD patients. However, the circulating biomarkers we have
      studied are not found to be useful either as indicators of COPD exacerbation or
      for monitoring recovery after exacerbation.

PMID- 18807088
TI  - A highly thermosensitive and permeable mutant of the marine yeast Cryptococcus
      aureus G7a potentially useful for single-cell protein production and its
      nutritive components.
AB  - The highly thermosensitive and permeable mutants are the mutants from which
      intracellular contents including proteins can be released when they are incubated
      both in the low osmolarity water and at the nonpermissive temperature (usually 37
      degrees C). After mutagenesis by using nitrosoguanidine, a highly thermosensitive
      and permeable mutant named Z114 was obtained from the marine yeast Cryptococcus
      aureus G7a. Of the total protein, 65.3% was released from the mutant cells
      suspended in distilled water after they were treated at 37 degrees C overnight.
      However, only 12.3% of the total protein was released from the mutant cells
      suspended in 1.0 M sorbitol solution after they were treated at 37 degrees C
      overnight. We found that intracellular density of the mutant treated at 37
      degrees C was greatly decreased, and cell volume of the mutant treated at 37
      degrees C was increased due to the increased protein release. However, no
      significant changes in the intracellular density and cell volume of the mutant
      were observed when its cells suspended in 1.0 M sorbitol solution were treated at
      37 degrees C. It was found that no big changes in cell growth, protein content,
      vitamin C content, nucleic acid content, fatty acids, and amino acid compositions
      of both the mutant and its wild type were detected. Therefore, the highly
      thermosensitive and permeable mutant still can be a good candidate as single-cell
      protein. This means that the method used in this study is a simple and efficient
      way to release protein from the highly thermosensitive and permeable yeast mutant
      cells with high protein content.

PMID- 18807089
TI  - Chytridiomycosis and amphibian population declines continue to spread eastward in
      Panama.
AB  - Chytridiomycosis is a globally emerging disease of amphibians and the leading
      cause of population declines and extirpations at species-diverse montane sites in
      Central America. We continued long-term monitoring efforts for the presence of
      the fungal pathogen Batrachochytrium dendrobatidis (Bd) and for amphibian
      populations at two sites in western Panama, and we began monitoring at three new
      sites to the east. Population declines associated with chytridiomycosis emergence
      were detected at Altos de Campana National Park. We also detected Bd in three
      species east of the Panama Canal at Soberania National Park, and prevalence data
      suggests that Bd may be enzootic in the lowlands of the park. However, no
      infected frogs were found further east at Torti (prevalence <7.5% with 95%
      confidence). Our results suggest that Panama's diverse and not fully described
      amphibian communities east of the canal are at risk. Precise predictions of
      future disease emergence events are not possible until factors underlying disease
      emergence, such as dispersal, are understood. However, if the fungal pathogen
      spreads in a pattern consistent with previous disease events in Panama, then
      detection of Bd at Torti and other areas east of the Panama Canal is imminent.
      Therefore, development of new management strategies and increased precautions for
      tourism, recreation, and biology are urgently needed.

PMID- 18807090
TI  - Disturbed XIAP and XAF1 expression balance is an independent prognostic factor in
      gastric adenocarcinomas.
AB  - BACKGROUND: Dysregulation of apoptosis is a key factor in carcinogenesis and
      tumor progression. X-linked inhibitor of apoptosis (XIAP) is the most potent
      member of the inhibitor of apoptosis protein (IAP) family, which directly
      inhibits apoptosis by binding to caspases. Antagonists of XIAP have recently been
      identified: second mitochondria-derived activator of caspase/direct IAP-binding
      protein with low PI (Smac/DIABLO) and XIAP-associated factor 1 (XAF1). However,
      little research has been conducted on the association between gastric cancer
      survival and the mechanism of apoptosis involving XIAP and its antagonists,
      Smac/DIABLO and XAF1. METHODS: XIAP, Smac/DIABLO, and XAF1 expression was
      analyzed by immunohistochemistry (IHC) in 187 gastric adenocarcinomas.
      Correlations between XIAP, Smac/DIABLO or XAF1 expression and clinicopathological
      factors were analyzed. Disease-specific survival after surgery was examined.
      RESULTS: Of 187 samples, XIAP was overexpressed in 140, Smac was overexpressed in
      117, and XAF1 was overexpressed in 106. Individually, XIAP, Smac, and XAF1 were
      not significantly associated with disease-specific survival. However, patients
      showing high expression of XIAP and low expression of XAF1 had significantly
      poorer survival when compared with other groups (P = 0.024). CONCLUSION: The
      expression balance of XIAP and XAF1 is an independent prognostic factor in
      gastric adenocarcinoma.

PMID- 18807091
TI  - Inflammatory breast cancer after neoadjuvant chemotherapy: can magnetic resonance
      imaging precisely diagnose the final pathological response?

PMID- 18807092
TI  - End-of-skin grafts in syndactyly release: description of a new flap for web space
      resurfacing and primary closure of finger defects.
AB  - Treatment of syndactyly necessitates creation of neo-web space and separation of
      fingers. Traditionally, this has been done by use of flaps taken from the dorsum;
      the resultant raw areas thus created have been managed by use of skin grafts. The
      classical teaching has been that the separated fingers will need skin graft as
      primary closure is not possible. The skin grafts have a tendency to contract and
      lead to finger flexion contractures and "creep" of the web space. We describe a
      flap based upon subcutaneous tissue in the web that is moved in a V-Y fashion to
      resurface the neo-web. The flap donor site can easily be closed primarily. The
      fingers are then separated; the subcutaneous fat is carefully removed from the
      finger flaps under magnification to allow primary closure of the finger defects.
      It has been possible to primarily close the donor site and fingers in all the
      patients. The procedure has been used in seven patients with 14 web releases. The
      age varied between 10 months to 3 years. The V-Y advancement flap based upon the
      subcutaneous pedicle in the region of the web allows adequate creation of a new
      web space. The careful de-fattening of skin flaps allows the separated fingers to
      be closed primarily.

PMID- 18807093
TI  - Selection of operative procedures for cubital tunnel syndrome.
AB  - The purpose of this study was to investigate the primary operative procedures
      that are performed by hand surgeons for cubital tunnel syndrome and their
      reported satisfaction with these procedures. The survey consisted of 22 questions
      regarding primary operative treatment of cubital tunnel syndrome and demographics
      and was sent by email to the 459 active members of the American Association for
      Hand Surgery. One hundred sixty-four surgeons completed the survey (36% response
      rate). The total sample included 154 hand surgeons (143 males, 11 females) who
      operated on cubital tunnel syndrome and the majority of surgeons were in private
      practice (n = 100) followed by academic practice (n = 50). The most prevalent
      factors that influence the decision to operate include evidence of muscle atrophy
      (84%), abnormal nerve conduction studies (51%), and failed non-operative
      treatment (49%). Most surgeons (n = 133) reported using more than one operative
      procedure for their patients with cubital tunnel syndrome. Factors that
      influenced the operative procedure selected included the degree of nerve
      compression (60%), medical comorbidities (30%), patient's occupation (28%), and
      obesity (22%). Following carpal tunnel surgery, 88% of the surgeons were "very
      satisfied" with their patient outcome and following surgery for cubital tunnel
      syndrome, only 44% were "very satisfied" with their patient outcome. Most
      surgeons use more than one operative procedure in their treatment of patients
      with cubital tunnel syndrome and the selection of the operative procedure is
      influenced by patient factors and surgeon preference.

PMID- 18807094
TI  - Tumoral calcinosis--or is it? A case report and review.
AB  - Tumoral calcinosis is an uncommon lesion, composed of ectopic calcified tissue,
      most commonly seen in the large joints of the hips, shoulders, and elbows, but
      may involve the hand and wrist. Patients will often present with localized
      swelling and reduced mobility around the involved joints. Pain is inconsistent
      when presenting in the hands or wrists, but the lesions may interfere with daily
      activities. Multiple variations of the process have been described, ranging from
      those with no definable etiology (primary), to those associated with disorders
      (secondary) such as renal insufficiency, hyperparathyroidism, or hypervitaminosis
      D. The original description of tumoral calcinosis, however, is the familial or
      hereditary type. Treatment of this process involves optimizing the underlying
      physiology and complete surgical excision for symptomatic cases.

PMID- 18807095
TI  - Motor nerve transfers to restore extrinsic median nerve function: case report.
AB  - Active pronation is important for many activities of daily living. Loss of median
      nerve function including pronation is a rare sequela of humerus fracture. Tendon
      transfers to restore pronation are reserved for the obstetrical brachial plexus
      palsy patient. Transfer of expendable motor nerves is a treatment modality that
      can be used to restore active pronation. Nerve transfers are advantageous in that
      they do not require prolonged immobilization postoperatively, avoid operating
      within the zone of injury, reinnervate muscles in their native location prior to
      degeneration of the motor end plates, and result in minimal donor deficit. We
      report a case of lost median nerve function after a humerus fracture. Pronation
      was restored with transfer of the extensor carpi radialis brevis branch of the
      radial nerve to the pronator teres branch of the median nerve. Anterior
      interosseous nerve function was restored with transfer of the supinator branch to
      the anterior interosseous nerve. Clinically evident motor function was seen at 4
      months postoperatively and continued to improve for the following 18 months. The
      patient has 4+/5 pronator teres, 4+/5 flexor pollicis longus, and 4-/5 index
      finger flexor digitorum profundus function. The transfer of the extensor carpi
      radialis brevis branch of the radial nerve to the pronator teres and supinator
      branch of the radial nerve to the anterior interosseous nerve is a novel,
      previously unreported method to restore extrinsic median nerve function.

PMID- 18807096
TI  - Factors associated with intern fatigue.
AB  - BACKGROUND: Prior data suggest that fatigue adversely affects patient safety and
      resident well-being. ACGME duty hour limitations were intended, in part, to
      reduce resident fatigue, but the factors that affect intern fatigue are unknown.
      OBJECTIVE: To identify factors associated with intern fatigue following
      implementation of duty hour limitations. DESIGN: Cross-sectional confidential
      survey of validated questions related to fatigue, sleep, and stress, as well as
      author-developed teamwork questions. SUBJECTS: Interns in cognitive specialties
      at the University of California, San Francisco. MEASUREMENTS: Univariate
      statistics characterized the distribution of responses. Pearson correlations
      elucidated bivariate relationships between fatigue and other variables.
      Multivariate linear regression models identified factors independently associated
      with fatigue, sleep, and stress. RESULTS: Of 111 eligible interns, 66 responded
      (59%). In a regression analysis including gender, hours worked in the previous
      week, sleep quality, perceived stress, and teamwork, only poorer quality of sleep
      and greater perceived stress were significantly associated with fatigue (p <
      0.001 and p = 0.02, respectively). To identify factors that may affect sleep,
      specifically duty hours and stress, a secondary model was constructed. Only
      greater perceived stress was significantly associated with diminished sleep
      quality (p = 0.04), and only poorer teamwork was significantly associated with
      perceived stress (p < 0.001). Working >80 h was not significantly associated with
      perceived stress, quality of sleep, or fatigue. CONCLUSIONS: Simply decreasing
      the number of duty hours may be insufficient to reduce intern fatigue. Residency
      programs may need to incorporate programmatic changes to reduce stress, improve
      sleep quality, and foster teamwork in order to decrease intern fatigue and its
      deleterious consequences.

PMID- 18807097
TI  - Living with hepatitis C: qualitative interviews with hepatitis C-infected
      veterans.
AB  - BACKGROUND: Chronic hepatitis C (HCV) infection affects millions of people in the
      USA and prevalence rates are higher in US veterans. The consequences of HCV
      infection include reduced quality of life, liver damage, and reduced longevity.
      OBJECTIVE: Our objective was to describe the experiences of US veterans living
      with chronic HCV infection and use this information in the development of an HCV
      self-management intervention. METHODS: Twenty-two male HCV-infected veterans
      completed qualitative interviews. Participants were recruited via flyers and
      hepatitis C clinic providers at a major VA medical center. Participants were
      asked about their medical history, being diagnosed with HCV, and general
      experiences living with HCV. RESULTS: The study gathered the following findings:
      the impact of HCV on interpersonal relationships was pronounced, recovery from
      substance use disorders and getting care for HCV were connected, receiving the
      HCV diagnosis was more troubling to non-IV drug users, participants had
      misconceptions about HCV and its treatment, psychological problems were prevalent
      as were barriers to participating in antiviral treatment and HCV care in general.
      CONCLUSION: The themes derived from our analysis indicate that affected veterans
      may benefit from interventions or support to improve HCV-related health
      education, social/relationship issues, psychological issues, and exploration of
      the connection between substance use recovery and motivation to get care for HCV
      infection.

PMID- 18807098
TI  - Periodontal disease and coronary heart disease incidence: a systematic review and
      meta-analysis.
AB  - BACKGROUND: Periodontal disease is common among adults in the US and is a
      potential source of chronic inflammation. Recent data have suggested an important
      role for chronic inflammation in the development of coronary heart disease (CHD).
      OBJECTIVE: To aid the United States Preventive Services Task Force (USPSTF) in
      evaluating whether periodontal disease is an independent novel risk factor for
      incident CHD. METHODS: Studies were identified by searching Medline (1966 through
      March 2008) and reviewing prior systematic reviews, reference lists, and
      consulting experts. Prospective cohort studies that assessed periodontal disease,
      Framingham risk factors, and coronary heart disease incidence in the general
      adult population without known CHD were reviewed and quality rated using criteria
      developed by the USPSTF. Meta-analysis of good and fair quality studies was
      conducted to determine summary estimates of the risk of CHD events associated
      with various categories of periodontal disease. RESULTS: We identified seven
      articles of good or fair quality from seven cohorts. Several studies found
      periodontal disease to be independently associated with increased risk of CHD.
      Summary relative risk estimates for different categories of periodontal disease
      (including periodontitis, tooth loss, gingivitis, and bone loss) ranged from 1.24
      (95% CI 1.01-1.51) to 1.34 (95% CI 1.10-1.63). Risk estimates were similar in
      subgroup analyses by gender, outcome, study quality, and method of periodontal
      disease assessment. CONCLUSION: Periodontal disease is a risk factor or marker
      for CHD that is independent of traditional CHD risk factors, including
      socioeconomic status. Further research in this important area of public health is
      warranted.

PMID- 18807099
TI  - Personal characteristics associated with resident physicians' self perceptions of
      preparedness to deliver cross-cultural care.
AB  - BACKGROUND: Recent reports from the Institute of Medicine emphasize patient
      centered care and cross-cultural training as a means of improving the quality of
      medical care and eliminating racial and ethnic disparities. OBJECTIVE: To
      determine whether, controlling for training received in medical school or during
      residency, resident physician socio-cultural characteristics influence self
      perceived preparedness and skill in delivering cross-cultural care. DESIGN:
      National survey of resident physicians. PARTICIPANTS: A probability sample of
      residents in seven specialties in their final year of training at US academic
      health centers. MEASUREMENT: Nine resident characteristics were analyzed.
      Differences in preparedness and skill were assessed using the chi(2) statistic
      and multivariate logistic regression. RESULTS: Fifty-eight percent (2047/3500) of
      residents responded. The most important factor associated with improved perceived
      skill level in performing selected tasks or services believed to be useful in
      treating culturally diverse patients was having received cross-cultural skills
      training during residency (OR range 1.71-4.22). Compared with white residents,
      African American physicians felt more prepared to deal with patients with
      distrust in the US healthcare system (OR 1.63) and with racial or ethnic
      minorities (OR 1.61), Latinos reported feeling more prepared to deal with new
      immigrants (OR 1.88) and Asians reported feeling more prepared to deal with
      patients with health beliefs at odds with Western medicine (1.43). CONCLUSIONS:
      Cross-cultural care skills training is associated with increased self-perceived
      preparedness to care for diverse patient populations providing support for the
      importance of such training in graduate medical education. In addition, selected
      resident characteristics are associated with being more or less prepared for
      different aspects of cross-cultural care. This underscores the need to both
      include medical residents from diverse backgrounds in all training programs and
      tailor such programs to individual resident needs in order to maximize the
      chances that such training is likely to have an impact on the quality of care.

PMID- 18807100
TI  - Effect of intraluminal pillars on particle motion in bifurcated microchannels.
AB  - A central feature of intussusceptive angiogenesis is the development of an
      intravascular pillar that bridges the opposing sides of the microvessel lumen. In
      this report, we created polydimethyl siloxane (PDMS) microchannels with geometric
      proportions based on corrosion casts of the colon microcirculation. The structure
      of the PDMS microchannels was a bifurcated channel with an intraluminal pillar in
      the geometric center of the bifurcation. The effect of the intraluminal pillar on
      particle flow paths was investigated using an in vitro perfusion system. The
      microchannels were perfused with fluorescent particles, and the particle
      movements were recorded using fluorescence videomicroscopy. We found that the
      presence of an intravascular pillar significantly decreased particle velocity in
      the bifurcation system (p < 0.05). In addition, the pillar altered the trajectory
      of particles in the center line of the flow stream. The particle trajectory
      resulted in prolonged pillar contact as well as increased residence time within
      the bifurcation system (p < 0.001). Our results suggest that the intravascular
      pillar not only provides a mechanism of increasing resistance to blood flow but
      may also participate in spatial redistribution of cells within the flow stream.

PMID- 18807101
TI  - Rash, strontium ranelate and DRESS syndrome put into perspective. European
      Medicine Agency on the alert.

PMID- 18807102
TI  - Leprosy-related joint involvement.
AB  - We estimate the prevalence and evaluate the clinical characteristics of leprosy
      related arthritis. One thousand, two hundred fifty-seven leprosy patients were
      attended at "Alfredo da Matta" outpatient clinic in the state of Amazonas, Brazil
      from July to October 2004. Among them, 115 patients were identified with
      articular pain and were referred for evaluation with rheumatologist. Blood
      samples were collected and radiological evaluation of the involved joints was
      performed. All patients with arthritis who continued to be followed up were
      reevaluated. One hundred fifteen leprosy patients (9.1%) were identified with
      articular involvement. The articular complaints were attributed to a defined
      rheumatic disease in 36 cases and excluded from further analysis. Twenty-four
      patients had arthralgia, and 55 (37 males and 18 females) had leprosy-related
      arthritis. The prevalence of arthritis was similar in both genders, and all
      patients with leprosy-related arthritis had lepromatous or borderline type. Most
      of patients had polyarticular and symmetrical arthritis and had completed the
      multidrug therapy and was under reaction treatment. The mean duration of
      articular symptoms at the time of study was 1.06 years (ranging from 5 days to 14
      years). Ninety-one percent of patients with leprosy-related arthritis presented
      erythema nodosum leprosum or reversal reactions. Only five patients with
      arthritis had never presented reactions. Fifty percent of patients became
      asymptomatic during the mean 24 months of follow-up. Leprosy-related arthritis
      has a lower prevalence than previously reported. Most cases of leprosy-related
      arthritis were associated with reactional episodes, and in a large number of
      cases, the arthritis had a chronic course not responsive to the conventional
      therapy for reactions.

PMID- 18807103
TI  - Analyses of differential proteome of human synovial fibroblasts obtained from
      arthritis.
AB  - There is mounting evidence indicating that the synovial fibroblasts (SFs)
      contribute to the pathogenesis of rheumatoid arthritis (RA). The present study
      showed the differential proteins expression pattern of SFs from patients with RA
      or osteoarthritis (OA) and healthy control. Cellular proteins of cultured SFs
      were subjected to 2-DE and visualized by silver nitrate staining. A total of 49
      spots that were statistically and differentially overexpressed in RA or OA in
      comparison to healthy ones were identified by MALDI-TOF-MS, and 25 proteins were
      successfully identified. Western blot was used to further verify some of the
      differential proteins. These proteins included enzymatic and structural proteins,
      signal transduction proteins, calcium binding protein, etc. From all of the
      identified proteins, a number of proteins have been implicated that involved in
      the healthy or pathological SFs function (e.g., S100A4, S100A10, cathepsin D) or
      that have potential diagnostic and prognostic value for RA (alpha-enolase and
      TPI) or that may be the new therapeutic targets (Annexin, SOD, PRX).

PMID- 18807104
TI  - Spontaneous rapid resolution of acute subdural hematoma after head trauma: is it
      truly rare? Case report and relevant review of the literature.
AB  - BACKGROUND: Spontaneous rapid resolution of acute subdural hematoma (ASDH) is a
      rare phenomenon for this severe insult after head trauma. CASE REPORT: We present
      a 22-year-old patient who developed ASDH with a moderate midline shift and
      compression of lateral ventricle after a truncal collision but without a direct
      beat on the head. Conservative management was performed under close monitoring
      because of unexpected improvement of clinical signs and symptoms. Unexpectedly,
      the ASDH resolved spontaneously within 13 h after the trauma, and he was
      discharged 1 week later without any neurological deficit. In addition, similar
      cases reported in literature were reviewed. CONCLUSION: Because most of the
      patients developing ASDH underwent emergent surgical intervention, the incidence
      of this phenomenon may be underestimated. Although emergent surgical removal
      remains the first choice for the treatment of ASDH, conservative management with
      careful monitoring may also work out in selected patients who show neurologic and
      radiologic improvements.

PMID- 18807105
TI  - Spirulina enhanced the skeletal muscle protein in growing rats.
AB  - BACKGROUND/AIM OF THE STUDY: This study evaluates the effects of the blue green
      alga spirulina as the sole dietary source of protein on muscle protein in weaning
      rats. METHODS: Young (30 days) Wistar rats were fed, during 60 days, with 17%
      protein spirulina (S) and compared to rats fed 17% protein casein (C). We
      evaluated the muscle total protein and DNA contents and the in vitro protein
      synthesis and degradation rates as well the myosin protein expression. RESULTS:
      The groups presented similar body weight (C = 427.3 +/- 8.6; S = 434.6 +/- 7.7 g)
      and length (C = 25.4 +/- 0.2; S = 25.6 +/- 0.2 cm). Soleus muscle total protein
      (C = 2.9 +/- 0.1; S = 2.7 +/- 0.1 mg/100 mg) and DNA (C = 0.084 +/- 0.005; S =
      0.074 +/- 0.005 mg/100 mg) contents were also similar in both groups. Protein
      degradation (C = 427.5 +/- 40.6; S = 476.7 +/- 50.5 pmol/mg(-1) h(-1)) did not
      differ between the groups but protein synthesis (C = 17.5 +/- 1.0; S = 25.2 +/-
      1.9 pmol/mg(-1) h(-1)) and myosin content (western blot analyses) were higher (P
      < 0.05, t test) in spirulina group. CONCLUSIONS: Although the spirulina proved
      adequate protein quality to maintain body growth, the muscle protein synthesis
      rates were increased by the ingestion of the experimental diet in young rats.

PMID- 18807106
TI  - Oxidative stress-induced insulin resistance in skeletal muscle cells is
      ameliorated by gamma-tocopherol treatment.
AB  - BACKGROUND: Oxidative stress-induced reactive oxygen species are associated with
      the clinical manifestation of insulin resistance. Evidence suggests that
      antioxidant treatment may reduce this incidence. AIM OF THE STUDY: This study
      determined whether glucose oxidase (GO)-induced insulin resistance in cultured
      skeletal muscle cells could be ameliorated by pre-treatment with gamma-tocopherol
      (GT). METHODS: Insulin sensitivity in L6 myotubes was assessed by 2-deoxy-D: 
      [(3)H]-glucose uptake. The phosphorylation of distal insulin signaling proteins
      Akt and the Akt substrate AS160 were determined by western blot. RESULTS: One
      hour treatment with 100 mU/ml GO decreased insulin-stimulated glucose uptake (P <
      0.001). Pre-treatment with GT either partially (100 microM) or completely (200
      microM) restored insulin-stimulated glucose uptake in cells after GO-induced
      insulin resistance. GO-induced oxidative stress did not impair insulin stimulated
      phosphorylation of Akt or AS160, but 200 microM GT increased insulin-stimulated
      phosphorylation of these key signaling proteins (P < 0.05). CONCLUSIONS: High
      dose (200 microM) GT treatment ameliorated oxidative stress-induced insulin
      resistance in cultured rat L6 skeletal muscle cells.

PMID- 18807107
TI  - Differential inflammatory status in rats susceptible or resistant to diet-induced
      obesity: effects of EPA ethyl ester treatment.
AB  - BACKGROUND: Obesity has been associated with a chronic low degree inflammatory
      response, characterized by an increase of inflammatory adipocytokines like
      tumoral necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) as well as the
      synthesis of acute phase reactants such as haptoglobin. AIM OF THE STUDY: To
      evaluate if impairments in the inflammatory response at the white adipose tissue
      (WAT) level could be involved in the mechanisms conferring susceptibility or
      resistance to high-fat diet-induced obesity (DIO). METHODS: The expression levels
      of WAT genes and systemic markers related to inflammation were evaluated in two
      groups of rats fed with a high-fat diet during 15 days that showed either an
      early susceptibility (DIO) or resistance (DR) to develop obesity. We also tested
      the efficacy of the eicosapentaenoic (EPA) omega-3 fatty acid treatment (35 days)
      to potentially counteract the obesity-associated inflammatory features in DIO
      rats. RESULTS: This trial showed that high-fat diet induces an increase on mRNA
      levels on TNF-alpha and haptoglobin in DIO animals (P < 0.05), while no
      significant changes were observed on DR rats. Furthermore, a significant increase
      in IL-6 mRNA (P < 0.05) was found in both DR and DIO rats. EPA-treatment caused a
      significant decrease in IL-6 mRNA (P < 0.05), without significant changes in
      haptoglobin mRNA levels in adipose tissue. An unexpected decrease was observed in
      haptoglobin serum levels (P < 0.05) in DIO rats, which was reverted to control
      values in EPA-treated animals. CONCLUSIONS: Our data suggest that obesity
      susceptibility or resistance may depend on the genetic make up related to
      inflammatory features, and support a role for omega-3 fatty acids in the
      prevention of obesity-associated inflammation in adipose tissue. In addition, our
      data do not support the hypothesis that serum haptoglobin is an acute phase
      protein expected to be positively related to increased adiposity in rats, at
      least in early and medium stages of DIO.

PMID- 18807108
TI  - Six weeks phylloquinone supplementation produces undesirable effects on blood
      lipids with no changes in inflammatory and fibrinolytic markers in postmenopausal
      women.
AB  - BACKGROUND: Cardiovascular disease is the major cause of death in the Western
      world, but some recent studies indicate that vitamin K may play a role in
      atherosclerosis protection. AIM OF STUDY: The aim of this study was to evaluate
      the effect of phylloquinone supplementation on blood lipids, inflammatory markers
      and fibrinolytic activity in postmenopausal women. METHODS: Thirty-one
      postmenopausal women completed this placebo-controlled, randomized crossover
      study and received 500 microg phylloquinone or placebo in addition to their
      habitual diet during two periods of 6 weeks' duration. Blood concentration of
      lipids, inflammatory markers and fibrinolytic parameters were measured after each
      period. RESULTS: Inflammatory markers, fibrinolytic parameters, total cholesterol
      and LDL-C were unaffected by the supplementation, whereas a 15% increase was seen
      in triacylglycerols (P = 0.015) and a 5% decrease in HDL-C (P = 0.06).
      CONCLUSIONS: Six weeks supplementation with a dose of phylloquinone similar to
      that obtainable from the diet induced a deterioration of the lipid profile with
      no improvement in any of the other risk markers analysed. Thus, these results do
      not support a cardioprotective effect of vitamin K as has been suggested by
      others.

PMID- 18807109
TI  - High frequency of co-segregating CLCN1 mutations among myotonic dystrophy type 2
      patients from Finland and Germany.
AB  - Based on previous reports the frequency of co-segregating recessive chloride
      channel (CLCN1) mutations in families with myotonic dystrophy type 2 (DM2) was
      suspected to be increased. We have studied the frequency of CLCN1 mutations in
      two separate patient and control cohorts from Germany and Finland, and for
      comparison in a German myotonic dystrophy type 1 (DM1) patient cohort. The
      frequency of heterozygous recessive chloride channel (CLCN1) mutations is
      disproportionally higher (5 %) in currently diagnosed DM2 patients compared to
      1.6 % in the control population (p = 0.037), while the frequency in DM1 patients
      was the same as in the controls. Because the two genes segregate independently,
      the prevalence of CLCN1 mutations in the total DM2 patient population is, by
      definition, the same as in the control population. Our findings are, however, not
      based on the total DM2 population but on the currently diagnosed DM2 patients and
      indicate a selection bias in molecular diagnostic referrals. DM2 patients with co
      segregating CLCN1 mutation have an increased likelihood to be referred for
      molecular diagnostic testing compared to DM2 patients without co-segregating
      CLCN1 mutation.

PMID- 18807110
TI  - Associations between maternal closeness, suicidal ideation, and risk behaviors in
      Cape Town.
AB  - Health compromising behaviors, such as smoking and other risk behaviors tend to
      co-occur, and contribute to the leading causes of preventable death, disease, and
      disability among adolescents and young adults worldwide. The present study
      assesses a model of the direct and indirect effects of maternal closeness with
      suicidal ideation on smoking and risky behaviors. The sample consisted of 657
      South African youth assessed over two time points with comparison of effects
      between males and females. Maternal closeness had a significant effect on
      suicidal ideation among females. Suicidal ideation had a significant effect on
      risky behaviors among males and lifetime smoking among females. A significant
      indirect effect was observed from maternal closeness to lifetime smoking among
      females. These results indicate that suicidal ideation is associated with
      lifetime smoking and risky behaviors separately among male and female adolescents
      and highlight the need to focus on the development of mental health preventive
      interventions for both genders.

PMID- 18807111
TI  - Psychometric evaluation of social phobia and anxiety inventory for children (SPAI
      C) and social anxiety scale for children-revised (SASC-R).
AB  - The study evaluated the psychometric properties of Finnish versions of the Social
      Phobia and Anxiety Inventory for Children (SPAI-C) and the Social Anxiety Scale
      for Children-Revised (SASC-R). 352 students (M = 12.2 years) participated in the
      study and completed the SPAI-C and SASC-R. In addition, 68 participants (M = 12.2
      years) and their parents were interviewed with the Schedule for Affective
      Disorders and Schizophrenia for School Aged Children (K-SADS-PL). The SPAI-C was
      more sensitive for identifying youth meeting criteria for social phobia (SP),
      whereas the SASC-R demonstrated greater specificity. The youth in this sample had
      lower mean total scores on the self-report questionnaires than did those in the
      original validitation studies of the SPAI-C and SASC-R conducted in America.
      These findings question whether cross-cultural differences in the expression of
      SP influence the clinical cut-off scores used in translated versions of social
      anxiety questionnaires.

PMID- 18807112
TI  - Examining relations between psychopathology and psychopathy dimensions among
      adolescent female and male offenders.
AB  - AIM: This study was performed to investigate relations between psychopathology
      and psychopathy in adolescent female and male detainees. METHOD: We examined 91
      male and 123 female adolescent detainees (aged 14-19) for psychopathology -using
      the Youth Self Report, the Overt Aggression Scale-Modified and a Conduct Disorder
      Self Report Scale- and for psychopathic dimensions using the psychopathy
      checklist youth version (PCL:YV). Based on a linear regression analysis we
      compared the specific associations between psychopathology and psychopathy in
      both male and female delinquent juveniles. RESULTS: Our results revealed higher
      scores for externalizing behavior and psychopathic dimensions in delinquent
      males, and higher internalizing problem scores in delinquent females.
      Furthermore, we found a positive relationship between suicidal behavior and the
      psychopathy total score as well as the affective, the lifestyle and the
      antisocial dimension only in girls. No association was found for suicidal
      behavior in boys. Regarding anxious-depressive behavior, we found a negative
      relation to the psychopathy total score and to the affective psychopathy factor
      for the boys. CONCLUSION: Expectedly, the population of incarcerated adolescents
      exhibited a high prevalence of psychopathology. At the same time our results
      referred to meaningful gender-related differences with respect to associations
      with psychopathy. The gender-related differences in psychopathological symptoms
      could indicate varied subtypes of psychopathy in boys and girls.

PMID- 18807113
TI  - Isolation, characterization and genome sequencing of phage MZTP02 from Bacillus
      thuringiensis MZ1.
AB  - A lysogenic phage, MZTP02, was produced via induction by mitomycin C from
      Bacillus thuringiensis (B. thuringiensis) strain MZ1. Plaques were about 3 mm in
      diameter with a small inner zone consisting of new B. thuringiensis colonies.
      Electron microscopic analysis showed that MZTP02 had a long tail (220 nm x 18 nm)
      and an icosahedral head (82 nm x 85 nm). MZTP02 was insensitive to organic
      solvents such as chloroform, and infected six B. thuringiensis strains. Its
      complete genome contained 15,717 base pairs (bp) with 37.55% G + C content. Two
      inverted terminal repeats consisting of 40 bp were 65% identical. Twenty putative
      open reading frames (ORFs) were found in the MZTP02 genome, and nine predicted
      proteins, including two terminase subunits, portal protein, minor head protein,
      scaffold protein, two putative membrane proteins, tail component, and minor
      structural protein, showed similarity to other phage proteins. But six ORFs were
      unique. The presence of a terminal protein at the 5'-terminus was demonstrated
      using proteinase K, lambda exonuclease and E. coli exonuclease III to digest the
      genome DNA. A TMP phylogenetic tree was constructed based on amino acid sequences
      from ten phages.

PMID- 18807114
TI  - Stability of varicella-zoster virus open reading frame 63.
AB  - The stability of varicella-zoster virus (VZV) open reading frame (ORF) 63 was
      analyzed by sequential passage of a virus strain in cell culture. VZV was
      propagated in culture for 1,206 passages. ORF63 from six passages (18, 220, 516,
      730, 1060, and 1,206) was selected and sequenced. Among the six passages, only
      passage 1,206 showed point mutations at three locations: 551, 618 and 661. In
      addition, western blot analysis with anti-ORF63 monoclonal antibodies showed no
      discernable difference in the size of the ORF63 gene product from passage 18 and
      that from passage 1,206. These results indicate the stability of VZV ORF63 gene
      in culture over 1,206 passages.

PMID- 18807115
TI  - New BZLF1 sequence variations in EBV-associated undifferentiated nasopharyngeal
      carcinoma in southern China.
AB  - The viral lytic gene BZLF1 triggers replication of the Epstein-Barr virus (EBV),
      which is commonly found in nasopharyngeal carcinoma (NPC). Here, RT-PCR revealed
      five new BZLF1 variants in 8 of 12 NPC and 4 of 12 non-NPC nasopharyngeal
      biopsies from an NPC-endemic area in southern China. The deduced peptide sequence
      of the dominant BZLF1 variant differed by 11 amino acids from that of the
      prototypical strain B95.8 (V01555). Anti-ZEBRA antibody levels were higher in NPC
      than that in non-NPC patients (P < 0.001). These findings demonstrated a dominant
      BZLF1 variant in southern Chinese EBV-associated NPC and non-NPC patients.

PMID- 18807116
TI  - Characterisation of lettuce virus X, a new potexvirus infecting lettuce in Iran.
AB  - A virus with flexuous rod-shaped particle morphology was found in samples from
      lettuce during a survey of viruses infecting lettuce in Tehran province in Iran.
      This virus was subjected to a complete analysis of its biological and molecular
      features. The entire nucleotide sequence of the virus was determined, revealing a
      polyadenylated ssRNA genome consisting of 7,212 nucleotides [without poly (A)
      tail] and possessing an organization typical for potexviruses. Comparative genome
      analysis showed that the lettuce virus is closely related to Alstroemeria virus
      X, narcissus mosaic virus and asparagus virus 3. Based on particle morphology,
      physico-chemical properties and the complete genome sequence, this virus is a
      member of a new species in the genus Potexvirus, for which the name lettuce virus
      X (LeVX) is proposed. Biological assays using an infectious cDNA clone and a wild
      type isolate of LeVX revealed that the virus, despite reaching high
      concentrations in all lettuce cultivars tested, does not cause symptoms in
      lettuce.

PMID- 18807118
TI  - Embryology of Ceratopteris richardii (Pteridaceae, tribe Ceratopterideae), with
      emphasis on placental development.
AB  - This comprehensive study of early embryology in Ceratopteris richardii combines
      light microscopy with the first ultrastructural evaluation of any pteridophyte
      embryo. Emphasis is placed on ontogeny of the foot and placental transfer cells.
      The embryology of C. richardii shares many similarities with that of other
      polypodiacious ferns while exhibiting distinctive division patterns. Formative
      embryonic stages have been reconstructed into three-dimensional models for ease
      of interpretation. The zygote divides perpendicular to the gametophyte plane and
      anterioposterior axis. This division establishes a prone embryological habit that
      maximizes rapid independent establishment of a leaf-root axis in a cordate
      gametophyte. After the formation of a globular eight-celled stage, initials of
      the first leaf, and root and shoot apical meristems are defined early by discrete
      formative divisions. Concomitantly, the foot expands and differentiates to
      transport nutrients from the gametophyte for the developing embryonic organs.
      Transfer cell wall ingrowth deposition begins in the gametophyte placental cells
      before the adjacent sporophyte cells just after the eight-celled stage. These
      observations provide an anatomical framework for future comparative developmental
      genetic studies of embryogenesis in free-sporing plants.

PMID- 18807117
TI  - Cell-specific association of heat shock-induced proton flux with actin ring
      formation in Chenopodium cells: comparison of auto- and heterotroph cultures.
AB  - A comparison of the responses of extracellular pH, buffering capacity and actin
      cytoskeleton in autotroph and heterotroph Chenopodium rubrum cells to heat shock
      revealed cell-specific reactions: alkalinization caused by the heat shock at 25
      35 degrees C was higher in heterotroph cells and characterized by heat shock
      induced changes in the actin cytoskeleton and ring formation at 35-37 degrees C.
      Rings (diameter up to 3 mum) disappeared and extracellular pH recovered after the
      heat-shocked cells were transferred into control medium. At 41 degrees C, no
      rings but a network of coarse actin filaments were induced; at higher
      temperatures, fragmentation of the actin cytoskeleton and release of buffering
      compounds occurred, indicating sudden membrane leakage at 45-47 degrees C. The
      calcium chelator EGTA [ethylene-glycol-bis(beta-aminoethyl-ether)-N,N,N',N'
      tetraacetic-acid] increased the frequency of heat shock-induced rings. Ionophore
      (10 microM nigericin) and the sodium/proton antiport blocker [100 microM 5-(N
      ethyl-N-isopropyl)-amiloride] mimicked the effect of the 37 degrees C heat shock.
      The cytoskeleton inhibitors latrunculin B, cytochalasin D and 2,3-butanedione
      monoxime inhibited ring formation but not alkalinization. In autotroph cells, the
      treatment with nigericin (10 microM) produced rings, although the actin
      cytoskeleton was not affected by temperatures up to 45 degrees C. We conclude
      that Chenopodium cells express a specific temperature sensor that has ascendancy
      over the organization of the actin cytoskeleton; this is probably a temperature-
      and potential-sensitive proton-transporting mechanism that is dependent on the
      culture conditions of the heterotroph cells.

PMID- 18807119
TI  - Photosynthetic performance along a light gradient as related to leaf
      characteristics of a naturally occurring Cypripedium flavum.
AB  - Photosynthesis, leaf structure, nitrogen content and nitrogen allocation in
      photosynthetic functions of Cypripedium flavum were studied in a naturally
      varying light regime. Light-saturated leaf net photosynthetic rate (A max) was
      strongly correlated with leaf dry mass per area (LMA), mesophyll conductance (g
      (m)) and area-based leaf nitrogen content (N area), with all variables increasing
      with increasing irradiance. Such coordinate variation of all these parameters
      illustrates the plastic response of leaf structure to high light (HL). Leaf N
      area was greater under HL than in low light (LL). The fractions of leaf nitrogen
      partitioning in carboxylation (P (R)) and bioenergetics (P (B)) were positively
      related to LMA. In contrast, P (R) and P (B) decreased with increasing mass-based
      leaf nitrogen content (N mass). However, no correlation was found between leaf
      nitrogen investment in light harvesting (P (L)) and either LMA or N mass. Like
      maximum rate of carboxylation (V cmax) and electron transport (J max), the J
      max/V cmax ratio, which was strongly correlated to LMA, also increased
      significantly with irradiance. Under HL, leaf maximum photosynthetic nitrogen
      efficiency (ANUE) and intrinsic water use efficiency (WUE) were greater than in
      LL conditions, despite a small difference in WUE. This suggests that a functional
      balance in the photosynthetic machinery favors leaf photosynthetic plasticity of
      C. flavum in response to different light conditions. Given an ample soil nitrogen
      supply, C. flavum may offset its susceptibility to HL by efficient nitrogen use
      and higher stomatal and mesophyll conductance against photoinhibition so as to
      keep leaf photosynthesis positive.

PMID- 18807120
TI  - Pure red cell aplasia associated with hemolytic anemia refractory to standard
      measures and resolved by rituximab in an elderly patient.

PMID- 18807121
TI  - Use of urine cytology in the diagnosis of genitourinary relapse of acute
      promyelocytic leukemia after allogenic stem cell transplant.

PMID- 18807122
TI  - MR-guided vacuum-assisted breast biopsy: is it an essential technique?
AB  - BACKGROUND: In the United States and Europe, MR-guided vacuum-assisted biopsy
      (VAB) is required for MR-only visible suspicious lesions that cannot be
      identified with mammography or ultrasonography. However, it is controversial as
      to whether MR-guided VAB is essential or not in Japan. The purpose of this study
      was to clarify the frequency of malignancy among the patients that underwent MR
      guided VAB, and to discuss the need for this technique in Japan. METHODS: This
      study was approved by the Institutional Review Board of our hospital. A
      retrospective review was performed of 30 consecutive patients who had undergone
      MR-guided 11-gauge VAB. The biopsies were performed on a 1.5 T MR scanner using a
      commercially available biopsy system. All lesions seen with MRI could not be
      detected by mammography and second-look ultrasonography. RESULTS: All 30 lesions
      were assessed as category 4 or 5. The average lesion size of a mass enhancement
      before biopsy was 0.7 cm, and the average lesion size of a non-mass-like
      enhancement was 2.3 cm. The average number of cores of VAB was 19. The median
      time required to perform the VAB procedure was 35 min. The biopsy was
      successfully performed without important side effects in all patients.
      Histopathological findings were invasive ductal carcinoma in one (3%); ductal
      carcinoma in situ (DCIS) in seven (23%); and benign in 22 (73%). In one case,
      atypical ductal hyperplasia at VAB was upgraded to DCIS at surgical excision.
      CONCLUSION: MR-guided VAB can be performed safely and it is needed for MR-only
      visible suspicious lesions in Japan.

PMID- 18807123
TI  - Efficacy of S-1 in heavily pretreated patients with metastatic breast cancer:
      cross-resistance to capecitabine.
AB  - BACKGROUND: It is not clear what the optimal treatment of chemotherapy is for
      patients with heavily treated metastatic breast cancer (MBC). We have
      retrospectively examined the efficacy and safety of S-1 in patients with MBC who
      had been previously treated with anthracycline, taxane, and capecitabine.
      METHODS: Patients with MBC who had been administered S-1, an oral modulated
      compound containing a fluoropyrimidine derivative, between November 2001 and June
      2003 at the Cancer Institute Hospital were retrospectively reviewed. S-1 at a
      standard dose of 50 mg/body was administered twice daily for four weeks, followed
      by a two-week rest period. This was repeated every six weeks until disease
      progression or unacceptable toxicity. RESULTS: Thirty-five patients were
      assessed. The patients were heavily pretreated with anthracycline (100%), taxane
      (paclitaxel or docetaxel) (100%), capecitabine (100%), vinorelbine (71%), and
      mitomycin (69%). Median follow-up time of patients was 9.6 months (range, 1.2
      26.6). ORR was 3% (95% confidence interval: 0-9%), and CBR was 20% (95%
      confidence interval: 6-33%). Time to treatment failure was 2.8 months. Overall
      survival was 21.4 months. Grade 1 or 2 adverse events were observed in 17% and
      13%, respectively. Grade 3 events occurred as anorexia (9%), nausea (9%),
      vomiting (9%), diarrhea (14%), fatigue (3%), and elevation of AST/ALT (3%). No
      grade 3 was seen as hand-foot syndrome. Neither grade 3 nor 4 was observed in
      bone marrow suppression. CONCLUSIONS: S-1 was fairly well tolerated, but
      demonstrated very limited activity in capecitabine-pretreated patients who had
      already been exposed to anthracycline and taxane. It was suggested that S-1
      clinically exhibited cross-resistance to capecitabine.

PMID- 18807124
TI  - Preliminary result of accelerated partial breast irradiation after breast
      conserving surgery.
AB  - PURPOSE: To investigate the feasibility of accelerated partial breast irradiation
      (APBI) for Japanese patients, we started high-dose-rate interstitial
      brachytherapy (HDR-ISBT) as monotherapy after breast-conserving surgery (BCS).
      METHODS: We implanted 45 Tis-2 breast cancer patients at National Hospital
      Organization Osaka National Hospital between June 2002 and June 2006. Our
      eligibility criteria were broader than the ones used previously in western
      countries. We included margin-positive cases and younger patients (median age:
      44; range: 26-68) to adapt the criteria for Japanese women. Total prescribed
      doses were 36-42 Gy in six to seven fractions, and the volumes encompassed by
      100% prescribed dose (V100) were 38.5-315.1 cc. Fifteen patients received
      chemotherapy. RESULTS: Treatment could be completed for all patients. Two local
      failures (4%) and two distant metastases were observed, while one patient died of
      liver metastasis. Seven wound complications, four with and three without
      infection, and two rib fractures occurred. The significant risk factors for wound
      complications were non-administration of prophylactic antibiotics during ISBT (P
      < 0.01), open cavity implant (P < 0.05), large V100 (P < 0.01), V150 (P < 0.05),
      and V200 (P < 0.05). CONCLUSION: APBI after BCS for Japanese women with
      relatively small breasts was well tolerated, but special care should be taken
      with treatment technique.

PMID- 18807125
TI  - Colorectal endoscopic submucosal dissection: present status and future
      perspective, including its differentiation from endoscopic mucosal resection.
AB  - Endoscopic submucosal dissection (ESD) allows en bloc resection of a lesion,
      irrespective of the size of the lesion. ESD has been established as a standard
      method for the endoscopic ablation of malignant tumors in the upper
      gastrointestinal (GI) tract in Japan. Although the use of ESD for colorectal
      lesions has been studied via clinical research, ESD is not yet established as a
      standard therapeutic method for colorectal lesions because colorectal carcinoma
      has unique pathological, organ specific characteristics that differ radically
      from those of the esophagus and stomach, and scope handling and control is more
      difficult in the colorectum than in the upper GI tract. Depending on the efficacy
      of endoscopic mucosal resection (EMR) and the clinicopathological characteristics
      of the colorectal tumor, the proposed indications for colorectal ESD are as
      follows: (1) lesions difficult to remove en bloc with a snare EMR, such as
      nongranular laterally spreading tumors (particularly the pseudo depressed type),
      lesions showing a type VI: pit pattern, and large lesions of the protruded type
      suspected to be carcinoma; (2) lesions with fibrosis due to biopsy or peristasis;
      (3) sporadic localized lesions in chronic inflammation such as ulcerative
      colitis; and (4) local residual carcinoma after EMR. Colorectal ESD is currently
      in the development stage, and a standard protocol will be available in the near
      future. We hope that colorectal tumors will be efficiently treated by a treatment
      method appropriately selected from among EMR, ESD, and surgical resection after
      precise preoperative diagnosis based on techniques such as magnifying
      colonoscopy.

PMID- 18807126
TI  - Role of orexin in central regulation of gastrointestinal functions.
AB  - Orexins are neuropeptides that are localized in neurons within the lateral
      hypothalamus and regulate feeding behavior. The lateral hypothalamus plays an
      important role in not only feeding but also in the central regulation of gut
      function. Along this line, accumulating evidence has shown that orexins act in
      the central nervous system to regulate gastrointestinal functions. The purpose of
      this review is to summarize recent relevant findings on brain orexins and the
      digestive system, and discuss the pathophysiological roles of these peptides.
      Centrally administered orexin or endogenously released orexin in the brain
      potently stimulates gastric acid secretion in rats. The vagal cholinergic pathway
      is involved in the orexin-induced stimulation of acid secretion. Because of its
      stimulatory action on feeding, it can be hypothesized that orexin in the brain is
      a candidate mediator of cephalic phase gastric secretion. In addition, brain
      orexin may be involved in the development of depression and functional
      gastrointestinal disorders, which are frequently accompanied by inhibition of gut
      function, because lack of orexin activity might cause the inhibition of gastric
      physiological processes and evoke a depressive state. These lines of evidence
      suggest that orexin in the brain is a potential molecular target for treatment of
      functional gastrointestinal disorders.

PMID- 18807127
TI  - Relationship between the in vitro response of dendritic cells to Lactobacillus
      and prevention of tumorigenesis in the mouse.
AB  - BACKGROUND: Some strains of lactobacilli stimulate immune cells, yet little is
      known about their potency in cancer prevention. We have previously reported that
      Lactobacillus casei Shirota (LcS) suppresses murine tumorigenesis through immune
      modulation. In this study, differences were compared among six representative
      strains of lactobacilli in regard to their ability to stimulate bone marrow cell
      derived dendritic cells (BMDCs) in vitro and tumor suppression in vivo. METHODS:
      BM-DCs were cocultured with a Lactobacillus strain in vitro, and the interleukin
      (IL)-12 released into the culture supernatant was measured by enzyme-linked
      immunosorbent assay. Tumors were chemically induced by a single subcutaneous
      injection of 3-methylcholanthrene (MC) in BALB/c mice. The test diets containing
      Lactobacillus were given from the day of the MC injection, and the tumor
      incidences were monitored. Peyer's patches were dissected from Lactobacillus-fed
      mice, and the status of c-Src, a regulator of DCs, in Peyer's patch cells was
      examined by Western blotting. RESULTS: In the coculture system, L. fermentum FERM
      P-13857 and LcS potently elicited IL-12 production. LcS but not the other strains
      of lactobacilli showed tumor suppression. The inactive form of c-Src,
      phosphorylated at Tyr527, was dominantly detected in Peyer's patches resected
      from L. fermentum FERM P-13857-fed mice compared with LcS-fed mice. CONCLUSIONS:
      The responses of DCs may be associated with tumor suppression by an ingested
      Lactobacillus strain.

PMID- 18807128
TI  - Efficacy and safety of omeprazole in Japanese patients with nonerosive reflux
      disease.
AB  - BACKGROUND: There is increasing awareness of nonerosive reflux disease (NERD) as
      a disease requiring treatment in Japan. This randomized, double-blind, placebo
      controlled, parallel-group study was conducted to investigate the efficacy and
      safety of omeprazole 10 mg and 20 mg once daily in Japanese patients with NERD.
      METHODS: Patients with heartburn for at least 2 days a week during the month
      before entry into the study and no endoscopic signs of a mucosal break (grade M
      or N according to Hoshihara's modification of the Los Angeles classification)
      were randomly assigned to one of three groups (omeprazole 10 mg or 20 mg, or
      placebo) once daily for 4 weeks. RESULTS: Overall, 355 patients were enrolled, of
      whom 284 were randomly assigned to one of the three groups (omeprazole 10 mg, n =
      96; omeprazole 20 mg, n = 93; placebo, n = 95). The rate of complete resolution
      of heartburn in week 4 was significantly higher in patients treated with
      omeprazole 10 mg [32.3%, 95% confidence interval (CI), 22.9%-41.6%] or 20 mg
      (25.8%, 95% CI, 16.9%-34.7%) than in the placebo group (12.0%, 95% CI, 5.3%
      18.6%). No significant difference between the two omeprazole groups was observed.
      The rate of complete resolution of heartburn by omeprazole was similar between
      patients with grade M and those with grade N esophagus. Omeprazole also increased
      the rate of sufficient relief from heartburn. Omeprazole was well tolerated.
      CONCLUSIONS: Omeprazole 10 mg or 20 mg once daily is effective and well tolerated
      in patients with NERD regardless of their endoscopic classification.

PMID- 18807129
TI  - Management and outcome of peptic ulcers or erosions in patients receiving a
      combination of aspirin plus clopidogrel.
AB  - BACKGROUND: This multicenter retrospective study investigated the management and
      outcome of patients with peptic ulcer/erosion-related aspirin and clopidogrel (A
      + C) cotherapy. METHODS: From January 2002 to September 2006, patients with
      endoscopically proven peptic ulcers/erosions after receiving A + C cotherapy were
      analyzed. RESULTS: This group consisted of 106 patients (age, 69.3 +/- 11.7
      years). Ulcers/erosions developed in 27 patients during hospitalization for
      cardiac events and in 79 patients after hospital discharge. Of 27 patients
      hospitalized for acute cardiac events, gastrointestinal (GI) bleeding and
      dyspepsia occurred in 24 and three, respectively. The most common lesion was
      gastric ulcer. Of 79 discharged patients, GI bleeding and dyspepsia occurred in
      64 and 15, respectively. The most common bleeding and dyspeptic lesions were
      gastric ulcer and gastritis, respectively. Overall, 17 patients underwent
      endoscopic hemostasis all successfully. A + C cotherapy was continued in 57
      patients for a median (interquartile range) of 3.0 (6.2) months. Most were
      coprescribed a proton pump inhibitor (PPI) (53, 93%). No recurrent GI bleeding
      was observed. CONCLUSIONS: After A + C cotherapy, gastric ulcer or gastritis were
      the most common endoscopic lesions. The combination of a PPI and endoscopic
      treatment for ulcer bleeding was highly successful. After patient stabilization,
      continuation of A + C cotherapy with a PPI appears to be safe.

PMID- 18807130
TI  - The role of nuclear factor-kappaB in the effect of angiotensin II in the
      paraventricular nucleus in protecting the gastric mucosa from ischemia
      reperfusion injury in rats.
AB  - BACKGROUND: The purpose of this study was to elucidate the role of nuclear factor
      kappaB (NF-kappaB) in the development of gastric ischemia-reperfusion (GI-R)
      injury and in mediating the effects of angiotensin II (Ang II) in the
      paraventricular nucleus (PVN) on GI-R injury. METHODS: GI-R injury was induced in
      rats by clamping the celiac artery for 30 min and then reperfusing for 1 h. A
      cannula was inserted into the unilateral PVN for microinjection of Ang II. The
      expressions and levels of NF-kappaB (p65), IkappaB-alpha, and phosphorylated
      IkappaB-alpha in rat gastric mucosa were examined by Western blotting and
      immunohistochemistry. A laser Doppler flowmeter was used to assess gastric blood
      flow (GBF). Malondialdehyde (MDA) was determined using the thiobarbituric acid
      (TBA) method, and superoxide dismutase (SOD) activity was determined by the
      xanthine/xanthine oxidase method. RESULTS: Microinjection of Ang II (3, 30, and
      300 ng) into the PVN dose-dependently inhibited GI-R injury. The levels and
      expressions of NF-kappaB (p65) and phosphospecific IkappaB-alpha protein
      increased 1 h after GI-R and were markedly reduced by microinjection of Ang II
      into the PVN. In contrast, the level and expression of IkappaB-alpha protein
      decreased 1 h after ischemia-reperfusion and recovered to the normal level by
      microinjection of Ang II into the PVN. The effects of Ang II were prevented by
      pretreatment with the Ang II AT1 receptor antagonist losartan (5 microg)
      microinjected into the lateral cerebral ventricle. Inhibition of NF-kappaB
      activity by pyrrolidine dithiocarbamate (PDTC, 200 mg/kg) produced similar
      effects in rats subjected to ischemia-reperfusion with or without microinjection
      of Ang II into the PVN. Administration of PDTC attenuated gastric mucosal injury
      and suppressed the activation of NF-kappaB (p65). Ang II microinjection into the
      PVN increased GBF and decreased the MDA content but did not alter SOD activity in
      the gastric mucosa following ischemia-reperfusion. CONCLUSIONS: NF-kappaB plays a
      role in PVN Ang II-mediated protection against GI-R injury. These central effects
      of Ang II are mediated by AT1 receptors.

PMID- 18807131
TI  - Perfectionism underlying psychological background correlated with the symptoms of
      functional dyspepsia.
AB  - BACKGROUND: Early satiety, bloating, and postprandial distress are common
      symptoms in patients with functional dyspepsia (FD) and anorexia nervosa (AN).
      Perfectionism is known to be associated with AN, accompanied by abnormal eating
      behavior. We analyzed perfectionism in FD as compared with that in AN, and
      investigated the correlation of perfectionism with abdominal symptoms. METHODS:
      The study group comprised 168 patients with FD according to the Rome II criteria
      (65% females, mean age 47.7 years) and 101 with AN according to the DSM-IV
      criteria (100% females, mean age 23 years). As control, 130 healthy subjects (81%
      females, mean age 26.2 years) were studied. Frost's Multidimensional
      Perfectionism Scale (FMPS) was used to evaluate perfectionism. Abdominal symptoms
      were evaluated on the Gastrointestinal Symptoms Rating Scale (GSRS). RESULTS: All
      subscale scores except for organization were significantly higher in patients
      with AN than in controls. The parental criticism (PC) score in patients with FD
      was also significantly higher than that in controls, but lower than that in
      patients with AN. PC was significantly correlated with the total GSRS,
      particularly indigestion scores of FD patients (P = 0.0476 and P = 0.0294).
      CONCLUSIONS: Perfectionism such as PC underlying the psychological background of
      FD patients may be correlated with their abdominal symptoms.

PMID- 18807132
TI  - Role of host interleukin 1beta gene (IL-1B) and interleukin 1 receptor antagonist
      gene (IL-1RN) polymorphisms in clinical outcomes in Helicobacter pylori-positive
      Turkish patients with dyspepsia.
AB  - BACKGROUND: Helicobacter pylori infection leads to different clinical outcomes
      depending on both host and bacterial factors. In a recent study, we identified H.
      pylori cagE and babA2 genotypes as independent predictors of duodenal ulcer (DU)
      and gastric cancer (GC) in dyspepsia patients, but no previous studies have
      examined the role of host-related genetic factors in Turkey. This time our aim
      was to evaluate whether polymorphisms of the interleukin 1B (IL-1B) and the
      interleukin 1 receptor antagonist (IL-1RN) genes are important factors in the
      differential expression of gastroduodenal diseases in H. pylori-positive
      dyspepsia patients. METHODS: Ninety-three H. pylori-positive patients, 30 with
      nonulcer dyspepsia (NUD), 30 with DU, and 33 with GC, were investigated. The IL
      1B-511 and IL-1B-31 biallelic polymorphisms, and the IL-1RN intron 2 variable
      number tandem repeat were genotyped by polymerase chain reaction and single
      strand confirmation polymorphism analysis. RESULTS: The IL-1RN-1/1 genotype was
      significantly more prevalent among patients with NUD than among those with GC
      (chi(2) = 9.270; P = 0.002), and the IL-1RN-1/2 genotype was significantly more
      common in patients with GC (chi(2) = 6.01; P = 0.014). Multivariate regression
      analysis showed that cagE, babA2, and IL-1RN-1/2 genotypes were independent
      predictors of GC, but when patients with benign disorders were grouped together
      (NUD + DU) and compared with patients with GC, regression analysis disclosed that
      babA2 (P = 0.000) and IL-1B-31 gene polymorphisms (CC or CT) (P = 0.01) were the
      only independent markers of GC. CONCLUSIONS: When analyzed together with host
      genetic factors, the well established bacterial risk factor babA2 seems to be the
      most important predictor of malignant disorders, and the presence of the IL-1B
      31TT genotype emerges as a protective factor against them.

PMID- 18807133
TI  - Efficacy of combination therapy of antiviral and immunosuppressive drugs for the
      treatment of severe acute exacerbation of chronic hepatitis B.
AB  - BACKGROUND: Patients with severe exacerbation of chronic hepatitis B, sometimes
      developing into fulminant liver failure, are at high risk for mortality even with
      antiviral therapy. The efficacy of immunosuppressive therapy in clinically severe
      exacerbation of chronic hepatitis B has not been well demonstrated. In this
      study, we evaluated the efficacy of the early introduction of immunosuppressive
      therapy in combination with antiviral therapy in such patients. METHODS: Forty
      two patients, 29 men and 13 women, were defined as having severe exacerbation of
      chronic hepatitis B based on our uniform criteria, and were enrolled in this
      study. Sixteen patients between 1982 and 1996 were analyzed retrospectively. We
      defined the criteria of severe disease in 1997, and then began to introduce
      sufficient doses of corticosteroids prospectively. Nucleoside analogs were
      administered in combination with corticosteroids after 1999. Twenty-six patients
      between 1997 and 2007 were analyzed prospectively. RESULTS: In the retrospective
      study between 1982 and 1996, four of 16 (25%) patients recovered. In the
      prospective study between 1997 and 2007, 17 of 26 (65%) patients recovered; 15 of
      17 patients treated with corticosteroids with or without antiviral drugs within
      10 days after the diagnosis of severe disease recovered, none of five treated
      similarly but later than 10 days after the diagnosis recovered, and two of three
      treated with antiviral drugs recovered. CONCLUSIONS: The early introduction of
      sufficient doses of corticosteroids and nucleoside analogs could be one option
      for reversing the potential deterioration of patients with clinically severe,
      life-threatening exacerbation of chronic hepatitis B.

PMID- 18807134
TI  - Transient elastography for measurement of liver stiffness measurement can detect
      early significant hepatic fibrosis in Japanese patients with viral and nonviral
      liver diseases.
AB  - BACKGROUND: Many studies have reported the efficiency of transient elastography,
      a noninvasive, reproducible, and reliable method for predicting liver fibrosis,
      in patients with chronic hepatitis C (CHC) and B (CHB), but there are few reports
      about nonviral chronic liver disease (CLD) such as primary biliary cirrhosis
      (PBC), nonalcoholic steatohepatitis (NAFLD), and autoimmune hepatitis (AIH). We
      therefore compared the efficiency of transient elastography between CHC and
      nonviral CLD. METHODS: We assessed the accuracy of liver stiffness measurement
      (LSM) using Fibroscan, and compared these values with those of hyaluronic acid,
      type 4 collagen, platelet count, prothrombin index, and AST/platelet ratio index
      (APRI) as indices for the diagnosis of liver fibrosis in 114 patients with a
      variety of chronic liver diseases: CHC (n = 51), CHB (n = 11), NAFLD (n = 17),
      PBC (n = 20), and AIH (n = 15). The histology was assessed according to the
      METAVIR score by two pathologists. RESULTS: The number of fibrosis stage
      (F0/1/2/3/4) with CHC was 9/15/12/6/10, and that with nonviral CLD was
      10/21/11/4/6, respectively. The ability, assessed by area under receiver
      operating characteristic (AUROC) curve, to predict liver fibrosis F >or= 2 for
      LSM, HA, type 4 collagen, platelet count, prothrombin index, and APRI, was 0.92,
      0.81, 0.87, 0.85, 0.85, and 0.92 in CHC patients, respectively; and 0.88, 0.72,
      0.81, 0.67, 0.81, and 0.77 in nonviral CLD patients, respectively. CONCLUSIONS:
      In patients with nonviral CLD, LSM was most helpful in predicting significant
      fibrosis (F >or= 2). Transient elastography is a reliable method for predicting
      significant liver fibrosis, not only in CHC patients but also in nonviral CLD
      patients.

PMID- 18807135
TI  - Clinical features of primary sclerosing cholangitis with onset age above 50
      years.
AB  - BACKGROUND: Although there are two peaks in the age distribution of primary
      sclerosing cholangitis (PSC) in Japan, the clinical differences between the
      patients with an older or younger onset age have not been reported. METHODS: We
      compared clinical features of 18 patients with onset age less than 50 years
      (younger group) and ten PSC patients with onset age above 50 years (older group).
      RESULTS: An association with ulcerative colitis (UC) was recognized in six
      patients in the younger group and in one in the older group. High serum IgE (>170
      IU/ml) was observed more frequently in the older than in the younger group (1/10
      vs. 7/8, P = 0.0029). Mean serum IgM tended to be higher in the younger group
      (198 vs. 119 mg/dl, P = 0.083). More patients received liver transplantation or
      continuous bile drainage, or developed liver failure or cholangiocellular
      carcinoma in the younger than in the older group (11/18 vs. 1/10, P = 0.016).
      CONCLUSIONS: Older PSC patients have higher IgE, possibly less association with
      UC, lower IgM, and a better prognosis. The pathogenesis of PSC may be different
      between older and younger patients.

PMID- 18807136
TI  - Cytological characteristics of invasive lobular carcinoma of the human breast.
AB  - In contrast to invasive ductal carcinoma, invasive lobular carcinoma (ILC) of the
      breast is characterized by multiple ipsilateral occurrences and a higher
      incidence in the contralateral breast. It is therefore necessary to examine
      thoroughly whether there is any other carcinoma present before any breast
      conserving surgery is carried out. We cytologically, histologically, and
      ultrastructurally investigated ILC and pure scirrhous carcinoma (PSC), a subtype
      of invasive ductal carcinoma, to establish cytological diagnostic criteria for
      the differential diagnosis of these two types of carcinoma that have high
      histological similarity. Cytologically, ILC cells showed linear or isolated cell
      arrangements and had small nuclei with round homogeneously distributed fine
      granular chromatin. The cytoplasm was light, and individual cells lacked
      cohesion. The carcinoma showed a rosary-like configuration. PSC cells, however,
      showed linear or cordlike arrangements. Individual cells showed a vertical
      arrangement. PSC cells had a linear cytoplasmic edge and were characterized by
      nuclear molding with coarse granular chromatin. These cytological findings were
      supported by histological and ultrastructural findings. These findings may
      contribute to histological estimation of ILC in preoperative cytological
      diagnosis.

PMID- 18807137
TI  - Reduction of retinaldehyde dehydrogenase 1 expression and production in estrogen
      induced prolactinoma of rat.
AB  - Retinoic acid (RA) plays a critical role in normal development and tissue
      maintenance and is also a regulatory factor of anterior pituitary cells. We
      previously demonstrated that a retinoic acid-synthesizing enzyme, retinaldehyde
      dehydrogenase 1 (RALDH1), is expressed in prolactin cells of adult rats and that
      estrogen suppressed RALDH1 expression. It is suggested that RA plays a role as a
      paracrine and/or autocrine signaling molecule in the anterior pituitary gland.
      However, the presence of RALDH1 in pituitary tumors has not been demonstrated. In
      this study, we examined the expression of RALDH1 in diethylstilbestrol-induced
      prolactinoma of LEXF RI rats. Quantitative analysis of mRNA levels by real-time
      PCR demonstrated drastic reduction of RALDH1 expression in the prolactinoma. We
      have also detected both mRNA expression and production by in situ hybridization
      and immunohistochemistry. Both mRNA-expressing cells and immunopositive cells
      remarkably decreased after 4 weeks of treatment with diethylstilbestrol.
      Fluorescence double immunohistochemistry of RALDH1 and prolactin revealed that
      prolactin-immunopositive cells do not colocalize with RALDH1 in the prolactinoma.
      These results suggest that the reduction of local RA generation relates to cell
      proliferation and tumorigenesis of lactotrophs.

PMID- 18807138
TI  - Raloxifene, a selective estrogen receptor modulator, induces mitochondria
      mediated apoptosis in human endometrial carcinoma cells.
AB  - Raloxifene is a nonsteroidal benzothiophene that has also been classified as a
      selective estrogen receptor modulator (SERM) on the basis of studies in which it
      produced both estrogen-agonistic effects on bone and lipid metabolism and
      estrogen-antagonistic effects on uterine endometrium and breast tissue. We
      investigated apoptotic cell death and the apoptotic pathway in human endometrial
      carcinoma cells (Ishikawa cells) expressing estrogen receptor treated with
      raloxifene. Cell viability was significantly decreased in Ishikawa cells treated
      with raloxifene at 20 microM and higher levels. Raloxifene at 20 microM induced
      54% inhibition of cell viability after 48 h treatment. Apoptotic parameters were
      analyzed for determination of apoptotic pathway in Ishikawa cells treated with 20
      microM or 40 microM raloxifene for 48 h. The numbers of apoptotic cells were
      significantly increased in cells treated with raloxifene as compared with control
      cells. Activities of caspase-3,-8, and-9 were significantly elevated in Ishikawa
      cells treated with raloxifene. A significant decrease in mitochondrial membrane
      potential was observed in this treatment. In addition, the levels of cytosolic
      cytochrome c were significantly elevated in raloxifene-treated cells. Expression
      of Bid was detected in both control and raloxifene-treated cells, but Bid
      cleavage was not observed. In caspase inhibitor experiments, cell viability was
      significantly increased by the caspase-9 inhibitor z-LEHD-fmk and by the caspase
      3 inhibitor z-DEVD-fmk. However, cell viability was unaffected by addition of the
      caspase-8 inhibitor z-IETD-fmk. Thus, raloxifene induced mitochondria-mediated
      apoptosis in endometrial cancer cells but not via the Bid-mitochondria pathway.
      It is possibly that raloxifene may be useful as an adjuvant to current
      chemotherapies for endometrial cancer and possibly is useful as a chemopreventive
      agent.

PMID- 18807139
TI  - Immunoreactivities for glutathione S-transferases and glutathione peroxidase in
      the lateral wall of pigmented and albino guinea pig cochlea.
AB  - Dark-skinned people are known to be more tolerant of ototraumatic noise than are
      light-skinned people, and pigmented animals are more tolerant of ototraumatic
      noise and aminoglycoside ototoxicity than are albino animals. Such tolerance may
      be dependent on the local ability of detoxification and antioxidant enzymes,
      including glutathione S-transferase (GST) and glutathione peroxidase (GSPx). In
      the present study, we examined the difference in GST/GSPx expression in the
      lateral wall of the cochlea between pigmented and albino guinea pigs. Eight-week
      old male pigmented and albino guinea pigs were killed by transcardiac perfusion
      with 2% paraformaldehyde. The cochlear ducts were isolated, further fixed with 4%
      paraformaldehyde, decalcified, and then embedded in paraffin. Sections prepared
      at 5-microm thickness were incubated with anti-GST-alpha,-mu,-pi, or anti-GSPx
      antibody, reacted with Alexa Fluorconjugated secondary antibody, and examined
      under a Carl Zeiss Axioskop 2 plus fluorescence microscope. The cochlea ducts
      were also subjected to immunoelectron microscopy for GST-pi by the postembedment
      method. The stria vascularis of pigmented guinea pigs was strongly immunoreactive
      for GST-alpha,-mu,-pi, and GSPx, whereas no or only weak immunoreactivities were
      seen in the stria vascularis of albino guinea pigs. The spiral ligament showed
      positive but different immunoreactivities for these enzymes between the strains.
      Double-stained immunofluorescence micrographs for GST-pi and GSPx showed a close
      resemblance of localization between the two enzymes in both pigmented and albino
      guinea pigs. At the ultrastructural level, immunoreactivity for GST-pi was
      localized preferentially in the melanin cells of pigmented guinea pigs. These
      results suggest that correlation between pigmentation and inner ear
      susceptibility is, at least partially, attributed to the different distribution
      of GST/GSPx in the stria vascularis.

PMID- 18807140
TI  - Immunohistochemical and electron microscopic characterization of brush cells of
      the rat cecum.
AB  - Brush cells (BCs) are relatively rare cells that are sparsely distributed
      throughout the mammalian digestive and respiratory systems. BCs have been
      identified in the rodent large intestine, but these cells have not been
      characterized by immunocytochemistry or electron microscopy. We previously
      demonstrated that rat bile duct BCs had strong immunoreactivity for six proteins
      that function in HCO(3)(-) secretion and thus assumed that BCs secrete NaHCO(3).
      It is well known that the gastrointestinal (GI) tract secretes NaHCO(3), but it
      is not known whether BCs of the GI tract also express proteins related to HCO(3)(
      ) secretion. Thus, in the present study, using double immunostaining for
      cytokeratin 18, a specific marker for BCs, we investigated protein expression in
      BCs from the rodent GI tract. We show that BCs from the GI tract express six
      proteins related to HCO(3)(-) secretion: cystic fibrosis transmembrane
      conductance regulator (CFTR), Cl(-)/HCO(3)(-) exchanger, Na(+)/HCO(3)(-)
      cotransporter, carbonic anhydrase II, Na(+)/H(+) exchanger (NHE) 1, and NHE3.
      These results suggest that BCs from the GI tract secrete NaHCO(3). In addition,
      we examined BCs from the rat cecum using electron microscopy (EM). Transmission
      EM (TEM) showed that BCs have long microvilli, a well-developed tubulovesicular
      system, and an abundant cytoskeleton. Scanning EM revealed that BCs were
      scattered on the luminal surface of the cecum and had numerous long microvilli.

PMID- 18807141
TI  - Distinct morphological and immunohistochemical features and different growth
      rates among four human neuroblastomas heterotransplanted into nude mice.
AB  - To elucidate more precisely the biological characteristics of neuroblastomas, we
      examined four human neuroblastomas heterotransplanted into athymic nude mice NB
      39 (undifferentiated type), NB-45 (poorly differentiated type with
      undifferentiated component), NB-52 (poorly differentiated type), and NB-726
      (differentiating type) by electron microscopy, immunohistochemistry, and
      radioimmunoassay for the peptides in tumors. Ultrastructurally, NB-45, NB-52, and
      NB-726 contained more numerous and variously sized neurosecretory granules than
      did NB-39. Immunohistochemistry revealed neurofilament proteins, tyrosine
      hydroxylase, neuropeptide Y (NPY), and chromogranin A-positive cells in the four
      tumors in the following order of frequency: NB-726, NB-45, NB-52, and NB-39. NB
      726, NB-45, and NB-52, but not NB-39, contained galanin-positive tumor cells. NB
      45 and NB-726 harbored a few positive cells for calcitonin gene-related peptide.
      Furthermore, NB-726 exhibited positivity to leu-enkephalin, met-enkephalin,
      vasoactive intestinal peptide (VIP), and serotonin. Radioimmunoassay
      substantiated the results of immunohistochemistry, showing NPY in all tumors and
      either galanin or VIP in three tumors, excepting NB-39. Average doubling time of
      the tumor was as follows: 2 days in NB-39, 10 days in NB-45, 22 days in NB-52,
      and 45 days in NB-726. These results indicate that human neuroblastoma cells have
      different biological characteristics and reduced growth rate with differentiation
      in terms of ultrastructure and of peptide production abilities.

PMID- 18807142
TI  - Characteristic cell wall ultrastructure of a macrolide-resistant Staphylococcus
      capitis strain isolated from a patient with chronic sinusitis.
AB  - Fourteen-membered-ring macrolides have an antiinflammatory effect, in addition to
      their antibacterial effect, and are widely used at low dosages for long-term
      therapy for chronic inflammatory disease such as diffuse pan-bronchiolitis and
      chronic sinusitis. A macrolide-resistant coagulase-negative staphylococcal strain
      was obtained from the maxillary sinus of a patient with chronic sinusitis, who
      failed long-term macrolide therapy. The isolated strain was characterized as
      Staphylococcus capitis and had an MIC for erythromycin greater than 128
      microg/ml. Morphological observation demonstrated that this macrolide-resistant
      S. capitis strain had a thicker cell wall than macrolide-sensitive S. capitis
      strains. Moreover, the strain was not carrying any other than the four genes that
      are known mainly to encode for macrolide resistance in S. aureus. Therefore, the
      strain had an unknown macrolide-resistance mechanism that might be related to
      cell wall thickening.

PMID- 18807143
TI  - Signet-ring stromal tumor of the ovary: an immunohistochemical and
      ultrastructural study with a review of the literature.
AB  - Signet-ring stromal tumor is a very rare type of ovarian neoplasm. Only ten cases
      of this tumor have been reported in the English literature. We report here an
      additional case of this type of tumor that arose from the left ovary in a 76-year
      old woman. By light microscopy, the tumor was composed of small round and oval
      cells with cytoplasmic vacuolization and a typical signet-ring appearance,
      focally admixed with fibromatous tissue. Special staining revealed that the
      vacuoles of the tumor cells contained no lipid, mucoprotein, or glycogen.
      Interestingly, variously sized hyaline globule-like structures positive for
      periodic acid-Schiff (PAS) reaction with and without diastase digestion were
      present in the cytoplasm of tumor cells. Immunohistochemically, the tumor cells
      variously expressed several markers, including CD56, inhibin-alpha, alpha-smooth
      muscle actin (alpha-SMA), and progesterone receptor (PR), which have been
      identified in ovarian sex cord-stromal neoplasms. Ultrastructurally, the hyaline
      globule-like structures in tumor cells appeared to be lysosomes, and the vacuoles
      in the cells appeared to have resulted from pseudoinclusions of extracellular
      edematous matrix.

PMID- 18807144
TI  - A case of primary hepatic non-Hodgkin's lymphoma with chronic hepatitis C.
AB  - We report a case of primary hepatic non-Hodgkin's lymphoma in a 67-year-old man
      with chronic hepatitis C. Laboratory data revealed slightly elevated liver
      function parameters and positive for hepatitis C virus (HCV) antibody. Abdominal
      ultrasonography showed hypoechoic lesions approximately 5 mm in diameter in the
      whole liver. Magnetic resonance imaging showed that the tumors were isointense in
      relationship to the liver on T(1)-weighted images but were slightly hyperintense
      on T(2)-weighted images. Under a clinical diagnosis of liver tumor, liver biopsy
      was performed. Histological examination confirmed a diagnosis of non-Hodgkin's
      diffuse large B-cell lymphoma, and the immunophenotype was identified to be the
      germinal cell type.

PMID- 18807145
TI  - A rare case of coexistence of pulmonary adenocarcinoma with Langerhans' cell
      histiocytosis.
AB  - We report a rare case of coexisting pulmonary adenocarcinoma and Langerhans' cell
      histiocytosis (LCH) in a 78-year-old woman who did not smoke. During follow-up of
      diabetes mellitus, she had complained of chest pain and was found to have a
      nodular lesion in S9 of the left lower lobe, which was resected surgically. No
      abnormal laboratory findings were obtained. Before surgical resection, needle
      biopsy specimens confirmed the existence of adenocarcinoma. The resected tumor in
      the left lower lobe was 3.0 x 1.8 x 3.0 cm, and histologically both acinar and
      bronchioloalveolar cell subtypes of adenocarcinoma were found in cancer foci. In
      addition to pulmonary adenocarcinoma, Langerhans' cell proliferation associated
      with marked eosinophil infiltration was incidentally found in a small nodule,
      approximately 3 x 2 mm in size in the subpleural region. The Langerhans' cells
      contained interdigitated nuclei, exhibiting rather clear nucleoplasm and
      cytoplasm; they were positive for S-100 protein, CD1a, and also CD4. Massive
      eosinophil infiltration was found around the focus of Langerhans' cell
      proliferation. This nodule appeared to be LCH. The adenocarcinoma and LCH were
      adjacent, and cancer cells were infiltrated only in the peripheral parts of LCH.
      The coexistence of adenocarcinoma and LCH appeared to be incidental. The
      association of adenocarcinoma and LCH is rare, and only several reports of it can
      be found in the English literature.

PMID- 18807146
TI  - Elastofibroma: a histochemical, immunohistochemical, and ultrastructural study of
      two patients.
AB  - Elastofibroma is a rare neoplasm. In this article, we report our study of the
      pathogenesis of fibrosis in elastofibroma. Three tumors obtained from two
      patients were selected. One patient was a 57-year-old Japanese woman who had a
      bilateral tumor, and the other patient was a 83-year-old Japanese man. All tumors
      occurred in the infrascapular region. Macroscopically, the cut surface of all
      tumors showed a poorly defined and whitish mass with yellowish foci.
      Microscopically, the tumor consisted of collagen fiber bundles, abnormal elastic
      fibers, and spindle cells suggestive of fibroblasts. Elastica-van Gieson and
      Masson-trichrome stain identified abnormal elastic fibers and abundant collagen
      fibers, respectively, in elastofibroma. Immunohistochemically, fibroblasts were
      positive for CD34 but negative for alpha-smooth muscle actin and h-caldesmon.
      Additionally, the cytoplasm of many fibroblasts was positive for TGF-beta in all
      tumors. Ultrastructurally, some fibroblasts with abundant organelles in one tumor
      were observed in the adjacent area to amorphous elastic mass and bundles of
      collagen fibers. However, no myofibroblasts were ultrastructurally identified in
      the tumor. Finally, our study supplies further evidence that elastofibroma may
      show the proliferation of CD34-positive fibroblasts and contain no
      myofibroblasts, and that fibroblasts may produce both abnormal elastic fibers and
      collagen fibers through the secretion of TGF-beta.

PMID- 18807147
TI  - How to handle low-molecular-weight heparins in patients with decreased renal
      function: an open issue.

PMID- 18807148
TI  - Attitude of the Italian general population towards prevention and screening of
      the most common tumors, with special emphasis on colorectal malignancies.
AB  - Screening and early diagnosis of cancer represent relatively recent tools in the
      long-lasting battle against tumors. If the American public opinion manifests its
      enthusiasm towards screening, the attitude of European is less well known. The
      purpose of the present study was to assess the level of knowledge and awareness
      of cancer screening (with particular emphasis on colorectal neoplasms) among
      middle-aged individuals. The study group consisted of 945 healthy individuals
      (489 men, 456 women, average age 57 +/- 12.4 years) who were asked to answer a
      series of questions about cancer screening and surveillance through a
      questionnaire presented by trained residents. Each interview lasted 20-30 min.
      Middle-aged Italians of both sexes seem to be aware of the fact that cancer is a
      frequent disease; moreover, many of the interviewed subjects believe almost all
      neoplasms are incurable. Diet, style of life, other environmental factors and
      familial factors are fully appreciated as relevant risk factors. The exact
      meaning of prevention was clear to less than half of the subjects. When various
      cancer sites were analyzed, the existence of preventive measures was well known
      for breast, cervical and prostate tumors, but their role was less clear for
      colorectal cancer. Only a fraction of the interviewed individuals were willing to
      undergo screening; the main reasons for refusal were lack of usefulness and fear
      of results. Among various tests, ultrasound and endoscopy were usually carried
      out in the presence of symptoms. Finally, multivariate analysis showed that the
      two factors significantly associated with the decision to undergo screening
      procedures were increasing age and level of education. The results of the study
      suggest that middle-aged Italian individuals, predominantly from Northern
      regions, have a correct perception of some aspects (frequency, risk factors) of
      cancer biology, whereas the knowledge of other aspects (outcome, prevention)
      remains poor or approximate. It follows that one of the main objectives of the
      Political Class should be to obtain a better education of overage individuals
      about cancer and the many problems related to this common disease.

PMID- 18807149
TI  - Hypofractionated stereotactic radiotherapy in combination with whole brain
      radiotherapy for brain metastases.
AB  - BACKGROUND: The efficacy and toxicity of hypofractionated stereotactic
      radiotherapy (HSRT) in combination with whole brain radiotherapy (WBRT), for the
      treatment of 1-4 brain metastases, using a non invasive fixation of the skull,
      was investigated. METHODS: Between 04/2001 and 01/2006 30 patients with 44 brain
      metastases underwent irradiation. Every patient received WBRT (10 x 3 Gy); 41/44
      lesions received HSRT boost with a median dose fraction of 6 Gy, the
      fractionation schemes were 3 x 6 Gy and 4 x 8 Gy; a median total dose of 18 Gy
      was delivered to the tumor isocenter. RESULTS: The median survival period was
      9.15 months, the actuarial 1-year overall survival and freedom from new brain
      metastases were 36.6% and 87.9%, respectively; at univariate analysis Karnofsky
      Performance Status (KPS) was statistically significant (P = 0.05); the actuarial
      1-year local control for the 41/44 lesions was 86.1%. No patient had acute or
      late complications. CONCLUSIONS: HSRT as a concomitant boost during WBRT is a
      safe and well tolerated treatment for selected patients with brain metastases.

PMID- 18807150
TI  - Rapid biofabrication of tubular tissue constructs by centrifugal casting in a
      decellularized natural scaffold with laser-machined micropores.
AB  - Centrifugal casting allows rapid biofabrication of tubular tissue constructs by
      suspending living cells in an in situ cross-linkable hydrogel. We hypothesize
      that introduction of laser-machined micropores into a decellularized natural
      scaffold will facilitate cell seeding by centrifugal casting and increase
      hydrogel retention, without compromising the biomechanical properties of the
      scaffold. Micropores with diameters of 50, 100, and 200 mum were machined at
      different linear densities in decellularized small intestine submucosa (SIS)
      planar sheets and tubular SIS scaffolds using an argon laser. The ultimate stress
      and ultimate strain values for SIS sheets with laser-machined micropores with
      diameter 50 mum and distance between holes as low as 714 mum were not
      significantly different from unmachined control SIS specimens. Centrifugal
      casting of GFP-labeled cells suspended in an in situ cross-linkable hyaluronan
      based hydrogel resulted in scaffold recellularization with a high density of
      viable cells inside the laser-machined micropores. Perfusion tests demonstrated
      the retention of the cells encapsulated within the HA hydrogel in the microholes.
      Thus, an SIS scaffold with appropriately sized microholes can be loaded with
      hydrogel encapsulated cells by centrifugal casting to give a mechanically robust
      construct that retains the cell-seeded hydrogel, permitting rapid biofabrication
      of tubular tissue construct in a "bioreactor-free" fashion.

PMID- 18807151
TI  - Synthesis, neutralization and blocking procedures of organic/inorganic hybrid
      scaffolds for bone tissue engineering applications.
AB  - Bioactive glasses (BaG) can bind to human bone tissues and have been used in many
      biomedical applications for the last 30 years. However they usually are weak and
      brittle. On the other hand, composites that combine polymers and BaG are of
      particular interest, since they often show an excellent balance between stiffness
      and toughness. Bioactive glass-poly(vinyl alcohol) foams to be used in tissue
      engineering applications were previously developed by our group, using the sol
      gel route. Since bioactive glass-polymer composite derived from the sol-gel
      process cannot be submitted to thermal treatments at high temperatures (above 400
      degrees C), they usually have unreacted species that can cause cytotoxicity. This
      work reports a technique for stabilizing the sol-gel derived bioactive
      glass/poly(vinyl alcohol) hybrids by using glutaraldehyde (GA), NH(4)OH solutions
      and a blocking solution containing bovine serum albumin. PVA/BaG/GA hybrids were
      characterized by Fourier Transform Infrared Spectroscopy (FTIR) and Scanning
      Electron Microscopy (SEM/EDX) analyses. Moreover, MTT (3-[4,5-dimethylthiazole-2
      yl]-2,5-diphenyltetrazolium bromide) biocompatibility and cytotoxicity assays
      were also conducted. The hybrids exhibited pore size varying from 80 to 820 mum.
      After treatments, no major changes in the pore structure were observed and high
      levels of cell viability were obtained.

PMID- 18807152
TI  - Preparation and characterization of diazeniumdiolate releasing ethylcellulose
      films.
AB  - A monolayer and trilayer membrane configuration of ethylcellulose were doped with
      a new synthesized diazeniumdiolate GAGS/NO (glutaraldehyde modification of
      glucosamine/NO adduct) and DETA/NO as the NO donor species, which can be used for
      altering the time course of nitric oxide donor release and targeting it to
      tissues with which the polymers are in physical contact. The NO donor release
      profiles show that the average release rate of DETA/NO can be controlled from 0.2
      to 9 x 10(-10)mol cm(-2) min(-1) for at least 7 day and up to 30 day under
      physiological condition. The average release rate of GAGS/NO is varied from 0.1
      to 0.5 x 10(-10)mol cm(-2) min(-1) for up to 94 day. The trilayer configuration
      effectively eliminates the burst release in the initial stage, and notably
      increases the NO donor release time. The trilayer films of DETA/NO can release 5%
      of the total NO donors over 69 h. In comparison, the trilayer films of GAGS/NO
      only release 2.5% of the total NO donors over 69 h. The results suggest that this
      nitric oxide donor releasing polymer may hold considerable promise for reducing
      the risk of restenosis following angioplasty and other interventional procedures
      for vascular repair.

PMID- 18807154
TI  - Performance of fluorescent labels in sedimentation bead arrays--a comparison
      study.
AB  - An extensive study is described to identify the most suitable fluorescent label
      in magnetic microsphere sedimentation arrays. The investigated fluorescent
      labels, commonly used in multiplex analysis, include organic dyes, (fluorescein,
      Alexa488, Cy5) fluorescent proteins (R-Phycoerythrin, Allophycocyanine, PBXL-3)
      polymer nanoparticles (FluoSpheres, PD-Pt) and semiconductor nanocrystals
      (Quantum dots). DNA hybridization assays on magnetic microspheres were applied as
      model systems to reveal label performance. The fluorescent labels were
      characterized under optimized conditions regarding signal intensity, non-specific
      binding and photo-stability. The advantages and drawbacks of individual labels
      are discussed. The limit of detection and dynamic ranges are determined to
      compare the performance of selected labels. Detection limits of 2 x 10(-10) mol/L
      are found for the determination of oligonucleotides using PBXl-3 as label, which
      is comparable with typical flow cytometer systems. The results and protocols are
      highly valuable for any type of bead based assays and can be easily transferred.

PMID- 18807155
TI  - Long-term neurocognitive function of pediatric patients with severe combined
      immune deficiency (SCID): pre- and post-hematopoietic stem cell transplant
      (HSCT).
AB  - BACKGROUND: Hematopoietic stem cell transplantation (HSCT) is the only cure for
      patients with severe combined immunodeficiency (SCID). The purpose of this study
      was to evaluate long-term neurodevelopment of patients with SCID following
      myeloablative chemotherapy and HSCT. MATERIALS AND METHODS: Sixteen pediatric
      patients diagnosed with SCID were tested using the Bayley Scales of Infant
      Development and the validated Vineland Adaptive Behavior Scales (VABS) pre- and 1
      year post-HSCT. Three years post-HSCT, there were 11 patients available for
      testing and four patients available 5 years post-HSCT. Patients greater than 3
      years of age were administered the Wechsler Preschool and Primary Scale of
      Intelligence. Both raw scores and scaled scores were analyzed. RESULTS: There was
      a significant decrease 1 year post-HSCT in the Bayley Mental Developmental Index
      (MDI) [92.5 (pre) vs. 70.81 (1 year post), p < 0.0001] and the VABS [99.73 (pre)
      vs. 79.87 (1 year post), p = <0.0001]. There was a significant decrease over time
      in the MDI [95.00 (pre) vs. 72.64 (1 year post) vs. 71.82 (3 years post), p <
      0.0001], but no significant change between 1 and 3 years post-HSCT. There was no
      change in the Bayley Psychomotor Development Scale (PDI) [82.4 (pre) vs. 84.8 (1
      year post), p = 0.68]. The PDI scores decreased over time [86.29 (pre) vs. 86 (1
      year post) vs. 74.14 (3 years post), p = 0.045]. Although there was a decrease in
      scaled scores, there was not a loss of skills. Analysis of raw scores showed that
      there was an increase in the raw test scores, which indicated that these children
      acquired developmental skills, but at a slower rate than normal infants and
      toddlers. Younger children had a more significant decrease in adaptive scores
      compared with older children. CONCLUSIONS: These findings may reflect the effects
      of the isolation and prolonged hospitalization that characterizes the immediate
      post-transplant period. Patients miss out on social interactions and learning
      opportunities that normally occur at their respective stages of development.
      These restrictions keep patients from acquiring developmentally appropriate
      cognitive skills as well as gross and fine motor developmental milestones.
      Longitudinal follow-up will be important to quantify acquisition of skills.

PMID- 18807157
TI  - Gender, suicide, and the sociocultural context of deliberate self-harm in an
      urban general hospital in Mumbai, India.
AB  - Recognizing the complementary effects of social contexts and psychiatric
      disorders, this study clarifies the role of gender in suicidal behavior in urban
      Mumbai by considering psychiatric diagnoses and patient-identified sociocultural
      features. The cultural epidemiological approach suggests the critical impact of
      situational sociocultural factors that complement the customary
      psychopathological accounts for those who harm or kill themselves. The cultural
      epidemiology of deliberate self-harm (DSH), it is argued, is critical to planning
      for suicide prevention, community mental health and psychiatric practice. This
      study, based on a cultural epidemiological framework, compares male and female
      admissions for DSH, evaluating conditions with SCID-I and EMIC interviews. We
      assessed features and narratives of suicidal behavior, patient-identified
      underlying problems, their perceived causes and triggers. The study included 92
      women and 104 men. A diagnosis of depressive disorder was made for 48.9 percent
      of women and 39.4 percent of men. Many patients (50.0 percent of women and 41.3
      percent of men) did not fulfill the criteria for any diagnosis, or did so only
      for an adjustment disorder or a V-code. Men typically explained DSH with
      reference to work problems, financial problems and problem drinking. Women
      typically discussed domestic problems, in-law relations and victimization.
      Problem drinking affected women living with men who drank. Social and situational
      factors appear to play a relatively greater role than psychiatric illness in self
      harm and suicide in Mumbai, as in other Asian studies, compared with Europe and
      North America.

PMID- 18807158
TI  - Hippocampal extracellular GABA correlates with metabolism in human epilepsy.
AB  - As the major inhibitory neurotransmitter in human brain, GABA is an important
      modulator of hyperexcitability in epilepsy patients. Given the high energetic
      cost of neurotransmission and synaptic activity, GABA concentrations may be
      hypothesized to correlate with metabolic function. We studied human epilepsy
      patients undergoing intracranial EEG monitoring for seizure localization to
      examine microdialysis measures of extracellular GABA (ecGABA), pre-operative MR
      spectroscopic measures of neuronal mitochondrial function (NAA/Cr), and wherever
      possible, neuropathology and hippocampal volumetry. Two groups undergoing
      intracranial monitoring for seizure localization were studied: surgically treated
      hippocampal epilepsy (MTLE) and neocortical (non-hippocampal seizure onset)
      epilepsy. All data are hippocampal and thus these groups allow comparisons
      between the epileptogenic and non-epileptogenic regions. ecGABA was measured
      using in vivo microdialysis performed during intracranial monitoring. Pre
      operative in vivo MR spectroscopic imaging was performed to measure the ratio of
      N-acetyl aspartate (NAA) to creatine. Standard methods for neuropathology and
      hippocampal volumetry were used. In the neocortical group, increased ecGABA
      correlated with greater NAA/Cr (R = +0.70, p < 0.015, n = 12) while in the MTLE
      group, increased ecGABA linked with decreased NAA/Cr (R = -0.94, p < 0.001, n =
      8). In MTLE, ecGABA (increased) and NAA/Cr (decreased) correlated with increased
      glial cell numbers (R = +0.71, p < 0.01, n = 12, R = -0.76 p < 0.03
      respectively). No relationship was seen between ecGABA and hippocampal volumes in
      either group. In epilepsy, ecGABA increases occur across a range of metabolic
      function. Outside the seizure focus, ecGABA and NAA/Cr increase together; in
      contrast, within the seizure focus, ecGABA increases with declining mitochondrial
      function.

PMID- 18807159
TI  - Establishment of the insulin resistance induced by inflammatory response in 3T3
      L1 preadipocytes cell line.
AB  - In the light of given recent reports, insulin resistance related to inflammation
      is characterized by increasing a diverse array of pro-inflammatory cytokines. In
      this study, hypothesizing that 3T3-L1 non-differentiated preadipocytes cell line
      as a cell model could be used to investigate this linkage, the aim is to
      determine whether the preadipocytes induced by different inflammatory responses
      could cause insulin resistance. This paper has determined the time and
      concentration-dependent effects of insulin on glucose consumption in the 3T3-L1
      non-differentiated preadipocytes. Glucose consumption has also been assayed in
      the preadipocytes which are treated with LPS and CM originated from LPS-activated
      RAW264.7. Then protein level of each group has been measured by coomassie
      brilliant blue protein kit. Furthermore, secretion levels of IL-6 and TNF-alpha
      are measured by ELISA in the supernatant of RAW264.7 and preadipocytes. Finally,
      the mRNA expressions for IL-6, TNF-alpha and PPARgamma has been assessed by RT
      PCR. The results show that administration of LPS and CM both can increase
      releases of IL-6 and TNF-alpha, as well as gene expression of IL-6 mRNA; this
      change is accompanied with suppression of PPARgamma mRNA activation in 3T3-L1
      undifferentiated preadipocytes. In conclusion, our results suggest that in
      preadipocytes, pro-inflammatory cytokines can result in insulin resistance, and
      deserve further investigation to be helpful for treatment and revealing
      mechanisms of T2DM.

PMID- 18807160
TI  - Glutamine reduces TNF-alpha by enhancing glutathione synthesis in
      lipopolysaccharide-stimulated alveolar epithelial cells of rats.
AB  - To investigate the role of glutathione (GSH) synthesis in the regulation on
      nuclear factor (NF)-kappaB activity and tumor necrosis factor-alpha (TNF-alpha)
      release by glutamine (GLN) in lipopolysaccharide (LPS)-stimulated alveolar type
      II (AT-II) epithelial cells of rat lungs. Primary cultured AT-II cells were pre
      treated with various doses of GLN for 2, 8, 16, 24 h. At the 8 h time point
      before LPS stimulation, various doses of L: -buthionine-(S,R)-sulfoximine (BSO),
      an inhibitor of GSH synthesis, were added with 10 mM GLN. Then the cells were
      stimulated with 1 mug/ml LPS for 24 h. The cells were obtained for GSH
      measurement. TNF-alpha level in the supernatant was determined by enzyme-linked
      immunosorbent assay. NF-kappaB activity was assessed by electrophoretic mobility
      shift assay. Eight hours before LPS exposure was the best time point for GLN's
      enhancing GSH synthesis. LPS could significantly decrease the GSH level, increase
      NF-kappaB activation and TNF-alpha release in AT-II cells. Supplementation of GLN
      could increase the GSH level and attenuate the release of TNF-alpha in LPS
      stimulated AT-II cells in a dose-dependant manner. And NF-kappaB activation also
      could be prevented by GLN. BSO could block the effect of GLN. As a precursor of
      GSH, glutamine could prevent the NF-kappaB activation and attenuate the release
      of TNF-alpha in LPS-stimulated AT-II cells and the effect may be mediated via GSH
      synthesis.

PMID- 18807161
TI  - Long-term efficacy of delayed cure after circumferential pulmonary vein ablation
      of atrial fibrillation.
AB  - INTRODUCTION: The reliability of delayed cure of early recurrence of atrial
      fibrillation (ERAF) is still undetermined. Furthermore, the predictors of
      recurrence after delayed cure of ERAF are less investigated in depth. AIMS OF THE
      STUDY: The purpose of this study was to investigate the long-term efficacy of
      delayed cure of ERAF after catheter ablation of AF and explore the he predictors
      of recurrence after delayed cure of ERAF. METHODS AND RESULTS: We prospectively
      studied 300 consecutive patients with atrial fibrillation (AF) who were referred
      for circumferential pulmonary vein ablation (CPVA). After a follow-up of 19.2 +/-
      4.1months, of the 87 patients with early recurrence of AF 41 achieved delayed
      cure, 11 of them reoccurred AF subsequently. Univariate analysis showed that
      persistent AF, absence of pulmonary vein (PV) isolation and external
      cardioversion were related to reoccurrence after delayed cure. Logistic
      regression analysis identified only absence of PV isolation as a predictor of
      recurrent AF after delayed cure. CONCLUSIONS: Delayed cure after CPVA is
      relatively common and its efficacy at long-term follow-up is reasonably
      consistent. However, in patients without PV isolation, delayed cure is unstable
      and the risk of late recurrence is increased.

PMID- 18807162
TI  - Change detection in naturalistic pictures among children with autism.
AB  - Persons with autism often show strong reactions to changes in the environment,
      suggesting that they may detect changes more efficiently than typically
      developing (TD) persons. However, Fletcher-Watson et al. (Br J Psychol 97:537
      554, 2006) reported no differences between adults with autism and TD adults with
      a change-detection task. In this study, we also found no initial differences in
      change-detection between children with autism and NVMA-matched TD children,
      although differences emerged when detection failures were related to the
      developmental level of the participants. Whereas detection failures decreased
      with increasing developmental level for TD children, detection failures remained
      constant over the same developmental range for children with autism, pointing to
      an atypical developmental trajectory for change-detection among children with
      autism.

PMID- 18807163
TI  - Sequence variability and phylogenetic relationship of betasatellite isolates
      associated with yellow vein mosaic disease of mesta in India.
AB  - Six betasatellite isolates associated with the yellow vein mosaic disease in
      mesta crops grown under three different geographical locations of India have been
      characterized. These six isolates and the one previously reported from eastern
      India could be divided into two distinct Types. The first Type, consisted of four
      betasatellite isolates characterized from northern and southern regions of India,
      was observed to be the newer isolates of Ludwigia leaf distortion betasatellite.
      The second Type, comprised three betasatellite isolates obtained from the eastern
      part of India, showed highest sequence identity with Cotton leaf curl Multan
      betasatellite and appeared to be the newer isolates of it. These isolates present
      within each of these two betasatellite species showed limited variability with
      respect to their individual group. The results thus indicated the association of
      two different betasatellite species with yellow vein mosaic disease of mesta in
      India and highlighted the possible adaptation of mesta crops as a newer hosts by
      these two betasatellite species.

PMID- 18807164
TI  - Being 'at-risk' for developing cancer: cognitive representations and
      psychological outcomes.
AB  - This study investigated cognitive representations and psychological effects of
      being 'at-risk' for cancer. Perceived personal risk for cancer and causal
      attributions for cancer were measured in four groups: women identified as
      carriers of mutations in breast/ovarian cancer genes BRCA1 BRCA2, habitual
      smokers, X-ray technicians, and an average-risk group. Despite differences in
      awareness of their risk status and perceived risk for cancer, the groups did not
      differ in health anxiety, cancer worry interference, and self-assessed health.
      Motivated reasoning processes were identified as potential strategies used by
      individuals at-risk to regulate levels of psychological distress. Evidence for
      biased risk perceptions and unrealistic optimism were found among smokers, and
      patterns indicative of self-enhancement through self-assessments and defensive
      discounting of cancer causal attributions were found in the genetically
      susceptible group. These findings highlight the role of cognitive representations
      in adjustment to being at-risk for cancer.

PMID- 18807165
TI  - Early childhood adversities and trajectories of psychiatric problems in adoptees:
      evidence for long lasting effects.
AB  - The aim of the present study is to investigate whether early childhood
      adversities determine the longitudinal course of psychiatric problems from
      childhood to adulthood; in particular if the impact of early maltreatment on
      psychopathology decreases as time passes. A sample of 1,984 international
      adoptees was followed (955 males and 1029 females; adopted at the mean age of 29
      months). Parents provided information about abuse, neglect and number of
      placements prior to adoption at baseline and completed the Child Behavior
      Checklist or the Young Adult Behavior Checklist three times when their children
      were between 10 and 30 years of age. Multilevel analyses were performed to
      determine trajectories of psychiatric problems. Experience of early childhood
      adversity prior to adoption substantially increased the level of psychiatric
      problems, especially when maltreatment was severe. Moreover, the impact of early
      adversities on psychiatric problems remained markedly stable. This suggests that
      vulnerability of early-maltreated children persists even if they are taken out of
      their problematic environments and are raised in enriched circumstances.

PMID- 18807166
TI  - New directions in measuring reactive and proactive aggression: validation of a
      teacher questionnaire.
AB  - The well-known distinction between reactive and proactive aggression is
      theoretically important but empirically controversial. Recently, aggression
      researchers have argued that we should separate the form and function of
      aggression to make a clearer distinction between reactive and proactive
      aggression. This article describes the validation of a new teacher-report
      Instrument for Reactive and Proactive Aggression (IRPA) that assesses the form
      separate from the function of aggression. We demonstrated good discriminant,
      convergent, and construct validity of the IRPA in a sample of 427 children aged
      10 to 13. Reactive and proactive functions of aggression were independent
      constructs (r = 0.03) which indicates excellent discriminant validity. Convergent
      validity was satisfactory; scores from the IRPA were moderately to highly related
      to scores from the widely used Teacher Rating Instrument, TRI (Dodge and Coie in
      Journal of Personality and Social Psychology 53:1146-1158, 1987). Additionally,
      reactive and proactive aggression showed unique correlations with most a priori
      hypothesized theoretically relevant variables, which indicates construct
      validity. (150 words).

PMID- 18807167
TI  - Role of genetic recombination in the molecular architecture of Papaya ringspot
      virus.
AB  - Papaya ringspot virus (PRSV) has a single-stranded RNA genome and causes severe
      economic losses both in cucurbits and papaya worldwide. The extent to which the
      genome of PRSV is shaped by recombination provides an understanding of the
      molecular evolution of PRSV and helps in studying features such as host
      specificity, geographic distribution, and its emergence as new epidemics. The
      PRSV-P-Indian isolate was completely sequenced and compared with 14 other
      isolates reported from the rest of the world for their phylogenetic survey of
      recombination events. Cistron-by-cistron sequence comparison and phylogenetic
      analysis based on full-genome polyprotein showed two distinct groupings of Asian
      and American isolates, although PRSV-P and W-India clustered along with the
      American isolates. Recombination sites were found throughout the genomes, except
      in the small 6K1 protein gene. A significant proportion of recombination hotspots
      was found in the P1 gene, followed by P3, cylindrical inclusion (CI), and helper
      component proteinase (HcPro). Correlations between the presence of recombination
      sites, geographic distribution, and phylogenetic relationship provide an
      opportunity to establish the molecular evolution and geographic route of PRSV.

PMID- 18807168
TI  - Novel SNPs of the bovine LEPR gene and their association with growth traits.
AB  - In this study, polymorphism in the bovine LEPR gene exon 4 was detected by PCR
      SSCP and DNA sequencing methods in 653 individuals from five Chinese cattle
      breeds. Two haplotypes (M and N), three observed genotypes (MM, MN, and NN), and
      five single nucleotide polymorphisms (SNPs) (NC_007301:g.26767T>C,
      NC_007301:g.26805C>T, NC_007301:g.27050A>G, NC_007301:g.27063G>A,
      NC_007301:g.27079G>A) were detected. The frequencies of haplotypes M and N in the
      five breeds were 0.661-0.747 and 0.253-0.339, respectively. The SNP locus was in
      Hardy-Weinberg equilibrium in Nanyang, Jiaxian red, Angus, and Jinnan cattle (P >
      0.05) and was in Hardy-Weinberg disequilibrium in Qinchuan cattle (P < 0.05).
      Polymorphism of the LEPR gene was shown to be associated with growth traits in
      the Nanyang breed. The SNP in the bovine LEPR gene had significant effects on
      body height, body length, body weight, heart girth, and average daily gain at 6
      and 12 months old (P < 0.01 or P < 0.05). Therefore, these results suggest that
      the LEPR gene is a strong candidate gene that affects growth traits in cattle.

PMID- 18807169
TI  - A novel mitochondrial heteroplasmic C13806A point mutation associated with
      Iranian Friedreich's ataxia.
AB  - Friedreich's ataxia (FRDA) is an autosomal recessive neurodegenerative disorder
      caused by decreased expression of the protein Frataxin. Frataxin deficiency leads
      to excessive free radical production and dysfunction of chain complexes.
      Mitochondrial DNA (mtDNA) could be considered a candidate modifier factor for
      FRDA disease, since mitochondrial oxidative stress is thought to be involved in
      the pathogenesis of this disease. It prompted us to focus on the mtDNA and
      monitor the nucleotide changes of genome which are probably the cause of
      respiratory chain defects and reduced ATP generation. We searched about 46% of
      the entire mitochondrial genome by temporal temperature gradient gel
      electrophoresis (TTGE) and DNA fragments showing abnormal banding patterns were
      sequenced for the identification of exact mutations. In 18 patients, for the
      first time, we detected 26 mtDNA mutations; of which 5 (19.2%) was novel and 21
      (80.8%) have been reported in other diseases. Heteroplasmic C13806A polymorphisms
      were associated with Iranian FRDA patients (55.5%). Our results showed that NADH
      dehydrogenase (ND) genes mutations in FRDA samples were higher than normal
      controls (P < 0.001) and we found statistically significant inverse correlation
      (r = -0.8) between number of mutation in ND genes and age of onset in FRDA
      patients. It is possible that mutations in ND genes could constitute a
      predisposing factor which in combination with environmental risk factors affects
      age of onset and disease progression.

PMID- 18807170
TI  - Alteration of DBP levels in CSF of patients with MS by proteomics analysis.
AB  - OBJECTIVE: The diagnosis of multiple sclerosis (MS) is still challenging recently
      due to the lack of a specific diagnostic test. Proteomics analysis was applied to
      biomarkers discovery and their pathways study. METHODS: First, the proteins of
      CSF from MS patients and control group were analyzed individually with 2D-DIGE
      technology (two-dimensional difference gel electrophoresis). Then, protein spots
      were found out with DeCyder6.0 software which showed different expression levels
      in the gel images between the two groups. The information regarding these
      proteins was collected based on MALDI-TOF/MS and related database searches.
      Lastly, interaction between these proteins was further analyzed by using Metacore
      software. RESULTS: There were 13 proteins that showed more than 1.5-fold
      difference in expression levels between the two groups. Furthermore, the
      identification made by MALDI-TOF/MS revealed that one of the most significant
      differential proteins was DBP (vitamin D-binding protein), which decreased in the
      experimental group. This result was confirmed by ELISA (P < 0.01). Moreover,
      network between the 13 proteins were partially got, which showed some biological
      interactions. CONCLUSION: These results support a correlation between the level
      of DBP and MS. DBP may be a potential useful biomarker for diagnosis or a
      medicine target for treatment of MS.

PMID- 18807171
TI  - Role of STIM1 in regulation of store-operated Ca2+ influx in pheochromocytoma
      cells.
AB  - Changes in the local environment such as pH (acidosis/alkalosis), temperature
      (hypothermia/hyperthermia), and agonist (glutamate) can adversely affect neuronal
      function, and are important factors in clinical situations such as anesthesia and
      intensive care. Regulation of intracellular Ca2+ ([Ca2+](i)) is key to neuronal
      function. Stromal interaction molecule (STIM1) has been recently recognized to
      trigger store-operated Ca2+ entry (SOCE), an important component of [Ca2+](i)
      regulation. Using differentiated, fura-2 loaded rat pheochromocytoma (PC12) cells
      transfected with small interference RNA for STIM1 (or vehicle), we examined the
      role of STIM1 in SOCE sensitivity to temperature, pH, and glutamate. SOCE was
      triggered following endoplasmic reticulum depletion. Cells were washed and
      exposed to altered pH (6.0-8.0), altered temperature (34-40 degrees C), or to
      glutamate. In non-transfected cells, SOCE was inhibited by acidosis or
      hypothermia, but increased with alkalosis and hyperthermia. Increasing glutamate
      concentrations progressively stimulated SOCE. STIM1 siRNA decreased SOCE at
      normal temperature and pH, and substantially decreased sensitivity to acidosis
      and hypothermia, eliminating the concentration-dependence to glutamate.
      Sensitivity of SOCE to these environmental parameters was less altered by
      decreased extracellular Ca2+ alone (with STIM1 intact). We conclude that STIM1
      mediates exquisite susceptibility of SOCE to pH, temperature, and glutamate:
      factors that can adversely affect neuronal function under pathological
      conditions.

PMID- 18807172
TI  - Molecular analysis of endoplasmic reticulum stress response after global
      forebrain ischemia/reperfusion in rats: effect of neuroprotectant simvastatin.
AB  - Simvastatin is a cholesterol-lowering agent whose functional significance and
      neuroprotective mechanism in ischemic brain injury is not yet solved. The purpose
      of this study is to evaluate the effect of simvastatin on ischemic brain injury.
      We examined the endoplasmic reticulum stress response (UPR/unfolded protein
      response), by measuring the mRNA and protein levels of specific genes such as
      ATF6, GRP78, and XBP1 after 15 min 4-VO ischemia and different times of
      reperfusion (1, 3, and 24 h). The results from the group of naive ischemic rats
      were compared with results from the group of pre-treated animals with
      simvastatin. The results of the experiments showed significant increase in all
      genes at the mRNA level in ischemic phase (about 43% for XBP1, 58% for GRP78, and
      39% for ATF6 more than control). The protein level of XBP1 was decreased in pre
      treated animals at ischemic phase and first hour of reperfusion (about 15% less),
      and did not reach control levels. The protein levels of GRP78 were maximal at
      third hour of reperfusion in statin group with a small decrease at 24 h of
      reperfusion in both groups. The levels of ATF6 mRNA in statin-treated animals was
      higher in comparison to non-statin animals at the ischemic phase and the third
      hour of reperfusion (about 35% higher), which was also translated into the higher
      protein level. This could indicate that one of the main proteins targeted to
      enhance neuroprotective effect to ER during the first two hours of reperfusion
      was ATF6 protein, the levels of which were 60% higher than in non-treated
      animals. These data suggest that simvastatin, in addition to the proposed
      neuroprotective effect, exerts a neuroprotective role in the attenuation of ER
      stress response after acute ischemic/reperfusion insult.

PMID- 18807173
TI  - Neural agrin changes the electrical properties of developing human skeletal
      muscle cells.
AB  - Recent investigations suggest that the effects of neural agrin might not be
      limited to neuromuscular junction formation and maintenance and that other
      aspects of muscle development might be promoted by agrin. Here we tested the
      hypothesis that agrin induces a change in the excitability properties in primary
      cultures of non-innervated human myotubes. Electrical membrane properties of
      human myotubes were recorded using the whole-cell patch-clamp technique. Cell
      incubation with recombinant chick neural agrin (1 nM) led to a more negative
      membrane resting potential. Addition of strophanthidin, a blocker of the
      Na(+)/K(+) ATPase, depolarized agrin-treated myotubes stronger than control,
      indicating, in the presence of agrin, a higher contribution of the Na(+)/K(+)
      ATPase in establishing the resting membrane potential. Indeed, larger amounts of
      both the alpha1 and the alpha2 isoforms of the Na(+)/K(+) ATPase protein were
      expressed in agrin-treated cells. A slight but significant down-regulation of
      functional apamin-sensitive K(+) channels was observed after agrin treatment.
      These results indicate that neural agrin might act as a trophic factor promoting
      the maturation of membrane electrical properties during differentiation,
      confirming the role of agrin as a general promoter of muscle development.

PMID- 18807174
TI  - p75NTR antagonistic cyclic peptide decreases the size of beta amyloid-induced
      brain inflammation.
AB  - Amyloid beta (Abeta) was shown to bind the 75 kD neurotrophin receptor (p75(NTR))
      to induce neuronal death. We synthesized a p75(NTR) antagonistic peptide
      (CATDIKGAEC) that contains the KGA motif that is present in the toxic part of
      Abeta and closely resembles the binding site of NGF for p75(NTR). In vivo
      injections of Abeta into the cerebral cortex of B57BL/6 mice together with the
      peptide produced significantly less inflammation than simultaneous injections of
      Abeta and a control (CKETIADGAC, scrambled) peptide injected into the
      contralateral cortex. These data suggest that blocking the binding of Abeta to
      p75(NTR) may reduce neuronal loss in Alzheimer's disease.

PMID- 18807175
TI  - A pilot study on the effects of heart rate variability biofeedback in patients
      with depression and in healthy subjects.
AB  - Decreased vagal activity and increased sympathetic arousal have been proposed as
      major contributors to the increased risk of cardiovascular mortality in patients
      with depression. It was aim of the present study to assess the feasibility of
      using heart rate variability (HRV) biofeedback to treat moderate to severe
      depression. This was an open-label study in which 14 patients with different
      degrees of depression (13 f, 1 m) aged 30 years (18-47; median; range) and 12
      healthy volunteers attended 6 sessions of HRV biofeedback over two weeks. Another
      12 healthy subjects were observed under an active control condition. At follow up
      BDI was found significantly decreased (BDI 6; 2-20; median 25%-75% quartile) as
      compared to baseline conditions (BDI 22;15-29) in patients with depression. In
      addition, depressed patients had reduced anxiety, decreased heart rate and
      increased HRV after conduction of biofeedback (p < 0.05). By contrast, no changes
      were noted in healthy subjects receiving biofeedback nor in normal controls. In
      conclusion, HRV biofeedback appears to be a useful adjunct for the treatment of
      depression, associated with increases in HRV.

PMID- 18807176
TI  - A proposed set of ethical practice guidelines in the assessment and treatment of
      pelvic floor disorders.
AB  - The treatment of pelvic floor disorders using biofeedback, behavioral therapies,
      and other applied psychophysiological treatments has been well documented as
      effective. Practitioners must take due care to ensure that they practice within
      the boundaries of what is common practice for their discipline and within the
      scope of practice allowed by their professional license as outlined by the
      appropriate state licensing law(s), the ethical principles and practice
      guidelines and standards for their discipline, and those of the Association of
      Applied Psychophysiology and Biofeedback if using a biofeedback assessment or
      treatment. Being competent to provide a particular treatment does not necessarily
      make it legal and/or ethical. This paper provides a set of recommended practice
      guidelines for use in the assessment and treatment of pelvic floor disorders.
      Please note that they have not at this time been endorsed as an official position
      of the Association of Applied Psychophysiology and Biofeedback or any other
      professional organization.

PMID- 18807178
TI  - Evaluating the performance of models for predicting the BRCA germline mutations
      in Han Chinese familial breast cancer patients.
AB  - PURPOSE: Established models (Penn, Myraid and BRCApro) are useful of estimating
      the probability that a person has a BRCA mutation. But the value of these models
      in Chinese population is unclear. The aim of the study is to evaluate the
      performance of three models on the assisting in pre-test genetic risk counseling.
      METHODS: Three risk assessment models, Penn II, Myriad and BRCApro, were applied
      to 212 familial breast cancer patients who had undergone BRCA1/2 mutation
      analysis. Sensitivity, specificity, positive and negative predictive values,
      likelihood ratios and area under the receiver operator characteristic (ROC) curve
      were calculated for each model. RESULTS: Myriad showed a better ROC curve than
      BRCApro either for BRCA1 or BRCA1/2 combination mutation prediction, but BRCApro
      had a higher positive likelihood ratio when using 10% as the probability
      threshold. The performance of three models improved when they were evaluated in
      66 patients from high risk families, presenting increased ROC and positive
      likelihood ratio. Especially that of BRCApro for BRCA2, the ROC was increased to
      0.716 and its positive likelihood was 5.6. CONCLUSION: Three models had the
      similar impact on the pre-test probability of BRCA mutation. But at a 10% cutoff
      point, BRCApro had the best BRCA mutation carrier prediction value. The
      performance of BRCApro for BRCA2 mutation prediction was improved when it was
      restricted in patients from high risk families.

PMID- 18807177
TI  - Post-transcriptional regulation of chemokine receptor CXCR4 by estrogen in HER2
      overexpressing, estrogen receptor-positive breast cancer cells.
AB  - Expression of the chemokine receptor CXCR4, a G protein-coupled receptor, and
      HER2, a receptor tyrosine kinase, strongly correlates with the aggressive and
      metastatic potential of breast cancer cells. We studied estrogen regulation of
      CXCR4 in estrogen receptor (ER)-positive MCF-7 breast cancer cells overexpressing
      HER2 (MCF7-HER2). Although estrogen evoked no change in CXCR4 mRNA levels, CXCR4
      protein was significantly up-regulated after estrogen treatment of these cells,
      whereas estrogen had no effect on CXCR4 protein level in parental MCF7 cells that
      are low in HER2. Use of the CXCR4 specific inhibitor, AMD 3100, indicated that
      this increase in CXCR4 protein was partially responsible for the increase in
      estrogen-induced migration of these cells. The estrogen-induced increase in CXCR4
      protein in MCF-7-HER2 cells was abrogated by the antiestrogen ICI 182780 and by
      gefitinib (Iressa; a phospho-tyrosine kinase inhibitor), indicating an ER
      mediated effect and confirming involvement of receptor tyrosine kinases,
      respectively. Using specific pathway inhibitors, we show that the estrogen
      induced increase in CXCR4 involves PI3K/AKT, MAPK and mTOR pathways. PI3K/AKT and
      MAPK pathways are known to result in the phosphorylation and functional
      inactivation of tuberin (TSC2) of tuberous sclerosis complex thereby negating its
      inhibitory effects on mTOR, which in turn stimulates the translational machinery.
      Small interfering RNA (siRNA) mediated knockdown of tuberin elevated the level of
      CXCR4 protein in MCF7-HER2 cells and also nullified further estrogen up
      regulation of CXCR4. This study suggests a pivotal role of PI3 K, MAPK and mTOR
      pathways, via tuberin, in post-transcriptional control of CXCR4, initiated
      through estrogen-stimulated crosstalk between ER and HER2. Thus, post
      transcriptional regulation of CXCR4 by estrogens acting through ER via kinase
      pathways may play a critical role in determining the metastatic potential of
      breast cancer cells.

PMID- 18807179
TI  - Glycosylation of human fetal mucins: a similar repertoire of O-glycans along the
      intestinal tract.
AB  - Intestinal mucins are very high molecular weight glycoproteins secreted by goblet
      cells lining the crypt and the surface of the colonic mucosa. Profound
      alterations of mucin O-glycans are observed in diseases such as cancer and
      inflammation, modifying the function of the cell and its antigenic and adhesive
      properties. Based on immunohistochemical studies, certain cancer- and
      inflammation- associated glycans have been defined as oncofetal antigens.
      However, little or no chemical analysis has allowed the structural elucidation of
      O-glycans expressed on human fetal mucins. In this paper, mucins were isolated
      from different regions of the normal human intestine (ileum, right, transverse
      and left colon) of eight fetuses with A, B or O blood group. After alkaline
      borohydride treatment, the released oligosaccharides were investigated by nanoESI
      Q-TOF MS/MS (electrospray ionization quadrupole time-of-flight tandem mass
      spectrometry). More than 117 different glycans were identified, mainly based on
      core 2 structures. Some core 1, 3 and 4 oligosaccharides were also found. Most of
      the structures were acidic with NeuAc residues mainly alpha2-6 linked to the N
      acetylgalactosaminitol and sulphate residues 3-linked to galactose or 6-linked to
      GlcNAc. In contrast to adult human intestinal mucins, Sda/Cad determinants were
      not expressed on fetal mucin O-glycans and the presence of an acidic gradient
      along the intestinal tract was not observed. Similar patterns of glycosylation
      were found in each part of the intestine and the level of expression of the major
      oligosaccharides was in the same order of magnitude. This study could help
      determining new oncofetal antigens, which can be exploited for the diagnosis or
      the treatment of intestinal diseases.

PMID- 18807181
TI  - Mistrust of outreach workers and lack of confidence in available services among
      individuals who are chronically street homeless.
AB  - This qualitative study explored how individuals who are homeless perceive
      outreach practices and available services. Interviews were conducted with 24
      people who had been homeless for >/=1 year and who consistently resided on the
      streets of west midtown, Manhattan, New York. Reasons why these individuals
      refuse services include a pervasive mistrust of outreach workers and the agencies
      that employ them, as well as a prominent lack of confidence in available
      services. The findings suggest a need for an approach to outreach that
      incorporates giving individualized attention from outreach workers, using an
      empathetic listening approach, minimizing stereotyping, providing greater
      choices, and employing formerly homeless people as outreach workers.

PMID- 18807180
TI  - Obstructive sleep apnea: the new cardiovascular disease. Part I: Obstructive
      sleep apnea and the pathogenesis of vascular disease.
AB  - Obstructive sleep apnea (OSA) is increasingly recognized as a novel
      cardiovascular risk factor. OSA is implicated in the pathogenesis of
      hypertension, left ventricular dysfunction, coronary artery disease and stroke.
      OSA exerts its negative cardiovascular consequences through its unique pattern of
      intermittent hypoxia. Endothelial dysfunction, oxidative stress, and inflammation
      are all consequences of OSA directly linked to intermittent hypoxia and critical
      pathways in the pathogenesis of cardiovascular disease in patients with OSA. This
      review will discuss the known mechanisms of vascular dysfunction in patients with
      OSA and their implications for cardiovascular disease.

PMID- 18807182
TI  - Clinical intake of child and adolescent consumers in a rural community mental
      health center: does wait-time predict attendance?
AB  - This study examines the clinic variable of wait-time as a predictor of intake
      attendance in a rural community mental health center (CMHC) serving child and
      adolescent consumers. Data from 1,317 contacts seeking services for a child or
      adolescent (ages 2-17) were examined. In logistic regression analysis, wait-time
      between initial consumer contact and intake appointment was identified as a
      significant predictor of appointment attendance, even after accounting for
      consumer variables. The impact of wait-time on the likelihood of intake
      appointment attendance was not moderated by the urgency of consumer need.
      Findings elucidate the odds of intake attendance versus non-attendance associated
      with each day of wait-time and clarify the impact of this clinic variable on pre
      intake attrition above and beyond more often studied consumer variables. These
      results provide information that can assist rural CMHCs in assessing the costs
      and benefits of steps to reduce wait-time or its impact.

PMID- 18807183
TI  - Abdominal carcinomatosis attributed to metastatic breast carcinoma.
AB  - A 41-year-old female suffered from epigastralgia and intermittent constipation
      for 10 months, and abdominal fullness and intermittent pain for 6 months, before
      seeking help. Double contrast barium study of the colon showed multiple
      indentations on the sigmoid, ascending, and proximal transverse portions with
      tethered adjacent mucosal outline as well as the presence of ascites compatible
      with peritoneal carcinomatosis. Mediolateral oblique mammogram showed a
      speculated mass with some intratumoral microcalcifications in the upper
      retroareolar portion of the right breast. Due to the persistent abdominal
      complaints, laparotomy was done. Breast lump biopsy was done simultaneously. On
      opening abdominal cavity, massive yellowish ascites was noted. Diffuse small
      nodules over omentum and mesentery retraction were found. Bilateral ovarian
      masses were also noted. Right oophorectomy and omentectomy were performed.
      Histologic findings and results of immunohistochemical stains were consistent
      with diagnosis of primary breast cancer with metastasis to ovary and omentum.

PMID- 18807184
TI  - Endoscopic biliary drainage by 7 Fr or 10 Fr stent placement in patients with
      acute cholangitis.
AB  - BACKGROUND AND STUDY AIMS: Endoscopic biliary drainage is an established mode of
      treatment for acute cholangitis. We compared the safety and efficacy of 7 Fr and
      10 Fr stent placement for biliary drainage in patients with acute cholangitis.
      PATIENTS AND METHODS: We recruited 40 patients with severe cholangitis who
      required endoscopic biliary drainage. Patients were randomized to have either a 7
      Fr or a 10 Fr straight flap stent placement during endoscopy. Outcome measures
      included complications related to endoscopic retrograde cholangiopancreatography
      (ERCP) and clinical outcome. RESULTS: Of 40 patients, 20 were randomized to the 7
      Fr stent group and 20 to the 10 Fr stent group. All patients had biliary
      obstruction due to stones in the common bile duct. Indications for biliary
      drainage were: fever >100.4 degrees F (n = 27), hypotension (n = 6), peritonism
      (n = 10), impaired consciousness (n = 8), and failure to improve with
      conservative management (n = 13). Biliary drainage was achieved in all patients.
      Abdominal pain, fever, jaundice, hypotension, peritonism, and altered sensorium
      improved after a median period of 3 days in both groups. Leukocyte counts became
      normal after a median time of 4 days in the 7 Fr stent group and 6 days in the 10
      Fr stent group. There were no ERCP-related complications. There were no instances
      of occlusion or migration of stent. The success rates of biliary drainage in
      cholangitis were not affected by the size of stent used. CONCLUSIONS: Biliary
      drainage by 7 Fr stent or 10 Fr stent is equally safe and effective treatment for
      patients with severe cholangitis.

PMID- 18807185
TI  - The importance of hopelessness among university students seeking psychiatric
      counseling.
AB  - Hopelessness is a clinically important state relative to morbidity and suicide
      risk among university students. We examined its role in relation to presenting
      concerns, diagnosis, psychopharmacologic treatment and spiritual orientation
      among students seeking treatment at a university counseling center. The most
      commonly identified concern was anxiety, followed by stress and depression.
      Eighty-two percent were given a DSM IV diagnosis. Hopelessness was higher among
      students dually diagnosed with anxiety and depressive disorders and those who
      were started on psychiatric medication. Spirituality was inversely correlated
      with hopelessness and constitutes a personal characteristic warranting further
      investigation. The concerns bringing students to counseling, the rates of DSM IV
      diagnosis and the use of psychiatric medication suggest a preponderance of
      psychopathology over developmental or situational concerns that may be more
      prominent than has been noted in the counseling literature. In this regard,
      hopelessness appears to be an important feature even beyond its relationship to
      suicidality and merits attention and evaluation in student counseling.

PMID- 18807186
TI  - Pacific Islands families study: intimate partner violence and postnatal
      depression.
AB  - AIM: The present study examined the association between maternal intimate partner
      violence (IPV) and postnatal depression (PND) 6 weeks after giving birth. STUDY
      DESIGN: Data were gathered from the Pacific Islands Families Study. Mothers of a
      cohort of Pacific infants born in Auckland, New Zealand during 2000 were
      interviewed 6 weeks after giving birth. There were 1,085 mothers cohabiting in
      married or de-facto partnerships who completed measures of IPV and PND at the 6
      week assessment point. RESULTS: Women who were victims of physical violence were
      more likely to report postnatal depressive symptoms than those who were not
      (29.6% vs. 10.9%, OR: 3.44, 95% CI: 2.42, 4.97). The adjusted odds remained
      statistically significant (OR: 2.34, 95% CI: 1.52, 3.60). CONCLUSION: Findings
      suggest that being the victim of physical violence more than doubles the risk of
      PND. The results of the study may help to develop culturally appropriate social
      services and policies for Pacific women.

PMID- 18807187
TI  - Gender, acculturation and alcohol use among Latina/o adolescents: a multi-ethnic
      comparison.
AB  - This is the first study to examine the relationship between acculturation and
      alcohol use by gender and ethnicity using a nationally representative sample of
      Hispanic and non-Hispanic white adolescents. Specifically, we use data from the
      National Longitudinal Study of Adolescent Health (Add Health) to explore alcohol
      use and binge drinking for a sample that includes 6792 non-Hispanic whites, 910
      Mexican Americans, 290 Cuban Americans, and 336 Puerto Ricans. Bivariate results
      reveal significant gender differences in alcohol use among first generation
      Mexican American, first generation Puerto Rican, and second generation Cuban
      American adolescents. In addition, these results indicate binge drinking differs
      significantly by gender among first generation Mexican American, first generation
      Cuban American, third plus generation Puerto Rican, and third plus generation non
      Hispanic white adolescents. Multivariate logistic regression reveals that gender
      also moderates the effect of acculturation as well as ethnicity on alcohol use
      and abuse. Among both males and females, first generation immigrants are
      significantly less likely than third plus generation immigrants to use alcohol
      and binge drink while selective acculturation significantly reduces the odds of
      both behaviors. However, the effects of immigrant generation and selective
      acculturation on binge drinking are larger for females. Further, the trajectories
      that alcohol use and binge drinking follow with acculturation differ
      significantly by gender and ethnicity. These results reaffirm the need to further
      develop theoretical models and intervention strategies that are both gender
      specific and culturally-specific, targeting high risk groups in particular in
      these efforts.

PMID- 18807188
TI  - Relation of nitrite to structural and mechanical adaptation of arteries during
      postnatal development.
AB  - Mammalian arteries undergo rapid remodeling during postnatal growth and
      development. The high wall shear stress at birth is an important mediator of
      postnatal endothelial nitric oxide (NO) and consequently of growth and
      remodeling. The objective of this study was to quantify the NO production in
      relation to geometric and mechanical remodeling of aorta and pulmonary artery
      during postnatal development. Fifty-one C57BL/6 mice aged from 1 to 33 days were
      divided into 8 age groups for measurements of nitrite (NO(x)). Systematic
      measurements of NO(x) in each rings were made in the main pulmonary artery and
      primary branch as well as along the length of aorta using the combination of a
      diazo coupling method and high-performance liquid chromatography. The NO(x) data
      on the aorta were correlated with data on the geometry (diameter, wall thickness)
      and mechanical properties (stress, strain, elastic modulus) in the same strain of
      mice under the same conditions. Our findings show postnatal age and vessel size
      affects the NO production; i.e., the NO(x) decreased with age and diameter.
      Furthermore, there is a significant positive correlation between strain and NO(x)
      but negative correlation between both wall thickness and elastic modulus and
      NO(x) levels. These findings suggest an important interplay between NO(x) and
      geometric and mechanical remodeling during postnatal growth and development.

PMID- 18807189
TI  - Changes in gene expression of matrix constituents with respect to passage of
      ligament and tendon fibroblasts.
AB  - Trauma to the knee joint often results in injury to one or more supporting soft
      tissue structures, such as the medial collateral (MCL) and anterior cruciate
      (ACL) ligaments. Also, a portion of the patellar tendon (PT) is frequently used
      as a replacement graft for the ACL, resulting in a PT defect. The healing
      responses of these tissues are dramatically different and range from spontaneous
      healing to little or no healing. Studies have suggested that native cell behavior
      could be responsible for differences in healing potential. However, it is
      difficult to make comparisons as the reported results are based on different
      cellular passages which could have a dramatic effect on their potential to form
      healing tissues. Therefore, the objective of this study was to quantify the gene
      expression of collagen and other matrix constituents of fibroblasts from the MCL,
      ACL, and PT to document how they change with cell passage. We hypothesized that
      MCL fibroblasts would possess higher potential for matrix production through
      passages than ACL and PT cells because the MCL mounts a robust healing response
      unlike the ACL and PT. These differences in matrix expression would be dependent
      on passage because at earlier passages all cells would mostly be proliferating
      while at later passages they would tend to become senescent. Cells were isolated
      from the MCL, ACL, and PT of three rats and passaged a total of five times
      (Passage 1 to Passage 5). Using real time RT-PCR, expression of all genes of
      interest (Collagen Type I (ligament/tendon's main matrix constituent), Collagen
      Type III, Fibronectin, Metalloprotease-13 [MMP-13], and Tissue Inhibitor of
      Metallopreotease-1 [TIMP-1]) were quantitatively assessed. It was found that cell
      number for all three fibroblast types remained high from Passage 1 to Passage 5.
      There was a statistically significant increase in Collagen Type I of rat MCL
      fibroblasts throughout passage (p < 0.05). This was evident in the higher
      relative abundance (to GAPDH) at Passages 3 and 4 (14.5 +/- 2.2 fold and 15.3 +/-
      6.9 fold, respectively) than at Passage 1 (3.3 +/- 2.6 fold) (p < 0.05). On the
      other hand, Collagen Type I expression for ACL and PT fibroblasts were lower than
      that of MCL fibroblasts and remained at 2.5 +/- 2.0 fold and 1.7 +/- 0.8 fold,
      respectively. Interestingly, the gene expressions of Collagen Type III,
      Fibronectin, MMP-13, and TIMP-1 for MCL, ACL, and PT fibroblasts were all
      relatively constant throughout passage and were not significantly different from
      one another. The findings of this study indicate that passage does affect the
      Collagen Type I gene expression of rat MCL fibroblasts and further show that for
      in vitro ligament tissue engineering efforts, MCL fibroblasts have a more robust
      potential for ligament remodeling and repair due to the increase in collagen gene
      expression.

PMID- 18807190
TI  - MUlti-Dimensional Spline-Based Estimator (MUSE) for motion estimation: algorithm
      development and initial results.
AB  - Image registration and motion estimation play central roles in many fields,
      including RADAR, SONAR, light microscopy, and medical imaging. Because of its
      central significance, estimator accuracy, precision, and computational cost are
      of critical importance. We have previously presented a highly accurate, spline
      based time delay estimator that directly determines sub-sample time delay
      estimates from sampled data. The algorithm uses cubic splines to produce a
      continuous representation of a reference signal and then computes an analytical
      matching function between this reference and a delayed signal. The location of
      the minima of this function yields estimates of the time delay. In this paper we
      describe the MUlti-dimensional Spline-based Estimator (MUSE) that allows accurate
      and precise estimation of multi-dimensional displacements/strain components from
      multi-dimensional data sets. We describe the mathematical formulation for two-
      and three-dimensional motion/strain estimation and present simulation results to
      assess the intrinsic bias and standard deviation of this algorithm and compare it
      to currently available multi-dimensional estimators. In 1000 noise-free
      simulations of ultrasound data we found that 2D MUSE exhibits maximum bias of 2.6
      x 10(-4) samples in range and 2.2 x 10(-3) samples in azimuth (corresponding to
      4.8 and 297 nm, respectively). The maximum simulated standard deviation of
      estimates in both dimensions was comparable at roughly 2.8 x 10(-3) samples
      (corresponding to 54 nm axially and 378 nm laterally). These results are between
      two and three orders of magnitude better than currently used 2D tracking methods.
      Simulation of performance in 3D yielded similar results to those observed in 2D.
      We also present experimental results obtained using 2D MUSE on data acquired by
      an Ultrasonix Sonix RP imaging system with an L14-5/38 linear array transducer
      operating at 6.6 MHz. While our validation of the algorithm was performed using
      ultrasound data, MUSE is broadly applicable across imaging applications.

PMID- 18807191
TI  - Culture in the classroom: developing teacher proficiency in delivering a
      culturally-grounded prevention curriculum.
AB  - The authors describe the training model used to develop proficiency in teaching a
      culturally-grounded prevention curriculum. Teachers believed it vital to discuss
      substance use and considered culture and ethnicity central to students' lives,
      although few had experience teaching prevention curricula. Training effects were
      evaluated using three datasets. Analyses showed that training should emphasize
      teaching adult learners; encompass culture from many perspectives; address the
      teaching of prevention curricula, and emphasize fidelity as imperative. Trainers
      found the embedded focus on culture in keepin' it REAL essential to success.
      Teachers learned that a prevention curriculum can be instructionally engaging
      while theory-driven and academically rigorous.

PMID- 18807192
TI  - Teaching prevention on sensitive topics: key elements and pedagogical techniques.
AB  - This paper presents a set of topical and pedagogical considerations for
      instructors teaching material on sensitive topics with either the primary or
      secondary aim of addressing prevention. Prevention can be approached as an effort
      to create changes in an individual's attitudes/beliefs, knowledge, and behavior.
      Following this framework, classroom content that challenges students'
      perceptions, preconceived notions, and attitudes can be seen as preventive in
      nature. Preparing students to work through the same layers of complexity that
      thoroughly trained and experienced researchers and practitioners struggle with
      requires particular attention to the classroom environment.

PMID- 18807193
TI  - Two key strategies for teaching prevention: specialized course and infusion.
AB  - Prevention is taught only rarely in counseling and counseling psychology
      curricula. Failure to teach it suggests that graduates may be less likely to
      conduct prevention. In this article, we describe two key strategies for
      addressing this problem, where prevention is being taught through (a) required
      courses, and (b) infusion within existing courses. Four training programs, two
      examples of each mode, are presented from the University of Cincinnati,
      Pennsylvania State University, Boston College, and the University of Minnesota.
      We describe the processes involved in developing and implementing these key
      pedagogical strategies that lead, we intend, to broadened application.

PMID- 18807194
TI  - Examining linguistic relativity hypothesis as one of the main views on the
      relationship between language and thought.
AB  - One of those features that set human societies apart from animal societies is the
      use of language. Language is a vital part of every human culture and is a
      powerful social tool that we master at an early age. A second feature of humans
      is our ability to solve complex problems. For centuries philosophers have
      questioned whether these two abilities are related and, if so, what the nature of
      the relationship between language and thought is. At the beginning of the last
      century psychologists joined this debate and it is a topic that is currently
      generating a lot of research. Another factor in the study of language and thought
      is the role of culture. When we study a language from another country we see that
      it is not just the words and grammar that are different but the customs and
      traditions as well. Even the ideas of that culture and the way of dealing with
      life can be different. There are a number of views on the nature of the
      relationship between language and thought. But here we are going to explore one
      of those views, the linguistic relativity hypothesis (LRH), concerning that the
      language a speaker uses influences the way the speaker thinks.

PMID- 18807195
TI  - Rottlerin induces pro-apoptotic endoplasmic reticulum stress through the protein
      kinase C-delta-independent pathway in human colon cancer cells.
AB  - Rottlerin, a compound reported to be a PKC delta-selective inhibitor, has been
      shown to induce growth arrest or apoptosis of human cancer cell lines. In our
      study, rottlerin dose-dependently induced apoptotic cell death in colon carcinoma
      cells. Treatment of HT29 human colon carcinoma cells with rottlerin was found to
      induce a number of signature ER stress markers; phosphorylation of eukaryotic
      initiation factor-2alpha (eIF-2alpha), ER stress-specific XBP1 splicing, and up
      regulation of glucose-regulated protein (GRP)-78 and CCAAT/enhancer-binding
      protein-homologous protein (CHOP). However, suppression of PKC delta expression
      by siRNA or overexpression of WT-PKC delta and DN-PKC delta did not abrogate the
      rottlerin-mediated induction of CHOP. These results suggest that rottlerin
      induces up-regulation of CHOP via PKC delta-independent pathway. Furthermore,
      down-regulation of CHOP expression using CHOP siRNA attenuated rottlerin-induced
      apoptosis. Taken together, the present study thus provides strong evidence to
      support an important role of ER stress response in mediating the rottlerin
      induced apoptosis.

PMID- 18807196
TI  - Recursive estimation of transient inhomogeneous zeta potential in microchannel
      turns using velocity measurements.
AB  - In the various biomedical microfluidic devices the target biomolecules are
      delivered by activating electroosmotic flows. The zeta potential of a
      microchannel wall, which determines the strength of the electroosmotic flow, is
      apt to change due to the adhesion of biomolecules such as DNA or protein
      especially around the microchannel turns. The resulting transient inhomogeneous
      profile of zeta potential alters flow pattern, volumetric flow rate and the band
      broading of solutes. In the present work, we have developed a method for the
      recursive estimation of transient inhomogeneous zeta potential in microchannel
      turns using velocity measurements. For the real time implementation of the
      present method, a compact and accurate reduced-order model is derived using the
      Karhunen-Loeve Galerkin method and the Helmholtz-Smoluchowski slip velocity. The
      present scheme of recursive estimation is an important prerequisite to the real
      time control of microfluidic devices.

PMID- 18807197
TI  - Cloning and characterization of CalS7 from Micromonospora echinospora sp.
      calichensis as a glucose-1-phosphate nucleotidyltransferase.
AB  - The deoxysugar biosynthetic gene cluster of calicheamicin contains the calS7,
      which encodes glucose-1-phosphate nucleotidyltransferase and converts glucose-1
      phosphate and nucleotides (NTP) to NDP-glucose and pyrophosphate. calS7 was
      expressed in Escherichia coli BL21(DE3), and the purified protein had significant
      thymidylyltransferase and uridylyltransferase activities as well, with some
      guanidylyltransferase activity but negligible cytidyl and adenyltransferase
      activity. The functions of thymidylyltransferase and uridylyltransferase were
      also verified using one-pot enzymatic synthesis of TMK and ACK. The products were
      analyzed by HPLC and ESI/MS, which showed peaks at m/z = 563 and 565 for TDP-D: 
      glucose and UDP-D-glucose, respectively, in negative mode.

PMID- 18807198
TI  - Conformational signatures of 13C chemical shifts in RNA ribose.
AB  - The conformational dependence of (13)C chemical shift values of RNA riboses
      determined by liquid-state NMR spectroscopy was evaluated using data deposited
      for RNA structures in the RCSD and BMRB data bases. Results derived support the
      applicability of the canonical coordinates approach of Rossi and Harbison (J Magn
      Reson 151:1-8, 2001) in liquid-state NMR to assess the sugar pucker of ribose
      units in RNA.

PMID- 18807200
TI  - Coordinate action of exiguobacterial oxidoreductive enzymes in biodegradation of
      reactive yellow 84A dye.
AB  - A novel bacterial species identified as Exiguobacterium sp. RD3 degraded the
      diazo dye reactive yellow 84A (50 mg l(-1)) within 48 h at static condition, at
      30 degrees C and pH 7. Lower salinity conditions were found to be favorable for
      growth and decolorization. Enzymatic activities of an H(2)O(2) independent
      oxidase along with laccase and an azoreductase suggest their prominent role
      during the decolorization of reactive yellow 84A. Presence of an H(2)O(2)
      independent oxidase in Exiguobacterium sp. RD3 was confirmed and hydrogen
      peroxide produced was detected by a coupled iodometric assay. Azoreductase
      activity was prominent in presence of cofactors NADH and NADP in mineral salt
      medium. Considerable depletion of COD of the dye solution during degradation of
      dye was indicative of conversion of complex dye into simple oxidizable products.
      Products of degradation were analyzed by HPLC, FTIR and GCMS. A possible product
      of the degradation was identified by GCMS. Degradation of dye resulted with
      significant reduction of phytotoxicity, confirming the environmentally safe
      nature of the degradation metabolites.

PMID- 18807199
TI  - Hormone interactions at the root apical meristem.
AB  - Plants exhibit an amazing developmental flexibility. Plant embryogenesis results
      in the establishment of a simple apical-basal axis represented by apical shoot
      and basal root meristems. Later, during postembryonic growth, shaping of the
      plant body continues by the formation and activation of numerous adjacent
      meristems that give rise to lateral shoot branches, leaves, flowers, or lateral
      roots. This developmental plasticity reflects an important feature of the plant's
      life strategy based on the rapid reaction to different environmental stimuli,
      such as temperature fluctuations, availability of nutrients, light or water and
      response resulting in modulation of developmental programs. Plant hormones are
      important endogenous factors for the integration of these environmental inputs
      and regulation of plant development. After a period of studies focused primarily
      on single hormonal pathways that enabled us to understand the hormone perception
      and signal transduction mechanisms, it became obvious that the developmental
      output mediated by a single hormonal pathway is largely modified through a whole
      network of interactions with other hormonal pathways. In this review, we will
      summarize recent knowledge on hormonal networks that regulate the development and
      growth of root with focus on the hormonal interactions that shape the root apical
      meristem.

PMID- 18807201
TI  - Income and recurrent events after a coronary event in women.
AB  - Strong evidence supports the existence of a social gradient in poor prognosis in
      patients with coronary heart disease (CHD). However, knowledge regarding what
      factors may explain this relationship is limited. We aimed to analyze in women
      CHD patients the association between personal income and recurrent events and to
      determine whether lifestyle, biological and psychosocial factors contribute to
      the explanation of this relationship. Altogether 188 women hospitalized for a
      cardiac event were assessed for personal income, demographic factors, lipids,
      inflammatory markers, cortisol, creatinine, lifestyle and psychosocial factors,
      i.e. alcohol consumption, smoking habits, body-mass index, depressive symptoms,
      anxiety, vital exhaustion, availability of social interaction, hostility and
      anger-related characteristics and were followed for cardiovascular death and
      recurrent acute myocardial infarction (AMI). During the 6-year follow-up 18
      patients deceased and 31 experienced cardiovascular death or non-fatal AMI. After
      adjustment for confounders, patients with medium and high income had lower risk
      for recurrent events relative to those with low income (HR (95% CI): 0.38 (0.15
      0.97) and 0.39 (0.17-0.93), respectively). Controlling for smoking reduced by
      12.8% the risk for recurrent events associated with high versus low income, while
      adjusting for depression decreased the risk for middle versus low income by
      13.5%. Anger symptoms explained 16.7% of the risk for recurrent events associated
      with middle versus low income and 10.2% of the risk for high versus low income.
      We suggest that in women with CHD low income is associated with recurrent events
      and that smoking, depressive symptomatology and anger symptoms may contribute to
      the explanation of this relationship.

PMID- 18807202
TI  - Larval aquatic and terrestrial mites infesting a temperate assemblage of
      mosquitoes.
AB  - We collected 22,769 adult female mosquitoes, representing 27 species, from light
      traps in Norfolk, Virginia (2006-2007) and examined them to assess infestation by
      larval mites. Mosquitoes were parasitized by two species of aquatic (Acari:
      Arrenuridae: Arrenurus) and three species of terrestrial mites (Acari:
      Erythraeidae). The prevalence of infestation varied from 0.55% (2006) to 0.17%
      (2007). The mean intensity of parasitism ranged from 3.6 mites per host (2006) to
      1.8 mites per host (2007). The most common host species for aquatic mites was
      Culex erraticus, while the most common host for terrestrial mites was Anopheles
      quadrimaculatus. Relationships between biotic and abiotic factors were
      investigated in an attempt to provide insight into temporal, spatial, and
      interspecific variation in mite-mosquito interactions. Scanning electron
      microscopy was used to examine the mode of attachment for larval mites. While the
      prevalence of aquatic mite parasitism was correlated for Culex erraticus, the
      invasive mosquito, Aedes albopictus, was never parasitized through the duration
      of the study.

PMID- 18807203
TI  - Resistance to the two-spotted spider mite (Tetranychus urticae) by acylsucroses
      of wild tomato (Solanum pimpinellifolium) trichomes studied in a recombinant
      inbred line population.
AB  - Trichome-based host plant resistance is a complex mechanism that could be used in
      tomato breeding to control arthropod pests. The aims of this work were to
      evaluate the plant traits (density of trichomes and acylsucrose production) and
      the functional relationships of these traits with mortality, repellence, and
      oviposition of Tetranychus urticae Koch (Acari: Tetranychidae). We used a
      population of recombinant inbred lines (RILs) derived from the cross between the
      wild tomato, Solanum pimpinellifolium L. 'TO-937', and the cultivated tomato,
      Solanum lycopersicum L. Multiple regression analyses showed that high acylsucrose
      content and high type-IV trichome density increased mortality and repellence, and
      reduced oviposition of T. urticae. Single regression analyses showed that a
      logistic model best explained the relationship between mortality or repellence
      and acylsucrose content, whereas a negative-exponential model best described the
      relationship between oviposition and acylsucrose content. Linear models were the
      best-fits for the three resistance variables with trichome IV density. Probit
      analysis was used to estimate acylsucrose effective doses, and revealed that 31
      and 10% of the RILs produced acylsucrose above the effective doses for 90%
      mortality or repellence, respectively. Altogether, these results indicate that S.
      pimpinellifolium may be a suitable genetic source of resistance to spider mites
      to be used in cultivated tomato.

PMID- 18807204
TI  - Aromatase (P450arom) and 11beta-hydroxylase (P45011beta) genes are differentially
      expressed during the sex change process of the protogynous rice field eel,
      Monopterus albus.
AB  - Steroids are known to play a crucial role in gonadal sex differentiation in many
      non-mammalian vertebrates, but also in the gonadal sex change of hermaphroditic
      teleosts. We investigated the expression of two genes encoding key steroidogenic
      enzymes, i.e., cytochrome P450 aromatase (P450arom) and cytochrome P45011beta
      hydroxylase (P45011beta), during the sex change of the protogynous rice field
      eel, Monopterus albus. Using RT-PCR with degenerate primers, we cloned rice field
      eel homologous fragments for both genes (rcP450arom and rcP45011beta) as
      indicated by the high level of homology with P450arom and P45011beta sequences
      from various vertebrates. Gonadal expression of rcP450arom and rcP45011beta mRNA
      levels were then assessed during the sex change by semi-quantitative RT-PCR and a
      real-time RT-PCR. rcP450arom was predominantly expressed in ovary, much less in
      ovotestis, and barely in testis. Conversely, P45011beta was markedly up-regulated
      at the onset of testicular development. These findings underline that regulation
      of steroidogenesis is an important process in the sex change of protogynous rice
      field eel, and they clearly indicate that the concomitant down-regulation of
      P450arom and up-regulation of P45011beta are of pivotal importance to the sex
      change of this species.

PMID- 18807205
TI  - Prediction of some important physical properties of sulfur compounds using
      quantitative structure-properties relationships.
AB  - In this work, physical properties of sulfur compounds (critical temperature (Tc),
      critical pressure (Pc), and Pitzer's acentric factor (omega)) are predicted using
      quantitative structure-property relationship technique. Sulfur compounds present
      in petroleum cuts are considered environmental hazards. Genetic algorithm based
      multivariate linear regression (GA-MLR) is used to select most statistically
      effective molecular descriptors on the properties. Using the selected molecular
      descriptors, feed forward neural networks (FFNNs) are applied to develop some
      molecular-based models to predict the properties. The presented models are quite
      accurate and can be used to predict the properties of sulfur compounds.

PMID- 18807206
TI  - Aliskiren: a rapidly, expanding role in the management of recalcitrant
      hypertension and renal disease.

PMID- 18807207
TI  - Renal resistive index and nocturnal non-dipping: is there an association in
      essential hypertension?
AB  - Renal Doppler ultrasonography (RDU) is a useful method to determine renal
      resistive index (RRI). The RRI has been used to evaluate target organ damage
      (TOD) in essential hypertension. Nocturnal non-dipping of blood pressure (BP) in
      essential hypertension was also associated with TOD. The relationship between
      increased RRI and non-dipping has not been specifically studied before. Patients
      with newly diagnosed essential hypertension underwent 24-h ambulatory BP
      monitoring, biochemistry analysis, 24-h urine testing, and RDU. Totally, 198
      patients (137 women, 61 men, aged 53.8 +/- 11.4 years) were included. Sixty-two
      patients were non-dippers, and 56 patients had increased RRI. RRI was increased
      in 32.3% of non-dipper patients and in 26.5% of dipper patients (P = 0.402). The
      RRIs of dippers were lower than the RRIs of non-dippers (0.65 +/- 0.06 vs. 0.68
      +/- 0.07, P = 0.036). Multivariate logistic regression analysis of potential
      factors predicting increased RRI disclosed that advanced age (OR 1.090, CI 1.042
      1.140, P < 0.0001) and increased pulse pressure (OR 1.037, CI 1.012-1.062, P =
      0.004) were independently associated with increased RRI. In multivariate linear
      regression analysis, using the same independent variables, we found that square
      root-transformed RRI was independently associated with age (Beta + 0.366, P <
      0.0001) and pulse pressure (Beta + 0.222, P = 0.001). Increased RRI and nocturnal
      non-dipping are not independently associated with each other in newly diagnosed
      essential hypertensive patients. Possible different mechanisms, or the same
      mechanisms but with different activation levels, may be responsible for the
      increased RRI and non-dipping as discrete pathologies.

PMID- 18807208
TI  - Recovery of photoinactivated photosystem II in leaves: retardation due to
      restricted mobility of photosystem II in the thylakoid membrane.
AB  - The functionality of photosystem II (PS II) following high-light pre-treatment of
      leaf segments at a chilling temperature was monitored as F(v)/F(m), the ratio of
      variable to maximum chlorophyll fluorescence in the dark-adapted state and a
      measure of the optimal photochemical efficiency in PS II. Recovery of PS II
      functionality in low light (LL) and at a favourable temperature was retarded by
      (1) water stress and (2) growth in LL, in both spinach and Alocasia macrorrhiza
      L. In spinach leaf segments, water stress per se affected neither F(v)/F(m) nor
      the ability of the adenosine triphosphate (ATP) synthase to be activated by far
      red light for ATP synthesis, but it induced chloroplast shrinkage as observed in
      frozen and fractured samples by scanning electron microscopy. A common feature of
      water stress and growth of plants in LL is the enhanced anchoring of PS II
      complexes, either across the shrunken lumen in water-stress conditions or across
      the partition gap in larger grana due to growth in LL. We suggest that such
      enhanced anchoring restricts the mobility of PS II complexes in the thylakoid
      membrane system, and hence hinders the lateral migration of photoinactivated PS
      II reaction centres to the stroma-located ribosomes for repair.

PMID- 18807209
TI  - Mapping the eight-item Parkinson's Disease Questionnaire (PDQ-8) to the EQ-5D
      utility index.
AB  - OBJECTIVE: To develop a function for mapping the eight-item Parkinson's Disease
      Questionnaire (PDQ-8) to the EuroQol Group's EQ-5D utility index. METHODS: Data
      from two surveys of 324 patients with Parkinson's disease was divided into two
      groups. One was used to estimate the mapping functions by regression methods and
      the other was used to validate the mapping functions. RESULTS: A regression model
      with a non-linear trend explained 55% of the variation in EQ-5D utility values
      and had a mean absolute deviation (MAD) of 0.083. A regression model assuming a
      linear trend explained 52% of the variation and had an MAD of 0.085. In the
      validation sample, predicted values based on the aforementioned models
      respectively explained 42 and 44% of the variation in the observed EQ-5D utility
      values and both had MADs of about 0.1. The confidence intervals of the mean
      difference between these predicted values and the observed values totally fell
      within the pre-defined equivalence margin of 0.03 points. These predicted values
      were also similar to the observed EQ-5D utility values in terms of their
      association with clinical variables. CONCLUSION: At the group level, but not at
      the individual level, the mapping functions can accurately map the PDQ-8 outcomes
      to the EQ-5D utility index.

PMID- 18807210
TI  - The effects of prolonged deep freezing on the biomechanical properties of
      osteochondral allografts.
AB  - Musculo-skeletal allografts sterilized and deep frozen are among the most common
      human tissue to be preserved and utilized in modern medicine. The effects of a
      long deep freezing period on cortical bone has already been evaluated and found
      to be insignificant. However, there are no reports about the influences of a
      protracted deep freezing period on osteochondral allografts. One hundred
      osteochondral cylinders were taken from a fresh specimen and humeral heads of 1
      year, 2 years, 3 years and 4 year old bones. Twenty chips from each period, with
      a minimum of 3 chips per humeral head. Each was mechanically tested by 3 point
      compression. The fresh osteochondral allografts were significantly mechanically
      better than the deep frozen osteochondral allografts. There was no statistical
      significant time dependent difference between the deep frozen groups in relation
      to the freezing period. Therefore, we conclude that, from the mechanical point of
      view deep freezing of osteochondral allografts over a period of 4 years, is safe
      without further deterioration of the biomechanical properties of the
      osteochondral allografts.

PMID- 18807211
TI  - The impact of the International Atomic Energy Agency (IAEA) program on radiation
      and tissue banking in Uruguay: development of tissues quality control and quality
      management system in the National Multi-Tissue Bank of Uruguay.
AB  - BNOT was created and regulated in 1977 and started its operation in 1978
      according to the Decree No. 86/1977. By the Decree 248/005 is transformed in the
      National Institute of Donation and Transplantation of Cells, Tissues and Organs
      (Instituto Nacional de Donacion y Trasplante de Celulas, Tejidos y Organos-
      INDT). The organisation has been operating within the State University Medical
      School and the Public Health Secretary and it is the governmental organisation
      responsible for the regulation, policy and management of donation and
      transplantation in Uruguay. By the Decree 160/2006 is responsible for human cells
      and tissues regulation too. The participation of the INDT in the IAEA program
      facilitated the introduction of the radiation sterilisation technique for the
      first time in the country. The radiation sterilisation of tissues processed by
      INDT (ex BNOT), was initially carried out in the 60 Cobalt Industrial Plant in
      the National Atomic Energy Commission of Argentina and now is carried out in
      INDT, using a Gamma Cell 220 Excel, which was provided by the IAEA through the
      national project URU/7/005. The results of the implementation of tissues, quality
      control and quality management system, are showed.

PMID- 18807212
TI  - Serum levels of angiogenic factors and their prognostic relevance in bladder
      cancer.
AB  - Angiogenesis plays a critical role in tumor growth. VEGF, angiopoietins (Ang-1,
      Ang-2) and their tyrosine kinase receptor Tie2 are major regulators of
      angiogenesis. The aim of this study was to evaluate the prognostic value of the
      serum levels of these factors in bladder cancer. We analyzed the serum samples of
      117 bladder cancer patients and 64 healthy volunteers by enzyme linked
      immunosorbent assay (ELISA) for Ang-1, Ang-2, VEGF and the extracellular domain
      of Tie2. The statistical evaluation of the obtained data was performed via Kaplan
      Meier log-rank test, univariate Cox analyses as well as Cox proportional hazards
      regression model. Serum Ang-1 levels of bladder cancer patients were
      significantly higher (p < 0.001), while soluble Ang-2 and Tie2 levels were
      significantly lower (p = 0.016 and p = 0.001 respectively) in patients than those
      in controls. Cox univariate analysis revealed high sTie2 serum level as a risk
      factor for metastasis and as a borderline significant risk factor for disease
      related death (p = 0.022 and p = 0.081 respectively). These correlations were
      independent from tumor stage and grade in a Cox multivariate model (p = 0.016 and
      p = 0.069). These data indicate that the serum levels of analyzed angiogenic
      factors do change characteristically in bladder cancer. The soluble extracellular
      serum level of Tie2 may provide a stage and grade independent diagnostic tool to
      select a high risk group of bladder cancer patients.

PMID- 18807213
TI  - The efficient generation of immunocompetent dendritic cells from leukemic blasts
      in acute myeloid leukemia: a local experience.
AB  - Dendritic cells (DCs) are the most important antigen presenting cells with
      potentially useful applications in cancer immunotherapy. Leukemic cells of
      patients with acute myeloid leukemia (AML) could be differentiated to DC-like
      cells possessing the ability of stimulating anti-leukemic immune response.
      Despite obvious progress in DC-based immunotherapy, some discrepancies were
      reported in differentiation potential of AML blasts from all patients toward DC
      like cells. The present study, as a local experience, was set up to generate DCs
      from AML blasts of various subtypes. Leukemic Blasts from 16 Iranian AML patients
      were differentiated into functional DCs by culturing in the presence of rhGM-CSF,
      rhIL-4 and TNF-alpha for 8 days. The morphology, expression of key surface
      molecules and allostimulatory activity of resultant DCs were compared with
      primary blasts and cultured but cytokine untreated control groups. The pattern of
      angiotensin-converting enzyme (ACE) expression was used to approve the leukemic
      origin of generated DCs. Neo-expression or upregulation of DC-associated markers
      were occurred during culturing period in cytokine treated cells compared with
      primary blasts and cultured but cytokine untreated control groups: CD1a (63.22%
      vs. 3.22% and 11.79%), CD83 (41.27% vs. 0.11% and 0.70%), CD40 (15.17% vs. 0.00%
      and 0.04%), CD80 (49.96 vs. 0.02% and 0.32%), CD86 (56.49% vs. 0.50% and 5.71%)
      and HLA-DR (52.52% vs. 14.32% and 2.49%) respectively. The potency of generated
      DCs to induce allogeneic T cell proliferation increased significantly compared to
      pre and post culture control groups (27,533.4 +/- 2,548.3, 8,820.4 +/- 1,639.4
      and 3,200.35 +/- 976 respectively). The expression pattern of ACE in AML-DCs,
      blast cells and DCs derived from normal monocytes (7.93%, 1.28% and 74.97%
      respectively) confirmed the leukemic origin of DCs. Our data confirmed the
      generation of sufficient AML-derived cells with the properties of DCs in all
      cases. This potency of AML blasts, offers a useful route for active immunotherapy
      of AML patients.

PMID- 18807214
TI  - Yarrowia lipolytica growth under increased air pressure: influence on enzyme
      production.
AB  - Improvement of microbial cell cultures oxygenation can be achieved by the
      increase of total air pressure, which increases oxygen solubility in the medium.
      In this work, a pressurized bioreactor was used for Yarrowia lipolytica batch
      cultivation under increased air pressure from 1 to 6 bar. Cell growth was
      strongly enhanced by the pressure rise. Fivefold and 3.4-fold increases in the
      biomass production and in specific growth rate, respectively, were observed under
      6 bar. The increase of oxygen availability caused the induction of the
      antioxidant enzyme superoxide dismutase, which indicates that the defensive
      mechanisms of the cells against oxidative stress were effective and cells could
      cope with increased pressure. The pregrowth of Y. lipolytica under increased
      pressure conditions did not affect the lipase production ability of the cells.
      Moreover, the extracellular lipase activity increased 96% using a 5-bar air
      pressure instead of air at 1-bar pressure during the enzyme production phase.
      Thus, air pressure increase in bioreactors is an effective mean of cell mass and
      enzyme productivity enhancement in bioprocess based in Y. lipolytica cultures.

PMID- 18807215
TI  - Validation of a new coma scale, the FOUR score, in the emergency department.
AB  - OBJECTIVE: Full Outline of Unresponsiveness (FOUR) score has previously been
      validated scale in the Neurosciences Intensive Care Unit. In this study, we
      sought to validate the use of FOUR score in the emergency department (ED) using
      non-neurology staff. We also compared its performance to the Glasgow Coma Scale
      (GCS) and correlated it to functional outcome at hospital discharge and overall
      survival. METHODS: We prospectively rated 69 patients with initial neurologic
      symptoms presenting to the ED. Three types of examiners performed the FOUR score:
      ED physician, ED resident, and ED nurse. Patients were followed through hospital
      discharge; functional outcome was measured using modified Rankin Score (mRS).
      RESULTS: Interrater reliability for FOUR score and GCS was excellent
      (respectively, kappa(w) = 0.88 and 0.86). Both FOUR score and GCS predicted
      functional outcome, and overall survival with and without adjustment for age,
      sex, and alertness group. CONCLUSION: The FOUR score can be reliably used in the
      ED by non-neurology staff. Both FOUR score and GCS performed equally well, but
      the neurologic detail incorporated in the FOUR score makes it more useful in
      management and triage of patients.

PMID- 18807216
TI  - Dopamine D2-receptor-mediated increase in vascular and endothelial NOS activity
      ameliorates cerebral vasospasm after subarachnoid hemorrhage in vitro.
AB  - INTRODUCTION: Cerebral vasospasm after subarachnoid hemorrhage (SAH) is a serious
      complication resulting in delayed neurological deficit, increased morbidity,
      mortality, longer hospital stays, and rehabilitation time. It afflicts
      approximately 35 per 100,000 Americans per year, and there is currently no
      effective therapy. We present in vitro data suggesting that increasing intrinsic
      nitric oxide relaxation pathways in vascular smooth muscle via dopaminergic
      agonism ameliorates cerebral vasospasm after SAH. METHODS: Cerebrospinal fluid
      (CSF) from patients with cerebral vasospasm after SAH (CSF(V)) was used to induce
      vasospasm in porcine carotid artery in vitro. Dopamine was added to test its
      ability to reverse spasm, and specific dopamine receptor antagonists were used to
      determine which receptor mediated the protection. Immunohistochemical techniques
      confirmed the presence of dopamine receptor subtypes and the involvement of NOS
      in the mechanism of dopamine protection. RESULTS: Dopamine receptor 1, 2, and 3
      subtypes are all present in porcine carotid artery. Dopamine significantly
      reversed spasm in vitro (67% relaxation), and this relaxation was prevented by
      Haloperidol, a D(2)R antagonist (10% relaxation, P < 0.05), but not by D(1) or
      D(3)-receptor antagonism. Both eNOS and iNOS expression were increased
      significantly in response to CSF(V) alone, and this was significantly enhanced by
      addition of dopamine, and blocked by Haloperidol. CONCLUSION: Cerebral vasospasm
      is significantly reversed in a functional measure of vasospasm in vitro by
      dopamine, via a D(2)R-mediated pathway. The increase in NOS protein seen in both
      the endothelium and vascular smooth muscle in response to CSF(V) is enhanced by
      dopamine, also in a D(2)R-dependent mechanism.

PMID- 18807217
TI  - The utility of conductive plastic electrodes in prolonged ICU EEG monitoring.
AB  - We investigated the feasibility and utilization of conductive plastic electrodes
      (CPEs) in patients undergoing continuous video-electroencephalographic (EEG)
      monitoring in the intensive care unit (ICU), and assessed the quality of brain
      magnetic resonance imaging (MRI) and computed tomography (CT) images obtained
      during this period. A total of 54 patients were monitored. Seizures were recorded
      in 16 patients. Twenty-five patients had neuroimaging performed with electrodes
      in place; 15 MRI and 23 CT scans were performed. All patients had excellent
      quality anatomical images without clinically significant artifacts, and without
      any signs or symptoms that raised safety concerns. Recording quality of the EEG
      was indistinguishable to that achieved with standard gold electrodes. The use of
      CPEs allowed for uninterrupted EEG recording of patients who required urgent
      neuroimaging, and decreased the amount of time spent by the technologists
      required to remove and reattach leads.

PMID- 18807218
TI  - Near-infrared spectroscopy can monitor dynamic cerebral autoregulation in adults.
AB  - OBJECTIVE: To study the correlation between a dynamic index of cerebral
      autoregulation assessed with blood flow velocity (FV) using transcranial Doppler,
      and a tissue oxygenation index (TOI) recorded with near-infrared spectroscopy
      (NIRS). METHODS: Twenty-three patients with sepsis, severe sepsis, or septic
      shock were monitored daily on up to four consecutive days. FV, TOI, and mean
      arterial blood pressure (ABP) were recorded for 60 min every day. An index of
      autoregulation (Mx) was calculated as the moving correlation coefficient between
      10-s averaged values of FV and ABP over moving 5 min time-windows. The index Tox
      was evaluated as the correlation coefficient between TOI and ABP in the same way.
      The indices Mx and Tox, ABP and arterial partial pressure of CO(2) were averaged
      for each patient. RESULTS: Synchronized slow waves, presenting with periods from
      20 s to 2 min, were seen in the TOI and FV of most patients, with a reasonable
      coherence between the signals in this bandwidth (coherence >0.5). The indices, Mx
      and Tox, demonstrated good correlation with each other (R = 0.81; P < 0.0001) in
      the whole group of patients. Both indices showed a significant (P < 0.05)
      tendency to indicate weaker autoregulation in the state of vasodilatation
      associated with greater values of arterial partial pressure of CO(2) or lower
      values of ABP. CONCLUSION: NIRS shows promise for the continuous assessment of
      cerebral autoregulation in adults.

PMID- 18807219
TI  - Posttraumatic vasospasm detected by continuous brain tissue oxygen monitoring:
      treatment with intraarterial verapamil and balloon angioplasty.
AB  - INTRODUCTION: Posttraumatic vasospasm (PTV) is a relatively common event
      following traumatic brain injury (TBI) that has been strongly correlated with
      worse neurological outcome in many studies. However, vasospasm continues to be an
      under-recognized source of secondary injury following TBI, and currently
      published guidelines do not address screening or management strategies for PTV.
      Brain tissue oxygen (P(bt)O(2)) monitoring probes allow for continuous screening
      for cerebral hypoxia following TBI, but their use as a monitor for PTV has not
      been previously described. METHODS: Case report and literature review. RESULTS:
      We present a case of PTV identified by persistent low P(bt)O(2) despite
      aggressive medical therapy. Computed tomography and digital subtraction
      angiography confirmed severe cerebral arterial vasospasm involving both anterior
      and posterior circulations. The patient was successfully treated with serial
      intraarterial therapy including balloon angioplasty and verapamil infusion.
      CONCLUSION: Posttraumatic vasospasm should be included in the differential
      diagnosis of cerebral hypoxia (e.g., low P(bt)O(2)) following TBI. Management
      strategies for PTV may include early, aggressive intraarterial therapies
      including drug infusion and balloon angioplasty.

PMID- 18807220
TI  - Immunogenicity of a cholera toxin B subunit Porphyromonas gingivalis fimbrial
      antigen fusion protein expressed in E. coli.
AB  - The gram-negative anaerobic oral bacterium Porphyromonas gingivalis initiates
      periodontal disease through fimbrial attachment to saliva-coated oral surfaces.
      To study the effects of immunomodulation on enhancement of subunit vaccination,
      the expression in E. coli and immunogenicity of P. gingivalis fimbrial protein
      (FimA) linked to the C-terminus of the cholera toxin B subunit (CTB) were
      investigated. Complementary DNAs encoding the P. gingivalis 381 fimbrillin
      protein sequence FimA1 (amino acid residues 1-200) and FimA2 (amino acid residues
      201-337) were cloned into an E. coli expression vector downstream of a cDNA
      fragment encoding the immunostimulatory CTB. CTB-FimA1 and CTB-FimA2 fusion
      proteins synthesized in E. coli BL21 (DE3) cells were purified under denaturing
      conditions by Ni2+-NTA affinity column chromatography. Renaturation of the CTB
      FimA1 and CTB-FimA2 fusion proteins, permitted identification of CTB-FimA
      pentamers and restored CTB binding activity to GM1-ganglioside to provide a
      biologically active CTB-FimA fusion protein. Mice orally inoculated with purified
      CTB-FimA1 or CTB-FimA2 fusion proteins generated measurable FimA1 and FimA2 IgG
      antibody titers, while no serum fimbrial IgG antibodies were detected when mice
      were inoculated with FimA1 or FimA2 proteins alone. Immunoblot analysis confirmed
      that sera from mice immunized with CTB linked to FimA1 or FimA2 contained
      antibodies specific for P. gingivalis fimbrial proteins. In addition, mice
      immunized with FimA2 or CTB-FimA2 generated measurable intestinal IgA titers
      indicating the presence of fimbrial antibody class switching. Further, mice
      orally immunized with CTB-FimA1 generated higher IgA antibody titers than mice
      inoculated with FimA1 alone. The experimental data show that the
      immunostimulatory molecule CTB enhances B cell-mediated immunity against linked
      P. gingivalis FimA fusion proteins, in comparison to immunization with FimA
      protein alone. Thus, linkage of CTB to P. gingivalis fimbrial antigens can
      increase subunit vaccine immunogenicity to provide enhanced protection against
      periodontal disease.

PMID- 18807221
TI  - Genetic analysis of two porcine reproductive and respiratory syndrome viruses
      with different virulence isolated in China.
AB  - The S1 and SY0608 strains of porcine reproductive and respiratory syndrome virus
      (PRRSV) were individually isolated and had different pathogenicity in pigs in
      1997 and 2006. In order to understand their genomic characteristics, the full
      length genome of S1 and SY0608 isolates were sequenced and analyzed. The results
      indicated that their genome composition differed significantly and shared only
      88.5% nucleotide identity with each other. The genetic variation and amino acid
      substitutions were not randomly distributed in the genome, and mainly focused on
      ORF1a, ORF3 and ORF5. The SY0608 strain, with high pathogenicity, had a 30-amino
      acid deletion at amino acid positions 480 and 532-560 in comparison with the S1
      strain. The alignment of amino acid sequence of Nsp1-Nsp8, GP2-GP5, M and N of S1
      and SY0608 with other PRRSV isolates demonstrated that variation was mainly found
      in the Nsp2, GP3 and GP5 proteins. In comparison with the S1 strain, the SY0608
      strain showed some potential glycosylation site mutations in GP5 at amino acid
      positions between 26 and 39, which might be associated with viral antigenicity.
      Phylogenetic analysis showed that the two strains belonged to two different
      branches that do not indicate differences in pathogenicity. Interestingly, the
      deletion strains isolated recently in China formed a new minor branch, revealing
      the same evolutionary trend.

PMID- 18807222
TI  - Psychiatric disorders and symptom severity in referred versus non-referred
      overweight children and adolescents.
AB  - BACKGROUND: This study aimed firstly to investigate whether youngsters referred
      for overweight treatment differ from non-referred overweight youngsters on the
      prevalence of psychiatric disorders and psychological symptoms. Secondly, the
      potentially moderating role of age, gender, socio-economic status and degree of
      overweight in the association of referral status and mental disorder in
      overweight youth was explored. METHODS: Participants were 155 overweight
      youngsters enrolled in an obesity treatment programme (mean age = 13.76; mean BMI
      = 33.99) and 73 non-referred overweight youngsters (mean age = 13.74; mean BMI =
      27.35). The Structured Clinical Interview for DSM-IV-Childhood version and the
      Child version of the Eating Disorder Examination were administered and
      participants filled out the Children's Depression Inventory, the Spence
      Children's Anxiety Scale and the Youth Self Report. Parents were asked to
      complete the Child Behavior Checklist. RESULTS: In the referred group 37.50% and
      in the non-referred group 23.29% of the participants met criteria for at least
      one mental disorder. In both groups, anxiety disorders were most prominent.
      Overall, a higher prevalence of mental disorders was found in the referred group.
      Referred youth displayed significantly more 'full blown' eating disorders and
      binge eating than non-referred youngsters and exhibited a significantly greater
      severity of self- and parent-reported internalizing symptoms. Referral was also
      associated with a significantly higher degree of overweight and significantly
      lower SES. After controlling for these pre-existing differences in degree of
      overweight and SES, only the greater severity of parent-reported internalizing
      symptoms in referred youth remained significant. Older age was generally
      predictive for the presence of mental disorders and in the non-referred group SES
      was positively associated with psychiatric disorder. CONCLUSIONS: A substantial
      proportion of overweight youngsters suffer from mental disorders. Referral status
      and age are associated with the presence of psychopathology. However, differences
      between referred and non-referred youngsters are not as pronounced as expected on
      the basis of earlier research in the field.

PMID- 18807223
TI  - Adherence and psychopathology in children and adolescents with cystic fibrosis.
AB  - BACKGROUND: The striking increase in the lifespan of individuals with cystic
      fibrosis (CF) has largely been attributed to the dramatic improvements in
      treatment regimens. These treatments are time intensive and may interfere with
      healthy development and family function. The objective of this study was to
      investigate the association between psychopathology and treatment adherence in
      children and adolescents with CF. METHODS: Structured psychiatric interviews were
      performed on 52 patients with CF. Additional information on family function and
      youth behaviors were also collected. Youth and parent reports of adherence to the
      CF treatments were obtained and compared with the CF teams' records. RESULTS: The
      mean overall adherence to the CF teams' recommendations was 77-81% for the child
      and parent reports, respectively. Children with anxiety disorders and families
      who were more cohesive showed significantly higher rates of adherence to the CF
      treatments. In addition, children in families with a balance of structure and
      flexibility also report higher levels of adherence to the CF treatments.
      CONCLUSIONS: Anxiety disorders in children with CF may be associated with
      increased adherence to the numerous CF treatment regimens. In addition, family
      patterns that are cohesive and balanced are better able to incorporate the CF
      treatments into family life.

PMID- 18807224
TI  - Use of dynamic susceptibility-contrast MRI (DSC-MRI) to assess perfusion changes
      in the ipsilateral brain parenchyma from glioblastoma.
AB  - INTRODUCTION: We investigated the effect of increased tumor perfusion using
      dynamic susceptibility-contrast magnetic resonance imaging (DSC-MRI) in
      glioblastoma (GBM) patients on the surrounding ipsilateral brain tissue with
      respect to perfusion of the normal, unaffected contralateral brain and of the
      tumor. MATERIAL AND METHODS: DSC-MRI was performed in 11 patients with
      glioblastoma using a multislice T2*-weighed EPI sequence (TR/TE = 2,000/62 ms;
      FOV 240 mm; matrix 128 x 128; slice thickness 6 mm) on a standard clinical 1.5
      Tesla scanner during intravenous injection of 40 cc Gadolinium-DTPA at a flow
      rate of 5 cc/s. Maps for relative regional cerebral blood volume (rCBV) and
      relative regional cerebral blood flow (rCBF) were created and relative values
      analyzed in relation to the arterial input. RESULTS: Relative CBV and CBF were
      significantly higher in gray matter than in the respective white matter (paired t
      test; P < 0.001) with a high correlation for both perfusion parameters between
      the gray and the white matter in both ipsilateral and contralateral brain (P <
      0.001). The highest values for rCBV and rCBF were found in solid tumor tissue
      with a significant positive correlation between tumor and the adjacent gray
      matter (for both rCBV and rCBF; P < 0.001). CONCLUSION: In GBM patients there is
      increased metabolism and thus increased rCBV and rCBF within the tumor. This
      increased perfusion of the tumor is not at the expense of perfusion of the
      ipsilateral normal brain parenchyma and in fact, the rCBV and rCBF values are
      linked to tumor-induced changes in rCBV and rCBF.

PMID- 18807225
TI  - Antithrombotic therapy in atrial fibrillation: guidelines translated for the
      clinician.
AB  - Atrial fibrillation (AF) is the most common cardiac arrhythmia in clinical
      practice, accounting for approximately one-third of hospitalizations for cardiac
      rhythm disturbances. The highest incidence of AF is in patients 70-80 years old
      and other high-risk populations. Although the diagnosis of AF is usually
      straightforward, effective treatment strategies are less well implemented. This
      is particularly true for antithrombotic therapy, which is very effective at
      preventing thromboembolic complications of AF. Stroke is the most significant
      morbidity in AF patients. The yearly risk of stroke increases from 1.5% for AF
      patients aged 50-59 to 23% for those aged 80-89. Ischemic strokes secondary to AF
      carry twice the risk of death when compared with strokes from other causes. We
      provide a practical and useful review of the most recent American College of
      Cardiology/American Heart Association/European Society of Cardiology guidelines
      based care and future directions of antithrombotic therapy for patients with AF.

PMID- 18807226
TI  - Purification and properties of fluoroacetate dehalogenase from Pseudomonas
      fluorescens DSM 8341.
AB  - The degradation of fluoroacetate by microorganisms has been established for some
      time, although only a handful of dehalogenases capable of hydrolyzing the stable
      C-F bond have been studied. Pseudomonas fluorescens DSM 8341 was originally
      isolated from soil and readily degrades fluoroacetate, thus it was thought that
      its dehalogenase might have some desirable properties. The enzyme was purified
      from cell-free extracts and characterised: it is a monomer of 32,500 Da, with a
      pH optimum of 8 and is stable between pH 4 and 10; its activity is stimulated by
      some metal ions (Mg(2+), Mn(2+) and Fe(3+)), but inhibited by others (Hg(2+),
      Ag(2+)). The enzyme is specific for fluoroacetate, and the K(m) for this
      substrate (0.68 mM) is the lowest determined for enzymes of this type that have
      been investigated to date.

PMID- 18807227
TI  - Primary hepatic marginal zone B cell lymphoma of mucosa-associated lymphoid
      tissue type: case report and review of the literature.
AB  - A primary hepatic marginal zone B cell lymphoma of mucosa-associated lymphoid
      tissue (MALT) is very rare. We found a solitary mass 27 mm in size in the left
      lobe of the liver of a 58-year-old Japanese man with a history of hepatitis-C
      infection. Based on the results of imaging studies, the tumor was diagnosed as a
      hepatocellular carcinoma (HCC). The left lobe of the liver was lobectomized and
      microscopic findings showed that the tumor was a hepatic MALT lymphoma, while
      immunohistochemistry showed it to be positive for CD20 and CD79a. In a
      fluorodeoxyglucose-positron emission tomography examination integrated with
      computed tomography scanning (FDG-PET CT) before surgery, the tumor was revealed
      to have a high standardized uptake value (SUV) for FDG. The patient received
      chemotherapy after surgery. To the best of our knowledge, 45 cases had been
      reported with a mean age for all patients of 61.4 years. The pathogenesis remains
      unclear, although half of the patients had a past history of chronic inflammatory
      liver disease. Surgical resection was performed in most cases and some patients
      received postoperative chemotherapy or radiotherapy. The clinicopathologic
      characteristics and management of this extremely rare disease are also discussed.

PMID- 18807228
TI  - Coma caused by isoniazid poisoning in a patient treated with pyridoxine and
      hemodialysis.
AB  - Isoniazid is widely used to treat tuberculosis. In populations with a high
      prevalence rate of tuberculosis, acute ingestion of isoniazid has been reported
      as a potential cause of coma. In this study, we present the diagnosis and
      treatment of isoniazid poisoning in a case with acute coma as the major clinical
      presentation.A 32-year-old male who ingested 12 g isoniazid (2 hours prior to
      medical attention) was brought to the emergency department while in a coma and
      experiencing frequent seizures. Initial treatment with large doses of pyridoxine
      (for 6 hours) failed to awaken this patient. The patient was then given
      hemodialysis and pyridoxine; after 3 days he awoke from coma, with no further
      reported seizures.Isoniazid poisoning should be suspected in patients whose major
      symptoms are coma and seizure, especially those who have access to isoniazid.
      Monitoring the blood level of isoniazid will establish the diagnosis and help
      clinical management. A combination of hemodialysis and pyridoxine is effective in
      treating isoniazid poisoning.

PMID- 18807229
TI  - [Practice of recognizing benzene-caused occupational diseases in 2006].
AB  - BACKGROUND AND PURPOSE: Benzene-caused hematologic diseases can be recognized as
      occupational diseases (ODs) if they fulfill the legal requirements specified
      under No. 1303 of the appendix of the German ordinance on ODs. The aim of this
      study is to analyze the most important criteria that determined whether these
      diseases were recognized or rejected as ODs according to No. 1303 in 2006.
      METHODS: In 2006, 70 suspected cases of OD No. 1303 reported in North Rhine
      Westphalia were examined in terms of diagnosis, notifiers, cumulative benzene
      exposures, professions, coexposures, delays in notification, latency periods,
      interim periods, and recognition criteria. RESULTS: 70 benign and malignant
      diseases of myeloid and lymphoid origin were reported as suspected ODs, among
      them 41 B-cell non-Hodgkin's lymphomas (B-cell NHL). Latency periods ranged
      between 14 and 57 years (median 37; mean 36.3+/-11.4; n=45), estimated cumulative
      benzene exposures varied from 0 to 144 ppm-years (median 12; mean 11.4+/-22.8;
      n=59). Four of 70 suspected cases were recognized as OD No. 1303. In 37 cases
      (52.9%), the nature of the disease was assessed as being nontypical of OD No.
      1303, in 50 cases (71.4%), no sufficient benzene exposure could be found. Mature
      cell NHL and Hodgkin's lymphoma were not recognized as OD. Cumulative benzene
      exposures<or=12.3 ppm-years were not regarded as being sufficient to cause OD No.
      1303. CONCLUSION: When diagnosing hematologic diseases, physicians should ask the
      patients about their occupational history and, in particular, consider benzene
      exposures dating back several decades. To improve the state of knowledge of OD
      No. 1303, it is important that diseases are consistently classified according to
      WHO criteria and any kind of myeloid and lymphoid disease, including NHL, is
      reported.

PMID- 18807230
TI  - [Celiac sprue and malignancies: analysis of risks and prevention strategies].
AB  - Although the absolute risk of enteropathy-associated malignancies in celiac
      disease is generally very small due to low prevalence/incidence rates, the
      relative risk may be considerable so that prevention strategies based on
      appropriate data seem clinically desirable. The great majority of the case
      control and cohort studies which have been published in the last years point to a
      significantly elevated risk for tumors in the gastrointestinal (GI) tract in
      terms of hazard/odds ratios, observed/expected ratios, and/or standardized
      incidence/morbidity ratios in the magnitude>5.0, whereas the risk for tumor
      outside the GI tract seems to be much lower (PubMed December 2007). Chronic
      inflammation with persistent symptoms/complaints and especially chronic
      refractory disease type II are considered to be particular individual risk
      factors. In addition, genetic factors and/or certain gene combinations may
      unfavorably influence the course of the disease. In the absence of controlled and
      prospective trials and corresponding evidence-based guidelines as they have been
      published for colon cancer, the strategies of prevention in patients with celiac
      disease differ from center to center according to their own experience/
      expertise. Besides regular clinical, serologic/immunologic and
      endoscopic/histologic assessment a careful history taking with special regard to
      the disease course and a detailed ultrasound examination of the entire abdomen in
      patients at risk may play an important role in the long-term follow-up.

PMID- 18807231
TI  - [Tablet splitting: do discount contracts influence prescribing quality?].
AB  - BACKGROUND: In Germany, about one fourth of all tablets are split before
      ingestion. Since April 2007, by German law, pharmacists are legally obligated to
      substitute a prescribed drug for a generic drug, provided the patients' health
      insurance company has made corresponding contracts with pharmaceutical companies
      (discount contracts). However, generic drugs may differ substantially in their
      splitting properties. Until now it is unknown how generic substitutions due to
      discount contracts will influence the prescribing quality with regard to tablet
      splitting. METHODS: The prescription data of 425 ambulatory patients with
      polymedication insured at the Allgemeine Ortskrankenkasse (AOK) were analyzed and
      their drugs switched according to current discount contracts. RESULTS: Altogether
      24% of all tablets were split before ingestion. For 54% of these split tablets
      (182 of 335) existing discount contracts mandated generic substitution. In about
      10% of the substitutions there was a chance of substituting a scored tablet for a
      dosage form not suitable for splitting (unscored tablet or capsule). BACKGROUND:
      Therefore, current legislation should not only aim at reducing medication cost
      but also safeguard both effectiveness of the drugs and handling by the patients.

PMID- 18807232
TI  - [Thy thyroid nodule--differential diagnostics and treatment concepts].

PMID- 18807233
TI  - [Eosinophilia--a challenging differential diagnosis].
AB  - BACKGROUND: Eosinophilia is not uncommon in clinical practice. The main causes
      are allergies and parasitic infections. Rarely, eosinophilia is associated with
      pulmonary affections, malignant tumors, gastroenteritis, and autoimmune diseases.
      A new classification based on pathophysiological data for the hypereosinophilic
      syndrome in order to simplify diagnosis and therapy was introduced in 2006. CASE
      REPORT: A 22-year-old man was admitted to another hospital because of acute
      abdominal pain. An unspecific colitis was diagnosed. Blood counts showed a mild
      neutrophilic leukocytosis (12.6 Gpt/l) with a severe relative eosinophilia (30%),
      thrombocytopenia (67 Gpt/l), and an increased C-reactive protein (CRP 122 mg/l).
      The patient also had a deep venous thrombosis of the left leg. An explorative
      laparotomy was performed because of a strong suspicion of a presacral abscess.
      Pulmonary embolism and embolic pneumonia developed after surgery. A macular
      cockade exanthema on the trunk and extremities was found. Histological
      examination revealed perivascular eosinophilic infiltrates. Histological and
      cytological analysis of bone marrow showed many eosinophilic granulocytes and a
      hypercellular medulla without increased numbers of blasts. No parasites in the
      blood and stools were found, and there was no evidence of neoplasm or cardiac
      involvement. p- and c-ANCAs (antineutrophil cytoplasmic antibodies), ANAs
      (antinuclear antibodies), and antibody against dsDNA were negative. Further
      genetic, FISH (fluorescence in situ hybridization), and PCR (polymerase chain
      reaction) analyses showed no evidence for chromosomal aberrations. An undefined
      hypereosinophilic syndrome with multiple organ involvement was diagnosed. Shortly
      after starting an oral prednisolone therapy (1 mg/kg body weight), the
      eosinophilia normalized. This therapy was stopped after 2 months and the patient
      is now, 6 months after diagnosis, in normal health. CONCLUSION: As demonstrated
      in this case, eosinophilia requires a broad differential diagnosis. A
      hypereosinophilic syndrome can involve many organs and mimic other diseases. The
      new classification of the hypereosinophilic syndrome from 2006, based on
      pathophysiological insights, may foster better diagnosis and therapy for this
      rare disease.

PMID- 18807234
TI  - [Progressive renal failure in spontaneous-onset cholesterol crystal embolism].
AB  - CASE REPORT: A 69-year-old man was admitted to the authors' hospital with an
      increase of plasma creatinine from 1.4 up to 4.9 mg/dl within 4 months and the
      clinical complaints of painful purple toes, recurrent epistaxis and disturbances
      of equilibrium. His past medical history was remarkable for three transient
      ischemic attacks and the diagnosis of a metabolic syndrome. Magnetic resonance
      imaging showed vasculitis-like lesions in the brain. Eosinophilia and tubular
      proteinuria were detected. Renal insufficiency was caused by cholesterol crystal
      embolism, as shown both by skin and renal biopsy. Aortic plaques were identified
      as the putative source of cholesterol embolization. CONCLUSION: In case of
      rapidly progressive renal failure, cholesterol crystal embolism must be
      considered even without preceding angiography.

PMID- 18807235
TI  - [Wicked coding rules--what if you don't understand them even after reading them
      three times?].

PMID- 18807237
TI  - [Why should Byzantium be considered as a cradle of clinical geriatrics?].
AB  - Generally, roots of today's medical ethics are thought to have sprouted from
      antiquity and from classical Hebraic consciousness, while the origin of hospital
      medicine and institutional nursing of the elderly was assumed in Middle Age and
      in modern times, respectively. But even between these two periods, notably in
      Byzantium (324-1453) there were many famous physicians working with surprising
      skills in many disciplines such as surgery and ophthalmology. The most important
      achievement of that time, however, was in public health care. Following the
      Christian ideal of philanthropy, numerous hospitals (nosokomeia), hospices
      (xenodocheia) and asylums for the elderly (gerokomeia) of a remarkable
      organisation and professionalism were founded in many cities of the Byzantine
      Empire. Concerning the elderly patients, interesting findings were obtained
      concerning ageing process (eschatogeria), geriatric symptoms, multimorbidity,
      marasm and typically occurring diseases. Interesting approaches were realized
      with regard to the nursing care, diet and recommended life style for the elderly.
      By the end of the Byzantium Empire in 1453 and due to the different cultural
      development in the West, which was sometimes marked by conflicts between church
      and science and by the regulations of medicine, the knowledge about the Byzantine
      health care was almost lost. It survived, however, only in hospitals of
      occidental monastic orders, which brought their experience from East
      Mediterranean area. Their hospitals were than a base for modern health care and
      for geriatrics.

PMID- 18807238
TI  - [Trans-cultural geriatrics: an incipient challenge].
AB  - Besides extended life expectancy, the globalization, increased mobility and
      migration are additionally influencing the structural change of the society.
      Thereafter, the problem of multiculturalism, as known within the school system,
      will soon also become relevant in the geriatrics. Thus, being in a foreign
      country as an elderly person can aggravate the common geriatric problem of
      isolation. Because of better communication, compliance as well as better quality
      of life, one should strive for empathy between physician and patient. This
      requires the physician's sensibility for individual aspects of the patient's
      history, as well as knowledge, or at least a readiness for learning more about
      other cultures, religions and traditions. Specifically, fundamental aspects of
      Islam, Eastern Christianity, Judaism and Far-East religious and cultural
      understanding are presented.

PMID- 18807239
TI  - [Chemical restraints in nursing homes in the federal state Vorarlberg, Austria-
      an analysis of nursing home documentation according to legal obligation and
      suggestions for future improvement].
AB  - High prevalence of chemical restraints in nursing homes is being criticised as
      suboptimal care. According to a new legal act, the Austrian
      "Heimaufenthaltsgesetz" 2005, nursing homes are obliged to report not only
      physical restraints but also chemical restraints. Using the Beers criteria we
      analysed all 78 notifications of chemical restraints registered during 18 months.
      Pronounced deficits concerning the selection of reporting criteria and the
      quality of doctors' documentation of prescription were observed. National
      guidelines defining chemical restraints and providing valid assessment
      instruments are urgently warranted.

PMID- 18807240
TI  - [Stem cells--cloning, plasticity, bioethic].
AB  - Stem cells with certain characteristics have become promising tools for molecular
      medicine. They have the potential to self-regenerate and to differentiate into
      specific tissues. Besides their great potential, embryonic stem cells (ESC) run
      the risk of enhanced tumorigenesis. The use of human embryonic stem cells (hESC)
      is ethically problematic because their isolation involves the destruction of
      human embryos. Recently developed methods generate are able to pluripotent stem
      cells from fibroblasts. Alternatives for ESC are adult stem cells (ASC) derived
      from bone marrow, cord blood, amniotic fluid and other tissues. The following
      article is on the basis of testimony of Lukas Kenner for the German Bundestag
      about the use of ESC for research, therapy and drug development. Ethical aspects
      are taken into consideration.

PMID- 18807241
TI  - [Arterial hypertension due to altitude].
AB  - The behavior of blood pressure under hypoxic conditions depends on individual
      factors, altitude and duration of stay at altitude. While most humans are
      normotensive at higher altitudes, a few will react with moderate hypertension or
      hypotension. Excessive elevation of arterial blood pressure is not even to be
      expected below 4,000 m. Rather, several weeks' stay at higher altitude will
      decrease systolic and diastolic blood pressure at rest as well as during physical
      exertion. A high-altitude treatment for rehabilitation purposes at moderate
      altitude may be recommended for patients with cardio-circulatory disorders.
      Improvements can last several months even after returning to accustomed
      altitudes. Furthermore, endurance-trained hypertensive patients with
      pharmacologically controlled arterial blood pressure might be able to participate
      in mountain treks without additional health risk.

PMID- 18807242
TI  - [Sudden cardiac death 43 months after fulminant myocarditis and two-peaked
      myositis in non-typhoid salmonellosis].
AB  - HISTORY AND CLINICAL FINDINGS: A previously healthy 29-year-old male was
      hospitalized due to acute myalgia and high temperature following an uncomplicated
      gastroenteritis. Within 24 hours, he developed life-threatening hemodynamic shock
      with the need for inotropic support and sustained ventricular tachycardia.
      INVESTIGATIONS: Echocardiography and electrocardiogram as well as lab tests were
      consistent with the diagnosis of fulminant myocarditis and acute myositis.
      Serological and bacteriological analysis yielded an acute infection with
      salmonella D. TREATMENT AND COURSE: The patient's condition stabilized under
      conservative supportive care within a few days. Apart from a histologically
      confirmed recurrent myositis four weeks later, no further complications occurred
      and the patient was clinically and echocardiographically considered to be in
      complete functional remission. Three and a half years later, however, the patient
      unexpectedly and suddenly died. CONCLUSIONS: Although fulminant myocarditis is a
      life-threatening condition in its initial phase, the prognosis after recovery is
      considered to be good. However, this case study suggests that sudden cardiac
      death as a late complication of fulminant myocarditis may occur.

PMID- 18807244
TI  - [Health Technology Assessment--evaluating health care interventions].
AB  - The evaluation of health interventions has become internationally known as Health
      Technology Assessment (HTA) and has received increased attention as an instrument
      for supporting policy decisions in health care in recent years. HTA is a
      multidisciplinary process that summarises information about the medical, social,
      economic and ethical issues related to the use of new, and established health
      interventions in a systematic, transparent, unbiased, robust manner. HTA strives
      to provide pertinent information to help formulate safe and effective health
      policies that focus on the patient while aiming to achieve the best use of assets
      available.

PMID- 18807245
TI  - Binding of the novel radioligand [(3)H]UFP-101 to recombinant human and native
      rat nociceptin/orphanin FQ receptors.
AB  - Nociceptin/orphanin FQ (N/OFQ) is the endogenous ligand for the N/OFQ peptide
      receptor (NOP). Binding studies have relied on [leucyl-(3)H]N/OFQ, but as this is
      an agonist G-protein coupling will affect affinity. In this paper, we describe a
      new [(3)H]labeled NOP antagonist, [Nphe(1),4'-(3)H-Phe(4),Arg(14),Lys(15)]N/OFQ
      NH(2) ([(3)H]UFP-101). We have characterized [(3)H]UFP-101 at recombinant human
      NOP expressed in Chinese hamster ovary cells (CHO(hNOP)) and native rat NOP in
      cerebrocortex. Radioligand saturation and competition studies were performed on
      membranes, and [(3)H]UFP-101 (antagonist) was compared with [(3)H]N/OFQ
      (agonist). The effects of GTPgammaS (10 microM) and Na(+) were investigated alone
      and in combination in competition experiments with both radioligands. In
      CHO(hNOP), B (max), and pK (D), values were 561 and 580 fmol mg protein(-1) and
      9.97 and 10.19 for [(3)H]UFP-101 and [leucyl-(3)H]N/OFQ, respectively. In rat
      cerebrocortex B (max) and pK (D), values were 65 and 88 fmol mg protein(-1) and
      10.12 and 10.34 for [(3)H]UFP-101 and [leucyl-(3)H]N/OFQ. The binding of both
      radioligands was displaced by a range of peptide and non-peptide NOP ligands at
      both isoforms with good correlation (r (2) 0.92 in Rat and 0.97 in CHO(hNOP)).
      Naloxone was inactive. The binding of both radioligands was Na(+)-dependent with
      [(3)H]UFP-101 being more sensitive (IC(50) approximately20 mM). Unlike the
      agonist [leucyl-(3)H]N/OFQ, the antagonist [(3)H]UFP-101 was unaffected by
      GTPgammaS. [(3)H]UFP-101 binds to human and rat NOP with high affinity and good
      agreement with standard [leucyl-(3)H]N/OFQ in competition experiments. In
      addition, the binding of [(3)H]UFP-101 is unaffected by GTPgammaS. This
      radioligand will be useful to further characterize NOP in a range of binding
      paradigms.

PMID- 18807246
TI  - Naltrexone attenuation of conditioned but not primary reinforcement of nicotine
      in rats.
AB  - RATIONALE: Opioid neurotransmission has been implicated in reinforcement-related
      processes for several drugs of abuse, including opiates, stimulants, and alcohol.
      However, less is known about its role in the motivational effects of nicotine and
      nicotine-associated environmental cues. OBJECTIVE: This study investigated
      whether pretreatment with naltrexone, an opioid receptor antagonist, alters
      conditioned incentive salience of nicotine cues under two conditions: cue-induced
      reinstatement of nicotine-seeking after extinction and cue-maintained responding
      during extinction. The effect of naltrexone on nicotine self-administration
      during the maintenance phase was also examined. MATERIALS AND METHODS: Male
      Sprague-Dawley rats were trained in daily 1-h sessions to self-administer
      nicotine (0.03 mg/kg/infusion, i.v.) on a fixed-ratio 5 schedule and associate a
      conditioned stimulus (CS) with each nicotine delivery. Once responding was
      extinguished by saline substitution for nicotine and omission of the CS, the
      reinstatement tests were conducted following subcutaneous administration of
      naltrexone (0, 0.25, 1, 2 mg/kg). In separate groups of rats, naltrexone (0, 2
      mg/kg) was chronically given before each extinction sessions, where responses on
      the active lever resulted in presentations of the CS without nicotine infusion
      (saline substitution). Self-administration/naltrexone tests were conducted in
      different groups of rats receiving similar nicotine self-administration training.
      RESULTS: Naltrexone significantly attenuated the CS-reinstated responding on the
      active, previously nicotine-reinforced lever in the reinstatement tests and the
      CS-maintained active lever responding during the extinction tests. In contrast,
      neither acute nor chronic naltrexone produced an effect on nicotine self
      administration behavior. CONCLUSIONS: These results indicate that activation of
      opioid receptors is implicated in mediation of the conditioned incentive
      properties of nicotine cues but not in the maintenance of nicotine self
      administration. Therefore, these findings suggest that opioid receptor
      antagonists might have clinical potential for prevention of smoking relapse
      associated with exposure to environmental cues.

PMID- 18807247
TI  - Preliminary evidence of cannabinoid effects on brain-derived neurotrophic factor
      (BDNF) levels in humans.
AB  - BACKGROUND: Acute and chronic exposure to cannabinoids has been associated with
      cognitive deficits, a higher risk for schizophrenia and other drug abuse.
      However, the precise mechanism underlying such effects is not known. Preclinical
      studies suggest that cannabinoids modulate brain-derived neurotrophic factor
      (BDNF). Accordingly, we hypothesized that Delta(9)-tetrahydrocannabinol (Delta(9)
      THC), the principal active component of cannabis, would alter BDNF levels in
      humans. MATERIALS AND METHODS: Healthy control subjects (n = 14) and light users
      of cannabis (n = 9) received intravenous administration of (0.0286 mg/kg)
      Delta(9)-THC in a double-blind, fixed order, placebo-controlled, laboratory
      study. Serum sampled at baseline, after placebo administration, and after
      Delta(9)-THC administration was assayed for BDNF using ELISA. RESULTS: Delta(9)
      THC increased serum BDNF levels in healthy controls but not light users of
      cannabis. Further, light users of cannabis had lower basal BDNF levels. Delta(9)
      THC produced psychotomimetic effects, perceptual alterations, and "high" and
      spatial memory impairments. IMPLICATIONS: The effects of socially relevant doses
      of cannabinoids on BDNF suggest a possible mechanism underlying the consequences
      of exposure to cannabis. This may be of particular importance for the developing
      brain and also in disorders believed to involve altered neurodevelopment such as
      schizophrenia. Larger studies to investigate the effects of cannabinoids on BDNF
      and other neurotrophins are warranted.

PMID- 18807248
TI  - The discriminative stimulus effects of dopamine D2- and D3-preferring agonists in
      rats.
AB  - RATIONALE: Previous research has found the stimulus effects of dopamine D2- and
      D3-preferring agonists difficult to distinguish in drug discrimination studies.
      Antagonism studies suggest that the stimulus effects of both types of agonists
      may be mediated primarily through D2 receptors. OBJECTIVES: The current study was
      designed to further assess the receptors mediating the stimulus effects of these
      agonists and to attempt to train rats to discriminate directly between D2- and D3
      preferring dopamine agonists. MATERIALS AND METHODS: Four groups of eight rats
      were trained to discriminate either 0.1 mg/kg of the D3-preferring agonist
      pramipexole from saline, 1.0 mg/kg of the D2-preferring agonist sumanirole from
      saline, 0.1 mg/kg pramipexole from either saline or 1.0 mg/kg sumanirole, or 1.0
      mg/kg sumanirole from either saline or 0.1 mg/kg pramipexole. RESULTS: Three of
      eight rats in the 0.1 mg/kg pramipexole vs. 1.0 mg/kg sumanirole or saline failed
      to meet the training criteria, and the discrimination in this group was tenuous.
      The D2-preferring antagonist L-741,626 at 1.0 mg/kg was more effective at
      shifting to the right the pramipexole dose-response curve in pramipexole-trained
      rats, while 32 mg/kg of the selective D3 antagonist PG01037 had little effect.
      Quinpirole and 7-OH-DPAT fully or partially substituted for both pramipexole and
      sumanirole in each group tested, while cocaine did not substitute in any group.
      CONCLUSIONS: Antagonist data along with the pattern of training and substitution
      data suggested that D2 receptor activation is primarily responsible for the
      stimulus effects of both sumanirole and pramipexole with D3 receptor activation
      playing little or no role.

PMID- 18807249
TI  - A within-subject assessment of the discriminative stimulus and reinforcing
      effects of self-administered cocaine in rhesus monkeys.
AB  - RATIONALE: Drug discrimination (DD) and drug self-administration (SA) are
      frequently used preclinical assays. All preclinical studies with cocaine have
      examined the discriminative stimulus (S(D)) and reinforcing (S(R)) effects in
      separate groups of subjects. OBJECTIVE: The objective of the study is to train
      drug-naive rhesus macaques to discriminate self-administered cocaine from saline
      and to assess S(D) and S(R) effects using a within-subjects design. MATERIALS AND
      METHODS: Adult male rhesus monkeys (n = 4) were trained to self-administer
      cocaine (0.1 mg/kg per injection) under a progressive-ratio (PR) reinforcement
      schedule. Next, they were trained to discriminate self-administered cocaine (0.45
      or 0.56 mg/kg) or saline under a fixed-ratio (FR) 50 schedule of food
      presentation. The final schedule combined DD and SA into a multiple [chained FR
      50 SA (cocaine or saline), food-reinforced DD] and PR SA schedule. RESULTS: Each
      subject acquired SA under a PR schedule with significant differences in
      breakpoint between saline and cocaine evident by session 5. Self-administered
      cocaine was established as an S(D), such that 80% of responding before delivery
      of the first reinforcer and 90% of all responding occurred on the injection
      appropriate lever. In all monkeys, there was at least one cocaine dose that did
      not engender cocaine-appropriate responding during DD (i.e., <20% cocaine
      appropriate responding) yet functioned as a reinforcer during PR SA, suggesting
      that cocaine-like S(D) effects are not necessary for cocaine reinforcement.
      CONCLUSIONS: This within-subject model may provide new information related to the
      behavioral mechanisms of action leading to the high abuse potential of cocaine;
      such information may lead to novel pharmacological treatment strategies for
      addiction.

PMID- 18807250
TI  - Acute nicotine changes dynorphin and prodynorphin mRNA in the striatum.
AB  - RATIONALE: Nicotine displays rewarding and aversive effects, and while dopamine
      has been linked with nicotine's reward, the neurotransmitter(s) involved with
      aversion remains speculative. The kappa-dynorphinergic system has been associated
      with negative motivational and affective states, and whether dynorphin (Dyn)
      contributes to the behavioral pharmacology of nicotine is a pertinent question.
      OBJECTIVE: We determined whether administration of a single dose of nicotine
      alters the biosynthesis of Dyn in the striatum of mice. RESULTS: Nicotine free
      base, 1 mg/kg, sc, induced a biphasic, protracted increase of striatal Dyn, an
      initial rise by 1 h, which declined to control levels by 2 h, and a subsequent
      increase, between 6 and 12 h, lasting over 24 h. At 1 h, the nicotine effect was
      dose dependent, with doses>or=0.5 mg/kg inducing a response. Prodynorphin mRNA
      increased by 30 min for over 24 h, and in situ hybridization demonstrated
      elevated signal in caudate/putamen and nucleus accumbens. The nicotinic
      antagonist mecamylamine prevented the Dyn response, and a similar effect was
      observed with D1- and D2-like dopamine receptor antagonists, SCH 23390,
      sulpiride, and haloperidol. The glutamate NMDA receptor antagonist MK-801
      reversed the nicotine-induced increase of Dyn, while the AMPA antagonist NBQX had
      a marginal effect. CONCLUSIONS: We interpret our findings to indicate that acute
      nicotine enhances the synthesis and release of striatal Dyn. We propose that
      nicotine influences Dyn primarily through dopamine release and that glutamate
      plays a modulatory role. A heightened dynorphinergic tone may contribute to the
      aversive effects of nicotine in naive animals and first-time tobacco smokers.

PMID- 18807251
TI  - Population pharmacokinetics of darbepoetin alpha in peritoneal dialysis and non
      dialysis patients with chronic kidney disease after single subcutaneous
      administration.
AB  - OBJECTIVE: To characterize the pharmacokinetics of darbepoetin alpha and
      covariate relationships in chronic kidney disease (CKD) patients after a single
      subcutaneous administration. METHODS: A total of 989 serum concentration
      recordings from 64 patients were analyzed using NONMEM with a model including
      endogenous erythropoietin production. The basic and final models were evaluated
      for stability using bootstrapping. RESULTS: The selected basic model had one
      compartment with a combination of the additive and constant coefficient of
      variation error models for residual variability. The significant covariate was
      weight for apparent clearance (CL/f) and apparent volume of central compartment
      (V(1)/f). The typical values of CL/f, V(1)/f, and absorption rate constant were
      0.158 l/h, 13.7 l, and 0.0376/h, respectively. Evaluation by bootstrapping showed
      that the final model was stable. CONCLUSION: The present analysis indicated that
      weight is a significant covariate for CL/f and V(1)/f. However, dosage adjustment
      according to weight is not necessary for subcutaneous administration of
      darbepoetin alpha in CKD patients.

PMID- 18807252
TI  - Combined intervention programme reduces inappropriate prescribing in elderly
      patients exposed to polypharmacy in primary care.
AB  - PURPOSE: To evaluate the effect of a combined or a single educational
      intervention on the prescribing behaviour of general practitioners (GPs). The
      primary endpoint was effect on inappropriate prescribing according to the
      Medication Appropriateness Index (MAI). METHODS: General practitioners were
      randomised to either (1) a combined intervention consisting of an interactive
      educational meeting plus feedback on participating patients' medication, (2) a
      single intervention with an interactive educational meeting or (3) a control
      group (no intervention). Elderly (>65 years) patients exposed to polypharmacy
      (>or=5 medications) were identified and approached for inclusion. Data on
      medications prescribed over a 3-month period were collected, and the GPs provided
      detailed information on their patients before and after the intervention. A pre-
      and post-MAI were scored for all medications. RESULTS: Of the 277 GPs invited to
      participate; 41 (14.8%) volunteered. Data were obtained from 166 patients before
      and after the intervention. Medication appropriateness improved in the combined
      intervention group but not in the single intervention group. The mean change in
      MAI and number of medications was -5 [95% confidence interval (CI) -7.3 to -2.6]
      and -1.03 (95% CI -1.7 to -0.30) in the combined intervention group compared with
      the group with the educational meeting only and the no intervention group.
      CONCLUSIONS: A combined intervention consisting of an interactive educational
      meeting plus recommendations given by clinical pharmacologists/pharmacists
      concerning specific patients can improve the appropriateness of prescribing among
      elderly patients exposed to polypharmacy. This study adds to the limited number
      of well-controlled, randomised studies on overall medication appropriateness
      among elderly patients in primary care. Important limitations to the study
      include variability in data provided by participating GPs and a low number of GPs
      volunteering for the study.

PMID- 18807253
TI  - Rheumatoid cranial pachymeningitis successfully treated with long-term
      corticosteroid.
AB  - We report a 68-year-old man without clinical history of rheumatoid arthritis who
      presented with acute bilateral palsy of the IX and X cranial nerves secondary to
      pachymeningitis confirmed on cranial MRI. Rheumatoid factor in both serum and
      cerebrospinal fluid and anti-agalactosyl IgG antibody in serum were positive. The
      radiographs of hands and feet revealed signs of early rheumatism. The dural
      biopsy specimen showed chronic inflammation with infiltration of lymphocytes and
      histiocytes. A diagnosis of rheumatoid cranial pachymeningitis was made.
      Treatment with long-term corticosteroid was excellently effective.

PMID- 18807254
TI  - Induction of remission in rheumatoid arthritis: criteria and opportunities.
AB  - The concept of remission in rheumatology is complicated by the lack of a single
      gold standard measurement, spontaneous remissions and the usage of several sets
      of remission criteria. Feasibility is reduced by traditional clinical practice,
      which does not include remission criteria monitoring. The "window of opportunity"
      to prevent joint damage with DMARD therapy lasts only a few months. The
      perspective of the physician and patient differ, as the former gives importance
      to signs of disease activity, whereas the latter to disability and quality of
      life. All patients with rheumatoid arthritis are candidates for combination DMARD
      based therapy, which should be instituted without delay. Remission is important
      to prevent joint destruction, preserve adequate quality of life and prevent
      disability. The introduction of biological agents has made this objective
      feasible, but the failure rate is still high (about 50%), on account of lack of
      response, contraindications and intolerance.

PMID- 18807255
TI  - Partial AZFc deletions and duplications: clinical correlates in the Italian
      population.
AB  - The role of partial AZFc deletions of the Y chromosome in spermatogenic
      impairment is currently debated. Recently, it was also reported that duplications
      of the same region are associated with oligozoospermia in Han-Chinese men. The
      aims of this study were (1) to evaluate the clinical significance of partial AZFc
      deletions in a large study population and (2) to define if partial AZFc
      duplications are a risk factor for spermatogenic failure also in a Caucasian
      population such as the Italian. We screened 556 infertile patients and 487
      normozoospermic controls for partial AZFc deletions with a combined method based
      on STS+/- followed by CDY1-DAZ gene dosage and copy analysis. For the second aim,
      we performed CDY1-DAZ gene dosage in 229 infertile patients and 263
      normozoospermic controls. The frequency of gr/gr deletions in patients was
      significantly different from the controls (3.2 vs. 0.4%, respectively; P <
      0.001), with an OR = 7.9 (95% CI 1.8-33.8). b2/b3 deletions were rare in both
      groups (0.5% in patients, 0.2% in controls). Concerning gr/gr duplications, we
      observed no significant differences in their frequency between cases (2.6%) and
      controls (3.8%). This is the largest study population in the literature in which
      all potential methodological and selection biases were carefully avoided to
      detect the clinical significance of partial AZFc deletions and duplications. Our
      study provides strong evidence that gr/gr deletion is a risk factor for impaired
      spermatogenesis, whereas we did not detect a significant effect of b2/b3
      deletions and partial AZFc duplications on spermatogenesis in this Caucasian
      ethnic group.

PMID- 18807256
TI  - Genetic regulation of amniotic fluid TNF-alpha and soluble TNF receptor
      concentrations affected by race and preterm birth.
AB  - Racial disparity in spontaneous preterm birth (PTB) between African Americans and
      Caucasians in the US is unexplained, but is probably related to differences in
      amniotic fluid (AF) inflammatory cytokine profiles. Therefore, this study
      analyzed the association of 34 single nucleotide polymorphisms (SNPs) in TNF
      alpha and its receptor genes (TNFR1 and TNFR2) with AF TNF-alpha and soluble TNF
      receptor (R1 and R2) concentrations in PTB. Samples consisted of African American
      and Caucasian cases (PTB), and controls (term birth) for which both cytokine, and
      maternal and fetal genotype data were available. Analyses were performed with
      genotype, case, and maker-status interaction in the model for log transformed
      cytokine concentrations. In Caucasians, two interactions between genotype and
      pregnancy outcome associated with cytokine concentrations, whereas 14 gene
      variants in African Americans showed interactions with pregnancy outcome, and 13
      showed association with genetic markers. In conclusion, cytokine concentrations
      in African American preterm births can be partially explained by interactions
      between pregnancy outcome, SNPs and infection. This does not appear to be the
      case in Caucasians. These findings may be important in understanding disparity in
      rates of PTB between the two populations.

PMID- 18807257
TI  - Conidia of Trichoderma virens as a phosphorus source for mycorrhizal Pinus
      sylvestris seedlings.
AB  - In this study, the mobilization and further translocation of phosphorus from
      conidia of saprotrophic fungus Trichoderma virens into Pinus sylvestris seedlings
      by nondestructive measuring of (32)P was assessed. The radioactive phosphorus
      flux from the conidia to the Scots pine seedlings forming mycorrhiza with
      Laccaria laccata and Suillus bovinus amounted up to 27.82% and 7.42%,
      respectively, on the 28th day of the experiment, while at the same time in
      nonmycorrhizal pine seedlings, the detected radioactivity reached only 0.56%. Our
      studies revealed that both ectomycorrhizal fungi: L. laccata and S. bovinus,
      mobilized the phosphorus from radioactive conidia of T. virens. On this basis, we
      conclude that activities of the mycosymbionts may facilitate absorption and
      further translocation of phosphorus from organic matter into the host plants.

PMID- 18807258
TI  - Ectomycorrhizal characterization of an American chestnut (Castanea dentata)
      dominated community in Western Wisconsin.
AB  - Circa 1900, a farmer from the eastern US planted 11 American chestnut (Castanea
      dentata) seeds on a newly established farm near West Salem in western Wisconsin.
      These trees were very successful, producing a large stand of over 6,000 trees.
      Since this area is well outside the natural range of chestnut, these trees
      remained free from chestnut blight until 1987. In the West Salem stand, chestnuts
      are the dominant species of a mixed forest community, reminiscent of the chestnut
      oak ecosystems of pre-1900 Appalachia. To identify putative mycorrhizal
      associates of chestnut in this unique forest, our approach was twofold: (1) an
      extensive fruiting body survey was conducted for four seasons that yielded
      approximately 100 putative mycorrhizal species and (2) a belowground molecular
      approach was used to generate DNA sequences of the internal transcribed spacer
      region from ectomycorrhizae. Unexpectedly, chestnut did not appear to be the
      dominant underground ectomycorrhizal-forming plant species. This study highlights
      the need to identify the plant host species when conducting belowground molecular
      based surveys and provides preliminary identification of ectomycorrhizal fungi
      associated with a disjunct stand of American chestnut.

PMID- 18807260
TI  - Fabrication and biological characteristics of beta-tricalcium phosphate porous
      ceramic scaffolds reinforced with calcium phosphate glass.
AB  - The fabrication process, compressive strength and biocompatibility of porous beta
      tricalcium phosphate (beta-TCP) ceramic scaffolds reinforced with 45P(2)O(5)
      22CaO-25Na(2)O-8MgO bioglass (beta-TCP/BG) were investigated for their
      suitability as bone engineering materials. Porous beta-TCP/BG scaffolds with
      macropore sizes of 200-500 muicrom were prepared by coating porous polyurethane
      template with beta-TCP/BG slurry. The beta-TCP/BG scaffolds showed interconnected
      porous structures and exhibited enhanced mechanical properties to those pure beta
      TCP scaffolds. In order to assess the effects of chemical composition of this
      bioglass on the behavior of osteoblasts cultured in vitro, porous scaffolds were
      immersed in simulated body fluid (SBF) for 2 weeks, and original specimens
      (without soaked in SBF) seeded with MC3T3-E1 were cultured for the same period.
      The ability of inducing apatite crystals in simulated body fluid and the
      attachment of osteoblasts were examined. Results suggest that apatite
      agglomerates are formed on the surface of the beta-TCP/BG scaffolds and its Ca/P
      molar ratio is approximately 1.42. Controlling the crystallization from the beta
      TCP/BG matrix could influence the releasing speed of inorganic ions and further
      adjust the microenvironment of the solution around the beta-TCP/BG, which could
      improve the interaction between osteoblasts and the scaffolds.

PMID- 18807261
TI  - Enrichment of anodic MgO layers with Ag nanoparticles for biomedical
      applications.
AB  - The growing fight against infections caused by bacteria poses new challenges for
      development of materials and medical devices with antimicrobial properties.
      Silver is a well known antimicrobial agent and has recently started to be used in
      nanoparticulate form, with the advantage of a high specific surface area and a
      continuous release of enough concentration of silver ions/radicals. The synthesis
      of MgO-Ag nanocomposite coatings by in situ deposition of silver nanoparticles
      during plasma electrolytic oxidation of a magnesium substrate is presented in
      this study. The process was performed in an electrolyte containing Ag
      nanoparticles under different oxidation conditions (i.e., current density,
      oxidizing time, silver nanoparticles concentration in the electrolyte). Surface
      morphology, phase composition and elemental composition (on the surface and
      across the thickness of MgO-Ag nanocomposite coatings) were assessed by scanning
      electron microscopy, X-ray diffraction, energy X-ray dispersive spectrometry and
      radio frequency glow discharge optical emission spectroscopy, respectively. The
      coatings were found to be porous, around 7 mum thick, consisting of a crystalline
      oxide matrix embedded with silver nanoparticles. The findings suggest that plasma
      electrolytic oxidation process has potential for the synthesis of MgO-Ag
      nanocomposite coatings.

PMID- 18807262
TI  - Cellular uptake of gold nanoparticles directly cross-linked with carrier peptides
      by osteosarcoma cells.
AB  - Nanoparticles have been extensively used for a variety of biomedical applications
      and there is a growing need for highly specific and efficient delivery of the
      nanoparticles into target cells and subcellular location. We attempted to
      accomplish this goal by modifying gold particles with peptide motif's that are
      known to deliver a 'cargo' into chosen cellular location specifically, we
      intended to deliver nanogold particles into cells through chemical cross-linking
      with different peptides known to carry protein into cells. Our results suggest
      that specific sequence of such 'carrier peptides' can efficiently deliver gold
      nanoparticles into cells when chemically cross-linked with the metal particles.

PMID- 18807263
TI  - CD41 Western blotting: a new method to detect platelet adhesion to artificial
      surfaces used in extracorporeal circulation procedures.
AB  - Cardiopulmonary bypass (CPB) surgery is associated with platelet activation and
      reduced platelet counts due to artificial surface activation of blood elements
      and non-physiological flow-patterns. As shown in former studies, coating of
      medical devices can improve hemocompatibility in extracorporeal circulation
      systems. In this study, we demonstrate a new method to determine platelet
      adhesion on 18 coated and non-coated membrane oxygenators in a simulated CPB
      model with CD41 Western blot. Platelet loss and the release of beta-TG (platelet
      activation marker) were determined during a 120 min recirculation phase. At the
      end of the run the membrane oxygenators (with tubing system) were rinsed and the
      amount of adsorbed proteins on the surface was analyzed by using sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting
      technique. Uncoated devices showed significantly higher concentrations of CD41
      and of fibrinogen adsorption compared to the coated membrane oxygenators. These
      results correspond with the release of beta-TG and platelet loss indicating less
      platelet adhesion on the coated oxygenators compared with the uncoated group.
      This new method may be useful in choosing less platelet activating materials for
      all kind of blood contacting devices to improve thrombogenicity including
      platelet functionality.

PMID- 18807264
TI  - Effect of PEG amount in amorphous calcium phosphate on its crystallized products.
AB  - Biphasic alpha-tricalcium phosphate/beta-tricalcium phosphate (alpha/beta-TCP)
      with a designed phase ratio is thought to have controllable dissolution
      reprecipitation behavior that is significant in the repair and regeneration of
      bone. Amorphous calcium phosphate (ACP) was selected as a precursor to prepare
      biphasic alpha/beta-TCP. The influence of polyethylene glycol (PEG) content in
      ACP on its crystallization, or on the phase ratio of the resulting biphasic TCP,
      was investigated. ACP was synthesized by the reaction of Ca(NO(3))(2) with
      (NH(4))(2)HPO(4) using PEG as an additive. Depending on the amount of PEG
      addition, resulting ACP could be crystallized to alpha-TCP, beta-TCP or biphasic
      alpha/beta-TCP after heat-treatment at 800 degrees C, showing that PEG addition
      is a critical factor to tailor the phase ratio of biphasic alpha/beta-TCP. One
      reason for the influence of PEG is that ACP with different PEG content could have
      two types of unit structures that tend to form alpha-TCP and beta-TCP after
      crystallization.

PMID- 18807265
TI  - Effect of hydrolysis on mechanical properties of tricalcium phosphate/poly-L: 
      lactide composites.
AB  - In order to investigate hydrolysis behavior and associated variation in
      mechanical properties of bioresorbable plastic composites, beta-tricalcium
      phosphate (beta-TCP)/poly(L: -lactide) (PLLA), the immersion tests into phosphate
      buffered solution (PBS) with different pH were conducted. After the immersion
      tests, tensile, bending and compressive tests were conducted on the specimen. The
      significant decrease in the mechanical properties of the specimens with 5.0 wt%
      beta-TCP contents were not observed in the pH = 7.4 immersion tests, whereas
      significant decrease were observed for the specimen with 9.5 and 14.0 wt%
      contents after 24 weeks. In the pH = 6.4 immersion tests, the degradation was
      accelerated. From the fracture surface observation, debondings between beta-TCP
      and PLLA grew into the void shape in the ductile fracture surface before
      immersion tests, whereas the voids were observed in the brittle fracture surface
      after immersion tests. This is due to the bioresorption of beta-TCP particles
      and/or beta-TCP/PLLA interface. In order to discuss the degradation of mechanical
      properties, tensile modulus degradation was analyzed based on the micromechanics
      supposing the damaged particles as voids. Degradation tendency predicted was in
      good agreement with experimental results. These results suggested that the
      degradation in modulus was attributed to lower load capacity of beta-TCP
      particles and lower load transfer to beta-TCP particles due to the hydrolysis of
      the beta-TCP particles and the interface between beta-TCP and PLLA.

PMID- 18807266
TI  - Bioactive borosilicate glass scaffolds: improvement on the strength of glass
      based scaffolds for tissue engineering.
AB  - Three-dimensional macroporous scaffolds with the pore size of 200-500 mum were
      fabricated by replication method using bioactive borosilicate glass from Na(2)O
      K(2)O-MgO-CaO-SiO(2)-P(2)O(5)-B(2)O(3) system. The effects of the strength of the
      strut in reticulated scaffold, as well as the geometrical parameter of the
      scaffold on the strength of reticulated scaffold were investigated. Scanning
      electron microscope (SEM) and X-ray diffraction (XRD) results show that the
      solidified glass struts in the reticulated scaffold could be obtained through a
      sufficient vicious flow of glass, during the fabrication. By increasing the solid
      content in slurries, from which the scaffold was made, the load-bearing units of
      the reticulated scaffold switch from struts to the walls between the pores, and
      the compressive strength dramatically climbs higher than the theoretical strength
      calculated by Gibson model. In particular, the compressive strength of the
      reticulated scaffold, as high as approximately 10 MPa with the porosity of
      approximately 70%, is close to the reported compressive values of human
      cancellous bone. This indicates the bioactive borosilicate glass-based scaffold
      is a promising candidate for bone tissue engineering.

PMID- 18807267
TI  - A nonsense mutation (E1978X) in the ATM gene is associated with breast cancer.
AB  - Blood relatives of patients with ataxia-telangiectasia (A-T) have an increased
      risk to develop breast cancer. Allelic heterogeneity has made it difficult to
      confirm the role of ATM, the gene mutated in A-T, for breast cancer
      susceptibility in the general population. We now report that a nonsense mutation,
      p.E1978X (c.5932G>T), is both a classical A-T mutation and a breast cancer
      susceptibility allele in Eastern European populations. In a case-control study
      from Belarus, the E1978X mutation was identified in 10/1,891 Byelorussian breast
      cancer cases (0.5%) compared with 1/1,019 population controls [odds ratio (OR):
      5.4; 95% confidence interval (95% CI), 0.7-42.4, P = 0.1]. A second case-control
      study from Russia identified the E1978X mutation in two Russian and one Ukrainian
      cases out of 611 breast cancer patients but not in any Russian or Ukrainian
      controls (P = 0.1). In a third case-control study from Poland, E1978X was
      observed in 7/3,910 Polish breast cancer cases (0.2%) compared with 1/2,010
      cancer-free population controls (OR: 3.6; 95% CI: 0.4-29.3, P = 0.4). In the
      combined analysis, E1978X was significantly associated with breast cancer (Mantel
      Haenszel OR: 5.6, 95% CI: 1.3-21.4, P = 0.01). Taken together, this study
      provides first evidence for the association of a common A-T causing mutation with
      breast cancer in Eastern European founder populations.

PMID- 18807268
TI  - About the c.156_157insAlu BRCA2 breast cancer predisposing mutation.

PMID- 18807269
TI  - The impact of preoperative MRI on breast-conserving surgery of invasive cancer: a
      comparative cohort study.
AB  - AIM: To assess whether preoperative contrast-enhanced magnetic resonance imaging
      (MRI) of the breast influences the rate of incomplete tumor excision. METHODS: In
      a cohort of 349 women with invasive breast cancer, patients eligible for breast
      conserving therapy (BCT) on the basis of conventional imaging and palpation only
      (N = 176) were compared to those who had an additional preoperative MRI (N =
      173). Multivariate analysis was applied to explore associations with incomplete
      tumor excision. RESULTS: MRI detected larger extent of breast cancer in 19 women
      (11.0%), leading to treatment change: mastectomy (8.7%) or wider excision (2.3%).
      Tumor excision was incomplete in 22/159 (13.8%) wide local excisions in the MRI
      group and in 35/180 (19.4%) in the non-MRI group (P = 0.17). Stratified to tumor
      type, incompletely excised infiltrating ductal carcinoma (IDC) was significantly
      associated with absence of MRI: 11/136 (8.1%) versus 2/126 (1.6%) (MRI present)
      (P = 0.02). No significant factors explained incomplete excision of other tumor
      types. CONCLUSION: Preoperative MRI did not significantly affect the overall rate
      of incomplete tumor excision, but it yielded significantly lower rate of
      incompletely excised IDC. The reduction of incomplete excisions after MRI was
      smaller than the rate of a prior treatment change incurred by MRI.

PMID- 18807270
TI  - The organophosphorous pesticide, fenitrothion, acts as an anti-androgen and
      alters reproductive behavior of the male three-spined stickleback, Gasterosteus
      aculeatus.
AB  - Fenitrothion (FN) is a widely used organophosphorous pesticide that has
      structural similarities with the clinical anti-androgen flutamide. The potential
      for FN to act as an anti-androgen (at exposures of 1, 50, and 200 microg FN/l
      over a 26-day period) was assessed in male three-spined sticklebacks,
      Gasterosteus aculeatus, by measuring kidney spiggin concentration, nest-building,
      and courtship behavior. Spiggin is the glue protein that male sticklebacks use to
      build their nests and is directly controlled by androgens. FN exposure
      significantly reduced spiggin production as well as nest-building activity. It
      also adversely affected courtship--especially the 'zigzag dance' and biting
      behavior of the males. FN thus appears to have anti-androgenic effects on both
      the physiology and behavior of the male stickleback.

PMID- 18807271
TI  - "Do Real Women Have Curves?" Paradoxical body images among Latinas in New York
      City.
AB  - This paper examines Latinas' assessments of their individual body shape and
      weight vis-a-vis their beliefs and attitudes regarding mainstream and alternative
      body images. A mixed method data collection system was used based on individual
      instruments and focus group guidelines. While individual measures revealed
      participants' preference for thinner body types than what they actually
      considered themselves to be, group data underscore contradictory body paradigms,
      defined as Latinas' Paradoxical Body Images (LAPABI). Findings suggest the
      prevalence of a mainstream stereotype represented by the fit/thin White woman as
      the ultimate body ideal, along with the Latina curvy shape as its counter-image.
      The paper further discusses the importance of the media, and of divergent
      cultural values, in supporting these co-existing body ideals, as well as the need
      for more studies addressing their combined effect on Latinas' obesity patterns
      and their weight-control efforts.

PMID- 18807272
TI  - Readers appreciate JAVMA commentary on good medicine.

PMID- 18807273
TI  - Readers appreciate JAVMA commentary on good medicine.

PMID- 18807274
TI  - Treating tobacco use and dependence: 2008 update U.S. Public Health Service
      Clinical Practice Guideline executive summary.

PMID- 18807275
TI  - [6/7. Social service assistant].

PMID- 18807276
TI  - The fortitude of Vicente Forte and his living  art dedicated to medicine in
      Brazil.

PMID- 18807277
TI  - Separated by death? Burials, cemeteries, and confessional boundaries in
      seventeenth-century France.

PMID- 18807278
TI  - Stop blaming physicians.

PMID- 18807279
TI  - Regarding "Tonsillar microbial flora: a comparison of infected and non-infected
      tonsils".

PMID- 18807280
TI  - The discovery of second sight in late 17th-century Scotland.

PMID- 18807281
TI  - Classifying lust: the seventeenth-century vogue for male love.

PMID- 18807282
TI  - Despite regulatory changes, hospitals cautious in helping physicians purchase
      electronic medical records.
AB  - While hospitals are evaluating strategies to help physicians purchase electronic
      medical records (EMRs) following recent federal regulatory changes, they are
      proceeding cautiously, according to findings from the Center for Studying Health
      System Change's (HSC) 2007 site visits to 12 nationally representative
      metropolitan communities. Hospital strategies to aid physician EMR adoption
      include offering direct financial subsidies, extending the hospital's ambulatory
      EMR vendor discounts and providing technical support. Two key factors driving
      hospital interest in supporting physician EMR adoption are improving the quality
      and efficiency of care and aligning physicians more closely with the hospital. A
      few hospitals have begun small-scale, phased rollouts of subsidized EMRs, but the
      burden of other hospital information technology projects, budget limitations and
      lack of physician interest are among the factors impeding hospital action. While
      it is too early to assess whether the regulatory changes will spur greater
      physician EMR adoption, the outcome will depend both on hospitals' willingness to
      provide support and physicians' acceptance of hospital assistance.

PMID- 18807283
TI  - From natural disability to the moral man: Calvinism and the history of
      psychology.

PMID- 18807284
TI  - [Esotericism as scientific knowledge in Norway in the 17th century].

PMID- 18807286
TI  - [Widows' rights in Valencian local law].

PMID- 18807288
TI  - Utilization and unexpected hospitalization rates of a pediatric emergency
      department 23-hour observation unit.
AB  - OBJECTIVES: The 23-hour observation units (OUs) may be used to avoid unnecessary
      hospital admissions. However, unexpected hospitalizations from the 23-hour OUs
      involve transfer of care and may decrease the efficiency and safety of care of
      the patient and the unit itself. The primary objective of this study was to
      determine the predictors of unexpected hospitalization for admissions to a
      pediatric 23-hour OU. METHODS: This is an observational prospective cohort study
      of patients admitted to a pediatric 23-hour OU. Bivariate and multivariate
      regression analyses identify factors associated with unexpected hospitalization.
      RESULTS: There were 4453 patients admitted to the 23-hour OU during the study.
      The overall rate of unexpected hospitalization was 20.3%; the mean 23-hour OU
      stay was 15 hours. Age, sex, race/ethnicity, and insurance status were not
      associated with increased unexpected hospitalization rates. Multivariate
      regression modeling revealed that unexpected hospitalization was associated with
      subgroups of resources used (intravenous medications and fluids,
      cardiorespiratory monitoring, respiratory therapist use, and supplemental
      oxygen), of subspecialty consultation, and of diagnosis categories (including
      asthma, adenitis, cellulitis, bronchiolitis, and esophageal foreign body
      ingestions). Experience of the health care provider involved in the care of the
      patient was not associated with increased unexpected hospitalization.
      CONCLUSIONS: Most of the patients (80%) were successfully discharged from the 23
      hour OU. Demographics of the patient and practitioner characteristics did not
      influence the risk of unexpected hospitalizations; however, certain patient
      diagnoses, use of resources,and subspecialty consultation did increase the risk
      of unexpected hospitalization and, therefore, may guide future admission criteria
      for pediatric 23-hour OU.

PMID- 18807289
TI  - Quality of orders for medication in the resuscitation room of a pediatric
      emergency department.
AB  - OBJECTIVE: The aim of this study was to evaluate both the errors and completeness
      of orders for intravenous medications and fluids in the resuscitation/trauma room
      of a pediatric emergency department before and after implementation of a standard
      order form. METHODS: After implementing a standard order form in March 2004, a
      retrospective chart review of patients admitted to the resuscitation/trauma room
      of a pediatric tertiary care hospital in March, May, and July 2003 and, again in
      the same months 1 year later, in 2004. The completeness criteria were based on
      recommendations from the Institute for Safe Medication Practice and are the same
      as the ones used in our hospital. Medication errors and their severity were
      classified according to definitions of the American Society of Health-System
      Pharmacists. RESULTS: In the 3 months studied in 2003, 14 (5%) of 276 written
      orders fit the standard of completeness, whereas in the 3 months studied in 2004,
      93 (33%) of 281 were complete. There were 55 (15%) medication errors of 372
      orders in 2003 and 20 (6%) of 347 orders in 2004. Thus, during the 2 study
      periods, there was an increase in completeness (Delta 28%; 95% confidence
      interval, 22%-34%) and a decrease in medication errors (Delta 9%; 95% confidence
      interval, 5%-13%). Most of the errors had no adverse effects on patients.
      However, 11 errors (10 in 2003 and 1 in 2004) required some intervention. Most
      interventions resulted in the need for an additional dose of medication because
      of underdosage. CONCLUSIONS: A standard designated order form was associated with
      an increase in completeness and with a decrease in prescribing errors in the
      resuscitation/trauma room of a pediatric emergency department.

PMID- 18807290
TI  - Metabolic syndrome defined by new criteria in Japanese is associated with
      increased liver enzymes and C-reactive protein.
AB  - Metabolic syndrome (MetS) is characterized by the presence of atherogenic risk
      factors, and is associated with a marked increase in the risk of cardiovascular
      disease. Recently, the criteria of MetS were newly defined in Japan. We examined
      the relationship between MetS and the various metabolic parameters in Japanese
      subjects. This study included 458 Japanese subjects undergoing medical checkups
      at Nagoya University Hospital. New criteria developed by the joint committee of
      eight Japanese medical societies for the clinical recognition of MetS were
      adopted. We examined the association between MetS and various metabolic
      parameters, including liver enzymes (alanine aminotransferase, ALT; gamma
      glutamyltransferase, GGT) and highly sensitive C-reactive protein (hsCRP). The
      mean overall prevalence of MetS was 8.7% (male: 12.9%; female: 2.2%, p = 0.0001).
      MetS was significantly associated with elevated ALT (> 45 IU/L) (OR: 3.37, 95%
      CI: 1.19-9.52, p < 0.05) and GGT (> 64 IU/L in males, > 45 IU/L in females) (OR:
      4.96, 95% CI: 2.31-10.66, p = 0.0001), respectively. MetS was also significantly
      associated with elevated hsCRP (> or = 0.1 ng/mL) (OR: 2.77, 95% CI: 1.20-6.41, p
      < 0.05). Thus, MetS was associated with elevated liver enzymes (especially, GGT),
      and inflammation (hsCRP).

PMID- 18807291
TI  - An association between serotonin receptor 3B gene (HTR3B) and treatment-resistant
      schizophrenia (TRS) in a Japanese population.
AB  - Genetic factors are thought to be involved in the development of treatment
      resistant schizophrenia (TRS). Since several antipsychotic drugs inhibit the
      release of neurotransmitters via the serotonin receptors 3 (5-HT3), a dysfunction
      of this kind of receptor might be associated with the development of TRS. Thus,
      single-marker and haplotype analyses of the tag-single nucleotide polymorphisms
      (SNPs) of the 5-HT3B subunit gene (HTR3B) were performed in TRS (n = 101) and non
      TRS (n = 244) patients. The deletion allele at the 3 bp-insertion/deletion
      polymorphism site (-100_-102delAAG) located in the putative HTR3B promoter region
      is significantly more frequent in the TRS group than the insertion allele by a
      single-marker comparison (p = 0.031). In addition, luciferase promoter assays
      showed that the deletion allele exhibited significantly higher transcriptional
      activity than the insertion allele in COS7 cells (p < 0.05). These results
      suggest that HTR3B is involved in the development of TRS in the Japanese
      population.

PMID- 18807292
TI  - Relation of falls efficacy scale (FES) to quality of life among nursing home
      female residents with comparatively intact cognitive function in Japan.
AB  - The purpose of this study was to investigate the relation of the Falls Efficacy
      Scale (FES) to quality of life (QOL) among nursing home residents. The subjects
      were 133 institutionalized women aged 70 years or older. They had comparatively
      intact cognitive function, with a Mini-Mental State Examination (MMSE) score of
      15 or more, and could provide sufficient informed consent for a questionnaire
      survey. We evaluated their age, height, weight, body-mass index, history of hip
      fracture, history of fall(s) within the past year, complicating conditions, MMSE,
      Medical Outcomes Study 8-Item Short-Form Health Survey (SF-8), FES, and their
      subscores for Functional Independence Measure (FIM) motor items (self care,
      sphincter control, transfer, locomotion). There was a significant relationship
      between the Physical Component Summary (PCS) of SF-8 and FES. In each subscale,
      FES showed significant relations that were especially close in physical
      functioning (PF) and role physical (RP), with those relations proving stronger
      than those of the subscores of transfer and locomotion. In conclusion, the
      present results suggested that taking account of mental confidence is important
      for physical QOL, and that falls self-efficacy, including not only physical
      activity per se but also mental confidence, should be given prominence in the
      physical QOL of the institutionalized elderly.

PMID- 18807293
TI  - Long-term outcome and prognostic factors for yolk sac tumor of the ovary.
AB  - Yolk sac tumors of the ovary (YST) are rare and highly malignant tumors occurring
      in children and young adults. Because of its rarity, YST prognostic factors
      remain unclear. Our purpose was to evaluate the prognostic factors in YST. We
      performed a retrospective review of 36 patients with pure YST from 1986 to 2006.
      The 5-year overall survival and progression-free survival were 66.6% and 68.8%,
      respectively. Patients with stage I-II disease had a more favorable prognosis
      than those with stage III-IV (p < 0.05). Those with an ascites volume of less
      than 100 ml or a residual tumor measuring less than 1 cm had improved to a
      relatively good prognosis. Neither serum AFP level nor age had any significant
      correlation with the prognosis in this study. In conclusion, the FIGO
      (International Federation of Gynecology and Obstetrics) stage, ascites volume and
      residual tumor size tended to affect the prognosis of YST.

PMID- 18807294
TI  - Mucinous cystadenoma of the appendix associated with muscular and neuromatous
      hyperplasia: report of a case.
AB  - Mucinous cystadenoma of the appendix is a type of appendiceal mucocele and a
      rather rare condition usually found incidentally in the course of other abdominal
      surgery. A previous evaluation of 73 appendiceal mucoceles showed that this
      disease was often associated with adenocarcinoma and other epithelial atypia.
      This observation suggested that patients with mucinous cystadenoma of the
      appendix also have some underlying disorders. However, non-epithelial changes
      associated with appendiceal mucocele have not been reported so far. In this
      study, we presented for the first time a mucinous cystadenoma of the appendix
      associated with muscular and neuromatous hyperplasia.

PMID- 18807295
TI  - Specialist hospitalists: could they be the answer to the challenge of call
      panels?
AB  - Having your hospital hire specialist hospitalists can provide much-needed relief
      for EDs that can't fill their call panels. However, be aware of the limitations
      of such a strategy: Only specialties that are needed on a regular basis, i.e.,
      general surgeons or orthopedists, will make economic sense. There may be some
      patient resistance to unfamiliar physicians in sensitive areas such as obstetrics
      and gynecology. A surgical hospitalist may not have the intimate knowledge of a
      patient that their regular surgeon would have.

PMID- 18807296
TI  - Disaster surge fails to fluster ED staff.
AB  - Advance preparation can make a big difference in how your department responds to
      emergencies, as demonstrated by the ED at Caritas Norwood (MA) Hospital in the
      wake of a recent train wreck. Here are some actions taken in advance that help
      facilitate a successful response: Their disaster plan included the immediate
      availability of nurses who were working on other floors. A day surgery area had
      been designated to handle patient overflow and provided 20 additional beds. A
      designated conference room for family members helped make them comfortable while
      keeping them out of the hectic ED area.

PMID- 18807297
TI  - Award-winning program slashes sepsis mortalities.
AB  - ED leaders at Christiana Care Health Services of Wilmington, DE, say a successful
      sepsis treatment program should bring the same urgency and attention to detailed
      protocols as you would to victims of heart attack or stroke. Such an approach
      enabled them to reduce the mortality rate for patients with severe sepsis from
      61.7% to 30.2%. Educate your nurses and physicians to recognize the main SIRS
      (Systemic Inflammatory Response Syndrome) criteria. Standardized care will lead
      to earlier, more effective treatment and help eliminate potential complications.
      The term "golden hour" should not be limited to stroke and myocardial infarction
      victims. Create a sense of time urgency in your staff.

PMID- 18807298
TI  - Competitive concerns bring PAs, NPs into triage area.
AB  - The ED at Harborview Medical Center in Seattle has proven new competition doesn't
      have to mean a loss of business or staff members. They moved physician assistants
      (PAs) and nurse practitioners (NPs) into triage to compete with urgent care
      clinics. When you have a hard time attracting midlevel practitioners, examine the
      local market to see who is recruiting them. Create a small, separate area in
      triage where midlevel practitioners can treat patients with less serious
      conditions. Be flexible with the number of hours the PAs and NPs work. Be
      prepared to expand their hours as demand increases.

PMID- 18807299
TI  - New psych unit eases patient burden in ED.
AB  - Creating a special unit for psychiatric patients frees up beds in your ED,
      ensures better care for that patient population, and improves the atmosphere in
      the main department for the rest of your patients. Consider these suggestions:
      The creation of a psych unit can be extremely costly. Be prepared to demonstrate
      projected savings when pitching the idea to administration. Make sure an ED
      physician has overall responsibility for each patient at all times. Keep a
      regular group of nurses in rotation. This setup will help ensure smooth handoffs.

PMID- 18807300
TI  - 'Mock EDs' help finalize design plans.
AB  - Nurse managers involved in the planning for two new EDs in the Fort Lauderdale,
      FL-based Broward Health system provided invaluable input to the design team which
      should enhance patient safety by ensuring efficient and speedy care. Here are
      their suggestions for other nurse managers who are planning similar projects:
      Ensure that supplies and equipment are readily accessible to the providers who
      will use them. If you allow family members in patients' rooms, be sure to leave
      enough space for a stretcher and for family. Make sure storage space is ample and
      that there are an adequate number of electrical outlets.

PMID- 18807301
TI  - Audit of provincial gastroenterology services in the Western Cape.
AB  - BACKGROUND: While disorders such as gastro-oesophageal reflux disease,
      gastrointestinal (GI) cancers and inflammatory bowel disease are prevalent among
      all racial groups in the Western Cape, there is little knowledge of local GI
      service provision. The state of equipment, facilities and staffing is largely
      unrecorded and to date unknown. The aim of this study was to audit the
      availability of GI facilities in the provincial sector, which provides care for
      the majority of people in the Western Cape. METHOD: All hospitals in the Western
      Cape providing endoscopy were evaluated by means of a hands-on audit, to identify
      available organisational infrastructure. Data including staffing, details and
      utilisation of existing equipment, maintenance and disinfection techniques and
      delays in service provision were collected. RESULTS: Over a period of 12 months,
      17 Western Cape hospitals were visited: 3 tertiary, 5 regional and 9 district
      level institutions. There are currently 89 GI endoscopes in state service, with
      an average age of 6.1 years (range 1-23 years). While most institutions utilise
      video endoscopy, in many instances equipment is near the end of its economic
      life. A total of 26,434 endoscopic procedures were performed over a 12-month
      period. Overall at least 60% of all adult endoscopy was undertaken at tertiary
      institutions. The mean delay from consultation until gastroscopy or colonoscopy
      was 9.25 weeks (range 0.5-28 weeks) and 8 weeks (range 1-20 weeks), respectively.
      Only 1 tertiary and 1 regional hospital employed fully trained, registered
      nurses, and the majority of institutions did not conform to internationally
      accepted standards for the maintenance and disinfection of endoscopic equipment.
      CONCLUSION: While endoscopy equipment is widely distributed throughout the
      province, it is evident from this study that services in the Western Cape fall
      short of international standards, with delays in endoscopic provision, lack of
      adequate equipment, inadequate scope maintenance and disinfection and a shortage
      of trained staff. As such, much of the population reliant on state facilities has
      poor access to GI health care. These deficiencies need to be addressed.

PMID- 18807302
TI  - Audit of appendicectomies at Frere Hospital, Eastern Cape.
AB  - OBJECTIVE: We sought to evaluate the surgical service in the central part of the
      Eastern Cape Province by reviewing the practice of appendicectomy at Frere
      Hospital. Specifically, it was our aim to compare the service to those patients
      who reside in and outside the East London metropolitan area and the outcomes of
      patients according to their operative finding. PATIENTS AND METHODS: A
      retrospective study was performed on the medical records of all patients who
      underwent appendicectomy in a 26-month period. This entailed a thorough review of
      demographic factors, mode of presentation, operation factors and findings, and
      the postoperative course. RESULTS: . In the study period, 436 appendicectomies
      were performed, of which 81% were performed after hours, with a consultant
      surgeon present in only 6% of cases. Of the group, 51% had a perforated appendix
      at surgery, and 12% a normal appendix. There was a significantly increased risk
      of perforation at the extremes of age and in patients from outside East London
      (63% v. 35% in East London). Those with perforated appendices stayed an average
      of 7.3 days in hospital, compared with 5 days for those with earlier
      appendicitis. Of the perforated group, 21% developed a complication, with 86% of
      all complications occurring in this group. The hospital stays were longer in
      those perforated appendices that were drained (10.7 days v. 6.1 days), and the
      rate of complications higher in this subgroup. Four patients died (1%)--all in
      the perforated group. DISCUSSION: The perforation rate in our setting is
      significantly higher than other published results. Patients with perforated
      appendices have longer hospital stays and are more likely to develop significant
      complications, including re-operation. Patients from outside East London, males
      and those at the extremes of age are more likely to have perforated appendices.
      This study lends little support to the advocates of drains, and recommends the
      use of non-absorbable sutures for skin closure. The majority of procedures are
      performed after hours by medical officers and registrars, but there is no
      evidence to suggest that this practice be altered, particularly in light of the
      high perforation rate. The main factor identified as contributing to the huge
      discrepancy between perforation rates (and hence morbidity) is delay in
      presentation to the operating surgeon for the region. Patient factors may
      contribute, but service factors are regarded as significant, including poor
      access to clinics and hospitals, transport and ambulance services, and the
      expertise of the referring medical staff. The need to improve the quality of
      patient care in the under-serviced rural areas of the Eastern Cape is
      highlighted.

PMID- 18807303
TI  - Why is surgery cancelled? A retrospective evaluation.
AB  - INTRODUCTION: The cancellation of surgery wastes theatre time and creates
      hardship for patients, who often plan their working and family lives around the
      proposed operation date. METHODS: A retrospective evaluation of cancellations of
      scheduled elective and urgent operations was done using theatre records from May
      2006 to April 2007. The reasons for cancellation were examined. RESULTS: Of a
      total of 5,786 operations, 5.6% were cancelled or postponed. Lack of medical
      clearance and patient preparation (65.1%) was the most common reason for
      cancellation. Lack or failure of instruments and patient cancellation constituted
      2.8% and 1.8% of the cancellations respectively. CONCLUSION: Last-minute
      cancellation of surgery was a significant problem, and appreciation of the usual
      reasons for cancellations can improve theatre utilisation and avoid
      inconveniencing patients and their families.

PMID- 18807304
TI  - Acute pancreatitis: demographics, aetiological factors and outcomes in a regional
      hospital in South Africa.
AB  - INTRODUCTION: The spectrum of aetiologies and outcomes of acute pancreatitis in
      South African settings is under-reported. We report our experience at a regional
      hospital and compare it with international norms. PATIENTS AND METHODS: Data were
      prospectively collected on all admissions of patients with acute pancreatitis to
      a regional hospital during the period June 2001-April 2006. The causes of the
      pancreatitis were noted and complications and mortality rate were determined.
      RESULTS: From June 2001 to April 2006 there were 322 admissions of 282 patients
      with acute pancreatitis. The median age was 37 years (range 13-73 years). There
      were 94 females and 188 males. Episodes of pancreatitis were associated with
      alcohol consumption in 62% of cases and with gallstones in 14%; 4% of cases were
      associated with both gallstones and alcohol consumption, 8% with dyslipidaemia
      and 5% with retroviral disease. In 15% of admissions local complications
      developed, and 9% of admissions ended in death of the patient. Of the 28 deaths,
      71% occurred in the first 2 weeks. CONCLUSIONS: As in other South African
      reports, alcohol was the main cause of pancreatitis. Outcomes in this series are
      similar to those in Western studies except that the majority of deaths occurred
      early, implying that improved supportive care may improve overall survival.

PMID- 18807305
TI  - Acinar cell carcinoma--a rare tumour of the pancreas.

PMID- 18807306
TI  - Clinical and pathological features of hereditary mixed polyposis syndrome: report
      on a South African family.
AB  - BACKGROUND: Hereditary mixed polyposis syndrome is characterised by multiple
      large-bowel polyps of differing histological types including a mixture of
      atypical juvenile polyps, hyperplastic polyps and adenomas. Affected individuals
      are thought to have an increased risk of malignancy, possibly via the juvenile
      polyposis pathway. METHODS: A 51-year-old woman (with a history of a colectomy
      for polyps during childhood) presented with rectal bleeding. Endoscopy
      demonstrated small rectal polyps which were hyperplastic on histology. A family
      tree was drawn up and the three children of the proband underwent flexible
      sigmoidoscopy. RESULTS: Endoscopic surveillance of the three children revealed
      one who had a similar phenotype to the mother. This child underwent colectomy and
      ileorectal anastomosis. The pathological specimen revealed more than 70 polyps,
      with a combination of juvenile retention, hyperplastic, adenomatous and
      inflammatory polyps. A second child had multiple small hyperplastic polyps, and
      the third had a normal colon. Although the gene locus for the disorder has been
      mapped, neither the gene nor the disease-causing mutation has been defined.
      CONCLUSION: A rare inherited polyposis syndrome has been identified in a South
      African family. Where clinical suspicion of a possible inherited condition
      exists, investigating at-risk first-degree relatives confirms the inherited
      nature of the disease. It is possible to use genetic haplotyping (i.e. with a
      range of markers in the area of the gene) to provide statistical risk to
      immediate relatives and therefore those at highest risk.

PMID- 18807307
TI  - Oesophago-pleuro-cutaneous fistula in an HIV-positive patient.

PMID- 18807308
TI  - Substance abuse among medical students and doctors: a call for action.

PMID- 18807309
TI  - Organ transplantation in India: problems and solutions.

PMID- 18807310
TI  - Editorial policy and the reporting of randomized controlled trials: a survey of
      instructions for authors and assessment of trial reports in Indian medical
      journals (2004-05).
AB  - BACKGROUND: Many international journals require authors of randomized controlled
      trials to adhere to standards of reporting described in the statement of the
      Consolidated Standards of Reporting Trials (CONSORT) and the requirements issued
      by the International Committee of Medical Journal Editors (ICMJE). We examined
      the extent to which these international standards have been adopted by Indian
      medical journals. METHODS: To identify Indian medical journals that publish
      randomized controlled trials, we did electronic searches of the websites of the
      National Informatics Centre (Indian Medlars Centre), Database of Open Access
      Journals, National Library of Medicine, WHO's Index Medicus for the South-East
      Asian region and Google. We analysed their instructions to authors for
      endorsement of the CONSORT statement and the ICMJE requirements for reporting of
      randomized controlled trials. We then identified all randomized controlled trials
      published in these journals during 2004 and 2005 and assessed them against
      selected CONSORT items and ICMJE requirements, and scored them on the Jadad
      scale. RESULTS: Of the 65 journals selected, 38 (58.5%) mentioned the ICMJE
      requirements in their instructions for authors but only 20 (31%) specifically
      required authors to submit manuscripts in accordance with the CONSORT statement.
      Of 151 randomized controlled trials published during 2004-05, only 4 of 13
      (30.8%) selected CONSORT items were reported in > 50% of trial reports. Items
      reflecting internal validity were poorly reported. Jadad scores were
      significantly higher for general medical journals compared with specialty
      journals (mean difference 0.46; 95% CI: 0.15-0.78; p = 0.005) and in trials
      published in 2005 over those published in 2004 (mean difference 0.48; 95% CI:
      0.18-0.79; p = 0.002). Ethical issues were poorly reported in one-third of
      reports, and sources of funding and conflicts of interest were not declared in
      over three-fourths. Adequacy of reporting was not related to endorsing either the
      CONSORT statement or the ICMJE requirements. CONCLUSION: Medical journals
      published in India should adopt internationally recognized norms for reporting
      clinical trials and work with authors, reviewers and institutional review boards
      to improve the standards of conduct, reporting and validity of inferences of
      trials.

PMID- 18807311
TI  - Ultrasound evaluation of thyroid size: a large nationwide study of schoolchildren
      in India.
AB  - BACKGROUND: Ultrasound assessment of thyroid volume is considered a more
      objective method than clinical palpation for the diagnosis of goitre. We used
      ultrasonography to establish normal reference cut-off points of thyroid volume in
      schoolchildren of different socioecomonic groups in India and compared the
      results with international norms. METHODS: In a cross-sectional study, we
      clinically examined 27,250 children from the lower and higher socioeconomic
      strata (SES) from all over India to determine their goitre staging. A single
      sonologist, using ultrasonography, assessed the thyroid volume in a subset of
      15,986 children (8463 from the lower and 7523 from the higher SES). Students were
      recruited from at least one school each representing the higher and the lower
      SES, from cities located in 5 zones of India. Children with known thyroid
      disorders were excluded from the study. RESULTS: Clinical evaluation revealed a
      mean goitre prevalence of 19.9% (23.2% in girls; 16.5% in boys; 17.1% in the
      higher SES; 23.5% in the lower SES). The thyroid volume as assessed by
      ultrasonography was significantly higher in children from the lower SES (mean
      5.65 ml, SE 0.02) compared with those from the higher SES (mean 5.02 ml, SE 0.02)
      after adjusting for the imbalance in body surface area (p < 0.001). Using
      international norms (WHO 2004), the prevalence of goitre in various body surface
      area categories among children who had no goitre on clinical examination ranged
      from 48.2% to 75.1% for boys and 23.2% to 67.4% for girls. CONCLUSION: The
      striking discrepancy in the prevalence of goitre assessed by using clinical
      examination and ultrasound techniques suggests that the norms recommended by WHO
      based on ultrasound techniques are not appropriate for India.

PMID- 18807312
TI  - Substance use among medical students: time to reignite the debate?
AB  - BACKGROUND: Substance use among medical students could impact on the conduct,
      safety and efficiency of future doctors. Despite serious medicolegal, ethical and
      political ramifications, there is little research on the subject, especially from
      the Indian subcontinent. We aimed to explore the patterns of substance use among
      a sample of medical students from the Indian subcontinent. METHODS: An
      opportunistic, cross-sectional survey of medical students from 76 medical schools
      attending an inter-medical school festival. A brief self-reported questionnaire
      was used to identify current and lifetime use of tobacco, alcohol, cannabis,
      heroin and non-prescription drugs. Multivariable logistic regression analysis was
      used to identify factors associated with illicit substance use. RESULTS:
      Responses from 2135 medical students were analysed. Current alcohol and tobacco
      (chewable or smoked) use was reported by 7.1% and 6.1% of the respondents,
      respectively. Lifetime use of illicit substances was reported by 143 (6.7%)
      respondents. Use of illicit substances was strongly associated with use of
      tobacco, alcohol and non-prescription drugs. CONCLUSION: This study provides a
      snapshot of the problem of substance use among medical students from the Indian
      subcontinent. The reported prevalence of alcohol and illicit substance use in our
      sample was lower, while tobacco use was similar, when compared with data from
      western studies. Further research is needed from the Indian subcontinent to study
      nationwide patterns of substance use among medical students, and to identify
      important determinants and reinforce protective factors. Strategies need to be
      developed for supporting students with a substance use problem.

PMID- 18807313
TI  - Turning our backs on rheumatic fever.

PMID- 18807314
TI  - Childhood body mass index: a predictor of adult coronary heart disease?

PMID- 18807315
TI  - Dietary carbohydrates and risk of type 2 diabetes: are rice eaters doomed?

PMID- 18807316
TI  - The kidney and the eye in people with diabetes mellitus.

PMID- 18807317
TI  - A good death: a matter of concern in India.

PMID- 18807318
TI  - Medical education in India: a student's perspective.

PMID- 18807319
TI  - The bane of public sector medical colleges and their hospitals.

PMID- 18807320
TI  - Strike by health workers: a violation of medicine's social contract.

PMID- 18807321
TI  - The need to regulate and evaluate laboratory diagnostic tests in India: a measure
      long overdue.

PMID- 18807322
TI  - Office publications.

PMID- 18807323
TI  - A multifaceted approach to increase access to oral health care one step at a
      time.

PMID- 18807324
TI  - Digital radiography in pediatric and special care dentistry.

PMID- 18807325
TI  - Understanding xerostomia.

PMID- 18807326
TI  - Is the grass greener on the other side of the fence?

PMID- 18807327
TI  - Achieving process control and efficiency through training objectives.

PMID- 18807328
TI  - [Palliative care in a psychiatric-somatic care unit].
AB  - Patients with severe psychiatric and somatic disorders may require admission to a
      combined psychiatric-somatic care unit. These units provide specialised
      psychiatric and somatic care as well as palliative care. This is illustrated by
      two case reports. A 51-year-old man with a malignant brain tumour was admitted to
      our psychiatric-somatic care unit after threatening his wife and children. He was
      aggressive and confused. Seizures were suspected and palliative care was needed.
      Within a few weeks his condition deteriorated. He died 1 day after terminal
      sedation had been initiated. A 78-year-old woman was admitted to receive daily
      electroconvulsive treatment (ECT) for depression with catatonia. The ECT had to
      be interrupted repeatedly due to comorbid infections and complications. She died
      3 days after palliative care was initiated.

PMID- 18807329
TI  - [Prolonged effect of intra-articularly administered corticosteroids in
      combination with arthroscopic lavage in patients with an inflammatory arthritis
      of the knee].
AB  - Arthroscopic lavage of a joint with saline followed by the administration of
      corticosteroids intra-articularly could lead to an improved functioning of the
      joint. In a recent study published in this issue the results of arthrocentesis
      with intra-articular administration of corticosteroids was compared with lavage
      with or without intra-articular administration of corticosteroids in patients
      with a non-infectious inflammatory arthritis of the knee joint. The results
      confirm earlier reports, which demonstrated that the beneficial therapeutic
      effects of corticosteroids administered intra-articularly can be prolonged by a
      therapeutic lavage in patients with non-infectious inflammatory arthritis,
      provided the lavage is performed with a sufficient amount of saline.

PMID- 18807330
TI  - [Local treatment for persistent inflammatory arthritis of the knee: intra
      articular injection of glucocorticoids and bed rest].
AB  - Two studies evaluating treatment options for persistent mono-arthritis are
      discussed. In one study arthroscopic lavage plus intra-articular glucocorticoids
      was compared with arthroscopic lavage without glucocorticoids, and with joint
      aspiration plus glucocorticoids. Both intra-articular glucocorticoids and lavage
      have their merits, but glucocorticoids appear to be slightly more effective. In
      the second study radioactive Yttrium plus intra-articular glucocorticoids was
      compared with glucocorticoids alone. Yttrium provided little additional value.
      There are some indications that a period of strict bed rest after treatment is
      beneficial. Intra-articular glucocorticoids should not be administered more
      frequently than three times per year in the same joint.

PMID- 18807331
TI  - [Needlestick injuries and unprotected sex in the Netherlands].
AB  - Needlestick accidents can be divided into occupational and non-occupational
      accidents. In the Netherlands, occupational accidents are often managed
      adequately on-site, but the management of non-occupational accidents can be
      improved. It is questionable whether prophylaxis after unprotected sex (voluntary
      and involuntary) should be managed using current needle-stick protocols. These
      accidents require a separate protocol.

PMID- 18807332
TI  - [Hysteroscopy: useful in diagnosis and surgical treatment of intrauterine
      lesions].
AB  - Hysteroscopic surgery has an established role in the field of gynaecologic
      surgery. With the introduction of thinner scopes and simpler instruments part of
      the interventions can now be performed on an outpatient basis. Hysteroscopy can
      be used for the removal of polyps and myomas, endometrial resection,
      synechiolysis, sterilisation, septum resection and the removal of remnants from
      pregnancy. Hysteroscopic surgery can be an option for patients who wish to
      preserve the uterus and for the treatment of infertility. The complication rate
      associated with hysteroscopic interventions is low. The most common events are
      intravasation of distension fluid, uterine perforation, and haemorrhage. The
      complication rate depends on the complexity of the procedure.

PMID- 18807333
TI  - [Guideline 'Needlestick injuries': risk assessment and post-exposure management
      in practice].
AB  - Guideline 'Needle stick injuries': risk assessment and post-exposure management
      in practice The objective of the national guideline 'Needle stick injuries' is to
      make the assessment of needle stick injuries more structured and uniform. The
      injury is classified as high risk or low risk according to the volume of blood
      transmitted. For high-risk injuries measures to prevent hepatitis B, hepatitis C
      and HIV infection have to be considered, whereas for low-risk injuries only
      measures to prevent hepatitis B. The need for post-exposure prophylaxis is
      determined by the victim's immunity to hepatitis B and the presence of hepatitis
      B virus, hepatitis C virus or HIV in the source person. Post-exposure prophylaxis
      against hepatitis B consists primarily of hepatitis B vaccination; hepatitis B
      immunoglobulin is added in the case of a high-risk injury with a hepatitis B
      positive source or a source belonging to a risk group for hepatitis B. In high
      risk injuries the victim is tested for hepatitis C and HIV transmission (except
      in case of a seronegative source). Antiretroviral postexposure prophylaxis is
      advised for high-risk injuries with a HIV seropositive source or a source
      belonging to a risk group for HIV.

PMID- 18807334
TI  - [Diagnostic image (388). A boy with blue ears].
AB  - An 8-year-old boy was presented with painful blue ears due to infection with
      Mycoplasma pneumoniae. The changes disappeared spontaneously.

PMID- 18807335
TI  - [Arthroscopic lavage plus corticosteroids is more effective than joint aspiration
      plus corticosteroids in patients with arthritis of the knee].
AB  - OBJECTIVE: To compare the efficacy of arthroscopic lavage plus corticosteroids
      (ALC), arthroscopic lavage plus placebo (ALP), and joint aspiration plus
      corticosteroids (JAC) in patients with arthritis of the knee, and to identify
      clinical or histological factors that predict outcome. DESIGN: Prospective,
      randomised. METHOD: Patients with arthritis of the knee (not due to gout,
      osteoarthritis or septic arthritis) were randomised to 1 of 3 treatment arms:
      ALC, ALP or JAC. The primary endpoint was time to recurrence; recurrence was
      defined as recurrent or persistent symptomatic knee swelling requiring local
      treatment, and/or non-improvement in knee joint score. Synovial tissue specimens
      were collected for histological analysis. RESULTS: Of the 78 patients enrolled, 3
      did not receive the intended therapy and 3 were lost to follow-up. The median
      time to recurrence was 9.6 months in the ALC group, 3.0 months in the JAC group
      and 1.0 month in the ALP group. Compared with ALC, the relative risk of
      recurrence of arthritis (RR) was 2.2 for JAC (95% CI: 1.2-4.2; p = 0.02) and 4.7
      for ALP (95% CI: 2.3-9.4; p < 0.0001). In the ALC group, extensive synovial
      fibrosis was associated with a higher risk of recurrence (RR 5-7; 95% CI: 1.6
      20.5; p < 0.01). CONCLUSION: Arthroscopic lavage plus corticosteroids was more
      effective than arthroscopic lavage plus placebo or joint aspiration plus
      corticosteroids. The absence of synovial fibrosis predicted a beneficial
      response.

PMID- 18807336
TI  - [Inadequate infrastructure for follow-up after needlestick injuries in the
      Netherlands].
AB  - OBJECTIVE: To determine how needle-stick injuries are dealt with in the
      Netherlands. DESIGN: Study using questionnaires. METHOD: In order to study
      whether victims of needle-stick injuries have access to proper treatment, we sent
      questionnaires to hospitals (n = 103) and Municipal Health Services (MHS) (n =
      36) in the Netherlands. We enquired after the possibilities of risk-estimation
      and follow-up, the performance of necessary laboratory tests, direct
      administration of preventive medication and backup facilities. RESULTS:
      Questionnaires were returned by 113 (81%) institutions. 74% of the hospitals and
      71% of the MHS provided follow-up for needle-stick injuries from outside their
      own institution. Necessary laboratory tests were not always available or
      sometimes could not be performed on an immediate basis. In addition, essential
      medication was not always directly available. MHS recognized the advantage of
      cooperation during followup of needle-stick injuries more than hospitals.
      CONCLUSION: Based on the results there is no guarantee that victims of needle
      stick injuries in the Netherlands have access to appropriate care at any location
      in the Netherlands on a 24/7 basis. We recommend improvement of the
      infrastructure and cooperation between health care organizations to guarantee
      improved follow-up in every region.

PMID- 18807337
TI  - [Intermittent flank pain].
AB  - Flank pain is a common problem that can be caused by a variety of abnormalities.
      In this case report we describe two patients with intermittent flank pain with an
      unusual cause: intermittent ureteropelvic junction obstruction due to crossing of
      accessory renal vessels. Instant imaging at the time when the symptoms occur
      seems the best way to prevent delays in diagnosis and treatment.

PMID- 18807338
TI  - [Fewer caesarean sections for breech presentation following external cephalic
      version according to a protocol in a special office visit].

PMID- 18807339
TI  - [Quality assurance in medical assessments].

PMID- 18807340
TI  - [Decision analysis--a novel approach for calculating the cost-efficiency of
      medical tests].
AB  - Before issuing an insurance policy (e.g. life, disability, critical illness),
      insurers will usually carry out a medical risk assessment in order to prevent
      adverse selection. Often, the health questions in the application form will not
      be sufficient for this purpose since most applicants are not well-versed in
      medical science and terminology. If the insurer needs additional medical
      information such as a private medical attendant's report or current laboratory
      tests, however, costs will be incurred, which usually have to be paid by the
      insurer. What is the minimum sum insured which makes it worthwhile for the
      insurer to conduct certain screening tests, for example? Both the costs of
      medical screening and the associated savings are difficult to measure and involve
      a variety of different factors. Moreover, most parameters can only be estimated
      with limited accuracy. Therefore, we have developed a new calculation model using
      a decision-analysis approach. The new model makes it possible to analyse complex
      situations while taking into account the uncertainty of parameter estimation. Our
      findings show that in Germany, for instance, current sum thresholds for older
      applicants could in many cases be lowered and would still be cost-effective.

PMID- 18807341
TI  - [Treatment options for cartilage damage in the knee joint].
AB  - The complex structure of articular cartilage is essential for understanding
      biology and function. Despite performing with a relatively low metabolic
      activity, healthy articular cartilage has amazing capacity to sustain itself and
      carry out its function. Chondrocytes are active in maintaining the tissue's
      matrix, showing differences in the anatomic structure. Articular cartilage has
      extraordinary mechanical properties and lasting durability. It is only a few
      millimetres thick. The cartilage wears resistance while bearing large loads
      throughout a person's lifetime. Otherwise we see cartilage destructions in young
      patients without a trauma. It is important to know that the articular cartilage
      decreases with age. The ability of the MRI to obtain reproducible, accurate
      images of cartilage has enabled early detection of cartilage lesions and provides
      clinically relevant information when planning cartilage repair. MRI depicts the
      subchondral bone and all other anatomic structures of the knee. This information
      is vital when planning for complex techniques that require careful size
      delineation of the cartilage lesion and evaluation of the surrounding subchondral
      bone. In addition to aiding in preoperative planning, the MRI offer an important
      objective evaluation of cartilage repair to be correlated with the more
      subjective clinical outcome instruments and provide insight into the biology of
      the repair process. The repair strategies are currently available for clinical
      use when treating articular cartilage lesions. These strategies fall into one of
      the following categories: 1. Palliative-conservative treatment (local or systemic
      application), 2. Intrinsic-repair enhancement/marrow stimulation (drilling,
      microfracture, arthroplasty), 3. Cell-based repair (collagen associated
      chondrocyte transplantation or microfracture with collagen). The use of
      biodegradable scaffolds can be used either alone or as delivery vehicles for
      growths factors. This technique could be a new way for winning structurally and
      biomechanically appropriate tissue.

PMID- 18807342
TI  - [Off-label use of drug-eluting coronary stents].
AB  - Current recommendations of the German Cardiac Society on percutaneous coronary
      interventions (PCI) summarise the database available for the use of drug-eluting
      stents (DES) for the treatment of symptomatic coronary artery stenoses. This
      analysis concludes that the safety and efficacy of drug-eluting stent platforms
      have been shown in on- and off-label situations. However, stenting with DES
      should be critically examined and evaluated in each patient. The decision to use
      a DES depends on the analysis of the individual morbidity, history of cardio
      vascular disease and the specific coronary morphology. Patients characterised by
      a high risk of restenosis following PCI benefit in particular from DES use. In
      these cases, the off-label implantation of DES is indicated and necessary.

PMID- 18807343
TI  - [Integrative treatment in psychiatric hospitals brings long-term improvements to
      local outpatient treatment structures].
AB  - In the future, a range of outpatient solutions with services provided by
      different partners will have to be developed for highly complex psychiatric
      cases. The programme expenses will be covered by different institutions. Taking
      the example of the Department of Addiction and Psychotherapy of the Rhine state
      hospital in Bonn, three integrative projects are presented, which have had a
      secondary, lasting effect on local outpatient treatment structures. Besides the
      excellent clinical cooperation between the different institutions involved, an
      important element of all three projects has been the intensive cooperation
      between all three sponsors. For the future, it will be necessary to create
      financial incentives for the participants in addition to promoting integrative
      approaches. Much creative management is also needed on the part of the
      psychiatric hospital in order to fulfil its role as a centre of competence for
      psychiatric problems.

PMID- 18807344
TI  - [Analysis of sports injuries covered by German occupational accident insurance
      associations at a former district hospital over a period of six years].
AB  - An epidemiological analysis was carried out of 1,126 sports injuries covered by
      German occupational accident insurance at a small regional hospital over a period
      of six years, of which 86.6% were allotted to the sport at schools. The types of
      sport most frequently involved were general fitness sports (n = 486), soccer (n =
      137), volleyball (n = 126), gymnastics (n = 125) and basketball (n = 121). In the
      general fitness sports (n = 228 women/girls, n = 258 men/boys), bruising injuries
      dominated (47%), followed by sprains (29%), mostly involving the upper
      extremities (53%). In soccer injuries (proportion of woman = 15%), bruising and
      injuries to the lower extremities ranked first. Falls (33%) and sprains (31%)
      were the most common gymnastics injuries. Injuries to the upper extremities were
      most common in volleyball and basketball with 72% and 68% respectively. The
      distribution of these sports injuries more or less mirrors the distribution of
      sports disciplines at schools and institutions like the Federal Border Police.
      Sporting activity here should include preventive elements such a proprioceptive
      training.

PMID- 18807345
TI  - ["Anecdotal evidence" instead of evidence? Critical comments on
      Electroacupuncture in Full (EAV)].

PMID- 18807346
TI  - [Sanatoriums in disguise---treatment in an Alpine Clinic].

PMID- 18807347
TI  - [Comment on: Evidence and medical decision-making--what kind of evidence do we
      really need? in Versicherungsmedizin 59 (2007) Heft 4 S. 166]].

PMID- 18807348
TI  - Keeping track. AAMIC, institute ready online guides to centers' conflict-of
      interest policies.

PMID- 18807349
TI  - Selling solutions. Frustrations help inspire doctors' products.

PMID- 18807350
TI  - When the wind blows ... Dems, GOP don't seem anxious to tackle healthcare, so the
      people must speak up.

PMID- 18807351
TI  - A guide, not a leash. Don't let evidence-based medicine shackle good caregivers.

PMID- 18807352
TI  - Maximizing value. RHIOs help you get more out of electronic records.

PMID- 18807354
TI  - Getting up to speed. With FCC's help, states, regions forming networks.

PMID- 18807353
TI  - Putting their money where the money is. The U.S. healthcare sector draws plenty
      of foreign direct investment. But not providers. Could universal coverage change
      that?

PMID- 18807355
TI  - A brief history of: sports medicine.

PMID- 18807356
TI  - The truth about teen girls. So you think they're having set too soon and its the
      media's fault. It's not that simple.

PMID- 18807357
TI  - From health to wealth. Investing in healthy living now may add up to hundreds of
      thousands of dollars later in life.

PMID- 18807358
TI  - A theory of evolution--step by step: how women are changing the workforce.

PMID- 18807359
TI  - Identification and evaluation of Missouri's children with autism spectrum
      disorders: promoting a rapid response.

PMID- 18807360
TI  - Therapeutic interventions in autism: a review for primary care physicians.
AB  - Autism spectrum disorders are characterized by impairments in social interaction,
      communication, and repetitive and stereotyped interests with onset in infancy.
      Early identification allows the possibility of early intervention, for the
      ultimate purpose of optimizing quality of life and functional independence. Early
      implementation of educational interventions are a core component of treatment,
      along with management of medical comorbidities and psychopharmacology, which we
      will review. Alternative therapies are frequently utilized, of which the
      clinician needs to be aware.

PMID- 18807361
TI  - Hulshof for governor?

PMID- 18807362
TI  - Neurosurgery in the 21st century: The role of intraoperative imaging during
      neurosurgery for neuro-oncology and neuro-vascular disease.

PMID- 18807363
TI  - Traumatic brain injury in children.
AB  - Traumatic brain injury (TBI) is the most common cause of death and disability
      among children and young adults. TBI consists of both primary injury and a
      secondary injury resulting from hypoxia, arterial hypotension, and elevated
      intracranial pressure. Improved outcomes from pediatric TBI have resulted from
      improved primary recognition and treatment strategies. Treatment and assessment
      aimed specifically toward the immature brain can improve both functional outcome
      and long-term psychosocial impairment.

PMID- 18807364
TI  - Modern management of brain aneurysms and vascular malformations.
AB  - The management of brain aneurysms and vascular malformations has evolved rapidly
      in recent years. More of these lesions are being diagnosed due to higher fidelity
      imaging, treatment has become more refined and often less invasive, and patients
      have become more integrated in their own care due to advances in
      informationtechnology. This article reviews the clinical characteristics and
      therapeutic options for patients harboring these lesions, with a particular focus
      on recent advances in the field.

PMID- 18807365
TI  - Diagnoses in epilepsy commonly treated with surgery.
AB  - The term epilepsy embraces a constellation of syndromes, each manifesting with
      recurrent episodic seizures. Uncontrolled epilepsy carries a significant medical
      morbidity, reduction in quality of life, and a notable increased mortality. A
      certain percentage of patients are candidates for surgical treatment, which can
      be one of the most effective long term options for seizure cure. The diagnoses
      amenable to surgery and their outcomes are reviewed.

PMID- 18807366
TI  - Deep brain stimulation: current and emerging indications.
AB  - Deep brain stimulation (DBS) has been used to treat a number of neurological and
      psychiatric diseases. Initially applied to chronic pain, DBS today is routinely
      used to treat movement disorders, predominantly Parkinson's Disease, essential
      tremor, and dystonia. Recent studies have demonstrated potential for treating
      depression and obsessive-compulsive disorder.

PMID- 18807367
TI  - Clinical management of frequently encountered brain tumors.
AB  - This overview of commonly encountered brain tumors will concentrate on the three
      most common neoplasms that occur in adult medicine, e.g., gliomas, metastatic
      lesions, and meningiomas.

PMID- 18807368
TI  - The general approach and management of the sexual assault patient.
AB  - Sexual assault (SA) is unfortunately common and patients most often present to
      the emergency department, if at all. The health care provider should evaluate and
      manage the SA patient in a stepwise and detail-oriented fashion. This includes
      medical and forensic evaluation and treatment while providing for the emotional
      and legal needs of the patient. The health care provider should also understand
      the importance of medical and forensic documentation and evidence collection
      unique to the SA patient.

PMID- 18807369
TI  - Managing heart failure better: the value of implantable device data.
AB  - The heart failure disease state is challenging, time consuming and expensive to
      manage. Physicians are responsible for initiating, titrating and optimizing drug
      and device therapy to reduce morbidity and mortality. Failure to manage these
      aspects of care often results in worsening of symptoms and recurrent
      hospitalizations. This paper reviews the data implantable devices provide and how
      this data can assist in optimally managing the patient with heart failure.

PMID- 18807370
TI  - Reports mixed on Blues deal.

PMID- 18807371
TI  - Proving their worth. Post-acute providers need not wait for CMS demo.

PMID- 18807372
TI  - 2008 up & comers. 12 rising stars in healthcare demonstrate leadership acumen at
      an early age.

PMID- 18807373
TI  - Never-ending questions. Kickoff date draws near for 'never events' policy.

PMID- 18807374
TI  - Acute lung injury and acute respiratory distress syndrome in malaria.
AB  - Malaria is an important treatable cause of acute lung injury (ALI) and acute
      respiratory distress syndrome (ARDS) in the tropics and in the returning
      traveller in the non-endemic areas. ARDS is an important complication in severe,
      complicated falciparum malaria and has been described in P. vivax and P. ovale
      malaria also. Malarial ALI/ARDS is more common in adults than in children.
      Pregnant women and non-immune individuals are more prone to develop this
      condition. Increased alveolar capillary permeability resulting in intravascular
      fluid loss into the lungs appears to be the key pathophysiologic mechanism. In
      malaria, ARDS can develop either at initial presentation or after initiation of
      treatment when the parasitaemia is falling and the patient is improving. Patients
      present with acute onset dysnoea that can rapidly progress to respiratory
      failure. The diagnosis of malaria is confirmed by slide microscopy supported by
      the use of rapid antigen tests. Patients with malarial ARDS should be managed in
      an intensive care unit. Careful attention must be paid to haemodynamic
      stabilisation and optimising fluid balance. Currently, specific treatment choices
      for malaria include parenteral artemisinins or intravenous quinine along with
      doxycycline. Respiratory failure requires endotracheal intubation and assisted
      mechanical ventilation. Co-existent bacterial sepsis is frequently present in
      patients with malarial ARDS eventhough an obvious focus may not be evident.
      Appropriate broad spectrum antibiotic therapy must be started when there is a
      clinical suspicion after procuring the microbiological specimens. ARDS in malaria
      is a disease with a high mortality. Early diagnosis, institution of specific
      antimalarial treatment and assisted ventilation can be life-saving.

PMID- 18807375
TI  - Brief history of the clinical diagnosis of malaria: from Hippocrates to Osler.
AB  - Since antiquity, malaria had a major impact on world history but this brief
      historical overview focuses on clinical features of malaria from Hippocrates to
      Osler. In antiquity, physicians tried to differentiate malaria from other acute
      fevers. The classic descriptions of malaria by Hippocrates in ancient Greece and
      Celsus in ancient Rome are excerpted here from the original Greek and Latin.
      Their clear clinical descriptions prove malaria was recognized in antiquity. In
      the modern era, it remains difficult to clinically differentiate malaria from
      typhoid fever. Since physicians used the term 'typhomalaria' to describe acute
      undifferentiated fevers a testimony to their lack of clinical acumen. Osler, the
      great clinician, by careful observation in clinical features and fever patterns
      was able to clearly differentiate malaria from typhoid fever as did the ancients.

PMID- 18807376
TI  - Vulnerability of the mosquito larvae to the guppies (Poecilia reticulata) in the
      presence of alternative preys.
AB  - BACKGROUND & OBJECTIVES: The predatory potential of the larvivorous fishes can be
      affected by the presence of alternative preys. In the present study the predation
      pattern of the sewage dwelling Poecilia reticulata (Peters 1872) on the larvae of
      Culex quinquefasciatus Say 1823 (Diptera: Culicidae) was evaluated in the
      presence of alternative preys. METHODS: The predation of Cx. quinquefasciatus
      larvae by different size groups of R. reticulata fishes was evaluated. In
      addition to this, the niche breadth (N) and diet breadth (B) were measured
      following Manly's selectivity index (Si) as an indicator of variation of such
      predation pattern in the presence of alternative prey types, like chironomid
      larvae and tubificid worms. RESULTS: The consumption of IV instar Cx.
      quinquefasciatus larvae by individual P. reticulata ranged between 65 and 84 in a
      3 h feeding period and varied with the size of fish (F2,33 = 34.91; p < 0.001).
      The selectivity coefficient revealed a significantly low preference for the Cx.
      quinquefasciatus larvae (0.16, CL: 0.05-0.27; p < 0.05) compared to the
      chironomid larvae and tubificid worms, when all the three prey types were
      present. The niche breadth (N) and diet breadth (B) ranged from 0.77 to 0.92 and
      0.69 to 0.93, respectively. The total consumption of all the prey types varied
      with the predator density, but the selectivity index for the mosquito larvae was
      significantly low in all the instances. INTERPRETATION & CONCLUSION: P.
      reticulata can consume a good number of mosquito larvae, with the consumption
      rate varying with the body size. P. reticulata fishes exhibit low preference for
      mosquito larvae as prey in the presence of alternative controphic preys like
      chironomid larvae and tubificid worms. Though establishment and sustenance of P.
      reticulata in new habitats will be favoured by the presence of alternative preys,
      but vulnerability of mosquito larvae may be reduced with availability of multiple
      preys in natural conditions.

PMID- 18807377
TI  - RT-PCR assay for the detection of infective (L3) larvae of lymphatic filarial
      parasite, Wuchereria bancrofti, in vector mosquito Culex quinquefasciatus.
AB  - BACKGROUND & OBJECTIVES: Periodic monitoring of vector population for infection
      and infectivity rates is central to the evaluation of the filariasis elimination
      strategies in endemic areas to monitor the success of MDA and also to establish
      endpoints for intervention. The main objective of this study was to develop a RT
      PCR assay, based on L3 stage-specific primers to detect the presence of infective
      stage larvae of filarial parasite, Wuchereria bancrofti in the vector Culex
      quinquefasciatus. MATERIAL & METHODS: Subtracted probe development technique was
      employed for the identification of infective stage (L3) specific genes. The
      subtracted cDNA was labeled by non-radioisotopic method and used for screening
      cDNA library of L3 stage larvae of W. bancrofti constructed in UniZap XR.
      Recombinants were probed and identified from the library. The inserts of the
      recombinant clones were purified and sequenced. Primers were designed based on
      the sequence information of three recombinant clones for detecting L3 larvae of
      W. bancrofti in the vector by RT-PCR assay. Preliminary laboratory evaluation was
      carried out to assess the sensitivity and specificity of WbL31 RT-PCR assay.
      RESULTS: cDNA library of L3 stage of W. bancrofti constructed in UniZap XR
      vector, constituted 5 x 10(5) phages with 80-90% recombinant phages and the size
      of inserts varied from 0.1 to 1.0 kb. When subtracted cDNA was random prime
      labeled and used for screening cDNA library of L3 stage of W. bancrofti
      constructed in UniZap XR, 18 clones were identified from the library. Three genes
      were found up-regulated in the L3 stage, out of which WbL31 (cuticular collagen)
      was found to be useful in detecting L3 larvae of W. bancrofti in the vector by RT
      PCR assay with high specificity and sensitivity (98-100%). CONCLUSION: Present
      paper marks first report on the development of an infective stage-specific RT-PCR
      assay (WbL31 RT-PCR assay) to detect L3 stage W. bancrofti in the vector. This
      assay will have potential application in assessing the transmission of infection
      and hence in decision-making related to elimination programme.

PMID- 18807378
TI  - Malaria prevention practices among mothers delivering in an urban hospital in
      southwest Nigeria.
AB  - BACKGROUND & OBJECTIVES: The pregnant woman is more prone to malaria than her non
      pregnant counterpart with grave consequences for both mother and baby. This study
      aims at determining the malaria prevention practices among pregnant women in an
      area hyper-endemic for malaria. METHODS: For the study 983 parturient mothers
      were enrolled in Ibadan, southwest Nigeria. Information was collected on
      sociodemographic characteristics, use of malaria chemoprophylaxis, use of anti
      vector measures, and malaria parasitaemia. RESULTS: Most mothers [956/972
      (98.4%)] reported the use of anti-vector measures for malaria prevention. These
      include, window screens (78.9%), insecticides spray (69.9%), mosquito coils
      (25.3%), untreated bednets (2.5%), and insecticide-treated nets (1.1%). Most
      mothers used anti-vector measures either singly or in combination. About 86%
      (840/972) of the mothers used drugs for chemoprophylaxis. Thirteen (1.3%) mothers
      used chemoprophylaxis alone (CP), 135 (13.9%) used anti-vector measures alone
      (AV) while 820 (84.4%) used chemoprophylaxis plus anti-vector (CPAV). Weekly dose
      of pyrimethamine [214 (25%)] and intermittent preventive treatment with
      sulphadoxine-pyrimethamine [598 (71.2%)] were the widely used chemoprophylactic
      drugs. The prevalence of patent parasitaemia at delivery was 7.7% (1/13), 12.1%
      (99/820) and 16.3% (22/135) among CP, CPAV and AV groups respectively. Geometric
      mean parasite densities among the respective groups were 7840/microl, 1228/microl
      and 8936/microl. CONCLUSION: Window screens and insecticide sprays were widely
      used for malaria prevention while the use of ITN was very low among enrolled
      mothers. There is a need to pay concerted efforts to improve ITN usage rate in
      Nigeria.

PMID- 18807379
TI  - Transmission dynamics of Simulium damnosum in rural communities of Akwa Ibom
      State, Nigeria.
AB  - BACKGROUND & OBJECTIVES: Onchocerciasis is endemic in some parts of Akwa Ibom
      State, Nigeria. This study describes the entomological parameters of transmission
      in three rural communities of Akwa Ibom State, prior to ivermectin intervention
      in 2004. METHODS: Blackflies were caught using human bait and 90% of the flies
      were dissected for parity. All parous flies were further dissected for the
      presence of filaria larvae. Monthly and annual biting rate, and transmission
      potential were calculated using standard methods. RESULTS: A total of 4296 adult
      Simulium damnosum were caught on human bait, 4119 were dissected of which 208
      (5.1%) were infected with Onchocerca volvulus larvae. Transmission parameters
      varied significantly (p < 0.05) in the three villages. Annual biting rates,
      ranged from 9490 to 11,218 bites per person per year. The annual transmission
      potential ranged from 131 to 189 infective larvae per person per year, monthly
      biting rate and monthly transmission potential varied significantly (p < 0.05) in
      the three villages. Transmission was highly seasonal occurring during the peak of
      rainy season from August to October. There was no transmission during the dry
      periods--November to March, and the early rainy periods--April to May. The
      diurnal biting activity of the fly exhibited a bimodal pattern with a morning
      peak (0900-1000 hrs) and a more marked evening peak (1600-1700 hrs).
      INTERPRETATION & CONCLUSION: The results indicate that there is a temporal and
      spatial variation in the transmission dynamics of S. damnosum in the study area.

PMID- 18807380
TI  - Studies on prevalence of anopheline species and community perception of malaria
      in Jaffna district, Sri Lanka.
AB  - BACKGROUND & OBJECTIVES: Over two decades of civil unrest and the conflict
      situation have had detrimental effects on vector control activities and
      management of malaria in Jaffna district which is an endemic region for malaria
      in Sri Lanka. With the background that only a few small-scale studies on malaria
      and its vectors have been reported from this district, a study was designed to
      explore the current status of malaria in the Jaffna district in relation to
      vector and community aspects. METHODS: Adults and larvae of anopheline mosquitoes
      were collected monthly from selected endemic localities. Species prevalence of
      the collected mosquitoes was studied while the collected adults of Anopheles
      subpictus, a potential vector in the district, was screened for sibling species
      composition based on morphological characteristics and exposed to common
      insecticides using WHO bioassay kits. Knowledge, attitude and practices (KAP) of
      the community were tested using a pre-tested structured questionnaire in high
      risk and low-risk localities in the district. RESULTS: The anopheline mosquito
      species distribution in the district was--An. culicifacies (0.5%), An. subpictus
      (46%), An. varuna (4%), An. nigerrimus (44%) and An. pallidus (5.5%). Among the
      collected larvae the percent prevalence of An. culicifacies was 13% and other
      species follows as: An. subpictus (71%), An. varuna (4%), An. nigerrimus (10%)
      and An. pallidus (2%). Sibling species B, C and D of An. subpictus were present
      in the district with the predominance of B in both coastal and inland areas,
      while all members showed both indoor and outdoor resting characteristics, they
      were highly resistant to DDT (4%) and highly susceptible to malathion (5%). KAP
      study in the district showed a reasonable level of knowledge, positive attitude
      and practices towards malaria. CONCLUSION: An. subpictus, the reported major
      vector of Jaffna and a well-established secondary vector of malaria in the
      country, continues to be the predominant anopheline species. The distribution of
      sibling species of An. subpictus complex in the Jaffna district, revealed for the
      first time, has implications for future studies on its bionomics and malaria
      transmission pattern in this area and the planning of control strategies for this
      region. The community perception of disease, which revealed a satisfactory
      knowledge indicates the potential for better community participation in future
      malaria control activities in this region. As potential vectors are still
      present, health authorities need to be vigilant to prevent any future epidemics
      of malaria.

PMID- 18807381
TI  - Mosquito larvicidal constituents from Lantana viburnoides sp viburnoides var kisi
      (A. rich) Verdc (Verbenaceae).
AB  - BACKGROUND & OBJECTIVES: Lantana viburnoides sp viburnoides var kisi is used in
      Tanzania ethnobotanically to repel mosquitoes as well as in traditional medicine
      for stomach ache relief. Bioassay-guided fractionation and subtraction bioassays
      of the dichloromethane extract of the root barks were carried out in order to
      identify the bioactive components for controlling Anopheles gambiae s.s. mosquito
      larvae. METHODS: Twenty late III or early IV instar larvae of An. gambiae s.s.
      were exposed to various concentrations of the plant extracts, fractions, blends
      and pure compounds, and were assayed in the laboratory by using the protocol of
      WHO 1996. Mean mortalities were compared using Dunnett's test (p < 0.05) and
      lethal concentration calculated by Lackfit Inversel of the SAS programme.
      RESULTS: The crude extract (LC50 = 7.70 ppm in 72 h) and fractions exhibited
      different level of mosquito larvicidal activity with subtraction of some
      fractions resulting in activity enhancement. The active fractions contained
      furanonaphthaquinones regio-isomers (LC50 = 5.48-5.70 ppm in 72 h) and the
      lantadene triterpenoid camaric acid (LC50 = 6.19 ppm in 72 h) as active
      principles while the lupane triterpenoid betulinic acid (LC50 < 10 ppm in 72 h)
      was obtained from the least active fraction. INTERPRETATION & CONCLUSION: Crude
      extracts and some fractions had higher or comparable larvicidal activity to the
      pure compounds. These results demonstrate that L. viburnoides sp viburnoides var
      kisi extracts may serve as larvicides for managing various mosquito habitats even
      in their semi-purified form. The isolated compounds can be used as distinct
      markers in the active extracts or plant materials belonging to the genus Lantana.

PMID- 18807382
TI  - Historical analysis of the economic cost of dengue in Australia.

PMID- 18807383
TI  - Field evaluation of malathion fogging against Japanese encephalitis vector, Culex
      tritaeniorhynchus.

PMID- 18807384
TI  - Reactivation of Herpes zoster in an adult with Plasmodium infection.

PMID- 18807385
TI  - [Colloid-physical characterization of supramolecular drug delivery systems].
AB  - Cyclodextrins are well-known biocompatible oligosaccharides capable of forming
      inclusion complexes with suitable guest molecules. They can be expediently used
      as solubilizers for hydrophobic pharmacon molecules in aqueous solutions. In this
      study, the effect of colloidal and non-colloidal additives on the solubility of
      statins is described. Two statin-derivatives (lovastatin and simvastatin), beta
      cyclodextrin (-CD) and randomly methylated beta-cyclodextrin (RAMEB) were used as
      complexing agents. Those pharmacons are widely used in the management of
      cardiovascular diseases involving high or elevated blood cholesterol levels.
      Complexation of the highly lipophilic statin molecules with beta-CD and RAMEB was
      studied in the presence and the absence of dissolved polyvinyl-pyrrolidone (PVP).
      For the characterization of the stability of statin-CD complexes, association
      constant of binary associates have been calculated. It was found that inclusion
      complexation can beneficially enhance the solubility of both statin-derivatives.
      In binary statin-CD solutions predominantly associates of 1:1 molar ratio form,
      which show significant surface activity. In polymer-containing ternary systems,
      the solubility of the pharmacons can further be increased. This phenomenon can
      presumably be explained with the formation of statin-CD-polymer ternary
      associates of supramolecular structure. In such supramolecular assemblies the
      amphiphilic statin-CD complexes are likely bound to the macromolecules' chains.
      The wetting properties of solid, dried and powdered complexes were studied by
      immersion enthalpy measurements. Both in binary and ternary systems a significant
      increase in the immersion enthalpy values could be detected, which indicates that
      the complexes exhibit fairly hydrophilic character.

PMID- 18807386
TI  - [Methods to increase the encapsulation efficiency for liposomal drugs].
AB  - Liposomes as drug delivery systems--in comparison to the traditional dosage forms
      -offer the advantage of the targeted drug delivery and as a consequence,
      reduction of the side effects. In case of fluoroquinolone antibiotics, such as
      lomefloxacin, the liposomal encapsulation of the active ingredient can result in
      an enhancement of its therapeutic efficacy against intracellular bacteria. The
      aim to improve the liposomal encapsulation efficiency of drugs--which is one of
      the main factors influencing the therapeutic effect of vesicular dosage forms--is
      one of the important challenges in the field of pharmaceutical technology. In our
      experiments we prepared lomefloxacin containing multilamellar vesicles from
      various lipids using different hydrating solutions. We intended to study the
      effect of lipid composition, cholesterol content and surface charge of liposomes
      on the encapsulation efficiency of lomefloxacin. Our results can contribute to
      the rational design of fluoroquinolone containing liposomal drugs.

PMID- 18807387
TI  - [Novel method for the synthesis of carboxamides from low reactivity esters:
      synthesis of 2-acylamino-1-benzothiophene-3-carboxamides].
AB  - We planned and prepared a kinase inhibitor focused compound library around the 1
      benzotiophene core structure, but the 2-acylamino-1-benzotiophene-3-carboxylic
      acid ethyl ester derivatives could not be converted to amides by the traditional
      methods like treatment with aqueous or alcoholic ammonia solution or ammonia gas.
      Under mild reaction conditions we have recovered the starting materials, higher
      temperature and pressure resulted the formation of pure ring-closed products. We
      have discovered a new method where the application of lithium amide in
      tetrahydrofurane resulted the desired compounds in acceptable yields (67-84%).
      The products were characterized thoroughly by spectral data, elementary analyses
      and melting points.

PMID- 18807388
TI  - [Cost study of NSAID use in rheumatoid arthritis based on recent therapeutic
      protocols].
AB  - In today's health care beside the medical perspective, economic aspects should
      also be taken into consideration. Because of the significant opportunity-cost,
      only the most cost-effective techniques should be subsidized, which result the
      highest net-benefit for the society. This paper focuses on the economic aspects
      of the chronic NSAID use in rheumatoid arthritis. Based on recent therapeutic
      protocols a cost study (partial economic evaluation) was carried out. Our results
      indicate that for patients with an average GI-risk retard diclofenac could be a
      possible good choice. For patients with moderate to severe GI risk, retard
      diclofenac + pantoprazole combination therapy should be prescribed. COX-2
      inhibitors are advised only for a limited group of patients with specific
      conditions; because of their higher price and side effect profile (severe CV
      adverse effect and uncertain GI benefits). We would also highlight the importance
      of individual therapy. In complex our purpose was to evaluate current therapeutic
      guidelines from a pharmacoeconomic perspective.

PMID- 18807389
TI  - [Site-specific drug delivery systems. III. Nasal drug delivery].
AB  - The nasal cavity has a large surface and a rich blood supplied mucosa. Drugs
      absorbed by blood vessels pass directly into the systemic circulation, thereby
      avoiding first-pass metabolism. Numbers of factors limit the intranasal
      absorption of drugs, especially peptide and protein drugs. These factors are the
      epithelial and mucus barrier, the rapid mucociliar clearance and the enzymatic
      activity. Increasing the residence time of the drug formulation in the nasal
      cavity and a period of contact with nasal mucosa, may improve drug absorption.
      Approaches to increase the residence time of drug formulations in the nasal
      cavity usually involve the use of microspheres, liposomes and bioadhesive gels.

PMID- 18807390
TI  - Arterialized venous free flaps--a reconstructive alternative for large dorsal
      digital defects.
AB  - Venous free flaps should be considered as potential reconstructive options for
      large dorsal digital defects with exposed bone, joint and/or extensor tendons, if
      local flaps are inadequate or unusable. We describe our experience of thirteen
      venous free flaps in twelve patients with large dorsal digital defects. Our
      survival rate for these flaps is comparable to the published data. The forearm
      donor site was closed primarily in all cases with minimal morbidity. The flaps
      should be monitored with Doppler devices as clinical evaluation is misleading
      secondary to the venous congestion inherent in these flaps. This reconstructive
      option has become a well-established procedure in our hands and is the alternate
      reconstructive method of choice for large dorsal digital defects where local
      flaps are not usable or inadequate due to complex hand injuries or multiple
      finger defects.

PMID- 18807391
TI  - Reconstruction of large upper lip defects by free tissue transfer.
AB  - Reconstruction of a large upper lip defect is a demanding procedure and can be
      performed by a variety of local flaps or by microvascular free tissue transfer.
      We present our experience in reconstructing near total or total upper lip defects
      by free tissue transfer. In 11-year period seven patients underwent microvascular
      reconstruction of upper lip, six with non-innervated radial forearm flap and one
      with non-innervated anterolateral thigh flap. In all patients good functional and
      acceptable aesthetic results, with oral competence at rest and during eating and
      speaking, were achieved. Deglutition and articulation were not affected in any
      patient. Sensory evaluation of reconstructed upper lips was performed in four
      patients and in three a reasonable recovery of sensation was recorded. In our
      opinion subtotal or total upper lip reconstructions with folded thin fascio
      cutaneous free flaps produce very good functional and aesthetically acceptable
      results and avoid additional scars on lower lip and cheek. Further, because the
      size of the mouth is not altered, microstomia is avoided, which is especially
      important for patients using dentures. The remaining disadvantage of this method
      is non-competence of orbicularis oris muscle sphincter.

PMID- 18807392
TI  - The value of clinical diagnosis of digital glomus tumors.
AB  - Glomus tumors are benign neoplasms that differentiate from the glomus apparatus.
      This neoplasm is clinically characterized by a typical symptomatological triad:
      paroxysmal pain, pinpoint pain and hypersensitivity to cold. The diagnosis is
      usually clinical, but can be confirmed by instrumental tests such as X-ray, MRI,
      selective arteriography and most commonly by ultrasound, with or without Doppler.
      Surgical resection of the glomus tumor is the definitive treatment with
      resolution of all symptoms. From 1997 to 2007, 21 surgically-treated cases were
      reviewed and here we report the clinical assessment that was used. The nine most
      recent cases of glomus tumor underwent surgery after clinical assessment alone.
      In our opinion clinical examination is the most effective method to diagnose this
      type of tumor and in selected cases it may be sufficient to undergo surgical
      therapy.

PMID- 18807393
TI  - Giant cell reparative granuloma in the mandible--case report and review of the
      literature.
AB  - OBJECTIVE: Central giant cell granuloma (GCG) is defined as an intraosseous
      lesion consisting of cellular fibrous tissue containing multiple foci of
      hemorrhage, aggregations of multinucleated giant cells. Peripheral GCG is a
      reactive exophytic lesion occurring on the gingiva and alveolar ridge originating
      from the periosteum or periodontal membrane, usually as a result of local
      irritating factors. STUDY DESIGN: The case report evaluated long-term therapy of
      giant cell granuloma. A 9-year-old boy generally healthy was admitted to our
      clinic with a swelling in the frontal area of mandible. Giant cell granuloma was
      detected. Surgical curettage was applied. After 3 years of the operation, the
      recurrence was seen during the physical examination. The new GCG was removed. The
      prosthetic rehabilitation including implants insertion (18-year-old adult
      patient) finished treatment. RESULTS: Three-year recall confirmed the stability
      of treatment. CONCLUSION: Esthetical and functional therapy is of great
      importance in the patient's rehabilitation.

PMID- 18807394
TI  - Ipsilateral fibular transfer: a valuable option for treatment of large tibial
      defects in children.
AB  - Large tibial defects pose a great therapeutical challenge. Defects longer than 5
      cm should be treated using various techniques with almost similar final results.
      Besides the method of bone lengthening and free fibular flap, there is also the
      possibility of reconstruction with ipsilateral fibular transfer. This method,
      mainly for children and adolescents, is now still an alternative with only few
      complications which should not be abandoned. We present the case of a 6-year-old
      boy with floating knee and tibial fracture with excessive bone loss which was
      solved by ipsilateral fibular transfer as a 2-stage procedure.

PMID- 18807395
TI  - Majority of emergency patients don't understand discharge instructions.
AB  - ED managers, responding to a study that showed more than 75% of patients do not
      understand their discharge instructions, list several options for improving
      communications. They include: Have several providers discuss with the patient
      their condition, treatment, and follow-up instructions. Make sure discharge
      instructions are written at a fourth-grade reading level or lower. Initiate a
      project in your department to shorten your discharge instruction forms.

PMID- 18807396
TI  - ED's nonemergent patients must pay first or be referred.
AB  - Patients presenting to your ED with complaints that should be seen by a primary
      care physician can exacerbate overcrowding and tie up staff unnecessarily. The ED
      at Metro Health Medical Center in Cleveland has addressed this problem with a two
      pronged approach: Nonemergent patients who are uninsured but wish to be treated
      in the ED must pay $75 before treatment can begin. Patients also are offered the
      option of being referred to one of the system's neighborhood clinics. Referred
      patients are guaranteed they will be seen within 72 hours.

PMID- 18807397
TI  - Flood fails to 'wash out' ED's ability to communicate.
AB  - When disaster strikes, communication often can be one of the first victims.
      However, during the recent floods in Iowa the communications in the ED at Mercy
      Medical Center in Cedar Rapids, IA, continued working flawlessly due to system
      redundancies and advanced planning. The strategies included: a wireless
      documentation system that was not dependent on being in a specific room or
      location; phones using a Voice over Internet Protocol, which enabled them to be
      plugged into any jack in the building; a statewide radio system that enabled the
      staff to speak to other hospitals about potential patient transfers.

PMID- 18807398
TI  - Documentation tool can boost bottom line.
AB  - ED managers and consultants who have used documentation templates to augment
      their coding and billing activities say such systems enable EDs to collect all
      the revenue they are entitled to. Such tools, they say, offer several advantages:
      The more robust products understand what third-parties require to obtain optimal
      reimbursement. The products can prompt the ED manager to perform the tests that
      will yield the most revenue for a specific condition. You can further enhance the
      value of those products by hiring a staff member to review your charts for
      thoroughness and timeliness.

PMID- 18807399
TI  - Many psychiatric patients wait 24 hours to be seen.
AB  - The current state of care for psychiatric ED patients leaves much to be desired,
      as illustrated by the recent waiting room death of a patient in a Brooklyn
      psychiatric ED and new survey findings from the American College of Emergency
      Physicians. Experts recommend several options for improving care for those
      patients. The creation of a psychiatric ED, which is specifically designed to
      manage such patients; a separate, locked area within the ED devoted to
      intoxicated and incarcerated patients and patients staffing that includes nurse
      specialists, social workers, or nurse practitioners and physician assistants with
      specialized training in mental health.

PMID- 18807400
TI  - Inclusion, itinerant teachers, and the pull-out model.

PMID- 18807401
TI  - Deaf education and bridging social capital: a theoretical approach.
AB  - The authors use elements of social capital theory to explore the rapidly changing
      landscape of deaf education in America. They suggest that the formation of
      relationships, and networks of relationships, between deaf students and adults
      has a value that often goes undetected or underappreciated in deaf education. The
      authors point out that social capital theory, as applied to deaf education,
      generates a number of potentially productive areas for improving outcomes among
      deaf students, and for future research in the field. The article includes
      discussion of a number of positive steps to promote bridging social capital among
      deaf students.

PMID- 18807402
TI  - Coenrollment for students who are deaf or hard of hearing: friendship patterns
      and social interactions.
AB  - Third- and fourth-grade students in two separate classrooms--one a classroom with
      only hearing students and the other a coenrolled classroom with hearing, hard of
      hearing, and deaf students--were assessed to determine friendship patterns,
      attitudes, beliefs, and perceptions about sign language and deafness. Sociograms,
      interviews, and videotape analysis of the students' responses were done. Results
      suggest that hearing students in the coenrolled classroom had better sign
      language skills, a more positive attitude toward deafness, and an improved
      awareness of certain aspects of hearing loss (such as speech and amplification).
      Deaf and hard of hearing students' social acceptance was similar to that of their
      hearing peers.

PMID- 18807403
TI  - Engagement during reading instruction for students who are deaf or hard of
      hearing in public schools.
AB  - An observational study of reading instruction was conducted in general education,
      resource, and self-contained classrooms, grades 1-4, in public schools.
      Participants included students who were deaf or hard of hearing and their reading
      teachers. Results indicated that time engaged in reading and/or academically
      responding varied significantly by grade level enrolled, reading curriculum grade
      level, and instructional setting, but not level of hearing loss or presence or
      absence of concomitant conditions. Students working with reading curriculum one
      grade level below spent significantly less time in reading instruction and
      reading than students working on grade level or two levels below. Students in
      general education settings spent significantly more time in reading instruction
      and reading silently than students in self-contained settings. The probability
      that students would engage in reading was significantly increased by several
      teacher and ecological conditions more likely to be observed in general education
      settings.

PMID- 18807404
TI  - Providing online course opportunities for learners who are deaf, hard of hearing,
      or hearing.
AB  - For more than 20 years, two courses, History, Education, and Guidance of the
      Deaf/Hard of Hearing and Introduction to Instructional Methods for the Deaf/Hard
      of Hearing, have been taught at Bloomsburg University of Pennsylvania using a
      traditional lecture format. A state grant provided funding to explore the use of
      technology to teach online courses to college-age learners who are deaf, hard of
      hearing, or hearing. Saba Centra software was used as the online tool for the
      synchronous presentation of course content, which included PowerPoint lecture
      material, text chat opportunities, sign language-interpreted video, and other
      forms of class participation (e.g., signaling for questions raised, responding in
      a "yes/no" format). The present article covers recent successes and challenges in
      offering online courses in a "virtual classroom" format to deaf and hard of
      hearing learners, as well as hearing learners, from a qualitative research
      perspective.

PMID- 18807405
TI  - Professionalism and coordination: allies or enemies?
AB  - Professionalism arose concurrently with coordination policies among service
      providers and between parents and service providers in deaf education practices.
      The author examines the effects of professionalism on coordination among service
      providers from different disciplines (deaf education, speech-language pathology,
      elementary education, secondary education, audiology, otolaryngology, and
      pediatrics), as well as coordination between parents and these service providers
      in multidisciplinary, interdisciplinary, and transdisciplinary teams in the light
      of her own experience as a teacher of children who are deaf and hard of hearing
      in Cyprus. The author concludes that professionalism and coordination can
      coexist, and that the key issue in this relationship is the personal attitudes of
      those involved.

PMID- 18807406
TI  - Towards integrated practices in early detection of and intervention for deaf and
      hard of hearing children.
AB  - It is well documented that undetected hearing loss can have a profound effect on
      a child's holistic development, including communicative, language and cognitive
      development. It is crucial therefore that deaf and hard of hearing infants are
      detected as early as possible so that appropriate intervention services and
      support can be initiated. To assist parents in enabling their child's optimal
      growth and development, HI HOPES-the first South African home-based early
      intervention project-was launched in August 2006, offering families weekly home
      based support that is both child-centred and family-directed. A critical overview
      of the pilot implementation of HI HOPES is presented, from inception to
      implementation, focusing on its innovative services and practices, and issues
      that influence the intervention process including a reflection on the challenges
      and areas for development.

PMID- 18807407
TI  - College and university requirements for teachers of the deaf at the undergraduate
      level: a twenty-year comparison.
AB  - College and university requirements for undergraduate deaf education teacher
      preparation programs from 1986 and 2006 were compared. Thirty percent fewer
      undergraduate programs were in existence in 2006 than in 1986. Compared to
      programs in the 1986-1987 academic year, programs in 2006-2007 placed less
      emphasis on course work related to speech and hearing and more emphasis on the
      development of sign language skills. These findings are discussed in relation to
      the increasing probability that future employment for program graduates will be
      in itinerant and resource placements within public schools with children whose
      hearing losses are less severe than those of children in the past.

PMID- 18807408
TI  - National study of master teachers in deaf education: implications for teacher
      education.
AB  - After an extensive review of relevant literature, the investigators developed a
      questionnaire on teacher characteristics and behaviors in relation to master
      teachers and distributed it electronically to deaf education professionals. The
      questionnaire recipients represented administrators, experienced teachers (e.g.,
      those with 3 or more years' experience), and college and university faculty
      responsible for preparing teachers of the deaf. Follow-up interactive interviews
      were conducted with representatives of each constituency. Considerable
      similarities were noted in the priorities assigned across the three different
      constituencies, including a value placed on strong communication skills, having a
      passion about teaching, being collaborative, remaining current in the field,
      helping students become independent learners, and employing cognitive strategies.
      Analyses of responses by constituency are provided, along with recommendations
      for action, particularly for teacher education programs that are intent on
      graduating more teachers with master teacher potential.

PMID- 18807409
TI  - The DNP* storm.

PMID- 18807410
TI  - Transition to an individual-room NICU design: process and outcome measures.
AB  - Redesign of a neonatal intensive care unit is a major budget undertaking,
      demanding accountability for its equipment and feasibility of design. It must be
      philosophically based and driven by research supporting best practice. The NJCU
      at the Magee-Womens Hospital of the University of Pittsburgh Medical Center, a
      Level III, 74-bed unit, has made the change from a ward design to an individual
      room design suitable for family-centered, developmentally supportive care. This
      article presents the design process as it occurred. Unique to this process are
      the involvement of NJCU-graduate families and the use of transition teams.
      Guidelines and recommendations are offered to others interested in designing and
      practicing in an individual-room NJCU. Outcome data demonstrate staff adjustment
      to the new design and practice model. A comparison of this NICU design is made
      with the Recommended Standards for Newborn ICU Design.

PMID- 18807411
TI  - A case presentation of early intervention with dolichocephaly in the NICU:
      collaboration between the primary nursing team and the developmental care
      specialist.
AB  - Dolichocephaly, narrow width and long anterior-posterior cranial distance, is
      more commonly seen in preterm than in term infants. It seems to persist after
      NJCU discharge and may be a marker for adverse neurodevelopment. This article
      reports a case of cranial molding in one extremely low birth weight infant. He
      was placed on a viscoelastic mattress and a twice weekly developmental care
      program. Cranial molding was measured using the cranial index (CI), a ratio of
      width to length. Initially, the patient presented with dolichocephaly (CI=72
      percent). y week 2, CI measurements approached normal limits (CI=75 percent).
      When placed on continuous positive airway pressure, the infant presented with
      substantial dolichocephaly (CI=66.7 percent). Following position changes to
      midline, CI measurements continued to improve and remained within normal limits
      until discharge. This dual-element program was feasible, acceptable to parents
      and staff and may be effective for identifying and managing dolichocephaly.

PMID- 18807412
TI  - Music as a nursing intervention for preterm infants in the NICU.
AB  - Although there is general agreement that noise in the neonatal intensive care
      unit should be reduced, there is controversy about the use of music as a
      developmental care strategy with prererm infants. Much literature supports using
      music with preterm infants, indicating that it enhances physiologic and
      neurobehavioral functioning, but some experts worry that music is
      overstimulating. This article presents evidence supporting the use of music with
      preterm infants as well as criticism of same. Recommendations for music
      interventions with preterm infants are discussed, although fUrther research is
      needed before specific guidelines can he established.

PMID- 18807413
TI  - Cerebral monitoring of the term infant.
AB  - Continuously monitoring brain ftinction at the bedside in the NICU for term
      infants at risk of brain injury has become part of routine clinical practice in
      many countries. These monitors offer invaluable information about the sick
      infant's neurologic status by providing real-time measurements of the brain's
      electrical activity and identifring or confirming seizure activity. With the
      increasing availability of bedside electroencephalogram technology, it is
      essential for neonatal intensive care nursing staff to understand the rationale
      for its use, as well as the fundamentals of application and interpretation of
      this new technology.

PMID- 18807414
TI  - Brain type natriuretic peptide.

PMID- 18807415
TI  - Vancomycin prophylaxis for late-onset sepsis in very low and extremely low birth
      weight neonates.

PMID- 18807416
TI  - Keeping a watchful eye on retinopathy of prematurity.

PMID- 18807417
TI  - Note on using positional aid.

PMID- 18807418
TI  - Sex differences in subjective distress to unfaithfulness: testing competing
      evolutionary and violation of infidelity expectations hypotheses.
AB  - According to an evolutionary psychology perspective, men's and women's processing
      of threats to their sex-linked mate selection strategies cause sex differences in
      infidelity distress. An alternative account assumes that the distress results
      from men's and women's processing of expectation violations regarding the content
      of an unfaithful partner's actions with a rival. Logistic regressions supported
      the conclusion that the participant's sex-but not the processing of expectation
      violations-was the best predictor of the most distressing infidelity presented in
      forced-choice, mutually exclusive, and combined formats. Our results also
      indicated that the sex differences in infidelity distress were neither limited to
      using data from a forced-choice response format nor caused by the distinct
      inferences that men and women draw about the relation between love and sex.

PMID- 18807419
TI  - Asymmetrical effects of reward and punishment on attributions of morality.
AB  - The authors found that 3 experiments revealed that compliance with a pro-social
      request for an anticipated reward as opposed to a threatened punishment resulted
      in greater inferences of personal morality. In Experiment 1, participants
      received information about a teaching assistant (TA) who was either promised a
      reward or threatened with a punishment when asked for compliance. The
      participants perceived the TA as more moral for complying given the positive
      incentive as opposed to the negative incentive. Experiment 2 replicated this
      finding in a different culture, using different vignettes and incentives. Last,
      in Experiment 3, the results revealed that a perceived actor's real intentions
      mediated the effect of incentive valence on dispositional causation. That is,
      given a reward relative to a punishment, participants were more likely to assume
      that the agent would have helped even if no incentive had been offered.

PMID- 18807420
TI  - Intrapersonal variation in consumer susceptibility to normative influence: toward
      a better understanding of brand choice decisions.
AB  - The authors examined intrapersonal variation in consumer susceptibility to
      normative influence as a key mediator of wine brand choice. On the basis of a
      consumer sample, the authors found that individual values and social identity
      complexity affect consumer susceptibility to normative influence with downstream
      effects on (a) which brand benefits consumers desire in wine and (b) choice.
      Individuals higher on internal values and with more complex social identities
      were less susceptible to normative influence and placed less emphasis on social
      brand benefits. Separate examinations of consumption scenarios with and without
      salient reference groups showed that reference group salience interacts with
      personal values and social identity complexity in affecting consumer
      susceptibility to normative influence, which in turn affects which brand benefits
      consumers desire and consequently choice.

PMID- 18807421
TI  - Implicit orientation toward family and school among bilingual Latino college
      students.
AB  - The authors examined the associations that underlie the orientations of bilingual
      Latino college students toward family and school. Participants completed, in
      English or Spanish, 3 implicit association tests assessing their attitude toward
      family vs. school, identifications with these concepts, and self-esteem. Results
      revealed a more positive attitude toward, and stronger identification with,
      family than school. Identification with family was stronger among participants
      who completed the study in English, suggesting self-definition in terms of
      distinctions from the context. Last, the more participants valued family over
      school and identified with family rather than school, the higher was their self
      esteem. These findings shed light on the subtle, yet crucial, mechanisms by which
      cultural knowledge is incorporated in the self-concept of bilingual Latino
      college students.

PMID- 18807422
TI  - Predicting attendance at peer-assisted study sessions for statistics: role
      identity and the theory of planned behavior.
AB  - Using a prospective study of 77 1st-year psychology students' voluntary
      attendance at peer-assisted study sessions for statistics, the authors tested the
      addition of role identity to the theory of planned behavior. The authors used a
      revised set of role-identity items to capture the personal and social aspects of
      role identity within a specific behavioral context. At the commencement of the
      semester, the authors assessed the students' attitudes, subjective norm,
      perceived behavioral control, role identity, and intention. The authors examined
      the students' class attendance records 3 months later. Attitudes and perceived
      behavioral control predicted intention, with intention as the sole predictor of
      attendance. Role identity also predicted intention, reflecting the importance of
      the student role identity in influencing decision making related to supplementary
      academic activities.

PMID- 18807423
TI  - The influence of relationship status, mate seeking, and sex on intrasexual
      competition.
AB  - Researchers have little explored individuals' perceptions of same-sex
      attractiveness in terms of the influence of relationship status. By using
      intrasexual competition as a conceptual framework, the authors predicted that
      romantically involved individuals would protect their relationship by derogating
      competitors. Although previous researchers have strongly predicted this result,
      in the present study the relationship status had a negligible impact on
      competition, for which relationship commitment, sociosexual orientation, and self
      monitoring did not account. Also, among uninvolved individuals, the authors
      expected those individuals seeking mates would use competitor derogation more
      than would those individuals not seeking mates, but there was no significant
      difference. Finally, because the vehicle for this investigation was
      attractiveness, an area in which women compete, the authors proposed that women
      would derogate more fiercely than would men. However, the results did not support
      this hypothesis either. The authors discuss future directions for research.

PMID- 18807424
TI  - Building the bridge to a "more perfect" healthcare system.

PMID- 18807425
TI  - Serum lipids in patients with stroke--a cross-sectional case-control study.
AB  - BACKGROUND: Vascular disease remains the prime contributor to the pathogenesis of
      stroke, but dyslipidemia has not been clearly established as a risk factor for
      stroke the same way it has been for coronary artery disease. There is no case
      controlled study on the contribution of serum lipids to stroke in Nigerians. This
      study aimed at assessing the possibility of serum lipids as risk factor for
      stroke in Nigerian patients. METHOD: The demography, blood pressure, fasting
      plasma glucose and fasting serum lipids of 87 consecutive patients with first
      ever stroke managed at the University of Benin teaching hospital between January
      and December 2005 were analyzed and compared with those of age- and sex-matched
      controls. RESULTS: Eighty-seven stroke patients (55 males and 32 females; mean
      age 61.25 +/- 14.77 years) were compared with age- and sex-matched controls.
      Ischemic stroke constituted 64.37%, while the rest had hemorrhagic stroke. There
      were no significant differences in the serum cholesterol, HDL-C and LDL-C levels
      of stroke patients and controls (p > 0.05), but the serum triglyceride level was
      higher among the stroke patients (p < 0.001) with a significant relative risk (RR
      = 1.77; p < 0.01). CONCLUSION: In this cross-sectional case-control study, there
      is no significant difference in the serum lipids of Nigerian patients with stroke
      with the exception of serum triglyceride, which seems to confer significant
      stroke risk.

PMID- 18807426
TI  - Explaining the relationship between pain and depressive symptoms in African
      American and white women with arthritis.
AB  - Arthritis is a common chronic illness that disproportionately affects women and
      African Americans and is often associated with depression. The mechanisms through
      which arthritis-related pain are associated with depression remain unclear. This
      study examined the relationship between arthritis-related pain and depressive
      symptoms to determine if functional impairment and sense of mastery mediated this
      relationship. Participants included 77 African-American and 98 white women with
      arthritis (aged 45-90) who completed structured questionnaires assessing pain,
      functional impairment, sense of mastery and depressive symptoms. Regression
      analyses showed that sense of mastery and functional impairment partially
      mediated the relationship between pain and depressive symptoms for whites such
      that the previously significant pain-depression relationship (beta = 0.40, p <
      0.001) was no longer significant (beta = 0.05, p = 0.62). Only sense of mastery
      partially mediated between pain and depressive symptoms for African Americans.
      Again, the previously significant pain-depression relationship (beta = 0.32, p <
      0.01) was reduced (beta = 0.16, p = 0.19). Implications of the study suggest that
      it is important for service providers and healthcare professionals to be aware of
      different lifetime experiences and perceptions of illness in order to better
      serve the needs of women from different race groups.

PMID- 18807427
TI  - When adults with diabetes attempt to drink less soda: resulting adult-child
      interactions and household changes.
AB  - OBJECTIVE: To examine adult-child interactions related to soda consumption in
      families where 1 inner-city African-American or Latino adult with diabetes is
      attempting lifestyle changes. METHODS: The study used semistructured individual
      interviews of adults and a child (age 10-17) in their home. Interviews were
      audiotaped, transcribed, coded and analyzed for themes. RESULTS: We completed 28
      interviews (14 adult-child pairs). Most adults in this group reduced or stopped
      drinking nondiet soda. Some parents included their children in that change by
      removing nondiet soda from the household and by delivering messages regarding
      soda to their children. Some children obtained soda outside the home. Sweetened
      fruit drinks remained in some households even after nondiet soda was removed.
      Nonetheless, many children reported adjusting to the lack of soda in the
      household and a lower intake of nondiet soda and sweetened fruit drinks, in
      contrast to continued high consumption of sweets and fried food. CONCLUSIONS:
      These in-depth family interviews suggest that interventions intended to change
      adult consumption of sugar-sweetened beverages may also benefit their children,
      and this hypothesis merits further investigation in larger studies. A new
      diabetes diagnosis may motivate adults toward dietary change and provide
      opportunities to improve overall family health. Healthcare providers should
      emphasize decreasing availability of soda for everyone in the home.

PMID- 18807428
TI  - Recruiting African-American barbershops for prostate cancer education.
AB  - Prostate cancer is the most common cause of cancer in men and the second leading
      cause of cancer deaths. African-American men bear a disproportionate burden of
      prostate cancer diagnosis and mortality. Current guidelines for prostate cancer
      screening differ among various medical organizations. Therefore, it is important
      that African-American men have the appropriate information needed to make
      informed decisions about prostate cancer screening. Unfortunately, a large
      percentage of African-American men could potentially be excluded from receiving
      culturally appropriate prostate cancer education. Therefore, a study was designed
      to recruit and intervene with African-American men and barbershops for increasing
      prostate cancer screening decision-making. The purpose of this study was to learn
      effective strategies for recruiting African-American barbershops for prostate
      cancer education and to determine barbershop proprietors' willingness to allow
      their barbershops to be used for research. In this paper, we present the outcomes
      of our recruitment methods for African-American barbershops, including a
      comparative description of participating and nonparticipating barbershops using
      the iMark Data System. One-hundred percent of the surveyed proprietors reported
      that they would allow their clients to learn about prostate cancer. Ninety-six
      percent reported they would consider allowing their clients to have access to
      handheld computers to learn about prostate cancer. We conclude from this study
      that African-American barbershops in general are welcoming environments in which
      to implement community-based prostate cancer education and public health
      research.

PMID- 18807429
TI  - Effectiveness of a premedical postbaccalaureate program in improving medical
      college admission test scores of underrepresented minority and disadvantaged
      students.
AB  - PURPOSE: The purpose of this article is to share the procedures used to
      strengthen the Medical Pathways (MEDPATH) premedical postbaccalaureate program
      (PBP) to increase the chances of its students successfully graduating from
      medical school in four years. METHODS: Subjects included students who
      matriculated into medical school between 1991-1999 (N = 72) following successful
      completion of the 12-month MEDPATH premedical PBP. Students who had passed the
      USMLE Step 1 on the first attempt were defined as successful and were compared to
      those who did not pass on their first attempt. Programmatic changes were
      implemented based on these findings, and outcomes were evaluated. RESULTS: There
      was a significant improvement in total MCAT scores between pre-2003 (PBP entry
      year) participants (Mn = 20.73, SD = 3.10, N = 117) and post-2003 (PBP entry
      year) participants (Mn = 25.27, SD = 2.96, N = 37) (t = 7.86, df = 152, p <
      0.001). MEDPATH premedical PBP coursework grade-point averages improved from 3.48
      to 3.67 over the same time intervals. Diversity of program participants was
      maintained. CONCLUSION: The enhanced MEDPATH premedical PBP appears to be
      producing underrepresented minority and disadvantaged medical students who are
      better prepared to succeed in medical school.

PMID- 18807430
TI  - Reaping what we sow: the emerging academic medicine workforce.
AB  - National efforts to increase diversity of academic medicine faculty led us to
      study the evolution of medical graduates' academic medicine career intentions. We
      conducted a retrospective cohort study of 1997-2004 U.S. allopathic medical
      graduates who completed both the Association of American Medical Colleges'
      Matriculating Student Questionnaire and Graduation Questionnaire, categorizing
      the evolution of academic medicine career intentions (sustained, emerging,
      diminished and no intent) by similarities/differences in graduates' responses to
      the career choice question on both questionnaires. Multivariable logistic
      regression models identified independent predictors of sustained and emerging
      intent (compared with no intent) and diminished intent (compared with sustained
      intent). Of 87,763 graduates, 67% indicated no intent, 20% emerging intent, 8%
      sustained intent and 5% diminished intent to pursue an academic medicine career.
      Asians were more likely and underrepresented minorities less likely to have
      sustained and emerging intent. Women were more likely to have emerging intent.
      Graduates planning more extensive career involvement in research at matriculation
      and reporting greater satisfaction with the quality of their medical education,
      higher clinical clerkship ratings, and lower debt were more likely to have
      sustained and emerging intent and less likely to have diminished intent.
      Graduates planning to practice in underserved areas and choosing family medicine
      were less likely to have sustained and emerging intent and more likely to have
      diminished intent (all p < 0.05). Findings can inform efforts to develop an
      academic medicine workforce that can meet our nation's healthcare needs and more
      equitably reflect the diversity of our society and medical student population.

PMID- 18807431
TI  - Extramedullary myeloid leukemia mimicking lepromatous leprosy.
AB  - Granulocytic sarcoma is an extramedullary localized tumoral lesion of myeloid
      precursors. It is composed of immature cells of the granulocytic series known to
      occur in patients with myelodysplastic syndrome, chronic myelogenous leukemia or
      acute myelogenous leukemia. We present a 29-year-old female who was admitted to
      hospital for lesions that appeared on the face, lips and nose, mimicking
      lepromatous leprosy. It should be kept in mind that granulocytic sarcoma may
      mimick lepromatous leprosy.

PMID- 18807432
TI  - Differences in vitamin-D status may explain black-white differences in breast
      cancer survival rates.

PMID- 18807433
TI  - Racial and ethnic differences in the treatment of seriously ill patients: a
      comparison of African-American, Caucasian and Hispanic veterans.
AB  - BACKGROUND: No national data exist regarding racial/ethnic differences in the use
      of interventions for patients at the end of life. OBJECTIVES: To test whether
      among 3 cohorts of hospitalized seriously ill veterans with cancer, noncancer or
      dementia the use of common life-sustaining treatments differed significantly by
      race/ethnicity. DESIGN: Retrospective cohort study during fiscal years 1991-2002.
      PATIENTS: Hospitalized veterans >55 years, defined clinically as at high-risk for
      6-month mortality, not by decedent data. MEASUREMENTS: Utilization patterns by
      race/ethnicity for 5 life-sustaining therapies. Logistic regression models
      evaluated differences among Caucasians, African Americans and Hispanics,
      controlling for age, disease severity and clustering of patients within Veterans
      Affairs (VA) medical centers. RESULTS: Among 166,059 veterans, both differences
      and commonalities across diagnostic cohorts were found. African Americans
      received more or the same amount of end-of-life treatments across disease
      cohorts, except for less resuscitation [OR = 0.84 (0.77-0.92), p = 0.002] and
      mechanical ventilation [OR = 0.89 (0.85-0.94), p < or = 0.0001] in noncancer
      patients. Hispanics were 36% (cancer) to 55% (noncancer) to 88% (dementia) more
      likely to receive transfusions than Caucasians (p < 0.0001). They received
      similar rates as Caucasians for all other interventions in all other groups,
      except for 161% higher likelihood for mechanical ventilation in patients with
      dementia. Increased end-of-life treatments for both minority groups were most
      pronounced in the dementia cohort. Differences demonstrated a strong interaction
      with the disease cohort. CONCLUSIONS: Differences in level of end-of-life
      treatments were disease specific and bidirectional for African Americans. In the
      absence of generally accepted, evidence-based standards for end-of-life care,
      these differences may or may not constitute disparities.

PMID- 18807434
TI  - Clients' perceptions of the quality of antenatal care.
AB  - OBJECTIVES: To assess perceptions of pregnant women about quality of antenatal
      care. METHODS: Descriptive cross-sectional study in a developing country setting.
      Three-hundred-ninety-five previously booked pregnant women randomly selected from
      private and public health facilities at the 3 levels of care were interviewed
      using a 52-stem interviewer-administered, semistructured questionnaire. The
      questionnaire sought information about bio data, health information and services,
      interpersonal communications, amenities and constellation of services. RESULTS:
      Mean gestational age at booking was 18.5 +/- 6.3 weeks. Only 25.8% of respondents
      booked in the first trimester. Mean number of antenatal visits was 4.0 +/- 2.4.
      Mean time spent during clinic visits was 3.9 +/- 1.4 hours. Waiting time was
      rated as appropriate by most women (67.1%). Women with high education and in
      upper socioeconomic class tended to rate the waiting time as too long. Counseling
      for HIV was the predominant health education subject. More than half (53.9%) of
      respondents did not receive information about cervical cancer. About 10% of
      patients did not receive information about danger signs during pregnancy, breast
      self-examination, family planning and prevention of sexually transmitted
      infections. Clinic amenities and constellation of services were rated highly.
      Most women (96.5%) were satisfied with the care received, would use the same
      facility in future pregnancies and would recommend it to friends. CONCLUSIONS:
      The majority of pregnant women were satisfied with the care they received.
      However, frequent antenatal visits and long waiting times are the norm of our
      antenatal service. Measures for improving elements of quality of antenatal care
      are imperative.

PMID- 18807435
TI  - Comparison of metabolic syndrome variables among pregnant women with and without
      eclampsia.
AB  - BACKGROUND: Similarities in the pathogenesis of pre-eclampsia and metabolic
      syndrome have been described. This study is aimed at determining whether
      metabolic syndrome variables occur in eclampsia. METHODS: Consecutive 45 patients
      with eclampsia were prospectively compared with age, gestational age and parity
      matched women with uncomplicated pregnancy. The main outcome measures included
      plasma lipids, glucose, electrolytes and uric acid levels. RESULTS: The patients
      were predominantly made up of ethnic Hausa primigravidae aged 15-30 years (mean:
      19.5 +/- 4.2 years). As expected, patients with eclampsia had significantly
      higher blood pressure than controls: (systolic 163.0 +/- 24.7 vs. 124.8 +/- 18.1
      mmHg, p = 0.001; diastolic 120.8 +/- 8.7 vs. 79.6 +/- 10.7 mmHg, p = 0.001).
      Compared to the controls, the eclamptics also had significantly higher total
      plasma cholesterol (5.1 +/- 0.7 vs. 4.6 +/- 0.4 mmol/L, p = 0.001), triglyceride
      (1.9 +/- 0.2 vs. 1.7 +/- 0.2 mmol/L, p = 0.01), uric acid (10.4 +/- 2.7 vs. 4.4
      +/- 0.8 mol/L, p = 0.005) and blood glucose (6.3 +/- 2.3 vs. 5.0 +/- 1.0 mg/dL, p
      = 0.01). The risk for intrapartum eclampsia was significantly increased for women
      with hypercholesterolemia [odds ratio (OR) = 6.9; 95% CI: 2.5-20.7]
      hypertriglyceridemia (OR = 5.0; 95% CI: 1.79-14.32) and hyperuricemia (OR = 35.3;
      95% CI: 9.6-14.3). CONCLUSIONS: These results demonstrate that markers of
      metabolic syndrome also exist in this cohort of pregnant women with eclampsia and
      could suggest that both conditions are linked.

PMID- 18807436
TI  - Ventricular fibrillation in a 5-year-old child on therapeutic dose of quinine
      dihydrochloride infusion for acute malaria.
AB  - Malaria is no doubt a disease of public health significance in the tropics.
      Plasmodium falciparum resistant to majority of the first-line antimalarial drugs
      now causes most of the infections treated in sub-Saharan Africa. Although there
      is increasing use of artemisinin-based combination therapy in many African
      nations, quinine still remains a commonly used drug for severe and chloroquine
      resistant malaria. Cardiotoxicity associated with quinine has been largely
      reported. However, this was often more common with toxic doses. This case report
      is on a 5-year-old African Nigerian who was on treatment for uncomplicated
      malaria with quinine dihydrochloride infusion. All the laboratory investigations
      done were within normal limits except for positive blood films for malarial
      parasites. However, pre-treatment electrocardiographic evaluation of the patient
      was not carried out. She developed ventricular fibrillation and died less than
      one and a half hour into the quinine infusion.

PMID- 18807437
TI  - Left ventricular diastolic function in normotensive type-2 diabetic subjects.
AB  - BACKGROUND: Most previous studies on diastolic function in diabetics are
      confounded by coexisting ischemic heart disease, obesity and hypertension.
      Therefore, there may be advantages in studying patients with diabetes mellitus in
      developing nations where confounding variables are less prevalent. The aim of
      this study was to assess the effect of type-2 diabetes mellitus on left
      ventricular diastolic function in normotensive subjects in Nigeria. METHODS: One
      hundred-twenty-two patients with type-2 diabetes mellitus aged 35-74 years with a
      mean age of 55.30 +/- 8.53 years were studied. Patients with blood pressure > or
      =140/90 mmHg or on treatment for hypertension were excluded from the study.
      Ninety-one healthy volunteers aged 40-75 years with a mean age of 55.30 +/- 8.56
      years were recruited as normal controls. Transthoracic echocardiography was
      performed in all subjects to assess their left ventricular diastolic filling
      pattern by analyzing mitral and pulmonary flow velocities. RESULTS: Seventy-one
      (58%) of the type-2 diabetic subjects had evidence of impaired relaxation, 9 (7%)
      had pseudonormal filling and 7 (6%) had a restrictive filling pattern. Only 29%
      of the diabetics had a normal filling profile compared to 58% of the normal
      controls (X2 = 19.4, p = 0.0002). CONCLUSIONS: The result of the study shows that
      Nigerian type-2 diabetics have impaired left ventricular filling compared with
      normal subjects independent of confounding factors such as obesity and blood
      pressure. Therefore, not only Caucasians, African Americans and Asians but also
      African diabetic subjects suffered from diastolic dysfunction.

PMID- 18807438
TI  - Ethical, legal and social issues of genetic studies with African immigrants as
      research subjects.
AB  - There is growing interest in exploring gene-environment interactions in the
      etiology of diseases in immigrants from sub-Saharan Africa. Our experience
      working with the Sudanese immigrant population in Omaha, NE, makes clear the
      pressing need for geneticists and federal and local funding agencies to address
      the ethical, legal and social implications of genetic research with such
      vulnerable populations. Our work raises several questions. How does one design
      research with African immigrant participants to assure it is ethical? Many
      immigrants may not understand the purposes, risks and benefits involved in
      research because of low literacy rates, one of the results of civil wars, or
      concepts of biologic science foreign to their cultures. Is it possible to obtain
      truly informed consent? Do African immigrants perceive genetic research using
      them as subjects as racist? Is genetic research on minorities "biopiracy" or "bio
      colonialism?" In our experience, some Sudanese immigrants have challenged the
      legality and ethics of genetic studies with profit-making as an end. We have
      concluded that it is essential to educate African immigrant or any other non
      English-speaking immigrant participants in research using lay language and
      graphic illustrations before obtaining consent. Cultural proficiency is important
      in gaining the trust of African immigrants; profit-sharing may encourage their
      participation in genetic research to benefit all; involvement of African
      immigrant community leaders in planning, delivery and evaluation using the
      community-based participatory research approach will facilitate healthcare
      promotion, health literacy education, as well as genetic research. It is crucial
      to address the ethical, legal and social implications of genetic studies with
      African immigrants as research subjects.

PMID- 18807439
TI  - Medical students' perspectives on a multicultural curriculum.
AB  - OBJECTIVE: The Liaison Committee on Medical Education requires medical schools to
      deliver curriculum that prepares graduates to care for a culturally diverse
      patient population. This study explores student perceptions of 1 multicultural
      curriculum and their preparedness for dealing with: racism, stereotypes,
      community partnership and disparities. METHODS: Focus groups were conducted with
      22 preclinical and clinical students. Participants were asked semistructured and
      open-ended questions. Using a conceptual approach to thematic content analysis of
      transcripts, the data were reviewed by the study's authors for common themes.
      RESULTS: The authors identified the following: 1) Students asserted that topics
      of multiculturalism, disparities and racism should be incorporated both
      throughout the curriculum and in discrete packages; these topics would be most
      effective if highlighted during their clinical training. 2) Students preferred
      learning about topics such as racism and bias from "real" patients. 3) At times,
      written cases may be counterproductive by reinforcing stereotypes. 4) Finally,
      students note that without recurrent assessment, many students do not perceive
      topics on multicultural issues as vital to their education. CONCLUSIONS: Given
      these recurring themes, we have reviewed our assessment strategies for the
      multicultural curriculum and are implementing a longitudinal assessment of our
      multicultural curriculum. Our findings should inform our school and others as to
      the need for further faculty development and clerkship materials in the area of
      cultural competency.

PMID- 18807440
TI  - Career experiences and perceptions of underrepresented minority medical school
      faculty.
AB  - BACKGROUND: Although studies have outlined the benefit of diversity in academic
      medicine, the number of underrepresented minority (URM) faculty remains low. In
      1998, University of California, San Diego (UCSD) School of Medicine with the
      Hispanic Center of Excellence began a formalized proactive faculty development
      program. Over the past 10 years, recruitment and retention of URM junior faculty
      have increased. We undertook a study to explore factors associated with this
      improvement. METHODS: Semistructured interviews were conducted with 18 out of 26
      URM and 12 out of 26 randomly chosen non-URM assistant and associate faculty
      members throughout 2005. Interview content, based on a conceptual framework from
      Joanne Moody, included career path, knowledge and experience with faculty
      development programs and perceived faculty standing. RESULTS: URM faculty were
      more likely than majority faculty (44% vs. 8%, p = 0.04) to mention the
      importance of a role model in choosing their career path. URM faculty
      participated in faculty development programs at a higher rate than majority
      faculty (78% vs. 17%, p < 0.001), were more likely to find out about programs
      through personal contact (94% vs. 42%, p = 0.001) and reported more personal
      contacts prior to participation (78% vs. 33%, p = 0.02). URM faculty were older,
      graduated earlier and were more likely hired into a staff position prior to
      faculty appointment (61% vs. 17%, p = 0.02). CONCLUSIONS: Academic medical
      centers may find competitive URM candidates in staff positions and alternative
      faculty tracks within their institution. Informing URM faculty often and
      personally about opportunities for faculty development may increase their
      participation in career development programs and improve retention.

PMID- 18807442
TI  - Medical school sexual health curriculum and training in the United States.
AB  - BACKGROUND: With 19 million new sexually transmitted infections (STIs) annually
      and poor screening and counseling by physicians, there is a need to improve
      medical training in sexual health topics in the United States. PURPOSE: To assess
      medical school sexual health curricula through student and faculty descriptions
      of training content, methods and effectiveness. METHODS: Nationwide telephone
      survey of 500 fourth-year medical students (M4s) and medical school curriculum
      offices. RESULTS: Many U.S. medical schools (41/92, 44%) lack formal sexual
      health curricula. Many medical students are uncomfortable taking sexual histories
      from 10-14-year-olds (87/499, 17.4%) and from adults > 75 years (119/498, 23.8%).
      Students who learned history-taking on patients were more likely (OR = 3.22) to
      be comfortable taking histories from 10-14-year-olds than those who did not. Risk
      reduction counseling was considered appropriate by more students than was risk
      avoidance counseling (99.4% vs. 74.2%, P < 0.001). CONCLUSION: There are
      significant deficiencies in medical students' training on sexual health.

PMID- 18807441
TI  - Educating older African Americans about the preventive importance of routine
      comprehensive eye care.
AB  - Older African Americans have higher rates of vision impairment and lower
      utilization rates of comprehensive eye care, compared to Caucasians. InCHARGE is
      an eye health education program for this population that promotes prevention
      through the annual, dilated comprehensive eye examination. This study, using a
      pre-/postdesign, evaluated whether InCHARGE imparted knowledge about prevention
      and strategies for reducing barriers to care. The program was presented to 85
      older African Americans in 5 senior centers in Montgomery, AL. Changes in
      attitudes about annual eye care were assessed by a questionnaire before and 3
      months after InCHARGE. At baseline, most (> 85%) responded it would not be
      difficult for them to find an ophthalmologist or optometrist, and the exam cost
      was not a problem. Twenty-five percent reported problems finding transportation
      to the doctor and covering the eyeglasses cost. Forty-four percent reported not
      having an eye exam in the past year; 13% reported not having one within 2 years.
      Three months after InCHARGE, those who reported that they could find a way to get
      to the doctor increased (X2 = 3.8, p = 0.04). After InCHARGE, 72% said they
      either had received or scheduled an eye exam. Responses to a question about what
      was learned from InCHARGE indicated that the InCHARGE's key messages about
      comprehensive eye care were successfully imparted to most. This study suggests
      that older African Americans in the urban south have positive attitudes about eye
      care, even before an eye health education presentation. Following InCHARGE, they
      identified transportation problems less frequently as a barrier, indicated that
      they learned InCHARGE's key message and had plans for seeking routine, preventive
      eye care. A next step is to verify through medical record review the extent to
      which the high rates of self-reported eye care utilization reflect behavior.

PMID- 18807443
TI  - Coronal curing depth of two dual-cure, methacrylate-based endodontic sealers.

PMID- 18807444
TI  - The operating microscope: a unique tool in endodontology.

PMID- 18807445
TI  - Radiographic documentation for post perforation.

PMID- 18807446
TI  - The twisted file: a new paradigm in endodontic shaping.

PMID- 18807447
TI  - Distraction osteogenesis and orthodontic therapy in the treatment of
      malpositioned osseointegrated implants: a case report.
AB  - Resorption of the residual alveolar ridge often hinders ideal implant placement.
      In some cases, vertical bone loss causes the implant to be positioned more
      apically, resulting in aesthetic and biomechanical complications, as well as
      elongated clinical crowns as the outcome of treatment. This case presentation
      demonstrates a surgical technique that allows the use of distraction osteogenesis
      in combination with conventional orthodontic treatment to three-dimensionally
      reposition an implant-bony segment into a more favorable aesthetic and
      biomechanical position, thus improving the crown-to-implant ratio and leveling
      the gingival contours with those of the adjacent teeth.

PMID- 18807448
TI  - A magnified look at visualization: applying today's technology for improved
      efficacy.

PMID- 18807449
TI  - Preparation design and considerations for direct posterior composite inlay/onlay
      restoration.
AB  - In order to ensure a functional, aesthetic, and long-lasting porcelain result,
      clinicians need to anticipate the strengths and limits of the restorative
      material, as well as the specific requisites of the presented case. As flaws in
      preparation design can have significant and detrimental effects on the final
      result, clinical comprehension of the dimensions and limitations during this step
      is of utmost importance. This article discusses a case presentation in which
      porcelain restorations were placed for two adjacent teeth. Although the clinician
      anticipated placing inlay or onlay restorations, the degree of decay and the
      location of hairline fractures would necessitate prophylactic removal of a
      weakened or undermined cusp.

PMID- 18807450
TI  - Aesthetic and conservative dentistry.

PMID- 18807451
TI  - Minimally invasive dentistry: a treatment philosophy.

PMID- 18807452
TI  - The role of the oral health professional in tobacco cessation.

PMID- 18807453
TI  - The Er,Cr:YSGG laser periodontal surgery.

PMID- 18807454
TI  - Treatment of isolated recession defects using the lateral sliding flap: a case
      series.
AB  - Root coverage using the lateral sliding flap technique presents many potential
      benefits to patients with localized recession defects. By using the tissue
      adjacent to the recession defect, the lateral sliding flap allows for correction
      of the defect without the discomfort encountered during other grafting techniques
      associated with palatal donor sites. This procedure is a time efficient, less
      invasive, and highly aesthetic treatment option for managing isolated recession
      defects. The following case series describes this technique and demonstrates its
      efficacy in various clinical settings.

PMID- 18807455
TI  - The integrated CAD/CAM office.

PMID- 18807456
TI  - [De novo geriatric, Cicero, and the new and better aging process].

PMID- 18807457
TI  - [Evaluation of life in the elderly (LWO): the validation of a measuring
      instrument].
AB  - The goal of this study is the adaptation and validation of the Dutch translation
      of Lawton's "Valuation of Life" scale. In developing this scale Lawton et al.
      argued that the usual health related quality of life scales had a limited
      contribution in explaining health utility and desired length of life and that the
      "Valuation of Life" is intended to cover a specific quality of life domain not
      related to health. The translated scale has been implemented in the 4th
      observation of the Longitudinal Aging Study Amsterdam (LASA) in 2001-2002. In
      total 1139 respondents between 65 and 95 years old reacted to the written
      questionnaire. After extensive structural analyses of the data we concluded that
      the Dutch version of the scale could be reduced from the original 19-item to a 12
      item scale. In addition this scale could be divided in three 4-items-subscales,
      clearly labelled as Resilience, Ambition and Vitality. The new scale as well as
      the subscales hardly overlap with the data of two health related quality of life
      scales while the overlap with the more or less objective health measures
      (discriminant validity) remains limited. It appears that the Dutch "Valuation of
      Life" scale is to a certain extend related to other positive affect measures as
      Self evaluation, Mastery and Self-efficiency (concurrent validity). For the
      moment we agree that the Dutch scale measures an important and specific domain of
      quality of life without any reference to health issues in the scale. Whether
      these data contribute in explaining health utility and desired length of life
      remains to be demonstrated in another publication.

PMID- 18807458
TI  - [Radio frequency ablation therapy in the elderly breast cancer patient].
AB  - Breast cancer is an important health care problem, especially in the increasing
      elderly generation. Treatment of these fragile patients is a challenge for the
      clinician. Undertreatment has been linked to a higher percentage of recurrence
      and cancer related morbidity, while overtreatment leads to treatment related
      morbidity and mortality. Minimally invasive techniques do offer new opportunities
      for patients, who are no candidates for conventional surgery. The tumor lesion is
      treated locally and selective with minimal damage to surrounding tissue, yielding
      an adequate local tumor control. Radio frequency ablation technique seems an
      effective and safe method for treatment of the elderly patient with small (< 3
      cm) breast cancer.

PMID- 18807459
TI  - [Infectious diseases in Poland in 2006].
AB  - Over last decade problem of infectious diseases in Poland remains stable with
      trends of decreasing incidence of most reported infectious diseases. In
      particular there was observed decrease in incidence of tuberculosis and foodborne
      infections causes by Salmonella sp. On the other hand it was observed increase of
      reported foodborne infections caused by Campylobacter and Yersinia as well and
      viral ones caused by noroviruses and rotaviruses. Despite marked increase of
      diagnosed and reported cases sensitivity of reporting of those infections remains
      unacceptably low. Reported incidence of HIV infections remains relatively stable
      over last years. But increased fraction of heterosexually transmitted cases
      points to the problem of increased incidence out of so called "risk groups" among
      the general population. It was also noted worrisome increase of incidence of
      syphilis. The highest incidence was noted regarding influenza and other upper
      respiratory tract infections. Low level of vaccinations against influenza remains
      the problem which requires continuous health promotion efforts. The best
      epidemiological situation was observed among vaccine preventable diseases, which
      reflects effectiveness of vaccination program. Though widening of our program
      into several important infections included in vaccination programs of other EU
      countries would be needed in oncoming years. Infectious diseases caused 0.70% of
      deaths. Mortality from infectious diseases was 6.8/100,000 and was significantly
      higher among men (8.8) then among women. (5.0). In urban settings mortality from
      infectious diseases was higher (7.4/100,000) then in the country (5.8). In
      particular districts (voivodeships) mortality indices remained in the range of
      5.2 (podlaskie) to 9.7 (slaskie). The highest number of deaths was caused by
      sepsis (41.1%, without neonatal sepsis).

PMID- 18807460
TI  - [Measles in Poland in 2006].
AB  - In Poland 120 measles cases were registered in 2006 (0.31 per 100,000
      population). It was a substantial increase, compared to the years 2002-2005, when
      the number of locally-acquired cases was inferior to 1 case per 1 000 000
      inhabitants. Three cases were linked to a large Ukrainian outbreak, including the
      2006 index case on the Polish territory. Out of 106 cases with vaccination
      history available, 62 (58%) were not vaccinated, 26 (25%) were fully vaccinated
      (including 16 laboratory confirmed), and 18 (17%)--incompletely vaccinated. The
      most affected age groups were children under 2 years of age (incidence 2.62 per
      100,000 population), 5-year olds (1.08), and adults aged 25-29 years (1.09). In
      20 cases complications were seen, including pneumonia (n = 10) and otitis media
      (n = 6). 75 measles cases (63%) were hospitalized, no deaths were recorded. The
      2006 outbreak lead to a substantial improvement of measles surveillance
      performance. Two hundred eighty-nine suspect cases were reported, of which 252
      (89%) were tested serologically for measles. Additionally, molecular testing of
      suspect cases was introduced in 2006. The first isolated virus strains belong to
      the D4 and D5 genotypes, not related to the Ukrainian outbreak. In order to
      properly document measles elimination during following year, high sensitivity of
      rash-like illness surveillance should be maintained, and isolation of viral
      strains from each chain of infection should be attempted.

PMID- 18807461
TI  - [Mumps in Poland in 2006].
AB  - In 2006, 15,115 cases of mumps were reported in Poland. The incidence (39.6 per
      100,000) was considerably lower compared to 2005 (188.5) and to the median
      incidence in 2000-2004 (104.6). The decrease of mumps incidence in 2006 is
      related to high coverage of routine two-dose immunisation against measles, mumps
      and rubella, maintained since its implementation in 2003. Children 5-9 year old
      were the most affected age group (incidence 328.7 per 100,000). Since the
      immunisation schedule during 2003-2006 involved administration of MMR doses at
      the ages of 2 and 10 years, a stable decrease of mumps incidence is expected
      after routine immunisation will cover the school age birth cohorts (6-14 year
      olds). Of 15,115 cases, 656 (4.3%) were hospitalized and no deaths attributed to
      mumps were reported.

PMID- 18807462
TI  - [Rubella in Poland in 2006].
AB  - In Poland, 20,668 cases of rubella were registered in 2006 (incidence 54.2 per
      100,000 population), of which 103 (0.5%) cases were laboratory confirmed, and 173
      (0.8%) were confirmed based on the epidemiological link with laboratory confirmed
      cases. The remaining 98.7% were reported based on clinician's diagnosis. No cases
      of congenital rubella syndrome were reported. In 2006 a 1.6-fold increase in
      incidence was noted, compared to 2005. As in 2005 rubella incidence among
      residents of urban areas was lower, compared to residents of rural areas (43.6
      and 71.0 respectively). The incidence in men (68.5) was 67% higher than in women
      (40.8). The highest incidence was observed in children aged 8 and 9 years (468.6
      and 488.1, respectively). Approximately 0.37% of cases required hospital
      admission. No rubella deaths were registered. Only 276 cases (1.3%) were
      confirmed either serologically or by epidemiological link to a laboratory
      confirmed case. An improvement in diagnostic certainty of reported is necessary
      to assess the impact of 2-dose immunization implemented in 2003 on rubella
      epidemiology in Poland.

PMID- 18807463
TI  - [Influenza in Poland in 2006].
AB  - A total number of 251,815 cases of influenza and influenza-like illness
      registered in Poland in 2006 (incidence 660.4 per 100,000 population). Regionally
      the incidence varied from 75.6 per 100,000 in swietokrzyskie voivodeship to
      1,690.4 in mazowieckie. The highest reported incidence was observed in age group
      0-4 years (1,543.1 per 100,000). Children and adolescents under 15 years of age
      accounted for 34.3% of all cases (age specific incidence 1,434.8 per 100,000). In
      this age group the incidence varied regionally from 190.2 in lubuskie voivodeship
      to 3,582.5 in lodzkie. 284 patients (0.11% of all cases) required hospital
      admission. There were 14 deaths due to influenza, in 71.4% these were persons
      over 70 years of age. In the epidemic season 2005/06 infections with influenza
      virus registered in Poland were mainly caused by type B similarly to other parts
      of Europe. Thirty five influenza strains were isolated, including 6 strains of
      subtype A/H1, 2 strains of subtype A/H3 and 27 strains of type B. All of these
      isolates with the exception of one strain of influenza B were antigenically
      similar to the vaccine strains recommended for the epidemic season 2005/06.

PMID- 18807464
TI  - [Pertussis in 2006].
AB  - In 2006 number of reported cases of pertussis in Poland was 1520, 21% less then
      in the previous year (1925 in 2005). Slightly higher incidence was among females
      (846 cases, 4,3/100 000) than among males (674 cases, 3,7/100 000). In urban
      areas incidence was significantly higher 1185 cases (5,1/100 000) than in the
      rural ones 335 (2,3/100 000). Incidence in urban areas was higher in all age
      groups. In general number of cases reported in Poland remains relatively low.
      Problem is uneven distribution in different voivodeships (districts) which bring
      strong possibility of very low sensitivity of surveillance in some regions.

PMID- 18807465
TI  - [Scarlet fever in Poland in 2006].
AB  - In total 10,649 cases were registered (7.4% more then in 2005) corresponding to
      the incidence of 27.9 per 100,000 population. Regionally the incidence ranged
      from 12.6 per 100,000 in podlaskie voivodeship to 57.4 in dolnoslaskie
      voivodeship. As observed previously incidence in the urban areas (31.3) was
      significantly higher than in the rural areas (22.6) and the incidence in men
      (31.2) exceeded the incidence in women (24.8). The majority of cases occurred in
      children and adolescents younger than 15 years (mode - 6 years; incidence 449.9.
      Approximately 1.2% of cases were hospitalised. There were no deaths due to
      scarlet fever reported in 2006.

PMID- 18807466
TI  - [Meningitis and encephalitis in Poland in 2006].
AB  - In Poland, 3 693 cases of neuroinfections were reported in 2006, of which 989 had
      bacterial aetiology, 1 874--viral aetiology, and 512--other or unknown origin.
      The etiological agent was determined in 455 (46%) cases of bacterial
      neuroinfections. Among them Neisseria meningitidis was found in 148 cases,
      Haemophilus influenzae type B (Hib) in 39 cases and Streptococcus pneumoniae in
      119 cases. An increasing trend in meningococcal infections incidence has been
      observed in 2006, and a substantial decrease of Hib incidence, related to
      increasing vaccination coverage. Viral neuroinfections incidence in 2006
      increased compared to year 2005. Etiological factors of central nervous system
      aseptic infections were established only in minor proportion of cases--3% of
      meningitis and 20% of encephalitis. Among confirmed cases, there were 317 cases
      of tick-borne encephalitis and 31 cases of herpetic encephalitis. Tick borne
      encephalitis incidence increased in 2006 (0.83), compared to 2004 - 2005. Most of
      the cases were reported from endemic areas of north-eastern part of the country.

PMID- 18807467
TI  - [Legionellosis in Poland in 2006].
AB  - In 2006 the 89 cases and in 2005 the 21 cases of legionellosis were reported in
      Poland, the incidence rate was respectively 0.23 and 0.055/100 000. Legionellosis
      is a notified disease in Poland since 2002, but laboratory diagnostic methods
      were introduced even earlier, in 1997. The increasing trend in incidence rate was
      due to an active cooperation with some hospital staff and financial support from
      Polish Committee of Research Activity. The first time nosocomial Legionella
      infections were observed in Poland. The outbreak occurred among patients of
      ophthalmic ward. Five cases with pneumonia were examined by laboratory methods:
      for two the diagnose was confirmed, for two were presumptive, for one was not
      confirmed. Three persons died (two with diagnose presumptive, one with
      confirmed). Every registered case was laboratory examined in National Institute
      of Hygiene, the only place where laboratory tests were performed. Most of the
      cases were diagnosed with serological tests--determination with ELISA test the
      anti-legionella antibodies in IgM fraction as the most recent answer for
      Legionella infection, few by detection of legionella antigen in urine. All BAL
      specimens from several patients were negative when examined with culture method,
      but some were positive with PCR only. Since 1987 to 2006 the 17 foreign tourists
      were registered in EU countries as probably infected in Poland. Epidemiological
      investigation with the examination of water system for Legionella sp., cleaning
      and disinfection (if needed) was done in suspected hotels.

PMID- 18807468
TI  - [Dysentery and amoebiasis in Poland in 2006].
AB  - The number of notified as shigellosis, bacillary dysentery cases in the three
      last years (2004, 2005, 2006) is lower and lower and is the lowest of all years
      since 1918 when notification started. Only 35 cases were notified in the year
      2006, while 80 were notified in 2005 (incidence rate 0.21/100 000 population),
      and 74 cases in 2004 (incidence rate 0.19/100 000 population). No one-death case
      was notified. The last three death cases were notified in 1999. No one outbreak
      was registered. Twelve cases got infection while being abroad. S. flexneri was
      found only in 41% of with shigellosis patients and 60% of infected food handlers,
      S. sonnei was dominating, isolated from 59% of patients and from all contacts and
      carriers but only from 40% of healthy food handlers examined. Two cases of S.
      boydii infections were found. Such structure of etiology is indicating that only
      few cases among children and young persons were diagnosed. In the period of low
      frequency of Shigella infections, the external quality assessment control of the
      quality of bacteriological media, laboratory and prae-laboratory procedures for
      detection of different Shigella groups and types should be executed. The
      increasing number of amoebic dysentery was registered: 21 cases in 2006 incidence
      rate 0.05/100 000 but only 2 cases in 2005. The cases were registered in 8 out of
      16 voivodeships probably imported from underdeveloped countries. It is a new
      emerging problem.

PMID- 18807469
TI  - [Foodborne infections and intoxications in Poland in 2006].
AB  - A total of 17 157 bacterial foodborne infections and intoxications were
      registered in 2006 (incidence 45/100 000 population). Unlike bacterial
      infections, the incidence of viral foodborne infections increased in the recent
      years (2006 - 54.21 vs. 2005 - 32.8, 2004 - 27.2, 2003 - 21.1 and median 1998
      2002 - 10.0). The parasitic foodborne infections did not change much during the
      recent years. There were 11 deaths related to foodborne infections or
      intoxications registered in 2006, of which the following etiologic agents were
      established: Salmonella Enteritidis (4), other bacteria (4), other virus (1) and
      E. multilocularis infestation (2). In 2006 were notified of 385 foodborne
      infections and intoxications involving 6839 cases (only outbreaks involving 4
      person or more) and 170 foodborne (involving 2-3 persons). S. Enteritidis
      were/was the most frequency etiological agent in outbreaks ((51.2% of outbreaks,
      39.8% cases in outbreaks). The main vehicle of foodborne outbreaks in 2006 were
      food prepared from milk and eggs (26.0% of outbreaks, 16.1% cases in outbreaks)
      and meals various (> 3) raw materials of animal sources (22.5% cases in
      outbreaks). Private homes prevailed among places the places of food contamination
      (17.4% of outbreaks). In 2006 the seven epidemics with 100 or more cases each,
      were registered involved 953 cases.

PMID- 18807470
TI  - [Yersiniosis in Poland in 2006].
AB  - This is the first annual epidemiological report on yersiniosis in Poland. In our
      country yersiniosis has been reported since 2003. The total number of 140
      yersiniosis cases were reported in 2006 in Poland. The incidence rate was 0.37
      per 100,000 population. In this year 111 cases of enteric yersiniosis and 29
      cases of extra intestinal yersiniosis were notified. The most frequent clinical
      manifestation of extraintestinal yersiniosis was joints inflammatory. No death
      and outbreak were reported. About seventy percent of patients were hospitalized.
      The serotype was determined for 43 isolated strains of Yersinia enterocolitica.
      Most of them was serotype O3 Yersinia enterocoolitica--39 cases. The most
      important finding was the occurrence of cases caused by serotype O8 Yersinia
      enterocolitica in our country.

PMID- 18807471
TI  - [Campylobacteriosis in Poland in 2006].
AB  - This is the first annual epidemiological report on campylobacteriosis in Poland.
      The total number of 157 campylabacteriosis cases were reported in 2006 in Poland.
      The incidence rate was 0.41 per 100 000 population. No death was reported. About
      56% of patients were hospitalized. Despite the fact that since 2003, the
      reporting of campylobacteriosis has been mandatory in Poland, data about
      Campylobacter infections are restricted to some regions of the country. This is
      mostly due to the limited number of laboratories performing the diagnosis of
      Campylobacter. The species of Campylobacter was determined in 129 cases (82%):
      105 cases (67%) were caused by C. jejuni infection and 24 by C. coli. In 2006
      three outbreaks were reported in Poland, all were considered family outbreaks.
      Two of these were caused by C. jejuni and one by C. coli.

PMID- 18807472
TI  - [Salmonellosis in Poland in 2006].
AB  - In 2006, 13 362 salmonellosis cases were reported (16 006 in 2005), the incidence
      rate was 35.0 per 100 000 population. In total 298 outbreaks were reported
      involving 2 965 cases. The most common type of outbreaks were households
      outbreaks. Over seventy percent of patients were hospitalized, however the
      hospitalization rate was higher for extraintestinal manifestations--94.7%. As in
      previous years the seasonal peak was observed in July and August. The most
      frequently isolated type remained Salmonella Enteritidis--over 80% of cases. Only
      four other serotypes (Typhimurium, Hadar, Infantis and Virchow) were detected in
      all voivodeships. The age, gender, and urban/rural distributions of salmonellosis
      are similar to the distributions observed in previous years. Children aged 2 are
      the most affected age group (incidence 391.6 per 100 000 population).

PMID- 18807473
TI  - [Botulism in Poland in 2006].
AB  - A total number of 50 foodborne botulism cases were registered in Poland in 2006
      (incidence rate 0.13 per 100,000 population), in rural areas--34 cases (incidence
      0.23) and in urban areas--16 cases (incidence 0.07). There were 35 sporadic
      cases, 4 outbreaks of two persons and one outbreak involving three and four
      persons. Tinned meat (especially home made) were the main vehicle of botulin
      toxin. Two deaths from foodborne botulism were registered.

PMID- 18807474
TI  - [Hepatitis B in Poland in 2006].
AB  - A total of 1,693 of hepatitis B cases (including 59 cases of co-infections with
      HCV) were reported in Poland in 2006, with incidence rate 4.4 per 100,000
      population. Regionally the incidence varied from 1.7 per 100,000 in lubuskie
      voivodeship to 10.5 in lodzkie. In total number of registered cases 70% were new
      chronic ones (incidence 3.1 per 100,000; regionally ranged from 0.4 in podlaskie
      voivodeship to 8.8 in lodzkie), and only 30% acute cases (incidence 1.3;
      regionally ranged from 0.6 in zachodniopomorskie voivodeship to 2.1 in slaskie).
      The highest reported incidence (both acute and chronic) was observed in age group
      35-39 years (6.3 per 100,000) but the highest incidence of chronic form was among
      15-19 (4.8) years old and acute form among 60-64 years old (2.4). The total
      incidence in the urban areas (4.8) was higher than in rural areas (3.8) and also
      was higher in men (6.0) than in women (2.9). This situation we could observe in
      previous year. In total 68.3% of patients were hospitalized and the percentage
      varied regionally from 39.5% in lubelskie voivodeship to 100.0% in podkarpackie.
      There were 64 deaths attributed to hepatitis B in 2006 including 8 deaths of
      acute and 56 of chronic hepatitis B.

PMID- 18807475
TI  - [Hepatitis C in Poland in 2006].
AB  - In 2006, with 2949 new cases of hepatitis C, the incidence (7.7 per 100 000) was
      within the range observed in the last year (2997 new cases with the incidence
      rate 7.9 in 2005). There were 131 deaths due to hepatitis C. The cause of death
      in 125 cases was chronic stage of hepatitis C and the other 6 deaths were the
      result of the acute hepatitis C. In 2006, data on all cases of newly detected HCV
      infections (past or present) are also included in the analysis of epidemiological
      situation of hepatitis C in Poland. The number of cases of newly detected
      infection reported was 8952, which corresponds to the rate of detecting HCV of
      23,5 per 100 000 population. Hepatitis C becomes a major health problem in
      Poland.

PMID- 18807476
TI  - [Tetanus in Poland in 2006].
AB  - Number of cases of tetanus in Poland remains low. In 2006, 22 cases of tetanus
      (13 women and 9 men) were reported in Poland. 17 of those cases were among people
      of age 50 or more. In 2006 6 deaths were reported, all of them among people older
      then 59 years. In 17 cases vaccination status was unknown. 4 cases were
      unvaccinated, 3 received buster dose of vaccine less then 10 years before
      infection. Post exposure anatoxine was applied only in case. The data show
      effectiveness of vaccination program in younger age groups, but they also show
      need for promotion of post exposure prophylaxis, especially among older people
      both in rural and in urban areas. No case of neonatal tetanus was noted in Poland
      since 1984.

PMID- 18807477
TI  - [Rabies in Poland in 2006].
AB  - In Poland 81 cases of animal rabies were reported in 2006. Since 1993, when mass
      oral vaccination of wild animals against rabies was introduced in our country, a
      positive impact of fox immunisation has been visible on the epizootic situation
      of rabies in Poland. In 2006 we observed almost forty-fold decrease in number of
      animal rabies cases in comparison with the year 2001. Sources of wild and
      domestic animal rabies are still present, mainly in the east part of the country
      (80% of rabies cases). In Poland out of 7 225 people vaccinated against rabies,
      99 (1.3%) were bitten by or had contact with a rabid animal. The main reason for
      vaccination against rabies was exposure to an animal with not excluded rabies (6
      502 cases, 90%) or animals healthy at the moment of the exposition (624 cases,
      8.6%).

PMID- 18807478
TI  - [Human brucellosis in Poland in 2005 and 2006].
AB  - In 2005--5 cases of human brucellosis in Poland were reported. One domestic case
      comprises chronically ill professional who in the past was involved for many
      years in the control of animal brucellosis. All cases of acute infection (4
      cases) were imported from endemic areas. In 2006 no case of human brucellosis in
      Poland was reported.

PMID- 18807479
TI  - [Trichinellosis in Poland in 2006].
AB  - In the year 2006 in Poland a total of 130 cases of human trichinellosis were
      registered, 5 of which were individual cases. The remaining cases occurred in
      seven outbreaks. Two outbreaks were large and involved 257 exposed people of
      which 104 became ill. The source of the infection in most of the outbreaks was
      wild boar meat. In 2 outbreaks the infected products were prepared from pork and
      wild boar meat and in one of the outbreaks only from pork. The presence of
      Trichinella endemic areas in Poland determines the necessity of careful meat
      inspection for Trichinella spp.

PMID- 18807480
TI  - [Cestode infections in Poland in 2006].
AB  - In the year 2006, 158 intestinal cestode infections were registered in Poland.
      Among them 97 were caused by Taenia saginata, 4 by T. solium, 39 by Taenia sp., 1
      by Diphyllobothrium latum. Moreover, 65 cases of cystic echinococcosis were also
      registered. The obtained results confirmed decreasing frequency of intestinal
      cestodoses in Poland.

PMID- 18807481
TI  - [AIDS and HIV infection in Poland in 2006].
AB  - The cumulative number of AIDS cases diagnosed in Poland in 1986 to 2006 reached
      1929, and 855 AIDS deaths were registered during this time. In recent years a
      minor upward trend in AIDS incidence is observed with the highest numbers of
      incident cases in 2004- 175 (incidence 0.46 per 100,000) and 2006 -156 (0.41 per
      100,000). The number of reported deaths decreased from 64 in 2005 to 44 in 2006.
      Taking into account the official life statistics data, AIDS deaths might be
      underreported. In 2006, with 750 newly detected HIV infections, the incidence
      (2.0 per 100,000) was higher than observed during recent years. Injecting drug
      users constituted the most numerous risk group both among the AIDS cases (51.9%)
      and the HIV infection cases (15.2% of all cases and 52.5% of cases with known
      transmission route). In 2006 the infection was diagnosed in 15 children of
      infected mothers. The proportion of reports of HIV infections with missing
      information on the risk group though remained very high (71.1% of all 2006
      reports). In order to monitor the epidemiological situation better quality of
      data will need to be assured.

PMID- 18807482
TI  - [Malaria in Poland in 2006].
AB  - There were 19 cases of malaria meeting European Union case definition for
      confirmed case registered in Poland in 2006. All of them were imported, including
      1 case of relapse: 17 from Africa, 1 from Asia and 1 from Oceania. Species of
      Plasmodium was determined for 12 cases (68%): P. falciparum in 12 cases and P.
      vivax in one. There were 15 cases in males and 4 in females. Age at onset ranged
      from 17 to 59 years and a considerable number of cases occurred in persons 50
      years old or older (5.26%). Common reasons for travel to endemic countries
      included tourism or family visits (10 cases) and professional or missionary
      travel (5 cases). Only four cases used chemoprophylaxis and the relevant
      information was missing in 4 cases. In two cases of malaria caused by Pl.
      falciparum the clinical course was severe and one of them died.

PMID- 18807483
TI  - [Tuberculosis in Poland in 2006].
AB  - Tuberculosis has been a major health problem in Poland for many years. In 2006 y.
      decrease of tuberculosis notification rates in Poland has continued. In this year
      8593 tuberculosis cases notified, incidence rate was 22.5 per 100.000 population
      with the large differences in notification rates between voivodships / region
      from 11.0 in the West to 36.0 in the East. The incidence in 2006 was 7.4% lower
      than in previous year and 38.0% lover than in 1997 y. Pulmonary cases represented
      91.7% of all TB cases of which 61,2% were bacteriologically confirmed. Low
      proportion--8.3% extrapulmonary TB cases which continues for many years may
      indicates inadequacies in diagnosis and registration of this form. Children TB
      cases--69 incidence 1.1--represented 0.8% of all TB cases notified in Poland. The
      incidence of tuberculosis increases with age from 1.1 in children to 42.8 among
      65 and older. The median age group--50-54. The incidence of men 30.9 is two times
      higher than in women--14.7 and in rural population higher than in urban
      respectively 23.4 and 22.0. Among of all TB pulmonary cases were 279 cases--about
      3.5% all TB cases--with resistance to at least one drug. In these cases were 54
      MDR TB cases. In overall registered cases were 33 cases among HIV/AIDS patients
      and 47 cases among foreigners. There were 806 deaths due to tuberculosis: from
      tuberculosis pulmonary 777--and 29 from extrapulmonary tuberculosis reported in
      2005 i.e. 2,1 per 100.000. Mortality among males 3.4 was four times higher than
      among females--0.9. Among all deaths from tuberculosis--44% were in patients 65
      year of age and older. Since many years the TB mortality is of the order of 0.2%
      of total mortality and more than 1/3 of all deaths from infectious diseases.
      CONCLUSIONS: In last decade decrease incidence of TB has continued. The incidence
      of tuberculosis in Poland was about two times higher than mean incidence before
      enlargement European Union (15 countries). The distance between Poland and EU
      countries with lowest incidence TB is estimated 20-25 years.

PMID- 18807484
TI  - [Polish Experts Group on HBV. Therapeutic recommendations on 2008 year
      (antiretroviral treatment of chronic hepatitis B)].

PMID- 18807485
TI  - [Current opportunities for treatment of chronic hepatitis C in patients with HIV
      co-infection].
AB  - Liver diseases, mainly chronic viral hepatitis, recently have become the main
      cause of hospitalization and death in individuals with HIV infection. As HCV
      infection is predominant condition in this group of patients, treatment of
      hepatitis C is extremely important in halting hepatic injury. Large clinical
      trials (APRICOT, RIBAVIC, ACTG 5071) showed satisfactory efficacy and safety of
      therapy with pegylated interferon alpha and ribavirin. Other trials, searching
      ways to improve efficacy of chronic hepatitis C treatment in HIV co-infected
      individuals, are still running. Management possibilities include higher doses of
      ribavirin and, prolonged course of treatment. The article summarizes current
      state of knowledge in the field of chronic hepatitis C treatment in HIV/HCV
      coinfected individuals.

PMID- 18807486
TI  - [Fluorescence of age in serum in detecting liver cirrhosis and hepatocellular
      carcinoma among patients with anti-HCV antibodies].
AB  - OBJECTIVE: To evaluate usefulness of total fluorescence of advanced glycation end
      products (AGE) and haptoglobin (Hp) measurement in human serum as parameters in
      liver cirrhosis and hepatocellular carcinoma development among patients with anti
      HCV antibodies. MATERIALS AND METHODS: 43 patients (20 women and 23 men) with
      chronic hepatitis HCV were examined (14 individuals with liver cirrhosis and 9
      with primary liver cancer). The control group numbers 20. As reflection of AGE
      concentration, total fluorescence in serum samples was measured with
      spectrofluorimetric method and haptoglobin with microplate guaiacol test.
      RESULTS: We affirmed that total fluorescence in examined groups was higher than
      in healthy subjects, but increase was not statistically significant. Fluorescence
      of AGE in serum from patients with hepatocellular carcinoma was lower in
      comparison to patients with cirrhosis and anti-HCV carriers. Haptoglobin was
      significantly decreased in serum of cirrhosis patients as compared to HCV
      carriers of patients with hepatocellular carcinoma (p < 0.001). CONCLUSIONS: The
      measurement of total fluorescence AGE is not differentiating for liver cirrhosis
      and hepatocellular carcinoma among anty-HCV carriers. We confirmed that
      haptoglobin, parameter included in fibrotest, is very useful, in detecting liver
      cirrhosis.

PMID- 18807487
TI  - [Metalloproteinases in meningoencephalitis].
AB  - Meningoencephalitis remains a devastating disease with high morbidity and
      mortality. Despite advances in antibiotic treatment and critical care, mortality
      rate in bacterial meningoencephalitis is close to 25%. Moreover, neurological and
      neuropsychological sequelae emerge in up to 50% of survivors. Adverse outcome is
      significantly associated with events secondary to meningitis and damage of the
      blood-brain barrier. Several studies conducted on animals confirmed that matrix
      metalloproteinases (MMP), a family of enzymes with major actions in the
      remodeling of exracellural matrix components facilitate this process which
      results in acute neurological complications. Gelatinases (MMP-2, MMP-9), the most
      complex family member, through degradation of gelatine and collagen IV play an
      important role in the pathogenesis of brain's inflamatory diseases (e.g. Guillian
      Barre syndrom) and contribute to spreading the disease beyond the central nervous
      system. Infection (bacterial, viral or fungal) can lead to increased
      concentration and activity of metalloproteinases due to excessive enzyme's
      secretion or decrease in level of its natural inhibitors. A detailed analysis of
      those enzymes could help in developing new diagnostic and prognostic markers for
      meningoencephalitis and could facilitate new treatment approaches.

PMID- 18807488
TI  - [Toxocariasis in children--difficult clinical problem].
AB  - Toxocariasis in humans is a zoonosis due to the migration of Toxocara canis or T.
      cati larvae in human body. This review provides basic information on pathology of
      infection and clinical signs and symptoms of toxocariasis in children. The cases
      diagnosed in the recent years in central Poland are presented. The disease was
      recognised accidentally based on the results of laboratory analysis performed for
      other reasons, when abnormalities suggesting an active helminthiasis were found
      (eosinophilia, elevated IgE level and/or anemia). The high rate of soil
      contamination in households of the patients demonstrated elevated risk of
      infection and reinfection in both, rural and urban areas. Presented data show the
      need for educational programs which should be implemented for prevention of
      Toxocara infection in children.

PMID- 18807489
TI  - [Prevalence of HCV, HBV and HIV infections among severe Polish haemophiliacs].
AB  - In the past, haemophilia replacement therapy was based on fresh frozen plasma,
      cryoprecipitate and blood transfusions--i.e. preparates not subjected to any
      viral inactivation methods. The aim of the present study was to assess the
      prevalence of HCV, HBV and HIV infections among Polish haemophiliacs. MATERIALS
      AND METHODS: Severe haemophilia patients were divided into two age groups
      according to the type of replacement therapy used in the past: group 1--172
      patients born 1935-1990, group 2--41 patients born 1991-2002. The following viral
      markers were tested: anti-HCV, RNA HCV (if needed--virus genotype), HBsAg and
      anti-HIV. In 75 patients / group 1 and 41 / group 2, anti-HBc presence was
      determined. RESULTS: In group 1, 95% of patients were anti-HCV positive and in
      77.3% RNA HCV was detected. The most prevalent was lb genotype (58.6%) followed
      by 3a (27%). HBsAg was found in 8.7% cases of group 1. Anti-HCV antibodies were
      detected in 51 of 75 (68%) patients of this group. One patient was anti-HIV
      positive. In only one patient of group 2 (2.4%) viral markers were detected (anti
      HCV and RNA HCV). CONCLUSION: Nowadays, the risk of HCV, HBV and HIV infection in
      Polish severe haemophiliacs is very low.

PMID- 18807490
TI  - [Primary hepatotropic viral infections in Mongolia].
AB  - Mongolia is known for its high endemicity for viral hepatitis infections,
      accounted for 25% of infectious disease cases in 2000. Studies revealed these
      infections are prevalent among young adults in Mongolia. The infections are first
      and foremost nosocomial infections. The incidence of primary liver cancer, caused
      HBV, HDV and HCV chronic infections has increased in the last several years.
      Although viral hepatitis infections are recognized as a serious health problem in
      the country, not many epidemiological and clinical studies have been done. Few
      studies that were done were conducted among limited numbers of high risk
      subjects. These reports indicated that HBsAg prevalence was between 6.9% and
      28.7% and anti-HCV prevalence was between 10.7% and 48% in different population
      samples and in different years. More studies are needed to determine the real
      magnitude of hepatitis infections in the general population and to isolate and
      reduce the exposures specific to at risk population groups. National programs
      controlling hepatitis infections includes primary prevention strategies such as
      education, vaccination and infection control particularly in hospital settings,
      must be implemented to improve the awareness about hepatitis infection especially
      among youth, women and blood donors.

PMID- 18807491
TI  - [Prevalence of antibodies against hepatitis E virus among students from India
      living in Bialystok, Poland].
AB  - Many evidences suggest hepatitis E virus (HEV) infections may be more prevalent
      than previously described and viral hepatitis E cases can be observed in patients
      who have never visited endemic areas. The aim of this study was to assess the
      prevalence of serological markers of HEV infection among students from India
      living in Poland. METHODOLOGY: Presence of anti-HEV immunoglobulin M-class (anti
      HEV-IgM) and total anti-HEV antibodies (anti-HEV-total) was tested using enzyme
      immunoassays in sera of 45 India citizens studying in Poland. RESULTS:
      Serological markers of past or present HEV infection were detected in 12 (26.7%)
      subjects. Anti-HEV-total were found in 5 students (11.1%), anti-HEV-IgM alone
      were detected in 3 persons and in combination with total anti-HEV in further 4.
      CONCLUSIONS: There is a possible risk of person-to-person transmission of
      imported HEV from endemic areas, therefore HEV infection should be considered in
      all acute hepatitis patients regardless of travel history.

PMID- 18807492
TI  - [Microbiological evaluation of risk of legionellosis and practical methods
      applied for elimination of Legionella pneumophila from hospital water systems].
AB  - Microbiological evaluation of risk of legionellosis was based on the results of
      water samples collected from hospital water systems examinations. The percentage
      of positive water samples, number of detected Legionella spp. cfu/100ml,
      determined serogroup and subgroup of isolated strains as well as genetic
      virulence markers (rtxA, mompS) were analyzed by multivariable regression tests.
      The ability to adhere to cells A549 and proliferate in THP-1 cells were also
      examined. Strong correlation was found between the detected number of Legionella
      spp. cells (cfu/100ml) and percentage of positive samples, presence of gene
      depending ability bacteria to move, adhere to A549 cells and presence of mompS
      gene for special protein building capsule. From other side, correlation between
      identified cases or infections due to L. pneumophila and presence of gene: rtxA,
      mompS, and epitop MAb3/l was determined. In conclusion it was indicated that
      evaluation of risk of legionellosis should be based on ability the legionellae
      strains to prolify, and grow in water systems and also on virulence properties of
      isolated strains, especially those producing RTX toxin, flagella and presenting
      virulence epitop MAb3/l. Two examples of practical application methods for
      reduction of risk of nosocomial infection were described also. It was shown that
      cooperation of engineers and microbiologist is essential for effective
      elimination of Legionella from water systems and reduction of the risk of
      Legionella infection in hospital.

PMID- 18807493
TI  - [May ureaplasmas in genital tract of HPV-positive women influence abnormal
      cytology of cervix?].
AB  - The aim of the study was to estimate the incidence of Ureaplasma urealyticum
      (U.u.) and Ureaplasma parvum (Up.) in 168 women diagnosed with LSIL infected and
      not infected with HPV vs. 82 women with no cytological abnormalities in the
      cervix (control group). The material used in the study were cervical secretions
      samples. PCR was used to confirm the presence of HPV and to identify the species
      of ureaplasmas. U.p. was significantly more frequent in both groups of women. In
      the study group, ureaplasmas were more frequently isolated in the HPV infected
      (31%) vs. HPV negative (16%) women. No direct relationship was found between
      ureaplasmas and LSIL. Statistical analysis showed, that infection with HPV
      occurred more frequently in the presence of ureaplasmas (OR = 1.79; 95% PU 0.90
      3.53; p = 0.093). The above relationship was most evident for U.u. The risk for
      HPV infection in that case was 6.5 fold higher. Infections with ureaplasmas,
      especially U.u should be considered as a factor increasing the risk of HPV
      infection of the cervical epithelial cells.

PMID- 18807494
TI  - [Statistical analysis of influence of meteorological data on the incidence rate
      of tick-borne encephalitis in Bialystok].
AB  - The paper describes estimating the tick-born encephalitis incidence rate by
      meteorological data using linear regression method. The study shows 2 models of
      TBE incidence. First one describes general dependency between temperatures and
      TBE incidence (1972-2004). The second one (1994-2004) tries to find out more
      specific characteristics.

PMID- 18807495
TI  - [Classification bias in epidemiological studies].
AB  - The article describes problems caused by measurement bias of categorical
      variables in epidemiological studies. It analyses attenuation of measures of
      association, which can be related to misclassification in epidemiological
      studies. Problems with correction for confounders in the presence of
      misclassification of exposure are also described.

PMID- 18807496
TI  - [Evidence based medicine (EBM) in health care system and individual patients
      treatment. Part I. EBM in health care system].
AB  - The cooperation of activities of quality management in health care as HTA, QA,
      EBM has been considered. It was shown that EBM is independent information system
      for formulating guidelines and decision making placed between HTA and QA.
      Althought EBM is based on epidemiological knowledge and inspired epidemiological
      research is not by itself a part of epidemiology.

PMID- 18807497
TI  - [Diversity of proteasomes in mammals and its biological significance].

PMID- 18807498
TI  - [Functions of receptor-type protein tyrosine phosphatase in the formation of
      retinal projection].

PMID- 18807499
TI  - [Crystal structure of p40(phox) and regulation mechanism of superoxide
      generation].

PMID- 18807500
TI  - [Revival of natural antisense transcripts].

PMID- 18807501
TI  - [Structural changes of transthyretin and its cytotoxicity].

PMID- 18807502
TI  - [Applications of relaxation dispersion spectroscopy].

PMID- 18807503
TI  - [Regulation of inflammatory genes by the nuclear protein IkappaB-zeta].

PMID- 18807504
TI  - [Integral assessment of endogenous intoxication in patients with purulent
      mediastinitis].
AB  - The parameters of endogenous intoxication (EI) were studied in patients with
      purulent mediastinitis (PM). The integral index of E1--the coefficient C(EI) that
      included the relative indices (as to the normal values) of the total and
      effective concentrations of albumin, medium molecular-weight peptides, leukocytic
      intoxication index, and malonic dialdehyde, was developed. The values multiplied
      together are C(EI) and reflect the manifestation of EI. The level of EI in
      patients with PM was ascertained to be much increased on postoperative days 1 and
      3. Extracorporeal hemocorrection (plasmapheresis, prolonged venovenous
      hemofiltration) used in complex therapy diminishes the degree of EI by several
      times, on day 10 after surgery in particular. The use of C(EI) is shown to
      considerably increase the diagnostic sensitivity of the early stage of EI, to
      prescribe adequate detoxifying therapy in time, and to evaluate its efficiency.

PMID- 18807505
TI  - [Determination of serum antioxidative capacity in cancer patients].

PMID- 18807506
TI  - [Prooxidative characteristics of plasma from the psoriatic patients based on
      malonic dialdehyde level].
AB  - The values of malonic dialdehyde (MDA) were studied in 152 patients with
      different forms of psoriasis during the pathological process. The level of MDA
      was found to depend on the severity and extent of the process and on the presence
      of complications. Higher and persistent changes in MDA levels were observed in
      patients with complicated and disseminated forms of the disease. The authors show
      it possible to clinically use the determination of MDA levels to evaluate the
      prooxidative processes in psoriatic patients for diagnostic and prognostic
      purposes.

PMID- 18807507
TI  - [Lipid peroxidation in hypertensive disease concurrent with chronic obstructive
      pulmonary disease].
AB  - A hundred and thirty-four hypertensive patients were examined, 75 of them had
      concomitant first-degree chronic obstructive pulmonary disease (COPD). As
      compared with the control group, the patients were found to have elevated levels
      of primary, secondary, and intermediate products of serum lipid peroxidation and
      lower activities of catalase of red blood cells and their peroxide resistance.
      All changes were most pronounced in concomitant COPD.

PMID- 18807508
TI  - [Characteristics of endogenous intoxication in children with Helicobacter pylori
      associated gastroduodenal diseases].
AB  - Endogenous intoxication indices, such as the levels of medium-weight molecules
      and oligopeptides, albumin binding ability, and the blood activity of NADH
      alcohol dehydrogenase, were studied in 326 children with chronic gastroduodenitis
      and duodenal ulcerative disease, including 252 and 74 children with and without
      Helicobacter pylori infection, respectively. High endogenous intoxication was
      detected in the presence of Helicobacter pylori. The paper shows it possible to
      use the level of medium-weight molecules and oligopeptides, toxicity index, the
      blood activity of NADH-alcohol dehydrogenase as biochemical markers of the
      negative impact of Helicobacter pylori.

PMID- 18807509
TI  - [Apoptosis and micro- and macroelement composition of lymphocytes in patients
      with pulmonary tuberculosis].
AB  - The paper describes the results of comparatively analyzing the parameters of
      apoptosis, micro- and macroelement spectrum of peripheral blood lymphocytes in
      healthy donors and in patients with chronic obstructive pulmonary disease (COPD)
      and pulmonary tuberculosis. In drug-responsive and drug-resistant pulmonary
      tuberculosis, unidirectional pretreatment changes were generally recorded in the
      activity of apoptosis and the spectrum of chemical elements of peripheral blood
      lymphocytes, which were most pronounced after completion of a phase of intensive
      antituberculosis chemotherapy. After termination of a complete course of the
      therapy, apoptotic activity lowered with the cationic composition of cells being
      normalized. The parameters differentiating pulmonary tuberculosis from COPD were
      ascertained, these included increases in the count of apoptotic cells and the
      cell concentrations of Ca2+, Zn2+, and Mg2+.

PMID- 18807510
TI  - [Diagnostic value of antibodies to modified citrullinized vimentin in early
      rheumatoid arthritis].
AB  - A hundred and two patients (18 males, 84 females; mean age, 50.3 +/- 12.3 years)
      diagnosed as having early rheumatoid arthritis (RA) were examined. A control
      group consisted of 189 patients with various rheumatic diseases and 30 healthy
      donors. The serum concentrations of antibodies to modified citrullinized vimentin
      (MCVA) and to cyclic citrullinized peptide2 (CCTP2A) were measured by enzyme
      immunoassay (EIA); rheumatoid factor (RF) IgM was determined by nephelometric
      immunoassay. In early RA, the level of MCVA (median, 49.6 U/ml; interquartile
      range, 0.9-249.3) was significantly higher than in the control group 1.65 U/ml;
      0.3-19.7). There was a direct significant correlation between the levels of MCVA
      and CCTP2A (p = 0.9), as well as RF IgM (p = 0.6). The diagnostic efficiency of
      MCVA (area under the curve, 0.705; 95% confidence interval, 0.607-0.803) was
      higher than that of CCTP, (0.590; 0.467-0.714), but lower than that of RF IgM
      (0.813; 0.736-0.889). MCVA was comparable with CCTP, and RF IgM in sensitivity;
      however, it ranked below them in specificity (71%). Choice of the optimum upper
      normal range (30 U/ml) permits up to an 88% increase in MCVA specificity and the
      concurrent consideration of results of testing MCVA, CCTP2A, and RF IgM is
      attended by up to a 78% increase in sensitivity. EIA of MCVA is a sensitive and
      specific serological test for the diagnosis of early RA.

PMID- 18807511
TI  - [Influence of pH values on the agglutinating capacity of anti-A-monoclonal
      antibodies and their inhibition of A-glucoconjugates of the lipid and protein
      nature with various isoelectric properties].
AB  - The effect caused by medium acidification up to pH 6.5 on the agglutinating
      ability of 7 anti-A MAbs (2-8, 2-17, 2-19, 2-22, 2-23, 2-28 from Workshop IV and
      BRIC-145) and their inhibition by glycoconjugates obtained from the membranes of
      A1 erythrocytes by enzymatic treatment and the chloroform-methanol method,
      followed by ion-exchange gel chromatography, was evaluated. Medium acidification
      most significantly reduced the agglutination of A1 erythrocytes in IgM MAbs 2-17
      , 2-19, 2-22, and 2-28 and had a weaker manifestation in more alkaline IgM MAbs 2
      8, 2-23, and BRIC-145. The inhibition of the lipid isotypes A(1p-00), A(1p-0),
      and A(1p-3) (with the isoionic pH points of 8.1, 8.0, and 6.55) and the protein
      ones A(pr-1), and A(pr-3) (with the isoionic pH points of 7.15 and 6.45) was
      assessed in scores. Acidification up to a pH value of 6.5 in MAbs 2-28 and 2-17
      caused a considerable reduction in inhibition with acid A(1p-3) and A(pr-3) with
      slightly increased inhibition with alkaline A(1p-00); MAbs 2-22 and 2-19
      insignificantly and selectively altered the inhibitory capacity by more alkaline
      types of glycoconjugates; MAb 2-8 hardly changed inhibition. All the above
      illustrates a significant part played in the study effect by both the charge of
      glycotopes and antibodies and specificity--the selective avidity of MAbs to
      certain isotypes of A glycotopes.

PMID- 18807512
TI  - [Stem cells and their structure-function relationships with the connective
      tissue].

PMID- 18807513
TI  - [Current methods for detection of anti-erythrocytic antibodies in blood donors].
AB  - Erythrocytic antibody screening in donors aids in reducing the risk of
      posttransfusion reactions and complications; donors with serum immune antibodies
      are taken from donation of plasma and transferred to that of erythrocyte
      containing media. The application of highly sensitive tests for antibody
      screening permits detection of antibodies of wide range and various specificity
      and immunogenicity. The antibody identification technique makes it possible to
      establish a priority scale of transfusionally dangerous erythrocytic antigens.

PMID- 18807514
TI  - [Effect of phenylcarboxylic acids on phagocytic activity of neutrophils].
AB  - Neutrophylic phagocytosis is affected by a lot of factors, including
      phenylcarboxylic acids secreted by bacteria into blood to protect from
      phagocytosis. The paper describes the most likely mechanism of inhibiting action
      of these acids, which is associated with the formation of strong pi-complexes
      between the pi-bonds of the molecular benzene ring of the acids and pi-bonds of
      unsaturated fatty acid molecules of the neutrophilic membrane. This fact was used
      to calculate the minimum inhibitory concentration of an acid and to show that
      there may be saturation in inhibition from the concentration. The experiment
      wherein the acids were added to blood at varying concentrations has confirmed the
      inhibitory effect of the acids, as well as saturation. Data processing indicates
      the unifactor inhibition of phagocytosis and confirms the postulated exponential
      inhibition at acid concentrations of to about 10(-7) mole/l. There is saturation
      with further acid concentration increases and there is a further reduced
      phagocytosis due to the influence of pH at a concentration of more than 10(-5)
      mole/l.

PMID- 18807515
TI  - [Rapid cytological method in the diagnosis of ovarian cancer].

PMID- 18807516
TI  - [Immunomorphological characteristics of pulmonary langerhans cell histiocytosis].
AB  - Lung tissue specimens, obtained during lung biopsy or resection, were
      morphologically and immunohistochemically studied in 27 patients with Langerhans
      cell (LC) histiocytosis (LCH). The latter was diagnosed on the basis of the
      expression of CD1a and S-100. Without immunophenotyping, its diagnosis was
      difficult due to impaired tissue architectonics (sclerosis, bullous
      transformation) and artifacts that were inevitably present during lung biopsy.
      LCs in the infiltrates were shown to be capable for apoptosis. Induction of LC
      apoptosis may be regarded as a therapeutic strategy.

PMID- 18807517
TI  - [Correlation of p16/INK4a gene damages and protein expression in the tumor tissue
      of sporadic breast cancer].
AB  - A tumor emerges due to the structural and functional abnormalities occurring in
      the genes, which causes a change in the spectrum of protein molecules. Strong
      correlations between the gene damages and following changes in the protein
      spectrum make it possible to study different stages of carcinogenesis and to
      create a more complete system of molecular markers for the diagnosis of different
      types of tumors, which comprises protein markers and DNA markers. The present
      investigation has studied a correlation between the inactivation mechanisms
      (structural and functional) of the suppressor gene p16/INK4a, which occur at the
      level of DNA, and the results of its protein expression examined by
      immunohistochemical methods in the tumor specimens from patients with breast
      cancer. The investigation could indicate that p16/INK4a gene damage frequently
      occurred in the tumors of the above type. In the majority of study cases,
      molecular damages revealed in the gene diminish on its protein expression;
      however, there are still cases that defy generally accepted explanations.

PMID- 18807518
TI  - [Ultrastructural and immunohistochemical features of thyroid cancer].
AB  - The morphofunctional diagnosis of different forms of thyroid cancer should be
      made by immunohistochemical and electron microscopic studies.

PMID- 18807519
TI  - [Immunohistochemical study of mucins in chronic pancreatitis and ductal
      adenocarcinoma of the pancreas].
AB  - Based on the results of an immunohistological study of MUC1, MUC2, MUC4, MUC5AC,
      and MUC6 in pancreatic tissue from 50 patients with chronic pancreatitis (CP) and
      50 patients with ductal adenocarcinoma (DAC), the authors showed altered mucin
      immunological responsiveness in severe forms of CP, in the foci of PanIN and DAC.
      They also revealed that determination of mucin expression may be used in the
      differential diagnosis of pancreatic cancer.

PMID- 18807520
TI  - [Prevalence of different histological types of brain tumors in the volgograd
      region according to the data of intraoperative biopsies over the period of 2001
      to 2006].
AB  - The prevalence of different histological types of brain tumors was analyzed in
      the Volgograd Region from the data of intraoperative biopsies over the period of
      2001 to 2006. Gliomas were a dominant group (51.9%) at all study time intervals.
      Among them, there was a preponderance of glioblastomas (24.7%), anaplastic
      astrocytomas (21.1%), protoplasmatic astrocytomas (15.4%). The fact that
      heterogenic tumor tissue in a great deal of the study cases of malignant gliomas
      makes pathohistologists' opinion differ and suggests that there is a need for an
      in-depth study of intraoperative biopsy specimens, by using the existing antibody
      panels and developing new ones for immunohistochemical studies.

PMID- 18807521
TI  - [Intraneural perineurioma: clinical and morphological characteristics and a
      molecular genetic study of the neurofibromatosis type 2 gene].
AB  - The authors describe 4 cases of clinically, morphologically, and
      immunohistochemically typical intraneural perineuriomas that occurred in women
      aged 17 to 24 years. The tumors involved median, radial, ulnar, and palmar nerves
      and were 3, 2.5, 1.5, and 1.2 cm in the largest diameter. None patients had signs
      ofneurofibromatosis type 2 (NF2). One case was studied for mutation of the NF2
      gene and heterozygous splice-site mutation at the acceptor splice site between
      exons 12 and 13 (agGG --> aaGG) was revealed. Two patients were followed up: they
      were disease-free for 10 and 15 years.

PMID- 18807522
TI  - [Investigation of the morphometric parameters of the visual cortical region
      (Field 17) in perinatal brain damage].
AB  - Autopsy brain specimens from babies who had experienced perinatal central nervous
      system damage and those who had shown no symptoms of brain lesion (a control
      group) were used to study the structural characteristics of Field 17 of the
      visual cortical region, by using computed morphometry. As compared with the
      control group, the children who had suffered from perinatal pathology showed no
      relationship between the increased width of a cortical plate diameter and the
      baby's age and Layers I and V had a significantly less width. In most cases
      Layers III, V and Layer VI + VII contained smaller neurons and the density of
      their arrangement was much less than in the brain of the control babies. It was
      concluded that the detected disorders suggest growth retardation and nonspecific
      structural and functional changes in the visual cortex in perinatal brain damage.

PMID- 18807523
TI  - [Possibilities of cytological diagnosis of central nervous system tumors].
AB  - The cytological and pathohistological pictures of 384 glial, meningeal,
      embryonic, neuronal, metastatic tumors and tumors growing into the cranial cavity
      and spinal canal (the impression smears of removed tumor fragments and the
      aspirates on fine needle puncture) were studied in parallel. The common
      supporting cellular and structural signs required for the diagnosis of the major
      groups of central nervous system (CNS) tumors, for the verification of some
      histological types of a neoplasm, and for the estimation of the stage of their
      malignancy were revealed. An algorithm of cytological diagnosis of some CNS
      tumors and an adapted working classification are proposed.

PMID- 18807524
TI  - [Endometrial morphological and immunohistochemical features in females with
      primary and secondary infertility].
AB  - Endometrial scrapes and biopsy specimens from 47 females with primary and
      secondary infertility were studied by histological and immnohistological
      (estrogen and progesterone receptors, Ki67) methods. Endometrial abnormalities,
      such as luteal phase defect, hyperplasia, endometrial polyps, and chronic
      endometritis, were detected in all the patients. There were considerable changes
      in the expression of estrogen and progesterone receptors and impaired endometrial
      proliferative processes. There was no clear correlation of immunohistochemical
      parameters with blood hormone levels in both primary and secondary infertility.
      The findings may be of significance in choosing the schemes of assisted
      procreation technologies.

PMID- 18807525
TI  - [The pathogenesis of uterine hemorrhages in the so-called placental polyps].
AB  - On the basis of histological and immunohistochemical studies of 50 uterine
      scrapes after abortions and labor due to late bleedings, the authors identified
      three major types of the so-called placental polyps: (a) preserved villi (56%);
      (b) clusters of destructive villi (38%); (c) isolated viable cotyledons (6%). Two
      pathogenetic mechanisms of uterine hemorrhages have been substantiated: firstly,
      preservation of the brush border of a syncytiotrophoblast (including the presence
      of placental phosphatase) maintains the anticoagulative properties of villi; this
      appears in cases of postabortion hemorrhages and at the most in preserved
      cotyledons. Secondly, the thromboplastic properties of the preserved villi play a
      leading role in the pathogenesis of uterine hemorrhage in the scrapes where
      necrotic villi with epithelial remains are prevalent, i.e. the situation is
      similar to the hypocoagulative phase of isolated chronic disseminated
      intravascular coagulation.

PMID- 18807526
TI  - [Neonatal bronchopulmonary dysplasia: morphogenesis, morphological diagnosis].
AB  - Four groups of changes (premorbid, paradysplastic, nonspecific, and
      pathognomonic) have been detected in the lung of 64 dead children w ith neonatal
      bronchopulmonary dysplasia (NBPD) on artificial ventilation (AV) for an average
      of 20 +/- 0.1 days. In the latter group, the authors have identified the key
      structures that reflect the pathogenetic action of aggressive factors of AV and
      that are diagnostic markers of the 4 detected stages of NBPD morphogenesis:
      bronchiolectasis and stellar atelectasis (Stage 1); rosette-like bronchioli
      (Stage 2); mosaic pneumosclerosis and fibroatelectases (stellate, moire, and
      fibromuscular) (Stage 3); and honeycomb lung (Stage 4).

PMID- 18807527
TI  - [Pathomorphological changes in the lung in acute posthemorrhagic anemia].
AB  - Lung tissue was histologically studied in 30 cadavers of those who had died from
      acute hemorrhage. When death occurred, several minutes after blood were marked by
      emphysema without alveolar edema and lymph-macrophageal infiltration of
      interalveolar septa whereas 1.5-2 hours after blood loss, emphysematous changes
      in lung tissues were accompanied with significant lymph-macrophageal infiltration
      of interalveolar septa and intraalveolar edema and with the signs of micro
      disseminated intravascular coagulation in the lung. Desquamation and necrotic
      changes of alveocytes were observed. At death, 24 hours or more following blood
      loss, there was, along with alveocytic necrotic changes in lung tissue, type 2
      pneumocytic proliferation, as well as alveolar hemorrhages, vascular thrombosis
      in the microcirculatory bed, fibrin lumps and threads in the alveolar lumen.

PMID- 18807528
TI  - [Papillary glioneuronal tumor is a new nosological entity in the WHO
      classification of central nervous system tumors (2007)].
AB  - The paper describes a case of cystic papillary glioneuronal tumor of the temporal
      lobe in an 18-year-old girl. It is shown that in addition to the characteristic
      histological pattern, the diagnosis of this rare neoplasm recently included into
      the WHO classification text s should be verified by the immunohistological
      evidence suggesting the coexpression of glial and neuronal markers.

PMID- 18807529
TI  - [The informative value of pericardial fluid electrolytes and glucose in acute
      forms of coronary heart disease].
AB  - The informative value of the levels of calcium, potassium, sodium, magnesium, and
      glucose was estimated in individuals who had suddenly died from acute coronary
      insufficiency or acute myocardial infarction in the prenecrotic phase. The
      informational variations in the concentrations of electrolytes and glucose were
      found to reflect the differences available in the pathogenesis of an ischemic
      process in acute coronary insufficiency and acute myocardial infarction in the
      prenecrotic phase.

PMID- 18807530
TI  - [Skvortsov's contribution to the rheumatism teaching].

PMID- 18807531
TI  - [Glycodelin as a potential marker of female genital system tumors (a review of
      literature)].
AB  - The authors present the currently available data on the expression of glycodelin,
      a unique secretory protein of the human reproductive system, which has gender
      dependent glycosylation, immunosuppressive and morphogenetic activities, in
      gynecological cancers. They also discuss the theoretical and practical aspects of
      studying glycodelin as an effector and a marker molecule of oncogenesis.

PMID- 18807532
TI  - [To categories of discrepancy between clinical and postmortem diagnoses].
AB  - The paper continues the discussion started by I. A. Kazantseva and deals with
      that whether it is expedient to identify 3 categories of discrepancy between
      clinical and postmortem diagnoses (Ark. Pat., 2007, No. 6, p. 56-57). The author
      considers it untimely to deny the mentioned categories that are generally
      accepted and popular. His viewpoint is supported by the leading pathologists of
      Saint Petersburg. The paper also contains concise data on the frequency of
      hospital autopsies in Europe and the U.S.A. and knowledge on L. Goldman's
      classification considering the discrepancies in ante- and postmortem diagnosis.

PMID- 18807533
TI  - [A pathologist's radiological culture].
AB  - The authors analyze 8 papers on human radiation pathology, published in the
      journal "Arkhiv Patologii", which assess the quality of radiological information
      given in them. It turns out that pathologists have accumulated important facts on
      some types of pathology (thyroid cancer, diseases of different organs), but their
      dependence on the action of radiation requires more valid evidence. The absence
      of radiation doses in most papers reduces the validity of the conclusions of the
      articles. All possible internal and external causes of the found changes, and not
      just ionizing radiations should be considered while interpreting results.

PMID- 18807534
TI  - [How to reduce mortality from cardiovascular diseases].

PMID- 18807536
TI  - [A rapid all-round progress and unwanted losses in diagnosis].

PMID- 18807535
TI  - [Hypertrophic cardiomyopathy: course characteristics in long-term follow-up].
AB  - AIM: To detect relations between intracardiac hemodynamics and clinicoanamnestic
      features of patients with hypertrophic cardiomyopathy (HCMP). MATERIAL AND
      METHODS: We observed 84 patients with different clinical variants of a HCMP
      course. Of them, 15 patients were treated surgically. The patients were followed
      up from 3 to 24 years (mean 8.4 +/- 1.1 years). All the patients have undergone
      standard ECG, transthoracic echocardiography with doppler echocardiography, 24-h
      ECG monitoring, part of them--stress echocardiography (exercise and/or
      dobutamine), MRT of the heart, coronaroangiography and probing of the heart.
      RESULTS: The analysis of cardiac remodeling parameters in HCMP patients showed
      significance of diastolic disorders in development of basic clinical symptoms of
      the disease. A rise of atrial-ventricular index (AVI) reflects severity of a HCMP
      course. Patients with the most severe course of the disease had AVI equal or
      higher than 1.1. In obstructive and non-obstructive variants of HCMP time of the
      first symptoms onset did not differ significantly. In the disease onset the
      patients had asthenic syndrome, cardialgia, dyspnea. The disease ends with heart
      failure. CONCLUSION: Long-term follow-up of HCMP patients and comparison of
      clinico-morphological parameters revealed the role of diastolic dysfunction in
      formation of clinical symptoms.

PMID- 18807537
TI  - [Cardiorenal syndrome in ischemic renal disease (atherosclerotic renovascular
      hypertension)].
AB  - AIM: To characterize cardiorenal syndrome in ischemic renal disease (IRD).
      MATERIAL AND METHODS: In examination of 105 IRD patients (63 males and 42
      females, mean age 63.8 +/- 5.1 years) we estimated body mass index (BMI), indices
      of peripheral blood and urine, blood biochemistry, glomerular filtration rate
      (GFR). Plasmic homocystein concentration was measured in 30 patients. We also
      studied incidence of some cardiovascular risk factors, clinical variants of
      atherosclerosis and their correlation with GFR. RESULTS: IRD patients most
      frequently had hypertriglyceridemia (67.6%), hypercholesterinemia (53.3%),
      smoking (47.1%), obesity (41.9%), metabolic syndrome (38.1%), type 2 diabetes
      mellitus, arterial hypertension of the third degree (70.6%), isolated systolic
      arterial hypertension (46.7%). GFR was significantly lower in smokers (p <
      0.001), arterial hypertension of the third degree (p < 0.05), isolated systolic
      arterial hypertension (p < 0.001) and type 2 diabetes mellitus (p < 0.05). In GFR
      < 40 ml/min homocysteinemia increased significantly (p < 0.01). Coronary artery
      disease in IRD occurred in 52.4%, cerebrovascular diseases (brain stroke,
      transitory ischemic attacks)--in 29.5%, intermittent claudication--in 19.0%,
      aneurism of the abdominal aorta--in 7.6%, documented atherosclerotic affection of
      the upper limb arteries--in 2.8%. Patients with intermittent claudication were
      characterized by significantly less GFR compared to that in patients without
      clinical symptoms of affected arteries of the lower limbs (38.6 +/- 8.2 and 44.6
      +/- 7.3 ml/min, respectively; p < 0.01). CONCLUSION: Basic symptoms of
      cardiorenal syndrome in IRD are high rate of cardiovascular risk factors, some of
      them provoke aggravation of glomerular endotheliocyte dysfunction and
      deterioration of intrarenal hemodynamics leading to GFR reduction underlying
      appearance of new endothelium-tropic risk factors (hyperhomocysteinemia), and
      progression of atherosclerotic process with formation of its special clinical
      forms (intermittent claudication).

PMID- 18807539
TI  - [Infectious diseases. New problems].

PMID- 18807538
TI  - [Abdominal pain in therapeutic practice].

PMID- 18807540
TI  - [Chronic obstructive pulmonary disease and associated illnesses].

PMID- 18807541
TI  - [Affection of cardiovascular system in antiphospholipid syndrome with non
      bacterial thrombotic endocarditis].
AB  - AIM: To study characteristics of cardiovascular affection in antiphospholipid
      syndrome (APS) with nonbacterial thrombotic endocarditis (NBTE). MATERIAL AND
      METHODS: The trial included 28 patients with APS and NBTE (26 females, mean age
      44 <+/- 13 years). Primary APS was diagnosed in 21 patients, secondary APS
      associated with systemic lupus erythematosus--in 7 patients. Transthoracic
      echocardiography was performed in all the patients, transesophageal
      echocardiography--in 86% of them. Statistic processing was made with logistic
      regression analysis. RESULTS: All the patients had structural valvular changes:
      leaflet thickening, sclerosis, vegetations, focuses of calcinosis and valvular
      dysfunction. Vegetations located on mitral and aortic valves in 64% and occurred
      on damaged heart valves in 36% patients. An important problem in APS with NBTE
      was systemic embolism (54%), especially with involvement of central nervous
      system. Logistic regression revealed association of NBTE with structural changes
      of aortic and mitral valves, myocardial focal fibrosis and valvular
      insufficiency. CONCLUSION: APS with NBTE is characterized by absolute
      predominance of valvular heart lesion with vegetations location on the left heart
      valves and high risk of embolic complications.

PMID- 18807542
TI  - [Acute renal failure caused by cholesterol embolism of the intrarenal arteries
      after coronaroangiography: success of glucocorticosteroid treatment].

PMID- 18807543
TI  - [Administration of monoclonal antibodies to B-lymphocytes (rituximab) in
      rheumatoid arthritis in Russia].
AB  - AIM: To assess efficacy and tolerance to anti-B-cell drug rituximab in therapy of
      rheumatoid arthritis (RA) by the data of RF register of this drug. MATERIAL AND
      METHODS: Rituximab was studied in 42 patients with high RA activity. 37 patients
      received rituximab according to a conventional scheme: 2 intravenous 1000 mg
      infusions with a 2-week interval. The rest patients received 2 intravenous 500 mg
      infusions. The response was evaluated by DAS28 index. RESULTS: Rituximab
      administration resulted in almost complete elimination of B-cells from peripheral
      blood. This produced a significant positive effect manifesting with reduction in
      the number of inflamed and painful joints. This trend was evident to observation
      week 8 reaching maximum to week 24. Clinical response correlated with decline of
      inflammation as shown by ESR and CRP. According to DAS28 index, good and
      satisfactory results were registered in 8 weeks in 62% patients, in 16 weeks--in
      86%, in 24 weeks--in 100%. Rituximab tolerance was good. CONCLUSION: Effective
      treatment with rituximab for rheumatoid arthritis opened a new perspective in
      antirheumatic biological therapy and demonstrated an important role of B-cells in
      the disease development. This drug is recommended for wide use in the treatment
      of severe rheumatoid arthritis resistant to prior therapy including TNF-alpha
      blockers.

PMID- 18807544
TI  - [Simvastatin effects on the disease activity and cholesterol content in blood
      serum lipoprotein subfractions in patients with rheumatoid arthritis].
AB  - AIM: To study activity of rheumatoid arthritis (RA) and cholesterol content in
      subfractions of blood serum lipoproteins in the course of simvastatin treatment.
      MATERIAL AND METHODS: The pilot study enrolled 16 patients with active rheumatoid
      arthritis (RA) meeting ACR criteria. Any standard anti-RA medication in stable
      doses was supplemented with simvastatin in a dose 40 mg/day for 12 weeks. The
      response was assessed by contents of cholesterol in serum lipoprotein
      subfractions and DAS28 index. RESULTS: At the end of the treatment course there
      was a significant elevation of HDLP2 and HDLP3 cholesterol and reduction in the
      levels of LDLP1-3 and LDLP cholesterol. DAS28 decreased by 0.89 points to the end
      of the treatment. CONCLUSION: Administration of simvastatin in patients with
      active RA on standard disease-modulating drugs has an antiatherogenic action and
      attenuates the disease activity. These pilot data should be confirmed by further
      large-scale controlled trials.

PMID- 18807545
TI  - [Prevalence of gastroesophageal reflux disease in Moscow: results of a population
      study].
AB  - AIM: To study prevalence of the principal symptoms of gastroesophageal reflux
      disease (GERD) in Moscow. MATERIAL AND METHODS: A total of 1065 respondents aged
      15-85 years (a random representative sample of population of one of the typical
      Moscow districts) participated in a questionnaire survey using the international
      questionnaire for detection of GERD incidence. RESULTS: Epigastric burning (EB)
      occurs in 39.6% examinees. GERD prevalence is 14.2%. Subjects with EB have the
      following symptoms of GERD: regurgitation (66.3%), epigastric pain (discomfort)
      (53.0%), nausea (43.6%), vomiting (23.2%), dysphagia (20.6%), chest pain (18.0%),
      odinophagia (5.5%), singultus (4.6%). There is a direct correlation between
      incidence rate of EB, height, body mass index, number of alcohol excesses and
      smoked cigarettes. CONCLUSION: EB occurs in both young and aged men and women
      with similar frequency. Significant differences were detected only in the age
      group 45-59 years in which EB is more frequent in women. All the symptoms
      excluding cough and singultus were seen in women significantly more frequently.
      With age, these differences disappeared but noncardial pain in the chest that was
      less frequent in the elderly. Muscovites with GERD symptoms are older (61.26 +/-
      13.47 years) than those without such symptoms (58.44 +/- 16.28, p < 0.0001).

PMID- 18807546
TI  - ["Functionality" of antibodies: clinical implications].

PMID- 18807547
TI  - [Outpatient treatment. Stages of development. Perspectives].

PMID- 18807548
TI  - [Therapy as a base of national health promotion. Issues of medical ethics].

PMID- 18807549
TI  - [Is it possible to modify the course of chronic obstructive pulmonary disease
      with modern medication?].

PMID- 18807550
TI  - [Beta-adreno-blockers use in combination of cardiovascular and pulmonary
      diseases].

PMID- 18807551
TI  - [Pneumonia as a general medical problem].

PMID- 18807552
TI  - [Results of national congresses of therapists in the Russian Federation].

PMID- 18807553
TI  - Has implant dentistry become a boutique practice?

PMID- 18807554
TI  - Editorial opinion versus real data and knowledge of the literature.

PMID- 18807555
TI  - Strength of CAD/CAM-generated esthetic ceramic molar implant crowns.
AB  - PURPOSE: One-visit in-office CAD/CAM fabrication of esthetic ceramic crowns as a
      superstructure for posterior implants is quite new. The aim of the study was to
      evaluate the strength of esthetic ceramic CAD/CAM crowns with varied occlusal
      thickness and seated with adhesive and nonadhesive cements on titanium and
      zirconia abutments. MATERIALS AND METHODS: Esthetic ceramic CAD/CAM-generated
      molar crowns (n = 15 per group) with occlusal thicknesses of 0.5 mm and 1.5 mm
      were seated on titanium (1) and zirconia (2) abutments: noncemented (a) and with
      nonadhesive cement (b) or 2 adhesive resin-based cements (c) and (d). In
      addition, 15 molar crowns with 5.5-mm occlusal thickness were seated on short
      zirconia abutments (3) using cements (c) and (d). All crowns had the identical
      occlusal morphology and were loaded with a crosshead speed of 0.5 mm/min until
      fracture. Load data were analyzed using 2-way ANOVA, the Scheffe test, and
      Weibull probability of failure analysis. RESULTS: Fracture loads of 1.5-mm
      occlusal thickness crowns (a, b, c, d) were higher (P < .001) than those of 0.5
      mm crowns (except for group ld). Occlusal 5.5-mm crowns on short zirconia
      abutments had similar (2c) or less (2d) strength than the respective 1.5-mm
      crowns. Nonadhesive crowns (1b, 2b) were weaker (P < .001) than adhesive crowns
      (1c, 1d, 2c, 2d). Fracture loads of 0.5- and 1.5-mm crowns were significantly
      higher on titanium than on zirconia abutments with both cements. Adhesive cement
      d generally showed higher fracture loads than c on both titanium and zirconia.
      CONCLUSION: Esthetic ceramic CAD/CAM molar implant crowns gained high strength
      with adhesive cements on both titanium and zirconia implant abutments compared to
      nonadhesive cementation.

PMID- 18807556
TI  - A comparison of profilometer and AutoCAD software techniques in evaluation of
      implant angulation in vitro.
AB  - PURPOSE: The aim of this study was to compare 2 different methods of assessment
      of implants at different inclinations (90 degrees and 65 degrees)--with a
      profilometer and AutoCAD software. MATERIALS AND METHODS: Impressions (n = 5) of
      a metal matrix containing 2 implants, 1 at 90 degrees to the surface and 1 at 65
      degrees to the surface, were obtained with square impression copings joined
      together with dental floss splinting covered with autopolymerizing acrylic resin,
      an open custom tray, and vinyl polysiloxane impression material. Measurement of
      the angles (in degrees) of the implant analogs were assessed by the same blinded
      operator with a profilometer and through analysis of digitized images by AutoCAD
      software. For each implant analog, 3 readings were performed with each method.
      The results were subjected to a nonparametric Kruskal-Wallis test, with P < or =
      .05 considered significant. RESULTS: For implants perpendicular to the horizontal
      surface of the specimen (90 degrees), there were no significant differences
      between the mean measurements obtained with the profilometer (90.04 degrees) and
      AutoCAD (89.95 degrees; P = .9142). In the analyses of the angled implants at 65
      degrees in relation to the horizontal surface of the specimen, significant
      differences were observed (P = .0472) between the mean readings with the
      profilometer (65.73 degrees) and AutoCAD (66.25 degrees). CONCLUSIONS: The
      degrees of accuracy of implant angulation recording vary among the techniques
      available and may vary depending on the angle of the implant. Further
      investigation is needed to determine the best test conditions and the best
      measuring technique for determination of the angle of the implant in vitro.

PMID- 18807557
TI  - The influence of abutment angulation on micromotion level for immediately loaded
      dental implants: a 3-D finite element analysis.
AB  - PURPOSE: To investigate the micromotion between the implant and surrounding bone
      caused by the implementation of an angled abutment for an immediately loaded
      single dental implant located in the anterior maxilla. MATERIALS AND METHODS: A
      simplified half premaxillary bone model was fabricated. The dimension of the
      alveolar ridge was adopted from a dry human skull. Based on Branemark protocol
      for Mk IV implants in type-3 bone, an immediate loading model was developed by
      press-fitting a 4-mm-diameter cylinder implant into a 3.15-mm osteotomy site in a
      numeric model. Material properties were assigned to the simulated model, and the
      model was meshed. A bite force of 89 N was applied to the tops of the 0-degree,
      15-degree, and 25-degree angled abutments at a 120-degree angle to the abutment
      long axis. The micromotion between the bone-implant interfaces was calculated
      using ANSYS 9.0 software featuring a nonlinear contact algorithm. RESULTS: The
      micromotion values for 15-degree and 25-degree angled abutments were 119% and
      134%, respectively, compared to the corresponding values for straight abutments.
      Compared to straight abutments, the 25-degree abutments resulted in increased
      maximum von Mises stresses to a level of 18%. Most of the stresses were
      concentrated within the cortical bone around the neck of the implants.
      CONCLUSION: Within the limits of the present finite element analysis study,
      abutment angulation up to 25 degrees can increase the stress in the peri-implant
      bone by 18% and the micromotion level by 30%.

PMID- 18807558
TI  - Surface characteristics of electrochemically oxidized implants and acid-etched
      implants: surface chemistry, morphology, pore configurations, oxide thickness,
      crystal structure, and roughness.
AB  - PURPOSE: This study was undertaken to investigate surface properties of surface
      modified titanium implants in terms of surface chemistry, morphology, pore
      characteristics, oxide thickness, crystal structure, and roughness. MATERIALS AND
      METHODS: An oxidized, custom-made Mg implant, an oxidized commercially available
      implant (TiUnite), and a dual acid-etched surface (Osseotite) were investigated.
      Surface characteristics were evaluated with various surface analytic techniques.
      RESULTS: Surface chemistry showed similar fingerprints of titanium oxide and
      carbon contaminant in common for all implants but also revealed essential
      differences of the elements such as about 9 at% Mg for the Mg implant, about 11
      at% P for the TiUnite implant and about 12 at% Na for the Osseotite implant.
      Surface morphology of the Mg and TiUnite implants demonstrated a duplex oxide
      structure, ie, an inner barrier layer without pores and an outer porous layer
      with numerous pores, whereas the Osseotite implant revealed a
      crystallographically etched appearance with pits. The diameter and depth of
      pores/pits was < or = 2 microm and < or = 1.5 microm in the Mg implant, < or = 4
      microm and < or = 10 microm in the TiUnite implant, and < or = 2 microm and < or
      = 1 microm in the Osseotite implant, respectively. Oxide layer revealed
      homogeneous thickness, about 3.4 microm of all threads in the Mg implants. On the
      contrary, TiUnite showed heterogeneous oxide thickness, about 1 to 11 microm,
      which gradually increased with thread numbers. Crystal structure showed a mixture
      of anatase and rutile phase for the Mg implants. With respect to roughness, Sa
      showed 0.69 microm in the Mg implant, 1.35 microm in the TiUnite implant, and
      0.72 microm in the Osseotite implant. CONCLUSIONS: Well-defined surface
      characterization may provide a scientific basis for a better understanding of the
      effects of the implant surface on the biological response. The surface-engineered
      implants resulted in various surface characteristics, as a result of different
      manufacturing techniques.

PMID- 18807559
TI  - The effect of chemical and nanotopographical modifications on the early stages of
      osseointegration.
AB  - PURPOSE: To investigate the effect of chemically modified implants with similar
      microtopographies but different nanotopographies on early stages of
      osseointegration. MATERIALS AND METHODS: Forty screw-shaped implants were placed
      in 10 New Zealand white rabbits. The implant surface modifications investigated
      in the present study were (1) blasting with TiO2 and further (2) fluoride
      treatment or (3) modification with nano-hydroxyapatite. Surface evaluation
      included topographical analyses with interferometry, morphologic analyses with
      scanning electron microscopy, and chemical analyses with x-ray photoelectron
      spectroscopy. Bone response was investigated with the removal torque test, and
      histologic analyses were carried out after a healing period of 4 weeks. RESULTS:
      Surface roughness parameters showed a slight decrease of the average height
      deviation for the fluoride-treated compared to the blasted (control) and nano
      hydroxyapatite implants. Scanning electron microscopic images at high
      magnification indicated the presence of nanostructures on the chemically modified
      implants. Chemical analyses revealed the presence of titanium, oxygen, carbon,
      and nitrogen in all implant groups. The blasted-fluoride group revealed fluoride,
      and the blasted-nano HA group calcium and phosphorus with simultaneous decrease
      of titanium and oxygen. Removal torque values revealed an increased retention for
      the chemically modified implants that exhibit specific nanotopography. The
      histologic analyses demonstrated immature bone formation in contact with the
      implant surface in all groups, according to the healing period of the experiment.
      CONCLUSION: Chemical modifications used in the present study were capable of
      producing a particular nanotopography, and together with the ions present at the
      implant surface, may explain the increased removal torque values after a healing
      period of 4 weeks.

PMID- 18807560
TI  - Strain development in 3-unit implant-supported CAD/CAM restorations.
AB  - PURPOSE: Passive fit is difficult to achieve in implant-supported restorations
      with existing superstructure fabrication techniques. The aim of the study
      presented was to investigate whether computer-generated fixed partial dentures
      (FPDs) based on optical impressions lead to less strain development than
      conventionally fabricated FPDs. MATERIALS AND METHODS: A measurement model with 2
      implants was set up and strain gauges were attached to the model material
      mesially and distally adjacent to the implants. Two groups of conventional
      cementable restorations based on repositioning and pick-up impressions,
      respectively, and 1 group of CAD/CAM-generated FPDs based on optical impressions
      were fabricated (n = 10). Strain development during FPD fixation was recorded. In
      order to compare the different FPD groups with one another, a multivariate
      analysis of variance (MANOVA) was performed at a level of significance of alpha =
      .05. RESULTS: The mean strain development at the different strain gauge locations
      ranged from 80.38 microm/m to 437.11 microm/m. The 2 groups of conventionally
      fabricated FPDs showed no significant difference in terms of strain development
      (P = .07). The CAD/CAM-fabricated FPDs revealed a significantly lower strain
      development than those made from pick-up technique impressions (P = .01). No
      significant difference could be detected between the FPDs manufactured from
      repositioning technique impressions and the CAD/CAM-generated restorations (P =
      .19). CONCLUSION: Within the limitations of the study presented, it can be
      concluded that restorations fabricated on the basis of optical impressions
      demonstrate a level of fit which is at least as passive as that of conventional
      FPDs.

PMID- 18807561
TI  - Osseointegrated implant failure associated with MMP-1 promotor polymorphisms (
      1607 and -519).
AB  - PURPOSE: Two polymorphisms in the promoter region of human MMP-1 gene, an
      insertion of a guanine at position -1607 and A-519G substitution, have been shown
      to increase the transcriptional activity of these matrix metalloproteinases
      (MMPs). The objective of this study was to investigate the possible relationship
      between these polymorphisms and early implant failure. MATERIALS AND METHODS: A
      sample of 104 nonsmokers was divided into 2 groups: a test group comprising 44
      patients with 1 or more early failed implants and a control group consisting of
      60 individuals with 1 or more healthy implants. Genomic DNA from oral mucosa was
      amplified by polymerase chain reaction and analyzed by restriction endonucleases.
      The significance of the differences in observed frequencies of polymorphisms were
      assessed by chi2 tests. RESULTS: The G-1607GG polymorphism with the genotype G/G
      was observed at a frequency of 62% in the control group, while in the test group
      this genotype was noted in 34% of the individuals (P = .011). The allele G was
      found at a frequency of 75% in control group and 61.66% in the test group (P =
      .05). No significant differences were seen in the genotypes and allele
      frequencies in the A-519G polymorphism among the groups (P = .064 and P = .124,
      respectively). The distribution of the haplotypes arranged as alleles and
      genotypes showed a significant difference between control and test groups (P =
      .031 and P = .002, respectively). CONCLUSION: On the basis of this study of 60
      patients who experienced no implant failure and 44 patients who experienced
      implant failure, the results suggest that G-1607GG polymorphism in MMP-1 gene is
      associated with early implant failure, while A-519G polymorphism in MMP-1 gene
      does not show a significant relationship with implant loss. This study also
      suggests that haplotypes G-1607GG and A-519G of MMP-1 may be associated with the
      osseointegration process.

PMID- 18807562
TI  - Effect of a multiphasic anodic spark deposition coating on the improvement of
      implant osseointegration in the osteopenic trabecular bone of sheep.
AB  - PURPOSE: Anodic spark deposition techniques have been effectively applied to
      achieve a microporous morphology on metals. To investigate the effect of a new
      anodic spark deposition-based treatment in the enhancement of titanium implant
      osseointegration in trabecular bone of aged and ovariectomized sheep, a
      histomorphometric and microhardness study was carried out. MATERIALS AND METHODS:
      Ten sheep were divided into 2 groups. Five were submitted to a bilateral
      ovariectomy to induce an estrogen-deficiency osteopenia (Ovariectomized), and 5
      were left untreated (Aged). Twenty-four months later, they underwent a bilateral
      implantation of commercially pure titanium screw threads in the lateral surface
      of femoral condyles: electrochemically treated titanium (SP) and acid-etching
      treated titanium (BioRough). Twelve weeks after the second operation, the animals
      were sacrificed and femur segments and iliac crest biopsy specimens were examined
      for histomorphometric and microhardness evaluations. RESULTS: The
      histomorphometry of the trabecular bone of the iliac crest biopsy specimens and
      that around screws showed marked signs of bone rarefaction in the Ovariectomized
      group when compared to the Baseline and Aged groups. Significantly greater bone
      implant contact was observed for SP implants in comparison with BioRough implants
      in both the Aged (P < .001) and Ovariectomized (P < .01) groups. No significant
      differences in terms of microhardness were found between SP and BioRough implants
      within the Aged group, while a significantly higher Bone Maturation Index was
      observed for SP in the Ovariectomized group (P < .05). CONCLUSIONS: The novel
      electrochemical treatment SP produced the most promising results and was able to
      introduce substantial improvements in achieving the fast and stable
      osseointegration of implants in osteopenic bone.

PMID- 18807563
TI  - Implant cast accuracy as a function of impression techniques and impression
      material viscosity.
AB  - PURPOSE: The aim of this study was to compare implant cast accuracy as a function
      of impression technique, closed tray impressions using indirect, metal impression
      copings at the implant level or direct, plastic impression caps at the abutment
      level, and impression material viscosity combinations. MATERIALS AND METHODS: A
      stainless steel master model with three implant replicas was utilized to produce
      Type IV stone casts. Master model impressions were made using closed trays at the
      implant level with screw-on metal impression copings (indirect/implant level) or
      at the abutment level with snap-on plastic impression caps (direct/abutment
      level). With both techniques, either medium-body or heavy-body polyether
      impression material was syringed around the implant impression coping or abutment
      impression cap with medium body material in a custom tray. Twenty casts were
      produced with 5 casts in each test group. A measuring microscope (0.001 mm
      accuracy) was used to measure cast inter-implant or inter-abutment distances.
      Cast accuracy was calculated based on the percent difference of the measurements
      as compared to the master model. RESULTS: A repeated measures 2-factor ANOVA
      (alpha = .05) indicated no significant difference in cast accuracy as a function
      of impression viscosity. However, cast accuracy was significantly different
      between casts made with indirect/implant level versus direct/abutment level
      impressions. With the plastic impression caps, the cast inter-abutment distances
      were larger than the master model, with mean percent differences of 0.19% to
      0.24% across the 3 measurement sites. In contrast, with the metal impression
      coping impressions, the cast inter-implant distances were almost equal to or
      slightly smaller than the master model, with mean percent differences -0.06% to
      0.02%. CONCLUSIONS: Impression material viscosity does not appear to be a
      critical factor for implant cast accuracy. However, casts made with indirect,
      metal impression copings might be more accurate than casts made with direct,
      plastic impression caps. This could be an especially important factor with casts
      used to fabricate multiple-implant restorations.

PMID- 18807564
TI  - The effect of titanium surface roughening on protein absorption, cell attachment,
      and cell spreading.
AB  - PURPOSE: The purpose of this study was to compare properties of roughened and
      polished titanium with respect to their ability to attach to cells and bind to
      protein as well as their cell spreading behavior. MATERIALS AND METHODS: Three
      different titanium surface treatments were compared for their ability to support
      cell attachment and spreading: sandblasted and acid-etched, resorbable blast
      media, and machine-polished titanium. The surface of the materials was
      characterized for surface roughness, surface energy, and surface chemistry.
      Osteoblast-like MG-63 cells were tested for in vitro attachment and spreading in
      the presence of serum proteins. Cell attachment was assessed by direct counting,
      dye binding, and microculture titanium assays. Cell spreading was determined by
      measuring area/cell in phalloidin-AlexaFluor 488 stained cells. Absorption of
      bovine serum albumin was determined by assay. RESULTS: Scanning electron
      micrography and x-ray diffractometry confirmed increased surface roughness of the
      roughened materials. All 3 materials had similar albumin binding kinetics. Three
      different methods confirmed that roughened surfaces enhance early cell attachment
      to titanium in the presence of serum. Cells spread better on smoother machined
      surfaces than on the roughened surfaces. CONCLUSION: Roughened titanium surfaces
      exhibited better early cell attachment than smooth surfaces in the presence of
      serum. The cells attached to roughened titanium were less spread than those
      attached to machined titanium. Although albumin binding was not different for
      roughened surfaces, it is possible that roughened surfaces preferentially bound
      to serum adhesive proteins to promote early cell attachment.

PMID- 18807565
TI  - Abutment screw loosening in single-implant restorations: a systematic review.
AB  - PURPOSE: The purpose of this study was to systematically review clinical studies
      on the incidence of abutment screw loosening in single-implant restorations with
      different implant-abutment connection geometries. MATERIALS AND METHODS: The
      literature search was conducted using several electronic databases. Specific
      terms were used for the database search, which spanned the years 1990 to 2006.
      The search was augmented by using the option of "related articles" as well as
      hand searching of references and relevant journals. Relevant studies were
      selected according to predetermined inclusion and exclusion criteria. Agreement
      between reviewers was determined by using Cohen's kappa coefficients. Three-year
      complication-free rates (survival proportions) were calculated with the aid of a
      survival function, assuming constant failure rates. Summary estimates per group
      for complication-free rate after 3 years (M-estimator) were calculated using
      Tukey's biweight estimator. RESULTS: The initial database search yielded 1,526
      relevant titles. After the subsequent filtering process, 27 studies were finally
      selected. Interexaminer agreement ranged from good to perfect. The external
      connection group comprised 12 studies following 586 single-implant restorations
      for a mean follow-up time that ranged from 3 to 5 years. The estimated percent of
      complication-free single-implant restorations after 3 years was 97.3% (95% CI:
      95.6-98.3). The internal connection group comprised 15 studies following 1,113
      single-implant restorations for a mean follow-up time that ranged from 3 to 10
      years. The estimated percentage of complication-free single-implant restorations
      after 3 years was 97.6% (95% CI: 96.5-98.3). CONCLUSION: The results show that
      abutment screw loosening is a rare event in single-implant restorations
      regardless of the geometry of implant-abutment connection, provided that proper
      antirotational features and torque are employed.

PMID- 18807566
TI  - The zirconia implant-bone interface: a preliminary histologic evaluation in
      rabbits.
AB  - PURPOSE: Zirconia ceramics, a biocompatible material with favorable mechanical
      properties, has been suggested for use in the manufacture of dental implants
      instead of the commonly used titanium. Not much data exist on the early healing
      response around zirconia dental implants. The aim of this study was to give a
      descriptive histologic assessment of the degree of early bone apposition around
      zirconia dental implants at 2 and 4 weeks after insertion compared to surface
      modified titanium implants. MATERIALS AND METHODS: Four zirconia and 4 titanium
      implants were placed in New Zealand white male rabbits. One implant was inserted
      in the condyle of each distal femur. Specimens were harvested at 2 and 4 weeks
      and processed with light microscopic analysis. The area of bone-implant contact
      was evaluated histomorphometrically. RESULTS: A high degree of bone apposition
      could be observed on all implants at both time points. Differences in the
      percentage of implant surface covered with bone were noted between the 2 time
      points, with comparable results for the 2 materials. CONCLUSION: The results of
      this limited histologic study demonstrate a similar rate of bone apposition on
      zirconia and surface-modified titanium implant surfaces during early healing. To
      confirm these results, further studies need to be conducted, involving larger
      sample size at more time points.

PMID- 18807567
TI  - Five-year prospective evaluation of mandibular overdentures retained by two
      microthreaded, TiOblast nonsplinted implants and retentive ball anchors.
AB  - PURPOSE: The aim of this 5-year prospective evaluation was to assess the bone and
      peri-implant mucosa responses at unsplinted, microthread implants supporting
      mandibular overdentures and to determine patient responses to therapy. MATERIALS
      AND METHODS: Two implants were placed by a 1-stage procedure in the
      parasymphyseal mandibles of 59 subjects. Implant placement was followed by
      immediate insertion of overdentures without connection to abutments. After 3
      months, connection using Dalla Bona attachments was made and peri-implant mucosa,
      peri-implant bone, and patient perceptions of treatment were evaluated. RESULTS:
      The implant success rate was 95.9% from 6 to 60 months. The changes in marginal
      bone levels were positive (bone gain) but did not reach statistical significance
      at 12, 36, or 60 months (+0.13 +/- 0.59 mm, +0.23 +/- 0.66 mm, and +0.09 +/-
      0.79, respectively). Treatment was viewed as effective; patients rating
      satisfaction with their teeth increased from a preoperative level of 12.1% to
      94.6% at overdenture abutment connection and remained high (81.6%) after 5 years.
      CONCLUSIONS: Expedited mandibular overdenture therapy utilizing unsplinted,
      microthreaded mandibular parasymphyseal implants was associated with high implant
      survival, preservation of crestal bone, and high patient satisfaction.
      Complications were minor and related to prosthodontic features of therapy.

PMID- 18807568
TI  - Multicenter retrospective study of cement-retained implant-supported anterior
      partial prostheses: success and restoration evaluation.
AB  - PURPOSE: The aim of this multicenter study was to evaluate implant success and
      restorative complications of cement-retained implant-supported anterior partial
      prostheses in Jordan. MATERIALS AND METHODS: A retrospective study of all
      implants with a minimum of 1-year follow-up were used to support fixed, cement
      retained restorations from April 2000 until March 2007. The cement-retained
      implants were loaded with either single- or multiple-tooth replacements. The
      Fisher exact test was performed to test the presence of any statistically
      significant difference in success concerning gender or arch of placement.
      RESULTS: Eighty-seven implants were placed in the anterior region of the mandible
      or maxilla in 49 patients at multiple clinical practices in Jordan. The age of
      the patients ranged from 17 to 85 years. Eighteen implants were placed in the
      mandible and 69 in the maxilla. Three maxillary implants in 2 male patients had 3
      mm horizontal bone loss. Those 3 implants are still functioning and were
      considered surviving implants but not successful implants. Therefore, the implant
      cumulative survival rate for both arches and genders was 100%. The implant
      cumulative success rate was 95.78%. Three crowns (maxillary) were dislodged. No
      significant differences were revealed regarding gender or arch of placement (P >
      .05). CONCLUSIONS: Cement-retained implants exhibited high survival and success
      rates among a Jordanian population.

PMID- 18807569
TI  - Immediate nonfunctional loading of single-tooth implants in the anterior maxilla
      following augmentation with freeze-dried cancellous block allograft: a case
      series.
AB  - PURPOSE: To assess the clinical effectiveness of immediate nonfunctional loading
      for single-tooth implants placed in the anterior maxilla following augmentation
      with cancellous freeze-dried block graft. MATERIALS AND METHODS: The clinical
      outcomes of immediately nonfunctionally loaded implants up to 18 months after
      placement in the anterior maxilla were evaluated in 11 consecutive patients.
      Implants were immediately restored with unsplinted acrylic resin provisional
      crowns. Follow-up was monthly, and intraoral radiographs were obtained
      immediately after implant placement and at 6, 12, and 18 months. Survival rate
      and radiographic marginal bone loss were evaluated at 0, 6, 12, and 18 months. In
      the anterior maxilla, 12 implants were placed. RESULTS: Marginal bone loss did
      not extend beyond the first thread up to 18 months follow-up, and the survival
      rate was 100%. CONCLUSION: Within the limits of the present study, immediate
      nonfunctional loading for single-tooth implants placed in the anterior maxilla
      following augmentation with cancellous freeze-dried block graft seems a promising
      treatment alternative.

PMID- 18807570
TI  - Provisional implants for immediate restoration of partially edentulous jaws: a
      clinical study.
AB  - PURPOSE: The aim of this study was to evaluate the use of provisional implants,
      which can provide patients with provisional fixed partial dentures during the
      healing time of augmentation procedures and/or during the osseointegration period
      of definitive implants until delivery of the definitive prosthesis. MATERIALS AND
      METHODS: Thirty-one patients were consecutively included in the study. Eighteen
      patients (group A, primary simultaneous group) were initially treated
      simultaneously with provisional and definitive implants and provided with 18
      interim fixed partial dentures. Thirteen patients (group B) received provisional
      implants in a staggered procedure. In the first stage of group B patients
      (augmentation phase), provisional implants were placed to bridge the augmentation
      phase and for anchoring 13 interim fixed partial dentures. In the second stage
      (secondary simultaneous group), patients of group B received provisional implants
      to bridge the osseointegration phase for simultaneously placed definitive
      implants by further use of 13 interim fixed partial dentures. All patients were
      followed from provisional implant and definitive implant placement to delivery of
      the definitive prosthesis. Loss of provisional implants and interim fixed partial
      dentures was noted, and stability of provisional implants was evaluated using the
      Periotest device. The procedures of immediate rehabilitation with fixed partial
      dentures using provisional implants were subjectively rated by patients with
      regard to satisfaction, treatment period, and acceptance. RESULTS: In 31
      patients, 44 provisional fixed partial dentures were supported by 98 provisional
      implants. No provisional implant loss in group A or group B-second stage was
      observed. Only 3 (3%) provisional implants were lost in group B-first stage
      during the augmentation phase. Incidence (90.8% versus 9.2%) and stability
      (Periotest values: 8.6 +/- 3.9 versus 4.8 +/- 2.7) of provisional implants
      differed significantly between maxilla and mandible (P < .01). All interim fixed
      partial dentures (n = 44) remained in place for the intended time period but in 3
      cases with provisional implant loss they were shortened. No definitive implant
      loss (n = 94, survival: 100%) and especially no implant loss in cases of
      maxillary sinus augmentation was seen. The items rated showed high satisfaction
      and good acceptance of the intensive surgical and prosthodontic program.
      CONCLUSION: This clinical review showed that (1) provisional implants can
      successfully provide patients with a fixed partial denture for immediate
      rehabilitation to bridge the osseointegration or augmentation phase, even in
      cases with an initially compromised bone situation and (2) although treatment is
      elaborate, the selected patients decided on a fixed interim rehabilitation with
      provisional implants rather than on a removable solution.

PMID- 18807571
TI  - A retrospective analysis of sandblasted, acid-etched implants with reduced
      healing times with an observation period of up to 5 years.
AB  - PURPOSE: The aim of this study was to evaluate the success rate of 2 different
      implant systems with sandblasted and acid-etched modified surfaces loaded after
      reduced healing periods. MATERIALS AND METHODS: One-hundred seventeen patients
      with a mean observation period of 3.75 years (24 to 61 months) were included in
      this evaluation. Chart reviews of a standardized recall program were evaluated.
      All 532 placed implants showed an unloaded healing time of 6 weeks in the
      mandible and 12 weeks in the maxilla. At abutment placement a torque value of 35
      Ncm was one of the primary variables, and the success of the implants over time
      was determined by the criteria of Buser et al. The survival was analyzed using
      Kaplan-Meier method, and the probability of an event within 1 group independent
      of time was evaluated using the chi-square test and Fisher exact test. RESULTS:
      Of the 532 implants, 235 were placed in female and 297 in male patients; 448
      implants were located in the maxilla and 84 in the mandible. Three implants were
      lost prior to abutment connection in 3 patients. Life table analyses show an
      overall success rate of 99.4% at 5 years, as no implants were lost after abutment
      connection. There was no significant association of the implant type (P = .185),
      gender (P = .99), or jaw (maxilla/mandible; P = .06) and the survival of the
      implants within this study. CONCLUSION: Based on the data found in this
      investigation, it can be concluded that implants with sandblasted, acid-etched
      surfaces can be restored after a 6- to 12-week healing period with a high
      predictability of success.

PMID- 18807572
TI  - Clinical outcome and patient satisfaction following full-flap elevation for early
      and delayed placement of single-tooth implants: a 5-year randomized study.
AB  - PURPOSE: This 5-year follow-up report presents the outcome of early and delayed
      placement of single-tooth implants. MATERIALS AND METHODS: An implant was placed
      on average 10 days after tooth extraction in 23 patients (early) and 3 months
      after tooth extraction in 22 patients (delayed). All implants were placed in the
      anterior or premolar regions of the maxilla or mandible. Survival rates,
      prosthodontic complications, probing pocket depths (PPDs), marginal bone levels
      measured on radiographs (MBLs), soft tissue appearance (papilla dimensions and
      clinical crown height), and patient satisfaction were evaluated during an
      observation period of 5 years. Several patients with prior generalized gingival
      recession were included in the study, and modification of the papilla scoring was
      made in these cases. RESULTS: Two implants in the early group and 1 in the
      delayed group failed before occlusal loading. No further implants were lost
      during the follow-up period. The mean PPD varied from 3.3 to 4.5 mm in the early
      group and from 3.6 to 4.4 mm in the delayed group 5 years after implant
      placement. During the 5-year period, an annual marginal bone loss of less than
      0.2 mm was found in both groups. Although the early group performed slightly
      better than the delayed group as to soft tissue appearance just after seating of
      the implant restoration, the papilla dimensions and the clinical crown height
      improved spontaneously over time, and no significant differences between the 2
      protocols were seen after 5 years. Furthermore, patients in both groups were
      highly satisfied with the outcome of their implant treatment. CONCLUSION: The
      outcomes of early and delayed placement of single-tooth implants were comparable
      in terms of high survival rates, few prosthetic complications, acceptable MBLs
      and PPDs, as well as soft tissue appearance and patient satisfaction during a 5
      year follow-up period.

PMID- 18807573
TI  - Conventional and advanced implant treatment in the type II diabetic patient:
      surgical protocol and long-term clinical results.
AB  - PURPOSE: To investigate the effect of type-2 diabetes on implant survival and
      complication rate. MATERIALS AND METHODS: Prospective study enrolling type-2
      diabetic patients suffering from edentulism, having a mean perioperative HbA1c
      level of 7.2%, and compliant with a maintenance program. All the patients
      underwent dental and periodontal examinations and had laboratory testing for
      HbA1c, fasting plasma glucose, blood lipids, and microalbuminuria. Nondiabetic
      patients matched for implant treatment indication served as controls. The
      influence of clinical diabetes-related factors and periodontal parameters (Plaque
      Index, bleeding on probing, probing depth) on implant survival were assessed via
      univariate then multivariate methods. RESULTS: Forty-five diabetic patients,
      followed for 1 to 12 years, mean age 64.7 years, received 255 implants: 143
      following a classical protocol and 112 in cases of sinus floor elevation,
      immediate loading, and guided bone regeneration. Forty-five nondiabetic control
      patients received 244 implants: 142 following a classical protocol and 102 in
      cases of advanced surgery. Implant survival following conventional or advanced
      implant therapy was not statistically different between the well-controlled
      (HbA1c < 7%, P = .33) and the fairly well-controlled group (HbA1c 7% to 9%, P =
      .37). The overall survival rate for the diabetic group was 97.2% (control 98.8%)
      and was not significantly different for age, gender, diabetes duration, smoking,
      or type of hypoglycemic therapy. The mean peri-implant bone loss was 0.41 +/-
      0.58 mm (control, 0.49 +/- 0.64 mm). PI and BOP fairly correlated with
      postoperative complications. HbA1c was the only multivariate independent factor
      affecting the complication rate (P = .04). No statistically significant
      difference was found for patients (P = .81) or for implants (P = .66) for the
      advanced surgery cases or the conventional approach in diabetic patients compared
      to nondiabetic patients.

PMID- 18807574
TI  - Immediate versus delayed loading of dental implants placed in fresh extraction
      sockets in the maxillary esthetic zone: a clinical comparative study.
AB  - PURPOSE: The aim of this study was to report a clinical comparative assessment of
      crestal bone level change around single implants in fresh extraction sockets in
      the esthetic zone of the maxilla either immediately loaded or loaded after a
      delay. MATERIALS AND METHODS: Forty patients were included in a prospective,
      randomized study. All patients required 1 tooth extraction (ie, 1 tooth with a
      hopeless prognosis) and were randomized into either the test group or the control
      group. Implants were positioned immediately after tooth extraction and were
      loaded immediately in the test group (20 implants) and after 3 months in the
      control group (20 implants). The implant site was prepared, with at least 4 mm of
      sound apical bone below the implant apex, and the coronal margin of the implant
      was placed at the buccal level of the bone crest. All implants were 13 mm long;
      30 implants had a diameter of 5 mm, and 10 had a diameter of 3.75 mm.
      Radiographic examinations were made at baseline, at 6 months, and at 24 months.
      To compare the mean values between test and control group, a paired t test was
      performed (considered statistically significant at P < .05). RESULTS: After a 24
      month follow-up period, a cumulative survival rate of 100% was reported for all
      implants. The control group resulted in a mean mesial bone loss of 1.16 +/- 0.32
      mm and a mean distal bone loss of 1.17 +/- 0.41 (mean bone loss, 1.16 +/- 0.51
      mm). The test group resulted in a mesial bone loss of 0.93 +/- 0.51 mm and a
      distal bone loss of 1.1 +/- 0.27 mm (mean bone loss, 1.02 +/- 0.53 mm). No
      statistically significant difference between control and test groups (P > .05)
      was found. CONCLUSION: The success rate and radiographic results of immediate
      restorations of dental implants placed in fresh extraction sockets were
      comparable to those obtained in delayed loading group.

PMID- 18807575
TI  - Optimization in multi-implant placement for immediate loading in edentulous
      arches using a modified surgical template and prototyping: a case report.
AB  - Immediate loading of dental implants shortens the treatment time and makes it
      possible to give the patient an esthetic appearance throughout the treatment
      period. Placement of dental implants requires precise planning that accounts for
      anatomic limitations and restorative goals. Diagnosis can be made with the
      assistance of computerized tomographic scanning, but transfer of planning to the
      surgical field is limited. Recently, novel CAD/CAM techniques such as
      stereolithographic rapid prototyping have been developed to build surgical guides
      in an attempt to improve precision of implant placement. The aim of this case
      report was to show a modified surgical template used throughout implant placement
      as an alternative to a conventional surgical guide.

PMID- 18807576
TI  - Bioequivalence study of two different film-coated tablet formulations of losartan
      hydrochlorothiazide in healthy volunteers.
AB  - The study was conducted in order to assess the bioequivalence of two film-coated
      formulations containing 100 mg of losartan (CAS 124750-99-8) and 12.5 mg of
      hydrochlorothiazide (CAS 58-93-5). Seventy-three healthy subjects were enrolled
      in a randomised, single-dose, open-label, two-way crossover study, with a minimum
      washout period of 7 days. A total of 21 blood samples were collected up to 36 h
      post-dosing. Losartan, losartan carboxy acid and hydrochlorothiazide levels were
      determined by liquid chromatography with tandem mass detection (lower limit of
      quantification: 1.01 ng/mL for hydrochlorothiazide, 2.02 ng/mL for losartan and
      2.51 ng/mL for losartan carboxy acid). Pharmacokinetic parameters used for
      bioequivalence assessment (AUC(0-t) and Cmax as primary and AUC(0-inf) as
      secondary pharmacokinetic parameters) were determined from the losartan and
      hydrochlorothiazide concentration data using non-compartmental analysis. Data
      from losartan carboxy acid was reported and presented as supportive data. The 90%
      confidence intervals (obtained by ANOVA) for losartan were 97.05-118.48% for Cmax
      100.76-106.10% for AUC(0-t) and 100.80-106.10% for AUC(0-inf) whereas for
      hydrochlorothiazide the 90% confidence intervals obtained were 103.94-115.33% for
      Cmax, 101.97-109.61% for AUC(0-t) and 101.77-109.02% for AUC(0-inf), and for
      losartan carboxy acid the intervals obtained were 98.31-107.82% for Cmax, 97.89
      104.30% for AUC(0-t) and 98.06-104.30% for AUC(0-inf). All the 90% confidence
      intervals obtained for all the parameters assessed were within the predefined
      ranges (80-125%). Based on these results, it can be concluded that the evaluated
      formulations are bioequivalent in terms of rate and extent of absorption.

PMID- 18807577
TI  - Effects of D-003, a mixture of sugarcane wax acids, on platelet aggregation in
      hypercholesterolemic patients. A dose-titration, randomised, placebo-controlled
      trial.
AB  - Increased platelet aggregation contributes to vascular risk. D-003, a mixture of
      high molecular weight sugarcane wax acids, has shown antiplatelet effects in
      experimental models and healthy volunteers. This randomised, double-blinded,
      placebo-controlled study investigated the effects of titrated doses of D-003 (5
      20 mg/d) on platelet aggregation in hypercholesterolemic patients. After a 4-week
      baseline phase, 56 patients were randomised to D-003 5 mg/d or placebo. The doses
      were doubled every 15 days if arachidonic acid (AA)-induced platelet aggregation
      was not inhibited at least by 15%. AA (0.75 and 1.5 mmol/L) and collagen (1
      microg/mL)-induced platelet aggregation, laboratory and physical safety
      indicators were assessed at baseline and every 15 days thereafter, when adverse
      events (AE) were also reported. No significant change of platelet aggregation was
      found in the placebo group. After 15, 30 and 45 on therapy, D-003 reduced
      platelet aggregation induced with both AA 0.75 mmol/L (18.1%, 19.0% and 30.3%,
      respectively) and AA 1.5 mmol/L (17.0%, 16.3% and 22.5%, respectively), and also
      collagen-induced platelet aggregation (26.6%, 20.8% and 29.4%) (p < 0.01 at days
      15 and 30 versus placebo, p < 0.0001 at study completion). The mean inhibition of
      platelet aggregation with D-003 at day 15, at which all patients had received the
      lowest dose, was over 15%. Nineteen out of 28 D-003 randomised patients (67.9%)
      required dose titration to achieve such goal. At trial completion, the mean
      estimated dose was 11.6 mg/d. D-003 lowered low-density lipoprotein (22.0 %),
      total cholesterol (14.7%) and raised high-density lipoprotein-cholesterol (10.9%)
      (p < 0.0001 versus placebo). Six patients (2 placebo, 4 D-003) withdrew from the
      trial, none due to AE. D-003 did not modify the safety indicators with respect to
      placebo. Four patients (2 placebo, 2 D-003-treated) reported AE: pruritus and
      increased blood pressure (2 placebo) and rash and polyphagla (2 D-003). In
      conclusion, D-003 (5-20 mg/d) given as doses titrated every 15 days (5-20 mg/d)
      inhibited AA- and collagen-induced platelet aggregation in hypercholesterolemic
      patients and was well tolerated.

PMID- 18807578
TI  - Bioequivalence study of two capsule formulations of omeprazole in healthy
      volunteers.
AB  - The study was conducted in order to assess the bioequivalence of two capsule
      formulations (test and reference) containing 20 mg of omeprazole (5-methoxy-2-[[4
      methoxy-3,5-dimethyl-2-pyridinyl) methyl]sulfinyl]-1H-benzimidazole, CAS 73590-58
      6). Fifty healthy male and female volunteers were treated in a single-centre,
      randomised, repeated-dose (once daily for six consecutive days), open-label, two
      way crossover study, with a washout period of at least 9 days between treatments.
      Plasma samples were collected up to 12 h post-dosing for the determination of
      omeprazole by HPLC with photodiode array detector (DAD). The evaluation of
      bioequivalence was based on the following pharmacokinetic parameters that were
      calculated by standard non-compartmental methods: area under the plasma
      concentration-time curve from zero to the time of the last quantifiable
      concentration (AUCt) and that extrapolated to infinity (AUC) and the
      maximumobserved concentration (Cmax). The 90% confidence interval around the
      ratios (test/reference) (obtained by analysis of variance, ANOVA) were 0.92-1.04
      forCmax, 0.88-1.05 for AUCt, and 0.88-1.05 for AUC, i.e., within the predefined
      acceptable range for the conclusion of bioequivalence. The study indicated that
      the test and reference formulations containing 20 mg of omeprazole are
      bioequivalent in terms of both the rate and extent of bioavailability.

PMID- 18807579
TI  - Effects of oral supplementation with iron(III) hydroxide polymaltose complex on
      the hematological profile of adolescents with varying iron status.
AB  - OBJECTIVE: To assess the effects of supplementation with oral iron(III) hydroxide
      polymaltose complex on the iron status of adolescents with and without iron
      deficiency and anemia. METHOD: Adolescents of both sexes with varying iron status
      were allocated to four treatment groups by using inclusion criteria. Three of the
      four groups received iron(III) hydroxide polymaltose complex (IPC, Maltofer)
      containing 100 mg of iron 6 days a week for 8 months. The fourth group was given
      a placebo. Hematological parameters were assessed at the baseline and after 4 and
      8 months of supplementation. RESULTS: IPC supplementation resulted in a
      significant increase in iron parameters in all the three supplemented groups
      including correction of iron deficiency and anemia along with improvement in
      storage iron after 8 months. No side effects were noted in any of the
      supplemented subjects. CONCLUSIONS: IPC supplementation improved the iron status
      of adolescents with and without iron deficiency and anemia. These data provide
      evidence that IPC is an easy-to-administer and well tolerated compound which can
      improve and normalize the iron status of iron deficient and anemic patients.

PMID- 18807580
TI  - Synthesis and evaluation of analgesic, anti-inflammatory and antioxidant
      activities of new 6-acyl-3-alkyl-5-methyl-2(3H)-benzoxazolones.
AB  - A new series of 6-acyl-3-alkyl-5-methyl-2(3H)-benzoxazolones have been obtained
      starting from 5-methyl-2(3H)-benzoxazolone. All the compounds have been
      characterized by IR, 1H-NMR and mass spectroscopy. The new compounds were
      screened for analgesic and anti-inflammatory activities and ulcerogenic effect.
      The in vitro antioxidant capacity of the synthesized compounds were tested by the
      nitric oxide radical scavenging assay. Most of the compounds showed
      antiinflammatory activity. Among them, 3-[4-(4-fluorophenyl)piperazinomethyl] -6
      (3-chlorobenzoyl)-5-methyl-2(3H)-benzoxazolone (3j) was found more potent than
      the reference drug indometacin (CAS 53-86-1) with 41.66% decrease in edema.
      Compared with the control, some of the compounds exhibited analgesic effects.
      Similar to the anti-inflammatory activity results, compound 3j showed the highest
      analgesic profile with 48.56% inhibition. No active hemorragic focus was observed
      in the microscopic evaluation in the ulcerogenic effect studies of the tested
      compounds. 6-(3-Chlorobenzoyl)-5-methyl-2(3H)-benzoxazolone (2b) and 3-[4-(4
      fluorophenyl-piperazino)methyl]-6-(3-chlorobenzoyl)-5-methyl-2(3H)-benzoxazolone
      (3j) showed nearly maximum antioxidant activity compared to ascorbic acid (CAS 50
      81-7) with IC50 values of 27.6 and 30.1 microg/mL, respectively.

PMID- 18807581
TI  - Bioequivalence study of two capsule formulations containing diacerein 50 mg in
      healthy human subjects.
AB  - This study presents the results of a two-way, two-period, two-treatment crossover
      investigation in 12 healthy Indian male subjects to assess the bioequivalence of
      two oral formulations containing 50 mg of diacerein (CAS 13739-02-1). Both
      formulations were administered orally as a single dose separated by a one-week
      washout period. The content of diacerein in plasma was determined by a validated
      HPLC method with UV detection. The formulations were compared using the
      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)), peak
      plasma concentration (Cmax), and time to reach peak plasma concentration (tmax).
      The results of this study indicated that there were no statistically significant
      differences between the logarithmically transformed AUC(0-infinity) and Cmax,
      values of the two preparations. The 90% confidence interval for the ratio of the
      logarithmically transformed AUC(0-t), AUC(0-infinity) and Cmax were within the
      bioequivalence limit of 0.8-1.25 and the relative bioavailability of the test
      formulation was 96.63% of that of the reference formulation. Thus, these findings
      clearly indicate that the two formulations are bioequivalent in terms of rate and
      extent of drug absorption.

PMID- 18807582
TI  - Pharmacokinetics and excretion of the novel anti-tuberculosis compound 1,2:5,6-di
      O-isopropylidene-3-O-(phenyl cyclopropyl methanonyl)-alpha-D-glucofuranose (S-001
      14) after oral doses in rats. Development of a sensitive and reproducible high
      performance liquid chromatography-UV method for the determination of the test
      compound in rat serum.
AB  - A sensitive and reproducible high performance liquid chromatography (HPLC)-UV
      method for the determination of the novel anti-tuberculosis compound 1,2:5,6-di-O
      isopropylidene-3-O-(phenyl cyclopropyl methanonyl)-alpha-D-glucofuranose (S-001
      14) has been developed and validated in rat serum, urine and feces. Following
      extraction with hexane at alkaline pH, samples were separated on a reverse phase
      C18 column and quantified using UV detection at 267 nm. The mobile phase was 70%
      acetonitrile in ammonium acetate buffer (10 mmol/L, pH 6.0) with a flow rate of
      1.0 ml/min. The method was used to determine the pharmacokinetics and excretion
      of S-001-14 after oral doses in rats. Linearity was satisfactory over the
      concentration range of 5-500 ng/ml (r2, > 0.99). Recoveries were > 90% and were
      consistent throughout the calibration range. The precision and accuracy were
      acceptable as indicated by relative standard deviation ranging from 2.72 to
      9.54%, bias values ranging from 1.62 to 12.05%. Moreover, S-001-14 was stable in
      rat serum after being subjected to three freeze-thaw cycles and for 30 days on
      storage at - 60 degrees C. The method was used to determine the serum
      concentration-time profiles for S-001-14 after oral doses of 4, 100 and 200 mg/kg
      in rats. A linear pharmacokinetics was found in rats at 100 and 200 mg/kg doses
      with a long elimination half-life (approximately 24 h), wide distribution and
      bioavailability of approximately 13%. The excretion study after the 100 mg/kg
      oral dose revealed that S-001-14 was excreted in urine (0.002 +/- 0.001%) and
      feces (15.6 +/- 3.5%).

PMID- 18807583
TI  - Bioequivalence study of two letrozole tablet formulations. Single dose,
      randomized, open-label, two-way crossover bioequivalence study of letrozole 2.5
      mg tablets in healthy volunteers under fasting conditions.
AB  - The study was conducted in order to compare the bioavailability of two tablet
      formulations containing letrozole 2.5 mg (CAS 112809-51-5). Twenty healthy
      subjects were enrolled in a single-centre, bioequivalence, randomised, single
      dose, open-label, two-way crossover study, performed under fasting conditions
      with a minimum washout period of 21 days. Plasma samples were collected up to 240
      h post-dosing. Letrozole levels were determined by reverse liquid chromatography
      and detected by tandem mass spectrometry detection, LC/MS/MS method.
      Pharmacokinetic parameters used for bioequivalence assessment, area under the
      concentration-time curve from time zero to time of last non-zero concentration
      (AUC(0-t)) and from time zero to infinitive (AUC(0-inf)) and maximum observed
      concentration (Cmax), were determined from the letrozole concentration data using
      non-compartmental analysis. The 90% confidence intervals obtained by analysis of
      variance were 90% geometric confidence Intervals of the ratio (A/B) of least
      squares means from the analysis of variance (ANOVA) of the In-transformed AUC(0
      t), and Cmax was within 80% to 125%. Bloequivalence between formulations was
      concluded both in terms of rate and extent of absorption.

PMID- 18807584
TI  - PSivida corporation.

PMID- 18807585
TI  - Why should we be interested in the defence of our profession?

PMID- 18807586
TI  - Peripheral endovascular revascularization trials: high noon for uniform reporting
      standards.
AB  - In the era of evidence based medicine, proof of clinical benefits and cost
      effectiveness need to be firmly based on transparent comparisons between various
      therapeutic alternatives. Standards for reports are a prerequisite for
      comparisons across reports and should reflect the patient's perspective.
      According standards have been successfully introduced in many fields of modern
      medicine, but not yet for peripheral endovascular interventions. Given the
      overwhelmingly increasing importance of endovascular revascularization in
      patients with chronic lower limb ischemia, this report provides an updated
      outline of the heterogeneity of current reporting practice and highlights the
      need for uniform reporting standards.

PMID- 18807587
TI  - Atherosclerotic aneurysms. Comparisons between thoracic stentgrafts--how do we
      know which stent graft to select?
AB  - Surgical intervention for thoracic aortic aneurysms (TAA) greater than six
      centimetres is warranted in most patients deemed fit enough to withstand surgery
      as the annual risk of death, rupture or dissection is estimated to be 16%.
      Traditional surgical repair of thoracic aortic aneurysms however carries an
      attendant risk of significant morbidity and mortality. Endovascular repair
      (TEVAR) has emerged as a feasible alternative which is associated with
      significantly improved patient outcomes even in the highest risk patients.
      Improvement in stent-graft design has increased the rates of technical success of
      aneurysm exclusion and promises to offer further mid-term reductions in the need
      for re-intervention and the risk of aneurysm related death. This review article
      highlights the advances made in thoracic stent-graft design and discusses patient
      outcomes for each of the most widely used endografts in clinical practice to
      date.

PMID- 18807588
TI  - Open surgery for abdominal aortic aneurysm or aorto-iliac occlusive disease-
      clinical and ultrasonographic long-term results.
AB  - OBJECTIVE: To determine postoperative and long-term outcome and assess the
      relevance of abdominal ultrasound (US) after surgery for abdominal aortic
      aneurysm (AAA) or aortoiliac occlusive disease (AIOD). METHODS: Records of 1704
      consecutive patients having graft implantation from 1988 to 2000, either for AAA
      (n = 1144) or for AIOD (n = 560), were reviewed. In 2006, follow-up was 9180
      patients-years for the AAA group and 5450 patients-years for the AIOD group.
      Among 1006 alive patients, 377 were invited randomly for US and clinical
      examination. RESULTS: Hospital death occurred in 99 patients (8.6%) of the AAA
      group (53% in ruptured and 2% in elective AAA), and in 18 patients of the AIOD
      group (3.2%). There were 581 late deaths, including eight due to prosthesis
      infection, one to pseudo-aneurysm rupture, and one to graft thrombosis (0.6%
      graft-related mortality). Prosthesis thrombosis occurred in 32 patients (26 in
      AIOD group, p < 0.001), and graft infection in 26 (17 in AAA group, p < 0.01).
      Pseudoaneurysms developed in 90 patients (68 in AIOD group, p < 0.001), including
      eight at the proximal aortic, one at the distal aortic, two at the iliac and 79
      at the femoral anastomosis. In the AAA group only, surgery was required for a new
      thoraco-abdominal and pararenal aneurysm in eight and four patients,
      respectively, while US evidenced a 26-35 and a 36-50 mm supraanastomotic aortic
      dilatation in 65 (32%) and in 14 (7%) patients, at a mean follow-up of 10.5 and
      9.3 years, respectively. CONCLUSION: Long-term results are good after open
      surgery for AAA or AIOD. Prosthesis infection and anastomotic pseudo-aneurysm are
      the main causes of graft-related mortality and morbidity, respectively. Because
      of high incidence of asymptomatic supraanastomotic aortic dilatation, all
      patients with a history of AAA repair should have regular abdominal US.

PMID- 18807589
TI  - Laparoscopic repair of parastomal hernias: a multi-centre retrospective review
      and shift in technique.
AB  - PURPOSE: To describe the reasons for a shift in our technique of laparoscopic
      repair of parastomal hernias towards repair with a non-slit mesh. Our initial
      results with repair using meshes with a keyhole had high recurrence rates.
      METHODS: We performed a multi-centre retrospective study focusing on
      complications and recurrences. Data were gathered retrospectively from the
      medical records. The last follow-up date was the latest clinical examination by
      the surgeon. Recurrences were diagnosed clinically or by CT scan performed for
      oncological follow-up in cancer patients. RESULTS: From September 2001 till May
      2007, twenty-four patients with a symptomatic parastomal hernia were treated
      laparoscopically. No major intra- or postoperative complications were
      encountered. We had no conversions, no enterotomies and the overall postoperative
      morbidity was 8.4% (2/24). During a mean follow-up of 21.2 months, ten
      recurrences or 41.7% (10/24) have been diagnosed. In patients treated with a
      "keyhole technique" recurrence rate was 72.7% (8/11) with a mean follow-up of
      30.7 months. In patients treated with a "modified Sugarbaker technique"
      recurrence rate was 15.4% (2/13) with a mean follow-up of 14.0 months.
      CONCLUSIONS: We found laparoscopic parastomal hernia repair could be performed
      with few complications. We abandoned the "keyhole techniques" because of a high
      recurrence rate. We currently use a "modified Sugarbaker technique" with
      promising early results.

PMID- 18807590
TI  - Long-term results of a non-ramdomized prospective mono-centre study of 1000
      laparoscopic totally extraperitoneal hernia repairs.
AB  - BACKGROUND: Information concerning short-term results for laparoscopic
      extraperitoneal hernia repair is available, but long-term results remain poorly
      documented. The purpose of this non-randomized prospective study was to evaluate
      recurrence and chronic pain after hernia repair over a period longer than 10
      years. MATERIALS AND METHODS: From 1995 to 2004, all patients aged 30 years or
      more, manifesting with inguinal hernia, were included in our study. Patients aged
      20 to 30 years presenting with bilateral hernia, recurrent hernia, or who were
      heavy workers were also included. Patients who had pelvic irradiation,
      strangulated hernia, prostatic cancer resection, or a contra-indication to
      general anaesthesia were excluded. Of 1096 hernia repairs performed, 248 patients
      were excluded and underwent open repair and 848 patients (77.4%) were included in
      our prospective study, which corresponded to 1000 laparoscopic hernia repairs.
      RESULTS: The sex ratio (male : female) was 5:8, and the average age was 56 years.
      Seven hundred and fifty-three hernias (75.3%) were first repairs, 247 (24.7%)
      were recurrent hernias, and 161 were bilateral hernias. There were no
      mortalities. The conversion rate was 1.1%, and the global postoperative morbidity
      rate was 10.3%. Average follow-up was 39 months in 92.2% of the patients. Hernia
      recurrence rate was 1.5%. Chronic pain occurred in 2.9%. During this follow-up,
      22 contra-lateral hernias appeared in those patients who initially had unilateral
      hernia repair (3.2%). All of these contra-lateral hernias could be successfully
      treated using a laparoscopic total extraperitoneal approach. CONCLUSIONS: The
      long-term results of this study demonstrate that preperitoneal laparoscopic
      hernia repair is a safe technique with a very low recurrence rate and low
      prevalence of chronic pain.

PMID- 18807591
TI  - Impact of ilio-inguinal nerve excision on sexual function in open inguinal hernia
      mesh repair: a prospective follow-up study.
AB  - The aim of this study was to prospectively compare sexual function in patients
      undergoing inguinal hernia surgical repair with or without excision of the ilio
      inguinal nerve. Eighty-four patients (76 males and 8 females) with a unilateral
      inguinal hernia were enrolled in the study. They underwent an open tension free
      repair with mesh implantation ("plug and patch" technique). The ilio-inguinal
      nerve was identified and was either preserved (Preservation group, n = 42) or
      divided (Excision group, n = 42). Patients were asked to answer an anonymous
      standardised questionnaire about their sexual function pre-operatively, 3 months
      postoperatively and every 6 months afterwards during the followup. Thirty-two
      patients (excision group: n = 17 ; preservation group: n = 15 ; p > 0.05)
      reported pre-operative sexual dysfunction related to the groin hernia. Three
      months after surgery 19 patients referred a clear improvement of their
      preoperative complaints. Eleven patients reported new functional problems. About
      20% of the patients in both groups reported an improvement of their pre-operative
      sexual disorders. New sexual functional symptoms were reported significantly more
      in the preservation group compared to the excision group (21% vs. 7%, p < 0.05).
      Twenty-four months after surgery the number of patients with functional sexual
      symptoms was lower in both groups but yet significantly higher in the
      preservation group. In conclusion, neurectomy of the ilio-inguinal nerve during
      surgical repair of inguinal hernia could have a favourable influence on sexual
      function without relevant complications. It causes significantly less sexual
      problems compared to preservation of the nerve and it is recommended especially
      for patients with pre-operative sexual dysfunction due to the groin hernia.

PMID- 18807592
TI  - Temporary abdominal closure with the vacuum pack technique: a 5-year experience.
AB  - The vacuum pack technique is used increasingly for temporary abdominal closure.
      This paper communicates the related experience of the authors. MATERIAL AND
      METHODS: The charts of 74 patients who underwent temporary abdominal closure with
      the vacuum pack technique between January 2000 and December 2005 were reviewed
      retrospectively. The demographic characteristics, mortality rates and long-term
      complications were analysed. RESULTS: The vacuum pack was inserted 139 times to
      74 patients who required temporary abdominal closure. The mortality rate was 60%
      (45/74). Survivors and non-survivors did not differ significantly with respect to
      etiology (traumatic vs. non-traumatic), age, number of re-laparotomies, hospital
      stay, type of closure (primary or with a graft). The frequency of primary fascial
      closure was 45%. The frequency of incisional hernia was 50% in the patients who
      underwent primary closure and 10% in those who underwent graft placement (p <
      0.05). CONCLUSIONS: Temporary abdominal closure with the vacuum pack is a simple
      and inexpensive technique. Primary fascial closure is possible in approximately
      half of the cases ; however, the frequency of incisional hernia is high.

PMID- 18807593
TI  - The application of MR brain surface anatomy scanning in the operation of
      intracranial parasagittal meningiomas.
AB  - PURPOSE: To assess the usefulness of magnetic resonance (MR) brain surface
      anatomy scanning (SAS) in neurosurgery for intracranial parasagittal meningiomas.
      METHODS AND MATERIALS: Pre-operative MR brain SAS was performed on 22 patients
      who underwent operations for intracranial parasagittal meningiomas. The tumour,
      the sagittal sinus and parasagittal circumflex veins adjacent to the tumour were
      examined. RESULTS: For all 22 patients, the locations and extensions of brain
      surface parasagittal circumflex veins observed from MR brain SAS images
      correlated well with operative findings. Brain surface circumflex veins were
      preserved completely for 17 patients, in four patients tumour-related brain
      surface circumflex veins were resected, and in one patient brain surface
      circumflex veins crossing over the tumour surface were resected. No post
      operative oedema or injury in nervous function was found in these patients, hence
      satisfying surgical outcomes were obtained. CONCLUSION: MR brain SAS is able to
      clearly delineate brain surface circumflex veins which are close to parasagittal
      meningiomas, give an appropriate pre-operative evaluation, and provide
      instructive suggestions for the preservation or resection of veins on the tumour
      surface during the operation. It has great significance in the prevention of
      postoperative vasogenic oedema due to the dysfunction of vein circumfluence and
      the further neuro-dysfunction due to brain oedema. Consequently the surgical
      outcome can be improved and post-operative complications can be reduced.

PMID- 18807594
TI  - Risk factors of morbidity and mortality in patients with perforated peptic ulcer.
AB  - PURPOSE: Peptic ulcer perforation is a serious problem that leads to high
      complication and mortality rates. The aim of this prospective clinical study was
      to evaluate complications and possible risk factors for peri-operative morbidity
      and mortality in patients with perforated peptic ulcer (PPU). MATERIAL AND
      METHODS: Ninety-seven patients hospitalized for PPU at the Department of Surgery,
      Vakif Gureba Training and Research Hospital, between March 1998 and December 2004
      were analysed. RESULTS: The mean age of patients was 38.6 years. Ten patients had
      19 co-morbidities. The mean hospitalisation time was 7.1 days. Twenty-one
      complications in 15 patients occurred. Overall morbidity and mortality rates were
      15.5% and 5.2% respectively. Multivariate logistic regression analysis of 97
      patients revealed that age (p < 0.006) and late admission (p < 0.001) were linked
      to morbidity. The mortality rate tended to be associated with advanced age,
      therapeutic delay and co-morbidities. CONCLUSIONS: Increased patients' age and
      the therapeutic delay, predicted outcome after surgical treatment of PPU.
      Morbidity and mortality could be reduced by avoiding delays in diagnosis and
      treatment, especially in older patients, and by instituting proper treatment of
      any coexisting medical illness.

PMID- 18807595
TI  - Elastic intramedullary nailing of midclavicular fractures.
AB  - The majority of midclavicular fractures are treated conservatively. Fractures
      that require internal fixation are treated by plate osteosynthesis as the
      standard procedure. Elastic stable intramedullary nailing is an increasingly
      popular alternative for the internal fixation of displaced midclavicular
      fractures. In a three-year period, 15 fractures of the clavicle were treated by
      elastic intramedullary nailing. Fracture healing, clinical outcome and
      complications were assessed. Mean follow-up time was one year All fractures
      healed clinically and radiologically. Non-union or infections were not observed.
      Functional results according to the Constant score were excellent. Complications
      consisted of skin irritation in four cases. One acromioclavicular joint
      separation was observed postoperatively. Elastic stable intramedullary nailing of
      displaced midclavicular fractures is a minimally invasive technique with
      excellent functional results and early pain relief.

PMID- 18807596
TI  - Reduction of peritoneal adhesion to polypropylene mesh with the application of
      fibrin glue.
AB  - PURPOSE: The purpose of our study was to evaluate the possibility of the
      reduction of peritoneal adhesions to a polypropylene mesh with fibrin glue.
      METHODS: Forty Wistar rats were assigned to two treatment groups: Group 1)
      hernioplasty with polypropylene mesh plus fibrin glue sealant, and Group 2)
      hernioplasty with polypropylene mesh without fibrin glue sealant. The variables
      evaluated were: presence and density of adhesion, organs or abdominal structures
      adhered to the polypropylene mesh, inflammatory tissular reaction and cell
      recount. RESULTS: Group 1 presented a statistically lower adhesion percentage
      than Group 2 (40% versus 100%, P = 0.0003). The mean areas of mesh patch surfaces
      covered with adhesions were statistically different between Groups 1 and 2 (0.67
      +/- 0.65 cm2 versus 1.60 +/- 0.51 cm2; P = 0.00001). Twelve rats presented with
      adhesions in Group 1; eleven were adhesions to the epiploon and one to the colon.
      In Group 2 there were 16 adhesions to the epiploon, 2 to the colon, 1 to the
      small intestine and 1 to the stomach. Tissular reaction comparison showed a
      significant difference (21 +/- 4.9 versus 17 +/- 4.1; P = 0.006). CONCLUSIONS:
      Fibrin glue sealant significantly reduced the frequency and severity of intra
      abdominal adhesions.

PMID- 18807597
TI  - Jaw claudication as a result of carotid artery disease.
AB  - INTRODUCTION: Jaw claudication is mostly described as a symptom of giant cell
      arteritis. However it can also occur in presence of severe bilateral external
      carotid artery stenosis. REPORT: An 87-year-old man with extensive cardiovascular
      history presented with disabling bilateral jaw claudication. Duplex Scan and MR
      Angiography showed severe bilateral ostial external carotid artery stenosis.
      After unilateral carotid endarterectomy, the symptoms disappeared. DISCUSSION:
      Bilateral jaw claudication as a symptom of carotid atherosclerosis is a rare
      condition. It can be treated by unilateral carotid endarterectomy.

PMID- 18807598
TI  - Endovascular treatment of acute subclavian pseudo-aneurysm after fracture of the
      clavicle.
AB  - Pseudo-aneurysms of the subclavian artery remain a rare complication after
      fracture of the clavicle. Nerve compression has been described with delayed
      paralysis as a consequence. We report a case of delayed diagnosis of a subclavian
      pseudo-aneurysm after a closed fracture of the clavicle in a 93-year-old patient.
      Diagnosis was confirmed by ultrasound and multi-slice-Ct. Two attempts to treat
      the pseudo-aneurysm with percutaneous thrombin injection failed. Considering the
      age of the patient, it was decided to exclude the pseudo-aneurysm by endovascular
      approach. A Hemobahn endoprosthesis was inserted by the introduction of an 11F
      sheath after cutting down the brachial artery under local anaesthesia.
      Angiography revealed complete exclusion of the pseudo-aneurysm. Follow-up at 9
      months by ultrasound confirmed exclusion of the pseudo-aneurysm. Plain X-ray of
      the endograft showed no stent fractures. Paresis of the arm had improved. This
      case illustrates that endovascular exclusion is a safe approach, with reduced
      morbidity, compared with open surgery. Concern about stent deformation and stent
      fractures has been expressed. With the introduction of highly flexible stents,
      one can hope that this complication is less likely to occur. Although follow-up
      is relatively short, we believe that endovascular exclusion of subclavian pseudo
      aneurysms is preferable to a surgical approach.

PMID- 18807599
TI  - Sister Joseph's nodule umbilical manifestation of intraperitoneal carcinomatosis.
AB  - An umbilical metastasis is universally referred to as a sister Joseph's nodule if
      it is caused by extensive intraabdominal neoplastic disease. The presence of an
      umbilical metastasis usually indicates advanced disease, with poor prognosis. We
      report on a 64-year old women with a umbilical nodule that was at first not
      recognised as a metastatic lesion, so the diagnosis and treatment were delayed.
      Knowledge of this eponym can help to avoid delay in diagnosis by alerting the
      clinician and prompting investigations with CT scan and a histological
      examination.

PMID- 18807600
TI  - Goblet cell carcinoid of the appendix: laparoscopic appendectomy or right
      hemicolectomy?
AB  - Goblet cell carcinoids are uncommon tumours with histological features of both
      adenocarcinoma and carcinoid tumour. They occur predominantly in the appendix and
      although the malignant potential remains unclear, adenocarcinoids appear to be
      more aggressive than conventional carcinoids. In this case report, we present a
      goblet cell carcinoid with laparoscopic operative treatment in two stages. A 43
      year-old female patient with constant dullness in the right lower quadrant was
      diagnosed with acute appendicitis and underwent laparoscopic appendectomy.
      Macroscopically, a diffusely inflamed appendix was found with no sign of
      perforation. Histopathological examination revealed a goblet cell carcinoid with
      characteristics of aggressive behaviour, indicating the need for laparoscopic
      right hemicolectomy in which, however, neither residual tumour nor metastatic
      lymph nodes could be found. The postoperative course was uneventful. As they may
      present the same clinical presentation, pathological diagnosis is required to
      distinguish goblet cell carcinoid from acute appendicitis. Two-stage surgery for
      goblet cell carcinoid is advocated in the literature, but the debate still
      continues as to whether the goblet cell carcinoid should be treated by
      appendectomy alone, as for most carcinoids, or by right hemicolectomy, as for the
      appendiceal adenocarcinoma.

PMID- 18807601
TI  - Inflammatory pseudo-tumour of the appendix and acute appendicitis: a case report.
AB  - Inflammatory myofibroblastic tumour (IMT) is a rare benign lesion of unknown
      aetiology. It mimics, clinically and radiologically, malignant tumours
      (especially sarcoma). It was initially described in the lung, but it was
      subsequently recognised that virtually any anatomic location can be involved.
      IMTs of the gastro-intestinal tract are rare and there have been only nine
      confirmed cases involving the appendix to date. We presented a 20-year-old male
      patient with a diagnosis of IMT that caused acute appendicitis. An appendectomy
      is the most efficient treatment in cases where the lesion is limited to the
      appendix. Being aware of such an entity and being careful in the differential
      diagnosis of the appendiceal masses, especially the large masses, may prevent
      overtreatment.

PMID- 18807602
TI  - Extrinsic ileal occlusion secondary to appendiceal mucocele of unusual size.
AB  - Appendiceal mucocele due to papilar cystadenoma is a rare condition,
      characterized by a diffuse swelling, a distension of the lumen secondary to
      accumulation of mucoid substance and occasional mucinous intraperitoneal
      deposits. It is often asymptomatic (approximately 25%) and is found incidentally
      during abdominal imaging studies or surgical exploration. Pre-operative
      recognition is difficult but very important because of the possibility of rupture
      during surgery with the development of pseudomyxoma peritonei. A case of benign
      mucocele presenting acutely as an occlusive syndrome is reported. The surgical
      treatment consisted of an appendicectomy with partial caecectomy. The
      clinicopathological and imaging diagnostic features of this pathological entity,
      as well as the main therapeutic approaches suggested in the literature, are
      commented on.

PMID- 18807603
TI  - Retroperitoneal abscess and extensive subcutaneous emphysema in perforated
      appendicitis: a case report.
AB  - Most of the time, the diagnosis and treatment of appendicitis are
      straightforward. However, a missed diagnosis can sometimes lead to life
      threatening complications. A fatal case of appendicitis in a 76-year-old man who
      presented with progressive abdominal pain, retroperitoneal abscesses and
      extensive subcutaneous emphysema, is described. Eventually, laparotomy showed
      appendicitis perforated into the retroperitoneum without any signs of
      peritonitis. Despite multiple operations the patient died two months after
      admission due to multiple organ failure.

PMID- 18807604
TI  - Perforated caecal volvulus: an unusual complication after anterior resection for
      colorectal carcinoma.
AB  - AIM: To discuss an unusual and rare complication of perforated caecal volvulus
      (CV) following open anterior resection. METHODS: A retrospective review of the
      case notes of a patient. RESULTS: CV is a well known but rare cause of bowel
      obstruction. Chronic constipation, distal colonic obstruction and post-operative
      ileus are potentially aggravating factors for the development of CV in
      anatomically susceptible patients. The anatomical susceptibility for CV was
      noticed during the first operation but prophylactic caecopexy was not performed
      due to lack of evidence in the literature. This patient developed CV after
      anterior resection and subsequently underwent a second laparotmy for right
      hemicolectomy. CONCLUSION: CV is a known but rare case of postoperative bowel
      obstruction. The role of prophylactic caecopexy could be discussed in order to
      avoid the development of postoperative CV in anatomically susceptible patients.

PMID- 18807605
TI  - Solitary splenic metastasis of an adenocarcinoma of the lung 2 years
      postoperatively.
AB  - Metastatic tumours of the spleen are rare and most frequently diagnosed at the
      time of autopsy. Most patients with splenic metastases have widely disseminated
      metastatic disease. We report a case of an asymptomatic, isolated splenic
      metastasis in a 67-year-old man diagnosed 2 years after resection of an
      adenocarcinoma of the lung.

PMID- 18807606
TI  - Spontaneous hepatic rupture during third trimester of pregnancy.
AB  - Hepatic rupture is a rare and devastating complication in pregnancy, mainly
      associated with pre-eclampsia and HELLP (Hemolysis, Elevated Liver enzymes, Low
      Platelet count). It has an incidence of 1 case in 45,000-225,000 births. Nearly
      200 cases have been reported in the international literature. We report a case of
      a hepatic rupture with severe haemorrhage caused by HELLP in a third trimester
      pregnancy. The case was managed successfully with no pathological complications
      for either the mother or the infant. The physician should be aware of this
      condition when dealing with intra-abdominal haemorrhage during pregnancy.

PMID- 18807607
TI  - Unusual manifestation of bronchiolitis obliterans organizing pneumonia.
AB  - Bronchiolitis obliterans organizing pneumonia (BOOP) is an uncommon fibrotic lung
      disease characterized by involvement of the small conducting airways. BOOP has a
      wide spectrum of radiologic and clinical features. Usually, it appears
      radiologically as multiple alveolar patchy areas of consolidation. However,
      different presentations have also been described. We report two cases of solitary
      masses of the lung that preoperatively presented as malignant lesions but were
      subsequently diagnosed as bronchiolitis obliterans organizing pneumonia. One of
      the cases of BOOP was probably secondary to suppuration of a hydatid cyst.
      Complicated hydatid cyst may give rise to various clinical manifestations and may
      present radiologically as a solid lung mass. The radiologic findings of pulmonary
      ruptured or complicated hydatid cyst may resemble primary lung tumor. Open
      surgery can be required for not only for diagnosis but also for treatment of
      solitary BOOP. A review of the literature is also presented.

PMID- 18807608
TI  - Actinomycotic abscess of the anterior abdominal wall: a case report and
      literature review.
AB  - Actinomycosis is a rare, chronic, suppurative, pseudotumoral illness caused by an
      anaerobic gram positive organism usually Actinomyces israelii which can mimick a
      tumoral pathology leading to a mutilating surgical resection. We report a case of
      abdominal actinomycosis and a literature review.

PMID- 18807609
TI  - Anastomotic leakage of a colorectal anastomosis treated by transanal endoscopic
      microsurgery.
AB  - OBJECTIVE: To report a minimal invasive technique for repairing an anastomotic
      leakage with Transanal Endoscopic Microsurgery (T.E.M.) without creating a
      protective ostomy. SUMMARY: There are a large number of techniques for the
      management of anastomotic leakage after colorectal surgery. Depending on the size
      and location of the disruption, a protective ileostomy, a permanent colostomy or
      even reintervention for drainage or closure of the leak may be indicated. In most
      cases the patient faces the morbidity associated with a new intervention, a
      prolonged hospital stay and a future operation for closure of the stoma. In the
      present case a 56-year-old man underwent a laparoscopic rectosigmoid resection
      after two episodes of diverticulitis in six months. An end-to-end circular
      stapled anastomosis was constructed. Unfortunately 8-days postoperatively an
      anastomotic leak occurred. Attempts to close the tear non-surgically with
      colonoscopy and clipping failed. A minimally invasive reintervention with
      transanal endoscopic microsurgery (T.E.M.) was performed without creation of an
      ileostomy. One week postoperatively a gastrografin bowel study showed no leakage.
      To our knowledge, this technique has not yet been reported without the
      simultaneous construction of a stoma. CONCLUSION: We describe a possible
      minimally invasive technique to avoid laparotomy and/or the creation of a
      derivative stoma in the management of anastomotic leakage. Hospital stay is not
      significantly prolonged, future reintervention for closure of stoma is avoided
      and sphincter function is preserved.

PMID- 18807610
TI  - Leonardo da Vinci and Andreas Vesalius; the shoulder girdle and the spine, a
      comparison.
AB  - Leonardo Da Vinci and Andreas Vesalius were two important renaissance persons;
      Vesalius was a surgeon-anatomist who delivered innovative work on the study of
      the human body, Leonardo da Vinci was an artist who delivered strikingly accurate
      and beautiful drawings on the human body. Below we compare both masters with
      regard to their knowledge of the working of the muscles, their method and system
      of dissection and their system and presentation of the drawings. The
      investigation consisted of a comparison between both anatomists, in particular
      concerning their study on the shoulder girdle and spine, by reviewing their
      original work as well as already existing literature on this subject. The
      investigation led to the conclusion that the drawings mentioned meant a change in
      history, and were of high quality, centuries ahead of their time. Both were
      anatomists, both were revolutionary, only one changed history at the moment
      itself, while the other changed history centuries later. Leonardo has made
      beautiful drawings that are at a match with the drawings of today or are even
      better. Vesalius set the start for medicine as a science as it is until this day.
      Their lives differed as strongly as their impact. In the light of their time, the
      achievement they made was extraordinary.

PMID- 18807611
TI  - Concerning: "Day hospital for incisional hernia repair : selection criteria"-
      Donati M. et al. Acta Chir Belg. 2008, 108 : 198-202.

PMID- 18807612
TI  - [Rupture of the ventral serrate muscles (Flying Scapulas) as a symptom of
      muscular dystrophy in Holstein-Friesian heifers on a Dutch dairy farm].
AB  - Within a week of being turned out to pasture, 3 of 30 heifers displayed a symptom
      described in the literature as "Flying Scapulas". The cause of this symptom is
      severe muscular dystrophy, with subsequent rupture of the ventral serrate
      muscles. Blood analysis revealed a deficiency of both vitamin E and selenium in
      all three heifers. No new clinical cases of muscular dystrophy were observed
      after the animals were housed and given vitamin E and selenium supplements. As
      far as is known, this is the first report in which a deficiency of both vitamin E
      and selenium was found in animals with the clinical symptoms of Flying Scapulas.
      This is the first description of Flying Scapulas in cattle in The Netherlands.

PMID- 18807613
TI  - [Arcobacter, a possible new pathogenic bacterium for humans].

PMID- 18807614
TI  - [Whom pays, makes the decision].

PMID- 18807615
TI  - [Q fever: a challenge for the veterinarian].

PMID- 18807617
TI  - [Mammary health indicators UGCN: a good start is half the work!].

PMID- 18807618
TI  - [The veterinary market from an economic perspective].

PMID- 18807619
TI  - [BPW membership counts on the labor market].

PMID- 18807620
TI  - [Veterinary ergonomics: a matter of life style].

PMID- 18807621
TI  - [Instruments, books and other objects memorable to (almost) forgotten opinions,
      therapies, buildings, etc. Blood letting instrument].

PMID- 18807622
TI  - [Que sera].

PMID- 18807623
TI  - [Results of a questionnaire about membership services of KNMVD May 2008].

PMID- 18807624
TI  - Treating prostate cancer, Part II: determining its severity.

PMID- 18807625
TI  - The powerful placebo.

PMID- 18807626
TI  - Pets and your health.

PMID- 18807627
TI  - On call. Every time I walk through a mall or airport, I see machines for reviving
      heart attack victims. My husband has had two heart attacks. He's doing very well
      now, but I wonder if I can get a device like this for our home. And if I get one,
      would I be able to learn how to use it?

PMID- 18807628
TI  - Time for more vitamin D.  Missing out on the "sunshine vitamin" has consequences
      for more than just bone health.

PMID- 18807629
TI  - Heart failure in women.  Heart failure affects increasing numbers of older women,
      but it's becoming easier to prevent and treat.

PMID- 18807630
TI  - Nerve block quells hot flashes in women with breast cancer.

PMID- 18807631
TI  - No cardiovascular help from B vitamins in high-risk women.

PMID- 18807632
TI  - By the way, doctor.  I have small white bumps on my eyelids, which drive me
      crazy.  They don't hurt, but they look awful.  I've been told they're Meibomian
      cysts and that the only solution is surgery.  What is your take on this?

PMID- 18807633
TI  - What was masculine about the public sphere? Gender and the coffeehouse milieu in
      post-restoration England.

PMID- 18807635
TI  - [On the use of ololiuqui in colonial Mexico].

PMID- 18807636
TI  - "For how can they be guilty?" Lesbian and bisexual women in Manley's New
      Atlantis.

PMID- 18807638
TI  - Suicide and the secularization of the body in early modern Saxony.

PMID- 18807639
TI  - [The spells of Don Marcos Humuta: order and conflict in an Opata community of
      Sonora: Bacerac, 1704].

PMID- 18807641
TI  - The role of Quaker women in the seventeenth century, and the experiences of the
      Wiltshire friends.

PMID- 18807642
TI  - [The so-called poor in Seville under Charles II].

PMID- 18807643
TI  - Retraction Notice: Clinical Strategies for Preventing Postoperative Nausea and
      Vomitting after Middle Ear Surgery in Adult Patients
AB  - Formal retraction notice of article entitled Clinical Strategies for Preventing
      Postoperative Nausea and Vomitting after Middle Ear Surgery in Adult Patients
      (Curr Drug Saf. 2011 Apr;6(2):122-7) by Dr Y. Fujii. This article is being
      retracted as a result of:Failure of Dr. Fijii's institution as well as of himself
      to rationalize the legitimacy of the study and/or its data as stipulated in
      request by the Editors-in-Chief of the journals extended on April 9, 2012.

PMID- 18807644
TI  - [Village farms and smallholdings in Northern Livonia in the 17th century].

PMID- 18807645
TI  - The Medicaid undercount: real or perceived bias in estimates of coverage in
      general population surveys?

PMID- 18807646
TI  - Improving access to improve quality: evaluation of an organizational innovation.

PMID- 18807647
TI  - Surviving the perfect storm: impacts of benefit reductions and increased cost
      sharing in a Medicaid program.

PMID- 18807648
TI  - The continuing cost of privatization: extra payments to Medicare Advantage plans
      in 2008.
AB  - The Medicare Modernization Act of 2003 explicitly increased Medicare payments to
      private Medicare Advantage (MA) plans. As a result, every MA plan in the nation
      is paid more for its enrollees than they would have been expected to cost in
      traditional fee-for-service Medicare. The authors calculate that payments to MA
      plans in 2008 will be 12.4 percent greater than the corresponding costs in
      traditional Medicare-an average increase of $986 per MA plan enrollee, for a
      total of more than $8.5 billion. Over the five-year period 2004-2008, extra
      payments to MA plans are estimated to have totaled nearly $33 billion. Although
      Congress recently enacted modest reductions in MA plan payments, these changes
      will not take effect until 2010. Moreover, while the new legislation removes a
      few factors contributing to the extra payments, a number of other factors remain
      unaffected.

PMID- 18807649
TI  - [Phenemal and alcoholic ketoacidosis].

PMID- 18807650
TI  - [Prostatic Cancer Patient Association PROPA--and information about prostatic
      cancer].

PMID- 18807651
TI  - Maternal-fetal medicine.

PMID- 18807652
TI  - Internal medicine.

PMID- 18807653
TI  - Retraction statement. Effect of inhalational anesthetics on cytotoxicity and
      intracellular calcium differently in rat pheochromocytoma cells (PC12).

PMID- 18807654
TI  - [HYVET study - treatment for hypertension].

PMID- 18807655
TI  - [Development and future of medical research in Poland].

PMID- 18807656
TI  - [About PEITHO, idols, suggestions and temptations - or how to treat submassive
      pulmonary embolism].

PMID- 18807657
TI  - [Introduction to cognitive behavior therapy].

PMID- 18807659
TI  - [Cognitive behavior therapy: cognitive reconstruction].

PMID- 18807658
TI  - [Respiration control and psychological patient education for patients with panic
      disorder].

PMID- 18807660
TI  - [Cognitive behavior therapy of gradual exposure for agoraphobic stimulation].

PMID- 18807661
TI  - [Early diagnosis of and therapy for mental disorders].

PMID- 18807662
TI  - The management of the trauma patient with medically-altered coagulation.

PMID- 18807663
TI  - The general surgery residency at Ochsner Clinic Foundation: training the
      'surgeon's surgeon'.
AB  - The general surgery residency at Ochsner is, to some extent, a hybrid, combining
      the amenities and resources of an excellent private hospital/clinic with the
      academic tone of a university program. Our primary mission is to educate and
      train outstanding young surgeons who are ready to either enter clinical practice
      or undertake advanced fellowship training. Although our mission is not primarily
      to train full-time academic surgeons, our alumni include a number of
      distinguished academic surgeons. The passage from medical student to accomplished
      surgeon is exciting, and the camaraderie that a surgical resident establishes
      with his/her peers and faculty lasts for a lifetime. As surgical educators, we
      are privileged to spend a major part of our lives with a talented, bright and
      passionate group of young physicians who have set their sights on entering what I
      believe to be the world's greatest profession: general surgery.

PMID- 18807664
TI  - Blunt liver injury in children and adults: is there really a difference?
AB  - Hepatic injuries are increasingly managed nonoperatively with the availability of
      adjunctive procedures such as angiography, ERCP, and percutaneous drainage.
      Although extensively discussed in the adult population, little has been reported
      on outcomes and management of pediatric liver injury. Retrospective review of all
      patients with blunt liver injuries admitted to an adult Level I trauma center and
      pediatric trauma center within the same community was performed from 2004 to
      2006. The necessity for operation, adjuncts to nonoperative management, and
      outcome were collected and compared for the pediatric (PED) (<18 years of age)
      versus the adult (> or = 18 years of age) injured patients. There were 389 liver
      injuries identified (PED = 90, adult = 299); 25 per cent of adult injuries were
      greater than or equal to grade III, while 23 per cent of PED injuries were high
      grade injuries. Each group of patients had similar rates of primary operative
      intervention: adult patients (18%) versus PED patients (16%). Adjunctive
      therapies were rarely used in the PED patients with only one patient requiring a
      percutaneous drain and one patient undergoing ERCP twice. Conversely, the adult
      patient group required eight percutaneous drains, 15 angiograms, 6 ERCPs and 14
      laparoscopic abdominal washout procedures. ICU and hospital LOS were 25 per cent
      and 33 per cent lower in the adult population for high-grade injuries. The
      overall mortality rates were similar at 7 per cent (PED) and 9 per cent (adult).
      Liver-related mortality was 50 per cent (3/6 deaths) in the PED group with no
      liver-related deaths in the adult group (27 deaths). Adult patients with blunt
      liver injury were no more likely to sustain high grade liver injuries than PED
      patients. Furthermore, adult and PED patients underwent similar rates of
      operative intervention and primary liver procedures. Adult patients used
      adjunctive measures as part of their nonoperative management more frequently, but
      both subsets had similar length of hospital stays and low overall mortality. A
      higher rate of liver-related mortality was seen in the PED population. Overall,
      PED patients seemed to sustain fewer liver related complications necessitating
      invasive procedures despite similar injury patterns.

PMID- 18807665
TI  - Anticoagulation and the elderly head trauma patient.
AB  - We sought to determine the effect of anticoagulation therapy on outcomes in
      elderly patients with closed head injury. We retrospectively reviewed elderly
      closed head injury patients (> or = 65 years) comparing 52 patients on warfarin
      (AC) with 439 patients not on warfarin (NAC) with subsequent 1:3 propensity
      matching used to analyze comparable groups. The overall AC group had a higher
      head abbreviated injury score (AIS) (4.0 +/- 0.7 vs 3.8 +/- 0.7, P = 0.04)
      compared with the NAC group. After propensity matching, 49 AC patients were
      compared with 147 NAC patients who were similar for age, gender, injury severity
      score, and head AIS. Admission INR was higher in the AC group compared to the NAC
      group (2.5 +/- 1.3 vs 1.1 +/- 0.3, P < 0.0001) and the AC group had a higher
      mortality rate (38.8% AC (19/49) vs 23.1% NAC (34/147), P = 0.04). In the AC
      group, survivors and nonsurvivors had similar repeat International Normalized
      Ratio (INR) values (1.57 +/- 0.65 survivors vs 1.8 +/- 0.72 nonsurvivors, P =
      0.31). The AC group experienced greater morbidity after trauma and had higher
      mortality rates than their NAC counterparts. Prevention of injury and more
      selective use of warfarin in this patient population are essential to decrease
      mortality.

PMID- 18807666
TI  - Measuring intra-abdominal pressure outside the ICU: validation of a simple
      bedside method.
AB  - Intra-abdominal pressure measurement is essential to the diagnosis of patients
      with intraabdominal hypertension or abdominal compartment syndrome. The most
      common method for measuring intra-abdominal pressure (IAP) is the intravesicular
      or "bladder" technique, which requires electronic monitoring technology not
      available on the typical surgical ward. Herein we describe and validate a simple,
      rapid screening method for bedside IAP measurement using the patient's indwelling
      urinary catheter and a readily available intravenous tubing extension. Validation
      of this technique across the clinically important IAP diagnostic spectrum
      demonstrated acceptable bias (1.6 mm Hg; 95% confidence interval 1.4-1.8) with
      limits of agreement of 0.36 to 2.8. This demonstrates good agreement between the
      two IAP methods and validates the bedside technique as a simple, cost-effective,
      and reproducible method for screening IAP measurements outside of the critical
      care setting.

PMID- 18807667
TI  - Necrotizing fasciitis with no mortality or limb loss.
AB  - Necrotizing fasciitis is a potentially lethal invasive soft tissue infection.
      Early aggressive antibiotic therapy and surgical debridement have been the
      hallmark of successful therapy. It is commonly held that delays in surgical
      debridement significantly increase the mortality rate and rate of limb loss. A
      mortality rate of 20 per cent or greater has been reported throughout the last 80
      years. We recently reviewed the cases of 20 consecutive patients admitted to our
      hospital in various stages of necrotizing fasciitis progression. Treatment of all
      20 patients consisted of antibiotic therapy and surgical debridement, with
      frequent follow-up serial debridement. Topical negative pressure was achieved
      with the use of the Vacuum Assisted Closure system. An aggressive surgical
      approach, (including the frequency of debridement, appropriate antibiotic
      utilization, and use of the Vacuum Assisted Closure system), significantly
      impacted our results, despite delays in treatment and progression of the
      infection.

PMID- 18807668
TI  - Papillary endothelial hyperplasia of the adrenal gland: report of a case and
      review of the literature.
AB  - Papillary endothelial hyperplasia (PEH) is a benign vascular proliferative
      process most frequently seen in the skin and integument, but may involve any of
      the visceral organs. It is a rare entity, with less than 30 cases of visceral PEH
      described in the literature. Adrenal papillary endothelial hyperplasia is an
      exceedingly rare process and is the basis of this review. A 66-year-old female
      was referred for evaluation of an asymptomatic 6 cm right adrenal mass. Computed
      tomography indicated that the lesion was solid and hypervascular. After
      appropriate workup, the patient underwent laparoscopic adrenalectomy. The
      pathologic analysis was consistent with adrenal PEH. The patient recovered
      without incident and is doing well at 1 year follow-up. A review of the world's
      literature on papillary endothelial hyperplasia (PEH), and in particular adrenal
      PEH, yields five previous reports of this entity, and no comprehensive review. A
      compilation of the now six patients with adrenal PEH reveals several common
      features: five of six patients were female and mean age was 64 years. The disease
      radiologically mimics adrenal cortical carcinoma mandating a surgical oncological
      technique. Pathologic differentiation from angiosarcoma can be a difficult task
      requiring evaluation by an experienced pathologist.

PMID- 18807669
TI  - Implementation of a preoperative briefing protocol improves accuracy of teamwork
      assessment in the operating room.
AB  - This study examined the effect of implementing a new preoperative briefing
      protocol on self- and peer-assessments of individual operating room (OR) teamwork
      behaviors. From July 2006 to February 2007, OR teamwork performance at a rural
      community hospital was evaluated before and after training and implementation of
      the protocol. After each case, every member on the team completed a 360-degree
      type teamwork behavior evaluation containing both self- and peer-assessments
      using a six-point Likert type scale (1 = definitely no to 6 = definitely yes).
      Individual behavior change was measured using the mean scale score of pre and
      postprotocol assessments. Statistical analysis included t test for both pre/post
      and self/peer differences. Data were available for one general surgeon and nine
      OR staff (pre = 20 cases, post = 16 cases). The preprotocol self-assessment mean
      score was significantly higher than peer-assessment (5.63 vs 5.29, P < 0.0267).
      Pre and postprotocol peer assessment mean scores revealed a statistically
      significant gain in teamwork behaviors. No difference was observed in
      postassessment mean scores for self- and peer-assessments. Individuals
      overestimated their teamwork behaviors before protocol implementation. Using a
      preoperative protocol seems to improve OR staff teamwork behaviors and self
      assessment accuracy. The use of a 360-degree assessment method targeting
      specific, observable behaviors may be useful in evaluating team-based
      interventions and enhancing teamwork effectiveness.

PMID- 18807670
TI  - Intra-abdominal lesions could be missed by inadequate laparoscopy.
AB  - Laparoscopic resection has become one of the choices for colectomy for various
      colon and rectal diseases in recent years. Despite some uncertainties of
      laparoscopic procedures, especially during cancer surgery, its popularity has
      forced surgeons to pursue the approach. One of the concerns is inadequate
      examination of the intra-abdominal organs with a laparoscope. This study is a
      retrospective analysis of a single surgeon's experience of the frequencies of
      unexpected findings during laparotomies. From July 1990 to November 2005, 2775
      patients with various colorectal diseases receiving laparotomies by a single
      surgeon were analyzed. Among them, 2282 patients were operated for primary
      colorectal cancer. Excluded were patients who did not receive a formal
      laparotomy, who had a recent laparotomy, who had peritoneal and omental
      metastasis, and whose pathology did not attract attention for management.
      Exploration of the entire peritoneal cavity was performed for all cases in the
      series. There were 1423 males and 1352 females. Ages ranged from 12 to 94 years,
      averaging 62.6-years-old. Forty-six patients (1.7%) were found to have unexpected
      intra-abdominal lesions during laparotomies. Eleven patients were found to have
      synchronous colorectal cancers; five patients were found to have unexpected liver
      metastases; three patients each were found to have gastric cancers, stromal
      tumors of the small bowel, and ectopic pancreas; two patients each were found to
      have gastric leiomyosarcomas, pancreatic cancers, mucoceles of the appendix,
      ulcers of the small intestine, bleeding Meckel's diverticula, pancreatitis, and
      perforations of the ileum; one patient each was found to have gall bladder
      cancer, malignant carcinoid tumor, pheochromocytoma, diverticulitis of the
      jejunum, diverticulitis of the colon, duplication of the colon, and aortic
      aneurysm larger than 6 cm. Forty-one of the lesions were likely to be missed by
      laparoscope. This experience suggests that incomplete laparotomies might miss
      various pathologies. Laparoscopy is not a complete form of laparotomy because of
      loss of tactile sensation. Laparoscopy might result in an inadequate or
      inappropriate management due to misdiagnosis.

PMID- 18807671
TI  - Endoscopy-assisted laparoscopic resection of gastric heterotopic pancreas.
AB  - This is a case report of a 51-year-old white female who underwent an endoscopy
      assisted laparoscopic resection of a submucosal mass in the prepyloric region of
      the stomach, which turned out to be heterotopic pancreas. She presented with
      vague upper gastrointestinal complaints of pain, early satiety, nausea, vomiting,
      and an 8 pound weight loss. Her only diagnostic workup was an upper endoscopy,
      which revealed this submucosal umbilicated mass. This manuscript provides a
      detailed description of the operation and a discussion and review of the
      literature about gastric heterotopic pancreas.

PMID- 18807672
TI  - Role of ultrasound screening for gallbladder disease in pretransplant patients.
AB  - There is no uniform data regarding prophylactic cholecystectomy in patients
      undergoing renal transplantation with gallbladder disease. Data analyses suggest
      that posttransplant patients on cyclosporine have a higher incidence of
      gallbladder calcifications compared with nonimmunosuppressed patients.
      Laparoscopic cholecystectomy is a relatively safe procedure in modern-day
      surgery. Taking these facts into consideration, we attempted to compare risks and
      complications associated with gallbladder disease and eventual cholecystectomy in
      pretransplant versus posttransplant patients. Between June 1999 and December
      2005, 210 renal transplants were performed at our institution. One hundred four
      patients who had transplants before April 2003 were not screened for gallbladder
      disease and nine of these patients developed gallbladder disease. These patients
      form our control group. One hundred six patients who had transplants after April
      2003 had pretransplant screening for gallbladder disease and 11 patients were
      identified with gallbladder disease. These patients form our study group. Nine
      patients who developed gallbladder disease after renal transplant underwent
      laparoscopic cholecystectomy with three resulting morbidities (33%), two graft
      losses (22%), and one mortality (11%). There was one mortality (11%) in this
      group. One patient in the study group died of acute gallstone pancreatitis. Of
      the 11 patients who were found to have gallbladder disease on screening, nine
      patients underwent laparoscopic cholecystectomy with one morbidity and no
      mortality or graft loss. Given the relative rarity of the critical events in this
      study (morbidity, mortality, and graft loss), the definitive statistical value of
      prescreening for gallbladder disease cannot be established. However, our results
      are suggestive of clinical value and thus we tentatively recommend ultrasound
      screening for gallbladder disease for all pretransplant patients and laparoscopic
      cholecystectomy for those identified to have gallbladder disease.

PMID- 18807673
TI  - Prevalence of sleep apnea in morbidly obese patients who presented for weight
      loss surgery evaluation: more evidence for routine screening for obstructive
      sleep apnea before weight loss surgery.
AB  - The incidence of obstructive sleep apnea has been underestimated in morbidly
      obese patients who present for evaluation for weight loss surgery. This
      retrospective study shows that the incidence of obstructive sleep apnea in this
      patient population is greater than 70 per cent and increases in incidence as the
      body mass index increases. Obstructive sleep apnea (OSA) is a common comorbidity
      in obese patients who present for evaluation for gastric bypass surgery. The
      incidence of sleep apnea in obese patients has been reported to be as high as 40
      per cent. A retrospective review of our prospectively collected database was
      performed. All patients being evaluated for weight loss surgery for obesity were
      screened preoperatively for OSA using a sleep study. The overall incidence of
      sleep apnea in our patients was 78 per cent (227 of 290). All 227 were diagnosed
      by formal sleep study. There were 63 (22%) males and 227 (78%) females. The mean
      age was 43 years (range, 17-75 years). The mean body mass index (BMI) was 52
      kg/m2 (range, 31-94 kg/m2). The prevalence of OSA in the severely obese group
      (BMI 35-39.9 kg/m2) was 71 per cent. For the morbidly obese group (BMI 40-40.9
      kg/m2), the prevalence was 74 per cent and for the superobese group (BMI 50-59.9
      kg/m2) 77 per cent. Those with a BMI 60 kg/m2 or greater, the prevalence of OSA
      rose to 95 per cent. The incidence of sleep apnea in patients presenting for
      weight loss surgery was greater than 70 per cent in our study. Patients
      presenting for weight loss surgery should undergo a formal sleep study to
      diagnose OSA before bariatric surgery.

PMID- 18807674
TI  - The influence of diabetes mellitus in patients undergoing coronary artery bypass
      graft surgery: a prospective cohort study.
AB  - This study was conducted to prospectively assess if there are any outcome
      differences between patients undergoing coronary artery bypass graft surgery with
      and without diabetes. This is an 11-year, prospective, hospitalization cohort
      study. Data were collected on 225 variables. A total of 8935 patients were
      available for our analysis (6023 nondiabetics, 319 diet-controlled diabetics,
      1636 diabetics on oral medications, 957 insulin-controlled diabetics). Compared
      with nondiabetics, diet-treated diabetics possessed four significant
      comorbidities, diabetics treated with oral medications possessed 12 significant
      comorbidities, and insulin-treated diabetics possessed 13 significant
      comorbidities (P < 0.05). There was no significant difference between diet
      treated diabetics and nondiabetics for all outcomes. Diabetics treated with oral
      medications possessed a longer length of stay [relative risk (RR), 1.09; CI, 1.08
      1.10], longer intensive care unit length of stay (RR, 1.56; CI, 1.12-2.00), and
      more intraoperative complications (RR, 1.42; CI, 1.12-1.66). Insulin-treated
      diabetics possessed more neurological complications (RR, 2.39; CI, 1.52-3.77),
      wound complications (RR, 2.42; CI, 1.19-4.95), and renal complications (RR, 2.43;
      CI, 1.70-3.49), longer length of stay (RR, 1.20; CI, 1.14-1.27), and longer
      intensive care unit length of stay (RR, 1.33; CI, 1.16-1.48). In diabetics
      undergoing coronary artery bypass graft surgery, as their diabetes progresses
      from diet treated with oral medications to insulin-dependent, this is associated
      with more comorbidities at surgical presentation and more morbidity after
      surgery.

PMID- 18807675
TI  - Insulin requirements in the intensive care unit in response to infection.
AB  - Infectious complications in the intensive care unit (ICU) are classically
      identified when an elevated temperature triggers obtaining cultures. Elevated
      temperature, however, is a nonspecific marker of infection and may occur well
      into the course of the infection. The goal of this study was to evaluate whether
      escalating insulin demands may serve as an earlier marker for infection. A
      retrospective review of a prospective database from a trauma ICU over a 6-month
      period was done for all patients who developed infection while in the ICU. All
      patients in the ICU are placed at admission on an intensive insulin protocol with
      target blood glucose levels between 80 and 110 mg/dL. Data were collected on
      infection, insulin needs, blood glucose levels, temperature, white blood cell
      count, and antibiotic use. Twenty-four infections were identified, with 16
      pneumonias, four bloodstream infections, and four urinary tract infections.
      Twelve of the 24 patients had increasing insulin needs in the 3 days preceding
      their infection diagnosis, with nine of the 12 requiring continued escalation of
      insulin needs from preinfection Day 3 to 2 to 1 (D3, D2, D1). In five of the 12
      patients, the escalation of insulin dose preceded the elevated temperature, and
      in three of the 12 patients, the escalation preceded elevation of the white blood
      cell count above 12. For all 24 patients, the average insulin dose increased
      steadily, from 1.8 U/hr on D3 preinfection to 2.5 U/hr D2 and 3.1 U/hr D1.
      Infection does seem to be preceded by escalating insulin demands in many
      patients. A prospective study to evaluate the value of increased insulin demand
      as a marker for developing infection is warranted.

PMID- 18807676
TI  - Acquired jejunoileal diverticulosis and its complications: a review of the
      literature.
AB  - Jejunoileal diverticulosis is a rare entity. Jejunoileal diverticulosis is not a
      disease that surgeons see often in clinical practice; however, it should remain
      on the differential diagnosis for any patient with an acute abdomen or
      gastrointestinal bleeding of unknown origin. It can present with a wide range of
      clinical scenarios and when patients experience chronic symptoms such as
      bloating, abdominal pain, nausea, bacterial overgrowth, or malabsorption, medical
      therapy is successful in most patients. However, when patients present with acute
      symptoms of bleeding, inflammation, perforation, or obstruction, surgical
      resection and primary anastomosis is often the treatment of choice. If patients
      are asymptomatic, they are better left alone, even when discovered incidentally
      in the operating room. In closing, the possibility of a patient having jejunal
      diverticular disease should be suspected whenever the symptoms of obscure
      abdominal pain, anemia, dilated jejunal loops on abdominal radiographs, a history
      of colonic diverticuli, and a history of acute appendicitis.

PMID- 18807677
TI  - A comparison of flexion and extension radiographs with computed tomography of the
      cervical spine in blunt trauma.
AB  - The purpose of this study was to compare flexion and extension (F/E) cervical
      radiographs with CT of the cervical spine in patients sustaining blunt trauma for
      the evaluation of ligamentous injury. A retrospective chart review of 2 years
      duration at an American College of Surgeons-verified Level I trauma center was
      performed. All patients sustaining blunt trauma who were evaluated with both a CT
      as well as F/E radiographs were identified. Exclusion criteria included
      penetrating injuries, neurologic symptoms, and age younger than 18 years. Follow
      up MRI of each positive F/E radiograph after a negative CT scan was performed.
      Flexion and extension cervical radiographs were obtained in 379 patients after
      CT. Eight positive F/E radiographs were obtained after a negative CT scan. Follow
      up MRI was negative for ligamentous injury in all cases. No cases of a clinically
      relevant positive F/E radiograph after a negative CT scan were identified. Follow
      up F/E radiographs are not efficacious when a negative CT has been performed in
      blunt trauma without neurologic findings.

PMID- 18807678
TI  - A protocol for the rapid normalization of INR in trauma patients with
      intracranial hemorrhage on prescribed warfarin therapy.
AB  - Trauma patients on prescribed warfarin therapy sustaining intracranial hemorrhage
      can be difficult to manage. Rapid normalization of coagulopathy is imperative to
      operative intervention and may affect outcomes. To identify and expedite warfarin
      reversal, we designed a protocol to administer a prothrombin complex concentrate.
      A Proplex T protocol was instituted in May 2004. It dictated that trauma patients
      with an International Normalized Ratio (INR) greater than 1.5, history of
      prescribed warfarin therapy, and intracranial hemorrhage on CT scan receive a
      prothrombin complex concentrate for reversal of their coagulopathy. Neither the
      protocol nor the factor concentrate was validated for use in this subset of
      trauma patients; therefore, adherence to the protocol and use of the factor
      concentrate was not mandatory. Patients not administered the prothrombin complex
      concentrate received vitamin K and fresh-frozen plasma. The protocol resulted in
      an increased number of patients receiving Proplex T (54.3% vs 35.4%, P = 0.047).
      Protocol patients had improved times to normalization of INR (331.3 vs 737.8
      minutes, P = 0.048), number of patients with reversal of coagulopathy (73.2% vs
      50.9%, P = 0.026), and time to operative intervention (222.6 vs 351.3 minutes, P
      = 0.045) compared with control subjects. There were no differences in intensive
      care unit (ICU) days, hospital days, or mortality. The Proplex T protocol
      increased the number of patients who received prothrombin complex concentrate,
      provided rapid normalization of INR, and improved time to operative intervention.

PMID- 18807679
TI  - Taser and Taser associated injuries: a case series.
AB  - Taser devices were introduced in 1974 and are increasingly used by law
      enforcement agencies. Taser use theoretically reduces the risk of injury and
      death by decreasing the use of lethal force. We report a spectrum of injuries
      sustained by four patients subdued with Taser devices. Injuries identified in our
      review included: 1) a basilar skull fracture, right subarachnoid hemorrhage, and
      left-sided epidural hemorrhage necessitating craniotomy; 2) a concussion, facial
      laceration, comminuted nasal fracture, and orbital floor fracture; 3) penetration
      of the outer table and cortex of the cranium by a Taser probe with seizure-like
      activity reported by the officer when the Taser was activated; and 4) a forehead
      hematoma and laceration. The Taser operator's manual states that these devices
      are designed to incapacitate a target from a safe distance without causing death
      or permanent injury. However, individuals may be exposed to the potential for
      significant injury. These devices represent a new mechanism for potential injury.
      Trauma surgeons and law enforcement agencies should be aware of the potential
      danger of significant head injuries as a result of loss of neuromuscular control.

PMID- 18807680
TI  - How we die: the impact of nonneurologic organ dysfunction after severe traumatic
      brain injury.
AB  - Although nonneurologic organ dysfunction (NNOD) has been shown to significantly
      affect mortality in subarachnoid hemorrhage, the contribution of NNOD to
      mortality after severe traumatic brain injury (TBI) has yet to be defined. We
      hypothesized that NNOD has a significant impact on mortality after severe TBI.
      The trauma registry was queried for all patients admitted between January 2004
      and December 2004 who died during their initial hospitalization after severe TBI
      (head Abbreviated Injury Score 3 or greater). Cause of death and contributing
      factors to mortality were determined by an attending trauma surgeon from the
      medical record. The data were analyzed using both Fisher's exact and Wilcoxon
      rank sum. One hundred thirty-five patients met inclusion criteria. Sixty-seven
      per cent were males, 83 per cent were white, and the mean age was 38.5 years.
      Mean length of stay was 2.9 days. Fifty-four patients (40%) had isolated TBI
      (chest Abbreviated Injury Score = 0, abdominal Abbreviated Injury Score = 0). Of
      the 81 deaths attributed to a single cause, 48 (60%) patients died from
      nonsurvivable TBI or brain death, whereas 33 (40%) died of a nonneurologic cause.
      Cardiovascular and respiratory dysfunction (excluding pneumonia) contributed to
      mortality in 51.1 per cent and 34.1 per cent of patients, respectively. NNOD
      contributes to approximately two-thirds of all deaths after severe TBI. These
      complications occur early and are seen even among those with isolated head
      injuries. These findings demonstrate the impact of the extracranial
      manifestations of severe TBI on overall mortality and highlight potential areas
      for future intervention and research.

PMID- 18807681
TI  - Primary extramedullary plasmacytomas of the colon.

PMID- 18807682
TI  - Supernumerary kidney in a term infant with VATER association.

PMID- 18807683
TI  - Serial hemoglobin levels play no significant role in the decision-making process
      of nonoperative management of blunt splenic trauma.

PMID- 18807684
TI  - "July Effect": an evaluation of a level I teaching hospital's trauma service
      seasonal mortality rates.

PMID- 18807685
TI  - Synchronous medullary and follicular carcinomas of the thyroid: a case report.

PMID- 18807686
TI  - Acute acalculous cholecystitis in a pediatric trauma patient.

PMID- 18807687
TI  - Preperitoneal Richter's hernia after laparoscopic gastric bypass: management with
      a laparoscopic approach.

PMID- 18807688
TI  - Fetus in fetu presenting as an abdominal mass in a newborn female infant.

PMID- 18807690
TI  - Paul Revere revisited: the British (P4Ps) are coming!

PMID- 18807689
TI  - Trail of tiers.

PMID- 18807691
TI  - The facts on insurance company ratings of physicians.

PMID- 18807692
TI  - Providing interpreters for a patient's companion.

PMID- 18807693
TI  - Insurance rating & tiering: the TMA fights for a fair system for physicians.

PMID- 18807694
TI  - Drastic measures in Massachusetts.

PMID- 18807695
TI  - Reports in the record--what is your protocol?

PMID- 18807696
TI  - PHI authorizations required By HIPAA.

PMID- 18807697
TI  - A shot in the arm for e-prescribing.

PMID- 18807698
TI  - PQRI and the MD: an assessment of physician attitudes toward and reporting ease
      of the Physician Quality Reporting Initiative.

PMID- 18807699
TI  - Civil rights: physicians who treat prisoners.

PMID- 18807700
TI  - [Polyneuropathy--differential diagnosis and etiology].

PMID- 18807701
TI  - [Septic arthritis? Gonococcal infection despite negative bacterial cultures].
AB  - Clinical signs of acute arthritis are non-specific. An acute painfull joint with
      effusion of unknown origin needs to be evaluated by puncture. The analysis of the
      synovial fluid will enable to divide an arthritis into three categories: crystal
      induced, rheumatological or septic arthritis. A bacterial infection should always
      be suspected. Cultures from blood, synovia and Gram stain do not reliably exclude
      a bacterial infection. If gonococcal, mycobacterial, borrelial and non-gonococcal
      infective arthritis under antibiotic therapy is suspected, direct DNA
      amplification can be helpful. A disseminated gonococcal infection (DGI) must be
      suspected on appearance of tenosynovitis, polyarthralgia and skin lesions. The
      clinical picture, diagnosis and therapy of a case with DGI is discussed.

PMID- 18807702
TI  - ["Be your own risk-manager!"--the discourse on risk in German HIV/AIDS
      prevention].
AB  - This article presents, some results of a discourse analysis on the HIV/AIDS
      Prevention in Germany. The Analysis has been carried out for a thesis in
      historical anthropology and focuses on the dicourse on risk, which becomes
      evident in the statements related to HIV/AIDS-Prevention. First of all, the
      article shows, how the description of risky situations replaces the construction
      of high-risk groups. Moreover, the article retraces changes in the strategies of
      HIV/AIDS-Prevention over the last 25 years and pays special attention to
      references to risky situations.

PMID- 18807703
TI  - [Drug therapy in the elderly. Excerpts].

PMID- 18807704
TI  - [Scepticism is warranted or when the CT scan reveals to be a pitfall].
AB  - We report the case of a 72-year old woman with known metastatic breast cancer who
      presented to the emergency department with progressive dyspnea on exertion and
      chest pain. The diagnosis of pulmonary embolism could be established by pulmonary
      scintigraphy after computed tomography and ultrasound of the lower extremities
      had been negative in spite of a moderate clinical pretest probability (Wells
      score). This case shows that even if we manage suspected pulmonary embolism using
      algorithms combining clinical probability, computed tomography and ultrasound we
      must remain aware of eventually missing the diagnosis and carry on investigating
      cases with elevated clinical probability.

PMID- 18807705
TI  - Oncology nurses are key to ensuring that patients' decision making is truly
      informed.

PMID- 18807706
TI  - Advances in prostate cancer treatment.

PMID- 18807707
TI  - What advancements have you seen in prostate cancer treatment?

PMID- 18807708
TI  - Special patients touch the lives of oncology nurses.

PMID- 18807709
TI  - Manage infusion reactions from cetuximab.

PMID- 18807711
TI  - Strengthen your verbal and nonverbal communication.

PMID- 18807710
TI  - Practice the art of listening.

PMID- 18807712
TI  - Vitamin D and cancer: more questions than answers remain.

PMID- 18807713
TI  - Oropharyngeal cancer in men associated with HPV.

PMID- 18807714
TI  - [Observation on the central afferent pathway of "Guanyuan" (CV 4) under normal
      and pathological states and the influence of electroacupuncture].
AB  - OBJECTIVE: To investigate the afferent pathways of "Guanyuan" (CV 4) under normal
      and pathological states and to observe the effect of electroacupuncture (EA) on
      them. METHODS: Twenty-four female SD rats were randomly divided into normal
      control (NC), NC + EA, ovariectomy (OVX) and OVX + EA groups, with 6 cases in
      each. Four weeks after OVX, Pseudorabies Virus (PRV, 10 microl liquid containing
      10(8) plaque-forming units) was injected into CV4. Thirty minutes after PRV
      injection, EA (2 Hz, 2-3 mA) was applied to CV4 for 30 minutes, once daily for 3
      days. Six hours after the third EA treatment, all the rats were perfused
      transcardially with 4% paraformaldehyde under anesthesia, followed by sampling
      the brain and spinal cord and cutting into sections (35 microm).
      Immunohistochemical method (rabbit anti-rat beta-galactosidase) was used to
      display PRV immunoreactive (PRV-IR) positive neurons. RESULTS: 1) After injection
      of PRV, PRV-IR positive cells widely distributed in the spinal cord (cervical,
      thoracic and lumbar segments), brain stem (nucleus of solitary tract, cuneate
      nucleus, gigantocellular reticular nucleus, nucleus of spinal tract of trigeminal
      nerve, nucleus raphe magnus, locus caeruleus, etc), hypothalamus and cerebral
      cortex in each group. 2) After OVX, apparently fewer PRV-IR positive cells were
      found in some nuclei as medial septum nucleus (MSN), arcuate nucleus (ARC),
      diagonal band nucleus (DBN), paraventricular nucleus (PVN) which have close
      relation with endocrine activity (P<0.05); and rarely seen in ventromedial
      hypothalamus (VMH) and lateral preoptic area (LPO) (P<0.01). But in OVX + EA
      group, PRV-IR positive cells in above regions or nuclei increased significantly
      (P<0.05 or P<0.01). No obvious difference was found between NC and NC+ EA groups
      in the number of PRV-IR positive cells (P>0.05). CONCLUSION: Following OVX, PRV
      IR positive cells in neuroendocrine-related nuclei of hypothalamus reduced
      significantly in number; EA of "Guanyuan" (CV 4) can promote the recovery of
      these neurons in above mentioned nuclei.

PMID- 18807715
TI  - [Effect of high-frequency electroacupuncture on lipid metabolism in obesity
      rats].
AB  - OBJECTIVE: To observe the effect of high-frequency electroacupuncture (EA) on
      lipid metabolism in obesity rats. METHODS: Fifty-one SD rats were randomized into
      control group (n=13), model group (n=19) and EA group (n=19). Obesity model was
      duplicated by feeding the rats with high fat forage and subcutaneous injection of
      15% glutamate sodium solution. EA (100 Hz, 3-5 mA) was applied to "Housanli" (ST
      36), "Sanyinjiao" (SP 6), "Guanyuan" (CV 4) and "Zhongwan" (CV 12) for 10 min
      everyday and for 28 days. Lee's index, body weight, area and the number of the
      adipose cells around the left kidney were detected. Blood samples were collected
      for assaying serum triglyceride (TG), total cholesterol (TC) with cholesterol
      oxidase phenol 4-aminoantipyrine peroxidase (CHOD-PAP) method, glycerol phosphate
      oxidase-p-aminophenazone (GPO-PAP) methods, high density lipid-cholesterol (HDL
      C) with phosphotungstic acid- Mg2+ method, low density lipid-cholesterol (LDL-C)
      with polyvingel sulfate (PVS) sedimentation method and plasma lipoprotein lipase
      (LPL) with immunoturbidmetry endpoint method, and serum insulin and leptin
      contents with radioimmunoassay respectively. RESULTS: After modeling, in
      comparison with control group, Lee's index, serum TG, TC, LDL-C, fat weight,
      adipose cell area, serum leptin and insulin contents in model group increased
      considerably (P<0.05, 0.01), while serum HDL-C, plasma LPL, adipose cell number
      decreased significantly (P<0.05, 0.01). Following EA, compared with model group,
      Lee's index, serum TG, TC, LDL-C, fat weight, adipose cell area, serum leptin and
      insulin levels decreased significantly in EA group (P<0.05, 0.01), whereas serum
      HDL-C, plasma LPL, and adipose cell number increased apparently (P<0.01).
      CONCLUSION: High frequency EA can effectively improve abnormal lipid metabolism,
      and reduce fat accumulation in obesity rats, which may be closely associated with
      its effect in regulating the balance between leptin and insulin levels.

PMID- 18807716
TI  - [Correlation between the therapeutic efficacy of electroacupuncture of ear-body
      acupoints and mast cells in experimental gastric ulcer rats].
AB  - OBJECTIVE: To study the interrelation between the therapeutic efficacy of
      electroacupuncture (EA) and mast cells (MC) in experimental gastric ulcer rats.
      METHODS: Thirty Wistar rats were randomly divided into normal control group,
      model group and EA group, with 10 cases in each. Experimental gastric ulcer model
      was established by injecting 20% glacial acetic acid (0.05 ml) into the tissue
      between the muscular layer and the placenta percreta of the gastric anterior wall
      in the gastric antrum under anesthesia. EA (2/15 Hz, 1 mA) was applied to
      bilateral "Wei" (Stomach, an otopoint) and "Zusanli" (ST 36) for 30 min, once
      daily for 7 days. The tissues of these two acupoints were sampled to be stained
      with acetylcholine esterase (AChE) and toluidine blue (TB) respectively
      (counterstaining) after section (15 microm). The gastric ulcer tissue was stained
      with H&E method RESULTS: Compared with control group, the number and
      degranulation ratios of MC in the dermis of "Wei"-point and ST36 region in model
      group and EA group increased significantly (P<0.01); while in comparison with
      model group, both the number and the degranulation ratio of MC in EA group
      decreased considerably (P<0.01). H&E stained tissues showed smooth gastric
      mucosal membrane in control group, ulcerative injury involving the muscular layer
      in model group, and mild injury in EA group. CONCLUSION: EA can suppress the
      degranulation of MC in "Wei"-point and ST36 regions and effectively relieve
      ulcerative injury in gastric ulcer rats. There exists a certain degree of
      interrelation among the degranulation ratio of MC, gastric ulcerative injury, and
      the therapeutic efficacy.

PMID- 18807717
TI  - [Involvement of melatonin in the adjusting effect of electroacupuncture in
      resisting oxygen stress in cerebral ischemia-reperfusion injury rats].
AB  - OBJECTIVE: To explore the effect of electroacupuncture (EA) in resisting acute
      cerebral ischemia-reperfusion injury (CI-RI) via anti-oxidation of melatonin
      (MT). METHODS: A total of 52 male SD rats were randomized into Sham-operation
      (sham, n=8), CI-RI (model, n=8), EA (n=8), MT (3.2 mg/Kg, i.p., n=8), EA+MT
      (n=8), EA+Luzindole (L, a blocker of MT, 1 mg/100 microl/rat, n=6), EA+PD 98059
      (a blocker of mitogen-activated protein kinase, MAPK, 1 mg 100 microl/rat, n=6)
      groups. EA (3 Hz,1-3 mA, continuous waves) was applied to "Dazhui" (GV 14) and
      "Baihui" (GV 20) for 30 min. CI-RI model was induced by right middle cerebral
      artery occlusion (MCAO) for 60 min and reperfusion for 24 h except sham-operation
      group. MT content of pineal gland tissue was determined by high performance
      liquid chromatography (HPLC) and neuroethological scores of the rats were
      evaluated by Kuluz's and Julio's methods. Bax and Bcl-2 gene protein expression
      of the striate body was detected by immunohistochemistry. RESULTS: In comparison
      with sham group, the number of Bax immunoreactive (IR) positive cells and Bax/Bcl
      2 in striate body increased significantly (P<0.001), and neuroethological score
      and Bcl-2 IR-positive cells decreased considerably in model group (P<0.01).
      Compared with model group, pineal MT content, neuroethological score and Bcl-2 IR
      positive cells in EA group, neuroethological scores in EA+L and EA+P groups, and
      Bcl-2 expression in MT and EA+MT groups increased considerably (P<0.01, 0.001);
      while Bax IR-positive cells and Bax/Bcl-2 in EA, MT and EA+MT groups decreased
      very significantly (P<0.001). It showed that EA could obviously increase pineal
      MT content, improve CI-RI rats' activity score, upregulate Bcl-2 expression and
      down-regulate Bax expression in striate body. In comparison with simple EA group,
      neuroethological scores of EA+L and EA+P groups, Bax IR-positive cells and
      Bax/Bcl-2 of EA+MT group were significant lower (P<0.05, 0.01). No significant
      differences were found between EA+L and EA+P groups in behavior scores, and
      between MT and EA+MT groups in Bax and Bcl-2 IR-positive cell number and Bax/Bcl
      2 (P>0.05). CONCLUSION: EA has a good effect of anti-oxygen stress, protecting
      the brain from ischemic damage directly or indirectly, which may be related to
      its effect in upregulating the synthesis and release of MT.

PMID- 18807718
TI  - [Effect of electroacupuncture of different acupoints on plasma and cerebral
      endothelin and CGRP contents in acute cerebral ischemia rats].
AB  - OBJECTIVE: To investigate the underlying mechanism of electroacupuncture (EA) of
      "Shuigou" (GV 26) and "Baihui" (GV 20), "Ganshu" (BL 18) and "Shenshu" (BL 23) in
      resisting cerebral ischemia (CI). METHODS: Sixty male SD rats were randomly
      divided into pseudo-operation group, model group, GV26-GV20 group, and BL18-BL23
      group, with 15 cases in each. CI model was established by middle cerebral artery
      occlusion (MCAO). EA (2/30 Hz,2 mA) was applied to GV26, GV20, BL18 and BL23 for
      30 min every time and for 6 times. Neuroethologic scores of the rats were
      evaluated, plasma and cerebral endothelin (ET) and calcitonin gene-related
      peptide (CGRP) contents were determined by radioimmunorassay. RESULTS: 1) After
      MCAO for 72 hours, the rats' neuroethologic score, plasma and cerebral ET
      contents in model group increased significantly in comparison with those of
      pseudo-operation group (P<0.05, 0.01), and plasma and cerebral CGRP levels
      decreased considerably (P<0.01). Compared with model group, the neuroethologic
      scores, cerebral ET contents of GV26-GV20 and BL18-BL23 groups decreased
      significantly after CI (P<0.01); and plasma and cerebral CGRP levels in two EA
      groups increased significantly (P<0.05, 0.01). No significant differences were
      found between two EA groups in these 3 indexes (P>0.05). CONCLUSION: EA of GV26
      GV20 and BL18-BL23 can improve CI rats' behavior activity, which may be related
      to its effects in lowering cerebral ET and raising blood and cerebral CGRP
      levels.

PMID- 18807719
TI  - [Effect of scalp-acupuncture on plasma and cerebral TNF-alpha and IL-1beta
      contents in acute cerebral ischemia/reperfusion injury rats].
AB  - OBJECTIVE: To explore the underlying mechanism of scalp-acupuncture therapy in
      the treatment of acute cerebral ischemia (ACI) in the rat. METHODS: A total of
      140 SD female rats were randomly assigned to sham-operation (n=20), model (n=60),
      scalp-acupuncture (SA, n=60) groups, and the later two groups were further
      divided into 24 h, 48 h and 72 h subgroups separately, with 20 cases in each.
      Among them, 70 rats were used for cerebral tissue section, and the other 70 cases
      for homogenating cerebral tissue. ACI model was established by occlusion of the
      middle cerebral artery (MCAO) for 1 h and reperfusion. EA (2/100 Hz, 2 mA) was
      applied to bilateral "Dingnie Houxiexian" (MS 7) and "Dingnie Qianxiexian" (MS 6)
      for 20 min, once daily for 1 d, 2 d and 3 d respectively. The rat's neurological
      severity score (NSS) was assessed before and after EA. Blood and brain tissue
      were sampled for detecting TNF-alpha and IL-1beta contents respectively with
      enzyme-linked immunosorbent assay. Haematoxylin-eosine (H&E) staining method was
      used for displaying the inflammatory cells in the ischemic brain tissue. RESULTS:
      (1) After ACI, NSS at each time-point increased significantly, while compared
      with model group, NSS of SA group decreased apparently 72 h after ACI (P<0.01).
      Compared with the corresponding time-points of sham-operation group, the number
      of inflammatory cells, plasma and cerebral TNF-alpha and IL-1beta contents at 24
      h, 48 h and 72 h in model group increased considerably (P<0.01, 0.05). In
      comparison with the corresponding time-points of model group, the number of
      inflammatory cells at 48 h and 72 h, plasma and cerebral TNF-alpha and IL-1beta
      contents at 72 h in SA group declined significantly (P<0.01). CONCLUSION: Scalp
      acupuncture can relieve inflammatory cell infiltration, and reduce plasma and
      cerebral TNF-alpha and IL-1beta contents in ACI rats, which may contribute to its
      effect in promoting neurofunctional recovery.

PMID- 18807720
TI  - [Effect of connexin 43 knockout on acupuncture-induced down-regulation of c-fos
      expression in spinal dorsal horn in visceral pain mice].
AB  - OBJECTIVE: To explore the effect of connexin 43 gene knockout on acupuncture
      analgesia. METHODS: Seventy-two wide type (WT) and connexin 43 gene knockout mice
      were separately and randomly divided into: WT control group, WT model group, WT
      acupuncture group, heterozygous (HT) control group, HT model group and HT
      acupuncture group, with 12 cases in each. Visceral pain model was established by
      intraperitoneal administration of acetic acid. "Zhongwan" (CV 12) and bilateral
      "Zusanli" (ST 36) were punctured with a filiform needle for 30 min and stimulated
      by manipulating the needle 30 s every 5 min. The expression of c-fos in the
      spinal dorsal horn was assayed by using RT-PCR and western blot techniques.
      RESULTS: There was no significant difference between HT and WT control mice in
      relative grey value of spinal c-fos mRNA expression (P>0.05), in which few c-fos
      mRNA and protein expressed. The expression of c-fos mRNA and protein was
      increased significantly following intraperitoneal acetic acid injection compared
      with control groups in both HT and WT mice (P<0.01). And no significant
      difference was found between HT and WT model groups in c-fos mRNA expression
      (P>0.05). Compared with WT model group, the expression of both c-fos mRNA and c
      fos protein in WT acupuncture group was down-regulated significantly (P<0.01). In
      comparison with HT model group, the expression of both c-fos mRNA and protein in
      HT acupuncture group was down-regulated but without statistically significant
      difference (P>0.05). And the expression of c-fos mRNA and protein in HT
      acupuncture group was significantly higher than that in WT acupuncture group
      (P<0.05, 0.01). CONCLUSION: Acupuncture has a marked antinociceptive effect in
      visceral pain mice, and simultaneously suppresses the expression of c-fos mRNA
      and protein evoked by noxious stimulation in the spinal dorsal horn. Connexin 43
      gene knockout may weaken acupuncture analgesia and reduce EA-induced down
      regulation of c-fos expression, suggesting an involvement of connexin 43 in the
      analgesic effect of acupuncture.

PMID- 18807721
TI  - [Effect of electroacupuncture of "Hegu" (LI 4)-"Taichong" (LR 3) on colonic
      nitric oxide synthase and glutathione peroxidase activity and nitric oxide
      content in depression rats].
AB  - OBJECTIVE: To observe the effect of electroacupuncture (EA) on the activity of
      inducible nitric oxide synthase (iNOS), glutathione peroxidase (GSH-Px) and the
      content of nitric oxide (NO) in colon tissue of depression rats, so as to reveal
      its mechanism in protecting colonic tissue under depression. METHODS: Forty male
      SD rats were equally randomized into normal, model, medication and EA groups.
      Depression model was established by using chronic unpredictable mild stress
      stimulation (forced ice-water swimming, electric shock, tail-clamping, etc)
      combined with lonely raising for 21 days. At the same time of modeling,
      Fluoxetine (1.8 mg/kg, intragastric perfusion) was given to the rats of
      medication group, once daily for 21 days. EA (1.5-2 Hz, 1-3 mA) was applied to
      bilateral "Hegu" (LI 4) and "Taichong" (LR 3) for 20 min, once daily for 21 days.
      The activity of iNOS, GSH-Px and the content of NO in colon tissue were detected
      by ultraviolet spectrophotometer method. RESULTS: In comparison with normal
      control group, iNOS activity and NO content in colon tissue increased
      significantly (P<0.05), and GSH-Px activity decreased considerably (P<0.05) in
      model group. Whereas compared with model group, iNOS activity and NO content
      decreased significantly (P<0.05), and GSH-Px activity increased significantly in
      EA and medication groups. No significant differences were found between EA group
      and medication group in these 3 indexes (P>0.05). CONCLUSION: EA of "Hegu" (LI 4)
      and "Taichong" (LR 3) can reduce stress induced increase of both iNOS activity
      and NO content, and decrease of GSH-Px activity in colon tissue in depression
      rats, which may contribute to its effect in protecting the digestive tract from
      injury under depression.

PMID- 18807722
TI  - [Impact of different emulated acupuncture-needle manipulations on blood pressure
      and myocardial angiotensin II content in spontaneous hypertension rats].
AB  - OBJECTIVE: To observe the effect of different emulated acupuncture-needle
      manipulations on blood pressure and myocardial angiotensin (Ang) II content in
      spontaneously hypertensive rats (SHR), so as to seek a better acupuncture
      parameter for clinical treatment of hypertension. METHODS: Thirty-three SHR were
      randomly divided into mild-stimulation group (n=8), moderate-stimulation group
      (n=8), heavy-stimulation group (n=8) and model group (n=9). Additionally, other 8
      normal rats were made up of control group. Blood pressure (BP) was determined by
      using a non-invasive BP detection system. Myocardial Ang II content was assayed
      by radioimmunoassay. The emulated acupuncture-needle twirling angles and
      frequencies of 144 degrees, 75 r/min; 255 degrees, 111 r/min; and 360 degrees,
      140 r/min in mild, moderate and heavy manipulations were applied to bilateral
      "Zusanli" (ST 36) and "Taichong" (LR 3) for 3 min, once daily for 3 weeks, with
      an interval of 2 days between every two weeks. RESULTS: Compared with pre
      therapy, BP values of both heavy-stimulation and model groups increased
      significantly (P<0.01); and compared with model group, BP values of mild
      stimulation and moderate-stimulation groups decreased significantly after the
      therapy (P<0.05), but were still higher than that of control group (P<0.05). In
      addition, myocardial Ang II contents of mild-stimulation, moderate-stimulation,
      heavy-stimulation and model groups were significantly higher than that of control
      group (P<0.05). No significant differences were found between mild-stimulation
      and moderate-stimulation groups, and between heavy-stimulation and model groups
      after therapy in BP, and among mild-stimulation, moderate-stimulation, heavy
      stimulation and model groups in myocardial Ang II contents (P>0.05). CONCLUSION:
      Mild and moderate manipulations of ST36 and LR3 have apparent influence on BP,
      but no apparent influence on myocardial Ang II content.

PMID- 18807723
TI  - [Study on the visualization of the Lung Meridian of Hand-Taiyin].
AB  - OBJECTIVE: To display the Lung Meridian of Hand-Taiyin at the body surface in a
      virtual human. METHODS: After defining the acupoints as the control points, chose
      suitable function interpolation to compose skeleton curve, actualize surface
      rendering and to rebuild a tube-like meridian model. RESULTS: The rebuilt tubular
      meridian model had a good visual effect, and clearly showed different anatomic
      structures of the Lung Meridian of Hand-Taiyin. CONCLUSION: We primarily and
      successfully accomplish the visualization display of the Lung Meridian of Hand
      Taiyin in a virtual human, which affords a data carrier for building a meridian
      research platform.

PMID- 18807724
TI  - [Utilizing modern technology to promote spread and development of acu-moxibustion
      learning].
AB  - Nowadays, modern information technology (IT) has been gained great development.
      How to use the advanced IT to protect, spread and develop Chinese traditional
      culture of acupuncture is an important topic at the moment. Based on expounding
      characteristics of modern IT, the present article analyzed its advantages in
      digitalizing, exhibiting and sharing the rich resources of acu-moxibustion.
      Particularly, through introduction of concrete examples of "Digital Museum
      (Gallery) of Acu-moxibustion", this paper may provide a useful enlightenment for
      digitalizing construction of acu-moxibustion resources and promoting the further
      spread and development of acu-moxibustion learning by utilizing modern IT.

PMID- 18807725
TI  - [Clinical randomized study of bee-sting therapy for rheumatoid arthritis].
AB  - OBJECTIVE: To observe the clinical effect of bee-sting (venom) therapy in the
      treatment of rheumatoid arthritis (RA). METHODS: One hundred RA patients were
      randomly divided into medication (control) group and bee-venom group, with 50
      cases in each. Patients of control group were treated with oral administration of
      Methotrexate (MTX, 7.5 mg/w), Sulfasalazine (0.5 g,t. i.d.), Meloxicam (Mobic,7.
      5 mg, b. i. d.); and those of bee-venom group treated with Bee-sting of Ashi
      points and the above-mentioned Western medicines. Ashi-points were selected
      according to the position of RA and used as the main acupoints, supplemented with
      other acupoints according to syndrome differentiation. The treatment was given
      once every other day and all the treatments lasted for 3 months. RESULTS:
      Compared with pre-treatment, scores of joint swelling degree, joint activity,
      pain, and pressing pain, joint-swelling number, grasp force, 15 m-walking
      duration, morning stiff duration in bee-venom group and medication group were
      improved significantly (P<0.05, 0.01). Comparison between two groups showed that
      after the therapy, scores of joint swelling, pain and pressing pain, joint
      swelling number and morning stiff duration, and the doses of the administered MTX
      and Mobic in bee-venom group were all significantly lower than those in
      medication group (P<0.05, 0.01); whereas the grasp force in been-venom group was
      markedly higher than that in medication group (P<0.05). In addition, the relapse
      rate of bee-venom group was obviously lower than that of medication group
      (P<0.05; 12% vs 32%). CONCLUSION: Combined application of bee-venom therapy and
      medication is superior to simple use of medication in relieving RA, and when bee
      sting therapy used, the commonly-taken doses of western medicines may be reduced,
      and the relapse rate gets lower.

PMID- 18807726
TI  - [Comparison of therapeutic effects of electroacupuncture treatment of insomnia at
      different time].
AB  - OBJECTIVE: To compare the therapeutic effects of evening-electroacupuncture (EA)
      and morning-EA for insomnia. METHODS: Sixty cases of simple insomnia patients
      were randomly divided into evening-EA group and morning-EA group, with 30 cases
      in each. EA (2/100 Hz, 1-3 mA) was applied to Baihui (GV 20), Shenting (GV 24),
      Touwei (ST 8), Shenmen (HT 7), Sanyinjiao (SP 6), etc. in the evening (8:00-9:00
      pm) and in the morning (8:00-11:00 am) respectively in two groups, once daily for
      10 times. Changes of mean global Pittsburgh Sleep Quality Index (PSQI), sleep
      rate, frequency of hypnotic-taking, etc were observed before and after the
      treatment. RESULTS: In comparison with pre-treatment, mean PSQI scores in evening
      EA and morning-EA groups, and hypnotic-taking frequency in evening-EA group
      decreased evidently during two weeks after the treatment, and sleep rates of two
      groups increased significantly from the 1st day on after the treatment in evening
      EA group and from the 1st week on in morning-EA group (P<0.01). Comparison
      between two groups showed that the mean PSQI scores at the 1st and 2nd week in
      evening-EA group were significantly lower, and the sleep rate in evening-EA group
      on the 2nd week after the treatment was considerably higher than that in morning
      EA group (P<0.05). CONCLUSION: Evening-EA can significantly lower insomnia
      patients' PSQI score, raise sleep rate, and reduce the hypnotic-taking frequency.
      Evening-EA is superior to morning-EA in the treatment of insomnia.

PMID- 18807727
TI  - [Clinical and qualitative research on acu-moxibustion: considerations on
      acupuncture clinical trail methods].
AB  - Qualitative research refers to a generic name of research methods corresponding
      to the quantitative research. It is different from quantitative research not only
      in methods, properties of the collected data, but also and particularly in
      philosophy, ideology and epistemology. In the present paper, the authors make a
      brief introduction about the background and methodology of qualitative research,
      and forecast the future possible tendency of the combined clinical trails of acu
      moxibustion. Hopefully, it may provide a possible model for acupuncture clinical
      research methods and make the acupuncture researchers understand the qualitative
      research methods in clinical practice so as to promote the further development of
      acupuncture clinical trails, improve the level of acupuncture theory and provide
      substantial acupuncture clinical evidence.

PMID- 18807728
TI  - [Progress in the research of neuroendocrine-immunological mechanism of
      acupuncture in regulating blood pressure and protecting target organs in
      hypertension].
AB  - By ways of favorable bi-directionally-regulative effect of acupoint stimulation
      and close correlation between acupoints and Zangfu-organs, acupuncture therapy
      can effectively regulate both blood pressure and functional activities of the
      corresponding viscera. Hence, acupuncture therapy, as a complementary method for
      hypertension, has its characteristics in protecting target organs. In the present
      paper, the authors review the progress in acupuncture treatment of hypertension
      in recent ten years from the studies of clinical treatment and animal
      experiments; analyze the underlying mechanism of acupuncture in protecting target
      organs of hypertension from the neuro-endocrine-immune network. Moreover, the
      authors point out some existing problems and put forward a few suggestions about
      acupuncture research in this field.

PMID- 18807729
TI  - [Effect of nitric oxide on noradrenergic function and skin electric resistance of
      acupoints and meridians].
AB  - Most acupuncture points correspond to low skin-resistance points (LSRP) on the
      body surface along the meridians. We did three experiments which conformed that
      the skin nitric oxide (NO) concentration and expression of neuronal nitric oxide
      synthesis (nNOS) were higher than those in non-acupoints, and non-meridian
      control points. Noradrenaline (NE) synthesis/release was modulated by exogenous
      NO donor and selective inhibitor of nNOS in the skin acupoints/meridians. Skin
      electrical currents in low skin resistance points were modified by L-arginine
      derived NO synthesis and NE. As a conclusion, NO-NE contribute to low resistance
      characteristics of acupoints and meridians.

PMID- 18807730
TI  - [Unexpected admission to the intensive care unit following ambulatory surgical
      procedures].
AB  - INTRODUCTION: Unexpected admission (UA) to the intensive care unit (ICU) among
      the ambulatory patient could be considered as an indicator of quality of
      attention on ambulatory services. However, the determinants associated with this
      rare complication are unknown. Objective. To identify the factors associated with
      UA to the ICU among the patients following ambulatory surgical procedures (ASP).
      MATERIAL AND METHODS: Twenty one cases and 105 controls were selected from among
      4,705 patients admitted for an ASP at a teaching hospital between January 2004
      and May 2006. A case was that one with an UA to the ICU for monitoring and/or
      treatment after its ambulatory surgical procedure. Each case was paired with five
      controls according to type of procedure and date of accomplishment. Conditional
      logistic regression analyses were used to determine the potential factors
      associated with an UA to the ICU. RESULTS: Cases represented 0.4% of admitted
      ones for an ASP. Mean age of controls were 46.9 years and 52.4% were women. There
      were no statistically significant differences between cases and controls in
      relation to several clinical, biochemical and physical status variables
      (comorbidity, vital signs, biochemistry, surgical procedure, anesthetic,
      technical anesthetic, time of surgery, surgical bleeding). Fourteen patients were
      less than 48 hours at the ICU and there were no deaths. CONCLUSIONS: Most of UA
      to the ICU seem to be based on decisions non-related to general health status of
      patients and these are usually preventive. This decision is not based on
      scientific evidence. Admission to the ICU must be based on a multidisciplinary
      evaluation.

PMID- 18807731
TI  - [Four years of raw mortality in an intensive care unit].
AB  - OBJECTIVE: To characterize magnitude and variability of raw mortality in a
      Mexican Intensive Care Unit (ICU). MATERIAL AND METHODS: Demographic and clinical
      data were analyzed in 1,746 patients discharged from the ICU of the Instituto
      Nacional de Ciencias Medicas y Nutricion Salvador Zubiran. The data was obtained
      from an administrative database and covered four years (2003-2006). RESULTS:
      Overall ICU-mortality was 23% (410/1746) and was associated with two binary
      variables (higher mortality in weekend admissions and non-surgical cases) and
      three multicategorical variables (gradient of increasing mortality with
      increasing age, increasing diagnostic risk and increasing number of high-rish
      diagnoses). First biennium mortality was significantly higher than in the second
      biennium (29% us 19%). This higher mortality was not associated with the high
      risk categories of the five variables described above nor with other ICU
      variables such as number of nurses and admission and discharge criteria. The only
      biennium difference was a higher number of physicians (specialists + residents)
      in the second biennium (16-20 versus 14-15 in the first). CONCLUSIONS: The four
      year long-term ICU-mortality showed a significant decrease in the second
      biennium. Number of physicians was the only variable associated with the
      decreased mortality.

PMID- 18807732
TI  - Laparoscopic vs. open total mesorectal excision for treatment of rectal cancer.
AB  - INTRODUCTION: Because definitive long-term results are not yet available, the
      oncologic safety of laparoscopic surgery in rectal cancer remains controversial.
      Laparoscopic total mesorectal excision (LTME) for rectal cancer has been proposed
      to have several short-term advantages in comparison with open total mesorectal
      excision (OTME). However, few prospective randomized studies have been performed.
      OBJECTIVES: The main purpose was to evaluate whether there are relevant
      differences in safety and efficacy after elective LTME for the treatment of
      rectal cancer compared with OTME in a tertiary academic medical center. MATERIAL
      AND METHODS: This comparative non-randomized prospective study analyzes data of
      20 patients with middle and low rectal cancer treated with low anterior resection
      (LAR) or abdomino perineal resection (APR) from November 2005 to April 2006.
      Follow-up was determined through office charts or direct patient contact.
      Statistical analysis was performed using chi2 test and Student's t-test. RESULTS:
      Ten patients underwent LTME and 10 patients underwent OTME. No conversion was
      required in the LTME group. Mean operating time was shorter in the laparoscopic
      group (LTME) (186.7 vs. 204.4 min, p < 0.007). Less intraoperative blood loss and
      fewer postoperative complications were seen in the LTME group. An earlier return
      of bowel motility was achieved after laparoscopic surgery. There was no 30-day
      mortality and the overall morbidity was 20% in the LTME group vs. 40% in the OTME
      group. The mean number of harvested lymph nodes was greater in the laparoscopic
      group than in OTME group (10.2 +/- 2.5 vs. 8.3 +/- 3). Mean follow-up time was 12
      months (range 9-15 months). No local recurrence was found. CONCLUSION: LTME is a
      feasible procedure with acceptable postoperative morbidity and low mortality,
      however it is technically demanding. This series confirms its safety, while
      oncologic results are at present comparable to the OTME published series, with
      limitation of a short follow-up period though. Further randomized studies are
      necessary to evaluate long-term clinical outcome.

PMID- 18807733
TI  - Predictors of adverse surgical outcome in the management of malignant bowel
      obstruction.
AB  - INTRODUCTION: Malignant bowel obstruction (MBO) is a common problem in patients
      with advanced colorectal or ovarian cancer. The management of this group of
      patients is complex and controversial. OBJECTIVE: To analyze the factors
      associated with morbidity and mortality in patients who underwent surgery for MBO
      in a tertiary referral center in Mexico City. MATERIAL AND METHODS: Hospital
      records of patients who underwent surgery for malignant bowel obstruction from
      January 1987 through December 2005 were retrospectively analyzed. Demographic
      data, clinical and surgical variables were recorded. Morbidity and mortality
      within 30-day of surgical procedure were registered. Factors associated with
      outcome were analyzed with the chi-square test. Survival curves were constructed
      with the Kaplan-Meier method. RESULTS: One-hundred and thirty patients were
      included. Primary neoplasm was the cause of bowel obstruction in 51 (39.2%)
      patients. Resection and anastomosis was performed in 45 patients (34.6%); in 30
      cases (23.1%) a palliative estoma was constructed. Hospital mortality rate was
      10.8%, and major postoperative morbidity was 16.2%. Factors associated with a
      significant increase in surgical mortality were: advanced patient age 17.2% (p =
      0.009), hipoalbuminemia 14.45% (p = 0.027) and surgery performed for neoplasms
      different from those of gastrointestinal origin 17.6% (p = 0.005). Surgical
      morbidity was significantly higher in patients with poor performance status 16.2%
      (p = 0.017), advanced age 18% (p = 0.04), and low albumin levels 13.5% (p =
      0.03). Median survival for the entire cohort was nine months (95% CI 5-13).
      Actuarial one, three and five year survival were 38.4, 27.5 and 25.4%,
      respectively. The most significant predictor of survival was performance status.
      CONCLUSIONS: When surgical management of MBO is considered, a careful assessment
      of the factors shown here to predict an adverse surgical outcome and poor
      prognosis is required.

PMID- 18807734
TI  - How frequently the clinical practice recommendations for nephropathy are achieved
      in patients with type 2 diabetes mellitus in a primary health-care setting?
AB  - OBJECTIVE: To determine the proportion of DM2 patients in primary health-care
      setting who meet clinical practice recommendations for nephropathy. MATERIAL AND
      METHODS: 735 patients were included in this cross-sectional study. Nephropathy
      was defined as glomerular filtration rate < 60 mL/min/1.73 m2 or albuminuria > or
      = 30 mg/day. To estimate the proportion of patients meeting clinical practice
      recommendations, the achieved level was classified according to NKF -K/DOQI, ADA,
      IDF, JNC 7 report, and NCEP-ATPIII. RESULTS: A high frequency of kidney disease
      and cardiovascular risk factors (smoking, alcoholism, obesity) was observed.
      Adequate levels were attained in 13% for fasting glucose, 45% for blood pressure,
      71% for albuminuria, and 30% for lipids. Nephropathy was diagnosed in 41%.
      Adequate systolic blood pressure was observed in 40% of patients with nephropathy
      vs. 49% without nephropathy (p = 0.03). In both groups, body mass index was
      acceptable in one fifth of patients, and waist circumference in two thirds of men
      and one third of women (p = NS). Patients with nephropathy used more
      antihypertensives, particularly angiotensin converting enzyme inhibitors
      (nephropathy 49% vs. no nephropathy 38%, p = 0.004). Subjects with nephropathy
      received more frequently (p = 0.05) insulin (11%) than those without nephropathy
      (7%). In both groups, there was low use of statins (nephropathy 14% vs. no
      nephropathy 17%, p = 0.23), and aspirin (nephropathy 7% vs. no nephropathy 5%, p
      = 0.39). CONCLUSIONS: Recommended goals for adequate control of DM2 patients
      attending primary health-care units are rarely achieved, and this was independent
      of the presence of nephropathy. These findings are disturbing, as poor clinical
      and metabolic control may eventually cause that patients without nephropathy
      develop renal damage, and those subjects already with renal disease progress to
      renal insufficiency.

PMID- 18807735
TI  - [Does circumcision has an effect on female's perception of sexual satisfaction?].
AB  - OBJECTIVE: To evaluate sexual satisfaction on women who have experienced sexual
      intercourse with the same partner on non-circumcised and circumcised states.
      MATERIAL AND METHODS: A total of 19 women between 19 and 53 y/o, median age 30,
      in which their sexual partner was programmed for circumcision were included in
      this study. The survey was a validated version on the Changes on Sexual
      Functioning Questionnaire (CSFQ). General sexual satisfaction, pain during
      vaginal penetration, desire, vaginal orgasm, vaginal lubrication, sexual
      frequency changes in oral and/or anal sexual activities and esthetical perception
      on circumcised penis were surveyed before the procedure and 2 months after.
      RESULTS: Changes on Vaginal lubrication during intercourse were significant (p =
      0.004), it diminished from 78% to 63%. There were no statistically significant
      differences on general sexual satisfaction, pain during vaginal penetration,
      desire, vaginal orgasm. CONCLUSIONS: Circumcision has either negative or positive
      effect on female's partner perception of sexual satisfaction.

PMID- 18807736
TI  - [Distribution and relation of risk factors associated with eating disorders in a
      sample of pubescents, males and females, to 11-15 years old from Hidalgo,
      Mexico].
AB  - OBJECTIVE: To determine the distribution and relation of risk factors: biological
      (body mass index (BMI), sexual maturity) psychological (eating behaviours, body
      unsatisfied), and sociocultural (publicity influence and distress with body
      shape) factors associated to eating disorders in Mexican pubescent from Hidalgo,
      Mexico. MATERIAL AND METHODS: A field transversal descriptive and correlational
      design was carried away with a probabilistic sample of 2194 pubescent (males 48%;
      females 52%), between 11 and 15 years (X = 13.2; DE = 1.03) junior high students.
      A self-report questionnaire on eating behaviours, body image, sociocultural
      factors and sexual maturity was applied. BMI was obtained from each subject.
      RESULTS: The date showed that the majority (57% of females and 61.6% of males)
      was unsatisfied with their body shape as well as important percentages of
      distress of body shape (28% females; 14% males). Both females (25%) and males
      (16%) eliminate food times. About restrictive dieting the percentage between
      males (6%) and females (5.2%) were very similar. Only females showed
      preoccupation about weight and food (17.2%). As a BMI increased, unsatisfied with
      body shape (r = 0.552, p < 0.01) increased too. As well increased influence of
      publicity, distress of body shape increased too (r = 0.586, p < 0.01). These
      facts are deemed relevant to the etiophatology, prevention and treatment of
      eating disorders in Mexican pubescent.

PMID- 18807737
TI  - [Fluoride urinary excretion in Mexico City's preschool children].
AB  - OBJECTIVE: The assessment of urinary fluoride excretion during dental developing
      stage has been reported for different countries with community fluoride programs.
      Also, one of the factors that could influence on retention and excretion of
      fluoride is the deficient nutrition so the aim of this study was to determine
      fluoride urinary excretion by a group of preschool children with and without
      malnutrition. MATERIALS AND METHODS: Urinary samples from 24 hours were collected
      from 60 preschool children selected by convenience from Iztapalapa area of Mexico
      City, 30 with malnutrition and 30 with standard nutritrional status by weight for
      age. The samples were analyzed by fluoride especific electrode. Orion 720A.
      RESULTS: The average concentration of fluoride in urine from preschool children
      with and without malnutrition were 0.89 +/- 0.4 mg/L and 0.80 +/- 0.3 mg/L,
      respectively. The mean of 24 hours total fluoride excreted were 367 +/- 150
      microg/24 hrs. in malnutrition children and 355 +/- 169 microg/24 hrs. for those
      with standard nutritional status. There were no differences statistically
      significant between groups. CONCLUSION: The urinary fluoride excretion for
      children with and without malnutrition were in the optimal range of fluoridation
      for the prevention of caries decay. Malnutrition was no associated with changes
      on fluoride orine concentration and excretion rates.

PMID- 18807738
TI  - [Colon and rectum laparoscopic surgery].

PMID- 18807739
TI  - [Mutations in the arginine vasopressin neurophysin-II gene in familial
      neurohypophyseal diabetes insipidus patients].
AB  - Neurogenic diabetes insipidus (NDI) is a rare condition characterized by polyuria
      and polydipsia caused by deficient arginine vasopressin hormone production. More
      than a 50 mutations have been identified for familial autosomic dominant
      neurogenic diabetes insipidus (FadNDI). These mutations can cause citotoxicity
      and lead to the degeneration of magnocellular neurons of the hipofisis by
      aberrant protein accumulation. The NDI diagnosis is based on the water
      deprivation test, quantification of AVP hormone and Magnetic Resonance Image
      (MRI), and in families with history of FadNDI has been suggested the molecular
      analysis of mutation in the arginine vasopressin neurophisin II gene before the
      signs and symptoms development, with the purpose of offering a suitable
      diagnosis, clinical follow up and treatment. The treatment with a synthetic
      analogue of AVP hormone allows the remission of the signs and symptoms in NDI
      patients and the advances in gene therapy in animal models has been promising, as
      much for NDI as for other diseases in which the mutant protein production has
      been involved.

PMID- 18807740
TI  - [Spain, New Spain and the autopsy of an anatomic malformation].
AB  - Almost 250 years ago the autopsy of Agustin de Ahumada y Villalon was performed
      by Domingo Russi, Chief Surgeon at the Royal Hospital for Natives in Mexico City.
      This situation will be unimportant if the former wasn't the 42nd Viceroy of New
      Spain; his autopsy showed a situs inversus totalis, and probably this is the
      first scientific report of such malformation. For many years the report by Mathew
      Baillie (1761-1823) of an autopsy with the same findings as the first of its kind
      was believed, but actually the former almost three decades earlier was performed.
      In 1688 Jean M. Mery (1645-1722) at the Paris Academy of Medicine gave a talk
      reporting autopsy findings of the same malformations. Some aspects of the life of
      both personages are described, the autopsy report is showed and a short history
      about postmortem studies are mentioned mainly those made in Spain and New Spain.
      Through many centuries a very close relationship has been kept and medicine has
      not been the exception, in the field of human pathology in the middle third of
      the 20th century a distinguished pathologist, Dr. Isaac Costero-Tudanca, migrated
      to Mexico and gave flowering to pathology and a great generation of Mexican
      pathologists was generated headed by Dr. Ruy Perez-Tamayo.

PMID- 18807741
TI  - TB control programme--a way forward.

PMID- 18807742
TI  - Evaluation of different types of chest symptoms for diagnosing pulmonary
      tuberculosis cases in community surveys.
AB  - BACKGROUND: Prevalence of tuberculosis (TB) is an important epidemiological index
      to measure the load of the disease in a community. A series of disease surveys
      were undertaken in rural community in Tiruvallur district in Tamilnadu, south
      India OBJECTIVE: To investigate the yield of pulmonary tuberculosis (TB) cases by
      different symptoms status and suggest predominant symptoms for detection of cases
      in the community based surveys. METHODS: Three disease surveys were conducted
      during 1999-2006, in a random sample of 82,000 adults aged > or = 15 years to
      estimate the prevalence and incidence of pulmonary TB. All subjects were screened
      for chest symptoms and chest radiography. Sputum examination was done among those
      who were either symptomatic or abnormal on X-ray or both. Cases observed through
      symptom inquiry were included for analysis. RESULTS: In survey-I, 65.6% had cough
      of > or = 14 days and yielded 79.1% of the total cases. In surveys II and III,
      symptomatic subjects with cough contributed 69.5% and 69.2% of the cases
      respectively. In survey I, 26.8% had symptoms without cough but with at least
      chest pain > or = 1 month contributed 8.4% of total cases. The corresponding
      proportions in subsequent surveys were 29.3, 11.5%; and 23.4, 11.2% respectively.
      The number of symptomatics without cough and chest pain but with fever > or = 1
      month was negligible. CONCLUSION: The relative importance of cough as a
      predominant symptom was reiterated. The yield of pulmonary TB cases from
      symptomatics having fever of > or = 1 month was negligible. Fever may be excluded
      from the definition of symptomatics for screening the population in community
      surveys.

PMID- 18807743
TI  - DOTS in drug addicts with TB : Delhi experience.
AB  - BACKGROUND: Drug abuse is on the rise. Drug addiction lowers the general immunity
      of the body. Tuberculosis is known to be one of the major infectious diseases
      with a high incidence among drug addicts. Treatment of drug addicts suffering
      from tuberculosis is a challenge to the treating physician. METHODS: An
      interventional prospective study which involved free de-addiction drugs and
      motivation along with free anti tubercular drugs under Revised National
      Tuberculosis Programme was undertaken among drug addicts. Sixty drug addicts
      suffering from tuberculosis, registered under RNTCP in SPM marg TB Clinic (Pili
      Kothi) between 2002-2007 and treated under DOTS along with de-addiction treatment
      by an NGO (Sharan) formed the study sample. OBJECTIVES: Objectives of the study
      were: a) To study the profile of drug addicts with tuberculosis, b) To assess the
      success results of DOTS in drug addicts with tuberculosis (along with de
      addiction treatment). RESULTS: Extensive counselling for de-addiction and
      motivation of the study patients along with nutritional food supplements improved
      the compliance and adherence to treatment with equal success rates as in non
      addict tuberculosis patients. The overall success rate in drug addicts was 83.3%.
      The default rate of 3.3% and failure rate of just 1.7% among study group were
      also within the permissible range of RNTCP (< 4%). CONCLUSION: DOTS along with
      supplementary intervention was observed to be quite effective in drug addicts
      with TB.

PMID- 18807744
TI  - Is the quality of life different in patients with active and inactive
      tuberculosis?
AB  - OBJECTIVE: The aim of this study was to evaluate the quality of life (QOL) in
      outpatients with active and inactive tuberculosis, and to study the relations
      between QOL and demographic and socio-cultural chracteristics and variables
      concerning the disease and depression. MATERIAL AND METHODS: Included in the
      present study were 196 active and 108 inactive cases who attended Dispensary for
      Tuberculosis within a one year period, plus 196 healthy controls. In this study,
      questionnaire form, SF 36 quality of life scale and Beck Depression Inventory
      (BDI) were used. RESULTS: It was determined that in all fields of QOL, scores of
      the control group were higher than those of the patient groups. QOL scores in
      physical and social functionality dimensions of inactive cases were higher than
      in active cases (p < 0.001 ). As BDI scores increased in active and inactive
      cases, physical component summary (PCS) and mental component summary (MCS)
      decreased. As the treatment period increased in active cases, MCS increased. In
      active and inactive cases, marital status and accompanying diseases have an
      effect on the decrease of PCS scores (p < 0.05). In patients with tuberculosis,
      the QOL of men, single, patients with a high level of education and those not
      having a disease that accompanies tuberculosis were found to be high (p < 0.05).
      The QOL was negatively correlated with age and BDI, while being positively
      correlated with monthly income, daily sleep period and treatment period (p <
      0.05). CONCLUSION: It is stated that in inactive tuberculosis cases, as in active
      cases, QOL is deformed and demographic-socio cultural chracteristics, depression,
      daily sleep period, treatment period and accompanying diseases are factors that
      affect quality of life.

PMID- 18807745
TI  - Relationship of nitric oxide and protein carbonyl in tuberculosis.
AB  - BACKGROUND: Tuberculosis (TB) is a highly contagious disease caused by
      Mycobacterium tuberculosis. The bacilli replicate within the macrophages and can
      remain dormant for years; activated macrophages show immunity against these
      bacilli. MATERIAL AND METHODS: A prospective study was carried out in newly
      diagnosed TB patients (n = 70) before their antituberculosis treatment and in
      normal control subjects (n = 35). Serum level of nitric oxide was estimated by
      Moshage method, 1995 and Bories and Bories method, 1995 and protein carbonyl by
      Levine method, 1990. Pearson's correlation (r) and Fisher's 'z' test was
      performed on the obtained results. RESULTS: In our study, serum nitric oxide and
      protein carbonyl levels were significantly increased (p < 0.001) in TB patients
      as compared to normal control group. Positive correlation was seen in pulmonary
      TB (r = 0.8892, p < 0.001) [Fisher's 'z' transformed = 0.7901 to 0.9430] and
      extra-pulmonary TB (r = 0.8330, p < 0.001) [Fisher's 'z' transformed = 0.6918 to
      0.9128]; 'r' and Fisher's 'Z' was significantly different from zero (two sided p
      < 0.001). CONCLUSION: The mean serum nitric oxide and protein carbonyl levels
      were concomitantly increased and positively correlated with each other in
      patients with pulmonary TB and extra-pulmonary TB. The changes in the level of
      nitric oxide and protein carbonyl are a reflection of increased defence mechanism
      and free radical activity in tuberculosis.

PMID- 18807746
TI  - Status report on RNTCP.

PMID- 18807747
TI  - Scapholunate dissociation: a rare presentation of TB wrist in a case of multi
      focal skeletal tuberculosis.
AB  - Tuberculosis rarely involves wrist joint and is usually diagnosed in arthritic
      stage. Early presentations are easily confused with traumatic event and commonly
      missed. We describe a case presenting with scapholunate dissociation initially,
      which later progressed to full blown arthritis. Similar presentation has never
      been documented.

PMID- 18807748
TI  - An unusual case of a pleural effusion with an abdominal mass.
AB  - A 38-year-old man presented to us with a left sided pleural effusion. Pleural
      fluid was aspirated and analysis revealed it to be an exudate with predominant
      lymphocytes and an elevated ADA level. He was discharged on antituberculous
      treatment. Patient returned with re-accumulation of pleural fluid. Computed
      tomography done in our institute picked up not only parenchymal disease in the
      lung which was not evident on chest radiographs but also picked up an abdominal
      mass in the left renal fossa. Pathological examination of excised mass revealed
      its tuberculous nature. The repeated recollection of pleural fluid was attributed
      to a "paradoxical response"; the patient was reassured and his anti-tuberculous
      treatment continued. Recognition of the fact that evidence of tuberculosis at
      distant sites may occasionally be needed to substantiate the diagnosis of
      tuberculous pleural effusion in a difficult and bacteriologically "negative" case
      prompted us to report this case.

PMID- 18807749
TI  - Annual risk of tuberculosis infection in Chennai city.
AB  - AIM: To study the proportion of children infected with Mycobacterium Tuberculosis
      in Chennai city. METHODOLOGY: A cluster sampling methodology was adopted to
      select an estimated sample size of 7000 children from five corporation zones
      selected systematically from ten zones of the city. A total of 7098 children aged
      1-9 years were subjected to Mantoux and test read; 1897 (27%) from slum area and
      5201 (73%) from non-slum area. RESULTS: The prevalence of infection among
      children without BCG scar was estimated to be 10.5 % (ARTI of 2.0%) and was
      similar to that among children irrespective of scar status. The prevalence of
      infection was higher among children in slum areas (11.1%; ARTI 2.1%) compared to
      non-slum areas (8.9%; ARTI 1.7%); but the difference was not statistically
      different. CONCLUSION: The tuberculosis situation in Chennai as measured by risk
      of infection was higher in urban city area than rural areas and comparable to
      that found in other cities as reported from earlier studies. This information can
      be used as baseline information for monitoring the epidemiological trends in
      Chennai city in future.

PMID- 18807750
TI  - Tuberculosis and health care workers.

PMID- 18807751
TI  - Magnetic activated cell sorting (MACS): utility in assisted reproduction.
AB  - Assisted reproductive techniques (ART) have now been extensively incorporated in
      the management of infertile couples. But even after rapid methodological and
      technological advances the success rates of these procedures have been below
      expectations. This has led to development of many sperm preparation protocols to
      obtain an ideal semen sample for artificial reproduction. Sperm apoptosis has
      been heavily linked to failures in reproductive techniques. One of the earliest
      changes shown by apoptotic spermatozoa is externalization of phosphatidyl serine.
      Magnetic activated cell sorting (MACS) is a novel sperm preparation technique
      that separates apoptotic and non-apoptotic spermatozoa based on the expression of
      phosphatidylserine. This has led to the incorporation of MACS as a sperm
      preparation technique. The review highlights the principle and mechanism of this
      novel technique and enumerates its advantages as a sperm preparation technique.
      Its utility in ART as an efficient tool for sperm recovery and its application in
      cryopreservation of semen samples is also explained.

PMID- 18807752
TI  - Effect of DENA induced hepatocarcinogenesis on neuroendocrine levels in male
      rats.
AB  - Hepatocarcinogenesis was induced in Sprague Dawley rats by injecting
      diethylnitrosamine (DENA); 150 mg/kg body weight, ip, a well known liver
      carcinogen and a mutagenic agent. Concurrent with the induction of
      hepatocarcinoma, psychological stress was also elicited from the changes in brain
      neurotransmitters. Noradrenaline and dopamine, the neurotransmitters of
      sympathetic system were estimated from the whole brain and corresponding hormones
      T3, T4 and prolactin were estimated from the blood of such rats. The
      neuroendocrine cascade and the marker enzyme gamma glutamyl transferase were
      estimated at 7, 14, 21 and 30 weeks. A direct relationship between noradrenaline,
      T3 and T4 and a reciprocal relationship between dopamine and prolactin were
      observed, which may be correlated to the carcinogenic effect of DENA.

PMID- 18807753
TI  - Immunomodulatory activity of methanolic extract of Murraya koenigii (L) Spreng.
      leaves.
AB  - Immunomodulatory activity of methanolic extract of M. koenigii leaves was
      evaluated on humoral and cell mediated immune response to ovalbumin, phagocytic
      activity by carbon clearance test, nitric oxide (NO) release from murine
      peritoneal macrophages and cyclophosphamide induced myelosuppression. Significant
      increase in the NO production by mouse peritoneal macrophages was detected in
      culture supernatants indicated increased phagocytic activity of macrophages. The
      extract showed significant increase in phagocytic index by rapid removal of
      carbon particles from blood stream. The extract also increased the antibody titre
      against the ovalbumin and protection towards the cyclophosphamide induced
      myelosuppression. However, the extract did not show any significant increase in
      delayed type hypersensitivity reaction which indicated the inability of the
      extract to stimulate T cells. Present study thus reveals that the extract holds
      promise as immunomodulatory agent, which acts by stimulating humoral immunity and
      phagocytic function.

PMID- 18807754
TI  - Antioxidant and hepatoprotective activity of tubers of Momordica tuberosa Cogn.
      against CCl4 induced liver injury in rats.
AB  - Hydro alcoholic extract of tubers of M. tuberosa was subjected to preliminary
      phytochemical screening and evaluated for in vitro and in vivo antioxidant and
      hepatoprotective activity against CCl4 induced liver damage in rats. Pretreatment
      with 70% ethanolic extract of M. tuberosa reversed CCl4 induced elevation of
      levels of serum biomarkers to near normal levels, suggesting that the tubers of
      M. tuberosa possess hepatoprotective property and this property may be attributed
      to the antioxidant property of the plant.

PMID- 18807755
TI  - Effect of Phyllanthus niruri Linn. treatment on liver, kidney and testes in CCl4
      induced hepatotoxic rats.
AB  - Phyllanthus niruri extract is extensively used in treating liver ailments.
      Effects of aqueous extract of P. niruri on liver, kidney and testes of CCl4
      induced hepatotoxic rats were studied. High levels of malondialdehyde (MDA) were
      observed in the CCl4 test group with significant reduction of MDA levels in all
      groups on P. niruri extract administration. Highest levels of glutathione (GSH)
      were found in P. niruri group. Activities of alanine transaminase, aspartate
      transaminase and alkaline phosphatase enzymes were significantly reduced in the
      curative group (P. niruri treatment after CCl4 injection). Histopathology of
      liver showed lesser degree of inflammation in all P. niruri treated groups while
      the renal and seminiferous tubules showed eosinophilic protein casts with signs
      of tubular damage and degeneration. Testes also showed decreased amount of mature
      spermatozoa. The results suggest that P. niruri has anti-oxidant and hepato
      protective activity with associated deleterious effects on kidney and testes.

PMID- 18807756
TI  - Protective effect of Embelia ribes Burm on methionine-induced
      hyperhomocysteinemia and oxidative stress in rat brain.
AB  - The present study was aimed to find out the protective effect of ethanolic
      extract of E. ribes fruits on homocysteine, lactate dehydrogenase (LDH) and lipid
      profile in serum, lipid peroxidation (LPO) and non-enzymatic antioxidant
      glutathione (GSH) levels in brain homogenates and histopathological examination
      of brain tissue in methionine (1 g/kg body weight, orally for 30 days) induced
      hyperhomocysteinemic rats. A significant increase in homocysteine, LDH, total
      cholesterol, triglycerides, low density lipoprotein (LDL-C) and very low density
      lipoprotein (VLDL-C) levels was observed in serum. Increased LPO levels in brain
      homogenates with reduced serum high density lipoprotein (HDL-C) levels and
      decreased GSH content were other salient features observed in methionine treated
      pathogenic control rats. Administration of ethanolic E. ribes extract (100 mg/kg
      body weight, orally) for 30 days to methionine-induced hyperhomocysteinemic rats
      produced a significant decrease in the levels of homocysteine, LDH, total
      cholesterol, triglycerides, LDL-C, VLDL-C in serum and LPO levels in brain
      homogenates with significant increase in serum HDL-C levels and GSH content in
      brain homogenates, when compared with pathogenic control rats. Biochemical
      observations were further substantiated with histological examination of brain.
      Degenerative changes of neuronal cells in methionine treated rats were minimized
      to near normal morphology by ethanolic E. ribes extract administration as evident
      by histopathological examination. The results provide clear evidence for the
      first time, that ethanolic E. ribes extract treatment enhances the antioxidant
      defense against methionine-induced hyperhomocysteinemia and oxidative stress in
      brain.

PMID- 18807757
TI  - Protective effect of Piper longum L. on oxidative stress induced injury and
      cellular abnormality in adriamycin induced cardiotoxicity in rats.
AB  - Effect of methanolic extract of fruits of P. longum (PLM) on the biochemical
      changes, tissue peroxidative damage and abnormal antioxidant levels in adriamycin
      (ADR) induced cardiotoxicity in Wistar rats was investigated. PLM was
      administered to Wistar albino rats in two different doses, by gastric gavage (250
      mg/kg and 500 mg/kg) for 21 days followed by ip ADR (15 mg/kg) on 21st day. ADR
      administration showed significant decrease in the activities of marker enzymes
      aspartate transaminase, alanine transaminase, lactate dehydrogenase and creatine
      kinase in heart with a concomitant increase in their activities in serum. A
      significant increase in lipid peroxide levels in heart of ADR treated rats was
      also observed. Pretreatment with PLM ameliorated the effect of ADR on lipid
      peroxide formation and restored activities of marker enzymes. Activities of
      myocardial antioxidant enzymes like catalase, superoxide dismutase, glutathione
      peroxidase, glutathione reductase along with reduced glutathione were
      significantly lowered due to cardiotoxicity in rats administered with ADR. PLM
      pretreatment augmented these endogenous antioxidants. Histopathological studies
      of heart revealed degenerative changes and cellular infiltrations in rats
      administered with ADR and pretreatment with PLM reduced the intensity of such
      lesions. The results indicate that PLM administration offers significant
      protection against ADR induced oxidative stress and reduces the cardiotoxicity by
      virtue of its antioxidant activity.

PMID- 18807758
TI  - Modulatory effect of curcumin on methionine-induced hyperlipidemia and
      hyperhomocysteinemia in albino rats.
AB  - The present study was designed to investigate the antioxidant effect of curcumin
      on methionine-induced hyperlipidemia and hyperhomocysteinemia in Wistar rats (200
      250 g) of either sex. The vehicle control rats were treated with 1% Tween 80 in
      normal saline (2 ml/kg, po) for 30 days. Hyperlipidemia and hyperhomocysteinemia
      was induced by methionine administration (1 g/kg, po) for 30 days. A significant
      increase in total cholesterol, triglycerides, low density lipoprotein cholesterol
      (LDL-C) and homocysteine levels in serum and thiobarbituric acid reactive
      substances (TBARS) levels in heart homogenates were observed with a concomitant
      decrease in serum high density lipoprotein (HDL-C) levels in pathogenic control
      (i.e. group II) rats, as compared to vehicle control (i.e. group I) rats.
      Further, curcumin (200 mg/kg, p.o.) treatment in methionine treated rats for 30
      days significantly decreased the total cholesterol, triglycerides, LDL-C and
      homocysteine levels in serum and TBARS levels in heart homogenates and increased
      serum HDL-C levels, as compared to pathogenic control (i.e. group II) rats. The
      results of biochemical observations were supplemented by histopathological
      examination of rat's aortic section. The results of test drug were comparable to
      that obtained with folic acid (100 mg/kg, p.o.). The results suggest that
      curcumin has significant antihyperlipidemic and antihyperhomocysteinemic effect
      against methionine-induced hyperlipidemia and hyperhomocysteinemia in rats.

PMID- 18807759
TI  - Lowering of intraocular pressure by topical application of Daucus carota seed
      extract in rabbits.
AB  - In normotensive rabbits topical application of Daucus carota seed extract at the
      concentration of 0.3, 0.6 and 1.2% resulted in mean IOP reduction of 19.33. 23.20
      and 25.61% respectively from baseline. As no significant difference was observed
      between the change in IOP in 0.6 and 1.2% extract treated groups, 0.6%
      concentration was chosen for further evaluation in rabbits with experimentally
      elevated IOP. In water loaded rabbits, maximum mean IOP reduction with 0.6%
      extract was 29.39%, which was comparable to pilocarpine. In steroid pretreated
      rabbits, maximum mean IOP reduction was 30.27% from baseline, which was
      significantly higher than pilocarpine. The extract showed a comparatively slower
      onset of action however, the duration of action was comparable to pilocarpine in
      all the experimental models.

PMID- 18807760
TI  - Effect of Bacopa monniera (Linn.) on lipid peroxidation and lipofuscinogenesis in
      prostate gland of D-galactose induced aging mice, Mus musculus.
AB  - The levels of malondialdehyde and lipofuscin pigments were increased in the
      prostate of D-galactose (0.5 ml/day, sc, for 20 days) induced aging mice. After
      B. monniera (40 mg/kg body weight for 20 days) ethanol leaf extract
      administration levels of both the parameters were reduced significantly. The
      results suggest that B. monniera prevents formation of malondialdehyde and
      lipofuscin pigments which are the indicators of aging.

PMID- 18807761
TI  - Clinical market share. A recent KLAS report reveals who's king of the hill, and
      who's just treading water, in the clinical healthcare IT space.

PMID- 18807762
TI  - Building for the future. Embracing best practices can go a long way for CIOs
      involved in new facility construction.

PMID- 18807763
TI  - The real dynamic duo. CIOs are learning that a close relationship with their CFOs
      is a critical element of success.

PMID- 18807764
TI  - Linking the chain. Sisters of Mercy's highly successful supply chain is becoming
      a best practice in the healthcare industry.

PMID- 18807765
TI  - One-on-One with Healthia's Jim B-Reay. Jim B-Reay gives advice to CIOs striving
      to get their imaging architectures in order. Interview by Anthony Guerra.

PMID- 18807766
TI  - A win-win wireless plan. As the mobile device market becomes saturated with the
      latest and coolest gadgets, the CIO is tasked with cutting through the hype.

PMID- 18807767
TI  - The right plan? ONC's new strategic plan addresses key health IT issues, such as
      public reporting, but overall focus may be too broad.

PMID- 18807768
TI  - Biomed joins the party. Savvy CIOs are considering biomedical devices in their
      overall strategic plans.

PMID- 18807769
TI  - The price of success. To stand out in the evolving healthcare world, hospitals
      need to get their pricing in order.

PMID- 18807770
TI  - Opportunistic buyers. Despite the credit crunch, hospital chains cautiously eye
      new properties. Is a shopping spree around the corner?

PMID- 18807771
TI  - Manning the net. As one of Kansas City's few safety net hospitals, Truman Medical
      Center CFO Al Johnson must figure out how to pay for it all. Interview by Daphne
      Lawrence.

PMID- 18807772
TI  - Examining today's complex issues: from understanding racism to eliminating health
      disparities.

PMID- 18807773
TI  - A decision aid for teaching limitations of prostate cancer screening.
AB  - There is minimal research regarding men's knowledge of the limitations of
      prostate cancer screening. This study measured knowledge of prostate cancer
      screening based on exposure to one of two decision aids that were related to
      prostate cancer screening (enhanced versus usual care). The sample consisted
      primarily of low income (54%) African-American men (81%) (n=230). The enhanced
      decision aid was compared against the usual care decision aid that was developed
      by the American Cancer Society. The enhanced decision aid was associated with
      higher post-test knowledge scores, but statistically significant differences were
      observed only in the men who reported having had a previous DRE (p = 0.013) in
      the multivariable analyses. All the men were screened, regardless of which
      decision aid they received. This study highlights the impact of previous
      screening on education of the limitations of prostate screening, and challenges
      the assumption that increased knowledge of the limitations of prostate cancer
      screening will lead to decreased screening.

PMID- 18807774
TI  - Race, ethnicity, concentrated poverty, and low birth weight disparities.
AB  - This study examines the extent to which the relationship between area
      socioeconomic position (SEP) and low birth weight (LBW) varies by race and
      ethnicity. A cross-sectional, secondary data analysis was performed with 1992
      1994 Vital Statistics and 1990 U.S. Census data for selected metropolitan areas.
      Low birth weight (< 2500 grams) rates were calculated for non-Hispanic Black,
      Latino, and non-Hispanic White live singleton births. Concentrated poverty was
      defined as poor persons living in neighborhoods with 40% or more poverty in
      metropolitan areas. The results showed that the relationship between concentrated
      poverty and LBW varied by race and ethnicity. Concentrated poverty was
      significant for Latinos, even when controlling for maternal health and MSA-level
      factors. By contrast, maternal health characteristics, such as pre-term birth,
      teen birth and tobacco use, explained much of the variance in African-American
      and White LBW These findings extend the discussion about race, class, and health
      disparities to include Latinos and shows how the relationship between SEP and LBW
      can vary within an ethnic group.

PMID- 18807775
TI  - Risk and protection for HIV/AIDS in African-American, Hispanic, and White
      adolescents.
AB  - African-Americans and Hispanics are disproportionately affected by HIV/AIDS in
      the United States. HIV infection is often acquired during adolescence, a time
      when risky sexual behaviors are at their peak. This study explored relationships
      among selected risk factors, protective factors, and risky sexual behaviors among
      African-American, Hispanic, and White adolescents, from a sample of adolescents
      from the National Longitudinal Study of Adolescent Health. African-Americans and
      Hispanics were more likely to have sexual intercourse without the use of birth
      control than were Whites. African-Americans were more likely to have sexual
      behavior with multiple sexual partners than either Hispanics or Whites were, and
      African-Americans had higher self-esteem than did Hispanics and Whites. In order
      to develop culturally sensitive, effective interventions to prevent HIV/AIDS in
      adolescents, racial differences in risk and protective factors must be examined.

PMID- 18807776
TI  - Prevalence of traditional cardiovascular risk factors in African-American women
      with systemic lupus erythematosus (SLE): findings from the breakfast with a buddy
      biomarkers of lupus study.
AB  - African-American women are at high risk for systemic lupus erythematosus (SLE).
      Women with SLE are 5 to 8 times more likely to develop cardiovascular disease
      (CVD). The objective of this study was to characterize the prevalence of
      traditional CVD risk factors and the markers of sub-clinical atherosclerosis
      between African-American SLE cases (n=28) and controls (n=73). Significant
      differences were observed between SLE cases and controls in the areas of high
      blood pressure (68% of SLE cases, 42% of controls, p = 0.02), current smoking
      (18% of SLE cases, 15% of controls, p = 0.01), and average fasting glucose (85
      mg/dL in SLE cases, 98 mg/dL in controls, p = 0.02). SLE cases displayed non
      significantly higher HDL-c levels, lower LDL-c levels, and lower BMI. These
      results must be interpreted cautiously since the study sample was small and
      highly select. Larger studies are recommended to elucidate non-traditional
      mechanisms that may modulate some of the increased risk for CVD associated with
      SLE in women.

PMID- 18807777
TI  - African-American perceptions of health disparities: a qualitative analysis.
AB  - Health disparities, particularly in African-Americans, have been identified in a
      variety of settings. A secondary qualitative analysis of focus group data sought
      to describe African-American's perceptions of health disparities. Using an
      interpretive descriptive approach, three main levels of interaction within the
      health-care setting were identified that contained barriers to receiving the best
      possible care. The issue of finances was the major barrier that involved the
      insurance company, while racism, attitude, setting, and waiting were the major
      obstacles involved in the interaction in the health-care facility. The barriers
      present during the interaction with a personal provider were racism, a language
      barrier, and being rushed. Additionally, five ideals for patient-provider
      interaction were identified, as well as three approaches that the participants
      used to address the barriers within the health-care setting. A broad framework
      was developed incorporating these major themes.

PMID- 18807778
TI  - Opportunity cost: the impact of contextual risk factors on the cardiovascular
      health of low-income rural southern African-American women.
AB  - Low-income rural southern African-American women experience a high prevalence of
      morbidity and mortality from coronary heart disease (CHD) as well as other
      related cardiovascular (CV) diseases. Few models have taken into account the full
      impact of the contextual influences encountered on a daily basis by these women,
      and the effect of these influences on their CV health status. There are clearly
      demarcated examples of existing health disparities that occur in various
      ethnic/racial, underserved, and vulnerable populations. Yet, to date, there is no
      conceptual model that offers a plausible explanation as to why health disparities
      exist. Consequently, there is a lack of guidance as to where interventions should
      be focused for effective CV risk reduction. Because African-American women
      continue to die at a disproportionately higher rate, and at earlier ages than do
      White women, it is imperative that new theoretical models capable of driving
      empirically based interventions be developed, tested, and implemented. One
      possible choice is the conceptual model proposed in this article. The model is
      based on the interrelationships between contextual risk factors, rational choice
      theory (RCT), and opportunity cost. Conceivably, this model may serve as a
      foundation to ground conceptual thought and drive theory-based interventions to
      reduce the health disparities in the CV health of low-income rural southern
      African-American women. A model is presented in an attempt to provide guidance
      for advanced practice nurses who must struggle with addressing the critical need
      to reduce ethnic and race-associated CV health disparities.

PMID- 18807779
TI  - Management of cardiovascular disease in African-American women: utility of the
      metabolic syndrome guidelines.
AB  - Cardiovascular disease (CVD) is the leading cause of death in the Unites States
      and is disproportionately more prevalent among African-American women than
      members of other ethnic groups. The National Cholesterol Education Adult
      Treatment Panel III (ATP III) metabolic syndrome guidelines are useful in
      clinical practice to identify individuals who are at risk for developing CVD.
      Amendments to the ATP III criteria might be indicated to enhance early
      identification of CVD risk factors among African-American women, even when only
      one or two of the criteria are met. The addition of body mass index (BMI) and the
      identification of acanthosis nigricans as a marker of insulin resistance to the
      ATP III metabolic syndrome guidelines might facilitate early CVD risk
      identification, strategy implementation, and reduction of premature morbidity and
      mortality within this population.

PMID- 18807780
TI  - Understanding ethnopharmacolgy: implications for cultural relativism.
AB  - It is commonly accepted that people differ culturally. In the Giger and
      Davidhizar Transcultural Assessment Model, cultural differences are evident in
      communication, spatial relationships and needs, social organizations (church,
      family, kinships, and clubs), time orientation, the ability or desire to control
      the environment, and biological variations (Giger & Davidhizar, 2008). While many
      individuals appreciate that there are differences between cultures, what is less
      well recognized is that people also vary according to biological variations
      depending on their racial and ethnic group. In the last 15 years, information
      about biological variations has rapidly expanded and that knowledge is essential
      in order to understand and provide care to individuals from another culture or
      another racial and ethnic group. Attention to biological variations related to
      race and ethnicity, the last component of the Giger and Davidhizar Transcultural
      Nursing Assessment Model, is a critical phenomenon that needs to be assessed in
      order to develop and implement a culturally sensitive plan of care in an effort
      to understand ethnopharmacolgy.

PMID- 18807781
TI  - Strategic planning in the financing of school-based health clinics within urban
      communities.
AB  - Delivering health services within the school setting is not a new idea. School
      based health centers (SBHCs) are a widely accepted concept because they treat
      students for a broad range of physical, mental, and social health problems.
      Critics contend that schools should not involve themselves with students' non
      academic needs, yet, schools now more than ever are involved with their students'
      welfare because of the socio-economical environments they live in which they
      live. SBHCs realize that students are in no position to learn if their health
      care needs are substandard. They also recognize the health-care paradigm shift
      towards schools that serve as a central location where concerned health-care
      professionals can deliver care, prevention, and educational measures promoting
      healthy and academically successful students. SBHCs also empower the school's
      community by providing pertinent health information on topics that concern them
      or where the community's behavior patterns place them at risk. SBHCs receive
      funding from a variety of sources, including state, federal, boards of education,
      grants and private donations. Placing health-care services in schools assures
      students access to immediate care and guarantees that services rendered meets
      their diverse individual needs.

PMID- 18807782
TI  - Conceptualizing perceived racism and its effect on the health of African
      Americans: implications for practice and research.
AB  - The focus on racial health inequities has resurged. Although the reasons are
      complex, the consequences of racism are potentially contributing factors. This
      article aims to advance the concept of perceived racism as an area of focus for
      health inequity research by describing a framework within which to examine health
      outcomes that are associated with perceived racism. Perceived racism is defined
      as the subjective interpretation by the effected individual of an event,
      situation, or experience as negative, unjust, or undignified and one that solely
      occurs due to one's racial background. The framework establishes race as a
      determinant in health outcomes and it depicts the multidimensional contexts of
      racism. The model identifies physical, psychological, and behavioral pathways
      affecting health outcomes and personal, cultural, and social resources as
      mediating factors. Perceived racism can potentially permeate the lives of African
      Americans and can profoundly impact their health and well being. The principles
      of concept clarification were applied to explore the association between
      perceived racism and health.

PMID- 18807783
TI  - Harvard School of Dental Medicine: "a tradition of constant change".

PMID- 18807784
TI  - Boston: hub of the dental universe.

PMID- 18807785
TI  - Recollections of Tufts & Forsyth.

PMID- 18807786
TI  - Henry Goldman and dental education: reflections on the early days at Boston
      University.
AB  - Dental education at Boston University began in 1958 as an outgrowth of Henry M.
      Goldman's desire to create a university-based center for advanced graduate
      training in the dental specialties. By 1963, the Boston University School of
      Graduate Dentistry was established. Henry Goldman (1911-1991), an unwavering
      visionary, is largely responsible for the solid foundation on which is built the
      successful present-day Goldman School of Dental Medicine at Boston University.

PMID- 18807787
TI  - The transformation of the American Association of Oral Surgeons into the American
      Association of Oral and Plastic Surgeons.

PMID- 18807788
TI  - A periodontal incident at the Battle of Marathon.

PMID- 18807789
TI  - Employers' liabilities for bullying-induced psychiatric injuries.
AB  - Important opportunities exist for employees who are bullied in the work place to
      take civil action against employers for failing to provide them with a safe work
      environment. However, many logistical impediments lie in the way of successful
      actions for harm caused by bullying. This editorial scrutinises two important
      cases, Naidu v Group 4 Securitas Pty Ltd [2005] NSWSC 618; Nationwide News Pty
      Ltd v Naidu; ISS Security Pty Ltd v Naidu [2007] NSWCA 377 and Green v DB Group
      Services (UK) Ltd [2006] EWHC 1898 where workers were successful in such actions
      and explores the repercussions of their success.

PMID- 18807790
TI  - The United Nations Convention on the rights of persons with disabilities.
AB  - The United Nations Convention on the Rights of Persons with Disabilities, which
      came into force on 3 May 2008, marks the culmination of over five years of
      negotiations between States Parties and non-governmental organisations as to what
      constitute the human rights of and governmental obligations to individuals with
      disabilities. It differs from other Conventions in that, while it still sets out
      general rights, it also details the steps that should be taken to ensure equality
      of treatment. This column provides a general overview of the Convention, focusing
      in particular on Art 25 which sets out the right to health and Australia's
      obligations under the Convention.

PMID- 18807791
TI  - The use of the term "obesity" in deaths reported to coroners in Australia.
AB  - There is growing government awareness of the increasing incidence of obesity in
      the Australian community and its potential impact on health policy issues. This
      column considers the appropriateness of the WHO definition of the term "obesity"
      and analyses its use by Australian forensic pathologists and coroners as a cause
      of death in "medical cause of death" statements. While families may have concerns
      about the use of this term in reference to a deceased family member, the use of
      "obesity" in medical cause of death statements could have considerable influence
      on coroners' recommendations with regard to health policy in this area.

PMID- 18807792
TI  - Patient competence and professional incompetence: disagreements in capacity
      assessments in one Australian jurisdiction, and their educational implications.
AB  - The determination of capacity to make medical, personal and financial decisions
      has significant individual and social implications. Medical and other health
      professionals are traditionally relied on by courts and tribunals to provide
      clinical and psychometric evidence of the presence or absence of capacity, or
      competence. Concern has long been expressed over the variability of these
      assessments. A survey of 285 decisions of the Queensland Guardianship and
      Assessment Tribunal (GAAT) between 2005 and 2008 was conducted to estimate the
      incidence of disagreement between health professionals in capacity assessments;
      to provide examples of conflicting assessments and models of assessment used; and
      to consider the educational implications of disagreements. While the final
      capacity determinations by the GAAT appear sound, this case series, and other
      studies in the capacity literature, strongly suggest the need to improve the
      education of health professionals, especially doctors, at undergraduate and
      postgraduate levels, in the practical assessment of capacity as a fundamental
      clinical skill.

PMID- 18807793
TI  - Selim v Lele and the civil (industrial) conscription prohibition: constitutional
      protection against federal legislation controlling or privatising Australian
      public hospitals.
AB  - Selim v Lele (2008) 167 FCR 61; [2008] FCAFC 13 was a decision of the Federal
      Court which interpreted s 51(xxiiiA) of the Australian Constitution. This section
      accords the federal government, among other things, power to make laws with
      respect to the provision of "medical and dental services (but not so as to
      authorise any form of civil conscription)". The Federal Court decided that the
      phrase "civil conscription" was analogous to "industrial conscription". In that
      sense the Federal Court held that the prohibition was designed to preserve the
      employment autonomy of Australian medical practitioners or dentists, preventing
      federal laws that required them, either expressly or by practical compulsion, to
      work for the federal government or any industrial employer nominated or permitted
      by the federal government. The specific question in Selim v Lele was whether the
      imposition of standards and prohibition of "inappropriate practice" under the
      Health Insurance Act 1973 (Cth), ss 10, 20, 20A and Pt VAA, amounted to civil
      conscription. The court held they did not. The Federal Court also discussed in
      that context the sufficiency of "practical compulsion" in relation to the s
      51(xxxiiiA) prohibition, The constitutional prohibition on "any form" of civil
      conscription provides one of the few rights protections in the Australian
      Constitution and may have an important role to play in shaping the limits of
      health care system privatisation in Australia.

PMID- 18807794
TI  - UNCROC and the prevention of childhood obesity: the right not to have food
      advertisements on television.
AB  - This article discusses how legal rights-based discourse could inform the response
      of Australian State and federal governments to the increasing prevalence of
      childhood obesity. The authors contend that the principles in the United Nations
      Convention on the Rights of the Child (a treaty which has been ratified but not
      implemented) are capable of providing a basis for a legislative program to
      prevent childhood obesity. It is argued that an approach to legislation which is
      grounded on the basis of children's rights would require that there be
      restrictions on advertising food to children. The authors set out specific
      proposals for legislative reforms which the federal Parliament could enact to
      implement the Convention so as to restrict advertising to children. The scope of
      the discussion is then expanded to consider the implications of rights-based
      discourse in broader public health contexts.

PMID- 18807795
TI  - Public expectations of health professionals when patients telephone for medical
      advice.
AB  - This article focuses on the ethical, social and liability implications of
      patients obtaining unsolicited medical advice over the phone. The ethical
      discussion centres on the demise of paternalism and the increase in patient
      autonomy and individualism and the growing public expectations of health
      professionals. The article then discusses the advantages and disadvantages of
      telephone consultations from a social and policy perspective. In light of these
      considerations it considers what the liability implications are for phone
      consultations. It argues that the ethic of individualism, coupled with recent
      Australian tort reforms, suggests that only in limited circumstances would a
      doctor be found liable for negligence in relation to telephone consultations.
      However, the increasing expectations being placed on medical personnel, as
      evidenced by the increase in unsolicited telephone consultations, if left
      untempered, may lead to a situation with which the health care system is ill
      equipped to deal.

PMID- 18807796
TI  - End-of-life decision-making, the principle of double effect, and the devil's
      choice: a response to Roger Magnusson.
AB  - Recently, the principle of double effect has come under scrutiny by Magnusson who
      believes it provides a subterfuge for those who act so as to end the lives of
      their patients. Specifically, he argues that the conceptual distinction between
      foresight and intention is dubious and, moreover, renders patients vulnerable to
      involuntary euthanasia. At the same time, Magnusson wants to protect doctors from
      criminal liability when faced with (what he understands to be) a "devil's choice"
      between ending the life of a patient or under-treating pain. Hence, Magnusson
      proposes that, subject to specific conditions, a so-called "defence of necessity"
      be recognised through either common law doctrine or legislation. However, to
      safeguard this defence, he must rely on what he most wants to reject: a
      fundamental aspect of the principle of double effect.

PMID- 18807797
TI  - The Human Rights Review Tribunal and the rights of health and disability
      consumers in New Zealand.
AB  - In New Zealand where there is a statutory bar on the right to sue for
      compensatory damages arising out of personal injury, and therefore injury arising
      out of negligent health care, the Human Rights Review Tribunal, in certain
      circumstances, provides relief for people who are aggrieved by the care they have
      received from a provider of a health or disability service. That relief may range
      from a declaration that the provider has breached the Code of Health and
      Disability Services Consumers' Rights to awards of compensatory and exemplary
      damages. The article explores the use of this tribunal by the Director of
      Proceedings of the Office of the Health and Disability Commissioner in holding
      providers of health and disability services accountable and obtaining relief for
      consumers and their families.

PMID- 18807798
TI  - Herceptin, Pharmac and the New Zealand District Health Boards: keeping abreast of
      the Code of Health and Disability Services Consumers' Rights?
AB  - In an era of resource limitations, the problem of matching public expectations
      with health care provision will always be difficult. In New Zealand there has
      been recent debate surrounding the potential funding by the Pharmaceutical
      Management Agency (PHARMAC) of an expensive chemotherapy agent called Herceptin
      (trastuzumab). Taking the proposed funding options in turn, this article looks at
      the obligations PHARMAC and the New Zealand District Health Boards might then be
      subject to with respect to the legislation and the Code of Health and Disability
      Services Consumers' Rights, and the impact this might have on a health system
      already subject to resource constraints.

PMID- 18807799
TI  - Developments in pharmacists' disciplinary processes and outcomes.
AB  - Pharmacy disciplinary processes and outcomes protect consumers by deterring
      pharmacists from unacceptable practices and maintaining the reputation and
      standing of the pharmacy profession. It is important that pharmacists are
      informed of disciplinary processes and outcomes in order to predict what is
      regarded as unacceptable behaviour and the potential consequences thereof.
      Disciplinary procedures and outcomes also play an important role in maintaining
      public trust in the pharmacy profession and it is therefore important that the
      public has confidence in the disciplinary structure. The outcomes of pharmacy
      disciplinary cases that reflect the patient care role of pharmacists are
      particularly important in helping to determine pharmacists' changed professional
      responsibility and potential legal liability in the provision of these patient
      care services.

PMID- 18807800
TI  - Reviewing regulation of assisted reproductive technology in New South Wales: the
      Assisted Reproductive Technology Act 2007 (NSW).
AB  - In November 2007, the Assisted Reproductive Technology Act 2007 (NSW) was passed
      to deal with a number of issues under the spectrum of reproductive technologies.
      The legislation was the outcome of a review conducted by the New South Wales
      Health Department and adopts a different approach to other Australian statutory
      regulation. This article considers the approach of the new legislation and
      whether there are some issues that require further consideration under the new
      regulatory regime. In particular, discussion is focused on the failure of the new
      legislation to address eligibility for reproductive treatments as well as the use
      of pre-implantation genetic diagnosis for the creation of tissue-matched
      children.

PMID- 18807801
TI  - The Lockhart Committee: developing policy through commitment to moral values,
      community and democratic processes.
AB  - The Lockhart Committee was appointed by the federal government in 2005 to review
      the Prohibition of Human Cloning Act 2002 (Cth) and the Research Involving Human
      Embryos Act 2002 (Cth). The issues in the review are ones on which community
      views differ widely and many people hold strong and diverging opinions. Yet all
      members of the committee were able to agree on their recommendations when the
      committee reported to Parliament in December 2005 and since that time, most of
      its recommendations have been implemented in amendments to federal and State
      legislation. This article describes the committee's process in considering the
      issues in the review, in consulting stakeholders and the broader community and in
      formulating its recommendations.

PMID- 18807802
TI  - Therapeutic cloning in Australia: one small stem from man, one giant leap for
      mankind.
AB  - In 2002 the Australian Parliament enacted legislation which prohibited both
      therapeutic and reproductive embryonic cloning. Just four years later, in
      December 2006, this same legislation was amended, reversing the prohibition on
      therapeutic cloning, while retaining the ban on reproductive cloning. The Prime
      Minister, sensing the political mood, allowed a conscience vote. This contrasted
      with his decision several months earlier against introducing any changes to the
      2002 Act, despite 54 recommendations having been made by a Statutory Review
      Committee. Approval of the legislation had as much to do with the careful
      drafting of the provisions as with any rational, social or scientific factor. The
      legislation is narrow in scope, retains an absolute prohibition on reproductive
      cloning and contains strict regulations with heavy criminal penalties. The Act
      requires a review after three years. A number of questions remain. Does stem cell
      research demand a global rather than a local approach, by way of an international
      Covenant? Does the legal status of a cloned embryo need further examination? Will
      the embryo have a separate legal standing recognised by law? These are some of
      the questions which will need addressing as the law tries to keep up with
      science.

PMID- 18807803
TI  - Reconstructing the hymen: mutilation or restoration?
AB  - Female genital mutilation (FGM)--previously known as female circumcision--was
      criminalised in many countries in the 1990s. This occurred mainly in Western
      nations and responded to the perception that FGM was intended to subjugate women
      and was an abuse of human rights. However, other female genital surgical
      procedures have a totally different intent and are designed to restore the
      integrity of the hymen, correct deformity or simply enhance the appearance of the
      female genitalia. Such procedures, unlike FGM, are performed on women who have
      reached the age of consent and who request the surgery themselves. Restoring the
      integrity of the hymen (so-called "hymenoplasty") can erase evidence of the
      sexual history of a woman. "Revirgination" may have particular importance to
      women contemplating marriage in cultures where a high value is placed on
      virginity Some commentators have equated hymenoplasty with corrective surgery
      intended to restore the condition of female circumcision--techniques which are
      prohibited by most Australian criminal statutes. However, the medical, ethical
      and human rights arguments against FGM are not easily extended to revirgination
      and other cosmetic genital surgery. This article examines whether revirgination
      surgery has effectively been criminalised in Australia and whether this is
      appropriate from a medical and ethical perspective.

PMID- 18807804
TI  - The consequences of a low autopsy rate.

PMID- 18807805
TI  - Universal neonatal screening; falling on deaf ears?

PMID- 18807806
TI  - Some aspects of neuropathology in central nervous system disease diagnosis.

PMID- 18807807
TI  - Alcohol--how much is too much?
AB  - The aims of this study were to examine perceptions of what a sample of students
      and graduates consider an excessive alcohol intake to be and it's effect on their
      health. 115 University College Cork (UCC) students and 133 UCC graduates were
      questioned about their opinions of an acceptable weekly intake of alcohol. The
      results reveal dramatic changes in drinking habits over recent decades. Students
      began drinking earlier than graduates and are far more accepting of greater
      amounts of alcohol being consumed. The student's average opinion of what
      constituted an excessive weekly alcohol intake was 26.5 units of alcohol/week
      whereas the graduates felt over 18 units/week was too much. We concluded that
      even amongst these highly educated cohorts there is a low level of awareness of
      safe limits of alcohol consumption.

PMID- 18807808
TI  - Can pre-assessment of patients with LUTS result in early discharge from urology
      clinic?
AB  - Waiting times for appointments for urological out-patients in Ireland and the
      U.K. can be excessively long. Nurse-led Lower Urinary Tract symptom (LUTs) pre
      assessment clinics have been introduced to streamline patient care pathways. We
      examined whether a nurse-led pre-assessment LUTS clinic could result in the rapid
      assessment and discharge of patients following their first out-patient visit. A
      pilot study was undertaken whereby patients referred with LUTS were sent for pre
      assessment prior to their out-patients appointment. 214 consecutive patients
      underwent pre-assessment. Of these, 39 (18%) patients were discharged following
      their first out-patient visit and 27 (13%) patients were discharged after a
      second attendance. A further 35 (16%) patients continued to attend but underwent
      no further investigations or treatment, and possibly should have been discharged
      earlier. Overall 46% of pre-assessed patients could have been discharged early
      from the urology clinic. In conclusion a nurse-led pre-assessment LUTS clinic
      could result in the rapid assessment and discharge of patients following their
      first out-patient visit.

PMID- 18807809
TI  - Timing of birth related to obstetric practice and neonatal outcome.
AB  - Several studies have reported time of birth is associated with differences in
      obstetric practice. We investigated the relationship between timing of birth and
      obstetric and neonatal outcomes, to help plan working patterns under European
      Working Time Directive (EWTD) legislation. This was a retrospective observational
      study undertaken in a tertiary-level university teaching hospital. Data were
      derived from the labour ward register of births for all women who delivered after
      24weeks gestation in 2004. Births during on-call hours refer to those that
      occurred at weekends and after 1630 and before 0830 on weekdays. The majority of
      infants, 67.3%, were born in on-call hours. Infants were more likely to be
      delivered by ventouse(p<0.0001), but there was no difference in caesarean
      section(CS) rates. 83.0% of operative deliveries performed for failure to advance
      in the second stage of labour took place in on-call hours, as did 77.5% of
      emergency CS for fetal distress. 38.9% of infants born during on-call hours on
      weekdays followed induced labours, compared to 24.7% of births at weekends and
      17.7% of births in non on-call hours(p<0.001), while 80.0% of deliveries by
      emergency CS after induction occurred during on-call hours. The majority of
      perinatal deaths occurred among infants born during on-call hours, even when
      excluding congenital malformations, and most infants with low Apgar scores were
      born during on-call hours. Complicated deliveries were more likely to occur in on
      call hours. This study confirms previous reports that time of birth impacts on
      neonatal outcome. Increased demands on staff working out-of-hours have
      implications for healthcare, staffing and implementation of new working hours
      under EWTD legislation.

PMID- 18807810
TI  - Chronic musculoskeletal pain and arthritis: impact, attitudes and perceptions.
AB  - The aim of this study was to assess the prevalence, management and impact on
      quality of life of chronic musculoskeletal pain in Ireland by comparing the
      attitudes and perceptions of sufferers to those of general practice doctors
      (GPs). A telephone survey was conducted with 498 people with chronic
      musculoskeletal pain (screened from a total of 3323) and 150 GPs selected
      randomly from the medical register. The survey was based on a structured
      questionnaire that asked about the impact of CMP, usual management and perceived
      benefits and risks of treatment. Chronic musculoskeletal pain, including
      arthritis, affected one in six of the people screened for the survey. 25% of
      those surveyed have never consulted a doctor about their condition and many
      others will have waited up to two years before seeking help. 67% of respondents
      reported that pain caused significant reduction in their quality of life
      (measured using the SF-12 scale). The survey also indicated that people with
      chronic musculoskeletal pain have misconceptions about their condition, treatment
      options and side effects and patients rarely receive written information from
      their GP on these subjects. Chronic musculoskeletal pain, including arthritis is
      common and significantly reduces quality of life in Ireland. People delay seeking
      medical help, despite being in constant/daily pain. Written information is sparse
      and misperceptions relating to treatment are common. Improved awareness and valid
      information may lead to better care for people suffering from CMP in Ireland.

PMID- 18807811
TI  - Dress and address: patient preferences regarding doctor's style of dress and
      patient interaction.
AB  - We sought to determine patient preferences regarding doctor's dress styles and
      mode of doctors introducing themselves to patients and addressing patients. A
      survey of patients attending a general medical/endocrinology outpatient clinic in
      a tertiary referral hospital over a 6 week period was performed. 124 people
      completed the survey (62 male, 62 female). Mean age was 52.3 years (Range 19-84).
      Patients preferred to be addressed by their first name while they prefer doctors
      to introduce themselves by their first and last name. However the majority of
      patients found all forms of doctors introducing themselves acceptable. Patients
      preferred formal attire for both male and female doctors, with a white coat being
      the most preferred option. 84.5% of patients felt that doctors should wear name
      badges in a clearly visible place although only 26% of patients saw name badges
      always or almost always during a consultation. This study raises important points
      regarding the doctor patient interaction.

PMID- 18807812
TI  - Cost induced by hip fractures.
AB  - Hip fracture is the most common fracture in the elderly population. Treating hip
      fractures is a major burden on the Irish Health system. There is no recent
      Republic of Ireland study detailing hospital costs for such injuries. A
      comprehensive analysis of 143 patients admitted with a hip fracture was performed
      to determine current medical expenditure incurred during acute hospitalization
      for hip fractures during 2005 in a major university hospital. Costs associated
      with surgery (implant & theatre costs), laboratory, radiology, physiotherapy and
      ward were calculated on individual basis. All the hip fractures were above 60
      years of age (mean 82 years); average stay in the hospital was 11 days. The mean
      total hospital expenditure per patient was Euro 9236.01 of which ward costs
      contributed 55.33%, operative costs 39.82% and investigations 4.83%. The result
      clearly show that hip fractures have a major economic impact arising from the
      inpatient treatment, most of which relate to length of hospital stay.

PMID- 18807813
TI  - Assessment of the value of pelvic ultrasonography in pre-menopausal women with
      right iliac fossa pain.
AB  - The aim of this study was to determine whether ultrasound examination performed
      in the acute setting can avoid the need for diagnostic laparoscopy in pre
      menopausal women presenting with right iliac fossa pain in whom the diagnosis of
      acute appendicitis is suspected. All female patients aged fifty or under, who
      presented to the Emergency Department with right iliac fossa pain over an
      eighteen-month period, and who went on to have a diagnostic laparoscopy
      performed, were included in the study. Ultrasound and operative findings were
      recorded. 147 patients fulfilling the study criteria were identified. 38 (26%)
      had pre-operative ultrasound performed. 15 of these had normal findings, 10 had
      gynaecological pathology identified, 8 had non-specific findings. Of the 38
      patients who had pelvic ultrasound pre-operatively, 26 (68%) had acute
      appendicitis at laparoscopy, only 5 of whom had a sonographic diagnosis of acute
      appendicitis made pre-operatively. We conclude that while positive ultrasound
      findings in cases of acute appendicitis are helpful, negative studies do not
      exclude the diagnosis. Patients in whom there is a strong clinical suspicion of
      acute appendicitis should proceed directly to laparoscopy while patients in whom
      the diagnosis is less certain, should be admitted for a period of observation
      facilitating repeated clinical evaluation. In this subgroup of patients, further
      imaging studies such as computed tomography may be indicated.

PMID- 18807814
TI  - Day of surgery admission--is this safe practise?
AB  - Day of surgery admission (DOSA) describes the process whereby patients are
      admitted to hospital and have surgery, on the same day. This is the current
      admission policy in our institution, for most elective Otolaryngology Head and
      Neck Surgery patients. We audited 75 consecutive patients admitted on the same
      day as surgery within our department between May 2006 and January 2007.
      Significant comorbidity was seen in 28 patients (37.3%). Preoperative
      investigations prior to surgery were conducted in 64 patients (85.3%). About 21
      patients (28%) were delayed going to theatre and the average length of delay was
      51 mins. Our cancellation rate was 5.3%. Hospital management have embraced the
      concept of DOSA in our institution without evaluating the risk to patients. If
      the DOSA policy is to continue it is imperative that an adequate preoperative
      assessment clinic is established to prevent negative outcomes for our patients.

PMID- 18807815
TI  - Susceptibility of pregnant women to toxoplasma infection--potential benefits for
      newborn screening.
AB  - Congenital toxoplasmosis (CT) arises as a result of new acquisition of Toxoplasma
      infection by a susceptible woman during pregnancy. Early detection of CT through
      neonatal screening programmes could optimize management and improve infant
      outcome. This study sought to estimate the prevalence of Toxoplasma
      susceptibility in pregnant women. As detection of Toxoplasma antibodies in
      neonatal blood reflects maternal exposure history, maternal antibody
      seroprevalence was determined using anonymized residual blood from newborn
      screening cards. A total of 20,252 cards were tested in 1 year. 4,991 (24.6%)
      cards tested positive for Toxoplasma antibody. Results were stratified by county.
      Toxoplasma antibody seroprevalence rates of 25% indicated that Toxoplasma
      infection is common in Ireland and that up to 75% of women remain susceptible to
      primary infection during pregnancy. This study aimed to a) determine the
      seroprevalence of Toxoplasma antibody in pregnant women, and hence b) estimate
      the risk for acquisition of primary toxoplasmosis in pregnancy in order to
      support an application to fund a pilot newborn screening programme.

PMID- 18807816
TI  - The impact of legislation in Ireland on handheld mobile phone use by drivers.
AB  - Under the Road Traffic Act, 2006 handheld mobile phone use whilst driving is an
      offence liable to a fine and penalty points. The aim of this study was to
      determine whether there has been a change in driver behaviour following the
      introduction of this legislation. This study found that 2.3% of drivers were
      still using a handheld mobile phone.

PMID- 18807817
TI  - Polymyalgia rheumatic (PMR): giant cell arteritis (GCA).

PMID- 18807818
TI  - The concept of quality control in medicine: Emedicine.ie and the mobile phone.

PMID- 18807819
TI  - Assessing emergency response training needs of local environmental health
      professionals.
AB  - The Michigan Center for Public Health Preparedness collaborated with
      environmental health (EH) professionals at the local, state, and national levels
      to develop and conduct a state-wide study to identify the preparedness-training
      needs of local EH professionals in Michigan. The specific aims of the study were
      first, to determine the self-rated level of confidence among Michigan's EH
      professionals regarding relevant emergency planning and response competencies;
      second, to determine the specific preparedness training topic preferences of
      Michigan's EH professionals; and third, to establish baseline needs assessment
      data to be used to track progress toward higher levels of readiness after
      implementation of planning, training, and other preparedness activities. The
      study recruited 400 EH professionals to complete the survey (61% of all EH
      professionals in 45 local health departments in Michigan). The top training topic
      preferences were "environmental health role in emergencies" followed by "water
      security" and "food security." The EH professionals rated their confidence in
      demonstrating relevant emergency planning and response competencies. Most of the
      average ratings (on a 5-point scale) were close to the scale's middle point
      (rating = 3), suggesting that EH professionals rate themselves as "somewhat
      confident" in performing important tasks in preparedness and response. Variations
      in specific ratings helped identify training needs. The discussion of these
      results focused on the implications of this study for the development of
      emergency response training for environmental health professionals.

PMID- 18807820
TI  - Cryptosporidiosis outbreak in a Nassau County, Florida, return travel group from
      Ireland, May 24, 2006-June 4, 2006.
AB  - The Nassau County Health Department (NCHD) in Florida investigated an outbreak of
      gastrointestinal (GI) illness in a returning choral group who toured Ireland from
      May 24 to June 4, 2006. The travel group, consisting predominantly of retirees,
      had performed at several churches and at a dinner theater in Ireland. The NCHD
      administered a telephone questionnaire to 40 of the 41 group members to examine
      possible water exposures; common meals; and food, travel, and clinical histories.
      The results of the questionnaire showed that 29 people met the case definition
      for the outbreak. Five stool samples from travel group members tested positive
      for Cryptosporidium parvum, a species that is animal in origin and often spread
      through an environmental contamination with animal feces. All five positive
      samples were subtyped 11aA16G1R1b, a strain that scientists at the Centers for
      Disease Control and Prevention (CDC) Division of Parasitic Diseases detected
      twice in 2006 in other human specimens from Northern Ireland.

PMID- 18807821
TI  - Making it work: the application of time as a public health control in the field.
AB  - Time as a public health control (TPHC) is increasingly being recognized as a
      viable alternative to temperature control for potentially hazardous foods in the
      developed world. This is reflected by recent changes to food regulations and
      other pertinent health legislation in both Canada and abroad. Considerable
      ambiguity remains, however, as to when and how TPHC should be applied at the
      field level. The author reviewed pertinent legislation, regional standards, and
      guidelines in various jurisdictions. The author did not identify standardized
      methods for having health departments receive applications from food vendors, for
      evaluating such applications for approval or rejection once received, or for
      monitoring food products subsequent to such an approval. A 4-step process was
      then designed to help ensure a standardized application of TPHC principles at the
      field level. Applications, representing a variety of potentially hazardous food
      products from both ethnic and North American cuisines, were reviewed and
      processed according to stated criteria. A structured format for the application,
      approval, monitoring, and evaluation of potentially hazardous ready-to-eat foods
      by management and field personnel helps improve consistency in the application of
      TPHC principles, demonstrate due diligence (for environmental public health
      departments), and relieve district environmental health officers (EHOs) from the
      pressures of having sole responsibility over the approval process.

PMID- 18807822
TI  - The role of environmental health in disaster management: a qualitative study of
      Australian experiences.
AB  - Even though environmental health is widely considered to be an integral component
      of disaster management, limited research on this topic has been conducted. Using
      a qualitative approach, the authors conducted in-depth interviews of
      practitioners in Queensland, Australia, to explore the role of environmental
      health in disaster management and determine how those internal and external to
      the profession perceive this role. The major themes that emerged described a
      process in which the "view of health" is socially constructed, and this process
      is instrumental in shaping perception of the environmental health role in
      disaster management. The authors also found that the role of environmental health
      in disaster management is experiencing renegotiation due to a complex process of
      challenging the socially constructed view of health, raising the profile of the
      profession, and achieving increased representation in disaster management.
      Ultimately, increased recognition and a heightened profile of environmental
      health will result in a more effective disaster management system and will carry
      over into day-to-day activities.

PMID- 18807823
TI  - Relationship between particulate matter measured by optical particle counter and
      mortality in Seoul, Korea, during 2001.
AB  - This study was performed to examine the relationship between particulate matter
      exposure and mortality in Seoul, Korea, during the year 2001. Particulate matter
      data were collected using an optical particle counter (OPC) and national
      monitoring stations in Seoul. The size-resolved aerosol number concentrations of
      particles 0.3-25 microm in diameter and mass concentrations of PM10 (particulate
      matter less than 10 microm in diameter) and PM2.5 (less than 2.5 microm in
      diameter) were measured. Meteorological data such as air temperature and relative
      humidity were provided by the Korea Meteorological Administration. Daily
      mortality was analyzed using a generalized additive Poisson model, with
      adjustment for the effects of seasonal trend, air temperature, humidity, and day
      of the week as confounders, in a nonparametric approach. We used S-Plus for all
      analyses. Model fitness, using loess smoothing, was based on stringent
      convergence criteria to minimize the default convergence criteria in the S-Plus
      generalized additive models module. The IQR (interquartile range) increase of
      fine particle (10.21 number/cm3 [the total number of particles per cubic
      centimeter]) and respiratory particle (10.38 number/cm3) number concentration
      were associated with a 5.73% (5.03%-6.45%) and a 5.82% (5.13%-6.53%) increase in
      respiratory disease-associated mortality, respectively. Mortality effects in the
      elderly (aged over 65 years) were increased by more than 0.51% to 2.59%, and the
      relative risks of respiratory-related and cardiovascular-related mortality were
      increased by 0.51% to 1.06% compared with all-cause mortality. These findings
      support the hypothesis that air pollution is harmful to sensitive subjects, such
      as the elderly, and has a greater effect on respiratory- and cardiovascular
      related mortality than all-cause mortality. However, our results using OPC data
      did not support the hypothesis that PM2.5 would have more adverse health effects
      than PM10 in number concentration but not in mass concentration.

PMID- 18807824
TI  - Behavioral science and food safety.

PMID- 18807825
TI  - Construction and demolition (C&D) landfills: emerging public and occupational
      health issues.

PMID- 18807826
TI  - The Alamosa Salmonella outbreak: a gumshoe investigation.

PMID- 18807827
TI  - It pays to treat sleep apnea.

PMID- 18807828
TI  - The art of resolving conflicts.

PMID- 18807829
TI  - Developing next-level leadership power.

PMID- 18807830
TI  - Point and click.

PMID- 18807831
TI  - Lockout basics.

PMID- 18807832
TI  - How to use the 'minor service exception'.

PMID- 18807833
TI  - Back to the basics.

PMID- 18807834
TI  - The softer side of safety.

PMID- 18807835
TI  - Bad assumptions about hearing protection.

PMID- 18807836
TI  - Noise in the workplace and hearing loss.

PMID- 18807837
TI  - All eyes on the prize.

PMID- 18807838
TI  - Managing the risks of a defective product.

PMID- 18807839
TI  - Hazards demand proper protection.

PMID- 18807840
TI  - Toward a healthier bottom line.

PMID- 18807841
TI  - Case study: Office Depot makes motivation meaningful.

PMID- 18807842
TI  - Running the risk of poor IAQ.

PMID- 18807843
TI  - Monitoring indoor CO2.

PMID- 18807844
TI  - Controlling diacetyl exposures.

PMID- 18807845
TI  - Virtual preparedness.

PMID- 18807846
TI  - Total performance safety.

PMID- 18807847
TI  - Curbing forklift impacts.

PMID- 18807848
TI  - The psychology of work.

PMID- 18807849
TI  - Pay attention!

PMID- 18807850
TI  - Updating motor carrier compliance, part II.

PMID- 18807851
TI  - Delivering safety.

PMID- 18807852
TI  - Going with the flow.

PMID- 18807853
TI  - Using simulated education for real learning.

PMID- 18807854
TI  - Parting shots: conversations in research with clinicians.

PMID- 18807855
TI  - Evidence-based practice: a falls prevention program that continues to work.
AB  - The successful implementation of an evidence-based falls prevention protocol in
      an acute care facility is described. The number of falls per 1000 patient days
      decreased by 50% without rebound over a 5-year period.

PMID- 18807856
TI  - The Internet: can patients link to credible resources?
AB  - With the large number of Internet sources available for health care information,
      finding appropriate sources can be difficult for patients. Medical-surgical
      nurses can guide patients to credible sites with reliable information about
      specific conditions, such as chronic obstructive pulmonary disease. Suggestions
      for evaluation of health care sites are included.

PMID- 18807857
TI  - Are we on the same page?: a comparison of intramuscular injection explanations in
      nursing fundamental texts.
AB  - The researchers investigated issues related to teaching student nurses to
      administer intramuscular (IM) injections. Appropriate site selection and
      location, and issues related to common procedures associated with IM injections
      (z-track and bubble techniques) are explored.

PMID- 18807858
TI  - A primer in the evaluation of quality in acute care settings.
AB  - Nurses are in a unique position to evaluate acute care quality. The authors
      describe common problems and challenges related to selection of variables and
      choice of databases for quality evaluations. Practical strategies to address
      these concerns also are discussed.

PMID- 18807859
TI  - A prospective descriptive study exploring hope, spiritual well-being, and quality
      of life in hospitalized patients.
AB  - A study evaluating relationships among interventions and outcomes of hope,
      spiritual well-being, quality of life and length of stay in hospitalized patients
      at admission, discharge, and 6 weeks after discharge is described. The findings
      highlight the importance of presence, listening; and other caring behaviors in
      the patient experience.

PMID- 18807860
TI  - Measuring constructs.

PMID- 18807862
TI  - An overview of prostate cancer: diagnosis and treatment.

PMID- 18807861
TI  - Using interdisciplinary shared governance and patient rounds to increase patient
      safety.

PMID- 18807863
TI  - Whistleblowing: role of organizational culture in prevention and management.

PMID- 18807864
TI  - Arterial blood gases.

PMID- 18807865
TI  - Heart failure.

PMID- 18807866
TI  - A military twist to the profession of nursing.

PMID- 18807867
TI  - [The characteristics of the development of rural families morbidity].
AB  - The morbidity of mothers and fathers residing in the full, involved and
      incomplete rural families is analyzed. The gender and inter-type rural family
      differences in the disease rate are established. The characteristics of the
      formation of the age-related structure of morbidity among the fathers and mothers
      as the major causes of death among the rural population are determined.

PMID- 18807868
TI  - [The morbidity of physicians of pre-pensionary age].
AB  - The data research related to the investigation of the morbidity of the physicians
      of pre-pensionary age on the basis of medical check-up results. It is established
      that more than 95% of physicians suffered from chronic diseases. At that most of
      them had several diseases. Among the examined groups of physicians according
      their gender, age and duration of work in the medicine the most morbid were the
      physicians older than 50 years and with the period of probation 25 years and
      more. In the structure of the revealed pathology leading role was played by the
      cardiovascular diseases, the diseases of musculo-skeletal system, the diseases of
      the eye and its supplementary apparatus, the respiratory diseases and the
      diseases of urogenital system. The revealed characteristics of morbidity are to
      be taken into account at the development of the group and individual programs of
      preservation, rehabilitation and promotion of physicians' health.

PMID- 18807869
TI  - [The adaptation potential of student youth].
AB  - The research data concerning the social psychological adaptation of student youth
      to the general social conditions and the immediate vitality environment is
      discussed. The University entrance is characterized by changing of activities and
      hence intensifying of the adaptation processes. The students experience higher
      psychological physiological stress factually of all body systems. It results in
      the development of chronic non-infectious diseases among future specialists. On
      the basis on the analysis of positive-negative assessment by the students of
      major aspects of their life and the level of being satisfied with occurring
      social changes it was established that only 28,1% of students managed to fit into
      the new social environment and to adapt to the conditions of modern life.

PMID- 18807870
TI  - [The morbidity of stomach cancer among the workers of key industries of the
      Kuznetsk Basin (Kuzbas)].
AB  - The data research of the retrospective analysis of the morbidity of stomach
      cancer in the Kirov oblast (1990-2005) is presented. The dependence of morbidity
      rate from the volume production and processing of coal is established. The
      forecasting of morbidity rate of stomach cancer is estimated up to 2013
      considering the factual indicators of volume of output in the key industries of
      Kuzbas.

PMID- 18807871
TI  - [On the polypathias in males].
AB  - The structure and prevalence of polypatias (i.e. three and more diseases in
      single person), their qualitative and quantitative characteristics were
      investigated on the basis of comprehensive population study of 1050 males aged
      from 18 and older in unorganized rural population. It is established that in the
      structure of chronic infectious diseases the share of persons with multinozoology
      constituted 65.3%? with binozoology--18% and with mononozoology--16.7%. The
      prevalence level of multinozoology among males constituted 604.7 per thousand?
      binozoology--166.8 per thousand and mononozoology--154.4 per thousand. The
      leading positions among multinozoologies are taken by the circulatory system
      diseases (428.0 per thousand), respiratory system diseases (400.4 per thousand)
      and digestive system diseases (368.9 per thousand). This fact proves the leading
      role of the diseases of those classes in the development of polypatias.

PMID- 18807872
TI  - [The implementation of the automated information systems in health management of
      regional level].
AB  - In public health, the problem of professional community staff disbalance is
      rather critical and the training of medical professional personnel is deficient.
      The decisive role in the solution of the mentioned problems belongs to the
      automated information systems and computer-based technologies. In the
      Nijegorodskaya oblast, the accessible and effective system of training executive
      personnel reserve is developed and implemented to strategically develop the
      executive mangers potential and to enhance the effectiveness of functioning of
      the curative preventive institutions.

PMID- 18807873
TI  - [On the issue of the implementation of the preventive activities in the
      functioning of medical sanitary units].

PMID- 18807874
TI  - [On the issue of the development of municipal public health system].
AB  - The municipal public health is the basic sector of the actual health care system
      functioning in the Russian Federation nowadays. The research data from the
      Sverdlovskaya oblast revealed that today for the region development process was
      characterized by marked disproportions in the state of population health of
      municipal formations, in the local health care resources and in the effectiveness
      of their use. The implementation of multi-factorial analysis permitted to reveal
      the significant impact of public health on the development of the medical
      demographic situation in the municipal formations. Various choices of optimizing
      the public health management in the regions are discussed.

PMID- 18807875
TI  - [The actual problems of the professional personnel supply for regional public
      health].

PMID- 18807876
TI  - [The coming into being and evolution of the system of emergency medical care in
      Russian cities in XIX-early XX centuries].

PMID- 18807877
TI  - [The medical care of ethnos and the preservation of folk medicine in the system
      of life-support of population of the Middle Volga region].

PMID- 18807878
TI  - [The historical aspects of the antituberculous service activities in the Irkutsk
      oblast].

PMID- 18807879
TI  - [The contribution of V. I. Grebenschikov in the evolution of the sanitary and
      demographic statistics].

PMID- 18807880
TI  - [Future of child neurology--child neurologists should speak up].

PMID- 18807881
TI  - [Behavioral abnormality in a 10-years-old boy with Addison disease].

PMID- 18807882
TI  - [Neurological diseases in childhood and cytokines].
AB  - Immune and inflammatory responses are related to the pathogenesis of various
      diseases, including neurological diseases in childhood. Cytokines modify the
      pathogenesis of these diseases. Analyses of cytokines and transcription factor NF
      kappa B activation in patients with acute encephalitis, bacterial meningitis,
      tracheostomy and profound multiple disabilities, and neonatal asphyxia were
      described. It is important for the diagnosis and treatment of diseases to
      understand their pathogenesis and severity by analyzing cytokines and NF-kappa B
      activation.

PMID- 18807883
TI  - [Attempt for development of rapid word reading test for children--evaluation of
      reliability and validity].
AB  - We developed a rapid word reading test for examining the phonological processing
      ability of Japanese children. We prepared two versions of the test, version A and
      B. Each test has word and non-word tasks. Twenty-two healthy boys of third grade
      in primary schools participated in this validation study. For criterion related
      validity, we performed the serial Hiragana reading test, the sentence reading
      test, Raven's coloured progressive matrices (RCPM), the Token test for children,
      the Kana word dictation test, the standardized comprehension test of abstract
      words (SCTAW), and Trail Circle test. The reading times of the newly developed
      test correlated moderately or highly with those of the serial Hiragana reading
      test and the sentence reading test. However, the scores of the other tests (RCPM,
      Token test for children, Kana word dictation test, SCTAW, Trail Circle test) did
      not correlated with the reading time of the rapid word reading test. Test-retest
      reliabilities in the word tasks were more than moderate: 0.52 and 0.76 in
      versions A and B, while those in the non-word tasks were high: 0.91 and 0.88 in
      versions A and B. The correlation coefficient between versions A and B was 0.7
      for the word tasks and 0.92 for the non-word tasks. This study showed that the
      rapid word reading test has substantial validity and reliability for testing the
      phonological processing ability of Japanese children. In addition, the non-word
      tasks were more suitable for selectively examining the speed of the grapheme to
      phoneme conversion process.

PMID- 18807884
TI  - [Questionnaire survey on sleep habit of 3-year-old children in Asahikawa City].
AB  - The present study surveyed the sleep habits of 3-year-old children in Asahikawa
      city using questionnaires completed by a parent during children's medical check
      ups. Questionnaires were collected from the parents of 404 children (209 males,
      195 females; mean age, 3.1 years) enrolled in this survey. Among these children,
      the mean bedtime was 9.6 PM with 145 children (36%) going to bed after 10 PM. On
      the other hand, the mean wake-up time was 7.5 AM, with 123 children (30%) waking
      up after 8 AM. The mean nocturnal sleep duration was 10.1 hours. Nocturnal sleep
      durations in children that went to bed after 10 PM were significantly shorter
      than in children who went to bed earlier (p < 0.01). Seventy-three percent of the
      children had a daily afternoon nap. Twelve percent of these children usually
      awoke from their nap after 5 PM, and the mean bedtime for these children was 10.1
      PM. A late bedtime was significantly correlated with parental complaints such as
      short-temper and poor appetite (p < 0.05). Although parents were concerned about
      night-time sleep conditions, they were not concerned about the daytime conditions
      which regulate children's sleep-wake rhythm, such as daylight exposure, daytime
      activity, and naps. While 24% of parents had complains regarding their children's
      sleep, only 3% had consulted with a doctor. Similar to the previous reports, the
      present findings demonstrate that children in Asahikawa city go to bed late and
      have decreased sleep duration. Since the establishment of a normal sleep-wake
      rhythm is essential for both physical and mental development in children, it is
      necessary to educate parents regarding the importance of children's sleep.

PMID- 18807885
TI  - [Posterior leukoencephalopathy syndrome in children--clinical and
      neuroradiological findings].
AB  - We reported the clinical and neuroradiological findings of 8 patients (4 males; 4
      females; age range; 3 - 14 years) with posterior leukoencephalopathy syndrome
      (PLES). Previous case reports suggested that one of the major factors leading to
      PLES was severe hypertension. We divided the patients into two groups with or
      without severe hypertension, and each group was divided furthermore into two
      corresponding to the reversibility of brain lesions. The four cases of PLES with
      severe hypertension were all due to renal hypertension, and half of them resulted
      in irreversible outcomes, which were considered to be associated with
      inappropriate treatment. On the other hand, the four cases of PLES without severe
      hypertension showed reversible change, suggesting intravascular endothelial
      dysfuncton in respect of their causing factors. We consider that PLES could be
      caused without sever hypertension, particularly in children. Those with severe
      hypertension must be treated immediately to prevent irreversible brain damage.

PMID- 18807886
TI  - [Immunohistochemical analysis of hepatic steatosis in autopsy cases of severe
      motor and intellectual disabilities].
AB  - To explore the pathogenesis of hepatic steatosis in severe motor and intellectual
      disabilities (SMID), we immunohistochemically examined the accumulation of
      oxidative products in 8 autopsy cases of SMID, 5 of which pathologically showed
      hepatic steatosis. Three of the 8 cases also demonstrated fibrosis in Glisson's
      sheath. Serial sections of liver were treated with monoclonal antibodies to
      oxidative products to proteins, lipids and nucleosides. Immunoreactivity for 4
      hydroxynonenal, a marker of oxidative damage to lipids, was increased in the
      cytoplasm of hepatocytes in 5 cases; 2 with steatosis plus fibrosis, one with
      only fibrosis, and 2 with only hepatic steatosis. One case showed
      immunoreactivity for advanced glycation endproduct, a marker of oxidative damage
      to protein, in hepatocytes. There was no immunoreactivity for 8-hydroxy-2'
      deoxyguanosine and hexanoyl lysine, markers of oxidative damage to DNA and
      lipids, respectively. These findings partly mimic those observed in adult
      patients with nonalcoholic steatohepatitis. The results suggested the involvement
      of oxidative damage to lipids in the pathogenesis of hepatic steatosis and/or
      fibrosis in patients with SMID.

PMID- 18807887
TI  - [Prevalence of cerebral palsy in Okinawa between 1995 and 2001].
AB  - We report a population based study of prevalence of cerebral palsy in children
      born between 1995 and 2001 in Okinawa. The overall prevalence of cerebral palsy
      was 2.3 per 1,000 live-births; this result was higher than that reported in our
      previous study conducted between 1988 and 1994. We found a high prevalence of
      cerebral palsy in children weighing less than 2,500 g, especially in those
      weighing less than 1,500 g at birth. Moreover we found children weighing more
      than 1,800 g or those who had more than 33 weeks of gestation period at birth
      showed a lower risk for cerebral palsy.

PMID- 18807888
TI  - [The effect of prophylactic therapy with valproate sodium and phenobarbital in
      two patients with cyclic vomiting syndrome].
AB  - Cyclic vomiting syndrome (CVS) is a disorder characterized by recurrent,
      stereotypic episodes of incapacitating nausea, vomiting, and other symptoms,
      separated by intervals of comparative wellness. Associated symptoms include
      nausea, abdominal pain, headache, and motion sickness. Recently, CVS was
      categorized as a migraine. Case 1 was a girl aged 4 years and 11 months, who had
      frequent and severe episodes of vomiting since she was 3 years old. The diagnosis
      of CVS was established on the basis of clinical symptoms and laboratory data. Her
      electroencephalogram was normal. Prophylactic therapy using a single drug such as
      amitriptyline, carbamazepine, phenytoin, cyproheptadine, valproate sodium or
      phenobarbital was not effective. However, her recurring vomiting disappeared with
      prophylactic therapy using valproate sodium and phenobarbital. Case 2 was a boy
      aged 10 years and 7 months, who had frequent episodes of vomiting since he was 1
      year and 10 months old. He had been receiving intravenous hyperalimentation
      therapy at home since infancy because of frequent vomiting and failure to thrive.
      His electroencephalogram showed no abnormality. Prophylactic therapy using a
      single drug such as diazepam, phenytoin, valproate sodium or phenobarbital was
      not effective. However, his recurring vomiting disappeared with prophylactic
      therapy using valproate sodium and phenobarbital. There were no adverse effects
      in both patients. The combination therapy with valproate sodium (20 - 26
      mg/kg/day) and phenobarbital (4 - 5 mg/kg/day) was effective as a prophylactic
      therapy in these two patients. The combination therapy with valproate sodium and
      phanobarbital for prophylaxis of vomiting may be helpful in patients with
      intractable CVS.

PMID- 18807889
TI  - [ACTH therapy for infantile spasms with chronic renal failure].
AB  - A one-year-old female patient with infantile spasms who suffered from chronic
      renal failure was treated with ACTH for the control of frequent tonic spasms. She
      received 0.005 mg/kg of ACTH for 7 days and then 0.01 mg/kg for 12 days daily.
      From 12 days after initiation of the treatment, tonic spasms and hypsarrythmia
      observed on electroencephalography disappeared. During the ACTH treatment,
      hypertension and gastric bleeding developed, and persisted even with
      antihypertensive drugs and a H2-blocker treatments. During the ACTH therapy, the
      serum cortisol level was higher than that in control subjects. Recent advances
      regarding the metabolism of cortisol have shown that the inactivation of cortisol
      is impaired in patients with chronic renal failure and that clearance of cortisol
      from serum is decreased in such patients. It is suggested that the same mechanism
      was involved in the present patient during the ACTH therapy and that adverse
      effects of ACTH were related to the high cortisol level in the serum. We conclude
      that the dose and duration of ACTH therapy should be determined by careful
      monitoring for the adverse effects of ACTH, and that the serum cortisol level
      might be a predictor of the side effects of ACTH therapy in a patient with
      chronic renal failure.

PMID- 18807890
TI  - [Outcome assessment in treatment of edaravone in childhood ischemic stroke].

PMID- 18807891
TI  - [A successful new liposteroid therapy for West syndrome in polycystic
      encephalopathy].

PMID- 18807892
TI  - [New frontier in perioperative blood component therapy--preface and comments].
AB  - The latest revision of Japanese practical guidelines for the blood component
      therapy, edited by the Ministry of Health, Labour and Welfare of Japan in 2005,
      consisted of several crucial points including: emergency red cell transfusion for
      critically ill patients; the computer crossmatch; and non-erythrocyte blood
      component therapy based on diagnosis for coagulopathy. The guidelines issued by
      the Japanese Society of Anesthesiologists as well as the Japan Society of
      Transfusion Medicine and Cell Therapy (2008) further focused on the strategy for
      perioperative massive blood loss. Seven feature articles following this opening
      article summarizes the topics for the new frontier in perioperative blood
      component therapy in Japan.

PMID- 18807893
TI  - [Preventive measures against transfusion-associated complications and side
      effects].
AB  - The current efforts and strategies have greatly helped reduce transfusion
      associated risks. Indeed, the risk of being infected by a contaminated blood unit
      today is lower than that thirty years ago. This improvement is due to the
      introduction of nucleic acid testing (NAT). Compatibility testing is designed to
      ensure that the patient receives the intended units of red cell concentrate (RCC)
      and that transfusion will be effective with minimum risk of adverse reactions.
      The process includes ABO and Rh typing of patients, testing recipient serum for
      clinically important alloantibodies, and crossmatching donor red cells with
      recipient serum by a technique that detects serological incompatibility.

PMID- 18807894
TI  - [Monitoring of allogenic red blood cell transfusions].
AB  - Careful assessment of risks and benefits has to precede each decision on
      allogenic red blood cell (RBC) transfusion. Physicians work to establish more
      appropriate transfusions of blood components according to the guidelines issued
      by the Ministry of Health, Welfare, and Labor in Japan. For many years the so
      called "10/ 30 rule" was used as a hemoglobin/hematocrit transfusion trigger.
      However, this rule does not take into account the individual anemia tolerance of
      a patient nor its individual compensatory mechanisms. RBC transfusions should not
      be dictated by a single hemoglobin transfusion trigger, but instead should be on
      the patient's risk of developing complications of inadequate oxygenation.
      Therefore, transfusion decisions should be primarily based on an individual
      patient's need for global and regional oxygen supply as indicated by signs of
      inadequate global and regional oxygenation. However, a hemoglobin transfusion
      trigger may be useful if matched with some other makers of inadequate tissue
      perfusion. Therefore, RBC transfusion is recommended under the following
      circumstances: for hemoglobin levels < 6 g x dl(-1) and for physiologic signs of
      inadequate oxygenation.

PMID- 18807895
TI  - [Diagnosis and transfusion algorithm for the management of perioperative
      coagulopathy].
AB  - The present article reviewed the management of coagulopathy in the perioperative
      setting, following the Japanese practical guidelines for the blood component
      therapy, edited by the Ministry of Health, Labour and Welfare of Japan in 2005.
      The threshold concentrations of platelets, prothrombin time international
      normalized ratio (PT-INR) and activated partial thromboplastin time (APTT) were
      optimized for the perioperative critical care under active and/or microvascular
      bleeding, based on currently available randomized controlled trials.
      Discontinuation or modification of anticoagulants as well as antiplatelets is
      essential for the safe perioperative care. Several factors, including
      normothermia, normovolemia, as well as the maintenance of plasma calcium levels
      within normal range, are important for the management of coagulopathy. Platelet
      counts, PT, APTT, and if possible, other point-of-care testing including
      thromboelastography and its modified techniques should be performed following
      visual inspection of abnormal bleeding. The transfusion algorithms based on
      causal diagnosis of coagulopathy optimize the risk/ benefit ratio of
      perioperative transfusion therapy.

PMID- 18807896
TI  - [Critical massive blood transfusion--O type and variant conformity blood
      transfusion].
AB  - Variant conformity blood is often used in transfusion at massive unpredictable
      hemorrhage under an operation or at hemorrhagic shock in a lifesaving emergency
      arena. This is because of difficulty in performing blood grouping, because of
      difficulty in deciding blood types in the laboratory, or because of lack in store
      of the same blood type transfusion as a pharmaceutical preparation needed for the
      patients. In performing variant conformity transfusion in the hospital, it is
      vitally important that in-house system be well-organized and staff be thoroughly
      informed about variant conformity transfusion. This chapter explains system
      arrangements of organization for variant conformity transfusion in hospital
      settings based on our experience in the urgent use of O type RCC-LR (Red Cells
      Concentrates-Leukocytes Reduce, "Nisseki") pharmaceutical preparation.

PMID- 18807897
TI  - [Risk and crisis management by anesthesiologists regarding 'Guidelines for
      Actions Against Intraoperative Critical Hemorrhage' published by the Japanese
      Society of Anesthesiologists and the Japan Society of Transfusion Medicine and
      Cell Therapy].
AB  - According to a survey of anesthesia-related critical incidents by the Japanese
      Society of Anesthesiologists, hemorrhage was the major cause of cardiac arrest
      developing in the operating room. To deal with critical hemorrhage swiftly, not
      only cooperation between anesthesiologists and surgeons but also the linkage of
      operating rooms with transfusion management divisions and the blood center is
      important. It is desirable for the hospital transfusion committee to prepare
      hospital regulations on 'actions to be taken to manage critical hemorrhage', and
      practice the implementation of these guidelines by simulated drills. When
      critical hemorrhage occurs, a person in charge is appointed, and an emergency is
      declared (call for manpower and notification of the emergency to the transfusion
      management divisions). A person in charge comprehensively assesses the hemostatic
      condition, hemodynamics, laboratory data, and blood product supply system, and
      consults the operator regarding the continuation of surgery or changing surgical
      procedures. When time is short, the cross-matching test is omitted, and the ABO
      identical blood is used. When a supply of the identical ABO-type blood is not
      available, compatible blood type is used. The evolving concept of hemostatic
      resuscitation seems to be important to prevent coagulopathy, which easily
      develops during massive hemorrhage. Anesthesiologists should be aware of the risk
      of such an emergency transfusion and procedures to be taken to switch to
      transfusion of the ABO-identical blood. Establishment of a hospital emergency
      transfusion system depends on the overall capability of the critical and crisis
      management systems of the hospital.

PMID- 18807898
TI  - [New crossmatch procedure: computer crossmatch experience in a blood service
      division].
AB  - We established a computer crossmatch system in our hospital to commence 24-hour-a
      day blood services. About 97% of red blood products were shipped using this
      system. Among them, only one patient developed a mild delayed hemolysis. ABO
      mismatched transfusion or release of incompatible blood components was not
      reported at all. Since the turnaround time is shortened, cost reductions were
      achieved by reductions in blood units tied up in the crossmatched blood
      inventory, leading to reduced blood ordering.

PMID- 18807899
TI  - [Significance of computer crossmatching in anesthesiology].
AB  - We introduced a computer crossmatching system into our institution in June 2002.
      This method gives a great advantage for anesthesiologists by being able to
      provide adequate blood within five minutes after ordering using this system. We
      have adapted all cases for transfusion (around 97% of all transfusions),
      including not only scheduled but also emergent cases to the system in our
      institution. We have experienced no clinical problems by the introduction of the
      system from 2002 to 2007. Because the system provides many advantages for various
      related aspects, for example, decreasing blood disposal and labor saving for
      laboratory technicians, we expect that the system will be used widely.

PMID- 18807900
TI  - [Comparison of the Laryngeal Tube Suction and the Proseal laryngeal Mask Airway
      in anesthetized patients].
AB  - BACKGROUND: The Laryngeal Tube Suction (LTS : Smith Medical, Tokyo) is a new
      laryngeal tube that has an additional channel for gastric tube placement.
      Similarly, the Proseal Laryngeal Mask Airway (PLMA) also has a drain tube for
      gastric tube placement. This study compared the functions of these two devices.
      METHODS: Forty patients undergoing general anesthesia were randomly allocated to
      the group LTS (n = 20) or group PLMA (n = 20). Ease of insertion, quality of
      airway seal, ease of gastric tube insertion, fiberoptic view of the glottis
      through each device after placement, and postoperative sorethroat/hoarseness were
      investigated. RESULTS: There were no differences in patient characteristics and
      anesthetic background data for both groups. No differences concerning handling,
      quality of airway seal, ease of gastric tube insertion, and postoperative airway
      morbidity were detected between LTS and PLMA. In economical terms, LTS was more
      reasonable compared with PLMA. CONCLUSIONS: With respect to clinical function,
      the LTS and PLMA were similar and either device can be used to establish an
      effective airway in anesthetized patients.

PMID- 18807901
TI  - [Central pontine myelinolysis after living donor liver transplantation].
AB  - Central pontine myelinolysis (CPM) is the most serious central nervous system
      complication that could be seen after liver transplantation and represents an
      important source of mortality early after liver transplantation. CPM following
      liver transplantation was reported more and more in literatures, but the true
      incidence of CPM after living related liver transplantation (LDLT) remains
      unknown. However, with the introduction of magnetic resonance imaging (MRI),
      early recognition has become possible. In this report, we present a case of rapid
      resolution of CPM followed by MRI examinations.

PMID- 18807902
TI  - [Anesthetic management of an ALS patient with remifentanil].
AB  - An 82-year-old woman with amyotrophic lateral sclerosis (ALS) with bulbar
      paralysis, respiratory muscle paralysis, and arteriosclerosis obliterans (ASO) of
      the lower extremities, underwent uneventful general anesthesia with remifentanil
      and sevoflurane for bilateral below-knee amputation. Remifentanil is a potent
      ultra short-acting opioid analgesic drug, undergoes rapid metabolism by non
      specific tissue and plasma esterases, and does not accumulate to any clinically
      important degrees. Furthermore, when remifentanil is used together with propofol
      during anesthetic induction, successful tracheal intubation can be accomplished
      without muscle relaxants. These features of remifentanil make it an ideal agent
      for use in patients with neuromuscular diseases, including ALS, with higher risks
      of postoperative opioid-induced respiratory depression.

PMID- 18807903
TI  - [Perioperative and postoperative management of two patients with uncontrolled
      hyperthyroidism using short acting beta blocker, landiolol].
AB  - Thyroid storm, sudden onset of life-threatening manifestations of
      hyperthyroidism, often appears during and after surgery in patients with
      uncontrolled hyperthyroidism. We report perioperative and postoperative
      management of two such cases with uncontrolled hyperthyroidism. The first patient
      is a 41-year-old man with a past history of uncontrolled Graves disease, and was
      scheduled for emergency video-assisted thoracoscopic surgery for spontaneous
      pneumothorax. The second patient is a 25-year-old man with a past history of
      hypertension, and was scheduled for open reduction and internal fixation for
      mandibular fracture. In both patients, tachycardia and hypertension were observed
      at admission to the operating room. Therapy included the use of landiolol
      infusion, a short acting beta blocker, for control of tachycardia. Heart rate was
      controlled around 90 beats x min(-1) using landiolol during surgery. In each
      case, landiolol was administered until they can take long acting beta blocker and
      antithyroid drug orally. In the postoperative period, delirium appeared for a few
      hours in the first case, but no severe complications were observed in each case.
      Short acting beta blocker was useful for control of tachycardia in the
      perioperative and postoperative management of the patient with uncontrolled
      hyperthyroidism.

PMID- 18807904
TI  - [Severe arrhythmia after gastrectomy in patients with history of coronary bypass
      graft surgery using right gastroepiploic artery].
AB  - The authors reported two cases of severe arrhythmia after gastrectomy in the
      patients with history of coronary bypass grafting (CABG) using the right
      gastroepiploic artery. The first patient was a 64-year-old man who had undergone
      CABG involving bypassing between the right coronary artery and the right
      gastroepiploic artery 5 months before. Partial gastrectomy was performed without
      significant complications. However, he showed severe bradycardia and low output
      status with anuria in the intensive care unit (ICU). The second patient was a 74
      year-old man who had undergone CABG with the identical method 7 years before
      receiving partial gastrectomy. Although, surgery was performed with intraaortic
      balloon pumping for his mild heart failure, no other complication was observed
      during operation and ICU stay. Immediately after being moved to the ward on
      postoperative day 3, recurrent ventricular tachycardia occurred. Finally, the
      patient was implanted with an automatic defibrillator.

PMID- 18807905
TI  - [Two cases of anesthesia mumps in the upper parotid gland after general
      anesthesia in the lateral position].
AB  - We describe two cases of acute transient swelling of the upper side of parotid
      glands of the patients after general anesthesia in the lateral position. The
      serum amylase levels in the patients were not increased and the enlargement of
      the parotid gland was diagnosed as anesthesia mumps. Previous reports suggested
      that mechanical compression might produce the swelling of the secreting organ,
      but our patients showed temporal parotid enlargement in the upper free side.
      Although, pre-medication with atropine might become a cause of parotid gland
      swelling, we anesthetized these patients without anti-cholinergic drugs.
      Procedures of oro-tracheal intubation and stimuli of endotracheal tube may induce
      impairment of the normal flow of saliva and lead to enlargement of the parotid
      gland.

PMID- 18807906
TI  - [Case of primary pulmonary hypertension supported with non-invasive positive
      pressure ventilation].
AB  - We report a case of primary pulmonary hypertension supported with non-invasive
      positive pressure ventilation (NPPV). A 20-year-old woman was diagnosed as
      primary pulmonary hypertension at the age of 15 and we prepared for registration
      of cadaver lung transplantation at the age of 20. She suffered from hemoptysis
      and was transferred to our ICU. We performed NPPV with continuous positive airway
      pressure of 4-6 cmH2O. Her systolic pulmonary artery pressure estimated with
      echocardiography was reduced, lung congestion on chest X ray was improved, and
      arterial oxygenation was improved. Considering that her condition would
      deteriorate only with medical therapy, we planned living donor lung
      transplantation. However, she died from massive hemoptysis before lung
      transplantation.

PMID- 18807907
TI  - [Continuous intravenous administration of fentanyl reduces tenesmus after
      transurethral resection of the prostate (TUR-P)].
AB  - BACKGROUND: The relief from tenesmus is important after transurethral resection
      of the prostate (TUR-P). We evaluated the effect of continuous intravenous
      administration of fentanyl on the tenesmus. METHODS: Eleven patients receiving
      fentanyl infusion (fentanyl group) were compared with fourteen patients without
      fentanyl infusion (control group) retrospectively. All patients underwent TUR-P
      under spinal anesthesia with hyperbaric 0.5% bupivacaine 2.2-2.8 ml. In the
      fentanyl group, fentanyl infusion 25 microg x hr(-1) was started followed by
      fentanyl 50 microg administration postoperatively. RESULTS: In the fentanyl
      group, NSAIDs were needed in only one patient. Eleven patients in the control
      group, however, required NSAIDs and three of them needed additional pentazocine
      administration. The required amount of NSAIDs per patient was significantly
      smaller in the fentanyl group (Mann-Whitney U test, P < 0.01). In the fentanyl
      group, one patient had slight nausea but needed no care. Other side effects, such
      as respiratory depression, hypotension, bradycardia and somnolence were not
      observed. CONCLUSIONS: Continuous intravenous administration of fentanyl was very
      effective and safe enough for the tenesmus after TUR-EP.

PMID- 18807908
TI  - [Esophageal intubation: Can it be avoided with the airway scope (Pentax-AWS)?].
AB  - Airway scope (AWS) is a rigid indirect laryngoscope with integrated tube guidance
      and can improve laryngeal exposure compared to the conventional direct
      laryngoscope. It is expected that the clear and improved laryngeal view obtained
      with AWS can eliminate the risk of esophageal intubation. We, however,
      experienced 3 cases of esophageal intubation out of 600 clinical cases with AWS
      in 15 month after its market release. Two cases were by novice anesthesiologists
      with fewer than 10 intubation experiences with AWS. Although they had had more
      than 100 intubation experiences with Macintosh laryngoscope, they did not have
      sharp eye for incorrect intubation with AWS. The third case was performed by an
      experienced laryngoscopist but it was difficult to identify the glottic opening
      because patient had distracted airway anatomy due to laryngeal tumor. In all
      cases esophageal intubation was immediately noticed and airway was secured
      uneventfully. We conclude that intubation under vision with improved laryngeal
      view is still not sufficient to prevent esophageal intubation.

PMID- 18807909
TI  - [The application of statistical methods in chemical experiments].
AB  - Quality of the analyzed data has a major impact on reliability of the results.
      Application of statistical methods allows to reduce some stages of chemist's
      work, for example classification of the numerous data sets. The statistical
      methods are applied for preliminary evaluation of the data quality. In this case
      it is necessary to verify that the raw data base does not include large errors or
      outliers, which could influence the result of experiment. Data analysis, which is
      performed by chemometric techniques, rely on finding the most correlated
      attributes. Chemometry is used towards creation of the mathematical model of
      relation between analyzed property and numerous sets of described variables
      (parameters which affect measure). Modeling requires calculations towards model
      identification, checking its relevance, evaluation of the adequacy and
      determination of model's prognostic ability. The obtained model of relation could
      be used for the system optimization in the technological process, forecasting the
      values subsidiary conditioned upon known values described, also for control of
      the analytical system. The statistical methods are applied in chemical studies
      for data collection and analysis of chemical compounds for more efficient
      management of flow of the information. They allow to foreseen physical and
      biological properties of chemical compounds. The statistical methods are also
      applied for quality management in chemical analysis of contaminants including
      pesticide residues in foodstuff.

PMID- 18807910
TI  - [Benzo(a)pyrene contamination of vegetable oils].
AB  - Benzo(a)pyrene (B(a)P) analysis was carried out with glass chromatographic column
      with alumina followed by reverse phase high-performance liquid chromatography
      (HPLC) and spectrofluorometric detection. B(a)P level in 40 vegetable oils were
      as follow: from 0.11 to 0.38 microg/kg in olive; from 0.92 to 3.74 microg/kg in
      rape seed oils; from 0.11 to 2.25 microg/kg in sunflower oils and from 0.33 to
      1.26 microg/kg in soya oils. In another investigated oils: arachide (peanut)
      corn, safflower, linen, hempen, sesame, pumpkin seeds, grape seeds---values from
      0.10 to 1.44 microg/kg and 3.83 microg/kg in sea buckthorn oil were detected.
      B(a)P concentration in 4 from 40 investigated oils exceed the 2 ppb limit
      proposed by the European Commission. Heating of sample of oils: olive, rape,
      soya, linen, corn, sesame, peanut, in temp. 240 degrees C for 30 min. has not
      influence on decreased of B(a)P level.

PMID- 18807911
TI  - [Content and bioconcentration of mercury by European Blusher (Amanita rubescens)
      from Northern Poland].
AB  - Total mercury content have been determined in 45 fruiting bodies of European
      Blusher (Amanita rubescens) and soil substrate collected from three spatially
      distant sites at the Pomorskie Voivodeship in 2006-2007. Mercury analysis carried
      out was by cold-vapour atomic absorption (CV-AAS) with amalgamation on golden
      wool. The European Blusher effectively accumulated mercury and median BCF values
      of this element ranged from 9.5 to 24 for the caps and from 6.1 to 15 for the
      stipes. For the areas surveyed mean concentration values of total mercury ranged
      from 0.46 to 0.93 (0.098-3.2) microg/g dw for the caps, from 0.27 to 0.65 (0.077
      2.7) microg/g dw for the stipes and from 0.032 do 0.040 (0.0096-0.20) microg/g dw
      for soil substrate.

PMID- 18807912
TI  - [Mercury in three species of Suillus mushroom from some sites in Poland].
AB  - Total mercury content have been determined in fruiting bodies of Variegated
      Bolete (Suillus variegates), European Cow Bolete (S. bovinus) and Slippery Jack
      (S. luteus) and in underlying to mushroom's surface layer of soil substrate
      collected from several spatially distant one from another sites in Poland. All
      three Suillus mushroom species independent of the site characterized were by
      small mercury content. The arithmetic mean values of mercury concentration in
      caps and stipes, respectively, were: 0.17 +/- 0.07-0.22 +/- 0.12 and 0.047 +/-
      0.015-0.071 +/- 0.035 microg/g dry weight for Variegated Bolete; 0.28 +/- 0.11
      0.79 +/- 0.40 and 0.17 +/- 0.07- 0.51 +/- 0.22 microg/g dw for European Cow
      Bolete, and 0.095 +/- 0.082-0.17 +/- 0.05 and 0.045 +/- 0.026- 0.070 +/- 0.026
      microg/g dw for Slippery Jack. All three species of Suillus mushrooms bio
      concentrated mercury (BCF > 1). European Cow Bolete bioconcentrated mercury
      relatively more efficiently when compared to two other species, and means of BCF
      value of this element in its caps ranged from 18 +/- 10 to 45 +/- 20, and in
      stipes from 9.4 +/- 7.5 to 29 +/- 11. A level of surface soil pollution with
      mercury was low and averaged from 0.017 +/- 0.003 do 0.029 +/- 0.020 microg/g dw.

PMID- 18807913
TI  - [Content of selected metals in forest fruits depending on the harvest site].
AB  - Contents of selected metals (Pb, Cd, Cu, Zn, Fe, Mn) were determined in samples
      of forest fruits: blueberry, raspberry and wild strawberry harvested in Lublin
      region from areas considered as potentially not exposed to pollution
      (Skierbieszow Landscape Park) and potentially polluted areas (Cement Factory
      Rejowiec S.A.). Analyzed fruits originating from stands more exposed to pollution
      were characterized by higher lead (except from raspberry) as well as other metals
      contents than those from Krasiczyn commune. Among studied fruits, blueberry was
      distinguished by the lowest contents of Pb, Zn, Fe, Mn, wild strawberry contained
      the highest levels of Pb, Zn and Mn. Cadmium content in analyzed plant materials
      was high.

PMID- 18807914
TI  - [Study of the influence of raw material and processing conditions on acrylamide
      level in fried potato chips].
AB  - The aim of our study was to examine relation between the asparagine level in raw
      material and acrylamide concentration in chips made from different varieties of
      potato. Relation between colour of potato chips and acrylamide content was also
      examined. Acrylamide concentration in fried potato chips ranged from 376 to 2348
      microg/kg. We found the lowest acrylamide content in potato chips made from the
      Plant Breeding and Acclimatization Institute Irga and the highest in Irga bought
      in the Warsaw market. We didn't find significant correlation between the
      asparagine content in raw material and the acrylamide level in potato chips (r = 
      0.13). The colour intensity of fried chips positively correlated with acrylamide
      concentration independently from the potato varieties and sequence of frying (r =
      0.8045; p < 0.005).

PMID- 18807915
TI  - The determination of content of selenium in natural fruit juices by spectral
      methods.
AB  - The results of determination of trace quantites of selenium in various commercial
      natural fruit juices by three independent methods: atomic absorption spectrometry
      (AAS), spectrophotometry (UV-VIS) and spectrofluorometry (SF) were presented. The
      level of selenium in any of the analysed samples of fruit juices did not exceed
      the WHO recommended level of 0.010 mg/l for drinking water.

PMID- 18807916
TI  - [Estimation of selected bioelements content in vegetables].
AB  - Concentrations of Ca, P, Fe, Zn and Cu were determined in 30 different kinds of
      fresh vegetables available in sale. The contents of chemical elements (except
      phosphorus) were analysed, after dry mineralization, by flame atomic absorption
      spectrometry--AAS with deuterium background correction. The phosphorus was
      determined in the form of phosphormolybdate blue by spectrophotometric method.
      Reliability of the procedure was checked by the analysis of certified reference
      materials. The average contents (mg/100 g) of minerals in vegetables were as
      follows: 2.57 - 165 for Ca; 22.1 - 95.4 for P; 0.07 - 0.82 for Zn; 0.01 - 0.16
      for Cu and 0.27 - 3.31 for Fe. These measurements allowed to estimate the
      realisation of the recommended daily intake of bioelements with the analysed
      vegetables for an adult person.

PMID- 18807917
TI  - [Mineral elements content in smoked fish].
AB  - The content of macroelements (phosphorus, calcium, magnesium potassium and
      sodium) and microelements (copper, zinc, iron, manganese, chromium, selenium,
      fluorine and iodine) in the following smoked fish: sprat, mackerel, salmon,
      smoked herring and trout were determined. The most of calcium, phosphorus, iron,
      zinc, copper and manganese contain smoked sprat. The amount of calcium in fish's
      remaining species is considerably lower, and phosphorus approximated to his
      content in sprat. The selenium and the fluorine occur on approximate level in all
      examined fish, however the amount of iodine was diverse but high. Smoked salmon
      and trout contain the most iodine, and the least smoked herring, sprat and
      mackerel. Contribution of fish in the recommended daily intake for mineral
      elements was estimated.

PMID- 18807918
TI  - [Butterfish as a source of niacin].
AB  - The present study provides information about the concentrations of niacin in
      butterfish products. The concentrations of vitamin were determined by
      microbiological analytical methods. The results demonstrate that the analyzed
      fish were a good source ofniacin. Butterfish can provide the human organism with
      contents of niacin corresponding to 27 - 43% for female and 25 - 39% for male of
      RDA.

PMID- 18807919
TI  - [Folic acid and cobalamine intake in daily food rations of women from the region
      of Lower Silesia].
AB  - The aim of paper was to assess the folic acid and cobalamine women (n = 960). The
      information about vitamins intake were collected using 24-hour recall and diet
      history questionnaire. The intake of vitamins folic acid and cobalamine was too
      low. The mean folic acid content in the diets of 100 women from Lower Silesia was
      221.5 mcg and complied in 79% recommended level. The mean cobalamine content in
      the diets of 100 women from Lower Silesia was 2.9 mcg and complied in 97%
      recommended level. In examined group low knowledge about importance role of folic
      acid and cobalamine in health was noticed. Educational interventions are required
      to inform women and to increase its intake among them.

PMID- 18807920
TI  - [Evaluation of dietary fibre, soluble and insoluble fibre food intake in Polish
      households in years 1996-2005].
AB  - The aim of the study was food intake of dietary fibre and soluble and insoluble
      fibre intake in years 1996-2005 in six types of households. According to the
      households budget data, and literature mean values of dietary fiber and its
      fraction in food products food intakes of these compounds were calculated and
      compared to recommendations taking into consideration main sources of them. The
      obtained results indicated that the mean dietary fibre intake was 23.7 g/per
      person/day (19.9-28.5 g/per person/day). Dietary food intake depended on type of
      household, and was less dependent on year. The mean soluble fibre intake was 8.8
      g/per person/day (7.2-10.5 g/per person/day) and insoluble fibre was 14.9
      g/day/person (12.1-18.0 g/per person/day). In researched period we observed small
      increase soluble fibre intake, however decline insoluble fibre intake. The main
      food sources of dietary fibre were cereals, especially bakery, but in case of
      soluble fibre vegetables and fruit and their products.

PMID- 18807921
TI  - [Antioxidants content in selected conventionally and organically cultivated
      vegetables].
AB  - The purpose of the study was to check the antioxidants content in usually
      consumed vegetables in Poland as well as the interrelationship between them and
      the way of cultivation. The contents of vitamin C in cabbage and potatoes, beta
      carotene in carrot and phenolic compounds in onion were analysed. There were no
      statistically important differences in the content of analysed compounds between
      organically and conventionally cultivated vegetables. The only one was observed
      for vitamin C in conventional potatoes and for beta-carotene in cooked
      conventional carrot.

PMID- 18807922
TI  - [Intake of food products by obese inhibitans from Wroclaw].
AB  - The aim of the study was to asses food products intake in food ratio of women (n
      = 70) and men (n = 30) with BMI 27-40 from Wroclaw, which were patients of
      endocrynological section in Clinic Hospital in 2004. The 24 - hours recall and
      album of photographs of food products and dishes were used to estimate food
      products intake. Results of the study were compared with recommendation for
      adults in age 26-60 with low physical activity. In average food ratio the
      improperly high intake of meat and meat products (women 152% and men 198% of
      recommended level), fat (respectively 336% and 250%) and sugar and sweets (180%)
      were observed. The low intake of milk and milk products (women 71% and men 38% of
      recommendation) and vegetables and fruit (respectively 70% and 64%) were noticed.
      The way of nutrition of examined adults had many abnormalities predicted to
      increase body mass. The most errors including incorrect distribution of meals
      during the day, incorrect number of meals with snacks between them and too low
      physical activity was observed.

PMID- 18807923
TI  - [Dietary patterns and selected anthropometric parameters of nutritional status of
      men between 20 and 60 years old from Krakow population].
AB  - The purpose of research was to analyze relations between dietary patterns and
      anthropometric parameters of nutritional status among working men, living in big
      city population. Tests involved a group of 1451 men between 20 and 60 years old,
      employed in Steelworks of T. Sendzimir (HTS) in Krakow, Poland. Comparison was
      done for average values of anthropometric indexes of men in sections of 10 years
      of age and two categories of persons--of the least (I section) and of the most
      reasonable nutrition choices (II section). Research pointed out the relation
      between the quality measurement of nutrition method and some of anthropometric
      indexes of nutritional status. In selected sections of the least and of the most
      reasonable nutrition choices there were no differences between average values of
      4 skinfolds, waist and arm perimeter, Waist to Hip Ratio distribution index (WHR)
      and average values of Fat Free Mass (FFM). Unawares characteristically higher
      average values of BMI were found at men of 20-30 years old (23.91 vs. 25.45
      kg/m2, p < 0.05) and 50-60 years old (26.42 vs. 28.00 kg/m2, p = 0.01) declaring
      more rational nutrition behaviors. Similar regularity was ascertained for
      percentage of body fat tissue (%BF); higher nutrition habit mark is accompanied
      with higher average value of %BF at 20-30 years old (15.17 vs. 18.24%, p < 0.01)
      and 50-60 years old (22.76 vs. 25.01, p < 0.05).

PMID- 18807924
TI  - [Mitochondria in cell life, death and disease].
AB  - In animal cell, mitochondria are the main sites of the synthesis of ATP required
      for cell functioning and survival. On the other hand, mitochondria play a key
      role in initiating cell programmed death (apoptosis). In addition, defects in the
      mitochondrial genome and in the nuclear genome encoding mitochondrial proteins
      may result in malfunctioning of these organelles and, as result, in diseases of
      the whole organism. This article contains basic information on the functioning of
      oxidative phosphorylation and on mitochondrial production of reactive oxygen
      species. It also describes initiation of apoptosis at the mitochondrial level.
      Finally, it briefly presents some most common genetic defects responsible for
      "mitochondrial diseases".

PMID- 18807925
TI  - [Evolution of the mitochondrial DNA and its expression system--comparison between
      animal and plant kingdom].
AB  - The information about features of the Eukaryotic cells is maintained not only in
      the nucleus, but also in the extranuclear genomes localized in mitochondria and
      chloroplasts. Comparison between plant and animal mitochondrial genomes allows to
      perceive two extremely distinct evolution strategies. Animals clearly tend to
      reduce the size of the mitochondrial genome to the minimum. In accordance with
      this, the simplification in decoding of genetic information present in the genome
      is observed. On the contrary, plant mitochondrial genomes tend to increase their
      size. Accumulation of extraordinary solutions for maintaining and expression of
      genetic information present in the genome is the second distinctive feature of
      plant mitochondria.

PMID- 18807926
TI  - [The impact of mtDNA mutations on proteins structure in selected types of
      cancer].
AB  - Recently published papers report a large number of mitochondrial DNA mutations in
      many different cancer types, but their significance for electron transport chain
      proteins remains unknown. This review covers structural mutations of
      mitochondrial genes, choosing prostate cancer, esophageal cancer and epithelioma
      as research models. As all mitochondrial genes encode subunits of the electron
      transport chain, the review focuses on the consequences of structural mutations
      on cell metabolism.

PMID- 18807927
TI  - [Mitochondrial diseases in children including Leigh syndrome--biochemical and
      molecular background].
AB  - Mitochondrial diseases in children are more frequently caused by mutations in
      nuclear DNA then in mtDNA. Special clinical phenotypes are associated with the
      mutations in SURF1 gene, in SCO2 gene and with mtDNA depletion syndromes. Leigh
      syndrome is the most common clinical presentation of various mitochondrial
      disorders during childhood. Elevation of lactate in blood, cerebrospinal fluid
      and urine is a simple biochemical marker of mitochondrial disorders but its
      specificity and sensitivity are low. Biochemical investigation of muscle biopsy
      and search for mitochondrial mutations remain a gold standard in the diagnosis.
      The standarized diagnostic criteria to establish level of diagnostic certainty
      (possible, probable, definite) are proposed to be used in practice; these include
      clinical features, neuroimaging and muscle biopsy investigations. Further
      research directions to improve our understanding of mitochondrial pathologies in
      children are suggested.

PMID- 18807928
TI  - [Mitochondrial neuroprotection].
AB  - Mitochondria play a key function in cellular metabolism. Additionally to ATP
      synthesis, mitochondria may buffor cytosolic calcium ions and generate reactive
      oxygen species. Due to these processes, mitochondria are involved in complex
      cytoprotective phenomena. Neuroprotection is very often based on changes in the
      integrity of mitochondrial membranes. In this report potential neuroprotective
      role of mitochondrial ion channels is discussed.

PMID- 18807929
TI  - [Mitochondrial uncoupling proteins: regulation and physiological role].
AB  - Uncoupling proteins (UCPs), members of mitochondrial carrier family, are present
      in mitochondrial inner membrane and mediate free fatty acid-activated, purine
      nucleotide-inhibited H+ re-uptake. UCPs can modulate the tightness of coupling
      between mitochondrial respiration and ATP synthesis. A physiological function of
      the first described UCP, UCP1 or termogenin, present in mitochondria of mammalian
      brown adipose tissues is well established. UCP1 plays a role in nonshivering
      thermogenesis in mammals. The widespread presence of UCPs in eukaryotes, in non
      thermogenic tissues of animals, plants and in unicellular organisms implies that
      these proteins may elicit other functions than thermogenesis. However, the
      physiological functions of UCP1 homologues are still under debate. They can
      regulate energy metabolism through modulation of the electrochemical proton
      gradient and production of ROS. Functional activation of UCPs is proposed to
      decrease ROS production. Moreover, products of lipid peroxidation can activate
      UCPs and promote feedback down-regulation of mitochondrial ROS production.

PMID- 18807930
TI  - [Uncoupling proteins in modulation of mitochondrial functions--therapeutic
      prospects].
AB  - Enormous interest in mitochondrial uncoupling proteins (UCPs) is caused by
      relevant impact of these energy-dissipating systems on cellular energy
      transduction. A key role of UCPs in regulation of mitochondrial metabolism is
      supported by existence of their different isoforms in various mammalian tissues.
      Recent studies have shown that UCPs have an important part in pathogenesis of
      various disorders, such as obesity, type-2 diabetes, cachexia, aging or tumor.
      The obscure roles of UCPs in normal physiology and their emerging role in
      pathophysiology, provide exciting potential for further investigation. However,
      neither the exact physiological nor biochemical roles of UCP homologues are well
      understood. Therefore, providing mechanistic explanation of their functions in
      cellular physiology may be the basis for potential farmacological targeting of
      UCPs in future on clinical scale.

PMID- 18807931
TI  - [Endothelial mitochondria--a novel target for pharmacology of endothelial
      dysfunction].
AB  - Vascular endothelium the inside layer of the cardiovascular system is presently
      looked upon as an important paracrine, autocrine and endocrine organ that
      determines the health of the cardiovascular system. In fact, healthy endothelium
      is essential for homeostasis of cardiovascular system, while endothelial
      dyfunction leads to cardiovascular diseases including atherosclerosis, diabetes
      and heart failure. Endothelial dysfunction is tightly linked to the
      overproduction of reactive oxygen species, development of oxidant stress and
      inflammatory response of endothelium. Mitochondria of the vascular endothelium
      seem to be an important player in these processes. In contrast to numerous cell
      types, synthesis of ATP in endothelium occurs in major part via a glycolytic
      pathway and endothelium seem to be relatively independent of the mitochondrial
      pathway of energy supply. However, as evident from recent studies, mitochondrial
      pathways of free radicals production tighly linked to mitochondrial and cytosol
      changes in the ion homeostasis play an important role in the regulation of
      endothelial inflammatory response, in the development of oxidative stress and
      apoptosis of vascular endothelium. Therefore, endothelial mitochondria appears
      critical in the regulation of endothelial functions and represent a novel target
      in pharmacology of endothelial dysfunction in cardiovascular diseases.

PMID- 18807932
TI  - [Protein kinases in mitochondria].
AB  - Mitochondria, besides playing a central role in energy metabolism within the
      cell, are involved in a cohort of other processes like cellular differentiation
      and apoptosis. Investigations during recent few years have shown that protein
      kinases, including PKA, PKB/Akt, PKC, Raf-1, p38 MAPK, JNK, ERK1/2, Src, Fyn and
      Csk, may directly interact with mitochondrial proteins. Their role mainly
      concentrates at phosphorylation of pro- and anti-apoptotic proteins (Bad, Bax,
      Bcl-2, Bcl-xL), phosphorylation/modification of electron transport chain proteins
      (complex I, COIV), MPTP forming proteins VDAC and ANT, proteins of mitochondrial
      ATP-sensitive potassium channel (mitoK(ATP)) and phospholipid scramblase 3
      (PLSCR3). Many experimental data showed the presence of protein kinases in the
      outer and inner mitochondrial membranes as well as in the mitochondrial matrix
      during in vitro cell stimulations, in neurodegenerative diseases and in in vivo
      ischaemia heart preconditioning. These data show that translocation of protein
      kinases to mitochondria plays an important role especially during
      ischaemia/reperfusion in brain and heart.

PMID- 18807933
TI  - [Application of "blue native" electrophoresis in the studies of mitochondrial
      respiratory chain complexes in physiology and pathology].
AB  - "Blue Native" polyacrylamide gel electrophoresis (BN-PAGE), originally described
      by Schagger and von Jagow in 1991, is an elegant method to study protein
      complexes from mitochondrial membranes. BN-PAGE, commonly used in molecular
      biology to study composition of protein complexes and protein-protein
      interactions, enables separation of respiratory chain complexes keeping their
      properties and enzymatic activities unchanged. BN-PAGE, supplemented by other
      methods, e.g. in gel activity assay, SDS-PAGE (as a first or second dimension)
      can be successfully adapted for diagnosis of mitochondrial diseases connected
      with abnormalities of the respiratory chain. Therefore, to make a correct
      diagnosis of the deficiency of respiratory chain complexes, other methods, as
      histochemical colorimetric reactions allowing evaluation of the OXPHOS catalytic
      activity in individual cells and spectrophotometric technique should be used
      simultaneously with BN-PAGE.

PMID- 18807934
TI  - [Neural mechanisms of intelligence, emotion, and intention].
AB  - The limbic system (comprising the amygdala and the anterior cingulate cortex) and
      the prefrontal cortex (the orbital and dorsolateral prefrontal cortices) have
      been implicated in emotional and behavioral control. Selective lesion studies in
      rodents suggest that the basolateral nucleus of the amygdala, which is a critical
      subnucleus within the amygdala, plays a critical role in appetitive instrumental
      behaviors. On the other hand, the central nucleus of the amygdala directly
      receives afferents from the lateral nucleus of the amygdala. These 2 nuclei
      (central and lateral) of the amygdala are implicated in the learning of reflexive
      behavior (e.g., orienting, startle, and approaching behaviors) and autonomic
      responses (e.g., heart rate and blood pressure) during pavlovian conditioning.
      The caudal part of the anterior cingulate cortex (cognitive subdivision) is
      involved in monitoring and evaluating of the outcome of an indivisual's actions.
      However, the orbital cortex and the rostral part of the anterior cingulate cortex
      (affective subdivision) is involved in the biological evaluation of external
      sensory stimuli and events induced by stimuli originating from sources other than
      the individual. Based on these functions, the cognitive subdivision of the
      anterior cingulate cortex contributes to guiding and selecting actions that yield
      the optimal outcome, while the affective subdivision focuses on external aversive
      or rewarding stimuli, and guides appetitive or avoidance behaviors toward or away
      from these external stimuli. The dorsolateral prefrontal cortex is involved in
      predicting of the outcome of own action, and the evaluation of the outcome for
      guiding optimal behaviors is based on its close reciprocal connections with the
      limbic system. These 4 regions of the brain interact with each other and work
      complementarily. In the present review, the abovementioned functions of the
      limbic system and prefrontal cortex in primates are discussed with regard to the
      findings of previous neurophysiological studies in which neuronal responses in
      these brain regions were analyzed in monkeys and rats.

PMID- 18807935
TI  - [Development of intellect, emotion, and intentions, and their neuronal systems].
AB  - Intellect, emotion and intentions, the major components of the human mentality,
      are neurologically correlated to memory and sensorimotor integration, the
      neuronal system consisting of the amygdale and hypothalamus, and motivation and
      learning, respectively. Development of these neuronal processes was evaluated by
      correlating the pathophysiologies of idiopathic developmental neuropsychiatric
      disorders and developmental courses of sleep parameters, sleep-wake rhythm (SWR),
      and locomotion. The memory system and sensory pathways develop by the 9th
      gestational months. Habituation or dorsal bundle extinction (DBE) develop after
      the 34th gestational week. In the first 4 months after birth, DBE is consolidated
      and fine tuning of the primary sensory cortex and its neuronal connection to the
      unimodal sensory association area along with functional lateralization of the
      cortex are accomplished. After 4 months, restriction of atonia in the REM stage
      enables the integrative function of the brain and induces synaptogenesis of the
      cortex around 6 months and locomotion in late infancy by activating the
      dopaminergic (DA) neurons induces synaptogenesis of the frontal cortex.
      Locomotion in early infancy involves functional specialization of the cortex and
      in childhood with development of biphasic SWR activation of the areas of the
      prefrontal cortex. Development of emotions reflects in the development of
      personal communication and the arousal function of the hypothalamus. The former
      is shown in the mother-child relationship in the first 4 months, in communication
      with adults and playmates in late infancy to early childhood, and in development
      of social relationships with sympathy by the early school age with functional
      maturation of the orbitofrontal cortex. The latter is demonstrated in the
      secretion of melatonin during night time by 4 months, in the circadian rhythm of
      body temperature by 8 months, and in the secretion of the growth hormone by 4-5
      years with synchronization to the SWR modulated by the brainstem aminergic
      neurons. For this purpose, nursing according to the day-night light-dark cycle is
      essential right from early infancy. The deep cerebellar nuclei involved in
      learning develop by the 9th gestational month. The DA neurons activated in late
      infancy modulate the nuclei of the basal ganglia and the association cortex for
      learning. Motivation starts with activation of the PPN in infancy by crawling
      which makes DA neurons as the lead. In late childhood, DA neurons along with 5HT
      neurons activate the anterior cingulate area and establish the neuronal process
      for learning with motivation.

PMID- 18807936
TI  - [Neural mechanisms of decision making].
AB  - Decision-making plays an important role in the transformation of incoming sensory
      information to purposeful actions. Many decisions have important biological and
      social consequences, while others may have a more limited impact on our everyday
      life. The neural mechanisms of decision-making currently constitute an important
      subject under intense investigation in the field of cognitive and behavioral
      neuroscience. Among the investigations, on this topic, those involving sensory
      discrimination tasks using visual motion have provided a wealth of information
      about the nature of the neural circuitry required to perform perceptual decision
      making. For example, by using a motion discrimination task, Shadlen and Newsome
      have shown an essential role of area LIP in perceptual decision-making. On the
      other hand, the importance of reward and reward expectations as determinants of
      decision-making is increasingly appreciated. In particular, reinforcement
      learning and economic theories, such as game theory, have provided valuable
      insights into the brain functions related to decision-making. By using a
      competitive game analogous to matching pennies against a computer, Lee's group
      showed that in monkeys, previous selections modulated prefrontal neural activity
      and that this modulation affected the current choice behavior. The prefrontal
      cortex has been shown to participate in decision-making in free-choice
      conditions. By using a task involving the free choice of 1 target from multiple
      saccade targets, Funahashi's group examined the prefrontal participation in
      decision-making in a free-choice condition. They compared the activities of
      prefrontal neurons during an oculomotor delay task with forced-choice conditions
      and free-choice conditions and identified the neural components reflecting the
      underlying decision-making processes. Although several attempts have been made to
      understand the neural mechanisms of decision-making, further investigations are
      required to fully understand these mechanisms. Future studies should evaluate the
      effects of emotions on decision-making and attempt to integrate the
      neurophysiological, psychological, and computational approaches to decision
      making.

PMID- 18807937
TI  - [A brain-like computer involving emotion and volition].
AB  - This paper outlines the concept of "Associative Interacting Intelligence" with
      regard to a brain-like computer that evolves by learning the relationship between
      sensory input and behavioral output through active interaction with the real
      world environment. We developed the architecture of this intelligent system by
      using hypotheses based on the established features of brain function. Our central
      hypotheses are as follows: (1) intellect, emotion, and volition are processed by
      interactions between parts of the new brain, the old brain, and the body, (2) the
      heterogeneous hardware architecture of the brain is ontogenically developed, (3)
      the anatomically modular hardware structure of the brain, (4) reinforcement
      learning in the brain is motivation-based, and (5) the firing properties of
      neurons vary. The 2 different levels of our model, which challenges our concepts
      of the old brain, were proposed using these hypotheses. The spiking neuron model
      of the basal ganglia circuitry demonstrated the capability of our model to
      perform probabilistic selections of behavior. In addition, the model also
      indicated that the selection probability and execution time could be modulated.
      The parallel modular neural network model for reinforcement learning illustrated
      the effectiveness of rich internal state representation and internal rewards for
      achieving a goal in a reduced number of trials. The results of the models showed
      their potential toward the "Associative Interacting Intelligence", especially
      regarding efficiency, flexibility, and adaptability. However, many issues, have
      yet to be addressed and resolved. Our models, which are yet to be tested in
      detail, must be morphed to a human body in order to demonstrate the ability of
      these models to reproduce learned abilities. The future success of our study will
      depend on multidisciplinary collaborations and advances in allied research areas.

PMID- 18807938
TI  - [Pathological gambling and Parkinson disease].
AB  - Pathological gambling (PG) is defined by the DSM IV criteria as inappropriate,
      persistent, and maladaptive gambling behavior that has repercussions on family,
      personal, and professional life. It is classified as an impulse control disorder
      and is widely understood as a nonpharmacological addiction. PG has been reported
      as a complication in the treatment of Parkinson disease (PD). The prevalence of
      PG in PD has been reported to range between 1.7 and 7% compared to a prevalence
      of approximately 1% in the general population. Though there is no survey that
      indicates the prevalence of PG in Japanese PD patients, problematic gambling
      behaviors in PD are occasionally observed. In addition to PG other impulse
      control behaviors and punding (repetitive stereotyped behavior) are recognized as
      components of the dopamine dysregulation syndrome (DDS), which is characterized
      by the compulsive use of dopaminergic medications, including levodopa and
      subcutaneous apomorphine. Though PG can occur with DDS it often occurs in
      isolation. The vast majority of PG seen in PD is related to dopamine agonists
      (DA). With regard to the administration of oral DA, pramipexole may induce a
      higher degree of PG than other types of oral DA due to its disproportionate
      stimulation of dopamine D3 receptors. However, the differences between the
      observed effects of various classes of oral DA were insignificant. PG associated
      with levodopa mono-therapy is uncommon, but in the majority of cases levodopa is
      co-prescribed. Subthalamic nucleus deep brain stimulation (STN-DBS) was recently
      introduced to treat advanced PD. An improvement in PG symptoms following STN-DBS
      has been reported due to a marked decrease in dopaminergic medications. However,
      in some patients, PG developed following STN-DBS despite the significant
      reduction or discontinuation of DA. STN-DBS per se may be a potential initiator
      of PG. Younger age of PD onset, novelty seeking personality traits, history of
      alcohol abuse, and impulsivity traits were significant predictors of PG. Patients
      especially those with individual susceptibility to PG should be warned of the
      potential risks of PG before DA treatment is initiated.

PMID- 18807939
TI  - [Anti-nMDA receptor encephalitis--clinical manifestations and pathophysiology].
AB  - Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a new category of
      treatment-responsive encephalitis associated with "anti-NMDAR antibodies", which
      are antibodies to the NR1/NR2 heteromers of NMDAR. The antibodies are detected in
      the CSF/serum of young women with ovarian teratoma, who typically develop
      schizophrenia-like psychiatric symptoms, usually preceded by fever, headache, or
      viral infection-like illness. After reaching the peak of psychosis, most patients
      developed seizures followed by an unresponsive/catatonic state, decreased level
      of consciousness, central hypoventilation frequently requiring mechanical
      ventilation, orofacial-limb dyskinesias, and autonomic symptoms. Brain MRI is
      usually unremarkable but focal enhancement or medial temporal lobe abnormalities
      can be observed. The CSF reveals nonspecific changes. EEG often reveals diffuse
      delta slowing without paroxysmal discharges, despite frequent bouts of seizures.
      This is a highly characteristic syndrome evolving in 5 stages, namely, the
      prodromal phase, psychotic phase, unresponsive phase, hyperkinetic phase, and
      gradual recovery phase. The hyperkinetic phase is the most prolonged and crucial.
      This disorder is usually severe and can be fatal, but it is potentially
      reversible. Once patients overcome the hyperkinetic phase, gradual improvement is
      expected with in months and full recovery can also be expected over 3 or more
      years. Ovarian teratoma-associated limbic encephalitis (OTLE) was first reported
      in 1997 when this syndrome was reported independently in 1 Japanese girl and 1
      woman, both of whom improved following tumor resection. In 2005, Dalmau and his
      research group first demonstrated antibodies to novel neuronal cell membrane
      antigens in 4 women with OTLE in a non-permeabilized culture of hippocampal
      neurons. Two years later, they identified conformal extracellular epitopes
      present in the NR1/NR2B heteromers of NMDAR, which are expressed in the
      hippocampus/forebrain. The target extracellular epitopes are not detectable by
      immunoblotting, and should not be confused with the linear epitopes of NR2B
      subunits (also known as epsilon2). The antibodies disappear with clinical
      improvement, suggesting their pathogenic role. Autopsies revealed IgG deposits in
      the hippocampus, extensive microgliosis, rare T-cell infiltrates, and neuronal
      degeneration predominantly involving, but not restricted to, the hippocampus. The
      nervous tissues of the tumors exhibit not only strong expression of the NR2B
      subunits but also reactivity with the patients' antibodies. The pathogenesis
      remains unknown; however, this disorder is considered to be an antibody-mediated
      encephalitis. Based on the current NMDAR hypofunction hypothesis of
      schizophrenia, we speculate that the antibodies may cause inhibition rather than
      stimulation of NMDARs in presynaptic GABAergic interneurons, causing a reduction
      in GABA release. This results in disinhibition of postsynaptic glutamatergic
      transmission, excessive release of glutamate in the prefrontal/subcortical
      structures, and glutamate and dopamine dysregulation that might contribute to
      development of schizophrenia-like psychosis and bizarre dyskinesias. The
      antibodies were initially found only in young women with teratoma in the ovaries.
      However, recent studies show that this disorder can occur even in the absence of
      teratoma in up to 35% of patients, and even boys and adult men had been affected.
      Although recovery occurs without the need for tumor removal, the severity and
      extended duration of symptoms support tumor removal. Combined therapy including
      tumor resection and immunotherapy is recommended. In this review, we also discuss
      the relationship between anti-NMDAR encephalitis and related disorders, including
      acute diffuse lymphocytic meningoencephalitis and acute juvenile female non
      herpetic encephalitis (AJFNHE).

PMID- 18807940
TI  - [Pontine hemorrhage in a patient with type 1 renal tubular acidosis associated
      with osmotic demyelination syndrome].
AB  - Here, we report the case of a 23-year-old man with type 1 renal tubular acidosis
      (RTA) associated with osmotic demyelination syndrome (ODS) who developed pontine
      hemorrhage. Acute progressive tetraparesis had developed during the clinical
      course of the RTA. Neurological examination revealed bilateral weakness in all 4
      limbs associated with severe hypokalemia (K 1.4 mEq/L). He experienced a sudden
      onset of general convulsions and mutism during the treatment for metabolic
      acidosis and hypokalemia. The T2-weighted MR image of the brain revealed multiple
      hyperintense signal lesions in the central pons as well as in the extrapontine
      sites of the bilateral cortical and subcortical areas in the frontal and parietal
      lobes. A T2-star (T2*)-weighted MR image showed focal hemorrhagic lesions in the
      lower pons. On the basis of the diagnosis of ODS, he underwent corticosteroid and
      thyrotropin-releasing hormone therapy, after which his neurological signs and
      symptoms have gradually reduced. While analyzing the possible etiology, it has
      been suggested that osmotic vascular injuries induced by elevated levels of serum
      potassium and osmolarity give rise to edema and vascular endothelial damage;
      these conditions, consequently lead to hemorrhagic necrosis. Physicians need to
      be aware that RTA patients may develop ODS after hypokalemia, and the potassium
      levels need to be corrected carefully. (Received: November 6, 2007, Accepted:
      June 11, 2008)

PMID- 18807941
TI  - [Successful removal of clots from embolic carotid occlusion by aspiration with a
      syringe--case report].
AB  - An 84-year-old woman who had experienced a sudden onset of stupor and total
      aphasia and right-side hemiparesis was admitted to our institution. Emergency MR
      (diffusion-weighted images: DWIs) studies revealed ischemic changes in the
      territory of the left middle cerebral artery; findings from the perfusion
      weighted images (PWIs) has suggested a reduction of the cerebral blood flow. In
      addition, the MR angiograms showed no signals in the left carotid-middle cerebral
      artery. An emergency removal of the clot the carotid artery was attempted after
      an adaptive determination of revascularization was performed using MRI
      (DWIs/PWIs) during the acute stage. An emergency cerebral angiography
      demonstrated occlusion of the left internal carotid artery (ICA). In order to
      prevent the migration of thrombus into the peripheral arteries, the proximal
      blood flow was blocked using a 9-F guiding catheter with a coaxial balloon.
      Manual aspiration through the catheter with a 10-ml syringe resulted in effective
      removal of the thrombus. The thrombus was thus removed successfully, and the
      cerebral angiography after clot removal therapy (CRT) demonstrated complete
      recanalization of the left ICA. The patient's National Institutes of Health
      Stroke score decreased from 25 to 1 at 8 days after clot removal and a good 3
      month clinical outcome was achieved. CRT by simple aspiration may be considered
      as a feasible and effective treatment modality for patients with embolic carotid
      occlusion. Received: December 18, 2007, Accepted: June 4, 2008

PMID- 18807942
TI  - [Excimer laser angioplasty for subclavian artery stenosis--case report].
AB  - Endovascular angioplasty for subclavian artery stenosis is effective and less
      invasive than other methods; however, it is difficult to advance guidewires or
      balloon catheters through severely stenotic lesions. We report a case of
      subclavian artery stenosis treated with excimer laser angioplasty. A 58-year-old
      man with hypertension and hyperlipidemia was admitted to a hospital with
      different blood pressure in each arm. A CT scan revealed left subclavian artery
      stenosis, and the patient was transferred to our hospital. An angiogram revealed
      a severely stenotic lesion in his left subclavian artery, representing subclavian
      steal phenomenon. Endovascular angioplasty was performed under local anesthesia
      with embolic protection for the left vertebral artery. The guidewire successfully
      crossed the lesion, and stepwise balloon angioplasty was performed using
      increasing balloon sizes from 1.5 to 2.0 mm; however, the next size balloon
      catheter could not cross the lesion, and we therefore decided to use an excimer
      laser catheter. After laser ablation, revascularization was performed via stent
      placement. The patient's symptoms and subclavian steal phenomenon improved, and
      the post-operative course was uneventful. Excimer laser angioplasty appears to be
      effective in the treatment of occlusive lesions that cannot be crossed using a
      balloon catheter.

PMID- 18807943
TI  - [Transient lesion in the splenium of the corpus callosum caused by diffuse axonal
      injury].

PMID- 18807944
TI  - [Reversible posterior leukoencephalopathy syndrome with the neuroradiological
      abnormalities predominantly in the brainstem].

PMID- 18807945
TI  - [Case of multiple brain infarction with MPO-ANCA].

PMID- 18807946
TI  - [SEM studies on the connective tissue cores of the lingual papillae of the
      northern goshawk (Accipiter gentilis)].
AB  - The lingual papillae and their connective tissue cores (CTCs) of the northern
      goshawk were examined by scanning electron microscopy (SEM). The length of the
      tongue was approximately 2.5 cm. The median groove divided the body of the tongue
      into symmetrical parts. At a point approximately 2/3 of the length, there were
      large conical papillae between the body and the root of the tongue, the apices of
      which were pointed towards the posterior part of the tongue. Under the light
      microscopy, the filiform papillae of the dorsal surface in the lingual body
      showed the desquamate cells of non-keratinized epithelium. There were openings of
      the lingual glands on the anterior part and root of the tongue. The lingual
      papillae and their CTCs of the northern goshawk had a structure similar to those
      of the white tailed eagle and black kite.

PMID- 18807947
TI  - [The physical therapy undergraduate students' responses to the gross human
      anatomy subjects].
AB  - Instruction in gross human anatomy is one of the important items in the subject
      for co-medical students of the physical therapist course. The physical therapy
      undergraduate students are required to have a solid understanding of the
      structure and formation of the human body. Therefore, their good-understanding of
      the course on the gross human anatomy and their experience of the gross human
      anatomy laboratory (observation practice) are acquired to improve their knowledge
      of the human body. To clarify the student responses to the gross human anatomy
      course including the gross human anatomy laboratory, several questionnaires were
      administered to the freshman physical therapy undergraduate student for two
      years. We found that more than 80% of the students, who felt a negative attitude
      for gross human anatomy before the course started, had a positive attitude about
      the gross human anatomy after going through the course. The experience of the
      gross human anatomy laboratory increased the students' activity of learning and
      they thought more about the dignity of being human after the course than before
      viewing. In addition, the results suggested that the multiple experiences of the
      gross human anatomy course are useful for the physical therapy undergraduate
      students to improve the quality of their understanding of the human body.

PMID- 18807948
TI  - [Attempt to reduce the formaldehyde concentration by blowing cooled fresh air
      down in to the breathing zone of medical students from an admission port on the
      ceiling during gross anatomy class].
AB  - Cadavers in gross anatomy laboratories at most medical schools are conventionally
      embalmed in formaldehyde solution, which is carcinogenic to humans. Medical
      students and instructors are thus exposed to formaldehyde vapors emitted from
      cadavers during dissection. To reduce high formaldehyde concentrations in the
      breathing zone above cadavers being examined by anatomy medical students
      provisionally, dissection beds were located under existing admission ports on the
      ceiling to supply cooled fresh air from the admission port blowing downward on to
      the cadaver. In all cases, compared to normal condition, the downward flow of
      cooled fresh air from an admission port reduced formaldehyde concentrations by
      0.09-0.98 ppm and reduced to 12.6-65.4% in the air above a cadaver in the
      breathing zone of students. The formaldehyde concentrations above cadavers under
      admission ports were not more than the formaldehyde concentrations between beds
      representing the indoor formaldehyde concentrations. Although the application of
      an existing admission port on the ceiling in this study did not remove
      formaldehyde, the downflow of cooled fresh air using this system reduced the
      formaldehyde concentration in the air above cadavers being attended by anatomy
      students during dissections. These results suggest the need for reducing
      formaldehyde levels in gross anatomy laboratories using fundamental
      countermeasures in order to satisfy the guidelines of 0.08 ppm established by the
      World Health Organization and the Japan Ministry of Health, Labor and Welfare.

PMID- 18807949
TI  - Can digital technology solve every dental challenge?

PMID- 18807950
TI  - How to change our curriculum to improve access to care.

PMID- 18807952
TI  - HIV-1 replication without integration.

PMID- 18807951
TI  - A clinical case with Adper Scotchbond SE self-etch adhesive.

PMID- 18807953
TI  - A simplified aesthetic concept: historical review and current clinical
      application.

PMID- 18807954
TI  - The use of mineral trioxide aggregate to repair iatrogenic perforations.

PMID- 18807955
TI  - The future of endodontics, Part 1. Observations by an endodontist-implant
      surgeon.

PMID- 18807956
TI  - Moving your practice into the digital age.

PMID- 18807957
TI  - Buyers' guide to practice management software. Trusting your colleagues.

PMID- 18807958
TI  - Functional-cosmetic dentistry: a full-mouth smile makeover. Part 1.

PMID- 18807959
TI  - The evolution of digital dentistry and the digital dental team.

PMID- 18807960
TI  - A new helping-hand concept for Invisalign users.

PMID- 18807961
TI  - Quadrant rehabilitation with implants and CAD/CAM crowns.

PMID- 18807962
TI  - Pediatric CAD/CAM applications for the general practitioner. Part 1.

PMID- 18807963
TI  - Future challenges for the doctor-technician team.

PMID- 18807964
TI  - Online medical and dental history submission for patients.

PMID- 18807965
TI  - Developing a comprehensive life plan, Part 2: 365 days of freedom.

PMID- 18807966
TI  - Operator stools: How selection and adjustment impact your health.

PMID- 18807967
TI  - Buyers' guide to chairs. Dental chairs: high tech and high comfort.

PMID- 18807968
TI  - [Technical innovation and development of industrial biotechnology--special
      preface of China Summit Forum on Industrial Biotechnology Development/2008].

PMID- 18807969
TI  - [Solid wastes treatment process and biohydrogen].
AB  - As a clean energy source and industrial material, hydrogen is very valuable.
      Electrolysis of water and chemical methods are well-known for producing hydrogen,
      however, all of these methods need additional energy supply. Besides highly
      energy cost, the chemical methods will lead to serious environment pollution.
      Compared with traditional methods, biological production of hydrogen has showed
      significant advantages. Bio-hydrogen can be produced by anaerobic and
      photosynthetic microorganisms during treatment of organic waste. It provides a
      low cost method for producing hydrogen gas, and a way of utilizing waste at the
      same time. This paper summarized the procedures of treatment of solid waste and
      the production of bio-hydrogen.

PMID- 18807970
TI  - [Microbial biosynthesis and biotransformation of indigo and indigo-like
      pigments].
AB  - Indigo and indigo-like pigments are widely used in the industry of textile, food
      and medicine. Now people pays more and more attention to developing an
      alternative method of indigo production which is "environment-friendy",
      especially microbial biosynthesis of indigo. Many microorganisms involved in the
      biosynthesis of indigo have been isolated and characterized, and monooxygenase
      and dioxygenase have been identified to catalyze indigo biosynthesis. Some genes
      encoding for these enzymes have been cloned and used to construct "engineering
      bacteria". With this kind of bacteria, more efficient fermentation systems for
      indigo production have been exploited. In the meantime, biotransformation of the
      indigo produced by microorganisms has been under investigation. These progresses
      will bring us a greener method of indigo and indigo-like pigments production.

PMID- 18807971
TI  - [Biosynthesis, fermentation and application of vitamin B12--a review].
AB  - Vitamin B12 is an important nutrient widely used in feed, food and medicine
      field. China is the primary producing area and the VB12 production is 27 t in
      2007, 77% of total production in the world. VB12 is the most complex small
      molecule difficult to chemosynthesize. It ismanufactured by bacteria and archaea
      via two alternative routes, aerobic or anaerobic pathway. The main strains used
      in industry fermentation are Propionibacterium freudenrechii and Pseudomonas
      denitrificans. The basic characteristics, biosynthesis and fermentation of
      vitamin B12 are reviewed. The vitamin B12 application and market are also
      summarized.

PMID- 18807972
TI  - [Progress on hydrogen-production microorganisms by anaerobic fermentation].
AB  - Anaerobic fermentation bio-hydrogen production has captured extensive attention,
      hydrogen-production microorganisms has become the research focus as core role.
      Based on the review of current status and main achievements of hydrogen-producing
      microorganisms research both domestic and abroad, the fermentative type, the
      hydrogen-production capability, the bacterium type, breeding, and the gene
      modification were presented. The main associated issues were analyzed and the
      research prospects were put forward.

PMID- 18807973
TI  - Industrial biosystems engineering and biorefinery systems.
AB  - The concept of Industrial Biosystems Engineering (IBsE) was suggested as a new
      engineering branch to be developed for meeting the needs for science, technology
      and professionals by the upcoming bioeconomy. With emphasis on systems, IBsE
      builds upon the interfaces between systems biology, bioprocessing, and systems
      engineering. This paper discussed the background, the suggested definition, the
      theoretical framework and methodologies of this new discipline as well as its
      challenges and future development.

PMID- 18807974
TI  - [Trend of "zero energy consumption and wastewater" in fuel ethanol production].
AB  - The energy consumption in a Chinese ethanol manufacturer with cassava as the
      feedstock, has been reduced to a zero-closed level. If the R & D on technical
      integration of high ethanol concentration fermentation, methane fermentation
      technique, steam and electricity co-generation system, new distillation
      technology, and the wastewater reutilization, is carried out continuously, the
      proposed "zero energy consumption and wastewater" technique could be realized in
      fuel ethanol production process.

PMID- 18807975
TI  - [Metabolic engineering for improving ethanol fermentation of xylose by wild
      yeast].
AB  - One yeast strain, which was isolated from 256 natural samples, was found to be
      able to utilize D-xylose effectively. On the basis of assimilation physiological
      and molecular biological tests, the yeast strain was identified as a strain of
      Candida tropicalis. Furthermore, metabolic engineering breeding strategy was
      applied to change the metabolic flux in order to increase ethanol productivity.
      In this study, the C. tropicalis was used as the host strain and the plasmid
      pYX212-XYL2, which was formerly constructed for over expression of XYL2 gene
      encoding xylitol dehydrogenase (XDH) from Pichia stipitis, was used as the
      backbone of the recombinant vector. A hygro gene was inserted into downstream
      position of XYL2 gene, meanwhile, the result plasmid pXY212-XYL2-Hygro
      transformed into C. tropicalis by electroporation. Thus, a recombinant yeast C.
      tropicalis XYL2-7 was obtained through hygromycin B resistance screening and its
      specific XDH activity was 0.5 u/mg protein, which was 3 times more than that of
      the parent strain. Additionally, the recombinant yeast was applied in the
      fermentation of xylose. Compared with the parent yeast, it was concluded that the
      xylitol yield in the broth decreased by 3 times, however, the ethanol yield
      increased by 5 times. The feasibility of ethanol production from xylose by C.
      tropicalis was firstly studied in this paper. These research results are helpful
      to advance the bioconversion of renewable resources (e. g. straw, wheat bran, and
      husk) to fuel ethanol.

PMID- 18807976
TI  - [Production of ethanol and isoflavones from steam-pretreated Radix Puerariae by
      solid state fermentation].
AB  - The gelatinization process of the starch is replaced by unpolluted steam
      pretreatment on the base of the Radix Puerariae rich in fiber and isoflavones.
      The production of ethanol and isoflavones by simultaneous saccharification and
      solid state fermentation (SSF) of steam-pretreatment Radix Puerariae is
      presented. The optimal technological conditions were obtained: Radix Puerariae
      being steam-pretreated at a saturated vapor pressure of 0.8 MPa for 3.5 min,
      glucoamylase(65 u/g), cellulase(1.5 u/g), 0.1%(NH4)2SO4, 0.1%KH2PO4 and activated
      yeasts being added in, and fermentation at 35-37 degrees C for 60 h. Under these
      conditions, the yield of ethanol and isoflavones from 100 g Radix Pureriae (dry
      basis) were 27.47 g and 4.43 g, respectively, the starch utilization rate was
      95%. In comparison with the traditional fermentation technology, the simultaneous
      saccharification and SSF of steam-pretreatment Radix Puerariae is clean and
      energy-saving. It provides new way of the production of ethanol from the non-food
      starch material, and worthwhile to be explored and implemented in industry.

PMID- 18807977
TI  - [Global expression profiling of Saccharomyces cerevisiae: metabolic remodeling in
      post-log phase].
AB  - For the purpose of revealing the mechanism of the reduction of yeasts ethanol
      production rate after entrance of post-log phase, we used microarray to study
      expression profiles of the yeast Saccharomyces cerevisiae during the transition
      from mid-log growth phase to post-log growth. The results demonstrate that the
      global pattern of gene expression is very stable during the mid-log phase.
      However, a dramatic metabolic remodeling was found when the yeast entries post
      log phase, during which many of amino acid synthesis and metabolism related genes
      are up-regulated, moreover, ion transport, energy generation and storage related
      genes are also up regulated during this phase, while a large number of genes
      involved in transposition and DNA recombination are repressed. Central metabolic
      pathways also engage in metabolic remodeling, within which the genes involved in
      succinate and a-ketoglutarate synthesis pathways are up regulated, accordance
      with those of amino acid synthesis and metabolism. These results demonstrate that
      the increasing demand for amino acids in post-log phase lead to a metabolic
      transition into TCA cycle and glyoxylate cycle, which subsequently reduce the
      ethanol production rate. This suggests a global insight into the process of yeast
      ethanol fermentation.

PMID- 18807978
TI  - [Gene function and microbial community structure in sulfide minerals bioleaching
      system based on microarray analysis].
AB  - Biohydrometallergy technology received more and more attention because of its
      simple process, low cost and kind to environment, especially in dealing with low
      grade and complex minerals. However, it is difficult to optimize microorganism
      species and process parameters in bioleaching procedure because of the lack of
      suitable bacteria and quantitative analysis methods at micro-level for
      bioleaching system. This has resulted in the low efficiency and poor yield of the
      target metal in bioleaching. With the development of microarray and bacteria
      conservation technology, solutions to the above problems were being found. This
      article summarizes the latest findings on genetic elucidation and the community
      structure of microorganisms in sulfide minerals bioleaching system, in the aim of
      providing a better understanding on the significance of cross-field technology of
      biohydrometallergy and genomics.

PMID- 18807979
TI  - [Screening of cytotoxic activity against B16 tumor cell of mangrove fungi isolate
      from Qinglan harbor in Hainan].
AB  - Six hundred and eight fungi strains were isolated from seventy-eight samples of
      mangrove plants and soil that collected from Qinglan harbor. Cyctotoxic activity
      was detected by observing the growth inhibition or killing of the tumor cells
      under microscope. The result showed that 81 strains (about 13.32% of the total
      strains isolated) displayed cytotoxic activity against B16 tumor cell. The most
      fungi strains were isolated from mangrove plant Sonneratia alba, and most of
      cytotoxic active fungi strains were isolated from mangrove plant Heritiera
      littoralis.

PMID- 18807980
TI  - Towards kinetic modeling of global metabolic networks: Methylobacterium
      extorquens AM1 growth as validation.
AB  - Here we report a systematic method for constructing a large scale kinetic
      metabolic model and its initial application to the modeling of central metabolism
      of Methylobacterium extorquens AM1, a methylotrophic and environmental important
      bacterium. Its central metabolic network includes formaldehyde metabolism, serine
      cycle, citric acid cycle, pentose phosphate pathway, gluconeogensis, PHB
      synthesis and acetyl-CoA conversion pathway, respiration and energy metabolism.
      Through a systematic and consistent procedure of finding a set of parameters in
      the physiological range we overcome an outstanding difficulty in large scale
      kinetic modeling: the requirement for a massive number of enzymatic reaction
      parameters. We are able to construct the kinetic model based on general
      biological considerations and incomplete experimental kinetic parameters. Our
      method consists of the following major steps: (1) using a generic enzymatic rate
      equation to reduce the number of enzymatic parameters to a minimum set while
      still preserving their characteristics; (2) using a set of steady state fluxes
      and metabolite concentrations in the physiological range as the expected output
      steady state fluxes and metabolite concentrations for the kinetic model to
      restrict the parametric space of enzymatic reactions; (3) choosing enzyme
      constants K's and K'(eqS) optimized for reactions under physiological
      concentrations, if their experimental values are unknown; (4) for models which do
      not cover the entire metabolic network of the organisms, designing a dynamical
      exchange for the coupling between the metabolism represented in the model and the
      rest not included.

PMID- 18807981
TI  - [Construction and characterization of a novel somatostatin prokaryotic
      expression].
AB  - In the current work, the fusion gene including somatostatin (SS) and the
      hepatitis B surface antigen gene was cloned into a balanced lethal system plasmid
      (pYA3493), and then transformed into asd- attenuated Salmonella choleraesuis C500
      strain, the positive transformant without antibiotic resistance gene was
      confirmed by restriction analysis and DNA sequencing, designated as pYA-SS. The
      expression and immunogenicity of fusion protein were detected by SDS-PAGE and
      Western blot analysis. These results show that the recombinant prokaryotic
      expression plasmid pYA-SS could express the SS fusion protein with good
      immunogenicity in C500 strain. In above all, this study could provide reliable
      materials to develop novel, good and safe vaccine in enhancing the growth of
      animals.

PMID- 18807982
TI  - [Isolation and fermentation condition of milk-clotting enzyme producing strain
      from glutinous rice wine].
AB  - Glutinous rice wine is a traditional food in south of China and it can coagulate
      milk. It has been proved that its function of coagulating milk is because of the
      presence of milk-clotting enzyme produced by microorganisms in glutinous rice
      wine. The aim of this work is to isolate milk-clotting enzyme producing strain
      from glutinous rice wine and study the fermentation condition. We screened out
      four bacteria and fungus by gradient dilution. It was proved that mold played the
      most important role in the production of milk-clotting enzyme. This is further
      confirmed by casein plate method. The optimization of fermentation conditions
      revealed that two times concentrated potato medium supplemented with 5% glucose
      without additional nitrogen was better for production of the enzyme. The enzyme
      activity was increased 144% under the conditions established.

PMID- 18807983
TI  - [Fusion expression of D-amino acid oxidase from Trignoposis variabilis with
      maltose binding protein and Vitreoscilla hemoglobin].
AB  - D-amino acid oxidase (DAAO) is one of important industrial enzymes. To increase
      the solubility and activity of the TvDAAO from Trignoposis variabilis expressed
      in recombinant Escherichia coli (E. coli), a maltose binding protein (MBP) and
      Vitreoscilla hemoglobin (VHb) was introduced to fuse with N-terminal of the
      TvDAAO, respectively. Fusion protein of MBP-TvDAAO was constitutively expressed
      in JM105/pMKC-DAAO and inductively expressed in JM105/pMKL-DAAO. With respect to
      the control strain of BL21 (DE3)/pET-DAAO without MBP fusion, the constitutive
      fusion expression obtained 28% of soluble protein with 3.7 folds of solubility
      improvement. As for the inductive fusion expression, corresponding results
      changed to 17% and 1.8 folds, respectively. However, the DAAO activity
      significantly decreased in the MBP-fusing expression. Fusion protein of VHb
      TvDAAO was constructed and inductively expressed in BL21 (DE3)/pET-VDAAO. Its
      DAAO activity highly reached 3.24 u/mL in flask culture, about 90% increase in
      contrast to the control without VHb.

PMID- 18807984
TI  - [gTME for construction of recombinant yeast co-fermenting xylose and glucose].
AB  - Global transcription machinery engineering (gTME) was employed to engineer xylose
      metabolism. Mutation of the transcription factor gene Sptl5 was introduced by
      error-prone PCR, followed by screening on media using xylose as the sole carbon
      source. One recombinant strain growing well on such media was chosen for further
      research. This strain showed modest growth rates in the media containing 50 g/L
      xylose or glucose at the condition of 30 degrees C, 200 r/min, 96 h, 94.0% and
      98.9% of xylose and glucose were consumed, with the ethanol yield were 32.4% and
      31.6%, respectively. The control strain had the ethanol yield of 44.3% under the
      glucose concentration of 50 g/L. When the carbon source was 50 g/L glucose/xylose
      (1:1), the utilization ratio of xylose and glucose was 91.7% and 85.9%, with the
      ethanol yield was 26%. Xylose was eventually exhausted. Concentration of the by
      product xylitol was very low.

PMID- 18807985
TI  - [Cloning and characterization of the chloramphenicol resistant gene of Serratia
      marcescens strain KMR-3].
AB  - Chloramphenicol-resistant gene was cloned and analyzed by constructing genomic
      DNA library of Serratia marcescens KMR-3. It showed that cloned chloramphenicol
      resistant gene encoded a protein product of 397 amino acids. The protein belonged
      to PRK10473 protein, and it showed 92% similarity to drug resistance transporter,
      Bcr/CflA subfamily of Serratia proteamaculans 568. Regulation elements including
      promoter, terminator, Shine-Dalgarno (SD) sequence and transcription start site
      also were identified.

PMID- 18807986
TI  - [Technology investigation of extracting fish oil by enzymolysising ocean wild
      fish].
AB  - Compared with cultured fish, the fish oil of ocean wild fish contains much more
      Eicosapntemacnioc acid (EPA), Docosahexenoic acid (DHA), fat-soluble vitamin. To
      improve the utility value of oacean wild fish, small hairtail was used as raw
      material to investigate the technology of extracting fish oil with enzyme. The
      variables to affect the efficiency of extraction, extracting and centrifugation
      were selected as temperature, reaction time and pH value. Optimal technology
      conditions were determined by the response surface method: The liquid/solid ratio
      is 6, pH 7.3, enzyme amount of 1000 u/g raw material, agitation speed of 200
      r/min, enzymolysis under 45 degrees C for 90 min. The optimum extraction
      conditions were as follows: 100 mL extractant (every 20 g surimi), pH4.0,
      extracted under 40 degrees C for 25 min. The optimal centrifuge conditions were:
      centrifuge speed of 3000 r/min (1865 g), centrifuged for 10 min. The oil
      extraction efficiency was 79.9%. This study developed the traditional technology
      of fish oil extraction, and improved the protection of the active components.

PMID- 18807987
TI  - [Purification and characterization of extracellular polysaccharides from Nostoc
      flagelliforme].
AB  - The extracellular polysaccharides (EPS) of N. flagelliforme were purified by DEAE
      anion exchange chromatography and Sephadex G100 gel filtration chromatography.
      And two main components named NFPS1 and NFPS2 were obtained respectively. The
      physico-chemical characteristics of NFPS2 were analyzed and compared with NFPS0,
      which was obtained from field colony of N. flagelliforme. These results showed
      that both of NFPS2 and NFPSO were composed of four monosaccharides: glucose,
      xylose, galactose and mannose. The apparent molecular weight of NFPS2 and NFPS0
      was estimated to be 2.79 x 10(5), 2.26 x 10(5) respectively. They are non
      sulfated polysaccharides, free of protein and nuclear acid. The thermal analysis
      indicated that there was a decomposition peak at 245 degrees C in
      thermogravimetric (TG) curves. However, the microstructure analysis showed that
      they had different porous structures.

PMID- 18807988
TI  - [Enhanced production of curdlan by Alcaligenes faecalis by selective feeding with
      ammonia water during the cell growth phase of fermentation].
AB  - Curdlan is a water insoluble exopolysaccharide produced by Alcaligenes faecalis
      under nitrogen-limiting conditions. After excretion, the polysaccharide is
      attached the cell wall. Thus enhancement of biomass production during the cell
      growth phase is important to curdlan production. A strategy of increasing
      nitrogen source to improve biomass production was adopted for curdlan production
      by Alcaligenes faecalis (ATCC 31749). In the batch fermentation of curdlan, a
      relatively higher NH4Cl level of 3.6 g/L with continuous glucose feeding
      increased the cell density leading to improvement of curdlan production. However,
      excessive NH4Cl would inhibit curdlan production and biomass production was not
      improved significantly. In addition, feeding of ammonia water at the initial
      phase replaced NaOH solution to control pH at 7.0. Subsequently, feeding of NaOH
      solution was resumed to control pH at 5.6 for curdlan production after ammonia
      was consumed. As a result, biomass production and curdlan yield were both
      enhanced remarkably. Feeding of ammonia water during the first 24 h led to
      biomass production of 18.8 g/L. However, higher cell density did not lead to
      increase in curdlan production. The maximum curdlan production (72 g/L) was
      obtained by feeding ammonia water for the first 14 h, during which the cell
      density was about 11.9 g/L.

PMID- 18807989
TI  - [Optimization of culture condition of a moderately thermophilic acidophilic
      Ferroplasma thermophilum].
AB  - The extreme microorganisms Ferroplasma spp., play an important role in
      bioleaching of sulphide ores at low pH value and temperatures around 50 degrees
      C. Without cell wall, Ferroplasma spp. is sensitive to pulp density, shearing
      force and heavy metal ions. Thus it is difficult to obtain their high cell
      density cultures, which limits the large-scale industrial application. In this
      paper, the optimum culture conditions of Ferroplasma thermophilum were studied by
      shaking culture. The results showed that the optimum culture conditions are as
      follows: 50 degrees C, initial pH 0.5, 50 mL working volume in 250 mL shaking
      flask, inorganic nitrogen source (NH4)2SO4. The optimum combination of
      FeSO4.7H2O, yeast extract and peptone was determined by orthogonal experiments,
      including FeSO4.7H2O 40 g/L, yeast extract 0.3 g/L, peptone 0.2 g/L. Under the
      optimum culture conditions, the cell density was up to 6.3 x 10(7) cell/mL, and
      the oxidation of 40 g/L ferrous sulfate heptahydrate was finished in less than 72
      hours. The results might provide information for scale-up of archaeon culture as
      well as its industrial application.

PMID- 18807990
TI  - [Effect of H2O2 stress on glutathione production by Candida utilis].
AB  - Glutathione (GSH) plays an important role in the responses of microorganisms to
      the environmental stimulation and stress. The effect of H2O2 stress under
      different fermentation time and H2O2 concentration as well as continuous stress
      on GSH fermentation of Candida utilis were investigated in this paper. It was
      found that low concentration of H202 accelerated GSH production. When treated by
      low concentration of H2O2 (36 mmol/L), the final concentration of GSH reached 922
      mg/L and the intracellular GSH content reached 1.64%, which increased by 7% and
      35% than the controls, respectively.

PMID- 18807991
TI  - [Environmental factors affecting the succinic acid production by Actinobacillus
      succinogenes CGMCC 1593].
AB  - Actinobacillus succinogenes is a promising candidate for the production of bio
      based succinic acid. Previously, we isolated a succinic acid-producing strain
      Actinobacillus succinogenes CGMCC 1593 from bovine rumen. In this paper, the
      influence of the environmental factors such as gas phase, pH, ORP, on succinic
      acid production by A. succinogenes CGMCC 1593 was studied. The results showed
      that CO2 was the optimum gas phase for anaerobic fermentation ofA. succinogenes
      CGMCC 1593 as well as one of the substrate for the succinic acid synthesis. Using
      MgCO3 as a pH regulator, the pH was maintained within 7.1-6.2 during the
      anaerobic fermentation for the cell growth and acid production of A. succinogenes
      CGMCC 1593. Our results showed that low initial ORP was disadvantageous for the
      growth of A. succinogenes CGMCC 1593 and an ORP of -270 mV was demonstrated to be
      beneficial to the succinic acid production. By adding Na2S.9H2O to decrease ORP
      to -270 mV at the end of exponential growth phase in batch culture of A.
      succinogenes CGMCC 1593, the succinic acid concentration reached 37 g/L and the
      yield of succinic acid was 129% at 48 h. This work might provide valuable
      information for further optimization of succinic acid fermentation by A.
      succinogenes CGMCC 1593.

PMID- 18807992
TI  - [Isolation and identification of polysaccharide from sweet potato vines].
AB  - China is the largest country of cultivating sweet potato in the world. The
      resources of sweet potato vines (SPV) are huge. To exploit the rich resources,
      SPV of XuShu 18 was selected as raw materials since it is cultivated in China
      widely. Polysaccharide from SPV was extracted by pilot instrument and
      precipitated by ethanol. The decolouring technology was studied. By primary
      purification, we obtained the polysaccharide from SPV (PSPV) and studied its
      physical and chemical characters. Using DEAE-cellulose column and NaCl solution
      as eluting reagent, three kinds of pure polysaccharide, named PSPV I, PSPV II and
      PSPVIII respectively, were obtained. Then the molecular weight distribution and
      sugar compositions were studied using High Performance Gel Filtration
      Chromatography and GC. The followings are the results. PSPV I was separated from
      PSPV which was extracted from SPV harvested in the middle of June. Its M.W. is
      6.278 x 10(4) D and is mainly composed of Xylose, Mannose and Glucose. PSPV II
      and PSPVIII were separated from PSPV which was extracted from SPV harvested in
      the middle of October. Their M.W. are 3.801 x 10(4) D and 1.418 x 10(4) D
      respectively. PSPVII is mainly composed of mannose and galactan. PSPVIII is
      mainly composed of glucose, xylose and rhamnose. The results provide theoretical
      basis for the utilization of SPV.

PMID- 18807993
TI  - [Optimization of enzymatic resolution technique of glycidyl butyrate via response
      surface methodology].
AB  - Our previous work has indicated that enzymatic resolution of glycidyl butyrate
      are strongly affected by many factors, including concentration of substrate,
      amount of lipase, the temperature, pH, shaking speed and reaction time. In this
      study, Plackett-Burman design was undertaken to evaluate the effects of the six
      factors. By regression analysis, concentration of substrate, amount of lipase and
      the temperature were found to be important for enzymatic resolution of glycidyl
      butyrate. In the second phase of the optimization process, a response
      surfacemethodology (RSM) was used to optimize the above critical factors, and to
      find out the optimal concentration levels and the relationships between these
      factors. By solving the quadratic regression model equation using appropriate
      statistic methods, the optimal parameter of the variables were determined as:
      0.499 mol/L glycidyl butyrate, 30.23 mg/g lipase and 29.68 degrees C. In the
      optimum condition, the value of enantiomeric excess(ee%) was 93.28%. Compared to
      84.65% which was the maximum ee% under the non-optimized condition, this study
      has a significant advancement. The experimental data under various conditions
      have validated the theoretical values.

PMID- 18807994
TI  - [Optimization of bacterial cellulose fermentation medium and observation of
      bacterial cellulose ultra-micro-structure].
AB  - In order to improve the yield of bacterial cellulose (BC), the fermentation
      medium of BC-producing strain J2 (Gluconobacter) was optimized, and BC ultra
      micro-structure was observed. Initially, Plackett-Burman design was employed to
      evaluate eight variables which were relevant to BC production. Three
      statistically significant parameters including yeast extract, ZnSO4, ethanol were
      selected and other 5 variables were not significant (P > 0.05). The optimized
      levels of three variables were defined by Box-Behnken design and response surface
      methodology (RSM). BC ultra-micro-structure was observed by scanning electron
      microscope (SEM) with cotton cellulose as comparison. The results indicated that
      the BC yield under the optimum fermentation medium was 11.52 g/100 mL, which was
      as 1.35 times as that under the original fermentation medium. The SEM photos
      manifested that bacterial cellulose ribbon, with a diameter less than 0.1 microm,
      was less than cotton cellulose ribbon. The bacteria inside the cellulose net were
      eliminated after the NaOH treatment.

PMID- 18807995
TI  - [Propionic acid fermentation by Propionibacterium freudenreichii CCTCC M207015
      with a fibrous-bed bioreactor].
AB  - The production of propionic acid by Propionibacterium freudenreichii CCTCC
      M207015 was investigated in a Fibrous-bed bioreactor (FBB). The FBB was
      constructed by packing spiral cotton fibrous and immobilized into a bioreactor.
      By applying this bioreactor to propionic acid fermentation, the propionic acid
      yield had a significant improvement and reached 20.41 g/L, compared with the cell
      free culture of 14.58 g/L (40 g/L of glucose). At the same time, the glucose
      exhausting time decreased from 120 h to 60 h. Batch fermentations at various
      glucose concentrations were carried out with FBB. Based on the analysis of the
      time course of production, fed-batch fermentation was also applied to produce
      propionic acid with FBB, the maximal propionic acid yield reached 45.91 g/L, and
      the proportion of propionic acid to total acids was about 72.31%.

PMID- 18807996
TI  - [Denitrogenation of petroleum by a Pseudomonas sp].
AB  - Biodenitrogenation of petroleum oil was investigated by a previously isolated
      carbazole-degrader Pseudomonas sp. XLDN4-9. In a tetradecane-aqueous phase
      system, biodegradation of carbazole was enhanced by the presence of n
      tetradecane. And strain XLDN4-9 was capable of absorbing 95.2% of 2 g/L carbazole
      dissolved in diesel within 15 hours. Significant denitrogentation of crude oil,
      diesel and lubricanting oil was detected by strain XLDN4-9. Removal of carbazole,
      methylcarbazole, and dimethylcarbazole in diesel was confirmed by using GC-MS.
      After 3 days, 99% of carbazole and 15% of dimethyl carbazole was degraded. And
      the removal rate of 1-, 2-, 3-, and 4-methyl carbazole was determined to be
      63.4%, 87.6%, 78.4%, and 66.5% respectively.

PMID- 18807997
TI  - [Conversion of corncob into biohydrogen by anaerobic fermentation].
AB  - Biohydrogen production from corncob by dark fermentation was reported for the
      first time. The effects of the pretreatment condition, substrate concentration
      and initial pH on the hydrogen production were investigated in batch
      cultivations. The maximum hydrogen yield of 107.9 mL/g-TVS and hydrogen
      production rate of 4.2 mL/g-TVS .h(-) were obtained under the condition of 1% HCl
      pretreating substrate for 30 min, 10 g/L substrate concentration and initial
      pH8.0. The content of hemicellulose in corncob decreased significantly from 42.2%
      to 3.0% after HC1 pretreatment. The contents of cellulose, hemicellulose and
      lignin in the acid pretreated corncob decreased slightly in hydrogen producing
      process. The results indicate that the acid pretreatment of the substrate plays a
      key role in the conversion of corncob into biohydrogen. Fourier transform
      infrared spectroscopy (FTIR) was used to study the changes in the corncob
      composition during the treatment of chemical-microbial process. It was shown that
      the amorphous domains of cellulose and hemicellulose were hydrolyzed into
      fermentable asccharides through HCl pretreatment and the microorganisms had a
      devastating effect on the crystallinitiy of the cellulose.

PMID- 18807998
TI  - [Inactivation mechanism of microorganisms by the synergy of silver and light
      irradiation, and the application in household electrical appliances].
AB  - The inactivation efficiencies of microorganisms were found to be enhanced by
      using silver solution together with ultraviolet light (UV-A, 395 nm) irradiation.
      The inactivation efficiencies were improved remarkably especially in eukaryotic
      microorganism. To make clear the inactivation mechanism of microorganisms by the
      combination effect of silver and ultraviolet light irradiation, the resultant
      solution was characterized by ESR (Electron spin resonance, ESR). Scanning
      electron microscopy (SEM) and the methnd for measuring enzyme activity of
      mitochondria for eukarvotic cells were used to conjecture the mechanism, by
      analysis of the morphological and physiologic changes in eukaryotic cells. It is
      proposed that silver oxide (Ag20) can be activated by ultraviolet light
      irradiation and react with water molecules to produce hydroxyl radical (.OH).
      Hydroxyl radical could damage cell wall of eukaryotic microorganisms, and
      inactivate the enzyme activity of mitochondria of eukaryotic microorganism cells.
      Accordingly, eukaryotic microorganism cells would die. In the experiment,
      Staphylococcus aureus was employed as the representative of prokaryotic
      microorganisms, and Candida albicans and Trichophyton mentagrophytes as the
      representative of eukaryotic microorganisms, respectively. Moreover, the results
      of the technology applied to washing machine were presented and discussed.

PMID- 18807999
TI  - [1, 3-propanediol production under salt stress].
AB  - Through studying the process of glycerol fermentation to 1, 3-propanediol(1, 3
      PD) by Klebsiella pneumoniae, it was found that the cell growth and product (or
      by-product) production were under salt stress. Cell growth and product formation
      kept high rate at low salt concentration. High salt concentration led to low
      growth of cells, final concentration of 1, 3-PD and conversion from glycerol to
      1, 3-PD, and, 1, 3-propanediol oxidoreductase activity decreased. When the salt
      concentration in 5 m3 bioreactor was controlled under appropriate manner, the
      concentration of 1, 3-PD production was markedly enhanced. The final 1, 3-PD
      concentration ,the conversion of glycerol to 1, 3-PD and productivity were 64
      g/L, 61% and 2.1 g/(L x h).

PMID- 18808000
TI  - [A novel strain ZG0656 producing alpha-amylase inhibitor and fermentation,
      separation, properties, and application of its products].
AB  - A strain ZG0656 producing a-amylase inhibitor was isolated from soil in this
      study. Polyphasic taxonomic studies were performed, including appearance
      characteristics, culture characteristics, phenotypic characteristics, cell walls
      chemical composition, nearly complete 16S rDNA sequence alignment with those of
      representative Streptomyces species. These results revealed that strain ZG0656
      represents a novel variation of Streptomyces coelicoflavus, for which we propose
      the name S. coelicoflavus var. nankaiensis. After fermentation in a 10 L
      fermentor, alpha-amylase inhibitors were accumulated in the harvested broth of
      strain ZG0656. The alpha-amylase inhibitors we obtained were identified as
      aminooligosaccharides after concentration, resin-adsorption, gel-filtration, and
      desiccation. They could intensively inhibit alpha-amylase, depress postprandial
      blood glucose elevation obviously. Thus, the a-amylase inhibitors are expected to
      act as drugs or functional food against diabetes.

PMID- 18808001
TI  - [Mutational research on the role of lysine 21 in the Pichia stipitis xylose
      reductase].
AB  - The xylose reductase of Pichia stipitis is one of the most important enzymes. It
      can be used to build up recombinant Saccharomyces cerevisiae strain for utilizing
      xylose and producing ethanol. Intercellular redox imbalance caused by NADPH
      preference over NADH for Pichia stipitis xylose reductase (PsXR) has been
      considered to be one of the main factors for poor ethanol productivity. Some key
      amino acids of PsXR, which affect the activity or coenzyme preference, were
      investigated in our previous study. In this study, Lys21 were rational designed
      for site-directed mutagenesis to alter coenzyme specificity of PsXR from NADPH
      and NADH into single NADH. The wild gene and mutagenesis genes were ligated into
      pET28b, and were transferred into E.coli BL21(DE3). After induced by IPTG, the
      xylose reductases were purified. Purified mutants K21A (Lys21-->Ala), K21R(Lys21-
      >Arg) were characterized by steady-state kinetic analysis. The results showed
      that the coenzyme dependence of K21A was completely reversed to NADH.

PMID- 18808002
TI  - [Screening, identifying of cellulose-decomposing strain L-06 and its enzyme
      producing conditions].
AB  - Cellulases are relatively costly enzymes that are sold in large volumes for use
      in different industrial applications, and a significant reduction in cost will be
      important for their commercial use in biorefineries. The production of cellulase
      is a major factor in the hydrolysis of cellulosic materials. Hence it is
      essential to make the process economically viable. A strain (L-06) with high
      cellulase activity was screened from rice straw compost and classified as
      Penicillium decumbens by the analysis of its morphology and 18S rRNA gene
      sequences. Different conditions of liquid fermentation medium including nitrogen
      source, carbon source, surfactant, temperature, initial pH, inoculation quantity
      for the production of cellulase had been studied. The maximal beta-1, 4
      glucosidase(BGL) activity was 1662 u/mL which is 1.49 times of the previous and
      the maximal exo-beta-1, 4-glucanases(CBH) activity was 2770 u/mL which is 1.36
      times of the previous, cultured in the optimal condition for three days. And the
      maximal endo-beta-1, 4-glucanases (EG) activity was 18064 u/mL which is 1.87
      times of the previous and the maximal filter paper enzyme(FPase) activity was
      4035 u/mL which is 1.47 times of the previous, cultured in the optimal condition
      for four days. In the optimization experiments, the EG and CBH in the culture
      condition (pH10) maintained 70% and 43% activity. In the culture condition (50
      degrees C) EG and CBH maintained 59% and 68% activity, which showed heat and
      alkali resistant characteristics.

PMID- 18808003
TI  - [The high ethanol tolerance in a thermophilic bacterium Anoxybacillus sp. WP06].
AB  - Anoxybacillus sp. WP06 is a thermophilic (optimum temperature for growth, 60
      degrees C), facultative anaerobe. Strain WP06 is able to utilize a wide range of
      carbon sources such as glucose, xylose, arabinose, starch, maltose and sorbitol.
      Anaerobically, glucose and xylose were fermented to ethanol as minor products.
      Unlike most thermophilic bacteria isolated to date, strain WP06 is tolerant
      (maintained viability) to high ethanol concentrations up to 15% at 60 degrees C.
      The growth rate was slightly inhibited at 8% ethanol. The observation that strain
      WP06 exhibits higher tolerance of 15% ethanol at 60 degrees C exploits the level
      of ethanol tolerance in thermophilic bacteria. Strain WP06 may be candidate for
      mechanisms of ethanol tolerance in thermophilic bacteria.

PMID- 18808004
TI  - [Simulation of three-dimensional green biomass of urban forests in Shenyang City
      and the factors affecting the biomass].
AB  - Based on the fractal theory of forest growth, stepwise regression was employed to
      pursue a convenient and efficient method of measuring the three-dimensional green
      biomass (TGB) of urban forests in small area. A total of thirteen simulation
      equations of TGB of urban forests in Shenyang City were derived, with the factors
      affecting the TGB analyzed. The results showed that the coefficients of
      determination (R2) of the 13 simulation equations ranged from 0.612 to 0.842. No
      evident pattern was shown in residual analysis, and the precisions were all
      higher than 87% (alpha = 0.05) and 83% (alpha = 0.01). The most convenient
      simulation equation was ln Y = 7.468 + 0.926 lnx1, where Y was the simulated TGB
      and x1 was basal area at breast height per hectare (SDB). The correlations
      between the standard regression coefficients of the simulation equations and 16
      tree characteristics suggested that SDB was the main factor affecting the TGB of
      urban forests in Shenyang.

PMID- 18808005
TI  - [Effects of silicon on photosynthetic characteristics of Indocalamus barbatus
      under simulated acid rain stress].
AB  - With Indocalamus barbatus as test material, the effects of silicon on the
      relative content of chlorophyll, diurnal variations of photosynthesis, and
      chlorophyll fluorescence were examined under simulated acid rain (pH 3.0) stress.
      The results showed that under acid rain stress, 20 and 500 mg x L(-1) of Na2SiO3
      could prohibit the decrease of the relative content of chlorophyll to some
      extent; 100 mg x L(-1) of Na2SiO3 could get best effect, with the relative
      chlorophyll content being 22.7% higher than the control; while 500 mg x L(-1) of
      Na2SiO3 didn't have any effect. Under the stress, the midday depression of
      photosynthesis became more serious. The average daily net photosynthetic rate
      (Pn), stomatal limitation value (Ls), and stomata conductance (Gs) were all
      decreased significantly, while the intercellular CO2 concentration (Ci)
      increased. After treated with 20-100 mg x L(-1) of Na2SiO3, the Pn, Ls, and Gs
      increased to some extent while Ci decreased, and 100 mg x L(-1) of Na2SiO3 was
      most effective, with the average daily Pn increased by 39.2%. The maximum
      fluorescence of dark adaptation (Fm), maximal photochemical efficiency (Fv/Fm),
      potential activity (Fv/Fo), effective photochemical efficiency (Fv'/Fm'), maximum
      fluorescence of light adaptation (Fm') of PSII, photochemical quenching (qp), non
      photochemical quenching (qN), and actual photochemical efficiency of PSII
      (PhiPSII) were all decreased obviously under simulated acid rain stress, but the
      minimum fluorescence of dark adaptation (Fo) and the minimum fluorescence of
      light adaptation (Fo') increased. 100 mg x L(-1) of Na2SiO3 could restrain the
      changes of fluorescence parameters obviously, with the Fv/Fm, Fv/Fo, Fv'/Fm' and
      PhiPSII increased by 35.2%, 146.2%, 55.0% and 24.3%, respectively, compared with
      the control. It was suggested that applying appropriate concentration of
      exogenous silicon to I. barbatus could efficiently relieve the decrease of its
      photosynthetic activity and the damage of its photosynthetic system caused by
      acid rain, and thus, improve its photosynthetic ability under the stress.

PMID- 18808006
TI  - [Response processes of Aralia elata photosynthesis and transpiration to light and
      soil moisture].
AB  - By using CIRAS-2 portable photosynthesis system, the light response processes of
      Aralia elata photosynthesis and transpiration under different soil moisture
      conditions were studied, aimed to understand the adaptability of A. elata to
      different light and soil moisture conditions. The results showed that the
      response processes of A. elata net photosynthetic rate (Pn), transpiration rate
      (Tr), and water use efficiency (WUE) to photon flux density (PFD) were different.
      With the increasing PFD in the range of 800-1800 micromol x m2(-2) x s(-1), Pn
      changed less, Tr decreased gradually, while WUE increased obviously. The light
      saturation point (LSP) and light compensation point (LCP) were about 800 and 30
      micromol m(-2) x s(-1), respectively, and less affected by soil water content;
      while the apparent photosynthetic quantum yield (Phi) and dark respiratory rate
      (Rd) were more affected by the moisture content. The Pn and WUE had evident
      threshold responses to the variations of soil water content. When the soil
      relative water content (RWC) was in the range of 44%-79%, A. elata could have
      higher levels of Pn and WUE.

PMID- 18808007
TI  - [Heavy metals contents and Hg adsorption characteristics of mosses in virgin
      forest of Gongga Mountain].
AB  - Seven main moss species in the Hailuogou virgin forest of Gongga Mountain were
      sampled to determine their heavy metals (Hg, Cr, Cd, Ni, Pb, Cu, Mn, Zn and Fe)
      content, and two widely distributed species, Pleurozium schreberi (Brid.) Mitt.
      and Racomitrium laetum Besch., were selected to study their Hg adsorption
      characteristics. The results showed that the heavy metals contents in the mosses
      were lower than the background values in Europe and America, except that the Cd
      had a comparable value, which indicated that the atmosphere in study area was not
      polluted by heavy metals and good in quality. The Hg adsorption by P. schreberi
      and R. laetum was an initiative and rapid process, with the equilibrium reached
      in about two hours, and could be well fitted by Freundlich and Langmuir
      equations. Based on Langmuir equation, the maximum Hg adsorption capacities of P.
      schreberi and R. laetum were 15.24 and 8.19 mg x g(-1), respectively, suggesting
      that the two mosses had a good capacity of Hg adsorption, and could be used as
      the bio-monitors of atmospheric Hg pollution.

PMID- 18808008
TI  - [Effects of artificial Ulmus pumila forest on plant diversity of temperate
      grassland in Inner Mongolia].
AB  - Based on field survey, the effects of artificial Ulmus pumila forest on the
      species diversity of temperate grassland in Siziwang Banner of Inner Mongolia
      were studied. The results showed that U. pumila forest had obvious effects on the
      species diversity of grassland. With increasing density of U. pumila, the
      Patrick's richness, Pielou's evenness and Shannon-Wiener index of grass species
      under the forest had a decreasing trend, and were higher nearby the forest than
      far from the forest. The habitat inside the forest was favorable to Silene
      jenisseensis, while that nearby the forest was favorable to Heteropappus
      altaicus, Pocockia ruthenia, Potentilla bifurca, Leymus secalinus and
      Cleistogenes squarrosa, suggesting that to blindly exclude forestation on
      grassland could be less scientific, while properly afforesting U. pumila on the
      sides with relatively abundant soil moisture should be available to the
      conservation of plant diversity in temperate grassland regions.

PMID- 18808009
TI  - [Effects of bio-mulching on rhizosphere soil microbial population, enzyme
      activity and tree growth in poplar plantation].
AB  - Coriaria nepalensis, Pteridium aquilinum var. latiuscukum, Imperata cylindrical
      var. major, and Quercus fabric were used as mulching materials to study their
      effects on the rhizosphere soil microbial population and enzyme activity and the
      tree growth in poplar plantation. The results showed that after mulching with
      test materials, the populations of both bacteria and fungi in rhizosphere soil
      were more than those of the control. Of the mulching materials, I. cylindrical
      and Q. fabric had the best effect, with the numbers of bacteria and fungi being
      23.56 and 1.43 times higher than the control, respectively. The bacterial and
      fungal populations in rhizosphere soil increased with increasing mulching amount.
      When the mulching amount was 7.5 kg m(-2), the numbers of bacteria and fungi in
      rhizosphere soil were 0.5 and 5.14 times higher than the control, respectively.
      Under bio-mulching, the bacterial and fungal populations in rhizosphere soil had
      a similar annual variation trend, which was accorded with the annual fluctuation
      of soil temperature and got to the maximum in July and the minimum in December.
      The urease and phosphatase activities in rhizosphere soil also increased with
      increasing mulching amount. As for the effects of different mulching materials on
      the enzyme activities, they were in the order of C. nepalensis > P. aquilinum >
      I. cylindrical > Q. fabric. The annual variation of urease and phosphatase
      activities in rhizosphere soil was similar to that of bacterial and fungal
      populations, being the highest in July and the lowest in December. Bio-mulching
      promoted the tree height, DBH, and biomass of poplar trees significantly.

PMID- 18808010
TI  - [Coupling effects of water and chemical fertilizers on Hevea brasiliensis latex
      yield].
AB  - Water and nutrient are the two main factors limiting Hevea brasiliensis growth
      and its latex yield. With 17 year-old Clone SCATC 7-33-97 H. brasiliensis as test
      material, the coupling effects of water and chemical N, P and K fertilizers on
      latex yield were studied by general orthogonal rotation design of quadratic
      regression with four factors and five levels under field condition, and a
      regressive mathematical model was set up based on the latex yield by quadratic
      regression analysis. The results showed that all test coupling levels of water
      and chemical fertilizers had significant effects on the latex yield. The yield
      increasing effect of test factors was in the order of N application rate >
      irrigation amount > P application rate > K application rate, while the coupling
      effect of water and chemical fertilizers was in the sequence of water and N > N
      and P > water and P > water and K. There was a negative coupling effect of K
      application rate and soil moisture content. For latex yield, the optimum
      application rates of chemical fertilizers were 476.39 kg x hm(-2) of urea, 187.70
      kg x hm(-2) of superphosphate and 225.77 kg x hm(-2) of potassium chloride, and
      the optimum irrigation amount was to have 82.78% soil relative water content.

PMID- 18808011
TI  - [Dynamics of initial decomposition of Calamagrostis angustifolia litter in
      Sanjiang Plain of China].
AB  - A 28-day leaching-decomposition experiment was conducted to study the effects of
      microbial activity and leaching on the initial decomposition of Calamagrostis
      angustifolia litters taken from the boggy meadow and meadow in Sanjiang Plain of
      China. The results showed that the mass loss of the litters at their initial
      decomposition stage accounted for 59% and 22% of yearly mass loss, respectively,
      and the remaining dry mass decreased significantly after 28-day decomposition. By
      the end of the experiment, the N content in the litters decreased by 32.65% and
      24.55% , and P content decreased by 36.71% and 45.15%, respectively. The N and P
      contents in the litters treated with chloroform were higher than those of the
      control, but the difference was not significant. No significant difference was
      also observed in the N and P release from the litters to the leachates between
      the treatment of chloroform and CK, which indicated that the initial
      decomposition of the litters was mainly affected by leaching. There was no
      significant difference in the decomposition rate and nutrient loss rate between
      the two litters.

PMID- 18808012
TI  - [Monthly dynamics and distribution of major cations in Iris lactea].
AB  - The study on the monthly absorption, transportation, and distribution of Na+, K+,
      Ca2+ and Mg2+ in Iris lactea under saline-alkali field conditions showed that the
      contents of test cations in I. lactea varied with months. After June, the cations
      contents in plant increased with growth. Root Ca2+ and Na+ contents were the
      highest in July, being 2.30% and 0.51%, respectively, while root K+ and Mg2+
      contents were the highest in September (0.27%) and October (0.28%), respectively.
      Leaf Na+ content was the highest in July (0.57%), while leaf K+, Ca2+ and Mg2+
      contents were the highest in August, being 1.30%, 2.69% and 0.47%, respectively.
      In July and August, the selective absorption (SA) of K+ was higher than that of
      Na+, while the selective transport (ST) was in adverse. The cations contents in
      I. lactea were significantly higher than those in soil, suggesting that I. lactea
      had high accumulation capacity to these cations. The cations were mainly
      accumulated in the 0-30 cm aboveground part and 0-40 cm underground part of I.
      lactea, and the average contents of Na+, K+, Ca2+ and Mg2+ in aboveground part
      were 9.11, 4.07, 0.98 and 2.27 times of those in underground part, respectively.

PMID- 18808013
TI  - [Effects of waterlogging on ecophysiological characteristics of Salix variegate
      seedlings].
AB  - Salix variegate, a widely distributed species along the riverbank in Three Gorges
      Reservoir area, plays an important role in soil conservation and riverbank
      stabilization. Waterlogging from April to May was simulated in 2006 to test the
      adapting ability and mechanism of S. variegate seedlings to water environment
      change resulted from the construction of Three Gorges Project. The results showed
      that under waterlogging, all of the S. variegate seedlings could survive, but
      their maximum photosynthesis (Pmax), transpiration rate (Tr), water use
      efficiency (WUE), and stomatal conductance (Gs) decreased significantly with the
      prolongation of waterlogging. In the early period of waterlogging (20 days),
      these indices changed little, with the Pmax and Tr decreased by 18.5% and 2.2%,
      respectively, compared with the control. After 30 days, Pmax and Tr decreased by
      53.4% and 23.7%, respectively, and then, kept stable. The contents of chlorophyll
      and carotenoid and their ratio decreased significantly with the prolongation of
      waterlogging, while the ratio of chlorophyll a to b increased significantly. The
      ratio of chlorophyll to carotenoid ranged in 4.873-6.883, and that of chlorophyll
      a to b ranged in 2.855-3.912. Adventitious roots were developed after
      waterlogging, which would benefit the oxygen supply for the plants. It was
      suggested that S. variegate had good adaptability to waterlogging, and could be
      used as a pioneer species in the restoration of degraded water-level fluctuation
      zone.

PMID- 18808014
TI  - [Dynamic changes of soil moisture in loess hilly and gully region under effects
      of different yearly precipitation patterns].
AB  - Based on field determinations, the dynamic changes of soil moisture in dry
      farmland, Robinia pseudoacacia forestland, Hippophae shrubland and Bothriochloa
      ischaemum grassland in loess hilly and gully region under effects of different
      yearly precipitation patterns were analyzed. The results showed that yearly
      precipitation pattern had definite effects on the seasonal variation and profile
      distribution of soil moisture. In normal year, soil moisture in dry farmland had
      a gentle seasonal variation; in dry year, it decreased slowly before rainy season
      but increased markedly after rainy season; while in rainy year, it had an overall
      increase and the increment was remarkable after rainy season. The soil moisture
      in R. psendoacacia forestland, Hippophae shrubland, and B. ischaemun grassland
      decreased as a whole in normal year. In dry year, soil moisture in Hippophae
      shrubland decreased first and increased then, while that in R. psendoacacia
      forestland and B. ischaemun grassland varied in "W" type, with the minimum in
      June and August. In rainy year, the seasonal variation of soil moisture in R.
      psendoacacia forestland and Hippophae shrubland presented "V" type, and that in
      B. ischaemu grassland fluctuated markedly, with the minimum in August. In dry
      farmland, the active and sub-active layers of soil moisture were deeper in dry
      year than in normal year, and the sub-active layer disappeared in rainy year. In
      R. psendoacacia forestland and B. ischaemu grassland, the active layer of soil
      moisture was deeper in dry and rainy years than in normal year; while in
      Hippophae shrubland, this active layer was shallower in dry and rainy years than
      in normal year.

PMID- 18808015
TI  - [Spatiotemporal variation of soil moisture in a small watershed of loess hilly
      region].
AB  - Based on field determinations, the spatiotemporal variation of soil moisture
      content in a small watershed of loess hilly region from 2002 to 2005 was studied,
      with the main affecting factors analyzed. The results showed that in the study
      area, the mean annual soil moisture profile was in an inverse L shape, with the
      lowest value at the depth of 1 m. The soil moisture contents between the layers
      of 0-0.2 m and below 2.4 m in different years, and those between the layers of 0
      0.2 m and 1.0-2.4 m in different seasons were significantly different. In drought
      years, the lack of precipitation increased the spatial heterogeneity of soil
      moisture content in the layers of 1.0-2.4 m and below 2.4 m significantly; while
      in rainy years, the supplement of precipitation decreased the spatial
      heterogeneity of soil moisture content in 0-0.2 m layer, but had less effects on
      that in the layers of 1.0-2.4 m and below 2.4 m. Slope aspect and land use were
      the two main factors affecting the spatiotemporal variation of soil moisture
      content, while slope position had less effects. In drought years or by the end of
      drought season, the effects of slope aspect on soil moisture content decreased,
      while those of land use type increased with soil depth. In rainy years or by the
      end of rainy season, slope aspect became the most important affecting factor,
      while land use type only affected upper soil layer.

PMID- 18808016
TI  - [Light environment characteristics in maize-soybean strip intercropping system].
AB  - Observations on the light environment characteristics in maize-soybean narrow
      stnp intercropping system were made in 2006 and 2007 to study the spatial
      distribution of photosynthetically active radiation (PAR) in intercropped crop
      canopy, and to analyze the effects of light environment on crop biomass. The
      results indicated that in early growth period, the light transmittance at the
      bottom of the edge rows of soybean strips adjacent to maize was higher than that
      of the inner rows of soybean strips, while it was in adverse for maize strips.
      The horizontal variation of light transmittance at the bottom of crop canopy did
      not vary significantly at reproductive stage, and the average light transmittance
      was less than 7%. In soybean strips, the daily photosynthetic photon flux density
      (PPFD) above inner rows canopy in early growth period was 10% higher than that
      above edge rows canopy, and the average light transmittance of edge rows and
      inner rows in 1: 3 intercropping system (treatment I1) was about 15% higher than
      that in 2:3 system (treatment I2), indicating that the shading of maize strips on
      soybean strips was more senous in treatment I2 than in treatment I1. After
      flowering, there was a significant difference in the daily PPFD between inner
      rows and edge rows of soybean strips, but no significant difference was observed
      between edge rows. The mean light transmittance of edge rows and inner rows of
      soybean strips was 27% and 38%, respectively, and there was no significant
      difference between treatment I1 and treatment I2, which indicated that the
      shading effects of maize strips on soybean strips in treatment I1 and treatment
      I2 were similar at reproductive stage. The biomass of inner rows of soybean
      strips was larger than that of edge rows, and there was no significant different
      between edge rows, indicating that under adequate irrigation, the effects of
      different narrow strip intercropping systems on crop biomass were primarily due
      to the changes of light environment.

PMID- 18808017
TI  - [Evolution characteristics of flag leaf photosynthesis and grain yield of wheat
      cultivars bred in different years].
AB  - Taking six winter wheat (Triticum aestivum) cultivars, i. e., 'Wangshuibai' and
      'Bima 1' bred in 1950s, 'Zhengyin 1' and 'Yangmai 1' bred in 1970s, and 'Yumai
      34' and 'Ningmai 9' bred in 1990s, as test materials, field experiments were
      conducted to study the evolution characteristics of their flag leaf
      photosynthesis and grain yield. The results showed that compared with those bred
      in 1950s and 1970s, the cultivars bred in 1990s had higher chlorophyll content,
      net photosynthetic rate (Pn), PS II maximum photochemical efficiency (Fv/Fm),
      actual photochemical efficiency (PhiPSII), photochemical quenching coefficient
      (qp) and non-photochemical quenching coefficient (qN) at grain-filling stage,
      their flag leaf had a longer functional duration and senesced slower, and their
      harvest indices were higher, with the grain yield increased by 25.90% and 11.29%,
      respectively. It was suggested that in the evolution process of wheat cultivars
      from 1950s to 1990s, the improved photosynthetic capacity and the lengthened
      functional duration of flag leaf after anthesis were the key physiological bases
      for grain yield enhancement.

PMID- 18808018
TI  - [Hyperspectral remote sensing diagnosis models of rice plant nitrogen nutritional
      status].
AB  - The correlations of rice plant nitrogen content with raw hyperspectral
      reflectance, first derivative hyperspectral reflectance, and hyperspectral
      characteristic parameters were analyzed, and the hyperspectral remote sensing
      diagnosis models of rice plant nitrogen nutritional status with these remote
      sensing parameters as independent variables were constructed and validated. The
      results indicated that the nitrogen content in rice plant organs had a variation
      trend of stem < sheath < spike < leaf. The spectral reflectance at visible light
      bands was leaf < spike < sheath < stem, but that at near-infrared bands was in
      adverse. The linear and exponential models with the raw hyperspectral reflectance
      at 796.7 nm and the first derivative hyperspectral reflectance at 738.4 nm as
      independent variables could better diagnose rice plant nitrogen nutritional
      status, with the decisive coefficients (R2) being 0.7996 and 0.8606,
      respectively; while the model with vegetation index (SDr - SDb) / (SDr + SDb) as
      independent variable, i. e., y = 365.871 + 639.323 ((SDr - SDb) / (SDr + SDb)),
      was most fit rice plant nitrogen content, with R2 = 0.8755, RMSE = 0.2372 and
      relative error = 11.36%, being able to quantitatively diagnose the nitrogen
      nutritional status of rice.

PMID- 18808019
TI  - [Soil N2O flux and its affecting factors under different land use patterns in
      Three Gorges Reservoir Area of China].
AB  - By using static chamber techniques, the N2O emission from soils under different
      land use patterns was measured. The results showed that the N2O flux ranged from 
      21 to 435 microg x m(-2) h(-1), and the annual N2O flux was decreased in the
      order of vegetable field > orchard > upland > upland transferred from paddy field
      > woodland, being 447.14, 313.57, 167.00, 124.875 and 7.24 mg x m(-2),
      respectively. The N2O flux presented significant seasonal fluctuation, with the
      maximum in spring and summer, followed by in autumn, and the minimum in winter,
      which was approximately consistent with the changes of air- and soil temperature.
      N2O flux had significant positive correlation with the soil temperature at 5 cm
      depth and soil NO3(-)-N content, but no significant correlation with soil
      moisture and NH4(+)-N contents.

PMID- 18808020
TI  - [N2O emission from rice-rapeseed rotation system in Chengdu Plain of Sichun
      Basin].
AB  - By using static chamber/gas chromatograph techniques, the N2O emission from rice
      rapeseed rotation system in Chengdu Plain of Sichuan Basin was measured from June
      2005 to June 2006, with its characteristics and affecting factors investigated.
      The results showed that the total emission of N2O in a rotation cycle was (8.3 +/
      2.8) kg x hm(-2) x a(-1), and the emission in rice season, rapeseed season and
      fallow season accounted for 30%, 65%, and 5% of the total, respectively. In rice
      season, the mean N2O flux was higher during alternative drainage and irrigation
      than during continuous flooding and drainage, and was roughly the same during
      continuous flooding and drainage. N application was the main driving factor for
      the appearance of N2O emission peak, and the lower moisture content in surface
      soil layer in rapeseed season and fallow season was the main cause inducing soil
      N2O absorption. Soil moisture, soil temperature, N application, and crop
      involvement affected the N2O emission to various extents, and soil moisture was
      the key factor affecting the N2O emission. To avoid the high frequency of dry and
      wet alternation in rice season or to regulate soil moisture content to a level of
      50%-70% WFPS (percentage of water-filled pore space) in rapeseed season and
      fallow season could effectively decrease the N2O emission from the rice-rapeseed
      rotation system.

PMID- 18808021
TI  - [Effects of elevated carbon dioxide and ozone on the growth and secondary
      metabolism of spring wheat].
AB  - With open-top chamber (OTC), the effects of elevated CO2 (550 micromol x mol(-1))
      and O3 (80 nmol x mol(-1)) and their combination on the biomass, total phenols,
      and flavone at different growth stages of spring wheat, as well as the yield
      components at maturity stage, were studied. The results showed that under
      elevated CO2, the biomass and yield components were significantly higher than
      those under ambient CO2 (342 micromol x mol(-1)), while under elevated O3, these
      parameters were significantly lower than those under ambient O3 (30 nmol x mol(
      1)). The combination of elevated CO2 and O3 was at the intermediate place,
      indicating that CO2 could mitigate the negative effects of O3, while O3 could
      weaken the positive effects of CO2. Elevated CO2 and O3 increased the content of
      total phenols in wheat leaves, and the combination of elevated CO2 and O3 had the
      greatest effect. However, at late growth stage, the increment of total phenols
      was decreased. At early growth stage, the total content of leaf flavone under
      elevated CO2 and O3 and their combination was lower than the control, but at
      maturing stage, it was in adverse.

PMID- 18808022
TI  - [Effects of different irrigation patterns on the growth of maize root hair].
AB  - With split-root pot experiment and using optical and electrical microscopes, the
      growth of root hair of maize under different irrigation patterns, i. e. ,
      irrigated on both halves of the pot (conventional irrigation, CI), on one half
      only (fixed partial root zone irrigation, FPRI), and on both halves alternatively
      (alternate partial root zone irrigation, APRI), was observed. The observation
      after 40 days of treatment showed that in non-irrigated root zone of FPRI, the
      length proportion of root covered by vestigial root hairs was 20.96%, being
      higher than that in other zones. In addition to some bletting spots, the root
      system in irrigated zone of FPRI turned yellow, root-branching deteriorated to
      some extent, and the root hair density on the section with thick root hairs was
      lower than that in non-irrigated zone. However, both the length proportion of
      root covered by vestigial root hairs (15.72%) and the deterioration of root hair
      were lower than those in non-irrigated zone. As for CI, the root appearance and
      root hair growth were similar to those of the FPRI irrigated zone. As for the
      early and late irrigated root zones of APRI, the root hair density on the section
      with thick root hairs was high. The length proportion of root covered by
      vestigial root hairs was 9.77% and 10.38% for these two root zones, respectively,
      being lower than that in any root zones of FPRI and CI. It was suggested that
      alternative partial root zone irrigation was more beneficial to the growth of
      root hair than fixed partial root zone irrigation and conventional irrigation.

PMID- 18808023
TI  - [Estimation models of vegetation fractional coverage (VFC) based on remote
      sensing image at different radiometric correction levels].
AB  - The images of post atmospheric correction reflectance (PAC), top of atmosphere
      reflectance (TOA), and digital number (DN) of a SPOT5 HRG remote sensing image of
      Nanjing, China were used to derive four vegetation indices (VIs), i. e.,
      normalized difference vegetation index (NDVI), transformed vegetation index
      (TVI), soil-adjusted vegetation index (SAVI), and modified soil-adjusted
      vegetation index (MSAVI), and 36 VI-VFC relationship models were established
      based on these VIs and the VFC data obtained from ground measurement. The results
      showed that among the models established, the cubic polynomial models based on
      NDVI and TVI from PAC were the best, followed by those based on SAVI and MSAVI
      from DN, with the accuracy being slightly higher than that of the former two
      models when VFC > 0.8. The accuracy of these four models was higher in middle
      densely vegetated areas (VFC = 0.4-0.8) than in sparsely vegetated areas (VFC = 0
      0.4). All the established models could be used in other places via the
      introduction of calibration models. In VI-VFC modeling, using VIs derived from
      different radiometric correction levels of remote sensing image could help mining
      valuable information from remote sensing image, and thus, improving the accuracy
      of VFC estimation.

PMID- 18808024
TI  - [Effects of land use type and slope position on soil physical properties in loess
      tableland area].
AB  - Soil samples under different land use types and at different slope positions in
      the Wangdonggou watershed of loess tableland area were collected to determine
      their particle composition, bulk density (pb), and saturated hydraulic
      conductivity (Ks), and the effects of land use type and slope position on the
      soil physical properties were studied in virtue of the variation coefficient and
      non-parameter tests. The results showed that the physical properties of soil
      varied in horizontal direction and vertical profile, however at the same slope
      position or under the same land use type, the pb and particle composition were
      similar. In horizontal direction, Ks varied strongly, slit content and pb varied
      weakly, and clay and sand contents varied medially. In vertical profile, soil
      particles had a continuous distribution, but pb and Ks varied greatly in 0-25 cm
      layer. With the slope degree descended, soil contained more clay and had a higher
      pb, and Ks increased. At upper and middle slopes, soil physical properties were
      similar, and thus, could be merged into one in related researches. There was a
      significant difference in soil physical properties between grassland and other
      land use types, which was mainly due to the effects of slope position, but the
      soil physical properties in farmland and orchard were similar, indicating the
      important effects of human activities.

PMID- 18808025
TI  - [Determination of 13C enrichment in soil amino acid enantiomers by gas
      chromatogram/mass spectrometry].
AB  - The transformation and renewal of amino acid enantiomers is of significance in
      indicating the turnover mechanism of soil organic matter. In this paper, a method
      of gas chromatogram/mass spectrometry combined with U-13 C-glucose incubation was
      developed to determine the 13C enrichment in soil amino acid enantiomers, which
      could effectively differentiate the original and the newly synthesized amino
      acids in soil matrix. The added U-13 C-glucose was utilized rapidly to structure
      the amino acid carbon skeleton, and the change of relative abundance of isotope
      ions could be determined by mass spectrometry. The direct incorporation of U-13 C
      glucose was estimated by the intensity increase of m/z (F + n) to F (F was parent
      fragment, and n was the carbon number in the fragment), while the total isotope
      incorporation from the added 13C could be calculated according to the abundance
      ratio increment summation from m/z (Fa + 1) through (Fa + T) (Fa was the fragment
      containing all original skeleton carbons, and T was the carbon number in the
      amino acid molecule). The 13C enrichment in the target compound was expressed as
      atom percentage excess (APE), and that of D-amino acid needed to be corrected by
      the coefficient of hydrolysis-induced racemization. The 13C enrichment reflected
      the carbon turnover velocity of individual amino acid enantiomers, and was
      powerful to investigate the dynamics of soil amino acids.

PMID- 18808026
TI  - [Landscape pattern change and its driving forces in middle and upper reaches of
      Dongting Lake watershed].
AB  - Based on GIS and RS, the landscape pattern change in the middle and upper reaches
      of Dongting Lake watershed from 1980 to 2000 was studied, with its driving forces
      analyzed. The results showed that there was a remarkable difference in the area
      change of various landscape types, with the sequence of forest land > mountain
      paddy field > open forest land. This change mainly occurred in mountainous and
      hilly areas, and had a decreasing trend from the east to the west, i. e.,
      decreased in the order of Xiangshui River valley > Zishui River valley > Yuanshui
      River valley > Lishui River valley. The patch shape was simple and regular from
      1980 to 1995, but diversified from 1995 to 2000. The main driving forces of the
      landscape pattern change were the pressure of booming farming population on
      natural ecosystem, the dependence of watershed' s development on natural
      resources, the investment to protect and improve the functions of natural
      ecosystem, and the adjustment of agricultural polices.

PMID- 18808027
TI  - [Effects of temperature on development and reproduction of Sylepta derogata
      Fabricius (Lepidoptera: Pyralidae)].
AB  - By using life table parameters, the effects of seven constant temperature regimes
      (17, 20, 23, 26, 29, 32 and 35 degrees C) on the development and reproduction of
      Sylepta derogata was investigated. The results indicated that the durations of
      egg-laying, larval, pupal, and adult stages of S. derogata shortened
      significantly when the temperature increased from 17 degrees C to 26 degrees C,
      but prolonged at 32 degrees C and 35 degrees C. The lower development threshold
      temperature of S. derogata at its all development stages was 12.08 degrees C, and
      the effective accumulative temperature was 436.2 degree-days. The survival rates
      of all immature stages were the highest at 26 degrees C, and would be decreased
      when the temperature was above or under 26 degrees C. The innate capacity to
      increase (rm), net reproductive rate (R0), and finite rate of increase (lambda)
      reached the maximum at 29, 26 and 32 degrees C, with the values being 0.1268,
      415.65 and 1.185, respectively. The mean generation time (T) shortened with
      increasing temperature, with the maximum and minimum values of 89.11 and 28.68
      days at 17 degrees C and 35 degrees C, respectively.

PMID- 18808028
TI  - [Effects of wheat-oilseed rape or wheat-garlic intercropping on the population
      dynamics of Sitobion avenae and its main natural enemies].
AB  - Sitobion avenae (Fabricius) is one of the most important pests of winter wheat in
      China. An investigation was conducted at the experimental farm of Shandong
      Agricultural University to study the effects of intercropping oilseed rape or
      garlic with winter wheat on the population dynamics of S. avenae and its main
      natural enemies. The results showed that in most cases, the population density of
      S. avenae apterae was significantly lower in wheat-oilseed rape and wheat-garlic
      intercropping fields than in wheat monoculture field. The population density of
      ladybeetle and the ratio of ladybeetle to S. avenae were higher in wheat-oilseed
      rape intercropping field. Before May 2, the population density of aphid
      parasitoids in wheat-oilseed rape intercropping field was higher than that in
      wheat-garlic intercropping field and wheat monoculture field; and after May 5,
      the mummy rate of aphid parasitoids and the ratio of aphid parasitoids to S.
      avenae in wheat-oilseed rape intercropping field were significantly higher than
      those in the other two fields. In wheat-garlic intercropping field, S. avenae
      alatae had a higher population amount, but no significant change was observed in
      the population amounts of ladybeetle and aphid parasitoids. It was concluded that
      wheat-oilseed rape or wheat-garlic intercropping could control S. avenae in wheat
      fields.

PMID- 18808029
TI  - [Effects of salinity and Na+/K+ in percolating water from saline-alkali soil on
      the growth of Litopenaeus vannamei].
AB  - In order to develop shrimp farming with the percolating water from coastal saline
      alkali soil, the effects of the salinity and Na+/K+ in this percolating water on
      the survival, growth, metabolism, and glutamic oxaloacetic transaminase (GOT),
      glutamicpyruvic transaminase (GPT) and Na+-K+-ATPase activities of Litopenaeus
      vannamei were investigated. The shrimps were cultured at the salinity 5, 10 and
      15 and at the Na+/K+ ratios of 20, 40, 50, 60, 70 and 90 for 20 days. The results
      showed that the survival rate, growth rate, and enzyme activities of the shrimps
      were the highest at salinity 15, and the shrimps had higher survival rate, growth
      rate, and enzyme activities at the Na+/K+ ratios of 40 and 50, suggesting that
      after an appropriate preparation, the percolating water from coastal saline
      alkali soil was available to culture the shrimps.

PMID- 18808030
TI  - [Acute toxicity of DDT and its effects on life table demography of Moina
      macrocopa].
AB  - The 48 h LC50 of DDT to Moina macrocopa was determined by acute toxicity test,
      and the effects of different concentrations (1, 8, 16, 24, 32 and 40 microg x L(
      1)) of DDT on the life table demography of M. macrocopa was studied by life table
      demography. The results showed that the 48 h LC50 of DDT to M. macrocopa was 324
      microg x L(-1). 1-40 microg x L(-1) of DDT had no significant effects on the life
      expectancy at birth, generation time, net reproductive rate, and gross productive
      rate of M. macrocopa (P > 0.05), but significantly affected the intrinsic rate of
      population increase (rm) (P < 0.05). The rm of M. macrocopa increased markedly at
      8, 16 and 40 microg x L(-1) of DDT, compared with the blank control, indicating
      that when the life table demography of M. macrocopa was used to monitor the
      ecological effects of sublethal concentrations of DDT, rm could be a sensitive
      indicator.

PMID- 18808031
TI  - [Kinetic characteristics of Zn uptake by Potentilla griffithii Hook. f. var.
      velutina Card].
AB  - The kinetic characteristics of Zn uptake by Potentilla griffithii Hook. f. var.
      velutina Card. were studied with hydroponic culture under different Zn supply and
      its exposure time. When the Zn supply was 10 mg x L(-1), the Zn concentration in
      shoot and root reached the peak on the 8th day, being 2.49 x 10(3) mg x kg(-1)
      and 2.21 x 10(3) mg x kg(-1), respectively; while when the supply was 100 mg x L(
      1), the Zn concentration in shoot reached the maximum (1.23 x 10(3) mg x kg(-1))
      on the 16th day, but that in root did not exhibit saturation. The Zn
      concentration in leaf and leafstalk increased with increasing Zn supply from 0 to
      160 mg x L(-1), but had no increase or even decreased when the Zn supply was
      higher than 160 mg x L(-1). The Zn concentration in root exhibited a positive
      correlation with Zn supply and its exposure time, and the kinetic curve of Zn
      uptake fitted linear-quadratic (LQ) model, i. e., fast linear uptake first and
      slow saturation uptake later, with the dividing point at about 1-2 hours'
      exposure, which could be related with the Zn adsorption on root cell wall and the
      Zn transportation across the cell membrane.

PMID- 18808032
TI  - [Effects of cadmium stress on the antioxidative system in Ganoderma lucidum
      mycelia].
AB  - The study on the effects of different concentration (0, 10, 50, 100, 200 and 400
      micromol x L(-1)) cadmium (Cd) on the antioxidative system in Ganoderma lucidum
      mycelia indicated that with increasing concentration of Cd, the fresh mass and
      the proline, total polysaccharides, and reduced polysaccharides contents of G.
      lucidum mycelia decreased, but non-protein thiol (NPT) content increased. At 400
      micromol x L(-1) of Cd, the NPT content increased dramatically, being 5.7 times
      higher than control. Within the range of test Cd concentrations, the activities
      of CAT, GR and POD increased first and decreased then, with the peak at 100
      micromol x L(-1) of Cd, while the activities of LOX and SOD increased with
      increasing Cd concentration, with the maximum at 400 micromol x L(-1) of Cd.
      Polyacrylamide gel electrophoresis analysis revealed that 100-400 micromol x L(
      1) of Cd induced two additional isozymes bands of Mn-SOD, 10-200 micromol x L(-1)
      of Cd increased the intensity of constitutive isozymes of CAT, POD, SOD and LOX,
      while 400 micromol x L(-1) of Cd decreased the intensity of isozymes of POD
      significantly.

PMID- 18808033
TI  - [Chemical forms and ecological effect of soil Mn in liver cancer's high incidence
      area in Zhu-jiang River Delta, China].
AB  - The samples of surface soil, deep soil, and vegetables were collected from the
      liver cancer's high- and low incidence areas in Zhujiang River Delta to study the
      relationships between soil Mn forms and vegetables' Mn enrichment. The results
      showed that the soil Mn in study area was mainly derived from parent materials,
      and rarely come from human activities. The average soil Mn content in liver
      cancer's high incidence area was 577.65 mg x kg(-1), being significantly lower
      than that of liver cancer's low incidence area (718.04 mg x kg(-1)) and whole
      country (710 mg x kg(-1)). The Mn forms in high incidence area were mainly of
      residual Mn and Fe-Mn oxide, and less of water soluble Mn and exchangeable Mn,
      with the sum of the latter two's distribution coefficients being not higher than
      4%. In low incidence area, the distribution pattern of soil Mn forms was similar
      to that in high incidence area, but the absolute contents of the Mn forms were
      significantly higher. Soil total Mn and soil pH had significant effects on soil
      Mn forms. There existed significant positive correlations between soil total Mn
      and the Mn forms of Fe-Mn bound, humic acid bound, carbonate bound, and residual,
      and negative correlations between soil pH and soil water soluble and organic
      bound Mn forms. Among the test five kinds of vegetables, Youmai lettuce and
      Chinese cabbage in liver cancer' s high incidence area had a significantly lower
      Mn content than in low incidence area, while the other three had less difference.
      The Mn enrichment in test vegetables was positively correlated with to the
      content of soil available Mn (sum of water soluble Mn and exchangeable Mn), but
      had no correlations with the contents of soil total Mn and other Mn forms.

PMID- 18808034
TI  - [Effects of intercropping different crops with maize on the Cd uptake by maize].
AB  - A greenhouse experiment was conducted to investigate the effects of intercropping
      7 kinds of crops on the Cd uptake by maize (Zea mays L.). The results showed that
      most intercrops had no significant effects on the growth of maize, only with
      purple haricot reduced the maize biomass by 32.2% of the control. Legume crops
      enhanced the total quantity of Cd in maize in a great magnitude, and chickpea
      worked most efficiently, which doubled the Cd quantity in maize. The 7 intercrops
      showed different capability of Cd uptake, among which, rape and amaranth absorbed
      larger amount of Cd, with a Cd level of 53.9 mg x kg(-1) and 51.0 mg x kg(-1) in
      their aboveground parts, respectively, and of 91.8 mg x kg(-1) in amaranth root
      when the soil Cd content was 3 mg x kg(-1) soil. There was an interaction between
      maize and intercrops in Cd uptake. Legumes absorbed smaller amount of Cd but
      significantly increased the Cd uptake by maize, while amaranth was in adverse.
      Rape had a higher level of Cd concentration in its shoot, but reduced the Cd in
      aboveground part of maize. It was indicated that if maize was used for
      phytoremediation of Cd-contaminated soil, a higher efficiency of Cd removal could
      be achieved by intercropping it with legumes. Rape and amaranth could be the two
      promising plants for phytoremediation because of their high Cd accumulation.

PMID- 18808035
TI  - [Soil biological evaluation on ecological remedy of damaged riparian].
AB  - In order to explore the theory and technique about the restoration of damaged
      riparian ecosystem, this paper evaluated the remedy effect of artificial spotted
      habitats that have been built for four years on the damaged riparian ecosystem
      based on soil biological principles. The results showed that in restored area,
      the quantities of various soil microbial species were significantly higher, and
      the species, quantity, and biodiversity of soil animal as well as the contents of
      soil organic matter, nitrogen, phosphorus, and potassium were all higher than
      those in un-restored area. After successful restoration, the soil conditions in
      damaged riparian were significantly improved, which resulted in an increase in
      soil biodiversity and enhanced the stability of this ecosystem. The remedy
      technique for the damaged riparian by using artificially spotted habitats not
      only consumed less cost, but also exhibited great ecological, landscape, and
      social values, providing a new model for the ecological reconstruction of damaged
      concrete riparian and the approximately natural remediation of damaged riparian.

PMID- 18808036
TI  - [Research advances in molecular ecology of ammonia oxidizing bacteria].
AB  - Ammonia oxidizing bacteria (AOB) play an important role in global nitrogen cycle.
      This paper reviewed the research advances on molecular ecology of ammonia
      oxidizing bacteria. The analysis of systematic evolution of AOB based on 16S rRNA
      reveals that the evolution of AOB is quite simple, which belongs to beta and
      gamma subgroup of Proteobacteria. This paper also introduced the main molecular
      ecological methods in the study of AOB, which included denature gradient gel
      electrophoresis (DGGE), terminal restriction fragment length polymorphism (T
      RFLP), fluorescence in situ hybridization (FISH), and real-time PCR, summarized
      the effects of ecological factors on the communities and populations of AOB, and
      prospected the research directions on molecular ecology of AOB.

PMID- 18808037
TI  - [Regulation of soil nitrification with nitrification inhibitors and related
      mechanisms].
AB  - To improve the use efficiency of fertilizer N while alleviate its pollution is
      one of the keys in ensuring the high yield and good quality of agricultural
      products and the sustainable development of agriculture and environment, for
      which, applying nitrification inhibitors to retard the course of soil
      nitrification is an efficient measure. In this review, the definition, screening
      criteria, major varieties being widely used, and action mechanisms of
      nitrification inhibitors were introduced, and the existing problems and prospects
      in related researches were discussed.

PMID- 18808038
TI  - [Toxic effect of musk ketone based on the determinations of wheat (Triticum
      aestivum) seed germination and root elongation].
AB  - Through the determinations of wheat (Triticum aestivum) seed germination and
      seedling growth, the toxic effect of emerging pollutant musk ketone was
      investigated. The results showed that 10 mg x kg(-1) of musk ketone could
      significantly inhibit the seed germination rate (P < 0. 05) and the seedling's
      root- and shoot elongation of wheat (P <0.01), and there existed a significant (P
      < 0.01) dose-effect relationship between musk ketone and root- and shoot
      elongation, suggesting that the seedling's root- and shoot elongation of wheat
      could indicate the pollution extent of musk ketone in soil. The correlation
      analysis revealed that under soil musk ketone pollution, there was a significant
      (P < 0.01) positive correlation between root- and shoot elongation, and a
      significant (P < 0.01) negative correlation between seed germination and biomass.
      Besides the solubility in water, the toxicity of organic pollutant was related to
      its chemical characters, and its action mechanisms to the target organism.

PMID- 18808039
TI  - [Effects of residual heat and chlorine in cooling water from coastal power plant
      on Calanus sinicus].
AB  - According to the practical operation of coastal power plant cooling system, a
      simulation study was conducted on the effects of residual heat and chlorine in
      the cooling water on Calanus sinicus. The results showed that the thermal
      tolerance of C. sinicus to the cooling water was decreased with increasing
      exposure duration but increased with increasing acclimation temperature. When the
      acclimation temperature was 16 degrees C-27 degrees C, the lethal temperature of
      C. sinicus under thermal shock for 15, 30 and 45 min was 29.9 degrees C-31.7
      degrees C, 29.4 degrees C-31.0 degrees C and 28.9 degrees C-30.3 degrees C, and
      that of C. sinicus continually exposed to increasing temperature for 24 and 48 h
      was 26.9 degrees C-28.5 degrees C and 26.4 degrees C-28.0 degrees C,
      respectively. When the acclimation temperature increased to a certain degree, the
      thermal tolerance of C. sinicus maintained at a stable level. The toxicity of
      residual chlorine on C. sinicus enhanced with increasing acclimation temperature,
      temperature increment, and exposure duration.

PMID- 18808040
TI  - King Solomon's take on word learning: an integrative account from the radical
      middle.

PMID- 18808041
TI  - Orthographic learning, phonological recoding, and self-teaching.

PMID- 18808042
TI  - Developmental perspectives on links between attachment and affect regulation over
      the lifespan.

PMID- 18808044
TI  - Transactional family dynamics: a new framework for conceptualizing family
      influence processes.

PMID- 18808045
TI  - The development of rational thought: a taxonomy of heuristics and biases.

PMID- 18808043
TI  - Function revisited: how infants construe functional features in their
      representation of objects.

PMID- 18808046
TI  - Lessons learned: recent advances in understanding and preventing childhood
      aggression.

PMID- 18808047
TI  - The social cognitive neuroscience of infancy: illuminating the early development
      of social brain functions.

PMID- 18808048
TI  - Children's thinking is not just about what is in the head: understanding the
      organism and environment as a unified system.

PMID- 18808049
TI  - Remote transfer of scientific-reasoning and problem-solving strategies in
      children.

PMID- 18808050
TI  - Now and then: The NMC versus Hippocrates.

PMID- 18808051
TI  - Inter-rater reliability of Glamorgan Paediatric Pressure Ulcer Risk Assessment
      Scale.
AB  - Children who are at risk of pressure ulcers need to be identified so that
      preventative measures can be taken. Most paediatric pressure ulcer risk
      assessment scales were developed using clinical experience, or by modifying adult
      scales. The Glamorgan Paediatric Pressure Ulcer Risk Assessment Scale was
      developed using detailed paediatric inpatient data. AIM: To establish whether the
      inter-rater reliability of the Glamorgan scale was adequate for use in clinical
      practice. METHOD: Fifteen qualified nurses randomly selected from staff working
      on seven paediatric wards or units in a large tertiary referral hospital have
      participated in the study to date. Nurses asked permission from the children and
      parents in their care to collect anonymous data in the risk assessment section of
      the Glamorgan scale. The nurse and the researcher independently assessed the
      child's risk. Paired risk assessments were later compared and analysed using
      SPSS. RESULTS: The total risk scores ranged from 15 to 34 (high to very high
      risk). There was 100 per cent agreement on all items except for 'inadequate
      nutrition'. CONCLUSION: These preliminary data indicate that the risk assessment
      scale is reliable. More research on the reliability and validity of this tool
      with specific paediatric patient groups should be carried out, ideally comparing
      the performance of this tool with other published paediatric pressure ulcer risk
      assessment tools.

PMID- 18808052
TI  - Improving care for children with cerebral palsy.
AB  - A report about the health care of people with learning disability published by a
      UK charity concluded that this group was discriminated against and that
      healthcare professionals had a poor understanding of their needs. A case report
      of a young person with cerebral palsy is used here to demonstrate good practice
      in the care of children with learning disabilities. The careful development over
      time of individualised solutions makes a difference to the quality of life for
      children and families. Improved understanding through education as well as
      collaborative working and family participation will help ensure that children and
      young people receive the range of services they require.

PMID- 18808053
TI  - Nutritional status assessment.

PMID- 18808054
TI  - Skills assessment using video analysis in a simulated environment: an evaluation.
AB  - Limited opportunities for the acquisition and assessment of clinical skills by
      children's nursing students has resulted in a growing use of clinical
      laboratories. Video recording and analysis have been used in these simulated
      clinical environments as a means of assessing students' skills. AIM: To explore
      student perceptions and support needs before, during and after video assessment
      in the simulated environment. METHOD: Students who were studying to be children's
      nurses and were in the second year of a three-year degree programme at one
      college were invited to participate. Data were gathered using self-completion
      questionnaires before (n = 29) and after (n = 24) the assessment experience.
      FINDINGS: Positive views of video analysis and assessment after the experience
      were similar to those identified before, although there was an increase in the
      number of comments relating to 'receiving visual feedback as well verbal'. The
      percentage of students who expressed concern before the experience decreased from
      79 per cent to 58 per cent. While some concerns such as 'nerves' and 'performance
      being affected by filming' remained, many of the other pre-experience factors
      such as 'being judged by others', 'making mistakes', 'feeling foolish or
      embarrassed' and 'worries about personal appearance' had disappeared. All
      students rated video analysis as a useful and informative method of assessment
      and most preferred to receive assessment feedback in small groups. A few students
      mentioned concerns related to consistency among assessors and supervisors.
      CONCLUSION: This evaluation showed that students regard the use of video cameras
      in the clinical skills laboratory as a useful tool for assessing competency.
      Fewer students expressed concerns about this approach after they had experienced
      it and even those who had concerns recognised the benefits. These findings
      provided valuable insights into the students' experiences which have led to
      improved approaches to the use of this method.

PMID- 18808055
TI  - Drug administration via nasogastric tube.
AB  - In 2005, the National Patient Safety Agency (NPSA) highlighted concerns about the
      management of nasogastric tubes following reports of unnecessary deaths because
      of misplaced feeding tubes in infants, children and adults. During 2006, I
      investigated the management of nasogastric tubes (NGTs) in children (Clarke and
      Richardson 2007a, 2007b). This systematic review divided primary papers into
      three principal themes: enteral feeding via the NGT; confirmation of NGT position
      and associated incidence of tube placement error; and hydration via the NGT for
      acute gastroenteritis in children. Findings of the review are summarised here in
      relation to using the nasogastric tube to administer medication to children with
      the aim of informing practice and improving safety.

PMID- 18808056
TI  - Factors affecting transition of young people with diabetes.
AB  - Lack of pre-planned, supported transitional care for adolescents that is
      undertaken at an appropriate time and involves parents can result in many young
      people 'dropping out' of adult diabetes clinics. This may affect the young
      person's health, increasing the risk of clinical and psychiatric complications.
      Although standards and guidelines exist for transitional care arrangements and
      age-appropriate facilities, the evidence shows that these are not generally
      available across the UK. Factors that affect successful transition identified
      from research are reviewed in this article and an example provided of local
      services developed from this evidence base. Transitional care issues are generic,
      not condition specific. The evidence and guidance should be implemented for all
      young people with ongoing needs, including the simple procedure of contacting all
      those who have missed an appointment.

PMID- 18808057
TI  - Shared education for professionals in child care.
AB  - A shared foundation year at the start of educational pathways for professionals
      and others who will be working with children has two main objectives: acquisition
      of knowledge and skills common to the different disciplines and development of
      flexible practitioners who understand the many roles in child care and can adapt
      as new roles emerge. A Foundation Degree in Children and Families developed at
      Canterbury Christ Church University was designed to provide a knowledge and
      skills base suitable for any worker in this field. Clear definition by regulatory
      bodies such as the Nursing and Midwifery Council of roles that exist and new
      roles that emerge are needed to help ensure clarity for progression through the
      available educational pathways. The future education of children's nurses can,
      and should, be undertaken in joint programmes with other childcare workers.

PMID- 18808058
TI  - Listening to parents and carers of children with disabilities.

PMID- 18808059
TI  - Challenges for the genetic screening in dysferlin deficiency--report of an
      instructive case and review of the literature.
AB  - The homozygous or compound heterozygous mutation of the alleles of DYSF gene
      causes dysferlinopathy resulting in limb girdle muscular dystrophy Type 2B (LGMD
      2B) or Miyoshi myopathy. However, patients with only 1 (heterozygous) mutation on
      1 allele are increasingly recognized. Based on the Leiden database (www.dmd.nl)
      among 257 different mutations resulting in dysferlin-deficient muscular
      dystrophy, pathogenic mutations were detected only on 1 allele in 45 cases, while
      the exons of the other allele did not show any pathological alterations. The
      relatively high number of these so-called heterozygous cases raises the question
      if present routine molecular techniques are sufficient alone for confirming the
      diagnosis of dysferlin deficiency. In fact, the heterogenous genetic background
      of the disease makes it impossible to make the correct diagnosis without Western
      blot of the muscle dysferlin. This paper presents the clinical, myopathological
      and molecular genetic results of a 30-year-old male with dysferlinopathy as an
      instructive case. The cDNA sequencing of the dysferlin gene revealed a single
      C5302T heterozygous mutation resulting in Arg1768Trp exchange. The paper
      highlights the importance of the protein analysis in the diagnosis of dysferlin
      deficiency, discusses the difficulties of the complete genomic analysis of the
      dysferlin gene alterations and the possible etiopathogenetic role of the
      noncoding DNA sequence of the dysferlin gene in dysferlin deficiencies.

PMID- 18808060
TI  - Krabbe's disease in two West Highland White terriers.
AB  - Two 3-month-old male West Highland White terriers were referred for progressive
      neurological disease. Histological examination of the central nervous system of
      the animals euthanized at the owner' request, revealed diffuse, bilateral and
      symmetrical white matter lesion consisting of varying degrees of demyelination
      and axonal degeneration. Accumulation of round to ovoid large mononuclear cells
      was especially observed along the blood vessels in the white matter. These cells
      were characterized by central or eccentric nuclei and highly eosinophilic,
      granular and PAS-positive cytoplasm. Stored material was stained with toluidine
      blue both at pH 4 and pH 11 and exhibited a strong PAC and no PALK activities.
      Staining for lectins revealed a positivity using Ricinus communis agglutinin-I,
      Ricinus communis agglutin-II, Triticum vulgaris and Concavalin A. Histochemical
      evaluation of intracellular material was performed on the kidney and on the
      liver, too. Ultrastructural investigations allowed to observe the cytoplasmic
      contents of globoid cells that is an admixture of degraded myelin membranes and
      different kinds of tubular aggregates. To verify if the two dogs bore the
      mutation at position 473, a method involving PCR amplification of genomic DNA
      followed by restriction-digestion was used. The diagnosis of Krabbe's disease was
      performed based on the clinical evaluation, morphological, histochemical and
      ultrastructural features.

PMID- 18808061
TI  - Neuropathology of chronic GM2 gangliosidosis due to hexosaminidase A deficiency.
AB  - Autopsy studies of late-onset GM2 gangliosidosis are sparse and only one adult
      case is on record. The case of partial Hex A deficiency presented here started in
      childhood as spinal muscular atrophy which progressed slowly over 4 decades.
      Cognitive function remained intact throughout the entire course, but during the
      last few years of life allodynia supervened. The patient died at 44 years of age.
      In good correlation with clinical observations the autopsy findings showed the
      most severe accumulation of lipid and consequent regressive change in the
      anterior horns of the spinal cord. Extensive but less severe storage was found in
      other spinal cord neurons, brain stem and selected basal ganglia. Cerebral cortex
      was virtually spared by storage but was the site of excessive formation of
      lipofuscin which was also present in many other neurons in the CNS. Marked
      storage and ganglionic loss was also found in the dorsal root ganglia, and the
      fasciculus gracilis was severely depleted of myelinated fibers. Electron
      microscopy showed accumulated gangliosides almost exclusively in the form of
      single and coalescing zebra bodies. In conclusion, the pathology in this case of
      chronic GM2 gangliosidosis, though in part conforming with previous observations,
      differed in several aspects. First, the cerebral cortex was--with only a few
      exceptions--free of ganglioside storage. Also spared was the cerebellum. In
      addition, homogeneous accumulation of zebra bodies contrasted with heterogeneity
      of neuronal inclusions found in other chronic cases. Finally, the involvement of
      sensory neurons was prominent and potentially related to allodynia. Molecular
      study of HEXA gene in this patient showed an TATC1278/? genotype.

PMID- 18808062
TI  - Anti-DARPP32 antibody-immunopositive inclusions in the brain of patients with
      multiple system atrophy.
AB  - MSA is a neurodegenerative disease and GCIs are specific pathological hallmarks
      in the brain of MSA patients. Recently, Cdk5 immunopositive GCIs were reported,
      but the function of Cdk5 in the adult human brain is not clear. Cdk5 has several
      substrates such as neurofilament and tau proteins. Among these substrates, tau
      and MAP 1B are immunopositive in GCIs. DARPP32 has been identified as a target
      for dopamine and PKA in the striatum. DARPP32 has multiple phosphorylation sites,
      and Cdk5 can phosphorylate DARPP32 at Thr75. The phosphorylation ofThr75 converts
      DARPP32 into an inhibitor of PKA. DARPP32 is also one of the major substrates of
      Cdk5, and DARPP32 is widely expressed in both neurons and glial cells. In this
      study, we determined the immunohistochemical localization of DARPP32 in the
      brains of a normal control group and patients with MSA. An anti-DARPP32 antibody
      revealed immunopositive oligodendrocytes and astrocytes widely distributed in the
      brains of the normal control group and the brain of patients with MSA. Neurons in
      the caudate, globus pallidus, substantia nigra, hypothalamus, neocortex layers II
      and III, and cerebellar Purkinje cells were all immunopositive for DARPP32 in the
      normal control brains, and the immunostaining patterns were very similar to those
      observed in patients with MSA. We found that DARPP32 was immunopositive in GCIs,
      and the localization of DARPP32 and Cdk5 was very similar in GCIs. We suggest
      that Cdk5 and its substrate DARPP32 may be involved in the formation of GCIs
      through the phosphorylation of DARPP32 in the oligodendrocytes of brains with
      MSA.

PMID- 18808063
TI  - Aggressive papillary glioneuronal tumor: case report and literature review.
AB  - Papillary glioneuronal tumors (PGNT) are a rare, recently described form of mixed
      neoplasm composed of glial and neuronal components. PGNT usually occur in
      children and young adults, and typically demonstrate low-grade pathology, with a
      low proliferative index of 1-3%. Here we describe a newly diagnosed case of PGNT
      with a more aggressive phenotype that required irradiation and chemotherapy. The
      patient was a 19-year-old female who developed progressive headaches and visual
      seizures. An MRI revealed a heterogeneously enhancing solid mass in the left
      temporo-occipital region, with significant surrounding edema and mass effect. The
      mass was resected under stealth guidance without complication. Postoperative MRI
      scans showed patchy enhancement and residual T2 and FLAIR abnormality. Pathology
      revealed a highly cellular neoplasm with papillary-like structures, containing
      cells with glial and neuronal differentiation. Regions of mitoses and focal
      necrosis were noted, along with a Ki-67 labeling index of 26%. The diagnosis was
      aggressive PGNT, and treatment consisted of conformal irradiation and concomitant
      temozolomide over 6 weeks. Postirradiation follow-up MRI scans demonstrated a
      reduction of residual enhancement and FLAIR abnormality. The patient continues
      standard-dose adjuvant temozolomide on a monthly basis, with further improvement
      on subsequent MRI scans and a stable neurologic exam. This patient demonstrates
      that PGNT may, in rare cases, display an aggressive clinicopathologic phenotype
      that requires a therapeutic approach more consistent with a high-grade glioma.

PMID- 18808064
TI  - Pineal parenchymal tumors--utility of immunohistochemical markers in
      prognostication.
AB  - BACKGROUND AND OBJECTIVE: The pineal parenchymal tumors are rare, comprising 15
      30% of all tumors of pineal region. Their histological classification alone has
      been found to be inadequate for prognostication. Hence, we correlated their
      immunohistochemical profile with the prognosis. METHODS: A retrospective analysis
      of 33 pineal parenchymal tumors treated from 1990-2004 was performed. The
      histological features of the tumors were reviewed and immunohistochemical
      staining for neurofilament protein (NF), MIB-1, synaptophysin and GFAP were
      performed. Results were correlated with the patients' survival. RESULTS: The
      study comprised 6 pineocytomas (PC), 17 pineoblastomas (PB) and 10 pineal
      parenchymal tumors with intermediate differentiation (PPT-ID) which included 3
      mixed PC/PB. The histological diagnosis was obtained from microsurgical
      biopsy/decompression, stereotactic or endoscopic biopsy. Adjuvant therapy was
      advised based on histology. All pineocytomas stained positive for NF. Most
      pineoblastomas (13/16) failed to show any immunoreactivity with NF. The mean MIB
      1 labeling index in pineocytomas, PPT of ID and pineoblastomas were 1.58, 16.1
      and 23.52 respectively (p < 0.001). All the tumors stained positive for
      synaptophysin, although the intensity of the staining varied. NF-positive tumors
      had a higher chance of disease-free state, irrespective of histological subgroup
      (p = 0.0036). The median disease-free survival in pineoblastomas with negative NF
      staining was 5 months, which was less than that of pineoblastomas with positive
      NF staining (32 months). CONCLUSIONS: Neurofilament immunoreactivity indicates
      better prognosis in pineal parenchymal tumors. The MIB-1 labeling index can be
      utilized as an additional tool to differentiate pineal parenchymal tumors into
      various subgroups.

PMID- 18808065
TI  - Expression of c-Myc, neurofibromatosis Type 2, somatostatin receptor 2 and erb-B2
      in human meningiomas: relation to grades or histotypes.
AB  - Meningiomas, which originate from arachnoid cells, represent one of the largest
      subgroups of intracranial tumors. They are generally benign, but can progress to
      malignancy. The aim of our study was to determine the expression of 4 genes, c
      Myc, neurofibromatosis Type 2 (NF2), somatostatin receptor isoform 2 (sst2) and
      erb-B2, that have been associated with tumorogenesis or, possibly, with
      aggressive behavior or recurrence of meningiomas. We measured levels of mRNAs
      coding for these genes by qRT-PCR in 51 cases and levels ofc-Myc protooncogene
      and sst2 protein by immunohistochemistry in 26 cases of meningiomas of various
      grades and histotypes. C-Myc mRNA and protein levels were not grade-related, but
      validated subdivision of the 36 benign meningiomas into two groups, Groups IA and
      IB, based on histological and clinical features (Ki-67-proliferative index,
      absence or presence of mitoses, rate of recurrence and incidence of perilesional
      edema). In addition to histopathological grading, c-Myc expression may be useful
      in predicting tumor recurrence in patients with low-grade meningiomas. NF2 mRNA
      levels and sst2 mRNA and receptor levels were not grade-related, but were
      histotype-related, with significantly higher levels in the meningothelial subtype
      than in the fibroblastic subtype. Erb-B2 mRNA levels were not grade- or histotype
      related. Furthermore, the high expression of sst2 in meningothelial meningioma
      suggests the possibility of a different tumorigenesis process in this meningioma
      subtype and may open perspectives for the diagnosis and therapy of this subtype
      using somatostatin as an antiproliferative agent.

PMID- 18808066
TI  - Concomitant radiochemotherapy in a patient with multiple sclerosis and
      glioblastoma.
AB  - The coincidence of multiple sclerosis (MS) and glioblastoma has been reported in
      several anecdotal reports. Little is known concerning the effects of radio-
      and/or chemotherapy on demyelinating brain lesions in MS patients. Moreover,
      there are no data concerning the effect of concomitant radiochemotherapy
      according to the STUPP protocol on the course ofMS in patients with coexisting
      glioblastoma. A 43-year-old male patient was diagnosed for relapsing-remitting MS
      in 1997. He received interferon and glatiramer acetate for immunomodulatory
      treatment and was stable until 2006 (EDSS < 1.5), when neurological deterioration
      occurred. He developed a left-sided hemiparesis, and an MRI showed right temporal
      contrast-enhancing mass lesion. A subsequent tumor resection was performed and
      histology revealed a glioblastoma. At the beginning of radiochemotherapy,
      treatment for multiple sclerosis (glatiramer acetate) was stopped. The tumor
      responded well to treatment and was clinically as well as radiologically stable
      until 9 months after diagnosis of glioblastoma. The typical radiological MS
      lesions remained unchanged. The patient died 12 months after diagnosis of
      glioblastoma due to tumor progression. This report demonstrates that concomitant
      radiochemotherapy according to the STUPP protocol, was safe in our patient with
      respect to the radiological as well as the clinical course of multiple sclerosis.

PMID- 18808067
TI  - Spinal cord compression through extraosseous extension of a vertebral low-grade
      hemangioendothelioma with histiocytoid differentiation.
AB  - Herein, we report the case of a 47-year-old man clinically presenting a slow
      progressive loss of lower extremity functions within 8 weeks followed by an acute
      neurogenic bladder dysfunction. The patient exhibited high-grade paralysis of
      both legs with reduced sensation from dermatome Th11 downwards as well as marked
      spasticity of the lower extremity. Neuroradiological examinations revealed a
      protruding spinal tumor with extraosseous-intraspinal extension. The resected
      tumor mass exhibited a highly vascularized tumor with architectural complexity
      and high cellularity finally leading to the diagnosis of a hemangioendothelioma.
      Interesting was the fact that the tumor vasculature exhibited many CD68-positive
      cells protruding into the lumen and, therefore, being part of a partially
      histiocytoid differentiation which is all the more uncommon in
      hemangioendothelioma. The time frame of 3 hours between embolization and tumor
      resection is too short to explain a monocytic intravascular reaction. Usually,
      hemangioendotheliomas arise from the soft tissue, lungs or liver, but intraspinal
      manifestations are only rarely observed. Furthermore, the clinical course with a
      progressive development of a paraparesis due to a hemangioendothelioma is very
      uncommon.

PMID- 18808068
TI  - Spontaneous middle-ear encephalocele: report of two cases and brief review.
AB  - We report two cases of middle-ear spontaneous (idiopathic) encephalocele in
      patients aged 69 and 82 years. To our knowledge the latter represents the oldest
      individual reported to have such a lesion. Microscopic examination shows a
      disorganized neuropil with reactive inflammatory changes and in one case, several
      cysts lined by simple cylindrical ciliated epithelium. Encephalocele must be
      included in the differential diagnoses of otorrhea and masses in the middle ear.

PMID- 18808069
TI  - Histological analysis of DuraGen in a human subject: case report.
AB  - OBJECT: DuraGen (Integra Neurosciences, Plainsboro, NJ, USA) is an avascular
      collagen matrix used for dural closure. Although, numerous animal models have
      been studied, histological transformation of DuraGen in humans has not been
      reported. MATERIAL AND METHOD: We analyzed a sample of scarred DuraGen used in a
      craniectomy patient at time of delayed cranioplasty. CONCLUSION: Histological
      analysis revealed evidence for both fibroblast infiltration and
      neovascularization of the DuraGen.

PMID- 18808070
TI  - Pathology of brainstem and hypothalamic lesions. Comment to Shukla et al.

PMID- 18808071
TI  - [Diabetes prevention with paella and company].

PMID- 18808072
TI  - [Ticks--due to climatic changes, much more than just Ixodes ricinus, TBE and Lyme
      disease].
AB  - Ectoparasitic arthropodes, like ticks, confer numerous pathogenic bacterial and
      viral germs upon human beings and/or animals. Since these vectors are
      poikilothermic, there is a strong dependence on environmental conditions.
      Climatic as well as microclimatic conditions play a major role. Against this
      background, it can be anticipated that climatic changes also influence the
      bionomics of ticks and of the pathogens conferred by them.

PMID- 18808073
TI  - [Antimycotic therapy of Tinea pedis and other foot mycoses].
AB  - Fungal foot infections belong to the most frequent infectious diseases in
      industrialized countries. In Germany, an estimated one third of the total adult
      population is suffering from a mycosis of the foot. In most cases, these
      infections are caused by a dermatophyte species, especially Trichophyton rubrum
      and T. mentagrophytes, and affect the toes and the areas between the toes,
      respectively, and/or the soles of the foot (Tinea pedis). In some cases, foot
      infections due to other fungi than dermatophytes (predominantly Candida spp.)
      have been described. Based on underlying symptoms and localization of the
      infection, there are three principal forms of foot mycoses. The most common type
      is the intertriginous type characterized by peeling, maceration and fissuring
      mostly affecting the lateral toe clefts. The rarer vesiculobullous form is
      characterized by vesicles and blisters often located on the soles. The squamous
      hyperkeratotic form, referred to as moccasin type in its extensive form, affects
      the soles, heels and lateral sites. If there is no extensive spread of infection,
      intertriginous and vesiculobullous forms can be generally successfully treated
      with topical antimycotics. The squamous hyperkeratotic form, however, should be
      treated by simultaneous application of topical and systemic antifungals. Because
      of the prescription discharge of a range of topical antimycotics, the advisory
      function of pharmacists is vitally important. In Germany, self-medication with
      "over the counter" antifungals is carried out using a range of different topical
      agents, in particular several azole derivatives and the allylamine terbinafine.
      The allylamine naftifine, the morpholine amorolfine and the pyridinone derivative
      ciclopiroxolamine are also applied. For systemic treatment, systemically
      applicable azole antifungals (fluconazole, itraconazole), terbinafine and
      griseofulvine are in use.

PMID- 18808074
TI  - [Role of physical activity in the prevention of osteoporosis].
AB  - In recent years, osteoporosis has become a leading cause of morbidity and
      mortality in elderly women. Research has demonstrated that the prevention of
      osteoporosis and osteoporosis-related fractures may best be achieved by
      initiating sound health behaviors early in life and continuing them throughout
      life. Evidence suggests that osteoporosis is easier to prevent than to treat. In
      fact, healthy early life practices, including the adequate consumption of most
      nutrients, calcium in particular, and regular physical activity, contribute to
      greater bone mineral mass and optimal peak bone mass. Bone is living tissue that
      responds to exercise by becoming stronger. Two types of exercises are important
      for building and maintaining bone mass and density: Weight-bearing exercises, in
      which bones and muscles work against gravity and resistance training that use
      muscular strength to improve muscle mass and strengthen bone. Exercise can also
      improve gait, balance, coordination, proprioception, reaction time, and muscle
      strength, even in very old and frail elderly people. Overall, the evidence
      strongly suggests that regular physical activity, especially started in childhood
      and adolescence, is a cheap and safe way of both improving bone strength and
      reducing the risk to fall.

PMID- 18808075
TI  - [Colloidal silver and ozonized olive oil for atopic dermatitis?].

PMID- 18808076
TI  - [Can asthma patients engage in diving sports?].

PMID- 18808077
TI  - [Unexplained right-sided heart failure following open heart surgery: mind the
      pericardium].
AB  - Three men, aged 67 years, 80 years and 53 years, respectively, developed signs
      and symptoms of progressive right-sided heart failure following open heart
      surgery. They were diagnosed with constrictive pericarditis based on
      echocardiography, cardiac magnetic resonance and cardiac catheterisation.
      Following pericardiectomy, two of the patients fully recovered, while one, the 80
      year-old man, died during convalescence. When signs and symptoms of progressive
      right-sided heart failure develop after open heart surgery, a diagnosis of
      constrictive pericarditis should be considered. Constrictive pericarditis after
      open heart surgery may be caused by inflammation of the pericardium; an old,
      fibrotic haemopericardium, which may be diffuse or loculated; pericardial
      adhesions; or a combination of these entities. Diagnosing constrictive
      pericarditis is difficult and may take a long time. However, it is important to
      recognise this disorder early before it has progressed to an advanced stage.
      Pericardiectomy is the only effective therapy. When performed too late, survival
      is significantly reduced.

PMID- 18808078
TI  - [Inhibition of platelet aggregation and angiotensin II-receptor blockade
      following TIA; the unexpected results of the Prevention Regimen For Effectively
      Avoiding Second Strokes (PROFESS) trial].
AB  - In the Prevention Regimen for Effectively Avoiding Second Strokes (PROFESS)
      trial, the combination of acetylsalicylic acid (50 mg) and extended-release
      dipyridamole (400 mg) (ASA+Dip) was compared with clopidogrel (75 mg) in patients
      with a recent transient ischaemic attack (TIA) or minor disabling stroke. In the
      same patients, the selective type I angiotensin II-receptor blocker telmisartan
      (80 mg) was compared with placebo. Both comparisons did not show any benefit or
      harm from any of the treatments evaluated. Therefore, ASA+Dip and clopidogrel
      should be considered effective in secondary stroke prevention following TIA or
      minor disabling stroke. ASA+Dip caused headache in 6% of patients. Clopidogrel
      can cause severe haematological side effects in rare cases; its use is hampered
      mainly by its high cost. Telmisartan was well tolerated in patients with a recent
      TIA or minor disabling stroke but should not be used for indications other than
      lowering blood pressure.

PMID- 18808079
TI  - [Endophenotypes in psychiatry: an interim evaluation].
AB  - Inheritance plays an undisputedly important role in the development of most
      psychiatric disorders. However, the genes involved have mostly not yet been
      identified. In all probability, not a single gene but a large number of genes are
      involved in each disorder. In psychiatry, a lot is expected from research into
      the relationship between so-called endophenotypes and genotypes because
      endophenotypes are more closely related to the genotype and are better defined
      and quantifiable than the phenotype. Endophenotypes are biological or
      neuropsychological markers which are (a) associated with the disorder in the
      population, (b) are themselves heritable, (c) are manifest in the absence of the
      disorder, (d) cosegregate with the illness in the families and (e) are more
      prevalent in relatives of people suffering from the disease than in the general
      population. To date only a few markers have been examined in sufficient detail to
      know whether they fulfil these criteria. Therefore it is still too early to
      evaluate the significance ofendophenotypes in psychiatry.

PMID- 18808080
TI  - [The practice guideline 'Consultation psychiatry' of the Dutch Psychiatric
      Association for psychiatric consultations in primary care and the hospital].
AB  - Psychiatric consultation in primary care as well as in the hospital is both
      effective and cost-effective if certain procedures are followed. With the
      professional guideline 'Consultation psychiatry', the Dutch Psychiatric
      Association aims at setting a standard for psychiatric consultations in non
      psychiatric settings. In general practice, the psychiatric consultation is
      preferably embedded in 'collaborative care', an integrated care model including
      the general practitioner and a case manager (usually a nurse), with the
      consultant psychiatrist being regularly available for clearly defined
      indications. The psychiatrist should see the patient himself or herself,
      establish a diagnosis and treatment plan, and provide the general practitioner
      and the patient with a so-called 'consultation letter', which is then discussed
      with both. In a general hospital, systematic screening of patients at risk of
      psychiatric comorbidity can be organised. Early detection of complex patients can
      further improve the effectiveness of psychiatric consultation. Follow-up contacts
      and investing in liaison contacts improve adherence to the advice provided.

PMID- 18808081
TI  - [Diagnostic image (387). A man with diminished consciousness after a
      trepanation].
AB  - An 80-year-old man presented with a tension pneumocephalus after burr-hole
      drainage of a subdural haematoma.

PMID- 18808082
TI  - [Recurrence of Clostridium difficile-associated diarrhoea prevented by the
      administration of a whey concentrate from specifically immunised cows;
      prospective study].
AB  - OBJECTIVE: To try to prevent recurrences of Clostridium difficile-associated
      diarrhoea (CDAD) by treatment with a specific neutralising secretory IgA-enriched
      whey-protein concentrate (40%) made from the milk of cows immunised with C.
      difficile and its toxins. DESIGN: Prospective, non-blinded, clinical cohort
      study. METHOD: In 2005-2006, 100 consecutive patients with CDAD received the whey
      concentrate for 2 weeks after completion of standard antibiotic therapy. For a
      period of 60 days after the start of the administration, the safety and
      preliminary efficacy of the whey concentrate were evaluated by means of a diary,
      blood determinations, active surveillance for adverse events, and the recurrence
      of CDAD. RESULTS: The whey concentrate was well tolerated and no safety issues
      were raised. Eleven out of 109 episodes (10%) were followed by a recurrence.
      After completion of the whey concentrate therapy, a positive test for faecal
      toxins or culture of C. difficile was predictive for the recurrence of CDAD
      (relative risk: 8.2 (95% CI: 1.04-64), and 4.7 (95% CI: 0.5-47), respectively). A
      positive faeces toxin during administration of the whey concentrate was also
      associated with an early recurrence of CDAD. CONCLUSION: Compared to historical
      and contemporary findings in control groups, the whey concentrate appeared to
      reduce the recurrence of CDAD by about 50%. However, the standard dose of the
      whey concentrate was probably not sufficient to fully neutralise the C. difficile
      toxins in faeces in all episodes.

PMID- 18808083
TI  - [Treatment of recurrent Clostridium difficile-associated diarrhoea with a
      suspension of donor faeces].
AB  - OBJECTIVE: To study the effect of treating recurrent Clostridium difficile
      associated diarrhoea (CDAD) with a suspension of donor faeces. DESIGN:
      Uncontrolled interventional study. METHOD: Patients that, despite adequate
      antibiotic therapy, had developed at least 2 recurrences ofCDAD, including at
      least one recurrence that had been treated with a vancomycin tapering regimen,
      were included in the study. Relatives or volunteers served as faeces donor. All
      donors were previously examined for the presence of HIV, hepatitis B- and C
      virus, and acute infection with cytomegalovirus or Epstein-Barr virus. The donor
      faeces were examined for the presence of C. difficile, Yersinia, Campylobacter,
      Shigella, Salmonella, and parasites. Before the infusion of donor faeces, the
      patients were treated for 4 days with vancomycin 500 mg q.i.d., followed by colon
      lavage. The suspension of 150 g of donor faeces dissolved in 300-400 ml of NaCl
      was infused into the jejunum via a duodenal catheter or into the caecum via
      colonoscopy. RESULTS: 7 CDAD patients were included and treated, including 2 with
      the hypervirulent C. difficile-strain PCR ribotype 027, toxinotype III. In 5
      patients, the defaecation frequency returned to normal almost immediately after
      treatment and the cultures and toxin tests for C. difficile were repeatedly
      negative. In the remaining 2 patients, the treatment was successful after a
      repeated infusion of faeces from a different donor. CONCLUSION: Treatment with
      donor faeces seems promising for patients who develop repeated recurrences
      despite adequate therapy and could be valuable in the future during (local)
      epidemics of the PCR ribotype 027 strain. A randomised nationwide study (FECAL
      trial) has been started in order to determine the efficacy of this treatment.

PMID- 18808084
TI  - [Endometrial and ovarian tumours and their association with obesity].
AB  - A 53-year-old woman was wheelchair-dependent and unable to work due to an extreme
      increase in abdominal circumference. Closer investigation revealed an ovarian
      tumour. A mucinous cystadenoma of the ovary weighing more than 20 kg was removed
      with laparotomy. A 63-year-old woman presented with postmenopausal haemorrhage.
      Morbid obesity and agoraphobia had prevented her from visiting a doctor earlier.
      She was eventually diagnosed with stage 1C grade III endometrial carcinoma, which
      was treated with surgery and vaginal brachytherapy. The incidence of
      gynaecological tumours is increased in patients with a high BMI. This association
      is stronger for endometrial carcinoma than for ovarian carcinoma. Obesity has a
      favourable influence on the histological grade of endometrial carcinoma, and is
      associated with lower-stage ovarian cancer. Surgery-related complications are
      more common in obese patients. Determining the optimal dose of adjuvant therapy
      is also problematic in obese patients.

PMID- 18808086
TI  - [Better medicines for children: European measures].

PMID- 18808087
TI  - Relaxation of (CS2)2(-) to its global minimum mediated by water molecules:
      photoelectron imaging study.
AB  - The coexistence of several isomers of (CS 2) 2 (-) is examined via photoelectron
      imaging at 355 and 266 nm. Assisted by theoretical calculations, the bands in the
      photoelectron spectra are assigned to the CS 2 (-).CS 2 ion-molecule complex ( C
      s symmetry, (2)A' electronic state) and two covalently bound dimer-anion
      structures: C 2 v ( (2)B 1) and D 2 h ( (2)B 3g). The isomer distribution depends
      sensitively on the ion source conditions, particularly the presence of water in
      the precursor gas mixture. The intensity variation of the photoelectron bands
      suggests that the presence of water enhances the formation of the global-minimum
      C 2 v ( (2)B 1) structure, particularly relative to the metastable (local
      minimum) ion-molecule complex. This trend is rationalized with two assumptions.
      The first is that the presence of H 2O at the cluster formation stage facilitates
      the nonadiabatic transitions necessary for reaching the global-minimum dimer
      anion equilibrium when starting from the CS 2 (-) + CS 2 asymptote. The second is
      that the initial clusters formed in the presence of water tend to have, on
      average, more internal energy, which is needed for overcoming the potential
      energy barriers separating the metastable equilibria from the global-minimum
      structure. As the covalent bonds are formed, excess solvent molecules are
      evaporated from the cluster, giving rise to stable (CS 2) 2 (-) dimer anions. In
      the (CS 2) n (-), n >or= 3, and (CS 2) 2 (-)(H 2O) m , m > 0, clusters, the
      population of the covalent-dimer core structures diminishes drastically due to
      more favorable solvent interactions with the monomer-anion (i.e., CS 2 (-)) core.

PMID- 18808085
TI  - [Epidemiology of Clostridium difficile PCR ribotype 027 in the Netherlands 2005
      present and the emergence of other subtypes].
AB  - Outbreaks of Clostridium difficile associated diarrhoea (CDAD) involving the
      virulent PCRribotype 027, toxinotype III were first reported in the Netherlands
      in 2005. This ribotype has now been detected in 26 of the 97 hospitals in the
      Netherlands. In 13 of the hospitals, the introduction of ribotype 027 was linked
      to increased CDAD incidence; this was found in 2 hospitals since December 2006.
      Ribotype 027 has also been detected in to nursing homes. In 2007, no evidence of
      ribotype 27 was found in 6 of the 12 hospitals in which ribotype 027 was
      confirmed in 2005-2006 and an outbreak of CDAD had occurred. The incidence of
      CDAD increased again in 2 hospitals that had previously had the epidemic well
      under control. Meanwhile, other PCR ribotypes appear to be gaining ground in the
      Netherlands, some of which have the same virulent characteristics as ribotype
      027. Notably, ribotype 078, which appears to be associated with livestock, is
      becoming increasingly common.

PMID- 18808088
TI  - Catalytic oxidation of H2 by N2O in the gas phase: O-atom transport with atomic
      metal cations.
AB  - Twenty-five atomic cations, M (+), that lie within the thermodynamic window for O
      atom transport catalysis of the oxidation of hydrogen by nitrous oxide, have been
      checked for catalytic activity at room temperature with kinetic measurements
      using an inductively-coupled plasma/selected-ion flow tube (ICP/SIFT) tandem mass
      spectrometer. Only 4 of these 25 atomic cations were seen to be catalytic: Fe
      (+), Os (+), Ir (+), and Pt (+). Two of these, Ir (+) and Pt (+), are efficient
      catalysts, while Fe (+) and Os (+) are not. Eighteen atomic cations (Cr (+), Mn
      (+), Co (+), Ni (+), Cu (+), Ge (+), Se (+), Mo (+), Ru (+), Rh (+), Sn (+), Te
      (+), Re (+), Pb (+), Bi (+), Eu (+), Tm (+), and Yb (+)) react too slowly at room
      temperature either in their oxidation with N 2O to form MO (+) or in the
      reduction of MO (+) by H 2. Many of these reactions are known to be spin
      forbidden and a few actually may lie outside the thermodynamic window. Three
      alkaline-earth metal monoxide cations, CaO (+), SrO (+), and BaO (+), were
      observed to favor MOH (+) formation in their reactions with H 2. A potential
      energy landscape is computed for the oxidation of H 2 with N 2O catalyzed by Fe
      (+)( (6)D) that vividly illustrates the operation of an ionic catalyst and
      qualitatively accounts for the relative inefficiency of this catalyst.

PMID- 18808089
TI  - Modulation of dynamics and reactivity of water in reverse micelles of mixed
      surfactants.
AB  - In this contribution, we attempt to correlate the change in water dynamics in a
      reverse micellar (RM) core caused by the modification of the interface by mixing
      an anionic surfactant, sodium bis(2-ethylhexyl) sulfosuccinate (AOT), and a
      nonionic surfactant, tetraethylene glycol monododecyl ether (Brij-30), at
      different proportions, and its consequent effect on the reactivity of water,
      measured by monitoring the solvolysis reaction of benzoyl chloride (BzCl). The
      dimension of the RM droplets at different mixing ratios of AOT and Brij-30
      (X(Brij-30)) has been measured using dynamic light scattering (DLS) technique.
      The physical properties of the RM water have been determined using Fourier
      transform infrared spectroscopy (FTIR) and compressibility studies, which show
      that with increasing X(Brij-30), the water properties tend toward that of bulk
      like water. The solvation dynamics, probed by coumarin 500 dye, gets faster with
      X(Brij-30). The rotational anisotropy studies along with a wobbling-in-cone
      analysis show that the probe experiences less restriction at higher X(Brij-30).
      The kinetics of the water-mediated solvolysis also gets faster with X(Brij-30).
      The increased rate of solvolysis has been correlated with the accelerated
      solvation dynamics, which is another consequence of surfactant headgroup-water
      interaction.

PMID- 18808090
TI  - Polymer-coated gold island films as localized plasmon transducers for gas
      sensing.
AB  - Ultrathin (typically < or = 10-nm thick) gold island films evaporated on
      transparent substrates show a prominent localized surface plasmon (SP) extinction
      in the visible-to-NIR range. Changes in the dielectric properties of the
      contacting medium influence the SP absorption band, providing a scheme for
      optical sensing based on refractive index change. In the present work, the gas
      sensing capability of gold island based localized surface plasmon resonance
      (LSPR) transducers was explored using polymeric coatings as the active interface.
      LSPR transducers were fabricated by spin-coating of polystyrene (PS) or
      polystyrene sulfonic acid, sodium salt (PSS) onto 5-nm-thick (nominal thickness)
      gold island films evaporated on silanized glass and annealed. Detailed
      characterization of the transducers was carried out using high-resolution
      scanning electron microscopy, cross-sectional transmission electron microscopy,
      and in situ atomic force microscopy under controlled atmosphere. The hydrophobic
      PS film exhibits swelling and significant thickness increase upon exposure to
      chloroform vapor and little or no change in water vapor, whereas the hydrophilic
      PSS film shows the opposite behavior when exposed to the same vapors. Polymer
      swelling upon absorption of vapors of good solvents shows a net effect of
      lowering the effective refractive index in the vicinity of the gold islands,
      manifested as a characteristic decrease of the SP band intensity and a blue shift
      of the band maximum. The response, measured for four different vapors, is fast
      (approximately 15 s) and reversible. It is shown that gold island systems coated
      with polymeric films can be applied to vapor recognition in an array
      configuration.

PMID- 18808091
TI  - Temperature dependence of phase behavior for ternary systems composed of ionic
      liquid + sucrose + water.
AB  - In this work, temperature dependence of phase behaviors for the [Bmim]BF 4 +
      sucrose + water system was investigated. It was found that interaction of
      [Bmim]BF 4 with sucrose is exothermic, and lowering temperature is favorable for
      phase separation. In addition, a "[Bmim] (+)-induced structural changes" model
      was developed and used to interpret the temperature effect, whereby the salting
      out effect was thought to be an entropy driving process through analysis of the
      structural interaction and the electrostatic interaction.

PMID- 18808092
TI  - Conjugated polyelectrolyte supported bead based assays for phospholipase A2
      activity.
AB  - A fluorescence based assay for human serum-derived phospholipase activity has
      been developed in which cationic conjugated polyelectrolytes are supported on
      silica microspheres. The polymer-coated beads are overcoated with an anionic
      phospholipid (1,2-dimyristoyl-sn-glycero-3-[phospho- rac-(1-glycerol)) (DMPG) to
      provide "lipobeads" that serve as a sensor for PLA2. The lipid serves a dual role
      as a substrate for PLA2 and an agent to attenuate quenching of the polymer
      fluorescence by the external electron transfer quencher 9,10-anthraquinone-2,6
      disulfonic acid (AQS). In this case quenching of the polymer fluorescence by AQS
      increases as the PLA2 digests the lipid. The lipid can also be used itself as a
      quencher and substrate by employing a small amount of energy transfer quencher
      substituted lipid in the DMPG. In this case the fluorescence of the polymer is
      quenched when the lipid layer is intact; as the enzyme digests the lipid, the
      fluorescence of the polymer is restored. The sensing of PLA2 activity has been
      studied both by monitoring fluorescence changes in a multiwell plate reader and
      by flow cytometry. The assay exhibits good sensitivity with EC50 values in the
      nanomolar range.

PMID- 18808093
TI  - Light scattering studies of amphiphilic drugs promethazine hydrochloride and
      imipramine hydrochloride in aqueous electrolyte solutions.
AB  - Two amphiphilic drugs, promethazine hydrochloride (PMT) and imipramine
      hydrochloride (IMP), have been studied using both static and dynamic light
      scattering techniques. Due to having rigid tricyclic hydrophobic moieties in
      their molecules, these drugs show interesting association behavior. The static
      light scattering (SLS) measurements show that the self-association commenced
      above a well-defined critical micellar concentration ( cmc), which decreases with
      increasing NaBr concentration. The Gibbs energy of micellization, DeltaG(0)M, in
      all cases, is negative. The colloidal stability of the system in terms of the
      interparticle interaction at different NaBr concentrations was studied using the
      dynamic light scattering (DLS) technique. The experimentally evaluated
      interparticle interaction parameter ( k D ) was compared with the Derjaguin
      Landau-Verwey-Overbeek (DLVO) model. Interestingly, these two drugs with similar
      molecular structure show difference in their interparticle interactions, e.g.,
      PMT showed complete agreement with the DLVO model whereas IMP showed clear
      deviation from this model at lower concentrations and agreement at higher
      concentrations of NaBr.

PMID- 18808094
TI  - Peptide folding using multiscale coarse-grained models.
AB  - The multiscale coarse-graining (MS-CG) method has been previously used to
      describe the equilibrium properties of peptides. The present study reveals that
      MS-CG models of alpha-helical polyalanine and the beta-hairpin V 5PGV 5 possess
      the capacity to efficiently refold in simulations initiated from unfolded
      configurations. The MS-CG peptides exhibit free energy landscapes that are
      funneled toward folded configurations and two-state folding behavior, consistent
      with the known characteristics of small, rapidly folding peptides. Moreover, the
      models demonstrate enhanced sampling capabilities when compared to systems with
      full atomic detail. The significance of these observations with respect to the
      theoretical basis of the MS-CG approach is discussed. The MS-CG peptides were
      used to reconstruct atomically detailed configurations in order to evaluate the
      extent to which MS-CG ensembles embody all-atom peptide free energy landscapes.
      Ensembles obtained from these reconstructed configurations display good agreement
      with the all-atom simulation data used to generate the MS-CG models and also
      corroborate the presence of features observed in the MS-CG peptide free energy
      landscapes. These findings suggest that MS-CG models may be of significant
      utility in the study of peptide folding.

PMID- 18808095
TI  - Equilibrium adsorption on a random site surface.
AB  - We examine the reversible adsorption of spherical solutes on a random site
      surface in which the adsorption sites are uniformly and randomly distributed on a
      substrate. Each site can be occupied by one solute provided that the nearest
      occupied site is at least one diameter away. The model is characterized by the
      site density and the bulk phase activity of the adsorbate. We develop a general
      statistical mechanical description of the model, and we obtain exact expressions
      for the adsorption isotherms in limiting cases of large and small activity and
      site density, particularly for the one-dimensional version of the model. We also
      propose approximate isotherms that interpolate between the exact results. These
      theories are in good agreement with numerical simulations of the model in two
      dimensions.

PMID- 18808096
TI  - Combining ligand-based pharmacophore modeling, quantitative structure-activity
      relationship analysis and in silico screening for the discovery of new potent
      hormone sensitive lipase inhibitors.
AB  - Hormone sensitive lipase (HSL) has been recently implicated in diabetes and
      obesity, prompting attempts to discover new HSL inhibitors. Toward this end, we
      explored the pharmacophoric space of HSL inhibitors using four diverse sets of
      compounds. Subsequently, genetic algorithm and multiple linear regression
      analysis were employed to select optimal combination of pharmacophoric models and
      2D physicochemical descriptors capable of yielding a self-consistent and
      predictive quantitative structure-activity relationship (QSAR) (r = 0.822, n =
      99, F = 11.1, r LOO (2) = 0.521, r PRESS (2) against 23 external test inhibitors
      = 0.522). Interestingly, two pharmacophoric models emerged in the QSAR equation
      suggesting at least two binding modes. These pharmacophores were employed to
      screen the National Cancer Institute (NCI) list of compounds and our in-house
      built database of established drugs and agrochemicals. Active hits included the
      safe herbicidal agent bifenox (IC 50 = 0.43 microM) and the nonsteroidal anti
      inflammatory naproxen (IC 50 = 1.20 microM). Our active hits undermined the
      traditional believe that HSL inhibitors should possess covalent bond-forming
      groups.

PMID- 18808097
TI  - Solution kinetics measurements suggest HIV-1 protease has two binding sites for
      darunavir and amprenavir.
AB  - Darunavir, a potent antiviral drug, showed an unusual second binding site on the
      HIV-1 protease dimer surface of the V32I drug resistant mutant and normal binding
      in the active site cavity. Kinetic analysis for wild type and mutant protease
      showed mixed-type competitive-uncompetitive inhibition for darunavir and the
      chemically related amprenavir, while saquinavir showed competitive inhibition.
      The inhibition model is consistent with the observed second binding site for
      darunavir and helps to explain its antiviral potency.

PMID- 18808099
TI  - Application of the valence bond mixing configuration diagrams to hypervalency in
      trihalide anions: a challenge to the Rundle-Pimentel model.
AB  - The X(3)(-) hypercoordinated anions (H, F, Cl, Br, I) are studied by means of the
      breathing-orbital valence bond ab initio method. The valence bond wave functions
      describe the different X(3)(-) complexes in terms of only six valence bond
      structures and yield energies relative to the two exit channels, X(2) + X(-) and
      X(2)(-) + X(*), in very good agreement with reference CCSD(T) calculations.
      Although H(3)(-) is unstable and dissociates to H(2) + H(-), all the trihalogen
      anions are stable intermediates, Br(3)(-) and I(3)(-) being more stable than
      F(3)(-) and Cl(3)(-). As a challenge to the traditional Rundle-Pimentel model,
      the different energies of the hypercoordinated species relative to the normal
      valent dissociation products X(2) + X(-) are interpreted in terms of valence bond
      configuration mixing diagrams and found to correlate with a single parameter of
      the X(2) molecule, its singlet-triplet energy gap. Examination of the six
      structure wave functions show that H(3)(-), Cl(3)(-), Br(3)(-), and I(3)(-) share
      the same bonding picture and can be mainly described in terms of the interplay of
      two Lewis structures. On the other hand, F(3)(-) is bonded in a different way and
      possesses a significant three-electron bonding character that is responsible for
      the dissociation of this complex to F(2)(-) + F(*), instead of the more stable
      products F(2) + F(-). This counterintuitive preference for the thermodynamically
      disfavored exit channel is found to be an experimental manifestation of the large
      charge-shift resonance energy that generally characterizes fluorine-containing
      bonds.

PMID- 18808100
TI  - A Gaussian-3 theoretical study of small silicon-lithium clusters: electronic
      structures and electron affinities of SinLi(-) (n = 2-8).
AB  - The molecular structures of neutral Si n Li ( n = 2-8) species and their anions
      have been studied by means of the higher level of the Gaussian-3 (G3) techniques.
      The lowest energy structures of these clusters have been reported. The ground
      state structures of neutral clusters are "attaching structures", in which the Li
      atom is bound to Si n clusters. The ground-state geometries of anions, however,
      are "substitutional structures", which is derived from Si n+1 by replacing a Si
      atom with a Li (-). The electron affinities of Si n Li and Si n have been
      presented. The theoretical electron affinities of Si n are in good agreement with
      the experiment data. The reliable electron affinities of Si n Li are predicted to
      be 1.87 eV for Si 2Li, 2.06 eV for Si 3Li, 2.01 eV for Si 4Li, 2.61 eV for Si
      5Li, 2.36 eV for Si 6Li, 2.21 eV for Si 7Li, and 3.18 eV for Si 8Li. The
      dissociation energies of Li atom from the lowest energy structures of Si n Li and
      Si atom from Si n clusters have also been estimated respectively to examine
      relative stabilities.

PMID- 18808101
TI  - Kinetics of ion-molecule reactions with 2-chloroethyl ethyl sulfide at 298 K: a
      search for CIMS schemes for mustard gas.
AB  - The rate constants and product ion branching ratios have been measured in a
      selected ion flow tube (SIFT) at 298 K for a variety of positive and negative
      ions reacting with 2-chloroethyl ethyl sulfide (2-CEES), a surrogate for mustard
      gas (HD). This series of experiments is designed to elucidate ion-molecule
      reactions that have large rate constants and produce unique product ions to guide
      the development of chemical ionization mass spectrometry (CIMS) detection methods
      for the chemical weapon agent using the surrogate instead. The negative ions
      typically used in CIMS instruments are essentially unreactive with 2-CEES, that
      is, SF 6 (-), SF 4 (-), CF 3O (-), and CO 3 (-). A few negative ions such as NO 2
      (-) and NO 3 (-) undergo three-body association to give a unique product ion, but
      the bimolecular rate constants are small in the SIFT. Positive ions typically
      react at the collisional limit, primarily by charge and proton transfer, some of
      which is dissociative. For ions with high proton binding energies, association
      with 2-CEES has also been observed. Many of these reactions produced ions with
      the 2-CEES intact, including the parent cation, the protonated cation, and
      clusters. G3(MP2) calculations of the thermochemical properties for 2-CEES and
      mustard have been performed, along with calculations of the structures for the
      observed product cations. Reacting a series of protonated neutral molecules with
      2-CEES brackets the proton affinity (PA) to between 812 ((CH 3) 2CO) and 854 (NH
      3) kJ mol (-1). G3(MP2) calculations give a PA for 2-CEES of 823 kJ mol (-1) and
      a PA for mustard of 796 kJ mol (-1), indicating that the present results for 2
      CEES should be directly transferable to mustard to design a CIMS detection
      scheme.

PMID- 18808102
TI  - Oxidation of cyclohexane by a high-valent iron bispidine complex: a combined
      experimental and computational mechanistic study.
AB  - Experimental data suggest that there are various competing pathways for the
      catalytic and stoichiometric oxygenation of cyclohexane, assisted by iron
      bispidine complexes and using various oxidants (H(2)O(2), O(2), PhIO). Density
      functional theory calculations indicate that both Fe(IV)=O and Fe(V)=O species
      are accessible and efficiently transfer their oxygen atoms to cyclohexane. The
      reactivities of the two isomers each and the two possible spin states for the
      Fe(IV)=O and Fe(V)=O species are sufficiently different to allow an
      interpretation of the experimental data.

PMID- 18808103
TI  - Statistical rate theory and kinetic energy-resolved ion chemistry: theory and
      applications.
AB  - Ion chemistry, first discovered 100 years ago, has profitably been coupled with
      statistical rate theories, developed about 80 years ago and refined since. In
      this overview, the application of statistical rate theory to the analysis of
      kinetic-energy-dependent collision-induced dissociation (CID) reactions is
      reviewed. This procedure accounts for and quantifies the kinetic shifts that are
      observed as systems increase in size. The statistical approach developed allows
      straightforward extension to systems undergoing competitive or sequential
      dissociations. Such methods can also be applied to the reverse of the CID
      process, association reactions, as well as to quantitative analysis of ligand
      exchange processes. Examples of each of these types of reactions are provided and
      the literature surveyed for successful applications of this statistical approach
      to provide quantitative thermochemical information. Such applications include
      metal-ligand complexes, metal clusters, proton-bound complexes, organic
      intermediates, biological systems, saturated organometallic complexes, and
      hydrated and solvated species.

PMID- 18808104
TI  - Extrapolating to the one-electron basis set limit in polarizability calculations.
AB  - We report calculations of polarizabilities using total energies extrapolated to
      the complete basis set limit. A dual-level scheme has been employed, with the
      complete basis set limit of the correlation energy determined by the recently
      reported uniform singlet- and triplet-pair extrapolation method. The finite field
      approach has been employed, with tensors and averaged polarizabilities for the
      ground electronic states of H 2, N 2, CO, and H 2O reported and compared with
      available experimental data in the literature. Exploratory results are also
      presented for C 6H 4NO 2NH 2.

PMID- 18808105
TI  - Identification of non-nucleoside DNA synthesis inhibitors of vaccinia virus by
      high-throughput screening.
AB  - Variola virus, the causative agent of smallpox, is a potential bioweapon. The
      development of new antiviral compounds for smallpox prophylaxis and treatment is
      critical, especially because the virus can acquire resistance to the drugs that
      are currently available. We have identified novel small chemical inhibitors that
      target DNA synthesis of vaccinia, the prototypical poxvirus. Robotic high
      throughput screening of 49663 compounds and follow-up studies identified very
      potent inhibitors of vaccinia DNA synthesis, with IC 50 values as low as 0.5
      microM. Cell-based assays showed that 16 inhibitors effectively blocked vaccinia
      infection with minimal cytotoxicity. Three inhibitors had selectivity indexes
      that approximate that of cidofovir. These new non-nucleoside inhibitors are
      expected to interfere with components of the vaccinia DNA synthesis apparatus
      that are distinct from cidofovir. On the basis of the high sequence similarity
      between the proteins of vaccinia and variola viruses, these new inhibitors are
      anticipated to be equally effective against smallpox.

PMID- 18808106
TI  - Volatile anesthetic binding to proteins is influenced by solvent and aliphatic
      residues.
AB  - The main objective of this work was to characterize VA binding sites in multiple
      anesthetic target proteins. A computational algorithm was used to quantify the
      solvent exclusion and aliphatic character of amphiphilic pockets in the
      structures of VA binding proteins. VA binding sites in the protein structures
      were defined as the pockets with solvent exclusion and aliphatic character that
      exceeded minimum values observed in the VA binding sites of serum albumin,
      firefly luciferase, and apoferritin. We found that the structures of VA binding
      proteins are enriched in these pockets and that the predicted binding sites were
      consistent with experimental determined binding locations in several proteins.
      Autodock3 was used to dock the simulated molecules of 1,1,1,2,2
      pentafluoroethane, difluoromethyl 1,1,1,2-tetrafluoroethyl ether, and sevoflurane
      and the isomers of halothane and isoflurane into these potential binding sites.
      We found that the binding of the various VA molecules to the amphiphilic pockets
      is driven primarily by VDW interactions and to a lesser extent by weak hydrogen
      bonding and electrostatic interactions. In addition, the trend in Delta G binding
      values follows the Meyer-Overton rule. These results suggest that VA potencies
      are related to the VDW interactions between the VA ligand and protein target. It
      is likely that VA bind to sites with a high degree of solvent exclusion and
      aliphatic character because aliphatic residues provide favorable VDW contacts and
      weak hydrogen bond donors. Water molecules occupying these sites maintain pocket
      integrity, associate with the VA ligand, and diminish the unfavorable solvation
      enthalpy of the VA. Water molecules displaced into the bulk by the VA ligand may
      provide an additional favorable enthalpic contribution to VA binding. Anesthesia
      is a component of many health related procedures, the outcomes of which could be
      improved with a better understanding of the molecular targets and mechanisms of
      anesthetic action.

PMID- 18808107
TI  - Synthesis and characterization of the trihalophosphine compounds of ruthenium
      [RuX2(eta(6)-cymene)(PY3)] (X = Cl, Br, Y = F, Cl, Br) and the related PF2(NMe2)
      and P(NMe2)3 compounds; multinuclear NMR spectroscopy and the X-ray single
      crystal structures of [RuBr2(eta(6)-cymene)(PF3)], [RuBr2(eta(6)
      cymene)(PF2{NMe2})], and [RuI2(eta(6)-cymene)(P{NMe2}3)].
AB  - Treatment of the dimers [RuX2(eta(6)-cymene)]2 with PF3 in hot heptane produces
      the compounds [RuX2(eta(6)-cymene)(PF3)] (X = Cl, Br, I) in good yield.
      Difluoro(dimethylamino)phosphine and tris(dimethylamino)phosphine react similarly
      to produce the compounds [RuX2(eta(6)-cymene)(PF2{NMe2})] and [RuX2(eta(6)
      cymene)(P{NMe2}3)]. Reaction of the dimers [RuX2(eta(6)-cymene)]2 with PCl3 and
      PBr3 proceeded with the production of mononuclear products which had undergone
      halogen exchange at ruthenium in some cases. (1)H, (13)C, (31)P, and (19)F NMR
      spectra have been obtained where appropriate together with ((1)H-(1)H)
      correlation spectroscopy (COSY) and ((13)C-(1)H)-HETCORR spectra of selected
      compounds. The variation of (1)J((31)P-(19)F) with the nature of the auxiliary
      ligand (X) in the PF3 and PF2(NMe2) complexes has been examined both
      experimentally and computationally using a natural localized molecular orbital
      natural bond order approach. The single crystal X-ray structure of [RuBr2(eta(6)
      cymene)(PF3)] has been determined at 223 K and those of [RuBr2(eta(6)
      cymene)(PF2{NMe2})] and [RuI2(eta(6)-cymene)(P{NMe2}3)] at 294 K.

PMID- 18808109
TI  - Organocadmium aminoalcoholates: synthesis, structure, and materials chemistry.
AB  - The novel methylcadmium aminoalkoxides MeCd(dmae) (Hdmae = dimethylaminoethanol),
      MeCd(bdmap) [Hbdmap = 1,3- bis-(dimethylamino)-propan-2-ol], and MeCd(tdmap)
      [tdmap = 1,3- bis(dimethylamino)-2-(dimethylaminomethyl)-propan-2-ol] have been
      synthesized and structurally characterized. MeCd(dmae) (1) forms a tetrameric
      heterocubane with a Cd4O4 core, while MeCd(bdmap) (2) is trimeric and MeCd(tdmap)
      (3) is a dimer. Only in the case of MeCd(dmae) are all the ligand donors fully
      utilized. In solution, MeCd(tdmap) undergoes a Schlenk equilibrium, with Me2Cd
      and Cd(tdmap)2 evident at 218 K. The structure and solution-state chemistry of
      Cd(tdmap)2 (5) have been independently studied and, in the solid-state, found to
      exist as a dimer whose coordination number at cadmium (CN = 6) is greater than in
      the organocadmium complexes (CN = 4, 5). MeCd(tdmap) has been used as a single
      source precursor for CdO films by LPCVD with a glass substrate temperature of
      only 140 degrees C. Evidence is also presented for the formation of a
      heterometallic precursor, [(MeZn)(MeCd)(tdmap)2] (6), which has been used to
      deposit films of CdO mixed with ZnO by LPCVD at 140 degrees C. The structure of
      Me4Cd4(tdmap)2Cl2 (4), obtained serendipitously, is also included. Crystal data:
      1, C20H52Cd4N4O4, FW 862.26, triclinic, P1, a = 11.47560(10), b = 13.55400(10), c
      = 21.5966(2) A, alpha = 99.7869(4), beta = 90.7476(4), gamma = 98.7823(4)
      degrees, V = 3268.82(5) A(3), Z = 4; 2, C27H67Cd3N6O3, FW 861.07, triclinic, P1,
      a = 11.4148(2), b =13.1886(2), c = 14.3139(3) A, alpha = 102.1962(10), beta =
      108.3064(10), gamma = 100.8446(10) degrees, V = 1923.09(6) A(3), Z = 4; 3,
      C22H54Cd2N6O2, FW 659.51, monoclinic, P2(1)/n, a = 10.2912(1), b = 13.46930(1), c
      = 11.79130(1) A, beta = 112.8051(1) degrees, V = 1506.59(2) A(3), Z = 2; 4,
      C24H60Cd4Cl2N6O2, FW 985.28, monoclinic, P2(1)/c, a = 10.89780(10), b =
      20.3529(2), c = 16.5317(2) A, beta = 94.8550(10) degrees, V = 3653.61(7) A(3), Z
      = 4; 5, C40H96Cd2N12O4, FW 1034.09, orthorhombic, P2(1)cn, a = 12.33290(10), b =
      14.25060(10), c = 29.9003(2) A, V = 5255.01(7) A(3), Z = 4.

PMID- 18808108
TI  - The metal loading ability of beta-amyloid N-terminus: a combined potentiometric
      and spectroscopic study of copper(II) complexes with beta-amyloid(1-16), its
      short or mutated peptide fragments, and its polyethylene glycol (PEG)-ylated
      analogue.
AB  - Alzheimer's disease (AD) is becoming a rapidly growing health problem, as it is
      one of the main causes of dementia in the elderly. Interestingly, copper(II)
      (together with zinc and iron) ions are accumulated in amyloid deposits,
      suggesting that metal binding to Abeta could be involved in AD pathogenesis. In
      Abeta, the metal binding is believed to occur within the N-terminal region
      encompassing the amino acid residues 1-16. In this work, potentiometric,
      spectroscopic (UV-vis, circular dichroism, and electron paramagnetic resonance),
      and electrospray ionization mass spectrometry (ESI-MS) approaches were used to
      investigate the copper(II) coordination features of a new polyethylene glycol
      (PEG)-conjugated Abeta peptide fragment encompassing the 1-16 amino acid residues
      of the N-terminal region (Abeta(1-16)PEG). The high water solubility of the
      resulting metal complexes allowed us to obtain a complete complex speciation at
      different metal-to-ligand ratios ranging from 1:1 to 4:1. Potentiometric and ESI
      MS data indicate that Abeta(1-16)PEG is able to bind up to four copper(II) ions.
      Furthermore, in order to establish the coordination environment at each metal
      binding site, a series of shorter peptide fragments of Abeta, namely, Abeta(1-4),
      Abeta(1-6), AcAbeta(1-6), and AcAbeta(8-16)Y10A, were synthesized, each
      encompassing a potential copper(II) binding site. The complexation properties of
      these shorter peptides were also comparatively investigated by using the same
      experimental approach.

PMID- 18808110
TI  - Trinuclear Mo3S7 clusters coordinated to dithiolate or diselenolate ligands and
      their use in the preparation of magnetic single component molecular conductors.
AB  - A general route for the preparation of a series of dianionic Mo3S7 cluster
      complexes bearing dithiolate or diselenolate ligands, namely, [Mo3S7L3](2-)
      (where L = tfd (bis(trifluoromethyl)-1,2-dithiolate) (4(2-)), bdt (1,2
      benzenedithiolate) (5(2-)), dmid (1,3-dithia-2-one-4,5-dithiolate) (6(2-)), and
      dsit (1,3-dithia-2-thione-4,5-diselenolate) (7(2-))) is reported by direct
      reaction of [Mo3S7Br6](2-) and (n-Bu)2Sn(dithiolate). The redox properties,
      molecular structure, and electronic structure (BP86/VTZP) of the 4(2-) to 7(2-)
      clusters have also been investigated. The HOMO orbital in all complexes is
      delocalized over the ligand and the Mo3S7 cluster core. Ligand contributions to
      the HOMO range from 61.67% for 4(2-) to 82.07% for 7(2-), which would allow fine
      tuning of the electronic and magnetic properties. These dianionic clusters
      present small energy gaps between the HOMO and HOMO-1 orbitals (0.277-0.104 eV).
      Complexes 6(2-) and 7(2-) are oxidized to the neutral state to afford
      microcrystalline or amorphous fine powders that exhibit semiconducting behavior
      and present antiferromagnetic exchange interactions. These compounds are new
      examples of the still rare single-component conductors based on cluster magnetic
      units.

PMID- 18808111
TI  - A heterometallic, heterovalent Cu(I)/Sn(II/IV)/S cluster with an unprecedented
      Cu4Sn core and stannacyclopentane units.
AB  - [(Ph3PCu(I))6{(CH2)4Sn(IV)S2}6Cu(I)4Sn(II)], a walnut-type, heterometallic,
      heterovalent cluster, as confirmed by density functional theory calculations, was
      obtained under reductive solvothermal conditions and features an unprecedented
      metalloid core within a metal sulfide shell and an organic surface.

PMID- 18808112
TI  - Solid- and solution phase transformations in novel hybrid iodoplumbate
      derivatives templated by solvated yttrium complexes.
AB  - Solvated yttrium iodide precursors [Y(L)8]I3 [L = dimethylformamide (DMF) or
      dimethylsulfoxide (DMSO)], prepared in situ by stirring YI3(Pr(i)OH)4 in
      DMF/DMSO, react with 3 equiv of PbI2 in the presence of NH4I to give novel hybrid
      derivatives based on either a one-dimensional (1D) straight chain,
      [Y(DMF)8][Pb3(mu-I)9](1infinity) x DMF (1), or discrete pentanuclear
      iodoplumbates, [Y(DMSO)8]2[(DMSO)2Pb5(mu3-I)2(mu-I)8I6] (2a). The complex 2a and
      a closely related [Y(DMSO)8][Y(DMSO)7(DMF)][(DMSO)2Pb5(mu3-I)2(mu-I)8I6] (2b)
      were obtained in good yield by solution phase transformation of 1 in DMSO under
      slight different conditions. Derivatives 1 and 2 also undergo unique solid-state
      transformation in a confined environment of paratone to give 1D polymers based on
      zigzag iodoplumbate chains; crystals of 1 transform into [Y(DMF)6(H2O)2][Pb3(mu3
      I)(mu-I)7I](1infinity) (3) via an exchange reaction, whereas those of 2a and 2b
      are converted into [Y(DMSO)7][Pb3(mu3-I)(mu-I)7I](1infinity) (4) via a
      decomposition pathway. The trifurcate H-bonding between water ligands on yttrium
      cation and iodide of the iodoplumbate anion plays a pivotal role in transforming
      the straight 1D polymeric Pb-I chain of 1 into a zigzag chain in 3. The
      thermogravimetry-differential thermal analysis studies indicate that complexes
      with DMF ligands are thermally more stable than those with DMSO ones, the mixed
      DMF-H2O ligand complex 3 being the most stable one because of the presence of
      strong H-bonding. Diffuse-reflectance UV-visible spectral analyses of 1-4 show an
      optical band gap in the 1.86-2.54 eV range, indicating these derivatives as
      potential semiconductors. In contrast to non-emissive 3 and 4, derivatives 1, 2a,
      and 2b show remarkable luminescent emission with peak maxima at 703 nm, assigned
      as an iodine 5p-lead 6s to lead 6p charge transfer (XM-M-CT).

PMID- 18808113
TI  - High and low spin mononuclear and dinuclear iron(II) complexes of 4-amino and 4
      pyrrolyl-3,5-di(2-pyridyl)-4H-1,2,4-triazoles.
AB  - The first dinuclear iron(II) complexes of any 4-substituted 3,5-di(2-pyridyl)-4H
      1,2,4-triazole ligands, [Fe(II)2(adpt)2(H2O)1.5(CH3CN)2.5](BF4)4 and
      [Fe(II)2(pldpt)2(H2O)2(CH3CN)2](BF4)4, are presented [where adpt is 4-amino-3,5
      di(2-pyridyl)-4H-1,2,4-triazole and pldpt is 4-pyrrolyl-3,5-di(2-pyridyl)-4H
      1,2,4-triazole]. Both dinuclear complexes feature doubly triazole bridged
      iron(II) centers that are found to be [high spin-high spin] at all temperatures,
      4-300 K, and to exhibit weak antiferromagnetic coupling. In the analogous
      monometallic complexes, [Fe(II)(Rdpt)2(X)2](n+), the spin state of the iron(II)
      center was controlled by appropriate selection of the axial ligands X.
      Specifically, both of the chloride complexes, [Fe(II)(adpt)2(Cl)2] x 2 MeOH and
      [Fe(II)(pldpt)2(Cl)2] x 2 MeOH x H2O, were found to be high spin whereas the
      pyridine adduct [Fe(II)(adpt)2(py)2](BF4)2 was low spin. Attempts to prepare
      [Fe(II)(pldpt)2(py)2](BF4)2 and the dinuclear analogues
      [Fe(II)2(Rdpt)2(py)4](BF4)4 failed, illustrating the significant challenges faced
      in attempts to develop control over the nature of the product obtained from
      reactions of iron(II) and these bis-bidentate ligands.

PMID- 18808114
TI  - Near-quantitative internal quantum efficiency in a light-emitting electrochemical
      cell.
AB  - A green-light-emitting iridium(III) complex was prepared that has a
      photoluminescence quantum yield in a thin-film configuration of almost unity.
      When used in a simple solid-state single-layer light-emitting electrochemical
      cell, it yielded an external quantum efficiency of nearly 15% and a power
      efficiency of 38 Lm/W. We argue that these high external efficiencies are only
      possible if near-quantitative internal electron-to-photon conversion occurs. This
      shows that the limiting factor for the efficiency of these devices is the
      photoluminescence quantum yield in a solid film configuration. The observed
      efficiencies show the prospect of these simple electroluminescent devices for
      lighting and signage applications.

PMID- 18808115
TI  - Synthesis and reactivity of Ir(I) and Ir(III) complexes with MeNH2, Me2C=NR (R =
      H, Me), C,N-C6H4{C(Me)=N(Me)}-2, and N,N'-RN=C(Me)CH2C(Me2)NHR (R = H, Me)
      ligands.
AB  - Complexes [Ir(Cp*)Cl(n)(NH2Me)(3-n)]X(m) (n = 2, m = 0 (1), n = 1, m = 1, X = Cl
      (2a), n = 0, m = 2, X = OTf (3)) are obtained by reacting [Ir(Cp*)Cl(mu-Cl)]2
      with MeNH2 (1:2 or 1:8) or with [Ag(NH2Me)2]OTf (1:4), respectively. Complex 2b
      (n = 1, m = 1, X = ClO 4) is obtained from 2a and NaClO4 x H2O. The reaction of 3
      with MeC(O)Ph at 80 degrees C gives [Ir(Cp*){C,N-C6H4{C(Me)=N(Me)}-2}(NH2Me)]OTf
      (4), which in turn reacts with RNC to give [Ir(Cp*){C,N-C6H4{C(Me)=N(Me)}
      2}(CNR)]OTf (R = (t)Bu (5), Xy (6)). [Ir(mu-Cl)(COD)]2 reacts with
      [Ag{N(R)=CMe2}2]X (1:2) to give [Ir{N(R)=CMe2}2(COD)]X (R = H, X = ClO4 (7); R =
      Me, X = OTf (8)). Complexes [Ir(CO)2(NH=CMe2)2]ClO4 (9) and
      [IrCl{N(R)=CMe2}(COD)] (R = H (10), Me (11)) are obtained from the appropriate
      [Ir{N(R)=CMe2}2(COD)]X and CO or Me4NCl, respectively. [Ir(Cp*)Cl(mu-Cl)]2 reacts
      with [Au(NH=CMe2)(PPh3)]ClO4 (1:2) to give [Ir(Cp*)(mu-Cl)(NH=CMe2)]2(ClO4)2 (12)
      which in turn reacts with PPh 3 or Me4NCl (1:2) to give
      [Ir(Cp*)Cl(NH=CMe2)(PPh3)]ClO4 (13) or [Ir(Cp*)Cl2(NH=CMe2)] (14), respectively.
      Complex 14 hydrolyzes in a CH2Cl2/Et2O solution to give [Ir(Cp*)Cl2(NH3)] (15).
      The reaction of [Ir(Cp*)Cl(mu-Cl)]2 with [Ag(NH=CMe2)2]ClO4 (1:4) gives
      [Ir(Cp*)(NH=CMe2)3](ClO4)2 (16a), which reacts with PPNCl (PPN = Ph3=P=N=PPh3)
      under different reaction conditions to give [Ir(Cp*)(NH=CMe2)3]XY (X = Cl, Y =
      ClO4 (16b); X = Y = Cl (16c)). Equimolar amounts of 14 and 16a react to give
      [Ir(Cp*)Cl(NH=CMe2)2]ClO4 (17), which in turn reacts with PPNCl to give
      [Ir(Cp*)Cl(H-imam)]Cl (R-imam = N,N'-N(R)=C(Me)CH2C(Me)2NHR (18a)]. Complexes
      [Ir(Cp*)Cl(R-imam)]ClO4 (R = H (18b), Me (19)) are obtained from 18a and AgClO4
      or by refluxing 2b in acetone for 7 h, respectively. They react with AgClO4 and
      the appropriate neutral ligand or with [Ag(NH=CMe2)2]ClO4 to give [Ir(Cp*)(R
      imam)L](ClO4)2 (R = H, L = (t)BuNC (20), XyNC (21); R = Me, L = MeCN (22)) or
      [Ir(Cp*)(H-imam)(NH=CMe2)](ClO4)2 (23a), respectively. The later reacts with
      PPNCl to give [Ir(Cp*)(H-imam)(NH=CMe2)]Cl(ClO4) (23b). The reaction of 22 with
      XyNC gives [Ir(Cp*)(Me-imam)(CNXy)](ClO4)2 (24). The structures of complexes 15,
      16c and 18b have been solved by X-ray diffraction methods.

PMID- 18808116
TI  - Unambiguous identification of Mobius aromaticity for meso-aryl-substituted
      [28]hexaphyrins(1.1.1.1.1.1).
AB  - meso-Aryl-substituted [28]hexaphyrins(1.1.1.1.1.1) have been examined by (1)H,
      (13)C, and (19)F NMR spectroscopies, UV-vis absorption spectroscopy, magnetic
      circular dichroism spectroscopy, and single-crystal X-ray diffraction analysis.
      All of these data consistently indicate that [28]hexaphyrins(1.1.1.1.1.1) in
      solution at 25 degrees C exist largely as an equilibrium among several rapidly
      interconverting twisted Mobius conformations with distinct aromaticities, with a
      small contribution from a planar rectangular conformation with antiaromatic
      character at slightly higher energy. In the solid state,
      [28]hexaphyrins(1.1.1.1.1.1) take either planar or Mobius-twisted conformations,
      depending upon the meso-aryl substituents and crystallization conditions,
      indicating a small energy difference between the two conformers. Importantly,
      when the temperature is decreased to -100 degrees C in THF, these rapid
      interconversions among Mobius conformations are frozen, allowing the detection of
      a single [28]hexaphyrin(1.1.1.1.1.1) species having a Mobius conformation.
      Detailed analyses of the solid-state Mobius structures of compounds 2b, 2c, and
      2f showed that singly twisted structures are achieved without serious strain and
      that cyclic pi-conjugation is well-preserved, as needed for exhibiting strong
      diatropic ring currents. Actually, the harmonic-oscillator model for aromaticity
      (HOMA) values of these structures are significantly large (0.85, 0.69, and 0.71,
      respectively), confirming the first demonstration of stable Mobius aromatic
      systems consisting of free-base expanded porphyrins without the assistance of
      metal coordination.

PMID- 18808117
TI  - Enantioselective organocatalytic direct Michael addition of nitroalkanes to
      nitroalkenes promoted by a unique bifunctional DMAP-thiourea.
AB  - A new catalyst is designed, synthesized, and evaluated for the asymmetric Michael
      addition of nitroalkanes to nitroalkenes. The obdurate nature of this reaction
      has made this a formidable challenge to subdue by asymmetric catalysis. The
      catalyst design includes a thiourea function to activate the nitroalkene by a
      double H-bond and a 4-dimethylaminopyridine unit to deprotonate the nitroalkane
      and to bind the resulting nitronate anion also by a double H-bond. The chiral
      scaffold for the catalyst is 2,2'-diamino-1,1'-binaphthalene (BINAM), and a bis
      conjugate is prepared by the attachment of the thiourea unit and the
      dimethylaminopyridine moiety (DMAP) via the two amino groups. The resulting
      catalyst will effect the reaction of nitroalkanes to a variety of nitrostyrenes
      and gives excellent asymmetric inductions (91-95% ee) over a range of 10
      substrates. Remarkably, the asymmetric induction increases with decreasing
      catalyst loading with the optimal compromise between rate and induction at a
      loading of 2 mol %.

PMID- 18808118
TI  - Organocuprate conjugate addition: structural features of diastereomeric and
      supramolecular pi-intermediates.
AB  - In the reaction pathway of conjugate additions with organocuprate reagents, Cu(I)
      pi-complexes and Cu(III) sigma-complexes have been identified as central, NMR
      detectable intermediate species. However, no experimental evidence for the
      structures of pi-intermediates with extensive chiral enones or the principal
      aggregation level and aggregate structure of pi-complexes in diethyl ether has
      been available so far. Furthermore, the structural characteristics of pi
      complexes which are essential for their high reactivities and
      diastereoselectivities have not yet been rationalized experimentally. Therefore,
      the pi-intermediates of 4,4a,5,6,7,8-hexahydro-4a-methyl-naphthalen-2(3H)-one and
      Me2CuLi or Me2CuLi x LiX (X = I, CN) in diethyl ether are investigated in detail.
      For the first time, the formation of two intermediate cuprate enone pi-complexes
      on both sides of the double bond is observed. In addition, the conformation of
      the enone adopted in the major beta-face pi-complex rationalizes the exclusive
      syn addition observed in the synthetic product. For the investigation of the
      aggregation level and structure, a NMR screening of pi-complexes with Me2CuLi x
      LiX (X = I, CN) and three achiral enones is performed, which simplifies the
      spectra by the generation of enantiotopic pi-complexes. Thus, NMR diffusion
      experiments on cuprate intermediates and the detection of scalar couplings across
      copper without isotope labeling are possible for the first time. Extensive NMR
      studies, including those of cyclohexanone complexes, show that, in principle,
      salt-free dimethylcuprate is able to complex the carbonyl group. However, in the
      presence of salt, the carbonyl-complexing aggregates are composed of salt and
      cuprate moieties. These mixed aggregates cause the formation of large
      supramolecular pi-intermediate structures which control their reactivity. The pi
      complexing cuprate units show a bent geometry as a general structural feature
      that is unaffected by the presence or kind of salt and the type of enone. Thus,
      the high diastereoselectivity and the reactivity of organocuprate 1,4-addition
      reactions are for the first time rationalized on the basis of structural
      characteristics of selected pi-intermediates.

PMID- 18808120
TI  - Theoretical study of the oxygen exchange in uranyl hydroxide. An old riddle
      solved?
AB  - A multistep mechanism for the experimentally observed oxygen exchange [Inorg.
      Chem. 1999, 38, 1456] of UO2(2+) cations in highly alkaline solutions is
      suggested and probed computationally. It involves an equilibrium between
      [UO2(OH)4](2-) and [UO2(OH)5](3-), followed by formation of the stable [UO3(OH)3
      x H2O](3-) intermediate that forms from [UO2(OH)5](3-) through intramolecular
      water elimination. The [UO3(OH)3 x H2O](3-) intermediate facilitates oxygen
      exchange through proton shuttling, retaining trans-uranyl structures throughout,
      without formation of the cis-uranyl intermediates proposed earliar. Alternative
      cis-uranyl pathways have been explored but were found to have activation energies
      that are too high. Relativistic density functional theory (DFT) has been applied
      to obtain geometries and vibrational frequencies of the different species
      (reactants, intermediates, transition states, products) and to calculate reaction
      paths. Two different relativistic methods were used: a scalar four-component all
      electron relativistic method and the zeroeth-order regular approximation.
      Calculations were conducted for both gas phase and condensed phase, the latter
      treated using the COSMO continuum model. An activation energy of 12.5 kcal/mol is
      found in solution for the rate-determining step, the reaction of changing the
      four-coordinated uranyl hydroxide to the five-coordinated one. This compares
      favorably to the experimental value of 9.8 +/- 0.7 kcal/mol. Activation energies
      of 7.8 and 5.1 kcal/mol are found for the hydrogen transfer between equatorial
      and axial oxygens through a water molecule in [UO3(OH)3 x H2O](3-) in the gas
      phase and condensed phase, respectively. Contrary to previously proposed
      mechanisms that resulted in high activation barriers, we find energies that are
      low enough to facilitate the reaction at room temperature. For the activation
      energies, two approximate DFT methods, B3LYP and PBE, are compared. The
      differences in activation energies are only about 1-2 kcal/mol for these methods.

PMID- 18808121
TI  - Electronic structure and magnetism in transition metals doped 8-hydroxy-quinoline
      aluminum.
AB  - We report the room-temperature ferromagnetism in transition metals (Co, Ni)-doped
      8-hydroxy-quinoline aluminum (Alq3) by thermal coevaporation of high purity metal
      and Alq3 powders. For 5% Co-doped Alq3, a maximum magnetization of approximately
      0.33 microB/Co at 10 K was obtained and ferromagnetic behavior was observed up to
      300 K. The Co atoms interact chemically with O atoms and provide electrons to
      Alq3, forming new states acting as electron trap sites. From this, it is
      suggested that ferromagnetism may be associated with the strong chemical
      interaction of Co atoms and Alq3 molecules.

PMID- 18808119
TI  - Testing geometrical discrimination within an enzyme active site: constrained
      hydrogen bonding in the ketosteroid isomerase oxyanion hole.
AB  - Enzymes are classically proposed to accelerate reactions by binding substrates
      within active-site environments that are structurally preorganized to optimize
      binding interactions with reaction transition states rather than ground states.
      This is a remarkably formidable task considering the limited 0.1-1 A scale of
      most substrate rearrangements. The flexibility of active-site functional groups
      along the coordinate of substrate rearrangement, the distance scale on which
      enzymes can distinguish structural rearrangement, and the energetic significance
      of discrimination on that scale remain open questions that are fundamental to a
      basic physical understanding of enzyme active sites and catalysis. We bring
      together 1.2-1.5 A resolution X-ray crystallography, (1)H and (19)F NMR
      spectroscopy, quantum mechanical calculations, and transition-state analogue
      binding measurements to test the distance scale on which noncovalent forces can
      constrain the structural relaxation or translation of side chains and ligands
      along a specific coordinate and the energetic consequences of such geometric
      constraints within the active site of bacterial ketosteroid isomerase (KSI). Our
      results strongly suggest that packing and binding interactions within the KSI
      active site can constrain local side-chain reorientation and prevent hydrogen
      bond shortening by 0.1 A or less. Further, this constraint has substantial
      energetic effects on ligand binding and stabilization of negative charge within
      the oxyanion hole. These results provide evidence that subtle geometric effects,
      indistinguishable in most X-ray crystallographic structures, can have significant
      energetic consequences and highlight the importance of using synergistic
      experimental approaches to dissect enzyme function.

PMID- 18808122
TI  - Intramolecular anodic olefin coupling reactions: the use of a nitrogen trapping
      group.
AB  - Anodic olefin coupling reactions using a tosylamine trapping group have been
      studied. The cyclizations are favored by the use of a less-polar radical cation
      and more basic reaction conditions. The most significant factor for obtaining
      good yields of cyclic product is the use of the more basic reaction conditions.
      The cyclizations allow for the rapid synthesis of substituted proline
      derivatives.

PMID- 18808123
TI  - A versatile amino acid analogue of the solvatochromic fluorophore 4-N,N
      dimethylamino-1,8-naphthalimide: a powerful tool for the study of dynamic protein
      interactions.
AB  - We have developed a new unnatural amino acid based on the solvatochromic
      fluorophore 4-N,N-dimethylamino-1,8-naphthalimide (4-DMN) for application in the
      study of protein-protein interactions. The fluorescence quantum yield of this
      chromophore is highly sensitive to changes in the local solvent environment,
      demonstrating "switch-like" emission properties characteristic of the
      dimethylaminophthalimide family of fluorophores. In particular, this new species
      possesses a number of significant advantages over related fluorophores, including
      greater chemical stability under a wide range of conditions, a longer wavelength
      of excitation (408 nm), and improved synthetic accessibility. This amino acid has
      been prepared as an Fmoc-protected building block and may readily be incorporated
      into peptides via standard solid-phase peptide synthesis. A series of comparative
      studies are presented to demonstrate the advantageous properties of the 4-DMN
      amino acid relative to those of the previously reported 4-N,N
      dimethylaminophthalimidoalanine and 6-N,N-dimethylamino-2,3-naphthalimidoalanine
      amino acids. Other commercially available solvatochromic fluorophores are also
      include in these studies. The potential of this new probe as a tool for the study
      of protein-protein interactions is demonstrated by introducing it into a peptide
      that is recognized by calcium-activated calmodulin. The binding interaction
      between these two components yields an increase in fluorescence emission greater
      than 900-fold.

PMID- 18808124
TI  - A new total synthesis of patellamide A.
AB  - Patellamide A was efficiently synthesized from thiazole 2 via two complementary
      heterocyclization approaches to form the thiazole and oxazoline rings.

PMID- 18808126
TI  - Photogeneration of 2-deoxyribonolactone in benzophenone-purine dyads. Formation
      of ketyl-C1' biradicals.
AB  - Photolysis of the title dyads under aerobic conditions leads to a 2
      deoxyribonolactone derivative. Laser flash photolysis reveals that the process
      occurs from the short-lived benzophenone-like triplet excited state. A mechanism
      involving intramolecular electron transfer with the purine bases (adenine,
      guanine, or 8-oxoadenine) as donors is proposed.

PMID- 18808125
TI  - Convergent and general one-step DNA-catalyzed synthesis of multiply branched DNA.
AB  - We report a deoxyribozyme (DNA enzyme) that catalyzes the convergent and general
      synthesis of branched DNA. The 15HA9 deoxyribozyme mediates nucleophilic attack
      of the 2'-hydroxyl group of a ribonucleotide embedded within one DNA substrate
      into a 5'-adenylate of the second DNA substrate. This approach can be used to
      synthesize multiply branched DNA with a wide range of DNA sequences.

PMID- 18808127
TI  - An improved protocol for the Pd-catalyzed alpha-arylation of aldehydes with aryl
      halides.
AB  - An improved protocol for the Pd-catalyzed alpha-arylation of aldehydes with aryl
      halides has been developed. The new catalytic system allows for the coupling of
      an array of substrates including challenging electron-rich aryl bromides and less
      reactive aryl chlorides. The utility of this method has been demonstrated in a
      new total synthesis of (+/-)-sporochnol.

PMID- 18808129
TI  - Synthesis of macrocycle isomers via metathesis cyclization and their self
      assembly from aqueous solutions.
AB  - Novel triangular macrocycle isomers were synthesized through metathesis
      cyclization with high yield (77%). HPLC and MALDI-TOF showed that the purity of
      the macrocycles was higher than 99%, while (1)H NMR clearly showed that these
      macrocycles contain C2 and C3 isomers in a ratio of 1:3. AFM and TEM showed that
      they spontaneously formed vesicular structures in a chloroform/water system with
      an average diameter of 460 nm, which was corroborated by DLS results.

PMID- 18808128
TI  - Studies on the synthesis of durhamycin A: stereoselective synthesis of a model
      aglycone.
AB  - A stereoselective synthesis of the model aglycone corresponding to the anti-HIV
      aureolic acids durhamycins A (1) and B (2) is described.

PMID- 18808130
TI  - Palladium-catalyzed benzylic arylation of N-benzylxanthone imine.
AB  - The direct benzylic arylation of N-benzylxanthone imine with aryl chloride
      proceeds under palladium catalysis, yielding the corresponding coupling product.
      The product is readily transformed to benzhydrylamine. Taking into consideration
      that the imine is readily available from benzylic amine, the overall
      transformation represents a formal cross-coupling reaction of aryl halide with
      alpha-aminobenzyl metal.

PMID- 18808131
TI  - General, stereoselective synthesis of (Z)-beta,gamma-unsaturated nitriles
      promoted by samarium diiodide.
AB  - A method to obtain (Z)-beta,gamma-unsaturated nitriles in high or good yields and
      with moderate or high stereoselectivity is described. The products were achieved
      through the photoinduced metalation of 3-acetoxy-4-chloronitriles with SmI2. The
      starting compounds were readily prepared, and a mechanism is proposed to explain
      this stereoselective beta-elimination reaction.

PMID- 18808132
TI  - Nickel-catalyzed borylative ring-opening reaction of vinylcyclopropanes with
      bis(pinacolato)diboron yielding allylic boronates.
AB  - Vinylcyclopropanes bearing one or two electron-withdrawing groups on the
      cyclopropane ring undergo nickel-catalyzed borylative ring opening with
      bis(pinacolato)diboron to yield allylic boronates. The reaction proceeded with
      high E selectivity.

PMID- 18808133
TI  - Facile preparation of alpha-aryl nitriles by direct cyanation of alcohols with
      TMSCN under the catalysis of InX3.
AB  - A convenient and efficient synthesis of alpha-aryl nitriles was developed by
      direct cyanation of alcohols with TMSCN under the catalysis of Lewis acid. Using
      5-10 mol % of InBr3 as the catalyst, a variety of benzylic alcohols can be
      converted to the corresponding nitriles in 5-30 min with yields of 46-99%.

PMID- 18808134
TI  - A light-harvesting array composed of porphyrins and rigid backbones.
AB  - A light-harvesting array containing rigid backbones, peripherally positioned Zn
      porphyrin terminals, and a free-base (Fb) porphyrin core was prepared by a
      convergent method where the Sonogashira coupling reaction was used in the key
      steps. Effective intramolecular singlet-energy transfer from the peripheral Zn
      porphyrin units to the Fb porphyrin core was observed. The efficiency of the
      energy transfer was compared with those of reference compounds.

PMID- 18808135
TI  - The first synthesis of a thioglycoside analogue of the immunostimulant KRN7000.
AB  - The first total synthesis of a thioglycoside analogue of KRN7000, a potential
      immunostimulant, is described. Two key intermediates are alpha-galactosyl thiol 4
      and phytosphingosine derivative 5, which were both prepared from D-galactose.

PMID- 18808136
TI  - Platinum-catalyzed enantioselective tandem alkylation/arylation of primary
      phosphines. Asymmetric synthesis of P-stereogenic 1-phosphaacenaphthenes.
AB  - Enantioselective tandem alkylation/arylation of primary phosphines with 1-bromo-8
      chloromethylnaphthalene catalyzed by Pt(DuPhos) complexes gave P-stereogenic 1
      phosphaacenaphthenes (AcePhos) in up to 74% ee. Diastereoselective formation of
      four P-C bonds in one pot with bis(primary) phosphines gave C2-symmetric
      diphosphines, including the o-phenylene derivative DuAcePhos, for which the rac
      isomer was formed with high enantioselectivity. These reactions, which appear to
      proceed via an unusual metal-mediated nucleophilic aromatic substitution pathway,
      yield a new class of heterocycles with potential applications in asymmetric
      catalysis.

PMID- 18808137
TI  - N-(p-dodecylphenylsulfonyl)-2-pyrrolidinecarboxamide: a practical proline mimetic
      for facilitating enantioselective aldol reactions.
AB  - A highly practical and readily available proline surrogate has been developed
      with improved solubility properties in common, nonpolar organic solvents. This
      sulfonamide-based catalyst has proven highly effective at facilitating
      enantioselective and diastereoselective aldol reactions with a range of
      substrates in nonpolar organic solvents in the presence of a single equivalent of
      water. Additionally, catalyst loading as low as 2 mol % can be employed in the
      absence of any organic solvent with continued high levels of selectivity.

PMID- 18808138
TI  - Microwave-assisted palladium-catalyzed cross-coupling of aryl and vinyl halides
      with H-phosphonate diesters.
AB  - A general and efficient method for the microwave-assisted formation of the C-P
      bond was developed. Using a prevalent palladium catalyst, Pd(PPh3)4, a
      quantitative cross-coupling of various H-phosphonate diesters with aryl and vinyl
      halides was achieved in less than 10 min. The reactions occurred with retention
      of configuration at the phosphorus center and in the vinyl moiety. Using this
      protocol, several C-phosphonates, including those bearing nucleoside and
      cholesteryl moieties, were prepared in high yields.

PMID- 18808139
TI  - Influence of the glycosylation of human salivary proline-rich proteins on their
      interactions with condensed tannins.
AB  - Binding of condensed tannins to salivary proteins is supposed to be involved in
      their astringency. First, complexes arising from the interaction of saliva from
      two individuals and tannins were studied. Then interaction mixture models
      containing purified saliva proteins were developed. The highest polymerized
      tannins predominantly precipitated together with the salivary proteins.
      Electrophoresis of proteins in combination with thiolysis analysis of tannins
      indicated proline-rich protein (PRP)-polyphenol complexes in precipitated
      fractions and also in the soluble ones with individual differences. Individual
      salivas exhibiting different protein patterns were discriminated with regard to
      their ability to interact with tannins. From binding studies with purified
      classes of salivary proteins, interactions were shown to depend on the nature of
      the protein, in particular on their glycosylation state. For low concentrations
      of tannins, glycosylated PRP-tannin interactions led to complexes that remained
      soluble, whereas those arising from nonglycosylated PRP-tannin interactions were
      precipitated. This finding could indicate that under physiological conditions,
      complexes involving glycosylated proteins maintain part of the lubrication of the
      oral cavity, whereas tannin trapping leads to a lower astringency perception.

PMID- 18808140
TI  - Synthesis and phytotoxic activity of ozonides.
AB  - The [4 + 3] cycloaddition of the proper furans with the oxyallyl cation,
      generated in situ from 2,4-dibromopentan-3-one, produced a series of 8-oxabicyclo
      [3.2.1]oct-6-en-3-ones. Exposure of the oxabicycles to ozone afforded the
      corresponding 8,9,10,11-tetraoxatricyclo[5.2.1.1 (2,6)]undecan-4-ones in variable
      yields (7-100%). The phytotoxic properties of these ozonides (or 1,2,4
      trioxolanes) and their oxabicycle precursors were evaluated as the ability to
      interfere with the growth of Sorghum bicolor and Cucumis sativus seedlings. Among
      oxabicycles, the highest inhibitory activity was shown by compounds possessing a
      alpha,beta-unsaturated carbonyl moiety. A differential sensitivity of the two
      crops was evident with ozonides. The most active compounds were also tested
      against the weed species Ipomoea grandifolia and Brachiaria decumbens. To the
      best of our knowledge, this is the first article describing ozonides as potential
      herbicides.

PMID- 18808141
TI  - Spatial distribution and characterization of long-term aged 14C-labeled atrazine
      residues in soil.
AB  - The long-term behavior of the herbicide atrazine and its metabolites in the
      environment is of continued interest in terms of risk assessment and soil quality
      monitoring. Aqueous desorption, detection, and quantification of atrazine and its
      metabolites from an agriculturally used soil were performed 22 years after the
      last atrazine application. A lysimeter soil containing long-term aged atrazine
      for >20 years was subdivided into 10 and 5 cm layers (at the lysimeter bottom:
      soil 0-50 and 50-55 cm; fine gravel 55-60 cm depth, implemented for drainage
      purposes) to identify the qualitative and quantitative differences of aged (14)C
      labeled atrazine residues depending on the soil profile and chemico-physical
      conditions of the individual soil layers. Deionized water was used for
      nonexhaustive cold water shaking extraction of the soil. With increasing soil
      depth, the amount of previously applied (14)C activity decreased significantly
      from 8.8% to 0.7% at 55-60 cm depth whereas the percentage of desorbed (14)C
      residues in each soil layer increased from 2% to 6% of the total (14)C activity
      in the sample. The only metabolite detectable by means of LC-MS/MS was 2
      hydroxyatrazine while most of the residual (14)C activity was bound to the soil
      and was not desorbed. The amount of desorbed 2-hydroxyatrazine decreased with
      increasing soil depth from 21% to 10% of the total desorbed (14)C residue
      fraction. The amount of (14)C residues in the soil layers correlated well with
      the carbon content in the soil and in the aqueous soil extracts ( p value = 0.99
      and 0.97, respectively), which may provide evidence of the binding behavior of
      the aged atrazine residues on soil carbon. The lowest coarse layer (55-60 cm)
      showed increased residual (14)C activity leading to the assumption that most
      (14)C residues were leached from the soil column over time.

PMID- 18808142
TI  - Detection of high molecular weight glutenin subunits in triticale (x
      Triticosecale Wittm.) Cultivars by capillary zone electrophoresis.
AB  - An improved method for separating and characterizing high molecular weight
      glutenin subunits (HMW-GS) in hexaploid triticale by capillary zone
      electrophoresis (CZE) was developed. A low-concentrate mixture of hydrophilic
      polymers, poly(vinylpyrrolidone) (PVP) and hydroxypropylmethylcellulose (HPMC),
      in an isoelectric buffer was employed for dynamic coating of the capillary inner
      wall. In separation buffer PVP with lower concentrated poly(ethylene oxide) (PEO)
      was replaced. The CZE electropherograms of HMW-GS showed two group peaks in
      accordance with x- and y-type subunits with migration times of 6.8-7.8 and 8.4
      11.5 min, respectively. In total, 14 HMW subunits (2 subunits encoded by Glu-A1
      locus and 12 by Glu-B1) were identified. The CZE analyses revealed that each of
      the subunits Bx7 and By8 determined by SDS-PAGE makes up three subunits (Bx6.8,
      Bx7, and Bx7* and By8, By8*, and new By8**, respectively), with different
      migration times. It was also shown that the subunits By18 and By20 in triticale
      determined by SDS-PAGE have different migration times in comparison with the same
      subunits in bread wheat. For these new HMW-GS, the following names were assigned:
      By18* instead of By18 and By20* instead of By20. The presented CZE method is an
      efficient alternative to the SDS-PAGE procedure for early selection of useful
      triticale genotypes with good breadmaking quality.

PMID- 18808143
TI  - Angiotensin I-converting enzyme-inhibitory peptides obtained from chicken
      collagen hydrolysate.
AB  - In this study, collagen extracted from chicken legs (which are the yellow keratin
      parts containing a nail) was hydrolyzed with various enzymes, and the angiotensin
      I-converting enzyme (ACE)-inhibitory activity of each hydrolysate was determined.
      The hydrolysate by treatment with an Aspergillus species-derived enzyme had the
      highest activity (IC 50 = 260 microg/mL). The fraction of this hydrolysate
      obtained by ultrafiltration with a molecular-weight cutoff of 3000 Da (low
      fraction) had a stronger activity (IC 50 = 130 microg/mL) than the fractionated
      one. This fraction was further fractionated by HPLC, and the peptides in the
      fraction with high ACE-inhibitory activity were identified. The amino acid
      sequences of the four peptides were identified using a protein sequencer. These
      peptides were synthesized to confirm their ACE-inhibitory activities; this showed
      that peptides with a Gly-Ala-Hyp-Gly-Leu-Hyp-Gly-Pro sequence had the highest
      activity (IC 50 = 29 microM). When the low fraction was administered to
      spontaneous hypertensive rats, a decrease in their blood pressure was observed
      after 2 h of administration, and a significant decrease in blood pressure (-50
      mmHg) was observed after 6 h. Moreover, long-term administration studies
      indicated that the low fraction showed a significant suppression of increased
      blood pressure.

PMID- 18808144
TI  - Novel protoporphyrinogen oxidase inhibitors: 3H-pyrazolo[3,4-d][1,2,3]triazin-4
      one derivatives.
AB  - A series of 3 H-pyrazolo[3,4-d][1,2,3]triazin-4-one derivatives were synthesized
      as candidate herbicides by diazotization of different 5(3)-amino- N-phenyl-1 H
      pyrazole-4-carboxamide derivatives prepared by the reaction of substituted 5(3)
      amino-pyrazole-4-carbonyl chloride with a substituted aniline. Their structures
      were identified by (1)H NMR and elemental analyses. The isomers D and E were
      isolated, and their structures were identified by two-dimensional NMR analyses
      (heteronuclear single quantum coherence and heteronuclear multiple-bond
      correlation) and single-crystal X-ray diffraction analysis. The bioassay results
      showed that some of the title compounds exhibited both excellent herbicidal
      activity at a dose of 93.75 g/ha and strong inhibition against protoporphyrinogen
      oxidase activity in vitro. The structure-activity relationship showed that D16
      possessed the highest activities both in vivo and in vitro when the N-substituted
      group of the pyrazole ring was allyl and the N-substituted group of
      benzooxazinone was propargyl.

PMID- 18808145
TI  - Evaluation of the combined effects of enzymatic treatment and aging on lees on
      the aroma of wine from Bombino bianco grapes.
AB  - In this study, two different doses of commercial beta-glucanase enzyme
      preparation were tested to verify their effect on wines aged on lees. These wines
      were compared with two samples with no enzymatic treatment. The former was aged
      on lees (control), and the latter was readily filtered off from the yeast cell
      biomass (standard). Analysis of variance (one-way ANOVA), the Tukey test, and
      principal component analysis (PCA) were applied to all of the samples, which were
      analyzed for aroma composition, along with galacturonic acid, total acidity, pH,
      and color. Results showed a large number of statistically significant differences
      among samples. In general, wines treated with beta-glucanase were characterized
      by higher concentration of many volatile compounds. The presence of lees and even
      more the exogenous enzymatic action enhanced almost all volatile compounds.
      Besides the high presence of ethyl esters, it is worth mentioning the behavior of
      hexanol and trans-3-hexenol, which are strongly enhanced by the presence of lees
      and by enzymatic treatments.

PMID- 18808146
TI  - Black soybean promotes the formation of active components with antihepatoma
      activity in the fermentation product of Agaricus blazei.
AB  - The antihepatoma activity and related active components in the fermentation
      products of Agaricus blazei (AB) cultured in the medium containing soybean (S) or
      black soybean (BS) were investigated. AB(BS)-pE and AB(S)-pE were the ethanolic
      extracts from the fermentation products of AB(BS) and AB(S), respectively.
      According to the IC 50 values, AB(BS)-pE (161.1 and 24.0 microg/mL for Hep 3B and
      Hep G2 cells, respectively) exhibited stronger cytotoxicities against hepatoma
      cells than AB(S)-pE (>200 and 99.9 microg/mL for Hep 3B and Hep G2 cells,
      respectively). AB(BS)-pE was separated by silica gel column chromatography and
      eluted with n-hexane/ethyl acetate/methanol gradient solvent system into 21
      fractions. Fraction 3 [AB(BS)-pE-F3], eluted with n-hexane/ethyl acetate (97:3
      and 19:1, v/v), was the most active fraction having inhibitory activity on the
      proliferation of Hep 3B and Hep G2 cells (IC 50 of 3.6 and 1.9 microg/mL,
      respectively). Three major compounds, compounds 1- 3, were further isolated from
      the AB(BS)-pE-F3 fraction by reversed-phase semipreparative high-performance
      liquid chromatography. Compounds 2 and 3 gave better antihepatoma activity than
      that of compound 1. The IC 50 values of compounds 2 and 3 were 2.8 and 4.5
      microg/mL for Hep 3B cells and 1.4 and 2.0 microg/mL for Hep G2 cells,
      respectively. The structures of compounds 2 and 3 were identified by UV, IR,
      electron impact mass spectrometry, and (1)H and (13)C NMR to be blazeispirols A
      and C, respectively. Blazeispirols A and C existed in the mycelia but not in the
      broth and were more in AB(BS)-pE (49.9 +/- 8.9 and 14.2 +/- 2.4 mg/g,
      respectively) than AB(S)-pE (15.9 +/- 1.7 and 3.9 +/- 0.6 mg/g, respectively).
      Additionally, the result shows that the production of blazeispirols A and C was
      increased after cultivation in the medium containing black soybean on day 6 and
      reached the maximum on day 12, and the contents of blazeispirols A and C were
      negatively correlated with Hep 3B and Hep G2 cell viabilities ( r = -0.84 to 
      0.93, P < 0.01). It suggests that blazeispirols A and C could be used as
      biomarkers to produce the fermentation product of A. blazei with antihepatoma
      activity.

PMID- 18808148
TI  - Rearrangement of partially ordered stacked conformations contributes to the
      rugged energy landscape of a small RNA hairpin.
AB  - We have studied the fast relaxation kinetics of a small RNA hairpin tetraloop
      using time-resolved infrared spectroscopy. A laser-induced temperature jump
      initiated the relaxation by rapidly perturbing the thermal equilibrium of the
      sample. We probed the relaxation kinetics at two different wavenumbers, 1574 and
      1669 cm (-1). The latter is due to the C6O6 carbonyl stretch of the base guanine
      and is a direct measure of guanine base pairing. The former is assigned to a ring
      vibration of guanine and tracks structure by sensing base stacking interactions.
      Overall, the kinetics at 1574 cm (-1) are faster than those observed at 1669 cm (
      1). When relaxation occurs at the melting temperature, the kinetics at both
      wavenumbers are biexponential. When relaxation occurs at a temperature that is
      higher than the melting temperature, the data at 1669 cm (-1) are still
      biexponential while only a single fast phase is resolved in the data at 1574 cm (
      1). The fast phases are in the range of microseconds, while the slower phases are
      in the range of tens of microseconds. At both wavenumbers, a portion of the
      relaxation is not resolved, indicating the existence of a very fast, sub-100 ns
      phase. Our results provide additional evidence that small, fast folding hairpin
      loops are characterized by a rugged energy landscape. Furthermore, our data
      suggest that single-strand stacking interactions and stacking interactions in the
      loop contribute significantly to the ruggedness of the energy landscape. This
      work also demonstrates the utility of time-resolved infrared spectroscopy in
      studying RNA folding.

PMID- 18808149
TI  - Structures of Trypanosoma cruzi dihydroorotate dehydrogenase complexed with
      substrates and products: atomic resolution insights into mechanisms of
      dihydroorotate oxidation and fumarate reduction.
AB  - Dihydroorotate dehydrogenase (DHOD) from Trypanosoma cruzi (TcDHOD) is a member
      of family 1A DHOD that catalyzes the oxidation of dihydroorotate to orotate
      (first half-reaction) and then the reduction of fumarate to succinate (second
      half-reaction) in the de novo pyrimidine biosynthesis pathway. The oxidation of
      dihydroorotate is coupled with the reduction of FMN, and the reduced FMN converts
      fumarate to succinate in the second half-reaction. TcDHOD are known to be
      essential for survival and growth of T. cruzi and a validated drug target. The
      first-half reaction mechanism of the family 1A DHOD from Lactococcus lactis has
      been extensively investigated on the basis of kinetic isotope effects,
      mutagenesis and X-ray structures determined for ligand-free form and in complex
      with orotate, the product of the first half-reaction. In this report, we present
      crystal structures of TcDHOD in the ligand-free form and in complexes with an
      inhibitor, physiological substrates and products of the first and second half
      reactions. These ligands bind to the same active site of TcDHOD, which is
      consistent with the one-site ping-pong Bi-Bi mechanism demonstrated by kinetic
      studies for family 1A DHODs. The binding of ligands to TcDHOD does not cause any
      significant structural changes to TcDHOD, and both reduced and oxidized FMN
      cofactors are in planar conformation, which indicates that the reduction of the
      FMN cofactor with dihydroorotate produces anionic reduced FMN. Therefore, they
      should be good models for the enzymatic reaction pathway of TcDHOD, although
      orotate and fumarate bind to TcDHOD with the oxidized FMN and dihydroorotate with
      the reduced FMN in the structures determined here. Cys130, which was identified
      as the active site base for family 1A DHOD (Fagan, R. L., Jensen, K. F.,
      Bjornberg, O., and Palfey, B. A. (2007) Biochemistry 46, 4028-4036.), is well
      located for abstracting a proton from dihydroorotate C5 and transferring it to
      outside water molecules. The bound fumarate is in a twisted conformation, which
      induces partial charge separation represented as C 2 (delta-) and C 3 (delta+).
      Because of this partial charge separation, the thermodynamically favorable
      reduction of fumarate with reduced FMN seems to proceed in the way that C 2
      (delta-) accepts a proton from Cys130 and C 3 (delta+) a hydride (or a hydride
      equivalent) from reduced FMN N 5 in TcDHOD.

PMID- 18808150
TI  - Autoxidation of the site-specifically PEGylated hemoglobins: role of the PEG
      chains and the sites of PEGylation in the autoxidation.
AB  - The PEGylated hemoglobin (Hb) has been evaluated as a potential blood substitute.
      In an attempt to understand the autoxidation of the PEGylated Hb, we have studied
      the autoxidation of the PEGylated Hb site-specifically modified at Cys-93(beta)
      or at Val-1(beta). PEGylation of Hb at Cys-93(beta) perturbed the heme
      environment and increased the autoxidation rate of Hb, which is at a higher level
      than that caused by PEGylation at Val-1(beta). The perturbation of the heme
      environment of Hb is attributed to the maleimide modification at Cys-93(beta) and
      not due to conjugation of the PEG chains. However, the PEG chains enhance the
      autoxidation and the H 2O 2 mediated oxidation of Hb. Accordingly, the PEG chains
      are assumed to increase the water molecules in the hydration layer of Hb and
      enhance the autoxidation by promoting the nucleophilic attack of heme. The
      autoxidation rate of the PEGylated Hb does not show an inverse correlation with
      the oxygen affinity. The H 2O 2 mediated structural loss and the heme loss of Hb
      are increased by maleimide modification at Cys-93(beta) and further decreased by
      conjugation of the PEG chains. The autoxidation of the PEGylated Hbs is
      attenuated significantly in the plasma, possibly due to the presence of the
      antioxidant species in the plasma. This result is consistent with the recent
      suggestion that there is no direct correlation between the in vitro and in vivo
      autoxidation of the PEGylated Hb. Therefore, the pattern of PEGylation can be
      manipulated for the design of the PEGylated Hb with minimal autoxidation.

PMID- 18808151
TI  - Optimizing identification and quantitation of 15N-labeled proteins in comparative
      proteomics.
AB  - Comparative proteomics has emerged as a powerful approach to determine
      differences in protein abundance between biological samples. The introduction of
      stable-isotopes as internal standards especially paved the road for quantitative
      proteomics for comprehensive approaches to accurately determine protein dynamics.
      Metabolic labeling with (15)N isotopes is applied to an increasing number of
      organisms, including Drosophila, C. elegans, and rats. However, (15)N-enrichment
      is often suboptimal (<98%), which may hamper identification and quantitation of
      proteins. Here, we systematically investigated two independent (15)N-labeled data
      sets to explore the influence of heavy nitrogen enrichment on the number of
      identifications as well as on the error in protein quantitation. We show that
      specifically larger (15)N-labeled peptides are under-represented when compared to
      their (14)N counterparts and propose a correction method, which significantly
      increases the number of identifications. In addition, we developed a method that
      corrects for inaccurate peptide ratios introduced by incomplete (15)N enrichment.
      This results in improved accuracy and precision of protein quantitation.
      Altogether, this study provides insight into the process of protein
      identification and quantitation, and the methods described here can be used to
      improve both qualitative and quantitative data obtained by labeling with heavy
      nitrogen with enrichment less than 100%.

PMID- 18808152
TI  - Ultralow fouling and functionalizable surface chemistry based on a zwitterionic
      polymer enabling sensitive and specific protein detection in undiluted blood
      plasma.
AB  - A crucial step in the development of implanted medical devices, in vivo
      diagnostics, and microarrays is the effective prevention of nonspecific protein
      adsorption from real-world complex media such as blood plasma or serum. In this
      work, a zwitterionic poly(carboxybetaine acrylamide) (polyCBAA) biomimetic
      material was employed to create a unique biorecognition coating with an ultralow
      fouling background, enabling the sensitive and specific detection of proteins in
      blood plasma. Conditions for surface activation, protein immobilization, and
      surface deactivation of the carboxylate groups in the polyCBAA coating were
      determined. An antibody-functionalized polyCBAA surface platform was used to
      detect a target protein in blood plasma using a sensitive surface plasmon
      resonance (SPR) sensor. A selective protein was directly detected from 100% human
      blood plasma with extraordinary specificity and sensitivity. The total
      nonspecific protein adsorption on the functionalized polyCBAA surface was very
      low (<3 ng/cm (2) for undiluted blood plasma). Because of the significant
      reduction of nonspecific protein adsorption, it was possible to monitor the
      kinetics of antigen-antibody interactions in undiluted blood plasma. The
      functionalization effectiveness and detection characteristics using a cancer
      protein marker candidate of polyCBAA were compared with those of the conventional
      nonfouling oligo(ethylene glycol)-based surface chemistry.

PMID- 18808153
TI  - Two-laser, large-field hyperspectral microarray scanner for the analysis of
      multicolor microarrays.
AB  - We describe the development and operation of a two-laser, large-field
      hyperspectral scanner for analysis of multicolor genotyping microarrays. In
      contrast to confocal microarray scanners, in which wavelength selectivity is
      obtained by positioning band-pass filters in front of a photomultiplier detector,
      hyperspectral microarray scanners collect the complete visible emission spectrum
      from the labeled microarrays. Hyperspectral scanning permits discrimination of
      multiple spectrally overlapping fluorescent labels with minimal use of optical
      filters, thus offering important advantages over standard filter-based multicolor
      microarray scanners. The scanner uses two-sided oblique line illumination of
      microarrays. Two lasers are used for the excitation of dyes in the visible and
      near-infrared spectral regions. The hyperspectral scanner was evaluated with
      commercially available two-color calibration slides and with in-house-printed
      four-color microarrays containing dyes with spectral properties similar to their
      commercial genotyping array counterparts.

PMID- 18808154
TI  - Single-shot biodiesel analysis: nearly instantaneous typification and quality
      control solely by ambient mass spectrometry.
AB  - Using a simple and easily implemented desorption/ionization mass spectrometry
      technique, a tiny droplet of biodiesel placed on the surface of a sheet of paper
      is analyzed directly and nearly instantaneously under ambient conditions. No pre
      separation or sample preparation is required, and clean mass spectra are obtained
      with great simplicity. In the positive ion mode, easy ambient sonic-spray
      ionization mass spectrometry, EASI(+)-MS, provides typical profiles of the major
      components of biodiesel samples, that is, either methyl esters (FAME) or ethyl
      esters (FAEE) of the natural fatty acids and triglycerides (TAG) from residual
      oil or oil from adulteration. Each FAME (FAEE) or TAG molecule is detected as a
      single sodiated molecule, [M + Na] (+) with relative intensities that correlate
      well with the known fatty acid profiles of the oil. Using EASI(-)-MS, typical and
      complementary profiles of free fatty acids (FFA) are obtained, which are detected
      in their deprotonated forms [FAA - H] (-). A general, single-shot approach for
      biodiesel analysis is therefore described, and samples from different feedstocks,
      from blends with petrodiesel, or from either methanol or ethanol trans
      esterification are readily typified and major parameters of quality accessed.

PMID- 18808155
TI  - Determination of unbiased selectivity coefficients using pulsed
      chronopotentiometric polymeric membrane ion sensors.
AB  - A new procedure for the determination of selectivity coefficients of neutral
      carriers using pulsed chronopotentiometric ion selective sensors (pulstrodes) is
      established. Pulstrode membrane which lacks an ion-exchanger suppresses the zero
      current ion flux, allowing a Nernstian response slope for even highly
      discriminated ions. Unlike previously developed methods, unbiased selectivity
      remains unaltered even with the exposure to the primary ion solution for
      prolonged time. Studies with potassium-, silver-, and calcium-selective
      electrodes reveal that pulstrodes yield the same or slightly favorable unbiased
      selectivity coefficients than reported earlier. In contrast to alternative
      methods for the determination of unbiased selectivity, this technique offers a
      unique simplicity and reliability. Therefore the new procedure promises to be a
      valuable additional tool for the characterization of unbiased selectivity
      coefficients for the ISEs.

PMID- 18808156
TI  - Advanced glycation end products of DNA: quantification of N2-(1-Carboxyethyl)-2'
      deoxyguanosine in biological samples by liquid chromatography electrospray
      ionization tandem mass spectrometry.
AB  - Methylglyoxal (MG) and related alpha-oxoaldehydes react with proteins, lipids,
      and DNA to give rise to covalent adducts known as advanced glycation end products
      (AGEs). Elevated levels of AGEs have been implicated in the pathological
      complications of diabetes, uremia, Alzheimer's disease, and possibly cancer.
      There is therefore widespread interest in developing sensitive methods for the in
      vivo measurement of AGEs as prognostic biomarkers and for treatment monitoring.
      The two diastereomeric MG-DNA adducts of N(2)-(1-carboxyethyl)-2'-deoxyguanosine
      (CEdG) are the primary glycation products formed in DNA; however, accurate
      assessment of their distribution in vivo has not been possible since there is no
      readily available quantitative method for CEdG determination in biological
      samples. To address these issues, we have developed a sensitive and quantitative
      liquid chromatography electrospray ionization tandem mass spectrometry assay
      using the stable isotope dilution method with an (15)N(5)-CEdG standard. Methods
      for CEdG determination in urine or tissue extracted DNA are described. Changes in
      urinary CEdG in diabetic rats in response to oral administration of the AGE
      inhibitor LR-90 are used to demonstrate the potential utility of the method for
      treatment monitoring. Both stereoisomeric CEdG adducts were detected in a human
      breast tumor and normal adjacent tissue at levels of 3-12 adducts/10(7) dG,
      suggesting that this lesion may be widely distributed in vivo. Strategies for
      dealing with artifactual adduct formation due to oxoaldehyde generation during
      DNA isolation and enzymatic workup procedures are described.

PMID- 18808157
TI  - Reduction with glutathione is a weakly mutagenic pathway in chromium(VI)
      metabolism.
AB  - Although reductive metabolism of Cr(VI) always results in the production of
      Cr(III) and extensive Cr-DNA binding, cellular studies have indicated that
      different reduction processes are not equivalent in the induction of mutagenic
      events. Here, we examined mutagenicity and formation of Cr-DNA damage by Cr(VI)
      activated in vitro by one of its important reducers, glutathione (GSH). Our main
      focus was on reactions containing 2 mM GSH, corresponding to its average
      concentration in CHO (1.8 mM) and V79 (2.6 mM) mutagenicity models. We found that
      Cr(VI) reduction by 2 mM GSH produced only weak mutagenic responses in pSP189
      plasmids replicated in human fibroblasts. Reductive activation of Cr(VI) with 5
      mM GSH resulted in approximately 4-times greater DNA adduct-normalized yield of
      mutations. Mutagenic DNA damage formed in GSH-chromate reactions was caused by
      nonoxidative mechanisms, as blocking of Cr-DNA adduction led to a complete loss
      of mutagenesis. All GSH-mediated reactions also lacked significant DNA single
      strand breakage. We developed a sensitive HPLC procedure for the detection of GSH
      Cr-DNA cross-links based on the dissociation of DNA-conjugated GSH by Cr(III)
      chelation and its derivatization with monobromobimane. Weak mutagenicity of 2 mM
      GSH reactions was associated with a low production of mutagenic GSH-Cr-DNA cross
      links (5.0% of total Cr-DNA adducts). In agreement with their greater mutation
      inducing ability, 5 mM GSH reactions generated 4-5 times higher levels of GSH-DNA
      cross-linking. Overall, our results indicate that chromate reduction by
      physiological concentrations of GSH is a weakly mutagenic process, which is
      consistent with low mutagenicity of Cr(VI) in ascorbate-deficient cells.

PMID- 18808159
TI  - Helical tubuland diols: a synthetic and crystal engineering quest.
AB  - Despite many advances in recent years, crystal engineering remains a risky
      venture. A successful outcome requires manipulation of the noncovalent bonding
      and properties such as size, shape, repulsion, attraction, polarity, and
      chirality. In this Account, we describe the interplay of crystal engineering and
      synthetic organic chemistry required to develop the family of helical tubuland
      diol hosts, the members of which exhibit a wide range of tube dimensions and
      inclusion properties. Certain alicyclic dialcohols crystallize with a hydrogen
      bonded network structure, termed the helical tubuland lattice, in space group
      P3(1)21 (or its enantiomorph P3(2)21). Double helices of diol molecules surround
      parallel tubes that contain guest molecules, which are included on the basis of
      size and shape rather than functional group. The crystal structure of
      (diol)(3).(chloroacetic acid)(1.2) is illustrative. These chiral helical tubulate
      lattice inclusion compounds are formed when the racemic host diol is allowed to
      crystallize from solution. Complete enantiomer separation occurs during this
      process, producing a 1:1 mixture of pure (+)- and pure (-)-crystals (a
      conglomerate). The challenge of creating this family of compounds required the
      development of much synthetic chemistry, in particular new pathways to alicyclic
      ring systems with specific substitution patterns. It was also necessary to
      understand and control the supramolecular properties of the diol molecules. What
      makes the original compound tick, and why did it behave in this remarkable
      manner, when most of its structural neighbors crystallize totally differently?
      The synthesis of new helical tubuland diols requires not just preparation of a
      new molecular structure but also a transplant of the original unchanged hydrogen
      bonding supramolecular synthon. Synthesis of the specific crystal space group is
      necessary. This was achieved by defining structural characteristics, termed
      molecular determinants, which are essential for the helical tubuland structure to
      occur. If these requirements were met, then the target molecule had a high
      probability of success. This investigation has close conceptual parallels with
      the search for pharmacophore properties of bioactive molecules. In both
      situations, parts of a molecule with little or no chemical reactivity may
      actually play vital supramolecular roles. The review illustrates how crystal
      engineering is based on specific supramolecular properties that can be uncovered
      and then exploited by synthetic chemists.

PMID- 18808158
TI  - Angelica sinensis and its alkylphthalides induce the detoxification enzyme
      NAD(P)H: quinone oxidoreductase 1 by alkylating Keap1.
AB  - The roots of Angelica sinensis (Oliv.) Diels (Dang Gui; Apiaceae) have a long
      history in traditional Chinese medicine as a remedy for women's disorders and are
      often called "lady's ginseng". Currently, extracts of A. sinensis are commonly
      included in numerous dietary supplements used for women's health and as antiaging
      products. In the present study, we examined the potential chemopreventive
      activity of A. sinensis extracts by measuring the relative ability to induce the
      detoxification enzyme, NAD(P)H:quinone oxidoreductase 1 (NQO1). The lipophilic
      partitions showed strong NQO1 induction with concentrations to double the enzyme
      activity (CD) of 5.5 +/- 0.7 (petroleum ether) and 3.9 +/- 0.5 microg/mL
      (chloroform). Fractionation led to the isolation of phenolic esters and
      alkylphthalides, especially Z-ligustilide, the main lipophilic compound, which
      showed strong NQO1 inducing properties (CD = 6.9 +/- 1.9 microM). Transcription
      of many detoxifying enzymes is regulated through the antioxidant response element
      (ARE) and its transcription factor Nrf2, which is repressed under basal
      conditions by Keap1. However, exposure to electrophilic inducers that alkylate
      Keap1 results in higher concentrations of free Nrf2 and ARE activation. The ARE
      reporter activity was therefore analyzed in HepG2-ARE-C8 cells after incubation
      with lipophilic extracts of A. sinensis or ligustilide for 24 h. Under these
      conditions, both the extract and the ligustilide increased ARE-luciferase
      reporter activity in a dose-dependent manner. Incubation of ligustilide with GSH
      and subsequent LC-MS-MS analysis revealed that ligustilide as well as oxidized
      ligustilide species covalently modified GSH. In addition, using MALDI-TOF mass
      spectrometry and LC-MS-MS, it was demonstrated that the lipophilic extracts,
      ligustilide, and monooxygenated ligustilide alkylated important cysteine residues
      in human Keap1 protein, thus activating Nrf2 and transcription of ARE regulated
      genes. These observations suggest that A. sinensis dietary supplements
      standardized to ligustilide have potential as chemopreventive agents through
      induction of detoxification enzymes.

PMID- 18808160
TI  - Controlled rupture of magnetic polyelectrolyte microcapsules for drug delivery.
AB  - In this study, a magnetic-sensitive microcapsule was prepared using Fe 3O
      4/poly(allylamine) (Fe 3O 4/PAH) polyelectrolyte to construct the shell.
      Structural integrity, microstructural evolution, and corresponding release
      behaviors of fluorescence dyes and doxorubicin were systematically investigated.
      Experimental observations showed that the presence of the magnetic nanoparticles
      in the shell structure allowed the shell structure to evolve from nanocavity
      development to final rupture of the shell under a given magnetic stimulus of
      different time durations. Such a microstructural evolution of the magnetic
      sensitive shell structure explained a corresponding variation of the drug release
      profile, from relatively slow release to burst-like behavior at different stages
      of stimulus. It has proposed that the presence of magnetic nanoparticles produced
      heat, due to magnetic energy dissipation (as Brown and Neel relaxations), and
      mechanical vibration and motion that induced stress development in the thin
      shell. Both mechanisms significantly accelerated the relaxation of the shell
      structure, causing such a microstructural evolution. With such a controllable
      microstructural evolution of the magnetic-sensitive shell structure, active
      substances can be well-regulated in a manageable manner with a designable profile
      according to the time duration under magnetic field. A cell culture study also
      indicated that the magnetic-sensitive microcapsules allowed a rapid uptake by the
      A549 cell line, a cancerous cell line, suggesting that the magnetic-sensitive
      microcapsule with controllable rupturing behavior of the shell offers a potential
      and effective drug carrier for anticancer applications.

PMID- 18808161
TI  - Estimating kinetic and thermodynamic parameters from single molecule enzyme
      inhibitor interactions.
AB  - We report the application of recently developed microscopic models to estimate
      the apparent kinetic and thermodynamic parameters in a single molecule force
      spectroscopy study of the carbonic anhydrase enzyme and a complementary
      sulfonamide inhibitor. The most probable rupture force for the enzyme-inhibitor
      interaction shows a nonlinear dependency on the log-loading rate. Estimates for
      the kinetic and thermodynamic parameters were obtained by fitting the nonlinear
      dependency to linear cubic potential and cusp potential models and compared to
      the standard Bell-Evans model. The reliability of the estimated parameters was
      verified by modeling the experimental rupture force distributions by the
      theoretically predicted distributions at rupture. We also report that linkers
      that are attached to the enzyme and inhibitor show appreciable effects on the
      apparent kinetic and thermodynamic parameters.

PMID- 18808162
TI  - Eigen kinetics in surface complexation of aqueous metal ions.
AB  - The mechanism of chemisorption of aqueous metal ions at surfaces has long been a
      topical issue in such fields as soil chemistry and bioenvironmental science. Here
      it is quantitatively demonstrated for the first time that release of water from
      the inner hydration shell is the rate-limiting step in inner-sphere surface
      complexation. The reactive intermediate is an outer-sphere complex between metal
      ion and surface site, with an electrostatically controlled stability defined by
      Boltzmann statistics. Using tabulated dehydration rate constants for metal ions,
      the resulting scheme allows for prediction of rates of sorption of aqueous metal
      ions at any type of complexing surface.

PMID- 18808163
TI  - Particle and substrate charge effects on colloidal self-assembly in a sessile
      drop.
AB  - By direct video monitoring of dynamic colloidal self-assembly during solvent
      evaporation in a sessile drop, we investigated the effect of surface charge on
      the ordering of colloidal spheres. The in situ observations revealed that the
      interaction between charged colloidal spheres and substrates affects the mobility
      of colloidal spheres during convective self-assembly, playing an important role
      in the colloidal crystal growth process. Both ordered and disordered growth was
      observed depending on different chemical conditions mediated by surface charge
      and surfactant additions to the sessile drop system. These different self
      assembly behaviors were explained by the Coulombic and hydrophobic interactions
      between surface-charged colloidal spheres and substrates.

PMID- 18808164
TI  - Dispersion and functionalization of nonaqueous synthesized zirconia nanocrystals
      via attachment of silane coupling agents.
AB  - Zirconia (ZrO 2) nanocrystals, synthesized from zirconium(IV) isopropoxide
      isopropanol complex and benzyl alcohol, were dispersed and functionalized in
      organic solvents using three kinds of bifunctional silane coupling agents (SCAs),
      3-glycidoxypropyltrimethoxysilane (GPTMS), 3-aminopropyltriethoxysilane (APTES),
      and 3-isocyanatopropyltriethoxysilane (IPTES). Completely transparent ZrO 2
      dispersions were achieved in tetrahydrofuran (THF) with all three SCAs, in
      pyridine and toluene with APTES and IPTES, and in N, N-dimethylformamide with
      IPTES. Dynamic laser scattering (DLS) measurements and high-resolution
      transmission electron microscopical (HRTEM) observation indicated that the ZrO 2
      nanocrystals are dispersed on a primary particle size level. Fourier transform
      infrared spectroscopy, solid-state (13)C- and (29)Si NMR spectroscopy, and
      thermogravimetric analysis demonstrated that all three SCAs are chemically
      attached to the surface of the ZrO 2 nanoparticles, however, in different bonding
      modes. Except for GPTMS/ZrO 2/THF dispersion and IPTES/ZrO 2/pyridine dispersion,
      all other transparent dispersions have poor long-term stability. The increasing
      polarity, due to high amount of APTES attached and high hydrolysis and
      condensation degree of the bonded APTES, and the aggregation, due to
      interparticle coupling via the bonded triethoxysilyl group, are the causes of the
      poor long-term stability for the ZrO 2 dispersions with APTES and IPTES,
      respectively. Nevertheless, the APTES-functionalized ZrO 2 precipitates can be
      deagglomerated in water to get a stable and transparent aqueous ZrO 2 dispersion
      via addition of a little hydrochloric acid.

PMID- 18808165
TI  - Metallic cation induced one-dimensional assembly of poly(acrylic acid)-1
      dodecanethiol-stabilized gold nanoparticles.
AB  - In this work, we report a simple approach for controllable synthesis of one
      dimensional (1D) gold nanoparticle (AuNP) assemblies in solution. In the presence
      of divalent metallic ions, poly(acrylic acid)-1-dodecanethiol-stabilized AuNPs
      (PAA-DDT@AuNPs) are found to form 1D assemblies in aqueous solution by an ion
      templated chelation process; this causes an easily measurable change in the
      absorption spectrum of the particles. The assemblies are very stable and remain
      suspended in solution for more than one month without significant aggregation.
      The morphologies of these 1D assemblies are dependent on the concentration of
      metallic cations in the solution. While lower concentrations led to the formation
      of particle dimers, higher concentrations generated long nanoparticle chain
      networks. In addition, the effect of EDTA, the solution pH, and the size of the
      PAA-DDT@AuNPs is also studied for further exploration of the mechanism of the
      formation of the 1D assemblies.

PMID- 18808166
TI  - Dynamic forces between bubbles and surfaces and hydrodynamic boundary conditions.
AB  - A bubble attached to the end of an atomic force microscope cantilever and driven
      toward or away from a flat mica surface across an aqueous film is used to
      characterize the dynamic force that arises from hydrodynamic drainage and
      electrical double layer interactions across the nanometer thick intervening
      aqueous film. The hydrodynamic response of the air/water interface can range from
      a classical fully immobile, no-slip surface in the presence of added surfactants
      to a partially mobile interface in an electrolyte solution without added
      surfactants. A model that includes the convection and diffusion of trace surface
      contaminants can account for the observed behavior presented. This model predicts
      quantitatively different interfacial dynamics to the Navier slip model that can
      also be used to fit dynamic force data with a post hoc choice of a slip length.

PMID- 18808167
TI  - Dielectric response of a concentrated colloidal suspension in a salt-free medium.
AB  - In this paper the complex dielectric constant of a concentrated colloidal
      suspension in a salt-free medium is theoretically evaluated using a cell model
      approximation. To our knowledge this is the first cell model in the literature
      addressing the dielectric response of a salt-free concentrated suspension. For
      this reason, we extensively study the influence of all the parameters relevant
      for such a dielectric response: the particle surface charge, radius, and volume
      fraction, the counterion properties, and the frequency of the applied electric
      field (subgigahertz range). Our results display the so-called counterion
      condensation effect for high particle charge, previously described in the
      literature for the electrophoretic mobility, and also the relaxation processes
      occurring in a wide frequency range and their consequences on the complex
      electric dipole moment induced on the particles by the oscillating electric
      field. As we already pointed out in a recent paper regarding the dynamic
      electrophoretic mobility of a colloidal particle in a salt-free concentrated
      suspension, the competition between these relaxation processes is decisive for
      the dielectric response throughout the frequency range of interest. Finally, we
      examine the dielectric response of highly charged particles in more depth,
      because some singular electrokinetic behaviors of salt-free suspensions have been
      reported for such cases that have not been predicted for salt-containing
      suspensions.

PMID- 18808168
TI  - Design, synthesis, and biological evaluation of an antagonist-bombesin analogue
      as targeting vector.
AB  - The gastrin releasing peptide receptor (GRP-R) is overexpressed on a number of
      tumors and cancer cell lines including pancreas, prostate, breast,
      gastrointestinal, and small cell lung cancer (SCLC). Radiolabeled bombesin (BBN)
      analogues have exhibited high binding affinity and specificity to the GRP-R. A
      bombesin analogue with an antagonist targeting vector at the C-terminus, DOTA
      aminohexanoyl-[D-Phe(6), Leu-NHCH 2CH 2CH3(13), des Met(14)] BBN[6-14] (1,
      "Bomproamide"), has been synthesized and displays high binding affinity (IC50 =
      1.36 +/- 0.09 nM) against (125)I-Tyr (4)-BBN in in vitro competitive assays using
      PC-3 cells. Maximum internalization of (111)In-1 reached 14% in PC-3 cells after
      45 min of incubation. Rapid (0.25 h PI) and high (12.21 +/- 3.2%ID/g) pancreatic
      uptake of (111)In-1 was observed in healthy CF-1 mice, and 90% of the activity
      was blocked by coinjection of 100 mug of BBN. Rapid (0.25 h PI) and high uptake
      (6.90 +/- 1.06%ID/g) was observed in PC-3 prostate cancer xenografts in SCID
      mice, as well as visualized clearly in a SPECT/CT study. These results support
      the use of a bombesin construct with an antagonist C-terminal vector as a
      candidate of choice for specific in vivo imaging of tumors overexpressing GRP
      receptors.

PMID- 18808169
TI  - Modularly assembled magnetite nanoparticles enhance in vivo targeting for
      magnetic resonance cancer imaging.
AB  - Modularly assembled targeting nanoparticles were synthesized through self
      assembly of targeting moieties on surfaces of functional nanoparticles. Specific
      molecular recognition of nickel nitrilotriacetate on Fe3O4 nanoparticles with
      hexahistidine tag on RGD4C peptides results in precisely controlled orientation
      of the targeting peptides. Better selectivity of the self-assembled RGD4C-Fe3O4
      nanoparticles targeting oral cancer cells than that achievable through a
      conventional chemical cross-link strategy was demonstrated by means of atomic
      absorption spectrometry (AAS). An oral cancer hamster model was applied to reveal
      specific in vivo targeting and MR molecular imaging contrast in cancer lesions
      expressing alphavbeta3 integrin. Both AAS and MRI revealed that the self
      assembled nanoparticles improved the targeting efficiency and reduced the hepatic
      uptake as compared with the conventional chemical cross-link particles. We
      investigated the biosafety, biodistribution, and kinetics of the nanoparticles
      and found that the nanoparticles were significantly cleared from the liver and
      kidneys after one week. By recombining the desired targeting moiety and various
      functional nanoparticles through self-assembly, this new modularly designed
      platform has the capability of enhancing the efficiency of targeted diagnosis and
      therapies for a wide spectrum of biomedical applications.

PMID- 18808170
TI  - The inhibitory potencies of monoclonal antibodies to the macrophage adhesion
      molecule sialoadhesin are greatly increased following PEGylation.
AB  - PEGylation of antibodies is known to increase their half-life in systemic
      circulation, but nothing is known regarding whether PEGylation can improve the
      inhibitory potency of antibodies against target receptors. In this paper, we have
      examined this question using antibodies directed to Sialoadhesin (Sn), a
      macrophage-restricted adhesion molecule that mediates sialic acid dependent
      binding to different cells. Anti-Sn monoclonal antibodies (mAbs), SER-4 and 3D6,
      were conjugated to PEG 5 kDa or and PEG 20 kDa, resulting in the incorporation of
      up to 3 molecules of PEG per mAb molecule. Following purification of PEGylated
      mAbs by anion exchange chromatography, it was shown that PEGylation had little or
      no effect on antigen binding activity but led to a dramatic increase in
      inhibitory potency that was proportional to both the size of the PEG and the
      degree of derivatization. Thus, PEGylation of antibodies directed to cell surface
      receptors could be a powerful approach to improve the therapeutic efficacy of
      antibodies, not only by increasing their half-life in vivo, but also by
      increasing their inhibitory potency for blocking receptor-ligand interactions.

PMID- 18808171
TI  - Lamin A Ser404 is a nuclear target of Akt phosphorylation in C2C12 cells.
AB  - Akt/PKB is a central activator of multiple signaling pathways coupled with a
      large number of stimuli. Although both localization and activity of Akt in the
      nuclear compartment are well-documented, most Akt substrates identified so far
      are located in the cytoplasm, while nuclear substrates have remained elusive. A
      proteomic-based search for nuclear substrates of Akt was undertaken, exploiting
      2D-electrophoresis/MS in combination with an anti-Akt phosphosubstrate antibody.
      This analysis indicated lamin A/C as a putative substrate of Akt in C2C12 cells.
      In vitro phosphorylation of endogenous lamin A/C by recombinant Akt further
      validated this result. Moreover, by phosphopeptide analysis and point mutation,
      we established that lamin A/C is phosphorylated by Akt at Ser404, in an
      evolutionary conserved Akt motif. To delve deeper into this, we raised an
      antibody against the lamin A Ser404 phosphopeptide which allowed us to determine
      that phosphorylation of lamin A Ser404 is triggered by the well-known Akt
      activator insulin, and is therefore to be regarded as a physiological response.
      Remarkably, expression of S404A lamin A in primary cells from healthy tissue
      caused the nuclear abnormalities that are a hallmark of Emery-Dreifuss muscular
      dystrophy (EDMD) cells. Indeed, it is known that mutations at several sites in
      lamin A/C cause autosomal dominant EDMD. Very importantly, we show here that Akt
      failed to phosphorylate lamin A/C in primary cells from an EDMD-2 patient with
      lamin A/C mutated in the Akt consensus motif. Together, our data demonstrate that
      lamin A/C is a novel signaling target of Akt, and implicate Akt phosphorylation
      of lamin A/C in the correct function of the nuclear lamina.

PMID- 18808172
TI  - Studying protein phosphorylation in low MW CSF fractions with capLC-ICPMS and
      nanoLC-CHIP-ITMS for identification of phosphoproteins.
AB  - An initial study of protein phosphorylation in human cerebral spinal fluid (CSF)
      is described. CSF is an important body fluid for study of proteins and
      metabolites and may lead to the ultimate development of molecular markers to
      predict neurological diseases or their complications, such as in the case of
      hemorrhagic stroke. The use of capillary liquid chromatography coupled to
      inductively coupled plasma mass spectrometry (capLC-ICPMS) for screening using
      (31)P as the internal elemental tag atom at ultratrace levels, in combination
      with molecular mass spectrometry using Spectrum Mill and MASCOT database search
      engines for peptide identification, is a novel approach in its application to CSF
      relevant phosphopeptides and phosphorylated proteins. CapLC-ICPMS combined with
      nano liquid chromatography electrospray ionization, ion trap mass spectrometry
      (nanoLC-CHIP/ITMS), was utilized for initial experiments with CSF. Specific low
      level screening for (31)P containing compounds is accomplished, and nanoLC
      CHIP/ITMS provided the corresponding peptide information and subsequent protein
      identifications. The fractions containing (31)P from screening by the capLC-ICPMS
      were collected offline and analyzed separately with nanoLC-CHIP/ITMS. Synthetic
      phosphopeptides were used to test the method and to estimate lowest quantifiable
      limits for phosphorus. Tryptically digested beta-casein was then used to
      demonstrate the viability of the methodology for the complex CSF matrix from
      hemorrhagic stroke patients while also analyzing for native phosphopeptides in
      the CSF.

PMID- 18808173
TI  - Genome-based analysis of heme biosynthesis and uptake in prokaryotic systems.
AB  - Heme is the prosthetic group of many proteins that carry out a variety of key
      biological functions. In addition, for many pathogenic organisms, heme (acquired
      from the host) may constitute a very important source of iron. Organisms can meet
      their heme demands by taking it up from external sources, by producing the
      cofactor through a dedicated biosynthetic pathway, or both. Here we analyzed the
      distribution of proteins specifically involved in the processes of heme
      biosynthesis and heme uptake in 474 prokaryotic organisms. These data allowed us
      to identify which organisms are capable of performing none, one, or both
      processes, based on the similarity to known systems. Some specific instances
      where one or more proteins along the pathways had unusual modifications were
      singled out. For two key protein domains involved in heme uptake, we could build
      a series of structural models, which suggested possible alternative modes of heme
      binding. Future directions for experimental work are given.

PMID- 18808174
TI  - The proteomic response of Saccharomyces cerevisiae in very high glucose
      conditions with amino acid supplementation.
AB  - Ethanol yield by Saccharomyces cerevisiae in very high glucose (VHG) media with
      an amino acid supplement was investigated. Amino acid supplementation led to
      positive cell responses, including reduced lag time and increased cell viability
      in VHG media. A quantitative shotgun proteomic analysis was used to understand
      how amino acid supplemented S. cerevisiae responds to high osmotic conditions.
      iTRAQ data revealed that most proteins involved in glycolysis and pentose
      phosphate pathways were up-regulated under high glucose shock. Reactivation of
      amino acid metabolism was also observed at the end of the lag phase. The relative
      abundance of most identified proteins, including aminoacyl-tRNA biosynthesis
      proteins, and heat-shock proteins, remained unchanged in the hours immediately
      following application of glucose shock. However, the expression of these proteins
      increased significantly at the end of the lag phase. Furthermore, the up
      regulation of trehalose and glycogen biosynthesis proteins, first maintaining
      then latterly increasing glycolysis pathway activity was also observed. This was
      verified by enhanced ethanol yields at 10 and 12 h (0.43 and 0.45 g ethanol/g
      glucose) compared to 2 h (0.32 g ethanol/g glucose). These data combined with
      relevant metabolite measurements demonstrates that enhanced ethanol fermentation
      under VHG conditions can be achieved with the aid of amino acid supplementation.

PMID- 18808175
TI  - Differential proteome expression associated with urokinase plasminogen activator
      receptor (uPAR) suppression in malignant epithelial cancer.
AB  - Dysregulation of the plasminogen activation cascade is a prototypic feature in
      many malignant epithelial cancers. Principally, this is thought to occur through
      activation of overexpressed urokinase plasminogen activator (uPA) concomitant
      with binding to its high specificity cell surface receptor urokinase plasminogen
      activator receptor (uPAR). Up-regulation of uPA and uPAR in cancer appears to
      potentiate the malignant phenotype, either (i) directly by triggering plasmin
      mediated degradation or activation of uPA's or plasmin's proteolytic targets
      (e.g., extracellular matrix zymogen proteases or nascent growth factors) or
      indirectly by simultaneously altering a range of downstream functions including
      signal transduction pathways ( Romer, J. ; Nielsen, B. S. ; Ploug, M. The
      urokinase receptor as a potential target in cancer therapy Curr. Pharm. Des.
      2004, 10 ( 19), 235976 ). Because many malignant epithelial cancers express high
      levels of uPAR, uPA or other components of the plasminogen activation cascade and
      because these are often associated with poor prognosis, characterizing how uPAR
      changes the downstream cellular "proteome" is fundamental to understanding any
      role in cancer. This study describes a carefully designed proteomic study of the
      effects of antisense uPAR suppression in a previously studied colon cancer cell
      line (HCT116). The study utilized replicate 2DE gels and two independent gel
      image analysis software packages to confidently identify 64 proteins whose
      expression levels changed (by > or =2 fold) coincident with a moderate (
      approximately 40%) suppression of cell-surface uPAR. Not surprisingly, many of
      the altered proteins have previously been implicated in the regulation of tumor
      progression (e.g., p53 tumor suppressor protein and c-myc oncogene protein among
      many others). In addition, through a combination of proteomics and immunological
      methods, this study demonstrates that stathmin 1alpha, a cytoskeletal protein
      implicated in tumor progression, undergoes a basic isoelectric point shift (p I)
      following uPAR suppression, suggesting that post-translational modification of
      stathmin occur secondary to uPAR suppression. Overall, these results shed new
      light on the molecular mechanisms involved in uPAR signaling and how it may
      promulgate the malignant phenotype.

PMID- 18808176
TI  - Influence of concentration and anion size on hydration of H+ ions and water
      structure.
AB  - Neutron diffraction experiments with hydrogen isotope substitution on aqueous
      solutions of HCl and HBr have been performed at concentrations ranging from 1:17
      to 1:83 solute per water molecules, at ambient conditions. Data are analyzed
      using the empirical potential structure refinement technique in order to extract
      information on both the ion hydration shells and the microscopic structure of the
      solvent. It is found that the influence of these solutes on the water structure
      is less concentration dependent than that of salts or hydroxides. Moreover
      protons readily form a strong H-bond with a water molecule upon solvation, at all
      proportions. The majority of them is also bonded via a longer bond to another
      water molecule, giving a prepeak in the g(OwOw). At high solute concentration,
      the second water molecule may be substituted by the counterion. In particular at
      solute concentrations of the order of 1:17 or higher, all protons have an anion
      within a distance of 4.5 A.

PMID- 18808177
TI  - Shear deformation and division of cylindrical walls in free-standing nematic
      films under high electric fields.
AB  - We report on the behavior of cylindrical walls formed in a substrate-free nematic
      film of PCH5 under the action of an in-plane ac field. In the film, with vertical
      molecular alignment at all the limiting surfaces, annular Brochard-Leger walls
      are induced well above the bend-Freedericksz threshold. They exhibit, at high
      field strengths, a new type of instability not encountered in sandwich, or any
      other, cell configuration. It manifests as a shearing of the loop-wall between
      the opposite free-surfaces. The shear strain is measured as a function of time,
      field strength, frequency, and temperature. Significantly, the strain is linear
      in field strength. The origin of shear and its dependence on field variables are
      explained through an adaptation of the Carr-Helfrich mechanism of charge
      separation. The sheared wall is stable against pincement up to several times the
      threshold field, and divides itself into two fragments under a large enough
      strain. With the shear distortion, linear defects appear in the opposite splay
      bend regions, just as Neel lines in Bloch walls of magnetic systems. At very low
      frequencies, flexoelectric influence on distortion is revealed.

PMID- 18808178
TI  - A new similarity found from the correspondence of the critical and Zeno-line
      parameters.
AB  - We find a new similarity based on the relation between the critical and unit
      compressibility line (Zeno-line) parameters. Our study relies on the fact that
      the Zeno-line must be tangential to the extension of the binodal liquid branch at
      the zero temperature domain. We show that this similarity faithfully describes
      both the numerical simulation data and experimental data for a wide class of real
      materials (17 gases, water, and 5 metals). Finally we make some predictions for
      metals which have critical parameters in the phase diagram domain still
      inaccessible for experiment.

PMID- 18808179
TI  - Anisotropic molecular structure in dip-coated films of linear poly(ethylene
      imine) studied by infrared multiple-angle incidence resolution spectrometry.
AB  - Molecular structure in dip-coated films of linear poly(ethylene imine) (LPEI) on
      a germanium (Ge) substrate in dried and hydrated conditions have been analyzed by
      infrared multiple-angle incidence resolution spectrometry (IR MAIRS). The MAIRS
      IP (in-plane) and -OP (out-of-plane) spectra of the dried film exhibited largely
      different patterns from each other, which indicated that LPEI molecules had an
      apparent molecular orientation with respect to the substrate surface. Although
      the film exhibited no peak in X-ray diffraction patterns, the low-crystallinity
      film has been found to have highly oriented molecular structure. Many key bands
      indicated that the molecules were involved in the double-stranded helix
      structure, which is specific to the anhydrate crystal of LPEI, with nearly
      perpendicular orientation. The Davydov splitting of the NH stretching vibration
      mode was readily captured by the IR MAIRS spectra, which also supported the helix
      standing model. When the film was stored in a humid condition, on the other hand,
      IR MAIRS spectra revealed that the helix was resolved to be straight chains, but
      the perpendicular orientation was kept unchanged. In addition, the MAIRS spectra
      also revealed molecular orientation of the water molecules of crystallization.
      The unique molecular arrangements are understandable by considering that the
      stabilization energy in the polymer monolayer directly attached on the substrate
      surface is minimized by the standing-molecule arrangements.

PMID- 18808180
TI  - Functionalization of multiwalled carbon nanotubes by pyrene-labeled hydroxypropyl
      cellulose.
AB  - Pyrene-labeled hydroxypropyl cellulose (HPC-Py) was synthesized through a
      condensation reaction between hydroxypropyl cellulose (HPC) and 1-pyrenebutyric
      acid (Py). A hybrid (HPC/MWNTs) of the HPC-Py and multiwalled carbon nanotubes
      (MWNTs) was prepared through a noncovalent method. Temperature-variable UV-vis
      spectra indicated that the HPC-Py had a lower critical solution temperature of
      about 44 degrees C in water. (1)H NMR, UV-vis, Raman, and fluorescence spectra
      were used to systematically investigate the pi-pi stacking interaction between
      the HPC-Py and MWNTs. Dispersion experiments showed the HPC/MWNTs hybrids could
      be well dispersed in water and many organic solvents.

PMID- 18808181
TI  - Structure and molecular mobility of soy glycinin in the solid state.
AB  - We report a multitechnique study of structural organization and molecular
      mobility for soy glycinin at a low moisture content (<30% w/w) and relate these
      to its glass-to-rubber transition. Small-angle X-ray scattering (SAXS),
      differential scanning calorimetry (DSC), Fourier transform infrared (FTIR)
      spectroscopy, and nuclear magnetic resonance (NMR) spectroscopy are used to probe
      structure and mobility on different length and time scales. NMR (approximately
      10(-6) to 10(-3) s) reveals transitions at a higher moisture content (>17%) than
      DSC or SAXS, which sample for much longer times (approximately 10 to 10(3) s) and
      where changes are detected at >13% water content at 20 degrees C. The mobility
      transitions are accompanied by small changes in unit-cell parameters and IR band
      intensities and are associated with the enhanced motion of the polypeptide
      backbone. This study shows how characteristic features of the ordered regions of
      the protein (probed by SAXS and FTIR) and mobile segments (probed by NMR and DSC)
      can be separately monitored and integrated within a mobility transformation
      framework.

PMID- 18808182
TI  - Cycloartane glycosides from Sutherlandia frutescens.
AB  - Four new cycloartane glycosides, sutherlandiosides A-D (1-4), were isolated from
      the South African folk medicine Sutherlandia frutescens and their structures
      established by spectroscopic methods and X-ray crystallography as 1 S,3 R,24S,25
      tetrahydroxy-7S,10S-epoxy-9,10- seco-9,19-cyclolanost-9(11)-ene 25-O-beta-D
      glucopyranoside (1), 3R,7S,24S,25-tetrahydroxycycloartan-1-one 25-O-beta-D
      glucopyranoside (2), 3R,24S,25-trihydroxycycloartane-1,11-dione 25-O-beta-D
      glucopyranoside (3), and 7S,24S,25-trihydroxycycloart-2-en-1-one 25-O-beta-D
      glucoyranoside (4). Compound 1 represents the first secocycloartane skeleton
      possessing a 7,10-oxygen bridge. Compounds 2- 4 are also the first examples of
      naturally occurring cycloartanes with a C-1 ketone functionality. Biosynthetic
      considerations and chemical evidence suggest that the presence of the C-1 ketone
      in 2 may facilitate the ring opening of the strained cyclopropane system.

PMID- 18808183
TI  - Nucleophilic fluorination of triflates by tetrabutylammonium bifluoride.
AB  - Careful examination of nucleophilicity, basicity, and leaving group ability led
      us to discover the nucleophilic fluorination of triflates by weakly basic
      tetrabutylammonium bifluoride, which provides excellent yields with minimal
      formation of elimination-derived side products. Primary hydroxyl groups as well
      as secondary hydroxyl groups in acyclic chains or in five-membered rings are
      excellent substrates, whereas benzylic and aldol-type secondary hydroxyl groups
      give poor yields as a result of the instability of their triflates.

PMID- 18808184
TI  - Suzuki cross-coupling/reductive debenzyloxycarbonylation sequence for the
      syntheses of [c]annulated isoquinolines: application for the syntheses of
      pancratistatin-like isoquinolines.
AB  - A two-step strategy involving Suzuki cross-coupling of boronic acids with a
      diverse array of alpha-iodoenones followed by hydrogenation is developed for the
      construction of [c]annulated isoquinolines. This mild and efficient procedure is
      also applied to the synthesis of highly oxygenated isoquinolines.

PMID- 18808185
TI  - Rapid synthesis of 1,3,4,4-tetrasubstituted beta-lactams from methyleneaziridines
      using a four-component reaction.
AB  - 2-Methyleneaziridines can be transformed into a variety of 1,3,4,4
      tetrasubstituted beta-lactams in moderate to good yields (46-63%) via a "one-pot"
      process that brings together four components with the formation of three new
      intermolecular carbon-carbon bonds.

PMID- 18808186
TI  - Traceless chiral auxiliaries for the allene ether Nazarov cyclization.
AB  - The key stereochemical factors that determine transfer of asymmetry from the
      chiral auxiliary to the cyclopentenone in the allene ether version of the Nazarov
      reaction have been elucidated. On the basis of the new insights into the
      mechanism, two highly effective chiral auxiliaries were designed and prepared.

PMID- 18808187
TI  - Installation of electron-donating protective groups, a strategy for glycosylating
      unreactive thioglycosyl acceptors using the preactivation-based glycosylation
      method.
AB  - Preactivation-based chemoselective glycosylation is a powerful strategy for
      oligosaccharide synthesis with its successful application in assemblies of many
      complex oligosaccharides. However, difficulties were encountered in reactions
      where glycosyl donors bearing multiple electron-withdrawing groups failed to
      glycosylate hindered unreactive acceptors. In order to overcome this problem, it
      was discovered that the introduction of electron-donating protective groups onto
      the glycosyl donors can considerably enhance their glycosylating power, leading
      to productive glycosylations even with unreactive acceptors. This observation is
      quite general and can be extended to a wide range of glycosylation reactions,
      including one-pot syntheses of chondroitin and heparin trisaccharides. The
      structures of the reactive intermediates formed upon preactivation were
      determined through low-temperature NMR studies. It was found that for a donor
      with multiple electron-withdrawing groups, the glycosyl triflate was formed
      following preactivation, while the dioxalenium ion was the major intermediate
      with a donor bearing electron-donating protective groups. As donors were all
      cleanly preactivated prior to the addition of the acceptors, the observed
      reactivity difference between these donors was not due to selective activation
      encountered in the traditional armed-disarmed strategy. Rather, it was
      rationalized by the inherent internal energy difference between the reactive
      intermediates and associated oxacarbenium ion like transition states during
      nucleophilic attack by the acceptor.

PMID- 18808188
TI  - Microwave-assisted parallel synthesis of fused heterocycles in a novel parallel
      multimode reactor.
AB  - New rotor types using disposable glass vials for small-scale parallel synthesis
      in multimode microwave reactors are introduced. One rotor comprises 16 groups of
      four vials, whereas the second uses four silicon carbide plates with a 6 x 4
      matrix to process the vials. Both rotors achieve utmost temperature homogeneity
      upon microwave irradiation and can be used for microwave-mediated reactions at
      temperatures of up to 200 degrees C and pressures of 20 bar. The generation of
      three different heterocycle libraries furnishing thiophenes, oxindoles, and
      benzimidazoles using the new rotor types is described.

PMID- 18808189
TI  - Dynamic selection of novel vancomycin N-terminal derivatives by resin-bound
      reversed D-Ala-D-Ala.
AB  - The most attractive advantage of dynamic combinatorial chemistry (DCC) is that it
      can screen the compound library as soon as compounds are synthesized. However, it
      is very difficult to analyze a dynamic combinatorial library with free probes
      using the state-of-the art analysis technologies. We report herein a method that
      uses a resin-immobilizing reversed peptide probe to screen vancomycin derivatives
      and provides a solution to this problem.

PMID- 18808190
TI  - Cotunneling model for current-induced events in molecular wires.
AB  - Many phenomena in molecular transport junctions involve transitions between
      electronic states of the molecular wire, and, therefore, cannot be described
      adequately using the Landauer picture. We present a model for cotunneling
      processes in molecular wires. These are coherent second-order processes that can
      be observed at low temperatures. As an example, we consider the STM-induced
      dissociation of acetylene. The large voltage threshold for dissociation observed
      experimentally is naturally accounted for within the cotunneling model.

PMID- 18808191
TI  - Vertically aligned nanowires from boron-doped diamond.
AB  - Vertically aligned diamond nanowires with controlled geometrical properties like
      length and distance between wires were fabricated by use of nanodiamond particles
      as a hard mask and by use of reactive ion etching. The surface structure,
      electronic properties, and electrochemical functionalization of diamond nanowires
      were characterized by atomic force microscopy (AFM) and scanning tunneling
      microscopy (STM) as well as electrochemical techniques. AFM and STM experiments
      show that diamond nanowire etched for 10 s have wire-typed structures with 3-10
      nm in length and with typically 11 nm spacing in between. The electrode active
      area of diamond nanowires is enhanced by a factor of 2. The functionalization of
      nanowire tips with nitrophenyl molecules is characterized by STM on clean and on
      nitrophenyl molecule-modified diamond nanowires. Tip-modified diamond nanowires
      are promising with respect to biosensor applications where controlled biomolecule
      bonding is required to improve chemical stability and sensing significantly.

PMID- 18808192
TI  - Acoustic oscillations and elastic moduli of single gold nanorods.
AB  - We present the first acoustic vibration measurements of single gold nanorods with
      well-characterized dimensions and crystal structure. The nanorods have an average
      size of 90 nm x 30 nm and display two vibration modes, the breathing mode and the
      extensional mode. Correlation between the dimensions obtained from electron
      microscope images and the vibrational frequencies of the same particle allows us
      to determine the elastic moduli for each individual nanorod. Contrary to previous
      reports on ensembles of gold nanorods, we find that the single particle elastic
      moduli agree well with bulk values.

PMID- 18808193
TI  - Sequence structure of hidden 10.4-base repeat in the nucleosomes of C. elegans.
AB  - By measuring prevailing distances between YY, YR, RR, and RY dinucleotides in the
      large database of the nucleosome DNA fragments from C. elegans, the consensus
      sequence structure of the nucleosome DNA repeat of C. elegans was reconstructed:
      (YYYYYRRRRR)n. An actual period was estimated to be 10.4 bases. The pattern is
      fully consistent with the nucleosome DNA patterns of other eukaryotes, as
      established earlier, and, thus, the YYYYYRRRRR repeat can be considered as
      consensus nucleosome DNA sequence repeat across eukaryotic species. Similar
      distance analysis for [A, T] dinucleotides suggested the related pattern
      (TTTYTARAAA)n where the TT and AA dinucleotides display rather out of phase
      behavior, contrary to the "AA or TT" in-phase periodicity, considered in some
      publications. A weak 5-base periodicity in the distribution of TA dinucleotides
      was detected.

PMID- 18808195
TI  - Synthesis, characterization, and DNA-binding properties of Ln(III) complexes
      containing gatifloxacin.
AB  - Four novel water-soluble complexes of Ln(III) with gatifloxacin (HGA),
      [La(HGA)3Cl3] x 2H2O, [Nd(HGA)3Cl3] x 2H2O, [Eu(HGA)3Cl3] x 2H2O, [Tb(HGA)3Cl3] x
      2H2O, have been synthesized and characterized by elemental analyses, molar
      conductivities, IR spectra, fluorescence spectra, and
      thermogravimetry/differential thermal analysis (TG-DTA). In addition, the DNA
      binding properties of the ligand and its complexes have been investigated by
      absorption, fluorescence spectra, and viscosity measurements. The experimental
      results indicated that the complexes and ligand bind to DNA via groove binding
      mode.

PMID- 18808194
TI  - A computational study of expanded heterocyclic nucleosides in DNA.
AB  - The first molecular dynamics study of a series of heterospacer-expanded tricyclic
      bases in DNA using modified force field parameters in AMBER is detailed. The
      expanded purine nucleoside monomers have been designed to probe the effects of a
      heteroaromatic spacer ring on the structure, function, and dynamics of the DNA
      helix. The heterobase scaffold has been expanded with a furan, pyrrole, or
      thiophene spacer ring. This structural modification increases the polarizability
      of the bases and provides an additional hydrogen bond donor with the amine
      hydrogen of the pyrrole ring or hydrogen bond acceptor with the furan or
      thiophene ring free electron pairs. The polarizability of the expanded bases were
      determined by AM1 calculations and the results of the MD simulations of 20-mers
      predict that the modified curvature of the expanded base leads to a much larger
      major groove, while the effect on the minor groove is negligible. Overall, the
      structure resembles A-DNA. MD simulations of 10-mers suggest that the balance
      between base pairing vs. base stacking and intercalation can be shifted towards
      the latter due to the increased surface area and polarizability of the expanded
      bases.

PMID- 18808196
TI  - Intramolecular recombination R-triplex in solution: stabilization by bis
      intercalator YOYO.
AB  - Recognition of double-stranded DNA with a mixed nucleotide sequence by
      oligonucleotide is a long-term challenge. This aim can be achieved via formation
      of the recombination R-triplex, accommodating two identical DNA strands in
      parallel orientation, and antiparallel complementary strand. In the absence of
      proteins the R-triplex stability is low, however, so that intermolecular R
      triplex is not formed by three DNA strands in a ligand-free system. Recently,
      recognition of DNA with mixed base sequence by single-stranded oligonucleotide in
      the presence of bis-intercalator YOYO was reported. Here, we describe
      thermodynamic characteristics of YOYO complexes with the model oligonucleotides
      5'-GT-2AP-GACTGAG TTTT CTCAGTCTACGC GAA GCGTAGACTGAG-3' (R(2AP)CW) bearing a
      single reporting 2-aminopurine (2AP) in place of adenine and 5'-CTCAGTCTACGC GAA
      GCGTAGACTGAG-3' (CW). We found that each oligonucleotide is able to bind two YOYO
      molecules via intercalation mode in 0.5 M LiCl. Fluorescence intensity of YOYO
      intercalated in triplex R(2AP)CW and in CW hairpin increased 40-fold compared to
      the free YOYO. Remarkably, the melting temperature of the triplex (determined
      using temperature dependence of the 2AP fluorescence) increased from 19 degrees C
      to 33 degrees C upon binding two YOYO molecules. Further increase in the YOYO
      concentration resulted in binding of up to five YOYO molecules to R(2AP)CW
      triplex and up to six YOYO molecules to CW hairpin.

PMID- 18808197
TI  - DNA-binding and oxidative properties of cationic phthalocyanines and their
      dimeric complexes with anionic phthalocyanines covalently linked to
      oligonucleotides.
AB  - Design of chemically modified oligonucleotides for regulation of gene expression
      has attracted considerable attention over the past decades. One actively pursued
      approach involves antisense or antigene oligonucleotide constructs carrying
      reactive groups, many of these based on transition metal complexes. The complexes
      of Fe(II) and Co(II) with phthalocyanines are extremely good catalysts of
      oxidation of organic compounds with molecular oxygen and hydrogen peroxide. The
      binding of positively charged Fe(II) and Co(II) phthalocyanines with single- and
      double-stranded DNA was investigated. It was shown that these phthalocyanines
      interact with nucleic acids through an outside binding mode. The site-directed
      modification of single-stranded DNA by O2 and H2O2 in the presence of dimeric
      complexes of negatively and positively charged Fe(II) and Co(II) phthalocyanines
      was investigated. These complexes were formed directly on single-stranded DNA
      through interaction between negatively charged phthalocyanine in conjugate and
      positively charged phthalocyanine in solution. The resulting oppositely charged
      phthalocyanine complexes showed significant increase of catalytic activity
      compared with monomeric forms of phthalocyanines Fe(II) and Co(II). These
      complexes catalyzed the DNA oxidation with high efficacy and led to direct DNA
      strand cleavage. It was determined that oxidation of DNA by molecular oxygen
      catalyzed by complex of Fe(II)-phthalocyanines proceeds with higher rate than in
      the case of Co(II)-phthalocyanines but the latter led to a greater extent of
      target DNA modification.

PMID- 18808198
TI  - Nucleotide triplet based molecular phylogeny of class I and class II aminoacyl t
      RNA synthetase in three domain of life process: bacteria, archaea, and eukarya.
AB  - The aminoacyl-tRNA synthetases are one of the major protein components in the
      translation machinery. These essential proteins are found in all forms of life
      and are responsible for charging their cognate tRNAs with the correct amino acid.
      These important enzymes have been the subject of intense scientific inquiry for
      nearly half a century, but their complete evolutionary history has yet to emerge.
      Amino acids sequence based phylogeny has some limitation due to very low sequence
      similarity amongst the different tRNA synthetases and structure based phylogeny
      has also its limitation. In our study, tRNA nucleotide sequences of E. coli K12
      (Bacteria), Saccharomyces cerevisiae (Eukarya), Thermococcus kodakaraensis KOD1,
      and Archaeoglobus fulgidus DSM 4304 (Archaea) were used for phylogenetic
      analysis. Our results complement the observation with the earlier studies based
      on multiple sequence alignment and structural alignment. We observed that
      relationship between archaeal tRNA synthetases are different that of bacteria and
      eucarya. Violation of Class rule of LysRS is observed here also. The uniqueness
      of this method is that it does not employ sequence alignment of complete
      nucleotide sequence of the corresponding gene.

PMID- 18808199
TI  - Exploring electron transfer between heme proteins of cytochrome C super family in
      biosensors: a molecular mechanics study.
AB  - Electron transfer between heme proteins with mediators plays an important role in
      the fabrication of sensitive bio-nano sensors. Heme protein Cytochrome c (pdb
      code - 1HRC) was chosen as the mediator with Cytochrome c' (pdb code - 1A7V) as
      the probe protein for our investigation on the electron transfer process. We used
      the software GRAMM, HEX, and MACRODOX to build the protein complex with further
      evaluation by GROMACS potential. After molecular mechanics refinement by GROMACS
      the protein complexes were evaluated in terms of the following criteria:
      Hydrophobic packing, proximity of the hemes, hydrogen bonds, enthalpy and entropy
      of binding. The free energy was calculated for each complex to derive the
      feasible stable models. The combined electron transport of the chosen geometric
      models was evaluated to choose the possible models. Electrostatic potential was
      calculated using the program APBS around the heme in the presence and absence of
      other proteins. From our studies, we derived multiple feasible models and
      possible electronic path. These studies helped us to understand the relay
      mechanism between the two proteins and to design mutant proteins by rational site
      directed mutagenesis to enhance the redox potential and thereby improving the
      signal to noise ratio in amperometric bionano sensors.

PMID- 18808200
TI  - Digestion of the lambda cI repressor with various serine proteases and
      correlation with its three dimensional structure.
AB  - Partial proteolysis of the lambda cI repressor has been carried out
      systematically with trypsin, chymotrypsin, elastase, endoproteinase Glu-C,
      kallikrein, and thrombin. The cleavage sites have been determined by (i)
      comparison of fragments produced and observed in SDS-polyacrylamide gel with
      known fragments and plots of distance migrated versus log (molecular weight of
      fragment), (ii) partial Edman sequencing of the stable C-terminal fragments to
      identify cleavage points, and (iii) electrospray mass spectrometry of fragments
      produced. Most cleavage points are found to occur in the region 86-137, saving
      some in the N-terminal domain observed for trypsin and Glu-C. Region 86-137 can
      be further subdivided into three regions 86-91, 114-121, and 128-137 prone to
      cleavage, with intermediate regions resistant to cleavage to all six proteases.
      These resistant regions show that much of the region 93-131 previously called a
      'linker' is actually part of the C-domain as first proposed in all models from
      our laboratory. Region 92-114 includes the cleavage site Ala-Gly, which must be
      buried in the intact repressor. The observed cleavage points in region 114-137
      can be used to judge the best among three previously proposed models since they
      differ from each other in the structure of region 93-131. Model 1j5g is adjudged
      to be better than model 1lwq (which is based on 1kca, a crystal structure) as
      susceptible residues are more exposed in the former and lack of cleavages at six
      sites is better explained. Likewise, the models 1j5g and 1lwq are compared with a
      recent crystal structure of fragment 101-229 in 2ho0 and another low resolution
      crystal structure in 3bdn.

PMID- 18808201
TI  - Dynamics and local ordering of spin-labeled prion protein: an ESR simulation
      study of a highly PH-sensitive site.
AB  - Valine 160 on beta-sheet-2 (S2) of mouse prion (moPrPC) has been previously
      identified as the most highly pH-sensitive site on moPrPC by ESR spectroscopy
      using site-directed spin labeling (SDSL) technique. However, no further
      theoretical analysis to reveal the molecular dynamics reported on the
      experimental ESR spectra is available. The X-band ESR spectra of R1 nitroxide
      spin label at V160 and four other sites are carefully analyzed over large pH and
      temperature ranges using a spectral simulation method based upon stochastic
      Liouville equation (SLE). The results clearly reveal the dynamics and ordering of
      the local environment of V160R1 showing that (i) molecular mobility of V160R1 on
      S2 gradually increases with a decrease of pH from 7.5 to 4.5; (ii) two distinctly
      different spectral components are simultaneously present in all spectra of V160R1
      studied. The spectral components are, respectively, denoted as immobile (Im),
      characterized by lower molecular mobility and higher ordering, and mobile (Mb)
      component of high mobility and low ordering. The population ratio (Im/Mb)
      increases with increasing pH, while Im remains dominant in all V160R1 spectra. It
      suggests a more mobile and disordered dynamic molecular structure for mouse PrPC,
      which is very likely correlated with increased beta-sheet content at low pH, as
      the environment changes from neutral to acidic pH. Together with the results of
      the SLE-based analyses on the spectra of other sites that appear pH-insensitive,
      we suggest that the simultaneous presence of the spectral components for V160R1
      is strongly correlated with the coexistence of multiple protein conformations in
      local structure of PrPC over the varied pH range. It demonstrates that the
      combined approach of the SDSL technique and the SLE-based analysis leads to a
      powerful method for unraveling the complexity of protein dynamics.

PMID- 18808202
TI  - A new method to analyze the similarity of protein structure using TOPS
      representations.
AB  - As a coarse level description of protein structure, TOPS (Topology of protein
      structure) diagrams are simplified descriptions of structural topology of
      proteins and comprise graphical representations of SSEs. In this paper, we
      propose a new method to analyze the similarities/dissimilarities of protein
      structure of TOPS representations based on the graphical representation proposed
      by C. X. Yuan et al. (2003). Instead of calculating the leading eigenvalues of
      the matrix for graphical representation, we compute torsion of curves as the
      descriptor to numerically characterize TOPS strings. Using the new method, TOPS
      strings of the 34 protein chains in the Chew-Kedem data set are analyzed. The
      similarities/ dissimilarities and phylogenetic tree of these protein structures
      verify the validity of our method.

PMID- 18808203
TI  - Molecular modeling and characterization of the B. thuringiensis and B.
      thuringiensis LDC-9 cytolytic proteins.
AB  - The Cyt toxins are able to lyse a wide range of cell types in vitro, unlike the
      Cry delta-endotoxins. It exerts its activity by the formation of pores within
      target cell membranes. The structural information available for Cyt2Aa (PDB id:
      1CBY) consists of a single domain in which two outer layers of alpha-helix wrap
      around a mixed beta-sheet. Beta-barrel was suggested as a possible structure of
      the pores. Hence, this study seeks to investigate the structural properties of
      other Cytolytic proteins by predicting the three-dimensional (3D) model using
      Cyt2Aa as template. The predicted models are expected to be significantly more
      accurate as all the Cyt proteins showed significant similarity with the template
      (PDB id: 1CBY). The refined homology models revealed similar secondary structures
      (alpha-helices and beta-sheets) and tertiary features as Cyt2Aa. The variation in
      the loop regions of the tertiary structure accounts for the differential
      toxicity.

PMID- 18808204
TI  - Modeling of factor XIII activation peptide (28-41) V34L mutant bound to thrombin.
AB  - Factor XIII (FXIII) is a transglutaminase involved in blood coagulation. The
      enzyme is activated by thrombin cleaving the peptide bond R37-G38. A common
      mutation V34L found in FXIII has been correlated with protection from myocardial
      infarction. Also FXIII V34L is activated more quickly than the wild type. In the
      present study, FXIII (28-41) V34L mutant peptide bound to thrombin has been
      modeled and molecular dynamics simulations were carried out using Insight II. An
      average structure was calculated after simulation. The structure showed
      significant difference from the crystal structure of the wild type FXIII (28-37)
      peptide bound to thrombin. In the crystal structure the peptide adopts a folded
      conformation in such a way that the hydrophobic side chains of V29 and V34 occupy
      the apolar binding site of thrombin. The modeled V34L peptide adopts a
      significantly different conformation and only the bulkier L34 occupies the apolar
      binding site while V29 side chain is exposed to the bulk solvent. Hence, this may
      speed up the release of FXIII from thrombin after its activation.

PMID- 18808205
TI  - The effect of histidine residue modification on tyrosinase activity and
      conformation: inhibition kinetics and computational prediction.
AB  - We found that the histidine chemical modification of tyrosinase conspicuously
      inactivated enzyme activity. The substrate reactions with
      diethylpyridinecarbamate showed slow-binding inhibition kinetics (KI = 0.24 +/-
      0.03 mM). Bromoacetate, as another histidine modifier, was also applied in order
      to study inhibition kinetics. The bromoacetate directly induced the exposures of
      hydrophobic surfaces following by complete inactivation via ligand binding. For
      further insights, we predicted the 3D structure of tyrosinase and simulated the
      docking between tyrosinase and diethylpyridinecarbamate. The docking simulation
      was shown to the significant binding energy scores (-3.77 kcal/mol by AutoDock4
      and -25.26 kcal/mol by Dock6). The computational prediction was informative to
      elucidate the role of free histidine residues at the active site, which are
      related to substrate accessibility during tyrosinase catalysis.

PMID- 18808206
TI  - Management of chronic constipation in the elderly.
AB  - Constipation is a significant healthcare problem in the elderly. However, while
      undoubtedly common in the elderly, data on the prevalence of constipation in
      general and of its subtypes vary considerably, depending on the nature of the
      study population and their location. Furthermore, the complexity of the
      pathophysiology of constipation in this age group is little appreciated.
      Assumptions regarding 'age-related changes in colorectal physiology' are, for the
      most part, not supported by scientific evidence and may serve to distract the
      clinician from uncovering the contributions of co-morbid diseases and the impact
      of iatrogenic factors. The evidence base from which one can develop
      recommendations on the management of constipation in the elderly is, for the most
      part, slim. This becomes most starkly apparent when one attempts to critically
      assess specific approaches to management. There is insufficient evidence to
      support the use of many commonly used laxatives both in the general population
      and in the elderly. Lifestyle interventions have value for some patients but data
      are lacking on the benefits of these interventions for patients with chronic
      constipation. Data in the elderly do not exist for most new pharmacological
      approaches to constipation. Pending the availability of good data, management of
      constipation in the elderly should be tailored to each individual's needs and
      expectations, regardless of age or place of residence. In certain situations,
      constipation may be complicated by the development of impaction; preventive
      strategies are important in this context. We urge enrolment of many more elderly
      individuals with chronic constipation in clinical trials designed to address
      their particular needs.

PMID- 18808207
TI  - Viral hepatitis in elderly haemodialysis patients: current prevention and
      management strategies.
AB  - Viral hepatitis continues to be a relevant topic for haemodialysis centres,
      although the number of infected dialysis patients is declining in most countries.
      Chronic hepatitis B and C lead to detrimental complications such as liver
      cirrhosis and hepatocellular carcinoma. These complications can be avoided by
      successful antiviral treatment. In individuals with normal renal function, drug
      therapy of chronic hepatitis B is evolving quickly. Today there are several
      options but no agreed standard therapy. In the absence of renal failure, chronic
      hepatitis C should be treated with a combination of pegylated interferon-alpha
      and ribavirin. For both infections, there is no general indication to treat all
      patients; several criteria can be used to predict benefits and downsides. Chronic
      renal failure severely alters immune function, particularly activation of T
      lymphocytes and cytokine production by mononuclear cells. Aging further
      influences the immune system with deviation of T-lymphocyte differentiation. Both
      effects seem to act additively, leaving the elderly haemodialysis patient with
      extensive immune dysfunction. While these effects do not put the patient at risk
      of opportunistic infection, they do have a relevant effect on the clinical course
      of viral hepatitis. Haemodialysis patients infected with hepatitis B manifest a
      subclinical, often anicteric disease, and at least 60% of the infections become
      chronic. These patients usually do not fulfil the criteria for successful
      antiviral treatment, since they have normal or slightly elevated liver enzyme
      levels and few histological signs of liver inflammation. In addition, the
      prognosis in terms of cirrhosis and hepatocellular carcinoma might be more
      favourable than in individuals with normal renal function. The former standard
      treatment of chronic hepatitis B with interferon-alpha or its derivate pegylated
      interferon was badly tolerated in dialysis patients and associated with low
      efficacy. Indeed, prior to the advent of nucleoside analogues there was a clear
      recommendation not to treat chronic hepatitis B infection in all except a few
      dialysis patients. However, the newer treatment options appear to work well. In
      particular, there is growing evidence for the effectiveness and tolerability of
      lamivudine in dialysis patients, including the elderly. Use of adefovir and
      entecavir has also been reported in a few cases. At present, while we still do
      not recommend treatment, therapy with nucleoside analogues might be an option in
      selected patients, for example, those planning renal transplantation. The major
      effort against hepatitis B should be directed at vaccination and hygienic
      precautions to prevent the infection.Treatment of hepatitis C in patients
      undergoing haemodialysis is also limited by the poor tolerability of interferons.
      Ribavirin is contraindicated because of severe haemolytic anaemia, although a few
      studies have attempted to manage this with administration of high doses of
      erythropoetin. Those patients who complete the full course of interferon therapy
      may expect sustained viral responses comparable with healthy individuals, but in
      most trials, 30-50% of patients were forced to interrupt treatment because of
      adverse effects. There is no general indication to treat chronic hepatitis C in
      haemodialysis patients. Arguments in favour of treatment include elevated liver
      enzymes, histological signs of relevant liver inflammation, younger age, a virus
      genotype other than 1 and planned renal transplantation.

PMID- 18808209
TI  - Acquisition costs and use of Medicare Part D-excluded drugs in Veterans Health
      Administration long-stay nursing home residents: a national, descriptive,
      secondary data analysis.
AB  - BACKGROUND: Nursing home populations may consist of both short- and long-stay
      residents, who have different resource use profiles. Differentiating between
      these two populations is important in any analysis of drug costs and use.
      OBJECTIVE: The aim of this analysis was to provide national annualized estimates
      of drug acquisition costs and use of drugs excluded under Medicare Part D for
      dually eligible long-stay nursing home residents in the US. METHODS: This was a
      national, descriptive, secondary data analysis. The study population consisted of
      6554 Veterans Health Administration (VHA) long-stay nursing home residents (n=136
      nursing homes), identified from the Minimum Data Set (MDS), who had an annual
      assessment during fiscal year (FY) 2005 linked with their 8,847,561 inpatient
      pharmacy claims. The study data generated were descriptive statistics of the
      annual drug acquisition costs and use of medications excluded under Medicare Part
      D. VHA therapeutic drug classes were obtained from FY 2005 national pharmacy
      claims linked at the individual resident level. RESULTS: The excluded drugs
      accounted for 3 036 306 of the more than 8.8 million inpatient pharmacy claims,
      totalling $US3,406,756 or $US526 per resident (99% CI 490, 562). Non-opioid
      analgesics were received by 73.3% of the residents, totalling $US352,608 or $US73
      per resident; 25.3% received antitussives, decongestants, or cold and cough
      medications, totalling $US27,220 or $US16 per resident; 63.8% received vitamins,
      totalling $US281,909 or $US67 per resident; 17.7% received benzodiazepines or
      sedative hypnotics, totalling $US76,083 or $US66 per resident; and 64.3% received
      laxatives or stool softeners, totalling $US298,326 or $US71 per resident. The
      total acquisition cost of all drugs was $US23,782,717 for 6554 VHA nursing home
      residents or $US3629 per resident (99% CI 3343, 3915). CONCLUSION: The cost of
      Medicare Part D-excluded drugs represented a fraction of the total VHA drug costs
      for long-stay nursing home residents, accounting for only 14.3% of all drug costs
      and 34.3% of the more than 8.8 million inpatient pharmacy claims. More research
      is needed to account for the drug dispensing and administration costs associated
      with these excluded classes of drugs and their efficacy. Studies of VHA drug
      acquisition costs provide important policy-relevant data for the Medicare Part D
      national price negotiation debate, particularly in a US presidential election
      year.

PMID- 18808208
TI  - Use of antidepressants in late-life depression.
AB  - Late-life depression (LLD) is a common and typically recurrent illness that is
      often unrecognized and under-treated. It is associated with significant co
      morbidities and poor health outcomes. Antidepressants are typically used as a
      first-line treatment for LLD. We performed a systematic review of the English
      literature (1996 to August 2007) and present results relevant to the efficacy of
      antidepressants in acute and maintenance pharmacotherapy of LLD, the predictors
      of LLD treatment outcomes and pharmacological strategies for non-remission. There
      is a consensus in the literature that the goal of treatment should be remission.
      Although antidepressants can be categorized into several classes based on their
      putative mechanisms of action, there is no consistent evidence that
      antidepressants from different classes are associated with different rates of
      remission of LLD. After achieving remission, the evidence supports a beneficial
      role of maintenance pharmacotherapy in reducing the rate of recurrence of LLD for
      at least 2 years. There are reports of a number of possible augmentation and
      switching strategies that can be used when LLD remission is not attained.
      However, none of these various strategies has been studied rigorously in patients
      with LLD as yet. Overall, the current literature is adequate for guiding acute
      and maintenance pharmacotherapy of LLD but further research is urgently needed to
      guide clinical strategies in non-remission.

PMID- 18808210
TI  - Continuity and adherence to long-term drug treatment by geriatric patients after
      hospital discharge: a prospective cohort study.
AB  - BACKGROUND: Increased life expectancy is associated with an increased prevalence
      of chronic diseases and drug consumption. Changes often occur in the medication
      regimen after hospitalization. The extent and nature of these changes and the
      adherence of elderly patients have not yet been fully investigated. OBJECTIVE: To
      investigate the extent and reasons for modifications to the medication regimens
      of elderly patients and their adherence to treatment during the first month
      following hospital discharge. METHODS: This was a prospective cohort study of 198
      patients aged>or=65 years in the Acute Geriatric Ward, Beilinson Hospital, Rabin
      Medical Center, Israel. Clinical, demographic and medication regimen data were
      recorded for all patients at an interview conducted prior to discharge. After 1
      month, the patient, caregiver or general practitioner (GP) were interviewed
      regarding the extent and reasons for modifications to the medication regimen and
      adherence to treatment. RESULTS: At 1-month post-discharge, on average, 36.7% of
      patient medications had been modified compared with the discharge prescription.
      No modification was found in 16% of patients. During the observation month, 62%
      of prescribed long-term medications were taken without modification as
      recommended at discharge and during follow-up, 50% of all changes were
      characterized by the addition of a drug or an increase in dosage, and 26%, 16%
      and 8% consisted of cancelling, omission or switching within the same medication
      type, respectively. Seventy percent of medication regimen changes were based on
      specialists' recommendations or secondary to a change in the patients' medical
      state, and 13%, 8%, 3% and 6% were as a result of poor adherence, adverse
      effects, administrative restrictions and other reasons, respectively. There was
      no correlation between medication regimen change and age, gender, physical
      function, cognitive function and length of hospital stay. Patients discharged
      home experienced less regimen modification than those discharged elsewhere
      (p=0.02). Patients who visited their GP only once experienced less regimen
      modification (p=0.03). Regression analysis showed that the only factors affecting
      medication regimen changes were GP visits and chronic diseases (p<0.01, R2=0.09).
      The overall mean adherence among 145 home-dwelling patients was 96.7%. Twenty
      seven percent and 6% were under- and over-adherent, respectively, to at least one
      drug; under-adherence was more widespread than over-adherence. No correlation was
      found between the overall mean adherence and other clinical parameters or regimen
      change. However, non-adherence to at least one drug was associated with more
      medication regimen changes (p=0.001), was more common in patients discharged with
      prescriptions for seven or more drug types per day (p=0.01) and was associated
      with failing to visit the patient's GP 1 month after discharge (p=0.02).
      CONCLUSION: The majority of elderly patients experienced modifications in their
      medication regimen during the first month following hospital discharge. Thirty
      percent of patients were non-adherent to at least one drug. To improve adherence
      to a hospital medication regimen, patients should be encouraged to visit their GP
      and the number of long-term drugs should be reduced.

PMID- 18808211
TI  - Concurrent use of anticholinergic drugs and cholinesterase inhibitors: register
      based study of over 700,000 elderly patients.
AB  - BACKGROUND: Although cholinesterase inhibitors are used for the treatment of
      Alzheimer's disease, the clinical benefits of these drugs are being questioned.
      Anticholinergic drugs have the opposite pharmacological action to cholinesterase
      inhibitors, and may antagonize the effects of cholinesterase inhibitors.
      Therefore, this drug combination should be avoided. Nevertheless, high rates of
      concurrent use of anticholinergic drugs and cholinesterase inhibitors have been
      reported in the US. To the authors' knowledge, use of this inappropriate drug
      combination has not been studied outside North America. OBJECTIVE: To investigate
      (i) whether anticholinergic drug use is more common among users than non-users of
      cholinesterase inhibitors, and (ii) which factors are associated with use of
      anticholinergic drugs among users of cholinesterase inhibitors. METHODS: We
      analysed data on age, sex, type of residential area (urban/rural) and drugs
      dispensed for patients aged>or=75 years registered in the Swedish Prescribed Drug
      Register from October to December 2005 (n=731,105). The prevalence of use of
      anticholinergic drugs in users of cholinesterase inhibitors was compared with
      that in non-users of cholinesterase inhibitors and logistic regression was used
      to study the association between use of cholinesterase inhibitors and
      anticholinergic drugs. Logistic regression was also used to analyse whether age,
      sex, type of residential area or number of dispensed drugs was associated with
      use of anticholinergic drugs among users of cholinesterase inhibitors (n=18,326).
      RESULTS: Anticholinergic drug use was more common among cholinesterase inhibitor
      users than non-users, particularly in men, of whom 9% who were taking
      cholinesterase inhibitors were dispensed anticholinergic drugs compared with 5%
      who were not taking cholinesterase inhibitors. Use of cholinesterase inhibitors
      was associated with use of anticholinergic drugs in men (odds ratio 1.23; 95% CI
      1.13, 1.35), after adjustment for age, type of residential area and number of
      dispensed drugs. Male sex and use of many drugs were independently associated
      with concurrent use of anticholinergic drugs and cholinesterase inhibitors.
      CONCLUSION: Anticholinergic drug use is more common among cholinesterase
      inhibitor users than non-users, even though anticholinergic drugs may antagonize
      the effect of cholinesterase inhibitors. Hence, if the true clinical effects of
      cholinesterase inhibitors are to be accurately assessed, they need to be studied
      in the absence of anticholinergic drugs.

PMID- 18808212
TI  - Discontinuation of methotrexate therapy in older patients with newly diagnosed
      rheumatoid arthritis: analysis of administrative health databases in Quebec,
      Canada.
AB  - BACKGROUND: Rheumatoid arthritis (RA) is a potentially devastating form of
      chronic arthritis. Methotrexate is the cornerstone of drug therapy of the
      disorder, and may slow or prevent joint damage. Unfortunately, this agent is not
      without adverse effects. Furthermore, increasing age has been been invoked as a
      predictor of greater toxicity and drug discontinuation by some, but not all,
      investigators. OBJECTIVE: To assess the effect of age and other covariates on
      methotrexate discontinuation in a population-based sample of older patients with
      newly diagnosed RA. METHODS: We studied the health administrative databases
      covering residents of the province of Quebec, Canada. In these databases, we
      identified 246 individuals aged>or=65 years with newly diagnosed RA who had been
      started on methotrexate. We assessed discontinuation of methotrexate therapy
      using Cox proportional hazards regression models, with potential predictors of
      discontinuation being age, sex, co-morbidity, methotrexate dose and route (oral
      vs intramuscular), folic acid coadministration and disease severity. RESULTS:
      Five patients died or were lost to follow-up in the database at 6 months, and
      there were ten such patients at 1 year. Six months after the initial prescription
      of methotrexate therapy, about 80% (n=192) of remaining subjects continued to be
      prescribed the drug. By 1 year, 161 of 236 (68.2%) subjects continued to be
      prescribed the drug; by 2 years, only 108 of 217 (49.8%) subjects continued to
      receive the drug. Increasing age was associated with a greater risk of
      methotrexate discontinuation. CONCLUSION: Our population-based data indicate that
      increasing age is associated with a greater tendency for methotrexate
      discontinuation in patients with newly diagnosed RA. These results emphasize the
      need to ensure that older patients with RA are provided with effective therapy to
      minimize the effects of this chronic, potentially disabling disease.

PMID- 18808213
TI  - Predictors of adherence to concomitant antihypertensive and lipid-lowering
      medications in older adults: a retrospective, cohort study.
AB  - BACKGROUND: Many older individuals have concomitant hypertension and
      dyslipidaemia--two conditions that, together with age, increase the risk of
      adverse cardiovascular events. Adherence to antihypertensive (AH) and lipid
      lowering (LL) therapy is therefore particularly important in older patients with
      concomitant hypertension and dyslipidaemia. OBJECTIVE: To determine patterns and
      predictors of adherence to concomitant AH and LL therapy among an older Medicare
      eligible population. METHODS: Enrolees (n=4052) aged>or=65 years who initiated
      treatment with both AH and LL therapy within a 90-day period were studied in this
      retrospective cohort study conducted in a US managed care organization. Adherence
      to AH and LL medications was measured as the proportion of days covered by any AH
      and/or LL medication in each 3-month interval, from the start of concomitant
      therapy for up to 36 months (mean follow-up 19.5 months). In each interval,
      patients were considered 'adherent' to AH and LL therapy if they had filled
      prescriptions sufficient to cover>or=80% of days with both medication classes. A
      multivariable regression model evaluated potential predictors of adherence to
      concomitant therapy, including patient demographics, clinical characteristics and
      health services use patterns at baseline. RESULTS: The percentage of patients
      adherent to both AH and LL therapy declined rapidly, before stabilizing, with
      40.5%, 32.7% and 32.9% adherent at 3, 6 and 12 months, respectively. At each
      timepoint, an additional 27.8-35.0% of patients were adherent to either AH or LL
      therapy, but not both. Adherence was on average greater to AH than LL therapy.
      After adjusting for age, sex and other potential predictors, patients were more
      likely to be adherent if AH/LL therapies were initiated closer together in time
      (adjusted odds ratio [AOR] 1.13 for 0-30 days vs 61-90 days, p=0.0563), had a
      history of cardiovascular disease (AOR 1.27, p=0.0004), took fewer additional
      medications (AOR 0.43 for six or more medications vs zero or one medication,
      p<0.0001) or had more outpatient physician visits in the prior year (AOR 1.26 for
      four to six visits vs zero to one visit, p<0.0027). CONCLUSION: Adherence to
      concomitant AH and LL therapy among older adults is poor. Modifiable factors that
      may improve adherence in Medicare-eligible patients include initiating therapy
      concurrently and reducing patients' overall pill burden.

PMID- 18808214
TI  - Contaminated suspended sediments toxic to an Antarctic filter feeder: aqueous-
      and particulate-phase effects.
AB  - Disturbances such as dredging, storms, and bioturbation result in the
      resuspension of sediments. This may affect sessile organisms that live on hard
      substrates directly above the sediment. Localized sediment contamination exists
      around many Antarctic research stations, often resulting in elevated
      contamination loads in marine sediments. To our knowledge, the potential impact
      of resuspended contaminated sediments on sessile fauna has not been considered,
      so in the present study, we assessed the sensitivity of Antarctic spirorbid
      polychaetes to aqueous metals and to metal-contaminated sediments that had been
      experimentally resuspended. Worms were first exposed to aqueous metals, both
      singly and in combination, over 10 d. Spirorbid mortality was tolerant to copper
      (median lethal concentration [LC50], 570 microg/L), zinc (LC50, > 4,910
      microg/L), and lead (LC50, > 2,905 microg/L); however, spirorbid behavior
      responded to copper concentrations as low as 20 microg/L. When in combination,
      zinc significantly reduced mortality caused by copper. A novel technique was used
      to resuspend sediments spiked with four concentrations of three metals (up to 450
      microg/g dry wt of copper, 525 micro/g dry wt of lead, and 2,035 microg/g dry wt
      of zinc). The response of spirorbids to unfiltered suspended sediment solutions
      and filtered solutions (aqueous metal exposure) was measured. Suspended sediments
      were toxic to filter-feeding spirorbids at concentrations approximating those
      found in contaminated Antarctica areas. Toxicity resulted both from aqueous
      metals and from metals associated with the suspended sediments, although
      suspended clean sediments had no impact. To our knowledge, the present study is
      the first to show that resuspension of contaminated sediments can be an important
      pathway for toxicity to Antarctic hard substrate organisms. Based on the present
      results, current sediment-quality guidelines used in the evaluation of Australian
      sediments may be applicable to Antarctic ecosystems.

PMID- 18808215
TI  - Enterovirus is not present in placentas from cases of perinatal depression using
      polymerase chain reaction analysis.
AB  - Enteroviruses have been implicated as a cause of low Apgar scores in conjunction
      with perinatal seizures and respiratory insufficiency. Using in-situ reverse
      transcriptase polymerase chain reaction (in-situ PCR), Nuovo et al detected
      enterovirus in up to 86% of placentas from perinates exhibiting these symptoms.
      In-situ PCR has been the only method employed to assess for the presence
      ofenterovirus in this specific patient population. The purpose of our study was
      to use PCR amplification of enterovirus from extracted RNA to confirm these
      observations. RNA was extracted from 26 placentas of infants with low Apgar
      scores, perinatal seizures, and respiratory insufficiency. Each extraction was
      positive for beta-actin RNA, which confirmed that the integrity of RNA was
      maintained in the sample. Enterovirus RNA was not detected in any of the cases.
      Our results indicate that enterovirus is not present in placentas from neonates
      with the combination of low Apgar scores, respiratory insufficiency, and
      seizures, as previously reported.

PMID- 18808216
TI  - Clonal variation in physiological responses of Daphnia magna to the strobilurin
      fungicide azoxystrobin.
AB  - Because of its high grazing potential, Daphnia magna is an ecologically important
      species in aquatic food webs. This is especially true in small, shallow ponds
      lacking fish, where grazing by D. magna may have a relatively higher impact on
      water clarity as compared to larger lakes. Thus, a reduction in daphnid abundance
      may have dramatic ecological consequences for shallow ponds. At the same time,
      shallow ponds in close proximity to agricultural areas likely experience higher
      concentrations of pesticides because of runoff, spray drift, and drain flow. In
      the present study, the acute and chronic physiological effects of the strobilurin
      fungicide azoxystrobin on three clones of D. magna originating from different
      Danish lakes were evaluated. Significant clonal variation in the sensitivity of
      D. magna toward azoxystrobin was demonstrated. One clone had a 48-h median lethal
      concentration (LC50) of 0.277 mg/L (95% confidence limits [CL], 0.145 and 0.427
      mg/L), which is comparable to the value widely used in risk assessments (0.259
      mg/L). The two remaining clones were far more sensitive, however, and had LC50s
      of 0.071 mg/L (95% CL, 0.034 and 0.126 mg/L) and 0.098 mg/L (95% CL, 0.066 and
      0.139 mg/L), respectively. Furthermore, through respiration measurements and life
      table experiments, sublethal stress was shown to exist at exposure to an
      ecologically relevant concentration (0.026 microg/L). Based on these results, we
      may expect changes in daphnid populations at azoxystrobin concentrations much
      lower than previously thought. Thus, ponds in the agricultural areas may
      experience changes in food-web structure even at very low concentrations of
      azoxystrobin.

PMID- 18808217
TI  - Peroxidase-mediated degradation of perfluorooctanoic acid.
AB  - Concentrations of aqueous-phase perfluorooctanoic acid (PFOA), a representative
      perfluorinated aliphatic (PFA) compound, are shown to be reduced effectively via
      reaction with horseradish peroxidase (HRP), hydrogen peroxide, and a phenolic
      cosubstrate (4-methoxyphenol). Reaction rate profiles are pseudo-first order,
      yielding an apparent best-fit removal rate constant of k1 = 0.003/min (r2 = 0.96,
      n = 14). Approximately 68% depletion of the parent compound and 98% depletion of
      its related acute aquatic toxicity are achieved in 6 h. Because no PFOA removal
      is observed in the absence of cosubstrate and/or following consumption thereof,
      we conclude that radical intermediate species generated during reaction between
      HRP and 4-methoxyphenol mediate nonspecific depletion of PFOA and that these
      intermediates may be sufficiently reactive to sever the extremely stable C-F
      bonds of PFOA. These results are consistent with measurements of reaction by
      products, including fluoride ion and various aliphatic species of shortened chain
      length. Based on these findings, we conclude that PFA degradation may occur via
      one of two mechanisms: Kolbe decarboxylation followed by stepwise conversion of 
      CF2 units to CO2 and fluoride ion, or radical abstraction from a double bond with
      subsequent fragmentation. Our results indicate that under appropriate conditions,
      enzymatic degradation may comprise a natural transformation pathway for PFAs.
      Moreover, we anticipate that appropriately engineered enzymatic processes may
      hold promise for treatment of PFOA-contaminated waters. This, to the best of our
      knowledge, is the first report to substantiate the efficacy of HRP-catalyzed
      reactions for contaminant removal via degradative reactions versus polymerization
      reactions.

PMID- 18808218
TI  - Affective mechanisms linking dysfunctional behavior to performance in work teams:
      a moderated mediation study.
AB  - The present study examines the association between dysfunctional team behavior
      and team performance. Data included measures of teams' dysfunctional behavior and
      negative affective tone as well as supervisors' ratings of teams' (nonverbal)
      negative emotional expressivity and performance. Utilizing a field sample of 61
      work teams, the authors tested the proposed relationships with robust data
      analytic techniques. Results were consistent with the hypothesized conceptual
      scheme, in that negative team affective tone mediated the relationship between
      dysfunctional team behavior and performance when teams' nonverbal negative
      expressivity was high but not when nonverbal expressivity was low. On the basis
      of the findings, the authors conclude that the connection between dysfunctional
      behavior and performance in team situations is more complex than was previously
      believed--thereby yielding a pattern of moderated mediation. In sum, the findings
      demonstrated that team members' collective emotions and emotional processing
      represent key mechanisms in determining how dysfunctional team behavior is
      associated with team performance.

PMID- 18808219
TI  - Ill-structured measurement designs in organizational research: implications for
      estimating interrater reliability.
AB  - Organizational research and practice involving ratings are rife with what the
      authors term ill-structured measurement designs (ISMDs)--designs in which raters
      and ratees are neither fully crossed nor nested. This article explores the
      implications of ISMDs for estimating interrater reliability. The authors first
      provide a mock example that illustrates potential problems that ISMDs create for
      common reliability estimators (e.g., Pearson correlations, intraclass
      correlations). Next, the authors propose an alternative reliability estimator-
      G(q,k)--that resolves problems with traditional estimators and is equally
      appropriate for crossed, nested, and ill-structured designs. By using Monte Carlo
      simulation, the authors evaluate the accuracy of traditional reliability
      estimators compared with that of G(q,k) for ratings arising from ISMDs.
      Regardless of condition, G(q,k) yielded estimates as precise or more precise than
      those of traditional estimators. The advantage of G(q,k) over the traditional
      estimators became more pronounced with increases in the (a) overlap between the
      sets of raters that rated each ratee and (b) ratio of rater main effect variance
      to true score variance. Discussion focuses on implications of this work for
      organizational research and practice.

PMID- 18808220
TI  - Managing discrimination in selection: the influence of directives from an
      authority and social dominance orientation.
AB  - The authors examined one manner in which to decrease the negative impact of
      social dominance orientation (SDO), an individual difference variable that
      indicates support for the "domination of 'inferior' groups by 'superior' groups"
      (J. Sidanius & F. Pratto, 1999, p. 48), on the selection of candidates from low
      status groups within society. Consistent with the tenets of social dominance
      theory, in 2 studies we found that those high in SDO reported that they were less
      likely to select a potential team member who is a member of a low-status group
      (i.e., a White female in Study 1 and a Black male in Study 2) than those low in
      SDO. However, explicit directives from an authority moderated this effect such
      that those high in SDO were more likely to select both candidates when authority
      figures clearly communicated that job performance indicators should be used when
      choosing team members. Thus, our studies suggest that the negative effects of SDO
      may be attenuated if those high in SDO are instructed by superiors to use
      legitimate performance criteria to evaluate job candidates.

PMID- 18808221
TI  - Is the gap more than gender? A longitudinal analysis of gender, gender role
      orientation, and earnings.
AB  - This study investigated the relationships among gender, gender role orientation
      (i.e., attitudes toward the gendered separation of roles at work and at home),
      and earnings. A multilevel model was conceptualized in which gender role
      orientation and earnings were within-individual variables that fluctuate over
      time (although predictors of between-individual differences in gender role
      orientation were also considered). Results indicated that whereas traditional
      gender role orientation was positively related to earnings, gender significantly
      predicted the slope of this relationship: Traditional gender role orientation was
      strongly positively associated with earnings for men; it was slightly negatively
      associated with earnings for women. Occupational segregation partly explained
      these gender differences. Overall, the results suggest that although gender role
      attitudes are becoming less traditional for men and for women, traditional gender
      role orientation continues to exacerbate the gender wage gap.

PMID- 18808222
TI  - Volunteer recruitment: the role of organizational support and anticipated respect
      in non-volunteers' attraction to charitable volunteer organizations.
AB  - In 3 experiments the authors examined how specific characteristics of charitable
      volunteer organizations contribute to the recruitment of new volunteers. In line
      with predictions, Study 1 revealed that providing non-volunteers with information
      about organizational support induced anticipated feelings of respect, which
      subsequently enhanced their attraction to the volunteer organization. However,
      information about the current success of the volunteer organization did not
      affect anticipated pride (as among those who seek paid employment) and in fact
      caused potential volunteers to perceive the organization as being in less need
      for additional volunteers. Study 2 further showed that information about support
      from the volunteer organization is a more relevant source of anticipated respect
      and organizational attraction than support from co-volunteers. Study 3 finally
      showed that information about task and emotional support for volunteers
      contributes to anticipated respect and organizational attractiveness and that
      this increases the actual willingness of non-volunteers to participate in the
      volunteer organization. Interventions aimed at attracting volunteers and avenues
      for further research are discussed.

PMID- 18808223
TI  - Moral attentiveness: who pays attention to the moral aspects of life?
AB  - This research draws from social cognitive theory to develop a construct known as
      moral attentiveness, the extent to which an individual chronically perceives and
      considers morality and moral elements in his or her experiences, and proposes
      that moral attentiveness affects a variety of behaviors. A series of 5 studies
      with undergraduates, MBA students, and managers were conducted to create and
      validate a reliable multidimensional scale and to provide evidence that moral
      attentiveness is associated with (a) the recall and reporting of self- and
      others' morality-related behaviors, (b) moral awareness, and (c) moral behavior.
      Results of the studies suggest that moral attentiveness has a significant effect
      on how individuals understand and act in their moral worlds.

PMID- 18808224
TI  - Further evidence for the validity of assessment center dimensions: a meta
      analysis of the incremental criterion-related validity of dimension ratings.
AB  - This study investigates the incremental variance in job performance explained by
      assessment center (AC) dimensions over and above personality and cognitive
      ability. The authors extend previous research by using meta-analysis to examine
      the relationships between AC dimensions, personality, cognitive ability, and job
      performance. The results indicate that the 7 summary AC dimensions postulated by
      W. Arthur, Jr., E. A. Day, T. L. McNelly, & P. S. Edens (2003) are
      distinguishable from popular individual difference constructs and explain a
      sizeable proportion of variance in job performance beyond cognitive ability and
      personality.

PMID- 18808225
TI  - The effect of gender stereotype activation on entrepreneurial intentions.
AB  - In this study, the impact of implicit and explicit activation of gender
      stereotypes on men's and women's intentions to pursue a traditionally masculine
      career, such as entrepreneurship, was examined. On the basis of stereotype
      activation theory, it was hypothesized that men and women would confirm the
      gender stereotype about entrepreneurship when it was presented implicitly but
      disconfirm it when it was presented explicitly. Hypotheses were tested by
      randomly assigning 469 business students to one of 6 experimental conditions and
      then measuring their entrepreneurial intentions. Results supported the hypothesis
      when entrepreneurship was associated with stereotypically masculine
      characteristics but not when it was associated with traditionally feminine
      characteristics. Men also had higher entrepreneurial intention scores compared
      with women when no stereotypical information about entrepreneurship was
      presented, suggesting that underlying societal stereotypes associating
      entrepreneurship with masculine characteristics may influence people's
      intentions. However, men and women reported similar intentions when
      entrepreneurship was presented as gender neutral, suggesting that widely held
      gender stereotypes can be nullified. Practical implications and directions for
      future research are discussed.

PMID- 18808226
TI  - Research in industrial and organizational psychology from 1963 to 2007: changes,
      choices, and trends.
AB  - The authors conducted a content analysis of all articles published in the Journal
      of Applied Psychology and Personnel Psychology from January 1963 to May 2007 (N =
      5,780) to identify the relative attention devoted to each of 15 broad topical
      areas and 50 more specific subareas in the field of industrial and organizational
      (I-O) psychology. Results revealed that (a) some areas have become more (or less)
      popular over time, whereas others have not changed much, and (b) there are some
      lagged relationships between important societal issues that involve people and
      work settings (i.e., human-capital trends) and I-O psychology research that
      addresses them. Also, much I-O psychology research does not address human-capital
      trends. Extrapolating results from the past 45 years to the next decade suggests
      that the field of I-O psychology is not likely to become more visible or more
      relevant to society at large or to achieve the lofty goals it has set for itself
      unless researchers, practitioners, universities, and professional organizations
      implement significant changes. In the aggregate, the changes address the broad
      challenge of how to narrow the academic-practitioner divide.

PMID- 18808227
TI  - Do peers make the place? Conceptual synthesis and meta-analysis of coworker
      effects on perceptions, attitudes, OCBs, and performance.
AB  - The authors propose that broad aspects of lateral relationships, conceptualized
      as coworker support and coworker antagonism, are linked to important individual
      employee outcomes (role perceptions, work attitudes, withdrawal, and
      effectiveness) in a framework that synthesizes several theoretical predictions.
      From meta-analytic tests based on 161 independent samples and 77,954 employees,
      the authors find support for most of the proposed linkages. Alternative
      explanations are ruled out, as results hold when controlling for leader
      influences and mediation processes. The authors also observe differential
      strengths of coworker influence based on its valence, content, and severity, and
      on the social intensity of the task environment. The authors conclude with a call
      for more comprehensive, complex theory and investigation of coworker influences
      as part of the social environment at work.

PMID- 18808228
TI  - When employees strike back: investigating mediating mechanisms between
      psychological contract breach and workplace deviance.
AB  - In this article, psychological contract breach, revenge, and workplace deviance
      are brought together to identify the cognitive, affective, and motivational
      underpinnings of workplace deviance. On the basis of S. L. Robinson and R. J.
      Bennett's (1997) model of workplace deviance, the authors proposed that breach (a
      cognitive appraisal) and violation (an affective response) initiate revenge
      seeking. Motivated by revenge, employees then engage in workplace deviance. Three
      studies tested these ideas. All of the studies supported the hypothesized
      relationships. In addition, self-control was found to be a moderator of the
      relationship between revenge cognitions and deviant acts; the relationship was
      weaker for people high in self-control.

PMID- 18808229
TI  - Differences between African Americans and Whites in reactions to affirmative
      action programs in hiring, promotion, training, and layoffs.
AB  - This study examines the reactions of African Americans and Whites to affirmative
      action programs (AAPs) applied to 4 human resource activities: hiring, promotion,
      training, and layoffs. The results of a scenario-based experimental study
      conducted on a large sample (N > 800) of advanced undergraduate and MBA business
      school participants generally supported the hypothesis that human resource
      activity elicited systematic differences in reaction to AAPs between African
      Americans and Whites. The authors also replicated previous research on the effect
      of AAP strength and prior discrimination by the organization on reactions to
      AAPs. Results indicated that AAP strength levels moderated racial differences in
      reaction to AAPs, while the moderating role of prior discrimination by the
      organization was not supported. Implications for future research are discussed.

PMID- 18808230
TI  - Antecedents of coworker trust: leaders' blessings.
AB  - Although employee trust in leaders has garnered substantial empirical research,
      trust between coworkers has been virtually ignored. Extending the work of D. L.
      Ferrin, K. T. Dirks, and P. P. Shah (2006), the authors examined the role of
      group leaders, an influential third party in the workplace, on coworker trust
      formation. The correlates of the extent to which coworkers trust one another were
      examined in an investigation of 146 members of 32 work groups representing 4
      diverse organizations. In this study, which utilized full network data, coworker
      trust was operationalized as in-degree centrality in the trust network.
      Controlling for relational demography and coworker helping behaviors, the authors
      found, as hypothesized, that coworkers tended to place more trust in fellow
      coworkers who were also trusted by the teams' formal leaders than in coworkers
      who were less trusted by leaders. In addition, consistent with the social
      information processing theory, support was found for the hypothesis that the
      relationship between leaders' trust and coworker trust is stronger when group
      performance is poor.

PMID- 18808231
TI  - Exploring the handshake in employment interviews.
AB  - The authors examined how an applicant's handshake influences hiring
      recommendations formed during the employment interview. A sample of 98
      undergraduate students provided personality measures and participated in mock
      interviews during which the students received ratings of employment suitability.
      Five trained raters independently evaluated the quality of the handshake for each
      participant. Quality of handshake was related to interviewer hiring
      recommendations. Path analysis supported the handshake as mediating the effect of
      applicant extraversion on interviewer hiring recommendations, even after
      controlling for differences in candidate physical appearance and dress. Although
      women received lower ratings for the handshake, they did not on average receive
      lower assessments of employment suitability. Exploratory analysis suggested that
      the relationship between a firm handshake and interview ratings may be stronger
      for women than for men.

PMID- 18808232
TI  - Organizational injury rate underreporting: the moderating effect of
      organizational safety climate.
AB  - The goals of this study were (a) to assess the extent to which construction
      industry workplace injuries and illness are underreported, and (b) to determine
      whether safety climate predicts the extent of such underreporting. Data from
      1,390 employees of 38 companies contracted to work at a large construction site
      in the northwestern United States were collected to assess the safety climate of
      the companies. Data from the Occupational Safety and Health Administration (OSHA)
      logs kept by the contractors allowed for calculation of each company's OSHA
      recordable injury rate (i.e., the reported injury rate), whereas medical claims
      data from an Owner-Controlled Insurance Program provided the actual experienced
      rate of injuries for those same companies. While the annual injury rate reported
      to OSHA was 3.11 injuries per 100 workers, the rate of eligible injuries that
      were not reported to OSHA was 10.90 injuries per 100 employees. Further,
      organizations with a poor safety climate had significantly higher rates of
      underreporting (81% of eligible injuries unreported) compared with organizations
      with a positive safety climate (47% of eligible injuries unreported).
      Implications for organizations and the accuracy of the Bureau of Labor
      Statistics's national occupational injury and illness surveillance system are
      discussed.

PMID- 18808233
TI  - The ripple effect of personality on social structure: self-monitoring origins of
      network brokerage.
AB  - Despite growing interest in social network brokerage, its psychological
      antecedents have been neglected. One possibility is that brokerage relates to
      self-monitoring personality orientation. High self-monitors, relative to low self
      monitors, in adapting their self-presentations to the demands of different
      groups, may occupy positions as brokers between disconnected social worlds. For
      162 Korean expatriate entrepreneurs in a Canadian urban area, the results showed
      that those high in self-monitoring tended to occupy direct brokerage roles within
      the Korean community--in terms of their direct acquaintances being unconnected
      with each other. Those high in self-monitoring also tended to occupy indirect
      brokerage roles--in terms of the acquaintances of their acquaintances being
      unconnected with each other. Finally, for recent arrivals, those high in self
      monitoring tended to establish ties to a wider range of important non-Korean
      position holders outside the community. These results (which controlled for
      strongly significant effects of network size on individuals' brokerage within the
      community) suggest a ripple effect of self-monitoring on social structure and
      contribute to a clearer understanding of how personality relates to brokerage at
      different levels.

PMID- 18808234
TI  - Blinded by anger or feeling the love: how emotions influence advice taking.
AB  - Across 2 experiments, the authors demonstrate that emotional states influence how
      receptive people are to advice. The focus of these experiments is on incidental
      emotions, emotions triggered by a prior experience that is irrelevant to the
      current situation. The authors demonstrate that people who feel incidental
      gratitude are more trusting and more receptive to advice than are people in a
      neutral emotional state, and people in a neutral state are more trusting and more
      receptive to advice than are people who feel incidental anger. In these
      experiments, greater receptivity to advice increased judgment accuracy. People
      who felt incidental gratitude were more accurate than were people in a neutral
      state, and people in a neutral state were more accurate than were people who felt
      incidental anger. The results offer insight into how people use advice, and the
      authors identify conditions under which leaders, policy makers, and advisors may
      be particularly influential.

PMID- 18808235
TI  - Personal and task-related moderators of leader-member exchange among software
      developers.
AB  - Although earlier studies have shown significant positive relationships between
      leader-member exchange (LMX) and its outcomes, they have also noted that the
      effect sizes of these relationships have been modest and heterogeneous.
      Addressing numerous calls for future studies that examine potential moderators of
      the LMX-job performance and LMX-job satisfaction relationships and utilizing a
      multidomain perspective, this study tests the moderating roles of personal (i.e.,
      locus of control) and task-related (i.e., task autonomy) factors on these
      relationships. The results of an empirical study with a sample of 287 software
      developers and 164 supervisors participating at a large international information
      technology exhibition indicated that the LMX-job performance relationship was
      stronger when employees' locus of control was internal as opposed to when it was
      external. In addition, it was stronger when task autonomy was high as opposed to
      when it was low. Moreover, the results suggested that the LMX-job satisfaction
      relationship was stronger when task autonomy was high as opposed to when it was
      low. Finally, contrary to theoretical expectations, employees' locus of control
      did not moderate the LMX-job satisfaction relationship.

PMID- 18808236
TI  - Conscientiousness and reactions to psychological contract breach: a longitudinal
      field study.
AB  - The authors examined the role of employee conscientiousness as a moderator of the
      relationships between psychological contract breach and employee behavioral and
      attitudinal reactions to the breach. They collected data from 106 newly hired
      employees within the 1st month of employment (Time 1), 3 months later (Time 2),
      and 8 months after Time 1 (Time 3) to observe the progression through contract
      development, breach, and reaction. Results suggest that conscientiousness is a
      significant moderator for 4 of the 5 contract breach-employee reaction
      relationships examined (turnover intentions, organizational loyalty, job
      satisfaction, and 1 of 2 facets of job performance). Specifically, employees who
      were lower in conscientiousness had more negative reactions to perceived breach
      with respect to turnover intentions, organizational loyalty, and job
      satisfaction. In contrast, employees who were higher in conscientiousness reduced
      their job performance to a greater degree in response to contract breach. Future
      research directions are discussed.

PMID- 18808239
TI  - Me against myself: motivational conflicts and emotional development in adulthood.
AB  - Two studies investigated adult age differences in the frequency and emotional
      consequences of motivational conflicts (i.e., feeling that one wants to or should
      do something else in a given situation). Study 1 compared younger and older
      adults. Study 2 included a more age-heterogeneous sample ranging from 20 to 70
      years. Data were obtained using diary and experience-sampling methods. Multilevel
      regression showed that motivational conflict was associated with lower emotional
      well-being. With age, the frequency of motivational conflict decreased, while
      emotional well-being increased. Importantly, the age-related decrease in
      motivational conflicts partly accounted for the age-related increase in emotional
      well-being. Findings were consistent across studies and robust after the authors
      controlled for age differences in a number of control variables including time
      use. The authors conclude that an age-related decrease in motivational conflicts
      in daily life may be among the factors underlying the positive development of
      emotional well-being into older adulthood.

PMID- 18808240
TI  - Unpleasant situations elicit different emotional responses in younger and older
      adults.
AB  - Older adults report less distress in response to interpersonal conflicts than do
      younger adults, yet few researchers have examined factors that may contribute to
      these age differences. Emotion regulation is partially determined by the initial
      cognitive and emotional reactions that events elicit. The authors examined
      reported thoughts and emotions of younger and older adults (N = 195) while they
      listened to 3 different audiotaped conversations in which people were ostensibly
      making disparaging remarks about them. At 4 points during each scenario, the tape
      paused and participants engaged in a talk-aloud procedure and rated their level
      of anger and sadness. Findings reveal that older adults reported less anger but
      equal levels of sadness compared to younger adults, and their comments were
      judged by coders as less negative. Older adults made fewer appraisals about the
      people speaking on the tape and expressed less interest in learning more about
      their motives. Together, findings are consistent with age-related increases in
      processes that promote disengagement from offending situations.

PMID- 18808241
TI  - Collaborative coping and daily mood in couples dealing with prostate cancer.
AB  - Collaborative coping (i.e., spouses pooling resources and problem solving
      jointly) may be associated with better daily mood because of heightened
      perceptions of efficacy in coping with stressful events. The study examined the
      daily processes of collaborative coping (individuals' perceptions that the spouse
      collaborated), perceived coping effectiveness (ratings of how well they dealt
      with the event), and mood (i.e., Positive and Negative Affect Scale) across 14
      days in 57 older couples coping with stressors involving the husband's prostate
      cancer and daily life in general. In hierarchical multivariate linear models,
      collaborative coping was associated with more positive same-day mood for both
      husbands and wives and less negative mood for wives only. These associations were
      partially mediated by heightened perceptions of coping effectiveness. Exploratory
      analyses revealed that collaborative coping was more frequent among wives who
      performed more poorly on cognitive tests and couples who reported greater marital
      satisfaction and more frequently using collaboration to make decisions. The
      results suggest that older couples may benefit from collaborative coping in
      dealing with problems surrounding illness.

PMID- 18808242
TI  - Collaborative everyday problem solving among same-gender friends in early and
      later adulthood.
AB  - To investigate potential age-related differences in performance gains
      (compensation and optimization) and losses (failure to actualize potential) of
      collaboration with a familiar partner, the authors compared pairs of older (N =
      75; 69% women) and younger (N = 75; 52% women) age-homogeneous same-gender
      friends who interacted or worked alone to generate strategies for solving
      interpersonal and instrumental problems. Two indexes of strategy fluency (total
      and unique number of strategies) and 2 indexes of strategy type (content of
      strategy repertoires and strategy selected as most effective by older and younger
      adults) were examined. Strategies generated by interacting pairs were compared
      with nominal pair scores. Nominal pair scores indexed dyadic potential and were
      created by pooling the performance of 2 individuals who worked alone. Age
      differences in strategy fluency and type were largely similar to prior research
      based on individual problem solvers. Interacting pairs produced fewer strategies
      than nominal pairs, but there were no differences in strategy type. For
      interpersonal problems, older adults were relatively more likely to actualize
      their dyadic potential.

PMID- 18808243
TI  - Adult age differences in the realism of confidence judgments: overconfidence,
      format dependence, and cognitive predictors.
AB  - Realistic confidence judgments are essential to everyday functioning, but few
      studies have addressed the issue of age differences in overconfidence. Therefore,
      the authors examined this issue with probability judgment and intuitive
      confidence intervals in a sample of 122 healthy adults (ages: 35-40, 55-60, 70-75
      years). In line with predictions based on the naive sampling model (P. Juslin, A.
      Winman, & P. Hansson, 2007), substantial format dependence was observed, with
      extreme overconfidence when confidence was expressed as an intuitive confidence
      interval but not when confidence was expressed as a probability judgment.
      Moreover, an age-related increase in overconfidence was selectively observed when
      confidence was expressed as intuitive confidence intervals. Structural equation
      modeling indicated that the age-related increases in overconfidence were mediated
      by a general cognitive ability factor that may reflect executive processes.
      Finally, the results indicated that part of the negative influence of increased
      age on general ability may be compensated for by an age-related increase in
      domain-relevant knowledge.

PMID- 18808244
TI  - Long-term correlated change in personality traits in old age.
AB  - The present study examines long-term correlated change in personality traits in
      old age across a time period of 12 years. Data from the Interdisciplinary Study
      on Adult Development were used to investigate different aspects of personality
      change and stability. The sample consisted of 300 adults ranging from 60 to 64
      years of age at Time 1. Personality was measured with the NEO Five-Factor
      Inventory. Longitudinal structural stability, differential stability, change in
      interindividual differences, mean-level change, and correlated change of the 5
      personality traits were examined utilizing structural equation modeling. After
      having established strict measurement invariance, factor variances in Openness to
      Experience and Conscientiousness were found to be different across testing
      occasions, implying variant covariation patterns over time. Stability
      coefficients were around .70, indicating high but not perfect differential
      stability. The amount of interindividual differences increased with respect to
      Openness to Experience and Conscientiousness. Both mean-level change and
      stability in personality were observed. Eventually, except for Neuroticism, a
      number of medium effect-sized correlations among changes in personality traits
      emerged, implying that personality changes share a substantial amount of
      commonality.

PMID- 18808245
TI  - Age differences in the Big Five across the life span: evidence from two national
      samples.
AB  - Cross-sectional age differences in the Big Five personality traits were
      investigated using 2 large datasets from Great Britain and Germany: the British
      Household Panel Study (BHPS; N > or = 14,039) and the German Socio-Economic Panel
      Study (GSEOP; N > or = 20,852). Participants, who ranged in age from 16 to the
      mid-80s, completed a 15-item version of the Big Five Inventory (e.g., John &
      Srivastava, 1999) in either 2005 or 2006. The observed age trends were generally
      consistent across both datasets. Extraversion and Openness were negatively
      associated with age, whereas Agreeableness was positively associated with age.
      Average levels of Conscientiousness were highest for participants in middle age.
      The only exception was Neuroticism, which was slightly negatively associated with
      age in the BHPS and slightly positively associated with age in the GSEOP. Neither
      gender nor education level were consistent moderators of age differences in the
      Big Five.

PMID- 18808246
TI  - The four-factor model of depressive symptoms in dementia caregivers: a structural
      equation model of ethnic differences.
AB  - Previous studies have suggested that 4 latent constructs (depressed affect, well
      being, interpersonal problems, somatic symptoms) underlie the item responses on
      the Center for Epidemiological Studies Depression (CES-D) Scale. This instrument
      has been widely used in dementia caregiving research, but the fit of this
      multifactor model and the explanatory contributions of multifactor models have
      not been sufficiently examined for caregiving samples. The authors subjected CES
      D data (N = 1,183) from the initial Resources for Enhancing Alzheimer's Caregiver
      Health Study to confirmatory factor analysis methods and found that the 4-factor
      model provided excellent fit to the observed data. Invariance analyses suggested
      only minimal item-loading differences across race subgroups and supported the
      validity of race comparisons on the latent factors. Significant race differences
      were found on 3 of the 4 latent factors both before and after controlling for
      demographic covariates. African Americans reported less depressed affect and
      better well-being than White caregivers, who reported better well-being and fewer
      interpersonal problems than Hispanic caregivers. These findings clarify and
      extend previous studies of race differences in depression among diverse samples
      of dementia caregivers.

PMID- 18808247
TI  - Characteristics of problem gamblers 56 years of age or older: a statewide study
      of casino self-excluders.
AB  - Gambling among older adults appears to be increasing, though little is known
      about the characteristics of older adult problem gamblers. The purpose of this
      study was to compare older adults to younger and middle-aged adults in a cohort
      of problem gamblers participating in a state-administered casino self-exclusion
      program. Self-reported problem gamblers (N = 1,601) who voluntary banned
      themselves from Missouri casinos from 2001 to 2003 were categorized by age as
      younger adults (ages 21 to 35; n = 490), middle-aged adults (ages 36 to 55; n =
      950), and older adults (ages 56 to 79; n = 161), and were compared with respect
      to demographic variables, gambling participation, and reasons for self-exclusion.
      Older adult self-excluders typically began gambling in midlife, experienced
      gambling problems around age 60, reported preferences for nonstrategic forms of
      gambling, and identified fear of suicide as the primary reason for self
      excluding. Implications for intervention, prevention and treatment are discussed.

PMID- 18808248
TI  - Cognitive resources, valence, and memory retrieval of emotional events in older
      adults.
AB  - In 2 studies with older adults, the authors investigated the effect of executive
      attention resources on the retrieval of emotional public events. Participants
      completed a battery of working memory tasks, as a measure of executive attention,
      and a battery of tasks assessing memory, as well as subjective experiences
      associated with the retrieval of remote public events. Participants also rated
      the valence of each public event story. The group-rated valence of the public
      event stories predicted retrieval and the quality of experiences associated with
      them, such that emotionally arousing events elicited the highest memory rates and
      the richest experiences. Furthermore, positive public events elicited the highest
      memory rates. Executive attention moderated only the relationship between event
      valence and how participants' associated memories are experienced at retrieval,
      such that superior executive attention resources predicted richer experiences
      associated with positive relative to neutral and negative stories. The current
      results extend previous findings on the effects of aging on emotion regulation,
      suggesting that cognitive control resources modulate subjective experiences
      associated with retrieved memories for remote real life events, but not memory
      retrieval itself.

PMID- 18808249
TI  - Predicting impending death: inconsistency in speed is a selective and early
      marker.
AB  - Among older adults, deficits in both level and variability of speeded performance
      are linked to neurological impairment. This study examined whether and when speed
      (rate), speed (inconsistency), and traditional accuracy-based markers of
      cognitive performance foreshadow terminal decline and impending death. Victoria
      Longitudinal Study data spanning 12 years (5 waves) of measurement were assembled
      for 707 adults aged 59 to 95 years. Whereas 442 survivors completed all waves and
      relevant measures, 265 decedents participated on at least 1 occasion and
      subsequently died. Four main results were observed. First, Cox regressions
      evaluating the 3 cognitive predictors of mortality replicated previous results
      for cognitive accuracy predictors. Second, level (rate) of speeded performance
      predicted survival independent of demographic indicators, cardiovascular health,
      and cognitive performance level. Third, inconsistency in speed predicted survival
      independent of all influences combined. Fourth, follow-up random-effects models
      revealed increases in inconsistency in speed per year closer to death, with
      advancing age further moderating the accelerated growth. Hierarchical prediction
      patterns support the view that inconsistency in speed is an early behavioral
      marker of neurological dysfunction associated with impending death.

PMID- 18808250
TI  - Gender and education impact on brain aging: a general cognitive factor approach.
AB  - In cognitive aging research, the study of a general cognitive factor has been
      shown to have a substantial explanatory power over the study of isolated tests.
      The authors aimed at differentiating the impact of gender and education on global
      cognitive change with age from their differential impact on 4 psychometric tests
      using a new latent process approach, which intermediates between a single-factor
      longitudinal model for sum scores and an item-response theory approach for
      longitudinal data. The analysis was conducted on a sample of 2,228 subjects from
      PAQUID, a population-based cohort of older adults followed for 13 years with
      repeated measures of cognition. Adjusted for vascular factors, the analysis
      confirmed that women performed better in tests involving verbal components, while
      men performed better in tests involving visuospatial skills. In addition, the
      model suggested that women had a slightly steeper global cognitive decline with
      oldest age than men, even after excluding incident dementia or death. Subjects
      with higher education exhibited a better mean score for the 4 tests, but this
      difference tended to attenuate with age for tests involving a speed component.

PMID- 18808251
TI  - Oh, honey, I already forgot that: strategic control of directed forgetting in
      older and younger adults.
AB  - Two experiments investigated list-method directed forgetting with older and
      younger adults. Using standard directed forgetting instructions, significant
      forgetting was obtained with younger but not older adults. However, in Experiment
      1 older adults showed forgetting with an experimenter-provided strategy that
      induced a mental context change--specifically, engaging in diversionary thought.
      Experiment 2 showed that age-related differences in directed forgetting occurred
      because older adults were less likely than younger adults to initiate a strategy
      to attempt to forget. When the instructions were revised to downplay their
      concerns about memory, older adults engaged in effective forgetting strategies
      and showed significant directed forgetting comparable in magnitude to younger
      adults. The results highlight the importance of strategic processes in directed
      forgetting.

PMID- 18808252
TI  - Age differences in proactive interference, working memory, and abstract
      reasoning.
AB  - It has been hypothesized that older adults are especially susceptible to
      proactive interference (PI) and that this may contribute to age differences in
      working memory performance. In young adults, individual differences in PI affect
      both working memory and reasoning ability, but the relations between PI, working
      memory, and reasoning in older adults have not been examined. In the current
      study, young, old, and very old adults performed a modified operation span task
      that induced several cycles of PI buildup and release as well as two tests of
      abstract reasoning ability. Age differences in working memory scores increased as
      PI built up, consistent with the hypothesis that older adults are more
      susceptible to PI, but both young and older adults showed complete release from
      PI. Young adults' reasoning ability was best predicted by working memory
      performance under high PI conditions, replicating M. Bunting (2006). In contrast,
      older adults' reasoning ability was best predicted by their working memory
      performance under low PI conditions, thereby raising questions regarding the
      general role of susceptibility to PI in differences in higher cognitive function
      among older adults.

PMID- 18808253
TI  - Age-related deficits in reality monitoring of action memories.
AB  - The authors describe 3 theoretical accounts of age-related increases in falsely
      remembering that imagined actions were performed (A. K. Thomas & J. B. Bulevich,
      2006). To investigate these accounts and further explore age-related changes in
      reality monitoring of action memories, the authors used a new paradigm in which
      actions were (a) imagined only, (b) actually performed, or (c) both imagined and
      performed. Older adults were more likely than younger adults to misremember the
      source of imagined-only actions, with older adults more often specifying that the
      action was imagined and also that it was performed. For both age groups,
      illusions that the actions were only performed decreased as repetitions of the
      imagined-only events increased. These patterns suggest that both older and
      younger adults use qualitative characteristics when making reality-monitoring
      judgments and that repeated imagination produces richer records of both sensory
      details and cognitive operations. However, sensory information derived from
      imagination appears to be more similar to that derived from performance for older
      adults than for younger adults.

PMID- 18808254
TI  - Recognition memory measures yield disproportionate effects of aging on learning
      face-name associations.
AB  - No previous research has tested whether the specific age-related deficit in
      learning face-name associations that has been identified using recall tasks also
      occurs for recognition memory measures. Young and older participants saw pictures
      of unfamiliar people with a name and an occupation for each person, and were
      tested on a matching (in Experiment 1) or multiple-choice (in Experiment 2)
      recognition memory test. For both recognition measures, the pattern of effects
      was the same as that obtained using a recall measure: More face-occupation
      associations were remembered than face-name associations, young adults remembered
      more associated information than older adults overall, and older adults had
      disproportionately poorer memory for face-name associations. Findings implicate
      age-related difficulty in forming and retrieving the association between the face
      and the name as the primary cause of obtained deficits in previous name learning
      studies.

PMID- 18808255
TI  - Cognition, but not sensation, mediates age-related changes in the ability to
      monitor the environment.
AB  - The objective of the study was to determine which age-related changes in
      sensation and cognition are associated with age-related changes in the ability to
      monitor the environment. To that end, a proxy measure of the ability to monitor
      the environment (useful field of view, UFOV) and measures of sensation and
      cognition were collected from young adult (N = 61) and older adult subjects (N =
      79). Although UFOV performance was expected to be mediated primarily by cognition
      rather than by sensation, it was somewhat unexpected to find no reliable
      associations between UFOV and sensory functioning beyond those of age and
      cognition.

PMID- 18808256
TI  - Older adults prefer less choice than young adults.
AB  - Previous research has demonstrated that older adults prefer less autonomy and
      seek less information when making decisions on their own relative to young adults
      (for a review, see M. Mather, 2006). Would older adults also prefer fewer options
      from which to choose? The authors tested this hypothesis in the context of
      different decision domains. Participants completed a choice preferences survey in
      which they indicated their desired number of choices across 6 domains of health
      care and everyday decisions. The hypothesis was confirmed across all decision
      domains. The authors discuss implications from these results as they relate to
      theories of aging and health care policy.

PMID- 18808257
TI  - Age differences in forgiveness: the role of future time perspective.
AB  - This study investigated whether the age trend in forgiveness is partly
      attributable to age differences in time perspective. Eighty-nine younger and 91
      older adults were randomized into 3 experimental conditions: time-expanded, time
      limited, and neutral. They responded to hypothetical offensive scenarios and
      rated the degree to which they would forgive the perpetrator. Results showed that
      older adults were more forgiving than younger adults, but regardless of age,
      those in the time-limited condition were more forgiving than those in the time
      expanded or the neutral condition. An Age x Time perspective interaction showed
      that only in older adults did a time-expanded manipulation lead to lower
      forgiveness than the neutral condition.

PMID- 18808259
TI  - The moderator effect that wasn't there: statistical problems in ambivalence
      research.
AB  - Ambivalence researchers often collapse separate measures of positivity and
      negativity into a single numerical index of ambivalence and refer to it as
      objective, operative, or potential ambivalence. The authors argue that this
      univariate approach to ambivalence models undermines the validity of subsequent
      statistical analyses because it confounds the effects of the index and its
      components. To remedy this situation, they demonstrate how the assumptions
      underlying the indices derived from the conflicting reactions model and
      similarity-intensity model can be tested using a multivariate approach to
      ambivalence models. On the basis of computer simulations and reanalyses of
      published moderator effects, the authors show that the frequently reported
      moderating influence of ambivalence on attitude effects may be a statistical
      artifact resulting from unmodeled correlations of positivity and negativity with
      attitude and the dependent variable. On the basis of extensive power analyses,
      they conclude that it may be extremely difficult to detect moderator effects of
      ambivalence in observational data. Therefore, they encourage ambivalence
      researchers to take an experimental approach to study design and a multivariate
      approach to data analysis.

PMID- 18808258
TI  - Representations of the self in the near and distant future.
AB  - Seven studies provide evidence that representations of the self at a distant
      future time point are more abstract and structured than are representations of
      the self at a near-future time point and that distant-future behaviors are more
      strongly related to general self-conceptions. Distant-future self-representations
      incorporate broader, more superordinate identities than do near-future self
      representations (Study 1) and are characterized by less complexity (Study 2),
      more cross-situational consistency (Study 3), and a greater degree of
      schematicity (Study 4). Furthermore, people's behavioral predictions of their
      distant-future (vs. near-future) behavior are more strongly related to their
      general self-characteristics (Study 5), distant-future behaviors are seen as more
      self-expressive (Study 6), and distant-future behaviors that do not match up with
      acknowledged self-characteristics are more strongly rejected as reflections of
      the self (Study 7). Implications for understanding both the nature of the self
      concept and the way in which distance may influence a range of self-processes are
      discussed.

PMID- 18808260
TI  - Value revelations: disclosure is in the eye of the beholder.
AB  - In interpersonal interactions ranging from job interviews to romantic dates, it
      is common for people to tell each other about what they care about and value. Six
      experiments explored the general hypothesis that people view their disclosures
      about what they value as more revealing of themselves than do others. This effect
      is demonstrated across a variety of contexts, ranging from the brief and
      anonymous to the more in-depth and social. A source of it is explored in actors'
      feeling that their most important values are especially important to them.
      Studies suggest that this feeling involves actors' sense of the intensity with
      which they hold their values, as opposed to their beliefs about the uniqueness of
      those values. Studies also show that actors' tendency to view value disclosures
      as more revealing than do observers is somewhat specific to value disclosures-
      that is, actors do not view their relatively off-the-cuff responses (Study 4) or
      their disclosures of their nonvalues (Study 6) as more revealing. Implications of
      this research for self-other differences and for interpersonal intimacy are
      discussed.

PMID- 18808261
TI  - A new look at the consequences of attitude certainty: the amplification
      hypothesis.
AB  - It is well established that increasing attitude certainty makes attitudes more
      resistant to attack and more predictive of behavior. This finding has been
      interpreted as indicating that attitude certainty crystallizes attitudes, making
      them more durable and impactful. The current research challenges this
      crystallization hypothesis and proposes an amplification hypothesis, which
      suggests that instead of invariably strengthening an attitude, attitude certainty
      amplifies the dominant effect of the attitude on thought, judgment, and behavior.
      In 3 experiments, the authors test these competing hypotheses by comparing the
      effects of attitude certainty manipulations on univalent versus ambivalent
      attitudes. Across experiments, it is demonstrated that increasing attitude
      certainty strengthens attitudes (e.g., increases their resistance to persuasion)
      when attitudes are univalent but weakens attitudes (e.g., decreases their
      resistance to persuasion) when attitudes are ambivalent. These results are
      consistent with the amplification hypothesis.

PMID- 18808262
TI  - Cooperation in social dilemmas: free riding may be thwarted by second-order
      reward rather than by punishment.
AB  - Cooperation among nonrelatives can be puzzling because cooperation often involves
      incurring costs to confer benefits on unrelated others. Punishment of
      noncooperators can sustain otherwise fragile cooperation, but the provision of
      punishment suffers from a "second-order" free-riding problem because nonpunishers
      can free ride on the benefits from costly punishment provided by others. One
      suggested solution to this problem is second-order punishment of nonpunishers;
      more generally, the threat or promise of higher order sanctions might maintain
      the lower order sanctions that enforce cooperation in collective action problems.
      Here the authors report on 3 experiments testing people's willingness to provide
      second-order sanctions by having participants play a cooperative game with
      opportunities to punish and reward each other. The authors found that people
      supported those who rewarded cooperators either by rewarding them or by punishing
      nonrewarders, but people did not support those who punished noncooperators--they
      did not reward punishers or punish nonpunishers. Furthermore, people did not
      approve of punishers more than they did nonpunishers, even when nonpunishers were
      clearly unwilling to use sanctions to support cooperation. The results suggest
      that people will much more readily support positive sanctions than they will
      support negative sanctions.

PMID- 18808263
TI  - A test of the extended intergroup contact hypothesis: the mediating role of
      intergroup anxiety, perceived ingroup and outgroup norms, and inclusion of the
      outgroup in the self.
AB  - S. C. Wright, A. Aron, T. McLaughlin-Volpe, and S. A. Ropp (1997) proposed that
      the benefits associated with cross-group friendship might also stem from
      vicarious experiences of friendship. Extended contact was proposed to reduce
      prejudice by reducing intergroup anxiety, by generating perceptions of positive
      ingroup and outgroup norms regarding the other group, and through inclusion of
      the outgroup in the self. This article documents the first test of Wright et
      al.'s model, which used structural equation modeling among two independent
      samples in the context of South Asian-White relations in the United Kingdom.
      Supporting the model, all four variables mediated the relationship between
      extended contact and outgroup attitude, controlling for the effect of direct
      contact. A number of alternative models were ruled out, indicating that the four
      mediators operate concurrently rather than predicting one another.

PMID- 18808264
TI  - Let your preference be your guide? Preferences and choices are more tightly
      linked for North Americans than for Indians.
AB  - Using experimental paradigms from economics and social psychology, the authors
      examined the cross-cultural applicability of 3 widely held assumptions about
      preference and choice: People (a) recruit or construct preferences to make
      choices; (b) choose according to their preferences; and (c) are motivated to
      express their preferences in their choices. In 6 studies, they compared how
      middle-class North American and Indian participants choose among consumer
      products. Participants in both contexts construct nonrandom preferences at
      similar speeds. Those in Indian contexts, however, are slower to make choices,
      less likely to choose according to their personal preferences, and less motivated
      to express their preferences in their choices. The authors infer that the strong
      link between preferences and choices observed among North Americans is not a
      universal feature of human nature. Instead, this link reflects the disjoint model
      of agency, which prescribes that people should choose freely on the basis of
      their preferences. In contrast, Indian contexts reflect and promote a conjoint
      model of agency, according to which agency is responsive to the desires and
      expectations of important others and may require restraining one's preferences.

PMID- 18808265
TI  - When do the stigmatized stigmatize? The ironic effects of being accountable to
      (perceived) majority group prejudice-expression norms.
AB  - How do frequently stigmatized individuals feel about and respond to members of
      other potentially stigmatizable groups? Four studies demonstrated that
      perceptions of majority group norms regarding prejudice expression can shape how
      minority individuals respond to minority individuals from other groups. Study 1
      revealed that Black and White men and women have somewhat different perceptions
      of Whites' norms regarding prejudice expression. Study 2 manipulated whether
      evaluations of Native American job candidates were to remain private or to be
      made public to unfamiliar Whites upon whom the evaluators were dependent: Black
      men used a strategy of publicly (but not privately) denigrating the minority
      target to conform to presumed prejudice-expression norms. Study 3, in which the
      authors explicitly manipulated prejudice-expression norms, and Study 4, in which
      they manipulated audience race, further supported the role of such norms in
      eliciting public discrimination against minority group members by other minority
      group members. The desire to avoid being targeted for discrimination, in
      conjunction with the perception that the majority endorses discrimination,
      appears to increase the likelihood that the often-stigmatized will stigmatize
      others.

PMID- 18808266
TI  - "How long will I suffer?" versus "How long will you suffer?" A self-other effect
      in affective forecasting.
AB  - This research presents evidence that people predict longer durations of negative
      affect for others than for themselves. It is argued that this self-other effect
      is based on the asymmetric availability of knowledge about psychological
      strategies that reduce negative affective experiences. Specifically, because
      people have available knowledge about their own coping strategies, they use this
      information when making predictions about their affect. The lack of information
      about others' coping strategies leads to longer predictions of affect duration
      for others, creating the self-other effect. A series of studies demonstrated this
      self-other effect, its source, and its boundary conditions. Specifically, the
      self-other effect occurred for negative but not for positive events, it was
      stronger when participants predicted affect duration for unfamiliar others than
      when participants predicted affect duration for familiar others, and the impact
      of the self versus other focus on affective forecasts was mediated by the
      availability of knowledge about coping strategies. In addition, alternative
      explanations for the self-other effect were ruled out. The implications for
      biases in affective forecasting are discussed.

PMID- 18808268
TI  - Seeing race and seeming racist? Evaluating strategic colorblindness in social
      interaction.
AB  - One strategy practiced by many Whites to regulate the appearance of prejudice
      during social interaction is to avoid talking about race, or even acknowledging
      racial difference. Four experiments involving a dyadic task investigated
      antecedents and consequences of this tendency. Observed colorblindness was
      strategic in nature: Whites' acknowledgment of race was highly susceptible to
      normative pressure and most evident among individuals concerned with self
      presentational aspects of appearing biased (Study 1). However, this tendency was
      often counterproductive, as avoiding race during interracial interaction
      predicted negative nonverbal behavior (Study 1), a relationship mediated by
      decreased capacity to exert inhibitory control (Study 2). Two studies examining
      White and Black observers' impressions of colorblind behavior revealed divergent
      assessments of actors' prejudice in situations where race was clearly relevant
      (Study 3) but convergent assessments when race was less relevant (Study 4).
      Practical and theoretical implications for interracial interaction are
      considered.

PMID- 18808269
TI  - Not so ugly after all: when shame acts as a commitment device.
AB  - Most psychological theories and research on shame focus on the ugly aspects and
      negative consequences of this emotion. Theories on moral emotions, however,
      assume that shame acts as a commitment device motivating prosocial behavior. To
      solve this apparent paradox, the authors studied the effects of shame on
      prosocial behavior. Shame was hypothesized to motivate prosocial behavior when it
      was relevant for the decision at hand (endogenous). In contrast, shame that was
      not relevant for the decision at hand (exogenous) was hypothesized to have no
      such effects. Four experiments with three different shame inductions and two
      different measures of prosocial behavior confirmed that endogenous shame
      motivated prosocial behavior for proselfs but that exogenous shame did not. Shame
      is shown to have a clear interpersonal function in the sense that it acts as a
      commitment device.

PMID- 18808270
TI  - Me, myself, and us: salient self-threats and relational connections.
AB  - Guided by their own amoebic self theory (C. T. Burris & J. K. Rempel, 2004), in 6
      studies the authors explore the impact that involvement in an intimate
      relationship has on how a person appraises and responds to threat. They first
      show that people in relationship feel less constrained by their physical bodies
      compared with single people. In 3 subsequent studies involving physical size,
      blood/body donation, sexual activities, and responses to evil, they show that
      generalized sensitivity to bodily threat predicts self-protective reactions to
      specific physical threats among singles, but not among people in relationship,
      suggesting that intimate relationship involvement decreases the salience of the
      physical body. In the final pair of studies, they show that the salience of the
      physical body rebounds when people in relationship are primed, either
      subliminally or supraliminally, to think of themselves as distinct and separate
      from their partners. Thus, the present research shows how conceptualizing the
      self as "us" rather than "me" can transform an individual's response to the
      outside world, and highlights how physical cues in particular are affected by
      this process.

PMID- 18808271
TI  - Working memory capacity and self-regulatory behavior: toward an individual
      differences perspective on behavior determination by automatic versus controlled
      processes.
AB  - In the present research, the authors investigated how individual differences in
      working memory capacity moderate the relative influence of automatic versus
      controlled precursors on self-regulatory behavior. In 2 studies, on sexual
      interest behavior (Study 1) and the consumption of tempting food (Study 2),
      automatic attitudes toward the temptation of interest had a stronger influence on
      behavior for individuals who scored low rather than high in working memory
      capacity. Analogous results emerged in Study 3 on anger expression in a provoking
      situation when a measure of the automatic personality trait of angriness was
      employed. Conversely, controlled dispositions such as explicit attitudes (Study
      1) and self-regulatory goals (Studies 2 and 3) were more effective in guiding
      behavior for participants who scored high rather than low in working memory
      capacity. Taken together, these results demonstrate the importance of working
      memory capacity for everyday self-regulation and suggest an individual
      differences perspective on dual-process or dual-system theories of human
      behavior.

PMID- 18808272
TI  - Family metaphors and moral intuitions: how conservatives and liberals narrate
      their lives.
AB  - This research examines life-narrative interviews obtained from 128 highly
      religious and politically active adults to test differences between political
      conservatives and liberals on (a) implicit family metaphors (G. Lakoff, 2002) and
      (b) moral intuitions (J. Haidt & C. Joseph, 2004). Content analysis of 12 key
      scenes in life stories showed that conservatives, as predicted, tended to depict
      authority figures as strict enforcers of moral rules and to identify lessons in
      self-discipline. By contrast, liberals were more likely to identify lessons
      learned regarding empathy and openness, even though (contrary to prediction) they
      were no more likely than conservatives to describe nurturant authority figures.
      Analysis of extended discourse on the development of religious faith and personal
      morality showed that conservatives emphasized moral intuitions regarding respect
      for social hierarchy, allegiance to in-groups, and the purity or sanctity of the
      self, whereas liberals invested more significance in moral intuitions regarding
      harm and fairness. The results are discussed in terms of the recent upsurge of
      interest among psychologists in political ideology and the value of using life
      narrative methods and concepts to explore how politically active adults attempt
      to construct meaningful lives.

PMID- 18808273
TI  - Lay theory of race affects and moderates Asian Americans' responses toward
      American culture.
AB  - People may hold different understandings of race that might affect how they
      respond to the culture of groups deemed to be racially distinct. The present
      research tests how this process is moderated by the minority individual's lay
      theory of race. An essentialist lay theory of race (i.e., that race reflects deep
      seated, inalterable essence and is indicative of traits and ability) would orient
      racial minorities to rigidly adhere to their ethnic culture, whereas a social
      constructionist lay theory of race (i.e., that race is socially constructed,
      malleable, and arbitrary) would orient racial minorities to identify and
      cognitively assimilate toward the majority culture. To test these predictions,
      the authors conducted 4 studies with Asian American participants. The first 2
      studies examine the effect of one's lay theory of race on perceived racial
      differences and identification with American culture. The last 2 studies tested
      the moderating effect of lay theory of race on identification and assimilation
      toward the majority American culture after this culture had been primed. The
      results generally supported the prediction that the social constructionist theory
      was associated with more perceived similarity between Asians and Americans and
      more consistent identification and assimilation toward American culture, compared
      with the essentialist theory.

PMID- 18808274
TI  - Evaluating warning sound urgency with reaction times.
AB  - It is well-established that subjective judgments of perceived urgency of alarm
      sounds can be affected by acoustic parameters. In this study, the authors
      investigated an objective measurement, the reaction time (RT), to test the
      effectiveness of temporal parameters of sounds in the context of warning sounds.
      Three experiments were performed using a RT paradigm, with two different
      concurrent visuomotor tracking tasks simulating driving conditions. Experiments 1
      and 2 show that RT decreases as interonset interval (IOI) decreases, where IOI is
      defined as the time elapsed from the onset of one sound pulse to the onset of the
      next. Experiment 3 shows that temporal irregularity between pulses can capture a
      listener's attention. These findings lead to concrete recommendations: IOI can be
      used to modulate warning sound urgency; and temporal irregularity can provoke an
      arousal effect in listeners. The authors also argue that the RT paradigm provides
      a useful tool for clarifying some of the factors involved in alarm processing.

PMID- 18808275
TI  - Monopoly money: the effect of payment coupling and form on spending behavior.
AB  - This article examines consumer spending as a function of payment mode both when
      the modes differ in terms of payment coupling (association between purchase
      decision and actual parting of money) and physical form as well as when the modes
      differ only in terms of form. Study 1 demonstrates that consumers are willing to
      spend more when a credit card logo is present versus absent. Study 2 shows that
      the credit card effect can be attenuated when people estimate their expenses
      using a decomposition strategy (vs. a holistic one). Noting that credit card and
      cash payments differ in terms of payment coupling and form, Studies 3 and 4
      examine consumer spending when the payment mode differs only in physical form.
      Study 3 demonstrates that consumers spend more when they are spending scrip (a
      form of stored value certificate) versus cash of the same face value. Study 4
      shows that the difference in spending across payment modes (cash and gift
      certificates) is attenuated by altering the salience of parting with money
      through contextual manipulations of the differences between cash and gift
      certificates.

PMID- 18808276
TI  - Negative and positive pretrial publicity affect juror memory and decision making.
AB  - The experiment examined the effects of exposure to pretrial publicity (PTP) and
      delay on juror memory and decision-making. Mock jurors read news articles
      containing negative PTP, positive PTP, or unrelated articles. Five days later,
      they viewed a videotaped murder trial, after which they made decisions about
      guilt. Finally, all participants independently attributed specific information as
      having been presented during the trial or in the news articles. Half of the
      jurors rendered their verdicts and completed the source-memory test immediately
      after the trial, while the other half did so after a 2-day delay. Exposure to PTP
      significantly affected guilty verdicts, perceptions of defendant credibility,
      juror ratings of the prosecuting and defense attorneys, and misattributions of
      PTP as having been presented as trial evidence. Similar effects were obtained for
      negative and positive PTP. Delay significantly increased source-memory errors but
      did not influence guilt ratings. Defendant's credibility and juror ratings of
      prosecuting and defense attorneys significantly mediated the effect of PTP on
      guilt ratings.

PMID- 18808277
TI  - Effects of scenery, lighting, glideslope, and experience on timing the landing
      flare.
AB  - This study examined three visual strategies for timing the initiation of the
      landing flare based on perceptions of either: (a) a critical height above ground
      level; (b) a critical runway width angle (Psi); or (c) a critical time-to-contact
      (TTC) with the runway. Visual displays simulated landing approaches with trial-to
      trial variations in glideslope, lighting, and scene detail. Twenty-four
      participants (8 private pilots, 8 student pilots, and 8 nonpilots) were
      instructed to initiate the flare when they perceived that their TTC with the
      runway (30 m wide by 840 m long) had reached a critical value of 2 seconds. Our
      results demonstrated a significant effect of flight experience on flare timing
      accuracy and dominance of the height-based strategy over the runway-width-angle
      and TTC-based strategies.

PMID- 18808278
TI  - Food cravings consume limited cognitive resources.
AB  - Using Tiffany's (1990) cognitive model of drug use and craving as a theoretical
      basis, the present experiments investigated whether cravings for food expend
      limited cognitive resources. Cognitive performance was assessed by simple
      reaction time (Experiment 1) and an established measure of working memory
      capacity, the operation span task (Experiment 2). In each experiment, female
      undergraduate students were randomly assigned to a craving or control condition.
      Participants in the craving condition abstained from eating chocolate for 24
      hours prior to testing and performed the cognitive task in the presence of
      chocolate, a manipulation that successfully elicited chocolate cravings. In both
      experiments, there was no main effect of craving condition on cognition, but
      there was a significant interaction between condition and trait chocolate
      craving. In support of Tiffany's model, our results show that habitual food
      cravers direct limited cognitive resources to craving-related cues, at the cost
      of competing cognitive demands.

PMID- 18808279
TI  - "Don't know" responding to answerable and unanswerable questions during
      misleading and hypnotic interviews.
AB  - "Don't know" (DK) responses to interview questions are conceptually
      heterogeneous, and may represent uncertainty or clear statements about the
      contents of memory. A study examined the subjective intent of DK responses in
      relation to the objective status of information queried, in the context of memory
      distorting procedures. Participants viewed a video and responded to answerable
      and unanswerable questions phrased in misleading or nonmisleading formats, while
      hypnotized or not hypnotized. Subjective meanings of DK responses were queried,
      and a recognition measure assessed the contents of memory. Lower DK and accuracy
      rates were consistently associated with unanswerable and misleading questions.
      One-third of DK responses were statements that the information had no not
      presented. When these were recoded, accuracy estimates for answerable questions
      decreased and more so for hypnotized participants. These results demonstrate that
      DK responses convey different types of information, thus accuracy estimates in
      studies that permit DK responses may be misestimated. Robust risks associated
      with asking unanswerable questions and asking questions at all were observed.
      Implications for working with DK responses during interviews are discussed.

PMID- 18808280
TI  - Correcting memory improves accuracy of predicted task duration.
AB  - People are often inaccurate in predicting task duration. The memory bias
      explanation holds that this error is due to people having incorrect memories of
      how long previous tasks have taken, and these biased memories cause biased
      predictions. Therefore, the authors examined the effect on increasing predictive
      accuracy of correcting memory through supplying feedback for actual task
      duration. For Experiments 1 (paper-counting task) and 2 (essay-writing task),
      college students were supplied with duration information about their previous
      performance on a similar task before predicting task duration. For Experiment 3,
      participants were recruited at various locations, such as fast food restaurants
      and video arcades, and supplied with average task duration for others before
      predicting how long the task would take. In all 3 experiments, supplying feedback
      increased predictive accuracy. Overall, results indicate that, when predicting
      duration, people do well when they rely not on memory of past task duration but
      instead on measures of actual duration, whether their own or that of others.

PMID- 18808281
TI  - Improving the quality of facial composites using a holistic cognitive interview.
AB  - Witnesses to and victims of serious crime are normally asked to describe the
      appearance of a criminal suspect, using a Cognitive Interview (CI), and to
      construct a facial composite, a visual representation of the face. Research
      suggests that focusing on the global aspects of a face, as opposed to its facial
      features, facilitates recognition and improves composite quality; also, that the
      CI enables more effective use of a composite system. The current study evaluated
      a novel "holistic" Cognitive Interview (H-CI). This comprised a descriptive
      phase, using a CI, followed by a recognition-enhancing phase, involving the
      attribution of seven holistic properties. Participant-witnesses watched a video
      of a target, then 3 to 4 hours later received either a CI or an H-CI and
      constructed a single composite with a standard system, PRO-fit. Composites
      constructed after the H-CI were correctly named more than four times as often as
      those after the CI, attributable to an improvement in the quality of both the
      internal and external parts of the face. In police work, the H-CI offers the
      possibility of substantially improving the identification of criminal suspects.

PMID- 18808283
TI  - [Natural orifice transluminal endoscopic surgery (NOTES) - a view into the
      future?].

PMID- 18808282
TI  - External support for collaborative problem solving in a simulated
      provider/patient medication scheduling task.
AB  - Taking medication requires developing plans to accomplish the activity. This
      planning challenges older adults because of age-related cognitive limits and
      inadequate collaboration with health providers. The authors investigated whether
      an external aid (medtable) supports collaborative planning in the context of a
      simulated patient/provider task in which pairs of older adults worked together to
      create medication schedules. Experiment 1 compared pairs who used the medtable,
      blank paper (unstructured aid), or no aid to create schedules varying in
      complexity of medication constraints (number of medications and medication co
      occurrence restrictions) and patient constraints (available times during the day
      to take medication). Both aids increased problem-solving accuracy and efficiency
      (time per unit accuracy) compared to the no-aid condition, primarily for more
      complex schedules. However, benefits were similar for the two aids. In Experiment
      2, a redesigned medtable increased problem-solving accuracy and efficiency
      compared to blank paper. Both aids presumably supported problem solving by
      providing a jointly visible workspace for developing schedules. The medtable may
      be more effective because it externalizes constraints (relationships between
      medication and patient information), so that participants can more easily
      organize information.

PMID- 18808284
TI  - [Influence of surgeon specialization upon the results of colon cancer surgery.
      Usefulness of propensity scores].
AB  - INTRODUCTION: surgeon influence on colorectal cancer surgery outcomes has been
      repeatedly studied in the scientific literature, but conclusions have been
      contradictory. Here we study whether surgeon specialization is a determinant
      factor for outcome in these patients. The importance of propensity scores (PS) in
      surgical research is also studied. PATIENTS AND METHODS: a retrospective study
      was performed and medical records were reviewed for 236 patients who were
      intervened for colon cancer in Castellon General Hospital (Spain). Cases were
      divided into two groups (specialist and non-specialist surgeons), and both 5-year
      surveillance and disease free survival were compared. Comparisons were first made
      with no adjustments, and then subsequently using PS analysis. RESULTS: the
      initial (non-adjusted) analysis was clearly favourable for the specialist surgeon
      group (5-year surveillance, 64.3 vs. 79.3%, p = 0.028). After adjusting for PS no
      statistical significance was obtained. CONCLUSIONS: surgeon specialization had no
      significant impact on patient outcome after colon cancer surgery. Propensity
      score analysis is an important tool in the analysis of surgical non-randomized
      studies, particularly when events under scrutiny are rare.

PMID- 18808285
TI  - [Multidisciplinary approach to the treatment of rectal cancer: the benefits of
      neoadjuvant therapy].
AB  - OBJECTIVE: the aim of this study was to assess the impact of neoadjuvant
      treatment on rectal cancer following involvement of a multidisciplinary team
      (MDT). MATERIALS AND METHODS: between January 2000 and December 2005, 90 patients
      with rectal adenocarcinoma were evaluated by a MDT and operated on after
      receiving neoadjuvant treatment with radiochemotherapy (RTCT) -67% were men and
      33% were women, with a mean age of 65.04 years (21-83 years). Surgery was low
      anterior resection in 50% and abdominoperineal amputation in 42.2%. RESULTS: the
      rate of complications associated with neoadjuvant treatment was 54.4%, with
      gastrointestinal complications being most frequent. However, this toxicity was
      tolerated by most patients. It was severe in two cases (2.2%), leading to
      chemotherapy discontinuation. A histological analysis of specimens showed a
      complete pathologic response in 10 cases (11.1%) and a partial response
      (downstaging of T) in 32 cases (35.6%), hence overall response to neoadjuvant
      treatment was 46.6%. Postoperative complications included anastomotic leakage in
      8.3%, perineal wound complications in 34.2%, and urinary disease in 12.2%. The
      surgical mortality rate was 0%. Local recurrence occurred in 4.4%, and distant
      metastases were found in 22.2%. Both overall and disease-free survivals were 80
      and 64%, respectively. CONCLUSIONS: neoadjuvant treatment results in low local
      recurrence rates and optimal survival rates, with no increase in morbidity or
      mortality. A systematic evaluation by a MDT in the context of a clinical protocol
      offers better cure rates.

PMID- 18808286
TI  - [A clinical study of adult autoimmune hepatitis in Valencia, Spain].
AB  - OBJECTIVE: the clinical phenotype of autoimmune hepatitis (AIH) varies among
      geographical areas. The aim of this study is to determine the salient features of
      AIH in adult patients from the province of Valencia, Spain. MATERIAL AND METHODS:
      eighty-one patients with AIH attended to in eight acute-care hospitals between
      1994 and 2003. New patients diagnosed with AIH during year 2003 were evaluated
      prospectively. Data from patients currently attending follow-up visits and
      diagnosed before 2003 were collected retrospectively. RESULTS: a total of 94% of
      patients were females. Forty-three percent were asymptomatic, 27% had acute
      hepatitis, and 30% had chronic hepatitis. Type 1 AIH was diagnosed in 90% of
      cases. Type 2 AIH was more frequent in younger patients, and presented with an
      acute pattern. One third of patients had cirrhosis at onset. Patients with
      cirrhosis were older than 60 years more frequently. Immunosuppressants were given
      to 57 patients, with complete or partial remission in 87.7%. There were no
      significant differences in response to immunosuppression according to
      presentation pattern or AIH subtype. CONCLUSIONS: AIH in Valencia was
      predominantly diagnosed in asymptomatic women. Most cases were type 1, and in 25%
      of patients another autoimmune disease coexisted. At the time of diagnosis one
      third of patients had cirrhosis, particularly those over 60 years.

PMID- 18808287
TI  - [Preoperative workup to assess indication for laparoscopic treatment in
      gastroesophageal reflux disease].
AB  - INTRODUCTION AND OBJECTIVES: antireflux surgery performed by an experienced
      surgeon is a maintenance option for patients with well-documented
      gastroesophageal reflux disease (GERD). Well-documented GERD is difficult to
      find, as GERD is a multifactorial disease in which the gastroesophageal junction,
      with its special anatomical and functional components, is important. In order to
      examine patient preoperative workups, and their indication for surgical treatment
      in GERD, we retrospectively studied patients who underwent a laparoscopic
      antireflux procedure. METHODS: preoperative workups in patients from our health
      care area who underwent a laparoscopic antireflux procedure from December 1997 to
      February 2007 were retrospectively analyzed. Data related to epidemiological
      findings, symptoms, morphologic and functional evaluation, medical therapy, and
      indication for surgical treatment were recorded and statistically analyzed by
      means of a bivariate test. Differences were significant when the p value was
      equal to or less than 0.05. RESULTS: 100 patients (50 % female, 51.31 +/- 13.53
      years of age) underwent a laparoscopic antireflux surgery after 56.47 +/- 61.33
      months with symptoms. Ninety-five percent of patients had an anatomical
      abnormality. The pH monitoring test diagnosed three quarters of cases. The most
      frequent indication for GERD treatment was persistent or recurrent esophagitis
      despite adequate medical treatment (52 cases). CONCLUSIONS: based on our
      preoperative workup, as described, 100 percent of subjects were well documented
      and diagnosed with GERD (both non-erosive reflux disease and erosive reflux
      disease), and their indication for laparoscopic treatment was retrospectively
      assessed in 94% of cases.

PMID- 18808288
TI  - Transvaginal liver resection (NOTES) combined with minilaparoscopy.
AB  - OBJECTIVE: to report on the first liver resection performed on a human being by a
      transvaginal NOTES approach combined with minilaparoscopy. PATIENTS AND METHODS:
      a sixty-one-year-old woman with a history of Wertheim s hysterectomy for
      endometrial carcinoma 10 years ago, and malignant melanoma correctly treated in
      2006, had suspected segment-V liver metastasis near the gallbladder by CT-scan
      and MRI. The indication for a laparoscopic approach was made, and a combined
      transvaginal and minilaparoscopic resection was offered and accepted by the
      patient. The procedure was performed by a multidisciplinary team composed of
      surgeons and gastroenterologists. It involved creating a pneumoperitoneum by
      placing a Veres needle in the umbilical fundus, followed by the insertion of a 5
      mm trocar. A second, 3-mm trocar was placed in the right upper quadrant. A lot of
      pelvic adhesions were found in the major pelvis, and it was necessary to place a
      third, 5-mm trocar in the left abdominal side. It was employed only for the
      adhesions, not for liver resection. Adhesions were removed to reveal the minor
      pelvis and the vaginal fornix. A colpotomy was performed with a 12-mm trocar
      placed inside the vagina, which allowed the insertion of the videogastroscope as
      far as the liver hilum. RESULTS: liver resection (segment-V partial resection)
      and cholecystectomy were performed by using a combination of working tools
      inserted through the entry port for the minilaparoscopy and the videogastroscope.
      The en bloc resection was removed transvaginally through the videogastroscope.
      There were no postoperative complications, and the patient was discharged after
      48 hours. CONCLUSIONS: transvaginal liver resection is possible and safe when
      performed by a multidisciplinary team. Natural orifice transluminal endoscopic
      surgery (NOTES) is an emerging modality that seeks to be less invasive, better
      tolerated, and more respectful of esthetics. It will probably open the way for
      very important medical and technological innovations.

PMID- 18808289
TI  - [A cost-effectiveness study of hepatic venous pressure gradient measurement in
      the secondary prevention of variceal bleeding].
AB  - OBJECTIVE: variceal rebleeding is common following a first episode of hemorrhage
      in cirrhotic patients. The objective of this study was to determine the cost
      effectiveness of monitoring hepatic venous pressure gradient (HVPG) to guide
      secondary prophylaxis. METHODS: we created a Markov decision model to calculate
      cost-effectiveness for two strategies: Group 1: HVPG monitoring to decide
      treatment -when portal pressure was reduced by at least 20 percent or HVPG was
      less than 12 mmHg after beta-blocker administration, patients received beta
      blockers; when portal pressure did not meet these criteria therapy was endoscopic
      band ligation. Group 2: in this group there was no monitoring of HVPG. Patients
      with large varices received treatment with beta-blockers combined with EBL;
      patients with small varices received beta-blockers plus isosorbide mononitrate.
      RESULTS: there was no recurrent variceal bleeding in group 1 for good responders,
      and for 17% of poor responders. In group 2 a 25% rebleeding rate was detected in
      patients with small varices and 13% for those with big varices. Overall cost in
      group 1 was 14,100.49 euros, and 14,677.16 in group 2. CONCLUSIONS: HVPG
      measurement is cost-effective for the secondary prophylaxis of variceal bleeding.

PMID- 18808290
TI  - [Early diagnosis of primary liver cancer: imaging versus genetics].
AB  - Early diagnosis of hepatocellular carcinoma (HCC) in nodules smaller than 2 cm
      detected by screening ultrasounds becomes essential given that, at that stage, no
      vascular invasion is usually detected and treatment is associated with a high
      rate of long-term survival. Improvements in imaging techniques in the last few
      years have allowed a conclusive diagnosis of HCC in these small nodules without
      invasive procedures. However, a conclusive diagnosis of HCC by imaging is not
      always possible and, in more than half of cases, biopsy is needed. On the other
      hand, histological confirmation of HCC in such tiny nodules is very complex, and
      in most cases impossible because of the limited sample obtained. In addition,
      serum tumor markers currently available show low accuracy and are useless for
      early diagnosis. Progress in the knowledge of molecular mechanisms associated
      with malignant transformation will allow the use of new techniques that will
      facilitate diagnosis for HCC in very early stages.

PMID- 18808291
TI  - [Jaundice from choledocholithiasis diagnosed using plain abdominal radiography].

PMID- 18808292
TI  - [Biliary ileus in a patient with advanced age].

PMID- 18808293
TI  - Recurrence of hepatocellular carcinoma after liver transplantation presenting as
      anastomotic biliary stricture.
AB  - A 52-year-old man visited our hospital complaining of anorexia and fatigue two
      months after receiving orthotopic liver transplantation for hepatocellular
      carcinoma. A laboratory investigation demonstrated a clinical picture of
      obstructive jaundice. T-tube cholangiography showed biliary stricture over the
      anastomotic site. Percutaneous transluminal balloon dilatation and stenting was
      attempted but failed. Magnetic resonance cholangiography showed possible tumor
      recurrence over the site of the anastomotic biliary stricture. A biopsy sample
      was obtained via ultrasound-guided aspiration and histopathological study
      revealed inflammatory and fibrotic changes. With high suspicion of recurrence of
      the hepatocellular carcinoma, surgical exploration was performed and an
      intraoperative frozen section proved the recurrence. We thus diagnosed this case
      as a recurrence of hepatocellular carcinoma after liver transplantation. To our
      knowledge, there have been no previous reports of early tumor recurrence after
      liver transplantation being the cause of an anastomotic biliary stricture.

PMID- 18808294
TI  - [Incarcerated Morgagni's hernia in an adult].

PMID- 18808295
TI  - Function association of enhanced expressed genes between Opisthorchis viverrini
      and non Opisthorchis viverrini-related cholangiocarcinoma.

PMID- 18808296
TI  - [Rectal metastasis of lobular breast carcinoma].

PMID- 18808297
TI  - [Gastrointestinal bleeding due to duodenal lipoma].

PMID- 18808299
TI  - [Reply: iatrogenic injury of an aberrant, independent, right hepatic duct (V-VIII
      segments). Diagnostic and therapeutic difficulties].

PMID- 18808300
TI  - Life after placement: experiences of older rural caregivers after placing a
      family member into residential care.
AB  - INTRODUCTION: The community care philosophy in Australia has led to a number of
      older people remaining in their own homes, dependant on others for the majority
      of their care needs. A small number of older people being cared for by a family
      member or friend will move into residential aged care facilities for full-time
      care. This article describes a qualitative study that explored the meanings that
      older rural Australian caregivers gave to their day-to-day lives after their care
      receiver had entered full-time residential aged care. METHODS: Semi-structured
      interviews with seven older caregivers were conducted to gain understandings
      about their 'life after placement'. Thematic analysis was employed to identify
      common themes. Quality of life concepts provided the boundaries to the research
      questions. RESULTS: The sample included four men and three women. In the study,
      the men reported spending more time continuing their carer role, while the women
      reported being more focussed on reconnecting with the community. Both men and
      women reported that their own health was a major constraint in being able to
      maintain these two tasks. The findings mirrored those of similar studies with one
      notable exception: this study highlighted the meanings that caregivers gave to
      their lives after placement in a more holistic way, as opposed to focussing on
      caregivers in relation to the residential aged care facility context alone.
      CONCLUSION: This study demonstrated that there are differences found in relation
      to gender and tasks after in-home caring roles have ended. Worry about loss of
      driving ability was a major concern in the caregivers' lives. The experiences of
      the caregivers in this study give a better understanding of what life is like for
      caregivers after in-home caring has ceased. Understanding of 'life after
      placement' expands our knowledge about carers and the role of carer. The findings
      suggest a need for funding and programs for caregivers after their in-home carer
      role has ended to assist caregivers (particularly men) in reconnecting with
      people and activities outside their immediate family. The findings may direct
      rural community development workers to appreciate the challenges that older rural
      caregivers face when their in-home caring role ends and visiting and socializing
      is dependant on their ability to drive. This study also offers a perspective for
      residential aged care staff to consider as they work with families placing an
      older family member into full-time care. If aged care staff recognise the value
      of the continuing caring role of the caregiver and integrate them into the care
      plan, enhanced positive outcomes could transpire for both caregiver and care
      recipient.

PMID- 18808301
TI  - Heterotopic pregnancy: a clinical case report from rural Nigeria.
AB  - Heterotopic pregnancy (HP) is the co-existence of intrauterine and ectopic
      pregnancies; it is said to be rare. We report the case of a 22 year old woman
      with HP after unsuccessful attempts at abortion. This report illustrates the
      treatment difficulties encountered in a delayed presentation, and the nature HP
      is assuming in rural practice. It also highlights the role of family physicians
      in reducing maternal mortality in resource-limited settings.

PMID- 18808302
TI  - Character convergence under competition for nutritionally essential resources.
AB  - Resource competition is thought to drive divergence in resource use traits
      (character displacement) by generating selection favoring individuals able to use
      resources unavailable to others. However, this picture assumes nutritionally
      substitutable resources (e.g., different prey species). When species compete for
      nutritionally essential resources (e.g., different nutrients), theory predicts
      that selection drives character convergence. We used models of two species
      competing for two essential resources to address several issues not considered by
      existing theory. The models incorporated either slow evolutionary change in
      resource use traits or fast physiological or behavioral change. We report four
      major results. First, competition always generates character convergence, but
      differences in resource requirements prevent competitors from evolving identical
      resource use traits. Second, character convergence promotes coexistence.
      Competing species always attain resource use traits that allow coexistence, and
      adaptive trait change stabilizes the ecological equilibrium. In contrast,
      adaptation in allopatry never preadapts species to coexist in sympatry. Third,
      feedbacks between ecological dynamics and trait dynamics lead to surprising
      dynamical trajectories such as transient divergence in resource use traits
      followed by subsequent convergence. Fourth, under sufficiently slow trait change,
      ecological dynamics often drive one of the competitors to near extinction, which
      would prevent realization of long-term character convergence in practice.

PMID- 18808303
TI  - The many faces of erythropoietin: from erythropoiesis to a rational
      neuroprotective strategy.

PMID- 18808304
TI  - Therapeutic potential of inhaled p38 mitogen-activated protein kinase inhibitors
      for inflammatory pulmonary diseases.
AB  - BACKGROUND: Over the past two decades, p38 MAPK (mitogen-activated protein
      kinase) has been the subject of intense multidisciplinary research. p38 MAPK
      inhibitors have been shown to be efficacious in several disease models, including
      rheumatoid arthritis, psoriasis, Crohn's disease, and stroke. Recent studies
      support a role for p38 MAPK in the development, maintenance, and/or exacerbation
      of a number of pulmonary diseases, such as asthma, cystic fibrosis, idiopathic
      pulmonary fibrosis, and chronic obstructive pulmonary disease (COPD). OBJECTIVE:
      Many previous attempts to develop p38 MAPK inhibitors have failed as a result of
      unacceptable safety profiles. These toxicities have been varied and are believed
      to derive from different off-target effects. METHOD: The above concerns can be
      overcome by delivering the compound locally to minimize whole-body burden,
      resulting in low exposure to the gastrointestinal, liver, and CNS. This review
      discusses the role of p38 MAPK in various inflammatory diseases, followed by the
      toxicity concerns associated with p38 MAPK inhibition. It also highlights the
      possible beneficial effect of delivering drugs via the inhalation route.
      CONCLUSION: We present proof-of-principle confirming the therapeutic potential of
      inhaled p38 inhibitors for asthma and other inflammatory pulmonary diseases.

PMID- 18808305
TI  - Benznidazole and Chagas disease: can an old drug be the answer to an old problem?
AB  - BACKGROUND: Chagas disease is a significant public health problem in the
      Americas, despite efforts to decrease the number of new cases since 1990.
      Etiologic treatment of the disease's chronic phase is still controversial.
      OBJECTIVE: We reviewed the strongest studies to evaluate the drugs used in the
      acute and chronic disease phases, with emphasis on benznidazole. METHODS: A
      Medline search using the keywords 'Chagas disease' and 'treatment,' with no date
      limitations, was performed. RESULTS: Study methods in completed trials varied
      greatly, with none being a randomized, double-blind, placebo-controlled study.
      The only trial using these methods is still ongoing. The treatment in acute phase
      is the major indication, but during chronic phase doubts still remain.
      CONCLUSION: Only patients in the acute phase of Chagas disease (whatever their
      age; including children and adolescents) who are treated have good outcomes,
      although the criteria defining 'cure' remain controversial.

PMID- 18808306
TI  - Statins: under investigation for increasing bone mineral density and augmenting
      fracture healing.
AB  - BACKGROUND: Statins are 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitors
      and have been shown to possess anti-lipidaemic properties effective in lowering
      cholesterol. Recent evidence has suggested beneficial pleiotropic effects,
      including that of fracture healing, alongside its widely accepted ability to
      reduce the incidence of cardiovascular disease. OBJECTIVES: A comprehensive
      review of the recent literature on the effect of statins on bone mineral density
      and fracture healing. METHODS: Medline/Ovid and EMBASE search and manual search
      of bibliography of key papers, on the effects of statins on bone metabolism
      including in vitro and in vivo studies, as well as clinical trials on the effects
      of statins on bone mineral density and fracture risk. RESULTS/CONCLUSIONS: There
      is robust in vitro and in vivo evidence to suggest the anabolic effects of
      statins on bone metabolism. Although evidence in patients with osteoporosis is
      conflicting, several studies have shown that the use of statins is associated
      with increases in bone mass density and reduction in fracture risk. Conflicting
      studies identified may be due to different routes of administration, types of
      statins employed and low doses used. Taken together, there is strong evidence to
      suggest that statins have beneficial effects on fracture healing that would
      support further clinical trials investigating such properties.

PMID- 18808307
TI  - PPAR-beta/delta agonists for Type 2 diabetes and dyslipidemia: an adopted orphan
      still looking for a home.
AB  - BACKGROUND: The identification of small molecule agonists for the nuclear
      receptor peroxisome proliferator-activated receptor beta/delta (PPAR-beta/delta,
      NR1C2) has enabled the characterization of this receptor's functions in
      preclinical models. Subsequently, a number of small molecule agonists of PPAR
      beta/delta have been progressed into clinical trials. OBJECTIVE: This review will
      examine the major preclinical findings that underpin the hypothesis that PPAR
      beta/delta agonists may be beneficial in treating dyslipidemia and Type 2
      diabetes, as well as emerging clinical data with a variety of PPAR-beta/delta
      agonists. METHODS: The literature concerning preclinical experiments that combine
      in vivo and in vitro mechanistic studies are reviewed and compared with the
      results of the early clinical trials. CONCLUSIONS: Thus far, the activities of
      the agonists seen in the clinic are broadly similar to those seen in preclinical
      models. However, it is still not known if PPAR-beta/delta agonists will truly be
      differentiated enough from current treatments to justify their use in treating
      dyslipidemia or Type 2 diabetes. Major challenges for the development of PPAR
      beta/delta agonists exist and the path forward is as yet undefined.

PMID- 18808308
TI  - Nicotinic receptor partial agonists as novel compounds for the treatment of
      smoking cessation.
AB  - Nicotine addiction and the neurobiological mechanisms explaining nicotine
      reinforcement, withdrawal, and relapse involve alpha4beta2 nicotinic
      acetylcholine receptors (nAChRs). This review updates readers on the preclinical
      and clinical pharmacology, as well as the therapeutic efficacy and safety of
      cytisine and varenicline, the two partial agonists of nAChRs for smoking
      cessation. Cytisine has been used for several decades; yet despite its surprising
      popularity in some parts of the world, it has been absent from almost all
      existing reviews of smoking cessation drugs. If safe and sufficiently
      efficacious, an obvious advantage would be its low cost, which could make
      cytisine an attractive treatment available to millions of smokers. Varenicline
      was recently introduced to the drug market and has been found to be more
      efficacious than existing treatments. Very encouraging results of early human
      trials and strong theoretical background for their use make the nAChRs partial
      agonists a promising alternative for currently available antismoking treatments.

PMID- 18808309
TI  - Investigational drugs for diabetic nephropathy.
AB  - BACKGROUND: Diabetic nephropathy is one of the main causes of end-stage renal
      disease (ESRD) and is associated with elevated cardiovascular morbidity and
      mortality. OBJECTIVE: Current renoprotective treatments for diabetic nephropathy
      include strict glycemic and optimal blood pressure control,
      proteinuria/albuminuria reduction and the use of renin-angiotensin-aldosterone
      system (RAAS) blocking agents. However, the renoprotection provided by these
      treatments is only partial, calling for more effective approaches. METHODS: This
      review examines emerging strategies for the treatment of diabetic nephropathy,
      including aggressive RAAS blockade, statins, glitazones, ruboxistaurin, and other
      promising agents. RESULTS/CONCLUSIONS: In diabetic patients with overt
      nephropathy, multipharmacological interventions represent a promising way to
      prevent progression to ESRD. Results of ongoing trials are needed to establish
      whether the current standard of care of diabetic nephropathy might be improved
      with these new strategies.

PMID- 18808310
TI  - Novel drugs for renal cell carcinoma.
AB  - BACKGROUND: Treatment of advanced renal cell carcinoma (RCC) has undergone
      significant changes over the past 3 years after a long period of relative
      stagnation. A better understanding of the biology of the tumor led to the
      discovery of molecular targeted therapies resulting in significant improvement in
      outcome for this common malignancy. OBJECTIVES: A review of new drugs, both
      established and investigational, at present used in the treatment of RCC is
      provided in this article. METHODS: A comprehensive free-text search of all
      available published literature including but not limited to, Medline, Scopus,
      American Society of Clinical Oncology presentations, National Comprehensive
      Cancer Network guidelines and information available through other national and
      international scientific organizations was carried out during the preparation of
      this manuscript. CONCLUSIONS: Targeted therapy in RCC is a prime example of
      successful translational research. Continuing clinical and preclinical research
      in drug development holds promise for further advances in this area.

PMID- 18808311
TI  - EGFR inhibition as a therapy for head and neck squamous cell carcinoma.
AB  - BACKGROUND: Improved understanding of disease biology of head and neck squamous
      cell carcinoma (HNSCC) with nearly universal expression of EGFR has led to the
      introduction of targeted therapies to interrupt signalling of this negative
      prognostic marker. OBJECTIVE: We performed a literature review on the mechanisms
      and efficacy of anti-EGFR antibodies and EGFR tyrosine kinase inhibitors in
      patients with locally advanced or recurrent/metastatic HNSCC. RESULTS/CONCLUSION:
      Clinical trials in HNSCC have administered EGFR directed drugs as single agents,
      in combination with chemotherapy or radiotherapy and demonstrated a good safety
      profile with antitumour activity in a subgroup of patients. The biology of
      responsiveness is still unclear, although there is growing evidence of an
      association of skin toxicity or presence of shorter EGFR intron 1 cytosine
      adenine repeats with positive outcome.

PMID- 18808312
TI  - Glycolytic enzyme inhibitors in cancer treatment.
AB  - BACKGROUND: The radio- and chemotherapeutics currently used for the treatment of
      cancer are widely known to be characterized by a low therapeutic index. An
      interesting approach to overcoming some of the limits of these techniques is the
      exploitation of the so-called Warburg effect, which typically characterizes
      neoplastic cells. Interestingly, this feature has already been utilized with good
      results, but only for diagnostic purposes (PET and SPECT). From a pharmacological
      point of view, drugs able to perturb cancer cell metabolism, specifically at the
      level of glycolysis, may display interesting therapeutic activities in cancer.
      OBJECTIVE: The pharmacological actions of these glycolytic enzyme inhibitors,
      based primarily on ATP depletion, could include: i) amelioration of drug
      selectivity by exploiting the particular glycolysis addiction of cancer cell; ii)
      inhibition of energetic and anabolic processes; iii) reduction of hypoxia-linked
      cancer-cell resistance; iv) reduction of ATP-dependent multi-drug resistance; and
      v) cytotoxic synergism with conventional cancer treatments. CONCLUSION: Several
      glycolytic inhibitors are currently in preclinical and clinical development.
      Their clinical value as anticancer agents, above all in terms of therapeutic
      index, strictly depends on a careful reevaluation of the pathophyiological role
      of the unique metabolism of cancer cells in general and of Warburg effect in
      particular.

PMID- 18808313
TI  - ASA404: update on drug development.
AB  - BACKGROUND: Interrupting tumour blood flow and delivery of nutrients to cause
      tumour death is the aim of antiangiogenic and vascular disrupting agents (VDAs).
      ASA404 is the first VDA to enter Phase III trials. OBJECTIVE: We review the
      preclinical and clinical data on this interesting agent and consider its place in
      modern therapeutics. METHODS: PubMed database was searched for 'ASA404',
      'AS1404', 'DMXAA', 'vascular disrupting agents', 'ASA404 clinical trials',
      'AS1404 clinical trials', 'DMXAA clinical trials'. RESULTS/CONCLUSIONS: ASA404 is
      a tumour VDA that is well tolerated and has shown promise in the treatment of
      NSCLC in combination with paclitaxel and carboplatin. A confirmatory Phase III
      trial is currently ongoing.

PMID- 18808314
TI  - Ertumaxomab: a trifunctional antibody for breast cancer treatment.
AB  - Ertumaxomab is an intact bispecific antibody targeting HER2/neu and CD3 with
      preferential binding to activating Fcgamma type I/III-receptors, resulting in the
      formation of a tri-cell complex among tumour cell, T cell and accessory cell.
      Recently, the antibody demonstrated antitumour efficacy against HER2/neu low
      expressing tumours resistant to trastuzumab. Data from a completed Phase I study
      in metastatic breast cancer patients indicates strong immune responses. Owing to
      efficient tumour cell destruction by humoral and T-cell-dependent mechanisms,
      differing from conventional HER2/neu directed treatments, and a potential for
      long-lasting antitumour immunoreactivity, ertumaxomab is at present investigated
      within Phase II studies enrolling metastatic breast cancer patients even without
      HER2/neu gene amplification.

PMID- 18808315
TI  - Janumet: a combination product suitable for use in patients with Type 2 diabetes.
AB  - Inhibition of the enzyme dipeptidyl peptidase-4 represents the latest
      pharmacologic intervention to become available to assist patients with Type 2
      diabetes to achieve glycemic control. A combination tablet of sitagliptin
      (Januvia) and metformin HCl (Glucophage) is now available from Merck (Janumet).
      The FDA has approved this drug for use in patients who are not adequately
      controlled by taking either sitagliptin or metformin HCl alone or for patients
      who are at present taking both simultaneously. Sitagliptin has been shown to be
      safe and effective at 100 mg daily doses. When given in combination with
      metformin the effect on glycemic control is thought to be complementary and
      possibly additive.

PMID- 18808316
TI  - Prolonged-release melatonin for the treatment of insomnia in patients over 55
      years.
AB  - BACKGROUND: Clinical data show that poor quality, rather than quantity, of sleep
      corresponds negatively to measures of health, well-being and satisfaction with
      life. However, until now treatment of insomnia has primarily targeted quantity of
      sleep. PR (prolonged release)-melatonin offers a new treatment option in
      insomnia. OBJECTIVES: To provide an overview of PR-melatonin, the first melatonin
      receptor agonist to be granted marketing authorisation in Europe as monotherapy
      for the treatment of primary insomnia in patients aged > 55 years. METHODS:
      Review data published in peer review journals and the EMEA (European Medicines
      Agency) website. RESULTS/CONCLUSION: PR-melatonin significantly improves morning
      alertness and quality of sleep compared with placebo. There are no safety
      concerns.

PMID- 18808317
TI  - Expert opinion on tilarginine in the treatment of shock.
AB  - Tilarginine is L-N-monomethyl arginine (L-NMMA) or N(G)-monomethyl-L-arginine
      HCL, a non-selective inhibitor of nitric oxide synthase (NOS), which has been
      studied in the treatment of septic shock and cardiogenic shock complicating
      myocardial infarction. Despite strong evidence that excessive nitric oxide (NO)
      production plays a pivotal role in the pathogenesis of septic shock and may
      contribute to the pathogenesis of cardiogenic shock complicating myocardial
      infarction, outcome studies in these two disorders have proved disappointing. L
      NMMA therapy was associated with an excess mortality, particularly at doses > 5
      mg/(kg h), in septic shock whereas the effects of a lower dose (1 mg/(kg h)) in
      cardiogenic shock complicating myocardial infarction were neutral. The excess
      mortality in patients with septic shock was almost certainly the result of
      unfavourable haemodynamic changes induced by L-NMMA (decreased cardiac output,
      increased pulmonary vascular resistance and reduced tissue oxygen delivery)
      whereas the lack of benefit in patients with cardiogenic shock complicating
      myocardial infarction may have been because the dose of L-NMMA was too low.
      Further studies of L-NMMA at doses < 5 mg/(kg h) in conjunction with inotrope
      support may produce more beneficial results. Conversely, the use of a selective
      inducible NOS inhibitor to reduce the pathological effects of excessive NO
      production although leaving the beneficial effects of vascular NO production by
      endothelial NOS unaltered may prove to be of value.

PMID- 18808318
TI  - LB80380: a promising new drug for the treatment of chronic hepatitis B.
AB  - Hepatitis B virus is a significant cause of liver cirrhosis and hepatocellular
      carcinoma in patients with chronic infection. Higher levels of viral load are
      associated with increased risk of developing liver-related complications. The
      current available oral therapies suppress viral replication through their action
      on the hepatitis B virus polymerase. As treatment with oral nucleoside/nucleotide
      analogues is associated with the development of drug-resistant mutations, there
      is continuing research for newer and more potent antiviral agents to reduce the
      chance of drug resistance. LB80380, a prodrug, is an oral nucleotide analogue
      that inhibits viral replication by incorporation into the viral DNA. Antiviral
      activity against wild-type virus and virus with drug-resistant mutations was
      demonstrated in Phase II trials, with significant reduction of viral load in
      patients treated with LB80380. LB80380 was also shown to be safe and well
      tolerated.

PMID- 18808319
TI  - JTT-705: is there still future for a CETP inhibitor after torcetrapib?
AB  - BACKGROUND: Despite reduction in low-density lipoprotein cholesterol, there is
      still a considerable amount of residual atherosclerosis-related disease.
      Epidemiological and pathophysiological data strongly favour increasing plasma
      high-density lipoprotein (HDL) cholesterol levels as antiatherogenic therapy, for
      example with cholesteryl ester transfer inhibition (CETP). However, negative
      Phase III studies on clinical end points with the CETP inhibitor torcetrapib
      challenge the future perspectives of other CETP inhibitors such as JTT-705.
      OBJECTIVE: Is there potential for CETP inhibition with JTT-705 after
      torcetrapib's collapse? METHODS: Search of articles in Pubmed citing JTT-705,
      torcetrapib and anacetrapib, or citing effects of pharmacological HDL-cholesterol
      raising or CETP inhibition. RESULTS/CONCLUSION: There is possibly a future for
      HDL-cholesterol raising therapies. Phase III clinical studies with either JTT-705
      or anacetrapib will determine whether CETP inhibition is beneficial.

PMID- 18808320
TI  - Treatment of hyperlipidaemia with fenofibrate and related fibrates.
AB  - BACKGROUND: Fenofibrate is the most widely used fibrate. Its efficacy and
      tolerability in the treatment of hypertriglyceridaemia and combined
      hyperlipidaemia have been demonstrated in several clinical trials. OBJECTIVE: To
      review the pharmacology, lipid-lowering and extra-lipid effects of fenofibrate
      and to preview ABT-335, an investigational new fenofibric acid molecule. RESULTS:
      The effects of fenofibrate are mediated through the active metabolite fenofibric
      acid, and are described in detail in the paper. ABT-335 is a salt of fenofibric
      acid and, unlike fenofibrate, does not require first pass metabolism to the
      active moiety. ABT-335 is being developed for combination use with statins, and
      has recently completed three large Phase III randomised controlled trials in
      which the efficacy and safety of ABT-335 in combination with the three most
      commonly prescribed statins, atorvastatin, simvastatin and rosuvastatin, was
      evaluated in patients with mixed dyslipidaemia. CONCLUSION: ABT-335 in
      combination with statins may provide a safe and efficacious treatment modality
      that enables achievement of several therapeutic goals in patients with mixed
      dyslipidaemia who have high cardiovascular risk.

PMID- 18808321
TI  - The many faces of erythropoietin: from erythropoiesis to a rational
      neuroprotective strategy--correspondence.

PMID- 18808324
TI  - Statins in endothelial signaling and activation.
AB  - The beneficial effects of statins, the most widely prescribed class of drugs in
      the world, are now recognized to extend well beyond their lipid-lowering
      properties. Through a combination of both distinct and interdependent effects on
      endothelial cell (EC) Rho GTPase regulation, NAPDH oxidase activity, NO
      bioavailability, and differential gene expression, statins confer significant
      protection of the vasculature. Abundant in vitro data, in addition to myriad
      reports relying on a range of animal models, now firmly support the idea that
      these drugs may serve as novel and effective therapeutic agents in a variety of
      disease states characterized by vascular dysfunction.

PMID- 18808323
TI  - Hug tightly and say goodbye: role of endothelial ICAM-1 in leukocyte
      transmigration.
AB  - Stable adhesion of leukocytes to endothelium is crucial for transendothelial
      migration (TEM) of leukocytes evoked during inflammatory responses, immune
      surveillance, and homing and mobilization of hematopoietic progenitor cells. The
      basis of stable adhesion involves expression of intercellular adhesion molecule-1
      (ICAM-1), an inducible endothelial adhesive protein that serves as a counter
      receptor for beta(2)-integrins on leukocytes. Interaction of ICAM-1 with beta(2)
      integrins enables leukocytes to adhere firmly to the vascular endothelium and
      subsequently, to migrate across the endothelial barrier. The emerging paradigm is
      that ICAM-1, in addition to firmly capturing leukocytes, triggers intracellular
      signaling events that may contribute to active participation of the endothelium
      in facilitating the TEM of adherent leukocytes. The nature, duration, and
      intensity of ICAM-1-dependent signaling events may contribute to the
      determination of the route (paracellular vs. transcellular) of leukocyte passage;
      these aspects of ICAM-1 signaling may in turn be influenced by density and
      distribution of ICAM-1 on the endothelial cell surface, the source of endothelial
      cells it is present on, and the type of leukocytes with which it is engaged. This
      review summarizes our current understanding of the "ICAM-1 paradigm" of TEM with
      an emphasis on the signaling events mediating ICAM-1 expression and activated by
      ICAM-1 engagement in endothelial cells.

PMID- 18808325
TI  - A conserved role for Hox paralog group 4 in regulation of hematopoietic
      progenitors.
AB  - Regulatory circuits that control stem cell fate decisions can be identified and
      understood by manipulating individual regulatory elements genetically. While
      impractical in the rare somatic stem cells of primary tissue, this approach is
      feasible in embryonic stem cells differentiated in vitro into the somatic stem
      cell type of interest. We present an improved highly efficient targeting system
      allowing genes to be integrated into a predetermined, doxycycline-inducible
      locus, and corresponding inducible embryonic stem cell lines to be generated
      rapidly. We apply this system to evaluate a key hematopoietic progenitor cell
      regulatory element, HoxB4, and its mammalian paralogs, whose effects have not yet
      been tested in this context. We show that all Hox paralog group 4 members, A4,
      B4, C4, and D4, have similar effects on hematopoietic stem and progenitor self
      renewal in vitro, and thus classify Hox paralog group 4 as promoting self
      renewal. Each paralog group 4 member both promotes proliferation and inhibits
      differentiation, enabling the exponential expansion of hematopoietic progenitors
      from the c-kit(+)/CD41(+) cell fraction of day 6 murine embryoid bodies. By
      evaluating a set of deletion mutants we show that sequences in addition to the
      homeodomain and hexapeptide motif are required for this activity. These results
      highlight the utility of this expression system to perform functional and
      structural analyses of genetic regulators of cell fate decisions.

PMID- 18808326
TI  - Mechanisms of muscle degeneration, regeneration, and repair in the muscular
      dystrophies.
AB  - To withstand the rigors of contraction, muscle fibers have specialized protein
      complexes that buffer against mechanical stress and a multifaceted repair system
      that is rapidly activated after injury. Genetic studies first identified the
      mechanosensory signaling network that connects the structural elements of muscle
      and, more recently, have identified repair elements of muscle. Defects in the
      genes encoding the components of these systems lead to muscular dystrophy, a
      family of genetic disorders characterized by progressive muscle wasting. Although
      the age of onset, affected muscles, and severity vary considerably, all muscular
      dystrophies are characterized by muscle necrosis that overtakes the regenerative
      capacity of muscle. The resulting replacement of muscle by fatty and fibrous
      tissue leaves muscle increasingly weak and nonfunctional. This review discusses
      the cellular mechanisms that are primarily and secondarily disrupted in muscular
      dystrophy, focusing on membrane degeneration, muscle regeneration, and the repair
      of muscle.

PMID- 18808327
TI  - Stem cells, self-renewal, and differentiation in the intestinal epithelium.
AB  - The mammalian intestine is covered by a single layer of epithelial cells that is
      renewed every 4-5 days. This high cell turnover makes it a very attractive and
      comprehensive adult organ system for the study of cell proliferation and
      differentiation. The intestine is composed of proliferative crypts, which contain
      intestinal stem cells, and villi, which contain differentiated specialized cell
      types. Through the recent identification of Lgr5, an intestinal stem cell marker,
      it is now possible to visualize stem cells and study their behavior and
      differentiation in a much broader context. In this review we describe the
      identification of intestinal stem cells. We also discuss genetic studies that
      have helped to elucidate those signals important for progenitor cells to
      differentiate into one of the specialized intestinal epithelial cell types. These
      studies describe a genetic hierarchy responsible for cell fate commitment in
      normal gut physiology. Where relevant we also mention aberrant deregulation of
      these molecular pathways that results in colon cancer.

PMID- 18808328
TI  - Subsystem organization of the mammalian sense of smell.
AB  - The mammalian olfactory system senses an almost unlimited number of chemical
      stimuli and initiates a process of neural recognition that influences nearly
      every aspect of life. This review examines the organizational principles
      underlying the recognition of olfactory stimuli. The olfactory system is composed
      of a number of distinct subsystems that can be distinguished by the location of
      their sensory neurons in the nasal cavity, the receptors they use to detect
      chemosensory stimuli, the signaling mechanisms they employ to transduce those
      stimuli, and their axonal projections to specific regions of the olfactory
      forebrain. An integrative approach that includes gene targeting methods, optical
      and electrophysiological recording, and behavioral analysis has helped to
      elucidate the functional significance of this subsystem organization for the
      sense of smell.

PMID- 18808329
TI  - Special issue on the RECOMB Satellite Workshop on Comparative Genomics 2007.
      Preface.

PMID- 18808330
TI  - Reconciliation with non-binary species trees.
AB  - Reconciliation extracts information from the topological incongruence between
      gene and species trees to infer duplications and losses in the history of a gene
      family. The inferred duplication-loss histories provide valuable information for
      a broad range of biological applications, including ortholog identification,
      estimating gene duplication times, and rooting and correcting gene trees. While
      reconciliation for binary trees is a tractable and well studied problem, there
      are no algorithms for reconciliation with non-binary species trees. Yet a
      striking proportion of species trees are non-binary. For example, 64% of branch
      points in the NCBI taxonomy have three or more children. When applied to non
      binary species trees, current algorithms overestimate the number of duplications
      because they cannot distinguish between duplication and incomplete lineage
      sorting. We present the first algorithms for reconciling binary gene trees with
      non-binary species trees under a duplication-loss parsimony model. Our algorithms
      utilize an efficient mapping from gene to species trees to infer the minimum
      number of duplications in O(|V(G) | x (k(S) + h(S))) time, where |V(G)| is the
      number of nodes in the gene tree, h(S) is the height of the species tree and k(S)
      is the size of its largest polytomy. We present a dynamic programming algorithm
      which also minimizes the total number of losses. Although this algorithm is
      exponential in the size of the largest polytomy, it performs well in practice for
      polytomies with outdegree of 12 or less. We also present a heuristic which
      estimates the minimal number of losses in polynomial time. In empirical tests,
      this algorithm finds an optimal loss history 99% of the time. Our algorithms have
      been implemented in NOTUNG, a robust, production quality, tree-fitting program,
      which provides a graphical user interface for exploratory analysis and also
      supports automated, high-throughput analysis of large data sets.

PMID- 18808332
TI  - Heart disease prevention practices among immigrant Vietnamese women.
AB  - BACKGROUND: Cardiovascular disease is a leading cause of death in the United
      States as well as in many countries around the world, including Vietnam. METHODS:
      Using data from a household survey of Vietnamese American women aged 20-79 years
      in Seattle, Washington, collected in 2006 and 2007, we examined heart disease
      prevention practices. Multivariable analyses were conducted to examine the
      relationship between demographic factors and preventive behaviors. RESULTS: A
      total of 1523 immigrant women completed interviews. The average daily consumption
      of fruits and vegetables was 3.5 servings, and 31% of our sample reported being
      physically active (engaging in at least 30 minutes of physical activity 5 or more
      days per week). Few respondents reported being current smokers (1.5%). Over three
      quarters of women had received a recent blood pressure check and a recent
      cholesterol check. Age and length of time in the United States were strongly
      associated with several cardiovascular prevention behaviors. CONCLUSIONS: Our
      findings confirm the need for continued efforts to develop and implement targeted
      educational campaigns to reduce the risk of cardiovascular disease among
      Vietnamese American women.

PMID- 18808333
TI  - A new recombinant bacille Calmette-Guerin vaccine safely induces significantly
      enhanced tuberculosis-specific immunity in human volunteers.
AB  - BACKGROUND: One strategy for improving anti-tuberculosis (TB) vaccination
      involves the use of recombinant bacille Calmette-Guerin (rBCG) overexpressing
      protective TB antigens. rBCG30, which overexpresses the Mycobacterium
      tuberculosis secreted antigen Ag85b, was the first rBCG shown to induce
      significantly greater protection against TB in animals than parental BCG.
      METHODS: We report here the first double-blind phase 1 trial of rBCG30 in 35
      adults randomized to receive either rBCG30 or parental Tice BCG intradermally.
      Clinical reactogenicity was assessed, and state-of-the-art immunological assays
      were used to study Ag85b-specific immune responses induced by both vaccines.
      RESULTS: Similar clinical reactogenicity occurred with both vaccines. rBCG30
      induced significantly increased Ag85b-specific T cell lymphoproliferation,
      interferon (IFN)-gamma secretion, IFN-gamma enzyme-linked immunospot responses,
      and direct ex vivo intracellular IFN-gamma responses. Additional flow cytometry
      studies measuring carboxyfluorescein succinimidyl ester dilution and
      intracellular cytokine production demonstrated that rBCG30 significantly enhanced
      the population of Ag85b-specific CD4(+) and CD8(+) T cells capable of concurrent
      expansion and effector function. More importantly, rBCG30 significantly increased
      the number of Ag85b-specific T cells capable of inhibiting intracellular
      mycobacteria. CONCLUSIONS: These results provide proof of principal that rBCG can
      safely enhance human TB immunity and support further development of rBCG
      overexpressing Ag85b for TB vaccination.

PMID- 18808334
TI  - Community outbreak of Mycoplasma pneumoniae infection: school-based cluster of
      neurologic disease associated with household transmission of respiratory illness.
AB  - BACKGROUND: We investigated an outbreak of severe neurologic disease and
      pneumonia that occurred among students at 4 schools in Rhode Island. METHODS: We
      identified cases of encephalitis, encephalomyelitis, and pneumonia that occurred
      among schoolchildren from 1 September 2006 through 9 February 2007, and we
      performed serologic tests, polymerase chain reaction (PCR) analysis, and culture
      for the detection of multiple pathogens in oropharyngeal and nasopharyngeal
      specimens. Students with positive results of M. pneumoniae IgM serologic testing
      and no alternative diagnosis were considered to be infected with M. pneumoniae.
      At school A, we used questionnaires to identify students and their household
      contacts who made visits to physicians for pneumonia and cough. We compared
      observed and expected rates of pneumonia. RESULTS: Rates of pneumonia among
      elementary students (122 cases/1000 student-years) were > 5-fold higher than
      expected. Three students had encephalitis or encephalomyelitis, and 76 had
      pneumonia. Of these 2 groups of students, 2 (66%) and 57 students (75%),
      respectively, had M. pneumoniae infection. M. pneumoniae was detected by PCR in
      10 students with pneumonia; 5 of these specimens were cultured, and M. pneumoniae
      was isolated in 4. Of 202 households of students attending school A, 20 (10%)
      accounted for 61% of visits to physicians for pneumonia or cough. Of 19 household
      contacts of students with pneumonia, 8 (42%) developed pneumonia and 6 (32%)
      reported visits for cough. CONCLUSIONS: M. pneumoniae caused a community-wide
      outbreak of cough illness and pneumonia and was associated with the development
      of life-threatening neurologic disease. Although M. pneumoniae was detected in
      schools, its transmission in households amplified the outbreak. Interrupting
      household transmission should be a priority during future outbreaks.

PMID- 18808335
TI  - Broad immunogenicity of a multigene, multiclade HIV-1 DNA vaccine boosted with
      heterologous HIV-1 recombinant modified vaccinia virus Ankara.
AB  - BACKGROUND: A human immunodeficiency virus (HIV) vaccine that limits disease and
      transmission is urgently needed. This clinical trial evaluated the safety and
      immunogenicity of an HIV vaccine that combines a plasmid-DNA priming vaccine and
      a modified vaccinia virus Ankara (MVA) boosting vaccine. METHODS: Forty healthy
      volunteers were injected with DNA plasmids containing gp160 of HIV-1 subtypes A,
      B, and C; rev B; p17/p24 gag A and B, and RTmut B by use of a needle-free
      injection system. The vaccine was administered intradermally or intramuscularly,
      with or without recombinant granulocyte macrophage colony-stimulating factor, and
      boosted with a heterologous MVA containing env, gag, and pol of CRF01A_E. Immune
      responses were monitored with HIV-specific interferon (IFN)-gamma and interleukin
      (IL)-2 ELISpot and lymphoproliferative assays (LPAs). RESULTS: Vaccine-related
      adverse events were mild and tolerable. After receipt of the DNA priming vaccine,
      11 (30%) of 37 vaccinees had HIV-specific IFN-gamma responses. After receipt of
      the MVA boosting vaccine, ELISpot assays showed that 34 (92%) of 37 vaccinees had
      HIV-specific IFN-gamma responses, 32 (86%) to Gag and 24 (65%) to Env. IFN-gamma
      production was detected in both the CD8(+) T cell compartment (5 of 9 selected
      vaccinees) and the CD4(+) T cell compartment (9 of 9). ELISpot results showed
      that 25 (68%) of 37 vaccinees had a positive IL-2 response and 35 (92%) of 38 had
      a positive LPA response. Of 38 subjects, a total of 37 (97%) were responders. One
      milligram of HIV-1 DNA administered intradermally was as effective as 4 mg
      administered intramuscularly in priming for the MVA boosting vaccine. CONCLUSION:
      This HIV-DNA priming-MVA boosting approach is safe and highly immunogenic. TRIALS
      REGISTRATION: International Standard Randomised Controlled Trial number:
      ISRCTN32604572 .

PMID- 18808336
TI  - Complexity of Plasmodium falciparum clinical samples from Uganda during short
      term culture.
AB  - We cultured Plasmodium falciparum parasites from 98 Ugandan children with malaria
      and determined the complexity of infection (COI) on the basis of msp-2
      polymorphisms daily for 9 days. The mean COI decreased during culture from 1.73
      to 1.56. New strains appeared after day 0 in 20 cultures. Strains disappeared
      after day 0 in 56% of 45 cultures that were initially mixed; persisting strains
      more commonly had wild-type dhfr (C59) and dhps (K540) sequences and mutant
      pfmdr1 (86Y) sequences. Thus, initial genotypes offer an imperfect representation
      of clinical COI. Loss of strains in culture may be due to diminished fitness of
      some drug-resistant strains.

PMID- 18808337
TI  - Cross-protection between successive waves of the 1918-1919 influenza pandemic:
      epidemiological evidence from US Army camps and from Britain.
AB  - BACKGROUND: The current worst-case scenario for pandemic influenza planning is
      based on the catastrophic 1918-1919 pandemic. In this article, we examine the
      strength of cross-protection between successive waves of the 1918-1919 pandemic,
      which has remained a long-standing issue of debate. METHOD: We studied monthly
      hospitalization and mortality rates for respiratory illness in 37 army camps, as
      well as the rates of repeated episodes of influenza infection during January
      December 1918 in 8 military and civilian settings in the United States and
      Britain. RESULTS: A first wave of respiratory illness occurred in US Army camps
      during March-May 1918 and in Britain during May-June, followed by a lethal second
      wave in the fall. The first wave was characterized by high morbidity but had a
      lower fatality rate than the second wave (1.1% vs. 4.7% among hospitalized
      soldiers; P < .001). Based on repeated illness data, the first wave provided 35%
      94% protection against clinical illness during the second wave and 56%-89%
      protection against death (P < .001). CONCLUSION: Exposure to influenza in the
      spring and summer of 1918 provided mortality and morbidity protection during the
      fall pandemic wave. The intensity of the first wave may have differed across US
      cities and countries and may partly explain geographical variation in pandemic
      mortality rates in the fall. Pandemic preparedness plans should consider that
      immune protection could be naturally acquired during a first wave of mild
      influenza illnesses.

PMID- 18808338
TI  - Safety and immunogenicity of an inactivated influenza A/H5N1 vaccine given with
      or without aluminum hydroxide to healthy adults: results of a phase I-II
      randomized clinical trial.
AB  - BACKGROUND: Dose-sparing strategies are being explored for vaccines against
      pandemic influenza. We evaluated the dose-sparing potential of aluminum hydroxide
      (AlOH) adjuvant. METHODS: A total of 600 healthy subjects (age, 18-49 years) were
      randomized to receive 2 vaccinations 1 month apart with subvirion inactivated
      influenza A/H5N1 vaccine containing 7.5, 15, or 45 microg of hemagglutinin (HA),
      with or without 600 microg of aluminum hydroxide (AlOH), or 3.75 microg of HA,
      with or without 300 microg of AlOH. Serum specimens were obtained for antibody
      assays before and 1 month after each vaccination. RESULTS: All formulations were
      safe. Injection site discomfort was more frequent in groups given vaccines with
      AlOH. Dose-related increases in antibody responses were noted after both
      vaccinations (P< .001) geometric mean titers of hemagglutination inhibition
      antibody in vaccines with and without AlOH, respectively, were 5.4 and 5.4 for
      subjects who received 3.75 microg of HA, 7.7 and 5.3 for those who received 7.5
      microg of HA, 8.1 and 8.5 for those who received 15 microg of HA, and 14.8 and 12
      for those who received 45 microg of HA. A > or =4-fold increase in titer was
      observed in 2% and 2% of subjects who received 3.75 microg of HA with or without
      AlOH, respectively; in 14% and 0% who received 7 microg of HA; in 14% and 13% who
      received 15 microg of HA; and in 33% and 25% who received 45 microg of HA.
      Addition of AlOH enhanced responses only for subjects who received 7.5 microg of
      HA, but responses in subjects who received 7.5 microg of HA without AlOH were
      unexpectedly low. CONCLUSION: Overall, a meaningful beneficial effect of AlOH
      adjuvant was not observed. TRIAL REGISTRATION: ClinicalTrials.gov identifier:
      NCT00296634 .

PMID- 18808339
TI  - Amplification of pvmdr1 associated with multidrug-resistant Plasmodium vivax.
AB  - BACKGROUND: Multidrug-resistant strains of Plasmodium vivax are emerging in
      Southeast Asia. METHODS: In vitro drug susceptibility and pvmdr1 genotype were
      determined in P. vivax field isolates from Indonesia and Thailand. RESULTS:
      Increased pvmdr1 copy number was present in 21% of isolates from Thailand (15/71)
      and none from Indonesia (0/114; P < .001). Compared with Indonesian isolates, the
      median IC(50) of Thai isolates was lower for chloroquine (36 vs. 114 nmol/L; P <
      .001) but higher for amodiaquine (34 vs. 13.7 nmol/L; P = .032), artesunate (8.33
      vs. 1.58 nmol/L; P < .001), and mefloquine (111 vs. 9.87 nmol/L; P < .001). In 11
      cryopreserved Thai isolates, those with increased pvmdr1 copy number had a higher
      IC(50) for mefloquine (78.6 vs. 38 nmol/L for single-copy isolates; P = .006).
      Compared with isolates with the wild-type allele, the Y976F mutation of pvmdr1
      was associated with reduced susceptibility to chloroquine (154 nmol/L [range, 4.6
      3505] vs. 34 nmol/L [range, 6.7-149]; P < .001) but greater susceptibility to
      artesunate (1.8 vs. 9.5 nmol/L; P = .009) and mefloquine (14 vs. 121 nmol/L; P <
      .001). CONCLUSIONS: Amplification of pvmdr1 and single-nucleotide polymorphisms
      are correlated with susceptibility of P. vivax to multiple antimalarial drugs.
      Chloroquine and mefloquine appear to exert competitive evolutionary pressure on
      pvmdr1, similar to that observed with pfmdr1 in Plasmodium falciparum.

PMID- 18808340
TI  - Recommendations for metrics for multidrug-resistant organisms in healthcare
      settings: SHEA/HICPAC Position paper .

PMID- 18808341
TI  - Matched case-control analysis of polymicrobial bloodstream infection in a
      neonatal intensive care unit.
AB  - OBJECTIVE: To compare and contrast the epidemiology of polymicrobial and
      monomicrobial bloodstream infections (BSIs) in newborn intensive care unit (NICU)
      patients. DESIGN: Retrospective, matched case-control study. SETTING: The Yale
      New Haven Hospital NICU from 1989 through 2006. SUBJECTS: NICU patients with
      BSIs. METHODS: Each neonate with polymicrobial BSI (case patient) was matched to
      one neonate with monomicrobial BSI (control patient), by birth date, weight, and
      sex; and univariate and multivariate analyses were performed. RESULTS: One
      hundred five cases of polymicrobial BSI were identified in 102 infants,
      representing 10% of all neonatal BSIs in our institution. Coagulase-negative
      staphylococci were the most common organisms recovered from culture. Infants with
      polymicrobial BSI had later onset of infection than infants with monomicrobial
      BSI (mean day of life, 37.5 vs 24.0; P<.001). Polymicrobial BSI occurred more
      frequently among infants with a severe underlying condition than in those without
      such a condition (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.1-3.2)
      and among infants requiring an indwelling central venous catheter for a prolonged
      duration (mean, 16.9 days, compared with 9.8 days for infants with monomicrobial
      BSI; P=.001). Multivariate analysis revealed that later onset of infection
      (adjusted OR [aOR], 1.02; 95% CI, 1.00-1.04) and presence of a severe underlying
      condition (aOR, 1.91; 95% CI, 1.12-3.38) were independent risk factors for
      polymicrobial BSI. No differences in outcome or mortality were observed.
      CONCLUSIONS: Changes in the microbiology and epidemiology of NICU-related
      polymicrobial BSI have occurred since the last North American review. In the
      present study, although differences were observed, most risk factors and outcomes
      were similar between monomicrobial BSI and polymicrobial BSI. Epidemiologic
      surveillance is critical to identify trends associated with neonatal
      polymicrobial BSI, particularly those that may impact preventative strategies,
      diagnostic measures, and therapeutic interventions.

PMID- 18808342
TI  - Complex surgical site infections and the devilish details of risk adjustment:
      important implications for public reporting.
AB  - OBJECTIVE: To validate the National Nosocomial Infection Surveillance (NNIS) risk
      index as a tool to account for differences in case mix when reporting rates of
      complex surgical site infection (SSI). DESIGN: Prospective cohort study. SETTING:
      Twenty-four community hospitals in the southeastern United States. METHODS: We
      identified surgical procedures performed between January 1, 2005, and June 30,
      2007. The Goodman-Kruskal gamma or G statistic was used to determine the
      correlation between the NNIS risk index score and the rates of complex SSI (not
      including superficial incisional SSI). Procedure-specific analyses were performed
      for SSI after abdominal hysterectomy, cardiothoracic procedures, colon
      procedures, insertion of a hip prosthesis, insertion of a knee prosthesis, and
      vascular procedures. RESULTS: A total of 2,257 SSIs were identified during the
      study period (overall rate, 1.19 SSIs per 100 procedures), of which 1,093 (48.4%)
      were complex (0.58 complex SSIs per 100 procedures). There were 45 complex SSIs
      identified following 7,032 abdominal hysterectomies (rate, 0.64 SSIs per 100
      procedures); 63 following 5,318 cardiothoracic procedures (1.18 SSIs per 100
      procedures); 139 following 5,144 colon procedures (2.70 SSIs per 100 procedures);
      63 following 6,639 hip prosthesis insertions (0.94 SSIs per 100 procedures); 73
      following 9,658 knee prosthesis insertions (0.76 SSIs per 100 procedures); and 55
      following 6,575 vascular procedures (0.84 SSIs per 100 procedures). All 6
      procedure-specific rates of complex SSI were significantly correlated with
      increasing NNIS risk index score (P<.05). CONCLUSIONS: Some experts recommend
      reporting rates of complex SSI to overcome the widely acknowledged detection bias
      associated with superficial incisional infection. Furthermore, it is necessary to
      compensate for case-mix differences in patient populations, to ensure that
      intrahospital comparisons are meaningful. Our results indicate that the NNIS risk
      index is a reasonable method for the risk stratification of complex SSIs for
      several commonly performed procedures.

PMID- 18808343
TI  - Coadministration of oral levofloxacin with agents that impair absorption: impact
      on antibiotic resistance.
AB  - Coadministration of oral divalent or trivalent cation-containing compounds with
      oral fluoroquinolones may impair fluoroquinolone absorption. Among 3,134 patients
      who received a course of oral levofloxacin, coadministration was significantly
      associated with subsequent identification of a levofloxacin-resistant isolate.
      Strategies to curb the emergence of fluoroquinolone resistance should include
      avoiding the coadministration of divalent or trivalent cation-containing
      compounds and fluoroquinolone.

PMID- 18808344
TI  - Surveillance of central venous catheter-associated bloodstream infection in a
      Scottish hematology unit.

PMID- 18808346
TI  - Has the time come to recommend the use of alcohol-based hand rub to hospitalized
      patients?

PMID- 18808347
TI  - Trends in Stenotrophomonas maltophilia bloodstream infection in relation to usage
      density of cephalosporins and carbapenems during 7 years.

PMID- 18808348
TI  - Clinical features and treatment outcomes of infections caused by Sphingomonas
      paucimobilis.

PMID- 18808349
TI  - Surveillance for mupirocin resistance among methicillin-resistant Staphylococcus
      aureus clinical isolates.

PMID- 18808350
TI  - Finding the path of least antimicrobial resistance in pyelonephritis.

PMID- 18808351
TI  - Biased genotype distributions of Candida albicans strains associated with
      vulvovaginal candidosis and candidal balanoposthitis in China.
AB  - BACKGROUND: Vulvovaginal candidosis (VVC), which is most frequently caused by
      Candida albicans, is one of the most common vaginal infections and is a common
      problem worldwide. Despite the fact that extensive epidemiological studies have
      been performed, what triggers VVC, especially recurrence of the infection, is
      still uncertain. METHODS: Genotypes of C. albicans strains associated with VVC
      and balanoposthitis and of strains isolated from samples from vaginas of
      asymptomatic women and from various extragenital sites were determined with use
      of C. albicans microsatellite locus I polymorphism analysis. Genetic similarity
      of representative strains with the same and different C. albicans microsatellite
      locus I genotypes were examined by sequence analysis of housekeeping genes
      CaADP1, CaSYA1, and CaVPS13. RESULTS: The C. albicans microsatellite locus I
      genotypes of independent C. albicans strains isolated from samples from
      extragenital sites were mostly of individual specificity. In contrast, strains
      associated with VVC were mainly concentrated to a few genotypes, with genotypes
      30-45 and 32-46 being the most common. The overall frequencies of the 2 genotypes
      among C. albicans strains from vaginal samples from patients with VVC and from
      asymptomatic women were 59.1% and 24.0%, respectively (P = .002); the frequencies
      among patients with complicated VVC and among patients with uncomplicated VVC
      were 69.2% and 35.7%, respectively (P = .003). A similar genotype distribution
      pattern of C. albicans strains associated with balanoposthitis was also revealed.
      The genetic similarity of strains with the dominant genotypes associated with
      both VVC and balanoposthitis was confirmed by sequence analysis of the 3 genes.
      CONCLUSIONS: The results suggest the existence of vaginopathic C. albicans
      strains with enhanced virulence and tropism for the vagina and the high
      possibility of sexual transmission of genital C. albicans infection.
      Identification of specific genotypes that correlate with severity of VVC is also
      of diagnostic and therapeutic significance.

PMID- 18808352
TI  - Factors associated with overall and attributable mortality in invasive
      aspergillosis.
AB  - BACKGROUND: Invasive aspergillosis is associated with high death rates. Factors
      associated with increased mortality have not yet been identified in a large
      population of patients with various underlying conditions. METHODS: We
      retrospectively reviewed 385 cases of suspected or documented aspergillosis that
      occurred during a 9-year period. We identified 289 episodes that fulfilled the
      criteria for possible, probable, or proven invasive aspergillosis according to
      the international definition criteria and that was treated with an anti
      Aspergillus active antifungal drug. Clinical and microbiological variables were
      analyzed for their effects on overall and attributable mortality. Significant
      variables in univariate analysis were introduced into a multivariate Cox model.
      RESULTS: Twelve-week overall and disease-specific survival rates were 52.2% (95%
      confidence interval, 46.5%-57.9%) and 59.8% (95% confidence interval, 54.0%
      65.4%), respectively. Receipt of allogeneic hematopoietic stem cell or solid
      organ transplant, progression of underlying malignancy, prior respiratory
      disease, receipt of corticosteroid therapy, renal impairment, low monocyte
      counts, disseminated aspergillosis, diffuse pulmonary lesions, pleural effusion,
      and proven or probable (as opposed to possible) aspergillosis are predictors of
      increased overall mortality. Similar factors are also predictors of increased
      attributable mortality, with the following exceptions: pleural effusion and low
      monocyte counts have no impact, whereas neutropenia is associated with a higher
      attributable mortality. CONCLUSIONS: Identification of predictors of death helps
      in the identification of patients who could benefit from more-aggressive
      therapeutic strategies. Initiation of therapy at the stage of possible infection
      improves outcome, and this finding calls for the development of efficient
      preemptive strategies to fill the gap between empirical and directed therapy.

PMID- 18808353
TI  - Rickettsia parkeri rickettsiosis and its clinical distinction from Rocky Mountain
      spotted fever.
AB  - BACKGROUND: Rickettsia parkeri rickettsiosis, a recently identified spotted fever
      transmitted by the Gulf Coast tick (Amblyomma maculatum), was first described in
      2004. We summarize the clinical and epidemiological features of 12 patients in
      the United States with confirmed or probable disease attributable to R. parkeri
      and comment on distinctions between R. parkeri rickettsiosis and other United
      States rickettsioses. METHODS: Clinical specimens from patients in the United
      States who reside within the range of A. maculatum for whom an eschar or
      vesicular rash was described were evaluated by > or =1 laboratory assays at the
      Centers for Disease Control and Prevention (Atlanta, GA) to identify probable or
      confirmed infection with R. parkeri. RESULTS: During 1998-2007, clinical samples
      from 12 patients with illnesses epidemiologically and clinically compatible with
      R. parkeri rickettsiosis were submitted for diagnostic evaluation. Using indirect
      immunofluorescence antibody assays, immunohistochemistry, polymerase chain
      reaction assays, and cell culture isolation, we identified 6 confirmed and 6
      probable cases of infection with R. parkeri. The aggregate clinical
      characteristics of these patients revealed a disease similar to but less severe
      than classically described Rocky Mountain spotted fever. CONCLUSIONS: Closer
      attention to the distinct clinical features of the various spotted fever
      syndromes that exist in the United States and other countries of the Western
      hemisphere, coupled with more frequent use of specific confirmatory assays, may
      unveil several unique diseases that have been identified collectively as Rocky
      Mountain spotted fever during the past century. Accurate assessments of these
      distinct infections will ultimately provide a more valid description of the
      currently recognized distribution, incidence, and case-fatality rate of Rocky
      Mountain spotted fever.

PMID- 18808354
TI  - Healthcare epidemiology: gastrointestinal flu: norovirus in health care and long
      term care facilities.
AB  - Noroviruses, recognized as the leading global cause of viral gastroenteritis and
      a major contributor to food-borne illness, present a growing challenge in health
      care and long-term care facilities. The virus spreads easily and by multiple
      routes. A visitor to a ward might initiate an outbreak by person-to-person
      contact, vomiting staff members or patients can disseminate the virus by airborne
      means, and contaminated surfaces, such as doorknobs and computer keyboards, can
      sustain an epidemic. In addition, although self-limited in healthy hosts, the
      virus can cause increased morbidity in more-vulnerable people. The GII.4 strain
      of the virus now dominates in multiple recent worldwide epidemics as well as in
      health care and long-term care facilities. Much like the influenza virus,
      norovirus appears to evolve by antigenic drift and evading the immune system,
      causing waves of global epidemics. Previous attempts at controlling outbreaks,
      both in the community and in closed facilities, provide guidance about the
      vigilance and action required by the health care community to diminish the
      clinical impact of norovirus infection.

PMID- 18808355
TI  - Role of Klebsiella oxytoca in antibiotic-associated diarrhea.
AB  - BACKGROUND: Klebsiella oxytoca was recently shown to be the causative agent of
      antibiotic-associated hemorrhagic colitis. Because it is unclear whether K.
      oxytoca also causes nonhemorrhagic antibiotic-associated diarrhea, our study
      investigated a possible association between K. oxytoca and that disorder.
      METHODS: A total of 371 consecutive patients were recruited into 4 study groups:
      (1) group A+D+ (patients who received antibiotics and experienced diarrhea; n =
      107), (2) group A+D- (patients who received antibiotics but did not experience
      diarrhea; np93), (3) group A-D+ (patients who experienced acute-onset diarrhea
      but did not receive antibiotics; n = 60), and (4) group A-D- (patients without
      diarrhea who did not receive antibiotics; n = 111). Stool samples were plated on
      MacConkey agar and K. oxytoca was identified using a standard test kit.
      Clostridium difficile was detected by a toxin A/B antigen test. K. oxytoca
      strains were tested for cytotoxicity with use of cell-culture assays. RESULTS: In
      15 of 371 stool samples, K. oxytoca strains were isolated during the study
      period. There was no significant difference in the distribution of K. oxytoca
      among the 4 study groups. Six of the 15 strains were found to be toxin producing.
      Three of the toxin-producing strains caused antibiotic-associated hemorrhagic
      colitis. No case of nonhemorrhagic antibiotic-associated diarrhea due to toxin
      producing K. oxytoca was detected. CONCLUSION: K. oxytoca is not the causative
      agent of nonhemorrhagic antibiotic-associated diarrhea. This is in contrast to
      the distinct clinical entity of antibiotic-associated hemorrhagic colitis.
      Testing for K. oxytoca is therefore only warranted for patients who experience
      bloody diarrhea during antibiotic therapy.

PMID- 18808356
TI  - The use of rifampicin-miconazole-impregnated catheters reduces the incidence of
      femoral and jugular catheter-related bacteremia.
AB  - BACKGROUND: The guidelines of the Centers for Disease Control and Prevention do
      not recommend the use of an antimicrobial- or antiseptic-impregnated catheter for
      short-term use. In previous studies, we have found a higher incidence of central
      venous catheter-related bacteremia among patients with femoral and central
      jugular accesses than among patients with other venous accesses. OBJECTIVE: The
      objective of our study was to determine the incidence of central venous catheter
      related bacteremia associated with rifampicin-miconazole-impregnated catheters
      and standard catheters in patients with femoral and central jugular venous
      accesses. METHODS: This was a cohort study, conducted in the 24-bed polyvalent
      medical-surgical intensive care unit of a university hospital. We included
      patients who were admitted to the intensive care unit from 1 June 2006 through 30
      September 2007 and who underwent femoral or central jugular venous
      catheterization. RESULTS: We inserted 184 femoral (73 rifampicin-miconazole
      impregnated catheters and 111 standard catheters) and 241 central jugular venous
      catheters (114 rifampicin-miconazole-impregnated catheters and 127 standard
      catheters). We found a lower rate of central venous catheter-related bacteremia
      associated with rifampicin-miconazole-impregnated catheters than with standard
      catheters among patients with femoral access (0 vs. 8.62 cases per 1000 catheter
      days; odds ratio, 0.13; 95% confidence interval, 0.00-0.86; P = .03) and among
      patients with central internal jugular access (0 vs. 4.93 cases per 1000 catheter
      days; odds ratio, 0.13; 95% confidence interval, 0.00-0.93; P = .04).
      CONCLUSIONS: Rifampicin-minonazole-impregnated catheters are associated with a
      statistically significant reduction in the incidence of catheter-related
      bacteremia in patients with short-term catheter use at the central jugular and
      femoral sites.

PMID- 18808357
TI  - HIV/AIDS: epidemiology, pathophysiology, and treatment of Kaposi sarcoma
      associated herpesvirus disease: Kaposi sarcoma, primary effusion lymphoma, and
      multicentric Castleman disease.
AB  - Kaposi sarcoma-associated herpesvirus infection is associated with the
      development of 3 proliferative diseases: Kaposi sarcoma, primary effusion
      lymphoma, and multicentric Castleman disease. These conditions are also
      intimately associated with human immunodeficiency virus infection, and important
      synergistic interactions between these 2 viruses have been described. Despite
      differences in viral gene expression patterns in each condition, Kaposi sarcoma
      associated herpesvirus encodes similar oncogenic proteins that promote the
      activation of sequential and parallel signaling pathways. Therapeutic strategies
      have been implemented to target these unique signaling pathways, and this sort of
      molecular targeting is the focus of many current research efforts. The scope of
      this review is to present contemporary knowledge about the epidemiology,
      virology, and immunology of Kaposi sarcoma-associated herpesvirus and to
      highlight several key oncogene products that may be targets for chemotherapy.

PMID- 18808358
TI  - Emergence of Clostridium difficile infection due to a new hypervirulent strain,
      polymerase chain reaction ribotype 078.
AB  - BACKGROUND: Since 2005, an increase in the prevalence of Clostridium difficile
      infection (CDI) due to polymerase chain reaction ribotype 078 has been noticed in
      The Netherlands. This strain has also been identified as the predominant strain
      in pigs and calves. METHODS: CDI caused by type 078 was studied in relation to
      CDI caused by the hypervirulent type 027 and by types other than 027 and 078.
      Human and porcine isolates were further investigated and characterized by
      multilocus variable number tandem repeat analysis. RESULTS: From February 2005
      through February 2008, the incidence of type 078 among isolates obtained from
      1687 patients increased from 3% to 13%. Compared with patients infected with type
      027, patients infected with type 078 were younger (67.4 vs. 73.5 years; P < .01)
      and more frequently had community-associated disease (17.5% vs. 6.7%; odds ratio,
      2.98; 95% confidence interval, 2.11-8.02); rates of severe diarrhea (38.9% vs.
      40.0%) and attributable mortality (3.8% vs. 4.0%) were similar in both groups.
      Compared with patients infected with other types, patients infected with type 078
      more frequently received fluoroquinolone therapy (29.4% vs. 19.8%; odds ratio,
      2.17; 95% confidence interval, 1.06-4.44). Type 078 isolates contained genes for
      toxin A, toxin B, binary toxin, and a 39-base pair deletion in toxin regulator
      gene (tcdC), as well as a point mutation at position 184, resulting in a stop
      codon. Multilocus variable number tandem repeat analysis of 54 human and 11
      porcine isolates revealed 4 clonal complexes containing both porcine and human
      isolates. CONCLUSIONS: CDI due to type 078 and CDI due to type 027 present with
      similar severity, but CDI due to type 078 affects a younger population and is
      more frequently community associated. C. difficile type 078 isolates from humans
      and pigs are highly genetically related.

PMID- 18808359
TI  - Genital tract leukocytes and shedding of genital HIV type 1 RNA.
AB  - BACKGROUND: The mechanism of human immunodeficiency virus (HIV) transmission via
      heterosexual intercourse is unknown. We sought to determine whether the presence
      of inflammatory cells in the vagina is associated with the presence of genital
      tract HIV type 1 (HIV-1) RNA. METHODS: Analysis of a longitudinal prospective
      cohort was performed. Women with HIV-1 infection were assessed with use of paired
      plasma and cervicovaginal lavage specimens. Viral load measurements were
      performed using nucleic acid sequence-based amplification. White blood cells
      found in the genital tract (GT WBCs) were quantified using a hemacytometer.
      Common lower genital tract infections assessed for association with viral
      shedding (i.e., genital tract viral load [GTVL]) included bacterial vaginosis,
      candidiasis, and trichomoniasis. Generalized estimating equations were used to
      estimate the prevalence and odds of detectable GTVL by GT WBC. The association
      was examined both in the presence and in the absence of lower genital tract
      infections. RESULTS: A total of 97 women and 642 visits were included in the
      analysis. Median duration of follow-up was 30.4 months. Thirty women (31%) had
      detectable GTVL at any visit. The median CD4 cell count at baseline was 525
      cells/muL. Most women were antiretroviral therapy naive at baseline. After
      adjustment for plasma viral load, the odds of detectable GTVL increased as GT WBC
      increased, with an odds ratio of 1.36 (95% confidence interval, 1.1-1.7) per 1000
      cell increase in GT WBC among women without lower genital tract infections. After
      adjustment for plasma viral load and lower genital tract infections by
      incorporating them in a regression model, GT WBC remained significantly
      associated with GTVL, with an adjusted odds ratio of 1.22 (95% confidence
      interval, 1.08-1.37). CONCLUSIONS: The presence of GT WBC is associated with an
      increased risk of detectable GTVL.

PMID- 18808360
TI  - Rate and amplification of drug resistance among previously-treated patients with
      tuberculosis in Kampala, Uganda.
AB  - BACKGROUND: Drug-resistant Mycobacterium tuberculosis has emerged as a global
      threat. In resource-constrained settings, patients with a history of tuberculosis
      (TB) treatment may have drug-resistant disease and may experience poor outcomes.
      There is a need to measure the extent of and risk factors for drug resistance in
      such patients. METHODS: From July 2003 through November 2006, we enrolled 410
      previously treated patients with TB in Kampala, Uganda. We measured the
      prevalence of resistance to first- and second-line drugs and analyzed risk
      factors associated with baseline and acquired drug resistance. RESULTS: The
      prevalence of multidrug-resistant TB was 12.7% (95% confidence interval [95% CI],
      9.6%-16.3%). Resistance to second-line drugs was low. Factors associated with
      multidrug-resistant TB at enrollment included a history of treatment failure
      (odds ratio, 23.6; 95% CI, 7.7-72.4), multiple previous TB episodes (odds ratio,
      15.6; 95% CI, 5.0-49.1), and cavities present on chest radiograph (odds ratio,
      5.9; 95% CI, 1.2-29.5). Among a cohort of 250 patients, 5.2% (95% CI, 2.8%-8.7%)
      were infected with M. tuberculosis that developed additional drug resistance.
      Amplification of drug resistance was associated with existing drug resistance at
      baseline (P < .01) and delayed sputum culture conversion (P < .01). CONCLUSIONS:
      The burden of drug resistance in previously treated patients with TB in Uganda is
      sizeable, and the risk of generating additional drug resistance is significant.
      There is an urgent need to improve the treatment for such patients in low-income
      countries.

PMID- 18808361
TI  - Prevalence and risk factor analysis of trimethoprim-sulfamethoxazole- and
      fluoroquinolone-resistant Escherichia coli infection among emergency department
      patients with pyelonephritis.
AB  - BACKGROUND: High rates of resistance to trimethoprim-sulfamethoxazole (TMP-SMX)
      among uropathogenic Escherichia coli are recognized, and concerns exist about
      emerging fluoroquinolone resistance. METHODS: Adults presenting to 11 US
      emergency departments with (1) flank pain and/or costovertebral tenderness, (2)
      temperature >38 degrees C, and (3) a presumptive diagnosis of pyelonephritis were
      enrolled; patients for whom 1 uropathogen grew on culture were analyzed.
      Epidemiologic and clinical data were collected at the time of care. The
      prevalence of E. coli in vitro antibiotic resistance and risk factors associated
      with TMP-SMX-resistant E. coli infection were determined. RESULTS: Among 403
      women with uncomplicated pyelonephritis caused by E. coli, the mean site rate of
      E. coli resistance to TMP-SMX was 24% (range, 13%-45%). Mean site rates of E.
      coli resistance to ciprofloxacin and levofloxacin were 1% and 3%, respectively.
      Only TMP-SMX exposure within 2 days before presentation and Hispanic ethnicity
      were associated with E. coli resistance to TMP-SMX (compared with resistance
      rates of approximately 20% among women lacking these risk factors); antibiotic
      exposure within 3-60 days before presentation, health care setting exposure
      within 30 days before presentation, history of urinary tract infections, and age
      >55 years were not associated with E. coli resistance to TMP-SMX. Among 207
      patients with complicated pyelonephritis, mean site rates of E. coli resistance
      to ciprofloxacin and levofloxacin were 5% and 6%, respectively. CONCLUSIONS:
      These results suggest that the prevalence of TMP-SMX-resistant infection among
      patients with uncomplicated pyelonephritis is > or =20% in many areas of the
      United States, and risk stratification cannot identify patients at low risk of
      infection. Rates of fluoroquinolone-resistant E. coli infection appear to be low
      among patients with uncomplicated pyelonephritis but higher among those with
      complicated infections. Fluoroquinolones should remain to be the preferred
      empirical treatment for women with uncomplicated pyelonephritis.

PMID- 18808362
TI  - High mortality in invasive aspergillosis: what we need to know for determination
      of poor prognosis and next countermeasures.

PMID- 18808363
TI  - Natural selection on male wealth in humans.
AB  - Although genomic studies suggest that natural selection in humans is ongoing, the
      strength of selection acting on particular characteristics in human populations
      has rarely been measured. Positive selection on male wealth appears to be a
      recurrent feature of human agrarian and pastoralist societies, and there is some
      evidence of it in industrial populations, too. Here we investigate the strength
      of selection on male wealth, first in contemporary Britain using data from the
      National Child Development Study and then across seven other varied human
      societies. The British data show positive selection on male income driven by
      increased childlessness among low-income men but a negative association between
      personal income and reproductive success for women. Across cultures, selection
      gradients for male wealth are weakest in industrial countries and strongest in
      subsistence societies with extensive polygyny. Even the weakest selection
      gradients observed for male wealth in humans are as strong as or stronger than
      selection gradients reported from field studies of other species. Thus, selection
      on male wealth in contemporary humans appears to be ubiquitous and substantial in
      strength.

PMID- 18808364
TI  - Short-term effects of topical tafluprost on retinal blood flow in cats.
AB  - PURPOSE: The aim of this study was to determine the short-term effects of topical
      tafluprost, a novel prostaglandin F(2) derivative, on feline retinal circulation.
      METHODS: Seventeen (17) adult cats were anesthetized with enflurane and
      mechanically ventilated. One (1) drop of tafluprost (0.0015%; n = 8), latanoprost
      (0.005%; n = 5), or control vehicle (n = 4) was instilled in 1 eye and the fellow
      eye was untreated. We measured the intraocular pressure (IOP), vessel diameter,
      and blood velocity simultaneously for 120 min in the large retinal arterioles and
      calculated the retinal blood flow (RBF) with a laser Doppler velocimetry system.
      RESULTS: Tafluprost 0.0015% significantly increased RBF (maximum change, 42.8 +/-
      4.2% [mean +/- standard error of the mean; P < 0.01) and blood velocity (maximum
      change, 24.1 +/- 3.3%; P < 0.01) for 120 min after instillation; there was no
      significant change in vessel diameter. Latanoprost 0.005% significantly increased
      RBF (maximum change, 31.7 +/- 3.4%; P < 0.05); there was no significant change in
      vessel diameter and blood velocity. There were no significant differences in the
      IOP reduction among the three groups. CONCLUSIONS: We observed, for the first
      time, that topical tafluprost significantly increased RBF in cats, suggesting
      that dual-action tafluprost may be a beneficial antiglaucomatous agent for
      reducing IOP and increasing RBF.

PMID- 18808365
TI  - Promoter CpG methylation of oestrogen receptors in leukaemia.
AB  - Previous studies have suggested an important role of ERs (oestrogen receptors) in
      the pathogenesis of leukaemias. However, there is no information so far about the
      epigenetic characteristics of ERalpha isoforms and ERbeta in leukaemias. In the
      present study, the mRNA expression and promoter CpG methylation of ERalpha
      isoforms (i.e. ERalpha-A, -B and -C) and ERbeta in leukaemia cell lines were
      evaluated using RT-PCR (reverse transcription-PCR) and MSP (methylation-specific
      PCR) respectively. The methylation of ERs was further analysed in acute leukaemia
      patients by MSP and direct DNA sequencing. Although all ERalpha isoforms and
      ERbeta were methylated in all leukaemia cell lines, except for ERalpha-C, which
      was unmethylated in HL-60 and K562 cell lines, only the expression of ERalpha-A
      was deficient in all cell lines and its expression could be reactivated by DNA
      demethylation reagents. With regard to the methylation characteristics in acute
      leukaemia patients, only ERalpha-A was inactivated and specifically methylated
      (95%; 38/40) in almost all patients and unmethylated in all healthy controls,
      whereas ERalpha-B, -C and ERbeta were methylated in both patients and healthy
      controls. This result suggested that the methylated status of ERalpha-A might
      serve as an epigenetic biomarker of leukaemias. The present study is the first
      report that demonstrates selective inactivation of ERalpha isoforms through the
      promoter CpG methylation pathway in leukaemias.

PMID- 18808366
TI  - Mechanism of the elevation in cardiolipin during HeLa cell entry into the S-phase
      of the human cell cycle.
AB  - CL (cardiolipin) is a key phospholipid involved in ATP generation. Since
      progression through the cell cycle requires ATP we examined regulation of CL
      synthesis during S-phase in human cells and investigated whether CL or CL
      synthesis was required to support nucleotide synthesis in S-phase. HeLa cells
      were made quiescent by serum depletion for 24 h. Serum addition resulted in
      substantial stimulation of [methyl-(3)H]thymidine incorporation into cells
      compared with serum-starved cells by 8 h, confirming entry into the S-phase. CL
      mass was unaltered at 8 h, but increased 2-fold by 16 h post-serum addition
      compared with serum-starved cells. The reason for the increase in CL mass upon
      entry into S-phase was an increase in activity and expression of CL de novo
      biosynthetic and remodelling enzymes and this paralleled the increase in
      mitochondrial mass. CL de novo biosynthesis from D-[U-(14)C]glucose was elevated,
      and from [1,3-(3)H]glycerol reduced, upon serum addition to quiescent cells
      compared with controls and this was a result of differences in the selection of
      precursor pools at the level of uptake. Triascin C treatment inhibited CL
      synthesis from [1-(14)C]oleate but did not affect [methyl-(3)H]thymidine
      incorporation into HeLa cells upon serum addition to serum-starved cells. Barth
      Syndrome lymphoblasts, which exhibit reduced CL, showed similar [methyl
      (3)H]thymidine incorporation into cells upon serum addition to serum-starved
      cells compared with cells from normal aged-matched controls. The results indicate
      that CL de novo biosynthesis is up-regulated via elevated activity and expression
      of CL biosynthetic genes and this accounted for the doubling of CL seen during S
      phase; however, normal de novo CL biosynthesis or CL itself is not essential to
      support nucleotide synthesis during entry into S-phase of the human cell cycle.

PMID- 18808367
TI  - Predictive value of the decrease in circulating dendritic cell precursors in
      stable coronary artery disease.
AB  - DCs (dendritic cells) are present in atherosclerotic lesions leading to vascular
      inflammation, and the number of vascular DCs increases during atherosclerosis.
      Previously, we have shown that the levels of circulating DCPs (DC precursors) are
      reduced in acute coronary syndromes through vascular recruitment. In the present
      study, we have investigated whether DCP levels are also reduced in stable CAD
      (coronary artery disease). The levels of circulating mDCPs (myeloid DCPs), pDCPs
      (plasmacytoid DCPs) and tDCP (total DCPs) were investigated using flow cytometry
      in 290 patients with suspected stable CAD. A coronary angiogram was used to
      evaluate a CAD score for each patient as follows: (i) CAD excluded (n=57); (ii)
      early CAD (n=63); (iii) moderate CAD (n=85); and (iv) advanced CAD (n=85).
      Compared with controls, patients with advanced stable CAD had lower HDL (high
      density lipoprotein)-cholesterol (P=0.03) and higher creatinine (P=0.003). In
      advanced CAD, a significant decrease in circulating mDCPs, pDCPs and tDCPs was
      observed (each P<0.001). A significant inverse correlation was observed between
      the CAD score and mDCPs, pDCPs or tDCPs (each P<0.001). Patients who required
      percutaneous coronary intervention or coronary artery bypass grafting had less
      circulating mDCPs, pDCPs and tDCPs than controls (each P<0.001). Multiple
      stepwise logistic regression analysis suggested mDCPs, pDCPs and tDCPs as
      independent predictors of CAD. In conclusion, we have shown that patients with
      stable CAD have significantly lower levels of circulating DCPs than healthy
      individuals. Their decrease appears to be an independent predictor of the
      presence of, and subsequent therapeutic procedure in, stable CAD.

PMID- 18808369
TI  - Time-lapse geophysical investigations over a simulated urban clandestine grave.
AB  - A simulated clandestine shallow grave was created within a heterogeneous, made
      ground, urban environment where a clothed, plastic resin, human skeleton, animal
      products, and physiological saline were placed in anatomically correct positions
      and re-covered to ground level. A series of repeat (time-lapse), near-surface
      geophysical surveys were undertaken: (1) prior to burial (to act as control), (2)
      1 month, and (3) 3 months post-burial. A range of different geophysical
      techniques was employed including: bulk ground resistivity and conductivity,
      fluxgate gradiometry and high-frequency ground penetrating radar (GPR), soil
      magnetic susceptibility, electrical resistivity tomography (ERT), and self
      potential (SP). Bulk ground resistivity and SP proved optimal for initial grave
      location whilst ERT profiles and GPR horizontal "time-slices" showed the best
      spatial resolutions. Research suggests that in complex urban made-ground
      environments, initial resistivity surveys be collected before GPR and ERT follow
      up surveys are collected over the identified geophysical anomalies.

PMID- 18808370
TI  - Histologic evidence of repetitive blunt force abdominal trauma in four pediatric
      fatalities.
AB  - In cases of acute fatal child abuse, certain injuries, including cutaneous blunt
      force trauma, skull fractures, subdural hematomas, intra-abdominal hemorrhage,
      and retinal hemorrhages are common and well described in the pediatric and
      forensic literature. These gross findings at autopsy, when taken into
      consideration with scene investigation and interviews with caregivers, may
      indicate both a clear manner and cause of death. In such cases, the discovery of
      additional pathologic changes attributable to older abusive injuries helps
      support a conclusion of death due to inflicted trauma. We discuss four cases of
      fatal child abuse in which acute blunt force abdominal trauma was the cause of
      death. In each of these cases, careful examination with proper sectioning and
      microscopy of select abdominal tissues revealed that the acute tissue trauma was
      superimposed on a background of older, healing injury. This older trauma was
      characterized by classic histologic elements of tissue repair, including
      fibroblast proliferation, early scar formation, increased vascularity, and
      hemosiderin-laden macrophages. Iron and trichrome stains were used to confirm the
      presence of hemosiderin and fibrosis in all four cases, but the recognition of
      fibroblast proliferation and a reactive vascular pattern was best seen on routine
      hematoxylin and eosin stains. The gross and microscopic autopsy findings, along
      with available investigative information, established the diagnosis of chronic
      physical abuse.

PMID- 18808371
TI  - Extraction, derivatization, and analysis of vegetable oils from fire debris.
AB  - Vegetable oils have the ability to spontaneously heat under certain conditions,
      which may lead to spontaneous ignition. While the oils are not often encountered
      in forensic casework, they may be suspected in some fire cases. As these oils are
      not effectively analyzed using traditional fire debris analysis methods, a
      protocol must be established for extracting vegetable oils from fire debris. In
      this study, a protocol was developed for the extraction, derivatization, and
      analysis of vegetable oils from fire debris. Three derivatization methods were
      compared to establish an optimal derivatization procedure to convert the fatty
      acids found in vegetable oils to the fatty acid methyl esters (FAMEs) used in
      analysis. Three different gas chromatograph columns and programs were examined to
      determine which was best suited for the separation and analysis of FAMEs. The
      procedure was tested and refined using a variety of neat and burned vegetable
      oils, in addition to extractions from oils burned on commonly encountered fire
      debris materials. The findings of this research will serve as a starting point
      for further understanding and research of vegetable oils in fire debris.

PMID- 18808372
TI  - An updated validation of Promega's PowerPlex 16 System: high throughput
      databasing under reduced PCR volume conditions on Applied Biosystem's 96
      capillary 3730xl DNA Analyzer.
AB  - The PowerPlex 16 System from Promega Corporation allows single tube multiplex
      amplification of sixteen short tandem repeat (STR) loci including all 13 core
      combined DNA index system STRs. This report presents an updated validation of the
      PowerPlex 16 System on Applied Biosystem's 96 capillary 3730xl DNA Analyzer. The
      validation protocol developed in our laboratory allows for the analysis of 1536
      loci (96 x 16) in c. 50 min. We have further optimized the assay by decreasing
      the reaction volume to one-quarter that recommended by the manufacturer thereby
      substantially reducing the total cost per sample without compromising
      reproducibility or specificity. This reduction in reaction volume has the
      ancillary benefit of dramatically increasing the sensitivity of the assay
      allowing for accurate analysis of lower quantities of DNA. Due to its
      substantially increased throughput capability, this extended validation of the
      PowerPlex 16 System should be useful in reducing the backlog of unanalyzed DNA
      samples currently facing public DNA forensic laboratories.

PMID- 18808373
TI  - Analysis of forensic SNPs in the canine mtDNA HV1 mutational hotspot region.
AB  - A 60 bp sequence variation hotspot in the canine mitochondrial DNA hypervariable
      region 1 was evaluated for its use in forensic investigations. Nineteen
      haplotypes containing 18 single nucleotide polymorphisms were observed among
      laboratory-generated and GenBank-derived domestic dog sequences representing five
      regional localities in the U.S. Samples from the different localities were highly
      variable with the levels of intra-population variability being similar among the
      populations studied. AMOVA further confirmed that there was no significant
      genetic structuring of the populations. Assays using these haplotypes were
      robust, canid specific and portend a rapid method for correctly excluding
      individual dogs as noncontributors of forensic evidence. Species-specificity of
      the primers was confirmed by means of in-tube polymerase chain reaction of human
      and cat DNA and in-silico assessment of the genomes of several animal species.
      Breed-specific fragments were not detected among the common haplotypes but there
      is evidence that this assay may be capable of differentiating domestic dog, wolf,
      and coyote sequences.

PMID- 18808374
TI  - The effect of feeding enrichment upon reported working ability and behavior of
      kenneled working dogs.
AB  - It is widely recommended that kenneled dogs are provided with environmental
      enrichment such as toys or feeding devices. However, the adoption of enrichment
      for military working dogs is impeded by a widespread belief that it reduces their
      motivation to work. Handlers of 22 working German Shepherd dogs were asked to
      rate their dogs on 11 attributes pertaining to working ability, related
      behavioral traits, and health. Eight of the dogs were then provided with daily
      feeding enrichment for 4 months, while the remainder were given equivalent human
      attention. The same 11 traits were scored again following the enrichment period:
      10 changed little over the period while handlers' reports of their dogs' Ability
      to learn from being rewarded increased significantly. Changes for all attributes
      were virtually identical in enriched and control dogs. We conclude that if
      correctly managed, feeding enrichment can be introduced to kenneled working dogs
      without any reported detrimental effects upon working ability, health, or
      behavior.

PMID- 18808376
TI  - Atypical presentation of postpartum cerebral angiopathy shown as a small
      penetrating arterial territory infarct with severe peri-infarct edema.
AB  - Postpartum cerebral angiopathy mostly occurs in the large or medium-sized
      cerebral arteries. In this case, we aimed to report a case of postpartum cerebral
      angiopathy presented as an asymmetrical penetrating arterial territory infarct
      with severe surrounding vasogenic edema. A 26-year-old woman admitted because of
      sudden headache after an attack of seizure. On initial computerized tomography
      (CT), hypodense lesion in the right basal ganglia was observed. The diffusion
      weighted image on 5th day revealed focal acute ischemic infarction with
      surrounding extensive vasogenic edema in right basal ganglia. The CT angiography
      showed multifocal arterial narrowing of intracranial cerebral arteries that
      completely resolved on the follow-up study. This case suggested that asymmetrical
      small penetrating arterial territory infarct can occur as an atypical
      presentation of postpartum cerebral angiopathy.

PMID- 18808377
TI  - Influence of forward head posture on condylar position.
AB  - There are several reports suggesting that forward head posture is associated with
      temporomandibular disorders and restraint of mandibular growth, possibly due to
      mandibular displacement posteriorly. However, there have been few reports in
      which the condylar position was examined in forward head posture. The purpose of
      this study was to test the hypothesis that the condyle moves posteriorly in the
      forward head posture. The condylar position and electromyography from the
      masseter, temporal and digastric muscles were recorded on 15 healthy male adults
      at mandibular rest position in the natural head posture and deliberate forward
      head posture. The condylar position in the deliberate forward head posture was
      significantly more posterior than that in the natural head posture. The activity
      of the masseter and digastric muscles in the deliberate forward head posture was
      slightly increased. These results suggest that the condyle moves posteriorly in
      subjects with forward head posture.

PMID- 18808378
TI  - Treatment of actinic keratoses with a novel betulin-based oleogel. A prospective,
      randomized, comparative pilot study.
AB  - BACKGROUND: Actinic keratoses (AK) are squamous cell carcinomas in situ and
      require treatment. Betulin-based oleogel prepared from a standardized triterpene
      dry extract from birch bark represents a new topical agent with anti-inflammatory
      and anti-tumor potential. PATIENTS AND METHODS: In the prospective, randomized,
      monocentric phase 2a study 45 patients with < 10 AK were included and randomly
      assigned to one of the three treatment groups. Intervention consisted of topical
      betulin-based oleogel twice daily versus cryotherapy with liquid nitrogen versus
      the combination of cryotherapy with topical betulin-based oleogel. Treatment
      response was assessed clinically after three months. The clinical response was
      graded into complete clearing (100 %), therapy responders (> 75 % clearing of the
      lesions) and non-responders (< 75 % clearing). Additionally, punch biopsies were
      obtained from some patients before and at the end of treatment. RESULTS: Therapy
      with betulin-based oleogel was well tolerated.Three patients discontinued therapy
      because of personal reasons. After three months, the 100% (and > 75%) clearing
      rates of the lesions were as follows: 64% (86%) with betulin-based oleogel (n =
      14),79% (93%) with cryotherapy (n = 14),and 71% (71%) with the combined therapy
      (n = 14). Histological analysis of biopsies taken before and after treatment (n =
      8) showed a reduced degree of dysplasia in the epidermis in all study arms.
      CONCLUSIONS: Betulin-based oleogel seems to be an effective novel approach in the
      topical treatment of actinic keratoses. However,the clinical and histological
      findings of the present pilot study have to be verified against placebo with
      larger case numbers.

PMID- 18808379
TI  - Viral exanthems in childhood. Part 3: Parainfectious exanthems and those
      associated with virus-drug interactions.
AB  - Viruses cause not only direct infectious exanthems, but also parainfectious
      exanthems, which provoke skin alterations via interactions with the immune
      system. These distinct exanthems, for instance Gianotti-Crosti syndrome and
      pityriasis lichenoides group, do not reflect a specific pathogen but can occur in
      the course of many viral infections. In addition, some exanthems result from the
      interaction between viruses and drugs.

PMID- 18808380
TI  - Viral exanthems in childhood--infectious (direct) exanthems. Part 2: Other viral
      exanthems.
AB  - The group of the non-classic infectious exanthems are mostly maculopapular or
      vesicular. The latter changes are typical for infections with varicella-zoster
      virus and Coxsackie viruses. Congenital cytomegalovirus infections are
      characterized by petechiae and purpura, while the papular-purpuric gloves and
      socks syndrome is usually associated with parvovirus B19. Aside from these, the
      non-classic infectious exanthems diseases include nonspecific exanthems coupled
      with respiratory and enteric infections.

PMID- 18808381
TI  - GadX/GadW-dependent regulation of the Escherichia coli acid fitness island:
      transcriptional control at the gadY-gadW divergent promoters and identification
      of four novel 42 bp GadX/GadW-specific binding sites.
AB  - Escherichia coli has the remarkable ability to resist severe acid stress for
      several hours. With the notable exception of the gadBC operon, the most important
      genes involved in acid resistance are present within the acid fitness island
      (AFI), a 15 kb H-NS-repressed and RpoS-controlled genome region. The AraC/XylS
      like transcriptional regulators GadX and GadW are also encoded within this
      region. In this article, we show that gadW transcription occurs from two native
      promoters, which are affected by the transcription of the divergently transcribed
      and GadX-dependent gadY small RNA, and from the gadX promoter. The gadXW
      dicistronic transcript is subjected to post-transcriptional processing in which
      GadY is involved. In contrast, gadW transcription negatively affects gadY
      transcription. By aligning the GadX/GadW binding site on the gadY promoter with
      the GadX/GadW binding sites previously identified in the gadA and gadBC 5'
      regulatory regions, we generated a 42 bp GadX/GadW consensus sequence. DNase I
      footprinting analyses confirmed that a 42 bp GadX/GadW binding site, which
      matched the consensus sequence 5'-WANDNCTDWTWKTRAYATWAWMATG KCTGATNTTTWYNTYAK-3',
      is also present in the regulatory region of the slp-yhiF, hdeAB and gadE-mtdEF
      operons, all of which belong to the AFI. The presence of five GadX/GadW-specific
      binding sites in the AFI suggests that GadX and GadW may act as H-NS counter
      silencers.

PMID- 18808382
TI  - A small-RNA-mediated negative feedback loop controls quorum-sensing dynamics in
      Vibrio harveyi.
AB  - The bioluminescent marine bacterium Vibrio harveyi uses a cell-to-cell
      communication process called quorum sensing (QS) to co-ordinate behaviours in
      response to changes in population density. QS is accomplished through the
      secretion and detection of extracellular signalling molecules called
      autoinducers. At the centre of the V. harveyi QS circuit are five small
      regulatory RNAs called Qrr1-5 which destabilize the mRNA of luxR, encoding LuxR,
      the master transcriptional regulator of QS target genes. Here we show that LuxR
      directly activates transcription of qrr2, qrr3 and qrr4, leading to the rapid
      downregulation of luxR. The LuxR-binding sites in the promoters of qrr2, qrr3 and
      qrr4 were identified and mutated to determine the consequences of this regulatory
      loop on QS dynamics. Disruption of the loop delays the transition from high to
      low cell density, and more significantly, decreases the cell density at which the
      population reaches a quorum. Our results suggest that feedback is essential for
      optimizing the dynamics of the transitions between individual and group
      behaviours.

PMID- 18808383
TI  - Capsular glucan and intracellular glycogen of Mycobacterium tuberculosis:
      biosynthesis and impact on the persistence in mice.
AB  - Mycobacterium tuberculosis and other pathogenic mycobacterial species produce
      large amounts of a glycogen-like alpha-glucan that represents the major
      polysaccharide of their outermost capsular layer. To determine the role of the
      surface-exposed glucan in the physiology and virulence of these bacteria,
      orthologues of the glg genes involved in the biosynthesis of glycogen in
      Escherichia coli were identified in M. tuberculosis H37Rv and inactivated by
      allelic replacement. Biochemical analyses of the mutants and complemented strains
      indicated that the synthesis of glucan and glycogen involves the alpha-1,4
      glucosyltransferases Rv3032 and GlgA (Rv1212c), the ADP-glucose pyrophosphorylase
      GlgC (Rv1213) and the branching enzyme GlgB (Rv1326c). Disruption of glgC reduced
      by half the glucan and glycogen contents of M. tuberculosis, whereas the
      inactivation of glgA and Rv3032 affected the production of capsular glucan and
      glycogen, respectively. Attempts to disrupt Rv3032 in the glgA mutant were
      unsuccessful, suggesting that a functional copy of at least one of the two alpha
      1,4-glucosyltransferases is required for growth. Importantly, the glgA mutant was
      impaired in its ability to persist in mice, suggesting a role for the capsular
      glucan in the persistence phase of infection. Unexpectedly, GlgB was found to be
      an essential enzyme.

PMID- 18808384
TI  - Identification of a novel protein promoting the colonization and survival of
      Finegoldia magna, a bacterial commensal and opportunistic pathogen.
AB  - Anaerobic bacteria dominate the human normal microbiota, but strikingly little is
      known about these commensals. Finegoldia magna is a Gram-positive anaerobe found
      in the skin and at other non-sterile body surfaces, but it is also an
      opportunistic pathogen. This study describes a novel protein designated FAF (F.
      magna adhesion factor) and expressed by more than 90% of F. magna isolates. The
      protein is present in substantial quantities at the F. magna surface but is also
      released from the surface. FAF forms large protein aggregates in solution and
      surface-associated FAF causes bacterial clumping. In skin F. magna bacteria were
      localized to the epidermis, where they adhere to basement membranes. FAF was
      found to mediate this adhesion via interactions with BM-40, a basement membrane
      protein. The biological significance of FAF is further underlined by the
      observation that it blocks the activity of LL-37, a major human antibacterial
      peptide. Altogether, the data demonstrate that FAF plays an important role in
      colonization and survival of F. magna in the human host.

PMID- 18808385
TI  - The genome of Rhodobacter sphaeroides strain 2.4.1 encodes functional cobinamide
      salvaging systems of archaeal and bacterial origins.
AB  - Bacteria and archaea use distinct pathways for salvaging exogenous cobinamide
      (Cbi), a precursor of adenosylcobalamin (coenzyme B(12)). The bacterial pathway
      depends on a bifunctional enzyme with kinase and guanylyltransferase activities
      (CobP in aerobic adenosylcobalamin synthesizers) to convert adenosylcobinamide
      (AdoCbi) to AdoCbi-guanosine diphosphate (AdoCbi-GDP) via an AdoCbi-phosphate
      intermediate. Archaea lack CobP, and use a different strategy for the synthesis
      of AdoCbi-GDP. Archaea cleave off the aminopropanol group of AdoCbi using the
      CbiZ AdoCbi amidohydrolase to generate adenosylcobyric acid, which is converted
      to AdoCbi-phosphate by the CbiB synthetase, and to AdoCbi-GDP by the CobY
      guanylyltransferase. We report phylogenetic, in vivo and in vitro evidence that
      the genome of Rhodobacter sphaeroides encodes functional enzymes for Cbi
      salvaging systems of both bacterial and archaeal origins. Products of the
      reactions were identified by high-performance liquid chromatography, UV-visible
      spectroscopy and bioassay. The cbiZ genes of several bacteria and archaea
      restored Cbi salvaging in a strain of Salmonella enterica unable to salvage Cbi.
      Phylogenetic data led us to conclude that CbiZ is an enzyme of archaeal origin
      that was horizontally transferred to bacteria. Reasons why some bacteria may
      contain both types of Cbi salvaging systems are discussed.

PMID- 18808386
TI  - Heart and iron deficiency anaemia in rats with renal insufficiency: the role of
      hepcidin.
AB  - AIM: Anaemia is prevalent in chronic kidney disease (CKD) and induces significant
      changes in heart and kidney. In this study, we evaluated the relationship between
      iron metabolism, hepcidin and inflammation focusing on left ventricular (LV)
      function, in a remnant kidney rat model. METHODS: Rats with 5/6 subtotal
      nephrectomy (STNx) and sham operation. Haemoglobin (Hb), serum iron (SI),
      fractional shortening (FS%) by echocardiograms were evaluated. Six months after
      STNx, the heart and kidney were processed by immunohistochemistry with antibodies
      against hypoxia-inducible factors (HIF)-1alpha, erythropoietin (EPO), pro
      hepcidin, caspase-3, tumour necrosis factor (TNF)-alpha and interleukin (IL)-6.
      RESULTS: Hb (g/dL) STNx: 10.8 +/- 0.8, sham: 14.7 +/- 0.6 (P < 0.01); SI
      (microg/dL) STNx: 154.5 +/- 24.5, sham: 287.5 +/- 32.1 (P < 0.01); heart weight
      (g) STNx: 2.21 +/- 0.15, sham: 1.12 +/- 0.12 (P < 0.01); FS% STNx: 28.4 +/- 2.5,
      sham: 45.1 +/- 4.1 (P < 0.01). There was a correlation between Hb and FS% (r =
      0.95; P < 0.01) and between SI and FS% (r = 0.86; P < 0.01) in the STNx group.
      Tissue ferritin was reduced in heart and in kidney in the STNx group (P < 0.01).
      HIF-1alpha was expressed in cardiomyocytes (positive cells/area) STNx: 32 +/- 5,
      sham: 4 +/- 1; and tubular cells in STNx group: 70 +/- 16, sham: 10 +/- 3, P <
      0.01. Hepcidin (% staining/area) in heart STNx: 6.6 +/- 0.8, sham: 0.8 +/- 0.1;
      in kidney STNx: 9.7 +/- 2.6, sham: 3.7 +/- 0.9, P < 0.01. EPO (% staining/area)
      in heart STNx: 2.6 +/- 0.4, sham: 0.8 +/- 0.2; in kidney STNx: 10.2 +/- 1.4,
      sham: 1.2 +/- 0.6; P < 0.01. In STNx group positive caspase-3, TNF-alpha and IL-6
      were detected in heart and renal cells. CONCLUSION: Low LV performance is
      associated with iron deficiency anaemia in rats with CKD. Furthermore,
      overproduction of HIF-1alpha and the activation of caspase-3 seem to be
      associated with iron deficiency and with inflammatory markers. Hepcidin seems to
      plays a key role in this mechanism.

PMID- 18808387
TI  - An in vitro investigation of herbs traditionally used for kidney and urinary
      system disorders: potential therapeutic and toxic effects.
AB  - AIM: Renal fibrosis is central to progression of most chronic renal pathologies.
      Antioxidants that protect the tubular epithelium and anti-fibrotics that induce
      apoptosis of pro-fibrotic myofibroblasts without adversely affecting tubular
      epithelium may slow progression of renal fibrosis, while toxic substances may
      exacerbate renal scarring. We investigated 47 herbs for their in vitro toxic or
      antioxidant effects on normal renal mammalian fibroblasts (NRK49F) and tubular
      epithelial cells (NRK52E) to determine their potential value as therapeutic
      agents in renal fibrosis involving oxidative stress. METHODS: Herbs were chosen
      because of their traditional use in kidney or urinary system disorders, or
      because of recent published interest in their therapeutic or toxic potential in
      kidney disease. Extracts of herbs were made using a sequential multi-solvent
      extraction process. Each extract was analysed separately. Extraction solvents
      were ethyl acetate, methanol and 50% aqueous methanol. Cells were treated with
      extracts with/without oxidative stress (1.0 mM hydrogen peroxide). Cellular
      changes (apoptosis, necrosis, mitosis, transdifferentiation) were identified and
      quantified using defined criteria. RESULTS: All extracts of Dioscorea villosa
      showed significant toxicity to both cell lines. At low concentrations (5-50
      microg/mL) they induced epithelial to mesenchymal transdifferentiation, as
      demonstrated by increased immunohistochemistry staining for alpha-smooth muscle
      actin and transforming growth factor-beta1 in treated versus control cells.
      Angelica sinensis, Centella asiatica, Glycyrrhiza glabra, Scutellaria
      lateriflora, and Olea europaea demonstrated strong antioxidant effects in
      epithelial cells and/or apoptotic effects on fibroblasts. CONCLUSION: This
      investigation has revealed renotoxicity of D. villosa and anti-fibrotic, oxidant
      potential of several herbal extracts, all of which require further study.

PMID- 18808388
TI  - Race and end-stage renal disease in the United States Medicare population: the
      disparity persists.
AB  - AIM: A marked preponderance of end-stage renal disease among African Americans
      was described more than two decades ago. The objective of this study was to
      determine whether racial disparities in end-stage renal disease in the United
      States have changed over time. METHODS: The authors compared renal replacement
      therapy rates in five biennial cohorts (1993-1994, 1995-1996, 1997-1998, 1999
      2000, 2001-2002; n = 6 315 283), using annual random samples of 5% of the US
      Medicare population and the United States Renal Data System registry. RESULTS:
      The proportion of African American subjects rose from 8.8% in the first cohort to
      9.4% in the last. Renal replacement therapy rates (per 1000 patient-years) among
      white Americans in successive cohorts were 0.84, 0.96, 1.08, 1.16 and 1.20,
      compared with 2.98, 3.24, 3.65, 3.80 and 3.57 among African Americans (P < 0.0001
      for race comparison within each biennial cohort). Corresponding hazards ratios,
      adjusted for demographic characteristics and comorbid conditions, were 2.01 (95%
      confidence interval 1.82-2.33), 1.96 (1.78-2.17), 2.00 (1.81-2.20), 2.01 (1.83
      2.21) and 1.86 (1.69-2.04), suggesting the absence of meaningful reduction in
      racial disparities in renal replacement therapy rates over time. CONCLUSION:
      Disparities in renal replacement therapy rates between white and African American
      Medicare beneficiaries have persisted over time.

PMID- 18808389
TI  - Shorter break-in period is a viable option with tighter PD catheter securing
      during the insertion.
AB  - BACKGROUND: Recent single-arm studies reported good catheter outcome despite
      shorter break-in periods after peritoneal dialysis (PD) catheter insertions.
      These results were attributed to tight catheter securing during the insertions.
      OBJECTIVE: To compare catheter-related outcomes after different break-in periods
      in the tightly secured PD catheters. PATIENTS AND METHODS: The study cohort
      comprised 48 patients, who underwent catheter insertions with the modified
      insertion technique. Based on the duration of break-in period, the patients were
      grouped into a shorter break-in period arm, with break-in period of 7 days or
      less and a standard break-in period arm, with break-in period of about 2 weeks.
      Mean patient follow up was 9.68 +/- 4.35 months, with a similar follow-up
      duration between the two break-in period arms (P = 0.94). RESULTS: In the study
      cohort, the incidence of pericatheter leaks, pericatheter haemorrhage, catheter
      malfunction and peritonitis was 2/48 (4%), 1/48 (2%), 1/48 (2%) and 3/48 (6%),
      respectively. There was no other-site leak, bowel perforation, hernia formation
      or wound dehiscence. Of these complications, two pericatheter leaks, one catheter
      malfunction and three peritonitis episodes followed standard break-in periods,
      whereas, one pericatheter haemorrhage occurred in the shorter break-in period
      arm. CONCLUSION: After a tight catheter securing during the insertions, overall
      pericatheter leak incidence remained low in the whole study cohort, and it did
      not worsen despite a shorter break-in period. Future studies with larger patient
      numbers are needed to validate the role of shorter break-in period in PD
      practice.

PMID- 18808390
TI  - Parent-reported adverse food reactions in Hong Kong Chinese pre-schoolers:
      epidemiology, clinical spectrum and risk factors.
AB  - The epidemiology of adverse food reactions (AFRs), including the potentially life
      threatening food allergy (FA), in Asia is unclear. AFR is believed to be less
      prevalent than in Caucasians. This study determines the prevalence, clinical
      features and risk factors for parent-reported AFR in Chinese pre-school children
      in Hong Kong. Children aged 2-7 yr living in Hong Kong were recruited through
      local nurseries and kindergartens to ascertain the occurrence and clinical
      spectrum of AFR and other atopic disorders. Subjects' parents answered a self
      administered questionnaire that was modified and validated based on the
      International Study of Asthma and Allergy in Childhood. A total of 3827 children
      from 21 nurseries and kindergartens returned the study questionnaires, and
      information on AFR was analyzable for 3677 (96.1%) children. The prevalence rates
      of parent-reported AFR and parent-reported, doctor-diagnosed AFR were 8.1% and
      4.6%, respectively, whereas 5.0% of pre-schoolers had doctor-diagnosed asthma.
      The six leading causes of AFR were shellfish (15.8%), egg (9.1%), peanut (8.1%),
      beef (6.4%), cow's milk (5.7%), and tree nuts (5.0%). When compared with children
      born and raised in Hong Kong, children born in mainland China (n = 253) had less
      parent-reported AFR (4.0% vs. 6.7%; p = 0.016). On logistic regression, parent
      reported AFR was associated with younger age (p = 0.010), born in mainland China
      (p = 0.038), and AFR history in father (p = 0.001), mother (p < 0.001), siblings
      (p = 0.020), and paternal history of rhinitis (p = 0.044). This study shows that
      AFR is a common atopic disorder in Hong Kong pre-school children, and prevalence
      rates are comparable to the Caucasians.

PMID- 18808391
TI  - Risky business: perceived behavior of local scientists and community support for
      their research.
AB  - Attracting new technologies to a region can mean significant economic growth, so
      understanding why some communities may not favor becoming "the next Silicon
      Valley" merits consideration. This study investigates the relationship among the
      perceived behavior of local scientists and community members' attitudes toward
      their research. Drawing on theories from organizational justice, it hypothesizes
      that when local residents consider scientists as more just in their behavior,
      they will also have more favorable attitudes toward the scientists and their
      research. Just, in this sense, refers to whether scientists are perceived as fair
      in terms of outcomes, procedures, interpersonal treatment, and explanations in
      their dealings with the community. Favorable attitudes are measured in terms of
      concern about new technologies and satisfaction with research. Data were
      collected via a mail survey of residents in two upstate New York counties (N=
      1,306) that host substantial technology research facilities. Controlling for
      demographics, media use, basic science knowledge, and technology awareness, the
      results show that distributive justice (i.e., fairness of outcomes) had a
      consistent, negative relationship with technology concern. In comparison, all
      four justice variables were positively related with research satisfaction. The
      findings suggest that the perceived behavior of local scientists may indeed
      impact community support for their research.

PMID- 18808392
TI  - A spatial approach to environmental risk assessment of PAH contamination.
AB  - The extent of remediation of contaminated industrial sites depends on spatial
      heterogeneity of contaminant concentration and spatially explicit risk
      characterization. We used sequential Gaussian simulation (SGS) and indicator
      kriging (IK) to describe the spatial distribution of polycyclic aromatic
      hydrocarbons (PAHs), pH, electric conductivity, particle aggregate distribution,
      water holding capacity, and total organic carbon, and quantitative relations
      among them, in a creosote polluted soil in southern Sweden. The geostatistical
      analyses were combined with risk analyses, in which the total toxic equivalent
      concentration of the PAH mixture was calculated from the soil concentrations of
      individual PAHs and compared with ecotoxicological effect concentrations and
      regulatory threshold values in block sizes of 1.8 x 1.8 m. Most PAHs were
      spatially autocorrelated and appeared in several hot spots. The risk calculated
      by SGS was more confined to specific hot spot areas than the risk calculated by
      IK, and 40-50% of the site had PAH concentrations exceeding the threshold values
      with a probability of 80% and higher. The toxic equivalent concentration of the
      PAH mixture was dependent on the spatial distribution of organic carbon, showing
      the importance of assessing risk by a combination of measurements of PAH and
      organic carbon concentrations. Essentially, the same risk distribution pattern
      was maintained when Monte Carlo simulations were used for implementation of risk
      in larger (5 x 5 m), economically more feasible remediation blocks, but a smaller
      area became of great concern for remediation when the simulations included PAH
      partitioning to two separate sources, creosote and natural, of organic matter,
      rather than one general.

PMID- 18808393
TI  - Dealing with the white death: avalanche risk management for traffic routes.
AB  - This article discusses mitigation strategies to protect traffic routes from snow
      avalanches. Up to now, mitigation of snow avalanches on many roads and railways
      in the Alps has relied on avalanche sheds, which require large initial
      investments resulting in high opportunity costs. Therefore, avalanche risk
      managers have increasingly adopted organizational mitigation measures such as
      warning systems and closure policies instead. The effectiveness of these measures
      is, however, greatly dependent on human decisions. In this article, we present a
      method for optimizing avalanche mitigation for traffic routes in terms of both
      their risk reduction impact and their net benefit to society. First, we introduce
      a generic framework for assessing avalanche risk and for quantifying the impact
      of mitigation. This allows for sound cost-benefit comparisons between alternative
      mitigation strategies. Second, we illustrate the framework with a case study from
      Switzerland. Our findings suggest that site-specific characteristics of avalanche
      paths, as well as the economic importance of a traffic route, are decisive for
      the choice of optimal mitigation strategies. On routes endangered by few
      avalanche paths with frequent avalanche occurrences, structural measures are most
      efficient, whereas reliance on organizational mitigation is often the most
      appropriate strategy on routes endangered by many paths with infrequent or fuzzy
      avalanche risk. Finally, keeping a traffic route open may be very important for
      tourism or the transport industry. Hence, local economic value may promote the
      use of a hybrid strategy that combines organizational and structural measures to
      optimize the resource allocation of avalanche risk mitigation.

PMID- 18808394
TI  - International trade inoperability input-output model (IT-IIM): theory and
      application.
AB  - The inoperability input-output model (IIM) has been used for analyzing
      disruptions due to man-made or natural disasters that can adversely affect the
      operation of economic systems or critical infrastructures. Taking economic
      perturbation for each sector as inputs, the IIM provides the degree of economic
      production impacts on all industry sectors as the outputs for the model. The
      current version of the IIM does not provide a separate analysis for the
      international trade component of the inoperability. If an important port of entry
      (e.g., Port of Los Angeles) is disrupted, then international trade inoperability
      becomes a highly relevant subject for analysis. To complement the current IIM,
      this article develops the International Trade-IIM (IT-IIM). The IT-IIM
      investigates the resulting international trade inoperability for all industry
      sectors resulting from disruptions to a major port of entry. Similar to
      traditional IIM analysis, the inoperability metrics that the IT-IIM provides can
      be used to prioritize economic sectors based on the losses they could potentially
      incur. The IT-IIM is used to analyze two types of direct perturbations: (1) the
      reduced capacity of ports of entry, including harbors and airports (e.g., a
      shutdown of any port of entry); and (2) restrictions on commercial goods that
      foreign countries trade with the base nation (e.g., embargo).

PMID- 18808395
TI  - Parameters of a dose-response model are on the boundary: what happens with BMDL?
AB  - It is well known that, under appropriate regularity conditions, the asymptotic
      distribution for the likelihood ratio statistic is chi(2). This result is used in
      EPA's benchmark dose software to obtain a lower confidence bound (BMDL) for the
      benchmark dose (BMD) by the profile likelihood method. Recently, based on work by
      Self and Liang, it has been demonstrated that the asymptotic distribution of the
      likelihood ratio remains the same if some of the regularity conditions are
      violated, that is, when true values of some nuisance parameters are on the
      boundary. That is often the situation for BMD analysis of cancer bioassay data.
      In this article, we study by simulation the coverage of one- and two-sided
      confidence intervals for BMD when some of the model parameters have true values
      on the boundary of a parameter space. Fortunately, because two-sided confidence
      intervals (size 1-2alpha) have coverage close to the nominal level when there are
      50 animals in each group, the coverage of nominal 1-alpha one-sided intervals is
      bounded between roughly 1-2alpha and 1. In many of the simulation scenarios with
      a nominal one-sided confidence level of 95%, that is, alpha= 0.05, coverage of
      the BMDL was close to 1, but for some scenarios coverage was close to 90%, both
      for a group size of 50 animals and asymptotically (group size 100,000). Another
      important observation is that when the true parameter is below the boundary, as
      with the shape parameter of a log-logistic model, the coverage of BMDL in a
      constrained model (a case of model misspecification not uncommon in BMDS
      analyses) may be very small and even approach 0 asymptotically. We also discuss
      that whenever profile likelihood is used for one-sided tests, the Self and Liang
      methodology is needed to derive the correct asymptotic distribution.

PMID- 18808396
TI  - Understanding consumer attitudes toward food technologies in Canada.
AB  - This article reports a study on consumer attitudes to 21 food and nonfood
      technologies in Canada. The study involves repertory grid interviews with 36 food
      consumers, the data from which are analyzed using generalized Procrustes
      analysis. Results highlight the role of perceived risk and perceived benefit in
      determining the acceptability of the technologies, with individual technologies
      lying along a continuum between the two. For technology as a whole and the 21
      specific technologies, the perceived risk and perceived benefit constructs were
      the dominant determinants of consumer acceptability. While perceptions of
      perceived risk and perceived benefit differed between individual respondents,
      there were very limited consistent relations with a range of sociodemographic
      variables.

PMID- 18808397
TI  - Exposure assessment for pesticide intake from multiple food products: a Bayesian
      latent-variable approach.
AB  - Pesticide risk assessment for food products involves combining information from
      consumption and concentration data sets to estimate a distribution for the
      pesticide intake in a human population. Using this distribution one can obtain
      probabilities of individuals exceeding specified levels of pesticide intake. In
      this article, we present a probabilistic, Bayesian approach to modeling the daily
      consumptions of the pesticide Iprodione though multiple food products. Modeling
      data on food consumption and pesticide concentration poses a variety of problems,
      such as the large proportions of consumptions and concentrations that are
      recorded as zero, and correlation between the consumptions of different foods. We
      consider daily food consumption data from the Netherlands National Food
      Consumption Survey and concentration data collected by the Netherlands Ministry
      of Agriculture. We develop a multivariate latent-Gaussian model for the
      consumption data that allows for correlated intakes between products. For the
      concentration data, we propose a univariate latent-t model. We then combine
      predicted consumptions and concentrations from these models to obtain a
      distribution for individual daily Iprodione exposure. The latent-variable models
      allow for both skewness and large numbers of zeros in the consumption and
      concentration data. The use of a probabilistic approach is intended to yield more
      robust estimates of high percentiles of the exposure distribution than an
      empirical approach. Bayesian inference is used to facilitate the treatment of
      data with a complex structure.

PMID- 18808398
TI  - Insulin sensitivity, VO2max and body composition in severely obese Swedish
      children and adolescents.
AB  - AIM: The aim of this study was to identify relationships between insulin
      sensitivity (SI), cardiorespiratory fitness and body composition in severely
      obese Swedish children and adolescents. METHODS: Two hundred and twenty-eight
      obese children (119 girls, 8-16 years, body mass index (BMI) 23.2-57.0 kg/m(2))
      performed a frequently sampled intravenous glucose tolerance test (FSIVGTT), a
      submaximal bicycle ergometry test and a dual-energy X-ray absorptiometry (DEXA).
      RESULTS: Mean SI (SD) was 0.38 (0.32) (x10(-5)/min/pM). SI correlated positively
      with relative body mass (BM) VO(2)max (r = 0.42) (p < 0.001), relative fat-free
      mass (FFM) VO(2)max (r = 0.36) (p < 0.001) and negatively with body mass index
      standard deviation score (BMI SDS) (r =-0.22) (p = 0.001). SI did not correlate
      with percent body fat (r =-0.01) and absolute VO(2)max (r = 0.01). In multiple
      regression analyses with SI as dependent variable, VO(2)max and body composition,
      together with gender, age and Tanner stage, explained 20-26% of the variance.
      CONCLUSION: Relative (BM) VO(2)max and relative (FFM) VO(2)max were stronger
      predictors of SI than percent body fat in severely obese children and
      adolescents. The study confirms that cardiorespiratory fitness is of importance
      for the metabolic syndrome in the studied population. Efforts to improve SI
      should include physical activity targeting cardiorespiratory fitness also in
      severely obese children and adolescents.

PMID- 18808399
TI  - Ludwig II, King of Bavaria: a royal medical history.
AB  - OBJECTIVE: The case of Ludwig II, King of Bavaria, had soon become synonymous
      with paranoia, after he had drowned at the age of 40 together with the
      neuropsychiatrist Gudden. METHOD: We were granted access to the Secret Archive of
      the House of Wittelsbach to study documents on Ludwig's medical history. RESULTS:
      The documents underlying Gudden's expert opinion which led to Ludwig being
      deposed would be insufficient for a diagnosis of schizophrenia according to
      contemporary standards. The autopsy revealed prominent prefrontal brain atrophy.
      CONCLUSION: The evidence is compatible with a diagnosis of schizotypal
      personality and suspected frontotemporal degeneration.

PMID- 18808400
TI  - Adjunctive lithium treatment in the prevention of suicidal behaviour in
      depressive disorders: a randomised, placebo-controlled, 1-year trial.
AB  - OBJECTIVE: Evidence based on controlled studies is still limited for treatment
      strategies that prevent recurrence of suicide attempts. Findings from
      observational as well as meta-analytic studies strongly suggest that lithium may
      have suicide-protective properties. METHOD: Patients with a recent suicide
      attempt in the context of an affective spectrum disorder (n = 167) were treated
      with either lithium or placebo during a 12-month period. RESULTS: Survival
      analysis showed no significant difference of suicidal acts between lithium and
      placebo-treated individuals (adjusted hazard ratio 0.517; 95% CI 0.18-1.43).
      However, post hoc analysis revealed that all completed suicides had occurred in
      the placebo group accounting for a significant difference in incidence rates (P =
      0.049). CONCLUSION: Results indicate that lithium treatment might be effective in
      reducing the risk of completed suicide in adult patients with affective
      disorders. Our findings contribute to the growing body of evidence suggesting a
      specific antisuicidal effect of lithium.

PMID- 18808401
TI  - COMT ValMet moderation of cannabis-induced psychosis: a momentary assessment
      study of 'switching on' hallucinations in the flow of daily life.
AB  - OBJECTIVE: A functional polymorphism in the catechol-o-methyltransferase gene
      (COMT Val(158)Met) may moderate the psychosis-inducing effects of cannabis. In
      order to extend this finding to dynamic effects in the flow of daily life, a
      momentary assessment study of psychotic symptoms in response to cannabis use was
      conducted. METHOD: The experience sampling technique was used to collect data on
      cannabis use and occurrence of symptoms in daily life in patients with a
      psychotic disorder (n = 31) and healthy controls (n = 25). RESULTS: Carriers of
      the COMT Val(158)Met Val allele, but not subjects with the Met/Met genotype,
      showed an increase in hallucinations after cannabis exposure, conditional on
      prior evidence of psychometric psychosis liability. CONCLUSION: The findings
      confirm that in people with psychometric evidence of psychosis liability, COMT
      Val(158)Met genotype moderates the association between cannabis and psychotic
      phenomena in the flow of daily life.

PMID- 18808402
TI  - Proceedings of Consensus Conference on Simultaneous Liver Kidney Transplantation
      (SLK).
AB  - A consensus conference sponsored by the American Society of Transplant Surgeons
      (ASTS), American Society of Transplantation (AST), United Network for Organ
      Sharing (UNOS) and American Society of Nephrology (ASN) convened to examine
      simultaneous liver-kidney transplantation (SLK). Directors from the 25 largest
      liver transplant programs along with speakers with recognized expertise attended.
      The purposes of this conference were to propose indications for SLK, to establish
      a prospective data registry and, most importantly, to recommend standard listing
      criteria for these patients. Scientific registry of transplant recipients data,
      and single center data regarding chronic kidney disease (CKD) and acute kidney
      injury (AKI) in conjunction with liver failure as a basis for SLK was presented
      and discussed. The consensus was that Regional Review Boards (RRB) should
      determine listing for SLK, as with other MELD exceptions, with automatic approval
      for: (i) End-stage renal disease with cirrhosis and symptomatic portal
      hypertension or hepatic vein wedge pressure gradient >/= 10 mm Hg (ii) Liver
      failure and CKD with GFR </= 30 mL/min (iii) AKI or hepatorenal syndrome with
      creatinine >/= 2.0 mg/dL and dialysis >/= 8 weeks (iv) Liver failure and CKD and
      biopsy demonstrating > 30% glomerulosclerosis or 30% fibrosis. The RRB would
      evaluate all other requests to determine appropriateness.

PMID- 18808403
TI  - Neighborhood poverty and kidney transplantation among US Asians and Pacific
      Islanders with end-stage renal disease.
AB  - The degree to which low transplant rates among Asians and Pacific Islanders in
      the United States are confounded by poverty and reduced access to care is
      unknown. We examined the relationship between neighborhood poverty and kidney
      transplant rates among 22 152 patients initiating dialysis during 1995-2003
      within 1800 ZIP codes in California, Hawaii and the US-Pacific Islands. Asians
      and whites on dialysis were distributed across the spectrum of poverty, while
      Pacific Islanders were clustered in the poorest areas. Overall, worsening
      neighborhood poverty was associated with lower relative rates of transplant
      (adjusted HR [95% CI] for areas with > or =20% vs. <5% residents living in
      poverty, 0.41 [0.32-0.53], p < 0.001). At every level of poverty, Asians and
      Pacific Islanders experienced lower transplant rates compared with whites. The
      degree of disparity increased with worsening neighborhood poverty (adjusted HR
      [95% CI] for Asians-Pacific Islanders vs. whites, 0.64 [0.51-0.80], p < 0.001 for
      areas with <5% and 0.30 [0.21-0.44], p < 0.001 for areas with > or =20% residents
      living in poverty; race-poverty level interaction, p = 0.039). High levels of
      neighborhood poverty are associated with lower transplant rates among Asians and
      Pacific Islanders compared with whites. Our findings call for studies to identify
      cultural and local barriers to transplant among Asians and Pacific Islanders,
      particularly those residing in resource-poor neighborhoods.

PMID- 18808404
TI  - A randomized, prospective trial of rituximab for acute rejection in pediatric
      renal transplantation.
AB  - We report 1-year outcomes of a randomized study of Rituximab versus standard-of
      care immunosuppression (Thymoglobulin and/or pulse steroids) for treatment of
      biopsy confirmed, acute transplant rejection with B-cell infiltrates, in 20
      consecutive recipients (2-23 years). Graft biopsies, with Banff and CADI scores,
      CD20 and C4d stains, were performed at rejection and 1 and 6 months later.
      Peripheral blood CMV, EBV and BK viral loads, graft function, DSA,
      immunoglobulins, serum humanized antichimeric antibody (HACA) and Rituximab, and
      lymphocyte counts were monitored until 1 year posttreatment. Rituximab infusions
      were given with a high index of safety without HACA development and increased
      infections complications. Rituximab therapy resulted in complete tissue B-cell
      depletion and rapid peripheral B-cell depletion. Peripheral CD19 cells recovered
      at a mean time of approximately 12 months. There were some benefits for the
      recovery of graft function (p = 0.026) and improvement of biopsy rejection scores
      at both the 1- (p = 0.0003) and 6-month (p < 0.0001) follow-up biopsies.
      Reappearance of C4d deposition was not seen on follow-up biopsies after Rituximab
      therapy, but was seen in 30% of control patients. There was no change in DSA in
      either group, independent of rejection resolution. This study reports safety and
      suggests further investigation of Rituximab as an adjunctive treatment for B-cell
      mediated graft rejection.

PMID- 18808405
TI  - Survival advantage of pediatric recipients of a first kidney transplant among
      children awaiting kidney transplantation.
AB  - The mortality rate in children with ESRD is substantially lower than the rate
      experienced by adults. However, the risk of death while awaiting kidney
      transplantation and the impact of transplantation on long-term survival has not
      been well characterized in the pediatric population. We performed a longitudinal
      study of 5961 patients under age 19 who were placed on the kidney transplant
      waiting list in the United States. Of these, 5270 received their first kidney
      transplant between 1990 and 2003. Survival was assessed via a time-varying
      nonproportional hazards model adjusted for potential confounders. Transplanted
      children had a lower mortality rate (13.1 deaths/1000 patient-years) compared to
      patients on the waiting list (17.6 deaths/1000 patient-years). Within the first 6
      months of transplant, there was no significant excess in mortality compared to
      patients remaining on the waiting list (adjusted Relative Risk (aRR) = 1.01; p =
      0.93). After 6 months, the risk of death was significantly lower: at 6-12 months
      (aRR = 0.37; p < 0.001) and at 30 months (aRR 0.26; p < 0.001). Compared to
      children who remain on the kidney transplant waiting list, those who receive a
      transplant have a long-term survival advantage. With the potential for unmeasured
      bias in this observational data, the results of the analysis should be
      interpreted conservatively.

PMID- 18808406
TI  - Severe left ventricular systolic dysfunction may reverse with renal
      transplantation: uremic cardiomyopathy and cardiorenal syndrome.
AB  - Chronic heart failure (CHF) and chronic kidney disease (CKD) are serious medical
      conditions with significant morbidity and mortality. Emerging evidence indicates
      that the function of these two organ systems are affected by each other in a
      complex interplay. Most patients with CKD suffer frequently from cardiac
      abnormalities including left ventricular hypertrophy (LVH), left ventricular
      dilatation (LVD), left ventricular (LV) diastolic and/or systolic dysfunction.
      Although previously thought that LV systolic dysfunction was an absolute
      contraindication to renal transplantation, several observational studies have
      shown this not to be true and that transplantation can lead to significant
      improvement in LV systolic function. Furthermore, correction of the uremic state
      by renal transplantation leads to improvement of LVD and possibly regression of
      LVH. In fact, the reduction of LVH postkidney transplantation was shown to be
      dependent on adequate renal function and hypertension control. Diabetes mellitus
      does not seem to be a confounding factor in the improvement of uremic
      cardiomyopathy with renal transplantation.

PMID- 18808407
TI  - Intentional ABO-incompatible lung transplantation.
AB  - We report on a case of intentional blood group incompatible lung transplantation.
      A blood group O cystic fibrosis patient was mechanically ventilated and put on
      interventional lung assist for severe respiratory decompensation. Since timely
      allocation of a blood group O donor lung was impossible, an AB deceased donor
      lung rescue allocation was accepted and the transplant performed using a pre-,
      peri- and postoperative antibody depletion protocol including plasmapheresis,
      ivIg administration, rituximab and immunoadsorption. Nine months after the
      transplant the patient is at home and well.

PMID- 18808408
TI  - Prolonged insulin independence after islet allotransplants in recipients with
      type 1 diabetes.
AB  - We sought to determine the long-term outcomes in type 1 diabetic recipients of
      intraportal alloislet transplants on a modified immunosuppressive protocol. Six
      recipients with hypoglycemia unawareness received one to two islet infusions.
      Induction therapy was with antithymocyte globulin (ATG) plus etanercept for tumor
      necrosis factor-alpha blockade. Recipients received cyclosporine and everolimus
      for maintenance immunosuppression for the first year posttransplant, with
      mycophenolic acid or mycophenolate mofetil subsequently substituted for
      everolimus. Recipients have been followed for 1173 +/- 270 days since their last
      infusion for islet graft function (insulin independence, hemoglobin A(1c) levels
      and C-peptide production) and for adverse events associated with the study
      protocol. Of the six recipients, five were insulin-independent at 1 year, and
      four continue to be insulin-independent at a mean of 3.4 +/- 0.4 years
      posttransplant. None of the six recipients experienced recurrence of severe
      hypoglycemia. Measured glomerular filtration rate decreased from 110.5 +/- 21.2
      mL/min/1.73 m(2) pretransplant to 82.6 +/-19.1 mL/min/1.73 m(2) at 1 year
      posttransplant. In conclusion, islet transplants restored insulin independence
      for a mean of >3 years in four of six recipients treated with ATG and etanercept
      induction therapy and with cyclosporine and, initially, everolimus for
      maintenance. Our results suggest this immunosuppressive protocol may allow long
      term graft survival.

PMID- 18808409
TI  - Monozygotic transplantation: concerns and opportunities.
AB  - We describe the case of a 24-year-old female with end-stage renal disease from
      focal segmental glomerulosclerosis (FSGS) diagnosed at age 16, who underwent
      monozygotic triplet transplantation at age 21 from her sister. Monozygosity was
      established by buccal smear DNA PCR amplification using short tandem repeat (1)
      profiling for 16 genetic alleles. All immunosuppression was discontinued by 1
      month posttransplant. To evaluate the use of immunosuppression in HLA identical
      monozygotic transplantation, we interrogated the OPTN (Organ Procurement
      Transplant Network) database for all transplants conducted from 1987 to 2006. We
      identified 194 probable identical twin transplantations based on age, gender,
      race, ethnic category, blood type and HLA match. We evaluated the use of various
      immunosuppressive agents at discharge, 6 months and 1, 2 and 3 years after
      transplantation. Seventy-one percent of these patients at discharge and 34% at
      the end of 1 year were on immunosuppression. At discharge 61% received steroids
      and 30% received calcineurin inhibitors and 66% of these remained on calcineurin
      inhibitors at 1 year. Renal function was superior among those not maintained on
      immunosuppression. Thus, monozygotic transplantation confers an immunologic
      advantage that allows immunosuppression elimination despite a risk of recurrent
      glomerular disease such as FSGS with appropriate evaluation and management.

PMID- 18808410
TI  - Does a nerve-sparing technique or potency affect continence after open radical
      retropubic prostatectomy?
AB  - OBJECTIVE: To characterize the effect of preserving the neurovascular bundle
      (NVB) and of potency on urinary continence after open radical retropubic
      prostatectomy (ORRP). PATIENTS AND METHODS: Between October 2000 to September
      2005, 1110 consecutive continent men had ORRP by one surgeon. The University of
      California Los Angeles Prostate Cancer Index was self-administered at baseline
      and 3, 6, 12, and 24 months after ORRP. Men were considered continent if they
      responded that they had total urinary control or had occasional urinary leakage.
      Men were considered potent if they engaged in sexual intercourse with or without
      the use of phosphodiesterase inhibitors at least once in the month before or
      after ORRP. Of the 1110 men, 728 (66%) were potent and continent at baseline. Men
      undergoing adjuvant hormonal therapy, radiation therapy or chemotherapy were
      excluded. The potency status was evaluated in 610 men at 24 months after ORRP,
      and the number of NVBs preserved was recorded at the time of ORRP. RESULTS: Of
      men who were potent at baseline and had bilateral vs unilateral nerve sparing,
      96% and 99% were continent at 24 months, respectively (P = 0.50). Of the men who
      were potent and impotent at 24 months, 98% and 96% were continent at 24 months,
      respectively (P = 0.25). Continence did not depend on whether men regained
      potency or whether they had a bilateral or a unilateral nerve-sparing procedure.
      CONCLUSION: Our observation that only 60% of men undergoing bilateral nerve
      sparing ORRP regain potency suggests that the NVBs are often inadvertently
      injured, despite efforts to preserve them. We feel that potency status is the
      best indicator of the true extent of NVB preservation. That men undergoing
      bilateral vs unilateral nerve-sparing procedures, and that potent vs impotent men
      at 24 months have similar continence rates, provides compelling evidence that
      nerve-sparing is not associated with better continence. Based on these findings,
      NVBs should not be preserved in men with baseline erectile dysfunction, with the
      expectation of improving continence.

PMID- 18808411
TI  - Cutaneous infection due to Mycobacterium interjectum in an immunosuppressed
      patient with microscopic polyangiitis.

PMID- 18808412
TI  - Biologic therapies for psoriasis: practical experience in a U.K. tertiary
      referral centre.
AB  - BACKGROUND: Large-scale clinical trials provide clear evidence of the efficacy
      and short-term toxicity of biologic therapies for psoriasis. However, to date,
      there are few reports of the practical use of these therapies outside of the
      trial setting and, to our knowledge, none from a U.K. cohort of patients with
      psoriasis. OBJECTIVES: (i) To assess efficacy and safety of efalizumab,
      etanercept and infliximab in a U.K. cohort of patients with psoriasis, with mean
      Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index 21.8
      and 21.7, respectively, outside of the clinical trial setting. (ii) To examine
      our approach to the processes involved in the initiation of biologic therapies in
      the era of National Institute for Health and Clinical Excellence guidance.
      METHODS: A retrospective case-note review to identify all patients initiated on
      biologic therapies for psoriasis in a U.K. tertiary referral centre. RESULTS: At
      3 months of treatment the efficacy of efalizumab (n = 28), etanercept (n = 70)
      and infliximab (n = 20), as assessed by PASI 75 (75% decrease from baseline
      score), was 24%, 35% and 85%, respectively. All three biologics used were well
      tolerated. Combination therapy with traditional systemic agents was required
      either at transition to, or to counter relapse while established on, a biologic
      therapy in 30% of cases. Streamlined approaches to screening and funding
      significantly (P </= 0.05) hastened the initiation of biologic therapies.
      CONCLUSIONS: In a cohort of U.K. patients with severe psoriasis, biologic
      therapies have proved to be a significant step forward in expanding the
      therapeutic armamentarium for psoriasis. Pharmacovigilance, in the form of
      registries, is essential to assess the long-term safety of such drugs.

PMID- 18808413
TI  - Economic evaluation of etanercept in the management of chronic plaque psoriasis.
AB  - BACKGROUND: The National Institute for Health and Clinical Excellence has
      recommended that etanercept 25 mg twice weekly (biw) be used in adults with
      severe plaque psoriasis. However, its economic model did not consider the
      alternative licensed regimen of etanercept 50 mg biw. OBJECTIVES: To assess the
      cost-effectiveness of etanercept 50 mg biw for the treatment of chronic plaque
      psoriasis, and to explore characteristics of patients who benefited most from 50
      mg dosing. METHODS: An economic model was constructed to estimate the incremental
      cost per quality-adjusted life year (QALY) gained. The model considered patients
      with chronic plaque psoriasis who had both Psoriasis Area and Severity Index
      (PASI) and Dermatology Life Quality Index (DLQI) of 10 or higher who were unable
      to take standard systemic therapies. Quality of life gain was estimated from the
      DLQI responses of patients enrolled in three clinical studies. The model
      considered expenditure on drugs, monitoring visits, adverse events and inpatient
      stays. Costs were estimated from the perspective of the U.K. National Health
      Service over a time period of 10 years. RESULTS: The incremental cost per QALY
      for etanercept 50 mg biw compared with no systemic therapy was found to be 6217
      pounds sterling (95% confidence interval 5396-7486 pounds sterling). The cost
      effectiveness of 50 mg dosing was more attractive in patients with baseline PASI
      > or = 20 (5163 pounds sterling) or baseline DLQI > or = 20 (4599 pounds
      sterling). CONCLUSIONS: This model found the licensed dose regimen of etanercept
      50 mg biw to be cost effective in the U.K. This regimen was particularly
      appropriate for patients with severe disease or poor quality of life at baseline.

PMID- 18808414
TI  - Function of oleic acid on epidermal barrier and calcium influx into keratinocytes
      is associated with N-methyl D-aspartate-type glutamate receptors.
AB  - BACKGROUND: Unsaturated fatty acids from sebum affect calcium dynamics in
      epidermal keratinocytes, disrupt the barrier function and induce abnormal
      keratinization. However, the mechanisms of these effects have not been clarified.
      OBJECTIVES: To investigate the function of unsaturated fatty acids in epidermis.
      METHODS: Antagonists of calcium channel receptors were applied to mouse skin
      together with oleic acid. Measurements were made of transepidermal water loss
      (TEWL), and hyperproliferation was assessed. The effects of the antagonists on
      calcium influx into cultured normal human keratinocytes and on cytokine
      production were also evaluated. RESULTS: N-methyl-d-aspartate (NMDA) receptor
      antagonists such as MK801 and D-AP5 specifically inhibited the increase in TEWL
      caused by oleic acid, and suppressed keratinocyte hyperproliferation. These
      compounds also inhibited the increase in the intracellular concentration of
      calcium ions induced by oleic acid. MK801 suppressed the production of
      interleukin-1alpha by keratinocytes induced by oleic acid. CONCLUSIONS:
      Unsaturated fatty acids such as oleic acid might function via NMDA receptors.

PMID- 18808415
TI  - Whither... the future for contact dermatitis? A report from the 2007
      International Review of Current Problems in Contact Dermatitis.
AB  - In our report we summarize presentations made at the International Review of
      Current Problems in Contact Dermatitis meeting which took place at the St John's
      Institute of Dermatology, London, on 1 June 2007, and which brought together over
      100 dermatologists from the U.K., continental Europe and the U.S.A. During this
      small and informal meeting, the state-of-the art lectures on various aspects of
      contact dermatitis were followed by energetic discussions.

PMID- 18808416
TI  - IgE autoantibodies against the intracellular domain of BP180.
AB  - BACKGROUND: Bullous pemphigoid (BP) is an autoimmune subepidermal blistering
      disease characterized by autoantibodies against the hemidesmosomal proteins BP180
      (type XVII collagen) and BP230. BP not only involves IgG-mediated neutrophil
      activation, leading to blistering, but also IgE-dependent activation of mast
      cells and basophils. While IgG and IgE autoantibodies target the extracellular
      noncollagenous (NC) 16A domain of BP180, little is known whether other BP180
      regions are targeted by these antibody classes. OBJECTIVES: To characterize IgE
      and IgG autoantibody binding to antigenic sites on the intracellular domain (ICD)
      of BP180 compared with BP180 NC16A. METHODS: IgE/IgG autoreactivity against
      recombinant BP180 ICD and NC16A was determined by immunoblotting of sera from 18
      patients with BP and 10 controls. RESULTS: Total serum IgE was elevated in 16 of
      18 BP sera. Most BP sera tested positive (15 of 18) to NC16A with both
      immunoglobulin classes. Additionally, 14 of 18 sera showed IgE reactivity with an
      epitope mapped to the ICD of BP180 (amino acid residues 103-266). Mapping of ICD
      antigenic sites revealed similar IgE and IgG reactivities for most regions except
      for greater IgE reactivity to amino acid residues 234-398 (11 of 18 BP sera) than
      IgG (five of 18). Control sera failed to display IgE reactivity to these
      antigens. CONCLUSIONS: The results indicate that BP180 NC16A is not the only
      antigenic determinant of IgE autoantibodies in BP and that additional, novel
      epitopes exist on different regions of the ICD of BP180. The heterogeneous
      autoimmune response against BP180 suggests intramolecular epitope spreading
      during disease progression.

PMID- 18808417
TI  - Development of squamous cell carcinomas in Darier disease: a new model for skin
      carcinogenesis?

PMID- 18808418
TI  - Topical treatment for human papillomavirus-associated genital warts in humans
      with the novel tellurium immunomodulator AS101: assessment of its safety and
      efficacy.
AB  - BACKGROUND: Various methods are currently used for the treatment of anogenital
      warts. However, a complete cure is unlikely, and the rate of recurrence is high.
      OBJECTIVES: The purpose of this open-label, multicentre trial was to evaluate the
      safety and clinical efficacy of a new treatment using the immunomodulator
      ammonium trichloro (dioxoethylene-O,O') tellurate (AS101; Biomas Ltd, Kefar Saba,
      Israel) 15% w/w cream to clear vulval/perianal condylomata acuminata. METHODS:
      Study participants comprised 48 women and 26 men, age range 18-62 years. Of the
      48 woman, 44 were diagnosed with vulval condylomata and four with perianal
      condylomata. All 26 men were diagnosed with perianal condylomata. All the
      patients in the study received AS101 15% w/w cream twice a day. Maximal treatment
      duration was 16 weeks. To evaluate the safety and clinical efficacy, patients
      were examined and lesional areas photographed on a biweekly basis. RESULTS: By
      the end of the treatment, 56 of 74 (76%) patients were considered completely
      cleared. Complete cure was achieved in 35 of 44 (80%) patients with vulval
      condylomata and in 21 of 30 (70%) patients with perianal condylomata. No scarring
      of treated areas was observed. Complete cure was achieved within a time range of
      10-109 days. The most frequent side-effects observed were mild-to-moderate
      itching, soreness, burning and erythema. In post-treatment follow up of up to 6
      months, disease recurrence was observed in two patients (4%), at 105 and 144 days
      following completion of treatment. CONCLUSIONS: AS101 15% w/w cream is an
      effective and safe, self-administered therapy used for the treatment of external
      vulval and perianal warts. The cream is applied topically twice daily for up to
      16 weeks. A very low recurrence rate was reported.

PMID- 18808419
TI  - Incidence of primary cutaneous T-cell lymphoma in Norway.
AB  - BACKGROUND: Studies from different countries have reported an increased incidence
      of primary cutaneous lymphomas over the last decades. OBJECTIVES: To estimate the
      incidence rates of primary cutaneous T-cell lymphoma (CTCL) and mycosis fungoides
      (MF)/Sezary syndrome (SS) in Norway, and to compare these rates with those
      reported from other countries. METHODS: Data from the Cancer Registry of Norway
      on non-Hodgkin lymphomas during the period 1980-2003 were analysed. RESULTS: In
      total, 337 cases of CTCL were reported to the Cancer Registry during the study
      period, of which 262 cases were classified as MF/SS. The incidence rate of CTCL
      increased significantly (P(trend) < 0.001) from 0.16 (95% confidence interval, CI
      0.11-0.20) per 100,000 person-years in 1980-84 to 0.29 (95% CI 0.22-0.36) per
      100,000 person-years in 2000-2003. The incidence of MF/SS also increased during
      the same period (P(trend) = 0.05) from 0.15 (95% CI 0.10-0.19) per 100,000 person
      years to 0.18 (95% CI 0.13-0.24) per 100,000 person-years. CONCLUSIONS: The
      incidence of both CTCL and MF/SS increased in Norway during the period 1980-2003.

PMID- 18808420
TI  - Regulation of TGF-beta family signaling by E3 ubiquitin ligases.
AB  - Members of the transforming growth factor-beta (TGF-beta) family, including TGF
      beta, activin and bone morphogenetic proteins (BMPs), are multifunctional
      proteins that regulate a wide variety of cellular responses, such as
      proliferation, differentiation, migration and apoptosis. Alterations in their
      downstream signaling pathways are associated with a range of human diseases like
      cancer. TGF-beta family members transduce signals through membrane
      serine/threonine kinase receptors and intracellular Smad proteins. The ubiquitin
      proteasome pathway, an evolutionarily conserved cascade, tightly regulates TGF
      beta family signaling. In this pathway, E3 ubiquitin ligases play a crucial role
      in the recognition and degradation of target proteins by the 26S proteasomes.
      Smad degradation regulates TGF-beta family signaling; HECT (homologous to the E6
      accessory protein C-terminus)-type E3 ubiquitin ligases, Smad ubiquitin
      regulatory factor 1 (Smurf1), Smurf2, and a RING-type E3 ubiquitin ligase, ROC1
      SCF(Fbw1a) have been implicated in Smad degradation. Smurf1 and Smurf2 bind to
      TGF-beta family receptors via the inhibitory Smads, Smad6 and Smad7, to induce
      their ubiquitin-dependent degradation. Arkadia, a RING-type E3 ubiquitin ligase,
      induces the ubiquitination and degradation of Smad7 and corepressors, c-Ski and
      SnoN, to enhance TGF-beta family signaling. Abnormalities in E3 ubiquitin ligases
      that control components of TGF-beta family signaling may lead to the development
      and progression of various cancers.

PMID- 18808421
TI  - p27(Kip1)is overexpressed in very early stages of hepatocarcinogenesis.
AB  - Hepatocellular carcinoma (HCC) associated with chronic liver disease evolves from
      precancerous lesions and early HCC to more malignant forms. Despite the
      demonstrated importance of cell-cycle regulators in tumor biology, there have
      been few studies of their role in multistep hepatocarcinogenesis. Expression of
      p27(Kip1) and a degradation pathway associated protein, S-phase kinase
      interacting protein 2 (Skp2), was therefore evaluated in surgically resected
      specimens of eight adenomatous hyperplasias, 16 early HCC and 126 classical HCC.
      Immunohistochemistry revealed no p27(Kip1) expression in the majority of
      hepatocytes from normal and cirrhotic liver, whereas positive staining for
      p27(Kip1) protein was found in 75.0% and 93.8% of adenomatous hyperplasias and
      early HCC, respectively. The average p27(Kip1) labeling indices (LI) for
      adenomatous hyperplasias, early HCC, well differentiated HCC, moderately
      differentiated HCC and poorly differentiated HCC were 36.99, 43.59, 47.73, 49.24,
      and 30.21, respectively. Real-time quantitative reverse transcription-polymerase
      chain reaction (RT-PCR) analyses confirmed the increases. Skp2 LI were also
      significantly elevated in accordance with stepwise progression of
      hepatocarcinogenesis. Increased expression of Skp2 mRNA was observed most
      frequently in less differentiated tumors and Kaplan-Meier survival analysis
      showed a significantly association with a poor prognosis (P = 0.0496). In
      conclusion, a high level of p27(Kip1) expression is evident from early stages of
      hepatocarcinogenesis, indicating that this parameter could be a useful diagnostic
      marker for precancerous lesions and early HCC. In addition, Skp2 expression
      correlates with tumor dedifferentiation and may contribute to biological
      aggression in HCC.

PMID- 18808422
TI  - Sensitivity of a Giardia antigen test in persistent giardiasis following an
      extensive outbreak.
AB  - The utility of a rapid antigen test for diagnosing cases of persistent
      giardiasis, as defined by detection of cysts by conventional microscopy following
      standard formalin-ether concentration or the positive rapid antigen test, was
      investigated following a large, waterborne outbreak of giardiasis. The
      sensitivity and specificity of the rapid test as compared with microscopy were
      60.7% and 96.7%, respectively, in this patient group. The low sensitivity
      contrasts with previous reports, and may be partly explained by low cyst numbers.

PMID- 18808423
TI  - Community-associated Staphylococcus aureus infections and nasal carriage among
      children: molecular microbial data and clinical characteristics.
AB  - An increasing number of infections caused by community-associated methicillin
      resistant Staphylococcus aureus (CA-MRSA) carrying the Panton-Valentine
      leukocidin (PVL) genes was recently identified in Greece. In the present study,
      170 patients with S. aureus infections and 123 uninfected children (<15 years
      old) who had been tested for nasal carriage were evaluated during a 2-year
      period. The MecA, PVL and superantigen family genes, and MRSA clones, were
      investigated by molecular methods. Sites of infection and laboratory findings for
      patients were recorded. The results were compared and statistically analysed.
      Among 123 uninfected children 73 (59%) carried S. aureus, including four MRSA
      strains. Of these, three MRSA and three methicillin-sensitive S. aureus (MSSA)
      strains were PVL-positive (p <0.0001). Ninety-six patients (96/170) exhibited
      skin and soft-tissue infections (SSTIs), and 74 exhibited invasive infections.
      The incidence of staphylococcal infections increased during July to September
      each year. In total, 110 S. aureus isolates were PVL-positive (81 from SSTIs and
      29 from invasive infections, p <0.0001). Ninety-nine out of 106 MRSA (93%)
      isolates from 170 patients carried the PVL genes (p <0.0001); 97 belonged to the
      clonal complex CC80. Leukocyte and polymorphonuclear cell counts were higher
      among children with MRSA infections (p <0.005). MSSA predominated among patients
      with invasive infections (43/74), and carried mainly genes of the superantigen
      family. Children <5 years of age showed a higher risk of MRSA infection. The
      present study demonstrates that infections due to PVL-positive CA-MRSA spread
      easily among children, and SSTIs can lead to invasive infections. Nasal
      colonization may be an additional factor contributing to the emergence of CA
      MRSA.

PMID- 18808424
TI  - Levetiracetam in absence epilepsy.
AB  - The aim of the study was to assess the efficacy, tolerability, and safety of
      levetiracetam therapy in children and adolescents with absence epilepsy. Twenty
      one participants (11 male, 10 female) with typical absence seizures were enrolled
      in this prospective study from seven centres in Italy. The mean age and age range
      at time of enrollment into the study were 8 years 9 months (SD 0.9) and 5 years 1
      month to 13 years respectively. All patients were carefully evaluated at 6 months
      from baseline, and 12 patients were also re-evaluated at 12 months after the
      beginning of therapy with levetiracetam. At the 6-month evaluation, out of 21
      patients studied, 11 were seizure free and one showed 'decreased' seizures (more
      than 50% reduction in seizures). A less than 50% reduction in seizures was
      observed in nine patients. At the 12-month evaluation, 10 patients were
      completely seizure free and two were seizure free with some anomalies in
      electroencephalograms. Two patients who had shown no improvement at 6 months had
      decreased seizures at the second follow-up. Our results suggest that monotherapy
      with levetiracetam could be effective and well tolerated in patients with
      childhood absence epilepsy and juvenile absence epilepsy. Prospective, large,
      long-term double-blind studies are needed to confirm these findings.

PMID- 18808425
TI  - Mismatch negativity and frequency representational width in children with
      specific language impairment.
AB  - The aim of this study was to compare the degree of frequency separation that is
      required between tones to generate mismatch negativity (MMN) in a group of
      children with specific language impairment (SLI) and a comparison group, who had
      their temporal processing abilities assessed in a previous experiment. Using a
      1000Hz standard (85%) and 1020, 1050, and 1100Hz deviant tones presented at inter
      stimulus intervals (ISIs) of 200 and 400ms, MMN was compared in 19 children with
      SLI (13 males, six females, age range 7y 4mo-11y 10mo, mean age 9y 7mo [SD 1y
      2mo]), and 19 comparison children (13 males, six females, age range 7y 3mo-11y
      4mo, mean age 9y 5mo [SD 1y 3mo]). Temporal processing ability was assessed by
      the Auditory Fusion Test-Revised. Children with SLI who had poor temporal
      processing abilities generated a positive mismatch response (P-MMR) for 2% tone
      contrasts at 400ms ISI but MMN with larger contrasts. These children also
      generated stronger MMN than the comparison group at 200ms ISI for 2% contrasts.
      Children with SLI who had good temporal processing abilities generated only P-MMR
      in response to contrasts up to 10% for both ISIs. Some children with SLI show an
      inverse relationship between frequency discrimination and temporal processing.
      Furthermore, certain stimulus-related and biological criteria may need to be met
      for P-MMR to switch to MMN.

PMID- 18808426
TI  - Comparison of a coq7 deletion mutant with other respiration-defective mutants in
      fission yeast.
AB  - Among the steps in ubiquinone biosynthesis, that catalyzed by the product of the
      clk-1/coq7 gene has received considerable attention because of its relevance to
      life span in Caenorhabditis elegans. We analyzed the coq7 ortholog (denoted coq7)
      in Schizosaccharomyces pombe, to determine whether coq7 has specific roles that
      differ from those of other coq genes. We first confirmed that coq7 is necessary
      for the penultimate step in ubiquinone biosynthesis, from the observation that
      the deletion mutant accumulated the ubiquinone precursor demethoxyubiquinone-10
      instead of ubiquinone-10. The coq7 mutant displayed phenotypes characteristic of
      other ubiquinone-deficient Sc. pombe mutants, namely, hypersensitivity to
      hydrogen peroxide, a requirement for antioxidants for growth on minimal medium,
      and an elevated production of sulfide. To compare these phenotypes with those of
      other respiration-deficient mutants, we constructed cytochrome c (cyc1) and coq3
      deletion mutants. We also assessed accumulation of oxidative stress in various
      ubiquinone-deficient strains and in the cyc1 mutant by measuring mRNA levels of
      stress-inducible genes and the phosphorylation level of the Spc1 MAP kinase.
      Induction of ctt1, encoding catalase, and apt1, encoding a 25 kDa protein, but
      not that of gpx1, encoding glutathione peroxidase, was indistinguishable in four
      ubiquinone-deficient mutants, indicating that the oxidative stress response
      operates at similar levels in the tested strains. One new phenotype was observed,
      namely, loss of viability in stationary phase (chronological life span) in both
      the ubiquinone-deficient mutant and in the cyc1 mutant. Finally, Coq7 was found
      to localize in mitochondria, consistent with the possibility that ubiquinone
      biosynthesis occurs in mitochondria in yeasts. In summary, our results indicate
      that coq7 is required for ubiquinone biosynthesis and the coq7 mutant is not
      distinguishable from other ubiquinone-deficient mutants, except that its
      phenotypes are more pronounced than those of the cyc1 mutant.

PMID- 18808427
TI  - Dorsal onlay lingual mucosal graft urethroplasty: Comparison of two techniques.
AB  - OBJECTIVES: To compare the results of two different techniques of dorsal onlay
      lingual mucosal graft (LMG) urethroplasty for anterior urethral strictures.
      METHODS: Thirty patients underwent dorsal onlay LMG urethroplasty by Barbagli's
      technique (group I) and 25 through a ventral sagittal urethrotomy approach (group
      II). All of the patients were followed up with a pericatheter urethrography at 3
      weeks, retrograde urethrography with micturating cystourethrography and
      uroflowmetry at 3, 6 and 12 months. RESULTS: Mean follow up was 22 months and 13
      months in group I and II, respectively. The mean peak flow rate increased from
      4.2 mL/s preoperatively to 35.5, 25.06 and 25 mL/s at 3, 6, and 12 months,
      respectively, in group I and from 7.8 mL/s to 34.2, 28.4 and 26.2 mL/s at 3, 6
      and 12 months, respectively, in group II. Five patients in group I and two
      patients in group II had an anastomotic stricture at 12 months. Meatal narrowing
      was seen in five patients in group I and three patients in group II. The overall
      success rate was 83.4% and 76.6% in group I and 90% and 80% in group II at 6 and
      12 months, respectively. One patient had chordee in group I and no patient had
      chordee in group II. There was a shorter operative time and less blood loss in
      group II. CONCLUSIONS: Dorsal onlay LMG urethroplasty through a ventral sagittal
      approach is better than the Barbagli's technique in terms of results and
      complications.

PMID- 18808428
TI  - Modified anatrophic partial nephrectomy with selective renal segmental artery
      clamping to preserve renal function: a preliminary report.
AB  - OBJECTIVES: Partial nephrectomy is effective for preserving renal function, but
      temporary clamping of the renal artery for hemorrhagic control may impair renal
      function due to ischemia/reperfusion injury. Anatrophic partial nephrectomy
      (APNx) has been proposed to minimize renal ischemia/reperfusion injury by
      clamping only the feeding artery. We aimed to evaluate whether anatrophic partial
      nephrectomy (APNx) is useful in preserving renal function and to assess
      variations in renal artery anatomy to determine the feasibility of selective
      segmental artery clamping. METHODS: We performed preoperative renal angiography
      to evaluate the utility of APNx. Perioperative changes in renal function were
      compared between the APNx group and a standard partial nephrectomy group.
      RESULTS: APNx was successful in 18 patients. The mean lengths of the feeding
      artery on preoperative angiography were 20.5 and 6 mm for successful and
      unsuccessful cases, respectively. It was not difficult to clamp the feeding
      artery in 16 patients with lengths >10 mm or with multiple renal arteries.
      Evaluation of renovascular variations on 116 renal angiograms indicated that APNx
      was feasible for 60% and 40% on the right and left sides, respectively. The short
      term increase in the serum creatinine level was significantly smaller after APNx
      than it was after standard partial nephrectomy. CONCLUSIONS: APNx minimizes
      ischemic/reperfusion injury and preserves renal function while achieving
      hemorrhage control. As it can be performed safely in about 50% of cases, it may
      be the option for patients with renal impairment or a solitary kidney.

PMID- 18808429
TI  - Telemedicine in wound care.
AB  - Telemedical wound care is one of the applications of teledermatology. We present
      our experience using telemedicine in the successful assessment and treatment of
      three patients with hard-to-heal ulcers. Three patients were seen at the PEMEX
      General Hospital in Veracruz, Mexico. The first patient was a 53-year-old man
      with hypertension, morbid obesity, chronic venous insufficiency, recurrent
      erysipelas, leg ulcers and lymphoedema. There was one ulcer on his left lower leg
      (20 x 10 cm) and one on his right leg (9 x 7 cm). The second patient was a 73
      year-old woman with class III obesity and ulcers in her right leg, secondary to
      surgical debridement of bullous erysipelas. The third patient was a 51-year-old
      female with rheumatoid arthritis with one ulcer on each leg and chronic
      lymphostasis. Photographs with a digital camera were taken and sent weekly via
      email to a wound care specialist in Mexico City. The photographs allowed the
      expert to diagnose and evaluate the chronic wounds periodically. In the present
      cases, telemedicine allowed us to have a rapid evaluation, diagnosis and
      treatment. The images were of enough quality to be useful and small enough to be
      sent via regular email to the remote physician who immediately gave his feedback.
      The expert was confident to give therapeutic recommendations in this way, and we
      considered this method to be very cost-effective, saving the patient and the
      health care system, especially in transportation.

PMID- 18808430
TI  - Late complication after tropic storm accident: subcutaneous and intracranial
      actinomycetoma.
AB  - We report a 53-year-old farmer who developed subcutaneous and cerebral masses 24
      years after penetrating trauma during a tropic storm. Computed tomography scans,
      magnetic resonance imaging and histopathology disclosed actinomycetoma, a disease
      that rarely develops after trauma and is only occasionally seen with intracranial
      manifestation. Clinically, the cutaneous manifestation resembled acne keloidalis
      nuchae or dissecting folliculitis of the scalp. He was treated by neurosurgery
      and antibiosis.

PMID- 18808431
TI  - Microgravity and the implications for wound healing.
AB  - Wound healing is a sophisticated response ubiquitous to various traumatic stimuli
      leading to an anatomical/functional disruption. The aim of present article was to
      review the current evidence regarding the effects of microgravity on wound
      healing dynamics. Modulation of haemostatic phase because of alteration of
      platelet quantity and function seems probable. Furthermore, production of growth
      factors that are released from activated platelets and infiltration/function of
      inflammatory cells seem to be impaired by microgravity. Proliferation of damaged
      structures is dependent on orchestrated function of various growth factors, for
      example transforming growth factors, platelet-derived growth factor and epidermal
      growth factor, all of which are affected by microgravitational status. Moreover,
      gravity-induced alterations of gap junction, neural inputs, and cell populations
      have been reported. It may be concluded that different cellular and extracellular
      element involved in the healing response are modified through effect of
      microgravity which may lead to impairment in healing dynamics.

PMID- 18808432
TI  - Topical negative pressure wound therapy: a review of its role and guidelines for
      its use in the management of acute wounds.
AB  - Over the past two decades, topical negative pressure (TNP) wound therapy has
      gained wide acceptance as a genuine strategy in the treatment algorithm for a
      wide variety of acute and chronic wounds. Although extensive experimental and
      clinical evidence exists to support its use and despite the recent emergence of
      randomised control trials, its role and indications have yet to be fully
      determined. This article provides a qualitative overview of the published
      literature appertaining to the use of TNP therapy in the management of acute
      wounds by an international panel of experts using standard methods of appraisal.
      Particular focus is applied to the use of TNP for the open abdomen, sternal
      wounds, lower limb trauma, burns and tissue coverage with grafts and dermal
      substitutes. We provide evidence-based recommendations for indications and
      techniques in TNP wound therapy and, where studies are insufficient, consensus on
      best practice.

PMID- 18808433
TI  - Pressure transduction to the thoracic cavity during topical negative pressure
      therapy of a sternotomy wound.
AB  - The present study was performed to examine pressure transduction to the thoracic
      cavity during topical negative pressure (TNP) therapy of a sternotomy wound.
      Seven pigs underwent median sternotomy. Pressure transduction catheters were
      placed on the anterior surface of the heart (under the foam), in the pericardium
      (under the heart), in the left pleura and in the oesophagus at the level of the
      heart. The wound was sealed as for TNP therapy. The vacuum source was set to
      deliver negative pressures between -50 and -200 mmHg. The pressure on the
      anterior surface of the heart changed in a linear relationship with the applied
      negative pressure and was slightly lower than the applied negative pressure (-102
      +/- 9 mmHg at delivered -125 mmHg). Further down in the thoracic cavity, in the
      pericardium (under the heart), in the left pleura and in the oesophagus, the
      wound pressure was only slightly affected by TNP therapy. In conclusion during
      TNP therapy, negative pressure is effectively transmitted to anterior portions of
      the heart. This may explain our recent findings that TNP increases microvascular
      blood flow in the myocardium. The pressure difference between the anterior and
      the posterior portions of the heart causes the right ventricle to be sucked up
      towards the posterior parts of the sternum, where it might be exposed to the
      sharp edges of the sternal bone, which may result in heart injury.

PMID- 18808434
TI  - Wound dressing components degrade proteins detrimental to wound healing.
AB  - Excessive levels of matrix metalloproteinases (MMPs) are present in chronic
      wounds preventing wound closure. Reducing detrimental components may be key in
      healing chronic wounds. Elta Protease-containing wound dressings have been
      observed clinically to resolve inflammation and appear to aid healing in acute
      and chronic recalcitrant wounds. To investigate possible mechanisms of action, in
      vitro tests, zymography, collagenase assays and enzyme-linked immunosorbent
      assays (ELISAs), were performed to evaluate the effect of the dressing proteases
      on detrimental and beneficial wound healing components such as MMPs, Tissue
      Inhibitor of Matrix Metalloproteinases (TIMPs), cytokines and growth factors.
      Standards of pro- and active MMP-2, MMP-9 and chronic wound fluid (CWF) were
      prepared. Degradation of target proteins was enhanced by increased Elta Protease
      concentration, temperature and incubation time. Incubation with serial dilutions
      of the Elta Proteases resulted in nearly complete degradation of all MMP
      standards. After a 30-minute incubation, twofold diluted Elta Proteases degraded
      >90% of the gelatinases in CWF. ELISAs showed that Elta Proteases effectively
      degraded MMP-9 and tumour necrosis factor (TNF-alpha). In contrast, Platelet
      Derived Growth Factor (PDGF) and interleukin 1 beta were resistant to degradation
      by Elta Proteases. These results suggest that Elta Protease dressings appear to
      deactivate detrimental components in CWF, which may reduce wound bed contact with
      harmful proteins.

PMID- 18808435
TI  - Estimating fitness consequences of dispersal: a road to 'know-where'? Non-random
      dispersal and the underestimation of dispersers' fitness.
AB  - 1. Many studies investigating fitness correlates of dispersal in vertebrates
      report dispersers to have lower fitness than philopatric individuals. However, if
      dispersers are more likely to produce dispersing young or are more likely to
      disperse again in the next year(s) than philopatric individuals, there is a risk
      that fitness estimates based on local adult survival and local recruitment will
      be underestimated for dispersers. 2. We review the available empirical evidence
      on parent-offspring resemblance and individual lifelong consistency in dispersal
      behaviour, and relate these studies to recent studies of fitness correlates of
      dispersal in vertebrates. 3. Of the 12 studies testing directly for parent
      offspring resemblance in dispersal propensity, five report a significant
      resemblance. The average effect size (r) of parent-offspring resemblance in
      dispersal was 0.15 [95% confidence interval (CI) = 0.07-0.22], with no difference
      between the sexes (average weighted effect size of 0.12 (0.08-0.16) and 0.16
      (0.11-0.20) for females and males, respectively). Only three studies report data
      on within-individual consistency in dispersal propensity, of which two suggest
      dispersers to be more likely to disperse again. 4. To assess the magnitude of
      fitness underestimation expected for dispersing individuals depending on the
      heritability of dispersal distance and study area size, we used a simulation
      approach. Even when study area size is 10 times the mean dispersal distance,
      local recruitment per breeding event may be underestimated by 4-10%, generating a
      potential difference of 4-60% in average lifetime production of recruits between
      dispersing and philopatric individuals, with larger differences in long-lived
      species. 5. Estimates of both fitness correlates of dispersal and parent
      offspring resemblance or within-individual consistency in dispersal behaviour
      have been reported for 11 species. Although some comparisons suggest genuine
      differences in fitness components between philopatric and dispersing individuals,
      others, based on adult and juvenile survival, are open to the alternative
      explanation of biased fitness estimates. 6. We list three potential ways of
      reducing the risk of making wrong inferences on biased fitness estimates due to
      such non-random dispersal behaviour between dispersing and philopatric
      individuals: (a) diagnosing effects of non-random dispersal, (b) reducing the
      effects of spatially limited study area and (c) performing controlled
      experiments.

PMID- 18808436
TI  - Spatial distribution of limited resources and local density regulation in
      juvenile Atlantic salmon.
AB  - 1. Spatial heterogeneity of resources may influence competition among individuals
      and thus have a fundamental role in shaping population dynamics and carrying
      capacity. In the present study, we identify shelter opportunities as a limiting
      resource for juvenile Atlantic salmon (Salmo salar L.). Experimental and field
      studies are combined in order to demonstrate how the spatial distribution of
      shelters may influence population dynamics on both within and among population
      scales. 2. In closed experimental streams, fish performance scaled negatively
      with decreasing shelter availability and increasing densities. In contrast, the
      fish in open stream channels dispersed according to shelter availability and
      performance of fish remaining in the streams did not depend on initial density or
      shelters. 3. The field study confirmed that spatial variation in densities of 1
      year-old juveniles was governed both by initial recruit density and shelter
      availability. Strength of density-dependent population regulation, measured as
      carrying capacity, increased with decreasing number of shelters. 4. Nine rivers
      were surveyed for spatial variation in shelter availability and increased shelter
      heterogeneity tended to decrease maximum observed population size (measured using
      catch statistics of adult salmon as a proxy). 5. Our studies highlight the
      importance of small-scale within-population spatial structure in population
      dynamics and demonstrate that not only the absolute amount of limiting resources
      but also their spatial arrangement can be an important factor influencing
      population carrying capacity.

PMID- 18808437
TI  - Is there a possible link between chronic trauma of the palate induced by a
      maxillary denture and the appearance of melanoma? Discussion of two case reports
      and a review of the literature.

PMID- 18808438
TI  - Treatment of lipoid proteinosis  with acitretin: a case report.

PMID- 18808439
TI  - Why do Californian striders fly?
AB  - Discerning the adaptive significance of migratory strategies poses significant
      challenges, not the least of which is measuring migratory capability in natural
      populations. We take advantage of a visible migratory dimorphism to study
      variation in migratory capability in the stream-dwelling water strider, Aquarius
      remigis. Theory predicts loss of migratory capability in this species because
      streams have been viewed as stable and persistent habitats. As expected, A.
      remigis lack wings throughout most of North America. However, Californian
      populations are noted for unexpectedly high frequencies of winged, migratory
      morphs. To deduce the adaptive significance of this anomalous regional variation,
      we compare proportion winged among 37 Californian populations. We discover a
      strong, positive correlation with altitude, but no correlations with latitude,
      rainfall or stream size. A common garden experiment reveals that both proportion
      winged and its reaction norm to temperature differ genetically among populations,
      and a half-sibling experiment demonstrates that wing morph has high heritability,
      moderate genetic correlations across environments and a significant genotype by
      environment interaction. These results support the hypothesis that proportion
      winged and its reaction norm to temperature have diverged genetically in
      California. We conclude that high migratory capability is an evolutionary
      adaptation to the unusual harshness and instability of Californian stream
      habitats, and particularly to the high elevational gradients and extreme seasonal
      variation characteristic of montane streams.

PMID- 18808440
TI  - Cranial shape and correlated characters in crocodilian evolution.
AB  - Crocodilians show a high degree of cranial variation and convergence throughout
      their 80 million-year fossil record that complicates their phylogenetic
      reconstruction. Conflicting phylogenetic results from different data partitions
      and character homoplasies typify crocodilian phylogeny, and differences between
      molecular and morphological phylogenetic hypotheses are believed to be associated
      with the slender-snout skull shape of Gavialis gangeticus and Tomistoma
      schlegelii. Slender-snout skulls are one of five identified eusuchian cranial
      ecomorph shape categories (ESCs) thought to reflect functional or ecological
      specialization. This paper tested the effect of transitions among general, blunt
      and slender ESCs on cranial character-state distributions in phylogeny using the
      concentrated changes test. In addition, 'tree-free' character compatibility
      analysis of character independence was conducted on the morphological character
      matrix to determine if character correlations are observed independent of
      specific tree topologies. Results suggest cranial ESCs do affect cranial
      character-state gains in phylogeny. Concentrated changes identify a broad suite
      of character-state changes that significantly correlate with transitions to
      slender, general and blunt ESCs on morphological, molecular and combined-data
      tree topologies, but numbers of correlated characters for each category differ
      according to topology. Character compatibility analysis results do not mirror the
      concentrated changes test results and reflect hierarchically distributed support
      throughout the data. As cranial ESCs affect character-state transitions, it is
      possible that nonphylogenetic variables could affect inferences of crocodilian
      phylogeny by affecting cranial morphology.

PMID- 18808441
TI  - Placental invasiveness and brain-body allometry in eutherian mammals.
AB  - Brain growth is a key trait in the evolution of mammalian life history. Brain
      development should be mediated by placentation, which determines patterns of
      resource transfer from mothers to fetal offspring. Eutherian placentation varies
      in the extent to which a maternal barrier separates fetal tissues from maternal
      blood. We demonstrate here that more invasive forms of placentation are
      associated with substantially steeper brain-body allometry, faster prenatal brain
      growth and slower prenatal body growth. On the basis of the physiological
      literature we suggest a simple mechanism for these differences: in species with
      invasive placentation, where the placenta is bathed directly in maternal blood,
      fatty acids essential for brain development can be readily extracted by the
      fetus, but in species with less invasive placentation they must be synthesized by
      the fetus. Hence, with regard to brain-body allometry and prenatal growth
      patterns, eutherian mammals are structured into distinct groups differing in
      placental invasiveness.

PMID- 18808442
TI  - The expression patterns of Pax7 in satellite cells during overload-induced rat
      adult skeletal muscle hypertrophy.
AB  - AIM: Activated satellite cells (SCs) have the ability to reacquire a quiescent,
      undifferentiated state. Pax7 plays a crucial role in allowing activated SCs to
      undergo self-renewal. Because the increase in the SC population is induced during
      overload-induced skeletal muscle hypertrophy, it is possible that Pax7-regulated
      SC self-renewal is involved in the modulation of the SC population during the
      functional overload of skeletal muscles. However, the characteristics of the
      expression patterns of Pax7 in SCs during the functional overload of adult
      skeletal muscles are poorly understood. METHODS: Using immunohistochemical
      approaches, we examined the temporal and spatial expression patterns of Pax7
      expressed in SCs during the functional overloading of rat skeletal muscles.
      RESULTS: The time course of Pax7 expression in SCs was similar to that of the
      expression of the differentiation regulatory factor myogenin during the early
      stage of functional overload. However, the percentage of SCs that expressed Pax7
      was markedly higher than that of the SCs that expressed myogenin. Coexpression of
      Pax7 and myogenin was not detected in SCs. In addition, the expression of cyclin
      dependent kinase inhibitor p21, which regulates cell cycle arrest and
      differentiation, was not detected in Pax7-positive SCs. CONCLUSION: These results
      suggest that Pax7-regulated self-renewal of SCs may be induced during the early
      stage of functional overload and may contribute to modulating the SC population
      in hypertrophied muscles. Furthermore, it was suggested that the numbers of SCs
      which underwent self-renewal may be higher than that of SCs which were provided
      as the additional myonuclei for hypertrophying myofibres.

PMID- 18808443
TI  - Review article: pharmacological therapy for hepatocellular carcinoma with
      sorafenib and other oral agents.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is the fifth most common malignancy
      worldwide. Unresectable disease patients have median survival of few months.
      There is a substantial need for novel treatments for patients with advanced HCC.
      AIM: To provide an update review of mechanism of hepatocarcinigenesis and
      systemic therapies for HCC and the relevant role of Sorafenib in patients with
      advanced disease. METHODS: A Medline search was performed to identify pertinent
      original research and review articles. Selected references in these articles were
      also evaluated. RESULTS: Systemic chemotherapy for HCC has been quite
      ineffective. Preclinical studies demonstrated that Raf/MAPK-ERK kinase
      (MEK)/Extracellular signal regulated kinase (ERK) pathway has a role in HCC. HCC
      tumours are highly vascularized and vascular endothelial growth factor (VEGF)
      augments HCC development and metastasis. Sorafenib blocks tumour cell
      proliferation by targeting Raf/MEK/ERK signalling and exerts an antiangiogenic
      effect by targeting VEGF receptors-2/3 and platelet derived growth factor
      receptor beta tyrosine kinases. CONCLUSIONS: Currently available therapies are
      not effective for patients with advanced HCC. Sorafenib has demonstrated for the
      first time to prolong survival in patients with advanced HCC, and it is the new
      reference standard for systemic treatment in these patients.

PMID- 18808444
TI  - The cost-utility of high dose oral mesalazine for moderately active ulcerative
      colitis.
AB  - BACKGROUND: Mesalazine (mesalamine) is standard first line treatment for
      moderately active ulcerative colitis (UC). Recently, doubling the mesalazine dose
      (Asacol 4.8 g/day) was shown to improve efficacy with no increase in adverse
      events. The cost-effectiveness of this strategy remains unknown. AIM: To assess
      the cost-utility of high dose (HD) mesalazine (Asacol 4.8 g/day) compared with
      standard dose (SD) mesalazine (Asacol 2.4 g/day) as first line treatment for
      moderately active UC. METHODS: The costs and benefits associated with a treatment
      pathway beginning with HD or SD mesalazine were determined over 12 weeks using a
      decision tree analytical model. RESULTS: A 12-week treatment pathway starting
      with HD mesalazine cost an average of 2382 pounds per patient compared with 2474
      pounds for SD mesalazine and generated 0.0016 more quality adjusted life years
      (QALYs). HD mesalazine dominated SD mesalazine, being both more effective and
      less costly. HD mesalazine treatment resulted in fewer patients requiring surgery
      or hospitalization for intensive pharmacological treatment. Probabilistic
      sensitivity analysis indicated a 72% chance that HD mesalazine was cost
      effective, based on a cost/QALY threshold of 30,000 pounds. CONCLUSIONS: This
      study suggests that HD mesalazine represents a cost-effective alternative to SD
      mesalazine for moderately active UC, while potentially reducing the need for
      hospitalization.

PMID- 18808445
TI  - The effect of naloxone-3-glucuronide on colonic transit time in healthy men after
      acute morphine administration: a placebo-controlled double-blinded crossover
      preclinical volunteer study.
AB  - BACKGROUND: Constipation is a significant side effect of opioid therapy. We have
      previously demonstrated that naloxone-3-glucuronide (NX3G) antagonizes the
      motility-lowering-effect of morphine in the rat colon. AIM: To find out whether
      oral NX3G is able to reduce the morphine-induced delay in colonic transit time
      (CTT) without being absorbed and influencing the analgesic effect. METHODS:
      Fifteen male volunteers were included. Pharmacokinetics: after oral
      administration of 0.16 mg/kg NX3G, blood samples were collected over a 6-h
      period. Pharmacodynamics: NX3G or placebo was then given at the start time and
      every 4 h thereafter. Morphine (0.05 mg/kg) or placebo was injected s.c. 2 h
      after starting and thereafter every 6 h for 24 h. CTT was measured over a 48-h
      period by scintigraphy. Pressure pain threshold tests were performed. RESULTS:
      Neither NX3G nor naloxone was detected in the venous blood. The slowest transit
      time was observed during the morphine phase, which was significantly different
      from morphine with NX3G and placebo. The pain perception was not significantly
      influenced by NX3G. CONCLUSIONS: Orally administered NX3G is able to reverse the
      morphine-induced delay of CTT in humans without being detected in peripheral
      blood samples. Therefore, NX3G may improve symptoms of constipation in-patients
      using opioid medication without affecting opioid-analgesic effects.

PMID- 18808446
TI  - The effect of mesalazine therapy on quality of life in patients with mildly and
      moderately active ulcerative colitis.
AB  - BACKGROUND: Ulcerative colitis (UC) has a major impact on the quality of life
      (QoL) of affected patients. Patient-reported outcomes have not been thoroughly
      evaluated in patients with UC receiving oral mesalazine (mesalamine). AIM: To
      examine the effect of mesalazine on QoL of patients with mildly and moderately
      active UC and assess the time course of change, baseline disease severity,
      mesalazine dose and responder status on QoL parameters. METHODS: Inflammatory
      Bowel Disease Questionnaire (IBDQ) data were combined from two double-blind,
      randomized, multicentre, active-controlled trials assessing 2.4 and 4.8 g/day
      oral delayed-release mesalazine in 687 patients. Mean score changes from baseline
      were compared at 3 and 6 weeks and effects of baseline severity, mesalazine dose
      and response to therapy were examined. RESULTS: Mesalazine significantly improved
      IBDQ scores at 3 and 6 weeks (mean increase, 29.6 and 39.7 points, respectively;
      P < 0.0001 for both). Improvement was greater for patients with moderate disease.
      Greater week 6 changes occurred in clinical responders than nonresponders (50.1
      vs. 23.6 points, respectively; P < 0.0001). CONCLUSIONS: Delayed-release oral
      mesalazine produces significant clinical and statistical improvements in QoL of
      patients with UC by 3 weeks, with further improvement at 6 weeks.

PMID- 18808447
TI  - Mechanisms of Zn2+ efflux in cultured cortical neurons.
AB  - Zinc dyshomeostasis in brain might be involved in the pathogenesis of brain
      diseases such as Alzheimer's disease and stroke. Resting neurons tightly regulate
      and maintain low to subnanomolar levels of intracellular free Zn2+, but
      mechanisms of normal Zn2+ homeostasis are poorly understood. In this study, the
      mechanisms of transporter-mediated Zn2+extrusion across the plasma membrane of
      cultured cortical neurons were studied. Changes in intracellular free Zn2+ levels
      were tracked in individual neurons by microfluorometry using a Zn2+ selective
      fluorophore, FluoZin3. Unopposed Zn2+efflux was measured by first loading
      cultured cortical neurons with Zn2+ then reducing extracellular Zn2+ to near zero
      by addition of EDTA. Studies revealed that the primary means of Zn2+ efflux in
      cortical neurons required both extracellular Na+ and Ca2+. The actions of either
      Na+ or Ca2+ on Zn2+ efflux were blunted in the absence of the other cation.
      Reversed Na+ gradients could induce Zn2+ uptake. The Na+ dependence of Zn2+
      efflux was not affected by a small pHo shift (7.6-8);whereas an effect of Ca2+
      was not observed at pHo 8. In summary, a Na+, Ca2+/Zn2+ exchanger mechanism is
      proposed to be the primary transport mechanism that extrudes Zn2+ when neuronal
      intracellular free Zn2+ levels rise.

PMID- 18808448
TI  - Expression of mutant SOD1 in astrocytes induces functional deficits in motoneuron
      mitochondria.
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder
      characterized by motoneuron degeneration resulting in paralysis and eventual
      death. ALS is regarded as a motoneuron-specific disorder but increasing evidence
      indicates non-neuronal cells play a significant role in disease pathogenesis.
      Although the precise aetiology of ALS remains unclear, mutations in the
      superoxide dismutase (SOD1) gene are known to account for approximately 20% of
      familial ALS. We examined the influence of SOD1(G93A) expression in astrocytes on
      mitochondrial homeostasis in motoneurons in a primary astrocyte : motoneuron co
      culture model. SOD1(G93A) expression in astrocytes induced changes in
      mitochondrial function of both SOD1(G93A) and wild-type motoneurons. In the
      presence of SOD1(G93A) astrocytes, mitochondrial redox state of both wild-type
      and SOD1(G93A) motoneurons was more reduced and mitochondrial membrane potential
      decreased. While intra-mitochondrial calcium levels [Ca(2+)](m) were elevated in
      SOD1(G93A) motoneurons, changes in mitochondrial function did not correlate with
      [Ca(2+)](m). Thus, expression of SOD1(G93A) in astrocytes directly alters
      mitochondrial function even in embryonic motoneurons, irrespective of genotype.
      These early deficits in mitochondrial function induced by surrounding astrocytes
      may increase the vulnerability of motoneurons to other neurotoxic mechanisms
      involved in ALS pathogenesis.

PMID- 18808449
TI  - Human ProNGF: biological effects and binding profiles at TrkA, P75NTR and
      sortilin.
AB  - Nerve growth factor (NGF) promotes cell survival via binding to the tyrosine
      kinase receptor A (TrkA). Its precursor, proNGF, binds to p75(NTR) and sortilin
      receptors to initiate apoptosis. Current disagreement exists over whether proNGF
      acts neurotrophically following binding to TrkA. As in Alzheimer's disease the
      levels of proNGF increase and TrkA decrease, it is important to clarify the
      properties of proNGF. Here, wild-type and cleavage-resistant mutated forms (M) of
      proNGF were engineered and their binding characteristics determined. M-proNGF and
      NGF bound to p75(NTR) with similar affinities, whilst M-proNGF had a lower
      affinity than NGF for TrkA. M-proNGF behaved neurotrophically, albeit less
      effectively than NGF. M-proNGF addition resulted in phosphorylation of TrkA and
      ERK1/2, and in PC12 cells elicited neurite outgrowth and supported cell survival.
      Conversely, M-proNGF addition to cultured cortical neurons initiated caspase 3
      cleavage. Importantly, these biological effects were shown to be mediated by
      unprocessed M-proNGF. Surprisingly, binding of the pro region alone to TrkA, at a
      site other than that of NGF, caused TrkA and ERK1/2 phosphorylation. Our data
      show that M-proNGF stimulates TrkA to a lesser degree than NGF, suggesting that
      in Alzheimer brain the increased proNGF : NGF and p75(NTR) : TrkA ratios may
      permit apoptotic effects to predominate over neurotrophic effects.

PMID- 18808451
TI  - Extracellular matrix protein SC1/hevin in the hippocampus following pilocarpine
      induced status epilepticus.
AB  - Pilocarpine-induced status epilepticus (SE) mimics many features of temporal lobe
      epilepsy and is a useful model to study neural changes that result from prolonged
      seizure activity. In this study, distribution of the anti-adhesive extracellular
      matrix protein SC1 was examined in the rat hippocampus following SE. Western
      blotting showed decreased levels of SC1 protein in the week following SE.
      Immunohistochemistry demonstrated that the decrease in overall SC1 protein levels
      was reflected by a reduction of SC1 signal in granule cells of the dentate gyrus.
      Interestingly, levels of SC1 protein in neurons of the seizure-resistant CA2
      sector of the hippocampus did not change throughout the seizure time course.
      However, at 1 day post-SE, a subset of neurons of the hippocampal CA1, CA3, and
      hilar regions, which are noted for extensive neuronal degeneration after SE,
      exhibited a transient increase in SC1 signal. Neurons exhibiting enhanced SC1
      signal were not detected at 7 days post-SE. The cellular stress response was also
      examined. A prominent induction of heat-shock protein (Hsp70) and Hsp27 was
      detected following SE, while levels of constitutively expressed Hsp40, Hsp90,
      Hsp110, and Hsc70 showed little change at the time points examined. The subset of
      neurons that demonstrated a transient increase in SC1 colocalized with the
      cellular stress marker Hsp70, the degeneration marker Fluoro-Jade B, and the
      neuron activity marker activity-regulated cytoskeleton-associated protein (Arc).
      Taken together, these findings suggest that SC1 may be a component of the 'matrix
      response' involved in remodeling events associated with neuronal degeneration
      following neural injury.

PMID- 18808450
TI  - Caffeine protects against MPTP-induced blood-brain barrier dysfunction in mouse
      striatum.
AB  - The blood-brain barrier (BBB) is important physiologically. Pathologically, BBB
      disruption has been implicated in a wide spectrum of neurological disorders
      including Parkinson's disease (PD). Recent studies indicate that caffeine is
      protective against PD, but by poorly understood mechanisms. Using a MPTP
      neurotoxin model of PD we tested the hypothesis that the protective actions of
      caffeine were because of, at least in part, preventing MPTP-induced BBB
      dysfunction. FVB mice were pre-treated with caffeine (10 mg/kg, i.p.) or saline
      for 7 days prior to initiation of neurotoxin treatments; during the 7 days of
      neurotoxin treatment, caffeine or saline continued to be administered 10 min
      before each dose of MPTP (20 mg/kg, i.p.). Striatum (and for some studies
      hippocampus and cerebral cortex as well) were evaluated for BBB leakage, tight
      junction protein expression levels, integrity of dopaminergic neurons, and
      activation of astrocytes and microglia using immunostaining, immunoblotting and
      real-time PCR techniques. We found that caffeine blocked MPTP-induced decreases
      in numbers of tyrosine hydroxylase-positive dopaminergic neurons, increases in
      leakage of Evan's blue dye and FITC-albumin in striatum but not in cerebral
      cortex or hippocampus, decreases in levels of the tight junction proteins
      occludin and ZO-1, and increases in reactive gliosis. Our results suggest that
      caffeine might protect against PD and PD-like features in animal models, in part,
      by stabilizing the BBB.

PMID- 18808453
TI  - Refunctionalization of the ancient rice blast disease resistance gene Pit by the
      recruitment of a retrotransposon as a promoter.
AB  - The plant genome contains a large number of disease resistance (R) genes that
      have evolved through diverse mechanisms. Here, we report that a long terminal
      repeat (LTR) retrotransposon contributed to the evolution of the rice blast
      resistance gene Pit. Pit confers race-specific resistance against the fungal
      pathogen Magnaporthe grisea, and is a member of the nucleotide-binding site
      leucine-rich repeat (NBS-LRR) family of R genes. Compared with the non-functional
      allele Pit(Npb), the functional allele Pit(K59) contains four amino acid
      substitutions, and has the LTR retrotransposon Renovator inserted upstream.
      Pathogenesis assays using chimeric constructs carrying the various regions of
      Pit(K59) and Pit(Npb) suggest that amino acid substitutions might have a
      potential effect in Pit resistance; more importantly, the upregulated promoter
      activity conferred by the Renovator sequence is essential for Pit function. Our
      data suggest that transposon-mediated transcriptional activation may play an
      important role in the refunctionalization of additional 'sleeping' R genes in the
      plant genome.

PMID- 18808452
TI  - Impairment of nigrostriatal dopamine neurotransmission by manganese is mediated
      by pre-synaptic mechanism(s): implications to manganese-induced parkinsonism.
AB  - The long-term consequences of chronic manganese (Mn) exposure on neurological
      health is a topic of great concern to occupationally-exposed workers and in
      populations exposed to moderate levels of Mn. We have performed a comprehensive
      assessment of Mn effects on dopamine (DA) synapse markers using positron emission
      tomography (PET) in the non-human primate brain. Young male Cynomolgus macaques
      were given weekly i.v. injections of 3.3-5.0 mg Mn/kg (n = 4), 5.0-6.7 mg Mn/kg
      (n = 5), or 8.3-10.0 mg Mn/kg (n = 3) for 7-59 weeks and received PET studies of
      various DA synapse markers before (baseline) and at one or two time points during
      the course of Mn exposure. We report that amphetamine-induced DA release measured
      by PET is markedly impaired in the striatum of Mn-exposed animals. The effect of
      Mn on DA release was present in the absence of changes in markers of dopamine
      terminal integrity determined in post-mortem brain tissue from the same animals.
      These findings provide compelling evidence that the effects of Mn on DA synapses
      in the striatum are mediated by inhibition of DA neurotransmission and are
      responsible for the motor deficits documented in these animals.

PMID- 18808454
TI  - The BTB ubiquitin ligases ETO1, EOL1 and EOL2 act collectively to regulate
      ethylene biosynthesis in Arabidopsis by controlling type-2 ACC synthase levels.
AB  - Ethylene biosynthesis is directed by a family of 1-aminocyclopropane-1-carboxylic
      acid (ACC) synthases (ACS) that convert S-adenosyl-l-methionine to the immediate
      precursor ACC. Members of the type-2 ACS subfamily are strongly regulated by
      proteolysis with various signals stabilizing the proteins to increase ethylene
      production. In Arabidopsis, this turnover is mediated by the ubiquitin/26 S
      proteasome system, using a broad complex/tramtrack/bric-a-brac (BTB) E3 assembled
      with the ETHYLENE OVERPRODUCER 1 (ETO1) BTB protein for target recognition. Here,
      we show that two Arabidopsis BTB proteins closely related to ETO1, designated
      ETO1-like (EOL1) and EOL2, also negatively regulate ethylene synthesis via their
      ability to target ACSs for breakdown. Like ETO1, EOL1 interacts with type-2 ACSs
      (ACS4, ACS5 and ACS9), but not with type-1 or type-3 ACSs, or with type-2 ACS
      mutants that stabilize the corresponding proteins in planta. Whereas single and
      double mutants affecting EOL1 and EOL2 do not show an ethylene-related phenotype,
      they exaggerate the effects caused by inactivation of ETO1, and further increase
      ethylene production and the accumulation of ACS5 in eto1 plants. The triple eto1
      eol1 eol2 mutant phenotype can be effectively rescued by the ACS inhibitor
      aminoethoxyvinylglycine, and by silver, which antagonizes ethylene perception.
      Together with hypocotyl growth assays showing that the sensitivity and response
      kinetics to ethylene are normal, it appears that ethylene synthesis, but not
      signaling, is compromised in the triple mutant. Collectively, the data indicate
      that the Arabidopsis BTB E3s assembled with ETO1, EOL1 and EOL2 work together to
      negatively regulate ethylene synthesis by directing the degradation of type-2 ACS
      proteins.

PMID- 18808455
TI  - Type-B monogalactosyldiacylglycerol synthases are involved in phosphate
      starvation-induced lipid remodeling, and are crucial for low-phosphate
      adaptation.
AB  - Mono- and digalactosyldiacylglycerol (MGDG and DGDG, respectively) constitute the
      bulk of membrane lipids in plant chloroplasts. Mutant analyses in Arabidopsis
      have shown that these galactolipids are essential for chloroplast biogenesis and
      photoautotrophic growth. Moreover, these non-phosphorous lipids are proposed to
      participate in low-phosphate (Pi) adaptations. Under Pi-limited conditions, a
      drastic accumulation of DGDG occurs concomitantly with a large reduction in
      membrane phospholipids, suggesting that plants substitute DGDG for phospholipids
      during Pi starvation. Previously, we reported that among the three MGDG synthase
      genes (MGD1, MGD2 and MGD3), the type-B MGD2 and MGD3 are upregulated in parallel
      with DGDG synthase genes during Pi starvation. Here, we describe the
      identification and characterization of T-DNA insertional mutants of Arabidopsis
      type-B MGD genes. Under Pi-starved conditions, the mgd3-1 mutant showed a drastic
      reduction in DGDG accumulation, particularly in the root, indicating that MGD3 is
      the main isoform responsible for DGDG biosynthesis in Pi-starved roots. Moreover,
      in the roots of mgd2 mgd3 plants, Pi stress-induced accumulation of DGDG was
      almost fully abolished, showing that type-B MGD enzymes are essential for
      membrane lipid remodeling in Pi-starved roots. Reductions in fresh weight, root
      growth and photosynthetic performance were also observed in these mutants under
      Pi-starved conditions. These results demonstrate that Pi stress-induced membrane
      lipid remodeling is important in plant growth during Pi starvation. The
      widespread distribution of type-B MGD genes in land plants suggests that membrane
      lipid remodeling mediated by type-B MGD enzymes is a potent adaptation to Pi
      deficiency for land plants.

PMID- 18808456
TI  - An N-terminal diacidic motif is required for the trafficking of maize aquaporins
      ZmPIP2;4 and ZmPIP2;5 to the plasma membrane.
AB  - Maize plasma membrane aquaporins (ZmPIPs, where PIP is the plasma membrane
      intrinsic protein) fall into two groups, ZmPIP1s and ZmPIP2s, which, when
      expressed alone in mesophyll protoplasts, are found in different subcellular
      locations. Whereas ZmPIP1s are retained in the endoplasmic reticulum (ER),
      ZmPIP2s are found in the plasma membrane (PM). We previously showed that, when co
      expressed with ZmPIP2s, ZmPIP1s are relocalized to the PM, and that this
      relocalization results from the formation of hetero-oligomers between ZmPIP1s and
      ZmPIP2s. To determine the domains responsible for the ER retention and PM
      localization, respectively, of ZmPIP1s and ZmPIP2s, truncated and mutated ZmPIPs
      were generated, together with chimeric proteins created by swapping the N- or C
      terminal regions of ZmPIP2s and ZmPIP1s. These mutated proteins were fused to the
      mYFP and/or mCFP, and the fusion proteins were expressed in maize mesophyll
      protoplasts, and were then localized by microscopy. This allowed us to identify a
      diacidic motif, DIE (Asp-Ile-Glu), at position 4-6 of the N-terminus of ZmPIP2;5,
      that is essential for ER export. This motif was conserved and functional in
      ZmPIP2;4, but was absent in ZmPIP2;1. In addition, we showed that the N-terminus
      of ZmPIP2;5 was not sufficient to cause the export of ZmPIP1;2 from the ER. A
      study of ZmPIP1;2 mutants suggested that the N- and C-termini of this protein are
      probably not involved in ER retention. Together, these results show that the
      trafficking of maize PM aquaporins is differentially regulated depending on the
      isoform, and involves a specific signal and mechanism.

PMID- 18808457
TI  - Policy analysis and policy implementation: can nursing manage without them?

PMID- 18808458
TI  - University of life or academia? A review of community matrons/case managers
      continuing professional development; accessing a post-graduate programme without
      meeting the current academic entry criteria.
AB  - AIMS: To inform managers and gatekeepers of the pre-requisites for staff engaging
      in post-graduate level study. To acknowledge the support students in new roles
      require in clinical practice and continuing professional development (CPD).
      BACKGROUND: A post-graduate course for case managers/community matrons was
      developed as a rapid response to government policy. As a result, candidates
      entered this programme with non-traditional requirements. However, this did not
      appear to hinder their success. EVALUATION: Student entry data and their
      achievements on completion were collected and compared with another post-graduate
      course that did require standard entry academic requirements. Final results were
      analysed and a narrative obtained from students and mentors. KEY ISSUES:
      Gatekeepers should recognize the importance of past experience and motivation of
      candidates in relation to CPD and also the student's insight and self-awareness
      when accessing courses. CONCLUSION: Candidates accessing post-graduate courses
      can achieve learning outcomes at an advanced level when given the right support
      and are capable of undertaking the role of case manager/community matron .
      IMPLICATIONS FOR NURSING MANAGEMENT: The article is relevant in light of the
      current financial constraints for Trusts to ration the funding of CPD. Choosing
      the right person to attend the right course often depends on the manager's
      discretion and not necessarily the candidates' ability or motivation. It
      highlights the importance of not only recognizing the candidates' academic level
      but also their motivation to study, and with careful selection candidates should
      be allowed the opportunity to access higher levels of CPD. Fitness to practice is
      also an important aspect to consider on completion of a course and this can be
      achieved with the mapping of competencies in relation to the post holder's
      specific job.

PMID- 18808459
TI  - Teamwork in primary care mental health: a policy analysis.
AB  - AIM: This paper reports a policy analysis conducted to examine the potential
      impact of recent mental health policy on team working in Primary Care Mental
      Health in England. METHOD: An analysis of relevant policy documents was
      conducted. From an original selection of 49 documents, 15, which had significant
      implications for Primary Care Mental Health Teams, were analysed thematically.
      FINDINGS: There were no clear guidelines or objectives for Primary Care Mental
      Health Teams evident from the policy analysis. Collaborative working was
      advocated, yet other elements in the policies were likely to prevent this
      occurring. There was a lack of clarity concerning the role and function of new
      professions within Primary Care Mental Health Teams, adding further uncertainty
      to an already confused situation. CONCLUSION: This uncertainty has the potential
      to reinforce professional barriers and increase the current difficulties with
      team working. IMPLICATIONS TO NURSING MANAGERS: An analysis of recent policy
      contributes to our understanding of the context of care. The lack of clarity in
      current health policy presents a significant challenge for those managing primary
      care mental health teams. Team working is likely to improve if targets, processes
      and responsibilities are made clearer.

PMID- 18808460
TI  - Four parts or one whole: The National Health Service (NHS) post-devolution.
AB  - AIM(S): There is a need for nurse and midwifery managers to have an understanding
      of devolution and its implications for them and their colleagues. This paper will
      explain devolution, consider some health and social care policy including
      similarities and differences, and assess the impact of devolution on the nursing
      workforce and the regulation of nursing across the four countries of the United
      Kingdom (UK). BACKGROUND: If managers are to manage effectively it is critical
      that they remain aware of emerging policy development and outcomes across the UK.
      It is now more important than ever that nurses maintain a keen eye on the impact
      divergent policy is having on practice as well as the UK nursing workforce.
      EVALUATION: The impact of devolution across the UK will be explored using
      convergence and divergence as a framework; commencing by providing an overview of
      devolution and health, moving on to examine health policy in action across the
      four countries. KEY ISSUES: Healthcare is highly political in nature. Devolution
      has implications for all, and adds to the complexity of health and social care
      provision. If managers are to manage effectively it is critical that they remain
      aware of emerging policy development and outcomes across the UK. CONCLUSION: It
      is equally important that nurses, and nurse managers, develop and draw upon their
      political leadership skills, actively engaging in policy debates to ensure that
      when policies are translated into practice their outcomes are optimal in terms of
      quality, efficiency and sustainability. Implications for nursing management There
      is a need for nurse and midwifery managers to have an understanding of post
      devolution structures and how they operate in order to work effectively, as well
      as to learn from the experiences of other parts of the UK.

PMID- 18808461
TI  - Service user involvement in the NHS in England: genuine user participation or a
      dogma-driven folly?
AB  - AIM: This paper will catalogue and debate the recent policies that seek to extend
      the role of health Service Users in England. For operational purposes, the term
      'Service User' refers collectively to individual patients and also to the public
      at large. BACKGROUND: The provision of principal features of user involvement are
      twofold. First, it concerns more personalized services to individuals. Second, it
      represents recognition that the 60 million potential users of health services
      have a rightful role in determining the design of service development and
      delivery. KEY ISSUES: The paper will review the conceptual and ideological basis
      for current policy in relation to users. For a while, involvement policies began
      as benign benevolence, users now find themselves as the means to distributing
      resources in a way that was originally unintended. CONCLUSIONS: The dilemmas
      raised by these policies for both users and providers will be explored and
      analysed. IMPLICATION FOR NURSING MANAGEMENT: The challenge for managers resides
      in the empirical evidence. This indicates despite undoubted improvements in the
      service as a whole, data suggests that at the operational level, care is still
      far from user centred. The task for policy makers and managers as far as user
      involvement is concerned, is to move from aspiration to reality.

PMID- 18808462
TI  - Achieving evidence-based nursing practice: impact of the Caledonian Development
      Model.
AB  - AIM: To determine the impact of the Caledonian Development Model, designed to
      promote evidence-based practice. BACKGROUND: The model features practice
      development activities, benchmarking, knowledge pooling and translation through
      membership of a community of practice and a virtual college. METHODS: Twenty-four
      nurses, from 18 practice sites formed three communities of practice, each
      selecting evidence-based guidance to implement. A modified group supervision
      framework empowered nurses to champion local implementation. Outcomes were
      determined at 6 months. RESULTS: Eighty per cent of the patient-related criteria
      and 35% of the facilities criteria were achieved. The Revised Nursing Work Index
      indicated these nurses experienced greater autonomy (P = 0.019) and increased
      organizational support (P = 0.037). Focus groups revealed a deepening
      organizational support for the initiative over time, illuminated work-based
      learning challenges and overall enthusiasm for the approach. CONCLUSION:
      Implementation of the model effectively promoted evidence-based practice, most
      notably at the level of the individual patient. IMPLICATIONS FOR NURSING
      MANAGEMENT: Time and budgetary constraints necessitate smart, value for money
      approaches to developing evidence-based practice and improved care standards.
      This work demonstrates an effective model that strikes a balance between
      individual and group learning, virtual and real-time activities, coupled with
      resource pooling across organizations and sectors.

PMID- 18808463
TI  - Information technology from novice to expert: implementation implications.
AB  - AIMS: This paper explores how the Novice-to-Expert Nursing Practice framework can
      illuminate the challenges of and opportunities in implementing information
      technology (IT), such as clinical decision support systems (CDSS), in nursing
      practice. BACKGROUND: IT implementation in health care is increasing; however,
      substantial costs and risks remain associated with these projects. EVALUATION:
      The theoretical framework of Novice-to-Expert Nursing Practice was applied to
      current design and implementation literature for CDSS. KEY ISSUES: Organizational
      policies and CDSS design affect implementation and user adoption. CONCLUSIONS:
      Nursing CDSS can improve the overall quality of care when designed for the
      appropriate end-user group and based on a knowledge base reflecting nursing
      expertise. IMPLICATIONS FOR NURSING MANAGEMENT: Nurse administrators can
      positively influence CDSS function and end-user acceptance by participating in
      and facilitating staff nurse involvement in IT design, planning and
      implementation. Specific steps for nurse administrators and managers are included
      in this paper.

PMID- 18808464
TI  - Modernizing the school health workforce. Staff perceptions of a rapid roll-out
      redesign programme.
AB  - AIMS: To explore the perceptions of staff participating in an NHS school health
      workforce modernization rapid roll-out redesign programme. BACKGROUND: The health
      and well-being of children is central to national policy and focuses upon multi
      agency working. As part of the NHS modernization programme, a rapid roll-out
      workforce redesign model was developed for the school health workforce and
      introduced in northern England. METHODS: An evaluation approach using electronic
      distributed questionnaires and telephone interviews was utilized. RESULTS:
      Respondents reported that the approach was a valuable and fast way of introducing
      change to the workforce. Benefits for participants in providing networking
      opportunities were reported. LIMITATIONS OF THE STUDY: Data were collected from
      one programme and local factors may have influenced the findings. CONCLUSION: The
      rapid roll-out approach appears to be a successful way of introducing change to
      the school health workforce. IMPLICATIONS FOR NURSING MANAGEMENT: Workforce
      redesign using a rapid roll-out approach is a fast and effective approach,
      additionally providing benefits for staff participating in the process.

PMID- 18808465
TI  - The clinical content of NHS trust board meetings: an initial exploration.
AB  - OBJECTIVES: To differentiate between English NHS trust board meetings according
      to the percentage of clinical content and to explore which characteristics of
      board meetings might explain this. METHODS: Definition of scoring system for
      clinical content. Scoring of minutes for a random sample of 60 trusts.
      Qualitative analysis of a sub-sample, generated hypotheses about factors leading
      to higher percentage of clinical items was undertaken; testing of hypotheses in a
      longitudinal sample of minutes from 24 trusts over 1 year. RESULTS: Clinical
      content varied from 2% to 30%. Boards with a more clinical focus tended to link
      other issues including finance to clinical issues; have non-executive directors
      able to question board executives openly; make less use of acronyms in minutes;
      had more liaison with social services; and accepted questions from the public.
      CONCLUSIONS: Counting items in board minutes has prima facie validity as a means
      of defining how clinically focussed board meetings are, although more research is
      required to refine the method. The present method of analysing board minutes may
      provide one way of assessing board culture. IMPLICATIONS FOR NURSING MANAGEMENT:
      Directors of nursing can help focus trust board meetings on clinical matters.
      Further research is required to determine whether greater clinical content in
      trust board meetings has impacts on clinical practice or organizational
      performance.

PMID- 18808466
TI  - Job satisfaction among a multigenerational nursing workforce.
AB  - AIM: To explore generational differences in job satisfaction. BACKGROUND:
      Effective retention strategies are required to mitigate the international nursing
      shortage. Job satisfaction, a strong and consistent predictor of retention, may
      differ across generations. Understanding job satisfaction generational
      differences may lead to increasing clarity about generation-specific retention
      approaches. METHOD: The Ontario Nurse Survey collected data from 6541 Registered
      Nurses. Participants were categorized as Baby Boomer, Generation X or Generation
      Y based on birth year. Multivariate analysis of variance explored generational
      differences for overall and specific satisfaction components. RESULTS: In overall
      job satisfaction and five specific satisfaction components, Baby Boomers were
      significantly more satisfied than Generations X and Y. CONCLUSION: It is
      imperative to improve job satisfaction for younger generations of nurses.
      IMPLICATIONS FOR NURSING MANAGEMENT: Strategies to improve job satisfaction for
      younger generations of nurses may include creating a shared governance framework
      where nurses are empowered to make decisions. Implementing shared governance,
      through nurse-led unit-based councils, may lead to greater job satisfaction,
      particularly for younger nurses. Opportunities to self schedule or job share may
      be other potential approaches to increase job satisfaction, especially for
      younger generations of nurses. Another potential strategy would be to
      aggressively provide and support education and career-development opportunities.

PMID- 18808467
TI  - Addressing the turnover issue among new nurses from a generational viewpoint.
AB  - AIM: To investigate the relationship between dimensions of the psychosocial work
      environment and the intent to quit among a new generation of nurses. BACKGROUND:
      As a new generation of nurses enters the workforce, we know little about their
      perception of their current work environment and its impact on their intent to
      stay. METHOD: A self-administered questionnaire was distributed to 1002 nurses.
      RESULTS: The nurses who intended to quit their positions perceived a significant
      effort/reward imbalance as well as a lack of social support. The nurses who
      intended to quit the profession perceived a significant effort/reward imbalance,
      high psychological demands and elevated job strain. CONCLUSION: The balance
      between the level of effort expended and reward received plays an important role
      in young nurses' intent to leave. IMPLICATIONS FOR NURSING MANAGERS: Nurse
      Managers must offer Nexters, from the beginning of their career, a meaningful
      work and supportive environment. Without the efforts of the organization to
      improve the work environment and support nurses, this generation may not feel
      valued and move to another organization that will support them or another career
      that will offer fulfilment.

PMID- 18808468
TI  - An extra pair of hands? A case study of the introduction of support workers in
      community mental health teams for older adults.
AB  - BACKGROUND: Despite the expanding deployment of support workers in mental health
      services, little evidence exists on what managers and professional practitioners
      should expect of such staff in community settings. AIMS: This case study
      evaluated the introduction of support workers in community mental health teams
      for older adults. METHOD: A multiple method design engaged support workers and
      professional colleagues in individual interviews, a focus group and a work
      satisfaction survey. RESULTS: While the new resource boosted service provision,
      disparity between the intended role and the assumptions of professional
      practitioners caused confusion and dissatisfaction. CONCLUSIONS: The study
      highlights the need for managers to ensure role clarity when non-professional
      workers are introduced into multidisciplinary community teams. IMPLICATIONS FOR
      NURSING MANAGEMENT: Promoting diversity of skills in the mental health workforce
      is a progressive move in tuning services to the heterogenous needs of clients in
      the community. However, introducing unqualified workers into multi-disciplinary
      teams necessitates clear guidance to prevent their activity being confined within
      existing professional models. Support workers offer much potential in innovative
      service delivery.

PMID- 18808469
TI  - Are nurses prepared for retirement?
AB  - AIM: This study explored various factors and income sources that registered
      nurses believe are important in retirement planning. BACKGROUND: In many
      countries worldwide, many registered nurses are approaching retirement age. This
      raises concerns related to the level of preparedness of retiring nurses. METHODS:
      A mail-out questionnaire was sent to 200 randomly selected nurses aged 45 and
      older. SPSS descriptors were used to outline the data. Multiple t-tests were
      conducted to test for significant differences between selected responses by staff
      nurses and a group of nurse managers, educators and researchers. RESULTS: Of 124
      respondents, 71% planned to retire by age 60. Only 24% had done a large amount of
      planning. The top four planning strategies identified were related to keeping
      healthy and active, both physically and mentally; a major financial planning
      strategy ranked fifth. Work pensions, a government pension and a personal savings
      plan were ranked as the top three retirement income sources. No significant
      differences were found between the staff nurse and manager groups on any of the
      items. IMPLICATIONS FOR NURSING MANAGERS/CONCLUSIONS: The results of this study
      suggest that managers' preparation for retirement is no different from that of
      staff nurses. All nurses may need to focus more on financial preparation, and
      begin the process early in their careers if they are to have a comfortable and
      healthy retirement. Nurse managers are in a position to advocate with senior
      management for early and comprehensive pre-retirement education for all nurses
      and to promote educational sessions among their staff. Managers may find the
      content of this paper helpful as they work with nurses to help them better
      prepare for retirement. This exploratory study adds to the limited amount of
      research available on the topic.

PMID- 18808470
TI  - Impact of clinical leadership development on the clinical leader, nursing team
      and care-giving process: a case study.
AB  - AIM: This study explored the dynamics related to a leadership development
      programme and their impact on the clinical leader, the nursing team and the care
      giving process. BACKGROUND: While there is a growing conviction about the need to
      invest in transformational leadership in nursing, further insight into the true
      complexity of leadership development and, more specifically, how leadership can
      make a difference in nursing and patient outcomes is essential. METHOD: A single
      instrumental case study was conducted in a unit of a large academic hospital
      where a Clinical Leadership development Project (CLP) was implemented
      successfully. We used mixed methods with multiple sources of data to capture the
      complexity of leadership development. Data were collected through individual
      interviews, focus groups and observation of participants. A purposive sample of
      17 participants representing a wide variety of team members has permitted data
      saturation. The data were categorized and conceptualized and finally organized
      into a framework describing leadership development on the unit and its impact on
      the leader, the nursing team and the care-giving process. RESULTS: Leadership
      development is an ongoing, interactive process between the clinical leader and
      the co-workers. The head nurse became more effective in areas of self-awareness,
      communication skills, performance and vision. The nursing team benefited because
      more effective leadership promoted effective communication, greater
      responsibility, empowerment and job clarity. Improved clinical leadership seemed
      also to influence patient-centred communication, continuity of care and
      interdisciplinary collaboration. CONCLUSIONS: The results of the study give more
      insight into the processes underlying the leader's progress towards attaining a
      transformational leadership style and its impact on the team members. The impact
      of leadership on the care-giving process, however, remains difficult to describe.
      IMPLICATIONS FOR NURSING MANAGEMENT: The interactive nature of leadership
      development makes CLP a challenge for the leader as well for the team members.
      Through its impact on the leader and the nursing team, CLP is a valuable
      instrument for improving work environments of nurses, contributing positively to
      patient-centred care.

PMID- 18808471
TI  - Recruiting a diverse group of middle school girls into the trial of activity for
      adolescent girls.
AB  - BACKGROUND: School-based study recruitment efforts are both time consuming and
      challenging. This paper highlights the recruitment strategies employed by the
      national, multisite Trial of Activity for Adolescent Girls (TAAG), a study
      designed to measure the effectiveness of an intervention to reduce the decline of
      physical activity levels among middle school-aged girls. TAAG provided a unique
      opportunity to recruit large cohorts of randomly sampled girls within 36 diverse
      middle schools across the United States. METHODS: Key elements of the formative
      planning, coordination, and design of TAAG's recruitment efforts included
      flexibility, tailoring, and the use of incentives. Various barriers, including a
      natural disaster, political tension, and district regulations, were encountered
      throughout the recruitment process, but coordinated strategies and frequent
      communication between the 6 TAAG sites were helpful in tailoring the recruitment
      process at the 36 intervention and control schools. RESULTS: Progressively
      refined recruitment strategies and specific attention to the target audience of
      middle school girls resulted in overall study recruitment rates of 80%, 85%, and
      89%, for the baseline, posttest, and follow-up period, respectively. DISCUSSION:
      The steady increase in recruitment rates over time is attributed to an emphasis
      on successful strategies and a willingness to modify less successful methods.
      Open and consistent communication, an increasingly coordinated recruitment
      strategy, interactive recruitment presentations, and participant incentives
      resulted in an effective recruitment campaign.

PMID- 18808473
TI  - Schools and neighborhoods: organizational and environmental factors associated
      with crime in secondary schools.
AB  - BACKGROUND: While crime and violence in schools are derived primarily from
      factors external to schools, violent behavior may also be aggravated by factors
      in the school environment, including the physical environment, its educational
      and social climate, and its organizational capacity and composition. The
      objective of this study is to examine the effect of the school's organizational
      and educational environment on crime rates in secondary schools and to examine
      how neighborhood factors influence these relationships. METHODS: School and
      neighborhood crime rates for 95 middle (MS) and high (HS) schools were calculated
      using data from the Los Angeles Unified School District (LAUSD) Police Department
      and Los Angeles Police Department, respectively. School-level organizational and
      educational variables, including the academic performance index (API), were
      obtained from the California Department of Education. A measure of neighborhood
      dilapidation was created using variables collected on a neighborhood
      environmental survey. Linear regression was used to examine the relationship
      between organizational and educational school variables and school crime rates.
      Community crime and dilapidation were added to the model to examine the influence
      of the school-community context relationships. RESULTS: HS had higher crime rates
      than MS. As the percentage of certified teachers and student to staff ratios
      increased, school crime decreased (p < .01). An API of below basic performance
      was significantly associated with increasing school crime rates (p < .05).
      Neighborhood crime was not significantly associated with school crime, although
      dilapidation was positively and significantly associated with school crime even
      after controlling for community crime (p < .05). CONCLUSIONS: Both school- and
      neighborhood-level factors were associated with increasing crime rates in
      secondary schools. School violence prevention efforts should include school and
      community partnerships to address these potentially modifiable factors.

PMID- 18808472
TI  - Medicaid's role in financing health care for children with behavioral health care
      needs in the special education system: implications of the Deficit Reduction Act.
AB  - BACKGROUND: Recent changes to Medicaid policy may have unintended consequences in
      the education system. This study estimated the potential financial impact of the
      Deficit Reduction Act (DRA) on school districts by calculating Medicaid
      reimbursed behavioral health care expenditures for school-aged children in
      general and children in special education in particular. METHODS: Medicaid claims
      and special education records of youth ages 6 to 18 years in Philadelphia, PA,
      were merged for calendar year 2002. Behavioral health care volume, type, and
      expenditures were compared between Medicaid-enrolled children receiving and not
      receiving special education. RESULTS: Significant overlap existed among the
      126,533 children who were either Medicaid enrolled (114,257) or received special
      education (27,620). Medicaid-reimbursed behavioral health care was used by 21% of
      children receiving special education (37% of those Medicaid enrolled) and 15% of
      other Medicaid-enrolled children. Total expenditures were $197.8 million, 40% of
      which was spent on the 5728 children in special education and 60% of which was
      spent on 15,092 other children. CONCLUSIONS: Medicaid-reimbursed behavioral
      health services disproportionately support special education students, with
      expenditures equivalent to 4% of Philadelphia's $2 billion education budget. The
      results suggest that special education programs depend on Medicaid-reimbursed
      services, the financing of which the DRA may jeopardize.

PMID- 18808474
TI  - High school youth and suicide risk: exploring protection afforded through
      physical activity and sport participation.
AB  - BACKGROUND: Suicide ranks as the third leading cause of death for adolescents.
      Recent data from the Centers for Disease Control and Prevention (CDC) indicate
      that the adolescent suicide rate increased 18% between 2003 and 2004. Sport may
      represent a promising protective factor against adolescent suicide. This study
      examined the relative risk of hopelessness and suicidality associated with
      physical activity and sport participation. METHODS: Data from the CDC's 2005
      Youth Risk Behavior Survey were analyzed. Logistic regression modeling was used
      to compare the odds of hopelessness and suicidality in students who engaged in
      various levels of physical activity to inactive students. Similar analyses were
      performed comparing risks of athletes to nonathletes, and the risks of highly
      involved athletes to nonathletes. RESULTS: Findings showed that frequent,
      vigorous activity reduced the risk of hopelessness and suicidality among male
      adolescents. However, low levels of activity actually increased the risk of
      feeling hopeless among young females. Yet, for both males and females, sport
      participation protected against hopelessness and suicidality. CONCLUSION: These
      findings indicate that involvement in sport confers unique psychosocial benefits
      that protect adolescents against suicidality. Findings suggest that mechanisms
      other than physical activity contribute to the protective association between
      sport and reduced suicidality. Social support and integration may account for
      some of the differences found in suicidality between athletes and nonathletes.

PMID- 18808475
TI  - Violence and drug use in rural teens: national prevalence estimates from the 2003
      Youth Risk Behavior Survey.
AB  - OBJECTIVES: The purpose of this study was to compare national estimates of drug
      use and exposure to violence between rural and urban teens. METHODS: Twenty-eight
      dependent variables from the 2003 Youth Risk Behavior Survey were used to compare
      violent activities, victimization, suicidal behavior, tobacco use, alcohol use,
      and illegal drug use across rural, urban, and suburban teens across the country.
      RESULTS: Overall, rural teens were equally or more likely than both suburban and
      urban teens to report experiencing many measures of violent behavior,
      victimization, suicide behaviors, and drug use. Among all teens, nonwhites
      reported equal or higher rates of violent behavior and victimization than whites,
      but these associations disappeared within the rural-only population. CONCLUSIONS:
      Rural areas do not appear to provide a strongly protective effect against risk
      behaviors in teens and may be a risk factor in itself. Community prevention
      efforts should focus on reaching rural areas and segmenting program content based
      on need. Where white teens might benefit from an emphasis on preventing tobacco
      and alcohol use, nonwhite teens would benefit from an emphasis on preventing
      violence and victimization.

PMID- 18808476
TI  - A national snapshot of local school wellness policies.
AB  - BACKGROUND: The federal mandate for local wellness policies (LWP) provides an
      unprecedented opportunity to improve schools' practices that support student
      health, which, in turn, supports academic achievement. With a full agenda and
      budget challenges, districts need resources and support to turn policies into
      sustainable practices. The purpose of this study was to assess district policy
      goals and compare them to the federal mandate and benchmarks of best practices.
      It is hoped that this information will lead to development of specific assistance
      in the areas of policy implementation, evaluation, and revision. METHODS: Action
      for Healthy Kids (AFHK) collected a convenience sample of 256 approved LWP. The
      sample included districts with small, medium, and large student enrollment from
      every state (except Hawaii). Policies were compared to federal requirements and
      the AFHK Wellness Policy Fundamentals, a tool which documents best practices for
      nutrition and physical activity in schools. RESULTS: Sixty-eight percent of
      policies sampled were consistent with the mandates set forth in the law. Thirty
      two percent did not address 1 or more goal areas set by the federal mandate with
      15% not addressing goals for evaluation and monitoring. None of the policies
      addressed all components of AFHK's Fundamentals. Less than 1% addressed all 4 of
      the evaluation components. Teacher requirements and training for nutrition and
      physical education were addressed by 43% and 45% of policies, respectively.
      CONCLUSIONS: This study's findings indicate schools will need assistance to meet
      each of the mandates provided by the federal mandate. Areas lacking attention in
      policies, yet essential for sustaining wellness practices, include assurances of
      qualified staff, opportunities for staff development, and implementation,
      evaluation, and revision of the policy.

PMID- 18808481
TI  - Occupational therapy practice in rural and remote South Australia.

PMID- 18808482
TI  - Profile of occupational therapy practice in rural and remote South Australia.
AB  - OBJECTIVE: The aim of this report is to discuss the results of a questionnaire
      conducted with occupational therapists providing services in rural and remote
      South Australia. It is envisaged that the results will be of interest to health
      professionals working in country areas of Australia. The questionnaire aimed at
      capturing descriptive information from these therapists in regards to the type of
      services they deliver and the strategies they employ to deliver services,
      including information on human resources and staff retention. DESIGN AND METHODS:
      A questionnaire sent to occupational therapy managers and yielded a 44% response
      rate. RESULTS: Results provide descriptive information on the services provided,
      for example, the vast geographical areas covered. Respondents described the
      challenges they face in service delivery and these include the wide range of
      services to diverse client groups, high client-therapist ratio and limited human
      resources. Examples of strategies used are less labour-intensive service delivery
      models, multi-skilling of staff, networking and use of problem-solving
      techniques. Most perceived their services to be addressing client needs and they
      felt supported in their roles by other occupational therapists and their
      organisations. CONCLUSIONS: Occupational therapists working in rural and remote
      South Australia are overcoming the challenges identified in this questionnaire by
      implementing innovative strategies.

PMID- 18808483
TI  - Influences on medical students' decisions to study at a rural clinical school.
AB  - OBJECTIVE: To identify factors that influenced medical students at Monash
      University to undertake their first year of clinical training (third year of the
      medical course) at a rural clinical school (RCS). DESIGN: Third-year Monash
      University medical students undertaking clinical placements at a RCS were
      surveyed in 2005. A semistructured questionnaire was used to ask students to rate
      the influence of a list of factors on their decision to undertake their year-long
      placement at a RCS. RESULTS: Under half (48%) of students studying at an RCS
      reported that they were of rural background. All surveyed items were identified
      as having had a positive influence. Greater clinical experience, learning
      opportunities and patient access were identified as having the greatest positive
      influence followed closely by free accommodation and other financial and
      supportive incentives. Future rural career intention was eight times more likely
      to be a positive influence in rural compared with urban background students.
      CONCLUSION: The most important positive influence on Monash third-year medical
      students' decision to study at an RCS is the perception of high-quality clinical
      experiences and education. This perception arises from rural exposure during pre
      clinical years.

PMID- 18808484
TI  - Geographical variation of incidence of cutaneous melanoma in Queensland.
AB  - OBJECTIVE: The study investigated geographical differences and time trends of
      incidence rate and body site distribution of cutaneous melanoma in Queensland.
      DESIGN: Analysis of data recorded by Queensland Cancer Registry. PATIENTS:
      Analysis included 34 021 patients with invasive and 10 710 patients with in situ
      melanoma diagnosed between 1982 and 2002. MAIN OUTCOME MEASURES: Age-standardised
      incidence rates (world standard population) per 100 000 inhabitants of cutaneous
      melanoma and annual percentage change (APC). RESULTS: Yearly age-standardised
      incidence rates of invasive melanoma averaged over the 21 years of observation
      were highest in the south-eastern part of the state, notably in the statistical
      division Moreton for men (54.2) and in Fitzroy for women (51.4). Inland divisions
      had on average lower rates than coastal areas. For both men and women, age
      standardised incidence rates of invasive and of in situ melanoma increased
      between 1982 and 2002 for Queensland as a whole and for almost all its
      statistical divisions. For invasive cancer, the increase was strongest for
      Moreton (APC men: 5.4%; women: 4.5%; P < 0.001, respectively). APCs were higher
      for in situ melanoma compared with invasive melanoma for all statistical
      divisions and both genders. In both genders, the increase in invasive rates was
      most pronounced for the trunk (APC men: 3.2%, P = 0.040; women: 2.3%; P = 0.306).
      CONCLUSIONS: The south-eastern corner of Queensland endured the main burden of
      melanoma. Behavioural and lifestyle choices might create the observed differences
      between statistical divisions. The increase in trunk melanomas is discussed with
      respect to aetiology.

PMID- 18808485
TI  - Physical activity of young people in the Torres Strait and Northern Peninsula
      Region: an exploratory study.
AB  - OBJECTIVE: The present study explored the practices of, and perceived barriers
      to, physical activity of young people living in remote communities in the Torres
      Strait and Northern Peninsula Area of Far North Queensland. DESIGN AND SETTING: A
      cross-sectional survey exploring physical activity practices of children
      attending primary and secondary schools in two communities in the Torres Strait,
      Far North Queensland. PARTICIPANTS: A total of 367 primary and secondary school
      aged children (aged 9-16 years). MAIN OUTCOME MEASURES: Only 50% of the children
      reported being active for more than 30 min a day and approximately 25% of both
      primary and high school children surveyed were 'pretty much active only at week
      ends'. The major barriers cited to being active were related to the climate, lack
      of equipment and child-specific activities and low self-perception of ability.
      CONCLUSIONS: A large proportion of school students in the Torres Strait and
      Northern Peninsula Area reported low levels of physical activity. The main
      barriers cited to being active suggest that structural and family-based
      strategies are required to help young people, especially girls, to engage in more
      physical activity. There is also a need for skills and confidence-building
      activities delivered in a non-competitive environment for those who feel that
      they lack the necessary skills to participate fully.

PMID- 18808486
TI  - The oral health status and treatment needs of Indigenous adults in the Kimberley
      region of Western Australia.
AB  - OBJECTIVE: The oral health of Indigenous Australians, whether urban or rural, is
      significantly poorer than their non-Indigenous counterparts, and it would be
      expected that the oral health of rural and remote Indigenous Australians would be
      particularly poor, although the extent of this extra disadvantage has not been
      thoroughly documented. The aim of this study was to assess the oral health status
      and oral health needs in a sample of adult residents of selected towns and remote
      communities in the Kimberley region of North-west Australia. DESIGN: A cross
      sectional survey (dental examinations and oral health questionnaires) was carried
      out. SETTING: Rural and remote communities in the Kimberley region of Western
      Australia. PARTICIPANTS: Adults in four selected communities. RESULTS: The mean
      Decayed, Missing and Filled Teeth (DMFT) score for all participants was 9.8 (SD
      8.3). The mean DMFT increased with increasing age. Only 7.3% of people were
      caries-free. A total of 13% of participants had periodontal pockets of 6 mm or
      more, and only 3% had no periodontal disease. More than a third (37%) of all
      participants had advanced periodontal disease. Only 21% of participants did not
      need any dental treatment. CONCLUSIONS: The oral health of Aboriginal and Torres
      Strait Islander people are listed as one of the priority areas of Australia's
      National Oral Health Plan. Based on the above results, oral health is clearly an
      important priority in the Kimberley.

PMID- 18808487
TI  - Subjective well-being, sociodemographic factors, mental and physical health of
      rural residents.
AB  - OBJECTIVE: To ascertain the relationship between subjective well-being and
      sociodemographic factors, mental and physical health of a sample of rural
      residents. DESIGN: Cross-sectional survey with stratified random sampling of
      persons based on the 2000 State Electoral Role. Questionnaire was forwarded to 23
      000 residents throughout a rural area. SETTING: Households within Gippsland.
      PARTICIPANTS: Five thousand three hundred and ninety-one adults aged 18 years and
      above. MAIN OUTCOME MEASURES: Residents completed a self-reported questionnaire
      assessing life satisfaction/subjective well-being, psychological distress,
      sociodemographic factors, physical and mental health problems. RESULTS: Completed
      survey indicated that participants with lower levels of psychological distress,
      physical disability and mental disability had higher odds of being satisfied with
      their life. Participants with severe mental disability had the lowest odds of
      being satisfied with life. On average, participants were satisfied with their
      life (mean score of 21, SD = 5.9), are within the normal range of the Kessler-10
      (mean score = 16.31, SD = 5.85), had no mental disability (mean score = 51.8, SD
      = 7.36) on the mental component of the Short Form-12 Health Survey, but are
      mildly physically disabled (mean score = 48.9, SD = 7.74). CONCLUSIONS: The
      results of this study indicate that sociodemographic factors, psychological
      distress, physical health and mental health contribute to subjective well-being.
      Compared with other age groups, those aged 66 years and above had the highest
      level of life satisfaction. Those living with partner/spouse without children,
      with no mental or physical disability and no psychological distress had highest
      level of life satisfaction. Women also had higher levels of life satisfaction
      compared with men.

PMID- 18808488
TI  - Increasing community participation in an Aboriginal health service.
AB  - OBJECTIVE: To increase Aboriginal participation with mainstream health
      professionals in an Aboriginal health and well-being centre. DESIGN:
      Participatory Action Research using Aboriginal traditional symbolism to depict
      aspects of the research process, interview surveys and a document review.
      SETTING: A regional town with 629 Aboriginal and Torres Strait Islander residents
      and a newly established Aboriginal health and well-being centre (Nunyara).
      PARTICIPANTS: Thirty Aboriginal community members were interviewed about their
      involvement with Nunyara and their health issues. Participants were selected
      through purposive 'pass-me-around' sampling to ensure that all family groups were
      included. RESULTS: The results are presented in two areas: the structure of the
      Aboriginal community that affects participation and community views about health
      issues. Aboriginal people living in the town come from 10 or more different
      language groups and relate almost exclusively within their own groups. Activities
      at Nunyara were seen as individual family group events and not for everyone.
      Aboriginal community participants had a broad view of health as they reported
      problems that included smoking and alcohol use. Almost all would like more
      involvement in health issues through Nunyara. CONCLUSION: Aboriginal community
      members are willing to get involved in health issues in collaboration with
      Nunyara. However, fundamental to increasing participation is to bring people
      together from different family groups and increase social cohesion. This can be
      done through developing relationships with groups enabling different points of
      view to be heard and valued.

PMID- 18808489
TI  - Health knowledge acquisition by rural women with chronic health conditions: a
      tale of two Web approaches.
AB  - OBJECTIVES: To determine the differences in health knowledge acquisition and the
      perceived impact on self-management of chronic illness provided by two approaches
      to providing Web-based information. DESIGN: Repeated-measure questionnaire
      administered at four time points: baseline, 11, 23 and 53 weeks; a post-computer
      intervention survey. SETTING AND PARTICIPANTS: One hundred and seventy-six
      chronically ill women (aged 32-68 years) living in rural areas. MAIN OUTCOME
      MEASURES: Scores on knowledge questions within repeated measures; participant
      ratings on perceptions of abilities to self-manage. INTERVENTION: The 22-week
      computer-based intervention provided online support and health information. Women
      were randomly assigned to an intense intervention (n = 54), less-intense
      intervention (n = 58) or control group (n = 64). RESULTS: Both computer
      intervention groups gained significantly in health knowledge with little
      differential effect at intervention conclusion or after 6 months, when there was
      a drop-off in health knowledge retention of about one-third (intense - baseline
      mean = 0.54, week 23 = 0.69, week 53 = 0.65; less intense - 0.58, 0.68, 0.65).
      Control remained about the same (0.51, 0.51, 0.53). Using an anova analysis,
      there was no appreciable difference between intervention groups in perceptions of
      ability to self-manage illness (intense - mean = 4.02 (on a scale of 1-6),
      standard deviation = 0.99); less intense - (mean = 3.85, standard deviation =
      1.00), t(107) = 0.90, P = 0.37). CONCLUSIONS: A less-intense intervention can be
      as effective as a more complex, labour-intensive and costly intervention in
      assisting chronically ill rural women to acquire health knowledge they consider
      to be moderately helpful in managing their chronic conditions.

PMID- 18808490
TI  - Royal Flying Doctor Service 'field days': a move towards more comprehensive
      primary health care.
AB  - OBJECTIVE: To examine the Royal Flying Doctor Service (RFDS) field day program as
      a means of strengthening community capacity within a primary health care context
      in remote communities of north Queensland. DESIGN: Qualitative explanatory study
      using in-depth face-to-face and phone interviews with field day participants,
      field day coordinators and RFDS staff and a focus group with RFDS staff. SETTING:
      Rural and remote communities of north Queensland that participate in RFDS field
      days. RESULTS: Field days were found to be contributing to building capacity for
      health in the remote communities that have been involved in field days.
      Participants reported increased linkages and partnerships; increased
      participation; improved problem-solving capacity and increased knowledge transfer
      associated with the conduct of RFDS field days. CONCLUSION: RFDS field days
      represent a viable framework for building community capacity for health in remote
      communities within a primary health care context.

PMID- 18808491
TI  - Improving mental health capacity in rural communities: mental health first aid
      delivery in drought-affected rural New South Wales.
AB  - OBJECTIVE: To assess the effectiveness of mental health first aid (MHFA) training
      in drought-affected rural and remote Australia, as part of a strategy to improve
      capacity among farming communities to provide early intervention for mental
      health problems. METHODS: Data were obtained from 99 participants recruited
      across 12 New South Wales towns, before and after delivery of MHFA seminars
      emphasising the role of front-line workers from agricultural-related services.
      Surveys assessed knowledge of, confidence in dealing with, and attitude towards
      people experiencing mental illness, along with the impact of training on response
      to mental health problems among target population of farmers and farming
      families. RESULTS: Rural support workers and community volunteers attended MHFA
      seminars because of perceived mental health needs in the workplace. A majority of
      responses reflect a concern with giving appropriate advice and support well
      outside narrow job definitions. Participants' ability to identify high prevalence
      disorders and endorse evidence-based interventions for both high and low
      prevalence disorders increased following MHFA training, as did their confidence
      in their ability to provide appropriate help. CONCLUSIONS: MHFA training can form
      an effective part of a strategy to improve systems of care and pathways to early
      intervention in rural communities by using local networks to provide mental
      health support.

PMID- 18808492
TI  - Rurability: community support for rural families managing acquired brain injury.

PMID- 18808493
TI  - PHC RIS: health for all or health for some? Remembering Alma Ata.

PMID- 18808494
TI  - Community work injuries: country style.

PMID- 18808495
TI  - SARRAH: provision of allied health services to regional and remote Aboriginal and
      Torres Strait Islander communities.

PMID- 18808496
TI  - Commentary on Losos (2008): niche conservatism deja vu.

PMID- 18808500
TI  - Acute migraine medications and evolution from episodic to chronic migraine: a
      longitudinal population-based study.
AB  - BACKGROUND: Though symptomatic medication overuse is believed to play a major
      role in progression from episodic to chronic or transformed migraine (TM),
      population-based longitudinal data on these agents are limited. OBJECTIVES: To
      assess the role of specific classes of acute medications in the development of TM
      in episodic migraine (EM) sufferers after adjusting for other risk factors for
      headache progression. METHODS: As a part of the American Migraine Prevalence and
      Prevention study (AMPP), we initially surveyed a population sample of 120,000
      individuals to identify a sample of migraineurs to be followed annually over 5
      years. Using logistic and linear regression, we modeled the probability of
      transition from EM in 2005 to TM in 2006 in relation to medication use status at
      baseline. Adjustments were made for gender, headache frequency and severity, and
      prevention medication use. RESULTS: Of 8219 individuals with EM in 2005, 209
      (2.5%) had developed TM by 2006. Baseline headache frequency was a risk factor
      for TM. Using acetaminophen user as the reference group, individuals who used
      medications containing barbiturates (OR = 2.06, 95%CI = 1.3-3.1) or opiates (OR =
      1.98, 95%CI = 1.4-2.2) were at increased risk of TM. A dose-response relationship
      was found for use of barbiturates. Use of triptans (OR = 1.25, 95%CI = 0.9-1.7)
      at baseline was not associated with prospective risk of TM. Overall, NSAIDs (OR =
      0.85, 95%CI = 0.63-1.17) were not associated with TM. Indeed, NSAIDs were
      protective against transition to TM at low to moderate monthly headache days, but
      were associated with increased risk of transition to TM at high levels of monthly
      headache days. CONCLUSION: EM sufferers develop TM at the rate of 2.5% per year.
      Any use of barbiturates and opiates was associated with increased risk of TM
      after adjusting for covariates, while triptans were not. NSAIDs were protective
      or inducers depending on the headache frequency.

PMID- 18808501
TI  - Images from headache: cluster-like headache associated with intra-cavernous
      carotid artery thrombosis.

PMID- 18808502
TI  - Expert opinion: posttraumatic headaches among United States soldiers injured in
      Afghanistan and Iraq.

PMID- 18808503
TI  - Another comment on "Drug induced refractory headache".

PMID- 18808505
TI  - Headache and sexual activity: a review.

PMID- 18808506
TI  - Clinical and preclinical rationale for CGRP-receptor antagonists in the treatment
      of migraine.
AB  - Calcitonin gene-related peptide (CGRP) is linked to migraine and other primary
      headache disorders. It is found in every location described in migraine genesis
      and processing, including meninges, trigeminal ganglion, trigeminocervical
      complex, brainstem nuclei, and cortex. It is released in animal models following
      stimulation of the CNS similar to that seen in migraine, and triptans inhibit
      this release. Injection of CGRP into migraineurs results in delayed headache
      similar to migraine. Elevation of CGRP occurs during migraine, resolving
      following migraine-specific treatment. Finally, and most importantly, CGRP
      receptor antagonists terminate migraine with efficacy similar to triptans. Both
      intravenous olcegepant (BIBN 4096 BS) and oral telcagepant (MK-0974) have been
      effective, safe, and well tolerated in phase I and II studies. Telcagepant is
      currently in phase III trials, and preliminary results are favorable. The
      potential for a migraine-specific medication without vasoconstrictive or vascular
      side effects is enormous. CGRP receptor blockade may also have applications in
      other pathologic and pain syndromes.

PMID- 18808510
TI  - Compound medications for acute migraine treatment.

PMID- 18808507
TI  - Inhibition of calcitonin gene-related peptide function: a promising strategy for
      treating migraine.
AB  - The neuropeptide calcitonin gene-related peptide (CGRP) is implicated in the
      underlying pathology of migraine. Serum levels of CGRP, which are elevated during
      a migraine attack, have been reported to return to normal with alleviation of
      pain. In addition, CGRP administration has been shown to cause a migraine-like
      headache in susceptible individuals. Importantly, CGRP receptors are found on
      many cell types within the trigeminovascular system that are thought to play
      important roles in controlling inflammatory and nociceptive processes. Based on
      these findings, it was proposed that blockage of CGRP receptor function and,
      hence, the physiological effects of CGRP would be effective in aborting a
      migraine attack. This review will summarize key preclinical data that support the
      therapeutic potential of using CGRP receptor antagonists or molecules that bind
      CGRP within the context of current neurovascular theories on migraine pathology.

PMID- 18808511
TI  - Transforming community health services: English lessons on not relying on
      organisational reform.

PMID- 18808512
TI  - Older people--recipients but also providers of informal care: an analysis among
      community samples in the Republic of Ireland and Northern Ireland.
AB  - Data on both the provision and receipt of informal care among populations of
      older adults are limited. Patterns of both informal care provided and received by
      older adults in the Republic of Ireland (RoI) and Northern Ireland (NI) were
      evaluated. A cross-sectional community-based population survey was conducted.
      Randomly selected older people (aged 65+, n = 2033, mean age (standard
      deviation): 74.1 years (6.8), 43% men, 68% response rate) provided information on
      the provision and receipt of care, its location, and the person(s) who provided
      the care. Twelve per cent of the sample (251/2033) identified themselves as
      informal caregivers (8% RoI and 17% NI). Caregivers were more likely to be women,
      married, have less education and have less functional impairment. Forty-nine per
      cent (1033/2033, 49% RoI and 48% NI) reported receiving some form of care in the
      past year. Care recipients were more likely to be older, married, have more
      functional impairment, and poorer self-rated health. Receiving regular informal
      care (help at least once a week) from a non-resident relative was the most common
      form of help received [28% overall (578/2033); 27% RoI and 30% NI]. Five per cent
      (n = 102/2033) of the sample reported both providing and receiving informal care.
      Levels of informal care provided by community-dwelling older adults were notably
      higher than reported in single-item national census questions. The balance of
      formal and informal health and social care will become increasingly important as
      populations age. It is essential, therefore, to evaluate factors facilitating or
      impeding informal care delivery.

PMID- 18808524
TI  - Cellular expression of Bcl-2 and Bax in atrophic submandibular glands of rats.
AB  - In submandibular gland atrophy, most acinar cells disappear by apoptosis, while
      many duct cells remain. The present study aimed to establish whether Bcl-2 and
      Bax, members of the Bcl-2 gene family, regulating the signalling pathway of
      apoptosis were involved in duct cell survival and acinar cell death in atrophic
      submandibular glands. The excretory duct of rat submandibular gland was doubly
      ligated with metal clips from 1 to 14 days to induce atrophy to the gland. The
      expressions of Bcl-2 and Bax in the atrophic submandibular gland were examined
      using immunohistochemistry and reverse transcriptase-polymerase chain reaction
      (RT-PCR). Immunohistochemically, Bcl-2 expression was identified in duct cells in
      the experimental glands at all time points. Some acinar cells showed Bax
      positivity 1 day after excretory duct ligation, and there were more Bax-positive
      acinar cells on days 3 and 5 when many apoptotic acinar cells were observed.
      Analysis by RT-PCR showed that the expression of mRNA for Bcl-2 became stronger
      as the glandular atrophy progressed and that Bax mRNA strongly expressed on days
      1 and 3. These observations suggest that Bcl-2 inhibits duct cell apoptosis and
      Bax promotes apoptosis of acinar cells during atrophy of submandibular glands.

PMID- 18808525
TI  - A role of fukutin, a gene responsible for Fukuyama type congenital muscular
      dystrophy, in cancer cells: a possible role to suppress cell proliferation.
AB  - Fukutin, a gene responsible for Fukuyama type congenital muscular dystrophy
      (FCMD), is presumably related to the glycosylation of alpha-dystroglycan (alpha
      DG), involved in basement membrane formation. Hypoglycosylation of alpha-DG plays
      a key role for the pathogenesis of FCMD. On the other hand, fukutin and alpha-DG
      are also expressed in various non-neuromuscular tissues. Recently, a role of
      alpha-DG as a cancer suppressor has been proposed, because of a decrease of
      glycosylated alpha-DG in cancers. In this study, function of fukutin was
      investigated in two cancer cell lines, focusing on whether fukutin is involved in
      the glycosylation of alpha-DG in cancer cells and has any possible roles related
      to a cancer suppressor. Localization of fukutin and a result of laminin-binding
      assay after RNA interference suggest that fukutin may be involved in the
      glycosylation of alpha-DG in a small portion in these cancer cell lines. In
      Western blotting and immuno-electron microscopy, localization of fukutin in the
      nucleus was suggested in addition to the Golgi apparatus and/or endoplasmic
      reticulum. Immunohistochemically, there were more Ki-67-positive cells and more
      nuclear staining of phosphorylated c-jun after knockdown of fukutin in two cell
      lines. Fukutin appears to suppress cell proliferation through a system involving
      c-jun, although it is unclear this process is related to alpha-DG or not at
      present. The result may propose a possibility of another function of fukutin in
      addition to the glycosylation of alpha-DG in cancer cells.

PMID- 18808526
TI  - Intratubular transplantation as a strategy for establishing animal models of
      testicular germ cell tumours.
AB  - Testicular germ cell tumours (TGCTs) are prevalent cancers among young men.
      Currently, there is no reliable animal model for TGCTs. To establish such animal
      models, we have explored the possibility of intratubular testicular
      transplantation as means to deliver tumour cells into the seminiferous tubules of
      host animals. Our results demonstrated that transplanted cells could effectively
      populate the testis of a recipient mouse and develop into TGCTs. In addition, the
      donor cells could be transfected with a specific transgene before
      transplantation, thereby providing an approach to evaluate the specific effects
      of gene functions in the oncogenic processes. Hence, depending on selection of
      specific donor cells or mixtures of donor cells, transplantation models of TGCTs
      could be significant for studies on the pathogenesis, diagnosis and therapies of
      such a prevalent and important cancer in men.

PMID- 18808527
TI  - Temporal evolution of epithelial, vascular and interstitial lung injury in an
      experimental model of idiopathic pulmonary fibrosis induced by butyl
      hydroxytoluene.
AB  - This study was undertaken to test whether the structural remodelling of pulmonary
      parenchyma can be sequentially altered in a model and method that demonstrate the
      progression of the disease and result in remodelling within the lungs that is
      typical of idiopathic pulmonary fibrosis. Three groups of mice were studied: (i)
      animals that received 3-5-di-tert-butyl-4-hydroxytoluene (BHT) and were killed
      after 2 weeks (early BHT = 9); (ii) animals that received BHT and were killed
      after 4 weeks (late BHT = 11); (iii) animals that received corn oil solution
      (control = 10). The mice were placed in a ventilated Plexiglas chamber with a
      mixture of pure humidified oxygen and compressed air. Lung histological sections
      underwent haematoxylin-eosin, immunohistochemistry (epithelial, endothelial and
      immune cells) and specific staining (collagen/elastic fibres) methods for
      morphometric analysis. When compared with the control group, early BHT and late
      BHT groups showed significant decrease of type II pneumocytes, lower vascular
      density in both and higher endothelial activity. CD4 was increased in late BHT
      compared with early and control groups, while CD8, macrophage and neutrophil
      cells were more prominent only in early BHT. The collagenous fibre density were
      significantly higher only in late BHT, whereas elastic fibre content in late BHT
      was lower than that in control group. We conclude that the BHT experimental model
      is pathologically very similar to human usual interstitial pneumonia. This
      feature is important in the identification of animal models of idiopathic
      pulmonary fibrosis that can accurately reflect the pathogenesis and progression
      of the human disease.

PMID- 18808528
TI  - Adverse effect of the anabolic-androgenic steroid mesterolone on cardiac
      remodelling and lipoprotein profile is attenuated by aerobicz exercise training.
AB  - Abuse of anabolic-androgenic steroids (AAS) for improving physical performance is
      associated with serious, sometimes fatal, adverse effects. The aim of the present
      work was to investigate the effects of AAS on the cardiac structure and the
      plasma lipoprotein profile isolated and in combination with exercise. Transgenic
      mice with a human lipaemic phenotype (expressing cholesteryl ester transfer
      protein on the LDL receptor knockout background) were used in this study.
      Sedentary and exercised mice (treadmill running, five times per week for 6 weeks)
      were treated with mesterolone (2 microg/g body weight) or vehicle (control-C) in
      the last 3 weeks. Four groups were compared: (i) exercise + mesterolone (Ex-M),
      (ii) exercise + vehicle (Ex-C), (iii) sedentary + mesterolone (Sed-M) and (iv)
      sedentary + vehicle (Sed-C). Arterial blood pressure and body mass increased in
      all groups along time, but Sed-M reached the highest values and Ex-C the lowest.
      Treatment with mesterolone increased total cholesterol, triglyceride, low-density
      lipoprotein cholesterol (LDL-c) and very LDL-c (VLDL-c) plasma levels. However,
      exercise blunted some of these deleterious effects by increasing high-density
      lipoprotein cholesterol and decreasing LDL-c, VLDL-c and triglycerides. Exercise
      training induced beneficial effects, such as physiological cardiomyocyte
      hypertrophy, increase in myocardial circulation and decrease in cardiac
      interstitium. However, mesterolone impaired such physiological gains and in
      addition increased troponin T plasma levels both in sedentary and exercised mice.
      Thus, while mesterolone induced pro-atherogenic lipoprotein profile and
      pathogenic cardiac hypertrophy, exercise counteracted these effects and modified
      favourably both the lipoprotein profile and the cardiac remodelling induced by
      mesterolone.

PMID- 18808529
TI  - Isoproterenol induces primary loss of dystrophin in rat hearts: correlation with
      myocardial injury.
AB  - The mechanism of isoproterenol-induced myocardial damage is unknown, but a
      mismatch of oxygen supply vs. demand following coronary hypotension and
      myocardial hyperactivity is the best explanation for the complex morphological
      alterations observed. Severe alterations in the structural integrity of the
      sarcolemma of cardiomyocytes have been demonstrated to be caused by
      isoproterenol. Taking into account that the sarcolemmal integrity is stabilized
      by the dystrophin-glycoprotein complex (DGC) that connects actin and laminin in
      contractile machinery and extracellular matrix and by integrins, this study tests
      the hypothesis that isoproterenol affects sarcolemmal stability through changes
      in the DGC and integrins. We found different sensitivity of the DGC and integrin
      to isoproterenol subcutaneous administration. Immunofluorescent staining revealed
      that dystrophin is the most sensitive among the structures connecting the actin
      in the cardiomyocyte cytoskeleton and the extracellular matrix. The sarcomeric
      actin dissolution occurred after the reduction or loss of dystrophin.
      Subsequently, after lysis of myofilaments, gamma-sarcoglycan, beta-dystroglycan,
      beta1-integrin, and laminin alpha-2 expressions were reduced followed by their
      breakdown, as epiphenomena of the myocytolytic process. In conclusion,
      administration of isoproterenol to rats results in primary loss of dystrophin,
      the most sensitive among the structural proteins that form the DGC that connects
      the extracellular matrix and the cytoskeleton in cardiomyocyte. These changes,
      related to ischaemic injury, explain the severe alterations in the structural
      integrity of the sarcolemma of cardiomyocytes and hence severe and irreversible
      injury induced by isoproterenol.

PMID- 18808530
TI  - L-arginine ameliorates experimental autoimmune myocarditis by maintaining
      extracellular matrix and reducing cytotoxic activity of lymphocytes.
AB  - It was previously shown that administration of the nitric oxide synthase
      inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) aggravated murine viral
      myocarditis by increasing myocardial virus titres. Experimental autoimmune
      myocarditis in mice and rats mimics human fulminant myocarditis. The effects of L
      arginine, a precursor of nitric oxide, upon heart failure in experimental
      autoimmune myocarditis were evaluated. Dietary L-arginine (L-arginine group) and
      L-arginine plus N(G)-nitro-L-arginine methyl ester (L-arginine + l-NAME group)
      were administered to C57BL/6 mice immunized with porcine cardiac myosin over 3
      weeks. An untreated myocarditis group was prepared. Cardiac damage was less in
      the L-arginine group compared with the other two groups, as was incidence of
      heart failure. In addition, extracellular matrix change was less prominent in the
      L-arginine group. Plasma concentrations of nitric oxide were elevated in the L
      arginine group. Cytotoxic activities of lymphocytes were lower in L-arginine
      group than in other two groups. L-arginine treatment may be effective in
      preventing the development of heart failure in experimental myocarditis by
      maintaining extracellular matrix and reducing the cytotoxic activity of
      lymphocytes.

PMID- 18808532
TI  - Hospital avoidance: in whose interest?

PMID- 18808531
TI  - Role of inflammation in right ventricular damage and repair following
      experimental pulmonary embolism in rats.
AB  - Right ventricular (RV) dysfunction is associated with poor clinical outcome
      following pulmonary embolism (PE). Previous studies in our laboratory show that
      influx of neutrophils contributes to acute RV damage seen in an 18 h rat model of
      PE. The present study describes the further progression of inflammation over 6
      weeks and compares the neutrophil and monocyte responses. The RV outflow tract
      became white in colour by day 1 with influx of neutrophils (tissue
      myeloperoxidase activity increased 17-fold) and mononuclear cells with
      characteristics of M1 phenotype (high in Ccl20, Cxcl10, CcR2, MHCII, DNA
      microarray analysis). Matrix metalloproteinase activities were increased and
      tissue was thinned to produce a translucent appearance in weeks 1 through 6 in
      40% of hearts. RV contractile function was significantly reduced at 6 weeks of
      PE. In this later phase, there was accumulation of myofibroblasts, the presence
      of mononuclear cells with M2 characteristics (high in scavenger mannose
      receptors, macrophage galactose lectin 1, PDGFR1, PDGFRbeta), enrichment of the
      subendocardial region of the RV outflow tract with neovesels (alpha-smooth muscle
      immunohistochemistry) and deposition of collagen fibres (picrosirius red
      staining) beginning scar formation. Thus, while neutrophil response is associated
      with the early, acute inflammatory events, macrophage cells continue to be
      present during the proliferative phase and initial deposition of collagen in this
      model, changing from the M1 to the M2 phenotype. This suggests that the
      macrophage cell response is biphasic.

PMID- 18808533
TI  - Truth-telling, honesty and compassion: a virtue-based exploration of a dilemma in
      practice.
AB  - In this paper a discussion of the strengths of a virtue-based approach to ethics
      in nursing is discussed. Virtue ethics is often depicted as vague and lacking in
      any convincing application to the reality of practice. It is argued that
      exploring issues from a virtue perspective offers the possibility of a sensitive
      moral response which is grounded in the context of the client and his family. Far
      from being vague, virtue ethics offers guidance in practice, but this guidance
      acknowledges the complexity of individual lives as opposed to the impartiality
      and abstract nature of traditional moral theory, rules and principles. The
      vehicle for discussion is a case in practice. The position presented here is that
      in taking account of the salient features of each individual case, withholding
      the truth from adults with a life threatening illness can be justified for
      compassionate reasons.

PMID- 18808534
TI  - The cultural-ecological orientation of graduate nurses (novice) in medical
      surgical nursing.
AB  - The aim of this research was to understand the process of clinical reasoning and
      decision-making and the impact that trajectory of experience has on the decision
      making of graduate nurses by investigating the clinical practice of 10 novice
      nurses. An ethnographic interpretive approach was used to study the clinical
      practice of novice nurses in medical-surgical nursing. An in-depth interview was
      conducted following the periods of observation. The findings of this research
      demonstrate that the graduates who participated in this study were instrumental
      in creating a cultural-ecological orientation to their practice, and inherent in
      their practice was a highly developed perceptual awareness of the individual
      needs of patients and their families, which resulted in a close bond with their
      patients.

PMID- 18808535
TI  - A comparison of patients' and nurses' assessments of pain intensity in patients
      with coronary artery disease.
AB  - Self-report of pain is the single most reliable indicator of pain intensity. The
      purpose of this study was to compare patients' and nurses' ratings of patients'
      pain. The sample comprised 76 patients and 65 nurses in coronary care units that
      rated the patient's pain intensity on a 0-10 numeric rating scale. Results showed
      that the mean scores of nurses were lower than their patients significantly (P <
      0.01). Also, nurses assessed patients' pain intensity accurately 60% of the time.
      Overestimations and underestimations were 12.4% and 27.6% respectively. In
      addition, there were positive, moderate and significant correlations between
      patients' and nurses' ratings (r = 0.41, P < 0.001). Underestimation of patient's
      pain can have negative effects if appropriate treatment is withheld. This
      emphasizes the importance of a systematic assessment and acceptance of the
      patient's self-reported of pain.

PMID- 18808536
TI  - Nurses' work environment and nursing outcomes: a survey study among Finnish
      university hospital registered nurses.
AB  - The aim was to assess the interrelationships between nurses' work environment and
      nursing outcomes. A cross-sectional survey of 664 registered nurses (RN) on 34
      acute care inpatient hospital wards was used to measure nurses' perceptions.
      Patient data (n = 4045) consisting of a total patient satisfaction indicator were
      collected simultaneously with the nurse data during year 2005. RN's assessments
      of staffing adequacy, respect and relationships were the most important factors
      of work environment having an influence on job-related stress, job satisfaction,
      patient satisfaction and adverse events to patients and nurses. Some 77% of the
      RN reported adverse nurse events and 96% reported adverse patient events during a
      3 month retrospective period. Ensuring sufficient and suitably qualified nurses'
      availability in delivering nursing care is an important management issue. Nurses
      are concerned about the quality of care, and the concerns perceived by nurses can
      influence their clinical work.

PMID- 18808537
TI  - Nursing practice environment: how does one Australian hospital compare with
      magnet hospitals?
AB  - Magnet hospitals are recognized institutions of nursing excellence that provide
      an environment for the promotion of nursing and high-quality patient care. The
      Magnet Recognition Program, developed by the American Nurses Credentialing
      Centre, acknowledges health-care institutions that not only attract and retain
      nursing staff but also recognize nursing excellence in the delivery of quality
      patient care. Our study aimed to adapt the existing Practice Environment Scale to
      the Australian context and to pilot its use in measuring the nursing practice
      environment at a metropolitan hospital in Sydney, Australia. Nursing staff from
      four wards at a 400 bed major metropolitan acute general hospital in Sydney,
      Australia completed a self-administered questionnaire about their practice
      environment. Data were compared with the published norms from magnet and non
      magnet hospitals in the USA, and means of two subscales were not significantly
      different from magnet hospital means. Hospitals could benefit from undertaking a
      similar practice environment baseline measure prior to applying for
      accreditation, thus enabling targeting of pre-identified service gaps and areas
      for improvement.

PMID- 18808538
TI  - Self-management in older patients with chronic illness.
AB  - Chronic illness causes the majority of disease burden and health costs in
      developed countries; however, this could be substantially reduced by optimal
      patient self-management. This study examined the levels of self-management in
      patients (n = 300) with chronic illness (chronic heart failure, chronic
      respiratory disease, Parkinson's disease and chronic schizophrenia) of moderate
      severity who had experienced an illness exacerbation in the last month. Patient's
      perceptions of self-efficacy in relation to their self-management and their sense
      of coherence were also assessed at baseline and 1 month later. No changes
      occurred in self-perceptions or self-management from baseline to follow-up.
      Patients at risk of poor self-management included people with low self-efficacy,
      poor sense of coherence, older age and a primary diagnosis of chronic
      schizophrenia. As self-efficacy is the only predictor known to be amenable to
      intervention, self-efficacy enhancing support should be promoted.

PMID- 18808539
TI  - Is there a place for ontological hermeneutics in mental-health nursing research?
      A review of a hermeneutic study.
AB  - A lot of research carried out within the context of mental-health nursing using
      qualitative data collection tools claims that it is hermeneutical, with usually
      just a short section describing the hermeneutical methodology as though it is a
      very broad philosophical approach. Criticisms of the latter approach more often
      than not concentrate on the level of the data collection tools without getting to
      grips with the underlying hermeneutical philosophy. This paper examines the
      difference between methodological and ontological hermeneutics and then gives an
      example of a piece of research using the latter approach. It is then argued that
      criticisms of the hermeneutical approach usually only concentrate on
      methodological hermeneutics with the consequence that they seriously misapply
      their criticisms if the research is using ontological hermeneutics.

PMID- 18808540
TI  - Developing professional autonomy in advanced nursing practice: the critical
      analysis of sociopolitical variables.
AB  - The conceptual tools prevailing in scientific literature can carry an unexamined
      ballast of implicit references to current sociopolitical debates that dominate
      their times. Professional autonomy is not only freedom for action but also
      freedom for thought. The paper aims to increase external validity by enhancing
      the awareness of uncontrollable variables and their very real impact on results.
      The method is a critical review of use of the concepts of vulnerability,
      participation and autonomy generally related to the public health discourse. It
      raises practical uncertainties regarding the overestimated prerequisite of
      'advanced' and 'evidence-based' practices when governing directives destined to
      be realized in social contexts fraught with unpredictability. This paper argues
      for the development of those skills necessary to analyse the influence of society
      dependent concepts on our daily practices and the impact institutions have on the
      construction of our values, ideologies and practices.

PMID- 18808541
TI  - Compliance of kidney transplant patients to the recommended lifestyle behaviours:
      single centre experience.
AB  - Successful management of kidney transplant patients requires lifelong therapeutic
      regimen. Lifestyle changes of the patients after transplantation is the key link
      between the process of transplantation and its outcome, which is why those
      patients are in great need for complying with their recommended lifestyle
      behaviours. The aim of the study was to identify compliance of kidney transplant
      patients to the recommended lifestyle behaviours. One hundred adult kidney
      transplant patients of 6 months duration and more participated in this study
      regardless of age or sex. A structured questionnaire was developed which included
      socio-demographic characteristics, the recommended lifestyle behaviours of the
      kidney transplant patients and the kidney transplant patient's health condition
      and his results from the laboratory tests. The time spent with each patient
      ranged between 45 and 60 min. About three or four patients were interviewed on
      each visit. The results found that patients have good compliance with
      immunosuppressive agents with partial degree to other lifestyle behaviours. The
      conclusion is that intensive assessment of patients before and after
      transplantation should be done to identify their needs which help to improve
      their compliance. The nurse must provide the kidney transplant patients with the
      necessary knowledge of the recommended lifestyle behaviours.

PMID- 18808542
TI  - Special Issue: Abstracts of the 34th British Society for Paediatric Dentistry
      Annual Scientific Meeting 2008, 16-19 September, Liverpool, UK. Editorial.

PMID- 18808544
TI  - UK National Clinical Guidelines in Paediatric Dentistry: stainless steel
      preformed crowns for primary molars.
AB  - This revised Clinical Guideline in Paediatric Dentistry replaces the previously
      published sixth guideline (Fayle SA. Int J Paediatr Dent 1999; 9: 311-314). The
      process of guideline production began in 1994, resulting in first publication in
      1997. Each guideline has been circulated widely for consultation to all UK
      consultants in paediatric dentistry, council members of the British Society of
      Paediatric Dentistry (BSPD), and to people of related specialities recognized to
      have expertise in the subject. The final version of this guideline is produced
      from a combination of this input and thorough review of the published literature.
      The intention is to encourage improvement in clinical practice and to stimulate
      research and clinical audit in areas where scientific evidence is inadequate.
      Evidence underlying recommendations is scored according to the SIGN
      classification and guidelines should be read in this context. Further details
      regarding the process of paediatric dentistry guideline production in the UK is
      described in the Int J Paediatr Dent 1997; 7: 267-268.

PMID- 18808545
TI  - UK National Clinical Guidelines in Paediatric Dentistry: diagnosis, prevention
      and management of dental erosion.
AB  - This revised Clinical Guideline in Paediatric Dentistry replaces the previously
      published ninth guideline (Shaw L, O'Sullivan E. Int J Paediatr Dent 2000; 10:
      356-365). The process of guideline production began in 1994, resulting in first
      publication in 1997. Each guideline has been circulated widely for consultation
      to all UK consultants in paediatric dentistry, council members of the British
      Society of Paediatric Dentistry (BSPD), and to people of related specialities
      recognized to have expertise in the subject. The final version of this guideline
      is produced from a combination of this input and thorough review of the published
      literature. In the case of the present guideline, an internationally recognized
      expert in the field was invited to be a co-author (AM). The intention is to
      encourage improvement in clinical practice and to stimulate research and clinical
      audit in areas where scientific evidence is inadequate. Evidence underlying
      recommendations is scored according to the SIGN classification and guidelines
      should be read in this context. Further details regarding the process of
      paediatric dentistry guideline production in the UK is described in the Int J
      Paediatr Dent 1997; 7: 267-268.

PMID- 18808546
TI  - British Society of Paediatric Dentistry: a policy document on consent and the use
      of physical intervention in the dental care of children.
AB  - This policy document was prepared by J Nunn, M Foster, S Master and S Greening on
      behalf of the British Society of Paediatric Dentistry (BSPD). Policy documents
      produced by the BSPD represent a majority view, based on a consideration of
      currently available evidence. They are produced to provide guidance with the
      intention that the policy be regularly reviewed and updated to take account of
      changing views and developments.

PMID- 18808558
TI  - Intensive care medicine and the Internal Medicine Journal: perfect bedfellows?

PMID- 18808559
TI  - On the case for an interview in medical student selection.

PMID- 18808560
TI  - Informed consent and medical ordeal: a qualitative study.
AB  - BACKGROUND: Informed consent is a mainstay of clinical practice, with both moral
      and legal forces. Material disclosure about extreme treatments, however, is
      unlikely to convey the full impact of the experience of treatment. Informed
      consent may be flawed under such circumstances. The aims of this study were to
      compare expressed satisfaction with pretreatment information to satisfaction
      after experiencing autologous stem cell transplantation for recurrent lymphoma.
      METHODS: A qualitative, narrative-based cohort study was conducted in a bone
      marrow transplant unit of a teaching hospital at Westmead Hospital, Sydney,
      Australia. The cohort consisted of 10 transplant recipients and 9 of their
      nominated lay carers. The outcome measure was satisfaction expressed in narrative
      interviews at the time of transplantation and 3 months later. We used discourse
      analytic techniques to examine the narratives. RESULTS: Both patients and carers
      expressed high satisfaction with the information given by individual clinicians
      and by speakers at a formal Information Day held before transplantation. At the
      first interview, neither patients nor carers commented much on the forthcoming
      ordeal of chemotherapy and bone marrow ablation, although all patients had
      undergone previous chemotherapy. At the second interview, the ordeal dominated
      the narratives and retrospective dissatisfaction with information was common.
      CONCLUSION: This study suggests that information about treatment theories and
      protocols can be satisfactorily communicated, but personal experience of
      suffering defies communication. This finding has serious implications for the
      practices involved in obtaining informed consent and for the very notion of
      informed consent.

PMID- 18808561
TI  - Treatment options and strategies for acute severe pulmonary embolism.
AB  - Pulmonary thromboembolism (PE) is the third most frequent cause of cardiovascular
      death after ischaemic heart disease and stroke. In fatal PE, 2/3 of patients die
      within first hour of presentation. There is a clinical impetus to rapidly
      recognize, risk-stratify and appropriately treat patients with acute severe PE.
      Current recommendations present conflicting classification systems, and there is
      often some confusion in the clinical evaluation and management of patients with
      acute severe PE. This review presents a series of real clinical cases, which
      illustrate the available treatment options, ranging from conservative therapy to
      thrombolysis through to percutaneous catheter fragmentation and open surgical
      embolectomy. We evaluate the evidence for the various strategies and propose an
      algorithm for clinicians with a focus on early risk stratification and timely
      referral. This is particularly relevant to regional and remote centres, as well
      as secondary and tertiary institutions.

PMID- 18808562
TI  - Kimura disease: review of the literature.
AB  - Kimura disease (KD) is a rare, chronic inflammatory disease of unknown cause and
      is characterized by painless s.c. swellings and lymphadenopathy commonly
      affecting the head and neck region. Much therapeutics has been used to treat KD,
      but is not satisfactory because of frequent relapse. Imatinib has been reported
      previously to be useful for treatment of hypereosinophilic syndrome and may work
      by selectively blocking protein-tyrosine kinases, such as platelet-derived growth
      factor receptor, and c-Kit. We carried out immunohistochemical examination of
      platelet-derived growth factor receptor-alpha and c-Kit in tissues from patients
      with KD. The results were positive and suggested that Imatinib might be an
      effective drug for the treatment of the disease. We have also briefly reviewed
      the epidemiology, aetiology, clinical manifestations, laboratory and pathological
      examinations, differential diagnoses, treatment and prognosis of KD in this
      manuscript.

PMID- 18808563
TI  - Persistent dystonia induced by fluoxetine.
AB  - Serotonin-selective re-uptake inhibitors are prescribed widely because they are
      regarded as having less severe side-effects compared with tricyclics and
      monoamine oxidase inhibitors. With this popularity, increasing attention has been
      drawn to their adverse effects. Development of extrapyramidal symptoms has been
      reported in some patients while taking fluoxetine, a commonly used serotonin
      selective re-uptake inhibitor. Here, we report a case of persistent dystonia,
      thought to be associated with short-term fluoxetine use, which required treatment
      with botulinum toxin type A.

PMID- 18808564
TI  - Periventricular nodular heterotopia and epilepsy.

PMID- 18808565
TI  - Erythema ab igne.

PMID- 18808567
TI  - Modafinil-induced psychosis.

PMID- 18808568
TI  - Pneumothorax and pleural empyema after acupuncture.

PMID- 18808569
TI  - 'Rainy day' stem cell storage for adult patients with acute myeloid leukaemia in
      first complete remission.

PMID- 18808570
TI  - Chorea in remote Aboriginal communities.

PMID- 18808573
TI  - Matching up to the airline industry.

PMID- 18808574
TI  - Nurses' responses to ethical dilemmas in nursing practice: meta-analysis.
AB  - AIM: This paper is a report of a study to explore nurses' responses to ethical
      dilemmas in daily nursing practice. BACKGROUND: Concern about nurses' ethical
      competence is growing. Most nurses perceived that there were barriers in their
      work environment to ethical practice, compromising their ability to perform
      ethically. Since most research focuses on contextual barriers to nurses' ethical
      practice, little is known about how nurses involve themselves in ethical decision
      making and action in daily care. METHOD: A meta-analysis of nurses' ethical
      behaviour was conducted using data from nine studies in four countries (n = 1592
      registered nurses). In all studies, the Ethical Behaviour Test was used to
      measure nurses' ethical responses, based on an adapted version of Kohlberg's
      theory of moral development. Data were analysed using random-intercept regression
      analysis. FINDINGS: All groups, except the expert group, displayed a uniform
      pattern of conventional ethical reasoning and practice. When nurses were faced
      with ethical dilemmas, they tended to use conventions as their predominant
      decision-guiding criteria rather than patients' personal needs and well-being.
      CONCLUSION: Conformist practice (following conventions rather than pursuing good
      for the patient) constitutes a major barrier for nurses to take the appropriate
      ethical actions, as creativity and critical reflection are absent. There is an
      urgent need to find ways to promote nurses' ethical development from conventional
      to postconventional ethical practice. More research is needed to strengthen
      existing empirical evidence.

PMID- 18808575
TI  - The experience of heavy menstrual bleeding: a systematic review and meta
      ethnography of qualitative studies.
AB  - AIM: This paper is a report of a systematic review and meta-ethnography of the
      experience of heavy menstrual bleeding. BACKGROUND: Heavy menstrual bleeding is
      common. Not all women seeking help have heavy menstrual bleeding as measured
      objectively and, conversely, some who do have this problem do not seek help. DATA
      SOURCES: Seven electronic databases were searched in 2004 and updated in 2008,
      and supplemented with hand-searching. METHOD: We identified four papers
      describing qualitative research among women with heavy menstrual bleeding. Key
      themes and concepts were extracted and synthesised using meta-ethnography, the
      key process of which is translation, identifying similar or contradictory
      findings in primary research. In the updated search three papers were identified.
      FINDINGS: Three papers were largely descriptive. These provided support for the
      fourth paper's conceptual framework of a lay model of heavy menstrual bleeding
      which shows little overlap with the traditional clinical definition. Details of
      physical, practical and emotional elements of this model were identified. A
      matrix of uncertainties were identified suggesting reasons why women may or may
      not seek medical help for heavy menstrual bleeding. Women and healthcare
      professionals may conspire to privilege blood loss over other symptoms and the
      disease model of heavy menstrual bleeding is little help to either. Two papers
      from the updated search were also largely descriptive. The third interpreted key
      elements of the lay model as relating to the need for concealment demanded by
      'menstrual etiquette'. CONCLUSION: A lay model of heavy menstrual bleeding is
      proposed, detailing key physical, social and emotional impacts that women find
      problematic.

PMID- 18808578
TI  - Making patients safer: nurses' responses to patient safety alerts.
AB  - AIM: This paper is a report of a study to determine whether action required by
      patient safety alerts was effectively taken. BACKGROUND: Over the last 10 years,
      there has been a growing awareness of the number of patients unintentionally
      harmed in the course of their treatment. Safety alerts are designed to reduce the
      incidence of adverse events by removing these predisposing factors. METHOD: A
      multi-method study was carried out in 20 acute, two mental health, four ambulance
      and 15 primary care provider organizations in the United Kingdom in 2006-2007
      using surveys, interviews with senior managers and front-line staff, collection
      of documentary evidence and equipment audit. The implementation of three safety
      alerts for nursing action is reported. FINDINGS: Most staff were aware of the
      dangers posed by gloves to staff with latex allergy, but only 20% were aware of
      the types of common equipment that posed a danger to sensitive patients. Almost
      40% of nurses were unable to give a correct acidity value to allow nasogastric
      feeding to commence. One alert, on needle-free intravascular connectors, was
      distributed in only a few organizations as the term used was unfamiliar at all
      levels of the organization. CONCLUSION: Healthcare providers have succeeded in
      setting up successful systems to disseminate alerts to middle management level,
      but there is evidence that implementation of recommendations by nurses is sub
      optimal.

PMID- 18808579
TI  - Reactions of primary caregivers of frail older people and people with cancer in
      the palliative phase living at home.
AB  - AIM: This paper is a report of a study conducted to (1) compare means of the
      single items and the dimensions of the Caregiver Reaction Assessment among
      caregivers of frail older people and caregivers of cancer patients in the
      palliative phase; (2) examine gender differences for the scoring parameters in
      the Caregiver Reaction Assessment within each group and (3) examine the
      demographic variables' association with the caregiver groups' scores for the
      dimensions of the Caregiver Reaction Assessment. BACKGROUND: Limited research has
      focused on the caregiver situation in the home-care setting among primary
      caregivers of frail older people, and caregivers of patients with cancer in the
      palliative phase. METHODS: A convenience sample of 224 caregivers of frail older
      people, and 85 caregivers of patients with cancer in the palliative phase was
      recruited between 2002 and 2005. We used the Caregiver Reaction Assessment to
      collect the data. RESULTS: The mean scores for the Caregiver Reaction Assessment
      dimensions showed statistically significant differences between the two groups of
      caregivers for the factors self-esteem, family support, finances and health. For
      caregivers of frail older people, we found statistically significant associations
      between several demographic variables and the Caregiver Reaction Assessment
      dimensions. For caregivers of patients with cancer in the palliative phase, age
      was the only demographic variable that was statistically significantly associated
      with the dimensions. CONCLUSION: Healthcare personnel should pay attention to how
      relatives experience their caregiver situation, and the Caregiver Reaction
      Assessment could be a valuable tool for gathering systematic data on this.

PMID- 18808580
TI  - Older people's experience of falls: understanding, interpretation and autonomy.
AB  - AIM: This paper is a report of a study to explore the experiences of older people
      who suffered a recent fall and identify possible factors that could contribute to
      service development. BACKGROUND: Falls in older people are prevalent and are
      associated with morbidity, hospitalization and mortality, personal costs to
      individuals and financial costs to health services. METHOD: A convenience sample
      of 27 older people (mean age 84 years; range 65-98) participated in semi
      structured taped interviews. Follow-up interviews during 2003-2004 were
      undertaken to detect changes over time. Data were collected about experience of
      the fall, use of services, health and well-being, activities of daily living,
      informal care, support networks and prevention. Thematic content analysis was
      undertaken. FINDINGS: Twenty-seven initial interviews and 18 follow-up interviews
      were conducted. The majority of people fell indoors (n = 23) and were alone (n =
      15). The majority of falls were repeat falls (n = 22) and five were a first-ever
      fall. People who reflected on their fall and sought to understand why and how it
      occurred developed strategies to prevent future falls, face their fear, maintain
      control and choice and continue with activities of daily living. Those who did
      not reflect on their fall and did not know why it occurred restricted their
      activities and environments and remained in fear of falling. CONCLUSION:
      Assisting people to reflect on their falls and to understand why they happened
      could help with preventing future falls, allay fear, boost confidence and aid
      rehabilitation relating to their activities of daily living.

PMID- 18808581
TI  - The immediate lived experience of the 2004 tsunami disaster by Swedish tourists.
AB  - AIM: This paper is a report of a study of the immediate lived experiences of
      victims and relatives of the 2004 tsunami disaster. BACKGROUND: Disasters serve
      to remind us of our frailty and vulnerability and raise existential questions.
      From the perspective of caring sciences, suffering is regarded as a natural
      source for change in patients' understanding of the world and the meaningfulness
      of their lives. METHOD: A phenomenological hermeneutic study was conducted, using
      in-depth interviews with a convenience sample of 19 informants in 2006-2007.
      Ricoeur's theory of interpretation served as a guiding principle for interpreting
      the interview texts. FINDINGS: The immediate lived experiences of the tsunami
      survivors and their relatives revealed a comprehensive picture, described as
      different acts of the drama. These acts were: 'experiencing the very core of
      existence', 'a changed understanding of life' and 'the power of communion'.
      Confronting our frailty and vulnerability makes us more authentic to ourselves,
      to our relatives and to life itself. The first step towards progression involves
      an act where the suffering is seen and validated by another person. Reshaping the
      suffering together with the family adds a valuable dimension to life.
      Availability and presence by the family opened up for communion. CONCLUSION: The
      immediate lived experiences of the tsunami disaster from an existential and
      ontological perspective constitute an important aspect of understanding the whole
      phenomenon. Concepts such as communion, understanding life and progression of
      suffering can help us construct an image of this previously unresearched
      dimension.

PMID- 18808582
TI  - Benchmarking nurse staffing levels: the development of a nationwide feedback
      tool.
AB  - AIM: This paper is a report of a study to develop a methodology that corrects
      nurse staffing for nursing care intensity in a way that allows nationwide
      benchmarking of nurse staffing data. BACKGROUND: Although nurse workload
      measurement systems are recognized to be informative in nurse staffing decisions,
      they are rarely used. When these systems are used, however, it is only possible
      to compare units within hospitals, because currently available instruments are
      not standardized for comparisons beyond hospital boundaries. The Belgian Nursing
      Minimum Dataset (B-NMDS) contains uniformly measured data about the intensity of
      nursing care and nurse staffing levels for all hospitals in Belgium. METHOD: We
      conducted a retrospective multilevel analysis of the B-NMDS for the year 2003.
      The sample included 690,258 inpatient days for 298,691 patients, recorded from
      1637 acute care nursing units in 115 hospitals. We corrected the number of
      nursing staff by using different covariates available in the B-NMDS: intensity of
      nursing care, type of day (week vs. weekend), service type (general vs.
      intensive) and hospital type (academic vs. general). FINDINGS: The multilevel
      approach allowed us to explain about 70% of the variability in the number of
      nursing staff per nursing unit using hospital type (P = 0.0053); intensity of
      nursing care (P < 0.0001) and service type (P < 0.0001) as the only covariates.
      CONCLUSION: The feedback tool we developed can inform nurse managers and
      policymakers about nursing intensity-adjusted nurse staffing levels according to
      different benchmarks. Our study demonstrates that investing in large nursing
      datasets is appropriate for the international nursing community.

PMID- 18808583
TI  - Nurses' perceptions of preoperative teaching for ambulatory surgical patients.
AB  - AIM: This paper is a report of a study to examine nurses' perceptions of the
      importance of providing preoperative information to ambulatory surgical patients,
      and factors that might influence their provision of such teaching. BACKGROUND:
      Ambulatory surgery is now widespread and creates a challenge for nurses to
      provide preoperative teaching in the limited contact time they have with
      patients. Although nurses act as key educators in patient teaching, little is
      known about their perceptions of the importance of preoperative teaching, or
      about current practice in the provision of such teaching for ambulatory surgical
      patients. METHODS: A self-administered questionnaire including demographics and
      the Preoperative Teaching Questionnaire was completed by 91 of the 169 eligible
      nurses (response rate 53.8%) working in day-surgery units, operating theatres or
      outpatient clinics providing ambulatory surgery services in two public hospitals
      in Hong Kong in 2005. RESULTS: A discrepancy between nurses' perceptions and
      practice in relation to the provision of preoperative information was found.
      Limited teaching aids, tight operation schedules and language barriers affected
      the delivery of preoperative information to ambulatory surgical patients.
      CONCLUSION: The results highlight the importance of reviewing current
      preoperative teaching methods and improving the effectiveness of such teaching to
      enhance the quality of care for ambulatory surgical patients.

PMID- 18808584
TI  - The transition to parenthood: what does it mean for fathers?
AB  - AIM: This paper is a report of a study to explore the needs of first-time fathers
      in relation to the care, support and education provided by healthcare
      professionals during the antenatal period, particularly in relation to preparing
      them for the transition to fatherhood. BACKGROUND: Pregnancy and transition to
      parenthood are major developmental periods within families throughout the world.
      Previous research suggests that fathers in many different countries feel
      unprepared for parenthood. METHODS: Purposive sampling was used to recruit 20
      partners of primiparous women from two healthcare provider organizations in South
      West England between December 2005 and July 2006. Recruitment took place at about
      28 weeks gestation. Semi-structured interviews were undertaken at home in the
      last trimester of pregnancy and 3-4 months postpartum. Content analysis of the
      interview data was undertaken. FINDINGS: Several common themes emerged from both
      the ante- and postnatal data, including lack of support mechanisms, involvement
      in antenatal provision and the need for more information given in the antenatal
      period on parenting, baby care and relationships. CONCLUSIONS: Adequately
      preparing new fathers for parenthood in advance of the birth of their baby is
      important, and healthcare professionals can contribute to this by involving and
      supporting new fathers. Further study is needed to explore the role of fathers in
      antenatal education and the types of interventions that are effective in
      improving their early experiences of parenthood. The study needs to be repeated
      with fathers from black and ethnic minority groups.

PMID- 18808585
TI  - Adherence: a concept analysis.
AB  - AIM: This paper is a report of an analysis of the concept of adherence.
      BACKGROUND: The transition in terminology from compliance to adherence, and more
      recently to concordance, requires re-clarification of 'adherence' as a concept in
      nursing practice. Differences exist in the use of the term adherence and how or
      if it differs from compliance or concordance. DATA SOURCES: Using the Medical
      Subject Headings terms adherence, non-adherence and treatment refusal, the
      Cumulative Index to Nursing and Allied Health Literature, Medline, PsychINFO and
      Cochrane library databases were searched for publications between 1970 and 2007.
      Method. The evolutionary analytic method was used to identify and explore
      transitions in the concept of adherence over time and across healthcare
      disciplines. A representative sample of papers was identified from the
      disciplines of nursing, medicine, psychology and pharmacy. RESULTS: We identified
      114 papers: 27 from nursing, 39 from psychology, 33 from general medicine and 15
      from pharmacology sources. The final sample included eight from pharmacy and 15
      from mental health, medicine and nursing. We found no distinct differentiation
      between adherence and compliance. The surrogate terms serving as manifestations
      of adherence are concordance, agreement, cooperation and partnership. The most
      common definition found was as follows: 'Adherence can be defined as the extent
      to which patients follow the instructions they are given for prescribed
      treatments'. No definition of adherence exists that reflects a patient-centred
      approach, the dynamic nature of adherence behaviour and the power imbalance
      implied by these terms. CONCLUSION: This concept analysis of adherence is a
      preliminary step towards broadening nurses' appreciation of the complexity of
      patient adherence behaviour.

PMID- 18808586
TI  - Resisting readers and resistant texts.

PMID- 18808589
TI  - Maternal role development following childbirth among Australian women.
AB  - AIM: This paper is a report on the examination of demographic, birthing and
      social correlates of maternal role development in childbearing women. BACKGROUND:
      Successful adaptation to the maternal role provides a mother with confidence and
      satisfaction in her ability to nurture and care for her infant. Despite the
      importance of this developmental process for maternal well-being, little
      attention has been given to social and demographic predictors of positive role
      development in recent years. METHODS: A prospective study was undertaken at three
      publicly-funded metropolitan antenatal clinics in Queensland, Australia between
      March and November 2003. A total of 605 women completed a survey at 36 weeks
      gestation and 12 weeks postpartum, with a response rate of 78% (n = 473). A self
      report questionnaire was used to collect data about personal and birth variables,
      domestic violence, social support and maternal role development. FINDINGS: The
      majority of women (81%) were of White ethnic background, modal age was 30-45
      years (40%, n = 189) and 66 percent (n = 312) were in paid employment. Bivariate
      analysis identified age, marital status, length of relationship and social
      support to be statistically significantly associated with maternal role
      development. Optimal scaling showed social support to be the most important
      factor in maternal role development. CONCLUSION: Maternal role development
      following childbirth is complex and can be adversely affected by older maternal
      age, married status, inadequate social support and short partner relationships. A
      deeper understanding of this process is needed if healthcare professionals are to
      assist mothers in making a smooth transition to motherhood.

PMID- 18808590
TI  - Self-reported competence of home nursing staff in Finland.
AB  - AIM: This paper is a report of a study to investigate the self-reported
      competence of home nursing staff and whether this is associated with their
      education, job descriptions, access to help and support and with factors in their
      psychosocial work environment, such as opportunities for personal growth and
      development at work. BACKGROUND: Home nursing staff face increasing demands on
      their competence. Advances in information technology and working methods have
      increased the need for education. Thus, information on the factors associated
      with the competence of home nursing staff help us to support them in a way that
      improves the quality of care. METHOD: The data were gathered via a questionnaire
      completed in 2003 by the home nursing staff of 24 municipalities in different
      regions of Finland. A total of 2366 home care staff (response rate 63%), of whom
      790 were home nursing staff (response rate 65%), were sent questionnaires.
      Univariate and multivariate logistic regression were used as main statistical
      methods. FINDINGS: The best predictors for self-reported competence of home
      nursing staff were their reading scientific or professional journals,
      opportunities for skill development, decision-making latitude and work demands.
      CONCLUSION: Simple and practical ways for updating the competence of home nursing
      staff should be created. These staff are a very important source of information
      for home care clients. Supporting the knowledge of home nursing staff is also an
      efficient way of keeping clients and their informal caregivers informed about
      care guidelines, health and social services and social benefits.

PMID- 18808591
TI  - Education for new role development: the Community Matron in England.
AB  - AIM: This paper is a report of an evaluation of the English national pilot
      education programme preparing Community Matrons to fulfil their role. BACKGROUND:
      Investment in community services has been important in introducing new ways of
      working in the United Kingdom National Health Service, particularly for patients
      with complex long-term conditions. Development of the Community Matron role in
      England is an exemplar in the creation of modern nursing careers that are fit for
      purpose. METHOD: A mixed methods approach to data collection was adopted. This
      included documentary analysis of a range of sources used in the development and
      evaluation of the programme. In addition, during 2006, a self-administered
      questionnaire was sent to all Community Matrons undertaking the programme (n =
      70), with a response rate of 67% (n = 47). Individual telephone interviews were
      conducted with 17 students and six mentors. A focus group was also undertaken
      with the education programme Development Team (n = 5). Quantitative data were
      analysed using SPSS and qualitative data analysed using content and thematic
      analyses. FINDINGS: The majority of students (n = 25) believed that the programme
      had met their expectations and had helped them to achieve the functions of the
      Community Matron role as defined in national competence statements. However, 17
      students experienced difficulties in the level of organisational readiness to
      support them in their role, including, for example, lack of facilitation of their
      work-based learning. CONCLUSION: In spite of the successful programme design,
      there is a need for organisations to develop their infrastructure to support new
      roles as well as offering protected time to learn in practice.

PMID- 18808592
TI  - Diversity, attrition and transition into nursing.
AB  - AIM: This paper is a report of a study to explore the relationship between
      selected diversity variables (sex, country of birth, ethnicity, age, educational
      qualifications, and additionally visa status, application route, absence rates),
      and nursing students' progression and attrition. BACKGROUND: Debates on levels,
      forms and causation of nursing student attrition have been professional, academic
      and political concerns for some time on an international level. However, a more
      systematic approach to studying the topic is needed. We lack commonly
      operationalized national and international data on the relationship between
      attrition and diversity variables, and their implications for cost, social
      justice and demographic representativeness in nursing. METHODS: A longitudinal
      cohort design was used. Data were collected from 2003 to 2005 from routinely
      collected data in student records. RESULTS: Males had lower odds of completing
      the programme than females, as did younger students. Compared with United Kingdom
      born students, those born in Ireland, Zimbabwe, or other English-speaking
      countries were more likely to complete the programme. Students born overseas in
      non-English-speaking countries did not differ statistically significantly from
      United Kingdom-born students. Those at all qualification levels had similar odds
      of completion, except students already qualified at degree level, who were less
      likely to complete. CONCLUSION: Further national and international research is
      needed to understand better the causal variables underpinning differential
      attrition rates, with particular regard to understanding how different groups may
      experience the relationship between education and their broader circumstances and
      between the theoretical and the clinical elements of nurse education itself.

PMID- 18808593
TI  - Development of an internet-based intervention for parents of infants.
AB  - AIM: This paper reports on a study to describe the development of an internet
      based intervention for parents with infants and to compare the participants and
      hospitals at baseline. BACKGROUND: There is a need for interventions to support
      parenting and for more research into the use of information technology as an
      intervention strategy. The design and development of healthcare interventions is
      a complex task, but these are rarely discussed in research reports. METHODS: A
      quasi-experimental study was conducted. The data (N = 1300 families) were
      collected using a structured questionnaire at the hospital or no later than 1
      week after discharge during the winter of 2006. The results were used to develop
      the intervention and to compare the participants at baseline. Statistically
      significant differences were determined by chi-squared or Fisher's exact tests
      for percentages and one-way anova for means. The internal consistency
      relialibility of the scales was analysed using Cronbach's alpha coefficients.
      FINDINGS: Participants in the intervention (n = 469 mothers, n = 307 fathers) and
      control (n = 394 mothers, n = 218 fathers) hospitals were comparable in respect
      of parent and infant attributes. There were statistically significant differences
      between the hospitals in fathers' overnight stays and their access to social
      support from professionals on the maternity ward. Exclusive breastfeeding was
      more common in the intervention hospital. More support for infants' cues and
      behaviour, and day-rhythm and sleep were needed in the intervention hospital.
      CONCLUSION: More research is needed to gain a clearer understanding of the effect
      size of the differences for a reliable evaluation of the effectiveness of the
      proposed intervention.

PMID- 18808594
TI  - Investigating the determinants of health-related quality of life among childhood
      cancer survivors.
AB  - AIM: This paper is a report of a study to survey early childhood cancer
      survivors' perceived health-related quality of life and its determinants and to
      estimate the reliability of known psychometric scales used in the measurement of
      these determinants. BACKGROUND: Young adult survivors of childhood cancer are
      considered to be a high-risk, vulnerable population for experiencing medical and
      psychosocial sequelae from their treatment that can adversely affect their health
      related quality of life. Achieving an adequate level of health-related quality of
      life among childhood cancer survivors has been identified as a significant
      outcome in measuring the success of cancer treatment for these survivors
      throughout the world. METHOD: An on-line survey approach was used, and data were
      collected from December 2005 to May 2006 in the United States of America.
      Specific determinants measured were physical health status, perceived sense of
      hopefulness, self-esteem, social support and affect. The internal consistency of
      the instruments to measure these constructs among early survivors of childhood
      cancer was evaluated. FINDINGS: Early survivors of childhood cancer had a lower
      level of health-related quality of life, perceived self-esteem, physical health
      status and social support when compared with previously reported findings among
      samples of adolescents in active treatment for cancer, healthy same-age peers and
      other samples of childhood cancer survivors. CONCLUSION: Investigations using web
      based approaches to measure determinants of health-related quality of life among
      young adult survivors of childhood cancer have the potential to include
      international samples of childhood cancer survivors.

PMID- 18808595
TI  - Celluloid angels: a research study of nurses in feature films 1900-2007.
AB  - AIM: This paper is a report of a study examining the influence on how nursing and
      nurses are portrayed in feature films made between 1900 and 2007, with a nurse as
      their main or a principle character and a story-line related specifically to
      nursing. BACKGROUND: Nurses and the nursing profession are frequently portrayed
      negatively or stereotypically in the media, with nurses often being portrayed as
      feminine and caring but not as leaders or professionals capable of autonomous
      practice. METHODS: A mixed method approach was used to examine feature films made
      in the Western world. Over 36,000 feature film synopses were reviewed (via
      CINAHL, ProQuest and relevant movie-specific literature) for the keywords
      'nurse'/'nursing'. Identified films were analysed quantitatively to determine
      their country of production, genre, plot(s) and other relevant data, and
      qualitatively to identify the emergence of themes related to the image of
      nurses/nursing in films. FINDINGS: For the period from 1900 to 2007, 280 relevant
      feature films were identified. Most films were made in the United States of
      America or United Kingdom, although in recent years films have been increasingly
      produced in other countries. Early films portrayed nurses as self-sacrificial
      heroines, sex objects and romantics. More recent films increasingly portray them
      as strong and self-confident, professionals. CONCLUSION: Nurse-related films
      offer a unique insight into the image of nurses and how they have been portrayed.
      Nurses need to be aware of the impact the film industry has on how nurses and
      nursing are perceived and represented in feature films.

PMID- 18808596
TI  - Complexity Prediction Instrument to detect 'complex cases' in respiratory wards:
      instrument development.
AB  - AIM: This paper is a report of a study to test the hypothesis that the Spanish
      version of the Complexity Prediction Instrument is a reliable and valid measure
      of complexity of patients with respiratory disease and to identify the frequency
      of positive indicators of potential complexity. BACKGROUND: Respiratory patients
      are often disabled and severely ill, with co-morbid physical conditions and
      associated psychosocial problems and need complex nursing care. METHOD: Trained
      nurses assessed 299 consecutive adult patients admitted to a respiratory service
      in Spain from May 2003 until June 2004 with the new, Spanish version of the
      instrument. Criterion-related validity was tested by studying its ability to
      predict complexity of care in terms of: severity of illness, scored using the
      Cumulative Illness Rating Scale; length of hospital stay; 'multiple
      consultations' during admission; and 'multiple specialists' after discharge.
      FINDINGS: The hypothesis was supported: patients rating above the standard cut
      off point on the Complexity Prediction Instrument scored statistically
      significantly higher on most of the measures of care complexity studied. Linear
      regression models showed that the tool was associated with 'length of hospital
      stay', and predicted both 'multiple consultations' and 'multiple specialists',
      after controlling for potential confounders. The proportion of 'probable complex
      cases' was 59.5%. Five positive indicators of potential complexity had a
      frequency higher than 50%. CONCLUSION: The Complexity Prediction Instrument is
      reliable and valid in a new clinical area, respiratory disease. It may be used by
      nurses for the early prediction of complexity of care. International comparisons
      may be facilitated with this new Spanish version.

PMID- 18808597
TI  - Effectiveness of a falls-and-fracture nurse coordinator to reduce falls: a
      randomized, controlled trial of at-risk older adults.
AB  - OBJECTIVES: To assess the effectiveness of a community-based falls-and-fracture
      nurse coordinator and multifactorial intervention in reducing falls in older
      people. DESIGN: Randomized, controlled trial. SETTING: Screening for previous
      falls in family practice followed by community-based intervention. PARTICIPANTS:
      Three hundred twelve community-living people aged 75 and older who had fallen in
      the previous year. INTERVENTION: Home-based nurse assessment of falls-and
      fracture risk factors and home hazards, referral to appropriate community
      interventions, and strength and balance exercise program. Control group received
      usual care and social visits. MEASUREMENTS: Primary outcome was rate of falls
      over 12 months. Secondary outcomes were muscle strength and balance, falls
      efficacy, activities of daily living, self-reported physical activity level, and
      quality of life (Medical Outcomes Study 36-item Short Form Questionnaire).
      RESULTS: Of the 3,434 older adults screened for falls, 312 (9%) from 19 family
      practices were enrolled and randomized. The average age was 81+/-5, and 69%
      (215/312) were women. The incidence rate ratio for falls for the intervention
      group compared with the control group was 0.96 (95% confidence interval=0.70
      1.34). There were no significant differences in secondary outcomes between the
      two groups. CONCLUSION: This nurse-led intervention was not effective in reducing
      falls in older people who had fallen previously. Implementation and adherence to
      the fall-prevention measures was dependent on referral to other health
      professionals working in their usual clinical practice. This may have limited the
      effectiveness of the interventions.

PMID- 18808599
TI  - Renal net acid excretion capacity is comparable in prepubescence, adolescence,
      and young adulthood but falls with aging.
AB  - OBJECTIVES: To evaluate whether renal net acid excretion capacity (NAEC) varies
      across different age groups and, specifically, whether it falls in elderly
      people. DESIGN: Cross-sectional observational study. SETTING: Community-based.
      PARTICIPANTS: Young participants were from the DOrtmund Nutritional and
      Anthropometric Longitudinally Designed Study, Dortmund, Germany; elderly
      participants were from Gothenburg, Sweden. MEASUREMENTS: Twenty-four-hour urine
      pH, net acid excretion (NAE), urinary phosphorus, total nitrogen excretion, and
      anthropometric data were measured in healthy elderly people (aged 55-75; n=85),
      young adults (aged 18-22; n=117), adolescents (aged 13-14; n=112), and
      prepubescent children (aged 6-7; n=217). NAEC was determined as 24-hour NAE
      adjusted for urine pH using the residual method. RESULTS: In elderly participants
      24-hour urinary pH (5.9+/-0.53) was lower (P<.05) and NAE (60+/-27 mEq/d) higher
      (P<.05) than in the three other groups. In a regression model adjusted for age,
      sex, and body surface area, NAEC showed a clear decrease with age, with highest
      values in prepubescents and lowest in elderly participants. However, NAEC
      remained significantly lower only in elderly participants (P<.001) after the
      inclusion of total nitrogen excretion, a protein intake index, which was included
      because protein intake is known to modulate renal function. NAEC was
      approximately 8 mEq/d lower in healthy elderly participants than in young adults.
      CONCLUSION: The capacity to excrete net endogenous acid does not vary markedly
      from childhood to young adulthood but falls significantly with age, implying that
      elderly people may require higher daily alkalizing mineral intake to compensate
      for renal function losses.

PMID- 18808598
TI  - At the tipping point: predicting severe mobility difficulty in vulnerable older
      women.
AB  - OBJECTIVES: To identify clinical measures that aid detection of impending severe
      mobility difficulty in older women. DESIGN: Cross-sectional and longitudinal
      cohort study. SETTING: Urban community in Baltimore, Maryland. PARTICIPANTS: One
      thousand two community-dwelling, moderate to severely disabled women aged 65 and
      older in the Women's Health and Aging Study I. MEASUREMENTS: Self-report and
      performance measures representing six domains necessary for mobility: central and
      peripheral nervous systems, muscles, bones and joints, perception, and energy.
      Severe mobility difficulty was defined as usual gait of 0.5 m/s or less, any
      reported difficulty walking across a small room, or dependence on a walking aid
      during a 4-m walking test. RESULTS: Four hundred sixty-seven out of 984 (47%) had
      severe mobility difficulty at baseline, and 104/474 (22%) developed it within 12
      months. Baseline mobility difficulty was correlated with poor vision, knee pain,
      feelings of helplessness, inability to stand with feet side by side for 10
      seconds, difficulty keeping balance while dressing or walking, inability to rise
      from a chair five times, and cognitive impairment. Of these, knee pain (odds
      ratio (OR)=1.74, 95% confidence interval (CI)=1.05-2.89), helplessness (OR=1.87,
      95% CI=1.10-3.24), poor vision (OR=2.03, 95% CI=1.06-3.89), inability to rise
      from a chair five times (OR=2.50, 95% CI=1.15-5.41), and cognitive impairment
      (OR=4.75, 95% CI=1.67-13.48) predicted incident severe mobility difficulty within
      12 months, independent of age. CONCLUSION: Five simple measures may aid
      identification of disabled older women at high risk of severe mobility
      difficulty. Further studies should determine generalizability to men and higher
      functioning individuals.

PMID- 18808600
TI  - Europe-wide survey of teaching in geriatric medicine.
AB  - By 2050, the European population of 720 million will include 187 million (one
      quarter) octogenarians. Although living longer is a true privilege, care for the
      graying population suffering from chronic and disabling diseases will raise
      enormous challenges to healthcare systems and geriatric education. Are European
      countries ready to cope with these challenges? An extensive 2006 survey of
      geriatric education in thirty-one of 33 European countries testifies that
      geriatrics is a recognized medical specialty in 16 countries and a subspecialty
      in nine of them. Six European countries have an established chair of geriatric
      medicine in each of their medical schools. Undergraduate teaching activities are
      organized in 25 of the surveyed countries and postgraduate teaching in 22
      countries under the leadership of geriatricians (n=16) or general internists
      (n=6). A comparison with data collected in the 1990s shows important progresses:
      the number of established chairs increased by 45%, the undergraduate and
      postgraduate teaching activities increased respectively by 23% and 19%. However,
      these changes are very heterogeneously organized from country to country and
      within each country. In most European countries, there remains a huge need for
      reinforcing and harmonizing geriatric teaching activities to prepare the next
      generation of medical doctors to address the projected increase in chronic and
      disabled older patients. Several different innovative strategies are proposed.

PMID- 18808601
TI  - Multifactorial fall-prevention strategies: time to retreat or advance.

PMID- 18808602
TI  - Randomized clinical trial results for donepezil in Alzheimer's disease: is the
      treatment glass half full or half empty?

PMID- 18808603
TI  - As we are now: nursing home resident as educator.

PMID- 18808604
TI  - Community-dwelling elderly fallers in Japan are older, more disabled, and more
      depressed than nonfallers.

PMID- 18808605
TI  - Subjective sleep disturbances were closely associated with comprehensive
      geriatric functions in dose-responsive manner in the community-dwelling elderly
      people in Japan.

PMID- 18808606
TI  - Serum calcium and prediction of cognitive decline in old age.

PMID- 18808607
TI  - Anemia and response to epoetin alfa: the cause of anemia matters!

PMID- 18808608
TI  - Five times sit to stand test is a predictor of recurrent falls in healthy
      community-living subjects aged 65 and older.

PMID- 18808609
TI  - Economic burden of informal caregivers for elderly Chinese in Hong Kong.

PMID- 18808610
TI  - Clinical profile of patients with symptomatic glycyrrhizin-induced hypokalemia.

PMID- 18808611
TI  - The geriatric emergency department.

PMID- 18808612
TI  - Who receives house calls?

PMID- 18808613
TI  - Improvement in obesity and glucose tolerance in elderly people after lifestyle
      changes 1 year after an oral glucose tolerance test in a rural area in Lao
      People's Democratic Republic.

PMID- 18808614
TI  - An attempt to characterize factors that affect participation in minimal-risk
      research of older adults: what can we learn from published research findings?

PMID- 18808615
TI  - Taken by the wind: frail elder wind advisories?

PMID- 18808616
TI  - Stereotactic radiosurgery for trigeminal neuralgia in a 109-year-old woman.

PMID- 18808618
TI  - The practice and research of complementary and alternative medicine in nursing.

PMID- 18808619
TI  - A systematic review of the efficacy of non-pharmacological treatments for
      depression on glycaemic control in type 2 diabetics.
AB  - AIMS AND OBJECTIVES: This paper reported a systematic review of three randomised
      controlled clinical trials evaluating the efficacy of non-pharmacological
      treatment of depression on glycaemic control in individuals with type 2 diabetes.
      BACKGROUND: Depression is associated with poor adherence to self-care regimen in
      individuals with diabetes. A significant relationship between depression and poor
      glycaemic control has also been suggested. Hence, the management of depression
      becomes an important aspect of diabetes care. DESIGN: Systematic review. METHODS:
      Cochrane library, Pubmed, MEDLINE, EBM review, ProQuest Medical Bundle and SCOPUS
      databases were searched using the following medical subject headings or key words
      - depression, mood disorder, depressive symptoms, diabetes mellitus, glycaemic
      control, glycated haemoglobin, glucose, psychological therapy, psychotherapy, non
      pharmacological therapy and cognitive behaviour therapy. The publication date was
      limited from 1996-2007. Studies were selected if they used a randomised
      controlled trial design, were written in English, used non-pharmacological
      treatments for treating depression, included individuals with type 2 diabetes
      mellitus as participants and included depressive symptoms and glycaemic control
      (determined by haemoglobin A(1)C) as outcomes. RESULTS: Non-pharmacological
      treatments of depression reduce depressive symptoms in diabetic patients.
      However, cognitive behaviour therapy did not improve glycaemic control. The
      treatment effect sizes for glycaemic control in the two collaborative-care
      programmes were also small. CONCLUSIONS: The available evidence indicated that
      non-pharmacological treatment of depression had limited effect on glycaemic
      control in individuals with type 2 diabetes. RELEVANCE TO CLINICAL PRACTICE: The
      depression-focused interventions might not achieve optimal diabetes-related
      outcomes. The beneficial effect of psychological treatment for glycaemic control
      may be strengthened by employing treatments tailored to each individual's
      diabetes self-care needs in addition to depression management.

PMID- 18808620
TI  - Systematic review and meta-analysis of the efficacy of tuina for cervical
      spondylosis.
AB  - AIMS AND OBJECTIVES: This study performed a meta-analysis of seven parallel-group
      comparison studies evaluating the efficacy of tuina in treating cervical
      spondylosis. BACKGROUND: Tuina is a form of Chinese manipulative therapy. It has
      been used as a modality for the treatment of symptoms associated with such a
      musculoskeletal condition as cervical spondylosis. However, evidence regarding
      the efficacy of tuina for cervical spondylosis has yet to be determined. DESIGN:
      Systematic review. METHODS: Cochrane library, Pubmed, MEDLINE, EBM review,
      ProQuest Medical Bundle and SCOPUS databases were searched using the following
      medical subject headings or key words: tuina, tuinaology, manual medicine,
      massotherapy, cervical spondylopathy, cervical spondylosis and cervical
      vertebrae. Chinese research papers were searched through the Chinese electronic
      periodical services and Wangfane database. The publication date was limited from
      1996-2007. Studies were selected if they were written in English or Chinese, used
      tuina as a stand-alone modality, used a parallel-group comparison design and
      explicated raw data regarding symptoms relief. Two independent reviewers reviewed
      the selected studies based on the evidence rating system of the US Preventive
      Services Task Force. Studies with an evidence rating of II-2 fair or above were
      included in this review. RESULTS: The direction of the effect size for the
      improvement of blood flow velocity of vertebral artery and basilar artery was not
      consistent across studies. Moreover, the pooled effect size was negligible. No
      evidence supported that tuina could improve headache and vertigo. A small effect
      of tuina on the viscosity of blood and plasma was found. CONCLUSION: Based on the
      results of this systematic review, a definitive conclusion regarding the effects
      of tuina on cervical spondylosis remains to be determined. RELEVANCE TO CLINICAL
      PRACTICE: The efficacy of tuina is not supported by parallel-group comparison
      studies.

PMID- 18808621
TI  - A study on the efficacy of body-mind-spirit group therapy for patients with
      breast cancer.
AB  - AIMS AND OBJECTIVES: This study aims to understand the effects of culturally
      enriched body-mind-spirit group therapy on anxiety, depression and holistic well
      being among women with breast cancer and to examine patients' views on what
      aspects of group therapy worked to enhance their health. DESIGN: The study was
      designed using multiple methods, which consisted of a randomised controlled trial
      and a focus group interview. METHODS: A total of 16 subjects in the control group
      received the standard care of a physician's treatment at the outpatient
      department. In addition to standard care, 12 subjects in the experimental group
      received 10 sessions of weekly body-mind-spirit group therapy for 180 minutes
      each. This therapy integrates concepts and practices of traditional Chinese
      medicine and Western medicine (e.g. positive psychology and forgiveness therapy).
      The subjects in the experimental group were invited to participate in a focus
      group interview regarding their perceptions of the change mechanisms that
      occurred in group therapy. RESULTS: The results of analysis of covariance
      indicated that after a two-month trial, there was a similarity between the
      experimental and control groups in reducing the scores of Beck depression
      inventory and increasing the scores of body-mind-spirit well-being. However,
      subjects in the experimental group had a better reduction of the scores of state
      anxiety inventory than subjects in the control group. The qualitative analysis
      yielded eight domains: (i) imparting of information, (ii) interpersonal learning,
      (iii) catharsis, (iv) universality, (v) group cohesiveness, (vi) altruism, (vii)
      instillation of hope and (viii) existential factors. These domains illustrate how
      the therapeutic effects of group therapy worked to reduce patients' anxiety.
      CONCLUSION: The culturally sensitive body-mind-spirit group therapy reduced
      anxiety among outpatients with breast cancer. RELEVANCE TO CLINICAL PRACTICE: The
      involvement of mental health nurses in providing group therapy for cancer
      patients could enhance the quality of care in psycho-ontological nursing.

PMID- 18808622
TI  - Evaluation of services of the integrative health clinic in Hong Kong.
AB  - AIMS: (i) To provide a profile of the clients who have used the Integrative
      Health Clinic's services, (ii) to determine the clients' extent of satisfaction
      with the services received and (iii) to assess whether integrative therapies
      can/should be recommended to other clinics. BACKGROUND: Based on the integration
      of various health paradigms and the use of health promotion strategies, our
      Integrative Health Clinic in Hong Kong provides a range of different therapies
      for integrated symptom management. The integrative therapies are derived from
      conventional, complementary and alternative medicine. Design. Postal survey,
      followed by routine data analysis. METHOD: Hong Kong Chinese clients attending a
      residential community health clinic were surveyed about health status and
      satisfaction towards the services received. RESULTS: A total of 489 clients
      (30.8% were male and 69.2% female) were registered with the clinic during the
      study period. The mean age (SD) was 47.8 (15.4) years. The customer satisfaction
      survey found that traditional Chinese medicine consultation was the most
      frequently used modality of the Integrative Health Clinic, followed by pain
      management. Out of the 489 clients, those who attended the Integrative Health
      Clinic only once in the study period for an annual health assessment and those
      who died during the period were excluded from the survey, giving a total of 276
      eligible clients. Out of the 276 clients, 52.5% (128) responded to the survey
      that asked them to evaluate their satisfaction with the services received at the
      clinic and the performance of the clinic's practitioners who interacted with
      them. For practitioner performance, the percentage of respondents who gave a
      rating of satisfaction was found to range between 86.3-64.3%, while the
      percentage of respondents who gave a rating of dissatisfaction ranged from 13.7
      35.7%. Overall, the survey found that most aspects of the Integrative Health
      Clinic's services were rated as satisfactory. CONCLUSION: The overwhelming
      satisfaction of clients with the services they received at the Integrative Health
      Clinic suggests that this integrative health services model could be considered
      for adoption in other clinics in Hong Kong and perhaps the region. RELEVANCE TO
      CLINICAL PRACTICE: It is necessary to review the use of integrative therapies so
      as to provide more data for the evaluation of this increasingly popular modality
      of health services.

PMID- 18808623
TI  - Exploration of the use of complementary and alternative medicine among Turkish
      children.
AB  - AIMS AND OBJECTIVES: This study explored the use of complementary and alternative
      medicine among Turkish children and the factors affecting their use. BACKGROUND:
      Estimates of CAM use in children range from 9-70%. Most studies of CAM use in
      Turkey have focussed on adults. No study has been reported on the use of CAM in
      Turkish children without specific diagnosed illnesses. DESIGN: Survey. METHODS: A
      questionnaire was completed with the parents of 600 children attending the
      paediatric clinics of three hospitals in western Turkey. Information about CAM
      use and factors affecting its use among children and their parents was collected
      by interview using a structured questionnaire. RESULTS: A majority of parents
      (57%) used CAM therapies for their child, with herbal therapy used most
      frequently (77%). The use rate of CAM was 49% for children with respiratory
      system problems and 25% for children with digestive system problems. Fifty-nine
      per cent of parents stated that they used CAM to comfort their children and 25%
      to support prescribed medical therapy. The most frequent recommendation to use
      CAM came from one or more family members (55%). Parents who were university
      graduates, lived in the city, had one child and had used this type of therapy
      themselves were more inclined to use CAM for their children. There was no
      reported use of therapies such as chiropractic, naturopathy or acupuncture.
      CONCLUSION: There is frequent use of CAM among Turkish children and it is viewed
      as additional to treatment prescribed by physicians. RELEVANCE TO CLINICAL
      PRACTICE: Most often, parents do not discuss CAM use with doctors or nurses.
      Health professionals should routinely ask parents about CAM use and discuss the
      reasons and expected outcomes of use. Only through such discussion can health
      professionals understand and respect parents' use of CAM for their children and
      guide them in their choices.

PMID- 18808624
TI  - A traditional Chinese herbal medicine used to treat dysmenorrhoea among Taiwanese
      women.
AB  - AIM: The purposes of this study were twofold, firstly to ascertain the relative
      effectiveness of the alternative drug, Si-Wu-Tang (SWT), for dysmenorrhoea
      treatment and secondly to compare two different timings for consumption of SWT in
      terms of menstrual pain. DESIGN: A two-group time series experimental design.
      METHODS: A total of 49 participants were alternately assigned into two study
      groups. The experimental group was provided with 15 g of SWT daily for seven
      consecutive days, subsequent to the cessation of menstrual bleeding, for two
      consecutive menstrual cycles and the comparison group was provided with a similar
      intervention as soon as menstrual bleeding was noted. The degree of menstrual
      pain was recorded daily using a visual analogue scale and the duration of pain
      was also recorded during menstrual bleeding for five consecutive menstrual
      cycles. RESULTS: The results indicated that the decrease in menstrual pain levels
      and the duration of pain between the experimental group and the comparison group
      was not significant. However, the decrease in menstrual pain over the five
      menstrual cycles within the experimental group (from 2.07 to 1.42; 2.71 to 1.21;
      p < 0.05) and within the comparison group (from 1.94 to 1.23; 2.66 to 1.68; p <
      0.05) were significant. CONCLUSIONS: The SWT formula has been continuously
      standardised for effective use as part of menstrual health and can be integrated
      as an alternative therapy within Western medicine. RELEVANCE TO CLINICAL
      PRACTICE: This study provides information for health care professionals not only
      about the general principles of traditional Chinese medicine, but also about the
      selection and consumption of an appropriate SWT formula among Asian women with
      dysmenorrhoea. Moreover, nurses should build up a partnership with their clients
      of Asian origins based on the use of an alternative therapy using different
      assessment criteria that are related to healing and recovery based on bodily
      constitution balance.

PMID- 18808625
TI  - Pain experiences, control beliefs and coping strategies in Chinese elders with
      osteoarthritis.
AB  - AIM: To explore pain experiences, pain control beliefs and pain coping strategies
      among elders with osteoarthritis in Taiwan. BACKGROUND: Osteoarthritis, a
      degenerative disease that commonly affects older people, is manifested by pain
      and disability. Despite the increasing number of older people, few studies have
      explored their chronic pain experiences, pain beliefs and pain coping strategies.
      DESIGN: Survey. METHODS: Participants (n = 205) were recruited by convenience
      sampling from three outpatient clinics at a medical centre in northern Taiwan.
      Data were collected by questionnaire on pain sites, pain intensity, pain
      interference with activity, pain control beliefs, pain coping strategies,
      depressive tendency and demographic variables. Scores of worst pain intensity
      were used to divide participants into three groups: mild, moderate and severe
      pain. RESULTS: Participants' average number of pain sites was 2.9 (SD 2.2). Most
      participants (70%) suffered moderate to severe worst pain. Participants perceived
      average pain control beliefs (mean 1.7, SD 0.7). Most used pharmacological coping
      strategies about half of the time (mean 1.8, SD 0.7) and non-pharmacological
      coping strategies about one-quarter of the time (mean 1.0, SD 0.5). Scores on
      satisfaction with living situation, depressive tendency, pain intensity, pain
      interference, pain control beliefs and frequency of using pharmacological coping
      strategies differed significantly among the three pain groups. Results of
      regression analysis showed that the intensity of average pain, pain interference
      with walking, pain interference with sleeping and pain control beliefs
      significantly predicted intensity of worst pain, explaining 54% of the variance
      in intensity of worst pain. CONCLUSION: This study highlights the importance of
      dealing with pain in this population. RELEVANCE TO CLINICAL PRACTICE: Since
      health care providers play an important role in helping elders to manage pain,
      the authors recommend training physicians and nurses to regularly assess pain and
      to provide current knowledge about pain assessment and management strategies for
      elders with osteoarthritis.

PMID- 18808626
TI  - A systematic review of honey uses and its potential value within oncology care.
AB  - AIM: To synthesise the evidence regarding honey's role in health care and to
      identify whether this evidence applies more specifically to cancer care. DESIGN:
      Systematic review. METHODS: The inclusion and exclusion criteria were agreed by
      two reviewers and a keyword strategy was developed. EMBASE, CINAHL, AMED,
      MEDLINE, COCHRANE and PUBMED databases were screened to identify suitable
      articles. The citation list from each included study was also screened for
      potentially suitable papers. The key findings from each study were entered onto a
      data extraction sheet. RESULTS: In total, 43 studies were included in the
      systematic review, which included studies in relation to wounds (n = 19), burns
      (n = 11), skin (n = 3), cancer (n = 5) and others (n = 5). In addition, a
      systematic review regarding honey use in wound care was also included. While the
      majority of studies noted the efficacy of honey in clinical use, five studies
      found honey to be equally as effective as the comparator and three found honey to
      be less effective than the comparator treatment. Other research did not
      illustrate any significant difference between standard treatment regimes vs.
      honey treatment. Studies were generally poor in quality because of small sample
      sizes, lack of randomisation and absence of blinding. CONCLUSIONS: Honey was
      found to be a suitable alternative for wound healing, burns and various skin
      conditions and to potentially have a role within cancer care. RELEVANCE TO
      CLINICAL PRACTICE: In the cancer setting, honey may be used for radiation-induced
      mucositis, radiotherapy-induced skin reactions, hand and foot skin reactions in
      chemotherapy patients and for oral cavity and external surgical wounds.

PMID- 18808627
TI  - The outcome of tactile touch on oxytocin in intensive care patients: a randomised
      controlled trial.
AB  - AIM: To explore the effects of five-day tactile touch intervention on oxytocin in
      intensive care patients. The hypotheses were that tactile touch increases the
      levels of oxytocin after intervention and over a six-day period. BACKGROUND:
      Research on both humans and animals shows a correlation between touch and
      increased levels of oxytocin which inspired us to measure the levels of oxytocin
      in arterial blood to obtain information about the physiological effect of tactile
      touch. DESIGN: Randomised controlled trial. METHOD: Forty-four patients from two
      general intensive care units, were randomly assigned to either tactile touch (n =
      21) or standard treatment--an hour of rest (n = 23). Arterial blood was drawn for
      measurement of oxytocin, before and after both treatments. RESULTS: No
      significant mean changes in oxytocin levels were found from day 1 to day 6 in the
      intervention group (mean -3.0 pM, SD 16.8). In the control group, there was a
      significant (p = 0.01) decrease in oxytocin levels from day 1 to day 6, mean 26.4
      pM (SD 74.1). There were no significant differences in changes between day 1 and
      day 6 when comparing the intervention group and control group, mean 23.4 pM (95%
      CI -20.2-67.0). CONCLUSION: Our hypothesis that tactile touch increases the
      levels of oxytocin in patients at intensive care units was not confirmed. An
      interesting observation was the decrease levels of oxytocin over the six-day
      period in the control group, which was not observed in the intervention group.
      RELEVANCE TO CLINICAL PRACTICE: Tactile touch seemed to reduce the activity of
      the sympathetic nervous system. Further and larger studies are needed in
      intensive care units to confirm/evaluate tactile touch as a complementary caring
      act for critically ill patients.

PMID- 18808628
TI  - Physical fitness of older adults in senior activity centres after 24-week silver
      yoga exercises.
AB  - AIMS AND OBJECTIVES: Promoting physical fitness of young-older adults is
      essential in reducing healthcare expenditures which would occur in the future for
      those with chronic health problems. The silver yoga exercise programme was
      developed to accommodate the reduced body flexibility experienced by many older
      adults and was critically reviewed by experts and pilot-tested with community
      dwelling older adults. This study aimed to test older adults' physical fitness
      after a 24-week silver yoga exercise programme and to examine whether the
      programme could be further shortened to fit senior activity centres' programme
      designs. DESIGN: A quasi-experimental, pre-post tests design was used: baseline,
      at 12-week and at 24-week periods. METHODS: Convenience samples of 204 subjects
      were recruited from eight senior activity centres and 176 subjects completed the
      study. Subjects were randomly assigned into three groups based on the centres:
      (1) Experiment I: complete silver yoga with stretching and meditation, (2)
      Experiment II: shortened silver yoga without the guided-imagery meditation and
      (3) Wait-list control. The interventions were conducted three times per week for
      24 weeks. Physical fitness indicators included body compositions, cardiovascular
      respiratory functions, physical functions and the range of motion. RESULTS: At
      the end of the 24-week period, the physical fitness of subjects in Experiments I
      and II had significantly improved whether or not guided-imagery meditation was
      used and all had better physical fitness than subjects in the control group (all
      p < 0.05). CONCLUSIONS: The physical fitness of older adults in both the 70
      minute complete silver yoga group and the 55-minute shortened silver yoga group
      had significantly improved after the interventions. It was recommended that the
      silver yoga programme be shortened by eliminating the guided-imagery meditation.
      RELEVANCE TO CLINICAL PRACTICE: The shortened silver yoga exercise programme is
      recommended to be incorporated as an activity programme in community-settings to
      promote the physical fitness of older adults.

PMID- 18808629
TI  - Meet the real elders: reminiscence links past and present.
AB  - AIMS AND OBJECTIVES: This study was designed to develop an understanding of the
      process of reminiscence and the roles played by nurses in fostering reminiscence
      as a therapeutic intervention. BACKGROUND: Reminiscence therapy has been
      considered an effective nursing strategy for improving quality of life and
      preventing depression in nursing home settings. Until recently, however, there
      has been little attention to understanding the dynamics of reminiscence therapy
      and the interaction between a nurse and an older client during reminiscence.
      DESIGN: A qualitative research design employing participant observation and
      content analysis of recorded reminiscence therapy sessions was used in this
      study. METHODS: Participant observation was used to explore the process of
      individual reminiscence therapy and identify nursing roles in the process
      generated. Ten nursing home residents participated and data were collected over
      two months through interviews and observation. Content analysis was used to
      identify emerging themes. RESULTS: Reminiscence occurred in four stages: entree,
      immersion, withdrawal and closure. Stimuli related to participants' past lives
      were helpful for initiating reminiscence. Nursing roles in each stage were
      identified. CONCLUSION: A tentative model of the process of reminiscence was
      derived from study findings. Further study is needed to validate the model in
      nursing practice with older clients. RELEVANCE TO CLINICAL PRACTICE: Reminiscence
      could be initiated by nursing staff at anytime during care of residents.
      Information about the reminiscence process and related nursing roles may be
      helpful in understanding and assisting adaptation in nursing home residents.

PMID- 18808630
TI  - Randomised controlled trial of music on state anxiety and physiological indices
      in patients undergoing root canal treatment.
AB  - OBJECTIVES: The purpose of this randomised investigator-blind controlled trial is
      to examine the effects of music on the state anxiety and physiological indices
      among patients undergoing root canal treatment. DESIGN: Randomised controlled
      trial. METHODS: Purposive sampling was used to recruit 44 adult subjects. The
      subjects were randomly assigned to the treatment and the control group. There
      were 22 subjects in each group. Subjects in the music group listened to selected
      sedative music using headphones throughout the root canal treatment procedure.
      The control group subjects worn headphones but without the music. Using a
      repeated measures design with a single pretest and five posttests, the subjects'
      heart rate, blood pressure and finger temperature were measured before the study
      and every 10 minutes until the end of the root canal treatment procedure. Anxiety
      was measured before the study and at the end of the treatment procedure. RESULTS:
      The results revealed that there were no significant differences between the two
      groups for baseline data and procedure-related characteristics, except for
      gender. However, the subjects in the music group showed a significant increase in
      finger temperature and a decrease in anxiety score over time compared with the
      control group. The effect size for state anxiety and finger temperature was 0.34
      and 0.14 respectively. RELEVANCE TO CLINICAL PRACTICE: The findings provide
      evidence for nurses and dentists that the use of soothing music for anxiety
      reduction in patients undergoing root canal treatment procedures is supported by
      research findings.

PMID- 18808631
TI  - Commentary on Bardy J, Slevin NJ, Mais KL & Molassiotis A (2008) A systematic
      review of honey uses and its potential value within oncology care. Journal of
      Clinical Nursing 17, 2604-2623.

PMID- 18808632
TI  - Commentary on Spilsbury K, Petherick E, Cullum N, Nelson A, Nixon J & Mason S
      (2008) The role and potential contribution of clinical research nurses to
      clinical trials. Journal of Clinical Nursing 17, 549-557.

PMID- 18808635
TI  - Random acts of guidance: personal reflections on professional generosity.

PMID- 18808636
TI  - A literature review of principles, policies and practice in extended nursing
      roles relating to UK intensive care settings.
AB  - AIMS: To provide an overview of the literature relating to the principles, policy
      and practice of extended nursing roles in UK intensive care settings to date; to
      review and critically assess evidence of impact, outcomes and effect on practice
      and provide suggestions for future research. BACKGROUND: It is known that career
      development opportunities, new technologies, patient needs, as well as the
      reduction in junior doctors' hours, are driving the development of new roles for
      nurses. Policy initiatives aim to expand nursing roles to support professional
      substitution. In adult, neonatal and paediatric intensive care, specialist
      trained nurses and designated advanced nursing practitioners are increasingly
      taking on extended practice of clinical tasks previously undertaken by medical
      staff. As yet there are no statutory regulations on the perceived scope and
      definition of the role of extended and advanced roles. DESIGN: Systematic review.
      METHODS: Search of electronic databases and selection of policy and peer-reviewed
      reports and reviews of extended nursing roles or advanced nursing practitioners
      in UK intensive care settings. RESULTS: Chronological review shows policy
      development proceeding in a relatively ad hoc way. There is limited information
      available about how extensively or effectively extended nursing roles are being
      implemented in intensive care settings in the UK, particularly in adult and
      paediatric intensive care. To test local initiative findings for reliability and
      generalisability, a more robust evidence base is required. CONCLUSIONS: More data
      are needed on definition and outcomes of extended nursing roles in intensive care
      and care process measures should be developed to better inform implementation of
      nurse role development in the UK. RELEVANCE TO CLINICAL PRACTICE: The review of
      policy and research evidence in this paper may better inform clinicians working
      in adult, neonatal or paediatric intensive care, as they continue to be
      challenged by expansion and development of their role. It may also help to form a
      basis and evaluation for future research into extended and advanced nursing roles
      in intensive care settings.

PMID- 18808637
TI  - Stressors in the ICU: a comparison of patients' and nurses' perceptions.
AB  - AIMS AND OBJECTIVES: The aim of the study was to compare the stressors as
      perceived by patients in an intensive care unit (ICU) against those of nurses on
      the basis of their perceptions of patients' stressors. BACKGROUND: Getting
      admitted to an ICU is viewed as a stressful event by patients. However, numerous
      studies have indicated that nurses do not always accurately perceive the
      stressors of their clients. Therefore, it is important for nurses to know what
      seems most stressful from the patients' perspective so that appropriate nursing
      measures can be directed towards minimising such stressors. DESIGN: Survey.
      METHODS: As a convenience sample, 60 patients and 54 critical care nurses were
      recruited. The Intensive Care Unit Stressor Questionnaire (Chinese) (ICU-CSQ) was
      used to collect the perceptions of stressors by the patients. Nurses were also
      asked to rate the items in the said questionnaire according to how they believe
      patients would rate them. RESULTS: In every comparison, nurses evaluated the
      items to be significantly more stressful than patients did. Overall perceived
      stress levels of nurses were also significantly higher than those of their
      patients (z = -8.78, p < 0.001). CONCLUSIONS: Nurses tended to rate the items as
      more stressful than did the patients, perhaps over-emphasising the stressful
      nature of the ICU. The findings also highlight the importance of cultural beliefs
      on the perceived stress levels among the Chinese population. RELEVANCE TO
      CLINICAL PRACTICE: Findings in this study have strong implications in clinical
      practice, especially in a critical care setting. Nurses must attempt to identify
      and endeavour to cope with the situations that patients listed as most stressful.
      Moreover, attention must be drawn towards measures aimed at relieving the stress
      of patients by taking into account their cultural values so that culture-specific
      interventions for reducing their stress can be established.

PMID- 18808638
TI  - Experiences of living with a malignant fungating wound: a qualitative study.
AB  - AIMS AND OBJECTIVES: The purpose of this study was to explore the experience of
      cancer patients living with a malignant fungating wounds. BACKGROUND: Malignant
      fungating wounds are caused by cancerous cells invading skin tissue. These wounds
      can then bleed, become malodorous and painful causing physical and psychological
      distress. However, little is know about how individuals experience these lesions.
      DESIGN: Qualitative. METHODS: Ten in-depth interviews were conducted with
      patients in one medical teaching centre in Taiwan. Data were subject to a
      thematic analysis informed by elements of grounded theory. RESULTS: Five key
      themes demonstrated an emerging model that offers an insight into how patients
      experience their wound. Firstly, 'Declining physical well-being' refers to the
      initial impact of the wound, this is linked to two further themes; 'Wound related
      stigma' and the 'Need for expert help'. Another theme; 'Strategies in wound
      management' describes the initial, ineffective attempts by participants to manage
      their wound and the impact of professional help around wound management. This was
      linked to a fifth theme; 'Living positively with the wound' that reflected how
      patients adjusted to the presence of the wound -- significantly influenced by the
      wound care they received. CONCLUSION: This study contributes to the understanding
      we have of how patients experience living with such wounds. It sets out the clear
      need for early use of wound specialists as part of the multi-disciplinary
      oncology team. RELEVANCE TO CLINICAL PRACTICE: The results of this study provides
      a description of patient experiences that can help to guide nursing practice as
      well as an understanding of what a malignant fungating wound means to cancer
      patients and how it influences their lives.

PMID- 18808639
TI  - Patients' expectations of the maintenance of their dignity.
AB  - AIMS AND OBJECTIVES: To explore patients' views regarding the factors that
      contribute to the maintenance of their dignity while in hospital, together with
      their perceptions of whether or not these were realised. BACKGROUND: It has long
      been recognised that a consideration of patients' dignity in the hospital setting
      is of paramount importance and its maintenance can contribute to the 'emotional
      comfort' that may assist recovery. There have been several attempts to define
      dignity as a theoretical concept, but few studies of the factors that contribute
      to its maintenance from the patients' perspective. DESIGN: A phenomenological
      hermeneutic approach was used. METHOD: Interviews were conducted with 102
      patients in three hospitals in the UK over 18 months. The intention was to
      interpret what was being said and also the underlying meaning of how patients
      considered that their dignity was compromised. RESULTS: The findings revealed
      that although many patients were satisfied with the maintenance of their dignity
      while in hospital, a significant number were not. Six key themes that contribute
      to the preservation of their dignity were identified -- privacy; confidentiality;
      communication and the need for information; choice, control and involvement in
      care; respect and decency and forms of address. Patients provided details of
      their expectations with respect to these factors. CONCLUSIONS: Patients,
      irrespective of their situation and degree of health have their own expectations
      in relation to their dignity. These need to be assessed and matched by relevant
      nursing activities to assist recovery. RELEVANCE TO CLINICAL PRACTICE: Nurses
      have an important role in meeting patients' expectations of how they would like
      their dignity to be maintained. The identification of the most important factors
      that contribute to this from patients' perspective will help develop dignified
      nursing practice.

PMID- 18808640
TI  - Nurses' experience in clinical encounters with children experiencing abuse and
      their parents.
AB  - AIM AND OBJECTIVES: The aim of this study was to identify nurse's experiences in
      the clinical care of children experiencing abuse. The objective was to assess how
      nurses remain professional especially when the suspected perpetrator is a parent.
      BACKGROUND: The diagnosis of child abuse is a difficult one, yet essential
      because of the high morbidity and significant mortality rates. Young children may
      be unable to give a clear history; parents may be unwilling to be truthful, and
      the signs and symptoms of abuse are often not conclusive. A contributing factor
      to the challenges of providing nursing care to children in a context of abuse is
      the lack of education in this field. Nurses working in the care of paediatric
      patients may not be familiar with situations in which they cannot rely on
      histories provided by parents. DESIGN: A qualitative study. METHODS:
      Investigators used a qualitative design with a critical incident technique.
      Eleven nurses who cared for abused children and their parents at a tertiary care
      children's hospital were interviewed. RESULTS: We highlighted three areas in the
      analysis of the interviews: Feelings of ambivalence, nurses' professionalism and
      the nurses' care strategies. Participants expressed difficulties in maintaining a
      professional role in clinical encounters with the parents. The nurses were
      unhappy in their conflicting roles of both policing (a judging function) and
      nursing (a caring function). CONCLUSIONS: The nurses expressed that they had
      devised strategies to remain professional in the clinical encounter with abused
      children and their parents. To remain professional, education, counselling and
      experience was essential. RELEVANCE TO CLINICAL PRACTICE: By identifying nurses'
      experiences in clinical encounters with children experiencing abuse and their
      parents, nurses can assess what kind of specific interventions should be used to
      improve the caring situation.

PMID- 18808641
TI  - Use of drug therapy in children with attention deficit hyperactivity disorder
      (ADHD): maternal views and experiences.
AB  - AIMS AND OBJECTIVES: The aim of this paper is to explore maternal views and
      experiences of stimulant pharmacotherapy in children with attention deficit
      hyperactivity disorder (ADHD). BACKGROUND: The very nature of ADHD means that it
      exists in a climate of scepticism and doubt. However, parents must make decisions
      about how to treat their children affected by ADHD. Of the treatments available,
      the use of stimulant therapy is the most controversial. DESIGN: Qualitative.
      METHOD: Snowball sampling was used to recruit mothers (n = 11) of children with
      ADHD and a narrative-based qualitative methodology was used. RESULTS: Decisions
      around the use of stimulant medication for children with ADHD were difficult for
      these mothers. Detailed findings are presented under the themes of: Ambivalence
      and confusion: everybody would be down on me like a ton of bricks; Influence of
      the media: so much bad publicity; Deciding against medication: you're changing
      their whole personality; and, Deciding for medication: he's just been wonderful.
      CONCLUSIONS: While these mothers revealed that they were discriminating in
      selecting information to guide their decision-making, many of their friends and
      family were influenced solely by media reports. Mothers experienced misgivings
      from family and friends who were sceptical about the need for medication and the
      implications and ethics of administering stimulant medication to children.
      RELEVANCE TO CLINICAL PRACTICE: Nurses and healthcare professionals have an
      important role in providing accurate and current information for parents and
      families and should be aware of the pressures parents are under when making
      decisions about treatments for their children with ADHD.

PMID- 18808642
TI  - Coping mechanisms of parents of children recently diagnosed with autism in
      Taiwan: a qualitative study.
AB  - OBJECTIVE: To understand the coping mechanisms of Taiwanese parents whose
      children have recently been diagnosed with autism. BACKGROUND: When a child is
      diagnosed with autism, the family's life changes. Parents of a child with autism
      have been shown to cope with problem- or emotion-focused coping strategies.
      However, it is not known how parents in Taiwan adapt and cope with the stresses
      of taking care of an autistic child, especially in the early period after
      learning their child's diagnosis and while waiting for free national day care
      arrangements at hospital. DESIGN: A descriptive qualitative design was used, with
      in-depth interviews. METHODS: Parents of children diagnosed with autism (n = 17)
      were recruited from a children's psychiatric outpatient clinic at a medical
      centre in northern Taiwan. The parents were still waiting for free national day
      care arrangements at hospital. Data were collected through individual, tape
      recorded interviews and observations, and transcripts were analysed by content
      analysis for emerging themes and concepts. RESULTS: The study sample of parents
      of children with autism described nine main coping mechanisms that fell into
      three core categories: adjusting to self-change, developing treatments for the
      autistic child and seeking support. CONCLUSIONS: The results of this study could
      be used by clinicians to help parents of autistic children become aware of
      whether or not they are using healthy coping mechanisms, and to suggest concrete
      and healthy coping strategies, particularly in the period after the diagnosis is
      confirmed and they are waiting for free national day care arrangements at
      hospital. RELEVANCE TO CLINICAL PRACTICE: Clinicians in child psychiatry are
      encouraged to become part of the social support network for parents of autistic
      children, thus helping them adjust to the long journey of caring for their
      children.

PMID- 18808643
TI  - Parental experience of family resources in single-parent families having a child
      with cancer.
AB  - AIM: The purpose of this study was to explore the essence of family experiences
      in terms of family resources and how these assist a single-parent caring for a
      child with cancer. BACKGROUND: When families face stresses caused by cancer, they
      need to readjust their roles, interactive patterns and relationships, both inside
      and outside the family. During the adaptation process, family resources may
      assist recovery from stress and a return to equilibrium. Most research has
      emphasised the support resources available to two-parent families during the
      treatment process. There is a lack of information on the experiences of single
      parent families and their available resources together with the functions and
      roles played by family resources during the adjustment process. DESIGN:
      Qualitative. RESULTS: Five major themes were identified: (i) facing the disease
      with courage; (ii) hope kindled by professionals; (iii) constructing parental
      role ability; (iv) assisting the children to live with the illness; and (v)
      family flexibility. CONCLUSION: The results of the current study demonstrate that
      single-parent families with a child suffering from cancer employ family resources
      to assist family adjustment and to maintain family function/equilibrium. These
      results explain the dynamic interactions between the multiple levels of resources
      available to the family. RELEVANCE TO CLINICAL PRACTICE: The study results
      provide evidence-based information that identifies the nature of family resources
      in single-parent families and describes how these resources can be applied to
      assist the families.

PMID- 18808644
TI  - Shifting supervision: implications for safe administration of medication by
      nursing students.
AB  - BACKGROUND: Medication errors made unintentionally by nurses continue to be a
      major concern in hospitals, medical centres and aged care facilities throughout
      Australia. While there is a plethora of literature available, which has
      identified factors that contribute to nurses making errors, few studies have
      reported on factors that may contribute to errors made by nursing students.
      DESIGN: A grounded theory approach. METHODS: In-depth interviews with final-year
      undergraduate nursing students (n = 28) to explore their experiences of
      administering medication. Constant comparative analysis was used to identify
      categories from the data. RESULTS: The central category was identified as
      'shifting levels of supervision'. This describes the process of supervision
      students received when administering medication. Four levels were identified:
      'being with', 'being over', 'being near' and 'being absent'. The findings suggest
      that nursing students do not always receive the level of supervision that is
      legally required. Less than satisfactory levels of supervision were identified by
      participants as leading to medication errors or near misses. CONCLUSION: Apart
      from 'Being with', the levels of supervision described by participants have major
      implications for the safe administration of medication by nursing students and
      represent the actual or potential cause of error. RELEVANCE TO CLINICAL PRACTICE:
      The potential for medication errors pose a major safety issue. Healthcare
      services have a responsibility to protect patient safety. Appropriate supervision
      of nursing students when administering education therefore requires urgent
      attention to ensure best practice is executed.

PMID- 18808645
TI  - The status of training and education in information and computer technology of
      Australian nurses: a national survey.
AB  - AIMS AND OBJECTIVES: A study was undertaken of the current knowledge and future
      training requirements of nurses in information and computer technology to inform
      policy to meet national goals for health. BACKGROUND: The role of the modern
      clinical nurse is intertwined with information and computer technology and
      adoption of such technology forms an important component of national strategies
      in health. The majority of nurses are expected to use information and computer
      technology during their work; however, the full extent of their knowledge and
      experience is unclear. DESIGN: Self-administered postal survey. METHODS: A 78
      item questionnaire was distributed to 10,000 Australian Nursing Federation
      members to identify the nurses' use of information and computer technology.
      Eighteen items related to nurses' training and education in information and
      computer technology. RESULTS: Response rate was 44%. Computers were used by 86.3%
      of respondents as part of their work-related activities. Between 4-17% of nurses
      had received training in each of 11 generic computer skills and software
      applications during their preregistration/pre-enrolment and between 12-30% as
      continuing professional education. Nurses who had received training believed that
      it was adequate to meet the needs of their job and was given at an appropriate
      time. Almost half of the respondents indicated that they required more training
      to better meet the information and computer technology requirements of their jobs
      and a quarter believed that their level of computer literacy was restricting
      their career development. Nurses considered that the vast majority of employers
      did not encourage information and computer technology training and, for those for
      whom training was available, workload was the major barrier to uptake. Nurses
      favoured introduction of a national competency standard in information and
      computer technology. CONCLUSIONS: For the considerable benefits of information
      and computer technology to be incorporated fully into the health system,
      employers must pay more attention to the training and education of nurses who are
      the largest users of that technology. RELEVANCE TO CLINICAL PRACTICE: Knowledge
      of the training and education needs of clinical nurses with respect to
      information and computer technology will provide a platform for the development
      of appropriate policies by government and by employers.

PMID- 18808646
TI  - The effectiveness of an educational programme for nursing students on developing
      competence in the provision of spiritual care.
AB  - AIM: To determine the effects of a course for nursing students on developing
      competence in spiritual care and the factors that might influence the effects.
      BACKGROUND: Studies suggest that role preparation in nursing for spiritual care
      is poor. For the assessment of competence, few or no explicit competency
      framework or assessment tools seemed to be used. DESIGN: Quasi-experimental
      crossover design (pre-post-test). METHOD: The subjects were students from
      Christian nursing schools in the Netherlands (n = 97). The intervention consisted
      of a course in spiritual care. Competencies were measured with an assessment
      tool, the Spiritual Care Competence Scale. Data were analysed by t-test
      procedures (paired-samples t-test). At T(1) vignettes were added to assess the
      quality of the students' own analyses. These data were analysed by a Mann-Whitney
      test. Regression analyses were performed on the influence of student
      characteristics on the subscales of the assessment tool. RESULTS: Ninety-seven
      students participated in this study. Analysis showed statistically significant
      changes in scores on three subscales of the Spiritual Care Competence Scale
      between groups (T(1)) and over time for the whole cohort of students on all
      subscales (T(2)). Clinical placement showed as a negative predictor for three
      subscales of the Spiritual Care Competence Scale. Experience in spiritual care
      and a holistic vision of nursing both showed as positive predictors on certain
      competencies. A statistically significant difference was observed between groups
      in the student analysis of a vignette with explicit spiritual content.
      CONCLUSIONS: The outcomes raise questions about the content of education in
      spiritual care, the measurement of competencies and the factors that influence
      competency development. RELEVANCE TO CLINICAL PRACTICE: The results provide nurse
      educators with insight into the effects of education in spiritual care on
      students' competencies and help them consider a systematic place for spiritual
      care within the nursing curriculum.

PMID- 18808647
TI  - Effects of an empowerment-based education program for public health nurses in
      Taiwan.
AB  - AIM AND OBJECTIVES: The aim of this study was to examine the effects of an
      empowerment-based education program (EBEP) on employee empowerment, job
      satisfaction, job productivity and innovative behaviours for public health nurses
      (PHN) in Taiwan. BACKGROUND: Empowerment is an important consideration among
      nurses trying to function in ever-changing health care and education settings.
      Several studies focused on the trend of public health nursing revealed that PHN
      have experienced a severe feeling of powerlessness. Developing empowerment
      strategies through organisations may be a means of helping employees recognise
      powerlessness in difficult situations and take appropriate action. DESIGN: Quasi
      experimental design. METHODS: PHN in two health bureaus in Taiwan were assigned
      into an empowerment group (n = 29) and a control group (n = 32). Twenty-four
      hours of the EBEP lasted four weeks included four empowerment classes and four
      group workshops following each curriculum for PHN to apply principles of
      empowerment in their work environment. Data were collected at baseline and four
      weeks after the intervention. Analysis of covariance (ancova) was used to examine
      the intervention effect. RESULTS: The experimental group reported significantly
      higher psychological empowerment [F (1,47) = 5.09, MSE = 3.25, p = 0.001, eta(2)
      = 0.18] and competence [F (1,47) = 3.96, MSE = 28.78, p = 0.05, eta(2) = 0.22]
      and impact [F (1,47) = 4.98, MSE = 44.79, p = 0.002, eta(2) = 0.20] subscales,
      job productivity [F (1,47) = 4.88, MSE = 5.18, p = 0.002, eta(2) = 0.19] and
      innovative behaviours [F (1,47) = 5.09, MSE = 3.25, p = 0.001, eta(2) = 0.24]
      than the control group after the EBEP. CONCLUSION: The EBEP had significant
      effect on psychological empowerment and subscales of competence and impact,
      innovative behaviour and job productivity but no effect on organisational
      empowerment and job satisfaction for PHN. RELEVANCE TO CLINICAL PRACTICE: Our
      findings suggest public health administration could design empowerment-based
      education to improve employee empowerment and job productivity for PHN.
      Furthermore, using multiple components to design empowerment education should be
      considered in further studies.

PMID- 18808648
TI  - Reliability of nurse assessment of malnutrition risk in hospital patients.

PMID- 18808649
TI  - Commentary on Secomb J (2008) A systematic review of peer teaching and learning
      in clinical education. Journal of Clinical Nursing17, 703-716.

PMID- 18808651
TI  - Commentary on Paley J (2008) Spirituality and secularization: nursing and the
      sociology of religion. Journal of Clinical Nursing17, 175-186.

PMID- 18808653
TI  - Bilateral severe carotid artery steno-occlusive disease: when is simultaneous
      treatment of both carotid arteries justified?

PMID- 18808655
TI  - Diffusion tensor tractography-based analysis of the pyramidal tract in patients
      with amyotrophic lateral sclerosis.
AB  - BACKGROUND AND PURPOSE: We attempted to measure DTI parameters of the brainstem
      pyramidal tract using two approaches, ie, simple ROI and tract-specific analyses.
      Results obtained for healthy subjects and ALS patients were compared. METHODS:
      DTI was performed using a single shot SE-EPI with 25 noncollinear diffusion
      gradient directions (b= 1000 second/mm(2)) and with no diffusion gradient on a
      3.0-T MR system in 10 ALS patients and in 8 age- and sex-matched normal controls.
      To delineate the brainstem pyramidal tract, tractography was performed using two
      ROIs, ie, a seed ROI at the cerebral peduncle (ROI-1) and a target ROI at the
      lower pons (ROI-2). ROI-1 was subsequently restricted to voxels that contained
      streamlines in the tract reconstruction, thus creating a sub-ROI. RESULTS: Mean
      fractional anisotropy (FA) and mean diffusivity values were highly reproducible
      by tract specific analysis, whereas simple ROI analysis yielded larger
      variabilities between operators. FA values were significantly lower in ALS
      patients than in normal controls in the tractography-derived sub-ROI (P= .01),
      but not in the seed or target ROIs. CONCLUSIONS: These results suggest, compared
      with simple ROI analysis, that tract-specific analysis using DTI fiber-tracking
      is more reliable and sensitive for detecting upper motor neuron pathology in ALS.

PMID- 18808654
TI  - Magnetic resonance imaging traits in siblings discordant for Alzheimer disease.
AB  - BACKGROUND: Magnetic resonance imaging (MRI) can aid clinical assessment of brain
      changes potentially correlated with Alzheimer disease (AD). MRI traits may
      improve our ability to identify genes associated with AD-outcomes. We evaluated
      semi-quantitative MRI measures as endophenotypes for genetic studies by assessing
      their association with AD in families from the Multi-Institutional Research in
      Alzheimer Genetic Epidemiology (MIRAGE) Study. METHODS: Discordant siblings from
      multiple ethnicities were ascertained through a single affected proband. Semi
      quantitative MRI measures were obtained for each individual. The association
      between continuous/ordinal MRI traits and AD were analyzed using generalized
      estimating equations. Medical history and Apolipoprotein E (APOE)epsilon4 status
      were evaluated as potential confounders. RESULTS: Comparisons of 214 affected and
      234 unaffected subjects from 229 sibships revealed that general cerebral atrophy,
      white matter hyperintensities (WMH), and mediotemporal atrophy differed
      significantly between groups (each at P < .0001) and varied by ethnicity. Age at
      MRI and duration of AD confounded all associations between AD and MRI traits.
      Among unaffected sibs, the presence of at least one APOEepsilon4 allele and MRI
      infarction was associated with more WMH after adjusting for age at MRI.
      CONCLUSION: The strong association between MRI traits and AD suggests that MRI
      traits may be informative endophenotypes for basic and clinical studies of AD. In
      particular, WMH may be a marker of vascular disease that contributes to AD
      pathogenesis.

PMID- 18808656
TI  - Magnetic resonance spectroscopic imaging detects abnormalities in normal
      appearing frontal lobe of patients with Sturge-Weber syndrome.
AB  - BACKGROUND: In Sturge-Weber syndrome (SWS), structural MRI abnormalities are most
      common in the posterior brain regions. Frontal lobe involvement increases the
      risk of motor impairment. The goal of this study was to determine whether
      Magnetic Resonance Spectroscopic Imaging (MRSI) can improve detection of frontal
      lobe involvement in children with SWS. METHODS: Sixteen children (age: .9-10.4
      years) with unilateral SWS underwent MRI with MRSI prospectively. N-acetyl
      aspartate (NAA) and choline asymmetries in the posterior and frontal regions were
      measured. RESULTS: Eight children presented normal-appearing frontal lobes on
      conventional MRI, but 7 of them showed abnormal NAA and/or choline content in the
      frontal lobe of the affected hemisphere. Lower frontal lobe gray matter NAA was
      associated with earlier onset of seizures (r= .76; P= .04) and impaired motor
      function (r=-.89, P < .001). Frontal NAA asymmetry was an independent predictor
      of motor function in a regression analysis (P= .01) CONCLUSION: MRSI is more
      sensitive than conventional structural MRI for detection of frontal lobe
      involvement in SWS. Decreased frontal lobe NAA is an excellent predictor of motor
      functions. Thus, MRSI can provide complementary information for the assessment of
      normal-appearing brain regions, and may assist prognosis evaluation in children
      with SWS.

PMID- 18808657
TI  - Subacute combined degeneration due to copper deficiency.

PMID- 18808659
TI  - Differential regulation of wild-type and mutant alpha-synuclein binding to
      synaptic membranes by cytosolic factors.
AB  - BACKGROUND: Alpha-Synuclein (alpha-syn), a 140 amino acid protein associated with
      presynaptic membranes in brain, is a major constituent of Lewy bodies in
      Parkinson's disease (PD). Three missense mutations (A30P, A53T and E46K) in the
      alpha-syn gene are associated with rare autosomal dominant forms of familial PD.
      However, the regulation of alpha-syn's cellular localization in neurons and the
      effects of the PD-linked mutations are poorly understood. RESULTS: In the present
      study, we analysed the ability of cytosolic factors to regulate alpha-syn binding
      to synaptic membranes. We show that co-incubation with brain cytosol
      significantly increases the membrane binding of normal and PD-linked mutant alpha
      syn. To characterize cytosolic factor(s) that modulate alpha-syn binding
      properties, we investigated the ability of proteins, lipids, ATP and calcium to
      modulate alpha-syn membrane interactions. We report that lipids and ATP are two
      of the principal cytosolic components that modulate Wt and A53T alpha-syn binding
      to the synaptic membrane. We further show that 1-O-hexadecyl-2-acetyl-sn-glycero
      3-phosphocholine (C16:0 PAF) is one of the principal lipids found in complex with
      cytosolic proteins and is required to enhance alpha-syn interaction with synaptic
      membrane. In addition, the impaired membrane binding observed for A30P alpha-syn
      was significantly mitigated by the presence of protease-sensitive factors in
      brain cytosol. CONCLUSION: These findings suggest that endogenous brain cytosolic
      factors regulate Wt and mutant alpha-syn membrane binding, and could represent
      potential targets to influence alpha-syn solubility in brain.

PMID- 18808660
TI  - Social differences in smoking and snuff use among Norwegian adolescents: a
      population based survey.
AB  - BACKGROUND: A change in pattern of tobacco use has been observed in the last
      decade in Norway. Snuff use and occasional smoking have to some degree replaced
      daily smoking among adolescents and young adults. Daily smoking is known to be
      negatively associated with social background factors, but little is known about
      these associations for other types of tobacco use. Our aim was to study different
      types of tobacco use among adolescents according to gender, educational
      ambitions, family background factors, and urbanization. METHODS: Cross-sectional,
      school-based study with 15 931 participants and response-rate 87%, conducted
      among 15 and 16 year olds during 2000-2004. RESULTS: More girls (33.8%) than boys
      (26.4%) were daily or occasional smokers, while more boys (21.4%) than girls
      (3.5%) were daily or occasional snuff users. Daily smoking was more common among
      adolescents planning vocational education, with single parents or poor family
      economy. Occasional smoking and snuff use (daily or occasionally) showed a
      similar, but less pronounced pattern regarding education and single parent
      families. Adolescents with parents from foreign countries were less likely to use
      tobacco. One exception was boys with parents from Muslim majority countries who
      had an increased risk of daily smoking. A typical combination user of both
      tobacco types was a Norwegian boy with divorced parents and ambitions to complete
      vocational studies or only one year of upper secondary school. CONCLUSION:
      Tobacco use in adolescents is mainly associated with low educational ambitions
      and less affluent self-reported family economy. Adolescents with divorced parents
      use more tobacco than those living with both parents. Public health initiatives
      to avoid or reduce tobacco use should mainly target adolescents in vocational
      studies and those leaving school early.

PMID- 18808661
TI  - Use of and attitudes towards the prescribing guidelines booklet in primary health
      care doctors.
AB  - BACKGROUND: In the region of Vastra Gotaland in Sweden, prescribing guidelines,
      drawn up by 24 expert groups and determined by the regional board for drugs, are
      since 2006 available in the form of an annually published booklet. This study
      investigates, for the first time, the use of and attitudes towards this
      publication. METHODS: A questionnaire was administered to doctors working in
      primary health care in the region of Vastra Gotaland in Sweden. Questions
      included characteristics of the responding doctor and use of the prescribing
      guidelines booklet, as well as attitude questions constructed as statements to
      which the responder should grade his level of agreement from 1 (total
      disagreement) to 6 (total agreement). RESULTS: Totally 603 filled-in
      questionnaires were returned (estimated response rate 60%). The majority of the
      doctors (n = 571, 97%) responded that they use the prescribing guidelines
      booklet, and when prescribing a drug for a new diagnosis, a drug from the booklet
      is chosen in most cases [median (25th - 75th percentile) 80 (75-90)]. However, at
      renewal of a drug prescription, active change to a drug from the prescribing
      guidelines booklet occurs less often [median (25th - 75th percentile) 50 (20
      70)]. The booklet also includes short therapy advice sections, which 231 doctors
      (42%) use every day and 191 (34%) use every week. The attitudes towards the
      prescribing guidelines booklet were generally positive. Doctors in privately run
      primary health care units and doctors running their own business were generally
      more negative and judged themselves to be less adherent to the prescribing
      guidelines booklet compared with doctors in publicly run primary health care
      units. CONCLUSION: The prescribing guidelines booklet is frequently used and is
      generally appreciated, though differences exist between subgroups of users.

PMID- 18808662
TI  - Initial impact and cost of a nationwide population screening campaign for
      diabetes in Brazil: a follow up study.
AB  - BACKGROUND: In 2001 Brazilian citizens aged 40 or older were invited to
      participate in a nationwide population screening program for diabetes. Capillary
      glucose screening tests and procedures for diagnostic confirmation were offered
      through the national healthcare system, diagnostic priority being given according
      to the severity of screening results. The objective of this study is to evaluate
      the initial impact of the program. METHODS: Positive testing was defined by a
      fasting capillary glucose >or= 100 mg/dL or casual glucose >or= 140 mg/dL. All
      test results were tabulated locally and aggregate data by gender and clinical
      categories were sent to the Ministry of Health. To analyze individual
      characteristics of screening tests performed, a stratified random sample of
      90,106 tests was drawn. To describe the actions taken for positive screenees, a
      random sub-sample of 4,906 positive screenees was actively followed up through
      home interviews. Main outcome measures considered were the number of diabetes
      cases diagnosed and cost per case detected and incorporated into healthcare.
      RESULTS: Of 22,069,905 screening tests performed, we estimate that 3,417,106 (95%
      CI 3.1 - 3.7 million) were positive and that 346,168 (290,454 - 401,852) new
      cases were diagnosed (10.1% of positives), 319,157 (92.2%) of these being
      incorporated into healthcare. The number of screening tests needed to detect one
      case of diabetes was 64. As many cases of untreated but previously known diabetes
      were also linked to healthcare providers during the Campaign, the estimated
      number needed screen to incorporate one case into the healthcare system was 58.
      Total screening and diagnostic costs were US$ 26.19 million, the cost per
      diabetes case diagnosed being US$ 76. Results were especially sensitive to
      proportion of individuals returning for diagnostic confirmation. CONCLUSION: This
      nationwide population-based screening program, conducted through primary
      healthcare services, demonstrates the feasibility, within the context of an
      organized national healthcare system, of screening campaigns for chronic
      diseases. Although overall costs were significant, cost per new case diagnosed
      was lower than previously reported. However, cost-effectiveness analysis based on
      more clinically significant outcomes needs to be conducted before this screening
      approach can be recommended in other settings.

PMID- 18808663
TI  - Diagnosing a popliteal venous aneurysm in a primary care setting: a case report.
AB  - INTRODUCTION: Popliteal venous aneurysms are uncommon but potentially fatal
      vascular disorders. They can be symptomatic or asymptomatic, mimicking different
      conditions. Popliteal venous aneurysms are possible sources of embolism. CASE
      PRESENTATION: A 68-year-old woman presented at a rural primary health care unit
      in Crete, Greece, reporting local symptoms of discomfort in the right popliteal
      fossa with pain during palpation. Colour Doppler ultrasonography revealed local
      widening and saccular dilatation in the right distal popliteal vein. The
      diagnosis of a popliteal venous aneurysm was formulated. CONCLUSION: Popliteal
      venous aneurysms are rare conditions, but are potentially more common than
      usually thought in daily practice. Physician awareness and access to ultrasound
      examination may allow for early diagnosis, before the occurrence of any
      thromboembolic or other major complication.

PMID- 18808664
TI  - A new tool for mini-open carpal tunnel release - the PSU retractor.
AB  - BACKGROUND: Mini-open carpal tunnel release has become increasingly popular for
      the treatment of carpal tunnel surgery. The main advantages are shortening
      recovery time and return-to-work time. However, the risk of neurovascular injury
      still remains worrisome. METHODS: In this study, we developed a new retractor
      (herein called the PSU retractor) modified from the widely used Senn retractor,
      with the aim of decreasing the risk of neurovascular problems from normal
      procedure. 3-Dimensional computer design software (SolidWorks Office Premium 2007
      SP3.1) was used to construct a 3-D PSU retractor prototype. An amputated arm from
      a 30-year-old woman diagnosed as synovial sarcoma at the shoulder was used to
      test the maximal visual length. A mini-surgical incision was performed at 3 cm
      distal to the transverse wrist crease and a tiny flexible ruler was inserted
      through the tunnel beneath the skin to measure the maximal visual length.
      RESULTS: Our new retractor showed significantly better maximal visual length
      compared to the Senn retractor (47.7(8.1) mm vs. 39.2(6.5) mm). In addition, most
      assessors expressed a higher satisfaction rate with the PSU retractor than with
      the Senn retractor (7.3 (1.9) vs. 6.3 (1.1)). CONCLUSION: In conclusion, we have
      developed a promising new retractor using a computer design program, which
      appears to be an improvement on the currently available equipment used for mini
      open carpal tunnel surgery. However, further clinical studies are needed to
      confirm our initial findings.

PMID- 18808665
TI  - Giardia assemblage A: human genotype in muskoxen in the Canadian Arctic.
AB  - As part of an ongoing program assessing the biodiversity and impacts of
      parasites in Arctic ungulates we examined 72 fecal samples from muskoxen on Banks
      Island, Northwest Territories, Canada for Giardia and Cryptosporidium.
      Cryptosporidium spp. were not detected, but 21% of the samples were positive for
      Giardia. Sequencing of four isolates of Giardia demonstrated G. duodenalis,
      Assemblage A, a zoonotic genotype.

PMID- 18808666
TI  - Correlation between Progetto Cuore risk score and early cardiovascular damage in
      never treated subjects.
AB  - BACKGROUND: Global cardiovascular risk is a new approach which allows the
      physicians to quantitate the prognosis of the patients. It is therefore possible
      that a score, based on the major cardiovascular risk factors, is correlated with
      some degree of cardiovascular anatomic damage. Since this hypothesis has been
      demonstrated with the Framingham risk score, we decided to verify it using
      another score (Progetto Cuore risk score), which is probably more precise in a
      european low-risk population, such as the italian one. METHODS: We studied 84
      italian caucasian subjects (50 males and 34 females) with elevated blood pressure
      and/or dyslipidemia plus other possible cardiovascular risk factors.The subjects
      have never been treated for these reasons. The following evaluations were
      performed: history, clinical and laboratory determinations, echocardiogram,
      carotid echodoppler. RESULTS: The recruited people were on the whole
      characterized by a low cardiovascular risk, as confirmed by the low scores of the
      Progetto Cuore. Simple linear regression analysis showed significant associations
      between some parameters of early cardiovascular damage (left ventricular mass,
      intima-media thickness, and an integrated measure of both the carotid wall
      thickness and the presence of a plaque, called Carotid score) and some
      predictors. The highest significance was found between the cardiovascular
      structural results and the Progetto Cuore score. In a multivariate regression
      analysis our model, which included factors potentially linked to the
      cardiovascular anatomic changes, demonstrated that the Carotid score was
      significantly associated with age, sex and pulse pressure; intima-media thickness
      with the same factors and, in addition, with the body mass index; left
      ventricular mass with sex, pulse pressure and body mass index. CONCLUSION: Our
      paper confirms previous studies about the association between a comprehensive
      risk score and signs of early cardiovascular damage. A temporally limited
      exposure to cardiovascular risk factors, in particular to blood pressure, is
      already able to induce significant changes in both the heart structure and the
      vascular wall. Also in a european low-risk population the use of a cardiovascular
      risk score program, such as the Progetto Cuore in Italy, allows a quite precise
      estimation of the possible cardiovascular damage.

PMID- 18808667
TI  - Localisation of laminin within Plasmodium berghei oocysts and the midgut
      epithelial cells of Anopheles stephensi.
AB  - BACKGROUND: Oocysts of the malaria parasite form and develop in close proximity
      to the mosquito midgut basal lamina and it has been proposed that components of
      this structure play a crucial role in the development and maturation of oocysts
      that produce infective sporozoites. It is further suggested that oocysts
      incorporate basal lamina proteins into their capsule and that this provides them
      with a means to evade recognition by the mosquito's immune system. The site of
      production of basal lamina proteins in insects is controversial and it is still
      unclear whether haemocytes or midgut epithelial cells are the main source of
      components of the mosquito midgut basal lamina. Of the multiple molecules that
      compose the basal lamina, laminin is known to interact with a number of
      Plasmodium proteins. In this study, the localisation of mosquito laminin within
      the capsule and cytoplasm of Plasmodium berghei oocysts and in the midgut
      epithelial cells of Anopheles stephensi was investigated. RESULTS: An
      ultrastructural examination of midgut sections from infected and uninfected An.
      stephensi was performed. Post-embedded immunogold labelling demonstrated the
      presence of laminin within the mosquito basal lamina. Laminin was also detected
      on the outer surface of the oocyst capsule, incorporated within the capsule and
      associated with sporozoites forming within the oocysts. Laminin was also found
      within cells of the midgut epithelium, providing support for the hypothesis that
      these cells contribute towards the formation of the midgut basal lamina.
      CONCLUSION: We suggest that ookinetes may become coated in laminin as they pass
      through the midgut epithelium. Thereafter, laminin secreted by midgut epithelial
      cells and/or haemocytes, binds to the outer surface of the oocyst capsule and
      that some passes through and is incorporated into the developing oocysts. The
      localisation of laminin on sporozoites was unexpected and the importance of this
      observation is less clear.

PMID- 18808668
TI  - Employing conservation of co-expression to improve functional inference.
AB  - BACKGROUND: Observing co-expression between genes suggests that they are
      functionally coupled. Co-expression of orthologous gene pairs across species may
      improve function prediction beyond the level achieved in a single species.
      RESULTS: We used orthology between genes of the three different species S.
      cerevisiae, D. melanogaster, and C. elegans to combine co-expression across two
      species at a time. This led to increased function prediction accuracy when we
      incorporated expression data from either of the other two species and even
      further increased when conservation across both of the two other species was
      considered at the same time. Employing the conservation across species to
      incorporate abundant model organism data for the prediction of protein
      interactions in poorly characterized species constitutes a very powerful
      annotation method. CONCLUSION: To be able to employ the most suitable co
      expression distance measure for our analysis, we evaluated the ability of four
      popular gene co-expression distance measures to detect biologically relevant
      interactions between pairs of genes. For the expression datasets employed in our
      co-expression conservation analysis above, we used the GO and the KEGG PATHWAY
      databases as gold standards. While the differences between distance measures were
      small, Spearman correlation showed to give most robust results.

PMID- 18808669
TI  - Tv-RIO1 - an atypical protein kinase from the parasitic nematode Trichostrongylus
      vitrinus.
AB  - BACKGROUND: Protein kinases are key enzymes that regulate a wide range of
      cellular processes, including cell-cycle progression, transcription, DNA
      replication and metabolic functions. These enzymes catalyse the transfer of
      phosphates to serine, threonine and tyrosine residues, thus playing functional
      roles in reversible protein phosphorylation. There are two main groups, namely
      eukaryotic protein kinases (ePKs) and atypical protein kinases (aPKs); RIO
      kinases belong to the latter group. While there is some information about RIO
      kinases and their roles in animals, nothing is known about them in parasites.
      This is the first study to characterise a RIO1 kinase from any parasite. RESULTS:
      A full-length cDNA (Tv-rio-1) encoding a RIO1 protein kinase (Tv-RIO1) was
      isolated from the economically important parasitic nematode Trichostrongylus
      vitrinus (Order Strongylida). The uninterrupted open reading frame (ORF) of 1476
      nucleotides encoded a protein of 491 amino acids, containing the characteristic
      RIO1 motif LVHADLSEYNTL. Tv-rio-1 was transcribed at the highest level in the
      third-stage larva (L3), and a higher level in adult females than in males.
      Comparison with homologues from other organisms showed that protein Tv-RIO1 had
      significant homology to related proteins from a range of metazoans and plants.
      Amino acid sequence identity was most pronounced in the ATP-binding motif, active
      site and metal binding loop. Phylogenetic analyses of selected amino acid
      sequence data revealed Tv-RIO1 to be most closely related to the proteins in the
      species of Caenorhabditis. A structural model of Tv-RIO1 was constructed and
      compared with the published crystal structure of RIO1 of Archaeoglobus fulgidus
      (Af-Rio1). CONCLUSION: This study provides the first insights into the RIO1
      protein kinases of nematodes, and a foundation for further investigations into
      the biochemical and functional roles of this molecule in biological processes in
      parasitic nematodes.

PMID- 18808670
TI  - Generation of diverse neuronal subtypes in cloned populations of stem-like cells.
AB  - BACKGROUND: The central nervous tissue contains diverse subtypes of neurons with
      characteristic morphological and physiological features and different
      neurotransmitter phenotypes. The generation of neurons with defined
      neurotransmitter phenotypes seems to be governed by factors differently expressed
      along the anterior-posterior and dorsal-ventral body axes. The mechanisms of the
      cell-type determination, however, are poorly understood. Selected neuronal
      phenotypes had been generated from embryonic stem (ES) cells, but similar results
      were not obtained on more restricted neural stem cells, presumably due to the
      lack of homogeneous neural stem cell populations as a starting material. RESULTS:
      In the presented work, the establishment of different neurotransmitter phenotypes
      was investigated in the course of in vitro induced neural differentiation of a
      one-cell derived neuroectodermal cell line, in conjunction with the activation of
      various region-specific genes. For comparison, similar studies were carried out
      on the R1 embryonic stem (ES) and P19 multipotent embryonic carcinoma (EC) cells.
      In response to a short treatment with all-trans retinoic acid, all cell lines
      gave rise to neurons and astrocytes. Non-induced neural stem cells and self
      renewing cells persisting in differentiated cultures, expressed "stemness genes"
      along with early embryonic anterior-dorsal positional genes, but did not express
      the investigated CNS region-specific genes. In differentiating stem-like cell
      populations, on the other hand, different region-specific genes, those expressed
      in non-overlapping regions along the body axes were activated. The potential for
      diverse regional specifications was induced in parallel with the initiation of
      neural tissue-type differentiation. In accordance with the wide regional
      specification potential, neurons with different neurotransmitter phenotypes
      developed. Mechanisms inherent to one-cell derived neural stem cell populations
      were sufficient to establish glutamatergic and GABAergic neuronal phenotypes but
      failed to manifest cathecolaminergic neurons. CONCLUSION: The data indicate that
      genes involved in positional determination are activated along with pro-neuronal
      genes in conditions excluding any outside influences. Interactions among
      progenies of one cell derived neural stem cells are sufficient for the activation
      of diverse region specific genes and initiate different routes of neuronal
      specification.

PMID- 18808671
TI  - pi-Turns: types, systematics and the context of their occurrence in protein
      structures.
AB  - BACKGROUND: For a proper understanding of protein structure and folding it is
      important to know if a polypeptide segment adopts a conformation inherent in the
      sequence or it depends on the context of its flanking secondary structures. Turns
      of various lengths have been studied and characterized starting from three
      residue gamma-turn to six-residue pi-turn. The Schellman motif occurring at the C
      terminal end of alpha-helices is a classical example of hydrogen bonded pi-turn
      involving residues at (i) and (i+5) positions. Hydrogen bonded and non-hydrogen
      bonded beta- and alpha-turns have been identified previously; likewise, a
      systematic characterization of pi-turns would provide valuable insight into turn
      structures. RESULTS: An analysis of protein structures indicates that at least
      20% of pi-turns occur independent of the Schellman motif. The two categories of
      pi-turns, designated as pi-HB and SCH, have been further classified on the basis
      of backbone conformation and both have AAAa as the major class. They differ in
      the residue usage at position (i+1), the former having a large preference for Pro
      that is absent in the latter. As in the case of shorter length beta- and alpha
      turns, pi-turns have also been identified not only on the basis of the existence
      of hydrogen bond, but also using the distance between terminal C alpha-atoms, and
      this resulted in a comparable number of non-hydrogen-bonded pi-turns (pi-NHB).
      The presence of shorter beta- and alpha-turns within all categories of pi-turns,
      the subtle variations in backbone torsion angles along the turn residues, the
      location of the turns in the context of tertiary structures have been studied.
      CONCLUSION: pi-turns have been characterized, first using hydrogen bond and the
      distance between C alpha atoms of the terminal residues, and then using backbone
      torsion angles. While the Schellman motif has a structural role in helix
      termination, many of the pi-HB turns, being located on surface cavities, have
      functional role and there is also sequence conservation.

PMID- 18808672
TI  - Non-homogeneous models of sequence evolution in the Bio++ suite of libraries and
      programs.
AB  - BACKGROUND: Accurately modeling the sequence substitution process is required for
      the correct estimation of evolutionary parameters, be they phylogenetic
      relationships, substitution rates or ancestral states; it is also crucial to
      simulate realistic data sets. Such simulation procedures are needed to estimate
      the null-distribution of complex statistics, an approach referred to as
      parametric bootstrapping, and are also used to test the quality of phylogenetic
      reconstruction programs. It has often been observed that homologous sequences can
      vary widely in their nucleotide or amino-acid compositions, revealing that
      sequence evolution has changed importantly among lineages, and may therefore be
      most appropriately approached through non-homogeneous models. Several programs
      implementing such models have been developed, but they are limited in their
      possibilities: only a few particular models are available for likelihood
      optimization, and data sets cannot be easily generated using the resulting
      estimated parameters. RESULTS: We hereby present a general implementation of non
      homogeneous models of substitutions. It is available as dedicated classes in the
      Bio++ libraries and can hence be used in any C++ program. Two programs that use
      these classes are also presented. The first one, Bio++ Maximum Likelihood
      (BppML), estimates parameters of any non-homogeneous model and the second one,
      Bio++ Sequence Generator (BppSeqGen), simulates the evolution of sequences from
      these models. These programs allow the user to describe non-homogeneous models
      through a property file with a simple yet powerful syntax, without any
      programming required. CONCLUSION: We show that the general implementation
      introduced here can accommodate virtually any type of non-homogeneous models of
      sequence evolution, including heterotachous ones, while being computer efficient.
      We furthermore illustrate the use of such general models for parametric
      bootstrapping, using tests of non-homogeneity applied to an already published
      ribosomal RNA data set.

PMID- 18808673
TI  - beta-Estradiol attenuates the anti-HIV-1 efficacy of Stavudine (D4T) in primary
      PBL.
AB  - BACKGROUND: Female hormones are known to play an important role in predisposition
      for many infectious diseases. Recent work suggests there are gender effects in
      HIV/AIDS progression. Here we ask whether the sex steroid hormone beta-estradiol
      affects the replication of HIV-1 or the efficacy of a common anti-retroviral
      drug, Stavudine (D4T). RESULTS: Human PBL were infected with HIV-1 in the
      presence or absence of combinations of sex steroid hormones and the anti
      retroviral drug, D4T. After seven days in culture, viral supernatants were
      assayed for HIV-1 p24 protein. beta-estradiol resulted in a modest inhibition of
      HIV-1 replication of approximately 26%. However, 2 nM beta-estradiol increased
      the amount of HIV-1 replication in the presence of 50 nM D4T from a baseline of
      33% (+/- SE = 5.4) to 74% (+/- SE = 5.4) of control virus levels in the absence
      of drug. Both results were statistically highly significant (p < 0.001). beta
      estradiol did not increase the replication of a D4T-resistant strain of HIV in
      the presence of D4T. The effects were unlikely to be due to general cell
      inhibition or toxicity because these concentrations of drug and hormone cause no
      cytotoxicity in PBL as measured by trypan blue exclusion. CONCLUSION: beta
      estradiol inhibited both HIV-1 replication in primary human PBL and the
      antiretroviral efficacy of D4T in PBL cultures. To optimize antiretroviral drug
      therapy, it may be necessary to monitor patient hormonal status.

PMID- 18808674
TI  - Homonuclear 1H NMR and circular dichroism study of the HIV-1 Tat Eli variant.
AB  - BACKGROUND: The HIV-1 Tat protein is a promising target to develop AIDS
      therapies, particularly vaccines, due to its extracellular role that protects HIV
      1-infected cells from the immune system. Tat exists in two different lengths, 86
      or 87 residues and 99 or 101 residues, with the long form being predominant in
      clinical isolates. We report here a structural study of the 99 residue Tat Eli
      variant using 2D liquid-state NMR, molecular modeling and circular dichroism.
      RESULTS: Tat Eli was obtained from solid-phase peptide synthesis and the purified
      protein was proven biologically active in a trans-activation assay. Circular
      dichroism spectra at different temperatures up to 70 degrees C showed that Tat
      Eli is not a random coil at 20 degrees C. Homonuclear 1H NMR spectra allowed us
      to identify 1639 NMR distance constraints out of which 264 were interresidual.
      Molecular modeling satisfying at least 1474 NMR constraints revealed the same
      folding for different model structures. The Tat Eli model has a core region
      composed of a part of the N-terminus including the highly conserved Trp 11. The
      extra residues in the Tat Eli C-terminus protrude from a groove between the basic
      region and the cysteine-rich region and are well exposed to the solvent.
      CONCLUSION: We show that active Tat variants share a similar folding pattern
      whatever their size, but mutations induce local structural changes.

PMID- 18808675
TI  - Determinants of health-related quality of life in elderly in Tehran, Iran.
AB  - BACKGROUND: As Iran started to experience population ageing, it is important to
      consider and address the elderly people's needs and concerns, which might have
      direct impacts on their well-being and quality of life. There have been only a
      few researches into different aspects of life of the elderly population in Iran
      including their health-related quality of life. The purpose of this study was to
      measure health-related quality of life (HRQoL) of elderly Iranians and to
      identify its some determinant factors. METHODS: This was a cross-sectional survey
      of a random sample of community residents of Tehran aged 65 years old and over.
      HRQoL was measured using the Short From Health Survey (SF-36). The study
      participants were interviewed at their homes. Uni-variate analysis was performed
      for group comparison and logistic regression analysis conducted to predict
      quality of life determinants. RESULTS: In all, 400 elderly Iranian were
      interviewed. The majority of the participants were men (56.5%) and almost half of
      the participants were illiterate (n = 199, 49.8%). Eighty-five percent of the
      elderly were living with their family or relatives and about 70% were married.
      Only 12% of participants evaluated their economic status as being good and most
      of people had moderate or poor economic status. The mean scores for the SF-36
      subscales ranged from 70.0 (SD = 25.9) for physical functioning to 53.5 (SD =
      29.1) for bodily pain and in general, the respondents significantly showed better
      condition on mental component of the SF-36 than its physical component (mean
      scores 63.8 versus 55.0). Performing uni-variate analysis we found that women
      reported significantly poorer HRQoL. Multiple logistic regression analysis showed
      that for the physical component summary score of the SF-36, age, gender,
      education and economic status were significant determinants of poorer physical
      health-related quality of life; while for the mental component summary score only
      gender and economic status were significant determinants of poorer mental health
      related quality of life. The analysis suggested that the elderly people's
      economic status was the most significant predictor of their HRQoL. CONCLUSION:
      The study findings, although with a small number of participants, indicate that
      elderly people living in Tehran, Iran suffer from relatively poor HRQoL;
      particularly elderly women and those with lower education. Indeed to improve
      quality of life among elderly Iranians much more attention should be paid to all
      aspects of their life including their health, and economic status.

PMID- 18808676
TI  - Serum free light chain measurement aids the diagnosis of myeloma in patients with
      severe renal failure.
AB  - BACKGROUND: Monoclonal free light chains (FLCs) frequently cause rapidly
      progressive renal failure in patients with multiple myeloma. Immunoassays which
      provide quantitative measurement of FLCs in serum, have now been adopted into
      screening algorithms for multiple myeloma and other lymphoproliferative
      disorders. The assays indicate monoclonal FLC production by the presence of an
      abnormal kappa to lambda FLC ratio (reference range 0.26-1.65). Previous work,
      however, has demonstrated that in patients with renal failure the FLC ratio can
      be increased above normal with no other evidence of monoclonal proteins
      suggesting that in this population the range should be extended (reference range
      0.37-3.1). This study evaluated the diagnostic sensitivity and specificity of the
      immunoassays in patients with severe renal failure. METHODS: Sera from 142
      patients with new dialysis-dependent renal failure were assessed by serum protein
      electrophoresis (SPE), FLC immunoassays and immunofixation electrophoresis. The
      sensitivity and specificity of the FLC ratio's published reference range was
      compared with the modified renal reference range for identifying patients with
      multiple myeloma; by receiver operating characteristic curve analysis. RESULTS:
      Forty one patients had a clinical diagnosis of multiple myeloma; all of these
      patients had abnormal serum FLC ratios. The modified FLC ratio range increased
      the specificity of the assays (from 93% to 99%), with no loss of sensitivity.
      Monoclonal FLCs were identified in the urine from 23 of 24 patients assessed.
      CONCLUSION: Measurement of serum FLC concentrations and calculation of the serum
      kappa/lambda ratio is a convenient, sensitive and specific method for identifying
      monoclonal FLC production in patients with multiple myeloma and acute renal
      failure. Rapid diagnosis in these patients will allow early initiation of disease
      specific treatment, such as chemotherapy plus or minus therapies for direct
      removal of FLCs.

PMID- 18808678
TI  - Criteria-based audit to improve a district referral system in Malawi: a pilot
      study.
AB  - BACKGROUND: To study the feasibility of using criteria-based audit to improve a
      district referral system. METHODS: A criteria-based audit was used to assess the
      Salima District referral system in Malawi. A retrospective review of 60 obstetric
      emergencies referred from 12 health centres was conducted and compared with prior
      established standards for optimal referral of emergencies. Recommendations were
      made and implemented. Three months later, a re-audit was conducted (62 cases).
      RESULTS: There were significant improvements in 4 out of 7 standards: adequate
      resuscitation before referral (33.3% vs 88.7%; p = 0.001); delay of less than 2
      hours from the time the ambulance is called to when the ambulance brought the
      patient to the hospital (42.8% vs 88.3%; p = 0.014); clinician attends to patient
      within 30 minutes of arrival to hospital (30.8% vs 92.6%; p = 0.001) and feedback
      given to the referring health centres (1.7% vs 91.9%; p <0.001). The rest of the
      three standards showed a high level of attainment (>95%) in both the initial
      audit and the re-audit: referred patients accompanied by a referral form;
      ambulances are available at all times and the district hospital is informed
      through short-wave radio by the health centre when a patient is referred.
      CONCLUSION: Criteria-based audit can improve the ability of a district referral
      system to handle obstetric emergencies in countries with limited resources.

PMID- 18808679
TI  - Ischemic volvulus of the transverse colon: A case report and review of
      literature.
AB  - A 75-year old male presented to the emergency room with worsening abdominal pain
      and distension. Plain radiographs were suggestive of a large bowel obstruction
      due to volvulus. An attempt to detorse the volvulus and decompress the colon
      endoscopically failed, after which the patient was taken for an exploratory
      laparotomy. A transverse colon volvulus was found, and an extended right
      hemicolectomy and ileostomy was performed. We discuss the diagnosis and
      management of transverse colon volvulus and review the pertinent literature.

PMID- 18808677
TI  - HIV-1 Nef: at the crossroads.
AB  - The development of anti-virals has blunted the AIDS epidemic in the Western world
      but globally the epidemic has not been curtailed. Standard vaccines have not
      worked, and attenuated vaccines are not being developed because of safety
      concerns. Interest in attenuated vaccines has centered on isolated cases of
      patients infected with HIV-1 containing a deleted nef gene. Nef is a
      multifunctional accessory protein that is necessary for full HIV-1 virulence.
      Unfortunately, some patients infected with the nef-deleted virus eventually lose
      their CD4+ T cells to levels indicating progression to AIDS. This renders the
      possibility of an attenuated HIV-1 based solely on a deleted nef remote. In this
      review we discuss the knowledge gained both from the study of these patients and
      from in vitro investigations of Nef function to assess the possibility of
      developing new anti-HIV-1 drugs based on Nef. Specifically, we consider CD4
      downregulation, major histocompatibility complex I downregulation, Pak2
      activation, and enhancement of virion infectivity. We also consider the recent
      proposal that simian immunodeficiency viruses are non-pathogenic in their hosts
      because they have Nefs that downregulate CD3, but HIV-1 is pathogenic because its
      Nef fails to downregulate CD3. The possibility of incorporating the CD3
      downregulation function into HIV-1 Nef as a therapeutic option is also
      considered. Finally, we conclude that inhibiting the CD4 downregulation function
      is the most promising Nef-targeted approach for developing a new anti-viral as a
      contribution to combating AIDS.

PMID- 18808680
TI  - How to engage Cofilin.
AB  - In HIV-infected people, resting CD4+ T cells are the main reservoir of latent
      virus and the reason for the failure of drug therapy to cure HIV infection.
      Still, we do not have a complete understanding of the factors regulating HIV
      replication in these cells. A recent paper in Cell describes a new trick that the
      virus uses to infect resting T cells. Interaction between the viral gp120 and
      cellular HIV co-receptor, CXCR4, during viral entry initiates signaling that
      activates cofilin, the main regulator of actin polymerization. As a result of
      this activation, actin is depolymerized, thus destroying the natural barrier to
      HIV replication. I discuss implications of this study for our understanding of
      HIV biology and development of novel anti-HIV therapeutic approaches.

PMID- 18808681
TI  - Human T-cell leukemia virus type I infects human lung epithelial cells and
      induces gene expression of cytokines, chemokines and cell adhesion molecules.
AB  - BACKGROUND: Human T-cell leukemia virus type I (HTLV-I) is associated with
      pulmonary diseases, characterized by bronchoalveolar lymphocytosis, which
      correlates with HTLV-I proviral DNA in carriers. HTLV-I Tax seems to be involved
      in the development of such pulmonary diseases through the local production of
      inflammatory cytokines and chemokines in T cells. However, little is known about
      induction of these genes by HTLV-I infection in lung epithelial cells. RESULTS:
      We tested infection of lung epithelial cells by HTLV-I by coculture studies in
      which A549 alveolar and NCI-H292 tracheal epithelial cell lines were cocultured
      with MT-2, an HTLV-I-infected T-cell line. Changes in the expression of several
      cellular genes were assessed by reverse transcription-polymerase chain reaction,
      enzyme-linked immunosorbent assay and flow cytometry. Coculture with MT-2 cells
      resulted in infection of lung epithelial cells as confirmed by detection of
      proviral DNA, HTLV-I Tax expression and HTLV-I p19 in the latter cells. Infection
      was associated with induction of mRNA expression of various cytokines, chemokines
      and cell adhesion molecule. NF-kappaB and AP-1 were also activated in HTLV-I
      infected lung epithelial cells. In vivo studies showed Tax protein in lung
      epithelial cells of mice bearing Tax and patients with HTLV-I-related pulmonary
      diseases. CONCLUSION: Our results suggest that HTLV-I infects lung epithelial
      cells, with subsequent production of cytokines, chemokines and cell adhesion
      molecules through induction of NF-kappaB and AP-1. These changes can contribute
      to the clinical features of HTLV-I-related pulmonary diseases.

PMID- 18808682
TI  - Direct Vpr-Vpr interaction in cells monitored by two photon fluorescence
      correlation spectroscopy and fluorescence lifetime imaging.
AB  - BACKGROUND: The human immunodeficiency virus type 1 (HIV-1) encodes several
      regulatory proteins, notably Vpr which influences the survival of the infected
      cells by causing a G2/M arrest and apoptosis. Such an important role of Vpr in
      HIV-1 disease progression has fuelled a large number of studies, from its 3D
      structure to the characterization of specific cellular partners. However, no
      direct imaging and quantification of Vpr-Vpr interaction in living cells has yet
      been reported. To address this issue, eGFP- and mCherry proteins were tagged by
      Vpr, expressed in HeLa cells and their interaction was studied by two photon
      fluorescence lifetime imaging microscopy and fluorescence correlation
      spectroscopy. RESULTS: Results show that Vpr forms homo-oligomers at or close to
      the nuclear envelope. Moreover, Vpr dimers and trimers were found in the
      cytoplasm and in the nucleus. Point mutations in the three alpha helices of Vpr
      drastically impaired Vpr oligomerization and localization at the nuclear envelope
      while point mutations outside the helical regions had no effect. Theoretical
      structures of Vpr mutants reveal that mutations within the alpha-helices could
      perturb the leucine zipper like motifs. The DeltaQ44 mutation has the most
      drastic effect since it likely disrupts the second helix. Finally, all Vpr point
      mutants caused cell apoptosis suggesting that Vpr-mediated apoptosis functions
      independently from Vpr oligomerization. CONCLUSION: We report that Vpr
      oligomerization in HeLa cells relies on the hydrophobic core formed by the three
      alpha helices. This oligomerization is required for Vpr localization at the
      nuclear envelope but not for Vpr-mediated apoptosis.

PMID- 18808683
TI  - Heat stress-responsive transcriptome analysis in heat susceptible and tolerant
      wheat (Triticum aestivum L.) by using Wheat Genome Array.
AB  - BACKGROUND: Wheat is a major crop in the world, and the high temperature stress
      can reduce the yield of wheat by as much as 15%. The molecular changes in
      response to heat stress are poorly understood. Using GeneChip Wheat Genome Array,
      we analyzed genome-wide gene expression profiles in the leaves of two wheat
      genotypes, namely, heat susceptible 'Chinese Spring' (CS) and heat tolerant
      'TAM107' (TAM). RESULTS: A total of 6560 (approximately 10.7%) probe sets
      displayed 2-fold or more changes in expression in at least one heat treatment
      (false discovery rate, FDR, alpha = 0.001). Except for heat shock protein (HSP)
      and heat shock factor (HSF) genes, these putative heat responsive genes encode
      transcription factors and proteins involved in phytohormone
      biosynthesis/signaling, calcium and sugar signal pathways, RNA metabolism,
      ribosomal proteins, primary and secondary metabolisms, as well as proteins
      related to other stresses. A total of 313 probe sets were differentially
      expressed between the two genotypes, which could be responsible for the
      difference in heat tolerance of the two genotypes. Moreover, 1314 were
      differentially expressed between the heat treatments with and without pre
      acclimation, and 4533 were differentially expressed between short and prolonged
      heat treatments. CONCLUSION: The differences in heat tolerance in different wheat
      genotypes may be associated with multiple processes and mechanisms involving
      HSPs, transcription factors, and other stress related genes. Heat acclimation has
      little effects on gene expression under prolonged treatments but affects gene
      expression in wheat under short-term heat stress. The heat stress responsive
      genes identified in this study will facilitate our understanding of molecular
      basis for heat tolerance in different wheat genotypes and future improvement of
      heat tolerance in wheat and other cereals.

PMID- 18808684
TI  - Waist circumference and waist-to-height ratio of Hong Kong Chinese children.
AB  - BACKGROUND: Central body fat is a better predictor than overall body fat for
      cardiovascular (CV) risk factors in both adults and children. Waist circumference
      (WC) has been used as a proxy measure of central body fat. Children at high CV
      risk may be identified by WC measurements. Waist-to-height ratio (WHTR) has been
      proposed as an alternative, conveniently age-independent measure of CV risk
      although WHTR percentiles have not been reported. We aim to provide age- and sex
      specific reference values for WC and WHTR in Hong Kong Chinese children. METHODS:
      Cross sectional study in a large representative sample of 14,842 children aged 6
      to 18 years in 2005/6. Sex-specific descriptive statistics for whole-year age
      groups and smoothed percentile curves of WC and WHTR were derived and presented.
      RESULTS: WC increased with age, although less after age 14 years in girls. WHTR
      decreased with age (particularly up to age 14). WHTR correlated less closely than
      WC with BMI (r = 0.65, 0.59 cf. 0.93, 0.91, for boys and girls respectively).
      CONCLUSION: Reference values and percentile curves for WC and WHRT of Chinese
      children and adolescents are provided. Both WC and WHTR are age dependent. Since
      the use of WHRT does not obviate the need for age-related reference standards,
      simple WC measurement is a more convenient method for central fat estimation than
      WHRT.

PMID- 18808685
TI  - Transformation of the rodent malaria parasite Plasmodium chabaudi and generation
      of a stable fluorescent line PcGFPCON.
AB  - BACKGROUND: The rodent malaria parasite Plasmodium chabaudi has proven of great
      value in the analysis of fundamental aspects of host-parasite-vector interactions
      implicated in disease pathology and parasite evolutionary ecology. However, the
      lack of gene modification technologies for this model has precluded more direct
      functional studies. METHODS: The development of in vitro culture methods to yield
      P. chabaudi schizonts for transfection and conditions for genetic modification of
      this rodent malaria model are reported. RESULTS: Independent P. chabaudi gene
      integrant lines that constitutively express high levels of green fluorescent
      protein throughout their life cycle have been generated. CONCLUSION: Genetic
      modification of P. chabaudi is now possible. The production of genetically
      distinct reference lines offers substantial advances to our understanding of
      malaria parasite biology, especially interactions with the immune system during
      chronic infection.

PMID- 18808686
TI  - A phase I radiation dose-escalation study to determine the maximal dose of
      radiotherapy in combination with weekly gemcitabine in patients with locally
      advanced pancreatic adenocarcinoma.
AB  - BACKGROUND: The primary objective of this study was to determine the maximum
      tolerated dose (MTD) of escalating doses of radiotherapy (RT) concomitantly with
      a fixed dose of gemcitabine (300 mg/m2/week) within the same overall treatment
      time. METHODS: Thirteen patients were included. Gemcitabine 300 mg/m2/week was
      administered prior to RT. The initial dose of RT was 45 Gy in 1.8 Gy fractions,
      escalated by adding 5 fractions of 1.8 Gy (one/week) to a dose of 54 Gy with a
      total duration kept at 5 weeks. All patients received a dynamic MRI to assess the
      pancreatic respiratory related movements. Toxicity was scored using the RTOG
      EORTC toxicity criteria. RESULTS: Three of six patients experienced an acute dose
      limiting toxicity (DLT) at the 54 Gy dose level. For these patients a grade III
      gastro-intestinal toxicity (GI) was noted. Patients treated at the 45 Gy dose
      level tolerated therapy without DLT. The 54 Gy dose level was designated as the
      MTD and was deemed not suitable for further investigation. Between both dose
      levels, there was a significant difference in percentage weight loss (p = 0.006)
      and also in cumulative GI toxicity (p = 0.027). There was no grade 3 toxicity in
      the 45 Gy cohort versus 4 grade 3 toxicity events in the 54 Gy cohort. The mean
      dose to the duodenum was significantly higher in the 54 Gy cohort (38.45 Gy vs.
      51.82 Gy; p = 0.001). CONCLUSION: Accelerated dose escalation to a total dose of
      54 Gy with 300 mg/m2/week gemcitabine was not feasible. GI toxicity was the DLT.
      Retrospectively, the dose escalation of 9 Gy by accelerated radiotherapy might
      have been to large. A dose of 45 Gy is recommended. Considering the good patient
      outcomes, there might be a role for the investigation of a fixed dose of
      gemcitabine and concurrent RT with small fractions (1.8 Gy/day) in borderline
      resectable or unresectable non-metastatic locally advanced pancreatic cancer.

PMID- 18808687
TI  - Influence of Ketotifen, Cromolyn Sodium, and Compound 48/80 on the survival rates
      after intestinal ischemia reperfusion injury in rats.
AB  - BACKGROUND: Mast cells were associated with intestinal ischemia-reperfusion
      injury, the study was to observe the influence of Ketotifen, Cromolyn Sdium(CS),
      and Compound 48/80(CP) on the survival rates on the third day after intestinal
      ischemia-reperfusion injury in rats. METHODS: 120 healthy Sprague-Dawley rats
      were randomly divided into 5 groups, Sham-operated group (group S), model group
      (group M), group K, group C and group CP. Intestinal damage was triggered by
      clamping the superior mesenteric artery for 75 minutes, group K, C, and CP were
      treated with kotifen 1 mg.kg-1, CS 50 mg.kg-1, and CP 0.75 mg.kg-1 i.v. at 5 min
      before reperfusion and once daily for three days following reperfusion
      respectively. Survival rate in each group was recorded during the three days
      after reperfusion. All the surviving rats were killed for determining the
      concentration of serum glutamic-oxaloacetic transaminase(AST), glutamic pyruvic
      transaminase(ALT), the ratio of AST compare ALT(S/L), total protein(TP),
      albumin(ALB), globulin(GLB), the ratio of ALB compare GLB(A/G), phosphocreatine
      kinase(CK), lactate dehydrogenase(LDH), urea nitrogen(BUN) and creatinine(CRE) at
      the 3rd day after reperfusion. And ultrastructure of IMMC, Chiu's score, lung
      histology, IMMC counts, the levels of TNF-alpha, IL-1beta, IL-6 and IL-10 of the
      small intestine were detected at the same time. RESULTS: Intestinal ischemia
      reperfusion injury reduced the survival rate. The concentrations of TP, ALB and
      level of IL-10 in intestine in group M decreased significantly while the
      concentrations of S/L, LDH and the levels of IL-6 and TNF-alpha in intestine
      increased significantly compared with group S (P < 0.05). Treatment with
      Ketotifen and CS increased the survival rate compared with group M (P < 0.05),
      attenuated the down-regulation or up-regulation of the above index (P < 0.05).
      Treatment with CP decreased the survival rate on the 3rd day after reperfusion
      compared with group M(P < 0.05). Group K and C had better morphology in IMMC in
      the small intestine and in the lungs than in group M and CP, although the Chiu's
      score and IMMC counts remained the same in the five groups(P > 0.05). CONCLUSION:
      Mast cell inhibition after ischemia prior to reperfusion and following
      reperfusion may decrease the multi-organ injury induced by intestine ischemia
      reperfusion, and increase the survival rates.

PMID- 18808688
TI  - Prognostic impact of tumour-specific HMG-CoA reductase expression in primary
      breast cancer.
AB  - INTRODUCTION: We have previously reported that tumour-specific expression of the
      rate-limiting enzyme, 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMG
      CoAR), in the mevalonate pathway is associated with more favourable tumour
      parameters in breast cancer. In the present study, we examined the prognostic
      value of HMG-CoAR expression in a large cohort of primary breast cancer patients
      with long-term follow up. METHODS: The expression of HMG-CoAR was assessed by
      immunohistochemistry on tissue microarrays with tumour specimens from 498
      consecutive cases of breast cancer with a median follow-up of 128 months. Kaplan
      Meier analysis and Cox proportional hazards modelling were used to estimate the
      rate of recurrence-free survival (RFS) and breast cancer specific survival
      (BCSS). RESULTS: In line with our previous findings, tumour-specific HMG-CoAR
      expression was associated with low grade (p < 0.001), small size (p = 0.007),
      oestrogen receptor (ER) positive (p = 0.01), low Ki-67 (p = 0.02) tumours.
      Patients with tumours expressing HMG-CoAR had a significantly prolonged RFS, even
      when adjusted for established prognostic factors (relative risk [RR] = 0.60, 95%
      confidence interval [CI] 0.40 to 0.92; p = 0.02). In ER-negative tumours,
      however, there was a trend, that was not significantly significant, towards a
      shorter RFS in HMG-CoAR expressing tumours. CONCLUSIONS: HMG-CoAR expression is
      an independent predictor of a prolonged RFS in primary breast cancer. This may,
      however, not be true for ER-negative tumours. Further studies are needed to shed
      light on the value of HMG-CoAR expression as a surrogate marker of response to
      statin treatment, especially with respect to hormone receptor status.

PMID- 18808689
TI  - Corticosteroids reverse cytokine-induced block of survival and differentiation of
      oligodendrocyte progenitor cells from rats.
AB  - BACKGROUND: Periventricular leukomalacia (PVL) is a frequent complication of
      preterm delivery. Proinflammatory cytokines, such as interferon-gamma (IFN-gamma)
      and tumor necrosis factor alpha (TNF-alpha) released from astrocytes and
      microglia activated by infection or ischemia have previously been shown to impair
      survival and maturation of oligodendrocyte progenitors and could thus be
      considered as potential factors contributing to the generation of this disease.
      The first goal of the present study was to investigate whether exposure of
      oligodendrocyte precursors to these cytokines arrests the maturation of ion
      currents in parallel to its effects on myelin proteins and morphological
      maturation. Secondly, in the search for agents, that can protect differentiating
      oligodendrocyte precursor cells from cytokine-induced damage we investigated
      effects of coapplications of corticosteroids with proinflammatory cytokines on
      the subsequent survival and differentiation of oligodendrocyte progenitor cells.
      METHODS: To exclude influences from factors released from other cell types
      purified cultures of oligodendrocyte precursors were exposed to cytokines and/or
      steroids and allowed to differentiate for further 6 days in culture. Changes in
      membrane surface were investigated with capacitance recordings and Scanning Ion
      Conductance Microscopy. Na+- and K+- currents were investigated using whole cell
      patch clamp recordings. The expression of myelin specific proteins was
      investigated using western blots and the precursor cells were identified using
      immunostaining with A2B5 antibodies. RESULTS: Surviving IFN-gamma and TNF-alpha
      treated cells continued to maintain voltage-activated Na+- and K+ currents
      characteristic for the immature cells after 6 days in differentiation medium.
      Corticosterone, dihydrocorticosterone and, most prominently dexamethasone,
      counteracted the deleterious effects of IFN-gamma and TNF-alpha on cell survival,
      A2B5-immunostaining and expression of myelin basic protein. The most potent
      corticosteroid tested, dexamethasone, was shown to counteract cytokine effects on
      membrane surface extension and capacitance. Furthermore, coapplication of
      dexamethasone blocked the cytokine-induced downregulation of the inwardly
      rectifying potassium current in 80% of the precursor cells and restored the
      cytokine-blocked down-regulation of the voltage activated Na+- and K+ currents
      during subsequent differentiation. CONCLUSION: Our results show that treatment of
      oligodendrocyte precursors with the inflammatory cytokines TNF-alpha and IFN
      gamma block the differentiation of oligodendrocyte precursors at the level of the
      differentiation of the voltage-gated ion currents. Co-treatment with
      corticosteroids at the time of cytokine application restores to a considerable
      extent survival and differentiation of oligodendrocytes at the level of
      morphological, myelin protein as well as ion current maturation suggesting the
      option for a functional restoration of cytokine-damaged immature
      oligodendrocytes.

PMID- 18808690
TI  - Cell-extracellular matrix interactions regulate neural differentiation of human
      embryonic stem cells.
AB  - BACKGROUND: Interactions of cells with the extracellular matrix (ECM) are
      critical for the establishment and maintenance of stem cell self-renewal and
      differentiation. However, the ECM is a complex mixture of matrix molecules;
      little is known about the role of ECM components in human embryonic stem cell
      (hESC) differentiation into neural progenitors and neurons. RESULTS: A
      reproducible protocol was used to generate highly homogenous neural progenitors
      or a mixed population of neural progenitors and neurons from hESCs. This defined
      adherent culture system allowed us to examine the effect of ECM molecules on
      neural differentiation of hESCs. hESC-derived differentiating embryoid bodies
      were plated on Poly-D-Lysine (PDL), PDL/fibronectin, PDL/laminin, type I collagen
      and Matrigel, and cultured in neural differentiation medium. We found that the
      five substrates instructed neural progenitors followed by neuronal
      differentiation to differing degrees. Glia did not appear until 4 weeks later.
      Neural progenitor and neuronal generation and neurite outgrowth were
      significantly greater on laminin and laminin-rich Matrigel substrates than on
      other 3 substrates. Laminin stimulated hESC-derived neural progenitor expansion
      and neurite outgrowth in a dose-dependent manner. The laminin-induced neural
      progenitor expansion was partially blocked by the antibody against integrin
      alpha6 or beta1 subunit. CONCLUSION: We defined laminin as a key ECM molecule to
      enhance neural progenitor generation, expansion and differentiation into neurons
      from hESCs. The cell-laminin interactions involve alpha6beta1 integrin receptors
      implicating a possible role of laminin/alpha6beta1 integrin signaling in directed
      neural differentiation of hESCs. Since laminin acts in concert with other ECM
      molecules in vivo, evaluating cellular responses to the composition of the ECM is
      essential to clarify further the role of cell-matrix interactions in neural
      derivation of hESCs.

PMID- 18808691
TI  - Evaluation of an immunomagnetic separation method to capture Candida yeasts cells
      in blood.
AB  - BACKGROUND: Candida species have become the fourth most-frequent cause of
      nosocomial bloodstream infections in immunocompromised patients. Therefore, rapid
      identification of pathogenic fungi to species level has been considered critical
      for treatment. Conventional diagnostic procedures such as blood culture or
      biochemical tests are lacking both sensitivity and species specificity, so
      development of rapid diagnostic is essential. RESULTS: An immunomagnetic method
      involving anti-Candida monoclonal antibodies was developed to capture and
      concentrate in human blood four different species of Candida cells responsible
      for invasive yeast infections. In comparison with an automated blood culture,
      processing time of immunomagnetic separation is shorter, saving at least 24 hours
      to obtain colonies before identification. CONCLUSION: Thus, this easy to use
      method provides a promising basis for concentrating all Candida species in blood
      to improve sensitivity before identification.

PMID- 18808692
TI  - Influence of systemic fluoroquinolone administration on the presence of
      Pasteurella multocida in the upper respiratory tract of clinically healthy
      calves.
AB  - The influence of enrofloxacin administration (5 mg/kg) for five consecutive days
      on the occurrence of Pasteurella multocida in the upper respiratory tract of two
      healthy calves was monitored over a 10-day period. From nasal swabs of two
      additional healthy control calves, which received a placebo saline
      administration, P. multocida was isolated throughout the study period. In the
      enrofloxacin treated calves, P. multocida was not demonstrated in the nasopharynx
      from 48 h after the first injection until two days after the last administration,
      when P. multocida reappeared and proved to be clonal in nature to the original
      isolates. During the experiment, no change in minimal inhibitory concentration
      for enrofloxacin of the P. multocida isolates was detected (MIC < or = 0.015
      microg/mL). Enrofloxacin concentrations were determined in the plasma by a high
      performance liquid chromatography method with fluorescence detection. The PK/PD
      indices AUC/MIC and Cmax/MIC ratio were calculated and found to be 1157.7 and
      129.8, respectively. Remarkably, the respiratory pathogen Arcanobacterium
      pyogenes became the predominant recovered organism in the nasopharynx of one
      animal following enrofloxacin therapy throughout the remaining of the experiment.

PMID- 18808693
TI  - Psychometric properties of the Norwegian version of the Safety Attitudes
      Questionnaire (SAQ), Generic version (Short Form 2006).
AB  - BACKGROUND: How to protect patients from harm is a question of universal
      interest. Measuring and improving safety culture in care giving units is an
      important strategy for promoting a safe environment for patients. The Safety
      Attitudes Questionnaire (SAQ) is the only instrument that measures safety culture
      in a way which correlates with patient outcome. We have translated the SAQ to
      Norwegian and validated the translated version. The psychometric properties of
      the translated questionnaire are presented in this article. METHODS: The
      questionnaire was translated with the back translation technique and tested in 47
      clinical units in a Norwegian university hospital. SAQ's (the Generic version
      (Short Form 2006) the version with the two sets of questions on perceptions of
      management: on unit management and on hospital management) were distributed to
      1911 frontline staff. 762 were distributed during unit meetings and 1149 through
      the postal system. Cronbach alphas, item-to-own correlations, and test-retest
      correlations were calculated, and response distribution analysis and confirmatory
      factor analysis were performed, as well as early validity tests. RESULTS: 1306
      staff members completed and returned the questionnaire: a response rate of 68%.
      Questionnaire acceptability was good. The reliability measures were acceptable.
      The factor structure of the responses was tested by confirmatory factor analysis.
      36 items were ascribed to seven underlying factors: Teamwork Climate, Safety
      Climate, Stress Recognition, Perceptions of Hospital Management, Perceptions of
      Unit Management, Working conditions, and Job satisfaction. Goodness-of-Fit
      Indices showed reasonable, but not indisputable, model fit. External validity
      indicators - recognizability of results, correlations with "trigger tool"
      identified adverse events, with patient satisfaction with hospitalization,
      patient reports of possible maltreatment, and patient evaluation of organization
      of hospital work - provided preliminary validation. CONCLUSION: Based on the data
      from Akershus University Hospital, we conclude that the Norwegian translation of
      the SAQ showed satisfactory internal psychometric properties. With data from one
      hospital only, we cannot draw strong conclusions on its external validity.
      Further validation studies linking the SAQ-scores to patient outcome data should
      be performed.

PMID- 18808694
TI  - Bedside rationing by general practitioners: a postal survey in the Danish public
      healthcare system.
AB  - BACKGROUND: It is ethically controversial whether medical doctors are morally
      permitted to ration the care of their patients at the bedside. To explore whether
      general practitioners in fact do ration in this manner we conducted a study
      within primary care in the Danish public healthcare system. The purpose of the
      study was to measure the extent to which general practitioners (GPs) would be
      willing to factor in cost-quality trade-offs when prescribing medicine, and to
      discover whether, and if so to what extent, they believe that patients should be
      informed about this. METHODS: Postal survey of 600 randomly selected Danish GPs,
      of which 330 responded to the questionnaire. The Statistical Package for the
      Social Sciences (SPSS, version 14.0) was used to produce general descriptive
      statistics. Significance was calculated with the McNemar and the chi-square test.
      The main outcome measures of the study were twofold: an assessment of the
      proportion of GPs who, in a mainly hypothetical setting, would consider cost
      quality trade-offs relevant to their clinical decision-making given their
      economic impact on the healthcare system; and a measure of the extent to which
      they would disclose this information to patients. RESULTS: In the hypothetical
      setting 95% of GPs considered cost-quality trade-offs relevant to their clinical
      decision-making given the economic impact of such trade-offs on the healthcare
      system. In all 90% stated that this consideration had been relevant in clinical
      decision-making within the last month. In the hypothetical setting 55% would
      inform their patients that they considered a cost-quality trade-off relevant to
      their clinical decisions given the economic impact of such trade-offs on the
      healthcare system. The most common reason (68%) given for not wanting to inform
      patients about this matter was the belief that the information would not prove
      useful to patients. In the hypothetical setting cost-quality trade-offs were
      considered relevant significantly more often in connection with concerns about
      costs to the patient (86%) than they were in connection with concerns about costs
      to the healthcare system (55%; p < 0.001). CONCLUSION: Although readiness to
      consider cost-quality trade-offs relevant to clinical decisions is prevalent
      among GPs in Denmark, only half of GPs would disclose to patients that they
      consider this relevant to their clinical decision-making. The results of this
      study raise two important ethical problems. First, under Danish law physicians
      are required to inform patients about all equal treatments. The fact that only a
      few GPs would inform their patients about all of the relevant treatments
      therefore seems to contravene Danish law. Second, it is ethically controversial
      that physicians act as economic gatekeepers.

PMID- 18808696
TI  - A study of the distribution and abundance of the adult malaria vector in western
      Kenya highlands.
AB  - BACKGROUND: A sharp rise in the malaria mortality rate has been observed recently
      in western Kenya. Malaria is transmitted by mosquito vectors. Malaria control
      strategies can be more successful if the distribution and abundance of mosquito
      vectors is predicted. However, how mosquito vectors are distributed in space
      remain poor understood, and this question is rarely studied using spatial
      methods. This study aims to provide a better understanding of the distribution
      and abundance of mosquito vectors. To achieve this objective, spatial and non
      spatial methods were employed. The data on the distribution of adult mosquitoes,
      and mosquito breeding habitats in a study area in western Kenya, and
      environmental variables were analyzed. RESULTS: The models developed using
      spatial methods outperformed the models developed using non-spatial methods.
      Houses close to locations where mosquito breeding habitats were repeatedly
      observed had more abundant adult female mosquitoes. Distance to high-order
      streams was identified as an effective predictor for the distribution of adult
      mosquitoes. CONCLUSION: The spatial method is more effective in modeling the
      distribution of adult mosquitoes than the non-spatial method. The results of this
      study can be used to facilitate decision-making related to mosquito surveillance
      and malaria prevention.

PMID- 18808695
TI  - A chemical-genetic strategy reveals distinct temporal requirements for SAD-1
      kinase in neuronal polarization and synapse formation.
AB  - BACKGROUND: Neurons assemble into a functional network through a sequence of
      developmental processes including neuronal polarization and synapse formation. In
      Caenorhabditis elegans, the serine/threonine SAD-1 kinase is essential for proper
      neuronal polarity and synaptic organization. To determine if SAD-1 activity
      regulates the establishment or maintenance of these neuronal structures, we
      examined its temporal requirements using a chemical-genetic method that allows
      for selective and reversible inactivation of its kinase activity in vivo.
      RESULTS: We generated a PP1 analog-sensitive variant of SAD-1. Through temporal
      inhibition of SAD-1 kinase activity we show that its activity is required for the
      establishment of both neuronal polarity and synaptic organization. However, while
      SAD-1 activity is needed strictly when neurons are polarizing, the temporal
      requirement for SAD-1 is less stringent in synaptic organization, which can also
      be re-established during maintenance. CONCLUSION: This study reports the first
      temporal analysis of a neural kinase activity using the chemical-genetic system.
      It reveals that neuronal polarity and synaptic organization have distinct
      temporal requirements for SAD-1.

PMID- 18808697
TI  - Comparison of cardiovascular magnetic resonance of late gadolinium enhancement
      and diastolic wall thickness to predict recovery of left ventricular function
      after coronary artery bypass surgery.
AB  - BACKGROUND: The objective was to compare the value of late gadolinium enhancement
      (LGE) and end-diastolic wall thickness (EDWT) assessed by cardiovascular magnetic
      resonance (CMR) in predicting recovery of left ventricular function after
      coronary artery bypass surgery (CABG). METHODS: We enrolled patients with
      coronary artery disease and left ventricular ejection fraction < 45% who were
      scheduled for CABG. Regional contractility was assessed by cine CMR at baseline
      and 4 months after CABG. EDWT and LGE were assessed at baseline. Predictors for
      improvement of regional contractility were analyzed. RESULTS: We studied 46 men
      and 4 women with an average age of 61 years. Baseline left ventricular ejection
      fraction was 37 +/- 13%. A total of 2,020 myocardial segments were analyzed.
      Abnormal wall motion and the LGE area were detected in 1,446 segments (71.6%) and
      1,196 segments (59.2%) respectively. Wall motion improvement was demonstrated in
      481 of 1,227 segments (39.2%) that initially had wall motion abnormalities at
      baseline. Logistic regression analysis showed that the LGE area, EDWT and resting
      wall motion grade predicted wall motion improvement. Comparison of Receiver
      Operator-Characteristic (ROC) curves demonstrated that the LGE area was the most
      important predictor (p < 0.001). Adding information from LGE to the EDWT can
      decrease the number of false predictions by EDWT alone from 483 to 127 segments.
      CONCLUSION: LGE and EDWT are independent predictors for functional recovery after
      revascularization. However, LGE appears to be a more important factor and
      independent of EDWT.

PMID- 18808698
TI  - Activity of the Bacillus anthracis 20 kDa protective antigen component.
AB  - BACKGROUND: Anthrax is caused by Bacillus anthracis that produce two exotoxins,
      lethal toxin and edema toxin. The lethal toxin is composed of the lethal factor
      (LF) complexed with the cell binding protective antigen (PA83, 83 kDa). Likewise,
      the edema factor (EF) binds to the PA83 to form the edema toxin. Once PA83 is
      bound to the host cell surface, a furin-like protease cleaves the full-length,
      inactive protein into 63 kDa and 20 kDa antigens (PA63 and PA20). PA63 forms a
      heptamer and is internalized via receptor mediated endocytosis forming a protease
      stable pore, which allows EF and LF to enter the cell and exert their toxic
      effects.Both proteolytically cleaved protective antigens (PA63 and PA20
      fragments) are found in the blood of infected animals. The 63 kDa protective
      antigen PA63 fragment has been thoroughly studied while little is known about the
      PA20. METHODS: In this study we examined the role of PA20 using high throughput
      gene expression analysis of human peripheral blood mononuclear cells (PBMC)
      exposed to the PA20. We constructed a PA mutant in which a Factor Xa proteolytic
      recognition site was genetically engineered into the protective antigen PA83 to
      obtain PA20 using limited digestion of this recombinant PA83 with trypsin.
      RESULTS: Global gene expression response studies indicated modulation of various
      immune functions and showed gene patterns indicative of apoptosis via the Fas
      pathway in a subset of the lymphoid cells. This finding was extended to include
      observations of increased Caspase-3 enzymatic activity and the identification of
      increases in the population of apoptotic, but not necrotic cells, based on
      differential staining methods. We identified a list of approximately 40
      inflammatory mediators and heat-shock proteins that were altered similarly upon
      exposure of PBMC to either rPA20 or B. anthracis spores/vegetative cells.
      CONCLUSION: This study shows that the PA20 has an effect on human peripheral
      blood leukocytes and can induce apoptosis in the absence of other PA components.

PMID- 18808699
TI  - Model-driven analysis of experimentally determined growth phenotypes for 465
      yeast gene deletion mutants under 16 different conditions.
AB  - BACKGROUND: Understanding the response of complex biochemical networks to genetic
      perturbations and environmental variability is a fundamental challenge in
      biology. Integration of high-throughput experimental assays and genome-scale
      computational methods is likely to produce insight otherwise unreachable, but
      specific examples of such integration have only begun to be explored. RESULTS: In
      this study, we measured growth phenotypes of 465 Saccharomyces cerevisiae gene
      deletion mutants under 16 metabolically relevant conditions and integrated them
      with the corresponding flux balance model predictions. We first used discordance
      between experimental results and model predictions to guide a stage of
      experimental refinement, which resulted in a significant improvement in the
      quality of the experimental data. Next, we used discordance still present in the
      refined experimental data to assess the reliability of yeast metabolism models
      under different conditions. In addition to estimating predictive capacity based
      on growth phenotypes, we sought to explain these discordances by examining
      predicted flux distributions visualized through a new, freely available platform.
      This analysis led to insight into the glycerol utilization pathway and the
      potential effects of metabolic shortcuts on model results. Finally, we used model
      predictions and experimental data to discriminate between alternative raffinose
      catabolism routes. CONCLUSIONS: Our study demonstrates how a new level of
      integration between high throughput measurements and flux balance model
      predictions can improve understanding of both experimental and computational
      results. The added value of a joint analysis is a more reliable platform for
      specific testing of biological hypotheses, such as the catabolic routes of
      different carbon sources.

PMID- 18808700
TI  - Efficacy of common laboratory disinfectants and heat on killing trypanosomatid
      parasites.
AB  - The disinfectants TriGene, bleach, ethanol and liquid hand soap, and water and
      temperature were tested for their ability to kill bloodstream forms of
      Trypanosoma brucei, epimastigotes of Trypanosoma rangeli and promastigotes of
      Leishmania major. A 5-min exposure to 0.2% TriGene, 0.1% liquid hand soap and
      0.05% bleach (0.05% NaOCl) killed all three trypanosomatids. Ethanol and water
      destroyed the parasites within 5 min at concentrations of 15-17.5% and 80-90%,
      respectively. All three organisms were also killed when treated for 5 min at 50
      degrees C. The results indicate that the disinfectants, water and temperature
      treatment (i.e. autoclaving) are suitable laboratory hygiene measures against
      trypanosomatid parasites.

PMID- 18808701
TI  - In the shadow of the welfare society ill-health and symptoms, psychological
      exposure and lifestyle habits among social security recipients: a national survey
      study.
AB  - BACKGROUND: In Sweden social security is a means-tested financial allowance. The
      Social Services Act states that an individual is entitled to financial support
      when his/her needs are not met in any other way. The aim of the present study was
      to analyse the prevalence and impact of various illness factors and symptoms in
      social security recipients compared to non-recipients in a welfare state, in this
      case Sweden. METHODS: A simple random sample of 20 100 individuals was selected
      from a national survey that covered all individuals in the 18-84 year age group
      in Sweden. A postal survey was thereafter conducted. Multiple logistic regression
      was employed as a statistical test. Odds ratio (OR) and a 95% confidence interval
      (CI) was used. RESULTS: Social security recipients were found to have a
      significantly higher risk in most of the studied variables. Reduced psychological
      wellbeing measured by means of the GHQ12 was significantly higher in this group
      compared to the rest of the population (OR 1.41 CI 1.03-1.94) and their lack of
      trust was greater (OR 1.96, CI 1.45-2.66). They reported more sleep disturbances
      (OR 2.16, CI 1.58-2.94) and suffered from anxiety (OR 1.74, CI 1.28-2.36). Their
      dental health was worse (OR 2.44, CI 1.82-3.28) and they had more pain in their
      hands and legs (OR 1.57, CI 1.16-2.12). Social security recipients were more
      often humiliated (OR 1.79, CI 1.31-2.44) and exposed to threat (OR 1.69, CI 1.09
      2.61). They were less physically active (OR 1.56, CI 1.17-2.08), had a poorer
      diet (OR 1.95, CI 1.45-2.63) and were more often smokers (OR 3.20, CI 2.37-4.33).
      IMPLICATION: The challenge for the welfare state consists of recognising the
      significance of both structural and lifestyle factors as a means of reducing the
      health gap.

PMID- 18808702
TI  - Origin of structural difference in metabolic networks with respect to
      temperature.
AB  - BACKGROUND: Metabolism is believed to adaptively shape-shift with changing
      environment. In recent years, a structural difference with respect to
      temperature, which is an environmental factor, has been revealed in metabolic
      networks, implying that metabolic networks transit with temperature.
      Subsequently, elucidatation of the origin of these structural differences due to
      temperature is important for understanding the evolution of life. However, the
      origin has yet to be clarified due to the complexity of metabolic networks.
      RESULTS: Consequently, we propose a simple model with a few parameters to explain
      the transitions. We first present mathematical solutions of this model using mean
      field approximation, and demonstrate that this model can reproduce structural
      properties, such as heterogeneous connectivity and hierarchical modularity, in
      real metabolic networks both qualitatively and quantitatively. We next show that
      the model parameters correlate with optimal growth temperature. In addition, we
      present a relationship between multiple cyclic properties and optimal growth
      temperature in metabolic networks. CONCLUSION: From the proposed model, we find
      that such structural properties are determined by the emergence of a short-cut
      path, which reduces the minimum distance between two nodes on a graph.
      Furthermore, we investigate correlations between model parameters and growth
      temperature; as a result, we find that the emergence of the short-cut path tends
      to be inhibited with increasing temperature. In addition, we also find that the
      short-cut path bypasses a relatively long path at high temperature when the
      emergence of the new path is not inhibited. Even further, additional network
      analysis provides convincing evidence of the reliability of the proposed model
      and its conclusions on the possible origins of differences in metabolic network
      structure.

PMID- 18808703
TI  - Frequencies of polymorphisms associated with BSE resistance differ significantly
      between Bos taurus, Bos indicus, and composite cattle.
AB  - BACKGROUND: Transmissible spongiform encephalopathies (TSEs) are
      neurodegenerative diseases that affect several mammalian species. At least three
      factors related to the host prion protein are known to modulate susceptibility or
      resistance to a TSE: amino acid sequence, atypical number of octapeptide repeats,
      and expression level. These factors have been extensively studied in breeds of
      Bos taurus cattle in relation to classical bovine spongiform encephalopathy
      (BSE). However, little is currently known about these factors in Bos indicus
      purebred or B. indicus x B. taurus composite cattle. The goal of our study was to
      establish the frequency of markers associated with enhanced susceptibility or
      resistance to classical BSE in B. indicus purebred and composite cattle. RESULTS:
      No novel or TSE-associated PRNP-encoded amino acid polymorphisms were observed
      for B. indicus purebred and composite cattle, and all had the typical number of
      octapeptide repeats. However, differences were observed in the frequencies of the
      23-bp and 12-bp insertion/deletion (indel) polymorphisms associated with two
      bovine PRNP transcription regulatory sites. Compared to B. taurus, B. indicus
      purebred and composite cattle had a significantly lower frequency of 23-bp
      insertion alleles and homozygous genotypes. Conversely, B. indicus purebred
      cattle had a significantly higher frequency of 12-bp insertion alleles and
      homozygous genotypes in relation to both B. taurus and composite cattle. The
      origin of these disparities can be attributed to a significantly different
      haplotype structure within each species. CONCLUSION: The frequencies of the 23-bp
      and 12-bp indels were significantly different between B. indicus and B. taurus
      cattle. No other known or potential risk factors were detected for the B. indicus
      purebred and composite cattle. To date, no consensus exists regarding which
      bovine PRNP indel region is more influential with respect to classical BSE.
      Should one particular indel region and associated genotypes prove more
      influential with respect to the incidence of classical BSE, differences regarding
      overall susceptibility and resistance for B. indicus and B. taurus cattle may be
      elucidated.

PMID- 18808704
TI  - Evidence for positive selection acting on microcystin synthetase adenylation
      domains in three cyanobacterial genera.
AB  - BACKGROUND: Cyanobacteria produce a wealth of secondary metabolites, including
      the group of small cyclic heptapeptide hepatotoxins that constitutes the
      microcystin family. The enzyme complex that directs the biosynthesis of
      microcystin is encoded in a single large gene cluster (mcy). mcy genes have a
      widespread distribution among cyanobacteria and are likely to have an ancient
      origin. The notable diversity within some of the Mcy modules is generated through
      various recombination events including horizontal gene transfer. RESULTS: A
      comparative analysis of the adenylation domains from the first module of McyB
      (McyB1) and McyC in the microcystin synthetase complex was performed on a large
      number of microcystin-producing strains from the Anabaena, Microcystis and
      Planktothrix genera. We found no decisive evidence for recombination between
      strains from different genera. However, we detected frequent recombination events
      in the mcyB and mcyC genes between strains within the same genus. Frequent
      interdomain recombination events were also observed between mcyB and mcyC
      sequences in Anabaena and Microcystis. Recombination and mutation rate ratios
      suggest that the diversification of mcyB and mcyC genes is driven by
      recombination events as well as point mutations in all three genera. Sequence
      analysis suggests that generally the adenylation domains of the first domain of
      McyB and McyC are under purifying selection. However, we found clear evidence for
      positive selection acting on a number of amino acid residues within these
      adenylation domains. These include residues important for active site selectivity
      of the adenylation domain, strongly suggesting selection for novel microcystin
      variants. CONCLUSION: We provide the first clear evidence for positive selection
      acting on amino acid residues involved directly in the recognition and activation
      of amino acids incorporated into microcystin, indicating that the microcystin
      complement of a given strain may influence the ability of a particular strain to
      interact with its environment.

PMID- 18808705
TI  - The impact of a minimal smoking cessation intervention for pregnant women and
      their partners on perinatal smoking behaviour in primary health care: a real-life
      controlled study.
AB  - BACKGROUND: There is a demand for strategies to promote smoking cessation in high
      risk populations like smoking pregnant women and their partners. The objectives
      of this study were to investigate parental smoking behaviour during pregnancy
      after introduction of a prenatal, structured, multi-disciplinary smoking
      cessation programme in primary care, and to compare smoking behaviour among
      pregnant women in the city of Trondheim with Bergen and Norway. METHODS:
      Sequential birth cohorts were established to evaluate the intervention programme
      from September 2000 to December 2004 in primary care as a part of the Prevention
      of Allergy among Children in Trondheim study (PACT). The primary outcome
      variables were self reported smoking behaviour at inclusion and six weeks
      postnatal. Data from the Medical Birth Registry of Norway (MBR) were used to
      describe smoking cessation during pregnancy in Trondheim, Bergen and Norway 1999
      2004. RESULTS: Maternal smoking prevalence at inclusion during pregnancy were 5%
      (CI 95% 4-6) in the intervention cohort compared to 7% (CI 95% 6-9), p = 0.03, in
      the control cohort. Of the pre-pregnancy maternal smokers 25% (CI 95% 20-31) and
      32% (CI 95% 26-38), p = 0.17, were still smoking at inclusion in the intervention
      and control cohorts, respectively. Six weeks postnatal 72% (CI 95% 59-83) and 68%
      (CI 95% 57-77), p = 0.34 of the maternal smokers at inclusion still smoked. No
      significant difference in paternal smoking between the cohorts was found after
      the intervention period. Data from the MBR showed a significantly higher
      proportion of women who stopped smoking during pregnancy in Trondheim than in
      Bergen in 2003 and 2004, p = 0.03 and < 0.001, respectively. CONCLUSION: No
      impact on parental smoking behaviour between the cohorts was observed after the
      smoking intervention programme. Of the women who stopped smoking during pregnancy
      most of them stopped smoking before the intervention. However, we observed a
      significantly higher quitting rate in Trondheim than in Bergen in 2003 and 2004
      which may have been facilitated by the supplemental attention on smoking
      behaviour the PACT study initiated.

PMID- 18808706
TI  - Genome sequencing and analysis reveals possible determinants of Staphylococcus
      aureus nasal carriage.
AB  - BACKGROUND: Nasal carriage of Staphylococcus aureus is a major risk factor in
      clinical and community settings due to the range of etiologies caused by the
      organism. We have identified unique immunological and ultrastructural properties
      associated with nasal carriage isolates denoting a role for bacterial factors in
      nasal carriage. However, despite extensive molecular level characterizations by
      several groups suggesting factors necessary for colonization on nasal epithelium,
      genetic determinants of nasal carriage are unknown. Herein, we have set a genomic
      foundation for unraveling the bacterial determinants of nasal carriage in S.
      aureus. RESULTS: MLST analysis revealed no lineage specific differences between
      carrier and non-carrier strains suggesting a role for mobile genetic elements. We
      completely sequenced a model carrier isolate (D30) and a model non-carrier strain
      (930918-3) to identify differential gene content. Comparison revealed the
      presence of 84 genes unique to the carrier strain and strongly suggests a role
      for Type VII secretion systems in nasal carriage. These genes, along with a
      putative pathogenicity island (SaPIBov) present uniquely in the carrier strains
      are likely important in affecting carriage. Further, PCR-based genotyping of
      other clinical isolates for a specific subset of these 84 genes raise the
      possibility of nasal carriage being caused by multiple gene sets. CONCLUSION: Our
      data suggest that carriage is likely a heterogeneic phenotypic trait and implies
      a role for nucleotide level polymorphism in carriage. Complete genome level
      analyses of multiple carriage strains of S. aureus will be important in
      clarifying molecular determinants of S. aureus nasal carriage.

PMID- 18808707
TI  - Combining classifiers for improved classification of proteins from sequence or
      structure.
AB  - BACKGROUND: Predicting a protein's structural or functional class from its amino
      acid sequence or structure is a fundamental problem in computational biology.
      Recently, there has been considerable interest in using discriminative learning
      algorithms, in particular support vector machines (SVMs), for classification of
      proteins. However, because sufficiently many positive examples are required to
      train such classifiers, all SVM-based methods are hampered by limited coverage.
      RESULTS: In this study, we develop a hybrid machine learning approach for
      classifying proteins, and we apply the method to the problem of assigning
      proteins to structural categories based on their sequences or their 3D
      structures. The method combines a full-coverage but lower accuracy nearest
      neighbor method with higher accuracy but reduced coverage multiclass SVMs to
      produce a full coverage classifier with overall improved accuracy. The hybrid
      approach is based on the simple idea of "punting" from one method to another
      using a learned threshold. CONCLUSION: In cross-validated experiments on the SCOP
      hierarchy, the hybrid methods consistently outperform the individual component
      methods at all levels of coverage. Code and data sets are available at
      http://noble.gs.washington.edu/proj/sabretooth.

PMID- 18808708
TI  - The unresolved safety concerns of bovine thrombin.
AB  - A recent review has suggested that bovine thrombin is not associated with an
      increased risk of bleeding in surgical populations. In spite of extremely limited
      evidence available, many valuable resources (e.g. safety surveillance and post
      marketing programs, case reports) were excluded in reaching this conclusion.
      While waiting for the adequately powered, controlled clinical trials to address
      the effects of bovine thrombin on bleeding and thrombotic events, the potential
      risk cannot be simply ignored. Rather, continued vigilance in the post-surgical
      setting for bleeding events that may be associated with the development of
      acquired coagulation factor inhibitors following bovine thrombin administration
      is warranted.

PMID- 18808709
TI  - Evidence, theory and context: using intervention mapping to develop a worksite
      physical activity intervention.
AB  - BACKGROUND: The workplace is an ideal setting for health promotion. Helping
      employees to be more physically active can not only improve their physical and
      mental health, but can also have economic benefits such as reduced sickness
      absence. The current paper describes the development of a three month theory
      based intervention that aims to increase levels of moderate intensity physical
      activity amongst employees in sedentary occupations. METHODS: The intervention
      was developed using an intervention mapping protocol. The intervention was also
      informed by previous literature, qualitative focus groups, an expert steering
      group, and feedback from key contacts within a range of organisations. RESULTS:
      The intervention was designed to target awareness (e.g. provision of
      information), motivation (e.g. goal setting, social support) and environment
      (e.g. management support) and to address behavioural (e.g. increasing moderate
      physical activity in work) and interpersonal outcomes (e.g. encourage colleagues
      to be more physically active). The intervention can be implemented by local
      facilitators without the requirement for a large investment of resources. A
      facilitator manual was developed which listed step by step instructions on how to
      implement each component along with a suggested timetable. CONCLUSION: Although
      time consuming, intervention mapping was found to be a useful tool for developing
      a theory based intervention. The length of this process has implications for the
      way in which funding bodies allow for the development of interventions as part of
      their funding policy. The intervention will be evaluated in a cluster randomised
      trial involving 1350 employees from 5 different organisations, results available
      September 2009.

PMID- 18808710
TI  - Accelerated evolutionary rates in tropical and oceanic parmelioid lichens
      (Ascomycota).
AB  - BACKGROUND: The rate of nucleotide substitutions is not constant across the Tree
      of Life, and departures from a molecular clock have been commonly reported.
      Within parmelioid lichens, the largest group of macrolichens, large discrepancies
      in branch lengths between clades were found in previous studies. Using an
      extended taxon sampling, we test for presence of significant rate discrepancies
      within and between these clades and test our a priori hypothesis that such rate
      discrepancies may be explained by shifts in moisture regime or other
      environmental conditions. RESULTS: In this paper, the first statistical evidence
      for accelerated evolutionary rate in lichenized ascomycetes is presented. Our
      results give clear evidence for a faster rate of evolution in two Hypotrachyna
      clades that includes species occurring in tropical and oceanic habitats in
      comparison with clades consisting of species occurring in semi-arid and temperate
      habitats. Further we explore potential links between evolutionary rates and
      shifts in habitat by comparing alternative Ornstein-Uhlenbeck models. CONCLUSION:
      Although there was only weak support for a shift at the base of a second tropical
      clade, where the observed nucleotide substitution rate is high, overall support
      for a shift in environmental conditions at cladogenesis is very strong. This
      suggests that speciation in some lichen clades has proceeded by dispersal into a
      novel environment, followed by radiation within that environment. We found
      moderate support for a shift in moisture regime at the base of one tropical clade
      and a clade occurring in semi-arid regions and a shift in minimum temperature at
      the base of a boreal-temperate clade.

PMID- 18808711
TI  - Augmentation of Pulmonary Epithelial Cell IL-8 Expression and Permeability by Pre
      B-cell Colony Enhancing Factor.
AB  - BACKGROUND: Previous studies in our lab have identified Pre-B-cell colony
      enhancing factor (PBEF) as a novel biomarker in acute lung injury (ALI). The
      molecular mechanism of PBEF involvement in the pathogenesis of ALI is still
      incompletely understood. This study examined the role of PBEF in regulating
      pulmonary alveolar epithelial cell IL-8 expression and permeability. METHODS:
      Human pulmonary alveolar epithelial cells (cell line and primary cells) were
      transfected with human PBEF cDNA or PBEF siRNA and then cultured in the presence
      or absence of TNFalpha. PBEF and IL-8 expression were analyzed by RT-PCR and
      Western blotting. In addition, changes in pulmonary alveolar epithelial and
      artery endothelial cell barrier regulation with altered PBEF expression was
      evaluated by an in vitro cell permeability assay. RESULTS: Our results
      demonstrated that, in human pulmonary alveolar epithelial cells, the
      overexpression of PBEF significantly augmented basal and TNFalpha-stimulated IL-8
      secretion by more than 5 to 10-fold and increased cell permeability by >30%; the
      knockdown of PBEF expression with siRNA significantly inhibited basal and
      TNFalpha-stimulated IL-8 secretion by 70% and IL-8 mRNA levels by 74%. Further,
      the knockdown of PBEF expression also significantly attenuated TNFalpha-induced
      cell permeability by 43%. Similar result was observed in human pulmonary artery
      endothelial cells. CONCLUSION: These results suggest that PBEF may play a vital
      role in basal and TNFalpha-mediated pulmonary inflammation and pulmonary
      epithelial barrier dysfunction via its regulation of other inflammatory cytokines
      such as IL-8, which could in part explain the role of PBEF in the susceptibility
      and pathogenesis of ALI. These results lend further support to the potential of
      PBEF to serve as a diagnostic and therapeutic target to ALI.

PMID- 18808712
TI  - The Nigerian national blindness and visual impairment survey: Rationale,
      objectives and detailed methodology.
AB  - BACKGROUND: Despite having the largest population in Africa, Nigeria has no
      accurate population based data to plan and evaluate eye care services. A national
      survey was undertaken to estimate the prevalence and determine the major causes
      of blindness and low vision. This paper presents the detailed methodology used
      during the survey. METHODS: A nationally representative sample of persons aged 40
      years and above was selected. Children aged 10-15 years and individuals aged <10
      or 16-39 years with visual impairment were also included if they lived in
      households with an eligible adult. All participants had their height, weight, and
      blood pressure measured followed by assessment of presenting visual acuity,
      refractokeratomery, A-scan ultrasonography, visual fields and best corrected
      visual acuity. Anterior and posterior segments of each eye were examined with a
      torch and direct ophthalmoscope. Participants with visual acuity of < = 6/12 in
      one or both eyes underwent detailed examination including applanation tonometry,
      dilated slit lamp biomicroscopy, lens grading and fundus photography. All those
      who had undergone cataract surgery were refracted and best corrected vision
      recorded. Causes of visual impairment by eye and for the individual were
      determined using a clinical algorithm recommended by the World Health
      Organization. In addition, 1 in 7 adults also underwent a complete work up as
      described for those with vision < = 6/12 for constructing a normative data base
      for Nigerians. DISCUSSION: The field work for the study was completed in 30
      months over the period 2005-2007 and covered 305 clusters across the entire
      country. Concurrently persons 40+ years were examined to form a normative data
      base. Analysis of the data is currently underway. CONCLUSION: The methodology
      used was robust and adequate to provide estimates on the prevalence and causes of
      blindness in Nigeria. The survey would also provide information on barriers to
      accessing services, quality of life of visually impaired individuals and also
      provide normative data for Nigerian eyes.

PMID- 18808713
TI  - Cortical and subcortical anatomy of chronic spatial neglect following vascular
      damage.
AB  - BACKGROUND: The role of the inferior parietal lobule (IPL) and superior temporal
      gyrus (STG) or subcortical pathways as possible anatomical correlates of spatial
      neglect is currently intensely discussed. Some of the conflicting results might
      have arisen because patients were examined in the acute stage of disease.
      METHODS: We examined the anatomical basis of spatial neglect in a sample of
      patients examined in the post-acute stage following right-hemispheric vascular
      brain damage. Lesions of 28 patients with chronic spatial neglect were contrasted
      to lesions of 22 control patients without neglect using lesion subtraction
      techniques and voxel-wise comparisons. RESULTS: The comparisons identified the
      temporo-parietal junction (TPJ) with underlying white matter, the supramarginal
      gyrus, the posterior STG, and the insula as brain regions damaged significantly
      more often in neglect compared to non-neglect patients. In a subgroup of neglect
      patients showing particularly large cancellation bias together with small errors
      on line bisection damage was prevalent deep in the frontal lobe while damage of
      patients with the reverse pattern was located in the white matter of the TPJ.
      CONCLUSION: Considering our results and the findings of previous studies, spatial
      neglect appears to be associated with a network of regions involving the TPJ,
      inferior IPL, posterior STG, the insular cortex, and posterior-frontal
      projections. Frontal structures or projections may be of particular relevance for
      spatial exploration, while the IPL may be important for object-based attention as
      required for line bisection.

PMID- 18808714
TI  - R/parallel--speeding up bioinformatics analysis with R.
AB  - BACKGROUND: R is the preferred tool for statistical analysis of many
      bioinformaticians due in part to the increasing number of freely available
      analytical methods. Such methods can be quickly reused and adapted to each
      particular experiment. However, in experiments where large amounts of data are
      generated, for example using high-throughput screening devices, the processing
      time required to analyze data is often quite long. A solution to reduce the
      processing time is the use of parallel computing technologies. Because R does not
      support parallel computations, several tools have been developed to enable such
      technologies. However, these tools require multiple modications to the way R
      programs are usually written or run. Although these tools can finally speed up
      the calculations, the time, skills and additional resources required to use them
      are an obstacle for most bioinformaticians. RESULTS: We have designed and
      implemented an R add-on package, R/parallel, that extends R by adding user
      friendly parallel computing capabilities. With R/parallel any bioinformatician
      can now easily automate the parallel execution of loops and benefit from the
      multicore processor power of today's desktop computers. Using a single and simple
      function, R/parallel can be integrated directly with other existing R packages.
      With no need to change the implemented algorithms, the processing time can be
      approximately reduced N-fold, N being the number of available processor cores.
      CONCLUSION: R/parallel saves bioinformaticians time in their daily tasks of
      analyzing experimental data. It achieves this objective on two fronts: first, by
      reducing development time of parallel programs by avoiding reimplementation of
      existing methods and second, by reducing processing time by speeding up
      computations on current desktop computers. Future work is focused on extending
      the envelope of R/parallel by interconnecting and aggregating the power of
      several computers, both existing office computers and computing clusters.

PMID- 18808715
TI  - Diversity of the gut microbiota and eczema in early life.
AB  - BACKGROUND: A modest number of prospective studies of the composition of the
      intestinal microbiota and eczema in early life have yielded conflicting results.
      OBJECTIVE: To examine the relationship between the bacterial diversity of the gut
      and the development of eczema in early life by methods other than stool culture.
      METHODS: Fecal samples were collected from 21 infants at 1 and 4 months of life.
      Nine infants were diagnosed with eczema by the age of 6 months (cases) and 12
      infants were not (controls). After conducting denaturating gradient gel
      electrophoresis (DGGE) of stool samples, we compared the microbial diversity of
      cases and controls using the number of electrophoretic bands and the Shannon
      index of diversity (H') as indicators. RESULTS: Control subjects had
      significantly greater fecal microbial diversity than children with eczema at ages
      1 (mean H' for controls = 0.75 vs. 0.53 for cases, P = 0.01) and 4 months (mean
      H' for controls = 0.92 vs. 0.59 for cases, P = 0.02). The increase in diversity
      from 1 to 4 months of age was significant in controls (P = 0.04) but not in
      children who developed eczema by 6 months of age (P = 0.32). CONCLUSION: Our
      findings suggest that reduced microbial diversity is associated with the
      development of eczema in early life.

PMID- 18808716
TI  - Relation between nodule size and 18F-FDG-PET SUV for malignant and benign
      pulmonary nodules.
AB  - The most common semiquantitative method of evaluation of pulmonary lesions using
      18F-FDG PET is FDG standardized uptake value (SUV). An SUV cutoff of 2.5 or
      greater has been used to differentiate between benign and malignant nodules. The
      goal of our study was to investigate the correlation between the size of
      pulmonary nodules and the SUV for benign as well as for malignant nodules.
      METHODS: Retrospectively, 173 patients were selected from 420 referrals for
      evaluation of pulmonary lesions. All patients selected had a positive CT and PET
      scans and histopathology biopsy. A linear regression equation was fitted to a
      scatter plot of size and SUVmax for malignant and benign nodules together. A dot
      diagram was created to calculate the sensitivity, specificity, and accuracy using
      an SUVmax cutoff of 2.5. RESULTS: The linear regression equations and (R2)s as
      well as the trendlines for malignant and benign nodules demonstrated that the
      slope of the regression line is greater for malignant than for benign nodules.
      Twenty-eight nodules of group one (<or= 1.0 cm) are plotted in a dot diagram
      using an SUVmax cutoff of 2.5. The sensitivity, specificity, and accuracy were
      calculated to be 85%, 36% and 54% respectively. Similarly, sensitivity,
      specificity, and accuracy were calculated for an SUVmax cutoff of 2.5 and found
      to be 91%, 47%, and 79% respectively for group 2 (1.1-2.0 cm); 94%, 23%, and 76%,
      respectively for group 3 (2.1-3.0 cm); and 100%, 17%, and 82%,, respectively for
      group 4 (> 3.0 cm). The previous results of the dot diagram indicating that the
      sensitivity and the accuracy of the test using an SUVmax cutoff of 2.5 are
      increased with an increase in the diameter of pulmonary nodules. CONCLUSION: The
      slope of the regression line is greater for malignant than for benign nodules.
      Although, the SUVmax cutoff of 2.5 is a useful tool in the evaluation of large
      pulmonary nodules (> 1.0 cm), it has no or minimal value in the evaluation of
      small pulmonary nodules (<or= 1.0 cm).

PMID- 18808717
TI  - The stress responsive and morphologically regulated hsp90 gene from
      Paracoccidioides brasiliensis is essential to cell viability.
AB  - BACKGROUND: Paracoccidioides brasiliensis is a dimorphic fungus that causes the
      most prevalent systemic mycosis in Latin America. The response to heat shock is
      involved in pathogenesis, as this pathogen switches from mycelium to yeast forms
      in a temperature dependent fashion that is essential to establish infection.
      HSP90 is a molecular chaperone that helps in the folding and stabilization of
      selected polypeptides. HSP90 family members have been shown to present important
      roles in fungi, especially in the pathogenic species, as an immunodominant
      antigen and also as a potential antifungal therapeutic target. RESULTS: In this
      work, we decided to further study the Pbhsp90 gene, its expression and role in
      cell viability because it plays important roles in fungal physiology and
      pathogenesis. Thus, we have sequenced a Pbhsp90 cDNA and shown that this gene is
      present on the genome as a single copy. We have also confirmed its preferential
      expression in the yeast phase and its overexpression during dimorphic transition
      and oxidative stress. Treatment of the yeast with the specific HSP90 inhibitors
      geldanamycin and radicicol inhibited growth at 2 and 10 microM, respectively.
      CONCLUSION: The data confirm that the Pbhsp90 gene encodes a morphologically
      regulated and stress-responsive protein whose function is essential to cell
      viability of this pathogen. This work also enforces the potential of HSP90 as a
      target for antifungal therapies, since the use of HSP90 inhibitors is lethal to
      the P. brasiliensis yeast cells in a dose-responsive manner.

PMID- 18808718
TI  - Differential SAGE analysis in Arabidopsis uncovers increased transcriptome
      complexity in response to low temperature.
AB  - BACKGROUND: Abiotic stress, including low temperature, limits the productivity
      and geographical distribution of plants, which has led to significant interest in
      understanding the complex processes that allow plants to adapt to such stresses.
      The wide range of physiological, biochemical and molecular changes that occur in
      plants exposed to low temperature require a robust global approach to studying
      the response. We have employed Serial Analysis of Gene Expression (SAGE) to
      uncover changes in the transcriptome of Arabidopsis thaliana over a time course
      of low temperature stress. RESULTS: Five SAGE libraries were generated from A.
      thaliana leaf tissue collected at time points ranging from 30 minutes to one week
      of low temperature treatment (4 degrees C). Over 240,000 high quality SAGE tags,
      corresponding to 16,629 annotated genes, provided a comprehensive survey of
      changes in the transcriptome in response to low temperature, from perception of
      the stress to acquisition of freezing tolerance. Interpretation of these data was
      facilitated by representing the SAGE data by gene identifier, allowing more
      robust statistical analysis, cross-platform comparisons and the identification of
      genes sharing common expression profiles. Simultaneous statistical calculations
      across all five libraries identified 920 low temperature responsive genes, only
      24% of which overlapped with previous global expression analysis performed using
      microarrays, although similar functional categories were affected. Clustering of
      the differentially regulated genes facilitated the identification of novel loci
      correlated with the development of freezing tolerance. Analysis of their promoter
      sequences revealed subsets of genes that were independent of CBF and ABA
      regulation and could provide a mechanism for elucidating complementary signalling
      pathways. The SAGE data emphasised the complexity of the plant response, with
      alternate pre-mRNA processing events increasing at low temperatures and antisense
      transcription being repressed. CONCLUSION: Alternate transcript processing
      appears to play an important role in enhancing the plasticity of the stress
      induced transcriptome. Novel genes and cis-acting sequences have been identified
      as compelling targets to allow manipulation of the plant's ability to protect
      against low temperature stress. The analyses performed provide a contextual
      framework for the interpretation of quantitative sequence tag based transcriptome
      analysis which will prevail with the application of next generation sequencing
      technology.

PMID- 18808719
TI  - The transcription factor ATF3 acts as an oncogene in mouse mammary tumorigenesis.
AB  - BACKGROUND: Overexpression of the bZip transcription factor, ATF3, in basal
      epithelial cells of transgenic mice under the control of the bovine cytokeratin-5
      (CK5) promoter has previously been shown to induce epidermal hyperplasia, hair
      follicle anomalies and neoplastic lesions of the oral mucosa including squamous
      cell carcinomas. CK5 is known to be expressed in myoepithelial cells of the
      mammary gland, suggesting the possibility that transgenic BK5.ATF3 mice may
      exhibit mammary gland phenotypes. METHODS: Mammary glands from nulliparous mice
      in our BK5.ATF3 colony, both non-transgenic and transgenic, were examined for
      anomalies by histopathology and immunohistochemistry. Nulliparous and biparous
      female mice were observed for possible mammary tumor development, and suspicious
      masses were analyzed by histopathology and immunohistochemistry. Human breast
      tumor samples, as well as normal breast tissue, were similarly analyzed for ATF3
      expression. RESULTS: Transgenic BK5.ATF3 mice expressed nuclear ATF3 in the basal
      layer of the mammary ductal epithelium, and often developed squamous metaplastic
      lesions in one or more mammary glands by 25 weeks of age. No progression to
      malignancy was seen in nulliparous BK5.ATF3 or non-transgenic mice held for 16
      months. However, biparous BK5.ATF3 mice developed mammary carcinomas with
      squamous metaplasia between 6 months and one year of age, reaching an incidence
      of 67%. Cytokeratin expression in the tumors was profoundly disturbed, including
      expression of CK5 and CK8 (characteristic of basal and luminal cells,
      respectively) throughout the epithelial component of the tumors, CK6 (potentially
      a stem cell marker), CK10 (a marker of interfollicular epidermal
      differentiation), and mIRSa2 and mIRSa3.1 (markers of the inner root sheath of
      hair follicles). Immunohistochemical studies indicated that a subset of human
      breast tumors exhibit high levels of nuclear ATF3 expression. CONCLUSION:
      Overexpression of ATF3 in CK5-expressing cells of the murine mammary gland
      results in the development of squamous metaplastic lesions in nulliparous
      females, and in mammary tumors in biparous mice, suggesting that ATF3 acts as a
      mammary oncogene. A subset of human breast tumors expresses high levels of ATF3,
      suggesting that ATF3 may play an oncogenic role in human breast tumorigenesis,
      and therefore may be useful as either a biomarker or therapeutic target.

PMID- 18808720
TI  - Comparison of Poisson and Bernoulli spatial cluster analyses of pediatric
      injuries in a fire district.
AB  - BACKGROUND: With limited resources available, injury prevention efforts need to
      be targeted both geographically and to specific populations. As part of a
      pediatric injury prevention project, data was obtained on all pediatric medical
      and injury incidents in a fire district to evaluate geographical clustering of
      pediatric injuries. This will be the first step in attempting to prevent these
      injuries with specific interventions depending on locations and mechanisms.
      RESULTS: There were a total of 4803 incidents involving patients less than 15
      years of age that the fire district responded to during 2001-2005 of which 1997
      were categorized as injuries and 2806 as medical calls. The two cohorts (injured
      versus medical) differed in age distribution (7.7 +/- 4.4 years versus 5.4 +/-
      4.8 years, p < 0.001) and location type of incident (school or church 12% versus
      15%, multifamily residence 22% versus 13%, single family residence 51% versus
      28%, sport, park or recreational facility 3% versus 8%, public building 8% versus
      7%, and street or road 3% versus 30%, respectively, p < 0.001). Using the medical
      incident locations as controls, there was no significant clustering for
      environmental or assault injuries using the Bernoulli method while there were
      four significant clusters for all injury mechanisms combined, 13 clusters for
      motor vehicle collisions, one for falls, and two for pedestrian or bicycle
      injuries. Using the Poisson cluster method on incidence rates by census tract
      identified four clusters for all injuries, three for motor vehicle collisions,
      four for fall injuries, and one each for environmental and assault injuries. The
      two detection methods shared a minority of overlapping geographical clusters.
      CONCLUSION: Significant clustering occurs overall for all injury mechanisms
      combined and for each mechanism depending on the cluster detection method used.
      There was some overlap in geographic clusters identified by both methods. The
      Bernoulli method allows more focused cluster mapping and evaluation since it
      directly uses location data. Once clusters are found, interventions can be
      targeted to specific geographic locations, location types, ages of victims, and
      mechanisms of injury.

PMID- 18808722
TI  - Protective effect of KCNH2 single nucleotide polymorphism K897T in LQTS families
      and identification of novel KCNQ1 and KCNH2 mutations.
AB  - BACKGROUND: KCNQ1 and KCNH2 are the two most common potassium channel genes
      causing long QT syndrome (LQTS), an inherited cardiac arrhythmia featured by QT
      prolongation and increased risks of developing torsade de pointes and sudden
      death. To investigate the disease expressivity, this study aimed to identify
      mutations and common variants that can modify LQTS phenotype. METHODS: In this
      study, a cohort of 112 LQTS families were investigated. Among them two large LQTS
      families linkage analysis with markers spanning known LQTS genes was carried out
      to identify the specific gene for mutational analysis. All exons and exon-intron
      boundaries of KCNH2 and KCNQ1 were sequenced for mutational analysis. RESULTS:
      LQTS-associated mutations were identified in eight of 112 families. Two novel
      mutations, L187P in KCNQ1 and 2020insAG in KCNH2, were identified. Furthermore,
      in another LQTS family we found that KCNH2 mutation A490T co-segregated with a
      common SNP K897T in KCNH2. KCNH2 SNP K897T was reported to exert a modifying
      effect on QTc, but it remains controversial whether it confers a risk or
      protective effect. Notably, we have found that SNP K897T interacts with mutation
      A490T in cis orientation. Seven carriers for A490T and the minor allele T of SNP
      K897T showed shorter QTc and fewer symptoms than carriers with A490T or A490P (P
      < 0.0001). CONCLUSION: Our family-based approach provides support that KCNH2 SNP
      K897T confers a protective effect on LQTS patients. Our study is the first to
      investigate the effect of SNP K897T on another KCNH2 mutation located in cis
      orientation. Together, our results expand the mutational and clinical spectrum of
      LQTS and provide insights into the factors that determine QT prolongation
      associated with increased risk of ventricular tachycardia and sudden death.

PMID- 18808723
TI  - The clinical overlap between functional dyspepsia and irritable bowel syndrome
      based on Rome III criteria.
AB  - BACKGROUND: Epidemiological studies suggest considerable overlap between
      functional dyspepsia (FD) and irritable bowel syndrome (IBS). To date, no surveys
      have been performed to investigate the clinical overlap between these two
      disorders using Rome III criteria. Our aim was to investigate the prevalence and
      risk factors for the overlap of FD and IBS based on Rome III criteria in a large
      clinical sample. METHODS: Consecutive patients at the general gastroenterology
      outpatient clinic were requested to complete a self-report questionnaire. FD and
      IBS were defined by Rome III criteria. RESULTS: Questionnaires were returned by
      3014 patients (52.8% female, 89% response rate). FD-IBS overlap was observed in
      5.0% of the patients, while 15.2% and 10.9% of the patients were classified as FD
      alone and IBS alone, respectively. Compared with non-IBS patients, the odds ratio
      of having FD among IBS patients was 2.09 (95% CI: 1.68-2.59). Patients with FD
      IBS overlap had higher severity scores for the postprandial fullness symptom
      (2.35 +/- 1.49 vs. 1.72 +/- 1.59, P < 0.001) and overall FD symptom (6.65 +/-
      2.88 vs. 5.82 +/- 2.76, P = 0.002) than those with FD alone. The only independent
      risk factor for FD-IBS overlap vs. FD alone was the presence of postprandial
      fullness symptom (OR 2.67, 95% CI: 1.34-5.31). CONCLUSION: Clinical overlap of FD
      and IBS according to Rome III criteria is very common. One risk factor for FD-IBS
      overlap is the presence of postprandial fullness symptom. This study provides
      clues for future pathophysiological studies of FD and IBS.

PMID- 18808724
TI  - Prevalence of distressing symptoms in hospitalised patients on medical wards: A
      cross-sectional study.
AB  - BACKGROUND: Many patients with advanced, serious, non-malignant disease belong to
      the population generally seen on medical wards. However, little research has been
      carried out on palliative care needs in this group. The aims of this study were
      to estimate the prevalence of distressing symptoms in patients hospitalised in a
      Department of Internal Medicine, estimate how many of these patients might be
      regarded as palliative, and describe their main symptoms. METHODS: Cross
      sectional (point prevalence) study. All patients hospitalised in the Departments
      of Internal Medicine, Pulmonary Medicine, and Cardiology were asked to do a
      symptom assessment by use of the Edmonton Symptom Assessment System (ESAS).
      Patients were defined as "palliative" if they had an advanced, serious, chronic
      disease with limited life expectancy and symptom relief as the main goal of
      treatment. RESULTS: 222 patients were registered in all. ESAS was completed for
      160 patients. 79 (35.6%) were defined as palliative and 43 of them completed
      ESAS. The patients in the palliative group were older than the rest, and reported
      more dyspnea (70%) and a greater lack of wellbeing (70%). Other symptoms reported
      by this group were dry mouth (58%), fatigue (56%), depression (41%), anxiety
      (37%), pain at rest (30%), and pain on movement (42%). CONCLUSION: More than one
      third of the patients in a Department of Internal Medicine were defined as
      palliative, and the majority of the patients in this palliative group reported
      severe symptoms. There is a need for skills in symptom control on medical wards.

PMID- 18808725
TI  - Comparison of CT and PET-CT based planning of radiation therapy in locally
      advanced pancreatic carcinoma.
AB  - BACKGROUND: To compare computed tomography (CT) with co-registered positron
      emission tomography-computed tomography (PET-CT) as the basis for delineating
      gross tumor volume (GTV) in unresectable, locally advanced pancreatic carcinoma
      (LAPC). METHODS: Fourteen patients with unresectable LAPC had both CT and PET
      images acquired. For each patient, two three-dimensional conformal plans were
      made using the CT and PET-CT fusion data sets. We analyzed differences in
      treatment plans and doses of radiation to primary tumors and critical organs.
      RESULTS: Changes in GTV delineation were necessary in 5 patients based on PET-CT
      information. In these patients, the average increase in GTV was 29.7%, due to the
      incorporation of additional lymph node metastases and extension of the primary
      tumor beyond that defined by CT. For all patients, the GTVCT versus GTVPET-CT was
      92.5 +/- 32.3 cm3 versus 104.5 +/- 32.6 cm3 (p = 0.009). Toxicity analysis
      revealed no clinically significant differences between two plans with regard to
      doses to critical organs. CONCLUSION: Co-registration of PET and CT information
      in unresectable LAPC may improve the delineation of GTV and theoretically reduce
      the likelihood of geographic misses.

PMID- 18808726
TI  - Tularemia in Germany: the tip of the iceberg?
AB  - Tularemia is a rare, notifiable zoonosis in Germany. Since November 2004, several
      lines of evidence including outbreaks in humans or animals and confirmed
      infections in indigenous hare and rodent populations have indicated a re
      emergence of tularemia in different German federal states. Unfortunately,
      reliable basic information on the seroprevalence in different geographical
      regions, permitting the identification of risk factors, does not exist. Combining
      a sensitive screening assay with a highly specific confirmative immunoblot test,
      we performed a serological investigation on 2416 sera from a population-based,
      cross-sectional health survey of the city population of Leutkirch, Baden
      Wuerttemberg. A total of 56 sera gave positive results indicating a
      seroprevalence of 2.32%. Thus, the seroprevalence is tenfold higher than that
      previously reported in a nationwide study in 2004. Francisella tularensis can
      cause a wide variety of clinical syndromes including severe, sometimes fatal
      disease. Missing epidemiological data on its spatial and temporal distribution in
      an endemic country complicate an appropriate risk assessment necessary for public
      health authorities to be prepared for an adequate outbreak management. This is of
      special concern regarding the extraordinary potential of F. tularensis as an
      agent of bioterrorism. Our investigation performed in a presumed low-risk area
      demonstrated that tularemia might be seriously underestimated in Germany and
      probably in other central European countries as well.

PMID- 18808727
TI  - Spatial and spatio-temporal analysis of Salmonella infection in dairy herds in
      England and Wales.
AB  - Using data from a cohort study conducted by the Veterinary Laboratories Agency
      (VLA), evidence of spatial clustering at distances up to 30 km was found for S.
      Agama and S. Dublin (P values of 0.001) and borderline evidence was found for
      spatial clustering of S. Typhimurium (P=0.077). The evolution of infection status
      of study farms over time was modelled using a Markov Chain model with transition
      probabilities describing changes in status at each of four visits, allowing for
      the effect of sampling visit. The degree of geographical clustering of infection,
      having allowed for temporal effects, was assessed by comparing the residual
      deviance from a model including a measure of recent neighbourhood infection
      levels with one excluding this variable. The number of cases arising within a
      defined distance and time period of an index case was higher than expected. This
      provides evidence for spatial and spatio-temporal clustering, which suggests
      either a contagious process (e.g. through direct or indirect farm-to-farm
      transmission) or geographically localized environmental and/or farm factors which
      increase the risk of infection. The results emphasize the different epidemiology
      of the three Salmonella serovars investigated.

PMID- 18808728
TI  - Extracorporeal oxygenation support for curative surgery in a patient with
      papillary thyroid carcinoma invading the trachea.
AB  - OBJECTIVE: Local extension of thyroid carcinoma can result in massive invasion of
      the trachea, causing severe airway compromise. The pre- and peri-operative
      management of such airway compromise is difficult but critical. We report the use
      of extracorporeal oxygenation support as an alternative peri-operative airway
      management option in such a situation. This approach facilitated curative surgery
      in a patient with papillary thyroid carcinoma invading the trachea. METHOD: We
      present a case report regarding extracorporeal oxygenation support in a patient
      with locally advanced thyroid carcinoma. RESULTS: The patient was a 68-year-old
      woman with aggressive thyroid papillary carcinoma invading the trachea. The
      airway was almost totally obstructed, and tracheal resection and end-to-end
      anastomosis was planned. A venovenous bypass catheter was placed for
      cardiopulmonary bypass, using the bilateral femoral veins. Curative surgery and
      reconstruction were then performed successfully, under general anaesthesia
      assisted by cardiopulmonary bypass oxygenation. CONCLUSION: Cardiopulmonary
      bypass oxygenation is a safe and effective alternative airway management option
      in patients with locally aggressive thyroid cancer.

PMID- 18808729
TI  - Role of sphingosine 1-phosphate receptor expression in eosinophils of patients
      with allergic rhinitis, and effect of topical nasal steroid treatment on this
      receptor expression.
AB  - OBJECTIVE: Recent research has indicated that sphingosine 1-phosphate plays a
      role in allergy. This study examined the effect of allergen challenge on the
      expression of sphingosine 1-phosphate receptors on the eosinophils of allergic
      rhinitis patients, and the effect of steroid treatment on this expression. STUDY
      DESIGN: A prospective, non-randomised study. METHODS: The study had three parts.
      Firstly, sphingosine 1-phosphate receptor expression on the eosinophils of
      allergic rhinitis patients and control patients was determined. Secondly,
      sphingosine 1-phosphate receptor expression was quantified pre- and post-allergen
      challenge, before and after a short course of fluticasone propionate; all
      patients underwent symptom scoring and peak nasal inspiratory flow measurement
      pre- and post-allergen challenge, both before and after steroid or saline
      treatment. Thirdly, the effect of sphingosine 1-phosphate on eosinophil migration
      was examined. RESULTS: The eosinophils of both allergic rhinitis patients and
      controls expressed sphingosine 1-phosphate1, 3, 4, and 5. Eosinophils from all
      allergic rhinitis patients demonstrated up-regulation in sphingosine 1-phosphate
      expression after allergen challenge. These changes were statistically very
      significant for sphingosine 1-phosphate1, 4, and 5, and moderately significant
      for sphingosine 1-phosphate3. Sphingosine 1-phosphate receptor expression up
      regulation was abolished in the steroid-treated group after allergen challenge;
      however, the saline-treated group showed no change in sphingosine 1-phosphate
      receptor expression after allergen challenge. Peak nasal inspiratory flow scores
      were significantly diminished after allergen challenge prior to treatment, but
      not after a course of topical nasal steroids. Sphingosine 1-phosphate induced
      eosinophil chemotaxis was increased following allergen challenge in allergic
      rhinitis subjects. CONCLUSIONS: Local intranasal steroid therapy acts directly to
      block allergen-induced up-regulation of sphingosine 1-phosphate receptors on the
      peripheral eosinophils of allergic rhinitis patients, and this is coincident with
      post-challenge peak nasal inspiratory flow measurement improvements. These
      observations support the idea that such an increase in sphingosine 1-phosphate
      receptor expression is clinically relevant in allergic rhinitis, with potential
      consequences for eosinophil migration and survival.

PMID- 18808730
TI  - Analysis of causes for late presentation of Indian patients with vestibular
      schwannoma.
AB  - OBJECTIVE: To determine the causes of delay in diagnosis and treatment of Indian
      patients with vestibular schwannomas. METHODS: In a prospective study from 2003
      to 2005, 50 patients with a confirmed diagnosis of vestibular schwannoma were
      interviewed to determine the causes for (1) the delay between the patient noting
      the initial symptom and the definitive diagnosis, and (2) the reasons for delayed
      diagnosis. RESULTS: In 90 per cent of patients, the initial symptom was either
      hearing loss (62 per cent), vertigo (24 per cent) or tinnitus (4 per cent).
      However, most patients had been diagnosed and had presented for surgery only
      after neurological symptoms had became apparent. The delay between the initial
      medical consultation and the final diagnosis ranged from one month to 204 months
      (mean +/- standard deviation, 32.2 +/- 38.9 months). After the patient had noted
      symptoms, the diagnosis of vestibular schwannoma was delayed due to doctor
      related causes in 80 per cent of cases, and due to patient-related causes in 20
      per cent. Delay following diagnosis was minimal. CONCLUSIONS: Delay in the
      diagnosis of vestibular schwannoma in Indian patients is due to both doctor- and
      patient-related factors.

PMID- 18808731
TI  - The structure and nature of phonological neighbourhoods in children's early
      lexicons.
AB  - This research examines phonological neighbourhoods in the lexicons of children
      acquiring English. Analyses of neighbourhood densities were done on children's
      earliest words and on a corpus of spontaneous speech, used to measure neighbours
      in the target language. Neighbourhood densities were analyzed for words created
      by changing segments in word-onset position (rhyme neighbours as in pin/bin),
      vowel position (consonant neighbours as in pin/pan/) and word-offset position
      (lead neighbours as in pin/pit). Results indicated that neighbours in children's
      early lexicons are significantly more often distinguished in word-onset position
      (rhyme neighbours) and significantly less often distinguished in word-offset
      position (lead neighbours). Moreover, patterns in child language are more extreme
      than in the target language. Findings are discussed within the PRIMIR framework
      (Processing Rich Information from Multidimensional Interaction Representations;
      Werker & Curtin, 2005). It is argued that early perceptual sensitivity aids
      lexical acquisition, supporting continuity across speech perception and lexical
      acquisition.

PMID- 18808732
TI  - Physician, affective, and cognitive variables differentially predict 'initiation'
      versus 'maintenance' PSA screening profiles in diverse groups of men.
AB  - OBJECTIVES: To evaluate the relevance of demographic, physician, and
      psychological characteristics to PSA screening in ethnic subpopulations and
      ascertain whether the same characteristics distinguish men who have never had a
      PSA from those who screen infrequently and those who screen yearly (adhere).
      DESIGN AND METHODS: Stratified cluster-sampling was used to recruit 533 men (45
      70 years) from four ethnic groups: African-American; European-American; immigrant
      Jamaican; and immigrant men from Trinidad and Tobago. Men provided demographic
      and structural (insurance, regular physician, annual exam, and physician
      recommendation), cognitive (risk and efficacy perceptions, knowledge), and
      emotional variables (cancer worry and embarrassment), and reported on PSA
      screening history. Multinomial logistic regression used these variables to
      predict three screening classifications (never screened, partially adherent, and
      adherent). RESULTS: Multinomial logistic regression showed that minority men were
      less likely to report either never screening or yearly screening, while younger
      men were more likely. Lack of a regular physician (OR=2.87, 95% CI 1.39-5.84), an
      annual exam (OR=1.73, 95% CI 0.91-3.28), and low recommendation (OR=3.76, 95% CI
      2.13-6.66) were associated with being categorized as a never (vs. partially
      adherent) screener, but only annual exam (OR=0.26, 95% CI 0.10-0.63) was
      associated with yearly screening. Lower cancer worry was marginally associated
      with never screening (OR=0.59, 95% CI 0.38-1.04), while knowledge was associated
      with screening yearly over time (OR=0.46, 95% CI 0.28-0.77). CONCLUSIONS:
      Demographic, physician, and psychological variables are differentially associated
      with never, less than yearly, and yearly screening classifications. Minority men
      were unlikely to have never screened, but were also less likely to screen yearly.
      Physician variables were associated with the difference between not screening and
      partially adherent, but not between partially adherent and yearly screening
      suggesting that the role of physicians in PSA behaviour over time would benefit
      from further study.

PMID- 18808733
TI  - Five factor model personality factors moderated the effects of an intervention to
      enhance chronic disease management self-efficacy.
AB  - OBJECTIVES: Peer led interventions can enhance patient self-efficacy for managing
      chronic illnesses, but little is known regarding the moderators or duration of
      their effects. We hypothesized Homing in on Health (HIOH), a variant of the
      Chronic Disease Self-Management Program, would be most effective in patients high
      in neuroticism and low in extraversion, openness, agreeableness, and/or
      conscientiousness. DESIGN: Analysis of data from subjects (N=415) enrolled in an
      ongoing randomized controlled trial. METHODS: Regression analyses were conducted
      to explore whether Five Factor Model (FFM) personality factors moderated the
      effects of HIOH, delivered in subjects' homes or via telephone, on disease
      management self-efficacy. Data were collected at 6 time points over the course of
      1 year. RESULTS: Compared with control and telephone HIOH, home HIOH
      significantly increased self-efficacy, an effect peaking at 6 weeks and fully
      attenuating by 1 year. Moderation analyses revealed the benefit was confined to
      patients higher in neuroticism and/or lower in conscientiousness, agreeableness,
      and extraversion. CONCLUSIONS: A peer led intervention to enhance disease
      management self-efficacy had only short-term effects, and FFM personality factors
      moderated those effects. Measuring personality factors in chronically ill
      individuals may facilitate targeting of self-management interventions to those
      most likely to respond.

PMID- 18808734
TI  - Predicting breakfast consumption: an application of the theory of planned
      behaviour and the investigation of past behaviour and executive function.
AB  - OBJECTIVES: The objective of the current study is to examine the determinants of
      breakfast consumption with the application of the Theory of Planned Behaviour
      (TPB; 1991) and investigate the additional variables of past behaviour and
      executive function. DESIGN: A prospective 1-week study investigating the
      predictive ability of TPB variables, past behaviour and executive function was
      utilized. METHODS: Ninety-six participants were administered two measures of
      executive function (response inhibition and planning) and completed self-report
      questionnaires regarding their attitudes, subjective norms, perceived control,
      intentions and past behaviour of breakfast consumption. One week later,
      participants returned a follow-up questionnaire on their behaviour. RESULTS: The
      result of the study showed that the TPB significantly predicted intentions and
      prospective behaviour of breakfast consumption, however, past behaviour was found
      to be the strongest predictor of future behaviour. Considering executive
      function, response inhibition was not found to predict behaviour, however,
      planning ability explained unique variance in behaviour and moderated the
      association between intention and behaviour. CONCLUSIONS: The findings support
      the use of the TPB in explaining breakfast eating habits, and suggest that
      executive function of planning may be somewhat useful to predict this behaviour.
      The significance of past behaviour also suggests that breakfast consumption may
      commonly be a stable, habitual behaviour that may undermine the need for self
      regulation. Implications for creating behavioural-change interventions are
      discussed.

PMID- 18808735
TI  - In vitro evaluation of the cytotoxicity and genotoxicity of resorcylidene
      aminoguanidine in human diploid cells B-HNF-1.
AB  - RAG belongs to appropriate inhibitors of protein glycation, i.e. formation of
      advanced glycation end products, which are thought to be responsible for some
      complications of DM, including neuropathy, angiopathy, retinopathy and
      nephropathy. In the present study authors have evaluated the genotoxic effect of
      RAG on the cell culture of human neonatal fibroblasts (B-HNF-1) in regard to its
      potential clinical application as inhibitor of advanced glycation end products in
      relationships to the pathogenesis of chronic diabetic complications. The direct
      contact cytotoxicity assay and micronucleus test were performed. The results
      showed that RAG in the concentration range of 1 x 10-4 to 1 x 10-6 mol.l-1 did
      not induce any changes in the morphology of exposed B-HNF-1 cells. The frequency
      of micronuclei was not significantly increased as well. The inhibitive effect of
      resorcylidene aminoguanidine was directly proportional to its concentration. It
      can be concluded that RAG at the selected concentrations has an inhibitive effect
      on proliferation of the treated cells and, at the same time, does not display any
      genotoxic effects on B-HNF-1 cells.

PMID- 18808736
TI  - The lack of correlation between the increased frequency of allele IL-1RN*2 of
      interleukin-1 receptor antagonist gene in Czech patients with knee osteoarthritis
      and the markers of cartilage degradation.
AB  - Primary OA is a common multifactorial disease with not fully clarified molecular
      factors influencing the development of the disease. Among factors disturbing the
      cartilage integrity are cytokines, such as IL-1, which can stimulate proteinases,
      resulting in the cartilage destruction. In this regard, IL-1RA competing with IL
      1 for binding to its receptor may act as an inhibitor of cartilage breakdown.
      Because of the possible functional implications, we tested VNTR polymorphism in
      the second intron of the IL-1RN gene as a putative factor of susceptibility to
      knee OA. Fifty patients with primary knee OA (diagnosed according to ACR
      criteria) and 170 healthy controls were included into the study. PCR using
      primers flanking the VNTR region containing variable numbers of an 86-bp tandem
      repeat was employed to test the hypothesis. An increased frequency and carriage
      rate of the IL-1RN*2 allele was found in OA patients in comparison with controls
      (28 % vs. 15 %, P = 0.0013, OR = 2.97; 95% CI 1.55-5.68 for frequency; 52.5 % vs.
      25.3 %, P = 0.0019, OR = 2.95; 95% CI 1.54-5.68 for carriage rate). In addition,
      a higher frequency of genotype IL-1RN*1/*2 in OA patients was observed as
      compared with controls (42 % vs. 20.6 %, P = 0.0032, OR = 2.79; 95% CI 1.42
      5.48). These results suggest that the IL-1RN*2 allele might represent a factor of
      susceptibility to OA; however, no correlation between this allele and the markers
      of cartilage degradation was found.

PMID- 18808737
TI  - Localization of human coagulation factor VIII (hFVIII) in transgenic rabbit by
      FISH-TSA: identification of transgene copy number and transmission to the next
      generation.
AB  - For chromosomal localization of the hFVIII human transgene in F2 and F3
      generation of transgenic rabbits, FISH-TSA was applied. A short cDNA probe (1250
      bp) targeted chromosomes 3, 7, 8, 9 and 18 of an F2 male (animal 1-3-8). Two
      transgenic offspring (F3) revealed signal positions in chromosome 3 and
      chromosomes 3 and 7, respectively. Sequencing and structure analysis of the
      rabbit orthologous gene revealed high similarity to its human counterpart. Part
      of the sequenced cDNA (1310 bp) served as a probe for FISH-TSA analysis. The
      rabbit gene was localized in the q arm terminus of the X chromosome. This result
      is in agreement with reciprocal chromosome painting between the rabbit and the
      human. The presented FISH-TSA method provides strong signals without any
      interspecies reactivity.

PMID- 18808738
TI  - The late-stage foetal liver microenvironment is essential for later sensitivity
      of B-lymphopoiesis to suppression by oestrogens.
AB  - B-lymphopoiesis in FL differs notably from that of adult B-lymphopoiesis in being
      resistant to suppression by oestrogens due to the lack of expression of oestrogen
      receptors in B-cell progenitors and precursors. We have transplanted middle-stage
      FL cells (E14.5) to adult male mice and demonstrated that B-lymphopoiesis derived
      from FL cells remained resistant to suppression by exogenous oestrogen for
      several months compared to adult BM cells. This significant difference strongly
      suggests that the latestage FL environment exerts an inductive action on the
      haematopoietic stem cells and is mandatory for later sensitivity of B
      lymphopoiesis to suppression by oestrogens. The results also provide the first in
      vivo functional confirmation of a differential responsiveness of FL- and adult BM
      derived B-lymphopoiesis to suppression by oestrogens.

PMID- 18808739
TI  - The RNA content of nucleolar bodies is related to their size - a cytochemical
      study on human monocytes and lymphocytes in blood smears and blood cytospins.
AB  - The present study was undertaken to provide more information on the relationship
      between the nucleolar size and RNA density. Mature monocytes circulating in human
      peripheral blood appeared to be very convenient for such study because they
      contain multiple nucleoli of various sizes in one and the same nucleus. In
      addition, nucleoli without perinucleolar chromatin represented by nucleolar
      bodies are easy to be visualized by a simple cytochemical procedure for RNA
      demonstration. The diameter and density of NoBs in specimens stained for RNA were
      determined by computer-assisted measurements of individual cells. According to
      the results, the nucleolar RNA content was apparently related to the nucleolar
      size because the RNA density of small and large NoBs was practically the same. In
      addition, the diameter measurements also indicated that one or two of several
      NoBs in one nucleus were dominant - larger - than the others. It should also be
      mentioned that the diameter and RNA density of NoBs were studied in monocytes in
      peripheral blood smears regardless of their limited number. Additional study on
      lymphocytes indicated that the preparation procedure of smears modified both
      diameter and density of the measured parameters less than the preparation of
      cytospins as demonstrated by lower variability of the resulting values. Thus, the
      observed differences between smears and cytospins also indicated that the
      specimen preparation procedures should always be considered during evaluation of
      the nucleolar size or staining intensity of nucleoli or cytoplasm due to the
      presence of RNA.

PMID- 18808740
TI  - Determination of angiogenic factors in serum by protein array in patients with
      renal cell carcinoma.
AB  - Using the protein array method we determined the serum levels of a number of
      angiogenic factors. We identified serum levels of angiogenin, PDGF and MCP-1
      (CCL2 chemokine) in serum of 32 patients with RCC, and 14 healthy volunteers by
      means of antibody array analysis. The patients were divided into three groups
      according to their disease stages (I+II, III, and IV). We found significant
      differences between the controls and patients with RCC both pre-operatively and
      post-operatively in angiogenin, PDGF and MCP-1 serum levels. The increase in
      angiogenin, PDGF and MCP-1 lasted in patients with RCC stages I-III even without
      metastases eight weeks post-operatively. The patients with stage IV RCC showed
      disturbed production of PDGF and MCP-1. Protein array analysis is a powerful tool
      for the identification of large numbers of trace proteins. Multiplex antibody
      array is able to provide data more precisely reflecting the nature of
      pathological processes.

PMID- 18808741
TI  - The trials and errors in MS therapy.
AB  - The development programme for novel therapies in multiple sclerosis (MS) has an
      impressive track record which is unique in the field of neurology, and has led to
      the approval of several drugs during the past decade. However, therapeutic
      prosperities face numerous trials that either failed to show efficacy or that had
      to be halted because of other reasons including adverse events. Moreover, certain
      treatment strategies are controversial, both for reasons of practicability and
      for their true clinical benefit. There are serious caveats that highly
      immunoselective approaches such as monoclonal antibodies can only be applied at
      the expense of an increased risk of acute or long-term adverse effects. This
      review focuses on the most important clinical trials on yet unlicensed compounds
      in relapsing-remitting and secondary-progressive MS which failed, were halted or
      are associated with significant adverse effects since 2002. Furthermore, we
      discuss the implications these experiences have for our current view of MS
      pathogenesis as well as future study design. Examples include agents that target
      leukocyte differentiation molecules, co-stimulatory molecules, adhesion molecules
      and chemotaxis, as well as novel immunomodulators and anti-infective therapies.

PMID- 18808742
TI  - Wilhelm Uhthoff: a phenomenon 1853 to 1927.
AB  - The name of Wilhelm Uhthoff is associated with several aspects of progress in
      neurology in the 19th and 20th Century but is best known for his contribution to
      the pathophysiology of transient visual disturbance. Uhthoff was born on 31 July
      1853 in Klein Warin, Germany and died on 21 March 1927 in Breslau, Germany. This
      ophthalmologist described for the first time that increased body temperature from
      physical exertion may lead to transient impairment of vision in patients with
      multiple sclerosis.

PMID- 18808743
TI  - Spotlight on anti-CD25: daclizumab in MS.
AB  - Monoclonal antibodies are a promising new class of therapeutic agents that can be
      employed to target specific molecules of the immune system or any tissue. They
      are currently being tested in a number of clinical trials in autoimmune diseases
      such as multiple sclerosis (MS). One of these, the humanized monoclonal anti-CD25
      antibody daclizumab (Zenapax), is directed against the interleukin-2 (IL-2)
      receptor alpha chain (CD25) that is involved in clonal expansion of autoreactive
      T-cells by binding of its ligand IL- 2. Several years ago daclizumab was approved
      for the prevention of renal allograft rejection. Following promising observations
      in uveitis, daclizumab has since been tested in a number of small clinical trials
      in MS based on the rationale that blocking CD25 would prevent the expansion of
      autoreactive T-lymphocytes. Safety and efficacy data from the preliminary
      clinical exploration as well as findings about the mechanism of action of anti
      CD25 treatment are reviewed here.

PMID- 18808745
TI  - [Treatment of femoral neck fractures in Denmark].

PMID- 18808744
TI  - Detection of anti-aquaporin-4 antibodies in neuromyelitis optica: current status
      of the assays.
AB  - BACKGROUND: Neuromyelitis optica (NMO) is a severe inflammatory demyelinating
      disease that predominantly affects the optic nerve and spinal cord. Since the
      discovery of a specific serum marker for NMO in 2004, and its subsequent
      identification as an antibody to aquaporin-4 (AQP-4), various methods have been
      developed to test for the antibodies in patients sera. OBJECTIVE: To assess the
      principal methods used to measure AQP-4 antibodies in patients sera, describe
      their contribution to neuromyelitis spectrum disease and examine their value in
      the early detection of disease. METHODS: We compared the published data on each
      assay and used the relapsing NMO cohort as a uniform patient group for direct
      assay comparison. RESULTS: The indirect immunofluorescence assay, a cellbased
      assay (CBA) and a fluorescence-based immunoprecipitation assay have broadly
      similar high sensitivities (86%, 91% and 83%) in the relapsing cohort, but the
      indirect immunofluorescence has a lower specificity (91%) compared with the other
      two (both 100% specific). CONCLUSIONS: The indirect immunofluorescence assay for
      NMO-IgG allows the detection of antibodies in routine screening, but the CBA for
      AQP-4 antibodies is the most sensitive. The fluoroimmunoprecipitation assay is a
      potentially high-throughput test for identifying positive sera and for serial
      estimations of antibody levels, but in its present form is slightly less
      sensitive. Overall, these assays are proving very useful in helping to diagnose
      those patients with longitudinally extensive transverse myelitis or recurrent
      optic neuritis who are likely to have relapsing NMO, including patients with
      myelopathy and Sjogrens syndrome, but it appears to be less often positive in
      patients with monophasic NMO.

PMID- 18808746
TI  - [Treatment of intracapsular femoral fractures in Denmark from 1996 to 2007].
AB  - INTRODUCTION: The treatment of medial collum femoris fractures (MCFF) is a topic
      for discussion. Recommendations favour internal fixation at all four levels of
      displacement (Garden type I-IV) for patients younger than 75 years. Older
      patients with undisplaced fractures (Garden type I-II) are being offered internal
      fixation, while arthroplasty is offered to patients with displaced fractures
      (Garden type III-IV). The aim of the present survey is to map the extent and the
      development in the use of the above mentioned methods in Denmark. METHODS: A
      questionnaire was distributed to all 39 emergency wards in Denmark. The results
      were compared with those of a similar survey from 1996. RESULTS: In the period
      1996-2007, the number of wards treating MCFF was reduced by 50%. In 2007 only a
      single mixed surgery ward remained compared with 14 in 1996. Garden type I
      fractures were treated with internal fixation in 77% of the wards and
      conservatively in 8%. In 1996, 60% were offered surgery. Garden type II fractures
      were treated with internal fixation in all wards in 2007 as well as in 1996.
      Garden type III fractures were treated with internal fixation in 12% of the
      wards, while 81% of the wards offered age-graduated treatment. Garden type IV
      fractures were treated with internal fixation in one among 26 wards, 81% performs
      treatment according to the above standards. The period 1996 to 2007 has seen a 12
      13% decrease in the number of patients with displaced MCFF who are offered age
      graduated treatment. CONCLUSION: International recommendations seem to have been
      accepted widely in Danish orthopaedic wards. Nearly all wards currently offer age
      graduated treatment.

PMID- 18808747
TI  - [The immune system and the eye].
AB  - The special relationship between the eye and the immune system rests on a number
      of anatomical, physiological and immunological mechanisms. These mechanisms
      prevent the delicate structures of the eye from potentially damaging immunogenic
      inflammation while protecting against pathogens. Rather than inflammation,
      antigen induces a form of systemic and antigen-specific immunological tolerance.
      Owing to its systemic nature, this tolerance may be utilised to achieve
      successful treatment of immunological disorders.

PMID- 18808748
TI  - [Human serum albumin: gene-technological possibilities].
AB  - Gene technology will soon render it possible to make recombinant human serum
      albumin for clinical use, to produce albumins with altered biological half-lives
      and isoforms with such high and specific binding affinity that they may be used
      as antidotes. Mutants with increased affinity for different cell types can be
      designed and used for drug targeting. Albumin-ligand complexes with new
      properties can be made. The bioavailability of peptide-therapeutics can be
      prolonged by forming albumin fusions. In time, it will probably be possible to
      tailor useful albumins to specific types of patients.

PMID- 18808749
TI  - [Treatment of pilonidal sinus].
AB  - Surgical treatment of pilonidal sinus often leads to significant pain, extended
      period of wound healing and convalescence, and carries a substantial risk of
      recurrence. Based on extant surgical evidence, the present review suggests a
      differential step-up surgical strategy to optimise surgical outcome in the
      treatment of pilonidal sinus.

PMID- 18808750
TI  - [Tumour stem cells in glioma--tomorrow's therapeutic target?].
AB  - Despite intensive research, gliomas still lead to death in most cases. The
      isolation of brain tumour stem cells from gliomas has paved the way for a growing
      body of evidence suggesting that these cells are responsible for the resistance
      of gliomas towards conventional therapy. Recent results suggest that the growth
      of brain tumours can be inhibited by treatment strategies targeting the brain
      tumour stem cells. Here, the brain tumour stem cell paradigm is described with a
      focus on tumour stem cell characteristics and the role of this subpopulation of
      tumour cells in the resistance towards radiation and chemotherapy.

PMID- 18808751
TI  - [Chronic obstructive pulmonary disease and genetics].
AB  - Chronic obstructive pulmonary disease (COPD) is characterised by airflow
      limitation and is associated with an inflammatory response of the lungs primarily
      caused by cigarette smoking. Cigarette smoking is by far the most important
      environmental risk factor for COPD, but less than half of all heavy smokers
      develop COPD. This indicates a genetic contribution to the individual disease
      susceptibility. Although many genes have been examined, the puzzle of COPD
      genetics seems still largely unsolved. It is therefore important to measure
      phenotypes and to perform genome-wide scans of COPD patients in order to unravel
      the contribution of the COPD susceptibility genes.

PMID- 18808752
TI  - [Evaluation of the 360-degree assessment method in a hospital].
AB  - The present study examines the acceptability of the 360-degree assessment method
      as a means for evaluating the management and leadership competencies of the
      clinical staff of a university hospital. Twenty-eight consultants and registered
      nurses underwent evaluation. One group had debriefing with management
      consultants, the other with the head of the clinical department. Two months
      later, the applicability of the method was assessed. The strengths and weaknesses
      of the leaders were exposed, and areas for improvement were made visible, and
      acceptance of the method was widespread. Anonymity was required. The group
      coached by management consultants tended to benefit the most from the evaluation.
      Using a web-based solution to collect the data was unproblematic.

PMID- 18808753
TI  - [Methods in equivalence and non-inferiority trials].
AB  - The randomized clinical trial (RCT) is accepted as the best method for comparing
      therapeutic effects. Most RCTs are superiority trials that aim to show that a new
      therapy is superior to a control therapy. However, some RCTs are equivalence
      trials or non-inferiority trials. Their aim is to show that a new therapy is
      equivalent to or at least not inferior to the control therapy. The various types
      of trials differ significantly in terms of methodology. Few are aware of these
      differences. This paper reviews the methodology of these trials with a particular
      focus on planning, performance, analysis and reporting of the trial.

PMID- 18808754
TI  - [Twin-twin transfusion syndrome in the first trimester].

PMID- 18808755
TI  - [Hydrocephalus as initial presentation of a spinal cord tumour in a child].
AB  - We report a previously healthy two-year-old girl who initially presented with
      signs of increased intracranial pressure of vomiting, lethargy and unstable gait.
      She had communicating hydrocephalus and a ventriculoperitoneal shunt was placed.
      Two years later the girl developed signs of myelopathy and was diagnosed with a
      spinal cord tumour between Th3 and Th9. We suggest that spinal cord tumour should
      be considered in patients with increased intracranial pressure or hydrocephalus
      of unknown origin.

PMID- 18808756
TI  - [Case of severe rhabdomyolosis after protracted overdose of simvastatin].
AB  - The mechanisms of statin-induced muscle injury are not fully understood, and
      early recognition of statin myopathy is critical in order to prevent serious
      sequelae. The case of a 57-year-old woman who had accidentally taken a quadrupled
      dose of simvastatin over a period of 18 days is presented. The patient was
      admitted to hospital with severe rhabdomyolysis and treated with forced diuresis.
      Despite the rhabdomyolysis, the patient's kidney function was not affected, but
      reduced muscle function was observed which was still not fully regained 6 months
      later.

PMID- 18808757
TI  - [Aquagenic pruritus from polycythaemia vera--treatment with paroxetine, a
      selective serotonin reuptake inhibitor].
AB  - Pruritus is one of the most frequent and bothersome symptoms of polycythaemia
      vera and other chronic myeloproliferative disorders. The treatment is often
      difficult and ineffective. Here, we present four patients with severe pruritus,
      three of whom were successfully treated with paroxetin, a selective serotonin
      reuptake inhibitor.

PMID- 18808758
TI  - [Degenerating neurocysticercosis cysts: differential diagnosis with cerebral
      metastasis].
AB  - INTRODUCTION: Neurocysticercosis is the most common parasitic disease of the
      central nervous system. It has a worldwide distribution. CASE REPORT: We report
      the case of a 70-year-old woman from Guadeloupe presenting gait abnormalities,
      impaired ideation, right hemiparesis in a context of weight loss, and fatigue.
      Blood analyses were normal with neither inflammatory syndrome nor blood
      hypereosinophilia. Brain computed tomography and magnetic resonance imaging
      showed hydrocephaly in relation with Sylvius' aqueduc stenosis, and diffuse
      contrast-enhancing lesions suggesting metastases. Because of clinical symptoms,
      the patient underwent ventriculostomy; the cerebral spinal fluid examination was
      normal. Then a frontal biopsy was performed. Histological examination was
      compatible with neurocysticercosis and confirmed by serology. The patient was
      successfully treated with albendazole and steroids. CONCLUSION:
      Neurocysticercosis must be considered as a differential diagnosis of cerebral
      metastasis, especially in patients from endemic countries.

PMID- 18808759
TI  - [Myoclonic astatic seizures in a child with Sturge-Weber syndrome].
AB  - INTRODUCTION: Sturge-Weber syndrome is a neurocutaneous disease associating
      facial and pial angioma. Focal epilepsy is a common sign. In a few cases,
      generalized seizures have been reported. CASE REPORT: We report on a four-year
      old girl with Sturge-Weber syndrome. The first focal seizures occurred at three
      years of age. She developed refractory status epilepticus. At discharge from the
      PICU, she was on a ketogenic diet and received three antiepileptic drugs. No
      seizures were observed for four months. The patient then developed several types
      of seizures: myoclonic seizures, focal clonic seizures, and sudden falls. We were
      unable to determine the etiology of the falls. Typical myoclonic astatic seizures
      were identified on video-electroencephalographic recordings. CONCLUSION: Seizures
      in Sturge-Weber syndrome are usually focal. Four patients with Sturge-Weber
      syndrome and myoclonoastatic seizures are reported in the literature. We discuss
      the pathophysiological mechanisms leading from a focal lesion to generalized
      myoclonoastatic seizures.

PMID- 18808760
TI  - [Sensory-motor neuropathy: a slow and misleading case of leprosy].
AB  - The diagnostic process of sensory-motor neuropathies is difficult. Atypical
      variants and rare etiologies also contribute to delay the diagnosis. We report
      the case of a 70-year-old woman with slowly progressive asymmetric axonal sensory
      motor neuropathy. Leprosy was identified after an eight-year delay. Nerve biopsy
      was required to establish the diagnosis: electron microscopy revealed debris of
      Hansen's bacillus in the nerve. Treatment was fully curative after several
      months. Leprosy is a rare cause of neuropathy in Europeans. Systematic inquiry
      about travel to endemic areas would be helpful in establishing the diagnosis. In
      such cases, nerve biopsy is crucial.

PMID- 18808761
TI  - [Retinal atrophy using optical coherence tomography (OCT) in 15 patients with
      multiple sclerosis and comparison with healthy subjects].
AB  - INTRODUCTION: Multiple sclerosis is a common disabling progressive neurological
      disorder. Axonal loss is thought to be a likely cause of persistent disability
      after a multiple sclerosis relapse. Retinal nerve fiber layer (RNFL) imaging by
      optical coherence tomography (OCT) seems to be a non-invasive way of detecting
      optical axonal loss following optic neuritis. OBJECTIVE: To determine whether
      multiple sclerosis affects retinal nerve fiber layer measurements obtained with
      optical coherence tomography (OCT3-Carl Zeiss Meditec, Dublin, California, USA).
      MATERIAL AND METHODS: Diagnosis of MS was based on the MacDonald criteria. The
      cohort was divided into two groups based on their clinical course (multiple
      sclerosis with [n=8; 16 eyes] or without [n=7; 14 eyes] optic neuritis
      antecedents). The disease-free controls were matched for age and gender (n=15; 30
      eyes). Retinal nerve fiber layer thickness was measured using optical coherence
      tomography (OCT; fastRNFL and RNFL thickness software protocol). Visual acuity,
      visual field, color vision were also noted. RESULTS: There were highly
      significant reductions (p<0.001) of retinal nerve fiber layer thickness in
      affected patients (with or without optic neuritis antecedents) compared with
      control eyes (fastRNFL and RNFL procedures). Visual acuity, visual field and
      color vision were globally less altered than OCT. There were no significant
      relationships among RNFL thickness and visual acuity, visual field, or color
      vision. CONCLUSION: This study has demonstrated the anatomic changes of the
      retinal nerve fiber layer of patients with multiple sclerosis with optic neuritis
      antecedents. Thus axonal loss following optic neuritis can be detected with OCT.
      But the retinal nerve fiber layer of patients without optic neuritis is also
      thinner than disease-free controls so that chronic optic axonal loss can be
      frequent in multiple sclerosis. Additionally, OCT was more sensitive than the
      common ophthalmological explorations to detect optical nerve impairment during
      multiple sclerosis. Finally, we demonstrated that two procedures fastRNFL and
      RNFL could be used to detect optic nerve impairment.

PMID- 18808762
TI  - [Pathophysiology of Huntington's disease: an update].
AB  - Huntington's disease is due to the mutation of the IT15 gene coding for
      Huntingtin protein (Htt). This mutation leads to the expression of an abnormal
      repeat of polyglutamines in the N-terminal region of Htt. The pathophysiology of
      Huntington's disease remains to be elucidated. Various mechanisms have been
      proposed to account for neuronal dysfunction and death, and include both a gain
      of toxic function of the mutated Htt and a loss of function of the wild type Htt.
      Among these mechanisms, transcriptional dysregulation, mitochondrial dysfunction,
      increased excitotoxicity, as well as alteration of neuritic transport and
      synaptic transmission have been proposed. Interestingly, there is a prominent
      vulnerability of the striatal neurons, despite the ubiquitous expression of Htt.
      This may be due to the particular morphological and functional characteristics of
      these neurons, or to their location within the cerebral networks and the inputs
      they receive. As multiple mechanisms are involved in neuronal death, the use of
      drugs association should be considered in future neuroprotective therapeutic
      trials.

PMID- 18808763
TI  - [Parkinson disease and amyotrophic lateral sclerosis. Tauopathies, TDP-43 and SOD
      mutations].
AB  - In addition to a large number of clinical descriptions of atypical cases, recent
      pathological, biochemical and genetic studies challenge the view that amyotrophic
      lateral sclerosis (ALS) is a disorder restricted to the pyramidal motor system.
      Relations between ALS, Parkinson disease, fronto-temporal dementia, progressive
      supranuclear paralysis, and cortico-basal degeneration have now been identified.
      We propose a review of the topic and discuss the contribution of various clinical
      and pathological features leading to consider motoneuron diseases as
      neurodegenerative processes included in a broad spectrum of tauopathies.

PMID- 18808764
TI  - [Ocular disturbances in neuromuscular disorders].
AB  - Compared with other skeletal muscles, extraocular muscles have fundamentally
      distinct properties that make them selectively vulnerable to certain
      neuromuscular disorders. When the oculomotor signs are predominant, their
      temporal progression allows the clinician to make the distinction between a
      muscular disease (mitochondrial disorder, oculopharyngeal muscular dystrophy...)
      and a disorder of the neuromuscular junction (myasthenia gravis, botulism...). In
      other instances, such as myotonic dystrophy or facioscapulohumeral dystrophy, the
      ocular signs are not in the forefront but must be recognized by the
      ophthalmologist as hallmarks of a muscular disorder. In all cases, the
      collaboration between the neurologist and the ophthalmologist is fruitful.

PMID- 18808765
TI  - [Glucose transporter type 1 (GLUT-1) deficiency].
AB  - Impaired glucose transport across the blood brain barrier results in glucose
      transporter type 1 (GLUT-1) deficiency syndrome, first described in 1991. It is
      characterized by infantile seizures refractory to anticonvulsive treatments,
      microcephaly, delays in mental and motor development, spasticity, ataxia,
      dysarthria and other paroxysmal neurologic phenomena, often occurring prior to
      meals. Affected infants are normal at birth following an uneventful pregnancy and
      delivery. Seizures usually begin between the age of one and four months and can
      be preceded by apneic episodes or abnormal eyes movements. Patients with atypical
      presentations such as mental retardation and intermittent ataxia without
      seizures, or movement disorders characterized by choreoathetosis and dystonia,
      have also been described. Glucose is the principal fuel source for the brain and
      GLUT-1 is the only vehicle by which glucose enters the brain. In case of GLUT-1
      deficiency, the risk of clinical manifestations is increased in infancy and
      childhood, when the brain glucose demand is maximal. The hallmark of the disease
      is a low glucose concentration in the cerebrospinal fluid in a presence of
      normoglycemia (cerebrospinal fluid/blood glucose ratio less than 0.4). The GLUT-1
      defect can be confirmed by molecular analysis of the SCL2A1 gene or in
      erythrocytes by glucose uptake studies and GLUT-1 immunoreactivity. Several
      heterozygous mutations, with a majority of de novo mutations, resulting in GLUT-1
      haploinsufficiency, have been described. Cases with an autosomal dominant
      transmission have been established and adults can exhibit symptoms of this
      deficiency. Ketogenic diet is an effective treatment of epileptic manifestations
      as ketone bodies serve as an alternative fuel for the developing brain. However,
      this diet is not effective on cognitive impairment and other treatments are being
      evaluated. The physiopathology of this disorder is partially unclear and its
      understanding could explain the clinical heterogeneity of GLUT-1 deficiency
      patients and lead to new treatments. This probably under-diagnosed deficiency
      should be suspected in children with unexplained neurological disorders including
      epilepsy, mental retardation and movement disorders and confirmed by a lumbar
      puncture and the direct sequencing of GLUT-1.

PMID- 18808766
TI  - Pathology of tumors of the pineal region.
AB  - Tumors of the pineal region are rare and relatively few centers around the world
      have published substantial numbers of carefully studied cases. This review gives
      a historical account of our understanding of the normal pineal and the evolution
      of the classification of tumors and other mass lesions of the pineal region in
      human beings. Based on our experience over the past 30 years, a working
      classification is proposed and recent advances in the neuropathology of these
      lesions are discussed.

PMID- 18808767
TI  - [High prevalence of restless legs syndrome in multiple sclerosis].
AB  - Prevalence of restless legs syndrome (RLS), a clinically defined disorder, varies
      from 2.5 to 15% among populations. In the French adult population, prevalence is
      estimated to be 8.5%. RLS is often secondary to a variety of disorders.
      Neurological conditions usually associated with RLS are neuropathies and
      Parkinson's disease. There are few studies of its association with multiple
      sclerosis (MS). The aim of this study was to estimate RLS prevalence in a
      population of French MS patients. During one month, 17 neurologists from the G
      SEP group prospectively recruited 242 patients who fulfilled the Mc Donald
      criteria for MS. Each patient underwent a standardised questionnaire to verify
      the international criteria of RLS. We collected date of birth, gender, MS course
      (relapsing remitting, primary progressive and secondary progressive) and MS
      duration. Forty-one subjects (18%) met the criteria for RLS. Comparing the RLS
      group with the group without RLS, no significant differences were found in age,
      gender and MS duration. RLS was more prevalent in the relapsing remitting MS
      group. Prevalence of RLS seems to be doubled in MS patients compared to the
      general population. This finding warrants further study. Identification of this
      syndrome in MS patients might lead to specific treatments.

PMID- 18808768
TI  - [CSF biomarkers: proteomics investigations and clinical applications in
      neurodegenerative disorders].
AB  - Given the current developments of therapeutic strategies in the field of
      neurodegenerative disorders, exact diagnosis, especially at an early stage, is
      becoming increasingly crucial for optimal patient care. Importantly, the new
      diagnosis criteria of dementia include functional imagery as well as CSF
      biomarkers. Proteomics investigations of these CSF biomarkers have produced quite
      promising results. The interest of CSF analysis resides in the anatomical and
      pathophysiological characteristics of this fluid. In this article, we will review
      current proteomics investigations of CSF which have led to the discovery and
      validation of biomarkers, mainly in the field of neurodegenerative disorders in
      Alzheimer's disease.

PMID- 18808769
TI  - Modeling the organization of the basal ganglia.
AB  - INTRODUCTION: Several models have been elaborated to describe the structure and
      function of the basal ganglia, but its different levels of architectural
      organization, macroscopic anatomy, connectivity, functional territorial
      subdivision and neuronal morphology have rarely been considered. In this review,
      I present some of these models and I analyze the functioning of the basal ganglia
      at the light of its architectural properties. STATE OF THE ART: The basal ganglia
      form an important neuronal system, which interacts with the cerebral cortex
      through a complex series of loop circuits. While the morphological,
      electrophysiological and biochemical properties of this system are progressively
      known better and better, they have led to various interpretations from which
      different, sometimes contradictory, models have been constructed. The basal
      ganglia are often analyzed as homogeneous nuclei that communicate through
      excitatory or inhibitory connections, the so-called "box and arrows" models.
      Among them, the dual-, triple- and five circuit models are the most popular.
      Analysis of the "inside of the boxes" provides, however, important data such as
      the functional subdivision into three, motor, associative and limbic territories
      and the demonstration that integrative properties are a characteristic of the
      basal ganglia. PERSPECTIVES: Considering these properties, the way cortical
      information is processed in the basal ganglia can be analyzed, which leads to
      modeling its organization and functioning. The striatum receives a compressed
      version of cortical information and transforms it through complex processes of
      activation/deactivation under a double dopaminergic and cholinergic control that
      enables behavioral reinforcement learning. The globus pallidus behaves as a
      keyboard on which various behavioral repertoires can be coded, from the simplest
      movement of a single joint to the most complex motor sequence involving the
      entire body and expressing an emotional content in a cognitive context. The role
      of the subthalamic nucleus must be considered at different scales. At the
      macroscopic scale, it works as a thermostat that regulates the level of execution
      of cortical commands. At a territorial scale, it can process separately motor,
      cognitive and emotional information. At the neuronal scale, it assures a much
      finer neuronal representation of cortical commands and can integrate motor,
      cognitive and emotional aspects. New experiments in both animal models and human
      clinical-research protocols are needed to demonstrate the neuronal mechanisms of
      these processes. CONCLUSION: A model is proposed that considers how neural
      information is processed in the basal ganglia during the execution of motor,
      cognitive and emotional activities.

PMID- 18808770
TI  - [Polyradiculopathy revealing an enteropathy associated T-cell lymphoma in a
      patient with celiac disease].
AB  - INTRODUCTION: Celiac disease (CD) may be complicated by an enteropathy associated
      T-cell lymphoma (EATL), but lymphomatous dissemination outside the
      gastrointestinal tract is uncommon especially to the peripheral nervous sytem.
      OBSERVATION: We report a 54-year-old CD patient with EATL revealed by subacute
      polyradiculopathy. DISCUSSION: Peripheral neuropathies associated with CD are
      generally not polyradiculopathies, but sensorimotor neuropathies. Peripheral
      neurological complications of non-Hodgkin lymphoma are more frequent with B
      lymphoma and a neurological presentation of EATL is very rare. CONCLUSION: This
      case illustrates the usefulness of searching for EATL in CD patients with
      polyradiculopathy.

PMID- 18808771
TI  - Bilateral optic neuropathy revealing Sjogren's syndrome.
AB  - INTRODUCTION: The central nervous system involvement has been reported in 20% of
      cases of primary Sjogren's syndrome (SS), a chronic autoimmune disease
      characterized by a disorder of the exocrine glands secondary to progressive
      lymphocyte infiltration. Classically described neurological manifestations
      include sensorimotor deficits, aseptic meningitis or meningoencephalitis,
      multiple sclerosis-like syndromes and myeolopathies. OBSERVATION: We report here
      the case of a 53-year-old woman who exhibited rapidly progressive visual loss,
      disclosing bilateral optic neuropathy, as an uncommon initial symptom of primary
      SS. Examination of CSF revealed associated aseptic meningitis. Because of the
      lack of efficacy of the first treatment by intravenous corticosteroids, monthly
      intravenous cyclophosphamide was quickly introduced. After six months,
      significant visual recovery was observed. CONCLUSION: Optic neuropathies have
      been rarely reported as the initial symptom revealing primary Sjogren syndrome,
      and bilateral simultaneous lesions remain exceptional.

PMID- 18808772
TI  - [Management and treatment of chronic inflammatory demyelinating
      polyradiculoneuropathy: Results of a French national opinion survey].
AB  - AIM: To assess the clinical and epidemiological characteristics of chronic
      inflammatory demyelinating polyneuropathy (CIDP) in a French population opinion
      survey. METHODS: A national and multicentric metropolitan French opinion survey
      was conducted by TNS Healthcare Sofres from October to December 2006. Five
      thousand and thirty three hospital or private practice physicians were contacted
      by mail. A specific questionnaire (38 questions) was designed for the survey to
      evaluate epidemiology, diagnosis and treatment of CIDP. RESULTS: Four hundred and
      forty one responses were obtained, 430 were analyzed, 11 being excluded. Only 172
      physicians were caring for patients with CIDP, the others feeling that they were
      not competent for this management (only 34% of the physicians cared for at least
      one patient during the study). Treatment was managed by only 28% of the
      physicians and mainly by neurologists working in public hospitals. The percentage
      of treated patients was 84%, the others were not treated because the impairment
      was too mild. IVIg were the first intention treatment for 63.2% of the patients
      and steroids for 30.8% of them. The choice was mainly based on the good tolerance
      profile of IVIg, both treatments being considered as efficacious. CONCLUSION:
      This survey has shown a higher incidence and prevalence of CIDP than expected but
      a methodological bias may have led to an overestimation (a same patient being
      included twice). Treatment complied with recommendations and guidelines while the
      diagnosis may be improved.

PMID- 18808773
TI  - [Congenital insensitivity to pain].
AB  - Congenital insensitivity to pain (CIP) is a rare syndrome with various clinical
      expressions, characterized by a dramatic impairment of pain perception since
      birth. In the 1980s, progress in nerve histopathology allowed to demonstrate that
      CIP was almost always a manifestation of hereditary sensory and autonomic
      neuropathies (HSAN) involving the small-calibre (A-delta and C) nerve fibres
      which normally transmit nociceptive inputs along sensory nerves. Identification
      of the genetic basis of several clinical subtypes has led to a better
      understanding of the mechanisms involved, emphasizing in particular the crucial
      role of nerve growth factor (NGF) in the development and survival of nociceptors.
      Recently, mutations of the gene coding for the sodium channel Nav1.7--a voltage
      dependent sodium channel expressed preferentially on peripheral nociceptors and
      sympathetic ganglia--have been found to be the cause of CIP in patients showing a
      normal nerve biopsy. This radical impairment of nociception mirrors the
      hereditary pain syndromes associated with "gain of function" mutations of the
      same ion channel, such as familial erythromelalgia and paroxysmal extreme pain
      disorder. Future research with CIP patients may identify other proteins
      specifically involved in nociception, which might represent potential targets for
      chronic pain treatment. Moreover, this rare clinical syndrome offers the
      opportunity to address interesting neuropsychological issues, such as the role of
      pain experience in the construction of body image and in the empathic
      representation of others' pain.

PMID- 18808774
TI  - [Can subthalamic nucleus stimulation reveal parkinsonian rest tremor?].
AB  - INTRODUCTION: Rest tremor, one of the main symptoms in Parkinson's disease (PD),
      is dramatically improved following subthalamic nucleus stimulation (STN). Results
      are often better than after l-dopa treatment. The occurrence of rest tremor after
      neurosurgery in patients without preoperative tremor is uncommon. AIM: The aim of
      this work was to investigate the role of subthalamic nucleus stimulation in the
      appearance of parkinsonian rest tremor. PATIENTS-RESULTS: Thirty PD patients
      (14%) out of 215 undergoing STN deep brain stimulation had an akinetorigid form
      of the disease, without preoperative tremor 11 years after onset of the disease.
      Six of them experienced the appearance of tremor six months after bilateral STN
      stimulation when the stimulator was switched off in the Off medication state.
      This de novo parkinsonian tremor was improved by l-dopa treatment and disappeared
      when the stimulator was turned on. CONCLUSION: This finding suggests that
      infraclinical parkinsonian tremor is probably present in all PD patients.

PMID- 18808775
TI  - [Spasmodic laughter syncope. An unusual complication of pseudobulbar palsy].
AB  - INTRODUCTION: Spasmodic laughter is a classical sign of pseudobulbar palsy, but
      it has never been reported, to our knowledge, to provoke syncope. CASE REPORT: A
      63-year-old hypertensive and diabetic man with peripheral neuropathy and lacunar
      pseudobulbar palsy presented with three episodes of spasmodic laughter which had
      induced syncope. No new episode was observed after the beginning of low dose
      bisoprolol. DISCUSSION: Sustained or spasmodic laughter is accompanied by
      repetitive bursts of forced expiration, corresponding to short repetitive
      Valsalva maneuvers. Laughter-induced syncope is considered as one of the many
      Valsalva-type/vagally mediated syncopal attacks leading to rapid fall in blood
      pressure without compensatory tachycardia. The presence of autonomic diabetic
      neuropathy may also contribute to these attacks.

PMID- 18808776
TI  - [Cauda equina syndrome revealing neuroblastoma].
AB  - INTRODUCTION: Neuroblastoma is the most common solid tumor of childhood.
      Neurological involvement is rare resulting from cord or nerve compression. CASE
      REPORT: A 7-year-old child was hospitalized for cauda equina syndrome. MRI showed
      retroperitoneal lesion with dumbbell intradural spreading. Blood and urinary
      catecholamine level were elevated confirming the diagnosis of neuroblastoma. She
      was treated with chemotherapy alone with partial neurological recovery.
      DISCUSSION AND CONCLUSION: Cauda equina compression revealing neuroblastoma is
      exceptional especially at an early phase in the youngest patients. Treatment is
      based on surgical resection and/or chemotherapy and/or radiation therapy. Long
      term prognosis is sometimes poor with neurological sequels.

PMID- 18808777
TI  - [Brucellar meningitis complicated by aneurysmal subarachnoid hemorrhage].
AB  - INTRODUCTION: Brucellosis is a rare disease in which neurological complications,
      and more particularly, intracranial aneurysmal hemorrhages were rarely reported.
      CASE REPORT: A brucellar meningitis was diagnosed in a 29-year-old man, who had
      been suffering from an unusual headache for about two months. Three days after
      beginning treatment, the patient developed an intracranial right frontal
      hemorrhage that led to the discovery of a ruptured anterior communicating artery
      aneurysm. The aneurysm was clipped surgically and doxycycline and rifampin were
      given for three months. The outcome was excellent. DISCUSSION AND CONCLUSION:
      Clinical manifestations of brucellosis are variable. Neurovascular complications
      are rare and probably linked to delay in diagnosis of CNS invasion or inadequate
      initial treatment. Appropriate and prompt medical, and if necessary, surgical
      management can lead to excellent outcome.

PMID- 18808778
TI  - [The effect of age on executive functioning after acquired brain injury in
      adults].
AB  - INTRODUCTION: Executive functioning deficits have often been described in normal
      aging. They are also known to be a frequent sequel of traumatic brain injury,
      where patients may exhibit severe long-standing impairments in instrumental
      activities of daily living. One could therefore expect that cerebral lesions
      affecting executive functioning would result in more severe impairments in older
      patients. We previously developed an ecological assessment of executive
      functions, consisting of a cooking task, requiring multitasking abilities and
      known to be sensitive to a dysexecutive syndrome [Cortex 36 (2000) 649-669]. The
      aim of this study was to analyze the effect of age on the cognitive and
      ecological assessments of executive functions in a group of patients with
      acquired brain injury (ABI) resulting in a dysexecutive syndrome. Studies in this
      area usually focus on patients older than 60 or 65, but we chose to analyze the
      effect of age in a younger population. We hypothesized that older patients would
      have poorer performances on the cognitive and ecological tests of executive
      functioning, when compared to younger patients. METHODS: Forty-five patients with
      ABI resulting in frontal lesions and a dysexecutive syndrome participated in this
      study. Patients underwent a comprehensive battery of cognitive tests assessing
      executive functioning, as well as the cooking task. We also studied a group of 12
      control subjects who performed the cooking task. RESULTS: No effect of age was
      found on performance in the cooking task in the control group. Age was not
      related to demographic parameters or injury severity in the ABI group. Although
      the ABI group was relatively young (mean age: 40.3 years (S.D.=12.5), ranging
      from 17 to 63), results indicated a significant deleterious effect of age on the
      cognitive tests of executive functioning in the ABI group. We also highlighted a
      significant worsening of patients' performance in the cooking task with age, and
      this effect was found on several variables of task analysis: the number of errors
      and occurrence of dangerous behaviors. CONCLUSION: Our study demonstrates the
      deleterious effect of aging on cognitive and ecological assessment of executive
      functioning after ABI. The strength of this study is that it deviated from the
      traditional age considered in studies of elderly populations and focused on
      younger patients. It is therefore important to consider the implication that this
      may have on a patient's rehabilitation program and postinjury discharge.

PMID- 18808779
TI  - [Late cerebellar ataxia associated with fragile X premutation].
AB  - INTRODUCTION: The fragile X-associated tremor/ataxia syndrome (FXTAS) is a
      neurodegenerative disorder that affects carriers, principally males after 50
      years of age, of premutation alleles of the fragile X mental retardation 1 (FMR1)
      gene. Clinical features of FXTAS are an intention tremor and/or a cerebellar
      ataxia, with or without parkinsonism, cognitive disorders, neuropathy and
      autonomic dysfunction. MRI shows symmetrical signal abnormalities in the middle
      cerebellar peduncles and deep cerebellar white matter, typically sparing the
      dentate nucleus, associated with generalized atrophy. We report a case of FXTAS
      with isolated cerebellar ataxia. CASE REPORT: We report the case of a 60-year-old
      right-handed man with an uneventful personal and familial history. Since 2002, he
      progressively developed gait ataxia associated with paresthesia in the lower
      limbs. The physical examination revealed static and kinetic cerebellar ataxia
      with dysarthria. Exhaustive screening tests (inflammatory, immunological,
      metabolic, infectious and neoplasic) and the cerebrospinal fluid analysis were
      normal. The brain MRI T2-weighted sequences showed diffuse increased signal in
      both cerebellar white matter and middle peduncles suggestive of FXTAS. Functional
      explorations (evoked somesthesic and visual potentials, electromyogram, and
      cerebral scintigraphy) confirmed the isolated cerebellar involvement. The FXTAS
      was suggested and the genotype was explored. Southern Blot revealed an expansion
      of trinucleotide CGG with 107 repetitions, confirming the diagnosis of FXTAS.
      DISCUSSION: In patients with a fragile X premutation, FMR1 protein levels are
      gradually reduced with increased repeat number, despite elevated FMR1 transcripts
      levels. Neuropathologic examination reveals eosinophilic intranuclear inclusions
      in neurons and astrocytes throughout the cortex, subcortical regions, and brain
      stem. The pathogenic hypothesis would be related to a gain of function with toxic
      effects of FMR1 messenger RNA on cellular metabolism. Cerebellar ataxia, which
      may be isolated or not, is the most frequent neurologic manifestation, like many
      studies showed. CONCLUSION: FXTAS should be suspected in patients with
      unexplained late-onset cerebellar ataxia. Typical presentation includes a male in
      his fifties with progressive ataxia and tremor. Brain MRI with symmetrical
      cerebellar abnormalities is very suggestive of this diagnosis. Genetic screening
      and advice for the patient and his family must be proposed in order to detect the
      fragile X syndrome.

PMID- 18808780
TI  - [Approaches to segment multiple-sclerosis lesions on conventional brain MRI].
AB  - Different sets of criteria are currently used for the diagnosis of multiple
      sclerosis (MS). Some are based on clinical features, while others are related to
      imaging findings. Among the image processing systems, specific criteria include
      spatial dissemination of lesions in one image or their temporal dissemination in
      images acquired at different time points. In addition, the evolution of the
      lesion load can be used to evaluate treatment efficiency in MS clinical research.
      Consequently, obtaining a precise segmentation of the MS lesion appears to be
      crucial. In the literature, a number of semi-automated or completely automated
      approaches have been proposed enabling a reduction of the inter- and intra-expert
      variability for manual delineations. A comprehensive state-of-the-art
      classification of the most representative systems is presented here.

PMID- 18808781
TI  - [Use of mitoxantrone in early multiple sclerosis with malignant disease course.
      Observational study in 30 patients with clinical and MRI outcomes after one
      year].
AB  - INTRODUCTION: In an observational multicenter study, we analyzed retrospectively
      30 patients with malignant form of multiple sclerosis (MS) treated with
      mitoxantrone the year following the first neurological event. METHODS: The 30
      patients were selected according to Weinshenker criteria of malignant MS (either
      a "catastrophic" relapse or a quickly aggressive form). We compared clinical and
      MRI findings the year before with the year following mitoxantrone onset
      treatment: annualized relapse rates (ARR), EDSS score and percentage of patients
      with gadolinium enhancing lesions on MRI. RESULTS: A total of 87 relapses were
      observed in the 5.7 months before and 10 during the year following onset of
      mitoxantrone treatment. The ARR decreased by 95% (6.0+/-2 before and 0.3+/-0.7
      after). Twenty-four patients (80%) were relapse-free one year after onset of
      mitoxantrone treatment. The EDSS score improved in 87% of MS patients and the
      mean EDSS decreased by 1.9. Ninety-seven percent had at least gadolinium
      enhancing lesions before the start of mitoxantrone treatment as compared to 17%
      after. CONCLUSION: In our experience, mitoxantrone had a rapid and strong impact
      on the malignant forms of MS with a short disease duration. In this MS subgroup,
      mitoxantrone should be considered as an early treatment option.

PMID- 18808782
TI  - [Status epilepticus in the elderly patients. A retrospective study of 63 in
      patients].
AB  - INTRODUCTION: Status epilepticus is quite frequent in the elderly but rarely
      studied despite the poor functional prognosis and significant mortality. METHODS:
      We retrospectively evaluated the clinical manifestations and electroencephalogram
      findings observed over a two-year period in 63 consecutive inpatients aged over
      70 years presenting status epilepticus. The variables studied included age, sex,
      the number of concomitant chronic active diseases, previous neurological
      disorders, brain lesions on CT or MRI, the use and withdrawal of medications and
      outcome. RESULTS: The incidence of status epilepticus was 1%; two-thirds in women
      and one-third in men. The mean age was 83 years. Complex partial status
      epilepticus was noted in 91% with predominant features of confusion (89%),
      impairment of consciousness (75%) or psychiatric symptoms (46%). Etiologies were
      often multifactorial and acute symptomatic. Etiology was metabolic in 60%, drug
      induced in 51%, demential in 44%, cerebrovascular in 37%, infectious in 30% and
      other neurological disorders in 28% of the cases. Antiepileptic drugs used to
      treat status epilepticus were benzodiazepine (60%), often in association with
      lamotrigine (51%), valproate (46%) or phenytoin (25%). Maintenance of an
      antiepileptic drug was found in 70% of cases. Complications were loss of autonomy
      (86%), malnutrition (67%), infections (51%), dementia (30%), pressure sores
      (14%), and recurrent epilepsy (13%). Mortality was 32% of cases and it was higher
      in men. CONCLUSION: These findings have shown some special features of status
      epilepticus among the elderly but other prospective studies are needed to confirm
      these results and to identify optimal management to decrease mortality, and
      improve the poor functional prognosis.

PMID- 18808783
TI  - [Epileptogenic brain malformations: radiological and clinical presentation and
      indications for genetic testing].
AB  - Malformations of cortical development (MCD) represent a major cause of
      developmental disabilities and severe epilepsy. Advances in imaging and genetics
      have improved the diagnosis and classification of these conditions. Up to now,
      eight genes have been involved in different types of MCD. Lissencephaly
      pachygyria and subcortical band heterotopia (SBH) represent a malformative
      spectrum resulting from mutations of either LIS1 or DCX genes. LIS1 mutations
      cause a more severe malformation in the posterior brain regions. DCX mutations
      usually cause anteriorly predominant lissencephaly in males and SBH in female
      patients. Additional forms are X-linked lissencephaly with corpus callosum
      agenesis and ambiguous genitalia associated with mutations of the ARX gene.
      Lissencephaly with cerebellar hypoplasia (LCH) encompass heterogeneous disorders
      named LCH type a to d. LCHa are related with mutation in LIS1 or DCX, LCHb with
      mutation of RELN gene, and LCHd could be related with TUBA1A gene. Polymicrogyria
      encompass a wide range of clinical, aetiological and histological findings. Among
      several syndromes, recessive bilateral fronto-parietal polymicrogyria has been
      associated with mutations of the GPR56 gene. Bilateral perisylvian polymicrogyria
      showed a linkage to chromosome Xq28 in some pedigrees, and mutations in SRPX2
      gene in others conditions. X-linked bilateral periventricular nodular heterotopia
      (BPNH) consists of BPNH with focal epilepsy in females and prenatal lethality in
      males. Filamin A (FLNA) mutations have been reported in some families and in
      sporadic patients. It is possible to infer the most likely causative gene by
      brain imaging studies and other clinical findings. Based on this experience, a
      detailed phenotype analysis is needed to develop the most efficient research on
      MCD in the future.

PMID- 18808784
TI  - [Executive functioning in normal aging].
AB  - INTRODUCTION: Executive impairments seem to be an important characteristic of
      normal cognitive aging. This impairment can however affect elderly individuals in
      their daily living activities. Miyake et al.[Cogn Psychol 41 (2000) 49-100]
      showed that the executive system is made up of three particular components: the
      inhibition of irrelevant information, the updating of information in working
      memory and the mental shifting between tasks or mental sets. Although several
      studies showed specific trends with aging of one of these components, few have
      considered the functional links between the components. The present study
      examined the specific impairments of executive functions which occur in normal
      aging. We intend to characterize more precisely how the three components can
      evolve during the aging process. METHODS: The performances of 30 young adults and
      29 older adults were evaluated on an executive battery of tests [Rev Neuropsychol
      11 (2001) 383-433] and compared. RESULTS: The descriptive analysis of the results
      showed that older participants were impaired in most of the tests compared to
      younger participants. In older participants, the executive functions evaluated
      revealed variable patterns of impairment. There was no set pattern and some tests
      gave the same results for younger and older subjects. Regarding the three
      executive components, inhibition and updating were impaired in older subjects,
      while flexibility was not. CONCLUSIONS: This study provides elements useful for
      better understanding the mechanisms controlling executive function allowing a
      better comprehension of the normal pattern of cognitive aging.

PMID- 18808785
TI  - [McArdle disease (gycogenosis type V): analysis of clinical, biological and
      genetic features of five French patients].
AB  - INTRODUCTION: McArdle disease (glycogenosis type V) is an autosomal recessive
      metabolic myopathy. Defect in glycogen breakdown is due to mutations of the gene
      for myophosphorylase (PYGM). Among patients of the department, we searched for
      correlations between disease phenotype, biochemistry analysis of muscle samples
      and PYGM genotype. METHODS: We included five patients whose muscle biopsy showed
      deposits of glycogen and negative histochemical staining for myophosphorylase.
      RESULTS: All patients exhibited exercise intolerance and high serum CK levels
      (mean 4400). Two of them had an acute renal insufficiency caused by
      rhabdomyolysis. One patient developed moderate late-onset muscle weakness of the
      proximal part of upper limbs. Muscle glycogen concentration was high (three times
      the normal). Myophosphorylase activity was undetectable in four muscle samples
      out of five. Two patients were homozygous and two other heterozygous for the R50X
      mutation of PYGM. The other one had a novel missense mutation S814N. Patients
      homozygous for R50X mutation had higher CK levels (8080 versus 1457, p=0.046),
      but disease severity and muscle glycogen concentrations were equivalent.
      CONCLUSIONS: Our patients had typical clinical and laboratory features of McArdle
      disease. Diagnosis was suggested by exercise intolerance with high CK levels. The
      R50X mutation was the most common (60% of the mutated alleles). We found no
      relationship between clinical severity, PYGM genotype and biochemistry analysis
      of muscle samples.

PMID- 18808786
TI  - [Multiple sclerosis and familial Mediterranean fever: a case report].
AB  - INTRODUCTION: Few cases of patients with both Familial Mediterranean Fever (FMF)
      and Multiple Sclerosis (MS) have been reported, mainly from Turkey. Central
      nervous system manifestations are rare in FMF. CASE REPORT: We report the case of
      a 37-year-old right-handed man with FMF diagnosed at 17 the age of years and
      successfully treated with colchicine. The patient was born in Algeria and lived
      in France since he was four years old. He had a brother who had multiple
      sclerosis. When the patient was 23 years old, he experienced diplopia and leg
      numbness that resolved spontaneously without treatment. Ten years later, new
      neurological events appeared every six months and were treated with corticoid
      steroids. The diagnosis of MS was made. In 2006, he was hospitalized for new
      explorations in order to search for neuro-Behcet's disease, because of the
      development of a canker sore. There was no argument for neuro-Behcet's disease.
      DISCUSSION: Neurological complications of FMF are rare. It is important to rule
      out a neuro-Behcet disease in a FMF patient with neurological disorders. Previous
      studies and case reports on the association between FMF and MS have failed to
      draw a clear conclusion as to whether this is a true association or a simple
      coincidence. In our patient's clinical situation, we found no argument for
      changing the treatment of MS and FMF.

PMID- 18808787
TI  - Foreword.

PMID- 18808788
TI  - Preface.

PMID- 18808789
TI  - Chapter 1 Introduction From bench to bed and back.

PMID- 18808790
TI  - Chapter 2 Nucleus basalis of Meynert (NBM) and diagonal band of Broca (DBB).

PMID- 18808791
TI  - Chapter 3 Islands of Calleja (insulae terminalis).

PMID- 18808792
TI  - Chapter 4 Suprachiasmatic nucleus (SCN) and pineal gland (Fig. 4A).

PMID- 18808793
TI  - Chapter 5 Sexually dimorphic nucleus of the preoptic area (SDN-POA) =
      intermediate nucleus = interstitial nucleus of the anterior hypothalamus (INAH-1)
      = preoptic nucleus.

PMID- 18808794
TI  - Chapter 6 Other sexual dimorphisms.

PMID- 18808795
TI  - Chapter 7 Bed nucleus of the stria terminalis (BST) and the septum.

PMID- 18808797
TI  - Chapter 9 The ventromedial nucleus (VMN; nucleus of Cajal).

PMID- 18808796
TI  - Chapter 8 Supraoptic and paraventricular nucleus (SON, PVN).

PMID- 18808798
TI  - Chapter 10 Dorsomedial nucleus (DMN).

PMID- 18808800
TI  - Chapter 12 Lateral tuberal nucleus.

PMID- 18808799
TI  - Chapter 11 Infundibular nucleus (arcuate nucleus), subventricular nucleus and
      median eminence (Fig. 11A).

PMID- 18808802
TI  - Chapter 14 Lateral hypothalamic area (LHA), including the perifornical area and
      intermediate hypothalamic area (IHA).

PMID- 18808801
TI  - Chapter 13 Tuberomamillary complex.

PMID- 18808803
TI  - Chapter 15 Subthalamic nucleus and Zona Incerta.

PMID- 18808805
TI  - Chapter 17 Vascular supply and vascular disorders.

PMID- 18808804
TI  - Chapter 16 Corpora mamillaria.

PMID- 18808807
TI  - Chapter 19 tumors.

PMID- 18808806
TI  - Chapter 18 Disorders of development and growth.

PMID- 18808808
TI  - Chapter 20 Hypothalamic infections.

PMID- 18808809
TI  - Chapter 21 Neuroimmunological disorders.

PMID- 18808810
TI  - Chapter 22 Drinking disorders.

PMID- 18808811
TI  - Chapter 23 Eating disorders (Fig. 23A).

PMID- 18808812
TI  - Chapter 24 Reproduction, olfaction and sexual behavior (Figs. 24A, B).

PMID- 18808813
TI  - Chapter 25 Hypothalamic lesions following trauma and iatrogenic lesions.

PMID- 18808815
TI  - Chapter 27 Schizophrenia and autism.

PMID- 18808814
TI  - Chapter 26 Hypothalamic involvement in psychiatric disorders.

PMID- 18808817
TI  - Chapter 29 Neurodegenerative disorders.

PMID- 18808816
TI  - Chapter 28 Periodic disorders.

PMID- 18808818
TI  - Chapter 30 Autonomic disorders.

PMID- 18808820
TI  - Chapter 32 Miscellaneous hypothalamic syndromes.

PMID- 18808819
TI  - Chapter 31 Pain and addiction.

PMID- 18808821
TI  - Chapter 33 Brain death and 'dead' neurons (Fig. 33A).

PMID- 18808822
TI  - Index of volumes 79 and 80 - the human hypothalamus. Parts I and II.

PMID- 18808823
TI  - Chapter 1 Pain and hyperalgesia: definitions and theories.

PMID- 18808825
TI  - Chapter 3 Nociceptors: neurogenic inflammation.

PMID- 18808824
TI  - Chapter 2 Pain as a disease.

PMID- 18808826
TI  - Chapter 4 Primary hyperalgesia and nociceptor sensitization.

PMID- 18808827
TI  - Chapter 5 Molecular mechanisms of nociception and pain.

PMID- 18808828
TI  - Chapter 6 Anatomy and neurochemistry of the dorsal horn.

PMID- 18808829
TI  - Chapter 7 Pain and the spinal cord.

PMID- 18808830
TI  - Chapter 8 Ascending nociceptive pathways.

PMID- 18808832
TI  - Chapter 10 Brainstem and thalamic relays.

PMID- 18808833
TI  - Chapter 11 Subcortical processing of nociceptive information: basal ganglia and
      amygdala.

PMID- 18808835
TI  - Chapter 13 Descending inhibitory systems.

PMID- 18808834
TI  - Chapter 12 Cortical mechanisms mediating acute and chronic pain in humans.

PMID- 18808836
TI  - Chapter 14 Descending excitatory systems.

PMID- 18808831
TI  - Chapter 9 The dorsal horn and hyperalgesia.

PMID- 18808837
TI  - Chapter 15 Descending pain modulation as a component of homeostasis.

PMID- 18808838
TI  - Chapter 16 Pathological changes in the nociceptor: alterations in TRPV1 activity
      and expression.

PMID- 18808839
TI  - Chapter 17 Cytokines and pain.

PMID- 18808840
TI  - Chapter 18 Itch and cold allodynia.

PMID- 18808841
TI  - Chapter 19 Pathophysiology of nerve injury.

PMID- 18808842
TI  - Chapter 20 Central sensitization following nerve injury: molecular mechanisms.

PMID- 18808843
TI  - Chapter 21 Pain following spinal cord injury: central mechanisms.

PMID- 18808844
TI  - Chapter 22 Contribution of glia to pain processing in health and disease.

PMID- 18808845
TI  - Chapter 23 Sex, gender and pain.

PMID- 18808846
TI  - Chapter 24 Referred pain from internal organs.

PMID- 18808847
TI  - Chapter 25 The autonomic nervous system and pain.

PMID- 18808848
TI  - Chapter 26 Clinical examination.

PMID- 18808849
TI  - Chapter 27 Quantitative sensory testing.

PMID- 18808850
TI  - Chapter 28 Brainstem reflexes and their relevance to pain.

PMID- 18808851
TI  - Chapter 29 Microneurography in the assessment of neuropathic pain.

PMID- 18808853
TI  - Chapter 31 Neuropathological examination of peripheral nerves in painful
      neuropathies (neuralgias).

PMID- 18808852
TI  - Chapter 30 Evoked potentials in the assessment of pain.

PMID- 18808854
TI  - Chapter 32 Brain imaging of pain.

PMID- 18808855
TI  - Chapter 33 Experimental human models of neuropathic pain.

PMID- 18808856
TI  - Chapter 34 Classification of neuropathic pain syndromes based on symptoms and
      signs.

PMID- 18808857
TI  - Chapter 35 Complex regional pain syndrome.

PMID- 18808858
TI  - Chapter 36 Painful entrapment disorders.

PMID- 18808859
TI  - Chapter 37 Pain after surgical interventions.

PMID- 18808860
TI  - Chapter 38 Trigeminal neuralgia and other facial neuralgias.

PMID- 18808861
TI  - Chapter 39 Atypical facial pain and burning mouth syndrome.

PMID- 18808862
TI  - Chapter 40 Painful diabetic neuropathies.

PMID- 18808864
TI  - Chapter 42 Specific painful neuropathies.

PMID- 18808863
TI  - Chapter 41 Painful small-fiber neuropathies.

PMID- 18808865
TI  - Chapter 43 Acute herpes zoster pain.

PMID- 18808866
TI  - Chapter 44 Postherpetic neuralgia.

PMID- 18808867
TI  - Chapter 45 Postamputation pain.

PMID- 18808868
TI  - Chapter 46 Pain following spinal cord injury.

PMID- 18808869
TI  - Chapter 47 Pain in syringomyelia/bulbia.

PMID- 18808870
TI  - Chapter 48 Central post-stroke pain.

PMID- 18808871
TI  - Chapter 49 Pain in multiple sclerosis.

PMID- 18808872
TI  - Chapter 50 Pain in Parkinson's disease.

PMID- 18808873
TI  - Chapter 51 fibromyalgia.

PMID- 18808874
TI  - Chapter 52 Chronic low back pain.

PMID- 18808875
TI  - Chapter 53 Whiplash injury.

PMID- 18808876
TI  - Chapter 54 Pain in somatization disorders and psychiatric illness.

PMID- 18808877
TI  - Chapter 55 Pain in dementia.

PMID- 18808878
TI  - Chapter 56 The measurement and analysis of pain symptoms.

PMID- 18808879
TI  - Chapter 57 Principles of pharmacological treatment.

PMID- 18808880
TI  - Chapter 58 Cognitive behavioral approaches and neuropathic pain.

PMID- 18808882
TI  - Chapter 60 Spinal cord stimulation for neuropathic pain.

PMID- 18808881
TI  - Chapter 59 Neurosurgical treatment of pain.

PMID- 18808884
TI  - Preface.

PMID- 18808885
TI  - Foreword.

PMID- 18808886
TI  - Chapter 1 Historical aspects of motor neuron diseases.

PMID- 18808888
TI  - Chapter 3 Development of the corticospinal system and spinal motor circuits.

PMID- 18808887
TI  - Chapter 2 Comparative anatomy and physiology of the corticospinal system.
AB  - The corticospinal tract provides the most direct pathway over which the cerebral
      cortex controls movement. In rodents and marsupials this influence is exerted
      largely upon interneurons in the dorsal horn of the spinal gray matter. However,
      ascending the phylogenetic scale through carnivores and primates, the number of
      corticospinal axons grows and corticospinal terminations shift progressively
      toward the interneurons of the intermediate zone and ventral horn, ultimately
      forming increasing numbers of synaptic terminations directly on the motoneurons
      themselves. Based on this phylogenetic trend, humans are believed to have more
      direct corticomotoneuronal synapses than any other species, consistent with
      observations that humans suffer more extensive loss of motility from lesions of
      the corticospinal tract than do other mammals. Beyond this phylogenetic trend,
      studies of the corticospinal system in animals have provided insight into the
      motor abnormalities that result from corticospinal lesions in humans.
      Corticospinal lesions impair many functionally related muscles and movements in
      parallel, both because of the divergent output from single corticomotoneuronal
      cells to multiple motoneuron pools, and because of the convergent input to
      different motoneuron pools from large, overlapping cortical territories.
      Furthermore, the weakness, slowness and inflexible, stereotyped movements that
      remain after corticospinal lesions reflect the loss of input to spinal
      interneurons and motoneurons from corticospinal neurons, the discharge frequency
      of which varies with the force, direction and speed of both gross and fine
      movements. That these deficits resulting from corticospinal lesions are more
      prominent in humans than in animals indicates, moreover, that animals make
      greater use of additional descending pathways to control movement. Animal studies
      have shown that although the bulk of the corticospinal tract arises from the
      primary motor cortex, this projection is not the only route via which the brain
      controls movement. Adjacent areas in the frontal and parietal lobes also
      contribute axons to the corticospinal tract, as well as having corticocortical
      connections with the motor cortex. Furthermore, the motor cortex and premotor
      cortex both project to the red nucleus and to the pontomedullary reticular
      formation, from which the rubrospinal and reticulospinal tracts arise. However,
      given the limitations on experimental studies in humans, comparative animal
      studies of the distributed descending system through which the brain controls
      movement continue to provide deeper understanding and insight into the deficits
      resulting from human corticospinal lesions, whether caused by stroke, tumor,
      multiple sclerosis, trauma or ALS.

PMID- 18808889
TI  - Chapter 4 Molecular mechanisms of motor neuron degeneration in amyotrophic
      lateral sclerosis.

PMID- 18808890
TI  - Chapter 5 Cytopathology of the motor neuron.

PMID- 18808892
TI  - Chapter 7 Spinal muscular atrophies and hereditary motor neuropathies.

PMID- 18808891
TI  - Chapter 6 Animal models of motor neuron death.

PMID- 18808893
TI  - Chapter 8 Spinobulbar muscular atrophy (Kennedy's disease).

PMID- 18808894
TI  - Chapter 9 GM(2) gangliosidoses.
AB  - LOGM(2)G results from the defective activity of the lyosomal enzyme beta
      hexosaminidase A. Continued accumulation of undegraded substrate results in
      pathology in the central nervous system. The disease is progressive and disease
      dynamics may vary throughout life. Clinically, the disease variants present a
      remarkable spectrum of phenotypes ranging from the lethal form to a slowly
      progressive disease type. Genotype/phenotype correlations are imperfect.
      Homozygosity for the L444P genotype is almost always associated with the
      infantile form. The pathological mechanism of the central nervous system damage
      is still not fully understood. Neuronal loss and neurodegeneration have been
      reported, as well as gray matter and white matter involvement, leading to
      multisystem expression. Recently, the possibilities of using stem cells to
      replace damaged neurons or enzyme replacement therapy have been suggested for
      several neurodegenerative diseases. The anterior horn cells can theoretically be
      a target for this procedure. In fact, using stem cells engineered to carry a
      normal HEXA gene is potentially more likely to benefit LOGM(2)G cases than
      patients with other forms of motor neuron disease, since in ALS the degenerative
      process will continue and is likely to affect the transplanted cells whereas in
      LOGM(2)G a real correction of the metabolic abnormality could replace damaged
      motor neurons by normal ones.

PMID- 18808896
TI  - Chapter 11 Monomelic amyotrophy of upper or lower limbs.

PMID- 18808895
TI  - Chapter 10 Viral infections of lower motor neurons.

PMID- 18808897
TI  - Chapter 12 Multifocal and other motor neuropathies.

PMID- 18808898
TI  - Chapter 13 Amyotrophic lateral sclerosis.

PMID- 18808899
TI  - Chapter 14 Familial amyotrophic lateral sclerosis.

PMID- 18808900
TI  - Chapter 15 Juvenile amyotrophic lateral sclerosis.
AB  - Several forms of genetically defined juvenile amy-otrophic lateral sclerosis
      (ALS) have now been charac-terized and discussion of these conditions will form
      the basis for this chapter. ALS2 is an autosomal recessive form of ALS with a
      juvenile onset and very slow progression that mapped to chromosome 2q33. Nine
      different mutations have been identified in the ALS2 gene that result in
      premature stop codons, suggesting a loss of function in the gene product, alsin.
      The alsin protein is thought to function as a guanine-nucleotide exchange factor
      for GTPases and may play a role in vesicle transport or membrane trafficking
      processes. ALS4 is an autosomal dominant form of juvenile onset ALS associated
      with slow progression, severe muscle weakness and pyramidal signs, in the absence
      of bulbar and sensory abnormalities. Mutations in the SETX gene cause ALS4, and
      the SETX gene product senataxin may have DNA and RNA helicase activity and play a
      role in the regulation of RNA and/or DNA in the cell. A third form of juvenile
      onset ALS (ALS5) is associated with slowly progressing lower motor neuron signs
      (weak-ness and atrophy) initially of the hands and feet, with eventual bulbar
      involvement. Progressive upper motor neuron disease becomes more obvious with
      time. ALS5 has been linked to a 6 cM region of chromosome 15q15.1-q21.1, but the
      causative gene mutation for ALS5 has yet to be identified. The high degree of
      clin-ical and genetic heterogeneity in the various forms of juvenile ALS can make
      differential diagnosis difficult, other genetic disorders that must be considered
      include: spinal muscular atrophy, hereditary spastic paraplegia, SBMA, GM2
      gangliosidosis and the hereditary motor neuronopathies/motor forms of Charcot
      Marie-Tooth disease. Acquired disorders that must also be consid-ered include
      heavy metal intoxications (especially lead), multifocal motor neuropathy,
      paraneoplastic syndromes, vitamin deficiencies (B12) and infections (HTLV-II, HIV
      and poliomyelitis).

PMID- 18808901
TI  - Chapter 16 Primary lateral sclerosis.

PMID- 18808902
TI  - Chapter 17 Hereditary spastic paraparesis.

PMID- 18808903
TI  - Chapter 18 Toxic disorders of the upper motor neuron system.
AB  - Lathyrism and konzo are two similar self-limiting cortical motor neuron disorders
      characterized by spastic disability of the lower extremities and, in severe
      cases, with disability in the upper extremities and even (in konzo only)
      pseudobulbar dysfunction. They are caused by prolonged and almost exclusive
      dietary dependence on grass pea (lathyrism) or insufficiently processed bitter
      cassava (konzo), with poor nutritional state a significant risk factor and
      excessive exercise an apparent precipitating factor. Only lathyrism has been
      partially modeled in laboratory primates. Experimental studies suggest these
      toxic neurodegenerative disorders are primary neuronopathies dominated by
      bilateral involvement of upper motor neurons and their axonal projections. Those
      cortical motor neurons with the longest axonal projections seem to be most
      vulnerable, possibly because they have the largest dendritic tree and available
      glutamate receptors that are likely targets of the culpable grass pea neurotoxin
      (BOAA) and the neurotoxic cassava metabolites (SCN, OCN ti]Onset of lathyrism and
      konzo is often abrupt, and some degree of clinical improvement is characteristic
      before the clinical signs stabilize into a pure form of spastic para/
      tetraparesis. Clinical progression may occur with continued intake of the
      offending foodstuff. Prolonged lower-level intake of cassava has been associated
      with distinct neurological syndromes in adults, notably an ataxic
      (myelo)neuropathy for which OCN is a likely etiological factor.

PMID- 18808904
TI  - Chapter 19 Therapies in amyotrophic lateral sclerosis: Options for the near and
      far future.

PMID- 18808905
TI  - Chapter 20 Symptomatic therapy and palliative aspects of clinical care.

PMID- 18808906
TI  - Preface.

PMID- 18808907
TI  - Foreword.

PMID- 18808908
TI  - Anatomy and physiology of the basal ganglia: relevance to Parkinson's disease and
      related disorders.

PMID- 18808909
TI  - Functional neurochemistry of the basal ganglia.

PMID- 18808910
TI  - Neurophysiology of basal ganglia diseases.

PMID- 18808911
TI  - Dopamine receptor pharmacology.

PMID- 18808912
TI  - History of Parkinson's disease.

PMID- 18808913
TI  - Epidemiology of Parkinson's disease.

PMID- 18808914
TI  - Neurochemistry of Parkinson's disease.

PMID- 18808915
TI  - The neuropathology of parkinsonism.

PMID- 18808916
TI  - Genetic aspects of Parkinson's disease.

PMID- 18808917
TI  - Imaging Parkinson's disease.

PMID- 18808919
TI  - Scales to measure parkinsonism.

PMID- 18808918
TI  - Parkinson's disease: animal models.

PMID- 18808920
TI  - Motor symptoms in Parkinson's disease.

PMID- 18808921
TI  - Autonomic dysfunction in Parkinson's disease.

PMID- 18808922
TI  - Sleep in Parkinson syndromes.

PMID- 18808923
TI  - Sensory symptoms in Parkinson's disease.

PMID- 18808925
TI  - Clinical features, pathophysiology and treatment of dementia associated with
      Parkinson's disease.

PMID- 18808924
TI  - Speech disorders in Parkinson's disease and the effects of pharmacological,
      surgical and speech treatment with emphasis on Lee Silverman voice treatment
      (LSVT(R)).

PMID- 18808926
TI  - Disorders of mood and affect in Parkinson's disease.

PMID- 18808927
TI  - Neurobehavioral disorders in Parkinson's disease.

PMID- 18808928
TI  - Early detection of Parkinson's disease.

PMID- 18808929
TI  - Mitochondria in the etiology of Parkinson's disease.

PMID- 18808930
TI  - Iron as a trigger of neurodegeneration in Parkinson's disease.

PMID- 18808931
TI  - Oxidative stress and Parkinson's disease.

PMID- 18808932
TI  - Neurotrophic factors and Parkinson's disease.

PMID- 18808933
TI  - Neuroinflammation and Parkinson's disease.

PMID- 18808934
TI  - Excitotoxicity.

PMID- 18808935
TI  - Protein-handling dysfunction in Parkinson's disease.

PMID- 18808936
TI  - Programmed cell death in Parkinson's disease.

PMID- 18808937
TI  - Preface.

PMID- 18808938
TI  - Foreword.

PMID- 18808939
TI  - Physical therapy in Parkinson's disease.

PMID- 18808940
TI  - Neuroprotection in Parkinson's disease: clinical trials.

PMID- 18808941
TI  - Levodopa.

PMID- 18808942
TI  - Dopamine agonists.

PMID- 18808944
TI  - Anticholinergic medications.

PMID- 18808943
TI  - Monoamine oxidase A and B inhibitors in Parkinson's disease.

PMID- 18808945
TI  - Antiglutamatergic drugs in the treatment of Parkinson's disease.

PMID- 18808946
TI  - Investigational drugs.

PMID- 18808948
TI  - Motor and non-motor fluctuations.

PMID- 18808947
TI  - The importance of patient groups and collaboration.

PMID- 18808949
TI  - Levodopa-induced dyskinesias in Parkinson's disease.

PMID- 18808950
TI  - Treatment-induced mental changes in Parkinson's disease.

PMID- 18808951
TI  - Ablative surgery for the treatment of Parkinson's disease.

PMID- 18808952
TI  - Deep brain stimulation.

PMID- 18808953
TI  - Transplantation.

PMID- 18808954
TI  - Gene therapy approaches for the treatment of Parkinson's disease.

PMID- 18808955
TI  - Multiple system atrophy.

PMID- 18808956
TI  - Progressive supranuclear palsy.

PMID- 18808958
TI  - Infectious basis to the pathogenesis of Parkinson's disease.

PMID- 18808957
TI  - Corticobasal degeneration.

PMID- 18808959
TI  - Toxic causes of parkinsonism.

PMID- 18808960
TI  - Drug-induced parkinsonism.

PMID- 18808961
TI  - Vascular parkinsonism.

PMID- 18808962
TI  - Old age and Parkinson's disease.

PMID- 18808963
TI  - Other degenerative processes.

PMID- 18808964
TI  - Hydrocephalus and structural lesions.

PMID- 18808965
TI  - Calcification of the Basal Ganglia.

PMID- 18808966
TI  - Trauma and Parkinson's disease.

PMID- 18808967
TI  - Psychogenic parkinsonism.

PMID- 18808968
TI  - Parkinsonism and dystonia.

PMID- 18808969
TI  - Dementia with Lewy bodies.

PMID- 18808971
TI  - Foreword.

PMID- 18808970
TI  - Myoclonus and parkinsonism.

PMID- 18808972
TI  - Introduction to HIV infection and neuro-AIDS.

PMID- 18808973
TI  - Neuroepidemiology of HIV/AIDS.

PMID- 18808975
TI  - The neuropathogenesis of HIV-1 infection.

PMID- 18808974
TI  - HIV neurology in the developing world.

PMID- 18808976
TI  - Neurological sequelae of primary HIV infection.

PMID- 18808977
TI  - AIDS dementia complex.

PMID- 18808978
TI  - Neurocognitive assessment of persons with HIV disease.

PMID- 18808979
TI  - HIV myelopathy.

PMID- 18808980
TI  - Peripheral neuropathy in HIV infection.

PMID- 18808982
TI  - Cerebral toxoplasmosis in AIDS.

PMID- 18808981
TI  - Myopathy in HIV infection.

PMID- 18808983
TI  - Cryptococcal infection.

PMID- 18808984
TI  - Progressive multifocal leukoencephalopathy.

PMID- 18808985
TI  - Other opportunistic infections of the central nervous system in AIDS.

PMID- 18808986
TI  - Primary central nervous system lymphoma.

PMID- 18808987
TI  - Neuroimaging of the HIV/AIDS patient.

PMID- 18808988
TI  - Cerebrospinal fluid markers in central nervous system HIV infection and AIDS
      dementia complex.

PMID- 18808989
TI  - The neuropathology of HIV.

PMID- 18808991
TI  - Preface.

PMID- 18808990
TI  - Neuropharmacology of HIV/AIDS.

PMID- 18808992
TI  - Foreword.

PMID- 18808993
TI  - Congenital myopathies.

PMID- 18808994
TI  - Myopathies with early contractures.

PMID- 18808996
TI  - Periodic paralysis.

PMID- 18808995
TI  - Myotonic disorders.

PMID- 18808997
TI  - Malignant hyperthermia and associated conditions.

PMID- 18808998
TI  - Mitochondrial encephalomyopathies.

PMID- 18809000
TI  - Disorders of lipid metabolism.

PMID- 18808999
TI  - Disorders of carbohydrate metabolism.

PMID- 18809001
TI  - Investigation of metabolic myopathies.

PMID- 18809002
TI  - Lysosomal myopathies.

PMID- 18809003
TI  - Distal myopathies.

PMID- 18809004
TI  - Hereditary inclusion body myopathy and other rimmed vacuolar myopathies.

PMID- 18809005
TI  - Inclusion body myositis.

PMID- 18809006
TI  - Autoimmune inflammatory myopathies.

PMID- 18809007
TI  - Infective myopathies.

PMID- 18809008
TI  - Toxic and iatrogenic myopathies.

PMID- 18809009
TI  - Endocrine myopathies.

PMID- 18809010
TI  - Muscle diseases and aging.

PMID- 18809011
TI  - Muscle cramp syndromes.

PMID- 18809012
TI  - Miscellaneous myopathies.

PMID- 18809013
TI  - Preface: Embryology is the essence of understanding development.

PMID- 18809015
TI  - Axes and gradients of the neural tube for a morphological/molecular genetic
      classification of nervous system malformations.

PMID- 18809016
TI  - Holoprosencephaly.

PMID- 18809017
TI  - Septo-optic-pituitary dysplasia.

PMID- 18809018
TI  - Rhombencephalosynapsis.

PMID- 18809019
TI  - Embryology and malformations of the forebrain commissures.

PMID- 18809020
TI  - Disorders of segmentation of the neural tube: Chiari malformations.

PMID- 18809021
TI  - Disorders of segmentation of the neural tube: agenesis of selective neuromeres.

PMID- 18809022
TI  - Cerebellar hypoplasias.

PMID- 18809023
TI  - Tuberous sclerosis.

PMID- 18809024
TI  - Hemimegalencephaly syndrome.

PMID- 18809025
TI  - Periventricular nodular heterotopia.

PMID- 18809026
TI  - Subcortical laminar (band) heterotopia.

PMID- 18809027
TI  - Lissencephaly type I.

PMID- 18809028
TI  - Lissencephaly type II.

PMID- 18809029
TI  - Schizencephaly.

PMID- 18809030
TI  - Neural tube programming and the pathogenesis of craniofacial clefts, part I: the
      neuromeric organization of the head and neck.

PMID- 18809031
TI  - Neural tube programming and the pathogenesis of craniofacial clefts, part II:
      mesenchyme, pharyngeal arches, developmental fields; and the assembly of the
      human face.

PMID- 18809032
TI  - The oral-facial-digital syndromes.

PMID- 18809033
TI  - Congenital vascular malformations in childhood.

PMID- 18809034
TI  - Acquired, induced and secondary malformations of the developing central nervous
      system.

PMID- 18809035
TI  - Epilepsy in patients with cerebral malformations.

PMID- 18809036
TI  - Neuromuscular disorders associated with cerebral malformations.

PMID- 18809037
TI  - Neuroendocrine complications of central nervous system malformations.

PMID- 18809038
TI  - Cerebral dysgeneses associated with chromosomal disorders.

PMID- 18809039
TI  - Cerebral dysgeneses secondary to metabolic disorders in fetal life.

PMID- 18809040
TI  - Imaging malformations of cortical development.

PMID- 18809041
TI  - Clinical neurophysiology of cortical malformations: magnetoencephalography and
      electroencephalography.

PMID- 18809042
TI  - Molecular genetic testing and genetic counseling.

PMID- 18809043
TI  - Embryology and neuropathological examination of central nervous system
      malformations.

PMID- 18809044
TI  - Medical treatment in children with central nervous system malformations.

PMID- 18809045
TI  - Surgical treatment of central nervous system malformations.

PMID- 18809046
TI  - Neurorehabilitation of children with cerebral palsy.

PMID- 18809047
TI  - Educational, cognitive, behavioral and language development issues.

PMID- 18809048
TI  - Internal supravesical hernia.
AB  - Internal supravesical hernia is a rare cause of intestinal obstruction and a
      clinical diagnostic problem. We demonstrate its computed tomography (CT)
      appearance and believe familiarity with the anatomy of the supravesical fossa may
      allow the preoperative diagnosis.

PMID- 18809049
TI  - A prospective, randomized, controlled, multicenter study of a real-time,
      intraoperative probe for positive margin detection in breast-conserving surgery.
AB  - BACKGROUND: This randomized, double-arm trial was designed to study the benefit
      of a novel device (MarginProbe, Dune Medical Devices, Caesarea, Israel) in
      intraoperative margin assessment for breast-conserving surgery (BCS) and the
      associated reduction in reoperations. METHODS: In the device group, the probe was
      applied to the lumpectomy specimen and additional tissue was excised according to
      device readings. Study arms were compared by reoperation rates and by correct
      surgical reaction confirmed by histology. RESULTS: Three hundred patients were
      enrolled. Device use was associated with improved correct surgical reaction,
      defined as additional re-excision in all histologically detected positive
      margins, with tumor within 1 mm of inked margin. The repeat lumpectomy rate was
      significantly reduced by 56% in the device arm: 5.6% versus 12.7% in the control
      arm. There were no differences in excised tissue volume or cosmetic outcome.
      CONCLUSIONS: Intraoperative use of the MarginProbe for positive margin detection
      is safe and effective in BCS and decreases the rate of repeat operations.

PMID- 18809050
TI  - The survival impact of the choice of surgical procedure after ipsilateral breast
      cancer recurrence.
AB  - BACKGROUND: Many women with breast cancer recurrence previously treated with
      breast-conservation therapy desire repeat lumpectomies. We hypothesized that
      women undergoing mastectomy for breast cancer recurrence would show superior
      survival. METHODS: Patients who previously received breast-conservation therapy
      diagnosed with an ipsilateral breast cancer recurrence between 1988 and 2004 were
      identified using the Surveillance, Epidemiology, and End Results database.
      Univariate survival analysis was performed using the Kaplan-Meier method. Cox
      regression was used for multivariate analysis. RESULTS: Criteria for analysis
      were met in 747 patients. Of those, 24% underwent lumpectomy. On univariate
      analysis, patients undergoing lumpectomy had worse overall survival (P = .03).
      Five-year survival was 67% versus 78% for the lumpectomy and mastectomy groups,
      respectively. On multivariate analysis, mastectomy remained significantly
      associated with better survival with a hazard ratio of .5 (P = .003).
      CONCLUSIONS: The use of lumpectomy for ipsilateral breast cancer recurrence
      previously treated with breast-conservation therapy should generally be
      discouraged.

PMID- 18809051
TI  - Noncompliance with adjuvant radiation, chemotherapy, or hormonal therapy in
      breast cancer patients.
AB  - INTRODUCTION: There is little information on patient-driven noncompliance of
      adjuvant therapies and its consequences. METHODS: This retrospective study
      compares clinical, pathological features and outcomes of breast cancer patients
      who were compliant to recommended radiation, chemotherapy, and hormonal therapies
      to those who were noncompliant. RESULTS: Noncompliance rates for chemotherapy,
      radiation, and tamoxifen were 31 of 421 (7%), 30 of 855 (4%), and 294 of (37%)
      respectively. Old age was associated with noncompliance to chemotherapy and
      radiation, but younger women tend to be more often noncompliant to tamoxifen.
      Noncompliance with chemotherapy or radiation did not significantly affect 5-year
      local and distant disease-free survival rates. Noncompliance with tamoxifen was
      associated with decreased 5-year local and distant disease-free survivals (87%
      versus 96%, 76% versus 87%, respectively, P < .001). CONCLUSION: Noncompliance
      with tamoxifen is the most common, resulting in significantly increased risk of
      local and distant disease recurrence.

PMID- 18809052
TI  - Improved breast cancer survival among hormone replacement therapy users is
      durable after 5 years of additional follow-up.
AB  - BACKGROUND: We previously reported that breast cancer patients who used hormone
      replacement therapy (HRT) had significantly lower stage tumors and higher
      survival than never-users. We present an update with longer follow-up, HRT use
      data, and in vitro research. METHODS: Our database of 292 postmenopausal breast
      cancer patients was updated to include HRT type, duration, and disease status. In
      vitro effects of estrogen (E) and/or medroxyprogesterone (MPA) on breast cancer
      cell growth were measured. RESULTS: Tumor prognostic factors were better and
      survival rates higher for both E and combination HRT users of any duration. Use
      greater than 10 years correlated with node-negative disease, mammographically
      detected tumors, and 100% survival. E supported minimal proliferation; MPA
      induced cell death; E+MPA results were similar to E alone. CONCLUSIONS: HRT
      users, regardless of type or duration of HRT use, continued to have higher
      survival rates. In vitro results supported the clinical finding that outcomes for
      users of E and E+MPA were similar.

PMID- 18809053
TI  - Immediate latissimus dorsi miniflap volume replacement for partial mastectomy:
      use of intra-operative frozen sections to confirm negative margins.
AB  - BACKGROUND: Latissimus dorsi (LD) miniflap volume replacement is used for
      immediate reconstruction after partial mastectomy. This prospectively collected
      series was analyzed to evaluate the accuracy of intraoperative frozen sections.
      METHODS: After partial mastectomy, "bed biopsies" were submitted for
      intraoperative frozen-section analysis. If disease free, volume replacement was
      undertaken; if involved, targeted re-excisions were taken. Demographic,
      pathological, and outcome data were recorded. The proportion of breast excised
      was calculated. Local recurrences were recorded. RESULTS: One hundred ten partial
      mastectomies with LD miniflap volume replacement were completed. The median
      proportion of breast excised was 28% (maximum 72%); median weight 207 g. Frozen
      sections were positive in 33% of patients with a sensitivity of 83% and accuracy
      of 96% when compared with paraffin sections. Local recurrence occurred in one
      case. The median follow-up was 41.4 months. CONCLUSIONS: LD miniflap volume
      replacement extends the role of breast-conserving surgery. Frozen-section
      analysis of bed biopsies facilitates a single-stage procedure.

PMID- 18809054
TI  - Impact of neoadjuvant chemotherapy on rate of tissue expander/implant loss and
      progression to successful breast reconstruction following mastectomy.
AB  - PURPOSE: We examined the frequency and causes of tissue expander (TE) and
      permanent implant (PI) reconstruction failure in patients undergoing neoadjuvant
      chemotherapy. METHODS AND MATERIALS: Charts were reviewed from 120 patients with
      clinical stage II/III breast cancer enrolled between 2004 and 2007 into a
      prospective clinical trial of neoadjuvant chemotherapy. Patient demographics,
      tobacco use, radiation treatment, and data relating to the loss of TE, as well as
      progression to PI and PI loss, were collected. RESULTS: Of 120 patients, 61
      underwent 75 mastectomies. Twenty-six patients had 34 TEs placed at the time of
      mastectomy. Eleven (32%) TEs required removal prior to definitive reconstruction.
      Fourteen (41%) TEs successfully progressed to PI exchange. Four of the PIs
      required removal. TE loss occurred most frequently due to infection and
      extrusion. Radiation, smoking history, or elevated body mass index (BMI) did not
      significantly affect reconstruction loss. CONCLUSION: Thirty-eight percent of
      immediate TEs or PI placements at the time of mastectomy failed to progress to
      definitive reconstruction in patients receiving neoadjuvant therapy, suggesting
      that reconstruction with TEs or PI reconstruction should be used cautiously in
      this patient population.

PMID- 18809055
TI  - Effectiveness of a noninvasive digital infrared thermal imaging system in the
      detection of breast cancer.
AB  - BACKGROUND: Digital infrared thermal imaging (DITI) has resurfaced in this era of
      modernized computer technology. Its role in the detection of breast cancer is
      evaluated. METHODS: In this prospective clinical trial, 92 patients for whom a
      breast biopsy was recommended based on prior mammogram or ultrasound underwent
      DITI. Three scores were generated: an overall risk score in the screening mode, a
      clinical score based on patient information, and a third assessment by artificial
      neural network. RESULTS: Sixty of 94 biopsies were malignant and 34 were benign.
      DITI identified 58 of 60 malignancies, with 97% sensitivity, 44% specificity, and
      82% negative predictive value depending on the mode used. Compared to an overall
      risk score of 0, a score of 3 or greater was significantly more likely to be
      associated with malignancy (30% vs 90%, P < .03). CONCLUSION: DITI is a valuable
      adjunct to mammography and ultrasound, especially in women with dense breast
      parenchyma.

PMID- 18809056
TI  - Does oncotype DX recurrence score affect the management of patients with early
      stage breast cancer?
AB  - BACKGROUND: Oncotype DX is a 21-gene assay that calculates a risk of distant
      recurrence in women with estrogen-receptor-positive, lymph node-negative breast
      cancer. The purpose of this study was to determine whether the results of
      Oncotype DX influence the decision to administer chemotherapy. METHODS: A
      retrospective study was performed on 85 consecutive patients with estrogen
      receptor-positive, lymph node-negative breast cancer who had an Oncotype DX
      recurrence score (RS) obtained. Tumor size, tumor grade, and treatment were then
      compared within each risk category. Statistical analysis was performed using
      STATA software. RESULTS: Tumors that were high grade and Her-2/neu positive more
      frequently had a high RS. Treatment was changed as a result of Oncotype DX in 44%
      of patients. CONCLUSIONS: Oncotype DX RS is significantly related to tumor grade
      and Her2/neu status. In this study, the treatment of 44% of patients was altered
      as a consequence of Oncotype DX RS.

PMID- 18809057
TI  - Optimal treatment of multiple ipsilateral primary breast cancers.
AB  - INTRODUCTION: The success of breast-conservation therapy (BCT) for patients with
      multiple ipsilateral invasive breast cancers (MIBC) is sparsely documented.
      METHODS: A retrospective review of single-institution experience. Patients with 2
      or more invasive cancers separated by normal breast tissue were included;
      patients with 1 invasive cancer with additional in situ lesions and those
      receiving neoadjuvant therapy were excluded. RESULTS: One hundred forty-nine
      patients were treated over 19 years. Fifty-eight (39%) patients underwent BCT.
      Preoperatively, multiple tumors were suspected in more mastectomy patients than
      BCT patients (75% versus 62%). Most patients had 2 tumors and 1 histology. Fifty
      five percent of patients with tumors within 1 quadrant underwent BCT versus 10%
      of patients with tumors in more than 1 quadrant. One hundred eight patients
      underwent sentinel lymph node (SLN) biopsy. Twenty-seven percent (34) were SLN
      positive. There were no regional recurrences among the SLN-negative patients. Six
      patients recurred: 1 nodal, 1 local, and 4 distant. The locoregional BCT
      recurrence rate was 3.4%. DISCUSSION: MIBC patients can safely undergo BCT with
      low recurrence risk. SLNB can be performed with minimal risk of regional
      recurrence.

PMID- 18809058
TI  - Vascular calcifications on screening mammography identify women with increased
      risk of coronary artery disease and diabetes.
AB  - BACKGROUND: Mammographic breast arterial calcifications (BAC) have been reported
      in women with diabetes and coronary artery disease (CAD). This prospective study
      further investigates the clinical significance of BAC, CAD, and diabetes.
      METHODS: Women undergoing screening mammography were prospectively evaluated for
      mammographic BAC. The association among BAC, CAD, and diabetes was statistically
      evaluated. RESULTS: Of 1,000 consecutive women undergoing screening mammography,
      181 had a history of CAD and/or diabetes. Of those women without diabetes or
      heart disease, 86 of 819 (10.5%) had BAC. One hundred forty women had diabetes,
      of whom 57 (40.7%) had BAC, and 72 women had CAD, of whom 36 (50%) had BAC. The
      association among BAC, CAD, and diabetes was highly significant (P <.0001, 95%
      confidence interval [CI]). The odds ratio of having diabetes or CAD with BAC is
      4.3 and 3.6 times greater than the odds of having these diseases without BAC.
      COMMENTS: This large prospective study indicated a significant association
      between BAC identified on screening mammography and a personal history of CAD and
      diabetes, indicating that screening mammography may identify women at increased
      risk for these diseases.

PMID- 18809059
TI  - Sclerotherapy for the treatment of postmastectomy seroma.
AB  - BACKGROUND: Seroma is a common complication after mastectomy. We review our
      experience with sclerotherapy for postmastectomy seroma management. METHODS:
      Patients who underwent outpatient sclerotherapy for postmastectomy seroma were
      reviewed. Ninety-five percent ethyl alcohol or povidone iodine, which was
      administered by way of percutaneous catheter, was the initial sclerosant, and
      dwell time was 20 to 30 minutes. Povidone iodine solution was instilled 2 to 3
      times daily. Catheters were removed when output reached <30 mL/d or when cavity
      size was <20 ml by sinogram. RESULTS: Sixteen patients (18 seromas) had
      sclerotherapy initiated at median of 34 days after surgery. Mean number of
      treatment days was 3 (median duration 16). Seven patients (44%) developed
      infection during treatment, which was associated with increased duration. Three
      seromas recurred and were successfully treated with single aspiration. COMMENTS:
      Sclerotherapy is a feasible treatment for chronic seroma after mastectomy. Longer
      treatment duration was associated with infection; antibiotic prophylaxis should
      be considered. Research is necessary to determine optimal regimens and
      superiority over other approaches.

PMID- 18809060
TI  - Patient satisfaction and quality of life after MammoSite breast brachytherapy.
AB  - PURPOSE: To perform a satisfaction/quality-of-life (QOL) survey of patients
      undergoing MammoSite brachytherapy (MBT; Hologic, Inc, Marlborough, MA). METHODS:
      We asked patients 15 questions regarding treatment decision-making, and
      experience on-therapy/post-treatment. RESULTS: A total of 52 patients responded
      (median follow-up 30 months). Regarding decision-making, 5.8% viewed the
      avoidance of mastectomy as "not important." If MBT were not available, 55.8%
      would opt for whole-breast radiotherapy (WBRT) without difficulty, 28.8% would
      have significant travel/financial difficulty, and 15.4% would refuse
      radiotherapy/opt for mastectomy. Regarding choice factors, patients selected
      "focused therapy" (44.2%), "convenience" (36.5%), and "cutting edge" (17.3%). A
      total of 61.5% patients were not concerned about a second surgical procedure;
      90.4% were not/somewhat concerned about infection. During treatment, 73.1%
      reported no pain/discomfort with catheter, 73.1% no wound difficulty, 51.0% no
      pain during removal, and 71.2% no pain post-treatment. A total of 98.1% of
      patients rated the experience good/excellent, 90.4% reported no/minor side
      effects, 92.3% rated cosmesis good/excellent, 98.1% were very/extremely likely to
      choose MBT again, and 100% would recommend MBT. CONCLUSIONS: QOL is high
      during/after MBT. More data are needed from ongoing trials to compare with WBRT.

PMID- 18809061
TI  - Mucinous breast carcinoma: a large contemporary series.
AB  - BACKGROUND: Mucinous breast cancer is typically associated with a favorable
      prognosis. This study aimed to assess recent trends and prognostic features in
      the treatment of mucinous breast carcinoma. METHODS: A retrospective review of
      our database of patients who presented with mucinous breast cancer was performed.
      We evaluated patient and tumor characteristics and examined the relationships
      between these factors and risk for locoregional recurrence. RESULTS: One hundred
      eleven patients with mucinous breast cancer were identified. Seventy-one (64%)
      underwent lumpectomy with radiotherapy. Fourteen (13%) had lymph node metastasis,
      and node positivity was associated with larger tumor size; node-positive patients
      had a mean tumor size of 2.7 cm compared with 1.5 cm for node-negative patients
      (P = .0003). No patients with tumor size <1 cm had lymph node metastasis. Five
      patients (5%) had local and/or distant recurrence. CONCLUSIONS: Mucinous breast
      cancer is associated with a low recurrence rate as well as a low incidence of
      lymph node metastasis. In patients with small (<1 cm) tumors, consideration for
      deferring nodal evaluation may be made.

PMID- 18809062
TI  - Invasive local recurrence increased after radiation therapy for ductal carcinoma
      in situ.
AB  - BACKGROUND: It is thought that equal numbers of invasive and noninvasive
      recurrences develop after conservative treatment for ductal carcinoma in situ. We
      analyzed our data to see if this was true. METHODS: A prospective database of 878
      conservatively treated patients with ductal carcinoma in situ was analyzed.
      RESULTS: Among 551 excision patients, there were 88 recurrences. Thirty-five
      percent were invasive. Among 327 excision plus radiotherapy patients, there were
      59 recurrences. Fifty-three percent were invasive. In an attempt to predict which
      patients develop invasive recurrences, prolonged time to recurrence was the only
      statistically significant factor. CONCLUSIONS: The median time to local
      recurrence for irradiated patients was more than twice as long when compared with
      nonirradiated patients, during which there is more time for local recurrence to
      progress to invasion. Irradiated patients had more breast scarring, making
      diagnosis by palpation and mammography harder. Irradiated patients develop
      invasive recurrences at a statistically higher rate than nonirradiated patients.
      Follow-up evaluation with magnetic resonance imaging should be considered.

PMID- 18809063
TI  - Do additional shaved margins at the time of lumpectomy eliminate the need for re
      excision?
AB  - BACKGROUND: Most women diagnosed with breast cancer undergo breast-conservation
      surgery. Re-excision rates for positive margins have been reported to be greater
      than 50%. The purpose of our study was to determine if removing additional shaved
      margins from the lumpectomy cavity at the time of lumpectomy reduces re
      excisions. METHODS: A retrospective study was performed on 125 women who had
      undergone lumpectomy with additional shaved margins taken from the lumpectomy
      cavity. Pathology reports were reviewed for tumor size and histology, lumpectomy
      and additional margin status, and specimen and margin volume. RESULTS: If
      additional margins were not taken, 66% would have required re-excision. Because
      of taking additional shaved margins, re-excision was eliminated in 48%.
      CONCLUSION: Excising additional shaved margins at the original surgery reduced
      reoperations by 48%. There is a balance between removing additional margins and
      desirable cosmesis after breast-conservation surgery. The decision to take extra
      margins should be based on the surgeon's judgment.

PMID- 18809064
TI  - Improvement in sentinel node biopsy results in a teaching community hospital:
      results of a multidisciplinary quality improvement program.
AB  - BACKGROUND: In 2001 we reported poor results for sentinel node biopsy and marked
      variability among surgeons. Subsequently, we initiated a multidisciplinary
      protocol involving standardized radiocolloid injection, physician education, and
      surgeon proctoring. METHODS: The current study presents follow-up data (2004
      2006) after this quality improvement initiative. Data recorded included technical
      details and patient factors, related to each surgeon. Results were compared with
      our previously published data. RESULTS: The overall identification rate was
      improved markedly from 2001 (92% vs 66%). Eleven general surgeons performed 151
      sentinel node biopsies. Seven surgeons had a 100% identification rate, the others
      had identification rates of 84% (N = 44), 86% (N = 29), 92% (N = 12), and 0% (N =
      1). Differences still persist among surgeons, including number of sentinel nodes
      sampled, performance of axillary dissections, and breast conservation.
      CONCLUSIONS: A multidisciplinary protocol improved sentinel node biopsy
      performance in a community teaching hospital. However, further work is needed to
      standardize and improve overall breast surgery results.

PMID- 18809065
TI  - Regional variation in breast cancer treatment throughout the United States.
AB  - BACKGROUND: It has been proposed that initial treatment for breast cancer varies
      greatly across the United States. However, one question that has not been
      answered completely is whether or not geographic location itself is an
      independent variable with regard to treatment. METHODS: The American College of
      Surgeons National Cancer Database Benchmark Reports (NCDB) were used to examine
      initial breast cancer treatment performed throughout the United States during the
      study period 1999-2003. These data were then stratified with regard to geographic
      region in accordance with the US Census Bureau classifications. RESULTS: There
      was a statistically significant relationship between geographic region and
      initial treatment of breast cancer. Although there were statistically significant
      relationships between race and geographic region and stage and geographic region,
      when the data were controlled for stage and race, the regional differences
      persisted. Stage-for-stage and within each racial cohort, the geographic
      differences in treatment were still statistically significant. DISCUSSION: This
      review suggests that geographic location within the United States is an
      independent variable with regard to breast cancer treatment.

PMID- 18809066
TI  - Nipple-sparing mastectomy--initial experience at a tertiary center.
AB  - BACKGROUND: Nipple-sparing mastectomy (NSM) combines skin-sparing mastectomy with
      preservation of the nipple-areolar dermis and intraoperative pathologic
      assessment of the nipple core. We evaluated our initial experience with NSM in
      terms of clinical outcomes. METHODS: An Institutional Review Board-approved
      retrospective review of patients undergoing NSM between November 2005 and June
      2007 was performed. RESULTS: Eighteen NSM and two areola-sparing mastectomies
      were performed. Indications for surgery were invasive cancer (n = 4), ductal
      carcinoma in situ (DCIS) (n = 5), pseudoangiomatous stromal hyperplasia (n = 3),
      and risk reduction (n = 8). The average distance of tumor from the nipple on
      imaging was 4.8 cm (range 4 to 5.7). Nipple cores were all benign, and 2 patients
      developed self-limited superficial desquamation of the nipple. At a mean follow
      up of 10.8 months, all nipple-areolar complexes were intact, and there were no
      local or systemic recurrences. CONCLUSIONS: NSM can be successfully achieved with
      low morbidity in appropriately selected patients.

PMID- 18809067
TI  - Transaxillary retromammary route approach of video-assisted breast surgery
      enables the inner-side breast cancer to be resected for breast conserving
      surgery.
AB  - BACKGROUND: Endoscopic surgery for inner-side breast cancer usually is performed
      by periareolar approach, but leaves deformation or malposition, and sensory
      disturbance. We devised an approach of retromammary route without subcutaneous
      removal, from an axillary skin incision, to treat distant cancers and also to
      preserve sensation to skin touch. METHODS: We have performed video-assisted
      breast surgery on 230 patients. The transaxillary retromammary-route approach was
      performed on 20 patients with early breast cancer. From a 2.5-cm axillary
      incision, we dissected the major pectoral muscle fascia to detach retromammary
      tissue. We cut the proximal side of the gland vertically, and dissected the skin
      flap over the tumor by the tunnel method. Then we cut each side of the gland
      vertically and removed it through the axillary port. RESULTS: All surgical
      margins were negative. The surgical time was 45 minutes longer than the
      conventional video-assisted breast surgery. The postoperative esthetic results
      were good. CONCLUSIONS: The transaxillary retromammary-route approach leaves no
      injury on whole breast, and can become a single standard method for breast
      conserving surgery wherever a cancer is situated.

PMID- 18809068
TI  - Peritoneal cytology in colorectal cancer: incidence and prognostic value.

PMID- 18809069
TI  - Caution when reconsidering empiric antimicrobial therapy for methicillin
      resistant Staphylococcus aureus skin and soft-tissue infections.

PMID- 18809070
TI  - Re: does Barrett's esophagus impact outcome after laparoscopic Nissen
      fundoplication?

PMID- 18809071
TI  - Analytical applications of second-order calibration methods.
AB  - Second-order calibration methods are gaining widespread acceptance among the
      analytical community mainly because: (1) a wide range of analytical
      instrumentation is available that enables high dimensionality data to be
      obtained; (2) the chemometric techniques for treating these data are highly
      developed; and (3) they have the so-called "second-order advantage", i.e. they
      can predict the concentration of the analyte of interest even in the presence of
      unknown interferents. This also enables several analytes to be determined
      simultaneously. In this paper we describe the most common instrumental and
      chemometric techniques used in second-order calibration and discuss their
      applications since 2000. First, we introduce briefly the techniques and then we
      comment the applications. Given the practical nature of this paper, we have
      classified the techniques according to five fields of application:
      pharmaceuticals, biological matrices, foods, environmental matrices and synthetic
      matrices.

PMID- 18809072
TI  - A critical review in calibration methods for solid-phase microextraction.
AB  - Solid-phase microextraction (SPME) was developed to address the need for rapid
      sampling and sample preparation, both in the laboratory and on-site. Unlike
      traditional sample preparation methods, SPME is a non-exhaustive extraction
      technique in which only a small portion of the target analyte is removed from the
      sample matrix. Therefore, calibration of SPME for quantitative analysis is very
      important. In this review, we summarized the proposed SPME calibration methods
      and the characteristics of these methods were discussed.

PMID- 18809073
TI  - Evaluation of alternate lines of Fe for sequential multi-element determination of
      Cu, Fe, Mn and Zn in soil extracts by high-resolution continuum source flame
      atomic absorption spectrometry.
AB  - The usefulness of the secondary line at 252.744nm and the approach of side pixel
      registration were evaluated for the development of a method for sequential multi
      element determination of Cu, Fe, Mn and Zn in soil extracts by high-resolution
      continuum source flame atomic absorption spectrometry (HR-CS FAAS). The influence
      of side pixel registration on the sensitivity and linearity was investigated by
      measuring at wings (248.325, 248.323, 248.321, 248.329, and 248.332nm) of the
      main line for Fe at 248.327nm. For the secondary line at 252.744nm or side pixel
      registration at 248.325nm, main lines for Cu (324.754nm), Mn (279.482nm) and Zn
      (213.875nm), sample flow-rate of 5.0mLmin(-1) and calibration by matrix matching,
      analytical curves in the 0.2-1.0mgL(-1) Cu, 1.0-20.0mgL(-1) Fe, 0.2-2.0mgL(-1)
      Mn, 0.1-1.0mgL(-1) Zn ranges were obtained with linear correlations better than
      0.998. The proposed method was applied to seven soil samples and two soil
      reference materials (IAC 277; IAC 280). Results were in agreement at a 95%
      confidence level (paired t-test) with reference values. Recoveries of analytes
      added to soil extracts containing 0.15 and 0.30mgL(-1) Cu, 7.0 and 14mgL(-1) Fe,
      0.60 and 1.20mgL(-1) Mn, 0.07 and 0.15mgL(-1) Zn, varied within the 94-99, 92-98,
      93-101, and 93-103% intervals, respectively. The relative standard deviations
      (n=12) were 2.7% (Cu), 1.4% (Fe - 252.744nm), 5.7% (Fe - 248.325nm), 3.2% (Mn)
      and 2.8% (Zn) for an extract containing 0.35mgL(-1) Cu, 14mgL(-1) Fe, 1.1mgL(-1)
      Mn and 0.12mgL(-1) Zn. Detection limits were 5.4microgL(-1) Cu, 55microgL(-1) Fe
      (252.744nm), 147microgL(-1) Fe (248.325nm), 3.0microgL(-1) Mn and 4.2microgL(-1)
      Zn.

PMID- 18809074
TI  - Recognition of phospho sugars and nucleotides with an array of boronic acid
      appended bipyridinium salts.
AB  - The solution-phase sensor array of three cationic bis-boronic acid appended
      benzyl viologens (BBV) and the anionic fluorescent dye, 8-hydroxypyrene-1,3,6
      trisulfonic acid trisodium salt (HPTS), is able to discriminate among five
      phospho sugars, four nucleotides and three neutral saccharides in aqueous
      buffered solution at low mM concentrations. Linear discriminant analysis,
      principal component analysis, and hierachical cluster analysis studies showed the
      "discrimination limit" (lowest analyte concentration where the discrimination is
      still 100%) to be 4mM. Calculated K(b) and F(max)/F(0) values from binding curves
      of the three BBVs with 1-12 were also used to perform multi-variate analyses with
      very good discrimination results.

PMID- 18809075
TI  - Optimization of headspace solid-phase microextraction for analysis of ethyl
      carbamate in alcoholic beverages using a face-centered cube central composite
      design.
AB  - The headspace solid-phase microextraction (HS-SPME) of ethyl carbamate from
      alcoholic beverages was optimized for the first time using a face-centered cube
      central composite design (CCD). The factors expected to influence the extraction
      process are discussed. Firstly, some of factors are fixed based on the opinion of
      expert and previous experiments, which reduce the number of factors and then
      avoid very complex response models and large variability. Secondly, for three
      remaining inexplicit factors, sample temperature, pH and %NaCl, a face-centered
      cube central composite design was performed and a response surface equation was
      derived. The statistical parameters of the derived model were r=0.974 and
      F=20.183. The optimum conditions were obtained using a grid method. Next, the
      method was analytically evaluated using the optimum conditions. The detection
      limit, relative standard deviation, linear range and recovery were 3microgL(-1),
      4.3-8.6%, 10-160microgL(-1), and 92.8-97.5%, respectively. Finally, the method
      was applied to a variety of alcoholic beverages.

PMID- 18809076
TI  - Sensitive and stable monitoring of lead and cadmium in seawater using screen
      printed electrode and electrochemical stripping analysis.
AB  - Sensitive and stable monitoring of heavy metals in seawater using screen-printed
      electrodes (SPE) is presented. The analytical performance of SPE coupled with
      square wave anodic stripping voltammetry (SWASV) for the simultaneous
      determination of Pb and Cd in seawater samples, in the low microgL(-1) range, is
      evaluated. The stripping response for the heavy metals following 2min deposition
      was linear over the concentration range examined (10-2000microgL(-1)) with
      detection limits of 1.8 and 2.9microgL(-1) for Pb and Cd, respectively. The
      accuracy of the method was validated by analyzing metal contents in different
      spiked seawater samples and comparing these results to those obtained with the
      well-established anodic stripping voltammetry using the hanging mercury drop
      electrode. Moreover, a certified reference material was also used and the results
      obtained were satisfactory.

PMID- 18809077
TI  - Carboxyl modified multi-walled carbon nanotubes as solid-phase extraction
      adsorbents combined with high-performance liquid chromatography for analysis of
      linear alkylbenzene sulfonates.
AB  - Recently, multi-wall carbon nanotubes (MWCNTs) as adsorbents of solid-phase
      extraction are attractive because they can be used for enrichment of organic
      compounds and metal ions at trace levels. In this study, we use the carboxyl
      modified multi-wall carbon nanotubes (CMMWCNTs) as adsorbents of solid-phase
      extraction for extraction of linear alkylbenzene sulfonates (LAS), which are
      widely used anion surfactant with different homologues, and detected by HPLC-UV.
      The effect of eluent and its volume, sample pH and flow rate, sample volume and
      the ultrasonic time of sample, the content of the electrolyte (NaCl) were
      investigated and optimized. The detection limit for LAS homologues was 0.02
      0.03microgL(-1) with R.S.D. (n=6) ranging from 2.04 to 10.03%. The recoveries of
      LAS homologues in the spiked environmental water samples ranged from 84.8 to
      106.1%. The proposed method has been applied successfully to the analysis of LAS
      in aqueous environmental samples, which demonstrates that CMMWCNTs-based solid
      phase extraction is a precision and convenient enrichment method and can be used
      for analysis of LAS homologues in water samples.

PMID- 18809078
TI  - Flow injection conductometric system with gas diffusion separation for the
      determination of Kjeldahl nitrogen in milk and chicken meat.
AB  - A simple flow injection (FI) conductometric system with gas diffusion separation
      was developed for the determination of Kjeldahl nitrogen (or proteins) in milk
      and chicken meat. The sample was digested according to the Kjeldahl standard
      method and the digest was diluted and directly injected into the donor stream
      consisting of 4M NaOH. In alkaline medium, ammonium was converted to ammonia,
      which diffused through the PTFE membrane to dissolve in an acceptor stream
      (water). Dissociation of ammonia caused a change in conductance of the acceptor
      solution, which was linearly proportional to the concentration of ammonium
      originally present in the injected solution. A conductometric flow through cell
      and an amplifier circuit was fabricated, which helped improve sensitivity of the
      conductometric detection system. With using a plumbing Teflon tape as a gas
      diffusion membrane and without thermostating control of the system, a linear
      calibration graph in range of 10-100mgL(-1) N-NH(4) was obtained, with detection
      limit of 1mgL(-1) and good precision (relative standard deviation of 0.3% for 11
      replicate injections of 50mgL(-1) N-NH(4)). The developed method was validated by
      the standard Kjeldahl distillation/titration method for the analysis of milk and
      chicken meat samples. The proposed system had sample throughput of 35h(-1) and
      consumed much smaller amounts of chemical than the standard method (275mg vs
      17.5g of NaOH per analysis, respectively).

PMID- 18809079
TI  - Dependence of calibration sensitivity of a polysulfone/Ru(II)-tris(4,7-diphenyl
      1,10-phenanthroline)-based oxygen optical sensor on its structural parameters.
AB  - The optimum performance of an optical oxygen sensor based on polysulfone
      (PSF)/[Ru(II)-Tris(4,7-diphenyl-1,10-phenanthroline)] octylsulfonate (Ru(dpp)OS)
      was checked by carefully tuning the parameters affecting the membrane
      preparation. In particular, membranes having thickness ranging between 0.2 and
      8.0 microm with various luminophore concentrations were prepared by dip-coating
      and tested. The membrane thickness was controlled by tuning the solution
      viscosity, and was measured both by secondary ion mass spectrometry (SIMS) and by
      visible spectroscopy (Vis). Luminescence-quenching-based calibration was a single
      value of the Stern-Volmer constant (K'SV) for membranes containing up to 20 mmol
      Ru(dpp) g-1 PSF (1.35 microm average thickness). The K'SV value decreased for
      larger concentration. The highest sensitivity was obtained with membrane
      thickness around 1.6 microm, having a response time close to 1 s. Thicker
      membranes exhibited an emission saturation effect and were characterized by
      longer response time. The K'SV behavior was interpreted on the basis of a
      mathematical approach accounting for the contribution of luminescence lifetime
      (tau0), oxygen diffusion coefficient (DO2) and oxygen solubility inside the
      membrane (sO2) establishing the role of all of them and allowing their
      experimental determination. Moreover, a simple experimental way to estimate K'SV
      without needing calibration was proposed. It was based either on the light
      emission asymmetry or on the percent variation of light emission on passing from
      pure nitrogen to pure oxygen.

PMID- 18809080
TI  - Optochemical sensing of hydrogen chloride gas using meso-tetramesitylporphyrin
      deposited glass plate.
AB  - Meso-tetramesitylporphyrin (MTMP) deposited glass plate (solid state sensor) was
      used to sense hydrogen chloride (HCl) gas based on optochemical method. Exposure
      of the solid state sensor to HCl vapor results in the formation of protonated
      meso-tetramesitylporphyrin (PMTMP). UV-vis and fluorescence spectral techniques
      were used to study the protonation of MTMP in dichloromethane-methanol mixture.
      The optical spectra of MTMP show an intense Soret band at 418nm with a 14nm red
      shift upon protonation by HCl. Ab-initio calculations were carried out to
      visualize the effect of protonation on planarity and stability of the porphyrin
      ring. The solid state sensor was characterized by UV-vis spectral technique. The
      sensor exhibits characteristic Soret and Q bands for the deposited MTMP with
      slight red shift when compared to MTMP in dichloromethane. The concentration of
      gaseous HCl was monitored from the changes in the absorbance of Soret band of
      PMTMP at 452nm. The detection limit of the solid state sensor towards gaseous HCl
      was found to be 0.03ppm. The present solid state sensor was highly stable for
      several months.

PMID- 18809081
TI  - A selective colorimetric chemosensor for thiols based on intramolecular charge
      transfer mechanism.
AB  - Compound 1 as an electron donor-acceptor compound with N,N-dimethylaniline and
      quinone units was designed for a highly selective colorimetric determination of
      thiol-containing amino acids and peptides, by making use of the unique reactivity
      of thiol towards quinone. Compound 1 shows a strong intramolecular charge
      transfer (ICT) band around 582nm; but, it decreased after addition of either
      cysteine (Cys) or glutathione (GSH). Moreover, the ICT band intensity at 582nm
      decreased linearly with the increasing concentrations of Cys or GSH. The
      interference from other amino acids can be neglected. Therefore, compound 1 can
      be employed as a selective colorimetric visual chemosensor for thiol-containing
      amino acids and peptides.

PMID- 18809082
TI  - Speciation analysis of selected metals and determination of their total contents
      in paired serum and cerebrospinal fluid samples: An approach to investigate the
      permeability of the human blood-cerebrospinal fluid-barrier.
AB  - Neurodegenerative diseases like Alzheimer's disease and Parkinson's disease are
      gaining increasing relevance in our aging society. However, the complex
      multifactorial mechanisms of these diseases are not sufficiently understood yet.
      Several studies indicate that metal ions play an important role in the promotion
      of these diseases. Consequently, the transport pathways of metals and their
      species to the brain are of special interest. Following oral or inhalative uptake
      metals are absorbed and distributed via the blood stream in the body. Transport
      into the brain requires crossing of the neural barriers. Our study focuses on the
      investigation of the permeability of the blood-cerebrospinal fluid (CSF)-barrier
      for selected metals (Mn, Fe, Cu, Zn, Mg and Ca). For the first time paired human
      serum and CSF samples obtained from a neurological department were characterised
      for total metal concentrations and metal species. For CSF few data are available
      in the literature on total metal contents and applications of element speciation
      analysis in CSF samples are rare. In our study mean CSF/serum ratios (n=29) were
      0.7 for Mn, 0.02 for Fe, 0.02 for Cu, 0.03 for Zn, 1.3 for Mg and 0.5 for Ca.
      Size exclusion chromatography (SEC) online with inductively coupled plasma mass
      spectrometry was further developed for the size characterisation of the metal
      species in CSF and serum with limits of detection of 0.4microgL(-1) for Fe,
      0.01microgL(-1) for Mn, 0.2microgL(-1) for Cu, 0.2microgL(-1) for Zn, 0.6microgL(
      1) for Mg and 3.8microgL(-1) for Ca in the eluate from the HPLC column. Apart
      from Mn the application of this technique has not been published for metal
      speciation in CSF, yet. In the case of some Mn species it turned out that
      methanol, which was contained in the mobile phase of a SEC method previously
      published from our group on qualitative characterisation of Mn species, was
      interfering with the quantification. The modified method developed in this work
      (with NaCl but without methanol in the mobile phase; use of internal standard)
      allowed reliable quantification. The results clearly indicate changes in the
      metal species pattern due to different permeation behaviour at the blood-CSF
      barrier. As part of the method validation the relative stability of complexes of
      albumin, transferrin and citrate with Mn, Fe, Cu and Zn was investigated.

PMID- 18809083
TI  - Application of Fenton reaction for nanomolar determination of hydrogen peroxide
      in seawater.
AB  - A simple and sensitive method for the determination of nanomolar levels of
      hydrogen peroxide (H(2)O(2)) in seawater has been developed and validated. This
      method is based on the reduction of H(2)O(2) by ferrous iron in acid solution to
      yield hydroxyl radical (OH) which reacts with benzene to produce phenol. Phenol
      is separated from the reaction mixture by reversed phase high performance liquid
      chromatography and its fluorescence intensity signals were measured at excitation
      and emission of 270 and 298nm, respectively. Under optimum conditions, the
      calibration curve exhibited linearity in the range of (0-50)x10(3)nmolL(-1)
      H(2)O(2). The relative standard deviations for five replicate measurements of 500
      and 50nmolL(-1) H(2)O(2) are 1.9 and 2.4%, respectively. The detection limit for
      H(2)O(2), defined as three times the standard deviation of the lowest standard
      solution (5nmolL(-1) H(2)O(2)) in seawater is 4nmolL(-1). Interference of nitrite
      ion (NO(2)(-)) on the fluorescence intensity of phenol was also investigated. The
      result indicated that the addition of 10micromolL(-1) NO(2)(-) to seawater
      samples showed no significant interference, although, the addition of
      50micromolL(-1) NO(2)(-) to the seawater samples decreases the fluorescence
      intensity signals of phenol by almost 40%. Intercomparison of this method with
      well-accepted (p-hydroxyphenyl) acetic acid (POHPAA)-FIA method shows excellent
      agreement. The proposed method has been applied on-board analysis of H(2)O(2) in
      Seto Inland seawater samples.

PMID- 18809084
TI  - Determination of estradiol in human serum using magnetic particles-based
      chemiluminescence immunoassay.
AB  - A magnetic particles (MPs)-based chemiluminescence immunoassay (CLIA) with high
      sensitivity, specificity, and reproducibility was proposed for the evaluation of
      estradiol (E(2)) in human sera. The MPs coated with secondary antibody were used
      as dispersed solid phase for the immunoassay, and the horseradish peroxidase
      (HRP)-luminol-H(2)O(2) chemiluminescent system with high sensitivity was chosen
      as the detection system. The method showed specific recognition to E(2), without
      cross-reaction for the major steroids, including estrone (E(1)), estriol (E(3)),
      dihydrotestosterone (DHT), androstenedione, and testosterone (T), which was
      commonly found in human serum. The addition of sodium trichloracetate (Na-TCA) in
      the enzyme buffer as a blocking agent contributed to the realization of direct
      analysis of E(2) in human serum without extraction. Besides, the effects of
      several physicochemical parameters, including the dilution ratios of E(2)-6-HRP
      conjugate and anti-E(2) polyclonal antibody, immunoreaction time,
      chemiluminescent (CL) substrate volume, volume of MPs, and CL reaction time, were
      studied and optimized. The proposed method had a detection limit of 2.51pgmL(-1)
      with a larger working range of 15-1000pgmL(-1). The inter-assay and intra-assay
      coefficient of variation (CV) were both less than 15%. The average recoveries of
      three different spiked concentration samples were 93.3, 106 and 101%,
      respectively. The method has been successfully applied to the determination of
      E(2) in 105 human sera and showed a good correlation compared with the commercial
      radioimmunoassay (RIA) kit with a correlative coefficient of 0.9892. This method
      has exhibited great potential in the fabrication of diagnostic kit and could be
      used in the clinical analysis of E(2) in human serum.

PMID- 18809085
TI  - Foreword. Surgical aspects of tuberculosis.

PMID- 18809086
TI  - In brief. Historical indications for the surgical treatment of tuberculosis.

PMID- 18809087
TI  - Surgical aspects of thoracic tuberculosis: a contemporary review--part 2.

PMID- 18809089
TI  - Anemia in the elderly: introduction.

PMID- 18809091
TI  - Hematopoietic stem cells and the aging hematopoietic system.
AB  - The etiology of the age-associated pathophysiological changes of the
      hematopoietic system including the onset of anemia, diminished adaptive immune
      competence, and myelogenous disease development are underwritten by the loss of
      normal homeostatic control. As tissue and organ homeostasis in adults is
      primarily mediated by the activity of stem and progenitor cells, it has been
      suggested that the imbalances accompanying aging of the hematopoietic system may
      stem from alterations in the prevalence and/or functional capacity of
      hematopoietic stem cells (HSCs) and progenitors. In this review, we examine
      evidence implicating a role for stem cells in the aging of the hematopoietic
      system, and focus on the mechanisms suggested to contribute to stem cell aging.

PMID- 18809090
TI  - Epidemiology of anemia in older adults.
AB  - Anemia is a common, multifactorial condition among older adults. The World Health
      Organization (WHO) definition of anemia (hemoglobin concentration <12 g/dL in
      women and <13 g/dL in men) is most often used in epidemiologic studies of older
      adults. More than 10% of community-dwelling adults age 65 years and older has WHO
      defined anemia. After age 50 years, prevalence of anemia increases with advancing
      age and exceeds 20% in those 85 years and older. In nursing homes, anemia is
      present in 48% to 63% of residents. Incidence of anemia in older adults is not
      well characterized. Among older adults with anemia, approximately one third have
      evidence of iron, folate, and/or vitamin B(12) deficiency, another third have
      renal insufficiency and/or chronic inflammation, and the remaining third have
      anemia that is unexplained. Several studies demonstrate that anemia is associated
      with poorer survival in older adults. This review details the distribution and
      consequences of anemia in older adults and identifies future epidemiologic
      research needs.

PMID- 18809092
TI  - Nutritional anemias and the elderly.
AB  - Nutritional anemias are important because they are easily reversed and because
      their underlying causes, most often unrelated to dietary intake, require
      individualized assessment. Iron-deficiency anemia (IDA) usually results from iron
      losses accompanying chronic bleeding, including loss to intestinal parasites, or
      from gastric disorders or malabsorption in the elderly. Cobalamin-deficiency
      anemia, the only nutritional anemia with predilection for the elderly, nearly
      always stems from failure of intrinsic factor (IF)-related absorption. Folate
      deficiency anemia, the only nutritional anemia usually caused by poor intake, has
      nearly disappeared in countries that fortify food with folic acid. Copper
      deficiency anemia, which usually results from malabsorptive disorders or from
      medical or nutritional interventions that provide inadequate copper or excess
      zinc, is uncommon but increasingly recognized. The prevalences of nutritional
      anemias, which are not always distinguished from non-anemic deficiency, are
      uncertain. The mean corpuscular volume (MCV) provides an essential diagnostic
      tool leading to judicious matching of relevant biochemical changes with relevant
      anemia. Nutritional anemias usually feature abnormal MCV, whereas the predominant
      anemias in the aged, especially the anemias of chronic disease/chronic
      inflammation (ACD/ACI), of renal failure, and of unknown causes, are typically
      normocytic.

PMID- 18809093
TI  - Renal disease and anemia in the elderly.
AB  - As individuals age, the incidence of both renal insufficiency and anemia
      increases. Some of the changes in renal function can be traced to age-related
      alterations in the renal vasculature that may dissociate renal blood flow from
      glomerular filtration. In addition, there appear to be paradoxical changes in
      renal production of erythropoietin (Epo), in that Epo levels actually increase
      over time with aging, suggesting that the erythroid marrow may become less
      sensitive to Epo stimulation. These factors, together with the confounding
      effects of possible nutritional deficits and the disproportionate effect of early
      stage diabetes mellitus on renal endocrine function and Epo production, all can
      contribute to anemia in the elderly. As anemia is an independent predictor of
      poor outcomes with many diseases and at any age, recognizing and correcting the
      underlying cause of the anemia is an important aspect of medically managing the
      elderly patient.

PMID- 18809094
TI  - Anemia of aging: the role of chronic inflammation and cancer.
AB  - Aging is associated with increased incidence and prevalence of anemia, leading to
      a number of adverse health outcomes. These include death, functional dependence,
      increased risk of therapeutic complications, falls, and dementia. In
      approximately 30% of cases, anemia in older individuals is due to either relative
      or absolute erythropoietin (EPO) deficiency. Absolute EPO deficiency may be
      primary or secondary to declining renal function. Relative EPO deficiency is due
      to an age-related pro-inflammatory status that reduces the sensitivity of
      erythropoietic precursors to EPO. Despite this condition of EPO deficiency, the
      management of anemia of aging with erythropoiesis-stimulating agents (ESAs) is
      controversial, unless the anemia is due to renal insufficiency. The main concern
      related to this treatment arises from eight studies of ESAs in cancer, suggesting
      that ESAs may reduce patient survival in addition to increasing the risk of deep
      vein thrombosis. The results of these studies contrast with a host of other
      trials showing the safety of ESAs. The discrepancy may be explained in part by
      the fact that, in the trials suggesting a detrimental effect of ESAs, the goal
      was to obtain hemoglobin (Hb) levels higher than 12 g/dL. Because of this
      concern, correction of anemia in elderly individuals with relative EPO
      insufficiency should not be attempted outside clinical trials.

PMID- 18809095
TI  - Unexplained anemia in the elderly.
AB  - Among the elderly, anemia occurs with increasing frequency with each advancing
      decade. Unlike when anemia occurs in younger adults, the cause of anemia in the
      elderly is oftentimes not readily apparent or attributable to a single cause.
      However, this commonly observed form of anemia in the elderly (termed unexplained
      anemia [UA]) can generally be dissected to its root causes, which include renal
      insufficiency, inflammation, testosterone deficiency, and stem cell proliferative
      decline. Myelodysplasia (MDS) occurs commonly in this age group but can and
      should, for both diagnostic and therapeutic considerations, be distinguished from
      UA.

PMID- 18809096
TI  - Functional outcomes of anemia in older adults.
AB  - Observational studies have consistently documented independent, strong
      associations of anemia--even if not severe--with major adverse functional
      outcomes in older adults. In this chapter, recent epidemiologic evidence linking
      mild anemia with decline in physical and cognitive function, frailty, and
      disability in community-dwelling older adults is reviewed. Altogether, these
      biologically plausible associations provide empirical, though not conclusive,
      support for the notion of mild anemia as a cause of adverse functional outcomes
      in older adults. Randomized clinical trial data assessing the impact of anemia
      correction on functional outcomes are lacking at this time.

PMID- 18809097
TI  - Anemia and the frail elderly.
AB  - Frailty engenders a recognizable clinical syndrome of vulnerability to stressors
      related to impaired physiologic reserve that primarily occurs among older adults.
      Features of frailty include weight loss, exhaustion, muscle weakness, performance
      impairment, and cognitive slowing and can be identified independent of comorbid
      conditions. Among frail older adults, anemia prevalence is markedly increased.
      The interaction between anemia and frailty is complex and confidently separating
      cause and effect may not be possible. Nevertheless, anemia functions as a
      powerful prognostic factor for the development of frailty related problems such
      as muscle weakness, reduced performance, falls, and mortality. Further, mildly
      reduced hemoglobin shows a similar association with adverse outcomes. The data
      strongly intimate that anemia predisposes or accelerates the development of
      frailty. Anemia interventional studies are sorely needed to determine whether
      treatment may mitigate either the development of frailty and/or the sequela of
      frailty.

PMID- 18809099
TI  - On turning 40.

PMID- 18809100
TI  - Work hard. Have fun. Overachieve.

PMID- 18809101
TI  - The specialty of emergency medicine: needed now more than ever before.

PMID- 18809098
TI  - Erythropoietic agents and the elderly.
AB  - Erythropoietin (Epo) is a peptide hormone that stimulates erythropoiesis. There
      are several agents in clinical use and in development that either act as ligands
      for the cell surface receptors of Epo or promote Epo production, which stimulates
      erythropoiesis. These are known as erythropoietic agents. The agents already in
      use include epoetin alfa, epoetin beta, and darbepoetin alfa. Newer agents under
      active investigation include continuous erythropoietin receptor activator (CERA)
      or proline hydroxylase inhibitors that increase hypoxia-inducible factor-1 (HIF
      1), thereby stimulating Epo production and iron availability and supply.
      Erythropoietic agents have been shown to promote neuronal regeneration and to
      decrease post-stroke infarct size in mouse models. They have also been reported
      to shorten survival when used to treat anemia in many cancer patients and to
      increase thromboembolism. In contrast, rapid decrease of Epo levels as observed
      in astronauts and high-altitude dwellers upon rapid descent to sea level leads to
      the decrease of erythroid mass, a phenomenon known as "neocytolysis." The
      relative decrease in the serum Epo level is known to occur in some subjects with
      otherwise unexplained anemia of aging. Anemia by itself is a predictor of poor
      physical function in the elderly and is a significant economic burden on society.
      One out of every five persons in the United States will be elderly by 2050.
      Erythropoietic agents, by preventing and treating otherwise unexplained anemias
      of the elderly and anemia associated with other disease conditions of the
      elderly, have the potential to improve the functional capacity and to decrease
      the morbidity and mortality in the elderly, thereby alleviating the overall
      burden of medical care in society.

PMID- 18809102
TI  - Looking back ahead.

PMID- 18809103
TI  - Proptosis of left eye: frontoethmoid mucocele.

PMID- 18809104
TI  - Right eye swelling: orbital blowout fracture.

PMID- 18809105
TI  - Clinical policy: critical issues in the evaluation and management of adult
      patients presenting to the emergency department with acute headache.
AB  - This clinical policy from the American College of Emergency Physicians is an
      update of a 2002 clinical policy on the evaluation and management of adult
      patients presenting to the emergency department (ED) with acute, nontraumatic
      headache. A writing subcommittee reviewed the literature to derive evidence-based
      recommendations to help clinicians answer the following 5 critical questions: (1)
      Does a response to therapy predict the etiology of an acute headache? (2) Which
      patients with headache require neuroimaging in the ED? (3) Does lumbar puncture
      need to be routinely performed on ED patients being worked up for nontraumatic
      subarachnoid hemorrhage whose noncontrast brain computed tomography (CT) scans
      are interpreted as normal? (4) In which adult patients with a complaint of
      headache can a lumbar puncture be safely performed without a neuroimaging study?
      (5) Is there a need for further emergent diagnostic imaging in the patient with
      sudden-onset, severe headache who has negative findings in both CT and lumbar
      puncture? Evidence was graded and recommendations were given based on the
      strength of the available data in the medical literature.

PMID- 18809106
TI  - Commentary: emergency medical services: just the beginning of an effective
      system.

PMID- 18809108
TI  - Annals of Emergency Medicine Journal Club. Acutely decompensated heart failure in
      a county emergency department: a double-blind randomized controlled comparison of
      nesiritide versus placebo treatment. Answers to May 2008 journal club questions.

PMID- 18809109
TI  - Eye pain and double vision: superior orbital wall fracture with retro-orbital
      hematoma.

PMID- 18809110
TI  - Elderly woman with eye pain: Ectopia lentis.

PMID- 18809111
TI  - Ultrasound-guided axillary vein approach to the subclavian vein for central
      venous access.

PMID- 18809112
TI  - Ciguatera poisoning successfully treated with delayed mannitol.

PMID- 18809113
TI  - Standardization of product concentration in emergency dosing: a response to
      Fineberg and Arendt.

PMID- 18809115
TI  - Hypoxemia after total joint arthroplasty: a problem on the rise.
AB  - Total joint arthroplasty (TJA) is categorized as a major risk factor for
      thromboembolic complications. The importance of hypoxemia during the
      postoperative period is subject of controversy. This prospective study elucidates
      the incidence and etiology of hypoxemia after TJA. Furthermore, we intended to
      assess the predictive value of clinical findings in identifying the etiology of
      hypoxemia after TJA. Of 1971 patients, 78 (4.0%) experienced an acute episode of
      hypoxemia during their hospitalization after TJA. Hypoxemia as the initial
      presenting sign, predicted major complications, defined as life-threatening if
      left untreated, in 32% of the hypoxic population. These diagnoses included
      pulmonary embolism, pulmonary edema, and pneumonia. Tachypnea was the only
      independent factor associated with pulmonary embolism. Our study presents the
      incidence and etiology of hypoxemia after TJA, and we recommend a heightened
      appreciation for the hypoxemic patient.

PMID- 18809117
TI  - Coping styles of outpatients with a bipolar disorder.
AB  - Patients with a bipolar disorder need to cope with the problems they encounter,
      the consequences of their disease, and unpleasant events to stay well. This study
      was undertaken to gain greater insight into the coping styles of outpatients with
      a bipolar disorder when confronted with problems and unpleasant events. The
      participants (N = 157) completed the Utrecht Coping List and a questionnaire
      addressing various demographic and clinical characteristics. The results showed
      outpatients with a bipolar disorder to have a less active reaction pattern and a
      more avoidant coping style compared with people from the general population.

PMID- 18809118
TI  - Associations between psychiatric disorders and menstrual cycle characteristics.
AB  - An understanding of the relationship between psychiatric disorders and menstrual
      characteristics is important to the assessment and care of women. Menstrual cycle
      regularity and length have significant associations with specific current and
      lifetime psychiatric disorders. The purpose of this study was to investigate
      whether psychiatric disorders are associated with menstrual cycle length or
      regularity. The sample included 628 pregnant Medicaid-eligible women from Women,
      Infants, and Children's Supplemental Nutrition Program sites in five counties in
      rural Missouri and the city of St. Louis. Women were assessed for current (12
      month) and lifetime psychiatric disorders with the Diagnostic Interview Schedule
      IV. Menstrual length and regularity were assessed by self-report. Analyses
      consisted of logistic regression while controlling for race. Independent of the
      effects of race, (a) women who reported irregular cycles were less than half as
      likely to have a current anxiety disorder as those that reported regular cycles,
      and (b) women with shorter cycles (<or=28 days) have one and a half times to two
      times greater risk of current affective disorder, lifetime affective disorder,
      lifetime anxiety disorder, lifetime substance use or dependence disorder, and
      lifetime drug abuse or dependence. A significant interaction effect for race and
      cycle length indicated that cycle length predicted likelihood of having any
      lifetime psychiatric disorder for Caucasians only and there was no association
      between cycle length and lifetime psychiatric diagnosis for African American
      women.

PMID- 18809119
TI  - A qualitative inquiry into the Taiwanese mentally ill persons' difficulties
      living in the community.
AB  - Community care has been a paradigm shift for psychiatric treatment worldwide;
      however, it has not been successfully implemented in many developing countries,
      including Taiwan. This qualitative study aimed to explore the Taiwanese mentally
      ill persons' difficulties living in the community. Social disadvantages and
      illness adaptation were recognized as two domains of difficulties encountered by
      Taiwanese mentally ill patients living in the community, while six themes were
      identified: getting a "shameful" illness, unmet needs for community care, being
      overcome by a distorted world, denying the illness, living with the illness, and
      adapting to changed level of functioning. Related cultural issues were also
      discussed.

PMID- 18809120
TI  - Institutional therapeutic alliance and its relationship with outcomes in a
      psychiatric day hospital program.
AB  - The article shows the results of a longitudinal study aimed to explore the
      institutional therapeutic alliance (ITA) that is the alliance formed by a patient
      and all the therapeutic staff. Fifty five patients who have psychiatric disorders
      in partial hospitalization were evaluated at admission (global functional level,
      social support, symptomatic condition, and treatment expectancies), at discharge,
      and after 3 months. ITA was assessed after 1 week of treatment and at discharge,
      from patient's and staff's perspectives. Preliminary findings suggest that the
      ITA represents a specific phenomenon different from the classical therapeutic
      alliance (patienttherapist), which would be particularly relevant for the
      treatment of patients who are severely disturbed.

PMID- 18809121
TI  - Do attention deficit/hyperactivity disorder and oppositional defiant disorder
      influence preschool unintentional injury risk?
AB  - PURPOSE: This study explores the relationship among preschool attention
      deficit/hyperactivity disorder (ADHD), oppositional defiant disorder (ODD),
      injury-risk-taking behavior, and unintentional injury. METHOD: An emergency
      department (ED) casecontrol study of parent-reported child behavior was
      conducted. FINDINGS: Children with ODD and ADHD had significantly more injury
      risk-taking behaviors (odds ratio [OR] = 7.68, 95% confidence interval [CI] 2.25
      26.25; OR = 4.87, 95% CI 1.17--20.28, respectively), and injured children had a
      17-fold increase in high-risk-taking behaviors (OR 17.2, 95% CI 2.14--138.0). No
      significant association existed between ODD or ADHD and ED-treated unintentional
      injury. IMPLICATIONS: Disruptive behavior disorders are not major contributors to
      ED-treated unintentional injury in preschool children.

PMID- 18809122
TI  - Smoking cessation and serious mental illness.
AB  - A focus group methodology was employed to identify personal, social, and
      environmental factors that affect smoking cessation in persons with serious
      mental illness. Four focus groups were held: two for those who had attempted to
      quit smoking and two for those who had never attempted to quit. Smoking is
      central to daily survival in patients with serious mental illness. Social and
      environmental reinforcement can both assist and hinder efforts to stop smoking.
      Smoke-free environments influence decisions to quit smoking if positive social
      comparisons with nonsmokers occur. Peer modeling and interpersonal connections
      with nonsmokers can offer links to forming supportive nonsmoking relationships.

PMID- 18809123
TI  - Efficacy of omega-3 fatty acid supplementation on improvement of bipolar
      symptoms: a systematic review.
AB  - The purpose of this review was to examine the current level of evidence regarding
      the efficacy of omega-3 fatty acid supplementation in improving bipolar disorder
      symptoms. Of 99 articles meeting initial search criteria, 5 randomized control
      trials and 2 quasi-experimental studies were selected for review. Omega-3 fatty
      acid supplementation was effective in 4 of 7 studies. Those using an omega-3
      combination of eicosapentaenoic acid and docosahexanoic acid demonstrated a
      statistically significant improvement in bipolar symptoms, whereas those using a
      single constituent did not. Dosage variations did not demonstrate statistically
      significant differences. Due to its benign side effect profile and some evidence
      supporting its usefulness in bipolar illness, omega-3 may be a helpful adjunct in
      treatment of selected patients. Future studies are needed to conclusively confirm
      the efficacy of omega-3s in bipolar disorder, uncovering a new well-tolerated
      treatment option.

PMID- 18809124
TI  - Psychological consequences of human rights abuses: how can psychiatric nurses
      respond?

PMID- 18809125
TI  - Veterans reported reasons for seeking mental health treatment.

PMID- 18809126
TI  - Can we afford to be complacent about teens' use of condoms?

PMID- 18809127
TI  - Pushing secondhand smoke and the tobacco industry outside the social norm to
      reduce adolescent smoking.

PMID- 18809128
TI  - Teenagers and cosmetic surgery: focus on breast augmentation and liposuction.
AB  - Two of the most popular and controversial cosmetic procedures for adolescents are
      liposuction and breast implants. In this review article, the procedures are
      discussed. In addition, the physiological and psychological reasons to delay
      these procedures, including concerns about body dysmorphic disorder and research
      findings regarding changes in teenagers' body image as they mature, are
      described. The lack of persuasive empirical research on the mental health
      benefits of plastic surgery for teenagers is highlighted. Finally, the long-term
      financial and health implications of implanted medical devices with a limited
      lifespan are presented. Adolescent medicine providers need to be involved in
      improving informed decision making for these procedures, aware of the absence of
      data on the health and mental health risks and benefits of these surgeries for
      teenagers, and understand the limitations on teenagers' abilities to evaluate
      risks.

PMID- 18809129
TI  - Condom use and consistency among male adolescents in the United States.
AB  - PURPOSE: To incorporate a behavioral model of health services utilization to
      examine whether male adolescents' family, individual, sex education, and partner
      factors are associated with several measures of condom use and consistency in
      heterosexual relationships. METHODS: We examine a sample of sexually experienced
      male adolescents 15-19 years of age in the 2002 National Survey of Family Growth
      (NSFG) to identify factors associated with condom use at first sex and last sex,
      condom consistency with their most recent sexual partner, and condom consistency
      in the past 4 weeks. RESULTS: Male adolescents who were Hispanic and those who
      did not receive formal sex education had lower odds of condom use and/or
      consistency, whereas African-American male adolescents and those with more
      positive attitudes about condoms had greater odds. Males who were older at most
      recent sex, who had an older sexual partner or a casual first sexual partner, who
      had a partner who used a method of contraception, who were in longer
      relationships, or who engaged in more frequent sex had reduced odds of
      contraceptive use. CONCLUSIONS: Findings highlight multiple domains of influence
      on condom use behaviors among male adolescents. Programs that provide targeted
      services, address condom use attitudes, and help teens to negotiate condom use
      decision making with sexual partners may help to reduce high rates of sexually
      transmitted infections among male adolescents in the United States.

PMID- 18809130
TI  - Adolescent smoking trajectories: results from a population-based cohort study.
AB  - PURPOSE: To identify distinct smoking trajectories during adolescence and assess
      how smoking-related factors relate to trajectory membership. METHODS: The sample
      includes 3637 youth from across the state of Minnesota. Measures include tobacco
      use, smoking behaviors of parents and friends, youth smoking-related attitudes
      and beliefs, and home smoking policies. A cohort-sequential design was used to
      identify smoking trajectories, including five cohorts of youth (ages 12-16)
      followed for 3 years. RESULTS: Six distinct trajectories of tobacco use were
      found: nonsmokers (54%), triers (17%), occasional users (10%), early established
      (7%), late established (8%), and decliners (4%). Several factors were associated
      with increased likelihood of being in a smoking trajectory group (vs. the
      nonsmoking group): parental smoking, friend smoking, greater perceptions of the
      number of adults and teenagers who smoke, and higher functional meaning of
      tobacco use. In contrast, higher perceived difficulty smoking in public places,
      negative perceptions of the tobacco industry, and home smoking policies were
      associated with less likelihood of being in one of the smoking trajectories (vs.
      the nonsmoking trajectory). CONCLUSIONS: Adolescents exhibit diverse patterns of
      smoking during adolescence and tobacco-related influences were strong predictors
      of trajectory membership.

PMID- 18809131
TI  - Virginity pledges among the willing: delays in first intercourse and consistency
      of condom use.
AB  - PURPOSE: We examine longitudinal relationships between virginity pledging in
      adolescence and both sexual initiation and condom use. Prior studies have had
      mixed results and may not adequately control for prepledge differences between
      pledgers and nonpledgers. METHODS: Data came from a national sample of 12- to 17
      year-olds surveyed in 2001 and reinterviewed 1 and 3 years later. Logistic
      regression models estimated the association between making a pledge and each
      outcome. Selection bias was reduced through propensity-score weighting and a rich
      set of demographic and psychosocial covariates. RESULTS: Pledgers and nonpledgers
      differed substantially in preexisting characteristics. However, after propensity
      weighting and statistical controls, pledging was still associated with delayed
      intercourse. We estimate that in the absence of pledging 42.4% of virgins with
      characteristics indicating an inclination to pledge initiate intercourse within 3
      years; in the presence of the pledge, 33.6% of such youth initiate intercourse.
      Among those who had sex during this period, pledging was unassociated with condom
      use. Among those who did not have sex during this period, pledging was
      unassociated with engagement in noncoital sexual behavior. CONCLUSIONS: Making a
      virginity pledge appears to be an effective means of delaying sexual intercourse
      initiation among those inclined to pledge without influencing other sexual
      behavior; pledging does not appear to affect sexual safety among pledgers who
      fail to remain abstinent.

PMID- 18809132
TI  - Vaginal microbicide preferences among midwestern urban adolescent women.
AB  - PURPOSE: The purpose of this study was to assess adolescent women's preferences
      for specific microbicide characteristics including pregnancy prevention, timing
      of application, potential for side effects, and whether it targeted human
      immunodeficiency virus (HIV) or other sexually transmitted infections (STI).
      Potential differences in microbicide preferences by adolescent age group and
      behavioral patterns including engaging in sexual intercourse and use of hormonal
      contraception were examined, as it was hypothesized that as adolescents progress
      into adulthood and gain sexual experience their preferences in microbicide
      characteristics may shift. METHOD: Adolescent and young women (N = 405, 56.0%
      African American; 24.0% Euro-American) between the ages of 14 and 20 (mean =
      17.0, SD = 1.8) were recruited from urban community-based clinics. Video-Audio
      Computer-Assisted Self-Interviews were conducted with the young women, during
      which they were asked about their preferences regarding the characteristics of
      hypothetical vaginal microbicides. Conjoint analysis was utilized to determine
      adolescent women's relative preferences for each microbicide characteristic and
      intent-to-purchase microbicides based upon a combination of the selected
      properties. RESULTS: Overall, the results suggest adolescent and young women had
      an ordered preference for a microbicide with (1) no side effects, (2) pregnancy
      prevention, (3) postcoital application, and (4) protection against HIV. Age and
      behavioral group conjoint analyses resulted in the same pattern of preferences as
      those reported for the entire group. However, women having sex and not using
      hormonal contraception had a stronger preference for postcoital application.
      CONCLUSION: The findings suggest that young women's ratings of microbicides were
      sensitive to characteristics such as side effects, pregnancy prevention, and
      timing of application and should be considered in microbicide development. The
      conjoint analysis approach is useful in understanding microbicide preferences,
      and should be utilized with other populations to assess preferences for specific
      microbicide characteristics.

PMID- 18809133
TI  - Why do young women continue to have sexual intercourse despite pain?
AB  - PURPOSE: Many young women suffer from pain and discomfort during sexual
      intercourse, and an increasing number of them seek help for their problems. It
      seems that some young women continue to have sexual intercourse despite pain.
      However, their motives are unclear. METHODS: A total of 16 women, aged 14 to 20
      years, with variable degrees of coital pain were selected at a youth center in a
      city in southeastern Sweden, to explore why they continued to have sexual
      intercourse despite pain. The women participated in audiotaped qualitative
      individual interviews, which were analyzed using the constant comparative method
      from grounded theory. RESULTS: During the analysis we identified the core
      category striving to be affirmed in their image of an ideal woman and the
      categories resignation, sacrifice, and feeling guilt. The perceived ideal women
      had several distinct characteristics, such as willingness to have sexual
      intercourse, being perceptive of their partner's sexual needs, and being able to
      satisfy their partners. Having sexual intercourse per se was considered to be an
      affirmation of being a normal woman, irrespective of pain or discomfort.
      CONCLUSIONS: These young women's focus on a constructed ideal explains why they
      continue to have sexual intercourse despite pain. Greater awareness of these
      beliefs among gynecologists, sexologists, and other healthcare professionals
      involved in the management of young women with coital pain would be beneficial.

PMID- 18809134
TI  - Is there a trend of increased unwanted childbearing among young women in the
      United States?
AB  - PURPOSE: The majority of births to young women are unintended (either mistimed or
      unwanted), bearing an increased risk of poor health outcomes for both mother and
      child. In this analysis, we describe trends of unwanted, mistimed, and intended
      births reported by all women and specifically by young women in the National
      Survey of Family Growth (NSFG). METHODS: Using data from the 1982, 1988, 1995,
      and 2002 NSFG surveys, we calculated the proportion of unwanted, mistimed, and
      intended births by maternal age at birth. For the 1995 and 2002 NSFG surveys, we
      also assessed birth intentions among 15-24-year-old nulliparous women and the
      mean number of unwanted births in the past 5 years among all 15-24-year-old
      women. RESULTS: The proportion of unintended births decreased between 1988 and
      1995 but increased between 1995 and 2002. This recent increase was attributed to
      the increased proportion of unwanted births reported by women <25 years of age
      from 10.4% in 1995 to 18.6% in 2002 (p < .01). Between 1995 and 2002, the
      proportion of 15-24-year-old nulliparous women who intended no future births
      increased from 8.1% to 10.4% (p < .05), and the mean number of unwanted births
      per 1000 women aged 15-24 years increased from 25 to 48 (p < .01). CONCLUSIONS:
      Our analyses suggest an increasing trend in unwanted childbearing among young
      women between 1995 and 2002. Further research is needed to understand the meaning
      and causes of increased unwanted childbearing among young women and to identify
      characteristics of those at risk.

PMID- 18809135
TI  - The relationship between Spanish language use and substance use behaviors among
      Latino youth: a social network approach.
AB  - PURPOSE: Greater acculturation is associated with higher rates of substance use
      among Latino adolescents, but the reasons are poorly understood. One potential
      explanation is that social networks change with acculturation, leading to
      decreased protection and increased risk. Our objective was to identify Spanish
      language-sensitive individual and social network attributes associated with
      substance use in Latino adolescents. METHODS: Latino eighth-grade students in a
      Los Angeles public middle school completed a computerized, self-administered
      survey about tobacco, alcohol, drug use, and parental monitoring; and description
      of 30 social network members. Regression analyses were used to estimate the
      independent associations of network-level Spanish language use and other factors
      with a substance use behavior scale. Mediation analysis identified Spanish
      language-sensitive attributes. RESULTS: Network-level Spanish language use was
      associated with a substance use scale in bivariate but not multivariate models.
      Protective Spanish language-sensitive attributes included greater numbers of
      extended family members in the network, less substance use among network members,
      and greater perceived parental monitoring. Risky Spanish language-insensitive
      attributes include more high school aged network members. CONCLUSIONS: These
      results suggest that parental monitoring and some characteristics of social
      networks account for the relationship between Spanish language use and substance
      use among Latino adolescents. Clinic- or community-based interventions that
      enhance protective characteristics of social networks in Latino adolescents may
      be effective.

PMID- 18809136
TI  - Longitudinal associations between community violence exposure and suicidality.
AB  - PURPOSE: To examine longitudinal associations between community violence exposure
      and suicide ideation and attempt, and whether depressive symptoms and aggressive
      behavior are intervening variables in this association. METHODS: Participants
      were 473 urban and predominantly African American adolescents who completed
      measures of community violence exposure, depressive symptoms, and suicide
      ideation and attempt in grades 6, 7, and 8; teachers reported about adolescents'
      aggressive behaviors in grades 6, 7, and 8. Path analysis was used to examine
      direct and indirect associations between community violence exposure in grade 6
      and suicide ideation and attempt in grade 8. Depressive symptoms and aggressive
      behavior were examined as part of an indirect path from grade 6 community
      violence exposure to later suicide ideation and attempt. RESULTS: Results
      revealed an indirect association between community violence exposure and later
      suicide ideation for males and females; community violence exposure in grade 6
      was associated with depressive symptoms in grade 7, which in turn, were
      positively associated with suicide ideation in grade 8. For males, community
      violence exposure in grade 6 was associated with increases in aggressive behavior
      in grade 7, which in turn, were associated with suicide attempts in grade 8.

PMID- 18809137
TI  - Adoption of risk-related factors through early adolescence: associations with
      weight status and implications for causal mechanisms.
AB  - PURPOSE: To examine cross-sectional and longitudinal associations between weight
      status and measures of risk and protective factors in youth. METHODS:
      Participants included 3010 students (72.1% white, 27.9% nonwhite), with a
      baseline mean age of 12.7 years from the Teens Eating for Energy and Nutrition at
      School (TEENS) study. Surveys were administered in grades 7 and 8. Cross
      sectional and longitudinal mixed-effects regression analyses were conducted to
      determine the association between body mass index z-score percentiles (BMI) and
      risk and protective factors (including substance use, depression, fighting,
      optimism, and spirituality). RESULTS: Only depression was associated with BMI at
      the beginning of grade 7. However, by the end of grade 8, binge drinking,
      alcohol, tobacco, and other drug (ATOD) use, fighting, and depression were all
      cross-sectionally associated with BMI. Longitudinally, BMI in grade 7 did not
      predict risk and protective factors in grade 8. However, ATOD use, fighting,
      depression, and optimism in grade 7 predicted BMI in grade 8. CONCLUSIONS: This
      study suggests there is a notable co-occurrence of unhealthy factors (including
      weight status, ATOD use, depression) which appears to develop during the critical
      transition period through early adolescence. Specifically, earlier ATOD use,
      depression, increased fighting, and decreased optimism may lead to unhealthy
      increases in weight status, whereas early indicators of increased weight status
      do not appear to predict increases in these factors. This work yields important
      insights into the causal mechanisms underlying adolescent behavior patterning and
      the progression with which these unhealthy risk factor profiles are adopted
      during this critical age.

PMID- 18809138
TI  - Reducing early smokers' risk for future smoking and other problem behavior:
      insights from a five-year longitudinal study.
AB  - PURPOSE: To identify risk and protective factors during early and later
      adolescence that predict future regular smoking and multiple problem behavior
      among at-risk youth, defined as those who tried smoking by grade 7. METHODS: At
      grades 7, 10, and 12, data were collected from 2,000 early smokers drawn from
      California and Oregon. Multivariate regression analyses tested predictors of the
      two grade 12 outcomes in separate models using data from grades 7 and 10. Gender
      interactions and buffering of risk factors by protective factors were assessed.
      RESULTS: For at-risk youth, consistent protective factors against future smoking
      and problem behavior included living in an intact nuclear family (all four
      models) plus getting good grades and parental disapproval of smoking/drug use
      (three of four models). Consistent risk factors included exposure to substance
      using peers (four models) and problems in school (three of four models). Adult
      substance use was a predictor during early, but not later, adolescence; pro
      smoking/drug use beliefs were significant predictors during later adolescence.
      There were few differences across gender and no significant buffers against risk.
      CONCLUSIONS: At-risk youth would likely benefit from peer resistance training,
      parental involvement in prevention efforts, and efforts to improve educational
      performance during both middle school and high school. Changing pro-drug beliefs
      may be more effective among older adolescents.

PMID- 18809139
TI  - Preventing youth problem behaviors and enhancing physical health by promoting
      core competencies.
AB  - OBJECTIVES: The purpose of the present study was to investigate the longitudinal
      relations between specific core competencies, problem behaviors, and physical
      health among adolescents. METHODS: The study used two waves of data collected 1
      year apart from the Add Health data set. The Add Health data set is a nationally
      representative sample of adolescents in grades 7 to 12. A total of 14,010
      respondents were included in this study. There were two outcomes that were
      examined in this study: problem behavior (as observed by seven different
      behaviors), and health (general health and physical problems). RESULTS: We found
      that problem behavior and health outcomes were two distinct behavioral patterns
      that were related to one another. The two outcomes also shared common
      developmental predictors. CONCLUSIONS: Our findings suggest that a focus on core
      competencies is an important target for preventive interventions; among the
      competencies measured low self-control was the strongest single predictor of
      problem behaviors and adverse health outcomes.

PMID- 18809140
TI  - Pediatricians' intention to recommend human papillomavirus (HPV) vaccines to 11-
      to 12-year-old girls postlicensing.
AB  - We surveyed 105 pediatric clinicians following Human papillomavirus (HPV) vaccine
      licensure to identify factors associated with intention to recommend the vaccine
      to 11- to 12-year-old girls. Pediatricians who were early adopters of medical
      technologies had fewer concerns about HPV vaccine safety/efficacy, and who
      anticipated parental vaccine safety/efficacy concerns reported higher intention
      to recommend the vaccine.

PMID- 18809141
TI  - Family influences, acculturation, and the prevalence of tobacco smoking among
      Asian youth in New Zealand: findings from a national survey.
AB  - The associations among family factors, acculturation, and the risk of regular
      smoking among Asian youth were investigated in a nationally representative survey
      in New Zealand. The strong relationships between protective family factors and
      lower risks of smoking were not attenuated in the presence of indicators
      suggestive of acculturation.

PMID- 18809142
TI  - Issues in human papillomavirus vaccination in adolescents.

PMID- 18809143
TI  - HPV Vaccines: today and in the Future.
AB  - Human papillomavirus (HPV) is responsible for 99.7% of cervical cancer cases and
      an estimated 5% of all cancers worldwide. The largest burden from HPV-associated
      cervical cancers is in developing nations where effective cervical cancer
      screening programs are nonexistent. Even in developed nations, diagnosis and
      treatment of cervical precancers continue to be large economic burdens.
      Prophylactic vaccination against HPV is an ideal method for the prevention of
      cervical cancer and other HPV associated diseases. Safe and effective virus-like
      particle-derived prophylactic vaccines are available to most nations. The high
      cost of the current vaccines makes it out of reach for most developing nations.
      Because millions of women are already infected with HPV and have serious disease,
      therapeutic HPV vaccines are being developed to treat these women. This article
      presents the natural history, oncogenesis, and host immune interactions of HPV
      and associated diseases. The article also discusses the safety and efficacy of
      commercially available prophylactic vaccines against HPV, as well as novel
      prophylactic and therapeutic vaccine delivery strategies in early clinical
      development.

PMID- 18809144
TI  - Updated guidelines for papanicolaou tests, colposcopy, and human papillomavirus
      testing in adolescents.
AB  - Worldwide, cervical cancer is a major health concern for women of all ages;
      however the epidemiology and biology of human papillomavirus (HPV) infection
      differs in female adolescents and adults. In the United States, 50% of adolescent
      and young women acquire HPV within 3 years after initiating sexual intercourse,
      resulting in relatively high prevalence rates. Most infections, however, are
      transient and clear within several months. Consequently HPV infections detected
      in adolescents are likely to reflect benign disease, whereas infections detected
      in older women are likely to reflect persistent infections and a higher risk of
      advanced cervical intraepithelial lesions that can lead to invasive cervical
      cancer. This article reviews the most recently published guidelines for the
      prevention of cervical cancer through screening and management of abnormal
      cervical cytologic and histologic findings, which have been updated to reflect
      the differences in HPV infections and cervical abnormalities in female
      adolescents and adults.

PMID- 18809145
TI  - Age-specific prevalence of infection with human papillomavirus in females: a
      global review.
AB  - PURPOSE: Global data on age-specific prevalence of human papillomavirus (HPV)
      infection overall, and for high-risk HPV types 16 and 18, are essential for the
      future implementation of HPV prophylactic vaccines for cervical cancer
      prevention. METHODS: A systematic review of peer-reviewed publications was
      conducted to summarize worldwide data on genital HPV-DNA prevalence in women.
      Studies with clear descriptions of polymerase chain reaction or hybrid capture
      detection assays were included. RESULTS: A total of 346,160 women were included
      in 375 studies. Of 134 studies with age-stratified HPV prevalence data (116 low
      sexual risk populations, 18 high sexual risk populations), over 50% were from
      Europe and the Middle East (38%) and North America (19%), with smaller
      proportions from Asia and Australia (21%), Central and South America (11%), and
      Africa (10%). Across all geographical regions, data on HPV prevalence were
      generally limited to women over 18 years of age. Consistently across studies, HPV
      infection prevalence decreased with increasing age from a peak prevalence in
      younger women (< or =25 years of age). In middle-aged women (35-50 years),
      maximum HPV prevalence differed across geographical regions: Africa
      (approximately 20%), Asia/Australia (approximately 15%), Central and South
      America (approximately 20%), North America (approximately 20%), Southern
      Europe/Middle East (approximately 15%), and Northern Europe (approximately 15%).
      Inconsistent trends in HPV prevalence by age were noted in older women, with a
      decrease or plateau of HPV prevalence in older ages in most studies, whereas
      others showed an increase of HPV prevalence in older ages. Similar trends of HPV
      16 and/or 18 prevalence by age were noted among 12 populations with available
      data. DISCUSSION: Genital HPV infection in women is predominantly acquired in
      adolescence, and peak prevalence in middle-aged women appears to differ across
      geographical regions. Worldwide variations in HPV prevalence across age appear to
      largely reflect differences in sexual behavior across geographical regions.
      Further studies of HPV prevalence in adolescents are needed for all geographic
      regions.

PMID- 18809147
TI  - Potential barriers to HPV vaccine provision among medical practices in an area
      with high rates of cervical cancer.
AB  - PURPOSE: Potential barriers to widespread vaccination of adolescent girls against
      human papillomavirus (HPV) infection are poorly understood. We provide an
      overview of potential barriers to provision of HPV vaccine and empirical data on
      the concerns of medical practices that may inhibit HPV vaccine provision. METHOD:
      We conducted phone interviews with medical practices in rural areas in
      southeastern North Carolina with high rates of cervical cancer to assess 10
      potential concerns about HPV vaccine provision. RESULTS: Concerns most commonly
      reported by medical practices (N = 71) were inadequate reimbursement (68%), high
      cost of the vaccine to patients (66%), and burden of determining insurance
      coverage (66%). Practices that were not providing the vaccine reported more
      concerns about HPV vaccine provision on average than practices providing the
      vaccine (6.0 vs. 4.5 concerns, p < .05). CONCLUSIONS: Medical practices' concerns
      about the HPV vaccine may be barriers to stocking it and, thus, to providing it
      to adolescents. Even providers who stock the vaccine reported concerns. Research
      is needed to address ways to ameliorate these medical practices' concerns and
      also to understand other potential barriers to vaccine coverage.

PMID- 18809146
TI  - Human papillomavirus-related diseases: oropharynx cancers and potential
      implications for adolescent HPV vaccination.
AB  - Molecular and epidemiological data now support an etiologic role for oncogenic
      human papillomavirus (HPV) in oral cancers in women and men. Recent studies have
      demonstrated an increase in the incidence of HPV-associated oral cancers in the
      United States. Moreover, the incidence rates for these cancers are higher in men
      than women. Oral HPV infections acquired through oral sex appear to be the
      principal risk factor for HPV-associated oral cancers. Despite reports in the
      popular press that the prevalence of oral sexual behaviors is increasing in the
      adolescent population, trends in these behaviors over time are largely
      unavailable. However, data indicate that oral-genital contact is frequently
      practiced among adolescents; adolescents do not typically consider this a risky
      behavior. The majority of oral cancers (approximately 90%) caused by HPV are
      identified as HPV 16 positive. Therefore, HPV-associated oral cancers could be
      prevented by a prophylactic vaccine if the vaccine were demonstrated to be
      capable of preventing oral HPV 16 infection. These findings have created new
      potential opportunities for the primary prevention of oral cancers.

PMID- 18809148
TI  - Hemoglobin-based oxygen carriers as blood substitutes.

PMID- 18809149
TI  - Statin, the black box.

PMID- 18809150
TI  - To discharge or not to discharge?

PMID- 18809151
TI  - Feasibility of outpatient coronary angiography with "ad hoc" angioplasty.
AB  - To assess the feasibility and safety of coronary angiography combined, where
      necessary, with ad hoc angioplasty in an outpatient setting; a prospective,
      single-center study. The first 172 patients (154 men, 59 +/- 11 years) considered
      at low risk for complications were enrolled for outpatient-coronary angiography
      with or without angioplasty via a radial approach. The inclusion criteria were
      clinical, not based on angiography. After angiography/angioplasty, creatinine and
      troponin were assayed (outside the hospital) within 24h and patients were
      telephoned and asked about their clinical condition. Angioplasty was performed in
      69 (40%) patients and 130 patients (75.6%) were discharged on the same day. In
      the angioplasty group, a history of coronary dilatation was more common in
      patients discharged on the same day (p = 0.05), whereas bifurcation lesions were
      more frequent in subjects who were kept in hospital (p < 0.0001). No serious
      complications occurred during the study. Of the 42/172 prolonged
      hospitalizations, eight were due to minor procedural complications, five due to
      failure of the radial route and three for indications for bypass surgery; the
      others were kept in for reasons unrelated to a complication (e.g., the
      examination was performed late in the day, a particularly complex procedure,
      etc.). Four (3%) of the 24-hour telephone calls led to a visit, but not hospital
      admission. Overall, performing angiography and "ad hoc" angioplasty in the course
      of a single outpatient visit makes it possible to foreshorten the hospital stay
      and increase patient throughput with a given hospital capacity and, this, without
      increasing clinical risk. Exactly how these patients are selected remains to be
      defined and may certainly be improved compared to this initial experiment. An
      outpatient-coronary angiography and ad hoc angioplasty strategy is a viable
      option with a low risk for patients selected on the basis of simple clinical
      criteria. It combines the advantages of increased convenience for the patient and
      lower costs.

PMID- 18809152
TI  - Is the aortic root dilated in obstructive sleep apnoea syndrome?
AB  - BACKGROUND: Obstructive sleep apnoea syndrome (OSAS) is associated with an
      increased risk of arterial hypertension (AH), coronary artery disease, atrial
      arrhythmias, heart failure, stroke and death. Whether OSAS influences aortic root
      size has not been fully investigated. The aim of our study was to investigate
      aortic root diameter and aortic stiffness in OSAS. METHODS: Using transthoracic
      Doppler echocardiography, we evaluated 76 patients with OSAS (mean age 52.7 +/-
      9.5 years, 70 men [92%]) with no overt cardiovascular disease. The following
      parameters were measured offline: aortic diameter at Valsalva sinuses, aortic
      regurgitation (AR) grade, left ventricular (LV) mass, LV ejection fraction (LVEF,
      Simpson rule), systolic pulmonary artery pressure (sPAP). Aortic stiffness
      (carotid-femoral pulse wave velocity, PWV) was measured non-invasively using
      SphygmoCor technology. RESULTS: Mean duration of OSAS was four years and 84% of
      patients were being treated with continuous positive airway pressure. AH was
      documented in 39 (51%) patients. The mean aortic root diameter was 35.3 +/- 3.8
      mm (26.9-44.6 mm) and the prevalence of aortic root dilatation was 3.9% (3 of 76
      patients). On univariate analysis, age and sex were significant predictors of
      aortic root dilatation whereas arterial hypertension was not. CONCLUSIONS: The
      prevalence of aortic root enlargement was not increased in OSAS. Only age and sex
      and not arterial hypertension, were associated with aortic dilatation.

PMID- 18809153
TI  - Effects of rosuvastatin and atorvastatin on the apolipoprotein B/apolipoprotein A
      1 ratio in patients with an acute coronary syndrome: The CENTAURUS trial design.
AB  - BACKGROUND: The mechanism underlying rapid, statin-induced event reduction in
      patients with an acute coronary syndrome (ACS) remains to be clarified. AIM: The
      primary objective is to compare the efficacy of rosuvastatin 20 mg/day and
      atorvastatin 80 mg/day in reducing the apolipoprotein B/apolipoprotein A-1
      (apoB/apoA-1) ratio at three months, in ACS patients. Secondary objectives
      include a comparison of the effects of early-started rosuvastatin and placebo on
      inflammatory markers. METHODS: This is a randomized, double-blind, parallel-group
      study. Patients with non-ST-segment elevation ACS, symptom onset less than 48 h
      before admission, and for whom a percutaneous coronary intervention is planned,
      are eligible for inclusion and are randomized into three groups (G1, G2 and G3).
      The study comprises two double-blind periods. Period 1 starts at hospital
      admission and lasts until Day 0 (discharge or less or equal to 6 days after
      admission); patients in G1 receive one tablet of rosuvastatin 20 mg/day and
      patients in G2 and G3 receive one matching placebo tablet per day. Period 2
      starts at Day 0 and lasts for three months; patients in G1 continue to receive
      rosuvastatin 20 mg/day, patients in G2 receive rosuvastatin 20 mg/day and
      patients in G3 receive atorvastatin 80 mg/day. Recruitment of 1075 patients will
      ensure an 80 power to detect a 3% difference in percentage change in the
      apoB/apoA-1 ratio and a 20% difference in percentage change in high-sensitivity C
      reactive protein. RESULTS: Inclusion phase is complete; results will be reported
      at a later date. CONCLUSION: This is the first trial investigating the effect of
      statins on apolipoproteins in ACS patients.

PMID- 18809154
TI  - When and how to assess an asymptomatic ventricular pre-excitation syndrome?
AB  - Sudden cardiac death may be the first event in the history of Wolff-Parkinson
      White syndrome: this is a very rare event although as ablation of the accessory
      pathway avoids this risk a potentially malignant form of the disease needs to be
      detected. Electrophysiological studies are the most reliable method. These may be
      performed by a trans-oesophageal or endocavity approach from the age of six to
      seven years onwards. Whilst it is rare to detect a potentially malignant form the
      results of these studies more often enable the person to play sports or continue
      their job without offering radio-frequency ablation. The former however is
      indicated when tachycardia is induced in children over 12 years old and in
      adults.

PMID- 18809155
TI  - Retrograde catheterization of the right heart in patients with occluded femoral
      veins.
AB  - BACKGROUND: Occlusion of the femoral veins is a frequent complication of cardiac
      catheterization in small children. If the venous femoral approach is not
      available, a jugular approach is generally used for catheterization of the right
      heart. AIMS: To describe and evaluate an alternative retrograde approach for
      catheterization of the right heart in small children with a ventricular septal
      defect or single ventricle. METHODS: Between January 2004 and January 2007 we
      attempted retrograde catheterization of the right heart via the femoral artery
      using a 4 French sheath in eight children with occluded femoral veins. The
      procedure was planned under awake sedation. RESULTS: Median age was five months
      (range 4-60) and median weight was 5 kg (range 4-10). Diagnoses were as follows:
      single ventricle (n = 6); pulmonary atresia and ventricular septal defect (n =
      1); complex transposition of the great arteries (n = 1). The procedure was
      successful in six patients, enabling measurement of pulmonary arterial pressure
      and pulmonary angiography. The procedure was abandoned in two patients because of
      ventricular arrhythmias. One patient had concomitant dilatation of aortic
      recoarctation and one had embolization of aortopulmonary collaterals. With the
      exception of transient ventricular arrhythmias, no acute or late complications
      occurred. In particular, transient or permanent atrioventricular block,
      occurrence of new aortic insufficiency, and acute or late thrombosis of the
      femoral artery were not observed. CONCLUSION: Retrograde catheterization of the
      right heart in small children is feasible and relatively safe. This technique can
      be performed without general anaesthesia and avoids a jugular approach.

PMID- 18809156
TI  - European National Society Cardiovascular Journals background, rationale and
      mission statement of the "Editors' Club" (Task Force of the European Society of
      Cardiology).

PMID- 18809158
TI  - Dobutamine stress induced severe prolonged left ventricular dysfunction.

PMID- 18809157
TI  - Imaging techniques for diagnosing a giant coronary artery fistula.

PMID- 18809159
TI  - Numbers.

PMID- 18809160
TI  - Counting forward.

PMID- 18809161
TI  - Can interview prior to laparoscopic simulator training predict a trainee's
      skills?
AB  - BACKGROUND: Our institute started laparoscopic simulator training for medical
      students in 2006. During the training, we observed considerable interindividual
      differences in laparoscopic skills among those students. This study aimed to
      investigate the predictive factors that affect laparoscopic skill by assessing
      the students' training results data. METHODS: Forty-three, fifth-year medical
      students were asked several questions and were divided into 2 groups depending on
      their answers. The participants performed an object-positioning module on a
      ProMIS simulator (Haptica, Inc., Dublin, Ireland). Execution time, instrument
      path length, and economy of movement for each trial were recorded on ProMIS.
      Comparisons of mean performance measures between the 2 groups were made using a
      Mann-Whitney U test. RESULTS: Interest about laparoscopic surgery and
      accomplishment in playing piano did not affect the skillfulness significantly.
      The students who had an interest in television (TV) games completed the task in
      less time (p = 0.046) and had a shorter left instrument path length (p = 0.012).
      The students who thought themselves manually dexterous completed the task in less
      time (p = 0.008). The students who were confident about driving completed the
      task in less time (p = 0.0247). DISCUSSION: In our interview, the factors that
      had a relationship to laparoscopic skills were favorableness to TV games, manual
      dexterity, and confidence about driving. These results were expected because TV
      games and driving a car require the same abilities as laparoscopic surgery.
      Psychomotor, perceptual, or visuospatial ability are essential for good
      performance. In conclusion, our study suggests that the interview can be an
      effective measure to examine the aptitude of medical students without the use of
      a simulator.

PMID- 18809162
TI  - Evaluation of selective treatment of penetrating abdominal trauma.
AB  - OBJECTIVE: In penetrating abdominal trauma, diagnostic imaging and the
      application of selective clinical management may avoid negative celiotomy and
      improve outcome. DESIGN: We prospectively observed patients with penetrating
      abdominal trauma over 15 months and recorded demographics, presentation, imaging,
      surgical procedure, and outcome. Patients who underwent immediate laparotomy were
      compared with patients who were observed and/or had a computed tomography (CT)
      scan. Outcomes of negative versus positive and immediate versus delayed celiotomy
      were compared. Chi-square and Student t tests were used. A p value of less than
      0.05 was considered significant. SETTING: A level 1 trauma center. PARTICIPANTS:
      Adult patients who presented with penetrating abdominal injury. RESULTS: In all,
      100 consecutive patients (mean age, 32 years) were included (male:female, 91:9;
      gunshot wound:stab wound, 65:35). Overall, 60 immediate and 10 delayed
      laparotomies were performed; 30 patients did not undergo surgery. Predictors of
      immediate celiotomy were hypotension (p = 0.03), anteriorly located entrance
      wounds (p = 0.0005), and transaxial wounds (p = 0.03). Overall morbidity and
      mortality was 32% and 2%, respectively. The negative celiotomy rate was 25%.
      Patients with a positive celiotomy had higher morbidity (p = 0.006) and longer
      hospital length of stay (p = 0.003) compared with negative celiotomy. A CT scan
      was employed in 32% of patients, with 100% sensitivity and 94% specificity.
      Delayed celiotomy (10%) did not adversely impact morbidity (p = 0.70) and was
      100% therapeutic, with no deaths. CONCLUSION: Nonselective immediate celiotomy
      for penetrating abdominal trauma results in a high rate of unnecessary surgery.
      Hemodynamically stable patients can safely be observed and/or have contrast CT
      scans and undergo delayed celiotomy, if indicated. This selective treatment had
      no adverse effect on patient outcomes and can potentially improve overall
      outcome.

PMID- 18809163
TI  - Impact of laparoscopic cholecystectomy on resident training: fifteen years later.
AB  - Laparoscopic cholecystectomy was first introduced to our surgical community in
      1989. In 1993, McKellar reviewed the impact of laparoscopic cholecystectomy on 1
      specific surgical training program. Fifteen years later, the authors reexamined
      the implications of laparoscopic surgery on resident competency with both open
      and laparoscopic biliary procedures. The data reveal a statistically significant
      increase in the percentage of laparoscopic cholecystectomies performed when
      compared with total cholecystectomies (open plus laparoscopic), as well as a
      trend toward decreasing numbers of total common bile duct explorations performed.
      A review of the literature that pertains to changes in resident training as
      related to laparoscopic procedures is included.

PMID- 18809164
TI  - Intraoperative breast problem--focused sonography a valuable tool in the training
      of surgical residents.
AB  - INTRODUCTION: In surgical residency education, "hands-on" learning is important
      in the operating room. Mastering the interpretation of preoperative data is a
      must for intraoperative decisions. Because preoperative evaluations of breast
      masses by ultrasound are performed and interpreted in the Department of
      Radiology, our study aimed to assess and improve surgical residents' ability to
      perform ultrasound and to interpret their results before performing breast mass
      biopsies. METHODS: Between January 2000 and May 2007, 128 female patients found
      to have palpable breast masses were scheduled for biopsy. An on-table ultrasound
      was performed by a surgical resident under the supervision of an attending
      surgeon. The resident was unaware of the result reported by the Department of
      Radiology. The parameters used to evaluate on-table ultrasound were the
      echogenicity, diameter (transverse vs vertical), and margins (regular vs
      irregular) of patients' lesions. Based on these criteria, residents classified
      lesions as benign, malignant, or indeterminate. The results were compared with
      the preoperative ultrasound evaluations provided by the Department of Radiology
      and pathology reports. RESULTS: Eliminating the 10 indeterminate lesions on
      ultrasound, the residents found that 87 lesions were benign and 31 lesions were
      malignant. The residents' assessment of the breast lumps had a sensitivity of
      90.32% and a specificity of 96.55%, with a positive predictive value of 90.32%
      and a negative predictive value of 96.55%. CONCLUSIONS: The residents' overall
      accuracy of 94.91% approximates that of the radiologists in differentiating
      between benign and malignant lesions. The study allowed us to assess the
      knowledge and skills of residents who responded as required by Accreditation
      Council for Graduate Medical Education core competencies.

PMID- 18809165
TI  - What do physician extenders in a general surgery residency really do?
AB  - OBJECTIVE: The 80-hour workweek has forced surgical training programs to employ
      physician extenders to reduce work hours and improve the educational environment.
      The purpose of our study was to document objectively the specific workload
      provided by physician extenders and to evaluate any objective or subjective
      benefit provided to the residency program. METHOD: Over 4 consecutive months, all
      orders written by 2 physician extenders associated exclusively with the general
      surgery residency program at our institution were reviewed. They were categorized
      as daytime or evening orders and were subdivided into admission, routine
      preoperative and postoperative, acute care, daily laboratories, pain medications,
      Pro re nata (PRN), wound care, and discharge orders. Acute care issues and PRN
      orders were individually examined and subdivided. The appropriateness, total
      volume, and the orders for each category were totaled and reviewed. RESULTS:
      Overall, 3101 total orders (1128 daytime and 1973 nighttime) were reviewed in a 4
      month time period. On average, physician extenders at night wrote 35 orders per
      shift, compared with only 18.8 orders during the day. During the night, admission
      orders totaled 547 (27.7%), preoperative orders 442 (22%), acute care issues 324
      (16.4%), PRN orders 239 (12%), and pain medication and PRN sleeping pills 156
      (8%). During the day, routine postoperative orders totaled 305 (27%), daily
      laboratories 184 (16%), and discharge orders 253 (22%). CONCLUSION: Physician
      extenders wrote appropriate orders and reduced resident workload. Educational
      opportunities increased because fewer residents left conference for acute patient
      care issues, and 1 fewer resident was absent during the day secondary to 1 less
      resident being sent home postcall. Performance on the American Board of Surgery
      In-Training Examination (ABSITE) increased dramatically for a focused group of
      residents. As the expense of each extender is approximately $90,000,
      justification to administration is dependent on the institutional support and
      efficiency of the residency program. A clear simple outcome is that by improving
      standing orders and clinical pathways, and by using an electronic medical record
      system, noneducational work hours can be reduced significantly.

PMID- 18809166
TI  - Will a 1-page informational handout decrease patients' most common fears of
      anesthesia and surgery?
AB  - OBJECTIVE: The objective of this study was to determine whether an informational
      handout alone could measurably reduce some of the most common fears patients have
      about anesthesia and surgery. DESIGN: An anonymous, volunteer survey package
      consisting of demographic information, a 1-page informational handout discussing
      common fears that patients have, and 2 identical surveys that assessed the
      patients' level of fear before and after reading the handout. SETTING: Wilford
      Hall Medical Center, Lackland Air Force Base, San Antonio, Texas. PARTICIPANTS: A
      total of 387 random volunteer patients awaiting their clinic visit with a
      provider in the Anesthesiology Pre-Operation Clinic of Wilford Hall Medical
      Center properly filled out the survey package. METHODS: Patients were asked to
      rate their fears with respect to (1) the qualification of their anesthesia
      providers, and the potential for (2) death or serious illness, (3) awareness, (4)
      postoperative pain, (5) access to pain medications postoperatively, and (6)
      postoperative nausea and vomiting. The patients rated their fears for each of the
      6 categories using a Likert scale as either none, mild, moderate, or severe,
      which corresponded to scores of 0, 1, 2, or 3, respectively, for a maximum fear
      score of 18. The patients were then asked to read a 1-page objective
      informational handout that addressed each of these potential fears. After reading
      the informational handout, the patients then repeated the fear survey. RESULTS:
      Three hundred eighty-seven patients properly completed the survey packages. There
      were 160 (41.3%) patients who demonstrated a reduction in fear scores, with a
      49.6% (p < 0.001) reduction between the mean initial fear score of 6.81 (CI 6.11
      to 7.52) and mean final scores of 3.43 (CI 2.84 to 4.02). The most commonly
      reported fear was death (n = 196, 50.6%), and those patients with no prior
      surgeries (n = 63, 17.3%) had the highest initial mean fear score of 5.13 (CI
      3.79 to 6.37) and the largest reduction in their fear score with 36.1% (p <
      0.001). Those patients between the ages of 26 years old and 39 years old had the
      high initial mean fear score of 5.39 (CI 4.37 to 6.30), whereas patients under
      the age of 25 years old had the largest reduction in their fear score with 37.6%
      (p < 0.001). Subset analysis of patients whose mean fear scores were reduced
      after reading the handout were found to have statistically significant higher
      initial mean fear scores and a larger overall reduction in fear scores. Neither
      initial fear scores nor a reduction in fears scores were found to correlate with
      the type of surgery a patient was planning to have. CONCLUSION: With just over
      40% of patients demonstrating a statistically significant reduction in their fear
      levels, consideration should given to making an informational handout available
      on a routine basis to patients in preoperative anesthesia and surgical clinics.
      Additionally, it seems that younger patients (under the age of 40 years old) and
      those with no prior surgeries are the most likely to benefit from such a handout.

PMID- 18809167
TI  - Recurrence of primary breast lymphoma in contralateral breast: case report and
      review of the literature.
AB  - Lymphoma presenting as a breast mass is rare, although well documented. Although
      recurrence rates can reach approximately 50%, recurrence in the contralateral
      breast is rare. We report a case of recurrent primary breast lymphoma (PBL),
      which was discovered on screening mammography after a 5-year disease-free
      interval from initial diagnosis.

PMID- 18809168
TI  - Type II gall bladder perforation with abdominal wall abscess in a cirrhotic
      patient: case report and review of the literature.
AB  - Gallbladder perforation is a rare condition even in patients affected by acute
      cholecystitis. Most patients who present with gallbladder perforations are
      diagnosed preoperatively by radiologic imaging. Morbidity and mortality for this
      condition has improved significantly over the last few decades. We encountered a
      cirrhotic patient who was affected by primary sclerosing cholangitis and who
      developed a type II gallbladder perforation before undergoing a cadaveric liver
      transplantation. In this article, we report her clinical course and our review of
      the current literature on this rare condition.

PMID- 18809169
TI  - Staring back down the barrel: the evolution of the treatment of thoracic gunshot
      wounds from the discovery of gunpowder to World War II.

PMID- 18809170
TI  - International volunteerism during general surgical residency: a resident's
      experience.
AB  - OBJECTIVE: The purpose of this article is to discuss a surgical resident's
      experience in Kenya as a component of a custom-designed dedicated year. The
      academic value, clinical experience, and lessons learned will be described.
      Hopefully, these insights will be useful to those planning to take a similar
      course or for those seeking to offer such an experience at their training
      programs. SETTING: Bomet, Kenya. RESULTS: Operative experience for a 6-month
      period is given in Table 1. Two papers were presented at the 58th East African
      College of Surgeons conference. Retrospective review of the local experience in
      treatment of esophageal and breast cancers were reported for a 14-year period.
      CONCLUSIONS: Concerning the goals and value of surgical volunteerism during
      residency, the greatest benefits are derived personally by the volunteer. If
      careful preparation is made, then it is possible to obtain meaningful research
      data even from a small village in East Africa. The inherent risks of third-world
      travel can be optimized but not erased.

PMID- 18809171
TI  - Global health opportunities in surgery: a guide for medical students and faculty.
AB  - INTRODUCTION: A four-week surgical rotation at the Clinica Universitaria Teleton
      in Chia, Colombia, was arranged for a U.S. student at the completion of the first
      year of medical school. The rotation resulted in a supervised intense early
      clinical exposure to surgery resulting in advancement in five of the six clinical
      competencies. CONCLUSION: International medical experiences can provide great
      benefit to U. S. medical students.

PMID- 18809172
TI  - "The whale".

PMID- 18809173
TI  - Microgels: From responsive polymer colloids to biomaterials.
AB  - Microgels are network polymer colloid particles that can swell in a good solvent
      or as a result of electrostatic repulsion between charged groups produced by pH
      triggered neutralisation. They have attracted considerable interest as both model
      colloids and for their potential applications. This discussion reviews the
      properties of microgel particles and the current understanding of their
      structure. The review concentrates on the period after an earlier microgel review
      by Saunders and Vincent [Adv. Coll. Interf. Sci., 1999, 80, 1]. A key challenge
      for microgel research has involved elucidation of the internal particle
      structure. Most microgels prepared by emulsion or precipitation polymerisation
      have a core-shell structure. The segment density is usually highest in the core.
      Here, we discuss relationships between microgel structure and dispersion
      stability. The reasons for the exceptional stability of microgel dispersions are
      considered. There are a number of favourable structural features that make
      microgels candidates for biomaterial applications and these are discussed. The
      main potential biomaterial applications that have been investigated for microgels
      to date are drug delivery and regenerative medicine. Poly(NIPAM) (N
      isopropylacrylamide) microgels have been extensively studied in the context of
      drug delivery. Regenerative medicine research for microgels is an emerging area.
      Recent work involving the use of gelled microgel dispersions to support
      biomechanically meaningful loads is considered. We conclude with a discussion of
      promising directions for microgel research as biomaterials.

PMID- 18809174
TI  - Synthesis of beta-D-arabinofuranosides: stereochemical differentiation between D-
      and L-enantiomers.
AB  - The glycosylation of 3,5-O-di-tert-butylsilylene-protected d
      thioarabinofuranosides with a range of glycosyl acceptors using NIS/AgOTf as
      promoters proceeded in a stereoselective manner to give the corresponding beta-D
      arabinofuranosides in high yields.

PMID- 18809175
TI  - Vascular oxidative stress increases dendritic cell adhesion and transmigration
      induced by homocysteine.
AB  - Atherosclerosis is a long-term chronic inflammatory and immunological disease.
      Endothelial dysfunction and the dendritic cell (DC) immune response are pivotal
      early events in atherogenesis. This study investigated the effects and possible
      mechanisms of action of homocysteine (Hcy) on DC adhesion to and transmigration
      between endothelial cells (ECs), and indicated a novel immunoregulatory mechanism
      by which Hcy induces atherogenesis. When ECs were stimulated with increasing
      concentrations of Hcy, immunofluorescence showed that endothelial reactive oxygen
      species (ROS) generation strikingly increased, while nitrite assay showed that
      nitric oxide (NO) release markedly decreased. Furthermore, DC adhesion and
      transmigration were significantly increased when ECs were activated by Hcy.
      However, pretreatment of ECs with antioxidant before Hcy markedly attenuated the
      induction of DC adhesion and transmigration, dependent on the intracellular ROS
      decrease and endothelial NO increase. In conclusion, DC adhesion and
      transmigration are significantly increased by vascular oxidative stress under
      conditions of elevated Hcy levels. These findings provide insight into the
      inflammatory processes and immune responses occurring in atherosclerosis induced
      by Hcy.

PMID- 18809176
TI  - The relations between children's communicative perspective-taking and executive
      functioning.
AB  - Two experiments investigated children's communicative perspective-taking ability.
      In Experiment 1, 4- to 5-year-old children were tested on two referential
      communication tasks, as well as on measures of inhibitory control, working
      memory, and cognitive flexibility. Results document children's emergent use of
      the perspective of their speaking partner to guide their communicative behaviors
      in both a production and comprehension task. In Experiment 2, 3- to 4-year-old
      children used a speaker's perspective to guide their interpretation of
      instructions. In both experiments, egocentric interpretations of speaker requests
      were negatively correlated with children's inhibitory control skills. Results of
      these studies demonstrate that young children can differentiate between
      information that is accessible to the speaker versus privileged knowledge, and
      use this information to guide their communicative behaviors. Furthermore, the
      results suggest that children's inhibitory control skills allow them to inhibit
      their own perspective, enabling them to make use of their communicative partner's
      perspective.

PMID- 18809177
TI  - Low levels of IgM antibodies against phosphorylcholine-A potential risk marker
      for ischemic stroke in men.
AB  - BACKGROUND: Natural antibodies specific for phosphorylcholine (anti-PC) have been
      implicated as protective factors in atherosclerosis. We herein determined the
      relationship between IgM anti-PC and incidence of cardiovascular disease (CVD).
      METHODS: We studied 349 incident cases (200 men) of first events of CVD (coronary
      heart disease (CHD; n=203 or ischemic stroke; n=146) and 693 age- and sex-matched
      controls identified through 12 years of follow-up (1991-2003) of subjects from
      the cardiovascular cohort within the Malmo Diet and Cancer Study. Relative risks
      (RR) of CVD with 95% confidence intervals (CI) of incident CVD with adjustments
      for age, smoking, total cholesterol and blood pressure were determined. Anti-PC
      levels were measured using ELISA (Athera CVDefine). RESULTS: As determined using
      Athera CVDefine, significant associations were attained with values of anti-PC
      below 17U/ml (corresponding to the lowest 9th percentile), which remained after
      taking confounders into account (RR: 1.79, 95% CI: 1.09-2.94, p=0.021). If men
      were studied separately, significance was evident at values below 17U/ml (RR:
      2.01, 95% CI: 1.11-3.67, p=0.022), which was not the case among women.
      Furthermore, values below 17U/ml were also associated with ischemic stroke
      (RR=3.67, 95% CI: 1.34-10.1, p=0.01), but not with CHD. CONCLUSION: Low IgM anti
      PC could be a novel risk marker for development of ischemic stroke in men.
      Further studies are needed to establish gender and subgroup differences.

PMID- 18809178
TI  - Dynamic simulation of viscoelastic soft tissues in harmonic motion imaging
      application.
AB  - A finite element model was built to simulate the dynamic behavior of soft tissues
      subjected to sinusoidal excitation during harmonic motion imaging. In this study,
      soft tissues and tissue-like phantoms were modeled as isotropic, viscoelastic,
      and nearly incompressible media. A 3D incompressible mixed u-p element of eight
      nodes, S1P0, was developed to accurately calculate the stiffness matrix for soft
      tissues. The finite element equations of motion were solved using the Newmark
      method. The Voigt description for tissue viscosity was applied to estimate the
      relative viscous coefficient from the phase shift between the response and
      excitation in a harmonic case. After validating our model via ANSYS simulation
      and experiments, a MATLAB finite element program was then employed to explore the
      effect of excitation location, viscosity, and multiple frequencies on the dynamic
      displacement at the frequency of interest.

PMID- 18809179
TI  - Primary rotational stability of cylindrical and conical revision hip stems as a
      function of femoral bone defects: an in vitro comparison.
AB  - Bone stock losses in cementless femoral stem revisions compromise a stable
      fixation. The surgeon has to rely on his wealth of experience in deciding which
      stem shape to use. The aim of our study was to compare the primary rotational
      stability of cylindrical and conical revision hip stems subjected to femoral
      defects. Four current prostheses (two cylindrical, two conical) were implanted
      into four synthetic femora. Micro-motion was measured under torque application
      and femoral neck osteotomy and segmental AAOS Type I and III defects were
      simulated. The relative movements of all prostheses were significantly influenced
      by the extent of bone loss (p<0.01). Major differences were seen in fixation
      behavior (p<0.01). The main fixation area of conical stems is within the distal
      femoral isthmus, whereas cylindrical implants are dependent on proximal bone
      stock. In our study, cylindrical stems are advantageous for minor defects because
      they provide a proximal fixation. In cases of extensive substance loss, the
      conical implants showed lesser relative movements. These findings should be taken
      into account for clinical decisions.

PMID- 18809180
TI  - Evaluation of solid-phase microextraction methods for determination of trace
      concentration aldehydes in aqueous solution.
AB  - A method for trace analysis of a wide range of aldehydes (saturated/unsaturated
      aliphatic, aromatic aldehydes, including hydroxylated species, and dialdehydes)
      in an aqueous solution was optimized. An evaluation of three solid-phase
      microextraction (SPME) techniques (headspace, liquid-phase, and on-fiber
      derivatization) with o-(2,3,4,5,6-pentafluorobenzyl)hydroxylamine hydrochloride
      (PFBHA) aldehyde derivatization was performed focusing on the optimization of the
      main extraction parameters (temperature and time). The optimized method employed
      the liquid-phase SPME (D-L-SPME) of derivatized aldehydes at 80 degrees C for 30
      min. Limits of detection (LODs) using this optimal method were in the range of
      0.1-4.4 microg/L for the majority of aliphatic (saturated, unsaturated), aromatic
      aldehydes and dialdehydes. Formaldehyde LODs and those of some hydroxylated
      aromatic aldehydes were between 32 and 55 microg/L. Headspace SPME using an on
      fiber derivatization generally showed a lower sensitivity and several compounds
      were not detected. Another technique, the optimized headspace SPME of aldehydes
      derivatized in aqueous solution, was not as sensitive as D-L-SPME for
      hydroxylated aromatic aldehydes. The developed method was used to analyze aqueous
      particulate matter extracts; this method achieved higher sensitivities than those
      obtained with US Environmental Protection Agency (EPA) Method 556.

PMID- 18809181
TI  - Electron beam triggered, free radical polymerization-derived monolithic capillary
      columns for high-performance liquid chromatography.
AB  - Monolithic capillary columns were prepared via electron beam triggered free
      radical polymerization within the confines of 0.2 and 0.1mm I.D. capillary
      columns using ethyl methacrylate and trimethylolpropane triacrylate as monomers
      as well as 2-propanol, 1-dodecanol and toluene as porogenic system. The influence
      of column diameter on reproducibility and separation performance was
      investigated. For evaluation, a protein standard consisting of five proteins in
      the range of 5800-66,000 g mol(-1) was used. Reproducibility was checked by
      determining the relative standard deviations in retention times, peak widths at
      half height, asymmetry and resolution. Excellent run-to-run reproducibility was
      found for both 0.2 and 0.1mm I.D. columns; batch-to-batch reproducibility was
      good for both column types. In order to enhance the non-polar character of the
      monolithic columns, lauryl methacrylate-based capillary columns were prepared.
      These were successfully used for the separation of proteins and a cytochrome c
      digest.

PMID- 18809182
TI  - Concept-procedure interactions in children's addition and subtraction.
AB  - A 3-week problem-solving practice phase was used to investigate concept-procedure
      interactions in children's addition and subtraction. A total of 72 7- and 8-year
      olds completed a pretest and posttest in which their accuracy and procedures on
      randomly ordered problems were recorded along with their reports of using concept
      based relations in problem solving and their conceptual explanations. The results
      revealed that conceptual sequencing of practice problems enhances children's
      ability to extend their procedural learning to new unpracticed problems. They
      also showed that well-structured procedural practice leads to improvement in
      children's ability to verbalize key concepts. Moreover, children's conceptual
      advances were predicted by their initial procedural skills. These results support
      an iterative account of the development of basic concepts and key skills in
      children's addition and subtraction.

PMID- 18809183
TI  - Demyelinating polyneuropathy with focally folded myelin sheaths in a family of
      Miniature Schnauzer dogs.
AB  - A spontaneous demyelinating polyneuropathy in two young Miniature Schnauzer dogs
      was characterized clinically, electrophysiologically and histopathologically.
      Both dogs were related and a third dog, belonging to the same family, had similar
      clinical signs. On presentation, clinical signs were restricted to respiratory
      dysfunction. Electrophysiological tests showed a dramatic decrease in both motor
      and sensory nerve conduction velocities. Microscopic examination of peripheral
      nerve biopsies (light and electron microscopy, teased nerve fibers), showed that
      this neuropathy was characterized by segmental demyelination and focally folded
      myelin sheaths. Various clinical syndromes associated with tomacula or focal
      thickening of the myelin sheath of the peripheral nerves have been described in
      humans and shown to be caused by gene mutations affecting the myelin proteins,
      such as the hereditary neuropathy with liability to pressure palsies or the
      demyelinating forms of Charcot-Marie-Tooth disease. In animals, a tomaculous
      neuropathy has been reported in cattle and chickens but not in carnivores. Here
      we report a demyelinating peripheral neuropathy with tomacula in two Miniature
      Schnauzer dogs.

PMID- 18809184
TI  - Spatial assessment of fishing effort around European marine reserves:
      implications for successful fisheries management.
AB  - We examined the spatial dynamic of artisanal fishing fleets around five European
      marine protected areas (MPAs) to derive general implications for the evaluation
      of MPAs as fisheries management tools. The coastal MPAs studied were located off
      France, Malta and Spain and presented a variety of spatial designs and processes
      of establishment. We developed a standardized methodology to define factors
      influencing effort allocation and to produce fishing effort maps by merging GIS
      with geostatistical modelling techniques. Results revealed that in most cases the
      factors "distance to the no-take", "water depth", and "distance to the port" had
      a significant influence on effort allocation by the fishing fleets. Overall, we
      found local concentration of fishing effort around the MPA borders. Thus,
      neglecting the pattern of fishing effort distribution in evaluating MPA benefits,
      such as spillover of biomass, could hamper sound interpretation of MPAs as
      fisheries management tools.

PMID- 18809185
TI  - [Transition from childhood to adulthood and lumbosacral dysraphism].
AB  - The diagnosis of lumbosacral dysraphism is now made during the first year of
      life. Although problems due to filum lipomas are solved when the patient becomes
      an adult, the lipomas of the lumbar spinal cord can induce late complications. It
      is therefore necessary to organize a neurological, urological, and obstetrical
      follow-up to: screen for late retethering and/or deterioration ; preserve kidney
      function and monitor the consequences of the different procedures performed
      during childhood ; support pregnancies (delivery, prenatal screening for
      Currarino syndromes).

PMID- 18809186
TI  - [Transition from childhood to adulthood and management of spasticity].
AB  - The authors report specific concerns on the transition to adulthood in cerebral
      palsy patients, with particular attention devoted to spasticity treatment follow
      up.

PMID- 18809187
TI  - Glycocomposition of the apocrine interdigital gland secretions in the fallow deer
      (Dama dama).
AB  - The secretions of the tubular interdigital glands were investigated by
      conventional (Periodic-Acid Schiff, Alcian-Blue at different pH, Low Iron Diamine
      and High Iron Diamine) and lectin (Con-A, UEA-I, LTA, WGA, GSA-II, GSA-IB4, SBA,
      PNA, ECA, DBA, MAL-II and SNA) histochemical methods in adult males and females
      of different age of fallow deer during the breeding season. Sialidase digestion
      and deacetylation pre-treatment were also employed in conjunction with lectin
      histochemistry. The glandular epithelium consisted of a single layer of low
      columnar cells with typical apical protrusions. No substantial differences of the
      above histochemical staining in relation to sex and age were observed.
      Conventional histochemical staining revealed that the interdigital glands
      secreted neutral glycoproteins whereas acidic glycocomponents did not seem to be
      present. Lectin histochemical technique allowed us to disclose a great
      heterogeneity of glycoproteins with N- and O-linked oligosaccharides containing
      alpha-d-Man/alpha-d-Glc, GlcNAc, alpha-Fuc, terminal beta-d-Gal-(1-3)-d-GalNAc, 
      d-Gal-(1-4)-d-GlcNAc, alpha-Gal and beta-GalNAc residues. beta-GalNAc and
      disaccharide beta-d-Gal-(1-3)-d-GalNAc were also found as subterminal to sialyl
      moieties. The lack of sexual and age-related differences in the glucidic content
      of the glandular secretions seems to indicate that the glycoderivatives may play
      only an accessory role in the production of odoriferous signals in fallow deer.

PMID- 18809188
TI  - [Autoimmune limbic encephalitis with anti-NMDA receptor antibodies and ovarian
      teratoma: a treatable form of paraneoplastic limbic encephalitis].
AB  - INTRODUCTION: The first French-language case of limbic encephalitis due to anti-N
      methyl-D-aspartate receptor to glutamate (NMDA-R) antibodies associated with an
      ovarian teratoma is reported. CLINICAL CASE: A 35-year-old woman presented with a
      subacute severe anterograde memory deficit, psychiatric disturbances and
      generalized seizures associated with an ovarian teratoma. No abnormality was
      noticed on the two successive MRI. The cerebrospinal fluid showed mild
      lymphocytosis and elevation of protein concentration. The search for classical
      onconeuronal antibodies in the serum was negative. Total body computed
      tomographic scan disclosed a five centimeter long ovarian cyst. Pathology found
      an ovarian teratoma containing a small immature neuroepithelial component.
      Complete tumor resection associated with high doses of intravenous
      methylprednisolone and intravenous polyvalent immunoglobulins allowed her
      clinical state to improve as soon as three days after surgery. Full recovery was
      noted four months later. Serum anti-NMDA-R antibodies were positive. CONCLUSION:
      Owing to the recent description of the association between anti-NMDA-R and limbic
      encephalitis and the frequent good prognosis reported in the available series and
      case reports, it is important to search for this association in the not so rare
      cases of limbic encephalitis when no other cause is disclosed.

PMID- 18809189
TI  - [Sciatica due to unusual causes: Tarlov cysts and nerve roots anomalies].
AB  - Tarlov cysts and nerve roots anomalies usually involve lumbosacral roots and are
      often asymptomatic. MRI has enabled recognition of many conditions that used to
      be missed by CT or myelography investigations performed for back and leg pain.
      However, even without additional compressive impingement (disc hernia,
      spondylolisthesis or lumbar canal stenosis) these anomalies can be responsible
      for sciatica, motor deficit and bladder sphincter dysfunction. Tarlov cysts are
      perinervous dilatations of the dorsal root ganglion. CT and especially MRI can
      reveal these cysts and their precise relations with the neighboring structures.
      Delayed filling of the cysts can be visualized on the myelogram. MRI is more
      sensitive than CT myelography for a positive diagnosis of nerve root anomalies, a
      differential diagnosis with disc hernia and classification of these anomalies.
      Surgical treatment is indicated for symptomatic Tarlov cysts and nerve root
      anomalies resistant to conservative treatment. Better outcome is observed in
      patients with an additional compressive impingement component. We report two
      cases of sciatica: one caused by Tarlov cysts diagnosed by MRI and the other by
      nerve root anomalies diagnosed by CT myelography. In both cases, conservative
      treatment was undertaken. The clinical, radiological and therapeutic aspects of
      these disorders are discussed.

PMID- 18809190
TI  - Strongyloides stercoralis in the urine.

PMID- 18809191
TI  - A clinical guide for early detection of dengue fever and timing of investigations
      to detect patients likely to develop complications.
AB  - We aimed to identify clinical features that would be useful for case detection
      and the appropriate timing of investigations and hospital admissions in patients
      with short-duration fever, suspected to be dengue fever (DF). Of 928 adult
      patients with short-duration fever admitted to Colombo North Teaching Hospital,
      Sri Lanka during February-June 2004, one in four were randomly selected for
      assessment of the severity of six clinical features: headache, body aches,
      vomiting, retro-orbital pain, generalised weakness (scale 0-9) and skin erythema
      (grade 1-5). There were 148 DF patients (95 males, mean age+/-SD: 28+/-12 years)
      and 54 non-DF patients as controls (44 males, mean age+/-SD: 25+/-11 years). All
      symptoms assessed (cut-off >or=5) and skin erythema (>or=grade 2) had a good
      positive predictive value for DF. However, erythema had the best negative
      predictive value, helping to differentiate DF from other short-duration fevers.
      More than 95% of patients with dengue had a platelet count above 50000/microl
      until the third day of illness. The platelet counts were significantly reduced
      when erythema, fever, vomiting and generalised weakness were persistent. In
      conclusion, erythema elicited by hand impression may help in the prediction of
      DF, and follow-up blood counts are indicated when symptoms persist.

PMID- 18809192
TI  - Mansonella perstans filariasis in Uganda: patterns of microfilaraemia and
      clinical manifestations in two endemic communities.
AB  - Surveys for Mansonella perstans infection and potentially related clinical
      manifestations were undertaken in two endemic communities in Mukono and Luwero
      districts of Uganda where no other human filarial infections are transmitted. A
      sensitive and accurate counting chamber method was used for quantifying
      microfilaraemia in 100microl of finger-prick blood. Among 575 and 991 examined
      individuals aged >or=1 year in the two communities, the overall microfilariae
      (mf) prevalence was significantly higher in Mukono (76.5%) than in Luwero
      (57.7%). As early as age 1-4 years, 40.6% and 20.5% of the children were mf
      positive. Prevalences increased rapidly with increasing age to reach 89.2% and
      81.4% in the 15-19 years age group and then remained high in subsequent age
      groups. The geometric mean mf intensity among mf-positive individuals was
      slightly higher in the Mukono community (32.4mf/100microl) than in the Luwero
      community (29.9mf/100microl), and this parameter increased with age in both
      communities. No obvious associations were observed between various clinical
      parameters and M. perstans microfilaraemia in any of the study communities. The
      observed patterns of microfilaraemia and the lack of obvious visible clinical
      manifestations suggest that the host's regulatory responses are downregulated in
      M. perstans infections. [ClinicalTrials.gov identifier: NCT00215280].

PMID- 18809193
TI  - Antigenemia in young children living in Wuchereria bancrofti-endemic areas of
      Orissa, India.
AB  - The prevalence of filarial antigenemia (an indicator of adult worm burden) among
      610 children, aged 3-15 years, was determined in three endemic villages of Khurda
      District, Orissa, India, during 2005. Prevalence of antigenemia, detected using
      Og4C3 circulating filarial antigen ELISA, was 32.6% compared with 10%
      microfilaraemia. Although the prevalence of antigenemia increased marginally with
      increase in age, no significant difference was observed among the children of
      different age groups (28.3% in 3-5 years, 31.5% in 6-10 years and 35.2% in 11-15
      years), indicating that the adult worm burdens did not vary much according to the
      age of the study children. Gender did not influence the prevalence of
      antigenemia. The study emphasizes the advantage of using the circulating filarial
      antigen assay for detecting true filarial infection and demonstrates a high
      prevalence of antigenemia among the 610 children studied.

PMID- 18809194
TI  - Links between diabetes mellitus and tuberculosis: should we integrate screening
      and care?
AB  - Recent systematic reviews show that diabetes mellitus (DM) increases the risk and
      odds of developing tuberculosis (TB), especially in young people and in
      developing countries with a high background incidence of TB. There are no data
      showing that TB increases the risk of DM. The large dual burden of disease may
      make management of both conditions more difficult. High-quality implementation
      research is needed to assess the value and ways of screening for DM in patients
      with TB and vice versa, and to set up standardised systems of monitoring and
      evaluation based on the directly observed treatment, short-course (DOTS) model
      used for TB control.

PMID- 18809195
TI  - Selective regimes and evolutionary rates of HIV-1 subtype B V3 variants in the
      Brazilian epidemic.
AB  - Half of subtype B Brazilian HIV-1 harbors the V3 tip GWGR instead of the GPGR. To
      investigate the evolution of GW variants, we analyzed 81 env sequences and 5 full
      length GW genomes from antiretroviral-naive individuals sampled between 1983 and
      1999. Phylogenetic analysis indicated that GW strains intermingle in the tree
      with other subtype B sequences. The mean d(N)/d(S) values of GW strains were
      proximal to those of the other sequences, regardless of sampling years or
      clinical status. In sequences from patients with CD4+ T cell counts >or=200
      cells/microL, the mean d(N)/d(S) ratio was greater than one, suggesting a
      positive selection. The prevalence of GW variants was lower among individuals in
      whom disease progressed. This is probably attributable to the fact that
      tryptophan is replaced by other amino acids over time, whereas the GP motif does
      not evolve as rapidly.

PMID- 18809196
TI  - Manganese removal during bench-scale biofiltration.
AB  - As biological manganese (Mn) removal becomes a more popular water treatment
      technology, there is still a large gap in understanding the key mechanisms and
      range of operational characteristics. This research aimed to expand on previous
      bench-scale experiments by directly comparing small filtration columns inoculated
      with indigenous biofilms from a Mn filtration plant and filtration columns
      inoculated with a liquid suspension of Leptothrix discophora SP-6. Batch tests
      found that in the absence of manganese oxidizing bacteria Mn was not removed by
      air alone, whereas a mixed population and Leptothrix strain achieved greater than
      90% removal of Mn. The bench-scale biofiltration experiments found that
      biological filters can be inoculated with a pure culture of L. discophora SP-6
      and achieve a similar removal of indigenous biofilm. While Mn oxidizing bacteria
      (MOB) seem to be necessary for the auto-catalytic nature of these biological
      filters, Mn removal is achieved with a combination of adsorption to Mn oxides and
      biological oxidation. Additionally, it was demonstrated that biological Mn
      removal is possible over a broader "field of activity" (e.g., Mn removal occurred
      at a pH level as low as 6.5) than has previously been reported. The ability of
      this treatment technology to work over a broader range of influent conditions
      allows for more communities to consider biological treatment as an option to
      remove Mn from their drinking water.

PMID- 18809197
TI  - Alanine-dependent reactions of 5'-deoxypyridoxal in water.
AB  - The non-enzymatic reaction of 5'-deoxypyridoxal (DPL) with l-alanine in water at
      25 degrees C was investigated. DPL reacts with alanine to form an imine, which
      then undergoes deprotonation at the alpha-amino carbon of alanine to form a
      resonance delocalized DPL-stabilized carbanion. At early reaction times the only
      detectable products are pyruvate and the dimeric species formed by addition of
      the alpha-pyridine stabilized carbanion to DPL. No Claisen-type products of
      addition of the alpha-amino carbanion to DPL, as was previously reported to form
      from the reaction between DPL and glycine [K. Toth, T.L. Amyes, J.P. Richard,
      J.P.G. Malthouse, M.E. Ni Beilliu, J. Am. Chem. Soc. 126 (2004) 10538-10539], are
      observed. The electrophile reacts instead at the alpha-pyridyl carbon. This dimer
      is in chemical equilibrium with reactants. At longer reaction times about 50% of
      DPL is converted to 5'-deoxypyridoxamine, the thermodynamically favored product
      of formal transamination of DPL.

PMID- 18809198
TI  - Histopathological and biochemical evidence of hepatopancreatic toxicity caused by
      cadmium and zinc in the white shrimp, Litopenaeus vannamei.
AB  - The white shrimp, Litopenaeus vannamei, a globally important cultured prawn
      species, is an ideal animal for studying the impairment caused by the effects of
      heavy metals that are often detected in coastal areas. In this study, L. vannamei
      was exposed to different concentrations of cadmium (Cd) and zinc (Zn) for up to
      28 d. Histopathological alterations in the hepatopancreas were observed in L.
      vannamei after long-term exposure to Cd and Zn. Hepatopancreatic injury was
      further confirmed by the inductions of two biochemical markers, hemolymphatic
      glutamate-oxalacetate transaminase (GOT) and glutamate-pyruvate transaminase
      (GPT). It was notable that L. vannamei was able to repair its hepatopancreas from
      the damage caused by Zn, which was evidenced by the results of the
      histopathological observations, determinations of tissue metal concentrations,
      and examination of GOT and GPT levels.

PMID- 18809199
TI  - Reduction of chlorinated methanes with nano-scale Fe particles: effects of
      amphiphiles on the dechlorination reaction and two-parameter regression for
      kinetic prediction.
AB  - The influences of amphiphiles, including humic acid (HA) and various types of
      surfactants, on dechlorination of carbon tetrachloride (CTC) and chloroform (CF)
      by the nano-scale Fe particles were investigated. Since the amphiphiles would
      modify the surface tension between the liquid-liquid and solid-liquid interface,
      in the presence of amphiphile matrix solution the Fe corrosion rate and the
      parent compound dechlorination rate would be different from those in the
      ultrapure water. Among the four amphiphile solutions, Fe corrosion rate was the
      highest in the anionic surfactant sodium dodecyl sulfate (SDS) solution,
      presumably due to the existence of chemisorption between the hydrophilic head of
      SDS and Fe particles. The dechlorination rates of CTC and CF could be described
      with the pseudo-first order kinetic model. The influences of amphiphiles on the
      dechlorination reaction rate were related to the species of parent compound and
      concentration of the matrix solution. The influences of HA on the dechlorination
      of CTC and CF were the most significant compared to other matrix solutions. At
      relatively low HA concentration (<0.1 g L(-1)), the HA molecules (serving as
      electron transfer mediator) would significantly accelerate the dechlorination
      rate of CF. The two-parameter regression with energy of the lowest unoccupied
      molecular orbital (E(LUMO)) and HA concentration as the descriptors was developed
      to predict the specific reduction rate constants of chlorinated methanes in HA
      solution. The analysis of variance (ANOVA) indicated the existence of significant
      relationship between the dechlorination rate constants and the two descriptors.

PMID- 18809200
TI  - Study on reaction kinetics and selective precipitation of Cu, Zn, Ni and Sn with
      H2S in single-metal and multi-metal systems.
AB  - Determination of reaction kinetics and selective precipitation of Cu, Zn, Ni and
      Sn with H(2)S in single-metal and multi-metal systems were studied to develop a
      process of metal recovery from plating wastewater. As samples, single-metal model
      wastewaters containing Cu, Sn, Zn or Ni, and multi-metal model wastewater
      containing Cu-Zn-Ni or Sn-Zn mixtures were used. In both single-metal and multi
      metal systems, the pH value was precisely controlled at a value of 1.5 for CuS
      and SnS precipitation, 4.5 for ZnS precipitation and 6.5-7.0 for NiS
      precipitation. Subsequently, the sulfidation of Cu, Sn, Zn and Ni was evaluated.
      It was found that an amount of H(2)S equimolar to a given metal was sufficient to
      achieve almost complete precipitation of the particular metal. Further, the
      selectivity of metal precipitation was found to be higher than 95% in the Cu-Zn
      Ni multi-metal system and higher than 91% in the Sn-Zn system. It was also found
      that the sulfidation reaction proceeded in accordance with Higbie's penetration
      theory and reaction rate constants and mass-transfer coefficients under various
      experimental conditions were determined. Finally, the reaction rate constants
      obtained in single-metal and multi-metal systems were found to be almost the same
      indicating that the precipitation of a particular metal was not significantly
      affected by the presence of other components.

PMID- 18809202
TI  - The Movius Line sensu lato (Norton et al., 2006) further assessed and defined.

PMID- 18809203
TI  - Evolutionary modifications of human milk composition: evidence from long-chain
      polyunsaturated fatty acid composition of anthropoid milks.
AB  - Brain growth in mammals is associated with increased accretion of long-chain
      polyunsaturated fatty acids (LCPUFA) in brain phospholipids. The period of
      maximum accumulation is during the brain growth spurt. Humans have a perinatal
      brain growth spurt, selectively accumulating docosahexaenoic acid (DHA) and other
      LCPUFA from the third trimester through the second year of life. The emphasis on
      rapid postnatal brain growth and LCPUFA transfer during lactation has led to the
      suggestion that human milk LCPUFA composition may be unique. Our study tests this
      hypothesis by determining fatty acid composition for 11 species of captive
      anthropoids (n=53; Callithrix jacchus, Cebus apella, Gorilla gorilla, Hylobates
      lar, Leontopithecus rosalia, Macaca mulatta, Pan troglodytes, Pan paniscus, Pongo
      pygmaeus, Saimiri boliviensis, and Symphalangus syndactylus). Results are
      compared to previously published data on five species of wild anthropoids (n=28;
      Alouatta paliatta, Callithrix jacchus, Gorilla beringei, Leontopithecus rosalia,
      and Macaca sinica) and human milk fatty acid profiles. Milk LCPUFA profiles of
      captive anthropoids (consuming diets with a preformed source of DHA) are similar
      to milk from women on a Western diet, and those of wild anthropoids are similar
      to milk from vegan women. Collectively, the range of DHA percent composition
      values from nonhuman anthropoid milks (0.03-1.1) is nearly identical to that from
      a cross-cultural analysis of human milk (0.06-1.4). Humans do not appear to be
      unique in their ability to secrete LCPUFA in milk but may be unique in their
      access to dietary LCPUFA.

PMID- 18809204
TI  - Ultra-fine particles release from hardcopy devices: sources, real-room
      measurements and efficiency of filter accessories.
AB  - The release of ultra-fine particles (UFP, d < 0.1 microm) from hardcopy devices
      such as laser printers into the indoor environment is currently a topic of high
      concern. The general emission behavior of a printer can be examined by conducting
      emission test chamber measurements with particle-counting devices. Chamber
      experiments with modified laser printers operated without toner or paper also
      revealed UFP emissions. On the basis of these results we reasonably doubt the
      opinion that UFPs primarily originate from the toner. Instead, the high
      temperature fuser unit is assumed to be one source for ultra-fine particle
      emission. UFP release typically follows the flow path of the cooling air which
      may leave the printer casing at various points (e.g. the paper tray). This limits
      the usability of the commercial filter systems available because the released
      particles could leave the printer without passing through the filter. Chamber
      measurements with various filter systems retrofitted to a laser printer
      demonstrate different efficiencies of UFP reduction. Complementary experiments
      were carried out in an office room. Here the decay of the particle concentration
      after a print job was about ten times slower than in the test chamber. A
      toxicological assessment of the emitted particles requires that their chemical
      composition be known. Due to the low mass of the released UFPs chemical analysis
      needs a prior enrichment on a feasible media. Experiments using electrostatic
      precipitation showed a flame retardant (tri-xylyl phosphate) whose concentration
      on the media was dependent on the number of pages printed. Whether this compound
      was particle-bound could not be determined.

PMID- 18809205
TI  - Oral anticoagulant therapy for patients with atrial fibrillation--an update.

PMID- 18809206
TI  - Low-molecular-weight heparin use in the obese, elderly, and in renal
      insufficiency.
AB  - Superior bioavailability and simple weight-based dosing have made low-molecular
      weight heparins (LMWH) the preferred agents for treatment and prevention of
      venous thromboembolism (VTE) for most indications. Despite improved
      pharmacokinetics, there remain populations where appropriate LMWH dose intensity
      and frequency are open to question. Obese patients have a lower proportion of
      lean body mass as a percentage of total body weight. As a result, LMWH dosing
      based on total body weight could cause supra-therapeutic anticoagulation. Elderly
      patients also have less lean body mass in addition to a higher incidence of age
      related renal disease and increased risk of bleeding. Renal insufficiency
      presents a risk of LMWH accumulation as well as increased risk of bleeding. Among
      LMWH products, only dalteparin labeling recommends a maximum dose. Prospective
      data call into question the validity of this dose limitation. Additionally,
      because obese patients are already at higher risk of VTE recurrence, they may be
      particularly sensitive to subtherapeutic anticoagulation. Prospective data
      evaluating LMWH use in elderly patients have been limited to in-patient
      treatment. Few recommendations can be made in this population other than close
      monitoring. Renal insufficiency is a risk for bleeding during LMWH use. Available
      evidence supports the potential for enoxaparin accumulation, but not tinzaparin.
      Enoxaparin dose adjustment, either empiric or based on anti-Xa monitoring, has
      insufficient data to support widespread implementation. Unfractionated heparin is
      not reliant on renal elimination and is a sensible option for VTE treatment in
      patients with a creatinine clearance<30 ml/min.

PMID- 18809207
TI  - Low peripheral progesterone and late embryonic/early fetal loss in suckled beef
      and lactating dairy cows.
AB  - Pregnancy failure during placentation in lactating dairy cows was associated with
      low concentrations of serum progesterone. Beef cows have greater serum
      progesterone and less pregnancy failure. Experiment 1 determined that reduction
      of serum progesterone affected late embryonic/early fetal loss in suckled beef
      cows. Cows (n=40) received progesterone from two new or used controlled internal
      drug releasing devices, replaced every 5d, beginning on Day 28 of gestation
      (mating=Day 0); CL were enucleated on Day 29. Retention of pregnancy was 77% in
      treated cows and 97% in 78 control cows (P<0.05). Experiment 2 determined how
      pregnant, lactating dairy cows with high or low progesterone concentrations
      during Days 28-34 differed in luteal function or in serum progesterone during
      replacement therapy. Luteal tissue from such cows was assayed for progesterone
      and expression of mRNA for genes of endothelin and prostaglandin (PG) systems.
      Secretion of progesterone and prostaglandins by dispersed luteal cells was
      determined during incubation with LH, endothelin-1, or arachidonic acid. Neither
      luteal progesterone nor mRNAs for endothelin or prostaglandin systems differed.
      Endothelin-1 inhibited secretion of progesterone more (P<0.05) in luteal cells
      from cows with low versus high serum progesterone, when incubated with
      arachidonic acid. Secretion of prostaglandin F(2)alpha was increased and that of
      6-keto-PGF(1)alpha decreased by endothelin-1 in vitro. Serum progesterone during
      replacement was lower (P<0.05) for cows with low than high serum progesterone at
      lutectomy. Thus, clearance, more than luteal production, determined peripheral
      progesterone in pregnant, lactating dairy cows.

PMID- 18809208
TI  - Release of calcitonin gene-related peptide from the jugular-nodose ganglion
      complex in rats--a new model to examine the role of cardiac peptidergic and
      nitrergic innervation.
AB  - OBJECTIVE: Afferent information from the heart and the lung is conveyed to the
      brainstem by primary afferent fibers originating from vagal sensory neurons
      (jugular-nodose ganglion complex, JNC). The present study was made to evaluate if
      release of the sensory neuropeptide calcitonin gene-related peptide (CGRP) from
      the JNC can be used as a model for future studies on changes in neuropeptide
      release under pathological conditions of the heart. METHODS: Freshly isolated rat
      JNC's were passed through a series of solutions based on oxygenated synthetic
      interstitial fluid (SIF). Substances such as the TRPV1 receptor agonist capsaicin
      and the nitric oxide (NO) donor sodium nitroprusside (SNP) were added as
      excitatory test stimuli. The eluates were processed using an enzyme immuno-assay
      (EIA) for measurement of CGRP concentrations. Immunohistochemistry was used to
      visualize CGRP containing and NO producing neurons in the JNC. RESULTS: Both SNP
      and capsaicin caused significant increases in CGRP release. CGRP-immunoreactive
      neurons (somata) were preferentially found in the jugular ganglion, whereas
      neurons immunoreactive for neuronal NO synthase were mostly localized in the
      nodose ganglion. CONCLUSION: The present study demonstrates an easily
      reproducible model for measuring stimulated CGRP release from vagal afferents
      arising from the JNC. Nitric oxide produced by vagal afferents may stimulate CGRP
      release upon afferent activation.

PMID- 18809209
TI  - Molecular typing and antimicrobial resistance of Salmonella enterica subspecies
      enterica serovar Choleraesuis isolates from diseased pigs in Japan.
AB  - Salmonella enterica serovar Choleraesuis (S. Choleraesuis) isolates derived from
      diseased pigs in Japan during 2001 and 2005 were analyzed for biotype, based on
      H(2)S production and dulcitol fermentation, pulsed-field gel electrophoresis
      (PFGE) profile, and antimicrobial resistance profile. S. Choleraesuis biotype
      Choleraesuis (biotype Choleraesuis) was classified into one genotype, while
      varietas Kunzendorf (var. Kunzendorf) was classified into two genotypes. The
      isolates of var. Kunzendorf belonging to one genotype were isolated in a limited
      area of Japan. Variation in the antimicrobial resistance pattern was observed in
      isolates of both biotypes Choleraesuis and var. Kunzendorf. We have also shown
      that the PFGE profile was associated with the biotype and isolation region of
      each isolate.

PMID- 18809210
TI  - Physical victimization in prison: the role of mental illness.
AB  - This study compares prison physical victimization rates (inmate-on-inmate and
      staff-on-inmate) for people with mental disorder to those without mental disorder
      in a state prison system. Inmate subjects were drawn from 14 adult prisons
      operated by a single mid-Atlantic State. A sample of 7,528 subjects aged 18 or
      older (7,221 men and 564 women) completed an audio-computer administered survey
      instrument. Mental disorder was based on self-reported mental health treatment
      ever for particular mental disorders. Approximately one-quarter of the sample
      reported some prior treatment for schizophrenia, bipolar disorder, depression,
      PTSD, or anxiety disorder. Rates of physical victimization for males with any
      mental disorder were 1.6 times (inmate-on-inmate) and 1.2 times (staff-on-inmate)
      higher than that of males with no mental disorder. Female inmates with mental
      disorder were 1.7 times more likely to report being physically victimized by
      another inmate than did their counterparts with no mental disorder. Overall, both
      males and females with mental disorder are disproportionately represented among
      victims of physical violence inside prison.

PMID- 18809211
TI  - Contamination of groundwater and risk assessment for arsenic exposure in Ha Nam
      province, Vietnam.
AB  - The characteristics of arsenic-contaminated groundwater and the potential risks
      from the groundwater were investigated. Arsenic contamination in groundwater was
      found in four villages (Vinh Tru, Bo De, Hoa Hau, Nhan Dao) in Ha Nam province in
      northern Vietnam. Since the groundwater had been used as one of the main drinking
      water sources in these regions, groundwater and hair samples were collected in
      the villages. The concentrations of arsenic in the three villages (Vinh Tru, Bo
      De, Hoa Hau) significantly exceeded the Vietnamese drinking water standard for
      arsenic (10 microg/L) with average concentrations of 348, 211, and 325 microg/L,
      respectively. According to the results of the arsenic speciation testing, the
      predominant arsenic species in the groundwater existed as arsenite [As(III)].
      Elevated concentrations of iron, manganese, and ammonium were also found in the
      groundwater. Although more than 90% of the arsenic was removed by sand filtration
      systems used in this region, arsenic concentrations of most treated groundwater
      were still higher than the drinking water standard. A significant positive
      correlation was found between the arsenic concentrations in the treated
      groundwater and in female human hair. The risk assessment for arsenic through
      drinking water pathways shows both potential chronic and carcinogenic risks to
      the local community. More than 40% of the people consuming treated groundwater
      are at chronic risk for arsenic exposure.

PMID- 18809212
TI  - Constitutive expression of the antibacterial CXC chemokine GCP-2/CXCL6 by
      epithelial cells of the male reproductive tract.
AB  - The reproductive tract is continuously challenged by potential pathogens present
      in the environment. Therefore, robust host defense mechanisms are essential both
      for the health of the individual and for fertilization. Antibiotic innate
      immunity peptides possess broad antimicrobial activity. Recently, we found that
      the CXC chemokine, granulocyte chemotactic protein (GCP)-2/CXCL6, possesses
      antibacterial activity. In the present study, we investigated, therefore, the
      presence of GCP-2/CXCL6 in the human male reproductive system. GCP-2/CXCL6 was
      detected at 19nM (mean; range: 5-47nM; n=14) in seminal plasma of fertile donors,
      i.e. at levels more than 100 times higher than those previously reported for the
      related chemokine IL-8/CXCL8. No GCP-2/CXCL6 could be detected in blood plasma of
      healthy donors, indicating local production in the male reproductive tract. In
      vasectomized donors, significantly lower levels of GCP-2/CXCL6 were found (mean:
      3nM; range 2-7nM; n=7), demonstrating that the testis and epididymis contribute
      significantly to the GCP-2/CXCL6 content of seminal plasma. Strong expression of
      GCP-2/CXCL6 was found in the epithelium of the testis, epididymis and seminal
      vesicles, while the prostate epithelium showed weak expression, as determined by
      immunohistochemistry. A biological function is suggested, viz. at concentrations
      of the order of those found in seminal plasma, GCP-2/CXCL6 has antibacterial
      activity against the urogenital pathogen Neisseria gonorrhoeae. GCP-2/CXCL6 in
      seminal plasma may play roles in both host defense of the male urogenital tract
      and during fertilization.

PMID- 18809213
TI  - Lambert-eaton myasthenic syndrome differential reactivity of tumor versus non
      tumor patients to subunits of the voltage-gated calcium channel.
AB  - OBJECTIVE: Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disease in
      which the transmission across the neuromuscular junction is disturbed by
      autoantibodies directed against the presynaptic P/Q-type voltage-gated calcium
      channels (VGCC). LEMS is paraneoplastic (T-LEMS) in about 60% of patients mostly
      associated with a small cellular lung carcinoma (SCLC), but occurs spontaneously
      without a tumor in 40% (NT-LEMS). In most cases neurologic symptoms appear before
      tumor diagnosis, but there is as yet no clear specific serologic marker to
      distinguish between NT- and T-LEMS. METHODS: To see whether antibodies from
      patients with NT- and T-LEMS differentially recognize antigenic sites of the
      alpha 1A subunit of P/Q-type VGCC, we studied serum samples from 22 T-LEMS and 24
      NT-LEMS patients. Sera reactivity was tested by Western blot analysis to
      recombinant proteins corresponding to the extracellular S5-S6 linker region of
      three out of four domains forming the alpha 1 subunit of P/Q-type VGCC. RESULTS:
      Sera from 9/24 (37,5%) NT-LEMS patients, but only 1/22 (4,6%) T-LEMS patients
      recognized domain IV (p=0,011). Seroreactivity to domains I and III was similar
      for NT-LEMS and T-LEMS patients (domain I: 8%/14%; domain III: 46%/41%, not
      significant). CONCLUSIONS: These data suggest that an antibody response to domain
      IV is more common in LEMS without tumor than in paraneoplastic LEMS. This may
      have implications for diagnostic workup in LEMS patients without previously
      established diagnosis of a tumor. Additionally this could point towards a
      differential autoimmune pathogenesis between T-LEMS and NT-LEMS.

PMID- 18809214
TI  - Absence of GJB3 and GJB6 mutations in Moroccan familial and sporadic patients
      with autosomal recessive non-syndromic deafness.
AB  - Deafness is an etiologically heterogeneous trait with a wide variety of genetic
      and environmental causes. It is generally considered that genetic factors account
      for at least half of all cases of profound congenital deafness, which can be
      classified in two categories - dominant or recessive - according to the mode of
      inheritance and in two types - syndromic or non-syndromic - according to the
      presence or absence of some other specific clinical features. Mutations in the
      gene GJB2, encoding the gap junction protein connexion 26, are considered to be
      responsible for up to 50% of familial cases of autosomal recessive non-syndromic
      hearing loss and for up to 15-30% of the sporadic cases. It has also been
      reported that mutations in the GJB6 and GJB3 genes contribute to autosomal
      recessive and autosomal dominant hearing defects in many populations. OBJECTIVE:
      The aim of this study was to screen mutations in GJB6 and GJB3 genes in Moroccan
      patients with autosomal non-syndromic hearing loss. METHODS: We carried out 95
      patients with non-syndromic hearing loss. The patients, who were negative for
      homozygous mutations in GJB2 gene and GJB6-D13S1830 deletion, were tested for the
      coding regions of GJB6 and GJB3 genes by direct sequencing. RESULTS: No
      deleterious mutation in GJB6 and GJB3 genes was detected in all deaf patients
      tested. Only a C357T silent transition in heterozygous state was found in the
      GJB3 gene in one patient. CONCLUSION: The present data demonstrated that
      mutations in the GJB6 and GJB3 genes are an infrequent cause of non-syndromic
      deafness in Morocco.

PMID- 18809215
TI  - Sudden hearing loss in a family with GJB2 related progressive deafness.
AB  - Mutations of GJB2, the gene encoding connexin 26, have been associated with
      prelingual, sensorineural hearing loss of mild to profound severity. One specific
      mutation, the 35delG, has accounted for the majority of mutations detected in the
      GJB2 gene in Caucasian populations. Recent studies have described progression of
      hearing loss in a proportion of cases with GJB2 deafness. We report an unusual
      family with four 35delG homozygous members, in which the parents were deaf-mute
      whilst both children had a postlingual progressive hearing loss. Furthermore, the
      son suffered from sudden hearing loss.

PMID- 18809216
TI  - The model anti-androgen flutamide suppresses the expression of typical male
      stickleback reproductive behaviour.
AB  - Over the past 15 years considerable attention has been given to the presence in
      the environment of endocrine disrupting chemicals (EDCs) that may have harmful
      effects on organisms. Specific test guidelines for the detection of EDCs used for
      short-term fish screening assays have been developed by the Organisation for
      Economic Cooperation and Development (OECD). Compared to the core species used in
      the OECD guidelines, the three-spined stickleback (Gasterosteus aculeatus) has an
      additional and unique endpoint for (anti-)androgenic substances through the
      androgen-dependent glue protein (spiggin) used in the nest building. Here we
      describe a specific behavioural assay that was developed in parallel to the OECD
      protocol, utilising unique behavioural features of sticklebacks. In the assay, a
      photoperiod of 16L:8D (light:dark) and a temperature of 17+/-1 degrees C was used
      to induce breeding in quiescent male sticklebacks that were simultaneously
      exposed for a 21-day period to the mammalian anti-androgen flutamide (FL) at 100,
      500 and 1000 microg/l (plus a water control). Spiggin production and the
      reproductive behaviour (nest building and courtship) of male sticklebacks were
      the main measured endpoints. The control fish entered an active breeding cycle
      including nest building and courtship behaviours as expected due to the
      stimulating temperature and photoperiodic conditions. The FL-exposed males showed
      significantly lower spiggin levels at 500 and 1000 microg/l. In addition, there
      was a significant decrease in the number of nests built by the FL-treated males
      at 100 microg/l with no nest built at 500 and 1000 microg/l. Finally, FL affected
      the courtship behaviour of the males with a significant reduction of the number
      of zigzags towards the female. When the breeding status of the stickleback males
      is controlled, the behavioural assay developed here is a suitable tool for the
      detection of androgen antagonists.

PMID- 18809217
TI  - Pioglitazone reduces tumor necrosis factor-alpha serum concentration and mRNA
      expression of adipose tissue in hypercholesterolemic rabbits.
AB  - BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) is an inflammatory cytokine
      involved in atherogenesis. Adipose tissue is an important source of endogenous
      TNF-alpha production. Pioglitazone, a member of the thiazolidinediones (TZDs),
      has anti-inflammatory and anti-atherogenic properties, while underlying mechanism
      has not been fully elucidated. The aim of this study was to evaluate the effect
      of pioglitazone on TNF-alpha serum concentration and mRNA expressions of
      subcutaneous adipose tissue in hypercholesterolemic rabbits. METHODS: Ten rabbits
      fed with high-cholesterol diet for 8 weeks were randomly divided into two groups:
      (1) high cholesterol group (n=5): maintained high cholesterol diet for 4 weeks;
      (2) pioglitazone group (n=5): the same cholesterol diet plus pioglitazone (3
      mg/kg/day) for 4 weeks. Control group (n=5) was fed with normal diet for 12
      weeks. Subcutaneous adipose tissue was collected for RNA analysis. The direct
      effect of pioglitazone on TNF-alpha release was assayed in primary rabbit
      adipocytes. TNF-alpha levels in serum and adipocytes culture supernatant were
      measured by ELISA. RT-PCR was used to evaluate TNF-alpha mRNA expressions in
      adipose tissue and adipocytes. RESULTS: Compared with control group, rabbits fed
      with high cholesterol diet showed significantly higher levels of serum total
      cholesterol (TC), low density lipoprotein cholesterol (LDL-C) and TNF-alpha.
      Though having no effect on serum glucose level and lipid profile, pioglitazone
      administration significantly reduced circulating TNF-alpha concentrations, which
      were positively correlated with TNF-alpha mRNA expressions of adipose tissue
      (r=0.53, P<0.01). Pioglitazone dose-dependently inhibited lipopolysaccharide
      (LPS)-induced TNF-alpha secretion and mRNA expression in cultured adipocytes.
      CONCLUSION: Pioglitazone significantly reduced serum TNF-alpha level in
      hypercholesterolemic rabbits independent of its metabolic actions, which may at
      least partly be due to its direct inhibition of TNF-alpha expression and
      secretion of adipocytes. This may help to explain the mechanism by which
      pioglitazone exert anti-atherosclerotic effects.

PMID- 18809218
TI  - Myocardial injection of skeletal myoblasts impairs contractility of host
      cardiomyocytes.
AB  - BACKGROUND: Mechanisms underlying improvement of myocardial contractile function
      after cell therapy as well as arrhythmic side effect remain poorly understood. We
      hypothesised that cell therapy might affect the mechanical properties of isolated
      host cardiomyocytes. METHODS: Two weeks after myocardial infarction (MI), rats
      were treated by intramyocardial myoblast injection (SkM, n=8), intramyocardial
      vehicle injection (Medium, n=6), or sham operation (Sham, n=7). Cardiac function
      was assessed by echocardiography. Cardiomyocytes were isolated in a modified
      Langendorff perfusion system, their contraction was measured by video-based inter
      sarcomeric analysis. Data were compared with a control-group without myocardial
      infarction (Control, n=5). RESULTS: Three weeks post-treatment, ejection fraction
      (EF) further deteriorated in vehicle-injected and non-injected rats (respectively
      40.7+/-11.4% to 33+/-5.5% and 41.8+/-8% to 33.5+/-8.3%), but was stabilised in
      SkM group (35.9+/-6% to 36.4+/-9.7%). Significant cell hypertrophy induced by MI
      was maintained after cell therapy. Single cell contraction (dL/dt(max)) decreased
      in SkM and vehicle groups compared to non-injected group as well as cell
      shortening and relaxation (dL/dt(min)) in vehicle group. A significantly
      increased predisposition for alternation of strong and weak contractions was
      observed in isolated cardiomyocytes of the SkM group. CONCLUSION: Our study
      provides the first evidence that injection of materials into the myocardium
      alters host cardiomyocytes contractile function independently of the global
      beneficial effect of the heart function. These findings may be important in
      understanding possible adverse effects.

PMID- 18809219
TI  - Lytic activity of the recombinant staphylococcal bacteriophage PhiH5 endolysin
      active against Staphylococcus aureus in milk.
AB  - The endolysin gene (lysH5) from the genome of the Staphylococcus aureus
      bacteriophage PhiH5 was cloned in Escherichia coli and characterized. The lysH5
      gene encoded a protein (LysH5) whose calculated molecular mass and pI were 53.7
      kDa and 8.7, respectively. Comparative analysis revealed that LysH5 significantly
      resembled other murein hydrolases encoded by staphylococcal phages. The modular
      organization of LysH5 comprised three putative domains, namely, CHAP (cysteine,
      histidine-dependent amidohydrolase/peptidase), amidase (L-muramoyl-L-alanine
      amidase), and SH3b (cell wall recognition). In turbidity reduction assays, the
      purified protein lysed bovine and human S. aureus, and human Staphylococcus
      epidermidis strains. Other bacteria belonging to different genera were not
      affected. The lytic activity was optimal at pH 7.0, 37 degrees C, and sensitive
      to high temperatures. The purified protein was able to kill rapidly S. aureus
      growing in pasteurized milk and the pathogen was not detected after 4 h of
      incubation at 37 degrees C. As far as we know, this is the first report to assess
      the antimicrobial activity of a phage endolysin which might be useful for novel
      biocontrol strategies in dairying.

PMID- 18809220
TI  - Time-dependent persistence of enhanced immune response by a potential probiotic
      strain Lactobacillus paracasei subsp. paracasei NTU 101.
AB  - The possible time-dependent role of lactic acid bacteria (LAB) in
      immunomodulation was investigated in BALB/c mice fed daily with Lactobacillus
      paracasei subsp. paracasei NTU 101 (10(8) colony forming units) for 3, 6, and 9
      weeks, and following feeding with Lactobacillus-free food for a further 7 days.
      We observed up-regulation of the antigen-presenting ability of dendritic cells,
      and expression of natural killer group-2 D (NKG2D) molecules capable of trigger
      natural killer cell-mediated cytotoxicity. Lymphocyte proliferation and antibody
      production were also significantly increased in mice after treatment. Innate and
      adaptive immunity remained constant even at the most protracted feeding time,
      indicative of the time dependence of the bacterial-mediated enhanced immunity. To
      better correlate intestinal microflora with immunity, the intestinal contents of
      probiotics and harmful microorganisms were determined. Results showed an altered
      intestinal microflora, with increases in bifidobacteria and lactobacilli and a
      decreased content of Clostridium perfringens after feeding with L. paracasei
      subsp. paracasei NTU 101. It is possible that persistent activation of immunity
      might be induced by intestinal probiotics.

PMID- 18809221
TI  - The active metabolite of leflunomide, A77 1726, protects rat hepatocytes against
      bile acid-induced apoptosis.
AB  - BACKGROUND/AIMS: Leflunomide is used in the treatment of autoimmune diseases as
      an anti-inflammatory agent. Leflunomide and its active metabolite A77 1726
      modulate mitogen-activated protein kinases (MAPK), Src kinases, the
      phosphoinositide-3 kinase (PI3K)/Akt-pathway and nuclear factor (NF)-kappaB
      activation. Both cell protective and cytotoxic effects of leflunomide have been
      described. Since leflunomide affects pathways involved in hepatocyte cell
      survival, we examined the effects of A77 1726 on hepatocyte cell death. METHODS:
      Primary rat hepatocytes were exposed to the bile acid glycochenodeoxycholic acid
      (GCDCA), the superoxide anion donor menadione, or tumor necrosis factor (TNF)
      alpha in combination with actinomycin D. Activation of MAP-kinases was determined
      by Western blot analysis. Apoptosis and necrosis were analyzed by acridine orange
      staining and caspase activity and Sytox Green staining, respectively. RESULTS:
      A77 1726 dose-dependently reduces GCDCA-induced apoptosis and necrosis, but not
      menadione- or TNFalpha/ActD-induced apoptosis. The hepatoprotective effect of A77
      1726 does not involve ERK1/2, p38 or PI3K/Akt activation. A77 1726 does not
      inhibit NF-kappaB activation in hepatocytes. CONCLUSIONS: Since A77 1726 inhibits
      bile acid-induced apoptosis and does not sensitize hepatocytes to TNFalpha, our
      results suggest that A77 1726 could be considered for the treatment of chronic
      liver diseases accompanied by elevated bile acid levels and inflammation.

PMID- 18809223
TI  - Expression of apolipoprotein C-IV is regulated by Ku antigen/peroxisome
      proliferator-activated receptor gamma complex and correlates with liver
      steatosis.
AB  - BACKGROUND/AIMS: We previously reported that hepatitis C virus (HCV) core protein
      up regulated transcription of apolipoprotein C-IV (ApoC-IV, 10.7-fold increase),
      a member of the apolipoprotein family implicated in liver steatosis. Here, we
      identified host transcription factors regulating the ApoC-IV gene expression.
      METHODS: Transcriptional regulators were identified by DNA affinity purification
      and steatosis was detected by oil red O staining and triglyceride assay. RESULTS:
      We defined a 163-bp ApoC-IV promoter as a core protein responsive element, and
      identified Ku antigen complex (Ku70 and Ku80) as well as nuclear receptors
      PPARgamma/RXRalpha as key regulators of ApoC-IV gene expression. Both Ku70
      overexpression and PPARgamma agonist significantly increased ApoC-IV promoter
      activity; conversely, Ku70 silencing or mutation of PPARgamma binding site
      diminished the ApoC-IV promoter activity. Interestingly, transient transfection
      of ApoC-IV cDNA into a human hepatoma cell line was able to trigger moderate
      lipid accumulation. In agreement with this in vitro study, ApoC-IV transcript
      level was increased in HCV infected livers which correlated with triglyceride
      accumulation. CONCLUSIONS: ApoC-IV overexpression may perturb lipid metabolism
      leading to lipid accumulation. HCV core protein may modulate ApoC-IV expression
      through Ku antigen and PPARgamma/RXRalpha complex.

PMID- 18809224
TI  - MMEJ repair of double-strand breaks (director's cut): deleted sequences and
      alternative endings.
AB  - DNA double-strand breaks are normal consequences of cell division and
      differentiation and must be repaired faithfully to maintain genome stability. Two
      mechanistically distinct pathways are known to efficiently repair double-strand
      breaks: homologous recombination and Ku-dependent non-homologous end joining.
      Recently, a third, less characterized repair mechanism, named microhomology
      mediated end joining (MMEJ), has received increasing attention. MMEJ repairs DNA
      breaks via the use of substantial microhomology and always results in deletions.
      Furthermore, it probably contributes to oncogenic chromosome rearrangements and
      genetic variation in humans. Here, we summarize the genetic attributes of MMEJ
      from several model systems and discuss the relationship between MMEJ and
      'alternative end joining'. We propose a mechanistic model for MMEJ and highlight
      important questions for future research.

PMID- 18809225
TI  - Lung cancer patients who are asymptomatic at diagnosis show favorable prognosis:
      a korean Lung Cancer Registry Study.
AB  - PURPOSE AND METHODS: The outcomes of lung cancer patients who were asymptomatic
      at diagnosis have never been reported as part of a large-scale study. A national
      survey of lung cancer in South Korea registered a total of 8788 patients
      diagnosed in 2005. We report the results herein, with an emphasis on the
      prognosis of the asymptomatic lung cancer patients. RESULTS: Adenocarcinoma was
      the most frequent (36.1%) histopathologic type, followed by squamous cell
      carcinoma (32.1%), large cell carcinoma (1.5%), and small cell carcinoma (13.5%).
      In most cases, lung cancer was detected with subjective symptoms, but 6.5% of
      cases had no symptoms indicative of lung cancer at the time of diagnosis.
      Compared to symptomatic patients, asymptomatic patients were younger, more often
      female, non-smokers, and more frequently presented with adenocarcinoma. Initial
      treatments were surgery (22.1%), radiation therapy (7.8%), chemo-radiation
      therapy (5.4%), and chemotherapy (38%), while 26.6% of patients were recorded to
      have supportive care only. Asymptomatic patients received surgery in 60.0% of
      cases, and they showed significantly longer survival times than symptomatic
      patients. Absence of symptoms at diagnosis significantly reduced the risk of
      death from non-small cell lung cancer, regardless of patient age, patient gender,
      stage at diagnosis, smoking history, or whether treatment was performed, but did
      not reduce the risk of death from small cell lung cancer. CONCLUSIONS:
      Adenocarcinoma has grown to be the leading histopathologic type of lung cancer in
      South Korea. Absence of symptom at diagnosis is a favorable prognostic factor for
      patients with non-small cell lung cancer.

PMID- 18809226
TI  - Third generation triplet cytotoxic chemotherapy in advanced non-small cell lung
      cancer: a systematic overview.
AB  - BACKGROUND: Previous meta-analysis on three drugs combination for treatment of
      advanced non-small cell lung cancer (NSCLC) did not demonstrate an improvement in
      survival, however many of the trials included in this meta-analysis used older
      and less effective cytotoxic drugs. We conducted this analysis to compare the
      relative efficacy of third generation triplet therapy with that of standard
      double therapy in the treatment of advanced NSCLC. METHODS: A MEDLINE search was
      performed using the search terms "lung cancer" and "randomized trials". Trials
      not utilizing a third generation cytotoxic chemotherapeutic agent (paclitaxel,
      docetaxel, vinorelbine, gemcitabine) were excluded. Pooled odds ratios (OR) for
      the objective response and toxicity rates were calculated using the Mantel
      Haenszel estimate. Pooled median ratios for median survival were calculated using
      the weighted sum of the log-ratio of median ratios of individual study. RESULTS:
      We analyzed six randomized comparative trials involving 1932 patients. Patients
      receiving triplet therapy had a significantly higher response rate (OR: 1.33; 95%
      CI, 1.50-2.23; P<0.001). Incidence of grade III/IV hematological toxicity was
      higher with triplet therapy. Non-hematological toxicities, with the exception of
      neuropathy, were similar. Median survival of triplet therapy was not
      significantly different from doublet (MR: 1.10; 95% CI: 0.91-1.35; P=0.059).
      CONCLUSIONS: Triplet therapy with third generation cytotoxic drugs is associated
      with higher tumor response rate at the expense of increased toxicity. Although
      triplet therapy had a better overall survival compared to doublet therapy, this
      did not reach statistical significance.

PMID- 18809227
TI  - Evidence that volume of anterior medial temporal lobe is reduced in seniors
      destined for mild cognitive impairment.
AB  - The present study sought to determine if volumes of specific brain structures
      could discriminate cognitively normal seniors destined to develop mild cognitive
      impairment (MCI) within a few years from those who will remain normal. Brain
      scans were collected from seventy-one cognitively normal seniors. Seventeen
      individuals later developed MCI (the presymptomatic MCI; pMCI group), while fifty
      four remained normal. Whole brain volume (WBV) and volumes of the entorhinal
      cortex (ERC), hippocampus, and three subregions of the hippocampus (head; HH,
      body; HB and tail; HT) were compared. Results indicated that the pMCI group had
      smaller volumes than the normal group in the ERC, HH and HB, but not the HT or
      WBV. When HH/HB volumes and baseline memory test scores were included in a single
      logistic regression model, classification accuracy was very high (area under the
      curve=0.93). These results show that smaller normalized volumes of anterior
      medial temporal lobe structures contribute to the development of MCI, a finding
      which may have implications for identifying seniors at risk for cognitive
      decline.

PMID- 18809229
TI  - 2-Acylhydrazino-5-arylpyrrole derivatives: synthesis and antifungal activity
      evaluation.
AB  - The synthesis and antifungal activity of 2-acylhydrazino-5-arylpyrroles 21-62 are
      described. Pyrrole derivatives 21-62 were evaluated for their antifungal activity
      towards Candida albicans ATCC 10231 and three Candida non-albicans isolated from
      clinical specimens. Most of them showed very good antifungal activities against
      Candidae, having MIC values in the 0.39-3.12 microg/mL range and enhanced
      inhibition potency as compared to that of fluconazole. In addition, some of the
      most active compounds were tested for cytotoxic activities against breast (MCF
      7), lung (H-460), and central nervous system (SF-268) human cancer cell lines
      with the NCI anticancer drug screen. The activity of pyrroles described in this
      paper, along with the low toxicity, shows promise for the future development of
      non-toxic new antimycotic agents. The relationship between functional group
      variation and biological activity of the evaluated compounds is also discussed.

PMID- 18809228
TI  - Rate of entorhinal and hippocampal atrophy in incipient and mild AD: relation to
      memory function.
AB  - In the present study, as part of a more extensive longitudinal investigation of
      the in vivo anatomical markers of early and incipient AD in our laboratory, three
      groups of elderly participants were followed with yearly clinical evaluations and
      high resolution MRI scans over a 6-year period (baseline and 5 years of follow
      up). At baseline, participants consisted of: (1) 35 old subjects with no
      cognitive impairment (controls); (2) 33 participants with amnestic mild cognitive
      impairment (MCI); and (3) 14 patients with very mild AD. 11 participants with
      amnestic MCI received a diagnosis of AD over the follow-up period and 9 controls
      declined in cognitive function. T1 weighted MRI scans were acquired using a 3D
      SPGR pulse sequence. At baseline, both the amnestic MCI and mild AD groups
      differed from the controls in hippocampal and entorhinal cortex volume, but not
      from each other. Longitudinal analyses showed that the rate of atrophy of the
      entorhinal cortex and hippocampus for the stable controls differed significantly
      from MCI participants who converted to AD and the AD groups. Furthermore,
      longitudinal decreases in hippocampal and entorhinal volume were related to
      longitudinal decline in declarative memory performance. These findings suggest
      that the rate of atrophy of mesial temporal lobe structures can differentiate
      healthy from pathological aging.

PMID- 18809230
TI  - An exploration of the attitudes of attenders and non-attenders towards antenatal
      education.
AB  - OBJECTIVE: to explore the attitudes of first-time mothers towards antenatal
      education from the perspective of attenders and non-attenders. DESIGN: a
      qualitative approach was utilised using focus group interviews to collect the
      data. SETTING: the study was conducted in one local health office area of the
      Health Service Executive-South East, Ireland. PARTICIPANTS: a purposive sample of
      first-time mothers was interviewed to explore the area of antenatal education.
      These women included both attenders and non-attenders at antenatal education. KEY
      CONCLUSIONS: the findings suggest there are many strengths, weaknesses,
      opportunities and barriers to antenatal education. Strengths of antenatal
      education included the facilitator of antenatal classes, the information and
      preparation received, and the social aspect of meeting other expectant mothers.
      Barriers to attendance at antenatal education included working night shifts, no
      interest, transport difficulties, inflexible employer, and partner not attending.
      A move away from didactic teaching methods and greater participation and
      involvement of parents was identified as necessary. IMPLICATIONS FOR PRACTICE:
      fundamental issues related to the provision and of antenatal education were
      identified. A need for promotion and advertising of antenatal education was
      identified by the participants. Mothers identified specific needs such as the
      provision of postnatal classes and peer mentoring, flexible availability of
      classes, and facilitators utilising the principles of adult learning to guide
      classes. The mothers alluded to the importance of father's attendance and
      inclusion at classes. In view of the poor uptake of antenatal classes in Ireland,
      it is imperative that an approach to antenatal education is parent centred and
      needs driven.

PMID- 18809231
TI  - FE stress analysis of the interface between the bone and an osseointegrated
      implant for amputees--implications to refine the rehabilitation program.
AB  - BACKGROUND: The direct anchorage of lower-limb prosthesis to the bone has been
      shown to be an excellent alternative for amputees experiencing complications in
      using a conventional prosthetic socket. During rehabilitation phase, amputees are
      asked to apply static loading on the abutment perpendicular to a weigh scale to
      prepare the bone to tolerate the forces likely to be developed during walking.
      The weigh scale measures only the vertical force. A different loading protocol
      can affect the bone-implant interface stresses and the outcome of the
      rehabilitation. METHODS: This study developed a Finite Element model to study the
      stresses in the bone adjacent to the implant. Three loading conditions were
      applied based on the experimentally measured load: (1) vertical force applied
      along the long axis of the limb, corresponding to the load clinically prescribed
      in the weight bearing exercise; (2) loads applied on the three axes,
      corresponding to the "true" load measured simultaneously by a tri-axial load
      transducer during the same exercise; and (3) loads experienced during independent
      walking. FINDINGS: The model revealed that the weigh scale might in fact be
      applying much higher and less uniform stresses on the bone than expected. During
      walking, high stress occurred at various locations of the implanted region, which
      was different from the patterns of stress distribution during weight bearing
      exercises. INTERPRETATIONS: The difference in stress among three loading
      conditions implies that tri-axial load should be monitored during the weight
      bearing exercises and carefully prescribed.

PMID- 18809232
TI  - Effects of abdominal belts on the cross-sectional shape of the trunk during
      intense contraction of the trunk muscles observed by computer tomography.
AB  - BACKGROUND: Several mechanisms of how abdominal belts affect the trunk have been
      postulated, but very little is known about how the belts affect the cross
      sectional shape of the trunk during trunk muscle exertions. METHODS: To evaluate
      the effects of abdominal belts on the cross-sectional shape of the trunk during
      contraction of the trunk muscles, CT images at the third lumbar vertebra level of
      20 healthy males (age: 23-45 years) under 8 different conditions (combinations of
      performing or not performing the Valsalva maneuver after full inhalation or at
      neutral respiratory state, while wearing or not wearing a 100-mm-wide abdominal
      belt) were evaluated. The cross-sectional shapes of the trunk seen on CT images
      taken at the level of the 3rd lumbar vertebra were compared using three-way
      ANOVA. FINDINGS: Wearing the belt decreased the cross-sectional area of the
      trunk, and wearing it while performing the Valsalva maneuver and during
      inhalation compressed the postero-lateral part of the trunk and made the trunk
      nearly round by increasing the ratio of the anterior-posterior width to the right
      left width. INTERPRETATION: A wide belt cinched around the abdomen exerts
      external hoop tension on the trunk and stiffens the trunk. When the belt is worn
      during the Valsalva maneuver after deep inhalation, the posterolateral portion of
      the trunk is compressed and the trunk becomes circular.

PMID- 18809233
TI  - The role of the right posterior parietal cortex in temporal order judgment.
AB  - Perceived order of two consecutive stimuli may not correspond to the order of
      their physical onsets. Such a disagreement presumably results from a difference
      in the speed of stimulus processing toward central decision mechanisms. Since
      previous evidence suggests that the right posterior parietal cortex (PPC) plays a
      role in modulating the processing speed of a visual target, we applied single
      pulse TMS over the region in 14 normal subjects, while they judged the temporal
      order of two consecutive visual stimuli. Stimulus-onset-asynchrony (SOA) randomly
      varied between -100 and 100 ms in 20-ms steps (with a positive SOA when a target
      appeared on the right hemi-field before the other on the left), and a point of
      subjective simultaneity was measured for individual subjects. TMS stimulation was
      time-locked at 50, 100, 150, and 200 ms after the onset of the first stimulus,
      and results in trials with TMS on right PPC were compared with those in trials
      without TMS. TMS over the right PPC delayed the detection of a visual target in
      the contralateral, i.e., left hemi-field by 24 (+/-7 SE) ms and 16 (+/-4 SE) ms,
      when the stimulation was given at 50 and 100 ms after the first target onset. In
      contrast, TMS on the left PPC was not effective. These results show that the
      right PPC is important in a timely detection of a target appearing on the left
      visual field, especially in competition with another target simultaneously
      appearing in the opposite field.

PMID- 18809235
TI  - External artifacts by advanced life support providers misleading automated
      external defibrillators.
AB  - BACKGROUND: The ECG analysis algorithm of automated external defibrillators
      (AEDs) shows reduced sensitivity and specificity in the presence of external
      artifacts. Therefore, ECG analyses are preceded by voice prompts. We investigated
      if advanced life support (ALS) providers follow these prompts, and the
      consequences if they do not. METHODS: In a two-tiered EMS system all 510 ECG
      analyses from 135 resuscitation attempts with a Laerdal FR2 AED (applied by
      emergency medical technicians [EMTs] and subsequently used by ALS providers) were
      prospectively evaluated. The ALS data were compared with data before arrival of
      ALS providers (EMT data) using Mc Nemar test. RESULTS: In the presence of ALS
      providers, 286 ECG rhythm analyses were performed. In the 96 analyses with
      shockable rhythms, artifacts were detected in 35 (36%), leading to a wrongful no
      shock decision in 19 (20%). Corresponding EMT data were 67 analyses with
      shockable rhythms, with artifacts in 18 (27%; p<0.001) but a wrongful no shock
      decision in only 3 (4%; p<0.001). ALS providers also failed to deliver the AED
      shock in 7 of the 77 analyses with an appropriate shock decision (9%). This was
      never found in the EMT data. In the 190 analyses of a non-shockable rhythm in the
      presence of ALS providers, artifacts were detected in 120 (63%) leading to one
      spurious shock (0.5%). Corresponding EMT data were 157 analyses, with artifacts
      in 87 (55%; p=0.20) but no spurious shocks. CONCLUSIONS: External artifacts were
      frequently found, sometimes leading to important errors. Consequently, more
      training is needed, especially for ALS providers.

PMID- 18809234
TI  - Superior temporal activation in response to dynamic audio-visual emotional cues.
AB  - Perception of emotion is critical for successful social interaction, yet the
      neural mechanisms underlying the perception of dynamic, audio-visual emotional
      cues are poorly understood. Evidence from language and sensory paradigms suggests
      that the superior temporal sulcus and gyrus (STS/STG) play a key role in the
      integration of auditory and visual cues. Emotion perception research has focused
      on static facial cues; however, dynamic audio-visual (AV) cues mimic real-world
      social cues more accurately than static and/or unimodal stimuli. Novel dynamic AV
      stimuli were presented using a block design in two fMRI studies, comparing
      bimodal stimuli to unimodal conditions, and emotional to neutral stimuli. Results
      suggest that the bilateral superior temporal region plays distinct roles in the
      perception of emotion and in the integration of auditory and visual cues. Given
      the greater ecological validity of the stimuli developed for this study, this
      paradigm may be helpful in elucidating the deficits in emotion perception
      experienced by clinical populations.

PMID- 18809236
TI  - Induction of therapeutic hypothermia during prehospital CPR using ice-cold
      intravenous fluid.
AB  - AIM OF THE STUDY: Primarily, to investigate induction of therapeutic hypothermia
      during prehospital cardiopulmonary resuscitation (CPR) using ice-cold intravenous
      fluids. Effects on return of spontaneous circulation (ROSC), rate of rearrest,
      temperature and haemodynamics were assessed. Additionally, the outcome was
      followed until discharge from hospital. MATERIALS AND METHODS: Seventeen adult
      prehospital patients without obvious external causes for cardiac arrest were
      included. During CPR and after ROSC, paramedics infused +4 degrees C Ringer's
      acetate aiming at a target temperature of 33 degrees C. RESULTS: ROSC was
      achieved in 13 patients, 11 of whom were admitted to hospital. Their mean initial
      nasopharyngeal temperature was 35.17+/-0.57 degrees C (95% CI), and their
      temperature on hospital admission was 33.83+/-0.77 degrees C (-1.34 degrees C,
      p<0.001). The mean infused volume of cold fluid was 1571+/-517 ml. The rate of
      rearrest after ROSC was not increased compared to previous reports. Hypotension
      was observed in five patients. Of the 17 patients, 1 survived to hospital
      discharge. CONCLUSION: Induction of therapeutic hypothermia during prehospital
      CPR and after ROSC using ice-cold Ringer's solution effectively decreased
      nasopharyngeal temperature. The treatment was easily carried out and well
      tolerated.

PMID- 18809237
TI  - FcgammaRII mediates platelet aggregation caused by disintegrins and GPIIb/IIIa
      monoclonal antibody, AP2.
AB  - OBJECTIVE: Disintegrins, snake venom-derived Arg-Gly-Asp (RGD)-containing
      polypeptides, and GPIIb/IIIa antagonist (AP2) block fibrinogen binding to
      GPIIb/IIIa of activated platelets, however, the combination of these two agents
      caused platelet aggregation. We hypothesize that disintegrin initially binds to
      specific epitope of GPIIb/IIIa, causing conformational change, and the
      recruitment of FcgammaRII, which can be bound by AP2, and finally triggering
      platelet aggregation. MATERIALS AND METHODS: We prepared human platelet
      suspensions and measured platelet aggregation, Ca2+ mobilization, thromboxane B2
      formation, and signal transduction. RESULTS: Disintegrin (e.g., accutin) and AP2
      (a monoclonal antibody [mAb]-raised against GPIIb/IIIa) individually inhibited
      human platelet aggregation caused by collagen. However, as both accutin and AP2
      were sequentially added into platelet suspension, platelet aggregation occurred.
      Accutin/AP2 caused shape change, cytosolic Ca2+ mobilization, P-selectin
      expression, and thromboxane A2 formation. Tirofiban, FcgammaRII mAb, or
      indomethacin completely inhibited platelet aggregation caused by accutin/AP2.
      Accutin/AP2 also caused tyrosine phosphorylation of signal molecules.
      Disintegrins enhanced AP2 binding to platelets, and AP2 also promoted disintegrin
      binding to platelets. FcgammaRII mAb inhibited the enhanced fluorescein
      isothiocyanate-disintegrin binding to platelet caused by AP2. Immunoprecipitation
      of the lysates of disintegrin/AP2-treated platelets using FcgammaRII Ab showed
      complex formation of GPIIb/IIIa and FcgammaRII. CONCLUSION: FcgammaRII mediates
      platelet aggregation caused by disintegrin and AP2, triggering a phospholipase C,
      phospholipase A2, Src-, Syk kinases, and Ca2+-dependent activation process. AP2
      triggers platelet aggregation via binding to accessible FcgammaRII and the
      conformation-altered GPIIb/IIIa caused by disintegrin.

PMID- 18809238
TI  - Costimulation molecule expression and subset distribution of blood dendritic
      cells in normal children and newly diagnosed pediatric leukemia and lymphoma
      patients.
AB  - OBJECTIVE: To characterize dendritic cell (DC) numbers, subset distribution,
      phenotype, and costimulation molecule expression in a normal pediatric population
      and in a lymphoblastic malignant pretherapy pediatric population. DC are potent
      antigen-presenting cells and are crucial for initiating specific immune
      responses. MATERIALS AND METHODS: We first analyzed peripheral blood samples of
      healthy pediatric controls (n=72). Once a range of normal parameters was
      established, we compared these to newly diagnosed pediatric leukemia and lymphoma
      patients prior to receiving therapy (n=69). Using flow cytometry, we examined
      blood DC cell-surface expression of CD80, CD86, CD40, CD18, CD50, CD83, CD123,
      CD58, CD54, and CD11c. RESULTS: Expression of each of these molecules was
      significantly altered except for CD80, CD83, and CD58. When compared to healthy
      children, absolute blood DC were reduced in children with leukemia or
      lymphoblastic lymphoma (p<0.0001) and children with Hodgkin's disease (p=0.0028).
      Additionally, lymphocyte function in vitro, was impaired (p=0.0489) for children
      with lymphoblastic malignancies, while patients with Hodgkin's disease had normal
      proliferative function. CONCLUSIONS: Our results show that peripheral blood DC
      from children with newly diagnosed leukemia or lymphoma are significantly altered
      in number, subset distribution, and costimulation molecule expression, and that
      lymphocyte function is impaired compared to healthy pediatric controls.

PMID- 18809239
TI  - Modulation of redox pathways in neutrophils from sickle cell disease patients.
AB  - OBJECTIVE: Interaction of nitric oxide (NO) with enzymatic sources of reactive
      species exerts modulatory actions on inflammatory signaling mechanisms. MATERIALS
      AND METHODS: NADPH oxidase, total peroxidase, cyclooxygenase (COX) activity, and
      NO consumption were measured in neutrophils isolated from sickle cell disease
      (SCD) patients and healthy controls. Glutathione (GSH) levels and expression of
      inducible NO synthase (NOS-2) were also analyzed to assess intracellular redox
      state and NO production, respectively. RESULTS: Functional assay of NADPH oxidase
      was performed by measuring superoxide release, which was similar in control and
      SCD, both at basal conditions and in response to N-formyl-methionyl-leucyl
      phenylalanine stimulation. Peroxidase activity, assessed spectrophotometrically,
      was not significantly different in SCD neutrophils compared to controls. Total
      COX activity, measured via an assay kit, was significantly increased in SCD
      neutrophils. The increase in total COX activity observed in SCD was due to
      enhanced activity of COX-2, differentiated by using the isoform-specific
      inhibitors DuP-697 and SC-560. Western blot analysis of COX-2 protein in SCD and
      control neutrophils confirmed increased enzyme activity in the diseased group.
      Western blot analysis of neutrophil lysates from SCD patients showed
      significantly increased NOS-2 protein content, compared to controls.
      Spectrophotometric measurement of GSH and nitrate/nitrite levels showed a
      decrease in GSH and an increase in nitrate/nitrite content in SCD neutrophils.
      Electrochemical measurement of NO consumption both under basal conditions and
      after N-formyl-methionyl-leucyl-phenylalanine stimulation revealed a significant
      decrease in SCD neutrophils compared to controls. CONCLUSIONS: Depletion of GSH
      in SCD neutrophils may impact on rates of NO consumption and reflects increased
      oxidative stress associated with neutrophil activation.

PMID- 18809240
TI  - Mesodermal patterning activity of SCL.
AB  - The transcription factor SCL is critically required for establishing
      hematopoiesis and for proper endothelial development, but not for maintenance of
      hematopoietic stem cells or endothelial cells in the adult. Conflicting data
      exists regarding the developmental function of SCL, namely, whether it acts as a
      master regulator, actively patterning mesoderm toward hematopoietic development
      at the expense of other lineages, or is merely necessary to maintain the earliest
      committed hematopoietic precursors. To answer this question, we have engineered
      murine embryonic stem cells with a conditional doxycycline-inducible SCL
      transgene, and evaluated the effects of SCL expression at defined time points
      during in vitro development. Continual SCL expression during differentiation
      results in markedly increased hematopoiesis. By using pulses of gene expression
      over a 6-day differentiation time course, we map and characterize windows of SCL
      responsiveness. Notably, a pulse of SCL expression during early mesodermal
      patterning (48 to 72 hours of differentiation) promoted Flk1+ PDGFRalphaneg
      presumptive extraembryonic/lateral plate mesoderm at the expense of PDGFRalpha+
      Flk1neg presumptive paraxial mesoderm. Consistent with this, the early pulse of
      SCL expression also expanded hematopoietic colony-forming cell numbers, while
      concomitantly repressing expression of paraxial and cardiac markers, and
      inhibited development of beating cardiomyocytes. By mixing the inducible
      embryonic stem cells with fluorescently labeled wild-type cells in chimeric
      embryoid bodies, we show that these effects of SCL are cell autonomous. These
      data support a master-regulatory role for SCL in mesodermal patterning, in
      addition to its established later roles in hematopoietic differentiation.

PMID- 18809241
TI  - Prevention of acute graft-vs-host disease by a single low-dose cyclophosphamide
      injection following allogeneic bone marrow transplantation.
AB  - OBJECTIVE: Previously, we documented that conditioning based on donor-specific
      cell transfusion (DST) and subsequent selective depletion of activated donor
      reactive cells by cyclophosphamide (CY) facilitates alloengraftment in a murine
      transplantation model. Transplantation event represents a strong immunogenic
      stimulus for host-reactive donor T cells that induce graft-vs-host disease
      (GVHD). Therefore, in this study, we addressed the question of whether a single
      posttransplantation CY administration (CY2) can prevent acute GVHD-related
      mortality without compromising engraftment of allogeneic transplant. MATERIALS
      AND METHODS: Splenocyte-enriched C57BL/6 bone marrow was transplanted to BALB/c
      recipients after mild irradiation, and conditioning with DST and 100 mg/kg CY.
      Following transplantation, recipients were left untreated or given on a specified
      day a single CY2 injection (50 mg/kg). All animals were monitored for survival,
      chimerism, and clinical signs of GVHD. Experimental mice that received BCL1
      leukemia cells before transplantation were monitored for leukemia-related
      mortality as well. RESULTS: Animals that received no CY2 after transplantation
      died of acute GVHD. A single low-dose CY2 treatment within the first 5 days after
      transplantation prevented mortality in most recipients. However, only CY2
      administration on days +1 or +5 preserved chimerism. Most chimeras survived GVHD
      free for >200 days. Prolonged persistence of host-reactive T cells in mice (CY2
      on day +5) permitted a reduction to be made in engraftment-essential irradiation
      dose and preserved a strong graft-vs-leukemia effect of transplantation.
      CONCLUSION: Acute GVHD can be prevented in mice by a single properly timed
      posttransplantation low-dose CY administration.

PMID- 18809242
TI  - From land cover change to land function dynamics: a major challenge to improve
      land characterization.
AB  - Land cover change has always had a central role in land change science. This
      central role is largely the result of the possibilities to map and characterize
      land cover based on observations and remote sensing. This paper argues that more
      attention should be given to land use and land functions and linkages between
      these. Consideration of land functions that provide a wide range of goods and
      services makes more integrated assessments of land change possible. The
      increasing attention to multifunctional land use is another incentive to develop
      methods to assess changes in land functions. A number of methods to quantify and
      map the spatial extent of land use and land functions are discussed and the
      implications for modeling are identified based on recent model approaches in land
      change science. The mixed use of land cover, land use and land function in maps
      and models leads to inconsistencies in land change assessments. Explicit
      attention to the non-linear relations between land cover, land use and land
      function is essential to consistently address land change. New methods to map and
      quantify land function dynamics will enhance our ability to understand and model
      land system change and adequately inform policies and planning.

PMID- 18809243
TI  - MYC pathway is activated in clear cell renal cell carcinoma and essential for
      proliferation of clear cell renal cell carcinoma cells.
AB  - Clear cell renal cell carcinoma (ccRCC) is the major and aggressive subtype of
      RCC. Previously, we identified 383 differentially expressed genes by analyzing
      full-length cDNA libraries of ccRCC and normal kidney tissues. In this study, we
      applied functional network analysis to the differentially expressed genes for
      identifying deregulated molecular pathways in ccRCC, and the results indicated
      that MYC showed a prominent role in the highest scoring network. The upregulation
      of MYC expression was validated in ccRCC tissues and cell lines. Furthermore,
      Knockdown of MYC expression by MYC-specific siRNA significantly inhibited the
      abilities of uncontrolled proliferation, anchorage-independent growth and
      arrested cell cycle in the G0/G1 phase in ccRCC cells. Moreover, we found that 37
      differentially expressed genes were shown to be MYC-target genes, and the
      upregulation of the MYC-target genes BCL2, CCND1, PCNA, PGK1, and VEGFA were
      demonstrated. The expression of these MYC-target genes was significantly
      correlated with the expression of MYC in ccRCC tissues, and knockdown of MYC also
      suppressed the expression of these MYC-target genes in ccRCC cells. The
      recruitment of MYC to the promoter regions of BCL2, CCND1, PCNA, PGK1, and VEGFA
      was shown by Chromatin immunoprecipitation assay. These results suggest that MYC
      pathway is activated and plays an essential role in the proliferation of ccRCC
      cells.

PMID- 18809244
TI  - Combination of imatinib and vinorelbine enhances cell growth inhibition in breast
      cancer cells via PDGFR beta signalling.
AB  - INTRODUCTION: Imatinib mesylate is a tyrosine kinase receptor inhibitor targeted
      against PDGFR alpha and beta, c-kit and bcr-abl. These receptors regulate
      cellular processes such as proliferation, differentiation, and survival. This
      study was performed to evaluate the effects of imatinib on breast cancer cell
      lines with respect to the activity of PDGFR beta and Akt: a downstream modulator
      of cell growth and survival. METHODS: Expression of imatinib targets was analyzed
      with reverse transciptase PCR and immunoblotting assays in the breast cell lines
      MDA MB 231, MCF 7, ZR 75-1, and T 47-D. Changes on receptor expression and
      phosphorylation status under imatinib were evaluated using drug concentrations of
      2 to 10 microM. The anti-proliferative and pro-apoptotic effects of imatinib
      alone and in combination with vinorelbine were investigated with an MTT and TUNEL
      assay. RESULTS: Imatinib inhibited growth and induced apoptosis of all cell lines
      examined. This effect was increased when combined with vinorelbine. A dose
      dependent inhibitory effect on the phosphorylation of PDGFR beta and Akt was
      detected. CONCLUSIONS: The growth inhibitory effect of imatinib on breast cell
      lines may be caused by inhibiting the activity of the tyrosine kinases PDGFR beta
      and Akt. Imatinib is a promising novel drug for targeted therapy of breast cancer
      patients.

PMID- 18809246
TI  - Colorectal cancer cell detection by 5-aminolaevulinic acid-loaded chitosan nano
      particles.
AB  - Colorectal cancer is one of the leading causes of malignant death in Taiwan
      because it often remains undetected until later stages of the disease. In this
      study, we designed an oral form nano-particle to encapsulate 5-aminolaevulinic
      acid (5-ALA) to improve the detection of colorectal cancer cells in vivo. The
      nano-particle should escape from bacteria uptake in the gastrointestinal tract
      which seriously interferes the results of endoscopic observation. In this study,
      chitosan was mixed with sodium tripolyphosphate (STPP) and 5-ALA to prepare
      chitosan nano-particles (CN) and 5-ALA loaded chitosan nano-particles (CNA) by
      adding different pH values and concentrations of 5-ALA solution. The average
      particle size and zeta-potential of CN and CNA were measured by the Zetasizer
      3000. The results revealed that particle size with different zeta-potential could
      be manipulated just by 5-ALA concentrations and pH values. CNA particles prepared
      at pH 7.4 and pH 9 of 5-ALA solutions with a concentration higher than 0.5 mg/ml
      showed a promising loading efficiency of up to 75% and an optimum average
      particle size of 100 nm. The zeta-potential for CNA was over 30 mV that kept the
      nano-particle stable without aggregation when stored in suspension solution.
      Fluorescence microscope examination showed that CNA could be engulfed by Caco-2
      colon cancer cells but showed no evidence of being taken up by Escherichia coli.
      This result implies that CNA could exclude the influence of normal flora inside
      the gut and serves as an adequate tool for fluorescent endoscopic detection of
      colorectal cancer cells in vivo.

PMID- 18809245
TI  - Cancer stem cells in multiple myeloma.
AB  - Several key observations providing evidence for the cancer stem cell hypothesis
      and insights into the unique biology of these cells have come from the study of
      multiple myeloma. These include evidence that cancer cells may be functionally
      heterogeneous in spite of their genetic homogeneity and that malignant
      progenitors share many biological features with normal adult stem cells including
      drug resistance and regulatory processes governing self-renewal. We review
      studies that have examined clonogenic cells in multiple myeloma, highlight
      controversies regarding the cell of origin in multiple myeloma, and discuss
      potential targeting strategies.

PMID- 18809247
TI  - Vat dye sorption onto crude dehydrated sewage sludge.
AB  - In this work, sewage sludge is used as a textile dye adsorbent. A sample of crude
      dehydrated sewage sludge issued from an urban wastewater treatment plant (high
      rate aeration, activated sludge process, Sahline, Tunisia) is utilized for vat
      dye retention. The main objective of this work is to evaluate the "efficiency" of
      the crude material on vat dye sorption. However, no treatment to modify any of
      the adsorbent properties was considered. Although the relatively low specific
      surface area (about 3.2m(2)g(-1)) compared to more conventional adsorbents, the
      used material shows very interesting retention capacities when used with water
      pollutants. The pseudo, first and second order kinetic models have been used to
      investigate the retention mechanism. When linearized, the pseudo-second order
      fit, for the both used dyes, in a better way the obtained experimental results
      than the pseudo-first order kinetic model. For equilibrium dye uptake amount it
      is found that the used material has a capacity (Langmuir Freundlich monolayer) of
      73.1mg/g to fix the VAT RED 10 and 58.7 mg/g to fix the VAT ORANGE 11.

PMID- 18809248
TI  - Characterization of solids originating from the Fenton's process.
AB  - Fenton's process has proven to be a viable alternative for the oxidation of
      organic pollutants in mixed waste chemicals, with a high efficiency in the
      removal of heavy metals from the effluent as a side effect. However, a solid
      residue loaded with metals is obtained as a by-product. In this paper, the solids
      originating from the Fenton's oxidation of mixed waste chemicals from an academic
      laboratory were studied. The process was applied to different wastewater cases
      (two composite samples generated in different periods) in order to study the
      effect of their characteristics on the residues composition. Residues were
      evaluated and classified according to their leaching properties. In addition, a
      most comprehensive assessment of metal mobility in the residues was obtained by
      chemical speciation. The Fenton's residues were classified as hazardous according
      to Brazilian waste regulations. The application of the sequential dissolution
      procedure indicated that the metals in the Fenton's residues are mainly
      constituted of amorphous material (over 80%). Furthermore, the reactive fractions
      of the residues (exchangeable and amorphous iron oxide fractions) retain most of
      remaining metals. Therefore, the Fenton's residues present great potential for
      environmental contamination, and require an administration system and control of
      their final disposal.

PMID- 18809249
TI  - On-line monitoring of remediation process of chromium polluted soil using LIBS.
AB  - Due to large growth in leather and textile industries to cater for the needs of a
      growing world population, contamination of soil and water resources by chromium
      has become a great threat for humans and animals. In this work, Laser Induced
      Breakdown Spectroscopy (LIBS) was applied to monitor the remediation process of
      soil contaminated with Chromium metal. This study was conducted at a laboratory
      scale by setting up an experiment in a container holding soil contaminated with
      chromium. This setup represents actual field conditions where remediation process
      could be applied and monitored for the removal of toxic metals like Cr. For
      generation of LIBS spectrum, the plasma was produced by focusing a pulsed Nd: YAG
      laser at 1064 nm on the soil contaminated with chromium under remediation
      process. The evaluation of the potential and capabilities of LIBS as a rapid tool
      for remediation process of contaminated sites is discussed in detail. Optimal
      experimental conditions were evaluated for improving the sensitivity of our LIBS
      system for monitoring of remediation process through parametric dependence study.
      The minimum detection limit of our spectrometer for chromium in soil matrix was 2
      mg Kg(-1).

PMID- 18809250
TI  - Studies on biosorption equilibrium and kinetics of Cd2+ by Streptomyces sp. K33
      and HL-12.
AB  - The sorption of Cd(2+) by Streptomyces sp. K33 and HL-12 was investigated. The
      removal efficiency increased with pH, but no obvious differences with different
      temperatures. Fourier transform infrared (FT-IR) was used to characterize the
      interaction between Cd(2+) and K33 and HL-12. Results revealed that the presence
      of amino, carboxyl, hydroxyl and carbonyl groups were responsible for the
      biosorption of Cd(2+). Strain HL-12 had more changes in the functional groups
      than K33. Biosorption equilibrium was established earlier by strain K33 than that
      by HL-12, and K33 had higher adsorption ratio. Langmuir, Freundlich and Dubinin
      Radushkevich (D-R) isotherms were used to describe the adsorption experiment,
      Langmuir model fitted the experiment data best. Strain K33 showed greater
      sorption capacities with 38.49 mg Cd(2+)/g dry cells. Pseudo-first-order and
      second-order kinetic models were used to describe the kinetic data, and second
      order kinetic model fitted better. About 70% recovery of Cd(2+) could be obtained
      at pH <or= 3 from metal-loaded biomass of strains HL-12 and K33.

PMID- 18809251
TI  - Heavy metal contamination of river Yamuna, Haryana, India: Assessment by Metal
      Enrichment Factor of the Sediments.
AB  - Concentration of Heavy Metals (Cd, Cr, Fe, Ni) in water, plants and sediments of
      river Yamuna flowing in Haryana through Delhi are reported here selecting 14
      stations covering the upstream and downstream sites of major industrial complexes
      of the State. Some important characteristics of river water and sediments (pH,
      EC, Cl(-), SO(3)(2-), and PO(4)(3-) in water and sediments, COD of water and
      organic matter content of sediments) were also analysed and inter-relationships
      of all these parameters with heavy metal concentration in different compartments
      were examined. The sediments of the river show significant enrichment with Cd and
      Ni indicating inputs from industrial sources. Concentrations of Cr are moderate
      and show high enrichment values only at a few sites. Enrichment factor for Fe is
      found to be <1, showing insignificant effect of anthropogenic flux.
      Concentrations of these metals in river water are generally high exceeding the
      standard maximum permissible limits prescribed for drinking water, particularly
      in the downstream sites. The aquatic plants show maximum accumulation of Fe. The
      other heavy metals Cd, Cr and Ni, though less in concentration, show some
      accumulation in the plants growing in contaminated sites. Interrelationships of
      metal concentration with important characteristics of water and sediment have
      been analysed. Analysis of heavy metals in water, sediments and littoral flora in
      the stretch of river Yamuna is first study of itself and interrelationship of
      metal concentration and other important characteristics make the study
      significant and interesting in analysing the pollution load at different points
      of the river body.

PMID- 18809252
TI  - Application of visible-light photocatalysis with nitrogen-doped or unmodified
      titanium dioxide for control of indoor-level volatile organic compounds.
AB  - The present study evaluated visible-light photocatalysis, applying an annular
      reactor coated with unmodified or nitrogen (N)-doped titanium dioxide (TiO(2)),
      to cleanse gaseous volatile organic compounds (VOCs) at indoor levels. The
      surface chemistry investigation of N-doped TiO(2) suggested that there was no
      significant residual of sulfate ions or urea species on the surface of the N
      doped TiO(2). Under visible-light irradiation, the photocatalytic technique using
      N-doped TiO(2) was much superior to that for unmodified TiO(2) for the
      degradation of VOCs. Moreover, the degradation efficiency by a reactor coated
      with N-doped TiO(2) was well above 90% for four target compounds (ethyl benzene,
      o,m,p-xylenes), suggesting that this photocatalytic system can be effectively
      employed to cleanse these pollutants at indoor air quality (IAQ) levels. The
      degradation efficiency of all target compounds increased as the stream flow rate
      (SFR) decreased. For most target compounds, a reactor with a lower hydraulic
      diameter (HD) exhibited elevated degradation efficiency. The result on humidity
      effect suggested that the N-doped photocatalyst could be employed effectively to
      remove four target compounds (ethyl benzene, o,m,p-xylenes) under conditions of
      less humidified environments, including a typical indoor comfort range (50-60%).
      Consequently, it is suggested that with appropriate photocatalytic conditions, a
      visible-light-assisted N-doped photocatalytic system is clearly an important tool
      for improving IAQ.

PMID- 18809253
TI  - Re: Inherent safety, ethics and human error.

PMID- 18809254
TI  - Characterization of TiO(2)-chitosan/glass photocatalyst for the removal of a
      monoazo dye via photodegradation-adsorption process.
AB  - In this paper, the newly explored TiO(2)-Chitosan/Glass was suggested as a
      promising alternative material to conventional means of wastewater treatment.
      Characterization of TiO(2)-Chitosan/Glass photocatalyst was studied with SEM-EDX,
      XRD, and Fourier transform infrared spectroscopy (FTIR) analysis. The combination
      effect of photodegradation-adsorption process for the removal of methyl orange
      (MO), an acid dye of the monoazo series occur promisingly when four layers of
      TiO(2)-Chitosan/Glass photocatalyst was used for MO removal. Approximately, 87.0%
      of total MO removal was achieved. The reactive -NH(2), -OH, and metal oxide
      contents in the prepared photocatalyst responsible for the photodegradation
      adsorption effect were confirmed by FTIR study. Similarly, MO removal behavior
      was well supported by SEM-EDX and XRD analysis. Significant dependence of MO
      removal on the TiO(2)-Chitosan loading can be explained in terms of relationship
      between quantum yield of photocatalytic reactions and photocatalyst
      structure/activity. Hence, the research work done thus far suggests a new method,
      having both the advantages of photodegradation-adsorption process in the
      abatement of various wastewater pollutants.

PMID- 18809255
TI  - Adsorption of methylene blue onto hazelnut shell: Kinetics, mechanism and
      activation parameters.
AB  - The adsorption kinetics of methylene blue (MB) on the hazelnut shell with respect
      to the initial dye concentration, pH, ionic strength, particle size and
      temperature were investigated. The rate and the transport/kinetic processes of MB
      adsorption were described by applying the first-order Lagergren, the pseudo
      second-order, mass transfer coefficient and the intraparticle diffusion models.
      Kinetic studies showed that the kinetic data were well described by the pseudo
      second-order kinetic model. Significant increases in initial adsorption rate were
      observed with the increase in temperature followed by pH and initial MB
      concentration. The intraparticle diffusion was found to be the rate-limiting step
      in the adsorption process. Adsorption activation energy was calculated to be
      45.6kJmol(-1). The values of activation parameters such as free energy
      (DeltaG(*)), enthalpy (DeltaH(*)) and entropy (DeltaS(*)) were also determined as
      83.4kJmol(-1), 42.9kJmol(-1) and -133.5Jmol(-1)K(-1), respectively.

PMID- 18809256
TI  - Removal of tartrazine from aqueous solutions by strongly basic polystyrene anion
      exchange resins.
AB  - The removal of tartrazine from aqueous solutions onto the strongly basic
      polystyrene anion exchangers of type 1 (Amberlite IRA-900) and type 2 (Amberlite
      IRA-910) was investigated. The experimental data obtained at 100, 200, 300 and
      500 mg/dm(3) initial concentrations at 20 degrees C were applied to the pseudo
      first order, pseudo-second order and Weber-Morris kinetic models. The calculated
      sorption capacities (q(e,cal)) and the rate constant of the first order
      adsorption (k(1)) were determined. The pseudo-second order kinetic constants
      (k(2)) and capacities were calculated from the plots of t/q(t) vs. t, 1/q(t) vs.
      1/t, 1/t vs. 1/q(t) and q(t)/t vs. q(t) for type 1, type 2, type 3 and type 4 of
      the pseudo-second order expression, respectively. The influence of phase contact
      time, solution pH and temperature on tartrazine removal was also discussed. The
      FTIR spectra of pure anion exchangers and those loaded with tartrazine were
      recorded, too.

PMID- 18809257
TI  - Descending facilitation from the brainstem determines behavioural and neuronal
      hypersensitivity following nerve injury and efficacy of pregabalin.
AB  - Various mechanisms at peripheral, spinal and/or supraspinal levels may underlie
      neuropathic pain. The nervous system's capacity for long-term reorganisation and
      chronic pain may result from abnormalities in RVM facilitatory On cells. Hence,
      via brainstem injections of the toxic conjugate dermorphin-saporin, which
      specifically lesions facilitatory cells expressing the mu-opioid receptor (MOR),
      we sought to determine the influence of these cells in normal and spinal nerve
      ligated (SNL) rats. We combined behavioural, electrophysiological and
      pharmacological techniques to show that the supraspinal facilitatory drive is
      essential for neuronal processing of noxious stimuli in normal and neuropathic
      states, and that descending facilitatory neurones maintain behavioural
      hypersensitivities to mechanical stimuli during the late stages of nerve injury.
      Furthermore, we showed that these neurones are essential for the state-dependent
      inhibitory actions of pregabalin (PGB), a drug used in the treatment of
      neuropathic pain. During the early stages of nerve injury, or following medullary
      MOR cell ablation, PGB is ineffective at inhibiting spinal neuronal responses
      possibly due to quiescent spinal 5HT(3) receptors. This can however be overcome,
      and PGB's efficacy restored, by pharmacologically mimicking the descending drive
      at the spinal level with a 5HT(3) receptor agonist. Since RVM facilitatory
      neurones are integral to a spino-bulbo-spinal loop that reaches brain areas co
      ordinating the sensory and affective components of pain, we propose that activity
      therein may influence painful outcome following nerve injury, and responsiveness
      to treatment.

PMID- 18809258
TI  - Toxoplasma gondii and Leptospira spp. infection in free-ranging armadillos.
AB  - Armadillos are primitive mammals used as food, mostly in rural areas. These
      animals may be sources of toxoplasmosis and leptospirosis infection for humans,
      but there is little information about their potential risk as reservoirs. In
      order to determine the prevalence of armadillos infected by Toxoplasma gondii and
      Leptospira spp., serum samples of 31 nine-banded armadillos (Dasypus
      novemcinctus), three six-banded armadillos (Euphractus sexcinctus), two naked
      tailed armadillos (Cabassous tatouay) and two long-nosed armadillos (D.
      hybridus), captured in the mid-west region of the state of Sao Paulo, were
      analyzed for leptospirosis using the Microscopic Agglutination Test (MAT-l), and
      for toxoplasmosis using the Modified Agglutination Test (MAT-t). Only 4/31
      (12.90%) nine-banded armadillos were positive for T. gondii, while 3/31 (9.68%)
      nine-banded armadillos and 1/3 (33.33%) six-banded armadillos presented
      antibodies to Leptospira spp., demonstrating the potential risk of T. gondii and
      Leptospira spp. transmission to humans, mainly due the habit of eating the meat
      of these animals in rural areas.

PMID- 18809260
TI  - Late onset neurodegenerative diseases: a theoretical point of view.

PMID- 18809259
TI  - Neuroticism and introversion are associated with salivary cortisol patterns in
      adolescents.
AB  - Previous studies have yielded equivocal findings on the relationship between
      personality and cortisol activity. The present study examined associations
      between personality and cortisol activity in a large, diverse adolescent sample,
      while partialling the effects of relevant demographic and health-related
      covariates. A subsample of 230 participants (57% of whom reported elevated
      neuroticism) was selected from a larger sample of 16-18-year olds involved in a
      study on risk factors for emotional disorders. Subsample participants completed a
      battery of personality questionnaires, and saliva collection was requested
      several months later on three consecutive days at six time points per day, from
      wakeup to bedtime. Associations between personality and cortisol rhythms were
      examined using multilevel growth curve modeling. Neuroticism (N) and introversion
      (I) were significantly and differentially associated with features of diurnal
      cortisol patterns. Specifically, a significant N x gender interaction was
      observed, demonstrating flatter cortisol rhythms across the waking day among male
      participants with higher N. Elevated I, however, was associated with lower
      cortisol awakening responses for both male and female participants, and higher
      cortisol at the time of waking for male participants only. The present study
      supports personality as a significant predictor of diurnal cortisol patterns in
      late adolescence, after accounting for the effects of demographic and health
      covariates, and suggests that gender plays a role in moderating associations
      between personality and cortisol.

PMID- 18809261
TI  - Prion and anti-codon usage: does infectious PrP alter tRNA abundance to induce
      misfolding of PrP?
AB  - The "protein-only" hypothesis of prion diseases views the infectious agent as
      devoid of nucleic acids and consisting of misfolded prion proteins (PrP(Sc))
      which, upon infiltration into host cells, act as a template that induces
      transformation of wild-type protein (PrP(C)) to the pathological form by unknown
      mechanisms. The two isoforms are identical in amino-acid composition. By analogy
      to reported "silent" mutations in which utilization of relatively rare tRNAs
      alter protein folding pattern, we postulate that misfolded PrP(Sc) alters tRNAs
      abundance in prion-infected cells and results in different rates of co
      translational folding of PrP, leading to the formation of additional misfolded
      PrP(Sc). We analyze experiments that might link tRNAs to prions. This concept of
      "PrP-seed and tRNA-soil" envisages a vicious cycle in which PrP(Sc) levels govern
      specific tRNA usage, whose alteration subsequently transforms resident PrP(C) to
      PrP(Sc), causing the cycle to repeat itself ad infinitum.

PMID- 18809262
TI  - Can insulin resistance be reversed by insulin therapy?
AB  - Insulin resistance (IR) is a state of decreased tissue sensitivity to insulin,
      which commonly exists in patients with metabolic syndrome and diabetes, and leads
      to compensatory hyperinsulinemia to maintain normoglycemia. It is characterized
      by pathway-specific inhibition of the PI3K/Akt signaling, which concerns the
      positive actions of insulin including glucose and lipid metabolism, while other
      pathways including the Ras/MAPK pathway, which accounts for the negative actions
      of insulin such as stimulation of smooth muscle proliferation and secretion of
      endothelin-1, stay unaffected. Thus it was concerned that insulin therapy may
      exacerbate the negative effects of insulin in IR states. However, treatment of
      diabetes with insulin in clinical practice showed uniformly beneficial rather
      than harmful results. So we hypothesize that insulin therapy may itself reverse
      insulin resistance, thus avoiding magnification of the MAPK pathway-related
      deleterious effects. The mechanisms may include the recently revealed anti
      inflammatory effects of insulin as well as its conventional glucose and free
      fatty acids lowering effects, and possibly may also include changes in body fat
      distribution and plasma adiponectin level. Whether there are direct mechanisms
      that insulin therapy modulates insulin sensitivity remains to be investigated.

PMID- 18809265
TI  - The putative penicillin-binding proteins 1 and 2 are important for viability,
      growth and cell morphology of Brucella melitensis.
AB  - The penicillin-binding proteins (PBPs) are enzymes that regulate the assembly of
      the peptidoglycan layer of the bacterial cell wall. The genome of Brucella
      melitensis strain 16M possesses seven pbp genes: three in pbp-1 family
      (designated as 1A, 1B, and 1C); one in pbp-2 family; and three in pbp-6 family
      (designated as 6A, 6B, and 6C). We investigated the importance of pbp-1 and pbp-2
      genes to viability, cell morphology and infectivity of B. melitensis. A
      recombinant B. melitensis strain (designated 16MDeltapbp1C) was generated by
      disrupting the pbp-1C of strain 16M by allelic exchange. This strain produced
      nearly 20% smaller colonies on trypticase soy agar plates, and grew slower in
      trypticase soy broth compared to the strain 16M. Electron microscopy revealed
      that strain 16M exhibited native cocco-bacillus morphology, while 16MDeltapbp1C
      possessed a spherical morphology. Strain 16MDeltapbp1C did not differ from strain
      16M in terms of recovery from infected mouse macrophage cell line J774.1, or
      recovery from spleens of infected BALB/c mice, suggesting that pbp-1C is
      dispensable for intracellular persistence of B. melitensis. Expression of mRNA of
      fixR, the gene downstream of pbp-1C was similar between the strains 16M and
      16MDeltapbp1C suggesting that disruption of pbp-1C did not induce any polar
      effects. Multiple attempts to mutate pbp-1A, pbp-1B, or pbp-2 genes failed, most
      probably because these genes are indispensable for viability of B. melitensis.
      Our findings suggest that pbp-1C regulates in vitro growth and cell morphology,
      whereas pbp-1A, pbp-1B, and pbp-2 are essential for viability of B. melitensis.

PMID- 18809264
TI  - Caffeinated energy drinks--a growing problem.
AB  - Since the introduction of Red Bull in Austria in 1987 and in the United States in
      1997, the energy drink market has grown exponentially. Hundreds of different
      brands are now marketed, with caffeine content ranging from a modest 50 mg to an
      alarming 505 mg per can or bottle. Regulation of energy drinks, including content
      labeling and health warnings differs across countries, with some of the most lax
      regulatory requirements in the U.S. The absence of regulatory oversight has
      resulted in aggressive marketing of energy drinks, targeted primarily toward
      young males, for psychoactive, performance-enhancing and stimulant drug effects.
      There are increasing reports of caffeine intoxication from energy drinks, and it
      seems likely that problems with caffeine dependence and withdrawal will also
      increase. In children and adolescents who are not habitual caffeine users,
      vulnerability to caffeine intoxication may be markedly increased due to an
      absence of pharmacological tolerance. Genetic factors may also contribute to an
      individual's vulnerability to caffeine-related disorders including caffeine
      intoxication, dependence, and withdrawal. The combined use of caffeine and
      alcohol is increasing sharply, and studies suggest that such combined use may
      increase the rate of alcohol-related injury. Several studies suggest that energy
      drinks may serve as a gateway to other forms of drug dependence. Regulatory
      implications concerning labeling and advertising, and the clinical implications
      for children and adolescents are discussed.

PMID- 18809266
TI  - The transition to oral feeding in low-risk premature infants: relation to infant
      neurobehavioral functioning and mother-infant feeding interaction.
AB  - BACKGROUND: The achievement of oral feeding is a critical task for the premature
      infant-mother dyad, yet neurobehavioral and relational factors associated with
      feeding difficulties of low-risk premature infants during hospitalization are not
      well understood. AIM: To examine the relations between infant neurobehavioral
      functioning, the transition to oral feeding, and the emerging mother-infant
      feeding relationship in premature infants. STUDY DESIGN AND SUBJECTS: Ninety
      seven low-risk premature infants (birth weight>1000 g; gestational age>30 weeks)
      and their mothers were followed at the NICU. Neurobehavioral functioning was
      assessed with the Rapid Neonatal Neurobehavioral Assessment Procedure. OUTCOME
      MEASURES: The duration of the transition to oral feeding and specific feeding
      difficulties during the transition were assessed. Infant feeding robustness, suck
      and milk transfer rates, and maternal adaptability, affect, intrusiveness and
      distractibility were coded from videotaped mother-infant feeding interactions
      prior to discharge from the NICU. RESULTS: Thirty percent of the infants
      presented feeding difficulties during the transition to oral feedings. Infants
      with abnormal neurobehavioral functioning (37% of the cohort) showed more feeding
      difficulties, slower suck rates, and lower feeding robustness, and their mothers
      displayed less adaptive and more intrusive behavior. Maternal intrusiveness was
      related to lower feeding robustness and to lower suck and milk transfer rates.
      Neurobehavioral functioning and maternal feeding behavior predicted feeding
      robustness. CONCLUSIONS: Less intact neurobehavioral functioning in the neonatal
      period is related to difficulties during the transition to oral feeding and to
      less optimal early mother-infant feeding interactions. Low-risk premature infants
      with poor neurobehavioral functioning should receive special attention and care.

PMID- 18809267
TI  - The effect of VEGF on the temporal-spatial change of alpha-tubulin and cortical
      granules of ovine oocytes matured in vitro.
AB  - The effects of vascular endothelial growth factor (VEGF) on the temporal-spatial
      change of alpha-tubulin and cortical granules (CGs) in ovine oocytes matured in
      vitro were studied using human recombinant VEGF(165) at 5 ng/ml in maturation
      media. Immunofluorescence, confocal microscopy and orcein staining were used to
      evaluate cell cycle-dependent modifications in nuclear configuration, quality of
      the metaphase II oocytes, microtubule organizing centers (MTOCs) translocation,
      temporal and spatial redistribution of alpha-tubulin and CGs in ovine oocytes
      undergoing in vitro maturation. The percentage of oocytes that reached metaphase
      II (M-II) in the VEGF-treated and the control groups were 87.08% and 80.03%
      (P=0.077) at 18 h and 87.42% and 83.89% (P=0.28) at 24h, respectively. The
      percentages of oocytes displaying a normal distribution of alpha-tubulin and
      chromosomes in M-II increased significantly (P=0.015) in the VEGF group (77.50%)
      compared to the control (62.60%). The percentage of oocytes with CGs transfering
      completely in cortex was significantly higher (P=0.002) in the VEGF group
      (79.24%) than in the control group (60.97%). VEGF promoted the MTOCs domains to
      disappear from the cortex and stimulated assembly of alpha-tubulin around
      chromosome domains when germinal vesicle breakdown (GVBD) was commencing. In
      conclusion, VEGF may improve the quality of nuclear and cytoplasmic maturation of
      ovine oocytes in vitro by its effect on temporal and spatial translocation or
      redistribution of alpha-tubulin and CGs and on the normal distribution of nuclear
      configuration.

PMID- 18809268
TI  - Benign and malignant salivary gland diseases in children A retrospective study of
      549 cases from the Salivary Gland Registry, Hamburg.
AB  - OBJECTIVE: Tumors of salivary glands in children are rare. Basically all types of
      salivary gland diseases during the period of childhood are described. The
      incidences of salivary gland tumors in children (0-14 years) differ completely
      from those in adults. Especially the malignant neoplasms are very rarely
      described in literature. Only some collective reviews and case reports try to
      summarize frequency, distribution concerning sex and age, morphology and
      localization. METHODS: In our study we were able to draw data from the Hamburg
      Salivary Gland Registry, concerning the last 25 years regarding histopathological
      diagnosis, age, gender and localisation of the pathologies. Findings were
      compared to other studies. Most of the specimens were presented by the Clinic for
      Otorhinolaryngology and Head and Neck Surgery, University Hamburg, Eppendorf. As
      a reference centre for salivary gland diseases some material was sent by other
      institutions. RESULTS: This study will give a detailed survey of salivary gland
      diseases and tumors in children up to the age of 14 which have undergone surgical
      therapy/biopsy. We present the general distribution of the different
      tumors/diseases, the distribution in certain age groups and the various
      locations. 549 cases could be examined. Comparing the distribution of malignant
      tumors with other studies, the epithelial-myoepithelial carcinomas followed by
      salivary duct carcinomas represent the largest group in childhood. CONCLUSIONS:
      The study shows that comparing to adulthood different tumors play an important
      role in adolescence. The distribution of tumors in childhood may help in
      diagnostic. Further many salivary gland diseases in childhood underwent
      surgery/biopsy although this is not supposed to be the proper treatment. The
      study shows that the right diagnosis most often can only be reached by surgery
      and histology.

PMID- 18809269
TI  - Acute disseminated encephalomyelitis in an infant with incontinentia pigmenti.
AB  - We report the case of a female Japanese infant who was diagnosed with
      incontinentia pigmenti (IP) on the basis of the clinical and pathological
      findings of characteristic skin lesions and the detection of deletion in the
      nuclear factor-kappa B essential modulator gene at Xq28. The patient developed
      repetitive seizures at the age of 7 months when she was diagnosed with acute
      disseminated encephalomyelitis (ADEM), an inflammatory demyelinating disease of
      the central nervous system that often occurs after vaccination or infection. The
      causative infectious agent in this patient seemed to be Mycoplasma pneumoniae
      because of the increased titer of its serum antibody and the detection of its DNA
      in the initial cerebrospinal fluid sample. This patient showed significant
      improvement on receiving immunosuppressive therapy with corticosteroids. This is
      the second case report presenting an IP patient susceptible to ADEM, and
      therefore, ADEM should be considered early in the differential diagnosis of acute
      neurological illness for IP patients.

PMID- 18809270
TI  - [Computerized list and multiresistant bacteria epidemic].

PMID- 18809271
TI  - [First case of vancomycin-resistant Enterococcus faecalis in Algeria].

PMID- 18809272
TI  - Time-of-flight MR angiography at 3T versus digital subtraction angiography in the
      imaging follow-up of 51 intracranial aneurysms treated with coils.
AB  - OBJECTIVE: To compare 3D time-of-flight MR angiography (TOF-MRA) at 3 Tesla (3T)
      with digital subtraction angiography (DSA) for the evaluation of intracranial
      aneurysm occlusion after endovascular coiling. METHODS: In a prospective study,
      51 consecutive patients (25 females, 26 males; median age, 51 years) with 51
      saccular aneurysms treated with endovascular coiling underwent simultaneous DSA
      and 3T TOF-MRA at follow-up. DSA and TOF-MRA images were analyzed independently
      by two senior neuroradiologists. Findings were assigned to 1 of 3 categories in
      the Raymond classification: complete obliteration, residual neck or residual
      aneurysm. Agreement between observers and techniques was evaluated using kappa
      statistics. RESULTS: DSA images were not interpretable for one patient.
      Interobserver agreement was determined as excellent for DSA (kappa=0.86) and TOF
      MRA (kappa=0.80). After reaching a consensus, DSA follow-up showed 26 (51%)
      complete obliterations, 20 (39%) residual necks and 4 (8%) residual aneurysms.
      TOF-MRA showed 23 (45%) complete obliterations, 22 (43%) residual necks and 6
      (12%) residual aneurysms. Comparison between TOF-MRA and DSA showed excellent
      agreement between the techniques (kappa=0.86). In the four cases that were
      misclassified, TOF-MRA findings were assigned to a higher class than for DSA.
      CONCLUSION: TOF-MRA at 3T is at least as efficient as DSA for the evaluation of
      intracranial aneurysm occlusion after endovascular treatment with detachable
      coils. We suggest that TOF-MRA at 3T might be used as the primary method for
      imaging follow-up of coiled intracranial aneurysms.

PMID- 18809273
TI  - Optimised sample handling in association with use of the CMA 600 analyser.
AB  - A large degree of variability for batched analysis of serially collected
      microdialysis samples measured with the CMA 600 analyser has been described. This
      study was designed to identify sources of variability related to sample handling.
      Standard concentrations of four solutes were placed in microdialysis vials and
      then stored and analysed at intervals. Results were analysed for variability
      related to vial and cap type, duration and temperature of storage, centrifugation
      and re-analysis. The main results were that centrifugation of samples reduced
      variability. When a batch of 24 samples was analysed, the use of crimp caps
      reduced evaporation. Samples in glass vials with crimp caps could be stored in a
      refrigerator for up to 14 days without large variability in concentration
      compared to plastic vials which demonstrated variability already when stored for
      more than 1 day. We conclude that variability in microdialysis results can occur
      in relation to storage and analysis routines if routines are not optimised
      concerning evaporation. Centrifugation before analyses, glass vials with crimp
      caps even during frozen storage, and attention to minimal times for samples to be
      uncapped during analysis all contribute to minimise variability in the handling
      and analysis of microdialysis samples.

PMID- 18809274
TI  - Paeoniflorin suppress NF-kappaB activation through modulation of I kappaB alpha
      and enhances 5-fluorouracil-induced apoptosis in human gastric carcinoma cells.
AB  - OBJECTIVE: We sought to determine whether paeoniflorin enhances 5-fluorouracil
      induced apoptosis in human gastric carcinoma cells, and, if so, to determine the
      relationship between this apoptosis and NF-kappaB activation. METHODS:
      Paeoniflorin was diluted to different concentrations and added to gastric
      carcinoma cells (SGC-7901) at different times. Western blot was used to test the
      expression of NF-kappaB in nuclear and I kappaB alpha, p-I kappaB alpha, IKK
      alpha in cytoplasm. Further, the intranuclear expression of NF-kappaB was
      confirmed by ELISA assay. The impact of paeoniflorin and 5-fluorouracil on cell
      apoptosis of gastric carcinoma cells was estimated by flow cytometry. RESULTS:
      Paeoniflorin revealed dramatic inhibition of NF-kappaB activity in the nuclei of
      the cells. The inhibition pattern of NF-kappaB was exhibited in a time- and dose
      dependent manner, which was confirmed by Western blot and ELISA. Decreased
      nuclear translocation of NF-kappaB induced by paeoniflorin was found by
      preventing I kappaB alpha phosphorylation. Moreover, 5-fluorouracil-induced cell
      apoptosis was promoted by paeoniflorin in gastric carcinoma cells. CONCLUSIONS:
      Paeoniflorin can inhibit NF-kappaB activity of SGC-7901 cells, and enhance 5
      fluorouracil-induced apoptosis of gastric carcinoma cells.

PMID- 18809275
TI  - L-carnitine supplementation in patients with advanced cancer and carnitine
      deficiency: a double-blind, placebo-controlled study.
AB  - Carnitine deficiency is prevalent in populations with chronic illness, including
      cancer. In a recent open-label study, L-carnitine supplementation was well
      tolerated and appeared to improve fatigue and other outcomes in cancer patients.
      To further evaluate this finding, adult patients with advanced cancer, carnitine
      deficiency (free carnitine more than 35 micromol/L for males or less than 25
      micromol/L for females, or acyl/free carnitine ratio of more than 0.4), moderate
      to severe fatigue, and a Karnofsky Performance Status (KPS) score of 50 or more,
      were randomly assigned to receive either L-carnitine (0.5 g/day for two days,
      followed by 1g/day for two days, and then 2g/day for 10 days) or placebo. This
      double-blind phase was followed by an open-label phase, during which all patients
      received L-carnitine supplementation for two weeks. Outcomes included the fatigue
      subscale of the Functional Assessment of Cancer Therapy-Anemia (FACT-An), the
      Linear Analog Scale Assessments (LASA), the Mini-Mental State Exam (MMSE), and
      the KPS. Twenty-nine patients (12 placebo, 17 L-carnitine) were included in the
      intent-to-treat (ITT) analysis. From baseline to the end of the double-blind
      phase, serum total and free L-carnitine increased from 32.9+/-3.8 to 56.6+/-20.5
      (P=0.004), and from 22.9+/-19.4 to 45.3+/-17.2 (P=0.004), respectively, in the L
      carnitine-treated group, and from 28.2+/-10.2 to 36.2+/-8.7 (P=ns), and from
      22.6+/-7.9 to 28.7+/-8.6 (P=ns) in the placebo group, respectively. The planned
      ITT analysis revealed no significant improvement in any of the study's endpoints,
      and these negative findings were not different when data from two patients who
      did not adhere to the protocol were eliminated. However, an exploratory covariate
      analysis that excluded these two protocol violators and included outcome data
      from both the double-blind and open-label phases demonstrated significantly
      improved fatigue on the FACT-An fatigue subscale (P<0.03), and significantly
      improved FACT-An functional well-being subscale (P<0.03), and KPS (P<0.003), in
      the group that started with L-carnitine during the double-blind phase. These data
      do not support the conclusion that L-carnitine in the doses tested reverses
      cancer-related fatigue in carnitine-deficient patients. However, L-carnitine
      supplementation does increase L-carnitine serum levels, and the positive findings
      in an exploratory analysis justify a larger study to determine if this strategy
      could be of benefit for a subpopulation of cancer patients.

PMID- 18809276
TI  - A framework for generalizability in palliative care.
AB  - Palliative medicine has only recently joined the ranks of evidence-based medical
      subspecialties. Palliative medicine is a rapidly evolving field, which is quickly
      moving to redress its historical paucity of high-quality research evidence. This
      burgeoning evidence base can help support the application of evidence-based
      principles in palliative and hospice clinical care and service delivery. New
      knowledge is generally taken into practice relatively slowly by established
      practitioners. At present, the translation of evidence into palliative and
      hospice care clinical practice lags behind emerging research evidence in
      palliative care at even greater rates for three critical reasons: 1) the
      application of research results to specific clinical subpopulations is
      complicated by the heterogeneity of palliative care study subpopulations and by
      the lack of a recognized schema for describing populations or services; 2)
      definitional issues in service provision are, at best, confusing; and 3)
      fundamental research concepts (e.g., external validity, effect size,
      generalizability, applicability) are difficult to apply meaningfully in
      palliative care. This article provides a suggested framework for classifying
      palliative care research subpopulations and the clinical subpopulations to which
      the research findings are being applied to improve the ability of clinicians,
      health planners, and funders to interpret and apply palliative care research in
      real-world settings. The framework has five domains: patients and caregivers;
      health professionals; service issues; health and social policy; and research.

PMID- 18809278
TI  - Distal graft anastomosis using a tapered elephant trunk in an inflammatory
      aneurysm.
AB  - Graft replacement of an inflammatory abdominal aortic aneurysm is rather
      troublesome due to the marked adhesion to surrounding organs and thickened wall,
      which is mostly too hard and inflexible to allow the artery to be fitted to a
      prosthetic graft. For one such case, we developed a novel and unique technique
      for a distal anastomosis using a tapered elephant trunk. This technique was
      designed on the assumption of further aneurysmal changes and enabled us to create
      a secure anastomosis at the enlarged inflammatory part of the common iliac
      artery. The distal flow to both the external and internal iliac arteries was well
      maintained without any complications.

PMID- 18809277
TI  - Arteriovenous fistula construction using femoral vein in the thigh and upper
      extremity: single-center experience.
AB  - The objective of this study was to determine the outcome of femoral vein (FV)
      access as either a FV thigh transposition or upper extremity FV translocation.
      This is a retrospective review of all end-stage renal disease (ESRD) patients who
      underwent FV access at the University of Colorado Health Sciences Center from
      December 2004 to May 2007. Demographics, number of prior access procedures, FV
      dialysis access procedure, periprocedural complications, mean follow-up,
      secondary access-related procedures, and access function were recorded.
      Complications were subdivided into FV harvest site- and ischemia-related.
      Nineteen patients underwent FV access during the study period: 10 underwent FV
      thigh transpositions and nine underwent upper extremity FV translocations. The
      median number of prior access procedures was two. The median hospital stay was 3
      days, and there were no perioperative deaths. Eight patients had FV harvest site
      complications: six lymphoceles, one AVF infection requiring ligation, and one
      compartment syndrome requiring fasciotomy. Three (16%) patients had ischemic
      complications: one required ligation of the AVF and two required distal
      revascularization interval ligation. Seventy-nine percent of patients had a
      functioning access at a mean follow-up of 6 months (range 23 days to 3 years).
      Four FV arteriovenous accesses required one or more endovascular procedures to
      maintain function at 12 months. The use of FV access in ESRD is durable at
      intermediate follow-up but has significant morbidity. FV access should be
      reserved for good-risk patients who have exhausted other autogenous options.

PMID- 18809279
TI  - An unusual case of leiomyosarcoma of the inferior vena cava in a patient with a
      duplicated inferior vena cava.
AB  - Leiomyosarcoma of primary vascular origin is a rare primary soft tissue tumour,
      which arises mainly from the inferior vena cava (IVC). Clinical symptoms depend
      upon the size and location of the tumour and presents usually with abdominal
      pain, palpable mass and weight loss. Complete surgical resection with clear
      surgical margin plays a central therapeutic role. The effect of chemotherapy and
      radiation therapy remains to be evaluated. We report a 64 year old Chinese female
      who presented with abdominal mass and pain associated with weight loss and was
      subsequently diagnosed with inferior vena cava leiomyosarcoma. She underwent
      successful surgical resection but unfortunately developed recurrence of tumour 12
      month post-operative. She was also found to have a duplicated inferior vena cave
      which allowed reconstitution of venous return from the lower limbs after surgical
      resection of the IVC tumour. We discuss the surgical treatment and results of
      leiomyosarcoma of the IVC.

PMID- 18809280
TI  - Plication as primary treatment of steal syndrome in arteriovenous fistulas.
AB  - Steal syndrome is an uncommon complication following hemodialysis access. Options
      for management include fistula ligation, banding, and distal revascularization
      with interval ligation (DRIL). Plication is another technique that is simple yet
      infrequently reported. We have adopted plication as the procedure of choice for
      steal syndrome following autologous arteriovenous fistula (AVF) creation. We
      report seven cases managed by plication. All had immediate resolution of symptoms
      (Table I). At follow-up, all AVFs were patent and continued to be used for
      hemodialysis. However, one patient experienced recurrence of symptoms and
      required re-plication. In conclusion, plication of the autologous AVF represents
      a simple alternative to the management of steal syndrome.

PMID- 18809281
TI  - Dynamic aortic changes in patients with thoracic aortic aneurysms evaluated with
      electrocardiography-triggered computed tomographic angiography before and after
      thoracic endovascular aneurysm repair: preliminary results.
AB  - The purpose of this study was to utilize dynamic computed tomographic angiography
      (CTA) on pre- and postoperative thoracic endovascular aneurysm repair (TEVAR)
      patients to characterize cardiac pulsatility-induced aortic motion on essential
      TEVAR proximal sealing zones and to study the influence of endograft placement.
      Six pre- and six postoperative dynamic CTA studies were obtained in six patients
      with thoracic aortic aneurysms (TAAs) undergoing TEVAR. Data were acquired using
      a retrospective electrocardiography-triggered dynamic CTA scan, with eight
      reconstructed phases over the cardiac cycle. Scans were acquired during a single
      breath hold. Multiplanar reconstructions were made perpendicular to the aorta at
      five surgically relevant anatomical thoracic landmarks: 1 cm proximal to the
      innominate trunk, 1 cm proximal and 1 cm distal to the left subclavian artery,
      and 1 cm proximal and 3 cm distal to the proximal end of the stent. After
      segmentation of the aortic lumen in the images, diameter change and area change
      over the cardiac cycle were measured. Diameter change was measured through the
      center of mass of the aortic lumen, and the average change over 180 axis is
      presented. We found significant distention of the thoracic aortic arch and
      descending thoracic aorta during the cardiac cycle before and after TEVAR.
      Distention ranged 3-12% in diameter and 2-20% in area. This distention was
      preserved after TEVAR. Patients with TAA experience aortic diameter and area
      changes during the cardiac cycle. The magnitude, and hence the clinical
      importance, of this aortic distention varies among patients. After stent-graft
      placement, aortic distention throughout the cardiac cycle is preserved. This may
      have major implications for correct sizing of the endograft as well as for stent
      graft design and durability as the forces on the stents may be much larger after
      implantation than initially anticipated by stent manufacturers.

PMID- 18809282
TI  - The management of mycotic femoral pseudoaneurysms in intravenous drug abusers.
AB  - Mycotic femoral pseudoaneurysms, particularly in the drug-abusing population,
      pose a difficult problem to the vascular surgeon. Management ranges from ligation
      with debridement to extra-anatomical bypass. This study reviewed the management
      of mycotic femoral pseudoaneurysms presenting in intravenous drug abusers to an
      inner city tertiary referral center. Between 2001 and 2006, 11 cases presenting
      in nine patients were treated. The mean age was 30.7 years with a male-to-female
      ratio of 1:2. Eight patients had a positive viral status for the human
      immunodeficiency virus and/or hepatitis C. Two patients re-presented with a
      contralateral pseudoaneurysm. A combination of groin pain and swelling was the
      most common presentation. Two patients presented with significant hemorrhage. The
      diagnosis was confirmed by ultrasound in the majority of cases. Nine cases were
      managed with arterial ligation and debridement of the necrotic tissue. The two
      remaining cases were managed with ultrasound-guided thrombin injection and
      arterial puncture closure. On follow-up, one patient required a below-knee
      amputation following reinjection into the postoperative wound site. One further
      patient underwent a fifth metatarsal amputation due to ischemia. Ligation and
      debridement are well tolerated in the majority of drug-abusing patients diagnosed
      with mycotic femoral pseudoaneurysms.

PMID- 18809283
TI  - Celiomesenteric trunk aneurysm.
AB  - A celiomesenteric trunk (CMT) is an extremely rare anatomic variant that consists
      of celiac and superior mesenteric arteries having a common origin from the aorta.
      CMT accounts for less than 1% of all splanchnic artery anomalies. Aneurysm
      involving a CMT is an even rarer vascular abnormality, and, to our knowledge,
      only eight cases of CMT aneurysm have been reported in literature. We describe a
      case of the incidental finding of CMT aneurysm in an asymptomatic patient. It was
      found after dorsolumbar column radiography and successive computed tomography and
      arteriography confirmed the diagnosis. Even if asymptomatic, we decided to repair
      it surgically with aneurysmectomy and suture of the neck due to risk of rupture.

PMID- 18809284
TI  - Endovascular management versus surgery for proximal subclavian artery lesions.
AB  - Current management of subclavian artery (SA) lesions is controversial. Subclavian
      to-carotid artery transposition (SCT) may be challenging but exhibits
      unparalleled long-term results. Stent-supported percutaneous transluminal
      angioplasty (sPTA) is technically easier but not always feasible. Long-term
      results and comparisons have not been published. We compared both methods
      performed by vascular surgeons. Data were collected prospectively with
      retrospective analysis at a tertiary-care center. sPTA was performed through a
      retrograde transbrachial access using self-expanding nitinol stents. Open surgery
      was SCT only. Society for Vascular Surgery/International Society of
      Cardiovascular Surgery reporting standards were applied. Seventy-four patients
      underwent treatment from January 1995 to August 2007 (median age 62.6 years, 40
      female; left-sided pathology 60 [81.1%]; risk factors: hypertension 45 [60.8%],
      dyslipidemia 47 [63.5%], diabetes 21 [28.4%], smoking 43 [58.1%], SA occlusion 50
      [67.6%]). Forty patients (54.1%) underwent primary sPTA (62.5% occlusions) and 34
      SCT (73.5% occlusions). The two groups were comparable with regard to risk
      factors. In 12 patients occlusions could not be recanalized (30%), and in two
      stents failed within 1 month (both for stenosis). All but one underwent
      subsequent uneventful SCT. All SCTs were successful. No risk factor could be
      identified for treatment failure except sPTA (p = 0.002, Fisher's exact test).
      Median follow-up was 50.1 months with sPTA and 52.6 months with SCT. No procedure
      failed during follow-up in either group. sPTA can be performed successfully by
      surgeons. Primary sPTA failed in 48% of occlusions (30% of all sPTAs). Prediction
      of failure is not possible. According to our experience, we recommend primary
      sPTA for SA stenosis and surgery for SA occlusions.

PMID- 18809285
TI  - Idiopathic thoracic aortic aneurysm at pediatric age.
AB  - A 6-year-old-boy presented with epigastric pain and vomiting over 1 year. Chest X
      ray and esophagogastric transit showed a mediastinal mass. A chest computerized
      tomography angiogram demonstrated a descending thoracic aortic aneurysm.
      Analytical determinations carried out were all negative. The aneurysm was
      surgically repaired using a Dacron patch. The anatomopathological study described
      atherosclerotic lesions with calcifications, compatible with an atherosclerotic
      aneurysm wall. Aneurysms are uncommon in the pediatric population. Usually, no
      pathogenesis can be determined, and thus, such cases are grouped as idiopathic.
      Direct repair with or without patch is a therapeutic alternative in pediatric
      aneurysms and can allow the growth of the aortic circumference.

PMID- 18809286
TI  - A singular case of iatrogenic axillofemoral bypass disruption: a dramatic event
      treated by a lucky combined approach.
AB  - Proximal disruption of an axillofemoral bypass is a catastrophic event rarely
      caused by a posttraumatic anterior dislocation of the shoulder. Herein, we
      present a 74-year-old man with a painful dislocation of the right shoulder that
      was successfully reduced. Three hours later he had hemodynamic shock with an
      expanding and pulsating hematoma at the level of the right shoulder, pectoral and
      infraclavicular region. Surgical exposure of the right brachial artery was
      carried out, and intraoperative angiography revealed a proximal anastomotic
      leakage. The distal ballooning improved the hemodynamic status, and by a redo
      infraclavicular incision the hematoma was drained. The arterial leak was repaired
      by an 8 mm polytetrafluoroethylene interposed graft between the axillary artery
      and existing graft. The utility of a combined approach (endovascular + open
      surgical) is discussed.

PMID- 18809287
TI  - The utility of the StarClose arterial closure device in patients with peripheral
      arterial disease.
AB  - The StarClose (Abbott Vascular, Redwood City, CA) arterial closure device
      utilizes an extraluminal nitinol clip to establish hemostasis. The purpose of
      this study was to determine the safety and efficacy of StarClose from a
      prospective peripheral arterial disease (PAD) registry. Over an 18-month time
      interval, 500 StarClose devices were used in 378 consecutive patients with
      symptomatic PAD after diagnostic and/or therapeutic endovascular cases. Patient
      demographics along with objective criteria including duplex ultrasound images,
      common femoral artery flow velocities, and ankle-brachial indexes (ABIs) were
      analyzed before and after StarClose placement. All outpatients received
      prophylactic antibiotic (one dose), periprocedural heparin (without protamine
      reversal), and antiplatelet therapy. Aspirin and clopidogrel (Plavix) was used
      for all patients undergoing therapeutic intervention. There were 378 patients who
      underwent procedures for aortoiliac or infrainguinal PAD, 99 of which were
      bilateral. Of the 500 arteriotomy closures, 296 were therapeutic interventions
      with sheath sizes of 6-8 F in the common femoral artery. The diagnostic studies
      (n = 204 arteriotomies) were performed with a 5F sheath. The technical success in
      achieving hemostasis was 97.2%; only 14 devices had a deployment problem
      requiring prolonged manual compression. Median length of stay was 157 min for
      patients done on an outpatient basis. Eleven of 260 (4.2%) on duplex follow-up
      had a doubling of the peak systolic velocity, only one of which was symptomatic.
      Late follow-up showed 42 of 360 (11.7%) with a drop in ABI >0.10. Nine major
      complications (2.0%) were identified in follow-up. The StarClose closure device
      has a low major complication rate and is safe and efficacious in patients with
      PAD, although stenosis at the arteriotomy site may occur. The device has achieved
      rapid hemostasis without need for anticoagulant reversal and requires
      significantly less time to ambulation than manual compression.

PMID- 18809288
TI  - Open surgical repair of descending thoracic aortic aneurysms in the endovascular
      era: a 9-year single-center study.
AB  - The purpose of this study was to present a single center's experience with
      elective treatment of descending thoracic aortic aneurysms (DTAAs) in the
      endovascular era. From July 1997 to May 2005, we operated on 173 patients for
      DTAA. A total of 52 patients (30.1%) underwent endovascular stent-graft repair
      (group I). Endovascular repair was carried out exclusively in high-surgical risk
      patients in whom preoperative spinal cord arteriography usually demonstrated that
      the origin of the Adamkiewicz artery was located outside the zone to be covered
      by the stent graft. The remaining 121 patients (69.9%) underwent open surgical
      repair (group II), with partial cardiopulmonary bypass in 78 cases (64.5%) and
      deep hypothermic circulatory arrest in 43 (35.5%). The two treatment groups
      differed significantly with regard to age, prevalence of chronic obstructive
      pulmonary disease, number of aneurysms involving the upper segment or full length
      of the descending thoracic aorta, and percentage of patients in whom spinal cord
      arteriography was either deemed unnecessary or demonstrated that the origin of
      the Adamkiewicz artery was located within the coverage zone. In-hospital
      mortality was 15.4% (8/52) in group I vs. 5.0% (6/121) in group II (p = 0.02).
      Five deaths after endovascular repair were due to technical causes. All
      neurological deficits due to spinal cord ischemia (9/121, 7.4%) including 3.3% of
      irreversible flaccid paraplegia occurred in group II (p = 0.04). The findings of
      this study show that open surgical repair achieves excellent results when high
      risk surgical candidates are recommended for endovascular repair. However, since
      preoperative spinal cord arteriography was a selection criterion for endovascular
      repair, the improvement in mortality was accompanied by a concentration of spinal
      cord ischemic complications in the patients having open surgical repair. The high
      mortality associated with endovascular repair in our series should decrease as
      deployment skill and endovascular technology improve.

PMID- 18809289
TI  - Arteriovenous graft with outflow in the proximal axillary vein.
AB  - Arteriovenous access can result in complications including extremity ischemia and
      swelling. Use of the nondominant upper extremity is preferred because
      complications will result in less severe disability. The distal axillary vein in
      the axilla is usually considered to be the end point for arteriovenous access in
      the upper extremity. Vascular surgeons are familiar with exposure of the proximal
      axillary artery via an infraclavicular incision. The axillary vein is also easily
      exposed through this technique. Use of this vein for arteriovenous graft outflow
      can preserve the dominant arm for future use. Nine patients with arteriovenous
      grafts with venous outflow in the proximal arm for future use. All patients had
      exposure to the proximal axillary vein via an infraclavicular incision. There
      were six women and three men. All patients had multiple failed access in the
      ipsilateral extremity. One patient had a loop configuration graft, while the six
      others had a straight graft with arterial inflow via the brachial artery. One
      patient had a bovine mesenteric vein graft, while the remaining six had expanded
      polytetrafluoroethylene grafts. Six of the seven patients had ambulatory surgery,
      while one patient was admitted postoperatively with mental status changes.
      Patency rates were 78%, with mean follow-up of 16 months. One patient had early
      failure due to steal and one patient failed at 22 months. Six of seven patients
      are alive at current follow-up. Three patients required secondary procedures
      including venous angioplasty (n=2) and subclavian artery stenting (n=1). The
      infraclavicular axillary vein can be used as an effective outflow for
      arteriovenous grafts. This procedure can be done as an outpatient surgery with a
      low complication rate. This procedure can preserve the dominant arm for future
      access and provides a possible alternative to surgery on another extremity.

PMID- 18809290
TI  - Laparoscopy-assisted left ovarian vein transposition to treat one case of
      posterior nutcracker syndrome.
AB  - We report one case of posterior nutcracker syndrome treated by left ovarian vein
      (LOV) transposition. A 36-year-old woman was suffering from nutcracker syndrome
      associated with pelvic congestion syndrome. Color duplex scan, computed
      tomographic scan, and angiography demonstrated a stenosis of a retroaortic left
      renal vein with proximal dilatation and incompetence of the LOV. The renocaval
      pullback gradient was 10 mm Hg. The LOV was harvested laparoscopically and
      transposed into the inferior vena cava. Completion angiography showed a patent
      reconstruction with no significant gradient. At day 4, an asymptomatic thrombosis
      was treated by thromboaspiration. Forty months later, the patient remained
      asymptomatic with a patent transposition. Posterior nutcracker syndrome is a rare
      condition. When associated with pelvic congestion syndrome due to LOV reflux, it
      can be treated by LOV transposition.

PMID- 18809291
TI  - Surgical repair of localized dissecting aneurysm originating from the infrarenal
      abdominal aorta.
AB  - Aortic dissection commonly affects the thoracic aorta and is associated with high
      morbidity and mortality rates. Localized dissections originating from the
      infrarenal abdominal aorta are extremely rare. We report a rare case of localized
      dissecting aneurysm originating from the infrarenal abdominal aorta in a 62-year
      old man. Open surgical repair was successfully performed without any
      complications.

PMID- 18809292
TI  - Long-term follow-up for superior vena cava filter placement.
AB  - The short-term effectiveness and safety placement of superior vena cava (SVC)
      filter in the treatment of upper extremity deep venous thrombosis in patients
      with contraindication to anticoagulation have been well documented. However, as
      opposed to the numerous reported experiences with inferior vena cava filter
      placement and its complications, there has been no documented long-term follow-up
      on SVC filter placement. We, therefore, reviewed our experience with SVC filter
      placement. A retrospective review was performed of the 154 cases of patients who
      underwent SVC filter placement between January 1994 and August 2005 at our
      institution. Seven additional patients had unsuccessful SVC filter placement due
      to widespread deep venous thrombosis. The data were evaluated for both insertion
      complications (pneumothorax, hemorrhage, filter misplacement) and long-term
      complications (pulmonary embolism, migration, caval occlusion). The follow-up
      included review of serial chest radiographs to evaluate for filter migration in
      patients who lived at least 60 days after filter insertion and had chest
      radiography performed (n = 40), patients' charts, clinic visits, and telephone
      contacts, hospital databases, city death records, and national databases. There
      were 69 males and 85 females with a mean age of 73.6 years (range, 16-96 years;
      +/-15.3 [SD] years). Follow-up ranged from 1 day to 3750 days (256.3 +/- 576 days
      [mean +/- SD]) and 5 patients were lost to follow-up. Of the 154 patients, 58
      survived longer than 60 days with mean follow-up of 628.4 days. All SVC filters
      (TrapEase, n = 38; Greenfield, n = 116) were successfully deployed in the 154
      patients. During the follow-up, 114 (74.0% mortality) of the patients died of
      chronic illness or from cancer complications. There were three cases of
      pericardial tamponade (1.9%), and one case of misplaced filter in innominate
      vein. There were no known cases of symptomatic pulmonary embolism, caval
      occlusion, pneumothorax, or filter migration. SVC filter placement is associated
      with a low incidence of complications with long-term follow-up. These data help
      to reaffirm the safety and effectiveness of SVC filter placement. However, SVC
      perforation in young males remains a significant issue.

PMID- 18809293
TI  - Incidence and outcome of filter occlusion during carotid artery stent procedure.
AB  - Recent reviews of device-specific complications using neuroprotection have
      addressed technical difficulties during delivery as well as adverse outcomes,
      intraoperative and 30-day. Little has been written, however, regarding the
      relevance of filter occlusion during the carotid stent procedure. A retrospective
      review was conducted of patients undergoing carotid artery stent procedures using
      a variety of neuroprotection devices from 2003 to 2007. Prospective databases
      from two institutions were examined for incidence and management of filter
      occlusions during procedures as well as adverse neurological events
      (intraoperative and 30-day) associated with filter occlusion. There were 283
      carotid artery stent procedures performed on 256 patients (163 male, 93 female):
      177 (62.5%) arteries were asymptomatic and 106 were symptomatic. Neurological
      adverse events occurred in six patients (2.1%); three of these resolved
      completely at 72 hr. Neuroprotection was used in 95% of all patients, and filters
      were used in 221 stent procedures: Boston Scientific Filter Wire (n = 81),
      Guidant Accunet (n = 100), Angioguard (n = 17), and Abbot Emboshield (n = 23).
      Filter occlusion occurred in 11 patients (4.9%) in whom this form of
      neuroprotection was employed: Angioguard (n = 5), Accunet (n = 2), Emboshield (n
      = 2), and EPI Filter wire (n = 2). Two of the 11 patients with filter occlusions
      suffered a neurological event. There was no correlation between filter occlusion
      and gender, symptoms, stent, or filter type (p > 0.05). Filter occlusion was
      managed with export catheter-directed aspiration in seven patients and with
      prompt filter retrieval in five patients. Filter occlusion is an infrequent event
      that does not appear to be filter-specific and can be managed successfully by
      catheter-directed aspiration or filter retrieval. The majority of patients with
      filter occlusion do not suffer from atheroemboli as a result of this occlusion.

PMID- 18809294
TI  - Role of interactive home telemedicine for early and protected discharge 1 day
      after carotid endarterectomy.
AB  - Our aim was to prove the feasibility and safety of a protocol for early and
      protected discharge 1 day after carotid endarterectomy (CEA) using a system of
      telemedicine (TMD) monitoring. Among 147 patients operated upon for 163 CEAs, we
      selected a group (A) of 36 patients fulfilling criteria for discharge 1 day after
      surgery. An electronic blood pressure manometer, a videophone, an
      antihypertensive drug (amlodipine), and a customer satisfaction questionnaire
      were given to every group A patient. With a video-communication program linked to
      the Web, we monitored every 4 hours (from 8:00 a.m. to 8:00 p.m.) for 2 days the
      surgical wound, blood pressure, and heart frequency of the patients. Other
      patients were included in group B. No differences regarding demographic
      characteristics, risk factors, carotid lesions, operative time, postoperative
      complications, or blood loss were noted between group A and group B. Twenty-one
      patients in group A were actually discharged 1 day after surgery. No cervical
      hematoma developed. Three hypertensive crises were treated successfully in group
      A. From the questionnaire a feeling of insecurity at discharge emerged, but it
      rapidly resolved. The overall cost of video connections was 25.39 +/- 0.25 Euros
      per patient. CEA can be safely done as 1-day surgery using a TMD monitoring
      system in selected cases. Our protocol allowed early discharge safely, leading to
      reduced hospital costs.

PMID- 18809295
TI  - Type A intramural hematoma presenting with acute right heart failure caused by
      compression of the main pulmonary artery: a case report.
AB  - Pulmonary artery obstruction is a rare complication of intramural hematoma of the
      ascending aorta. There were few reported cases presenting with right heart
      failure due to compression of the pulmonary trunk by intramural hematoma of the
      aorta.

PMID- 18809296
TI  - Training staff serving clients with intellectual disabilities: a meta-analysis of
      aspects determining effectiveness.
AB  - The last decades have seen increased emphasis on the quality of training for
      direct-care staff serving people with intellectual disabilities. Nevertheless, it
      is unclear what the key aspects of effective training are. Therefore, the aim of
      the present meta-analysis was to establish the ingredients (i.e., goals, format,
      and techniques) for staff training that are related to improvements of staff
      behaviour. Our literature search concentrated on studies that were published in a
      period of 20 years. Fifty-five studies met the criteria, resulting in 502 single
      subject designs and 13 n>1 designs. Results revealed important information
      relevant to further improvement of clinical practice: (a) the combination of in
      service with coaching-on-the-job is the most powerful format, (b) in in-service
      formats, one should use multiple techniques, and verbal feedback is particularly
      recommended, and (c) in coaching-on-the-job formats, verbal feedback should be
      part of the program, as well as praise and correction. To maximize effectiveness,
      program developers should carefully prepare training goals, training format, and
      training techniques, which will yield a profit for clinical practice.

PMID- 18809297
TI  - A new role for an old player: do B cells unleash the self-reactive CD8+ T cell
      storm necessary for the development of type 1 diabetes?
AB  - Type I diabetes mellitus is an autoimmune disease mediated by a selective immune
      mediated destruction of the insulin containing beta cells within the pancreatic
      islets of Langerhans. T cells reactive to beta cell-derived antigens are critical
      for the pathogenesis of type I diabetes, indeed treatments that target T cells
      are currently in clinical trials. CD8+ T cells may play a particularly crucial
      role in the onset of hyperglycaemia, as they can mediate beta cell destruction
      late in the pathogenesis of diabetes. However, the precise steps by which beta
      cell-reactive CD8+ T cells are activated are poorly understood. In this review we
      speculate on the possibility that B cells are essential for the activation and
      expansion of pathogenic CD8+ T cells that cause final beta cell destruction. We
      also discuss the involvement of different B cell subsets in the aetiology of
      diabetes.

PMID- 18809299
TI  - A self-reported instrument for prodromal symptoms of psychosis: testing the
      clinical validity of the PRIME Screen-Revised (PS-R) in a Japanese population.
AB  - OBJECTIVE: Early intervention for psychosis requires an easy, useful assessment
      instrument to identify subjects with prodromal symptoms at an early stage. The
      aim of this study was to test the clinical validity of the PRIME Screen-Revised
      (PS-R), a 12-item self-reported instrument for prodromal symptoms of psychosis,
      by comparing the results for a non-clinical population with those for a clinical
      population. METHOD: The PS-R was administered to 1,024 subjects (496 students and
      528 outpatients). Of the 528 patients, 115 were randomly recruited and tested
      using the Structured Interview for Prodromal Syndromes (SIPS) to determine the
      concordant validity of the PS-R. The predictive validity of the PS-R was measured
      by determining the transition rate to psychosis during a 6-month follow-up
      period. RESULTS: The specificity and sensitivity of the PS-R, using the SIPS as a
      gold standard, were 0.74 and 1.00. The concordant validity of the PS-R against
      the SIPS was 0.43. The predictive validity of the PS-R and the SIPS, defined as
      the transition rate to psychosis, were 0.11 and 0.25, respectively. None of the
      patients with negative PS-R results developed psychosis. CONCLUSIONS: Our
      findings showed that the PS-R was highly valid and that its usage is feasible in
      both general practice and clinical settings. This self-reported instrument
      represents a useful screening tool for alerting clinicians to subjects with
      psychotic prodromal symptoms.

PMID- 18809298
TI  - Temporal association of cannabis use with symptoms in individuals at clinical
      high risk for psychosis.
AB  - BACKGROUND: Cannabis use is reported to increase the risk for psychosis, but no
      prospective study has longitudinally examined drug use and symptoms concurrently
      in clinical high risk cases. METHOD: We prospectively followed for up to 2 years
      32 cases who met research criteria for prodromal psychosis to examine the
      relationship between substance use and clinical measures. RESULTS: Cases with a
      baseline history of cannabis use (41%) were older, but did not differ in clinical
      measures. Longitudinal assessments showed these cases had significantly more
      perceptual disturbances and worse functioning during epochs of increased cannabis
      use that were unexplained by concurrent use of other drugs or medications.
      CONCLUSIONS: These data demonstrate that cannabis use may be a risk factor for
      the exacerbation of subthreshold psychotic symptoms, specifically perceptual
      disturbances, in high risk cases.

PMID- 18809300
TI  - Detecting conserved coding genomic regions through signal processing of
      nucleotide substitution patterns.
AB  - OBJECTIVE: In the last few years several complete genome sequences have been made
      available to the research community. The annotation of their complete inventory
      of protein coding genes, however, has been so far an elusive goal. Classical ab
      initio gene prediction methods have been of great support for this task, but show
      notable weakness in the prediction of genes with unusual structural features. On
      the other hand, annotation on the basis of similarity to already known genes in
      other species does not permit the detection of genuinely novel genes and also
      introduces a potential source of classification error when based on similarity to
      sequences erroneously annotated as protein coding. Finally, several methods for
      the functional classification and assessment of evolutionarily conserved regions
      have been proposed, but, to our knowledge, signal processing techniques have not
      been applied yet to this problem, despite their proven usefulness at the single
      genome level. RESULTS: In this article we introduce the use of signal processing
      in comparative genomics and we propose a simple test able to evaluate the coding
      potential of a pairwise genomic sequence alignment according to the pattern and
      periodicity with which substitutions and gaps appear in the alignment. We assess
      the feasibility of our approach on an annotated set of human-mouse genomic
      alignments. CONCLUSION: Results show that the application of signal processing
      techniques to sequence alignments can be a useful tool for the identification of
      evolutionarily conserved protein-coding regions.

PMID- 18809301
TI  - Use of confirmatory factor analysis for the identification of new components of
      the metabolic syndrome: the role of plasminogen activator inhibitor-1 and
      Haemoglobin A1c.
AB  - BACKGROUND AND AIM: This study was aimed to identify additional components of
      metabolic syndrome from a set of cardiovascular risk markers. METHODS AND
      RESULTS: The homeostasis model assessment of insulin resistance (HOMA-IR), C
      reactive protein, fibrinogen, plasminogen activator inhibitor-1 (PAI-1), von
      Willebrand factor, homocysteine, Haemoglobin A1c (HbA1c), and lipoprotein(a) were
      assessed in a population-based sample of 902 nondiabetic adult subjects. Those
      biomarkers that were associated with metabolic syndrome were evaluated by
      multiple regression analysis, along with other traditional cardiovascular risk
      factors. Confirmatory factor analysis (CFA) was used to test the hypothesis that
      both the established components of metabolic syndrome and the novel variables
      identified by the regression analysis were associated with a single underlying
      factor. HOMA-IR, PAI-1 and HbA1c were the only biomarkers independently related
      to metabolic syndrome. CFA validated a one-factor model that included these
      variables. Moreover, the indices of goodness of fit were better for this expanded
      model than those obtained for a previously validated one-factor model that was
      restricted to the conventional elements of the syndrome. CONCLUSIONS: These
      findings show that PAI-1 and HbA1c are singularly linked to metabolic syndrome.
      Their elevation is presumably another manifestation of the same
      pathophysiological mechanism that underlies the recognized traits of the
      syndrome.

PMID- 18809302
TI  - Influence of age on the relation between waist circumference and cardiometabolic
      risk markers.
AB  - BACKGROUND AND AIMS: To determine whether the relation between waist
      circumference (WC) and cardiometabolic risk markers is attenuated with advancing
      age. METHODS AND RESULTS: The study population consisted of 5222 adults from the
      1999 to 2004 U.S. National Health and Nutrition Examination Survey, a nationally
      representative cross-sectional study. Study variables were assessed in a clinical
      exam. Subjects were grouped into low, moderate, and high sex-specific WC
      tertiles. The cardiometabolic risk markers examined consisted of insulin
      resistance (HOMA method), high C-reactive protein, hypertension, and high LDL
      cholesterol. Logistic regression was used to determine and compare the
      association between WC categories with high-risk cardiometabolic risk marker
      values within young (20-39 years), middle-aged (40-59 years), and older (60+
      years) adults. With few exceptions, within each of the three age categories,
      individuals with a moderate and high WC were significantly more likely to have
      elevated cardiometabolic risk markers than individuals with a low WC. There was a
      significant interaction between age and WC indicating that the relation between
      WC with insulin resistance, high CRP, and hypertension was attenuated in older
      adults. For example, the odds ratio for hypertension in those with a high
      relative to low WC was 11.07 (95% CI: 6.13-20.00) in young adults, 3.67 (2.47
      5.46) in middle-aged adults, and 2.68 (2.00-3.59) in older adults. Similar
      observations were made for BMI to those reported for WC. CONCLUSIONS: A high WC
      was associated with elevated cardiometabolic risk markers irrespective of age.
      However, the association between WC and cardiometabolic risk markers was greatly
      attenuated with advancing age.

PMID- 18809303
TI  - Furan-induced dose-response relationships for liver cytotoxicity, cell
      proliferation, and tumorigenicity (furan-induced liver tumorigenicity).
AB  - Rodent studies of furan are associated with liver cell necrosis, release of liver
      associated enzymes, increased hepatocyte proliferation, and hepatocarcinogenesis.
      For carcinogens whose proposed mode of action is cytolethality, it is
      hypothesized that the dose-response curve for tumor development would parallel
      the dose-response curve for cell death with compensatory proliferation in the
      target organ. To prospectively test this hypothesis, female B6C3F(1) mice were
      exposed to furan at carcinogenic doses and lower for 3 weeks or 2 years. At 3
      weeks and in the 2-year study, there were dose-dependent and significant
      increases in hepatic cytotoxicity at 1.0, 2.0, 4.0, and 8.0mg furan/kg. For cell
      proliferation as measured by 5-bromo-2'-deoxyuridine (BrdU) labeling index (LI),
      there was a statistically significant trend with increasing dose levels of furan
      and increased LI at 8.0mg/kg. There was an increased incidence of foci of altered
      hepatocytes, hepatocellular adenomas, and adenomas or carcinomas at 4.0 and
      8.0mg/kg and carcinomas at 8.0mg/kg. The multiplicity of microscopic tumors was
      increased and latency was decreased in mice exposed to 8.0mg/kg. Prevalence of
      hepatic nodules at necropsy was increased in mice exposed to 4.0 and 8.0mg/kg.
      Data demonstrate an association among furan-induced hepatic cytotoxicity,
      compensatory cell replication, and liver tumor formation in mice; at high doses
      >or=4.0mg/kg, furan induced hepatotoxicity, compensatory cell replication and
      tumorigenesis in a dose-related manner, while furan did not produce tumors at
      cytotoxic doses of 1.0 and 2.0mg/kg.

PMID- 18809304
TI  - An Ashbya gossypii cts2 mutant deficient in a sporulation-specific chitinase can
      be complemented by Candida albicans CHT4.
AB  - The Candida albicans genome encodes four chitinases, CHT1, CHT2, CHT3 and CHT4.
      All four C. albicans chitinase-encoding genes are non-essential. The
      corresponding proteins belong to two groups in which Cht1, Cht2 and Cht3 are more
      similar to Saccharomyces cerevisiae Cts1, while Cht4 is more similar to ScCts2.
      In the filamentous fungus Ashbya gossypii, a CTS2 homolog (ACL166w) was
      identified as the sole chitinase gene. The AgCts2 is 490 aa in Length and shows
      42.3% overall identity to ScCts2 (511 aa) and 33.2% identity to CaCht4 (388 aa).
      The A. gossypii cts2 deletion mutant showed no growth retardation or vegetative
      morphogenetic defects. However, upon sporulation Agcts2 mutants revealed a defect
      in spore formation. Expression of AgCts2 using a lacZ reporter gene was only
      found in the centre of a mycelium corresponding to the sporogenous part of a
      colony. The mutant spore phenotype of Agcts2 could be complemented by either
      AgCTS2, the S. cerevisiae CTS2, or the C. albicans CHT4 gene when expressed by
      either the AgCTS2 or the AgTEF1 promoter.

PMID- 18809305
TI  - Isolation and identification of a new hypocrellin A-producing strain Shiraia sp.
      SUPER-H168.
AB  - A new hypocrellin A-producing strain, Shiraia sp. SUPER-H168, was isolated from
      tissues of bamboo, Brachystachyum densiflorum. The morphology of this strain was
      characterized with a light microscope and a scanning electronic microscope. The
      mycelia, conidia, pycnidia of fungus were observed. Small pycnidia (10-20 microm
      in length) full of small conidia appeared on the mycelia, which were first
      reported in this study. The 18S rDNA region of this strain was amplified and
      sequenced. Then a neighbor-joining tree of 18S rDNA was constructed. According to
      the result of analysis, the strain SUPER-H168 was proved to belong to the genus
      Shiraia. Hypocrellin A was produced by solid-state fermentation, extracted by
      acetone, isolated by preparative RP-HPLC, and identified by RP-HPLC, ESI-MS and
      ultraviolet-visible absorbing scanning with diode array detection. The HA
      production could reach 2.02 mg/g dry solid substrate.

PMID- 18809306
TI  - Detection system based on the conformational change in an aptamer and its
      application to simple bound/free separation.
AB  - Aptamers are good molecular recognition elements for biosensors. Especially,
      their conformational change, which is induced by the binding to the target
      molecule, enables the development of several types of useful detection systems.
      We applied this property to bound/free separation, which is a crucial process for
      highly sensitive detection. We designed aptamers which change their conformation
      upon binding to the target molecule and thereby expose a single-strand bearing
      the complementary sequence to the capture probe immobilized onto the support. We
      named the designed aptamers "capturable aptamers" and the capture probe "capture
      DNA". Three capturable aptamers were designed based on the PrP aptamer, which
      binds to prion protein. One of these capturable aptamers was demonstrated to
      recognize prion protein and change its conformation upon binding to it. A
      detection system using this designed capturable aptamer for prion protein was
      developed. Capturable aptamers and capture DNA allow us to perform simple
      bound/free separation with only one target ligand.

PMID- 18809307
TI  - Multi-bit biomemory consisting of recombinant protein variants, azurin.
AB  - In this study a protein-based multi-bit biomemory device consisting of
      recombinant azurin with its cysteine residue modified by site-directed
      mutagenesis method has been developed. The recombinant azurin was directly
      immobilized on four different gold (Au) electrodes patterned on a single silicon
      substrate. Using cyclic voltammetry (CV), chronoamperometry (CA) and open circuit
      potential amperometry (OCPA) methods the memory function of the fabricated
      biodevice was validated. The charge transfer occurs between protein molecules and
      Au electrode enables a bi-stable electrical conductivity allowing the system to
      be used as a digital memory device. Data storage is achieved by applying redox
      potentials which are within the range of 200mV. Oxidation and open circuit
      potentials with current sensing were used for writing and reading operations
      respectively. Applying oxidation potentials in different combinations to each Au
      electrodes, multi-bit information was stored in to the azurin molecules. Finally,
      the switching robustness and reliability of the proposed device has been
      examined. The results suggest that the proposed device has a function of memory
      and can be used for the construction of nano-scale multi-bit information storage
      device.

PMID- 18809308
TI  - Area-scaling of interferometric and fluorescent detection of protein on antibody
      microarrays.
AB  - The sensitivity limits for an in-line interferometric (IL)/fluorescent (FL) dual
      channel BioCD are established as a function of spatial averaging. Forward-phase
      and sandwich assays at 10ng/ml were performed on large-scale antibody microarrays
      (6800-spot) and detected using in-line interferometry and fluorescence channels.
      The interferometric channel has an extrapolated label-free limit-of-detection
      (LOD) of 250pg/ml in a forward-phase assay for which the fluorescent channel is
      inapplicable. In the sandwich assay, the extrapolated limit-of-detection is
      70pg/ml for the interferometric channel, and for the fluorescent channel it is
      30pg/ml. Intrinsic scale-free sensitivities for the detection channels are
      defined assuming spatially uncorrelated fluctuations with sensitivities of
      S'=13pg/mm for interferometric detection and 7pg/mm for sandwich fluorescent
      detection. The intrinsic sensitivities become weakly scale dependent in the
      presence of fractal spatial correlations among the antibody spots.

PMID- 18809309
TI  - Nanotechnologic biosensor ellipsometry and biomarker pattern analysis in the
      evaluation of atherosclerotic risk profile.
AB  - A proteoheparan sulfate coated, hydrophobic silica surface serves as lipoprotein
      receptor at which the Ca(2+)-driven arteriosclerotic nanoplaque formation can be
      pursued by laser-based ellipsometry. Any lipoprotein from human blood can be very
      sensitively tested for its atherogenic properties. From the same blood sample, it
      is possible to determine the concentration and activity of a series of
      interacting biomarker molecules which, through a pattern analysis, allow to
      assess the state of health with respect to cardiovascular diseases. These two
      interlinked and complementary biosensors make a prospective cardio-cerebro
      vascular risk stratification feasible, especially the sequelae of an underlying
      arteriosclerotic disease. Based on these diagnostic tools, an optimized therapy
      decision for the patient can be taken and the necessary preventive measures for
      the still healthy person.

PMID- 18809310
TI  - High-throughput SPR sensor for food safety.
AB  - High-throughput surface plasmon resonance (SPR) biosensor for rapid and
      parallelized detection of nucleic acids identifying specific bacterial pathogens
      is reported. The biosensor consists of a high-performance SPR imaging sensor with
      polarization contrast and internal referencing (refractive index resolution 2 x
      10(-7) RIU) and an array of DNA probes microspotted on the surface of the SPR
      sensor. It is demonstrated that short sequences of nucleic acids (20-23 bases)
      characteristic for bacterial pathogens such as Brucella abortus, Escherichia
      coli, and Staphylococcus aureus can be detected at 100 pM levels. Detection of
      specific DNA or RNA sequences can be performed in less than 15 min by the
      reported SPR sensor.

PMID- 18809311
TI  - Marine diatoms as optical biosensors.
AB  - We have chemically modified the frustules of the marine diatom Coscinodiscus
      concinnus Wm. Smith to properly bind a highly selective bioprobe such as an
      antibody. By measuring the changes in the photoluminescence emission of diatoms
      frustules, we have monitored the molecular recognition event between the antibody
      and its ligand: the dissociation constant estimated is of the same order of that
      measured by standard Biacore. The nanostructured silica frustules, a low-cost and
      natural available material, have shown high sensitivity, equal to 1.2+/-0.2 nm
      microM(-1), and a detection limit of 100 nM, and thus are quite ideal candidates
      for lab-on-particle applications.

PMID- 18809312
TI  - Patient migration, access to expertise and optimal patterns of care.

PMID- 18809313
TI  - Complementary and alternative treatment methods in children with cancer: A
      population-based retrospective survey on the prevalence of use in Germany.
AB  - INTRODUCTION: Few studies have been conducted to date on the prevalence of use of
      complementary and alternative treatment methods (CAMs) in paediatric oncology,
      and those that have been conducted are often not representative. We therefore
      decided to study a representative sample of children with cancer in the German
      population. PATIENTS AND METHODS: The study took the form of a retrospective
      survey amongst all parents whose children were first diagnosed with a disease
      covered by the German Childhood Cancer Registry in 2001. The primary objectives
      of the survey were to establish the prevalence of use of CAM and the factors
      related to its use. RESULTS: Of the 1595 questionnaires sent out, 1063 (67%)
      could be evaluated. 35% of the responders had used CAM. The most frequently used
      methods were homeopathy, dietary supplements and anthroposophic medicine
      including mistletoe therapy. Factors which increased the probability of using CAM
      were the previous use of CAM, higher social status and poor prognosis of the
      child's disease. The most frequently named reasons for use of CAM were physical
      stabilisation, strengthening the immune system and improving the chance of cure.
      Whilst the sources of information about CAM were in most cases not doctors, 71%
      of users had nevertheless spoken to a doctor about using CAM. The effects of the
      CAM perceived by the parents were for the most part positive. 89% of the users
      reported that they would recommend CAM to other parents. CONCLUSIONS: CAMs are
      administered alongside standard therapy to 35% of children with cancer in
      Germany, usually by the parents. Prospective studies on the effects and side
      effects of the most frequently used methods are urgently needed, and paediatric
      oncologists should have sufficient knowledge of CAM to enable them to advise
      parents professionally and competently about these treatments, too.

PMID- 18809314
TI  - An EORTC phase I study of Bortezomib in combination with oxaliplatin, leucovorin
      and 5-fluorouracil in patients with advanced colorectal cancer.
AB  - The combination of oxaliplatin, leucovorin and 5-fluorouracil (FOLFOX-4) is still
      a reference regimen in advanced colorectal cancer; however, the addition of new
      biologic compounds represents a significant way forward. Bortezomib is an
      inhibitor of proteasome, a multicatalytic enzyme complex that degrades several
      intracellular proteins. In this study, escalating doses of Bortezomib were
      administered along with the standard FOLFOX-4 doses, in order to evaluate the
      dose-limiting toxicity (DLT), toxicity profile and activity of the combination.
      Patients with advanced colorectal cancer, unpretreated for metastatic disease,
      were enroled in the study. Bortezomib starting dose was 1.3mg/m(2), which was to
      be escalated in the subsequent steps according to the toxicities observed after
      first cycle. Exploratory pharmacogenetics research was conducted by analysing the
      association between clinical outcomes and polymorphisms in candidate genes for
      response to each of the used drugs. Correlation between tumour marker changes and
      response was also investigated. One mg/m(2) (DL-1) was defined as being the
      maximum tolerated dose since only 1 DLT was observed in 6 patients. The main
      toxicities were haematologic, neuropathy, diarrhoea and fatigue. Amongst 13
      evaluable patients, five had a partial response, five had a stable disease and
      three patients progressed. Two patients are long-term survivors after a combined
      chemosurgical approach. Further trials of the current combination may be
      justified.

PMID- 18809315
TI  - Biosorptive removal of arsenic from drinking water.
AB  - A biomass derived from the plant Momordica charantia has been found to be very
      efficient in arsenic(III) adsorption. An attempt was made to use this biomass for
      arsenic(III) removal under different conditions. The parameters optimized were
      contact time (5-150 min), pH (2-11), concentration of adsorbent (1-50 g/l),
      concentration of adsorbate (0.1-100mg/l), etc. It was observed that the pH had a
      strong effect on biosorption capacity. The optimum pH obtained for arsenic
      adsorption was 9. The influence of common ions such as Ca(2+), Mg(2+), Cd(2+),
      Se(4+), Cl(-), SO(4)(2-), and HCO(3)(-), at concentrations varying from 5 to 1000
      mg/l was investigated. To establish the most appropriate correlation for the
      equilibrium curves, isotherm studies were performed for As(III) ion using
      Freundlich and Langmuir adsorption isotherms. The pattern of adsorption fitted
      well with both models. The biomass of M. charantia was found to be effective for
      the removal of As(III) with 88% sorption efficiency at a concentration of 0.5mg/l
      of As(III) solution, and thus uptake capacity is 0.88 mg As(III)/gm of biomass.
      It appears that this biomass should be used as a palliative food item. Further it
      also appears that the dietary habits may play a role in the toxic effects of
      ingested arsenic.

PMID- 18809316
TI  - Fixed-bed adsorption performance of oil palm shell-based activated carbon for
      removal of 2,4,6-trichlorophenol.
AB  - This study investigated the adsorption potential of oil palm shell-based
      activated carbon to remove 2,4,6-trichlorophenol from aqueous solution using
      fixed-bed adsorption column. The effects of 2,4,6-trichlorophenol inlet
      concentration, feed flow rate and activated carbon bed height on the breakthrough
      characteristics of the adsorption system were determined. The regeneration
      efficiency of the oil palm shell-based activated carbon was evaluated using
      ethanol desorption technique. Through ethanol desorption, 96.25% of the
      adsorption sites could be recovered from the regenerated activated carbon.

PMID- 18809317
TI  - Modeling the discoloration of a mixture of reactive textile dyes by commercial
      laccase.
AB  - Degradation of a mixture of three reactive textile dyes (Reactive Black 5,
      Reactive Yellow 15 and Reactive Red 239), simulating a real textile effluent, by
      commercial laccase, was investigated in a batch reactor. The discoloration was
      appraised as a percentage of the absorbance reduction at the wavelength of
      maximum absorbance for each dye and as total color removal based in all visible
      spectrum. A significantly high discoloration was achieved in both cases,
      indicating the applicability of this method for textile wastewater treatment.
      Mathematical models were developed to simulate the kinetics of laccase catalyzed
      degradation of reactive dyes in mixtures. Like in single dye degradation, some of
      the reactions present an unusual kinetic behavior, corresponding to the
      activation of the laccase-mediator system. The kinetic constants of the models
      were estimated by minimizing the difference between the predicted and the
      experimental time courses. Although not perfect, the ability of the models in
      representing the experimental results suggests that they could be used in design
      and simulation applications.

PMID- 18809318
TI  - Agar from Gracilaria gracilis (Gracilariales, Rhodophyta) of the Patagonic coast
      of Argentina--content, structure and physical properties.
AB  - Milled summer thalli of Gracilaria gracilis from Argentina were sequentially
      extracted with water at room temperature (RTW1-3), 70 degrees C (W701-3) and 90
      degrees C (W901-2). Both W701 and W901 consisted of high molecular weight
      polysaccharides (ca. 540,000Da), but polydispersity was higher for the major
      product W701 (yield, 72% of the recovered). Structural analyzes by methylation
      and (13)C NMR spectroscopy revealed that W701 was mainly agarose. Alkaline
      treatment, together with structural analyzes, indicated a negligible proportion
      of precursor l-galactose 6-sulfate residues in this product, while they were
      clearly detected in the (13)C NMR spectra of RTW2-3. The presence of floridean
      starch in W901 had an antagonistic effect on its gel strength, which resulted
      nearly three times lower than that of fraction W701. Ultrastructural observation
      by transmission electron microscopy showed that, after extraction with hot water,
      a partial loss of cell wall stratification and disorganization of the cuticle had
      occurred. Final cellular debris exhibited swelling in the microfibrillar
      component. After this first thorough study of the chemical composition and
      physical properties of the products of G. gracilis from Bahia Bustamante we
      conclude that a good quality agarose is obtained in high yield after extraction
      with water at 70 degrees C without the requirement of alkaline pretreatment,
      which usually produces degradation of the polysaccharide.

PMID- 18809319
TI  - Assessing the addition of mineral processing waste to green waste-derived
      compost: an agronomic, environmental and economic appraisal.
AB  - The overall aim of this study was to evaluate the benefit of mixing two large
      volume wastes, namely mineral processing waste and source-segregated green waste
      compost, on the growth performance of plants targeted towards high
      (horticulture/agriculture) and low (amenity/restoration) value markets. The
      secondary aims were to evaluate the influence of mineral waste type on plant
      growth performance and to undertake a simple economic analysis of the use of
      mineral-compost mixtures in land restoration. Our results showed that in
      comparison to organic wastes, mineral wastes contained a low available nutrient
      content which reduces compost quality. This is supported by growth trials with
      tomato, wheat and grass which showed that, irrespective of mineral source, plants
      performed poorly in compost blended with mineral waste in comparison to those
      grown in green waste or peat-based compost alone. In terms of consumer
      confidence, unlike other wastes (e.g. biosolids and construction/demolition
      waste) the mineral quarry wastes can be expected to be free of potentially toxic
      elements, however, the production costs of compost-mineral waste mixtures and
      subsequent transport costs may limit its widespread use. In addition, handling of
      the material can be difficult under wet conditions and effective blending may
      require the purchase of specialist equipment. From our results, we conclude that
      mineral fines may prove useful for low quality, low value landscaping activities
      close to the source of production but are unsuited to high value markets.

PMID- 18809320
TI  - Potentiality of lignin from the Kraft pulping process for removal of trace nickel
      from wastewater: effect of demineralisation.
AB  - An industrial raw Kraft lignin was investigated to ascertain its potential use
      for removal of trace Ni(II) ion from wastewater by using dilute solutions (0.34
      1.7 mM) as models. The effect of demineralisation on its metal sorption ability
      was examined by employing acid pre-treated samples. Under fixed pre-established
      equilibrium conditions, the raw lignin exhibited a lower effectiveness than the
      demineralised one, with the latter attaining an almost complete removal of Ni(II)
      ions. For both lignins, sorption kinetics was properly described by a pseudo
      second order rate model. Equilibrium isotherms were also determined and
      adequately represented by conventional two-parameter models. The higher nickel
      sorption capacity for the demineralised lignin compared to the raw sample was
      consistent with enhancements in the negative magnitude of zeta potential, sodium
      sorption capacity, and content of phenolic hydroxyl groups occasioned by the acid
      pre-treatment. Accordingly, demineralisation appears as a readily convenient
      strategy to improve the behaviour of industrial Kraft lignin for potential use as
      a biosorbent of trace nickel from polluted water.

PMID- 18809321
TI  - TCF bleaching of soda-anthraquinone and diethanolamine pulp from oil palm empty
      fruit bunches.
AB  - The AOpAZRP bleaching sequence (A is an acid treatment, Op an oxygen and peroxide
      stage, Z an ozone stage, R a reductive treatment and P a peroxide stage) have
      been applied to oil palm empty fruit bunches (EFB) soda-anthraquinone and
      diethanolamine pulp. On similar Kappa numbers for the two types of pulp (14.2 and
      17.3), paper from unbleached soda-anthraquinone pulp exhibited increased tensile
      index (25.8 Nm/g), stretch (2.35%), burst index (1.69 kN/g), tear index (0.50 mN
      m(2)/g) and brightness (60.6%) relative to paper for unbleached diethanolamine
      pulp; but the latter type of pulp exhibited higher viscosity (659 mL/g) than the
      former. Upon bleaching with the AOpAZRP sequence, diethanolamine pulp exhibited
      higher viscosity (783 mL/g), and the properties of the paper sheets were close to
      or even better to those from soda-anthraquinone pulp, namely: 22.2 vs 20.4 Nm/g
      tensile index, 1.30 vs 1.42 kN/g burst index, 0.71 vs 0.70 mN m(2)/g tear index
      and 71.3% vs 77.5% brightness. Therefore, the properties of paper from
      diethanolamine pulp evolved more favourably during bleaching than did those of
      paper from soda-anthraquinone pulp.

PMID- 18809322
TI  - Effect of ammonia concentration on fermentative hydrogen production by mixed
      cultures.
AB  - The effect of ammonia concentration ranging from 0 to 10 g N/L on fermentative
      hydrogen production by mixed cultures was investigated in batch tests using
      glucose as substrate at 35 degrees C and initial pH 7.0. The experimental results
      showed that during the fermentative hydrogen production, the substrate
      degradation efficiency increased with increasing ammonia concentration from 0 to
      0.01 g N/L. The hydrogen production potential, hydrogen yield and average
      hydrogen production rate increased with increasing ammonia concentration from 0
      to 0.1g N/L. The maximum hydrogen production potential of 291.4 mL, maximum
      hydrogen yield of 298.8 mL/g glucose and maximum average hydrogen production rate
      of 8.5 mL/h were all obtained at the ammonia concentration of 0.1g N/L.

PMID- 18809323
TI  - Biodiesel production by in situ transesterification of municipal primary and
      secondary sludges.
AB  - The potential of using municipal wastewater sludges as a lipid feedstock for
      biodiesel production was investigated. Primary and secondary sludge samples
      obtained from a municipal wastewater treatment plant in Tuscaloosa, AL were
      freeze-dried and subjected to an acid-catalyzed insitu transesterification
      process. Experiments were conducted to determine the effects of temperature,
      sulfuric acid concentration, and mass ratio of methanol to sludge on the yield of
      fatty acid methyl esters (FAMEs). Results indicated a significant interactive
      effect between temperature, acid concentration, and methanol to sludge mass ratio
      on the FAME yield for the insitu transesterification of primary sludge, while the
      FAME yield for secondary sludge was significantly affected by the independent
      effects of the three factors investigated. The maximum FAME yields were obtained
      at 75 degrees C, 5% (v/v) H(2)SO(4), and 12:1 methanol to sludge mass ratio and
      were 14.5% and 2.5% for primary and secondary sludge, respectively. Gas
      chromatography (GC) analysis of the FAMEs revealed a similar fatty acid
      composition for both primary and secondary sludge. An economic analysis estimated
      the cost of $3.23/gallon for a neat biodiesel obtained from this process at an
      assumed yield of 10% FAMEs/dry weight of sludge.

PMID- 18809324
TI  - Membrane-bound 'synthetic lipase' specifically cultured under solid-state
      fermentation and submerged fermentation by Rhizopus chinensis: a comparative
      investigation.
AB  - Rhizopus chinensis was able to produce synthetic lipases under both solid-state
      and submerged fermentations. These lipases were extracted from cell membrane
      using Triton X-100, and purified to homogeneity through ammonium sulfate
      precipitation, hydrophobic interaction chromatography and gel filtration
      chromatography. Judging from SDS-PAGE, the specific synthetic lipases associated
      with SSF (named as SSL) and SmF (named as SML) were different in the apparent
      molecular mass (62 and 40kDa). In term of hydrolytic activity, both enzymes
      exhibited maximum values at pH 8.0 and 40 degrees C; SSL appeared to be more pH
      tolerant and thermostable than SML. PMSF negligibly affected SSL but strongly
      reduced the activity of SML. Both enzymes showed clear preference for long
      chained p-nitrophenyl esters, yielding maximum activity towards p-nitrophenyl
      palmitate (with SSL) and p-nitrophenyl laurate (with SML). In term of synthetic
      activity, lyophilized enzymes gave the highest values both at 30 degrees C, but
      at different pH memories (7.5 for SSL and 6.5 for SML). Most of ethyl esters
      synthesized by the two enzymes achieved good yields (>90%), and tetradecanoic
      acid and laurate acid separately served as the best acyl donors.

PMID- 18809325
TI  - Analogues of 2-phenyl-ethenesulfonic acid phenyl ester have dual functions of
      inhibiting expression of inducible nitric oxide synthase and activating
      peroxisome proliferator-activated receptor gamma.
AB  - We identified a series of 2-phenyl-ethenesulfonic acid phenyl ester analogues as
      novel dual-function agents that suppressed nitric oxide production in
      lipopolysaccharide/interferon gamma-stimulated RAW264.7 cells and activated
      peroxisome proliferator-activated receptor gamma (PPARgamma) in a cell-based
      transactivation assay. Western blot analysis demonstrated that these compounds
      inhibit the expression of inducible nitric oxide synthase protein, and
      scintillation proximity assay validated their ability to bind to PPARgamma. Our
      studies provide the basis for developing these dual-function agents for anti
      inflammation and anti-atherosclerosis therapy.

PMID- 18809326
TI  - Small, non-peptide C5a receptor antagonists: part 1.
AB  - The optimisation of a series of amides for C5a receptor binding and functional
      activity, and physicochemical properties is described. The initial hit, 1 (IC(50)
      1 microM), was discovered during high throughput screening, from which highly
      potent C5a receptor antagonists (e.g.14, IC(50) 5 nM) were developed.

PMID- 18809327
TI  - Design and synthesis of 6-phenylnicotinamide derivatives as antagonists of TRPV1.
AB  - 6-Phenylnicotinamide (2) was previously identified as a potent TRPV1 antagonist
      with activity in an in vivo model of inflammatory pain. Optimization of this lead
      through modification of both the biaryl and heteroaryl components has resulted in
      the discovery of 6-(4-fluorophenyl)-2-methyl-N-(2-methylbenzothiazol-5
      yl)nicotinamide (32; SB-782443) which possesses an excellent overall profile and
      has been progressed into pre-clinical development.

PMID- 18809328
TI  - Optimization of a series of potent and selective ketone histone deacetylase
      inhibitors.
AB  - Histone deacetylase (HDAC) inhibitors offer a promising strategy for cancer
      therapy and the first generation HDAC inhibitors are currently in the clinic.
      Herein we describe the optimization of a series of ketone small molecule HDAC
      inhibitors leading to potent and selective class I HDAC inhibitors with good dog
      PK.

PMID- 18809329
TI  - Microwave-assisted synthesis of unnatural amino acids.
AB  - Microwave irradiation has been proven to be a useful tool in the rapid assembly
      of racemic unnatural amino acids in only two steps. Additional benefits of this
      methodology are the commercial availability of the inexpensive starting materials
      and the high yields and high purities of the final amino acid products.

PMID- 18809330
TI  - The effects of a motor and a cognitive concurrent task on walking in children
      with developmental coordination disorder.
AB  - The effects of type (cognitive vs. motor) and difficulty level (easy vs. hard) of
      a concurrent task on walking were examined in 10 boys and 4 girls (age 4-6 years)
      with developmental coordination disorder (DCD) and 28 age- and gender-matched
      unaffected children. Each child performed free walking (single task), walking
      while carrying an empty tray (dual task, the concurrent task being motor and
      easy), walking while carrying a tray with 7 marbles (the concurrent task being
      motor and hard), walking while repeating a series of digits forward (the
      concurrent task being cognitive and easy), and walking while repeating the digits
      backward (the concurrent task being cognitive and hard). Walking was affected by
      the concurrent task (i.e., dual-task cost) in the children with DCD more so than
      in the comparison children. Greater task difficulty also increased the dual-task
      cost in the children with DCD more so than in the comparison children. These
      patterns were only noted for the motor concurrent task. The cognitive concurrent
      task also affected walking, but the dual-task costs did not differ between
      difficulty levels, nor between the groups.

PMID- 18809331
TI  - HIF-1 regulation: not so easy come, easy go.
AB  - The hypoxia-inducible factor-1 (HIF-1) is the master regulator of the cellular
      response to hypoxia and its expression levels are tightly controlled through
      synthesis and degradation. It is widely accepted that HIF-1alpha protein
      accumulation during hypoxia results from inhibition of its oxygen-dependent
      degradation by the von Hippel Lindau protein (pVHL) pathway. However, recent data
      describe new pVHL- or oxygen-independent mechanisms for HIF-1alpha degradation.
      Furthermore, the hypoxia-induced increase in HIF-1alpha levels is facilitated by
      the continued translation of HIF-1alpha during hypoxia despite the global
      inhibition of protein translation. Recent work has contributed to an increased
      understanding of the mechanisms that control the translation and degradation of
      HIF-1alpha under both normoxic and hypoxic conditions.

PMID- 18809332
TI  - Novel insights into GPCR-peptide interactions: mutations in extracellular loop 1,
      ligand backbone methylations and molecular modeling of neurotensin receptor 1.
AB  - Investigating prototypical interactions between NT(8-13) and the human
      neurotensin receptor 1 (hNTR1), we created a receptor-ligand model that was
      validated by site-directed mutagenesis and structure-activity relationship
      studies. Stabilization of the extracellular loop 1 (EL1) by pi-stacking clusters
      proved to be important for agonist binding when substitution of six conserved
      amino acids by alanine resulted in an agonist specific loss of maximal binding
      capacity. In agreement with our modeling studies, EL1 seems to adopt a clamp-type
      border area controlling the shape of the binding site crevice. Employing
      chemically manipulated peptide analogs as molecular probes, the impact of
      backbone modifications on receptor-ligand interaction, especially the influence
      on ligand conformation, was examined in binding studies and explained by in
      silico analysis.

PMID- 18809333
TI  - Mycophenolic acid analogs with a modified metabolic profile.
AB  - Mycophenolic acid (MPA), a clinically used immunosuppressant, is extensively
      metabolized into an inactive C7-glucuronide and removed from circulation. To
      circumvent the metabolic liability imposed by the C7-hydroxyl group, we have
      designed a series of hybrid MPA analogs based on the pharmacophores present in
      MPA and new generations of inosine monophosphate dehydrogenase (IMPDH)
      inhibitors. The synthesis of MPA analogs has been accomplished by an allylic
      substitution of a common lactone. Biological evaluations of these analogs and a
      preliminary structure-activity relationship (SAR) are presented.

PMID- 18809334
TI  - Structure-activity relationships of 1,4-dihydropyridines that act as enhancers of
      the vanilloid receptor 1 (TRPV1).
AB  - Vanilloid agonists such as capsaicin activate ion flux through the TRPV1 channel,
      a heat- and ligand-gated cation channel that transduces painful chemical or
      thermal stimuli applied to peripheral nerve endings in skin or deep tissues. We
      have probed the SAR of a variety of 1,4-dihydropyridine (DHP) derivatives as
      novel 'enhancers' of TRPV1 activity by examining changes in capsaicin-induced
      elevations in (45)Ca(2+)-uptake in either cells ectopically expressing TRPV1 or
      in cultured dorsal root ganglion (DRG) neurons. The enhancers increased the
      maximal capsaicin effect on (45)Ca(2+)-uptake by typically 2- to 3-fold without
      producing an action when used alone. The DHP enhancers contained 6-aryl
      substitution and small alkyl groups at the 1 and 4 positions, and a 3
      phenylalkylthioester was tolerated. Levels of free intracellular Ca(2+), as
      measured by calcium imaging, were also increased in DRG neurons when exposed to
      the combination of capsaicin and the most efficacious enhancer 23 compared to
      capsaicin alone. Thus, DHPs can modulate TRPV1 channels in a positive fashion.

PMID- 18809335
TI  - TGF-beta1 genotypes in cirrhosis: relationship with the occurrence of liver
      cancer.
AB  - This study aimed to verify whether specific single nucleotide polymorphisms
      (SNPs) of the transforming growth factor-beta1 (TGF-beta1) may predispose to end
      stage liver disease and/or hepatocellular carcinoma (HCC). One hundred eighty
      eight consecutive patients transplanted for liver cirrhosis (HBV N=21, HCV N=68,
      alcoholic N=55 and others N=23) and a control group of 140 healthy blood donors
      were investigated. Four SNPs were studied by restriction fragment length assays: 
      800G>A, -509C>T, Leu10Pro and Arg25Pro. Patients were found to possess the -509T/
      * (TT 53/188, CT 85/188, CC 50/188 vs TT 22/140, CT 61/140, CC 57/140; p<0.002)
      and Arg25Pro C/ * genotypes (CC 1/188, CG 31/188, GG 156/188 vs CC 0/140, CG
      13/140, GG 127/140; p<0.05) more frequently than controls. Patients with
      cirrhosis complicated by HCC possessed more frequently the Leu10Pro T/ * genotype
      than patients without HCC (TT 20/54, CT 26/54, CC 8/54 vs TT 31/134, CT 69/134,
      CC 34/134; p<0.05). The analysis of molecular variance detected significant
      genotypic differentiations between controls and cirrhotics but not between
      cirrhotics with or without HCC. In conclusion, TGF-beta1 SNPs probably facilitate
      the development of liver cirrhosis, while they seem to have a limited role in
      predicting the occurrence of HCC.

PMID- 18809336
TI  - Constitutive expression of CXCL14 in healthy human and murine epithelial tissues.
AB  - CXCL14 (BRAK) is an ill-described chemokine with unknown receptor selectivity.
      The human chemokine is constitutively expressed in epithelial tissues and is
      selective for dendritic cell precursors, indicating a possible function in the
      maintenance of epithelial DCs. Several studies have addressed the question of
      human CXCL14 expression in cancerous tissues; however, distribution in healthy
      tissues and, in particular, the cellular origin of this chemokine has not been
      thoroughly investigated. The expression pattern of murine CXCL14 is largely
      unknown. In agreement with the human chemokine, we demonstrated ubiquitous and
      constitutive expression of murine CXCL14 in various tissues, foremost in those of
      epithelial origin such as the skin and the gastrointestinal tract. In addition,
      we did not find any CXCL14 in lymphoid tissues. Interestingly and in contrast to
      humans, murine CXCL14 was strongly expressed in the lung. In the skin, CXCL14 was
      produced by keratinocytes and dermal macrophages in both mice and humans, whereas
      CXCL14-expressing mast cells could only be found in the human dermis. Therefore,
      despite the remarkable structural homology and the broad similarity in the tissue
      distribution of human and murine CXCL14, distinct differences point to diverse,
      species-specific needs for CXCL14 in epithelial immunity.

PMID- 18809337
TI  - The distribution of interleukin-19 in healthy and neoplastic tissue.
AB  - The influence of interleukin (IL)-19, a recently discovered cytokine in the IL-10
      family, on tissue is still unclear. Our aim was to determine the distribution of
      IL-19 expression and to delineate the cell types that express IL-19 in healthy
      and neoplastic tissue, because this information will significantly facilitate the
      exploration of its pathophysiological functions. We used tissue microarray
      technology and an immunohistochemical survey with an anti-IL-19 monoclonal
      antibody to examine the expression of IL-19 in 28 healthy and 15 neoplastic
      tissues. IL-19 protein was positively stained in 15 healthy tissue types and
      three major cell types: epithelial cells, endothelial cells, and macrophages. We
      also found that several types of tumor cells were positively stained for IL-19,
      especially in squamous cell carcinoma (SCC) of the skin, tongue, esophagus, and
      lung. SCC of the oral cavity expressed IL-19 mRNA and its receptors. In two cell
      lines derived from SCC of oral cavity tumor tissue, IL-19 specifically activated
      an intracellular signal and induced proliferation of the cells, which indicated
      that IL-19 may act in an autocrine manner in SCC tumors. This study provides
      important references for further investigation of the biological functions and
      clinical implications of IL-19 in humans.

PMID- 18809339
TI  - The triangular future of epidemiology.

PMID- 18809338
TI  - From the diet to the nucleus: vitamin A and TGF-beta join efforts at the mucosal
      interface of the intestine.
AB  - The vitamin A metabolites, including retinoic acid (RA), form ligands for
      retinoic acid-related nuclear receptors and together they play pleiotropic roles
      in various biological processes. Recently, we described that RA also functions as
      a key modulator of transforming growth factor-beta (TGF-beta)-driven immune
      deviation, capable of suppressing the differentiation of interleukin-17 secreting
      T helper cells (T(H)17) and conversely promoting the generation of Foxp3(+) T
      regulatory (Treg) cells. This review will focus on the role of RA in the
      reciprocal TGF-beta-driven differentiation of T(H)17 and Treg and on the
      importance of such regulatory mechanism to control a functional immune system, in
      particular at the mucosal interface of the intestine.

PMID- 18809340
TI  - The association between physical activity and osteoporotic fractures: a review of
      the evidence and implications for future research.
AB  - PURPOSE: Physical activity helps maintain mobility, physical functioning, bone
      mineral density (BMD), muscle strength, balance and, therefore, may help prevent
      falls and fractures among the elderly. Meanwhile, it is theoretically possible
      that physical activity increases risk of fractures as it may increase risk of
      falls and has only a modest effect on BMD. This review aims to assess the
      potential causal association between physical activity and osteoporotic fractures
      from an epidemiological viewpoint. METHODS: As the medical literature lacks
      direct evidence from randomized controlled trials (RCTs) with fracture end
      points, a meta-analysis of 13 prospective cohort studies with hip fracture end
      point is presented. The current evidence base regarding the link between exercise
      and fracture risk determinants (namely, falls, BMD, and bone quality) are also
      summarized. RESULTS: Moderate-to-vigorous physical activity is associated with a
      hip fracture risk reduction of 45% (95% CI, 31-56%) and 38% (95% CI, 31-44%),
      respectively, among men and women. Risk of falling is suggested to be generally
      reduced among physically active people with a potential increased risk in the
      most active and inactive people. Positive effects of physical activity on BMD and
      bone quality are of a questionable magnitude for reduction of fracture risk.
      CONCLUSION: The complexity of relationship between physical activity and
      osteoporotic fractures points out to the need for RCTs to be conducted with
      fractures as the primary end point.

PMID- 18809341
TI  - Metabolic syndrome--the impact of depression.

PMID- 18809342
TI  - Low bone mineral density and mortality in men and women: the Third National
      Health and Nutrition Examination Survey linked mortality file.
AB  - PURPOSE: The aim of this study is to determine the association of bone mineral
      density and mortality over a median follow-up of 9 years. METHODS: The baseline
      data used are from the Third National Health and Nutrition Examination Survey
      (NHANES III), a nationally representative sample of non-institutionalized
      civilians. A cohort of 5,769 non-Hispanic whites, non-Hispanic blacks, and
      Mexican Americans aged 50 years and older at baseline (1988-1994) was followed
      through 2000 for overall mortality using the restricted-use NHANES III Linked
      Mortality File (1,741 deaths). Total proximal femoral bone mineral density was
      measured by dual-energy x-ray absorptiometry and categorized into quartiles. Cox
      proportional hazards models were used to estimate the relative risk of death
      after adjusting for multiple risk factors. RESULTS: Compared with subjects in the
      highest quartile of bone mineral density, those in the lowest quartile had
      greater risk of death (relative risk, 1.53; 95% confidence interval: 1.08-2.18;
      P=0.02). There was no significant interaction of bone mineral density with race
      or ethnicity. CONCLUSION: Low bone mineral density was associated with increased
      risk of death.

PMID- 18809343
TI  - Longitudinal changes in triglycerides according to ANGPTL4[E40K] genotype and
      longitudinal body weight change in the atherosclerosis risk in communities study.
AB  - PURPOSE: Allelic variation in the adipokine angiopoietin-like 4 gene
      (ANGPTL4[E40K]) has been cross-sectionally associated with triglycerides, but the
      effects of genotype, or the interaction between genotype and body weight, on
      longitudinal triglyceride change have not been studied. METHODS: Body weight,
      triglycerides, and ANGPTL4[E40K] genotype were determined at baseline (1987-1989)
      and at 3 follow-up exams (1990-1992, 1993-1995, 1996-1998) in 7,939 white
      ANGPTL4[E40K] G allele homozygotes and 344 A allele carriers. Changes in body
      weight and triglycerides were characterized as the difference between exam 4 and
      baseline measurements. RESULTS: ANGPTL4[E40K] A allele carriers had triglyceride
      concentrations that were 15 to 18 mg/dL lower than G allele homozygotes at all
      exams (P<0.0001). Triglycerides increased in both genotype groups over the 9-year
      period (+19.1+/-0.9 and +16.2+/-4.1 mg/dL in GG and GA/AA, respectively; P
      difference, 0.48). Weight gain was associated with increased triglycerides to a
      comparable degree in both genotype groups (+5.5+/-0.3 and +4.3+/-0.9 mg/dL per 2
      kg increase in body weight in GG and GA/AA, respectively, p interaction=0.30).
      CONCLUSIONS: Differences in triglyceride concentrations between ANGPTL4[E40K] A
      allele carriers and G allele homozygotes are maintained over time, but the degree
      of increase in triglycerides was similar between groups and was not modified by
      body weight changes.

PMID- 18809344
TI  - Evidence to suggest that cathepsin K degrades articular cartilage in naturally
      occurring equine osteoarthritis.
AB  - OBJECTIVE: The mechanisms leading to degeneration of articular cartilage in
      osteoarthritis (OA) are complex and not yet fully understood. Cathepsin K (CK) is
      a cysteine protease which can also cleave the triple helix of type II collagen.
      This exposes a neoepitope that can now be identified by specific antibodies. The
      aim of this study was to obtain evidence suggesting a role for CK in naturally
      occurring equine OA in both lesional and peri-lesional regions. METHODS:
      Articular cartilages (n=12 horses; 5 healthy, 7 OA) were harvested from animals
      postmortem. A gross macroscopic examination, histologic (Safranin O-Fast Green
      and Picrosirius red staining) and immunohistochemical evaluation were performed.
      Samples were divided into normal appearing cartilage, peri-lesional and lesional
      cartilage. Cartilage degradation in the samples was graded histologically and
      immunohistochemically. CK and possible CK cleavage were detected
      immunohistochemically with specific anti-protein and anti-neoepitope antibodies,
      respectively. A comparison of CK neoepitope (C2K) production with the collagenase
      generated neoepitope produced by matrix metalloproteinases (MMP)-1, 8 and 13
      (C2C) was also assessed immunohistochemically. RESULTS: CK and CK cleavage were
      significantly more abundant in OA cartilage (both peri-lesional and lesional)
      when compared to remote cartilage within the sample joint or cartilage from
      healthy joints. The immunohistochemical pattern observed for CK degradation (C2K)
      was similar to that of collagenase degradation (C2C). Macroscopic cartilage
      changes and histologic findings were significantly correlated with
      immunohistochemistry results. CONCLUSION: The data generated suggests that CK may
      be involved in cartilage collagen degradation in naturally occurring
      osteoarthritis.

PMID- 18809345
TI  - Extensive NMRD studies of Ni(II) salt solutions in water and water-glycerol
      mixtures.
AB  - Aqueous solutions of simple nickel(II) salts are a classical test case for
      theories of the paramagnetic relaxation enhancement (PRE) and its dependence on
      the magnetic field (nuclear magnetic relaxation dispersion, NMRD), going back to
      late fifties. We present here new experimental data, extending the NMRD range up
      to 21T (900 MHz). In addition to salt solutions in (acidified) water, we have
      also measured on solutions containing glycerol. The aqueous solution data do not
      show any significant changes compared to the earlier experiments. The
      interpretation, based on the general ("slow-motion") theory is also similar to
      the earlier work from our laboratory. The NMRD-data in mixed solvents are
      qualitatively different, indicating that the glycerol not only changes the
      solution viscosity, but may also enter the first coordination sphere of the metal
      ion, resulting in lower symmetry complexes, characterized by non-vanishing
      averaged zero-field splitting. This hypothesis is corroborated by molecular
      dynamics simulations. A strategy appropriate for interpreting the NMRD-data for
      the chemically complicated systems of this type is proposed.

PMID- 18809346
TI  - The effect of peritoneal dialysate on DXA bone densitometry results in patients
      with end-stage renal disease.
AB  - The bone mineral density of patients undergoing peritoneal dialysis (PD) is low
      compared to a healthy population. No studies have been conducted to investigate
      whether the presence of peritoneal dialysate affects dual-energy X-ray
      absorptiometry (DXA) results. We hypothesized that the presence of peritoneal
      dialysate would not affect the measurement of bone mineral density (BMD) or bone
      mineral content (BMC) in the spine. Thirty patients on PD had DXA scans of the
      lumbar spine and hip completed before and after the drainage of peritoneal
      dialysate. A paired t-test was used to compare the difference in area, BMC, and
      BMD before and after drainage of dialysate. A significant difference was found in
      the BMC of the spine before and after the drainage of dialyzate. We recommend
      that peritoneal dialyzate be removed prior to scanning patients on PD and that
      densitometry technologists should be observant about the presence of peritoneal
      dialysate.

PMID- 18809347
TI  - Expression of ghrelin receptor, GHSR-1a, and its functional role in the porcine
      ovarian follicles.
AB  - Recently, we reported stimulatory effect of ghrelin alone and in combination with
      growth hormone (GH) on estradiol secretion, aromatase activity in parallel with
      inhibitory effect on cell apoptosis. The aim of this study was to analyze the
      expression of the functional ghrelin receptor (GHS-R type 1a) and the effect of
      GH on GHSR-1a expression in cultured whole porcine follicles. Using RT-PCR and
      Western Blots, we demonstrated the presence of GHSR-1a in prepubertal pig ovary
      and found no influence of GH on either GHSR-1a protein levels or mRNA expression.
      Additionally, to show if, noted previously by us action of ghrelin on ovarian
      follicular function is dependent of its binding to GHSR-1a, we used an antagonist
      of the ghrelin receptor, (D-Lys-3)-GHRP-6. In cultures treated together ghrelin
      and (D-Lys-3)-GHRP-6, estradiol secretion, aromatase activity and cell
      proliferation returned to control levels. Inhibitory action on caspase-3 activity
      was not reversed by a selective antagonist of GHSR-1a. In conclusion, results of
      the present data clearly showed: (1) the presence of GHSR-1a in prepubertal pig
      ovary and found no influence of GH on GHSR-1a protein levels and mRNA expression,
      and (2) ghrelin effect on estradiol secretion, aromatase activity and cell
      proliferation dependent of its binding to GHSR-1a, while the effect on cellular
      apoptosis was independent of its binding to GHSR-1a.

PMID- 18809348
TI  - Insulin-like growth factor-I reduces stress-induced gastric mucosal injury by
      inhibiting neutrophil activation in mice.
AB  - OBJECTIVE: We previously reported that activated neutrophils are critically
      involved in the development of stress-induced gastric mucosal injury in mice.
      Caspase activation plays an important role in the pathogenesis of tissue injury
      by activating neutrophils through an increase in the expression of endothelial
      monocyte-activating polypeptide-II (EMAP-II), a chemoattractant for neutrophils.
      Since insulin-like growth factor-I (IGF-I) inhibits caspase activation, it is
      possible that IGF-I reduces gastric mucosal injury by inhibiting neutrophil
      activation. In the present study, we examined this possibility in mice subjected
      to water-immersion restraint stress (WIR). DESIGN: Mice were intraperitoneally
      administered with IGF-I or vehicle before being subjected to WIR. Gastric mucosal
      injury, gastric myeloperoxidase (MPO) activity, the immunofluorescence intensity
      of MPO, caspase-3 activity, number of apoptotic cells, EMAP-II expression and
      activation of Akt and glycogen synthase kinase-3beta (GSK-3beta) in gastric
      mucosa were determined in mice subjected to WIR. Neutropenia was induced by
      administration of methotrexate (MTX). RESULTS: Administration of IGF-I at dosages
      higher than 200 microg/kg significantly reduced gastric mucosal injury and
      inhibited increases in gastric MPO activities after 8h of WIR. Administration of
      MTX also reduced the gastric mucosal injury as well as inhibiting increases in
      both gastric mucosal MPO activities and circulating neutrophil number. IGF-I (500
      microg/kg) inhibited the increases in both gastric MPO activity and the
      immunofluorescence intensity of MPO observed in the gastric mucosa, but had no
      effect on the increase in circulating neutrophil number after 8h of WIR. It also
      markedly blunted WIR-induced increases in caspase-3 activities and the number of
      apoptotic cells in the gastric mucosa after 8h of WIR. Gastric expression of EMAP
      II was markedly increased at 8h after starting WIR and this increase was
      inhibited by IGF-I administration. Administration of IGF-I enhanced WIR-induced
      phosphorylation of Akt and GSK-3beta in the gastric mucosa. CONCLUSION: These
      observations indicate that IGF-I reduces stress-induced gastric mucosal injury by
      inhibiting gastric accumulation of neutrophils through inhibition of caspase-3
      mediated EMAP-II activation. Furthermore, IGF-I might inhibit caspase-3
      activation through Akt/GSK-3beta signaling.

PMID- 18809349
TI  - [Trapezio second metacarpal joint: anatomical study and clinical matters].
AB  - INTRODUCTION: An unusual dislocation of the column of the thumb associated with a
      fracture of the base of the second metacarpal inspired an anatomical study of the
      trapeziosecond metacarpal joint. MATERIALS AND METHODS: Forty-five dissections of
      the palmar aspect of trapeziometacarpal joint aimed at focusing on palmar
      ligaments and tendons reinforcing the joints. RESULTS: Trapeziosecond metacarpal
      joint is a constant little diarthrosis reinforced by a palmar ligament stressed
      between the crest of the trapezium and the base of the second metacarpal. The
      tendon of flexor radialis carpi muscle is an active link due to strong vinculae
      to trapezium bone and distal attachment to the bases of both second and third
      metacarpals. CONCLUSION: The connections between the trapezium and the base of
      the second metacarpal bone play a role in the treatment of thumb instability and
      their mechanical importance is illustrated in our original clinical observation.

PMID- 18809350
TI  - [Giant cystic widening of Virchow-Robin spaces, case report].
AB  - INTRODUCTION: Virchow-Robin spaces are very well-known anatomical and
      radiological entities. However, the observation of giant cystic widening of
      Virchow-Robin spaces is anecdotic. We report herein the case of a patient
      presenting with giant cystic widening of Virchow-Robin spaces located in both
      cerebral hemispheres. OBSERVATION: A 26-year-old female presented with numbness
      of left arm and then, of both arms. CT scan showed many hypodensities located in
      the two hemispheres. Neurologic examination was normal. MR imaging allowed the
      diagnosis of giant cystic widening Virchow-Robin spaces in T2, T2*, T1 gadolinium
      and Flair weighted images. Neuropsychological investigations were normal.
      CONCLUSION: Giant cystic widening of Virchow-Robin spaces are extremely rare
      entities. MR imaging helps the diagnosis. Only extreme dilatation of Virchow
      Robin perivascular spaces close to ventricular system must be watched and treated
      in case of an obstructive hydrocephalus risk. When located in cerebral
      hemispheres, these dilatations are mostly asymptomatic and must not be confused
      with a cystic tumoral disease.

PMID- 18809351
TI  - A reliable confirmation of the chemical structure of synthetic oligonucleotides:
      detection of active protons in DNA oligomers by low-temperature FT infrared
      spectroscopy.
AB  - Cooling the samples allowed us to characterize solid oligonucleotides such as
      dimers, trimers and pentamers of cytidine, for the first time, in the IR range of
      the out-of-plane bending molecular modes (1000-400 cm(-1)) at 20K. Especially
      interesting are the narrow IR bands of the out-of-plane bending nu(4) NH(2)
      proton mode, which are apparently invisible at room temperature. This
      unequivocally defined and well-resolved NH(2) bending band should provide
      important information on the exact chemical form and hydrogen bonding
      interactions of cytidine amine groups. As such, this unique IR spectroscopy is
      suggested as a practical analytical tool to validate and characterize synthetic
      DNA bases and oligonucleotides. Using an approach of this type it was found that
      desalted oligonucleotide samples of the same nominal composition, but which had
      been produced by three different manufacturers, differ significantly in their IR
      spectra. These data suggest that the presumably identical oligonucleotides are in
      fact different, at least with respect to the content and nature of their NH
      protons.

PMID- 18809352
TI  - Pulmonary telemedicine--a model to access the subspecialist services in
      underserved rural areas.
AB  - BACKGROUND: To describe the use of videoconference telemedicine for providing
      outpatient pulmonary consultation to a remote, underserved clinic site. METHODS:
      Analysis of data from the Milwaukee Veteran Affairs Medical Center (VAMC)
      pulmonary telemedicine clinic. Pulmonary physicians at the Milwaukee VAMC provide
      outpatient consultations with the use of videoconference technology to patients
      located at the Iron Mountain VAMC in Iron Mountain, MI (346 km or 215 miles from
      Milwaukee). Data on demographics, referral patterns, access to care, consultation
      process, and outcomes are presented. RESULTS: A total of 314 patients (684
      visits) received telemedicine consultations between January 1, 1998 and December
      31, 2004. Common reasons for referral were abnormal radiology (38%), chronic
      obstructive pulmonary disease (COPD) (26%), and dyspnea (13%). Physical exam was
      performed by the telemedicine registered nurse or respiratory therapists in 90%
      of visits. Common diagnoses were COPD (29%), benign pulmonary nodule (11%),
      bronchial asthma (6%), and lung cancer (6%). Telemedicine consultation resulted
      in a change in management for 41% of patients. Only 8% of patients required an in
      person clinic visit at Milwaukee VAMC following a telemedicine visit.
      Telemedicine saved patients 473,340 km or 294,120 miles of travel over the study
      period. CONCLUSIONS: The provision of subspecialty services using telemedicine to
      a remote underserved rural population provides improved patient access to
      subspecialty care. Physicians are able to rely on medical history and radiology
      to manage patients across a broad spectrum of complex pulmonary conditions with
      the assistance of a non-physician health care provider at the remote site.

PMID- 18809353
TI  - Large motor units are selectively affected following a stroke.
AB  - OBJECTIVE: Previous studies have revealed a loss of functioning motor units in
      stroke patients. However, it remained unclear whether the motor units are
      affected randomly or in some specific pattern. We assessed whether there is a
      selective loss of the large (high recruitment threshold) or the small (low
      recruitment threshold) motor units following a stroke. METHODS: Forty-five stroke
      patients and 40 healthy controls participated in the study. Macro-EMG was
      recorded from the abductor digiti minimi muscle at two levels of force output
      (low and high). The median macro motor unit potential (macro-MUP) amplitude on
      the paretic side was compared with those on the unaffected side and in the
      controls. RESULTS: In the control group and on the unaffected side, the macro
      MUPs were significantly larger at the high force output than at the low one.
      However, on the paretic side the macro-MUPs at the high force output had the same
      amplitude as those recorded at the low force output. These changes correlated
      with the severity of the paresis. CONCLUSIONS: Following a stroke, there is a
      selective functional loss of the large, high-threshold motor units. These changes
      are related to the severity of the symptoms. SIGNIFICANCE: Our findings furnish
      further insight into the pathophysiology of the motor deficit following a stroke.

PMID- 18809354
TI  - Studying adaptive motor control of the cerebellum by the precision grip paradigm.

PMID- 18809355
TI  - Stimulus-induced bilateral central periodic discharges, cortical myoclonus and
      arousal responses in mild reversible coma.
AB  - OBJECTIVE: To study the association between stimulus-induced periodic
      epileptiform discharges (PEDs), arousal EEG responses and limb jerking in a
      comatose patient with reversible viral encephalitis. METHODS: We recorded video
      EEG in Intensive Care Unit (ICU) for strictly clinical purposes. Back averaging
      was performed off-line using Neuroscan 4.3. RESULTS: We recorded spontaneous and
      stimulus-induced bilateral central PEDs (bi-central PEDs) that were followed by
      phasic vertex potentials, customarily considered as EEG arousal responses. Bi
      central PEDs were associated with myoclonus when provoked by strong and
      protracted stimuli, but remained subclinical when elicited by auditory or mild
      tactile stimuli. Spontaneous and stimulus-induced bi-central PEDs disappeared
      after full neurological recovery. CONCLUSION: These findings link stimulus
      induced PEDs to epileptic cortical myoclonus, and further suggest that in certain
      comatose patients they may represent reflex epileptic activity, even when
      clinically silent. The term "reflex seizures of the critically ill" may be
      appropriate in such patients. Our findings may also provide a model of the
      reciprocal relationship between arousals and epileptiform activity. SIGNIFICANCE:
      Consideration of the possibility that stimulus-induced PEDs are reflexive
      epileptic phenomena in some comatose ICU patients may rationalise further their
      acute management, including antiepileptic treatment.

PMID- 18809356
TI  - An evidence-based review of the literature on the consequences of conservative
      versus aggressive discectomy for the treatment of primary disc herniation with
      radiculopathy.
AB  - BACKGROUND CONTEXT: It remains unknown whether aggressive disc removal with
      curettage versus conservative removal of a disc fragment with little disc
      invasion provides a better outcome for the treatment of lumbar disc herniation
      with radiculopathy. PURPOSE: Determine the level of evidence within the clinical
      literature that supports the performance of a conservative versus aggressive
      technique for discectomy. STUDY DESIGN/SETTING: Systematic evidence-based review
      of clinical literature. PATIENT SAMPLE: Patients with primary lumbar disc
      herniation with radiculopathy. OUTCOME MEASURES: Operative time, return to work
      status, recurrent disc herniation, self-reported, and functional measures
      assessed less than 2 years (short term) and greater than 2 years (long term)
      after surgery. METHODS: Systematic Medline search was performed to identify all
      published studies relating to outcome after aggressive or conservative
      discectomy. Levels of evidence (I-V) were assessed for each study and grades of
      recommendation were generated (Good, Fair, Poor, Insufficient evidence) based on
      the NASS Clinical Guidelines' Levels of Evidence and Grades of Recommendation.
      RESULTS: There is fair evidence that conservative discectomy will result in
      shorter operative times and a quicker return to work despite similar lengths of
      hospital stay, similar pain levels at discharge, similar 6-month functional
      status, and a similar 2-year incidence of persistent/recurrent back and leg pain.
      There is poor quality evidence that conservative discectomy will result in a
      lower incidence of recurrent back pain beyond 2 years postoperatively. There is
      fair quality evidence that conservative discectomy will result in a higher
      incidence of recurrent disc herniation. CONCLUSIONS: There are no Level I studies
      to support conservative versus aggressive discectomy for the treatment of primary
      disc herniation. However, systematic review of the literature suggests that
      conservative discectomy may result in shorter operative time, quicker return to
      work, and a decreased incidence of long-term recurrent low back pain but with an
      increased incidence of recurrent disc herniation. Prospective randomized trails
      are needed to firmly assess this possible benefit.

PMID- 18809357
TI  - Relationship between the length of time off work preoperatively and clinical
      outcome at 24-month follow-up in patients undergoing total disc replacement or
      fusion.
AB  - BACKGROUND CONTEXT: A recent study involving interbody fusion patients found that
      preoperative work status was significantly related to clinical outcome. In
      another study comparing the best and worst outcomes of total disc replacement,
      among a battery of variables analyzed, the only one that differentiated the best
      and worst outcome groups was the length of time off work before total disc
      replacement. PURPOSE: The purpose of this study was to determine if there was a
      relationship between the length of time off work and treatment outcome at 24
      month follow-up. If such a relationship existed, a secondary study objective
      would be to determine if a duration of work could be identified beyond which
      would be associated with compromised clinical outcome. STUDY DESIGN AND SETTING:
      Data were collected prospectively from randomized clinical trials comparing total
      disc replacement with lumbar fusion conducted at a single site. PATIENT SAMPLE: A
      database of 232 patients enrolled in one of two Food and Drug Administration
      regulated trials comparing total disc replacement with fusion for the treatment
      of symptomatic disc degeneration was the basis of the study group. Only patients
      who had reached 24-month follow-up were included. The 28 patients who were not
      employed by choice preoperatively were not included in the analysis. OUTCOME
      MEASURES: Primary outcome measures used were visual analog scales (VAS) assessing
      pain and Oswestry disability index. METHODS: The length of time off work before
      surgery was recorded in weeks. The mean percentage improvement between
      preoperative and 24-month follow-up scores were analyzed. RESULTS: There was a
      significant relationship between duration off work preoperatively and clinical
      outcome (p<.05). The length of time off work preoperatively was more strongly
      related to outcome than was surgery type, insurance type, job demand, or
      preoperative VAS and Oswestry scores. Further analysis of the data identified a
      window of approximately 0 to 13 weeks off work preoperatively that was related to
      significantly greater improvements on visual analog scales (VAS) and Oswestry
      scores after surgery compared with patients who were off work for more than 13
      weeks preoperatively. Although the subgroup off work for more than 13 weeks
      improved significantly from their preoperative status, the improvement was not as
      great as in the subgroup off work for a shorter duration. CONCLUSIONS: The
      results of this study found that patients off work for a longer duration before
      surgery improved significantly postoperatively, but had less favorable clinical
      outcomes than patients off work for a lesser duration. This study suggests a
      window of approximately 13 weeks off work before surgery after which clinical
      improvement is reduced. Implications of this finding may be that once a patient
      becomes unable to work for an extended period, more rigorous psychological
      screening may be in order as well as perhaps engaging in more rigorous
      rehabilitation after surgery. Further investigation is needed to determine if the
      13 weeks identified in this study is applicable to other populations.

PMID- 18809358
TI  - Fluoroscopic percutaneous lumbar zygapophyseal joint cyst rupture: a clinical
      outcome study.
AB  - BACKGROUND CONTEXT: Lumbar zygapophyseal joint (Z-joint) synovial cysts can cause
      low back pain (LBP), spinal stenosis, and lower extremity radiculopathy. In the
      literature, there are several minimally invasive techniques described with mixed
      results. Typical recommended treatment is surgical resection of the cyst.
      Currently, there is little information available concerning the efficacy and
      outcome with treatment of Z-joint synovial cyst by percutaneous, fluoroscopic,
      contrast-enhanced distention, and rupture. PURPOSE: To evaluate the therapeutic
      value and safety of Z-joint cyst rupture in symptomatic patients. STUDY
      DESIGN/SETTING: Retrospective cohort study in an academic outpatient physiatric
      spine practice. PATIENT SAMPLE: Thirty-two patients with moderate-to-severe LBP
      and leg pain (18 women and 14 men with an age range of 46-86 y; mean age, 66 y)
      with an average preprocedure symptom duration of 5 months. The patient's clinical
      symptoms correlated with magnetic resonance imaging studies documenting the
      presence of a synovial cyst at the corresponding level and side of symptoms.
      Patients had at least 6 months follow-up (range, 6-24). OUTCOME MEASURES:
      Numerical Pain Rating Scale, Roland-Morris Disability Questionnaire, North
      American Spine Society four-point patient satisfaction survey, recurrence of
      synovial cyst requiring repeat rupture, and need for surgical intervention.
      METHODS: Patients with symptomatic lumbar Z-joint synovial cyst were identified
      and their charts were reviewed. Patients included in the study either had
      symptomatic lumbar LBP or LBP with associated lower extremity radiculopathy. All
      patients in the study had magnetic resonance imaging's documenting Z-joint
      synovial cyst that corresponded with the patients' clinical symptoms. All
      patients received fluoroscopically guided, contrast-enhanced, percutaneous facet
      cyst distention and rupture followed by an intra-articular facet joint injection
      of 1 cc kenalog and 1 cc of 1% lidocaine. Seventeen of the patients also received
      a transforaminal epidural steroid injection just before facet cyst rupture.
      Telephone follow-up was conducted on all patients. RESULTS: Excellent long-term
      (average follow-up 1 y; range, 6-24 mo) pain relief was achieved in 23 (72%) of
      32 patients undergoing facet cyst rupture. Twelve patients (37.5%) had synovial
      cyst recurrence and 11 chose to undergo repeat rupture, which resulted in 5
      patients (45%) obtaining complete relief of symptoms and 6 patients (55%)
      requiring surgical intervention for cyst removal. Fisher exact test demonstrated
      that all patients who did not have a cyst recurrence were a success and obtained
      complete relief of symptoms (p<.0002). Patients who underwent a repeat rupture
      had a 50% chance of a successful outcome. There was no statistical significance
      between a successful outcome and level of facet cyst rupture, the presence of
      spondylolisthesis, sex, age, or having a transforaminal epidural steroid
      injection at the time of the procedure. Wilcoxon signed-rank test demonstrated
      that the difference in Numerical Pain Rating Scale and Roland-Morris Disability
      Questionnaire scores before and after the procedure was statistically significant
      (p<.0001). No complications were reported. CONCLUSIONS: Fluoroscopic percutaneous
      Z-joint cyst rupture appears to be a safe and effective minimally invasive
      treatment option. This procedure should be considered before surgical
      intervention.

PMID- 18809359
TI  - Someone needs to claim it!

PMID- 18809360
TI  - X-Stop: foot drop.
AB  - BACKGROUND CONTEXT: The X-Stop (Kyphon, Sunnyvale, CA), a device implanted
      between adjacent lumbar spinous processes at one or two levels particularly in
      the geriatric population, theoretically decompresses the spinal canal by
      reversing the lordosis. PURPOSE: The X-Stop relieves the symptoms of lumbar
      stenosis. STUDY DESIGN/SETTING: A case report from the United States. PATIENT
      SAMPLE: A case report focusing on how X-Stop placement resulted in a bilateral
      foot drop in an 84-year-old patient, which was relieved 9 months later with
      laminectomy. OUTCOME MEASURES: The patient's outcome was based on the
      neurological examination. METHODS: An 84-year-old male with lumbar neurogenic
      claudication/radiculopathy, exhibited magnetic resonance (MR)-documented L4-L5
      lumbar stenosis and Grade I degenerative spondylolisthesis. At an outside
      institution, an L4-L5 X-Stop was placed; he immediately developed a bilateral
      foot drop. Three months later, the X-Stop extruded, and was removed; his foot
      drop remained unchanged. Nine months after the original surgery, based on new
      MR/computed tomography (CT) documented severe (L2-L3, L4-L5), moderate (L1-L2, L3
      L4, L5-S1) stenosis, and the L4-L5 Grade I degenerative spondylolisthesis, the
      second surgeon performed an L1-S1 laminectomy with L4-L5 noninstrumented fusion.
      RESULTS: Postoperatively, the patient's bilateral foot drop largely resolved.
      CONCLUSIONS: Placing the X-Stop device at severely stenotic levels, particularly
      when accompanied by degenerative spondylolisthesis, may contribute to significant
      postoperative neurological sequelae in geriatric patients. For those with limited
      comorbidities, operative decompression may prove the safer alternative.

PMID- 18809361
TI  - Pressor responses to nasal stimulation are unaltered after disrupting the CPA.
AB  - Stimulation of either the caudal pressor area (CPA) in the most caudal
      ventrolateral medulla with glutamate, or the nasal mucosa with ammonia vapors,
      induces an increase in mean arterial blood pressure (MABP). In the present study,
      we determined if neurons in the CPA serve as a relay for the increase in MABP
      seen after nasal stimulation. Ammonia vapors stimulated the nasal mucosa of rats
      anesthetized with either urethane alone or ketamine/xylazine and urethane to
      induce an increase in MABP, a bradycardia, and an apnea. Bilateral injections (50
      nl) of glycine (1 M) or muscimol (2 mM) were placed in the CPA and the nasal
      mucosa again stimulated. The increases in MABP, the bradycardia and the duration
      of apnea to nasal stimulation were unchanged after either injection. However,
      resting MABP and HR were decreased significantly after glycine injections and
      resting MABP and resting respiratory rate were decreased after muscimol
      injections. The increase in MABP seen with nasal stimulation also did not change
      after multiple bilateral injections (3x40 nl) of ibotenate (5 microg/microl) in
      the CPA, but the bradycardia was eliminated and the duration of apnea was
      significantly shorter. These results suggest that the increase in MABP induced by
      nasal stimulation is via routes that do not include neurons in the CPA.

PMID- 18809362
TI  - Socioeconomic status and physical stature in 19th-century Bavaria.
AB  - We present analyses of 19th-century Bavarian conscript records, which cover the
      whole male population at age 21 and which are unusually rich in content. They
      include not only occupations of the conscripts, but that of the parents alike,
      and also the wealth of the conscripts, other family characteristics and their
      diseases at the time of the conscription. This enables us to investigate the
      relationship between the conscripts' and the parents' socioeconomic status as
      well as their effects on the height of the conscripts. Overall, the conscripts'
      occupations match that of their parents rather well, and deviations can mainly be
      attributed to their young age. However, we also find significant height
      differences between the occupational groups of the conscripts even after
      controlling for the parents' occupations. This could be caused by a reverse
      effect of height on occupational advancements, but as conscripts doing manual
      work are generally shorter than those with non-manual occupations irrespective of
      their rank, we assume that the working conditions of the adolescents and young
      men actually influenced their growth.

PMID- 18809363
TI  - A new approach to graft bioactive polymer on titanium implants: Improvement of MG
      63 cell differentiation onto this coating.
AB  - Integration of titanium implants into bone is only passive and the resulting
      fixation is mainly mechanical in nature, with anchorage failure. Our objective,
      to increase the biointegration of the implant and the bone tissue, could be
      obtained by grafting a bioactive ionic polymer to the surface of the titanium by
      a covalent bond. In this paper, we report the grafting of an ionic polymer model
      poly(sodium styrene sulfonate) (polyNaSS), in a two-step reaction procedure.
      Treatment of the titanium surface by a mixture of sulfuric acid and hydrogen
      peroxide allows the formation of titanium hydroxide and titanium peroxide. In the
      second reaction step, heating of a metal implant, placed in a concentrated
      solution of sodium styrene sulfonate monomer (NaSS), induces the decomposition of
      titanium peroxides with the formation of radicals capable of initiating the
      polymerization of NaSS. Various parameters, such as temperature of polymerization
      and time of polymerization, were studied in order to optimize the yield of
      polyNaSS grafting. Colorimetry, Fourier-transformed infrared spectra recorded in
      an attenuated total reflection, X-ray photoelectron spectroscopy 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 samples compared to
      unmodified surfaces.

PMID- 18809364
TI  - Morphological and functional studies of rat hepatocytes on a hydrophobic or
      hydrophilic polydimethylsiloxane surface.
AB  - This study describes the morphological and functional behavior of rat hepatocytes
      on a polydimethylsiloxane (PDMS)-coated surface. Hepatocytes were cultured on
      hydrophobic or hydrophilic PDMS-coated surfaces in serum-free and serum
      containing media. In the serum-free medium, almost all hepatocytes adhered onto
      the surface irrespective of the wettability, with a cell adhesion ratio of >90%
      at 24h. In the serum-containing medium, although they strongly adhered onto the
      hydrophilic surface (cell adhesion ratio >85%), the ratio on the hydrophobic
      surface was <15%. Furthermore, hepatocytes in the serum-free medium gradually
      formed spheroids irrespective of the surface characteristics; however, on the
      hydrophilic surface in the serum-containing medium, they maintained a monolayer
      configuration for up to 10 days, and their numbers gradually decreased over time.
      Expression levels of the functional activities (albumin secretion and ammonia
      removal) and the cell-cell adhesion molecules (cadherin and connexin-32) were
      higher in the hepatocytes that formed spheroids compared to those which assumed a
      monolayer configuration, and these levels were maintained for at least 10 days.
      These results suggest that the wettability of PDMS and the composition of the
      culture medium together control the cell adhesion, morphology and expression of
      functional genes in hepatocytes.

PMID- 18809365
TI  - The routine sampling of internal mammary nodes as part of breast reconstruction.

PMID- 18809366
TI  - Nipple reconstruction using a modified arrow flap technique.

PMID- 18809367
TI  - [Atherosclerotic renal artery disease diagnosis update].
AB  - Atherosclerotic renal artery disease represents a cause of which little is known
      but not a cause to be neglected for hypertension and renal insufficiency. Even
      though its occurrence remains badly defined, atherosclerotic renal artery disease
      is constantly on the rise due to the aging population, the never prevailing
      hypertension and diabetes mellitus. This review aims to give a clinical profile
      of patients presenting with atherosclerotic renal artery disease and to discuss,
      in the light of study results, which diagnostic evaluation should be used
      considering the sequence and the benefit and risk of each in order to initiate a
      personalized treatment. Patients affected by atherosclerotic renal artery disease
      are likely to have more complications and more extensive target-organ damage than
      patients without renal artery stenosis. The evolution of the atherosclerotic
      renal artery disease is in general slow and progressive. Nevertheless, certain
      clinical cases manifest themselves with the onset of acute renal failure bought
      upon by the administration of blockers of the rennin-angiotensin-aldosterone
      system, or by some other causes responsible for a sudden drop in renal plasma
      flow (e.g., thrombosis of the renal artery). The relationship between
      atherosclerotic renal artery disease and atherosclerosis is complex, and
      mediators implicated in the pathophysiology of renovascular disease may also
      contribute to the progression of cardiovascular damage. An early assumption of
      the atherosclerotic renal artery stenosis is warranted to determine the adapted
      treatment (i.e., medical treatment, revascularisation...) just as the assumption
      and the correction of the more general cardiovascular risk factors.

PMID- 18809368
TI  - [The nutcracker syndrome].
AB  - The nutcracker syndrome refers to compression of the left renal vein between the
      aorta and the superior mesenteric artery. After a review of the literature, the
      authors emphasize the uncommon incidence of this pathology, and the interest of
      imaging in the survey of this affection.

PMID- 18809369
TI  - [Postinfectious acute glomerulonephritis].
AB  - Postinfectious acute glomerulonephritis mostly happens in children aged two to 10
      years old. Typically, it follows group A beta-hemolytic streptococcus skin or
      upper respiratory tract infection. There is a latent period of one to three weeks
      before nephritic syndrome appears. Microscopic or macroscopic hematuria is always
      present. Proteinuria and decreased glomerular filtration rate are usually mild.
      By contrast, salt and water retention can be severe and complicated with
      hypertension, congestive heart failure or pulmonary edema. Fluid overload must be
      urgently treated by loop diuretics or renal replacement therapy in the most
      severe cases.

PMID- 18809370
TI  - [How to optimize the concept of the variability of haemoglobin in dialysis
      patients].

PMID- 18809371
TI  - Role of the calpain-calpastatin system in the density-dependent growth arrest.
AB  - In dividing cells calpastatin diffuses from aggregates into cytosol, indicating
      the requirement for a tight regulation of calpain. Accordingly, the involvement
      of the calpain-calpastatin system in cell proliferation and in the density
      dependent growth arrest was studied in JA3 cells stably transfected with a
      calpastatin form permanently localized in cytosol. In calpastatin overexpressing
      cells, cell cycle rate is 50% reduced, and cells enter the ungrowing, still fully
      reversible, stage at a 3-fold higher cell density. Furthermore, in cell density
      growth arrest phase, down regulation of alpha- and theta-PKC isoforms, as well as
      FAK and talin occurs. In calpastatin overexpressing cells, degradation of these
      calpain substrate proteins is prevented and delayed. Thus, calpain activity plays
      a crucial role in inducing the cell entry into a functional quiescent phase.

PMID- 18809372
TI  - Biotin protein ligase from Candida albicans: expression, purification and
      development of a novel assay.
AB  - Biotin protein ligase (BPL) is an essential enzyme responsible for the activation
      of biotin-dependent enzymes through the covalent attachment of biotin. In yeast,
      disruption of BPL affects important metabolic pathways such as fatty acid
      biosynthesis and gluconeogenesis. This makes BPL an attractive drug target for
      new antifungal agents. Here we report the cloning, recombinant expression and
      purification of BPL from the fungal pathogen Candida albicans. The biotin domains
      of acetyl CoA carboxylase and pyruvate carboxylase were also cloned and
      characterised as substrates for BPL. A novel assay was established thereby
      allowing examination of the enzyme's properties. These findings will facilitate
      future structural studies as well as screening efforts to identify potential
      inhibitors.

PMID- 18809373
TI  - The negatively charged amino acids in the lumenal loop influence the pigment
      binding and conformation of the major light-harvesting chlorophyll a/b complex of
      photosystem II.
AB  - The major chlorophyll (Chl) a/b complexes of photosystem II (LHCIIb), in addition
      to their primary light-harvesting function, play key roles in the organization of
      the granal ultrastructure of the thylakoid membranes and in various regulatory
      processes. These functions depend on the structural stability and flexibility of
      the complexes. The lumenal side of LHCIIb is exposed to broadly variable pH
      environments, due to the build-up and decay of the pH gradient during
      photosynthesis. Therefore, the negatively charged amino acids in the lumenal loop
      might be of paramount importance for adjusting the structure and functions of
      LHCIIb. In order to clarify the structural roles of these residues, we
      investigated the pigment stoichiometries, absorption, linear and circular
      dichroism spectra of the reconstituted LHCIIb complexes, in which the negatively
      charged amino acids in the lumenal loop were exchanged to neutral ones (E94G,
      E107V and D111V). The mutations influenced the pigment binding and the molecular
      architecture of the complexes. Exchanging E94 to G destabilized the 3(10) helix
      in the lumenal loop structure and led to an acquired pH sensitivity of the LHCIIb
      structure. We conclude that these amino acids are important not only for pigment
      binding in the complexes, but also in stabilizing the conformation of LHCIIb at
      different pHs.

PMID- 18809374
TI  - The antimicrobial peptide gramicidin S permeabilizes phospholipid bilayer
      membranes without forming discrete ion channels.
AB  - We examined the permeabilization of lipid bilayers by the beta-sheet, cyclic
      antimicrobial decapeptide gramicidin S (GS) in phospholipid bilayers formed
      either by mixtures of zwitterionic diphytanoylphosphatidylcholine and anionic
      diphytanoylphosphatidylglycerol or by single zwitterionic unsaturated
      phosphatidylcholines having various hydrocarbon chain lengths, with and without
      cholesterol. In the zwitterionic bilayers formed by the phosphatidylcholines,
      without or with cholesterol, the peptide concentrations and membrane potentials
      required to initiate membrane permeabilization vary little as function of bilayer
      thickness and cholesterol content. In all the systems tested, the GS-induced
      transient ion conductance events exhibit a broad range of conductances, which are
      little affected by the bilayer composition or thickness. In the zwitterionic
      phosphatidylcholine bilayers, the effect of GS does not depend on the polarity of
      the transmembrane potential; however, in bilayers formed from mixtures of
      phosphatidylcholines and anionic phospholipids, the polarity of the transmembrane
      potential becomes important, with the GS-induced conductance events being much
      more frequent when the GS-containing solution is positive relative to the GS-free
      solution. Overall, these results suggest that GS does not form discrete, well
      defined, channel-like structures in phospholipid bilayers, but rather induces a
      wide variety of transient, differently sized defects which serve to compromise
      the bilayer barrier properties for small electrolytes.

PMID- 18809375
TI  - Interactions of ciprofloxacin with DPPC and DPPG: fluorescence anisotropy, ATR
      FTIR and 31P NMR spectroscopies and conformational analysis.
AB  - The interactions between a drug and lipids may be critical for the
      pharmacological activity. We previously showed that the ability of a
      fluoroquinolone antibiotic, ciprofloxacin, to induce disorder and modify the
      orientation of the acyl chains is related to its propensity to be expelled from a
      monolayer upon compression [1]. Here, we compared the binding of ciprofloxacin on
      DPPC and DPPG liposomes (or mixtures of phospholipids [DOPC:DPPC], and
      [DOPC:DPPG]) using quasi-elastic light scattering and steady-state fluorescence
      anisotropy. We also investigated ciprofloxacin effects on the transition
      temperature (T(m)) of lipids and on the mobility of phosphate head groups using
      Attenuated Total Reflection Fourier Transform Infrared-Red Spectroscopy (ATR
      FTIR) and (31)P Nuclear Magnetic Resonance (NMR) respectively. In the presence of
      ciprofloxacin we observed a dose-dependent increase of the size of the DPPG
      liposomes whereas no effect was evidenced for DPPC liposomes. The binding
      constants K(app) were in the order of 10(5) M(-1) and the affinity appeared
      dependent on the negative charge of liposomes: DPPG>DOPC:DPPG (1:1;
      M:M)>DPPC>DOPC:DPPC (1:1; M:M). As compared to the control samples, the chemical
      shift anisotropy (Deltasigma) values determined by (31)P NMR showed an increase
      of 5 and 9 ppm for DPPC:CIP (1:1; M:M) and DPPG:CIP (1:1; M:M) respectively. ATR
      FTIR experiments showed that ciprofloxacin had no effect on the T(m) of DPPC but
      increased the order of the acyl chains both below and above this temperature. In
      contrast, with DPPG, ciprofloxacin induced a marked broadening effect on the
      transition with a decrease of the acyl chain order below its T(m) and an increase
      above this temperature. Altogether with the results from the conformational
      analysis, these data demonstrated that the interactions of ciprofloxacin with
      lipids depend markedly on the nature of their phosphate head groups and that
      ciprofloxacin interacts preferentially with anionic lipid compounds, like
      phosphatidylglycerol, present at a high content in these membranes.

PMID- 18809376
TI  - A new approach for selective rat endolymphatic sac epithelium collection to
      obtain pure specific RNA.
AB  - The endolymphatic sac (ES) is an organ that is located in the temporal bone. Its
      anatomical location makes ES tissue collection without any contamination very
      difficult, and sometimes accurate molecular analyses of the ES are prevented due
      to this matter. In the present study, a new selective ES epithelial tissue
      collection method was attempted using laser capture microdissection to obtain
      pure ES RNA without any contamination. The validity of this method was
      demonstrated by RT-PCR with three specific primer pairs against osteocalcin,
      calponin H1, and NKCC2, which are specific proteins in bone, smooth muscle, and
      kidney/ES cells, respectively. From the RT-PCR results, the high specificity and
      sufficient sensitivity of the new method was indicated. It is considered that the
      new method is optimal for ES collection without contamination and it will be able
      to contribute to future analyses of the ES.

PMID- 18809377
TI  - Attenuated BDNF-induced upregulation of GABAergic markers in neurons lacking
      Xbp1.
AB  - XBP1 is a transcription factor induced by unconventional splicing associated with
      endoplasmic reticulum stress and plays a role in development. Brain-derived
      neurotrophic factor (BDNF) causes splicing of Xbp1 mRNA in neurites, and Xbp1 is
      required for BDNF-induced neurite extension and branching. To search for the
      molecular mechanisms of how Xbp1 plays a role in neural development,
      comprehensive gene expression analysis was performed in primary telencephalic
      neurons obtained from Xbp1 knockout mice at embryonic day 12.5. By searching for
      the genes induced by BDNF in wild type neurons but not in Xbp1 knockout mice, we
      found that upregulation of three GABAergic markers, somatostatin (Sst),
      neuropeptide Y (Npy), and calbindin (Calb1), were compromised in Xbp1 knockout
      neurons. Attenuated upregulation of Npy and Calb1 in Xbp1 knockout neurons was
      confirmed by quantitative RT-PCR. This finding may be relevant to impaired BDNF
      induced neurite extension in Xbp1 knockout neurons.

PMID- 18809378
TI  - Rad9 is upregulated and plays protective roles in an acute lung injury model.
AB  - The Rad9-Hus1-Rad1 protein complex is believed to respond to DNA damage and play
      important roles in the cell cycle. We studied the role of Rad9 protein in
      alveolar epithelial cells in the pathogenesis of acute lung injury. In a mouse
      model of lung injury induced by bleomycin or lipopolysaccharide, Rad9 expression
      is increased in type II alveolar epithelial cells from the early stage of lung
      injury. A549 cells and mouse primary alveolar epithelial cells also upregulated
      Rad9 expression after exposure to bleomycin. Gene silencing of Rad9 using siRNA
      decreased the G2/M arrest in A549 cells induced by bleomycin and also decreased
      the survival of A549 cells following exposure to bleomycin and hydrogen peroxide.
      In conclusion, Rad9 is a signal in the earlier stage of epithelial cell cycle
      regulation and plays protective roles in alveolar epithelial cells in the
      pathogenesis of acute lung injury.

PMID- 18809379
TI  - NS-398, a selective COX-2 inhibitor, inhibits proliferation of IL-1beta
      stimulated vascular smooth muscle cells by induction of HO-1.
AB  - We investigated whether NS-398, a selective inhibitor of COX-2, induces HO-1 in
      IL-1beta-stimulated vascular smooth muscle cells (VSMC). NS-398 reduced the
      production of PGE(2) without modulation of expression of COX-2 in IL-1beta
      stimulated VSMC. NS-398 increased HO-1 mRNA and protein in a dose-dependent
      manner, but inhibited proliferation of IL-1beta-stimulated VSMC. Furthermore,
      SnPPIX, a HO-1 inhibitor, reversed the effects of NS-398 on PGE(2) production,
      suggesting that COX-2 activity can be affected by HO-1. Hemin, a HO-1 inducer,
      also reduced the production of PGE(2) and proliferation of IL-1beta-stimulated
      VSMC. CORM-2, a CO-releasing molecule, but not bilirubin inhibited proliferation
      of IL-1beta-stimulated VSMC. NS-398 inhibited proliferation of IL-1beta
      stimulated VSMC in a HbO(2)-sensitive manner. In conclusion, NS-398 inhibits
      proliferation of IL-1beta-stimulated VSMC by HO-1-derived CO. Thus, NS-398 may
      facilitate the healing process of vessels in vascular inflammatory disorders such
      as atherosclerosis.

PMID- 18809380
TI  - Tissue transglutaminase-induced down-regulation of matrix metalloproteinase-9.
AB  - Tissue transglutaminase (TGase 2) has been reported to have multiple functions in
      addition to its function as a biological adhesive. To identify its roles, we
      investigated the effects of TGase 2 on gelatinase activity. The MMP-9 activity of
      certain cell lines was significantly inhibited with retinoic acid treatment, and
      this effect was reversed in the presence of a TGase 2 inhibitor. Furthermore,
      TGase 2 overexpression reduced the MMP-9 protein expression levels and inhibited
      its activity in both culture media and cell lysate. The decreased mRNA levels of
      MMP-9 and the results of a promoter assay revealed that TGase 2 may be involved
      in MMP-9 transcription. Further, data obtained in an immunoprecipitation assay
      and an electrophoretic mobility shift assay demonstrated that TGase 2 binds to c
      Jun and suppresses its binding activity toward AP-1. These results suggest that
      TGase 2 inhibits MMP-9 via downregulation of MMP-9 transcription activity by
      blocking the binding of the Jun-fos complex to an AP-1 site.

PMID- 18809381
TI  - Regulation of brain insulin mRNA by glucose and glucagon-like peptide 1.
AB  - Whether the brain synthesizes insulin is currently debated. Two clonal,
      immortalized mouse hypothalamic cell lines from e17, mHypoE-39 and mHypoE-46,
      express insulin 2 (Ins2), but not Ins1. We analyzed regions necessary for basal
      gene activity and found that the mouse Ins2 region -110/+183 bp stimulates
      promoter activity in hypothalamic neurons. The rat Ins2 showed moderate activity,
      whereas the human promoter construct is repressed below basal levels. In MIN6
      pancreatic beta-cells, all of the Ins1 and Ins2 promoter constructs display high
      levels of transcriptional activity. The cell lines also express components of
      glucose-sensing machinery and the endogenous glucagon-like peptide 1 receptor
      (Glp-1R). We observed that 16.7 mM glucose induces Ins2 mRNA, while forskolin and
      a Glp-1 agonist, exendin-4, induce a biphasic Ins2 mRNA response in mHypoE-39
      neurons. The insulin cis-regulatory regions differ between the pancreas and the
      hypothalamus, and glucose and Glp-1 regulate the expression of hypothalamic
      insulin.

PMID- 18809382
TI  - Cytoplasmic and serum galectin-3 in diagnosis of thyroid malignancies.
AB  - In order to address whether galectin-3 in the sera and fine needle aspirates
      serve as a diagnostic marker distinguishing between benign and malignant thyroid
      nodules, we developed an enzyme-linked immunosorbent assay. We quantified
      galectin-3 in fine needle aspirates from a series of 118 patients with thyroid
      nodules and serum galectin-3 from another series of 46 patients, which were
      compared with final histology after thyroidectomy. Relative galectin-3 value
      (ng/mg), defined as galectin-3 concentration (ng/ml) divided by total protein
      concentration (mg/ml) in fine needle aspirates, was significantly higher in
      papillary carcinoma than in the other thyroid entities. There was no significant
      difference in serum galectin-3 level among patients with thyroid nodules and
      healthy individuals. Accordingly, relative galectin-3 value allows a definitive
      diagnosis of papillary carcinoma independent of cellular morphology, whereas
      serum galectin-3 does not serve as a marker for papillary carcinoma.

PMID- 18809383
TI  - Crystal structure of the Bruton's tyrosine kinase PH domain with
      phosphatidylinositol.
AB  - Bruton's tyrosine kinase (Btk) of the Tec family possesses a Pleckstrin homology
      (PH) domain, which is responsible for plasma membrane targeting. In this study,
      the crystal structure of the Btk PH domain in complex with dibutylyl
      phosphatidylinositol-3,4,5-triphosphate was determined. The structure revealed
      that the Btk PH domain forms a homodimer and that each molecule binds
      phosphatidylinositol in the binding pocket. The side chain of Lys18 within a Btk
      specific insertion in the beta1-beta2 loop is able to form a hydrogen bond with
      the diacylglycerol moiety of phosphatidylinositol. The other Btk-specific
      insertion in the beta5-beta6 loop constitutes the dimerization interface. Thus,
      the modes of phosphatidylinositol recognition and Btk PH domain dimerization are
      distinct from those of other PH domains.

PMID- 18809384
TI  - Rapid identification of Plasmodium-carrying mosquitoes using loop-mediated
      isothermal amplification.
AB  - With an aim to develop a quick and simple method to survey pathogen-transmitting
      vectors, LAMP (loop-mediated isothermal amplification) was applied to the
      identification of Plasmodium-carrying mosquitoes, specifically a Plasmodium
      transmitting experimental model using rodent malaria parasite (Plasmodium
      berghei) and anopheline mosquitoes (Anopheles stephensi). The detection
      sensitivity limit of the LAMP reaction amplifying the SPECT2 gene was determined
      to be 1 x 10(2) purified Plasmodium parasites, estimated to be sufficient for
      reliable identification of infectious mosquitoes. The robustness of the LAMP
      reaction was revealed by its ability to detect both Plasmodium oocysts and
      sporozoites from an "all-in-one" template using whole mosquito bodies. Moreover,
      LAMP successfully identified an infectious mosquito carrying just a single oocyst
      in its midgut, a level that can be easily overlooked in conventional microscopic
      analysis. These observations suggest that LAMP is more reliable and useful for
      routine diagnosis of vector mosquitoes in regions where vector-borne diseases
      such as malaria are endemic.

PMID- 18809385
TI  - Up-regulated expression of microRNA-143 in association with obesity in adipose
      tissue of mice fed high-fat diet.
AB  - MicroRNAs (miRNAs) are short non-coding RNA that post-transcriptionally regulates
      gene expression. miR-143 has been proposed to play a role in the differentiation
      of adipocytes in culture. However, the mechanism regulating the expression of miR
      143 in adult adipose tissue during the development of obesity in vivo is unknown.
      Here in, we showed that the expression of miR-143 in the mesenteric fat was up
      regulated in mice fed a high-fat diet. Increased miR-143 expression was
      associated with an elevated body weight and mesenteric fat weight. Furthermore,
      miR-143 levels were closely correlated with expression levels of adipocyte
      differentiation markers such as PPARgamma and aP2 as well as plasma levels of
      leptin, one of the important adipocytokines involved in insulin resistance. These
      findings provide the first evidence for the up-regulated expression of miR-143 in
      the mesenteric fat of high-fat diet-induced obese mice, which might contribute to
      the regulated expression of adipocyte genes involved in the pathophysiology of
      obesity.

PMID- 18809386
TI  - Sp1-mediated transcription regulation of TAF-Ialpha gene encoding a histone
      chaperone.
AB  - TAF-I, one of histone chaperones, consists of two subtypes, TAF-Ialpha and TAF
      Ibeta. The histone chaperone activity of TAF-I is regulated by dimer patterns of
      these subtypes. TAF-Ibeta is expressed ubiquitously, while the expression level
      of TAF-Ialpha with less activity than TAF-Ibeta differs among cell types. It is,
      therefore, assumed that the expression level of TAF-Ialpha in a cell is important
      for the TAF-I activity level. Here, we found that TAF-Ialpha and TAF-Ibeta genes
      are under the control of distinct promoters. Reporter assays and gel shift assays
      demonstrated that Sp1 binds to three regions in the TAF-Ialpha promoter and two
      or all mutaions of the three Sp1 binding regions reduced the TAF-Ialpha promoter
      activity. ChIP assays demonstrated that Sp1 binds to the TAF-Ialpha promoter in
      vivo. Furthermore, the expression level of TAF-Ialpha mRNA was reduced by
      knockdown of Sp1 using siRNA method. These studies indicated that the TAF-Ialpha
      promoter is under the control of Sp1.

PMID- 18809387
TI  - Activated macrophages down-regulate podocyte nephrin and podocin expression via
      stress-activated protein kinases.
AB  - The development of proteinuria and glomerulosclerosis in kidney disease is
      associated with podocyte damage, including down-regulation of nephrin and
      podocin. Macrophages are known to induce renal injury, but the mechanisms
      involved are not fully understood. This study examined macrophage-mediated
      podocyte damage. Conditioned media (CM) from activated macrophages caused a 50
      60% reduction in nephrin and podocin mRNA and protein expression in cultured
      mouse podocytes and rat glomeruli. This was abolished by a neutralizing anti
      TNFalpha antibody. The addition of recombinant TNFalpha to podocytes or glomeruli
      caused a comparable reduction in podocyte nephrin and podocin expression to that
      of macrophage CM. Inhibition of c-Jun amino terminal kinase (JNK) or p38 kinase
      abolished the TNFalpha-induced reduction in nephrin and podocin expression. This
      study demonstrates that activated macrophages can induce podocyte injury via a
      TNFalpha-JNK/p38-dependent mechanism. This may explain, in part, the protective
      effects of JNK and p38 blockade in experimental kidney disease.

PMID- 18809388
TI  - The C. elegans mitochondrial K+(ATP) channel: a potential target for
      preconditioning.
AB  - Ischemic preconditioning (IPC) is an evolutionarily conserved endogenous
      mechanism whereby short periods of non-lethal exposure to hypoxia alleviate
      damage caused by subsequent ischemia reperfusion (IR). Pharmacologic targeting
      has suggested that the mitochondrial ATP-sensitive potassium channel (mK(ATP)) is
      central to IPC signaling, despite its lack of molecular identity. Here, we report
      that isolated Caenorhabditis elegans mitochondria have a K(ATP) channel with the
      same physiologic and pharmacologic characteristics as the vertebrate channel.
      Since C. elegans also exhibit IPC, our observations provide a framework to study
      the role of mK(ATP) in IR injury in a genetic model organism.

PMID- 18809389
TI  - Involvement of basic amino acid residues in transmembrane regions 6 and 7 in
      agonist and antagonist recognition of the human platelet P2Y(12)-receptor.
AB  - The P2Y(12)-receptor plays a prominent role in ADP-induced platelet aggregation.
      In the present study, we searched for amino acid residues involved in ligand
      recognition of the human P2Y(12)-receptor. Wild-type or mutated receptors were
      expressed in 1321N1 astrocytoma cells and Chinese hamster ovary (CHO) cells.
      There were no major differences in cellular expression of the constructs.
      Cellular cAMP production and cAMP response element (CRE)-dependent luciferase
      expression was increased by isoproterenol (astrocytoma cells) or forskolin (CHO
      cells). In cells expressing wild-type receptors, R256K or S101A mutant
      constructs, 2-methylthio-ADP inhibited the induced cAMP production with IC(50)
      concentrations of about 0.3nM. In cells expressing R256A constructs, the IC(50)
      concentration amounted to 25nM. In cells expressing H253A/R256A, Y259D and K280A
      constructs, 2-methylthio-ADP failed to affect the cellular cAMP production.
      Moreover, in cells expressing Y259D and K280A constructs, 2-methylthio-ADP did
      also not change the forskolin-induced CRE-dependent luciferase expression and
      caused only small increases in the serum response element-dependent luciferase
      expression. The antagonist cangrelor had similar potencies at wild-type receptors
      and R256A constructs (apparent pK(B)-value at wild-type receptors: 9.2). In
      contrast, reactive blue-2 had a lower potency at the R256A construct (apparent
      pK(B)-value at wild-type receptors: 7.6). In summary, the data indicate the
      involvement of Arg256, Tyr259 and, possibly, H253 (transmembrane region TM6) as
      well as Lys280 (TM7) in the function of the human P2Y(12)-receptor. Arg256
      appears to play a role in the recognition of nucleotide agonists and the non
      nucleotide antagonist reactive blue-2, but no role in the recognition of the
      nucleotide antagonist cangrelor.

PMID- 18809390
TI  - Assessment of anxiety-like behaviors in female rats bred for differences in
      kindling susceptibility and amygdala excitability.
AB  - Two rat lines bred for kindling susceptibility were previously observed to engage
      in different behavioral strategies in tests of emotionality. In order to extend
      past research on defensive behaviors in these strains which largely used males,
      Fast- and Slow-kindling females were assessed for anxiety-like behaviors in a
      number of aversive paradigms. Fast rats entered and spent more time in the open
      arms and spent less time in the closed arms of the elevated plus-maze (EPM)
      compared to Slow animals. Fast rats had higher conditioned suppression ratios
      across testing days, defecated less often during conditioning, and successfully
      disinhibited suppression during extinction in the conditioned emotional response
      (CER) paradigm compared to Slow-kindlers. In order to pursue these differences in
      emotional reactivity between the strains and differentiate negative affect from
      motivational, learning, and impulsive explanations, a separate group of animals
      were assessed in the light-enhanced acoustic startle chamber, a test of anxiety.
      When initially exposed to a bright-light, Slow rats significantly increased their
      startle response while this was not observed in the Fast strain. In combination
      with previous research on these strains, the present data tentatively suggest
      that Fast and Slow animals utilize different neural systems in tests of fear and
      anxiety which may have been co-selected with the direct selection of amygdala
      kindling susceptibility.

PMID- 18809391
TI  - The anabolic androgenic steroid nandrolone decanoate affects mRNA expression of
      dopaminergic but not serotonergic receptors.
AB  - The abuse of anabolic androgenic steroids (AASs) at supratherapeutic doses is a
      problem not only in the world of sports, but also among non-athletes using AASs
      to improve physical appearance and to become more bold and courageous.
      Investigations of the possible neurochemical effects of AAS have focused
      partially on the monoaminergic systems, which are involved in aggressive
      behaviours and the development of drug dependence. In the present study, we
      administered nandrolone decanoate (3 or 15 mg/kg/day for 14 days) and measured
      mRNA expression of dopaminergic and serotonergic receptors, transporters and
      enzymes in the male rat brain using quantitative real-time polymerase chain
      reaction. Expression of the dopamine D1-receptor transcript was elevated in the
      amygdala and decreased in the hippocampus while the transcript level of the
      dopamine D4-receptor was increased in the nucleus accumbens. No changes in
      transcriptional levels were detected among the serotonin-related genes examined
      in this study. The altered mRNA expression of the dopamine receptors may
      contribute to some of the behavioural changes often reported in AAS abusers of
      increased impulsivity, aggression and drug-seeking.

PMID- 18809392
TI  - Excitatory pathways from the vestibular nuclei to the NTS and the PBN and
      indirect vestibulo-cardiovascular pathway from the vestibular nuclei to the RVLM
      relayed by the NTS.
AB  - Previous studies have confirmed the existence of vestibulo-sympathetic pathways
      in the central nervous system. However, the exact pathways and neurotransmitters
      underlying this reflex are unclear. The present study was undertaken to
      investigate whether the vestibulo-cardiovascular responses are a result of
      activated glutamate receptors in the caudal vestibular nucleus. We also attempt
      to verify the indirect excitatory pathways from the vestibular nucleus (VN) to
      the rostral ventrolateral medulla (RVLM) using a tracing method combined with a
      vesicular glutamate transporter (VGluTs) immunofluorescence. In anesthetized
      rats, unilateral injection of l-glutamate (5 nmol) into the medial vestibular
      nucleus (MVe) and spinal vestibular nucleus (SpVe) slightly increased the mean
      arterial pressure (MVe: 93.29+/-11.58 to 96.30+/-11.66, SpVe: 91.72+/-15.20 to
      95.48+/-17.16). Local pretreatment with the N-methyl-D-aspartate (NMDA)-receptor
      antagonist MK-801 (2 nmol) significantly attenuated the pressor effect of L
      glutamate injected into the MVe compared to the contralateral self-control. After
      injection of biotinylated dextran amine (BDA) into the MVe and SpVe, and
      fluorogold (FG) into the RVLM, some BDA-labeled fibres and terminals in the
      nucleus of solitary tract (NTS) and the parabrachial nucleus (PBN) were
      immunoreactive for VGluT1 and VGluT2. Several BDA-labeled fibres were closely
      apposed to FG-labeled neurons in the NTS. These results suggested that activation
      of caudal vestibular nucleus neurons could induce pressor response and NMDA
      receptors might contribute to this response in the MVe. The glutamatergic VN-NTS
      and VN-PBN pathways might exist, and the projections from the VN to the RVLM
      relayed by the NTS comprise an indirect vestibulo-cardiovascular pathway in the
      brain stem.

PMID- 18809393
TI  - Dendritic spine density of posterodorsal medial amygdala neurons can be affected
      by gonadectomy and sex steroid manipulations in adult rats: a Golgi study.
AB  - The posterodorsal medial amygdala (MePD) is a sex steroid-responsive area in the
      rat brain. The dendritic spine density of Golgi-impregnated MePD neurons were
      studied in: (1) adult gonadectomized (GDX) males after a short or a longer
      postcastration period (8 and 90 days, respectively), compared to age-matched sham
      operated and to intact controls; (2) adult GDX females, which received oil,
      estradiol benzoate (EB) alone or EB and progesterone as substitutive therapy;
      and, (3) EB-treated GDX females that concomitantly received saline or LY235959, a
      competitive antagonist of NMDA receptors, to test a possible glutamatergic
      mediation on the estrogen-mediated increase in spine density in this brain area.
      Intact males showed a higher spine density than males studied 8 days after sham
      operation or those in both short- and long-term GDX groups (p<0.02), but not when
      compared to males at 90 days after sham operation (p=0.12). In females, dendritic
      spine density increased following EB injections when compared to the oil group
      (p=0.05), with an effect that was potentiated by progesterone (p<0.01). LY235959
      was not able to block the stimulating effect of EB on dendritic spines of GDX
      females (p>0.2). These data provide novel evidence that MePD dendritic spines are
      affected by sex steroid manipulations in adult rats, GDX males had a specific
      spine density decrease after a long postcastration period, and estrogen
      (apparently independently of a NMDA receptor interaction) and progesterone have
      stimulatory effects on the number of dendritic spines in GDX females.

PMID- 18809394
TI  - The binary phase behavior of 1,3-dicaproyl-2-stearoyl-sn-glycerol and 1,2
      dicaproyl-3-stearoyl-sn-glycerol.
AB  - The phase behavior of a binary system constituted of purified 1,3-dicaproyl-2
      stearoyl-sn-glycerol (CSC) and 1,2-dicaproyl-3-stearoyl-sn-glycerol (CCS) was
      investigated at a very slow (0.1 degrees C/min) and a relatively fast (3.0
      degrees C/min) cooling rate using differential scanning calorimetry (DSC), low
      resolution NMR, X-ray diffraction (XRD), and polarized light microscopy (PLM).
      Related forms of the beta' polymorph were detected for all mixtures as well as a
      beta form for CSC-rich mixtures. A double chain length (DCL) stacking of the non
      mixed CCS-CCS and CSC-CSC phases and a triple chain length (TCL) stacking of
      mixed CCS-CSC structure were detected for the different beta' forms. The kinetic
      phase diagram demonstrated an apparent eutectic at the 0.5(CSC) composition when
      cooled at 0.1 degrees C/min and at the 0.25(CSC) composition when cooled at 3.0
      degrees C/min. The application of a thermodynamic model based on the Hildebrand
      equation suggests that compounds CSC and CCS are not fully miscible. In addition,
      the miscibility changes according to the structure of the growing solid phase
      which is dependent on CSC molar ratio as well as on the kinetics. It was also
      shown that the miscibility is concentration dependent and that the solid phase,
      which is growing at conditions well away from equilibrium, is determined
      kinetically. The molecular interactions were found to be strong and to favor the
      formation of CSC-CCS pairs in the liquid state. CSC and CCS were also shown to be
      immiscible in the solid state. Depressions in solid fat content (SFC) were
      observed for both rates. Relatively complex networks made of needle-like,
      spherulitic and granular crystals were observed in the CSC/CCS system. A pure CSC
      phase was found to be instrumental in promoting a higher SFC, and more stable
      polymorphic forms. The microstructure was shown to be strongly dependent on the
      cooling rate and was linked to the different polymorphic forms observed by DSC
      and XRD. Correlations between SFC and the eutectic behavior have been observed
      for the 3.0 degrees C/min cooling rate, but not directly in the case of the 0.1
      degrees C/min cooling rate, where slower kinetics which favors the metastable to
      stable phase conversion processes prevented the same shifts in behavior.

PMID- 18809395
TI  - Gender-specific reference value of urine albumin-creatinine ratio in healthy
      Chinese adults: results of the Beijing CKD survey.
AB  - BACKGROUND: The reference value of urine albumin-creatinine ratio (ACR) has
      racial disparities. The ACR reference value in a healthy Beijing population is
      reported. METHODS: A reference Beijing population was sampled via a multistage,
      clustered complex sampling method. By excluding subjects with self-reported
      kidney disease, hypertension, diabetes, dyslipidemia, cardiovascular disease,
      obesity or underweight condition, overt proteinuria, hematuria, or pyuria, as
      well as those with an estimated glomerular filtration rate (eGFR) >
      200ml/min/1.73m2 or < 60ml/min/1.73m2, apparently healthy subjects (1260 males,
      2305 females, aged 18-84y) were selected to be included in the current analysis.
      Urine albumin was measured using the immunoturbidimetic method, creatinine was
      measured using Jaffe's kinetic method on a morning spot-urine sample, and ACR was
      calculated. The 95th percentile of ACR was used as the normal upper limit. The
      association between ACR and each of gender, age, systolic blood pressure, body
      mass index, serum glucose, lipids, and eGFR was examined. RESULTS: The normal
      upper limit of ACR was 14mg/g (1.58mg/mmol) for males and 20mg/g (2.26mg/mmol)
      for females. Females had higher ACR values than males, and age, systolic blood
      pressure, and eGFR were positively correlated with ACR. CONCLUSIONS: The ACR
      reference value in the healthy Beijing population is lower than that of the
      Western population. Age, systolic blood pressure, and eGFR were found to
      correlate with ACR.

PMID- 18809396
TI  - Cross-talk between integrins alpha1beta1 and alpha2beta1 in renal epithelial
      cells.
AB  - The collagen-binding integrins alpha1beta1 and alpha2beta1 have profoundly
      different functions, yet they are often co-expressed in epithelial cells. When
      both integrins are expressed in the same cell, it has been suggested that
      alpha1beta1 negatively regulates integrin alpha2beta1-dependent functions. In
      this study we utilized murine ureteric bud (UB) epithelial cells, which express
      no functionally detectable levels of endogenous integrins alpha1beta1 and
      alpha2beta1, to determine the mechanism whereby this regulation occurs. We
      demonstrate that UB cells expressing integrin alpha2beta1, but not alpha1beta1
      adhere, migrate and proliferate on collagen I as well as form cellular cords in
      3D collagen I gels. Substitution of the transmembrane domain of the integrin
      alpha2 subunit with that of alpha1 results in decreased cell adhesion, migration
      and cord formation. In contrast, substitution of the integrin alpha2 cytoplasmic
      tail with that of alpha1, decreases cell migration and cord formation, but
      increases proliferation. When integrin alpha1 and alpha2 subunits are co
      expressed in UB cells, the alpha1 subunit negatively regulates integrin
      alpha2beta1-dependent cord formation, adhesion and migration and this inhibition
      requires expression of both alpha1 and alpha2 tails. Thus, we provide evidence
      that the transmembrane and cytoplasmic domains of the alpha2 integrin subunit, as
      well as the alpha1 integrin subunit, regulate integrin alpha2beta1 cell function.

PMID- 18809397
TI  - Molecular pathology of pseudoexfoliation syndrome/glaucoma--new insights from
      LOXL1 gene associations.
AB  - Pseudoexfoliation (PEX) syndrome is a generalized disease of the extracellular
      matrix and a major cause of severe open-angle glaucoma. Single nucleotide
      polymorphisms (SNPs) in exon 1 of the lysyl oxidase-like 1 (LOXL1) gene have been
      recently identified as strong genetic risk factors for both PEX syndrome and PEX
      glaucoma. LOXL1 is a pivotal cross-linking enzyme in extracellular matrix
      metabolism and seems to be specifically required for elastic fiber formation and
      stabilization. This review outlines our current understanding of the role of
      LOXL1 in the pathophysiology of PEX syndrome and PEX glaucoma. The available data
      suggest that LOXL1 is differentially regulated dependent on the phase of
      progression of the fibrotic process. While increased levels of LOXL1 participate
      in the formation of abnormal PEX fiber aggregates in the initial phase of
      fibrogenesis, inadequate tissue levels may promote elastotic processes in
      advanced stages of the disease. Although the functional significance of LOXL1 in
      the specific PEX-associated matrix process still has to be determined,
      elucidation of the underlying molecular pathogenesis has been evolving, and might
      eventually open new approaches for specific treatment strategies in the future.

PMID- 18809398
TI  - Temporal changes in MMP mRNA expression in the lens epithelium during anterior
      subcapsular cataract formation.
AB  - Transforming growth factor beta (TGFbeta) has been known to play a role in
      anterior subcapsular cataract (ASC) formation and posterior capsule opacification
      (PCO), both of which are fibrotic pathologies of the lens. Several models have
      been utilized to study ASC formation, including the TGFbeta1 transgenic mouse
      model and the ex-vivo rat lens model. A distinct characteristic of ASC
      development within these models includes the formation of isolated fibrotic
      plaques or opacities which form beneath the lens capsule. A hallmark feature of
      ASC formation is the epithelial to mesenchymal transition (EMT) of lens
      epithelial cells (LECs) into myofibroblasts. Recently, the matrix
      metalloproteinases (MMPs) have been implicated in the formation of these
      cataracts through their involvement in EMT. In the present study, we sought to
      further investigate the role of MMPs in subcapsular cataract formation in a time
      course manner, through the examination of gene expression and morphological
      changes which occur during this process. RT-QPCR and immunohistochemical analysis
      was carried out on lenses treated with TGFbeta for a period of 2, 4 and 6 days.
      Laser capture microdissection (LCM) was utilized to specifically isolate cells
      within the plaque region and cells from the adjacent epithelium in lenses treated
      for a 6 day period. Multilayering of LECs was observed as early as day 2, which
      preceded the presence of alpha smooth muscle actin (alpha-SMA) immunoreactivity
      that was evident following 4 days of treatment with TGFbeta. A slight reduction
      in E-cadherin mRNA was detected at day 2, although this was not significant until
      the day 4 time point. Importantly, our results also indicate an early induction
      of MMP-9 mRNA following 2 days of TGFbeta treatment, whereas MMP-2 was found to
      be upregulated at the later 4 day time point. Further experiments using FHL 124
      cells show an induction in MMP-2 protein levels following treatment with
      recombinant MMP-9. Together these findings suggest an upstream role for MMP-9 in
      ASC formation.

PMID- 18809399
TI  - BALB/c and C57BL6 mouse strains vary in their ability to heal corneal epithelial
      debridement wounds.
AB  - Genetically engineered mice are usually produced on a mixed genetic background
      and can be derived from several mouse strains including 129SvJ, C57BL6, and
      BALB/c. To determine whether differences in recurrent corneal epithelial erosions
      (RCEEs), corneal epithelial stem cell deficiency (CESCD), and cell migration rate
      vary between two different mouse strains (BALB/c and C57BL6), 8-week mice were
      subjected to 1.5 (small) or 2.8mm (large) manual debridement wounds and allowed
      to heal for 4 weeks. Syndecan-1 (sdc-1) null mice backcrossed seven generations
      onto a BALB/c genetic background were also included in the RCEE and CESCD studies
      to permit comparisons between genotypes within a single strain. After sacrifice,
      corneas were assessed for the presence of recurrent erosions; no fewer than 15
      corneas were used for each strain or genotype studied. Data show that the
      frequency of recurrent erosions after small wounds was 81+/-9% in the C57BL6
      mice, 73+/-2% in the BALB/c mice, and 32+/-6% in sdc-1 null mice. Neither strain
      developed CESCD after small wounds. The frequency of erosions after large wounds
      was greater (88+/-8%) in the C57BL6 mice compared to BALB/c (60+/-2%), and sdc-1
      null mice (32+/-5%). Four weeks after the large wounds, fixed, flat mounted
      corneas were assessed for evidence of CESCD with antibodies against the
      conjunctival keratin K8 and the goblet cell marker, the mucin Muc5AC. The
      frequency of CESCD 4 weeks after the large wounds was significantly greater in
      the C57BL6 mice than in the BALB/c or sdc-1 null mice. To assess cell migration
      rates, corneas were subjected to 1.5mm wounds and allowed to heal for 12, 15, 18,
      21, and 24h. After sacrifice, corneas were stained with Richardson stain (BALB/c)
      or propidium iodide (C57BL6) to assess reepithelialization rates. While
      reepithelialization rates were similar for the early times after wounding, by 24h
      the C57BL6 corneas had healed faster: 16 of 30 corneas from the C57BL6 mice were
      closed compared to 9 of 30 of the BALB/c wounds. BALB/c corneas appeared larger
      overall compared to C57BL6 corneas; measurements of the overall mass of the
      enucleated eyes and diameters of the flat-mounted corneas confirmed that C57BL6
      eyes and corneas were 6.8% and 4.4% smaller respectively than those of BALB/c
      mice even though the masses of the two mouse strains at 8 weeks of age were
      identical. Using BrdU to label dividing cells, we found that 18 h after wounding,
      C57BL6 and BALB/c corneal epithelia showed similar numbers of proliferating
      cells. To determine if the enhanced corneal epithelial cell migration rate seen
      in the C57BL6 mice was specific to the cornea, we conducted time-lapse studies to
      assess random cell migration rates in vitro using primary cultures of mouse
      epidermal keratinocytes. Consistent with the in vivo data, epidermal
      keratinocytes derived from BALB/c mice migrated 60% slower than C57BL6 cells.
      These data prove that strain-specific differences in cell migration rate in vivo
      are present in the cornea and are accompanied by differences in the frequencies
      of recurrent erosions and corneal epithelial stem cell deficiency.

PMID- 18809400
TI  - Alpha-lipoic acid prevents mitochondrial damage and neurotoxicity in experimental
      chemotherapy neuropathy.
AB  - The study investigates if alpha-lipoic acid is neuroprotective against
      chemotherapy induced neurotoxicity, if mitochondrial damage plays a critical role
      in toxic neurodegenerative cascade, and if neuroprotective effects of alpha
      lipoic acid depend on mitochondria protection. We used an in vitro model of
      chemotherapy induced peripheral neuropathy that closely mimic the in vivo
      condition by exposing primary cultures of dorsal root ganglion (DRG) sensory
      neurons to paclitaxel and cisplatin, two widely used and highly effective
      chemotherapeutic drugs. This approach allowed investigating the efficacy of alpha
      lipoic acid in preventing axonal damage and apoptosis and the function and
      ultrastructural morphology of mitochondria after exposure to toxic agents and
      alpha-lipoic acid. Our results demonstrate that both cisplatin and paclitaxel
      cause early mitochondrial impairment with loss of membrane potential and
      induction of autophagic vacuoles in neurons. Alpha-lipoic acid exerts
      neuroprotective effects against chemotherapy induced neurotoxicity in sensory
      neurons: it rescues the mitochondrial toxicity and induces the expression of
      frataxin, an essential mitochondrial protein with anti-oxidant and chaperone
      properties. In conclusion mitochondrial toxicity is an early common event both in
      paclitaxel and cisplatin induced neurotoxicity. Alpha-lipoic acid protects
      sensory neurons through its anti-oxidant and mitochondrial regulatory functions,
      possibly inducing the expression of frataxin. These findings suggest that alpha
      lipoic acid might reduce the risk of developing peripheral nerve toxicity in
      patients undergoing chemotherapy and encourage further confirmatory clinical
      trials.

PMID- 18809401
TI  - Expression of defensin, cecropin, and transferrin in Aedes aegypti (Diptera:
      Culicidae) infected with Wuchereria bancrofti (Spirurida: Onchocercidae), and the
      abnormal development of nematodes in the mosquito.
AB  - The temporal expression of defensin, cecropin and transferrin was assessed in
      Aedes aegypti naturally refractory to Wuchereria bancrofti upon infection with
      this worm, in parallel to analysis of filarial development in the insect.
      Compared to controls, transcription of defensin and cecropin was higher in
      infected mosquitoes as soon as 2h post infection and peaked before 48h.
      Transferrin transcription was higher in infected mosquitoes at 24h, and at 48h
      was almost leveled to controls. At 72h and 7 days post infection, levels of all
      transcripts in infected insects decreased gradually and were similar to controls
      in most cases. Worm development in A. aegypti was visually abnormal from the
      beginning of infection. Here, we report, for the first time, the up-regulation of
      endogenous immune molecules in A. aegypti infected with W. bancrofti and provide
      a description of the worm development inside the insect. The specificities of A.
      aegypti-W. bancrofti model compared to other mosquito-filaria systems are
      discussed.

PMID- 18809402
TI  - Plasmodium relictum (lineage P-SGS1): effects on experimentally infected
      passerine birds.
AB  - We evaluated the effects of Plasmodium relictum (lineage P-SGS1), which is a host
      generalist, to five species of passerine birds. Light infection of P. relictum
      was isolated from a naturally infected adult reed warbler Acrocephalus
      scirpaceus. The parasites were inoculated to naive juveniles of the chaffinch
      Fringilla coelebs, common crossbill Loxia curvirostra, house sparrow Passer
      domesticus, siskin Spinus spinus and starling Sturnus vulgaris. Susceptibility of
      these birds to the infection of P. relictum was markedly different. This parasite
      developed in birds belonging to the Fringillidae and Passeridae but the starlings
      (Sturnidae) were resistant. Only 50% of experimental house sparrows were
      susceptible to the infection. The intensity of parasitemia varied markedly inside
      and between different susceptible bird species. There were no effects of the
      infection on body mass or temperature of experimentally infected birds. Infection
      of P. relictum leads to the significant decrease of haematocrit value and
      hypertrophy of spleen and liver in heavily infected common crossbills and
      siskins. This study shows that infection of the same lineage of P. relictum
      causes diseases of different severity in different avian hosts; that might have
      different evolutionary consequences and should be taken in consideration in
      conservation projects.

PMID- 18809403
TI  - Leishmania infantum: provision of reducing equivalents to the mitochondrial
      tryparedoxin/tryparedoxin peroxidase system.
AB  - Within the mitochondrion of Leishmania infantum, hydroperoxide metabolism relies
      on the activity of tryparedoxin-dependent peroxidases (TXNPxs). Tryparedoxins
      (TXNs) are thioredoxin-related oxidoreductases, which in vitro are reduced by the
      trypanothione reductase/trypanothione [TR/T(SH)(2)] redox couple. Still, there is
      no evidence that this actually occurs in the mitochondrion. This communication
      addresses the question of how the mitochondrial TXN/TXNPx system is reduced.
      First, using a digitonin fractionation assay, we show that TR activity is absent
      from the L. infantum mitochondrion. The possibility that this organelle possesses
      alternative electron sources for TXN/TXNPx is then investigated. Biochemical
      assays performed with purified recombinant enzymes, revealed that TR and T(SH)(2)
      can be replaced, albeit less efficiently, by the dihydrolipoamide
      dehydrogenase/lipoamide redox system as TXN/TXNPx electron donor. This result
      challenges the classical view that T(SH)(2) is the only reductant for TXNs and
      add new prospects regarding the involvement of 2-oxo acid dehydrogenase complexes
      in L. infantum mitochondrial hydroperoxide metabolism.

PMID- 18809404
TI  - Glucagon receptor signaling is essential for control of murine hepatocyte
      survival.
AB  - BACKGROUND & AIMS: Glucagon action in the liver is essential for control of
      glucose homeostasis and the counterregulatory response to hypoglycemia. Because
      receptors for the related peptides glucagon-like peptide-1 and glucagon-like
      peptide-2 regulate beta-cell and enterocyte apoptosis, respectively, we examined
      whether glucagon receptor (Gcgr) signaling modulates hepatocyte survival.
      METHODS: The importance of the Gcgr for hepatocyte cell survival was examined
      using Gcgr+/+ and Gcgr-/- mice in vivo, and murine hepatocyte cultures in vitro.
      RESULTS: Gcgr-/- mice showed enhanced susceptibility to experimental liver injury
      induced by either Fas Ligord activation or a methionine- and choline-deficient
      diet. Restoration of hepatic Gcgr expression in Gcgr-/- mice attenuated the
      development of hepatocellular injury. Furthermore, exogenous glucagon
      administration reduced Jo2-induced apoptosis in wild-type mice and decreased
      caspase activation in fibroblasts expressing a heterologous Gcgr and in primary
      murine hepatocyte cultures. The anti-apoptotic actions of glucagon were
      independent of protein kinase A, phosphatidylinositol-3K, and mitogen-activated
      protein kinase, and were mimicked by the exchange protein directly activated by
      the cyclic AMP agonist 8-(4-chloro-phenylthio)-2'-O-methyladenosine-3', 5'-cyclic
      monophosphate-cAMP. CONCLUSIONS: These findings extend the essential actions of
      the Gcgr beyond the metabolic control of glucose homeostasis to encompass the
      regulation of hepatocyte survival.

PMID- 18809405
TI  - Changes in GnRH I, bradykinin and their receptors and GnIH in the ovary of
      Calotes versicolor during reproductive cycle.
AB  - The aim of this study was to investigate changes in the abundance of
      gonadotrophin releasing hormone I (GnRH I) and GnRH I receptor in the ovary of
      Calotes versicolor during the reproductive cycle and correlate them with the
      changes in gonadotrophin inhibitory hormone (GnIH), bradykinin and bradykinin
      B(2) receptor in order to understand their interaction during ovarian cycle. GnRH
      I, bradykinin and their receptors and GnIH, were localized immunohistochemically
      in the ovary. Relative intensity of these peptides was estimated from the
      contralateral ovary using slot/Western blot followed by densitometry. The
      immunostaining of GnRH I, bradykinin and their receptors and GnIH were localized
      in the granulosa cells of previtellogenic follicles and stroma cells, whereas in
      the peripheral part of the cytoplasm in oocytes of vitellogenic and ovulatory
      follicles. The GnRH I immunostaining was relatively higher in inactive phase, but
      was low during active preovulatory phase suggesting inverse correlation with
      circulating estradiol level. The study showed a positive correlation between the
      expression pattern of GnRH I and GnIH, but showed a negative correlation between
      GnIH with GnRH I receptor in the ovary. This study further suggests a possibility
      for bradykinin regulating GnRH I synthesis in the ovary. An increase in the
      immunostaining of both GnRH I and GnIH in the oocyte prior to ovulation suggests
      their involvement in the oocyte maturation. It is thus concluded that the ovary
      of C. versicolor possesses GnRH I-GnIH-bradykinin system and interaction between
      these neuropeptides may be involved in the regulation of follicular development
      and oocyte maturation.

PMID- 18809406
TI  - The interactive effect of the cholinergic system and acute ovarian suppression on
      the brain: an fMRI study.
AB  - Recent evidence suggests that loss of ovarian function following ovariectomy is a
      risk factor for Alzheimer's disease (AD); however, the biological basis of this
      risk remains poorly understood. We carried out an fMRI study into the interaction
      between loss of ovarian function (after Gonadotropin Hormone Releasing Hormone
      agonist (GnRHa) treatment) and scopolamine (a cholinergic antagonist used to
      model the memory decline associated with aging and AD). Behaviorally, cholinergic
      depletion produced a deficit in verbal recognition performance in both GnRHa
      treated women and wait list controls, but only GnRHa-treated women made more
      false positive errors with cholinergic depletion. Similarly, cholinergic
      depletion produced a decrease in activation in the left inferior frontal gyrus
      (LIFG; Brodmann area 45)--a brain region implicated in retrieving word meaning-
      in both groups, and activation in this area was further reduced following GnRHa
      treatment. These findings suggest biological mechanisms through which ovarian
      hormone suppression may interact with the cholinergic system and the LIFG.
      Furthermore, this interaction may provide a useful model to help explain reports
      of increased risk for cognitive decline and AD in women following ovariectomy.

PMID- 18809407
TI  - Gonadal hormones modulate sex differences in judgments of relative numerousness
      in meadow voles, Microtus pennsylvanicus.
AB  - Animals in a variety of taxa discriminate between a greater quantity and a lesser
      quantity of the same object, an ability that is referred to as relative
      numerousness judgment. For example, meadow voles can distinguish between areas
      containing more over-marks by one opposite-sex scent donor and fewer over-marks
      by another opposite-sex scent donor. Females appear to be able to make better
      discriminations between more or less over-marks than do males. In that gonadal
      hormones have been implicated in modulating cognitive function associated with
      spatial tasks, we tested the hypothesis that high titers of testosterone and
      estradiol are necessary for male and female voles, respectively, to distinguish
      between the top- and bottom-scent donors in an area containing mixed over-marks.
      We gonadectomized voles, giving them either gonadal hormone replacement
      (testosterone for males and estradiol for females) or no hormone replacement, and
      tested their spontaneous judgments of distinguishing between the top- and bottom
      scent donors in an area containing mixed over-marks; a task involving judgments
      of relative numerousness. Female voles given replacement estradiol performed
      better than did female voles not given replacement estradiol in determining the
      top-scent and bottom-scent males in areas containing mixed over-marks. In
      contrast, males not treated with replacement testosterone performed better than
      did males treated with testosterone in determining the top-scent and bottom-scent
      males in areas containing mixed over-marks. Thus, high titers of estradiol and
      low titers of testosterone are associated with better performance on tasks
      involving relative numerousness in female and male voles, respectively. The
      results of this task on relative numerousness judgments are discussed in relation
      to the effects of gonadal steroid hormone on spatial ability, a closely related
      cognitive domain, and the social biology of meadow voles.

PMID- 18809408
TI  - Effects of a microsporidium from the convergent lady beetle, Hippodamia
      convergens Guerin-Meneville (Coleoptera: Coccinellidae), on three non-target
      coccinellids.
AB  - A microsporidium from Hippodamia convergens was transmitted horizontally to three
      non-target coccinellid hosts (Adalia bipunctata L., Coccinella septempunctata L.
      and Harmonia axyridis Pallas) under laboratory conditions. For all species
      examined, microsporidia-infected larvae took significantly longer to develop than
      did uninfected larvae but the microsporidium had no effect on larval mortality.
      Adult sex ratios of uninfected and microsporidia-infected adults were about 1:1
      (female symbol:male symbol) and did not differ significantly. At the end of a 90
      day trial, microsporidia-infected H. convergens produced significantly fewer eggs
      and did not live as long as uninfected individuals. Differences in fecundity and
      longevity were not observed for the three non-target coccinellids that were
      examined. Mean spore counts from smear preparations of microsporidia-infected A.
      bipunctata did not differ significantly from H. convergens, suggesting that A.
      bipunctata (a native coccinellid) is a suitable host for the microsporidium but
      infection was lighter in C. septempunctata and H. axyridis (introduced species).
      Vertical transmission of the pathogen was observed during the 90-day trial by
      examining eggs and larvae that were produced by microsporidia-infected adults.
      For all species examined, 100% vertical transmission of the pathogen was
      eventually observed. Three eugregarines were found in two adult A. bipunctata:
      Gregarine A trophozoites are similar in size to those of Gregarina katherina
      Watson (described earlier from Coccinella spp.), Gregarine B trophozoites are
      similar in size to those of Gregarine A but are morphology distinct, and
      Gregarine C trophozoites are similar in size to G. barbarara Watson (described
      earlier from A. bipunctata).

PMID- 18809409
TI  - Characterization of bacterial symbionts in Frankliniella occidentalis (Pergande),
      Western flower thrips.
AB  - Many insects have associations with bacteria, although it is often difficult to
      determine the intricacies of the relationships. In one such case, facultative
      bacteria have been discovered in a major crop pest and virus vector, the Western
      flower thrips (WFT), Frankliniella occidentalis (Pergande) (Thysanoptera:
      Thripidae). Several bacterial isolates have been studied in Netherlands
      greenhouse thrips populations, with molecular data indicating that these bacteria
      were similar to Escherichia coli, although biochemical properties suggested these
      microbes might actually be most similar to plant pathogenic bacteria in the genus
      Erwinia. We focused on the bacterial flora of the Hawaiian Islands thrips
      population where these gut bacteria were first reported in 1989. We also analyzed
      a German population and a 1965 California population preserved in ethanol.
      Culture and culture-independent techniques revealed a consistent microflora that
      was similar to the Netherlands isolates studied. The similarity among thrips
      microbes from multiple populations and environments suggested these bacteria and
      their hosts share a widespread association. Molecular phylogeny based on the 16S
      rRNA gene and biochemical analysis of thrips bacteria suggested two distinctive
      groups of microbes are present in thrips. Phylogenetic analysis also revealed
      support for one thrips bacterial group having a shared ancestry with Erwinia,
      whereas the second group of thrips bacteria fell out with E. coli, but without
      support. Although species-specific relationships were indeterminable due to the
      conservative nature of 16S, there is strong indication that thrips symbionts
      belong to two different genera and originated from environmental microbes.

PMID- 18809410
TI  - Generation, affinity maturation, and characterization of a human anti-human NKG2D
      monoclonal antibody with dual antagonistic and agonistic activity.
AB  - In humans, NKG2D is an activating receptor on natural killer (NK) cells and a
      costimulatory receptor on certain T cells and plays a central role in mediating
      immune responses in autoimmune diseases, infectious diseases, and cancer.
      Monoclonal antibodies that antagonize or agonize immune responses mediated by
      human NKG2D are considered to be of broad and potent therapeutic utility.
      Nonetheless, monoclonal antibodies to NKG2D that are suitable for clinical
      investigations have not been published yet. Here, we describe the generation,
      affinity maturation, and characterization of a fully human monoclonal antibody to
      human NKG2D. Using phage display technology based on a newly generated naive
      human Fab library in phage display vector pC3C followed by a tandem chain
      shuffling process designed for minimal deviation from natural human antibody
      sequences, we selected a human Fab, designated KYK-2.0, with high specificity and
      affinity to human NKG2D. KYK-2.0 Fab blocked the binding of the natural human
      NKG2D ligands MICA, MICB, and ULBP2 as potently as a commercially available mouse
      anti-human NKG2D monoclonal antibody in immunoglobulin G (IgG) format. Conversion
      of KYK-2.0 Fab to IgG1 resulted in subnanomolar avidity for human NKG2D. KYK-2.0
      IgG1 was found to selectively recognize defined subpopulations of human
      lymphocytes known to express NKG2D, that is, the majority of human CD8+, CD16+,
      and CD56+ cells as well as a small fraction of human CD4+ cells. In solution, KYK
      2.0 IgG1 interfered with the cytolytic activity of ex vivo expanded human NK
      cells. By contrast, immobilized KYK-2.0 IgG1 was found to strongly induce human
      NK cell activation. The dual antagonistic and agonistic activity promises a wide
      range of therapeutic applications for KYK-2.0 IgG1 and its derivatives.

PMID- 18809411
TI  - Mutational analysis of the aggregation-prone and disaggregation-prone regions of
      acylphosphatase.
AB  - We have performed an extensive mutational analysis of aggregation and
      disaggregation of amyloid-like protofibrils of human muscle acylphosphatase. Our
      findings indicate that the regions that promote aggregation in 25% (v/v) 2,2,2
      trifluoroethanol (TFE) are different from those that promote disaggregation under
      milder conditions (5% TFE). Significant changes in the rate of disaggregation of
      protofibrils in 5% TFE result not only from mutations situated in the regions of
      the sequence that play a key role in the mechanism of aggregation in 25% TFE, but
      also from mutations located in other regions. In order to rationalise these
      results, we have used a modified version of the Zyggregator aggregation
      propensity prediction algorithm to take into account structural rearrangements of
      the protofibrils that may be induced by changes in solution conditions. Our
      results suggest that a wider range of residues contributes to the stability of
      the aggregates in addition to those that play an important kinetic role in the
      aggregation process. The mutational approach described here is capable of
      providing residue-specific information on the structure and dynamics of amyloid
      protofibrils under conditions close to physiological and should be widely
      applicable to other systems.

PMID- 18809412
TI  - Intrinsically unstructured domains of Arf and Hdm2 form bimolecular oligomeric
      structures in vitro and in vivo.
AB  - Arf, Hdm2, and p53 regulate the tumor-suppressor pathway that is most frequently
      disrupted in human cancer. In the absence of tumorigenic stress, Hdm2 actively
      attenuates p53-dependent cell cycle arrest and apoptosis by mediating
      ubiquitination-dependent degradation of p53. Mitogenic stress activates Arf,
      which indirectly activates p53 by binding to and nullifying the anti-p53
      activities of Hdm2. Small conserved domains within Arf and Hdm2 mediate their
      direct interaction. Individually, these domains are intrinsically unstructured
      and, when combined in vitro, cofold into bimolecular oligomeric structures that
      resemble amyloid fibrils in some features. Detailed structural characterization
      of Hdm2/Arf complexes has previously been hampered by their heterogeneity and
      large size. Here, we report that a nine-residue fragment of the N-terminus of
      mouse Arf (termed "A1-mini") cofolds specifically with the Arf-binding domain of
      Hdm2 to form bimolecular oligomers. We characterized these unprecedented
      structures using analytical ultracentrifugation and NMR spectroscopy, providing
      insights into their structural organization. The A1-mini peptide not only binds
      specifically to Hdm2 in vitro but also recapitulates the nucleolar localization
      features of full-length Arf in cells. Furthermore, larger fragments of Arf that
      contain the A1-mini segment have previously been shown to activate p53 in mouse
      and human cells. Our studies provide the first insights into the molecular basis
      through which Arf nullifies the p53-inhibiting activity of Hdm2, indirectly
      activating the tumor-suppressor function of p53 in mammalian cells.

PMID- 18809413
TI  - Effects of oral consumption of the green tea polyphenol EGCG in a murine model
      for human Sjogren's syndrome, an autoimmune disease.
AB  - SIGNIFICANCE: Protection of glandular cells from autoimmune-induced damage would
      be of significant clinical benefit to Sjogren's syndrome (SS) patients.
      Epigallocatechin-3-gallate (EGCG) possesses anti-apoptotic, anti-inflammatory,
      and autoantigen-inhibitory properties. AIMS: To investigate if EGCG protects
      against certain autoimmune-induced pathological changes in the salivary glands of
      the non-obese diabetic (NOD) mouse model for SS. MAIN METHODS: Animals were
      provided with either water or water containing 0.2% EGCG. At the age of 8, 16 and
      22 weeks, submandibular salivary gland tissue and serum samples were collected
      for pathological and serological analysis. KEY FINDINGS: Significant lymphocyte
      infiltration was observed in the salivary glands of the water-fed group at the
      age of 16 weeks, while the EGCG group showed reduced lymphocyte infiltration. By
      22 weeks of age, water-fed animals demonstrated elevated levels of apoptotic
      activity within the lymphocytic infiltrates, and high levels of serum total anti
      nuclear antibody, compared to EGCG-fed animals. Remarkably, proliferating cell
      nuclear antigen (PCNA) and Ki-67 levels in the salivary glands of water-fed NOD
      mice were significantly elevated in comparison to BALB/c control mice; in
      contrast, PCNA and Ki-67 levels in EGCG-fed NOD animals were similar to BALB/c
      mice. These results indicate that EGCG protects the NOD mouse submandibular
      glands from autoimmune-induced inflammation, and reduces serum autoantibody
      levels. Abnormal proliferation, rather than apoptosis, appears to be a
      characteristic of the NOD mouse gland that is normalized by EGCG. The evidence
      suggests that EGCG could be useful in delaying or managing SS-like autoimmune
      disorders.

PMID- 18809414
TI  - Measuring interstitial fluid pressure with fiberoptic pressure transducers.
AB  - In this report we describe a practical procedure for measuring interstitial fluid
      pressure (IFP) using fiberoptic pressure transducers based on optical
      interferometry. Eight mice were used for subcutaneous IFP measurements and four
      mice for intramuscular IFP measurements with a FOBPS-18 fiberoptic pressure
      transducer. We used four mice for subcutaneous IFP measurements with a SAMBA-420
      MR fiberoptic pressure transducer. One measurement was made for each mouse
      simultaneously by using a fiberoptic system and an established approach, either
      transducer-tipped catheter or wick-in-needle technique. The mean IFP values
      obtained in subcutaneous tissues were -3.00 mm Hg (SEM-/+0.462, n=8), -3.25 mm Hg
      (SEM-/+0.478, n=4), -3.34 mm Hg (SEM-/+0.312, n=6), and -2.85 (SEM-/+0.57, n=6)
      for the FOBPS fiberoptic transducer, the SAMBA fiberoptic transducer, the
      transducer-tipped catheter, and the wick-in-needle technique, respectively. There
      was no difference between these techniques to measure IFP (Friedman test,
      p=0.7997). The subcutaneous IFP measurements showed strong linear correlation
      between fiberoptic transducer and transducer-tipped catheter (R(2)=0.9950) and
      fiberoptic transducer and wick-in-needle technique (R(2)=0.9966). Fiberoptic
      pressure transducers measure the interstitial fluid pressure accurately,
      comparable to conventional techniques. The simplified IFP measurement procedures
      described in this report will allow investigators to easily measure IFP, and
      elucidate the unit pressure change per unit volume change (dP/dV) in normal or
      cancer tissues in the presence of strong electromagnetic fields encountered in
      MRI.

PMID- 18809415
TI  - WAY100635 prevents the changes induced by fluoxetine upon the 5-HT1A receptor
      functionality.
AB  - 5-HT1A receptor-mediated signalling in rat brain was evaluated after chronic
      administration (14 days; s.c.) of the selective serotonin reuptake inhibitor
      (SRRI) fluoxetine (10 mg/kg/day) alone, or in combination with the 5-HT1A
      receptor antagonist WAY100635 (0.1 mg/kg/day). The density of 5-HT1A binding
      sites was unchanged following fluoxetine, WAY100635, or the combination of
      fluoxetine and WAY100635. However, the net stimulation of [35S]GTPgammaS binding
      induced by the 5-HT1A agonist 8-OH-DPAT was significantly attenuated in dorsal
      raphe nucleus (DRN), but not in hippocampus, after chronic fluoxetine. Moreover,
      depending of the area analysed, the basal binding of [35S]GTPgammaS was
      differentially affected by this treatment: increased in DRN and decreased in
      hippocampal dentate gyrus. Interestingly, the changes in [35S]GTPgammaS basal
      binding and on 5-HT1A receptors functionality were prevented by the concomitant
      administration of WAY100635. The inhibition of dorsal raphe firing by 8-OH-DPAT
      was also attenuated in fluoxetine-treated rats (ED50 = 2.12 +/- 0.32 microg/kg
      and 4.34 +/- 0.09 microg/kg, for vehicle and fluoxetine respectively), an effect
      which was also prevented by the concomitant administration of WAY100635 (ED50 =
      2.10 +/- 0.58 microg/kg). Chronic administration of WAY100635 alone did not
      affect the 5-HT1A receptor-induced stimulation of [35S]GTPgammaS binding, nor the
      8-OH-DPAT-induced inhibition of 5-HT neuron firing. These results demonstrate
      that the concomitant blockade of 5-HT1A receptors when administering fluoxetine
      prevents those adaptive changes of 5-HT1A receptor function associated with the
      chronic administration of this antidepressant. These findings could be relevant
      from the therapeutic point of view, and further support the potential benefit of
      treatments with a SSRI/5-HT1A receptor antagonist combination.

PMID- 18809416
TI  - Phosphorylation of TRPV1 by neurokinin-1 receptor agonist exaggerates the
      capsaicin-mediated substance P release from cultured rat dorsal root ganglion
      neurons.
AB  - The present study was conducted to determine whether the activation of neurokinin
      1 receptor (NK-1R) by its agonist (GR73632) enhances the capsaicin-evoked
      substance P (SP) release using a radioimmunoassay. A pre-exposure to GR73632
      enhanced the capsaicin-evoked SP release in a time- and dose-dependent manner.
      The augmentation of capsaicin-evoked SP release by GR73632 was completely
      inhibited by pharmacological blockade of NK-1R or transient receptor potential
      vanilloid receptor subtype 1 (TRPV1), and was partially attenuated by the
      inhibition of either protein kinase C (PKC), cyclooxygenase (COX) or
      phospholipase C (PLC), p38 or p42/44 mitogen-activated protein (MAP) kinase, but
      not protein kinase A. This augmentation of SP release was further increased by
      inhibition of c-Jun NH2-terminal kinase. A short-term (10min) exposure to GR73632
      resulted in an increase in the TRPV1 phosphorylation. The increase in the TRPV1
      phosphorylated forms induced by a 60-min exposure to GR73632 was completely
      abolished by the inhibition of either PKC, COX or PLC, p38 or p42/44 MAP kinases.
      Immunocytochemistry study demonstrated that the NK-1R and TRPV1 were mainly co
      expressed in the small-sized neurons. These findings suggest that the activation
      of NK-1R by its agonist, by sensitizing the TRPV1 through the PKC phosphorylation
      of TRPV1, may play a role in the enhancement of the capsaicin-evoked SP release
      from cultured rat DRG neurons.

PMID- 18809417
TI  - The motivation to obtain nicotine-conditioned reinforcers depends on nicotine
      dose.
AB  - Stimuli associated with nicotine (NIC) can acquire new meaning via Pavlovian
      conditioning. If a stimulus is associated with the primary reinforcing effects of
      NIC, the new conditional properties of the stimulus should make it a more
      valuable reinforcer (i.e., increase the motivation to obtain the stimulus), and
      this value should be based, in part, on the strength or intensity of the primary
      reinforcer (i.e., NIC dose). The purpose of the present study was to investigate
      whether NIC-conditioned reinforcement increased motivation to obtain non-NIC
      stimuli, as reflected by performance on a progressive ratio (PR) reinforcement
      schedule, and whether this increased motivation was systematically related to NIC
      dose. Two Paired groups were allowed to nose-poke for NIC (0.03 or
      0.09mg/kg/infusion, IV) accompanied by 15-s illumination of a stimulus light
      (conditional stimulus or CS). Two Unpaired groups (0.03 or 0.09mg/kg/infusion)
      could also make a nose-poke response for the CS; however their NIC infusions were
      controlled by the Paired group (i.e., yoked design). A fifth group (CS-Only) was
      allowed to nose-poke for CS presentations and saline infusions. After 29
      conditioning sessions the nose-poke operant was prevented by obscuring the
      receptacle and the CS (accompanied by saline infusion for all groups) was made
      contingent upon a novel operant response (lever press). During the acquisition of
      this novel response, each CS/saline infusion earned increased the number of
      responses required to earn the next CS/saline infusion. Pairings with the primary
      reinforcing effects of NIC resulted the acquisition of a novel response for the
      CS. Motivation to obtain the CS depended on salience (dose) of the primary
      reinforcement (NIC).

PMID- 18809418
TI  - Region-specific changes in 5-HT1A agonist-induced Extracellular signal-Regulated
      Kinases 1/2 phosphorylation in rat brain: a quantitative ELISA study.
AB  - Brain serotonin 5-HT(1A) receptor, a traditional target for the treatment of mood
      disorders, modulates intracellular signalling pathways, such as the Extracellular
      signal-Regulated Kinases 1/2 (ERK1/2) pathway. The present studies are the first
      to determine levels of phospho-ERK1/2 (pERK1/2) in brain using a quantitative
      Enzyme Linked-Immuno-Sorbent Assay. We examined pERK1/2 levels in rat brain
      following administration of (+)8-OH-DPAT, buspirone as well as of the more
      selective, high-efficacy 5-HT(1A) agonists F13640 and F13714. Intraperitoneal
      injection of these compounds increased pERK1/2 in prefrontal cortex and
      hypothalamus, with a maximum at 5-15min and a significant effect lasting until 30
      60min post-injection. However, these compounds reduced hippocampal pERK1/2 with a
      maximum effect at 30min, persisting until 60min post-injection. In hippocampus,
      F13640, F13714 and buspirone inhibited pERK1/2 in a dose-dependent manner as of
      0.04, 0.04 and 2.5mg/kg, respectively. Given these low doses, this response is
      likely related to activation of sensitive presynaptic 5-HT(1A) receptors in the
      raphe nucleus. 4- and 16-fold higher doses of these compounds were necessary to
      stimulate pERK1/2 in prefrontal cortex and hypothalamus, respectively, via direct
      5-HT(1A) receptor activation. In contrast, (+)8-OH-DPAT was active at similar
      doses (0.63mg/kg) in these different regions. Pretreatment with the 5-HT(1A)
      antagonist, WAY100635, completely blocked the effects of these compounds, with
      the exception of buspirone-induced pERK1/2 increases in hypothalamus. Thus, 5
      HT(1A) agonist-induced changes in pERK1/2 in rat brain are time- and dose
      dependent and region-specific. Furthermore, F13640, F13714, buspirone, but not
      (+)8-OH-DPAT, exert their effects via preferential activation of presynaptic 5
      HT(1A) receptors.

PMID- 18809419
TI  - In vivo seizure induction and pharmacological preconditioning by domoic acid and
      isodomoic acids A, B and C.
AB  - To date, nothing is known of the pharmacological properties of isomers of domoic
      acid (DA) in vivo in mammals. Here we assessed the acute seizurogenic and toxic
      properties of DA, isodomoic acids A, B and C (Iso-A, -B, -C), and the therapeutic
      potential of these compounds as pharmacological preconditioning agents. DA, Iso
      A, Iso-B, and Iso-C all produced significant dose-dependent increases in seizure
      activity following intrahippocampal administration; doses producing half maximal
      cumulative seizure scores (ED50) were 137 pmol, 171 pmol, 13,000 pmol, and 3150
      pmol, respectively. Pharmacological preconditioning with low-dose DA or Iso-A, 60
      min before a high test dose of DA produced a significant reduction in seizure
      scores. In contrast, Iso-B and Iso-C each failed to induce any detectable
      tolerance to high-dose DA. Radioligand binding indicated a significant
      correlation between seizurogenic potency and kainate receptor affinity with KIs
      of 2.4 nM, 4.4 nM, 4990 nM and 170 nM for DA, Iso-A, Iso-B and Iso-C,
      respectively. Our in vivo results indicate that DA and Iso-A are functionally
      equipotent in acute seizure induction by direct intrahippocampal administration,
      while Iso-B and Iso-C are distinctly less potent.

PMID- 18809420
TI  - Auditory gating in rat hippocampus and medial prefrontal cortex: effect of the
      cannabinoid agonist WIN55,212-2.
AB  - Sensory gating can be assessed in rodents and humans using an auditory
      conditioning (C)-test (T) paradigm, with schizophrenic patients exhibiting a loss
      of gating. Dysregulation of the endocannabinoid system has been proposed to be
      involved in the pathogenesis of schizophrenia. We studied auditory gating and the
      effects of the cannabinoid agonist WIN55,212-22 on gating in CA3 and dentate
      gyrus (DG) of the hippocampus and medial prefrontal cortex (mPFC) in male Lister
      hooded rats using in vivo electrophysiology. The effects of a single dose of
      WIN55,212-2 on the N2 local field potential (LFP) test/conditioning amplitude
      ratios (T/C ratio) and response latencies were examined. In rats that
      demonstrated gating of N2, mPFC showed higher T/C ratios and shorter conditioning
      response latencies compared to DG and CA3. WIN55,212-2 disrupted auditory gating
      in all three areas with a significant increase in test amplitudes in the gating
      rats. A group of non-gating rats demonstrated higher test amplitudes and higher
      T/C ratios compared to gating rats. WIN55,212-2 had no effect on T/C ratios in
      the non-gating rats. The cannabinoid receptor (CB1) antagonist SR141716A
      prevented WIN55,212-2 induced disruption of gating. This study demonstrates gated
      auditory-evoked responses in CA3, DG and mPFC. The mPFC showed an early phase of
      gating which may later be modulated by CA3 and DG activity. Furthermore,
      cannabinoid receptor activation disrupted auditory gating in CA3, DG and mPFC, an
      effect which was prevented by CB1 receptor antagonism. The results further
      demonstrate the presence of a non-gating rat population which responded
      differently to cannabinoid agonists.

PMID- 18809421
TI  - Rutaecarpine inhibits hypoxia/reoxygenation-induced apoptosis in rat hippocampal
      neurons.
AB  - Our previous studies showed that rutaecarpine (Rut) protected against myocardial
      ischemia/reperfusion (I/R) injury, which was associated with activation of
      transient receptor potential vanilloid subtype 1 (TRPV1). Recently, TRPV1
      activation was also reported to exert neuroprotective effects. The present study
      was to investigate the effect of Rut on hypoxia/reoxygenation (H/R)-induced
      apoptosis in primary rat hippocampal neurons. Three-hour hypoxia (1% O2) and
      consequent 24-h reoxygenation significantly increased the apoptotic death of
      hippocampal neurons as evidenced by increases in both TUNEL-positive cell number
      and caspase-3 activity. However, pretreatment with Rut (1-10microM) or caspase-3
      specific inhibitor DEVD-CHO could markedly attenuate H/R-induced apoptosis in
      neurons. Rut markedly induced the phosphorylation of Akt and PI3K inhibitor
      LY294002 prevented the survival effect of Rut on neurons. Intracellular oxidative
      stress was significantly induced after H/R, which was inhibited by Rut and
      LY294002 as well as antioxidant PDTC. TRPV1 antagonist capsazepine or
      intracellular Ca2+ chelator BAPTA/AM could abolish these effects of Rut mentioned
      above. In summary, the present data suggest that Rut inhibits H/R-induced
      apoptosis of hippocampal neurons via TRPV1-[Ca2+]i-dependent and PI3K/Akt
      signaling pathway, which is related to inhibiting oxidative stress and caspase-3
      activation.

PMID- 18809422
TI  - Physiological stress response of young adults exposed to bullying during
      adolescence.
AB  - Peer victimization in the form of bullying is a chronic social stressor
      experienced by many humans during development. Exposure to bullying has been
      associated with a variety of mental disorders, such as anxiety and depression.
      Participants pre-selected for the presence or absence of a history of being
      bullied were brought into a laboratory and placed in a stressful situation. Blood
      pressure, heart rate, and salivary cortisol levels were measured before the
      introduction of the stressor (Time 1), at the end of the stressor (Time 2), and
      after its removal (Time 3). Men with a history of exposure to frequent bullying
      showed blunted blood pressure responses at Time 2 compared to control men.
      Bullied and Non-bullied women did not show any differences in any of the
      measures. Men and women in both groups showed an increase in heart rate in
      response to the stressor. There were no significant differences in salivary
      cortisol levels between Bullied and Non-bullied participants. However, salivary
      cortisol levels and systolic blood pressure were lower in Bullied male
      participants who reported having no feelings of anger about their experience
      compared to controls and those who did report anger. These data show altered
      sympathetic responses to stress in men with a history of victimization as well as
      suggesting long-term effects on the HPA axis in the most affected individuals.

PMID- 18809423
TI  - Attention to upside-down faces: An exception to the inversion effect.
AB  - When faces are turned upside-down, many aspects of face processing are severely
      disrupted. Here we report an instance where this face inversion effect is not
      found. In a visual cueing paradigm an inverted face was paired with an inverted
      object in a cue display, followed by a target in one of the cue locations
      (Experiment 1). Responses were faster to face-cued targets, indicating an
      attention bias for inverted faces. When upright and inverted face cues were
      paired in Experiment 2, no attention bias for either cue type was found,
      suggesting that attention was drawn equally to both types of stimuli. Despite
      this, attention could be biased selectively toward upright or inverted faces in
      Experiment 3, by manipulating the predictiveness of either type of cue, which
      shows that observers can distinguish upright and inverted faces under these
      conditions. A fourth experiment provided a replication of Experiment 2 with an
      extended stimulus set and increased task demands. These findings suggest that
      visual attributes that can influence the allocation of an observer's attention to
      faces are available in both upright and inverted orientations.

PMID- 18809424
TI  - Measurement of suprathreshold binocular interactions in amblyopia.
AB  - It has been established that in amblyopia, information from the amblyopic eye
      (AME) is not combined with that from the fellow fixing eye (FFE) under conditions
      of binocular viewing. However, recent evidence suggests that mechanisms that
      combine information between the eyes are intact in amblyopia. The lack of
      binocular function is most likely due to the imbalanced inputs from the two eyes
      under binocular conditions [Baker, D. H., Meese, T. S., Mansouri, B., & Hess, R.
      F. (2007b). Binocular summation of contrast remains intact in strabismic
      amblyopia. Investigative Ophthalmology & Visual Science, 48(11), 5332-5338]. We
      have measured the extent to which the information presented to each eye needs to
      differ for binocular combination to occur and in doing so we quantify the
      influence of interocular suppression. We quantify these suppressive effects for
      suprathreshold processing of global stimuli for both motion and spatial tasks.
      The results confirm the general importance of these suppressive effects in
      rendering the structurally binocular visual system of a strabismic amblyope,
      functionally monocular.

PMID- 18809425
TI  - Telomeres and frailty.
AB  - Associations between telomere length and various chronic diseases associated with
      ageing have led to the suggestion that telomere length may be an ageing
      biomarker. At the clinical level, the suggestion of using measurements of frailty
      as a measure of biological ageing has also been suggested. This study examines
      the hypothesis that telomere shortening may form the biological basis for
      frailty, using data obtained from a health survey of 2000 men and women aged 65
      years and over, living in the community, and followed up for 4 years to determine
      survival. Frailty was measured using the frailty index, a summation of deficits
      covering physical, psychological, and functional domains. Telomere length was
      measured in 976 men and 1030 women, using real-time quantitative polymerase chain
      reaction. Women were more frail than men but had longer telomere length. In men
      only, there was a negative association between telomere length and age and a
      positive association between frailty index and mortality after adjusting for age.
      There was no correlation between telomere length and frailty index in either sex.
      While telomere length may be a biomarker of cellular senescence, this
      relationship may not be extrapolated to the functional level represented by the
      frailty phenotype.

PMID- 18809426
TI  - Fear memory impairing effects of systemic treatment with the NMDA NR2B subunit
      antagonist, Ro 25-6981, in mice: attenuation with ageing.
AB  - N-methyl-D-aspartate receptors (NMDARs) are mediators of synaptic plasticity and
      learning and are implicated in the pathophysiology of neuropsychiatric disease
      and age-related cognitive dysfunction. NMDARs are heteromers, but the relative
      contribution of specific subunits to NMDAR-mediated learning is not fully
      understood. We characterized pre-conditioning systemic treatment of the NR2B
      subunit-selective antagonist Ro 25-6981 for effects on multi-trial, one-trial and
      low-shock Pavlovian fear conditioning in C57BL/6J mice. Ro 25-6981 was also
      profiled for effects on novel open field exploration, elevated plus-maze anxiety
      like behavior, startle reactivity, prepulse inhibition of startle, and
      nociception. Three-month (adult) and 12-month old C57BL/6Tac mice were compared
      for Ro 25-6981 effects on multi-trial fear conditioning, and corticolimbic NR2B
      protein levels. Ro 25-6981 moderately impaired fear learning in the multi-trial
      and one-trial (but not low-shock) conditioning paradigms, but did not affect
      exploratory or anxiety-related behaviors or sensory functions. Memory impairing
      effects of Ro 25-6981 were absent in 12-month old mice, although NR2B protein
      levels were not significantly altered. Present data provide further evidence of
      the memory impairing effects of selective blockade of NR2B-containing NMDARs, and
      show loss of these effects with ageing. This work could ultimately have
      implications for elucidating the pathophysiology of learning dysfunction in
      neuropsychiatric disorders and ageing.

PMID- 18809427
TI  - Diurnal variation in cue-induced responses among protracted abstinent heroin
      users.
AB  - OBJECTIVES: The physiological and psychological responses to drug cue exposure
      have been assessed in substance abusers. However, there is no study to
      demonstrate whether the responses to drug cue exposure are diurnal dependence.
      The present study was to examine whether there was a variation in drug-related
      cue reactivity across the diurnal cycle among recently abstinent opiate addicts.
      METHODS: Four groups of 20 abstinent heroin dependent patients (n=80) were
      exposed to both neutral and drug-related videos at four separate times during the
      day: 8:00, 12:00, 16:00, and 20:00 h. Physiological and psychological responses,
      including heart rate, blood pressure, heroin craving, and subjective anxiety were
      assessed before and after each cue exposure. RESULTS: Drug cue significantly
      increased craving ratings compared to neutral cues across all the four separate
      times of day. Drug cue-induced craving was greater in the morning (8:00 am) than
      noon (12:00 pm), but was similar to evening assessments (8 pm). Drug cues also
      significantly increased anxiety, which positively correlated with cue-induced
      craving. Drug cues increased heart rate, systolic and diastolic blood pressures,
      which were not correlated with cue-induced craving or anxiety. However, no time
      effects were found on the three physiological measures. CONCLUSIONS: Cue-induced
      craving could be profoundly affected by the time points of cue exposure, using
      cue-reactivity paradigm. The relative sensitivity of morning and evening
      assessments of drug craving suggests a need for replication and further research
      on mechanisms contributing to these diurnal variations.

PMID- 18809429
TI  - Monitoring the tobacco use epidemic I. Overview: Optimizing measurement to
      facilitate change.
AB  - OBJECTIVE: This Overview paper (I of V) summarizes research work to date on
      monitoring the tobacco use epidemic, discusses the recommendations made at the
      November, 2002 National Tobacco Monitoring, Research and Evaluation Workshop
      sponsored by the U.S. National Cancer Institute (NCI), Centers for Disease
      Control and Prevention (CDC), the American Legacy Foundation, and the Robert Wood
      Johnson Foundation on the topic of tobacco surveillance and evaluation, and
      discusses the current state of affairs. METHODS: A conceptual model based on the
      classical infectious diseases framework/paradigm focusing on the Agent, Host,
      Vector and Environment is used to integrate the work presented in the four other
      papers that appear in this supplemental issue of Preventive Medicine. RESULTS:
      The Agent paper (II) describes surveillance on tobacco products and biomarkers;
      the Host paper (III) describes surveillance on the smoker/user, or potential
      smoker/user; the Vector paper (IV) describes monitoring of industry activity; and
      the Environment paper (V) describes several key strategies for monitoring
      influential environmental factors. Overall, some improvements to the nation's
      surveillance system have been made in recent years. However, additional steps are
      needed to optimize measurement of tobacco use and factors influencing use in the
      United States. CONCLUSIONS: Tobacco monitoring efforts play a vital role in
      combating the epidemic of addiction and disease produced by various tobacco
      products. The knowledge and experience gained by the tobacco use prevention and
      control community through this commitment to linkages of data collected in the
      domains of Vector and Environment, in addition to Agent and Host, could inform
      monitoring of a wide range of other public health issues as well, including diet
      and nutrition, physical activity, overweight and obesity, and substance abuse.

PMID- 18809428
TI  - Increased impulsivity and disrupted attention induced by repeated phencyclidine
      are not attenuated by chronic quetiapine treatment.
AB  - Atypical antipsychotic medications differ in how effectively they attenuate
      cognitive and other deficits in schizophrenia. The present study aimed to explore
      whether quetiapine, an atypical antipsychotic medication, would reverse
      disruptions of performance in the 5-choice serial reaction time task (5-CSRTT), a
      test of attention and impulsivity, induced by repeated administration of the
      psychotomimetic phencyclidine (PCP). In confirmation of previous findings,
      repeated PCP administration (2 mg/kg, s.c., 30 min before behavioral testing, for
      2 consecutive days, followed by a 2-week PCP-free period and then 5 consecutive
      days of PCP treatment) increased premature responding (impulsivity), decreased
      accuracy (attention), and increased response latencies (processing speed) and
      timeout responding (impulsivity/cognitive inflexibility). Chronic quetiapine (5
      or 10 mg/kg/day, s.c.) did not attenuate these PCP-induced disruptions in
      performance, while at the highest dose used, quetiapine disrupted 5-CSRTT
      performance in the absence of PCP treatment and tended to exacerbate the PCP
      induced increase in premature responding. Considering that clozapine, another
      atypical antipsychotic, was shown previously to reverse PCP-induced deficits in
      the same task [Amitai N, Semenova S, Markou A. Cognitive-disruptive effects of
      the psychotomimetic phencyclidine and attenuation by atypical antipsychotic
      medications in rats. Psychopharmacology (Berl) 2007;193:521-37], the present
      findings demonstrate differences between clozapine and quetiapine in their
      effectiveness on schizophrenia-like cognitive deficits and impulsivity that may
      be attributable to their different receptor affinity profiles.

PMID- 18809430
TI  - Structural analysis of point mutations in the Hairless gene and their association
      with the activity of the Hairless protein.
AB  - The Notch signaling pathway (NSP) is an important intercellular communication
      mechanism that regulates embryo development and adult physiological functions.
      The Hairless (H) protein is a powerful antagonist of the NSP by its interaction
      with the Suppressor of Hairless (Su[H]) protein, recruiting the corepressors Gro
      and CtBP. In the present work, we examined the role of several important amino
      acids in different H protein domains analyzing four mutant lines of Drosophila
      melanogaster. The mutant alleles were evaluated by single-strand conformational
      polymorphism (SSCP) analysis and we located mutated regions at different
      positions along the sequence of the Hairless gene.

PMID- 18809431
TI  - Chitosan/polyethylene glycol diacrylate films as potential wound dressing
      material.
AB  - Michael addition reaction of Chitosan (CS) and polyethylene glycol diacrylate
      (PEGDA) was carried out successfully in acidic solution. Films with CS/PEGDA
      weight ratios from 100/0 to 0/100 in 10% increments were analyzed by Fourier
      transform infrared (FTIR) spectroscopy, Scanning Electron Microscope (SEM) and X
      Ray Diffraction (XRD). Additionally, the films were characterized by measuring
      mechanical property, swelling property. The potential application of the CS/PEGDA
      film as wound dressing material was evaluated in vitro by using mouse fibroblasts
      (L929) as reference cell lines, indirect cytotoxicity assessment indicated that
      CS/PEGDA films were nontoxic to L929 cell.

PMID- 18809432
TI  - The function of rhamnose-binding lectin in innate immunity by restricted binding
      to Gb3.
AB  - L-rhamnose-binding lectins (RBLs) have been isolated from various kinds of fish
      and invertebrates and interact with various kinds of bacteria, suggesting RBLs
      are involved in various inflammatory reactions. We investigated the effect of
      RBLs from chum salmon (Oncorhynchus keta), named CSL1, 2 and 3, on the peritoneal
      macrophage cell line from rainbow trout (Oncorhynchus mykiss) (RTM5) and an
      established fibroblastic-like cell line derived from gonadal tissue of rainbow
      trout (RTG-2). CSLs were bound to the surface of RTM5 and RTG-2 cells and induced
      proinflammatory cytokines, including IL-1beta1, IL-1beta2, TNF-alpha1, TNF-alpha2
      and IL-8 in both cells by recognizing globotriaosylceramide (Gb3). In addition,
      CSLs had an opsonic effect on RTM5 cells and this effect was significantly
      inhibited by L-rhamnose, indicating that CSLs enhanced their phagocytosis by
      binding to Gb3 on cell surfaces. This is the first finding that Gb3 plays a role
      in innate immunity by cooperating with natural ligands, RBLs.

PMID- 18809433
TI  - 1-Phenoxy-2-propanol is a useful anaesthetic for gastropods used in
      neurophysiology.
AB  - Anaesthesia is often used in neurophysiological, surgical, and neuroanatomical
      protocols. Several anaesthetics, including magnesium chloride, volatiles
      (halothane, etc.), and barbiturates, have been used in gastropod neurobiology. 1
      Phenoxy-2-propanol (PP) is another anaesthetic option that has not yet been used
      extensively. We provide an analysis of the neural, muscular and behavioural
      effects of PP in gastropods. PP eliminates action potentials and reduces muscular
      contraction force in Hermissenda crassicornis, and eliminates behavioural
      activity in Tritonia diomedea. Our results show these effects are reversible,
      with complete action potential recovery, at least partial muscular recovery, and
      full behavioural recovery. Survival after surgery in T. diomedea was longer with
      PP than without anaesthetic, and PP also reduced contraction during tissue
      fixation in Lymnaea stagnalis. Moreover, PP can be bath applied, has low
      toxicity, and is biodegradable. Thus, PP is an effective anaesthetic in three
      species of gastropods, and useful in neurophysiological dissection, surgical, and
      fixation protocols.

PMID- 18809434
TI  - Striatal volume differences between non-human and human primates.
AB  - Convection-enhanced delivery (CED) has recently entered the clinic and represents
      a promising new delivery option for targeted gene therapy in Parkinson's disease
      (PD). The prime stereotactic target for the majority of recent gene therapy
      clinical trials has been the human putamen. The stereotactic delivery of
      therapeutic agents into putamen (or other subcortical structures) via CED remains
      problematic due to the difficulty in knowing what volume of therapeutic agent to
      deliver. Preclinical studies in non-human primates (NHP) offer a way to model
      treatment strategies prior to clinical trials. Understanding more accurately the
      volumetric differences in striatum, especially putamen, between NHP and humans is
      essential in predicting convective volume parameters in human clinical trials. In
      this study, magnetic resonance images (MRI) were obtained for volumetric
      measurements of striatum (putamen and caudate nucleus) and whole brain from 11 PD
      patients, 13 aged healthy human subjects, as well as 8 parkinsonian and 30 normal
      NHP. The human brain is 13-18 times larger than the monkey brain. However, this
      ratio is significantly smaller for striatum (5.7-6.5), caudate nucleus (4.6-6.6)
      and putamen (4.4-6.6). Size and species of the monkeys used for this comparative
      study are responsible for differences in ratios for each structure between
      monkeys and humans. This volumetric ratio may have important implications in the
      design of clinical therapies for PD and Huntington's disease and should be
      considered when local therapies such as gene transfer, local protein
      administration or cellular replacement are translated based on NHP research.

PMID- 18809435
TI  - Essential roles of SHPS-1 in induction of contact hypersensitivity of skin.
AB  - SHPS-1 is a transmembrane protein that binds the protein tyrosine phosphatases
      SHP-1 and SHP-2 and is abundant on the surface of CD11c(+) dendritic cells (DCs).
      We recently showed that SHPS-1 is essential for priming by DCs of CD4(+) T cells
      and for development of Th17 cell-mediated experimental autoimmunity. We have now
      further evaluated the importance of SHPS-1 and that of its ligand CD47 in contact
      hypersensitivity (CHS) to 2,4-dinitro-1-fluorobenzene (DNFB). Whereas the DNFB
      induced CHS response was impaired in mice that express a mutant form of SHPS-1
      lacking most of the cytoplasmic region, it was unaffected in CD47-deficient mice.
      Moreover, treatment of wild-type mice with mAbs to SHPS-1 that either block or do
      not block the binding of SHPS-1 to CD47 inhibited the CHS response. A mAb to CD47
      had no such effect. The 2,4-dinitro-benzenesulfonic acid-induced proliferation
      of, and production of IFN-gamma or IL-17 by, T cells from DNFB-sensitized wild
      type mice were inhibited by either mAb to SHPS-1 but not by that to CD47. In
      contrast, the blocking mAbs to SHPS-1, but not that to CD47, inhibited an
      allogeneic mixed leukocyte reaction. Both mAbs to SHPS-1, but not that to CD47,
      also inhibited the lipopolysaccharide- or polyinosinic-polycytidylic acid-induced
      production of TNF-alpha by DCs. These results suggest that SHPS-1 is essential
      for development of CHS, likely as a result of its positive regulation of the
      priming by DCs of CD4(+) T cells. However, such regulation by SHPS-1 does not
      appear to require its interaction with CD47.

PMID- 18809436
TI  - A scintillation proximity assay for dengue virus NS5 2'-O-methyltransferase
      kinetic and inhibition analyses.
AB  - Dengue virus (DENV) NS5 possesses methyltransferase (MTase) activity at its N
      terminal amino acid sequence and is responsible for formation of a type 1 cap
      structure, m(7)GpppAm(2'-O) in the viral genomic RNA. Optimal in vitro conditions
      for DENV2 2'-O-MTase activity were characterized using purified recombinant
      protein and a short biotinylated GTP-capped RNA template. Steady-state kinetics
      parameters derived from initial velocities were used to establish a robust
      scintillation proximity assay for compound testing. Pre-incubation studies showed
      that MTase-AdoMet and MTase-RNA complexes were equally catalytically competent
      and the enzyme supports a random bi bi kinetic mechanism. The assay was validated
      with competitive inhibitory agents, S-adenosyl-homocysteine and two homologues,
      sinefungin and dehydrosinefungin. A GTP-binding pocket present at the N-terminal
      of DENV2 MTase was previously postulated to be the cap-binding site.
      Interestingly, inhibition of the enzyme by GTP was two-fold lower than with RNA
      cap analogues, G[5']ppp[5']A and m(7)G[5']ppp[5']A and about three-fold poorer
      than a two-way methylated analogue, m(7)G[5']ppp[5']m(7)G. This assay allows
      rapid and highly sensitive detection of 2'-O-MTase activity and can be readily
      adapted for high-throughput screening for inhibitory compounds. It is suitable
      for determination of enzymatic activities of a wide variety of RNA capping
      MTases.

PMID- 18809437
TI  - Repeated intravenous amphetamine exposure: rapid and persistent sensitization of
      50-kHz ultrasonic trill calls in rats.
AB  - Short 50-kilohertz (kHz) range frequency-modulated ultrasonic vocalizations
      (USVs) produced by rats and mice are unconditionally elicited by drugs of abuse
      or electrical stimulation that increase dopamine activity in the nucleus
      accumbens, and it has been suggested that they reflect "positive affect" or
      incentive motivational states associated with appetitive behavior. The repeated
      administration of amphetamine is known to not only produce "psychomotor"
      sensitization, but also to facilitate a number of appetitive behaviors, including
      conditioned drug pursuit behavior. We were interested, therefore, in whether
      amphetamine-induced 50-kHz USVs would also increase with repeated drug exposure.
      USV recordings were made during 5-min sessions immediately after a saline
      infusion, and again 4-5h later after 1.0mg/kg intravenous amphetamine exposure.
      These sessions took place every other day over a 5-day period. A challenge dose
      of 1.0mg/kg amphetamine was administered 2 weeks later to determine whether
      sensitization would persist. The initial amphetamine infusion increased 50-kHz
      USVs relative to the saline infusion. This effect was enhanced over trials and
      during the amphetamine challenge 2 weeks later. Classification of 50-kHz range
      call types revealed that complex frequency-modulated trill calls were sensitized
      by amphetamine, but not flat 50-kHz calls. It is possible that 50-kHz USV
      recordings could provide a potentially valuable behavioral measure of
      sensitization linked to enhanced incentive salience and increased tendency to
      self-administer drugs of abuse.

PMID- 18809438
TI  - Ginsenosides attenuate kainic acid-induced synaptosomal oxidative stress via
      stimulation of adenosine A(2A) receptors in rat hippocampus.
AB  - Treatment with ginsenosides attenuated KA-induced seizures and oxidative stress
      in the synaptosome, and reduced synaptic vesicles at the presynaptic terminals
      dose-dependently. The adenosine A(2A) receptor antagonist 1,3,7-trimethyl-8-(3
      chlorostyryl) xanthine reversed the ginsenoside-mediated pharmacological actions.
      Neither the adenosine A(1) receptor antagonist 8-cyclopentyl-1,3-dimethylxanthine
      nor the adenosine A(2B) receptor antagonist alloxazine affected the ginsenoside
      mediated pharmacological actions. Our results suggest that ginsenosides block KA
      induced synaptosomal oxidative stress, associated with hippocampal degeneration,
      through activation of adenosine A(2A) receptors.

PMID- 18809439
TI  - Effects of foraging demand on maternal behaviour and adult offspring anxiety and
      stress response in C57BL/6 mice.
AB  - It has been proposed that developmental plasticity of anxiety and stress
      responses in rodents is mediated by environment-dependent variations in maternal
      behaviour, but recent evidence indicates that other factors must be involved. To
      examine this further, we exposed lactating C57BL/6 mice to environmental
      conditions that imposed high- (HFD), low- (LFD) or variable-foraging demand (VFD)
      from postnatal day 1-13, depending on the amount and predictability of food
      supply. While nest attendance was unaffected by treatment, both HFD and VFD-dams
      showed increased active maternal care compared to LFD-dams. Anxiety in adult male
      and female offspring was examined on an elevated-O-maze (EZM) and in the open
      field test, while hypothalamo-pituitary-adrenal (HPA) reactivity to 20min
      novelty/isolation stress was determined based on changes in plasma corticosterone
      (CORT) levels. There were no persistent treatment effects on the offspring's CORT
      response to novelty/isolation stress. However VFD-males, but not HFD-males,
      behaved more anxious than LFD males. Their reduced activities throughout the
      behavioural tests are indicative of a more passive coping style. Conversely, VFD
      females, but not HFD-females, behaved less anxious than LFD-females. Our results
      demonstrate (1) that maternal behaviour in C57BL/6 mice is sensitive to specific
      characteristics of the environment, (2) that even subtle environment-dependent
      variations in maternal behaviour can have persistent effects on the offspring's
      behavioural phenotype, (3) that other factors besides active maternal care must
      have contributed to these effects, and (4) that male and female offspring may be
      differentially sensitive to early maternal and/or environmental cues.

PMID- 18809440
TI  - ERK and p38 pathways regulate amino acid signalling.
AB  - The ribosomal protein S6 kinase 1 (S6K1) is emerging as a common downstream
      target of signalling by hormones and nutrients such as insulin and amino acids.
      Here, we have investigated how amino acids signal through the S6K1 pathway.
      First, we found that a commercial anti-phospho-Thr389-S6K1 antibody detects an 80
      90 kDa protein that is rapidly phosphorylated in response to amino acids.
      Unexpectedly, this phosphorylation was insensitive to both mTOR and PI-3 kinase
      inhibitors, and knockdown experiments showed that this protein was not S6K1.
      Looking for candidate targets of this phosphorylation, we found that amino acids
      stimulated phosphorylation of RSK and MSK kinases at residues that are homologous
      to Thr389 in S6K1. In turn, these phosphorylations required the activity of
      either p38 or ERK MAP kinases, which could compensate for each other. Moreover,
      we show that these MAP kinases are also needed for the amino acid-induced
      phosphorylation of S6K1 at Thr421/Ser424, as well as for that of S6K1 substrate,
      the S6 ribosomal protein. Consistent with these results, concomitant inhibition
      of p38 and ERK pathways also antagonised the well-known effects of amino acids on
      the process of autophagy. Altogether, these findings demonstrate a previously
      unknown role for MAP kinases in amino acid signalling.

PMID- 18809441
TI  - EEG photic driving: right-hemisphere reactivity deficit in childhood autism. A
      pilot study.
AB  - In 14 autistic boys, aged 6-14 years, free of drug treatment, with relatively
      intact verbal functions and without severe or moderate mental retardation (I.Q.
      91.4+/-22.8), intermittent photic stimulation at 11 fixed frequencies of 3-24 Hz
      revealed latent deficiency of the right hemisphere in the photic driving
      reactivity, predominantly at the fast alpha and beta frequencies of stimulation.
      The left-side prevalence was observed: 1) in the total number of driving peaks
      evaluated for the first four harmonics in the EEG spectra of 14 cortical areas
      and 2) in the driving amplitude in the spectra of the 2 occipital areas. As
      compared to 21 normally developing boys matched on age who did not show
      interhemispheric asymmetry in the driving reactivity, the autistic patients had
      significantly lower driving characteristics only in the right hemisphere. There
      were no significant differences between the autistic and control groups in the
      spontaneous EEG spectra of the occipital areas in the resting state.

PMID- 18809442
TI  - Early ERP components differentially extract facial features: evidence for spatial
      frequency-and-contrast detectors.
AB  - It is generally accepted that the N170 component of an event-related potential
      (ERP) reflects the structural encoding of faces and is specialized for face
      processing. Recent neuroimaging and ERP studies have demonstrated that spatial
      frequency is a crucial factor for face recognition. To clarify which early ERP
      components reflect either coarse (low spatial frequency, LSF) or fine (high
      spatial frequency, HSF) processing of faces, we recorded ERPs induced by
      manipulated face stimuli. By filtering the original grayscale faces (broadband
      spatial frequency) spatially, we created LSF and HSF face stimuli. Next, we
      created physically equiluminant (PEL) face stimuli to eliminate the effects of
      lower order information, such as luminance and contrast. The P1 amplitude at the
      occipital region was augmented by LSF faces, while the N170 amplitude increased
      for HSF faces. The occipital P1 amplitude for PEL faces was relatively unaffected
      compared with that for PEL houses. In addition, the occipital N2 for PEL faces
      was spatiotemporally separable from N170 in a time-window between P1 and N170.
      These results indicate that P1 reflects coarse processing of faces, and that the
      face robustness further assures face-specific processing in the early component.
      Moreover, N2 reflects the early contrast processing of faces whereas N170
      analyzes the fine facial features. Our findings suggest the presence of spatial
      frequency-and-contrast detectors for face processing.

PMID- 18809443
TI  - Complex dynamics of microbial competition in the gradostat.
AB  - We examine the conditions necessary for the emergence of complex dynamic behavior
      in systems of microbial competition. In particular, we study the effect of
      spatial heterogeneity and substrate-inhibition on the dynamics of such a system.
      This is accomplished through the study of a mathematical model of two microbial
      populations competing for a single nutrient in a configuration of two
      interconnected chemostats. Microbial growth is assumed to follow substrate
      inhibited kinetics for both species. Such a system with sterile feed has been
      shown in a previous work to exhibit stable periodic states. In the present work
      we study the system for the case of non-sterile feed, i.e., when the two species
      are present in the feed of the chemostats. The analysis is done by numerical
      bifurcation theory methods. We demonstrate that, in addition to periodic states,
      the system possesses stable quasi-periodic states resulting from Neimark-Sacker
      bifurcations of limit cycles. Also, periodic states may undergo successive period
      doublings leading to periodic states of increasing period and indicating that
      chaotic states might be possible. Multistability is also observed, consisting in
      the coexistence of several stable steady states and possibly stable periodic or
      quasi-periodic states for given operating conditions. It appears that substrate
      inhibition, spatial heterogeneity and presence of microorganisms in the inflow
      are all necessary conditions for complex dynamics to arise in a microbial system
      of pure and simple competition.

PMID- 18809444
TI  - Heat shock effect upon dengue virus replication into U937 cells.
AB  - The molecules involved in dengue virus entry into human cells are currently
      unknown. We have previously shown that two surface heat shock proteins (Hsps),
      Hsp90 and Hsp70 are part of a receptor complex in monocytic cells. In the present
      report, the effect of heat shock (HS) on dengue virus infection is analyzed. We
      have documented a more than twofold increase in dengue virus infectivity after HS
      treatment in monocytic cells U937; this effect correlates mainly with an increase
      in viral entry due to a major presence of both Hsps on the surface of monocytic
      cells, particularly in membrane microdomains. Interestingly, since heat shock
      treatment at 6h post-infection also increased viral yields, it is likely that HS
      also modulates positively dengue virus replication.

PMID- 18809445
TI  - Characterization of a Bombyx mori nucleopolyhedrovirus with Bmvp80 disruption.
AB  - A BmNPV Bacmid with the Bmvp80 gene disrupted was constructed using the ET
      recombination system in Escherichia coli to investigate the role of Bmvp80 during
      the baculovirus life cycle. Disruption of Bmvp80 resulted in single cell
      infection phenotype, whereas a rescue BmBacmid restored budded virus titers to
      wild type levels; however, the homologous gene Ac104 (Acvp80) from AcMNPV could
      not complement the BmBacmid lacking a functional Bmvp80 gene. Electron microscopy
      of cells transfected with BmNPV lacking functional Bmvp80 revealed that the
      number of nucleocapsids was markedly lower. These results suggest that Bmvp80 is
      essential for normal budded virus production and nucleocapsid maturation, and is
      functionally divergent between baculovirus species.

PMID- 18809446
TI  - The safety of post-exposure vaccination of mice infected with Mycobacterium
      tuberculosis.
AB  - New post-exposure tuberculosis vaccination strategies are being developed to
      prevent disease in individuals latently infected with Mycobacterium tuberculosis.
      However, concerns about the potential induction of deleterious Koch-like
      reactions after immunization of persons with latent tuberculosis has limited
      progress in assessing the effectiveness of post-exposure vaccination. To evaluate
      the safety of immunization after M. tuberculosis infection, two mouse models were
      established, a drug treatment low bacterial burden model and an active disease
      model. Twelve different M. tuberculosis antigen preparations and vaccines
      (including DNA, subunit, viral vectored, and live, attenuated vaccines) were
      evaluated using these mouse models. In the low bacterial burden model, post
      exposure vaccination did not induce significant reactivational disease and only
      injection of BCG evoked increases in lung inflammatory responses at 1 month after
      the immunizations. Additionally, although significant increases in lung
      inflammation were seen for animals injected with the hps65 DNA vaccine or a M.
      tuberculosis culture supernatant preparation, no differences in the survival
      periods were detected between vaccinated and non-vaccinated mice at 10 months
      post-immunization using the low bacterial burden model. For the active disease
      model, significantly more lung inflammation was observed at 1 month after
      administration of the hsp65 DNA vaccine but none of the antigen preparations
      tested increased the lung bacterial burdens at this early time point.
      Furthermore, vaccination of diseased mice with BCG or TB DNA vaccines did not
      significantly affect mortality rates compared to non-vaccinated controls at 10
      months post-immunization. Overall, these data suggest that while the potential
      risk of inducing Koch-like reactions is low after immunization of persons with
      latent tuberculosis, extreme caution is still needed as post-exposure vaccines
      progress from pre-clinical experiments into the initial phases of clinical
      testing.

PMID- 18809447
TI  - Comparison of multiple vaccine vectors in a single heterologous prime-boost
      trial.
AB  - The prevention of infectious disease via prophylactic immunization is a mainstay
      of global public health efforts. Vaccine design would be facilitated by a better
      understanding of the type and durability of immune responses generated by
      different vaccine vectors. We report here the results of a comparative
      immunogenicity trial of six different vaccine vectors expressing the same insert
      antigen, cowpox virus B5 (CPXV-B5). Of those vectors tested, recombinant
      adenovirus (rAd5) was the most immunogenic, inducing the highest titer anti-B5
      antibodies and conferring protection from sublethal vaccinia virus challenge in
      mice after a single immunization. We tested select heterologous prime-boost
      combinations and identified recombinant vesicular stomatitis virus (rVSV) and
      recombinant Venezuelan equine encephalitis virus replicons (VRP) as the most
      synergistic regimen. Comparative data such as those presented here are critical
      to efforts to generate protective vaccines for emerging infectious diseases as
      well as for biothreat agents.

PMID- 18809448
TI  - Baculovirus surface display of sigmaC and sigmaB proteins of avian reovirus and
      immunogenicity of the displayed proteins in a mouse model.
AB  - Avian reovirus (ARV), an important pathogen in poultry, causes arthritis, chronic
      respiratory disease, and malabsorption syndrome that cause considerable economic
      losses to the poultry industry. In present study, we have succeeded in
      construction of a universal baculovirus surface display system (UBSDS) that can
      display different foreign proteins on the envelope of baculovirus. Sequences
      encoding the signal peptide (SS), transmembrane domain (TM), and cytoplasmic
      domain (CTD) derived from the gp64 protein of baculovirus and histidine tag,
      respectively were inserted into the pBacCE vector. Four restriction enzyme sites
      between the histidine tag and gp64 transmembrane domain were established for
      expression of different foreign proteins. The transmembrane domain and CTD of
      gp64 in the platform were designed in order to improve stability and quantity of
      foreign proteins on the envelope of baculovirus. The sigmaC and sigmaB proteins
      of ARV are known to elicit neutralizing antibodies against ARV. The UBSDS was
      therefore used to express sigmaC and sigmaB proteins on the envelope of
      baculovirus. Two recombinant baculoviruses BacSC-sigmaC and BacSC-sigmaB have
      been successfully constructed. After infection, both His6-tagged recombinant
      sigmaC (rsigmaC) and sigmaB (rsigmaB) proteins were displayed on the envelope of
      recombinant baculoviruses and the recombinant viral proteins were anchored on the
      plasma membrane of Sf-9 cells, as revealed by immunofluorescence staining (IFS)
      and confocal microscopy. The antigenicity of rsigmaC and rsigmaB proteins was
      demonstrated by Western blotting assay. Immunogold electron microscopy
      demonstrated that both recombinant viruses displayed rsigmaC and rsigmaB proteins
      on the viral surface. Immunization of BALB/c mice with recombinant viruses,
      demonstrated that serum from the BacSC-sigmaC and BacSC-sigmaB treated models had
      significant higher levels of virus neutralization activities than the control
      groups. This demonstrates that the recombinant baculoviruses BacSC-sigmaC and
      BacSC-sigmaB can be a potential vaccine against ARV infections.

PMID- 18809449
TI  - Adverse event reports following yellow fever vaccination.
AB  - Yellow fever (YF) vaccine has been used for prevention of YF since 1937 with over
      500 million doses administered. However, rare reports of severe adverse events
      following vaccination have raised concerns about the vaccine's safety. We
      reviewed reports of adverse events following YF vaccination reported to the U.S.
      Vaccine Adverse Event Reporting System (VAERS) from 2000 to 2006. We used
      estimates of age and sex distribution of administered doses obtained from a 2006
      survey of authorized vaccine providers to calculate age- and sex-specific
      reporting rates of all serious adverse events (SAE), anaphylaxis, YF vaccine
      associated neurotropic disease, and YF vaccine-associated viscerotropic disease.
      Reporting rates of SAEs were substantially higher in males and in persons aged >
      or =60 years. These findings reinforce the generally acceptable safety profile of
      YF vaccine, but highlight the importance of physician and traveler education
      regarding the risks and benefits of YF vaccination, particularly for travelers >
      or =60 years of age. Vaccination should be limited to persons traveling to areas
      where the risk of YF is expected to exceed the risk of serious adverse events
      after vaccination, or if not medically contraindicated, where national
      regulations require proof of vaccination to prevent introduction of YF.

PMID- 18809450
TI  - Cytoplasmic delivery of antigens, by Bacillus subtilis enhances Th1 responses.
AB  - Endospores of the Gram-positive bacterium, Bacillus subtilis, have been used
      successfully for delivery of antigens where the immunogen is expressed on the
      spore surface. In this work the spore has been engineered to deliver antigens to
      the cytoplasm of macrophages by expressing listeriolysin O (LLO) or a derivative,
      LLO(L461T), that is stable at neutral pH, from the B. subtilis vegetative cell.
      Following phagocytosis spores were shown to germinate in the phagosome enabling
      secretion of LLO/LLO(L461T) and entry of the bacterium into the cytosol. We have
      shown that in the cytosol B. subtilis proliferates before eventually being
      destroyed. Immunisation of mice with spores that co-expressed LLO with Protective
      Antigen (PA) of Bacillus anthracis generated an increase in IgG2a against PA,
      toxin-neutralising activity coupled with specific IFN-gamma and IL-12 (and
      reduced IL-4) responses of splenocytes, both indicative of an enhanced Th1
      response. Enhanced Th1 responses via LLO co-expression of antigen by B. subtilis
      spores may be a useful strategy to improve vaccine performance.

PMID- 18809451
TI  - Derivation of a chronic reference dose and reference concentration for
      trimethylbenzenes and C9 aromatic hydrocarbon solvents.
AB  - Trimethylbenzenes (TMBs) and C9 aromatic hydrocarbon solvents are structurally
      similar and have similar toxicity. Based on a review of the entire TMB and C9
      aromatic hydrocarbon solvents toxicology database, oral and inhalation studies
      were identified to serve as the basis for a Reference dose (RfD) and Reference
      concentrations (RfC). The RfD and RfC were derived using standard USEPA methods
      and assumptions. The RfD was calculated to be 0.4 mg/kg/day using a 90-day oral
      study that resulted in a NOAEL of 600 mg/kg/day, based on a lack of adverse
      effects at the highest dose level (reversible effects such as increased serum
      phosphorus levels and liver and kidney weights), along with a total uncertainty
      factor of 1000. For the RfC, three studies were considered based on different
      study designs and toxicological endpoints, including neurotoxicity, systemic
      toxicity, and potential developmental and reproductive toxicity. For all three
      studies, as the calculated RfCs were consistent (3-4 mg/m3), the most
      conservative RfC, 3mg/m3, was selected. The C9 aromatic hydrocarbon solvents
      referred to herein are based on chemistries assessed as part of the TSCA Section
      4 Test Rule. These solvents contain primarily ethyl toluene and tri-methyl
      benzene isomers, but the specific compositions can vary based on feedstock and
      manufacturing process, thus, it is important to consider the composition of any
      specific solvent to assess similarity to that assessed in the TSCA Section 4 Test
      Rule program.

PMID- 18809452
TI  - Evaluation of asbestos exposure within the automotive repair industry: a study
      involving removal of asbestos-containing body sealants and drive clutch
      replacement.
AB  - Two independent assessments were performed of airborne asbestos concentrations
      generated during automotive repair work on vintage vehicles . The first involved
      removal of asbestos-containing seam sealant, and the second involved servicing of
      a drive clutch. Despite the relatively high concentrations (5.6-28%) of
      chrysotile fibers detected within bulk samples of seam sealant, the average
      asbestos concentration for personal breathing zone (PBZ) samples during seam
      sealant removal was 0.006 f/cc (fibers/cubic centimeter of air). Many other air
      samples contained asbestos at or below the analytical limit of detection (LOD).
      Pneumatic chiseling of the sealant material during removal resulted in 69% of
      area air samples containing asbestos. Use of this impact tool liberated more
      asbestos than hand scraping. Asbestos fibers were only detected in air samples
      collected during the installation of a replacement clutch. The highest asbestos
      corrected airborne fiber concentration observed during clutch installation was
      0.0028 f/cc. This value is approximately 100 times lower than Occupational Safety
      and Health Administration's (OSHA) permissible exposure limit (PEL) of 0.1f/cc.
      The airborne asbestos concentrations observed during the servicing of vintage
      vehicles with asbestos-containing seam sealant and clutches are comparable to
      levels reported for repair work involving brake components and gaskets.

PMID- 18809453
TI  - Quetiapine-induced rabbit syndrome in a patient with bipolar disorder.

PMID- 18809454
TI  - Comparative evaluation of the hypolipidemic effects of coconut water and
      lovastatin in rats fed fat-cholesterol enriched diet.
AB  - The coconut water presents a series of nutritional and therapeutic properties,
      being a natural, acid and sterile solution, which contains several biologically
      active components, l-arginine, ascorbic acid, minerals such as calcium, magnesium
      and potassium, which have beneficial effects on lipid levels. Recent studies in
      our laboratory showed that both tender and mature coconut water feeding
      significantly (P<0.05) reduced hyperlipidemia in cholesterol fed rats [Sandhya,
      V.G., Rajamohan, T., 2006. Beneficial effects of coconut water feeding on lipid
      metabolism in cholesterol fed rats. J. Med. Food 9, 400-407]. The current study
      evaluated the hypolipidemic effect of coconut water (4ml/100g body weight) with a
      lipid lowering drug, lovastatin (0.1/100g diet) in rats fed fat-cholesterol
      enriched diet ad libitum for 45 days. Coconut water or lovastatin supplementation
      lowered the levels of serum total cholesterol, VLDL+LDL cholesterol,
      triglycerides and increased HDL cholesterol in experimental rats (P<0.05).
      Coconut water feeding decreased activities of hepatic lipogenic enzymes and
      increased HMG CoA reductase and lipoprotein lipase activity (P<0.05).
      Incorporation of radioactive acetate into free and ester cholesterol in the liver
      were higher in coconut water treated rats. Coconut water supplementation
      increased hepatic bile acid and fecal bile acids and neutral sterols (P<0.05).
      Coconut water has lipid lowering effect similar to the drug lovastatin in rats
      fed fat-cholesterol enriched diet.

PMID- 18809455
TI  - Sodium arsenite induced biochemical perturbations in rats: ameliorating effect of
      curcumin.
AB  - The present study was undertaken to evaluate the therapeutic efficacy of curcumin
      in terms of normalization of altered biochemical parameters following sodium
      arsenite treatment in rats. Animals were divided into four groups. The first
      group was used as control. While, groups 2, 3 and 4 were orally treated with
      curcumin (Cur, 15 mg/kg BW), sodium arsenite (Sa, 5 mg/kg BW) and sodium arsenite
      plus curcumin, respectively. Results showed that the activities of transaminases
      and phosphatases were significantly decreased in liver due to Sa administration,
      whereas increased in plasma. The activity of brain and plasma
      acetylcholinesterase (AChE) was decreased in rats treated with Sa. Also, Sa
      significantly decreased plasma total protein (TP), albumin (Alb) and high density
      lipoprotein-cholesterol (HDL-c), while increased glucose, urea, creatinine,
      bilirubin, total lipid (TL), cholesterol, triglyceride (TG) and low density
      lipoprotein-cholesterol (LDL-c). Curcumin alone decreased the levels of glucose,
      urea, creatinine, TL, cholesterol, TG and LDL-c. Curcumin reduced Sa-induced
      transaminases, phosphatases, glucose, urea, creatinine, bilirubin, TL,
      cholesterol and TG. Moreover, curcumin induced Sa-reduced liver transaminases and
      phosphatases, plasma and brain AChE, and the levels of TP and Alb. Experimental
      results, therefore suggested that curcumin protects arsenic induced biochemical
      alterations in rats.

PMID- 18809456
TI  - Effect of a glycoprotein from Hizikia fusiformis on acetaminophen-induced liver
      injury.
AB  - In this study, we isolated a glycoprotein from the brown alga Hizikia fusiformis
      (HFGP) and examined whether it could protect against Acetaminophen (AAP)-induced
      liver injury in vivo and in vitro. AAP, one of the most commonly abused drugs,
      may cause fatal liver injury. An analysis of the effects of HFGP on AAP toxicity
      in rats revealed that the serum glutamic pyruvic transaminase level was restored
      to the control level and glutathione level was also increased by co-treatment
      with HFGP and AAP. Furthermore, HFGP co-treatment decreased caspase-3/-9
      activity. These results indicate that HFGP may inhibit AAP-induced liver injury
      in Sprague-Dawley rats. Several lines of evidence indicate that oxidative stress
      plays an important role in AAP-induced liver injury and mitogen-activated protein
      kinase (MAPK) signaling is involved in the regulation of oxidative stress.
      Therefore, Western blotting was used to determine which MAPK signaling pathway is
      involved in the protective effect of HFGP against AAP toxicity in HepG2 cells. We
      found that ERK activation was involved in the protective effect of HFGP against
      AAP-induced cell death. Therefore, we propose that MAPK signaling is involved in
      the protective effect of HFGP against AAP-induced liver injury.

PMID- 18809457
TI  - Effects of dietary selenium supplementation on serum and liver selenium, serum
      malondialdehyde and liver glutathione peroxidase activity in rats consuming
      thermally oxidized sunflower oil.
AB  - The present study compared the effects of four isocaloric diets containing (1)
      fresh sunflower oil not supplemented with selenium (Fresh), (2) oxidized
      sunflower oil not supplemented with selenium (Oxidized), (3) fresh sunflower oil
      supplemented with 1 ppm selenium as sodium selenite (Fresh+Se), (4) oxidized
      sunflower oil supplemented with 1 ppm selenium as sodium selenite (Oxidized+Se)
      on serum MDA concentrations, liver GPx activity and serum and liver selenium
      contents in growing male Sprague Dawley rats during a period of 43 days. The
      oxidized oil used was prepared by heating fresh sunflower oil at 180 degrees C
      for 48 h. Serum and liver selenium contents and liver GPx activity were
      significantly higher in the selenium supplemented groups compared to the non
      selenium supplemented groups, but these parameters did not differ significantly
      between the oxidized oil fed groups and the fresh oil fed groups. Serum MDA
      concentrations increased significantly in the Oxidized group compared to the
      Fresh group. This suggests that the ingestion of oxidized oil resulted in, in
      vivo lipid peroxidation. Serum MDA concentrations remained significantly higher
      even in comparison of the Oxidized + Se group with the Oxidized group. Our
      results emphasize that the consumption of oxidized oil increases in vivo lipid
      peroxidation and thus can be deleterious to health. However, we did not observe a
      significant beneficial effect of selenium supplementation upon the ingestion of
      thermally oxidized oil on lipid peroxidation.

PMID- 18809458
TI  - A quantitative inverse relationship between connexin32 expression and cell
      proliferation in a rat hepatoma cell line.
AB  - Gap junctions comprised of connexin proteins are involved in direct intercellular
      communication and the regulation of cell behaviour and homeostasis. Reduced
      connexin expression and loss of gap junction function is a characteristic of many
      cancer cells and of the effect of many non-genotoxic carcinogens that induce cell
      proliferation. Moreover, when certain cancer cell lines are transfected with
      specific connexin genes, cells can regain control over proliferation. We have
      employed RNA interference and dexamethasone to modulate connexin32 expression in
      MH(1)C(1) cells to a range of concentrations. This allowed the determination of
      the quantitative relationship between connexin32 protein expression and cell
      proliferation. The magnitude of cell proliferation, measured by bromodeoxyuridine
      incorporation, was inversely proportional to the level of connexin32 expression.
      Q-PCR indicated a lack of change of expression of a range of cell cycle-related
      genes at 24h. The inverse relationship between Cx32 expression and proliferation
      was continuous, and a threshold level of reduction of connexin32 was not
      observable for an influence on proliferation.

PMID- 18809459
TI  - Matrix metalloproteinase-9 expression and release from skin fibroblasts
      interacting with keratinocytes: Upregulation in response to sulphur mustard.
AB  - Matrix metalloproteinases (MMPs), especially MMP-9 and MMP-2, degrade various
      proteins of the extracellular matrix, including collagen type IV the major
      component of basement membranes which also separate the epidermis from the
      dermis. Although previous work indicates the contribution of MMPs and their
      inhibitors (TIMPs) to the pathophysiology of skin lesions induced by the toxic
      chemical warefare agent sulphur mustard (SM), little is known about the
      underlying molecular and cellular mechanisms. In this study we demonstrate in a
      3D-skin model that topical application of SM significantly upregulated basal MMP
      9 mRNA expression and release from the cells as shown by qRT-PCR and zymography,
      whereas that of MMP-2, membrane-type 1 (MT1)-MMP, TIMP-1 and TIMP-2 remained
      almost unaffected by SM. Further studies in neonatal human dermal fibroblasts
      (NHDF) and HaCaT keratinocytes revealed that MMP-9 was not secreted from these
      cells, neither with or without exposure to SM. However, when NHDF and HaCaT were
      cocultivated, MMP-9 was expressed and released from the cell mixture, suggesting
      that interaction between both cell types is essential for MMP-9 production.
      Moreover, SM-treatment of NHDF/HaCaT cocultures further upregulated MMP-9
      biosynthesis and secretion, which was consistent with our findings obtained in
      the 3D-skin model. Addition of conditioned medium derived from SM-exposed HaCaT
      cells to NHDF was able to stimulate MMP-9 secretion and also increased the
      migratory potential of NHDF as shown in a scratch-wound healing assay and a
      fluorescent cell invasion assay. In contrast, culture supernatants of SM-treated
      NHDF had not such an effect on HaCaT cells. Taken together, our findings provide
      first evidence that SM exposure of skin stimulates keratinocytes to release
      soluble factors which in turn induce enhanced MMP-9 secretion and invasiveness of
      fibroblasts in vitro. This provides a potential mechanism probably contributing
      to SM-evoked tissue injury in vivo.

PMID- 18809460
TI  - Differential contributions of recognition factors of two plant lectins 
      Amaranthus caudatus lectin and Arachis hypogea agglutinin, reacting with Thomsen
      Friedenreich disaccharide (Galbeta1-3GalNAcalpha1-Ser/Thr).
AB  - Previous reports on the carbohydrate specificities of Amaranthus caudatus lectin
      (ACL) and peanut agglutinin (PNA, Arachis hypogea) indicated that they share the
      same specificity for the Thomsen-Friedenreich (T(alpha), Galbeta1-3GalNAcalpha1
      Ser/Thr) glycotope, but differ in monosaccharide binding--GalNAc>>Gal (inactive)
      for ACL; Gal>>GalNAc (weak) with respect to PNA. However, knowledge of the
      recognition factors of these lectins was based on studies with a small number
      monosaccharides and T-related oligosaccharides. In this study, a wider range of
      interacting factors of ACL and PNA toward known mammalian structural units,
      natural polyvalent glycotopes and glycans were examined by enzyme-linked
      lectinosorbent and inhibition assays. The results indicate that the main
      recognition factors of ACL, GalNAc was the only monosaccharide recognized by ACL
      as such, its polyvalent forms (poly GalNAcalpha1-Ser/Thr, Tn in asialo OSM) were
      not recognized much better. Human blood group precursor disaccharides Galbeta1
      3/4GlcNAcbeta (I(beta)/II(beta)) were weak ligands, while their clusters
      (multiantennary II(beta)) and polyvalent forms were active. The major recognition
      factors of PNA were a combination of alpha or beta anomers of T disaccharide and
      their polyvalent complexes. Although I(beta)/II(beta) were weak haptens, their
      polyvalent forms played a significant role in binding. From the 50% molar
      inhibition profile, the shape of the ACL combining site appears to be a cavity
      type and most complementary to a disaccharide of Galbeta1-3GalNAc (T), while the
      PNA binding domain is proposed to be Galbeta1-3GalNAcalpha or beta1--as the major
      combining site with an adjoining subsite (partial cavity type) for a
      disaccharide, and most complementary to the linear tetrasaccharide, Galbeta1
      3GalNAcbeta1-4Galbeta1-4Glc (T(beta)1-4L, asialo GM(1) sequence). These results
      should help us understand the differential contributions of polyvalent ligands,
      glycotopes and subtopes for the interaction with these lectins to binding, and
      make them useful tools to study glycosciences, glycomarkers and their biological
      functions.

PMID- 18809462
TI  - FGF-8 stimulates the expression of NR4A orphan nuclear receptors in osteoblasts.
AB  - Nurr1, NGFI-B, and Nor1 form the NR4A subfamily of orphan nuclear receptors. The
      NR4A receptors are immediate early genes that can be rapidly induced in response
      to a variety of stimuli in many cell types, for example, in osteoblasts. Nurr1
      regulates the differentiation of osteoblasts and the expression of several
      osteoblastic genes. Fibroblast growth factor 8b (FGF-8b) regulates osteoblastic
      differentiation. We show here that treatment of preosteoblastic MC3T3-E1 cells or
      mouse bone marrow mesenchymal cells with FGF-8b induces the expression of NR4A
      receptors rapidly and in a dose-dependent manner. This induction involves mitogen
      activated protein kinase (MAPK), phosphatidylinositol-3-kinase (PI-3K), and
      protein kinase C (PKC) pathways. FGF-8b stimulates the proliferation of MC3T3-E1
      cells. This effect is enhanced by overexpression of Nurr1 and NGFI-B whereas it
      is abolished by a dominant negative Nurr1 variant. In conclusion, FGF-8b induces
      the expression of NR4A orphan nuclear receptors that are involved in mediating
      the growth promoting effect of FGF-8b in osteoblasts.

PMID- 18809463
TI  - Neuroprotective effect of hydroxytyrosol and hydroxytyrosol acetate in rat brain
      slices subjected to hypoxia-reoxygenation.
AB  - Hydroxytyrosol (HT) and hydroxytyrosol acetate (HT-AC) are two well-known
      phenolic compounds with antioxidant properties that are present in virgin olive
      oil (VOO). Because VOO has shown neuroprotective effects in rats, the purpose of
      the present study was to investigate the possible neuroprotective effect of HT
      and HT-AC in a model of hypoxia-reoxygenation in rat brain slices after in vitro
      incubation of these compounds or after 7 days of oral treatment with 5 or 10
      mg/kg per day. Lactate dehydrogenase (LDH) efflux to the incubation medium was
      measured as a marker of brain cell death. HT and HT-AC inhibited LDH efflux in a
      concentration-dependent manner, with 50% inhibitory concentrations of 77.78 and
      28.18 microM, respectively. Other well-known antioxidants such as vitamin E and N
      acetyl-cysteine had no neuroprotective effect in this experimental model. After 1
      week of treatment, HT (5 and 10 mg/kg per day p.o.) reduced LDH efflux by 37.8%
      and 52.7%, respectively, and HT-AC reduced LDH efflux by 45.4% and 67.8%. These
      data are additional evidence of the cytoprotective effect of VOO administration,
      and provide a preliminary basis for further study of these polyphenols as
      potential neuroprotective compounds.

PMID- 18809461
TI  - The energy hypothesis of sleep revisited.
AB  - One of the proposed functions of sleep is to replenish energy stores in the brain
      that have been depleted during wakefulness. Benington and Heller formulated a
      version of the energy hypothesis of sleep in terms of the metabolites adenosine
      and glycogen. They postulated that during wakefulness, adenosine increases and
      astrocytic glycogen decreases reflecting the increased energetic demand of
      wakefulness. We review recent studies on adenosine and glycogen stimulated by
      this hypothesis. We also discuss other evidence that wakefulness is an energetic
      challenge to the brain including the unfolded protein response, the electron
      transport chain, NPAS2, AMP-activated protein kinase, the astrocyte-neuron
      lactate shuttle, production of reactive oxygen species and uncoupling proteins.
      We believe the available evidence supports the notion that wakefulness is an
      energetic challenge to the brain, and that sleep restores energy balance in the
      brain, although the mechanisms by which this is accomplished are considerably
      more complex than envisaged by Benington and Heller.

PMID- 18809464
TI  - Odour of limonene affects feeding behaviour in the blowfly, Phormia regina.
AB  - Experiences of odours at meals are thought to affect food preference in many
      animals. To study appetite modulation by odours, we established a new
      experimental system based on the modification of a previous method, where flies
      fed sucrose flavoured with D-limonene subsequently showed reduced appetite to
      plain sucrose. In this new experimental system, a fly population was divided into
      two groups: (1) the "simultaneous" group of flies was exposed to D-limonene and
      sucrose simultaneously for 10 min, and (2) the "separate" group of flies was
      exposed to sucrose alone for 10 min, and 1h later, to limonene for 10 min. The
      appetite of flies in the "separate" group for sucrose was unaffected by the
      experiment, but the appetite of flies in the "simultaneous" group was
      significantly decreased, and this effect lasted for > or = 3 days. To investigate
      if this appetite modulation by D-limonene was based on long-term memory formation
      (protein synthesis), we examined the effects of the protein synthesis inhibitor,
      cycloheximide. Injection of cycloheximide 1h after exposure to limonene and
      sucrose inhibited the appetite suppression in the "simultaneous" group of flies.
      In addition, to exclude the possibility that D-limonene exerted its effect
      through taste, rather than odour, we examined the effect of removing of the
      olfactory organs, antennae and maxillary palps on appetite modulation by D
      limonene. When the olfactory organs were removed, no reduction in appetite was
      observed in the flies in the "simultaneous" group, indicating olfaction. In our
      new and effective appetite-modulation system for flies, modulation of appetite by
      olfactory detection of D-limonene was shown.

PMID- 18809465
TI  - Species-specific anti-apoptotic activity of cellular prion protein in a mouse PrP
      deficient neuronal cell line transfected with mouse, hamster, and bovine Prnp.
AB  - The neuroprotective function of prion protein (PrP) was revealed first by the
      fact that reintroduction of the mouse prion protein gene (Prnp) into a mouse
      Prnp(-/-) neuronal cell line, HpL3-4, could prevent apoptosis induced by serum
      deprivation. In the present study, the anti-apoptotic activities of mouse,
      hamster, and bovine PrP were compared by expressing mouse PrP (MoPrP), hamster
      PrP (HaPrP), and bovine PrP (BoPrP) in HpL3-4 cells, respectively. Morphological
      analysis and DNA fragmentation assays demonstrated that HpL3-4 cells expressing
      HaPrP, BoPrP, and empty vector (EM) showed the typical features of apoptosis with
      DNA laddering and apoptotic bodies after serum deprivation, whereas HpL3-4 cells
      expressing MoPrP showed decreased levels of apoptosis in comparison. The levels
      of histone-associated DNA fragments (mono- and oligonucleosomes) in the cytosol
      fractions of the cells correlated with the levels of DNA laddering. These results
      indicate a species-specific anti-apoptotic function of PrP exists, suggesting
      that the interaction of the mouse PrP with mouse host factors is required for its
      anti-apoptotic activity.

PMID- 18809466
TI  - Establishment of human cell lines showing circadian rhythms of bioluminescence.
AB  - We have established human retinal pigment epithelial cell lines stably expressing
      the luciferase gene, driven by the human Bmal1 promoter, to obtain human-derived
      cells that show circadian rhythms of bioluminescence after dexamethasone
      treatment. The average circadian period of bioluminescence for the obtained
      clones was 24.07+/-0.48 h. Lithium (10 mM) in the medium significantly lengthened
      the circadian period of bioluminescence, which is consistent with previous
      reports, while 2 mM or 5 mM lithium had no effect. This is the first report on
      the establishment of human-derived cell lines that proliferate infinitely and
      show circadian rhythms of bioluminescence, and also the first to investigate the
      effects of low-dose lithium on the circadian rhythms of human-derived cells in
      vitro. The established cells will be useful for various in vitro studies of human
      circadian rhythms and for the development of new therapies for human disorders
      related to circadian rhythm disturbances.

PMID- 18809467
TI  - Atomic force microscopy, biochemical analysis of 3T3-L1 cells differentiated in
      the absence and presence of insulin.
AB  - BACKGROUND: There are ample evidences to demonstrate that differentiation of
      preadipocytes is associated with deposition of fat in cells. Still, it is unclear
      whether the differentiation process also alters membrane topology as well as
      cholesterol levels and whether insulin contributes to it. METHODS: Membrane
      scanning of differentiated cells, along with freshly plated and 11 day
      preadipocytes, was performed using Atomic Force Microscopy (AFM) to gain
      qualitative information about cell surface properties as well as roughness.
      Moreover, glucose uptake, lipid analysis, expression profiling of transcription
      factors and signaling molecules involved in the process of differentiation was
      also performed. RESULTS: We report (i) differentiation in the presence of 500
      microM isobutylmethylxanthine (IBMX), 0.25 microM dexamethasone (DEX) with or
      without 0.1 microM (0.57 microg/ml) insulin directly alters membrane topology.
      (ii) At nano-levels, addition of insulin maintains plasma membrane roughness
      during differentiation in comparison with IBMX and DEX only. (iii) At macro
      levels, decreased fat accumulation in preadipocytes exposed to insulin during the
      initial stages of differentiation is a result of reduced expression and nuclear
      localization of sterol regulatory element binding protein (SREBP)-1. GENERAL
      SIGNIFICANCE: This study reports a significant reduction of membrane cholesterol
      and total cholesterol (p<0.01) in cells differentiated in the presence of
      insulin.

PMID- 18809468
TI  - Toll-like receptor signaling in endogenous neuroprotection and stroke.
AB  - Stroke and other cerebral vascular diseases are a leading cause of morbidity and
      mortality in the United States. Despite intensive research to identify
      interventions that lessen cerebrovascular injury, no major therapies exist.
      Development of stroke prophylaxis involves an understanding of the mechanisms of
      damage following cerebral ischemia, and elucidation of the endogenous mechanisms
      that combat further brain injury. Toll-like receptors (TLRs) are critical
      components of the innate immune system that have been shown recently to mediate
      ischemic injury. Paradoxically, TLR ligands administered systemically induce a
      state of tolerance to subsequent ischemic injury. Herein we suggest that
      stimulation of TLRs prior to ischemia reprograms TLR signaling that occurs
      following ischemic injury. Such reprogramming leads to suppressed expression of
      pro-inflammatory molecules and enhanced expression of numerous anti-inflammatory
      mediators that collectively confer robust neuroprotection. Our findings indicate
      that numerous preconditioning stimuli lead to TLR activation, an event that
      occurs prior to ischemia and ultimately leads to TLR reprogramming. Thus genomic
      reprogramming of TLR signaling may be a unifying principle of tolerance to
      cerebral ischemia.

PMID- 18809469
TI  - Proteolytic activity during cortical development is distinct from that involved
      in hypoxic ischemic injury.
AB  - Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases
      involved in brain development and the etiology of adult cerebral injuries. In
      this study, we determined the MMP-2 and 9 responses following hypoxic ischemia
      (HI) injury in the developing brain. First, we characterized the developmental
      changes of MMP activity in the rat brain from embryonic day 18 (E18) to postnatal
      day 120 (P120). MMP-2 activity was high from E18 to P3 and decreased with age (P<
      or =0.001), while MMP-9 activity was not detectable. MMP-2 immunoreactivity was
      closely associated with differentiating cortical plate and subplate neurons.
      Next, we characterized the proteolytic changes after unilateral HI brain injury
      in 3- (P3) and 21- (P21) day-old rats. Zymography revealed that in the P21 rat
      brain, MMP-9 activity (150 and 92 kDa forms) was increased at 6 h and remained
      elevated 24 h post-injury in the ipsilateral injured hemisphere (P< or =0.001),
      whereas there was a gradual increase in MMP-2 (65 kDa) activity, reaching a peak
      at 5 days (P< or =0.001). Similarly, quantitative real time polymerase chain
      reaction (qRT-PCR) indicated significant elevations in MMP-9 and MMP-2 mRNA
      expression in the injured cortex (P< or =0.05) and hippocampus (P< or =0.05) at 1
      and 5 days post-injury, respectively in the P21 rat brain. In the P3 rat brain,
      zymography results revealed that both pro (92 kDa) and cleaved (87 kDa) MMP-9
      activities were upregulated in the ipsilateral injured hemisphere from 6 h to 1
      day after injury (P< or =0.001). In contrast, cleaved MMP-2 (60 kDa) was only
      moderately upregulated at 6 h (P< or =0.01), while pro MMP-2 (65 kDa) levels were
      unaffected. MMP-9 mRNA expression was also increased at 6 h (P< or =0.05)
      following injury at P3, whereas MMP-2 expression remained unchanged compared with
      the uninjured contralateral hemisphere. Immunohistochemistry indicated that MMP-9
      protein expression was localized predominantly to neurons and peri-vascular
      astrocytes in the affected regions at early time points, whereas MMP-2 was
      present on reactive astrocytes surrounding the infarct at later time points.
      Together, these results indicate that MMP-2 may be primarily associated with the
      development and differentiation of cortical plate neurons and wound recovery
      processes. Conversely, MMP-9 appeared to be associated with more acute processes
      during the period of lesion development.

PMID- 18809470
TI  - Abnormal response of melanin-concentrating hormone deficient mice to fasting:
      hyperactivity and rapid eye movement sleep suppression.
AB  - Melanin-concentrating hormone (MCH) is a hypothalamic neuropeptide that has been
      implicated in energy homeostasis. Pharmacological studies with MCH and its
      receptor antagonists have suggested additional behavioral roles for the
      neuropeptide in the control of mood and vigilance states. These suggestions have
      been supported by a report of modified sleep in the MCH-1 receptor knockout
      mouse. Here we found that MCH knockout (MCH(-)(/)(-)) mice slept less during both
      the light and dark phases under baseline conditions. In response to fasting, MCH(
      )(/)(-) mice exhibited marked hyperactivity, accelerated weight loss and an
      exaggerated decrease in rapid eye movement (REM) sleep. Following a 6-h period of
      sleep deprivation, however, the sleep rebound in MCH(-)(/)(-) mice was normal.
      Thus MCH(-)(/)(-) mice adapt poorly to fasting, and their loss of bodyweight
      under this condition is associated with behavioral hyperactivity and abnormal
      expression of REM sleep. These results support a role for MCH in vigilance state
      regulation in response to changes in energy homeostasis and may relate to a
      recent report of initial clinical trials with a novel MCH-1 receptor antagonist.
      When combined with caloric restriction, the treatment of healthy, obese subjects
      with this compound resulted in some subjects experiencing vivid dreams and sleep
      disturbances.

PMID- 18809471
TI  - The influence of acute and chronic administration of 1,2-dimethyl-6,7-dihydroxy
      1,2,3,4-tetrahydroisoquinoline on the function of the nigrostriatal dopaminergic
      system in rats.
AB  - The contribution of (R)-enantiomer of N-methyl-salsolinol (1,2-dimethyl-6,7
      dihydroxy-1,2,3,4-tetrahydroisoquinoline; NMSal) to the degeneration of
      dopaminergic neurons in the course of Parkinson's disease (PD) has been
      predominantly suggested by in vitro experiments in cell culture and by an in vivo
      study in which this compound has been directly injected into the rat striatum.
      The aim of the present study was to examine the effects of racemic NMSal (50 and
      100 mg/kg) administered systemically, acutely and chronically for 21 days to
      rats, on the neurochemical and behavioral markers of PD. Our results showed that
      racemic NMSal easily penetrated the blood-brain barrier. Its brain level was
      relatively high 2-6 h after a single injection than gradually decreased. NMSal
      was quickly eliminated from the rat brain, its concentration 24 h after
      withdrawal from chronic treatment was very low. NMSal at both examined doses did
      not affect striatal and nigral levels of dopamine (DA) 2 h after the first and
      last chronic injections, however, it markedly changed DA catabolism. In the
      striatum both its doses evoked a significant acceleration of the total and
      oxidative, monoamine oxidase (MAO)-dependent DA catabolism without affecting the
      catechol-O-methyltransferase (COMT)-dependent O-methylation. In the substantia
      nigra (SN), only the higher dose of NMSal produced such effect. DA catabolism in
      either structure was the same as in control 24 h after cessation of chronic
      treatment. The second characteristic marker of PD, the number of tyrosine
      hydroxylase-immunoreactive (TH-ir) neurons in the SN, was not affected by chronic
      NMSal treatment as revealed by the stereological counting. In the behavioral
      study, it was found that racemic NMSal significantly suppressed spontaneous
      locomotor activity and effectively prevented that stimulated by apomorphine. Our
      results suggest that NMSal may play an important role in the regulation of
      dopaminergic activity rather than in inducing changes of parkinsonian type.

PMID- 18809472
TI  - Protein kinase C-dependent and independent signaling pathways regulate synaptic
      GluR1 and GluR4 AMPAR subunits during in vitro classical conditioning.
AB  - Protein kinase C (PKC) signal transduction pathways have been implicated in
      mechanisms of synaptic plasticity and learning, however, the roles of the
      different PKC family isoforms remain to be clarified. Previous studies showed
      that NMDAR-mediated trafficking of GluR4-containing AMPARs supports conditioning
      and that the mitogen-activated protein kinases (MAPKs) have a central role in the
      synaptic delivery of GluR4 subunits. Here, an in vitro model of classical
      conditioning in pond turtles, Pseudemys scripta elegans, was used to assess the
      role of PKC isoforms in mechanisms underlying this form of learning. We show that
      the PKC antagonists chelerythrine and bisindolylmaleimide I attenuated
      conditioned response (CR) acquisition and expression, as did the PKCzeta
      pseudosubstrate peptide inhibitor ZIP. Analysis of protein expression revealed
      that PKCzeta is activated in early stages of conditioning followed shortly
      afterward by increased levels of PKCalpha/beta and activation of ERK MAPK. Data
      also suggest that PKCzeta is upstream from and activates ERK. Finally, protein
      localization studies using confocal imaging indicate that inhibitors of ERK, but
      not PKC, suppress colocalization of GluR1 with synaptophysin while inhibitors of
      PKC and ERK attenuate colocalization of GluR4 with synaptophysin. Together, these
      data suggest that acquisition of conditioning proceeds by two stages of AMPAR
      trafficking. The first is PKC-independent and ERK-dependent synaptic delivery of
      GluR1 subunits to activate silent synapses. This is followed by PKC-dependent and
      ERK-dependent synthesis and delivery of GluR4 subunits that supports the
      acquisition of CRs. Therefore, there is a selective role for PKC and MAPK
      signaling pathways in multistep AMPAR trafficking that mediates acquisition of
      classical conditioning.

PMID- 18809474
TI  - Branch-length estimation bias misleads molecular dating for a vertebrate
      mitochondrial phylogeny.
AB  - Despite recent methodological advances in inferring the time-scale of biological
      evolution from molecular data, the fundamental question of whether our
      substitution models are sufficiently well specified to accurately estimate branch
      lengths has received little attention. I examine this implicit assumption of all
      molecular dating methods, on a vertebrate mitochondrial protein-coding dataset.
      Comparison with analyses in which the data are RY-coded (AG --> R; CT --> Y)
      suggests that even rates-across-sites maximum likelihood greatly under
      compensates for multiple substitutions among the standard (ACGT) NT-coded data,
      which has been subject to greater phylogenetic signal erosion. Accordingly, the
      fossil record indicates that branch-lengths inferred from the NT-coded data
      translate into divergence time overestimates when calibrated from deeper in the
      tree. Intriguingly, RY-coding led to the opposite result. The underlying NT and
      RY substitution model misspecifications likely relate respectively to "hidden"
      rate heterogeneity and changes in substitution processes across the tree, for
      which I provide simulated examples. Given the magnitude of the inferred molecular
      dating errors, branch-length estimation biases may partly explain current
      conflicts with some palaeontological dating estimates.

PMID- 18809473
TI  - Selective lesion of septal cholinergic neurons in rats impairs acquisition of a
      delayed matching to position T-maze task by delaying the shift from a response to
      a place strategy.
AB  - This study tested the hypothesis that septal cholinergic lesions impair
      acquisition of a delayed matching to position (DMP) T-maze task in male rats by
      affecting learning strategy. Rats received either the selective cholinergic
      immunotoxin, 192 IgG-saporin (SAP) or artificial cerebrospinal fluid directly
      into the medial septum. Two weeks later, animals were trained to acquire the DMP
      task. SAP-treated rats took significantly longer to acquire the task than
      corresponding controls. Both SAP-treated and control rats adopted a persistent
      turn and utilized a response strategy during early periods of training. By the
      time rats reached criterion the persistent turn was no longer evident, and all
      rats had shifted to an allocentric strategy, i.e., were relying on extramaze cues
      to a significant degree. During the acquisition period, SAP-treated rats spent
      significantly more days showing a persistent turn and using a response strategy
      than corresponding controls. The added time spent using a response strategy
      accounted entirely for the added days required to reach criterion among the SAP
      treated rats. This suggests that the principal mechanism by which septal
      cholinergic lesions impair DMP acquisition in male rats is by increasing the
      predisposition to use a response vs. a place strategy, thereby affecting the
      ability to switch from one strategy to another.

PMID- 18809475
TI  - Membrane docking of an aggregation-prone protein improves its solubilization.
AB  - We used preS2-S'-beta-galactosidase, a three domain fusion protein that
      aggregates extensively at 43 degrees C in the cytoplasm of Escherichia coli to
      search for multicopy suppressors of protein aggregation and inclusion bodies
      formation, and took advantage of the known differential solubility of preS2-S'
      beta-galactosidase at 37 and 43 degrees C to develop a selection procedure for
      the gene products that would prevent its aggregation in vivo at 43 degrees C.
      First, we demonstrate that the differential solubility of preS2-S'-beta
      galactosidase results in a lactose-positive phenotype at 37 degrees C as opposed
      to a lactose-negative phenotype at 43 degrees C. We searched for multicopy
      suppressors of preS2-S'-beta-galactosidase aggregation at 43 degrees C by
      selecting pink lactose-positive colonies on a background of white lactose
      negative colonies after transformation of bacteria with an E. coli gene bank. We
      found only two multicopy suppressors of preS2-S'-beta-galactosidase aggregation
      at 43 degrees C, protein isoaspartate methyltransferase (PIMT) and the membrane
      components ChbBC of the N,N'-diacetylchitobiose phosphotransferase transporter.
      We have previously shown that PIMT overexpression reduces the level of
      isoaspartate in preS2-S'-beta-galactosidase, increases its thermal stability and
      consequently helps in its solubilization at 43 degrees C (Kern et al., J.
      Bacteriol. 187, 1377-1383). In the present work, we show that ChbBC
      overexpression targets a fraction of preS2-S'-beta-galactosidase to the membrane,
      and decreases its amount in inclusion bodies, which results in its decreased
      thermodenaturation and in a lactose-positive phenotype at 43 degrees C. Cross
      linking experiments show that the inner membrane protein ChbC interacts with
      preS2-S'-beta-galactosidase. Our results suggest that membrane docking of
      aggregation-prone proteins might be a useful method for their solubilization.

PMID- 18809476
TI  - An FDA perspective on the nonclinical use of the X-Omics technologies and the
      safety of new drugs.
AB  - Work in the field "omics" (toxicogenomics, proteomics, and metabolomics) has
      exploded. It is hoped that 'omics' could be a tool for evaluation of general
      toxicology, reproductive toxicology, the carcinogenicity potential of
      pharmaceuticals and several other types of toxicity, eventually replacing the use
      of animals. Although much progress has been made in the standardization of
      procedures, challenges remain for evaluation of pharmaceuticals for regulatory
      purposes, because of off-target toxicologic effects, as well as issues of
      interpretation and the large number of biologic variables that can affect
      results. Such variables include species/strain, genetic variations, diet, age,
      dose, duration, and weight of animals. These variables also confound database
      compilations of expression profiles. The most promising use in the near future
      would be to clarify pathways for the various types of toxicity and
      carcinogenicity and get biomarkers for these pathways, to help assess relevance
      of nonclinical findings to humans.

PMID- 18809477
TI  - Activation of the protein p7OS6K via ERK phosphorylation by cholinergic
      muscarinic receptors stimulation in human neuroblastoma cells and in mice brain.
AB  - Stimulation of cholinergic muscarinic receptors has been shown to provide
      substantial protection from DNA damage, oxidative stress and mitochondrial
      impairment, insults that may be encountered by neurons in development, aging, or
      neurodegenerative diseases. A study recently indicated that the activation of
      muscarinic receptors in astrocytoma cells modified the expression of the kinase
      p70S6K involved in the translational control. The translational control is in
      part regulated by a cascade of phosphorylation affecting proteins of the anti
      apoptotic way controlled by mTOR (mammalian target of rapamycin) and the pro
      apoptotic way controlled by PKR. The aim of our study was to investigate the
      effect of cholinergic muscarinic stimulation by an agonist oxotremorine on the
      anti-apoptotic way of translational control, in human neuroblastoma cells and in
      mice brain. Our results showed that muscarinic receptor activation significantly
      increased the expression of phosphorylated p70S6K, eIF4E and ERK without
      modification of mTOR activity in neuroblastoma cells and in cerebral cortex and
      hippocampus of mice, suggesting a stimulation of protein synthesis. Our findings
      support the notion that synaptic activity, through activation of neurotransmitter
      receptors, can provide substantial support of cellular survival mechanisms and
      suggest that loss of such synaptic input increases vulnerability to insult
      induced programmed cell death.

PMID- 18809478
TI  - Network structure and macromolecular drug release from poly(vinyl alcohol)
      hydrogels fabricated via two crosslinking strategies.
AB  - Injectable hydrogels have potential biomedical applications ranging from tissue
      fillers to drug delivery vehicles. This study focussed on evaluating the
      structure of poly(vinyl alcohol) (PVA) hydrogels of variable solid content and
      high molecular weight model drug release from the networks formed via either
      conventional photo-polymerization compared with chemical initiation of
      polymerization using an oxidation-reduction (redox) reaction. Swelling behaviour
      was characterised in water to assess the structural properties. Model drugs, FITC
      Dextran, 20 kDa (FD20) and 4 kDa (FD4) were loaded in the hydrogels prior to
      curing and drug release studies conducted. Redox-cured hydrogels were more
      swollen than UV-cured systems, lost approximately 20% of their polymer mass
      compared to only 5% from UV-cured hydrogels and subsequently exhibited networks
      of larger mesh sizes. Also, networks of variable solid contents showed different
      structural properties with systems of higher polymer concentration exhibiting a
      smaller mesh size. The difference in structural properties of the networks
      affected release of FD20, being faster in redox-cured than UV-cured hydrogels,
      and slower from systems of higher solid content. Release of FD4 was faster than
      FD20 from networks of same solid content. This study suggested that PVA hydrogels
      can be cured by redox-initiation to function as a controlled delivery system for
      macromolecular drugs.

PMID- 18809479
TI  - Intestinal first-pass glucuronidation activities of selected dihydroxyflavones.
AB  - Flavonoids have low bioavailabilities due to extensive intestinal first-pass
      metabolisms, especially glucuronidation. The present study aimed to evaluate the
      intestinal glucuronidation of dihydroxyflavones and provide more information on
      their structure-activity relationships. Seven dihydroxyflavones, namely 3,7-, 5,7
      , 6,7-, 7,8-, 2',7-, 3',7-, and 4',7-dihydroxyflavone and a monohydroxyflavone, 7
      hydroxyflavone, were investigated by incubating each hydroxyflavone at various
      concentrations with either human jejunum microsome or rat intestinal microsome.
      Two mono-glucuronides were identified for each dihydroxyflavone. For human
      jejunum microsome, most of the studied dihydroxyflavones demonstrated greater
      glucuronidation activities than that of 7-hydroxyflavone except for 3,7
      dihydroxyflavone and 4',7-dihydroxyflavone. 3',7-dihydroxyflavone had the
      greatest intrinsic clearance which was at least seven times greater than that of
      all other dihydroxyflavones. In addition, species difference in glucuronidation
      activity was observed with human jejunum microsome higher than rat intestinal
      microsome for all hydroxyflavones except for 3,7-dihydroxyflavone. The results
      further demonstrated that the hydroxyl group positions do affect the intestinal
      glucuronidation activity of hydroxyflavones. Increasing the number of hydroxyl
      groups on A- or B-ring (except for 4'-OH) would enhance the glucuronidation
      activity of flavones, whereas adding a 3-OH on C-ring might not. Furthermore,
      existence of hydroxyl group at 3' position may enhance the glucuronidation
      activity of flavonoids.

PMID- 18809480
TI  - Thermosensitivity and release from poly N-isopropylacrylamide-polylactide
      copolymers.
AB  - A series of thermoresponsive-co-biodegradable polymers, containing varying molar
      ratios of N-isopropylacrylamide (NIPA) and poly-lactic acid diacrylate macromer
      (PLAM) were prepared and characterised. Chemical structures were confirmed by
      nuclear magnetic resonance (NMR) and Fourier transform infrared (FTIR). The
      hydrogels were thermoresponsive, exhibiting an increase in the lower critical
      solution temperature (LCST) the higher the percent of PLAM present. Swelling
      properties were dependant on both temperature and PLAM content. The degradation
      behaviour of the three-dimensional polymeric networks formed was dependent on
      both structural (mesh size, molecular weight distribution, composition) and
      environmental parameters (temperature). Swelling and in vitro biodegradation
      induced morphological structural changes were examined using scanning electron
      microscopy (SEM). A greater rate of degradation and disruption to the porous
      network could be seen with increasing lactide content. Degradation was faster
      below the LCST, demonstrated by FTIR, pH decrease and acid release, consistent
      with the increased hydrophilicity of the network. The release profiles of the
      model drug indomethacin (IDM), from these thermoresponsive-co-biodegradable
      polymers, were found to be dependant on copolymer composition, drug loading and
      temperature, more rapid release occurring below the LCST.

PMID- 18809481
TI  - Effect of polyols on polyethylene glycol (PEG)-induced precipitation of proteins:
      Impact on solubility, stability and conformation.
AB  - Effect of polyols on the solubility of bovine serum albumin (BSA) in the presence
      of polyethylene glycols (PEGs) was investigated in order to strengthen the
      understanding of the observed effects of polyols and PEGs on protein properties
      in solution. Effect of polyols and/or PEGs on the thermodynamic (conformational)
      stability of BSA was measured using DSC and circular dichroism (CD). Glucose,
      sucrose, raffinose, glycerol and sorbitol, all reduced the extent of protein
      precipitation. Solubility of BSA in the presence of ethylene glycol increased in
      the case of PEG 1450 and PEG 8000, but was unaffected in the case of PEG 400. DSC
      studies indicated that smaller PEGs have destabilizing influence on protein
      structure. CD studies showed that smaller PEGs (ethylene glycol) induce subtle
      unfolding while stabilizing polyols induce subtle compaction. Results show that,
      effect of polyols on the apparent solubility of the protein correlates with their
      effect on the thermodynamic stability of the protein, smaller PEGs are not
      appropriate for estimating the activity of proteins in saturated solutions, and
      subtle changes in protein conformation can significantly affect protein
      precipitation. Though smaller PEGs have weak attractive interactions with protein
      molecules, perturbation of protein structure by PEGs can be balanced by utilizing
      appropriate stabilizing solutes.

PMID- 18809482
TI  - Spontaneous hair cell regeneration in the mouse utricle following gentamicin
      ototoxicity.
AB  - Whereas most epithelial tissues turn-over and regenerate after a traumatic
      lesion, this restorative ability is diminished in the sensory epithelia of the
      inner ear; it is absent in the cochlea and exists only in a limited capacity in
      the vestibular epithelium. The extent of regeneration in vestibular hair cells
      has been characterized for several mammalian species including guinea pig, rat,
      and chinchilla, but not yet in mouse. As the fundamental model species for
      investigating hereditary disease, the mouse can be studied using a wide variety
      of genetic and molecular tools. To design a mouse model for vestibular hair cell
      regeneration research, an aminoglycoside-induced method of complete hair cell
      elimination was developed in our lab and applied to the murine utricle. Loss of
      utricular hair cells was observed using scanning electron microscopy, and
      corroborated by a loss of fluorescent signal in utricles from transgenic mice
      with GFP-positive hair cells. Regenerative capability was characterized at
      several time points up to six months following insult. Using scanning electron
      microscopy, we observed that as early as two weeks after insult, a few immature
      hair cells, demonstrating the characteristic immature morphology indicative of
      regeneration, could be seen in the utricle. As time progressed, larger numbers of
      immature hair cells could be seen along with some mature cells resembling surface
      morphology of type II hair cells. By six months post-lesion, numerous regenerated
      hair cells were present in the utricle, however, neither their number nor their
      appearance was normal. A BrdU assay suggested that at least some of the
      regeneration of mouse vestibular hair cells involved mitosis. Our results
      demonstrate that the vestibular sensory epithelium in mice can spontaneously
      regenerate, elucidate the time course of this process, and identify involvement
      of mitosis in some cases. These data establish a road map of the murine
      vestibular regenerative process, which can be used for elucidating the molecular
      events that govern this process.

PMID- 18809483
TI  - Plants used as remedies antirheumatic and antineuralgic in the traditional
      medicine of Lebanon.
AB  - AIM OF THE STUDY: In the present investigation, ethnobotanical and
      ethnopharmacological research of the traditional use of plants to cure
      antirheumatic and antineuralgic diseases was carried out in Lebanon. MATERIALS
      AND METHODS: The information was collected from different cities and villages of
      the twenty-six districts "aqdya or qadaa" of the six governorates "mohaafazah" of
      Lebanon. The knowledge on the medicinal use of plants has been recorded directly
      on the basis of a detailed survey on herbalists "Attarin or dabbous", folk
      healers, on older experienced people and midwives "daye". This research was
      carried out for 5 years (2002-2007). RESULTS AND CONCLUSIONS: In this survey, 231
      species of which 5 are endemic, distributed in 79 botanical families, currently
      used as antirheumatic herbal remedies, were collected and identified. Among them
      53.3% are indigenous, 19.2% are cultivated and 17.5% are imported. Their latin
      names, local names, local medicinal uses, the used parts of the plant and the
      preparations and the ways of administration are described. The anti-inflammatory
      properties due to the plant compounds have been demonstrated and discussed.

PMID- 18809484
TI  - Aegiceras corniculatum extract suppresses initial and late phases of inflammation
      in rat paw and attenuates the production of eicosanoids in rat neutrophils and
      human platelets.
AB  - AIM OF THE STUDY: The present study is designed to explore the anti-inflammatory
      potential of Aegiceras corniculatum Linn. Blanco stems extracts and their
      mechanism of action against various pro-inflammatory mediators and to validate
      its traditional use against inflammatory diseases. MATERIALS AND METHODS: Rat paw
      edema and peritonitis models were employed for in vivo studies. For in vitro
      studies human platelets and rat neutrophils were stimulated with Ca(2+)-ionophore
      A23187 leading to the production of various pro-inflammatory metabolites, i.e.,
      12-HTT, 12-HETE and LTB(4) and 5-HETE which were quantified by HPLC. RESULTS: The
      highly polar methanol extract (100mg/kg) caused approximately 90% reduction in
      the carrageenan- and prostaglandin E2-induced paw edema in rats. It also caused
      the inhibition of cycloxygenase-1 metabolite, 12-HHT (IC(50) 41.1+/-1.5microg/ml)
      with a concomitant rise in 12-lipoxygenase metabolite, 12-HETE in A23187
      stimulated human platelets. Conversely, the non-polar hexane extract attenuated
      (IC(50) 0.36+/-0.12microg/ml) 12-HETE formation with a parallel rise in 12-HHT,
      thereby displaying a selectivity towards 12-lipoxygenase. Non-polar hexane
      extract also antagonized the production of 5-lipoxygenase metabolites, i.e.,
      leukotriene B(4) and 5-HETE in the rat neutrophils. Furthermore, ethyl acetate
      extract inhibited both COX and 5-LOX with a marked decline in the production of
      12-HHT (IC(50) 0.08+/-0.002microg/ml) and LTB(4) (IC(50) 0.86+/-0.03microg/ml),
      respectively. The anti-inflammatory effect of hexane and ethyl acetate extracts
      was also reflected by the diminution of carrageenan-induced cell infiltration in
      rat peritoneum. Additionally, plant extracts caused approximately 60% suppression
      in dextran-induced paw edema implying that they also ameliorate histamine and
      serotonin release. CONCLUSION: Hexane, ethyl acetate and methanol extracts
      derived from Aegiceras corniculatum possess significant anti-inflammatory
      activity via multiple mechanisms and validate their traditional use against
      inflammation-related diseases.

PMID- 18809485
TI  - In vitro anti-HIV-1 properties of ethnobotanically selected South African plants
      used in the treatment of sexually transmitted diseases.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: [corrected The plants selected in this study are
      used traditionally in the treatment of sexually transmitted diseases and
      traditional healers interviewed claimed these plants can also help AIDS patients.
      AIM: To evaluating the in vitro anti-HIV properties of selected plants in various
      bioassays. MATERIALS AND METHODS: The extracts were evaluated for their
      inhibition against alpha-glycohydrolase, reverse transcriptase and viral proteins
      (NF-kappaB and Tat) which play a significant role in the HIV life cycle. RESULTS:
      Terminalia sericea extract (IC(50)=92mg/ml) exhibited a considerable alpha
      glucosidase inhibitory activity which was better than acarbose (IC(50)=131mg/ml)
      under our assay conditions. In the reverse transcriptase assay, T. sericea also
      showed good inhibitory activity (IC(50)=43mg/ml), which was higher than that of
      the reference drug, Adriamycin (IC(50)=100mg/ml). The ethyl acetate extract of
      Elaeodendron transvaalense exhibited the most potent inhibitory activity in both
      the NF-kappaB and Tat assays with inhibitory activity of 76% and 75% respectively
      at a concentration of 15mg/ml. The acetone and chloroform extracts of E.
      transvaalense and Zanthoxylum davyi also showed good activity in the NF-kappaB
      and Tat assays.

PMID- 18809486
TI  - Effects of South African traditional medicine in animal models for depression.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The four South African medicinal plants
      Agapanthus campanulatus (AC), Boophone distica (BD), Mondia whitei (MW) and
      Xysmalobium undulatum (XU) are used in traditional medicine to treat depression.
      AIM: To evaluate the effect of ethanolic extracts of the plants in models for
      depression. MATERIALS AND METHODS: The extracts were screened for affinity for
      the serotonin transporter (SERT) in the [(3)H]-citalopram-binding assay. The
      inhibitory potency of the extracts towards the SERT, the noradrenalin transporter
      (NAT) and the dopamine transporter (DAT) were determined in a functional uptake
      inhibition assay. Antidepressant-like effects of the extracts were investigated
      using the tail suspension test (TST) and the forced swim test in both rats (rFST)
      and mice (mFST). RESULTS: All four plants showed affinity for SERT in the binding
      assay. AC and BD showed functional inhibition of SERT, NAT and DAT, MW affected
      SERT while XU showed no effect. BD showed significant effect in the TST and in
      the mFST/rFST, AC showed significant effect in mFST, MW showed significant effect
      in the rFST and XU showed significant effect in the mFST. CONCLUSION: In this
      study we have demonstrated the antidepressant activity of four South African
      medicinal plants in vitro and in vivo, supporting their rational use in
      traditional medicine.

PMID- 18809487
TI  - Human skin stem cells and the ageing process.
AB  - In healthy individuals, skin integrity is maintained by epidermal stem cells
      which self-renew and generate daughter cells that undergo terminal
      differentiation. Despite accumulation of senescence markers in aged skin,
      epidermal stem cells are maintained at normal levels throughout life. Therefore,
      skin ageing is induced by impaired stem cell mobilisation or reduced number of
      stem cells able to respond to proliferative signals. In the skin, existence of
      several distinct stem cell populations has been reported. Genetic labelling
      studies detected multipotent stem cells of the hair follicle bulge to support
      regeneration of hair follicles but not been responsible for maintaining
      interfollicular epidermis, which exhibits a distinct stem cell population. Hair
      follicle epithelial stem cells have at least a dual function: hair follicle
      remodelling in daily life and epidermal regeneration whenever skin integrity is
      severely compromised, e.g. after burns. Bulge cells, the first adult stem cells
      of the hair follicle been identified, are capable of forming hair follicles,
      interfollicular epidermis and sebaceous glands. In addition, -- at least in
      murine hair follicles -- they can also give rise to non-epithelial cells,
      indicating a lineage-independent pluripotent character. Multipotent cells (skin
      derived precursor cells) are present in human dermis; dermal stem cells represent
      0.3% among human dermal foreskin fibroblasts. A resident pool of progenitor cells
      exists within the sebaceous gland, which is able to differentiate into both
      sebocytes and interfollicular epidermis. The self-renewal and multi-lineage
      differentiation of skin stem cells make these cells attractive for ageing process
      studies but also for regenerative medicine, tissue repair, gene therapy and cell
      based therapy with autologous adult stem cells not only in dermatology. In
      addition, they provide in vitro models to study epidermal lineage selection and
      its role in the ageing process.

PMID- 18809488
TI  - Psychobiological responses to social threat: evolution of a psychological model
      in psychoneuroimmunology.
AB  - There exists a bidirectional network of interactions between the central nervous
      system, the endocrine system and the immune system. The existence of these
      pathways allows stressful life experience to impact the immune system with
      important implications for health. One powerful elicitor of changes in the
      autonomic, endocrine and immune systems is threat to social status. This review
      describes the development of a human model of social status threat that specifies
      a set of contextual, psychological and biological pathways that may underlie the
      health consequences of threats to social status and regard. The role of cognitive
      processes in shaping the physiological response to the social world will be
      emphasized.

PMID- 18809489
TI  - Reduction of oligodendrocyte myelin glycoprotein expression following facial
      nerve transection.
AB  - Oligodendrocyte myelin glycoprotein (OMgp) has been thought to be expressed in
      the oligodendrocytes and inhibit the regeneration of the nerves by binding to the
      Nogo receptor expressed in neurons in the central nervous system (CNS). However,
      OMgp is expressed in the CNS in the neurons as well as oligodendrocytes. In order
      to help understanding the physiological role of neuronal OMgp, we examined the
      change of OMgp expression in the facial nucleus after the facial nerve
      transection. Real-time RT-PCR and Western blot analysis showed a down-regulation
      of OMgp expression in the facial nucleus 5-7 (mRNA) or 5-14 (protein) days after
      transection. Thereafter, expression of OMgp returned to the control level at 28
      days after axotomy. Subsequent analysis using in situ hybridization
      histochemistry and immunohistochemistry established that the decrease of OMgp
      expression was attributable to the expression in facial motoneurons, but not in
      oligodendrocytes. These findings suggest a possibility that the change of
      neuronal OMgp expression might be involved in reconnection of neural circuit
      between axotomized facial neuron and upper motor neuron after transection.

PMID- 18809490
TI  - Mapping the gene expression universe.
AB  - Methods to globally survey gene expression provide valuable insights into gene
      function during development. In particular, comprehensive in situ hybridization
      studies have demonstrated that gene expression patterns are extraordinarily
      diverse and new imaging techniques have been introduced to capture these patterns
      with higher resolution at the tissue, cellular, and subcellular levels. The
      analysis of massive image databases can be greatly facilitated by computer vision
      techniques once annotated image sets reach the crucial mass sufficient to train
      the computer in pattern recognition. Ultimately, genome-wide atlases of gene
      expression during development will record gene activity in living animals with at
      least cellular resolution and in the context of morphogenetic events. These
      emerging datasets will lead to great advances in the field of comparative
      genomics and revolutionize our ability to decipher and model developmental
      processes for a variety of organisms.

PMID- 18809491
TI  - Central mechanisms of tactile shape perception.
AB  - Studies show that while the cortical mechanisms of two-dimensional (2D) form and
      motion processing are similar in touch and vision, the mechanisms of three
      dimensional (3D) shape processing are different. 2D form and motion are processed
      in areas 3b and 1 of SI cortex by neurons with receptive fields (RFs) composed of
      excitatory and inhibitory subregions. 3D shape is processed in area 2 and SII and
      relies on the integration of cutaneous and proprioceptive inputs. The RFs of SII
      neurons vary in size and shape with heterogeneous structures consisting of
      orientation-tuned fingerpads mixed with untuned excitatory or inhibitory
      fingerpads. Furthermore, the sensitivity of the neurons to cutaneous inputs
      changes with hand conformation. We hypothesize that these RFs are the kernels
      underlying tactile object recognition.

PMID- 18809492
TI  - Neural and behavioral mechanisms of olfactory perception.
AB  - Recent in vivo and in vitro studies have challenged existing models of olfactory
      processing in the vertebrate olfactory bulb and insect antennal lobe. Whereas
      lateral connectivity between olfactory glomeruli was previously thought to form a
      dense, topographically organized inhibitory surround, new evidence suggests that
      lateral connections may be sparse, nontopographic, and partly excitatory. Other
      recent studies highlight the role of active sensing (sniffing) in shaping odor
      evoked neural activity and perception.

PMID- 18809493
TI  - Probabilistic sensory recoding.
AB  - A hallmark of higher brain functions is the ability to contemplate the world
      rather than to respond reflexively to it. To do so, the nervous system makes use
      of a modular architecture in which sensory representations are dissociated from
      areas that control actions. This flexibility however necessitates a recoding
      scheme that would put sensory information to use in the control of behavior.
      Sensory recoding faces two important challenges. First, recoding must take into
      account the inherent variability of sensory responses. Second, it must be
      flexible enough to satisfy the requirements of different perceptual goals. Recent
      progress in theory, psychophysics, and neurophysiology indicate that cortical
      circuitry might meet these challenges by evaluating sensory signals
      probabilistically.

PMID- 18809495
TI  - Representation of binocular surfaces by cortical neurons.
AB  - Useful representations of the three-dimensional (3D) world go beyond assigning
      depth to individual points, building maps of surfaces and shapes. Studies in a
      wide range of extrastriate cortical areas have shown that single neurons show
      selective responses to 3D surfaces. The extent to which this advances the
      representation beyond that provided by the earliest binocular signals requires
      careful evaluation. We conclude that current data are not sufficient to identify
      distinctive contributions from different cortical areas to the binocular
      representation of 3D surfaces.

PMID- 18809494
TI  - Cochlear amplification, outer hair cells and prestin.
AB  - Mechanical amplification of acoustic signals is apparently a common feature of
      vertebrate auditory organs. In non-mammalian vertebrates amplification is
      produced by stereociliary processes, related to the mechanotransducer channel
      complex and probably to the phenomenon of fast adaptation. The extended frequency
      range of the mammalian cochlea has probably co-evolved with a novel hair cell
      type, the outer hair cell and its constituent membrane protein, prestin.
      Cylindrical outer hair cells are motile and their somatic length changes are
      voltage driven and powered by prestin. One of the central outstanding problems in
      mammalian cochlear neurobiology is the relation between the two amplification
      processes.

PMID- 18809496
TI  - Microbial recognition of human cell surface glycoconjugates.
AB  - Infection by pathogens is generally initiated by the specific recognition of host
      epithelia surfaces and subsequent adhesion is essential for invasion. In their
      infection strategy, microorganisms often use sugar-binding proteins, that is
      lectins and adhesins, to recognize and bind to host glycoconjugates where
      sialylated and fucosylated oligosaccharides are the major targets. The
      lectin/glycoconjugate interactions are characterized by their high specificity
      and most of the time by multivalency to generate higher affinity of binding.
      Recent crystal structures of viral, bacterial, and parasite receptors in complex
      with human histo-blood group epitopes or sialylated derivatives reveal new folds
      and novel sugar-binding modes. They illustrate the tight specificity between
      tissue glycosylation and lectins.

PMID- 18809497
TI  - Receptor binding and transactivation activities of red clover isoflavones and
      their metabolites.
AB  - Red clover extracts contain a variety of isoflavones, which have affinity toward
      estrogen receptor alpha (ERalpha), estrogen receptor beta (ERbeta), androgen
      receptor (AR), and progesterone receptor (PR). Upon ingestion, they undergo
      various metabolic transformations. For a complete evaluation of red clover
      extracts and possible health benefits, the resulting metabolites should also be
      investigated. Biochanin A, formononetin, genistein, daidzein, dihydrobiochanin A,
      dihydroformononetin, dihydrogenistein, dihydrodaidzein, 3'-hydroxygenistein, 6
      hydroxydaidzein, 6-hydroxydesmethylangolensin, equol, O-desmethylangolensin,
      angolensin, and p-ethylphenol were tested for their transactivation potential
      toward ERalpha, AR, and PR in yeast. Competitive binding assays with radiolabeled
      17beta-estradiol, 17alpha-methyltrienolone or progesterone assessed binding to
      the respective ERalpha and ERbeta, AR, and PR. The compounds showed only weak
      binding affinity to AR and PR, with IC(50) values being greater (i.e., lesser
      affinity) than 10(-5)M for the respective receptor. So far, beneficial health
      effects have been attributed to the production of equol. We propose that other
      metabolites can also contribute to these effects. However, more detailed
      information for the formation of these metabolites in humans and for
      bioavailability data are required to confirm our assumptions.

PMID- 18809498
TI  - Striosome-matrix pathology and motor deficits in the YAC128 mouse model of
      Huntington's disease.
AB  - Huntington's disease is characterized by striatal degeneration and progressive
      motor deficits. To examine striatal compartment-specific pathology and its
      relation to motor symptoms, we used immunohistochemistry to identify and measure
      the striosomes and matrix of 7-13-month-old YAC128 and wild type (WT) mice that
      were previously tested on motor tasks. Compared to WTs, 13-month-old YAC128s
      showed volume shrinkage in striosomes, and cell loss in both compartments. The
      percent cell loss was greater in striosomes than matrix. Striosome volume and
      cell loss was greatest in the dorsolateral striatum. YAC128 rotarod and balance
      beam deficits preceded volume and cell loss. At 13 months, YAC128 balance beam
      slips and striosome cell number were inversely correlated. The results show that
      pathology in older YAC128s manifests as an abnormal striosome to matrix ratio and
      suggest that this imbalance can contribute to some motor symptoms.

PMID- 18809499
TI  - High-level expression and purification of the second transmembrane domain of wild
      type and mutant human melanocortin-4 receptor for solid-state NMR structural
      studies.
AB  - It has been demonstrated that human melanocortin-4 receptor (hMC4R) plays an
      important role in the control of energy homeostasis, and heterozygous mutations
      in the hMC4R gene are the most frequent genetic cause of severe human obesity. In
      order to obtain additional insight into the structure and function, we cloned,
      expressed, and purified the second transmembrane domain of the wild-type hMC4R
      (wt-TM2) and D90N mutant hMC4R (m-TM2). To facilitate structural studies of these
      hMC4R by solid-state NMR, efficient methods for the production of milligram
      quantities of isotopically labeled protein are necessary. However, large-scale
      production of most transmembrane proteins has been limited by experimental
      adversities due to insufficient yields and low solubility of protein.
      Nevertheless, through the optimization of the expression and purification
      approach, we could obtain uniformly or selectively labeled fusion proteins in
      yields as high as 200-250 mg per liter M9 minimal medium. These proteins were
      overexpressed in inclusion bodies as a fusion protein with ketosteroid isomerase
      (KSI) in Escherichia coli, and the fusion protein was purified using immobilized
      metal affinity chromatography under denaturing conditions. wt-/m-TM2 peptides
      were released from the fusion by cyanogen bromide cleavage at the Met residue and
      separated from the carrier KSI by size exclusion chromatography. Initial
      structural data obtained by solution NMR measurements of wt-/m-TM2 is also
      presented. The successful application to the production of the second
      transmembrane domain of human MC4R indicates that the method can be applied to
      other transmembrane proteins as well and also enable its structural and
      functional studies using solid-state NMR spectroscopy.

PMID- 18809500
TI  - White matter damage impairs access to consciousness in multiple sclerosis.
AB  - Global neuronal workspace theory predicts that damage to long-distance white
      matter (WM) tracts should impair access to consciousness during the perception of
      brief stimuli. To address this issue, we studied visual backward masking in 18
      patients at the very first clinical stage of multiple sclerosis (MS), a
      neurological disease characterized by extensive WM damage, and in 18 matched
      healthy subjects. In our masking paradigm, the visibility of a digit stimulus
      increases non-linearly as a function of the interval duration between this target
      and a subsequent mask. In order to characterize quantitatively, for each subject,
      the transition between non-conscious and conscious perception of the stimulus, we
      used non-linear regression to fit a sigmoid curve to objective performance and
      subjective visibility reports as a function of target-mask delay. The delay
      corresponding to the inflexion point of the sigmoid, where visibility suddenly
      increases, was termed the "non-linear transition threshold" and used as a summary
      measure of masking efficiency. Objective and subjective non-linear transition
      thresholds were highly correlated across subjects in both groups, and were higher
      in patients compared to controls. In patients, variations in the non-linear
      transition threshold were inversely correlated to the Magnetization transfer
      ratio (MTR) values inside the right dorsolateral prefrontal WM, the right
      occipito-frontal fasciculus and the left cerebellum. This study provides clinical
      evidence of a relationship between impairments of conscious access and integrity
      of large WM bundles, particularly involving prefrontal cortex, as predicted by
      global neuronal workspace theory.

PMID- 18809501
TI  - Evidence for endogenous opioid release in the amygdala during positive emotion.
AB  - Endogenous opioid release has been linked to relief from aversive emotional
      memories, thereby promoting a euphoric state and subsequent interactions towards
      social stimuli resulting in the formation of social preferences. However, this
      theory remains controversial. Using positron emission tomography and
      [(11)C]diprenorphine (DPN) in healthy volunteers, we found significantly reduced
      DPN binding to opioid receptor in the hippocampus during positive mood induction
      compared to neutral mood. Furthermore, the magnitude of positive mood change
      correlated negatively with DPN binding in the amygdala bilaterally. Our finding
      of reduced DPN binding is consistent with increased release of endogenous
      opioids, providing direct evidence that localised release of endogenous opioids
      is involved in the regulation of positive emotion in humans.

PMID- 18809502
TI  - The Quadruple Process model approach to examining the neural underpinnings of
      prejudice.
AB  - In order to investigate the systems underlying the automatic and controlled
      processes that support social attitudes, we conducted an fMRI study that combined
      an implicit measure of race attitudes with the Quadruple Process model (Quad
      model). A number of previous neural investigations have adopted the Implicit
      Association Test (IAT) to examine the automatic processes that contribute to
      social attitudes. Application of the Quad model builds on this previous research
      by permitting measures of distinct automatic and controlled processes that
      contribute to performance on the IAT. The present research found that prejudiced
      attitudes of ingroup favoritism were associated with amygdala, medial and right
      lateral orbitofrontal cortex. In contrast, prejudiced attitudes of outgroup
      negativity were associated with caudate and left lateral orbitofrontal cortex.
      Frontal regions found in previous neural research on the IAT, such as anterior
      cingulate, dorsolateral prefrontal cortex and operculum were associated with
      detecting appropriate responses in situations in which they conflict with
      automatic associations. Insula activity was associated with attitudes towards
      ingroup and outgroup members, as well as detecting appropriate behavior.

PMID- 18809503
TI  - A multiplex primer extension assay for the rapid identification of paternal
      lineages in domestic goat (Capra hircus): Laying the foundations for a detailed
      caprine Y chromosome phylogeny.

PMID- 18809504
TI  - Molecular systematics and phylogeography of the gigantic earthworms of the
      Metaphire formosae species group (Clitellata, Megascolecidae).
AB  - The earthworms of the Metaphire formosae species group distributed in Taiwan are
      members of the Pheretima complex within the Megascolecidae. In this study, the
      systematics and phylogeography of this species group were investigated using DNA
      sequences of mitochondrial cytochrome c oxidase subunit I (COI), 16S ribosomal
      (r)RNA, and NADH dehydrogenase subunit 1 (ND1). The results indicated that the 13
      taxa of the M. formosae species group form a clade, including a cryptic species
      discovered in this study. In addition, Metaphire hengchunensis (James, S.W.,
      Shih, H.-T., Chang, H.-W., 2005. Seven new species of Amynthas (Clitellata:
      Megascolecidae) and new earthworm records from Taiwan. J. Nat. Hist. 39, 1007
      1028) should be regarded as a subspecies of Metaphire paiwanna Tsai, C.-F., Shen,
      H.-P., Tsai, S.-C., 2000a. Native and exotic species of terrestrial earthworm
      (Oligochaeta) in Taiwan with reference to Northeast Asia. Zool. Stud. 39, 285
      294, Tsai, C.-F., Tsai, S.-C., Liaw, G.-J., 2000b. Two new species of pontandric
      pheretimoid earthworms belonging to the genus Metaphire (Megascolecidae:
      Oligochaeta) from Taiwan. J. Nat. Hist. 34, 1731-1741, and Metaphire bununa
      glareosa Tsai et al. 2000 should be elevated to specific status.
      Phylogeographical inferences showed that allopatric speciation occurred in this
      species group during the rapid uplift of the main island of Taiwan between 5.0
      and 2.5 million years ago. Our analysis exposes non-monophyly within each of the
      genera Amynthas and Metaphire, and more generally within the Pheretima complex.
      Further revisions of this speciose complex are urgently needed.

PMID- 18809506
TI  - Toll-like receptor (TLR2, TLR4 and TLR5) gene polymorphisms and Helicobacter
      pylori infection in children with and without duodenal ulcer.
AB  - Helicobacter pylori infection is mainly acquired in childhood, and polymorphisms
      in the host genes coding for Toll-like receptors (TLRs) may influence the innate
      and adaptive immune response to the infection, affecting the susceptibility to H.
      pylori or the disease outcomes. Our aim was to investigate whether TLR4, TLR2,
      and TLR5 polymorphisms were associated with H. pylori susceptibility and risk for
      duodenal ulcer in children. Gastric biopsy specimens were obtained at endoscopy
      for evaluation of H. pylori status, TLR4, TLR2 and TLR5 polymorphisms from 486
      children (254 H. pylori-negative and 232 H. pylori-positive: 72 with and 160
      without duodenal ulcer). cagA status of H. pylori infection was investigated by
      PCR. The levels of gastric cytokines were detected by ELISA. H. pylori-positivity
      or duodenal ulcer were not associated with TLR2, TLR4 or TLR5 polymorphisms.
      Otherwise, the presence of TLR4 polymorphic allele was associated with infection
      by cagA-positive strains and with increased gastric levels of interleukin-8 and
      interleukin-10. TLR4 polymorphism might ultimately contribute to more severe
      consequences of the infection in adulthood since it was associated with
      susceptibility to cagA-positive H. pylori infection early in life.

PMID- 18809505
TI  - Neurotransmitter release during delay eyeblink classical conditioning: role of
      norepinephrine in consolidation and effect of age.
AB  - Delay classical eyeblink conditioning (EBC) is an important model of associative,
      cerebellar-dependent learning. Norepinephrine (NE) plays a significant modulatory
      role in the acquisition of learning; however, other neurotransmitters are also
      involved. The goal was to determine whether NE, gamma-aminobutyric acid (GABA)
      and glutamate (GLU) release are observed in cerebellar cortex during EBC, and
      whether such release was selectively associated with training. Further studies
      examined the role of the beta-noradrenergic receptor in consolidation of the
      learned response by local infusion of propranolol at 5-120 min following training
      into the cerebellar cortex. In vivo microdialysis coupled to EBC was performed to
      examine neurotransmitter release. An increase in the extracellular level of NE
      was observed during EBC and was maximal on day 1 and diminished in amplitude with
      subsequent days of training. No changes in baseline NE release were observed in
      pseudoconditioning indicating that NE release is directly related to the
      associative learning process. The extracellular levels of GABA were also
      increased selectively during paired training however, the magnitude of GABA
      release increased over days of training. GLU release was observed to increase
      during both paired and unpaired training, suggesting that learning does not occur
      prior to the information arriving in the cerebellum. When propranolol was
      administered at either 5-, 60-, or 120-min post-training, there was an inhibition
      of conditioned responses, these data support the hypothesis that NE is important
      for consolidation of learning. In another set of experiments we demonstrate that
      the timing of release of NE, GABA and glutamate are significantly delayed in
      onset and lengthened in duration in the 22-month-old F344 rats. Over days of
      training the timing of release becomes closer to the timing of training and this
      is associated with increased learning of conditioned responses in the aged rats.

PMID- 18809507
TI  - Darwin's concepts in a test tube: parallels between organismal and in vitro
      evolution.
AB  - The evolutionary process as imagined by Darwin 150 years ago is evident not only
      in nature but also in the manner in which naked nucleic acids and proteins
      experience the "survival of the fittest" in the test tube during in vitro
      evolution. This review highlights some of the most apparent evolutionary
      patterns, such as directional selection, purifying selection, disruptive
      selection, and iterative evolution (recurrence), and draws parallels between what
      happens in the wild with whole organisms and what happens in the lab with
      molecules. Advances in molecular selection techniques, particularly with
      catalytic RNAs and DNAs, have accelerated in the last 20 years to the point where
      soon any sort of complex differential hereditary event that one can ascribe to
      natural populations will be observable in molecular populations, and exploitation
      of these events can even lead to practical applications in some cases.

PMID- 18809508
TI  - Super-resolution microscopy by nanoscale localization of photo-switchable
      fluorescent probes.
AB  - A new form of super-resolution fluorescence microscopy has emerged in recent
      years, based on the high accuracy localization of individual photo-switchable
      fluorescent labels. Image resolution as high as 20 nm in the lateral dimensions
      and 50 nm in the axial direction has been attained with this concept,
      representing an order of magnitude improvement over the diffraction limit. The
      demonstration of multicolor imaging with molecular specificity, three-dimensional
      (3D) imaging of cellular structures, and time-resolved imaging of living cells
      further illustrates the exciting potential of this method for biological imaging
      at the nanoscopic scale.

PMID- 18809509
TI  - Visual acuity and sensitivity increase allometrically with body size in
      butterflies.
AB  - In insects, the surface area of the compound eye increases with body size both
      within and between species with only a slight negative allometry. This increase
      in surface area permits changes in eye structure that affect the eye's acuity and
      sensitivity, two features of eye performance that cannot be simultaneously
      maximized. Hence, as eye size varies within a lineage, so will the compromises
      between features that maximize acuity and those that maximize sensitivity. We
      examined these compromises in four species of nymphalid butterflies that varied
      in body mass over almost two orders of magnitude. The largest of these species
      was crepuscular and so additionally may indicate the potential effect of life
      style on eye structure. Across these species, as body size increased, facet
      diameters increased while interommatidial angles decreased. Finally, the eye
      parameter was fairly constant across species except in the crepuscular species in
      which some notably large values were observed in the frontal visual field. Based
      on our measurements, large butterflies have more acute and more sensitive vision
      than smaller butterflies. However, full understanding of the behavioral
      implications of this relationship awaits information on the temporal resolution
      of their eyes because typical flight velocities also increase with body size.

PMID- 18809510
TI  - Antennal pathways in the central nervous system of a blood-sucking bug, Rhodnius
      prolixus.
AB  - The haematophagous bug Rhodnius prolixus has been a model system in insect
      physiology for a long time. Recently, several studies have been devoted to its
      sensory systems, including olfaction. However, few data are available on the
      basic organisation of the nervous system in this species. By means of neuronal
      backfills, histology, confocal microscopy and three-dimensional reconstruction
      methods, we have characterized the projection patterns of antennal sensory
      neurons within the central nervous system of this disease-vector insect. We
      established the first partial three-dimensional map of the antennal lobe (AL) of
      a hemipteran insect. The ALs of this species are relatively diffuse structures,
      which nevertheless show a glomerular organisation. Based on computer
      reconstruction of the AL, 22 glomeruli with a radius of 8-25 microm could be
      identified. No obvious sexual dimorphism of the glomerular architecture was
      observed. Antennal afferents project not only into the deutocerebrum, but also
      some fibres descend through the ventral nerve cord to ganglia belonging to the
      abdominal segments.

PMID- 18809511
TI  - Analysis of dynamics and propagation of parietal cingulate seizures with
      secondary mesial temporal involvement.
AB  - Cingulate-onset seizures, particularly those originating from parietal cingulate
      regions, are inadequately described and confounded by patterns of propagation. We
      analyzed scalp and depth electrode recordings in a patient whose seizures
      originated from a lesion in the right posterior cingulate region and produced
      secondary seizure activity in ipsilateral mesial temporal structures. Analyses
      included the matching pursuit (MP) method of time-frequency decomposition and the
      Gabor atom density (GAD) measure of signal complexity. Although scalp recordings
      suggested a right temporal onset, seizures recorded with depth electrodes clearly
      began in the parietal cingulate region before producing a secondary discharge in
      ipsilateral mesial structures. GAD revealed a significant increase in complexity
      during ictal cingulate activity and a consistent pattern of subsequent complexity
      changes in the hippocampus 30 seconds later. MP and GAD measures were valuable
      supplements to confirm the stereotyped pattern of both time-frequency changes and
      complexity. This provides additional evidence for pathways between the parietal
      cingulate region and mesial temporal structures and raises questions as to
      whether parietal cingulate seizures can produce clinical symptoms independent of
      regional or remote propagation.

PMID- 18809512
TI  - Does the decision in a validation process of a surrogate endpoint change with
      level of significance of treatment effect? A proposal on validation of surrogate
      endpoints.
AB  - BACKGROUND: In recent years the use of surrogate end points (S) has become an
      interesting issue. In clinical trials, it is important to get treatment outcomes
      as early as possible. For this reason there is a need for surrogate endpoints (S)
      which are measured earlier than the true endpoint (T). However, before a
      surrogate endpoint can be used it must be validated. For a candidate surrogate
      endpoint, for example time to recurrence, the validation result may change
      dramatically between clinical trials. The aim of this study is to show how the
      validation criterion (R(2)(trial)) proposed by Buyse et al. are influenced by the
      magnitude of treatment effect with an application using real data. METHODS: The
      criterion R(2)(trial) proposed by Buyse et al. (2000) is applied to the four data
      sets from colon cancer clinical trials (C-01, C-02, C-03 and C-04). Each clinical
      trial is analyzed separately for treatment effect on survival (true endpoint) and
      recurrence free survival (surrogate endpoint) and this analysis is done also for
      each center in each trial. Results are used for standard validation analysis. The
      centers were grouped by the Wald statistic in 3 equal groups. RESULTS: Validation
      criteria R(2)(trial) were 0.641 95% CI (0.432-0.782), 0.223 95% CI (0.008-0.503),
      0.761 95% CI (0.550-0.872) and 0.560 95% CI (0.404-0.687) for C-01, C-02, C-03
      and C-04 respectively. The R(2)(trial) criteria changed by the Wald statistics
      observed for the centers used in the validation process. Higher the Wald
      statistic groups are higher the R(2)(trial) values observed. CONCLUSION: The
      recurrence free survival is not a good surrogate for overall survival in clinical
      trials with non significant treatment effects and moderate for significant
      treatment effects. This shows that the level of significance of treatment effect
      should be taken into account in validation process of surrogate endpoints.

PMID- 18809513
TI  - Urinary evaluation of the balance between soluble interferon-gamma receptor (IFN
      gammaR1) and interleukin-4 receptor (IL-4Ralpha).
AB  - To elucidate the usefulness of the simultaneous analysis of multiple kinds of
      soluble cytokine receptors in urine specimens, we determined the levels of both
      the soluble interferon-gamma receptor alpha chain (sIFN-gammaR1, Th1-type
      cytokine receptor) and the soluble interleukin 4-receptor alpha chain (sIL
      4Ralpha, Th2-type cytokine receptor) in the urine of healthy subjects as
      reference values and preliminarily applied this method to evaluate patients with
      diarrhea positive (D+) hemolytic uremic syndrome (HUS) as the diagnostic
      parameters. The urinary sIFN-gammaR levels of children were significantly lower
      than those of adults (p < 0.01, n = 107). On the other hand, there was no
      significant difference between the urine sIL-4R levels of adults and children.
      Statistical correlation between sIFN-gammaR and sIL-4R values was not observed (p
      = 0.705). On the day of onset of HUS, the urine sIFN-gammaR levels of the
      patients (n = 6) with HUS were higher than those of the healthy control group (n
      = 67) (p < 0.01); however, there was no significant difference in the sIL-4R
      levels between both groups. The urine evaluation of the balance between the
      soluble cytokine receptors might be informative for the immune states of HUS
      patients.

PMID- 18809514
TI  - Functional analyses for tRNase Z variants: an aspartate and a histidine in the
      active site are essential for the catalytic activity.
AB  - We performed functional analyses for various single amino-acid substitution
      variants of Escherichia coli, Bacillus subtilis, and human tRNase Zs. The well
      conserved six histidine, His(I)-His(VI), and two aspartate, Asp(I) and Asp(II),
      residues together with metal ions are thought to form the active site of tRNase
      Z. The Mn(2+)-rescue analysis for Thermotoga maritima tRNase Z(S) has suggested
      that Asp(I) and His(V) directly contribute the proton transfer for the catalysis,
      and a catalytic mechanism has been proposed. However, experimental evidence
      supporting the proposed mechanism was limited. Here we intensively examined E.
      coli and B. subtilis tRNase Z(S) variants and human tRNase Z(L) variants for
      cleavage activities on pre-tRNAs in the presence of Mg(2+) or Mn(2+) ions. We
      observed that the Mn(2+) ions cannot rescue the activities of Asp(I)Ala and
      His(V)Ala variants from each species, which are lost in the presence of Mg(2+).
      This observation may support the proposed catalytic mechanism.

PMID- 18809515
TI  - The conserved Cys254 plays a crucial role in creatine kinase refolding under non
      reduced conditions but not in its activity or stability.
AB  - Oxidative stress is a common factor that may affect cell survival in extreme or
      disease-related conditions, and it is important for the cells to develop not only
      redox homeostatic mechanisms, but also adequate protein-protecting mechanisms to
      fight against oxidative stress. In this research, we investigated the role of the
      conserved C254 in the refolding of creatine kinase (CK), a key cytosolic enzyme
      involved in intracellular energetics. It was found that the conserved C254 did
      not contribute to the activity, structure, stability and unfolding of CK, but
      played a crucial role in CK refolding under non-reduced conditions by preventing
      off-pathway aggregation. This property of C254 might be a result of natural
      selection of CK to fight against oxidative stresses that are frequently
      encountered by vertebrate cells. The results herein not only confirmed that the
      reduced condition is important to the activity, structural stability and folding
      of cytosolic proteins, but also highlighted that it is also crucial for cytosolic
      proteins to maintain the ability to fold correctly under non-reduced conditions.

PMID- 18809516
TI  - Modulation of adipogenesis-related gene expression by estrogen-related receptor
      gamma during adipocytic differentiation.
AB  - Estrogen-related receptor gamma (ERRgamma) is an orphan nuclear receptor that
      regulates cellular energy metabolism by modulating gene expression involved in
      oxidative metabolism and mitochondrial biogenesis in brown adipose tissue and
      heart. However, the physiological role of ERRgamma in adipogenesis and the
      development of white adipose tissue has not been well studied. Here we show that
      ERRgamma was up-regulated in murine mesenchyme-derived cells, especially in ST2
      and C3H10T1/2 cells, at mRNA levels under the adipogenic differentiation
      condition including the inducer of cAMP, glucocorticoid, and insulin. The up
      regulation of ERRgamma mRNA was also observed in inguinal white adipose and brown
      adipose tissues of mice fed a high-fat diet. Gene knockdown by ERRgamma-specific
      siRNA results in mRNA down-regulation of adipogenic marker genes including fatty
      acid binding protein 4, PPARgamma, and PGC-1beta in a preadipocyte cell line 3T3
      L1 preadipocytes and mesenchymal ST2 and C3H10T1/2 cells in the adipogenesis
      medium. In contrast, stable expression of ERRgamma in 3T3-L1 cells resulted in up
      regulation of these adipogenic marker genes under the adipogenic condition. These
      results suggest that ERRgamma positively regulate the adipocyte differentiation
      with modulating the expression of various adipogenesis-related genes.

PMID- 18809518
TI  - Broadening the dimensions of anesthesia.

PMID- 18809519
TI  - Comparison of three different concentrations of ropivacaine for postoperative
      patient-controlled thoracic epidural analgesia after upper abdominal surgery.
AB  - BACKGROUND: Previous studies have reported the comparable efficacy of
      ropivacaine/fentanyl for patient-controlled epidural analgesia (PCEA). In our
      hospital, three different concentrations of ropivacaine solution (0.1%, 0.15%,
      0.2%) in combination with 1 microg/mL fentanyl were available for PCEA. As some
      studies have reported a much higher incidence of motor block and opioid-related
      side effects with 0.2% ropivacaine in combination with 4 microg/mL fentanyl, it
      was our intent to analyze the data of our patients who had received PCEA after
      upper abdominal surgery. In addition to comparing the analgesic effects and the
      incidence of motor block and opioid-related side effects of these three different
      ropivacaine/fentanyl solutions, we also evaluated the workload of our pain staff.
      The main purpose of our study was to determine which of these three regimens of
      ropivacaine was most satisfactory with the least workload for the pain service
      staff. METHODS: In total, 33 patients who had received PCEA after upper abdominal
      surgery were included in the analysis. The number of patients in each
      ropivacaine/fentanyl group was 11 (group 1, 0.1% ropivacaine; group 2, 0.15%;
      group 3, 0.2%). The PCEA device was programmed to deliver a patient-controlled
      bolus of 2 mL with a lockout time of 20 minutes and background infusion of 5
      mL/hr for 72 hours. Visual analog scale (VAS) pain scores, adverse events and the
      extent of sensory or motor block were recorded 12, 36 and 60 hours after surgery.
      The total volume of analgesic solution consumed and the frequency of requisite
      attendance by pain service staff were also recorded. RESULTS: There were no
      differences among the three groups regarding total consumption. In group 1, VAS
      scores during ambulation and cough 12 hours postoperatively were significantly
      higher than in the other two groups (p < 0.05). There was no motor block. Four
      patients in group 3 suffered from loss of temperature sensation. The overall
      incidence of adverse events was less than 40%. CONCLUSION: Both thoracic epidural
      0.15% and 0.2% ropivacaine provide effective postoperative pain control in
      combination with fentanyl without motor block. A 0.15% ropivacaine-1 microg/mL
      fentanyl solution is preferable considering the lower incidence of adverse
      events.

PMID- 18809517
TI  - Nuclear factor I transcription factors regulate IGF binding protein 5 gene
      transcription in human osteoblasts.
AB  - Insulin-like growth factor binding protein 5 (IGFBP5) is expressed in many cell
      types including osteoblasts and modulates IGF activities. IGFBP5 may affect
      osteoblasts and bone formation, in part by mechanisms independent of binding
      IGFs. The highly conserved IGFBP5 proximal promoter within 100 nucleotides of the
      start of transcription contains functional cis regulatory elements for C/EBP, Myb
      and AP-2. We report evidence for a functional Nuclear Factor I (NFI) cis element
      that mediates activation or repression of IGFBP5 transcription by the NFI gene
      family. All four NFI genes were expressed in human osteoblast cultures and
      osteosarcoma cell lines. Co-transfection with human IGFBP5 promoter luciferase
      reporter and murine Nfi expression vectors showed that Nfib was the most active
      in stimulating transcription. Nfix was less active and Nfia and Nfic were
      inhibitory. Knockdown of NFIB and NFIC expression using siRNA decreased and
      increased IGFBP5 expression, respectively. Analysis of IGFBP5 promoter deletion
      and mutation reporter constructs identified a functional NFI cis element. All
      four NFI proteins bound the NFI site in electrophoretic mobility shift
      experiments and NFIB bound in chromatin immunoprecipitation assays. Results
      suggest that NFI proteins are important regulators of IGFBP5 expression in human
      osteoblasts and thus in modulating IGFBP5 functions in bone.

PMID- 18809520
TI  - Use of spectral entropy monitoring in reducing the quantity of sevoflurane as
      sole inhalational anesthetic and in decreasing the need for antihypertensive
      drugs in total knee replacement surgery.
AB  - BACKGROUND: The use of spectral entropy for monitoring the depth of anesthesia or
      level of hypnosis in surgery or painful procedures can reduce the consumption of
      drugs and shorten the recovery time of total intravenous anesthesia such as by
      propofol. The aim of this study was to investigate: (1) the consumption of
      sevoflurane as the sole anesthetic; and (2) hemodynamic stability in orthopedic
      surgery with tourniquet inflation under the guidance of spectral entropy, in
      contrast with the conventional method. METHODS: Sixty-five patients, ASA I or II,
      scheduled to undergo total knee replacement were enrolled and randomized into an
      entropy-guided group or a conventionally-monitored group. In the conventional
      group, the depth of anesthesia was judged by the clinical experience of the
      anesthesia provider based on the hemodynamic response. In the entropy group,
      state entropy (SE) and response entropy (RE) were kept within the range of 35-45
      and an adequate gradient of 5-10 intraoperatively. The overall consumption of
      sevoflurane (mL) was monitored by the GE Datex-Ohemda S/5 Anesthetic Delivery
      Unit System. The physiologic changes during five major events in sequence in
      total knee replacement surgery, i.e., intubation, tourniquet inflation, skin
      incision, deflation and extubation, were observed closely over the first 5
      minutes after each individual event. Within the first 5 minutes of each event,
      antihypertensive drugs were prohibited. The rest of the time, changes were
      recorded at 5-minute intervals and the use of rescue medication was allowed in
      case of need. We compared the heart rate, mean arterial pressure, SE, RE,
      sevoflurane concentration and rescue drugs in both groups. RESULTS: The
      sevoflurane consumption was significantly lower in the entropy group than in the
      conventional group (27.79 +/- 7.4 mL vs. 31.42 +/- 6.9 mL; p < 0.05). During the
      first 5 minutes of each major event, there were no significant differences in
      hemodynamics between the two groups. In the ensuing time, entropy-guided
      anesthesia was associated with significantly less frequent need of
      antihypertensive drugs (0.94 vs. 1.48 times; p = 0.043), especially in the 45-60
      minutes after tourniquet inflation (p = 0.012). CONCLUSION: Using spectral
      entropy monitoring for guiding the depth of sevoflurane anesthesia in total knee
      replacement surgery can reduce its consumption and the frequency of use of
      antihypertensive drugs.

PMID- 18809521
TI  - The relationship between lockout interval and requirement for patient-controlled
      epidural analgesia.
AB  - BACKGROUND: Patient-controlled epidural analgesia (PCEA) with background infusion
      provides better analgesia than the use of a demand dose alone but might be
      associated with more consumption of PCEA solution and adverse effects. Therefore,
      we conducted this retrospective study to evaluate the influence of parameters of
      the drug delivery system on the PCEA requirements of patients receiving thoracic
      or upper abdominal surgeries. METHODS: Patients having operations involving the
      chest or upper abdomen with postoperative PCEA were included in the analyses. A
      standardized analgesic solution of bupivacaine (0.0625%) and fentanyl (1
      microg/mL) was used for all patients. The cumulative doses of PCEA on the first,
      second and third postoperative days were recorded. Collected data included
      patient demographics and their quantity of PCEA. A general linear model was used
      to compare within-subject time effects and between-subject effects. Interactions
      with time between subjects were also examined. RESULTS: A total of 228 patients
      (68 females, 160 males) were included in the study. The PCEA requirements
      decreased gradually over time (p < 0.001). Patients with lower body mass index
      had a greater difference in their PCEA requirement between the first and second
      postoperative days (p < 0.001). For variables related to PCEA usage, patients
      using PCEA with the 30-minute lockout interval used less PCEA infusate per day (p
      = 0.04 for main effect, p = 0.02 for interaction with time). Moreover, a longer
      lockout interval was not associated with poorer analgesic effects (p = 0.48).
      Other parameters had no significant influence on daily PCEA requirements.
      CONCLUSION: Patients receiving PCEA with a 30-minute lockout and background
      infusion used the least amount of PCEA infusate and the differences increased
      over time. Further investigations are recommended to evaluate potential benefits
      and drawbacks of a longer lockout interval.

PMID- 18809522
TI  - Clonidine enhances type-2 cationic amino acid transporter transcription in
      endotoxin-activated murine macrophages.
AB  - BACKGROUND: We sought to evaluate the effects of clonidine on type-2 cationic
      amino acid transporter (CAT-2) transcription in endotoxin-activated murine
      macrophages. METHODS: To determine the effects of clonidine on CAT-2
      transcription, confluent murine macrophages (RAW264.7 cells) were treated with 1x
      phosphate buffered saline, clonidine (1000 microM), lipopolysaccharide (LPS, 100
      ng/mL), or LPS plus clonidine (10, 100, or 1000 microM). After reacting with LPS
      for 18 hours or a comparable duration in groups without LPS, cell cultures were
      harvested and the CAT-2 mRNA concentration was assayed. To determine the
      stability of CAT-2 mRNA, confluent macrophages were treated with LPS or LPS plus
      clonidine (100 microM). After reacting with LPS for 6 hours, CAT-2 transcription
      was terminated and the stability of CAT-2 mRNA was determined. RESULTS: The CAT-2
      mRNA concentration of cell cultures receiving LPS plus clonidine (100 microM) or
      LPS plus clonidine (1000 microM) were significantly higher than that of the cell
      cultures receiving LPS alone, whereas the CAT-2 mRNA concentrations of cell
      cultures receiving LPS plus clonidine (10 microM) was comparable to that of cell
      cultures receiving LPS alone. The data indicated that clonidine significantly
      enhanced LPS-induced CAT-2 transcription. The estimated half-life of CAT-2 mRNA
      of cell cultures receiving LPS was similar to that of cell cultures receiving LPS
      plus clonidine. These results indicated that clonidine did not affect CAT-2 mRNA
      stability. CONCLUSION: Clonidine enhances CAT-2 transcription in endotoxin
      activated murine macrophages.

PMID- 18809523
TI  - Severe carbon dioxide retention during second laparoscopic surgery for urgent
      repair of an operative defect from the preceding laparoscopic surgery.
AB  - A 61-year-old male patient underwent laparoscopic cholecystectomy on diagnosis of
      acute cholecystitis. Thirteen hours later, bile leakage was noted and a second
      laparoscopic surgery was performed to rectify this. Severe hypercapnia and acute
      respiratory acidosis occurred during the act of CO2 pneumoperitoneum. The
      accumulated CO2 could not be eliminated effectively in spite of deliberate
      adjustment of the respiratory parameters. We suspected that abnormally high CO2
      absorption, which outweighed the capability of physiologic elimination in the
      presence of acute peritonitis, was the cause of the severe CO2 retention in the
      second laparoscopic surgery. The patient remained intubated with mechanical
      ventilatory support after surgery. Excessive internal CO2 was washed out
      gradually and the patient was extubated successfully the next morning. Profound
      inflammatory responses in peritonitis may increase permeability and absorption of
      CO2. Hypercapnia can occur as the store of CO2 in the tissues is saturated and
      there is continuous inflow of external CO2. It usually takes several hours to
      achieve a steady state of CO2 elimination after desufflation of CO2
      pneumoperitoneum and mechanical ventilatory support may sometimes be needed. In
      conclusion, caution should be taken against hypercapnia and respiratory acidosis
      in patients with peritonitis undergoing laparoscopic surgery because of the
      likelihood of these events occurring during the procedure.

PMID- 18809524
TI  - Spontaneous intracranial hypotension treated by epidural blood patches.
AB  - We present a case of spontaneous intracranial hypotension (SIH) diagnosed from
      the clinical symptoms and magnetic resonance imaging brain scans. After failure
      of conservative treatment, and lack of identification of the cerebrospinal fluid
      leak site, the headache was managed successfully and simply with two applications
      of an epidural blood patch (EBP). The strategy of our management for the patient
      was as follows: (1) application of an EBP to the lumbar epidural space initially
      and manipulating it into the proximity of the possible leak site; (2) a greater
      volume of autologous blood was injected at the second attempt of EBP; and (3) the
      patient was required to lie flat for at least 2 hours after the procedure. Better
      management of SIH is still developing. Traditionally, SIH is initially managed by
      conservative treatment. However, recent studies have shown that the success rate
      in arresting SIH after weeks or months of conservative treatment is not quite
      satisfactory. Hence, the EBP has proven to be more effective in treating SIH
      patients. Early EBP application may offer immediate relief of clinical symptoms.
      The role of the EBP in treating SIH patients should have greater emphasis and its
      application is worth recommendation.

PMID- 18809525
TI  - Upper airway obstruction after cervical spine fusion surgery: role of cervical
      fixation angle.
AB  - Upper airway obstruction is one of the life-threatening events in cervical spine
      surgery. The risk is particularly great during the period immediately after
      operation. We present the case of a 56-year-old female with breast cancer and
      metastasis to the cervical spine. The surgical procedure involved C2-C3
      laminectomy, posterior fixation (C0-C5), and C2 neurectomy. Tracheal extubation
      was carried out in the intensive care unit, and upper airway obstruction
      immediately followed. Emergency cricothyrotomy was performed under well-managed
      ventilation with a laryngeal mask after several failed intubation attempts. Over
      flexion of the cervical spine fixation and severe prevertebral soft tissue
      swelling were the most probable causes of upper airway obstruction. With a well
      adjusted angle for fixation of the cervical spine under fluoroscopic guidance
      before the procedure, such a surgical mishap could be avoided. Reintubation with
      a fiberscope might be considered first, and sustaining intubation for 2-3 days
      postoperatively could be safer in such high risk patients.

PMID- 18809526
TI  - Acute myocarditis-related complete atrioventricular block---an accidental finding
      in an acute appendicitis patient.
AB  - We report a 20-year-old male patient with preoperatively undiagnosed myocarditis,
      who received general anesthesia for laparoscopic appendectomy. Because of
      arrhythmia, a cardiologist was consulted postoperatively. The 12-lead
      electrocardiogram showed complete atrioventricular block and the echocardiogram
      showed global hypokinesia of the left ventricle with impaired contractility, a
      left ejection fraction of 37%, and a dilated right heart. Subsequently, a
      permanent pacemaker was implanted and the patient was discharged from hospital
      without any complications.

PMID- 18809527
TI  - Aphonia and quadriplegia---a rare complication following epidural labor
      analgesia.
AB  - We report an obstetric patient who developed unusual neurological complications
      after an epidural injection of a local anesthetic and a narcotic in a seemingly
      faultless manner. Ten minutes after receiving a loading dose, the patient
      developed aphonia, quadriplegia, and facial palsy while retaining normal
      consciousness and stable hemodynamics. The episode spontaneously resolved 40
      minutes later. We wish to draw attention to anesthesiologists of the possibility
      that even in the presence of a negative aspiration test or without noticeable
      dural puncture, the injected drugs may enter the intrathecal or subdural space
      instead of pooling entirely in the epidural compartment. Once an unexpected high
      block and unusual symptoms or signs are noted, a prompt differential diagnosis
      must be made and treatment initiated as soon as possible.

PMID- 18809528
TI  - Another drug ampoule mishap---regional problem and global concern.

PMID- 18809529
TI  - Risk factors for suicide in Taiwanese college students.
AB  - OBJECTIVE: The authors investigated the personality characteristics,
      psychopathology, parenting style, and family function among Taiwanese college
      students with high, moderate, and low suicidal risks. PARTICIPANTS: The sample
      included 2,919 first-year college students (1,414 men, 1,505 women) from a
      university in Taipei, Taiwan. METHODS: A self-administered questionnaire assessed
      domains covering demographics, personality, psychopathology, frequency of
      substance use, parenting style, family functioning, and suicidal behaviors. The
      authors used mixed models for data analysis. RESULTS: The authors observed a
      positive linear trend between increased suicidal tendency and levels of
      neuroticism, harm avoidance, novelty seeking, psychopathology, and parenting
      styles of low affection, overprotection, and authoritarian controlling. Use of
      tobacco and alcohol and impaired family adaptation and cohesion were associated
      with high and moderate suicidal risks. CONCLUSIONS: Personality, psychopathology,
      substance use, and familial factors are important correlates of suicidal risks
      among college students in Taiwan. Optimal suicide prevention strategies in the
      college setting should incorporate the multiple facets of suicidal risks.

PMID- 18809530
TI  - Sex and cultural differences in the acceptance of functional foods: a comparison
      of American, Canadian, and French college students.
AB  - OBJECTIVE: Functional foods (FF)--foods containing nutritional supplements in
      addition to natural nutrients--have an increasing presence in the marketplace.
      Expanding on previous research, the authors investigated college students'
      acceptance of FF. PARTICIPANTS: In September--March 2004, 811 undergraduates in
      Canada, the United States, and France participated in the study. METHODS: A self
      administered questionnaire measured students' general food attitudes and beliefs
      as well as FF-related knowledge, attitudes, beliefs, and purchase intention.
      RESULTS: Overall, participants slightly favored FF over traditional foods.
      However, although most respondents associated FF with positive health benefits,
      many remained dubious of currently available FF information. In terms of culture
      and sex, the authors found small but significant divergences in FF knowledge,
      attitudes, and behaviors. CONCLUSIONS: Stronger labeling and education efforts
      may increase cross-cultural acceptance of FF by college students.

PMID- 18809531
TI  - Sleep and behavioral correlates of napping among young adults: a survey of first
      year university students in Madrid, Spain.
AB  - OBJECTIVE: Between November 2002 and March 2003, the authors assessed the
      prevalence and correlates of napping among Spanish university students.
      PARTICIPANTS: The sample comprised 1,276 first-year university students; the mean
      age was 18.74 +/- 1.24 years, and 35.45% were men. METHODS: The study was cross
      sectional, and the students completed self-report, anonymous questionnaires
      provided during an in-class survey. RESULTS: Almost half (44%) of the sample
      reported napping (90% did so after lunch for longer than 1 hour). Multiple
      logistic regression analysis showed that experiencing an irregular sleep
      wakefulness pattern, having a morning school schedule, and being male were
      significant predictor variables of napping. Further significant outcome variables
      related to napping were having excessive daytime sleepiness, missing classes
      because of tiredness, better ability to concentrate later in the afternoon, and a
      perception of deeper nighttime sleep. CONCLUSIONS: Habitual napping is common
      among Spanish university students and associated with an irregular sleep
      wakefulness pattern. Taking long postlunch naps seems to be used by students to
      cope with insufficient sleep and daytime sleepiness.

PMID- 18809532
TI  - Increasing walking in college students using a pedometer intervention:
      differences according to body mass index.
AB  - OBJECTIVE: The researchers assessed the effectiveness of a pedometer intervention
      and differences in walking behaviors according to body mass index (BMI).
      PARTICIPANTS: Two hundred ninety college students completed the intervention from
      January to February 2005. METHODS: Participants wore pedometers 5 days per week
      for 12 weeks and completed questionnaires assessing demographic information. The
      authors calculated daily step averages for weeks 1, 6, and 12. They then
      classified students as underweight (UW), normal weight (NW), or overweight/obese,
      by BMI. The authors analyzed data using repeated-measures analysis of variance.
      RESULTS: The average number of daily steps increased from week 1 to week 6 (p <
      .001) and week 12 (p = .002). UW participants reported the fewest steps at each
      time point, but the difference was significant only when compared with NW
      participants (p = .03). CONCLUSIONS: These results support the effectiveness of a
      pedometer intervention to increase walking in college students. Health benefits
      other than weight management should be emphasized to maximize the effects for all
      students.

PMID- 18809533
TI  - Prevalence of DSM-IV major depression among Spanish university students.
AB  - OBJECTIVE: The authors' purpose in this study was to estimate prevalence and
      correlates of Diagnostic and Statistical Manual of Mental Disorders, 4th edition
      (DSM-IV), major depressive episodes (MDEs) among Spanish university students.
      PARTICIPANTS AND METHODS: In October and November 2004, interviewers administered
      a screening tool to a sample of 554 students aged 18-34 years (65.9% women).
      RESULTS: The prevalence of MDEs was 8.7% (95% confidence interval = 6.5%-11.3%).
      The most common symptoms were depressed mood (81.3%) and altered sleep (79.2%).
      MDEs were more prevalent among women than men (p < .05). The mean number of
      previous episodes of depression among currently depressed students with previous
      episodes was 2.2 (SD = 1.4). Of depressed students, 0.6% had considered suicide
      and 0.2% had attempted suicide. CONCLUSIONS: Depression was highly prevalent
      among university students. The results suggest the need to develop some type of
      program or service for university students with the aim of preventing depression
      and improving their adaptation to university life.

PMID- 18809534
TI  - Mental health among college students: do those who need services know about and
      use them?
AB  - OBJECTIVE: The objective of this study was to examine connections between
      university students' mental health and their knowledge and use of campus mental
      health services. PARTICIPANTS AND METHODS: In March 2001, a sample of
      undergraduate students (N = 266) completed a Web-based questionnaire, providing
      information related to their mental health, knowledge of mental health services,
      and use of those services. RESULTS: Students who were mentally distressed were
      more likely to know about and use services; however, some students who reported
      to be mentally distressed either did not know about services or knew about
      services but did not use them. Living off campus, identifying as male, and having
      fewer years in college were related to less knowledge of campus mental health
      services. In addition, female sex and number of years in college were predictive
      of higher service use. CONCLUSIONS: With the high prevalence rates and severity
      of mental health problems, university mental health providers must continue to
      make strategic efforts to disseminate knowledge about mental health services to
      all students.

PMID- 18809535
TI  - Socioeconomic correlates of current and regular smoking among college students in
      Rhode Island.
AB  - OBJECTIVE: The objective of this study was to determine how sociodemographic
      variables, in particular socioeconomic status, correlate with current and regular
      smoking among college students in Rhode Island. PARTICIPANTS AND METHODS: Over a
      4-year period (academic year 2000--2001 to 2003--2004), the authors examined
      sociodemographic correlates of cigarette use among 3,984 students aged 17 to 24
      years from 10 colleges and universities in Rhode Island. RESULTS: One-third of
      participants (32.0%) had smoked a cigarette in the 30 days preceding the
      questionnaire. Findings from a pair of logistic regression models indicated that
      participants from upper-income families were more likely to be current smokers-
      although not regular smokers--suggesting that the effect of socioeconomic status
      on smoking is partly dependent on the level of addiction. In addition, freshmen
      were more likely to be current and regular smokers than were upperclassmen, and
      white students were most likely to be regular smokers. CONCLUSIONS: The frequency
      of college students who reported that they first tried smoking and first smoked
      regularly while in college increased from freshman to senior year, indicating
      that the college years are a vulnerable period for smoking initiation and
      habituation.

PMID- 18809536
TI  - Psychosocial factors and low back pain among college students.
AB  - OBJECTIVE AND PARTICIPANTS: The authors evaluated psychosocial factors of stress
      and their effects on the prevalence of low back pain (LBP) among a population of
      college students in a major university in Colorado. METHODS: This was a nested
      cross-sectional study of 973 respondents who completed the National College
      Health Assessment survey. The authors evaluated a subset of questions pertaining
      to psychosocial stressors against the presence of LBP. RESULTS: The annual
      prevalence of LBP among the population studied was 42.8%. The stressful
      psychosocial variables of feeling very sad, exhausted, and overwhelmed were
      associated with the prevalence of LBP. CONCLUSIONS: The prevalence of LBP among
      this younger population is significant and understudied.

PMID- 18809537
TI  - Perceived continuing education needs and job relevance of health education
      competencies among health education and promotion practitioners in college health
      settings.
AB  - OBJECTIVE AND PARTICIPANTS: The author conducted this study to determine college
      health education and promotion practitioners' perceived continuing education
      needs and perceived job relevance in relation to national health education
      responsibilities and competencies. METHODS: In Spring 2006, the author invited
      college health education and promotion professionals to participate in an online
      survey, using 3 listservs. Of 276 individuals visiting the Web site, 141
      participants completed the survey (51%). Participants rated their perceived
      training needs and job relevance for the 35 National Commission for Health
      Education Credentialing (NCHEC) competencies as well as preferred training
      formats. RESULTS: Participants identified the following competencies as those in
      which they needed additional training: designing data-collection instruments,
      securing fiscal resources, interpreting evaluation and research results, carrying
      out evaluation and research plans, and developing plans for evaluation and
      research. They identified the following competencies as being the most relevant
      to their jobs: demonstrating a variety of skills in delivering strategies,
      interventions, and programs; using a variety of methods to implement strategies,
      interventions, and programs; initiating a plan of action; and using health
      related information resources. The most preferred methods of obtaining additional
      continuing education were attending the American College Health Association
      annual meeting (67%) and completing home self-study print materials (67%).
      CONCLUSIONS: Collegiate professional organizations should offer a variety of
      continuing education opportunities centering on NCHEC competencies, specifically
      those perceived as needed by study participants.

PMID- 18809538
TI  - Nonmedical prescription drug use among college students: a comparison between
      athletes and nonathletes.
AB  - OBJECTIVE: Given the substantial increase in nonmedical prescription drug use in
      recent years and a lack of research on the topic, the author analyzed data on
      nonmedical prescription drug use among college students. PARTICIPANTS AND
      METHODS: Using data from the 2001 College Alcohol Study (N = 10,904), the author
      examined variation in nonmedical prescription drug use on the basis of athletic
      involvement. Previous research shows that college athletes are at greater risk
      for certain types of substance use. RESULTS: Findings indicate that athletes are
      less likely to report nonmedical prescription drug use than are nonathletes.
      CONCLUSIONS: This shows that involvement in athletics, especially for women, is a
      protective factor for substance use among college students.

PMID- 18809539
TI  - The protective function of meaning of life on life satisfaction among Chinese
      students in Australia and Hong Kong: a cross-cultural comparative study.
AB  - OBJECTIVE: The authors compared the predictive effects of acculturative stressors
      and meaning of life on life satisfaction between Chinese students in Australia
      and in Hong Kong. PARTICIPANTS: In 2006, the researchers recruited 606 Chinese
      students studying abroad at the University of Melbourne in Australia and at 6
      universities in Hong Kong. METHODS: Participants completed a questionnaire that
      included measures of acculturative stressors, meaning of life, life satisfaction,
      and demographic information. RESULTS: The Australian sample experienced a
      significantly higher level of acculturative stressors than did the Hong Kong
      sample, but life satisfaction did not differ significantly between the 2 samples.
      Meaning of life had a strong positive contribution and acculturative stressors
      had a negative contribution in predicting life satisfaction in both samples.
      Meaning of life partially mediated the relationship between acculturative
      stressors and life satisfaction in both samples. CONCLUSIONS: The authors discuss
      the theoretical and practical implications for Chinese students studying abroad.

PMID- 18809540
TI  - Roles of organizers and champions in building campus-community prevention
      partnerships.
AB  - OBJECTIVE: A campus-community partnership can be an effective vehicle for
      launching environmental strategies to prevent college alcohol-related problems.
      In this study, the authors' primary aim was identifying key factors that
      facilitate or impede colleges' efforts to build campus-community partnerships.
      PARTICIPANTS AND METHODS: From fall 2004 to summer 2006, administrators at five 4
      year colleges participated in a multisite case study. Level of partnership
      development was the primary outcome. RESULTS: Three interrelated factors
      facilitated higher-developed partnerships: college staff assigned to facilitate
      the partnerships who worked as community organizers, higher-level college
      administrators who served as aggressive champions, and community initiation of
      the partnership. The authors did not observe this trio of factors among the less
      developed partnerships. A lack of administrative support made it more difficult
      for a champion to emerge, a college administrator who staunchly advocated for a
      campus-community partnership, and for those assigned to facilitate the
      partnership to carry out their work. CONCLUSIONS: Colleges should appoint higher
      level administrators to serve as champions, while also ensuring that those
      assigned to facilitate a partnership can apply community organizing skills.

PMID- 18809541
TI  - Motivational signage increases physical activity on a college campus.
AB  - OBJECTIVE: The authors evaluated whether motivational signage influenced rates of
      stair use relative to elevator use on a college campus. PARTICIPANTS: In March
      and April 2004, the authors observed students, faculty, staff, and any visitors
      accessing a college campus building. METHODS: During Phase I, the authors
      monitored ascending stair and elevator use at the same time each weekday (Monday
      Friday). During Phase II, the authors placed motivational signs encouraging stair
      use at the bottom of the stairs and outside and inside the elevators. During the
      third week (Phase III), the authors removed the signs. RESULTS: The authors
      observed 18,389 ascending trips during the 3 weeks of the study. Motivational
      signs significantly contributed to an 18.6% increase in stair use in the second
      week, which was maintained in the following week. CONCLUSIONS: The signage
      intervention successfully enhanced physical activity on a college campus by
      providing educational health tips that may have served as motivation to choose
      the stairs.

PMID- 18809542
TI  - Internet and mobile phone text messaging intervention for college smokers.
AB  - OBJECTIVE: The authors developed a smoking cessation program using mobile phone
      text messaging to provide tailored and stage-specific messages to college
      smokers. PARTICIPANTS AND METHODS: The authors recruited 31 daily smokers who
      desired to quit from a college campus and asked them to use an Internet and
      mobile phone text messaging program to quit smoking. RESULTS: Six weeks after
      program initiation, 45% reported abstinence with 42% abstinent based on cotinine
      verification. Continued smokers reported significantly reduced smoking rates and
      dependence. Overall, participants accepted the text messages. CONCLUSIONS: These
      results replicate findings from an earlier study and indicate that mobile phone
      text messaging is a potentially efficacious and easily disseminated method for
      providing cessation interventions to young adult smokers.

PMID- 18809543
TI  - Perfectionism and binge drinking in Canadian students making the transition to
      university.
AB  - OBJECTIVE: In September 2005, the authors explored the relationship between
      perfectionism and binge drinking in a sample of first-year college students.
      PARTICIPANTS: The authors recruited 207 first-year college students (76 men, 131
      women) to complete the Multidimensional Perfectionism Scale (MPS) and Frost
      Multidimensional Perfectionism Scale (F-MPS). METHODS: The authors divided
      participants into 3 groups on the basis of frequency of binge drinking and
      conducted multivariate analyses of variance to compare the binge drinking groups
      on the 3 MPS subscales and the 5 F-MPS subscales. RESULTS: The group with 2 or
      more binge drinking episodes in the past 2 weeks had higher levels of parental
      criticism and lower levels of self-oriented perfectionism, but they did not have
      lower scores on a measure of personal standards. CONCLUSIONS: These findings
      suggest that certain perfectionists binge drink in response to harsh parental
      treatment and that, at least initially, the pursuit of extreme standards of
      personal perfection is incompatible with binge drinking. The authors discuss the
      theoretical and practical implications of these findings.

PMID- 18809544
TI  - An intracellularly inducible gene involved in virulence and polyphosphate
      production in Francisella.
AB  - Francisella tularensis is an intracellular pathogen capable of multiplying to
      high levels in macrophages. By protein analysis, only a few proteins have been
      shown previously to be expressed at high levels in macrophages relative to
      bacteria grown in culture media. To identify additional genes that show increased
      expression during intracellular growth, we developed a plasmid for use in
      Francisella based on the induction of expression of green fluorescent protein.
      Clones of F. tularensis subsp. novicida were identified that were fluorescent
      only intracellularly and not when grown in vitro. Sequencing identified a range
      of genes comprising some such as dnaK that are already known to be expressed
      intracellularly and some novel targets. One of these newly identified regulated
      genes, FTN1472/FTT1564, was selected for further study. Isogenic mutants were
      generated in F. tularensis subsp. novicida and subsp. tularensis by allelic
      replacement. Inactivation of the gene resulted in abolition of polyphosphate
      production by F. novicida, strongly supporting the bioinformatic analysis, which
      had suggested that the gene may encode a polyphosphate kinase. The mutants
      exhibited defects for intracellular growth in macrophages and were attenuated in
      mice, indicating a key role for the putative polyphosphate kinase in the
      virulence of Francisella.

PMID- 18809546
TI  - Molecular detection methods and serotyping performed directly on clinical samples
      improve diagnostic sensitivity and reveal increased incidence of invasive disease
      by Streptococcus pneumoniae in Italian children.
AB  - The aims of this study were to evaluate the incidence of invasive pneumococcal
      disease (IPD) in Italian children and perform serotyping by PCR-based assays
      directly on clinical samples. A 1-year paediatric (0-14 years) population-based
      surveillance study was designed to evaluate the incidence of IPD in the province
      of Florence, Italy, by cultural and molecular methods. Among 92 children (80 with
      pneumonia, 8 with meningitis/sepsis, 4 with arthritis), 4 cases of IPD were
      diagnosed both by culture and real-time PCR and 18 cases exclusively by molecular
      methods. The sensitivity of molecular methods was significantly higher than that
      of cultural methods (Cohen's kappa 0.41; McNemar P=0.000008). The incidence of
      IPD in children below 2 years of age was 11.5/100,000 and 51.8/100,000 by
      cultural and molecular methods, respectively. Pneumococcal serotyping by
      multiplex sequential PCR was obtained in 19/22 samples. Real-time PCR and
      multiplex sequential PCR can be used directly on biological samples, improving
      the ability to diagnose IPD. The incidence of IPD appears 5-10 times higher by
      PCR than by cultural methods.

PMID- 18809545
TI  - Dichotomous metabolism of Enterococcus faecalis induced by haematin starvation
      modulates colonic gene expression.
AB  - Enterococcus faecalis is an intestinal commensal that cannot synthesize
      porphyrins and only expresses a functional respiratory chain when provided with
      exogenous haematin. In the absence of haematin, E. faecalis reverts to
      fermentative metabolism and produces extracellular superoxide that can damage
      epithelial-cell DNA. The acute response of the colonic mucosa to haematin-starved
      E. faecalis was identified by gene array. E. faecalis was inoculated into murine
      colons using a surgical ligation model that preserved tissue architecture and
      homeostasis. The mucosa was exposed to haematin-starved E. faecalis and compared
      with a control consisting of the same strain grown with haematin. At 1 h post
      inoculation, 6 mucosal genes were differentially regulated and this increased to
      42 genes at 6 h. At 6 h, a highly significant biological interaction network was
      identified with functions that included nuclear factor-kappaB (NF-kappaB)
      signalling, apoptosis and cell-cycle regulation. Colon biopsies showed no
      histological abnormalities by haematoxylin and eosin staining.
      Immunohistochemical staining, however, detected NF-kappaB activation in tissue
      macrophages using antibodies to the nuclear localization sequence for p65 and the
      F4/80 marker for murine macrophages. Similarly, haematin-starved E. faecalis
      strongly activated NF-kappaB in murine macrophages in vitro. Furthermore, primary
      and transformed colonic epithelial cells activated the G2/M checkpoint in vitro
      following exposure to haematin-starved E. faecalis. Modulation of this cell-cycle
      checkpoint was due to extracellular superoxide produced as a result of the
      respiratory block in haematin-starved E. faecalis. These results demonstrate that
      the uniquely dichotomous metabolism of E. faecalis can significantly modulate
      gene expression in the colonic mucosa for pathways associated with inflammation,
      apoptosis and cell-cycle regulation.

PMID- 18809547
TI  - A novel method for simple detection of mutations conferring drug resistance in
      Mycobacterium leprae, based on a DNA microarray, and its applicability in
      developing countries.
AB  - A simple method to detect mutations in the genome of Mycobacterium leprae that
      confer resistance to key drugs for leprosy was exploited on the basis of a
      reverse hybridization system. A series of oligonucleotide probes corresponding to
      each mutation in the folP1, rpoB and gyrA genes for dapsone, rifampicin and
      ofloxacin resistance, respectively, were selected and fixed on a glass slide as
      capture probes, to develop a DNA microarray termed the leprosy drug
      susceptibility-DNA microarray (LDS-DA). Mutations in clinical isolates of M.
      leprae were successfully identified by the LDS-DA. Feasibility studies were
      conducted to evaluate the performance of the LDS-DA in two developing countries,
      Myanmar and the Philippines. The high concordance of the results obtained by this
      method with the results of nucleotide sequencing strongly supports the
      applicability of the LDS-DA as a drug susceptibility test in place of sequencing,
      a time-consuming and costly procedure. This is a rapid and simple method for the
      simultaneous susceptibility testing of three front-line drugs for leprosy, and
      solves the problems of previously reported methods.

PMID- 18809548
TI  - An evaluation of the recovery of mycobacteria from urine specimens using the
      automated Mycobacteria Growth Indicator Tube system (BACTEC MGIT 960).
AB  - The Mycobacteria Growth Indicator Tube (MGIT 960) system was evaluated against
      Lowenstein-Jensen (LJ) medium and the BACTEC 460 TB system for the recovery of
      mycobacteria from 1393 consecutive urine specimens. The MGIT had a sensitivity of
      91.3% [95% confidence interval (CI), 83.2-99.4] when the combination of BACTEC
      460 and LJ medium was used as the reference method. The mean time for positivity
      for MGIT and BACTEC 460 was 19.3 days and 20 days, respectively, while that for
      LJ medium was 35 days.The incidence of contamination was highest for LJ medium
      (n=148), followed by MGIT 960 (n=81), and BACTEC 460 had the lowest incidence of
      contamination (n=50). In conclusion, the isolation of mycobacteria from urine
      specimens by the MGIT 960 is comparable to that of the BACTEC 460 TB system and
      solid media.

PMID- 18809549
TI  - Development of a PCR assay for the identification of Salmonella enterica serovar
      Brandenburg.
AB  - Currently, Salmonella enterica serovar Brandenburg is identified serologically on
      the basis of two surface antigens, somatic (O) polysaccharide and flagellar (H)
      proteins. This procedure is time-consuming and requires expensive typing
      reagents. To overcome these problems, a PCR method was developed and validated
      for the identification of S. Brandenburg. Portions of the invA, rfbJ(B), fliC and
      fljB genes were targeted for amplification using four pairs of oligonucleotide
      primers. To validate the assay, genomic DNA from an array of 72 Salmonella
      strains representing 28 serotypes and 5 non-Salmonella strains from 4 different
      genera was subjected to PCR. The four targeted genes were correctly amplified
      only from S. Brandenburg. These results indicate that this PCR assay is a simple,
      rapid, reliable and reproducible method for the identification of S. Brandenburg
      that will aid in surveillance, prevention and control of this pathogen.

PMID- 18809550
TI  - Screening and confirmation of human immunodeficiency virus type 1 infection
      solely by detection of RNA.
AB  - Diagnosis of human immunodeficiency virus (HIV) infection by antibody-based
      testing allows for some recently infected individuals to be falsely assessed as
      non-infected. Since such individuals often have high viral loads and are capable
      of transmitting HIV, it is an imperative public health need to identify these
      individuals. We investigated the feasibility and capability of a diagnostic
      algorithm which included screening and confirmation of HIV infection using only
      nucleic-acid-based tests. This investigation involved screening 1361
      prospectively collected specimens using antibody-based methods in parallel to
      simultaneously testing the same specimens by a qualitative HIV RNA detection
      method (APTIMA HIV-1). Specimens that were positive by antibody screening were
      confirmed by either immunofluorescent assay or Western blotting, while specimens
      positive by RNA screening were confirmed by real-time RT-PCR. In the course of
      the study, 27 specimens were found to contain either HIV antibody or HIV RNA.
      Twenty-six of the 27 specimens were HIV RNA positive, while 23 of the 27
      specimens were antibody positive. One specimen was found which possessed HIV
      antibody but was assessed as negative by the HIV RNA screening test. Four
      specimens were found to contain detectable HIV RNA but were negative by the
      antibody screening test. Three of these four patients were negative at point-of
      care by rapid test, while one was negative by enzyme immunoassay. These data
      indicate that screening and confirmation of HIV infection by RNA methods alone,
      if affordable, may constitute an effective alternative HIV diagnostic algorithm
      in certain settings.

PMID- 18809551
TI  - An unexpectedly high prevalence of colonization with the intestinal spirochaete
      Brachyspira aalborgi amongst residents of the Indonesian island of Bali.
AB  - PCR assays designed to amplify DNA from the anaerobic intestinal spirochaete
      Brachyspira aalborgi were conducted on DNA extracted from 938 faecal samples from
      469 residents on the Indonesian island of Bali. The individuals tested were
      sampled twice in one year and were from four rural villages, one peri-urban
      centre and the capital city, Denpasar. Overall, an unexpectedly high prevalence
      of colonization (24.7%) was found, with prevalence rates at different locations
      varying from a low of 15.6% at one village to 41.5% in the peri-urban centre.
      Comparison of prevalence rates at the two sampling times suggested that, in many
      individuals, colonization was likely to be prolonged (>3 months) and/or that
      reinfection was occurring frequently in these people. Analysis of a questionnaire
      administered to the individuals who were sampled identified specific risk factors
      for colonization as location, co-colonization with the related intestinal
      spirochaete Brachyspira pilosicoli and use of drinking water obtained from wells
      rather than from taps. No specific associations with clinical symptoms were
      identified.

PMID- 18809552
TI  - Superantigen genes in group A streptococcal isolates and their relationship with
      emm types.
AB  - Superantigens are important virulence factors in the pathogenesis of invasive
      disease caused by group A streptococcus (GAS). There has been a recent re
      emergence of this disease worldwide. A number of novel superantigens have been
      described recently. This study investigated 107 isolates of GAS for possession of
      each of the 11 currently known superantigen genes to determine the prevalence, co
      occurrence and genetic restriction amongst different emm types of GAS. The
      results were compared with those in previously published studies. Superantigen
      genes were not randomly distributed amongst GAS isolates. Certain combinations of
      superantigen genes were more common and the majority of emm types showed
      restricted superantigen profiles. This is the first prevalence study of GAS
      isolates to include the complete range of known superantigen genes and their
      restriction amongst emm types. This study contributes to the understanding of the
      relationship between superantigen genes and emm types, and highlights the
      importance of comprehensive studies in different populations.

PMID- 18809553
TI  - Rising prevalence of enteric fever due to multidrug-resistant Salmonella: an
      epidemiological study.
AB  - A prospective study of the prevalent aetiology of enteric fever was undertaken at
      a tertiary care hospital in North India at intervals of every 3 years. Salmonella
      spp. were isolated from 174 (7%) patients. Amongst these, 140 (80%) patients were
      infected by Salmonella enterica subspecies enterica serovar Typhi (S. Typhi) and
      16 (9%) by S. enterica serovar Paratyphi A; the remaining 11% were infected by
      other S. enterica serogroups, Typhimurium, Paratyphi C and Senftenberg, and other
      group E salmonella. A significantly greater number of S. Typhi were isolated in
      the summer and monsoon months. Multidrug resistance (resistance to
      chloramphenicol, ampicillin and co-trimoxazole) sequentially increased from 34%
      in 1999 to 66% in 2005. Increasing resistance was also noticed to the other
      antibiotics, especially to the cephalosporins. Moreover 8% of the S. Typhi
      isolates were found to be presumptive extended spectrum beta-lactamase producers.
      There was a gradual development of resistance to fluoroquinolones over the 7
      years. No resistance was observed to fluoroquinolones in 1999, while in 2005 4.4%
      resistance was observed to sparfloxacin, 8.8% resistance to ofloxacin and a high
      resistance, 13%, to ciprofloxacin. This is an alarming development and it is of
      paramount importance to limit unnecessary use of fluoroquinolones and third
      generation cephalosporins so that their efficacy against salmonella is not
      jeopardized further.

PMID- 18809554
TI  - Molecular epidemiology and antimicrobial susceptibilities of 273 exfoliative
      toxin-encoding-gene-positive Staphylococcus aureus isolates from patients with
      impetigo in Japan.
AB  - The molecular epidemiology and antimicrobial susceptibilities of 273
      Staphylococcus aureus isolates positive for the exfoliative toxin-encoding gene
      obtained from patients with impetigo in Japan in 2006 were studied. The mecA gene
      was detected in 74 meticillin-resistant S. aureus (MRSA) and 23 meticillin
      susceptible S. aureus (MSSA) isolates. All isolates with the staphylococcal
      cassette chromosome (SCC) mec were classified into type IV (92.8%, 90/97) or V
      (7.2%, 7/97). The ET-encoding gene etb was found primarily in strains with mecA
      (87.7%, 71/81), whilst eta (86.6%, 161/186) was detected mainly in strains
      without mecA. The chromosomal enterotoxin-encoding gene cluster egc was found in
      83.0% of strains with eta, whilst no enterotoxin-encoding gene was detected in
      strains with only etb. PFGE showed that each strain carrying eta, etb and etd
      could be classified into distinct groups. The susceptibility profiles of MRSA to
      antimicrobial agents excluding beta-lactams were similar to those of MSSA.
      Gentamicin- and clarithromycin-resistant strains were frequently found for both
      MRSA and MSSA. The aminoglycoside-resistance gene aacA-aphD was detected in 97.3%
      of MRSA and 85.4% of MSSA. Additionally, the macrolide-resistance gene ermA or
      ermC was detected in 67.6% of MRSA and 71.4% of MSSA. Therefore, these results
      suggest that SCCmec types IV or V have spread, particularly in MSSA carrying etb
      in the community.

PMID- 18809555
TI  - Current epidemiology of intracranial abscesses: a prospective 5 year study.
AB  - Intracranial abscesses remain a significant health-care problem in developing
      countries. In view of this, we undertook a comprehensive study to determine the
      demographics and bacteriological spectrum of brain abscesses in our hospital.
      Bacteriological profiles and antibiograms were studied by conventional
      microbiological methods. Seventy-five patients were admitted with brain abscesses
      over a 5 year period (2001-2005). There was 9.5% mortality in patients included
      in this study. The most important factors influencing mortality from intracranial
      abscess were the age and neurological condition of the patient at the time of
      admission. Brain abscess could develop at any age but there was a preponderance
      of males over females. Chronic suppurative otitis media was the most common
      predisposing factor for temporal lobe infections. Forty-one (54.70%) abscesses
      were found to be due to pyogenic organisms, 4% due to Mycobacterium tuberculosis
      and 1.3% were due to Cladophialophora bantiana. The majority of microbial
      isolates were sensitive to the therapeutic regime adopted in our neurosurgery
      unit (cefotaxime, gentamicin and metronidazole). Chloramphenicol is another
      antibiotic with in vitro activity against the isolates.

PMID- 18809556
TI  - Comparison of serum and whole-blood specimens for the detection of Candida DNA in
      critically ill, non-neutropenic patients.
AB  - In contrast to the multitude of studies on fungal PCR assay methods, little work
      has been reported evaluating Candida PCR performance when using whole blood
      compared with serum in candidaemic patients. Here, a comparison of the
      performance of whole-blood and serum specimens using a set of real-time PCR
      Candida species assays is described. Specimens were collected prospectively from
      non-neutropenic adults who were recruited to a diagnostic clinical trial, the
      primary purpose of which was to verify the performance of the assays using serum;
      in all, 104 participants also had whole-blood specimens submitted for analysis in
      addition to the serum specimen. Of these participants, 10 had laboratory
      confirmed candidaemia and 94 were categorized as being 'unlikely' to have
      invasive Candida infection. PCR results from the whole-blood specimens are
      presented here and compared with the results from serum specimens in this
      subgroup among whom both specimen types were obtained contemporaneously. All
      participants with candidaemia were PCR-positive from serum samples; however, only
      seven were PCR-positive from whole blood. All specimens from patients in the
      'unlikely' category were PCR-negative in both types of specimen. Moreover, DNA
      extraction from serum required 1 h; extraction from whole blood required
      approximately 3 h. These data tentatively suggest that, overall, serum is an
      appropriate specimen for Candida PCR for detection of candidaemia in non
      neutropenic adults.

PMID- 18809557
TI  - Plasmid-borne armA methylase gene, together with blaCTX-M-15 and blaTEM-1, in a
      Klebsiella oxytoca isolate from China.
AB  - An armA-producing Klebsiella oxytoca isolate, strain 157, was detected after
      screening of 447 extended-spectrum beta-lactamase-producing Enterobacteriaceae
      isolates in China. K. oxytoca 157 was resistant to aminoglycosides, ciprofloxacin
      and most beta-lactams. Resistance to aminoglycosides and beta-lactams could be
      transferred to recipient Escherichia coli by conjugation. armA, blaCTX-M-15 and
      blaTEM-1 genes were detected in K. oxytoca 157 and transconjugant E. coli strain
      600(pEC157). Mutation of aa 87 in GyrA was found in K. oxytoca 157. A plasmid of
      approximately 55 kb was extracted from K. oxytoca 157(pKO157) and E. coli
      600(pEC157). Southern blot hybridization confirmed that the armA, blaCTX-M-15 and
      blaTEM-1 genes were all located on this conjugative plasmid (pEC157). PCR mapping
      was also performed to investigate the genetic environment of armA. The armA gene
      was found to be flanked by the same putative transposable elements as reported
      previously in E. coli, Klebsiella pneumoniae and Citrobacter freundii isolates
      from different countries.

PMID- 18809558
TI  - Phenotypic evaluation of the effect of anaerobiosis on some virulence attributes
      of Candida albicans.
AB  - The current assumption that Candida albicans is a facultatively anaerobic
      organism has been widely accepted since its recovery from anoxic sites became
      common. However, the link between anaerobiosis and virulence remains uncertain.
      This study investigated the differential cell-surface hydrophobicity (CSH) using
      a hydrocarbon/water partition technique and analysed the differential secretion
      rates of secretory aspartyl proteases (Saps), esterase, chondroitinase and
      haemolysins of C. albicans strains recovered from periodontal pockets and non
      periodontium-related intra-oral sites. For the enzymic tests, all strains from
      both sets were grown under aerobic and anaerobic conditions and the harvested
      cells were inoculated onto suitable normal or pre-reduced culture media in the
      presence or absence of molecular oxygen, respectively. The results showed that no
      variations were perceptible for CSH and chondroitinase (P>0.05). The secretion
      rates of esterase and haemolysins strongly decreased in an anoxic environment
      (P<0.0001). However, a consistent increment (P<0.0001) in Sap secretion was
      detected when cultures were grown under anaerobic conditions. Based on these
      results, it is suggested that the oxygen concentration in the atmosphere
      surrounding cells exerts a variable influence on the virulence attributes of C.
      albicans.

PMID- 18809559
TI  - Detection of Haemophilus influenzae type B DNA in a murine pneumonia model by in
      situ PCR.
AB  - This study estimated the value of in situ PCR (ISPCR) in the detection of
      Haemophilus influenzae type b (Hib) DNA in paraffin-embedded lung tissues of a
      murine pneumonia model. ICR mice were infected with Hib solution intranasally. In
      study group A (n=20), physiological changes and the number of deaths were
      recorded for 7 consecutive days after infection. In study group B (n=10), blood
      samples and lung tissues were obtained from the infected mice on the brink of
      death. In both groups, portions of the lung tissue were cultured for Hib, while
      other portions were submitted for histopathological studies. Conventional PCR,
      PCR followed by Southern blotting and ISPCR were performed to detect Hib in
      paraffin-embedded lung tissues. In control group A, six mice were inoculated
      intranasally with the same concentration of heat-inactivated Hib solution. In
      control group B, six healthy mice served as a blank control. Both control groups
      were managed using the same methods as those used in the study groups. The white
      blood cell count of the mice in the study group increased (F=3.295, P<0.01), with
      a high neutrophil count (F=0.127, P<0.05). In the histopathological study,
      various stages of pneumonia were found in the lung tissues of the infected mice
      examined by microscope; 80% of the mice had moderate or severe pneumonia.
      Cultures of lung tissues in the study groups were all positive for Hib, while no
      bacteria were found in the control groups. Hib was detected in only 4 of 30
      samples (13.3%) of the study groups using conventional PCR, but in all 30 samples
      (100%) using both Southern blotting and ISPCR. All three methods did not detect
      Hib in the control groups. Because of its sensitivity and specificity and its
      ability to locate the micro-organism, ISPCR can be considered suitable for the
      detection of Hib in paraffin-embedded lung tissues.

PMID- 18809560
TI  - Coccidioidal pericarditis: a rapid presumptive diagnosis by an in-house antigen
      confirmed by mycological and molecular methods.
AB  - Coccidioidal pericarditis is a condition found in approximately 1-5% of patients
      infected by Coccidioides species. It is associated with widely diverse clinical
      symptoms. This paper reports a case of coccidioidal pericarditis diagnosed by an
      in-house Coccidioides posadasii antigen and confirmed with mycological and
      molecular methods. From February to September 2005, the patient suffered from
      fever, weight loss, a non-productive cough, thoracic pain and tachycardia. He
      received a positive diagnosis of coccidioidal pericarditis only in October 2005.
      The macromorphological examination of the culture showed a whitish felt-like
      colony, which became brownish with age. Preparations in lactophenol cotton blue
      stain showed hyaline septate hyphae with fragmentation and thin arthroconidia
      like structures. Pericardial fluid and sera samples were positive for
      Coccidioides antibodies by immunodiffusion and ELISA with a C. posadasii in-house
      antigen preparation. The C. posadasii identification was confirmed by nested PCR
      of the antigen 2/proline-rich antigen (Ag2/PRA) encoding gene.

PMID- 18809561
TI  - Successful treatment of Chromobacterium violaceum sepsis in South Africa.
AB  - Chromobacterium violaceum sepsis is extremely rare and usually fatal. A very few
      cases of C. violaceum infection have been reported from Africa, but never from
      South Africa. As far as could be ascertained, this infection has never been
      reported in a patient with leukaemia. We describe what we believe to be the first
      such case of C. violaceum sepsis, in a 16-year-old female patient with acute
      biphenotypic leukaemia, which developed during the neutropenic phase after
      intensive chemotherapy. The infection was due to a non-pigmented strain of C.
      violaceum and was associated with a co-infection with Candida parapsilosis; both
      were successfully treated using broad-spectrum antibiotics, antifungals and
      removal of a Hickman line.

PMID- 18809562
TI  - Two fatal cases of psittacosis caused by Chlamydophila psittaci.
AB  - Two fatal cases of psittacosis are described in two poultry-processing-plant
      employees presenting with pneumonia and respiratory failure. Diagnosis was
      confirmed by serological and PCR methods. Psittacosis due to Chlamydophila
      psittaci infection usually has a good recovery rate, although diagnostic delay
      and mistreatment can lead to severe complications and even death. This report
      emphasizes the need for rapid differential diagnosis and management of suspected
      cases of atypical pneumonia to prevent fatal outcomes.

PMID- 18809563
TI  - Endocarditis due to Corynebacterium amycolatum.
AB  - Corynebacterium amycolatum, a normal inhabitant of human skin, is a Gram
      positive, non-spore-forming, mycolic acid-free, aerobic or facultative anaerobic
      bacillus. Since its description in 1988, it has only rarely been associated with
      infective endocarditis. This paper describes a case of infective endocarditis
      successfully treated by combination therapy with daptomycin and rifampicin. To
      the best of our knowledge, this is the first case report of C. amycolatum
      endocarditis from the USA successfully treated with these agents.

PMID- 18809564
TI  - Neonatal sepsis caused by a CTX-M-32-producing Escherichia coli isolate.
AB  - We describe what we believe to be the first case of neonatal sepsis caused by CTX
      M-producing Escherichia coli, in a low-weight preterm infant, born to a colonized
      mother who had received antibiotic treatment antepartum. Increased dissemination
      of extended-spectrum beta-lactamase-producing E. coli in the community should be
      borne in mind for empirical therapy of sepsis in high-risk newborns.

PMID- 18809565
TI  - LightCycler SeptiFast assay as a tool for the rapid diagnosis of sepsis in
      patients during antimicrobial therapy.

PMID- 18809566
TI  - Comparison of PFGE and multilocus sequence typing for analysis of Klebsiella
      pneumoniae isolates.

PMID- 18809567
TI  - Septic arthritis due to Haemophilus influenzae serotype a in the post-vaccination
      era in Brazil.

PMID- 18809568
TI  - Histone modifications, but not nucleosomal positioning, correlate with major
      histocompatibility complex class I promoter activity in different tissues in
      vivo.
AB  - To examine the role of chromatin in transcriptional regulation of the major
      histocompatibility complex (MHC) class I gene, we determined nucleosome occupancy
      and positioning, histone modifications, and H2A.Z occupancy across its regulatory
      region in murine tissues that have widely different expression levels.
      Surprisingly, nucleosome occupancy and positioning were indistinguishable between
      the spleen, kidney, and brain. In all three tissues, the 200 bp upstream of the
      transcription start site had low nucleosome occupancy. In contrast, nuclease
      hypersensitivity, histone modifications, and H2A.Z occupancy showed tissue
      specific differences. Thus, tissue-specific differences in MHC class I
      transcription correlate with histone modifications and not nucleosomal
      organization. Further, activation of class I transcription by gamma interferon or
      its inhibition by alpha-amanitin did not alter nucleosome occupancy, positioning,
      nuclease hypersensitivity, histone modifications, or H2A.Z occupancy in any of
      the tissues examined. Thus, chromatin remodeling was not required to dynamically
      modulate transcriptional levels. These findings suggest that the MHC class I
      promoter remains poised and accessible to rapidly respond to infection and
      environmental cues.

PMID- 18809569
TI  - Genotoxic stress-induced cyclin D1 phosphorylation and proteolysis are required
      for genomic stability.
AB  - While mitogenic induction of cyclin D1 contributes to cell cycle progression,
      ubiquitin-mediated proteolysis buffers this accumulation and prevents aberrant
      proliferation. Because the failure to degrade cyclin D1 during S-phase triggers
      DNA rereplication, we have investigated cellular regulation of cyclin D1
      following genotoxic stress. These data reveal that expression of cyclin D1
      alleles refractory to phosphorylation- and ubiquitin-mediated degradation
      increase the frequency of chromatid breaks following DNA damage. Double-strand
      break-dependent cyclin D1 degradation requires ATM and GSK3beta, which in turn
      mediate cyclin D1 phosphorylation. Phosphorylated cyclin D1 is targeted for
      proteasomal degradation after ubiquitylation by SCF(Fbx4-alphaBcrystallin). Loss
      of Fbx4-dependent degradation triggers radio-resistant DNA synthesis, thereby
      sensitizing cells to S-phase-specific chemotherapeutic intervention. These data
      suggest that failure to degrade cyclin D1 compromises the intra-S-phase
      checkpoint and suggest that cyclin D1 degradation is a vital cellular response
      necessary to prevent genomic instability following genotoxic insult.

PMID- 18809570
TI  - Balance between distinct HP1 family proteins controls heterochromatin assembly in
      fission yeast.
AB  - Heterochromatin protein 1 (HP1) is a conserved chromosomal protein with important
      roles in chromatin packaging and gene silencing. In fission yeast, two HP1 family
      proteins, Swi6 and Chp2, are involved in transcriptional silencing at
      heterochromatic regions, but how they function and whether they act cooperatively
      or differentially in heterochromatin assembly remain elusive. Here, we show that
      both Swi6 and Chp2 are required for the assembly of fully repressive
      heterochromatin, in which they play distinct, nonoverlapping roles. Swi6 is
      expressed abundantly and plays a dose-dependent role in forming a repressive
      structure through its self-association property. In contrast, Chp2, expressed at
      a lower level, does not show a simple dose-dependent repressive activity.
      However, it contributes to the recruitment of chromatin-modulating factors Clr3
      and Epe1 and possesses a novel ability to bind the chromatin-enriched nuclear
      subfraction that is closely linked with its silencing function. Finally, we
      demonstrate that a proper balance between Swi6 and Chp2 is critical for
      heterochromatin assembly. Our findings provide novel insight into the distinct
      and cooperative functions of multiple HP1 family proteins in the formation of
      higher-order chromatin structure.

PMID- 18809571
TI  - Redundant roles of SMAD2 and SMAD3 in ovarian granulosa cells in vivo.
AB  - Transforming growth factor beta (TGF-beta) superfamily members are critical in
      maintaining cell growth and differentiation in the ovary. Although signaling of
      activins, TGF-betas, growth differentiation factor 9, and nodal converge
      preferentially to SMAD2 and SMAD3, the in vivo functions and redundancy of these
      SMADs in the ovary and female reproduction remain largely unidentified. To
      circumvent the deleterious phenotypic aspects of ubiquitous deletion of Smad2 and
      Smad3, a conditional knockout strategy was formulated to selectively inactivate
      Smad2, Smad3, or both Smad2 and Smad3 in ovarian granulosa cells. While granulosa
      cell ablation of individual Smad2 or Smad3 caused insignificant changes in female
      fertility, deletion of both Smad2 and Smad3 led to dramatically reduced female
      fertility and fecundity. These defects were associated with the disruption of
      multiple ovarian processes, including follicular development, ovulation, and
      cumulus cell expansion. Furthermore, the impaired expansion of cumulus cells may
      be partially associated with altered cumulus expansion-related transcripts that
      are regulated by SMAD2/3 signaling. Our results indicate that SMAD2 and SMAD3
      function redundantly in vivo to maintain normal female fertility and further
      support the involvement of an intraovarian SMAD2/3 pathway in mediating oocyte
      produced signals essential for coordinating key events of the ovulatory process.

PMID- 18809572
TI  - Acetylation of Rsc4p by Gcn5p is essential in the absence of histone H3
      acetylation.
AB  - Rsc4p, a subunit of the RSC chromatin-remodeling complex, is acetylated at lysine
      25 by Gcn5p, a well-characterized histone acetyltransferase (HAT). Mutation of
      lysine 25 does not result in a significant growth defect, and therefore whether
      this modification is important for the function of the essential RSC complex was
      unknown. In a search to uncover the molecular basis for the lethality resulting
      from loss of multiple histone H3-specific HATs, we determined that loss of Rsc4p
      acetylation is lethal in strains lacking histone H3 acetylation. Phenotype
      comparison of mutants with arginine and glutamine substitutions of acetylatable
      lysines within the histone H3 tail suggests that it is a failure to neutralize
      the charge of the H3 tail that is lethal in strains lacking Rsc4p acetylation. We
      also demonstrate that Rsc4p acetylation does not require any of the known Gcn5p
      dependent HAT complexes and thus represents a truly novel function for Gcn5p.
      These results demonstrate for the first time the vital and yet redundant
      functions of histone H3 and Rsc4p acetylation in maintaining cell viability.

PMID- 18809573
TI  - Glyceraldehyde-3-phosphate dehydrogenase regulates endothelin-1 expression by a
      novel, redox-sensitive mechanism involving mRNA stability.
AB  - The regulation of the synthesis of the endothelial-derived vasoconstrictor
      endothelin-1 (ET-1) is a complex process encompassing transcriptional as well as
      mRNA stability mechanisms. We have described recently the existence of a
      mechanism for the control of ET-1 expression based on the mRNA-destabilizing
      capacity of specific cytosolic proteins through interaction with AU-rich elements
      (AREs) present in the 3' untranslated region of the gene. We now identify
      glyceraldehyde-3'-phosphate dehydrogenase (GAPDH) as a protein which binds to the
      AREs and is responsible for the destabilization of the mRNA. Oxidant stress
      alters the binding of GAPDH to the mRNA and its capacity to modulate ET-1
      expression, a phenomenon occurring through specific S glutathionylation of the
      catalytically active residue Cys 152. Finally, we provide data consistent with a
      role for GAPDH in mRNA unwinding, yielding this molecule more prone to
      degradation. In contrast, S-thiolated GAPDH appears unable to modify mRNA
      unwinding, thus facilitating enhanced stability. Taken together, these results
      describe a novel, redox-based mechanism regulating mRNA stability and add a new
      facet to the panoply of GAPDH cellular homeostatic actions.

PMID- 18809574
TI  - Developmental links between the fetal and adult zones of the adrenal cortex
      revealed by lineage tracing.
AB  - The nuclear receptor Ad4BP/SF-1 is essential for development of the adrenal
      cortex and the gonads, which derive from a common adrenogonadal primordium. The
      adrenal cortex subsequently forms morphologically distinct compartments: the
      inner (fetal) and outer (definitive or adult) zones. Despite considerable effort,
      the mechanisms that mediate the differential development of the adrenal and
      gonadal primordia and the fetal and adult adrenal cortices remain incompletely
      understood. We previously identified a fetal adrenal-specific enhancer (FAdE) in
      the Ad4BP/SF-1 locus that directs transgene expression to the fetal adrenal
      cortex and demonstrated that this enhancer is autoregulated by Ad4BP/SF-1. We now
      combine the FAdE with the Cre/loxP system to trace cell lineages in which the
      FAdE was active at some stage in development. These lineage-tracing studies
      establish definitively that the adult cortex derives from precursor cells in the
      fetal cortex in which the FAdE was activated before the organization into two
      distinct zones. The potential of these fetal adrenocortical cells to enter the
      pathway that eventuates in cells of the adult cortex disappeared by embryonic day
      14.5. Thus, these studies demonstrate a direct link between the fetal and adult
      cortices involving a transition that must occur before a specific stage of
      development.

PMID- 18809575
TI  - Role of the Caenorhabditis elegans Shc adaptor protein in the c-Jun N-terminal
      kinase signaling pathway.
AB  - Mitogen-activated protein kinases (MAPKs) are integral to the mechanisms by which
      cells respond to physiological stimuli and a wide variety of environmental
      stresses. In Caenorhabditis elegans, the stress response is controlled by a c-Jun
      N-terminal kinase (JNK)-like mitogen-activated protein kinase (MAPK) signaling
      pathway, which is regulated by MLK-1 MAPK kinase kinase (MAPKKK), MEK-1 MAPK
      kinase (MAPKK), and KGB-1 JNK-like MAPK. In this study, we identify the shc-1
      gene, which encodes a C. elegans homolog of Shc, as a factor that specifically
      interacts with MEK-1. The shc-1 loss-of-function mutation is defective in
      activation of KGB-1, resulting in hypersensitivity to heavy metals. A specific
      tyrosine residue in the NPXY motif of MLK-1 creates a docking site for SHC-1 with
      the phosphotyrosine binding (PTB) domain. Introduction of a mutation that
      perturbs binding to the PTB domain or the NPXY motif abolishes the function of
      SHC-1 or MLK-1, respectively, thereby abolishing the resistance to heavy metal
      stress. These results suggest that SHC-1 acts as a scaffold to link MAPKKK to
      MAPKK activation in the KGB-1 MAPK signal transduction pathway.

PMID- 18809576
TI  - Dual roles for NFAT transcription factor genes as oncogenes and tumor
      suppressors.
AB  - Nuclear factor of activated T cells (NFAT) was first described as an activation
      and differentiation transcription factor in lymphocytes. Several in vitro studies
      suggest that NFAT family members are redundant proteins. However, analysis of
      mice deficient for NFAT proteins suggested different roles for the NFAT family of
      transcription factors in the regulation of cell proliferation and apoptosis. NFAT
      may also regulate several cell cycle and survival factors influencing tumor
      growth and survival. Here, we demonstrate that two constitutively active forms of
      NFAT proteins (CA-NFAT1 and CA-NFAT2 short isoform) induce distinct phenotypes in
      NIH 3T3 cells. Whereas CA-NFAT1 expression induces cell cycle arrest and
      apoptosis in NIH 3T3 fibroblasts, CA-NFAT2 short isoform leads to increased
      proliferation capacity and induction of cell transformation. Furthermore, NFAT1
      deficient mice showed an increased propensity for chemical carcinogen-induced
      tumor formation, and CA-NFAT1 expression subverted the transformation of NIH 3T3
      cells induced by the H-rasV12 oncogene. The differential roles for NFAT1 are at
      least partially due to the protein C-terminal domain. These results suggest that
      the NFAT1 gene acts as a tumor suppressor gene and the NFAT2 short isoform acts
      gene as an oncogene, supporting different roles for the two transcription factors
      in tumor development.

PMID- 18809577
TI  - MCAK-independent functions of ch-Tog/XMAP215 in microtubule plus-end dynamics.
AB  - The formation of a functional bipolar mitotic spindle is essential for genetic
      integrity. In human cells, the microtubule polymerase XMAP215/ch-Tog ensures
      spindle bipolarity by counteracting the activity of the microtubule
      depolymerizing kinesin XKCM1/MCAK. Their antagonistic effects on microtubule
      polymerization confer dynamic instability on microtubules assembled in cell-free
      systems. It is, however, unclear if a similar interplay governs microtubule
      behavior in mammalian cells in vivo. Using real-time analysis of spindle
      assembly, we found that ch-Tog is required to produce or maintain long
      centrosomal microtubules after nuclear-envelope breakdown. In the absence of ch
      Tog, microtubule assembly at centrosomes was impaired and microtubules were
      nondynamic. Interkinetochore distances and the lengths of kinetochore fibers were
      also reduced in these cells. Codepleting MCAK with ch-Tog improved kinetochore
      fiber length and interkinetochore separation but, surprisingly, did not rescue
      centrosomal microtubule assembly and microtubule dynamics. Our data therefore
      suggest that ch-Tog has at least two distinct roles in spindle formation. First,
      it protects kinetochore microtubules from depolymerization by MCAK. Second, ch
      Tog plays an essential role in centrosomal microtubule assembly, a function
      independent of MCAK activity. Thus, the notion that the antagonistic activities
      of MCAK and ch-Tog determine overall microtubule stability is too simplistic to
      apply to human cells.

PMID- 18809578
TI  - Superfluous role of mammalian septins 3 and 5 in neuronal development and
      synaptic transmission.
AB  - The septin family of GTPases, first identified for their roles in cell division,
      are also expressed in postmitotic tissues. SEPT3 (G-septin) and SEPT5 (CDCrel-1)
      are highly expressed in neurons, enriched in presynaptic terminals, and
      associated with synaptic vesicles. These characteristics suggest that SEPT3 or
      SEPT5 might be important for synapse formation, maturation, or synaptic vesicle
      traffic. Since Sept5(-/-) mice do not show any overt neurological phenotypes, we
      generated Sept3(-/-) and Sept3(-/-) Sept5(-/-) mice and found that SEPT3 and
      SEPT5 are not essential for development, fertility, or viability. Changes in the
      expression of septins were noted in the absence of SEPT3, SEPT5, and both
      septins. SEPT5 association with other septins in brain tissue was unaffected by
      the removal of SEPT3. No abnormalities were observed in the gross morphology and
      synapses of the hippocampus. Similarly, axon development and synapse formation
      were unaffected in vitro. In cultured hippocampal neurons, the size of the
      recycling synaptic vesicle pool was unaltered in the absence of SEPT3.
      Furthermore, synaptic transmission at two different central synapses was not
      significantly affected in Sept3(-/-) Sept5(-/-) mice. These results indicate that
      SEPT3 and SEPT5 are dispensable for neuronal development as well as for synaptic
      vesicle fusion and recycling.

PMID- 18809579
TI  - PML activates transcription by protecting HIPK2 and p300 from SCFFbx3-mediated
      degradation.
AB  - PML, a nuclear protein, interacts with several transcription factors and their
      coactivators, such as HIPK2 and p300, resulting in the activation of
      transcription. Although PML is thought to achieve transcription activation by
      stabilizing the transcription factor complex, little is known about the
      underlying molecular mechanism. To clarify the role of PML in transcription
      regulation, we purified the PML complex and identified Fbxo3 (Fbx3), Skp1, and
      Cullin1 as novel components of this complex. Fbx3 formed SCF(Fbx3) ubiquitin
      ligase and promoted the degradation of HIPK2 and p300 by the ubiquitin-proteasome
      pathway. PML inhibited this degradation through a mechanism that unexpectedly did
      not involve inhibition of the ubiquitination of HIPK2. PML, Fbx3, and HIPK2
      synergistically activated p53-induced transcription. Our findings suggest that
      PML stabilizes the transcription factor complex by protecting HIPK2 and p300 from
      SCF(Fbx3)-induced degradation until transcription is completed. In contrast, the
      leukemia-associated fusion PML-RARalpha induced the degradation of HIPK2. We
      discuss the roles of PML and PML-retinoic acid receptor alpha, as well as those
      of HIPK2 and p300 ubiquitination, in transcriptional regulation and
      leukemogenesis.

PMID- 18809580
TI  - Dissection of the molecular defects caused by pathogenic mutations in the DNA
      repair factor XPC.
AB  - XPC is responsible for DNA damage sensing in nucleotide excision repair (NER).
      Mutations in XPC lead to a defect in NER and to xeroderma pigmentosum (XP-C).
      Here, we analyzed the biochemical properties behind mutations found within three
      patients: one amino acid substitution (P334H, XP1MI, and GM02096), one amino acid
      incorporation in a conserved domain (697insVal, XP8BE, and GM02249), and a stop
      mutation (R579St, XP67TMA, and GM14867). Using these mutants, we demonstrated
      that HR23B stabilizes XPC on DNA and protects it from degradation. XPC recruits
      the transcription/repair factor TFIIH and stimulates its XPB ATPase activity to
      initiate damaged DNA opening. In an effort to understand the severity of XP-C
      phenotypes, we also demonstrated that single mutations in XPC perturb other
      repair processes, such as base excision repair (e.g., the P334H mutation prevents
      the stimulation of Ogg1 glycosylase because it thwarts the interaction between
      XPC and Ogg1), thereby leading to a deeper understanding of the molecular repair
      defect of the XP-C patients.

PMID- 18809581
TI  - The p85alpha subunit of class IA phosphatidylinositol 3-kinase regulates the
      expression of multiple genes involved in osteoclast maturation and migration.
AB  - Intracellular signals involved in the maturation and function of osteoclasts are
      poorly understood. Here, we demonstrate that osteoclasts express multiple
      regulatory subunits of class I(A) phosphatidylinositol 3-kinase (PI3-K) although
      the expression of the full-length form of p85alpha is most abundant. In vivo,
      deficiency of p85alpha results in a significantly greater number of trabeculae
      and significantly lower spacing between trabeculae as well as increased bone mass
      in both males and females compared to their sex-matched wild-type controls.
      Consistently, p85alpha(-/-) osteoclast progenitors show impaired growth and
      differentiation, which is associated with reduced activation of Akt and mitogen
      activated protein kinase extracellular signal-regulated kinase 1 (Erk1)/Erk2 in
      vitro. Furthermore, a significant reduction in the ability of p85alpha(-/-)
      osteoclasts to adhere to as well as to migrate via integrin alphavbeta3 was
      observed, which was associated with reduced bone resorption. Microarray as well
      as quantitative real-time PCR analysis of p85alpha(-/-) osteoclasts revealed a
      significant reduction in the expression of several genes associated with the
      maturation and migration of osteoclasts, including microphathalmia-associated
      transcription factor, tartrate-resistant acid phosphatase, cathepsin K, and beta3
      integrin. Restoring the expression of the full-length form of p85alpha but not
      the version with a deletion of the Src homology-3 domain restored the maturation
      of p85alpha(-/-) osteoclasts to wild-type levels. These results highlight the
      importance of the full-length version of the p85alpha subunit of class I(A) PI3-K
      in controlling multiple aspects of osteoclast functions.

PMID- 18809582
TI  - Nucleophosmin serves as a rate-limiting nuclear export chaperone for the
      Mammalian ribosome.
AB  - Nucleophosmin (NPM) (B23) is an essential protein in mouse development and cell
      growth; however, it has been assigned numerous roles in very diverse cellular
      processes. Here, we present a unified mechanism for NPM's role in cell growth;
      NPM directs the nuclear export of both 40S and 60S ribosomal subunits. NPM
      interacts with rRNA and large and small ribosomal subunit proteins and also
      colocalizes with large and small ribosomal subunit proteins in the nucleolus,
      nucleus, and cytoplasm. The transduction of NPM shuttling-defective mutants or
      the loss of Npm1 inhibited the nuclear export of both the 40S and 60S ribosomal
      subunits, reduced the available pool of cytoplasmic polysomes, and diminished
      overall protein synthesis without affecting rRNA processing or ribosome assembly.
      While the inhibition of NPM shuttling can block cellular proliferation, the
      dramatic effects on ribosome export occur prior to cell cycle inhibition. Modest
      increases in NPM expression amplified the export of newly synthesized rRNAs,
      resulting in increased rates of protein synthesis and indicating that NPM is rate
      limiting in this pathway. These results support the idea that NPM-regulated
      ribosome export is a fundamental process in cell growth.

PMID- 18809583
TI  - Regulatory role of human AP-endonuclease (APE1/Ref-1) in YB-1-mediated activation
      of the multidrug resistance gene MDR1.
AB  - Human AP-endonuclease (APE1/Ref-1), a central enzyme involved in the repair of
      oxidative base damage and DNA strand breaks, has a second activity as a
      transcriptional regulator that binds to several trans-acting factors. APE1
      overexpression is often observed in tumor cells and confers resistance to various
      anticancer drugs; its downregulation sensitizes tumor cells to such agents.
      Because the involvement of APE1 in repairing the DNA damage induced by many of
      these drugs is unlikely, drug resistance may be linked to APE1's transcriptional
      regulatory function. Here, we show that APE1, preferably in the acetylated form,
      stably interacts with Y-box-binding protein 1 (YB-1) and enhances its binding to
      the Y-box element, leading to the activation of the multidrug resistance gene
      MDR1. The enhanced MDR1 level due to the ectopic expression of wild-type APE1 but
      not of its nonacetylable mutant underscores the importance of APE1's acetylation
      in its coactivator function. APE1 downregulation sensitizes MDR1-overexpressing
      tumor cells to cisplatin or doxorubicin, showing APE1's critical role in YB-1
      mediated gene expression and, thus, drug resistance in tumor cells. A systematic
      increase in both APE1 and MDR1 expression was observed in non-small-cell lung
      cancer tissue samples. Thus, our study has established the novel role of the
      acetylation-mediated transcriptional regulatory function of APE1, making it a
      potential target for the drug sensitization of tumor cells.

PMID- 18809584
TI  - Diet, nutrition and cancer: public, media and scientific confusion.

PMID- 18809585
TI  - Bevacizumab in advanced cancer, too much or too little?

PMID- 18809586
TI  - Long term androgen deprivation therapy in prostate cancer.

PMID- 18809587
TI  - Manchester triage system in paediatric emergency care: prospective observational
      study.
AB  - OBJECTIVE: To validate use of the Manchester triage system in paediatric
      emergency care. DESIGN: Prospective observational study. SETTING: Emergency
      departments of a university hospital and a teaching hospital in the Netherlands,
      2006-7. PARTICIPANTS: 17,600 children (aged <16) visiting an emergency department
      over 13 months (university hospital) and seven months (teaching hospital).
      INTERVENTION: Nurses triaged 16,735/17,600 patients (95%) using a computerised
      Manchester triage system, which calculated urgency levels from the selection of
      discriminators embedded in flowcharts for presenting problems. Nurses over-ruled
      the urgency level in 1714 (10%) children, who were excluded from analysis.
      Complete data for the reference standard were unavailable in 1467 (9%) children
      leaving 13,554 patients for analysis. MAIN OUTCOME MEASURES: Urgency according to
      the Manchester triage system compared with a predefined and independently
      assessed reference standard for five urgency levels. This reference standard was
      based on a combination of vital signs at presentation, potentially life
      threatening conditions, diagnostic resources, therapeutic interventions, and
      follow-up. Sensitivity, specificity, and likelihood ratios for high urgency
      (immediate and very urgent) and 95% confidence intervals for subgroups based on
      age, use of flowcharts, and discriminators. RESULTS: The Manchester urgency level
      agreed with the reference standard in 4582 of 13,554 (34%) children; 7311 (54%)
      were over-triaged and 1661 (12%) under-triaged. The likelihood ratio was 3.0 (95%
      confidence interval 2.8 to 3.2) for high urgency and 0.5 (0.4 to 0.5) for low
      urgency; though the likelihood ratios were lower for those presenting with a
      medical problem (2.3 (2.2 to 2.5) v 12.0 (7.8 to 18.0) for trauma) and in younger
      children (2.4 (1.9 to 2.9) at 0-2 months [corrected] v 5.4 (4.5 to 6.5) at 8-16
      years). CONCLUSIONS: The Manchester triage system has moderate validity in
      paediatric emergency care. It errs on the safe side, with much more over-triage
      than under-triage compared with an independent reference standard for urgency.
      Triage of patients with a medical problem or in younger children is particularly
      difficult.

PMID- 18809588
TI  - Manchester triage system in paediatric emergency care.

PMID- 18809589
TI  - Communicating about screening.

PMID- 18809590
TI  - Research shows that South Africa deserves its poor reputation for tackling AIDS.

PMID- 18809591
TI  - Unicef calls for more action to reduce maternal deaths in developing world.

PMID- 18809592
TI  - The diagnosis and management of parasellar tumours of the pituitary.
AB  - The sellar and parasellar region is an anatomically complex area where a number
      of neoplastic, inflammatory, infectious, developmental and vascular diseases can
      develop. Although most sellar lesions are due to pituitary adenomas, a number of
      other pathologies involving the parasellar region can present in a similar
      manner. The diagnosis of such lesions involves a multidisciplinary approach, and
      detailed endocrinological, ophthalmological, neuroimaging, neurological and
      finally histological studies are required. Correct diagnosis prior to any
      intervention is essential as the treatment of choice will be different for each
      disorder, particularly in the case of primary malignant parasellar tumours. The
      complexity of structures that define the parasellar region can produce a variety
      of neoplastic processes, the malignant potential of which relies on histological
      grading. In the majority of parasellar tumours, a multimodal therapeutic approach
      is frequently necessary including surgery, radiotherapy, primary or adjuvant
      medical treatment and replacement of apparent endocrine deficits. Disease
      specific medical therapies are mandatory in order to prevent recurrence or
      further tumour growth. This is particularly important as neoplastic lesions of
      the parasellar region tend to recur after prolonged follow-up, even when
      optimally treated. Apart from the type of treatment, identification of clinical
      and radiological features that could predict patients with different prognosis
      seems necessary in order to identify high-risk patients. Due to their rarity,
      central registration of parasellar tumours is required in order to be able to
      provide evidence-based diagnostic and mainly therapeutic approaches.

PMID- 18809593
TI  - HIA forecast: cloudy with sunny spells later?

PMID- 18809595
TI  - The need for strategic health assessment.

PMID- 18809596
TI  - Part-time training in pediatric residency programs: principles and practices.
AB  - Despite growing interest in part-time work, few pediatricians are pursuing part
      time residency training. There is currently little guidance for programs or
      residents who wish to design an alternative path through residency. In this
      article we review the need for part-time residencies and address obstacles to be
      overcome in their initiation. Strategies are offered for residents and program
      directors planning part-time training pathways, with recommendations for
      implementation amid a changing environment for graduate medical education. The
      needs of trainees, residency programs, hospitals, and credentialing organizations
      are considered.

PMID- 18809597
TI  - Kawasaki disease in a pediatric intensive care unit: a case-control study.
AB  - OBJECTIVES: We conducted a case-control study to ascertain the clinical
      presentations, risk factors, and clinical outcomes of children who had Kawasaki
      disease and were admitted to the ICU of our children's hospital. METHODS: We
      reviewed charts of all children who had a discharge diagnosis of Kawasaki disease
      and were admitted to the ICU from 1995 through 2007. For each patient, we
      identified 3 season-matched control subjects who had Kawasaki disease and were
      not admitted to the ICU. RESULTS: We identified 423 patients with Kawasaki
      disease. Of those, 14 (3.3%) were admitted to the ICU and met our inclusion
      criteria. ICU admission diagnoses were most commonly toxic shock or septic shock.
      Thirteen (92.8%) of 14 patients who were admitted to the ICU met criteria for
      complete Kawasaki disease before treatment. There was no significant difference
      in age in ICU patients compared with season-matched control subjects with
      Kawasaki disease. ICU patients were significantly more likely to be female and to
      have higher band counts, lower platelet counts, lower albumin levels, and higher
      C-reactive protein values. Time from admission to treatment with intravenous
      immunoglobulin was delayed in ICU patients. ICU patients were more likely to have
      intravenous immunoglobulin-refractory disease and require therapy with a second
      dose of intravenous immunoglobulin, infliximab, or steroids. CONCLUSIONS: We
      present a case-control study of patients who had Kawasaki disease and presented
      severely ill, in shock, and requiring admission to the ICU. These patients
      frequently were misdiagnosed because of failure to appreciate the full spectrum
      of disease severity seen in patients with Kawasaki disease. These patients'
      illnesses was often mistaken for toxic or septic shock, leading to a delay in
      treatment with intravenous immunoglobulin. Patients who have Kawasaki disease and
      are admitted to the ICU are at increased risk for intravenous immunoglobulin
      refractory disease and may be at risk for development of more severe coronary
      artery disease.

PMID- 18809598
TI  - Is fluorouracil-induced severe toxicity in DPYD*2A individuals related to sex or
      to treatment regimen?

PMID- 18809599
TI  - Benefit of robotic assistance in comparing outcomes of minimally invasive versus
      open radical prostatectomy.

PMID- 18809600
TI  - Breast cancer survivors and hot flashes: the search for nonhormonal treatments.

PMID- 18809601
TI  - Missing patient-reported outcome data in an adjuvant lung cancer study.

PMID- 18809602
TI  - Adjuvant chemotherapy for non-small-cell lung cancer: a fading effect?

PMID- 18809603
TI  - Solitary relapse of desmoplastic small round cell tumor detected by positron
      emission tomography/computed tomography.

PMID- 18809604
TI  - Sign of Leser-Trelat in newly diagnosed advanced gastric adenocarcinoma.

PMID- 18809605
TI  - Late congestive heart failure after hematopoietic cell transplantation.
AB  - PURPOSE: To examine the independent roles of pre-hematopoietic cell
      transplantation (HCT) therapeutic exposures, transplantation-related
      conditioning, and comorbidities (pre- and post-HCT) in the development of late
      congestive heart failure (CHF) after HCT. METHODS: This was a nested case-control
      design. Individuals with late CHF (diagnosed >or= 1 year after HCT) were
      identified from a cohort of 2,938 1+ year survivors who underwent transplantation
      at City of Hope National Medical Center, Duarte, CA. This cohort formed the
      sampling frame for selecting controls (without CHF) matched for age and year of
      HCT, donor source (allogeneic v autologous), and length of follow-up. RESULTS:
      Sixty patients with late CHF were identified; median age at HCT was 45.3 years
      (range, 16.6 to 68.6 years); median time to CHF was 3.0 years (range, 1.03 to
      18.9 years); 68% received autologous HCT. Median ejection fraction was 36.9%
      (range, 15% to 53%). Compared with matched controls (n = 166), patients with late
      CHF received more cycles of pre-HCT chemotherapy (8.6 v 4.9 cycles; P < .01), had
      greater body mass index at HCT (28.4 v 26.2 kg/m(2); P = .01), greater lifetime
      anthracycline exposure (285.3 v 175.6 mg/m(2); P < .01), and were more likely to
      have multiple chronic comorbidities (30.0% v 13.9%; P < .01). Multivariable
      analysis revealed number of pre-HCT chemotherapy cycles (odds ratio [OR] = 1.2; P
      < .01), anthracycline dose >/= 250 mg/m(2) (OR = 3.2; P = .05), and two or more
      chronic comorbidities (OR = 4.3; P = .01) to be independently associated with
      late CHF. CONCLUSION: Pre-HCT exposure to anthracyclines and presence of
      comorbidities are primarily responsible for the risk associated with late CHF
      after HCT. Conditioning-related therapeutic exposure does not contribute
      significantly to the risk. These results form the basis for identifying high-risk
      individuals for targeted surveillance, as well as developing preventive
      strategies in the form of aggressive management of comorbidities.

PMID- 18809606
TI  - Feasibility of screening for Lynch syndrome among patients with colorectal
      cancer.
AB  - PURPOSE: Identifying individuals with Lynch syndrome (LS) is highly beneficial.
      However, it is unclear whether microsatellite instability (MSI) or
      immunohistochemistry (IHC) should be used as the screening test and whether
      screening should target all patients with colorectal cancer (CRC) or those in
      high-risk subgroups. PATIENTS AND METHODS: MSI testing and IHC for the four
      mismatch repair proteins was performed on 500 tumors from unselected patients
      with CRC. If either MSI or IHC was abnormal, complete mutation analysis for the
      mismatch repair genes was performed. RESULTS: Among the 500 patients, 18 patients
      (3.6%) had LS. All 18 patients detected with LS (100%) had MSI-high tumors; 17
      (94%) of 18 patients with LS were correctly predicted by IHC. Of the 18 probands,
      only eight patients (44%) were diagnosed at age younger than 50 years, and only
      13 patients (72%) met the revised Bethesda guidelines. When these results were
      added to data on 1,066 previously studied patients, the entire study cohort (N =
      1,566) showed an overall prevalence of 44 of 1,566 patients (2.8%; 95% CI, 2.1%
      to 3.8%) for LS. For each proband, on average, three additional family members
      carried MMR mutations. CONCLUSION: One of every 35 patients with CRC has LS, and
      each has at least three relatives with LS; all of whom can benefit from increased
      cancer surveillance. For screening, IHC is almost equally sensitive as MSI, but
      IHC is more readily available and helps to direct gene testing. Limiting tumor
      analysis to patients who fulfill Bethesda criteria would fail to identify 28% (or
      one in four) cases of LS.

PMID- 18809607
TI  - Prognostic significance of, and gene and microRNA expression signatures
      associated with, CEBPA mutations in cytogenetically normal acute myeloid leukemia
      with high-risk molecular features: a Cancer and Leukemia Group B Study.
AB  - PURPOSE: To evaluate the prognostic significance of CEBPA mutations in the
      context of established molecular markers in cytogenetically normal (CN) acute
      myeloid leukemia (AML) and gain biologic insights into leukemogenesis of the CN
      AML molecular high-risk subset (FLT3 internal tandem duplication [ITD] positive
      and/or NPM1 wild type) that has a significantly higher incidence of CEBPA
      mutations than the molecular low-risk subset (FLT3-ITD negative and NPM1
      mutated). PATIENTS AND METHODS: One hundred seventy-five adults age less than 60
      years with untreated primary CN-AML were screened before treatment for CEBPA,
      FLT3, MLL, WT1, and NPM1 mutations and BAALC and ERG expression levels. Gene and
      microRNA (miRNA) expression profiles were obtained for the CN-AML molecular high
      risk patients. RESULTS: CEBPA mutations predicted better event-free (P = .007),
      disease-free (P = .014), and overall survival (P < .001) independently of other
      molecular and clinical prognosticators. Among patients with CEBPA mutations, 91%
      were in the CN-AML molecular high-risk group. Within this group, CEBPA mutations
      predicted better event-free (P < .001), disease-free (P = .004), and overall
      survival (P = .009) independently of other molecular and clinical characteristics
      and were associated with unique gene and miRNA expression profiles. The major
      features of these profiles were upregulation of genes (eg, GATA1, ZFPM1, EPOR,
      and GFI1B) and miRNAs (ie, the miR-181 family) involved in erythroid
      differentiation and downregulation of homeobox genes. CONCLUSION: Pretreatment
      testing for CEBPA mutations identifies CN-AML patients with different outcomes,
      particularly in the molecular high-risk group, thus improving molecular risk
      based classification of this large cytogenetic subset of AML. The gene and miRNA
      expression profiling provided insights into leukemogenesis of the CN-AML
      molecular high-risk group, indicating that CEBPA mutations are associated with
      partial erythroid differentiation.

PMID- 18809608
TI  - Helper T-cell responses and clinical activity of a melanoma vaccine with multiple
      peptides from MAGE and melanocytic differentiation antigens.
AB  - PURPOSE: A phase I/II trial was performed to evaluate the safety and
      immunogenicity of a novel melanoma vaccine comprising six melanoma-associated
      peptides defined as antigenic targets for melanoma-reactive helper T cells.
      Source proteins for these peptides include MAGE proteins, MART-1/MelanA, gp100,
      and tyrosinase. PATIENTS AND METHODS: Thirty-nine patients with stage IIIB to IV
      melanoma were vaccinated with this six-peptide mixture weekly at three dose
      levels, with a preceding phase I dose escalation and subsequent random assignment
      among the dose levels. Helper T-lymphocyte responses were assessed by in vitro
      proliferation assay and delayed-type hypersensitivity skin testing. Patients with
      measurable disease were evaluated for objective clinical response by Response
      Evaluation Criteria in Solid Tumors. RESULTS: Vaccination with the helper peptide
      vaccine was well tolerated. Proliferation assays revealed induction of T-cell
      responses to the melanoma helper peptides in 81% of patients. Among 17 patients
      with measurable disease, objective clinical responses were observed in two
      patients (12%), with response durations of 1 and 3.9+ years. Durable stable
      disease was observed in two additional patients for periods of 1.8 and 4.6+
      years. CONCLUSION: Results of this study support the safety and immunogenicity of
      a vaccine comprised of six melanoma helper peptides. There is also early evidence
      of clinical activity.

PMID- 18809609
TI  - Phase II trial of weekly paclitaxel for unresectable angiosarcoma: the ANGIOTAX
      Study.
AB  - PURPOSE: The objective of this phase II trial was to assess the efficacy and
      toxicity of weekly paclitaxel for patients with metastatic or unresectable
      angiosarcoma. PATIENTS AND METHODS: Thirty patients were entered onto the study
      from April 2005 through October 2006. Paclitaxel was administered intravenously
      as a 60-minute infusion at a dose of 80 mg/m(2) on days 1, 8, and 15 of a 4-week
      cycle. The primary end point was the nonprogression rate after two cycles.
      RESULTS: The progression-free survival rates after 2 and 4 months were 74% and
      45%, respectively. With a median follow-up of 8 months, the median time to
      progression was 4 months and the median overall survival was 8 months. The
      progression-free survival rate was similar in patients pretreated with
      chemotherapy and in chemotherapy-naive patients (77% v 71%). Three patients with
      locally advanced breast angiosarcoma presented partial response, which enabled a
      secondary curative-intent surgery with complete histologic response in two cases.
      One toxic death occurred as a result of a thrombocytopenia episode. Six patients
      presented with grade 3 toxicities and one patient presented with a grade 4
      toxicity. Anemia and fatigue were the most frequently reported toxicities.
      CONCLUSION: Weekly paclitaxel at the dose schedule used in the current study was
      well tolerated and demonstrated clinical benefit.

PMID- 18809610
TI  - Novel method for benchmarking recruitment of African American cancer patients to
      clinical therapeutic trials.
AB  - PURPOSE: The National Cancer Institute (NCI) has historically evaluated the
      participation of underserved minorities within University of Pittsburgh Cancer
      Institute (UPCI) clinical trials in relation to the proportion of African
      Americans in the general population of the UPCI primary service area of Allegheny
      County (12%). This standard seemed to be unrealistically high as a result of a
      younger age distribution of African Americans within the county. METHODS: The
      proportions of African Americans within the following four separate county
      populations were compared using data from 2000 to 2004: general population;
      invasive cancer patients; invasive cancer patients diagnosed or treated at UPCI
      affiliated facilities; and patients enrolled onto UPCI's clinical therapeutic
      trials. RESULTS: Although the proportion of African Americans within the general
      population was approximately 13%, only 9.8% of patients diagnosed with invasive
      cancers were African American. Approximately 9.5% of all cancer patients
      diagnosed or treated at UPCI facilities were African American, which is
      comparable to the county-wide percentage of African American cancer patients.
      Recruitment rate of African Americans to oncology clinical trials from within the
      UPCI patient population was 7.6%. The NCI benchmark did not reflect the actual
      invasive cancer incidence rate in African American patients. By comparing the
      percentage of African Americans contributing to cancer incidence with the
      percentage of African American cancer patients treated at research-affiliated
      institutions, a more appropriate benchmark was derived. CONCLUSION: The method
      developed by UPCI is recommended as a useful mechanism for benchmarking
      recruitment of African American cancer patients to clinical therapeutic trials at
      other cancer centers.

PMID- 18809611
TI  - Autoimmune hemolytic anemia associated with ovarian cancer.

PMID- 18809612
TI  - Randomized trial of a hypnosis intervention for treatment of hot flashes among
      breast cancer survivors.
AB  - PURPOSE: Hot flashes are a significant problem for many breast cancer survivors.
      Hot flashes can cause discomfort, disrupted sleep, anxiety, and decreased quality
      of life. A well-tolerated and effective mind-body treatment for hot flashes would
      be of great value. On the basis of previous case studies, this study was
      developed to evaluate the effect of a hypnosis intervention for hot flashes.
      PATIENTS AND METHODS: Sixty female breast cancer survivors with hot flashes were
      randomly assigned to receive hypnosis intervention (five weekly sessions) or no
      treatment. Eligible patients had to have a history of primary breast cancer
      without evidence of detectable disease and 14 or more weekly hot flashes for at
      least 1 month. The major outcome measure was a bivariate construct that
      represented hot flash frequency and hot flash score, which was analyzed by a
      classic sums and differences comparison. Secondary outcome measures were self
      reports of interference of hot flashes on daily activities. RESULTS: Fifty-one
      randomly assigned women completed the study. By the end of the treatment period,
      hot flash scores (frequency x average severity) decreased 68% from baseline to
      end point in the hypnosis arm (P < .001). Significant improvements in self
      reported anxiety, depression, interference of hot flashes on daily activities,
      and sleep were observed for patients who received the hypnosis intervention (P <
      .005) in comparison to the no treatment control group. CONCLUSION: Hypnosis
      appears to reduce perceived hot flashes in breast cancer survivors and may have
      additional benefits such as reduced anxiety and depression, and improved sleep.

PMID- 18809613
TI  - Adoptive cell therapy for patients with metastatic melanoma: evaluation of
      intensive myeloablative chemoradiation preparative regimens.
AB  - PURPOSE: The two approved treatments for patients with metastatic melanoma,
      interleukin (IL)-2 and dacarbazine, mediate objective response rates of 12% to
      15%. We previously reported that adoptive cell therapy (ACT) with autologous
      antitumor lymphocytes in lymphodepleted hosts mediated objective responses in 51%
      of 35 patients. Here, we update that study and evaluate the safety and efficacy
      of two increased-intensity myeloablative lymphodepleting regimens. PATIENTS AND
      METHODS: We performed two additional sequential trials of ACT with autologous
      tumor-infiltrating lymphocytes (TIL) in patients with metastatic melanoma.
      Increasing intensity of host preparative lymphodepletion consisting of
      cyclophosphamide and fludarabine with either 2 (25 patients) or 12 Gy (25
      patients) of total-body irradiation (TBI) was administered before cell transfer.
      Objective response rates by Response Evaluation Criteria in Solid Tumors (RECIST)
      and survival were evaluated. Immunologic correlates of effective treatment were
      studied. RESULTS: Although nonmyeloablative chemotherapy alone showed an
      objective response rate of 49%, when 2 or 12 Gy of TBI was added, the response
      rates were 52% and 72% respectively. Responses were seen in all visceral sites
      including brain. There was one treatment-related death in the 93 patients. Host
      lymphodepletion was associated with increased serum levels of the lymphocyte
      homeostatic cytokines IL-7 and IL-15. Objective responses were correlated with
      the telomere length of the transferred cells. CONCLUSION: Host lymphodepletion
      followed by autologous TIL transfer and IL-2 results in objective response rates
      of 50% to 70% in patients with metastatic melanoma refractory to standard
      therapies.

PMID- 18809614
TI  - Adjuvant paclitaxel plus carboplatin compared with observation in stage IB non
      small-cell lung cancer: CALGB 9633 with the Cancer and Leukemia Group B,
      Radiation Therapy Oncology Group, and North Central Cancer Treatment Group Study
      Groups.
AB  - PURPOSE: Adjuvant chemotherapy for resected non-small-cell lung cancer (NSCLC) is
      now accepted on the basis of several randomized clinical trials (RCTs) that
      demonstrated improved survival. Although there is strong evidence that adjuvant
      chemotherapy is effective in stages II and IIIA NSCLC, its utility in stage IB
      disease is unclear. This report provides a mature analysis of Cancer and Leukemia
      Group B (CALGB) 9633, the only RCT designed specifically for stage IB NSCLC.
      PATIENTS AND METHODS: Within 4 to 8 weeks of resection, patients were randomly
      assigned to adjuvant chemotherapy or observation. Eligible patients had
      pathologically confirmed T2N0 NSCLC and had undergone lobectomy or pneumonectomy.
      Chemotherapy consisted of paclitaxel 200 mg/m(2) intravenously over 3 hours and
      carboplatin at an area under the curve dose of 6 mg/mL per minute intravenously
      over 45 to 60 minutes every 3 weeks for four cycles. The primary end point was
      overall survival. RESULTS: Three hundred-forty-four patients were randomly
      assigned. Median follow-up was 74 months. Groups were well-balanced with regard
      to demographics, histology, and extent of surgery. Grades 3 to 4 neutropenia were
      the predominant toxicity; there were no treatment-related deaths. Survival was
      not significantly different (hazard ratio [HR], 0.83; CI, 0.64 to 1.08; P = .12).
      However, exploratory analysis demonstrated a significant survival difference in
      favor of adjuvant chemotherapy for patients who had tumors > or = 4 cm in
      diameter (HR, 0.69; CI, 0.48 to 0.99; P = .043). CONCLUSION: Because a
      significant survival advantage was not observed across the entire cohort,
      adjuvant chemotherapy should not be considered standard care in stage IB NSCLC.
      Given the magnitude of observed survival differences, CALGB 9633 was underpowered
      to detect small but clinically meaningful improvements. A statistically
      significant survival advantage for patients who had tumors > or = 4 cm supports
      consideration of adjuvant paclitaxel/carboplatin for stage IB patients who have
      large tumors.

PMID- 18809615
TI  - Long-term effects of high-dose chemotherapy and radiation for relapsed and
      refractory Hodgkin's lymphoma.
AB  - PURPOSE: To evaluate the risk of late morbidity and mortality, and to assess long
      term health-related quality of life (QOL) among patients with relapsed/refractory
      Hodgkin's lymphoma (HL) after high-dose chemoradiotherapy (HDT) and autologous
      stem-cell rescue (ASCR). PATIENTS AND METHODS: From 1985 to 1998, 218 patients
      with HL were treated on HDT with ASCR salvage protocols. Of these 218, 153 (70%)
      who survived > or = 2 years after ASCR were evaluated for late morbidity and
      mortality from causes other than HL. QOL information was obtained through self
      administered questionnaires. Risk ratios (RR) were calculated to compare observed
      second malignancy (SM) rates in this cohort with expected SM rates from the
      Surveillance Epidemiology and End Results (SEER) registry. RESULTS: Median follow
      up after ASCR was 11.5 years. Among 153 patients, there were 53 deaths; 33 from
      HL and 20 from other causes. Thirteen deaths were caused by SM, with median time
      from ASCR to SM diagnosis of 9 years (range, 3 to 18 years). The RR of SM was 6.5
      (95% CI, 3.6 to 10.7) when compared with the general population, but 2.4 (95% CI,
      1.4 to 4.05) when compared with patients with HL. Global QOL of ASCR survivors
      was comparable with the general population, but for specific domains,
      respondents' scores indicated reduced functioning and worse symptoms. CONCLUSION:
      HL accounts for most deaths among patients surviving HDT and ASCR. Survivors of
      ASCR had an elevated risk of SM compared with the cancer risk in the general
      population, but when compared with patients with HL in SEER, the risk was less
      pronounced.

PMID- 18809616
TI  - Osteosarcoma in patients older than 65 years.
AB  - PURPOSE: We reviewed the outcome of osteosarcoma patients older than 65 years, an
      age group usually excluded from protocols, to determine the different clinical
      features and prognostic factors in this age group compared with younger patients.
      PATIENTS AND METHODS: Patients treated at our institute who had high-grade
      osteosarcoma and were older than 65 years were observed. RESULTS: Forty-three
      patients were eligible to be enrolled onto this study; of these, 22 were male and
      21 were female. The median age of this group was 69 years (range, 65 to 80
      years). Of the 43 patients, 29 patients had localized disease, and 14 patients
      had metastatic disease. Localizations were appendicular in 33 patients, and axial
      in 10 patients. Twenty-nine patients had a primary osteosarcoma, 13 patients
      (30%) had a sarcoma in Paget's disease, and one patient had postradiotherapy (RT)
      osteosarcoma. The median interval from onset of symptoms to diagnosis was 4
      months (range, 0 to 73 months).Thirty-two of 43 patients received surgery for a
      primary tumor. Of these, 18 patients had limb salvage, 13 patients had an
      amputation, and one patient had palliative surgery; the remaining 11 patients
      received palliative RT. Fourteen patients received chemotherapy; two deaths
      related to chemotherapy were observed. Median overall survival (OS) for all 43
      patients was 19 months (range, 3 to 229 months); 5-year OS was 22% (SE = 3%) for
      the whole group, and 45% OS for those patients with localized primary
      osteosarcoma. Multivariate analysis demonstrated that stage, volume, and surgery
      were significant prognostic factors. Insignificant prognostic factors were sex,
      type of surgery, chemotherapy, and Paget's disease. CONCLUSION: Patients older
      than 65 years with osteosarcoma have a worse prognosis compared with younger
      patients. This older age group is characterized by a longer time lapse from the
      onset of symptoms to diagnosis, more metastatic cases at diagnosis, less use of
      limb salvage, fewer patients receiving chemotherapy, and more patients excluded
      from clinical trials than a younger age group.

PMID- 18809617
TI  - Quality-of-life outcomes for adjuvant chemotherapy in early-stage non-small-cell
      lung cancer: results from a randomized trial, JBR.10.
AB  - PURPOSE: Adjuvant chemotherapy for early stage non-small-cell lung cancer (NSCLC)
      is now the standard of care, but there is little information regarding its impact
      on quality of life (QOL). We report the QOL results of JBR.10, a North American,
      intergroup, randomized trial of adjuvant cisplatin and vinorelbine compared with
      observation in patients who have completely resected, stages IB to II NSCLC.
      PATIENTS AND METHODS: QOL was assessed with the European Organisation for
      Research and Treatment of Cancer Quality of Life Questionnaire C30 and a trial
      specific checklist at baseline and at weeks 5 and 9 for those who received
      chemotherapy and at follow-up months 3, 6, 9, 12, 18, 24, 30 and 36. A 10-point
      change in QOL scores from baseline was considered clinically significant.
      RESULTS: Four hundred eighty-two patients were randomly assigned on JBR.10. A
      total of 173 patients (82% of the expected) in the observation arm and 186 (85%
      of expected) in the chemotherapy arm completed baseline QOL assessments. The two
      groups were comparable, with low global QOL scores and significant symptom
      burden, especially pain and fatigue, after thoracotomy. Changes in QOL during
      chemotherapy were relatively modest; fatigue, nausea, and vomiting worsened, but
      there was a reduction in pain and no change in global QOL. Patients in the
      observation arm showed considerable improvements in QOL by 3 months. QOL, except
      for symptoms of sensory neuropathy and hearing loss, in those treated with
      chemotherapy returned to baseline by 9 months. CONCLUSION: The findings of this
      trial indicate that the negative effects of adjuvant chemotherapy on QOL appear
      to be temporary, and that improvements (with a return to baseline function) are
      likely in most patients.

PMID- 18809618
TI  - Dominant membrane uncoupling by mutant adenine nucleotide translocase in
      mitochondrial diseases.
AB  - Adenine nucleotide translocase (Ant) is the most abundant protein on the
      mitochondrial inner membrane (MIM) primarily involved in ADP/ATP exchange. Ant
      also possesses a discrete membrane uncoupling activity. Specific mis-sense
      mutations in the human Ant1 cause autosomal dominant Progressive External
      Ophthalmoplegia (adPEO), mitochondrial myopathy and cardiomyopathy, which are
      commonly manifested by fractional mitochondrial DNA (mtDNA) deletions. It is
      currently thought that the pathogenic mutations alter substrate preference (e.g.
      ATP versus ADP) thereby dominantly disturbing adenine nucleotide homeostasis in
      mitochondria. This may interfere with mtDNA replication, consequently affecting
      mtDNA stability and oxidative phosphorylation. Here, we showed that the adPEO
      type A128P, A106D and M114P mutations in the yeast Aac2p share the following
      common dominant phenotypes: electron transport chain damage, intolerance to
      moderate over-expression, synthetic lethality with low Deltapsi(m) conditions,
      hypersensitivity to the uncoupler carbonyl cyanide m-chlorophenylhydrazone (CCCP)
      and mtDNA instability. More interestingly, the aac2(A137D) allele mimicking
      ant1(A123D) in mitochondrial myopathy and cardiomyopathy exhibits similar
      dominant phenotypes. Because Aac2(A137D) is known to completely lack transport
      activity, it is strongly argued that the dominant mitochondrial damages are not
      caused by aberrant nucleotide transport. The four pathogenic mutations occur in a
      structurally dynamic gating region on the cytosolic side. We provided direct
      evidence that the mutant alleles uncouple mitochondrial respiration. The
      pathogenic mutations likely enhance the intrinsic proton-conducting activity of
      Ant, which excessively uncouples the MIM thereby affecting energy transduction
      and mitochondrial biogenesis. mtDNA disintegration is a phenotype co-lateral to
      mitochondrial damages. These findings provide mechanistic insights into the
      pathogenesis of the Ant1-induced diseases.

PMID- 18809619
TI  - Translational bypass of nonsense mutations in zebrafish rep1, pax2.1 and lamb1
      highlights a viable therapeutic option for untreatable genetic eye disease.
AB  - The extensive molecular genetic heterogeneity seen with inherited eye disease is
      a major barrier to the development of gene-based therapeutics. The underlying
      molecular pathology in a considerable proportion of these diseases however are
      nonsense mutations leading to premature termination codons. A therapeutic
      intervention targeted at this abnormality would therefore potentially be relevant
      to a wide range of inherited eye diseases. We have taken advantage of the ability
      of aminoglycoside drugs to suppress such nonsense mutations and partially restore
      full-length, functional protein in a zebrafish model of choroideraemia
      (chm(ru848); juvenile chorio-retinal degeneration) and in two models of ocular
      coloboma (noi(tu29a) and gup(m189); congenital optic fissure closure defects). In
      vitro cell-based assays showed significant readthrough with two drugs, gentamicin
      and paromomycin, which was confirmed by western blot and in vitro prenylation
      assays. The presence of either aminoglycoside during zebrafish development in
      vivo showed remarkable prevention of mutant ocular phenotypes in each model and a
      reduction in multisystemic defects leading to a 1.5-1.7-fold increase in
      survival. We also identified a significant reduction in abnormal cell death shown
      by TUNEL assay. To test the hypothesis that optic fissure closure was apoptosis
      dependent, the anti-apoptotic agents, curcumin and zVAD-fmk, were tested in
      gup(m189) embryos. Both drugs were found to reduce the size of the coloboma,
      providing molecular evidence that cell death is required for optic fissure
      remodelling. These findings draw attention to the value of zebrafish models of
      eye disease as useful preclinical drug screening tools in studies to identify
      molecular mechanisms amenable to therapeutic intervention.

PMID- 18809620
TI  - Pectic polysaccharides from Biophytum petersianum Klotzsch, and their activation
      of macrophages and dendritic cells.
AB  - The Malian medicinal plant Biophytum petersianum Klotzsch (Oxalidaceae) is used
      as a treatment against various types of illnesses related to the immune system,
      such as joint pains, inflammations, fever, malaria, and wounds. A pectic
      polysaccharide obtained from a hot water extract of the aerial parts of B.
      petersianum has previously been reported to consist of arabinogalactans types I
      and II (AG-I and AG-II), probably linked to a rhamnogalacturonan backbone. We
      describe here further structural characteristics of the main polysaccharide
      fraction (BP1002) and fractions obtained by enzymatic degradations using endo
      alpha-d-(1-->4)-polygalacturonase (BP1002-I to IV). The results indicate that in
      addition to previously reported structures, rhamnogalacturan type II and
      xylogalacturonan areas appear to be present in the pectic polymer isolated from
      the plant. Atomic force microscopy confirmed the presence of branched structures,
      as well as a polydisperse nature. We further tested whether the BP1002 main
      fraction or the enzymatically degraded products could induce immunomodulating
      activity through stimulation of subsets of leukocytes. We found that macrophages
      and dendritic cells were activated by BP1002 fractions, while there was little
      response of T cells, B cells, and NK cells. The enzymatic treatment of the BP1002
      main fraction gave important information on the structure-activity relations. It
      seems that the presence of rhamnogalacturonan type I is important for the
      bioactivity, as the bioactivity decreases with the decreased amounts of rhamnose,
      galactose, and arabinose. The demonstration of bioactivity by the plant extracts
      might indicate the mechanisms behind the traditional medical use of the plant.

PMID- 18809621
TI  - Diabetes, abdominal adiposity, and atherogenic dyslipoproteinemia in women
      compared with men.
AB  - OBJECTIVE: To understand why atherogenic risk differs more between diabetic and
      nondiabetic women than between diabetic and nondiabetic men. RESEARCH DESIGN AND
      METHODS AND RESULTS: Measures of cardiovascular risk, body composition, and serum
      hormones from the baseline examinations of the Insulin Resistance Atherosclerosis
      Study on 524 nondiabetic women, 258 diabetic women, 421 nondiabetic men, and 220
      diabetic men were compared to detect greater adverse differences in women than in
      men. Systolic blood pressure; apolipoprotein B (apoB); total cholesterol; apoB-to
      apoA-I ratio; non-HDL cholesterol; LDL particle count, small LDL, and
      intermediate-density lipoprotein by nuclear magnetic resonance; and C-reactive
      protein exhibited significant diabetes-sex interaction (P < 0.05). ApoB exhibited
      the most significant interaction (P = 0.0005). Age- and ethnicity-adjusted apoB
      means were lower in nondiabetic women than nondiabetic men (102.4 vs. 106.8
      mg/dl, P < 0.05) but higher in diabetes (115.7 vs. 110.2 mg/dl, P < 0.01).
      Plotted against BMI, waist circumference was 6% higher and hip circumference 10%
      lower in diabetic than nondiabetic women (both P < 0.05), whereas the
      circumference measures did not differ conspicuously between diabetic and
      nondiabetic men. CONCLUSIONS: In diabetic women, an elevated level of atherogenic
      particles, as manifested by apoB and LDL particle count, which may result from
      abdominal adiposity, represents a major treatable cardiovascular risk factor.

PMID- 18809622
TI  - Improving Diabetes Care in Practice: findings from the TRANSLATE trial.
AB  - OBJECTIVE: The purpose of this study was to determine whether implementation of a
      multicomponent organizational intervention can produce significant change in
      diabetes care and outcomes in community primary care practices. RESEARCH DESIGN
      AND METHODS: This was a group-randomized, controlled clinical trial evaluating
      the practical effectiveness of a multicomponent intervention (TRANSLATE) in 24
      practices. The intervention included implementation of an electronic diabetes
      registry, visit reminders, and patient-specific physician alerts. A site
      coordinator facilitated previsit planning and a monthly review of performance
      with a local physician champion. The principle outcomes were the percentage of
      patients achieving target values for the composite of systolic blood pressure
      (SBP) <130 mmHg, LDL cholesterol <100 mg/dl, and A1C <7.0% at baseline and 12
      months. Six process measures were also followed. RESULTS: Over 24 months, 69,965
      visits from 8,405 adult patients with type 2 diabetes were recorded from 238
      health care providers in 24 practices from 17 health systems. Diabetes process
      measures increased significantly more in intervention than in control practices,
      giving net increases as follows: foot examinations 35.0% (P < 0.0.001); annual
      eye examinations 25.9% (P < 0.001); renal testing 28.5% (P < 0.001); A1C testing
      8.1%(P < 0.001); blood pressure monitoring 3.5% (P = 0.05); and LDL testing 8.6%
      (P < 0.001). Mean A1C adjusted for age, sex, and comorbidity decreased
      significantly in intervention practices (P < 0.02). At 12 months, intervention
      practices had significantly greater improvement in achieving recommended clinical
      values for SBP, A1C, and LDL than control clinics (P = 0.002). CONCLUSIONS:
      Introduction of a multicomponent organizational intervention in the primary care
      setting significantly increases the percentage of type 2 diabetic patients
      achieving recommended clinical outcomes.

PMID- 18809623
TI  - Weight-loss practices and weight-related issues among youth with type 1 or type 2
      diabetes.
AB  - OBJECTIVE: The purpose of this study was to describe the weight-loss practices
      and weight-related issues reported by youth with diabetes, according to sex and
      diabetes type. RESEARCH DESIGN AND METHODS: A total of 1,742 female and 1,615
      male youth aged 10-21 years with type 1 or type 2 diabetes completed a SEARCH for
      Diabetes in Youth study visit during which height, weight, and A1C were measured.
      A survey assessed weight-related issues and weight-loss practices. RESULTS:
      Although more common in youth with type 2 diabetes, youth with type 1 diabetes
      also reported weight-related concerns and had elevated BMI. Among youth who had
      ever tried to lose weight (n = 1,646), healthy weight-loss practices (diet
      [76.5%] and exercise [94.8%]) were the most common, whereas unhealthy practices
      (fasting [8.6%], using diet aids [7.5%], vomiting or laxative use [2.3%], and
      skipping insulin doses [4.2%]) were less common. In sex-specific multivariable
      models including age, race/ethnicity, diabetes type, BMI category, and glycemic
      control, obese females and overweight/obese males were more likely to report ever
      practicing any unhealthy weight-loss practice than normal-weight youth. These
      practices were associated with poor glycemic control for female but not male
      subjects. All unhealthy weight-loss practices except fasting were more common in
      female than in male subjects. Dieting, fasting, and using diet aids were all more
      common in youth with type 2 diabetes than in those with type 1 diabetes.
      CONCLUSIONS: Given the prevalence of overweight and obesity among youth with type
      1 or type 2 diabetes, health care professionals caring for youth with diabetes
      need to pay particular attention to identifying youth, particularly females, with
      unhealthy weight-loss practices.

PMID- 18809624
TI  - High blood pressure before and during early pregnancy is associated with an
      increased risk of gestational diabetes mellitus.
AB  - OBJECTIVE: While women with prior gestational diabetes mellitus (GDM) are more
      likely to display features of the metabolic syndrome, including hypertension, in
      the years after delivery, it is unclear whether these components are also present
      before pregnancy. We examined the relationship between blood pressure (BP)
      measured before and during early pregnancy (<20 weeks) and the risk of GDM in a
      nested case-control study. RESEARCH DESIGN AND METHODS: Case (n = 381) and
      control (n = 942) subjects were selected from a cohort of women delivering
      between 1996 and 1998 and screened for GDM between 24 and 28 weeks' gestation.
      GDM was defined by the National Diabetes Data Group criteria. BP and covariates
      data were obtained by review of the medical records. Women were categorized
      according to BP levels recommended by the American Heart Association outside of
      pregnancy: <120/80 mmHg (normal), 120-139/80-89 mmHg (prehypertension), and
      >or=140 and/or >or=90 mmHg or use of antihypertensive medications (hypertension).
      RESULTS: During early pregnancy, women with prehypertension had a small increased
      risk of GDM (odds ratio [OR] 1.56 [95% CI 1.16-2.10]), and women with
      hypertension had a twofold increased risk of GDM (2.04 [1.14-3.65]) compared with
      women with normal BP after adjusting for age, race/ethnicity, gestational week of
      BP, BMI, and parity. Similar results were seen among the subset of women with BP
      levels measured before pregnancy (1.44 [0.95-2.19] for prehypertension and 2.01
      [1.01-3.99] for hypertension). CONCLUSIONS: Clinicians should be aware that women
      presenting with hypertension may warrant early screening or intervention to
      prevent GDM.

PMID- 18809625
TI  - Is socioeconomic position related to the prevalence of metabolic syndrome?:
      influence of social class across the life course in a population-based study of
      older men.
AB  - OBJECTIVE: To examine whether adult social class and childhood social class are
      related to metabolic syndrome in later life, independent of adult behavioral
      factors. RESEARCH DESIGN AND METHODS: This was a population-based cross-sectional
      study comprising 2,968 men aged 60-79 years. RESULTS: Adult social class and
      childhood social class were both inversely related to metabolic syndrome. Mutual
      adjustment attenuated the relation of metabolic syndrome with childhood social
      class; that with adult social class was little affected. However, the relation
      with adult social class was markedly attenuated by adjustment for smoking status,
      physical activity, and alcohol consumption. High waist circumference was
      independently associated with adult social class. CONCLUSIONS: The association
      between adult social class and metabolic syndrome was largely explained by
      behavioral factors. In addition, central adiposity, a component of metabolic
      syndrome, was associated with adult social class. Focusing on healthier behaviors
      and obesity, rather than specific efforts to reduce social inequalities
      surrounding metabolic syndrome, is likely to be particularly important in
      reducing social inequalities that affect people with coronary disease.

PMID- 18809626
TI  - Plasma adiponectin does not correlate with insulin resistance and cardiometabolic
      variables in nondiabetic Asian Indian teenagers.
AB  - OBJECTIVE: The objectives of this study were to determine age- and sex-specific
      concentrations of adiponectin in Asian Indian teenagers and adults and to assess
      whether its blood levels correlated with insulin resistance and other
      cardiometabolic parameters. RESEARCH DESIGN AND METHODS: We studied 196 teenagers
      (94 boys, 102 girls) 12-18 years of age, selected from a cohort of 2,640
      individuals from a cross-sectional school-based survey in Chennai, India. For
      comparison, adiponectin and plasma insulin were measured in 84 healthy adults.
      Correlation of adiponectin with plasma levels of insulin, proinsulin, insulin
      resistance, anthropometry, and family history of diabetes were studied. RESULTS:
      Adiponectin showed a sex dimorphism, with girls having higher values (in
      microg/ml) (10.3 +/- 5.0) than boys (8.4 +/- 3.5) (P < 0.0001), and it showed a
      positive correlation with HDL cholesterol in boys only and not with other lipid
      parameters, insulin resistance, proinsulin, anthropometry, and family history of
      diabetes. In the adults, adiponectin correlated with fasting glucose and
      inversely with triglycerides. CONCLUSIONS: In Asian Indian adults and teenagers,
      adiponectin did not correlate directly with measures of insulin sensitivity,
      overweight, and other cardiometabolic variables. This was at variance with
      several reports in other populations showing an inverse association of
      adiponectin with insulin resistance, proinsulin, and BMI, suggesting ethnic
      differences in the relationship of adiponectin with insulin sensitivity. The role
      of adiponectin in relation to action of insulin needs more detailed studies in
      Asian Indians.

PMID- 18809627
TI  - Additive interaction of hyperglycemia and albuminuria on risk of ischemic stroke
      in type 2 diabetes: Hong Kong Diabetes Registry.
AB  - OBJECTIVE: The study aims to test whether biological interaction between
      hyperglycemia and albuminuria can explain the inconsistent findings from
      epidemiological studies and clinical trials about effects of hyperglycemia on
      stroke in type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 6,445 Hong
      Kong Chinese patients with type 2 diabetes and free of stroke at enrollment were
      followed up for a median of 5.37 years. Spline Cox proportional hazard regression
      was used to obtain hazard ratio curves, which were used to identify cutoff points
      of A1C and spot urinary albumin-to-creatinine ratio for increased ischemic stroke
      risk. The identified cutoff point of A1C was used to check biological interaction
      between A1C and albuminuria (micro- and macroalbuminuria). The biological
      interaction was estimated using relative excess risk due to interaction (RERI),
      attributable proportion due to interaction (AP), and synergy index. RESULTS:
      During the follow-up period, 4.45% (n = 287) of patients developed ischemic
      stroke. A1C was associated with increased hazard ratios of ischemic stroke in a
      near-linear manner except for two points-6.2 and 8.0%-where the slope between
      these two points accelerated. For A1C values <6.2%, the presence of
      micro/macroalbuminuria did not confer additional risk, while significant
      biological interaction between A1C and micro/macroalbuminuria for values >or=6.2%
      was observed (RERI 0.92, 95% CI 0.16-1.68, and AP 0.40, 0.01-0.78). CONCLUSIONS:
      A1C >or=6.2% and micro/macroalbuminuria interact to markedly increase the
      ischemic stroke risk, which explains a large proportion of risk in patients with
      type 2 diabetes harboring both risk factors.

PMID- 18809628
TI  - Zinc intake and biochemical markers of bone turnover in type 1 diabetes.
AB  - OBJECTIVE: To examine the relationship between Zn nutritive status and
      biochemical markers of bone turnover in type 1 diabetes. RESEARCH DESIGN AND
      METHODS: Serum osteocalcin, urine N-telopeptides, and dietary intake data,
      obtained by 3-day food records, were assessed for 66 individuals with type 1
      diabetes. RESULTS: Zn intake correlated with osteocalcin in the group overall (r
      = 0.48; P < 0.001) but not with N-telopeptides. Examined by sex, both Zn and
      osteocalcin correlated for men (r = 0.57; P < 0.001), but the correlation did not
      reach statistical significance for women (r = 0.34; P = 0.09). A direct-entry
      linear regression model with osteocalcin as the dependent variable was performed.
      Duration, sex, A1C, insulin use per kilogram, total calorie intake, and Zn intake
      were entered as potential independent variables. The model was statistically
      significant (R(2) = 0.32; P < 0.01). Zn intake (P < 0.001), however, was the only
      independent correlate of osteocalcin. CONCLUSIONS: This study provides evidence
      of a positive relationship between Zn intake and osteocalcin in type 1 diabetes.

PMID- 18809629
TI  - Predicting 6-year mortality risk in patients with type 2 diabetes.
AB  - OBJECTIVE: The objective of this study was to create a tool that predicts the
      risk of mortality in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS:
      This study was based on a cohort of 33,067 patients with type 2 diabetes
      identified in the Cleveland Clinic electronic health record (EHR) who were
      initially prescribed a single oral hypoglycemic agent between 1998 and 2006.
      Mortality was determined in the EHR and the Social Security Death Index. A Cox
      proportional hazards regression model was created using medication class and 20
      other predictor variables chosen for their association with mortality. A
      prediction tool was created using the Cox model coefficients. The tool was
      internally validated using repeated, random subsets of the cohort, which were not
      used to create the prediction model. RESULTS: Follow-up in the cohort ranged from
      1 day to 8.2 years (median 28.6 months), and 3,661 deaths were observed. The
      prediction tool had a concordance index (i.e., c statistic) of 0.752.
      CONCLUSIONS: We successfully created a tool that accurately predicts mortality
      risk in patients with type 2 diabetes. The incorporation of medications into
      mortality predictions in patients with type 2 diabetes should improve treatment
      decisions.

PMID- 18809630
TI  - Sociodemographic correlates of the increasing trend in prevalence of gestational
      diabetes mellitus in a large population of women between 1995 and 2005.
AB  - OBJECTIVE: Gestational diabetes mellitus (GDM) is an increasingly prevalent risk
      factor for the development of type 2 diabetes in the mother and is responsible
      for morbidity in the child. To better identify women at risk of developing GDM we
      examined sociodemographic correlates and changes in the prevalence of GDM among
      all births between 1995 and 2005 in Australia's largest state. RESEARCH DESIGN
      AND METHODS: A computerized database of all births (n = 956,738) between 1995 and
      2005 in New South Wales, Australia, was used in a multivariate logistic
      regression that examined the association between sociodemographic characteristics
      and the occurrence of GDM. RESULTS: Between 1995 and 2005, the prevalence of GDM
      increased by 45%, from 3.0 to 4.4%. Women born in South Asia had the highest
      adjusted odds ratio (OR) of any region (4.33 [95% CI 4.12-4.55]) relative to
      women born in Australia. Women living in the three lowest socioeconomic quartiles
      had higher adjusted ORs for GDM relative to women in the highest quartile (1.54
      [1.50-1.59], 1.74 [1.69-1.8], and 1.65 [1.60-1.70] for decreasing socioeconomic
      status quartiles). Increasing age was strongly associated with GDM, with women
      aged >40 years having an adjusted OR of 6.13 (95% CI 5.79-6.49) relative to women
      in their early 20s. Parity was associated with a small reduced risk. There was no
      association between smoking and GDM. CONCLUSIONS: Maternal age, socioeconomic
      position, and ethnicity are important correlates of GDM. Future culturally
      specific interventions should target prevention of GDM in these high-risk groups.

PMID- 18809631
TI  - Efficacy and safety of the dipeptidyl peptidase-4 inhibitor alogliptin in
      patients with type 2 diabetes and inadequate glycemic control: a randomized,
      double-blind, placebo-controlled study.
AB  - OBJECTIVE: To evaluate the dipeptidyl peptidase-4 (DPP-4) inhibitor alogliptin in
      drug-naive patients with inadequately controlled type 2 diabetes. RESEARCH DESIGN
      AND METHODS: This double-blind, placebo-controlled, multicenter study included
      329 patients with poorly controlled diabetes randomized to once-daily treatment
      with 12.5 mg alogliptin (n = 133), 25 mg alogliptin (n = 131), or placebo (n =
      65) for 26 weeks. Primary efficacy end point was mean change from baseline in A1C
      at the final visit. RESULTS: At week 26, mean change in A1C was significantly
      greater (P < 0.001) for 12.5 mg (-0.56%) and 25 mg (-0.59%) alogliptin than
      placebo (-0.02%). Reductions in fasting plasma glucose were also greater (P <
      0.001) in alogliptin-treated patients than in those receiving placebo. Overall,
      incidences of adverse events (67.4-70.3%) and hypoglycemia (1.5-3.0%) were
      similar across treatment groups. CONCLUSIONS: Alogliptin monotherapy was well
      tolerated and significantly improved glycemic control in patients with type 2
      diabetes, without raising the incidence of hypoglycemia.

PMID- 18809632
TI  - Virulence potential of Staphylococcus aureus strains isolated from diabetic foot
      ulcers: a new paradigm.
AB  - OBJECTIVE: The purpose of this study was to assess the virulence potential of
      Staphylococcus aureus strains isolated from diabetic foot ulcers and to
      discriminate noninfected from infected ulcers. RESEARCH DESIGN AND METHODS:
      Diabetic patients hospitalized in a diabetic foot department with a foot ulcer
      were prospectively enrolled if they had been free of antibiotic treatment over
      the previous 6 months. At admission, ulcers were classified as infected or
      noninfected on the basis of clinical examination, according to the International
      Working Group on the Diabetic Foot system. Only patients carrying S. aureus as
      the sole pathogen were included. In individuals with a grade 1 ulcer, a second
      bacterial specimen was obtained 1 month later. Using virulence genotyping
      markers, clonality tools, and an in vivo Caenorhabditis elegans model, we
      correlated the virulence of 132 S. aureus strains with grade, time of collection,
      and ulcer outcome. RESULTS: Among virulence genes, the most relevant combination
      derived from the logistic regression was the association of cap8, sea, sei, lukE,
      and hlgv (area under the curve 0.958). These markers were useful to distinguish
      noninfected (grade 1) from infected (grades 2-4) ulcers and to predict wound
      status at the follow-up. With use of the nematode model, S. aureus strains
      isolated from grade 1 ulcers were found to be significantly less virulent than
      strains from ulcers at or above grade 2 (P < 0.001). CONCLUSIONS: This study
      highlights the coexistence of two S. aureus populations on diabetic foot ulcers.
      A combination of five genes that may help distinguish colonized grade 1 from
      infected grade >or=2 wounds, predict ulcer outcome, and contribute to more
      appropriate use of antibiotics was discovered.

PMID- 18809633
TI  - Multitissue insulin resistance despite near-normoglycemic remission in Africans
      with ketosis-prone diabetes.
AB  - OBJECTIVE: To characterize insulin action in Africans with ketosis-prone diabetes
      (KPD) during remission. RESEARCH DESIGN AND METHODS: At Saint-Louis Hospital,
      Paris, France, 15 African patients with KPD with an average 10.5-month insulin
      free near-normoglycemic remission period (mean A1C 6.2%) were compared with 17
      control subjects matched for age, sex, BMI, and geographical origin. Insulin
      stimulation of glucose disposal, and insulin suppression of endogenous glucose
      production (EGP) and nonesterified fatty acids (NEFAs), was studied using a 200
      min two-step (10 mU x m(-2) body surface x min(-1) and 80 mU x m(-2) x min (-1)
      insulin infusion rates) euglycemic clamp with [6,6-(2)H(2)]glucose as the tracer.
      Early-phase insulin secretion was determined during an oral glucose tolerance
      test. RESULTS: The total glucose disposal was reduced in patients compared with
      control subjects (7.5 +/- 0.8 [mean +/- SE] vs. 10.5 +/- 0.9 mg x kg(-1) x min(
      1); P = 0.018). EGP rate was higher in patients than control subjects at baseline
      (4.0 +/- 0.3 vs. 3.0 +/- 0.1 mg x kg(-1) x min(-1); P = 0.001) and after 200-min
      insulin infusion (10 mU x m(-2) x min(-1): 1.6 +/- 0.2 vs. 0.6 +/- 0.1, P =
      0.004; 80 mU x m(-2) x min(-1): 0.3 +/- 0.1 vs. 0 mg x kg(-1) x min(-1), P =
      0.007). Basal plasma NEFA concentrations were also higher in patients (1,936.7 +/
      161.4 vs. 1,230.0 +/- 174.1 micromol/l; P = 0.002) and remained higher after 100
      min 10 mU x m(-2) x min(-1) insulin infusion (706.6 +/- 96.5 vs. 381.6 +/- 55.9
      micromol/l; P = 0.015). CONCLUSIONS: The triad hepatic, adipose tissue, and
      skeletal muscle insulin resistance is observed in patients with KPD during near
      normoglycemic remission, suggesting that KPD is a form of type 2 diabetes.

PMID- 18809634
TI  - Physician burnout in Hungary: a potential role for work-family conflict.
AB  - In a study among Hungarian physicians (N = 420), we tested the hypothesis that
      compared to men female physicians experience higher work-family conflict (WFC)
      and consequent burnout. As predicted, female physicians scored significantly
      higher on the emotional exhaustion subscale of the Maslach Burnout Inventory and
      significantly more female physicians experienced high levels of emotional
      exhaustion compared to male physicians. WFC emerged as a significant predictor of
      burnout (emotional exhaustion and depersonalization). These findings suggest a
      potential path from WFC to burnout in a scarcely researched population of
      physicians in a unique cultural setting and provide further data for cross
      cultural burnout research.

PMID- 18809635
TI  - A review on neurobiological and psychological mechanisms underlying the anti
      depressive effect of qigong exercise.
AB  - Elders with chronic medical conditions are vulnerable to depression. Mainstream
      interventions for treating their depression is however far from satisfactory
      which stimulates the interests of researchers to look for alternative therapies
      to alleviate geriatric depression. Qigong, a Chinese mindful exercise, is
      demonstrated to have anti-depressive effects. Results of our earlier studies shed
      light on the psychological mechanism underlying this effect. The neurobiological
      mechanism remains unclear. This article attempts to review extant evidence and
      suggests possible neurobiological pathways of the anti-depressive effect of
      qigong based on the neurotransmitter, neuroendocrine, and neurotropic
      perspectives. Further research to consolidate its scientific base is suggested.

PMID- 18809636
TI  - Sexually transmitted infections: impact on individuals and their relationships.
AB  - The impact of having genital herpes and genital human papilloma virus (HPV) on
      individuals and their relationships was investigated. A qualitative research
      methodology explored the lived experiences of 30 adults with genital herpes (15
      men, 15 women), and 30 adults with HPV (15 men, 15 women). This study addressed
      individuals' feelings about the impact of stigma associated with having an STI,
      the impact of having an STI on sexuality and on intimate relationships, and
      feelings surrounding the process of disclosure. Implications of the findings for
      research and clinical practice are discussed.

PMID- 18809637
TI  - Effect of participation incentives on the composition of national health surveys.
AB  - Our understanding of health attitudes and behaviors often relies on national
      surveys. This study examined how the composition of the Health Information
      National Trends Survey was influenced by participation incentives. Younger
      respondents who had had cancer were the least likely to report that a lack of
      incentive would dissuade them from participating. The group receiving no
      incentive had the smallest proportion of individuals with cancer. However, there
      was no relationship between incentive group and family history of cancer, age, or
      income. Overall, incentives appear to be a sensible way to motivate survey
      participation.

PMID- 18809638
TI  - Social capital and health: starting to make sense of the role of generalized
      trust and reciprocity.
AB  - Social capital is widely considered to influence health. It is usually defined as
      a list of components such as social networks, social participation, trust and
      reciprocity. It is trust and reciprocity that are the subjects of this article.
      The presumed relationship of each with health is rarely explained in social
      capital studies. Trust is usually treated simplistically, both conceptually and
      in relation to measurement, while reciprocity is misunderstood, under-theorized
      and rarely measured. Pathways from trust and reciprocity to better health may be
      by way of reduced stress. Clarification and valid measures are needed to progress
      studies of social capital and health.

PMID- 18809639
TI  - How do you feel? Self-esteem predicts affect, stress, social interaction, and
      symptom severity during daily life in patients with chronic illness.
AB  - Self-esteem has been demonstrated to predict health and well-being in a number of
      samples and domains using retrospective reports, but little is known about the
      effect of self-esteem in daily life. A community sample with asthma (n = 97) or
      rheumatoid arthritis (n = 31) completed a self-esteem measure and collected
      Ecological Momentary Assessment (EMA) data 5x/day for one week using a palmtop
      computer. Low self-esteem predicted more negative affect, less positive affect,
      greater stress severity, and greater symptom severity in daily life. Naturalistic
      exploration of mechanisms relating self-esteem to physiological and/or
      psychological components in illness may clarify causal relationships and inform
      theoretical models of self-care, well-being, and disease management.

PMID- 18809640
TI  - Patient empowerment in clinical genetics services.
AB  - Outcome measurement in clinical genetics is problematic because the patient
      benefits are difficult to measure. The aim in this qualitative grounded theory
      study was to develop a theoretical framework describing the patient benefits from
      using clinical genetics services. Seven focus groups and 19 interviews were
      conducted with patients, patient group representatives, and health professionals.
      Data analysis resulted in construction of a model of empowerment summarizing the
      patient benefits from using clinical genetics services. Empowerment is similar to
      the concept of perceived personal control (PPC), and a measure of PPC has been
      developed for use in evaluations of clinical genetics services. However,
      empowerment includes some benefits not captured by PPC related to empowerment of
      other at risk relatives, and future generations.

PMID- 18809641
TI  - Adolescents who intend to change multiple health behaviours choose greater
      exposure to an internet-delivered intervention.
AB  - Despite a growth of Internet-delivered interventions, exposure rates to such
      interventions are still low. In total, 35,104 adolescents participated in the E
      MOVO project: an Internet-delivered lifestyle intervention aimed at multiple
      health behaviours. By means of multilevel analyses, we demonstrated the
      relationship between intention to change behaviour and adolescents' exposure to E
      MOVO's functionalities. There was a clustering of intention to change risk taking
      behaviours in an unhealthy way and energy balance-related behaviours in a healthy
      way. This should be taken into account with the design of Internet-delivered
      interventions.

PMID- 18809642
TI  - An investigation of the effects of music on anxiety and pain perception in
      patients undergoing haemodialysis treatment.
AB  - This study aimed to investigate the effects of preferred music listening on
      anxiety and pain perception in patients undergoing haemodialysis. A two group
      experimental design was used. Sixty people diagnosed with end stage renal failure
      undergoing haemodialysis treatment participated in this study. Preferred music
      listening was applied as an intervention. Anxiety and pain were measured pre-test
      and post-test. The control group scored significantly higher in state anxiety
      than the experimental group and experienced significantly higher pain intensity
      in post-test phase. Findings provide experimental evidence to support the
      effectiveness of preferred music listening in medical settings.

PMID- 18809643
TI  - Coping with a diagnosis of C trachomatis or N gonorrhoeae: psychosocial and
      behavioral correlates.
AB  - The current study sought to add to the stress and coping literature by examining
      whether coping responses are elicited from a diagnosis of chlamydia or gonorrhea
      and, if so, whether active or passive coping responses are associated with
      particular psychological factors and prevention behaviors. Data from 259 urban,
      minority participants recently diagnosed with chlamydia or gonorrhea were
      analyzed. Results indicated that denial was associated with having more baseline
      depressive symptoms and with having more one-time partners at follow-up. Problem
      focused coping was associated with more consistent condom use at follow-up.
      Important sex and ethnicity differences were found. Intervention implications are
      discussed.

PMID- 18809644
TI  - Communicating about self and others within an online support group for women with
      breast cancer and subsequent outcomes.
AB  - Research suggests communicating too much about one's self within an online
      support group may amplify breast cancer patients' focus on their own problems and
      exacerbate negative emotions while focusing on others may have the opposite
      effects. This study explored how pronoun usage within an online support group was
      associated with subsequent mental health outcomes. There were 286 patients
      recruited into the study who filled out the pre-test and 231 completed post-tests
      four months later with survey measures including breast cancer-related concerns
      and negative emotions. Messages were analyzed using a program counting first
      person and relational pronouns. A positive relationship was found between use of
      first person pronouns and negative emotions.

PMID- 18809645
TI  - Peer crowd identification and indoor artificial UV tanning behavioral tendencies.
AB  - In this study, the relation between peer crowd identification and indoor tanning
      behavioral tendencies was examined. Participants were 174 undergraduate students
      at a large university in the USA. Results indicated peer crowd identification was
      significantly associated with indoor artificial UV tanning behavioral tendencies
      (attitudes, normative beliefs, past year use and intentions) independent of
      gender and skin type. Participants who identified with the popular peer crowd
      were at the greatest risk for indoor tanning UV exposure while identification
      with the brain crowd was protective against such behavior. The findings are
      discussed in terms of implications for future skin cancer intervention efforts.

PMID- 18809646
TI  - Applying an extended model of the theory of planned behaviour to breast self
      examination.
AB  - Few studies have examined the predictors of breast self-examination in younger
      women, where it is the primary method for the early detection of breast cancer.
      Female college students (N = 253, aged 17 to 50 years) completed items related to
      breast self-examination assessing theory of planned behaviour (TPB) constructs
      (intentions, attitude, subjective norm, perceived behavioural control), social
      influence variables of self-identity and group norm, and demographic
      characteristics. One month later, breast self-examination behaviour was assessed.
      Results supported this application of the TPB model and highlight the importance
      of group norms for strategies to increase breast self-examination in younger
      women.

PMID- 18809647
TI  - Eating disorders patients' views on their disorders and on an outpatient service:
      a qualitative study.
AB  - The objective of the study was to determine sufferers' views of outpatient
      treatment for eating disorders and provide practical recommendations for
      treatment practice. Twenty NHS outpatients participated in semi-structured
      interviews, which were subjected to thematic analysis. Respondents expressed
      ambivalence about whether their eating disorder is a way of exerting control or a
      disorder that controls them and this leads to them seeking treatment. Sufferers
      preferred a practical and sensitive approach and began to rely on treatment for
      recovery. Treatment needs to facilitate sufferers' need for control by striking a
      balance between practical and empathetic approaches that both involve patients in
      treatment decisions and give authoritative guidance.

PMID- 18809648
TI  - The interactions between physicians and dentists in managing the care of patients
      with diabetes mellitus.

PMID- 18809649
TI  - Diabetes mellitus: considerations for dentistry.
AB  - BACKGROUND: The connection between oral health and systemic health is
      bidirectional; systemic illnesses, especially metabolic disorders, affect oral
      health, and it appears that oral health may affect systemic health. METHODS: In
      this review, the authors outline the basic principles behind diabetes mellitus
      (DM) and provide some tips to help dentists manage the care of patients with DM
      better in general practice. RESULTS: DM negatively affects all microvasculature
      beds, and the soft tissues and bones supporting the teeth are susceptible. There
      is also strong evidence that the presence of periodontal disease is associated
      with increased cardiovascular morbidity in patients with DM. CONCLUSIONS: DM is a
      chronic, systemic metabolic disorder in which the orosystemic connection is
      becoming more understood. CLINICAL IMPLICATIONS: DM is a relatively common
      condition and, thus, is one that practicing dentists may encounter frequently.

PMID- 18809650
TI  - The relationship between oral health and diabetes mellitus.
AB  - BACKGROUND: The term "diabetes mellitus" describes a group of disorders
      characterized by elevated levels of glucose in the blood and abnormalities of
      carbohydrate, fat and protein metabolism. A number of oral diseases and disorders
      have been associated with diabetes mellitus, and periodontitis has been
      identified as a possible risk factor for poor metabolic control in subjects with
      diabetes. METHODS: The authors reviewed the literature to identify oral
      conditions that are affected by diabetes mellitus. They also examined the
      literature concerning periodontitis as a modifier of glycemic control. RESULTS:
      Although a number of oral disorders have been associated with diabetes mellitus,
      the data support the fact that periodontitis is a complication of diabetes.
      Patients with long-standing, poorly controlled diabetes are at risk of developing
      oral candidiasis, and the evidence indicates that periodontitis is a risk factor
      for poor glycemic control and the development of other clinical complications of
      diabetes. Evidence suggests that periodontal changes are the first clinical
      manifestation of diabetes. CONCLUSIONS: Diabetes is an important health care
      problem. The evidence suggests that oral health care providers can have a
      significant, positive effect on the oral and general health of patients with
      diabetes mellitus.

PMID- 18809651
TI  - Intranasal administration of a detoxified endotoxin vaccine protects mice against
      heterologous Gram-negative bacterial pneumonia.
AB  - When given passively or elicited actively, antibodies induced by a detoxified
      Escherichia coli J5 mutant lipopolysaccharide (J5dLPS)-group B meningococcal
      outer membrane protein (-OMP) vaccine previously protected animals from lethal
      sepsis. To assess the use of this vaccine for the treatment of Gram-negative
      bacillary pneumonia, we vaccinated mice, with or without the adjuvant CpG, by
      intranasal (i.n.) or intraperitoneal (i.p.) routes of administration. Local and
      systemic IgG levels were 2-3 logs higher following i.p. immunization compared to
      i.n. However, i.n. immunization elicited both local and systemic IgA, unlike i.p.
      administration. The addition of CpG to the vaccine, by either route of
      administration, elicited greater levels of antibody. Intranasal immunization
      protected mice against lethal heterologous Gram-negative bacillary pneumonia and
      post-immunization serum and broncho-alveolar lavage fluid mediated enhanced
      bacterial killing with peritoneal and alveolar macrophages in vitro. We conclude
      that further studies on the use of J5dLPS-OMP for the prevention of nosocomial
      pneumonia are warranted.

PMID- 18809652
TI  - Alterations in Helicobacter pylori outer membrane and outer membrane vesicle
      associated lipopolysaccharides under iron-limiting growth conditions.
AB  - Outer membrane vesicles (OMVs) shed from the gastroduodenal pathogen Helicobacter
      pylori have measurable effects on epithelial cell responses. The aim of this
      study was to determine the effect of iron availability, and its basis, on the
      extent and nature of lipopolysaccharide (LPS) produced on H. pylori OMVs and
      their parental bacterial cells. Electrophoretic, immunoblotting and structural
      analyses revealed that LPSs of bacterial cells grown under iron-limited
      conditions were notably shorter than those of bacteria and OMVs obtained from
      iron-replete conditions. Structural analysis and serological probing showed that
      LPSs of iron-replete cells and OMVs expressed O-chains of Lewis(x) with a
      terminal Lewis(y) unit, whereas Lewis(y) expression was notably reduced on
      bacteria and OMVs from iron-limiting conditions. Unlike the O-chain, the core
      oligosaccharide and lipid A moieties of iron-replete and iron-limited bacteria
      and their OMVs were similar. Quantitatively, shed OMVs from iron-replete bacteria
      were found to be LPSenriched, whereas shed OMVs from iron-limited bacteria had a
      significantly reduced content of LPS. These differences were linked to bacterial
      ATP levels. Since iron availability affects the extent and nature of LPS
      expressed by H. pylori, host iron status may contribute to H. pylori
      pathogenesis.

PMID- 18809653
TI  - Changes of midazolam pharmacokinetics in Wistar rats treated with
      lipopolysaccharide: relationship between total CYP and CYP3A2.
AB  - It has been reported that infection interferes with drug metabolism, resulting in
      changes in pharmacokinetics. In this study, we investigated the effects of
      lipopolysaccharide (LPS) on hepatic total cytochrome P450 (CYP), CYP3A2, and
      CYP2C11 contents in a transient, LPS-induced, endotoxemia model of rats. In
      addition, to assess the effects on CYP3A2 activities, the pharmacokinetics of
      midazolam (CYP3A2 substrate) and 1-OH-midazolam (metabolite of midazolam) were
      investigated. Hepatic total CYP contents were significantly low until day 3 (P <
      0.05) but returned to the control level on day 5. Hepatic CYP3A2 contents were
      significantly decreased on day 1 until day 5 (P < 0.05) but returned to the
      control level on day 7. Hepatic CYP2C11 contents were continuously low until day
      7, and lowest on day 3. The AUC of 1-OH-midazolam was significantly decreased on
      day 1 after LPS administration (P < 0.01). In conclusion, LPS (5 mg/kg) challenge
      decreased hepatic total CYP, CYP3A2, and CYP2C11 contents and also decreased the
      activities of hepatic CYP3A2. It took at least 7 days for hepatic total CYP and
      CYP3A2 to recover to control levels, and it was suggested that the changes of
      hepatic total CYP contents might correlate with those of hepatic CYP3A2 contents
      and activities. Additionally, it is shown that their changes might reflect the
      recovery process from inflammation.

PMID- 18809654
TI  - A polymer-type water-soluble peptidoglycan exhibited both Toll-like receptor 2-
      and NOD2-agonistic activities, resulting in synergistic activation of human
      monocytic cells.
AB  - Bacterial peptidoglycan (PGN) has been reported to be sensed by cell-surface Toll
      like receptor (TLR)2. On the other hand, intracellular NOD-like receptors
      recognize PGN partial structures: NOD1 and NOD2 recognize the peptide moiety
      containing diaminopimelic acid, and the muramyldipeptide (MDP) moiety,
      respectively. In this study, we examined in human monocytic THP-1 cells the pro
      inflammatory cytokine-inducing abilities of PGNs and their fragments
      enzymatically prepared from Staphylococcus epidermidis ATCC 155: a polymer-type
      water-soluble PGN possessing an intact glycan chain (SEPS) and a monomer-type PGN
      (SEPS-M). The water-soluble PGN polymer, SEPS, exhibited considerably stronger
      activities to induce pro-inflammatory cytokines than parent PGNs and the PGN
      monomer, SEPS-M. Short interference RNA targeting TLR2 and NOD2 markedly reduced
      the activities of SEPS. In the same experiments, the activities of PGNs were
      mainly reduced in TLR2-silenced cells, whereas the activities of SEPS-M as well
      as a synthetic MDP were markedly reduced in NOD2-silenced cells. Furthermore, the
      PGNs and a reference PGN from Staphylococcus aureus in combination with MDP
      synergistically induced interleukin-8 in THP-1 cells. These findings strongly
      suggested that a polymer-type water-soluble PGN fragment, SEPS, exhibits both
      TLR2-and NOD2-agonistic activities, which induced the synergistic activation of
      human monocytic cells.

PMID- 18809655
TI  - Role of actin cytoskeleton in LPS-induced NF-kappaB activation and nitric oxide
      production in murine macrophages.
AB  - Lipopolysaccharide (LPS) is a major cell wall component of Gram-negative bacteria
      and is known to cause actin cytoskeleton reorganization in a variety of cells
      including macrophages. Actin cytoskeleton dynamics influence many cell signaling
      pathways including the NF-kappaB pathway. LPS is also known to induce the
      expression of many pro-inflammatory genes via the NF-kappaB pathway. Here, we
      have investigated the role of actin cytoskeleton in LPS-induced NF-kappaB
      activation and signaling leading to the expression of iNOS and nitric oxide
      production. Using murine macrophages, we show that disruption of actin
      cytoskeleton by either cytochalasin D (CytD) or latrunculin B (LanB) does not
      affect LPS-induced NF-kappaB activation and the expression of iNOS, a NF-kappaB
      target gene. However, disruption of actin cytoskeleton caused significant
      reduction in LPS-induced nitric oxide production indicating a role of actin
      cytoskeleton in the post-translational regulation of iNOS.

PMID- 18809656
TI  - A combination of proteasome inhibitors and antibiotics prevents lethality in a
      septic shock model.
AB  - Our recent studies with lactacystin, a prototype proteasome inhibitor, have
      suggested that the proteasome is a key regulator of LPS-induced signaling
      pathways contributing to the inflammatory process. Moreover, lactacystin protects
      animals from LPS-induced shock. Therefore, we sought to identify other less toxic
      compounds that would block the chymotrypsin-like activity of the proteasome or
      LPS-induced nitric oxide (NO). After screening over 100 natural compounds (based
      on chemistry and inhibition of LPS-induced biological activities), we now report
      for the first time that quercetin, like lactacystin (the prototype proteasome
      inhibitor), and mevinolin are also inhibitors of the chymotrypsin-like activity
      of the cellular proteasome within living cells. In addition, this study also
      suggests that mevinolin and quercetin both have relatively potent anti
      inflammatory effects on LPS-treated macrophages in vitro. Interestingly, both of
      these compounds behave like lactacystin in that they block LPS-induced NO to a
      greater extent than TNF-alpha. The results of our experiments clearly suggest
      that mevinolin, in combination with the antibiotic imipenem, can provide
      protection against polymicrobial septic lethality induced by cecal-ligation and
      puncture in mice. Collectively, these studies strongly support the conclusion
      that therapeutic targeting of cellular proteasomes, in conjunction with standard
      antimicrobial therapy, may be of considerable survival benefit in the treatment
      of septic shock.

PMID- 18809657
TI  - Targeted mutagenesis in pathogenic Leptospira species: disruption of the LigB
      gene does not affect virulence in animal models of leptospirosis.
AB  - The pathogenic mechanisms of Leptospira interrogans, the causal agent of
      leptospirosis, remain largely unknown. This is mainly due to the lack of tools
      for genetically manipulating pathogenic Leptospira species. Thus, homologous
      recombination between introduced DNA and the corresponding chromosomal locus has
      never been demonstrated for this pathogen. Leptospiral immunoglobulin-like repeat
      (Lig) proteins were previously identified as putative Leptospira virulence
      factors. In this study, a ligB mutant was constructed by allelic exchange in L.
      interrogans; in this mutant a spectinomycin resistance (Spc(r)) gene replaced a
      portion of the ligB coding sequence. Gene disruption was confirmed by PCR,
      immunoblot analysis, and immunofluorescence studies. The ligB mutant did not show
      decrease virulence compared to the wild-type strain in the hamster model of
      leptospirosis. In addition, inoculation of rats with the ligB mutant induced
      persistent colonization of the kidneys. Finally, LigB was not required to mediate
      bacterial adherence to cultured cells. Taken together, our data provide the first
      evidence of site-directed homologous recombination in pathogenic Leptospira
      species. Furthermore, our data suggest that LigB does not play a major role in
      dissemination of the pathogen in the host and in the development of acute disease
      manifestations or persistent renal colonization.

PMID- 18809658
TI  - Immunogenicity of recombinant attenuated Salmonella enterica serovar Typhimurium
      vaccine strains carrying a gene that encodes Eimeria tenella antigen SO7.
AB  - Recombinant attenuated Salmonella vaccines against avian coccidiosis were
      developed to deliver Eimeria species antigens to the lymphoid tissues of chickens
      via the type 3 secretion system (T3SS) and the type 2 secretion system (T2SS) of
      Salmonella. For antigen delivery via the T3SS, the Eimeria tenella gene encoding
      sporozoite antigen SO7 was cloned downstream of the translocation domain of the
      Salmonella enterica serovar Typhimurium sopE gene in the parental pYA3868 and
      pYA3870 vectors to generate pYA4156 and pYA4157. Newly constructed T3SS vectors
      were introduced into host strain chi8879 (Delta phoP233 Delta sptP1033::xylE
      Delta asdA16), an attenuated derivative of the highly virulent UK-1 strain. The
      SopE-SO7 fusion protein was secreted by the T3SS of Salmonella. The vector
      pYA4184 was constructed for delivery of the SO7 antigen via the T2SS. The SO7
      protein was toxic to Salmonella when larger amounts were synthesized; thus, the
      synthesis of this protein was placed under the control of the lacI repressor
      gene, whose expression in turn was dependent on the amount of available arabinose
      in the medium. The pYA4184 vector was introduced into host strain chi9242 (Delta
      phoP233 Delta asdA16 Delta araBAD23 Delta relA198::araC P(BAD) lacI TT [TT is the
      T4ipIII transcription terminator]). In addition to SO7, for immunization and
      challenge studies we used the EAMZ250 antigen of Eimeria acervulina, which was
      previously shown to confer partial protection against E. acervulina challenge
      when it was delivered via the T3SS. Immunization of chickens with a combination
      of the SO7 and EAMZ250 antigens delivered via the T3SS induced superior
      protection against challenge by E. acervulina. In contrast, chickens immunized
      with SO7 that was delivered via the T2SS of Salmonella were better protected from
      challenge by E. tenella.

PMID- 18809659
TI  - Mechanisms of T-lymphocyte accumulation during experimental pleural infection
      induced by Mycobacterium bovis BCG.
AB  - Tuberculous pleurisy is a frequent extrapulmonary manifestation characterized by
      accumulation of fluid and inflammatory cells in the pleural space. Here, we
      investigated the mechanisms of T-lymphocyte accumulation in the pleural space by
      using a murine model of pleurisy induced by Mycobacterium bovis BCG.
      Intrathoracic (i.t.) injection of BCG (4.5 x 10(5) bacteria/cavity) induced
      accumulation of T lymphocytes in the pleural cavities of C57BL/6 mice. We
      observed the presence of CFU in pleural washes conducted 1, 2, 3, 7, and 15 days
      after pleurisy induction. Pretreatment with fucoidan inhibited T-lymphocyte
      accumulation at 1 day, but not at 15 days, after BCG-induced pleurisy.
      Accordingly, adoptive transfer of fluorescein isothiocyanate-labeled blood
      mononuclear cells to infected mice showed that T lymphocytes migrated into the
      pleural cavity 1 day (but not 15 days) after BCG injection. Cell-free pleural
      wash fluids recovered from mice 1 day after BCG i.t. stimulation (day 1 BCG-PW),
      but not day 7 or day 15 BCG-PW, induced in vitro T-cell transmigration, which was
      dependent on L-, P-, and E-selectins. In contrast, day 7 BCG-PW (but not day 1
      BCG-PW) induced in vitro T-lymphocyte proliferation via interleukin-2 (IL-2) and
      gamma interferon (IFN-gamma). Accordingly, in vivo IL-2 or IFN-gamma
      neutralization abolished T-lymphocyte accumulation 7 days after pleurisy
      induction. Our results demonstrate that pleural infection induced by BCG leads to
      T-lymphocyte accumulation in two waves. The acute phase depends on selectin
      mediated migration, while the second wave of T-lymphocyte accumulation seems to
      depend on a local proliferation induced by cytokines produced in situ.

PMID- 18809660
TI  - Antibodies to capsular polysaccharide and clumping factor A prevent mastitis and
      the emergence of unencapsulated and small-colony variants of Staphylococcus
      aureus in mice.
AB  - The pathogenesis of Staphylococcus aureus infections is influenced by multiple
      virulence factors that are expressed under variable conditions, and this has
      complicated the design of an effective vaccine. Clinical trials that targeted the
      capsule or clumping factor A (ClfA) failed to protect the recipients against
      staphylococcal infections. We passively immunized lactating mice with rabbit
      antibodies to S. aureus capsular polysaccharide (CP) serotype 5 (CP5) or CP8 or
      with monoclonal antibodies to ClfA. Mice immunized with antibodies to CP5 or CP8
      or with ClfA had significantly reduced tissue bacterial burdens 4 days after
      intramammary challenge with encapsulated S. aureus strains. After several
      passages in mice passively immunized with CP-specific antiserum, increasing
      numbers of stable unencapsulated variants of S. aureus were cultured from the
      infected mammary glands. Greater numbers of these unencapsulated S. aureus
      variants than of the corresponding encapsulated parental strains were
      internalized in vitro in MAC-T bovine cells. Furthermore, small-colony variants
      (SCVs) were recovered from the infected mammary glands after several passages in
      mice passively immunized with CP-specific antiserum. A combination of antibodies
      effectively sterilized mammary glands in a significant number of passively
      immunized mice. More importantly, passive immunization with antibodies to both CP
      and ClfA fully inhibited the emergence of unencapsulated "escape mutants" and
      significantly reduced the appearance of SCVs. A vaccine formulation comprising CP
      conjugates plus a surface-associated protein adhesin may be more effective than
      either antigen alone for prevention of S. aureus infections.

PMID- 18809661
TI  - The Toxoplasma gondii dense granule protein GRA7 is phosphorylated upon invasion
      and forms an unexpected association with the rhoptry proteins ROP2 and ROP4.
AB  - The obligate intracellular parasite Toxoplasma gondii infects warm-blooded
      animals throughout the world and is an opportunistic pathogen of humans. As it
      invades a host cell, Toxoplasma forms a novel organelle, the parasitophorous
      vacuole, in which it resides during its intracellular development. The parasite
      modifies the parasitophorous vacuole and its host cell with numerous proteins
      delivered from rhoptries and dense granules, which are secretory organelles
      unique to the phylum Apicomplexa. For the majority of these proteins, little is
      known other than their localization. Here we show that the dense granule protein
      GRA7 is phosphorylated but only in the presence of host cells. Within 10 min of
      invasion, GRA7 is present in strand-like structures in the host cytosol that
      contain rhoptry proteins. GRA7 strands also contain GRA1 and GRA3. Independently
      of its phosphorylation state, GRA7 associates with the rhoptry proteins ROP2 and
      ROP4 in infected host cells. This is the first report of interactions between
      proteins secreted from rhoptries and dense granules.

PMID- 18809662
TI  - Vibrio cholerae flagellins induce Toll-like receptor 5-mediated interleukin-8
      production through mitogen-activated protein kinase and NF-kappaB activation.
AB  - Vaccine reactogenicity has complicated the development of safe and effective
      live, oral cholera vaccines. Delta ctx Vibrio cholerae mutants have been shown to
      induce inflammatory diarrhea in volunteers and interleukin-8 (IL-8) production in
      cultured intestinal epithelial cells. Bacterial flagellins are known to induce IL
      8 production through Toll-like receptor 5 (TLR5). Since the V. cholerae genome
      encodes five distinct flagellin proteins, FlaA to FlaE, with homology to
      conserved TLR5 recognition regions of Salmonella FliC, we hypothesized that V.
      cholerae flagellins may contribute to IL-8 induction through TLR5 and mitogen
      activated protein kinase (MAPK) signaling. Each purified recombinant V. cholerae
      flagellin induced IL-8 production in T84 intestinal epithelial cells and also
      induced nuclear factor kappa B (NF-kappaB) activation in HEK293T/TLR5
      transfectants, which was blocked by cotransfection with a TLR5 dominant-negative
      construct, demonstrating TLR5 specificity. Supernatants derived from Delta flaAC
      and Delta flaEDB mutants induced IL-8 production in HT-29 intestinal epithelial
      cells and in HEK293T cells overexpressing TLR5, whereas Delta flaABCDE
      supernatants induced significantly less IL-8 production, demonstrating the
      contribution of multiple flagellins in IL-8 induction. NF-kappaB activation by
      Delta flaABCDE supernatants was partially restored by flaA or flaAC
      complementation. Western analysis confirmed the presence of V. cholerae
      flagellins in culture supernatants. Purified recombinant V. cholerae FlaA
      activated the MAPKs p38, c-jun N-terminal kinase (JNK), and extracellular
      regulated kinase (ERK) in T84 cells. FlaA-induced IL-8 production in T84 cells
      was inhibited by the p38 inhibitor in combination with either the JNK or ERK
      inhibitors. Collectively, these data suggest that V. cholerae flagellins are
      present in culture supernatants and can induce TLR5- and MAPK-dependent IL-8
      secretion in host cells.

PMID- 18809663
TI  - Evidence that membrane rafts are not required for the action of Clostridium
      perfringens enterotoxin.
AB  - The action of bacterial pore-forming toxins typically involves membrane rafts for
      binding, oligomerization, and/or cytotoxicity. Clostridium perfringens
      enterotoxin (CPE) is a pore-forming toxin with a unique, multistep mechanism of
      action that involves the formation of complexes containing tight junction
      proteins that include claudins and, sometimes, occludin. Using sucrose density
      gradient centrifugation, this study evaluated whether the CPE complexes reside in
      membrane rafts and what role raft microdomains play in complex formation and CPE
      induced cytotoxicity. Western blot analysis revealed that the small CPE complex
      and the CPE hexamer 1 (CH-1) complex, which is sufficient for CPE-induced
      cytotoxicity, both localize outside of rafts. The CH-2 complex was also found
      mainly in nonraft fractions, although a small pool of raft-associated CH-2
      complex that was sensitive to cholesterol depletion with methyl-beta-cyclodextrin
      (MbetaCD) was detected. Pretreatment of Caco-2 cells with MbetaCD had no
      appreciable effect on CPE-induced cytotoxicity. Claudin-4 was localized to Triton
      X-100-soluble gradient fractions of control or CPE-treated Caco-2 cells,
      indicating a raft-independent association for this CPE receptor. In contrast,
      occludin was present in raft fractions of control Caco-2 cells. Treatment with
      either MbetaCD or CPE caused most occludin molecules to shift out of lipid rafts,
      possibly due (at least in part) to the association of occludin with the CH-2
      complex. Collectively, these results suggest that CPE is a unique pore-forming
      toxin for which membrane rafts are not required for binding, oligomerization/pore
      formation, or cytotoxicity.

PMID- 18809664
TI  - Protection of wild-type and severe combined immunodeficiency mice against an
      intranasal challenge by passive immunization with monoclonal antibodies to the
      Chlamydia trachomatis mouse pneumonitis major outer membrane protein.
AB  - Monoclonal antibodies (MAbs) to the Chlamydia trachomatis mouse pneumonitis
      (MoPn) major outer membrane protein (MOMP) were characterized for their ability
      to neutralize the infectivity of this organism in vitro and in vivo. One of the
      MAbs (MoPn-23) recognizes a nonlinear epitope in the MOMP, MAb MoPn-40 binds to a
      linear epitope in the variable domain 1 (VD1), and MAb MoPn-32 recognizes the
      chlamydial lipopolysaccharide. MAb MoPn-23 neutralized 50% of the infectivity of
      Chlamydia, as measured in vitro by using HAK (Fc gammaIII(-)) and HeLa-229 (Fc
      gammaIII(+)) cells at a concentration 100 times lower than MAb MoPn-40. MAb MoPn
      32 had no neutralizing ability. In comparison to the control normal mouse
      immunoglobulin G, passive immunization of BALB/c mice with MAb MoPn-23 resulted
      in a highly significant protection against an intranasal (i.n.) challenge as
      determined by the change in body weight, the weight of the lungs, and the yield
      of Chlamydia inclusion-forming units (IFU) from the lungs. Passive immunization
      with MAb MoPn-40 resulted in a lower degree of protection, and MAb MoPn-32
      afforded no protection. MAb MoPn-23 was also tested for its ability to protect
      wild-type (WT) and severe combined immunodeficient (SCID) C.B-17 mice against an
      i.n. challenge. Protection based on total body weight, lung weight, and yield of
      Chlamydia IFU was as effective in SCID as in WT C.B-17 mice. In conclusion,
      antibodies to MOMP can protect mice against a chlamydial infection in the
      presence or absence of T and B cells.

PMID- 18809665
TI  - Characterization of two Campylobacter jejuni strains for use in volunteer
      experimental-infection studies.
AB  - The development of vaccines against Campylobacter jejuni would be facilitated by
      the ability to perform phase II challenge studies. However, molecular mimicry of
      the lipooligosaccharide (LOS) of most C. jejuni strains with human gangliosides
      presents safety concerns about the development of Guillain-Barre syndrome.
      Clinical isolates of C. jejuni that appeared to lack genes for the synthesis of
      ganglioside mimics were identified by DNA probe analyses. Two clinical isolates
      from Southeast Asia (strains BH-01-0142 and CG8421) were determined to express
      the LOS type containing N-acetyl quinovosamine. No ganglioside structures were
      observed to be present in the LOSs of these strains, and pyrosequence analyses of
      the genomes of both strains confirmed the absence of genes involved in
      ganglioside mimicry. The capsule polysaccharide (CPS) of BH-01-0142 was
      determined to be composed of galactose (Gal), 6-deoxy-ido-heptose, and, in
      smaller amounts, D-glycero-D-ido-heptose, and the CPS of CG8421 was observed to
      contain Gal, 6-deoxy-altro-heptose, N-acetyl-glucosamine, and minor amounts of 6
      deoxy-3-O-Me-altro-heptose. Both CPSs were shown to carry O-methyl
      phosphoramidate. The two genomes contained strain-specific zones, some of which
      could be traced to a plasmid origin, and both contained a large chromosomal
      insertion related to the CJEI3 element of C. jejuni RM1221. The genomes of both
      strains shared a high degree of similarity to each other and, with the exception
      of the capsule locus of CG8421, to the type strain of the HS3 serotype, TGH9011.

PMID- 18809666
TI  - Low prevalence of antibodies to preerythrocytic but not blood-stage Plasmodium
      falciparum antigens in an area of unstable malaria transmission compared to
      prevalence in an area of stable malaria transmission.
AB  - In areas where levels of transmission of Plasmodium falciparum are high and
      stable, the age-related acquisition of high-level immunoglobulin G (IgG)
      antibodies to preerythrocytic circumsporozoite protein (CSP) and liver-stage
      antigen 1 (LSA-1) has been associated with protection from clinical malaria. In
      contrast, age-related protection from malaria develops slowly or not at all in
      residents of epidemic-prone areas with unstable low levels of malaria
      transmission. We hypothesized that this suboptimal clinical and parasitological
      immunity may in part be due to reduced antibodies to CSP or LSA-1 and/or vaccine
      candidate blood-stage antigens. Frequencies and levels of IgG antibodies to CSP,
      LSA-1, thrombospondin-related adhesive protein (TRAP), apical membrane antigen 1
      (AMA-1), erythrocyte binding antigen 175 (EBA-175), and merozoite surface protein
      1 (MSP-1) were compared in 243 Kenyans living in a highland area of unstable
      transmission and 210 residents of a nearby lowland area of stable transmission.
      Levels of antibodies to CSP, LSA-1, TRAP, and AMA-1 in the oldest age group (>40
      years) in the unstable transmission area were lower than or similar to those of
      children 2 to 6 years old in the stable transmission area. Only 3.3% of
      individuals in the unstable transmission area had high levels of IgG (>2
      arbitrary units) to both CSP and LSA-1, compared to 43.3% of individuals in the
      stable transmission area. In contrast, antibody levels to and frequencies of MSP
      1 and EBA-175 were similar in adults in areas of stable and unstable malaria
      transmission. Suboptimal immunity to malaria in areas of unstable malaria
      transmission may relate in part to infrequent high-level antibodies to
      preerythrocytic antigens and AMA-1.

PMID- 18809667
TI  - Borrelia burgdorferi lacking DbpBA exhibits an early survival defect during
      experimental infection.
AB  - Several Borrelia burgdorferi genes induced under mammalian host conditions have
      been purported to be important in Lyme disease pathogenesis based on their
      binding to host structures. These genes include the dbpBA locus, whose products
      bind host decorin and glycosoaminoglycans. Recently, the dbpBA genes were
      reported to be involved in borrelial infectivity. Here we extended the previous
      observations by using culture and quantitative PCR to evaluate low- and high-dose
      murine infection by a Delta dbpBA::Gent(r) derivative of B. burgdorferi strain
      B31. The results indicate that the Delta dbpBA::Gent(r) mutant is attenuated in
      the ability to initially colonize and then persist in multiple tissues. The
      mutant exhibited a colonization defect as early as 3 days postinfection, before
      the development of an adaptive immune response, and after low-dose infection of
      SCID mice, which are deficient in adaptive immunity. These findings suggest that
      the inability to adhere to host decorin may promote clearance of B. burgdorferi,
      presumably via innate immune mechanisms. In a high-dose infection, the mutant
      disseminated to several tissues, particularly joint tissue, but it was generally
      cleared from these tissues by 3 weeks postinfection. Finally, following high-dose
      infection of SCID mice, the dbpBA mutant exhibited only a mild colonization
      defect, suggesting that the adaptive response is involved in the clearance of the
      mutant in immunocompetent mice. Taken together, these results suggest that the
      DbpBA proteins facilitate the colonization of multiple tissues by B. burgdorferi
      and are required for optimal resistance to both innate and adaptive immune
      mechanisms following needle inoculation.

PMID- 18809668
TI  - An in vivo and in vitro model of Plasmodium falciparum rosetting and
      autoagglutination mediated by varO, a group A var gene encoding a frequent
      serotype.
AB  - In the Saimiri sciureus monkey, erythrocytes infected with the varO antigenic
      variant of the Plasmodium falciparum Palo Alto 89F5 clone bind uninfected red
      blood cells (rosetting), form autoagglutinates, and have a high multiplication
      rate, three phenotypic characteristics that are associated with severe malaria in
      human patients. We report here that varO parasites express a var gene having the
      characteristics of group A var genes, and we show that the varO Duffy binding
      like 1alpha(1) (DBL1alpha(1)) domain is implicated in the rosetting of both S.
      sciureus and human erythrocytes. The soluble varO N-terminal sequence (NTS)
      DBL1alpha(1) recombinant domain, produced in a baculovirus-insect cell system,
      induced high titers of antibodies that reacted with varO-infected red blood cells
      and disrupted varO rosettes. varO parasites were culture adapted in vitro using
      human erythrocytes. They formed rosettes and autoagglutinates, and they had the
      same surface serotype and expressed the same varO gene as the monkey-propagated
      parasites. To develop an in vitro model with highly homogeneous varO parasites,
      rosette purification was combined with positive selection by panning with a varO
      NTS-DBL1alpha(1)-specific mouse monoclonal antibody. The single-variant, clonal
      parasites were used to analyze seroprevalence for varO at the village level in a
      setting where malaria is holoendemic (Dielmo, Senegal). We found 93.6% (95%
      confidence interval, 89.7 to 96.4%) seroprevalence for varO surface-reacting
      antibodies and 86.7% (95% confidence interval, 82.8 to 91.6%) seroprevalence for
      the recombinant NTS-DBL1alpha(1) domain, and virtually all permanent residents
      had seroconverted by the age of 5 years. These data imply that the varO model is
      a relevant in vivo and in vitro model for rosetting and autoagglutination that
      can be used for rational development of vaccine candidates and therapeutic
      strategies aimed at preventing malaria pathology.

PMID- 18809669
TI  - Interleukin-4-promoted T helper 2 responses enhance Nippostrongylus brasiliensis
      induced pulmonary pathology.
AB  - The role of CD4(+) T-cell interleukin-4 (IL-4) receptor alpha (IL-4Ralpha)
      expression in T helper 2 (TH2) immune responses has not been defined. To examine
      this role, we infected CD4(+) T-cell IL-4Ralpha knockout (KO) mice with the
      parasitic nematode Nippostrongylus brasiliensis, which induces strong host TH2
      responses. Although N. brasiliensis expulsion was not affected in CD4(+) T-cell
      IL-4Ralpha KO mice, the associated lung pathology was reduced. Infected CD4(+) T
      cell IL-4Ralpha KO mice showed abrogation of airway mucus production.
      Furthermore, CD4(+) T-cell IL-4Ralpha KO mouse lungs contained reduced numbers of
      lymphocytes and eosinophils. Restimulation of pulmonary region-associated T-cell
      populations showed that TH2 cytokine responses were disrupted. Secretion of IL-4,
      but not secretion of IL-13 or IL-5, from mediastinal lymph node CD4(+) T cells
      was reduced in infected CD4(+) T-cell IL-4Ralpha KO mice. Restimulation of tissue
      derived CD4(+) T cells resulted in equivalent levels of IL-4 and IL-13 on day 7
      postinfection (p.i.) in control and CD4(+) T-cell IL-4Ralpha KO mice. By day 10
      p.i. the TH2 cytokine levels had significantly declined in CD4(+) T-cell IL
      4Ralpha KO mice. Restimulation with N. brasiliensis antigen of total lung cell
      populations and populations with CD4(+) T cells depleted showed that CD4(+) T
      cells were a key TH2 cytokine source. These data demonstrated that CD4(+) T-cell
      IL-4 responsiveness facilitates eosinophil and lymphocyte recruitment, lymphocyte
      localization, and TH2 cytokine production in the allergic pathology associated
      with N. brasiliensis infections.

PMID- 18809670
TI  - A dopamine D2 receptor mutant capable of G protein-mediated signaling but
      deficient in arrestin binding.
AB  - Arrestins mediate G protein-coupled receptor desensitization, internalization,
      and signaling. Dopamine D(2) and D(3) receptors have similar structures but
      distinct characteristics of interaction with arrestins. The goals of this study
      were to compare arrestin-binding determinants in D(2) and D(3) receptors other
      than phosphorylation sites and to create a D(2) receptor that is deficient in
      arrestin binding. We first assessed the ability of purified arrestins to bind to
      glutathione transferase (GST) fusion proteins containing the receptor third
      intracellular loops (IC3). Arrestin3 bound to IC3 of both D(2) and D(3)
      receptors, with the affinity and localization of the binding site
      indistinguishable between the receptor subtypes. Mutagenesis of the GST-IC3
      fusion proteins identified an important determinant of the binding of arrestin3
      in the N-terminal region of IC3. Alanine mutations of this determinant (IYIV212
      215) in the full-length D(2) receptor generated a signaling-biased receptor with
      intact ligand binding and G-protein coupling and activation, but deficient in
      receptor-mediated arrestin3 translocation to the membrane, agonist-induced
      receptor internalization, and agonist-induced desensitization in human embryonic
      kidney 293 cells. This mutation also decreased arrestin-dependent activation of
      extracellular signal-regulated kinases. The finding that nonphosphorylated D(2)
      IC3 and D(3)-IC3 have similar affinity for arrestin is consistent with previous
      suggestions that the differential effects of D(2) and D(3) receptor activation on
      membrane translocation of arrestin and receptor internalization are due, at least
      in part, to differential phosphorylation of the receptors. In addition, these
      results imply that the sequence IYIV212-215 at the N terminus of IC3 of the D(2)
      receptor is a key element of the arrestin binding site.

PMID- 18809671
TI  - Potent activation of large-conductance Ca2+-activated K+ channels by the
      diphenylurea 1,3-bis-[2-hydroxy-5-(trifluoromethyl)phenyl]urea (NS1643) in
      pituitary tumor (GH3) cells.
AB  - 1,3-Bis-[2-hydroxy-5-(trifluoromethyl)phenyl]urea (NS1643) is reported to be an
      activator of human ether-a-go-go-related gene current. However, it remains
      unknown whether it has any effects on other types of ion channels. The effects of
      NS1643 on ion currents and membrane potential were investigated in this study.
      NS1643 stimulated Ca(2+)-activated K(+) current [I(K(Ca))] in a concentration
      dependent manner with an EC(50) value of 1.8 microM in pituitary tumor (GH(3))
      cells. In inside-out recordings, this compound applied to the intracellular side
      of the detached channels stimulated large-conductance Ca(2+)-activated K(+)
      (BK(Ca)) channels with no change in single-channel conductance. It shifted the
      activation curve of BK(Ca) channels to less depolarized voltages without altering
      the gating charge of the channels. NS1643-stimulated channel activity depended on
      intracellular Ca(2+), and mean closed time during exposure to NS1643 was reduced.
      NS1643 (3 microM) had little or no effect on peak amplitude of ether-a-go-go
      related gene-mediated K(+) current evoked by membrane hyperpolarization, although
      it increased the amplitude of late-sustained components of K(+) inward current,
      which was suppressed by paxilline but not by azimilide. NS1643 (3 microM) had no
      effect on L-type Ca(2+) current. This compound reduced repetitive firing of
      action potentials, and further application of paxilline attenuated its decrease
      in firing rate. In addition, NS1643 enhanced BK(Ca)-channel activity in human
      embryonic kidney 293T cells expressing alpha-hSlo. In summary, we clearly show
      that NS1643 interacts directly with the BK(Ca) channel to increase the amplitude
      of I(K(Ca)) in pituitary tumor (GH(3)) cells. The alpha-subunit of the channel
      may be a target for the action of this small compound.

PMID- 18809672
TI  - Imidazoquinolinone, imidazopyridine, and isoquinolindione derivatives as novel
      and potent inhibitors of the poly(ADP-ribose) polymerase (PARP): a comparison
      with standard PARP inhibitors.
AB  - We have identified three novel structures for inhibitors of the poly(ADP-ribose)
      polymerase (PARP), a nuclear enzyme activated by strand breaks in DNA and
      implicated in DNA repair, apoptosis, organ dysfunction or necrosis. 2-[4-(5
      Methyl-1H-imidazol-4-yl)-piperidin-1-yl]-4,5-dihydro-imidazo[4,5,1-i,j]quinolin-6
      one (BYK49187), 2-(4-pyridin-2-yl-phenyl)-4,5-dihydro-imidazo[4,5,1-i,j]quinolin
      6-one (BYK236864), 6-chloro-8-hydroxy-2,3-dimethyl-imidazo-[1,2-alpha]-pyridine
      (BYK20370), and 4-(1-methyl-1H-pyrrol-2-ylmethylene)-4H-isoquinolin-1,3-dione
      (BYK204165) inhibited cell-free recombinant human PARP-1 with pIC(50) values of
      8.36, 7.81, 6.40, and 7.35 (pK(i) 7.97, 7.43, 5.90, and 7.05), and murine PARP-2
      with pIC(50) values of 7.50, 7.55, 5.71, and 5.38, respectively. BYK49187,
      BYK236864, and BYK20370 displayed no selectivity for PARP-1/2, whereas BYK204165
      displayed 100-fold selectivity for PARP-1. The IC(50) values for inhibition of
      poly(ADP-ribose) synthesis in human lung epithelial A549 and cervical carcinoma
      C4I cells as well in rat cardiac myoblast H9c2 cells after PARP activation by
      H(2)O(2) were highly significantly correlated with those at cell-free PARP-1
      (r(2) = 0.89-0.96, P < 0.001) but less with those at PARP-2 (r(2) = 0.78-0.84, P
      < 0.01). The infarct size caused by coronary artery occlusion and reperfusion in
      the anesthetized rat was reduced by 22% (P < 0.05) by treatment with BYK49187 (3
      mg/kg i.v. bolus and 3 mg/kg/h i.v. during 2-h reperfusion), whereas the weaker
      PARP inhibitors, BYK236864 and BYK20370, were not cardioprotective. In
      conclusion, the imidazoquinolinone BYK49187 is a potent inhibitor of human PARP-1
      activity in cell-free and cellular assays in vitro and reduces myocardial infarct
      size in vivo. The isoquinolindione BYK204165 was found to be 100-fold more
      selective for PARP-1. Thus, both compounds might be novel and valuable tools for
      investigating PARP-1-mediated effects.

PMID- 18809673
TI  - BRD7, a novel PBAF-specific SWI/SNF subunit, is required for target gene
      activation and repression in embryonic stem cells.
AB  - The composition of chromatin-remodeling complexes dictates how these enzymes
      control transcriptional programs and cellular identity. In the present study we
      investigated the composition of SWI/SNF complexes in embryonic stem cells (ESCs).
      In contrast to differentiated cells, ESCs have a biased incorporation of certain
      paralogous SWI/SNF subunits with low levels of BRM, BAF170, and ARID1B. Upon
      differentiation, the expression of these subunits increases, resulting in a
      higher diversity of compositionally distinct SWI/SNF enzymes. We also identified
      BRD7 as a novel component of the Polybromo-associated BRG1-associated factor
      (PBAF) complex in both ESCs and differentiated cells. Using short hairpin RNA
      mediated depletion of BRG1, we showed that SWI/SNF can function as both a
      repressor and an activator in pluripotent cells, regulating expression of
      developmental modifiers and signaling components such as Nodal, ADAMTS1, BMI-1,
      CRABP1, and thyroid releasing hormone. Knockdown studies of PBAF-specific BRD7
      and of a signature subunit within the BAF complex, ARID1A, showed that these two
      subcomplexes affect SWI/SNF target genes differentially, in some cases even
      antagonistically. This may be due to their different biochemical properties.
      Finally we examined the role of SWI/SNF in regulating its target genes during
      differentiation. We found that SWI/SNF affects recruitment of components of the
      preinitiation complex in a promoter-specific manner to modulate transcription
      positively or negatively. Taken together, our results provide insight into the
      function of compositionally diverse SWI/SNF enzymes that underlie their inherent
      gene-specific mode of action.

PMID- 18809674
TI  - Overexpression of glucose-6-phosphate dehydrogenase extends the life span of
      Drosophila melanogaster.
AB  - The redox state of tissues tends to become progressively more prooxidizing during
      the aging process. The hypothesis tested in this study was that enhancement of
      reductive capacity by overexpression of glucose-6-phosphate dehydrogenase (G6PD),
      a key enzyme for NADPH biosynthesis, could protect against oxidative stress and
      extend the life span of transgenic Drosophila melanogaster. Overexpression of
      G6PD was achieved by combining a UAS-G6PD responder transgene at one of four
      independent loci with either a broad expression (armadillo-GAL4, Tubulin-GAL4,
      C23-GAL4, and da-GAL4) or a neuronal driver (D42-GAL4 and Appl-GAL4). The mean
      life spans of G6PD overexpressor flies were extended, in comparison with driver
      and responder controls, as follows: armadillo-GAL4 (up to 38%), Tubulin-GAL4 (up
      to 29%), C23-GAL4 (up to 27%), da-GAL4 (up to 24%), D42-GAL4 (up to 18%), and
      Appl-GAL4 (up to 16%). The G6PD enzymatic activity was increased, as were the
      levels of NADPH, NADH, and the GSH/GSSG ratio. Resistance to experimental
      oxidative stress was enhanced. Furthermore, metabolic rates and fertility were
      essentially the same in G6PD overexpressors and control flies. Collectively, the
      results demonstrate that enhancement of the NADPH biosynthetic capability can
      extend the life span of a relatively long-lived strain of flies, which supports
      the oxidative stress hypothesis of aging.

PMID- 18809675
TI  - Albumin-conjugated C34 peptide HIV-1 fusion inhibitor: equipotent to C34 and T-20
      in vitro with sustained activity in SCID-hu Thy/Liv mice.
AB  - Entry inhibitors of human immunodeficiency virus, type 1 (HIV-1) have been the
      focus of much recent research. C34, a potent fusion inhibitor derived from the
      HR2 region of gp41, was engineered into a 1:1 human serum albumin conjugate
      through stable covalent attachment of a maleimido-C34 analog onto cysteine 34 of
      albumin. This bioconjugate, PC-1505, was designed to require less frequent dosing
      and less peptide than T-20 and was assessed for its antifusogenic activity both
      in vitro and in vivo in the SCID-hu Thy/Liv mouse model. PC-1505 was essentially
      equipotent to the original C34 peptide and to T-20 in vitro. In HIV-1-infected
      SCID-hu Thy/Liv mice, T-20 lost activity with infrequent dosing, whereas the
      antiviral potency of PC-1505 was sustained, and PC-1505 was active against T-20
      resistant ("DIV") virus with a G36D substitution in gp41. The in vivo results are
      the direct result of a significantly improved pharmacokinetic profile for the C34
      peptide following albumin conjugation. Contrary to previous reports that the gp41
      NHR trimer is poorly accessible to C34 fused to protein cargoes of increasing
      size (Hamburger, A. E., Kim, S., Welch, B. D., and Kay, M. S. (2005) J. Biol.
      Chem. 280, 12567-12572), these results are the first demonstration of the
      capacity for a large, endogenous serum protein to gain unobstructed access to the
      transient gp41 intermediates that exist during the HIV fusion process, and it
      supports further development of albumin conjugation as a promising approach to
      inhibit HIV-1 entry.

PMID- 18809676
TI  - Biophysical characterization of the interaction between hepatic glucokinase and
      its regulatory protein: impact of physiological and pharmacological effectors.
AB  - Glucokinase (GK) is a key enzyme of glucose metabolism in liver and pancreatic
      beta-cells, and small molecule activators of GK (GKAs) are under evaluation for
      the treatment of type 2 diabetes. In liver, GK activity is controlled by the GK
      regulatory protein (GKRP), which forms an inhibitory complex with the enzyme.
      Here, we performed isothermal titration calorimetry and surface plasmon resonance
      experiments to characterize GK-GKRP binding and to study the influence that
      physiological and pharmacological effectors of GK have on the protein-protein
      interaction. In the presence of fructose-6-phosphate, GK-GKRP complex formation
      displayed a strong entropic driving force opposed by a large positive enthalpy; a
      negative change in heat capacity was observed (Kd = 45 nm, DeltaH = 15.6
      kcal/mol, TDeltaS = 25.7 kcal/mol, DeltaCp = -354 cal mol(-1) K(-1)). With k(off)
      = 1.3 x 10(-2) s(-1), the complex dissociated quickly. The thermodynamic profile
      suggested a largely hydrophobic interaction. In addition, effects of pH and
      buffer demonstrated the coupled uptake of one proton and indicated an ionic
      contribution to binding. Glucose decreased the binding affinity between GK and
      GKRP. This decrease was potentiated by an ATP analogue. Prototypical GKAs of the
      amino-heteroaryl-amide type bound to GK in a glucose-dependent manner and
      impaired the association of GK with GKRP. This mechanism might contribute to the
      antidiabetic effects of GKAs.

PMID- 18809677
TI  - Modulation of the rate of peptidyl transfer on the ribosome by the nature of
      substrates.
AB  - The ribosome catalyzes peptide bond formation between peptidyl-tRNA in the P site
      and aminoacyl-tRNA in the A site. Here, we show that the nature of the C-terminal
      amino acid residue in the P-site peptidyl-tRNA strongly affects the rate of
      peptidyl transfer. Depending on the C-terminal amino acid of the peptidyl-tRNA,
      the rate of reaction with the small A-site substrate puromycin varied between 100
      and 0.14 s(-1), regardless of the tRNA identity. The reactivity decreased in the
      order Lys = Arg > Ala > Ser > Phe = Val > Asp >> Pro, with Pro being by far the
      slowest. However, when Phe-tRNA(Phe) was used as A-site substrate, the rate of
      peptide bond formation with any peptidyl-tRNA was approximately 7 s(-1), which
      corresponds to the rate of binding of Phe-tRNA(Phe) to the A site
      (accommodation). Because accommodation is rate-limiting for peptide bond
      formation, the reaction rate is uniform for all peptidyl-tRNAs, regardless of the
      variations of the intrinsic chemical reactivities. On the other hand, the 50-fold
      increase in the reaction rate for peptidyl-tRNA ending with Pro suggests that
      full-length aminoacyl-tRNA in the A site greatly accelerates peptide bond
      formation.

PMID- 18809678
TI  - An unusual RNA recognition motif acts as a scaffold for multiple proteins in the
      pre-mRNA retention and splicing complex.
AB  - The yeast pre-mRNA retention and splicing complex counteracts the escape of
      unspliced pre-mRNAs from the nucleus and activates splicing of a subset of Mer1p
      dependent genes. A homologous complex is present in activated human spliceosomes.
      In many components of the spliceosome, RNA recognition motifs (RRMs) serve as
      versatile protein-RNA or protein-protein interaction platforms. Here, we show
      that in the retention and splicing complex, an atypical RRM of the Snu17p (small
      nuclear ribonucleoprotein-associated protein 17) subunit acts as a scaffold that
      organizes the other two constituents, Bud13p (bud site selection 13) and Pml1p
      (pre-mRNA leakage 1). GST pull-down experiments and size exclusion chromatography
      revealed that Snu17p constitutes the central platform of the complex, whereas
      Bud13p and Pml1p do not interact with each other. Fluorimetric structure probing
      showed the entire Bud13p and the N-terminal third of Pml1p to be natively
      disordered in isolation. Mutational analysis and tryptophan fluorescence
      confirmed that a conserved tryptophan-containing motif in the C terminus of
      Bud13p binds to the core RRM of Snu17p, whereas a different interaction surface
      encompassing a C-terminal extension of the Snu17p RRM is required to bind an N
      terminal peptide of Pml1p. Isothermal titration calorimetry revealed 1:1
      interaction stoichiometries, large negative binding entropies, and dissociation
      constants in the low nanomolar and micromolar ranges for the Snu17p-Bud13p and
      the Snu17p-Pml1p interactions, respectively. Our results demonstrate that the
      noncanonical Snu17p RRM concomitantly binds multiple ligand proteins via short,
      intrinsically unstructured peptide epitopes and thereby acts as a platform that
      displays functional modules of the ligands, such as a forkhead-associated domain
      of Pml1p and a conserved polylysine motif of Bud13p.

PMID- 18809679
TI  - Filamin B mediates ICAM-1-driven leukocyte transendothelial migration.
AB  - During inflammation, the endothelium mediates rolling and firm adhesion of
      activated leukocytes. Integrin-mediated adhesion to endothelial ligands of the Ig
      superfamily induces intracellular signaling in endothelial cells, which promotes
      leukocyte transendothelial migration. We identified the actin cross-linking
      molecule filamin B as a novel binding partner for intracellular adhesion molecule
      1 (ICAM-1). Immune precipitation as well as laser scanning confocal microscopy
      confirmed the specific interaction and co-localization of endogenous filamin B
      with ICAM-1. Importantly, clustering of ICAM-1 promotes the ICAM-1-filamin B
      interaction. To investigate the functional consequences of filamin B binding to
      ICAM-1, we used small interfering RNA to reduce filamin B expression in ICAM-1
      GFP expressing HeLa cells. We found that filamin B is required for the lateral
      mobility of ICAM-1 and for ICAM-1-induced transmigration of leukocytes. Reducing
      filamin B expression in primary human endothelial cells resulted in reduced
      recruitment of ICAM-1 to endothelial docking structures, reduced firm adhesion of
      the leukocytes to the endothelium, and inhibition of transendothelial migration.
      In conclusion, this study identifies filamin B as a molecular linker that
      mediates ICAM-1-driven transendothelial migration.

PMID- 18809680
TI  - A delta-catenin signaling pathway leading to dendritic protrusions.
AB  - Delta-catenin is a synaptic adherens junction protein pivotally positioned to
      serve as a signaling sensor and integrator. Expression of delta-catenin induces
      filopodia-like protrusions in neurons. Here we show that the small GTPases of the
      Rho family act coordinately as downstream effectors of delta-catenin. A dominant
      negative Rac prevented delta-catenin-induced protrusions, and Cdc42 activity was
      dramatically increased by delta-catenin expression. A kinase dead LIMK (LIM
      kinase) and a mutant Cofilin also prevented delta-catenin-induced protrusions. To
      link the effects of delta-catenin to a physiological pathway, we noted that (S)
      3,5-dihydroxyphenylglycine (DHPG) activation of metabotropic glutamate receptors
      induced dendritic protrusions that are very similar to those induced by delta
      catenin. Furthermore, delta-catenin RNA-mediated interference can block the
      induction of dendritic protrusions by DHPG. Interestingly, DHPG dissociated PSD
      95 and N-cadherin from the delta-catenin complex, increased the association of
      delta-catenin with Cortactin, and induced the phosphorylation of delta-catenin
      within the sites that bind to these protein partners.

PMID- 18809681
TI  - Molecular dissection of the mechanisms of substrate recognition and F-actin
      mediated activation of cofilin-phosphatase Slingshot-1.
AB  - Slingshot-1 (SSH1), a member of a dual-specificity protein phosphatase family,
      regulates actin dynamics by dephosphorylating and reactivating cofilin, an actin
      depolymerizing factor. SSH1 has the SSH family-specific, N-terminal, noncatalytic
      (SSH-N) domain, consisting of the A and B subdomains. SSH1 is activated by
      binding to actin filaments. In this study, we examined the mechanisms of SSH1
      substrate recognition of phospho-cofilin (P-cofilin) and SSH1 activation by F
      actin. We found that P-cofilin binds to a phosphatase-inactive mutant, SSH1(CS),
      in which the catalytic Cys-393 is replaced by Ser. Using a series of deletion
      mutants, we provided evidence that both the phosphatase (P) domain and the
      adjacent B domain are indispensable for P-cofilin binding of SSH1(CS) and cofilin
      phosphatase activity of SSH1. In contrast, the A domain is required for the F
      actin-mediated activation of SSH1, but not for P-cofilin binding or basal cofilin
      phosphatase activity. The P domain alone is sufficient for the phosphatase
      activity toward p-nitrophenyl phosphate (pNPP), indicating that the SSH-N domain
      is not essential for the basal phosphatase activity of SSH1. Addition of F-actin
      increased the cofilin-phosphatase activity of SSH1 more than 1200-fold, but the
      pNPP-phosphatase activity only 2.2-fold, which suggests that F-actin principally
      affects the cofilin-specific phosphatase activity of SSH1. When expressed in
      cultured cells, SSH1, but not its mutant deleted of SSH-N, accumulated in the
      rear of the lamellipodium. Together, these findings suggest that the conserved
      SSH-N domain plays critical roles in P-cofilin recognition, F-actin-mediated
      activation, and subcellular localization of SSH1.

PMID- 18809682
TI  - Interaction between the C termini of Alg13 and Alg14 mediates formation of the
      active UDP-N-acetylglucosamine transferase complex.
AB  - The second step of eukaryotic N-linked glycosylation in endoplasmic reticulum is
      catalyzed by an UDP-N-acetylglucosamine transferase that is comprised of two
      subunits, Alg13 and Alg14. The interaction between Alg13 and 14 is crucial for
      UDP-GlcNAc transferase activity, so formation of the Alg13/14 complex is likely
      to play a key role in the regulation of N-glycosylation. Using a combination of
      bioinformatics and molecular biological methods, we have undertaken a functional
      analysis of yeast Alg13 and Alg14 proteins to elucidate the mechanism of their
      interaction. Our mutational studies demonstrated that a short C-terminal alpha
      helix of Alg13 is required for interaction with Alg14 and for enzyme activity.
      Electrostatic surface views of the modeled Alg13/14 complex suggest the presence
      of a hydrophobic cleft in Alg14 that provides a pocket for the Alg13 C-terminal
      alpha-helix. Co-immunoprecipitation assays confirmed the C-terminal three amino
      acids of Alg14 are required for maintaining the integrity of Alg13/Alg14 complex,
      and this depends on their hydrophobicity. Modeling studies place these three
      Alg14 residues at the entrance of the hydrophobic-binding pocket, suggesting
      their role in the stabilization of the interaction between the C termini of Alg13
      and Alg14. Together, these results demonstrate that formation of this hetero
      oligomeric complex is mediated by a short C-terminal alpha-helix of Alg13 in
      cooperation with the last three amino acids of Alg14. In addition, deletion of
      the N-terminal beta-strand of Alg13 caused the destruction of protein, indicating
      the structural importance of this region in protein stability.

PMID- 18809683
TI  - Actin pedestal formation by enteropathogenic Escherichia coli is regulated by
      IQGAP1, calcium, and calmodulin.
AB  - During infection, enteropathogenic Escherichia coli (EPEC) injects effector
      proteins into the host cell to manipulate the actin cytoskeleton and promote
      formation of actin pedestals. IQGAP1 is a multidomain protein that participates
      in numerous cellular functions, including Rac1/Cdc42 and Ca(2+)/calmodulin
      signaling and actin polymerization. Here we report that IQGAP1, Ca(2+), and
      calmodulin modulate actin pedestal formation by EPEC. Infection with EPEC
      promotes both the interaction of IQGAP1 with calmodulin and the localization of
      IQGAP1 and calmodulin to actin pedestals while reducing the interaction of IQGAP1
      with Rac1 and Cdc42. IQGAP1-null fibroblasts display a reduced polymerization of
      actin in response to EPEC. In addition, antagonism of calmodulin or chelation of
      intracellular Ca(2+) reduces EPEC-dependent actin polymerization. Furthermore,
      IQGAP1 specifically interacts with Tir in vitro and in cells. Together these data
      identify IQGAP1, Ca(2+), and calmodulin as a novel signaling complex regulating
      actin pedestal formation by EPEC.

PMID- 18809684
TI  - G9a and HP1 couple histone and DNA methylation to TNFalpha transcription
      silencing during endotoxin tolerance.
AB  - TNFalpha gene expression is silenced in the endotoxin tolerant phenotype that
      develops in blood leukocytes after the initial activation phase of severe
      systemic inflammation or sepsis. The silencing phase can be mimicked in vitro by
      LPS stimulation. We reported that the TNFalpha transcription is disrupted in
      endotoxin tolerant THP-1 human promonocyte due to changes in transcription factor
      binding and enrichment with histone H3 dimethylated on lysine 9 (H3K9). Here we
      show that the TNFalpha promoter is hypermethylated during endotoxin tolerance and
      that H3K9 methylation and DNA methylation interact to silence TNFalpha
      expression. Chromatin immunoprecipitation and RNA interference analysis
      demonstrated that, in tolerant cells, TNFalpha promoter is bound by the H3K9
      histone methyltransferase G9a which dimethylates H3K9 and creates a platform for
      HP1 binding, leading to the recruitment of the DNA methyltransferase Dnmt3a/b and
      an increase in promoter CpG methylation. Knockdown of HP1 resulted in a decreased
      Dnmt3a/b binding, sustained G9a binding, and a modest increase in TNFalpha
      transcription, but had no effect on H3K9 dimethylation. In contrast, G9a
      knockdown-disrupted promoter silencing and restored TNFalpha transcription in
      tolerant cells. This correlated with a near loss of H3K9 dimethylation, a
      significant decrease in HP1 and Dnmt3a/b binding and promoter CpG methylation.
      Our results demonstrate a central role for G9a in this process and suggest that
      histone methylation and DNA methylation cooperatively interact via HP1 to silence
      TNFalpha expression during endotoxin tolerance and may have implication for
      proinflammatory gene silencing associated with severe systemic inflammation.

PMID- 18809685
TI  - Snake phospholipase A2 neurotoxins enter neurons, bind specifically to
      mitochondria, and open their transition pores.
AB  - Snake presynaptic neurotoxins with phospholipase A(2) activity are potent
      inducers of paralysis through inhibition of the neuromuscular junction. These
      neurotoxins were recently shown to induce exocytosis of synaptic vesicles
      following the production of lysophospholipids and fatty acids and a sustained
      influx of Ca(2+) from the medium. Here, we show that these toxins are able to
      penetrate spinal cord motor neurons and cerebellar granule neurons and
      selectively bind to mitochondria. As a result of this interaction, mitochondria
      depolarize and undergo a profound shape change from elongated and spaghetti-like
      to round and swollen. We show that snake presynaptic phospholipase A(2)
      neurotoxins facilitate opening of the mitochondrial permeability transition pore,
      an inner membrane high-conductance channel. The relative potency of the snake
      neurotoxins was similar for the permeability transition pore opening and for the
      phospholipid hydrolysis activities, suggesting a causal relationship, which is
      also supported by the effect of phospholipid hydrolysis products,
      lysophospholipids and fatty acids, on mitochondrial pore opening. These findings
      contribute to define the cellular events that lead to intoxication of nerve
      terminals by these snake neurotoxins and suggest that mitochondrial impairment is
      an important determinant of their toxicity.

PMID- 18809686
TI  - Design of a conformationally defined and proteolytically stable circular mimetic
      of brain-derived neurotrophic factor.
AB  - Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family
      of neurotrophic factors. BDNF has long been recognized to have potential for the
      treatment of a variety of human neurodegenerative diseases. However, clinical
      trials with recombinant BDNF have yet to yield success, leading to the suggestion
      that alternative means of harnessing BDNF actions for therapeutic use may be
      required. Here we describe an approach to create low molecular weight peptides
      that, like BDNF, promote neuronal survival. The peptides were designed to mimic a
      cationic tripeptide sequence in loop 4 of BDNF shown in previous studies to
      contribute to the binding of BDNF to the common neurotrophin receptor p75NTR. The
      best of these peptides, the cyclic pentapeptide 2 (cyclo(-D-Pro-Ala-Lys-Arg-)),
      despite being of low molecular weight (Mr 580), was found to be an effective
      promoter of the survival of embryonic chick dorsal root ganglion sensory neurons
      in vitro (maximal survival, 68 +/- 3% of neurons supported by BDNF). Pentapeptide
      2 did not affect the phosphorylation of either TrkB (the receptor tyrosine kinase
      for BDNF) or the downstream signaling molecule MAPK, indicating that its
      mechanism of neuronal survival action is independent of TrkB. NMR studies reveal
      that pentapeptide 2 adopts a well defined backbone conformation in solution.
      Furthermore, pentapeptide 2 was found to be effectively resistant to proteolysis
      when incubated in a solution of rat plasma in vitro. These properties of
      pentapeptide 2 (low molecular weight, appropriate pharmacological actions, a well
      defined solution conformation, and proteolytic stability) render it worthy of
      further investigation, either as a template for the further design of neuronal
      survival promoting agents or as a lead compound with therapeutic potential in its
      own right.

PMID- 18809687
TI  - Two active forms of Zymomonas mobilis levansucrase. An ordered microfibril
      structure of the enzyme promotes levan polymerization.
AB  - Fructansucrases, members of glycoside hydrolase family 68, catalyze both sucrose
      hydrolysis and the polymerization of fructose to beta-d-fructofuranose polymers.
      The resulting fructan polymers are distinguished by the nature of the glycosidic
      bond: inulin (beta-(2-1)-fructofuranose) and levan (beta-(2-6)-fructofuranose).
      In this study we demonstrate that Zymomonas mobilis levansucrase exists in two
      active forms, depending on the pH and ionic strength. At pH values above 7.0, the
      enzyme is mainly a dimer, whereas at pH values below 6.0, the protein forms well
      ordered microfibrils that precipitate out of the solution. These two forms are
      readily interchangeable simply by changing the pH. Surprisingly the manner in
      which the enzyme is arranged strongly affects its product specificity and kinetic
      properties. At pH values above 7.0, the activity of the enzyme as a dimer is
      mainly sucrose hydrolysis and the synthesis of short fructosaccharides (degree of
      polymerization, 3). At pH values below 6.0, in its microfibril form, the enzyme
      catalyzes almost exclusively the synthesis of levan (a degree of polymerization
      greater than 20,000). This difference in product specificity appears to depend on
      the form of the enzyme, dimer versus microfibril, and not directly on the pH.
      Images made by negative stain transmission electron microscopy reveal that the
      enzyme forms a very ordered structure of long fibrils that appear to be composed
      of repeating rings of six to eight protein units. A single amino acid replacement
      of H296R abolished the ability of the enzyme to form microfibrils with organized
      fibril networks and to synthesize levan at pH 6.0.

PMID- 18809688
TI  - Molecular dynamics simulations of the Apo-, Holo-, and acyl-forms of Escherichia
      coli acyl carrier protein.
AB  - Acyl carrier protein (ACP) is an essential co-factor protein in fatty acid
      biosynthesis that shuttles covalently bound fatty acyl intermediates in its
      hydrophobic pocket to various enzyme partners. To characterize acyl chain-ACP
      interactions and their influence on enzyme interactions, we performed 19
      molecular dynamics (MD) simulations of Escherichia coli apo-, holo-, and acyl
      ACPs. The simulations were started with the acyl chain in either a solvent
      exposed or a buried conformation. All four short-chain (< or = C10) and one long
      chain (C16) unbiased acyl-ACP MD simulation show the transition of the solvent
      exposed acyl chain into the hydrophobic pocket of ACP, revealing its pathway of
      acyl chain binding. Although the acyl chain resides inside the pocket, Thr-39 and
      Glu-60 at the entrance stabilize the phosphopantetheine linker through hydrogen
      bonding. Comparisons of the different ACP forms indicate that the loop region
      between helices II and III and the prosthetic linker may aid in substrate
      recognition by enzymes of fatty acid synthase systems. The MD simulations
      consistently show that the hydrophobic binding pocket of ACP is best suited to
      accommodate an octanoyl group and is capable of adjusting in size to accommodate
      chain lengths as long as decanoic acid. The simulations also reveal a second,
      novel binding mode of the acyl chains inside the hydrophobic binding pocket
      directed toward helix I. This study provides a detailed dynamic picture of acyl
      ACPs that is in excellent agreement with available experimental data and,
      thereby, provides a new understanding of enzyme-ACP interactions.

PMID- 18809689
TI  - Is the receptivity of substance abuse prevention programming affected by
      students' perceptions of the instructor?
AB  - Drawing on the elaboration likelihood model of persuasive communication, the
      authors examine the impact of the perceptions of the instructor or source on
      students' receptivity to a new substance abuse prevention curriculum. Using
      survey data from a cohort of students participating in the Adolescent Substance
      Abuse Prevention Study, the authors use structural equation modeling to determine
      the effects of the perceptions students have of their program instructor on
      measures of the targeted program mediators and the use of cigarettes, alcohol,
      and marijuana. They test these instructor effects after each component of a two
      part curriculum is administered (during the seventh and ninth grades). They find
      that the perceptions of the instructor significantly affect refusal,
      communication and decision-making skills, normative beliefs, perceived
      consequences of use, and substance use. The authors discuss the implications of
      these findings for school-based prevention programming and indications for
      further research.

PMID- 18809690
TI  - Breath alcohol level and plasma amino acids: a comparison between older and
      younger chronic alcohol-dependent patients.
AB  - AIM: The aim of the present study is to examine the distribution of plasma
      excitatory and inhibitory amino acids, according to the age and current breath
      alcohol levels (BrAl+/-), of alcohol-dependent patients. PARTICIPANTS AND
      METHODS: 78 alcohol-dependent patients (mean age=46.2+/-11 years,
      men/women=54/24) were clinically tested, including the determination of the major
      excitatory as well as inhibitory amino acids. The independent variables were
      gender, age and current alcohol consumption measured with the breath alcohol
      level (BrAl+/-status). RESULTS: In comparison to BrAl negatives, BrAl positives
      had higher plasma levels of glutamic acid (P=0.01) and proline (P=0.026), and
      lower levels of aminobutyric acid (P=0.002), serine (P=0.031) and urea (P=0.01).
      In the BrAl positives, no age effect was found related to the plasma amino acids.
      In contrast, the BrAl negatives displayed age-related differences. The older
      (>or=50 years) BrAl negative patients had higher plasma levels of cystine,
      tyrosine, citrulline and urea, and lower histidine levels, compared to the
      younger group (<50 years). In general, differences in plasma levels of certain
      amino acids were dependent on gender, BrAl status, age and biochemical markers
      (GGT, MCV) of alcohol abuse. CONCLUSIONS: Abstaining patients (BrAl-/) display
      age-related differences in AAs' distribution, while active drinking (BrAl+/)
      seems to even out those differences, underpinning the hypothesis that drinking
      mimics changes seen with advanced age.

PMID- 18809691
TI  - Medulloblastoma: new insights into biology and treatment.

PMID- 18809692
TI  - Changing colours.

PMID- 18809693
TI  - Drug use in acute meningococcal disease.

PMID- 18809694
TI  - How to use: a rating score to diagnose attention deficit hyperactivity disorder.

PMID- 18809695
TI  - Autism spectrum disorders, SIGN.

PMID- 18809697
TI  - Herpes complex.

PMID- 18809698
TI  - Disseminated gonococcal infection in a homosexual man diagnosed by nucleic acid
      amplification testing from a skin lesion swab.
AB  - Disseminated gonococcal infection (DGI) often presents a diagnostic challenge.
      Through the novel application of molecular technology, a case is presented that
      suggests how the diagnostic sensitivity for this systemic complication of
      gonococcal infection can be improved. In a typical case of DGI seen in a
      homosexual man in whom all mucosal and blood specimens were culture negative,
      nucleic acid amplification testing (NAAT) helped to confirm the diagnosis. Both
      throat and skin lesion specimens tested positive for gonococcal DNA and this was
      confirmed with a supplementary porA pseudogene NAAT. The use of adjuvant NAAT
      assessment is recommended as part of the diagnostic work-up for suspected DGI
      cases.

PMID- 18809700
TI  - Publishing the evidence for children's medicines.

PMID- 18809701
TI  - Medical abbreviations: writing little and communicating less.

PMID- 18809702
TI  - Cystic fibrosis and the transition to adult health services.

PMID- 18809705
TI  - Getting it wrong.

PMID- 18809706
TI  - What does this study test, and why?

PMID- 18809707
TI  - Response to the article by Baird et al.

PMID- 18809711
TI  - Increased IL-12 inhibits B cells' differentiation to germinal center cells and
      promotes differentiation to short-lived plasmablasts.
AB  - B cells activated by antigen in T cell-dependent immune responses can become
      short-lived plasma cells, which remain in the spleen, or germinal center-derived
      memory or plasma cells, which show evidence of affinity maturation and, in the
      case of plasma cells, migrate to the bone marrow. We show that this cell fate
      decision can be governed by the cytokine environment engendered by activated
      dendritic cells (DCs). DCs from mice lacking the Fc receptor gamma chain
      exhibited an activated phenotype in vitro. They secreted more of the
      proinflammatory cytokine IL-12, which led to the preferential generation of short
      lived splenic plasma cells, with ensuing low affinity antibodies and a diminished
      recall response. Understanding the factors that regulate antigen-activated B cell
      differentiation and memory cell formation has implications for both antibody
      mediated autoimmune disease and protective antibody responses.

PMID- 18809712
TI  - The p110 delta of PI3K plays a critical role in NK cell terminal maturation and
      cytokine/chemokine generation.
AB  - Phosphatidylinositol 3-kinases (PI3Ks) play a critical role in regulating B cell
      receptor- and T cell receptor-mediated signaling. However, their role in natural
      killer (NK) cell development and functions is not well understood. Using mice
      expressing p110 delta(D910A), a catalytically inactive p110 delta, we show that
      these mice had reduced NK cellularity, defective Ly49C and Ly49I NK subset
      maturation, and decreased CD27(High) NK numbers. p110 delta inactivation
      marginally impaired NK-mediated cytotoxicity against tumor cells in vitro and in
      vivo. However, NKG2D, Ly49D, and NK1.1 receptor-mediated cytokine and chemokine
      generation by NK cells was severely affected in these mice. Further, p110
      delta(D910A/D910A) NK cell-mediated antiviral responses through natural
      cytotoxicity receptor 1 were reduced. Analysis of signaling events demonstrates
      that p110 delta(D910A/D910A) NK cells had a reduced c-Jun N-terminal kinase 1/2
      phosphorylation in response to NKG2D-mediated activation. These results reveal a
      previously unrecognized role of PI3K-p110 delta in NK cell development and
      effector functions.

PMID- 18809713
TI  - Dissecting T cell lineage relationships by cellular barcoding.
AB  - T cells, as well as other cell types, are composed of phenotypically and
      functionally distinct subsets. However, for many of these populations it is
      unclear whether they develop from common or separate progenitors. To address such
      issues, we developed a novel approach, termed cellular barcoding, that allows the
      dissection of lineage relationships. We demonstrate that the labeling of cells
      with unique identifiers coupled to a microarray-based detection system can be
      used to analyze family relationships between the progeny of such cells. To
      exemplify the potential of this technique, we studied migration patterns of
      families of antigen-specific CD8(+) T cells in vivo. We demonstrate that progeny
      of individual T cells rapidly seed independent lymph nodes and that antigen
      specific CD8(+) T cells present at different effector sites are largely derived
      from a common pool of precursors. These data show how locally primed T cells
      disperse and provide a technology for kinship analysis with wider utility.

PMID- 18809714
TI  - Inhibition of dendritic cell differentiation and accumulation of myeloid-derived
      suppressor cells in cancer is regulated by S100A9 protein.
AB  - Accumulation of myeloid-derived suppressor cells (MDSCs) associated with
      inhibition of dendritic cell (DC) differentiation is one of the major
      immunological abnormalities in cancer and leads to suppression of antitumor
      immune responses. The molecular mechanism of this phenomenon remains unclear. We
      report here that STAT3-inducible up-regulation of the myeloid-related protein
      S100A9 enhances MDSC production in cancer. Mice lacking this protein mounted
      potent antitumor immune responses and rejected implanted tumors. This effect was
      reversed by administration of wild-type MDSCs from tumor-bearing mice to S100A9
      null mice. Overexpression of S100A9 in cultured embryonic stem cells or
      transgenic mice inhibited the differentiation of DCs and macrophages and induced
      accumulation of MDSCs. This study demonstrates that tumor-induced up-regulation
      of S100A9 protein is critically important for accumulation of MDSCs and reveals a
      novel molecular mechanism of immunological abnormalities in cancer.

PMID- 18809715
TI  - Transient high glucose causes persistent epigenetic changes and altered gene
      expression during subsequent normoglycemia.
AB  - The current goal of diabetes therapy is to reduce time-averaged mean levels of
      glycemia, measured as HbA1c, to prevent diabetic complications. However, HbA1c
      only explains <25% of the variation in risk of developing complications. Because
      HbA1c does not correlate with glycemic variability when adjusted for mean blood
      glucose, we hypothesized that transient spikes of hyperglycemia may be an HbA1c
      independent risk factor for diabetic complications. We show that transient
      hyperglycemia induces long-lasting activating epigenetic changes in the promoter
      of the nuclear factor kappaB (NF-kappaB) subunit p65 in aortic endothelial cells
      both in vitro and in nondiabetic mice, which cause increased p65 gene expression.
      Both the epigenetic changes and the gene expression changes persist for at least
      6 d of subsequent normal glycemia, as do NF-kappaB-induced increases in monocyte
      chemoattractant protein 1 and vascular cell adhesion molecule 1 expression.
      Hyperglycemia-induced epigenetic changes and increased p65 expression are
      prevented by reducing mitochondrial superoxide production or superoxide-induced
      alpha-oxoaldehydes. These results highlight the dramatic and long-lasting effects
      that short-term hyperglycemic spikes can have on vascular cells and suggest that
      transient spikes of hyperglycemia may be an HbA1c-independent risk factor for
      diabetic complications.

PMID- 18809716
TI  - TSC-mTOR maintains quiescence and function of hematopoietic stem cells by
      repressing mitochondrial biogenesis and reactive oxygen species.
AB  - The tuberous sclerosis complex (TSC)-mammalian target of rapamycin (mTOR) pathway
      is a key regulator of cellular metabolism. We used conditional deletion of Tsc1
      to address how quiescence is associated with the function of hematopoietic stem
      cells (HSCs). We demonstrate that Tsc1 deletion in the HSCs drives them from
      quiescence into rapid cycling, with increased mitochondrial biogenesis and
      elevated levels of reactive oxygen species (ROS). Importantly, this deletion
      dramatically reduced both hematopoiesis and self-renewal of HSCs, as revealed by
      serial and competitive bone marrow transplantation. In vivo treatment with an ROS
      antagonist restored HSC numbers and functions. These data demonstrated that the
      TSC-mTOR pathway maintains the quiescence and function of HSCs by repressing ROS
      production. The detrimental effect of up-regulated ROS in metabolically active
      HSCs may explain the well-documented association between quiescence and the
      "stemness" of HSCs.

PMID- 18809717
TI  - Chemerin reveals its chimeric nature.
AB  - Chemerin is a proinflammatory plasma protein that binds to the GPCR
      ChemR23/CMKLR1 on macrophages and plasmacytoid dendritic cells, and promotes
      chemotaxis. An orphan GPCR, CCRL2, has now been identified as an additional
      receptor for chemerin, providing a unique mechanism by which chemerin enhances
      inflammation. Furthermore, because recent data shows that chemerin-derived
      peptides possess antiinflammatory properties, chemerin may be involved in both
      the initiation and resolution of inflammation.

PMID- 18809718
TI  - Kris DeMali: fixed on cell adhesion. Interview by Ruth Williams.

PMID- 18809719
TI  - Gene associations: true romance or chance meeting in a nuclear neighborhood?
AB  - Many recent studies have raised interest in the nuclear associations of
      coregulated genes from different chromosomes, often evoking interpretations of
      gene-gene interactions, communication, and even "romance." However, in some
      cases, the associations may be indirect and infrequent and may reflect the
      segregation of active and inactive genes into different nuclear compartments. The
      study by Brown et al. (see p. 1083 of this issue) reports that the apparent
      association of erythroid genes is not a direct interaction nor colocalization to
      one tiny transcription factory but arises as a result of the known clustering of
      many active genes with larger splicing factor-rich speckles (a.k.a., SC35-defined
      domains). This clustering appears largely stochastic but is impacted by the
      chromosomal neighborhood of the gene as well as its transcriptional status. The
      study adds a new twist by examining the same gene in a foreign chromosomal
      context, providing evidence that this impacts a gene's propensity to form gene
      domain (or apparent gene-gene) associations within nuclei.

PMID- 18809720
TI  - Consensus nomenclature for the human ArfGAP domain-containing proteins.
AB  - At the FASEB summer research conference on "Arf Family GTPases", held in Il
      Ciocco, Italy in June, 2007, it became evident to researchers that our
      understanding of the family of Arf GTPase activating proteins (ArfGAPs) has grown
      exponentially in recent years. A common nomenclature for these genes and proteins
      will facilitate discovery of biological functions and possible connections to
      pathogenesis. Nearly 100 researchers were contacted to generate a consensus
      nomenclature for human ArfGAPs. This article describes the resulting consensus
      nomenclature and provides a brief description of each of the 10 subfamilies of 31
      human genes encoding proteins containing the ArfGAP domain.

PMID- 18809721
TI  - Direct role of dynein motor in stable kinetochore-microtubule attachment,
      orientation, and alignment.
AB  - Cytoplasmic dynein has been implicated in diverse mitotic functions, several
      involving its association with kinetochores. Much of the supporting evidence
      comes from inhibition of dynein regulatory factors. To obtain direct insight into
      kinetochore dynein function, we expressed a series of dynein tail fragments,
      which we find displace motor-containing dynein heavy chain (HC) from kinetochores
      without affecting other subunits, regulatory factors, or microtubule binding
      proteins. Cells with bipolar mitotic spindles progress to late prometaphase
      metaphase at normal rates. However, the dynein tail, dynactin, Mad1, and BubR1
      persist at the aligned kinetochores, which is consistent with a role for dynein
      in self-removal and spindle assembly checkpoint inactivation. Kinetochore pairs
      also show evidence of misorientation relative to the spindle equator and abnormal
      oscillatory behavior. Further, kinetochore microtubule bundles are severely
      destabilized at reduced temperatures. Dynein HC RNAi and injection of anti-dynein
      antibody in MG132-arrested metaphase cells produced similar effects. These
      results identify a novel function for the dynein motor in stable microtubule
      attachment and maintenance of kinetochore orientation during metaphase chromosome
      alignment.

PMID- 18809722
TI  - Lis1 and Ndel1 influence the timing of nuclear envelope breakdown in neural stem
      cells.
AB  - Lis1 and Ndel1 are essential for animal development. They interact directly with
      one another and with cytoplasmic dynein. The developing brain is especially
      sensitive to reduced Lis1 or Ndel1 levels, as both proteins influence spindle
      orientation, neural cell fate decisions, and neuronal migration. We report here
      that Lis1 and Ndel1 reduction in a mitotic cell line impairs prophase nuclear
      envelope (NE) invagination (PNEI). This dynein-dependent process facilitates NE
      breakdown (NEBD) and occurs before the establishment of the bipolar spindle.
      Ndel1 phosphorylation is important for this function, regulating binding to both
      Lis1 and dynein. Prophase cells in the ventricular zone (VZ) of embryonic day
      13.5 Lis1(+/-) mouse brains show reduced PNEI, and the ratio of prophase to
      prometaphase cells is increased, suggesting an NEBD delay. Moreover, prophase
      cells in the VZ contain elevated levels of Ndel1 phosphorylated at a key cdk5
      site. Our data suggest that a delay in NEBD in the VZ could contribute to
      developmental defects associated with Lis1-Ndel1 disruption.

PMID- 18809723
TI  - Ryk cooperates with Frizzled 7 to promote Wnt11-mediated endocytosis and is
      essential for Xenopus laevis convergent extension movements.
AB  - The single-pass transmembrane protein Ryk (atypical receptor related tyrosine
      kinase) functions as a Wnt receptor. However, Ryk's correlation with Wnt/Frizzled
      (Fz) signaling is poorly understood. Here, we report that Ryk regulates Xenopus
      laevis convergent extension (CE) movements via the beta-arrestin 2 (betaarr2)
      dependent endocytic process triggered by noncanonical Wnt signaling. During X.
      laevis gastrulation, betaarr2-mediated endocytosis of Fz7 and dishevelled
      (Dvl/Dsh) actually occurs in the dorsal marginal zone tissues, which actively
      participate in noncanonical Wnt signaling. Noncanonical Wnt11/Fz7-mediated
      endocytosis of Dsh requires the cell-membrane protein Ryk. Ryk interacts with
      both Wnt11 and betaarr2, cooperates with Fz7 to mediate Wnt11-stimulated
      endocytosis of Dsh, and signals the noncanonical Wnt pathway in CE movements.
      Conversely, depletion of Ryk and Wnt11 prevents Dsh endocytosis in dorsal
      marginal zone tissues. Our study suggests that Ryk functions as an essential
      regulator for noncanonical Wnt/Fz-mediated endocytosis in the regulation of X.
      laevis CE movements.

PMID- 18809724
TI  - Association between active genes occurs at nuclear speckles and is modulated by
      chromatin environment.
AB  - Genes on different chromosomes can be spatially associated in the nucleus in
      several transcriptional and regulatory situations; however, the functional
      significance of such associations remains unclear. Using human erythropoiesis as
      a model, we show that five cotranscribed genes, which are found on four different
      chromosomes, associate with each other at significant but variable frequencies.
      Those genes most frequently in association lie in decondensed stretches of
      chromatin. By replacing the mouse alpha-globin gene cluster in situ with its
      human counterpart, we demonstrate a direct effect of the regional chromatin
      environment on the frequency of association, whereas nascent transcription from
      the human alpha-globin gene appears unaffected. We see no evidence that
      cotranscribed erythroid genes associate at shared transcription foci, but we do
      see stochastic clustering of active genes around common nuclear SC35-enriched
      speckles (hence the apparent nonrandom association between genes). Thus,
      association between active genes may result from their location on decondensed
      chromatin that enables clustering around common nuclear speckles.

PMID- 18809725
TI  - Ero1L, a thiol oxidase, is required for Notch signaling through cysteine bridge
      formation of the Lin12-Notch repeats in Drosophila melanogaster.
AB  - Notch-mediated cell-cell communication regulates numerous developmental processes
      and cell fate decisions. Through a mosaic genetic screen in Drosophila
      melanogaster, we identified a role in Notch signaling for a conserved thiol
      oxidase, endoplasmic reticulum (ER) oxidoreductin 1-like (Ero1L). Although Ero1L
      is reported to play a widespread role in protein folding in yeast, in flies Ero1L
      mutant clones show specific defects in lateral inhibition and inductive
      signaling, two characteristic processes regulated by Notch signaling. Ero1L
      mutant cells accumulate high levels of Notch protein in the ER and induce the
      unfolded protein response, suggesting that Notch is misfolded and fails to be
      exported from the ER. Biochemical assays demonstrate that Ero1L is required for
      formation of disulfide bonds of three Lin12-Notch repeats (LNRs) present in the
      extracellular domain of Notch. These LNRs are unique to the Notch family of
      proteins. Therefore, we have uncovered an unexpected requirement for Ero1L in the
      maturation of the Notch receptor.

PMID- 18809726
TI  - Efficient termination of vacuolar Rab GTPase signaling requires coordinated
      action by a GAP and a protein kinase.
AB  - Rab guanosine triphosphatases (GTPases) are pivotal regulators of membrane
      identity and dynamics, but the in vivo pathways that control Rab signaling are
      poorly defined. Here, we show that the GTPase-activating protein Gyp7 inactivates
      the yeast vacuole Rab Ypt7 in vivo. To efficiently terminate Ypt7 signaling, Gyp7
      requires downstream assistance from an inhibitory casein kinase I, Yck3. Yck3
      mediates phosphorylation of at least two Ypt7 signaling targets: a tether, the
      Vps-C/homotypic fusion and vacuole protein sorting (HOPS) subunit Vps41, and a
      SNARE, Vam3. Phosphorylation of both substrates is opposed by Ypt7-guanosine
      triphosphate (GTP). We further demonstrate that Ypt7 binds not one but two Vps
      C/HOPS subunits: Vps39, a putative Ypt7 nucleotide exchange factor, and Vps41.
      Gyp7-stimulated GTP hydrolysis on Ypt7 therefore appears to trigger both passive
      termination of Ypt7 signaling and active kinase-mediated inhibition of Ypt7's
      downstream targets. We propose that signal propagation through the Ypt7 pathway
      is controlled by integrated feedback and feed-forward loops. In this model, Yck3
      enforces a requirement for the activated Rab in docking and fusion.

PMID- 18809727
TI  - NCAM induces CaMKIIalpha-mediated RPTPalpha phosphorylation to enhance its
      catalytic activity and neurite outgrowth.
AB  - Receptor protein tyrosine phosphatase alpha (RPTPalpha) phosphatase activity is
      required for intracellular signaling cascades that are activated in motile cells
      and growing neurites. Little is known, however, about mechanisms that coordinate
      RPTPalpha activity with cell behavior. We show that clustering of neural cell
      adhesion molecule (NCAM) at the cell surface is coupled to an increase in serine
      phosphorylation and phosphatase activity of RPTPalpha. NCAM associates with T-
      and L-type voltage-dependent Ca(2+) channels, and NCAM clustering at the cell
      surface results in Ca(2+) influx via these channels and activation of NCAM
      associated calmodulin-dependent protein kinase IIalpha (CaMKIIalpha). Clustering
      of NCAM promotes its redistribution to lipid rafts and the formation of a NCAM
      RPTPalpha-CaMKIIalpha complex, resulting in serine phosphorylation of RPTPalpha
      by CaMKIIalpha. Overexpression of RPTPalpha with mutated Ser180 and Ser204
      interferes with NCAM-induced neurite outgrowth, which indicates that neurite
      extension depends on NCAM-induced up-regulation of RPTPalpha activity. Thus, we
      reveal a novel function for a cell adhesion molecule in coordination of cell
      behavior with intracellular phosphatase activity.

PMID- 18809729
TI  - Does non-invasive ventilation associated with chest physiotherapy improve outcome
      after lung resection?
AB  - A best evidence topic was constructed according to a structured protocol. The
      question addressed was whether the use of non-invasive ventilation (NIV)
      associated with chest physiotherapy (CPT) is effective in preventing respiratory
      complications in patients undergoing lung resection surgery. Of the 172 papers
      found using a report search, five presented the best evidence to answer the
      clinical question. The authors, journal, date and country of publication, study
      type, group studied, relevant outcomes and results of these papers are given. We
      conclude that, on the whole, the five studies were all in favor of NIV as an
      adjuvant to CPT for improving outcome after lung resection surgery. Indeed, the
      interest and benefit has been shown not only in the treatment of postoperative
      acute respiratory failure, but also in the prevention and treatment of
      respiratory complications (atelectasis, pneumonia and bronchial congestion).
      Hence, current evidence shows NIV associated with acute CPT management to be safe
      and effective in reducing postoperative complications and in improving patient
      recovery, thus enhancing the choice of available medical care and bettering
      outcome in lung resection surgery.

PMID- 18809728
TI  - The WAVE2 complex regulates T cell receptor signaling to integrins via Abl- and
      CrkL-C3G-mediated activation of Rap1.
AB  - WAVE2 regulates T cell receptor (TCR)-stimulated actin cytoskeletal dynamics
      leading to both integrin clustering and affinity maturation. Although WAVE2
      mediates integrin affinity maturation by recruiting vinculin and talin to the
      immunological synapse in an Arp2/3-dependent manner, the mechanism by which it
      regulates integrin clustering is unclear. We show that the Abl tyrosine kinase
      associates with the WAVE2 complex and TCR ligation induces WAVE2-dependent
      membrane recruitment of Abl. Furthermore, we show that WAVE2 regulates TCR
      mediated activation of the integrin regulatory guanosine triphosphatase Rap1 via
      the recruitment and activation of the CrkL-C3G exchange complex. Moreover, we
      demonstrate that although Abl does not regulate the recruitment of CrkL-C3G into
      the membrane, it does affect the tyrosine phosphorylation of C3G, which is
      required for its guanine nucleotide exchange factor activity toward Rap1. This
      signaling node regulates not only TCR-stimulated integrin clustering but also
      affinity maturation. These findings identify a previously unknown mechanism by
      which the WAVE2 complex regulates TCR signaling to Rap1 and integrin activation.

PMID- 18809730
TI  - Interindividual variation in relative CYP1A2/3A4 phenotype influences
      susceptibility of clozapine oxidation to cytochrome P450-specific inhibition in
      human hepatic microsomes.
AB  - The atypical antipsychotic drug clozapine (CLZ) is effective in a substantial
      number of patients who exhibit treatment-resistance to conventional agents.
      CYP1A2 is generally considered to be the major enzyme involved in the
      biotransformation of CLZ to its N-demethylated (norCLZ) and N-oxygenated (CLZ N
      oxide) metabolites in liver, but several studies have also implicated CYP3A4. The
      present study assessed the interplay between these cytochrome P450s (P450s) in
      CLZ biotransformation in a panel of hepatic microsomal fractions from 14
      individuals. The relative activity of P450s 1A2 and 3A4 in microsomes was found
      to be a major determinant of the relative susceptibility of norCLZ formation to
      inhibition by the P450-selective inhibitors fluvoxamine and ketoconazole. In
      contrast, the activity of CYP3A4 alone was correlated with the susceptibility of
      CLZ N-oxide formation to inhibition by these agents. These findings suggest that
      both P450s may be dominant CLZ oxidases in patients and that the relative
      activities of these enzymes may determine clearance pathways. In vivo assessment
      of CYP1A2 and CYP3A4 activities, perhaps by phenotyping approaches, could assist
      the optimization of CLZ dosage and minimize pharmacokinetic interactions with
      coadministered drugs.

PMID- 18809731
TI  - An assessment of drug-drug interactions: the effect of desvenlafaxine and
      duloxetine on the pharmacokinetics of the CYP2D6 probe desipramine in healthy
      subjects.
AB  - A number of antidepressants inhibit the activity of the cytochrome P450 2D6
      enzyme system, which can lead to drug-drug interactions. Based on its metabolic
      profile, desvenlafaxine, administered as desvenlafaxine succinate, a new
      serotonin-norepinephrine reuptake inhibitor, is not expected to have an impact on
      activity of CYP2D6. This single-center, randomized, open-label, four-period,
      crossover study was undertaken to evaluate the effect of multiple doses of
      desvenlafaxine (100 mg/day, twice the recommended therapeutic dose for major
      depressive disorder in the United States) and duloxetine (30 mg b.i.d.) on the
      pharmacokinetics (PK) of a single dose of desipramine (50 mg). A single dose of
      desipramine was given first to assess its PK. Desvenlafaxine or duloxetine was
      then administered, in a crossover design, so that steady-state levels were
      achieved; a single dose of desipramine was then coadministered. The geometric
      least-square mean ratios (coadministration versus desipramine alone) for area
      under the plasma concentration versus time curve (AUC) and peak plasma
      concentrations (C(max)) of desipramine and 2-hydroxydesipramine were compared
      using analysis of variance. Relative to desipramine alone, increases in AUC and
      C(max) of desipramine associated with duloxetine administration (122 and 63%,
      respectively) were significantly greater than those associated with
      desvenlafaxine (22 and 19%, respectively; P < 0.001). Duloxetine coadministered
      with desipramine was also associated with a decrease in 2-hydroxydesipramine
      C(max) that was significant compared with the small increase seen with
      desvenlafaxine and desipramine (-24 versus 9%; P < 0.001); the difference between
      changes in 2-hydroxydesipramine AUC did not reach statistical significance (P =
      0.054). Overall, desvenlafaxine had a minimal impact on the PK of desipramine
      compared with duloxetine, suggesting a lower risk for CYP2D6-mediated drug
      interactions.

PMID- 18809732
TI  - Design, data analysis, and simulation of in vitro drug transport kinetic
      experiments using a mechanistic in vitro model.
AB  - The use of in vitro data for quantitative predictions of transporter-mediated
      elimination in vivo requires an accurate estimation of the transporter Michaelis
      Menten parameters, V(max) and K(m), as a first step. Therefore, the experimental
      conditions of in vitro studies used to assess hepatic uptake transport were
      optimized regarding active transport processes, nonspecific binding, and passive
      diffusion (P(dif)). A mechanistic model was developed to analyze and accurately
      describe these active and passive processes. This two-compartmental model was
      parameterized to account for nonspecific binding, bidirectional passive
      diffusion, and active uptake processes based on the physiology of the cells. The
      model was used to estimate kinetic parameters of in vitro transport data from
      organic anion-transporting peptide model substrates (e.g., cholecystokinin
      octapeptide deltorphin II, fexofenadine, and pitavastatin). Data analysis by this
      mechanistic model significantly improved the accuracy and precision in all
      derived parameters [mean coefficient of variations (CVs) for V(max) and K(m) were
      19 and 23%, respectively] compared with the conventional kinetic method of
      transport data analysis (mean CVs were 58 and 115%, respectively, using this
      method). Furthermore, permeability was found to be highly temperature-dependent
      in Chinese hamster ovary (CHO) control cells and artificial membranes (parallel
      artificial membrane permeability assay). Whereas for some compounds
      (taurocholate, estrone-3-sulfate, and propranolol) the effect was moderate (1.5-6
      fold higher permeability at 37 degrees C compared with that at 4 degrees C), for
      fexofenadine a 16-fold higher passive permeability was seen at 37 degrees C.
      Therefore, P(dif) was better predicted if it was evaluated under the same
      experimental conditions as V(max) and K(m), i.e., in a single incubation of CHO
      overexpressed cells or rat hepatocytes at 37 degrees C, instead of a parallel
      control evaluation at 4 degrees C.

PMID- 18809733
TI  - Lithium and hematology: established and proposed uses.
AB  - Lithium (as lithium carbonate) is an inexpensive drug, widely used in psychiatry
      for over 50 years in treatment of mood instability (bipolar disorder) and as an
      adjunct to antidepressants. Hematological effects of neutrophilia and increased
      circulating CD34+ cells of marrow origin have long been known. Lithium was at the
      center of hematological investigations in the 1980s, but no definitive use in
      hematology has yet emerged. We review evidence that lithium increases G-CSF and
      augments G-CSF effects. We suggest possible therapeutic uses of lithium in
      neutropenia. In bone marrow transplantation, preharvest lithium-assisted
      hematopoietic stem cell mobilization may be useful as well.

PMID- 18809734
TI  - Regulation of MHC II and CD1 antigen presentation: from ubiquity to security.
AB  - MHC class II and CD1-mediated antigen presentation on various APCs [B cells,
      monocytes, and dendritic cells (DC)] are subject to at least three distinct
      levels of regulation. The first one concerns the expression and structure of the
      antigen-presenting molecules; the second is based on the extracellular
      environment and signals of danger detected. However, a third level of regulation,
      which has been largely overlooked, is determined by lateral associations between
      antigen-presenting molecules and other proteins, their localization in
      specialized microdomains within the plasma membrane, and their trafficking
      pathways. This review focuses on features common to MHC II and CD1 molecules in
      their ability to activate specific T lymphocytes with the objective of addressing
      one basic question: What are the mechanisms regulating antigen presentation by
      MHC II and CD1 molecules within the same cell? Recent studies in immature DC,
      where MHC II and CD1 are coexpressed, suggest that the invariant chain (Ii)
      regulates antigen presentation by either protein. Ii could therefore favor MHC II
      or CD1 antigen presentation and thereby discriminate between antigens.

PMID- 18809735
TI  - Dramatic caspase-dependent apoptosis in antibody-enhanced dengue virus infection
      of human mast cells.
AB  - Severe forms of dengue virus disease, known as dengue hemorrhagic fever and
      dengue shock syndrome, result from an aberrant immune response involving antibody
      dependent enhancement of infection, thrombocytopenia, and a loss of vascular
      integrity, culminating in hemorrhage, shock, and in some cases, death. Several
      studies have indicated that dengue virus infection results in the induction of
      apoptosis of certain cells believed to be contributory players in dengue
      pathogenesis. However, none have specifically examined the role of antibody
      enhancement in the context of induction of apoptosis. Here, we show that antibody
      enhanced dengue virus infection of the FcR-bearing mast cell/basophil KU812 cell
      line results in a massive induction of apoptosis. Confocal microscopy and flow
      cytometry indicate two distinct subpopulations consisting of productively
      infected cells and apoptotic-uninfected bystanders. Apoptosis was found to be
      caspase-dependent, involving global caspase activation and cleavage of poly-ADP
      ribose polymerase (PARP) and D4-guanosine diphosphate dissociation inhibitor (D4
      GDI). Additional FcR-bearing cells, including K562, U937, and human mast cell 1
      (HMC-1), were analyzed for apoptosis induction following infection. Although all
      cells displayed high susceptibility to antibody-enhanced dengue virus infection,
      only cells of a mast cell phenotype (KU812 and HMC-1) were found to undergo
      apoptosis. Dengue-induced apoptosis of KU812 cells was shown to require antibody
      enhanced dengue virus infection by blockade of FcgammaRII. Transfection of KU812
      cells with L-SIGN/DC-SIGNR was able to overcome the requirement for antibody
      enhancement with regard to dengue virus infection and apoptosis.

PMID- 18809736
TI  - Delayed blockade of the kinin B1 receptor reduces renal inflammation and fibrosis
      in obstructive nephropathy.
AB  - Renal fibrosis is the common histological feature of advanced glomerular and
      tubulointerstitial disease leading to end-stage renal disease (ESRD). However,
      specific antifibrotic therapies to slow down the evolution to ESRD are still
      absent. Because persistent inflammation is a key event in the development of
      fibrosis, we hypothesized that the proinflammatory kinin B1 receptor (B1R) could
      be such a new target. Here we show that, in the unilateral ureteral obstruction
      model of renal fibrosis, the B1R is overexpressed and that delayed treatment with
      an orally active nonpeptide B1R antagonist blocks macrophage infiltration,
      leading to a reversal of the level of renal fibrosis. In vivo bone marrow
      transplantation studies as well as in vitro studies on renal cells show that part
      of this antifibrotic mechanism of B1R blockade involves a direct effect on
      resident renal cells by inhibiting chemokine CCL2 and CCL7 expression. These
      findings suggest that blocking the B1R is a promising antifibrotic therapy.

PMID- 18809737
TI  - Differential regulation of bone and body composition in male mice with combined
      inactivation of androgen and estrogen receptor-alpha.
AB  - Osteoporosis and muscle frailty are important health problems in elderly men and
      may be partly related to biological androgen activity. This androgen action can
      be mediated directly through stimulation of the androgen receptor (AR) or
      indirectly through stimulation of estrogen receptor-alpha (ERalpha) following
      aromatization of androgens into estrogens. To assess the differential action of
      AR and ERalpha pathways on bone and body composition, AR-ERalpha double-knockout
      mice were generated and characterized. AR disruption decreased trabecular bone
      mass, whereas ERalpha disruption had no additional effect on the AR-dependent
      trabecular bone loss. In contrast, combined AR and ERalpha inactivation
      additionally reduced cortical bone and muscle mass compared with either AR or
      ERalpha disruption alone. ERalpha inactivation--in the presence or absence of AR-
      increased fat mass. We demonstrate that AR activation is solely responsible for
      the development and maintenance of male trabecular bone mass. Both AR and ERalpha
      activation, however, are needed to optimize the acquisition of cortical bone and
      muscle mass. ERalpha activation alone is sufficient for the regulation of fat
      mass. Our findings clearly define the relative importance of AR and ERalpha
      signaling on trabecular and cortical bone mass as well as body composition in
      male mice.

PMID- 18809738
TI  - Directed induction of anterior and posterior primitive streak by Wnt from
      embryonic stem cells cultured in a chemically defined serum-free medium.
AB  - Formation of the primitive streak (PS) is the initial specification step that
      generates all the mesodermal and endodermal tissue lineages during early
      differentiation. Thus, a therapeutically compatible and efficient method for
      differentiation of the PS is crucial for regenerative medicine. In this study, we
      developed chemically defined serum-free culture conditions for the
      differentiation of embryonic stem (ES) cells into the PS-like cells. Cultures
      supplemented with Wnt showed induction of expression of a PS marker, the
      brachyury gene, followed by induction of the anterior PS markers goosecoid and
      foxa2, a posterior PS marker, evx1, and the endoderm marker sox17. Similar
      differentiation of PS by Wnt was also observed in human ES cells. Moreover, we
      revealed that the activation of the Wnt canonical pathway is essential for PS
      differentiation in mouse ES cells. These results demonstrated that Wnt is an
      essential and sufficient factor for the induction of the PS-like cells in vitro.
      These conditions of induction could constitute the initial step in generating
      therapeutically useful cells of the definitive endoderm lineage, such as
      hepatocytes and pancreatic endocrine cells, under chemically defined conditions.

PMID- 18809740
TI  - Questionable performance of a questionnaire.

PMID- 18809741
TI  - Improving the clarity and transparency of reporting health research: a shared
      obligation and responsibility.

PMID- 18809742
TI  - Is school dental screening a political or a scientific intervention?

PMID- 18809743
TI  - Inorganic chemistry of defensive peroxidases in the human oral cavity.
AB  - The innate host response system is comprised of various mechanisms for
      orchestrating host response to microbial infection of the oral cavity. The
      heterogeneity of the oral cavity and the associated microenvironments that are
      produced give rise to different chemistries that affect the innate defense
      system. One focus of this review is on how these spatial differences influence
      the two major defensive peroxidases of the oral cavity, salivary peroxidase (SPO)
      and myeloperoxidase (MPO). With hydrogen peroxide (H(2)O(2)) as an oxidant, the
      defensive peroxidases use inorganic ions to produce antimicrobials that are
      generally more effective than H(2)O(2) itself. The concentrations of the
      inorganic substrates are different in saliva vs. gingival crevicular fluid (GCF).
      Thus, in the supragingival regime, SPO and MPO work in unison for the exclusive
      production of hypothiocyanite (OSCN(-), a reactive inorganic species), which
      constantly bathes nascent plaques. In contrast, MPO is introduced to the GCF
      during inflammatory response, and in that environment it is capable of producing
      hypochlorite (OCl(-)), a chemically more powerful oxidant that is implicated in
      host tissue damage. A second focus of this review is on inter-person variation
      that may contribute to different peroxidase function. Many of these differences
      are attributed to dietary or smoking practices that alter the concentrations of
      relevant inorganic species in the oral cavity (e.g.: fluoride, F(-); cyanide, CN(
      ); cyanate, OCN(-); thiocyanate, SCN(-); and nitrate, NO(3)(-)). Because of the
      complexity of the host and microflora biology and the associated chemistry, it is
      difficult to establish the significance of the human peroxidase systems during
      the pathogenesis of oral diseases. The problem is particularly complex with
      respect to the gingival sulcus and periodontal pockets (where the very different
      defensive stratagems of GCF and saliva co-mingle). Despite this complexity,
      intriguing in vitro and in vivo studies are reviewed here that reveal the
      interplay between peroxidase function and associated inorganic chemistry.

PMID- 18809745
TI  - Effects of low-energy shock waves on oral bacteria.
AB  - We have recently demonstrated that extracorporeal shock-wave therapy (ESWT) is
      effective in promoting the healing of dermal wounds and in regenerating alveolar
      bone lost through periodontal disease. The objective of the present study was to
      determine any antibacterial effect of ESWT on oral bacteria. Monoculture
      suspensions of 6 bacterial species were treated with 100 to 500 pulses of ESWT at
      energy flux densities (EFD) of 0.12 mJ/mm(2), 0.22 mJ/mm(2), and 0.3 mJ/mm(2).
      Following treatment, aliquots were plated for viability determination and
      compared with untreated controls. ESWT showed a significant microbicidal effect
      for Streptococcus mutans and an unencapsulated strain of Porphyromonas gingivalis
      following as few as 100 pulses at 0.3 mJ/mm(2) (p <or= 0.001). In addition, a
      significant disruption of bacterial aggregates was observed at lower EFDs. No
      significant reduction in viability was observed for all other bacteria at EFDs
      and pulses tested (p > 0.05). These findings suggest that low-energy ESWT may be
      bactericidal for selected oral bacteria.

PMID- 18809746
TI  - P. gingivalis regulates the expression of Cathepsin B and Cystatin C.
AB  - Porphyromonas gingivalis is a major etiological agent of periodontitis that could
      affect the expression of Cathepsins B and C by disrupting the balance between
      these enzymes and their inhibitor, Cystatin C. We tested this hypothesis by
      infecting human oral epithelial cells with P. gingivalis or activating solely by
      its lipopolysaccharide. The mRNA level, the enzymatic activity, and the protein
      expression of Cathepsin B were increased (three-fold) in a dose-dependent manner,
      while those of Cystatin C decreased (five-fold). No changes were observed for
      Cathepsin C. Although activation by lipopolysaccharides led to a delayed
      imbalance (2 days) between Cathepsin B and Cystatin C, this imbalance took place
      very rapidly during the infection (< 6 hrs), indicating that the whole bacterium
      contains components that initiate rapid changes in the transcription rates of
      Cathepsin B and Cystatin C and selectively modify the molecular pathways that
      lead to this imbalance.

PMID- 18809744
TI  - Host defense peptides in the oral cavity and the lung: similarities and
      differences.
AB  - Peptides with broad-spectrum antimicrobial activity are found in the mucosal
      surfaces at many sites in the body, including the airway, the oral cavity, and
      the digestive tract. Based on their in vitro antimicrobial and other
      immunomodulatory activities, these host defense peptides have been proposed to
      play an important role in the innate defense against pathogenic microbial
      colonization. The genes that encode these peptides are up-regulated by pathogens,
      further supporting their role in innate immune defense. However, the differences
      in the local microbial environments between the generally sterile airway and the
      highly colonized oral cavity suggest a more complex role for these peptides in
      innate immunity. For example, beta-defensin genes are induced in the airway by
      all bacteria and Toll-like receptor (TLR) agonists primarily through an NF-kappaB
      mediated pathway. In contrast, the same genes are induced in the gingival
      epithelium by only a subset of bacteria and TLR ligands, via different pathways.
      Furthermore, the environments into which the peptides are secreted--specifically
      saliva, gingival crevicular fluid, and airway surface fluid--differ greatly and
      can effect their respective activities in host defense. In this review, we
      examine the differences and similarities between host defense peptides in the
      oral cavity and the airway, to gain a better understanding of their contributions
      to immunity.

PMID- 18809747
TI  - IL-6 induces osteoblastic differentiation of periodontal ligament cells.
AB  - Interleukin (IL)-6 has been considered as an osteolytic factor involved in
      periodontal disease. However, the function of IL-6 in osteoblastic
      differentiation of periodontal ligament cells is not clear. We examined the
      effects of IL-6 and its soluble receptor (sIL-6R) on osteoblastic differentiation
      of periodontal ligament cells. Osteoblastic differentiation was induced by
      ascorbic acid. Osteoblast markers, including alkaline phosphatase activity and
      Runx2 gene expression, were examined. The mechanism of action of IL-6 on
      osteoblastic differentiation was evaluated by insulin-like growth factor (IGF)-I
      production and specific inhibitors for the IL-6-signaling molecule. IL-6/sIL-6R
      enhanced alkaline phosphatase activity and Runx2. Alkaline phosphatase activity
      was reduced by anti-IGF-I antibody. Mitogen-activated protein kinase and Janus
      protein tyrosine kinase inhibitors diminished alkaline phosphatase induced by IL
      6/sIL-6R. We conclude that IL-6/sIL-6R increases ascorbic-acid-induced alkaline
      phosphatase activity through IGF-I production, implying that IL-6 acts not only
      as an osteolytic factor, but also as a mediator of osteoblastic differentiation
      in periodontal ligament cells.

PMID- 18809748
TI  - Elevated fluoride products enhance remineralization of advanced enamel lesions.
AB  - Caries prevention might benefit from the use of toothpastes containing over 1500
      ppm F. With few clinical studies available, the aim of this pH-cycling study was
      to investigate the dose response between 0 and 5000 ppm F of de- and
      remineralization of advanced (> 150 microm) enamel lesions. Treatments included
      sodium and amine fluoride, and a fluoride-free control. Mineral uptake and loss
      were assessed from solution calcium changes and microradiographs. Treatments with
      5000 ppm F both significantly enhanced remineralization and inhibited
      demineralization when compared with treatments with 1500 ppm F. Slight
      differences in favor of amine fluoride over sodium fluoride were observed. The
      ratio of de- over remineralization rates decreased from 13.8 to 2.1 in the range
      0 to 5000 ppm F. As much as 71 (6)% of the remineralized mineral was calculated
      to be resistant to dissolution during subsequent demineralization periods. With
      5000-ppm-F treatments, more demineralizing episodes per day (10 vs. 2 for
      placebo) would still be repaired by remineralization.

PMID- 18809749
TI  - Neuropeptide Y Y1 receptor effects on pulpal nociceptors.
AB  - Neuropeptide Y (NPY) is an important modulatory neuropeptide that regulates
      several physiological systems, including the activity of sensory neurons. We
      evaluated whether activation of the NPY Y1 receptor could modulate the activity
      of capsaicin-sensitive nociceptors in trigeminal ganglia and dental pulp. We
      tested this hypothesis by measuring capsaicin-stimulated calcitonin gene-related
      peptide release (CGRP) as a measure of nociceptor activity. Capsaicin-evoked CGRP
      release was inhibited by 50% (p < 0.05) in trigeminal ganglia and by 26% (p <
      0.05) in dental pulp when tissues were pre-treated with [Leu(31),Pro(34)]NPY. The
      Y1 receptor was found to co-localize with the capsaicin receptor TRPV1 in
      trigeminal ganglia. These results demonstrate that activation of the Y1 receptor
      results in the inhibition of the activity of capsaicin-sensitive nociceptors in
      the trigeminal ganglia and dental pulp. These findings are relevant to the
      physiological modulation of dental nociceptors by endogenous NPY and demonstrate
      an important novel analgesic target for the treatment of dental pain.

PMID- 18809750
TI  - Effects of ultrasound modes on mandibular osteodistraction.
AB  - Previous studies have shown that therapeutic pulsed ultrasound (pulsed) has
      superior stimulatory effect on bone fracture healing compared with continuous
      ultrasound (continuous). Our predictive hypothesis was that pulsed ultrasound can
      produce better bone formation during mandibular osteodistraction than continuous
      ultrasound. Thirty-six New Zealand rabbits were divided into 3 groups of 12.
      Osteodistraction was performed at 3 mm/day for 5 days. Group 1 received pulsed,
      group 2 received continuous ultrasound, and group 3 was the control group
      (distraction only). Bone formation was assessed by quantitative bone density
      (QBD), mechanical testing, and histological examination. In the first 2 wks post
      distraction, group 2 showed enhanced bone formation more than group 1 (p < 0.05);
      however, in the 3rd and 4th wks, group 1 showed more bone formation than group 2
      (p < 0.05). Earlier stages of bone healing were enhanced more by continuous,
      whereas late stages were enhanced more by pulsed, ultrasound.

PMID- 18809751
TI  - Cathepsin C gene variants in aggressive periodontitis.
AB  - Cathepsin C (CTSC) mutations are known to cause Papillon-Lefevre syndrome. The
      aim of this study was to examine the association of CTSC genotype with
      susceptibility to non-syndromic aggressive periodontitis. The CTSC gene was
      analyzed in 110 persons with generalized aggressive periodontitis in comparison
      with 78 control individuals, after identifying different variants in a cohort of
      100 persons. Five out of 19 discovered variants were included in this association
      study, representing 5 single-nucleotide polymorphism groups in tight linkage
      disequilibrium. The relevance of genotypes on enzyme function was examined. The
      carrier frequency of the missense variant p.I453V was significantly increased in
      persons with disease compared with healthy control individuals (17.3% vs. 6.4%, p
      < 0.05). CTSC activity in leukocytes from individuals harboring this variant was
      significantly reduced (119.8 Delta OD/min*10(5) cells, 95% confidence interval
      17.4-174.9, p = 0.018). No influence of promoter variants was found on mRNA
      expression. The results support the hypothesis that CTSC gene variants contribute
      to increased susceptibility in generalized aggressive periodontitis.

PMID- 18809752
TI  - Protein antigen in serotype k Streptococcus mutans clinical isolates.
AB  - Streptococcus mutans, a major pathogen of dental caries and infective
      endocarditis, is classified into serotypes c, e, f, and k, with serotype k
      strains recently reported to be frequently detected in persons with infective
      endocarditis. Thus, we hypothesized that common properties associated with
      infective endocarditis are present in those strains. Fifty-six oral S. mutans
      strains, including 11 serotype k strains, were analyzed. Western blotting
      analysis revealed expression of the 3 types of glucosyltransferases in all
      strains, while expression of the approximately 190-kDa cell-surface protein (PA)
      was absent in 12 strains, among which the prevalence of serotype k (7/12) was
      significantly high. Furthermore, cellular hydrophobicity and phagocytosis
      susceptibility were lower in the group of serotype k strains. These results
      indicate that the absence of PA expression, low cellular hydrophobicity, and
      phagocytosis susceptibility are common bacterial properties associated with
      serotype k strains, which may be associated with virulence for infective
      endocarditis.

PMID- 18809753
TI  - Affluent neighborhoods reduce excess risk of tooth loss among the poor.
AB  - The effect of neighborhood on health may vary according to the characteristics of
      the residents. We tested the hypothesis that, in affluent neighborhoods, low
      income adults retain more teeth than their income-equivalent peers in poor
      neighborhoods. In 2003, the Adelaide Small Area Dental Study collected
      sociodemographic and tooth retention information from 2860 adults in 60
      neighborhoods. Neighborhood socio-economic position was a census-based composite
      measure. Using multilevel modelling, we fitted a series of two-level random
      intercept variance component models. Findings revealed significant main effects
      for individual and neighborhood predictors and a significant interaction between
      neighborhood disadvantage and low income. In affluent areas, disparities in tooth
      retention were negligible, but in poor neighborhoods, substantial variation in
      tooth retention between individuals was found based on their level of income. Low
      income adults appeared to benefit from living in affluent areas, while wealthier
      adults living in poor neighborhoods did not lose their oral health advantage.

PMID- 18809754
TI  - Limited decalcification/diffusion of self-adhesive cements into dentin.
AB  - Resin cement diffusion into dentin may differ as a function of the pre-treatment
      regimen. Since self-adhesive cements do not require substrate pre-treatment for
      luting, penetration of and interaction with the underlying dentin are questioned.
      We hypothesized that differences in the resin cement diffusion into dentin may
      exist among current commercial adhesive cements. Composite cylinders were luted
      on mid-coronal dentinal surfaces by an etch-and-rinse cement (Calibra), a self
      etching system (Panavia F 2.0), and 4 self-adhesive cements (Multilink Sprint,
      Rely X Unicem, G-Cem, Bis-Cem). Dentin/cement interfacial characteristics were
      analyzed by a staining technique (Masson's trichrome) and by scanning electron
      microscopy. Conventional acid etching resulted in partially infiltrated adhesive
      interfaces differing from those achieved with the application of self-etching
      primer. No hybrid layer and/or resin tag formation was detectable at the
      interfaces bonded with self-adhesive cements. Limited
      decalcification/infiltration was observed for self-adhesive cements into the
      underlying dentin. Self-adhesive cements were not able to demineralize/dissolve
      the smear layer completely.

PMID- 18809755
TI  - Silica nanoparticles to polish tooth surfaces for caries prevention.
AB  - Although silica particles have been used for tooth polishing, polishing with
      nanosized particles has not been reported. Here we hypothesize that such
      polishing may protect tooth surfaces against the damage caused by cariogenic
      bacteria, because the bacteria can be easily removed from such polished surfaces.
      This was tested on human teeth ex vivo. The roughness of the polished surfaces
      was measured with atomic force microscopy (AFM). A considerably lower nanometer
      scale roughness was obtained when silica nanoparticles were used to polish the
      tooth surfaces, as compared with conventional polishing pastes. Bacterial
      attachment to the dental surfaces was studied for Streptococcus mutans, the most
      abundant cariogenic bacteria. We demonstrated that it is easier to remove
      bacteria from areas polished with silica nanoparticles. The results demonstrate
      the advantage of using silica nanoparticles as abrasives for tooth polishing.

PMID- 18809756
TI  - Genetic perturbation of the putative cytoplasmic membrane-proximal salt bridge
      aberrantly activates alpha(4) integrins.
AB  - alpha(4) integrins play a pivotal role in leukocyte migration and tissue-specific
      homing. The ability of integrins to bind ligand is dynamically regulated by
      activation-dependent conformational changes triggered in the cytoplasmic domain.
      An NMR solution structure defined a putative membrane-proximal salt bridge
      between the alpha(IIb)beta(3) integrin cytoplasmic tails, which restrains
      integrins in their low-affinity state. However, the physiological importance of
      this salt bridge in alpha(4) integrin regulation remains to be elucidated. To
      address this question, we disrupted the salt bridge in murine germ line by
      mutating the conserved cytoplasmic arginine R(GFFKR) in alpha(4) integrins. In
      lymphocytes from knock-in mice (alpha(4)-R/A(GFFKR)), alpha(4)beta(1) and
      alpha(4)beta(7) integrins exhibited constitutively up-regulated ligand binding.
      However, transmigration of these cells across VCAM-1 and MAdCAM-1 substrates, or
      across endothelial monolayers, was reduced. Perturbed detachment of the tail
      appeared to cause the reduced cell migration of alpha(4)-R/A(GFFKR) lymphocytes.
      In vivo, alpha(4)-R/A(GFFKR) cells exhibited increased firm adhesion to Peyer
      patch venules but reduced homing to the gut. Our results demonstrate that the
      membrane-proximal salt bridge plays a critical role in supporting proper alpha(4)
      integrin adhesive dynamics. Loss of this interaction destabilizes the nonadhesive
      conformation, and thereby perturbs the properly balanced cycles of adhesion and
      deadhesion required for efficient cell migration.

PMID- 18809757
TI  - Vaccination with autologous tumor-loaded dendritic cells induces clinical and
      immunologic responses in indolent B-cell lymphoma patients with relapsed and
      measurable disease: a pilot study.
AB  - Eighteen relapsed patients with measurable indolent non-Hodgkin lymphoma (NHL)
      were vaccinated with dendritic cells (DCs) loaded with killed autologous tumor
      cells. Six patients had objective clinical responses including 3 continuous
      complete responses (CRs) and 3 partial responses (PRs), with a median follow up
      of 50.5 months. Eight patients had stable disease, whereas 4 had progressive
      disease. Clinical responses were significantly associated with a reduction in
      CD4(+)CD25(+)FOXP3(+) regulatory T cells, an increase in CD3(-)CD56(dim)CD16(+)
      natural killer (NK) cells, and maturation of lymphocytes to the effector memory
      stage in either postvaccination peripheral blood or tumor specimen samples. In
      partial responding patients, vaccination significantly boosted the IFN-gamma
      producing T-cell response to autologous tumor challenge. In one HLA-A*0201(+)
      patient who achieved CR, IL-4 release by circulating T cells in response to tumor
      specific IgH-encoded peptides was also documented. Immunohistochemical analysis
      of tumor biopsies using biotin-conjugated autologous serum samples revealed a
      tumor-restricted humoral response only in the postvaccination serum from
      responding patients. Collectively these results demonstrate that vaccination with
      tumor-loaded DCs may induce both T- and B-cell responses and produces clinical
      benefits in indolent NHL patients with measurable disease. This study is
      registered with the Istituto Superiore di Sanita: http://www.iss.it with protocol
      number 7578-PRE 21-801.

PMID- 18809758
TI  - Down-regulation of hepcidin in porphyria cutanea tarda.
AB  - Hepatic siderosis is common in patients with porphyria cutanea tarda (PCT).
      Mutations in the hereditary hemochromatosis (hh) gene (HFE) explain the siderosis
      in approximately 20% patients, suggesting that the remaining occurrences result
      from additional genetic and environmental factors. Two genes known to modify iron
      loading in hh are hepcidin (HAMP) and hemojuvelin (HJV). To determine if
      mutations in or expression of these genes influenced iron overload in PCT, we
      compared sequences of HAMP and HJV in 96 patients with PCT and 88 HFE C282Y
      homozygotes with marked hepatic iron overload. We also compared hepatic
      expression of these and other iron-related genes in a group of patients with PCT
      and hh. Two intronic polymorphisms in HJV were associated with elevated serum
      ferritin in HFE C282Y homozygotes. No exonic polymorphisms were identified.
      Sequencing of HAMP revealed exonic polymorphisms in 2 patients with PCT:
      heterozygosity for a G-->A transition (G71D substitution) in one and
      heterozygosity for an A-->G transition (K83R substitution) in the other. Hepatic
      HAMP expression in patients with PCT was significantly reduced, regardless of HFE
      genotype, when compared with patients with hh but without PCT with comparable
      iron overload. These data indicate that the hepatic siderosis associated with PCT
      likely results from dysregulated HAMP.

PMID- 18809759
TI  - HapMap scanning of novel human minor histocompatibility antigens.
AB  - Minor histocompatibility antigens (mHags) are molecular targets of allo-immunity
      associated with hematopoietic stem cell transplantation (HSCT) and involved in
      graft-versus-host disease, but they also have beneficial antitumor activity.
      mHags are typically defined by host SNPs that are not shared by the donor and are
      immunologically recognized by cytotoxic T cells isolated from post-HSCT patients.
      However, the number of molecularly identified mHags is still too small to allow
      prospective studies of their clinical importance in transplantation medicine,
      mostly due to the lack of an efficient method for isolation. Here we show that
      when combined with conventional immunologic assays, the large data set from the
      International HapMap Project can be directly used for genetic mapping of novel
      mHags. Based on the immunologically determined mHag status in HapMap panels, a
      target mHag locus can be uniquely mapped through whole genome association
      scanning taking advantage of the unprecedented resolution and power obtained with
      more than 3 000 000 markers. The feasibility of our approach could be supported
      by extensive simulations and further confirmed by actually isolating 2 novel
      mHags as well as 1 previously identified example. The HapMap data set represents
      an invaluable resource for investigating human variation, with obvious
      applications in genetic mapping of clinically relevant human traits.

PMID- 18809760
TI  - Characterization and quantification of clonal heterogeneity among hematopoietic
      stem cells: a model-based approach.
AB  - Hematopoietic stem cells (HSCs) show pronounced heterogeneity in self-renewal and
      differentiation behavior, which is reflected in their repopulation kinetics.
      Here, a single-cell-based mathematical model of HSC organization is used to
      examine the basis of HSC heterogeneity. Our modeling results, which are based on
      the analysis of limiting dilution competitive repopulation experiments in mice,
      demonstrate that small quantitative but clonally fixed differences of cellular
      properties are necessary and sufficient to account for the observed functional
      heterogeneity. The model predicts, and experimental data validate, that
      competitive pressures will amplify small clonal differences into large changes in
      the number of differentiated progeny. We further predict that the repertoire of
      HSC clones will evolve over time. Last, our results suggest that larger
      differences in cellular properties have to be assumed to account for genetically
      determined differences in HSC behavior as observed in different inbred mice
      strains. The model provides comprehensive systemic and quantitative insights into
      the clonal heterogeneity among HSCs with potential applications in predicting the
      behavior of malignant and/or genetically modified cells.

PMID- 18809761
TI  - Homozygous deletion of HFE produces a phenotype similar to the HFE
      p.C282Y/p.C282Y genotype.
AB  - Hemochromatosis is predominantly associated with the HFE p.C282Y homozygous
      genotype, which is carried by approximately 1 person in 200 in Northern European
      populations. However, p.C282Y homozygosity is often characterized by incomplete
      penetrance. Here, we describe the case of a woman who had a major structural
      alteration in the HFE gene. Molecular characterization revealed an Alu-mediated
      recombination leading to the loss of the entire HFE gene sequence. Although
      homozygous for the HFE deleted allele, the woman had a phenotype similar to that
      seen in most women homozygous for the common p.C282Y mutation. Contrasting with
      previously reported results in Hfe knockout and Hfe knockin mice, our report
      gives further evidence that progression of the disease depends on modifying
      factors.

PMID- 18809762
TI  - BCR-ABL fusion transcript types and levels and their interaction with secondary
      genetic changes in determining the phenotype of Philadelphia chromosome-positive
      leukemias.
AB  - It remains unresolved how different BCR-ABL transcripts differentially drive
      lymphoid and myeloid proliferation in Philadelphia chromosome-positive (Ph(+))
      leukemias. We compared BCR-ABL transcript type and level with kinase domain (KD)
      mutation status, genotype, and phenotype in 1855 Ph(+) leukemias. Compared with
      e1a2/p190 BCR-ABL cases, de novo e13-e14a2/p210 Ph(+) lymphoid leukemia more
      frequently showed CML-type background, had higher blast-normalized BCR-ABL
      transcript levels, and more frequent persistent BCR-ABL transcript in the absence
      of detectable lymphoblasts. Secondary lymphoid blast transformation of CML was
      exclusively due to e13/e14a2/p210 BCR-ABL but was associated, at a much higher
      level than p210 myeloid transformation, with acquisition of new KD mutations
      and/or Ph genomic amplification. In contrast, myeloid blast transformation was
      more frequently accompanied by new acquisition of acute myeloid leukemia-type
      chromosomal aberrations, particularly involving the EVI1 and RUNX1 loci.
      Therefore, higher kinase activity by mutation, transcriptional up-regulation or
      gene amplification appears required for lymphoid transformation by p210 BCR-ABL.

PMID- 18809764
TI  - Cancer and thrombosis is a sticky business.

PMID- 18809763
TI  - Shedding some LIGHT on chronic GVHD.

PMID- 18809765
TI  - Killing 2 birds with 1 stone.

PMID- 18809766
TI  - Genetic predisposition for the development of ONJ.

PMID- 18809767
TI  - TAFI: structured for self-destruction.

PMID- 18809769
TI  - Myeloma research goes 3D.

PMID- 18809768
TI  - Polyphosphate: physiologic? Pathologic? Pharmacologic?

PMID- 18809770
TI  - Acute HIV-1 infection: targeting the regulator.

PMID- 18809771
TI  - Expectation for DNA leukemia vaccines.

PMID- 18809772
TI  - Telomerase regulation in HTLV-I infection.

PMID- 18809773
TI  - Mother and child reunion.

PMID- 18809774
TI  - Heparin-induced thrombocytopenia: a historical perspective.

PMID- 18809775
TI  - The hazards of blood transfusion in historical perspective.
AB  - The beginning of the modern era of blood transfusion coincided with World War II
      and the resultant need for massive blood replacement. Soon thereafter, the
      hazards of transfusion, particularly hepatitis and hemolytic transfusion
      reactions, became increasingly evident. The past half century has seen the near
      eradication of transfusion-associated hepatitis as well as the emergence of
      multiple new pathogens, most notably HIV. Specific donor screening assays and
      other interventions have minimized, but not eliminated, infectious disease
      transmission. Other transfusion hazards persist, including human error resulting
      in the inadvertent transfusion of incompatible blood, acute and delayed
      transfusion reactions, transfusion-related acute lung injury (TRALI), transfusion
      associated graft-versus-host disease (TA-GVHD), and transfusion-induced
      immunomodulation. These infectious and noninfectious hazards are reviewed briefly
      in the context of their historical evolution.

PMID- 18809776
TI  - Access for all.

PMID- 18809778
TI  - Dental trauma: part 2. Managing poor prognosis anterior teeth--treatment options
      for the subsequent space in a growing patient.
AB  - Part 1 concentrated on implications of dental trauma especially prior to and
      during orthodontic treatment. This paper examines the literature supporting
      various treatment options for poor prognosis anterior teeth and subsequent space
      generated when these teeth are lost. The role of an interdisciplinary team in
      managing this clinical situation is essential to obtain optimal results and an
      orthodontist is an essential member. Although some treatment options are not
      provided by orthodontists it is important that they have some knowledge of these
      and the latest research that support their use. Other techniques lie very much
      within the orthodontic remit. Treatment options can be split into maintaining the
      failing tooth or extraction and restoration of the edentulous gap. This paper
      reviews various treatment options including periodontal regeneration, surgical
      repositioning and distraction osteogenesis, composite build up to incisal levels
      and decoronation when maintaining a failing tooth. When extraction and
      restoration of edentulous gap is required the following treatment modalities are
      discussed: extraction technique to retain bone quantity, orthodontic space
      closure and opening (site development), autotransplantation, partial denture,
      resin bonded bridge and implants. All these options should be considered and
      available to an interdisciplinary team to ensure optimal care of children with
      anterior teeth of poor prognosis.

PMID- 18809779
TI  - Lowe syndrome: literature review and case report.
AB  - This paper is the first to describe dental findings and orthodontic
      characteristics of a young adult patient with Lowe syndrome. This syndrome is a
      rare genetic disorder inherited by a sex-linked pattern, involving primarily the
      kidneys, eyes and nervous system, which also present oral manifestations. This
      paper also present the results of careful extra and intra-oral evaluations and
      the findings of panoramic and cephalometric radiographs of an 18-year-old male
      with Lowe syndrome.

PMID- 18809780
TI  - The William Houston Medal of the Royal College of Surgeons of Edinburgh 2005.
AB  - This paper describes the orthodontic treatment of two cases that were presented
      by the winner of the William Houston Medal at the Membership in Orthodontics
      examination of the Royal College of Surgeons Edinburgh in 2005. The first case
      presentation is a Class II division 1 malocclusion treated by a combination of
      functional appliance and fixed appliance treatment and the second case
      presentation is a Class III malocclusion treated by a combination of fixed
      appliance treatment and orthognathic surgery.

PMID- 18809781
TI  - Northcroft Memorial Lecture 2007. A century of progress: advances in orthodontics
      since the foundation of the British Society for the Study of Orthodontics.
AB  - The British Orthodontic Society invites outstanding contributors from the field
      of Orthodontics to give the guest lecture in memory of George Northcroft. In 2007
      the guest lecturer was Professor Murray C. Meikle. The article that follows was
      presented as the Northcroft Memorial Lecture 2007 at the British Orthodontic
      Conference, Harrogate, UK, 24th September 2007.

PMID- 18809782
TI  - A comparison of plaster, digital and reconstructed study model accuracy.
AB  - OBJECTIVES: To evaluate the accuracy and reproducibility of a three-dimensional
      (3D) optical laser-scanning device to record the surface detail of plaster study
      models. To determine the accuracy of physical model replicas constructed from the
      3D digital files. DESIGN AND SETTING: A method comparison study using 30 dental
      study models held in the Orthodontic Department, School of Dentistry, Cardiff
      University. MATERIALS AND METHODS: Each model was captured three-dimensionally,
      using a commercially available Minolta VIVID 900 non-contact 3D surface laser
      scanner (Konica Minolta Inc., Tokyo, Japan), a rotary stage and Easy3DScan
      integrating software (TowerGraphics, Lucca, Italy). Linear measurements were
      recorded between landmarks, directly on each of the plaster models and indirectly
      on the 3D digital surface models, on two separate occasions by a single examiner.
      Physical replicas of two digital models were also reconstructed from their
      scanned data files, using a rapid prototyping (RP) manufacturing process, and
      directly evaluated for dimensional accuracy. RESULTS: The mean difference between
      measurements made directly on the plaster models and those made on the 3D digital
      surface models was 0.14 mm, and was not statistically significant (P = 0.237).
      The mean difference between measurements made on both the plaster and virtual
      models and those on the RP models, in the z plane was highly statistically
      significant (P <0.001). CONCLUSIONS: The Minolta VIVID 900 digitizer is a
      reliable device for capturing the surface detail of plaster study models three
      dimensionally in a digital format but physical models of appropriate detail and
      accuracy cannot be reproduced from scanned data using the RP technique described.

PMID- 18809783
TI  - The efficacy of a plasma arc light in orthodontic bonding: a randomized
      controlled clinical trial.
AB  - OBJECTIVE: To evaluate the clinical performance of a plasma arc light (Ortho
      LITE, 3M Unitek, Monrovia, CA, USA) against a conventional tungsten-quartz
      halogen curing light (Visilux 2, 3M Unitek, Monrovia, CA, USA) for direct
      orthodontic bonding. DESIGN: A single centre prospective randomized controlled
      clinical trial. SETTING: The Orthodontic Department at St Luke's Hospital,
      Bradford, UK. SUBJECTS AND METHODS: Forty-three consecutive patients requiring
      fixed appliances from the orthodontic waiting list. A split mouth technique was
      adopted; with quadrants randomly assigned to either the plasma arc light or the
      conventional halogen curing light and bonded directly with APC pre-adjusted
      edgewise brackets (3M Unitek, Monrovia, CA, USA). MAIN OUTCOME MEASURE: Bracket
      failures. SECONDARY OUTCOME MEASURES: Time taken to bond-up the appliances,
      patient sensitivity or discomfort during curing and time to replace failed
      brackets were investigated. RESULTS: No statistically significant difference in
      bracket failure rates over the full course of treatment was found between the
      plasma arc light (6.7%; 95% CI 4.5-10.0) and the halogen curing light (9.5%; 95%
      CI 6.8-13.1). There was no statistically significant difference in bracket
      survival times. The bond-up times were typically reduced by 204 seconds per
      patient with the plasma arc light. There were no differences in patient reported
      sensitivity or discomfort or rebond times. CONCLUSION: The plasma arc light is a
      viable clinical alternative to the conventional halogen curing light with
      benefits for both the clinician and patient due to reduced bonding times.

PMID- 18809784
TI  - Long-term clinical evaluation of bracket failure with a self-etching primer: a
      randomized controlled trial.

PMID- 18809786
TI  - Long-term clinical evaluation of bracket failure with a self-etching primer: a
      randomized controlled trial.

PMID- 18809788
TI  - On treatment blood pressures: which can be trusted, home or clinic?

PMID- 18809789
TI  - Common variation in the WNK1 gene and blood pressure in childhood: the Avon
      Longitudinal Study of Parents and Children.
AB  - WNK1 gene variants have been associated with adult blood pressure. We aimed to
      investigate relationships between WNK1 variants and blood pressure, as well as
      blood pressure change with age, in a longitudinal childhood study. Associations
      between single nucleotide polymorphisms in WNK1 and blood pressure and the rate
      of blood pressure change between 7 and 11 years were examined in the Avon
      Longitudinal Study of Parent and Children Study (n=5326 for systolic blood
      pressure at 11 years). We observed associations (P<0.05) with diastolic blood
      pressure gradient with age for 33 of 82 typed and imputed polymorphisms,
      including polymorphisms in exons 4, 10, and 11 (rs10774466, rs1012729, and
      rs9804992). The minor allele (G) of rs1012729 (frequency: 25.6%) was associated
      with a gender-adjusted change in a diastolic blood pressure gradient of -0.11 mm
      Hg/y (95% CI: -0.20 to -0.03 mm Hg/y; P=0.0054). No associations were shown with
      the systolic blood pressure gradient. At age 11 years, 30 polymorphisms showed
      association (P<0.05) with systolic blood pressure, including variants in exons 4
      and 10 (rs10774466 and rs1012729). Only 3 polymorphisms were associated with
      diastolic blood pressure at 11 years. In exploration of polymorphism-dietary
      cation interactions on systolic blood pressure at 11 years, 59 reached
      significance (P<0.05; 12.3 expected by chance), mostly (n=33) related to dietary
      calcium. The findings show that common intronic and exonic WNK1 variants are
      associated with diastolic blood pressure gradient from 7 to 11 years and with
      systolic blood pressure at 11 years. Our study suggests that previously reported
      effects of WNK1 variants on blood pressure are mediated via effects on the
      gradient of blood pressure change with age.

PMID- 18809790
TI  - Angiotensin-converting enzyme 2: cardioprotective player in the renin-angiotensin
      system?

PMID- 18809791
TI  - Changes in home versus clinic blood pressure with antihypertensive treatments: a
      meta-analysis.
AB  - Home blood pressure (HBP) monitoring is recommended for assessing the effects of
      antihypertensive treatment, but it is not clear how the treatment-induced changes
      in HBP compare with the changes in clinic blood pressure (CBP). We searched
      PubMed using the terms "home or self-measured blood pressure," and selected
      articles in which the changes in CBP and HBP (using the upper arm oscillometric
      method) induced by antihypertensive drugs were presented. We performed a
      systematic review of 30 articles published before March 2008 that included a
      total of 6794 subjects. As there was significant heterogeneity in most of the
      outcomes, a random effects model was used for the meta-analyses. The mean changes
      (+/-SE) in CBP and HBP (systolic/diastolic) were -15.2+/-0.03/-10.3+/-0.03 mm Hg
      and -12.2+/-0.04/-8.0+/-0.04 mm Hg respectively, although there were wide
      varieties of differences in the reduction between HBP and CBP. The reductions in
      CBP were correlated with those of HBP (systolic BP; r=0.66, B=0.48, diastolic BP;
      r=0.71, B=0.52, P<0.001). In 7 studies that also included 24-hour BP monitoring,
      the reduction of HBP was greater than that of 24-hour BP in systolic (HBP; 
      12.6+/-0.06 mm Hg, 24-hour BP; -11.9+/-0.04 mm Hg, P<0.001). In 5 studies that
      included daytime and nighttime systolic BP separately, HBP decreased 15% more
      than daytime ambulatory BP and 30% more than nighttime ambulatory BP. In
      conclusion, HBP falls approximately 20% less than CBP with antihypertensive
      treatments. Daytime systolic BP falls 15% less and nighttime systolic BP falls
      30% less than home systolic BP.

PMID- 18809792
TI  - Transgenic angiotensin-converting enzyme 2 overexpression in vessels of SHRSP
      rats reduces blood pressure and improves endothelial function.
AB  - Rat models of hypertension, eg, spontaneously hypertensive stroke-prone rats
      (SHRSP), display reduced angiotensin-converting enzyme 2 (ACE2) mRNA and protein
      expression compared with control animals. The aim of this study was to
      investigate the role of ACE2 in the pathogenesis of hypertension in these models.
      Therefore, we generated transgenic rats on a SHRSP genetic background expressing
      the human ACE2 in vascular smooth muscle cells by the use of the SM22 promoter,
      called SHRSP-ACE2. In these transgenic rats vascular smooth muscle expression of
      human ACE2 was confirmed by RNase protection, real-time RT-PCR, and ACE2 activity
      assays. Transgene expression leads to significantly increased circulating levels
      of angiotensin-(1-7), a prominent product of ACE2. Mean arterial blood pressure
      was reduced in SHRSP-ACE2 compared to SHRSP rats, and the vasoconstrictive
      response to intraarterial administration of angiotensin II was attenuated. The
      latter effect was abolished by previous administration of an ACE2 inhibitor. To
      evaluate the endothelial function in vivo, endothelium-dependent and endothelium
      independent agents such as acetylcholine and sodium nitroprusside, respectively,
      were applied to the descending thoracic aorta and blood pressure was monitored.
      Endothelial function turned out to be significantly improved in SHRSP-ACE2 rats
      compared to SHRSP. These data demonstrate that vascular ACE2 overexpression in
      SHRSP reduces hypertension probably by locally degrading angiotensin II and
      improving endothelial function. Thus, activation of the ACE2/angiotensin-(1-7)
      axis may be a novel therapeutic strategy in hypertension.

PMID- 18809793
TI  - Mechanosensitive N-methyl-D-aspartate receptors contribute to sensory activation
      in the rat renal pelvis.
AB  - The N-methyl-D-aspartate (NMDA) subtype of the ionotropic glutamate receptor is
      found in the periphery. The present study tested whether NMDA receptors (NMDARs)
      are present in the ends of afferent renal nerves in the renal pelvis, an area
      concerned mainly with transmitting sensation and the to reflex regulation of body
      fluid. The main NMDAR subunit, NMDAzeta1, was found to be more abundant in the
      renal pelvis than the renal cortex and medulla, and was mainly colocalized with
      the pan-neuronal marker PGP9.5 or the sensory nerve marker, the neurokinin-1
      receptor. However, NMDAzeta1 mRNA was undetectable, suggesting that it might be
      synthesized outside the renal pelvis. Intrarenal arterial administration of the
      specific ion channel blocker (+)-MK-801, but not the inactive enantiomer (-)-MK
      801, decreased urine output and sodium excretion. High doses of (+)-MK-801 also
      caused regional vasoconstriction in the renal cortex, as determined by laser
      Doppler flowmetry. Intrapelvic administration of the NMDAR ligand D-serine caused
      a dose-dependent increase in substance P (SP) release and afferent renal nerve
      activity, but had no effect on arterial pressure. The D-serine-induced sensory
      activation and SP release were abrogated by (+)-MK-801, the SP receptor blocker L
      703,606, or dorsal rhizotomy. Increasing intrapelvic pressure resulted in an
      increase in afferent renal nerve activity and a diuretic/natriuretic response.
      Interestingly, these effects were attenuated by prior administration of (+)-MK
      801. These results indicate that NMDAR-positive sensory nerves are present in the
      renal pelvis and contribute to the renorenal reflex control of body fluid.

PMID- 18809794
TI  - Functional impairment of von Willebrand factor in hypertrophic cardiomyopathy:
      relation to rest and exercise obstruction.
AB  - BACKGROUND: Hypertrophic obstructive cardiomyopathy submits blood to conditions
      of high shear stress. High shear stress impairs von Willebrand factor (VWF) and
      promotes abnormal bleeding in aortic stenosis. We sought to evaluate VWF
      impairment and its relationships to baseline or exercise obstruction in
      hypertrophic cardiomyopathy (HCM). METHODS AND RESULTS: Outflow obstruction was
      evaluated by rest and exercise echocardiography in 62 patients with HCM (age 44+/
      16 years, 40 males). HCM was considered obstructive in 28 patients with rest or
      exercise peak gradient >or=30 mm Hg. Blood was sampled to assess VWF. History of
      bleeding was recorded. Baseline median (25th to 75th percentile) peak gradient
      was 11 (5-62) mm Hg. Shear-induced platelet adhesion was impaired in patients
      with obstructive HCM. The ratio of VWF-collagen-binding activity to antigen and
      the percentage of high-molecular-weight multimers of VWF were lower in patients
      with obstructive HCM than in those with nonobstructive HCM (0.49 [0.43 to 0.59]
      versus 0.82 [0.73 to 1.03] and 5.0% [3.9% to 7.2%] versus 11.7% [10.8% to 12.5%],
      respectively; both P<0.0001). Platelet adhesion time, VWF-collagen-binding
      activity-to-antigen ratio, and the percentage of high-molecular-weight multimers
      correlated closely and independently with peak gradient (r=0.81, r=-0.68, and r=
      0.89, respectively; all P<0.0001). According to receiver operating characteristic
      curves, a peak gradient threshold of 15 mm Hg at rest and 35 mm Hg during
      exercise was sufficient to impair VWF. Conversely, VWF function tended to improve
      with a decrease in peak gradient. Obstructive HCM patients had a trend toward
      abnormal spontaneous bleeding. CONCLUSIONS: In obstructive HCM, VWF impairment is
      frequent and is closely and independently related to the magnitude of outflow
      obstruction. A resting peak gradient of 15 mm Hg is sufficient to impair VWF. VWF
      abnormalities might favor abnormal bleeding in this setting.

PMID- 18809795
TI  - Passive smoking and risk of peripheral arterial disease and ischemic stroke in
      Chinese women who never smoked.
AB  - BACKGROUND: The association between secondhand smoke (SHS) and risk of peripheral
      arterial disease (PAD) and stroke remains uncertain. METHODS AND RESULTS: We
      examined the relationship between SHS and cardiovascular diseases, particularly
      PAD and stroke, in Chinese women who never smoked from a population-based cross
      sectional study in Beijing, China. SHS exposure was defined as exposure to
      another person's tobacco smoke at home or in the workplace. Cardiovascular
      disease events included coronary heart disease, stroke, and PAD. PAD was defined
      by signs of intermittent claudication as measured by the World Health
      Organization Rose questionnaire and an ankle-brachial index of <0.90. Among 1209
      women who never smoked, 39.5% were exposed to SHS at home or in workplaces. Those
      individuals who were exposed to SHS had a significantly higher risk of coronary
      heart disease (adjusted odds ratio [OR], 1.69; 95% CI, 1.31 to 2.18) and ischemic
      stroke (OR, 1.56; 95% CI, 1.03 to 2.35) than those never exposed to SHS after
      adjustment for 13 potential risk factors. The adjusted ORs of PAD defined by
      intermittent claudication, by ankle-brachial index <0.90, and by either
      intermittent claudication or ankle-brachial index <0.90 were 1.87 (95% CI, 1.30
      to 2.68), 1.47 (95% CI, 1.07 to 2.03), and 1.67 (95% CI, 1.23 to 2.16),
      respectively. Dose-response relationships were found between SHS exposure amount
      (cigarettes per day) and duration (minutes per day) and increasing prevalence of
      coronary heart disease, ischemic stroke, and PAD. CONCLUSIONS: In China, SHS
      exposure in women is highly prevalent. In addition to being a risk factor for
      coronary heart disease, SHS should be considered an important risk factor for
      ischemic stroke and PAD in nonsmoking women.

PMID- 18809796
TI  - Prevalence, clinical significance, and natural history of left ventricular apical
      aneurysms in hypertrophic cardiomyopathy.
AB  - BACKGROUND: Hypertrophic cardiomyopathy (HCM) is the most common genetic heart
      disease characterized by a diverse clinical and phenotypic spectrum. This study
      reports the prevalence, morphology, clinical course, and management of an
      underrecognized subgroup of HCM patients with left ventricular apical aneurysms.
      METHODS AND RESULTS: Of 1299 HCM patients, 28 (2%) were identified with left
      ventricular apical aneurysms, including a pair of identical twins. Aneurysms were
      recognized at a wide age range (26 to 83 years), including 12 patients (43%) who
      were <or=50 years of age. Apical aneurysms varied considerably in size (maximum
      dimension, 10 to 66 mm), were dyskinetic/akinetic with thin rims, and were
      associated with transmural (and often more extensive) myocardial scarring
      identified by late gadolinium enhancement cardiovascular magnetic resonance.
      Apical aneurysms were recognized by echocardiography in only 16 of 28 patients
      (57%) but by cardiovascular magnetic resonance in the 12 patients undetected by
      echocardiography. Left ventricular chamber morphology varied; however, 19
      patients (68%) showed an "hourglass" contour, with midventricular hypertrophy
      producing muscular narrowing and intracavitary gradients in 9 patients (74+/-42
      mm Hg). Sarcomeric protein missense mutations known to cause other phenotypic
      expressions of HCM were present in 3 patients. Over 4.1+/-3.7 years of follow-up,
      12 patients (43%) with left ventricular apical aneurysms experienced adverse
      disease complications (event rate, 10.5%/y), including sudden death, appropriate
      implantable cardioverter-defibrillator discharges, nonfatal thromboembolic
      stroke, and progressive heart failure and death. CONCLUSIONS: Patients with left
      ventricular apical aneurysms represent an underappreciated subset in the
      heterogeneous HCM disease spectrum with important clinical implications, often
      requiring a high index of suspicion and cardiovascular magnetic resonance for
      identification. Apical aneurysms in HCM are associated with substantial
      cardiovascular morbidity and mortality and raise novel treatment considerations.

PMID- 18809797
TI  - Incidence and risk factors for stroke in American Indians: the Strong Heart
      Study.
AB  - BACKGROUND: There are few published data on the incidence of fatal and nonfatal
      stroke in American Indians. The aims of this observational study were to
      determine the incidence of stroke and to elucidate stroke risk factors among
      American Indians. METHODS AND RESULTS: This report is based on 4549 participants
      aged 45 to 74 years at enrollment in the Strong Heart Study, the largest
      longitudinal, population-based study of cardiovascular disease and its risk
      factors in a diverse group of American Indians. At baseline examination in 1989
      to 1992, 42 participants (age- and sex-adjusted prevalence proportion 1132/100
      000, adjusted to the age and sex distribution of the US adult population in 1990)
      had prevalent stroke. Through December 2004, 306 (6.8%) of 4507 participants
      without prior stroke suffered a first stroke at a mean age of 66.5 years. The age
      and sex-adjusted incidence was 679/100 000 person-years. Nonhemorrhagic cerebral
      infarction occurred in 86% of participants with incident strokes; 14% had
      hemorrhagic stroke. The overall age-adjusted 30-day case-fatality rate from first
      stroke was 18%, with a 1-year case-fatality rate of 32%. Age, diastolic blood
      pressure, fasting glucose, hemoglobin A(1c,) smoking, albuminuria, hypertension,
      prehypertension, and diabetes mellitus were risk factors for incident stroke.
      CONCLUSIONS: Compared with US white and black populations, American Indians have
      a higher incidence of stroke. The case-fatality rate for first stroke is also
      higher in American Indians than in the US white or black population in the same
      age range. Our findings suggest that blood pressure and glucose control and
      smoking avoidance may be important avenues for stroke prevention in this
      population.

PMID- 18809798
TI  - Conditional dicer gene deletion in the postnatal myocardium provokes spontaneous
      cardiac remodeling.
AB  - BACKGROUND: Dicer, an RNAse III endonuclease critical for processing of pre
      microRNAs (miRNAs) into mature 22-nucleotide miRNAs, has proven a useful target
      to dissect the significance of miRNAs biogenesis in mammalian biology. METHODS
      AND RESULTS: To circumvent the embryonic lethality associated with germline null
      mutations for Dicer, we triggered conditional Dicer loss through the use of a
      tamoxifen-inducible Cre recombinase in the postnatal murine myocardium. Targeted
      Dicer deletion in 3-week-old mice provoked premature death within 1 week
      accompanied by mild ventricular remodeling and dramatic atrial enlargement. In
      the adult myocardium, loss of Dicer induced rapid and dramatic biventricular
      enlargement, accompanied by myocyte hypertrophy, myofiber disarray, ventricular
      fibrosis, and strong induction of fetal gene transcripts. Comparative miRNA
      profiling revealed a set of miRNAs that imply causality between miRNA depletion
      and spontaneous cardiac remodeling. CONCLUSIONS: Overall, these results indicate
      that modifications in miRNA biogenesis affect both juvenile and adult myocardial
      morphology and function.

PMID- 18809799
TI  - Clinical outcome after surgical correction of mitral regurgitation due to
      papillary muscle rupture.
AB  - BACKGROUND: Papillary muscle rupture (PMR) is an infrequent but catastrophic
      complication of acute myocardial infarction (MI). Although always considered,
      surgical treatment is often denied because of high operative mortality. Moreover,
      the effects of surgery for PMR on long-term outcome, particularly compared with
      expected outcome after MI, are undefined. METHODS AND RESULTS: Fifty-four
      consecutive patients (age, 70+/-8 years; 74% male) underwent mitral surgery for
      post-MI PMR from January 1980 through December 2000. Severe presentation
      (cardiogenic shock, pulmonary edema, or cardiac arrest) was noted in 91%
      preoperatively. Performance of coronary artery bypass graft was associated with
      lower operative mortality (odds ratio, 0.18; 95% CI, 0.04 to 0.83; P=0.011),
      whereas there was a trend for lower mortality after surgery after 1990 (odds
      ratio, 0.28; 95% CI, 0.06 to 1.3). Thus, operative mortality (overall, 18.5%)
      decreased from 67% up to 1990 without coronary artery bypass graft to 8.7% after
      1990 with coronary artery bypass graft. Overall 5-year survival was 65+/-7%, and
      survival free of congestive heart failure was 52+/-7%. Five-year survival of 30
      day operative survivors was 79+/-4%, identical (P=0.24) to that of matched
      controls with MI (similar age, sex, ejection fraction, MI location, and MI year).
      Survival free of congestive heart failure was similar in PMR cases and MI
      controls (10-year survival, 28+/-8% versus 36+/-6%; P=0.46). CONCLUSIONS: Surgery
      for post-MI PMR involves a notable operative mortality, but there are recent
      trends for lower operative risk, particularly with associated coronary artery
      bypass graft. Long term after surgery, outcome is restored to that of similar MI
      without PMR. These encouraging observations emphasize the importance of prompt
      diagnosis and aggressive therapeutic approach for patients incurring PMR after
      MI.

PMID- 18809800
TI  - Hypertension subtype and risk of cardiovascular disease in Chinese adults.
AB  - BACKGROUND: We examined the relationship between hypertension subtype and
      cardiovascular disease incidence and mortality in Chinese adults. METHODS AND
      RESULTS: We conducted a prospective cohort study in a nationally representative
      sample of 169 871 Chinese men and women aged >or=40 years. Data on systolic (SBP)
      and diastolic blood pressure (DBP) and other variables were obtained at a
      baseline examination in 1991 with the use of standard protocols. Follow-up
      evaluation was conducted in 1999-2000, with a response rate of 93.4%.
      Hypertension subtypes were defined as combined systolic and diastolic
      hypertension (SBP >or=140 and DBP >or=90 mm Hg), isolated systolic hypertension
      (SBP >or=140 and DBP <90 mm Hg), isolated diastolic hypertension (SBP <140 and
      DBP >or=90 mm Hg), and 2 categories of treated hypertension (SBP <140 and DBP <90
      mm Hg or SBP >or=140 and/or DBP >or=90 mm Hg). After participants with missing BP
      values were excluded, 169 577 adults were included in the analyses. Compared with
      normotensives, relative risks (95% CIs) of cardiovascular disease incidence and
      mortality were 2.73 (2.60 to 2.86) and 2.53 (2.39 to 2.68) for combined systolic
      and diastolic hypertension, 1.78 (1.69 to 1.87) and 1.68 (1.58 to 1.78) for
      isolated systolic hypertension, 1.59 (1.43 to 1.76) and 1.45 (1.27 to 1.65) for
      isolated diastolic hypertension, 2.01 (1.64 to 2.48) and 1.61 (1.28 to 2.03) for
      treated hypertension with SBP <140 and DBP <90 mm Hg, and 3.37 (3.07 to 3.69) and
      2.88 (2.60 to 3.19) for treated hypertension with SBP >or=140 and/or DBP >or=90
      mm Hg, respectively, after adjustment for important covariables. CONCLUSIONS: Our
      results indicate that all hypertension subtypes are associated with significantly
      increased risk of cardiovascular disease in Chinese adults. Primary prevention of
      hypertension should be a public health priority in the Chinese population.

PMID- 18809801
TI  - Images in cardiovascular medicine. Mycotic left ventricular false aneurysm at the
      site of an apical vent presenting 24 years after aortic valve surgery.

PMID- 18809802
TI  - Images in cardiovascular medicine. Eustachian valve thrombosis.

PMID- 18809803
TI  - Letter by Razzolini and Tarantini regarding article, "Restrictive left
      ventricular filling pattern does not result from increased left atrial pressure
      alone".

PMID- 18809805
TI  - "POBA Plus": will the balloon regain its luster?

PMID- 18809806
TI  - A plethora of prognostic pearls.

PMID- 18809807
TI  - Suppression of the JNK pathway by induction of a metabolic stress response
      prevents vascular injury and dysfunction.
AB  - BACKGROUND: Oxidative injury and dysfunction of the vascular endothelium are
      early and causal features of many vascular diseases. Single antioxidant
      strategies to prevent vascular injury have met with mixed results. METHODS AND
      RESULTS: Here, we report that induction of a metabolic stress response with
      adenosine monophosphate kinase (AMPK) prevents oxidative endothelial cell injury.
      This response is characterized by stabilization of the mitochondrion and
      increased mitochondrial biogenesis, resulting in attenuation of oxidative c-Jun N
      terminal kinase (JNK) activation. We report that peroxisome proliferator
      coactivator 1alpha is a key downstream target of AMPK that is both necessary and
      sufficient for the metabolic stress response and JNK attenuation. Moreover,
      induction of the metabolic stress response in vivo attenuates reactive oxygen
      species-mediated JNK activation and endothelial dysfunction in response to
      angiotensin II in wild-type mice but not in animals lacking either the
      endothelial isoform of AMPK or peroxisome proliferator coactivator 1alpha.
      CONCLUSIONS: These data highlight AMPK and peroxisome proliferator coactivator
      1alpha as potential therapeutic targets for the amelioration of endothelial
      dysfunction and, as a consequence, vascular disease.

PMID- 18809808
TI  - Ethnic differences in cardiovascular drug response: potential contribution of
      pharmacogenetics.

PMID- 18809809
TI  - Images in cardiovascular medicine. Central sleep apnea induces ventricular
      bigeminus: conclusions from a single polygraphy.

PMID- 18809811
TI  - Missed opportunities for interval empathy in lung cancer communication.
AB  - BACKGROUND: Empathy is important in patient-physician communication and is
      associated with improved patient satisfaction and adherence to physicians'
      recommendations. METHODS: To evaluate empathic opportunities and physician
      responses, we conducted a qualitative thematic analysis of 20 audiorecorded,
      transcribed consultations between patients with lung cancer and their thoracic
      surgeons or oncologists, from a larger observational study of 137 patients in a
      Veterans Affairs hospital in the southern United States. Using qualitative
      analysis, we collaboratively developed themes and subthemes until saturation.
      Then, each transcript was coded, using grounded theory methods, until consensus
      was achieved, counting and sequentially analyzing patient empathic opportunities
      and physician responses. RESULTS: Subthemes regarding patients' statements about
      lung cancer included (1) morbidity or mortality concerns, (2) cancer-related
      symptoms, (3) relationship to smoking, (4) decisions about treatment, (5) beliefs
      about or mistrust of medical care, (6) factors limiting ability to treat cancer,
      and (7) confusion regarding cancer status and treatment. We identified 384
      empathic opportunities and found that physicians had responded empathically to 39
      (10%) of them. Otherwise, physicians provided little emotional support, often
      shifting to biomedical questions and statements. We defined this phenomenon as
      missed opportunities for "interval empathy." When empathy was provided, 50% of
      these statements occurred in the last one-third of the encounter, whereas
      patients' concerns were evenly raised throughout the encounter. CONCLUSIONS:
      Physicians rarely responded empathically to the concerns raised by patients with
      lung cancer, and empathic responses that did occur were more frequently in the
      last third of the encounter. Our results may provide a typologic approach to help
      physicians recognize empathic opportunities and with further development may aid
      in improving physicians' communication skills.

PMID- 18809810
TI  - So much to do, so little time: care for the socially disadvantaged and the 15
      minute visit.
AB  - There is so much to do in primary care, and so little time to do it. During 15
      minute visits, physicians are expected to form partnerships with patients and
      their families, address complex acute and chronic biomedical and psychosocial
      problems, provide preventive care, coordinate care with specialists, and ensure
      informed decision making that respects patients' needs and preferences. This is a
      challenging task during straightforward visits, and it is nearly impossible when
      caring for socially disadvantaged patients with complex biomedical and
      psychosocial problems and multiple barriers to care. Consider the following
      scenario.

PMID- 18809812
TI  - Calorie restriction and bone health in young, overweight individuals.
AB  - BACKGROUND: Calorie restriction (CR) is promoted to increase longevity, yet this
      regimen could lead to bone loss and fracture and therefore affect quality of
      life. METHODS: Forty-six individuals were randomized to 4 groups for 6 months:
      (1) healthy diet (control group); (2) 25% CR from baseline energy requirements
      (CR group); (3) 25% energy deficit by a combination of CR and increased aerobic
      exercise (CR + EX group); and (4) low-calorie diet (890 kcal/d; goal, 15% weight
      loss) followed by weight maintenance (LCD group). Bone mineral density (total
      body and hip by dual-energy x-ray absorptiometry) and serum bone markers (bone
      specific alkaline phosphatase, osteocalcin, cross-linked C-telopeptide of type I
      collagen, and cross-linked N-telopeptide of type I collagen) were measured at
      baseline and after 6 months. RESULTS: Mean +/- SE body weight was reduced by 
      1.0% +/- 1.1% (control), -10.4% +/- 0.9% (CR), -10.0% +/- 0.8% (CR + EX), and 
      13.9% +/- 0.7% (LCD). Compared with the control group, none of the groups showed
      any change in bone mineral density for total body or hip. Bone resorption by
      serum cross-linked C-telopeptide of type I collagen was increased in all 3
      intervention groups, with the largest change observed in the LCD group (CR, 23%
      +/- 10%; CR + EX, 22% +/- 9%; and LCD, 74% +/- 16% vs control, 4% +/- 10%). Serum
      levels of cross-linked N-telopeptide of type I collagen were also increased in
      the LCD group. With regard to bone formation, bone alkaline phosphatase levels
      were decreased in the CR group (-23% +/- 10%) but were unchanged in the CR + EX,
      LCD, and control groups. CONCLUSIONS: Moderate CR, with or without exercise, that
      preserves calcium intake for 6 months leads to large changes in body composition
      without significant bone loss in young adults. Longer studies with assessments of
      bone architecture are needed to confirm that CR nutrient-dense diets have no
      deleterious effect on bone health. TRIAL REGISTRATION: clinicaltrials.gov
      Identifier: NCT00099151.

PMID- 18809813
TI  - Insulin therapy, hyperglycemia, and hypertension in type 1 diabetes mellitus.
AB  - BACKGROUND: Diabetes mellitus and hypertension are closely linked, but the long
      term blood pressure effects of glucose-lowering therapy and hyperglycemia are not
      clear. METHODS: We examined the effects of intensive insulin therapy and
      hyperglycemia on the development of hypertension in the Diabetes Control and
      Complications Trial (DCCT) and its observational follow-up, the Epidemiology of
      Diabetes Intervention and Complications (EDIC) study. Incident hypertension was
      defined as 2 consecutive study visits with a systolic blood pressure of 140 mm Hg
      or higher, a diastolic blood pressure of 90 mm Hg or higher, or use of
      antihypertensive medications to treat high blood pressure. RESULTS: Participants
      were enrolled from August 23, 1983, through June 30, 1989. During a 15.8-year
      median follow-up, 630 of 1441 participants developed hypertension. During the
      DCCT, the incidence of hypertension was similar comparing participants assigned
      to intensive vs conventional therapy. However, intensive therapy during the DCCT
      reduced the risk of incident hypertension by 24% during EDIC study follow-up
      (hazard ratio, 0.76; 95% confidence interval [CI], 0.64-0.92). A higher
      hemoglobin A(1c) level, measured at baseline or throughout follow-up, was
      associated with increased risk for incident hypertension (adjusted hazard ratios,
      1.11 [95% CI, 1.06-1.17] and 1.25 [95% CI, 1.14-1.37], respectively, for each 1%
      higher hemoglobin A(1c) level), and glycemic control appeared to mediate the
      antihypertensive benefit of intensive therapy. Older age, male sex, family
      history of hypertension, greater baseline body mass index, weight gain, and
      greater albumin excretion rate were independently associated with increased risk
      of hypertension. CONCLUSIONS: Hyperglycemia is a risk factor for incident
      hypertension in type 1 diabetes, and intensive insulin therapy reduces the long
      term risk of developing hypertension.

PMID- 18809814
TI  - Neighborhood income, health insurance, and prehospital delay for myocardial
      infarction: the atherosclerosis risk in communities study.
AB  - BACKGROUND: Outcomes following an acute myocardial infarction (AMI) are generally
      more favorable if prehospital delay time is minimized. METHODS: We examined the
      association of neighborhood household income (nINC) and health insurance status
      with prehospital delay among a weighted sample of 9700 men and women with a
      validated, definite, or probable AMI in the Atherosclerosis Risk in Communities
      (ARIC) community surveillance study (1993-2002). Weighted multinomial regression
      with generalized estimation equations was used to estimate odds ratios (ORs) and
      95% confidence intervals (CIs) and to account for the clustering of patients
      within census tracts. RESULTS: Low nINC was associated with a higher odds of long
      vs short delay (OR, 1.46; 95% CI, 1.09-1.96) and medium vs short delay (OR, 1.43;
      95% CI, 1.12-1.81) compared with high nINC in a model including age, sex, race,
      diabetes, hypertension, presence of chest pain, arrival at the hospital via
      emergency medical service, distance from residence to hospital, study community,
      and year of AMI event. Meanwhile, compared with patients with prepaid insurance
      or prepaid plus Medicare, patients with Medicaid were more likely to have a long
      vs short delay (OR, 1.87; 95% CI, 1.10-3.19) and a medium vs short delay (OR,
      1.76; 95% CI, 1.13-2.74). CONCLUSIONS: Both low nINC and being a Medicaid
      recipient are associated with longer prehospital delay. Reducing socioeconomic
      and insurance disparities in prehospital delay is critical because excess delay
      time may hinder effective care for AMI.

PMID- 18809815
TI  - Trade-offs in cervical cancer prevention: balancing benefits and risks.
AB  - BACKGROUND: New screening and vaccination technologies will provide women with
      more options for cervical cancer prevention. Because the risk of cervical cancer
      diminishes with effective routine screening, women may wish to consider
      additional attributes, such as the likelihood of false-positive results and
      diagnostic procedures for mild abnormalities likely to resolve without
      intervention in their screening choices. METHODS: We used an empirically
      calibrated simulation model of cervical cancer in the United States to assess the
      benefits and potential risks associated with prevention strategies differing by
      primary screening test, triage test for abnormal results (cytologic testing,
      human papillomavirus [HPV] DNA test), and screening frequency. Outcomes included
      colposcopy referrals, cervical intraepithelial neoplasia (CIN) types 1 and 2 or
      3, lifetime cancer risk, and quality-adjusted life expectancy. RESULTS: Across
      strategies, colposcopy referrals and diagnostic workups varied 3-fold, although
      diagnostic rates of CIN 2 or 3 were similar and 95% of positive screening test
      results were for mild abnormalities likely to resolve on their own. For a
      representative group of a thousand 20-year-old women undergoing triennial
      screening for 10 years, we expect 1038 colposcopy referrals (7 CIN 2 or 3
      diagnoses) from combined cytologic and HPV DNA testing and fewer than 200
      referrals (6-7 CIN 2 or 3 diagnoses) for strategies that use triage testing.
      Similarly, for a thousand 40-year-old women, combined cytologic and HPV DNA
      testing led to 489 referrals (9 CIN 2 or 3), whereas alternative strategies
      resulted in fewer than 150 referrals (7-8 CIN 2 or 3). Using cytologic testing
      followed by triage testing in younger women minimizes both diagnostic workups and
      positive HPV test results, whereas in older women diagnostic workups are
      minimized with HPV DNA testing followed by cytologic triage testing. CONCLUSIONS:
      Clinically relevant information highlighting trade-offs among cervical cancer
      prevention strategies allows for inclusion of personal preferences into women's
      decision making about screening and provides additional dimensions to the
      construction of clinical guidelines.

PMID- 18809816
TI  - Frequency of and risk factors for preventable medication-related hospital
      admissions in the Netherlands.
AB  - BACKGROUND: Medication-related problems that lead to hospitalization have been
      the subject of many studies, many of which were limited to 1 hospital or lacked
      patient follow-up. Furthermore, little information exists on potential risk
      factors associated with preventable medication-related hospitalizations. METHODS:
      A prospective multicenter study was conducted to determine the frequency and
      patient outcomes of medication-related hospital admissions. A case-control design
      was used to determine risk factors for potentially preventable admissions. All
      unplanned admissions in 21 hospitals were assessed during 40 days. Controls were
      patients admitted for elective surgery. Cases and controls were followed up until
      hospital discharge. The frequency of medication-related hospital admissions,
      potential preventability, and outcomes were assessed. For potentially preventable
      medication-related admissions, risk factors were identified in the case-control
      study. RESULTS: Almost 13,000 unplanned admissions were screened, of which 714
      (5.6%) were medication related. Almost half (46.5%) of these admissions were
      potentially preventable, resulting in 332 case patients matched with 332
      controls. Outcomes were favorable in most patients. The main determinants of
      preventable medication-related hospital admissions were impaired cognition (odds
      ratio, 11.9; 95% confidence interval, 3.9-36.3), 4 or more comorbidities (8.1;
      3.1-21.7), dependent living situation (3.0; 1.4-6.5), impaired renal function
      (2.6; 1.6-4.2), nonadherence to medication regimen (2.3; 1.4-3.8), and
      polypharmacy (2.7; 1.6-4.4). CONCLUSIONS: Adverse drug events are an important
      cause of hospitalizations, and almost half are potentially preventable. The
      identified risk factors provide a starting point for preventing medication
      related hospital admissions.

PMID- 18809817
TI  - Community infections caused by extended-spectrum beta-lactamase-producing
      Escherichia coli.
AB  - BACKGROUND: Extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli is
      an increasingly important group of community pathogens worldwide. These organisms
      are frequently resistant to many of the antimicrobial agents usually recommended
      for the treatment of infections caused by E coli, such as penicillins,
      cephalosporins, fluoroquinolones, and trimethoprim-sulfamethoxazole. Data
      concerning risk factors, clinical features, and therapeutic options for such
      infections are scarce. METHODS: A case-control study was performed to investigate
      the risk factors for all types of community-acquired infections caused by ESBL
      producing E coli in 11 Spanish hospitals from February 2002 to May 2003. Controls
      were randomly chosen from among outpatients with a clinical sample not yielding
      ESBL-producing E coli. The clinical features of these infections were
      investigated in the case patients. The efficacy of fosfomycin tromethamine and
      amoxicillin-clavulanate potassium was observationally studied in patients with
      cystitis. RESULTS: A total of 122 cases were included. Risk factors selected by
      multivariate analysis included the following: age older than 60 years; female
      sex; diabetes mellitus; recurrent urinary tract infections (UTIs); previous
      invasive procedures of the urinary tract; follow-up in outpatient clinic; and
      previous receipt of aminopenicillins, cephalosporins, and fluoroquinolones.
      Urinary tract infections accounted for 93% of the cases; 6% of the patients were
      bacteremic and 10% needed hospitalization. The cure rate of patients with
      cystitis was 93% with fosfomycin therapy (all isolates were susceptible); among
      patients treated with amoxicillin-clavulanate, cure rates were 93% for those with
      susceptible isolates (minimum inhibitory concentration < or =8 microg/mL) and 56%
      for those with intermediate or resistant isolates (minimum inhibitory
      concentration > or =16 microg/mL) (P = .02). CONCLUSIONS: In predisposed
      patients, ESBL-producing E coli is a notable cause of community-acquired
      infection, and particularly UTI. Fosfomycin and amoxicillin-clavulanate appear to
      be effective for cystitis caused by susceptible isolates.

PMID- 18809818
TI  - Chronic immune stimulation and subsequent Waldenstrom macroglobulinemia.
AB  - BACKGROUND: Certain autoimmune and infectious conditions are associated with
      increased risks of subtypes of non-Hodgkin lymphoma. A few previous studies
      suggest that chronic inflammation may particularly elevate risk of the distinct
      non-Hodgkin lymphoma subtype Waldenstrom macroglobulinemia (WM). METHODS: We
      assessed WM risk in relation to a variety of chronic immune stimulatory
      conditions in 4 million US veterans. We identified 361 patients with WM with up
      to 27 years of follow-up. Using time-dependent Poisson regression, we estimated
      rate ratios (RRs) and 95% confidence intervals (CIs) for WM risk in relation to
      history of autoimmune diseases that typically have autoantibodies (with systemic
      or organ involvement) or do not have autoantibodies, infections, and allergies.
      All the models were adjusted for attained age, calendar year, race, number of
      hospital visits, and latency between study entry and exit. RESULTS: The age
      standardized incidence of WM was 0.34 per 100,000 person-years. Risk of WM was
      elevated in individuals with any previous autoimmune condition (RR, 2.23; 95% CI,
      1.68-2.97), autoantibodies with systemic involvement (2.50; 1.55-4.02), or
      autoantibodies with organ involvement (2.30; 1.57-3.37). Risks of WM were also
      increased with hepatitis (RR, 3.39; 95% CI, 1.38-8.30), human immunodeficiency
      virus (12.05; 2.83-51.46), and rickettsiosis (3.35; 1.38-8.14). CONCLUSIONS: In
      the largest investigation of WM risk factors to date, we found a 2- to 3-fold
      elevated risk of WM in persons with a personal history of autoimmune diseases
      with autoantibodies and notably elevated risks associated with hepatitis, human
      immunodeficiency virus, and rickettsiosis. These findings provide novel insights
      into the still unknown etiology of WM.

PMID- 18809820
TI  - Signposts along the NIH roadmap for reengineering clinical research: lessons from
      the Clinical Research Networks initiative.
AB  - BACKGROUND: The National Institutes of Health (NIH) Roadmap for Medical Research
      aims to increase the efficiency and speed of clinical research. We report results
      and lessons learned from a key component of the Roadmap, the Clinical Research
      Networks initiative. METHODS: Twelve diverse, experienced, large, clinical
      research networks were funded for 3 years to develop strategies for integrating,
      expanding, and increasing the interoperability of clinical research networks in
      support of the Roadmap goals. Network leaders met periodically in person and by
      teleconference to describe common challenges encountered and solutions used for
      expansion and increased interoperability. RESULTS: These networks developed
      innovative solutions to technical challenges, including strategies for
      interoperability of information systems and management of complex information
      system technologies (eg, "brokering" to address data system incompatibility, data
      transfer, and security requirements), and solutions to human factor challenges at
      the individual, group, intraorganizational, and interorganizational levels (eg,
      applying collaborative organizing and decision-making processes based on key
      principles). CONCLUSIONS: These solutions can provide guidance to existing and
      future clinical research networks, particularly those forming as part of the NIH
      Clinical Translation Science Award program. Remaining technical and human factor
      challenges, however, as well as the largely unmet need for consistent funding for
      network infrastructure and maintenance, stand in the way of fulfilling the vision
      of a robust future role for clinical research networks.

PMID- 18809819
TI  - Cost-effectiveness of HIV monitoring strategies in resource-limited settings: a
      southern African analysis.
AB  - BACKGROUND: Although the number of infected persons receiving highly active
      antiretroviral therapy (HAART) in low- and middle-income countries has increased
      dramatically, optimal disease management is not well defined. METHODS: We
      developed a model to compare the costs and benefits of 3 types of human
      immunodeficiency virus monitoring strategies: symptom-based strategies, CD4-based
      strategies, and CD4 counts plus viral load strategies for starting, switching,
      and stopping HAART. We used clinical and cost data from southern Africa and
      performed a cost-effectiveness analysis. All assumptions were tested in
      sensitivity analyses. RESULTS: Compared with the symptom-based approaches,
      monitoring CD4 counts every 6 months and starting treatment at a threshold of
      200/muL was associated with a gain in life expectancy of 6.5 months (61.9 months
      vs 68.4 months) and a discounted lifetime cost savings of US $464 per person (US
      $4069 vs US $3605, discounted 2007 dollars). The CD4-based strategies in which
      treatment was started at the higher threshold of 350/microL provided an
      additional gain in life expectancy of 5.3 months at a cost-effectiveness of US
      $107 per life-year gained compared with a threshold of 200/microL. Monitoring
      viral load with CD4 was more expensive than monitoring CD4 counts alone, added
      2.0 months of life, and had an incremental cost-effectiveness ratio of US $5414
      per life-year gained relative to monitoring of CD4 counts. In sensitivity
      analyses, the cost savings from CD4 count monitoring compared with the symptom
      based approaches was sensitive to cost of inpatient care, and the cost
      effectiveness of viral load monitoring was influenced by the per test costs and
      rates of virologic failure. CONCLUSIONS: Use of CD4 monitoring and early
      initiation of HAART in southern Africa provides large health benefits relative to
      symptom-based approaches for HAART management. In southern African countries with
      relatively high costs of hospitalization, CD4 monitoring would likely reduce
      total health care expenditures. The cost-effectiveness of viral load monitoring
      depends on test prices and rates of virologic failure.

PMID- 18809821
TI  - Triple-class antiretroviral agent resistance in a large cohort: prevalence and
      clinical outcomes.

PMID- 18809822
TI  - Methotrexate is not associated with progression of interstitial lung disease in
      rheumatoid arthritis.

PMID- 18809823
TI  - Medication nonadherence for blood pressure control is primarily a physician
      related factor.

PMID- 18809824
TI  - Importance of perception for blood pressure control.

PMID- 18809825
TI  - Measures of drug toxicity in older adults.

PMID- 18809826
TI  - Association of snoring with chronic bronchitis.

PMID- 18809827
TI  - Factors in warfarin therapy discontinuation.

PMID- 18809828
TI  - Warfarin therapy adjustment for oral surgery is an unnecessary risk.

PMID- 18809830
TI  - Teaching NeuroImage: posttraumatic palatal tremor.

PMID- 18809832
TI  - Into the looking glass: predicting MS in children experiencing a first
      demyelinating event.

PMID- 18809833
TI  - Distinct CSF cytokine/chemokine profiles in atopic myelitis and other causes of
      myelitis.
AB  - BACKGROUND: We reported the emergence of a distinct myelitis in patients with
      atopic diathesis (atopic myelitis [AM]) by a nationwide survey throughout Japan.
      Similar cases have recently been reported in Caucasians. Pathologic studies of
      biopsied spinal cord specimens revealed chronic active inflammation with
      eosinophilic infiltration. OBJECTIVE: To clarify the cytokine/chemokine
      alterations in CSF from patients with AM in comparison to other causes of
      myelitis. METHODS: We measured 27 cytokines, chemokines, and growth factors
      simultaneously in CSF from 22 patients with AM, 20 with opticospinal multiple
      sclerosis (OSMS), 11 with HTLV-1-associated myelopathy (HAM), 9 with Sjogren
      syndrome-related myelitis (SM), and 20 with other noninflammatory neurologic
      diseases (OND), using a fluorescent bead-based immunoassay. RESULTS: In patients
      with AM, CCL11 and interleukin (IL)-9 were significantly increased as compared
      with patients with OND and other myelitis while in patients with OSMS interferon
      gamma and granulocyte-colony stimulating factor levels were significantly higher
      than in patients with OND and other causes of myelitis. Significant increase of
      IL-17 in comparison to patients with OND was found only in patients with OSMS,
      irrespective of presence or absence of anti-aquaporin-4 (AQP4) antibody. In
      patients with HAM, CXCL10 and CCL5 were higher than in patients with OND and
      other myelitis. In patients with SM, CCL3 and CCL4 were higher than in patients
      with OND. In patients with AM, CCL11, IL-9, and IL-1 receptor antagonist (IL-1ra)
      showed positive correlations with the final Kurtzke Expanded Disability Status
      Scale scores while IL-1ra and IL-12(p70) had positive correlations with disease
      duration. CONCLUSION: Intrathecal upregulation of CCL11 and Th2 cytokines is
      characteristic of atopic myelitis, which is distinct from interleukin
      17/interferon-gamma-related autoimmune condition of opticospinal multiple
      sclerosis.

PMID- 18809834
TI  - Influence of magnetic source imaging for planning intracranial EEG in epilepsy.
AB  - BACKGROUND: Magnetic source imaging (MSI) is used routinely in epilepsy
      presurgical evaluation and in mapping eloquent cortex for surgery. Despite
      increasing use, the diagnostic yield of MSI is uncertain, with reports varying
      from 5% to 35%. To add benefit, a diagnostic technique should influence decisions
      made from other tests, and that influence should yield better outcomes. We report
      preliminary results of an ongoing, long-term clinical study in epilepsy, where
      MSI changed surgical decisions. METHODS: We determined whether MSI changed the
      surgical decision in a prospective, blinded, crossover-controlled, single
      treatment, observational case series. Sixty-nine sequential patients diagnosed
      with partial epilepsy of suspected neocortical origin had video-EEG and imaging.
      All met criteria for intracranial EEG (ICEEG). At a surgical conference, a
      decision was made before and after presentation of MSI. Cases where MSI altered
      the decision were noted. RESULTS: MSI gave nonredundant information in 23
      patients (33%). MSI added ICEEG electrodes in 9 (13%) and changed the surgical
      decision in another 14 (20%). Based on MSI, 16 patients (23%) were scheduled for
      different ICEEG coverage. Twenty-eight have gone to ICEEG, 29 to resection, and
      14 to vagal nerve stimulation, including 17 where MSI changed the decision.
      Additional electrodes in 4 patients covered the correct: hemisphere in 3, lobe in
      3, and sublobar ictal onset zone in 1. MSI avoided contralateral electrodes in 2,
      who both localized on ICEEG. MSI added information to ICEEG in 1. CONCLUSION:
      Magnetic source imaging (MSI) provided nonredundant information in 33% of
      patients. In those who have undergone surgery to date, MSI added useful
      information that changed treatment in 6 (9%), without increasing complications.
      MSI has benefited 21% who have gone to surgery.

PMID- 18809835
TI  - CDKL5 mutations in boys with severe encephalopathy and early-onset intractable
      epilepsy.
AB  - OBJECTIVE: To search for CDKL5 gene mutations in boys presenting with severe
      early-onset encephalopathy and intractable epilepsy, a clinical picture very
      similar to that already described in girls with CDKL5 mutations. METHODS: Eight
      boys (age range 3-16 years, mean age 8.5 years, SD 4.38) with severe or profound
      mental retardation and early-onset intractable seizures were selected for CDKL5
      gene mutation screening by denaturing high-performance liquid chromatography
      analysis. RESULTS: We found three unrelated boys carrying three different
      missense mutations of the CDKL5 gene: c.872G>A (p.C291Y), c.863C>T (p.T288I), and
      c.533G>C (p.R178P). They presented early-onset, polymorphous, and drug-resistant
      seizures, mostly myoclonic and tonic or spasms. EEG showed epileptiform
      abnormalities which were multifocal during wakefulness, and pseudoperiodic
      bisynchronous during sleep. CONCLUSIONS: This study describes three boys carrying
      CDKL5 missense mutations and their detailed clinical and EEG data, and indicates
      that CDKL5 gene mutations may represent a cause of severe or profound mental
      retardation and early-onset intractable seizures, also in boys. Screening for
      CDKL5 mutations is strongly recommended in individuals with these clinical
      features.

PMID- 18809836
TI  - Predictors of antecedent factors in psychogenic nonepileptic attacks:
      multivariate analysis.
AB  - OBJECTIVES: To elucidate the role of antecedent factors in psychogenic
      nonepileptic attacks (PNEA). METHODS: In a consecutive series of 288 patients
      with PNEA, clinical and demographic variables were entered into binary logistic
      regression models and tested for their power to predict commonly reported
      antecedent factors. RESULTS: Three quarters (75.4%) of patients reported
      traumatic antecedent factors: 32.5% reported sexual abuse, 26.0% physical abuse,
      18.7% bereavement, 8.3% health-related trauma, and 8% accident or assault. A
      total of 8.6% had learning disability (LD) and 10.8% had epilepsy. Antecedent
      trauma in general was predicted by later age at onset (p = 0.011), and medically
      unexplained symptoms (MUS) other than PNEA (p = 0.004); its absence was predicted
      by LD (p = 0.016). Sexual abuse was predicted by female gender (p < 0.001),
      physical abuse (p < 0.001), self-harm (p < 0.001), and MUS (p < 0.001): its
      absence was predicted by LD (p = 0.019) and health-related trauma (p = 0.023).
      Bullying was predicted by early onset of PNEA (p = 0.012). Health-related trauma
      was predicted by late age at onset (p < 0.001); its absence was predicted by
      sexual abuse (p = 0.020). LD was predicted by male gender (p = 0.019), epilepsy
      (p = 0.005), circumstantial triggering of spells (p < 0.001), and pseudostatus (p
      = 0.012). Epilepsy was predicted by LD (p = 0.001) and early age at onset (p =
      0.013). CONCLUSIONS: The clinical predictors that we found provide further
      evidence of heterogeneity of psychogenic nonepileptic attacks populations related
      to antecedent factors. Some predictive clusters may have clinical utility in the
      early stages of assessment: in particular the combination of medically
      unexplained symptoms and self-harm should raise the possibility of undisclosed
      sexual abuse.

PMID- 18809837
TI  - Vestibular paroxysmia: diagnostic features and medical treatment.
AB  - BACKGROUND: Vestibular paroxysmia (VP), which is attributed to neurovascular
      cross-compression (NVCC), leads to vertiginous spells. Although VP was described
      more than 30 years ago by Jannetta and colleagues, we still need more reliable
      data on its diagnostic features and the efficacy of medical treatment. METHODS: A
      follow-up study of 32 patients with recurrent short spells of vertigo and with
      diagnosis of VP by published criteria was performed using medical records and
      patient consultation (mean follow-up time 31.3 months). RESULTS: In 28% of
      patients the attacks occurred exclusively when at rest, whereas in 22% they were
      regularly precipitated by a certain action, most frequently a head turn (60%).
      The most common accompanying symptom was unsteadiness of stance or gait (75%).
      Constructive interference in steady state magnetic resonance imaging (n = 23)
      demonstrated at least one site of NVCC in all but one patient. Caloric testing
      disclosed a mild increase in vestibular deficit over time, and a hyperventilation
      induced nystagmus was found in 70% of the tested patients (n = 23). The majority
      of patients were treated with carbamazepine (mean dose 568 mg/d) or oxcarbazepine
      (mean dose 870 mg/d). Treatment led to a significant reduction in the attack
      frequency to 10% of baseline (95% CI 6.69-14.96%), in attack intensity to 15%
      (95% CI 11.57-19.63%), and a reduction in attack duration to 11% (95% CI 6.72
      17.40), after adjusting for time effects. CONCLUSION: This follow-up proves the
      usefulness of the diagnostic criteria, especially constructive interference in
      steady state magnetic resonance imaging, and the therapeutic efficacy of medical
      treatment.

PMID- 18809838
TI  - Familiality in brain tumors.
AB  - BACKGROUND: Familiality in brain tumors is not definitively substantiated.
      METHODS: We used the Utah Population Data Base (UPDB), a genealogy representing
      the Utah pioneers and their descendants, record-linked to statewide cancer
      records, to describe the familial nature of primary brain cancer. We examined the
      familial clustering of primary brain tumors, including subgroups defined by
      histologic type and age at diagnosis. The UPDB includes 1,401 primary brain tumor
      cases defined as astrocytoma or glioblastoma, all with at least three generations
      of genealogy data. We tested the hypothesis of excess relatedness of brain tumor
      cases using the Genealogical Index of Familiality method. We estimated relative
      risks for brain tumors in relatives using rates of brain tumors estimated
      internally. RESULTS: Significant excess relatedness was observed for astrocytomas
      and glioblastomas considered as a group (n = 1,401), for astrocytomas considered
      separately (n = 744), but not for glioblastomas considered separately (n = 658).
      Significantly increased risks to first- and second-degree relatives for
      astrocytomas were identified for relatives of astrocytomas considered separately.
      Significantly increased risks to first-degree relatives, but not second degree,
      were observed for astrocytoma and glioblastoma cases considered together, and for
      glioblastoma cases considered separately. CONCLUSIONS: This study provides strong
      evidence for a familial contribution to primary brain cancer risk. There is
      evidence that this familial aspect includes not only shared environment, but also
      a heritable component. Extended high-risk brain tumor pedigrees identified in the
      UPDB may provide the opportunity to identify predisposition genes responsible for
      familial brain tumors.

PMID- 18809839
TI  - Hyposmia in G2019S LRRK2-related parkinsonism: clinical and pathologic data.
AB  - BACKGROUND: Mutations in PARK8 (LRRK2) are associated with autosomal dominant
      parkinsonism and Parkinson disease (PD). Hyposmia is present in at least 80% of
      patients with PD and an accumulation of alpha-synuclein (alpha-syn) is seen in
      the olfactory pathways. In this study we have clinically examined olfaction and
      pathologically examined the rhinencephalon in individuals carrying the G2019S
      LRRK2 mutation. METHODS: The University of Pennsylvania Smell Test (UPSIT) was
      used to evaluate the sense of smell in 19 parkinsonian and two asymptomatic
      carriers of the G2019S mutation and compared with groups of patients with PD and
      healthy controls. Postmortem examination of alpha-syn accumulation in the
      rhinencephalon was also carried out in four parkinsonian carriers of the G2019S
      mutation. RESULTS: The mean UPSIT score in G2019S parkinsonian carriers was lower
      than that in healthy controls (p < 0.001) and similar to that found in patients
      with PD (p > 0.999). Smell tests in two asymptomatic carriers of the G2019S
      mutation were in the normal range. Postmortem studies of the olfactory pathways
      in one of the patients who had been clinically tested, and found to have
      hyposmia, and three other cases with the G2019S mutation, revealed alpha-syn
      deposition in the olfactory pathways in all cases. CONCLUSIONS: Odor
      identification is diminished in LRRK2 G2019S mutation parkinsonism but the
      asymptomatic carriers of the mutation had normal olfaction. We found alpha-syn
      accumulation with Lewy bodies in the rhinencephalon in all four cases examined
      pathologically.

PMID- 18809840
TI  - Broadened and elevated humoral immune response to EBNA1 in pediatric multiple
      sclerosis.

PMID- 18809841
TI  - Two sets of identical twins with cervical artery dissection concordant for
      temporal artery pathology.

PMID- 18809842
TI  - Reflections: neurology and the humanities. Developmental arrest.

PMID- 18809843
TI  - Mesencephalic bilateral horizontal gaze palsies.

PMID- 18809844
TI  - Neutralizing antibodies in dystonic patients who still respond well to botulinum
      toxin type A.

PMID- 18809845
TI  - Rhinorrhea and olfaction in Parkinson disease.

PMID- 18809846
TI  - Intersections of harm and health: a qualitative study of intimate partner
      violence in women's lives.
AB  - Eight focus groups of women with recent exposure to intimate partner violence
      (IPV) were conducted to elicit women's descriptions of how IPV affects their
      health. Their shared narratives reveal a complex relationship with three main
      points of intersection between IPV and health: IPV leading to adverse health
      effects; IPV worsening already compromised health; and women's illness or
      disability increasing dependency on abusive partners, thereby lengthening the
      duration of IPV exposure. Women describe bidirectional and cyclical ways through
      which IPV and health intersect over time. Service providers, including
      physicians, need to better understand the myriad ways that abuse affects women's
      health.

PMID- 18809847
TI  - Danger zone: battered mothers and their families in supervised visitation.
AB  - Supervised visitation centers (SVCs) have developed rapidly across the United
      States. Increasingly, courts are restricting contact between abusive intimate
      partners and their children by ordering visitation or exchanges to occur at SVCs.
      This article describes some of the key lessons the authors learned over 18 months
      of planning and then another 18 months of implementation at a SVC developed
      specifically to serve families for whom domestic violence was their primary
      reason for referral. The authors have organized their experiences around five
      major themes: (a) battered women in supervised visitation, (b) how battering
      continues during supervised visitation, (c) how rules at the SVC evolved over the
      first 18 months of implementation, (d) the importance of well-trained visit
      monitors, and (e) the need to embed SVCs within a larger context of coordinated
      community responses to domestic violence.

PMID- 18809848
TI  - Understanding violence against Chinese women in Hong Kong: an analysis of risk
      factors with a special emphasis on the role of in-law conflict.
AB  - This study examines risk factors of intimate partner violence against women in a
      cohort of Chinese women drawn from a large representative sample in Hong Kong.
      Data from a cross-section of 1,870 women are analyzed. Prevalence rates of
      women's self-reports of violence by their intimate partners and conflict with in
      laws are computed and compared in terms of demographic and socioeconomic
      characteristics. The results show that in-law conflict was the characteristic
      most significantly associated with women's reports of violent victimization. This
      suggests that in-law conflict should be included in the screening and assessment
      of risk for intimate partner violence.

PMID- 18809849
TI  - Combining ethical considerations with recruitment and follow-up strategies for
      partner violence victimization research.
AB  - In general, the literature on research ethics and the literature on recruitment
      and retention of research participants tend to be separated by different purposes
      and principles. This article uses multiple methods to compile information about
      research ethics with vulnerable participants as well as with recruitment and
      follow-up strategies, including (a) literature reviews, (b) key informant
      interviews, (c) focus group interviews, (d) a pilot study to test ideas for study
      implementation, and (e) documentation of recruitment and follow-up efforts for a
      longitudinal study of 757 women with partner violence victimization experiences.
      This article shows how considering research ethics may actually enhance
      recruitment and follow-up strategies with women experiencing partner violence
      victimization.

PMID- 18809850
TI  - Computational models explain the oligosaccharide specificity of cyanovirin-N.
AB  - The prokaryotic lectin cyanovirin-N (CV-N) is a potent inhibitor of HIV envelope
      mediated cell entry, and thus is a leading candidate among a new class of
      potential anti-HIV microbicides. The activity of CV-N is a result of interactions
      with the D1 arm of high-mannose oligosaccharides on the viral glycoprotein gp120.
      Here, we present computationally refined models of CV-N recognition of the di-
      and trisaccharides that represent the terminal three sugars of the D1 arm by each
      CV-N binding site. These models complement existing structural data, both from
      NMR spectroscopy and X-ray crystallography. When used with a molecular
      dynamics/continuum electrostatic (MD/PBSA) approach to compute binding free
      energies, these models explain the relative affinity of each site for the two
      saccharides. This work presents the first validation of the application of
      continuum electrostatic models to carbohydrate-protein association. Taken as a
      whole, the results both provide models of CV-N sugar recognition and demonstrate
      the utility of these computational methods for the study of carbohydrate-binding
      proteins.

PMID- 18809851
TI  - Structural requirements for calmodulin binding to membrane-associated guanylate
      kinase homologs.
AB  - Effector molecules such as calmodulin modulate the interactions of membrane
      associated guanylate kinase homologs (MAGUKs) and other scaffolding proteins of
      the membrane cytoskeleton by binding to the Src homology 3 (SH3) domain, the
      guanylate kinase (GK) domain, or the connecting HOOK region of MAGUKs. Using
      surface plasmon resonance, we studied the interaction of members of all four
      MAGUK subfamilies--synapse-associated protein 97 (SAP97), calcium/calmodulin
      dependent serine protein kinase (CASK), membrane palmitoylated protein 2 (MPP2),
      and zona occludens (ZO) 1--and calmodulin to determine interaction affinities and
      localize the binding site. The SH3-GK domains of the proteins and derivatives
      thereof were expressed in E. coli and purified. In all four proteins, high
      affinity calmodulin binding was identified. CASK was shown to contain a Ca2+
      dependent calmodulin binding site within the HOOK region, overlapping with a
      protein 4.1 binding site. In ZO1, a Ca2+-dependent calmodulin binding site was
      detected within the GK domain. The equilibrium dissociation constants for MAGUK
      calmodulin interaction were found to range from 50 nM to 180 nM. Sequence
      analyses suggest that binding sites for calmodulin have evolved independently in
      at least three subfamilies. For ZO1, pulldown of GST-calmodulin was shown to
      occur in a calcium-dependent manner; moreover, molecular modeling and sequence
      analyses predict conserved basic residues to be exposed on one side of a helix.
      Thus, calmodulin binding appears to be a common feature of MAGUKs, and Ca2+
      activated calmodulin may serve as a general regulator to affect the interactions
      of MAGUKs and various components of the cytoskeleton.

PMID- 18809852
TI  - Absolute and relative standards--the case of leptin in poultry: first do no harm.

PMID- 18809853
TI  - A review of the capacity for nutritional strategies to address environmental
      challenges in poultry production.
AB  - Poultry production faces increasing environmental challenges, in the United
      States and globally. Although the environmental impact of poultry production has
      been decreased, regulatory and social pressures mandate that further improvements
      be made to decrease the pollution potential even more. Concerns over air and
      water quality to date have been related primarily to nutrient issues,
      specifically N and P. Air emission concerns include N and sulfur emissions. More
      recently, states have addressed emissions of volatile organic compounds. Although
      no regulations have been developed that are targeted at food production,
      greenhouse gas emissions are receiving a great deal of attention in the United
      States. Nutrient-related water quality concerns have focused on N and P
      contributions to ground and surface waters, respectively. To address nutrient
      related air and water quality concerns, nutritional strategies have focused on
      reducing nutrient excretions. These strategies have been very successful.
      However, strategies beyond just reducing nutrient excesses will be needed to meet
      future challenges that are not nutrient-related. Challenges such as pathogens,
      antimicrobials, and endocrine-disrupting compounds have received considerable
      attention recently. The purpose of this review is to provide an overview of the
      findings from nutrition research with respect to reducing environmental impact
      and to identify areas that merit attention in the near future, recognizing that
      many of the emerging environmental issues are not nutrient-related.

PMID- 18809854
TI  - Appearance matters: artificial marking alters aggression and stress.
AB  - Artificial marking of animals for identification is frequently employed by
      researchers in the behavioral, biomedical, agricultural, and environmental
      sciences. The impact of artificial marking on experimental results is rarely
      explicitly considered despite evidence demonstrating that changes in phenotypic
      appearance can modify animal behavior and reproductive success. Here we present
      evidence that artificial marking of individuals within a social group has
      frequency-dependent effects on the behavior and physiology of domestic fowl
      (Gallus gallus domesticus). We demonstrate that when only 20 or 50% of
      individuals within a group were artificially marked, the marked birds received
      more aggression and had lesser body mass than the unmarked individuals within the
      same group. Furthermore, in groups in which only a small proportion of the
      individuals were marked, we report altered plasma epinephrine and dopamine levels
      in marked individuals. These effects of marking were imperceptible when all birds
      in a group were marked. This finding has important implications for animal
      research because, when only a subset of group members is artificially marked and
      used for data collection, the results obtained may not be representative of the
      population.

PMID- 18809855
TI  - Effects of social disruption on physical parameters, corticosterone
      concentrations, and immune system in two genetic lines of White Leghorn layers.
AB  - Farm management practices such as increasing group size and mixing of unfamiliar
      chickens may cause social disruption and affect bird well-being. To examine
      genetic-associated physical and physiological differences in response to social
      disruption, 2 strains of White Leghorn hens were used in the study [i.e., HGPS
      (line selected for high group production and survivability) and DXL (DeKalb XL
      commercial line)]. Social disruption was created when hens were 50 wk of age by
      increasing group size from 4 hens (control) to 8 hens (experimental) per cage and
      providing an unstable social environment by moving 2 hens weekly between cages
      within the same line (experimental hens only). At 58 wk of age, hens were feather
      scored. After euthanization, BW and the right adrenal gland weight were collected
      (n = 10 per treatment). Adrenal gland weight was adjusted for BW, and adjusted
      adrenal weight was used for analysis. Plasma corticosterone was quantified using
      RIA. The T-lymphocytes (CD4+ and CD8+) were measured using flow cytometry.
      Results showed that average feather cover score was greater for DXL hens than
      HGPS hens in both the unstressed (P < 0.05) and stressed treatment (P < 0.01).
      There was no difference in BW in DXL and HGPS hens between the control and the
      social disruption treatments. However, the relative adrenal weight of HGPS hens
      tended to be lower than control hens after social disruption (0.05 > P < 0.10).
      Plasma corticosterone was significantly lower in both strains following social
      disruption (P < 0.01). The T-lymphocyte ratio (CD4+:CD8+) was greater in HGPS
      hens than DXL hens post social disruption (P < 0.05). The data indicate that the
      2 strains of hens reacted differently in terms of the adrenal system and immunity
      in response to social disruption. Hens selected for longevity with docile
      behaviors and high productivity, such as HGPS hens, provide a useful tool for
      improving animal well-being.

PMID- 18809856
TI  - Effects of liquid aluminum chloride additions to poultry litter on broiler
      performance, ammonia emissions, soluble phosphorus, total volatile Fatty acids,
      and nitrogen contents of litter.
AB  - Recent studies have shown that the use of aluminum sulfate [alum,
      Al2(SO4)3.14H2O] and aluminum chloride (AlCl3) additions to animal manures are
      more effective than other chemicals in reducing ammonia (NH3) emissions and P
      solubility. Although the use of Al2(SO4)3.14H2O has been intensively used in the
      poultry industry for many years, no research has been conducted to evaluate the
      effect of liquid AlCl3 on these parameters. The objectives of this study were to
      determine the effects of applying liquid AlCl3 to poultry litter on 1) broiler
      performance, 2) NH3 fluxes, and 3) litter chemical characteristics, including
      soluble reactive P, total volatile fatty acids, and N content. Eight hundred
      broiler chicks were placed into 16 floor pens (50 birds/pen) in a single house
      for 6 wk. Liquid AlCl3 treatments were sprayed on the litter surface at rates of
      100, 200, and 300 g of liquid AlCl3/kg of litter; un-treated litter served as
      controls. At the 2 lower rates, liquid AlCl3 treatments tended to improve weight
      gain and feed intake but had no effect on feed conversion or mortality, whereas
      the higher rate (300 g/kg of litter) had a negative effect on intake. Application
      of 100, 200, and 300 g of liquid AlCl3 reduced NH3 fluxes by 63, 76, and 76%
      during the 6-wk period, respectively, compared with the controls. Liquid AlCl3
      additions reduced litter soluble reactive P contents by 24, 30, and 36%,
      respectively, at the low, medium, and high rates. Total volatile fatty acid
      contents (odor precursors) in litter were reduced by 20, 50, and 51%,
      respectively, with 100, 200, and 300 g of liquid AlCl3/kg of litter. Liquid AlCl3
      additions increased total N, inorganic N, and plant available N contents in
      litter. These results indicate that liquid AlCl3 additions at the lower rates can
      provide significant positive environmental benefits to broiler operations.

PMID- 18809857
TI  - Bone fracture incidence in end-of-lay high-producing, noncommercial laying hens
      identified using radiographs.
AB  - Bone fractures in laying hens are both a welfare and an economic concern for the
      poultry industry. The aim of this study was to use radiographs to quantify
      fracture incidence in 6 lines of noncommercial high-producing laying hens. A
      total of 451 hens (n = 71 to 78) were killed at 47 wk (White Leghorn-Black, White
      Leghorn-Blue) or 65 wk of age [Barred Plymouth Rock (BR), White Leghorn-Burgundy
      (WL-BUR), Columbian Plymouth Rock, Rhode Island Red (RIR)]. Radiographs were
      obtained with hens in 2 positions (lateral and ventrodorsal) and were used to
      identify fractures in the skeleton. Data on scallop-shaped indentations (possibly
      fractures) of the keel bone were also collected. After radiography, the left
      wings were removed for analysis of humeri, radii, and ulnae. Data for the 2 age
      groups were analyzed separately. The overall incidence of hens with at least 1
      fracture was 6.6 and 15.7% in the 47- and 65-wk-old hens, respectively. Fracture
      incidence in 47-wk-old hens was not different between White Leghorn-Black and
      White Leghorn-Blue lines. Significant line differences were observed in the 65-wk
      old hens, with at least 1 fracture found in 29.5% of RIR hens versus 9.5 and 4.2%
      observed in Columbian Plymouth Rock and WL-BUR lines, respectively. Fracture
      incidence in BR hens (18.2%) was greater than in WL-BUR hens. Fractures in RIR
      hens occurred predominantly in the furculum and wing bones, whereas pubic bones
      were most affected in BR hens. The proportion of hens with scallop-shaped
      indentations of the keel ranged from 36.1 to 88.2% and differed between lines in
      both age groups. High egg production did not seem to be associated with bone
      fragility in these lines. Two of the older lines (RIR and WL-BUR) had similar egg
      production, number of eggs to 60 wk, and egg shell weights at 4 ages but had a
      significantly different fracture incidence. The line differences in fracture
      incidence may have been affected by calcium metabolism, bone structure, and body
      weight.

PMID- 18809858
TI  - Genetics of growth and reproduction in the Turkey. 17. Changes in genetic
      parameters over forty generations of selection for increased sixteen-week body
      weight.
AB  - A line (F) of turkeys was selected over 40 generations for increased 16-wk BW.
      The base population for the F line was a randombred control population that was
      maintained without conscious selection and used to remove yearly environmental
      variation in the F line. Selection was effective in increasing 16-wk BW in the F
      line. Selection differentials based on the mean of the selected parents minus the
      mean of the entire population (intended) and intended selection differentials
      weighted for number of offspring produced (actual) did not differ consistently,
      indicating that natural selection was not opposing artificial selection during
      the reproduction of the F line. The realized heritability of 16-wk BW in the F
      line, based on the linear regression of the selection response on accumulated
      actual selection differential, declined with selection. For both sexes combined,
      the realized heritability was 0.309 +/- 0.022 (SE), 0.268 +/- 0.033, 0.268 +/-
      0.026, 0.166 +/- 0.016, and 0.242 +/- 0.004, respectively, for generations 1 to
      10, 11 to 20, 21 to 30, 31 to 40, and 1 to 40. Genetic increases in 16-wk BW in
      the F line over 40 generations of selection were positively associated with BW at
      other ages (8 and 20 wk of age and at 50% production), shank length and width at
      16 wk of age, days from stimulatory lighting to production of the first egg, and
      egg weight but were negatively associated with egg production, intensity of lay
      (maximum and average clutch length and rate of lay), and walking ability. Over
      the 40 generations of selection, genetic increases in BW in the F line were not
      associated with changes in broodiness or mortality to 8 wk of age. During
      generations 31 to 40, BW at 8 and 20 wk of age continued to increase in the F
      line, but there was no significant change in adult BW, and the only significant
      change in reproduction traits was for average clutch length (-0.030). Because the
      genetic changes in some correlated traits were not consistent in all generation
      intervals studied, the genetic correlation between the selected trait (16-wk BW)
      and the correlated trait apparently changed with selection.

PMID- 18809859
TI  - The effect of site-directed mutagenesis of the ambient amino acids of leucine
      based sorting motifs on the localization of chicken invariant chain.
AB  - Two Leu residues and their ambient amino acid residues are known to exist in the
      cytosolic tail of chicken invariant chain (Ii), and these play an important role
      as motifs in mediating the sorting endocytic pathway. We performed 20 mutations
      via site-directed mutagenesis by the PCR megaprimer method to study the effect of
      some ambient amino residues of both Leu on the localization of chicken Ii. These
      mutated fragments were ligated to the vector pEGFP-C1. The recombinant plasmids
      were transiently transfected into COS-7 cells with Lipofectamine 2000.
      Furthermore, the fluorescence of located fusion proteins (green fluorescent
      protein-Ii) was observed with a fluorescence microscope. Our results indicated
      that 2 Leu-based motifs are required for chicken Ii intracellular localization,
      and both motifs independently mediate this function of the Ii. The other amino
      acid residues surrounding both Leu also influence Ii-induced endosomal
      vacuolation. In addition, we found that Pro19, which is near the Val17-Leu18
      motif, was a key residue for chicken Ii intracellular localization. Not only is
      it critical for endocytic targeting to each Leu, but its unique mutation can also
      result in altering the function of chicken Ii.

PMID- 18809860
TI  - Risk factors associated with the presence of Campylobacter species in Norwegian
      broiler flocks.
AB  - A case-control study was conducted in 2005 to identify risk factors for the
      presence of Campylobacter spp. in Norwegian broiler flocks. A total of 131
      broiler farms (44 cases and 87 controls) were included in the study, and 1 flock
      from each farm was included in the statistical analyses. Data on farm and flock
      level were collected by means of a questionnaire designed for the present study.
      The relationship and strength of association between the presence of
      Campylobacter spp. in the broiler flocks and several factors were investigated by
      unconditional logistic regression. The following factors were found to be
      associated with an increased risk of testing positive for Campylobacter spp.:
      water from a private water source, swine holdings closer than 2 km, a specific
      slaughterhouse, a hired animal caretaker, transport personnel passing through the
      hygiene barrier when delivering day-old chickens, less than 9 d between
      depopulation and restocking, and multiple broiler houses on the farm.

PMID- 18809861
TI  - Influence of in-feed virginiamycin on the systemic and mucosal antibody response
      of chickens.
AB  - Subtherapeutic and prophylactic doses of virginiamycin are capable of altering
      the intestinal microbiota as well as increasing several growth parameters in
      chickens. In spite of the fact that the microbiota plays a role in shaping the
      host's immune system, little information is available on the effects of in-feed
      antibiotics on the chicken immune system. The objective of this study was to
      examine the effects of an antibiotic, virginiamycin, on the development of
      antibody responses. Chickens were fed diets containing no antibiotics, along with
      either subtherapeutic (11 ppm) or prophylactic (22 ppm) doses of virginiamycin.
      Chickens were then immunized with keyhole limpet hemocyanin (KLH) and sheep red
      blood cells systemically, and with BSA and KLH orally. Although antibodies were
      detected against BSA in the intestinal contents of birds that were orally
      immunized, there was no difference among different treatment groups. Systemic
      IgG, and to a lesser extent IgM, antibody responses to KLH were greater (P <
      0.05) in birds fed a diet containing 11 or 22 ppm of virginiamycin compared with
      control birds fed no antibiotic. No treatment effect was found in the sheep red
      blood cell-immunized birds. Results of the present study implicate virginiamycin
      in enhancing antibody responses to some antigens in chickens. Further studies are
      required to determine to what extent these effects on antibody response are
      mediated through changes in the composition of the microbiota.

PMID- 18809862
TI  - Effects of prelay 6/85-strain Mycoplasma gallisepticum inoculation alone or in
      conjunction with the inoculation of F-strain Mycoplasma gallisepticum during lay
      on the blood characteristics of commercial egg-laying hens.
AB  - The effects of 6/85-strain Mycoplasma gallisepticum (6/85MG) inoculation alone or
      in conjunction with F-strain M. gallisepticum (FMG) overlays and their timing on
      the blood characteristics of commercial egg-laying hens were investigated.
      Control birds received sham inoculations at 10 wk of age. Birds in a second
      treatment group were inoculated with 6/85MG at 10 wk of age, those in a third
      treatment group were inoculated with 6/85MG at 10 wk followed by an overlay
      inoculation of FMG at 22 wk, and those in a fourth treatment group were
      inoculated with 6/85MG at 10 wk followed by an overlay inoculation of FMG at 45
      wk. Parameters investigated at 24, 32, 43, and 47 wk were hematocrit, plasma
      total protein, and serum calcium, triglycerides, and cholesterol. No significant
      treatment effects were noted for hematocrit, serum triglycerides, or serum
      cholesterol. However, at wk 32, plasma protein was greater in birds that received
      6/85MG at 10 wk or 6/85MG at 10 wk and FMG at 22 wk in comparison to controls.
      Also, at wk 47, serum calcium concentration was greater in birds that received
      6/85MG at 10 wk and FMG at 45 wk compared with controls and those that received
      6/85MG at 10 wk and FMG at 22 wk. These results suggest that the prelay
      inoculation of pullets with 6/85MG may subsequently elevate plasma protein, and
      in conjunction with an FMG overlay at 45 wk, may increase serum calcium
      concentrations in laying hens.

PMID- 18809863
TI  - The effect of enzyme supplementation on egg production parameters and omega-3
      fatty acid deposition in laying hens fed flaxseed and canola seed.
AB  - An experiment was conducted to investigate the effects of a multicarbohydrase
      enzyme on egg production parameters, nutrient digestibility, and egg fatty acid
      composition in Hy-Line CV-20 laying hens (39 to 63 wk of age) fed diets
      containing 150 g/kg of diet of canola seed, flaxseed, or Linpro (flaxseed:peas,
      1:1 wt/wt). The diet effect on each parameter was also evaluated. Hens consuming
      the canola seed and Linpro diets had greater egg production, lower feed
      consumption, and therefore better feed conversion than those fed the flaxseed
      diets. Enzyme supplementation significantly increased (P < 0.01) egg production
      (from 78.0 to 80.9%) and improved (P < 0.001) feed conversion ratio (from 2.15 to
      2.03) in hens fed flaxseed. Hens fed the canola seed and Linpro diets produced
      eggs with greater egg specific gravity than those from birds consuming flaxseed.
      Enzyme supplementation significantly increased egg specific gravity in hens fed
      flaxseed (from 1.0773 to 1.0800, P < 0.01) in phase I of the experiment. There
      was no effect of diet on fat digestibility, and similar fat digestibility values
      with enzyme supplementation were observed for canola seed (92.1 vs. 96.7%) and
      flaxseed (87.4 vs. 92.4%). Eggs produced by hens fed flaxseed had the greatest n
      3 fatty acid content (562 mg/60 g of egg) when compared with those from hens
      consuming canola seed (207 mg/60 g of egg) or Linpro (427 mg/60 g of egg). Enzyme
      supplementation increased the egg n-3 content for the flaxseed diet (from 546 to
      578 mg/60 g of egg; P = 0.01) and for the Linpro diet (from 415 to 438 mg/60 g of
      egg; P = 0.05). In addition, enzyme addition increased the egg docosahexaenoic
      acid content from 91.8 to 101.9 mg/60 g of egg (P < 0.01) and from 89.4 to 96.8
      mg/60 g of egg (P = 0.01) for the flaxseed and Linpro diets, respectively. When
      compared with canola seed, long-term feeding of flaxseed to laying hens resulted
      in reduced egg production and eggshell quality. Enzyme supplementation had
      positive effects on feed utilization, eggshell quality, and n-3 fatty acid
      deposition in the egg.

PMID- 18809864
TI  - Corn expressing an Escherichia coli-derived phytase gene: comparative evaluation
      study in broiler chicks.
AB  - The efficacy of corn expressing an Escherichia coli-derived gene (corn-based
      phytase; CBP) and an E. coli-derived microbial phytase (expressed in Pichia
      pastoris) sprayed onto a wheat carrier (Quantum) was comparatively evaluated in
      two 14-d broiler chicken studies. In experiment 1, a total of 288 seven-day-old
      male broiler chicks were grouped by weight into 8 blocks of 6 cages, with 6 birds
      per cage, and used to measure growth performance, bone mineralization, and
      nutrient utilization. In experiment 2, a total of 192 seven-day-old male broiler
      chicks were used, with 4 birds per cage. Six dietary treatment groups were
      randomly allotted to the cages within each of 8 blocks. The corn-soybean meal
      based diets used in each study consisted of a positive control adequate in P and
      Ca; a negative control (NC) low in P and Ca (no added inorganic P); the NC
      supplemented with 3,630, 36,300, or 363,000 phytase units (FTU) of CBP/kg; and
      the NC + 3,630 FTU of Quantum/kg. Growth performance and bone mineralization
      criteria were reevaluated in the second broiler study. Data from the 2
      experiments were combined because there was no diet x experiment interaction and
      analyzed as a randomized complete block design. Weight gain decreased (P < 0.05)
      with a reduction in dietary P and Ca in the NC diet. Weight gain, feed
      efficiency, and percentage of tibia ash of birds fed 3,630 FTU/kg of either CBP
      or Quantum phytase were not different. There was a quadratic response (P < 0.01)
      to CBP supplementation of the NC diets in weight gain of the broiler chicks. Feed
      intake increased quadratically (P < 0.01) with CBP supplementation of the NC
      diets, but CBP supplementation of the NC diets did not affect feed efficiency.
      Tibia ash of birds fed the positive control diet was greater (P < 0.01) than that
      of birds fed the NC diet. There was a quadratic response (P < 0.01) to CBP
      supplementation of the NC diets in tibia ash of the broiler chicks. Birds fed
      supplemental phytase had greater (P < 0.01) ileal and total tract P and Ca
      digestibility than birds fed the NC diet. Data from the study suggest that E.
      coli phytase expressed in corn is efficacious in P-deficient broiler chick diets
      for the improvement of growth performance and indices of P utilization, which
      would minimize the need for supplemental P in broiler diets.

PMID- 18809865
TI  - Meta-analysis of the relative efficiency of methionine-hydroxy-analogue-free-acid
      compared with DL-methionine in broilers using nonlinear mixed models.
AB  - The purpose of this paper was to perform a meta-analysis to compare the
      biological efficiency of DL-methionine with methionine-hydroxy-analogue-free-acid
      in broiler chickens. A database was developed which contained dose-response
      studies of these 2 methionine sources. Criteria for entry into the database were
      defined before the meta-analysis was initiated. Data from 46 dose-response
      experiments, extracted from a total of 27 peer-reviewed papers, were used for the
      analysis with the Statistical Analysis System. Initially, the NLIN procedure was
      applied to fit an exponential model of the form y = alpha + beta*[1 - exp (
      Gamma*dose)] + e. Thereafter, meta-analysis was conducted by means of nonlinear
      mixed models, which were fitted by a full maximum likelihood method as
      implemented in the NLMIXED procedure. The nonlinear model used for the analysis
      allowed for separate plateaus or different efficiencies of the methionine
      sources. Mixed modeling was applied to account for heterogeneity among the
      studies in all regression parameters for both sources of methionine via random
      effects. Statistical hypotheses were tested by the asymptotic Wald test. In
      addition, potential co-variables were tested for inclusion as linear regressors
      for the nonlinear model parameters. In conclusion, the null hypothesis of equal
      plateaus of the 2 methionine sources was not rejected. The analyses of the
      response variables average daily gain (ADG) and gain to feed ratio (GF) showed a
      highly significant difference between the tested methionine sources. The
      covariate age at start of experiment significantly affected the intercept term
      alpha for the response variables ADG and GF, respectively. The meta-analysis
      showed that biological efficiencies of DL-methionine-hydroxy-analogue-free-acid
      were 81 and 79% of the values for DL-methionine, on an equimolar basis, for ADG
      and GF, respectively.

PMID- 18809866
TI  - Restricting the intake of a cereal-based feed in free-range-pastured poultry:
      effects on performance and meat quality.
AB  - Pastures are assumed to be good sources of alpha-linolenic acid (ALA) and other
      bioactive compounds. In this study, we evaluated the effects of restricting the
      intake of a cereal-based feed on the consumption of a legume-based pasture, and
      consequently on poultry performance and meat quality. Broilers of the RedBro Cou
      Nu x RedBro M genotype were fed a cereal-based feed at different intake
      restriction levels (100, 75, or 50% of ad libitum intake) in portable floorless
      pens located on a subterranean clover (Trifolium subterraneum) pasture. Control
      birds were maintained at the same site in identical pens but had no access to
      pasture. The results revealed that, although the growth rate achieved was below
      the levels expected for the genotype, restriction of cereal-based feed intake had
      a significant impact on broiler weight gain and feed conversion while leading to
      an increase in relative leguminous pasture intake (from 1.6 to 4.9% of the total
      intake, on a DM basis). In addition, bird performance was positively influenced
      by pasture consumption. The capacity of ingested pasture to modulate carcass
      characteristics, broiler meat fatty acid profiles, and the meat content of total
      cholesterol, tocopherols, and to-cotrienols was investigated in broiler chickens
      slaughtered on d 64. Pasture intake decreased carcass yield (P < 0.05) and meat
      pH (P < 0.001) and improved breast skin pigmentation (P < 0.001). Consumption of
      the leguminous pasture had a marginal effect in the vitamin E profiles and
      cholesterol contents of broiler meat (P < 0.05), although it significantly
      affected the meat fatty acid profile. Although pasture intake did not influence
      the linoleic acid content of poultry meat, the levels of n-3 polyunsaturated
      fatty acids in breast meat [ALA (P < 0.001), eicosapentaenoic acid (P < 0.001),
      docosapentaenoic acid (P < 0.001), and docosahexaenoic acid (P < 0.001)] were
      significantly greater in birds consuming the leguminous biomass. Overall, the
      data suggest an important deposition of ALA and some conversion of ALA to its
      derivatives in pastured broilers subjected to a restriction of cereal-based feed.

PMID- 18809867
TI  - Productive performance and egg quality of brown egg-laying hens in the late phase
      of production as influenced by level and source of calcium in the diet.
AB  - A total of 1,152 Lohmann Brown laying hens were used to study the influence of
      level (3.5 and 4.0%) and source (coded FIN, COA, and OYS) of Ca in the diet on
      productive performance and egg quality from 58 to 73 wk of age. The FIN diet
      contained all the Ca carbonate as fine limestone (LIM). In the COA and OYS diets,
      40% of the fine LIM was substituted with either coarse LIM or oyster shell. Each
      treatment was replicated 8 times (24 hens). Productive performance and egg
      quality traits were recorded every 4 wk, and tibia characteristics and shell
      quality traits were determined at 73 wk of age. An increase in Ca intake from
      4.08 to 4.64 g/hen per day improved egg production (71.2 vs. 74.9%; P < 0.001),
      egg mass (49.0 vs. 51.4 g; P < 0.05), and feed conversion ratio (2.43 vs. 2.30 kg
      of feed/kg of egg; P < 0.001). In addition, an increase in Ca intake improved
      shell weight (9.98 vs. 10.20%; P < 0.05), shell thickness (0.342 vs. 0.351 mm; P
      < 0.01), and shell density (82.0 vs. 83.8 mg/cm2; P < 0.001). Calcium source had
      no effect on productive performance, tibia characteristics, or egg quality except
      for shell density, which was greater for hens fed COA than for hens fed FIN, with
      hens fed OYS being intermediate (81.9 vs. 84.0 vs. 82.7 mg/cm2, respectively; P <
      0.05). It was concluded that Brown egg-laying hens in the late phase of
      production require more than 3.5% Ca in the diet (4.08 g of Ca/hen per day) and
      that the substitution of 40% of fine LIM with COA or OYS does not affect
      productive performance and has little impact on shell quality and tibia
      characteristics.

PMID- 18809868
TI  - Factors affecting intestinal health in poultry.
AB  - The gastrointestinal (GI) tract has the most extensive exposed surface in the
      body and is constantly exposed to a wide variety of potentially harmful
      substances. The GI tract acts as a selective barrier between the tissues of the
      bird and its luminal environment. This barrier is composed of physical, chemical,
      immunological, and microbiological components. A wide range of factors associated
      with diet and infectious disease agents can negatively affect the delicate
      balance among the components of the chicken gut and, as a result, affect health
      status and production performance of birds in commercial poultry operations.
      Phasing out of antibiotic growth promoters from poultry diets in Europe and
      recent moves toward reduction or removal of these compounds in other parts of the
      world including North America will likely change the microbial profile of the GI
      tract environment in commercial poultry. This paper reviews the GI tract from
      developmental, immunological, and microbial standpoints and then discusses
      factors that can affect health status of this system. Necrotic enteritis and
      coccidiosis and their interactions, and possible consequences of antibiotic
      growth promoter removal from poultry diets with respect to these diseases, are
      discussed in more detail.

PMID- 18809869
TI  - Absence of donor-derived zona pellucida protein C homolog in the inner
      perivitelline layer of Peking duck (Anas platyrhynchos)-Japanese quail (Coturnix
      coturnix japonica) chimeras (Duails).
AB  - Avian blastodermal cells at stage X are used to produce interspecies chimeras for
      heterogenous poultry reproduction. However, recipient-derived inner perivitelline
      layer (IPVL)-enclosed donor-derived ova may affect the efficiency of germline
      transmission via chimera. Among the proteins in the IPVL, zona pellucida protein
      C (ZPC) plays an important role in sperm-egg binding and inducing the acrosome
      reaction. In the present study, Peking duck blastodermal cells at stage X were
      transferred into subgerminal cavities of Japanese quail embryos at the same
      stage. Fourteen female duck-quail chimeras (duails) were hatched and raised to
      sexual maturity. After being screened by PCR, 3 duails were selected for
      examination of donor-derived ZPC. A total of 152 IPVL protein samples from the
      individual eggs laid by the 3 duails then underwent a preliminary examination for
      the presence of donor-derived ZPC by means of SDS-PAGE, periodic acid-Schiff
      staining, and Western blotting. A novel 35-kDa ZPC, not observed in quail but in
      duck, was found in the IPVL of the duails. Further analysis of peptide mass
      fingerprinting of Peking duck ZPC, Japanese quail ZPC, and the 35-kDa duail ZPC
      by matrix-assisted laser desorption-ionization reflectron time-of-flight mass
      spectrometry revealed that the novel ZPC was an isoform of quail ZPC. Moreover,
      comparison of N-terminal amino acid sequences of these 3 ZPC confirmed that the
      35-kDa quail ZPC had more amino acids at the N terminus than did native quail
      ZPC, and none of the donor-derived ZPC was found in the duails. These findings
      suggest that it would be difficult to obtain donor-derived offspring by natural
      mating of interspecies chimeras.

PMID- 18809870
TI  - Polymorphisms in uncoupling protein, melanocortin 3 receptor, melanocortin 4
      receptor, and pro-opiomelanocortin genes and association with production traits
      in a commercial broiler line.
AB  - Because avian uncoupling protein (avUCP), melanocortin 3 receptor (MC3R),
      melanocortin 4 receptor (MC4R), and pro-opiomelanocortin (POMC) genes may be
      associated with production traits [e.g., BW, weight gain (WG), and feed
      conversion ratio (FCR)], male and female broilers from an elite broiler line were
      screened for polymorphisms in these genes. The PCR-restriction fragment length
      polymorphism (RFLP) tests were developed to type the missense polymorphisms
      UCPAla118Val, MC4RSer76Leu, MC3R-Met54Leu, and Gly104Ser and POMCPro61Leu. Of 39
      single nucleotide polymorphisms identified in all 4 genes, 24/39 were transitions
      with 11 having a C to T change. Of the 23 polymorphisms in UCP, 17 represented at
      least 7 haplotypes in this pedigreed broiler line. The UCP Ala-118Val allele was
      associated with a) high feed efficiency (FE; P = 0.03) and WG (P = 0.053) in
      selected males, and b) high BW in selected females (P = 0.07) and unselected
      males (P = 0.015). The UCPVal118Val allele was found in approximately 10% of the
      birds that were screened. Five silent substitutions, 3 in MC3R and 2 in MC4R,
      were also identified. Thirteen polymorphisms were identified in the POMC gene
      representing at least 3 different alleles. A missense Pro61Leu heterozygote was
      associated with greater BW in females. The heterozygote MC3R Gly104Ser
      polymorphism was associated with greater FE in selected males (P = 0.03) and
      greater BW in unselected males (P = 0.007). The MC4R Ser76Leu heterozygote
      polymorphism was associated with greater BW than the Leu76 homozygote in females
      (P = 0.05). From these findings, we hypothesize that UCP, MC3R, MC4R and POMC
      genes may play important roles and could be candidate loci for production traits
      such as feed conversion and BW in commercial broiler breeding stock.

PMID- 18809871
TI  - Expression of genes involved in the somatotropic, thyrotropic, and corticotropic
      axes during development of Langshan and Arbor Acres chickens.
AB  - We investigated changes in mRNA expression of the somatotropic, thyrotropic, and
      corticotropic axes of Langshan (LS) and Arbor Acres (AA) broiler chickens during
      embryonic and postnatal development. We found an inverse expression profile
      between pituitary growth hormone (GH) and hepatic GH receptor mRNA [postnatal d
      (P)28 to P42], insulin-like growth factor (IGF)-I, and IGF-IR (P0 to P42),
      respectively. Hepatic IGF-I was a major point of control in the GH-IGF axis from
      P0 to P28. Pituitary GH-releasing hormone receptor may serve an autocrine
      paracrine function from P0 to P28, and hypothalamic ghrelin may affect growth by
      stimulating the release of hepatic IGF-I from embryonic d (E)8 to P28.
      Hypothalamic ghrelin might interact with corticotropin-releasing hormone (CRH)
      from P0 to P28. Hepatic IGF-binding protein-2 regulated growth by regulating
      hepatic IGF-II bioavailability from P0 to P42. Hepatic IGF-binding protein-5 was
      an important IGF mediator. A coexpression profile was found between hypothalamic
      GH-releasing hormone (E10 to E16 and P0 to P42), somatostatin (SS; P0 to P28),
      thyrotropin-releasing hormone (E10 to E16 and P0 to P28), ghrelin (P0 to P42),
      and pituitary GH mRNA, hypothalamic SS (P0 to P28), corticotropin-releasing
      hormone (P0 to P42), thyrotropin-releasing hormone (E10 to E18 and P0-P42), and
      thyroid-stimulating hormone-beta mRNA, respectively. Moreover, AA chickens were
      fed a nutrient-rich AA diet (as a control group) and LS chickens were fed either
      a less nutritious LS diet or the AA diet. Langshan and AA chickens fed the same
      AA diet showed no differences in pituitary GH, hypothalamic SS, ghrelin, hepatic
      IGF-I, or GH receptor mRNA. Our data indicate that select genes may show parallel
      expression during certain periods of development, and that differences in BW and
      gene expression respond differently to nutrient intake in LS and AA chickens. Our
      findings may help improve the molecular breeding of chickens.

PMID- 18809872
TI  - Impact of feeding program after light stimulation through early lay on the
      reproductive performance of broiler breeder hens.
AB  - Skip-a-day feed restriction is a common industry management technique that is
      used in rearing broiler breeder pullets. Often pullets are maintained on a skip-a
      day feeding program after they have been photostimulated for reproduction, and in
      some cases until 5% egg production is reached. The current research examined
      whether providing daily nutrient intake during the critical period of ovarian
      development that follows photostimulation for reproduction improves subsequent
      egg production. Pullets and cockerels were fed on a skip-a-day basis during
      rearing. Pullets were weighed at 20 wk of age and then distributed into 30 laying
      pens such that each pen had a similar BW distribution. Each individual laying pen
      consisted of 35 hens and 4 roosters. At 21 wk of age, the birds were
      photostimulated for reproduction; 15 of the laying pens were placed on an every
      day feeding schedule, whereas the other 15 pens were maintained on a skip-a-day
      feeding schedule until they reached 8% egg production at 26.5 wk of age. From
      26.5 to 65 wk of age, all hens were fed on an every-day basis. The CV of BW did
      not differ between the hens of the 2 treatment groups at any point from 21 to 64
      wk of age. Weekly percentage hen-day egg production was greater (P < 0.05) in the
      hens fed on the every-day versus skip-a-day program after photostimulation from
      wk 25 of age to 65 wk of age except for wk 29, 30, 35, 37, 39, 46, and 47 of age.
      Total hen-day egg production through 65 wk of age in the hens that were provided
      feed every day after photostimulation was greater (172 vs. 155 eggs/hen) than in
      hens fed on a skip-a-day basis until 26.5 wk of age. These results suggest that
      continuing skip-a-day feeding after photostimulation until reaching 8% egg
      production does not improve BW uniformity, but does cause lasting reproductive
      dysfunction in broiler breeder hens.

PMID- 18809873
TI  - Mesotocin increases the sensitivity of the hen oviduct uterus to arginine
      vasotocin.
AB  - The present study was performed to elucidate whether mesotocin (MT), one of avian
      neurohypophysial hormones, relates to the action of arginine vasotocin (AVT) on
      oviposition of hens. The ratio of AVT-induced oviposition was increased when 1
      microg/hen of MT was injected together with AVT. An intravenous injection of 1
      microg/hen of MT caused an increase in the binding affinity of the uterine AVT
      receptor and a decrease in the binding capacity. Blood MT concentrations measured
      by RIA increased approximately 1 min before oviposition during the period of the
      bearing-down behavior, but the AVT concentration did not change at this time. The
      blood AVT concentration dramatically increased within 1 min just after
      oviposition. The results suggest that MT may have an effect of enhancing the
      inducing oviposition by AVT through the increase in the sensitivity of the uterus
      to AVT at oviposition in hens.

PMID- 18809874
TI  - Influences of hypoxia on hatching performance in chickens with different genetic
      adaptation to high altitude.
AB  - The experiments were conducted to assess how hatching performance is affected by
      chicken breeds and environment of high altitude and to analyze the vital factor
      of the low hatchability at a 2,900-m altitude. Eggs of Tibetan and Dwarf chickens
      were incubated at conditions of normobaric normoxia, normobaric hypoxia,
      hypobaric hypoxia, and supplemental O2 at high altitude (hypobaric normoxia)
      during the whole incubation or at 0 to 7, 8 to 14, and 15 to 22 d of incubation,
      respectively. The results showed that the Tibetan chickens had greater
      hatchability (79.72%), lower water loss (12.90%), greater relative embryo weight
      (38.08%), and relative chick weight (68.41%) compared with the Dwarf chickens
      (31.69, 15.79, 30.71, and 65.21%, respectively) when both of them were incubated
      at a 2,900-m altitude. The hatchability was 71.60% in Tibetan chicken and 36.23%
      in Dwarf chicken under the normobaric hypoxia condition. The hatchability of
      chicken was efficiently increased with supplemental O2. The previous results
      indicated that the O2 deficit is the main factor resulting in the low
      hatchability and the poor chick quality of the lowland chicken breed when
      incubated at a 2,900-m altitude. Breeding chickens for adaptability to hypoxia
      and supplemental O2 is a good way to improve the hatchability and chick quality
      at that altitude.

PMID- 18809875
TI  - Physical-mechanical modifications of eggs for food-processing during storage.
AB  - Physical-mechanical properties of egg constituents and their modifications during
      storage and poststorage greatly influence the efficiency of food processing, such
      as the separation of white and yolk by mechanical shelling. Thick albumen height,
      Haugh unit, yolk index and vitelline membrane-yolk system strength of eggs from
      Hy-Line White and Lohmann Brown hens were analyzed during 7 mo of storage at 0
      degrees C performing 3 poststorage treatments: i) immediately after
      refrigeration, T1; ii) after a further 6 h at 18 degrees C after refrigeration,
      T2; and iii) after a week at 18 degrees C after refrigeration, T3. For all
      qualitative parameters considered, this last poststorage treatment appeared to be
      the factor that produced the highest decrements; with respect to the first
      poststorage treatment, a further week at 18 degrees C after refrigeration can
      involve mean decreases of about 19, 14, 14, and 16% in thick albumen height,
      Haugh unit, yolk index, and vitelline membrane-yolk system strength (in terms of
      maximum force), respectively. During about 7 mo of storage at 0 degrees C, the
      latter parameter decreases, on average, by 10%. Increasing the storage time,
      physical-mechanical behavior was sometimes divergent from the observed trends.

PMID- 18809876
TI  - Role of calpains in postmortem proteolysis in chicken muscle.
AB  - Tenderness is governed by postmortem biochemical processes, particularly
      proteolysis. In mammals, the calpain system is generally accepted as the main
      system involved in postmortem proteolysis. In poultry, the 2 calpains (mu and
      mu/m--a form only found in bird tissue) have greater calcium sensitivity. In this
      study, we quantified by zymography the changes in postmortem calpain system
      activity. The mu/m-calpain activity remained steady, whereas the mu-calpain
      activity had disappeared by 6 h after postmortem, showing an activation by
      calcium. Changes in the electrophoretic pattern of sarcoplasmic and myofibrillar
      proteins are observed in the first postmortem hours concomitantly to the decrease
      in mu-calpain activity. The 30-kDa protein, considered as a good marker of
      postmortem aging in cattle, appeared from 6 h and then steadily increased. In
      chicken muscle, the rapid maximum tenderness reached could be explained by a
      greater activation of the calpain system.

PMID- 18809877
TI  - Effects of high temperature on multiple parameters of broilers in vitro and in
      vivo.
AB  - The effects of high temperature on multiple parameters of broilers were evaluated
      both in vitro and in vivo. In the in vitro study, the bilateral musculus
      fibularis longus muscles of 8 broilers were isolated and incubated at either 41.5
      or 44.5 degrees C. The greater incubation temperature increased mitochondrial
      H2O2 production by 28.0% (P < 0.0001), malondialdehyde concentration by 16.8% (P
      = 0.0368), and lactate concentration by 33.0% (P < 0.0001) and decreased
      mitochondrial Ca2+-ATPase activity by 19.6% (P = 0.0001). In the in vivo study,
      180 four-week-old broilers were kept in 3 controlled-environment chambers for 3
      wk. High temperature increased mitochondrial H2O2 production (P < 0.05) in liver,
      malondialdehyde concentration in liver and breast muscle, and lactate
      concentration in breast muscle (P < 0.05). In addition, it inhibited
      mitochondrial Ca2+-ATPase activity in muscle and liver (P < 0.05). High
      temperature also significantly decreased initial pH and increased L*, drip loss,
      and shear force of broiler breast muscle.

PMID- 18809878
TI  - Effects of irradiation on survival and growth of Listeria monocytogenes and
      natural microflora in vacuum-packaged turkey hams and breast rolls.
AB  - The effect of electron beam irradiation on the survival and growth of Listeria
      monocytogenes and natural microflora in oven-roasted turkey breast rolls and
      turkey hams was evaluated. Slices of turkey breast rolls and hams were inoculated
      with a 5-strain mixture of L. monocytogenes to achieve 10(6) to 10(7) cfu/cm2;
      vacuum-packaged; irradiated at 0 (control), 1.0, 1.5, 2.0, or 2.5 kGy; and stored
      at 4 degrees C for up to 28 d. Numbers of naturally occurring bacteria on sliced
      turkey hams and breast rolls were 2.72 and 6.22 log10 cfu/cm2, respectively. The
      values of the radiation dose that results in 90% reduction of viable L.
      monocytogenes in breast rolls and hams were 0.52 and 0.47 kGy, respectively. For
      breast rolls, the log10 reductions of L. monocytogenes after irradiation at 1.0
      and 2.5 kGy were 1.5 and 4.7, respectively, whereas they were 2.0 and 5.5 for
      hams. The log10 reductions of aerobic plate count (APC) in breast rolls after 1.0
      and 2.0 kGy of irradiation were 2.9 and 5.2, whereas that of hams was < 10
      cfu/cm2 after 1.0 and 2.0 kGy of irradiation. In 2.0-kGy irradiated hams, L.
      monocytogenes grew to 4.82 log10 cfu/cm2 after 28 d of storage at 4 degrees C,
      whereas APC increased to 2.98 log10 cfu/cm2, respectively. In breast rolls after
      14 d of storage, APC in 1.0-kGy irradiated samples increased to 7.53 log10
      cfu/cm2, and APC increased to 2.63 and 4.68 log10 cfu/cm2 for 2.0-kGy irradiated
      breast rolls after 14 and 28 d of storage. However, during the storage of breast
      rolls, L. monocytogenes grew slowly or even stopped to grow in both nonirradiated
      and irradiated breast rolls due to the competitive inhibition of natural flora in
      breast rolls. This study showed that irradiation (1.0 to 2.5 kGy) effectively
      reduced the number of L. monocytogenes and natural flora. However, L.
      monocytogenes and natural flora that survived irradiation could multiply during
      the 28-d storage period at 4 degrees C. Thus, additional hurdles are needed to
      ensure the microbial safety after low-dose irradiation.

PMID- 18809879
TI  - Influence of hen age and molting treatments on shell egg exterior, interior, and
      contents microflora and Salmonella prevalence during a second production cycle.
AB  - The objective of this study was to determine if increasing hen age and 3
      different molting treatments influenced the total microflora counts or the
      prevalence of Salmonella spp. on the exterior of the egg shell, within the
      interior shell, or in the contents. Eggs from Hy-Line W-98 and Bovans White layer
      strains were sampled approximately every 28 d from 70 to 114 wk of age, with the
      molting period from 66 to 70 wk of age. Layers were utilized from the 35th North
      Carolina Layer Performance and Management Test and managed under identical
      husbandry practices. This study consisted of nonfasted, nonmolted, and feed
      restricted treatments with the use of 135 eggs per layer strain, for a total of
      270 eggs sampled per period. The exterior, interior shell, and contents were
      spiral plated onto plate count agar to calculate the total aerobic counts.
      Additional preenrichment, enrichment, conformational, and biochemical procedures
      were performed to test for the presence of Salmonella spp. Hen age and molting
      treatment significantly (P < 0.05) affected the microbial loads on all 3 egg
      components. Exterior, interior, yolk, and albumen counts increased during the
      molt period to as much as 1 log unit higher than the highest countable plate,
      which was 10(5). Exterior, interior, and contents counts significantly increased
      (P < 0.05) during period 15, with a significant increase (P < 0.05) in the
      interior also in period 14, and in the contents in periods 14 and 17. There were
      a total of 360 egg pools, and of those, 4 were positive Salmonella samples. Both
      the interior and exterior shell components and 2 of the 3 molting treatments had
      positive samples. Of these positives, 4 were confirmed as Salmonella Braenderup.
      Three positives were associated with the interior component, whereas 1 positive
      was associated with the exterior shell component. Three of the 4 samples were
      related to the nonfasted treatment, whereas the remaining positive was found in
      the non-molted treatment.

PMID- 18809880
TI  - Genotypic and phenotypic diversity within three Campylobacter populations
      isolated from broiler ceca and carcasses.
AB  - The main aim of this study was to trace Campylobacter subtypes colonizing Italian
      broilers and carcasses in and between flocks. Overall, 209 Campylobacter isolates
      were collected from ceca (n = 94) and carcasses (n = 115) of broilers belonging
      to 3 different flocks reared in the same farm during subsequent rotations and
      processed in the same slaughterhouse. All isolates were identified by multiplex
      polymerase chain reaction and genotyped by amplified fragment length
      polymorphism. Furthermore, 166 out of 209 strains were phenotyped by
      antimicrobial resistance profile (R-type). The results of genetic and phenotypic
      characterization showed that (1) multiple Campylobacter species and subtypes can
      colonize the same broiler and carcass; (2) common Campylobacter subtypes in ceca
      and carcasses seem to be rare; and (3) carryover of Campylobacter subtypes
      between broiler flocks in the same house rarely occurs. The outcomes of this
      study should be taken into account for setting of isolate collection during
      epidemiological investigations to check sources and transmission routs of
      Campylobacter in broilers and poultry products.

PMID- 18809881
TI  - Head-to-cloaca electrical stunning of broilers.
AB  - This study was performed to identify the electrical current and exposure duration
      that would instantaneously render broiler chickens unconscious at slaughter when
      using a head-to-cloaca water bath stunner. The water in which the head was
      immersed was one electrode, and a steel-coned or cutaneous U-shaped electrode
      penetrating the cloaca was the other electrode. When an electrode penetrating the
      cloaca was used, a 640-Hz sinusoidal current induced a tonic-clonic phase on the
      electroencephalogram that lasted for 10 +/- 3 s and an exhaustion phase that
      lasted for 34 +/- 12 s. The heart rate was 375 +/- 39 beats/min before stunning.
      After stunning, the electrocardiogram revealed fibrillating for 429 +/- 58 s,
      after which the heart activity stopped. When a U-shaped electrode was placed on
      the skin at the cloaca, the same phenomenon was induced. A general epileptiform
      insult was induced when using a pulsed alternating square wave current of 33 mA
      (peak 60 V, 600 Hz, and a duty cycle of 50%), which lasted, on average, for 25 s
      (n = 25). When the broilers were bled within 14 s after stunning, they remained
      unconscious and the heart activity stopped after 237 +/- 103 s. We concluded from
      this experiment that broilers were effectively stunned with an average current of
      111 mA (50 V, 640 Hz, sinusoidal alternating current) for 1 s when using a water
      bath in which the head of the broiler was immersed in water, with the water being
      one electrode and a steel electrode penetrating the cloaca or placed around it
      being the other electrode. Energy use could be reduced when an alternating pulsed
      square wave is used when the broilers are stunned, by using a current of
      approximately 33 mA (peak of 60 V, frequency of 600 Hz, and a 50% duty cycle).

PMID- 18809882
TI  - Campylobacter prevalence in the broiler supply chain in the Netherlands.
AB  - After a national control program, data on Campylobacter prevalence in the broiler
      supply chain in the Netherlands were gathered for 3 sampling points: departure of
      broiler farm and arrival and departure of the slaughterhouse. Monitoring data
      from this control program for 2002 to 2005 were analyzed to find correlations and
      possible trends in the data. As expected, the greatest correlations were found
      between adjacent sampling points. A high correlation was expected between number
      of animals slaughtered and Campylobacter prevalence, because it is assumed that
      larger companies will have greater hygiene standards due to better implication of
      food safety regulations. However, statistical analysis showed that there was no
      clear correlation between company size and Campylobacter prevalence. Data
      analysis further identified an increasing trend in Campylobacter prevalence at
      departure of slaughterhouse from 2002 to 2005 with strong seasonality at all 3
      sampling points. Measures to control Campylobacter, therefore, need to be
      reconsidered and possibly intensified to achieve a reduction in Campylobacter
      positives.

PMID- 18809884
TI  - Understanding and improving on 1 problem per visit.

PMID- 18809885
TI  - Statins and postoperative delirium.

PMID- 18809886
TI  - Unravelling the contributions of social, environmental and genetic factors to
      health differences.

PMID- 18809887
TI  - Disparities in the care of chest pain.

PMID- 18809888
TI  - Clinical trials regulation--how Canada compares.

PMID- 18809889
TI  - Moratorium urged for foreign visa trainees.

PMID- 18809890
TI  - National organ allocation mechanism to be sought.

PMID- 18809892
TI  - Europeans claim industry handouts are not a problem.

PMID- 18809893
TI  - Complaints rise but legal actions decline.

PMID- 18809894
TI  - Medicine and sorcery in the Republic of Congo.

PMID- 18809895
TI  - Delirium after elective surgery among elderly patients taking statins.
AB  - BACKGROUND: Postoperative delirium after elective surgery is frequent and
      potentially serious. We sought to determine whether the use of statin medications
      was associated with a higher risk of postoperative delirium than other
      medications that do not alter microvascular autoregulation. METHODS: We conducted
      a retrospective cohort analysis of 284 158 consecutive patients in Ontario aged
      65 years and older who were admitted for elective surgery. We identified exposure
      to statins from outpatient pharmacy records before admission. We identified
      delirium by examining hospital records after surgery. RESULTS: About 7% (n = 19
      501) of the patients were taking statins. Overall, 3195 patients experienced
      postoperative delirium; the rate was significantly higher among patients taking
      statins (14 per 1000) than among those not taking statins (11 per 1000) (odds
      ratio [OR] 1.30, 95% confidence interval [CI] 1.15-1.47, p < 0.001). The
      increased risk of postoperative delirium persisted after we adjusted for multiple
      demographic, medical and surgical factors (OR 1.28, 95% CI 1.12-1.46) and
      exceeded the increased risk of delirium associated with prolonging surgery by 30
      minutes (OR 1.20, 95% CI 1.19-1.21). The relative risk associated with statin use
      was somewhat higher among patients who had noncardiac surgery than among those
      who had cardiac surgery (adjusted OR 1.33, 95% CI 1.16-1.53), and extended to
      more complicated cases of delirium. We did not observe an increased risk of
      delirium with 20 other cardiac or noncardiac medications. INTERPRETATION: The use
      of statins is associated with an increased risk of postoperative delirium among
      elderly patients undergoing elective surgery.

PMID- 18809896
TI  - A population-based analysis of the health experience of African Nova Scotians.
AB  - BACKGROUND: People of African descent living in Britain and the United States
      have higher rates of morbidity from chronic disease than among the general
      population. We investigated whether the same applied to people of African descent
      living in a Canadian province. METHODS: We used administrative data to calculate
      10-year cumulative incidence rate ratios for the period 1996-2005 for treated
      circulatory disease, diabetes mellitus and psychiatric disorders in Preston
      (population 2425), a community of predominantly African Nova Scotians. We used
      data for the province of Nova Scotia as a whole as the population reference
      standard. We also calculated 10-year incidence rate ratios for visits to family
      physicians and specialists and for admissions to hospital. We compared these
      findings with those in 7 predominantly white communities in Nova Scotia with
      otherwise similar socio-economic characteristics. RESULTS: In the province as a
      whole, we identified 787,787 incident cases for the 3 disease groups over the 10
      year period. Incidence rate ratios for the community of interest relative to the
      provincial population were significantly elevated for the 3 diseases: circulatory
      disease (1.19, 95% CI 1.08-1.29), diabetes (1.43, 95% CI 1.21-1.64) and
      psychiatric disorders (1.13, 95% CI 1.06-1.20). Incidence rate ratios in the
      community of interest were also higher than those in the comparison communities.
      Visits to family physicians and specialists for circulatory disease and diabetes
      were similarly elevated, but the pattern was less clear for visits for
      psychiatric disorders and hospital admissions. INTERPRETATION: African Nova
      Scotians had higher morbidity levels associated with treated disease, which could
      not be explained by socio-economic characteristics, recent immigration or
      language. Apart from psychiatric disorders, use of specialist services was
      consistent with morbidity. Further study is needed to investigate the relative
      contribution of genetic, biological, behavioural, psychosocial and environmental
      factors.

PMID- 18809897
TI  - Presentation of stable angina pectoris among women and South Asian people.
AB  - BACKGROUND: There is speculation that women and South Asian people are more
      likely than men and white people to report atypical angina and that they are less
      likely to undergo invasive management of angina. We sought to determine whether
      atypical symptoms of angina pectoris in women and South Asians impacted
      clinically important outcomes and clinical management. METHODS: We prospectively
      identified 2189 South Asian people and 5605 white people with recent-onset chest
      pain at 6 chest-pain clinics in the United Kingdom. We documented hospital
      admissions for acute coronary syndromes, coronary deaths as well as coronary
      angiography and revascularization procedures. RESULTS: Atypical chest pain was
      reported by more women than men (56.5% vs 54.5%, p < 0.054) and by more South
      Asian patients than white patients (59.9% vs 52.5%, p < 0.001). Typical symptoms
      were associated with coronary death or acute coronary syndromes among women
      (hazard ratio [HR] 2.30, 95% CI 1.70-3.11, p < 0.001) but not among men (HR 1.23,
      95% CI 0.96-1.57, p = 0.10). Typical symptoms were associated with coronary
      outcomes in both South Asian and white patients. Among those with typical
      symptoms, women (HR 0.76, 95% CI 0.63-0.92, p = 0.004) and South Asian patients
      (HR 0.52, 95% CI 0.41-0.67, p < 0.001) were less likely than men and white
      patients to receive angiography. INTERPRETATION: Compared to those with atypical
      chest pain, women and South Asian patients with typical pain had worse clinical
      outcomes. However, sex and ethnic background did not explain differences in the
      use of invasive procedures.

PMID- 18809898
TI  - Exaggeration of treatment benefits using the "event-based" number needed to
      treat.

PMID- 18809899
TI  - What is your call?: cobblestone-like skin. Elephantiasis nostras verrucosa.

PMID- 18809900
TI  - TASER safety.

PMID- 18809901
TI  - Methamphetamine strategy requires evaluation.

PMID- 18809905
TI  - Granulocytic sarcoma of the skin.

PMID- 18809906
TI  - Physician advocacy essential for Canada's First Nations.

PMID- 18809907
TI  - Loss of p120 catenin and links to mitotic alterations, inflammation, and skin
      cancer.
AB  - Tumor formation involves epigenetic modifications and microenvironmental changes
      as well as cumulative genetic alterations encompassing somatic mutations, loss of
      heterozygosity, and aneuploidy. Here, we show that conditional targeting of p120
      catenin in mice leads to progressive development of skin neoplasias associated
      with intrinsic NF-kappaB activation. We find that, similarly, squamous cell
      carcinomas in humans display altered p120 and activated NF-kappaB. We show that
      epidermal hyperproliferation arising from p120 loss can be abrogated by IkappaB
      kinase 2 inhibitors. Although this underscores the importance of this pathway,
      the role of NF-kappaB in hyperproliferation appears rooted in its impact on
      epidermal microenvironment because as p120-null keratinocytes display a growth
      arrested phenotype in culture. We trace this to a mitotic defect, resulting in
      unstable, binucleated cells in vitro and in vivo. We show that the abnormal
      mitoses can be ameliorated by inhibiting RhoA, the activity of which is
      abnormally high. Conversely, we can elicit such mitotic defects in control
      keratinocytes by elevating RhoA activity. The ability of p120 deficiency to
      elicit mitotic alterations and chronic inflammatory responses, that together may
      facilitate the development of genetic instability in vivo, provides insights into
      why it figures so prominently in skin cancer progression.

PMID- 18809908
TI  - New insights into cadherin function in epidermal sheet formation and maintenance
      of tissue integrity.
AB  - Co-expression and gene linkage have hampered elucidating the physiological
      relevance of cadherins in mammalian tissues. Here, we combine conditional gene
      ablation and transgenic RNA interference to uncover new roles for E- and P
      cadherins in epidermal sheet formation in vitro and maintenance of epidermal
      integrity in vivo. By devising skin-specific RNAi technology, we demonstrate that
      cadherin inhibition in vivo impairs junction formation and intercellular adhesion
      and increases apoptosis. These defects compromise epidermal barrier function and
      tissue integrity. In vitro, with only E-cadherin missing, epidermal sheet
      formation is delayed, but when both cadherins are suppressed, defects extend to
      adherens junctions, desmosomes, tight junctions and cortical actin dynamics.
      Using different rescue strategies, we show that cadherin level rather than
      subtype is critical. Finally, by comparing conditional loss-of-function studies
      of epidermal catenins and cadherins, we dissect cadherin-dependent and
      independent roles of adherens junction components in tissue physiology.

PMID- 18809909
TI  - Melting of ice under pressure.
AB  - The melting of ice under pressure is investigated with a series of first
      principles molecular dynamics simulations. In particular, a two-phase approach is
      used to determine the melting temperature of the ice-VII phase in the range of 10
      50 GPa. Our computed melting temperatures are consistent with existing diamond
      anvil cell experiments. We find that for pressures between 10 and 40 GPa, ice
      melts as a molecular solid. For pressures above approximately 45 Gpa, there is a
      sharp increase in the slope of the melting curve because of the presence of
      molecular dissociation and proton diffusion in the solid before melting. The
      onset of significant proton diffusion in ice-VII as a function of increasing
      temperature is found to be gradual and bears many similarities to that of a type
      II superionic solid.

PMID- 18809910
TI  - Equatorial convergence of India and early Cenozoic climate trends.
AB  - India's northward flight and collision with Asia was a major driver of global
      tectonics in the Cenozoic and, we argue, of atmospheric CO(2) concentration
      (pCO(2)) and thus global climate. Subduction of Tethyan oceanic crust with a
      carpet of carbonate-rich pelagic sediments deposited during transit beneath the
      high-productivity equatorial belt resulted in a component flux of CO(2) delivery
      to the atmosphere capable to maintain high pCO(2) levels and warm climate
      conditions until the decarbonation factory shut down with the collision of
      Greater India with Asia at the Early Eocene climatic optimum at approximately 50
      Ma. At about this time, the India continent and the highly weatherable Deccan
      Traps drifted into the equatorial humid belt where uptake of CO(2) by efficient
      silicate weathering further perturbed the delicate equilibrium between CO(2)
      input to and removal from the atmosphere toward progressively lower pCO(2)
      levels, thus marking the onset of a cooling trend over the Middle and Late Eocene
      that some suggest triggered the rapid expansion of Antarctic ice sheets at around
      the Eocene-Oligocene boundary.

PMID- 18809911
TI  - Discovery of posttranslational maturation by self-subunit swapping.
AB  - Several general mechanisms of metallocenter biosynthesis have been reported and
      reviewed, and in all cases, the components or subunits of an apoprotein remain in
      the final holoprotein. Here, we first discovered that one subunit of an apoenzyme
      did not remain in the functional holoenzyme. The cobalt-containing low-molecular
      mass nitrile hydratase (L-NHase) of Rhodococcus rhodochrous J1 consists of beta-
      and alpha-subunits encoded by the nhlBA genes, respectively. An ORF, nhlE, just
      downstream of nhlBA, was found to be necessary for L-NHase activation. In
      contrast to the cobalt-containing L-NHase (holo-L-NHase containing Cys-SO(2)(-)
      and Cys-SO(-) metal ligands) derived from nhlBAE, the gene products derived from
      nhlBA were cobalt-free L-NHase (apo-L-NHase lacking oxidized cysteine residues).
      We discovered an L-NHase maturation mediator, NhlAE, consisting of NhlE and the
      cobalt- and oxidized cysteine-containing alpha-subunit of L-NHase. The
      incorporation of cobalt into L-NHase was shown to depend on the exchange of the
      nonmodified cobalt-free alpha-subunit of apo-L-NHase with the cobalt-containing
      cysteine-modified alpha-subunit of NhlAE. This is a posttranslational maturation
      process different from general mechanisms of metallocenter biosynthesis known so
      far: the unexpected behavior of a protein in a protein complex, which we named
      "self-subunit swapping."

PMID- 18809912
TI  - Adenosine receptor antagonists alter the stability of human epileptic GABAA
      receptors.
AB  - We examined how the endogenous anticonvulsant adenosine might influence gamma
      aminobutyric acid type A (GABA(A)) receptor stability and which adenosine
      receptors (ARs) were involved. Upon repetitive activation (GABA 500 microM),
      GABA(A) receptors, microtransplanted into Xenopus oocytes from neurosurgically
      resected epileptic human nervous tissues, exhibited an obvious GABA(A)-current
      (I(GABA)) run-down, which was consistently and significantly reduced by treatment
      with the nonselective adenosine receptor antagonist CGS15943 (100 nM) or with
      adenosine deaminase (ADA) (1 units/ml), that inactivates adenosine. It was also
      found that selective antagonists of A2B (MRS1706, 10 nM) or A3 (MRS1334, 30 nM)
      receptors reduced I(GABA) run-down, whereas treatment with the specific A1
      receptor antagonist DPCPX (10 nM) was ineffective. The selective A2A receptor
      antagonist SCH58261 (10 nM) reduced or potentiated I(GABA) run-down in
      approximately 40% and approximately 20% of tested oocytes, respectively. The ADA
      resistant, AR agonist 2-chloroadenosine (2-CA) (10 microM) potentiated I(GABA)
      run-down but only in approximately 20% of tested oocytes. CGS15943 administration
      again decreased I(GABA) run-down in patch-clamped neurons from either human or
      rat neocortex slices. I(GABA) run-down in pyramidal neurons was equivalent in A1
      receptor-deficient and wt neurons but much larger in neurons from A2A receptor
      deficient mice, indicating that, in mouse cortex, GABA(A)-receptor stability is
      tonically influenced by A2A but not by A1 receptors. I(GABA) run-down from wt
      mice was not affected by 2-CA, suggesting maximal ARs activity by endogenous
      adenosine. Our findings strongly suggest that cortical A2-A3 receptors alter the
      stability of GABA(A) receptors, which could offer therapeutic opportunities.

PMID- 18809913
TI  - Neanderthal exploitation of marine mammals in Gibraltar.
AB  - Two coastal sites in Gibraltar, Vanguard and Gorham's Caves, located at
      Governor's Beach on the eastern side of the Rock, are especially relevant to the
      study of Neanderthals. Vanguard Cave provides evidence of marine food supply
      (mollusks, seal, dolphin, and fish). Further evidence of marine mammal remains
      was also found in the occupation levels at Gorham's Cave associated with Upper
      Paleolithic and Mousterian technologies [Finlayson C, et al. (2006) Nature
      443:850-853]. The stratigraphic sequence of Gibraltar sites allows us to compare
      behaviors and subsistence strategies of Neanderthals during the Middle
      Paleolithic observed at Vanguard and Gorham's Cave sites. This evidence suggests
      that such use of marine resources was not a rare behavior and represents focused
      visits to the coast and estuaries.

PMID- 18809914
TI  - piRNA-mediated nuclear accumulation of retrotransposon transcripts in the
      Drosophila female germline.
AB  - Germline silencing of transposable elements is essential for the maintenance of
      genome integrity. Recent results indicate that this repression is largely
      achieved through a RNA silencing pathway that involves Piwi-interacting RNAs
      (piRNAs). However the repressive mechanisms are not well understood. To address
      this question, we used the possibility to disrupt the repression of the
      Drosophila I element retrotransposon by hybrid dysgenesis. We show here that the
      repression of the functional I elements that are located in euchromatin requires
      proteins of the piRNA pathway, and that the amount of ovarian I element piRNAs
      correlates with the strength of the repression in the female germline. Antisense
      RNAs, which are likely used to produce antisense piRNAs, are transcribed by
      heterochromatic defective I elements, but efficient production of these antisense
      small RNAs requires the presence in the genome of euchromatic functional I
      elements. Finally, we demonstrate that the piRNA-induced silencing of the
      functional I elements is at least partially posttranscriptional. In a repressive
      background, these elements are still transcribed, but some of their sense
      transcripts are kept in nurse cell nuclear foci together with those of the Doc
      retrotransposon. In the absence of I element piRNAs, either in dysgenic females
      or in mutants of the piRNA silencing pathway, sense I element transcripts are
      transported toward the oocyte where retrotransposition occurs. Our results
      indicate that piRNAs are involved in a posttranscriptional gene-silencing
      mechanism resulting in RNA nuclear accumulation.

PMID- 18809915
TI  - Regulation of floral organ abscission in Arabidopsis thaliana.
AB  - Abscission is a developmental program that results in the active shedding of
      infected or nonfunctional organs from a plant body. Here, we establish a
      signaling pathway that controls abscission in Arabidopsis thaliana from ligand,
      to receptors, to downstream effectors. Loss of function mutations in
      Inflorescence Deficient in Abscission (IDA), which encodes a predicted secreted
      small protein, the receptor-like protein kinases HAESA (HAE) and HAESA-like 2
      (HSL2), the Mitogen-Activated Protein Kinase Kinase 4 (MKK4) and MKK5, and a
      dominant-negative form of Mitogen-Activated Protein Kinase 6 (MPK6) in a mpk3
      mutant background all have abscission-defective phenotypes. Conversely,
      expression of constitutively active MKKs rescues the abscission-defective
      phenotype of hae hsl2 and ida plants. Additionally, in hae hsl2 and ida plants,
      MAP kinase activity is reduced in the receptacle, the part of the stem that holds
      the floral organs. Plants overexpressing IDA in a hae hsl2 background have
      abscission defects, indicating HAE and HSL2 are epistatic to IDA. Taken together,
      these results suggest that the sequential action of IDA, HAE and HSL2, and a MAP
      kinase cascade regulates the programmed separation of cells in the abscission
      zone.

PMID- 18809916
TI  - Sequence and genetic map of Meloidogyne hapla: A compact nematode genome for
      plant parasitism.
AB  - We have established Meloidogyne hapla as a tractable model plant-parasitic
      nematode amenable to forward and reverse genetics, and we present a complete
      genome sequence. At 54 Mbp, M. hapla represents not only the smallest nematode
      genome yet completed, but also the smallest metazoan, and defines a platform to
      elucidate mechanisms of parasitism by what is the largest uncontrolled group of
      plant pathogens worldwide. The M. hapla genome encodes significantly fewer genes
      than does the free-living nematode Caenorhabditis elegans (most notably through a
      reduction of odorant receptors and other gene families), yet it has acquired
      horizontally from other kingdoms numerous genes suspected to be involved in
      adaptations to parasitism. In some cases, amplification and tandem duplication
      have occurred with genes suspected of being acquired horizontally and involved in
      parasitism of plants. Although M. hapla and C. elegans diverged >500 million
      years ago, many developmental and biochemical pathways, including those for dauer
      formation and RNAi, are conserved. Although overall genome organization is not
      conserved, there are areas of microsynteny that may suggest a primary biological
      function in nematodes for those genes in these areas. This sequence and map
      represent a wealth of biological information on both the nature of nematode
      parasitism of plants and its evolution.

PMID- 18809917
TI  - CD4+ T cells support glial neuroprotection, slow disease progression, and modify
      glial morphology in an animal model of inherited ALS.
AB  - Neuroinflammation, marked by gliosis and infiltrating T cells, is a prominent
      pathological feature in diverse models of dominantly inherited neurodegenerative
      diseases. Recent evidence derived from transgenic mice ubiquitously
      overexpressing mutant Cu(2+)/Zn(2+) superoxide dismutase (mSOD1), a chronic
      neurodegenerative model of inherited amyotrophic lateral sclerosis (ALS),
      indicates that glia with either a lack of or reduction in mSOD1 expression
      enhance motoneuron protection and slow disease progression. However, the
      contribution of T cells that are present at sites of motoneuron injury in mSOD1
      transgenic mice is not known. Here we show that when mSOD1 mice were bred with
      mice lacking functional T cells or CD4+ T cells, motoneuron disease was
      accelerated, accompanied by unexpected attenuated morphological markers of
      gliosis, increased mRNA levels for proinflammatory cytokines and NOX2, and
      decreased levels of trophic factors and glial glutamate transporters. Bone marrow
      transplants reconstituted mice with T cells, prolonged survival, suppressed
      cytotoxicity, and restored glial activation. These results demonstrate for the
      first time in a model of chronic neurodegeneration that morphological activation
      of microglia and astroglia does not predict glial function, and that the presence
      of CD4+ T cells provides supportive neuroprotection by modulating the
      trophic/cytotoxic balance of glia. These glial/T-cell interactions establish a
      novel target for therapeutic intervention in ALS and possibly other
      neurodegenerative diseases.

PMID- 18809918
TI  - Ancient origin of the gene encoding involucrin, a precursor of the cross-linked
      envelope of epidermis and related epithelia.
AB  - The cross-linked (cornified) envelope is a characteristic product of terminal
      differentiation in the keratinocyte of the epidermis and related epithelia. This
      envelope contains many proteins of which involucrin was the first to be
      discovered and shown to become cross-linked by a cellular transglutaminase.
      Involucrin has evolved greatly in placental mammals, but retains the glutamine
      repeats that make it a good substrate for the transglutaminase. Until recently,
      it has been impossible to detect involucrin outside the placental mammals, but
      analysis of the GenBank and Ensembl databases that have become available since
      2006 reveals the existence of involucrin in marsupials and birds. We describe
      here the properties of these involucrins and the ancient history of their
      evolution.

PMID- 18809919
TI  - The mammary microenvironment alters the differentiation repertoire of neural stem
      cells.
AB  - A fundamental issue in stem cell biology is whether adult somatic stem cells are
      capable of accessing alternate tissue sites and continue functioning as stem
      cells in the new microenvironment. To address this issue relative to neurogenic
      stem cells in the mouse mammary gland microenvironment, we mixed wild-type
      mammary epithelial cells (MECs) with bona fide neural stem cells (NSCs) isolated
      from WAP-Cre/Rosa26R mice and inoculated them into cleared fat pads of
      immunocompromised females. Hosts were bred 6-8 weeks later and examined
      postinvolution. This allowed for mammary tissue growth, transient activation of
      the WAP-Cre gene, recombination, and constitutive expression of LacZ. The NSCs
      and their progeny contributed to mammary epithelial growth during ductal
      morphogenesis, and the Rosa26-LacZ reporter gene was activated by WAP-Cre
      expression during pregnancy. Some NSC-derived LacZ(+) cells expressed mammary
      specific functions, including milk protein synthesis, whereas others adopted
      myoepithelial cell fates. Thus, NSCs and their progeny enter mammary epithelium
      specific niches and adopt the function of similarly endowed mammary cells. This
      result supports the conclusion that tissue-specific signals emanating from the
      stroma and from the differentiated somatic cells of the mouse mammary gland can
      redirect the NSCs to produce cellular progeny committed to MEC fates.

PMID- 18809920
TI  - Selective expansion of a subset of exhausted CD8 T cells by alphaPD-L1 blockade.
AB  - Programmed death-1 (PD-1) regulates T cell exhaustion during chronic infections.
      Blocking the PD-1:PD-ligand (PD-L) pathway reinvigorates exhausted CD8 T cells.
      Exactly how blocking PD-1:PD-L interactions improves T cell immunity, however,
      remains unclear. PD-1:PD-L blockade could reprogram all exhausted T cells to
      become antiviral effectors. Alternatively, this blockade might selectively expand
      a subset of exhausted T cells. We have identified two subpopulations of exhausted
      CD8 T cells during chronic viral infection in mice. One subset of exhausted CD8 T
      cells is rescued by alphaPD-L1 blockade, whereas the other subset appears more
      terminally differentiated and responds poorly to PD-1:PD-L blockade. Blocking PD
      1:PD-L interactions reduces spontaneous apoptosis and enhances expansion and
      protective immunity of the rescuable subset, but not the more terminally
      differentiated subset of exhausted CD8 T cells. These results have implications
      for predicting clinical responses to PD-1-based therapeutic interventions and for
      understanding T cell dynamics during persisting infections.

PMID- 18809921
TI  - NF-IL6 (C/EBPbeta) induces HIV-1 replication by inhibiting cytidine deaminase
      APOBEC3G.
AB  - T cell activation is crucial for the productive HIV-1 infection of primary T
      cells; however, little is known about the host molecules involved in this
      process. We show that the host transcription factor NF-IL6 (also called
      C/EBPbeta) renders primary CD4(+) T cells highly permissive for HIV-1
      replication. NF-IL6 facilitates reverse transcription of the virus by binding to
      and inhibiting the antiviral cytidine deaminase APOBEC3G. A mutation in NF-IL6 at
      Ser-288 weakened its binding to APOBEC3G and strongly inhibited HIV-1
      replication. NF-IL6 also induced the replication of a Vif-deficient strain of HIV
      1 in nonpermissive HUT78 cells. These data indicate that NF-IL6 is a natural
      inhibitor of APOBEC3G that facilitates HIV-1 replication. Host factors, such as
      NF-IL6, that are involved in early HIV-1 replication are potential targets for
      anti-HIV-1 therapy. Our findings shed light on the activation of HIV-1
      replication by T cell host molecules and reveal a unique regulation of DNA
      deamination by APOBEC3G and NF-IL6.

PMID- 18809922
TI  - Distinct sets of alphabeta TCRs confer similar recognition of tumor antigen NY
      ESO-1157-165 by interacting with its central Met/Trp residues.
AB  - Naturally acquired immune responses against human cancers often include CD8(+) T
      cells specific for the cancer testis antigen NY-ESO-1. Here, we studied T cell
      receptor (TCR) primary structure and function of 605 HLA-A*0201/NY-ESO-1(157-165)
      specific CD8 T cell clones derived from five melanoma patients. We show that an
      important proportion of tumor-reactive T cells preferentially use TCR AV3S1/BV8S2
      chains, with remarkably conserved CDR3 amino acid motifs and lengths in both
      chains. All remaining T cell clones belong to two additional sets expressing BV1
      or BV13 TCRs, associated with alpha-chains with highly diverse VJ usage, CDR3
      amino acid sequence, and length. Yet, all T cell clonotypes recognize tumor
      antigen with similar functional avidity. Two residues, Met-160 and Trp-161,
      located in the middle region of the NY-ESO-1(157-165) peptide, are critical for
      recognition by most of the T cell clonotypes. Collectively, our data show that a
      large number of alphabeta TCRs, belonging to three distinct sets (AVx/BV1,
      AV3/BV8, AVx/BV13) bind pMHC with equal antigen sensitivity and recognize the
      same peptide motif. Finally, this in-depth study of recognition of a self-antigen
      suggests that in part similar biophysical mechanisms shape TCR repertoires toward
      foreign and self-antigens.

PMID- 18809923
TI  - Unconscious processing dissociates along categorical lines.
AB  - Visual object recognition is subserved by ventral temporal and occipital regions
      of the brain. Regions comprising the dorsal visual pathway have not been
      considered relevant for object recognition, despite strong categorical biases for
      tool-related information in those regions. Here, we show that dorsal stream
      processes influence object categorization. We used two techniques to render prime
      pictures invisible: continuous flash suppression (CFS), which obliterates input
      into ventral temporal regions, but leaves dorsal stream processes largely
      unaffected, and backward masking (BM), which allows suppressed information to
      reach both ventral and dorsal stream structures. Categorically congruent primes
      suppressed under CFS facilitate categorization of tools but have no effect on
      nonmanipulable objects; in contrast, primes rendered invisible through BM
      facilitate target categorization for both tools and nonmanipulable things. Our
      findings demonstrate that information computed by the dorsal stream is used in
      object categorization, but only for a category of manipulable objects.

PMID- 18809924
TI  - Human gene therapy for RPE65 isomerase deficiency activates the retinoid cycle of
      vision but with slow rod kinetics.
AB  - The RPE65 gene encodes the isomerase of the retinoid cycle, the enzymatic pathway
      that underlies mammalian vision. Mutations in RPE65 disrupt the retinoid cycle
      and cause a congenital human blindness known as Leber congenital amaurosis (LCA).
      We used adeno-associated virus-2-based RPE65 gene replacement therapy to treat
      three young adults with RPE65-LCA and measured their vision before and up to 90
      days after the intervention. All three patients showed a statistically
      significant increase in visual sensitivity at 30 days after treatment localized
      to retinal areas that had received the vector. There were no changes in the
      effect between 30 and 90 days. Both cone- and rod-photoreceptor-based vision
      could be demonstrated in treated areas. For cones, there were increases of up to
      1.7 log units (i.e., 50 fold); and for rods, there were gains of up to 4.8 log
      units (i.e., 63,000 fold). To assess what fraction of full vision potential was
      restored by gene therapy, we related the degree of light sensitivity to the level
      of remaining photoreceptors within the treatment area. We found that the
      intervention could overcome nearly all of the loss of light sensitivity resulting
      from the biochemical blockade. However, this reconstituted retinoid cycle was not
      completely normal. Resensitization kinetics of the newly treated rods were
      remarkably slow and required 8 h or more for the attainment of full sensitivity,
      compared with <1 h in normal eyes. Cone-sensitivity recovery time was rapid.
      These results demonstrate dramatic, albeit imperfect, recovery of rod- and cone
      photoreceptor-based vision after RPE65 gene therapy.

PMID- 18809925
TI  - The "fire stick farming" hypothesis: Australian Aboriginal foraging strategies,
      biodiversity, and anthropogenic fire mosaics.
AB  - Aboriginal burning in Australia has long been assumed to be a "resource
      management" strategy, but no quantitative tests of this hypothesis have ever been
      conducted. We combine ethnographic observations of contemporary Aboriginal
      hunting and burning with satellite image analysis of anthropogenic and natural
      landscape structure to demonstrate the processes through which Aboriginal burning
      shapes arid-zone vegetational diversity. Anthropogenic landscapes contain a
      greater diversity of successional stages than landscapes under a lightning fire
      regime, and differences are of scale, not of kind. Landscape scale is directly
      linked to foraging for small, burrowed prey (monitor lizards), which is a
      specialty of Aboriginal women. The maintenance of small-scale habitat mosaics
      increases small-animal hunting productivity. These results have implications for
      understanding the unique biodiversity of the Australian continent, through time
      and space. In particular, anthropogenic influences on the habitat structure of
      paleolandscapes are likely to be spatially localized and linked to less mobile,
      "broad-spectrum" foraging economies.

PMID- 18809926
TI  - Disulfide locking a sodium channel voltage sensor reveals ion pair formation
      during activation.
AB  - The S4 transmembrane segments of voltage-gated ion channels move outward on
      depolarization, initiating a conformational change that opens the pore, but the
      mechanism of S4 movement is unresolved. One structural model predicts sequential
      formation of ion pairs between the S4 gating charges and negative charges in
      neighboring S2 and S3 transmembrane segments during gating. Here, we show that
      paired cysteine substitutions for the third gating charge (R3) in S4 and D60 in
      S2 of the bacterial sodium channel NaChBac form a disulfide bond during
      activation, thus "locking" the S4 segment and inducing slow inactivation of the
      channel. Disulfide locking closely followed the kinetics and voltage dependence
      of activation and was reversed by hyperpolarization. Activation of D60C:R3C
      channels is favored compared with single cysteine mutants, and mutant cycle
      analysis revealed strong free-energy coupling between these residues, further
      supporting interaction of R3 and D60 during gating. Our results demonstrate
      voltage-dependent formation of an ion pair during activation of the voltage
      sensor in real time and suggest that this interaction catalyzes S4 movement and
      channel activation.

PMID- 18809927
TI  - Nanoparticle size and surface properties determine the protein corona with
      possible implications for biological impacts.
AB  - Nanoparticles in a biological fluid (plasma, or otherwise) associate with a range
      of biopolymers, especially proteins, organized into the "protein corona" that is
      associated with the nanoparticle and continuously exchanging with the proteins in
      the environment. Methodologies to determine the corona and to understand its
      dependence on nanomaterial properties are likely to become important in
      bionanoscience. Here, we study the long-lived ("hard") protein corona formed from
      human plasma for a range of nanoparticles that differ in surface properties and
      size. Six different polystyrene nanoparticles were studied: three different
      surface chemistries (plain PS, carboxyl-modified, and amine-modified) and two
      sizes of each (50 and 100 nm), enabling us to perform systematic studies of the
      effect of surface properties and size on the detailed protein coronas. Proteins
      in the corona that are conserved and unique across the nanoparticle types were
      identified and classified according to the protein functional properties.
      Remarkably, both size and surface properties were found to play a very
      significant role in determining the nanoparticle coronas on the different
      particles of identical materials. We comment on the future need for scientific
      understanding, characterization, and possibly some additional emphasis on
      standards for the surfaces of nanoparticles.

PMID- 18809928
TI  - Historical DNA analysis reveals living descendants of an extinct species of
      Galapagos tortoise.
AB  - Giant tortoises, a prominent symbol of the Galapagos archipelago, illustrate the
      influence of geological history and natural selection on the diversification of
      organisms. Because of heavy human exploitation, 4 of the 15 known species
      (Geochelone spp.) have disappeared. Charles Darwin himself detailed the intense
      harvesting of one species, G. elephantopus, which once was endemic to the island
      of Floreana. This species was believed to have been exterminated within 15 years
      of Darwin's historic visit to the Galapagos in 1835. The application of modern
      DNA techniques to museum specimens combined with long-term study of a system
      creates new opportunities for identifying the living remnants of extinct taxa in
      the wild. Here, we use mitochondrial DNA and microsatellite data obtained from
      museum specimens to show that the population on Floreana was evolutionarily
      distinct from all other Galapagos tortoise populations. It was demonstrated that
      some living individuals on the nearby island of Isabela are genetically distinct
      from the rest of the island's inhabitants. Surprisingly, we found that these "non
      native" tortoises from Isabela are of recent Floreana ancestry and closely match
      the genetic data provided by the museum specimens. Thus, we show that the genetic
      line of G. elephantopus has not been completely extinguished and still exists in
      an intermixed population on Isabela. With enough individuals to commence a
      serious captive breeding program, this finding may help reestablish a species
      that was thought to have gone extinct more than a century ago and illustrates the
      power of long-term genetic analysis and the critical role of museum specimens in
      conservation biology.

PMID- 18809929
TI  - Adaptive changes in the transcription factor HoxA-11 are essential for the
      evolution of pregnancy in mammals.
AB  - Evolutionary change in gene regulation can result from changes in cis-regulatory
      elements, leading to differences in the temporal and spatial expression of genes
      or in the coding region of transcription factors leading to novel functions or
      both. Although there is a growing body of evidence supporting the importance of
      cis-regulatory evolution, examples of protein-mediated evolution of novel
      developmental pathways have not been demonstrated. Here, we investigate the
      evolution of prolactin (PRL) expression in endometrial cells, which is essential
      for placentation/pregnancy in eutherian mammals and is a direct regulatory target
      of the transcription factor HoxA-11. Here, we show that (i) endometrial PRL
      expression is a derived feature of placental mammals, (ii) the PRL regulatory
      gene HoxA-11 experienced a period of strong positive selection in the stem
      lineage of eutherian mammals, and (iii) only HoxA-11 proteins from placental
      mammals, including the reconstructed ancestral eutherian gene, are able to up
      regulate PRL from the promoter used in endometrial cells. In contrast, HoxA-11
      from the reconstructed therian ancestor, opossum, platypus, and chicken are
      unable to up-regulate PRL expression. These results demonstrate that the
      evolution of novel gene expression domains is not only mediated by the evolution
      of cis-regulatory elements but can also require evolutionary changes of
      transcription factor proteins themselves.

PMID- 18809930
TI  - Evolutionary linkage between eukaryotic cytokinesis and chloroplast division by
      dynamin proteins.
AB  - Chloroplasts have evolved from a cyanobacterial endosymbiont and been retained
      for more than 1 billion years by coordinated chloroplast division in multiplying
      eukaryotic cells. Chloroplast division is performed by ring structures at the
      division site, encompassing both the inside and the outside of the two envelopes.
      A part of the division machinery is derived from the cyanobacterial cytokinetic
      activity based on the FtsZ protein. In contrast, other parts of the division
      machinery involve proteins specific to eukaryotes, including a member of the
      dynamin family. Each member of the dynamin family is involved in the division or
      fusion of a distinct eukaryotic membrane system. To gain insight into the kind of
      ancestral dynamin protein and eukaryotic membrane activity that evolved to
      regulate chloroplast division, we investigated the functions of the dynamin
      proteins that are most closely related to chloroplast division proteins. These
      proteins in the amoeba Dictyostelium discoideum and Arabidopsis thaliana localize
      at the sites of cell division, where they are involved in cytokinesis. Our
      results suggest that the dynamin for chloroplast division is derived from that
      involved in eukaryotic cytokinesis. Therefore, the chloroplast division machinery
      is a mixture of bacterial and eukaryotic cytokinesis components, with the latter
      a key factor in the synchronization of endosymbiotic cell division with host cell
      division, thus helping to establish the permanent endosymbiotic relationship.

PMID- 18809931
TI  - Boundaries of Dachsous Cadherin activity modulate the Hippo signaling pathway to
      induce cell proliferation.
AB  - The conserved Hippo tumor suppressor pathway is a key signaling pathway that
      controls organ size in Drosophila. To date a signal transduction cascade from the
      Cadherin Fat at the plasma membrane into the nucleus has been discovered.
      However, how the Hippo pathway is regulated by extracellular signals is poorly
      understood. Fat not only regulates growth but also planar cell polarity, for
      which it interacts with the Dachsous (Ds) Cadherin, and Four-jointed (Fj), a
      transmembrane kinase that modulates the interaction between Ds and Fat. Ds and Fj
      are expressed in gradients and manipulation of their expression causes abnormal
      growth. However, how Ds and Fj regulate growth and whether they act through the
      Hippo pathway is not known. Here, we report that Ds and Fj regulate Hippo
      signaling to control growth. Interestingly, we found that Ds/Fj regulate the
      Hippo pathway through a remarkable logic. Induction of Hippo target genes is not
      proportional to the amount of Ds or Fj presented to a cell, as would be expected
      if Ds and Fj acted as traditional ligands. Rather, Hippo target genes are up
      regulated when neighboring cells express different amounts of Ds or Fj.
      Consistent with a model that differences in Ds/Fj levels between cells regulate
      the Hippo pathway, we found that artificial Ds/Fj boundaries induce extra cell
      proliferation, whereas flattening the endogenous Ds and Fj gradients results in
      growth defects. The Ds/Fj signaling system thus defines a cell-to-cell signaling
      mechanism that regulates the Hippo pathway, thereby contributing to the control
      of organ size.

PMID- 18809932
TI  - Separating "us" from "them": Neanderthal and modern human behavior.

PMID- 18809933
TI  - Plasmodium vivax resistance to chloroquine in Madagascar: clinical efficacy and
      polymorphisms in pvmdr1 and pvcrt-o genes.
AB  - No data were available concerning Plasmodium vivax resistance to chloroquine (CQ)
      in Madagascar. We investigated the therapeutic efficacy of CQ in P. vivax
      malaria, the prevalence of mutations in the pvcrt-o and pvmdr1 genes before
      treatment, and the association between mutant parasites and the clinical response
      of the patients to CQ treatment. Clinical isolates were collected at six sentinel
      sites located in the three epidemiological strata for malaria throughout
      Madagascar in 2006. Patients were enrolled, treated, and followed up according to
      the WHO 2001 guidelines for P. vivax infections. Sequencing was used to analyze
      polymorphisms of the pvcrt-o (exons 1 to 6) and pvmdr1 genes. The treatment
      failure rate, after adjustment for genotyping, was estimated at 5.1% for the 105
      patients included, ranging from zero in the South to 14.8% in the foothills of
      the Central Highlands. All samples were wild type for pvcrt-o but mutant for the
      pvmdr1 gene. Ten nonsynonymous mutations were found in the pvmdr1 gene, including
      five new mutations, four of which were present at low frequencies (1.3% to 7.5%)
      while the S513R mutation was present at a much higher frequency (96.3%). The
      other five mutations, including Y976F, had been described before and had
      frequencies of 97.8% to 100%. Our findings suggest that CQ-resistant P. vivax
      isolates are present in Madagascar, particularly in the foothills of the Central
      Highlands. The 976Y pvmdr1 mutation was found not to be useful for monitoring CQ
      resistance. Further efforts are required to develop suitable tools for monitoring
      drug resistance in P. vivax malaria.

PMID- 18809934
TI  - Gain-of-function mutations in the transcription factor MRR1 are responsible for
      overexpression of the MDR1 efflux pump in fluconazole-resistant Candida
      dubliniensis strains.
AB  - Candida dubliniensis, a yeast that is closely related to Candida albicans, can
      rapidly develop resistance to the commonly used antifungal agent fluconazole in
      vitro and in vivo during antimycotic therapy. Fluconazole resistance in C.
      dubliniensis is usually caused by constitutive overexpression of the MDR1 gene,
      which encodes a multidrug efflux pump of the major facilitator superfamily. The
      zinc cluster transcription factor Mrr1p has recently been shown to control MDR1
      expression in C. albicans in response to inducing stimuli, and gain-of-function
      mutations in the MRR1 gene result in constitutive upregulation of the MDR1 efflux
      pump. We identified a gene with a high degree of similarity to C. albicans MRR1
      (CaMRR1) in the C. dubliniensis genome sequence. When C. dubliniensis MRR1
      (CdMRR1) was expressed in C. albicans mrr1Delta mutants, it restored benomyl
      inducible MDR1 expression, demonstrating that CdMRR1 is the ortholog of CaMRR1.
      To investigate whether MDR1 overexpression in C. dubliniensis is caused by
      mutations in MRR1, we sequenced the MRR1 alleles from a fluconazole-resistant,
      clinical C. dubliniensis isolate and a matched, fluconazole-susceptible isolate
      from the same patient as well as those from four in vitro-generated, fluconazole
      resistant C. dubliniensis strains derived from two different C. dubliniensis
      isolates. We found that all five resistant strains contained single nucleotide
      substitutions or small in-frame deletions that resulted in amino acid changes in
      Mrr1p. Expression of these mutated alleles in C. albicans resulted in the
      constitutive activation of the MDR1 promoter and multidrug resistance. Therefore,
      mutations in MRR1 are the major cause of MDR1 upregulation in both C. albicans
      and C. dubliniensis, demonstrating that the transcription factor Mrr1p plays a
      central role in the development of drug resistance in these human fungal
      pathogens.

PMID- 18809935
TI  - Tet 42, a novel tetracycline resistance determinant isolated from deep
      terrestrial subsurface bacteria.
AB  - Tet 42, a novel tetracycline resistance determinant from deep subsurface
      bacteria, was characterized and found to have a 30% sequence similarity to
      TetA(Z). The protein is a putative efflux pump that shares characteristics with
      previously characterized pumps, including a divergently transcribed TetR
      repressor, a conserved GxxSDRxGRR motif, and transmembrane domains.

PMID- 18809936
TI  - Genetic heterogeneity in pbp genes among clinically isolated group B Streptococci
      with reduced penicillin susceptibility.
AB  - The recent emergence of group B streptococcal isolates exhibiting increased
      penicillin MICs at the Funabashi Municipal Medical Center and other hospitals in
      Japan prompted a comparative analysis of the penicillin-binding proteins (PBPs)
      from those strains with the PBPs from penicillin-susceptible strains comprising
      four neonatal invasive strains isolated from 1976 to 1988 and two recent
      isolates. The PBP sequences of the penicillin-susceptible strains were highly
      conserved, irrespective of their isolation date. Of six strains with reduced
      susceptibility to penicillin (penicillin MICs, 0.25 to 0.5 mug/ml), strains R1,
      R2, R5, and R6 shared a unique set of five amino acid substitutions, including
      V405A adjacent to the (402)SSN(404) motif in PBP 2X and one in PBP 2B. The
      remaining two strains, R3 and R4, shared several substitutions, including Q557E
      adjacent to the (552)KSG(554) motif in PBP 2X, in addition to the substitutions
      in PBP 2B, which are commonly found among penicillin-insusceptible strains.
      Strains R7 and R8, which had a penicillin MIC of 1 mug/ml, shared a unique set of
      eight amino acid substitutions (two in PBP 2X; two in PBP 2B, including G613R
      adjacent to the (614)KTG(616) motif; three in PBP 1A; and one in PBP 2A), and the
      Q557E substitution in PBP 2X was common to R3 and R4. The binding of Bocillin FL
      was reduced or not detected in some PBPs, including PBP 2X of penicillin
      insusceptible strains, but no significant reduction in the level of pbp2x
      transcription was found in such strains. The results of phylogenetic comparative
      analyses imply the absence of epidemic penicillin-insusceptible strains, and
      several genetic lineages of penicillin-insusceptible strains have been
      independently emerging through the accumulation of mutations in their pbp genes,
      especially in pbp2x.

PMID- 18809937
TI  - Antifungal activities of human beta-defensins HBD-1 to HBD-3 and their C-terminal
      analogs Phd1 to Phd3.
AB  - The activities of defensins HBD-1, HBD-2, and HBD-3 and their C-terminal analogs
      Phd1, Phd2, and Phd3 against Candida albicans were investigated. Phd1 to Phd3
      showed lower-level activities than HBD-1 to HBD-3, although metabolic inhibitors
      did not render Phd1 to Phd3 inactive. Their activities were also less salt
      sensitive than those of HBD-1 to HBD-3. Confocal microscope images indicated that
      the initial site of action was the fungal membrane.

PMID- 18809938
TI  - In vitro and in vivo validation of ligA and tarI as essential targets in
      Staphylococcus aureus.
AB  - A conditional expression system has been developed using the isopropyl-beta-d
      thiogalactopyranoside (IPTG)-inducible Pspac promoter to validate essential genes
      of Staphylococcus aureus in vivo. The system has been applied to prove the
      essentiality of ligA and to evaluate the function of tarI, which was found to be
      essential in vitro but not in vivo.

PMID- 18809939
TI  - High prevalence of plasmid-mediated quinolone resistance genes qnr and aac(6')-Ib
      cr in clinical isolates of Enterobacteriaceae from nine teaching hospitals in
      China.
AB  - Quinolone resistance is an emerging problem in China. To investigate the
      prevalence of the plasmid-mediated quinolone resistance genes qnr and aac(6')-Ib
      cr, a total of 265 clinical isolates of Escherichia coli, Klebsiella pneumoniae,
      Citrobacter freundii, and Enterobacter cloacae with ciprofloxacin MICs of > or
      =0.25 microg/ml were screened at nine teaching hospitals in China. The qnrA,
      qnrB, qnrS, and aac(6')-Ib genes were detected by PCR. The aac(6')-Ib-cr gene was
      further identified by digestion with BtsCI and/or direct sequencing. The qnr gene
      was present in significantly smaller numbers of isolates with cefotaxime MICs of
      <2 microg/ml than isolates with higher MICs (> or =2.0 microg/ml) (20.6% and
      42.1%, respectively; P < 0.05). aac(6')-Ib-cr was present in 17.0% of the
      isolates tested, and 7.9% of the isolates carried both the qnr and the aac(6')-Ib
      cr genes. Among the isolates with cefotaxime MICs of > or =2.0 microg/ml, qnr and
      aac(6')-Ib-cr were present in 65.7% and 8.6% of E. cloacae isolates,
      respectively; 65.5% and 21.8% of K. pneumoniae isolates, respectively; 63.3% and
      26.7% of C. freundii isolates, respectively; and 6.5% and 16.9% of E. coli
      isolates, respectively. The 20 transconjugants showed 16- to 128-fold increases
      in ciprofloxacin MICs, 14 showed 16- to 2,000-fold increases in cefotaxime MICs,
      and 5 showed 8- to 32-fold increases in cefoxitin MICs relative to those of the
      recipient due to the cotransmission of bla(CTX-M-14), bla(CTX-M-3), bla(DHA-1),
      bla(SHV-2), and bla(SHV-12) with the qnr and aac(6')-Ib-cr genes. Southern
      hybridization analysis showed that these genes were located on large plasmids of
      different sizes (53 to 193 kb). These findings indicate the high prevalence of
      qnr and aac(6')-Ib-cr in members of the family Enterobacteriaceae and the
      widespread dissemination of multidrug resistance in China.

PMID- 18809940
TI  - Safety and efficacy of enfuvirtide in combination with darunavir-ritonavir and an
      optimized background regimen in treatment-experienced human immunodeficiency
      virus-infected patients: the below the level of quantification study.
AB  - Enfuvirtide is the first fusion and entry inhibitor approved for use for the
      treatment of human immunodeficiency virus (HIV) type 1 infection and as such
      represents a novel class of agents. For the population of patients experienced
      with three antiretroviral classes, enfuvirtide provides an additional option for
      treatment. This prospective, open-label, 24-week, single-arm trial assessed the
      efficacy and safety of enfuvirtide (90 mg injected subcutaneously twice daily) in
      combination with darunavir-ritonavir (600/100 mg administered orally twice daily)
      in triple-antiretroviral-class-experienced adults failing their current regimen.
      The primary efficacy endpoint was the proportion of participants with plasma HIV
      RNA loads of <50 copies/ml. Other virological and immunological measures were
      also evaluated, as were the effects of the baseline viral coreceptor tropism and
      darunavir phenotype sensitivity scores on the outcomes. At week 24, 60.3%, 72.5%,
      and 84.0% of 131 participants achieved viral loads of <50 copies/ml and <400
      copies/ml and a change from the baseline load of > or =1 log(10) copies/ml,
      respectively. A baseline viral load of < or =5 log(10) copies/ml was a
      significant predictor of achieving a viral load of <50 copies/ml at 24 weeks;
      however, neither background genotype sensitivity nor darunavir phenotype
      sensitivity was a significant predictor of the achievement of viral loads of <50
      copies/ml. Although these findings are limited by the relatively small numbers of
      participants with darunavir susceptibility changes of > or =10-fold, they suggest
      that combining enfuvirtide and darunavir-ritonavir with an optimized background
      regimen in triple-class experienced participants naive to these agents can result
      in positive virological and immunological responses regardless of most baseline
      parameters.

PMID- 18809941
TI  - Inhibition of Bacillus anthracis spore outgrowth by nisin.
AB  - The lantibiotic nisin has previously been reported to inhibit the outgrowth of
      spores from several Bacillus species. However, the mode of action of nisin
      responsible for outgrowth inhibition is poorly understood. By using B. anthracis
      Sterne 7702 as a model, nisin acted against spores with a 50% inhibitory
      concentration (IC(50)) and an IC(90) of 0.57 microM and 0.90 microM,
      respectively. Viable B. anthracis organisms were not recoverable from cultures
      containing concentrations of nisin greater than the IC(90). These studies
      demonstrated that spores lose heat resistance and become hydrated in the presence
      of nisin, thereby ruling out a possible mechanism of inhibition in which nisin
      acts to block germination initiation. Rather, germination initiation is requisite
      for the action of nisin. This study also revealed that nisin rapidly and
      irreversibly inhibits growth by preventing the establishment of oxidative
      metabolism and the membrane potential in germinating spores. On the other hand,
      nisin had no detectable effects on the typical changes associated with the
      dissolution of the outer spore structures (e.g., the spore coats, cortex, and
      exosporium). Thus, the action of nisin results in the uncoupling of two critical
      sequences of events necessary for the outgrowth of spores: the establishment of
      metabolism and the shedding of the external spore structures.

PMID- 18809942
TI  - Prospective study of fecal colonization by extended-spectrum-beta-lactamase
      producing Escherichia coli in neutropenic patients with cancer.
AB  - Fecal colonization by extended-spectrum-beta-lactamase-producing Escherichia coli
      in 912 stool samples collected from 154 neutropenic patients with cancer,
      hospitalized at two teaching institutions, was prospectively studied. Forty-nine
      (31.8%) patients were colonized, 22 of them at hospital admission. Most strains
      were clonally unrelated and carried a CTX-M-9 group enzyme.

PMID- 18809943
TI  - Piperacillin-tazobactam penetration into human pancreatic juice.
AB  - Piperacillin-tazobactam was administered as a single dose (4.5 g intravenous) to
      five patients with stabilized external pancreatic fistula. The penetration into
      pancreatic juice was prompt, and inhibitory concentrations were achieved and
      maintained for different periods (0.5 to 6 h) according to bacterial
      susceptibility and patients' characteristics. Piperacillin and tazobactam showed
      superimposable pharmacokinetics in both serum and pancreatic juice.

PMID- 18809944
TI  - Rationale for reading fluconazole MICs at 24 hours rather than 48 hours when
      testing Candida spp. by the CLSI M27-A2 standard method.
AB  - We investigated if CLSI M27-A2 Candida species breakpoints for fluconazole MIC
      are valid when read at 24 h. Analysis of a data set showed good correlation
      between 48- and 24-h MICs, as well as similar outcomes and pharmacodynamic
      efficacy parameters, except for isolates in the susceptible dose-dependent
      category, such as Candida glabrata.

PMID- 18809945
TI  - First countrywide survey of acquired metallo-beta-lactamases in gram-negative
      pathogens in Italy.
AB  - Metallo-beta-lactamases (MBLs) can confer resistance to most beta-lactams,
      including carbapenems. Their emergence in gram-negative pathogens is a matter of
      major concern. Italy was the first European country to report the presence of
      acquired MBLs in gram-negative pathogens and is one of the countries where MBL
      producers have been detected repeatedly. Here, we present the results of the
      first Italian nationwide survey of acquired MBLs in gram-negative pathogens. Of
      14,812 consecutive nonreplicate clinical isolates (12,245 Enterobacteriaceae
      isolates and 2,567 gram-negative nonfermenters) screened for reduced carbapenem
      susceptibility during a 4-month period (September to December 2004), 30 isolates
      (28 Pseudomonas aeruginosa isolates, 1 Pseudomonas putida isolate, and 1
      Enterobacter cloacae isolate) carried acquired MBL determinants. MBL producers
      were detected in 10 of 12 cities, with a predominance of VIM-type enzymes over
      IMP-type enzymes (4:1). Although having an overall low prevalence (1.3%) and
      significant geographical differences, MBL-producing P. aeruginosa strains
      appeared to be widespread in Italy, with a notable diversity of clones, enzymes,
      and integrons carrying MBL gene cassettes.

PMID- 18809946
TI  - Population pharmacokinetics of fluconazole in young infants.
AB  - Fluconazole is being increasingly used to prevent and treat invasive candidiasis
      in neonates, yet dosing is largely empirical due to the lack of adequate
      pharmacokinetic (PK) data. We performed a multicenter population PK study of
      fluconazole in 23- to 40-week-gestation infants less than 120 days of age. We
      developed a population PK model using nonlinear mixed effect modeling (NONMEM)
      with the NONMEM algorithm. Covariate effects were predefined and evaluated based
      on estimation precision and clinical significance. We studied fluconazole PK in
      55 infants who at enrollment had a median (range) weight of 1.02 (0.440 to 7.125)
      kg, a gestational age at birth (BGA) of 26 (23 to 40) weeks, and a postnatal age
      (PNA) of 2.3 (0.14 to 12.6) weeks. The final data set contained 357 samples;
      217/357 (61%) were collected prospectively at prespecified time intervals, and
      140/357 (39%) were scavenged from discarded clinical specimens. Fluconazole
      population PK was best described by a one-compartment model with covariates
      normalized to median values. The population mean clearance (CL) can be derived
      for this population by the equation CL (liter/h) equals 0.015 . (weight/1)(0.75)
      . (BGA/26)(1.739) . (PNA/2)(0.237) . serum creatinine (SCRT)(-4.896) (when SCRT
      is >1.0 mg/dl), and using a volume of distribution (V) (liter) of 1.024 .
      (weight/1). The relative standard error around the fixed effects point estimates
      ranged from 3 to 24%. CL doubles between birth and 28 days of age from 0.008 to
      0.016 and from 0.010 to 0.022 liter/kg/h for typical 24- and 32-week-gestation
      infants, respectively. This population PK model of fluconazole discriminated the
      impact of BGA, PNA, and creatinine on drug CL. Our data suggest that dosing in
      young infants will require adjustment for BGA and PNA to achieve targeted
      systemic drug exposures.

PMID- 18809947
TI  - Paying the price for eating ice cream: is excessive GLP-1 signaling in the brain
      the culprit?

PMID- 18809948
TI  - Negative cardiotropism by catestatin and its variants.

PMID- 18809950
TI  - Sonographic appearance of trigger fingers.
AB  - OBJECTIVE: The purpose of this study was to describe the sonographic appearance
      of the first annular (A1) pulley-flexor tendon complex in patients with trigger
      fingers. METHODS: Thirty-three trigger fingers in 33 patients were examined with
      a 7- to 15-MHz probe. A control group consisted of 20 patients without trigger
      fingers. The study included systematic measurement of the thickness of the A1
      pulley and a power Doppler assessment of the pulleys, tendons, and tendon
      sheaths. RESULTS: Thickening and hypoechogenicity of the A1 pulley were found in
      all patients with trigger fingers. Measurements of A1 pulley thickness were
      significantly different (P < .0001) between the groups without trigger fingers
      (mean, 0.5 mm; range, 0.4-0.6 mm) and with trigger fingers (mean, 1.8 mm; range,
      1.1-2.9 mm). Hypervascularization of the A1 pulley on power Doppler imaging was
      found in 91% of the trigger fingers but was never found in the healthy control
      group. Flexor tendinosis was found in 48% of the trigger fingers; tenosynovitis
      was found in 55%; and both were found in 39%. In the control group, tenosynovitis
      and tendinosis were not found. CONCLUSIONS: Thickening and hyper-vascularization
      of the A1 pulley are the hallmarks of trigger fingers on sonography. Other
      frequently observed features include distal flexor tendinosis and tenosynovitis.

PMID- 18809951
TI  - Low-intensity pulsed ultrasound-promoted bone healing is not entirely
      cyclooxgenase 2 dependent.
AB  - OBJECTIVE: The purpose of this study was to investigate whether low-intensity
      pulsed ultrasound (LIPUS) promotes bone healing through the cyclooxgenase 2 (COX
      2) pathway. METHODS: Each male Sprague Dawley rat (n = 48 total) in the study
      underwent bilateral drilled hole injury in the proximal tibiae. Then the animals
      were randomly assigned to 2 groups: a COX-2 inhibitor (COX-2in) group, treated
      with the selective COX-2 inhibitor rofecoxib (3 mg/kg/d), and a control (CON)
      group, treated with distilled water. Low-intensity pulsed ultrasound was applied
      to the injured site of a single limb of each rat for 20 min/d at a consistent
      intensity (30 mW/cm(2)) and frequency (1.5 MHz). Subsets of animals from both
      groups were killed after 3, 7, or 14 days of single-limb LIPUS treatment. Tissue
      sections were subjected to alcian blue staining, and the healing status was
      quantified according to a scoring system. RESULTS: After 3 and 7 days, the CON
      group's LIPUS-treated limbs had significantly higher healing scores than its
      nontreated limbs and the COX-2in group's LIPUS-treated limbs (P < .05).
      Interestingly, after the 14-day treatment, the COX-2in group's LIPUS-treated
      limbs had significantly higher healing scores than its nontreated limbs (P < .05)
      but showed no difference when compared with the CON group. CONCLUSIONS: Low
      intensity pulsed ultrasound did show accelerative efficacy on bone healing.
      Selective inhibition of COX-2 could delay but not entirely block the benefits of
      LIPUS on bone healing. Low-intensity ultrasound treatment could promote bone
      healing through other, non-COX-2-dependent, pathways.

PMID- 18809952
TI  - Sonographic differentiation of thyroid nodules with eggshell calcifications.
AB  - OBJECTIVE: The purpose of this study was to assess the role of known suspicious
      sonographic findings and to find other additional sonographic findings to
      differentiate benign and malignant thyroid nodules with "eggshell"
      calcifications. METHODS: Our Institutional Review Board approved this
      retrospective study, and informed consent was not required. We reviewed
      sonographic findings of thyroid nodules in 795 patients who underwent thyroid
      surgery in our institution between August 2006 and February 2007. Ninety-three
      thyroid nodules with eggshell calcifications in 92 patients were included in this
      study. Each lesion was evaluated for known suspicious sonographic criteria,
      including marked hypoechogenicity, irregular or microlobulated margins, and a
      taller-than-wide shape, as well as 2 additional sonographic findings: a
      hypoechoic halo and disruption of eggshell calcifications (halo and disrupted
      calcification rim). The sensitivity and specificity based on the sonographic
      criteria were calculated and compared among the 2 types of criteria. RESULTS:
      Among the 93 thyroid nodules, 59 were malignant and 34 were benign. The halo and
      disrupted calcification rim showed higher sensitivity (62.7% and 76.3%,
      respectively) than any of the known suspicious sonographic criteria (40.7%,
      35.6%, and 55.9%). The combination of both the halo and the disrupted
      calcification rim showed significantly higher sensitivity (93.2%) than the
      combination of the known suspicious sonographic criteria (78%; P < .05), although
      both had the same specificity (64.7%). CONCLUSIONS: In thyroid nodules with
      eggshell calcifications but no other calcifications, the findings of a peripheral
      halo and disruption of the eggshell calcifications may be more useful sonographic
      predictors of malignancy than hypoechogenicity, microlobulated margins, and a
      taller-than-wide shape.

PMID- 18809953
TI  - Sonographic features of the follicular variant of papillary thyroid carcinoma.
AB  - OBJECTIVE: The purpose of this study was to evaluate the sonographic findings of
      the follicular variant of papillary thyroid carcinoma (FVPTC) and to assess the
      role of preoperative fine-needle aspiration biopsy (FNAB). METHODS: The
      sonographic findings of 27 thyroid nodules in 26 patients (2 male and 24 female;
      mean age, 45 years) with surgically proven FVPTC were reviewed retrospectively.
      Findings were categorized according to the echogenicity, margin, shape, and
      presence of microcalcifications. Malignant findings included marked
      hypoechogenicity, irregular or microlobulated margins, a taller-than-wide shape,
      and microcalcifications. Thyroid nodules with a single malignant finding as
      described above were classified as malignant. All patients underwent
      sonographically guided FNAB, and the sensitivity of the cytologic results was
      calculated. RESULTS: Lesion sizes varied from 3 to 34 mm (mean, 15.2 mm), and
      lesions were most commonly solid (23 [85.2%]), hypoechoic (14 [51.9%]), and oval
      (17 [63%]) with well-defined margins (14 [51.9%]) and no microcalcifications (23
      [85.2%]). Eighteen lesions (66.7%) were correctly classified as malignant,
      whereas 9 (33.3%) were classified as benign on the basis of sonographic criteria.
      Twenty-four samples were adequate for cytologic examination, and 3 were
      inadequate. Twenty-one of 24 diagnostic cytologic results (87.5%) were suspicious
      for papillary carcinoma (5 of 21 [20.8%]) or malignant (16 of 21 [66.7%]),
      whereas 3 lesions (12.5%) had benign results. The sensitivity of FNAB was 77.8%
      (21 of 27). CONCLUSIONS: The follicular variant of papillary thyroid carcinoma
      tends to have relatively benign sonographic features, such as hypoechogenicity,
      well-defined margins, an oval shape, and no microcalcifications, but most lesions
      were correctly classified as malignant by both sonography and FNAB. The
      possibility of FVPTC should be considered when thyroid nodules with a relatively
      benign sonographic appearance have suspicious or malignant FNAB results.

PMID- 18809954
TI  - Evaluation of patients with suspected ureteral calculi using sonography as an
      initial diagnostic tool: how can we improve diagnostic accuracy?
AB  - OBJECTIVE: The purpose of this study was to evaluate the usefulness of sonography
      as an initial diagnostic tool in patients with suspected ureterolithiasis.
      METHODS: We performed a prospective study of 318 patients with suspected ureteral
      stones over a 14-month period. All patients underwent sonography after fasting
      for 8 hours and bladder filling. If no cause of the flank pain was found by
      sonography, computed tomography or intravenous urography was performed
      immediately to confirm the absence of ureteral stones. RESULTS: We found
      urolithiasis with sonography in 291 of 296 patients with confirmed urolithiasis.
      The 5 remaining cases were identified after non-contrast-enhanced computed
      tomography (n = 3), intravenous urography (n = 1), or the passage of a stone (n =
      1, pregnant patient). We detected 313 calculi in the 291 patients with sonography
      as follows: 307 ureteral calculi in 285 patients, 5 urinary bladder calculi that
      were probably passed from the ureter in 5 patients, and 1 urethral calculus. The
      locations of the 313 calculi in the 291 patients with a sonographic diagnosis
      were as follows: 21 were in the ureteropelvic junction, 96 in the proximal half
      of the ureter, 69 in the distal half of the ureter, 121 in the ureterovesical
      junction, 5 in the urinary bladder, and 1 in the urethra. Hydronephrosis was seen
      in 200 of the 291 patients with calculi identified by sonography (68.7%).
      Twinkling artifacts helped confirm the presence of tiny calculi in 184 of the 214
      calculi (86%). CONCLUSIONS: Sonography can be used as an initial diagnostic tool
      in patients with suspected ureterolithiasis.

PMID- 18809955
TI  - Three-dimensional ultrasonography-based virtual cystoscopy of the pediatric
      urinary bladder: a preliminary report on feasibility and potential value.
AB  - OBJECTIVE: The purpose of this study was to validate the feasibility and
      potential of 3-dimensional ultrasonography (3DUS)-based virtual cystoscopy in the
      pediatric urinary bladder. METHODS: Twenty patients (age range, newborn-14 years)
      underwent urinary tract ultrasonography and 3DUS of the urinary bladder. From
      this data set, virtual cystoscopy was reconstructed for visualization of the
      inner bladder surface. Three-dimensional ultrasonography was compared with 2
      dimensional ultrasonographic (2DUS) findings, voiding cystourethrography (VCUG)
      results, and reports from cystoscopy or surgery when available. RESULTS: Three
      dimensional ultrasonography was feasible in all patients. Data quality was
      sufficient for virtual cystoscopy without major motion artifacts. The 3DUS
      results matched all other findings; particularly, 3DUS superiorly visualized the
      ureteral ostium and the bladder neck configuration; in 5 patients, 3DUS depicted
      pathologically shaped ostia not detected by 2DUS. This correlated with the
      presence of vesicoureteral reflux on VCUG. Performing virtual cystoscopy added 1
      minute to the investigation time (range, 0.5-2 minutes) and 3 minutes for
      postprocessing and viewing (range, 2-5 minutes). CONCLUSIONS: Three-dimensional
      ultrasonography-based virtual cystoscopy is feasible in the pediatric urinary
      bladder without sedation. It reveals surface information not accessible by 2DUS,
      improving detection of pathologic conditions such as atypically shaped ureteral
      ostia. Three-dimensional ultrasonography-based cystoscopy may become a valuable
      adjunct to 2DUS of the pediatric urinary tract, improving selection criteria for
      further imaging such as VCUG, and potentially may help reduce the need for
      endoscopic cystoscopy. However, these preliminary results still have to be
      confirmed in prospective studies with larger patient numbers.

PMID- 18809956
TI  - Outcome prediction for treatment of tubal pregnancy using an intramuscular
      methotrexate protocol.
AB  - OBJECTIVE: The purpose of this study was to determine the outcome predictors of
      intramuscular methotrexate therapy for tubal pregnancy. METHODS: This
      retrospective study was approved by our Institutional Review Board. Fifty-five
      consecutive women (mean age, 31 years; range, 18-45 years) who were treated with
      intramuscular methotrexate therapy for tubal pregnancy were retrospectively
      reviewed. Clinical data (maternal age, gestational age, and serum beta-human
      chorionic gonadotropin [beta-hCG] level) and transvaginal sonographic findings
      (size, gross appearance, presence of a gestational product or heartbeat, and
      amount of the fluid collection) were assessed as potential predictors of the
      treatment outcome. The Fisher exact test was used for categorical variables, and
      the Wilcoxon signed rank sum test was used for continuous variables. Treatment
      failure was defined as the need for surgical intervention. RESULTS: Women with
      successful treatment differed from women with unsuccessful treatment with respect
      to the serum beta-hCG level, the gross appearance of tubal pregnancy, and the
      presence of a gestational product such as a yolk sac or embryo (P <.001; P = .01;
      and P =.008, respectively). All of the tubal pregnancies with a gestational
      product appeared as a tubal ring on transvaginal sonography. A high serum beta
      hCG level of greater than 2390 mIU/mL and a transvaginal sonographic appearance
      of a tubal ring were the important predictors associated with failure of
      intramuscular methotrexate therapy for tubal pregnancy. CONCLUSIONS: Measurement
      of the serum beta-hCG level and evaluation of the transvaginal sonographic
      appearance of tubal pregnancy are helpful for predicting treatment outcomes in
      women who receive intramuscular methotrexate therapy for tubal pregnancy.

PMID- 18809957
TI  - Comparison of the risk of malignancy index and self-constructed logistic
      regression models in preoperative evaluation of adnexal masses.
AB  - OBJECTIVE: The aim of this study was to evaluate women with adnexal masses in the
      preoperative period by creating 2 logistic regression models, 1 including
      sonographic morphologic characteristics and the other including both morphologic
      and color Doppler characteristics, to compare the diagnostic accuracy of these 2
      models with the risk of malignancy index (RMI). METHODS: This prospective study
      included 38 malignant, 7 borderline, and 244 benign ovarian masses. The
      menopausal status, presence of septa, presence of papillary projections, location
      of the tumor, presence of ascites, presence of metastases, cancer antigen 125
      level, tumor volume, septa thickness, and percentage of the solid component were
      included in the initial analysis. A second regression analysis was performed with
      the addition of Doppler parameters (location of blood flow and lowest resistive
      index) in the data set. Diagnostic performance of the 2 regression models and RMI
      were described and compared by generating receiver operating characteristic
      curves for each model. RESULTS: The area under the curve values for the
      morphologic model (model 1), Doppler model (model 2), and RMI were 0.907, 0.971,
      and 0.889, respectively. Significance levels of model 1 and the RMI were similar
      (P = .23), whereas model 2 had a significantly higher area under the curve
      compared with both model 1 (P = .037) and the RMI (P = .018). CONCLUSIONS: The
      addition of Doppler parameters in the regression model significantly increases
      the predictive performance. Nevertheless, in low-resource settings, the RMI
      remains the method of choice for distinguishing adnexal masses and referral to
      gynecologic oncology clinics.

PMID- 18809958
TI  - Sonorectovaginography: a new sonographic technique for imaging of the posterior
      compartment of the pelvis.
AB  - OBJECTIVE: We describe the use of a new sonographic technique for imaging of the
      posterior compartment of the pelvis: sonorectovaginography. METHODS:
      Sonorectovaginography uses instillation of fluids (saline solution and ultrasound
      gel) in the vagina, pouch of Douglas, and rectum for the purpose of creating
      acoustic interfaces between the vagina, cervix, rectum, and pouch of Douglas. We
      performed sonorectovaginography in a woman with chronic pelvic pain during
      laparoscopy. Urinary catheters were introduced into the rectum and vagina.
      Sterile saline solution was introduced into the abdominal cavity through a
      laparoscopic trocar and in the rectum via a rectal catheter. The transvaginal
      probe was then inserted, and sterile ultrasound gel was introduced into the
      vagina through the vaginal catheter under sonographic guidance. RESULTS:
      Sonorectovaginography has helped us create acoustic interfaces and enhanced
      simultaneous visualization of the vaginal walls, posterior vaginal fornix,
      retrocervical area, rectovaginal septum, rectal wall, and pouch of Douglas.
      CONCLUSIONS: Imaging of the posterior compartment of the pelvis is of paramount
      importance for identification of potentially difficult endometriosis cases, such
      as those complicated by obliteration of the pouch of Douglas or infiltration of
      the retrocervical area, rectovaginal septum, or vaginal or rectal wall.
      Sonorectovaginography may prove helpful in evaluating this compartment of the
      pelvis in women with suspected deep endometriosis. Its reproducibility,
      tolerability, and accuracy, however, need to be validated prospectively, and
      normative data for the rectovaginal septum also need to be established.

PMID- 18809959
TI  - Sonographically guided carpal tunnel injections: the ulnar approach.
AB  - OBJECTIVE: The purpose of this report is to describe a new sonographically guided
      technique for carpal tunnel injections using an ulnar approach. METHODS:
      Previously published sonographically guided techniques for carpal tunnel
      injections were reviewed. Described approaches were noted to be technically
      challenging because of the need to perform long-axis imaging of the carpal
      tunnel, short-axis (out-of-plane) imaging of the needle, or both. RESULTS: We
      developed and herein describe the ulnar approach for sonographically guided
      carpal tunnel injections. Advantages of this approach include transverse imaging
      of the carpal tunnel, long-axis (in-plane) imaging of the needle, and versatility
      in targeting structures within the carpal tunnel. CONCLUSIONS: Clinicians should
      consider the ulnar-sided approach when performing sonographically guided carpal
      tunnel injections.

PMID- 18809960
TI  - High-definition flow Doppler ultrasonographic technique to assess hepatic
      vasculature compared with color or power Doppler ultrasonography: preliminary
      experience.
AB  - OBJECTIVE: The purpose of this study was to introduce a new high-definition flow
      (HDF) Doppler technique and to compare its performance with those of color
      Doppler ultrasonography (CDU) and power Doppler ultrasonography (PDU) for
      assessment of hepatic vasculature in native and transplanted livers. METHODS:
      High-definition flow was invented as a high-resolution bidirectional PDU
      technique. We obtained CDU, PDU, and HDF images of the hepatic artery (HA),
      portal vein (PV), and hepatic vein from 60 patients. They were divided into 2
      groups: a liver transplantation group (group 1, n = 10) and a native liver group
      (group 2, n = 50). Two radiologists independently reviewed the cine images and
      graded them using a 4-point scale in terms of the clarity of the vessel margin
      and degree of depiction of the HA, flow filling, and flash artifacts. The degree
      of differentiation between the HA and PV was also evaluated. Flow directionality
      was recorded, and interobserver agreement was finally analyzed. RESULTS: Moderate
      to almost perfect agreement was achieved between radiologists for all parameters
      of each ultrasonographic technique. High-definition flow was significantly
      superior to both CDU and PDU with respect to all analyzed items except the degree
      of flash artifacts (P < .05). With regard to flash artifacts, CDU was
      significantly better than either PDU or HDF. High-definition flow provided
      directional information, as did CDU. CONCLUSIONS: The HDF technique provides
      better resolution for depicting hepatic vessels as well as their margins with
      less blooming compared with conventional Doppler ultrasonography in both native
      and transplanted liver. It also provides solid directional flow information. One
      point of concern, however, is the frequency of flash artifacts compared with that
      on CDU.

PMID- 18809961
TI  - Testicular microlithiasis in a 2-year-old boy with pseudoxanthoma elasticum.

PMID- 18809962
TI  - Sonographic detection of spontaneous pneumomediastinum.

PMID- 18809963
TI  - Contrast-enhanced ultrasonographic findings in a brucellar hepatic abscess.

PMID- 18809964
TI  - Subendothelial carotid hematoma after fine-needle aspiration biopsy of a solitary
      thyroid nodule.

PMID- 18809965
TI  - Role of sonography in the evaluation of unstable os acromiale.

PMID- 18809966
TI  - Lymphoma involving the ulnar nerve: sonographic findings.

PMID- 18809967
TI  - Metastatic gestational trophoblastic disease following a complete hydatidiform
      mole coexistent with an anencephalic fetus diagnosed at 10 weeks' gestation.

PMID- 18809968
TI  - Innominate steal phenomenon: color and spectral Doppler sonographic findings.

PMID- 18809969
TI  - Potent anticarcinoma activity of the humanized anti-CD70 antibody h1F6 conjugated
      to the tubulin inhibitor auristatin via an uncleavable linker.
AB  - PURPOSE: The antitubulin agent monomethyl auristatin F (MMAF) induces potent
      antitumor effects when conjugated via protease cleavable linkers to antibodies
      targeting internalizing, tumor-specific cell surface antigens. Humanized 1F6
      (h1F6) is a humanized monoclonal antibody targeting CD70, a member of the tumor
      necrosis factor family that is expressed on hematologic malignancies and
      carcinomas. Here, we tested h1F6-maleimidocaproyl (mc) MMAF conjugates,
      consisting of an uncleavable mc linker, for their ability to interfere with the
      growth of CD70-positive carcinomas. EXPERIMENTAL DESIGN: To evaluate the optimal
      drug per antibody ratio, we conjugated either four or eight MMAF molecules to the
      cysteines that comprise the interchain disulfides of h1F6 and determined
      antitumor activities in vitro and in xenografted mice. The tumor types tested
      included glioblastoma, patient-derived renal cell carcinoma (RCC) cell isolates,
      and standard RCC tumor cell lines. RESULTS: All h1F6-mcMMAF conjugates potently
      interfered with the growth of all carcinomas in vitro and resulted in complete
      responses of RCC tumors implanted orthotopically or s.c. in mice. In vitro, h1F6
      mcMMAF(8) was generally more potent than h1F6-mcMMAF(4). However, h1F6-mcMMAF(4)
      displayed equal or better efficacy than h1F6-mcMMAF(8) when administered to tumor
      bearing mice. CONCLUSIONS: We showed that h1F6-mcMMAF conjugates inhibited the
      growth of human carcinomas and that increased drug loading, while improving
      potency in vitro, did not substantially affect the pharmacodynamic and
      pharmacokinetic properties in vivo. Based on these findings, h1F6-mcMMAF(4),
      designated SGN-75, has been identified as a potential antibody-drug conjugate for
      clinical development.

PMID- 18809970
TI  - Expression of heparanase in renal cell carcinomas: implications for tumor
      invasion and prognosis.
AB  - PURPOSE: Heparanase activity has been detected in many malignant tumors, showing
      a correlation with the metastatic potential. The present study was undertaken to
      investigate the expression of heparanase and its prognostic significance in renal
      cell carcinomas (RCC). EXPERIMENTAL DESIGN: Nineteen RCCs and 6 nonneoplastic
      renal tissues were analyzed for heparanase mRNA expression by real-time PCR.
      Heparanase protein expression was semiquantitatively investigated by
      immunohistochemistry in 70 RCCs. Involvement of heparanase in the invasiveness of
      RCC cell lines, 786-O and Caki-2 cells, was examined by down-regulating the gene
      expression with small interfering RNA (siRNA) using the Matrigel invasion assay.
      RESULTS: The expression level of heparanase mRNA was significantly higher in
      clear cell RCCs than in papillary RCCs, chromophobe RCCs, and nonneoplastic renal
      tissues. Heparanase was predominantly immunolocalized to cell surface and
      cytoplasm of clear cell RCCs and mean expression levels of heparanase were
      significantly higher in clear cell RCCs than in papillary and chromophobe RCCs.
      The protein expression levels were positively correlated with primary tumor
      stage, distant metastasis, and histologic grade. Targeting of heparanase mRNA
      expression in 786-O and Caki-2 cells with siRNA down-regulated the mRNA
      expression and inhibited the Matrigel invasion by these cells, whereas
      nonsilencing siRNA showed no effect. Multivariate Cox analysis revealed that
      elevated heparanase expression was a significant and an independent predictor of
      disease-specific survival (odds ratio, 8.814; P = 0.019). CONCLUSIONS: These data
      suggest that heparanase plays an important role in invasion and metastasis and
      silencing of the gene might be a potential therapeutic target in clear cell RCCs.

PMID- 18809971
TI  - Selective decrease of bis(monoacylglycero)phosphate content in macrophages by
      high supplementation with docosahexaenoic acid.
AB  - Bis(monoacylglycero)phosphate (BMP) is a unique phospholipid (PL) preferentially
      found in late endosomal membranes, where it forms specialized lipid domains.
      Recently, using cultured macrophages treated with anti-BMP antibody, we showed
      that BMP-rich domains are involved in cholesterol homeostasis. We had previously
      stressed the high propensity of BMP to accumulate docosahexaenoic acid (DHA),
      compared with other PUFAs. Because phosphatidylglycerol (PG) was reported as a
      precursor for BMP synthesis in RAW macrophages, we examined the effects of PG
      supplementation on both FA composition and amount of BMP in this cell line.
      Supplementation with dioleoyl-PG (18:1/18:1-PG) induced BMP accumulation,
      together with an increase of oleate proportion. Supplementation with high
      concentrations of didocosahexaenoyl-PG (22:6/22:6-PG) led to a marked enrichment
      of DHA in BMP, resulting in the formation of diDHA molecular species. However,
      the amount of BMP was selectively decreased. Similar effects were observed after
      supplementation with high concentrations of nonesterified DHA. Addition of
      vitamin E prevented the decrease of BMP and further increased its DHA content.
      Supplementation with 22:6/22:6-PG promoted BMP accumulation with an enhanced
      proportion of 22:6/22:6-BMP. DHA-rich BMP was significantly degraded after cell
      exposure to oxidant conditions, in contrast to oleic acid-rich BMP, which was not
      affected. Using a cell-free system, we showed that 22:6/22:6-BMP is highly
      oxidizable and partially protects cholesterol oxidation, compared with 18:1/18:1
      BMP. Our data suggest that high DHA content in BMP led to specific degradation of
      this PL, possibly through the diDHA molecular species, which is very prone to
      peroxidation and, as such, a potential antioxidant in its immediate vicinity.

PMID- 18809972
TI  - Phosphorylation of eIF4E by MNKs supports protein synthesis, cell cycle
      progression and proliferation in prostate cancer cells.
AB  - Deregulation of the phosphatidyl inositol trisphosphate kinase/AKT/mammalian
      target of rapamycin (mTOR) and RAS/mitogen-activated protein kinase (MAPK)/MNK
      pathways frequently occurs in human prostate carcinomas (PCas) and leads to
      aberrant modulation of messenger RNA (mRNA) translation. We have investigated the
      relative contribution of these pathways to translational regulation and
      proliferation of PCa cells. MNK-dependent phosphorylation of eIF4E is elevated in
      DU145 cells, which have low basal levels of AKT/mTOR activity due to the
      expression of the tumor suppressor PTEN. In contrast, eIF4E phosphorylation is
      low in PC3 and LNCaP cells with mutated PTEN and constitutively active AKT/mTOR
      pathway, but it can be strongly induced through inhibition of mTOR activity by
      rapamycin or serum depletion. Remarkably, we found that inhibition of MNKs
      strongly reduced the polysomal recruitment of terminal oligopyrimidine messenger
      RNAs (TOP mRNAs), which are known targets of mTOR-dependent translational
      control. Pull-down assays of the eIF4F complex indicated that translation
      initiation was differently affected by inhibition of MNKs and mTOR. In addition,
      concomitant treatment with MNK inhibitor and rapamycin exerted additive effects
      on polysomal recruitment of TOP mRNAs and protein synthesis. The MNK inhibitor
      was more effective than rapamycin in blocking proliferation of PTEN-expressing
      cells, whereas combination of the two inhibitors suppressed cell cycle
      progression in both cell lines. Microarray analysis showed that MNK affected
      translation of mRNAs involved in cell cycle progression. Thus, our results
      indicate that a balance between the activity of the AKT/mTOR and the MAPK/MNK
      pathway in PCa cells maintains a defined translational level of specific mRNAs
      required for ribosome biogenesis, cell proliferation and stress response and
      might confer to these cells the ability to overcome negative insults.

PMID- 18809973
TI  - Proteasome inhibition: a new therapeutic option in lupus nephritis?

PMID- 18809974
TI  - Illness trajectories: an important concept in the management of kidney failure.

PMID- 18809975
TI  - Neutrophil gelatinase-associated lipocalin--an emerging troponin for kidney
      injury.

PMID- 18809976
TI  - Ghrelin and other appetite-regulating hormones in paediatric patients with
      chronic renal failure during dialysis and following kidney transplantation.
AB  - BACKGROUND: Patients with renal insufficiency often suffer from cachexia and
      growth retardation due to low appetite and increased resting metabolic rate. The
      neuroendocrine hormone ghrelin, a growth hormone secretagogue, enhances food
      intake, but its role in the development of a cachectic state in renal
      insufficiency is unclear. Objective. The aim of our study was to investigate the
      plasma concentration of total ghrelin and other hormones involved in appetite
      regulation in children with preterminal chronic renal failure (CRF, n = 24),
      children undergoing dialysis (n = 19), children after renal transplantation (RTx,
      n = 59) and healthy controls (n = 10). RESULTS: Total ghrelin was significantly
      elevated in CRF patients (1370 +/- 182 pg/ml; mean +/- SEM) when compared to
      control subjects (682 +/- 106 pg/ml; P = 0.016) or patients following RTx (859 +/
      51 pg/ml; P = 0.002). Furthermore, a negative correlation between glomerular
      filtration rate and total ghrelin was observed in CRF and transplant recipients
      (r = 0.36, P = 0.0006). BMI SDS (standard deviation score) is lower in CRF
      patients compared to the other groups (P < 0.0001). Leptin, adiponectin, blood
      glucose, insulin, IGF-I, IGFBP-3 and growth hormone concentrations did not differ
      among groups. CONCLUSIONS: We observed elevated ghrelin levels in uraemic
      patients despite poor appetite, but the underlying reasons remain unclear. Normal
      ghrelin levels can be re-achieved following RTx.

PMID- 18809977
TI  - Effective removal of protein-bound uraemic solutes by different convective
      strategies: a prospective trial.
AB  - BACKGROUND: Although different on-line convective removal strategies are
      available, there are no studies comparing the efficiency of solute removal for
      the three main options [post-dilution haemodiafiltration (post-HDF), pre-dilution
      haemodiafiltration (pre-HDF) and pre-dilution haemofiltration (pre-HF)] in
      parallel. METHODS: In this study, we compared post-HDF (Polyflux 170), pre-HDF
      (Polyflux 170) and pre-HF (Polyflux 210) in 14 patients. Parallelism of the
      evaluation protocols consisted in applying the same blood flow, dialysis time and
      effective convection (22.9 +/- 1.7 versus 22.2 +/- 2.0 L, P = NS) in pre-HDF
      versus post-HDF, and the same blood flow and dialysis time while comparing pre
      HDF and pre-HF (1:1 dilution). With pre-HF, ultrafiltration was maximized and
      resulted in an effective convective volume of 28.5 L. We studied water-soluble
      compounds (urea, creatinine, uric acid), protein-bound compounds (hippuric acid,
      indole acetic acid, indoxylsulfate and p-cresylsulfate) and beta(2)-microglobulin
      (beta(2)M). RESULTS: Post-HDF was superior to pre-HDF for water-soluble compounds
      and beta(2)M, whereas there was no difference for protein-bound compounds. Pre
      HDF was superior to pre-HF for water-soluble compounds and protein-bound
      compounds. In contrast, removal of beta(2)M for pre-HF was higher than for pre
      HDF, but it did not differ from that obtained with post-HDF. CONCLUSIONS: It is
      concluded that post-dilution is superior to pre-dilution HDF under conditions of
      similar convective volume, and that HDF is superior to HF in pre-dilution, with
      the exception of removal of beta(2)M. Overall, post-HDF is the most efficient
      convective strategy among those tested.

PMID- 18809978
TI  - Copper: two sides of the same coin.

PMID- 18809979
TI  - Strategies for primary and secondary stroke prevention in atrial fibrillation.
AB  - Atrial fibrillation (AF) is the most common type of cardiac rhythm abnormality in
      adults, affecting 1 to 1.5% of the general population in the Western world and is
      the major risk factor for stroke with a fivefold risk compared with the general
      population. Pharmacological and nonpharmacological strategies are available for
      controlling recurrent or permanent AF as well as for prevention of AF. Prevention
      of recurrent AF is one of the best protections against AF-related stroke and
      reduces the prevalence of stroke by almost 25%. Antiplatelet compounds are
      indicated for CHAD scores 0-1 and reduce the risk of stroke from AF by 20 to 25%.
      For CHAD scores >1 oral anticoagulation with vitamin K antagonists is indicated
      and reduces the risk of stroke by 62%. Since inhibitors of coagulation factors
      Xa, VII , or II a have either not been clinically tested for their efficacy for
      prevention of stroke from AF, did not show a comparable effect to well
      established drugs, or had excess side effects (idraparinux, ximelagatran), and
      since mechanical devices are highly questionable concerning their long-term
      effect, there is currently no alternative to oral anticoagulation with vitamin K
      antagonists as primary or secondary stroke prevention in high-risk AF patients.

PMID- 18809980
TI  - Vascular liver disorders (I): diagnosis, treatment and prognosis of Budd-Chiari
      syndrome.
AB  - Budd-Chiari syndrome (BCS) is a venous outflow obstruction of the liver that has
      a dismal outcome if left untreated. Most cases of BCS in the Western world are
      caused by thrombosis of the hepatic veins, sometimes in combination with
      thrombosis of the inferior vena cava. Typical presentation consists of abdominal
      pain, hepatomegaly and ascites, although symptoms may vary significantly.
      Currently, a prothrombotic risk factor, either inherited or acquired, can be
      identified in the majority of patients. Moreover, in many patients with BCS a
      combination of risk factors is present. Myeloproliferative disorders are the most
      frequent underlying cause, occurring in approximately half of the patients.
      Recent discovery of the Janus Kinase 2 (JAK2) mutation has significantly
      contributed to the diagnosis of myeloproliferative disorders. Anticoagulation is
      indicated for all patients with BCS and additional therapy depends on the
      severity of symptoms and the extent of venous obstruction. A stepwise therapeutic
      approach is recommended, with increasing invasiveness and guided by the response
      to previous treatment. A transjugular intrahepatic portosystemic shunt (TIPS) is
      proving to be a good therapeutic option in patients with BCS, diminishing the
      need for surgical shunts. When all other therapy is unsuccessful or in patients
      with fulminant hepatic failure, a liver transplantation should be considered.
      Advances in diagnosis and treatment have dramatically improved the prognosis of
      patients with BCS. Still, many aspects of this complicated disorder remain to be
      clarified.

PMID- 18809981
TI  - Defective interferon-gamma production in patients with hairy cell leukaemia.
AB  - BACKGROUND: Patients with hairy cell leukaemia (HCL) have an increased
      susceptibility to intracellular pathogens, such as mycobacteria and Listeria.
      Although several abnormalities of T-cell populations have been described in HCL,
      the effector mechanism responsible for the increased susceptibility to infections
      is not known. METHODS: Blood was collected from 11 patients with HCL and 22 age-
      and gender-matched volunteers. Proinflammatory cytokine production by freshly
      isolated mononuclear cells was stimulated with either lipopolysaccharide or
      various heat-killed microorganisms. Cytokine concentrations were assessed by
      specific ELISAs. RESULTS: We demonstrate that mononuclear cells harvested from
      HCL patients have a specific defect of IFNgamma production when stimulated with a
      broad panel of bacterial stimuli. In contrast, the production of other
      proinflammatory cytokines, such as TNF, IL-1beta and IL-6, did not differ between
      HCL patients and controls. CONCLUSION: The specific defect in IFNgamma production
      may play a role in the susceptibility of patients with hairy cell leukaemia
      towards intracellular pathogens.

PMID- 18809982
TI  - Haemolytic anaemia as a first sign of Wilson's disease.
AB  - A 19-year-old female presented with haemolytic anaemia and subsequently developed
      liver failure. This raised suspicion of Wilson's disease, which was confirmed by
      Kayser-Fleischer rings, a low ceruloplasmin level, raised 24-hour urinary copper
      excretion and two mutations in the 'Wilson gene'. She was successfully treated
      with D-penicillamine and zinc. In young patients with unexplained haemolysis,
      liver dysfunction or neuro-psychiatric symptoms, Wilson's disease should be
      considered.

PMID- 18809983
TI  - Value of molecular analysis of Wilson's disease in the absence of tissue copper
      deposits: a novel ATP7B mutation in an adult patient.
AB  - Wilson's disease (WD) is a disorder of copper metabolism leading to copper
      accumulation in the liver and in extrahepatic organs, such as brain and cornea.
      We present a patient with liver disease who did not fulfil the biochemical
      criteria for WD. Mutational analysis was necessary to make the diagnosis and show
      a new mutation. Our case supports the use of mutation analysis in cases with
      unclear liver disease and suggests that the spectrum of WD is broader than
      currently assumed.

PMID- 18809984
TI  - Guilty as charged: unmeasured urinary anions in a case of pyroglutamic acidosis.
AB  - A patient developed an unexplained metabolic acidosis with the characteristics of
      renal tubular acidosis. By correcting the serum anion gap for hypoalbuminaemia
      and analysing the urinary anions and cations, the presence of unmeasured anions
      was revealed. The diagnosis of pyroglutamic acidosis, caused by a combination of
      flucloxacillin and acetaminophen, was established. Strategies for solving complex
      cases of metabolic acidosis are discussed.

PMID- 18809985
TI  - 5-Oxoproline as a cause of high anion gap metabolic acidosis: an uncommon cause
      with common risk factors.
AB  - High anion gap metabolic acidosis might be caused by 5-oxoproline (pyroglutamic
      acid). As it is very easy to treat, it might be worth drawing attention to this
      uncommon and probably often overlooked diagnosis. We present three cases of high
      anion gap metabolic acidosis due to 5-oxoproline seen within a period of six
      months.

PMID- 18809986
TI  - Brugada syndrome induced by amitriptyline toxicity.

PMID- 18809988
TI  - A patient with pain in the throat and chest. Spontaneous pneumomediastinum.

PMID- 18809989
TI  - 50 years Netherlands Journal of Medicine.

PMID- 18809990
TI  - Reactivation of dormant microorganisms following a trauma. Pneumonia, sternal
      abscess and calcaneus osteomyelitis due to Mycobacterium tuberculosis.

PMID- 18809991
TI  - Cytogenic abnormalities in buccal cells during spinal deformities in children.
AB  - Evaluation of the incidence of nucleus abnormalities in buccal epithelium allows
      detecting the presence and intensity of the effect of various ecological
      conditions and pathologies of the musculoskeletal system. Two coefficients were
      used: mean number of NA per cell and ratio of cells with karyolysis to the total
      number of cells with NA. Coefficient of karyolysis decreases with increasing
      anthropogenic load In pupils of a special school in Moscow these coefficients
      were similar. Analysis of coefficients showed that karyolysis coefficient was
      reduced in mothers of children with spinal deformities.

PMID- 18809992
TI  - Body mass index of girls in health influences menarche and skeletal maturation: a
      leptin-sympathetic nervous system focus on the trunk with hypothalamic asymmetric
      dysfunction in the pathogenesis of adolescent idiopathic scoliosis?
AB  - Lower body mass index (BMI) and lower circulating leptin levels have been
      reported in girls with AIS. In this paper we evaluate skeletal sizes and
      asymmetries by higher and lower BMI subsets about the means for each of three
      groups of girls age 11-18 years: 1) normals, 2) school screening referrals, and
      3) preoperative girls. Higher and lower BMI subsets, likely to have separated
      subjects with higher from those with lower circulating leptin levels, identify:
      1) girls with relatively earlier and later menarche; 2) trunk width size greater
      in the higher than in the lower BMI subset, of all three groups; 3) abnormal
      upper arm length (UAL) asymmetries (right minus left) in the lower BMI subset of
      the preoperative girls; and 4) in thoracic AIS of screened and preoperative
      girls, Cobb angle and apical vertebral rotation each significantly and positively
      correlate with UAL asymmetry in the lower BMI subset but not in the higher BMI
      subset. In preoperative girls, the lower BMI subset shows the combination of
      relatively reduced pelvic width and abnormal UAL asymmetry, suggesting that both
      are linked to lower circulating leptin levels. An earlier puberty with hormonal
      changes provides a plausible explanation for the larger trunk width at the
      shoulders and pelvis especially at the younger ages in the higher BMI subsets. At
      the shoulders, this widening is driven by the ribcage which, in human evolution
      was acquired with decoupling of head and trunk movements required for efficient
      bipedal gait. The UAL asymmetry patterns within the groups and BMI subsets are
      not explained by hormonal mechanisms. It is hypothesized that 1) normal trunk
      widening of the thoracic cage by hormones in human adolescence is supplemented
      via the sympathetic nervous system under leptin-hypothalamic control influenced
      by energy stores (metabolic fuel); and 2) hypothalamic dysfunction with altered
      hypothalamic sensitivity to leptin through a SNS-driven asymmetric effect may
      create skeletal length asymmetries in upper arms, ribs, ilia and vertebrae, and
      initiate AIS. Additional mechanisms acting in the spine and trunk may be required
      for AIS to progress including 1) somatic nervous system dysfunction, 2)
      biomechanical spinal growth modulation, and 3) osteopenia.

PMID- 18809993
TI  - Volumetric thoracic growth in children with moderate and severe scoliosis
      compared to subjects without spinal deformity.
AB  - Idiopathic scoliosis leads to a three-dimensional thoracic deformity. The purpose
      of this study is to measure thoracic dimensions and volume related to growth and
      to verify the influence of moderate and severe scoliosis. 176 children (36 boys,
      140 girls; 4-16 years) with scoliosis <45 degrees and 17 patients (2 boys, 15
      girls) with scoliosis >65 degrees were compared to 239 children without spinal
      deformity (97 boys, 142 girls) using an optical system. Thoracic volume,
      perimeter, anterior-posterior and transversal diameters, T1-T12 and sternal
      lengths were calculated. These measurements were related to age and sitting
      height. Thoracic volume (3-16 dm(3)) did not differ significantly over growth
      between reference and moderate scoliosis groups. At 4 years, it represents 33%,
      at 10 years it represents 55% of its volume compared with age 16. It triples from
      4-16 years and doubles during puberty. In severe scoliosis, the age related
      thoracic volume was always lower than volumes in reference and moderate scoliosis
      groups. During growth, the transversal diameter corresponds to 30%, the anterior
      posterior diameter represents 20% and the thoracic perimeter 100% of sitting
      height. In severe lordoscoliosis the anterior-posterior diameter represents less
      than 20%. Scoliosis <45 degrees does not influence thoracic volume significantly.
      Severe deformities seem to inhibit volumetric growth. Thoracic parameters should
      be related to growth parameters such as sitting height rather than age because of
      possible height variations in one age section. The established relationships
      offer a reliable orientation of thoracic proportions. They help to understand the
      global deformity and represent a baseline for surgical treatment using vertical
      expandable prosthetic titanium ribs.

PMID- 18809994
TI  - Back trunk morphology in 3301 children aged 3-9 years old.
AB  - The present cross sectional study reveals trunk asymmetry (TA) in "normal"
      Mediterranean juveniles for the first time. The scoliometer readings in both
      standing and sitting forward bending position (FBP) of 3301 children, (1645 boys,
      and 1656 girls) aged from 3 to 9 years old were studied. TA was quantified by
      measuring angle of trunk rotation (ATR) and children were divided in two groups.
      In group I the ATR was 1 degrees to 6 degrees degrees and in group II> or =7
      degrees . 71.25% of boys and 73.27% of girls in standing while 81.13% of boys and
      80.74% of girls in sitting FBP, were symmetric (ATR=0 degrees ). The symmetry
      difference at standing minus sitting FBP for boys and girls was 9.88% and 7.43%
      respectively. Severe asymmetry (ATR> or =7 degrees ) was found in 1.74% of boys
      and in 1.75% of girls at the standing and in 1.21% and 1.22% at the sitting FBP
      respectively. Analysing ATR by age it appears that significant TA changes occur
      between 8-9 years of age for boys and between 6-7 and 8-9 years for girls. The
      amount of trunk asymmetry in children is the indicator for referral and further
      orthopaedic assessment. This report provides, for the first time information
      about the variability of back morphology in "normal" juveniles which is worth
      knowing when a child is examined for juvenile scoliosis.

PMID- 18809995
TI  - The role of the intervertebral disc in correction of scoliotic curves. A
      theoretical model of idiopathic scoliosis pathogenesis.
AB  - Wedging of the scoliotic inter-vertebral disc (IVD) was previously reported as a
      contributory factor for progression of idiopathic scoliotic (IS) curves. The
      present study introduces a theoretical model of IVD's role in IS pathogenesis and
      examines if, by reversing IVD wedging with conservative treatment (full- and
      night-time braces and exercises) or fusionless IS surgery with staples, we can
      correct the deformity of the immature spine. The proposed model implies the role
      of the diurnal variation and the asymmetric water distribution in the scoliotic
      IVD and the subsequent alteration of the mechanical environment of the adjacent
      vertebral growth plates. Modulation of the IVD by applying corrective forces on
      the scoliotic curve restores a close-to-normal force application on the vertebral
      growth plates through the Hueter-Volkmann principle and consequently prevents
      curve progression. The forces are now transmitted evenly to the growth plate and
      increase the rate of proliferation of chondrocytes at the corrected pressure
      side, the concave. Application of appropriately directed forces, ideally opposite
      to the apex of the deformity, likely leads to optimal correction. The wedging of
      the elastic IVD in the immature scoliotic spine could be reversed by application
      of corrective forces on it. Reversal of IVD wedging is thus amended into a
      "corrective", rather than "progressive", factor of the deformity. Through the
      proposed model, treatment of progressive IS with braces, exercises and fusionless
      surgery by anterior stapling could be effective.

PMID- 18809996
TI  - Ultrasound femoral anteversion (FAV) relative to tibial torsion (TT) is abnormal
      after school screening for adolescent idiopathic scoliosis (AIS): evaluation by
      two methods.
AB  - In the scoliotic spine, torsion is generally evaluated in relation to axial
      rotation of the apical vertebra. In the lower limbs, the changes in torsion by
      age of femoral anteversion (FAV) relative to tibial torsion (TT) have been
      studied in dried bones, normal growing subjects and adults and subjects with
      osteoarthritis of the hip or the knee. This paper reports the application of real
      time ultrasound to FAV and TT in normal children age 11-18 years and in scoliosis
      screening referrals with particular reference to how FAV relates to TT as 1)
      ratios, and 2) tibio-femoral index (TFI) of torsion, calculated as TT minus
      femoral FAV. The FAV/TT ratio findings show an abnormal normal relationship of
      FAV to TT both proximo-distally and in left-right asymmetry. These may express
      torsional abnormalities in femoral and/or tibial growth plates with left-right
      asynchrony suggesting the possibility of similar torsional abnormalities in
      vertebral end-plates and/or rib growth plates initiating the deformity of AIS.
      TFI of the right limb in the scoliosis girls is greater than in the normals that
      is interpreted as resulting from earlier skeletal maturation of FAV. FAV/TT
      ratios and TFI are unrelated to the spinal deformity (Cobb angle and apical
      vertebral rotation) except for boys where TFI is associated with apical vertebral
      rotation. FAV/TT ratios may be a more accurate method estimating the relationship
      of FAV to TT. than TFIs.

PMID- 18809997
TI  - Risser sign: the value of the lateral spinal radiograph to assess the excursion
      of the iliac apophysis.
AB  - The course of the ossification of the iliac apophysis is considered in adolescent
      patients with idiopathic scoliosis, under the name of the Risser sign, to
      determine the remaining spinal growth. Although the iliac crest develops in the
      three-dimensional space as a complex structure, the iliac apophysis ossification
      has been assessed only on a one plane frontal spinal radiograph. This study
      points out the usefulness of the lateral radiograph for the visualization of the
      whole iliac crest, especially the posterior region which otherwise cannot be
      observed. Two young female pelvis specimen were examined with anatomical
      measurements and radiography. Lateral spinal radiographs of 201 girls were
      analyzed for the iliac apophysis excursion. The measures of the width of the
      iliac bone beneath the iliac crest revealed one anterior and one posterior thick
      regions, coupled with an intermediate thin region. The regions of the maximal
      thickness corresponded to the earliest appearance of the apophysis ossification
      (Risser 1), while the thin part of the iliac bone corresponded to late appearance
      of the apophysis ossification (Risser 3-4). The ossification of the posterior
      part of the crest was best visualized with the lateral radiograph, which was
      exclusive in showing the posterior superior iliac spine region. On the frontal
      spinal radiograph the end of the course of the apophysis (Risser 3-4) is usually
      searched at the level of the sacroiliac joint, while in reality this point was
      found to be situated more caudal, and accessible for observation on the lateral
      radiograph.

PMID- 18809998
TI  - Stature and growth compensation for spinal curvature.
AB  - Spinal curvatures alter measured stature and may influence the evaluation of
      skeletal maturity and growth based on stature measurements. METHODS: A dataset of
      calibrated measurements of vertebral positions of 407 radiographs in the frontal
      plane, together with clinically measured Cobb angles was used to determine the
      difference between spinal length and spinal height ('height loss') as a function
      of Cobb angles for radiographs indicating both single (N=182) and double (N=225)
      curves. RESULTS: An apparently quadratic relationship: Height loss
      (mm)=1.0+0.066*Cobb+0.0084*Cobb*Cobb was found between height loss and each
      patient's mean Cobb angle for double curves. There was close agreement of the
      regression coefficients for single and double curves, and the present findings
      were very similar to the relationship reported by Ylikoski (Eur Spine J, 2003,
      12:288-291). The relationships differed substantially from those proposed by
      Bjure (Clin Orthop, 1973 93:44-52) and by Brookenthal (SRS Exhibit 15, 2002).
      DISCUSSION AND CONCLUSIONS: The findings of the present study indicate that
      height loss (in mm) occurring with a 10 degrees increase in mean Cobb angle (for
      two curves) would be 1.1+0.16 times the mean Cobb angle (in degrees). For
      example, for a Cobb angle change from 30 to 40 degrees, the expected height loss
      would be 1.1+35*0.16 mm=6.7 mm. This assumes that height loss occurs only as a
      result of altered curvature, without alteration in disc height associated with an
      increase in scoliosis.

PMID- 18809999
TI  - Clinical detectable tension in the growing body: new and revisited signs in
      clinical examination in children with postural problems and spinal deformities.
      Restoration of lordosis on the thoracolumbar junction can correct sagittal and
      coronal plane deformity; a new (revisited) linked approach on the treatment and
      etiology of adolescent spinal deformities.
AB  - Unclear etiology in scoliotic and kyphotic deformities of the spine is
      responsible for uncertainty in treatment options. Normal all-day factors can be
      of importance. Newly developed or revisited clinical examination of sitting and
      supine children and consequent testing of neuro-muscular tightness shows to be
      useful in understanding the different spinal deformations and postural problems
      during growth and point to neuromuscular tension in growth. The goal is: -Better
      understanding of the role and individual characteristics of the central nervous
      system, especially the cord and roots in proper and improper growth of the human
      spine. -Clarifying that preservation of lordosis and good function at the
      thoracolumbar junction at the end of growth can be of value for normal
      configuration and function of the spine in adult life. -Present obvious important
      and consistent clinical observations in children in sitting and supine position
      with early and advanced adolescent deformities, by photographic studies and video
      fragments. Use of work on growth and deformation of the spine by Milan Roth on
      uncoupled neuro-osseous growth and other historical literature. -Relate these
      clinical findings and background literature with common knowledge about
      adolescent spinal deformities and mechanical laws on tensile and compressive
      forces in structures. Overview of relevant clinical tests in the growing child
      presented with deformities show possible correlation with the proposed internal
      balancing problem (uncoupled neuro-osseous growth) researched by Roth.
      Concomitant radiological and MRI signs are shown. Around 1900 most orthopaedic
      surgeons and anatomists saw relationship between the new habitude of children to
      sit for prolonged periods in schools and spinal deformities. A physiological
      explanation as adaptations needed by the total neuromuscular system ("the growing
      system") was widely postulated (Hueter-Volkmann principle) and subject in
      research but a concise theory was not achieved. By recognising positive effects
      of creating lordosis at the thoracolumbar junction of the spine and consistent
      clinical findings in early deformations scientific support was found by earlier
      experimental work of Roth. With a leading role of the central nervous system in
      growth of the spine of standing and sitting vertebrates by steering a tension
      based system, deformation can be understand as adaptations. Consequences for new
      preventive measures and therapeutic strategies in deformities seems possible.

PMID- 18810000
TI  - Quantification of intervertebral efforts during walking: comparison between a
      healthy and a scoliotic subject.
AB  - The accurate quantification of internal efforts in the human body is still a
      challenge in biomechanics. The aim of this study is to quantify the
      intervertebral efforts along the spine during walking, in order to compare the
      dynamical behaviours between a healthy and a scoliotic subject. Practically, one
      healthy subject, one scoliotic patient before an instrumentation surgery (Cobb 41
      degrees ) and after this instrumentation (Cobb 7.5 degrees ) walked on a
      treadmill at 4 km/h. The acquisition system included optokinetic sensors,
      recording the 3D-joint coordinates, a treadmill equipped with strain gauges,
      measuring the external forces independently applied to both feet, and bi-planar
      radiographs, enabling the 3D reconstruction of the spine from C7 to L5, using a
      free form interpolation technique. The intervertebral efforts were computed using
      an inverse dynamical model of the human body in 3D. As results, significant
      differences of the spine kinematics were recorded which lead to different
      internal effort behaviour in magnitude, shift, coordination and pattern when
      normalized to the subject mass. Particularly, the normalized antero-posterior
      intervertebral torques are less uniform for the scoliotic patient (from min -2.5
      to max 1.9 Nm/kg) than the healthy subject (from -1.5 to 1.5 Nm/kg). This
      disequilibrium in the left-right balance of the scoliotic patient is a bit
      rectified after surgery (from -1.3 to 1.1 Nm/kg).

PMID- 18810001
TI  - Measuring the rib hump in scoliosis with ISIS2.
AB  - The three-dimensional shape of the back of 60 patients attending a spinal
      deformity clinic was measured using ISIS2, a non-commercial surface topography
      system using digital photography and structured light. Wire-frame and contour
      plots were displayed, presenting quantitative information and providing a useful
      pictorial representation of the whole back. A numerical parameter representing
      the height of the rib hump was also recorded. Repeat measurements, with the
      patient walking around the room between photographs were carried out. The mean
      difference between the pairs of measurements was -0.08 mm (sd 4.18 mm) and the
      95% tolerance limits were -9.82 mm to 9.66 mm. Changes of greater than +/-10 mm
      are therefore necessary as indicative of clinical change.

PMID- 18810002
TI  - Thoracic kyphosis angle measurements with ISIS2.
AB  - Thoracic kyphosis angle measurements using surface topography with ISIS2 were
      carried out to estimate the inherent variability in the parameter caused by
      natural change in the patient's stance, breathing and muscle tension. A mean
      kyphosis angle of 33.8 degrees (sd 13.4 degrees , range 6 degrees -66 degrees )
      was measured from repeat tests on 61 patients. The mean difference between the
      pairs of measurements was -0.02 degrees (sd 3.18 degrees ) and the 95% tolerance
      limits were -7.41 degrees to 7.38 degrees . This variability is lower than the
      clinically significant change in kyphosis angle reported in the literature. Thus
      kyphosis angle in ISIS2 is suitable for monitoring progress in kyphotic
      deformities.

PMID- 18810003
TI  - Sagittal alignment correction of the thoracolumbar junction in idiopathic
      scoliosis by in situ bending technique.
AB  - A long thoracolumbar sagittal rectitude is sometimes present in adolescent
      idiopathic scoliosis. The purpose of this study was to identify typical patterns,
      by comparing frontal plane deformities and vertebral rotation leading to this
      rectitude. Surgical thoracolumbar alignment correction by three-dimensional in
      situ bending of rods was then analyzed. Pre- and postoperative radiographs of 24
      patients with scoliosis (36-104 degrees) were reviewed using Spineview software.
      Frontal curves and levels of sagittal rectitude were determined. Thoracic
      kyphosis, lumbar lordosis, sacral slope, pelvic incidence, pelvic tilt, T9 and T1
      tilt were measured. Vertebral rotation was measured by computed tomography,
      Perdriolle's, Nash and Moe's methods. The intervertebral mobility of the
      rectitude was analyzed on side bending radiographs. Three patterns leading to
      sagittal rectitude were identified: 11 main thoracic curves (Lenke 1, King 3)
      with cranial prolongation of the physiological thoracolumbar junction (T7T12) and
      maximal vertebral rotation above this zone, 13 double major or thoracolumbar
      curves (Lenke 3 or 5, King 1 or 2) with cranial and caudal prolongation (T9L3)
      and maximal rotation above and below, 1 lumbar curve (Lenke 5) with caudal
      rectitude (T12L4) and maximal rotation at L1. There was no relationship between
      intervertebral mobility and rectitude. Postoperatively, this zone of rectitude
      disappeared in 17 out of 24 patients after anterior release followed by posterior
      instrumentation using the in situ bending technique. In situ bending realizes a
      stepwise correction of the three-dimensional deformity at different levels. An
      accurate preoperative analysis is mandatory to achieve an adequate sagittal
      balance, frontal curve correction and vertebral derotation simultaneously. The
      determined patterns of thoracolumbar rectitude are helpful to plan surgical
      correction accurately.

PMID- 18810004
TI  - A 3-D skeleton model & SEMG approach for integrated neck and low back pain
      analysis test batteries.
AB  - Since several years our group is working on a project to merge into a full 3D
      reliable and detailed human skeleton representation various segmental
      biomechanical models presented in literature. The obtained 3D skeleton model is
      fully parametric and can be fitted to each subject anthropometric
      characteristics. A non-ionising approach based on 3D opto-electronic measurements
      of body landmarks labelled by passive markers has been chosen to build the 3D
      parametric biomechanical skeleton model. A special focus has been devoted to
      identify and model the spine with a correct degree of accuracy and reliability.
      In spine pain related pathologies is of major importance the evaluation of
      functional limitations associated. This requires to integrate morphological
      characteristics with information deriving from other measurements devices as
      force platform data, surface EMG, foot pressure maps. The aim of this study is to
      present a multi-factorial approach which integrates rachis morphological
      characteristics with full skeleton kinematic, dynamic and SEMG measurements to
      quantify spine function and mobility in particular for neck and low back pain. A
      set of clinical-biomechanical tests have been implemented. Static posture
      characteristics are first evaluated. After that, patient is asked to perform
      specific motion test batteries in order to fully measure the whole ROMs (spine
      angles ranges and spine shape modifications) for Axial rotations, forward
      backward flexion-extension, lateral bendings per each spine functional units
      (Skull and neck, thoracic and lumbar districts). During forward bending also a
      digital Schober test is performed. Such data are correlated to simultaneous SEMG
      muscle activities recording to investigate motor co-ordination/dysfunction as
      well as the presence absence of flexion-relaxation phenomena associated to pain.

PMID- 18810005
TI  - Analysis of the mechanisms of idiopathic scoliosis progression using finite
      element simulation.
AB  - The mechanisms of idiopathic scoliosis progression are still not fully
      understood. The aim of this study is to explore, using finite element simulation,
      effect of the combination of gravity and anterior spinal overgrowth on scoliosis
      progression. 14 adolescents (10 girls, 4 boys) with an average age of 10.8 years
      [range 9; 13] were divided in three groups: thoraco-lumbar scoliosis (TL), lumbar
      scoliosis (L), asymptomatic patients (A). Accurate 3D reconstructions of the
      spine have been built using bi-planar X-rays. A patient specific validated finite
      element model has been used. Simulations have been launched with simulation of
      the combined effect of gravity and growth. The progression during the simulation
      was defined by a maximal axial rotation movement greater or equal than 4 degrees
      and a maximal lateral displacement greater or equal than 5 mm ("first order
      progression" for one criterion, "second order" for the both criteria). In the
      group TL, we notice an aggravation for 4 patients (Cobb angle increase at least
      by 4 degrees , mean at 5.9 degrees ). Only three patients of the group L show a
      progression with a smaller Cobb angle increase (mean 3.9 degrees ). For the group
      A, no progression is found for 3 and a progression is found for 1. An anterior
      spinal overgrowth combined with gravity and a pre-existent curve in the spine
      could lead to a progression of scoliosis. It seems necessary to consider
      differently lumbar curves from other curves. Numerical simulation with a patient
      specific model appears as a useful tool to investigate mechanisms of scoliosis
      aggravation.

PMID- 18810006
TI  - The relationship between hip flexion/extension and the sagittal curves of the
      spine.
AB  - The objective of this study was to develop a finite element model (FEM) in order
      to study the relationship between hip flexion/extension and the sagittal curves
      of the spine. A previously developed FEM of the spine, rib cage and pelvis
      personalized to the 3D reconstructed geometry of a patient using biplanar
      radiographs was adapted to include the lower limbs including muscles. Simulations
      were performed to determine: the relationship between hip flexion / extension and
      lumbar lordosis / thoracic kyphosis, the mechanism of transfer between hip
      flexion / extension and pelvic rotation, and the influence that knee bending,
      muscle stiffness, and muscle mass have on the degree to which sagittal spinal
      curves are modified due to lower limb positioning. Preliminary results showed
      that the model was able to accurately reproduce published results for the
      modulation of lumbar lordosis due to hip flexion; which proved to linearly
      decrease 68% at 90 degrees of flexion. Additional simulations showed that the
      hamstrings and gluteal muscles were responsible for the transmission of hip
      flexion to pelvic rotation with the legs straight and flexed respectively, and
      the important influence of knee bending on lordosis modulation during lower limb
      positioning. The knowledge gained through this study is intended to be used to
      improve operative patient positioning.

PMID- 18810007
TI  - Constrained intensity-based image registration: application to aligning human
      back images.
AB  - In this work, an accurate method to register multi-view images of the human torso
      is developed. In particular, a new framework that incorporates prior statistical
      knowledge about the registration is developed and tested. This framework leads to
      a computationally efficient procedure to accurately align images of the human
      torso. An intensity based image registration procedure is used to obtain the
      deformation fields by modelling them as both locally affine and globally smooth.
      Next, the estimated geometric deformation fields are analyzed in order to
      construct a prior deformation model. Two subspace analysis projection techniques
      are used to construct the subspaces of plausible deformations, namely principal
      component analysis (PCA) and independent component analysis (ICA). Accurate
      deformations are now guaranteed by projecting the locally computed geometric
      transformations onto the subspaces of plausible deformations. The proposed
      registration method was validated using high resolution images of the human
      torso. In order to handle the high resolution images, a multi-resolution
      framework was employed in the registration process. Experiments demonstrate
      promising performance in terms of mean square error and in the computational
      complexity. The main contribution of this work is the development of image
      registration method that uses subspace constraints to align images of the human
      torso. This method did not use the intra and inter image constraints used in most
      intensity based image registration algorithms in the literature.

PMID- 18810008
TI  - Ergonomically designed kneeling chairs are they worth it? : Comparison of
      sagittal lumbar curvature in two different seating postures.
AB  - General agreement among researchers suggests that poor seating posture may
      predispose individuals to developing low back pain. A variety of methods such as
      ergonomically designed chairs have been developed to assist people to maintain
      good posture and preserve the 'natural' lumbar curve. The aim of this study was
      to compare lumbar curvature on an ergonomically designed kneeling chair (EKC)
      with that on a standard computer chair (SCC), with reference to the standing
      lumbar curvature. The study used a repeated measures, within-subjects design. A
      convenience sample of twenty participants was recruited aged 18-35 (9 male and 11
      female). Lumbar curvature was measured using the 'Middlesbrough Integrated
      Assessment System' (MIDAS) postural assessment tool in three different postures;
      sitting on a SCC, sitting on an EKC set at +20 degrees inclination and standing
      as the reference measurement. Results were analysed by a repeated measures oneway
      ANOVA (1 factor) with 3 levels followed by the Bonferroni post hoc test. The
      results showed a statistically significant difference between standing lumbar
      curvature and lumbar curvature produced by both of the chairs (p<0.05). There was
      also a statistically significant difference between the two seated positions
      (p<0.05). This study suggests that ergonomically designed kneeling chairs set at
      +20 degrees inclination do maintain standing lumbar curvature to a greater extent
      than sitting on a standard computer chair with an overall mean difference of
      7.633 degrees . Further research with a greater number of subjects and on
      different chair designs is warranted.

PMID- 18810009
TI  - Faulty posture and style of life in young adults.
AB  - Study was aimed to determine the incidence of postural faults, level of physical
      activity and their possible relationship in young adults. Material included 100
      subjects recruited randomly among students of Medical University of Silesia (54F
      aged 20-28, mean=22.9, SD=2.11 and 46M aged 20-29, mean=25.1, SD=1.86). Posture
      was examined according to modified Klapp protocol. For thoracic kyphosis and
      lumbar lordosis, values of 30 degrees +/-2 were considered as normal. ATR
      exceeding 5 degrees was considered as scoliosis. Physical activity was evaluated
      with a questionnaire, admitting 1 point for each hour of physical labour and 2
      points for each hour of sport activity per week. Statistical analysis was based
      on the one-way ANOVA test. Postural faults were widespread in assessed group.
      Most common was lumbar hypolordosis (71.0%, 48.1%F and 97.8%M) and thoracic
      hyperkyphosis (58.0%, 53.7%F and 63.0%M). Scoliosis was observed in 54.0% (50%F
      and 58.7%M). Physical activity in assessed group was high, with 71% of cases
      (76%F and 62.5%M) within range of mean value +/- 1SD. Level of activity in men
      was significantly higher than women (mean 20.25 vs. 6.28 points, p<0.05).
      Significant dependence of postural faults and physical activity was not observed.
      CONCLUSIONS: Young adults prefer active way of life. Postural faults are
      widespread among young adults. Correlation between level of physical activity and
      postural faults was not observed.

PMID- 18810010
TI  - Finite element modeling of vertebral body stapling applied for the correction of
      idiopathic scoliosis: preliminary results.
AB  - Endoscopic vertebral body stapling is an innovative technique intended to treat
      adolescent idiopathic scoliosis, but the optimal instrumentation design is not
      yet established. The objective was to simulate the immediate correction obtained
      from two stapling configurations. A parametric finite element model of a typical
      right thoracic scoliotic spine (Cobb 21 degrees ) was developed using geometrical
      and mechanical data from the literature. Staple insertion and closing were
      modeled. The intra-operative lateral decubitus and standing positions were taken
      into account. Two implant configurations, varying the number of staples per
      vertebra, were simulated. The major correction (9 degrees ) came by simulating
      the intra-operative posture. The immediate Cobb angle correction due to the
      staples alone was less then 1 degrees for both configurations. However, the
      staples helped maintain the correction obtained by the intra-operative posture
      when the post-operative standing position was simulated. Next steps are to
      validate the model using surgical cases, implement growth modulation modeling,
      improve lateral decubitus modeling, and analyze different vertebral stapling
      strategies for different scoliotic curves.

PMID- 18810011
TI  - Influence of correction objectives on the optimal scoliosis instrumentation
      strategy: a preliminary study.
AB  - In three recent studies we have shown how different correction objectives from a
      group of experienced spine surgeons add to the variability in AIS instrumentation
      strategies. This study examined the effect of correction objectives of three
      surgeons on the optimal instrumentation strategy. An optimization method using
      six instrumentation design parameters (e.g. limits of the instrumented segment,
      number, type and location of implants and rod shape) that were manipulated in a
      uniform experimental design framework was linked to a patient-specific
      biomechanical model to analyze the effects of a specific instrumentation
      configuration. The optimization cost function was formulated to maximize
      correction in the three anatomic planes and with minimal number of instrumented
      levels. Three surgeons from the Spinal Deformity Study Group provided their
      respective correction objectives for a single patient (56 degrees thoracic and 38
      degrees lumbar Cobb angle). For each surgeon, 702 surgical configurations were
      iteratively simulated using a biomechanical model. The influence of the three
      different correction objectives on the optimal surgical strategy was evaluated.
      The resulting optimal fusion levels were T2-L4, T4-L2, and T4-L1. A Wilcoxon non
      parametric test analysis showed that fusion levels and the location of implants
      significantly were influenced by the correction objectives strategies (p<0.05).
      The optimal number of implants although different (12 vs.11 vs.10) was not
      statistically significant (p>0.1). Thus different surgeon-specified correction
      objectives produced different optimal instrumentation strategies for the same
      patient.

PMID- 18810012
TI  - Development of an apparatus to evaluate Adolescent Idiopathic Scoliosis by
      dynamic surface topography.
AB  - For cases of Adolescent Idiopathic Scoliosis (AIS), commonly the first indicator
      is a change in the surface shape of the back over time. A proportion of patients
      so diagnosed require surgical intervention to prevent further progression and to
      improve cosmesis. The results of a preliminary literature survey have revealed
      that significant work has already been published on the static acquisition and
      analysis of back surface shape. There is new interest in establishing
      correlations between breathing, posture, the underlying spinal deformity and
      changes in the surface topography of the back during clinical sessions together
      with an increased focus on the impact of the cosmetic defect on the patient and
      in the measurement of pre and post-operative dynamic capability.The continuing
      development of an apparatus based on established optical motion capture
      technologies, that generates a sequence of tri-dimensional images and provides
      measurements derived from changes in the position of anatomical reference
      landmarks and of the surface topography of the back will be presented. If, using
      the same landmarks, the trunk range of motion could be captured concurrently, it
      is hoped that the resulting data would form the basis of a useful clinical study.

PMID- 18810013
TI  - Biomechanical modelling of a direct vertebral translation instrumentation system:
      preliminary results.
AB  - Many new spine instrumentation concepts were introduced in recent years, like the
      incremental direct vertebral translation. The objective was to develop a
      biomechanical model in order to analyze the biomechanics of this instrumentation
      system. The patient-specific spine model was built using the 3D reconstruction
      based on bi-planar radiographs of a scoliotic patient (thoraco-lumbar Cobb: 49
      degrees ). The mechanical properties were derived from literature, experiments on
      cadaver spines and patient's side bending radiographs. Each screw construct was
      modelled by four rigid bodies connected each other by kinematic joints. The screw
      vertebra flexible joint was represented by 3 experimentally derived non-linear
      springs, and the rods by non-linear flexible elements. The correction manoeuvres
      were simulated by lowering the rod, tightening the crimps (incremental segmental
      translation) and applying secondary correction manoeuvres (direct vertebra
      derotation, compression, distraction and construct tightening). The simulations
      showed that the system allows a good force distribution among implants. The long
      post pushing and pulling contributed, to a great extent, to a global correction
      in the coronal plane, while the crimp tightening had more important effect in the
      sagittal plane. The preliminary results illustrated the effectiveness of local
      correction by a direct vertebra translation technique. Our next step is to
      validate the model and compare the performance of this strategy with other spinal
      instrumentation systems.

PMID- 18810014
TI  - SpineCor vs. natural history - explanation of the results obtained using a simple
      biomechanical model.
AB  - In the recent peer reviewed literature the SpineCor is described as an effective
      method of treatment for patients with scoliosis. However until recently no
      prospective controlled end-result study is presented comparing the results
      obtained with this soft brace to natural history. The objective was to determine
      whether the results obtained by the use of the SpineCor are better than natural
      history during pubertal growth spurt. The method employed prospective comparison
      of the survival rates of SpineCor treatment vs. natural history with respect to
      curve progression during pubertal growth spurt. 12 Patients with Cobb angles
      between 16 and 32 degrees (at average 21 degrees) during pubertal growth spurt
      are presented as a case series treated with the SpineCor. Survival rate of this
      sample is described and compared to natural history (SRS brace study 1995). All
      girls treated in both studies were at risk for being progressive with the first
      clinical signs of maturation (Tanner 2-3). During the pubertal growth spurt most
      of the patients (11/12) with SpineCor progressed clinically and radiologically as
      well (at least 5 degrees). Progression could be stopped changing SpineCor to the
      Cheneau brace in most of the sample described (7/10). The avarage Cobb angle at
      the start of treatment with the SpineCor was 21.3 degrees, after an average
      observation time of 21.5 months 31 degrees. At 24 months of treatment time 33% of
      the patients with the SpineCor where still under treatment with their original
      bracing concept, at 72 months follow-up time 8 % of the patients with the
      SpineCor survived with respect to curvature progression. Survival proportion in
      the SpineCor sample, though was 0.08, while in the natural history cohort it was
      0.34. The SpineCor treatment during pubertal growth spurt seems to lead to a
      worse outcome than observation only. The use of a simple biomechanical model
      explains that in the brace the compression forces exceed the lateral forces used
      for the corrective movement. Therefore SpineCor does not seem to be indicated as
      a treatment during pubertal growth spurt.

PMID- 18810015
TI  - Comparison of the kyphosis angle evaluated by video rasterstereography (VRS) with
      x-ray measurements.
AB  - Surface topography evaluations are prone to technical errors due to postural sway
      of the patients measured. The technical error of lateral deviation (rms) and
      surface rotation (rms) may vary between 15 and 20%, while the kyphosis angle (IP
      ITL) has a technical error of only 5% (2,5 degrees), which is comparable to the x
      ray measurement. Purpose of this study was to investigate the hypothesis that
      video rasterstereography can be used for prognostication of a kyphosis patient.
      MATERIALS AND METHODS: 53 Patients (23 females, 30 males, average age 17 years
      with a range from 11 to 56 years) undergoing in-patient rehabilitation have been
      measured with the help of video rasterstereography (VRS) before starting the
      treatment program and the values for kyphosis angle have been correlated to the
      kyphosis angle measured on a lateral x-ray (XR) not older than 6 weeks before VRS
      measurement. 26 had a thoracic Scheuermann, 3 a thoracolumbar, 15 an Idiopathic
      Kyphosis and 9 a kyphosis of other origin. RESULTS: Average Kyphosis angle XR was
      49 degrees (SD 17) and VRS 63 degrees (SD 13). There was a high significant
      Pearson correlation of 0.78 and a high significant difference of 14 degrees in
      the t-test (t -9,6, p<0,001). CONCLUSIONS: The kyphosis angle VRS (Vertebra
      prominens - lower neutral zone of inclination) seems to allow a follow-up of
      individual kyphosis patients. The XR kyphosis angle according to Stagnara is
      measured from T4 to the lower end vertebra and therefore is lower than the VRS
      kyphosis angle measured from T1. The difference found between XR and VRS kyphosis
      angles may be explained by the angle between T1 (VRS) and T4 (XR) differently
      used as the upper end vertebra. Therefore the prognostication of an individual
      patient seems possible within certain limits.

PMID- 18810016
TI  - Postural changes in patients with scoliosis in different postural positions
      revealed by surface topography.
AB  - Claims have been made that surface topography is an objective tool, however there
      are significant postural influences (relatively large technical error due to
      postural sway) those measurements are prone to. Purpose of this study was to help
      estimate these influences by measuring patients with scoliosis in three
      standardized postural positions. MATERIAL AND METHODS: We studied the surface
      topography measurement in 100 in-patients with idiopathic scoliosis divided into
      different age-groups. First group: 7 to 12 years (n=12), second group: 13 to 16
      years (n=51), the third 17 to 20 years (n=15) and the fourth >21 years (n=22) (7
      males and 93 females). The thoracic Cobb angle was 26.4 degrees, lumbar Cobb
      angle 25.7 degrees. We investigated the average lateral deviation (rms) and
      average surface rotation (rms). Measurements were taken one day before the
      patients left the clinic, after a 3 or 4 week in-patient intensive rehabilitation
      program (SIR), in three different postures:Normal posture: no specific
      instructions: standing with feet in an standardized way. Conscious posture: The
      patients acquired this posture during intensive daily exercising. Corrected
      posture: The most corrected posture the patients are able to achieve by using
      specific muscle tension and specific breathing techniques. We compared the
      results between the different postures. Then we calculated the results for the
      different age groups. RESULTS: There are significant differences in both
      parameters tested, some of them more than 40% to 67% greater than the measurement
      error calculated. The best results were achieved in the second and the third
      group with the conscious posture, the adult group had the best valued in most
      corrected posture. For the youngest patients there were no significant changes
      with the different postures. CONCLUSIONS: Surface measurements can be influenced
      by artificial postures and therefore cannot be attributed as objective. This is
      why the surface measurements should be made by someone independent from the
      treatment process in order to exclude any bias as far as possible. Surface
      topography may be used for postural monitoring in the rehabilitation process of
      patients with scoliosis.

PMID- 18810017
TI  - Quantification of localized vertebral deformities using a sparse wavelet-based
      shape model.
AB  - Medical experts often examine hundreds of spine x-ray images to determine
      existence of various pathologies. Common pathologies of interest are anterior
      osteophites, disc space narrowing, and wedging. By careful inspection of the
      outline shapes of the vertebral bodies, experts are able to identify and assess
      vertebral abnormalities with respect to the pathology under investigation. In
      this paper, we present a novel method for quantification of vertebral deformation
      using a sparse shape model. Using wavelets and Independent component analysis
      (ICA), we construct a sparse shape model that benefits from the approximation
      power of wavelets and the capability of ICA to capture higher order statistics in
      wavelet space. The new model is able to capture localized pathology-related shape
      deformations, hence it allows for quantification of vertebral shape variations.
      We investigate the capability of the model to predict localized pathology related
      deformations. Next, using support-vector machines, we demonstrate the diagnostic
      capabilities of the method through the discrimination of anterior osteophites in
      lumbar vertebrae. Experiments were conducted using a set of 150 contours from
      digital x-ray images of lumbar spine. Each vertebra is labeled as normal or
      abnormal. Results reported in this work focus on anterior osteophites as the
      pathology of interest.

PMID- 18810018
TI  - Computer-assisted Cobb angle measurement on posteroanterior radiographs.
AB  - The Cobb angle method is the gold standard to assess severity of scoliosis. A
      computer-aided method was developed to provide a semi-automatic Cobb angle
      measurement during a scoliosis clinic. This study was to evaluate the reliability
      and accuracy of the developed method. Curve types were also tested. The computer
      method required enhancement of the contrast, normalization of the image size, and
      selection of the end-vertebrae on the radiographs before the automatic
      measurement started. The computer-aided process automatically identified the line
      segments that fitted to the endplates of the end-vertebrae. The Cobb angle was
      then calculated from the slopes of these lines. Seventy-six radiographs were
      randomly selected and categorized with Lenke's classification. Among them, 75
      cases were used and categorized into 4 types: 1, 3, 5 and 6. One type 2 case was
      excluded. An orthopedic spine surgeon measured the radiographs manually, serving
      as the reference standard. Two observers used the developed method and measured
      twice. For each curve type, the inter-method, inter-observer, and intra-observer
      variability were analyzed by Intraclass correlation coefficients (ICC[2,1]). The
      ICC values were higher than 0.90 in all these types. The developed method was
      reliable to measure the Cobb angle and was not dependent on the curve type.

PMID- 18810019
TI  - New method of Scoliosis Deformity Assessment: ISIS2 System.
AB  - Scoliosis deformity has been assessed using radiographic angle measurements.
      Surface topography systems are an alternative and complementary methodology.
      Working systems include the original ISIS1 system, Quantec and COMOT techniques.
      Over the last five years the new ISIS2 (Integrated Shape Imaging System) has been
      developed from basic principles to improve the speed, accuracy, reliability and
      ease of use of ISIS1. The aim of this study was to confirm that ISIS2 3D back
      shape measurements are valid for assessment and follow up of patients with
      scoliosis. Three-dimensional back measurements were performed in Oxford. ISIS2
      includes a camera/projector stand, patient stand with a reference plane, and Mac
      computer. Pixel size is approximately 0.5 mm with fringe frequency of
      approximately 0.16 fringes/mm ( approximately 6.5 mm/fringe). Clinical reports in
      pdf format are of coloured images with numerical values. Reports include a height
      map, contour plot, transverse section plots, coronal plot, sagittal sections and
      bilateral asymmetry maps. A total of 520 ISIS2 scans on 242 patients were
      performed from February 2006 to December 2007. There were 58 male patients
      (median age 16 years, SD 3.71, min 7, max 25) and 184 female patients (median age
      14.5 years, SD 3.23, min 5, max 45). Average number of scans per patient was 2.01
      with the range of 1-10 scans. Right sided thoracic curves were the most frequent
      pattern. The median values and 95% CI are reported of back length; pelvic
      rotation; flexion/extension; imbalance; lateral asymmetry; skin angle; kyphosis
      angle; lordosis angle; volumetric asymmetry. ISIS2 scoliosis measurements are non
      invasive, low-cost, three-dimensional topographic back measurements which can be
      confidently used in scoliosis assessment and monitoring of curve progression.

PMID- 18810020
TI  - A novel solution for registration of stereo digital torso images of scoliosis
      patients.
AB  - This paper presents a procedure for registration of a pair of stereo digital
      images giving an improvement in accuracy and speed over existing methods. It does
      so by a novel approach combining color based image segmentation and differential
      geometry. It involves three stages: image segmentation, adaptive local pixel
      matching, and deferential geometry in a tree weighted belief propagation
      procedure. The registration was compared to 2 existing registration procedures,
      segment-based adaptive belief propagation (adaptive BP) and color-weighted
      hierarchical belief propagation (hierarchical BP). A 3D scan of a mannequin was
      obtained and errors in reconstruction were measured for each of the 360 cross
      sections of the mannequin. The proposed procedure outperforms existing methods,
      particularly for high curvature regions and significantly large cross sections.
      Its accuracy of reconstruction ranged from 85-100% compared to 75-100% for other
      existing methods. It was 35% to 40% faster. This work provides a solution to the
      registration problem and is an important step in developing a cost effective
      technique for measuring torso shape and symmetry of scoliosis patients using
      stereo digital cameras.

PMID- 18810021
TI  - Marker placement for movement analysis in scoliotic patients: a critical analysis
      of existing systems.
AB  - Optoelectronic movement analysis systems has provided an opportunity for a
      detailed study of both normal and abnormal human walking and has contributed to
      the planning and documentation of corrective surgical procedures. The majority of
      reported studies have been on the study of lower limbs which, consequently, have
      received most attention in movement analysis. In contrast, movement of the trunk
      and pelvis, important in the identification of spinal mobility and maintaining
      posture, have received limited attention in relation to clinical conditions such
      as scoliosis. Any movement analysis requires the identification of anatomical
      landmarks which are essential contributing factors to the accuracy of the
      analysis. While there are a plethora of studies on marker placements for the
      lower limbs, there is a paucity of information on the marker locations for spinal
      analysis. Present study examines a set of markers previously reported in the
      literature and examines their usefulness in scoliotic gait analysis. The findings
      highlight the drawbacks in previously reported techniques and leads to the
      proposal of a new marker set for spine and back movement analysis.

PMID- 18810022
TI  - The central cord-nervous roots complex and the formation and deformation of the
      spine; the scientific work on systematic body growth by Milan Roth of Brno (1926
      2006).

PMID- 18810023
TI  - Leg-arm length ratios correlate with severity of apical vertebral rotation in
      girls after school screening for adolescent idiopathic scoliosis (AIS): a dynamic
      pathomechanism in the initiation of the deformity?
AB  - There is increasing support for the view that the unique human bipedalism and the
      erect posture are prerequisites for the pathogenesis of adolescent idiopathic
      scoliosis (AIS). How human bipedalism may contribute to the pathogenesis of AIS
      is not clear. In normal humans, axial rotations and counter-rotations of the
      trunk are carried out frequently and forcibly in activities that are not
      performed by quadrupeds. Some workers have analysed gait in AIS subjects, others
      have studied torsions in lower limb bones, but there are only two reports on leg
      arm ratios in relation to AIS. In this paper, leg-arm ratios studied in relation
      to the spinal deformity in scoliosis screening referrals, reveal a highly
      significant correlation with the apical vertebral rotation but not the Cobb angle
      of the scoliosis curves. We suggest that leg-arm proportions and movements during
      gait involving pelvi-spinal axial rotations and thoracic counter-rotations
      contribute a dynamic pathomechanism to early AIS from whatever cause and
      involving the thoracic cage. Curve progression needs other mechanisms that may
      include a central nervous system failure to control structural asymmetry of
      vertebral axial rotation, and biomechanical spinal growth modulation.

PMID- 18810024
TI  - New clinical observations connected with "biomechanical aetiology of so called
      idiopathic scoliosis" (2006-2007).
AB  - Over the last few years, an etiological cause of scoliosis has been developed at
      Lublin, Poland. This is based on the findings of was limited adduction or
      abduction contracture of right hip, coupled to asymmetry of movements between
      right and left hip which influences growth of spine through "asymmetrical gait"
      and asymmetrical standing.

PMID- 18810025
TI  - Etiologic theories of idiopathic scoliosis: autonomic nervous system and the
      leptin-sympathetic nervous system concept for the pathogenesis of adolescent
      idiopathic scoliosis.
AB  - The autonomic nervous system through its hypothalamic neuroendocrine control of
      puberty, skeletal growth and menarche contributes importantly to the pathogenesis
      of adolescent idiopathic scoliosis (AIS). Melatonin dysfunction detected in AIS
      subjects also involves the autonomic nervous system. The thoracospinal concept
      for the pathogenesis of right thoracic AIS in girls thought by some to result
      from dysfunction of the sympathetic nervous system (SNS), is supported by recent
      vascular and peripheral nerve studies. Lower body mass index (BMI).in girls with
      AIS is associated with decreased circulating leptin levels. Leptin, secreted by
      adipocytes, is a master hormone with many regulatory functions for growth and
      reproduction, including: 1) appetite repression, anorexigenic; 2) initiation of
      puberty in girls in a permissive action, and 3) in mice, longitudinal bone
      growth, chondrogenic and angiogenic, and in bone formation, antiosteogenic acting
      centrally through the SNS and possibly directly. In AIS girls, autonomic nervous
      system activity was reported to be higher than in controls. We suggest that in
      AIS susceptible girls, given adequate nutrition and energy stores, circulating
      leptin talks to the hypothalamus where dysfunction leads to an altered
      sensitivity to leptin resulting in increased SNS activity contributing with
      neuroendocrine mechanisms to: 1) earlier age at, and increased peak height
      velocity, 2) general skeletal overgrowth, 3) earlier skeletal maturation, 4)
      extra-spinal skeletal length asymmetries, including periapical ribs and ilia, 5)
      generalized osteopenia, and 6) lower BMI. The SNS-driven effects may also add
      adventitious changes to the spine including asymmetries complicating the
      neuroendocrine effects on adolescent spinal growth. In AIS pathogenesis, the
      leptin-SNS concept is complementary to our NOTOM escalator concept involving the
      somatic nervous system. Together these two concepts view AIS in girls as being
      initiated by a hypothalamic dysfunction of energy metabolism (bioenergetics)
      affecting skeletal growth in the trunk. Where, in susceptible girls, the postural
      mechanisms of the somatic nervous system fail to control the asymmetric spinal
      and/or rib growth changes in a rapidly enlarging adolescent spine; this failure
      becomes evident as mild back-shape shape asymmetry, or scoliosis. The
      environmentally-enhanced stature of normal subjects in the last 300 years, in
      girls susceptible to AIS, may have exaggerated any developmental dysharmony
      between the autonomic and somatic nervous systems being fought out in the spine
      and trunk of the girl - possibly making mild back-shape asymmetry, or scoliosis
      more prevalent today than hitherto.

PMID- 18810026
TI  - Etiologic theories of idiopathic scoliosis. Somatic nervous system and the NOTOM
      escalator concept as one component in the pathogenesis of adolescent idiopathic
      scoliosis.
AB  - There is no generally accepted scientific theory for the causes of adolescent
      idiopathic scoliosis (AIS). In recent years encouraging advances thought to be
      related to the pathogenesis of AIS have been made in several fields. After
      reviewing concepts of AIS pathogenesis we formulated a collective model of
      pathogenesis. The central concept of this collective model is a normal neuro
      osseous timing of maturation (NOTOM) system operating in a child's internal world
      during growth and maturation; this provides a dynamic physiological balance of
      postural equilibrium continuously renewed between two synchronous, polarized
      processes (NOTOM escalator) linked through sensory input and motor output,
      namely: 1) osseous escalator-increasing skeletal size and relative segmental
      mass, and 2) neural escalator - including the CNS body schema. The latter is
      recalibrated continuously as the body adjusts to biomechanical and kinematic
      changes resulting from skeletal enlargement, enabling it to coordinate motor
      actions. We suggest that AIS progression results from abnormality of the neural
      and/or osseous components of these normal escalator in time and/or space - as
      asynchrony and/or asymmetries - which cause a failure of neural systems to
      control asymmetric growth of a rapidly enlarging and moving adolescent spine.
      This putative initiating asymmetric growth in the spine is explained in separate
      papers as resulting from dysfunction of the hypothalamus expressed through the
      sympathetic nervous system (leptin-sympathetic nervous system concept for AIS
      pathogenesis). In girls, the expression of AIS may result from disharmony between
      the somatic and autonomic nervous systems - relative postural maturational delay
      in the somatic nervous system and hypothalamic dysfunction in the autonomic
      nervous system, with the conflict being fought out in the spine and trunk of the
      girl and compounded by biomechanical spinal growth modulation.

PMID- 18810027
TI  - Carrying a rucksack on either shoulder or the back, does it matter? Load induced
      functional scoliosis in "normal" young subjects.
AB  - Approximately 40 million students in the United States and a similar number in
      Europe carry school rucksacks. The average student carries a rucksack weighing
      almost one fourth of his or her body weight. This has led to more than 7,000 A&E,
      referrals each year related to carrying school bags in the US. The purpose of
      this study was to investigate the effects of carrying a rucksack (on each
      shoulder or on both), on 3D spinal curvature in healthy young students. A
      convenience sample of 30 healthy young adults participated in this study. A
      Microscribe 3DX digitiser recorded the three dimensional coordinates of thirteen
      key anatomical landmarks along the spine in four different loading conditions; no
      rucksack (reference) carrying a rucksack (17% body weight) simultaneously on both
      shoulders and solely on the right or the left shoulder. The data obtained was
      analyzed using standard statistical methods. Carrying the load on both shoulders
      resulted in no difference in the frontal plane angle but significantly decreased
      the thoracic kyphosis in the sagittal plane. However, carrying the load on the
      right shoulder significantly increased the thoracic lateral curvature in the
      frontal plane and decreased the thoracic kyphosis in the sagittal plane. This
      study confirms that even carrying a 17% load causes significant changes in spinal
      alignment. It is essential that Health and Safety professionals promote the
      awareness and effects of diverse rucksack carriage modes and excessive rucksack
      weight to avoid the early onset of low back pain.

PMID- 18810028
TI  - Ultrasound femoral anteversion (FAV) and tibial torsion (TT) after school
      screening for adolescent idiopathic scoliosis (AIS).
AB  - Torsion and counter-torsion in the spine are features of the three-dimensional
      deformity of adolescent idiopathic scoliosis, Vertebral axial rotation has
      recently been found in the normal adult thoracic spine. Torsion in the lower
      limbs, femora and tibiae is a feature of normal human skeletal postnatal
      development. In recent years, femoral anteversion (FAV) and tibial torsion (TT)
      have been studied in normal children by imaging techniques, especially
      ultrasound. This paper reports summaries of the application of real-time
      ultrasound to FAV and TT of normal children and scoliosis school screening
      referrals. In the scoliosis girls and boys, the FAV decrease and FAV asymmetry
      compared with normals may result from abnormally increased femoral detorsion
      maturationally earlier with left-right asynchrony which, if repeated as a growth
      plate anomaly in the trunk (spine and/or periapical ribs), might initiate the AIS
      deformity, given other requirements. In scoliosis boys relative to girls, the TT
      decrease without asymmetry may result from sexually dimorphic maturation at knee
      tibial growth plates ? maturationally delayed TT with left-right synchrony.

PMID- 18810029
TI  - Positional relationship between leg rotation and lumbar spine during quiet
      standing.
AB  - Healthcare professionals frequently evaluate spinal posture on visual assessment
      during the clinical examination. While this visual assessment of the spine has
      been shown to be unreliable, the use of a plumbline as to aid clinical visual
      assessment has also been reported. There is a "normal" sagittal contour that
      functions quite well in healthy people. It positions the head in space, it
      protects the neural axis, and it allows efficient, pain-free motion. Lumbar
      lordosis is routinely evaluated in most spine patients, but what constitutes a
      normal sagittal contour is less well defined. A key component of normal sagittal
      contour is lumbar lordosis. Changes in the lumbar lordosis frequently occur in
      pathological gait, usually in association with alterations in pelvic tilt, and
      commonly as a compensation for a limited range of flexion/extension at the hip
      joint. Recent investigations looked at the effect of hyperpronation on pelvic
      alignment in a standing position and supported the existence of a kinematic chain
      in healthy subjects, where hyperpronation can lead to an immediate shank and
      thigh internal rotation and change in pelvic position. While there is a wealth of
      research is available on the effectiveness of functional foot orthoses, the
      present investigation reports the effect of pronated foot position on the lumbar
      region of the back by employing an optoelectronic movement analysis system.

PMID- 18810030
TI  - Aetiology of Idiopathic Scoliosis. What have we learned from school screening?
AB  - The value of school screening as a research tool for Idiopathic Scoliosis (IS)
      aetiology has not been recognized adequately in the literature. The aim of the
      present study is to summarize the contribution of school screening in research of
      IS aetiology. All the relative publications about research of IS aetiology which
      originated from our scoliosis school screening program were analyzed. Information
      is provided about a) the influence of environmental factors in IS prevalence, b)
      the IS prevalence in girls with visual deficiency, c) the role of melatonin in IS
      pathogenesis, d) the age at menarche in IS girls and its relation to laterality
      of the curve, e) the role of the brain in trunk asymmetry and IS pathogenesis, f)
      the role of the thoracic cage in IS pathogenesis, g) the impact of the lateral
      spinal profile, h) the role of the intervertebral discs in IS pathogenesis, i)
      the association of cavus foot with IS and j) anthropometric data in IS patients.
      The present study provides evidence to support that school screening programs
      should be continued not only for early detection of IS or for health care
      purposes, but also as a basis for epidemiological surveys until we learn much
      more about the aetiology of IS.

PMID- 18810031
TI  - Suggestions for improvement of school screening for idiopathic scoliosis.
AB  - There is skepticism and the worth of school screening for the purposes of health
      care has been challenged. Numerous reasons are raised by the negativists to
      abandon these programs, even though the value of school screening is well
      documented in the literature. The aim of the present study is to update the
      evidence based recommendations for the improvement of school screening
      effectiveness, in order to support its continuation. All the relative research
      papers which originated from our scoliosis school screening program were
      analyzed. Specific suggestions for a) the organization, b) the optimal age of
      screening according to the geographical latitude, c) the best examined position,
      d) the standardization of referrals, e) the follow up of younger referrals with
      trunk asymmetry and f) the reduction of the financial cost are made. Today there
      is evidence that the incidence of surgery can significantly be reduced in areas
      where idiopathic scoliosis can be detected at an early stage through these
      programs. The introduction of these recommendations to all the existing school
      screening programs is strongly suggested, to reduce the negative impact they may
      have on families and on the health system and to improve their effectiveness.

PMID- 18810032
TI  - Can future back pain in AIS subjects be predicted during adolescence from the
      severity of the deformity?
AB  - Back pain is frequently reported as a symptom of adolescent idiopathic scoliosis
      (AIS). Prediction of pain in adulthood would be useful to identify subjects
      requiring follow-up. The aim is to determine adolescent predictors of adult back
      pain. This study is a retrospective review of 27 females with AIS who attended
      our pediatric scoliosis clinic and later completed the SRS-22 questionnaire as
      young adults (range 18-25 years). Subjects with surgery at baseline (age 14-16
      years) were excluded. The relationships between largest curve size,
      decompensation and trunk twist at baseline and pain as measured by the SRS-22
      pain domain as young adults were studied. At baseline, subjects had a largest
      curve of 47+/-15 degrees , decompensation of 18+/-14 mm and trunk twist of 14+/-6
      degrees . At follow-up, 5.3+/-1.9 years later, the total SRS-22 score was 3.9+/
      0.3 and the pain domain score was 3.9+/-0.7. Pearson correlations between the SRS
      22 pain domain and largest curve, decompensation and trunk twist were 0.17, -0.11
      and -0.25, respectively (p>0.05). Individual questions within the pain domain had
      similar correlations. Even though the sample represented a wide range of
      scoliosis severity at baseline and a wide range of pain scores (2.4 to 5) at
      follow-up, baseline scoliosis deformity parameters of largest curve size,
      decompensation and trunk twist did not predict scoliosis-related pain in young
      adulthood.

PMID- 18810033
TI  - A machine learning approach to assess changes in scoliosis.
AB  - This paper presents a machine learning approach that can be used to evaluate the
      validity of the results obtained with an automated system to measure changes in
      scoliotic curves. The automated system was used to measure the inclinations of
      141 vertebral endplates in spine radiographs of patients with scoliosis. The
      resulting dataset was divided into training and test set. The training set was
      used to configure three classifiers: a support vector classifier (SVC), a
      decision tree classifier (DT) and a logistic regression classifier (LR). Their
      performance was evaluated on the test set. The SVC had an accuracy of 86%
      discriminating Good Results (those in which the error was less than 3 degrees )
      from Bad Results. This accuracy was better than that of the LR (76%) and DT
      (68%). The differentiation between Good and Bad Results using the proposed
      machine learning approach was achieved successfully.

PMID- 18810034
TI  - The posterior skeletal thorax: rib-vertebral angle and axial vertebral rotation
      asymmetries in adolescent idiopathic scoliosis.
AB  - The deformity of the ribcage in thoracic adolescent idiopathic scoliosis (AIS) is
      viewed by most as being secondary to the spinal deformity, though a few consider
      it primary or involved in curve aggravation. Those who consider it primary
      ascribe pathogenetic significance to rib-vertebra angle asymmetry. In thoracic
      AIS, supra-apical rib-vertebra angle differences (RVADs) are reported to be
      associated with the severity of the Cobb angle. In this paper we attempt to
      evaluate rib and spinal pathomechanisms in thoracic and thnoracolumbar AIS using
      spinal radiographs and real-time ultrasound. On the radiographs by costo
      vertebral angle asymmetries (rib-vertebral angle differences RVADs, and rib
      spinal angle differences RSADs), apical vertebral rotation (AV) and apical
      vertebral translation (AVT) were measured; and by ultrasound, spine-rib rotation
      differences (SRRDs) were estimated. RVADs are largest at two and three vertebral
      levels above the apex where they correlate significantly and positively with Cobb
      angle and AVT but not AVR. In right thoracic AIS, the cause(s) of the RVA
      asymmetries is unknown: it may result from trunk muscle imbalance, or from ribs
      adjusting passively within the constraint of the fourth column of the spine to
      increasing spinal curvature from whatever cause. Several possible mechanisms may
      drive axial vertebral rotation including, biplanar spinal asymmetry, relative
      anterior spinal overgrowth, dorsal shear forces in the presence of normal
      vertebral axial rotation, asymmetry of rib linear growth, trunk muscle imbalance
      causing rib-vertebra angle asymmetry weakening the spinal rotation-defending
      system of bipedal gait, and CNS mechanisms.

PMID- 18810035
TI  - Prediction of the T2-T12 kyphosis in adolescent idiopathic scoliosis using a
      multivariate regression model.
AB  - The paper presents a nonlinear regression model built on the coronal thoracic
      curvature, the lumbar lordosis and the slope of the first lumbar vertebra in
      order to estimate the thoracic kyphosis measure between T2 and T12. To train the
      proposed model, a large database containing scoliotic spines demonstrating
      several types of scoliotic deformities was used to train the proposed system by a
      cross-validation method. Validation was performed on patients exhibiting three
      different types of sagittal thoracic profiles: normal, hypo-kyphotic, and hyper
      kyphotic. Results show that a multivariate regression model based on dependent
      variables is able to predict with a reasonable accuracy the sagittal thoracic
      kyphosis for the automatic assessment and classification of the spinal curve.

PMID- 18810036
TI  - Intervertebral disc changes in an animal model representing altered mechanics in
      scoliosis.
AB  - The intervertebral discs become wedged and narrowed in a scoliosis curve, and
      this may be due in part to altered biomechanical environment. To study this,
      external rings were attached by percutaneous pins transfixing adjacent vertebrae
      in 5-week-old Sprague-Dawley rats and four permutations of mechanical conditions
      (4 groups of animals) were compared: (A) 15 degrees Angulation, (B) Angulation
      with 0.1 MPa Compression, (C) 0.1 MPa Compression, and (D) Reduced mobility.
      These altered mechanical conditions were applied for 5 weeks. After 5 weeks, disc
      narrowing at the intervention levels was evident in micro-CT images. Average disc
      space loss as a percent of the initial values over the 5 weeks was 19%, 28%, 22%
      and 20% four groups listed above. Increased lateral bending stiffness relative to
      within-animal controls was also observed at all groups. The minimum stiffness was
      recorded at an angle close to the in vivo value, indicating that angulated discs
      had adapted to the imposed deformity. In the angulated and compressed discs there
      was a small difference in the amount of collagen crimping in the disc annuli
      between concave and convex sides. All experimental interventions produced
      substantial changes in the intervertebral discs of these growing animals.
      'Reduced mobility' was present in all interventions, and the changes in the discs
      with reduced mobility alone were comparable with those in loaded and angulated
      discs. This suggests that imposed reduced mobility is the major source of disc
      changes, and may be a factor in disc degeneration in scoliosis. Further studies
      are in progress to characterize gene expression, matrix protein synthesis and
      composition in these discs.

PMID- 18810037
TI  - Knowledge about idiopathic scoliosis among students of physiotherapy.
AB  - The aim of the study was to determine the level of basic knowledge about
      idiopathic scoliosis (IS) among students of physiotherapy. The study included 37
      students of Medical University of Silesia (17F and 20M aged 22-25, mean 22.6),
      attending the 3(rd) year of a 1(st) degree of physiotherapy. All students had
      credits in kinesiotherapy, including methods of conservative treatment of IS.
      Students were examined using a questionnaire, comprising general knowledge of IS,
      questions related to sagittal plane correction, influence of various physical
      activities on IS and known methods of conservative treatment. 81 students
      considered IS as 3-D deformity. 62.2% of those questioned would diagnose IS when
      the Cobb angle reaches 10 degrees . All students agreed that the aetiology of IS
      remains unknown. 54.1% considered forcible extensory exercises of back as
      favourable in IS. Questioned students mostly preferred swimming (94.6%), yoga
      (73.0%) and martial arts (32.4%) as beneficial to IS. The methods of conservative
      treatment which were known best were: Lehnert-Schroth-Weiss (94.6%), Klapp
      (91.9%), Majoch (89.2%) and Dobosiewicz (78.4%). The conclusions indicate that
      the average level of knowledge of idiopathic scoliosis among students of
      physiotherapy is unsatisfactory, despite the education programme including the
      SOSORT guidelines. Education in the field of scoliosis should be comprehensive
      and meet contemporary guidelines and standards.

PMID- 18810038
TI  - Thoracoplasty in the surgical treatment of adolescent idiopathic scoliosis.
AB  - A consecutive series of 40 adolescents surgically treated between 1998-2001, by
      posterior spinal fusion and thoracoplasty were compared with a similar group of
      40 adolescents treated in the same period by posterior only segmental fusion.
      Clinical and radiographic analysis was performed, including the SRS-30
      questionnaire and Pulmonary Function Tests (PFT). Minimum five years follow-up
      was requested. No statistical differences were found between the two groups in
      PFT's both pre-operatively and at latest follow up. Our findings suggest that
      thoracoplasty did not adversely affected long-term PFT's in AIS patients treated
      by posterior spinal fusion alone.

PMID- 18810039
TI  - Preliminary validation of curve progression model for brace treatment.
AB  - Brace treatment is the most commonly used non-surgical treatment for adolescent
      idiopathic scoliosis (AIS). A brace compliance monitoring system consisting of a
      microcomputer and a force transducer was used to monitor how brace candidates
      used their braces during daily activates. A prediction model of the brace
      treatment outcome was developed based on 20 AIS subjects. Six subjects (1M, 5F)
      with AIS who had worn their braces for six weeks participated into this study.
      One month data was recorded during the study period. Knowing the risk progression
      at the beginning of brace treatment plus how brace subjects used their braces in
      terms of brace tightness and wear time during brace treatment yielded a predicted
      outcome which was compared to the final treatment outcomes with 2 years followed
      up. This preliminary result demonstrated that the prediction model was able to
      predict the treatment outcome within +/-3.5 degrees.

PMID- 18810040
TI  - BRACE MAP, a proposal for a new classification of braces.
AB  - Braces today are named according to the author's name or town. The existing
      classification of braces considers only the anatomical spinal section involved
      (C: cervical; T: thoracic; L: lumbar; S: sacral; Orthosis). The absence of a more
      detailed classification do not allow to really distinguish between the different
      braces and to have a common language between the conservative treatment experts.
      Our aim was to propose and verify a new classification of braces. We developed
      the classification and applied it to 13 different braces (Boston, Charleston,
      Cheneau 2000, Lapadula, Lyonese, Maguelone, Milwaukee, PASB, Providence,
      Sforzesco, Sibilla, SpineCor, Triac). We considered the following items (acronym
      BRACE MAP): Building, Rigidity, Anatomical classification, Construction of the
      Envelope, Mechanism of Action, Plane of action. Each item is composed by 2 to 7
      classificatory elements defined using one or maximum two letters, so that from
      the classification it is possible to come back to the brace characteristics. Out
      of the 13 braces considered, BRACE MAP did not allow to differentiate only two.
      This first proposal needs to be refined through Consensus and discussions that
      are already underway in the international Society On Scoliosis Orthopaedic and
      Rehabilitation Treatment (SOSORT); nevertheless, BRACE MAP appears to be useful
      in distinguishing between the existing braces.

PMID- 18810041
TI  - Clinical and postural behaviour of scoliosis during daily brace weaning hours.
AB  - What happens to scoliosis when the brace is daily weaned is not described in the
      literature, even if this can have a significant clinical impact. Our aim was to
      evaluate the postural and clinical changes at brace weaning. We developed a pre
      post trial in 10 adolescent idiopathic scoliosis female patients 12.6 years old,
      with 42.8+/-7.4 degrees Cobb curves. INCLUSION CRITERIA: more than 30 degrees
      Cobb; TLSO worn at least 20 hours/day. Patients have been divided according to
      the hours of brace wearing per day: group 23H (6 patients, 23 hours per day) and
      group 20H (20-21 hours per day). We evaluated the patients at brace weaning and
      every hour per 4 hours, clinically (Bunnell degrees, hump and plumbline distances
      through usual clinical instruments) and posturally (scoliosis degree), by means
      of a non-ionising instrument that allow a 3D reconstruction of the spine. Paired
      ANOVA and t-test were used for statistical analysis. Group 23H showed
      statistically significant variations in 1 to 3 hours in all clinical parameters,
      and a tendency to progression of scoliosis. Group 20H did not show any
      statistically significant variation in 4 hours, a part from slight improvements.
      These results could be explained in terms of scoliosis reactions to usual/unusual
      daily load on the spine. Moreover, these data show the possible existence of the
      "concertina effect" due to brace weaning, and the importance of standardizing
      clinical examination with respect to the daily brace weaning hours.

PMID- 18810042
TI  - Do imbalance situations stimulate a spinal straightening reflex in patient with
      adolescent idiopathic scoliosis?
AB  - Correlation between balance and Adolescent Idiopathic Scoliosis (AIS) is still
      unclear. To identify the most useful type of physical exercises to be proposed
      for conservative treatment, is interesting to explore better this field. Our aim
      was to evaluate the changes of scoliosis curves in a group AIS patients while
      submitted to an unbalancing situation. We considered in a pre-post trial 14 AIS
      patients (46 curves), 12 to 15 years old, with 19.3+/-9.9 degrees Cobb curves.
      Assessment has been made using GOALS (Global Optoelectronic Approach for
      Locomotion and Spine), a non-ionising instrument that allow a 3D reconstruction
      of the spine. We evaluated the patients twice in a standardised standing
      position: on the floor, and on a sway bench. On the sway bench there was a
      statistically (but not clinically) significant reduction of the curves. This was
      confirmed considering the average of the curves of each patient, but not when
      considering the worst curve. Looking at the curves, 13% worsened and 33%
      improved, versus 14% and 43% respectively looking at the patients. We did not
      find similar reactions in all patients, but in general a spinal straightening
      reflex while on a sway bench appears. In any case these variations are of low
      degree.

PMID- 18810043
TI  - Congenital scoliosis - presentation of three severe cases treated conservatively.
AB  - In view of the very limited data about conservative treatment of patients with
      congenital scoliosis (CS) available, early surgery is suggested already in mild
      cases with formation failures in the first three years of life. It is common
      sense that patients with failures of segmentation will not benefit from
      conservative treatment at all and the same applies to failures of formation with
      curves of >50 degrees in infancy. MATERIALS AND METHODS: Two patients with rib
      synostosis denied surgery before entering the pubertal growth spurt. These
      patients have been treated conservatively with braces and Scoliosis In-Patient
      Rehabilitation (SIR) and now are beyond the pubertal growth spurt. One patient
      with a formation failure and a curve of >50 degrees lumbar has been treated with
      the help of braces and physiotherapy from 1.6 years on and is still under
      treatment now at the age of 15 years. RESULTS: Severe decompensation was
      prevented in the two patients with failure of segmentation, however a severe
      thoracic deformity is evident with underdeveloped lung function and severe
      restrictive ventilation disorder. The patient with failure of formation is well
      developed, now without cosmetic or physical complaints although his curve
      progressed at the end of the growth spurt due to final mal-compliance.
      CONCLUSIONS: Failures of segmentation should be advised to have surgery before
      entering the pubertal growth spurt. In case they deny, conservative treatment can
      at least in part be beneficial. For patients with failures of formation
      conservative treatment should be suggested in the first place because long-term
      outcomes of early surgery beyond pubertal growth spurt are not yet revealed.

PMID- 18810044
TI  - Conservative scoliosis treatment in patients with Prader-Willi syndrome.
AB  - Patients with Prader-Willi syndrome often suffer from scoliosis of major degrees.
      Due to current literature surgical intervention seems the gold standard of
      treatment although the rate of complications in this condition are reported to be
      significantly higher than in patients with Adolescent Idiopathic Scoliosis.
      Purpose of this study was to reveal the effects of conservative treatment in this
      rare patient population. MATERIALS AND METHODS: A case series of patients with
      this condition has been investigated to estimate as to whether Prader-Willi
      patients with scoliosis may benefit from conservative scoliosis management. 9
      Patients with this condition have been found in our out-patient database. 5 of
      these retarded patients (3 girls, two boys) today are 19 years and older and
      therefore are without any significant residual growth. Average Cobb angle was 47
      degrees (34 - 66 degrees) at 12 years, average observation time was 6.4 years.
      RESULTS: Two of the five patients progressed. Average Cobb angle after follow-up
      was 52 degrees. No progression beyond 70 degrees has been found after cessation
      of growth. In one patient the curve deteriorated clearly after reducing brace
      wearing time and therefore was due to non-compliance. CONCLUSIONS: Stabilisation
      of scoliosis due to Prader-Willi syndrome is possible by means of conservative
      management. To expose this patient population to the risks of surgical management
      seems not to be justified.

PMID- 18810100
TI  - Phonophoresis: the principles of the ultrasonic driving force and efficacy in
      treatment of common orthopaedic diagnoses.
AB  - Phonophoresis with antiinflammatories or local anaesthetics is utilized by
      physical therapists as part of their treatment plans. The physics of ultrasound
      and the mechanical, thermal, chemical, biological, and physiological effects on
      the body's tissues are reviewed. Experimental studies cited showed increased
      muscle and nerve cortisol concentration when a topical application is followed by
      ultrasound. Clinical studies demonstrate greater pain relief and functional range
      of motion improvement when treatment protocols opted for hydrocortisone
      phonophoresis as opposed to ultrasound. Phonophoresis is compared to
      iontophoresis as another means of driving a topically applied medication into the
      tissues, and the benefits of each are discussed. J Orthop Sports Phys Ther
      1982;4(2):99-102.

PMID- 18810101
TI  - Case study: compression fracture of thoracic spine with emphasis on fabrication
      of a protective pad for athletic participation.
AB  - Preparation for return to full competition by an injured athlete can be enhanced
      by the use of a protective pad. This article presents the fabrication of a
      protective pad for a compression fracture of TI, with resulting prominence of the
      spinous process. The mechanism of injury of a compression fracture for the
      thoracic vertebrae is discussed and general guidelines for the proper
      construction of a pad are presented. J Orthop Sports Phys Ther 1982;4(2):115-117.

PMID- 18810102
TI  - Rolling to a lift.
AB  - A dynamic method to kneel and return to standing has been suggested. An
      amalgamation of principles and experiences has encouraged the advent of rolling
      to a lift. The method is applicable for patients with at least fair trunk
      control. J Orthop Sports Phys Ther 1982;4(2):118-119.

PMID- 18810103
TI  - A Case Report: Lithium lontophoresis for Gouty Arthritis.
AB  - Pain and swelling associated with gouty arthritis are treated successfully with
      lithium iontophoresis. tonic exchange between lithium and sodium favorably
      affects solubility of urates formed, and is believed to have a sclerolytic effect
      upon tophi, if present.J Orthop Sports Phys Ther 1982;4(2):113-114.

PMID- 18810104
TI  - Electrical stimulation as a strength improvement technique: a review.
AB  - The dominant philosophy within rehabilitation has been that electrical
      stimulation is a valuable kinesthetic muscle reeducation technique, but voluntary
      exercise is of greater benefit in restoring voluntary muscular control and
      improving the strength of injured muscle. Much publicized Soviet research has
      suggested that this preference for voluntary exercise may be inappropriate and
      that electrical stimulation is the technique of choice for strengthening normally
      innervated muscle. This position has not been supported by the limited non-Soviet
      research. Whether this lack of support is attributable to an inability to
      duplicate the Soviet current format and/or application technique, or simply that
      electrical stimulation programs are not more effective than voluntary exercise
      programs, is presently unknown. To date, neither the voluntary exercise
      philosophy nor the nonvoluntary exercise (electrical stimulation) philosophy has
      overwhelming scientific support. Electrical stimulation programs must be compared
      with traditional voluntary exercise programs before practitioners are in a
      position to confidently accept or to refute either method. Until an adequate
      number of research studies have been conducted, practitioners cannot meet their
      obligation to know what the most effective strength improvement techniques are
      and to make such treatment available.J Orthop Sports Phys Ther 1982;4(2):91-98.

PMID- 18810105
TI  - The Effects of Submaximal Contractions on an lsokinetic Test Session.
AB  - The purpose of this study was to examine changes in peak torque and to determine
      if an isokinetic measure of maximal knee extensor strength changed significantly
      in the presence or absence of submaximal isokinetic contractions. Twenty subjects
      were randomly divided into two groups. Group 1 performed three gradient
      submaximal isokinetic contractions prior to the test session, and group 2 did not
      perform submaximal contractions. The test session consisted of six trials with
      each trial consisting of a maximal isokinetic contraction at 30 degrees /second.
      No significant differences were found among trials, between groups, and within
      each group. A trend analysis of each group revealed a significant positive linear
      trend (P < 0.05) in group 1 with no significant trend in group 2. Subjective data
      demonstrated that the three gradient submaximal contractions were adequate to
      prevent discomfort during the following test session.J Orthop Sports Phys Ther
      1982;4(2):74-77.

PMID- 18810106
TI  - Assessment of selected reports on the strength relationship of the knee
      musculature*.
AB  - Fifty reports (1 956- 1981) pertaining to the measurement of knee flexor and
      extensor muscle strength were reviewed. The purpose of the literature review was
      to identify and evaluate the major variables which prevent a direct comparison of
      results obtained using isometric, isotonic, and isokinetic testing devices.
      Biomechanical factors were discussed relative to each type of device and included
      the length-tension relationships, angle of pull, and speed of contraction.
      Differences in the procedures used to acquire strength data were also reviewed.
      The conclusion was that the strength relationship between the knee flexor and
      extensor muscle groups was not adequately described by one or even a small range
      of strength values, and that there was no fixed strength relationship between
      these muscle groups that could be appropriate for every person and under all
      circumstances. This view was contrary to the generally accepted guideline for
      sports participants that the knee flexor muscle group should generate at least
      60% of the force produced by the ipsilateral knee extensor muscle group.J Orthop
      Sports Phys Ther 1982;4(2):78.85.

PMID- 18810107
TI  - Effectiveness of foot orthotic devices used to modify pronation in runners*.
AB  - Foot orthotic devices (FOD) are often used to treat excessive pronation and
      related problems of runners. In order to assess the effectiveness of FOD, 29
      runners who used FOD were filmed on an outdoor track during three conditions: 1 )
      barefoot, 2) running shoe, and 3) running shoe plus FOD. The barefoot data were
      not used because of marked variability. Comparison between the shoe and FOD
      conditions showed that only two of the six variables were statistically
      significant at the 0.05 level. Both the maximum angle of pronation and percentage
      of support time in pronation on the left foot were significantly decreased in the
      FOD trial. No significant differences were found between the shoe and FOD
      conditions for the other four variables (pronation velocity on both feet, maximum
      angle of pronation on the right foot, and percentage of support time spent in
      pronation on the right foot). The variability of these results support the
      conclusion that the type of FOD used in this study have questionable
      effectiveness in the treatment of excessive pronation. J Orthop Sports Phys Ther
      1982;4(2):86-90.

PMID- 18810108
TI  - Introduction of Antiinflammatory Drugs by lontophoresis: Double Blind Study.
AB  - A double blind study was performed on 53 patients in introducing anti
      inflammatory drugs by iontophoresis. The objective was to see if local
      iontophoretic administration of an antiinflammatory drug to patients with
      tendonitis at the shoulder joint would achieve results similar to those obtained
      by local injection of the drug. Patients below the age of 45 years with shoulder
      dysfunction related to primary tendonitis responded to iontophoresis steroid
      administration. Patients in the age group above 45 years with a primary diagnosis
      of cervical degenerative change demonstrated less pain relief in shoulder
      tendonitis whether the steroids were administered by local injection or by
      iontophoresis. J Orthop Sports Phys Ther 1982;4(2):103-108.

PMID- 18810109
TI  - lontophoresis: Clinical Research in Musculoskeletal lnf lammatory Conditions.
AB  - Fifty patients with various musculoskeletal inflammatory conditions were treated
      with iontophoresis (direct current 5 milliamperes, 20 minutes). The treatment
      drugs were 1 cubic centimeter, 4 milligrams per milliliter of dexamethasone
      sodium phosphate (Decadron) combined with 2 cubic centimeters of 4% Xylocaine.
      Thirty-eight of the 50 patients had an excellent relief of pain and symptoms,
      seven reported moderate relief, and five patients had little or no change. There
      were no significant side effects. It was concluded that iontophoresis is an
      effective mode of delivering ionized antiinflammatory drugs to inflamed tissues.
      It is effective, painless, and safe, and provides a viable treatment. J Orthop
      Sports Phys Ther 1982;4(2):109-112.

PMID- 18810110
TI  - Cyriax's Friction Massage: A Review.
AB  - This article reviews the existing literature on connective tissue in an attempt
      to provide additional substantiation for the use of Dr. James Cyriax's friction
      massage. J Orthop Sports Phys Ther 1982;4(1):16-22.

PMID- 18810111
TI  - Segmental Instability of the Lumbar spine and its Management.
AB  - This case study is presented to describe and illustrate segmental instability, a
      mechanical disorder of the lumbar spine that may mimic a ruptured disc with nerve
      root entrapment. The differential diagnosis may be made through physical
      examination and roentgenographic assessment. Treatment includes a specific
      exercise program, weight reduction in obese patients, and possible use of a
      flexion brace. J Orthop Sports Phys Ther 1982;4(1):3-5.

PMID- 18810112
TI  - Pressure changes in the carpal tunnel with movement of the pisiform bone.
AB  - Seven fresh cadaveric forearms were studied to investigate the effects of medial
      and lateral positioning of the pisiform bone on pressure within the carpal
      tunnel. The wick catheter, a device used to transmit interstitial fluid pressure,
      was inserted into the carpal tunnels of the cadavers. Pressures in the tunnel
      with the pisiform in a resting position, medial position, and lateral position
      were measured via a water manometer. A significant increase in pressure was noted
      between the resting position and both the medial and lateral positions ( p =
      0.001). No significant difference was found between the medial and lateral
      positions ( p > 0.05). Findings suggest that the use of movement of the pisiform
      as a conservative treatment in carpal tunnel syndrome is questionable. J Orthop
      Sports Phys Ther 1982;4(1):47-50.

PMID- 18810113
TI  - Calculation of lsokinetic Rehabilitation Velocities for the Knee Extensors.
AB  - The aim of this study was to evaluate the validity of a method which provides for
      the calculation of the isokinetic speed of knee rehabilitation. The results
      indicated that, for the sampled population, the method produced validity
      coefficients (r = 0.98; r = 0.94) in the excellent range. Therefore, it was
      concluded that the utilization of this method may be appropriate in knee cases
      where the torque transmitting capacity of the capsule, ligaments, and tendons are
      in question. J Orthop Sports Phys Ther 1982;4(1):32-35.

PMID- 18810114
TI  - Implementation of an On-Line lsokinetic Analysis System.
AB  - A cost effective and efficient means of obtaining torque, work, and power
      measurements for a large group of subjects was needed. As a solution to this
      problem, an Apple 111 microcomputer was interfaced to a Cybex II isokinetic
      dynamometer. This system provided instantaneous values for the three parameters
      listed above as well as additional options for filekeeping and data manipulation.
      Intraclass reliability coefficients for the parameters of torque, work, and power
      ranged from r = 0.991 to r = 0.999. It was concluded that a microcomputer support
      system is, in view of its time saving qualities and relative cost, an economical
      and efficient means of providing meaningful information for clinical analysis of
      patients. J Orthop Sports Phys Ther 1982;4(1):36-38.

PMID- 18810115
TI  - A comparative study of three methods of treatment for shoulder girdle myofascial
      syndrome.
AB  - In order to determine the most effective method of treatment for a work-induced
      shoulder problem diagnosed as shoulder girdle myofascial syndrome, a comparative
      study of three different treatment procedures was conducted. The treatment
      procedures were as follows: 1) treatment with muscle relaxant and analgesic
      medication; 2) treatment with hydrocollator/ultrasound modalities; and 3)
      treatment with medication administered by iontophoresis. Results of the study
      indicated iontophoresis to be the most effective treatment. J Orthop Sports Phys
      Ther 1982;4(1):51-54.

PMID- 18810116
TI  - Controlling Anterior Shear During lsokinetic Knee Extension Exercise.
AB  - The purpose of this paper is to present a means of controlling anterior shear
      force at the knee during isokinetic exercise. A dual-pad attachment to existing
      exercise equipment allows selection of the degree of anterior shear placed on the
      knee during exercise, ranging from a value which apparently places minimal stress
      on ligamentous restraints, through intermediate shear levels, to a value nearly
      that of standard exercise equipment. The special problems associated with
      anterior cruciate ligament (ACL) involvement are reviewed in terms of ACL
      function, failure, and healing. Calculated loading configurations illustrate the
      effect on shear afforded by the device. A pilot roentgenographic study indicates
      restoration of normal tibiofemoral alignment and joint surface velocity vectors
      during isometric extension with the device. This preliminary finding correlates
      with clinical observation. Clinical application includes isokinetic exercise of
      the chronically lax knee and rehabilitation of the knee after ACL repair or
      reconstruction. J Orthop Sports Phys Ther 1982;4(1):23-31.

PMID- 18810117
TI  - Initial management of acute ankle sprains with rapid pulsed pneumatic compression
      and cold.
AB  - Sports medicine practioners must be prepared to aggressively treat
      musculoskeletal trauma with both therapeutically sound and time efficient
      regimens. Thorough early treatment is essential for prevention of further trauma,
      for an expedient recovery, and for the earliest possible return to activity. The
      present study sought to evaluate the efficacy of rapid pulsed pneumatic
      compression along with cold in the amelioration of the acute symptoms associated
      with lateral ankle ligament sprains. Active range of motion and volumetric
      measures of ankle edema were made before and after 20-minute compression
      treatments on a series of 19 acute grade I lateral ankle ligament sprains. The
      number of treatments required before initiation of rehabilitation exercise ranged
      from one to eight with a mean of three. Rapid pulsed pneumatic compression along
      with cold is a safe and therapeutically sound method of controlling pain, loss of
      motion, and edema associated with this common injury. J Orthop Sports Phys Ther
      1982;4(1):39-43.

PMID- 18810118
TI  - A case study: the need for evaluation and reevaluation of acute ankle injury.
AB  - Although physical therapists are not trained to "diagnose, " it is essential that
      they possess competent evaluation skills and the ability to form accurate
      impressions which are then treated accordingly. This is especially true when the
      physical therapist is the first line of professional intervention in treating
      injury. Emphasis of this case report is not on new or unusual evaluation
      treatment techniques. Rather, the key to efficient care of the athlete lies in
      the perseverance of the health care professional in reevaluation, appropriate
      precautions, and adequate follow-up. J Orthop Sports Phys Ther 1982;4(1):44-46.

PMID- 18810119
TI  - Review of Repairs of Defects in Articular Cartilage: Part II *.
AB  - A review of the literature was undertaken to determine the extent and nature of
      the repair of articular cartilage. While repair is normally limited, under
      appropriate conditions the repair process appears to be of clinical significance.
      J Orthop Sports Phys Ther 1982;4(1):6-15.

PMID- 18810120
TI  - The evaluation of facial, head, neck, and temporomandibular joint pain patients.
AB  - The purposes of this paper are 1) to present an evaluation procedure for patients
      with signs and symptoms of temporomandibular joint (TMJ) pain dysfunction
      syndrome (PDS) and 2) to describe the findings of the evaluation procedure on 12
      patients with TMJ PDS. The evaluation emphasizes the collection of subjective and
      objective data. Records from 12 patients with facial, head, and neck pain were
      reviewed. The most frequent symptoms were: headache (1 00%), neckache (83.3%),
      and ear pain (58.3%). The most frequent signs were: muscle tenderness (100%) and
      mandibular deviation on opening (66.7%). Subjects with lateral pterygoid muscle
      tenderness had digastric muscle tenderness as well. Subjects with medial
      pterygoid muscle tenderness had masseter and hyoid muscle tenderness. Masseter
      muscle tenderness was strongly related to sternocleidomastoid and mylohyoid
      muscle tenderness and neckache. J Orthop Sports Phys Ther 1982;3(4):193-199.

PMID- 18810121
TI  - The variable lumbar orthosis: fabrication and guidelines for use.
AB  - When treating the patient complaining of low back pain, the physical therapist
      may decide to support the lumbar spine through the temporary use of a lumbar
      orthosis. In severe cases (generally involving fracture or instability) the goal
      of orthosis application may be immobilization or significant limitation of
      movement. In less severe cases the goal is generally the reduction of spinal
      stress by the application of supportive pressure to the abdomen and by supporting
      a flexed, neutral, or extended position of the lumbar spine. A variety of
      orthoses is commercially available. These include rigid orthotics and body casts,
      various types of corsets, elastic binders with molded plastic inserts, and all
      elastic binders. To date, however, we have not encountered a commercially
      available orthosis which provides abdominal support and lumbar positional support
      which can be varied by the patient in order to meet his changing biomechanical
      needs as he changes body position. This report describes a variable lumbar
      orthosis that we have fabricated and utilized in our clinic with favorable
      results. J Orthop Sports Phys Ther 1982;3(4):206-208.

PMID- 18810122
TI  - An introduction to the plica.
AB  - Physical therapy literature has been void of information concerning the plica.
      The authors discuss the literature available past and present. Using current
      published information and clinical experience, the authors have described the
      functional anatomy, the evaluation, the surgery, and the prevention and
      postoperative rehabilitation programs. Case studies were used to demonstrate
      conservative and nonconservative approaches in treating the plica syndrome. J
      Orthop Sports Phys Ther 1982;3(4):171-177.

PMID- 18810123
TI  - Trunk Testing Using a Prototype Cybex II lsokinetic Dynamometer Stabilization
      System.
AB  - This pilot study represents Cybex II isokinetic dynamometer trunk testing on 160
      subjects (98 males, 62 females). A prototype apparatus which provides
      stabilization in the standing (functional) position was used in the testing. The
      testing protocols were performed first for trunk flexion and then trunk
      extension. The protocols consisted of two isometric tests for 5 seconds at 0
      degrees trunk angle and 45 degrees trunk angle followed by three repetitions each
      at the isokinetic speeds of 30, 60, 90, and 120 degrees per second. Peak torque
      values were measured for the isometric tests. lsokinetic data interpretation
      consisted of: peak torque, time rate of tension development, range of motion
      where peak torque occurred, and total work performed. The ratios of trunk flexors
      to extensors at each test were also calculated. The conclusion from this pilot
      study is that the use of an isokinetic testing of trunk musculature and
      establishing normative data provide clinically useful guidelines for sports
      screening, industrial medicine screening, and objective parameters for
      discharging patients with trunk dysfunction. J Orthop Sports Phys Ther
      1982;3(4):164-170.

PMID- 18810124
TI  - lontophoresis for Treatment of Shinsplints*.
AB  - It was hypothesized that shinsplints are the result of muscle inflammation
      induced by overuse; thus, as an inflammatory response, the application of an
      antiinflammatory medication to the involved muscles would eliminate the pain of
      shinsplints. The application of hydrocortisone by iontophoresis was effective in
      the elimination of shinsplint pain in 18 cases of shinsplints involving four male
      and eight female athletes. J Orthop Sports Phys Ther 1982;3(4):183-185.

PMID- 18810125
TI  - Academics versus Teachers: A Dilemma in Physical Therapy Education.
AB  - "These excerpts from the text of the Advisory Council on Physical Therapy
      Education, October 22, 1981, express the concerns of many clinical and research
      physical therapists about the current trends in physical therapy education.
      Although Dr. Rose makes a controversial assumption that effective educators need
      no formal training in educational process, I believe Dr. Rose's comments deserve
      our attention." Dennis L. Hart, MPA. PT J Orthop Sports Phys Ther 1982;3(4):160
      163.

PMID- 18810126
TI  - Factors related to extension lag at the knee joint.
AB  - Twenty patients were examined in an investigation of the relationships between
      extension lag at the knee and other measures taken from the injured and uninjured
      extremity. The results of the study show: 1) there were no significant
      correlations between extension lag and the depth of squat, the extension force or
      flexion force, the circumference at the joint line or the circumference 5 and 15
      centimeters cephalad to the patella pole, and active or passive knee flexion; 2)
      that the mean for flexion force was greater than the mean for extension force in
      the injured extremity, and there was no difference between the means for flexion
      and extension force in the uninjured extremity; and 3) that the means of the
      measures for active and passive flexion, flexion force, and circumference
      measures of the thigh taken from a group of patients who had stiff rotational
      movements at the tibiofemoral joint.were different from the means of the same
      measures taken from a group of patients who had normal rotational movements.
      There is limited evidence to suggest that weakness of the quadriceps muscle may
      be a factor in extension lag at the knee, but the support for this conclusion is
      based on comparison between groups of patients and not from the correlations
      between other variables and extension lag. For future studies, it is recommended
      that an attempt be made to secure patients with extension lags greater than 3Oin
      an effort to improve the prospect of detecting any relationships.J Orthop Sports
      Phys Ther 1982;3(4):178-182.

PMID- 18810127
TI  - Role of endorphins in pain modulation.
AB  - This paper describes a brief history of endorphins and the current theories on
      the role of endorphins in pain modulation. The use of physical therapy modalities
      for pain control and the interaction of endorphins may also be implicated. J
      Orthop Sports Phys Ther 1982;3(4):200-205.

PMID- 18810128
TI  - Review of the repair of defects in articular cartilage: part I *.
AB  - A review of the literature was undertaken to determine the extent and nature of
      the repair of articular cartilage. While repair is normally limited, under
      appropriate conditions the repair process appears to be of clinical significance.
      J Orthop Sports Phys Ther 1982;3(4):186-192.

PMID- 18810129
TI  - The diverse use of foam rubber in a physical therapy department.

PMID- 18810130
TI  - Effect of lower extremity asymmetry on the kinematics of gait.
AB  - The purpose of this study was to determine the effect of lower extremity
      asymmetry on the kinetic energy of the leg segments during ambulation. The
      equalization of leg length by means of a lift equalized the time durations for
      the four phases of a gait cycle. Leg length equalization also decreased the
      kinetic energy of the lower extremity segments for both legs despite a difference
      in the segmental masses of the two legs. J Orthop Sports Phys Ther 1982;3(3):105
      107.

PMID- 18810131
TI  - Rehabilitation for anterior instability of the knee: preliminary report.
AB  - Anterior instability of the knee and its associated rotatory components is
      recognized as a common disabling knee problem in athletes and nonathletes. The
      spectrum of anterior instability begins with injury to the anterior cruciate
      ligament as an isolated event or as part of an injury complex. Within the genera
      classification of anterior instability are straight, anteromedial, anterolateral,
      and combined. The type of instability is recognized in relation to the relative
      movement of the tibia on the femur and the rotational position of the tibia
      relative to the femur when an anteriorly directed force is applied to the tibia.
      The status of the static stabilizers of the knee dictates the type of
      instability. Treatment following anterior cruciate injury depends upon the extent
      of injury. Where significant disability and instability exist, reconstructive
      surgery utilizing intracapsular and/or extracapsular repairs can be performed.
      Rehabilitation begins at the time of injury and continues throughout life. The
      rehabilitation program should attempt to: 1) minimize risks of reinjury; 2)
      educate the patient; 3) reinforce stability with exercise based on biomechanical
      principles; 4) prevent or prolong the subsequent onset of degenerative changes;
      and 5) reinstate the previous performance level. J Orthop Sports Phys Ther
      1982;3(3):121-128.

PMID- 18810132
TI  - An electromyographic analysis of the effectiveness of heat or cold and stretching
      for inducing relaxation in injured muscle.
AB  - This study examined the use of heat and cold therapy in conjunction with either
      static stretching or a technique of proprioceptive neuromuscular facilitation
      stretching to determine which combination of these treatment techniques would
      elicit the greatest amount of relaxation in muscle which exhibits delayed,
      postexertional pain as indicated by changes in levels of EMG activity. Results
      indicated I) a strenuous exercise task can produce an increase in electrical
      activity and is considered to be effective in inducing experimental muscle pain;
      21 the use of cold followed by static stretching appeared to be superior to other
      treatments in reducing delayed muscle pain; 3) treatments involving the use of
      cold followed by some type of stretching are more effective than treatments
      involving heat and stretching for inducing muscle relaxation; 4) treatments
      involving static or proprioceptive neuromuscular facilitation stretching appear
      equally effective in reducing muscle pain; and 5) subcutaneous fat may serve as a
      type of insulation against the penetrative effective of heat or cold therapy.J
      Orthop Sports Phys Ther 1982;3(3):133-140.

PMID- 18810133
TI  - The superior tibiofibular joint: the forgotten joint.

PMID- 18810134
TI  - Physical therapy evaluation of the shoulder complex in athletes.
AB  - A systematic approach is presented for evaluating the shoulder complex in
      athletes. The evaluation is divided into two parts: the subjective and objective
      examinations. The evaluation will determine the severity of the injury, the
      irritability of injury, and the structural involvement, and provide objective
      data for designing a comprehensive program of rehabilitation. J Orthop Sports
      Phys Ther 1982;3(3):108-120.

PMID- 18810135
TI  - Accessories included.

PMID- 18810136
TI  - The effect of vertical dimension on muscular strength.
AB  - The purposes of this investigation were to determine 1) if there was a difference
      in systemic muscular strength as mandibular position was varied in apparently
      normal subjects, and 2) if muscle strength changed, were these changes related to
      a history of pain or discomfort associated with the temporomandibular joint or to
      a clinical examination of certain muscles at the head or neck. Twenty-seven
      subjects filled out a screening questionnaire designed to determine a history of
      pain or discomfort associated with the head and neck. All subjects were examined
      for muscle tenderness to palpation and occlusal discrepancies. Each subject was
      tested for muscular strength on the Cybex II-Data Acquisition System while their
      vertical dimension of occlusion was altered. The data did not support either
      research hypothesis. Twenty-three of 2 7 (85%) subjects had medial pterygoid
      tenderness and 25 of 2 7 (93%) subjects had lateral pterygoid tenderness. Only
      one subject was asymptomatic to muscle palpation. It appears that many apparently
      normal individuals are symptomatic to muscle palpation. J Orthop Sports Phys Ther
      1981;3(2):57-61.

PMID- 18810137
TI  - Comparison of Quadriceps and Hamstring Torque Values during lsokinetic Exercise.
AB  - Maximal voluntary muscular torque output of the quadriceps and hamstrings during
      isokinetic exercise was studied. Both knees of 50 male and 50 female subjects
      between the ages of 25 and 34 were tested at 60, 180, and 300" per second on the
      Cybex II isokinetic dynamometer. The means, standard deviations, ranges, absolute
      value differences, and analysis of variance were calculated on the torque values.
      The findings were that 1) torque values decreased as speed of exercise increased;
      2) quadriceps torque values were significantly greater than the hamstrings at
      each test speed; 3) the ratio of hamstring torque values to quadriceps torque
      values significantly increased as the test speed increased; 4) dominant and
      nondominant knee torque values differed significantly for the males but not for
      the females; 5) the ratio of nondominant to dominant knee torque values was equal
      to or greater than 97% in all tests; and 6) the absolute difference in torque
      values between each subject's knees was 12 foot-pounds or less. J Orthop Sports
      Phys Ther 1981;3(2):48-56.

PMID- 18810138
TI  - lsokinetic Torque Outputs of Professional and Elite Amateur Ice Hockey Players.
AB  - Instrumentation advances have recently allowed the isokinetic evaluation of
      muscle function for purposes of injury diagnosis, rehabilitation, and training
      prescription. This type of evaluation has been particularly useful for athletes
      in preparing for performance or returning to training following injury.
      lsokinetic testing of specific muscle groups and at the approximate limb speeds
      required for performance of the sport has allowed more specific analysis of the
      functional strengths and weaknesses of athletes. Isokinetic testing allows
      comparison of agonist and antagonist muscle groups for balance across a joint,
      for right and left side muscle group comparison, and for joint angle at peak
      torque. Several athletic groups have already been characterized; alpine skiing,
      track and field (sprinting, jumping, and walking), and orienteering. The purpose
      of this study was to evaluate the function of important muscle groups for the
      performance of ice hockey. The data provided the basis for devising a training
      program for the athletes and also provided data for the characterization of
      professional (NHL) and elite amateur (Olympic) ice hockey players. Analysis also
      provided comparative information about the two groups.J Orthop Sports Phys Ther
      1981;3(2):42-47.

PMID- 18810139
TI  - Displaced disc preventing mandibular condyle translation: mobilization technique.
AB  - The temporomandibular articulation is briefly reviewed. Limited mandibular
      opening due to disc displacement is explained. A mobilization technique and
      associated dental procedures necessary to restore function and structure to this
      area are described. J Orthop Sports Phys Ther 1981;3(2):62-66.

PMID- 18810140
TI  - Active-passive hand apparatus.

PMID- 18810141
TI  - A case report: effect of a leg length differential on oxygen consumption.

PMID- 18810142
TI  - Effects of immobilization and exercise on articular cartilage-a review of
      literature.
AB  - Physical therapists evaluate and treat patients with limited or absent range of
      motion of joints. This limitation of joint range of motion may be secondary to
      diseases affecting the musculoskeletal system or therapeutic intervention such as
      splinting or casting. Soft tissue, bony, and cartilaginous changes occur when
      joints are immobilized or exercised. Therefore, the effects of immobilization and
      exercise on articular cartilage should be understood by therapists who attempt to
      restore joint motion. A review of the literature is presented. J Orthop Sports
      Phys Ther 1981;3(1):2-5.

PMID- 18810143
TI  - Case study: myofascial pain of the posterior shoulder relieved by spray and
      stretch.
AB  - This article presents the rationale for the use of the spray and stretch
      technique for commonly found myofascial pain syndromes. General principles of
      this technique are briefly discussed, with emphasis on shoulder pain patterns.
      The muscles which cause anterior shoulder pain and middle deltoid pain are
      discussed. The muscles which cause posterior shoulder pain are examined as part
      of the case study. The case study describes posterior shoulder pain with
      radiation down the back of the upper arm and down the ulnar side of the forearm.
      The specific pain pattern for the subscapularis is presented. Muscles potentially
      referring pain to the back of the shoulder are described both for examination and
      treatment. Results and follow up are reported. J Orthop Sports Phys Ther
      1981;3(1):21-26.

PMID- 18810144
TI  - Limb length discrepancies of the lower extremity (the short leg syndrome).
AB  - A survey of over 4,000 athletes and long distance runners, seen in my office over
      the past 6 years, reveals almost 40% of some form of limb length discrepancy. The
      limb length discrepancy is oftentimes associated with functional abnormalities,
      such as overpronation of one foot in contradistinction to the other or imbalances
      within the pelvis itself. Likewise, anatomical or true shortness may be present
      or a combination of anatomical and functional discrepancies. There appears to be
      a high correlation of injury on the short leg side and also associated weakness
      with the shortening. Conversely, utilizing a heel lift for a functional problem
      may cause contralateral symptoms. That being the case, it appears appropriate for
      practitioners involved in treating athletes to be aware of the various forms of
      limb length discrepancies that may exist, their significance, and their
      appropriate treatment. J Orthop Sports Phys Ther 1981;3(1):11-16.

PMID- 18810145
TI  - Preseason screening of the lumbar spine.
AB  - The author proposes a step-by-step method of lumbar spine examination which can
      be incorporated into the large scale preseason athletic participation screening
      process. This paper lists and describes examination techniques which can be
      administered quickly and accurately to large numbers of athletes in succession.
      In addition, the paper delineates two levels of proficiency required to perform
      the examination, outlines a practical format, and discusses general and specific
      precautions and contraindications to participation. J Orthop Sports Phys Ther
      1981;3(1):6-10.

PMID- 18810146
TI  - Myositis ossificans: report of an unusual case*.
AB  - A particularly large bone resulting from myositis ossificans was found in an
      unusual location, the semimembranosus. Consideration of the radiographic and
      histological diagnoses are discussed. The importance of being able to diagnose
      this lesion in young athletes is stressed. J Othrop Sports Phys Ther
      1981;2(4):184-186.

PMID- 18810147
TI  - Cybex II-Data Acquisition System.
AB  - The purpose of this paper was to describe a mechanical system that can be used to
      accurately and objectively record muscle torque and its reliability. The system
      includes a Cybex II dynamometer and a simple microprocessor that digitalizes the
      analog signal from the Cybex II. Therefore, the system eliminates the
      subjectivity of reading the torque recording from the typical Cybex II paper
      recording. After digitalizing the analog signal from the Cybex II, the Cybex 11
      Data Acquisition System determines the maximum torque in millivoltage and
      displays the maximum millivoltage recorded over a specified time period.
      Reliability of the system for dead weights was r = 0.99 (P </= 0.05). The data
      acquisition system in conjunction with the Cybex II dynamometer was confirmed as
      accurate instrumentation for the measurement of loads applied to the Cybex II. J
      Orthop Sports Phys Ther 1981;2(4):177-179.

PMID- 18810148
TI  - Soft-tissue coverage for severe defects of the lower extremity*.
AB  - Soft-tissue defects of the lower extremity usually result from trauma, infection,
      vascular insufficiency, or surgery. In the past, defects that could not be
      treated by primary closure or skin grafts have been allowed to "fill in"-a slow
      process of granulation, contraction, and epithelialization. Some defects have
      been treated in multistaged flap procedures, which are time-consuming and
      expensive. In recent years, two new methods of tissue transfer have greatly
      improved our ability to close these difficult wounds and to rehabilitate these
      patients: muscle flaps and free flaps. J Orthop Sports Phys Ther 1981;2(4):160
      162.

PMID- 18810149
TI  - Cybex II Hip and Trunk Stabilization during Quadriceps/Hamstring Evaluation.
AB  - The purpose of this paper is to suggest a restraint system that can be used
      during the use of a Cybex II in testing the quadriceps and hamstrings.
      Information suggests that torque values can be affected without the use of a
      restraint system. J Orthop Sports Phys Ther 1981;2(4):191-193.

PMID- 18810150
TI  - Electrotherapeutic Approach to Postoperative Pain following Total Hip
      Replacement: A Case Study.
AB  - Persistent pain following unilateral total hip replacement was approached with
      multiple electrical modalities. lontophoresis, with several ions for specific
      physiological effects, was utilized successfully. When skin irritation was
      encountered, high frequency sine wave, i.e., 1 kilohertz, was substituted because
      of its nonirritating, deep penetration qualities. Ultrasound was also utilized as
      an adjunct in the attempt to introduce the chemicals previously introduced by
      iontophoresis by way of the phonophoretic process. TENS was applied at home
      between office visits to maintain pain control but was not, apparently, involved
      in the overall rehabilitative process of the pathological conditions, since no
      lasting analgesic effects were noted. Traditional electrical stimulation
      techniques were added to the program when specific muscular weakness was noted,
      using surged sine wave at 1 kilohertz to the affected musculature. The favorable
      results of this multiphasic approach are clearly demonstrated in the relatively
      pain-free, functional activities of the patient. J Orthop Sports Phys Ther
      1981;2(4):180-183.

PMID- 18810151
TI  - The new challenges of physical therapy for external fixation treatment of
      fractures*.
AB  - External fixation, the restoration of skeletal integrity using pins connected by
      an external support, had its birth in the mid- 1800's. Recent improvements have
      caused a resurgence of interest in this art when dealing with complicated
      fractures. The health team is involved in enhancing the benefits gained from this
      method of fracture management. The physical therapist works in conjunction with
      the orthopaedic surgeon to achieve maximal rehabilitation of the injured limb.
      Rehabilitation includes functional training and education concerning limitations
      and daily care of the patient apparatus. J Orthop Sports Phys Ther 1981;2(4):171
      176.

PMID- 18810152
TI  - Electromyographic Analysis of the Lower Extremity during Pedaling*.
AB  - EMG activity in the gluteus maximus, rectus femoris, biceps femoris, vastus
      lateralis, gastrocnemius, and anterior tibialis muscles was studied in six
      healthy male subjects. Each subject pedaled against changes in workload, pedaling
      rates, and different weight flywheels, with and without toe clips and from both
      sitting and standing positions. All the muscles tested were shown to be active at
      workloads greater than 300 kilograms per minute. In addition, the amplitude of
      the EMG signals increased with increasing workloads. No real differences in
      muscle activity timing were found between the light and heavy flywheels or
      between the competitive and noncompetitive cyclists. Standing while pedaling
      produced increased activity in the rectus femoris and vastus lateralis at high
      rpm and low workloads. J Orthop Sports Phys Ther 1981;2(4):163-170.

PMID- 18810154
TI  - A case study: application of ultrasound to determine a stress fracture of the
      fibula.
AB  - A female with a diagnosis of acute ankle sprain was evaluated for physical
      therapy treatment. Although radiological evidence was negative, the patient's
      history and symptoms suggested a stress fracture of the fibula. Application of
      ultrasound intensified the pain when directed to a specific point on the fibula.
      At a later date, subsequent radiological evidence indicated a stress fracture at
      the point of maximum sensitivity to ultrasound. J Orthop Sports Phys Ther
      1981;2(3):134-136.

PMID- 18810153
TI  - An alternative management protocol for lateral ankle sprains*.
AB  - Soft tissue ankle injuries, particularly lateral ligament sprains, cause
      considerable disability and loss of time from activities. These injuries are
      commonly and frequently treated by physical therapists. Controversy exists over
      the efficacy of various methods for the nonoperative management of these
      injuries. A comprehensive program for the management of the lateral ankle sprain,
      involving the fabrication of a thermoplastic ankle stirrup and the initiation of
      a selfdirected home program of ankle rehabilitation using surgical tubing, is
      detailed. Based upon the experimental work of Brostrom, Noyes, and others, the
      early application of stress with protective motion has been found to facilitate
      the strength and structural integrity of healing ligaments. The ankle stirrup
      regimen allows weight bearing and easy removal for treatment or exercise. Joint
      stiffness, muscular atrophy, and circulatory stasis are minimized. The ankle
      stirrup provides an aggressive yet therapeutically sound approach to the
      management of this injury. J Orthop Sports Phys Ther 1981;2(4):187-190.

PMID- 18810155
TI  - Comparison of Electromyographic Activity in Normal Lumbar Sacrospinalis
      Musculature during continuous and Intermittent Pelvic Traction.
AB  - This study investigates whether there is a difference in electromyographic
      activity in the lumbar sacrospinalis musculature during continuous and
      intermittent pelvic traction. Twenty-nine normal subjects were randomly assigned
      to a control group, a continuous traction group, or an intermittent traction
      group. Electromyographic activity was recorded at specific timed intervals.
      Myoelectric activity increased with the onset of either type of traction, but by
      the third recording both groups had returned to their normal initial resting
      myoelectric recordings. The myoelectric patterns over time were similar for the
      two treatment groups. No significant difference in electromyographic activity of
      the lumbar sacrospinalis musculature during intermittent or continuous pelvic
      traction was found. J Orthop Sports Phys Ther 1981;2(3):137-141.

PMID- 18810157
TI  - Diagnosis and treatment of injury to the anterior cruciate ligament *.

PMID- 18810156
TI  - Patellofemoral pain syndromes: a comprehensive and conservative approach.
AB  - Among 7,785 patients examined with knee problems, 370 were diagnosed with
      patellofemoral pain syndromes. Examination and treatment were performed using a
      systematic approach. The patients were placed on a conservative program
      consisting of a four-stage progression, with the goal of relieving symptoms and
      returning to full activity. The results of this approach showed that 77%
      recovered. to a satisfactory level and 23% were unsatisfactory and underwent
      surgical procedures. J Orthop Sports Phys Ther 1981;2(3):108-116.

PMID- 18810158
TI  - The straight-leg-raising test: a review*.
AB  - A positive unilateral straight-leg-raising sign is routinely interpreted as
      indicative of a "disc lesion. " A review of the literature was undertaken in an
      attempt to more clearly illustrate the mechanisms and results of the straight-leg
      raising test. It was found that a positive straight-leg-raising test has minimal
      value in differentiating a patient with herniated disc from other patients with
      love back pain and sciatica. J Orthop Sports Phys Ther 1981;2(3):117-133.

PMID- 18810159
TI  - A study of anatomical factors involved in shinsplints.
AB  - This study identifies the anatomical factors involved in shinsplints. The
      investigation was confined to the identification of select anatomical factors
      common to female subjects who develop shinsplints. The height of the longitudinal
      arch of the foot, pronation of the foot, and ratio of body weight to height was
      correlated with the incidence of shinsplints. Within the limits of the study,
      only foot pronation was significantly related to the incidence of shinsplints. J
      Orthop Sports Phys Ther 1980;2(2):55-59.

PMID- 18810160
TI  - The relationship of foot pronation, foot position, and electromyography of the
      anterior tibialis muscle in three subjects with different histories of
      shinsplints.
AB  - This study determines the relationship between foot position, foot pronation, and
      quantitative electromyography of the anterior tibialis muscle for three female
      subjects with contrasting histories of shinsplints. The subject with a chronic
      shinsplint problem had the greatest degree of foot pronation, which resulted in
      an increased stress of the anterior tibialis muscle. Stress in this muscle was
      associated with the occurrence of shinsplints. No conclusion was made regarding
      foot position and shinsplints. J Orthop Sports Phys Ther 1980;2(2):60-64.

PMID- 18810161
TI  - Critically reading a research article*.
AB  - This paper presents a method for critically reading a research article. Emphasis
      is placed on the specific format of the question being asked, the control of
      variables to ensure internal and external validity, selected basic rules for
      applying statistics, and the justification for specific conclusions drawn by the
      investigator. The method is designed to be clinically relevant with the final
      evaluation stressing improved patient care. This format has been effectively used
      by students of the Department of Physical Therapy at the Medical College of
      Georgia for critiquing literature. J Orthop Sports Phys Ther 1980;2(2):72-76.

PMID- 18810162
TI  - Selection of a running shoe: if the shoe fits - run *.
AB  - National consciousness for physical fitness through running has propelled the
      creation of a new athletic shoe. The long distance running shoe or flat was
      designed to protect the foot from the rigors of long distance running. The
      protective design of shoes is patterned from infancy. If the athletic shoe
      manufacturer recognizes the mechanics of gait, a complementary design will be
      gained. This paper presents growth, anatomy, mechanics of gait, and
      recommendations for athletic footwear.J Orthop Sports Phys Ther 1980;2(2):65-68.

PMID- 18810163
TI  - Team approach: a necessity for treating young athletes.
AB  - The high school years, when viewed as the beginning of an athletic career, can be
      the most crucial period in an athlete's life. Thorough, proper, and professional
      medical care at this level is essential; improper management of the developing
      athlete can seriously impair the individual's future in competitive sports. This
      paper describes a case extending over an 18-month period involving a young
      athlete who experienced recurring pain and distress in the left groin. Continued
      acceptance of the pain as a simple muscular strain precluded a thorough
      examination of the case history and the disorder itself. Thus, accurate diagnosis
      and proper treatment were made more difficult.J Orthop Sports Phys Ther
      1980;2(2):69-71.

PMID- 18810164
TI  - The foot and its relationship to gait: a series of articles and editorial
      comments.
AB  - The following series of articles by various authors is presented to inform the
      readers of some current concepts in biomechanics of gait and podiatric sports
      medicine. Better understanding of the contents should facilitate health care
      delivery in orthopaedic and sports physical therapy: 1) The Foot and Sports
      Medicine-Biomechanical Foot Faults as Related to Chondromalacia Patellae*David
      Ramig, DPM, Jay Shadle, DPM, C. Allen Watkins, DPM, Daniel Cavolo, DPM,Jeffrey R.
      Kreutzberg, DPM, PhD, RPT 2) The Foot and Chondromalacia-A Case of Biomechanical
      Uncertainty?Dr. J. G. P. Williams, Secretary General J Orthop Sports Phys Ther
      1980;2(2):48-54.

PMID- 18810165
TI  - Comparison of Electro-Myo Stimulation to lsokinetic Training in Increasing -Power
      of the Knee Extensor Mechanism *.
AB  - A clinical study of six individuals was set up to compare an Electro-Myo
      stimulation protocol to an isokinetic protocol. The objective of the study was to
      see which was more effective in increasing power in the knee extensor mechanism.
      Results of the study showed that isokinetics were superior to Electro-Myo
      stimulation in increasing power. One question that remained unanswered in the
      testing was whether a higher faradic current, if tolerated, would be more
      efficient in increasing the power of a muscle group than would isokinetics. J
      Orthop Sports Phys Ther 1980;2(1):20-24.

PMID- 18810166
TI  - The hypothesis of adding compression when examining and treating synovial
      joints*.
AB  - Synovial joints and their supportive structures are a common source of pain and
      discomfort, causing many people to seek medical advice and treatment. Ample
      clinical evidence exists to show that there are circumstances when, if joint
      movements are not tested through range while the joint surfaces are firmly
      compressed together, the information derived from the examination is inadequate.
      This paper deals with the clinical, anatomical, and pathological evidence related
      to pain that arises from within synovial joints, thereby validating the need,
      under certain circumstances, to incorporate a compression component into the
      testing of joint movements. An example of the use of the compression component in
      treatment is also presented. J Orthop Sports Phys Ther 1980;2(1):7-14.

PMID- 18810167
TI  - The relationship between subjective and objective measurements of strength *.
AB  - Manual muscle testing is utilized by physicians and physical therapists to aid in
      the diagnosis and evaluation of pathology.' The basis of a diagnosis or the
      modification of a treatment program is dependent upon the clinician's perception
      of a patient's strength. This inherent subjectivity of manual muscle testing
      often leads to questionable findings in a medical examination. Factors such as
      sex, age, height, and weight serve only to increase the subjectivity of this
      evaluation This study demonstrates the use of a new manual muscle testing unit
      (MMTU) to quantify muscle strength objectively. The results of the MMTU were
      compared to a clinician's subjective evaluation of the stronger limb. In
      addition, the data obtained with the MMTU were analyzed to investigate further
      what constitutes a significant strength deficit. The MMTU's ability to
      differentiate strength differences and deficits demonstrates how manual muscle
      testing can assume a refined role in the evaluation of muscle strength. J Orthop
      Sports Phys Ther 1980;2(1):15-19.

PMID- 18810168
TI  - Serial assessment and treatment of a humeral fracture.
AB  - Clinical problems at the glenohumeral joint, whether chronic or induced by
      trauma, tend to manifest joint hypomobility with accompanying. muscle weakness.
      Fractures at the proximal humerus tend to occur more frequently in older
      patients, but in the presence of violent trauma this injury may occur in the
      younger patient as well.' The initial treatment often includes some form of
      immobilization followed by remobilization and muscle strengthening. There is a
      clinical need to document the sequence and form of physical therapy treatment and
      quantitatively reflect changes in joint motion and strength. A case study of a
      patient with a proximal humeral fracture is presented to (a) dezcribe the
      clinical findings and treatment associated with a shoulder injury, (b) describe
      and illustrate some methods of assessment and treatment, and (c) report results
      for joint motion and muscle strength. The hope of the author is that this paper
      might provide an example of physical therapy evaluation and treatment for such a
      case and demonstrate a model for expected results. Further, this paper might be
      used as a teaching model for therapists who are unexperienced with this type of
      patient.J Orthop Sports Phys Ther 1980;2(1):25-34.

PMID- 18810169
TI  - Effect of angle of traction pull on upper trapezius muscle activity*.
AB  - Seven female subjects with no history of cervical trauma were subjected to
      intermittent cervical traction to determine the effect of angle of traction pull
      on upper trapezius muscle activity. The EMG of the upper trapezius muscle was
      recorded when a force of 30 pounds was applied at angles of 7 0 O, 25 O, and 35
      O. An intermittent traction cycle of 7-second duration for each phase was used
      for the contract-relax sequence. Statistical analysis revealed that a positive
      relationship existed between an increase in angle of pull and muscle activity. J
      Orthop Sports Phys Ther 1980;1(4):205-209.

PMID- 18810170
TI  - Sports medicine centers in the United States: the personnel, patients, and
      services.
AB  - Sports medicine in the United States is a rapidly expanding field. The movement
      of the public into organized and informal recreation and sports has stimulated
      the growth and sophistication of sports medicine. In the last 35 years, sports
      related injuries have received unprecedented interest. Numerous sports medicine
      centers (SMC) have been established to meet the increased demand for a
      specialized approach to the treatment of sports injuries. Three main functions of
      SMC's have been reported: 1) research into the causes of and possible prevention
      of sports injuries; 2) sports medicine education for physicians, medical
      students, allied medical professionals, coaches, and the public; and 3) care of
      the injured athlete including the areas of prevention, diagnosis, treatment, and
      rehabilitate.In the latter half of 1978, this investigator surveyed SMC's in the
      United States to identify the status of selected aspects of the operations and
      approaches to sports medical treatment at these centers and also to provide a
      profile of sports medicine centers. A listing of SMC's was generated and a
      specially constructed survey instrument was mailed to 85 centers. Of the centers
      identified for this study, 71 (83.5%) responded with either a completed survey or
      a letter of explanation. Of those 71 responding, 56 (79%) met criteria
      established for inclusion in the study. These criteria were that the SMC: 1)
      specialized in the care of athletic injuries, and 2) had a patient population
      presenting primarily participant sports-related injuries.J Orthop Sports Phys
      Ther 1980;1(4):222-225.

PMID- 18810171
TI  - On conversion reactions.
AB  - This article discusses the symptomatology of conversion reactions along with
      Freudian, behavioral, and holistic perspectives on their etiology. Factors
      influencing the incidence of conversion reactions and clues for identifying the
      disorder are presented.J Orthop Sports Phys Ther 1980;1(4):200-204.

PMID- 18810172
TI  - Evaluation of Undergraduate Physical Therapy Students' Comprehension of
      Maitland's Grades (I-IV) for Posterior Mobilization of the Glenohumeral Joint.
AB  - In this study, the instruction of undergraduate students in Maitland's grades (I
      IV) for posterior glenohumeral mobilization as a valid instructional goal was
      investigated. Undergraduate students were instructed in Maitland's mobilization
      grades I-IV at various joints before the experimentation. Students selected were
      mobilized by the instructor. A random assignment of grades was given to the
      instructor before mobilization. The mobilization subject secretly identified the
      grade as the mobilization was being videotaped. The videotape was played to the
      class of undergraduate students who were asked to identify the grades visually.
      The accuracy of the student's ability to identify the assigned grades visually
      and kinesthetically was determined to be within the projected 90% accuracy level;
      therefore, the hypothesis was substantiated.J Orthop Sports Phys Ther
      1980;1(4):214-221.

PMID- 18810173
TI  - A Comparison of Two Methods of raining on the Development of Muscular Strength
      and Endurance.
AB  - The purpose of this study was to compare the relative effectiveness of using
      traditional barbell equipment and Nautilus dynamic equipment on the development
      of muscular strength and endurance. The subjects, 22 college students, were pre
      and posttested on two 3-minute bouts of rhythmic isometric exercise. After
      pretesting, the subjects were assigned to two groups. For the next 5 weeks, all
      groups trained three times weekly, but one group trained using traditional
      barbell equipment and the second group used Nautilus dynamic equipment. Results
      indicated significant improvement as a result of training in both groups, but no
      significant differences were found between the two training methods or the groups
      by training interaction for any of the variables evaluated. J Orthop Sports Phys
      Ther 1980;1(4):210-213.

PMID- 18810174
TI  - Results of the task analysis study sports physical therapy section american
      physical therapy association.
AB  - A survey instrument containing 1 13 sports physical therapy job tasks was
      developed by a committee of experts at the Combined Sections Meeting, American
      Physical Therapy Association (APTA), in Orlando, FL, on February 8-1 1, 1978. The
      committee was assisted by the Committee on Competencies, APTA, and a
      representative from Courseware, Inc. The instrument was then sent to 1074 members
      of the Section for the purposes of identifying the clinical tasks in which
      competency is essential to practice effectively and of determining to what extent
      members are practicing these clinical tasks. Two major mailings were sent, in
      October 1978 and January 1979; 573 forms were returned for a response rate of
      53.4%. Seventy returned forms were not used because they were incomplete or
      incorrectly filled out (35), were not deliverable (23), or were sent to those
      that were no longer members of the Section (12). The response rate of usable
      forms was 50.1 %.J Orthop Sports Phys Ther 1980;1(4):229-238.

PMID- 18810176
TI  - III. Normal Joint Structures and their Reactions to Injury.

PMID- 18810175
TI  - Anatomy and function of the temporomandibular joint.
AB  - Function of the temporomandibular joint is based on the articular design,
      neuromuscular control and integrity of soft tissue elements that comprise the
      anatomy. Through the study of kinesiology and arthrokinematics the exact nature
      of movement is known and with some understanding of the deglutination and
      masticatory process, the overall function of the temporomandibular joint becomes
      apparent. The relationship of bony components, ligamentous structures, muscles,
      and neurology identifies both specific and nonspecific functions that are readily
      predictable. It is upon this relationship that investigations proceed when
      attempting to remediate dysfunctions of this much used articulation.J Orthop
      Sports Phys Ther 1980;1(3):145-152.

PMID- 18810177
TI  - Ankle injuries: anatomical and biomechanical considerations necessary for the
      development of an injury prevention program.
AB  - This article describes the anatomical and biomechanical principles necessary for
      the development of an ankle injury prevention program. The structures of the
      talocrural joint and the subtalar joint are discussed in detail. The biomechanics
      of these two joints are discussed and their relationship elucidated. The
      ligamentous structures of the ankle are discussed in detail. Evaluation of the
      ankle is discussed in conjunction with mechanisms of athletic injuries. Pertinent
      principles necessary for the development of an injury prevention program for the
      ankle are presented.J Orthop Sports Phys Ther 1980;1(3):171-

PMID- 18810178
TI  - Restoration of dorsi flexion after injuries to the distal leg and ankle.

PMID- 18810179
TI  - A comparison of the effects of fluid and electrolyte replacement schedules on
      work performance and circulatory stress in 30 members of a high school football
      team.
AB  - The effects of administration of glucose-electrolyte solution using three
      different schedules of administration were investigated in 30 high school
      football players. Environmental conditions during the experiment were 90-95
      degrees and 60-62% relative humidity. Schedule I consisted of consumption of
      fluid ad libitum. Schedule 2 consisted of administration of 120 milliliters of
      fluid every 15 minutes. Schedule 3 consisted of administration of 240 milliliters
      of fluid every 15 minutes. Fluid consumption during schedule 1 was 0.8 1 liters,
      0.96 liters during schedule 2, and 1.92 liters during schedule 3. Regardless of
      the schedule followed, weight loss remained approximately 3 kilograms. This
      deficit of fluid volume was reflected in all groups as a decrease in
      VO2max.VO2max decreased 31% in schedule 1, and 25 and 23% in schedules 2 and 3,
      respectively. Physical performance, also measured by time needed to complete a
      300-meter obstacle course, increased 36% in schedule 1 and decreased 13 and 28%
      in schedules 2 and 3, respectively.J Orthop Sports Phys Ther 1980;1(3):153-158.

PMID- 18810180
TI  - Muscle strength at the trunk*.
AB  - The purpose of this study was to determine the strength of trunk flexors and
      extensors in normal male subjects during isometric, concentric, and eccentric
      contractions. Subjects were tested in the sidelying position to minimize the
      effects of gravity. The pelvis and lower extremities were measured on a custom
      built force table (lowa Force Table). Muscle strength was expressed as a moment
      of force (external force times the moment arm) in Newton-meter (Nm) units.
      Greater Nm were registered in the muscle-lengthened position than in the muscle
      shortened position for all isometric contractions. The Nm registered for
      eccentric contractions always exceeded the Nm registered for concentric
      contractions of the same muscle group. The Nm registered during contractions of
      trunk extensors always exceeded the values obtained during corresponding modes of
      contractions (isometric, eccentric, and concentric) of trunk flexors.J Orthop
      Sports Phys Ther 1980;1(3):165-170.

PMID- 18810181
TI  - The national athletic injury/illness reporting system 3-year findings of high
      school and college football injuries*.
AB  - The National Athletic Injury/Illness Reporting System is a national surveillance
      system created from several workshops at which physicians, athletic trainers, and
      sports administrators shared their ideas for obtaining meaningful data. The
      primary objective was to provide a feasible and inexpensive mechanism for the
      continuous collection and analysis of information on sports-related injuries.
      Additionally, the project offers institutions and agencies a useful system of
      recordkeeping. NAIRS collects data on a wide range of sports, however, this
      report clarifies the risk of injury for high school and college football.
      Presented are data on neurotrauma, meniscus/knee sprains, and ankle sprains.
      Playing surface, surface hardness, surface friction, and shoe-turf interface were
      also examined. It was concluded that no helmet type or brand was associated with
      unusually high levels of risk. Artificial surfaces did not constitute an
      additional risk of significant concussion. An association between playing surface
      and the risk of knee and ankle injuries was observed. J Orthop Sports Phys Ther
      1979;1(2):103-108.

PMID- 18810182
TI  - Ultrasonic techniques for treatment of planter warts in athletes.

PMID- 18810183
TI  - Sports activities and their effects on high density lipoprotein cholesterol and
      coronary heart disease.

PMID- 18810184
TI  - II. Normal Joint Structures and Their Reaction to Injury.

PMID- 18810185
TI  - Psychological aspects of chronic pain.
AB  - This article considers psychological aspects of chronic pain, including pain that
      is purely physical in origin. The concept of the "pain lifestyle" is discussed,
      as well as the relationship between pain and vocational problems, marital
      problems, sexual difficulties, depression, anger, and the "pain-prone"
      personality. The article also describes the utility of behavioral treatment
      programs for treating chronic pain.J Orthop Sports Phys Ther 1979;1(2):76-82.

PMID- 18810186
TI  - The thoracic outlet syndrome: a protocol of treatment *.
AB  - A protocol of treatment for the physical therapy management of the thoracic
      outlet syndrome has been established at Amsterdam Memorial Hospital, Amsterdam,
      New York. Certain orthopaedic manual therapy procedures are utilized to increase
      the mobility of specific areas of the patient's shoulder girdle, upper thorax,
      and if indicated, the cervical and upper thoracic spine. Previous training in
      orthopedic manual therapy is a prerequisite to employing this approach to the
      treatment of the thoracic outlet syndrome. A total of eight anatomical structures
      are involved. This particular regime of manual therapy plus postural improvement,
      corrective exercises, improved body mechanics, and other procedures relating to
      the patient's activities of daily living have proven to be an effective method to
      relieve the signs and symptoms produced by this musculoskeletal entity.
      Paraesthesiae and numbness were the predominant symptoms of the patients that
      underwent treatment. The patients ranged in age from 2 7-60 years. J Orthop
      Sports Phys Ther 1979;1(2):89-99.

PMID- 18810187
TI  - The fractured femur: acute emergency care treatment.
AB  - The most effective emergency care for a fractured femur is the use of a
      mechanical type traction splint such as developed by Hare and described herein.
      After general emergency care guidelines using a well-designed properly applied
      device will lead to significant decrease in pain, marked decrease in morbidity
      and mortality, and general improvement in the level of the care of the injured
      athlete.J Orthop Sports Phys Ther 1979;1(1):53-58.

PMID- 18810188
TI  - Dysfunction of the sacroiliac joint and its treatment*.
AB  - A very common but frequently overlooked cause of pain in the low back is a result
      of leaning forward without adequately supporting the anterior pelvis. This allows
      the innominates to rotate slightly downwards on the sacrum with fixation and an
      apparent increase in the length of the legs, which in turn irritates the sciatic
      nerve. This commonly occurs bilaterally but may occur on just one side. Flexion
      of the innominate(s) on the sacrum restores function to the sacroiliac joint,
      causes an apparent shortening of the legs and gives excellent relief of pain in
      the low back and sciatic pain.J Orthop Sports Phys Ther 1979;1(1):23-35.

PMID- 18810190
TI  - I. Normal Joint Structures and their Reaction to Injury*.

PMID- 18810189
TI  - Measurement of ankle joint swelling using a figure of 8*.
AB  - The method of measuring joint swelling in a figure of 8 has the following
      advantages: 1) being readily reproducible, 2) measuring swelling at the various
      sites of ankle sprains, and 3) requires only a tape measure and marking pen.J
      Orthop Sports Phys Ther 1979;1(1):51-52.

PMID- 18810191
TI  - Classification of musculoskeletal spinal conditions*.
AB  - The aim of this article is to present and discuss the classification of
      musculoskeletal spinal conditions. The major classifications presented are
      muscle, joint, and nerve root. Many different conditions are presented under each
      of these major classifications with emphasis on those conditions commonly seen in
      a physical therapy clinic. The clinical picture of each condition is presented
      showing the significant findings in the history, structural, mobility,
      neurological, and palpation exams. Treatment suggestions are presented to help
      clarify the differences between conditions, and to stress the importance of
      evaluation and classification before planning treatment. The author also stresses
      the interrelationship and progressive nature of certain conditions.J Orthop
      Sports Phys Ther 1979;1(1):3-15.

PMID- 18810192
TI  - Lumbar traction*.
AB  - The aim of this article is to present and discuss: 1) types of lumbar traction;
      2) effects of lumbar traction; 3) indications and contraindications for lumbar
      traction; 4) effective lumbar traction techniques. There is a review of important
      points that have been presented in earlier literature, as well as the
      introduction of new ideas and concepts. A portion of this article deals with the
      rationale-of using lumbar traction for the treatment of herniated disc and other
      lumbar spinal nerve root syndromes. There is considerable discussion of poundages
      necessary to achieve therapeutic results. Detailed description of positioning is
      presented. The importance of the use of proper equipment for mechanical lumbar
      traction is stressed. That lumbar traction can be a beneficial treatment for
      certain musculoskeletal disorders is stressed, but that effective treatment is
      not as easy and simple to administer as it may seem. J Orthop Sports Phys Ther
      1979;1(1):36-45.

PMID- 18810193
TI  - Immediate care of ankle injuries.
AB  - Physical therapists have an excellent background to deal with immediate care of
      injuries, although they traditionally have not been involved with this aspect of
      patient care. The occurrence of ankle injuries in sports is high6 (42% of high
      school athletes had previous ankle sprains) and the effects immediate.
      Appropriate attention and acute care by a physical therapist can reduce the
      period of disability considerably. The following are immediate care "concepts"
      for the physical therapist to consider.J Orthop Sports Phys Ther 1979;1(1):46-50.

PMID- 18810194
TI  - Introduction. The evolution of the surgical management of vestibular schwannomas.

PMID- 18810195
TI  - History of vestibular schwannoma surgery.
AB  - Attempts of surgical removal of vestibular schwannomas started 150 years ago with
      major limitations in terms of diagnosis and understanding of the disease but also
      in respect of surgical technique and instrumentation. Then came Cushing followed
      by Dandy, two pioneers and legendary neurosurgeons who understood the natural
      history of the disease and set the landmarks of the current surgery of the
      cerebellopontine angle. In this century of medicine, results and expectations
      shifted from a life-threatening affection to the actual standard of cranial nerve
      preservation and conservation of quality of life. In this overview, it is shown
      how the standard of the current surgery came from two distinct medical cultures,
      otologists and neurosurgeons, respectively. Now and in the near future, these
      competencies will be gathered in multidisciplinary teams who will display the
      whole panel of the treatment options in order to offer the best individual
      solutions for the patients.

PMID- 18810196
TI  - Genesis and biology of vestibular schwannomas.
AB  - This review chapter is a synthesis of the recent literature about pathogenesis of
      schwannomas with emphasis on vestibular schwannomas (VSs). The cornerstone of
      cellular transformation and proliferation of Schwann cells toward schwannomas has
      been attributed to the nonexpression of normal schwannomin/merlin (S/M) by these
      cells. The understanding of this mechanism has been gained from molecular genetic
      studies of neurofibromatosis type 2 (NF2) patients, in whom mutations of a tumor
      suppressor gene (NF2 gene) was clearly identified. S/M is the normal NF2 gene
      product. Lack of normal S/M protein in the schwannoma cell is due to gene
      mutation in 50% of sporadic VSs. In the other cases, epigenetic factors or
      activation of protease cascade contribute to ineffective S/M. The exact
      interactions of S/M with extracellular matrix, membranous glycoprotein and
      cytoskeleton are not fully understood. However, it is recognized that these
      interactions activate several pathways that might regulate cell-cycle process,
      apoptosis and intercellular interaction. Apart from the involvement of the S/M
      pathway, the authors review the potential role of other genetic abnormalities and
      growing factors that are supposed to be involved in the pathogenesis of VS.
      Understanding the pathways of action and regulation of S/M may provide the basics
      for identifying potential therapeutic targets, which is of paramount importance
      for a better management of NF2 patients.

PMID- 18810197
TI  - Radiobiology, principle and technique of radiosurgery.
AB  - Stereotactic radiosurgery involves the use of precisely directed closed skull
      single-session radiation to create a desired radiobiologic response within the
      intracranial target with minimal effects to surrounding structures or tissues. It
      provided a way for physicians to administer high single doses of radiation to
      intracranial targets in patients with relative safety. Rapid advances in imaging
      and computer technologies in the last decade have resulted in development of a
      variety of different radiosurgery techniques and their wider applications. The
      Gamma Knife-, proton beam- and LINAC-based radiosurgery devices represent the
      three main radiosurgery systems. Successful clinical experience with radiosurgery
      for a diversity of applications has led to a re-examination of radiobiological
      principles. For radiosurgical doses, the response of the tumor or target tissue
      and the adjacent normal tissue seems determined predominantly by the supporting
      vasculature.

PMID- 18810198
TI  - Cerebellopontine cistern: microanatomy applied to vestibular schwannomas.
AB  - The microanatomy of the cerebellopontine cistern (CPC) is of interest to many
      surgeons and has been the subject of controversial works especially concerning
      the study of the subarachnoid space in the internal acoustic meatus (IAM). The
      CPC lies in the cerebellopontine angle between the brainstem, cerebellum and
      petrous bone. It contains in its upper part the trigeminal nerve with the
      superior petrosal vein. The cochleovestibulofacial bundle occupies the middle
      portion and lies between the pontomedullary sulcus and the IAM. The
      glossopharyngeal, vagus and accessory nerves are located in the inferior part of
      the cerebellopontine angle close to the vertebral artery and the posteroinferior
      cerebellar artery. The acousticofacial cistern is a lateral extension of the CPC
      in the IAM. The anatomy of the meningeal layers within the IAM is discussed
      especially concerning 'the arachnoidal cleavage plane' in acoustic neuroma
      surgery.

PMID- 18810199
TI  - Radiosurgery: operative technique, pitfalls and tips.
AB  - RATIONALE: From frame placement to dose administration, each step of the
      procedure must be optimized in every detail for better preservation of global
      precision, accuracy, safety and efficacy. METHODS: Quality control for
      resolution, accuracy and acquisition parameter optimization of both computed
      tomography (CT) scanners and magnetic resonance imaging (MRI) must be performed.
      Inaccuracies should then be quantified through systematic combination of MRI and
      CT in the radiosurgery planning system. Topography of petrous structures such as
      cochlea, vestibulum and facial nerve canal should be visible on the CT scan. T1
      weighted volumetric MRI pulse sequences (3DT1) show a contrast-enhanced signal
      that is useful for both the pons interface delineation in Koos III cases, and the
      canal ending. High-resolution CISS T2-weighted volumetric pulse sequences (3DT2)
      allow direct nerve visualization and give superior stereotactic definition
      attributable to their better resolution minimizing partial volume effects and to
      their lower magnetic susceptibility minimizing distortions. The 3DT2 pulse
      sequences with contrast injection, show improved distinction between the pons and
      the nerves due to signal differences within the schwannomas. Fat saturation pulse
      sequences are of interest in postmicrosurgery conditions. The previous technical
      requirements and the dose planning elaboration will be balanced depending on the
      lesion volume staging (Koos), treatment history (microsurgery), clinical
      condition (hearing quality), pathological context (NF2) or age of the patient.
      The recommended marginal dose is 11-12 Gy. Tumor volume delineation allows the
      calculation of conformity, selectivity and gradient indexes. These global indexes
      must be weighted according to the relationship to critical structures and
      functional status of the patient. CONCLUSIONS: As an exclusively image-guided
      surgical method, radiosurgery requires special attention in the choice of imaging
      modalities and their acquisition parameters need extreme care. Technical nuances
      during the elaboration of the dose planning itself will directly influence both
      the toxicity risk and the chance of cure.

PMID- 18810200
TI  - Extended middle cranial fossa approach for vestibular schwannoma: technical note
      and surgical results of 896 operations.
AB  - From 1976 to 2006, 896 vestibular schwannomas were operated on using an extended
      middle cranial fossa approach. With this approach, the operative field can be
      extended according to tumor size and the facial and cochlear nerves can be
      preserved more easily with cooperation between the neurosurgeon and ENT surgeon.
      The mortality rate among 896 vestibular schwannoma patients was 0.3%. In the 760
      initially operated vestibular schwannomas with total removal of the tumor, facial
      nerves were anatomically preserved in 715 or 94.1% of the cases. In 61.0% of 270
      cases in which hearing preservation was attempted, hearing was preserved, and in
      46.7% of those 270 cases useful hearing was preserved postoperatively. However,
      in the last 10 years the useful hearing preservation rate of the 140 attempted
      cases was 53.6%. Most of the complications of this approach were cerebrospinal
      fluid leakage; by using fat tissue, fibrin glue and spinal drainage from 1992 to
      2005, cerebrospinal fluid leakage occurred in 59 or 10.6% of 569 cases, with 13
      or 2.3% being repaired surgically. Moreover, in the last 10 years, the surgical
      results have improved along with improved surgical experience, improved
      instruments and better monitoring methods.

PMID- 18810201
TI  - Translabyrinthine approach for vestibular schwannomas: operative technique.
AB  - For large vestibular schwannomas (VSs) for which removal is the primary therapy,
      the goals are complete tumor resection and maintenance of normal neurological
      function. The authors analyzed their results about facial nerve preservation,
      extent of resection and complications following resection of large VSs via a
      widened translabyrinthine approach. Between 1991 and 2001, 110 patients with a
      unilateral large VS (Koos stage IV) were operated on using the same technique in
      the same institution. The main steps of the operative technique were detailed and
      the clinical outcomes analyzed and compared with the results that were extracted
      from matched series in the literature. The main postoperative complications were
      cerebrospinal fluid leakage through the scalp wound in 4%, cerebrospinal fluid
      rhinorrhea in 4% requiring surgical revision in 3%. One percent of meningitis, 1%
      of posterior fossa hematoma and 4% of transient lower cranial nerve palsies were
      observed. There was no death related to the surgery. Total tumor removal was
      achieved in 85% of cases, near-total in 11% and subtotal in 4% of cases. Sixty
      two percent of patients obtained normal to near-normal facial function (House
      Brackmann grades 1 and 2). The authors suggest that the translabyrinthine
      approach is a suitable route for the safe removal of large VSs.

PMID- 18810202
TI  - Management of large vestibular schwannomas by combined surgical resection and
      gamma knife radiosurgery.
AB  - In this report, we evaluated the treatment results of a combination of surgery
      and radiosurgery for large vestibular schwannomas. The series of 8 patients
      included in this study underwent surgery followed by radiosurgical treatment
      between January 2000 and January 2006. The patients included 5 males and 3
      females aged 24-78 years (mean age: 53 years). The average maximum diameter of
      the tumor was 40 (35-45) mm. At the time of radiosurgery, the treatment size
      became 18 (9-20) mm. The mean peripheral dose administered was 11.8 (range 11-13)
      Gy, and the mean dose administered in the centre of the tumor was 23.75 (22-26)
      Gy. The mean follow-up period was 46 months after radiosurgery. Excellent facial
      nerve function (House-Brackmann grade 1 or 2) was preserved in 7/8 patients
      (87.5%). In the case of large vestibular schwannomas, the combined management is
      one option for maintaining cranial nerve function and tumor growth control.

PMID- 18810203
TI  - The wait and see strategy for intracanalicular vestibular schwannomas.
AB  - To refine our therapeutic policy for intracanalicular tumors, we reviewed our
      series of patients who where initially treated conservatively. Forty-seven
      patients (22 men and 25 women) harboring an intracanalicular vestibular
      schwannoma were followed prospectively. Mean age at the time of inclusion was
      54.4 (20-71) years. The mean follow-up period was 43.8 months (+/-40 months)
      ranging from 9 to 222 months. Failure was defined as significant tumor growth
      and/or hearing deterioration that required a microsurgical or radiosurgical
      treatment. Failure was observed in 35 cases while a conservative treatment is
      still ongoing in 12 patients. Ten patients kept an unchanged tumor size (21.3%),
      while 36 patients experienced a tumor growth (76.6%), and 1 patient experienced a
      mild decreased tumor size (2.1%). Among the 40 patients who where available for
      hearing level study, 24 patients (60%) did not change their Gardner and Robertson
      hearing class. Fifteen patients (37.5%) experienced a >10-dB hearing loss and 2
      of them became deaf. One patient (2.5%) improved her hearing level from 56.3 to
      43.8 dB over a 39.5-month follow-up period. These data suggest that the wait and
      see policy exposes the patient to degradation of hearing and tumor growth. Both
      events may occur in an independent way in the middle-term period. This
      information has to be given to the patient, and a careful sequential follow-up
      may be adopted when the wait and see strategy is chosen.

PMID- 18810204
TI  - Recurrence of vestibular schwannomas after surgery.
AB  - The issue of recurrence of vestibular schwannomas is poorly studied by the
      surgical literature and is probably underestimated. Our own long-term
      retrospective analysis after translabyrinthine approach has indicated a 9.2%
      recurrence rate. This long-term event is mainly due to regrowth of microfragments
      that have been left in the operative field along the course of the facial nerve
      or at the surface of the pons. Management of recurrence depends on the tumor size
      and patient's condition. Our current policy is to propose a Gamma Knife
      radiosurgical treatment in eligible cases. Prospective long-term follow-up
      studies using serial MR imaging after radical removal should bring reliable data
      about the incidence of vestibular schwannoma recurrence.

PMID- 18810205
TI  - Morphological changes of vestibular schwannomas after radiosurgical treatment:
      pitfalls and diagnosis of failure.
AB  - RATIONALE: Evaluate the morphological changes following radiosurgery in order to
      better define failure parameters. METHODS: 332 non-neurofibromatosis type 2
      vestibular schwannomas not previously treated surgically or radiosurgically were
      subjected to Gamma Knife radiosurgery between 1992 and 2004 at the Gamma Knife
      Center in Marseille with at least three sequential MRI scans after radiosurgery.
      Five length measurements were systematically obtained. RESULTS: Mean follow-up
      was 4.6 years. Transient loss of contrast enhancement appeared in 213 patients
      (68%). Significant increase was present at 6 months in 178 patients. In 74
      patients, the volume at 3 years was still higher than on the day of radiosurgery
      but remained stable. Failure occurred in 16 patients. Most showed progressive
      growth at all MRI controls after radiosurgery but late failure after initial
      response was possible. CONCLUSIONS: Sequential MRI scans after radiosurgery are
      necessary. A progressive and continuous growth at 3 years is essential to make
      diagnosis of failure.

PMID- 18810206
TI  - Tissue changes after radiosurgery for vestibular schwannomas.
AB  - The specific effects of radiosurgery on brain tumor tissue are not well
      understood. We review several approaches that have been used to address this
      issue. Correlating the radiobiology of radiosurgery with the radioclinical
      outcome may help to understand these tissue changes. In vivo imaging
      investigations are usually performed with MRI, but the use of functional and
      metabolic imaging, such MR spectroscopy, positron emission tomography or single
      photon emission computed tomography may provide additional information on the
      effects of radiosurgery. Finally, histological observations represent an
      invaluable source of information, when systematically analyzed in their clinical
      context.

PMID- 18810207
TI  - Facial nerve outcome after microsurgical resection of vestibular schwannoma.
AB  - The risk of facial nerve palsy after microsurgical removal of vestibular
      schwannoma cannot be totally eradicated. Beyond the functional problem, patients
      have to overcome the consequences of cosmetic disturbances, particularly the
      psychosocial difficulties and the decrease in quality of life due to this palsy.
      Taken together, the data from our personal experience and analysis of the
      literature indicate that the major predictor of postoperative facial deficit is
      tumor size. This information must be given to the patient when counseling for
      treatment option. When confronted with large tumors, we personally changed our
      surgical goals and considered that facial nerve conservation and tumor control
      are interconnected priorities instead of radical removal.

PMID- 18810208
TI  - Facial nerve function insufficiency after radiosurgery versus microsurgery.
AB  - BACKGROUND: Due to the synergic role of the facial nerve and the nervus
      intermedius in the mechanical protection of the eye and taste, vestibular
      schwannomas and/or their treatment may prove to be dangerous for the visual
      function and taste. Our goal was to evaluate and compare the impact of the tumor
      itself and the impact of microsurgery (MS) or Gamma Knife radiosurgery (GKS).
      MATERIALS AND METHODS: A functional questionnaire evaluating, among other items,
      patient complaints related to the eye and taste has been given out to a series of
      200 patients 3 years after the GKS of a unilateral vestibular schwannoma not
      previously resected. Their answers were compared with those of a group of 200
      patients operated on microsurgically. A Schirmer test was additionally performed
      before radiosurgery (RS) and more than 2 years after RS in 66 patients. RESULTS:
      The risk of dry eye and burning eye is much higher in patients operated by MS
      compared to patients operated by GKS due to the high incidence of facial palsy
      (FP) in the former (57/99) and its absence in the later (0/80). In the population
      operated on microsurgically, the presence of a permanent FP (57 patients among 99
      responding to the questionnaire) was, of course, associated with a high rate of
      complaint, with burning eye in 27 and crying eye in 39. In patients from the two
      arms with no FP, a dry eye was reported in 8/64 after GKS and 7/42 after MS (not
      significant) and a burning eye in 9/64 after GKS and 9/42 after MS (not
      significant). Thus, 14% of patients with no clinical signs of impairment of the
      VIIth motor nerve presented signs indicating the injury of the intermedius nerve,
      with the same probability whatever the kind of surgery. When no permanent FP was
      observed, a crocodile tear syndrome was more frequently observed after MS (4/42
      versus 1/64; p = 0.07). This suggests an early lesion of the VIIth motor nerve
      and nervus intermedius and a subsequent abnormal regrowth. The only patient
      reporting a crocodile tear syndrome after GKS turned out to have a transiently
      presented mild deficit of the orbicular muscle signing a transient partial facial
      nerve injury. In the absence of FP, a 'crying eye' was reported more frequently
      after MS (16/42 vs. 9/64; p = 0.01) leading us to suspect a frequent subclinical
      injury of the VIIth nerve in those patients operated on using MS with no obvious
      FP. Patients tested with the Schirmer test before and more than 2 years later
      were improved in 27.3%, stable in 56.1% and worse in 16.7% of cases. The answers
      about taste showed that 8.1% of patients after GKS and 45.5% of patients after MS
      complained of taste. CONCLUSIONS: This study is the first demonstrating that RS
      can induce nervus intermedius injury in a small percentage of cases (14%). These
      patients have been treated 11 years ago with what we can consider as 'archeo-GKS
      technology' compared to today's radiosurgical instruments. Influence of modern
      GKS on the nervus intermedius is currently under evaluation in our group.
      However, symptoms related to the eye and taste either due to the injury of the
      nervus intermedius or the VIIth motor nerve or both are much more frequent after
      MS than after RS.

PMID- 18810209
TI  - Surgical treatment of facial nerve schwannomas.
AB  - Facial nerve schwannomas are rare. They occur all along the nerve's course from
      the cerebellopontine angle to the parotid region. Clinically, intracranial facial
      nerve schwannomas often present with facial nerve paralysis or hearing loss and
      may initially be misdiagnosed as vestibular schwannomas. Modern imaging
      techniques allow diagnosis and evaluate tumor location, size and extension.
      Functional tests evaluate facial nerve and hearing function. All this information
      results in an individual management plan. Microsurgery, stereotactic radiosurgery
      and observation are the therapeutic options. Surgery is planned depending on
      tumor features and the preoperative functional status. Subtemporal, transmastoid,
      translabyrinthine and retrosigmoid approaches are the principal routes.
      Preservation of facial nerve function is the main surgical difficulty. Anatomical
      nerve conservation, nerve resection with immediate grafting or delayed hypoglosso
      facial nerve anastomosis are possible. The main predicting factors of
      postoperative facial function are the degree and duration of facial paralysis
      before surgery. Observation is an option for small tumors and asymptomatic
      patients. In these cases, a close follow-up is mandatory. The optimal timing for
      surgery is critical: waiting maximizes the time with good facial function, but
      increases the risk of hearing loss by cochlea erosion and lowers the chances of
      postoperative facial nerve recovery once paralysis has occurred. The role of
      radiosurgery is still to be determined: it seems suitable for inoperable patients
      and recurrent tumors.

PMID- 18810210
TI  - Gamma knife surgery for facial nerve schwannomas.
AB  - Radical resection of facial nerve schwannomas classically implies a high risk of
      severe facial palsy. Due to the rarity of facial palsy following Gamma Knife
      surgery (GKS) of vestibular schwannomas, functional evaluation after GKS in this
      specific group of patient appears rational. Clinical management due to the
      specificity and heterogeneity of this group of patients has required the
      development of an original classification of 4 anatomical subtypes presenting
      different clinical and surgical difficulties. Among 1,783 schwannomas of the
      cerebellopontine angle treated by GKS in Timone University Hospital between July
      1992 and May 2003, 11 were diagnosed as originating from the facial nerve.
      Criteria for this diagnosis were: the involvement of the tympanic or mastoid
      segment of the facial nerve (9 patients); and/or preoperative observation of a
      facial nerve deficit that had occurred during previous microsurgery (2 patients).
      The rare occurrence of facial palsy after vestibular schwannoma radiosurgery,
      usually occurring within 18 months of treatment, has been considered only in the
      patients with more than 2 years of follow-up (9 patients). At last follow-up
      examination, no patients had developed a new facial palsy or experienced
      deterioration of a pre-existing facial palsy; 3 patients had improvement of a
      preoperative facial palsy. Ten of 11 tumors were stable, or decreased in size; in
      the remaining case, microsurgical resection of the tumor had been recommended due
      to the development of a cyst. This first study demonstrates that radiosurgery
      allows treatment of these patients while preserving normal motor facial function.
      Such an advantage should lead to the consideration of GKS as a first treatment
      option for small- to middle-sized facial nerve schwannomas.

PMID- 18810211
TI  - Hearing preservation after complete microsurgical removal in vestibular
      schwannomas.
AB  - AIM: To evaluate and present the treatment strategy and hearing preservation in a
      recent series of vestibular schwannoma cases. MATERIALS AND METHODS: A
      retrospective analysis of 200 patients operated consecutively over a 3 year
      period was performed. Patient records, operative reports, including data from the
      electrophysiological monitoring, follow-up audiometric examinations, and
      neuroradiological findings were analyzed. RESULTS: The anatomical integrity of
      the cochlear nerve was preserved in 75.8% of the cases. When only patients with
      preserved preoperative hearing were included, the rate was 84%. The overall rate
      of functional hearing preservation was 51%. It was highest in small tumors--60%
      in class T1 and 72% in class T2. In tumors extending to and compressing the brain
      stem, preservation of some hearing was possible in up to 43%. CONCLUSIONS:
      Vestibular schwannomas are benign lesions whose total removal leads to definitive
      healing of the patient. The goal of every surgery should be functional
      preservation of all cranial nerves. Using the retrosigmoid approach with the
      patient in the semi-sitting position, hearing preservation is possible even for
      large schwannomas.

PMID- 18810212
TI  - Hearing preservation in patients with unilateral vestibular schwannoma after
      gamma knife surgery.
AB  - INTRODUCTION: The majority of patients still lose the functionality of their
      hearing in spite of the technical advances in microsurgery. Our aim was to
      evaluate the hearing preservation potential of Gamma Knife Surgery. We have
      reviewed our experience and the literature in order to evaluate the probability
      to obtain such functional preservation and the factors influencing it. METHODS:
      Since July 1992, 2,053 patients have been operated on by Gamma Knife Radiosurgery
      in Timone University Hospital. This population included 184 unilateral schwannoma
      patients with functional preoperative hearing (Gardner-Robertson 1 or 2) treated
      by first intention radiosurgery with a marginal dose lower than 13 Gy. The
      population included 74 patients with subnormal hearing (class 1). All have been
      studied with a follow-up longer than 3 years. Univariate and multivariate
      analyses have been carried out. RESULTS: Numerous parameters greatly influence
      the probability of functional hearing preservation at 3 years, which is globally
      60%. The main preoperative parameters of predictability are limited hearing loss
      that is Gardner-Robertson stage 1 (vs. 2), presence of tinnitus, young age of the
      patient and small size of the lesion. The functional hearing preservation at 3
      years is 77.8% when the patient is initially in stage 1, 80% in patients with
      tinnitus as a first symptom and 95% when the patient has both. In these patients,
      the probability of functional preservation at 5 years is 84%. Comparison of these
      results with the main series of the literature confirms the reproducibility of
      our results. Additionally, we have demonstrated a higher chance of hearing
      preservation when the dose to the cochlea is lower than 4 Gy. CONCLUSION: We
      report a large population of patients treated by radiosurgery with functional
      preoperative hearing. These results demonstrate the possibility to preserve
      functional hearing in a high percentage of selected patients. Radiosurgery offers
      them a higher chance of functional hearing preservation than microsurgery or
      simple follow-up.

PMID- 18810213
TI  - Surgical removal of vestibular schwannoma after failed gamma knife radiosurgery.
AB  - One of the main criticisms of vestibular schwannoma (VS) radiosurgery is that the
      risk of surgical morbidity is increased for patients whose tumor progresses in
      cases of failed procedures. The authors reviewed the French neurosurgical
      experience of operated patients after failed Gamma Knife radiosurgery (GKR). From
      July 1992 to December 2000, 23 unilateral VS out of the 1,000 treated patients
      have undergone a microsurgical procedure after failed GKR. In order to analyze
      the difficulties observed during the surgery, a questionnaire was completed by
      the surgeons. The mean interval between radiosurgery and removal was 39 months
      (range: 10-92 months). The mean increasing volume was 389% (range: 37-1,600) and
      the median was 150%. Seven patients have been operated on for radiological tumor
      growth and 13 for clinicoradiological evolution. In 10 cases, the surgeon
      considered that he had to face unusual difficulties mainly because of adhesion of
      the tumor to neurovascular structures. Tumor removal was total in 15 cases, near
      total in 4 cases and subtotal in 4 cases. One case of venous infarction was
      noticed on the 2nd day following surgery and was responsible for hemiparesis and
      aphasia that gradually recovered. At the last follow-up examination, facial nerve
      was normal or near normal (House-Brackmann grades 1 and 2) in 12 cases (52%)
      while it was grade 3 in 9 cases and grades 4 and 5 in 2 cases. Our results show
      that the quality of removal and of facial nerve preservation might be impaired
      after GKR in half of cases. However, these results do not support a change in our
      policy of first intention radiosurgical treatment of small- to medium-sized VSs.

PMID- 18810214
TI  - Microsurgical removal of vestibular schwannomas after failed previous
      microsurgery.
AB  - Recurrent and regrowing large vestibular schwannomas (VSs) may require another
      microsurgical procedure. Little is known about the incidence and the consequences
      of this second surgical procedure. We reviewed our own 10 reoperated cases during
      a 20-year period. Eight of them were supposed to have a radical surgery at the
      initial step, while 2 had experienced a subtotal resection. The mean interval
      between the 2 surgeries was 8.3 years with an ultra-late recurrent case at 20
      years. Additional surgery was justified by a large-sized growing tumor in main
      cases and/or occurrence of new symptoms. We used a widened translabyrinthine
      approach in 9 cases and a retrosigmoid route in 1 case. Preservation of a good
      facial nerve motion (H-B gd I or II) was obtained in 3 out of the 6 cases who
      displayed this preoperative status. Excluding the facial nerve injury, no major
      complication was observed in these cases. These results confirm that the
      iterative surgical procedure for VS carries additional difficulties with respect
      to functional preservation. Assuming that radiosurgery is an effective tool to
      control small- to middle-sized VSs, priority was recently given to the facial
      nerve preservation during the surgical removal of recurrent and regrowing VSs.

PMID- 18810215
TI  - Vestibular schwannoma radiosurgery after previous surgical resection or
      stereotactic radiosurgery.
AB  - OBJECTIVE: To evaluate radiosurgery outcomes in vestibular schwannoma (VS)
      patients who have undergone prior tumor treatment. METHODS: Retrospective review
      of 55 consecutive VS patients having radiosurgery for recurrent (n = 22) or
      residual tumors (n = 33) after prior microsurgery. The median time from the
      patients' last surgery was 60 months (range, 2-463). Forty-seven patients (84%)
      had enlarging tumors at the time of radiosurgery. RESULTS: The majority of
      patients (67%) had facial weakness prior to radiosurgery; 52 patients (95%) were
      deaf. The median tumor volume was 3.0 cm3 (range, 0.1-18.1). The median tumor
      margin dose was 14 Gy (range, 12-20). Fifty patients had follow-up available at a
      median of 47 months (range, 5-148) after radiosurgery. The tumor control rate was
      94%. Trigeminal deficits developed in 2 patients (4%). Four of 42 patients (10%)
      with normal to moderate facial nerve function before radiosurgery developed
      facial weakness. Three of these 4 patients received a tumor margin dose of 20 Gy.
      CONCLUSION: Radiosurgery is effective for patients with recurrent or residual VSs
      after prior surgical removal. Repeat radiosurgery after initial failed
      radiosurgery can be considered, but little information is available to evaluate
      this approach. Staged treatment involving subtotal tumor removal and radiosurgery
      is an option for patients with large VSs to facilitate both cranial nerve
      preservation and long-term tumor control.

PMID- 18810216
TI  - Microsurgery management of vestibular schwannomas in neurofibromatosis type 2:
      indications and results.
AB  - AIM: To analyze the senior author's experience and strategy of treatment of
      patients with neurofibromatosis type 2 (NF2), with particular emphasis on
      vestibular schwannoma (VS) surgery. MATERIALS AND METHODS: Over a period of more
      than 35 years, the senior author (M.S.) has operated on more than 165 patients
      with NF2. The total number of VS surgeries was 210. This retrospective analysis
      includes 145 consecutively operated patients. Medical records, operative reports,
      follow-up neurological, audiometric examinations, and neuroradiological findings
      were analyzed. RESULTS: Total tumor removal was achieved in 85% of the operated
      tumors. In 15%, deliberately subtotal removal was performed for brain stem
      decompression and hearing preservation in the only hearing ear. The overall rate
      of hearing preservation was 35%. When only patients with preserved useful
      preoperative hearing were included, the rate was 65%. Bilateral hearing after
      surgery was preserved in 23% of the patients. The anatomical integrity of the
      facial nerve was preserved in 89%. CONCLUSIONS: The goal of VS surgery in
      patients with NF2 should be complete removal but not at the expense of functional
      impairment. Carefully individualized treatment strategy offers the possibility of
      prolongation of life and preservation of neurological functions.

PMID- 18810217
TI  - Radiosurgery for type II neurofibromatosis.
AB  - A summary of our radiosurgical experience treating type II neurofibromatosis
      (NF2) vestibular schwannomas (VSs), based on a retrospective consecutive series
      of 122 tumours in 92 patients, with an extended series of a further 22 patients
      (906 patient-years of follow-up) to investigate the risk of malignancy after
      radiosurgery. With current techniques, we estimate that 8 years after
      radiosurgery for NF2 VS, 20% of patients will have required further treatment,
      50% will be well controlled, and in 30% there will have been some concern about
      control, but they will have been managed conservatively. Three years after
      treatment, approximately 40% retain their functional hearing, 40% have some
      deterioration, 20% becoming deaf in that ear. The risk of facial palsy was 5%.
      Two malignancies were recorded after radiosurgery, in one the malignant behaviour
      preceded treatment. This is less than the previously reported rate of
      spontaneously developing malignant gliomas in NF2. Whilst the clinical results
      are far worse than those achieved treating sporadic tumours, this applies equally
      to the results of surgery or observation when treating NF2 tumours. It is
      important therefore that these patients are given advice specific for NF2.
      Considering this, we believe that radiosurgery remains a valuable minimally
      invasive treatment option for selected NF2 patients.

PMID- 18810218
TI  - Microsurgical treatment of intracanalicular vestibular schwannomas.
AB  - Early treatment of intracanalicular vestibular schwannomas (IVSs) may be
      advisable because their spontaneous course will show hearing loss in most cases.
      Advanced microsurgical techniques and continuous intraoperative monitoring of
      cranial nerves may allow hearing preservation (HP) without facial nerve damage.
      However, there are still controversies about the definition of HP and the best
      surgical approach that should be used. In this study, we reviewed the main data
      from the recent literature on IVS surgery and compared hearing, facial function
      and complication rates after the retrosigmoid and middle fossa approaches,
      respectively. The results showed that the average HP rate is approximately 45%
      after IVS surgery whatever the surgical route. HP varied widely depending on the
      audiometric criteria that were used for definition of serviceable hearing. There
      was a trend to show that middle fossa approach offered a better quality of
      postoperative hearing (not statistically significant), whereas the retrosigmoid
      approach offered a better facial nerve preservation and fewer complications (not
      statistically significant). We believe that the timing of treatment in the course
      of the disease and selection between radiosurgical versus microsurgical procedure
      are key issues in the management of IVS. Once open surgery has been decided,
      selection of the approach mainly depends on individual anatomical considerations
      and experience of the surgeon.

PMID- 18810219
TI  - Radiosurgery for intracanalicular vestibular schwannomas.
AB  - Advances in central nervous system imaging have resulted in early detection of a
      greater number of intracanalicular vestibular schwannomas. Early detection of
      intracanalicular vestibular schwannomas raises the issue of whether or not
      treatment is required and, if so, whether radiosurgery is the most appropriate
      option. Available evidence indicates that a majority of intracanalicular lesions
      are observed to grow and most will be associated with progressive hearing loss
      or, less frequently, sudden persistent hearing loss. If the objective of
      treatment is to preserve serviceable binaural hearing, early intervention is
      advisable. Early intervention is advantageous only if serviceable hearing can be
      maintained in the majority of patients along with low perioperative morbidity.
      Radiosurgery seems to achieve these goals ideally. Radiosurgery is a minimally
      invasive management option for patients with intracanalicular tumors.
      Radiosurgery provides high rate of long-term hearing preservation with minimal
      morbidity.

PMID- 18810220
TI  - Hydrocephalus and vestibular schwannomas: considerations about the impact of
      gamma knife radiosurgery.
AB  - Hydrocephalus may occur at various stages of the natural course of vestibular
      schwannoma and can also be diagnosed after the therapeutic procedure. The aim of
      the present study was to analyze the impact of Gamma Knife radiosurgery (GKR) on
      previously diagnosed hydrocephalus (group A patients) and to evaluate the
      incidence of de novo hydrocephalus after GKR (group B patients). We reviewed
      retrospectively our case material and the data from the literature. Among the
      first 1,000 vestibular schwannoma patients treated by GKR in our institution, 30
      patients (3%) belonged to group A and 1% to group B. In both groups,
      hydrocephalus was more often associated with the following data: Elderly, large
      tumor, previous MS, NF2 disease and bilateral tumors. Cerebrospinal fluid (CSF)
      shunting system was needed in 25% of the group A and in all of the group B
      patients. In this latter group, CSF shunting was justified by poor clinical
      tolerance, and the mean interval between GKR and CSF shunting was 14.8 months
      (range: 4-31 months). These data suggest that GKR does not decompensate the
      majority of preexisting radiological hydrocephalus. De novo post-GKR
      hydrocephalus is of low incidence, comparable to the postoperative rate.
      Generally, it comes early after GKR and justifies CSF shunting. Thus, it may be
      postulated that in a small subgroup of patients, GKR may disturb the normal
      hydrodynamic pathway. Mechanisms of such event remain controversial.

PMID- 18810221
TI  - Radiosurgery and carcinogenesis risk.
AB  - The definition of radiation-induced tumors is based on indirect criteria. They
      were defined initially by Cahan: the tumors must occur at the irradiated site
      after a time of latency longer than 5 years and be of a different pathological
      type from the initially irradiated tumor. The central nervous system belongs to
      sensitive tissue and it seems that a threshold dose does not exist. Thus, the
      relative risk varies from 1.57 to 8.75 for a dose of 1 Gy. It increases with the
      time of observation with a maximum of 18.4 between 20 and 25 years. Thus the
      cerebral radiation-induced tumors would be dependent on low dose for large
      volumes of healthy cerebral tissue (tineas, acute leukemia), and high dose for
      small volumes as irradiated benign lesions (pituitary tumors, meningiomas).
      Several factors influence the incidence of these radiation-induced tumors, of
      which the age at exposure and individual susceptibility are related to heredity.
      To date, 3 cases of radio-associated glioblastoma and 5 cases of transformed
      vestibular schwannoma related to radiosurgery were reported in the literature.
      They do not present all the traditional criteria. Thus, we reported through our
      experience 2 cases illustrating these problems to confront them with the
      published data. The long-term risk of radiation-induced tumor requires a time of
      observation between 5 and 30 years. This risk is estimated at less than 1 per
      1,000. It must be communicated to each patient and counterbalanced with the
      operational risk of a benign tumor (1 per 100 of perioperative mortality) or the
      hemorrhagic risk of an untreated arteriovenous malformation (1 per 100 per year).

PMID- 18810222
TI  - Vestibular schwannomas: complications of microsurgery.
AB  - Current microsurgical treatment of vestibular schwannomas usually brings
      satisfactory results for the patients. However, transient or permanent
      complications may occur, especially when treating large tumors. Precise
      information about these potential complications has to be given to the patient at
      the time of the surgical decision. Based on their personal experience of large
      operated vestibular schwannomas and analyzing a review of the international
      literature, the authors detail these complications and the way to prevent and
      manage them. The problems that are linked to the variety of surgical approaches
      are also commented. The most frequent complication is cerebrospinal fluid leak
      that requires medical management and in less than one third of cases, surgical
      exploration. Vascular problems including ischemia or hemorrhage inside the
      posterior fossa represent the main source of permanent morbidity. Lower cranial
      nerve deficits are unusual but may expose to early and delayed aspiration
      pneumonias. The authors conclude that careful selection of cases, meticulous
      operative management and intensive postoperative care are essential steps to
      prevent and to treat these complications.

PMID- 18810223
TI  - Vestibular schwannoma management: an evidence-based comparison of stereotactic
      radiosurgery and microsurgical resection.
AB  - BACKGROUND: The best management of vestibular schwannoma (VS) patients is
      controversial. METHODS: A comparison of surgical resection and stereotactic
      radiosurgery based on recent studies using evidence-based medicine standards.
      Level 1 evidence is derived from randomized clinical trials, whereas levels 2, 3,
      4, and 5 refer to prospective cohort studies, case-control series, case series,
      and expert opinions, respectively. RESULTS: The vast majority of studies on VS
      management are either retrospective case series or opinions (level 4 and 5
      evidence). Five retrospective case-control series (level 3 evidence) have shown
      improved cranial nerve outcomes, better cost effectiveness, and less impact on
      patients' activities of daily living for patients having radiosurgery. One
      prospective cohort study (level 2 evidence) found outcomes were superior for
      patients having radiosurgery compared to surgical resection with regard to facial
      movement, hearing preservation and quality of life measures. No randomized
      clinical trial has been performed to compare these two techniques. CONCLUSION:
      The best quality of evidence (levels 2 and 3) show superior outcomes for VS
      patients having stereotactic radiosurgery compared to surgical resection allowing
      a grade B recommendation for this approach. Unless long-term follow-up shows
      frequent tumor progression at currently used radiation doses, radiosurgery should
      be considered the best management strategy for the majority of VS patients.

PMID- 18810224
TI  - Linear accelerator radiosurgery for vestibular schwannomas.
AB  - Linear accelerator (LINAC) radiosurgery was developed in the 1980s. The treatment
      paradigm uses the rotating high-energy X-ray output of the LINAC to focus many
      hundreds of 'beam equivalents' on intracranial or spinal targets. At the
      University of Florida, 450 vestibular schwannomas have been treated. Tumor
      control has been achieved in 90% (5- year actuarial data). 99% of patients
      treated have required no further intervention. Since reducing the treatment dose
      to 1,250 cGy, in 1994, the incidence of facial and trigeminal nerve injury has
      been <1%. No instance of malignant tumor transformation has been observed. Other
      institutions using modern LINAC techniques report similar excellent results. We
      believe that radiosurgery is the treatment of choice for smaller vestibular
      schwannomas.

PMID- 18810225
TI  - Radiotherapy of cranial nerve schwannomas.
AB  - Fractionated stereotactic radiotherapy is an attractive, low-morbidity
      alternative to surgical resection for managing cranial nerve schwannomas. So far,
      the outcomes reported from fractionated stereotactic radiotherapy seem roughly
      equivalent to contemporary radiosurgery series. However, a randomized, controlled
      clinical trial is needed to adequately compare these techniques.

PMID- 18810226
TI  - Future perspectives in acoustic neuroma management.
AB  - Management options for patients with vestibular schwannomas (acoustic neuromas)
      include observation, resection, stereotactic radiosurgery, or fractionated
      radiotherapy. In this report, we review our experience with radiosurgery over a
      20-year interval, and discuss indications and expectations with the different
      approaches. There has been an evolution in available technologies, and an
      evolution in both patient and physician approaches to the management of this
      tumor. Patient decisions must be based on quality information from the peer
      reviewed literature. Future concepts for radiosurgery are discussed.

PMID- 18810228
TI  - Evidence for internal filtration in the Genius system, performing slow low
      efficient daily dialysis in the intensive care unit.
AB  - BACKGROUND: Since most intensive care units (ICUs) have no access to high-quality
      water, the Genius system, using ultrapure water and high-flux dialyzers, might be
      used during slow low efficient daily dialysis (SLEDD). To get an idea about
      convective removal, internal filtration (IF) was calculated and compared to other
      modalities. METHODS: Validated with in vivo measurements, IF was calculated for 8
      h Genius SLEDD and 4 h Genius standard dialysis with high-flux dialyzers, and for
      8 h SLEDD and 4 h both with standard dialysis machines and low-flux as well as
      high-flux dialyzers. RESULTS: In Genius SLEDD (FX80), IF was 2.36 l (hematocrit
      [Hct] 30%) and 3.37 l (Hct 40%). About the same amount of IF was found for the
      different dialysis modalities, except when using low-flux dialyzers, where no IF
      occurred. CONCLUSION: The Genius system allows the implementation of high-flux
      dialysis with ultrapure dialysate, and can be run in a SLEDD mode in the ICU.

PMID- 18810227
TI  - Acute kidney injury after transarterial chemoembolization for hepatocellular
      carcinoma: a retrospective analysis.
AB  - BACKGROUND: Transarterial chemoembolization (TACE) for hepatocellular carcinoma
      (HCC) may result in acute kidney injury (AKI) like other angiographic
      interventions. METHODS: To investigate the incidence, risk factor and outcomes of
      AKI after TACE, defined by Acute Kidney Injury Network (AKIN) criteria, we
      retrospectively analyzed 442 TACE treatment sessions in 236 HCC patients.
      RESULTS: The incidence of AKI in the first 48 h after TACE was 9.8% (23 of 236
      patients at risk). Presence of hypertension (OR 3.24, 95% CI 1.21-8.72, p =
      0.02), lower baseline serum albumin (OR 0.29, 95% CI 0.15-0.56, p < 0.01) and
      higher creatinine level (OR 12.02, 95% CI 3.49-41.39, p < 0.01) were independent
      risk factors of AKI. Prolonged renal insufficiency after 1 month was observed in
      24.1% of AKI episodes. CONCLUSION: AKI is a common complication after TACE and we
      have to pay attention to the prevention and early recognition of AKI occurrence
      in high-risk patients.

PMID- 18810229
TI  - Physiologic variability of vascular access blood flow for hemodialysis.
AB  - AIM: To assess the variability of blood flow (QVA) through a native arteriovenous
      fistula (AVF) in the long-term and to determine the QVA reduction at which an
      intervention is appropriate. PATIENTS AND METHODS: The study was performed in a
      group of 34 chronic hemodialysis patients with no history of a AVF intervention.
      QVA was measured using the thermodilution method (Blood Thermodilution Monitor,
      Fresenius). Median follow-up was 41 months and the median number of QVA
      measurements in each patient was 15. The coefficient of variation (CV) of QVA was
      calculated for each patient. RESULTS: Mean QVA was 904 +/- 334 ml/min. The mean
      CV was 23.3 +/- 11.2%. CONCLUSION: QVA may fluctuate during a long-term follow-up
      period. The detection of QVA decrease by 20-25% could be still within
      physiological limits. Based on the results we recommend to first repeat the
      measurement at a shorter interval and to refer the patient to a radiologist only
      when the decreasing trend is confirmed.

PMID- 18810230
TI  - When should renal replacement therapy for acute kidney injury be initiated and
      discontinued?
AB  - BACKGROUND: Critically ill patients with acute kidney injury (AKI) are at high
      risk for death and frequently require initiation of renal replacement therapy
      (RRT). There is wide variation in clinical practice on the indications for and
      timing of initiation and discontinuation of RRT. Numerous clinical and
      biochemical factors (i.e. uremic, metabolic, fluid balance) have been used;
      however, at present there is no consensus to guide clinicians on the most
      favorable time to initiate and/or discontinue RRT to optimize patient outcomes.
      METHODS: In this review, we appraise the available clinical studies that have
      assessed timing of initiation and/or discontinuation of RRT for critically ill
      patients with AKI. 'Timing' of initiation has been variably defined including use
      of conventional biomarkers (i.e. serum urea and creatinine), urine output, fluid
      balance, and time relative to intensive care unit admission. CONCLUSIONS:
      Numerous studies consistently point toward a survival benefit to early initiation
      of RRT; however, there is a paucity of high-quality randomized trials. If early
      RRT is associated with clinical benefit, it remains uncertain whether this is
      attributable to more rapid metabolic/uremic control, management of fluid balance
      or a combination of clinical factors. In addition, timing of RRT initiation is
      likely context-specific and varies by clinical factors and/or etiology of AKI.
      There is also little data to accurately distinguish in advance between the
      injured kidney that will need extracorporeal renal support and one that retains
      capacity for early recovery. Fewer studies have evaluated the process of weaning
      of RRT or ideal methods to predict sufficient recovery to avoid re-initiation.
      Longer duration of RRT support, higher illness severity and lower urine output
      (independent of diuretic therapy) have all predicted need for re-initiation.
      Additional investigations on these issues are clearly warranted and urgently
      needed.

PMID- 18810231
TI  - Cerebral vasculitis and stroke in Lyme neuroborreliosis. Two case reports and
      review of current knowledge.
AB  - We report on 2 patients with cerebral vasculitis and stroke due to Lyme
      neuroborreliosis (LNB). Both patients had a prodromal stage involving headaches,
      and showed meningeal enhancement in addition to ischemic infarctions on brain
      magnetic resonance imaging and diffuse vasculitis on vascular imaging.
      Serological and cerebrospinal (CSF) fluid studies confirmed the diagnosis of
      active LNB. Ceftriaxone for 3 weeks led to an excellent recovery and improvements
      in the CSF examination findings. Stroke physicians should be aware of this rare
      presentation of LNB. A review of the current knowledge on cerebral vasculitis due
      to LNB is provided.

PMID- 18810233
TI  - Economic evaluation alongside a phase II, multi-centre, randomised controlled
      trial of very early rehabilitation after stroke (AVERT).
AB  - BACKGROUND/PURPOSE: The effectiveness and costs of very early rehabilitation
      after stroke are unknown. This study assessed the cost effectiveness of very
      early mobilisation in addition to standard care (VEM) compared with standard care
      alone (SC). METHODS: Cost-effectiveness analysis alongside a phase II, multi
      centre, randomised controlled trial (RCT) with blinded outcome assessments. Less
      than 24 h after stroke, patients were recruited from two stroke units and
      randomised to receive VEM or SC. The intervention continued until discharge or 14
      days, whichever was sooner. The efficacy measure was a dichotomised modified
      Rankin Scale (mRS) at 3 months with mRS < or =2 representing good outcome. Costs
      were determined from medical records and patient interviews at 3, 6 and 12
      months. National average (where available) or local costs were applied for the
      reference year 2004. Differences in mean total costs at 3 and 12 months were
      tested using t test assuming unequal variances. An incremental cost-effectiveness
      ratio was calculated and probabilistic uncertainty analysis was undertaken.
      RESULTS: The sample consisted of 38 VEM and 33 SC patients. A trend for good
      outcome with VEM compared to SC was found (adjusted OR 4.10, 95% CI 0.99-16.88, p
      = 0.051). Patients receiving VEM incurred significantly less costs at 3 months
      (AUD 13,559) compared with SC (AUD 21,860; p = 0.02). This difference in mean per
      patient total cost persisted at the 12-month assessment (VEM: AUD 17,564; SC: AUD
      29,750; p = 0.03). VEM was found to be a 'dominant' (more effective, less cost)
      intervention when compared to SC at 3 months. CONCLUSION: These findings provide
      preliminary evidence that VEM is likely to be cost-effective. A large RCT is
      currently underway to confirm the cost effectiveness of VEM.

PMID- 18810232
TI  - Sex differences in stroke.
AB  - Increasing evidence suggests that sex differences exist in the etiology,
      presentation, treatment, and outcome from stroke. The reasons for these sex
      disparities are becoming increasingly explored, but large gaps still exist in our
      knowledge. Experimental studies over the past several years have demonstrated
      intrinsic sex differences both in vivo and in animal models which may have
      relevance to our understanding of stroke in clinical populations. A greater
      understanding of the differences and similarities between males and females with
      respect to the risk factors, pathophysiology, and response to stroke will
      facilitate the design of future clinical trials and enhance the development of
      treatment strategies to improve stroke care in both sexes. This article reviews
      the current literature on sex differences in stroke with an emphasis on the
      clinical data, incorporating an analysis of bench research as it pertains to the
      bedside.

PMID- 18810234
TI  - Assessment of feasibility of endovascular treatment of ruptured intracranial
      aneurysms with 16-detector row CT angiography.
AB  - BACKGROUND: It is unclear whether 16-detector row CT angiography (CTA) can
      replace digital subtraction angiography (DSA) to assess the feasibility of
      endovascular treatment (EVT) in the acute phase after aneurysmal subarachnoid
      hemorrhage. METHODS: We studied 80 consecutive patients with aneurysmal
      subarachnoid hemorrhage, who underwent both CTA and DSA. Two interventional
      neuroradiologists independently scored CTA and, immediately thereafter, DSA with
      respect to feasibility of EVT. We determined whether CTA without DSA was
      sufficient for a definite judgment. We also assessed interobserver agreement.
      RESULTS: The 2 readers judged EVT to be feasible in 24 and 37 patients with CTA
      alone and not feasible in 34 and 20 patients. In these patients, DSA yielded
      additional information in 6 (reader 1) and 5 patients (reader 2), which did not
      affect treatment decision. In 19 and 7 patients, DSA was considered inferior to
      CTA. In the remaining patients (n = 22 and 23, respectively), feasibility of EVT
      could not be judged with CTA alone, and DSA results were required in addition for
      a treatment decision. Interobserver agreement on feasibility of EVT was just fair
      (kappa <0.40). CONCLUSIONS: In our series of patients, 16-detector row CTA was a
      reliable investigation to assess feasibility of EVT of ruptured intracranial
      aneurysms in most patients. Further, we found that interobserver disagreement on
      feasibility of EVT was considerable.

PMID- 18810235
TI  - Prognosis of symptomatic and asymptomatic middle cerebral artery occlusion.
AB  - BACKGROUND: The annual risk of stroke or cardiovascular events has been reported
      to be over 10% in middle cerebral artery stenosis. However, the prognosis of
      patients with middle cerebral artery occlusion (MCAO) remains unclear. We
      investigated the risk of cardiovascular events or death in patients with
      symptomatic or asymptomatic MCAO. METHODS: Consecutive patients with MCAO
      demonstrated by transcranial Doppler sonography and magnetic resonance
      angiography were enrolled. Medical records were reviewed during the follow-up
      period and a telephone interview was conducted using a preformed questionnaire,
      comparing asymptomatic and symptomatic patients who had a history of ischemic
      stroke or transient ischemic attack in the same vascular territory. The composite
      outcome of ipsilateral stroke, hemorrhagic stroke, overall stroke, myocardial
      infarction (MI), any vascular death and nonvascular death was evaluated during
      the follow-up period. RESULTS: Thirty-seven of the 48 patients were symptomatic
      and 11 were asymptomatic. During the mean follow-up period of 2.8 years,
      cardiovascular events or death occurred in a total of 13 patients: 1 from the
      asymptomatic group and 12 from the symptomatic group (overall stroke, 6; MI, 2;
      vascular death, 1; nonvascular death, 5). The annual rates of composite outcome
      (2.2 vs. 13.2%, p = 0.041) and overall stroke (0.0 vs. 6.6%, p = 0.048) were
      significantly lower in the asymptomatic group. CONCLUSION: These results suggest
      that the overall prognosis of MCAO is not worse than previously reported for
      patients with middle cerebral artery stenosis or internal carotid artery
      stenosis. Asymptomatic MCAO seems to be a benign condition associated with a low
      risk of subsequent stroke, MI or death under the optimal medical therapy.

PMID- 18810236
TI  - Predictors of carotid clamping intolerance during endarterectomy that would be
      wise to apply to stenting procedures.
AB  - BACKGROUND AND PURPOSE: Carotid artery stenting procedures are increasingly being
      performed with devices such as the MO.MA or the Parodi system that involve
      endovascular clamping of the common carotid artery, thus exposing the ipsilateral
      hemisphere to the risk of hypoperfusion. The aim of the present study was to look
      for predictors of carotid clamping intolerance by means of transcranial Doppler.
      PATIENTS AND METHODS: We analysed the findings of an earlier Italian multicentre
      prospective study (SCITEA, Italian Cooperative Study of Transcranial Doppler in
      Carotid Endarterectomy) in which 513 consecutive patients (males/females 397/116,
      mean age 67 +/- 7 years, mean carotid stenosis 81 +/- 11%, NASCET method)
      scheduled to undergo carotid endarterectomy had been investigated non-invasively
      with transcranial Doppler, and we correlated the data obtained preoperatively
      with the need to insert a shunt during surgery as an index of intolerance to
      carotid clamping. RESULTS: Four hundred and thirty-nine patients (85.6%)
      underwent surgery without and 74 (14.4%) with the insertion of a shunt. Patients
      who needed a shunt (intolerant) had a significantly higher decrement in mean flow
      velocity in the ipsilateral middle cerebral artery (MCA) after compression of the
      ipsilateral common carotid artery (71.8 +/- 22 vs. 30.6 +/- 24%) and were
      significantly more likely to have non-recruitable collateral pathways (75 vs.
      18%). Logistic regression analysis confirmed that an MCA decrement of >85% (p =
      0.005) and no potential collateralization (p = 0.011) were independent predictors
      of clamping intolerance. Combining the results of both compression tests (MCA
      decrement and collateral recruitment) yielded a sensitivity of 64%, a specificity
      of 99%, a positive predicted value of 88%, a negative predicted value of 95% and
      an overall accuracy of 95% in predicting shunt insertion. CONCLUSIONS: The
      preoperative assessment of recruitable collaterals and of maximal decrement in
      MCA mean flow velocity after carotid compression are useful predictors of carotid
      clamping intolerance. The criteria derived from carotid endarterectomy need to be
      applied and validated in a prospective series of patients undergoing carotid
      artery stenting procedures.

PMID- 18810237
TI  - Spinal cord infarction in Chinese patients. Clinical features, risk factors,
      imaging and prognosis.
AB  - BACKGROUND: The clinical presentations, MRI findings and outcomes for spinal cord
      infarction (SCI) are well documented in the West but scarce in the East. We
      investigated the clinical characteristics of SCI patients and further analyzed
      etiologies and prognostic factors in Chinese subjects. METHODS: We reviewed all
      SCI patients from March 1993 to March 2007. Clinical symptoms, laboratory and
      imaging findings as well as outcomes were retrospectively analyzed. RESULTS:
      Twenty-two patients (12 female) were identified; their mean age was 57.6 years.
      Nine patients (40.9%) had probable etiologies, while 13 were cryptogenic (59.1%).
      The primary etiologies were aortic diseases. Hypertension was the most common
      vascular risk factor (50%). Most patients (10/22 = 45.5%) had thoracolumbar
      lesions (mainly at T(9)-L(1)), while cervical lesions (9/22 = 40.9%) were the
      second most common (mainly at C(4)-C(7)). 'Owl's eyes' signs were common with the
      anterior spinal artery (93.8%) and central cord infarctions (50%) but not in the
      posterior spinal artery or transverse spinal infarctions. After a mean follow-up
      of 18 months, only 10 patients (10/22 = 45%) had good outcomes (independent
      walking or walking with 1 aid). CONCLUSION: Most SCI patients had acute,
      monophasic symptoms, reaching nadir in <24 h. The subjects frequently had acute
      pain near their lesions before SCI signs/symptoms (16/22 = 72.7%). Initial severe
      weakness (Medical Research Council score < or =2) and a young age at onset (55
      years old) are correlated with poor recovery of motor functions.

PMID- 18810238
TI  - Trends in risk factors, stroke subtypes and outcome. Nineteen-year data from the
      Sagrat Cor Hospital of Barcelona stroke registry.
AB  - BACKGROUND: Prospective stroke registries allow analyzing important aspects of
      the natural history of acute cerebrovascular events. Using the Sagrat Cor
      Hospital of Barcelona Stroke Registry, we aimed to determine trends in risk
      factors, stroke subtypes, prognosis and in-hospital mortality over 19 years in
      hospitalized stroke patients. METHODS: The study population consisted of 2,416
      first-ever stroke patients (ischemic stroke, n = 2,028; intracerebral hemorrhage,
      n = 334) included in the stroke registry up to December 31, 2004. Temporal trends
      in stroke patient characteristics for the periods 1986-1992, 1993-1998 and 1999
      2004 were assessed. RESULTS: Age was significantly different among the analyzed
      periods (p < 0.001), showing an increment in older patients throughout time.
      Hypertension (p = 0.001), diabetes (p = 0.004), ischemic heart disease (p =
      0.002) and atrial fibrillation increased (p = 0.000) as opposed to heavy smoking
      (p = 0.000) and history of TIA (p = 0.025). The mortality rate and the length of
      hospital stay decreased (p = 0.001), whereas transfer to
      convalescent/rehabilitation units increased (p = 0.001). CONCLUSIONS: An
      improvement in acute-stroke management and possibly evolution of cerebrovascular
      risk factors is reflected by changes in the risk factors and outcome of first
      ever stroke patients admitted to a stroke unit over a 19-year time span.

PMID- 18810239
TI  - Serum urate predicts long-term risk of acute coronary events in women after a
      transient ischaemic attack and stroke.
AB  - BACKGROUND: Several studies have shown serum urate to be an independent risk
      factor for vascular disease, but others have not, although a stronger association
      in women than in men has been a consistent finding. Studies of stroke patients
      have shown possible associations between urate level and stroke severity, but
      there have been no large cohort studies of the effect of urate on the long-term
      risk of future vascular events in patients with a transient ischaemic attack
      (TIA) or stroke. We studied this relationship in 2 independent cohorts. METHODS:
      Individual data on 15,483 patient-years of follow-up from the UK-TIA trial
      (13,182 patient-years) and the Oxford TIA study (2,301 patient-years) were
      analyzed. Hazard ratios (per unit increase of baseline urate in mg/dl) for the
      risks of stroke and acute coronary events (ACE) were obtained from Cox models
      stratified by study, with and without adjustment for potential confounders.
      Potential interactions between urate and baseline characteristics were also
      assessed. RESULTS: Linear associations between urate and risk of ACE were found
      in both studies: pooled age- and sex-adjusted hazard ratio = 1.17, 95% CI 1.06
      1.30, per unit increase of urate (p = 0.003). Sex, body mass index and previous
      myocardial infarction or angina were effect modifiers, but only the effect of sex
      remained after adjustment for other risk factors (p = 0.002), with a 5th:1st
      quintile hazard ratio of 4.23 (1.97-9.07, p < 0.0001) in women and 1.09 (0.70
      1.71, p = 0.69) in men. These findings were consistent across the 2 studies. No
      associations were found between urate level and either risk or severity of
      stroke. CONCLUSIONS: High urate levels were independent predictors of long-term
      risk of ACE in women who had a TIA or stroke, but not in men, in 2 independent
      studies. Urate levels could be useful in identifying women at high risk of
      coronary events in routine practice.

PMID- 18810240
TI  - Psocare: Italy shows the way in postmarketing studies.

PMID- 18810241
TI  - Impact of body mass index and obesity on clinical response to systemic treatment
      for psoriasis. Evidence from the Psocare project.
AB  - OBJECTIVE: Our aim was to assess the role of the body mass index (BMI) in the
      clinical response to systemic treatment for psoriasis. METHODS: A nationwide
      cohort study of patients receiving a new systemic treatment for plaque psoriasis
      at reference centres in Italy was conducted. Information was gathered through a
      web-based electronic form. Patients being maintained on the same medication and
      with data available at 8 and 16 weeks by March 31, 2007, were eligible. The
      outcome was a reduction in the Psoriasis Area Severity Index (PASI) of at least
      75% at follow-up compared to baseline (PASI-75). RESULTS: Out of 8,072 patients
      enrolled, 2,368 were eligible and analysable at 8 weeks and 2,042 at 16 weeks.
      PASI-75 was achieved by 819 patients (34.5%) at 8 weeks and 1,034 (50.6%) at 16
      weeks. The proportion steadily decreased with increased values of BMI. Compared
      to normal weight (BMI = 20-24) the adjusted odds ratio for achieving PASI-75 in
      obese patients was 0.73 (95% CI = 0.58-0.93) at 8 weeks and 0.62 (95% CI = 0.49
      0.79) at 16 weeks. The impact of the BMI did not show remarkable variations
      according to the drug prescribed at entry. CONCLUSION: The BMI affects the early
      clinical response to systemic treatment for psoriasis.

PMID- 18810242
TI  - Changes in neuropsychological functioning during alcohol detoxification.
AB  - This study investigates changes in neuropsychological functioning during early
      abstinence from alcohol. 30 alcohol-dependent inpatients were tested at intake
      (day 4 of admission) and post detoxification (day 26), using a test-retest
      design. The neuropsychological battery included measures of pre-morbid IQ, full
      scale IQ, verbal and non-verbal measures of memory and executive function. IQ was
      within the normal range at intake and comparable with age-adjusted normative
      values and there were some impairments in memory and executive function. There
      were significant increases in performance scores post detoxification in working
      memory, verbal fluency and verbal inhibition but not in non-verbal executive
      function tasks (mental flexibility and planning ability). Despite increased
      scores on tests of verbal and memory skills after 3 weeks of abstinence, complex
      executive abilities showed little change. These may have a negative impact on
      engagement and response to treatment and compromise clinical outcomes,
      heightening the risk of relapse.

PMID- 18810243
TI  - Effect of cannabinoid receptor agonists on streptozotocin-induced hyperalgesia in
      diabetic neuropathy.
AB  - The effect of CB-1 and CB-2 receptor agonists, as well as an influence of a non
      selective inhibitor of nitric oxide synthase (NOS), L-NOArg, and an inhibitor
      acting preferentially on cyclooxygenase-1 (COX-1), indomethacin, on the action of
      cannabinoid receptor agonists in a streptozotocin (STZ)-induced neuropathic model
      was investigated. When administered alone, a non-selective cannabinoid receptor
      agonist, WIN 55,212-2, a potentially selective CB-1 cannabinoid receptor agonist,
      Met-F-AEA, and a selective CB-2 cannabinoid receptor agonist, AM1241, dose
      dependently reduced STZ-induced hyperalgesia. The results of the present study
      also demonstrated that inhibitors of COX and NOS increase antihyperalgesic
      activity of low doses of CB-1 and CB-2 receptor agonists. Hypothetical
      consequences of this phenomenon are discussed.

PMID- 18810244
TI  - Cardioprotective role of sodium thiosulfate on chronic heart failure by
      modulating endogenous H2S generation.
AB  - BACKGROUND/AIMS: Sodium thiosulfate (STS) has been shown to be an antioxidant and
      calcium solubilizer, but the possible role of STS in dysfunctional ventricles
      remains unknown. Here, we assessed the effects of STS in the failing heart.
      METHODS: Heart failure was created by an arteriovenous fistula (AVF). Mice were
      divided into 4 groups: sham, AVF, sham + STS, and AVF + STS. STS (3 mg/ml) was
      supplemented with drinking water for 6 weeks in the appropriate surgery groups
      after surgery. RESULTS: M-mode echocardiograms showed ventricular contractile
      dysfunction with reduced aortic blood flow in AVF mice, whereas STS treatment
      prevented the decline in cardiac function. Ventricular collagen, MMP-2 and -9,
      and TIMP-1 were robustly increased with a decreasing trend in adenylate cyclase
      VI expression; however, STS supplementation reversed these effects in AVF mice.
      Among 2 enzymes that produce endogenous hydrogen sulfide (H(2)S), cystathionine
      gamma-lyase (CSE) expression was attenuated in AVF mice with no changes in
      cystathionine-beta-synthase (CBS) expression. In addition, reduced production of
      H(2)S in AVF ventricular tissue was normalized with STS supplementation.
      Moreover, cardiac tissues were more responsive to H(2)S when AVF mice were
      supplemented with STS compared to AVF alone. CONCLUSIONS: These results suggested
      that STS modulated cardiac dysfunction and the extracellular matrix, in part, by
      increasing ventricular H(2)S generation.

PMID- 18810245
TI  - Analysis of cerebrospinal fluid of Alzheimer patients. Biomarkers and toxic
      properties.
AB  - Alzheimer's disease (AD) is a severe, progressive and chronic disorder with
      strong cognitive deficits. Diagnosis of probable AD can be performed by measuring
      biomarkers in cerebrospinal fluid (CSF). The aim of the present study was to
      measure CSF levels of nerve growth factor (NGF), the anti-NGF auto-antibody, and
      the cholinesterases AChE and BChE, and to correlate them with beta-amyloid, tau
      and phospho-tau-181. We could show that NGF-like immunoreactivity, but not anti
      NGF auto-antibody, was significantly enhanced in AD patients compared to healthy
      subjects, while both cholinesterases were not changed. beta-Amyloid(1-42) was
      decreased, while tau and phospho-tau-181 were increased. The commercial Promega
      NGF ELISA detected mature NGF but not wild-type-human-pro-NGF. Using a bioassay
      of brain slices, we showed that recombinant mature NGF enhanced survival of
      cholinergic neurons, while wild-type human pro-NGF displayed a less pronounced
      effect. The addition of CSF to brain slices exhibited strong toxic effects on the
      survival of cholinergic neurons. We conclude that in CSF of AD patients (at least
      partly) mature NGF-like immunoreactivity is enhanced, and is masked in a bioassay
      by the toxic properties of CSF.

PMID- 18810246
TI  - Impact of MDR1 haplotypes derived from C1236T, G2677T/A and C3435T on the
      pharmacokinetics of single-dose oral digoxin in healthy Chinese volunteers.
AB  - OBJECTIVE: To investigate the effect of single-nucleotide polymorphisms (SNPs)
      and the haplotypes of MDR1 on the pharmacokinetics of single-dose digoxin in
      healthy Chinese volunteers. METHODS: After the genotypes of the MDR1 alleles of
      interest (G1199A, C1236T, G2677T/A and C3435T) had been determined, 20 subjects
      with the predominant haplotypes (TTT, CGC, TGC and CAC, in the order of position
      1236-2677-3435) were selected and administered with 0.25 mg of digoxin. Venous
      blood samples were taken from 0 to 4 h after dosing, and the pharmacokinetic
      parameters were calculated using the Drug and Statistics software. RESULTS: No
      mutation allele of G1199A was found in this study, the frequencies of the C1236T,
      G2677T/A and C3435T genetic variants were 65.2, 41.2, 17.3 and 39.7%,
      respectively. The 4 haplotypes TTT, TGC, CGC and CAC were present in more than
      90% of Chinese Han subjects, and an incomplete linkage between C3435T in exon 26,
      G2677T in exon 21 and C1236T in exon 12 was found. The peak concentration in
      plasma, the time to reach the peak concentration and the area under the plasma
      concentration/time curve between 0 and 4 h were used as indices of digoxin
      absorption. They were significantly different between subjects with the
      haplotypes TGC-CGC and those with TTT-TTT (p < 0.05). No significant difference
      was found when volunteers were grouped according to the haplotypes derived from
      G2677T and C3435T or disparate SNPs. CONCLUSION: Our findings indicated that the
      MDR1 haplotype derived from C1236T, G2677T/A and C3435T is superior to predict
      the pharmacokinetics of digoxin. Digoxin pharmacokinetics are significantly
      different between individuals with the TTT-TTT haplotype and those with TGC-CGC.

PMID- 18810247
TI  - The anaesthetic steroid alphaxalone positively modulates alpha1-glycine receptor
      function.
AB  - Inhibitory synaptic transmission within the dorsal horn of the spinal cord plays
      a key role in the processing of nociceptive signals, and mainly involves glycine.
      We have studied the effects of alphaxalone on alpha(1) homomeric glycine
      receptors expressed in a mammalian expression system (HEK 293 cells) using the
      whole-cell patch-clamp technique. Our experiments showed a coactivating effect of
      alphaxalone with a concentration for half-maximum activation (EC(50)) of the
      effect of a low glycine concentration (EC(20)) of 70.9 +/- 21.5 micromol/l.
      Taking into account the results of other groups, our study suggests that
      neuroactive steroids might be an interesting class of compounds to probe subunit
      specific effects of glycine receptors.

PMID- 18810248
TI  - Orally administered rapamycin, dacarbazine or both for treatment of human
      melanoma evaluated in severe combined immunodeficiency mice.
AB  - OBJECTIVE: In this experimental study, the antineoplastic potential of orally
      administered rapamycin in human melanoma was evaluated and compared with
      dacarbazine (DTIC) as well as with the antineoplastic effect of the combination
      of both drugs. METHODS: The substances were tested using 2 human melanoma cell
      lines, 518A2, which is highly susceptible to DTIC, and 607B, which is moderately
      susceptible. A human melanoma severe combined immunodeficiency mouse
      xenotransplantation model was used. After development of palpable tumors, mice
      received oral rapamycin or saline over 18 days. Additionally, from treatment day
      4 to 8, mice were randomly chosen to receive either DTIC or saline treatment.
      RESULTS: The oral rapamycin treatment (1.5, 7.5, 15 and 30 mg/kg body weight) had
      an antineoplastic effect, ranging from 35 to 78% tumor weight reduction compared
      with the saline group. In DTIC less sensitive 607B tumors, rapamycin treatment
      (15 and 30 mg/kg body weight) was superior to DTIC treatment (p < 0.05). DTIC
      monotreatment reduced tumor weight in 518A2 tumors by 85% on average, whereas in
      607B xenografts, no significant tumor weight reduction was observed compared with
      the saline group (p > 0.05). The combination of rapamycin and DTIC was not
      superior to rapamycin monotreatment in any cell line. CONCLUSION: These data
      indicate that oral rapamycin exerts a relevant antineoplastic effect on human
      melanoma cells. This effect appeared to be more pronounced in DTIC less sensitive
      melanoma xenografts.

PMID- 18810249
TI  - A rapid and sensitive screening system for human type I collagen with the aim of
      discovering potent anti-aging or anti-fibrotic compounds.
AB  - This study was undertaken with the aim of developing an easy and quick means of
      analyzing the effect of various compounds on the synthesis and secretion of human
      type I collagen at the protein level. A modification of the ELISA method was used
      on HFF-1 cells. For the proof of concept, we used thirteen compounds most of
      which are known to be antioxidants. Each compound was tested at concentrations of
      0, 10 and 100 microM on HFF-1 cells for 24 h. Thirteen sets of experiments for
      each compound were performed in ANOVA with three replicates. Duncan multiple
      range test (DMRT) was used to compare the mean values obtained from the treatment
      groups. From the results it was concluded that Vitamin C, undecylenic acid,
      conjugated linoleic acid, glycolic acid, and citric acid at 100 microM
      concentration could be used for anti-wrinkling or protection from premature
      aging, which requires enhancement of collagen synthesis. Lactic acid, EGCG,
      resveratrol, and retinol that can inhibit collagen synthesis effectively in a
      dose-dependent manner may be used for anti-fibrosis treatment purposes.

PMID- 18810254
TI  - Mice, mitochondria and myopathy.

PMID- 18810251
TI  - Yersinia pseudotuberculosis induces transcytosis  of nanoparticles across human
      intestinal villus  epithelium via invasin-dependent macropinocytosis.
AB  - Crohn's disease is characterized by a defect in intestinal barrier function,
      where bacteria are considered the most important inflammation-driving factor.
      Enteric bacteria, including E. coli and Yersinia spp, affect tight junctions in
      enterocytes, but little is known about bacterial effects on the transcellular
      pathway. Our objective was to study the short-term effects of Y.
      pseudotuberculosis on uptake of nanoparticles across human villus epithelium.
      Monolayers of human colon epithelium-derived Caco-2 cells and biopsies of normal
      human ileum were studied after 2 h exposure to Y. pseudotuberculosis expressing
      (inv+) or lacking (inv-) the bacterial adhesion molecule, invasin.
      Transepithelial transport of fluorescent nanoparticles (markers of transcytosis)
      was quantified by flow cytometry, and mechanisms explored by using inhibitors of
      endocytosis. Epithelial expressions of beta1-integrin and particle uptake
      pathways were studied by confocal microscopy. The paracellular pathway was
      assessed by electrical resistance (TER), mannitol flux, and expression of tight
      junction proteins occludin and caludin-4 by confocal microscopy. Inv+ Y.
      pseudotuberculosis adhered to the apical surface of epithelial cells and induced
      transcytosis of exogenous nanoparticles across Caco-2 monolayers (30-fold
      increase, P<0.01) and ileal mucosa (268+/-47% of control; P<0.01), whereas inv
      bacteria had no effect on transcytosis. The transcytosis was concentration-,
      particle size- and temperature-dependent, and possibly mediated via
      macropinocytosis. Y. pseudotuberculosis also induced apical expression of beta1
      integrin on epithelial cells. A slight drop in TER was seen after exposure to
      inv+ Y. pseudotuberculosis, whereas mannitol flux and tight junction protein
      expression was unchanged. In summary, Y. pseudotuberculosis induced apical
      expression of beta1-integrin and stimulated uptake of nanoparticles via invasin
      dependent transcytosis in human intestinal epithelium. Our findings suggest that
      bacterial factors may initiate transcytosis of luminal exogenous particles across
      human ileal mucosa, thus presenting a novel mechanism of intestinal barrier
      dysfunction.

PMID- 18810255
TI  - How HIV sneaks past the blood-brain barrier.

PMID- 18810257
TI  - Animals on 'hold'. Experimental protocols are essential.

PMID- 18810258
TI  - Animals on 'hold'.

PMID- 18810259
TI  - Animals on 'hold'. Risky assumptions.

PMID- 18810260
TI  - Animals on 'hold'. Approval spot-check.

PMID- 18810261
TI  - Snout deviation and eye protrusion in a male rat.

PMID- 18810263
TI  - Cerebellomedullary cerebrospinal fluid collection in the dog.
AB  - Analysis of cerebrospinal fluid (CSF) can be a valuable diagnostic tool. This
      column describes cerebellomedullary CSF collection in the dog.

PMID- 18810264
TI  - The 'Triad of Noncompliance' as a tool for understanding, preventing and
      correcting protocol and procedural noncompliance.
AB  - Noncompliance at research institutions can take many forms, including off
      protocol use of animals and failure to follow institutional requirements such as
      wearing personal protective equipment. Working with investigators to achieve full
      compliance after protocol approval is a key responsibility of laboratory
      veterinary staff, compliance personnel and the ACUC. The author discusses three
      main factors that lead to most noncompliance incidents: (i) Lack of Information,
      (ii) Desperation and (iii) Disregard. Understanding these three concepts,
      collectively termed 'The Triad of Noncompliance', can provide insight into the
      source of protocol or procedural noncompliance and can assist ACUC members and
      veterinary staff in formulating specific strategies to prevent and correct such
      problems.

PMID- 18810265
TI  - Sentience and sensation.
AB  - When animals are used in a biomedical research activity that may result in more
      than mild or momentary pain or distress, humanity, federal regulations and common
      sense direct us to use the least sentient species that can fulfill the aims of
      the research. The use of a less-sentient species is in line with the concept of
      Replacement, one of the well-known 3Rs of laboratory animal use. But what is a
      less-sentient species? Is a chimpanzee less sentient than a human; is a dog less
      sentient than a chimpanzee; and is a mouse less sentient than a dog? Does 'less
      sentient' imply that a species is less able to experience pain, is less
      intelligent or has less self-awareness? This essay will explore some of the
      relationships between sentience, pain and vertebrate phylogeny.

PMID- 18810266
TI  - Electrocardiographic changes in rats undergoing thoracic surgery under combined
      parenteral anesthesia.
AB  - To compare two protocols of combined parenteral general anesthesia, the authors
      analyzed electrocardiographic changes in anesthetized rats undergoing left
      pneumonectomy. One group of rats was anesthetized with a combination of
      medetomidine and ketamine (group 1, n = 10), and the other was injected with
      diazepam and ketamine (group 2, n = 10). Investigators obtained two
      electrocardiograms from each rat, one before surgery (5 min after anesthesia) and
      one after surgery (60 min after anesthesia). Anesthetic induction was quick for
      all rats, though four rats in group 2 died before surgery. Mean cardiac frequency
      and R-wave amplitude were significantly lower in rats in group 1 than in rats in
      group 2. Rats in group 1 received injections of atipamezole about 60 min after
      surgery, which reversed the effects of medetomidine; these rats regained
      voluntary respiratory movement more quickly than did rats in group 2. Two
      additional rats in group 2 died during postsurgical recovery. These results
      suggest that for thoracic surgery in rats, medetomidine-ketamine is an
      appropriate anesthetic combination, may be safer than diazepam-ketamine and
      yields a shorter recovery time.

PMID- 18810267
TI  - Environment, migratory tendency, phylogeny and basal metabolic rate in birds.
AB  - Basal metabolic rate (BMR) represents the minimum maintenance energy requirement
      of an endotherm and has far-reaching consequences for interactions between
      animals and their environments. Avian BMR exhibits considerable variation that is
      independent of body mass. Some long-distance migrants have been found to exhibit
      particularly high BMR, traditionally interpreted as being related to the
      energetic demands of long-distance migration. Here we use a global dataset to
      evaluate differences in BMR between migrants and non-migrants, and to examine the
      effects of environmental variables. The BMR of migrant species is significantly
      higher than that of non-migrants. Intriguingly, while the elevated BMR of
      migrants on their breeding grounds may reflect the metabolic machinery required
      for long-distance movements, an alternative (and statistically stronger)
      explanation is their occupation of predominantly cold high-latitude breeding
      areas. Among several environmental predictors, average annual temperature has the
      strongest effect on BMR, with a 50% reduction associated with a 20 degrees C
      gradient. The negative effects of temperature variables on BMR hold separately
      for migrants and non-migrants and are not due their different climatic
      associations. BMR in migrants shows a much lower degree of phylogenetic inertia.
      Our findings indicate that migratory tendency need not necessarily be invoked to
      explain the higher BMR of migrants. A weaker phylogenetic signal observed in
      migrants supports the notion of strong phenotypic flexibility in this group which
      facilitates migration-related BMR adjustments that occur above and beyond
      environmental conditions. In contrast to the findings of previous analyses of
      mammalian BMR, primary productivity, aridity or precipitation variability do not
      appear to be important environmental correlates of avian BMR. The strong effects
      of temperature-related variables and varying phylogenetic effects reiterate the
      importance of addressing both broad-scale and individual-scale variation for
      understanding the determinants of BMR.

PMID- 18810268
TI  - Characterization of parameters required for effective use of tamoxifen-regulated
      recombination.
AB  - Conditional gene targeting using the Cre-loxp system is a well established
      technique in numerous in vitro and in vivo systems. Ligand regulated forms of Cre
      have been increasingly used in these applications in order to gain temporal and
      spatial control over conditional targeting. The tamoxifen-regulated Cre variant
      mer-Cre-mer (mCrem) is widely utilized because of its reputation for tight
      regulation in the absence of its tamoxifen ligand. In the DT40 chicken B cell
      line, we generated an mCrem-based reversible switch for conditional regulation of
      a transgene, and in contrast with previous work, observed significant
      constitutive activity of mCrem. This prompted us to use our system for analysis
      of the parameters governing tamoxifen-regulated mCrem recombination of a genomic
      target. We find that robust mCrem expression correlates with a high level of
      tamoxifen-independent Cre activity, while clones expressing mCrem at the limit of
      western blot detection exhibit extremely tight regulation. We also observe time
      and dose-dependent effects on mCrem activity which suggest limitations on the use
      of conditional targeting approaches for applications which require tight temporal
      coordination of Cre action within a cell population.

PMID- 18810269
TI  - Rapid nanoparticle-mediated monitoring of bacterial metabolic activity and
      assessment of antimicrobial susceptibility in blood with magnetic relaxation.
AB  - Considering the increased incidence of bacterial infections and the emergence of
      multidrug resistant bacteria at the global level, we designed superparamagnetic
      iron oxide nanoparticles as nanosensors for the assessment of antimicrobial
      susceptibility through magnetic relaxation. In this report, we demonstrate that
      iron oxide nanosensors, either dextran-coated supplemented with Con A or silica
      coated conjugated directly to Con A, can be used for the fast (1) quantification
      of polysaccharides, (2) assessment of metabolic activity and (3) determination of
      antimicrobial susceptibility in blood. The use of these polysaccharide
      nanosensors in the determination of antimicrobial susceptibility in the clinic or
      the field, and the utilization of these nanoprobes in pharmaceutical R&D are
      anticipated.

PMID- 18810270
TI  - Metagenomic analysis of lysogeny in Tampa Bay: implications for prophage gene
      expression.
AB  - Phage integrase genes often play a role in the establishment of lysogeny in
      temperate phage by catalyzing the integration of the phage into one of the host's
      replicons. To investigate temperate phage gene expression, an induced viral
      metagenome from Tampa Bay was sequenced by 454/Pyrosequencing. The sequencing
      yielded 294,068 reads with 6.6% identifiable. One hundred-three sequences had
      significant similarity to integrases by BLASTX analysis (e < or =0.001). Four
      sequences with strongest amino-acid level similarity to integrases were selected
      and real-time PCR primers and probes were designed. Initial testing with
      microbial fraction DNA from Tampa Bay revealed 1.9 x 10(7), and 1300 gene copies
      of Vibrio-like integrase and Oceanicola-like integrase L(-1) respectively. The
      other two integrases were not detected. The integrase assay was then tested on
      microbial fraction RNA extracted from 200 ml of Tampa Bay water sampled biweekly
      over a 12 month time series. Vibrio-like integrase gene expression was detected
      in three samples, with estimated copy numbers of 2.4-1280 L(-1). Clostridium-like
      integrase gene expression was detected in 6 samples, with estimated copy numbers
      of 37 to 265 L(-1). In all cases, detection of integrase gene expression
      corresponded to the occurrence of lysogeny as detected by prophage induction.
      Investigation of the environmental distribution of the two expressed integrases
      in the Global Ocean Survey Database found the Vibrio-like integrase was present
      in genome equivalents of 3.14% of microbial libraries and all four viral
      metagenomes. There were two similar genes in the library from British Columbia
      and one similar gene was detected in both the Gulf of Mexico and Sargasso Sea
      libraries. In contrast, in the Arctic library eleven similar genes were observed.
      The Clostridium-like integrase was less prevalent, being found in 0.58% of the
      microbial and none of the viral libraries. These results underscore the value of
      metagenomic data in discovering signature genes that play important roles in the
      environment through their expression, as demonstrated by integrases in lysogeny.

PMID- 18810272
TI  - Simplivariate models: ideas and first examples.
AB  - One of the new expanding areas in functional genomics is metabolomics: measuring
      the metabolome of an organism. Data being generated in metabolomics studies are
      very diverse in nature depending on the design underlying the experiment.
      Traditionally, variation in measurements is conceptually broken down in
      systematic variation and noise where the latter contains, e.g. technical
      variation. There is increasing evidence that this distinction does not hold (or
      is too simple) for metabolomics data. A more useful distinction is in terms of
      informative and non-informative variation where informative relates to the
      problem being studied. In most common methods for analyzing metabolomics (or any
      other high-dimensional x-omics) data this distinction is ignored thereby severely
      hampering the results of the analysis. This leads to poorly interpretable models
      and may even obscure the relevant biological information. We developed a
      framework from first data analysis principles by explicitly formulating the
      problem of analyzing metabolomics data in terms of informative and non
      informative parts. This framework allows for flexible interactions with the
      biologists involved in formulating prior knowledge of underlying structures. The
      basic idea is that the informative parts of the complex metabolomics data are
      approximated by simple components with a biological meaning, e.g. in terms of
      metabolic pathways or their regulation. Hence, we termed the framework
      'simplivariate models' which constitutes a new way of looking at metabolomics
      data. The framework is given in its full generality and exemplified with two
      methods, IDR analysis and plaid modeling, that fit into the framework. Using this
      strategy of 'divide and conquer', we show that meaningful simplivariate models
      can be obtained using a real-life microbial metabolomics data set. For instance,
      one of the simple components contained all the measured intermediates of the
      Krebs cycle of E. coli. Moreover, these simplivariate models were able to uncover
      regulatory mechanisms present in the phenylalanine biosynthesis route of E. coli.

PMID- 18810273
TI  - Metal-containing proteins, macrocycles, and coordination complexes in therapeutic
      applications and disease.

PMID- 18810271
TI  - Herpes-virus infection in patients with Langerhans cell histiocytosis: a case
      controlled sero-epidemiological study, and in situ analysis.
AB  - BACKGROUND: Langerhans cell histiocytosis (LCH) is a rare disease that affects
      mainly young children, and which features granulomas containing Langerhans-type
      dendritic cells. The role of several human herpesviruses (HHV) in the
      pathogenesis of LCH was suggested by numerous reports but remains debated.
      Epstein-barr virus (EBV, HHV-4), & Cytomegalovirus (CMV, HHV-5) can infect
      Langerhans cells, and EBV, CMV and HHV-6 have been proposed to be associated with
      LCH based on the detection of these viruses in clinical samples. METHODOLOGY: We
      have investigated the prevalence of EBV, CMV and HHV-6 infection, the characters
      of antibody response and the plasma viral load in a cohort of 83 patients and 236
      age-matched controls, and the presence and cellular localization of the viruses
      in LCH tissue samples from 19 patients. PRINCIPAL FINDINGS: The results show that
      prevalence, serological titers, and viral load for EBV, CMV and HHV-6 did not
      differ between patients and controls. EBV was found by PCR in tumoral sample from
      3/19 patients, however, EBV small RNAs EBERs -when positive-, were detected by in
      situ double staining in bystander B CD20+ CD79a+ lymphocytes and not in CD1a+ LC.
      HHV-6 genome was detected in the biopsies of 5/19 patients with low copy number
      and viral Ag could not be detected in biopsies. CMV was not detected by PCR in
      this series. CONCLUSIONS/SIGNIFICANCE: Therefore, our findings do not support the
      hypothesis of a role of EBV, CMV, or HHV-6 in the pathogenesis of LCH, and
      indicate that the frequent detection of Epstein-barr virus (EBV) in Langerhans
      cell histiocytosis is accounted for by the infection of bystander B lymphocytes
      in LCH granuloma. The latter observation can be attributed to the
      immunosuppressive micro environment found in LCH granuloma.

PMID- 18810274
TI  - New tricks by an old dog.

PMID- 18810275
TI  - Rosiglitazone Suppresses the Growth and Invasiveness of SGC-7901 Gastric Cancer
      Cells and Angiogenesis In Vitro via PPARgamma Dependent and Independent
      Mechanisms.
AB  - Although thiazolidinediones (TZDs) were found to be ligands for peroxisome
      proliferators-activated receptorgamma (PPARgamma), the mechanism by which TZDs
      exert their anticancer effect remains unclear. Furthermore, the effect of TZDs on
      metastatic and angiogenesis potential of cancer cells is unknown. Our results in
      this paper show that rosiglitazone inhibited SGC-7901 gastric cancer cells
      growth, caused G1 cell cycle arrest and induced apoptosis in a dose-dependent
      manner. The effects of rosiglitazone on SGC-7901 cancer cells were completely
      reversed by treatment with PPARgamma antagonist GW9662. Rosiglitazone inhibited
      SGC-7901 cell migration, invasiveness, and the expression of MMP-2 in dose
      dependent manner via PPARgamma-independent manner. Rosiglitazone reduced the VEGF
      induced angiogenesis of HUVEC in dose-dependent manner through PPARgamma
      dependent pathway. Moreover, rosiglitazone did not affect the expression of VEGF
      by SGC-7901 cells. Our results demonstrated that by PPARgamma ligand,
      rosiglitazone inhibited growth and invasiveness of SGC-7901 gastric cancer cells
      and angiogenesis in vitro via PPARgamma-dependent or -independent pathway.

PMID- 18810276
TI  - The north and south of candidemia: Issues for Latin America.
AB  - Candidemia is a growing problem in tertiary care hospitals all over the world. It
      is generally difficult to diagnose, leads to prolonged hospitalization, has a
      mortality rate of around 50% and is a financial burden to healthcare systems. The
      different distribution profiles of Candida species underlying candidemia seen in
      Latin America, North America, Canada and Europe, along with the emergence of
      antifungal drug resistance, make it essential to optimize regional guidelines for
      treating hematogenous candidiasis. This article reviews the importance of
      candidemia epidemiology and diagnosis from region to region and highlights the
      antifungal agents currently available to clinicians, comparing antifungal
      susceptibility profiles that dominate therapeutic strategies for candidemia in
      specific high-risk populations.

PMID- 18810277
TI  - Recent developments in ambient ionization techniques for analytical mass
      spectrometry.
AB  - Ambient ionization techniques enable the interrogation of a variety of samples in
      their native state by mass spectrometry, and are rapidly advancing all fields
      where screening for the presence of various analytes in a broadband and/or high
      throughput fashion is desirable. This Highlight article provides an introduction
      to the field, and showcases the different ionization approaches reported since
      2004, with an emphasis on the most recent developments.

PMID- 18810278
TI  - Optical nanosensors--smart tools in bioanalytics.
AB  - Optical nanosensors are advanced analytical tools that combine advantages of
      conventional sensor technology with flexibility in use of dissolved indicators.
      Introduced a decade ago, optical nanosensors attract increasingly more attention
      each year. In fact, the number of reports on the topic has doubled in the last 2
      3 years. In this contribution, we aim to highlight recent developments of optical
      nanosensors and give an overview on strategies to design these nanosensors with
      different levels of complexity. Applications of this smart technology,
      advantages, challenges, and risks will be discussed.

PMID- 18810280
TI  - Genetic, genomic and physiological state studies on single-needle bio
      electrosprayed human cells.
AB  - Bio-electrospraying, a non-contact jet-based direct cell engineering approach,
      was recently pioneered and demonstrated for handling a wide range of primary
      living cells. In those studies, post-treated cells were biologically assessed in
      comparison to several controls by way of flow cytometry. Although flow cytometry
      accurately assesses those viable populations of cells, subtle effects at a sub
      cellular level could have been missed. Therefore, in the present study we
      demonstrate metaphase chromosome breakage studies carried out on single-needle
      bio-electrosprayed human T-lymphocytes, which are compared with several controls.
      The results indicate that post-treated T-lymphocytes do not demonstrate any
      increase in chromosome damage in comparison to control cells. These studies
      further validate bio-electrospraying as a technique with potential for clinical
      utility.

PMID- 18810279
TI  - Plasmon-controlled fluorescence: a new paradigm in fluorescence spectroscopy.
AB  - Fluorescence spectroscopy is widely used in biological research. Until recently,
      essentially all fluorescence experiments were performed using optical energy
      which has radiated to the far-field. By far-field we mean at least several
      wavelengths from the fluorophore, but propagating far-field radiation is usually
      detected at larger macroscopic distances from the sample. In recent years there
      has been a growing interest in the interactions of fluorophores with metallic
      surfaces or particles. Near-field interactions are those occurring within a
      wavelength distance of an excited fluorophore. The spectral properties of
      fluorophores can be dramatically altered by near-field interactions with the
      electron clouds present in metals. These interactions modify the emission in ways
      not seen in classical fluorescence experiments. In this review we provide an
      intuitive description of the complex physics of plasmons and near-field
      interactions. Additionally, we summarize the recent work on metal-fluorophore
      interactions and suggest how these effects will result in new classes of
      experimental procedures, novel probes, bioassays and devices.

PMID- 18810281
TI  - On-chip Raman analysis of heterogeneous catalytic reaction in supercritical CO2:
      phase behaviour monitoring and activity profiling.
AB  - Raman spectroscopy on a chip based Si/glass microreactor allows fast and
      simultaneous analysis of concentration profiles and phase behaviour of a
      heterogeneously catalyzed reaction at high pressure.

PMID- 18810282
TI  - SERRS immunoassay for quantitative human CRP analysis.
AB  - SERRS has been used for the first time for the measurement of C-reactive protein
      (CRP) in an immunoassay. CRP, a biological marker for the diagnosis of infection
      and inflammation, is quantified in an ELISA using conventional reagents, but the
      usual colorimetric detection step is replaced by SERRS detection, offering
      improved sensitivity and potential for multiplexing analysis.

PMID- 18810283
TI  - Microchip-based integration of cell immobilization, electrophoresis, post-column
      derivatization, and fluorescence detection for monitoring the release of dopamine
      from PC 12 cells.
AB  - In this paper, we describe the fabrication and evaluation of a multilayer
      microchip device that can be used to quantitatively measure the amount of
      catecholamines released from PC 12 cells immobilized within the same device. This
      approach allows immobilized cells to be stimulated on-chip and, through rapid
      actuation of integrated microvalves, the products released from the cells are
      repeatedly injected into the electrophoresis portion of the microchip, where the
      analytes are separated based upon mass and charge and detected through post
      column derivatization and fluorescence detection. Following optimization of the
      post-column derivatization detection scheme (using naphthalene-2,3
      dicarboxaldehyde and 2-beta-mercaptoethanol), off-chip cell stimulation
      experiments were performed to demonstrate the ability of this device to detect
      dopamine from a population of PC 12 cells. The final 3-dimensional device that
      integrates an immobilized PC 12 cell reactor with the bilayer continuous flow
      sampling/electrophoresis microchip was used to continuously monitor the on-chip
      stimulated release of dopamine from PC 12 cells. Similar dopamine release was
      seen when stimulating on-chip versus off-chip yet the on-chip immobilization
      studies could be carried out with 500 times fewer cells in a much reduced volume.
      While this paper is focused on PC 12 cells and neurotransmitter analysis, the
      final device is a general analytical tool that is amenable to the immobilization
      of a variety of cell lines and analysis of various released analytes by
      electrophoretic means.

PMID- 18810284
TI  - Novel superparamagnetic core-shell molecular imprinting microspheres towards high
      selective sensing.
AB  - Novel superparamagnetic core-shell imprinting microspheres (MCSIMs) were
      synthesized using magnetite microspheres with 350 nm diameter and 70 nm thickness
      silica gel to form core-shell Fe(3)O(4)/SiO(2) composite for template
      phenylephrine (Phen) recognition and high efficiency separation. Compared to the
      previous imprinting recognition, the main advantage of this strategy lies in two
      aspects: one is the high stability and monodispersity of the MCSIMs structure,
      the other is the use of superparamagnetic Fe(3)O(4)/SiO(2) microspheres as an
      immobilization matrix and separation tool, thus greatly simplifying time
      consuming washing steps. The affinity and selectivity of the MCSIMs were
      monitored by QCM and electrochemistry measurements. Imprinting microspheres have
      a remarkable affinity to Phen over that of structurally related molecules,
      including DA, EP, Phe and Tyr. The relative binding selectivity for different
      analytes estimated from amperometric signals was Phen : DA : EP = 40 : 5 : 1. The
      MCSIMs sensor showed a high sensitivity (400 microA mM(-1)), short response time
      (reaching 98% within 10 s), and broad linear response range from 1 microM to 0.1
      mM and low detection limit (0.1 microM). Additionally, the results of control
      experiments showed that only negligible signal was obtained for non-imprinting
      microspheres. This could be reasonably attributed to the unique surface pores,
      charges and especially the nature of the functional groups inside MCSIMs
      cavities.

PMID- 18810285
TI  - Isolation and pre-concentration of basic proteins in aqueous mixture via solid
      phase extraction with multi-walled carbon nanotubes assembled on a silica
      surface.
AB  - Multi-walled carbon nanotubes (MWNTs) were assembled on a silica surface using a
      polyelectrolyte-assisted layer-by-layer (LBL) assembly technique. The surface
      assembled silica spheres with MWNTs (MWNTs/SiO(2)), which serve as a novel solid
      phase extraction sorbent for separation/pre-concentration of basic proteins, was
      investigated. The adsorption behavior of cytochrome c (cyto-c) by MWNTs/SiO(2)
      spheres agrees well with the Langmuir adsorption model. A thorough scrutiny of
      the experimental parameters affecting the adsorption of cyto-c from aqueous
      solution onto the MWNTs/SiO(2) spheres and its subsequent desorption was carried
      out. A maximum adsorption capacity of cyto-c was derived as 112 mg (cyto-c) g(-1)
      (MWNTs). A distinct feature of the MWNTs/SiO(2)-packed micro-column provides
      clear advantages of minimized flow impedance when operated in a flow system, in
      addition to better separation efficiency as well as the favorable enrichment
      capability of proteins, characterized by an enrichment factor of 30 by using 2.0
      mL of aqueous solution. The practical applicability of the MWNTs/SiO(2) spheres
      as a sorbent for the isolation of basic proteins from acidic protein species was
      demonstrated by effective separation of cyto-c from bovine serum albumin (BSA).

PMID- 18810286
TI  - Selective extraction and elution of weak bases by in-line solid-phase extraction
      capillary electrophoresis using a pH step gradient and a weak cation-exchange
      monolith.
AB  - A polymer monolith bearing weak cation-exchange functionality was prepared for
      the purpose of demonstrating pH-selective extraction and elution in in-line solid
      phase extraction-capillary electrophoresis (SPE-CE) utilising a model set of
      cationic analytes, namely imidazole, lutidine and 3-phenylpropanamine.
      Optimization of the electrolyte conditions for efficient elution of the adsorbed
      analytes using a moving pH boundary required that the capillary and monolith be
      filled with 44 mM sodium acetate at high pH (pH 6) and a low pH electrolyte of 3
      mM sodium acetate pH 3 was placed in the electrolyte vials. This combination
      allowed the adsorbed analytes to be simultaneously eluted and focused into narrow
      bands, with peak widths of the eluted analytes having a baseline width of 1.2 s
      immediately after the monolith. Using these optimum elution conditions, the
      versatility of the SPE-CE approach was demonstrated by removing unwanted adsorbed
      components after extraction with a wash at a different pH and also by selecting a
      pH at which only some of the model weak bases were ionised. The analytical
      performance of the approach was evaluated and the relative standard deviation for
      peak heights, peak area and migration times were in the ranges of 1.4-5.3, 1.2
      3.3 and 0.4-1.2% respectively. Analytes exhibited linear calibrations with r(2)
      values ranging from 0.996 to 0.999 over two orders of magnitude. Analyte pre
      concentration provided excellent sensitivity, and limits of detection for the
      analyte used in this study were in the range 8.0-30 ng ml(-1), which was an
      enhancement of 63 when compared to normal hydrodynamic injection occupying 1.3%
      of the capillary of these bases in water.

PMID- 18810287
TI  - Ultratrace analysis of Antarctic snow samples by reaction cell inductively
      coupled plasma mass spectrometry using a total-consumption micro-sample
      introduction system.
AB  - In this work, a new sensitive procedure for the determination of ultratrace
      elements in snow samples based on quadrupole ICP-MS has been developed. After
      filtration through a 0.5 microm PTFE membrane (for dissolved element
      determination) or acidification with 0.5% nitric acid (for acid dissolvable
      element determination), the analytes were preconcentrated by sample volume
      reduction and analysed by ICP-MS. Micro-samples were efficiently introduced into
      the plasma source at 20 microl min(-1) uptake rate by using a PFA micronebulizer
      coupled to an evaporation chamber of the torch integrated sample introduction
      system (TISIS). As a result, the amount of sample required was about one order of
      magnitude lower than that required with a conventional liquid sample introduction
      system. In order to improve the transport efficiency, the TISIS chamber was
      electrically-heated at 70 degrees C and a sheathing gas stream was used to
      protect the aerosol from the chamber walls. Under these conditions, negative
      solvent plasma effects were no more severe than for conventional systems, because
      the total solvent plasma load was 20 mg min(-1). The operating parameters were
      optimized to obtain maximum sensitivity, while limiting oxides and double charge
      ion formation. The polyatomic interferences were removed by applying the dynamic
      reaction cell (DRC) technique, using ammonia as the reaction gas. Under the
      optimized conditions, limits of detection ranged from 0.02 to 4.5 pg g(-1),
      allowing the determination of Cr, V, Fe, Mn, Pb, Zn, Cd, Co and Cu in Antarctic
      snow samples. Signal repeatability was lower than 10% which prevented the use of
      an internal standard. Precision of the procedure ranged from 2.0% to 5.6%. The
      accuracy of the method was verified by the analysis of both certified reference
      water and surface snow samples collected in coastal and inland areas of
      Antarctica. The DRC program used, the short wash out and signal stabilization
      times registered under these conditions led to a 10 h(-1) sample throughput.

PMID- 18810288
TI  - Utilization of spectral vector properties in multivariate chemometrics analysis
      of hyperspectral infrared imaging data for cellular studies.
AB  - A suite of numerical techniques was utilized in a concerted fashion for the
      efficacious multivariate chemometrics analysis of hyperspectral infrared imaging
      data of exfoliated oral mucosa cells. Based on the vector representation of
      infrared spectrum a1xnu), spectral vector properties (SVP) are demonstrated to
      possess underpinning spectral information that was exploited in crucial
      chemometrics analyses; which include outlier spectra identification, selection
      for a subset of imaged mid-infrared spectra that contain good oral mucosa cell
      signals, and, for the first time, obtain major biochemical constituent spectra
      via the band-target entropy minimization (BTEM) curve resolution algorithm. The
      relative concentration spatial distribution of the major biochemical constituents
      observed, namely membrane lipids and various cellular protein structures (alpha
      helix, beta-sheet, turns and bends), were subsequently acquired through multi
      linear regression and were displayed as chemical contour maps. Amongst the set of
      numerical algorithms employed, two novel unsupervised clustering algorithms were
      developed and tested. One is useful for outlier spectra detection, and the other
      aids the selection of pertinent spatially distributed spectra that possess oral
      mucosa cell mid-infrared spectra with good signal-to-noise ratio. It is
      anticipated that this developed numerical suite will serve as an effective
      multivariate chemometrics protocol for cellular studies and biomedical
      diagnostics via infrared imaging.

PMID- 18810289
TI  - A near-infrared fluorescent probe for lipid hydroperoxides in living cells.
AB  - An NIR (near-infrared) fluorescent probe TCP (tricarbocyanine diphenylphosphine)
      including a non-conjugated 'pre-tricarbocyanine' was designed and synthesized for
      visualizing lipid hydroperoxides (ROOH) in living cells. The excitation and
      emission spectra of tricarbocyanine in the NIR region can effectively avoid
      background fluorescence interference in biological systems. The probe exhibited a
      rapid fluorescence response to ROOH and high selectivity for ROOH over other ROS
      (reactive oxygen species) and some biological compounds, and the limit of
      detection was 38 pM. In addition, the probe was stable, and less cytotoxic, which
      indicated that it has potential application in detecting lipid hydroperoxides in
      living biological systems.

PMID- 18810290
TI  - Analysis of single blood cells for CSF diagnostics via a combination of
      fluorescence staining and micro-Raman spectroscopy.
AB  - This contribution provides a new approach for single blood cell analysis in
      cerebrospinal fluid (CSF) with the possibility of utilizing simultaneously on the
      same sample the unique capabilities of the two methods fluorescence staining and
      Raman spectroscopy. By doing so this technique enables the potential of accurate
      and rapid cell identification in order to determine cell parameters immediately
      (e.g. the study of the level of activation or phagocytosis activity of single
      blood cells). Fluorescence labeling of blood cells offers the great possibility
      of differentiating easily between the subtypes of white blood cells, while Raman
      spectroscopy reveals molecular fingerprint information with a spatial resolution
      down to the diffraction limit. Compared to an unstained cell, the presented
      results nicely demonstrate that the selected fluorescence dye does not influence
      the Raman spectrum of a labeled blood cell notably. By the combined application
      of Raman spectroscopy and statistical data analysis a distinction between white
      blood cell substructures could be performed. Since several blood cell types also
      differ in the amount of their cell components, differentiation between several
      blood cell types is also possible when one blood cell is described in the
      database by several Raman spectra according their presented sub-microscopic
      structures. This capability with the possibility of accurate and rapid blood cell
      identification in cerebrospinal fluid is extremely promising for implementation
      in clinical diagnostics.

PMID- 18810291
TI  - Rapid and quantitative detection of the microbial spoilage in milk using Fourier
      transform infrared spectroscopy and chemometrics.
AB  - Microbiological safety plays a very significant part in the quality control of
      milk and dairy products worldwide. Current methods used in the detection and
      enumeration of spoilage bacteria in pasteurized milk in the dairy industry,
      although accurate and sensitive, are time-consuming. FT-IR spectroscopy is a
      metabolic fingerprinting technique that can potentially be used to deliver
      results with the same accuracy and sensitivity, within minutes after minimal
      sample preparation. We tested this hypothesis using attenuated total reflectance
      (ATR), and high throughput (HT) FT-IR techniques. Three main types of pasteurized
      milk - whole, semi-skimmed and skimmed - were used and milk was allowed to spoil
      naturally by incubation at 15 degrees C. Samples for FT-IR were obtained at
      frequent, fixed time intervals and pH and total viable counts were also recorded.
      Multivariate statistical methods, including principal components-discriminant
      function analysis and partial least squares regression (PLSR), were then used to
      investigate the relationship between metabolic fingerprints and the total viable
      counts. FT-IR ATR data for all milks showed reasonable results for bacterial
      loads above 10(5) cfu ml(-1). By contrast, FT-IR HT provided more accurate
      results for lower viable bacterial counts down to 10(3) cfu ml(-1) for whole milk
      and, 4 x 10(2) cfu ml(-1) for semi-skimmed and skimmed milk. Using FT-IR with
      PLSR we were able to acquire a metabolic fingerprint rapidly and quantify the
      microbial load of milk samples accurately, with very little sample preparation.
      We believe that metabolic fingerprinting using FT-IR has very good potential for
      future use in the dairy industry as a rapid method of detection and enumeration.

PMID- 18810292
TI  - Biomechanical analysis of cancerous and normal cells based on bulge generation in
      a microfluidic device.
AB  - This paper presents a new biomechanical analysis method for discrimination
      between cancerous and normal cells through compression by poly(dimethylsiloxane)
      (PDMS) membrane deflection in a microfluidic device. When a cell is compressed,
      cellular membrane will expand and then small bulges will appear on the peripheral
      cell membrane beyond the allowable strain. It is well known that the amount of F
      actin in cancer cells is less than that of normal cells and bulges occur at the
      sites where cytoskeleton becomes detached from the membrane bilayer. Accordingly,
      we have demonstrated the difference of the bulge generation between breast cancer
      cells (MCF7) and normal cells (MCF10A). After excessive deformation, the bulges
      generated in MCF7 cells were not evenly distributed on the cell periphery.
      Contrary to this, the bulges of MCF10A cells showed an even distribution. In
      addition, the morphologies of bulges of MCF7 and MCF10A cells looked swollen
      protrusion and tubular protrusion, respectively. Peripheral strains at the moment
      of the bulge generation were also 72% in MCF7 and 46% in MCF10A. The results show
      that the bulge generation can be correlated with the cytoskeleton quantity inside
      the cell, providing the first step of a new biomechanical approach.

PMID- 18810293
TI  - Electronic integrated multisensor tongue applied to grape juice and wine
      analysis.
AB  - An integrated multisensor composed by six ISFET devices selective to common ions
      and heavy metals combined with a flow injection analysis (FIA) system has been
      applied as an electronic tongue to grape juice and wine sample analysis. The data
      obtained for several grape and wine variety samples analysis have been treated
      using multiparametric tools like principal component analysis (PCA) and soft
      independent modelling class analogy technique (SIMCA) for the patterning
      recognition and classification of samples and partial least squares (PLS)
      regression for quantification of several parameters of interest in wine
      production. The results obtained have demonstrated the potential of using those
      multisensors as electronic tongues not only for distinguishing the samples
      according to the grape variety and the vintage year but also for quantitative
      prediction of several sample parameters.

PMID- 18810294
TI  - Towards quantitatively reproducible substrates for SERS.
AB  - There is a need for a method to facilitate the development of novel, reproducible
      colloidal surface-enhanced Raman scattering (SERS) substrates to encourage the
      use of SERS in applied studies. In this study we show for the first time that by
      using suitably designed SERS experiments in conjunction with multivariate
      analysis of variance (MANOVA), an objective assessment of colloidal SERS
      reproducibility can be made. This is demonstrated with the analyte cresyl violet,
      but could be extended to any analyte of interest for which reproducible SERS data
      are needed.

PMID- 18810295
TI  - Bibliometrics, a new way to help a scientific board prepare a world scientific
      congress.

PMID- 18810296
TI  - Effects of dietary protein on the composition of weight loss in post-menopausal
      women.
AB  - OBJECTIVES: To determine whether a hypocaloric diet higher in protein can prevent
      the loss of lean mass that is commonly associated with weight loss. DESIGN: An
      intervention study comparing a hypocaloric diet moderately high in protein to one
      lower in protein. SETTING: Study measurements were taken at the Wake Forest
      University General Clinical Research Center (GCRC) and Geriatric Research Center
      (GRC). PARTICIPANTS: Twenty-four post-menopausal, obese women (mean age = 58 +/-
      6.6 yrs; mean BMI = 33.0 +/- 3.6 kg/m2). INTERVENTION: Two 20-week hypocaloric
      diets (both reduced by 2800 kcal/wk) were compared: one maintaining dietary
      protein intake at 30% of total energy intake (1.2-1.5 g/kg/d; HI PROT), and the
      other maintaining dietary protein intake at 15% of total energy (0.5-0.7 g/kg/d;
      LO PROT). The GCRC metabolic kitchen provided lunch and dinner meals which the
      women picked up 3 days per week and ate outside of the clinic. MEASUREMENTS: Body
      composition, including total body mass, total lean mass, total fat mass, and
      appendicular lean mass, assessed by dual energy x-ray absorptiometry, was
      measured before and after the diet interventions. RESULTS: The HI PROT group lost
      8.4 +/- 4.5 kg and the LO PROT group lost 11.4 +/- 3.8 kg of body weight (p =
      0.11). The mean percentage of total mass lost as lean mass was 17.3% +/- 27.8%
      and 37.5% +/- 14.6%, respectively (p = 0.03). CONCLUSION: Maintaining adequate
      protein intake may reduce lean mass losses associated with voluntary weight loss
      in older women.

PMID- 18810297
TI  - Senile anorexia in acute-ward and rehabilitations settings.
AB  - The most common pathological change in eating behaviour among older persons is
      anorexia, which accounts for a large percent of undernutrition in older adults.
      The main research aims are to determine, in a sample of acute and rehabilitation
      elderly subjects, the prevalence of anorexia of aging and the causes most
      impacting on senile anorexia. METHODS: four different Units cooperated to this
      research study. Patients were recruited from geriatric acute and rehabilitation
      wards in Italy. Each Research Unit, for the estimation of the prevalence of
      anorexia in elderly subjects evaluated all the patients aged over 65 recruited
      from April 2006 to June 2007. Nutritional status, depression, social, functional
      and cognitive status, quality of life, health status, chewing, swallowing,
      sensorial functions were evaluated in anorexic patients and in a sample of
      "normal eating" elderly subjects. RESULTS: 96 anorexic subjects were selected in
      acute and rehabilitation wards (66 women; 81.5 +/- 7 years; 30 men: 81.8 +/- 8
      years. The prevalence of anorexia in the sample was 33.3% in women and 26.7% in
      men. Anorexic subjects were older and more frequently needed help for shopping
      and cooking. A higher (although not statistically significant) level of
      comorbidity was present in anorexic subjects. These subjects reported
      constipation and epigastrium pain more frequently. Nutritional status parameters
      (MNA, anthropometry, blood parameters) were significantly worst in anorexic
      subjects whereas CRP was higher. Chewing and swallowing efficiencies were
      significantly impaired and eating patterns were different for anorexic subjects
      with a significant reduction of protein rich foods. CONCLUSIONS: consequences of
      anorexia can be extremely serious and deeply affect both patient's mobility,
      mortality and quality of life. Therefore, it is of utmost importance to perform a
      special evaluation of the nutritional risk, to constantly evaluate the
      nutritional status and feeding intake of older patients, to identify and treat
      the underlying disease when possible, to institute environmental and behavioural
      modifications, to organise staff better in order to produce higher quality
      feeding assistance during mealtimes, to plan early nutrition rehabilitation and
      nutritional education programs for caregivers. There is also the necessity to
      develop diagnostic procedures easy to perform, able to identify the pathogenesis
      of anorexia and, therefore, treatment strategies exactly fitting the patients'
      needs.

PMID- 18810299
TI  - Predicting early mortality among elderly patients hospitalised in medical wards
      via emergency department: the SAFES cohort study.
AB  - OBJECTIVES: The aim of the study was, by early identification of deleterious
      prognostic factors that are open to remediation, to be in a position to assign
      elderly patients to different mortality risk groups to improve management.
      DESIGN: Prospective multicentre cohort. SETTING: Nine French teaching hospitals.
      PARTICIPANTS: One thousand three hundred and six (1 306) patients aged 75 and
      over, hospitalised after having passed through Emergency Department (ED).
      MEASUREMENTS: Patients were assessed using Comprehensive Geriatric Assessment
      (CGA) tools. A Cox survival analysis was performed to identify prognostic
      variables for six-week mortality. Receiver Operating Characteristics analysis was
      used to study the discriminant power of the model. A mortality risk score is
      proposed to define three risk groups for six-week mortality. RESULTS: Crude
      mortality rate after a six week follow-up was 10.6% (n=135). Prognostic factors
      identified were: malnutrition risk (HR=2.1; 95% CI: 1.1-3.8; p=.02), delirium
      (HR=1.7; 95% CI: 1.2-2.5; p=.006), and dependency: moderate dependency (HR=4.9;
      95% CI: 1.5-16.5; p=.01) or severe dependency (HR=10.3; 95% CI: 3.2-33.1; p <
      .001). The discriminant power of the model was good: the c-statistic representing
      the area under the curve was 0.71 (95% IC: 0.67 - 0.75; p < .001). The six-week
      mortality rate increased significantly (p < .001) across the three risk groups:
      1.1% (n=269; 95% CI=0.5-1.7) in the lowest risk group, 11.1% (n=854; 95% CI=9.4
      12.9) in the intermediate risk group, and 22.4% (n=125; 95% CI=20.1-24.7) in the
      highest risk group. CONCLUSIONS: A simple score has been calculated (using only
      three variables from the CGA) and a practical schedule proposed to characterise
      patients according to the degree of mortality risk. Each of these three variables
      (malnutrition risk, delirium, and dependency) identified as independent
      prognostic factors can lead to a targeted therapeutic option to prevent early
      mortality.

PMID- 18810298
TI  - Prevention of progression to dementia in the elderly: rationale and proposal for
      a health-promoting memory consultation (an IANA Task Force).
AB  - Alzheimer's disease (AD) is the most frequent form of dementia and according to
      the most recent estimation it affects nearly 27 million people in the world. The
      onset of the disease is generally insidious. It is becoming increasingly evident
      that the underlying pathophysiological mechanisms are active long before the
      appearance of the clinical symptoms of the disease. In the current context, it is
      important to develop strategies to delay the onset of cognitive decline. Delaying
      the onset by 5 years would reduce the prevalence by half at term, and a delay of
      10 years would reduce it by three-quarters. The effectiveness of currently
      suggested preventive approaches remains to be confirmed, but certain strategies
      could be applied straight away to at-risk subjects. We propose that a health
      promoting memory consultation should be set up for elderly persons who have
      attended a specialized memory consultation and in whom the diagnosis of dementia
      and of AD in particular, has not been established by standardized tools. Through
      this consultation, they would be offered full multidimensional investigation of
      all aspects of their health status, follow-up could be organized, general
      practitioners in private practice could be made more conscious of this population
      and the elderly could be made more aware of the risk factors to which they are
      exposed. The development of an information policy for the elderly would meet a
      present need. In our reflection, we must take into account the question of how to
      give this preventive consultation its due place in the healthcare pathway of the
      elderly person in order to ensure coordinated follow-up with all the other health
      professionals involved. The principle of the health-promoting memory consultation
      is undergoing validation in a large French multicentre preventive trial in 1200
      frail elderly persons aged 70 years followed for three years, the Multidomain
      Alzheimer Preventive Trial (MAPT).

PMID- 18810300
TI  - Heavy metals in the farming environment and in some selected aquaculture species
      in the Van Phong Bay and Nha Trang Bay of the Khanh Hoa Province in Vietnam.
AB  - Aquaculture is currently one of the most rapidly growing production sectors in
      Vietnam. This publication describes the concentrations of heavy metals in the
      farming environment and some aquaculture species in the Khanh Hoa Province in
      Vietnam. The concentration of total As in the sediments ranged from 0.07 to 0.64
      mg/kg, whereas the concentration of Hg varied from <0.0005 to 0.56 mg/kg. The
      corresponding concentration span for Cd and Pb, were 0.001-0.069 and 0.016-0.078
      mg/kg, respectively. The concentrations of As in the aquaculture organisms
      spanned from 0.14 to 1.03 mg/kg. For Hg the concentrations varied from 0.1 to
      0.45 mg/kg, for Cd from 0.02 to 0.10 mg/kg and for Pb from 0.07 to 0.37 mg/kg.

PMID- 18810301
TI  - Pilot study utilizing a patient educational brochure at a vesicovaginal fistula
      hospital in Nigeria, Africa.
AB  - This paper presents a pilot study exploring the utility and feasibility of use of
      a vesicovaginal fistula (VVF) patient educational brochure. Women awaiting or
      recently having undergone VVF surgery examined a six-paneled educational brochure
      detailing the causes, treatment options, and prevention methods of VVF.
      Participants answered demographic questions and gave detailed responses to a
      questionnaire that addressed the brochure material. A convenience sample of 50
      patients, with a mean age of 26.1 years, participated. Universally, these women
      felt that the information they learned from the brochure was useful. Suggestions
      by participants regarding prevention of VVF included laboring in a hospital
      (80%), educating other women (30%), and discouraging early marriage (8%). Primary
      barriers to prevention and treatment included financial restraints (84%) and
      transportation difficulties (30%). The utilization of a simple, low-cost
      educational brochure has the ability to educate women on the causes, treatment,
      and prevention of VVF.

PMID- 18810302
TI  - Utilization of inpatient care before and after hip fracture: a population-based
      study.
AB  - SUMMARY: Evaluation of hospitalizations in a 70+ population showed that hip
      fractures (HF) were associated with a significant increase in the utilization of
      inpatient care for a lengthy period. Hospital days attributable to several
      diagnostic classes still exceeded both prefracture and population levels in the
      second year after HF. INTRODUCTION: The goal was to assess effects of HF on the
      inpatient care utilization. METHODS: The study covered HF patients and the
      70+general population (26,000) living in Central Finland. Hospitalization data
      categorized by the ICD-10 main classes were obtained from the nationwide
      discharge register. RESULTS: In 2002-2003, 498 residents (mean age 82 SD 7, 74.9%
      women) of the study area sustained HF. Among them, the number of hospital days
      was 23, 107, and 52 per person-year in the prefracture, first and second
      postfracture year, respectively. In the 70+ general population, the number was
      constantly 11 per year. The age- and gender-adjusted rate ratio of hospital days
      between the two groups was 1.30 (95% CI 1.27 to 1.32), 6.91 (95% CI 6.85 to
      7.00), and 3.61 (95% CI 3.55 to 3.67) for the prefracture, first and second
      postfracture year, respectively. Hospital days due to injuries were more
      prevalent in the HF group throughout the period. Moreover, excess of days was
      seen in six other diagnostic classes in the first and in four classes in the
      second postfracture year. CONCLUSIONS: Hospital days in HF patients still
      exceeded both the prefracture and population levels in the second year after HF.
      Days attributable to several other causes than HF itself became also more
      prevalent indicating that HF can steeply decrease patients' coping capacity and
      launch a cascade of impairments in the function of different organ systems.

PMID- 18810303
TI  - Genetic and environmental determinants on bone loss in postmenopausal Caucasian
      women: a 14-year longitudinal twin study.
AB  - SUMMARY: This longitudinal twin study documented that genetic factors explain 44
      56% of the between-individual variance in bone loss at femoral neck, lumbar
      spine, and forearm in postmenopausal Caucasian women, providing a rationale for
      identifying the specific genes involved. INTRODUCTION: Although there is a
      significant genetic effect on peak BMD, until recently, no substantive studies on
      heritability of bone loss in human were available. The aim of the study was to
      estimate the heritability of the bone loss at multiple sites in postmenopausal
      Caucasian women. METHODS: Postmenopausal female monozygotic (MZ) and dizygotic
      (DZ) twins aged 40 or above at baseline were selected from the TwinsUK registry
      and followed up for an average of 8 years (range 5-14 years). All twins were
      noncurrent hormone replacement therapy users and not on any osteoporosis
      treatment. They had dual-energy X-ray absorptiometry (DXA) scans of their hip,
      lumbar spine, and forearm several times (range 2-9) during the follow-up period.
      Individual bone losses at femoral neck, lumbar spine, and forearm were estimated
      by linear regression modeling. Structural equation modeling was utilized to
      estimate the heritability of the bone loss. RESULTS: A total of 712
      postmenopausal Caucasian female twins (152 MZ and 204 DZ pairs) were included. MZ
      twins were older and had slightly lower BMD at all sites than DZ twins. DZ twins
      had slightly higher bone loss at lumbar spine, but similar at femoral neck and
      forearm compared to MZ twins. Intraclass correlation coefficients (ICC) for the
      bone loss at all sites were significantly higher in MZ than DZ twin pairs (p =
      0.0045, 0.0003, and 0.0007 for femoral neck, lumbar spine, and forearm,
      respectively), indicating a significant genetic influence on bone loss at these
      sites. After adjustment for age at baseline and weight change during the follow
      up, the heritability estimate was 47% (95% CI 27-63%) for bone loss at femoral
      neck, 44% (95% CI 27-58%) for lumbar spine, and 56% (95% CI 44-65%) for forearm.
      CONCLUSIONS: Our data suggest that up to 56% of the between-individual variance
      in bone loss is due to genes, providing a rationale to identify specific genetic
      factors for bone loss.

PMID- 18810304
TI  - Investigation of interaction between DCDC2 and KIAA0319 in a large German
      dyslexia sample.
AB  - The dyslexia susceptibility locus DYX2 (chr. 6p21-p22) harbours two candidate
      genes, DCDC2 and KIAA0319. In 2006, Harold et al. reported evidence for
      interaction between both genes. Having previously identified a risk haplotype for
      dyslexia in DCDC2, but not KIAA0319, in German families, we also tested for
      interaction between this risk haplotype and KIAA0319. We found a nominally
      significant association for the quantitative dimension "word reading", the core
      phenotype in the study of Harold et al., which may be considered as supportive
      evidence.

PMID- 18810305
TI  - Strategies for reducing test anxiety and optimizing exam preparation in German
      university students: a prevention-oriented pilot project of the University of
      Wurzburg.
AB  - Test anxiety is a significant problem among university students which is
      frequently accompanied by a decline in performance and severe psychological
      problems. Studies of treatment methods of test anxiety were identified using
      literature searches of the Cochrane Library database of randomized controlled
      trials. A variety of intervention techniques for the treatment of test anxiety
      was detected, from which cognitive behavioral methods were found to be most
      effective for the treatment of test anxiety. According to empirical findings,
      university students should be taught strategies to cope with the demands and
      organization of their studies at a very early stage to prevent test anxiety and
      its concomitants. The University of Wurzburg (Germany) started a pilot project in
      fall 2007 comprising lectures and peer coaching with the aim to optimize learning
      skills and exam preparation to prevent test anxiety. The evaluation of the
      present concept showed a high level of acceptance among students.

PMID- 18810306
TI  - Mitochondrial DNA haplogroups and subhaplogroups are associated with Parkinson's
      disease risk in a Polish PD cohort.
AB  - mtDNA common variation is inconsistently reported to modify the risk of
      Parkinson's disease (PD). We evaluated the impact of the mitochondrial
      haplogroups, subhaplogroups, coding and non-coding single-nucleotide
      polymorphisms on PD risk in 241 PD patients and 277 control subjects. After
      stratification by gender, we found that haplogroup J (OR 0.19; 95% CI 0.069-0.53;
      P = 0.0014) was associated with a lower PD risk in males. Unexpectedly,
      subhaplogroup analysis based on the control region (CR) polymorphisms
      demonstrated that subcluster K1a was more prevalent in healthy controls, while
      K1c was more frequent in PD patients (P = 0.025 and P = 0.011, respectively; two
      tailed Fisher's exact test). Additionally, we confirmed the hypothesis that
      sublineages (U4 + U5a1 + K+J1c + J2), previously proposed to partially uncouple
      oxidative phosphorylation (OXPHOS), decrease PD risk (P = 0.027, chi2 with Yates'
      correction). The putative protective effect of uncoupling mtDNAs against PD might
      result from decreased production of reactive oxygen species. We propose that
      stratification into subhaplogroups or by gender could be necessary to reveal the
      involvement of specific mtDNA sublineages in PD pathogenesis.

PMID- 18810307
TI  - Comparison of combined psycho- and pharmacotherapy with monotherapy in anxiety
      disorders: controversial viewpoints and clinical perspectives.
AB  - Anxiety disorders are among the most frequent psychiatric disorders. Experimental
      evidence supports both psychotherapy as well as pharmacotherapy as effective
      treatments. There is, however, a controversy concerning the efficacy of a
      combination of both approaches. While some studies suggest that combined
      treatment enhances efficacy, others report conflicting results. This article
      traces the positions in this debate. We present the results from two recent meta
      analyses and discuss implications for clinical practice and further research. We
      suggest that a research strategy that strives to establish differential
      indications based on patient characteristics should be preferred over attempts to
      reach a global judgement of the question, which appears too simplistic given the
      complexity of the issue.

PMID- 18810308
TI  - G6PD deficiency in autism: a case-series from Saudi Arabia.
AB  - Autism is a neurodevelopmental disorder characterized by a pattern of social and
      communication deficits. Although it occurs in all cultures and countries, most of
      the published research has come from Western industrialized countries. In
      particular, relatively little is known about its clinical correlates and
      comorbidity in African and Middle Eastern countries. In this paper, we report two
      cases of G6PD deficiency with autism, recruited as part of a larger study on the
      occurrence of autism in Saudi Arabia. These findings suggest that a different set
      of medical conditions may be associated with autism in developing countries.

PMID- 18810309
TI  - Fathers' parenting, adverse life events, and adolescents' emotional and eating
      disorder symptoms: the role of emotion regulation.
AB  - PURPOSE: To investigate the role of emotion regulation in the relation between
      fathers' parenting (specifically warmth, behavioral control and psychological
      control) and adolescents' emotional and eating disorder symptoms, after
      adjustment for controls. METHODS: A total of 203 11-18 year-old students from a
      school in a socio-economically disadvantaged area in North-East London completed
      questionnaires assessing emotional symptoms (measured with the Strengths and
      Difficulties Questionnaire's (SDQ) Emotional Symptoms Scale), eating disorder
      symptoms (measured with the Eating Attitudes Test (EAT-26)), difficulties in
      emotion regulation (measured with the Difficulties in Emotion Regulation Scale
      (DERS)), and fathers' overprotection and warmth, measured with the Parental
      Bonding Instrument (PBI), as well as behavioral and psychological control. The
      confounding variables considered were number of proximal (i.e., during the last
      year) adverse life events experienced, gender, age, and socio-economic status
      (eligibility for free school meals). RESULTS: Adolescents' difficulties in
      emotion regulation mediated the link between fathers' psychological control and
      adolescents' emotional symptoms, but not the link between fathers' parenting and
      adolescents' eating disorder symptoms, which appeared to be more directly linked
      to fathers' psychological control and number of proximal adverse life events
      experienced. Proximal adverse life events experienced were also strongly
      associated with difficulties in emotion regulation. CONCLUSIONS: The study
      findings have implications for intervention programs which may prove more
      fruitful in addressing adolescent emotional problems by targeting underlying
      emotion regulation abilities, and in addressing adolescent eating disorder
      symptoms by protecting adolescents with a recent experience of multiple adverse
      life events. Parenting programs also stand to benefit from the evidence presented
      in this study that paternal psychological control may have uniquely harmful
      consequences for adolescent development through the hampering or atrophying of
      emotion regulation abilities and the encouragement of eating disorders.

PMID- 18810310
TI  - Everyday social and conversation applications of theory-of-mind understanding by
      children with autism-spectrum disorders or typical development.
AB  - Children with autism-spectrum disorders (ASD) often fail laboratory false-belief
      tests of theory of mind (ToM). Yet how this impacts on their everyday social
      behavior is less clear, partly owing to uncertainty over which specific everyday
      conversational and social skills require ToM understanding. A new caregiver
      report scale of these everyday applications of ToM was developed and validated in
      two studies. Study 1 obtained parent ratings of 339 children (85 with autism; 230
      with Asperger's; 24 typically-developing) on the new scale and results revealed
      (a) that the scale had good psychometric properties and (b) that children with
      ASD had significantly more everyday mindreading difficulties than typical
      developers. In Study 2, we directly tested links between laboratory ToM and
      everyday mindreading using teacher ratings on the new scale. The sample of 25
      children included 15 with autism and 10 typical developers aged 5-12 years.
      Children in both groups who passed laboratory ToM tests had fewer everyday
      mindreading difficulties than those of the same diagnosis who failed. Yet,
      intriguingly, autistic ToM-passers still had more problems with everyday
      mindreading than younger typically-developing ToM-failers. The possible roles of
      family conversation and peer interaction, along with ToM, in everyday social
      functioning were considered.

PMID- 18810311
TI  - Predictive factors of length of inpatient treatment in anorexia nervosa.
AB  - OBJECTIVE: To identify clinical variables influencing the length of stay (LOS) of
      inpatient treatment for anorexia nervosa (AN). METHOD: We analyzed structured
      clinical charts of 300 consecutive hospitalizations for AN in a specialized
      eating disorder unit. The sample included patients from 12 to 22 years old.
      Factors related to the patient and events occurring during the stay were
      investigated as possible predictors of LOS. RESULTS: Mean LOS was 135 days. The
      best model of linear regression revealed that the following factors were
      significantly related to LOS: duration of AN at admission, use of tube feeding
      during the stay, accomplishment of the therapeutic weight contract and presence
      of a comorbid disorder. CONCLUSIONS: The identification of factors influencing
      duration of stay, both at the outset and during the hospitalization, could help
      clinicians to optimize and individualize treatments, as well as increase patient
      and family compliance.

PMID- 18810312
TI  - Mental health and quality of life in deaf pupils.
AB  - In the past decade, the living conditions of hearing impaired children have been
      changing due to new technologies and mainstreaming in schools. The majority of
      population-based studies in deaf pupils were conducted before these changes
      started to take place. The present study aimed to evaluate the current situation
      regarding aspects of mental health and, for the first time, quality of life in a
      representative sample of deaf pupils. The sample stems from a population of
      145,000 pupils attending the first to ninth grades during the school years 2003
      2005 in Upper Austria. From 186 children with bilateral hearing impairment of at
      least 40 dB registered at the centre for special education for children with
      sensory impairments, 99 with a performance IQ above 70 were included in the
      present study. Parents and teachers completed the strengths and difficulties
      questionnaire (SDQ), while parents and children were administered the inventory
      for the assessment of the quality of life in children and adolescents (ILC).
      Results indicated that deaf children scored significantly higher on the SDQ than
      their counterparts from normative samples according to both parent and teacher
      ratings. Differences were most marked with regard to conduct problems, emotional
      problems, and peer problems, and less marked for hyperactivity/inattention. While
      parents of deaf children had a generally positive view of their children's
      quality of life, deaf children provided a more complex picture, stressing areas
      of dissatisfaction. Mental health and quality of life were found to be unrelated
      to the child's degree of deafness.

PMID- 18810313
TI  - An adult case of Henoch-Schonlein purpura complicating common peroneal nerve
      mononeuropathy.
AB  - We present an adult patient with Henoch-Schonlein Purpura who developed
      mononeuropathy in the common peroneal nerve. Upon admission, the patient had
      palpable purpura in the arms and legs, polyarthralgia, abdominal pain, and
      leukocytoclastic vasculitis in the skin biopsy. These symptoms disappeared with
      30 mg daily of oral prednisolone. One month later, after induction therapy,
      fever, livedo reticularis and peripheral mononeuropathy developed with
      hypocomplementemia and the patient was treated successfully with glucocorticoid
      pulse therapy.

PMID- 18810314
TI  - The timing of ovulation with respect to sexual swelling detumescence in wild
      olive baboons.
AB  - Baboon researchers commonly use the timing of sexual swelling detumescence to
      infer the timing of ovulation. These estimates are then used for a variety of
      purposes, including the interpretation of male and female behaviour, assessment
      of likely paternity, and the calculation of gestation lengths. Although captive
      studies have measured the timing of ovulation with respect to detumescence, this
      has not been measured in wild baboons. Here, we use observational data on female
      sexual swellings, and hormonal data measured from faeces, to investigate the
      timing of ovulation with respect to detumescence in wild olive baboons. Our data
      show similar variability in the timing of ovulation with respect to detumescence
      as that produced by captive studies, although there are some notable differences,
      including the absence of any ovulations measured on or after the day of swelling
      detumescence. We discuss the importance of our results for baboon researchers
      using swellings to infer ovulation as part of their studies.

PMID- 18810315
TI  - An often unrecognized cause of thunderclap headache: reversible cerebral
      vasoconstriction syndrome.
AB  - Thunderclap headache (TCH) can have several causes of which subarachnoid
      hemorrhage (SAH) is most common and well known. A rare cause of TCH is the
      reversible cerebral vasoconstriction syndrome (RCVS) which is characterized by a
      reversible segmental vasoconstriction of the intracranial vessels. We describe
      two patients with TCH due to RCVS and the probable precipitating factor, namely,
      cannabis and an anti-migraine drug. In RCVS, cerebrospinal fluid examination is
      (near) normal, in contrast to SAH and (primary) cerebral vasculitis. Brain MRI
      may be normal or shows infarction. MRA can demonstrate vasoconstriction of the
      great arteries, but a normal MRA does not rule out the diagnosis. Caliber changes
      on cerebral angiography cannot adequately differentiate between RCVS and
      vasculitis. Calcium-channel antagonists may be a good therapy and repeated
      transcranial Doppler ultrasonography can be a reliable non-invasive investigation
      to monitor the effect of treatment and demonstrate reversibility of the
      vasoconstriction.

PMID- 18810316
TI  - Sporadic hemiplegic migraine: report of a case with clinical and radiological
      features.
AB  - A case of visual hallucination, headache and left hemiparesis is reported. The
      patient had a history of recurrent attacks of similar semiology for the previous
      15 years. MRI brain revealed a cortical hyperintensity on T2W, FLAIR and
      diffusion weighted imaging (DWI) in the right cerebral hemisphere with a normal
      ADC (apparent diffusion coefficient) map and MR angiogram. Detailed workup for
      MELAS was negative. A diagnosis of sporadic hemiplegic migraine was made and he
      was managed conservatively. He made a gradual complete recovery over 2 weeks. He
      was discharged on flunarizine for prophylaxis and has remained asymptomatic over
      the ensuing 4 months. This interesting condition is reviewed and discussed
      herein.

PMID- 18810317
TI  - Roles of the major apoptotic nuclease-DNA fragmentation factor-in biology and
      disease.
AB  - It has now been more than ten years since the discovery of the major apoptotic
      nuclease, DNA fragmentation factor (DFF), also known as caspase-activated DNase
      (CAD). Here we review the recent literature that has uncovered new insight into
      DFF's regulation, and both its positive and negative roles in human disease.
      Cells from mice deficient in DFF still undergo apoptotic death without
      significant cell-autonomous DNA degradation. Their corpses' genomes are
      subsequently degraded by lysosomal DNase II after phagocytosis. However,DFF
      deficient mice are more susceptible to cancer. Indeed, several different cancers
      in humans are associated with defects in DFF expression and it has been proposed
      that DFF is a p53-independent tumor suppressor. Negative aspects of DFF
      expression include contributing to susceptibility to acquire systemic lupus
      erythematosus, to chromosomal translocations that result in mixed lineage
      leukemias, and in the possible spreading of oncogenes and HIV due to horizontal
      gene transfer.

PMID- 18810318
TI  - Origin of pancreatic endocrine cells from biliary duct epithelium.
AB  - We describe an explant culture system to study the formation of pancreatic-type
      endocrine cells by the biliary tract. In this model, beta-cells and other
      endocrine cells appear in the biliary duct epithelium and their number increases.
      Evidence for an origin from the duct epithelium is threefold. Firstly,
      differentiating cells transiently co-express insulin and bind Dolichos lectin.
      Secondly, beta-cells in cultures isolated from Alb-Cre-R26R-LacZ mice are beta
      galactosidase positive. Thirdly, co-culture of biliary epithelium and ROSA26
      pancreatic buds shows that endocrine cells do not migrate from the pancreas. The
      expression of the pancreatic transcription factors Pdx1, HNF6 and Sox9 is
      widespread, as is Hes1, which represses endocrine development, while that of
      Ngn3, which is a proendocrine transcription factor, is transient, consistent with
      an early stage of endocrine cell differentiation. Nicotinamide will increase the
      number of beta-cells formed, while EGF+LIF completely inhibits their formation.

PMID- 18810319
TI  - Phosphatidylinositol 3-kinase-dependent transcriptional silencing of the
      translational repressor 4E-BP1.
AB  - The suppressor of translation initiation 4E-BP1 functions as a key regulator in
      cellular growth, differentiation, apoptosis and survival. While the control of 4E
      BP1 activity via phosphorylation has been widely studied, the molecular
      mechanisms and the signaling pathways that govern 4E-BP1 gene expression are
      largely unknown. Here we show that inactivation of phosphatidylinositol 3-kinase
      (PI3K) consequent to stable expression of the antiproliferative somatostatin
      receptor 2 (sst2) in pancreatic cancer cells leads to transcriptional
      accumulation of the hypophosphorylated forms of 4E-BP1 protein. In cancer cells,
      while 4E-BP1 gene promoter is maintained repressed in a PI3K-dependent mechanism,
      sst2-dependent inactivation of the PI3K/Akt pathway releases 4E-BP1 gene
      transcription. Furthermore, the use of a pharmacological inhibitor and dominant
      negative or -positive mutants of PI3K all affect 4E-BP1 protein expression and
      promoter activity in different cell lines. These data show that, in addition to
      inactivation of 4E-BP1 via hyperphosphorylation, signaling through the PI3K
      pathway silences 4E-BP1 gene transcription.

PMID- 18810320
TI  - The peroxisomal protein import machinery--a case report of transient
      ubiquitination with a new flavor.
AB  - The peroxisomal protein import machinery displays remarkable properties. Be it
      its capacity to accept already folded proteins as substrates, its complex
      architecture or its energetics, almost every aspect of this machinery seems
      unique. The list of unusual properties is still growing as shown by the recent
      finding that one of its central components, Pex5p, is transiently
      monoubiquitinated at a cysteine residue. However, the data gathered in recent
      years also suggest that the peroxisomal import machinery is not that exclusive
      and similarities with p97/Cdc48-mediated processes and with multisubunit RING-E3
      ligases are starting to emerge. Here, we discuss these data trying to distill the
      principles by which this complex machinery operates.

PMID- 18810321
TI  - Proteinases in cutaneous wound healing.
AB  - Cutaneous wound healing is a complex and highly coordinated process where a
      number of different cell types participate to renew the damaged tissue under the
      strict regulation of soluble and insoluble factors. One of the most versatile
      processes involved in wound repair is proteolysis. During cell migration,
      proteins of extracellular matrix are cleaved, often creating biologically active
      cleavage products, and proteolysis of cellular contacts leads to increased cell
      motility and division. Moreover, proteases activate various growth factors and
      other proteases in wound and regulate growth factor signaling by shedding growth
      factor receptors on cell surface. Normally, proteolysis is strictly controlled,
      and changes in protease activity are associated with alterations in wound closure
      and scar formation. Here, we present the current view on the role of
      metalloproteinases and the plasmin-plasminogen system in normal and aberrant
      cutaneous wound repair and discuss their role as potential therapeutic targets
      for chronic ulcers or fibrotic scars.

PMID- 18810322
TI  - Crystallin proteins and amyloid fibrils.
AB  - Improper protein folding (misfolding) can lead to the formation of disordered
      (amorphous) or ordered (amyloid fibril) aggregates. The major lens protein, alpha
      crystallin, is a member of the small heat-shock protein (sHsp) family of
      intracellular molecular chaperone proteins that prevent protein aggregation.
      Whilst the chaperone activity of sHsps against amorphously aggregating proteins
      has been well studied, its action against fibril-forming proteins has received
      less attention despite the presence of sHsps in deposits found in fibril
      associated diseases (e.g. Alzheimer's and Parkinson's). In this review, the
      literature on the interaction of alphaB-crystallin and other sHsps with fibril
      forming proteins is summarized. In particular, the ability of sHsps to prevent
      fibril formation, their mechanisms of action and the possible in vivo
      consequences of such associations are discussed. Finally, the fibril-forming
      propensity of the crystallin proteins and its implications for cataract formation
      are described along with the potential use of fibrillar crystallin proteins as
      bionanomaterials.

PMID- 18810323
TI  - A bee-line into learning and memory mechanisms.

PMID- 18810324
TI  - Syncoilin, an intermediate filament-like protein linked to the dystrophin
      associated protein complex in skeletal muscle.
AB  - Syncoilin is a member of the intermediate filament protein family, highly
      expressed in skeletal and cardiac muscle. Syncoilin binds alpha-dystrobrevin, a
      component of the dystrophin associated protein complex (DAPC) located at the
      muscle cell membrane, and desmin, a muscle-specific intermediate filament
      protein, thus providing a link between the DAPC and the muscle intermediate
      filament network. This link may be important for muscle integrity and force
      transduction during contraction, a theory that is supported by the reduced force
      generating capacity of muscles from syncoilin-null mice. Additionally, syncoilin
      is found at increased levels in the regenerating muscle fibres of patients with
      muscular dystrophies and mouse models of muscle disease. Therefore, syncoilin may
      be important for muscle regeneration in response to injury. The aims of this
      article are to review current knowledge about syncoilin and to discuss its
      possible functions in skeletal muscle.

PMID- 18810325
TI  - AMP-activated protein kinase in skeletal muscle: from structure and localization
      to its role as a master regulator of cellular metabolism.
AB  - The AMP-activated protein kinase (AMPK) is a metabolite sensing serine/threonine
      kinase that has been termed the master regulator of cellular energy metabolism
      due to its numerous roles in the regulation of glucose, lipid, and protein
      metabolism. In this review, we first summarize the current literature on a number
      of important aspects of AMPK in skeletal muscle. These include the following: (1)
      the structural components of the three AMPK subunits (i.e. AMPKalpha, beta, and
      gamma), and their differential localization in response to stimulation in muscle;
      (2) the biochemical regulation of AMPK by AMP, protein phosphatases, and its
      three known upstream kinases, LKB1, Ca2+/calmodulin-dependent protein kinase
      kinase (CaMKK), and transforming growth factor-beta-activated kinase 1 (TAK1);
      (3) the pharmacological agents that are currently available for the activation
      and inhibition of AMPK; (4) the physiological stimuli that activate AMPK in
      muscle; and (5) the metabolic processes that AMPK regulates in skeletal muscle.

PMID- 18810326
TI  - Evaluation of MR markers that predict survival in patients with newly diagnosed
      GBM prior to adjuvant therapy.
AB  - Purpose Glioblastoma Multiforme (GBM) is the most common and lethal primary brain
      tumor in adults. The goal of this study was to test the predictive value of MR
      parameters in relation to the survival of patients with newly diagnosed GBM who
      were scanned prior to receiving adjuvant radiation and chemotherapy. Methods The
      study population comprised 68 patients who had surgical resection and were to be
      treated with fractionated external beam radiation therapy and chemotherapy.
      Imaging scans included anatomical MRI, diffusion and perfusion weighted imaging
      and (1)H MRSI. The MR data were acquired 3-5 weeks after surgery and
      approximately 1 week before treatment with radiation therapy. The diffusion,
      perfusion and spectroscopic parameter values were quantified and subjected to
      proportional hazards analysis that was adjusted for age and scanner field
      strength. Results The patients with larger lesion burden based upon volumes of
      anatomic lesions, volume of CNI2 (number of voxels within the T2 lesion having
      choline to NAA index >2), volume of CBV3 (number of pixels within the T2 lesion
      having relative cerebral blood volume >3), and volume of nADC1.5 (number of
      pixels within the T2 lesion having normalized apparent diffusion coefficient
      <1.5) had a higher risk for poor outcome. High intensities of combined measures
      of lactate and lipid in the T2 and CNI2 regions were also associated with poor
      survival. Conclusions Our study indicated that several pre-treatment anatomic,
      physiological and metabolic MR parameters are predictive of survival. This
      information may be important for stratifying patients to specific treatment
      protocols and for planning focal therapy.

PMID- 18810327
TI  - Solubility, stability, physicochemical characteristics and in vitro ocular tissue
      permeability of hesperidin: a natural bioflavonoid.
AB  - PURPOSE: Hesperidin holds potential in treating age-related macular degeneration,
      cataract and diabetic retinopathy. The aim of this study, constituting the first
      step towards efficient ocular delivery of hesperidin, was to determine its
      physicochemical properties and in vitro ocular tissue permeability. METHODS: pH
      dependent aqueous solubility and stability were investigated following standard
      protocols. Permeability of hesperidin across excised rabbit cornea, sclera, and
      sclera plus retinal pigmented epithelium (RPE) was determined using a side-bi
      side diffusion apparatus. RESULTS: Hesperidin demonstrated poor, pH independent,
      aqueous solubility. Solubility improved dramatically in the presence of 2
      hydroxypropyl-beta-cyclodextrin (HP-beta-CD) and the results supported 1:1
      complex formation. Solutions were stable in the pH and temperature (25, 40
      degrees C) conditions tested, except for samples stored at pH 9. Transcorneal
      permeability in the apical-basal and basal-apical directions was 1.11 +/- 0.86 x
      10(-6) and 1.16 +/- 0.05 x 10(-6) cm/s, respectively. The scleral tissue was more
      permeable (10.2 +/- 2.1 x 10(-6) cm/s). However, permeability across
      sclera/choroid/RPE in the sclera to retina and retina to sclera direction was
      0.82 +/- 0.69 x 10(-6), 1.52 +/- 0.78 x 10(-6) cm/s, respectively, demonstrating
      the barrier properties of the RPE. CONCLUSION: Our results suggest that stable
      ophthalmic solutions of hesperidin can be prepared and that hesperidin can
      efficiently permeate across the corneal tissue. Further investigation into its
      penetration into the back-of-the eye ocular tissues is warranted.

PMID- 18810328
TI  - PK/PD modelling and beyond: impact on drug development.
AB  - PK/PD modelling will play an increasingly important role in drug development,
      because it will identify key properties of a drug in vivo, allowing the
      characterization and prediction of the time course of drug effects under
      physiological and pathological conditions (intensity and duration). It has
      developed from a descriptive to a mechanism-based approach, taking the relevant
      processes on the causal path between drug administration and drug effect into
      account. Recent developments and insights from systems biology and systems
      pharmacology will provide new information on the complexities of disease
      associated with the identification of multiple targets for drug treatment. This
      will give rise to new opportunities of drug combinations, which can only be
      developed rationally through the appropriate application of dynamical systems
      based PK/PD models.

PMID- 18810329
TI  - Thermolabile duplex-specific nuclease.
AB  - Using random mutagenesis of the gene encoding duplex-specific nuclease from the
      king crab we found a new mutant that retained all properties of the wild-type
      protein, but exhibited a much lower thermal stability. This enzyme, denoted
      thermolabile duplex-specific nuclease (DSN-TL), exhibits high processivity and
      selective cleavage of dsDNA. The inactivation temperature for DSN-TL is 15-20
      degrees C lower than that of the widely used DNase I and shrimp nuclease, and its
      catalytic activity is more than 10 times higher. Moreover, DSN-TL is resistant to
      proteinase K treatment. These properties make DSN-TL very useful for removing
      genomic DNA from RNA samples intended for quantitative RT-PCR.

PMID- 18810330
TI  - Construction of plasmids suitable for in vitro synthesis of full-length mRNAs
      having a 3'-poly(A)+tail.
AB  - In vitro synthesized mRNAs are often used as calibrants in gene expression
      analysis. In the case of an analytical procedure for gene expression containing a
      process of reverse transcription such as microarray analysis, full-length mRNAs
      having a 3'-poly(A)+tail are required as calibrants. However, the preparation of
      full-length mRNAs having a 3'-poly(A)+tail by using ordinary plasmid vectors is
      difficult. In this study, we established two plasmid vectors in which the
      nucleotide sequence corresponding to the 3'-poly(A)+tail were included. By simply
      inserting full-length cDNAs lacking their 3'-poly(A)+tail into established
      plasmid vectors, full-length mRNAs having a 3'-poly(A)+tail were successfully
      prepared.

PMID- 18810331
TI  - Sodium tungstate on some biochemical parameters of the parotid salivary gland of
      streptozotocin-induced diabetic rats: a short-term study.
AB  - Several studies have shown the antidiabetic properties of sodium tungstate. In
      this study, we evaluated some biochemical parameters of the parotid salivary
      gland of streptozotocin-induced diabetic rats treated with sodium tungstate
      solution (2 mg/ml). The studied groups were: untreated control (UC), treated
      control (TC), untreated diabetic (UD), and treated diabetic (TD). After 2 and 6
      weeks of treatment, parotid gland was removed and total protein and sialic acid
      (free and total) concentration and amylase and peroxidase activities were
      determined. Data were compared by variance analysis and Tukey test (p < 0.05).
      The sodium tungstate treatment modestly decreased the glycemia of streptozotocin
      induced diabetic rats. At week 2 of the study, parotid gland of diabetic rats
      presented a reduction of total protein concentration (55%) and an increase of
      amylase (120%) and peroxidase (160%) activities, free (150%) and total (170%)
      sialic acid concentration. No alteration in the evaluated parameters at week 6 of
      the study was observed. Sodium tungstate presented no significant effect in
      parotid gland. Our results suggest that diabetes causes initial modification in
      biochemical composition of parotid. However, this gland showed a recovery
      capacity after 6 week of the experimental time. Sodium tungstate has no effect in
      peripheral tissues, such as salivary glands.

PMID- 18810332
TI  - Zinc, manganese, calcium, copper, and cadmium level in scalp hair samples of
      schizophrenic patients.
AB  - The purpose of the study was to determine the concentration of trace elements
      present in scalp hair sample of schizophrenic patients and to find out the
      relationship between trace elements level and nutritional status or socioeconomic
      factors. The study was conducted among 30 schizophrenic male patients and 30
      healthy male volunteers. Patients were recruited from Bangabandhu Sheikh Mujib
      Medical University by random sampling. Hair trace element concentrations were
      determined by flame atomic absorption spectroscopy and analyzed by independent t
      test, Pearson's correlation analysis, regression analysis, and analysis of
      variance (ANOVA). Mn, Zn, Ca, Cu, and Cd concentrations of schizophrenic patients
      were 3.8 +/- 2.31 microg/gm, 171.6 +/- 59.04 microg/gm, 396.23 +/- 157.83
      microg/gm, 15.40 +/- 5.68 microg/gm, and 1.14 +/- 0.89 microg/gm of hair sample,
      while those of control subjects were 4.4 +/- 2.32 microg/gm, 199.16 +/- 27.85
      microg/gm, 620.9 +/- 181.55 microg/gm, 12.23 +/- 4.56 microg/gm, and 0.47 +/-
      0.32 microg/gm of hair sample, respectively. The hair concentration of Zn and Ca
      decreased significantly (p = 0.024; p = 0.000, respectively) and the
      concentration of Cu and Cd increased significantly (p = 0.021; p = 0.000,
      respectively) in schizophrenic patients while the concentration of Mn (p = 0.321)
      remain unchanged. Socioeconomic data reveals that most of the patients were poor,
      middle-aged and divorced. Mean body mass indices (BMIs) of the control group
      (22.26 +/- 1.91 kg/m(2)) and the patient group (20.42 +/- 3.16 kg/m(2)) were
      within the normal range (18.5-25.0 kg/m(2)). Pearson's correlation analysis
      suggested that only Ca concentration of patients had a significant positive
      correlation with the BMI (r = 0.597; p = 0.000) which was further justified from
      the regression analysis (R (2) = 44%; t = 3.59; p = 0.002) and one-way ANOVA test
      (F = 3.62; p = 0.015). A significant decrease in the hair concentration of Zn and
      Ca as well as a significant increase in the hair concentration of Cu and Cd in
      schizophrenic patients than that of its control group was observed which may
      provide prognostic tool for the diagnosis and treatment of this disease. However,
      further work with larger population is suggested to examine the exact correlation
      between trace element level and the degree of disorder.

PMID- 18810333
TI  - Estimation of toxic metals in scalp hair samples of chronic kidney patients.
AB  - The determination of toxic metals (TMs) in the biological samples of human beings
      is an important clinical screening procedure. The aim of this work is to
      determine total content of TMs, aluminum (Al), cadmium (Cd), nickel (Ni), and
      lead (Pb) in scalp hair samples of chronic kidney male patients (CKPs) on
      maintenance hemodialysis, during the period of 2005-2007. The study included 115
      CKPs (all smokers) and 150 controls or referents [82 (nonsmokers) and 68
      (smokers)]. Both controls and patients (males) were of the same age group (ranged
      25-55 years), socioeconomic status, localities, and dietary habits. The scalp
      hair samples were analyzed by electrothermal atomic absorption spectrometer,
      prior to microwave-induced acid digestion. The accuracy of the total Al, Cd, Ni,
      and Pb measurements was tested by simultaneously analyzing certified reference
      material (human hair NCS ZC81002). No significant differences were observed
      between the analytical results and the certified values (paired t test at p >
      0.05). The levels of TMs in scalp hair samples of patients were found to be
      higher as compared to control nonsmoker and smokers. Moreover, the study shows
      that levels of Al, Cd, Ni, and Pb in scalp hair samples may be useful to evaluate
      the impact of cigarette smoking in kidney failure patients.

PMID- 18810334
TI  - Innate immune recognition of nucleic acids.
AB  - The innate immune system employs a number of pattern recognition receptor
      families in response to DNAs and RNAs, either from invading microbes or within
      the hosts. These include the Toll-like receptors (TLRs), the retinoic acid
      inducible gene I (RIG-I) like receptors (RLRs), and the nucleotide-binding domain
      leucine-rich repeat/NOD-like receptor (NLRs), among other potential sensors in
      the cytoplasm. These receptors are composed of modular domain architecture, with
      ligand binding/sensing domains and signaling domains regulated either through
      dimerization/oligomerization, or conformational changes directed by enzymatic
      activities. Signaling pathways from different families of receptors converge on
      their respective common adapter proteins and lead to activation of transcription
      factors or caspases. Many of these receptors induce orchestrated responses to
      similar ligands from different cell types, resulting in redundant and
      complementary immunity to infections. This highly efficient defense system is a
      double-edged sword: inappropriate reaction to host ligands leads to compromised
      innate tolerance and autoimmune diseases. Structural studies of innate immune
      receptors and their signaling pathways are essential in our understanding of
      pattern recognition mechanisms and design of more efficient vaccine adjuvants.

PMID- 18810335
TI  - Understanding B cell activation: from single molecule tracking, through Tolls, to
      stalking memory in malaria.
AB  - B lymphocyte activation is initiated by the binding of antigens to the clonally
      expressed B cell receptors (BCRs) triggering signaling cascades that lead to the
      transcription of a variety of genes associated with B cell activation. Provided
      with the appropriate T cell help and the microenvironment of germinal centers
      antigen drives B cells to proliferate and differentiate into long-lived plasma
      cells and memory B cells that together constitute immunological memory. Here I
      describe efforts in my laboratory to gain an understanding of the cellular and
      molecular mechanisms that underlie three processes central to B cell biology
      namely, the initiation of BCR signaling, the interactions of the BCR with the
      innate immune system Toll-like receptors, and the generation and maintenance of B
      cell memory. Such knowledge is likely to aid research efforts in two areas of
      high public health priority, namely, the development of new therapeutics to
      control B cell responses in autoimmune disease and the design of effective
      vaccines to control infectious diseases.

PMID- 18810336
TI  - Regulation of G-protein-coupled signaling pathways in allergic inflammation.
AB  - Allergic diseases such as asthma are elicited by maladaptive activation of immune
      cells such as mast cells and lymphocytes by otherwise innocuous allergens. The
      numerous mediators secreted by such cells promote both acute inflammation and, in
      many instances, chronic tissue remodeling. Most of these compounds exert their
      effects on end-organ targets such as epithelial and endothelial cells and airway
      smooth muscle by activating G-protein-coupled receptors (GPCRs), which are by far
      the most abundant type of cell surface receptor. Since GPCRs are also the most
      common target of allergy therapeutics, a better understanding of their
      intracellular signaling mechanisms is vital to improve the efficacy of such drugs
      or to develop new targets. In this review, we focus on some of the new regulatory
      elements that control the duration and amplitude of GPCR signal transduction
      pathways in immune effector cells and end-organ structural cells affected by
      allergic inflammation.

PMID- 18810337
TI  - Supplemental food may not prevent iron-deficiency anemia in infants.
AB  - OBJECTIVE: The present study evaluates the role of supplementary food and
      medicinal iron intake in preventing iron deficiency anemia in children aged
      between 4 to 6 months. METHODS: During a case-control study in "Tabriz Children
      Hospital", nutritional and medicinal-iron intake of 60 consecutively selected
      patients with iron-deficiency anemia were compared with 60 non-anemic children of
      similar age and sex distributions. RESULTS: The mean hemoglobin concentration,
      corpuscular volume and serum iron were 9.11 g/dl, 65.41 fL and 19.33 microg/dl,
      in case group; and 12.6 g/dl, 75.18 fL and 78.28 microg/dl, in control group,
      respectively. There was no statistically significant difference between age of
      case and control groups when complementary-semisolid foods were started
      (P=0.058), but the mean of received medicinal iron in case group was
      significantly lower than control group (P<0.001). CONCLUSION: Supplementary food
      intake alone is not efficient to prevent iron deficiency anemia since the age of
      4-6 months. So, regular administration of medicinal iron is crucial to prevent
      iron-deficiency anemia in children aged 4-6 months.

PMID- 18810338
TI  - Vallecular cyst-revisited.
AB  - We report a 3 months-old-male infant presented with recurrent cough, noisy
      breathing and regurgitation of feeds since 15 days of life. Examination revealed
      inspiratory stridor. CECT showed cystic lesion in base of tongue. After excision
      it was proved a case of vallecular cyst on histopathology. Although rare,
      vallecular cyst should be included in the differential diagnosis of congenital
      laryngeal stridor in neonates. The literature of vallecular cyst is being
      reviewed in the current article.

PMID- 18810339
TI  - Rhombencephalosynapsis: association with single umbilical artery.
AB  - A 6-year-old girl who presented with developmental delay and non-progressive
      ataxia is described. MRI of brain showed agenesis of cerebellar vermis with
      fusion of cerebellar hemispheres and dentate nuclei. MRI findings were
      characteristic of rhombencephalosynapsis. Partial agenesis of corpus callosum and
      absent septum pellucidum were also seen. The child had also been noted to have a
      single umbilical artery at birth: a hitherto undescribed association.

PMID- 18810340
TI  - Off-label drug use in children.
AB  - OBJECTIVE: To determine the extent and nature of off-label drug use in children
      admitted to a pediatric general ward in a tertiary health care centre METHODS:
      Consecutive patients aged 1 mo-12 years admitted to the general wards in a
      tertiary care center in Mumbai over a two-month period were prospectively
      enrolled in the study. British National Formulary [BNF] version 2005 was used to
      ascertain if the drug use was "off-label". The off-label use was categorized as:
      administration of a greater/lesser dose, administration at a higher/lower
      frequency than indicated, administration for indications not described,
      administration of a drug not licensed for use in that age group and/ or use of
      alternative routes of administration. Descriptive statistics was used for
      calculating the off-label drug use. RESULTS: Two thousand prescriptions received
      by 600 subjects (M:F= 1.47:1) were analyzed. One thousand and forty-five (50.62%)
      prescriptions were off-label. The off-label drug use rate was 1.74+/-1.56 per
      patient. The maximum rate of off-label drugs was in infants (2.33/patient).
      'alteration in dosage' was by far the commonest reason for off-label use;
      followed by 'age' and 'indication'. Furosemide (i. v.), diazepam (i.v),
      cefotaxime (i.v), ethambutol (tab) and prednisolone (tab) were the five commonest
      off-label drugs used in the study population. CONCLUSIONS: Off-label drug use was
      highly prevalent in general pediatric ward of a tertiary care hospital in India.

PMID- 18810341
TI  - Primary hyperoxaluria type 1 with a novel mutation.
AB  - Primary hyperoxaluria type 1 [PH1] is an autosomal recessive disorder caused by a
      deficiency of alanine-glyoxylate aminotransferase AGT, which is encoded by the
      AGXT gene. We report an Indian family with two affected siblings having a novel
      mutation in the AGXT gene inherited from the parents. The index case progressed
      to end stage renal disease at 5 months of age. His 4 month old sibling is
      presently under follow up with preserved renal function.

PMID- 18810343
TI  - Effect of low cost public health staff training on exclusive breastfeeding.
AB  - OBJECTIVE: To assess the effectiveness and feasibility of on the job staff
      training and supportive supervision to improve six months Exclusive Breastfeeding
      (EBF). METHODS: A longitudinal study was conducted in a public health field
      practice area-Sri Lanka in 2006-2007. Three breastfeeding counseling sessions
      were conducted for public health midwives. Supportive supervision and on the job
      training were done by two public health physicians. Pre and post intervention
      independent cross sectional studies were conducted to assess the effectiveness of
      the programme. The study sample consisted of mother-infant pairs where infants
      were aging 6 to 12 months, attending child welfare clinics. Primary outcome
      measure was the proportion of infants who received EBF up to 6 months. Logistic
      regressing model was used for analysis of predictors of EBF. RESULTS: Study
      sample consisted of 336 mother-infant pairs (pre 139, post 197). Proportion of
      mothers who breastfed their infants exclusively for six months improved from 19%
      to 70% after the intervention. The median duration of EBF increased from 4 months
      to 6 months (inter-quartile range 2-6 and 5-6 months respectively). Unconfounded
      effect of intervention on 6 months EBF in logistic regression model was highly
      significant (OR=13.67. p<0.001). Intervention significantly reduced the bottle
      feeding rate (OR=0.212, p<0.001) but not formula feeding (OR=1.146. p=0.642). Of
      potential predictors assessed. Sinhalese mothers than Muslim mothers (OR=3.37,
      p<0.001) and employed mothers compared to housewives (OR=4.45. p=0.014) were more
      likely to breastfeed their infants upto six months. Parity, maternal education
      and maternal age were not significantly associated with six months EBF.
      CONCLUSIONS: The existing public health infrastructure can be used effectively to
      improve six months EBF in places where the care is given primarily by public
      health system.

PMID- 18810344
TI  - Perinatal outcome after multifetal pregnancy reduction.
AB  - OBJECTIVE: To assess multifetal pregnancy reduction in Indian context. METHODS:
      It is a retrospective descriptive study. Perinatal outcome of 92 multifetal
      pregnancies were retrieved from a well maintained database. Fetal reductions were
      carried out using standard protocol. RESULTS: There were 92 pregnancies referred
      for fetal reduction during the study period. Out of 92, twelve pregnancies
      (20.3%) had fetal or neonatal losses; of which complete pregnancy loss rate was
      8.5% and partial pregnancy loss rate was 11.8%. Twenty one (35.6%) pregnancies
      had premature deliveries. The median birth weight was 2100 grams. Four babies
      were born alive with congenital anomalies. CONCLUSION: Our study showed the
      median birth weight, rates of pregnancy loss and prematurity after the fetal
      reduction procedure was comparable with other studies. However, it must be noted
      that the rate of loss to follow up was higher in our study.

PMID- 18810345
TI  - Tectocerebellar dysraphia and occipital encephalocele: an unusual association
      with abdominal situs inversus and congenital heart disease.
AB  - Tectocerebellar dysraphia is a rare constellation of malformations comprising of
      occipital encephalocele, aplasia of the cerebellar vermis and deformity of the
      tectum. We describe a 7 month old infant who presented with tectocerebellar
      dysraphia associated with double outlet right ventricle, pulmonary stenosis and
      abdominal situs inversus. This association has not been reported in the
      literature, to the best of our knowledge.

PMID- 18810346
TI  - Amebic cerebral abscess mimicking bacterial meningitis.
AB  - We report a case of an amebic brain abscess in a 2-year-old girl, with symptoms
      mimicking bacterial meningitis with no evidence of disease elsewhere.
      Histological evaluation of the abscess revealed the organisms, and the abscess
      regressed in response to specific medical treatment. This article reviews the
      rarity of these abscesses and difficulty in the diagnosis.

PMID- 18810347
TI  - Wandering spleen presenting as recurrent abdominal pain in a young female.
AB  - A young female child presented to our OPD for evaluation of recurrent abdominal
      pain. During the process of investigation USG abdomen and subsequently CECT
      abdomen revealed pelvic location of spleen. Splenopexy was performed and patient
      discharged. Patient is asymptomatic and on regular follow up.

PMID- 18810348
TI  - Tularemia in children.
AB  - OBJECTIVE: Tularemia, an infection caused by the coccobacilus Francisella
      tularensis, can be a difficult disease process to diagnose and treat. The aim of
      this study was to evaluate an epidemic of tularemia in Bursa. METHODS: In this
      study, we included only pediatric cases. All the cases were diagnosed on clinical
      and serological grounds. RESULTS: During an epidemic of tularemia in a village of
      Bursa on December 2004, 70 people (60 adults, 10 children) fell ill. In children
      with tularemia, the oropharyngeal form predominated which was diagnosed 70% of
      cases. Most of the patients (80%) who had older than 10 years old, were treated
      with doxycycline. All patients recovered without complications. CONCLUSION: The
      epidemic was thought to be waterborne. The vehicle of the infections was
      inadequately treated water which was used by the patient in the village.

PMID- 18810349
TI  - Iniencephaly: association with unusual congenital malformations.

PMID- 18810350
TI  - Antinuclear antibodies in Mycobacterium tuberculosis infection.

PMID- 18810351
TI  - Necrotizing adenoviral pneumonia: manifestation of nosocomial infection in
      pediatric intensive care unit.
AB  - A 5-year-old child admitted in the pediatric intensive care unit developed fever
      and crepitations in the chest on 6(th) day of admission. She succumbed to her
      illness depite administration of adequate supportive and ventilatory care and
      anti-microbial therapy. At autopsy, she was diagnosed to have chronic ligneous
      type of tuberculous meningitis and necrotizing adnoviral pneumonia. There are
      hardly any reports of nosocomial adenoviral pneumonia from Indian centers. The
      case serves to remind intensivists to consider this diagnosis so that appropriate
      therapeutic adjustments and measures to prevent the spread of infection to other
      critically ill subjects are initiated.

PMID- 18810352
TI  - VP16CREB-induced differentiation of neuroblastoma.
AB  - OBJECTIVE: Drug-induced differentiation is commonly used as a therapeutic
      modality for the treatment of neuroblastoma tumors. Increased level of cyclic
      adenosine 3', 5'-monophosphate (cAMP) mediates terminal differentiation in some
      neuroblastoma cell lines through activation of several signaling networks,
      including cAMP response element binding protein (CREB). Objective was to test
      whether cAMP-induced differentiation in a murine neuroblastoma cell line (NBP2)
      is partly mediated by CREB. METHODS: Fluorescent microscopy was used to document
      neuron-like morphological changes imparted by a constitutively active CREB
      (VP16CREB). Real time PCR (RT-PCR) was performed to verify changes in the
      expression of cAMP/CREB responsive genes. RESULTS: It was found that transient
      expression of VP16CREB into NBP2 cells resulted in morphological changes that
      were characteristics of terminally differentiated neurons. Furthermore, increased
      expression of cAMP responsive genes was compromised in cells resisting VP16CREB
      mediated differentiation. CONCLUSION: A constitutively active CREB induces
      terminal differentiation in a subset of NBP2 cell population. Altered expression
      of cAMP responsive genes may account for differentiation resistant phenotype in
      NBP2 cells.

PMID- 18810353
TI  - Dengue, HIV and thrombocytopenia.

PMID- 18810354
TI  - Vascular endothelial growth factor levels in newborns with meconium stained
      amniotic fluid.
AB  - OBJECTIVE: The effects of meconium-stained amniotic fluid (MSAF) on cord blood
      vascular endothelial growth factor (VEGF) levels have not been explored. The aim
      of this study was to verify whether MSAF influences cord blood VEGF levels in
      healthy term neonates and we can use cord blood VEGF levels in infants with MSAF
      as an indicator of fetal distress. METHODS: Using an enzyme-linked immunosorbent
      assay double sandwich method, plasma VEGF levels were determined in 18 healthy
      term neonates with MSAF and in 16 healthy term neonates without MSAF. RESULTS:
      VEGF plasma levels were not significantly different between healthy term neonates
      with or without MSAF. CONCLUSION: Intrauterine meconium passage could not affect
      VEGF levels on cord blood in term newborn infants and VEGF level may not be used
      as an indicator of fetal distress in infants with MSAF.

PMID- 18810355
TI  - Evaluation of chronic abdominal pain--a test of "patience".
AB  - A 4 year old girl with chronic abdominal pain of 6 months duration was
      provisionally diagnosed as eosinophilic gastroenteritis based on endoscopic
      biopsy This case is reported for its rarity.

PMID- 18810356
TI  - Can necrotizing fasciitis be the first symptom of Hyperimmunoglobulin E syndrome.

PMID- 18810357
TI  - Reactive hemophagocytic syndrome.
AB  - We describe two cases of Reactive Hemophagocytic syndrome (RHS) occurring in
      rheumatic diseases in childhood. Patient 1, an adolescent girl with systemic
      onset Juvenile idopathic arthritis (JRA) presented like severe sepsis with shock,
      hepatic dysfunction and coagulopathy. Patient 2 presented with cardiac tamponade,
      she was later detected to have systemic lupus erythematosus (SLE). Her bone
      marrow aspirate revealed prominent hemophagocytosis. Both cases improved with
      pulse methylprednisolone therapy.

PMID- 18810358
TI  - Dermal sinus tract: an OFT overlooked cause of E. coli meningitis.

PMID- 18810359
TI  - The posterior reversible encephalopathy syndrome.
AB  - The posterior/potentially reversible encephalopathy syndrome is a unique syndrome
      encountered commonly in hypertensive encephalopathy. A 13-year-old boy presented
      with of intermittent high grade fever, throbbing headache and non-projective
      vomiting for 5 days. The patient had a blood pressure of 120/80 mmHg but
      fundoscopy documented grade 3 hypertensive retinopathy. The patient improved
      symptomatically following conservative management. However, on the 5(th) post
      admission day headache reappeared, and blood pressure measured at that time was
      240/120 mmHg. Neuroimaging suggested white matter abnormalities. Search for the
      etiology of secondary hypertension led to the diagnosis of pheochromocytoma.
      Repeated MRI after successful surgical excision of the tumor patient showed
      reversal of white matter abnormalities. Reversible leucoencephalopathy due to
      pheochromocytoma have not been documented in literature previously.

PMID- 18810360
TI  - Prevalence of underweight and stunting among school children in West Bengal.

PMID- 18810361
TI  - Opium as a fatal substance.
AB  - OBJECTIVE: Poisoning does the most serious damages in pediatrics. In the
      northeast of Iran (Golestan province), opium is used widely for symptomatic
      therapy of routine illnesses in young children by parents. In the present study,
      opium toxicity was assessed in young children referred to pediatric centers in
      our area. METHODS: This survey was done as a prospective cross-sectional study.
      At first, a pilot study was undertaken to estimate the condition of opium
      intoxicated children and evaluate the validity of questionnaire. We collected
      data in collaboration with committee of Adverse Drug Reactions (ADR) in Golestan
      Province. All members of ADR committee in pediatric centers were trained to
      complete questionnaires in referred or admitted children under-5-year. Data was
      entered into computer and analyzed by Chi-square and Fisher exact test. RESULTS:
      In this survey, 67 opium-intoxicated children were recruited. Minimum age of the
      cases was 6 days and maximum 5-year. Uneducated mothers, in most cases, gave
      opium to the child. Most of them were from the low socio-economic level. Ethnic
      was disparity was observed. Four deaths occurred. CONCLUSION: As the results
      showed, opioids are dangerous in pediatric population, especially under 5-year.
      Respiratory depression, bradypnea, coma and death are the serious outcomes of
      opium toxicity in pediatrics. Such a practice of unrestricted use of opium
      contributes to children mortality and so it is essential to launch educational
      programs.

PMID- 18810362
TI  - Diagnosis and treatment of pulmonary cystic hydatidosis.
AB  - OBJECTIVE: Hydatidosis is a parasitic infection that is still an important public
      health problem in Turkey. In the present study, it was planned to review the
      diagnostic and treatment options. METHODS: The study was conducted in pediatric
      pulmonary chest ward of Izmir Chest Diseases and Surgery Training Hospital, a
      referral tertiary hospital for pulmonary diseases in Western Turkey. Cases were
      evaluated in clinical presentations, radiological, histopathologic and
      serological features retrospectively. RESULTS: Consecutive 17 (11 male and 6
      female; mean age 11.29 + 2.44) pediatric cases between 1996 and 2001 were
      evaluated. Liver involvement was found in 8 (47%) cases. Casoni skin test and IHA
      test were found positive in 7 (63.6%) and 8 (72.7%) out of 11 cases,
      respectively. Surgical treatment was performed only in 7 (41.1%) cases as well as
      surgical plus medical treatment was given in 3 (17.6%) cases. Seven (41.1%) cases
      were treated just medically. CONCLUSION: Hydatidosis should be considered in the
      existence of appropriate clinical and radiological findings as a probable
      diagnosis in all children in our region. Surgery should be the first choice for
      treatment but, medical therapy was considered as effective for treatment
      complicated and/or nonsurgical pediatric cases.

PMID- 18810363
TI  - Child survival and the need for wider dissemination of health research.
AB  - The Bellagio meeting on child survival was held in February 2003, where first
      reliable estimates on child morbidity and mortality were made and, the effective
      preventive and treatment interventions for reducing under five child deaths were
      identified. The meeting gave a momentum to child survival efforts across the
      world. This review summarizes the child survival series published thereafter and
      outlines the evidences generated. The author argues that the meeting was a
      landmark step, and the need for these interventions is still the same as it was
      five years back. The author adds that health research has ever since been on the
      agenda of international community; however, the equally important step of wider
      dissemination of available knowledge, to fill the "delivery gap", has almost been
      neglected. This paper provides evidences of how health research and its wider
      access to policy makers and implementers can improve the child survival. The
      author also calls for an immediate mechanism to make health research easily
      available and accessible, to the practitioners in the developing nations.

PMID- 18810364
TI  - Re: Effect of pregnancy induced hypertension on mother and babies.

PMID- 18810365
TI  - Gene polymorphisms of IL-6(-174) G/C and IL-1Ra VNTR in asthmatic children.
AB  - OBJECTIVE: To check for the association of genetic polymorphisms of IL-6-(
      174)G/C and IL-1RaVNTR with the susceptibility and severity of asthma in Egyptian
      children. METHODS: Subjects included 69 asthmatic children and 98 healthy
      unrelated controls from the Nile Delta of Egypt. Cases consisted of 20 males and
      49 females with an age mean +/- SD is 7.5 +/- 2.1 ranging between 2-13 years. DNA
      amplification using PCR with sequence-specific primers was done for detection of
      promotor single nucleotide polymorphism of IL-6 gene as well as intron 2 VNTR of
      IL-1Ra gene. Frequency of case-genotypes or alleles were compared to controls
      using Fisher exact test and Odds ratio. RESULTS: Cases showed significant higher
      frequency of the genotypes: IL-6-174 GG (P<0.05, OR=3.2, 95% CI=1.09-10) that was
      evident mainly in the uncontrolled asthma subgroup indicative of the possibility
      of being a severity genotype. All cases as well as case-subgroups showed high
      significant frequency of IL-1Ra A1A1 (p<0.0001, OR=1.5, 95% CI=1.3-1.8). This may
      be considered a susceptibility genotype. Cases have also shown significant lower
      frequency of IL-6(-174) GC and IL-1Ra A1A2 genotypes (P<0.001 and P<0.0001
      respectively). CONCLUSION: IL-6 and IL-1Ra polymorphisms can be considered
      genetic markers for bronchial asthma susceptibility and/or severity among
      Egyptian children. This may have a potential impact on family counseling and
      management.

PMID- 18810366
TI  - Impact of an educational program on parental knowledge of cerebral palsy.
AB  - OBJECTIVES: To investigate parental knowledge of cerebral palsy, and to evaluate
      the impact of an educational intervention on it. METHODS: From May 2003 to April
      2004, 26 parents of newly diagnosed children with cerebral palsy were
      interviewed. After the interview, each parent was administered a structured
      educational program and re-interviewed after three months. The pre and post
      intervention responses were compared using Chi-square test. RESULTS: After the
      intervention, there was a significant improvement in parental knowledge: (i) of
      the cause of the disorder (5/26 vs 20/26, P = 0.0001), (ii) that it is non
      progressive (16/26 vs 24/26, P = 0.021), (iii) that it is not curable (10/26 vs
      23/26, P = 0.0005), (iv) that it is treatable (12/26 vs 24/26, P=0.0009), (v) of
      the frequency and duration of therapy necessary to improve functional abilities
      (7/26 vs 17/26, P = 0.005), and, (vi) of the importance of following up regularly
      with a pediatrician (17/26 vs 26/26, P = 0.003). However, there was no
      significant improvement in parental knowledge: (i) of the meaning of the term
      'cerebral palsy' (0/26 vs 5/26, P = 0.060), (ii) that 'early intervention
      therapy' given by a team of therapists is its recommended therapy (18/26 v 23/26,
      P = 0.174), (iii) of the meaning of the term 'early intervention therapy' (12/26
      vs 17/26, P = 0.163), and (iv) that it is preventable with good medical care
      (8/26 vs 10/26, P = 0.560). CONCLUSION: Parental knowledge of cerebral palsy is
      inadequate. A single-session educational program can significantly improve
      parental knowledge about many 'core basic issues' regarding cerebral palsy.

PMID- 18810368
TI  - [Teaching emergency medicine at the University Medical Center Freiburg:
      establishment of an integrative concept].
AB  - Efforts to improve the quality of undergraduate medical education are commonly
      hampered by limited human and financial resources. This deficiency may be offset
      by the development of well structured and innovative teaching concepts, which
      optimize available assets. The newly conceived modular course "Emergency
      Medicine" at the University Medical Center Freiburg was conducted for the first
      time in the winter semester 2006/2007. The core of the course is a 3-day
      practical training period. It provides the possibility to teach a maximum number
      of medical students with only four lecturers using patient simulators,
      interactive case scenarios (simulation software MicroSim), and case scenarios
      with standardized patients. Evaluation of the course revealed standardized
      patients to be the best of all teaching methods with an overall average grade of
      1.1 (patient simulators 1.2, computer simulation 1.4). Of the students, 88%
      stated that the practical training encouraged their interest in the speciality
      emergency medicine. The excellent student evaluation results show that the new
      course "Emergency Medicine" for medical students constitutes a successful balance
      between the constraint of resource limitation and the goal of excellent medical
      education.

PMID- 18810367
TI  - [Expedition glycocalyx. A newly discovered "Great Barrier Reef"].
AB  - Healthy vascular endothelium is luminally coated by an endothelial glycocalyx,
      which interacts with the bloodstream and assumes a filter function on the
      vascular wall. Although this structure was discovered nearly 70 years ago, its
      physiological importance has been underestimated for a long time. Recent findings
      indicate that the glycocalyx is, in addition to the endothelial cells themselves,
      a main constituent part of the vascular barrier. The existence of different
      colloid osmotic gradients within and beneath this structure has now led to a
      modification of the Starling equation. In many vascular beds the interstitial
      space features a protein concentration similar to that of the plasma. The
      inwardly directed gradient, which retains water and proteins in the vascular
      system, is generated beneath the glycocalyx by selective protein filtration over
      this structure. The endothelial glycocalyx, as an additional competent vascular
      permeability barrier has, therefore, not only a key role for perioperative fluid
      and protein shifts into the interstitial space, but it seems to be intimately
      involved in the pathophysiology of diabetes, arteriosclerosis, sepsis and
      ischemia/reperfusion, especially with respect to associated vascular
      dysfunctions. The fragile glycocalyx can be destroyed in the course of surgery,
      trauma, ischemia/reperfusion and sepsis and by inflammatory mediators such as TNF
      alpha, causing leukocyte adhesion, platelet aggregation and edema formation.
      Recent studies have shown that protecting this structure not only maintains the
      vascular barrier, but constitutes an important component of a rational
      perioperative fluid therapy.

PMID- 18810369
TI  - [Esophageal necrosis following endovascular treatment of a ruptured thoracal
      aortic aneurism: caused by mediastinal compartment syndrome].
AB  - We report a case of acute esophageal necrosis after endovascular stenting for
      acute rupture of a thoracic aortic aneurysm into the mediastinum caused by
      mediastinal compartment syndrome and overstenting of intercostal arteries.

PMID- 18810370
TI  - [Kyphoplasty : method for minimally invasive treatment of painful vertebral
      fractures].
AB  - Painful osteoporotic and malignant vertebral fractures are frequent causes of
      chronic back pain with negative consequences regarding immobility, quality of
      life, morbidity, mortality, and fracture incidence. The best currently available
      evidence-based treatment reduces vertebral fracture risk but does not totally
      prevent follow-up fractures. Kyphoplasty is a causal treatment of pain by
      internal stabilization that prevents the ongoing pain of constant vertebral
      (micro-)fracture. The indication for this minimally invasive procedure requires
      interdisciplinary discussion of the individual case to guarantee technical
      feasibility, increase the likelihood that kyphoplasty will indeed reduce pain,
      and embed this procedure in the individual patient's long-term therapeutic
      concept or treatment of painful vertebral metastases. In addition to internal
      stabilization of painful vertebral fractures, kyphoplasty seeks to restore lost
      vertebral height, which appears promising in acute and painful vertebral
      fractures. Available controlled prospective studies demonstrate long-term patient
      benefits in terms of pain reduction, mobility, and improved quality of life.

PMID- 18810371
TI  - [Knowledge about UV-radiation and sun protection: survey of adolescents and young
      adults in Bavaria].
AB  - BACKGROUND: Identifying deficits in sun protection knowledge and behavior can
      serve as a starting point for primary prevention interventions. The aim of this
      study was to investigate knowledge and behavior related to ultraviolet radiation
      in the population between 14 and 45 years of age in Bavaria, as well as effects
      of the awareness campaign "Sensible in the Sun". METHODS: In two Bavarian
      districts, 545 individuals of the target population completed a telephone survey
      about risks of UV-radiation, sun protection knowledge and behavior, and effects
      of the campaign. RESULTS: Sunburn and skin cancer as adverse effects of
      ultraviolet radiation were named by almost every participant. When asked about
      protective interventions, 91% mentioned sunscreen and 45-54% clothing, limited
      stay in the sun and seeking shade at noon. Women were better informed than men,
      adults better than adolescents. 10.6% were aware of the campaign. In this group,
      37.9% had been motivated to consider their sun protective behavior; 13.8%
      (especially women >30 years) stated they had changed their behavior because of
      the campaign. CONCLUSION: There were deficits in knowledge, especially about eye
      damage and the importance of getting slowly used to UV radiation. Physician
      advice, but also broadcast and print media, has an effect on UV-related
      knowledge.

PMID- 18810372
TI  - [Surgical treatment of vestibular vertigo: methods and indications].
AB  - After the failure of medical treatment of dizziness or vertigo, surgical
      treatment is chosen according to functional diagnosis and duration and severity
      of symptoms. Surgery is contraindicated in patients with incomplete vestibular
      compensation, central nervous disorders and bilateral vestibular deficits.
      Surgery is obligatory in cases of sudden loss of labyrinthine function with
      traumatic perilymph fistula, middle ear and temporal bone processes.
      Endolymphatic hydrops and pathological endolymph pressure of other etiology as
      impaired middle ear ventilation, EVAS or superior semicircular canal dehiscence
      can be treated surgically. Resurfacing of dehiscence with glas ceramic implants
      is presented. Occlusion of the posterior semicircular canal is restricted to
      extremely rare conditions with non-responders to repositioning maneuvers.
      Ablative procedures, such as cochleosacculotomy and vestibular neurectomy are
      rarely indicated. More than 85% of non-responders to conservative treatment
      procedures in vestibular dysfunction can be improved by means of surgical
      procedures. Otologists have access to procedures for differentiation, indications
      and therapy via the network of general practitioners and hospital physicians.

PMID- 18810373
TI  - [Function disorders of otoliths: clinical aspects and therapy options].
AB  - In the clinical routine, the diagnostic of the lateral gait is often comparable
      with a complete peripheral vestibular function examination. Diseases of the
      otolithic organs, with the saccule and utricle are not identified with
      conventional clinical examination methods. In more than 50% of patients with
      thermal hypostimulation, orientation tests show a simultaneous pathology of the
      utricle function. Participation of the saccule has been described for vestibular
      neuropathy, Meniere's disease, bilateral vestibulopathy and acoustic neurinoma.
      Both otolithic organs are included in posttraumatic vertigo, a recognition, which
      will influence expert opinions in the future. Only by an exact diagnostic of
      diseases of the otolithic organs can individual disease courses be differential
      diagnostically separated from each other.

PMID- 18810375
TI  - [Pathophysiology of bone metabolism].
AB  - Osteoporosis is a multifactorial disease entailing a high risk to sustain
      fragility fractures. Its susceptibility is determined by genetic and
      environmental factors and underlying diseases. Bone is rebuilt and regenerated by
      osteoclasts, osteoblasts and osteocytes. Local and systemic growth and
      differentiation factors such as Insulin-like growth factors, bone morphogenetic
      proteins and wnt-proteins confer anabolic signals, while the RANK/RANK-Ligand and
      Osteoprotegerin (OPG) system regulates bone resorption. The ratio of osteoclast
      stimulating RANKL and its soluble decoy receptor OPG is modulated by sex
      hormones, vitamin D, parathyroid hormone, local growth factors and mechanical
      loading. Osteocytes regulate bone mass via the bone formation inhibitor
      sclerostin. Bone is tightly interconnected with and regulated by the
      calcium/phosphate/vitamin D system via the parathyroid gland, the gut, liver and
      kidneys. Sex hormones are important for bone formation during adolescence and
      their loss in menopause/andropause exaggerates bone resorption. Basically over
      activity of osteoclasts and/or functional deficits of osteoblasts can cause
      negative bone balance and favor osteoporosis.

PMID- 18810376
TI  - MicroRNA-128 inhibits glioma cells proliferation by targeting transcription
      factor E2F3a.
AB  - MicroRNAs are approximately 21nt single-stranded RNAs and function as regulators
      of gene expression. Previous studies have shown that microRNAs play crucial roles
      in tumorigenesis by targeting the mRNAs of oncogenes or tumor suppressors. Here
      we show that brain-enriched miR-128 is down-regulated in glioma tissues and cell
      lines when compared to normal brain tissues. Overexpression of miR-128 in glioma
      cells inhibited cell proliferation. A bioinformatics search revealed a conserved
      target site within the 3'untranslated region (UTR) of E2F3a, a transcription
      factor that regulates cell cycle progression. The protein levels of E2F3a in
      gliomas and normal brain tissues were negatively correlated to the expression
      levels of miR-128 in these tissues. Overexpression of miR-128 suppressed a
      luciferase-reporter containing the E2F3a-3'UTR and reduced the level of E2F3a
      protein in T98G cells. Moreover, knocking down of E2F3a had similar effect as
      overexpression of miR-128, and overexpression of E2F3a can partly rescue the
      proliferation inhibition caused by miR-128. Taken together, our study
      demonstrates that miR-128 can inhibit proliferation of glioma cells through one
      of its targets, E2F3a.

PMID- 18810377
TI  - Mononuclear inflammatory cells and angiogenesis.

PMID- 18810378
TI  - Chromosomal changes characterize head and neck cancer with poor prognosis.
AB  - It is well established that genetic alterations may be associated to prognosis in
      tumor patients. This study investigates chromosomal changes that predict the
      clinical outcome of head and neck squamous cell carcinoma (HNSCC) and correlate
      to characteristic clinicopathological parameters. We applied comparative genomic
      hybridization (CGH) to tissue samples from 117 HNSCC patients scheduled for
      radiotherapy. Genomic aberrations occurring in more than five patients were
      studied for impact on locoregional progression (LRP)-free survival. p values were
      adjusted by the Hochberg-Benjamini procedure and significant aberrations and
      clinical variables subjected to a stepwise backwards Cox proportional model.
      Significant alterations were further analyzed by array-CGH and fluorescence in
      situ hybridization (FISH). In multivariate survival analysis gains on 1q and 16q
      predict reduced LRP-free survival independently from known prognostic factors.
      Cluster analysis separated the HNSCC cases into two groups (cluster 1 and 2) that
      are characterized by significant differences for imbalances in 13 chromosomal
      regions. Moreover, it became apparent that cluster 1 correlates to nonanemic
      patients, while cluster 2 represents predominantly anemic cases. Array-CGH
      pinpoints 16q24.3 to be the region of interest on chromosome 16 which was further
      verified by FISH analysis where an increased copy number of FANCA, a member of
      the Fanconi anemia/breast cancer pathway, could be identified. This study
      demonstrates that chromosomal gains on 1q and 16q as well as chromosomal loss on
      18q represent prognostic markers in HNSCC and that these alterations may explain
      to some extent the dismal course of a subgroup of patients.

PMID- 18810379
TI  - [Significance of sonography in traumatology and orthopedics: part 1:
      ultrasonography of the musculoskeletal system].
AB  - A wide variety of modern ultrasound systems - including linear probes (7.5-15
      MHz) and curved array probes (3.5-7.5 MHz), with color Doppler and duplex as well
      as harmonic imaging are used in trauma surgery and orthopedics to image and
      investigate almost all regions of the body. It is generally possible to assess
      all joints by ultrasonography. Valid procedures for ultrasonographic examination
      of the elbow, hip, knee, and ankle joints have been described in the literature.
      In the clinical setting, the use of ultrasound to examine the Achilles tendon and
      joints such as the shoulder and knee is particularly well documented. An
      important feature of ultrasound is that it allows dynamic examinations and side
      to-side comparisons. Because ultrasonography is a very widely used imaging
      modality, it is a useful tool for screening and monitoring and especially for
      investigating venous thrombosis and diseases and injuries of the tendons and
      muscles.

PMID- 18810380
TI  - [Alzheimer's disease and vascular dementia. Determination of atrophy of the
      corpus callosum and cerebral cortex].
AB  - BACKGROUND: Measurement of regional atrophy of the corpus callosum and cortical
      grey matter may differentiate between primary loss of intracortical projecting
      neurons and primary fibre degeneration in Alzheimer's disease (AD) and vascular
      dementia (VD). METHODS: The regional corpus callosum area and cortical grey
      matter volumes were measured in 30 patients with the clinical diagnosis of
      probable AD, 20 patients with the clinical diagnosis of probable VD and 24
      healthy elderly control subjects using MRI in two centers in Munich and
      Amsterdam. RESULTS: Patients with AD showed significantly reduced volumes of
      cortical grey matter in all cerebral lobes and atrophy of anterior and posterior
      corpus callosum areas. In VD patients only occipital lobe grey matter volume and
      anterior corpus callosum area were significantly reduced. In AD patients
      reduction of cortical grey matter volumes was significantly correlated with
      regional reductions of corpus callosum areas, but not in VD patients or controls.
      CONCLUSION: These findings support the notion that measurement of the corpus
      callosum and cortical grey matter atrophy may identify the underlying causes of
      cortical disconnection in AD and VD and may be helpful to differentiate between
      both conditions.

PMID- 18810381
TI  - [Treatment strategies for local advanced prostate cancer].

PMID- 18810382
TI  - [Value of cystoprostatectomy in locally advanced prostate carcinoma].
AB  - Patients suffering from locally advanced prostate carcinoma are often stressed by
      debilitating local symptoms limiting their quality of life. At the same time life
      expectancy often exceeds several years, whereas urologists and oncologists tend
      to underestimate their patients' life expectancy. Cystoprostatectomy for locally
      advanced prostate carcinoma is a reasonable therapeutic option concerning
      frequency and kind of imminent complications and possibly alleviates or
      completely eliminates local symptoms in 80% or more. According to the literature
      cancer-specific 10-year survival rates are 38% or median cancer-specific survival
      lies between 24 and 31 months. The role of neoadjuvant or adjuvant hormonal
      therapy, chemotherapy, or radiotherapy has not yet been defined. Mostly after
      cystoprostatectomy due to locally advanced prostate carcinoma an ileal conduit is
      formed for urinary diversion, but also orthotopic neobladders or continent
      pouches are used. Incontinence rates for orthotopic neobladders may reach 50% and
      more. In synopsis cystoprostatectomy may be a viable therapeutic option for
      patients suffering from locally advanced prostate carcinoma. It surely is
      important that the indication for surgery is based on an individual decision.

PMID- 18810383
TI  - [pT3R1 prostate cancer : Immediate or delayed radiotherapy after radical
      prostatectomy?].
AB  - Approximately 50-60% of patients with tumor stage pT3R1 after radical
      prostatectomy (RP) who do not receive adjuvant therapy develop biochemical
      progression. At present it is unclear whether these patients should undergo
      immediate adjuvant irradiation or whether a wait and see approach should be
      adopted while monitoring PSA until the PSA level rises from zero and then
      initiate salvage radiotherapy (SRT).Three randomized trials showed that an
      absolute improvement of 20% in the 5-year biochemical no evidence of disease
      (bNED) could be achieved by administering adjuvant radiotherapy with 60 Gy in
      patients with tumor stage pT3R1, even with a PSA level around zero after RP. The
      rate of serious late effects is low. On the other hand, there are numerous,
      albeit retrospective studies, which provide evidence that SRT after an increase
      in PSA above zero is an effective treatment, but with higher total doses of 66-70
      Gy and a higher rate of late effects. Prognostic factors such as the PSA level
      before radiotherapy is started, PSA doubling time, R1 resection, PSA velocity,
      and the Gleason score have a significant impact on both the return of the PSA
      level to zero and the bNED. Depending on the risk factor, between 20 and 70% of
      patients again achieve PSA levels around zero after SRT. Retrospective
      comparative studies suggest a benefit of adjuvant radiotherapy; prospective
      randomized trials do not exist.Adjuvant radiotherapy after RP in stage pT3R1
      tumor and SRT in cases of PSA rising above zero or persistent PSA levels are
      valid options for the management of high-risk patients after RP. SRT requires
      higher total doses and thus carries a higher risk of late complications. A
      benefit has been demonstrated for bNED, but not for survival. The approach should
      be discussed with the individual patient.

PMID- 18810384
TI  - Molecular mapping of two reverse photoperiod-sensitive genic male sterility genes
      (rpms1 and rpms2) in rice (Oryza sativa L.).
AB  - The reverse photoperiod-sensitive genic male sterility (PGMS) and thermo
      sensitive genic male sterility (TGMS) lines have an opposite phenotype compared
      with normal PGMS and TGMS lines widely used by the two-line system in current
      hybrid rice seed production. Thus, the application of reverse PGMS and TGMS lines
      can compensate PGMS and TGMS lines in hybrid rice production. YiD1S is a reverse
      PGMS line, in which pollen fertility is mainly regulated by day-length, but also
      influenced by temperature. Genetic analysis indicated that male sterility of
      YiD1S was controlled by two recessive major genes. An F(2) population from a
      cross between YiD1S and 8528 was developed and used for molecular mapping of the
      two reverse PGMS genes which were first named rpms1 and rpms2. Both simple
      sequence repeat (SSR) markers and bulked segregant analysis (BSA) were used in
      this study. As a result, one reverse PGMS gene (rpms1) was mapped to the interval
      between SSR markers RM22980 (0.9 cM) and RM23017 (1.8 cM) on chromosome 8. Eight
      SSR markers, YDS818, RM22984, RM22986, RM22997, YDS816, RM23002, RM339 and YDS810
      completely co-segregated with the rpms1 gene. Another reverse PGMS gene (rpms2)
      was mapped to the interval between SSR markers RM23898 (0.9 cM) and YDS926 (0.9
      cM) on chromosome 9. The physical mapping information from publicly available
      resources shows that the rpms1 and rpms2 loci are located in a region of 998 and
      68 kb, respectively. The analysis based on marker genotypes showed that the
      effect of rpms1 was slightly larger than that of rpms2 and that the two genes
      interacted in controlling male sterility.

PMID- 18810385
TI  - Lifetime risk and projected population prevalence of diabetes.
AB  - AIMS/HYPOTHESIS: With incidence rates for diabetes increasing rapidly worldwide,
      estimates of the magnitude of the impact on population health are required. We
      aimed to estimate the lifetime risk of diabetes, the number of years lived free
      of, and the number of years lived with diabetes for the Australian adult
      population from the year 2000, and to project prevalence of diabetes to the year
      2025. METHODS: Multi-state life-tables were constructed to simulate the progress
      of a cohort of 25-year-old Australians. National mortality rates were combined
      with incidence rates of diabetes and the RR of mortality in people with diabetes
      derived from the Australian Diabetes, Obesity and Lifestyle study (a national,
      population-based study of 11,247 adults aged >or=25 years). RESULTS: If the rates
      of mortality and diabetes incidence observed over the period 2000-2005 continue,
      38.0% (95% uncertainty interval 36.6-38.9) of 25-year-olds would be expected to
      develop diabetes at some time throughout their life. On average, a 25-year-old
      Australian will live a further 56 years, 48 of these free of diabetes. On
      average, a 45-year-old person with diabetes can expect to live 6 years less than
      a person free of diabetes. The prevalence of diabetes is projected to rise from
      7.6% in 2000 to 11.4% by 2025. CONCLUSIONS/INTERPRETATION: If we maintain current
      diabetes incidence rates, more than a third of individuals will develop diabetes
      within their lifetime and in Australia there will an additional 1 million cases
      of diabetes by the year 2025.

PMID- 18810386
TI  - [Minimally invasive vs. transgluteal total hip replacement. A 3-month follow-up
      of a prospective randomized clinical study].
AB  - BACKGROUND: The aim of this prospective randomized study was to compare the
      results after total hip replacement (THR) using an MIS approach versus a regular
      transgluteal approach (Bauer approach). METHOD: We compared 20 THRs using a
      modified Watson-Jones minimally invasive approach (MIS group) with 20
      conventionally performed THRs using a Bauer approach (control group). In all
      cases, the same implants (Trilogy cup, MAYO stem) were used. The Harris Hip Score
      (HHS), the visual analogue scale, myoglobin level, and creatinine kinase level
      were measured preoperatively and up to 3 months postoperatively. RESULTS:
      Advantages of the MIS group were evaluated using the HHS in the categories of
      activity and range of motion 6 weeks postoperatively. In terms of function, gait,
      and total HHS, we found benefits in the MIS group 6 and 12 weeks postoperatively.
      Up to 48 h postoperatively, patients in the MIS group had lower myoglobin blood
      levels. No differences were found in creatinine kinase levels, pain sensation as
      measured by visual analogue scale, or implant positioning. CONCLUSION: Use of the
      minimally invasive Watson-Jones approach shows advantages compared with the
      transgluteal Bauer approach 6 and 12 weeks postoperatively. Up to now there has
      been no prospective randomized clinical study that has definitely shown the
      superiority of the minimally invasive procedure. For that reason, the
      conventional approaches in THR are still the gold standard.

PMID- 18810387
TI  - Regional and overall ventilation inhomogeneities in preterm and term-born
      infants.
AB  - OBJECTIVES: We compared ventilation inhomogeneity assessed by electrical
      impedance tomography (EIT) and multiple breath washout (MBW) in preterm and term
      born infants. We hypothesised that EIT measurements in spontaneously breathing
      infants are repeatable and that differences in regional ventilation distribution
      measured by EIT can distinguish between preterm and term-born infants. DESIGN:
      Cross-sectional group comparison study. SETTING: Lung function laboratory at a
      University Children's Hospital. PARTICIPANTS: Seventeen healthy term-born and 15
      preterm infants at a matched postmenstrual age of 44 weeks. MEASUREMENTS AND
      RESULTS: We concurrently measured ventilation inhomogeneity by EIT, ventilation
      inhomogeneity (LCI) and functional residual capacity (FRC) by MBW and tidal
      breathing variables during unsedated quiet sleep. EIT measurements were highly
      repeatable (coefficient of variation 3.6%). Preterm infants showed significantly
      more ventilation of the independent parts of the lungs compared to healthy term
      born infants assessed by EIT (mean difference 5.0, 95 CI 1.3-8%). Whereas the two
      groups showed no differences in lung volumes or ventilation inhomogeneities
      assessed by MBW, EIT discriminated better between term and preterm infants.
      (FRC/kg: mean difference 1.1 mL, 95% CI -1.4-3.8 mL; LCI: mean difference 0.03,
      95% CI -0.32-0.25). CONCLUSIONS: EIT shows distinct differences in ventilation
      distribution between preterm and term-born infants, which cannot be detected by
      MBW. Although preterm infants are capable of dynamically maintaining overall
      functional residual volume and ventilation distribution, they show some spatial
      differences from fullterm infants.

PMID- 18810388
TI  - Randomised trial comparing ocular lubricants and polyacrylamide hydrogel
      dressings in the prevention of exposure keratopathy in the critically ill.
AB  - PURPOSE: To compare the cost and effectiveness of the two most popular forms of
      eye care in intensive care, ocular lubricant (Lacrilube) and polyacrylamide
      hydrogel dressings (Geliperm); for the prevention of exposure keratopathy in the
      critically ill. METHODS: A prospective randomised contralateral eye study was
      conducted at the Intensive Care Unit (ICU), Royal London Hospital, London, UK.
      Eighty eyes of 40 patients were recruited. Each patient received both Lacrilube
      and Geliperm allocated at random to different sides. A daily ophthalmology ward
      round was conducted. The outcome measures included the greatest palpebral
      aperture length, conjunctival oedema, and any exposure keratopathy. RESULTS:
      There was no statistically significant difference in the maximum corneal exposure
      score between the eyes treated with Lacrilube and Geliperm (P = 0.38). No
      significant difference in degree of chemosis or palpebral aperture was
      identified. CONCLUSIONS: Our data suggest that Geliperm is as effective as
      Lacrilube in the prevention of exposure keratopathy in the critically ill. We
      also note that nursing staff must be fully trained in its application for eye
      care.

PMID- 18810389
TI  - Out of the ring and into a sling: acute latissimus dorsi avulsion in a
      professional wrestler: a case report and review of the literature.
AB  - We present a 29-year-old professional wrestler who sustained a traumatic
      latissimus dorsi tendon rupture from its humeral insertion. To our knowledge,
      this report is the first to describe the use of two small anterior axillary
      incisions to repair a traumatic avulsion of the latissimus dorsi. Our new
      surgical approach is an alternative treatment for highly competitive, muscular
      athletes, while taking the associated nerves and cosmetic appearance into
      consideration.

PMID- 18810390
TI  - A correlation of time with meniscal tears in anterior cruciate ligament
      deficiency: stratifying the risk of surgical delay.
AB  - Two hundred and five patients with ACL rupture, who had been diagnosed pre
      operatively by either MRI scan or knee arthroscopy, had reconstructions between
      2003 and 2007. The diagnostic meniscal findings were compared with those at
      reconstruction, and any further damage along with time from diagnosis to
      reconstruction was recorded. Those patients with no meniscal damage at the time
      of diagnosis, and who had no further damage at surgery had a median time of 6
      months. This time was significantly different from those with no meniscal damage
      at diagnosis, but who were found subsequently to have sustained damage to one
      meniscus, when the median time was 11 months (P = 0.0017) or both menisci, when
      the median time was 32 months (P = 0.0184). For patients with solitary ACL
      rupture undergoing a trial of conservative management, an early and thorough
      assessment of functional stability is essential. If the instability is
      unacceptable, the patient should be informed of the time dependent risk to the
      menisci with further delay to surgical reconstruction.

PMID- 18810391
TI  - The immediate effect of navigation on implant accuracy in primary mini-invasive
      unicompartmental knee arthroplasty.
AB  - The success of unicompartmental knee arthroplasty (UKA) is highly dependent on
      the accuracy of the component alignment. Objective of the present study was to
      evaluate the immediate effect of image-free computer navigation technology on
      implant accuracy in primary mini-invasive UKA. This study reviews 40 patients
      with primary isolated arthritis of the medial compartment of the knee that
      underwent unicompartmental knee arthroplasty through a minimally invasive
      approach. A cohort of the 20 most recent consecutive UKA's implanted with
      standard instrumentation was followed by a cohort of the very first 20
      consecutive cases after conversion to the navigated technique. There was no
      variability regarding implant (Oxford meniscal unicompartmental knee system-
      Biomet Orthopedics, Inc., Warsaw, Indiana 46580, USA), surgeons and surgical
      technique, except for the use of the navigation system (Treon plus--Medtronic
      Inc., Minnesota, MI, USA). The axis alignment and accuracy of implant positioning
      was measured on postoperative long-leg standing radiographs and standard lateral
      X-rays with regard to the valgus angle and the coronal and sagittal component
      angle. In addition, preoperative deformities of the mechanical leg axis,
      tourniquet time, age, gender, and body mass index were correlated. Statistical
      analyses were performed using the SPSS 14.0 (SPSS Inc., Chicago, IL, USA)
      software package. Optimal implant alignment including all measurements in the
      desired angular range was significantly (P=0.041) higher in the navigated cohort.
      Navigation eliminated outliers in the frontal mechanical alignment and coronal
      orientation of the femoral component totally and significantly (P<0.02).
      Furthermore, navigation narrowed the range of outliers in all other planes of
      component orientation. There were no statistically significant differences in the
      mean numerical values between the cohorts, except for the frontal mechanical
      alignment (P<0.009) and coronal tibial alignment (P<0.037). The average
      tourniquet time was increased by 10.95 min in the navigated cohort. Our results
      indicate that navigation immediately improves accuracy of bone cuts and reduces
      the number of outliers with implementation in UKA.

PMID- 18810392
TI  - Potential pitfall in the microfracturing technique during the arthroscopic
      treatment of an osteochondral lesion.
AB  - Debridement and bone marrow stimulation of the subchondral bone is currently
      considered to be the primary surgical treatment of most osteochondral lesions of
      the talus. Different methods of bone marrow stimulation are used, including
      drilling, abrasion, and microfracturing. The latter has gained recent popularity.
      In this technical note we describe a potential pitfall in the microfracturing
      technique. The microfracture awl can easily create small bony particles on
      retrieval of the probe that may stay behind in the joint. It is emphasized that
      the joint should be carefully inspected and flushed at the end of each procedure,
      in order to prevent leaving behind any loose bony particles.

PMID- 18810393
TI  - Haloperidol and risperidone have specific effects on altered pain sensitivity in
      the ketamine model of schizophrenia.
AB  - RATIONALE: The ketamine (ket) model reflects features of schizophrenia as well as
      secondary symptoms such as altered pain sensitivity. OBJECTIVES: In the present
      study, we investigated the effect of subchronic oral treatment with haloperidol
      (hal, 0.075 mg/kg) and risperidone (ris, 0.2 mg/kg) on altered pain perception
      and locomotor activity in this model. RESULTS: In reaction to 5 mg/kg morphine,
      ket pretreated animals showed a diminished analgesic response. Hal had no
      analgesic effect per se, but the compound normalised the analgesic reaction to
      morphine in the ket pretreated animals. The effect of ris was complex. First,
      there was no analgesic effect per se, and control animals showed a dose-dependent
      increase in the analgesic index after morphine injection. In the ket group
      treated with ris, the analgesic response to 5 mg/kg morphine was attenuated and
      in response to 10 mg/kg analgesia was comparable with that measured in controls.
      The reduced analgesic effect was not due to pharmacokinetic differences in
      morphine metabolism. After administration via drinking water in saline-injected
      control animals, the hal blood serum concentration was 2.6 +/- 0.45 ng/ml. In ket
      injected animals, the mean serum concentration of hal amounted to 1.2 +/- 0.44
      ng/ml. In the experiment using ris, animals in the control group had higher ris
      serum concentrations compared with ket-injected animals. In control animals,
      morphine dose dependently decreased locomotor activity. This effect was
      significantly stronger in the ket pretreated groups. CONCLUSIONS: Hal and ris had
      different effects on altered pain sensitivity. It was hypothesised that these
      results are connected with alterations in dopamine D2 and mu opioid receptor
      binding.

PMID- 18810394
TI  - Expensive equipment--a guide to purchasing.

PMID- 18810396
TI  - Chronotype and time-of-day influences on the alerting, orienting, and executive
      components of attention.
AB  - Recent research on attention has identified three separable components, known as
      alerting, orienting, and executive functioning, which are thought to be subserved
      by distinct neural networks. Despite systematic investigation into their
      relatedness to each other and to psychopathology, little is known about how these
      three networks might be modulated by such factors as time-of-day and chronotype.
      The present study administered the Attentional Network Test (ANT) and a self
      report measure of alertness to 80 participants at 0800, 1200, 1600, and 2000
      hours on the same day. Participants were also chronotyped with a
      morningness/eveningness questionnaire and divided into evening versus
      morning/neither-type groups; morning chronotypes tend to perform better early in
      the day, while evening chronotypes show enhanced performance later in the day.
      The results replicated the lack of any correlations between alerting, orienting,
      and executive functioning, supporting the independence of these three networks.
      There was an effect of time-of-day on executive functioning with higher conflict
      scores at 1200 and 1600 hours for both chronotypes. The efficiency of the
      orienting system did not change as a function of time-of-day or chronotype. The
      alerting measure, however, showed an interaction between time-of-day and
      chronotype such that alerting scores increased only for the morning/neither-type
      participants in the latter half of the day. There was also an interaction between
      time-of-day and chronotype for self-reported alertness, such that it increased
      during the first half of the day for all participants, but then decreased for
      morning/neither types (only) toward evening. This is the first report to examine
      changes in the trinity of attentional networks measured by the ANT throughout a
      normal day in a large group of normal participants, and it encourages more
      integration between chronobiology and cognitive neuroscience for both theoretical
      and practical reasons.

PMID- 18810397
TI  - Starting insomnia treatment: the use of benzodiazepines versus z-hypnotics. A
      prescription database study of predictors.
AB  - PURPOSE: Drugs prescribed for the treatment of insomnia can be either
      benzodiazepine hypnotics or the newer z-hypnotics, zopiclone and zolpidem. This
      paper explores possible explanations for the choice made. METHODS: Data from the
      Norwegian Prescription Database covering the entire population was studied for
      incident users of hypnotics. Possible predictors were age, gender, previous
      psychotropic or analgesic drug use and prescriber speciality. RESULTS: Of the
      73,163 incident users of hypnotics, 3876 were prescribed benzodiazepine hypnotics
      in 2006. The strongest predictors for being prescribed benzodiazepines were
      previous use of anxiolytics [odds ratio (OR) 1.8, 95% confidence interval (CI)
      1.7-2.0] and male gender (OR 1.5, 95% CI 1.4-1.6). Other significant predictors
      were antipsychotic or opioid drug use and the prescriber being a psychiatrist.
      CONCLUSIONS: Z-hypnotics were commonly prescribed. Norwegian drug therapy
      recommendations also suggest a preference for z-hypnotics. The clear predominance
      of the shorter acting z-hypnotics may be due to the fact that only longer acting
      benzodiazepines are available in Norway. Reasons for prescribing benzodiazepines
      may be co-morbid psychiatric illness, such as anxiety, or a belief that
      benzodiazepine hypnotics are more effective than z-hypnotics.

PMID- 18810398
TI  - High absolute bioavailability of methylene blue given as an aqueous oral
      formulation.
AB  - PURPOSE: Methylene blue (MB) has recently been reevaluated for malaria treatment.
      With the aim of excluding treatment failures due to low bioavailability, we have
      investigated the absolute bioavailability of MB given as an aqueous oral
      formulation and its interaction with chloroquine (CQ). METHODS: A phase I study
      in 16 healthy individuals was performed as a monocenter prospective open
      randomized intra-individual cross-over comparison of MB single doses [50 mg
      intravenous (i.v.), 500 mg orally, separated by a 1-week wash-out]. After a
      second week, the group was split for a randomized parallel group comparison of CQ
      750 mg administered orally alone or combined with 500 mg MB orally. RESULTS: Mean
      MB plasma area under the substrate concentration-time curve (AUC 0-infinity) was
      7,639 +/- 3,384 ng/mL*h and 51,171 +/- 17,147 ng/mL*h after i.v. and oral
      administration, respectively (dosage 1:10), and 76,897 +/- 46,037 ng/mL*h after
      MB combined with CQ. The absolute bioavailability was 72.3 +/- 23.9%. Co
      administration with CQ significantly increased MB plasma concentrations (p <or=
      0.016); CQ kinetics remained unaffected. CONCLUSION: The absolute bioavailability
      of MB is high. Co-administration of MB and CQ increases plasma, but not whole
      blood MB concentrations.

PMID- 18810399
TI  - Clinical pharmacokinetics of penicillins in the neonate: a review of the
      literature.
AB  - BACKGROUND: Sepsis is common in neonates and a major cause of morbidity and
      mortality. Sixty percent of preterm neonates receive at least one antibiotic
      during the first week of life, with penicillins being the most frequently
      administered antibiotics. The clearance (Cl), serum half-life (t((1/2))) and
      volume of distribution (Vd) of penicillins are different in the neonate than in
      the adult. As such, the pharmacokinetics of penicillins need be studied in
      neonates in order to optimise therapy in this age class with these drugs.
      OBJECTIVES: The aim of this study was to review the published data on the
      pharmacokinetics of penicillins in the neonate in order to provide a critical
      analysis of the literature and, consequently, a useful tool in the hands of the
      physician. METHODS: The bibliographic search was performed electronically using
      the PubMed and EMBASE databases as search engines. An initial search was
      performed with the keywords "pharmacokinetics", "penicillins" and "neonates".
      Secondly, other searches were performed using the keywords "pharmacokinetics" and
      "neonates", followed by the name of a single antibiotic. The search included
      articles up to 2007. RESULTS: There have been few pharmacokinetic studies on the
      use of penicillins in neonates. The results from those few studies that have been
      carried out suggest that the Cl is reduced and t((1/2)) prolonged in the neonate
      as compared with the more mature infant. There is little variation in Vd during
      the first week of life. In the premature neonate, Cl is reduced compared to the
      full-term infant. As postnatal age proceeds, the Cl of penicillins increases.
      CONCLUSIONS: More pharmacokinetic studies are required to provide a sound
      scientific basis for planning a dosage regimen with penicillins in the neonate.

PMID- 18810400
TI  - Differences in complication rates among the centres in the SPACE study.
AB  - INTRODUCTION: Despite the high grade of standardisation of study protocols, there
      is still room for variability among the centres in specific treatment aspects. We
      evaluated the treatment risk in stent-protected angioplasty of the carotid versus
      endarterectomy (SPACE) associated with the specific patient enrollment rates of
      the centres. MATERIALS AND METHODS: The analysed endpoints were ipsilateral
      stroke or death [primary outcome event (pOE)] and any stroke or death [secondary
      outcome event (sOE)] until 30 days after treatment. A binary logistic regression
      analysis with random effects was performed separately for each treatment arm. The
      centres were secondarily categorised in three classes: I) > or = 25 patients
      enrolled, II) ten to 24 patients and III) <10 patients and a hierarchic log
      linear model was fitted to test the three-way interaction of treatment, number of
      patients per class and outcome. RESULTS: The random effects logistic regression
      analysis in the carotid artery stenting (CAS) arm proved a significant increase
      in pOE with decreasing number of patients enrolled (-0.0190 +/- 0.0085, p =
      0.025, deviance 35.7 with 32 df), whereas no such effect was found in the carotid
      endartectomy (CEA) arm (-0.010 +/- 0.008, p = 0.24, deviance 39.78 with 32 df).
      In the log linear model, there was a significant interaction between treatment,
      number of patients per centre and sOE (p = 0.023). The odds ratios for sOE in the
      enrollment classes (CAS vs. CEA) were 0.98 (95% CI 0.50-1.94, p = 0.95) for class
      I, 1.13 (95% CI 0.47-2.77, p = 0.77) for class II and 11.56 (95% CI 1.40-253.45,
      p = 0.01) for class III centres. CONCLUSION: Despite rigorous standardisation and
      quality requirements for operator qualification, there seemed to be a decrease in
      complication rate with increasing patient enrollment numbers in the CAS arm while
      this signal could not be detected in the CEA arm of SPACE.

PMID- 18810401
TI  - Vitamin D insufficiency/deficiency - a conundrum.

PMID- 18810402
TI  - Pediatric head trauma: the evidence regarding indications for emergent
      neuroimaging.
AB  - Traumatic brain injury (TBI) is a leading cause of childhood death and disability
      worldwide. In the United States, childhood head trauma results in approximately
      3,000 deaths, 50,000 hospitalizations, and 650,000 emergency department (ED)
      visits annually. Children presenting to the ED with seemingly minor head trauma
      account for approximately one-half of children with documented TBIs. Despite the
      frequency and importance of childhood minor head trauma, there exists no highly
      accurate, reliable and validated clinical scoring system or prediction rule for
      assessing risk of TBI among those with minor head trauma. At the same time, use
      of CT scanning in these children in recent years has increased substantially. The
      major benefit of CT scanning is early identification (and treatment) of TBIs that
      might otherwise be missed and result in increased risk of morbidity and
      mortality. Unnecessary CT imaging, however, exposes the child needlessly to the
      risk of radiation-induced malignancies. What constitutes appropriate criteria for
      obtaining CT scans in children after minor blunt head trauma remains
      controversial. Current evidence to guide clinicians in this regard is limited;
      however, large studies performed in multi-center research networks have recently
      been conducted. These studies should provide the foundation of evidence to guide
      CT decisions by clinicians, help identify TBIs in a timely fashion, and reduce
      unnecessary radiation exposure.

PMID- 18810403
TI  - Rickets or abuse?

PMID- 18810404
TI  - Evaluating the data concerning vitamin D insufficiency/deficiency and child
      abuse.

PMID- 18810405
TI  - Rickets or abuse, or both?

PMID- 18810406
TI  - Building bridges between radiology and emergency medicine: consensus conference
      on imaging safety and quality for children in the emergency setting. Proceedings
      of the ALARA conference. February 23-24, 2008. Orlando, Florida, USA.

PMID- 18810407
TI  - Standards for radiology interpretation and reporting in the emergency setting.
AB  - The radiologist plays a pivotal role in the medical management of injury and
      illness in both adults and children in the emergency setting. Although the
      primary role of the radiologist is to assist in establishing a correct diagnosis,
      the radiologist's responsibility goes well beyond simple detection and
      documentation. Communication is fundamental in assuring delivery of quality and
      safe health care. Lines of communication are most easily recognized between the
      radiologist and the patient's health-care provider (e.g., emergency department
      physician), but they are also becoming increasingly important between the
      radiologist and the patient. Radiologists must be familiar with both local and
      national practice guidelines related to the care of the patient in the emergency
      setting, in relation to both construction of the radiology report and appropriate
      communication of the results of radiologic studies. Familiarity with these
      aspects of the radiologists' responsibilities maximizes the chance of successful
      outcomes and minimizes the frequency of (and liability for) malpractice.

PMID- 18810408
TI  - Potential risks in radiology departments.
AB  - Pediatric patients in the Emergency Department (ED) often need diagnostic imaging
      examinations. These range from radiographs to fluoroscopic procedures to CT and
      MRI. Each of these examinations requires transportation and hand-offs (transfer
      of patient to different health care workers), and each carries inherent risks of
      the procedure itself. The following material will examine a variety of common
      situations that involve interaction between patients from the ED and the
      radiology department and describe potential risks and methods through which these
      risks can be minimized.

PMID- 18810409
TI  - Imaging utilization commentary: a radiology perspective.
AB  - To adhere to the ALARA concept, imaging should be limited to studies that
      actually contribute to the management of the patient. For example, by applying
      the Ottawa Ankle Rule and the Ottawa Knee Rule, fewer radiographs are required to
      evaluate ankle and knee trauma in children. Chest radiographs usually do not
      contribute to the management of children presenting with typical acute
      bronchiolitis or asthma, and they can be detrimental because consolidation
      resulting from retained secretions is interpreted as pneumonia and the child is
      started on antibiotics unnecessarily. Moreover, a radiograph of the abdomen has
      poor validity and reproducibility for the diagnosis of constipation. The
      Pediatric Emergency Care Applied Research Network (PECARN) and the Pediatric
      Emergency Research in Canada (PERC) are currently developing decision rules for
      the use of CT in the assessment of minor head injuries in children, which should
      reduce its utilization in this condition. PECARN is also developing a decision
      rule for the use of CT in the assessment of abdominal trauma in children. CT is
      frequently used for the diagnosis of appendicitis in children, but appendicitis
      can be diagnosed clinically. If imaging is required, appendicitis can often be
      diagnosed with US, and CT need only be used in the minority of cases where the
      diagnosis is still in doubt. Utilization guidelines for pediatric imaging studies
      obtained in children in the emergency setting can improve yield and help in the
      more efficient management of often scarce health care resources.

PMID- 18810410
TI  - Radiologic procedures, policies and protocols for pediatric emergency medicine.
AB  - Protocol development between radiology and pediatric emergency medicine requires
      a multidisciplinary approach to manage straightforward as well as complex and
      time-sensitive needs for emergency department patients. Imaging evaluation
      requires coordination of radiologic technologists, radiologists, transporters,
      nurses and coordinators, among others, and might require accelerated routines or
      occur at sub-optimal times. Standardized protocol development enables providers
      to design a best practice in all of these situations and should be predicated on
      evidence, mission, and service expectations. As in any new process, constructive
      feedback channels are imperative for evaluation and modification.

PMID- 18810411
TI  - Reflections of a patient safety officer.

PMID- 18810412
TI  - The radiology perspective: needs and tools for management of life-threatening
      events.
AB  - Studies have shown that life-threatening contrast agent reactions in adults are
      very rare, and even less common in children. The rarity of severe allergic
      reactions to contrast material challenges educators to achieve radiology resident
      competency in this setting. However, using a simulated anaphylactic contrast
      reaction paradigm, we have drawn two conclusions: (1) Residents are
      insufficiently prepared to recognize and manage these life-threatening events and
      (2) with an interactive, computer-based tool we can significantly improve
      resident performance in these situations. Simulation is a growing tool in
      medicine and allows standardized resident exposure to uncommon events in a
      setting that is conducive to resident education without fear of repercussions
      (see Ruddy and Patterson in this issue of Pediatric Radiology). More important,
      simulation provides a cornerstone in patient safety resident education without
      putting patients at risk.

PMID- 18810413
TI  - Improving patient safety in radiology: a work in progress.
AB  - The purpose of this paper is to share the experiences, including successes and
      failures, as well as the ongoing process of developing and implementing a safety
      program in a large pediatric radiology department. Building a multidisciplinary
      pediatric radiology safety team requires successful recruitment of team members,
      selection of a team leader, and proper and ongoing training and tools, and
      protected time. Challenges, including thorough examples, are presented on
      improving pediatric radiology safety intradepartmentally, interdepartmentally,
      and institutionally. Finally, some major challenges to improving safety in
      pediatric radiology, and healthcare in general, are presented along with
      strategies to overcome these challenges. Our safety program is a work in
      progress; this article is a personal account and the reader is asked for
      tolerance of its occasional subjective tone and contents.

PMID- 18810414
TI  - Medical simulation: a tool for recognition of and response to risk.
AB  - The use of simulation and team training has become an excellent tool to reduce
      errors in high-risk industry such as the commercial airlines and in the nuclear
      energy field. The health care industry has begun to use similar tools to improve
      the outcome of high-risk areas where events are relatively rare but where
      practice with a tactical team can significantly reduce the chance of bad outcome.
      There are two parts to this review: first, we review the rationale of why
      simulation is a key element in improving our error rate, and second, we describe
      specific tools that have great use at the clinical bedside for improving the care
      of patients. These cross different (i.e. medical and surgical) specialties and
      practices within specialties in the health care setting. Tools described will
      include the pinch, brief/debriefing, read-backs, call-outs, dynamic skepticism,
      assertive statements, two-challenge rules, checklists and step back (hold
      points). Examples will assist the clinician in practical daily use to improve
      their bedside care of children.

PMID- 18810415
TI  - The art of communication: strategies to improve efficiency, quality of care and
      patient safety in the emergency department.
AB  - The practice of pediatric emergency medicine (PEM) has been supported by
      wonderful advancements in diagnostic testing, particularly in medical imaging.
      One of the most remarkable has been CT, which has arguably become our most
      valuable diagnostic tool in the emergency department (ED). PEM specialists have
      grown increasingly aware of quality and safety concerns in the care of children
      in emergency medical settings, spurred in part by a rapid growth in ED
      utilization and significant overcrowding. In the midst of this comes the
      revelation that one of our most valued diagnostic tools might place our youngest
      patients at a significant risk for the development of fatal cancer. This article
      reinforces the fundamental importance of communication and teamwork as a means to
      promote patient care quality and safety in the ED, and it offers partnership
      strategies for PEM and pediatric radiology specialists to consider as they
      address these important concerns.

PMID- 18810416
TI  - 'Sleeping with the enemy?' Expectations and reality in imaging children in the
      emergency setting.
AB  - As an introduction to the ALARA conference titled "Building Bridges between
      Radiology and Emergency Medicine: Consensus Conference on Imaging Safety and
      Quality for Children in the Emergency Setting," it is important for us to
      understand the landscapes of both the pediatric radiology and emergency medicine
      subspecialties. Recognizing potentially different practice patterns, including
      perspectives on pediatric care, as well as shared and sometimes unique
      professional pressures, can help us identify common concerns and problems and
      facilitate the development of strategies aimed at correcting these issues.

PMID- 18810417
TI  - Bedside pediatric emergency evaluation through ultrasonography.
AB  - Bedside US has emerged as a valuable technology for the emergency department
      physician. It impacts clinical decision-making and the safety of procedures, and
      it decreases the time and increases the efficiency for completion of procedures.
      The portability, accuracy and noninvasive nature of US make it an ideal tool for
      the trained clinician. Bedside US can improve clinical decision-making for the
      pediatric patient by helping the clinician to identify critical pathology, direct
      therapeutic maneuvers and determine the futility of resuscitations. Many
      pediatric procedures, such as vascular access, lumbar puncture and bladder
      catheterization, are typically performed blindly. Bedside US enhances the success
      of procedures, minimizes complications and limits the number of attempts
      necessary to complete a procedure. Bedside US can be a valuable adjunct for
      complicated and time-sensitive disease processes such as ectopic pregnancy,
      testicular torsion and hypovolemia by providing information to guide diagnostic
      and therapeutic interventions that subsequently improve outcomes.

PMID- 18810418
TI  - Fundamentals of a patient safety program.
AB  - Thousands of people are injured or die from medical errors and adverse events
      each year, despite being cared for by hard-working, intelligent and well-intended
      health care professionals, working in the highly complex and high-risk
      environment of the American health care system. Patient safety leaders have
      described a need for health care organizations to make error prevention a major
      strategic objective while at the same time recognizing the importance of
      transforming the traditional health care culture. In response, comprehensive
      patient safety programs have been developed with the aim of reducing medical
      errors and adverse events and acting as a catalyst in the development of a
      culture of safety. Components of these programs are described, with an emphasis
      on strategies to improve pediatric patient safety. Physicians, as leaders of the
      health care team, have a unique opportunity to foster the culture and commitment
      required to address the underlying systems causes of medical error and harm.

PMID- 18810419
TI  - Standards for clinical evaluation and documentation by the emergency medicine
      provider.
AB  - Pediatric emergency medicine is full of challenges. When a pediatric patient has
      a poor outcome after treatment in an emergency department (ED), a malpractice
      lawsuit is likely to result. Pediatric emergency medicine (PEM) physicians might
      sometimes alter their medical care and practice "defensive medicine" in hopes of
      avoiding a malpractice lawsuit. Radiographs and other diagnostic studies might be
      ordered without true indications to "completely rule out" a diagnosis. This can
      result in excess radiation for a child. On the other hand, failure to order the
      appropriate study or misinterpretation of a radiographic study by a radiologist
      or an emergency physician can result in a malpractice lawsuit. PEM physicians
      must work cooperatively with radiologists to improve the care for children in the
      ED. Together these specialists can decide on appropriate studies for children in
      the ED, keep radiation exposure to a minimum and ensure proper management based
      on these studies.

PMID- 18810420
TI  - Contemporary imaging in abdominal emergencies.
AB  - Imaging is often a fundamental part in the evaluation of an injured or ill child.
      A variety of imaging modalities (radiography, angiography/fluoroscopy,
      sonography, CT, magnetic resonance imaging and scintigraphy) are among the
      options. CT is worth focused attention because of its usefulness in a variety of
      emergency department settings, its increasing use, and its potential radiation
      risks. CT plays an important role in the evaluation of traumatic and nontraumatic
      abdominal emergencies in children. Therefore, the goal of this paper is to review
      current imaging approaches and controversies in the evaluation of common acute
      abdominal emergencies. Through discussion of various modalities, especially CT in
      evaluation of abdominal pain and trauma, the relative advantages and
      disadvantages including radiation risk will be reviewed.

PMID- 18810421
TI  - The art of communication: strategies to improve patient and information flow :
      radiology perspective.
AB  - The art of communication involves understanding the needs of the person with whom
      one is interacting. The radiologist must be an expediter and a consultant. Face
      to-face, eyeball-to-eyeball communication is almost always best. Nonverbal
      communication must be aligned with verbal principles. The radiologist must build
      trust to have successful communication and fulfill the role of a consultant who
      adds value to a child's health care. This occurs most easily by increased
      visibility and face-to-face discussion.

PMID- 18810422
TI  - The ALARA concept in pediatric imaging: building bridges between radiology and
      emergency medicine: consensus conference on imaging safety and quality for
      children in the emergency setting, Feb. 23-24, 2008, Orlando, FL - Executive
      Summary.

PMID- 18810423
TI  - Panel discussion. Pediatric imaging in the emergency department.

PMID- 18810424
TI  - Rickets vs. abuse: a national and international epidemic.

PMID- 18810425
TI  - Natural selection in the TLR-related genes in the course of primate evolution.
AB  - The innate immune system constitutes the front line of host defense against
      pathogens. Toll-like receptors (TLRs) recognize molecules derived from pathogens
      and play crucial roles in the innate immune system. Here, we provide evidence
      that the TLR-related genes have come under natural selection pressure in the
      course of primate evolution. We compared the nucleotide sequences of 16 TLR
      related genes, including TLRs (TLR1-10), MYD88, TILAP, TICAM1, TICAM2, MD2, and
      CD14, among seven primate species. Analysis of the non-synonymous/synonymous
      substitution ratio revealed the presence of both strictly conserved and rapidly
      evolving regions in the TLR-related genes. The genomic segments encoding the
      intracellular Toll/interleukin 1 receptor domains, which exhibited lower rates of
      non-synonymous substitution, have undergone purifying selection. In contrast,
      TLR4, which carried a high proportion of non-synonymous substitutions in the part
      of extracellular domain spanning 200 amino acids, was found to have been the
      suggestive target of positive Darwinian selection in primate evolution. However,
      sequence analyses from 25 primate species, including eight hominoids, six Old
      World monkeys, eight New World monkeys, and three prosimians, showed no evidence
      that the pressure of positive Darwinian selection has shaped the pattern of
      sequence variations in TLR4 among New World monkeys and prosimians.

PMID- 18810426
TI  - The white-rot fungus Phanerochaete chrysosporium: conditions for the production
      of lignin-degrading enzymes.
AB  - Investigating optimal conditions for lignin-degrading peroxidases production by
      Phanerochaete chrysosporium (P. chrysosporium) has been a topic for numerous
      researches. The capability of P. chrysosporium for producing lignin peroxidases
      (LiPs) and manganese peroxidases (MnPs) makes it a model organism of lignin
      degrading enzymes production. Focusing on compiling and identifying the factors
      that affect LiP and MnP production by P. chrysosporium, this critical review
      summarized the main findings of about 200 related research articles. The major
      difficulty in using this organism for enzyme production is the instability of its
      productivity. This is largely due to the poor understanding of the regulatory
      mechanisms of P. chrysosporium responding to different nutrient sources in the
      culture medium, such as metal elements, detergents, lignin materials, etc. In
      addition to presenting the major conclusions and gaps of the current knowledge on
      lignin-degrading peroxidases production by P. chrysosporium, this review has also
      suggested further work, such as correlating the overexpression of the intra and
      extracellular proteins to the nutrients and other culture conditions to discover
      the regulatory cascade in the lignin-degrading peroxidases production process,
      which may contribute to the creation of improved P. chrysosporium strains leading
      to stable enzyme production.

PMID- 18810427
TI  - Simultaneous utilization of D-cellobiose, D-glucose, and D-xylose by recombinant
      Corynebacterium glutamicum under oxygen-deprived conditions.
AB  - Corynebacterium glutamicum R was metabolically engineered to broaden its sugar
      utilization range to D-xylose and D-cellobiose contained in lignocellulose
      hydrolysates. The resultant recombinants expressed Escherichia coli xylA and xylB
      genes, encoding D-xylose isomerase and xylulokinase, respectively, for D-xylose
      utilization and expressed C. glutamicum R bglF317A and bglA genes, encoding
      phosphoenolpyruvate:carbohydrate phosphotransferase system (PTS) beta-glucoside
      specific enzyme IIBCA component and phospho-beta-glucosidase, respectively, for D
      cellobiose utilization. The genes were fused to the non-essential genomic regions
      distributed around the C. glutamicum R chromosome and were under the control of
      their respective constitutive promoter trc and tac that permitted their
      expression even in the presence of D-glucose. The enzyme activities of resulting
      recombinants increased with the increase in the number of respective integrated
      genes. Maximal sugar utilization was realized with strain X5C1 harboring five
      xylA-xylB clusters and one bglF317A-bglA cluster. In both D-cellobiose and D
      xylose utilization, the sugar consumption rates by genomic DNA-integrated strain
      were faster than those by plasmid-bearing strain, respectively. In mineral medium
      containing 40 g l(-1) D-glucose, 20 g l(-1) D-xylose, and 10 g l(-1) D
      cellobiose, strain X5C1 simultaneously and completely consumed these sugars
      within 12 h and produced predominantly lactic and succinic acids under growth
      arrested conditions.

PMID- 18810428
TI  - Multiple gene-mediated NAD(P)H-dependent aldehyde reduction is a mechanism of in
      situ detoxification of furfural and 5-hydroxymethylfurfural by Saccharomyces
      cerevisiae.
AB  - Furfural and 5-hydroxymethylfurfural (HMF) are representative inhibitors
      generated from biomass pretreatment using dilute acid hydrolysis that interfere
      with yeast growth and subsequent fermentation. Few yeast strains tolerant to
      inhibitors are available. In this study, we report a tolerant strain,
      Saccharomyces cerevisiae NRRL Y-50049, which has enhanced biotransformation
      ability to convert furfural to furan methanol (FM), HMF to furan di-methanol
      (FDM), and produce a normal yield of ethanol. Our recent identification of HMF
      and development of protocol to synthesize the HMF metabolic conversion product
      FDM allowed studies on fermentation metabolic kinetics in the presence of HMF and
      furfural. Individual gene-encoding enzymes possessing aldehyde reduction
      activities demonstrated cofactor preference for NADH or NADPH. However, protein
      extract from whole yeast cells showed equally strong aldehyde reduction
      activities coupled with either cofactor. Deletion of a single candidate gene did
      not affect yeast growth in the presence of the inhibitors. Our results suggest
      that detoxification of furfural and HMF by the ethanologenic yeast S. cerevisiae
      strain Y-50049 likely involves multiple gene mediated NAD(P)H-dependent aldehyde
      reduction. Conversion pathways of furfural and HMF relevant to glycolysis and
      ethanol production were refined based on our findings in this study.

PMID- 18810429
TI  - The absence of effect of gene copy number and mRNA level on the amount of mAb
      secretion from mammalian cells.
AB  - Recombinant human antibody production represents a major growing class of
      biopharmaceuticals based on the technological progress within the last decades
      especially in CHO cells. The HIV neutralizing human monoclonal antibody 2F5 was
      developed as hybridoma from human lymphocyte preparations. In order to estimate
      the potential of recombinant 2F5-expressing CHO cells, we generated different
      recombinant CHO cell lines by varying regulatory sequences, the codon usage, the
      signal peptides, and the transfection technique. These 2F5-expressing cell lines
      were developed by selection of the best producer, clone homogeneity, and clone
      stability. The gene copy number of the clones differed significantly due to
      methotrexate amplification. In one cell line, we identified only one copy of
      heavy chain and two copies of light chain. Neither the gene copy number nor the
      promoter was found to influence the amount of transcript exclusively emphasizing
      the positioning effect of the transgene. Messenger RNA levels were highest in
      2F5/CO and may have resulted from a combination of the promoter and codon
      optimized sequences, but unexpectedly, the amount of secreted product was not
      elevated in this configuration. In our example, translational and post
      translational limitations are responsible for decreased antibody secretion.

PMID- 18810430
TI  - Overproduction of soluble recombinant transglutaminase from Streptomyces
      netropsis in Escherichia coli.
AB  - A novel microbial transglutaminase (TGase) from the cultural filtrate of
      Streptomyces netropsis BCRC 12429 (Sn) was purified. The specific activity of the
      purified TGase was 18.2 U/mg protein with an estimated molecular mass of 38 kDa
      by sodium dodecyl sulfate polyacrylamide gel electrophoresis analysis. The TGase
      gene of S. netropsis was cloned and an open reading frame of 1,242 bp encoding a
      protein of 413 amino acids was identified. The Sn TGase was synthesized as a
      precursor protein with a preproregion of 82 amino acid residues. The deduced
      amino acid sequence of the mature S. netropsis TGase shares 78.9-89.6% identities
      with TGases from Streptomyces spp. A high level of soluble Sn TGase with its N
      terminal propeptide fused with thioredoxin was expressed in E. coli. A simple and
      efficient process was applied to convert the purified recombinant protein into an
      active enzyme and showed activity equivalent to the authentic mature TGase.

PMID- 18810431
TI  - A new strain of Streptomyces avermitilis produces high yield of oligomycin A with
      potent anti-tumor activity on human cancer cell lines in vitro.
AB  - A new actinomycete strain, isolated from soil in China, strongly inhibited in
      vitro proliferation of human hepatoma, chronic myelogenous leukemia, and colonic
      carcinoma cell lines. The strain, designated L033, was identified as a strain of
      Streptomyces avermitilis based on cultural property, morphology, carbon source
      utilization, 16s rRNA gene analysis, and DNA-DNA relatedness studies. The
      anticancer component from L033 was purified to homogeneity by preparative
      positive-phase high-performance liquid chromatography and crystallization.
      Nuclear magnetic resonance and mass spectrometric analysis showed that this
      compound had the same structure as oligomycin A. Different with other reported
      naturally occurring strains of S. avermitilis, L033 produced high quantity of
      oligomycin A (maximal 1,461 microg/ml). Therefore, L033 was considered of great
      potential as an industrial oligomycin-A-producing strain.

PMID- 18810432
TI  - Ultrasound findings of the locked metacarpophalangeal joint.
AB  - The radiographs and sonographic findings of two cases of locked
      metacarpophalangeal joint secondary to tethering of the volar plate are
      described. The presence of osteophytes and the dynamic ultrasound assessment of
      the volar plate have provided confirmation of the clinical diagnosis prior to
      surgery.

PMID- 18810433
TI  - Generalized dysplasia epiphysealis hemimelica with contralateral sacro-iliac
      joint involvement.
AB  - Dysplasia epiphysealis hemimelica (or Trevor's disease) is a rare developmental
      bone dysplasia characterized by benign osteocartilaginous overgrowth involving
      one or multiple epiphyses, usually of a single lower extremity. It is classified
      as localized form, classical form (most common), and generalized form. In this
      report we describe a case of generalized form of dysplasia epiphysealis
      hemimelica with involvement of the contralateral sacroiliac joint, which is an
      extremely rare presentation.

PMID- 18810434
TI  - Os peroneum friction syndrome complicated by sesamoid fatigue fracture: a new
      radiological diagnosis? Case report and literature review.
AB  - Injuries to the peroneal tendons are relatively common worldwide but tendon
      rupture without significant trauma is uncommon. Ankle mechanics can be seriously
      affected by disruption of one or both of the peroneal tendons although complete
      rupture can also remain asymptomatic. Accessory ossicles are sesamoid bones and
      are common findings in routine radiology of the foot and ankle. Although in the
      vast majority these "os" are normal variants of anatomy, they can lead to painful
      syndromes and suffer fractures and even undergo degenerative changes in response
      to overuse and trauma. Although similar syndromes have been discussed in the
      surgical literature, there is a lack of literature describing the use of modern
      imaging in the accurate diagnosis and its subsequent assistance towards
      appropriate management of os peroneum friction syndrome complicated by sesamoid
      fatigue syndrome. This article presents the plain film, sonographic and magnetic
      resonance imaging findings in a case of os peroneum friction syndrome complicated
      by a sesamoid fatigue fracture as well as reviewing the pertinent literature.

PMID- 18810435
TI  - Extended MRI findings of intersection syndrome.
AB  - OBJECTIVE: The symptoms and physical findings of intersection syndrome have been
      well described in the clinical medical literature. However, the magnetic
      resonance imaging (MRI) findings in patients with intersection syndrome of the
      forearm have only recently been described in a small number of patients. We
      review our experience with imaging of intersection syndrome, describe previously
      unreported MRI findings, and emphasize modifications to MRI protocols for its
      evaluation. MATERIALS AND METHODS: Institutional review board approval was
      obtained for this retrospective review of patients with MRI findings consistent
      with intersection syndrome of the forearm during the period from January 2004 to
      September 2006. Six patients were identified, three males and three females, with
      an average age of 39.3 years. The MRI examinations were reviewed to assess signal
      abnormalities within and adjacent to the first and second dorsal extensor tendon
      compartments (DETC): tendinosis, peritendinous edema or fluid, muscle edema,
      subcutaneous edema, and juxtacortical edema. The overall longitudinal extent of
      signal alterations was measured as well as the distance from Lister's tubercle to
      the crossover of the first and second DETC. RESULTS: Review of the MRIs showed
      increased intrasubstance tendon signal suggesting tendinosis in two of the six
      patients, peritendinous edema or fluid in all six patients, muscle edema in five
      of the six patients, and subcutaneous edema in three of the six patients.
      Juxtacortical edema was seen in one patient. Peritendinous edema or fluid
      extended distally beyond the radiocarpal joint in three of the six patients. The
      average distance from Lister's tubercle to the crossover of the first and second
      DETC was 3.95 cm, in keeping with recently published data. CONCLUSION:
      Intersection syndrome is an uncommon MRI diagnosis. In addition to the previously
      described MRI findings of edema adjacent to the first or second DETC, possibly
      with proximal extension and subcutaneous edema, we have identified additional
      abnormalities: tendinosis, muscle edema, and juxtacortical edema. In addition,
      our review shows that first and second DETC signal abnormalities in patients with
      intersection syndrome are not necessarily limited to the site of crossover but
      can extend distally beyond the radiocarpal joint. As standard wrist protocols may
      not include the area of intersection between the first and second DETC, coverage
      may need to be extended to the mid-forearm.

PMID- 18810436
TI  - MR features of a giant cyamella in a patient with osteoarthritis: presentation,
      diagnosis and discussion.

PMID- 18810437
TI  - Deferasirox in pyruvate kinase deficiency.

PMID- 18810438
TI  - [Expression of activated leukocyte cell adhesion molecule in breast cancer.
      Predictability of the response to taxane-free chemotherapy].
AB  - AIMS: Activated leukocyte cell adhesion molecule (ALCAM) is a cell surface
      immunoglobulin expressed in breast cancer (BC) and is assumed to be implicated in
      tumourigenesis and tumour progression. The importance of the adhesion molecule
      ALCAM for the response to taxane-free adjuvant chemotherapy was investigated.
      MATERIALS AND METHODS: Tissue specimens from 162 primary breast cancer patients
      were analyzed. Immunohistochemical staining (IHC) and Western blots (WB) were
      performed using monoclonal antibody against ALCAM. Relative protein amounts in WB
      bands were determined densitometrically. ALCAM mRNA expression was evaluated by
      microarray analysis (Affymetrix). RESULTS: In the normal breast ALCAM is
      expressed in luminal and basal epithelial cells. In BC samples, WB analysis
      showed a significant positive correlation of ALCAM levels with estrogen receptor
      status (p=0.04). For patients who received a taxane-free chemotherapy, a high
      ALCAM expression was predictive for a good response to chemotherapy. Median mRNA
      expression of ALCAM was 4.5-fold higher in patients alive at the time of follow
      up compared to those who died of breast cancer. CONCLUSIONS: Higher ALCAM
      expression showed a positive correlation with estrogen receptor status and is a
      useful predictive marker for the response to taxane-free chemotherapy.

PMID- 18810439
TI  - [Pathology and pathologists in fiction revisited].
AB  - Pathology and pathologists are rarely the subjects of works of fiction. In the
      existing sources, the kind of representation naturally depends on the occupations
      and attitudes of the respective authors. The surgeon and gynecologist Carl Ludwig
      Schleich recollected Rudolf Virchow's free and easy handling of an autopsy
      assistant and his simultaneous understanding for a mourning husband. The
      dermatologist Gottfried Benn processed his disturbing impressions of pathology as
      an expressionistic dialogue between professor and students, with a violent
      ending. The writer and dramatic adviser Gunther Weisenborn recalled unpleasant
      details about the autopsy course in his earlier medical studies, which he linked
      with individual views about the life of a deceased young woman. Praise, so to
      speak, to the dissecting pathologist have been sensitively written by the lawyer
      Maxence van der Meersch and by the surgeon Peter Bamm. Finally, the bestselling
      novelist Arthur Hailey gives an excellent fictional portrayal of the microscopic
      pathologist in The Final Diagnosis.

PMID- 18810440
TI  - [Molecular pathogenesis. Its importance in targeted therapy in colorectal
      cancer].
AB  - Colorectal cancer has the second highest mortality of all cancers in Germany. In
      spite of advances in surgical and chemotherapeutic treatment, efficient new
      therapies need to be developed. In recent years, advances have been achieved by
      novel targeted therapies that are specifically directed against altered signaling
      pathways of malignant cells. Colorectal cancers represent a heterogeneous tumor
      entity, and response to targeted therapies varies individually. About 15% of
      colorectal carcinomas are characterized by a deficient DNA mismatch repair system
      and microsatellite instability (MSI). These MSI cancers apparently have a
      decreased sensitivity to chemotherapy and frequently show evidence of a
      pronounced anti-tumoral immune response of the host. This immune response is
      likely to be mediated by a high number of tumor-specific antigens generated
      during MSI tumorigenesis. Interventions specifically targeting these antigens may
      be the basis for novel therapeutic strategies in MSI colorectal cancer and will
      be evaluated in clinical trials.

PMID- 18810441
TI  - [Acanthamoeba meningoencephalitis: a case in an adolescent female patient with
      systemic lupus erythematosus].
AB  - Meningoencephalitis caused by Acanthamoeba spp . is a rare opportunistic
      infection, difficult to diagnose and difficult to treat, which causes death in
      almost all cases. We report the neuropathologic findings of a 16-year-old girl
      with systemic lupus erythematosus (SLE) treated with immunosuppression who died
      of fulminant Acanthamoeba meningoencephalitis. Neuropathologic examination
      revealed multiple supratentorial and infratentorial hemorrhagic necrotizing
      lesions with encephalitis and vasculitis with mixed inflammatory infiltrates,
      fibrinoid necrosis of vessel walls, and local leptomeningitis. Acanthamoeba in
      the lesions may be misinterpreted as macrophages. Taking them into differential
      diagnostic consideration, cytological differences should be detected, and
      relevant additional stains for reliable differentiation of these cells can be
      performed. To our knowledge, this is the first published case of Acanthamoeba
      meningoencephalitis in a patient with SLE in Germany.

PMID- 18810442
TI  - [Meningiomas: multiparametric approach for risk stratification and grading].
AB  - The prognosis of the generally benign meningiomas is mainly an issue of the
      likelihood of recurrence, which increases with WHO grade (7-20% in WHO grade I,
      29-40% in WHO grade II, and 50-78% in WHO grade III meningiomas). Among clinical
      parameters the most important prognostic factor is the completeness of
      neurosurgical tumor resection. Among histopathological prognostic parameters the
      mitotic activity is the most important one. As the cutoffs of the mitotic index
      (MI) are defined for each grade by the WHO classification of brain tumors and
      because the MI can be applied as the sole grading criterion, the reliable and
      reproducible assessment of the MI is crucial for an appropriate risk
      stratification. This is provided by immunohistochemical mitosis markers, i.e.,
      phospho-histone H3 (PHH3). The PHH3 method is superior to the conventional
      mitosis counting method and therefore allows a more reliable risk stratification.
      The Ki-67 labeling index provides additional prognostic information, especially
      in prognostically ambiguous meningiomas. Cytogenetically, the deletion of the
      short arm of one chromosome 1 (1p-) is an unfavorable prognostic parameter and is
      correlated with a high risk of recurrence. The enzyme reaction for alkaline
      phosphatase (ALPL) is a fast and efficient screening method, which strongly
      indicates an intact chromosome 1 in cases with a positive enzyme reaction.

PMID- 18810443
TI  - Immunophenotyping without antibodies. New perspectives for lymphoma
      characterization.
AB  - AIMS: Accurate classification of haematological malignancies is a prerequisite
      for their correct diagnosis, prognosis and therapy. Clear classification of
      lymphomas is often hindered by the limited number of available cell surface
      protein markers that are suitable for immunophenotyping. A systematic and
      quantitative analysis of cell surface proteins is thus required to identify new
      protein markers on lymphoma subtypes in an unbiased and discovery-driven
      approach. METHODS: Nine Hodgkin and non-Hodgkin B cell lines of diffuse large
      cell type and mediastinal type were investigated by cell surface capture (CSC)
      technology, a mass spectrometry-based method to identify cell surface
      glycoproteins. Selected proteins are verified by antibody-based methods,
      including flow cytometry and immunohistochemistry on cell line arrays. RESULTS: A
      total of 747 predicted transmembrane proteins were identified from all cell
      lines, including 142 CD (cluster of differentiation) annotated proteins. A group
      of differentially expressed cell surface glycoproteins between Hodgkin and non
      Hodgkin B cell lines was revealed via quantitative CSC technology. In addition to
      classical and expected CD molecules such as CD20 and CD30, less frequently
      expressed molecules such as CD2 on Hodgkin lymphoma (HL) cell lines were
      identified by CSC and verified by immunohistochemistry in cell lines and primary
      lymphoma tissue. A panel of CSC-identified differentiation glycoprotein
      candidates is currently under investigation on tissue microarrays (TMAs) from
      patient samples.

PMID- 18810444
TI  - [Biobanking and Biomolecular Resources Research Infrastructure (BBMRI).
      Implications for pathology].
AB  - High quality human biological samples (e.g. blood, tissue or DNA) with
      associated, well documented clinical and research data are key resources for
      advancement of life sciences, biotechnology, clinical medicine, drug development
      and also molecular pathology. Millions of samples of diseased tissues have been
      collected in the context of routine histopathological diagnosis and are stored in
      the archives of hospitals and institutes of pathology. A concerted effort is
      necessary to overcome the current fragmentation of the European biobanking
      community in order to tap the full research potential of existing biobanks. A pan
      European research infrastructure for biobanking and biomolecular resources
      (BBMRI) is currently in its planning phase. The mission is to link and provide
      access to local biobanks of different formats, including tissue collections,
      harmonize standards, establish operational procedures which properly consider
      ethical, legal, societal aspects, and to secure sustainable funding. Pathology
      plays a key role in development and administration of tissue banks and is, thus,
      a major partner for collaboration, expertise and construction of this pan
      European research infrastructure.

PMID- 18810445
TI  - [Novel prognostic marker in invasive breast cancer. ITIH5 expression is abrogated
      by aberrant promoter methylation].
AB  - We have recently characterized ITIH5 as a new extracellular matrix protein that
      exhibits clear expression loss in a variety of human tumour entities, including
      breast cancer. The aim of the present study was to decipher the molecular cause
      of ITIH5 expression loss in breast cancer and to learn more about the possible
      role of this molecule in cancer diseases. ITIH5 protein expression was found to
      be strongly reduced in 42% of invasive breast carcinomas-interestingly, with
      significant association with poor patient outcome. ITIH5 promoter methylation was
      frequently detected in breast cell lines and in primary carcinomas (40%), and it
      was functionally correlated with loss of ITIH5 mRNA expression. Moreover, ITIH5
      promoter methylation was also significantly associated with poor clinical patient
      outcome and also with the occurrence of lymph node and distant metastases. In
      conclusion, we propose that ITIH5 may represent a novel metastasis repressor in
      human breast cancer. Both ITIH5 protein expression and ITIH5 promoter methylation
      may serve as prognostic biomarkers, thereby helping improve clinical patient
      outcome.

PMID- 18810446
TI  - [Molecular targets for colon cancer. VEGF, EGFR - and what else?].
AB  - Colorectal cancer (CRC) is the second most common cancer in Germany; there are
      more than 70,000 new cases annually. It is most commonly a disease of the
      elderly, and its relative and absolute frequency has risen during the last
      decades. CRC remains a major clinical and health economy challenge. Progress has
      been made in patient management and CRC treatment. Screening colonoscopy was
      introduced in Germany in 2002, and five new therapeutic agents have been approved
      since 2001, i.e. capecitabine, oxaliplatin, cetuximab, bevacizumab and
      panitumumab; guidelines have been published, and 48 interdisciplinary CRC centres
      have been certified in Germany in compliance with DIN EN ISO 9001:2000. Despite
      these advancements, targeted treatment of CRC is still in its infancy. Until
      2007, no predictive biomarkers were used to tailor the adjuvant or palliative
      chemotherapy of CRC. KRAS genotyping was recently introduced as predictive
      biomarker, since only tumors carrying a wildtype were found to respond to
      treatment with panitumumab. Among the tumors with KRAS wildtype, only 40-53%
      (equivalent to 20-30% of all CRC patients) will benefit from treatment, and the
      remainder are still enrolled for "non-targeted" treatment. Thus there is still a
      great need for predictive biomarkers that are able to tailor patient treatment at
      different stages of the disease.

PMID- 18810447
TI  - [Glycosphingolipids Gb3 and iGb3. In vivo roles in hemolytic-uremic syndrome and
      iNKT cell function].
AB  - The glycosphingolipids globotrihexosylceramide (Gb3, CD77) and
      isoglobotrihexosylceramide (iGb3) are isomers differing only in one glycosidic
      bond and have been implicated in several processes of the innate and adaptive
      immune system. AIMS: 1) To verify the function of Gb3 in the pathogenesis of
      hemolytic-uremic syndrome as the cellular receptor responsible for cytotoxicity
      caused by verotoxin (VT) elaborated by Shigella and certain strains of E.coli. 2)
      To investigate in vivo the previously implicated function of iGb3 as the
      endogenous lipid ligand responsible for positive selection of invariant natural
      killer T-cells (iNKT), which have an essential regulatory function in infection,
      tumor rejection and tolerance. METHODS: Generation of mice deficient in Gb3 and
      iGb3 synthesizing enzymes and VT injection into Gb3-deficient mice. Analysis of
      iNKT cell development and function by flow cytometry and by administration of the
      exogenous agonist alpha-galactosylceramide in iGb3-deficient mice. RESULTS: For
      1) Gb3-deficient mice were insensitive to otherwise lethal doses of VT, and 2)
      iGb3-deficient mice showed normal numbers of iNKT cells. Furthermore the function
      of iNKT cells evolving in iGb3-deficient mice was unaffected. CONCLUSIONS: 1) Gb3
      is the cellular receptor mediating verotoxin cytotoxicity in haemolytic-uremic
      syndrome. 2) In contrast to previous indirect implications, iGb3 cannot be
      regarded as an endogenous ligand responsible for the positive selection of iNKT
      cells.

PMID- 18810448
TI  - Thymic enlargement in a patient with juvenile idiopathic arthritis during
      etanercept therapy.
AB  - Tumor necrosis factor (TNF) alpha inhibitors are effective in the treatment of
      inflammatory rheumatic diseases. Despite their effectiveness, anti-TNF drugs have
      some drawbacks such as severe adverse effects including infections and possibly
      lymphoproliferative disorders. In this report we described a case of juvenile
      idiopathic arthritis patient who developed thymic enlargement (true thymic
      hyperplasia), mediastinal lymphadenopathy and pleurisy associated with systemic
      symptoms under Etanercept treatment. The clinical presentation was highly
      suggestive of malignancy and the patient underwent diagnostic mediastinoscopy
      with biopsy.

PMID- 18810449
TI  - Multineuropathy in a patient with HBV infection, polyarteritis nodosa and celiac
      disease.
AB  - We report on the first association of celiac disease, polyarteritis nodosa and
      HBV infection in a patient who developed a neuropathy. On admission his general
      and neurological conditions were severely compromised. Haematological test
      revealed HBV infection and high levels of antibodies to tissue transglutaminase,
      endomysium, gliadin. EMG showed sensory-motor asymmetric axonal neuropathy. A
      sural nerve biopsy revealed fibre loss, axonal degeneration with asymmetrical
      distribution and fascicular ischaemia. A duodenal biopsy was consistent with
      celiac disease. The patient was treated with immunosuppressive and antiviral
      therapy, and gluten-free diet with good result. Celiac disease can be related to
      a higher risk of autoimmune disorders and may have contributed to the development
      of multineuropathy in this patient.

PMID- 18810450
TI  - Primary antiphospholipid antibody syndrome: a case with bilateral sudden
      sensorineural hearing loss.

PMID- 18810451
TI  - MRI staging of low rectal cancer.
AB  - Low rectal tumours, especially those treated by abdominoperineal excision (APE),
      have a high rate of margin involvement when compared with tumours elsewhere in
      the rectum. Correct surgical management to minimise this rate of margin
      involvement is reliant on highly accurate imaging, which can be used to plan the
      planes of excision. In this article we describe the techniques for accurate
      magnetic resonance imaging (MRI) assessment and a novel staging system for low
      rectal tumours. Using this staging system it is possible for the radiologist to
      demonstrate accurately tumour-free planes for surgical excision of low rectal
      tumours.

PMID- 18810452
TI  - Ascending aorta measurements as assessed by ECG-gated multi-detector computed
      tomography: a pilot study to establish normative values for transcatheter
      therapies.
AB  - The aim of this study was to provide an insight into normative values of the
      ascending aorta in regards to novel endovascular procedures using ECG-gated multi
      detector CT angiography. Seventy-seven adult patients without ascending aortic
      abnormalities were evaluated. Measurements at relevant levels of the aortic root
      and ascending aorta were obtained. Diameter variations of the ascending aorta
      during cardiac cycle were also considered. Mean diameters (mm) were as follows:
      LV outflow tract 20.3 +/- 3.4, coronary sinus 34.2 +/- 4.1, sino-tubular junction
      29.7 +/- 3.4 and mid ascending aorta 32.7 +/- 3.8 with coefficients of variation
      (CV) ranging from 12 to 17%. Mean distances (mm) were: from the plane passing
      through the proximal insertions of the aortic valve cusps to the right brachio
      cephalic artery (BCA) 92.6 +/- 11.8, from the plane passing through the proximal
      insertions of the aortic valve cusps to the proximal coronary ostium 12.1 +/-
      3.7, and between both coronary ostia 7.2 +/- 3.1, minimal arc of the ascending
      aorta from left coronary ostium to right BCA 52.9 +/- 9.5, and the fibrous
      continuity between the aortic valve and the anterior leaflet of the mitral valve
      14.6 +/- 3.3, CV 13-43%. Mean aortic valve area was 582.0 +/- 131.9 mm(2). The
      variation of the antero-posterior and transverse diameters of the ascending aorta
      during the cardiac cycle were 8.4% and 7.3%, respectively. Results showed large
      inter-individual variations in diameters and distances but with limited intra
      individual variations during the cardiac cycle. A personalized approach for
      planning endovascular devices must be considered.

PMID- 18810453
TI  - Low-dose helical computed tomography (CT) in the perioperative workup of
      adolescent idiopathic scoliosis.
AB  - The study aims were to estimate the radiation dose in patients examined with low
      dose spine CT and to compare it with that received by patients undergoing
      standard CT for trauma of the same region, as well as to evaluate the impact of
      dose reduction on image quality. Radiation doses in 113 consecutive low dose
      spine CTs were compared with those in 127 CTs for trauma. The inter- and
      intraobserver agreement in measurements of pedicular width, and vertebral
      rotation, measurements of signal-to-noise ratio and assessment of hardware status
      were the indicators in the evaluation of image quality. The effective dose of the
      low dose spine CT (0.37 mSv) was 20 times lower than that of a standard CT for
      trauma (13.09 mSv). This dose reduction conveyed no impact on image quality. This
      low dose spine CT protocol allows detailed evaluation that is necessary for
      preoperative planning and postoperative evaluation.

PMID- 18810454
TI  - Clinical value of MRI liver-specific contrast agents: a tailored examination for
      a confident non-invasive diagnosis of focal liver lesions.
AB  - Screening of the liver for hepatic lesion detection and characterization is
      usually performed with either ultrasound or CT. However, both techniques are
      suboptimal for liver lesion characterization and magnetic resonance (MR) imaging
      has emerged as the preferred radiological investigation. In addition to
      unenhanced MR imaging techniques, contrast-enhanced MR imaging can demonstrate
      tissue-specific physiological information, thereby facilitating liver lesion
      characterization. Currently, the classes of contrast agents available for MR
      imaging of the liver include non-tissue-specific extracellular gadolinium
      chelates and tissue-specific hepatobiliary or reticuloendothelial agents. In this
      review, we describe the MR features of the more common focal hepatic lesions, as
      well as appropriate imaging protocols. A special emphasis is placed on the
      clinical use of non-specific and liver-specific contrast agents for
      differentiation of focal liver lesions. This may aid in the accurate diagnostic
      workup of patients in order to avoid invasive procedures, such as biopsy, for
      lesion characterization. A diagnostic strategy that considers the clinical
      situation is also presented.

PMID- 18810455
TI  - Evaluation of angiographic computed tomography in the follow-up after
      endovascular treatment of cerebral aneurysms--a comparative study with DSA and
      TOF-MRA.
AB  - Following coil embolization of intracranial aneurysms, many centers perform at
      least one digital subtraction angiography (DSA) continuing with time-of-flight
      magnetic resonance angiography (TOF-MRA). Angiographic computed tomography (ACT)
      provides high-resolution data from a rotational acquisition of a c-arm-mounted
      flat panel detector. This study evaluates possible advantages of applying ACT in
      aneurysm follow-up. In 22 patients DSA examinations with a rotational acquisition
      were performed. Rotational data were processed into an isotropic high-resolution
      volume. TOF-MRA was performed the day before DSA. Three experienced
      neuroradiologists performed a rating of the occlusion rate and a subjective
      method comparison. Weighted kappa statistics were calculated to assess the level
      of interobserver agreement. Compared to DSA, the diagnostic value of ACT as well
      as of TOF-MRA was rated to be inferior, although the sensitivity of detecting
      residual necks was higher with both techniques. Compared to TOF-MRA, ACT achieves
      favorable ratings only in aneurysms after stent-remodeling. Interobserver
      agreement was high for all techniques. Ratings of the occlusion rate correlated
      highly between all observers (r>0.85, p<0.001, respectively). In selected
      patients ACT can add valuable diagnostic information to DSA. TOF-MRA remains a
      highly sensitive method for aneurysm follow-up.

PMID- 18810456
TI  - Risk factors for nephrolithiasis in children.
AB  - OBJECTIVE: The aim of this study is to evaluate the clinical outcome in children
      with urinary calculi, to detect risk factors for nephrolithiasis in childhood.
      MATERIAL AND METHODS: This retrospective study comprised 62 pediatric
      nephrolithiasis patients who have come for routine follow-up visits between the
      dates of January 2002-August 2006 (48% girls and 52% boys). RESULTS: The mean age
      of the patients was 8.8 +/- 4.5 years (1-16 years). Hypercalciuria was found in
      25 (40%) patients. The mean urinary calcium excretion for hypercalciuric patients
      was 5.7 +/- 1.2 mg/kg (4.8 mg/kg per day). In our hypercalciuric patients 15
      (60%) children had abdominal or flank pain, seven (28%) patients macroscopic
      hematuria and three (12%) dysuria. Hypocitraturia is the second important risk
      factor for nephrolithiasis. Urinary calcium excretion showed a positive
      correlation with the stone size (r = 0.482, P = 0.043). A positive correlation
      was found between recurrent urinary tract infection (UTI) and hypercalciuria (r =
      0.528, P = 0.017). Urinary citrate excretion showed a negative correlation with
      recurrent UTI (r = -0.503, P = 0.024). Hyperuricaciduria, hyperoxaluria were
      found to have no effect on the stone size and UTI of the patients. Stones were
      disintegrated with ESWL in two patients, endoscopic interventions were used in
      one patient and two underwent an open surgical procedure. CONCLUSION: All
      children with nephrolithiasis should have a metabolic screen. Children with a
      positive family history and consanguinity should be followed carefully with
      respect to metabolic abnormalities.

PMID- 18810457
TI  - [Ophthalmological screening via a hospital boat: field study for planning future
      health care services in remote villages at the Volta Lake in Ghana].
AB  - BACKGROUND: A maiden voyage on a hospital boat was carried out to determine the
      spectrum of ophthalmological diseases in a rural and secluded area on the Volta
      Lake in Ghana in order to improve future health care services. PATIENTS AND
      METHODS: Portable water, electricity, and an operating theatre were available on
      the hospital boat. Visual acuity was determined using Snellen E charts, and Lea
      boards were used in children up to the age of 4 years. The anterior segments were
      examined using hand held slit lamps. After pupil dilation indirect binocular
      ophthalmoscopy was performed and tonometry was carried out using a Perkins
      tonometer RESULTS: A total of 1,246 citizens were examined. The mean age was 23.7
      years and the mean visual acuity was 6/6 (log MAR 0.0+/-0.3. The main cause of
      blindness was a cataract with 45.8%, followed by pathological conditions of the
      optic disc with 29.2%. CONCLUSIONS: The hospital boat is suitable for screening
      and for carrying out minor extraocular operations. Looking just at the technical
      aspect, it is possible to perform major intraocular operations on the hospital
      boat. However, due to the lack of immediate follow-up visits, it is advisable to
      carry out major operations in the next eye clinic on shore.

PMID- 18810458
TI  - [Anterior ischemic optic neuropathy: Etiology, pathogenetic mechanisms and
      therapy].
AB  - Ischemic optic neuropathy is caused by ischemia of the optic nerve head in the
      region of the lamina cribrosa. Differentiation is made between arteritic (AION)
      and nonarteritic (NAION) forms. AION is the most common ophthalmological
      manifestation of giant cell arteritis and is usually well controlled with
      systemic steroid therapy. Temporal artery biopsy for confirmation of the
      diagnosis is mandatory. NAION is not a disease entity but rather the common
      pathogenetic pathway of a large variety of diseases and conditions and is often
      the result of several interacting factors. For this reason, there is no "standard
      therapy" for NAION. Careful interdisciplinary work up in NAION frequently reveals
      previously unrecognized diseases requiring treatment according to internal
      medicine standards. Adequate treatment frequently results in improvement of the
      affected eye and reduced risk of NAION in the other eye or of brain infarction.

PMID- 18810459
TI  - Olfactory discrimination of aliphatic odorants at 1 ppm: too easy for CD-1 mice
      to show odor structure-activity relationships?
AB  - Using an operant conditioning paradigm we tested the ability of CD-1 mice to
      discriminate between 25 odorants comprising members of five homologous series of
      aliphatic odorants (C4-C8) presented at a gas phase concentration of 1 ppm. We
      found (a) that all mice significantly discriminated between all 50 stimulus pairs
      that involved odorants sharing the same functional group, but differing in carbon
      chain length, as well as between all 50 stimulus pairs that involved odorants
      sharing the same carbon chain length but differing in functional group, (b) a
      significant negative correlation between discrimination performance and
      structural similarity of odorants in terms of differences in carbon chain length
      with the acetic esters and the 2-ketones, but not with the 1-alcohols, n
      aldehydes, and n-carboxylic acids tested, and (c) that odorant pairs differing in
      functional group were significantly better discriminated than odorant pairs
      differing in carbon chain length. These findings demonstrate that CD-1 mice have
      excellent discrimination ability for structurally related aliphatic odorants,
      that correlations between discrimination performance and structural similarity of
      odorants are odorant class-specific rather than a general phenomenon, and that
      both carbon chain length and type of functional group play an important role for
      odor quality coding in mice.

PMID- 18810461
TI  - Optic nerve sheath ultrasound in the assessment of paediatric hydrocephalus.
AB  - OBJECTS: Optic nerve sheath diameter has been linked with intracranial pressure
      in previous studies. Measurement of sheath diameter using transorbital ultrasound
      is proposed as a clinical assessment indicator of developing hydrocephalus in the
      paediatric population. METHODS: A retrospective review of optic nerve sheath
      ultrasound examinations performed in a clinical setting between 2000 and 2006 for
      assessment of hydrocephalus in a single institution. RESULTS: A total of 331
      examinations were performed in 160 patients over the study period. A satisfactory
      image was possible in all cases. Sheath diameters were correlated with clinical
      case data from concurrent case records. CONCLUSION: Transorbital ultrasound is a
      reproducible, non-invasive technique for the assessment of optic nerve sheath
      diameter and is well tolerated in children. Our series revealed asymptomatic
      baseline value higher than in previous reports. Variation from individual case
      asymptomatic baseline was the most sensitive variable in the series in
      determining development of hydrocephalus. This technique is felt to be a useful
      adjunct in the assessment of hydrocephalus in the paediatric neurosurgical
      population.

PMID- 18810462
TI  - Inversion appendectomy acting as a lead point for intussusception.
AB  - A case of ileocecal intussusception following inversion appendectomy during a
      Ladd's procedure for malrotation is presented. In this case, the inverted
      ischemic appendiceal remnant was presumed to have acted as the leadpoint for the
      intussusception. The advantages and complications of inversion appendectomy,
      along with technical considerations are discussed.

PMID- 18810463
TI  - The route of the catheter directly affects the volume needed in experimental
      corrosive esophagitis.

PMID- 18810464
TI  - Thoracopagus parasites in two sets of twins: evidence for the fusion theory.
AB  - We report two sets of parasitic twins attached in the thoracic region. Exomphalos
      major in the autosite was present in both cases. While in case 1, the autosite
      could be salvaged after easier dissection, in case 2, the autosite could not be
      salvaged due to the presence of the life-threatening anomalies. The presence of a
      right-angled communication between the gastrointestinal tracts of the autosite
      and the independent tactile responses of the parasite from that in the autosite
      supports the 'fusion theory' to explain the fusion of the embryos that could have
      led to this defect. The presence of the ano-rectal malformation and common bile
      duct dilatation exclusively in the parasite appears to be the result of the
      abnormalities in the endodermal-mesodermal interactions, probably due to the
      relative positioning of the parasite with respect to the autosite.

PMID- 18810465
TI  - Primary Burkitt lymphoma presenting as a solitary rectal polyp in a child.
AB  - Non-Hodgkin lymphoma (NHL) accounts for approximately 60% of all lymphomas in
      children and adolescents. It represents 8-10% of all malignancies in children
      aged between 5 and 19 years. Primary rectal lymphoma in childhood is extremely
      rare. This report focuses on the importance of considering the possibility of
      malignancy in rectal polyps. We report a 5-year-old girl with fresh rectal
      bleeding who was admitted in our clinic. In physical exam, we found a single
      pedicled polyp on the posterior wall of the rectum. Surgical removal under
      general anesthesia involved polyp and its pedicle. Dimensions of the extirpation
      material were 1.5 x 1.0 x 0.8 cm. Histopathological examination and
      immunohistochemistry study of the polyp revealed a high-grade B-cell lymphoma
      (Burkitt lymphoma). These studies also showed lymphoma cells on the surgical
      border. The patient was referred to pediatric oncology center for chemotherapy.
      Primary rectal lymphoma in childhood is extremely rare; therefore, the
      possibility of malignancy in rectal polyps should be considered in the pediatric
      patients.

PMID- 18810466
TI  - The change pattern of SP and NO in the portal vein during the RAIR.
AB  - PURPOSE: To investigate the change pattern of substance P (SP) and nitric oxide
      (NO) in the portal vein during the recto-anal inhibitory reflex (RAIR), and its
      physiological significance; the influence of external splanchnic nerve (ESN) of
      rectum and anus to the RAIR. MATERIALS AND METHODS: Seventy-six rats divided into
      five groups according to the distance of Foley's tube in the rectum and whether
      or not to cut off ESN supply to the rectum and anal canal, to measure the values
      of SP and NO in the portal vein during the RAIR. RESULTS: The stimulus in rectum
      can cause change of SP and NO in portal vein. The greatest increase of SP is at
      the 6-cm group. The 6-cm group with total ESN supply had significant difference
      compared with the 4-cm group before and after the ESN supply and control group
      were cut (P<0.01). After cutting-off ESN, the increase of SP in the portal vein
      reduced significantly when compared with the normal ESN supply at the 6-cm group
      (P<0.05). The greatest change of NO is at the 4-cm group with total ESN. There
      were significant differences among the 4- and 6-cm groups and control group.
      After cutting off ESN, the increase of NO was lower than with the intact ESN.
      There were still differences between the 4- and 6-cm groups and control
      group(P<0.05). CONCLUSION: The stimulations at different points of the rectum
      cause different SP and NO change in the portal vein. This may be the explanation
      why the stimulation on the different points on the rectum induces different
      change pattern of RAIR from the neurotransmitters point. The ESN supplies of the
      rectum and anal canal have an influence on the change of SP and NO in the portal
      vein during RAIR.

PMID- 18810467
TI  - [Possibilities of wrist arthroscopy. Even for patients with arthritis?].
AB  - The wrist is the most commonly involved joint in rheumatoid arthritis (RA).
      Because it becomes involved early in the disease course and because this
      involvement rapidly progresses, early and adequate treatment is necessary to
      prevent disease progression. Arthroscopic synovectomy is recommended for pain
      relief and functional recovery in early-stage RA and is also helpful in advanced
      RA. The technique is complicated, and the learning curve is steep, but its
      efficiency is high. Arthroscopic synovectomy of the wrist reduces pain and
      improves function in most cases. It also improves motion, which is an advantage
      to the open procedure, and patient acceptance of this procedure is high.
      Nevertheless, arthroscopic synovectomy may delay the need for complex surgery,
      such as wrist arthrodesis or total wrist arthroplasty in selected cases.

PMID- 18810468
TI  - Abstracts of the 36th Congress of the German Society of Rheumatology. September
      24-27, 2008. Berlin, Germany.

PMID- 18810470
TI  - Thiazin red as a neuropathological tool for the rapid diagnosis of Alzheimer's
      disease in tissue imprints.
AB  - In recent years, we have used a variety of tau immunological markers combined
      with the dye thiazin red (TR), an accurate marker to differentiate the fibrillar
      from the nonfibrillar state of both amyloid-beta and tau in Alzheimer's disease
      (AD). In this study, we used TR as a potential diagnostic marker of AD in frozen
      thawed (F-T) brain tissue and imprint cytology. Control experiments included the
      use of Thioflavin-S staining, fixed tissue, and some double-labeled material with
      TR and selected tau markers, including AT100, MC1, Alz-50, TG-3, Tau-C3, and
      S396. Our results indicate that TR retains its strong affinity for both tangles
      and plaques in unfixed F-T tissue and imprint cytology. This information provides
      a potential use of TR as an accurate diagnostic tool for the rapid postmortem
      diagnosis of AD neuropathology. This study shows the advantages of TR on cytology
      mainly because tools for the fast postmortem diagnosis of AD are practically
      nonexistent. In addition, we observed Tau-C3 immunoreactivity in extracellular
      tangles, suggesting that the Tau-C3 epitope is characteristically stable.
      Moreover, this study demonstrates that chemical fixation is not necessarily
      required for tau immunoreactivity on histological sections.

PMID- 18810471
TI  - Increased PrPC expression correlates with endoglin (CD105) positive microvessels
      in advanced carotid lesions.
AB  - Normal cellular prion protein (PrP(C)) has multiple functions but its role in the
      development of atherosclerosis has not been studied. Our pilot microarray data
      showed increased expression of PrP(C) in tissue samples of complicated carotid
      lesions. Therefore in this study, we aimed to investigate its localisation within
      atherosclerotic arteries and its concentration in patient plasma. PrP(C)
      expression was examined using an enzyme immunometric assay (EIA) in plasma from
      patients undergoing endarterectomy. Carotid specimens and control vascular
      transplants were studied for PrP(C) and CD105 (endoglin, a marker of active
      vessels) expression by immunohistochemistry and real-time PCR. Patients with
      carotid disease had higher levels of plasma PrP(C) than the control group [4.35
      ng/ml (n = 22; 3.1-5.3) vs. 1.95 ng/ml (n = 21; 1.1-2.5), P < 0.001].
      Furthermore, CD105-positive plaques had higher PrP(C) expression which
      colocalized with CD105 in neovessels. There was a significant correlation between
      mRNA expression of PrP(C) and CD105 in tested plaques (P < 0.001; r = 0.7)
      supporting our immunohistochemical findings. We conclude that PrP(C) is expressed
      in carotid specimens and may be associated with neovessel growth or survival in
      these plaques. Our results suggest a role for PrP(C) in modulating neovessel
      formation in complicated plaques.

PMID- 18810473
TI  - Primary septic arthritis of the acromio-clavicular joint: case report and review
      of literature.
AB  - Primary septic arthritis of the Acromio clavicular joint is an uncommon disorder
      and is rarely seen even in an immunocompromised individual. We report a case of
      primary septic arthritis of the acromio-clavicular (A-C) joint caused by
      Staphylococcus aureus without any predisposing factors. The patient was admitted
      with left shoulder pain, restricted movements and fever. Laboratory parameters
      showed high C-reactive protein, raised erythrocyte sedimentation rate and
      leucocytosis. Blood cultures were positive for Staphylococcus-aureus. Magnetic
      resonance imaging (MRI) using Gadolinium enhancement revealed marked effusion in
      the A-C joint. Aspiration from the A-C joint revealed a heavy growth of
      Staphylococcus-aureus. The patient was successfully treated with 8 weeks of
      appropriate antibiotics with complete resolution of infection and return to full
      function.

PMID- 18810472
TI  - Surgical treatment for local control of extremity and trunk desmoid tumors.
AB  - INTRODUCTION: Surgical treatment has been the mainstay for extremity and trunk
      desmoid tumors with a negative surgical margin. However, even when resection with
      a wide surgical margin is achieved, the local recurrence rate remains high. The
      purpose of this study was to analyze the clinical outcome of patients with
      extremity and trunk desmoid tumors after surgical treatment and to determine the
      factors influencing local recurrence. MATERIALS AND METHODS: Between January 1991
      and December 2003, 30 of 58 patients with desmoid tumors referred to our
      institutions and surgically treated and followed up for more than 2 years were
      selected for this study. Patient age, gender, tumor size, location, status of
      disease (primary or recurrent), and surgical margins were analyzed as possible
      risk factors for recurrence. RESULTS: Sixteen (53%) of the 30 patients had a
      local recurrence. Eight of the 19 patients (42.1%) with a negative surgical
      margin experienced a recurrence. Younger age (<30 years) was a significant risk
      factor for local recurrence (P < 0.05). Tumor size, surgical margin and previous
      surgical history were not associated with local recurrence. Younger age and
      female gender had a propensity for local recurrence, suggesting that the
      biological behavior of desmoid tumor may depend on the status of the disease at
      presentation. CONCLUSIONS: These results suggest that radical surgical treatment
      causing severe functional impairment should be avoided in selected cases on the
      basis of patient characteristics, and that other novel therapeutic tools may be
      necessary for patients in whom a higher risk of local recurrence is assumed or
      severe complications after surgical treatment are predicted.

PMID- 18810474
TI  - The types of talar articular facets and morphometric measurements of the human
      calcaneus bone on Turkish race.
AB  - INTRODUCTION: There are three facets over upper side of talocalcaneal joint:
      anterior talar facet, middle and posterior. Three types of calcaneus that have
      distinct talar facets were defined as types A, B and C. MATERIALS AND METHODS: A
      total of 221 calcanei (98 right, 123 left), with unknown gender, were dried and
      evaluated. RESULTS: In our study type B calcaneus (58%) was defined as the most
      common type, and type A calcaneus (39.3%) as the second most common type. By
      using facet joint differences and bone measurement, we tried to define calcaneus
      bone. DISCUSSION: In many diseases of foot, such as the talocalcaneal artritis
      and coalition, intraarticular fractures and congenital dysmorphology, flatfood,
      valgus deformities, the size and shape of the bones, the relationships of the
      talus and calcaneus with each other and other bones of the foot must be
      considered for the internal and external fixation and surgical procedures. Type B
      calcaneus was defined as the most comman type in Turkish race and these results
      correlate with the ones which were performed on bones of American, Indian and
      African people, and it was uncorrelated with the results of the researches
      performed in Europe.

PMID- 18810475
TI  - Superficial fascial system repair: an abdominoplasty technique to reduce local
      complications after caesarean delivery.
AB  - Abdominal incision complications are a major source of morbidity after caesarean
      delivery. Repair of the superficial fascial system may avert local complications
      after caesarean delivery by minimising tension to the skin and increasing the
      initial biomechanical strength of wound which has the potential to decrease early
      wound dehiscence and as a by-product correct suprapubic bulging.

PMID- 18810476
TI  - Pregnancy spacing among women delaying initiation of childbearing.
AB  - INTRODUCTION: An increasing proportion of women in the US and other countries
      delay initiation of childbearing until their thirties. Little is known about
      their subsequent pregnancies, particularly with regard to pregnancy spacing.
      OBJECTIVES: To determine interpregnancy interval (IPI) patterns, factors
      associated with IPI among women delaying initiation of childbearing until their
      thirties, and ascertain if delay in initiation of childbearing is associated with
      increased likelihood for short interpregnancy interval of less than 6 months.
      METHODS: A retrospective cohort study was performed using the Missouri maternal
      linked file for 1978-1997, inclusive. Analysis was limited to mothers aged 20-50
      years at first pregnancy, having a first and second pregnancy during the study
      period; the sample size included 242,559 mother-infant pairs. Analysis strategies
      included stratified analysis, and multivariable logistic regression.
      Interpregnancy interval was main outcome variable, and was grouped in seven
      categories: 0-5, 6-11, 12-17, 18-23, 24-59, 60-119, >or=120 months. RESULTS: The
      mean interpregnancy interval was significantly shorter for women delaying start
      of childbearing (>or=30 years) compared to 20-29 year olds. Observed intervals
      are 31 (+/-24) months for mothers aged 20-29 years, 25 (+/-17) months for mothers
      aged 30-34 years, 21 (+/- 14) for 35-39 year olds, and 19 (+/-16) for 40-50 year
      olds (P < 0.0001). A significant trend for shorter intervals was noted as
      maternal age at first pregnancy increased (P < 0.0001). Factors associated with
      interpregnancy interval for women delaying initiation of childbearing included
      adverse outcome in preceding pregnancy, and low educational status. Mothers aged
      35 and above at first pregnancy had increased odds for a second pregnancy
      following short IPI <6 months; (35-39 years OR = 1.26 95% CI 1.11-1.44; 40-50 OR
      = 1.91 95% CI 1.13-3.24). Mothers aged 30-34 years have lower odds for short IPI
      (OR = 0.93 95% CI 0.87-0.99). CONCLUSION: First time mothers aged 35 and above
      have higher odds of having a second pregnancy shortly after their first
      pregnancy. Given the increasing number of first time mothers aged 35 and above,
      these findings are of relevance for preconception counseling for this unique
      population of women.

PMID- 18810477
TI  - Correlations between posturographic findings and symptoms in subjects with
      fractures of the condylar head of the mandible.
AB  - Our study examined the posture of 15 patients who had sustained a simple
      unilateral or bilateral fracture of the condylar head of the mandible as a result
      of sports or traffic accidents. Following preliminary testing of vestibular
      function, the patients underwent balance testing: Romberg test with eyes closed
      (EC), Romberg EC and bite test (ECBT), EC and head retroflexed (ECR). The study
      parameters were: surface (S) of the statokinesigram, stomatognathic influence
      index related to S (SSI), and postural oscillations on the frontal plane (X). In
      keeping with the literature, we felt that the following pattern in static balance
      suggested a posture destabilised by the stomatognathic system: SSI values of less
      than 60, reduction of S in the transition from EC to ECR, pathological increase
      of postural oscillations on the X plane. The study was completed by obtaining a
      list of new symptoms reported by the patients (altered bite, fullness, tinnitus,
      pain, loss of balance). The most significant patterns were observed in patients
      with vestibular dysfunctions and neck pain. It seems that a fracture of the
      condylar head can affect postural behaviour, although proprioceptive changes
      alone are not enough to cause true loss of balance and there must be concomitant
      vestibular dysfunction. The stabilometric pattern is not conditioned by the
      extent of the trauma or the related treatment. In terms of proprioceptive
      elements, the presence of muscle pain seems to point to cervical muscle tension
      as the main culprit in the onset of posttraumatic instability.

PMID- 18810478
TI  - Effect of diagnostic occlusion in acquired trochlear nerve palsy.
AB  - BACKGROUND: Monocular occlusion eliminates the stimulus for fusional vergence.
      Diagnostic occlusion may therefore be helpful in isolating the genuine profile of
      the fundamental ocular motility disorder, which may be an important finding
      regarding both differential diagnosis of strabismus and dosage of surgery. We
      investigated the effect of diagnostic occlusion on the motility pattern of
      acquired trochlear nerve palsy. PATIENTS AND METHODS: Forty-eight patients aged
      between 6 and 78 years (median 49 years) with unilateral trochlear nerve palsy
      were first examined without patching, and then after 3 days of diagnostic
      occlusion. The onset of palsy was 1-35 years before (median 2 years). Squint
      angles localized with a dark red glass in front of the non-paretic eye were
      measured at a distance of 2.5 m, using the Harms tangent screen. Vertical and
      cyclotorsional angles in primary position (PP), 25 degrees abduction of the non
      paretic eye (adduction of the paretic eye), and 25 degrees downgaze were
      measured. RESULTS: The relation between hyperdeviation of the paretic eye and
      excyclodeviation (medians of the angles in degrees, ranges in brackets) before
      and after diagnostic occlusion was 5/5 and 4/6 (0;14/-1;10 and 0;19/2;13) in PP.
      In contralateral gaze, the relation was 8/5 and 8/6 (0;21/0;10 and 1;24/1;15),
      and in downgaze, 10/7 and 8/8 (0;21/1;14 and 0;23/3;18). The increase in
      excyclodeviation, though statistically significant (in PP, p = 0.0002) was small,
      with a median of 1 degree and large variability. The decrease in hyperdeviation
      was statistically significant in downgaze. The head-tilt phenomenon remained
      unchanged. CONCLUSIONS: In patients with trochlear nerve palsy, diagnostic
      occlusion regularly causes an increase in excyclodeviation. In 25% of patients,
      this increase exceeds 3 degrees. The more variable change in vertical deviation,
      and the lack in change in the head-tilt phenomenon, can be explained by the fact
      that central gain-modulation causing an increase in both vertical deviation and
      the head-tilt phenomenon is not reversible within the relatively short time of 3
      days. Diagnostic occlusion can eliminate compensatory innervation and may thereby
      release the genuine motility pattern, but the occlusion can also induce
      artificial squint angles.

PMID- 18810479
TI  - Deposit of glass fragments during femtosecond laser penetrating keratoplasty.
AB  - BACKGROUND: To evaluate femtosecond laser interaction with the applanation lens
      during pre-programmed penetrating keratoplasty corneal cuts. METHODS: Three
      different-shaped penetrating keratoplasty dissections were performed on edematous
      corneas from bank eyes using a clinical femtosecond laser system (Intralase FS60)
      with energies higher than 2 microJ, and the "depth into glass" parameter at 50
      microm, which is defined as the length over which the laser interacts with the
      glass of the applanation cone in contact with the cornea. Additional full
      thickness corneal incisions were obtained with an experimental laser source with
      technical characteristics similar to the clinical laser. Following cutting,
      tissue sections were examined by optical microscopy (OM), transmission electron
      microscopy (TEM), and electron energy loss spectroscopy (EELS). After the
      procedure, the cones were examined by optical and scanning electron microscopy
      (SEM). A control was obtained by repeating the procedures and stopping the laser
      at the cornea-lens interface. RESULTS: OM and TEM analysis of the tissue showed
      the presence of solid particles of a maximum dimension of 1.5 mum on the
      epithelium and the anterior stroma, regardless of the laser system used to cut.
      The EELS technique revealed their composition as silicon dioxide. We believe that
      the fragments originate from the applanation cone, which is machined by the laser
      interacting with the glass in contact with cornea. This is consistent with the
      structures observed on the lens by OM and SEM. Radial and circumferential tracks
      on the surface of the lens are visible, corresponding to the laser path in
      penetrating keratoplasty protocols. No particles were found in the control
      samples. CONCLUSIONS: When performing penetrating keratoplasty corneal cuts by
      infra-red femtosecond laser, the applanation lens in contact with the cornea is
      machined by the laser depending on the system parameters. As a consequence,
      microscopic glass fragments are created, which may remain in the tissue. This
      unwanted effect can be avoided by stopping the procedure at the lens-cornea
      interface.

PMID- 18810480
TI  - Improved reproducibility of retinal nerve fiber layer thickness measurements with
      the repeat-scan protocol using the Stratus OCT in normal and glaucomatous eyes.
AB  - BACKGROUND: Optical coherence tomography has become within the last years an
      established imaging technique with many applications in ophthalmology, and an
      important tool which contributes to earlier and more accurate diagnosis of
      glaucoma. As a consequence, detection sensitivity is highly valued. The aim of
      this study was to assess the reproducibility of peripapillary retinal nerve fiber
      layer (RNFL) thickness measurements by the Stratus Optical Coherence Tomograph
      (OCT) using the Fast- and Repeat-scan protocols in normal and glaucomatous eyes.
      METHODS: In the clinical setting, RNFL thickness measurements were obtained from
      a control group of 40 subjects, consisting of 20 normal volunteers and 20
      glaucoma patients. One eye was randomly chosen from each subject, and underwent
      five RNFL thickness measurements with the Fast- and five with the Repeat-scan
      protocol, which was also based on the Fast-scan mode. Reproducibility was
      assessed by the intraclass correlation coefficient (ICC) and the coefficient of
      variation (CV) for the overall mean RNFL thickness and for each quadrant and
      clock hour of the peripapillary area. RESULTS: The Repeat-scan protocol yielded
      higher ICC and lower CV values in all quadrants and clock hours of the
      peripapillary area, both in normal and glaucomatous subjects. The difference in
      CV values between Fast- and Repeat-scan protocol measurements reached statistical
      significance in the temporal quadrant (P = 0.021) and in clock hour sectors 8, 9
      and 12 (P = 0.022, 0.017 and 0.03 respectively). ICC (and CV) for the temporal-,
      superior-, nasal- and inferior-quadrant RNFL thickness was: for the Fast-scan
      protocol, 0.913 (7.4%), 0.925 (6.97%), 0.828 (10.31%), 0.964 (4.89%)
      respectively; and for the Repeat-scan protocol, 0.965 (5.08%), 0.958 (5.26%),
      0.906 (8.12%) 0.968 (4.6%) respectively. CONCLUSIONS: Reproducibility of RNFL
      thickness measurements with the Fast- and Repeat-scan protocols by the Stratus
      OCT is proved to be very high both in normal and glaucomatous subjects. The
      Repeat-scan protocol shows higher ICC and lower CV values, statistically
      significant especially on the temporal side of the peripapillary area, which may
      indicate a higher reproducibility and greater agreement of measurements. These
      findings support the fact that the Repeat-scan protocol might be considered as a
      more precise method for evaluation of RNFL thickness.

PMID- 18810481
TI  - Selecting highly sensitive non-obese diabetic mice for improving the study of
      Sjogren's syndrome.
AB  - BACKGROUND: Non-obese diabetic (NOD) mice are a commonly used murine model for
      the study of Sjogren's syndrome. However, variations in susceptibility to the
      disease among the mice has often yielded less stable results. Based on the
      correlation between the pathological changes and the tear tests, we attempt to
      establish a simple screening procedure to assure the validity of experimental
      results by excluding those mice with poor susceptibility to dry eyes. METHODS:
      Seventy male NOD mice were recruited. The tear film break-up test (BUT) and the
      phenol red cotton thread test (CTT) were implemented while the mice were under
      anesthesia. The mice were divided into four groups (grades 1 to 4) based on their
      BUT readings, and four similar groups based on CTT measurements. Tear samples in
      each grade were collected for IL-1beta detection with ELISA. The lacrimal glands
      and conjunctiva of the mice were used to detect the levels of leucocyte common
      antigen (LCA). LCA-Positive staining was considered as the "gold standard" in the
      receiver operating characteristic curve (ROC curve) analysis. C57BL/6 mice were
      used as wild-type controls. RESULTS: There were 13 (18.57%), 43 (61.43%), 10
      (14.29%) and 4 (5.71%) mice in grades 1, 2, 3 and 4 by BUT test, and 34 (48.57%),
      15 (21.43%), 14 (20.00%) and 7 (10.00%) in grades 1, 2, 3 and 4 by CTT test
      respectively. Fifty-one out of the 70 mice (72.86%) were detected LCA-positive,
      and they were mainly in grades 1 and 2 of both the BUT and CCT grading systems.
      ELISA showed significant variances of IL-beta levels among the four groups (p <
      0.01), with much lower IL-beta levels in group 3 and 4 when both BUT and CTT were
      used for grouping. The tear IL-beta level in the wild-type mice was similar to
      those of the grade 4 mice, using either BUT or CTT for grouping. The ROC curve
      analysis provided optimal cutting lines, which were 2 seconds in BUT readings and
      4 mm/min in CTT measurements respectively. CONCLUSION: BUT and CTT tests are
      useful methods in screening high susceptible NOD mice. Cutting lines at BUT < or
      = 2 seconds and CTT < or = 4 mm/min provide a good balance between the assurance
      of susceptibility and the maximization of use of NOD mice for the study of
      Sjogren's syndrome.

PMID- 18810482
TI  - Widefield fluorescence microscopy with extended resolution.
AB  - Widefield fluorescence microscopy is seeing dramatic improvements in resolution,
      reaching today 100 nm in all three dimensions. This gain in resolution is
      achieved by dispensing with uniform Kohler illumination. Instead, non-uniform
      excitation light patterns with sinusoidal intensity variations in one, two, or
      three dimensions are applied combined with powerful image reconstruction
      techniques. Taking advantage of non-linear fluorophore response to the excitation
      field, the resolution can be further improved down to several 10 nm. In this
      review article, we describe the image formation in the microscope and
      computational reconstruction of the high-resolution dataset when exciting the
      specimen with a harmonic light pattern conveniently generated by interfering
      laser beams forming standing waves. We will also discuss extensions to total
      internal reflection microscopy, non-linear microscopy, and three-dimensional
      imaging.

PMID- 18810484
TI  - The relationship between malignant mesothelioma and an asbestos cement plant
      environmental risk: a spatial case-control study in the city of Bari (Italy).
AB  - OBJECTIVES: To estimate the mesothelioma risk and environmental asbestos exposure
      (EAE) due to an asbestos-cement plant. METHODS: A spatial case-control study
      including 48 malignant mesothelioma (MM) cases occurred in the period 1993-2003
      selected from the regional mesothelioma register (RMR) and 273 controls. The
      disease risk was estimated by means of a logistic-regression model, in which the
      probability of disease-occurrence is expressed as a function of the classes of
      distances. A non-parametric method was applied to estimate the full relative risk
      surface. RESULTS: Significant MM odds ratio of 5.29 (95 CI: 1.18-23.74) was found
      for people living within a range up to 500 m centered on the plant. The non
      parametric estimation of relative risk surface unveiled a marked peak near the
      plant not paralleled by the spatial distribution of controls. CONCLUSION:
      Evidence of an association between mesothelioma risk and EAE is highlighted. The
      role played by the RMR in increasing the public health local authorities
      awareness is stressed.

PMID- 18810483
TI  - Distribution of P2X(3) receptor immunoreactivity in myenteric ganglia of the
      mouse esophagus.
AB  - Intraganglionic laminar endings (IGLEs) represent the major vagal afferent
      terminals throughout the gut. Electrophysiological experiments revealed a
      modulatory role of ATP in the IGLE-mechanotransduction process and the P2X(2)
      receptor has been described in IGLEs of mouse, rat and guinea pig. Another
      purinoceptor, the P2X(3)-receptor, was found in IGLEs of the rat esophagus. These
      findings prompted us to investigate occurrence and distribution of the P2X(3)
      receptor in the mouse esophagus. Using multichannel immunofluorescence and
      confocal microscopy, P2X(3)-immunoreactivity (-iry) was found colocalized with
      the vesicular glutamate transporter 2 (VGLUT2), a specific marker for IGLEs, on
      average in three-fourths of esophageal IGLEs. The distribution of P2X(3)
      immunoreactive (-ir) IGLEs was similar to that of P2X(2)-iry and showed
      increasing numbers towards the abdominal esophagus. P2X(3)/P2X(2)-colocalization
      within IGLEs suggested the occurrence of heteromeric P2X(2/3) receptors. In
      contrast to the rat, where only a few P2X(3)-ir perikarya were described, P2X(3)
      stained perikarya in ~80% of myenteric ganglia in the mouse. Detailed analysis
      revealed P2X(3)-iry in subpopulations of nitrergic (nNOS) and cholinergic (ChAT)
      myenteric neurons and ganglionic neuropil of the mouse esophagus. We conclude
      that ATP might act as a neuromodulator in IGLEs via a (P2X(2))-P2X(3) receptor
      mediated pathway especially in the abdominal portion of the mouse esophagus.

PMID- 18810485
TI  - Matrix metallopeptidase 2 activity in tendon regions: effects of mechanical
      loading exercise associated to anabolic-androgenic steroids.
AB  - Matrix metallopeptidases (MMPs) are responsible for degradation of the
      extracellular matrix components and tissue remodeling. To achieve a better
      understanding of AAS effects in rat tendon, MMP-2 activity in the proximal and
      distal regions of the calcanear tendon (CT) and proximal, intermediate and distal
      region of superficial (SFT) and deep flexor tendons (DFT) after mechanical load
      exercise associated with AAS was investigated. Animals were grouped into four
      groups: sedentary animals (S); sedentary animals with ASS supplementation (S +
      A); trained animals (T) and trained animals with AAS supplementation (T + A).
      Analysis of MMP activity in tendon extracts was done by gelatin zymography. Both
      proximal and distal regions of the calcanear tendon showed the lowest MMP-2
      concentration and the highest proportion in MMP-2 active form. The intermediate
      region of the SFT differed (P < 0.01) from the proximal and distal regions with
      higher % of active MMP-2 in the sedentary group. The proportion of active MMP-2
      decreased in the proximal region of the CT. AAS treatment strongly decreased both
      MMP-2 concentration and active form in the three regions of the SFT and on the
      proximal region of the CT, but not on the DFT. The differences in the response to
      exercise and AAS treatment are a result of distinct metabolism and recruitment of
      these tendon regions in the exercise program employed in this study.

PMID- 18810486
TI  - Enhanced signal detectability in comodulated noise introduced by compression.
AB  - Many examples of natural noise show common amplitude modulations at different
      frequency regions. This kind of noise has been termed comodulated noise and is
      widely examined in hearing research, where an enhanced detectability of pure
      tones and narrow noise bands in comodulated noise compared to unmodulated noise
      is well known as the CMR or CDD effects, respectively. Here it is shown that only
      one signal processing step, a compressive nonlinearity motivated by the
      peripheral auditory system, is sufficient to explain a considerable contribution
      to these effects. Using an analytical approach, the influence of compression on
      the detectability of periodic and narrow band signals in the presence of
      unmodulated and comodulated noise is investigated. This theoretical treatment
      allows for identifying the mechanism leading to improved signal detection. The
      compressive nonlinearity constitutes an adaptive gain which selectively boosts a
      stimulus during time spans of inherently increased signal-to-noise ratio and
      attenuates it during time spans dominated by noise. On average, these time spans
      are more pronounced in stimuli with comodulated noise than with unmodulated
      noise, thus giving rise to the observed CMR and CDD effects.

PMID- 18810487
TI  - The microgenesis of action-effect binding.
AB  - Ideomotor theories of human action control assume that performing a movement
      leads to the automatic integration of the underlying motor pattern with codes of
      its perceptual consequences. We studied the microgenesis of action-effect
      integration by varying the mapping of action effects upon actions from trial to
      trial. Experiments 1 and 2 showed that perceiving a tone repetition
      systematically affects one's tendency to carry out the response that produced
      that tone in the previous trial, suggesting that even the unintentional
      production of a stimulus creates a temporary binding of that stimulus with the
      action that brought it about. Experiments 3 and 4 extended this finding in
      suggesting that the integration and/or retrieval of action effects is modulated
      by attentional factors: Ongoing performance is more impacted by action effects if
      they are salient or match the current attentional set.

PMID- 18810488
TI  - Epigenetic deregulation of the human Oct4 promoter in mouse cells.
AB  - To examine whether the epigenetic status of the human Oct4 promoter is similarly
      regulated in mouse cells, we engineered a human bacterial artificial chromosome
      to express green fluorescent protein under the control of the hOct4 promoter and
      stably integrated it into mouse embryonic stem cells (mESCs), NIH3T3, and 293T
      cells. The hOct4 promoter is unmethylated in mESCs and it undergoes methylation
      during retinoic acid-induced differentiation. However, the hOct4 promoter is
      demethylated in NIH3T3 cells even though it is fully methylated in 293T cells.
      Methylation status of the hOct4 promoter is associated with green fluorescent
      protein expression at transcription level. Our findings indicate that the hOct4
      promoter is differently regulated in mouse cells.

PMID- 18810489
TI  - Expression pattern of annelid Zic in embryonic development of the oligochaete
      Tubifex tubifex.
AB  - Embryonic expression of a Zic homologue (Ttu-Zic) was examined in the oligochaete
      annelid Tubifex tubifex. The body plan of T. tubifex is characterized by obvious
      segmentation in the ectoderm and mesoderm. Ttu-Zic expression is detected in the
      mesodermal germ band and a subset of micromere descendants. Ttu-Zic is
      transiently expressed in primary m-blast cells (i.e., founder cells of mesodermal
      segments) as early as the time of their birth from M teloblasts. During its
      development, each mesodermal segment experiences two additional phases of Ttu-Zic
      expression. Ttu-Zic expression in micromere descendants is seen on the anterior
      surfaces of embryos undergoing teloblastogenesis; subsequently, these cells
      proliferate to form bilateral clusters, which then become internalized. Finally,
      clusters of Ttu-Zic-expressing cells are found in the center of the prostomium,
      corresponding to the cerebral ganglion. The Ttu-Zic expression profile in the
      early embryogenesis of T. tubifex may be homologous to those of evolutionarily
      distant animals.

PMID- 18810490
TI  - The bradykinin B2 receptor in the early immune response against Listeria
      infection.
AB  - The endogenous danger signal bradykinin was recently found implicated in the
      development of immunity against parasites via dendritic cells. We here report an
      essential role of the B(2) (B(2)R) bradykinin receptor in the early immune
      response against Listeria infection. Mice deficient in B(2)R (B(2)R(-/-) mice)
      were shown to suffer from increased hepatic bacterial burden and concomitant
      dramatic weight loss during infection with Listeria monocytogenes. Levels of
      cytokines known to play a pivotal role in the early phase immune response against
      L. monocytogenes, IL-12p70 and IFN-gamma, were reduced in B(2)R(-/-) mice. To
      extend these findings to the human system, we show that bradykinin potentiates
      the production of IL-12p70 in human monocyte-derived dendritic cells. Thus, we
      show that bradykinin and the B(2)R play a role in early innate immune functions
      during bacterial infection.

PMID- 18810491
TI  - Inhibition of HBV infection by bovine lactoferrin and iron-, zinc-saturated
      lactoferrin.
AB  - In this study, we investigated the effect of bovine lactoferrin (BLf),
      lactoferrin hydrolysate, or iron-, zinc-saturated lactoferrin on hepatitis B
      virus (HBV)-infected HepG2 cells. Fluorescent quantitative polymerase chain
      reaction (FQ-PCR) was used to quantify HBV-DNA copies. BLf, iron- or zinc
      saturated lactoferrin significantly inhibited the amplification of HBV-DNA in a
      dose-dependent manner in HBV-infected HepG2 cells. However, the inhibitive effect
      of lactoferrin hydrolysate on HBV-DNA copies was insignificant. These findings
      suggest that BLf inhibits the function of HBV by integrated structure. In
      conclusion, BLf, iron- or zinc-saturated BLf is one of the candidates for anti
      HBV reagents in treatment of patients with hepatitis.

PMID- 18810492
TI  - Antiparasitic activity of biochanin A, an isolated isoflavone from fruits of
      Cassia fistula (Leguminosae).
AB  - The fractionation through bioguided antileishmanial activity of the
      dichloromethane extract of Cassia fistula fruits (Leguminosae) led to the
      isolation of the active isoflavone biochanin A, identified by spectroscopic
      methods. This compound showed 50% effective concentration (EC(50)) value of 18.96
      microg/mL against promastigotes of Leishmania (L.) chagasi. The cytotoxicity of
      this substance against peritoneal macrophages resulted in an EC(50) value of
      42.58 microg/mL. Additionally, biochanin A presented an anti-Trypanosoma-cruzi
      activity, resulting in an EC(50) value of 18.32 microg/mL and a 2.4-fold more
      effectiveness than benznidazole. These results contribute with novel
      antiprotozoal compounds for future drug design studies.

PMID- 18810493
TI  - Setaria tundra microfilariae in reindeer and other cervids in Finland.
AB  - Harmful parasites of the wild northern boreal mammals are still surprisingly
      poorly studied. In 2003-2006, a peritonitis outbreak caused by the filarioid
      nematode, Setaria tundra, emerged in Finland's reindeer population. In order to
      gain knowledge about the basic biology, epidemiology, and transmission dynamics
      of this parasite, samples for S. tundra were collected from reindeer and other
      cervids during the follow-up period 2004-2006. Using morphology and molecular
      biology methods, we describe here S. tundra's first larval stage, microfilaria
      (smf), for the first time scientifically. The prevalence and densities of smf
      were higher in reindeer calves than in adults, overall prevalence being 42%. The
      overall smf prevalences for moose, wild forest reindeer and roe deer were 1.4
      1.8%, 23%, and 39%, respectively. The focus of microfilaremia moved north and
      settled down in the south simultaneously with the peritonitis outbreak. The peak
      microfilaremia occurred in the first summer after the infection, and smf
      disappeared from the blood after 2 years. Captive reindeer were smf positive over
      the year. The prepatent period of S. tundra was estimated to be about 4 months,
      and the life span at least 14 months. This parasite likely has an important
      impact on boreal ecosystems.

PMID- 18810494
TI  - Bioactivity of flavonoid compounds from Poncirus trifoliata L. (Family: Rutaceae)
      against the dengue vector, Aedes aegypti L. (Diptera: Culicidae).
AB  - The bioactivity of four flavonoid compounds, namely poncirin, rhoifolin, naringin
      and marmesin, from Poncirus trifoliata was studied against the Aedes aegypti.
      Larvicidal assays were conducted to evaluate the 24 h LC(50) and LC(90) values of
      the flavonoid compounds. The lethal concentration (LC(50) and LC(90)) values
      ranged from 0.082 to 0.122 mg/l and 0.152 to 0.223 mg/l, respectively. The result
      of ovicidal test suggests that the ovicidal activity of the flavonoid compounds
      was influenced by the concentration of flavonoid compounds and age of the eggs.
      The result of oviposition test showed that the four flavonoid compounds exhibited
      oviposition-deterrent activity against gravid female mosquitoes. Oviposition
      decreased with an increase in concentration of flavonoid compounds. A laboratory
      test was carried out to evaluate protection period and percentage of repellency
      of four compounds diluted in ethanol (10 mg/l). The compound rhoifolin provided
      maximum 365.0 +/- 12.0 min protection and also 100.0% +/- 0.0 repellency against
      mosquito bite followed by poncirin, marmesin and naringin. None of the 25
      volunteers of either sex exposed to 10% (w/v) flavonoid compounds (4-h patch
      test) showed a positive skin irritant reaction. All of the tested compounds
      proved to have various activities against different life stages of A. aegypti.
      Therefore, flavonoid compounds from P. trifoliata can be a potential candidate
      for use in the development of commercial mosquitocidal products that may be an
      alternative to conventional synthetic chemicals, particularly in integrated
      vector control applications.

PMID- 18810495
TI  - KT/HAK/KUP potassium transporters gene family and their whole-life cycle
      expression profile in rice (Oryza sativa).
AB  - KT/HAK/KUP potassium transporter protein-encoding genes constitute a large family
      in the plant kingdom. The KT/HAK/KUP family is important for various
      physiological processes of plant life. In this study, we identified 27 potential
      KT/HAK/KUP family genes in rice (Oryza sativa) by database searching. Analysis of
      these KT/HAK/KUP family members identified three conserved motifs with unknown
      functions, and 11-15 trans-membrane segments, most of which are conserved. A
      total of 144 putative cis-elements were found in the 2 kb upstream region of
      these genes, of which a Ca2+-responsive cis-element, two light-responsive cis
      elements, and a circadian-regulated cis-element were identified in the majority
      of the members, suggesting regulation of these genes by these signals. A
      comprehensive expression analysis of these genes was performed using data from
      microarrays hybridized with RNA samples of 27 tissues covering the entire life
      cycle from three rice genotypes, Minghui 63, Zhenshan 97, and Shanyou 63. We
      identified preferential expression of two OsHAK genes in stamen at 1 day before
      flowering compared with all the other tissues. OsHAK genes were also found to be
      differentially upregulated or downregulated in rice seedlings subjected to
      treatments with three hormones. These results would be very useful for
      elucidating the roles of these genes in growth, development, and stress response
      of the rice plant.

PMID- 18810496
TI  - Association between Apolipoprotein E genotype and cerebral palsy is not confirmed
      in a Caucasian population.
AB  - Apolipoprotein E (APOE) plays a significant role in lipid metabolism and has been
      implicated in the growth and repair of injured neurons. Two small studies have
      suggested an association between APOE genotype and cerebral palsy. We
      investigated if APOE genotype is associated with an increased risk for cerebral
      palsy, influences the type of cerebral palsy or interacts with prenatal viral
      infection to influence risk of cerebral palsy. The population-based case-control
      study comprised newborn screening cards of 443 Caucasian patients with cerebral
      palsy and 883 Caucasian matched controls. APOE genotyping was performed on DNA
      extracted from dried blood spots. Allelic and genotypic frequencies did not
      differ between cases and controls and combined frequencies were 0.10 (epsilon2),
      0.76 (epsilon3), 0.14 (epsilon4), 0.03 (epsilon2/epsilon2), 0.10
      (epsilon2/epsilon3), 0.03 (epsilon2/epsilon4), 0.02 (epsilon4/epsilon4), 0.21
      (epsilon3/epsilon4), 0.61 (epsilon3/epsilon3). APOE genotype was correlated with
      cerebral palsy, type of cerebral palsy, gestation at birth and the presence of
      viral nucleic acids detected in previous work. Analysis by gestational age (all
      gestational ages, >/=37, 32-36 and <32 weeks) and type of cerebral palsy (all
      types, diplegia, hemiplegia and quadriplegia) showed no association between APOE
      genotype and cerebral palsy in this Caucasian population. An association between
      prenatal viral infection, APOE genotype and cerebral palsy was not demonstrated.
      These results did not confirm an association between APOE genotype, cerebral
      palsy, type of cerebral palsy and prenatal infection in a Caucasian population.
      Given the low frequency of APOE epsilon2 and some of the heterozygote and
      homozygote combinations in this study, a larger study is assessing this further.

PMID- 18810497
TI  - The clinical characteristics of Werner syndrome: molecular and biochemical
      diagnosis.
AB  - Werner syndrome (WS) is an adult onset segmental progeroid syndrome caused by
      mutations in the WRN gene. The WRN gene encodes a 180 kDa nuclear protein that
      possesses helicase and exonuclease activities. The absence of WRN protein leads
      to abnormalities in various DNA metabolic pathways such as DNA repair,
      replication and telomere maintenance. Individuals with WS generally develop
      normally until the third decade of life, when premature aging phenotypes and a
      series of age-related disorders begin to manifest. In Japan, where a founder
      effect has been described, the frequency of Werner heterozygotes appears to be as
      high as 1/180 in the general population. Due to the relatively non-specific
      nature of the symptoms and the lack of awareness of the condition, this disease
      may be under-diagnosed in other parts of the world. Genetic counseling of WS
      patients follows the path of other autosomal recessive disorders, with special
      attention needed for cancer surveillance in relatives. Molecular diagnosis of WS
      is made by nucleotide sequencing and, in some cases, protein analysis. It is also
      of potential interest to measure WRN activities in WS patients. More than 50
      different disease-causing mutations in the WRN gene have been identified in WS
      patients from all over the world. All but one of these cases has mutations that
      result in the premature termination of the protein. Here we describe the
      clinical, molecular and biochemical characteristics of WS for use by medical
      professionals in a health care setting. Additional information is available
      through the International Registry of WS (http://www.wernersyndrome.org).

PMID- 18810498
TI  - Crop size, plant aggregation, and microhabitat type affect fruit removal by birds
      from individual melastome plants in the Upper Amazon.
AB  - We studied the efficiency (proportion of the crop removed) and quantitative
      effectiveness (number of fruits removed) of dispersal of Miconia fosteri and M.
      serrulata (Melastomataceae) seeds by birds in lowland tropical wet forest of
      Ecuador. Specifically, we examined variation in fruit removal in order to reveal
      the spatial scale at which crop size influences seed dispersal outcome of
      individual plants, and to evaluate how the effect of crop size on plant dispersal
      success may be affected by conspecific fruit abundance and by the spatial
      distribution of frugivore abundance. We established two 9-ha plots in undisturbed
      terra-firme understory, where six manakin species (Pipridae) disperse most seeds
      of these two plant species. Mean levels of fruit removal were low for both
      species, with high variability among plants. In general, plants with larger crop
      sizes experienced greater efficiency and effectiveness of fruit removal than
      plants with smaller crops. Fruit removal, however, was also influenced by
      microhabitat, such as local topography and local neighborhood. Fruit-rich and
      disperser-rich patches overlapped spatially for M. fosteri but not M. serrulata,
      nonetheless fruit removal of M. serrulata was still much greater in fruit-rich
      patches. Fruit removal from individual plants did not decrease in patches with
      many fruiting conspecifics and, in fact, removal effectiveness was enhanced for
      M. fosteri with small crop sizes when such plants were in patches with more
      conspecifics. These results suggest that benefits of attracting dispersers to a
      patch balanced or outweighed the costs of competition for dispersers. Spatial
      pattern of fruit removal, a measure of plant fitness, depended on a complex
      interaction among plant traits, spatial patterns of plant distribution, and
      disperser behavior.

PMID- 18810499
TI  - Carbon balance of conifer seedlings at timberline: relative changes in uptake,
      storage, and utilization.
AB  - Low rates of growth for conifers at high elevations may relate to problems in
      acquiring or utilizing carbon. A traditional hypothesis for growth limits of
      trees at alpine treeline is that low photosynthesis (A) leads to insufficient
      supply of carbon for growth. Alternatively, the sink-limitation hypothesis
      questions the importance of low A, and suggests that trees at treeline have
      abundant carbon for growth as a result of greater decreases in carbon use
      [respiration (R) and growth] than A at higher elevations. Concentrations of
      carbon intermediates (e.g., nonstructural carbohydrates, NSC) have been used to
      support the sink-limitation hypothesis, with the assumption that NSC reflects the
      ratio of carbon source to sinks. Our objective was to determine elevation effects
      on carbon balance (whole-plant uptake, storage, and efflux of carbon) of tree
      seedlings during their critical establishment phase at timberline. Changes in A
      and R (of whole crowns), NSC (starches and simple sugars), and growth were
      measured in seedlings of a treeline (Abies lasiocarpa) and nontreeline species
      (Pseudotsuga menziesii). Seedlings were outplanted at the lower (2,450 m) and
      upper (3,000 m) edges of the timberline zone in the Rocky Mountains, USA. At the
      upper compared with lower elevation, both species had 10-20% less root and needle
      growth, 13-15% less A, 35-39% less R, and up to 50% greater NSC. A. lasiocarpa
      allocated more biomass to needles and had greater A but less NSC than P.
      menziesii. The greater effects of elevation on R compared with A led to a 1.3
      fold increase in A:R at the upper elevation, and a corresponding increase in
      starch (r2 = 0.42)-a pattern consistent with the predictions of the sink
      limitation hypothesis. Nevertheless, A and dry mass gain were positively
      correlated (r2 = 0.42), indicating that variation in photosynthesis was related
      to growth of seedlings at timberline.

PMID- 18810500
TI  - Fundamental limits to the accuracy of deuterium isotopes for identifying the
      spatial origin of migratory animals.
AB  - Deuterium isotope analyses have revolutionized the study of migratory
      connectivity because global gradients of deuterium in precipitation (deltaD(P))
      are expressed on a continental scale. Several authors have constructed
      continental scale base maps of deltaD(P) to provide a spatial reference for
      studying the movement patterns of migratory species and, although they are very
      useful, these maps present a static, 40-year average view of the landscape that
      ignores much underlying inter-annual variation. To more fully understand the
      consequences of this underlying variation, we analyzed the GNIP deuterium data,
      the source for all current deltaD(P) maps, to estimate the minimum separation in
      deltaD(P) (and latitude) necessary to conclude with a given level of confidence
      that distinct deltaD(P) values represent different geographic sites. Extending
      analyses of deltaD(P) successfully to deuterium in tissues of living organisms,
      e.g., feathers in migratory birds (deltaD(F)), is dependent on the existence of
      geographic separation of deltaD(P), where every geographic location has a
      distribution of values associated with temporal variability in deltaD(P).
      Analyses were conducted for three distinct geographic regions: North America,
      eastern North America (east of longitude 100 degrees W), and Argentina. At the
      80% confidence level, the minimum separation values were 12, 7, and 14 degrees of
      latitude (equivalent to 53, 31, and 32 per thousand) for North America, eastern
      North America, and Argentina, respectively. Hence, in eastern North America, for
      example, one may not be able to accurately assign individual samples to sites
      separated by less than about 7 degrees of latitude as the distributions of
      deltaD(P) were not distinct at latitudes <7 degrees apart. Moreover, two samples
      that differ by less than 31 per thousand cannot be confidently said to originate
      from different latitudes. These estimates of minimum separation for deltaD(P) do
      not include other known sources of variation in feather deuterium (deltaD(F)) and
      hence are a first order approximation that may be useful, in the absence of more
      specific information for the system of interest, for planning and interpreting
      the results of new stable isotope studies.

PMID- 18810501
TI  - Isotope signatures in winter moulted feathers predict malaria prevalence in a
      breeding avian host.
AB  - It is widely accepted that animal distribution and migration strategy might have
      co-evolved in relation to selection pressures exerted by parasites. Here, we
      first determined the prevalence and types of malaria blood parasites in a
      breeding population of great reed warblers Acrocephalus arundinaceus using PCR.
      Secondly, we tested for differences in individual feather stable isotope
      signatures (delta (13)C, delta (15)N, deltaD and delta (34)S) to investigate
      whether malaria infected and non-infected birds had occupied different areas in
      winter. We show that birds moulting in Afro-tropical habitats with significantly
      higher delta (13)C and delta (15)N but lower deltaD and delta(34)S values were
      more frequently infected with malaria parasites. Based on established patterns of
      isotopic distributions, our results indicate that moulting sites with higher
      incidence of malaria are generally drier and situated further to the north in
      West Africa than sites with lower incidence of malaria. Our findings are
      pertinent to the general hypothesis that animal distribution and particularly
      avian migration strategy might evolve in response to selection pressures exerted
      by parasites at different geographic scales. Tradeoffs between investment in
      energy demanding life history traits (e.g. migration and winter moult) and immune
      function are suggested to contribute to the particular choice of habitat during
      migration and at wintering sites.

PMID- 18810502
TI  - The diagnostic value of ultrasound in cystic kidney diseases.
AB  - Renal cysts in childhood can be found in a variety of diseases, which can be
      congenital or acquired, or renal cysts may be part of a multiorgan disease or
      restricted to the kidneys only. Ultrasonography is the first-line diagnostic tool
      and is informative in many cases. However, there is a broad spectrum in the
      sonographic appearance of renal cysts, and family or genetic studies, a search
      for extrarenal organ involvement, or additional imaging modalities may be
      required to make a definitive diagnosis. The aim of this article is to summarize
      the diagnostic potential and limitations of ultrasonography and depict typical
      examples of the most important cystic entities.

PMID- 18810503
TI  - Outcome of dialysis in children with human immunodeficiency virus infection.
AB  - Human immunodeficiency virus (HIV) infection accounts for an unknown percentage
      of children with end-stage kidney disease (ESKD). Our objective was to compare
      the outcome of renal replacement therapy (RRT) in subjects with ESKD due to HIV
      and other diagnoses and to examine the prevalence of ESKD due to HIV. We analyzed
      Kt/V, morbidity, mortality, echocardiography, nutritional, and transplant status
      in 12 dialysis patients with HIV and 32 without HIV followed at our center
      between February 2002 and February 2007. Body mass index (BMI) was lower and Kt/V
      higher in HIV than in non-HIV patients. Shortening fraction was significantly
      lower in HIV patients. There were six deaths in the HIV group and one in the non
      HIV group over the study period. Hemodialysis (HD) is the prevalent mode of RRT
      in HIV in urban settings, and its adequacy as measured by Kt/V was higher in HIV
      patients than in non-HIV patients. Decreased BMI and cardiovascular disease may
      be associated with increased mortality in children with HIV on RRT.

PMID- 18810504
TI  - Artificial neural network models of relationships between Alternaria spores and
      meteorological factors in Szczecin (Poland).
AB  - Alternaria is an airborne fungal spore type known to trigger respiratory allergy
      symptoms in sensitive patients. Aiming to reduce the risk for allergic
      individuals, we constructed predictive models for the fungal spore circulation in
      Szczecin, Poland. Monthly forecasting models were developed for the airborne
      spore concentrations of Alternaria, which is one of the most abundant fungal taxa
      in the area. Aerobiological sampling was conducted over 2004--2007, using a
      Lanzoni trap. Simultaneously, the following meteorological parameters were
      recorded: daily level of precipitation; maximum and average wind speed; relative
      humidity; and maximum, minimum, average, and dew point temperature. The original
      factors as well as with lags (up to 3 days) were used as the explaining
      variables. Due to non-linearity and non-normality of the data set, the modelling
      technique applied was the artificial neural network (ANN) method. The final model
      was a split model with classification (spore presence or absence) followed by
      regression for spore seasons and logx+1 transformed Alternaria spore
      concentration. All variables except maximum wind speed and precipitation were
      important factors in the overall classification model. In the regression model
      for spore seasons, close relationships were noted between Alternaria spore
      concentration and average and maximum temperature (on the same day and 3 days
      previously), humidity (with lag 1) and maximum wind speed 2 days previously. The
      most important variable was humidity recorded on the same day. Our study
      illustrates a novel approach to modelling of time series with short spore
      seasons, and indicates that the ANN method provides the possibility of
      forecasting Alternaria spore concentration with high accuracy.

PMID- 18810505
TI  - Catastrophic bleeds during end-of-life care in haematology: controversies from
      Australian research.
AB  - GOALS OF WORK: This article seeks to address the lack of information in the
      literature, by providing preliminary findings on the experience of managing
      catastrophic bleeds for haematology patients, from the perspective of health
      professionals involved in the care of such patients and their families. MATERIALS
      AND METHODS: Insights from qualitative interviews with seventeen (n = 17)
      haematological nurses, four (n = 4) palliative care nurses and fifteen (n = 15)
      haematologists, conducted as part of a 2-year major national study on haematology
      and palliative care funded by the National Health and Medical Research Council,
      Australia. The interviews were audio-recorded and transcribed verbatim. The
      language texts were coded and analysed thematically. MAIN RESULTS: The findings
      indicate that there is considerable controversy about the provision of clinical
      and supportive care to haematology patients who are vulnerable to catastrophic
      bleeds, including such issues as whether it is possible to identify individuals
      likely to be affected, the role of blood products, and whether it is wise to warn
      family or carers. The insights from the health professionals also highlight a
      number of practical suggestions including: the use of dark towels to reduce the
      distress of the visibility of the bleed; the importance of advance planning for
      care; accepting the limits of the situation; reassuring family that the patient
      is likely to lapse into lack of consciousness and will not be suffering, and the
      administration of sedation. CONCLUSIONS: The important recommendation from this
      research is the resounding need for further work on this topic in order to
      provide clear guideline for best practice in clinical and supportive care.

PMID- 18810506
TI  - Treatment adherence and patients' acceptance of home infusions with adenosine 5'
      triphosphate (ATP) in palliative home care.
AB  - GOALS OF WORK: In preterminal cancer patients, provision of palliative care in
      the patients' own environment is preferred. The aim of the present study was to
      evaluate patients' and caregivers' treatment adherence and patients' acceptance
      of home infusions with adenosine 5'-triphosphate (ATP). PATIENTS AND METHODS:
      Preterminal cancer patients (life expectancy <6 months) with mixed tumor types
      were eligible for the study. Patients received a maximum of eight weekly
      intravenous 8-10 h ATP infusions. Evaluation of treatment adherence was based on
      registration of protocol deviations and patients' acceptance by structured
      interviews with patients. MAIN RESULTS: Fifty-one patients received a total of
      266 intravenous ATP infusions. The infusion protocol was well executed: mean
      duration approximately 8.30 h, stepwise achievement of the maximum infusion rate
      within 30 min in 65% of the infusions, and almost no delay in weekly
      administration. All except one patient were not burdened by the administration of
      the infusions at home and none of them had felt afraid. The majority of patients
      found the advantages of the ATP infusions outweighing the disadvantages. However,
      an important bottleneck in the administration of ATP infusions at home was
      difficulty in establishing venous access. CONCLUSION: ATP infusions at home are
      well accepted by patients. Difficulties in establishing venous access might be
      reduced by composing specialized home infusion teams working both at the day care
      center and at home or by adopting an alternative route of venous access.

PMID- 18810507
TI  - Combined arene ruthenium porphyrins as chemotherapeutics and photosensitizers for
      cancer therapy.
AB  - Mononuclear 5-(4-pyridyl)-10,15,20-triphenylporphyrin and 5-(3-pyridyl)-10,15,20
      triphenylporphyrin as well as tetranuclear 5,10,15,20-tetra(4-pyridyl)porphyrin
      (tetra-4-pp) and 5,10,15,20-tetra(3-pyridyl)porphyrin) (tetra-3-pp) arene
      ruthenium(II) derivatives (arene is C(6)H(5)Me or p-Pr(i)C(6)H(4)Me) were
      prepared and evaluated as potential dual photosensitizers and chemotherapeutics
      in human Me300 melanoma cells. In the absence of light, all tetranuclear
      complexes were cytotoxic (IC(50) < or = 20 microM), while the mononuclear
      derivatives were not (IC(50) > or = 100 microM). Kinetic studies of tritiated
      thymidine and tritiated leucine incorporations in cells exposed to a low
      concentration (5 microM) of tetranuclear p-cymene derivatives demonstrated a
      rapid inhibition of DNA synthesis, while protein synthesis was inhibited only
      later, suggesting arene ruthenium-DNA interactions as the initial cytotoxic
      process. All complexes exhibited phototoxicities toward melanoma cells when
      exposed to laser light of 652 nm. At low concentration (5 microM), LD(50) of the
      mononuclear derivatives was between 5 and 10 J/cm(2), while for the tetranuclear
      derivatives LD(50) was approximately 2.5 J/cm(2) for the [Ru(4)(eta(6)
      arene)(4)(tetra-4-pp)Cl(8)] complexes and less than 0.5 J/cm(2) for the
      [Ru(4)(eta(6)-arene)(4)(tetra-3-pp)Cl(8)] complexes. Examination of cells under a
      fluorescence microscope revealed the [Ru(4)(eta(6)-arene)(4)(tetra-4-pp)Cl(8)]
      complexes as cytoplasmic aggregates, whereas the [Ru(4)(eta(6)-arene)(4)(tetra-3
      pp)Cl(8)] complexes were homogenously dispersed in the cytoplasm. Thus, these
      complexes present a dual synergistic effect with good properties of both the
      arene ruthenium chemotherapeutics and the porphyrin photosensitizer.

PMID- 18810508
TI  - Candida albicans adhesion to composite resin materials.
AB  - The adhesion of Candida albicans to dental restorative materials in the human
      oral cavity may promote the occurrence of oral candidosis. This study aimed to
      compare the susceptibility of 14 commonly used composite resin materials (two
      compomers, one ormocer, one novel silorane, and ten conventional hybrid
      composites) to adhere Candida albicans. Differences in the amount of adhering
      fungi should be related to surface roughness, hydrophobicity, and the type of
      matrix. Cylindrical specimens of each material were made according to the
      manufacturers' instructions. Surface roughness R (a) was assessed by perthometer
      measurements and the degree of hydrophobicity by computerized contact angle
      analysis. Specimens were incubated with a reference strain of C. albicans (DMSZ
      1386), and adhering fungi were quantified by using a bioluminometric assay in
      combination with an automated plate reader. Statistical differences were analyzed
      by the Kruskal-Wallis test and Mann-Whitney U test. Spearman's rank correlation
      coefficients were calculated to assess correlations. Median R (a) of the tested
      composite resin materials ranged between 0.04 and 0.23 microm, median contact
      angles between 69.2 degrees and 86.9 degrees . The two compomers and the ormocer
      showed lower luminescence intensities indicating less adhesion of fungi than all
      tested conventional hybrid composites. No conclusive correlation was found
      between surface roughness, hydrophobicity, and the amount of adhering C.
      albicans.

PMID- 18810509
TI  - Characterisation of lysozyme activity in the in situ pellicle using a
      fluorimetric assay.
AB  - Lysozyme is among the most protective enzymes in the pellicle layer. The aim of
      the present study was to establish a precise fluorimetric assay for determination
      and characterisation of lysozyme activity immobilised in the initial in situ
      formed pellicle. For in situ pellicle formation, bovine enamel slabs were fixed
      on maxillary splints and carried by six subjects for different times (3, 30 min)
      on buccal and palatal sites. The enzymatic assay was based on hydrolysis of cell
      walls from Micrococcus lysodeicticus linked to a fluorogenic substance. When the
      substrate is hydrolysed, a fluorescing product is released. Furthermore, the
      effects of chlorhexidine and black tea on lysozyme in the in situ pellicle were
      investigated. The fluorimetric method allowed direct determination of the enzyme
      activity with the slab inside the well of a microtiter plate. The mean
      immobilised activity over all samples amounted to 68.67 +/- 27.35 U/cm(2)
      (desorbed activity = 46.76 +/- 21.18 U/cm(2)). The enzyme activity exposed at the
      pellicles' surfaces increased in a time-dependant manner and showed a Michaelis
      Menten kinetic. Chlorhexidine and black tea reduced lysozyme activity of the in
      situ pellicle significantly. After rinsing with tea or chlorhexidine, V(max) was
      reduced, whereas K(m) remained unaffected indicating a negative allosteric effect
      of the V type. The fluorimetric method is appropriate for determination of
      pellicle lysozyme activity. The influence of effectors on immobilised lysozyme
      activity can be monitored.

PMID- 18810510
TI  - Association of dopamine transporter and monoamine oxidase molecular polymorphisms
      with sudden infant death syndrome and stillbirth: new insights into the serotonin
      hypothesis.
AB  - Recent findings demonstrated the role of neurotransmitters in the
      aetiopathogenesis of sudden unexpected deaths in infancy. Although genes involved
      in serotonin metabolism have been proposed as risk factors for sudden infant
      death syndrome (SIDS), the contribution of additional neurotransmitters and genes
      different from the serotonin transporter (SLC6A4, 5-HTT) has not been
      investigated. Considering the common metabolic pathway and synergism between
      dopamine and serotonin, the role of dopamine transporter (SLC6A3, DAT) and
      monoamine oxidase A (MAOA) genes in SIDS and stillbirth (sudden intrauterine
      unexplained death, SIUD) was investigated. Genotypes and allelic frequencies of
      DAT and MAOA were determined in 20 SIDS and five stillbirth cases and compared
      with 150 controls. No association was found between DAT polymorphisms and SIDS
      either at genotype (P = 0.64) or allelic (P = 0.86) level; however, a highly
      significant association was found between MAOA genotypes (P = 0.047) and alleles
      (P = 0.002) regulating different expression patterns (3R/3R vs 3.5R/3.5R + 4R/4R)
      in SIDS + SIUD and controls. Analysis of combined 5-HTTLPR (serotonin transporter
      linked polymorphic region)/MAOA genotypes revealed that frequency of L/L-4R/4R
      genotype combination was eightfold higher in SIDS + SIUD than in controls (P <
      0.001). Findings are discussed considering the metabolic association among DAT, 5
      HTT and MAOA with special emphasis on the linked action of 5-HTT/MAOA in
      regulating serotonin metabolism of SIDS and SIUD infants.

PMID- 18810511
TI  - Maternal uniparental heterodisomy with partial isodisomy of a chromosome 2
      carrying a splice acceptor site mutation (IVS9-2A>T) in ALS2 causes infantile
      onset ascending spastic paralysis (IAHSP).
AB  - Infantile-onset ascending spastic paralysis (OMIM #607225) is a rare autosomal
      recessive early onset motor neuron disease caused by mutations in the gene ALS2.
      We report on a splice acceptor site mutation in intron 9 of ALS2 (IVS9-2A>T) in a
      German patient from nonconsanguineous parents. The mutation results in skipping
      of exon 10. This causes a frame-shift in exon 11 and a premature stop codon.
      Analysis of the parental ALS2 gene revealed heterozygosity for the mutation in
      the mother but not in the father. Therefore, we studied polymorphic markers
      scattered along chromosome 2 in both parents and the patient and found maternal
      uniparental disomy in the patient. While homozygosity was observed at several
      loci of chromosome 2 including ALS2, other loci were heterozygous, i.e., both
      maternal alleles were present. The findings can be explained by at least four
      recombination events during maternal meiosis followed by a meiosis I error and
      postzygotic trisomy rescue or gamete complementation.

PMID- 18810512
TI  - Tool use as a way to assess cognition: how do captive chimpanzees handle the
      weight of the hammer when cracking a nut?
AB  - Tool use in apes has been considered a landmark in cognition. However, while most
      studies concentrate on mental operations, there are very few studies of apes'
      cognition as expressed in manual skills. This paper proposes theoretical and
      methodological considerations on movement analysis as a way of assessing primate
      cognition. We argue that a privileged way of appraising the characteristics of
      the cognitive abilities involved in tool use lies at the functional level. This
      implies that we focus on how the action proceeds, and more precisely, on how the
      functional characteristics of the task are generated. To support our view, we
      present the results of an experiment with five captive chimpanzees investigating
      the way how chimpanzees adapt to hammers of various weights while cracking nuts.
      The movement performed in the hammering task is analyzed in terms of energy
      production. Results show that chimpanzees mobilise passive as well as active
      forces to perform the compliant movement, that is, they modulate the dynamics of
      the arm/tool system. A comparison between chimpanzees suggests that experience
      contributes to this skill. The results suggest that in tool use, movements are
      not key per se, but only in as much as they express underlying cognitive
      processes.

PMID- 18810513
TI  - Tsukamurella: a cause of catheter-related bloodstream infections.
AB  - Tsukamurellae are strictly aerobic Gram-positive rods that can be easily
      misidentified as Corynebacterium species, Rhodococcus species, Nocardia species,
      Mycobacterium species, or other Gram-positive aerobic rods. They have been
      uncommonly reported as a cause of different human infections, including
      bloodstream infections. We describe 2 new cases of catheter-related bloodstream
      infections (CR-BSI) caused by Tsukamurella species and review 12 similar cases
      reported in the literature. Conventional procedures have often misidentified
      Tsukamurella species as other aerobic Gram-positive rods. This misidentification
      could be avoided using genotyping. All cases ultimately required the withdrawal
      of the infected line. The literature provides no firm conclusions regarding ideal
      choice or duration of antimicrobial therapy for this infection. Tsukamurella
      species should be added to the list of agents able to produce CR-BSI. Genotypic
      methods such as PCR 16S rRNA can allow a reliable identification at the genus
      level of Tsukamurella strains faster than a combination of conventional
      phenotypic methods.

PMID- 18810514
TI  - T-cell lymphoma mimicking schwannoma of a cervical nerve root.
AB  - T-cell lymphoblastic lymphoma is a rare form of non-Hodgkin lymphoma, which shows
      preponderance for young men. Most common symptoms are painless swelling of lymph
      nodes, accompanied by B symptoms and large mediastinal masses. Most often, an
      involvement of the nervous system is due to paraneoplastic symptoms or side
      effects of treatment. In a literature research, we could not find a case with
      affection of a cervical nerve root as the first symptom for T-cell lymphoblastic
      lymphoma. A 39-year-old man presented with right-sided C8 radiculopathy,
      including pareses and paresthesia. Since the magnetic resonance image disclosed a
      right-sided mass lesion in the region of the neuroforamen C8, compressing the
      corresponding nerve root, a schwannoma was suspected. The tumor was removed using
      a dorsal approach. Neuropathological examination revealed the diagnosis of T-cell
      lymphoblastic lymphoma. The patient underwent diagnostic staging and received
      further treatment. He experienced a very grim course and succumbed to his disease
      12 months after surgery. T-cell lymphoblastic lymphoma is a rare disease, and
      tropism of lymphoma cells to neural structures is seldom encountered. However,
      the presence of radiculopathy, together with signs, referring to B symptoms,
      should prompt the physician to consider this coincidence in the differential
      diagnosis of schwannoma.

PMID- 18810515
TI  - Solid haemangioblastomas of the CNS: a review of 17 consecutive cases.
AB  - A retrospective study on solid central nervous system haemangioblastomas was
      performed to characterize clinical features, treatment strategies and outcome in
      these rare lesions. Between 1993 and 2006 23, solid haemangioblastomas were
      surgically removed in 17 patients. Eight lesions were located within pons Varolii
      and medulla oblongata, six within the cerebellar hemispheres and three in the
      cerebellopontine angle. Three haemangioblastomas were located supratentorially
      and three within the spinal cord. All patients except two underwent pre-operative
      magnetic resonance imaging (MRI). Post-operative digital subtraction angiography
      and/or MRI was performed in all surviving patients. Except for spinal cord
      lesions, rather unsystematic clinical symptoms were observed. Twenty-two tumours
      could be resected completely. Two patients with brainstem lesions died within 10
      weeks after surgery from infectious complications. Persistent new neurological
      deficits occurred in two patients. Three patients underwent radiosurgery prior to
      or following the surgical procedure. Solid haemangioblastomas represent a
      surgical challenge due to their arteriovenous malformation-like vascularisation
      and their frequent location in eloquent areas. Surgery is the therapy of choice.
      Circumferential dissection with devascularization and en bloc removal yields good
      functional results. A location within the brainstem carries the most unfavourable
      prognosis.

PMID- 18810516
TI  - Failure and success of hydrodynamic interaction models.
AB  - In suspensions with charged particles, electrostatic forces and hydrodynamic
      interactions are both important to describe the system. We study different models
      of hydrodynamic interaction for monopolarly charged particles in a non-polar
      liquid. In this case, there is no screening of the Coulomb repulsion, so the
      repulsion between all pairs must be taken into account. The particles are
      expected to drift away from each other, however at a lower rate when hydrodynamic
      interaction between the particles is taken into account. Existing, frequently
      used models of hydrodynamic interactions tend to overestimate the slowing down of
      the charged particles, even to the extent that the particles effectively attract
      each other. This is demonstrated for some selected particle setups. We find that
      these anomalies even occur in dilute systems, if they contain sufficiently many
      particles. We explain why these anomalies can be avoided by an approach, in which
      the superposition of interactions is done in the friction tensor instead of the
      mobility tensor.

PMID- 18810517
TI  - Purification and characterization of extracellular lipases from Pseudomonas
      monteilii TKU009 by the use of soybeans as the substrate.
AB  - A lipase-producing bacterium was isolated and identified as Pseudomonas monteilii
      TKU009. A lipase (F2) and lipase-like materials (F1) were purified from the
      culture supernatant of P. monteilii TKU009 with soybean powder as the sole
      carbon/nitrogen source. The molecular mass of F1 and F2 was estimated to be 44
      kDa by SDS-PAGE and gel filtration. The optimum pH, optimum temperature, and pH
      and thermal stabilities of F2 were 7, 40 degrees C, 8-11, and 50 degrees C; and
      of F1 were 6, 40 degrees C, 6-7, and 50 degrees C, respectively. F2 was
      completely inhibited by EDTA and slightly by Mg(2+), Fe(2+), Mn(2+), and SDS. F1
      was completely inhibited by EDTA and Fe(2+) and strongly by Zn(2+), Mn(2+),
      Ca(2+), Mg(2+), and SDS. The activities of both the enzymes were enhanced by the
      addition of non-ionic surfactants Triton X-100 and Tween 40, especially for F1.
      F2 preferably acted on substrates with a long chain (C10-C18) of fatty acids,
      while F1 showed a broad spectrum on those with chain length of C4-C18. The marked
      activity of F2 in organic solvents makes it an ideal choice for application in a
      water-restricted medium including organic synthesis.

PMID- 18810518
TI  - Production of fructosyltransferase by Aureobasidium sp. ATCC 20524 in batch and
      two-step batch cultures.
AB  - A comparison of fructosyltransferase (EC 2.4.1.9) production by Aureobasidium sp.
      ATCC 20524 in batch and two step batch cultures was investigated in a 1-l stirred
      tank reactor using a sucrose supply of 200 g/l. Results showed that the
      innovative cultivation in two step of Aureobasidium sp. produced more
      fructosyltransferase (FFase) than the single batch culture at the same sucrose
      concentration with a maximal enzyme production of 523 U/ml, which was 80.5%
      higher than the one obtained in the batch culture. The production of
      fructooligosaccharides (FOSs) was also analyzed; their concentration reached a
      maximum value of 160 g/l the first day in the two-step culture and 127 g/l in the
      single-batch mode. The use of the two-step batch culture with Aureobasidium sp.
      ATCC 20524 in allowing the microorganism to grow up prior to the induction of
      sucrose (second step), proved to be a powerful method for producing
      fructosyltransferase and FOSs.

PMID- 18810519
TI  - Reproducibility and consistency of evaluation techniques for HARDI data.
AB  - OBJECT: The reproducibility of three evaluation techniques for high angular
      resolution diffusion imaging (HARDI) data, the diffusion tensor model, q-ball
      reconstruction and spherical deconvolution, are compared. MATERIALS AND METHODS:
      Two healthy volunteers were measured in a 3 T MR system six times with the same
      measurement parameters; one subject was measured with different b-values. The
      data was evaluated to compare the consistency and reproducibility of
      reconstructed diffusion directions and anisotropy values for the three
      investigated diffusion evaluation techniques. The angle difference between the
      reconstructed main directions of diffusion for the investigated techniques was
      evaluated. For q-ball and spherical deconvolution the consistency of the second
      dominant diffusion direction was additionally examined. RESULTS: The differences
      between the tensor model and q-ball or spherical deconvolution in the estimated
      diffusion direction decrease with an increase in fractional anisotropy.
      Increasing the smoothing kernel in q-ball reconstruction renders the results
      similar to the ones from the diffusion tensor evaluation. Consistency in the
      reconstructed directions did increase for larger b-values. CONCLUSION: The
      evaluation of HARDI data in clinical conditions with q-ball or spherical
      deconvolution shows consistency and reproducibility similar to the diffusion
      tensor model, but provides valuable additional information about a second
      dominant direction of diffusion.

PMID- 18810520
TI  - Functional role theories of representation and content explanation: with a case
      study from spatial cognition.
AB  - The aim of this paper is to show that the widespread opinion, according to which
      functional role theories of representation fail to account for content
      explanations of human and animal behaviour, cannot be confirmed with respect to
      each type of functional role theory. Functional resemblance theories (as referred
      to by O'Brien and Opie in Representation in mind, Elsevier, 2004) allow for
      content explanations of successfully performed cognitive abilities as much as for
      explanations of systematic errors resulting from misrepresentation. How
      functional roles do their explanatory work in actual scientific research examples
      is shown by a detailed exploration of model assumptions about homing performances
      based on path integration mechanisms in humans and animals.

PMID- 18810521
TI  - Towards patient-specific risk assessment of abdominal aortic aneurysm.
AB  - Diagnosis of vascular disease and selection and planning of therapy are to a
      large extent based on the geometry of the diseased vessel. Treatment of a
      particular vascular disease is usually considered if the geometrical parameter
      that characterizes the severity of the disease, e.g. % vessel narrowing, exceeds
      a threshold. The thresholds that are used in clinical practice are based on
      epidemiological knowledge, which has been obtained by clinical studies including
      large numbers of patients. They may apply "on average", but they can be sub
      optimal for individual patients. To realize more patient-specific treatment
      decision criteria, more detailed knowledge may be required about the vascular
      hemodynamics, i.e. the blood flow and pressure in the diseased vessel and the
      biomechanical reaction of the vessel wall to this flow and pressure. Over the
      last decade, a substantial number of publications have appeared on hemodynamic
      modeling. Some studies have provided first evidence that this modeling may indeed
      be used to support therapeutic decisions. The goal of the research reported in
      this paper is to go one step further, namely to investigate the feasibility of a
      patient-specific hemodynamic modeling methodology that is not only effective
      (improves therapeutic decisions), but that is also efficient (easy to use, fast,
      as much as possible automatic) and robust (insensitive to variation in the
      quality of the input data, same outcome for different users). A review is
      presented of our research performed during the last 5 years and the results that
      were achieved. This research focused on the risk assessment for one particular
      disease, namely abdominal aortic aneurysm, a life-threatening dilatation of the
      abdominal aorta.

PMID- 18810522
TI  - An evolutionary footprint of age-related natural selection in mitochondrial DNA.
AB  - By comparing mtDNA sequences between different orders of mammals, we show that
      both longevity and generation time are significantly correlated with the
      nucleotide content of the mtDNA. Specifically, there is a positive correlation
      between generation time and mt GC content. This correlation is repeated, at a
      finer evolutionary scale, within the primates. Moreover, a comparison of human
      and chimpanzee mtDNAs shows that the effect has been very pronounced during the
      short evolutionary period since the divergence of these two species, with human
      mtDNA showing a GC-biased pattern of substitution at the variable sites. In
      addition to these DNA sequence patterns, comparisons between the human and the
      chimp mt protein sequences also revealed a surprisingly high substitution rate
      for threonine residues, resulting in a reduction of threonine in the human mt
      proteome. These patterns of both DNA and protein evolution can be explained by a
      balance between AT-biased mutational pressure and age-related purifying
      selection.

PMID- 18810523
TI  - The universal trend of amino acid gain-loss is caused by CpG hypermutability.
AB  - Understanding the cause of the changes in the amino acid composition of proteins
      is essential for understanding the evolution of protein functions. Since the
      early 1970s, it has been known that the frequency of some amino acids in protein
      sequences is increasing and that of others is decreasing. Recently, it was found
      that the trends of amino acid changes were similar in 15 taxa representing
      Bacteria, Archaea, and Eukaryota. However, the cause of this similarity in the
      trend of the gains and losses of amino acids continued to be debated. Here, we
      show that this trend of the gain and loss of amino acids can be simply explained
      by CpG hypermutability. We found that the frequency of amino acids coded by
      codons with TpG dinucleotides and those with CpA dinucleotides is increasing,
      while that of amino acids coded by codons with CpG dinucleotides is decreasing.
      We also found that organisms that lack DNA methyltransferase show different
      trends of the gain and loss of amino acids. DNA methyltransferase methylates CpG
      dinucleotides and induces CpG hypermutability. The incorporation of CpG
      hypermutability into models of protein evolution will improve studies on protein
      evolution in different organisms.

PMID- 18810524
TI  - Human-carnivore coexistence on communal land bordering the greater Kruger area,
      South Africa.
AB  - The aim of this study was to assess the potential for coexistence between rural
      people (living adjacent to a protected area) and predators (from the same area)
      ranging onto communal land. Ninety members of local communities bordering
      Manyeleti Game Reserve, which is contiguous with Kruger National Park, South
      Africa were interviewed. Respondents expressed diverging attitudes toward
      predators, which were more favorable among participants with higher education.
      Negative views were particularly due to fear of human and livestock losses,
      especially to lions, Panthera leo. Lions were thought to be the most abundant
      predator both within and outside the reserve. Lions were also the best known
      predator and were most often held responsible for killing livestock. Despite
      these livestock losses and a lack of conservation education, most participants
      voiced favorable opinions about large carnivore conservation, as predators were
      considered an integral part of the respondents' natural heritage. Thanks to this
      cultural tolerance and also because of a largely accepted management policy
      regarding predator control, large carnivores and people can coexist in the
      vicinity of Kruger National Park.

PMID- 18810525
TI  - Managing dive tourism for the sustainable use of coral reefs: validating diver
      perceptions of attractive site features.
AB  - It has been argued that strategies to manage natural areas important for tourism
      and recreation should integrate an understanding of tourist preferences for
      specific natural features. However, the accuracy of tourist recalled perceptions
      of environmental attributes, which are usually derived from post hoc surveys and
      used to establish management priorities, is currently unmeasured. We tested the
      validity of the relationship between tourist-stated preferences and actual
      condition of coral reefs around the Caribbean island of Bonaire. Using
      standardized questionnaires, we asked 200 divers to select their most and least
      favorite dive sites and the attributes that contributed to that selection. We
      also carried out ecological surveys at 76 of the 81 dives sites around the island
      to assess the actual conditions of the attributes indicated as important for site
      selection. Fish- and coral-related attributes were key features affecting dive
      enjoyment. In general, divers appeared to be able to perceive differences between
      sites in the true condition of biological attributes such as fish species
      richness, total number of fish schools, live coral cover, coral species richness,
      and reef structural complexity, although men and women divers differed in their
      ability to perceive/recall some of the attributes. Perceived differences in
      environmental attributes, such as surface conditions, underwater current, and the
      likelihood of encountering rare fish and sea turtles, were not empirically
      validated. The fact that divers perceive correctly differences in the condition
      of some of the key biological attributes that affect dive enjoyment reinforces
      the need to maintain overall reef condition at satisfactory levels. However,
      variation in accuracy of perceptions owing to demographic factors and attribute
      type suggests the need for caution when using public perceptions to develop
      environmental management strategies, particularly for coral reefs.

PMID- 18810526
TI  - Farmers' perceptions of climate change and agricultural adaptation strategies in
      rural Sahel.
AB  - Farmers in the Sahel have always been facing climatic variability at intra- and
      inter-annual and decadal time scales. While coping and adaptation strategies have
      traditionally included crop diversification, mobility, livelihood
      diversification, and migration, singling out climate as a direct driver of
      changes is not so simple. Using focus group interviews and a household survey,
      this study analyzes the perceptions of climate change and the strategies for
      coping and adaptation by sedentary farmers in the savanna zone of central
      Senegal. Households are aware of climate variability and identify wind and
      occasional excess rainfall as the most destructive climate factors. Households
      attribute poor livestock health, reduced crop yields and a range of other
      problems to climate factors, especially wind. However, when questions on land use
      and livelihood change are not asked directly in a climate context, households and
      groups assign economic, political, and social rather than climate factors as the
      main reasons for change. It is concluded that the communities studied have a high
      awareness of climate issues, but climatic narratives are likely to influence
      responses when questions mention climate. Change in land use and livelihood
      strategies is driven by adaptation to a range of factors of which climate appears
      not to be the most important. Implications for policy-making on agricultural and
      economic development will be to focus on providing flexible options rather than
      specific solutions to uncertain climate.

PMID- 18810528
TI  - The anterior branch of the left inferior phrenic artery arising from the right
      inferior phrenic artery: an angiographic and CT study.
AB  - The purpose of this study was to retrospectively analyze the frequency and
      anatomical pattern of the anterior branch of the left inferior phrenic artery
      (LIPA) arising from the right inferior phrenic artery (RIPA). Angiography of the
      RIPA for patients (n = 140) with hepatic malignancy was retrospectively reviewed.
      The frequency at which the anterior branch of the LIPA arose from the RIPA was
      14.3% (20 of 140 patients [pts]). Among the three branches that may arise from
      the RIPA in these cases (the anterior branch of the LIPA and the anterior and
      posterior branches of the RIPA), the anterior branch of the LIPA was the first
      branch of the RIPA in 9 of 20 pts (45%), and the posterior branch of the RIPA in
      11 of 20 pts (55%). The anterior branch of the LIPA ran along the ventral side of
      the esophagus or stomach and supplied the esophagogastric region and dome of the
      left diaphragm in all cases. In conclusion, the anterior branch of the LIPA
      arises from the RIPA at a comparatively high frequency. In embolization of the
      RIPA, to effectively treat and avoid possible complications, interventionalists
      should be aware of this potential variant anatomy.

PMID- 18810527
TI  - Projecting cumulative benefits of multiple river restoration projects: an example
      from the Sacramento-San Joaquin River system in California.
AB  - Despite increasingly large investments, the potential ecological effects of river
      restoration programs are still small compared to the degree of human alterations
      to physical and ecological function. Thus, it is rarely possible to "restore" pre
      disturbance conditions; rather restoration programs (even large, well-funded
      ones) will nearly always involve multiple small projects, each of which can make
      some modest change to selected ecosystem processes and habitats. At present, such
      projects are typically selected based on their attributes as individual projects
      (e.g., consistency with programmatic goals of the funders, scientific soundness,
      and acceptance by local communities), and ease of implementation. Projects are
      rarely prioritized (at least explicitly) based on how they will cumulatively
      affect ecosystem function over coming decades. Such projections require an
      understanding of the form of the restoration response curve, or at least that we
      assume some plausible relations and estimate cumulative effects based thereon.
      Drawing on our experience with the CALFED Bay-Delta Ecosystem Restoration Program
      in California, we consider potential cumulative system-wide benefits of a
      restoration activity extensively implemented in the region: isolating/filling
      abandoned floodplain gravel pits captured by rivers to reduce predation of
      outmigrating juvenile salmon by exotic warmwater species inhabiting the pits. We
      present a simple spreadsheet model to show how different assumptions about gravel
      pit bathymetry and predator behavior would affect the cumulative benefits of
      multiple pit-filling and isolation projects, and how these insights could help
      managers prioritize which pits to fill.

PMID- 18810529
TI  - Combined endoscopic and percutaneous treatment of a duodenocutaneous fistula
      using an Amplatzer septal occluder.
AB  - We describe an innovative interventional technique for the repair of a
      postoperative enterocutaneous fistula (ECF). In the reported case, surgical
      repair of the ECF was contraindicated, while endoscopic closure was unsuccessful.
      Correction of this high-outflow fistula was achieved using an Amplatzer septal
      occluder, which was deployed under simultaneous fluoroscopic and endoscopic
      guidance. The use of an Amplatzer septal occluder should be taken into
      consideration when there is a need to treat high-outflow ECF in patients who
      cannot undergo surgery.

PMID- 18810530
TI  - Coronary events and anatomy after arterial switch operation for transposition of
      the great arteries: detection by 16-row multislice computed tomography
      angiography in pediatric patients.
AB  - The purpose of this study was to evaluate the feasibility of multislice computed
      tomographic (MSCT) angiography as a noninvasive method for detecting ostial,
      proximal, and middle segment coronary stenosis or occlusion and anatomy in
      patients with transposition of the great arteries who had undergone arterial
      switch operation (ASO). Sixteen-detector-row MSCT angiography was performed in 16
      patients treated with ASO for transposition of the great arteries. The median age
      was 10.3 years (range, 6.2-16.3 years). Sixteen-detector-row MSCT angiography was
      performed in 16 patients who had undergone ASO. CT imaging was performed in the
      craniocaudal direction from 2 cm above the carina up to the heart basis.
      Noninvasive assessment of coronary artery stenosis and anatomy were investigated
      by MSCT angiography. Two patients were excluded from the study because of
      artifacts. Of 14 evaluated patients, 1 patient had ostial stenosis (7.1%). A
      coronary artery anatomy variant was present in six patients: left main artery
      (LMA) and right coronary artery (RCA) originating from the right sinus as a
      single orifice (n = 2); left circumflex artery (LCX) originating from the RCA (n
      = 1); LMA and RCA, after branching to the LCX, originating separately from the
      right sinus (n = 1); and LMA (n = 1) and left anterior descending artery (LADA; n
      = 1) originating directly from the right sinus. Intramural bridging in the LAD (n
      = 2) was detected. Five patients were normal. In conclusion, MSCT angiography, as
      a noninvasive, feasible technique for assessing coronary stenosis or occlusion
      and anatomy, can be used in the follow-up of patients who have undergone ASO.

PMID- 18810531
TI  - Customized tapered stent-grafts in the endovascular management of internal iliac
      artery aneurysms: a useful adjunct to conventional endovascular options.
AB  - The endovascular exclusion of an isolated iliac artery aneurysm is recognized as
      a safe and favorable alternative to open surgical repair, with low associated
      morbidity and mortality. It has particular advantages in the treatment of
      internal iliac artery aneurysm (IIAA) given the technical difficulties associated
      with open surgical repair deep within the pelvis. We describe the use of
      customized tapered stent-grafts in the exclusion of wide-necked IIAA in five male
      patients considered high-risk for conventional surgical repair, in whom the
      common and external iliac artery morphology precluded the use of standard
      endovascular devices. In each case, IIAA outflow was selectively embolized and
      the aneurysm neck excluded by placement of a customized tapered stent-graft
      across the internal iliac artery origin. This technique was extremely effective,
      with 100% technical success, no serious associated morbidity, and zero mortality.
      In all five patients sac size was stable or reduced on computed tomography follow
      up of up to 3 years (mean, 24.4 months), with a primary patency rate of 100%. We
      therefore advocate the use of customized tapered stent-grafts as a further
      endovascular option in the management of IIAA unsuitable for conventional
      endovascular repair.

PMID- 18810532
TI  - Interference of Lactobacillus plantarum strains in the in vitro conjugative
      transfer of R-plasmids.
AB  - Probiotic compounds, which are often constituted of lactobacilli, exert a number
      of health benefits through maintenance of the intestinal ecosystem balance. Among
      the important interactions that occur in the gut microbiota, plasmid transfer by
      mating is an increasing cause of concern, particularly when antibiotic-resistant
      genes are involved. Because lactobacilli seem to be able to influence this
      mechanism, the aim of the present work was to investigate the in vitro capability
      of two Lactobacillus plantarum strains (one bacteriocin producer and one
      nonproducer) to interfere with the conjugation processes. For this purpose
      different matings were performed adding to the donor and recipient cells L.
      plantarum 35d bac+ and L. plantarum 396/1 bac- as agents of interference.
      Conjugations added with a Staphylococcus aureus strain or without any agent of
      interference were used as controls. The results of our experiments demonstrated
      that both lactobacillus strains were able to decrease mating frequency.
      Statistically significant differences in the viable transconjugants were obtained
      in the presence and in the absence of the lactobacilli. The effect was almost the
      same with the two L. plantarum independent of bacteriocin production. In the
      trial performed with S. aureus, no decrease in mating frequency was observed,
      confirming that the capability to interfere with R-plasmid transfer ability could
      be a property of the tested L. plantarum strains.

PMID- 18810533
TI  - A rapid and easy method for the detection of microbial cellulases on agar plates
      using gram's iodine.
AB  - Screening for cellulase-producing microorganisms is routinely done on
      carboxymethylcellulose (CMC) plates. The culture plates are flooded either with
      1% hexadecyltrimethyl ammonium bromide or with 0.1% Congo red followed by 1 M
      NaCl. In both cases, it takes a minimum of 30 to 40 minutes to obtain the zone of
      hydrolysis after flooding, and the hydrolyzed area is not sharply discernible. An
      improved method is reported herein for the detection of extracellular cellulase
      production by microorganisms by way of plate assay. In this method, CMC plates
      were flooded with Gram's iodine instead of the reagents just mentioned. Gram's
      iodine formed a bluish-black complex with cellulose but not with hydrolyzed
      cellulose, giving a sharp and distinct zone around the cellulase-producing
      microbial colonies within 3 to 5 minutes. The new method is rapid and efficient;
      therefore, it can be easily performed for screening large numbers of microbial
      cultures of both bacteria and fungi. This is the first report on the use of
      Gram's iodine for the detection of cellulase production by microorganisms using
      plate assay.

PMID- 18810534
TI  - Exopolymer biosynthesis and proteomic changes of Pseudomonas sp. HK-6 under
      stress of TNT (2,4,6-trinitrotoluene).
AB  - Scanning electron microscopy revealed pores and wrinkles on the surface of
      Pseudomonas sp. HK-6 cells grown in Luria Bertani (LB) medium containing 0.5 mM
      TNT (2,4,6-trinitrotoluene). Exopolymer connections were also observed on the
      wild-type HK-6 cells but not on the algA mutant cells. In addition, the amount of
      exopolymer from HK strain increased from 90 to 210 microg/mL under TNT stress,
      whereas the algA mutant produced approximately 30 microg/mL, and its exopolymer
      production was little increased by TNT stress. These results indicate that TNT
      stress induced exopolymer production with alginate as a major component. The algA
      mutant degraded TNT more slowly than the wild-type HK-6 strain. HK-6 was able to
      completely degrade 0.5 mM TNT within 8 days, whereas algA mutant only achieved
      approximately 40% within the same time period. Even after 20 days, no more than
      80% of TNT was degraded. According to analyses of proteomes of HK-6 and algA
      mutant cells grown under TNT stress or no stress, several proteins (KinB, AlgB,
      Alg8, and AlgL) in alginate biosynthesis were only highly induced by both strains
      under TNT stress. Interestingly, two stress-shock proteins (SSPs), GroEL and
      RpoH, were more highly expressed in the algA mutant than the HK-6 strain. The
      algA mutant was rendered more vulnerable to environmental stress and had reduced
      ability to metabolize TNT in the absence of alginate synthesis.

PMID- 18810535
TI  - Phylogenetic placement of pentatomid stink bug gut symbionts.
AB  - Insect bacterial symbionts are ubiquitous, however, only a few groups of host
      families have been well studied in relation to their associations with microbes.
      The determination of the phylogenetic relationships among bacteria associated
      with different species within an insect family can provide insights into the
      biology and evolution of these interactions. We studied the phylogenetic
      placement of vertically transmitted bacterial symbionts associated with the
      posterior midgut (crypt-bearing) region of pentatomid stink bugs (Hemiptera,
      Pentatomidae). Our results demonstrate that different host species carried one
      major bacterium in their midgut. Phylogenetic analyses of the 16S rRNA gene
      sequences obtained from the midgut of stink bugs placed all symbionts in a clade
      with Erwinia and Pantoea species, both plant-associated bacteria. Results
      indicate that symbiont monophyly occurs among recently diverged taxa (e.g.,
      within a genus) but does not occur in the Pentatomidae. Results suggest that
      these vertically transmitted symbionts are occasionally replaced by other
      taxonomically similar bacteria over evolutionary time. Our findings highlight how
      the evolutionary history of hemipteran symbionts in unexplored host families may
      have unpredictable levels of complexity.

PMID- 18810536
TI  - Construction and expression of a eukaryotic expression vector containing a fusion
      gene of the Hantaan virus S gene and hsp70 gene.
AB  - Hantavirus (HV) infection leads to a kind of severe systematic syndrome,
      hemorrhagic fever with renal syndrome (HFRS). Heat shock proteins (HSPs) can be
      used as adjuvants assisting soluble antigens to produce specific targets which
      can be attacked by cytotoxic T lymphocytes. For further research on HFRS vaccine,
      this study aimed to express Hantaan virus nucleocapsid protein (HTNV NP)-HSP70
      fusion protein in COS-7 cells. First, an HTNV S gene encoding NP was amplified by
      PCR with a mutated termination code and cloned into eukaryotic expression vector
      pCDNA3.1(+), into which the full-length hsp70 gene had already been inserted, to
      form the S-hsp70 fusion expression vector pCDNA3.1(+)/S-hsp70. Then this
      recombinant plasmid was transfected into COS-7 cells by liposome, and eukaryotic
      expression of NP-HSP70 fusion protein was detected by immunocytochemistry and
      western blot. The results show that the eukaryotic expression vector
      pCDNA3.1(+)/S-hsp70 was successfully constructed and the NP-HSP70 fusion protein
      was effectively expressed in COS-7 cells. This study demonstrates that the NP
      HSP70 fusion protein was expressed effectively from the pCDNA3.1(+)/S-hsp70
      vector in a eukaryotic system and thus provides a basis for using this plasmid as
      a new DNA vaccine against HV infection.

PMID- 18810537
TI  - Self-purificatory Ganga water facilitates death of pathogenic Escherichia coli
      O157:H7.
AB  - Concern over the prevalence of active pharmaceutical agents and subsequent
      occurrence of antimicrobial resistance in the environment is increasing.
      Incorruptible ability of Ganga water was evaluated using fresh, 8-year-old, and
      16-year-old Ganga water samples spiked with pathogenic Escherichia coli serotype
      O157:H7. Survival of E. coli O157:H7 over the course of the experiment was 3, 7,
      and 15 days for fresh, 8-year-old, and 16-year-old Ganga waters, respectively. On
      the contrary, in Milli Q water the decline in viable count of E. coli O157:H7 up
      to 30 days was only 2 log units. Survival of E. coli O157:H7 was greater in
      boiled water compared with water after passage through a 0.2-microm-pore-size
      membrane filter, indicating involvement of heat-labile agents influencing
      survival of E. coli O157:H7 in Ganga water, which seems to indicate the role of
      antimicrobial peptides. Functional diversity of Ganga water's native microbial
      community structure as assessed with Biolog Eco plates was not affected even in
      the presence of a 5-fold log units higher pathogenic load of E. coli O157:H7.
      These findings suggest that Ganga water has certain novel antimicrobial
      attributes, besides its remarkable fluidity, which may provide a much-needed
      basis for the development of new antimicrobial compounds.

PMID- 18810538
TI  - Proteolytic activity from an alkali-thermotolerant Streptomyces gulbargensis sp.
      nov.
AB  - Multiple proteases were produced and partially purified from an alkali
      thermotolerant novel species of Streptomyces (i.e., Streptomyces gulbargensis DAS
      131) after 48 h of growth at 45 degrees C. The enzyme preparation exhibited
      activity over a broad range of pH (4-12) and temperature (27-55 degrees C).
      Optimum activity was observed at a pH of 9.0 and a temperature of 45 degrees C.
      Starch and protease peptone was found to be a good source of carbon and nitrogen
      to enhance the enzyme activity. Two active zones in the range of 19 to 35 kDa
      were detected on sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS
      PAGE).

PMID- 18810539
TI  - Influence of N-terminal truncations on the functional expression of Bacillus
      licheniformis gamma-glutamyltranspeptidase in recombinant Escherichia coli.
AB  - The full-length Bacillus licheniformis gamma-glutamyltranspeptidase (BlGGT) gene
      and six truncations lacking 36, 129, 132, 135, 144, and 174 bp, respectively, at
      the 5' end were prepared by polymerase chain reaction and cloned into the
      expression vector pQE-30. Isopropyl-beta-D-thiogalactopyranoside induction of
      Escherichia coli M15 cells bearing the recombinant plasmids resulted in the
      overexpression of His(6)-tagged proteins BlGGT, BlGGT/DeltaN12, BlGGT/DeltaN43,
      BlGGT/DeltaN44, BlGGT/DeltaN45, BlGGT/DeltaN48, and BlGGT/DeltaN58. Except for
      BlGGT/DeltaN58, the overexpressed enzymes could be purified to near-homogeneity
      by Ni(2+)-NTA resin. The molecular masses of the precursor and subunits of BlGGT,
      BlGGT/DeltaN12, and BlGGT/DeltaN43 were determined to be 63, 41, and 22 kDa,
      respectively, by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, but
      other recombinant enzymes exhibited predominantly as a precursor form. The
      specific activity for purified BlGGT, BlGGT/DeltaN12, BlGGT/DeltaN43, and
      BlGGT/DeltaN44 was 51.9+/-5.6, 1.3+/-0.2, 0.8+/-0.05, and 0.2+/-0.03 U/mg
      protein, respectively, whereas the remaining two enzymes had shown no GGT
      activity under the enzyme assay conditions. BlGGT, BlGGT/DeltaN12,
      BlGGT/DeltaN43, and BlGGT/DeltaN44 could process autocatalytically their
      precursors into alpha- and beta-subunits at 4 degrees C. These results indicate
      that removal of the signal peptide significantly affects the functional
      expression of BlGGT in recombinant E. coli.

PMID- 18810540
TI  - Growth of halotolerant food spoiling yeast Debaryomyces nepalensis NCYC 3413
      under the influence of pH and salt.
AB  - Debaryomyces nepalensis, a halotolerant food-spoiling yeast could grow in complex
      (YEPD) medium at different pHs ranging between 3.0 and 11.0 in the absence of
      salt and at pH 3.0-9.0 in the presence of different concentrations of NaCl and
      KCl. The specific growth rate of D. nepalensis was not affected by the initial pH
      of the medium in the absence of salts, whereas it was affected in the presence of
      salts. At 2 M NaCl and KCl, the organism exhibited a synergistic effect on pH and
      salt stress, which was unique in the Debaryomyces species. Irrespective of the
      initial pH and salt, the intracellular pH of D. nepalensis was approximately 7.0.
      Significant organic acid was produced at neutral and alkaline pH and organic acid
      production increased with the increase in pH and salt. Very specific organic
      acids are produced in the presence of NaCl and KCl. Our observation would
      contribute to a better understanding of the physiological phenomenon of
      halotolerance in D. nepalensis.

PMID- 18810541
TI  - Identification of a nitroalkane oxidase gene: naoA related to the growth of
      Streptomyces ansochromogenes.
AB  - naoA, encoding a nitroalkane oxidase that can catalyze toxic nitroalkanes to
      their corresponding aldehydes or ketones and hydrogen peroxide, was cloned from
      Streptomyces ansochromogenes, but its function related to the growth of
      Streptomyces is unknown. naoA was disrupted by the insertion of a kanamycin
      resistance gene; the resulting strain can grow earlier than a wild-type strain
      under the same conditions. It was shown that naoA disruption accelerated growth
      of the naoA-disruption mutant, which could restore its phenotype and morphology
      as a wild-type strain by complementation of a single copy number of naoA inserted
      into the chromosome. The introduction of an extra copy of naoA into the wild-type
      strain resulted in delayed growth. The result suggested that naoA is an important
      gene related to the growth of S. ansochromogenes.

PMID- 18810542
TI  - Effects of cations and pH on antimicrobial activity of thanatin and s-thanatin
      against Escherichia coli ATCC25922 and B. subtilis ATCC 21332.
AB  - This study analyzes the in vitro effects of cations and pH on antimicrobial
      activity of thanatin and s-thanatin against Escherichia coli ATCC25922 and B.
      subtilis ATCC21332. Thanatin and s-thanatin were synthesized by the solid-phase
      method using a model 432A synthesizer. The bacterial strains tested included two
      antibiotic-susceptible strains of Escherichia coli ATCC25922 and B. subtilis
      ATCC21332. Susceptibility determinations were carried out either in a variety of
      cation concentrations or in pH conditions from pH 5 to pH 8. NaCl or KCl was
      added to the media to final concentrations of 0, 10, 50, 100, 200, and 500 mM,
      whereas CaCl(2) and MgCl(2) were added to the media to final concentrations of 0,
      1, 2, 5, 10, and 20 mM. The antimicrobial activity of thanatin and s-thanatin
      against Escherichia coli ATCC25922 and B. subtilis ATCC21332 decreased, as
      indicated by the increasing minimal inhibitory concentrations (MICs) of both
      peptides with increasing concentrations of Na(+)/K(+)/Ca(2+)/Mg(2+). Both
      peptides lost their activities at 500 mM Na(+)/K(+) but retained them at 20 mM
      Ca(2+)/Mg(2+). Both peptides have MICs that are not significantly different at a
      variety of pH levels, with the antimicrobial activity slightly higher in neutral
      or slightly basic media than under acidic conditions. The antimicrobial peptides
      thanatin and s-thanatin, which have an anti-parallel beta-sheet constrained by
      disulfide bonds, were salt sensitive against both Gram-positive and Gram-negative
      pathogens in vitro. Determining the reason why the thanatins are salt sensitive
      would be useful to provide an understanding of how thanatin and s-thanatin kill
      bacteria. Further investigation of the antimicrobial properties of these peptides
      is warranted.

PMID- 18810543
TI  - Identification of a potential lead structure for designing new antimicrobials to
      treat infections caused by Staphylococcus epidermidis-resistant strains.
AB  - Bacterial infections are a significant cause of morbidity and mortality among
      critically ill patients. The increase of antibiotic resistance in bacteria from
      human microbiota-such as Staphylococcus epidermidis, an important nosocomial
      pathogen that affects immunocompromised patients or those with indwelling devices
      increased the desire for new antibiotics. In this study we designed, synthesized,
      and determined the antimicrobial activity of 27 thieno[2,3-b]pyridines (1, 2, 2a
      2m, 3, 3a-3m) derivatives against a drug-resistant clinical S. epidermidis
      strain. In addition, we performed a structure-activity relationship analysis
      using a molecular modeling approach, and discuss the drug absorption,
      distribution, metabolism, excretion, and toxicity profile and Lipinski's "rule of
      five," which are tools to assess the relationship between structures and drug
      like properties of active compounds. Our results showed that compound 3b (5-(1H
      tetrazol-5-yl)-4-(3;-methylphenylamino)thieno[2,3-b]pyridine) was as active as
      oxacillin and chloramphenicol but with lower theoretical toxicity risks and a
      better drug likeness and drug score potential than chloramphenicol. All molecular
      modeling and biological results reinforced the promising profile of 3b for
      further experimental investigation and development of new antibacterial drugs.

PMID- 18810544
TI  - Proficiency-gain curve for an advanced laparoscopic procedure defined by
      observation clinical human reliability assessment (OCHRA).
AB  - BACKGROUND: There is no established method for defining when a surgeon reaches
      the proficiency plateau in performing a specific operation. The published
      literature refers to "learning curves" based on retrospective evaluation of
      operative time, conversion rates, morbidity etc., which lack objectivity and do
      not address individual human factors. A more useful study of the gain in
      proficiency by the individual surgeon for a particular operation may be obtained
      using observational clinical-human reliability assessment (OCHRA). METHODS:
      Following an 8-month fellowship in advanced laparoscopic surgery, the surgeon
      M.T. performed, independently at his own hospital, a prospective series of 20
      palliative bypass operations for advanced gastric or pancreatic cancer. Unedited
      videotapes of gastro-jejunostomy (GJ) or cholecysto-jejunostomy (CJ) were
      analyzed independently in the training institution by the OCHRA technique.
      RESULTS: For this surgeon proficiency in executing laparoscopic palliative bypass
      was reached after the 14th anastomosis when efficient execution (reduction in
      operative time) was accompanied by significant reduction in technical errors and
      improved economy of movement (reduction of the economy of movement index from 7-5
      to 3-2). The majority of errors were enacted in component tasks associated with
      intracorporeal suturing. The declining incidence of these errors with experience
      was an integral component of the proficiency-gain curve. The important
      performance-shaping factors identified were: concentration lapses (n=1,321),
      misjudgments (n=209), poor camera work (n=193), fatigue (n=128), and impaired
      coordination (n=108). CONCLUSIONS: This study has confirmed that OCHRA can
      describe quantitatively the proficiency-gain curve for a laparoscopic operation
      and indicate the plateau stage when the individual surgeon attains maximal
      performance in the execution of a specific procedure.

PMID- 18810545
TI  - A study of intragastric and intravesicular pressure changes during rest,
      coughing, weight lifting, retching, and vomiting.
AB  - BACKGROUND: In patients undergoing a variety of procedures, surgical success is
      in part dependent on maintaining normal intra-abdominal pressure in the immediate
      postoperative period. Our objective was to quantify intragastric and
      intravesicular pressures during activities, through the use of manometry
      catheters. METHODS: Ten healthy volunteers had a manometry catheter placed
      transnasally, and a urinary Foley catheter placed. Baseline intragastric and
      intravesicular pressures were recorded and the catheters were then transduced
      continuously. Pressures were recorded with activity: coughing, lifting weights,
      retching (dry heaving), and vomiting. RESULTS: All pressure changes were
      significant from baseline except for weight lifting. The highest intragastric
      pressure was 290 mmHg, seen during vomiting. Comparison of intragastric and
      intravesicular pressures showed no significant difference. There was
      significantly higher intragastric pressure with vomiting and retching as compared
      with coughing, whereas coughing applied more pressure than weight lifting.
      CONCLUSIONS: This is the first report of intragastric pressures during vomiting
      and retching (dry heaving). We conclude that vomiting and retching (dry heaving)
      can render significant forces on any tissue apposition within the stomach or the
      peritoneal cavity.

PMID- 18810546
TI  - Is smaller necessarily better? A systematic review comparing the effects of
      minilaparoscopic and conventional laparoscopic cholecystectomy on patient
      outcomes.
AB  - BACKGROUND: In recent years, minilaparoscopic cholecystectomy (MLC; total size of
      trocar incision < 25 mm) has been increasingly advocated for the removal of the
      gallbladder, due to potentially better surgical outcomes (e.g., better cosmetic
      result, reduced pain, shorter hospital stay, quicker return to activity), but an
      evidence-based approach has been lacking. The current systematic review was
      undertaken to evaluate the importance of total size of trocar incision in
      improving surgical outcomes in adult laparoscopic cholecystectomy (LC). METHODS:
      The literature was systematically reviewed using MEDLINE and EmBASE. Only
      randomized controlled trials in English, investigating minilaparoscopic versus
      conventional LC (total size of trocar incision > or = 25 mm) and reporting pain
      scores were included. Quantitative analyses (meta-analyses) were performed on
      postoperative pain scores and other patient outcomes from more than one study
      where feasible and appropriate. Qualitative analyses consisted of assessing the
      number of studies showing a significant difference between the techniques.
      RESULTS: Thirteen trials met the inclusion criteria. There was a trend towards
      reduced pain with MLC compared with conventional LC, without reduction in opioid
      use. Patients in the MLC group had slightly reduced length of hospital stay, but
      there were no significant differences for return to activity. The two
      interventions were also similar in terms of operating times and adverse events,
      but MLC was associated with better cosmetic result (largely patient rated). There
      was a significantly greater likelihood of conversion to conventional LC or to
      open cholecystectomy in the MLC group than there was of conversion to open
      cholecystectomy in the conventional LC group [OR 4.71 (95% confidence interval
      2.67-8.31), p < 0.00001]. CONCLUSIONS: The data included in this review suggest
      that reducing the size of trocar incision results in some limited improvements in
      surgical outcomes after LC. However, it carries a higher risk of conversion to
      conventional LC or open cholecystectomy.

PMID- 18810547
TI  - Low-pressure pneumoperitoneum versus standard pneumoperitoneum in laparoscopic
      cholecystectomy, a prospective randomized clinical trial.
AB  - BACKGROUND: Post-laparoscopic pain syndrome is well recognized and characterized
      by abdominal and particularly shoulder tip pain; it occurs frequently following
      laparoscopic cholecystectomy. The etiology of post-laparoscopic pain can be
      classified into three aspects: visceral, incision, and shoulder. The origin of
      shoulder pain is only partly understood, but it is commonly assumed that the
      cause is overstretching of the diaphragmatic muscle fibers owing to a high rate
      of insufflations. This study aimed to compare the frequency and intensity of
      shoulder tip pain between low-pressure (7 mmHg) and standard-pressure (14 mmHg)
      in a prospective randomized clinical trial. METHODS: One hundred and forty
      consecutive patients undergoing elective laparoscopic cholecystectomy were
      randomized prospectively to either high- or low-pressure pneumoperitoneum and
      blinded by research nurses who assessed the patients during the postoperative
      period. The statistical analysis included sex, mean age, weight, American Society
      of Anesthesiologists (ASA) grade, operative time, complication rate, duration of
      surgery, conversion rate, postoperative pain by using visual analogue scale,
      number of analgesic injections, incidence and severity of shoulder tip pain, and
      postoperative hospital stay. p < 0.05 was considered indicative of significance.
      RESULTS: The characteristics of the patients were similar in the two groups
      except for the predominance of males in the standard-pressure group (controls).
      The procedure was successful in 68 of 70 patients in the low-pressure group
      compared with in 70 patients in the standard group. Operative time, number of
      analgesic injections, visual analogue score, and length of postoperative days
      were similar in both groups. Incidence of shoulder tip pain was higher in the
      standard-pressure group, but not statistically significantly so (27.9% versus
      44.3%) (p = 0.100). CONCLUSIONS: Low-pressure pneumoperitoneum tended to be
      better than standard-pressure pneumoperitoneum in terms of lower incidence of
      shoulder tip pain, but this difference did not reach statistical significance
      following elective laparoscopic cholecystectomy.

PMID- 18810548
TI  - Laparoscopic totally extraperitoneal inguinal hernia repair: lessons learned from
      3,100 hernia repairs over 15 years.
AB  - BACKGROUND: Two revolutions in inguinal hernia repair surgery have occurred
      during the last two decades. The first was the introduction of tension-free
      hernia repair by Liechtenstein in 1989 and the second was the application of
      laparoscopic surgery to the treatment of inguinal hernia in the early 1990s. The
      purposes of this study were to assess the safety and effectiveness of
      laparoscopic totally extraperitoneal (TEP) repair and to discuss the technical
      changes that we faced on the basis of our accumulative experience. METHODS:
      Patients who underwent an elective inguinal hernia repair at the Department of
      Abdominal Surgery at the Institute of Laparoscopic Surgery (ILS), Bordeaux,
      between June 1990 and May 2005 were enrolled retrospectively in this study.
      Patient demographic data, operative and postoperative course, and outpatient
      follow-up were studied. RESULTS: A total of 3,100 hernia repairs were included in
      the study. The majority of the hernias were repaired by TEP technique; the repair
      was done by transabdominal preperitoneal (TAPP) repair in only 3%. Eleven percent
      of the hernias were recurrences after conventional repair. Mean operative time
      was 17 min in unilateral hernia and 24 min in bilateral hernia. There were 36
      hernias (1.2%) that required conversion: 12 hernias were converted to open
      anterior Liechtenstein and 24 to laparoscopic TAPP technique. The incidence of
      intraoperative complications was low. Most of the patients were discharged at the
      second day of the surgery. The overall postoperative morbidity rate was 2.2%. The
      incidence of recurrence rate was 0.35%. The recurrence rate for the first 200
      repairs was 2.5%, but it decreased to 0.47% for the subsequent 1,254 hernia
      repairs CONCLUSION: According to our experience, in the hands of experienced
      laparoscopic surgeons, laparoscopic hernia repair seems to be the favored
      approach for most types of inguinal hernias. TEP is preferred over TAPP as the
      peritoneum is not violated and there are fewer intra-abdominal complications.

PMID- 18810549
TI  - Seasonal and sex-specific mRNA levels of key endocrine genes in adult yellow
      perch (Perca flavescens) from Lake Erie.
AB  - To better understand the endocrine mechanisms that underlie sexually dimorphic
      growth (females grow faster) in yellow perch (Perca flavescens), real-time
      quantitative polymerase chain reaction (qPCR) was used to measure pituitary,
      liver, and ovary mRNA levels of genes related to growth and reproduction-sex in
      this species. Adult perch were collected from Lake Erie and body mass, age,
      gonadosomatic index (I (G)), hepatosomatic index (I (H)), and gene expression for
      growth hormone (GH), prolactin, somatolactin, insulin-like growth factor Ib (IGF
      Ib), estrogen receptor alpha (esr1), estrogen receptor betaa (esr2a), and
      aromatase (cyp19a1a) were measured. Females had higher body mass, I (H), and
      liver esr1 mRNA level than males, while males had higher liver IGF-Ib, liver
      esr2a, and liver cyp19a1a mRNA levels. In both sexes, season had a significant
      effect on GH and liver IGF-Ib mRNAs with higher levels occurring in spring, which
      also corresponded with higher liver cyp19a1a mRNA levels. For females, I (G),
      liver esr1, and ovary cyp19a1a mRNA levels were higher in autumn than the spring,
      and ovary cyp19a1a mRNA levels showed a significant negative correlation with
      pituitary GH and liver IGF-Ib mRNA levels. The most significant (p </= 0.001)
      relationships across the parameters measured were positive correlations between
      liver IGF-Ib and esr2a mRNA levels and liver IGF-Ib and cyp19a1a mRNA levels.
      This study shows significant effects of season and sex on adult yellow perch
      endocrine physiology.

PMID- 18810550
TI  - Perceived vaccination status in ecotourists and risks of anthropozoonoses.
AB  - Anthropozoonotic (human to nonhuman animal) transmission of infectious disease
      poses a significant threat to wildlife. A large proportion of travelers to
      tropical regions are not protected against vaccine-preventable illnesses, and a
      majority of these travelers demonstrate poor recall of actual vaccination status.
      Here we characterize self-perceived vaccination status among a large sample of
      ecotourists at the Sepilok Orangutan Rehabilitation Centre, Sabah, Malaysia.
      Despite their recognized travel itinerary to view endangered animals, tourists at
      wildlife sanctuaries are not adequately protected against vaccine-preventable
      illnesses. Of 633 surveys, over half reported being currently vaccinated against
      tuberculosis, hepatitis A, hepatitis B, polio, and measles. Fewer participants
      reported current vaccination status for influenza, rabies, and chickenpox.
      Despite the fact that the majority of visitors to Sepilok are from temperate
      regions where influenza is relatively more prevalent, 67.1% of those surveyed
      with medical-related occupations reported not being currently vaccinated for
      influenza. Ecotourists concerned about environmental protection are themselves
      largely unaware of their potential contribution to the spread of diseases to
      animals. The risks of negatively affecting animal populations must be
      communicated to all concerned parties, and this may begin by urging travelers to
      examine their actual vaccination status, particularly as the ecotourism industry
      continues its rapid expansion, and is seen increasingly as a possible tool to
      save great ape populations from extinction.

PMID- 18810551
TI  - Aposematism in Archips cerasivoranus not linked to the sequestration of host
      derived cyanide.
AB  - This study addressed the question of how caterpillars of Archips cerasivoranus
      feeding upon Prunus virginiana cope with the cyanogenic compounds of their food.
      Analysis by ion chromatography showed that young and aged leaves of P. virginiana
      consumed by the caterpillars during spring have hydrogen cyanide potentials (HCN
      ps) of 2,473 +/- 130 ppm and 1,058 +/- 98 ppm, respectively. Although less than
      3% of the cyanide released as the caterpillars feed escapes into the atmosphere,
      the larva's bright-yellow aposematic coloration and conspicuous activity can not
      be attributed to the sequestration of cyanide. Only six of 25 samples of the
      caterpillars' defensive regurgitants collected from 12 field colonies contained
      cyanide (17.6 +/- 6.54 ppm), less than 5% of the quantity previously reported to
      occur in the regurgitant of the tent caterpillar M. americanum. Only seven of 13
      caterpillars assayed had detectable quantities of cyanide in their bodies (3.9 +/
      0.9 ppm). The fecal pellets that encase the cocoon contained no cyanide, nor did
      the frass that litters the leaf shelters. The small quantities of cyanide that
      occur in the caterpillar compared to the HCN-p of ingested plant material appear
      attributable to paced bouts of feeding and the maintenance of a highly alkaline
      foregut that inhibits cyanogenesis.

PMID- 18810552
TI  - Effects of plant vascular architecture on aboveground-belowground-induced
      responses to foliar and root herbivores on Nicotiana tabacum.
AB  - Herbivores induce systemic changes in plant traits, and the strength of these
      induced responses is often associated with the degree of vascular connectivity
      that links damaged and undamaged plant tissues. Although this phenomenon is known
      to occur aboveground in leaves, it is unknown whether or not leaf-root induction
      similarly follows the vascular architecture of plants. To test for this
      possibility, we manipulated foliar and root herbivory on tobacco (Nicotiana
      tabacum) by the leaf-chewing insect Spodoptera exigua and the root-galling
      nematode Meloidogyne incognita. Subsequent changes in secondary chemistry
      (alkaloids and phenolics) were measured in leaves and roots that were
      orthostichous (vertically aligned) and nonorthostichous (opposite) from the
      herbivore-damaged tissues. Aboveground caterpillar herbivory elicited stronger
      secondary chemical responses in orthostichous compared with nonorthostichous
      plant tissues, although the magnitude of this difference was greater in leaves
      than roots. However, belowground nematode herbivory did not affect the secondary
      chemistry of tobacco leaves, despite inducing strong local responses in roots.
      Thus, plant vascular architecture can mediate the magnitude of systemic induction
      in roots as well as in leaves, with stronger responses in tissues that are more
      closely aligned. As a result, herbivores that co-occur on the same sector of
      plant (both aboveground and belowground) may be more likely to affect one another
      via induced responses than herbivores that occur on plant tissues sharing fewer
      resources.

PMID- 18810554
TI  - Migratory polyarthritis as a paraneoplastic syndrome.
AB  - Carcinomatous polyarthritis (CP) is a rare paraneoplastic disorder that has been
      associated with a variety of solid tumors. It presents in a similar manner to
      other polyarticular disorders and often precedes detection of the underlying
      malignancy, making recognition critical. CP responds to the treatment of the
      neoplastic process. We present a patient who initially presented with asymmetric
      inflammatory polyarthritis who was later diagnosed with bronchogenic carcinoma.
      Following the case report we present our learning objectives, which include the
      differential diagnosis of inflammatory polyarthritis, diagnostic approach to CP,
      and features that distinguish it from other more common causes of polyarthritis.
      We conclude with a brief discussion of the pathophysiology and management of CP.

PMID- 18810555
TI  - Loss of health insurance among non-elderly adults in Medicaid.
AB  - BACKGROUND: Major policy efforts to expand health coverage to the uninsured are
      under consideration. Drop-out among children in Medicaid--due to annual renewal
      requirements--is well-documented, but the recent extent of this problem among non
      elderly adults is unknown. OBJECTIVE: To estimate the loss of health insurance
      over time among adults in Medicaid and identify risk factors for drop-out.
      DESIGN: Survival analysis of Medicaid enrollment, using Kaplan-Meier curves and
      Cox proportional-hazards regression. Data are from the nationally representative
      Medical Expenditure Panel Survey, 2000-2004. The sample consists of non-elderly
      adults (n = 4,992) and children (n = 8,559) in Medicaid. Insurance status after
      12 months was measured for all individuals enrolled in Medicaid at the survey's
      outset. A survival analysis of disenrollment was then conducted for newly
      enrolled individuals. RESULTS: Nationwide, 2 million adults leave Medicaid and
      become uninsured annually. Disenrollment was significantly higher among adults
      than children (hazard ratio 1.75, 95% CI 1.65-1.86). Respectively, 20%, 43%, and
      55% of adults disenrolled within 6, 12, and 23 months of initial enrollment. Lost
      eligibility explained a small portion of disenrollment. Six months after
      disenrolling, 17% had reenrolled in Medicaid, 34% had other insurance, and 49%
      were uninsured. Men, younger adults, and Hispanics were more likely to drop out;
      those in Medicaid managed care or with disabilities were less likely. Overall
      health status and diseases, such as diabetes, heart disease, and depression, had
      no effect on drop-out. CONCLUSIONS: Drop-out from Medicaid is a major problem
      among adults--even among those with chronic diseases--and contributes to the
      presence of millions of uninsured Americans. Policy efforts to expand health
      coverage must address poor Medicaid retention. Clinicians should be aware of this
      issue when caring for non-elderly adults in Medicaid.

PMID- 18810556
TI  - Elevated granulocyte colony-stimulating factor, non-infectious leukocytosis and
      fevers in a patient with multiple myeloma.
AB  - BACKGROUND: We report the case of a 56-year-old male with multiple myeloma in
      whom recurrent fevers and leukocytosis delayed potentially effective chemotherapy
      due to concern for active infection. DESIGN AND MEASUREMENTS: A thorough
      infectious workup, including CT and PET scans, was negative. The patient was
      eventually found to have an elevated serum granulocyte colony-stimulating factor
      (G-CSF) of 113 pg/ml (normal range 0.0 - 39.1 pg/ml), which was likely the cause
      of his persistent leukocytosis and fevers. Multiagent chemotherapy was initiated,
      and the fevers resolved in the next 4 days. RESULTS: Leukocyte concentrations
      trended down after initiation of chemotherapy, but it is uncertain how much of
      the decline was attributable to immunosuppression. CONCLUSION: We report this
      well-documented case to demonstrate that G-CSF production should be considered as
      a cause of unexplained fever and leukocytosis in patients with multiple myeloma
      to prevent inappropriate and delayed definitive diagnosis and treatment.

PMID- 18810557
TI  - Patients with multiple chronic conditions do not receive lower quality of
      preventive care.
AB  - BACKGROUND: The implications of measuring and rewarding performance for patients
      with multiple chronic conditions have not been explored empirically. OBJECTIVE:
      To examine whether the number of chronic conditions was associated with patient's
      receipt of recommended preventive care. METHODS: We evaluated the association
      between the likelihood of receiving recommended preventive care and the number of
      chronic conditions in the diabetic population by analyzing the 2003 Medical
      Expenditure Panel Survey using logistic regression. Demographic characteristics
      and the number of chronic conditions were compared using chi(2) tests. OUTCOME
      MEASURES: Hemoglobin A1C test and diabetic eye exam. RESULTS: In 2003,
      approximately 14.2 million non-institutionalized Americans had diabetes and 23%
      of them had five or more chronic conditions besides diabetes. Those patients were
      67% (p < 0.05) and 50% (p < 0.001) more likely to receive hemoglobin A1C test and
      eye exams compared with diabetic patients with no additional chronic conditions.
      After adjusting for the number of office-based physician visits, a larger number
      of chronic conditions did not significantly affect the likelihood of receiving
      recommended care. Diabetic patients with more chronic conditions had more
      frequent office-based physician visits (p < 0.0001), and patients with 11 or more
      annual office-based physician visits were 43% (p < 0.05) and 40% (p < 0.01) more
      likely to receive hemoglobin A1C test and eye exam, respectively, compared with
      diabetic patients who had less than two office-based physician visits.
      CONCLUSIONS: Diabetic patients with more chronic conditions may receive better
      quality of preventive care, partly due to their higher number of office-based
      physician visits.

PMID- 18810558
TI  - Superior mesenteric artery syndrome: diagnosis and treatment strategies.
AB  - INTRODUCTION: Superior mesenteric artery (SMA) syndrome is an unusual cause of
      vomiting and weight loss resulting from the compression of the third part of the
      duodenum by the SMA. Various medical and psychiatric conditions may result in the
      initial rapid weight loss which causes narrowing of the aortomesenteric angle.
      The vomiting and obstructive syndrome is then self-perpetuated regardless of the
      initiating factors. The young age and nonspecific symptoms often lead to a delay
      in diagnosis. DISCUSSION: A series of eight cases is presented reviewing the
      presentation, investigations, surgical treatment by division of duodenum and
      duodenojejunostomy, and outcomes. CONCLUSION: SMA syndrome is a well-described
      entity which must be considered as a cause of vomiting associated with
      significant weight loss in young adults. Surgical treatment should be allied with
      psychological assessment to treat any underlying psychosocial abnormality.

PMID- 18810559
TI  - Zenker's diverticula: feasibility of a tailored approach based on diverticulum
      size.
AB  - BACKGROUND: Zenker's diverticula (ZD) can be treated by transoral
      diverticulostomy or open surgery (upper esophageal sphincter myotomy and
      diverticulectomy or diverticulopexy). The aim of this study was to compare the
      effectiveness of a minimally invasive (group A) versus a traditional open
      surgical approach (group B) in the treatment of ZD. MATERIAL AND METHODS: Between
      1993 and September 2007, 128 ZD patients underwent transoral diverticulostomy (n
      = 51) or cricopharyngeal myotomy and diverticulectomy or diverticulopexy (n =
      77). All patients were evaluated for symptoms using a detailed questionnaire.
      Manometry recorded upper esophageal sphincter (UES) pressure, relaxations, and
      intrabolus pharyngeal pressure. The size of the pouch was measured on the barium
      swallow. The choice of treatment was based on the size of the diverticulum and
      the patients' preference. Long-term follow-up data were available for 121/128
      (94.5%) patients with a median follow-up of 40 months (interquartile range, 17
      83). RESULTS: Mortality was nil. Three patients in group A (5.8%) and ten in
      group B (13%) had postoperative complications (p = n.s.). Hospital stays were
      markedly shorter for patients after diverticulostomy (p < 0.01). Postoperative
      manometry showed a reduction in UES pressure, improved UES relaxation, and lower
      intrabolus pressure in both groups (p < 0.05). Four patients in the open surgery
      group (5.2%) complained of severe dysphagia after surgery (three of them required
      endoscopic dilations). In the transoral diverticulostomy group, 11 patients
      (21.5%) required additional septal reduction (n = 8) or a surgical myotomy (n =
      3) for persistent symptoms (p < 0.01); nine of these 11 patients had a ZD < or =
      3 cm in size. After primary and complementary treatments, symptoms disappeared or
      improved significantly at long-term follow-up in 93.5% of patients in group A and
      96% of those in group B. CONCLUSION: Diverticulostomy is safe, quick, and
      effective for most patients with medium-sized ZD, but open surgery offers better
      long-term results as a primary treatment and should be recommended for younger,
      healthy patients, especially those with small diverticula. Small ZD may represent
      a formal contraindication to the transoral approach because an excessively short
      septum prevents a complete division of the sphincter fibers.

PMID- 18810560
TI  - Pyogenic complications of Crohn's disease, evaluation, and management.
AB  - The principal by which treatment of pyogenic complications anorectal disease is
      guided should rely heavily on small procedure with medical management of rectal
      disease and limitation of proctectomy. Management of pyogenic complications of
      abdominal Crohn's by an elective approach after percutanea drainage of abscess
      and nutritional repletion should prevent long term complication even when its
      patient is receiving immune suppressive therapy.

PMID- 18810561
TI  - Recurrence of anal adenocarcinoma after local excision and adjuvant
      chemoradiation therapy: report of a case and review of the literature.
AB  - INTRODUCTION: Tumors arising from the anal canal are rare, comprising 1.5% of all
      gastrointestinal tumors in the USA. The vast majority of these anal cancers are
      epidermoid (cloacogenic/basaloid and squamous cell carcinomas), while
      adenocarcinomas reportedly occur 5% to 19% of the time. Because of its rarity,
      reports about anal adenocarcinoma are limited to small retrospective studies and
      case reports. Moreover, no series has directly compared outcomes between patients
      undergoing the various available treatment options, making it difficult to
      determine the optimal treatment for this aggressive cancer. Current management of
      this cancer remains controversial, with some authors believing abdominoperineal
      resection with permanent colostomy should be considered the standard treatment.
      Others propose that combined chemoradiation be adopted as a possible treatment in
      certain patients. CASE PRESENTATION: We describe a case of recurrent anal
      adenocarcinoma after conservative management with local excision and adjuvant
      chemoradiation therapy.

PMID- 18810562
TI  - Correction of glycogenosis type 2 by muscle-specific lentiviral vector.
AB  - Glycogen storage disease type II (GSDII) or Pompe disease is an inherited disease
      of glycogen metabolism caused by a lack of functional lysosomal acid alpha
      glucosidase (GAA). Affected individuals store glycogen in lysosomes resulting in
      fatal hypertrophic cardiomyopathy and respiratory failure in the most severe
      form. We investigated for the first time the use of lentiviral vectors to correct
      the GSDII phenotype in human and murine GAA-deficient cells. Fibroblasts from
      infantile and adult GSDII patients were efficiently transduced by a GAA
      expressing lentiviral vector placed under the control of the strong MND promoter,
      leading to a complete restoration of enzymatic activity. We also developed a
      muscle-specific lentiviral vector based on the synthetic C5-12 promoter and
      tested it on deficient myogenic satellite cells derived from a GSDII mouse model.
      GAA was expressed as a correctly processed protein allowing a complete enzymatic
      and metabolic correction in myoblasts and differentiated myotubes, as well as a
      significant mannose-6-phosphate (M6P)-dependent secretion reuptake by naive
      cells. Transduced cells showed lysosomal glycogen clearance, as demonstrated by
      electron microscopy. These results form the basis for a therapeutic approach of
      GSDII using lentiviral vector-mediated gene transfer into muscle stem cells.

PMID- 18810563
TI  - Matrix-coated transwell-cultured TM4 sertoli cell testosterone-regulated gene
      expression mimics in vivo expression.
AB  - In vitro culture systems are needed to mimic in vivo epithelial cell environments
      for identifying cell signaling, gene expressions, and molecular mechanisms. One
      such system is matrix-coated transwell cultures. However, no data exist on
      culturing Sertoli cells in this manner with respect to testosterone-regulated
      gene expression. Because the TM4 mouse Sertoli-like cell line expresses androgen
      receptor, our objective was to determine if testosterone treatment added to the
      bottom chamber of a matrix-coated transwell system induces some gene expressions
      found in Sertoli cells in vivo. After serum starvation, transwell-cultured TM4
      cells were treated with testosterone or left untreated for 24 h. Microarray
      analyses initially identified differentially expressed genes either induced or
      repressed by testosterone treatment. By Northern blot analyses, Pem mRNA, a
      frequently used marker of Sertoli cell testosterone responsiveness, was induced.
      Proteins of the transcripts induced by testosterone in the in vitro system were
      immunolocalized to Sertoli cells in testosterone-dependent stages of
      spermatogenesis in mouse testes. By immunohistochemistry analyses of sectioned
      mouse testes, gene expression induced by testosterone in transwell-cultured TM4
      cells, profilin as well as secreted protein acidic and rich in cysteines (SPARC)
      are localized to Sertoli cells in testosterone-dependent stages of
      spermatogenesis. Findings include localizations of SPARC and profilin, as well as
      an apparent germ cell communication required for translation of Pem mRNA in
      Sertoli cells. Taken together, results of these studies suggest that this TM4
      transwell-culture system could be used to study these testosterone-regulated
      Sertoli gene expressions in vitro.

PMID- 18810564
TI  - Changes of the metabolism of the colon cancer cell line SW-480 under serum-free
      and serum-reduced growth conditions.
AB  - Serum of animal origin, like foetal calf serum (FCS), is used as a standard
      supplement for media to cultivate mammalian cells, mostly due to its growth
      supporting properties. Unfortunately, animal serum has many disadvantages like
      the risk of contamination, high costs, fluctuations within the composition of
      different batches and the high amount of foetuses, which have to be harvested. To
      avoid all this, it is necessary to provide alternatives, which combine as many
      positive properties of the animal serum as possible but do not influence the
      cellular metabolism negatively. Today, several serum-free complete media as well
      as serum substitutes are commercially available. In the present study, a serum
      substitute, a serum-reduced medium and a serum-free medium were evaluated
      concerning their influence on the metabolism on the colon cancer cell line SW
      480. The evaluation of morphological changes of the cells was done by microscopic
      analysis whereas differences in the volatile metabolome were analysed by solid
      phase micro extraction (SPME) followed by gas chromatography/mass spectrometry
      (GC/MS).

PMID- 18810565
TI  - Cultured trout gill epithelia enriched in pavement cells or in mitochondria-rich
      cells provides insights into Na+ and Ca 2+ transport.
AB  - The lack of a suitable flat epithelial preparation isolated directly from the
      freshwater fish gill has led, in recent years, to the development of cultured
      gill epithelia on semipermeable supports. To date, their minimal capacity to
      actively transport ions has limited their utility as ionoregulatory models. The
      current study describes a new method of culturing gill epithelia consisting
      either of an enriched population of pavement (PV) cells or a mixed population of
      PV cells and mitochondria-rich (MR) cells from the gills of adult rainbow trout.
      Although the cell culture approach is similar to the double-seeded insert (DSI)
      technique described previously, it makes use of Percoll density centrifugation to
      first separate populations of PV and MR cells, which are then seeded on cell
      culture supports in varying proportions on successive days so as to produce
      preparations enriched in one or the other cell types. Based on rhodamine
      staining, the MR cell-rich epithelia exhibited a threefold higher enrichment of
      MR cells compared to traditional DSI preparations. In general, MR cell-rich
      epithelia developed extremely high transepithelial resistances (TER; >30 kOmega
      cm(2)) and positive transepithelial potentials (TEP) under symmetrical conditions
      (i.e., L15 medium on both apical and basolateral sides). Apical exposure of cell
      cultures to freshwater reduced TER and produced a negative TEP in all the
      epithelial preparations, although MR cell-rich epithelia maintained relatively
      high TER and negative TEP for over 2 d under these asymmetrical conditions.
      Measurement of unidirectional Na(+) fluxes and application of the Ussing flux
      ratio criterion demonstrated active Na(+) uptake in PV cell-rich and MR cell-rich
      epithelia under both symmetrical and asymmetrical conditions. In comparison,
      Ca(2+) uptake and Na(+)/K(+)-ATPase activity were significantly elevated in MR
      cell-rich preparations relative to the traditional DSI or PV cell-rich cultures
      under symmetrical conditions. This new methodology enhances our ability to tailor
      cultured gill epithelia on semipermeable supports with different proportions of
      PV cells and MR cells, thereby illuminating the ionoregulatory functions of the
      two cell types.

PMID- 18810566
TI  - Effect of mood and eating disorders on the short-term outcome of laparoscopic
      Roux-en-Y gastric bypass.
AB  - BACKGROUND: We examined whether patients with a history of mood and eating
      disorders (MED) had less weight loss and poorer treatment compliance after
      laparoscopic Roux-en-Y gastric bypass (LRYGBP) than patients with a history of
      either mood (MD) or eating disorders (ED), or no history of mood or eating
      disorders (ND). METHODS: Consecutive LRYGBP patients (n = 196; 43.6 +/- 10.9
      years; BMI 47.2 +/- 7.4 kg/m(2); 83.2% female, 91.8% Caucasian) underwent a
      preoperative psychological evaluation. At 6 months post-surgery, body mass index
      (BMI), % excess weight loss (%EWL), hospital readmissions, and adherence to
      behavioral recommendations were assessed. RESULTS: Of the patients, 10.2% had
      MED, 36.7% had ED only, 24.0% had MD only, and 29.1% of patients had ND. MED
      patients fared worse than all other groups in dietary violations (p = 0.03),
      exercise habits (p = 0.05), and readmission rates (p = 0.06) but there were no
      group differences in either BMI change or %EWL. CONCLUSIONS: MED patients are at
      risk for poor treatment compliance following LRYGBP; however, they achieve
      similar weight losses 6 months postoperatively.

PMID- 18810567
TI  - Orthopaedic . radiology . pathology conference: Chronic multifocal chest and leg
      pain in a 34-year-old woman.

PMID- 18810568
TI  - Case report: The prone reduction of a sacroiliac disruption with a pelvic C
      clamp.
AB  - The pelvic C-clamp traditionally is reserved for the temporizing stabilization of
      posterior ring injuries and reportedly has assisted in closed reduction of
      sacroiliac diastases, for patients who are in the supine position. We report a
      patient with a severely displaced Zone II sacral fracture and associated
      acetabular fracture who initially underwent fixation of the acetabulum in the
      prone position. By using the pelvic C-clamp as a tool for successfully reducing
      the sacrum, definitive closed fixation of the pelvic wing subsequently was
      performed without having to reposition the patient. In this case report, we
      review the literature on this device and for alternative reduction maneuvers for
      disrupted sacral injuries. The C-clamp may be a useful adjunct in select cases to
      facilitate closed reduction of sacral or sacroiliac joint disruptions, as may
      particularly apply in cases of severe displacement or when a reduction is
      hampered by obesity.

PMID- 18810569
TI  - Femoral deformity correction in children and young adults using Taylor Spatial
      Frame.
AB  - The Taylor spatial frame (TSF) has been used commonly in children and young
      adults. Its use in the tibia is more extensively studied and applied than in the
      femur. We asked whether normal alignment can be achieved with accuracy during
      correction of femoral deformities while avoiding major complications in children
      and young adults. We retrospectively reviewed the clinical and radiographic
      records of 20 patients (22 limbs), ages 5.9 to 24.6 years, who underwent a TSF
      for femoral deformity. Etiology included a number of diagnoses of the pediatric
      age. Minimum followup was 4.5 months (mean, 15.7 months; range, 4.5-35 months).
      The mean time in frame was 6.2 months (range, 2.6-19 months). Frontal and
      sagittal plane deformities were corrected to within normal values. A mean limb
      lengthening of 4.9 cm (range, 1.5-9 cm) was performed in eight femora in seven of
      which the limb length discrepancy was a secondary concern. External fixation
      index in the lengthening subgroup was 2.2 months/cm. The 15 complications in 13
      limbs included pin tract infection, knee stiffness, delayed union, skin
      irritation, and posterior knee subluxation. No complications occurred in nine
      limbs. Computer-assisted femoral deformity correction with six-axis deformity
      analysis and the TSF is an accurate and safe technique in children and young
      adults. LEVEL OF EVIDENCE: Level IV, therapeutic study. See the Guidelines for
      Authors for a complete description of levels of evidence.

PMID- 18810570
TI  - The Chitranjan Ranawat Award: functional outcome after total knee replacement
      varies with patient attributes.
AB  - Total knee replacement effectively relieves arthritis pain but improvement in
      physical function varies. A clearer understanding of the patient attributes
      associated with differing levels of functional gain after TKR is critical to
      surgical decision making. We reviewed 8050 primary, unilateral TKR patients
      enrolled in a prospective registry between 2000 and 2005 who had complete data.
      We evaluated associations between 12-month function (SF12/PCS) and preoperative
      gender, age, BMI, emotional health (MCS), knee diagnosis, quadriceps strength,
      and physical function (PCS). More than 98% of patients reported pain relief (KS
      pain score). At 12 months, mean PCS gain was 13.6 points, but the distribution
      was bimodal. The mean gain in PCS in the 63% of patients with greater improvement
      was 21 (SD = 7), and 4.1 (SD = 7) in the remaining 37%. Increased likelihood of
      poor functional gain was associated with older age, body mass index (BMI) over
      40, lower MCS, and poor quadriceps strength. While two-thirds of patients
      reported functional gain well above national average at 12 months post-TKR, 37%
      reported limited functional improvement. Further understanding of the patient
      attributes associated with limited improvement will guide the design of
      innovative strategies to improve functional outcomes. LEVEL OF EVIDENCE: Level
      II, prognostic study. See the Guidelines for Authors for a complete description
      of levels of evidence.

PMID- 18810571
TI  - High prevalence of low bone density in young Iranian healthy individuals.
AB  - With the increasing life expectancy, osteoporosis is becoming a major worldwide
      health problem, more particularly in the Middle East region. Bone mineral density
      (BMD) of the hip, lumbar spine, and forearm was measured by dual X-ray
      absorptiometry (Lunar) in 2085 (25% men, 75% women) healthy Iranian subjects aged
      20-88 yr. The prevalence of osteoporosis and osteopenia in at least one measured
      site in subjects aged 50 yr and older were 36.1% and 43.9% in women, and 24.5%
      and 70.8% in men, respectively. Among subjects younger than 50 yr, 49.6% of women
      and 59.6% of men had low bone mass, respectively. In addition, more than one
      third of subjects showed discordance between different sites of measurement. The
      high incidence of low bone density in young ages requires our proper attention
      and planning for prevention. Measurement of BMD in all three sites seems
      necessary and clinicians should look for possible causes of discordance between
      different sites of measurement and develop an appropriate strategy approaching to
      these patients.

PMID- 18810573
TI  - Cleavage sites of the "P3 region" in the nonstructural polyprotein precursor of a
      dicistrovirus.
AB  - Plautia stali intestine virus (PSIV) is a member of the family Dicistroviridae.
      Dicistroviruses, like picornaviruses, are thought to encode a 3C-like protease;
      however, the cleavage sites of dicistroviral nonstructural polyprotein precursors
      are unknown except for those in genome-linked virus protein (VPg) regions. We
      expressed part of the PSIV polyprotein in Escherichia coli and detected
      autoprocessed viral proteins. N-terminal sequence analysis of the autoprocessed
      proteins showed that Q/GWLSW and Q/NGVFD in the PSIV sequence correspond to 2C/3A
      and 3C/3D cleavage sites in picornaviruses. Alignments of deduced amino acid
      sequences of the "P3 region" suggest that these cleavage sites can be predicted.

PMID- 18810572
TI  - Controversies in the management of tongue base cancer.
AB  - BACKGROUND: Tongue base cancer is one of the most lethal head and neck cancers.
      There is considerable controversy in the management of this disease with wide
      variation of opinion within the literature. METHODS: We discuss the presentation,
      diagnostic and therapeutic strategies which exist in the literature. Articles
      were reviewed from 1970 to 2007 within the Medline, Pubmed and Cochrane
      libraries. CONCLUSIONS: Smokers with a history of persistent unilateral neck
      pain, even in the absence of clinical signs warrant MRI neck imaging. Tongue base
      cancer organ preservation therapeutic strategies, radiation and concomitant
      platinum based chemotherapy, currently optimise oncologic and quality of life
      outcomes.

PMID- 18810574
TI  - ER-to-Golgi transport by COPII vesicles in Arabidopsis involves a ribosome
      excluding scaffold that is transferred with the vesicles to the Golgi matrix.
AB  - Plant Golgi stacks are mobile organelles that can travel along actin filaments.
      How COPII (coat complex II) vesicles are transferred from endoplasmic reticulum
      (ER) export sites to the moving Golgi stacks is not understood. We have examined
      COPII vesicle transfer in high-pressure frozen/freeze-substituted plant cells by
      electron tomography. Formation of each COPII vesicle is accompanied by the
      assembly of a ribosome-excluding scaffold layer that extends approximately 40 nm
      beyond the COPII coat. These COPII scaffolds can attach to the cis-side of the
      Golgi matrix, and the COPII vesicles are then transferred to the Golgi together
      with their scaffolds. When Atp115-GFP, a green fluorescent protein (GFP) fusion
      protein of an Arabidopsis thaliana homolog of the COPII vesicle-tethering factor
      p115, was expressed, the GFP localized to the COPII scaffold and to the cis-side
      of the Golgi matrix. Time-lapse imaging of Golgi stacks in live root meristem
      cells demonstrated that the Golgi stacks alternate between phases of fast,
      linear, saltatory movements (0.9-1.25 microm/s) and slower, wiggling motions
      (<0.4 microm/s). In root meristem cells, approximately 70% of the Golgi stacks
      were connected to an ER export site via a COPII scaffold, and these stacks
      possessed threefold more COPII vesicles than the Golgi not associated with the
      ER; in columella cells, only 15% of Golgi stacks were located in the vicinity of
      the ER. We postulate that the COPII scaffold first binds to and then fuses with
      the cis-side of the Golgi matrix, transferring its enclosed COPII vesicle to the
      cis-Golgi.

PMID- 18810576
TI  - Current topics and perspectives on the use of aromatase inhibitors in the
      treatment of breast cancer.
AB  - Tamoxifen has played a central role in endocrine therapy for hormone-responsive
      breast cancer. Results of recent clinical trials have, however, clearly shown
      that third-generation aromatase inhibitors (AIs), such as anastrozole, letrozole
      and exemestane, are superior to tamoxifen in the treatment of postmenopausal
      patients with metastatic breast cancer, in an adjuvant setting and for early
      breast cancer. Many studies have been published that describe new results from
      clinical trials and how they fundamentally prove the efficacy of AIs. There are,
      however, still some unresolved issues concerning the applications of AIs, such as
      the optimal duration of the therapy, the optimal regimens (initial, adjuvant or
      switching from tamoxifen to AI), and combination with LH-RH agonists for
      premenopausal woman. These issues are discussed in this review. Additionally,
      further possibilities for the application of AIs, for example in combination
      therapy with pure antiestrogen aimed at complete estrogen blockade and in
      combination with new biological agents, as well as the pharmacogenomics of AIs
      will be discussed.

PMID- 18810575
TI  - Assessment of anti-inflammatory and hepatoprotective potency of Polyalthia
      longifolia var. pendula leaf in Wistar albino rats.
AB  - The objective of the present study was to screen various solvent extracts of
      Polyalthia longifolia var. pendula (Annonaceae) leaf for anti-inflammatory
      activity and to evaluate the anti-inflammatory and hepatoprotective potency of
      the potent solvent extract. Successive extraction was performed with six
      different solvents, viz. petroleum ether, hexane, toluene, chloroform, acetone
      and methanol. Toluene, chloroform, acetone and methanol were used in acute
      inflammatory studies; the results revealed methanol as most potent extract. Hence
      three concentrations of methanolic extract (300, 600, 900 mg/kg) were used to
      evaluate its potential as an anti-inflammatory and hepatoprotective agent.
      Diclofenac sodium was used as the toxicant in hepatoprotective studies, in which
      various serum biochemical parameters and liver glycogen were assessed. The three
      concentrations of methanol showed anti-inflammatory activity comparable to that
      of the control (Diclofenac sodium). All the serum biochemical parameters studied
      revealed the hepatoprotective nature of the methanol extract, but a concentration
      effect was not observed. The results indicated that the methanolic extract of
      Polyalthia longifolia var. pendula leaf possesses significant anti-inflammatory
      and hepatoprotective activity. However, the appropriate effective concentration
      needs to be determined.

PMID- 18810577
TI  - Carotid intima-media thickness in pre- and postmenopausal women with suspected
      coronary artery disease.
AB  - Carotid intima-media thickness (CIMT) is an early marker of coronary artery
      disease (CAD). This study aimed to evaluate CIMT value for CAD prediction in pre
      and postmenopausal women referred for coronary angiography with angina-like
      symptoms and a positive result of the treadmill test. The study comprised 321
      women referred for coronary angiography with symptoms suggesting CAD. Carotid
      intima-media thickness was measured in common, bifurcation, and internal carotid
      artery, and expressed as the mean maximum value. Coronary angiography showed
      coronary stenosis > or = 50% in 211 (65.7%) women, including 27 with regular
      menses (47.3 +/- 3.4 years) and 184 postmenopausal (65.8 +/- 7.2 years). Normal
      coronary arteries were found in 110 women: 17 (47.3 +/- 4.9 years) with regular
      menses and 93 postmenopausal (64.3 +/- 6.5 years). The highest CIMT values were
      found in postmenopausal CAD women (1.360 +/- 0.32 mm), as compared to
      premenopausal with CAD (1.178 +/- 0.36 mm, P = 0.005), pre- (0.860 +/- 0.23 mm, P
      < 0.001) and postmenopausal (1.022 +/- 0.30 mm, P < 0.001) women without CAD.
      Carotid intima-media thickness (P < 0.001), hyperlipidemia (P = 0.018), and
      myocardial infarction (P < 0.001), but not menopause itself or the number of
      years since menses cessation, were found to be independent CAD predictors. By
      receiver operating characteristic calculation, the mean maximum CIMT cut-off
      values discriminating CAD were lower in premenopausal (> or = 0.933 mm) than in
      postmenopausal women (> or = 1.075 mm; P < 0.05) resulting in similar sensitivity
      (85.2% and 82.6%) and specificity (70.6% and 69.9%). Carotid intima-media
      thickness is a strong CAD predictor in both pre- and postmenopausal women, in
      contrast to the menopausal status.

PMID- 18810578
TI  - Acute myocardial infarction as a systemic prothrombotic condition evidenced by
      increased von Willebrand factor protein over ADAMTS13 activity in coronary and
      systemic circulation.
AB  - The aim of the present study is to clarify the roles of circulating ADAMTS13 and
      von Willebrand factor (VWF) in the formation of coronary artery thrombi in acute
      myocardial infarction (AMI). Twenty-six AMI patients, 37 age-matched healthy
      controls, and 20 young controls were studied. Plasma ADAMTS13 activity and levels
      of VWF antigen (VWF: Ag) and unusually large VWF multimer (UL-VWFM) were measured
      in the femoral vein (FV), aortic root (Ao), and coronary sinus (Cs) immediately
      before percutaneous coronary intervention (PCI) during the acute phase of AMI, as
      well as 6 months later. During the acute phase of AMI, plasma levels of VWF: Ag
      were similar in FV, Ao, and Cs, and were higher than those of age-matched
      control. In contrast, ADAMTS13 activity in three sampling points in AMI patients
      was similar to that of age-matched controls. Thus, the ratio of VWF: Ag to
      ADAMTS13 activity in the acute phase of AMI was significantly higher in all three
      sampled sites than that of age-matched controls. In the chronic phase, plasma
      levels of VWF: Ag, ADAMTS13 activity, and the ratio of VWF: Ag to ADAMTS13
      activity were similar to those of age-matched controls. UL-VWFM was detected in
      the acute phase of AMI but not in the chronic phase. The present study showed
      that the plasma VWF: Ag levels are increased and ADAMTS13 activity is relatively
      decreased in both systemic and coronary circulation during the acute phase of
      AMI, suggesting that an imbalance between the enzyme and its substrate may play a
      role in the formation of occlusive thrombi in a coronary artery.

PMID- 18810579
TI  - Endothelial functional and structural impairment in patients with different
      degrees of coronary artery disease development.
AB  - Flow-mediated dilatation (FMD) and intima-media thickness (IMT) are noninvasive
      methods for patient evaluation. In this study we aimed to estimate the
      correlation between FMD and IMT in patients with different degree of coronary
      artery disease (CAD) development, and to explore their prognostic significance
      for the presence of angiographically significant coronary artery stenosis. We
      included 198 patients divided into five groups according to the degree of CAD
      development. All patients had FMD and IMT measured, 105 (53.03%) performed a
      Treadmill test in our clinic, and 146 (73.7%) underwent coronary arteriography
      (CAG). Patients with significant (> or = 50%) coronary artery stenosis had lower
      FMD and higher IMT values compared to patients without significant CAD: FMD:
      2.78% +/- 2.71% vs 8.24% +/- 5.16%, respectively, P < 0.001; IMT: 0.882 +/- 0.17
      mm vs 0.763 +/- 0.16 mm, respectively, P < 0.001. There existed a weak negative
      correlation between FMD and IMT (correlation coefficient: 0.242, P < 0.001),
      which was lost in subgroups and after controlling for the presence of significant
      CAD, number of diseased coronary arteries, and percent coronary artery stenosis.
      Analyzing the receiver operating characteristic curves we found that FMD values <
      or = 4.5% had 74% sensitivity, 77% specificity, positive predictive value (PPV)
      81.8%, and negative predictive value (NPV) 68%, and IMT values > or = 0.81 mm had
      sensitivity 71%, specificity 67%, PPV 76.1%, and NPV 63.1% for the presence of
      significant CAD. Patients with advanced CAD had lower FMD and higher IMT values
      compared to patients with minor changes. The correlation between FMD and IMT was
      weak and inconsistent. Both methods demonstrated an acceptable prognostic
      significance for the presence of significant CAD.

PMID- 18810580
TI  - Intraoperative behavior of arterial grafts in the elderly and the young: a
      flowmetric systematic analysis.
AB  - Extensive arterial grafting (Art-CABG) in the elderly is still questioned due to
      the reduced life expectancy and the supposed higher periprocedural risk. Reports
      further demonstrated accelerated atherosclerosis of arterial grafts in the
      elderly, with hampered short-term and long-term results. We reviewed our
      experience of patients undergoing Art-CABG between January 2003 and January 2007,
      divided into two groups: the elderly (238 patients > or = 70 years; Group A) and
      the young (195 patients < or = 60 years; Group B). Transit time flowmetric (TTF)
      maximum and mean flow, pulsatility index (PI), and graft flow reserve (GFR) were
      compared. Hospital outcome was analyzed. Hospital mortality, need for intra
      aortic balloon pump, troponin I, and echocardiographic segmental kinetics were
      comparable between the two groups (P = not significant [NS]). Stratifying
      patients for target vessels and type of arterial CABG, no differences in TTF
      results were recorded between the two groups either on-pump (P = NS) and off-pump
      (P = NS), both for the two internal mammary arteries (P = NS irrespective of the
      target vessel) and the radial artery conduits (P = NS irrespective of the target
      vessel). Although graft flow reserve was significantly recruited in all patients
      (P < 0.05 in young and elderly, either on-pump and off-pump, irrespective of the
      arterial conduit and the grafted vessel), GFR of all arterial grafts was
      comparable between elderly and young patients, either on-pump (P = NS) or off
      pump (P = NS). Art-CABG showed similar TTF results in elderly and young patients,
      regardless of the arterial conduit, target vessel, or surgical technique
      employed. These functional results supported the reported survival benefit of
      arterial revascularization in the elderly.

PMID- 18810581
TI  - Association of corrected QT dispersion with symptoms improvement in patients
      receiving cardiac resynchronization therapy.
AB  - Cardiac resynchronization therapy (CRT) is theoretically expected to affect
      repolarization as well as depolarization. We studied the effects of CRT on
      corrected QT (QTc) dispersion in association with symptomatic improvement. QTc
      dispersion was analyzed in 26 consecutive patients (67 +/- 6 years old, 18 men
      and 8 women) who underwent CRT. CRT responders and nonresponders were defined as
      patients showing and not showing > or = 1 class New York Heart Association
      symptomatic improvement 3 months after CRT, respectively. QTc interval, QRS
      width, and QTc dispersion were measured automatically from digital data using an
      analyzing system. There were 18 CRT responders and 8 nonresponders among the
      patients. CRT responders showed significantly larger QTc dispersion than CRT
      nonresponders before CRT (102 +/- 26 vs 40 +/- 12 ms, P < 0.01). A significant
      decrease in QTc dispersion by CRT was observed in responders (102 +/- 26 to 52 +/
      15 ms, P < 0.01). In contrast, QTc dispersion was not decreased by CRT in
      nonresponders (40 +/- 12 to 39 +/- 11 ms, not significant). The difference
      observed before CRT was thus abolished after CRT (52 +/- 15 vs 39 +/- 11 ms, not
      significant). Baseline values and changes in QRS width or QTc, as well as
      asynchrony of wall motion determined by tissue Doppler imaging, were not
      different between CRT responders and nonresponders before CRT. The present study
      with a small number of patients shows the potential utility of QTc dispersion for
      distinguishing CRT responders from CRT nonresponders before CRT, and warrants
      further study with a greater number of patients.

PMID- 18810582
TI  - Early use of beta-blockers attenuates systemic inflammatory response and lung
      oxygenation impairment after distal type acute aortic dissection.
AB  - We have reported that serum C-reactive protein (CRP) elevation is an independent
      predictor of lung oxygenation impairment (LOI) after distal type acute aortic
      dissection (AAD). Systemic activation of the inflammatory system after aortic
      injury may play a role in the development of LOI. The aim of this study is to
      clarify the effect of beta-blockers on systemic inflammation and the development
      of LOI after distal type AAD. A total of 49 patients, who were admitted with
      distal type AAD and treated conservatively, were examined. White blood cell (WBC)
      count, serum CRP level, and arterial blood gases were measured serially. Forty
      patients received beta-blocker treatment within 24 h of the onset, while 9
      patients received no beta-blocker treatment. Maximum WBC count, maximum CRP
      level, lowest PaO(2)/FiO(2) (P/F) ratio, and patient background were compared
      between the two groups. There was no difference between the groups according to
      age, sex, coronary risk factors, blood pressure, serum level of CRP, WBC count,
      and oxygenation index on admission. Beta-blocker treatment was associated with
      lower maximum WBC count (P = 0.0028) and lower maximum serum CRP level (P =
      0.0004). The minimum P/F ratio was higher in patients with beta-blocker treatment
      than in those without (P = 0.0076). Multivariate analysis revealed that
      administration of a beta-blocker was an independent negative determinant of LOI
      (P/F ratio < or = 200 mmHg). In conclusion, early use of beta-blockers prevented
      excessive inflammation and LOI after distal type AAD, suggesting a pleiotropic
      effect of beta-blockers on the inflammatory response after AAD.

PMID- 18810583
TI  - Association of the matrix metalloproteinase-3 (-439C/G) promoter polymorphism
      with Kawasaki disease in Korean children.
AB  - Kawasaki disease (KD) is a multisystemic vasculitis that often includes coronary
      artery involvement. The serum levels of matrix metalloproteinase (MMP)-3 and -9
      are significantly elevated in KD patients, and polymorphisms in the genes
      encoding MMP-3 and MMP-9 have been associated with the susceptibility, severity,
      and progression of atherosclerosis and aneurysm. However, the association between
      MMP-3 gene polymorphisms and development of aneurysm is somewhat controversial in
      a number of diseases. Ninety-seven children with KD and 194 children with
      congenital heart disease (CHD) were included in this study. Echocardiography was
      used to examine all children in the KD group for coronary artery aneurysm.
      Genotyping of the MMP-3 (-439C/G) promoter polymorphism was performed using the
      single-base extension method, and serum MMP-3 levels were estimated using the
      sandwich enzyme immunoassay method. There was no significant difference in MMP-3
      (-439C/G) genotypes between KD and control groups. There was no association
      between this MMP-3 polymorphism and development of coronary aneurysm in KD. Serum
      MMP-3 levels were significantly higher in KD patients compared to control
      subjects. Among the KD patients, serum MMP-3 levels were higher in children with
      genotypes CG+GG compared to the CC group, but this difference was not
      significant. Although further large-scale studies will be required to fully
      examine the relationship between MMP-3 gene polymorphisms and coronary artery
      lesions (CAL) in KD, the present findings suggest that while MMP-3 may play a
      role in the pathogenesis of KD, there is no apparent association between CAL and
      the MMP-3 (-439C/G) gene polymorphism in Korean children with KD.

PMID- 18810585
TI  - New ST-segment elevation caused by spontaneous recanalization of the left
      anterior descending coronary artery.
AB  - We report a rare case of a male patient with acute myocardial infarction, in whom
      spontaneous recanalization of an occlusive lesion in the left anterior descending
      artery produced new ST-segment elevation in the precordial leads, although the
      exact mechanism for this phenomenon is unclear.

PMID- 18810584
TI  - HFE mutations in heart disease.
AB  - Given the reported association of cardiac complications with hereditary
      hemochromatosis and the high carrier frequency of HFE gene mutations in the
      natural population, it seems reasonable that such mutations might appear more
      frequently than expected among symptomatic cardiac patients. Thus, H63D, C282Y,
      and S65C mutations and their possible associations were examined in 477 Caucasian
      males undergoing coronary angiography. Genotypes were analyzed for differences
      between ferritin and transferrin levels, coronary artery disease (CAD),
      cardiomyopathy (CM), and cardiovascular disease (CVD) mortality. No significant
      differences were found in ferritin levels between those with or without HFE
      mutations (C282Y P = 0.632, H63D P = 0.765, S65C P = 0.568, and HFE mutation P =
      0.568); however, there was a significant difference (P = 0.005) in mean
      transferrin levels between those with (252 microg/l) and without (275 microg/l)
      C282Y. No relationship between HFE mutations and CAD (C282Y, P = 0.402; H63D, P =
      0.112; S65C, P = 0.170) or CVD death (C282Y, P = 0.560; H63D, P = 0.682; S65C, P
      = 0.664) was demonstrated using logistic regression. However, an association
      between S65C and CM was found (odds ratio 4.4; 95% confidence interval 1.3-13.3,
      P = 0.018). This suggests that the S65C allele may contribute to the development
      of CM, but that these three HFE mutations do not appear to play a significant
      role in development of ischemic heart disease.

PMID- 18810586
TI  - Monoparesis due to spinal cord infarction associated with thoracoabdominal
      aneurysm.
AB  - We describe a case of acute monoparesis of a lower limb due to asymmetric spinal
      cord infarction in a patient with previously unrecognized thoracoabdominal
      aneurysm. The clinical course suggested that the likely reason for the spinal
      cord infarction was thromboembolism originating from the aneurysm's mural
      thrombi. This rare entity should be considered when managing patients with acute
      mono- or paraparesis who have a thoracoabdominal aneurysm with mural thrombi
      because interventions aimed at preventing further embolisms could be beneficial
      in these patients.

PMID- 18810587
TI  - Whole-heart coronary magnetic resonance angiography of double left anterior
      descending artery.
AB  - Double left anterior descending artery arising from the left and right coronary
      arteries is an extremely rare congenital coronary anomaly. We describe, for the
      first time, three-dimensional, whole-heart coronary magnetic resonance
      angiographic findings of double left anterior descending artery.

PMID- 18810588
TI  - A left ventricular lipoma diagnosed on three-dimensional electrocardiogram-gated
      cardiac computed tomography.
AB  - Cardiac lipomas are extremely rare primary benign cardiac tumors. We describe a
      patient with a chief complaint of ventricular tachycardia associated with a
      lipoma arising in the left ventricular myocardium. The cardiac lipoma was
      qualitatively evaluated and its location was accurately determined noninvasively
      with the use of three-dimensional images reconstructed from data acquired by
      electrocardiogram-gated cardiac computed tomography (CT). Our experience suggests
      that high-resolution three-dimensional CT imaging may facilitate the
      determination of strategies for surgical treatment.

PMID- 18810589
TI  - Protective effects of N-acetylcysteine and Ginkgo biloba extract on ischaemia
      reperfusion-induced hepatic DNA damage in rats.
AB  - Hepatic ischaemia-reperfusion injury is a serious problem that occurs during
      various surgical operations such as liver transplantation, surgical
      revascularization, and partial organ resection. Different pharmacological agents
      have been used for the protection of organ function and for extending the
      tolerable ischaemic interval after the ischaemic insult. We aimed to determine
      the presence of 8-hydroxydeoxyguanosine (8-OHdG) in the DNA from liver undergoing
      ischaemia-reperfusion, and also to evaluate the protective effects of N
      acetylcysteine (NAC) and EGb761 (Ginkgo biloba extract) against hepatic oxidative
      DNA damage. A total of 40 rats were divided into four groups of 10 animals each
      (sham-operation group, control group, NAC group, and EGb761 group). Oxidative
      damage to DNA was evaluated by measuring the increase in 8-OHdG formation in
      liver tissue and also the effects of NAC and EGb761 pretreatment. Hepatic
      ischaemia for 90 min followed by reperfusion caused a marked increase in tissue
      levels of 8-OHdG, thiobarbituric acid-reactive substance, serum ALT, AST and LDH
      activities compared to sham-operated group. Pretreatment with both NAC and EGb761
      clearly diminished 8-OHdG formation and lipid peroxidation. These findings
      suggest that antioxidant molecules such as NAC and EGb761 may be useful in
      preventing postischaemic reperfusion injury in hepatic tissue.

PMID- 18810590
TI  - Bone lengthening with extra-articular arthrodesis of the hip using external
      fixation.
AB  - This is a case series of 11 children and adolescents who underwent femoral
      lengthening and percutaneous hip arthrodesis using a method of extra-articular
      joint compression in combination with callotasis. Clinical review indicated a
      significant improvement in physical function and psychological well-being. The
      average lengthening was 5.3 cm or 16% of the initial length. Complications were
      more frequent in patients older than 14 years (P = 0.034) as was a higher
      maturation index (P = 0.021). No additional operations were required to achieve
      the surgical objective.

PMID- 18810591
TI  - Conservative treatment of ruptured vertebrobasilar dissecting aneurysm: a
      controversial issue in therapeutical management.

PMID- 18810592
TI  - Recruitment criteria for acute disseminated encephalomyelitis studies: the need
      for consensus.

PMID- 18810593
TI  - Molecular medicine: predicting and preventing Huntington's disease.

PMID- 18810594
TI  - Twenty years after Spinnler and Tognoni: new instruments in the Italian
      neuropsychologist's toolbox.
AB  - The aim of this article is to review neuropsychological normative studies which -
      after Spinnler and Tognoni's monograph of 1987 - were done on healthy Italian
      adult subjects, and which either wholly or partially used the Equivalent Scores
      (ES) methodology proposed by Capitani et al. The independent norms settled for
      the same tests have been compared in order to point out their agreement, measured
      by Cohen's Kappa, which in most cases resulted either excellent or good (>0.7).
      Available tests have been classified and arranged to facilitate the most suitable
      choice for different clinical purposes. Moreover, a simple software program has
      been set up which adjusts and transforms raw scores into ES. As well as saving
      time and avoiding errors, this simple aid is likely to improve the quality and
      clarity of the communication of neuropsychological results.

PMID- 18810595
TI  - Recognition of emotions from visual and prosodic cues in Parkinson's disease.
AB  - OBJECTIVE: To assess whether Parkinson Disease (PD) patients are impaired at
      perceiving emotions from facial and prosodic cues and whether any putative
      defective performance concerns recognition of a particular emotion. BACKGROUND:
      Braak et al. [1] demonstrated that in different stages PD pathology involves the
      nigrostriatal system, the amygdala, and the insular cortex. Discrete brain
      lesions to these structures can cause selective deficits in recognising facial
      and prosodic stimuli expressing particular emotions. However, the investigation
      of facial and prosodic emotional processing in PD patients has lead to
      conflicting results. MATERIALS AND METHODS: We compared 27 cognitively unimpaired
      PD patients with control subjects by means of the Facial Emotion Recognition
      Battery and the Emotional Prosody Recognition Battery. RESULTS: PD patients were
      impaired in recognising, selecting, and matching facial affects. In particular,
      the Facial Emotion Recognition Battery demonstrated a severe impairment in
      recognising sad and fearful faces. In the Emotional Prosody Recognition Battery
      PD patients demonstrated a diffuse impairment, including the recognition of
      emotional and propositional prosody. CONCLUSIONS: Face emotion processing is
      impaired in PD patients, with a disproportionate deficit involving fear and
      sadness. The pattern of face expression processing impairment in PD patients
      might depend on the regional distribution of the pathology. The widespread
      involvement of both emotional and propositional prosodic processing parallels the
      aprosodic characteristics of Parkinsonian speech production.

PMID- 18810596
TI  - In vitro study of haematoporphyrin monomethyl ether-mediated sonodynamic effects
      on C6 glioma cells.
AB  - OBJECTIVES: To study the cytotoxicity induced by haematoporphyrin monomethyl
      ether (HMME)-mediated sonodynamic therapy (SDT) on C6 glioma cells. METHODS: The
      potent photosensitizer HMME was used as the sensitizer. Rat C6 glioma cells were
      incubated with HMME (10 microg/mL) in the dark for 2 h and then subjected to
      ultrasound treatment at 1.0 MHz and 0.5 W/cm2 for 2 min. The growth inhibition
      rate at different time points after SDT was determined by MTT assay. The
      apoptotic rate and cell circle profiles were examined with flow cytometry. Fine
      structures were observed with transmission electron microscope (TEM). The
      sonodynamic effect on the glioma cells was also studied in the absence or
      presence of various reactive oxygen species (ROS) scavengers. RESULTS: The growth
      inhibition rate of C6 glioma cells after SDT significantly increased. SDT also
      increased the apoptosis and proliferation rate (APR). TEM examination showed the
      morphological features of apoptosis or necrosis. The addition of NaN(3) showed a
      strong protective effect again SDT. CONCLUSIONS: Our data indicated that SDT
      could kill C6 glioma cells in vitro and possibility through induction of
      apoptosis and necrosis. Singlet oxygen ((1)O2) may play an important role in SDT.

PMID- 18810597
TI  - Sleep disturbance and daytime sleepiness in patients with cirrhosis: a case
      control study.
AB  - Sleep disturbance and excessive daytime sleepiness have been reported in patients
      with hepatic cirrhosis. The objective of this study was to evaluate daytime
      somnolence and sleep complaints in a group of 178 patients with cirrhosis
      compared to a control group. Sleep features and excessive daytime sleepiness were
      evaluated by the Basic Nordic Sleep Questionnaire (BNSQ) and the Epworth
      Sleepiness Scale (ESS). We collected clinical and laboratory data, neurological
      assessment and EEG recordings in cirrhotic patients. Patients with cirrhosis
      complained of more daytime sleepiness (p<0.005), sleeping badly at least three
      times a week (p<0.005), difficulties falling asleep (p<0.01) and frequent
      nocturnal awakening (p<0.005) than controls. We found a poor correlation between
      sleep disorders and clinical or laboratory parameters. Our results confirm
      previous literature reports suggesting a high prevalence of sleep disturbance in
      patients with cirrhosis. Insomnia and daytime sleepiness are the main complaints.
      Sleep disorders are probably a multifactorial phenomenon.

PMID- 18810598
TI  - Conservative treatment of ruptured vertebrobasilar dissecting aneurysm.
AB  - Ruptured vertebrobasilar dissecting aneurysm is usually treated surgically
      because rebleeding negatively affects outcome. However, the risk of rebleeding
      decreases markedly once several hours have passed from the initial bleeding.
      Moreover, surgery-related complications are not rare. We describe seven patients
      with ruptured vertebrobasilar dissecting aneurysm. To prevent rebleeding during
      the acute stage, we treated all seven patients conservatively with fentanyl
      instead of emergency surgery. During the follow-up period (mean 20 months), no
      patient suffered rebleeding. Conservative treatment with fentanyl administration
      may be a good option for management of ruptured vertebrobasilar dissecting
      aneurysm during the acute stage.

PMID- 18810599
TI  - C-reactive protein and aetiological subtypes of cerebral infarction.
AB  - OBJECTIVE: We have sought to relate C-reactive protein (CRP), a peripheral marker
      of inflammation frequently elevated in stroke patients, with aetiology and
      prognosis of acute cerebral infarction. PATIENTS AND METHODS: Patients were
      included after a first-ever CT/MR documented cerebral infarction. CRP was
      measured from blood samples taken within the 6th hour of the onset. Titres of C
      reactive protein were stratified in quartiles. Aetiology of stroke was from TOAST
      criteria. Prognosis was mortality within 14 days of stroke. RESULTS: The study
      included 648 stroke patients. They were 335 women and 313 men, with a mean age of
      70.3 years (median 72). CRP quartiles were mostly increased in cardioembolic
      strokes, After logistic regression analysis CRP remained an independent factor of
      14-day mortality. CONCLUSIONS: Our study suggests that in the acute phase of the
      cerebral infarction CRP might be either a marker of cardioembolism or a
      predictive factor for short-term mortality.

PMID- 18810600
TI  - Relationship between clinical course and Diffusion-weighted MRI findings in
      sporadic Creutzfeldt-Jakob Disease.
AB  - The aim of this study was to investigate the relationship between clinical course
      and diffusion-weighted MRI (DWI) findings in sporadic Creutzfeldt-Jakob Disease
      (sCJD). We reviewed clinical records and MRI examination in nine probable sCJD.
      According to hyperintense signal distribution on DWI, the patients were
      classified into two groups with cortical ribbon plus basal ganglia hyperintensity
      (6/9) and with only increased cortical signals (3/9). Clinical features including
      quadriparesis (3/6), akinetic mutism (2/6), and dysphasia (2/6), which were
      usually observed in the more advanced stage of CJD, were noted only in patients
      with cortical ribbon plus basal ganglia hyperintensity at the time of initial DWI
      examination. The patients with the cortical plus basal ganglia hyperintensity
      (6.4+/-1.7 weeks) had a shorter interval from symptom onset to akinetic mutism
      than those with only cortical ribbon hyperintensity (26.0+/-22.5 weeks) (p=0.02).
      These findings suggest that DWI may predict the clinical course of CJD.

PMID- 18810601
TI  - Handwriting as a gauge of cognitive status: a novel forensic tool for posthumous
      evaluation of testamentary capacity.
AB  - OBJECTIVE: To provide an objective way to analyze handwriting, and to test its
      reliability and correlation with mental deterioration. Handwriting may give clues
      to the cognitive status of the writer, thus its analysis might be helpful, for
      example, in the forensic evaluation of a controversial handwritten last will.
      DESIGN: We devised a semiquantitative score system taking into account verbal and
      lexical skills and spatial orientation. We investigated its inter-rater
      reliability and its correlation with validated tests of neuropsychological
      status, such the Milan Overall Dementia Assessment (MODA) and the Mini Mental
      State Examination (MMSE). SETTING: The neuropsychology service of an academic
      hospital. PATIENTS AND PARTICIPANTS: Consecutive patients referred to the service
      for evaluation of mental deterioration. MEASUREMENTS AND RESULTS: The score
      system we devised has good inter-rater reliability and significantly correlates
      with MODA and with MMSE. CONCLUSIONS: Semiquantitative analysis of handwriting
      may be a useful addition to the methods available for the posthumous evaluation
      of testamentary capacity.

PMID- 18810602
TI  - Late-onset sporadic ataxia, pontine lesion, and retroperitoneal fibrosis: a case
      of Erdheim-Chester disease.
AB  - A 60-year-old man with progressive gait ataxia and mild pyramidal signs showed at
      MRI a pontine lesion with post-contrast enhancement in the left middle cerebellar
      peduncle. Diagnosis of Erdheim-Chester disease (ECD), a rare non-Langerhans cell
      histiocytosis, was suggested, further supported by a previously diagnosed
      retroperitoneal fibrosis. X-ray films demonstrated characteristic bilateral and
      symmetric osteosclerosis of the long bones of the lower limbs, which at
      radionuclide studies exhibited a marked increase in technetium-99 uptake. A
      cerebral 18FDG-PET showed a relevant pontine uptake of the tracer. Re-evaluation
      of a past retroperitoneal biopsy showed an intense CD68+, CD1a-, and S100-
      infiltrate of histiocytes with foamy cytoplasm, thus confirming the diagnosis.
      ECD should be regarded as a rare cause of adult-onset sporadic ataxia, especially
      when pontine lesions and extraneurological manifestations are present.

PMID- 18810603
TI  - Effect of citalopram in treating hypersexuality in an Alzheimer's disease case.
AB  - Hypersexuality in Alzheimer's disease (AD) has been rarely investigated.
      Hypersexual behaviours should be classified as a sexual obsession and included in
      the "obsessive-compulsive disorder-like" spectrum. Hypersexuality has no proven
      treatment, although reports have described reductions of this behaviour using
      antiandrogen treatment, H2-receptor antagonists and antipsychotic drugs.
      Serotonin reuptake blockers seem to be effective in the treatment of sexual
      obsessions or compulsions and less on paraphilic disturbances. We present the
      case of a 54-year-old male patient with Alzheimer's disease with compulsive
      sexual behaviour as reported by his wife. A 18-FDG PET scan evidenced prevalent
      hypometabolism of the right hemisphere, congruent with neuropsychological
      evaluation. Donepezil, 10 mg per day, produced cognitive improvement but no
      effects on sexual behaviour. Therapy with SSRI was subsequently started
      (citalopram): after 60 days, the patient showed improvement in both the
      compulsive pursuit of sex acts and the level of frustration when refused.

PMID- 18810604
TI  - Recovery from acute paraplegia due to spontaneous spinal, epidural hematoma under
      minimal-dose acetyl-salicylic acid.
AB  - OBJECTIVE: Spontaneous spinal epidural hematoma (SEH) has not been reported under
      anti-thrombotic therapy with acetyl-salicylic acid (ASA) in a dosage of 50 mg/d.
      METHODS: Spinal MRI, emergency laminectomy. RESULTS: A 77-yo, HIV-negative female
      under longterm treatment over three years with ASA 50 mg/d for varicositas,
      prescribed by her general practitioner, experienced sudden onset back pain with
      radiation towards both knees after getting up in the morning. One-and-a-half
      hours later she also developed ascending hypesthesia and weakness originating
      from both distal lower limbs. Three hours after onset, hypesthesia had reached
      the T10-level bilaterally and she had become paraplegic. There was reduced
      intestinal motility, stool incontinence, and urinary hesitancy. MRI of the
      thoraco-lumbar spine demonstrated a SEH T9-L1 indenting the dural sack and
      compressing the myelon. Immediately after emergency laminectomy T10-12 with micro
      surgical evacuation of the clot, 12 h after onset, she could move both legs again
      and was able to walk with support 7 days after surgery. CONCLUSIONS: This case
      shows that SEH occurs under a minimal dose of ASA and that such patients rapidly
      recover upon immediate surgical decompression and evacuation of the hematoma.

PMID- 18810605
TI  - Excessive blinking as an initial manifestation of juvenile Huntington's disease.
AB  - Juvenile Huntington's disease (JHD) is mostly characterized by rigidity,
      myoclonus, bradykinesia, dystonia and seizure. We report a 9-year-old male JHD
      patient presenting excessive blinking as the initial symptom two years prior to
      typical JHD symptoms. Genetic analysis revealed expansion of 108 CAG repeats and
      magnetic resonance imaging showed caudate atrophy with lateral ventricular
      enlargement.

PMID- 18810606
TI  - Varicella zoster virus meningo-encephalo-myelitis in an immunocompetent patient.
AB  - OBJECTIVE: To describe clinical, MRI and cerebrospinal fluid (CSF) features of a
      varicella zoster virus (VZV) related meningo-encephalo-myelitis (MEM) without
      rash in an immunocompetent female. PATIENT: An 85 year old immunocompetent woman
      with mild hyperthermia and acute, severe MEM. INTERVENTION: Serum antibodies and
      CSF PCR were searched for several viruses. Brain and spinal cord MRI were
      performed. Immunological profile. TREATMENTS: i.v. acyclovir 30 mg/kg/day; i.v. 6
      MP 125 mg/day. RESULTS: Marked CSF lymphomonocytic pleocytosis, blood
      brainbarrier damage, and PCR detection of 3.05 X 10 6 copies of VZV DNA. MRI
      revealed lesions of the meninges, brain and spinal cord. No evidence of
      immunosuppression. CONCLUSION: We highlight the importance of considering the
      possibility of VZV related MEM, even in immunocompetent patients. We also provide
      a MRI description of VZV related multifocal myelitis, not previously available.
      As supported by other reports, we underline the necessity of a prompt therapeutic
      intervention in this life-threatening condition.

PMID- 18810607
TI  - Melatonin to prevent migraine or tension-type headache in children.
AB  - We designed a 3-month open label trial of melatonin prophylaxis in children with
      primary headache. After a one month baseline period without receiving preventive
      drugs, all children received a 3-month course of melatonin, 3 mg, administered
      orally, at bedtime. A total of 22 children were enrolled (10 boys, mean age
      12.2+/-2.6 years, age range 6-16 years), 13 had recurrent migraine without aura,
      1 with aura and 8 had chronic tension-type headache. When the trial ended, 14 of
      the 21 subjects reported that the headache attacks had decreased by more than 50%
      in respect to baseline and 4 of them reported having no headache attacks. After
      receiving melatonin for one month one subject dropped out because of excessive
      daytime sleepiness. Our promising results warrant randomized placebo-controlled
      trials in children to assess the real effectiveness of melatonin in preventing
      primary headache.

PMID- 18810608
TI  - A case report on pituitary macroadenoma presented as hemichorea hemiballism
      syndrome.

PMID- 18810609
TI  - Assessing the reliability of the Gambling Functional Assessment.
AB  - Dixon and Johnson (Analysis of Gambling Behavior 2007, 1:44-49) introduced the
      Gambling Functional Assessment (GFA), which attempts to identify the consequences
      that may be maintaining a person's gambling behavior. The present study had 949
      introductory psychology students complete the GFA, with 124 of them completing
      the measure a second time 12 weeks later. Measures of internal consistency were
      quite good regardless of whether "non-gamblers" were included or excluded. Test
      retest reliability was somewhat mixed, with Escape scores yielding substandard
      coefficients, especially among females. Both internal and test-retest reliability
      were typically poorer for female respondents. In general, the GFA performed
      within the limits of acceptable reliability, and coefficients compared favorably
      with similar measures. Future investigations will need to determine the
      reliability and validity of the instrument, especially as it pertains to its
      intended population, pathological gamblers.

PMID- 18810610
TI  - Comparison of proportional and differential odds models for mixed-effects
      analysis of categorical data.
AB  - In this work a model for analyzing categorical data is presented; the
      differential odds model. Unlike the commonly used proportional odds model, this
      model does not assume that a covariate affects all categories equally on the log
      odds scale. The differential odds model was compared to the proportional odds
      model, by assessing statistical significance and improvement of predictive
      performance when applying the differential odds model to data previously analyzed
      using the proportional odds model. Three clinical studies; 3-category T-cell
      receptor density data, 5-category diarrhea data and 6-category sedation data,
      were re-analyzed with the differential odds model. As expected, no improvements
      were seen with T-cell receptor density and diarrhea data. However, for the more
      complex measurement sedation, the differential odds model provided both
      statistical improvements and improvements in simulation properties. The estimated
      actual critical value was for all data lower than the nominal value, using the
      number of added parameters as the degree of freedom, i.e. the differential odds
      model is statistically indicated to a less extent than expected. The differential
      odds model had the desired property of not being indicated when not necessary,
      but it may provide improvements when the data does not represent a categorization
      of continuous data.

PMID- 18810611
TI  - Role of endogenous and induced regulatory T cells during infections.
AB  - BACKGROUND: Various populations of regulatory cells, including Foxp3+ T(Reg),
      have been shown to play a central role in the maintenance of peripheral
      homeostasis and establishment of controlled immune responses. OBJECTIVE: In this
      review, we discuss current hypotheses and points of polemic associated with the
      origin, mode of action, and antigen specificity of both endogenous and induced
      regulatory T cells during infections.

PMID- 18810612
TI  - Role of TGF-Beta in the induction of Foxp3 expression and T regulatory cell
      function.
AB  - INTRODUCTION: A number of studies have suggested that transforming growth factor
      beta (TGF-beta) plays a critical role in immune suppression mediated by Foxp3(+)
      regulatory T cells. TGF-beta in concert with interleukin 2 is a potent induction
      factor for the differentiation of Foxp3(+) Treg from naive precursors. Polyclonal
      TGF-beta-induced Treg (iTreg) are capable of preventing the autoimmune syndrome
      that develops in scurfy mice that lack Foxp3(+) Treg. Antigen-specific iTreg can
      be used to both prevent and treat autoimmune gastritis that is induced by
      transfer of naive or primed autoantigen-specific T cells. TGF-beta complexed with
      latency-associated peptide is expressed on the surface of activated thymus
      derived Treg. Coculture of activated Treg with naive responder T cells results in
      the de novo generation of fully functional Foxp3(+) T cells in a contact
      dependent and TGF-beta-dependent manner. CONCLUSIONS AND SPECULATIONS: Generation
      of functional Foxp3(+) T cells via this pathway may represent a mechanism by
      which Treg maintain tolerance and expand their repertoire.

PMID- 18810614
TI  - The use of the MacCAT-CA with adolescents: an item response theory investigation
      of age-related measurement bias.
AB  - Despite the application of the MacCAT-CA to juveniles, questions been raised
      regarding the appropriateness of this tool for adolescents. The current study
      tested for age-related measurement bias using data from the MacArthur Juvenile
      Adjudicative Competence Study (n = 1393). Five of the MacCAT-CA items showed age
      related measurement bias (i.e., DIF) for adolescents aged 11-15, and three items
      showed DIF for adolescents aged 16-17. Several items (e.g., understanding of
      juries) were more difficult for adolescents than adults matched at the same
      latent level of capacity, suggesting that these items might underestimate
      adolescents' legal capacities. Contrary to expectations, there was little
      evidence of age-related measurement bias on the Appreciation scale. The use of
      the MacCAT-CA in research and clinical settings is discussed.

PMID- 18810613
TI  - Interplay between effector Th17 and regulatory T cells.
AB  - INTRODUCTION: Over two decades ago, T helper cells were classified into its
      functional subsets. Soon after the classical observation of Mosmann et al.,
      immunologists agreed to accept the Th1/Th2 paradigm of the T helper subsets. Each
      subset is not only characterized by its specific cytokines pattern and effector
      functions but also by their properties to counter regulate each other's
      functions. This classification helped to understand the complex principles of T
      helper cell biology and allowed us to comprehend different immune reactions in
      context of Th1 and Th2 subsets. DISCUSSION: Although Th1 subsets thought to be
      the crucial player for most of the organ-specific autoimmune diseases like
      multiple sclerosis and type-1 diabetes but the loss of Th1 dominant cytokine, IFN
      gamma did not prevent the development of autoimmunity which raised the
      possibility of involvement of other Th subsets, different from Th1 cells in the
      induction of autoimmunity. CONCLUSION: Recently, a new subset of Th cells that
      predominantly produce IL-17 and induce autoimmunity has been discovered, and it
      is believed that this subset may be the major cell type involved in orchestrating
      tissue inflammation and autoimmunity. Recent data propose that the
      differentiation factors of Th17 cells reveal a link with induction of Foxp3(+)
      regulatory T cells. Here, we review the interplay between Th17 and Foxp3(+) T-reg
      cells and Tr1 cells during autoimmune inflammatory reaction.

PMID- 18810615
TI  - Investigating investigators: how presentation order influences participant
      investigators' interpretations of eyewitness identification and alibi evidence.
AB  - Presentation order of ID and Alibi evidence was manipulated for undergraduate
      participants who conducted a simulated police investigation. Experiment 1 found a
      recency effect when an eyewitness rejected the investigator's suspect. Experiment
      2 also examined order effects, exploring how participant-investigators evaluated
      alibi information in addition to eyewitness ID information. When investigators
      saw the witness identify the suspect but also received a strong alibi for that
      suspect a recency effect occurred, such that whichever piece of information
      occurred at the end of the procedure had the strongest impact on investigators.
      Thus, type of evidence and evidence order both had a dramatic influence on
      participant-investigators' decisions.

PMID- 18810616
TI  - Inconsistent report of pre-pregnancy-recognition alcohol use by Latinas.
AB  - OBJECTIVE: This study compared pregnant Latinas' report of alcohol use for the 3
      month period before pregnancy recognition with two different methods of data
      collection, in an attempt to identify opportunities for improved screening.
      METHODS: Data were collected for 53 pregnant Latinas who have ever drunk alcohol
      and who were receiving services at Women, Infants, and Children (WIC) clinics in
      San Diego, California. This study compared alcohol use reported during in-depth
      research interviews conducted in homes, to responses to an alcohol screening
      question administered by WIC staff. RESULTS: Latinas were more likely to report
      alcohol use for the 3-month period before pregnancy recognition at the in-depth
      home interview than their reported date of last drink to the WIC clinic would
      indicate (70% vs. 15%, respectively). Of importance, 57% of home interview
      reports that were positive for pre-pregnancy-recognition alcohol use would not
      have been identified by their reported date of last drink to the WIC screening
      question. Younger age, higher income, and earlier recognition of pregnancy were
      associated with under-reporting of pre-pregnancy-recognition alcohol use.
      CONCLUSIONS: Reporting of pre-pregnancy-recognition alcohol use may be influenced
      by the circumstances and scope of the screening questions employed, and varies by
      respondent's characteristics. Asking about pre-pregnancy-recognition alcohol use,
      i.e., alcohol consumed before pregnancy is recognized, may improve identification
      of low-income pregnant Latinas who may benefit from targeted intervention
      services.

PMID- 18810617
TI  - Assessing awareness, knowledge and use of folic acid in Kansas women between the
      ages of 18 and 44 years.
AB  - Taking folic acid daily, before and during early pregnancy, has been proven to
      reduce neural tube birth defects (NTD). Unfortunately, many women fail to take it
      daily as recommended. OBJECTIVES: To assess women's self-reported awareness,
      knowledge and use of folic acid. Methods Data were obtained by cross-sectional,
      random digit-dialing, computer-assisted telephone interviews with 250 women in
      Kansas. Associations were determined by chi-squared analysis. RESULTS: Eighty
      eight percent of childbearing age women in Kansas have a general awareness of
      folic acid, 20% have knowledge that it reduces birth defects, but only 25% report
      taking it daily. Awareness was associated with high school or greater education
      (P < .0001), incomes over $25,000 (P = 0.0003), being married (P = 0.0035), being
      white (P = 0.0135), having health insurance (P = 0.0152) and being capable of
      pregnancy (P = 0.0119). Knowledge that folic acid reduces birth defects was
      associated with being aware of the USPHS recommendation (P < .0001), being
      capable of pregnancy (P = 0.0043), being pregnant (P = 0.0061), and being aware
      of folic acid (P = 0.0379). Taking folic acid daily was associated with currently
      being pregnant (P = 0.0126). CONCLUSIONS: Women less likely to take folic acid on
      a daily basis were young, non-Caucasians who reported less education, less income
      and no health insurance. Based upon these data, multi-level education campaigns
      that specifically target lower-SES women should be considered.

PMID- 18810618
TI  - Source of antenatal care influences facility delivery in rural Tanzania: a
      population-based study.
AB  - OBJECTIVE: While antenatal care does not directly contribute to reducing maternal
      mortality, it may play an indirect role by encouraging women to deliver with a
      skilled birth attendant or in a health facility. We investigated whether the
      frequency of visits and select characteristics of antenatal care were associated
      with facility delivery. METHODS: We selected a population-representative sample
      of households in a rural district of western Tanzania. Women who had given birth
      within five years were asked about their most recent delivery and antenatal care.
      RESULTS: Of 1,204 women interviewed, 1,195 (99.3%) made at least one antenatal
      care visit, while only 438 (36.4%) delivered in a health facility. In adjusted
      analysis, women were significantly more likely to deliver in a health facility if
      they attended antenatal care at a government health center (OR 3.17, 95% CI: 1.60
      6.30) or a mission facility (OR 2.87, 95% CI: 1.36-6.07), rather than a
      government dispensary. Women were significantly less likely to deliver in a
      health facility if their nearest health facility was outside their village (OR
      0.38, 95% CI: 0.22-0.66). CONCLUSION: Though facility utilization for antenatal
      care is frequent, most women who accessed antenatal care did not deliver in a
      health facility. Women who obtained antenatal care at higher level government
      facilities or mission facilities, which offered better quality of care, were more
      likely to deliver in any facility. Improving the quality of antenatal care may
      improve the health of mothers through encouraging women to return to facilities
      for delivery.

PMID- 18810619
TI  - Want your paper published faster? Read on...
AB  - After nearly 5 years and 24 issues, the editor offers some tips to authors
      seeking the fastest route to seeing their work in print.

PMID- 18810620
TI  - Clinical criteria for predicting benefit of ICD/PM in post myocardial infarction
      patients: an AVID and CAST analysis.
AB  - BACKGROUND: Three clinical factors from the Antiarrhythmics Versus Implantable
      Defibrillators (AVID) trial-heart failure, left ventricular dysfunction and
      certain historical features defined a subgroup in which an implantable
      cardioverter defibrillator (ICD/PM) has a mortality advantage over amiodarone.
      METHODS: These three factors were jointly evaluated in the AVID cohort with
      ischemic heart disease (IHD) and the results applied in placebo-treated post
      infarction patients in the cardiac arrhythmia suppression trial (CAST). RESULTS:
      Similar predictive power was noted in AVID patients with IHD. In CAST the factors
      defined three groups; one group (5.8%), corresponding to AVID patients that had
      high risk and benefited from an ICD/PM and another group (17.2%) corresponding to
      patients in AVID where the risk was moderate and ICD/PM and amiodarone had equal
      efficacy, demonstrated a two-fold higher risk of sudden arrhythmic than non
      arrhythmic death and hence would be expected to benefit from antiarrhythmia
      therapy. The third group, corresponding to AVID patients with low risk of
      arrhythmia, demonstrated similar and low risks of sudden arrhythmic and non
      arrhythmic death. Thus this group (77%) is unlikely to benefit from
      indiscriminate antiarrhythmia therapy. Onset of risk of death in CAST patients
      was offset from randomization by 3 to 6 months. CONCLUSIONS: Readily available
      clinical criteria identify a small group likely to benefit from an ICD/PM after
      recent myocardial infarction (MI) and the remainder unlikely to benefit from
      nonselective ICD/PM therapy. Additional risk stratification should focus on the
      latter patients and be timed to allow ICD/PM implantation between 2 and 6 months
      after MI.

PMID- 18810622
TI  - The effect of different treatment strategies on left atrial size in patients with
      lone paroxysmal atrial fibrillation-a prospective cohort study.
AB  - INTRODUCTION: The effect of different treatment strategies of atrial fibrillation
      on left atrial (LA) size has not been compared in lone paroxysmal atrial
      fibrillation. The objective of the present study was to evaluate the evolution of
      LA size over time in patients who underwent different treatment interventions.
      METHODS AND RESULTS: Two hundred forty patients with lone paroxysmal atrial
      fibrillation were assigned to four groups. The circumferential pulmonary vein
      ablation (CPVA) group (n = 60) was treated with CPVA, segmental pulmonary vein
      isolation (SPVI) group (n = 60) with SPVI, AMIO group (n = 60) with amiodarone
      alone, and AMIO + LO group (n = 60) with amiodarone plus losartan. LA diameter
      was measured with transthoracic echocardiogram at baseline, 3, 6, 9, and 12
      months after the interventions. In the CPVA group, LA size at third, sixth,
      ninth, and 12th month had a significant decrease than that at baseline and in the
      other three groups. LA size in patients with atrial fibrillation recurrence in
      the four groups was significant higher than that in patients with no atrial
      fibrillation recurrence (P = 0.002-0.001). CONCLUSION: The results suggested that
      a shortened LA size is not consistent with improved sinus rhythm maintenance.
      Although maintenance of sinus rhythm is not the only factor in determining
      shrinking or enlargement of the left atrium, inhibiting or eliminating activity
      of the pulmonary vein is very important for paroxysmal atrial fibrillation.
      Atrial fibrillation recurrence is a main factor contributing to enlargement of
      the LA.

PMID- 18810621
TI  - Implantable CRT device diagnostics identify patients with increased risk for
      heart failure hospitalization.
AB  - PURPOSE: To determine the association between device-determined diagnostic
      indices, including intrathoracic impedance, and heart failure (HF)
      hospitalization. METHODS: Clinical and device diagnostic data of 558 HF patients
      indicated for CRT-D therapy (In Sync Sentry, Medtronic Inc.) were prospectively
      collected from 34 centers. Device-recorded intrathoracic impedance fluid index
      threshold crossing event (TCE), mean activity counts, tachyarrhythmia events,
      night heart rate (NHR) and heart rate variability (HRV) were compared within
      patients with vs. without documented HF hospitalization. RESULTS: Mean follow-up
      was 326 +/- 216 days. Patients hospitalized for HF had significantly higher rates
      of TCE, a higher percentage of days with the thoracic impedance fluid index above
      the programmed threshold, a higher percentage of days with low activity, with low
      HRV or with high NHR. Multivariate analysis showed that TCE resulted in a 36%
      increased probability of HF hospitalization. Both TCE duration and patient
      activity were also significantly associated with hospitalization. Kaplan Meier
      analysis indicated that patients with more TCE events were significantly more
      likely to be hospitalized (log rank test, p = 0.005). CONCLUSIONS: Decreased
      intrathoracic impedance, low patient activity and low HRV were all independently
      associated with increased risk for HF hospitalization in HF patients treated with
      resynchronization therapy. Device-derived diagnostic data may provide valuable
      and reliable indices for the prognostic stratification of HF patients.

PMID- 18810623
TI  - An unusual case of permanent junctional reciprocating tachycardia: Successful
      ablation at the mitral annulus-aorta junction.
AB  - A 25-year-old woman with drug-refractory permanent junctional reciprocating
      tachycardia (PJRT) and a previous failed ablation, was referred to our
      institution. Electrophysiological study confirmed the diagnosis of orthodromic
      atrioventricular reentry tachycardia using a slowly conducting accessory pathway.
      This accessory pathway was successfully ablated by conventional radiofrequency at
      the left anteroseptal region using a transseptal approach. Catheter ablation of
      this accessory pathway (Coumel type) at the mitral annulus-aorta junction offers
      insights on a rare anatomical location of PJRT.

PMID- 18810624
TI  - Comparison of atrial fibrillation inducibility by electrical stimulation of
      either the extrinsic or the intrinsic autonomic nervous systems.
AB  - OBJECTIVES: To study the effects of bilateral vagosympathetic nerve stimulation
      (VNS) and ganglionated plexi stimulation (GPS) on atrial refractoriness and
      inducibility of atrial fibrillation (AF). METHODS: Studies were performed in
      fourteen adult mongrel dogs anesthetized with Na-pentobarbital, 30 mg/kg. VNS was
      achieved by insertion of wires into the left and right VN trunks. An octapolar
      catheter was attached to contact the right superior pulmonary vein (RSPV) and
      other octapolar catheter electrodes were sutured to the right atrial (RA) free
      wall and appendage (RAA). GPS was performed via a plaque electrode sutured to the
      fat pad containing the anterior right (AR) GP. VNS and GPS were matched to
      decrease heart rate by approximately 50%. Programmed stimulation delivered from
      the RSPV or RAA at 2x, 4x and 10x threshold (TH) allowed the determination of
      atrial refractory period (ARP) and the AF inducibility. The latter was
      quantitated by the cumulative window of vulnerability (WOV), i.e., the longest
      minus the shortest coupling interval during which AF was induced at 2x, 4x, 10x,
      TH combined. RESULTS: Programmed electrical stimulation at the RSPV showed that
      the ARP was significantly shorter for both VNS and GPS than baseline (baseline,
      113 +/- 22 ms; VNS, 94 +/- 26 ms; GPS, 85 +/- 31 ms) but there was no significant
      difference in ARP between VNS and GPS. In contrast, the cumulative WOV was
      significantly wider with GPS (39 +/- 36 ms) than either the baseline state (1 +/-
      1 ms) or with VNS (14 +/- 26 ms), p < 0.05. Moreover, pacing from RAA showed a
      significantly greater cumulative WOV for VNS (33 +/- 36 ms) vs both baseline and
      GPS (1 +/- 4 ms and 15 +/- 26 ms, respectively, p < 0.05). The heart rate slowing
      caused by GPS and VNS was not significantly different, 82 +/- 11/min vs 82 +/-
      7/min. CONCLUSIONS: These data indicate a distinct functional separation of
      autonomic nerve innervation to the atria from the extrinsic and intrinsic nervous
      systems. AF is more liable to occur due to intrinsic nerve stimulation at the PVs
      whereas peripheral atrial sites are more readily inducible for AF due to the
      extrinsic neural input.

PMID- 18810625
TI  - Acute superior vena cava syndrome after insertion of implantable cardioverter
      defibrillator.
AB  - We describe a rare case of superior vena cava syndrome that occurred a few hours
      after insertion of an implantable cardioverter defibrillator through the right
      subclavian vein in a patient with previous dual chamber DDD pacemaker. The
      patient was successfully treated with anticoagulant therapy showing a fast
      clinical and instrumental improvement.

PMID- 18810626
TI  - Brief report: decoding representations: how children with autism understand
      drawings.
AB  - Young typically developing children can reason about abstract depictions if they
      know the intention of the artist. Children with autism spectrum disorder (ASD),
      who are notably impaired in social, 'intention monitoring' domains, may have
      great difficulty in decoding vague representations. In Experiment 1, children
      with ASD are unable to use another person's eye gaze as a cue for figuring out
      what an abstract picture represents. In contrast, when the participants
      themselves are the artists (Experiment 2), children with ASD are equally
      proficient as controls at identifying their own perceptually identical pictures
      (e.g. lollipop and balloon) after a delay, based upon what they intended them to
      be. Results are discussed in terms of intention and understanding of visual
      representation in autism.

PMID- 18810627
TI  - Use of vocational rehabilitative services among adults with autism.
AB  - This study examined the experiences of individuals with autism spectrum disorders
      (ASD) in the US Vocational Rehabilitation System (VRS). Subjects included all
      382,221 adults ages 18-65 served by this system whose cases were closed in 2005;
      1,707 were diagnosed with ASD. Adults with ASD were more likely than adults with
      other impairments to be denied services because they were considered too severely
      disabled. Among those served, adults with ASD received the most expensive set of
      services. They and adults with MR were most likely to be competitively employed
      at case closure. Post hoc analyses suggest that their employment was highly
      associated with on-the-job supports. The results suggest the importance of the
      VRS in serving adults with ASD.

PMID- 18810628
TI  - Comparative sequence analyses of a new mammalian reovirus genome and the
      mammalian reovirus S1 genes from six new serotype 2 human isolates.
AB  - We previously described isolation of a potentially new mammalian reovirus,
      designated BYD1, which can cause clinical symptoms similar to that of severe
      acute respiratory syndrome (SARS) in guinea pigs and macaques, from throat swabs
      of one SARS patient of Beijing, in 2003. For this study, we determined the genome
      sequences of BYD1 and the S1 gene sequences of other five mammalian reovirus
      isolates (BLD, JP, and BYL were isolated from different SARS patients during the
      outbreak, 302I and 302II were isolated from fecal specimens of two children of
      Beijing in 1982) to allow molecular comparison with other previously reported
      mammalian reoviruses (MRVs). Comparative analyses of the BYD1 genome with those
      of three prototype mammalian reovirus strains demonstrated that BYD1 is a novel
      reassortant virus, with its S1 gene segment coming from a previously unidentified
      serotype 2 isolate and other nine segments coming from ancestors of homologous
      T1L and T3D segments, which supports the hypothesis that mammalian reovirus gene
      segments reassort in nature. Further analyses of the S1 segments of the six
      isolates showed that all the isolates are novel serotype 2 MRVs based on their S1
      gene sequences, which are markedly different from those of all previously
      reported, and the S1 genes of the four new isolates share more than 99% identity
      with each other, proving that they diverged from a common ancestor most recently,
      and the S1 genes of the four new isolates share about 65% identity with those of
      the two strains isolated in 1982.

PMID- 18810629
TI  - Dissecting "gaydar": accuracy and the role of masculinity-femininity.
AB  - "Gaydar" is the ability to distinguish homosexual and heterosexual people using
      indirect cues. We investigated the accuracy of gaydar and the nature of "gaydar
      signals" conveying information about sexual orientation. Homosexual people tend
      to be more sex atypical than heterosexual people in some behaviors, feelings, and
      interests. We hypothesized that indicators of sex atypicality might function as
      gaydar signals. In Study 1, raters judged targets' sexual orientation from
      pictures, brief videos, and sound recordings. Sexual orientation was assessed
      with high, though imperfect, accuracy. In Study 2, different raters judged
      targets' sex atypicality from the same stimuli. Ratings of sexual orientation
      from Study 1 corresponded highly with targets' self-reports of sex atypicality
      and with observer ratings of sex atypicality from Study 2. Thus, brief samples of
      sex-atypical behavior may function as effective gaydar signals.

PMID- 18810630
TI  - Avuncular tendencies and the evolution of male androphilia in Samoan fa'afafine.
AB  - The kin selection hypothesis for male androphilia holds that genes for male
      androphilia can be maintained in a population if the fitness costs of not
      reproducing directly are offset by enhancing indirect fitness. Kin share some
      proportion of genes identical by virtue of descent. Theoretically speaking,
      androphilic males can increase their fitness indirectly by allocating altruistic
      behavior toward kin, which, in turn, allows kin to increase their reproductive
      success. Research conducted in Independent Samoa has shown that androphilic males
      (known locally as fa'afafine) report significantly higher avuncular tendencies
      relative to gynephilic men. Here, we replicate this sexual orientation
      difference, using a larger, independent sample, suggesting that the documented
      sexual orientation difference in avuncular tendencies in Independent Samoa is
      genuine. We also extend previous research by showing that fa'afafine exhibit
      significantly higher avuncular tendencies even when compared to a more closely
      matched control group that also lacks direct parental care responsibilities
      (i.e., gynephilic men with no children). Although the greater avuncular
      tendencies of fa'afafine relative to gynephilic men are consistent with the
      predictions of the kin selection hypothesis for male androphilia, further
      research is needed before deeming male androphilia an adaptation for promoting
      elevated avuncularity. Likewise, more research is needed before deeming elevated
      avuncularity in fa'afafine an evolved adaptation for promoting indirect fitness.
      We discuss these findings in the context of alternative evolutionary explanations
      for male androphilia (i.e., an evolved by-product of an adaptation).

PMID- 18810631
TI  - Efficient calculation of empirical P-values for genome-wide linkage analysis
      through weighted permutation.
AB  - Linkage analysis in multivariate or longitudinal context presents both
      statistical and computational challenges. The permutation test can be used to
      avoid some of the statistical challenges, but it substantially adds to the
      computational burden. Utilizing the distributional dependencies between p
      (defined as the proportion of alleles at a locus that are identical by descent
      (IBD) for a pairs of relatives, at a given locus) and the permutation test we
      report a new method of efficient permutation. In summary, the distribution of p
      for a sample of relatives at locus x is estimated as a weighted mixture of p
      drawn from a pool of 'representative' p distributions observed at other loci.
      This weighting scheme is then used to sample from the distribution of the
      permutation tests at the representative loci to obtain an empirical P-value at
      locus x (which is asymptotically distributed as the permutation test at loci x).
      This weighted mixture approach greatly reduces the number of permutation tests
      required for genome-wide scanning, making it suitable for use in multivariate and
      other computationally intensive linkage analyses. In addition, because the
      distribution of p is a property of the genotypic data for a given sample and is
      independent of the phenotypic data, the weighting scheme can be applied to any
      phenotype (or combination of phenotypes) collected from that sample. We
      demonstrate the validity of this approach through simulation.

PMID- 18810632
TI  - Low grade inflammation, as evidenced by basal high sensitivity CRP, is not
      correlated to outcome measures in IVF.
AB  - PURPOSE: To assess the relationship between low-grade inflammation, measured as
      basal high sensitivity (hs)-CRP, and IVF outcome. METHODS: We recruited a total
      of 220 women undergoing infertility work up prior to IVF. Patients were selected
      for a BMI < 30 kg/m(2) with an upper age limit of 40 years. Serum hs-CRP levels
      were measured on day 3 of a spontaneous menstrual cycle preceding ovarian
      stimulation. A sensitive two-site ELISA was used for analysis. Dose of
      gonadotrophins required, follicles days 8 and 10, number of oocytes collected,
      number of oocytes fertilised and pregnancy outcome were recorded. RESULTS: Median
      hs-CRP was 1.08 mg/L (0.43-3.00 mg/L). The hs-CRP was significantly related to
      BMI (r = 0.386, P < .001) but not to age and smoking habit. There were no
      significant relationships between basal hs-CRP and any of the measured IVF
      outcomes. CONCLUSIONS: These findings demonstrate that serum hs-CRP concentration
      is not a predictive marker of cycle or pregnancy outcome in women undergoing IVF
      treatment.

PMID- 18810633
TI  - Clinical outcome of magnetic activated cell sorting of non-apoptotic spermatozoa
      before density gradient centrifugation for assisted reproduction.
AB  - PURPOSE: Magnetic activated cell sorting (MACS) eliminates apoptotic spermatozoa
      based on the presence of externalized phosphatidylserine residues. We evaluated
      the outcome of male fertility treatment when intracytoplasmic sperm injection
      (ICSI) into human oocytes was performed with non-apoptotic MACS-selected
      spermatozoa. METHODS: 196 couples were treated by ICSI following spermatozoa
      preparation by MACS (study group; 122 couples) or density gradient centrifugation
      (DGC) (control group; 74 couples). Fertilization, cleavage, pregnancy, and
      implantation rates were analyzed. RESULTS: The percentage of sperm with normal
      morphology after MACS selection was improved. Cleavage and pregnancy rates were
      higher, respectively, in the study group than in control. A slightly higher
      implantation rate was also observed in the study group. CONCLUSIONS: MACS
      selection of human spermatozoa increased cleavage and pregnancy rates in
      oligoasthenozoospermic ART cases. This novel method for selecting non-apoptotic
      spermatozoa for ICSI is safe and reliable, and may improve the assisted
      reproduction outcome.

PMID- 18810634
TI  - Implication of the cystic fibrosis transmembrane conductance regulator gene in
      infertile family members of Indian CF patients.
AB  - Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the
      CFTR gene. Among males with CF, 95% are infertile due to congenital absence of
      the vas deferens. We investigated the role of family history of infertility among
      CF subjects and characterized mutations in them. Among 50 CF subjects, four had a
      family history of infertility. A homozygous c.1521_1523delCTT mutation was
      detected in one, two had a compound heterozygous genotype
      (c.1521_1523delCTT/c.3717 + 10 kbC>T), and c.1521_1523delCTT mutation was
      identified on one allele of fourth CF subject. Genetic analysis of each infertile
      family members of CF subjects revealed the c.1521_1523delCTT mutation on one
      allele; however, no mutation could be identified on other allele. Haplotype
      analysis of the infertile family members showed that at least one of the alleles
      shared the same haplotype as that of the index case. It is suggested that the
      CFTR gene is implicated in the infertile members of the CF families. Failure to
      detect mutations on the other allele by SSCP analysis demands direct gene
      sequencing to detect mutations in the intronic or promoter region.

PMID- 18810635
TI  - Functional characterization of an eosinophil-specific galectin, ovine galectin
      14.
AB  - Across mammalian species, human galectin-10 and ovine galectin-14 are unique in
      their expression in eosinophils and their release into lung and gastrointestinal
      tissues following allergen or parasite challenge. Recombinant galectin-14 is
      active in carbohydrate binding assays and has been used in this study to unravel
      the function of this major eosinophil constituent. In vitro cultures revealed
      that galectin-14 is spontaneously released by eosinophils isolated from allergen
      stimulated mammary gland lavage, but not by resting peripheral blood eosinophils.
      Galectin-14 secretion from peripheral blood eosinophils can be induced by the
      same stimuli that induce eosinophil degranulation. Flow cytometric analysis
      showed that recombinant galectin-14 can bind in vitro to eosinophils, neutrophils
      and activated lymphocytes. Glycan array screening indicated that galectin-14
      recognizes terminal N-acetyllactosamine residues which can be modified with
      alpha1-2-fucosylation and, uniquely for a galectin, prefers alpha2- over alpha2
      sialylation. Galectin-14 showed the greatest affinity for lacto-N-neotetraose, an
      immunomodulatory oligosaccharide expressed by helminths. Galectin-14 binds
      specifically to laminin in vitro, and to mucus and mucus producing cells on lung
      and intestinal tissue sections. In vivo, galectin-14 is abundantly present in
      mucus scrapings collected from either lungs or gastrointestinal tract following
      allergen or parasite challenge, respectively. These results suggest that in vivo
      secretion of eosinophil galectins may be specifically induced at epithelial
      surfaces after recruitment of eosinophils by allergic stimuli, and that
      eosinophil galectins may be involved in promoting adhesion and changing mucus
      properties during parasite infection and allergies.

PMID- 18810636
TI  - Endoscopic injection sclerotherapy with ethanolamine oleate with iopamidol for
      esophagojejunal varices in idiopathic portal hypertension.

PMID- 18810637
TI  - Incomplete fixation of the colon ascendens and an unusually located peritoneal
      fold together with direct inguinal hernia.
AB  - During abdominal dissection of a male cadaver, aged 60 years at death, a
      peritoneal fold formed by mesentery of the terminal ileum and attached to the
      anterior wall was encountered in the abdominal cavity. Distal part of the
      terminal ileum, cecum, and colon ascendens were herniated from the medial
      inguinal fossa. The unusually located peritoneal fold was interpreted as a
      predisposing factor for the accompanying direct inguinal hernia. The subject is
      discussed in terms of embryonic development of the midgut.

PMID- 18810638
TI  - Language barriers among patients in Boston emergency departments: use of medical
      interpreters after passage of interpreter legislation.
AB  - BACKGROUND: Since 2001, Massachusetts state law dictates that emergency
      department (ED) patients with limited English proficiency have the right to a
      professional interpreter. METHODS: One year later, for two 24-h periods, we
      interviewed adult patients presenting to four Boston EDs. We assessed language
      barriers and compared this need with the observed use and type of interpreter
      during the ED visit. RESULTS: We interviewed 530 patients (70% of eligible) and
      estimated that an interpreter was needed for 60 (11%; 95% confidence interval, 7
      12%) patients. The primary interpreter for these clinical encounters was a
      physician (30%), friend or family member age >or=18 years (22%), hospital
      interpreter services (15%), younger family member (11%), or other hospital staff
      (17%). CONCLUSIONS: We found that 11% of ED patients had significant language
      barriers, but use of professional medical interpreters remained low. One year
      after passage of legislation mandating access, use of professional medical
      interpreters remained inadequate.

PMID- 18810639
TI  - Modeling fluorescence recovery after photobleaching in loaded bone: potential
      applications in measuring fluid and solute transport in the osteocytic lacunar
      canalicular system.
AB  - Solute transport through the bone lacunar-canalicular system is essential for
      osteocyte viability and function, and it can be measured using fluorescence
      recovery after photobleaching (FRAP). The mathematical model developed here aims
      to analyze solute transport during FRAP in mechanically loaded bone. Combining
      both whole bone-level poroelasticity and cellular-level solute transport, we
      found that load-induced solute transport during FRAP is characterized by an
      exponential recovery rate, which is determined by the dimensionless Strouhal (St)
      number that characterizes the oscillation effects over the mean flows, and that
      significant transport occurs only for St values below a threshold, when the
      solute stroke displacement exceeds the distance between the source and sink (the
      canalicular length). This threshold mechanism explains the general flow behaviors
      such as increasing transport with increasing magnitude and decreasing frequency.
      Mechanical loading is predicted to enhance transport of all tracers relative to
      diffusion, with the greatest enhancement for medium-sized tracers and less
      enhancement for small and large tracers. This study provides guidelines for
      future FRAP experiments, based on which the model can be used to quantify bone
      permeability, solute-matrix interaction, and flow velocities. These studies
      should provide insights into bone adaptation and metabolism, and help to treat
      various bone diseases and conditions.

PMID- 18810640
TI  - Antioxidant activity and chemical characterization of essential oil of Bunium
      persicum.
AB  - The search for natural antioxidants, especially of plant origin, has notably
      increased in recent years. Bunium persicum Boiss. is an economically important
      medicinal plant growing wild in the dry temperature regions in Iran. In this
      study, chemical constituents of the essential oil of the seed from Bunium
      persicum Boiss. have been studied by GC/MS technique. The major components were
      caryophyllene (27.81%), gamma-terpinene (15.19%), cuminyl acetate (14.67%).
      Individual antioxidant assays such as, DPPH* scavenging activity and beta
      carotene bleaching have been carried out. In DPPH* system, the EC(50) value of
      essential oil was determined as 0.88 mg/mL. In beta-carotene bleaching
      antioxidant activity of essential oil (0.45%) was almost equal to BHT at 0.01%.
      In addition, the antioxidant activity of the essential oil was evaluated in crude
      soybean oil by monitoring peroxide and thiobarbituric acid values of the oil
      substrate. The results showed that the Bunium persicum essential oil (BPEO) was
      able to reduce the oxidation rate of the soybean oil in the accelerated condition
      at 60 degrees C (oven test). The essential oil at 0.06% showed the same effect of
      BHA at 0.02%. Hence, BPEO could be used as an additive in food after screening.

PMID- 18810641
TI  - Carotenoid content of underutilized tropical fruits.
AB  - This study was conducted to evaluate the total carotene content (TCC) and beta
      carotene (BC) in the selected underutilized tropical fruits. TCC of underutilized
      fruits estimated by spectrophotometric method was in the range of 1.4-19.8 mg/100
      g edible portion. The TCC of these fruits decreased in the order: Jentik-jentik >
      Durian Nyekak 2 > Durian Nyekak 1 > Cerapu 2 > Cerapu 1 > Tampoi Kuning > Bacang
      1 > Kuini > Jambu Mawar > Bacang 2 > Durian Daun > Bacang 3 > Tampoi Putih >
      Jambu Susu. BC contents estimated by HPLC method were highest in Jentik-jentik,
      followed by Cerapu 2, Durian Nyekak 2, Tampoi Kuning, Durian Nyekak 1, and Cerapu
      1, which had a range of 68-92% of BC in TCC. These underutilized fruits have an
      acceptable amount of carotenoids that are potential antioxidant fruits.

PMID- 18810642
TI  - Preparation of monodispersed chitosan microspheres and in situ encapsulation of
      BSA in a co-axial microfluidic device.
AB  - This work describes a novel microfluidic method to prepare monodispersed chitosan
      microspheres by using the solvent extraction method. Our strategy is that a
      chitosan/acetic acid aqueous solution is emulsified in an organic phase
      containing the extractant by using the co-flowing shear method in a co-axial
      microfluidic device. The formed droplets are in situ solidified within a
      synthesizing channel by the extraction of acetic acid from the chitosan aqueous
      droplets to the organic solution. Based on this approach, the size of chitosan
      microspheres can be successfully controlled from 100 mum to 700 mum in diameter
      with a variation of less than 4%. Furthermore, high loading efficiency (>95%) of
      Bovine serum albumin (BSA) can be in situ encapsulated. The present method has
      the advantages of actively controlling the droplet diameter, narrow size
      distribution, good sphericity, and having a simple and low cost process, with a
      high throughput. This approach for the preparation of chitosan microspheres will
      provide many potential applications for pharmaceutical area.

PMID- 18810643
TI  - Autonomous capillary system for one-step immunoassays.
AB  - Autonomous capillary systems (CSs), in which liquids are transported owing to
      capillary forces, have been previously used to perform fast and sensitive multi
      step immunoassays using minute volumes of analyte. CSs for diagnostic
      applications have different requirements than CSs that are used as a research
      tool in life sciences, where a high flexibility and performance prevail over ease
      of use and portability. In this paper a proof-of-concept for one-step
      immunoassays based on CSs is demonstrated. This proof-of-concept is based on
      preloading detection antibodies (dAbs) on the flow path of analytes and
      redissolving these antibodies to form dAb-analyte complexes, which can be
      detected using fluorescence downstream on accurately patterned capture
      antibodies. A user therefore only needs to load a sample at the beginning of a CS
      and obtains the result of the assay using a conventional fluorescence microscope
      or scanner. As an example, C-reactive protein was detected in human serum at
      clinical concentrations within 10 min and using only microL of sample.

PMID- 18810644
TI  - Breast self-examination in long-term breast cancer survivors.
AB  - INTRODUCTION: For many breast cancer survivors, continued surveillance will be
      necessary to increase the possibility of finding a new diagnosis in an early
      stage. One such surveillance approach, breast self-examination, has not been
      studied specifically in breast cancer survivors. The current study was designed
      to assess the practice of BSE in a sample of long-term breast cancer survivors,
      and to examine the personal, emotional, cognitive, and health-care provider
      factors that may contribute to its performance. METHODS: Three hundred forty-five
      breast cancer survivors (34% response rate, 345/1,001) diagnosed with in situ
      stage II breast cancer between 1997-2004 at a community hospital provided answers
      to a mailed, self-report questionnaire. RESULTS: Seventy-six percent of
      respondents reported that they had performed a BSE in the last 30-days. Forty
      percent reported performing BSE once/month, 39% more than once/month, and 21%
      less than once/month since their diagnosis. Most of the women (90%) reported that
      a doctor or nurse told them to perform a BSE once/month since their diagnosis,
      although only 69% had actually been shown how to perform a BSE. Consistently, the
      perception of increased barriers to BSE performance was associated with
      performance of BSE less than once/month (OR = 1.4, 95% CI 1.2, 1.6; OR = 0.8, 95%
      CI 0.8, 0.9). In addition, depending on the model, age (OR = 1.1, 95% CI 1.0,
      1.2), perceived effectiveness of cancer treatments (OR = 0.7, 95% CI 0.5, 0.9),
      and perceived benefits of BSE (OR = 0.8, 95% CI 0.7, 0.9) also was associated
      with differences in BSE performance. CONCLUSION: The current study suggests that
      breast cancer survivors between 4 and 11 years from diagnosis practice BSE,
      although their perception of the barriers to conducting BSE influences the
      frequency of this behavior. Further examination is needed to understand why some
      survivors perceive greater barriers to BSE performance than others. Also needed
      is a prospective examination of BSE performance using behavioral measures in
      relation to self-report. IMPLICATIONS FOR CANCER SURVIVORS: Increased attention
      should be paid to this particular screening behavior performed by a majority of
      breast cancer survivors by both researchers and health-care providers alike.
      Whether survivors perform the behavior correctly and the impact it has on their
      emotional and cognitive well-being should be further explored.

PMID- 18810645
TI  - Chemical shift based editing of CH3 groups in fractionally 13C-labelled proteins
      using GFT (3, 2)D CT-HCCH-COSY: stereospecific assignments of CH3 groups of Val
      and Leu residues.
AB  - We propose a (3, 2)D CT-HCCH-COSY experiment to rapidly collect the data and
      provide significant dispersion in the spectral region containing (13)C-(1)H cross
      peaks of CH(3) groups belonging to Ala, Ile, Leu, Met, Thr and Val residues. This
      enables one to carry out chemical shift based editing and grouping of all the
      (13)C-(1)H cross peaks of CH(3) groups belonging to Ala, Ile, Leu, Met, Thr and
      Val residues in fractionally (10%) (13)C-labelled proteins, which in turn aids in
      the sequence-specific resonance assignments in general and side-chain resonance
      assignments in particular, in any given protein. Further, we demonstrate the
      utility of this experiment for stereospecific assignments of the pro-R and pro-S
      methyl groups belonging to the Leu and Val residues in fractionally (10%) (13)C
      labelled proteins. The proposed experiment opens up a wide range of applications
      in resonance assignment strategies and structure determination of proteins.

PMID- 18810646
TI  - Simultaneous excision of two transgene flanking sequences and resolution of
      complex integration loci.
AB  - In planta excision techniques have proven useful both for basic biology and
      applied biotechnology. In this report, we describe a simple site-specific
      recombination (SSR) strategy that simultaneously removes pre-defined DNA
      sequences from both sides of a transgenic "gene of interest," leaving only the
      desired gene and short sequences from the recombinase recognition site. We have
      used the FLP/FRT SSR system to provide a proof of concept, though any of several
      other SSR systems could be used in the same way. The frequency of double excision
      ranged from 33% to 83% in different transgenic lines. We show that a single SSR
      reaction can simultaneously carry out double excisions and resolve complex
      transgene loci at high frequency. The method has direct biotechnological
      application and provides a useful tool for basic research.

PMID- 18810647
TI  - PPAR gamma ligands, rosiglitazone and pioglitazone, inhibit bFGF- and VEGF
      mediated angiogenesis.
AB  - OBJECTIVE: To study the effect of peroxisome proliferator-activated receptor
      gamma (PPAR gamma) agonists, pioglitazone and rosiglitazone, on vascular
      endothelial growth factor (VEGF)- and basic fibroblast growth factor (bFGF)
      induced angiogenesis and on endothelial cell migration. METHODS: Chick
      chorioallantoic membrane (CAM) model was used to evaluate the efficacy of
      pioglitazone and rosiglitazone on VEGF- and bFGF-induced angiogenesis. In
      addition, the effect of pioglitazone and rosiglitazone on endothelial cell
      migration was evaluated using 8 mm pore filter to a feeder layer containing
      vitronectin as chemoattractant. RESULTS: Pioglitazone and rosiglitazone inhibited
      the pro-angiogenic effects of bFGF and VEGF in the CAM model significantly (P <
      0.001) to the same extent. Endothelial cell migration was also inhibited by both
      pioglitazone and rosiglitazone (P < 0.001). CONCLUSIONS: These results suggest
      that PPAR gamma ligands, pioglitazone and rosiglitazone, in addition to their
      important regulatory role in adipogenesis and inflammation, possess anti
      angiogenic properties. Thus, PPAR gamma ligands may be useful in the treatment of
      diabetic retinopathy, macular degeneration, and other ocular disorders and may
      lower the risk to develop cancer in diabetic patients.

PMID- 18810648
TI  - Sperm proteins in teleostean and chondrostean (sturgeon) fishes.
AB  - Sperm proteins in the seminal plasma and spermatozoa of teleostean and
      chondrostean have evolved adaptations due to the changes in the reproductive
      environment. Analysis of the composition and functions of these proteins provides
      new insights into sperm motility and fertilising abilities, thereby creating
      possibilities for improving artificial reproduction and germplasm resource
      conservation technologies (e.g. cryopreservation). Seminal plasma proteins are
      involved in the protection of spermatozoa during storage in the reproductive
      system, whereas all spermatozoa proteins contribute to the swimming and
      fertilising abilities of sperm. Compared to mammalian species, little data are
      available on fish sperm proteins and their functions. We review here the current
      state of the art in this field and focus on relevant subjects that require
      attention. Future research should concentrate on protein functions and their mode
      of action in fish species, especially on the role of spermatozoa surface proteins
      during fertilisation and on a description of sturgeon sperm proteins.

PMID- 18810649
TI  - The plasmid constructs producing shRNA corresponding to the conserved 3D
      polymerase of Foot and Mouth Disease virus protects guinea pigs against challenge
      virus.
AB  - RNA interference (RNAi) has been used as an effective antiviral strategy for its
      specific silencing of viral gene expression in mammalian cells. In this study,
      shRNA targeting two regions of Foot and Mouth Disease Virus (FMDV) i.e. 3D and
      5'UTR which are very essential in virus replication were evaluated. The
      constructs were made using h7K RNA polymerase III promoter. We investigated in
      vivo inhibitory effect of shRNA on FMDV replication in BHK-21 cells and guinea
      pigs. The results showed that transfection of 3D shRNA could reduce virus growth
      by three folds when cells were challenged with 10(2) TCID(50) of FMDV. Pretreated
      guinea pigs with 3DshRNA were protected 80% with 10(3) GPID(50) of FMDV. As a
      first report in guinea pigs which are recognized animal model for FMD vaccine
      potency testing, the study suggests that shRNA could be a viable therapeutic
      approach to control severity of FMD infection and spread.

PMID- 18810650
TI  - Early recovery of urinary continence after laparoscopic versus retropubic radical
      prostatectomy: evaluation of preoperative erectile function and nerve-sparing
      procedure as predictors.
AB  - The aim of this study was to evaluate preoperative erectile function and
      attempted nerve-sparing procedure as predictors for early recovery of urinary
      continence after retropubic and laparoscopic radical prostatectomy. Patients were
      divided into two groups according to surgical approach (retropubic or
      laparoscopic) and learning curve for laparoscopic approach: group 1--retropubic
      approach (37 patients operated on from April 2000 to June 2006), group 2-
      laparoscopic approach (109 patients operated on from April 2003 to June 2006). We
      assessed state of urinary continence at 1, 3, 6, and 12 months after removal of
      the urinary catheter. Overall rates of urinary continence were 18%, 49%, 68%, and
      80% at 1, 3, 6, and 12 months, respectively. Between groups 1 and 2, no
      statistically significant differences in recovery of urinary continence were
      evident, being 27% versus 15% at 1 month, 54% versus 47% at 3 months, 77% versus
      65% at 6 months, and 91% versus 77% at 12 months in groups 1 and 2, respectively.
      An attempted nerve-sparing procedure (one or both neurovascular bundles) was
      statistically associated with urinary continence at 3 month, and International
      Index of Erectile Function-5 (IIEF-5) score (>or=14) was identified as a
      significant factor predicting urinary continence at 6 months after laparoscopic
      radical prostatectomy. Younger age tended to result in early recovery of urinary
      continence after retropubic radical prostatectomy.

PMID- 18810651
TI  - Quantitative risk stratification and individual comprehensive therapy for
      invasive bladder cancers in China.
AB  - BACKGROUND: To evaluate the risk factors for invasive bladder cancer and to
      develop a predictive model for the improvement of individual comprehensive
      therapy for invasive bladder cancers. MATERIALS AND METHODS: The records of 356
      patients with invasive bladder cancer, operated on at three Chinese medical
      institutes, were reviewed. The Cox proportional hazards regression model was used
      to assess the clinical and pathological variables affecting disease-free survival
      (DFS). The regression coefficients determined by Cox regression analysis were
      used to construct a predictive index (PI). PI was used to categorize the patients
      into different risk groups. Kaplan-Meier survival curves followed with log-rank
      test were plotted to compare the difference. RESULTS: Tumor configuration (RR =
      1.60, P = 0.01), multiplicity (RR = 1.41, P = 0.04), histological subtype (RR =
      2.13, P < 0.01), tumor stage (RR = 2.50, P < 0.01), tumor grade (RR = 2.35, P <
      0.01), node status (RR = 2.48, P < 0.01), and neoadjuvant chemotherapy (RR =
      0.46, P = 0.02), had independent prognostic significance for DFS. PI = 0.47 x
      (configuration) + 0.34 x (multiplicity) + 0.76 x (tumor histological subtype) +
      0.92 x (stage) + 0.86 x (grade) + 0.91 x (node status) - 0.79 x (neoadjuvant
      chemotherapy). The range of PI was -0.32 to 6.52, which was equally divided into
      three risk groups with significant differences on Kaplan-Meier curves and a log
      rank test (P < 0.01). Meanwhile, the patient's probability of survival could be
      calculated by PI. CONCLUSIONS: Seven factors (tumor configuration, multiplicity,
      histological subtype, tumor stage, tumor grade, node status, neoadjuvant
      chemotherapy) affect the prognosis after radical cystectomy (RC) for invasive
      bladder cancer. PI can be used to optimize the individual comprehensive therapy.
      Given fewer perioperative complications, fast recovery from surgery and
      relatively satisfactory quality of life, ureterocutaneostomy, and ileal conduit
      are suitable for the patients with short expected life spans.

PMID- 18810652
TI  - Vesico-vaginal fistula: report of 220 cases.
AB  - OBJECTIVE: To present the major causes, diagnosis, indications, and basic
      principles of surgical treatment of vesico-vaginal fistulas (VVF). METHODS: From
      1978 to 2004, 235 surgical procedures in 220 women with vesico-vaginal fistulas
      were performed at the Clinical Center of Serbia, Urological Clinic, due to
      primary or recurrent VVF. There were 220 primary procedures: 129 transvesical
      approaches (TVES), 59 transvaginal repairs (TVAG), and 32 transperitoneal
      approaches with flap interposition (TPA). Transvesical approach was the most
      common procedure in the early period (1978-1993) and less frequent in the late
      period (1994-2004). The main causes of VVF were hysterectomy for benign
      conditions (62.7%), hysterectomy for malignant conditions (30.4%), cesarean
      section (5.9%), and obstetric injuries (0.9%). RESULTS: There was no
      perioperative mortality. There were fifteen recurrent fistula formations: twelve
      after the first operation and three after the second. The recurrence rates
      between the procedures were comparable: TVES 6.6%, TVAG 6.4%, and TPA 5.4%.
      CONCLUSIONS: The total recurrence rate of 6.4% did not differ significantly
      between various procedures. However, TVAG is less invasive and suitable for
      uncomplicated cases, whereas TPA should be recommended for great and recurrent
      VVF.

PMID- 18810653
TI  - The mechanism of acidic hydrolysis of esters explains the HDV ribozyme activity.
AB  - The hepatitis delta virus (HDV) ribozyme is an RNA enzyme that catalyzes the site
      specific trans-esterification reaction. Using high hydrostatic pressure (HHP)
      technique we showed that HDV ribozyme catalyzes the reaction of RNA cleavage in
      the absence of magnesium ions according to mechanism of acidic hydrolysis of
      esters. HHP induces changes of water structure, lowering pH and effect ribozyme
      catalytic site structure formation without magnesium. HHP, similarly to magnesium
      ion at ambient pressure stabilizes the higher order RNA structure of HDV, but
      Mg(2+) is not involved in the catalysis. Our results clearly support the new
      mechanism of HDV hydrolysis and show advantages of using HHP in analysis of
      macromolecules interaction.

PMID- 18810654
TI  - A GAL4/UAS luciferase system to identify the miRNAs target mRNAs in Drosophila S2
      cells.
AB  - MicroRNAs (miRNAs) have been shown to regulate gene expression through the
      sequence-specific base pairing with their target mRNAs. However, our
      understanding of the biological roles of miRNAs is still quite limited, and only
      a handful of miRNAs have been assigned by genetic analysis in part owing to the
      difficulty in the identification of their targets. Although computational methods
      have shown to be helpful in the prediction of miRNA targets, a major obstacle has
      been the lack of quick and efficient experimental procedures to verify these
      targets. In this report, we describe a UAS/GAL4-based reporter system for this
      purpose. Our data indicate it an assay of miRNA-target gene interaction, with
      greater sensitivity over the previously reported methods, and may be useful for
      more efficient identification/validation the miRNA targets in Drosophila cell
      lines.

PMID- 18810655
TI  - A highly significant difference in baseline characteristics: the play of chance
      or evidence of a more selective game?

PMID- 18810656
TI  - Experimental bone defect healing with xenogenic demineralized bone matrix and
      bovine fetal growth plate as a new xenograft: radiological, histopathological and
      biomechanical evaluation.
AB  - The following study was designed to evaluate xenogenic bovine demineralized bone
      matrix (DBM) and new xenograft (Bovine fetal growth plate) effects on bone
      healing process. Twenty male White New Zealand rabbits were used in this study.
      In group I (n = 10) the defect was filled by xenogenic DBM and in group II (n =
      10) the defect was filled by a segment of bovine fetal growth plate and was fixed
      by cercelage wire. Radiological, histopathological, and biomechanical evaluations
      were performed blindly and results scored and analyzed statistically. Statistical
      tests did not support significant differences between two groups radiographically
      (P > 0.05). There was a significant difference for union at the 28th
      postoperative radiologically (P < 0.05). Xenograft was superior to DBM group at
      the 28th postoperative day for radiological union (P < 0.03). Histopathological
      and biomechanical evaluation revealed no significant differences between two
      groups. In conclusion, the results of this study indicate that satisfactory
      healing occurred in rabbit radius defect filled with xenogenic bovine DBM and
      xenogenic bovine fetal growth plate. Complications were not identified and
      healing was faster in two grafting groups.

PMID- 18810657
TI  - Two sisters with Rett syndrome and non-identical paternally-derived
      microdeletions in the MECP2 gene.
AB  - The unique case of two sisters with symptoms of RTT and two quite distinct,
      novel, and apparently de novo microdeletions of the MECP2 gene is described. One
      sister possessed an 18 base-pair (bp) deletion (c.1155_1172del18) within the
      deletion hotspot region of exon 4, whereas the other sister exhibited a 43 bp
      deletion at a different location in the same exon (c.1448_1461del14+29). Although
      these lesions occurred on the same paternally-derived X chromosome, this is
      probably due to chance co-occurrence owing to the relatively high mutation rate
      of the MECP2 gene rather than to a constitutional mutator phenotype.

PMID- 18810658
TI  - Symbiosis between microorganisms from kombucha and kefir: Potential significance
      to the enhancement of kombucha function.
AB  - Gluconacetobacter sp. A4 (G. sp. A4), which had strong ability to produce d
      saccharic acid 1, 4 lactone (DSL), was the key functional bacteria isolated from
      the kombucha preserved. This paper investigated the interaction between G. sp. A4
      and ten different strains of lactic acid bacteria (LAB) obtained from kefir. The
      result suggested that the LAB promoted DSL production of G. sp. A4 to different
      extents, ranging from 4.86% to 86.70%. Symbiosis between G. sp. A4 and LAB was
      studied. LAB's metabolites, xylitol, and acetic acid, were utilized by G. sp. A4,
      and it promoted the growth of G. sp. A4 and yield of DSL. Therefore, in
      developing starter cultures for kombucha fermentation process, a mixed flora of
      LAB and G. sp. A4 would be the optimal combination.

PMID- 18810659
TI  - The transgenic BmN cells with polyhedrin gene: a potential way to improve the
      recombinant baculovirus infection per os to insect larvae.
AB  - The principle of baculovirus expression system is that substitute exogenous gene
      for polyhedrin (polh) gene, and the recombinant baculovirus lacks the ability to
      infect insect larvae by oral inoculation. In this study, we cloned the polh gene
      with immediate early gene 1 (ie1) promoter of Bombyx mori nucleopolyhedrovirus
      (BmNPV) into transposon pigA3GFP vector, transported it into BmN cells by
      lipofectamine and obtained the transgenic BmN cell line. The mRNA transcription
      of the polyhedrin gene was demonstrated by reverse transcription-polymerase chain
      reaction. Then the polh gene negative viruses (BmPAK6 and BmGFP), infected the
      transgenic BmN cells and Polyhedrin-like structures were observed in the infected
      cells. Subsequently, the viruses (vBmPAK6 and vBmGFP) from infected cells were
      used to orally inoculated the fifth instar larvae of B. mori, respectively. The
      results showed that B. mori larvae could be infected per os with the recombinant
      baculoviruses vBmPAK6 and vBmGFP, respectively. These results suggest that the
      products of polh gene expressed in the transgenic BmN cells could package the
      recombinant baculoviruses when the viruses infected the cells and raise the
      pathogenicity of the recombinant virus in orally infected B. mori larvae.

PMID- 18810660
TI  - Differentiation of PC12 cells results in enhanced VIP expression and prolonged
      rhythmic expression of clock genes.
AB  - To examine for circadian rhythmicity, the messenger RNA (mRNA) amount of the
      clock genes Per1 and Per2 was measured in undifferentiated and nerve-growth
      factor-differentiated PC12 cells harvested every fourth hour. Serum shock was
      needed to induce circadian oscillations, which in undifferentiated PC12 cultures
      lasted only one 24-h period, while in differentiated cultures, the rhythms
      continued for at least 3 days. Thus, neuronal differentiation provided PC12 cells
      the ability to maintain rhythmicity for an extended period. Both vasoactive
      intestinal polypeptide (VIP) and its receptor VPAC2 are expressed in the
      suprachiasmatic nucleus (SCN), and in agreement with VIP signaling being crucial
      for maintenance of rhythmicity, we found both VIP and VPAC2 mRNA increased after
      differentiation of PC12 cells. Pituitary adenylate cyclase activating polypeptide
      (PACAP) exerts time- and concentration-dependent effects on Per gene expression
      in the SCN. We added 1 nM and 1 microM PACAP to oscillating PC12 cells at times
      corresponding to midday and early and late night to evaluate whether the effects
      were similar as in SCN. Induction of Per1 mRNA was found at all three times,
      which differs from results in SCN. Thus, PC12 cells seem more useful for studying
      mechanisms behind acquirement of rhythmicity of cell cultures than for resetting
      of circadian rhythm.

PMID- 18810661
TI  - Metaanalysis of tirilazad mesylate in patients with aneurysmal subarachnoid
      hemorrhage.
AB  - BACKGROUND: Tirilazad is a non-glucocorticoid, 21-aminosteriod that inhibits
      lipid peroxidation. It had neuroprotective effects in experimental ischemic
      stroke and reduced angiographic vasospasm after experimental subarachnoid
      hemorrhage (SAH). Five randomized clinical trials of tirilazad were conducted in
      patients with SAH. We performed a meta-analysis of these trials to assess the
      effect of tirilazad on unfavorable outcome, symptomatic vasospasm, and cerebral
      infarction after SAH. METHODS: Data from 3,797 patients were analyzed and modeled
      using random effect and Mantel-Haenszel meta-analyses and multivariable logistic
      regression to determine the effect of tirilazad on clinical outcome, symptomatic
      vasospasm, and cerebral infarction. Clinical outcome was assessed 3 months after
      SAH using the Glasgow outcome scale, and symptomatic vasospasm was defined by
      clinical criteria with laboratory and radiological exclusion of other causes of
      neurological deterioration. RESULTS: The five trials were randomized, double
      blind, and placebo-controlled. Tirilazad did not significantly decrease
      unfavorable clinical outcome on the GOS (odds ratio [OR] 1.04, 95% confidence
      interval [CI] 0.89-1.20) or cerebral infarction (OR 1.04, 95% CI 0.89-1.22).
      There was a significant reduction in symptomatic vasospasm in patients treated
      with tirilazad (OR 0.80, 95% CI 0.69-0.93). There was no heterogeneity across the
      five trials. CONCLUSION: Tirilazad had no effect on clinical outcome but did
      decrease symptomatic vasospasm in five trials of aneurysmal SAH. The dissociation
      between clinical outcome and symptomatic vasospasm deserves further
      investigation.

PMID- 18810662
TI  - On our way to evidence-based medicine: impact of a neurointensive team on stroke
      outcomes.

PMID- 18810663
TI  - The role of non-invasive ventilation and factors predicting extubation outcome in
      myasthenic crisis.
AB  - INTRODUCTION: Myasthenic crisis is a great threat to patients with myasthenia
      gravis. Usage of non-invasive ventilation (NIV) to prevent intubation and timing
      of extubating of patients in myasthenic crisis are important issues though not
      well documented. METHODS: To explore the factors predicting NIV success and
      extubation outcome in myasthenic crisis, we reviewed the records of 41 episodes
      of myasthenia crisis. RESULTS: NIV was applied to 14 episodes of myasthenic
      crisis and eight (57.1%) of them were successfully prevented from intubation. An
      Acute Physiology and Chronic Health Evaluation (APACHE) II score of <6 and a
      serum bicarbonate level of <30 mmol/l were independent predictors of NIV success.
      For patients undergoing invasive mechanical ventilation, extubation failure was
      observed in 13 (39.4%) of 33 episodes, and the most common cause was sputum
      impaction due to a poor cough strength (61.5%). A maximal expiratory pressure
      (Pemax) of > or = 40 cmH(2)O was a good predictor of extubation success.
      Extubation failure led to poorer outcomes. CONCLUSIONS: NIV may be applied to
      those patients with a low APACHE II score and a lesser degree of metabolic
      compensation for respiratory acidosis. For patients undergoing invasive
      mechanical ventilation, extubation failure is associated with significant in
      hospital morbidity in myasthenic crisis. Adequate levels of Pemax and cough
      strength correlate significantly with extubation success.

PMID- 18810664
TI  - Implications of early versus late bilateral pulmonary infiltrates in patients
      with aneurysmal subarachnoid hemorrhage.
AB  - INTRODUCTION: Bilateral pulmonary infiltrates occur frequently following
      aneurysmal subarachnoid hemorrhage (SAH), and may be associated with worse
      outcomes. The etiology, natural history, and prognosis of infiltrates occurring
      soon after SAH may differ from the characteristics of infiltrates developing at a
      later time. METHODS: We performed a retrospective cohort study involving 245
      consecutive patients with a ruptured cerebral aneurysm to assess the association
      between "early" (< or = 72 h) or "late" (>72 h) bilateral pulmonary infiltrates
      and subsequent death or neurologic impairment. We used logistic regression models
      to adjust for baseline differences in age, level of consciousness, amount of
      blood on computed tomography, and the presence or absence of clinical vasospasm.
      RESULTS: Sixty-seven patients (27%) developed bilateral pulmonary infiltrates. Of
      these, 36 (54%) had early infiltrates, 24 (36%) had late infiltrates, and 7 (10%)
      had both. Twenty-eight patients (11% of entire cohort) met criteria for acute
      respiratory distress syndrome (ARDS). Patients with early infiltrates were more
      likely to have presented with stupor or coma than patients who developed
      infiltrates later (64% vs. 29%, P < 0.01). In multivariable analysis, late
      pulmonary infiltrates were strongly predictive of poor outcome (OR 5.0, 95% CI
      1.9-13.6, P < 0.01), while early infiltrates were not (OR 1.2, 95% CI 0.5-3.0, P
      = 0.66). CONCLUSIONS: Bilateral pulmonary infiltrates after SAH most often occur
      within three days of aneurysm rupture. However, only infiltrates occurring beyond
      this time are independently associated with poor outcome. Increased emphasis on
      the prevention of late pulmonary complications has the potential to improve
      outcomes in SAH.

PMID- 18810665
TI  - Concurrent neurocysticercosis and pulmonary tuberculosis.
AB  - OBJECTIVE: We discuss the case of a 24-year-old male with severe racemose
      neurocysticercosis. CLINICAL FEATURES: The patient presented from an outside
      hospital with 4 months duration of intermittent syncope and a dull occipital
      headache with greatest severity in the morning. He was noted to have left facial
      numbness and blurred vision confined to his left eye. Magnetic resonance imaging
      (MRI) discovered multiple grape-like cystic structures throughout the
      subarachnoid space and frontal parenchyma consistent with neurocysticercosis.
      Additional testing revealed radiologic and culture evidence of active pulmonary
      tuberculosis. INTERVENTIONS AND OUTCOME: The patient was admitted to the
      neurocritical care unit and begun on IV corticosteroids, albendazole, and 4-drug
      RIPE therapy. Improvement in headache, facial numbness, and nausea were noted
      over the course of 1 week. Visual acuity remained impaired; however, no further
      episodes of syncope or deterioration were noted. CONCLUSION: Effective management
      of severe racemose neurocysticercosis requires appropriate diagnostic
      considerations, monitoring, and therapeutics well suited to a comprehensive
      neurocritical care unit.

PMID- 18810666
TI  - Cardiogenic shock with stunned myocardium during triple-H therapy treated with
      intra-aortic balloon pump counterpulsation.
AB  - INTRODUCTION: Excessive use of adrenergic agents may result in stunned
      myocardium. CASES: We report the cases of two patients with subarachnoid
      hemorrhage (SAH) complicated by cardiogenic shock secondary to triple-H therapy
      for cerebral vasospasm. Both patients had normal cardiac function on admission
      and no signs of acute myocardial infarction at the onset of cardiogenic shock.
      Intra-aortic balloon pump (IABP) counterpulsation was used to maintain adequate
      cerebral perfusion while enabling the high doses of norepinephrine that were
      being administered to be reduced. Reversal of the myocardial dysfunction after
      vasopressors were discontinued supported a diagnosis of catecholamine-induced
      stunned myocardium. CONCLUSION: IABP counterpulsation may be one therapeutic
      option for patients with vasospasm after SAH when high doses of vasopressors can
      induce severe myocardial dysfunction. However, this invasive device may not be
      sufficient to maintain adequate cerebral perfusion and fatal embolic events can
      complicate the clinical course.

PMID- 18810667
TI  - Risk of thromboembolism following acute intracerebral hemorrhage.
AB  - INTRODUCTION: Intracerebral hemorrhage (ICH) is the most feared complication of
      oral anticoagulant therapy (OAT). While anticoagulated patients have increased
      severity of bleeding following ICH, they may also be at increased risk for
      thromboembolic events (TEs) given that they had been prescribed OAT prior to
      their ICH. We hypothesized that TEs are relatively common following ICH, and that
      anticoagulated patients are at higher risk for these complications. METHODS:
      Consecutive patients with primary ICH presenting to a tertiary care hospital from
      1994 to 2006 were prospectively characterized and followed. Hospital records were
      retrospectively reviewed for clinically relevant in-hospital TEs and patients
      were prospectively followed for 90 day mortality. RESULTS: For 988 patients of
      whom 218 (22%) were on OAT at presentation, median hospital length of stay was 7
      (IQR 4-13) days and 90-day mortality was 36%. TEs were diagnosed in 71 patients
      (7.2%) including pulmonary embolism (1.8%), deep venous thrombosis (1.1%),
      myocardial ischemia (1.6%), and cerebrovascular ischemia (3.0%). Mean time to
      event was 8.4 +/- 7.0 days. Rates of TE were 5% among those with OAT-related ICH
      and 8% among those with non-OAT ICH (P = 0.2). After multivariable Cox
      regression, the only independent risk factor for developing a TE was external
      ventricular drain placement (HR 2.1, 95% CI 1.1-4.1, P = 0.03). TEs had no effect
      on 90-day mortality (HR 0.7, 95% CI 0.5-1.1, P = 0.1). CONCLUSIONS: The incidence
      of TEs in an unselected ICH population was 7.2%. Patients with OAT-related ICH
      were not at increased risk of TEs.

PMID- 18810668
TI  - Palliative surgical bypass for pancreatic and peri-ampullary cancers.
AB  - BACKGROUND: The optimal method of palliation for patients with unresectable
      pancreatic and peri-ampullary cancer (PAC) is controversial with surgical bypass
      or endoscopic stenting, each having advantages and disadvantages. AIMS: We
      analysed short term outcomes and survival for all patients undergoing surgical
      palliative bypass procedures. MATERIALS AND METHODS: All patients undergoing
      palliative surgical bypass for unresectable PAC from Aug 1999 to July 2007 were
      identified from our database. Outcomes analysed were peri-operative morbidity,
      mortality, and overall survival with comparisons from contemporaneous literature.
      RESULTS: One hundred eight patients (median age 65 (range 36-86) years; male =
      61) had palliative surgical bypass procedures for unresectable PAC. Patients
      underwent combined biliary and gastric bypass (n = 81, 75%), gastric bypass alone
      (n = 24, 22.2%) or biliary bypass alone (n = 3, 2.8%). Overall mortality was 6.5%
      and the morbidity was 15.7%. Median hospital stay was 11 (range 4-54) days.
      Median survival was 6 (95% confidence interval (CI) = 4.3-7.6) months. No re
      explorations for recurrent biliary or gastric obstruction were required.
      Contemporaneous literature review showed similar results. CONCLUSION: Surgical
      bypass performed in a specialist pancreatic center can offer effective palliation
      for unresectable PAC, with satisfactory outcomes.

PMID- 18810669
TI  - Whole-tumor-antigen-pulsed dendritic cells elicit cytotoxic T-cell response
      against pediatric nasopharyngeal carcinoma in vitro.
AB  - Nasopharyngeal carcinoma (NPC) is endemic in Southeast Asia. Although dendritic
      cell (DC)-based vaccine has emerged as a promising immunotherapy for various
      malignancies, its use in pediatric nasopharyngeal carcinoma (PNPC) has not been
      addressed. In this study, DCs isolated from peripheral blood monocytes of three
      pediatric patients with advanced (stage IV) NPC were incubated with whole-tumor
      antigen preparations and differentiated into immature DCs in the presence of
      granulocyte-macrophage colony-stimulating factor and interleukin-4, and then
      underwent maturation when exposed to tumor necrosis factor-alpha. Upon
      maturation, DCs acquired the ability to stimulate T-cell proliferation as
      examined by [(3)H]-thymidine incorporation and the ability of these T-cells to
      secrete interferon-gamma as determined by enzyme-linked immunosorbent spot assay.
      Cytotoxic assay revealed that mature tumor-antigen-pulsed DCs induced cytotoxic
      activity of the T-cells against both autologous and allogeneic NPC tumor cells
      (including NPC tumor cells from a different individual or from CNE-2Z, a poorly
      differentiated human NPC cell line). Blocking HLA class I molecules by W6/32
      inhibited T-cell-mediated cytotoxic activity in both autologous and allogeneic
      settings. Our results indicate that DCs pulsed with whole-tumor-antigen can
      effectively activate HLA class I-restricted cytotoxic T-cells in vitro, and thus
      provide experimental basis for their future clinical use in PNPC.

PMID- 18810670
TI  - Herbal preparation of realgar induces acute renal failure.

PMID- 18810671
TI  - [2008 presidential editorial].

PMID- 18810672
TI  - Probiotic Escherichia coli Nissle 1917 (EcN) for successful remission maintenance
      of ulcerative colitis in children and adolescents: an open-label pilot study.
AB  - Since about 20 % of patients with ulcerative colitis (UC) are children and
      adolescents there is a need for therapeutic options custom-tailored to the
      children's needs. E. coli Nissle 1917 (EcN) as an evidence-based probiotic
      alternative to mesalazine (5-ASA) in adult UC remission maintenance is a
      promising agent for such a therapy. The present open-labelled pilot study was
      undertaken to investigate the clinical benefit of EcN for maintenance therapy in
      young UC patients. 34 patients with UC in remission aged between 11 and 18 years
      were allocated either to EcN (2 capsules o. d., n = 24) or 5-ASA (median 1.5 g/d,
      n = 10) and observed over one year. As a result, the relapse rate was 25 % (6 /
      24) in the EcN group and 30 % (3 / 10) in the 5-ASA group. Data on the patients'
      global health and development were favourable and no serious adverse events were
      reported. In conclusion, maintenance therapy for UC with the probiotic EcN is
      effective also in young patients.

PMID- 18810673
TI  - [An unusual cause of severe abdominal pain].
AB  - A 33-year-old previously healthy man was admitted to the hospital with a 6-day
      history of diffuse abdominal pain and constipation. He was afebrile, looked
      unwell with a pale skin and displayed an elevated blood pressure. He had no
      peritoneal sign, and bowel sounds were normal. Blood tests were remarkable for a
      hematocrit of 26 % and mean cell volume of 83 fl, bilirubin levels were slightly
      elevated. Abdominal radiographs, abdominal ultrasound and computed tomography
      showed stool throughout the colon with a non-specific bowel gas pattern.
      Moreover, colonoscopy and gastroscopy provided no information on the underlying
      cause of the patient's severe pain. He was treated with fluids and spasmolytic
      drugs until the result of the urinary porphyrin level was received, which showed
      an elevated concentration of 1608 microg/d. Consequently, the plasma lead
      concentration was determined showing an elevated level of 92.3 microg/d. The
      examination of blood slides revealed erythrocytes with basophile stippling. On
      physical examination, a bluish discoloration could be seen along the gums. After
      starting the detoxication therapy with DMPS - 1800 mg p. o. for the first two
      days followed by 600 mg DMPS daily - the complaints disappeared. In spite of an
      extensive anamnestic exploration the source of the lead intoxication could not be
      found until now.

PMID- 18810674
TI  - Pneumococcal meningitis during antiviral treatment with interferon and ribavirin
      in a splenectomized patient with chronic hepatitis C - do not miss vaccination
      before starting therapy.
AB  - We report on a 35-year-old man who developed pneumococcal meningitis while
      receiving antiviral therapy with interferon (consensus interferon, CIFN) and
      ribavirin for chronic hepatitis C. Antibiotic therapy was started four days after
      the onset of symptoms. Unfortunately, the patient developed a persisting right
      sided cochlear hearing impairment. Antiviral therapy led to sustained viral
      response of hepatitis C. At the age of 14 years he had experienced a hemorrhagic
      shock after a traffic accident, received multiple blood transfusions and
      undergone a splenectomy. He had not received vaccination against Streptococcus
      pneumoniae. This case report reminds us that splenectomized patients without
      previous pneumococcal vaccination should receive such vaccination before
      immunomodulatory treatment.

PMID- 18810675
TI  - [Functional ultrasound in gastroenterology].
AB  - Ultrasonography has become increasingly important in the routine diagnostics of
      gastrointestinal diseases. It is first of all a morphological diagnostic method.
      As it not only assesses the wall structure of the gallbladder, the pancreatic
      duct and the whole gastrointestinal tract but also visualises motion sequences as
      a real-time-method, functional processes and their disruptions can especially be
      examined. The present authors give a review of the capacity of functional
      ultrasound in different anatomic zones and critically discuss its practical
      relevance.

PMID- 18810676
TI  - [Endoscopic ultrasound-guided biopsy: diagnostic yield, pitfalls, quality
      management].
AB  - The differential diagnosis of tumorous lesions in the pancreas, liver, adrenal
      gland or lymph nodes is ambiguous. Specific tissue diagnoses are essential for
      treatment decisions. Endoscopic ultrasound-guided biopsy has proven to be a
      reliable and effective modality in obtaining samples for cytological or
      histological examinations either primarily or in cases in which other biopsy
      techniques have failed. The reproducibility of cytopathological diagnoses among
      pathologists with special experience in assessing material obtained by endoscopic
      ultrasound-guided biopsies is very high. False positive diagnoses of malignancy
      in endoscopic ultrasound-guided biopsy are rare; false negative diagnoses appear
      in a variable frequency depending on target tissue, technical factors, and
      expertise of the endosonographer and cytopathologist. There are numerous
      challenges and pitfalls in the differential diagnostic classification of benign
      and malignant lesions. These problems are related to the characteristics of
      samples obtained by endoscopic ultrasound-guided biopsy, as well as to the
      multiple diagnoses with similar or overlapping cytological or histological
      characteristics. This review discusses the performance of endoscopic ultrasound
      guided biopsy in establishing specific tissue diagnoses, possible pitfalls as
      well as opportunities to minimise differential diagnostic errors.

PMID- 18810677
TI  - [Miniprobe EUS].
AB  - With the advent of flexible, high-frequency catheter probes that can be
      introduced through the working channel of any endoscope, EUS became available as
      an additional and very powerful diagnostic tool during routine endoscopic
      procedures. Miniprobes as a supplement to echoendoscopes with radial or
      longitudinal scanners provide detailed images with a penetration depth of about
      20 mm using frequencies of around 20 MHz. Not only structures of the intestinal
      wall but also a considerable volume of the surrounding organs can be visualised.
      In the intestine sonographic coupling is best accomplished using bare miniprobes
      with water filling of the lumen. Out of 1007 miniprobe examinations carried out
      in the author's clinic, the most frequent indications involved the distal bile
      and pancreatic ducts (36 %), carcinoma of the oesophagus or the cardia (18 %),
      submucosal tumours and GIST (14 %), and others (32 %). For evaluating the distal
      common bile duct, extraductal EUS (EDUS) allows the visualisation of small
      pathological lesions, especially intraductal stones without ductal dilatation
      with a sensitivity of 97 % and a specificity of 98 %. For the staging of early
      cancers, miniprobe EUS has its significance mainly in showing a preserved
      submucosal layer, thereby excluding an endoscopically non-resectable T 2 lesion,
      as was successfully done in all of our cases. Suspicious prominent structures
      were easily assigned to the correct layer of the wall or identified as external
      impressions.

PMID- 18810678
TI  - [News from the cochrane library: mu opioid antagonists for opioid-induced bowel
      dysfunction].
AB  - Constipation and other gastrointestinal symptoms are frequent adverse effects of
      either short-term postoperative or chronic opioid therapy. The review authors
      have identified 23 studies to evaluate the efficacy of micro-opioid antagonists
      for the prevention and treatment of these complications. The data on safety and
      efficacy of the traditional antagonists naloxone and nalbuphine are insufficient.
      The results of studies with the newer, peripherally-acting antagonists alvimopan
      and methylnaltrexone are promising. Methylnaltrexone resulted in four studies
      with healthy probands in a significant shortening of the gastrointestinal transit
      time (-52 min). In the postoperative setting, five studies showed a significant
      improvement of the hazard ratios for different outcomes (e. g., bowel movement,
      tolerance of solid food) in the alvimopan group. Future studies will be needed to
      show whether these results can be reproduced in different patient groups on a
      larger scale. Also, with regard to other pharmacological (e. g., lactulose) and
      non-pharmacological interventions, the role of the above-mentioned not yet
      approved medications needs to be defined.

PMID- 18810679
TI  - [Clinical practice guideline on diagnosis and treatment of Crohn's disease].

PMID- 18810680
TI  - Tuberculosis.

PMID- 18810681
TI  - Lessons from molecular epidemiology and comparative genomics.
AB  - Molecular biology has revolutionized the field of tuberculosis (TB) research.
      Comparative genomics and molecular epidemiology are providing revelations about
      the evolutionary origins of MYCOBACTERIUM TUBERCULOSIS and phylogenetic
      relationships between different strains and strain families. Accumulating
      evidence indicates that distinct strains of M. TUBERCULOSIS (genotype) may be
      associated with differential transmissibility, virulence, and/or clinical
      manifestations (phenotype). As advances in our understanding of the relationships
      between genotype and phenotype progress, this knowledge will have important
      ramifications for TB control and the development of novel vaccines and improved
      diagnostics. Some of the greatest advantages of molecular epidemiological methods
      include our abilities to follow transmission of particular strains within
      communities, track epidemics, and recognize the presence of historic outbreaks.
      Moreover, there are critical questions about TB that are essentially unanswerable
      in the absence of molecular techniques. These include our capacity to distinguish
      exogenous reinfection from endogenous reactivation in recurrent TB cases and to
      recognize primary transmission of drug resistant strains versus the acquisition
      of drug resistance via de novo mutations. Finally, an elucidation of the
      phylogenetic structure and evolutionary history of M. TUBERCULOSIS provides a
      necessary background for understanding the underlying mechanisms responsible for
      the continued success of this deadly pathogen.

PMID- 18810682
TI  - Global epidemiology of tuberculosis: prospects for control.
AB  - The burden of tuberculosis (TB) is now very slowly decreasing globally. However,
      the rate of decline is too slow to reach all the epidemiological impact targets
      set for 2015. The prospects for reaching the TB elimination target set for 2050
      are even bleaker. Implementation of the World Health Organization's Stop TB
      Strategy is currently lagging behind the envisioned scale-up pace, particularly
      with regard to TB/HIV collaborative activities and management of drug resistant
      TB. To ensure long-term TB control there is, first, a need to ensure that all
      components of the Stop TB Strategy are scaled up according to plans, with special
      attention to improved access for the poor. However, this may not be enough.
      Recent analyses suggest that the impact of current efforts to reduce TB incidence
      is less than expected and that improved diagnostic and curative efforts need to
      be combined with additional preventive efforts. New and more effective vaccines
      and drugs for preventive treatment would revolutionize TB control. A stronger
      focus on prevention would also entail more concerted actions to limit the impact
      of TB risk factors, including HIV/AIDS, smoking, malnutrition, alcoholism,
      diabetes, crowded living conditions, and indoor air pollution, which may all
      contribute a considerable proportion of the global TB burden.

PMID- 18810683
TI  - The epidemiology of tuberculosis in the United States.
AB  - Effective control of tuberculosis (TB) requires an understanding of the changing
      epidemiology of the disease. An understanding of the epidemiology is needed for
      public health departments to respond with appropriate program-planning decisions.
      Following a marked decline in the incidence of tuberculosis in the United States
      over several decades, the incidence escalated dramatically and peaked in 1992.
      The resurgence of TB reflected several factors, including deteriorating social
      conditions, dismantling of the public health infrastructure, dwindling support
      for tuberculosis clinics and services, the new epidemic of HIV/AIDS with highly
      susceptible individuals at risk, and immigration of individuals from countries
      with high rates of TB. Since 1992, there has been a substantial decline in new
      cases. The success in reducing the tuberculosis burden reflects several factors,
      including improved public health efforts, physician and patient education,
      infection control measures, and the use of directly observed therapy (DOT). By
      2006, cases of TB in the United States had reached historic lows. Currently, a
      majority of cases of TB occur in foreign-born individuals, reflecting immigration
      from countries with high endemic rates of TB. Future efforts to curtail the
      incidence of TB will require vigilant public health efforts, improving education
      of patients and health care personnel, identifying mechanisms and routes of
      transmission, and assuring adequate treatment and prophylactic regimens among
      infected individuals.

PMID- 18810685
TI  - HIV-associated tuberculosis: diagnostic and treatment challenges.
AB  - Tuberculosis (TB) and the human immunodeficiency virus (HIV) are, individually,
      two of the world's greatest ongoing public health threats. In combination, the
      two diseases can be even more devastating. HIV significantly increases an
      individual's chances of reactivation of latent TB infection and progression to
      active TB disease. HIV's associated immunosuppression makes it more difficult to
      diagnose active TB due to a higher likelihood of atypical and extrapulmonary
      presentation and poorer performance of standard diagnostic tools. TB is the major
      cause of death in individuals infected with HIV, and the combination of both
      illnesses creates unique treatment challenges for providers due to interactions
      between antituberculous and antiretroviral medications, overlapping drug
      toxicities, and the immune reconstitution inflammatory syndrome. Magnifying these
      challenges even further is the fact that much of the burden of TB/HIV coinfection
      exists in some of the world's most resource-limited settings. Concerted efforts
      are needed to identify rapid and accurate diagnostic tools for active TB disease
      and latent TB infection (LTBI) that are practical and inexpensive and that
      perform well in individuals with HIV infection. Also needed are effective and
      feasible strategies to optimize management of both conditions in the coinfected
      patient.

PMID- 18810684
TI  - Epidemiology and treatment of multidrug resistant tuberculosis.
AB  - Multidrug resistant tuberculosis is now thought to afflict between 1 and 2
      million patients annually. Although significant regional variability in the
      distribution of disease has been recorded, surveillance data are limited by
      several factors. The true burden of disease is likely underestimated.
      Nevertheless, the estimated burden is substantial enough to warrant concerted
      action. A range of approaches is possible, but all appropriate interventions
      require scale-up of laboratories and early treatment with regimens containing a
      sufficient number of second-line drugs. Ambulatory treatment for most patients,
      and improved infection control, can facilitate scale-up with decreased risk of
      nosocomial transmission. Several obstacles have been considered to preclude
      worldwide scale-up of treatment, mostly attributable to inadequate human, drug,
      and financial resources. Further delays in scale-up, however, risk continued
      generation and transmission of resistant tuberculosis, as well as associated
      morbidity and mortality.

PMID- 18810686
TI  - New approaches to the treatment of latent tuberculosis.
AB  - It is estimated that one third of the global population is infected with
      MYCOBACTERIUM TUBERCULOSIS. Treatment of M. TUBERCULOSIS infection is an
      important strategy for tuberculosis elimination, but the effectiveness of this
      strategy is limited by poor adherence to therapy, which is due at least in part
      to the long duration of treatment. A 9-month course of isoniazid is the currently
      preferred treatment regimen for M. TUBERCULOSIS infection, due to the extensive
      data regarding the effectiveness and tolerability of isoniazid, and limited data
      on the effectiveness and tolerability of alternative shorter-course regimens.
      This review covers all currently available regimens, including less established
      alternative treatment regimens (e.g., rifampin for 4 months and isoniazid +
      rifampin for 3 months), as well as regimens that are currently under
      investigation (e.g., isoniazid + rifapentine for 3 months). Potential future
      regimens and experimental approaches are also discussed.

PMID- 18810687
TI  - Using animal models to develop new treatments for tuberculosis.
AB  - Animal models have an important role in the preclinical evaluation of new
      antituberculosis drug candidates. Although it does not recapitulate the
      clinicopathological manifestations of tuberculosis in humans, the mouse remains
      the best characterized and most economical animal model for experimental
      chemotherapy. Provided care is taken to optimize the experimental conditions, the
      mouse has produced reliable data on the bactericidal and sterilizing activity of
      existing antituberculosis drugs and informed numerous clinical trials. Still,
      other animal models, especially the guinea pig, may have utility as confirmatory,
      or even alternative, models under certain circumstances. This chapter reviews
      some of the important considerations when selecting an animal model and presents
      a model for the sequential evaluation of a new compound with promising
      antituberculosis activity.

PMID- 18810688
TI  - Emerging drugs for active tuberculosis.
AB  - Tuberculosis (TB) drug research and development lay largely fallow from the 1960s
      to the turn of the century. A realization that current treatments for this major
      public health epidemic are proving inadequate to control the disease and prevent
      development and spread of drug resistance has stimulated renewed activity during
      the past 5 to 10 years. As a result, there are now seven drugs in clinical
      development for TB and many groups working on discovery-stage projects. This
      article summarizes the published information available on the seven clinical
      candidates and describes some of the challenges faced by those pursuing research
      and development of novel TB therapies.

PMID- 18810689
TI  - New diagnostics for latent and active tuberculosis: state of the art and future
      prospects.
AB  - Tuberculosis (TB) continues to be the world's most important infectious cause of
      morbidity and mortality among adults. Nearly 9 million people develop TB disease
      each year, and an estimated 1.6 million die from the disease. Despite this
      enormous global burden, case detection rates are low, posing serious hurdles for
      TB control. Conventional TB diagnosis continues to rely on antiquated tests such
      as sputum smear microscopy, culture, tuberculin skin test, and chest radiography.
      These tests have several limitations and perform poorly in populations affected
      by the HIV epidemic. Conventional tests for detection of drug resistance are time
      consuming, tedious, and inaccessible in most settings. In this review, we
      describe recent advances in the diagnosis of latent and active TB, and detection
      of drug resistance. Although the perfect test will not be ready for large-scale
      roll-out and integration into routine TB care services for some time, substantial
      progress has been made in expanding the TB diagnostic product pipeline. With the
      resurgence of interest in the development of new tools for TB control, and the
      recent influx of funding and political support, it is likely that the next few
      years will see the introduction of new diagnostic tools into routine TB control
      programs.

PMID- 18810690
TI  - Diagnosis and treatment of infections due to Mycobacterium avium complex.
AB  - MYCOBACTERIUM AVIUM complex (MAC) consists of nontuberculous mycobacteria that
      cause disease in immunocompromised and immunocompetent hosts. The organisms are
      ubiquitous in the environment, and acquisition occurs through ingestion or
      inhalation of aerosols from soil, water, or biofilms. Disease may manifest as
      disseminated infection, soft tissue infection, chronic pneumonia, or
      hypersensitivity pneumonitis. Nontuberculous mycobacteria are increasingly
      associated with pulmonary disease, with MAC being the most common nontuberculous
      mycobacteria to cause pulmonary disease in the United States. Pulmonary symptoms,
      nodular or cavitary opacities on a chest radiograph or high-resolution computed
      tomographic scan with multifocal bronchiectasis and multiple small nodules, plus
      positive culture results from two sputum specimens or one bronchoscopic specimen
      are consistent with MAC pulmonary disease. Treatment consists of a macrolide,
      rifamycin, and ethambutol given three times weekly for noncavitary disease and
      daily with or without an aminoglycoside for cavitary disease.

PMID- 18810691
TI  - Diagnosis and treatment of infections caused by rapidly growing mycobacteria.
AB  - Rapidly growing mycobacteria (RGM) are ubiquitous environmental organisms capable
      of causing a wide variety of infections in humans. The prevalence of RGM
      infections appears to be increasing, although exact incidence rates are unknown.
      Although some risk factors for pulmonary RGM infection have been determined, the
      specific host factors predisposing to disease in the majority of cases are not
      clear. Significant advances in molecular methods of mycobacterial identification
      have led to isolation of more varieties, changes in taxonomy, and more rapid and
      accurate diagnosis of RGM from clinical isolates. Despite significant advances in
      the field, diagnosing and treating RGM pulmonary infections remain complicated.
      Current guidelines are based on the most commonly encountered NTM. Their
      applicability to less frequent RGM isolates has not been definitively
      established. Treatment often requires multiple antimicrobial agents for prolonged
      periods of time, with varying degrees of success and significant associated
      morbidity.

PMID- 18810693
TI  - Inotropic, vasodilating and preconditioning actions of levosimendan in the heart.
AB  - BACKGROUND: Levosimendan improves ventricular function, induces vasodilation and
      induces myocardial preconditioning. We determined the external efficiency and
      assessed the effects on arrhythmias. METHODS: In isolated, blood-perfused rabbit
      hearts, levosimendan (0.75 micromol) or placebo was administered, while
      hemodynamics were recorded. After no-flow ischemia and reperfusion, data were
      recorded again. RESULTS: Placebo in normoxic hearts did not affect measurements,
      while levosimendan increased heart rate (+ 18 %) and improved coronary output (+
      52 %), stroke volume (+ 28 %), maximal left ventricular pressure (+ 30 %),
      maximal rate of pressure increase (+ 36 %), work (+ 68 %), minimal rate of
      pressure increase (+ 53 %), coronary blood flow (+ 41 %), coronary resistance (-
      19 %) and external efficiency (33 %; P < 0.05). During reperfusion, hemodynamics
      in the levosimendan group were significantly better preserved compared with the
      placebo group. Early reperfusion arrhythmias were decreased (levosimendan group:
      7 +/- 3 % vs. placebo group: 25 +/- 17 %; P < 0.05). CONCLUSIONS: Levosimendan
      does not impair diastole, dilates coronary vessels, induces pharmacological
      preconditioning, improves external efficiency and exerts antiarrhythmic
      properties during reperfusion. As this drug protects the heart from reperfusion
      injury, it seems well suited for treating dysfunctional hearts after cardiac
      surgery.

PMID- 18810694
TI  - Early and late results of permanent atrial fibrillation ablation surgery in
      aortic valve and CABG patients.
AB  - OBJECTIVE: The study investigates the early and late results of permanent atrial
      fibrillation (AF) ablation surgery concomitant to coronary artery bypass grafting
      (CABG) and/or aortic valve (AV) surgery. METHODS: Between February 2001 and April
      2006, a selective group of 80 patients with permanent AF (median: 48 months
      [Perc25/75 24/110; range: 6 - 360 months]) underwent either bipolar (n = 60) or
      monopolar (n = 20) radiofrequency (RF) ablation procedures concomitant to CABG
      and/or AV surgery (CABG: n = 39; AV: n = 30; AV + CABG: n = 11). All patients
      were restudied to assess survival, conversion rate to stable sinus rhythm (SR)
      and New York Heart Association (NYHA) class early (3 +/- 1 months) and late after
      surgery (30 +/- 15 months). Data were analyzed exploratively. RESULTS: Survival
      at 3 and 30 months was 98 % and 96 %, respectively. Stable SR could be documented
      in 73 % and 77 % of patients. Long-term AF before surgery and larger LA size were
      predictive for AF return after surgery ( P = 0.004 and P = 0.032, respectively).
      Neither age, gender, the application modus of the RF energy nor the underlying
      cardiac disease influenced the postoperative cardiac rhythm significantly. NYHA
      class improved significantly after surgery ( P < 0.0005), particularly when
      stable SR was achieved ( P = 0.049). CONCLUSION: Preoperative permanent AF
      duration time and larger LA size are useful variables to predict the success rate
      of concomitant ablation surgery in CABG and/or AV patients. Further it could be
      demonstrated that established SR remained stable over time.

PMID- 18810695
TI  - Outcome after surgical repair/palliation of congenitally corrected transposition
      of the great arteries.
AB  - BACKGROUND: The surgical concepts for patients with congenitally corrected
      transposition of the great arteries (CCTGA) address discordant connections and
      associated lesions. The outcomes after biventricular repair without correction of
      discordant connections ("classic repair", or with its correction "anatomic
      repair") and after "univentricular palliation" were investigated. METHODS: All
      patients with CCTGA who underwent "classic repair" (n = 39), "anatomic repair" (n
      = 6), or "univentricular palliation" (n = 11) between 1978 and 2006 were
      analyzed. The most frequently associated lesions were ventricular septal defect
      (n = 48), tricuspid insufficiency (TI) (n = 20) and functionally single ventricle
      (n = 11). RESULTS: Thirty-day mortality was 4 % (2/56). Mean follow-up for early
      survivors was 7.2 +/- 7.1 years. Eight patients died late, two after heart
      transplantation. Survival was not significantly different between patients who
      underwent "anatomic" or "classic repair", or "univentricular palliation": 83.3 +/
      15.2 %, 79.7 +/- 6.9 %, 90.9 +/- 8.7 % at 10 years, respectively. In
      multivariate analysis, the presence of TI emerged as the only risk factor for
      late death ( P = 0.004). Twenty patients required reoperation, mainly for TI (n =
      10) and conduit failure (n = 6). Freedom from reoperation was lower after
      "anatomic repair", but ventricular function was better and atrioventricular
      valves were more competent than after "classic repair". CONCLUSIONS:
      Biventricular "anatomic" or "classic repair" and "univentricular palliation"
      yield equivalent survival rates in the mid-term. Biventricular "anatomic repair",
      when feasible, should be promoted because of its better long-term outcome.

PMID- 18810696
TI  - A staged approach towards interventional aortic valve implantation with a
      sutureless valve: initial human implants.
AB  - OBJECTIVE: Percutaneous implantable aortic valves may become an alternative to
      conventional approaches. The purpose of this study was to assess a new sutureless
      aortic valve (Perceval Sorin). As a first step, an open approach using
      cardiopulmonary bypass (CPB) was chosen to evaluate the feasibility of
      implantation. METHODS: Between April and September 2007, 16 high-risk patients
      (13 females, aged 81 [76 - 88]) were operated on via a median sternotomy, using
      CPB and cardioplegia (Euro Score 17 [8 - 73]). All patients had significant
      aortic valve disease and seven of these patients had concomitant coronary artery
      disease. This pilot project was initiated with prior approval of the
      Institutional Review Board. All patients gave informed consent. RESULTS: One
      patient died during hospital stay for unknown reasons. Autopsy revealed no valve
      related pathologies. CPB time was 60 min (41 - 130), cross-clamping time was 36
      (22 - 79) min. Intraoperative as well as postoperative echocardiography revealed
      neither aortic insufficiency nor paravalvular leakage in any of the patients.
      CONCLUSIONS: The new approach as described here is a technically simple
      alternative to conventional aortic valve replacement in high-risk patients and
      offers the potential of less invasive approaches. It appears especially useful in
      patients with severe calcification of the aortic root. CPB and cross-clamping
      times were markedly reduced compared with patients who underwent conventional
      operations.

PMID- 18810697
TI  - Function of Contegra valved grafts after unifocalization.
AB  - BACKGROUND: Can Contegra grafts withstand high pressure? METHODS: The function of
      Contegra grafts implanted after unifocalization of major aortopulmonary
      collateral arteries (MAPCAs) in 10 patients was evaluated. Median age at repair
      was 194 days and two conduit sizes were used: 12 mm (n = 8) and 14 mm (n = 2).
      Echocardiography and heart catheterization findings were reviewed. RESULTS: Two
      patients died: one early after repair, one late. Death was not graft related. The
      median duration of observation for survivors was 31 (range 4 - 42) months. The
      postoperative right ventricular/left ventricular pressure ratio was greater than
      75 % in 9 patients. High pressures persisted in 6 survivors. Seven patients
      underwent interventional dilatation/stenting of pulmonary arteries on 19
      occasions. No obstruction was detected in the conduit. Graft valve regurgitation
      increased in 5 patients, but never exceeded grade 2 (n = 4). Freedom from
      reoperation for conduit dysfunction/failure was 100 % at month 42. CONCLUSION: At
      mid-term follow-up, the Contegra grafts withstood high pressure without
      significant dysfunction or aneurysmal dilatation requiring surgery. Contegra
      appears to be an acceptable alternative to the aortic homograft for use after
      unifocalization of MAPCAs in infancy.

PMID- 18810698
TI  - Can dantrolene protect spinal cord against ischemia/reperfusion injury? An
      experimental study.
AB  - BACKGROUND: The aim of this experimental study was to investigate the possible
      protective effect of dantrolene on neuronal injury induced by aortic
      ischemia/reperfusion (I/R). METHODS: Nineteen rabbits were divided into three
      groups: sham (group 1, n = 5, no I/R), control (group 2, n = 7, only I/R) and
      dantrolene (group 3, n = 7, dantrolene + I/R). Abdominal aortic occlusion between
      the renal arteries and iliac bifurcations was carried out for 30 min. The spinal
      cord functions of the subjects were assessed using the Tarlov Scale. Blood and
      cord tissue samples were taken for biochemical and histopathological evaluation.
      RESULTS: Tarlov scores in group 3 were significantly higher than in group 2 ( P <
      0.05). In group 3, the MDA levels of the spinal cord decreased significantly
      compared to those of group 2 ( P < 0.05). In rabbits with I/R (group 2), the GSH
      levels of the spinal cord decreased significantly compared to those of group 1 (
      P < 0.01), but dantrolene pretreatment significantly prevented a decrease in GSH
      levels. Histopathological examination showed that group 3 had less vascular
      proliferation, hemorrhage, edema and neuron loss than group 2. CONCLUSIONS: It
      was concluded that dantrolene applied after ischemia might help protect the
      spinal cord against ischemia/reperfusion injury.

PMID- 18810699
TI  - Outcome of off-pump coronary artery bypass in renal dialysis patients.
AB  - BACKGROUND: Renal dialysis patients are a subgroup at major operative risk when
      undergoing coronary artery bypass grafting (CABG). Even though CABG without
      cardiopulmonary bypass (CPB) has decreased the surgical risk and provided good
      short-term results, the long-term survival seems uncertain. We report here on the
      long-term outcome of CABG without CPB in renal dialysis patients. METHODS: From
      1998 to 2002, 44 renal dialysis patients underwent elective CABG without CPB,
      including 17 minimally invasive direct coronary artery bypass (MIDCAB) and 27 off
      pump CABG (OPCAB) procedures. There were 5 one-vessel, 12 two-vessel and 27 multi
      vessel coronary artery disease patients, who mainly had left internal thoracic
      artery (LITA) to left anterior descending coronary artery (LAD) grafting with an
      additional saphenous vein graft to non-LAD coronaries. RESULTS: All 44 patients
      were followed up for 44.4 +/- 31.2 months. Three (6.8 %) surgical deaths within
      30 days occurred and 25 late mortalities happened over a period of 2 - 79 months.
      The 5-year cumulative rate of total survival is 38.2 % and the freedom from
      cardiac death is 70.9 %. Using hazard analysis, old age (> 60 years) and
      incomplete coronary revascularization was found to significantly affect the total
      survival. CONCLUSIONS: CABG without CPB provided an acceptable surgical mortality
      and morbidity. The high incidence of non-cardiac death associated with dialysis
      complications had an adverse impact on the overall outcome. The LITA bypass
      operation method combined with intensive care for dialysis complications would
      hopefully fulfill the goal to improve the short- and long-term results in this
      subgroup.

PMID- 18810700
TI  - Thoracoscopic resection of a solitary pulmonary nodule in patients with a known
      history of malignancy.
AB  - BACKGROUND: Solitary pulmonary nodules found during the follow-up of cancer
      patients are generally considered to be lung metastases. However, a definite
      diagnosis should be established. METHODS: Between 1995 and 2005, all patients
      with a solitary lung nodule considered removable by a thoracoscopic approach and
      with a history of malignancy were included in this study. Lung wedge resection
      was performed to establish the morphological diagnosis. During follow-up further
      metastases and local recurrences were registered. Survival data were obtained in
      February 2007. RESULTS: Among our 34 patients (17 male and 17 female with a
      median age of 67.5 years), the most common primary cancers were colorectal (n =
      12) and kidney (n = 6). Two patients had a history of 2 cancers. Twenty-two
      patients (65 %) had lung metastases and 12 (35 %) had benign nodules. During
      follow-up (median 2.4 years) 7 patients (21 %) developed further lung metastases.
      Overall postoperative five-year survival was 50 % (95 % CI: 35 - 73 %).
      CONCLUSION: Not all solitary lung nodules in patients with previous malignancy
      are metastases. According to our survival results the thoracoscopic removal of a
      single lung metastasis was curative in many patients.

PMID- 18810701
TI  - Serum carcinoembryonic antigen level and pleural lavage cytology in woman with
      non-small cell lung cancer.
AB  - BACKGROUND: The prognostic impact of serum carcinoembryonic antigen (CEA) levels
      and pleural lavage cytology (PLC) in female patients with non-small cell lung
      cancer (NSCLC) were examined. METHODS: A consecutive series of 122 women with
      NSCLC who underwent surgical resection and PLC were included in the study.
      RESULTS: The 5-year survival rate of patients with preoperative serum normal and
      elevated CEA levels was 86.79 % and 58.46 %, respectively ( P = 0.0032). Positive
      PLC was present in 9/122 (7.38 %) of patients. The 5-year survival rate of
      patients with positive PLC findings was 33.33 %, which was significantly poor
      compared with that of patients with negative findings (83.16 %, P = 0.0010).
      Multivariate analysis indicated that pN status, preoperative serum CEA levels and
      PLC findings were independent prognostic factors. CONCLUSIONS: Preoperative serum
      CEA level and PLC findings were independent prognostic factors for female
      patients with NSCLC.

PMID- 18810702
TI  - Intramural hematoma of a cryopreserved aortic homograft.
AB  - Cryopreserved homografts are used in cases with prosthetic valve endocarditis
      since they present a higher resistance to infections than synthetic prostheses.
      Degeneration or endocarditis of the allograft aortic valve (AAV) has been
      described, but little data is available on allograft ascending aorta (AAA)
      disease. We describe the intraoperative finding and treatment of an extensive
      intramural hematoma of a cryopreserved homograft already affected by severe post
      infective aortic regurgitation. Since this is a very rare occurrence, there is no
      general consensus on how best to handle this combined disease. The replacement of
      AAV and supra-coronary AAA with biological products may be performed with low
      risks in patient with a complex pathology of the cryopreserved allograft.

PMID- 18810703
TI  - Beating heart valve surgery using stentless xenografts as a surgical alternative
      for patients with end-stage renal failure.
AB  - Patients suffering from end-stage renal disease are an inhomogeneous high-risk
      group with a substantial perioperative mortality and morbidity when undergoing
      cardiac surgical procedures[1-3]. Myocardial ischemia, reperfusion injury and
      myocardial edema are a few of the deleterious consequences of the traditional use
      of cardioplegic arrest when performing valve surgery,irrespective of the type of
      cardioplegia used [4-7]. Novel operative techniques are required to reduce these
      induced perioperative risks. Clinical studies in the past have demonstrated the
      efficacy of beating heart valve surgery in the high-risk patient using
      retrograde, antegrade or combined coronary perfusion with warm oxygenated blood
      [8, 9]. We chose to combine the superior hemodynamic profile of stentless
      xenografts with the concept of performing valve replacement on the empty beating
      heart with continuous antegrade application of oxygenated blood in 2 chronic
      hemodialysis patients.

PMID- 18810704
TI  - Tetralogy of fallot and absence of left pulmonary artery.
AB  - Unilateral absence of the pulmonary artery is a rare congenital lesion usually
      caused by backward displacement of the conical artery of the truncus arteriosus.
      The purpose of this report is to describe and discuss the treatment of an 8-year
      old patient who presented with cyanosis and was diagnosed with tetralogy of
      Fallot together with an absence of the left pulmonary artery and major
      aortopulmonary collateral arteries.

PMID- 18810705
TI  - Anomalous origin of left pulmonary artery branch from the aorta with Fallot's
      tetralogy.
AB  - We report the case of a ten-year-old boy who had often presented with respiratory
      distress since birth. Chest X-ray showed an enlarged right ventricle.
      Echocardiography demonstrated TGE characteristic features of Fallot's tetralogy
      and the left pulmonary artery could not be visualized. However, cardiac
      catheterization disclosed that the left pulmonary artery had an anomalous origin
      from the ascending aorta. The patient underwent total surgical correction of the
      defects. Nine days later, he was discharged.We present the results of a
      literature review of the incidence,physiopathological, clinical, diagnostic, and
      surgical characteristics of this rare disease.

PMID- 18810706
TI  - Bronchogenic cyst invading right atrium in a 5-year-old.
AB  - Primary bronchogenic cysts of cardiac origin or extension are rare. We report
      here on a 5-year-old girl with a bronchogenic cyst with a diameter of 5.0 x 4.5 x
      4.5 cm extending to the right atrial wall. Tumor enucleation and resection of the
      cyst together with the invaded right atrial wall was performed through a right
      posterolateral thoracotomy and an opening in the lateral pericardium. Resection
      of intrapericardial bronchogenic cysts is possible, although extensive invasion
      of cardiac structures may necessitate the use of cardiopulmonary bypass through a
      sternotomy.

PMID- 18810707
TI  - Congenital aberrant vessel as a source of massive hemothorax in blunt trauma.
AB  - A congenital aberrant vessel in the pleural cavity has rarely been described in
      the literature. It has been known to be a source of bleeding in spontaneous
      hemopneumothorax. As a result of the lack of pleural adhesions around the vessel,
      a congenital aberrant vessel is prone to deceleration injury. This is a case of
      massive hemothorax caused by a ruptured aberrant congenital vessel in a blunt
      trauma victim who sustained a two meter fall.

PMID- 18810708
TI  - Liposarcoma of the pleural cavity.
AB  - We report a case of pleural liposarcoma in a 58-year-old male patient with a
      twenty-year history of smoking, who was admitted for chest pain and chronic
      cough. Pleural liposarcoma is a rare, highly malignant intrathoracic tumor
      arising from the soft tissue of the pleural cavity. Chest radiograph and CT scan
      revealed a homogeneous mass with subtotal opacification of the left hemithorax.
      Tumor diagnosis was based on histopathological examination of a transparietal
      biopsy and revealed a mixed type liposarcoma. Surgical resection was performed
      followed by adjuvant irradiation. No recurrence was diagnosed during the follow
      up period of ten months and the patient continues to do well at the time of
      writing this paper.

PMID- 18810709
TI  - Downregulation of melanocortin-4 receptor during refeeding and its modulation by
      adrenalectomy in rats.
AB  - Melanocortin system and corticotropin releasing hormone (CRH) are implicated in
      the control of feeding behavior. Besides its anorexigenic effect on food intake,
      CRH is one of the most important regulators of hypothalamic-pituitary-adrenal
      (HPA) axis activity. Therefore, there could be an interplay between HPA axis
      activity and melanocortin system. We investigated the expression of melanocortin
      4 receptor (MC4-R) mRNA in the hypothalamus of rats after 14 days of food
      restriction or after a fasting-refeeding regimen, in sham or adrenalectomized
      rats. Male Wistar rats were subjected to free access to food or food ingestion
      restricted for 2 h a day (8-10 AM) during 14 d, when plasma corticosterone, ACTH,
      insulin, leptin concentrations, and MC4-R mRNA expression were determined before
      and after refeeding. Another set of rats was fasted for 48 h, followed by
      refeeding during 2 or 4 h on the seventh day after adrenalectomy (ADX) or sham
      surgery. On the day of the experiment, rats were anesthetized and perfused and
      the brain processed for MC4-R mRNA by in situ hybridization. Long-term reduction
      of food intake, either secondary to food restriction or adrenalectomy, reduced
      body weight gain and also leptin and insulin plasma concentrations. Food
      ingestion reduced MC4-R expression in the paraventricular nucleus in naive rats
      subjected to food restriction and also in sham rats fasted for 48 h. However,
      after ADX, MC4-R expression was not changed by refeeding. In conclusion, the
      present data indicate that MC4-R expression is downregulated by food ingestion
      and this response could be modulated by glucocorticoid withdrawal.

PMID- 18810710
TI  - Ischemic preconditioning phosphorylates mitogen-activated kinases and heat shock
      protein 27 in the diabetic rat heart.
AB  - Diabetes mellitus blocks protection by ischemic preconditioning (IPC), but the
      mechanism is not known. We investigated the effect of ischemic preconditioning on
      mitogen-activated protein kinases (extracellular signal-regulated kinases 1 and
      2, c-Jun N-terminal kinases, p38 mitogen-activated kinase) and heat shock protein
      27 phosphorylation in diabetic and nondiabetic rat hearts in vivo. Two groups of
      anaesthetized nondiabetic and diabetic rats underwent a preconditioning protocol
      (3 cycles of 3 min coronary artery occlusion and 5 min of reperfusion). Two
      further groups served as untreated controls. Hearts were excised for protein
      measurements by Western blot. Four additional groups underwent 25 min of coronary
      occlusion followed by 2 h of reperfusion to induce myocardial infarction. In
      these animals, infarct size was measured. IPC reduced infarct size in the
      nondiabetic rats but not in the diabetic animals. In diabetic rats, IPC induced
      phosphorylation of the mitogen-activated protein kinases and of heat shock
      protein 27. We conclude that protection by IPC is blocked by diabetes mellitus in
      the rat heart in vivo without affecting phosphorylation of mitogen-activated
      protein kinases or heat shock protein 27. Therefore, the blockade mechanism of
      diabetes mellitus is downstream of mitogen-activated kinases and heat shock
      protein 27.

PMID- 18810711
TI  - Long-term dietary lipid regimen alters adrenocortical function at the cellular
      level.
AB  - Evidence indicates that dietary lipids influence adrenocortical function. In the
      present study, weanling rats were fed isocaloric synthetic diets for 6 and 12
      months that contained 10% of one of the selected fatty acids as the predominant
      lipid: butter fat (high saturated, low polyunsaturated fat); olive oil
      (monounsaturated); corn oil (polyunsaturated); omega-3 ethyl ester mixture (long
      chain polyunsaturates); elevated eicosapentaenoic acid; elevated docosahexaenoic
      acid. Adrenocortical cells derived from individual rats were evaluated for
      corticosterone and aldosterone responses to adrenocorticotropic hormone (ACTH).
      All comparisons were to the butter fat diet. Adrenocortical cell sensitivity to
      ACTH was not affected by the diets. However, there were differences in basal and
      maximal ACTH-induced corticosteroid production. Compared to the butter fat diet,
      the other diets variably decreased cellular corticosteroid production.
      Corticosterone and aldosterone production were affected similarly. The greatest
      decrease was most often seen with the omega-3 mixture diet (about -67%). At 6
      months, the docosahexaenoic acid-elevated diet had selective suppressive actions
      on adrenocortical function whereas at 12 months, both docosahexaenoic and
      eicosahexaenoic acid-elevated diets had similar suppressive efficacies. The data
      indicate that a diet rich in high saturated, low polyunsaturated fat augments
      adrenocortical function and increasing the representation of long-chain
      unsaturated fatty acids suppresses adrenocortical function.

PMID- 18810713
TI  - Hyperglycemia as a risk factor in postinfarction patients.

PMID- 18810712
TI  - Metabolic and hormonal effects of oral DHEA in premenopausal women with HIV
      infection: a randomized, prospective, placebo-controlled pilot study.
AB  - Women with HIV infection use dehydroepiandrosterone (DHEA) because of its
      potential effects on mood and energy. We examined the effects of DHEA on the
      hypothalamic-pituitary-adrenal and gonadal axes and on insulin sensitivity.
      Fifteen HIV-positive women were randomized to receive placebo (6 subjects) or
      oral DHEA (9 subjects). ACTH-, CRF-, and GnRH-stimulation tests were performed
      before and after 8 weeks of treatment. DHEA, DHEA-S, dihydrotestosterone, total
      testosterone, free testosterone, sex hormone-binding globulin, estrone,
      estradiol, cortisol, insulin, IGF-1, IGFBP-1, IGFBP-3, and adiponectin in plasma
      or serum were measured. There was a significant increase in DHEA (p<0.004), DHEA
      S (p<0.008), total testosterone (p<0.008), dihydrotestosterone (p<0.004),
      androstenedione (p<0.04), and estrone (p<0.03) from baseline within the DHEA
      group but not within the placebo group. There was a significant increase in DHEA
      (p<0.0006), DHEA-S (p<0.032), total testosterone (p<0.01), and
      dihydrotestosterone (p<0.005) in the DHEA group compared with the placebo group.
      Oral DHEA produces significant increases in circulating DHEA, DHEA-S,
      testosterone, DHT, and, possibly, androstenedione and estrone levels in
      premenopausal women with HIV infection. In the current pilot study these hormone
      changes did not affect the pituitary or adrenal axis or insulin/IGF indices. Long
      term studies with larger groups of patients are needed to confirm these data and
      to determine their clinical significance.

PMID- 18810714
TI  - Atrial conduction and atrial fibrillation: what can we learn from surface ECG?
AB  - Despite the advancements in pharmacological and non-pharmacological management of
      atrial fibrillation (AF) observed during last decades, available treatment
      modalities and predictors of their success are still far from optimal.
      Understanding of pathophysiological mechanisms underlying AF and assessment of
      atrial electrophysiological properties using easily available non-invasive
      diagnostic tools such as surface ECG are essential for further improvement of
      patient-tailored treatment strategies. P-wave duration is generally accepted as
      the most reliable non-invasive marker of atrial conduction and its prolongation
      has been associated with history of AF. However, patients with paroxysmal AF
      without structural heart disease may not have any impressive P-wave prolongation
      thus suggesting that the global conduction slowing is not an obligatory
      requirement for development of AF. In these settings, the morphology of P-wave
      becomes an important source of information concerning propagation of atrial
      activation. One of the most common morphologies, i.e. biphasic configuration of P
      waves in right precordial leads has been considered a marker of left atrial
      enlargement but, seen in patients with structurally normal hearts, appears to be
      linked to an interatrial conduction defect. Recent advances in endocardial
      mapping technologies have linked certain P-wave morphologies with interatrial
      conduction patterns that may have clinical implications for invasive treatment of
      AF patients. The value of P-wave morphology extends beyond cardiac arrhythmias
      associated with atrial conduction delay and can be used for prediction of
      clinical outcome of wide range of cardiovascular disorders such as survival after
      myocardial infarction or the risk of stroke.

PMID- 18810715
TI  - The enigmatic sixth wave of the electrocardiogram: the U wave.
AB  - The U wave is the last, inconstant, smallest, rounded and upward deflection of
      the electrocardiogram. Controversial in origin, it is sometimes seen following
      the T wave with the TU junction along the baseline or fused with it and before P
      of the following cycle on the TP segment. In this review we will study its
      temporal location related to monophasic action potential, cardiac cycle and heart
      sounds, polarity, voltage or amplitude, frequency and shapecontour. We will
      analyze the clinical significance of negative, alternant, prominent U wave, and
      the difference between T wave with two peaks (T1-T2) and true U wave. Finally we
      will analyze the four main hypotheses about the source of U wave: repolarization
      of the intraventricular conducting system or Purkinje fibers system, delayed
      repolarization of the papillary muscles, afterpotentials caused by
      mechanoelectrical hypothesis or mechanoelectrical feedback, and the prolonged
      repolarization in the cells of the mid-myocardium ("M-cells").

PMID- 18810716
TI  - Effect of blood glucose levels on prognosis in acute myocardial infarction in
      patients with and without diabetes, undergoing percutaneous coronary
      intervention.
AB  - BACKGROUND: Diabetes mellitus (DM) is a significant factor regarding poor outcome
      in patients with myocardial infarction. Recently a new prognostic factor is under
      consideration - a baseline glucose level on admission. We sought to assess the
      influence of blood glucose levels on admission on prognosis of patients with
      acute ST-segment elevation myocardial infarction (STEMI) treated with
      percutaneous coronary intervention (PCI). METHODS AND RESULTS: Consecutive
      patients treated with PCI for STEMI were analyzed. Presence or absence of DM was
      the first grouping criterion. The secondary criterion was the blood glucose level
      on admission [threshold >or= 7.8 mmol/L (140 mg/dL)]. Hyperglycemic and non
      hyperglycemic subgroups were selected within both DM and non-DM groups according
      to the threshold. One-year mortality of diabetics was 16.0%. There was no
      significant difference in 1-year mortality between hyperglycemic and non
      hyperglycemic patients with DM. One-year mortality in the non-DM group was 5.6%.
      Patients without DM but with hyperglycemia showed a higher 1-year mortality rate
      than non-hyperglycemic patients (8.51% vs. 3.68%, p = 0.001). Multivariate
      analysis revealed that in the non-DM group blood glucose level (per 1 mmol/L) on
      admission was a factor affecting 1-year mortality [HR = 1.09 (1.01-1.17)].
      CONCLUSIONS: Elevated blood glucose levels in STEMI affect the prognosis of
      patients without DM; however, it is not an independent death risk factor of
      patients with DM treated with PCI.

PMID- 18810717
TI  - C-reactive protein and coronary calcium score association in coronary artery
      disease.
AB  - BACKGROUND: Both high-sensitivity C-reactive protein (hs-CRP) and spiral computed
      tomography coronary artery calcium score (CCS) are valid markers of
      cardiovascular risk. It is unknown whether hs-CRP is a marker of atherosclerotic
      burden or whether it reflects a process leading to acute coronary events. METHODS
      AND RESULTS: We studied the relation between hs-CRP and CCS in 143 patients that
      were candidates for coronary artery bypass grafting (CABG). In our cross
      sectional study, we found no significant association between hs-CRP and CCS in
      bivariate (p = 0.162) and multivariate (p = 0.062) analysis, but in patients who
      did not use statins this association was positive and significant in bivariate
      analysis (p = 0.001), and in multivariate analysis this association was negative
      and significant (p = 0.008). CONCLUSIONS: High-sensitivity CRP was not correlated
      with CCS. The relation between CRP and clinical events might not be related to
      atherosclerotic burden. Measures of inflammation, such as hs-CRP, and indices of
      atherosclerosis, such as CCS, are likely to provide distinct information
      regarding cardiovascular risk.

PMID- 18810718
TI  - Timing of life-threatening arrhythmias detected by implantable cardioverter
      defibrillators in relation to changes in cosmophysical factors.
AB  - BACKGROUND: Studies have linked the natural history of many pathologies with
      environmental physical activity. This study investigated the relationship between
      the occurrence of ventricular tachycardia/fibrillation (VT/VF) recorded by
      implantable cardioverter defibrillators (ICD) and geomagnetic and cosmic ray
      (neutron) activity. METHODS: The study group included 85 patients (73 men) with
      cardiomyopathy (80% ischemic) who underwent ICD placement in the years 1995-2006;
      74% had a left ventricular ejection fraction of < 30%. Data on the days on which
      VT/VF occurred (total number of days: 284) and the days on which the patients
      were treated (total number of treatments: 580) were collected from the ICD
      records. The findings were analyzed against levels of geomagnetic activity (GMA)
      (I degree -IV degree) and cosmic ray activity (CRA), derived from international
      observatories, on the same days and throughout the study period. RESULTS: On days
      of VT/VF, daily values of GMA level averaged 1.5 +/- 0.7, consistent with level I
      degree (quiet). The ratios of daily VT/VF episodes and treatment to GMA level for
      the whole study period were as follows: 1.2 level I; 0.9 level II; 0.69 level
      III; 0.78 level IV (r = -0.974; p = 0.02). Mean CRA on days of VT/VF was 9246.8
      +/- 299.0 imp/min, and for all 4383 days studied, 8805.33 +/- 411.4 imp/min (p <
      0.0001). CONCLUSIONS: In patients with predominantly ischemic cardiomyopathy and
      severe left ventricular dysfunction, VT/VF occurs more often on days of low GMA
      and high CRA. Further studies are needed to determine the underlying mechanism of
      the effect of neutron activity on cardiac electrical instability.

PMID- 18810719
TI  - Heart rate turbulence in patients with obstructive sleep apnea syndrome.
AB  - BACKGROUND: Heart rate turbulence (HRT) assessment is used as noninvasive method
      based on physiological sinus node response to the premature ventricular beat.
      Blunted HRT may indicate the autonomic nervous system impairment and can be
      helpful in identifying high-risk patients. Obstructive sleep apnea syndrome
      (OSAS) leads to cardiovascular complications. Autonomic nervous system and
      baroreflex dysfunctions may play the main role in the development of
      cardiovascular diseases. In the present study we aimed to assess HRT parameters
      in OSAS patients with and without coronary artery disease (CAD) in comparison to
      control group. METHODS: HRT analysis (TO--turbulence onset and TS--turbulence
      slope) was performed in 22 OSAS patients (confirmed by polisomnography, apnea
      hypopnea index >or= 15) and 21 healthy persons, obtained from 24-hour ECG
      recordings. CAD was confirmed in 10 OSAS patients, by positive exercise test ECG
      and coronary angiography. RESULTS: TS was significantly lower in OSAS patients in
      comparison to control group (1.14 +/- +/- 2.83 vs. 21.28 +/- 16.2, p < 0.001). TO
      didn't differ in both group. Significant negative correlation between TS and
      apnea-hypopnea index was observed (r = 0.49, p < 0.01). There were no significant
      HRT changes in OSAS and CAD patients vs. OSAS without CAD patients, although
      tendency to more impaired HRT in OSAS and CAD patients was observed. CONCLUSIONS:
      In OSAS patients, blunted HRT (especially TS) was observed. This may indicate
      baro-reflex dysfunction correlated with the severity of sleep disorders. The
      additional diagnosis of CAD did not significantly influence HRT parameters.

PMID- 18810720
TI  - Can prodromal symptoms predict recurrence of vasovagal syncope?
AB  - BACKGROUND: Vasovagal syncope (VVS) is a common symptom with empirical therapy
      and high recurrence rate. Our goal was to determine whether the pattern of
      presyncopal prodromal symptoms can predict the recurrence probability of
      vasovagal syncope. METHODS: Seventy-nine consecutive patients (male/female:
      53/26) with history of VVS and positive tilt table test (TTT) were enrolled in
      the study and completed the follow-up time for one year. They all had normal
      electrocardiograms and cardiac echocardiography without underlying disease. All
      of them were evaluated meticulously for prodromal symptoms (diaphoresis, nausea,
      palpitation and blurred vision) and frequency of syncopal spells in their past
      medical history. They received metoprolol at maximum tolerated dose and were
      taught tilt training as an empirical therapy after TTT. RESULTS: Fifty-four
      patients (68.4%) reported at least one of the four main prodromal symptoms.
      Median syncopal +/- presyncopal spells were 4 episodes. Forty-two patients
      (53.2%) experienced recurrence of syncope or presyncope during the follow-up
      period. In recurrent symptomatic patients, diaphoresis had been more
      significantly reported in their past medical history (p = 0.018) and they had
      more syncopal spells before TTT (p = 0.001). Age, gender and type of TTT response
      did not have any effect on the recurrence of VVS. CONCLUSIONS: Patients with a
      history of diaphoresis as a prodromal symptom and more pretilt syncopal attacks
      experience more syncopal or presyncopal spells during follow-up.

PMID- 18810721
TI  - In-hospital management and mortality in elderly patients with non-ST-segment
      elevation acute coronary syndromes treated in centers without on-site invasive
      facilities.
AB  - BACKGROUND: The purpose was to assess age-related differences in hospital
      management and mortality in non-ST-elevation acute coronary syndrome (NSTE ACS)
      patients treated conservatively, with a focus on the influence of aggressive
      pharmacological treatment on in-hospital clinical outcome. METHODS: We identified
      807 NSTE ACS patients treated conservatively in the 29 hospitals participating in
      the Krakow Registry of Acute Coronary Syndromes from February to March 2005 and
      from December 2005 to January 2006. Out of 807 patients' 32.1% were less than 65
      years of age, 33% from 65 to 74, 30.5% from 75 to 84, and 5.3% >or= 85. For all
      patients, pharmacotherapy index based on the use of pharmacological treatment
      regimen during hospital stay was assessed. Each patient received 1 point for each
      of the following guideline-recommended drugs used: aspirin, clopidogrel,
      glycoprotein IIb/IIIa inhibitor, LMWH, beta-blocker, ACE inhibitor/angiotensin II
      receptor blocker and statin - the range of points being from 0 to 7. RESULTS:
      Significant age-related differences in baseline characteristics and
      pharmacotherapy index values were found. In-hospital mortality was higher in
      elderly patients (2.4% vs. 3.4% vs. 8.9% vs. 14.0%, respectively for age groups,
      p < 0.0001). Similarly, in non-shock patients and in patients with elevated
      cardiac markers, age-dependent differences in mortality were observed.
      Independent predictors of in-hospital death were: age, cardiogenic shock,
      elevated cardiac markers and pharmacotherapy index. CONCLUSIONS: Advanced age is
      associated with less aggressive pharmacological treatment and higher in-hospital
      mortality in NSTE ACS patients remaining in community hospitals for conservative
      treatment. Broader implementation of current guidelines and more frequent
      invasive treatment might improve the outcomes of NSTE ACS patients regardless of
      age.

PMID- 18810722
TI  - Restenosis is not associated with stent length in a pig model of coronary stent
      implantation.
AB  - BACKGROUND: The aim of this study was to determine if stent length is by itself a
      risk factor for intimal proliferation and restenosis. Long lesions represent an
      independent risk factor for restenosis after coronary stent implantation. A
      longer stented segment might result in a higher probability of restenosis.
      METHODS: Twenty-two 7-month-old male farm pigs underwent implantation of two
      steel stents, one short (8 mm length) and one long (16 mm length), in the right
      coronary artery. The pigs were sacrificed 28 days after stent implantation and
      histomorphometric analysis of the coronary arteries was performed for neointimal
      area proliferation and area stenosis evaluation. RESULTS: Seventeen short stents
      and 19 long stents were finally implanted. There were no differences in
      neointimal proliferation (1.84 +/- 0.64 mm2 vs. 1.81 +/- 0.94 mm2, p = 0.84),
      area stenosis (40 +/- 9% vs. 41 +/- 19%, p = 0.86) and lumen area (2.96 +/- 1.30
      mm2 vs. 2.51 +/- +/- 1.18 mm2, p = 0.21) between the short stent group and the
      long stent group, respectively. CONCLUSIONS: These data suggest that stent length
      by itself does not influence restenosis extent in the porcine model.

PMID- 18810723
TI  - Recurrent myocardial infarction in a young football player with antithrombin III
      deficiency.
AB  - Acute myocardial infarction is a rare condition in young athletes. One of the
      causes could be a hypercoagulable state due to congenital antithrombin III
      deficiency, together with a prothrombotic state soon after strenuous physical
      training. We present the case of myocardial reinfarction in young football player
      with antithrombin III deficiency, treated with primary percutaneous coronary
      intervention and drug eluting stent, as well as the functional repercussions of
      continuous intensive physical activity.

PMID- 18810724
TI  - Mitral valve thrombus, embolic events, carotid artery stenosis and patent foramen
      ovale.
AB  - Patent foramen ovale (PFO) is associated with high prevalence of stroke and
      systemic embolisation. A 53-year-old man had mitral valve thrombus and PFO
      diagnosed by echocardiography, in addition to carotid artery stenosis and embolic
      events including transient ischemia attack, retinal artery occlusion and left
      kidney infarct. Surgical removal of the mitral valve thrombus and concomitant
      coronary artery bypass were performed under cardiopulmonary bypass. We believe
      this is the sole reported case of mitral valve thrombus associated with a PFO.
      Due to their embolic potential, concomitant PFOs should be closed during heart
      operations, and independent ones deserve interventional management in high-risk
      patients.

PMID- 18810725
TI  - Diffuse large B cell lymphoma presenting as a cardiac mass and odynophagia.
AB  - Cardiac involvement as an initial presentation of malignant lymphoma is a rare
      occurrence. We describe the case of a 77-year-old man who had initially been
      diagnosed with a left atrial mass on an echocardiogram, presenting with
      progressive dyspnea, dysphagia, odynophagia and fevers. The cardiac mass had been
      managed as an outpatient with full anticoagulation for the suspicion of clot. On
      admission, cardiac magnetic resonance imaging revealed a large mediastinal mass
      invading the left atrium that originated from the oesophagus. A barium
      oesophagram revealed an apple core lesion involving the distal third of the
      oesophagus. A subsequent computed tomography scan demonstrated a large
      mediastinal soft tissue mass and paratracheal lymphadenopathy. A flexible upper
      endoscopy revealed an oesophageal mass that was approximately 10 cm in length,
      irregular at the margins, and with a very necrotic appearance. This was biopsied,
      revealing findings consistent with high grade diffuse large B cell lymphoma. This
      case illustrates lymphoma presenting with dyspnea, odynophagia and a left atrial
      mass. To our knowledge, there are no reported cases of diffuse large B cell
      lymphoma presenting as odynophagia and a cardiac mass.

PMID- 18810726
TI  - Mitral kissing vegetation.

PMID- 18810727
TI  - Comfortable textile-based electrocardiogram systems for very long-term
      monitoring.

PMID- 18810728
TI  - Cardiac rehabilitation following myocardial infarction.
AB  - This article provides an overview of current recommendations regarding cardiac
      rehabilitation (CR) after myocardial infarction and its clinical application.
      Evidence shows that exercise- based CR after cardiac events positively affects
      the extent of disability and level of quality of life, and has also important
      beneficial role in modifying morbidity and mortality. Cardiac rehabilitation is
      an integral component of the care for patients who have undergone acute
      myocardial infarction, after invasive coronary procedures and those with chronic
      stable angina. Although in the last four decades physical training has assumed a
      major role in health care of coronary artery disease patients, cardiac
      rehabilitation does not consist exclusively of regular exercising. Comprehensive
      cardiac rehabilitation should include the following components: clinical
      evaluation, optimization of pharmacotherapy, physical training, psychological
      rehabilitation, evaluation and reduction of coronary disease risk factors, life
      style modification, and patient education. Comprehensive cardiac rehabilitation
      should be addressed by the designated team (physician, physiotherapist, nurse,
      psychologist, dietician, social worker) immediately after acute phase of
      myocardial infarction and should contain individualized programs designed to
      optimize physical, psychological, social and emotional status. Modern model of
      comprehensive cardiac rehabilitation should be initiated as early as possible,
      continued for required time, properly staged, and individualized depending on
      clinical status of the patients.

PMID- 18810729
TI  - The mechanisms of ventricular tachycardia, Leo Schamroth and Guy Fontaine 30
      years ago.

PMID- 18810730
TI  - Gold- and silver-catalyzed tandem amination/ring expansion of cyclopropyl
      methanols with sulfonamides as an expedient route to pyrrolidines.
AB  - An efficient synthetic route to pyrrolidines that relies on AuCl/AgOTf-catalyzed
      tandem amination/ring expansion of substituted cyclopropyl methanols with
      sulfonamides is reported herein. The reactions proceed rapidly at 100 degrees C
      with catalyst loadings as low as 2 mol % and produce the pyrrolidine products in
      yields of 30-95 %. The method was shown to be applicable to a broad range of
      cyclopropyl methanols, including unactivated ones, and sulfonamide substrates
      containing electron-withdrawing, electron-donating, and sterically-demanding
      substituents. The mechanism is suggested to involve activation of the alcohol
      substrate by the AuCl/AgOTf catalyst, followed by ionization of the starting
      material, which causes ring opening of the cyclopropane moiety and trapping by
      the sulfonamide nucleophile. The resultant aminated acyclic intermediate
      undergoes subsequent intramolecular hydroamination to give the pyrrolidine.

PMID- 18810731
TI  - A new class of hydroxo-bridged heptacopper(II) clusters with an acentrosymmetric
      corner-sharing double-cubane framework supported by D-penicillaminedisulfides.

PMID- 18810732
TI  - Beta-cyclodextrin-appended giant amphiphile: aggregation to vesicle polymersomes
      and immobilisation of enzymes.
AB  - A giant amphiphile consisting of polystyrene end-capped with permethylated beta
      cyclodextrin was synthesised and found to form vesicular structures when injected
      as a solution in THF into water. The ability of the cyclodextrins on the surface
      of the polymersomes to form inclusion complexes with hydrophobic compounds was
      tested by carrying out a competition experiment with a fluorescent probe
      sensitive to the polarity of the surrounding medium. It was found that 1
      adamantol can displace the fluorescent probe from the cavities of the
      cyclodextrin moieties of the polymersomes. The recognition of molecules by cell
      membranes in nature is often based on interactions with specific membrane
      receptors. To mimic this behaviour, the enzyme horseradish peroxidase was
      modified with adamantane groups through a poly(ethylene glycol) spacer and its
      interaction with the polymersomes was investigated. It was established that the
      presence of adamantane moieties on each enzyme allowed a host-guest interaction
      with the multifunctional surface of the polymersomes.

PMID- 18810733
TI  - Cobalt-catalyzed regioselective synthesis of indenamine from o-iodobenzaldimine
      and alkyne: intriguing difference to the nickel-catalyzed reaction.

PMID- 18810734
TI  - New synthetic approach for the construction of multisubstituted 2-acyl furans by
      the IBX-mediated cascade oxidation/cyclization of cis-2-En-4-yn-1-ols (IBX=2
      iodoxybenzoic acid).

PMID- 18810736
TI  - Enantioseparation of nuarimol by affinity electrokinetic chromatography-partial
      filling technique using human serum albumin as chiral selector.
AB  - The present paper deals with the enantiomeric separation of nuarimol enantiomers
      by affinity EKC-partial filling technique using HSA as chiral selector. Firstly,
      a study of nuarimol interactions with HSA by CE-frontal analysis was performed.
      The binding parameters obtained for the first site of interaction were n(1) =
      0.84; K(1) = 9.7 +/- 0.3x10(3 )M(-1) and the protein binding percentage of
      nuarimol at physiological concentration of HSA was 75.2 +/- 0.2%. Due to the
      moderate affinity of nuarimol towards HSA the possibility of using this protein
      as chiral selector for the separation of nuarimol using the partial filling
      technique was evaluated. A multivariate optimization approach of the most
      critical experimental variables in enantioresolution, running pH, HSA
      concentration and plug length was carried out. Separation of nuarimol enantiomers
      was obtained under the following selected conditions: electrophoretic buffer
      composed of 50 mM Tris at pH 7.3; 160 muM HSA solution applied at 50 mbar for 156
      s as chiral selector; nuarimol solutions in the range of 2-8x10(-4) M injected
      hydrodynamically at 30 mbar for 2 s and the electrophoretic runs performed at 30
      degrees C applying 15 kV voltage. Resolution, accuracy, reproducibility speed and
      cost of the proposed method make it suitable for quality control of the
      enantiomeric composition of nuarimol in formulations and for further
      toxicological studies. The results showed a different affinity between nuarimol
      enantiomers towards HSA.

PMID- 18810740
TI  - Photophysical and duplex-DNA-binding properties of distamycin dimers based on
      4,4'- and 2,2'-dialkoxyazobenzenes as the core.
AB  - Distamycin-based tetrapeptide (1) was covalently tethered to both ends of the
      central dihydroxyazobenzene moiety at either the 2,2' or 4,4' positions. This
      afforded two isomeric, distamycin-azobenzene-distamycin systems, 2 (para) and 3
      (ortho), both of them being photoisomerizable. Illumination of these conjugates
      in solution at approximately 360 nm induced photoisomerization and the time
      course of the process was followed by UV/Vis and (1)H NMR spectroscopy. The
      kinetics of the thermal reversion at various temperatures of cis to trans isomers
      of the conjugates obtained after photoillumination were also examined. This
      afforded the respective thermal-activation parameters. Both the molecular
      architecture and the location of the substituent around the core azobenzene
      determined the rate and activation-energy barrier for the cis-to-trans back
      isomerization of these conjugates in solution. Duplex-DNA binding of the
      conjugates and the changes in DNA-binding efficiency upon photoisomerization was
      also examined by CD spectroscopy, thermal denaturation studies, and a Hoechst
      displacement assay. The conjugate 2 showed higher DNA-binding affinity and a
      greater change in the DNA-binding efficiency upon photoisomerization compared
      with its 2,2'-disubstituted counterpart. The experimental findings were
      substantiated by using molecular-docking studies involving each conjugate with a
      model duplex d[(GC(AT)(10)CG)](2) DNA molecule.

PMID- 18810741
TI  - Relationship between carbon nanotube structure and electrochemical behavior:
      heterogeneous electron transfer at electrochemically activated carbon nanotubes.
AB  - The electrochemical activation of multiwalled carbon nanotubes (MWCNTs) (at
      potentials of 1.5-2.0 V vs Ag/AgCl for 60-360 s) results in significantly
      increased rate constants (k(0)((obs))) for heterogeneous electron-transfer with
      [Fe(CN)(6)](3-/4-) (from 8.34 x 10(-5) cm s(-1) for as-received MWCNTs to 3.67 x
      10(-3) cm s(-1) for MWCNTs that were electrochemically activated at 2.0 V for 180
      s). The increase in the value of k(0)((obs)) arises from the introduction of wall
      defects exposing edge planes of the MWCNTs, as observed by high-resolution TEM.
      The density of the edge plane defects increases from almost zero (for as-received
      MWCNTs) to 3.7 % (for MWCNTs electrochemically activated at 2.0 V for 180 s).
      High-resolution X-ray photoelectron spectroscopy (HR-XPS), Raman spectroscopy,
      and electrochemical impedance spectroscopy were used to gain a better
      understanding of the phenomena. HR-XPS revealed that the increase in
      electrochemical activation potential increases the number of oxygen-containing
      groups on the surface of carbon nanotubes.

PMID- 18810742
TI  - Self-assembled organic microtubes from amphiphilic molecules.
AB  - Getting the sizes sorted out: In recent years, there have been increasing numbers
      of reports about self-assembled nano- or microtubular structures because of their
      potential uses in a variety of technical applications, which are largely
      determined by the tube sizes. This Focus Review highlights microsized self
      assembled organic tubular structures formed in aqueous solutions and organic
      solvents. In recent years, there have been increasing numbers of reports about
      self-assembled nano- or microtubular structures, because they have potential uses
      in nanofabrication, purification, medical, and encapsulation applications. A wide
      range of tubular structures have been constructed by the self-assembly of
      amphiphilic molecules in aqueous solution or organic solvents. The diameters of
      self-assembled tubular structures range between 10 nm and 30 mum. One of the most
      important factors that determine their suitability for technical applications is
      the size of the tubes. Therefore, analyzing and sorting tubular structures
      according to their size is essential. This Focus Review highlights microsized
      self-assembled organic tubular structures formed in aqueous solutions and organic
      solvents.

PMID- 18810743
TI  - 1-, 2-, and 4-ethynylpyrenes in the structure of twisted intercalating nucleic
      acids: structure, thermal stability, and fluorescence relationship.
AB  - A postsynthetic, on-column Sonogashira reaction was applied on DNA molecules
      modified by 2- or 4-iodophenylmethylglycerol in the middle of the sequence, to
      give the corresponding ortho- and para-twisted intercalating nucleic acids (TINA)
      with 1-, 2-, and 4-ethynylpyrene residues. The convenient synthesis of 2- and 4
      ethynylpyrenes started from the hydrogenolysis of pyrene that has had the sulfur
      removed and separation of 4,5,9,10-tetrahydropyrene and 1,2,3,6,7,8
      hexahydropyrene, which were later converted to the final compounds by successive
      Friedel-Crafts acetylation, aromatization by 2,3-dichloro-5,6-dicyano-1,4
      benzoquinone, and a Vilsmeier-Haack-Arnold transformation followed by a Bodendorf
      fragmentation. Significant alterations in thermal stability of parallel triplexes
      and antiparallel duplexes were observed upon changing the attachment of
      ethynylpyrenes from para to ortho in homopyrimidine TINAs. Thus, for para-TINAs
      the bulge insertion of an intercalator led to high thermal stability of Hoogsteen
      type parallel triplexes and duplexes, whereas Watson-Crick-type duplexes were
      destabilized. In the case of ortho-TINA, both Hoogsteen and Watson-Crick-type
      complexes were stabilized. Alterations in the thermal stability were highly
      influenced by the ethynylpyrene isomers used. This also led to TINAs with
      different changes in fluorescence spectra depending on the secondary structures
      formed. Stokes shift of approximately 100 nm was detected for pyren-2
      ylethynylphenyl derivatives, whereas values for 1- and 4-ethynylpyrenylphenyl
      conjugates were 10 and 40 nm, respectively. In contrast with para-TINAs,
      insertion of two ortho-TINAs opposite each other in the duplex as a pseudo-pair
      resulted in formation of an excimer band at 505 nm for both 1- and 4
      ethynylpyrene analogues, which was also accompanied with higher thermal
      stability.

PMID- 18810744
TI  - Spontaneous resolution of chiral polyoxometalate-based compounds consisting of 3D
      chiral inorganic skeletons assembled from different helical units.
AB  - Four enantiomerically pure 3D chiral POM-based compounds,
      [Ni(2)(bbi)(2)(H(2)O)(4)V(4)O(12)]2 H(2)O (1 a and 1 b) and
      [Co(bbi)(H(2)O)V(2)O(6)] (2 a and 2 b) (bbi=1,1'-(1,4-butanediyl)bisimidazole)
      based on the achiral ligand, different vanadate chains, and different metal
      centers have been synthesized by hydrothermal methods. Single-crystal X-ray
      diffraction analyses revealed that 1 a and 1 b, and 2 a and 2 b, respectively,
      are enantiomers. In 1 a and 1 b two kinds of vanadate chains with different screw
      axes link Ni cations to generate 3D chiral inorganic skeletons, which are
      connected by the achiral bbi ligands to form complicated 3D 3,4-connected chiral
      self-penetrating frameworks with (7(2)8)(7(2)8(2)9(2))(7(3)8(2)10) topology. They
      represent the first examples of chiral self-penetrating frameworks known for
      polyoxometalate (POM) systems. Contrary to 1 a and 1 b, in 2 a and 2 b the
      vanadate chains link Co(II) cations to generate 3D chiral inorganic skeletons,
      which are assembled from two kinds of heterometallic helical units of opposite
      chirality along the c axes. The chiral inorganic skeletons are connected by bbi
      to form 3D 3,4-connected chiral POM-based frameworks with
      (6(2)8)(2)(6(2)8(2)10(2)) topology. It is believed that the asymmetrical
      coordination modes of the metal cations in 1 a-2 b generate the initial chiral
      centers, and that the formation of the various helical units and the hydrogen
      bond interactions are responsible for preservation of the chirality and
      spontaneous resolution when the chirality is extended into the homochiral 3D
      networks. This is the first known report of chiral POM-based compounds consisting
      of 3D chiral inorganic skeletons being obtained by spontaneous resolution upon
      crystallization in the absence of any chiral source, which may provide a rational
      strategy for synthesis of chiral POM-based compounds by using achiral ligands and
      POM helical units.

PMID- 18810745
TI  - Contributions from atomic p(Se), d(Se), and f(Se) orbitals to absolute
      paramagnetic shielding tensors in neutral and charged SeHn and some oxides
      including the effect of methyl and halogen substitutions on sigmap(Se).
AB  - Contributions from atomic p(Se), d(Se), and f(Se) orbitals to sigmap(Se) are
      evaluated for neutral and charged Se*Hn (*=null, +, or -) and some oxides to
      build the image of the contributions. The effect of methyl and halogen
      substitutions is also examined employing RrSe*XxOo (*=null, +, or -) where R=H or
      Me; X=F, Cl, or Br. The p(Se) contributions are larger than 96 % for SeH-
      (Cinfinityv), SeH2 (C2v), SeH3 + (C3v), SeH3 + (D3h), and SeH4 (Td). Therefore,
      sigmap(Se) of these compounds can be analyzed based on p(Se). The p(Se)
      contributions are 79-75 % for SeH4 (TBP), SeH5 + (TBP), SeH5 + (SP), and SeH5 -
      (SP). Methyl and halogen substitutions increase the contributions by 1-2 % (per
      Me) and 4-7 % (per X), respectively. The contributions are 92-79 % for H2SeO
      (Cs), H2SeO2 (C2v), and H4SeO (C2v). The values are similarly increased by the
      substitutions. Consequently, sigmap(Se) of these compounds can be analyzed based
      on p(Se) with some corrections by d(Se). The p(Se) contribution of SeH6 (Oh) is
      52 %: sigmap(Se: SeH6 (Oh)) must be analyzed based on both p(Se) and d(Se). The
      contributions for the Me and X derivatives of SeH(6) amount to 86-77 %.
      Therefore, sigmap(Se) of the derivatives can also be analyzed mainly based on
      p(Se) with some corrections by d(Se). Contributions from f(Se) are negligible.
      Contributions from 4p(Se) in vacant orbitals are also considered. A utility
      program derived from the Gaussian 03 (NMRANAL-NH03G) is applied to evaluate the
      contributions.

PMID- 18810746
TI  - Theoretical study on the factors controlling the stability of the borate
      complexes of ribose, arabinose, lyxose, and xylose.
AB  - Recent experimental studies suggest that complexation with borate minerals
      stabilizes ribose, and that the borate complex of ribose is more stable than
      those of related aldopentoses, that is, arabinose, lyxose, and xylose. These
      findings have revived the debate on the plausibility of the RNA-world theory,
      because they provide an explanation for the stabilization and selection of ribose
      in prebiotic conditions. In this paper we unravel the factors that make the
      ribose-borate complex the most stable one. For this purpose, we have investigated
      the structure and stability of the ribose-, arabinose-, lyxose-, and xylose
      borate complexes using density functional theory and a continuum solvent
      approach. The computed results reveal that in the aldopentose-borate complexes,
      the electrostatic field of the borate is strong enough to change the orientation
      of the nearby hydroxyl groups compared to noncomplexed aldopentoses. In addition,
      we show that the distinct stability of the ribose-borate 2:1 complex can be
      attributed to 1) a strong hydrogen bond between the ribose 3-OH and one of the
      negatively charged borate oxygen atoms, and 2) a favorable contact between the
      aqueous medium and the 5-CH(2)OH group due to the space separation between the 5
      CH(2)OH group and the borate anion.

PMID- 18810747
TI  - Effect of the nature of the metal atom on hydrogen bonding and proton transfer to
      [Cp*MH3(dppe)]: tungsten versus molybdenum.
AB  - The hydrogen-bonding and proton-transfer pathway to complex [Cp*W(dppe)H(3)]
      (Cp*=eta(5)-C(5)Me(5); dppe=Ph(2)PCH(2)CH(2)PPh(2)) was investigated
      experimentally by IR, NMR, UV/Vis spectroscopy in the presence of fluorinated
      alcohols, p-nitrophenol, and HBF(4), and by using DFT calculations for the
      [CpW(dhpe)H(3)] model (Cp=eta(5)-C(5)H(5); dhpe=H(2)PCH(2)CH(2)PH(2)) and for the
      real system. A study of the interaction with weak acids (CH(2)FCH(2)OH,
      CF(3)CH(2)OH, (CF(3))(2)CHOH) allowed the determination of the basicity factor,
      E(j)=1.73+/-0.01, making this compound the most basic hydride complex reported to
      date. A computational investigation revealed several minima for the
      [CpW(dhpe)H(3)] adducts with CF(3)CH(2)OH, (CF(3))(2)CHOH, and 2(CF(3))(2)CHOH
      and confirms that these interactions are stronger than those established by the
      Mo analogue. Their geometries and relative energies are closely related to those
      of the homologous Mo systems, with the most stable adducts corresponding to H
      bonding with M-H sites, however, the geometric and electronic parameters reveal
      that the metal center plays a greater role in the tungsten systems. Proton
      transfer equilibria are observed with the weaker proton donors, the proton
      transfer step for the system [Cp*W(dppe)H(3)]/HOCH(CF(3))(2) in toluene having
      DeltaH=(-3.9+/-0.3) kcal mol(-1) and DeltaS=(-17+/-2) cal mol(-1) K(-1). The
      thermodynamic stability of the proton-transfer product is greater for W than for
      Mo. Contrary to the Mo system, the protonation of the [Cp*W(dppe)H(3)] appears to
      involve a direct proton transfer to the metal center without a nonclassical
      intermediate, although assistance is provided by a hydride ligand in the
      transition state.

PMID- 18810748
TI  - Nacre calcification in the freshwater mussel Unio pictorum: carbonic anhydrase
      activity and purification of a 95 kDa calcium-binding glycoprotein.
AB  - The formation of the molluscan shell is finely tuned by macromolecules of the
      shell organic matrix. Previous results have shown that the acid-soluble fraction
      of the nacre matrix of the freshwater paleoheterodont bivalve Unio pictorum shell
      displays a number of remarkable properties, such as calcium-binding activity, the
      presence of extensive glycosylations and the capacity to interfere at low
      concentration with in vitro calcium carbonate precipitation. Here we have found
      that the nacre-soluble matrix exhibits a carbonic anhydrase activity, an
      important function in calcification processes. This matrix is composed of three
      main proteinaceous discrete fractions. The one with the highest apparent
      molecular weight is a 95 kDa glycoprotein that is specific to the nacreous layer.
      P95, as it is provisionally named, is enriched in Gly, Glx and Asx and exhibits
      an apparent pI value of approximately 4, or approximately 7 when chemically
      deglycosylated. Furthermore, its glycosyl moiety, consisting of sulfated
      polysaccharides, is involved in calcium binding. Purified fractions of the three
      main proteins were digested with trypsin, and the resulting peptides were
      analysed by mass spectrometry. Our results suggest that identical peptides are
      constitutive domains of the different proteins. Partial primary structures were
      obtained by de novo sequencing and compared with known sequences from other
      mollusc shell proteins. Our results are discussed from an evolutionary viewpoint.

PMID- 18810749
TI  - Biosynthesis of the vitamin E compound delta-tocotrienol in recombinant
      Escherichia coli cells.
AB  - The biosynthesis of natural products in a fast growing and easy to manipulate
      heterologous host system, such as Escherichia coli, is of increasing interest in
      biotechnology. This procedure allows the investigation of complex natural product
      biosynthesis and facilitates the engineering of pathways. Here we describe the
      cloning and the heterologous expression of tocochromanol (vitamin E) biosynthesis
      genes in E. coli. Tocochromanols are synthesized solely in photosynthetic
      organisms (cyanobacteria, algae, and higher green plants). For recombinant
      tocochromanol biosynthesis, the genes encoding hydroxyphenylpyruvate dioxygenase
      (hpd), geranylgeranylpyrophosphate synthase (crtE), geranylgeranylpyrophosphate
      reductase (ggh), homogentisate phytyltransferase (hpt), and tocopherol-cyclase
      (cyc) were cloned in a stepwise fashion and expressed in E. coli. Recombinant E.
      coli cells were cultivated and analyzed for tocochromanol compounds and their
      biosynthesis precursors. The expression of only hpd from Pseudomonas putida or
      crtE from Pantoea ananatis resulted in the accumulation of 336 mg L(-1)
      homogentisate and 84 microg L(-1) geranylgeranylpyrophosphate in E. coli
      cultures. Simultaneous expression of hpd, crtE, and hpt from Synechocystis sp.
      under the control of single tac-promoter resulted in the production of methyl-6
      geranylgeranyl-benzoquinol (67.9 microg g(-1)). Additional expression of the
      tocopherol cyclase gene vte1 from Arabidopsis thaliana resulted in the novel
      formation of a vitamin E compound-delta-tocotrienol (15 microg g(-1))-in E. coli.

PMID- 18810750
TI  - Stable beta turns of tripeptides in water through cation-pi interactions.

PMID- 18810756
TI  - Semiconductor quantum dots for bioanalysis.
AB  - Semiconductor nanoparticles, or quantum dots (QDs), have unique photophysical
      properties, such as size-controlled fluorescence, have high fluorescence quantum
      yields, and stability against photobleaching. These properties enable the use of
      QDs as optical labels for the multiplexed analysis of immunocomplexes or DNA
      hybridization processes. Semiconductor QDs are also used to probe biocatalytic
      transformations. The time-dependent replication or telomerization of nucleic
      acids, the oxidation of phenol derivatives by tyrosinase, or the hydrolytic
      cleavage of peptides by proteases are probed by using fluorescence resonance
      energy transfer or photoinduced electron transfer. The photoexcitation of QD
      biomolecule hybrids associated with electrodes enables the photoelectrochemical
      transduction of biorecognition events or biocatalytic transformations. Examples
      are the generation of photocurrents by duplex DNA assemblies bridging CdS NPs to
      electrodes, and by the formation of photocurrents as a result of biocatalyzed
      transformations. Semiconductor nanoparticles are also used as labels for the
      electrochemical detection of DNA or proteins: Semiconductor NPs functionalized
      with nucleic acids or proteins bind to biorecognition complexes, and the
      subsequent dissolution of the NPs allows the voltammetric detection of the
      related ions, and the tracing of the recognition events.

PMID- 18810758
TI  - The genomic profile of HER2-amplified breast cancers: the influence of ER status.
AB  - Expression profiling studies have suggested that HER2-amplified breast cancers
      constitute a heterogeneous group that may be subdivided according to their ER
      status: HER2-amplified ER-positive breast carcinomas that fall into the luminal B
      cluster; and HER2-amplified ER-negative cancers which form a distinct molecular
      subgroup, known as the erbB2 or HER2 subgroup. ER-negative breast cancer differs
      significantly from ER-positive disease in the pattern, type, and complexity of
      genetic aberrations. Here we have compared the genomic profiles of ER-positive
      and ER-negative HER2-amplified cancers using tiling path microarray-based
      comparative genomic hybridization (aCGH). Validation of the differentially
      amplified regions was performed in an independent series of 70 HER2-amplified
      breast cancers. Although HER2-amplified cancers had remarkably complex patterns
      of molecular genetic aberrations, ER-positive and ER-negative HER2-amplified
      breast carcinomas shared most molecular genetic features as defined by aCGH.
      Genome-wide Fisher's exact test analysis revealed that less than 1.5% of the
      genome was significantly differentially gained or lost in ER-positive versus ER
      negative HER2-amplified cancers. However, two regions of amplification were
      significantly associated with ER-positive carcinomas, one of which mapped to
      17q21.2 and encompassed GJC1, IGFBP4, TNS4, and TOP2A. Chromogenic in situ
      hybridization analysis of an independent validation series confirmed the
      association between ER status and TOP2A amplification. In conclusion, although
      hormone receptor status does not determine the overall genetic profile of HER2
      amplified breast cancers, specific genetic aberrations may be characteristic of
      subgroups of HER2 breast cancers.

PMID- 18810759
TI  - A critical role for TRAIL in resolution of granulomatous experimental autoimmune
      thyroiditis.
AB  - Granulomatous experimental autoimmune thyroiditis (G-EAT) is induced by mouse
      thyroglobulin (MTG)-sensitized splenocytes activated in vitro with MTG and IL-12.
      Thyroid lesions reach maximal severity 20 days after cell transfer, and usually
      resolve or progress to fibrosis by day 60 depending on the extent of thyroid
      damage at day 20. Our previous studies indicated that neutralization of TNF-alpha
      or FasL had no effect on G-EAT induction, but neutralization of TNF-alpha
      promoted, while neutralization of FasL inhibited, G-EAT resolution. TNF-related
      apoptosis-inducing ligand (TRAIL) is a member of the TNF superfamily. This study
      was undertaken to define the role of endogenous TRAIL in G-EAT development and/or
      resolution. Neutralization of endogenous TRAIL had little effect on G-EAT
      induction, but significantly inhibited G-EAT resolution and increased thyroid
      fibrosis. This correlated with higher expression of pro-inflammatory cytokines
      and preferential expression of the pro-apoptotic molecule TRAIL, and anti
      apoptotic molecules FLIP and Bcl-xL on inflammatory cells in thyroids of anti
      TRAIL-treated recipients. The results suggest that endogenous TRAIL is not
      required for G-EAT development in recipients, but is critical for G-EAT
      resolution. Endogenous TRAIL might promote resolution, at least in part, through
      modulation of the balance between pro- and anti-inflammatory cytokines, and the
      expression pattern of pro- and anti-apoptotic molecules of thyroid epithelial
      cells (TECs) and inflammatory cells.

PMID- 18810760
TI  - Nuclear receptor profile in calvarial bone cells undergoing osteogenic versus
      adipogenic differentiation.
AB  - Nuclear receptors (NRs) are key regulators of cell function and differentiation.
      We examined NR expression during osteogenic versus adipogenic differentiation of
      primary mouse calvarial osteoblasts (MOBs). MOBs were cultured for 21 days in
      osteogenic or adipogenic differentiation media. von Kossa and Oil Red O staining,
      and qRT-PCR of marker genes and 49 NRs were performed. PCR amplicons were
      subcloned to establish correct sequences and absolute standard curves. Forty
      three NRs were detected at days 0-21. Uncentered average linkage hierarchical
      clustering identified four expression clusters: NRs (1) upregulated during
      osteogenic, but not adipogenic, differentiation, (2) upregulated in both
      conditions, with greater upregulation during adipogenic differentiation, (3)
      upregulated equally in both conditions, (4) downregulated during adipogenic, but
      not osteogenic, differentiation. One-way ANOVA with contrast revealed 20 NRs
      upregulated during osteogenic differentiation and 12 NRs upregulated during
      adipogenic differentiation. Two-way ANOVA demonstrated that 18 NRs were higher in
      osteogenic media, while 9 NRs were higher in adipogenic media. The time effect
      revealed 16 upregulated NRs. The interaction of condition with time revealed 6
      NRs with higher expression rate during adipogenic differentiation and 3 NRs with
      higher expression rate during osteogenic differentiation. Relative NR abundance
      at days 0 and 21 were ranked. Basal ranking changed at least 5 positions for 13
      NRs in osteogenic media and 9 NRs in adipogenic media. Osteogenic and adipogenic
      differentiation significantly altered NR expression in MOBs. These differences
      offer a fingerprint of cellular commitment and may provide clues to the
      underlying mechanisms of osteogenic versus adipogenic differentiation.

PMID- 18810761
TI  - Lanthanum enhances in vitro osteoblast differentiation via pertussis toxin
      sensitive gi protein and ERK signaling pathway.
AB  - Converging lines of evidence suggest that lanthanum tends to deposit in bone. The
      influence of lanthanum ion (La3+) on osteoblast differentiation and the related
      mechanism are essential to understanding its effect on bone metabolism. In this
      study, La3+ treatment enhanced in vitro osteoblast differentiation as evidenced
      by promoting alkaline phosphatase (ALP) activity, osteocalcin (OC) secretion, and
      matrix mineralization. The expressions of osteoblast-specific genes of Cbfa-1,
      osteopontin (OPN), and bone sialoprotein (BSP) were all increased in the presence
      of La3+, but no change was observed in that of type I collagen (COL-I). Further
      studies demonstrated that La3+ treatment enhanced phosphorylation of
      extracellular signal-regulated kinase (ERK). Inhibition of ERK activation by
      U0126 suppressed the effects of La3+ on osteoblast activity. Moreover,
      pretreatment of the cells with pertussis toxin (PTx), a Gi protein inhibitor,
      suppressed the La3+-enhanced ERK phosphorylation and osteoblast differentiation.
      These findings suggest that La3+ exposure enhances in vitro osteoblast
      differentiation and the effect depends on ERK phosphorylation via PTx-sensitive
      Gi protein signaling.

PMID- 18810762
TI  - Eight full-length abelson related gene (Arg) isoforms are constitutively
      expressed in caki-1 cell line and cell distribution of two isoforms has been
      analyzed after transfection.
AB  - The human Arg (Abl2) nonreceptor tyrosine kinase has a role in cytoskeletal
      rearrangements by its C-terminal F-actin- and microtubule-binding sequences. We
      have previously identified Arg transcripts with different 5'- and 3'-ends, named
      respectively long and short 1A and 1B (1AL, 1AS, 1BL, 1BS) and long and short C
      termini (CTL and CTS), that have different expression patterns in various cell
      types. The combination of the different ends permits to predict eight putative
      full-length Arg transcripts and corresponding proteins. By Reverse Transcription
      Long PCR we show here that all eight full-length transcripts are endogenously
      expressed in Caki-1 cells and the two bands, approximately 10 kDa different,
      shown by 1-D Western blots of Hek293T and Caki-1 lysates correspond to the full
      length Arg protein isoforms with different C-termini. 2-D Western blot analysis
      evidenced different high molecular weight and slight acidic specific spots in
      Hek293T and Caki-1 lysates. The cellular localization of two Arg isoforms (1BLCTL
      and 1BLCTS) transfected in Caki-1 and Hek293T cells was cytoplasmic, and some
      differences in cytoskeleton interactions have been evidenced. Moreover, in
      Hek293T cells only the transfected 1BLCTS isoform gives rise to a large
      intracytoplasmic cylindrical structure containing phalloidin-positive amorphous
      actin aggregates. The presence of eight full-length Arg isoforms with different
      cellular expression may imply a diverse functional role in normal and neoplastic
      cells.

PMID- 18810763
TI  - Crohnology: a tale of time and times and inflammatory bowel diseases.
AB  - Time, times and timing are key words in inflammatory bowel diseases (IBD). The
      leitmotif of this issue of World Journal of Gastroenterology is time. We have
      asked experts to review on the epidemiology of these diseases over time, the
      changes in innate immunity that could be present in the first time, and then the
      timing of key treatments. The correct time of using azathioprine, mercaptopurine,
      infliximab, cyclosporine and surgery are reviewed. We have chosen experts with
      not only great clinical expertise but also personal interest in clinical and
      basic investigation. Our goal in this monograph is to get an idea not only of the
      present but of the immediate future in some of the key management issues in IBD.
      To this end, we think that the authors are the most adequate.

PMID- 18810764
TI  - Inflammatory bowel diseases: a disease (s) of modern times? Is incidence still
      increasing?
AB  - Inflammatory bowel diseases (IBD) are a heterogeneous group of diseases, not
      always easy to diagnose, even more difficult to classify, and diagnostic criteria
      are not always uniform. Well done population-based studies are not abundant, and
      so comparisons among different geographical areas or populations are not always
      very reliable. In this article, we have reviewed epidemiological studies
      available on the world's population while making a critical review of published
      data.

PMID- 18810765
TI  - Crohn's disease--defect in innate defence.
AB  - Crohn's disease may principally involve the whole gastrointestinal tract. Most
      commonly, the inflammation occurs in the small intestine and/or in the colon with
      stable disease location over the years. The pathogenesis of both disease
      phenotypes is complex, the likely primary defect lies in the innate rather than
      adaptive immunity, particularly in the chemical antimicrobial barrier of the
      mucosa. Crohn's ileitis is associated with a reduced expression of the Wnt
      signalling pathway transcription factor T-cell factor 4 (TCF4), which is
      regulating Paneth cell differentiation. As a result, the alpha-defensins and
      principal Paneth cell products HD5 and HD6 are deficiently expressed in ileal
      disease, independent of current inflammation. In contrast, Crohn's colitis is
      typically associated with an impaired induction of the beta-defensins HBD2 and
      HBD3 caused by fewer gene copy numbers in the gene locus of the beta-defensins on
      chromosome 8. This ileal and colonic defect in innate defence mediated by a
      deficiency of the protective alpha- and beta-defensins may enable the luminal
      microbes to invade the mucosa and trigger the inflammation. A better
      understanding of the exact molecular mechanisms behind ileal and colonic Crohn's
      disease may give rise to new therapeutic strategies based on a stimulation of the
      protective innate immune system.

PMID- 18810766
TI  - Severe ulcerative colitis: at what point should we define resistance to steroids?
AB  - Corticosteroids are still the first-line treatment for active ulcerative colitis
      more than 50 years after the publication of trials assessing their beneficial
      effect, with about a 50% remission rate in cases of severe disease. The mortality
      related to severe attacks of ulcerative colitis has decreased dramatically, to
      less than 1%, in experienced centers, due to the appropriate use of intensive
      therapeutic measures (intravenous steroids, fluids and electrolytes, artificial
      nutritional support, antibiotics, etc), along with timely decision-making about
      second-line medical therapy and early identification of patients requiring
      colectomy. One of the most difficult decisions in the management of severe
      ulcerative colitis is knowing for how long corticosteroids should be administered
      before deciding that a patient is a non-responder. Studies assessing the outcome
      of acute attacks after steroid initiation have demonstrated that, in steroid
      sensitive patients, the response generally occurs early on, in the first days of
      treatment. Different indexes to predict treatment failure, when applied on the
      third day of treatment, have demonstrated a high positive predictive value for
      colectomy. In contrast to this resolute approach, which is the most widely
      accepted, other authors have suggested that in some patients a complete and
      prolonged response to steroids may take longer. Either way, physicians taking
      care of these patients need to recognize that severe ulcerative colitis may be
      life-threatening, and they need to be careful with excessively prolonged medical
      treatment and delayed surgery.

PMID- 18810767
TI  - Treatment of severe steroid refractory ulcerative colitis.
AB  - Although systemic steroids are highly efficacious in ulcerative colitis (UC),
      failure to respond to steroids still poses an important challenge to the surgeon
      and physician alike. Even if the life time risk of a fulminant UC flare is only
      20%, this condition is potentially life threatening and should be managed in
      hospital. If patients fail 3 to 5 d of intravenous corticosteroids and optimal
      supportive care, they should be considered for any of three options: intravenous
      cyclosporine (2 mg/kg for 7 d, and serum level controlled), infliximab (5 mg/kg
      IV, 0-2-6 wk) or total colectomy. The choice between these three options is a
      medical-surgical decision based on clinical signs, radiological and endoscopic
      findings and blood analysis (CRP, serum albumin). Between 65 and 85% of patients
      will initially respond to cyclosporine and avoid colectomy on the short term.
      Over 5 years only 50% of initial responders avoid colectomy and outcomes are
      better in patients naive to azathioprine (bridging strategy). The data on
      infliximab as a medical rescue in fulminant colitis are more limited although the
      efficacy of this anti tumor necrosis factor (TNF) monoclonal antibody has been
      demonstrated in a controlled trial. Controlled data on the comparative efficacy
      of cyclosporine and infliximab are not available at this moment. Both drugs are
      immunosuppressants and are used in combination with steroids and azathioprine,
      which infers a risk of serious, even fatal, opportunistic infections. Therefore,
      patients not responding to these agents within 5-7 d should be considered for
      colectomy and responders should be closely monitored for infections.

PMID- 18810768
TI  - Are we giving azathioprine too late? The case for early immunomodulation in
      inflammatory bowel disease.
AB  - Inflammatory bowel disease (IBD) includes two entities, Crohn's disease and
      ulcerative colitis. Both are chronic conditions with frequent complications and
      surgical procedures and a great impact on patient's quality of life. The
      thiopurine antimetabolites azathioprine and 6-mercaptopurine are widely used in
      IBD patients. Current indications include maintenance therapy, steroid-dependent
      disease, fistula closure, prevention of infliximab immunogenicity and prevention
      of Crohn's disease recurrence. Surprisingly, the wide use of immunosuppressants
      in the last decades has not decreased the need of surgery, probably because these
      treatments are introduced at too late stages in disease course. An earlier use of
      immunosuppressants is now advocated by some authors. The rational includes: (1)
      failure to modify IBD natural history of present therapeutic approach, (2)
      demonstration that azathioprine can induce mucosal healing, a relevant prognostic
      factor for Crohn's disease and ulcerative colitis, and (3) demonstration that
      early immunosuppression has a very positive impact on pediatric, recently
      diagnosed Crohn's disease patients. We are now awaiting the results of new
      studies, to clarify the contribution of azathioprine, as compared to infliximab
      (SONIC Study), and to demonstrate the usefulness of azathioprine in recently
      diagnosed adult Crohn's disease patients (AZTEC study).

PMID- 18810769
TI  - Are we giving azathioprine too much time?
AB  - Azathioprine is currently the key drug in the maintenance treatment of
      inflammatory bowel diseases. However, there are still some practical issues to be
      resolved: one is how long we must maintain the drug. Given that inflammatory
      bowel diseases are to date chronic, non-curable conditions, treatment should be
      indefinite and only the loss of efficacy or the appearance of serious side
      effects may cause withdrawal. As regards to efficacy and their maintenance over
      time, evidence supports the continuous usefulness of the drug in the long term:
      in fact its withdrawal very substantially increases the risk of relapse. About
      side effects, azathioprine is a relatively well tolerated drug and even
      indefinite use seems safe. The main theoretical risks of prolonged use would be
      the myelotoxicity, hepatotoxicity, and the development of cancer. In fact,
      serious bone marrow suppression or serious liver damage are uncommon, and can be
      minimized with proper use of the drug. Recent meta-analysis suggests that the
      risk of lymphoma is real, but the individual risk is rather low, and decision
      analysis suggests a favorable benefit/risk ratio in the long term. Therefore, in
      patients with inflammatory bowel diseases in whom azathioprine is effective and
      well tolerated, the drug should not be stopped. This recommendation concerns the
      use of azathioprine as a single maintenance drug, and is not necessarily
      applicable to patients receiving concomitant biological therapy.

PMID- 18810770
TI  - Are we giving biologics too late? The case for early versus late use.
AB  - Corticosteroids and immunomodulators have been the mainstay therapies for Crohn's
      disease. Corticosteroids are highly effective to control symptoms in the short
      term, but they are not effective in maintaining remission, they heal the mucosa
      in a reduced proportion of cases, and long-time exposure is associated with an
      increased risk of infections and mortality. Immunomodulators, azathioprine and
      methotrexate, heal the mucosa in a higher proportion of patients that
      corticosteroids but their onset of action is slow and they benefit less than half
      of patients with Crohn's disease. In the last decade, medical therapy for Crohn's
      disease has experienced a remarkable change due to the introduction of biologic
      therapy, and particularly the use of anti-tumour necrosis factor-alpha agents.
      Infliximab, adalimumab, and certolizumab pegol have demonstrated efficacy for
      induction and maintenance of remission in active Crohn's disease. These agents
      have raised the bar for what is a suitable symptomatic response in Crohn's
      disease and modification of the natural history of the disease has become a major
      goal in the treatment of Crohn's disease. There are several data in the
      literature that suggest that early use of biologic therapy and achievement of
      mucosal healing contribute to disease course modification. However, many
      questions on early biological therapy for Crohn's disease remain still
      unanswered.

PMID- 18810771
TI  - Are we giving biologics too much time? When should we stop treatment?
AB  - The optimal duration of biological treatment, particularly anti-TNF, in
      inflammatory bowel disease (IBD) is a very important question both for patients
      and physicians. There is no published evidence to clearly and definitely answer
      this question. However data on natural history of IBD, long term safety of
      biologics, immunosuppressors (IS) cessation and some preliminary studies on
      biologics cessation may help us to discuss this topic. The decision to stop a
      biological treatment is currently based on a compromise between the benefits and
      risks associated with the prolongation of this treatment. IBD, more particularly
      CD, are characterized by the development of complications and the need for
      recurrent hospitalizations and surgeries in approximately 2/3 of cases. In these
      patients potentially in need of biological treatments, it is probable that, as it
      has been demonstrated for IS, the longer a stable remission has be achieved under
      treatment, the lower the risk of relapse is after treatment cessation. Further
      prospective studies should now aim at disclosing patient characteristics
      associated with a low risk of relapse to implement this strategy.

PMID- 18810772
TI  - Timing of surgery in Crohn's disease: a key issue in the management.
AB  - The timing of the decision for operation in Crohn's disease is based on an
      evaluation of the several factors such as the failure of medical treatment,
      complications due to the Crohn's disease or to the pharmacological therapy,
      development of dysplasia or cancer and growth retardation. A complete evaluation
      of these factors should result in operation timed to the patient's best
      advantage, achieving maximal relief of symptoms with improvement of quality of
      life. Given the complexity and heterogeneity of the disease and the different
      options for treatment, is difficult to systematize when the optimal moment for
      the surgery is arrived. A very important factor in the management of Crohn's
      disease is the multidisciplinary approach and the patient preference should be a
      significant factor in determining the choice of therapy. The surgery should be
      considered such another option in the sequential treatment of Crohn's disease. We
      have analyzed the factors that are involved in the decision taking of the
      surgical treatment regarding to the experience and the published literature. When
      did the medical therapy fail? when is the appropriate moment to operate on the
      patient? Or which complications of Crohn's disease need surgery? These are some
      of the questions we will try to answer.

PMID- 18810773
TI  - Postoperative Crohn's disease recurrence: a practical approach.
AB  - Crohn's disease is a chronic inflammatory condition that may involve any segment
      of the gastrointestinal tract. Although several drugs have proven efficacy in
      inducing and maintaining disease in remission, resectional surgery remains as a
      cornerstone in the management of the disease, mainly for the treatment of its
      stenosing and penetrating complications. However, the occurrence of new mucosal
      (endoscopic) lesions in the neoterminal ileum early after surgery is almost
      constant, it is followed in the mid-term by clinical symptoms and, in a
      proportion of patients, repeated intestinal resections are required. Pathogenesis
      of postoperative recurrence (POR) is not fully understood, but luminal factors
      (commensal microbes, dietary antigens) seem to play an important role, and
      environmental and genetic factors may also have a relevant influence. Many
      studies tried to identify clinical predictors for POR with heterogeneous results,
      and only smoking has repeatedly been associated with a higher risk of POR.
      Ileocolonoscopy remains as the gold standard for the assessment of appearance and
      severity of POR, although the real usefulness of the available endoscopic score
      needs to be revisited and alternative techniques are emerging. Several drugs have
      been evaluated to prevent POR with limited success. Smoking cessation seems to be
      one of the more beneficial therapeutic measures. Aminosalicylates have only
      proved to be of marginal benefit, and they are only used in low-risk patients.
      Nitroimidazolic antibiotics, although efficient, are associated with a high rate
      of intolerance and might induce irreversible side effects when used for a long
      term. Thiopurines are not widely used after ileocecal resection, maybe because
      some concerns in giving immunomodulators in asymptomatic patients still remain.
      In the era of biological agents and genetic testing, a well-established
      preventive strategy for POR is still lacking, and larger studies to identify good
      clinical, serological, and genetic predictors of early POR as well as more
      effective drugs (or drug combinations) are needed.

PMID- 18810774
TI  - Relationship between nm23H1 genetic instability and clinical pathological
      characteristics in Chinese digestive system cancer patients.
AB  - AIM: To study the relationship between nm23H1 gene genetic instability and its
      clinical pathological characteristics in Chinese digestive system cancer
      patients. METHODS: Polymerase chain reaction-single strand conformation
      polymorphism (PCR-SSCP) was used to analyze the microsatellite instability (MSI)
      and loss of heterozygosity (LOH). Immunohistochemistry was employed to detect the
      expression of nm23H1. RESULTS: The MSI was higher in TNM stage I + II than in
      stage III + IV of gastric, colonic and gallbladder carcinomas. The LOH was higher
      in TNM stage III + IV than in stage I + II of gastric, colonic and hepatocellular
      carcinomas. Lymphatic metastasis was also observed. The expression of nm23H1
      protein was lower in TNM stage III + IV than in stage I + II of these tumors and
      in patients with lymphatic metastasis.The nm23H1 protein expression was higher in
      the LOH negative group than in the LOH positive group. CONCLUSION: MSI and LOH
      may independently control the biological behaviors of digestive system cancers.
      MSI could serve as an early biological marker of digestive system cancers.
      Enhanced expression of nm23H1 protein could efficiently inhibit cancer metastasis
      and improve its prognosis. LOH mostly appears in late digestive system cancer.

PMID- 18810775
TI  - Gene expression and MR diffusion-weighted imaging after chemoembolization in
      rabbit liver VX-2 tumor model.
AB  - AIM: To investigate the dynamic characteristics and the correlation between PCNA,
      Bax, nm23, E-cadherin expression and apparent diffusion coefficient (ADC) on MR
      diffusion-weighted imaging (DWI) after chemoembolization in rabbit liver VX-2
      tumor model. METHODS: Forty New Zealand rabbit liver VX-2 tumor models were
      included in the study. DWI was carried out periodically after chemoembolization.
      All VX-2 tumor samples in each group were examined by histopathology and Strept
      Avidin-Biotin Complex (SABC) immunohistochemical staining. RESULTS: The PCNA
      expression index in VX-2 tumors was higher than in the normal parenchyma around
      the tumor (P < 0.001). Nm23, Bax or E-caderin expression index in VX-2 tumors
      were lower than in the normal parenchyma around the tumor (all P < 0.001). PCNA
      and nm23 expression in the VX-2 tumor periphery first increased and then
      decreased (P < 0.001 and P = 0.03, respectively), while the expression of Bax and
      E-cadherin before and after chemoembolization was insignificant. When b-value was
      100 s/mm(2), there was a linear correlation between PCNA expression and ADC in
      the area of VX-2 tumor periphery (P < 0.001), and PCNA expression in VX-2 tumor
      periphery influenced the ADC. CONCLUSION: The potential of VX-2 tumor
      infiltrating and metastasizing decreases, while its ability to proliferate
      increases for a short time after chemoembolization. To some degree, the ADC value
      indirectly reflects the proliferation of VX-2 tumor cells.

PMID- 18810776
TI  - Interferon-alpha restrains growth and invasive potential of hepatocellular
      carcinoma induced by hepatitis B virus X protein.
AB  - AIM: To investigate the effects of interferon-alpha (IFN-alpha) to restrain the
      growth and invasive potential of hepatocellular carcinoma (HCC) induced by
      hepatitis B virus (HBV) X protein. METHODS: The pcDNA3.1-HBx plasmid was
      transfected into Chang cells by Lipofectamine in vitro, and Chang/HBx was co
      cultured with IFN-alpha. Cell survival growth curve and clonogenicity assay were
      used to test the growth potential of Chang/pcDNA3.1, Chang/HBx and IFN-alpha
      Chang/HBx in vitro. Growth assay in nude mice was used to detect the growth
      potential of Chang/pcDNA3.1, Chang/HBx and IFN-alpha-Chang/HBx in vivo. Wound
      healing and transwell migration assays were used to detect the invasive ability
      of Chang/pcDNA3.1, Chang/HBx and IFN-alpha-Chang/HBx. RESULTS: Compared with
      CCL13 cells transfected with pcDNA3.1, CCL13 with stable expression of hepatitis
      B virus X protein showed the characteristics of malignant cells with high
      capability of growth and invasion by detecting their growth curves, colony
      forming efficiency, wound healing , transwell migration assays and growth assays
      in nude mice. Its capability of growth and invasion could be controlled by IFN
      alpha. CONCLUSION: IFN-alpha can restrain the growth and invasive potential of
      HCC cells induced by HBx protein, which has provided an experimental basis for
      IFN-alpha therapy of HCC.

PMID- 18810777
TI  - Potentially probiotic bacteria induce efficient maturation but differential
      cytokine production in human monocyte-derived dendritic cells.
AB  - AIM: To analyze the ability of nine different potentially probiotic bacteria to
      induce maturation and cytokine production in human monocyte-derived dendritic
      cells (moDCs). METHODS: Cytokine production and maturation of moDCs in response
      to bacterial stimulation was analyzed with enzyme-linked immunosorbent assay
      (ELISA) and flow cytometric analysis (FACS), respectively. The kinetics of mRNA
      expression of cytokine genes was determined by Northern blotting. The involvement
      of different signaling pathways in cytokine gene expression was studied using
      specific pharmacological signaling inhibitors. RESULTS: All studied bacteria
      induced the maturation of moDCs in a dose-dependent manner. More detailed
      analysis with S. thermophilus THS, B. breve Bb99, and L. lactis subsp. cremoris
      ARH74 indicated that these bacteria induced the expression of moDC maturation
      markers HLA class II and CD86 as efficiently as pathogenic bacteria. However,
      these bacteria differed in their ability to induce moDC cytokine gene expression.
      S. thermophilus induced the expression of pro-inflammatory (TNF-alpha, IL-12, IL
      6, and CCL20) and Th1 type (IL-12 and IFN-gamma) cytokines, while B. breve and L.
      lactis were also potent inducers of anti-inflammatory IL-10. Mitogen-activated
      protein kinase (MAPK) p38, phosphatidylinositol 3 (PI3) kinase, and nuclear
      factor-kappa B (NF-kappaB) signaling pathways were shown to be involved in
      bacteria-induced cytokine production. CONCLUSION: Our results indicate that
      potentially probiotic bacteria are able to induce moDC maturation, but their
      ability to induce cytokine gene expression varies significantly from one
      bacterial strain to another.

PMID- 18810778
TI  - Fecal markers of inflammation used as surrogate markers for treatment outcome in
      relapsing inflammatory bowel disease.
AB  - AIM: To evaluate fecal calprotectin (FC) as a surrogate marker of treatment
      outcome of relapse of inflammatory bowel disease (IBD) and, to compare FC with
      fecal myeloperoxidase (MPO) and fecal eosinophil protein X (EPX). METHODS: Thirty
      eight patients with IBD, comprising of 27 with ulcerative colitis (UC) and 11
      with Crohn's disease (CD) were investigated before treatment (inclusion), and
      after 4 and 8 wk of treatment. Treatment outcomes were evaluated by clinical
      features of disease activity and endoscopy in UC patients, and disease activity
      in CD patients. In addition, fecal samples were analyzed for FC by enzyme-linked
      immunosorbent assay (ELISA), and for MPO and EPX with radioimmunoassay (RIA).
      RESULTS: At inclusion 37 of 38 (97%) patients had elevated FC levels (> 94.7
      microg/g). At the end of the study, 31 of 38 (82%) patients fulfilled predefined
      criteria of a complete response [UC 21/27 (78%); CD 10/11 (91%)]. Overall, a
      normalised FC level at the end of the study predicted a complete response in 100%
      patients, whereas elevated FC level predicted incomplete response in 30%.
      Normalised MPO or EPX levels predicted a complete response in 100% and 90% of the
      patients, respectively. However, elevated MPO or EPX levels predicted incomplete
      response in 23% and 22%, respectively. CONCLUSION: A normalised FC level has the
      potential to be used as a surrogate marker for successful treatment outcome in
      IBD patients. However, patients with persistent elevation of FC levels need
      further evaluation. FC and MPO provide superior discrimination than EPX in IBD
      treatment outcome.

PMID- 18810779
TI  - Resection and primary anastomosis with or without modified blow-hole colostomy
      for sigmoid volvulus.
AB  - AIM: To evaluate the efficacy of resection and primary anastomosis (RPA) and RPA
      with modified blow-hole colostomy for sigmoid volvulus. METHODS: From March 2000
      to September 2007, 77 patients with acute sigmoid volvulus were treated. A total
      of 47 patients underwent RPA or RPA with modified blow-hole colostomy. Twenty
      five patients received RPA (Group A), and the remaining 22 patients had RPA with
      modified blow-hole colostomy (Group B). The clinical course and postoperative
      complications of the two groups were compared. RESULTS: The mean hospital stay,
      wound infection and mortality did not differ significantly between the groups.
      Superficial wound infection rate was higher in group A (32% vs 9.1%). Anastomotic
      leakage was observed only in group A, with a rate of 6.3%. The difference was
      numerically impressive but was statistically not significant. CONCLUSION: RPA
      with modified blow-hole colostomy provides satisfactory results. It is easy to
      perform and may become a method of choice in patients with sigmoid volvulus.
      Further studies are required to further establish its role in the treatment of
      sigmoid volvulus.

PMID- 18810780
TI  - Pancreatic guidewire placement for achieving selective biliary cannulation during
      endoscopic retrograde cholangio-pancreatography.
AB  - AIM: To investigate the frequency and risk factors for acute pancreatitis after
      pancreatic guidewire placement (P-GW) in achieving cannulation of the bile duct
      during endoscopic retrograde cholangio-pancreatography (ERCP). METHODS: P-GW was
      performed in 113 patients in whom cannulation of the bile duct was difficult. The
      success rate of biliary cannulation, the frequency and risk factors of post-ERCP
      pancreatitis, and the frequency of spontaneous migration of the pancreatic duct
      stent were investigated. RESULTS: Selective biliary cannulation with P-GW was
      achieved in 73% of the patients. Post-ERCP pancreatitis occurred in 12% (14
      patients: mild, 13; moderate, 1). Prophylactic pancreatic stenting was attempted
      in 59% of the patients. Of the 64 patients who successfully underwent stent
      placement, three developed mild pancreatitis (4.7%). Of the 49 patients without
      stent placement, 11 developed pancreatitis (22%: mild, 10; moderate, 1). Of the
      five patients in whom stent placement was unsuccessful, two developed mild
      pancreatitis. Univariate and multivariate analyses revealed no pancreatic
      stenting to be the only significant risk factor for pancreatitis. Spontaneous
      migration of the stent was observed within two weeks in 92% of the patients who
      had undergone pancreatic duct stenting. CONCLUSION: P-GW is useful for achieving
      selective biliary cannulation. Pancreatic duct stenting after P-GW can reduce the
      incidence of post-ERCP pancreatitis, which requires evaluation by means of
      prospective randomized controlled trials.

PMID- 18810781
TI  - Prolapse gastropathy syndrome may be a predictor of pathologic acid reflux.
AB  - AIM: To assess the occurrence of gastric acid reflux into the esophagus in
      endoscopically confirmed prolapse gastropathy syndrome (PGS). METHODS: Using
      ambulatory esophageal pH measurement (BRAVO(TM) wireless esophageal pH monitoring
      system), twenty-six patients with PGS were compared with twenty-one patients with
      erosive esophagitis (EE) as controls. We assessed several reflux parameters,
      including the percentage of total time at pH < 4, and the DeMeester score.
      RESULTS: There were no statistical differences between the PGS group and the EE
      group as to mean age, sex ratio and pH recording time. The EE group showed more
      severe reflux than the PGS group, as evaluated in terms of the longest duration
      of reflux, the number of reflux episodes, the number of reflux episodes lasting >
      5 min, the total time with pH < 4 during acid reflux episodes, and the DeMeester
      score, but none of these parameters showed statistically significant difference.
      Although 53.8% (14/26) of the PGS group and 76.2% (16/21) of the EE group
      demonstrated pathologic acid reflux (DeMeester score > 14.72), there was no
      statistically significant difference between the two groups in the incidence of
      pathologic acid reflux (P = 0.11). CONCLUSION: There was no statistically
      significant difference in pathologic acid reflux between the PGS and EE group.
      These data suggest that endoscopically diagnosed PGS might be a predictor of
      pathologic acid reflux.

PMID- 18810782
TI  - Tumor suppress genes screening analysis on 4q in sporadic colorectal carcinoma.
AB  - AIM: To search candidate tumor suppressor genes (TSGs) on chromosome 4q through
      detecting high loss of heterozygosity (LOH) regions in sporadic colorectal
      carcinoma in Chinese patients. METHODS: Thirteen fluorescent labeled polymorphic
      microsatellite markers were analyzed in 83 cases of colorectal carcinoma and
      matched normal tissue DNA by polymerase chain reaction (PCR). PCR products were
      electrophoresed on an ABI 377 DNA sequencer. Genescan 3.7 and Genotype 3.7
      software were used for LOH scanning and analysis. Comparison between LOH
      frequency and clinicopathological factors were performed by c2 test. RESULTS:
      Data were collected on all informative loci. The average LOH frequency on 4q was
      28.56%. The D4S2915 locus showed highest LOH frequency (36.17%). Two obvious
      deletion regions were detected: one between D4S3000 and D4S2915 locus (4q12
      21.1), another flanked by D4S407 and D4S2939 locus (4q25-31.1). None case showed
      complete deletion of 4q, most cases displayed interstitial deletion pattern
      solely. Furthermore, compared with clinicopathological features, a significant
      relationship was observed between LOH frequencies on D4S3018 locus. In tumors
      larger than 5 cm in diameter, LOH frequency was significantly higher than tumors
      that were less than 5 cm (56% vs 13.79%, P = 0.01). On D4S1534 locus, LOH was
      significantly associated with liver metastasis (80% vs 17.25%, P = 0.012). No
      relationship was detected on other locus compared with clinicopathological
      features. CONCLUSION: By high resolution deletion mapping, two high frequency
      regions of LOH (4q12-21.1 and 4q25-31.1) were detected, which may contribute to
      locate TSGs on chromosome 4q involved in carcinogenesis and progression of
      sporadic colorectal carcinoma.

PMID- 18810783
TI  - Coffee drinking lowers mortality risk in women.

PMID- 18810785
TI  - The building blocks of health reform: achieving universal coverage and health
      system savings.
AB  - The presidential election has focused public attention on the need for health
      system reform--to ensure health insurance for all, to make health care more
      accessible and responsive to patients, and to slow the growth in health care
      cost. This issue brief sets forth a framework for expanding health coverage that
      offers Americans a choice of a product modeled on Medicare to those under age 65,
      made available through a national insurance connector. Coupled with reforms to
      Medicare provider payment, expansion of preventive health care, and improved
      information, such a strategy has the potential to achieve near-universal coverage
      and improve quality and access, while generating health system savings of $1.6
      trillion over 10 years.

PMID- 18810786
TI  - Protein kinase CK2, cystic fibrosis transmembrane conductance regulator, and the
      deltaF508 mutation: F508 deletion disrupts a kinase-binding site.

PMID- 18810784
TI  - The Declaration of Istanbul on organ trafficking and transplant tourism.

PMID- 18810787
TI  - Linezolid resistant enterococcus faecium.

PMID- 18810788
TI  - [The regional medical demographic characteristics in the Russian Federation].
AB  - The analysis of the aspects of demographic situation in several regions of the
      Russian Federation is made to determine the divergence of levels of life
      expectancy from 1998 to 2005. The key role of the male premature mortality in
      this respect is demonstrated. The contradiction of the revealed trends with the
      logic of development of resources supply and volumes of provided medical care is
      explained.

PMID- 18810789
TI  - [The issues of the medical social rehabilitation of the handicapped persons of
      able-bodied age].
AB  - Among the medical social and economic problems having important universal public
      significance, a particular place belongs to the issues of the disability and the
      organization of care of persons with limited physical and mental possibilities.
      The Nijhny Novgorod oblast experience of work with the handicapped persons
      demonstrates that in the large-scale industrial region the level of disability is
      rather high with the neatly marked tendency to increase. The need for the
      professional education and further employment assistance is quite meaningful
      among the handicapped persons of able-bodied age. To meet this demand is possible
      only on the way of the development of the system of professional rehabilitation
      on the oblast level. The most appropriate conditions for the professional
      rehabilitation of the young handicapped persons are established in the special
      purpose professional specialized schools where the rehabilitation divisions are
      deployed. This approach allows to work effectively on the implementation of the
      individual programs of handicapped persons rehabilitation and in that way to
      provide a higher level of social security of the students (i.e. higher
      scholarship, free-of-charge meals and medical services). In the city of Nijhny
      Novgorod specialized boarding school for the handicapped persons a system of
      activities is developed to enhance the social adaptation including the blocks of
      labor and everyday life adaptation and practical work training.

PMID- 18810790
TI  - [The mortality of the able-bodied population in the Irkutsk oblast].
AB  - The comprehensive evaluation of the irrevocable demographic losses among the able
      bodied population in Irkutsk oblast. The quantitative structural analysis was
      implemented as applied to the characteristics of mortality of this population
      contingent. The peculiarities of formation of the vital potential of the
      economically active population. The structure and hierarchy of factors
      conditioning the worst losses of vital potential

PMID- 18810791
TI  - [About the conditions of training and retraining of physicians and nurse
      personnel for the primary medical sanitary care].

PMID- 18810792
TI  - [The comparative evaluation of personnel supply for public health].

PMID- 18810793
TI  - [The involvement of the Russian Red Cross Society in caring the wounded during
      the British Boer war 1899-1902].

PMID- 18810794
TI  - [Transfusion-related acute lung injury (TRALI) in the Netherlands in 2002-2005].

PMID- 18810795
TI  - Contaminated heparin.

PMID- 18810796
TI  - Femoral venous catheterization.

PMID- 18810797
TI  - Early immune response against retrovirally transduced herpes simplex virus
      thymidine kinase-expressing gene-modified T cells coinfused with a T cell
      depleted marrow graft: an altered immune response?
AB  - Administration of herpes simplex thymidine kinase (HSV-tk)-expressing, gene
      modified T cells (GMCs) with T cell-depleted bone marrow transplantation (TCD
      BMT) can allow modulation of posttransplantation alloreactivity. Twelve patients
      received 2 x 10(5) to 2 x 10(6) CD3+ donor GMCs per kilogram with HLA-identical
      sibling TCD-BMT. Despite extensive T cell depletion of bone marrow, an intensive
      conditioning regimen, and immunosuppressive graft-versus-host disease (GvHD)
      prophylaxis, infusion at the time of TCD-BMT of this low number of GMCs sufficed
      to induce a rapid GMC-specific immune response, as detected by interferon- enzyme
      linked immunospot assay in six of eight patients, preferentially targeting HSV
      tk. Maximal responses were reached early (median time, 49 [35-68] days post-BMT),
      with a subsequent rapid and significant decrease in five of six evaluable
      patients. Immune responses were negatively correlated with the maximal
      circulating GMC counts. However, such immune response did not result in the
      elimination of circulating GMCs and was not associated with measurable ex vivo
      cytotoxic activity against GMCs. Furthermore, alloreactive GMCs still could
      induce GCV-sensitive GvHD in one patient despite an ongoing immune response.
      Overall, infusion of HSV-tk-expressing GMCs at the time of BMT results in an
      early immune response. Such immune response may be altered and may not prevent
      persistent GCV-sensitive alloreactivity.

PMID- 18810798
TI  - Readers appreciate JAVMA commentary on good medicine.

PMID- 18810799
TI  - Tumor-targeted radionuclide imaging and therapy based on human sodium iodide
      symporter gene driven by a modified telomerase reverse transcriptase promoter.
AB  - Human telomerase reverse transcriptase (hTERT) is highly active in most cancer
      cells and, thus, could be used for tumor targeting. The human sodium iodide
      symporter (hNIS) gene is being actively researched as a potential radioactive
      iodine (radioiodine) gene therapy. In this study, we investigated the
      possibilities of using the hNIS gene driven by the hTERT promoter for molecular
      imaging and radioiodine gene therapy. Stable cell lines of hTERT-positive cells
      (Hep3B hepatoma) expressing hNIS, under the control of the 5mmTERT promoter, were
      generated using a retroviral system. Radioiodine uptake and efflux tests were
      performed, and a clonogenic assay was used to evaluate the in vitro cytotoxicity
      of 131I. Finally, scintigraphic, biodistribution, and radioiodine therapy studies
      were performed in vivo. Radioiodine uptake by 5mmTERT-NIS-transfected Hep3B cells
      was 22 times higher than by nontransfected Hep3B cells, and 5 times that of
      5mmTERT-NIS-transfected U2-OS cells (p < 0.05). Clonogenic assays demonstrated
      that the survival rate of Hep3B-5mmTERT-NIS cells after 131I incubation was
      significantly lower than that of Hep3B cells (p < 0.001), and radioiodine
      accumulations in Hep3B-5mmTERT-NIS tumors were significantly higher than in wild
      type tumors. In addition, technetium- 99m scintigraphy clearly visualized Hep3B
      5mmTERT-NIS tumors. Moreover, after being treated with 111 MBq of 131I-labeled
      Hep3B-5mmTERT-NIS, tumor growth was retarded, whereas Hep3B tumor growth
      progressed. hTERT-positive tumors were successfully targeted by the NIS gene
      under the control of the 5mmTERT promoter. The described system could be useful
      for targeted molecular imaging and as a radioiodine gene therapy for cancer.

PMID- 18810800
TI  - TRPA1-mediated nociception.

PMID- 18810801
TI  - TRPA1-mediated nociception: response to letter by Fischer et al.

PMID- 18810802
TI  - US to debate tightening legislation on safety of chemicals.

PMID- 18810803
TI  - Predicting the next pandemic.

PMID- 18810804
TI  - Asthma, illness, and identity.

PMID- 18810805
TI  - Three-dimensional finite element analysis of the application  of attachment for
      obturator framework in unilateral  maxillary defect.
AB  - AIMS: The aim of this study was to evaluate the stress on the abutment teeth and
      framework ina unilateral maxillary defect which was restored by an obturator
      retained by resin-bonded extra coronal attachment. METHODS: A three-dimensional
      finite element model of the human unilateral maxillary defect was constructed.
      Traditional obturator framework with four casting circumferential clasp was
      established (model 1). A continuous lingual guide plane of 0.5 mm thickness on
      all of the remaining teeth, with Mini-SG/F attachment on the mesial surface of
      the central incisor was also established (model 2). The modelling and analytical
      processes were performed using the ANSYS technologies. RESULTS: Stress was
      transmitted to the anterior part of the palate, with stress values being lower on
      the anterior teeth compared with the posteriors. The highest stress value of
      model 1 and model 2 was 13.1 Mpa, 19.9 Mpa respectively. Stress concentrations
      were found at the junction of the attachment to the lingual guide plane and the
      anterior part of the lingual plane. CONCLUSION: The results of this study suggest
      that the application of a resin-bonded extra coronal attachment for obturator
      retention is in accordance with the design principles for the restorative
      treatment of maxillary defects.The design of the attachment framework needs to be
      further investigated. Benefit can be gained by splinting the abutment teeth.

PMID- 18810806
TI  - Uncontrolled asthma means missed work and school, emergency department visits for
      many Californians.
AB  - In 2005, three million Californians reported that they had current asthma.
      Despite advances in therapy, asthma remains a disease that is not optimally
      controlled in many Californians. Inadequately controlled asthma can result in
      missed work and school and emergency department visits. Asthma was responsible
      for an estimated 1.9 million missed days of school and two million days of missed
      work in California in 2005. In addition, more than 475,000 children and adults in
      California went to the emergency department or urgent care center because of
      asthma. There are 659,000 children and adults who suffer from asthma symptoms
      every day or every week (22% of those with current asthma). These Californians
      suffering from frequent asthma symptoms have higher rates of missing school or
      work due to their asthma, visiting the emergency department or urgent care for
      their asthma, and rating their overall health as fair or poor. Improvements in
      access to health care, asthma management and avoidance of triggers can help these
      Californians reduce the severity of their asthma burden. Using data from the 2005
      California Health Interview Survey (CHIS 2005), this policy brief examines the
      burden associated with frequent asthma symptoms among those with current asthma,
      and identifies key opportunities for reducing and controlling disease activity in
      these asthma sufferers. Asthma is a chronic disease that causes the airways of
      the lungs to become inflamed and more sensitive to constriction, making it harder
      to breathe. Current asthma refers to people who have been diagnosed with asthma
      and who report they still have asthma, or have had an episode or attack in the
      previous year. Frequent asthma symptoms are defined as experiencing asthma
      symptoms every day or every week.

PMID- 18810807
TI  - Another perspective on veterinarians in public health.

PMID- 18810808
TI  - Medicine needs a spiritual dimension.

PMID- 18810809
TI  - Immunohistochemistry: some more benefits.

PMID- 18810810
TI  - Letter from Mumbai.

PMID- 18810811
TI  - [Clinical reasoning and decision-making in practice. A man with hip pain and
      fever].

PMID- 18810812
TI  - Change of plans. Squeezed by soaring medical costs and other demands for their
      revenue, providers are continuing to sell off their health plans.
AB  - More systems are deciding to get out of the health insurance business, pushed by
      higher medical costs and increasing demands for construction and IT projects.
      It's a climate that can be tough for smaller organizations. "The system needs a
      very good demographic and a strong balance sheet to support both the provider
      side and the health plan side," says Eva Sverdlova, left, an analyst at A.M.
      Best.

PMID- 18810813
TI  - GOP spotlight passes healthcare. Republicans give little mention to industry,
      policy issues at convention.

PMID- 18810814
TI  - Grassley queries two hospitals. Michelle Obama's employer is now under review.

PMID- 18810815
TI  - Moody's to adopt revised scale. Average increase for healthcare industry, one
      notch.

PMID- 18810816
TI  - Tell me, is this right? Docs looking for PQRI feedback: MGMA survey.

PMID- 18810817
TI  - Gustav becomes a test spin. Some say more federal capital needed for rainier
      days.

PMID- 18810818
TI  - Vote pro-medicine.

PMID- 18810819
TI  - Invasion of Georgia.

PMID- 18810820
TI  - Doc ownership takes legal hit. The dismissal of Little Rock Cardiology Clinic's
      antitrust case against Baptist Health could create roadblocks for physician
      groups, some suggest.
AB  - When a federal judge in Arkansas tossed out an antitrust complaint, hospitals
      nationwide got some legal guidance on fighting physician-owned specialty
      hospitals. The court "ultimately boiled down to a simple, logical conclusion: A
      hospital cannot monopolize a market in which it doesn't offer a product," says
      general counsel for the Federation of American Hospitals Jeffrey Micklos, left.

PMID- 18810821
TI  - Providers: more pay in P4P. CMS says higher incentive opportunities possible.

PMID- 18810822
TI  - Medtronic unwraps gifts. But some say vendor's role not clearly defined.

PMID- 18810824
TI  - Clarian expanding ... to possibly Indiana's largest system.

PMID- 18810823
TI  - Vestiges of the boom. Not-for-profit portfolios saw average 8% gain in '07.

PMID- 18810825
TI  - Sticking to the basics. More systems are learning that they can't be both
      providers and insurers.

PMID- 18810826
TI  - By the numbers. Largest post-acute-care companies.

PMID- 18810827
TI  - [Apo-E, C-reactive protein, and apolipoprotein (A) are vector proteins for
      transfer of fatty acids to loose connective tissue cells at the stages of
      inflammation syndrome and in mutations].

PMID- 18810828
TI  - [Feasibilities of laboratory diagnosis of cognitive disorders in dyscirculatory
      encephalopathy].
AB  - A hundred and sixty-nine patients aged 51-80 years who had Stages I and II
      dyscirculatory encephalopathy were examined. A control group comprised 32
      apparently healthy individuals of the same age. Cognitive disorders were rated
      using the mini-mental state examination (MMSE) scale. The serum activities of
      butyrylcholine esterase (BCE) and gamma-glutamyl transferase (gamma-GT) were
      studied. The development of moderate cognitive disorders was found to be
      accompanied by lower BCE and higher gamma-GT activities. The activity levels of
      these enzymes may be used as markers reflecting the cholinergic and glutamatergic
      neuromediatory systems involved in cognitive functions.

PMID- 18810829
TI  - [Variability of quantitative changes in short-chain fatty acids in serum and
      epidermis in psoriasis].
AB  - Gas liquid chromatography was used to study the spectrum of short-chain fatty
      acids (SCFA) in the serum and epidermal corneal layers of abnormal and apparently
      healthy skin areas in patients with psoriatic disease on an exacerbation and at a
      progressive stage. Significantly lower SCFA levels were detected in both
      psoriatic and intact areas, with derangements being mostly manifested in the
      papulae. There were heterodirectional serum volatile fatty acid spectrum changes
      that were characterized by a rise in the concentrations of isobutyrate,
      valeriate, and capronate and by a decrease in the proportion of acetate and
      propionate.

PMID- 18810830
TI  - [Changes in coagulation hemostasis in patients after coronary bypass surgery].
AB  - Changes in the coagulation link of hemostasis were studied in 37 patients who had
      undergone coronary bypass surgery using venous and arterial conduits and in 16
      healthy individuals of the same age. The recordings of hemostasiograms were
      examined before and 14 days after surgery. Prior to coronary bypass surgery, the
      patients with ischemic heart disease were found to have coagulation hemostatic
      disorders as moderate hyperfibrinogenemia, fibrinolytic suppression,
      thrombinemia, and elevated D-dimer concentrations. Postoperatively,
      hypercoagulation substantially increased with suppressed fibrinolysis and
      decreased anticoagulants in the protein C system. In this connection, it is
      necessary to longer use anticoagulants in the postoperative period and to
      thoroughly monitor hemostasiogram recordings after their discontinuance.

PMID- 18810831
TI  - [Role of lipid peroxidation in aggregation of blood cells in burn disease].
AB  - Spontaneous aggregation of erythrocytes and platelets was studied in burn injury.
      The plasma from burnt patients was ascertained to significantly increase blood
      cell aggregation in healthy individuals. It was shown that a-tocopherol-induced
      decreases in the rate of lipid peroxidation in plasma reduced its aggregatory
      activity to only a small extent. This suggests that antioxidant therapy is lowly
      effective in treating microcirculatory disorders in bum injury.

PMID- 18810832
TI  - [A history of the Renam Company].

PMID- 18810833
TI  - [National Standard of the Russian Federation. Cytological study of bone marrow
      puncture specimens ( a draft)].

PMID- 18810834
TI  - Muslim girls may miss out on cervical cancer immunisation.

PMID- 18810835
TI  - Charity plan to keep PFI debts off NHS trusts' balance sheets.

PMID- 18810836
TI  - Government to bail out failing hospitals.

PMID- 18810837
TI  - Experts get snagged on health's thorniest issue.

PMID- 18810838
TI  - Simon Stevens on putting a price on life.

PMID- 18810839
TI  - Get happy: the secret to a healthy old age.

PMID- 18810840
TI  - Data briefing. Quality measures obscure real picture.

PMID- 18810841
TI  - Smells like teen spirit.
AB  - A third of the world's population is under 18. Adolescents are less likely than
      any other age group to visit their GP. Puberty can have an effect on long-term
      conditions.

PMID- 18810842
TI  - Patient involvement. Parlez-vous health?

PMID- 18810843
TI  - Leadership. The inside track.

PMID- 18810844
TI  - [Quality aspects of lipid accumulation in insulin resistance--a lesson from long
      fatty acid elongase, Elovl-6].

PMID- 18810845
TI  - Clinical study of cutaneous drug eruptions in 200 patients.
AB  - BACKGROUND: Cutaneous drug reactions are the most common adverse reactions
      attributed to drugs. Any skin disorder can be imitated, induced or aggravated by
      drugs. AIMS: The present study was carried out to determine the age, sex
      incidence and clinical pattern of drug eruptions, to recognize offending drugs
      (self medication or prescribed), to evaluate mortality and morbidity associated
      with drugs, to educate the patients, and to avoid self-administration of drugs
      and re-administration of the offending drugs. METHODS: The diagnosis of cutaneous
      drug reactions is mainly based on detailed history and correlation between drug
      intake and the onset of rash. Two hundred patients (112 males and 88 females)
      presenting with cutaneous drug reactions were studied. RESULTS: Fixed drug
      eruption was seen in 61 patients; others being urticaria and angioedema,
      morbilliform rash in 37, pruritus in 25, Stevens Johnson (SJ) syndrome in six,
      purpura in six, exfoliative dermatitis in five, photosensitivity in five, Toxic
      Epidermal Necrolysis in two, acneiform eruption in three, and erythema multiforme
      in two patients. The most frequently affected age group was 41-50 years, followed
      by the 21-30 and 31-40 years age groups. The youngest patient was one year old
      and the oldest was 80 years old. The period of development of lesions after the
      intake of drug(s) varies from 01-45 days. Cotrimoxazole was the offending drug in
      26 cases, followed by Ibuprofen in 20 cases. CONCLUSIONS: Fixed drug eruption was
      the most common drug eruption seen. Cotrimoxazole was the most common cause of
      drug eruptions.

PMID- 18810846
TI  - Contact dermatitis in Wood workers.

PMID- 18810847
TI  - Transcription of rDNA insertions in bobbed mutants of Drosophila melanogaster.

PMID- 18810848
TI  - A hidden cost of happiness in children.
AB  - Happiness is generally considered an emotion with only beneficial effects,
      particularly in childhood. However, there are some situations where the style of
      information processing triggered by happiness could be a liability. In
      particular, happiness seems to motivate a top-down processing style, which could
      impair performance when attention to detail is required. Indeed, in Experiment 1,
      10- to 11-year-old children (N = 30) induced to feel a happy mood were slower to
      locate a simple shape embedded in a complex figure than those induced to feel a
      sad mood. In Experiment 2, 6- to 7-year-old children (N = 61) induced to feel a
      happy mood found fewer embedded shapes than those induced to feel a sad or
      neutral mood. Happiness may have unintended and possibly undesirable cognitive
      consequences, even in childhood.

PMID- 18810849
TI  - A day in the life of Bagdad's Ibn Sina Hospital.

PMID- 18810850
TI  - Environmental stimulation, parental nurturance and cognitive  development in
      humans.
AB  - The effects of environmental stimulation and parental nurturance on brain
      development have been studied extensively in animals. Much less is known about
      the relations between childhood experience and cognitive development in humans.
      Using a longitudinally collected data set with ecologically valid in-home
      measures of childhood experience and later in-laboratory behavioral measures of
      cognitive ability, we were able to test hypotheses concerning the effects of
      environmental stimulation and parental nurturance. A double dissociation was
      found: On the one hand, there was a selective relation between parental
      nurturance and memory development, consistent with the animal literature on
      maternal buffering of stress hormone effects on hippocampal development. On the
      other hand, there was a selective relation between environmental stimulation and
      language development. The relevance of these findings to socioeconomic gradients
      in cognitive ability is discussed.

PMID- 18810851
TI  - [Fibronectin gene polymorphisms and clinical manifestations of mixed
      cryoglobulinemic syndrome: increased risk of lymphoma associated to MspI DD and
      HaeIII AA genotypes].
AB  - OBJECTIVE: To analyse FN gene polymorphisms in type II mixed cryoglobulinemic
      syndrome (MCsn), an immune-complex mediated systemic vasculitis linked to
      hepatitis C virus (HCV) infection and characterized by rheumatoid factor (RF)
      positive B-cell proliferation at high risk for the progression into non Hogkin's
      lymphoma (NHL). METHODS: Samples from eighty-one patients, with MCsn (type II
      serum cryoglobulins and clinical signs of vasculitis were studied. Sixty-five
      (65/81, 80.3%) patients were HCV-positive. Twenty-one (25.9%) patients had
      developed a B-cell NHL during the course of MCsn. Seventy-two patients with HCV
      negative and MC-unrelated NHL and 110 healthy blood donors (HBDs) were taken as
      controls. HaeIIIb and MspI FN gene polymorphisms were analysed by ELISA, whenever
      possible. RESULTS: HaeIIIb and MspI allele and genotypic frequencies did not
      differ between MCsn patients and HBDs. Of note, the DD-MspI allele and genotype
      frequencies did not differ between MCsn patients and HBDs. Of note, the DD-MspI
      (OR = 5.56; DI = 1.67-18.51, p = 0.0046) and the AA-HaeIIIb (OR = 5.54, CI = 1.64
      18.76, p = 0.0066) homozygosis appeared significantly and independently
      associated with the development of B-cell NHL in MCsn patients, with the HaeIIIbA
      allele possibly conferring an increased risk of NHL in the general population (OR
      = 1.72, CI = 1.128-2.635, p = 0.0133). In contrast, the major vasculitic
      manifestations, such as peripheral neuropathy, skin ulcers and glomerulonephritis
      tended to be associated with the counterpart MspI C allele. No association
      between FN plasma levels and FN genotypes was found. CONCLUSION: Genotyping for
      MspI and HaeIIIb FN gene polymorphisms may be clinically relevant to define the
      predisposition to the major clinical manifestations in MCsn.

PMID- 18810852
TI  - Coagulation factors--attributes and future directions.

PMID- 18810853
TI  - Fluorides and Caries Decline, Symposium in Orlando, Florida on March 9, 2006:
      introduction.

PMID- 18810854
TI  - Gestalt: radiology's aunt Minnie.

PMID- 18810855
TI  - End-of-life care in chronic obstructive pulmonary disease.

PMID- 18810856
TI  - Re: Gao Z, Rowe BH, Majaesic C, O'Hara C, Senthilselvan A. Prevalence of asthma
      and risk factors for asthma-like symptoms in Aboriginal and non-Aboriginal
      children in the northern territories of Canada. Can Respir J 2008; 15: 139-45.

PMID- 18810857
TI  - [New paradigm for treatment and prevention of osteoporosis].

PMID- 18810858
TI  - Source tracking of Escherichia coli O157:H7 and Salmonella contamination in the
      lairage environment at commercial U.S. beef processing plants and identification
      of an effective intervention.
AB  - Transportation from the feedlot and lairage at the processing plant have been
      identified as potential sources of Escherichia coli O157:H7 and Salmonella hide
      contamination. The objective of this study was to perform a comprehensive
      tracking analysis of E. coli O157:H7 and Salmonella associated with beef cattle
      from the feedlot through processing. Cattle (n = 581) were sampled in a feedlot,
      then transported in multiple lots to three commercial, fed beef processing plants
      in the United States, where they were sampled again. Samples were collected from
      the tractor trailers prior to loading cattle and from the lairage environment
      spaces prior to entry of the study cattle. Pathogen prevalence on cattle hides
      increased on every lot of cattle between exiting the feedlot and beginning
      processing. Prior to loading cattle, E. coli O157:H7 was found in 9 (64%) of 14
      tractor trailers. E. coli O157:H7 was detected in over 60% of the samples from
      each lairage environment area, while Salmonella was detected in over 70% of the
      samples from each lairage environment area. E. coli O157:H7 and Salmonella
      isolates (n = 3,645) were analyzed using pulsed-field gel electrophoresis. The
      results of the pulsed-field gel electrophoresis tracking indicate that the
      transfer of bacteria onto cattle hides that occurs in the lairage environments of
      U.S beef processing plants accounts for a larger proportion of the hide and
      carcass contamination than does the initial bacterial population found on the
      cattle exiting the feedlot. Finally, the results of this study indicate that hide
      wash cabinets are effective in removing contamination derived from the lairage
      environment.

PMID- 18810859
TI  - Associations between the presence and magnitude of Escherichia coli O157 in feces
      at harvest and contamination of preintervention beef carcasses.
AB  - To quantify associations at slaughter between Escherichia coli O157 carcass
      contamination, fecal-positive animals, and high-shedding animals within
      truckloads of finished cattle, we sampled up to 32 cattle from each of 50
      truckloads arriving at a commercial abattoir in the Midwest United States during
      a 5-week summer period. Carcass swab samples collected pre-evisceration and fecal
      samples collected postevisceration were matched within animals and analyzed for
      the presence of E. coli O157, using enrichment, immunomagnetic separation, and
      plating on selective media (IMS). In addition, a direct plating procedure was
      performed on feces to identify high-shedding animals. E. coli O157 was isolated
      from 39 (2.6%) of 1,503 carcass samples in 15 (30%) truckloads, and 127 (8.5%) of
      1,495 fecal samples in 37 (74%) truckloads. Fifty-five (3.7%) high-shedding
      animals were detected from 26 (52%) truckloads. Truckload high-shedder (Spearman
      rank-order correlation coefficient [r(s)] = 0.68), IMS-positive (r(s) = 0.48),
      and combined fecal (r(s) = 0.61) prevalence were significantly correlated with
      carcass prevalence. The probability of isolating E. coli O157 from a carcass was
      not significantly associated with the high-shedder or fecal IMS status of the
      animal from which the carcass was derived. However, the probability of carcass
      contamination was significantly associated with all truckload-level measures of
      fecal E. coli O157, particularly whether or not a high shedder was present within
      the truckload (odds ratio = 16.2; 95% confidence interval, 6.3-43.6). Our results
      suggest that high shedders within a truckload at slaughter could be a target for
      mitigation strategies to reduce the probability of preevisceration carcass
      contamination.

PMID- 18810860
TI  - Effects of using reduced volumes of nonselective enrichment medium in methods for
      the detection of Escherichia coli O157:H7 from raw beef.
AB  - Recent work from our laboratory revealed that tryptic soy broth (TSB) was a
      superior enrichment medium for use in test-and-hold Escherichia coli O157:H7
      methods at levels down to a ratio of three volumes of medium to one volume of
      sample. Lower ratios were examined for their effect on results obtained from
      culture isolation, the BAX E. coli O157:H7 MP assay, and the Assurance GDS E.
      coli O157:H7 assay. Ground beef and boneless beef trim were inoculated with a
      high level (170 CFU/65 g of ground beef and 43 CFU/65 g of trim) and a low level
      (17 CFU/65 g of ground beef and 4 CFU/65 g of trim) of E. coli O157:H7 and
      enriched in 3, 1, 0.5, and 0 volumes of TSB. The volume of TSB used did not
      affect E. coli O157:H7 detection by culture isolation, Assurance GDS detection in
      ground beef or trim, or the BAX MP assay detection in ground beef. However, BAX
      MP assay detection of E. coli O157:H7 in beef trim was 50, 42, and 33% positive
      when enrichment volumes of 0.5x, 1x, and 3x, respectively, were used. Optimum
      results with all methods were obtained using 1 volume of TSB. We concluded that
      detection test results can be considered valid as long as enrichment medium is
      used, even when it is less than the specified 3 or 10 volumes.

PMID- 18810861
TI  - Detection of virulence-associated genes in Escherichia coli O157 and non-O157
      isolates from beef cattle, humans, and chickens.
AB  - Food-producing animals can be reservoirs of pathogenic Escherichia coli strains
      that can induce diseases in animals or humans. Contamination of food by E. coli
      O157:H7 raises immediate concerns about public health, although it is not clear
      whether all E. coli O157 isolates of animal origin are equally harmful to humans.
      Inversely, the pathogenic potential of atypical E. coli O157 isolates and several
      non-O157 serotypes often is ignored. We used a DNA microarray capable of
      detecting a subset of 346 genes to compare the virulence-associated genes present
      in eight E. coli O157 isolates from human cases, 14 antibiotic-resistant and/or
      hypermutable E. coli O157 isolates from beef cattle, and four antibiotic
      resistant, sorbitol-negative, non-O157 E. coli isolates from healthy broiler
      chickens. Hybridization on arrays (HOA) revealed that O157 isolates from beef
      cattle and humans were genetically distinct, although they possessed most of the
      same subset of virulence genes. HOA allowed discrimination between hypermutable
      and antibiotic-resistant O157 isolates from beef cattle based on hybridization
      results for the stx2 and ycgG genes (hypermutable) or ymfL, stx1, stx2, and
      hlyE(avian) genes (resistant). However, the absence of hybridization to gene yfdR
      characterized human isolates. HOA also revealed that an atypical sorbitol
      fermenting bovine O157 isolate lacked some genes of the type 3 secretion system,
      plasmid pO157, and the stx1 and stx2 genes. This isolate had a particular
      pathotype (eaeA(beta) tir(alpha) espA(alpha) espB(alpha) espD(alpha)) not found
      in typical E. coli O157:H7. HOA revealed that some non-O157 E. coli isolates from
      healthy chickens carried genes responsible for salmochelin- and yersiniabactin
      mediated iron uptake generally associated with pathogenic strains.

PMID- 18810862
TI  - Longitudinal study of prevalence of Campylobacter jejuni and Campylobacter coli
      from turkeys and swine grown in close proximity.
AB  - Eastern North Carolina is a major contributor to both turkey and swine production
      in the United States. In this region, turkeys and swine are frequently grown in
      close proximity and by common growers. To further characterize colonization of
      turkeys and swine with Campylobacter in such a setting, we investigated the
      prevalence of thermophilic campylobacters in eight paired operations involving
      turkey farms in close proximity to finishing swine farms. All 15 surveyed flocks
      and 15 herds were Campylobacter positive at one or more sampling times.
      Campylobacter was isolated from 1,310 (87%) of the 1,512 turkey samples and 1,116
      (77%) of the 1,448 swine samples. Most (> 99%) campylobacters from swine samples
      were Campylobacter coli, found in 59 to 97% of the samples from the different
      herds. Both Campylobacterjejuni and C. coli were recovered from the turkey flocks
      (overall prevalences of 52 and 35%, respectively). Prevalence among flocks ranged
      from 31 to 86% for C. jejuni and 0 to 67% for C. coli, and both species were
      recovered from most flocks. Relative prevalence of C. coli was higher in young
      birds (brooders), whereas C. jejuni predominated in grow-out birds (P < 0.0001).
      The prevalence of C. coli in a swine herd was generally not a good predictor for
      prevalence of this species in the corresponding turkey flock. These findings
      indicate that even though turkeys and swine grown in proximity to each other were
      commonly colonized with thermophilic campylobacters, the relative prevalences of
      C. jejuni and C. coli appear to be host associated.

PMID- 18810863
TI  - Performance and intestinal coliform counts in weaned piglets fed a probiotic
      culture (Lactobacillus casei subsp. casei CECT 4043) or an antibiotic.
AB  - The production of biomass and antibacterial extracellular products by
      Lactobacillus casei subsp. casei CECT 4043 was followed in both batch and in
      realkalized fed-batch cultures. Enhanced concentrations of biomass and
      antibacterial extracellular products were obtained with the use of the latter
      fermentation technique in comparison with the batch mode. The culture obtained by
      fed-batch fermentation was mixed with skim milk and used to prepare a probiotic
      feed for weaned piglets. To test the effect of the potentially probiotic culture
      of L. casei on body weight gain, feed intake, feed conversion efficiency, and on
      fecal coliform counts of piglets, two groups of animals received either feed
      supplemented with the probiotic preparation or avilamycin for 28 days. The
      control group was fed nonsupplemented feed. At the end of the administration
      period (day 28), the groups receiving probiotic and avilamycin exhibited the
      highest average body weight gain values, although the mean feed intake and feed
      conversion efficiency values were not different among the groups (P > 0.05). For
      the entire experimental period (42 days), the control group exhibited the lowest
      feed intake value, the probiotic group exhibited the highest feed conversion
      efficiency value, and the antibiotic group exhibited the highest body weight gain
      (P < 0.05). Interestingly, no significant difference in body weight gain was
      observed between the probiotic and the control groups by day 42 (P > 0.05). Fecal
      coliform values decreased (although not significantly) by day 28 in the three
      groups. However, the mean counts returned to pretreatment levels by day 42 in all
      groups.

PMID- 18810864
TI  - Evaluating the growth of Listeria monocytogenes in refrigerated ready-to-eat
      frankfurters: influence of strain, temperature, packaging, lactate and diacetate,
      and background microflora.
AB  - This research was conducted to study the growth of Listeria monocytogenes
      inoculated on frankfurters stored at different conditions as a basis for a safety
      based consume by shelf life date label. Three L. monocytogenes strains were
      separately inoculated at 10 to 20 CFU/cm2 onto frankfurters that were previously
      formulated with or without high pressure and with or without added 2% potassium
      lactate (PL) and 0.2% sodium diacetate (SD). Inoculated frankfurters were air or
      vacuum packaged; stored at 4, 8, or 12 degrees C; and L. monocytogenes and
      psychrotrophic plate counts were determined for 90, 60, and 45 days,
      respectively, or until the stationary phase was reached. The data (log CFU per
      square centimeter versus time) were fitted using the Baranyi-Roberts model to
      determine maximum growth rates and lag-phase time. The maximum growth rates and
      the lag time under each growth condition were used to calculate the time to reach
      100-fold the initial Listeria population. In frankfurters lacking PL and SD, the
      count of all strains increased by 2 log after 18 to 50 days at 4 degrees C and 4
      to 13 days at 8 degrees C. The growth was inhibited at 4 and 8 degrees C in
      frankfurters containing PL and SD, but one ribotype was capable of growing, with
      the time to reach 100-fold the initial Listeria population ranging from 19 to 35
      days at 12 degrees C. In most cases, the time to reach 100-fold the initial
      Listeria population of L. monocytogenes was significantly longer in vacuum
      packaged frankfurters as compared with air-packaged samples. Inclusion of PL and
      SD also inhibited the growth of psychrotrophs, but at all temperatures the
      psychrotrophic plate counts were greater than 4 log CFU/cm2 at the end of the
      experiments. These results indicated that despite the use of antimicrobials,
      certain L. monocytogenes strains could be capable of growing under storage-abuse
      conditions. Growth kinetics data could be useful for establishing a shelf life
      date label protocol under different handling scenarios.

PMID- 18810865
TI  - Competitiveness and antibacterial potential of bacteriocin-producing starter
      cultures in different types of fermented sausages.
AB  - Application of bacteriocin-producing starter cultures of lactic acid bacteria in
      fermented sausage production contributes to food safety. This is sometimes
      hampered by limited efficacy in situ and by uncertainty about strain dependency
      and universal applicability for different sausage types. In the present study, a
      promising antilisterial-bacteriocin producer, Lactobacillus sakei CTC 494, was
      applied as a coculture in addition to commercial fermentative starters in
      different types of dry-fermented sausages. The strain was successful in both
      Belgian-type sausage and Italian salami that were artificially contaminated with
      about 3.5 log CFU g(-1) of Listeria monocytogenes. After completion of the
      production process, this led to listerial reductions of up to 1.4 and 0.6 log CFU
      g(-1), respectively. In a control sausage, containing only the commercial
      fermentative starter, the reduction was limited to 0.8 log CFU g(-1) for the
      Belgian-type recipe, where pH decreased from 5.9 to 4.9, whereas an increase of
      0.2 log CFU g(-1) was observed for Italian salami, in which the pH rose from 5.7
      to 5.9 after an initial decrease to pH 5.3. In a Cacciatore recipe inoculated
      with 5.5 log CFU g(-1) of L. monocytogenes and in the presence of L. sakei CTC
      494, there was a listerial reduction of 1.8 log CFU g(-1) at the end of the
      production process. This was superior to the effect obtained with the control
      sausage (0.8 log CFU g(-1)). Two commercial antilisterial cultures yielded
      reductions of 1.2 and 1.5 log CFU g(-1). Moreover, repetitive DNA sequence-based
      PCR fingerprinting demonstrated the competitive superiority of L. sakei CTC 494.

PMID- 18810866
TI  - Dynamic modeling of Listeria monocytogenes growth in pasteurized vanilla cream
      after postprocessing contamination.
AB  - A product-specific model was developed and validated under dynamic temperature
      conditions for predicting the growth of Listeria monocytogenes in pasteurized
      vanilla cream, a traditional milk-based product. Model performance was also
      compared with Growth Predictor and Sym'Previus predictive microbiology software
      packages. Commercially prepared vanilla cream samples were artificially
      inoculated with a five-strain cocktail of L. monocytogenes, with an initial
      concentration of 102 CFU g(-1), and stored at 3, 5, 10, and 15 degrees C for 36
      days. The growth kinetic parameters at each temperature were determined by the
      primary model of Baranyi and Roberts. The maximum specific growth rate (mu(max))
      was further modeled as a function of temperature by means of a square root-type
      model. The performance of the model in predicting the growth of the pathogen
      under dynamic temperature conditions was based on two different temperature
      scenarios with periodic changes from 4 to 15 degrees C. Growth prediction for
      dynamic temperature profiles was based on the square root model and the
      differential equations of the Baranyi and Roberts model, which were numerically
      integrated with respect to time. Model performance was based on the bias factor
      (B(f)), the accuracy factor (A(f)), the goodness-of-fit index (GoF), and the
      percent relative errors between observed and predicted growth. The product
      specific model developed in the present study accurately predicted the growth of
      L. monocytogenes under dynamic temperature conditions. The average values for the
      performance indices were 1.038, 1.068, and 0.397 for B(f), A(f), and GoF,
      respectively for both temperature scenarios assayed. Predictions from Growth
      Predictor and Sym'Previus overestimated pathogen growth. The average values of
      B(f), A(f), and GoF were 1.173, 1.174, 1.162, and 0.956, 1.115, 0.713 for
      [corrected] Growth Predictor and Sym'Previus, respectively.

PMID- 18810867
TI  - Modeling survival of Listeria monocytogenes in the traditional Greek soft cheese
      Katiki.
AB  - In the present work, survival of Listeria monocytogenes in the traditional Greek
      soft, spreadable cheese Katiki was studied throughout the shelf life of the
      product. Samples of finished cheese were inoculated with a cocktail of five L.
      monocytogenes strains (ca. 6 log CFU g(-1)) and stored at 5, 10, 15, and 20
      degrees C. Acid-stress adaptation or cross-protection to the same stress was also
      investigated by inoculation of acid-adapted cells in the product. The results
      showed that pathogen survival was biphasic. Various mathematical equations
      (Geeraerd, Cerf, Albert-Mafart, Whiting, Zwietering, and Baranyi models) were
      fitted to the experimental data. A thorough statistical analysis was performed to
      choose the best model. The Geeraerd model was finally selected, and the results
      revealed no acid tolerance acquisition (no significant differences, P > 0.05, in
      the survival rates of the non-acid-adapted and acid-adapted cells). Secondary
      modeling (second-order polynomial with a(0) = 0.8453, a(1) = -0.0743, and a(2) =
      0.0059) of the survival rate (of sensitive population), and other parameters that
      were similar at all temperatures (fraction of initial population in the major
      population = 99.98%, survival rate of resistant population = 0.10 day(-1), and
      initial population = 6.29 log CFU g(-1)), showed that survival of the pathogen
      was temperature dependent with bacterial cells surviving for a longer period of
      time at lower temperatures. Finally, the developed predictive model was
      successfully validated at two independent temperatures (12 and 17 degrees C).
      This study underlines the usefulness of predictive modeling as a tool for
      realistic estimation and control of L. monocytogenes risk in food products. Such
      data are also useful when conducting risk assessment studies.

PMID- 18810868
TI  - Efficacy of plant essential oils against foodborne pathogens and spoilage
      bacteria associated with ready-to-eat vegetables: antimicrobial and sensory
      screening.
AB  - The objectives of this study were to evaluate the antimicrobial activity of plant
      essential oils (EOs) against foodborne pathogens and key spoilage bacteria
      pertinent to ready-to-eat vegetables and to screen the selected EOs for sensory
      acceptability. The EOs basil, caraway, fennel, lemon balm, marjoram, nutmeg,
      oregano, parsley, rosemary, sage, and thyme were evaluated. The bacteria
      evaluated were Listeria spp., Staphylococcus aureus, Lactobacillus spp., Bacillus
      cereus, Salmonella, Enterobacter spp., Escherichia coli, and Pseudomonas spp.
      Quantitative antimicrobial analyses were performed using an absorbance-based
      microplate assay. Efficacy was compared using MIC, the half maximum inhibitory
      concentration, and the increase in lag phase. Generally, gram-positive bacteria
      were more sensitive to EOs than were gram-negative bacteria, and Listeria
      monocytogenes strains were among the most sensitive. Of the spoilage organisms,
      Pseudomonas spp. were the most resistant. Oregano and thyme EOs had the highest
      activity against all the tested bacteria. Marjoram and basil EOs had selectively
      high activity against B. cereus, Enterobacter aerogenes, E. coli, and Salmonella,
      and lemon balm and sage EOs had adequate activity against L. monocytogenes and S.
      aureus. Within bacterial species, EO efficacy was dependent on strain and in some
      cases the origin of the strain. On a carrot model product, basil, lemon balm,
      marjoram, oregano, and thyme EOs were deemed organoleptically acceptable, but
      only oregano and marjoram EOs were deemed acceptable for lettuce. Selected EOs
      may be useful as natural and safe additives for promoting the safety and quality
      of ready-to-eat vegetables.

PMID- 18810869
TI  - Characteristics of enterotoxin H-producing Staphylococcus aureus isolated from
      clinical cases and properties of the enterotoxin productivity.
AB  - Staphylococcal enterotoxin H (SEH) is predicted to be involved in staphylococcal
      food poisoning. To characterize SEH-producing Staphylococcus aureus isolates from
      staphylococcal food poisoning cases in Japan, we investigated the relationship
      between SEH production and coagulase serotype, which is an epidemiological
      marker, and compared the properties of SEH production with those of
      staphylococcal enterotoxins A (SEA) and B (SEB). SEH production was determined by
      a newly developed sandwich enzyme-linked immunosorbent assay. Eighty-six (59.7%)
      of 144 isolates from staphylococcal food poisoning cases produced SEH. Seventy
      one of the SEH-producing isolates simultaneously produced SEA, SEB, or both. All
      SEH-producing isolates belonged to coagulase type VII, which was the predominant
      type, representing 99 (68.8%) of 144 isolates. The amount of SEH produced in
      brain heart infusion was almost the same as the amount of SEA and approximately
      10-fold lower than that of SEB. SEH and SEA were produced mainly during the late
      exponential phase of growth, whereas SEB was produced mostly during the
      stationary phase. The production levels of SEH and SEA were gradually affected by
      decreases in water activity, but the production of SEB was greatly reduced under
      conditions of low water activity. These findings indicate that SEH-producing S.
      aureus isolates are of high prevalence in staphylococcal food poisoning cases.
      Given the unique epidemiological characteristic of these isolates, SEH and SEA
      probably are responsible for food poisoning.

PMID- 18810870
TI  - Enhanced inactivation of foodborne pathogenic and spoilage bacteria by FD&C Red
      no. 3 and other xanthene derivatives during ultrahigh pressure processing.
AB  - Variability among microorganisms in barotolerance has been demonstrated at genus,
      species, and strain levels. Identification of conditions and additives that
      enhance the efficacy of ultrahigh pressure (UHP) against important foodborne
      microorganisms is crucial for maximizing product safety and stability.
      Preliminary work indicated that FD&C Red No. 3 (Red 3), a xanthene derivative,
      was bactericidal and acted synergistically with UHP against Lactobacillus spp.
      The objective of this study was to determine the antimicrobial efficacy of Red 3
      and other xanthene derivatives, alone and combined with UHP, against spoilage and
      pathogenic bacteria in citrate-phosphate buffer (pH 7.0). Xanthene derivatives
      tested were fluorescein, Eosin Y, Erythrosin B, Phloxine B, Red 3, and Rose
      Bengal. Halogenated xanthene derivatives (10 ppm) were effective at reducing
      Listeria monocytogenes survivors but ineffective against Escherichia coli
      O157:H7. When combined with UHP (400 MPa, 3 min), the presence of derivatives
      enhanced inactivation. Because Red 3 was the only xanthene derivative to produce
      synergistic inactivation of both pathogens, further studies using this colorant
      were warranted. Efficacy of Red 3 against gram-positive bacteria (Lactobacillus
      plantarum and L. monocytogenes) was concentration dependent (1 to 10 ppm). E. coi
      O157: H7 strains were resistant to Red 3 concentrations up to 300 ppm. When Red 3
      was combined with UHP, the lethality against gram-positive and gram-negative
      bacteria was dose dependent, with synergy being significant for most strains at >
      or = 3 ppm. Additional gram-positive and gram-negative bacteria showed
      lethalities similar to those observed for L. plantarum or L. monocytogenes, and
      E. coli O157:H7, respectively. Red 3 is a potentially useful additive to enhance
      the safety and stability of UHP-treated food products.

PMID- 18810871
TI  - Detection of abrin in food using enzyme-linked immunosorbent assay and
      electrochemiluminescence technologies.
AB  - Abrin is a toxic ribosome-inactivating protein present in beans of Abrus
      precatorius, also known as rosary peas. The possibility that abrin could be used
      to adulterate food has made the development of assays for the detection of abrin
      a priority. Rabbit-derived polyclonal antibodies and mouse monoclonal antibodies
      were prepared against a mixture of abrin isozymes. The specificity and cross
      reactivity of the antibodies were evaluated against a challenge library of 40
      grains, nuts, legumes, and foods. An enzyme-linked immunosorbent assay (ELISA)
      and an electrochemiluminescence (ECL)-based assay were assembled and optimized.
      Polyclonal (capture) and polyclonal (detection) ELISAs, polyclonal and monoclonal
      ELISAs, and polyclonal and monoclonal ECL assays had limits of detection (LODs)
      of 0.1 to 0.5 ng/ml for abrin in buffer. The LOD for abrin dissolved into juices,
      dairy products, soda, chocolate drink, and condiments and analyzed with the ECL
      assay ranged from 0.1 to 0.5 ng/ml in the analytical sample. In contrast, the
      LODs for the ELISAs ranged from 0.5 to 10 ng/ml in the analytical sample.

PMID- 18810872
TI  - Toxicity and detection of ricin and abrin in beverages.
AB  - The oral and intraperitoneal (i.p.) toxicities to female BALB/c mice of ricin and
      abrin in phosphate-buffered saline (PBS), spring water, apple juice, and half-and
      half (only oral) were examined after brief (2 h) and prolonged (11 to 13 days)
      storage. The ricin and abrin samples prepared in PBS had oral toxicities
      consistent with those previous studies, indicating oral and i.p. 50% lethal doses
      of > 1 mg/kg of body weight and between 2 and 20 microg/kg of body weight,
      respectively. The toxicities of ricin and abrin in PBS were greater than those in
      apple juice and water. The oral toxicity of ricin and abrin in half-and-half
      appeared comparable to or less than that observed for the toxins in water. Spiked
      samples stored for a maximum of 11 days (13 for the abrin samples) at 4 degrees C
      induced similar numbers of fatalities as did samples stored for only 2 h. Enzyme
      linked immunosorbent assays of the samples administered by i.p. injection
      indicated a decrease in detectable toxin at 0.5 microg/ml.

PMID- 18810873
TI  - Assessment of the colorimetric and fluorometric assays for alkaline phosphatase
      activity in cow's, goat's, and sheep's milk.
AB  - Raw milk is a well-established vehicle for the carriage of human pathogens, and
      many regulatory bodies have consequently mandated compulsory pasteurization as a
      food safety intervention. The residual activity of alkaline phosphatase (ALP) has
      historically been used to verify the adequacy of pasteurization of cow's milk.
      However, there is uncertainty on how the current ALP standards and methods of
      analysis can be applied to sheep's and goat's milk, which naturally contain
      different levels of the enzyme than that found in cow's milk. The official ALP
      methods applied in Canada (colorimetric assay; MFO-3) and in the United States
      (Fluorophos) were assessed for their ability to detect enzyme activity in raw and
      pasteurized milk derived from cows, sheep, and goats. The detection limit and the
      limit of quantitation were 0.8 and 2.02 microg/ml phenol, respectively, for the
      MFO-3 method and 43 and 85 mU/liter, respectively, for the Fluorophos method. The
      average ALP levels in raw goat's, cow's, and sheep's milk were 165, 1,562, and
      3,512 microg/ml phenol, respectively. Raw milk detection limits, which correspond
      to raw milk phosphatase levels, were 0.051, 0.485, and 0.023% in cow's, goat's,
      and sheep's milk, respectively, for the MFO-3 method and 0.007, 0.070, and
      0.004%, respectively, for the Fluorophos method. Although both methods can be
      used for ALP determination in cow's, goat's, and sheep's milk, the Fluorophos
      assay was superior to the colorimetric MFO-3 method based on sensitivity and time
      required to complete the analysis.

PMID- 18810874
TI  - Efficiency of whole and skimmed powdered milk for trapping volatile compounds
      released from plastic containers in high-temperature applications.
AB  - Plastic food containers used for high-temperature applications are not completely
      inert, and potentially harmful chemicals may be transferred to foodstuffs when
      such containers are heated. The aim of this work was to investigate the role of
      food fat content on the efficiency of trapping volatile organic compounds from
      heated plastic packaging. Relatively simple food matrices such as powdered
      skimmed and whole milk were evaluated with respect to their retention of several
      selected migrants: toluene, 1-octene, ethylbenzene, o-, m-, and p-xylene,
      styrene, and 1,4-dichlorobenzene released from containers made of polypropylene
      (random and copolymer), polycarbonate, and styrene-acrylonitrile copolymer, which
      are all commonly used in high-temperature applications. The analytical method
      (purge and trap gas chromatography and mass spectrometry) was optimized for each
      matrix. The developed procedure had detection limits of 0.01 to 1.2 ng, depending
      on the analyte and sample matrix, and both reproducibility and repeatability
      (expressed as relative standard deviation) were below 15%. This method was
      applied to the different plastic materials. The concentrations of the volatile
      compounds in both matrices were well below the established specific migration
      limits. Temperature and fat content of powdered milk were the most influential
      variables in mass transfer processes. These values were compared with those
      obtained with either Tenax TA (alternative test medium for fatty food simulants)
      or Porapak Q (another widely used sorbent). Similar results were found in skimmed
      powdered milk and Tenax TA, but significant differences were observed for whole
      powdered milk.

PMID- 18810875
TI  - Domestic refrigeration practices with emphasis on hygiene: analysis of a survey
      and consumer recommendations.
AB  - A Web-enabled survey was conducted to improve knowledge of home refrigeration
      practices of French consumers (n = 809), with an emphasis on hygiene, and this
      information was used to establish recommendations. The survey targeted a
      convenience sample of working people. Analysis of the survey responses revealed
      that efforts should be directed toward improvement of microbiological control
      measures. Only 37% of respondents made sure the temperature in their refrigerator
      was 4 degrees C or below. Only 37% of respondents reported that they
      systematically wrapped food. Sponges, known to be frequently highly contaminated,
      were used by 89% of the respondents to clean their refrigerator, which indicates
      the need to recommend disinfection of sponges before they are used for cleaning.
      Twenty-seven percent of respondents used sodium hypochlorite (bleach), but it was
      applied without previous cleaning (21% of the users) or in the commercial
      concentrated form (7% of the users). The permanent presence of water condensation
      on the shelves was noted by 2% of respondents, suggesting imperfect closure of
      the door, with a consequence of higher energy consumption and water available for
      microbial circulation and growth. Thus, an important recommendation is to check
      the door gaskets and to ensure the tight closure of the door. Seventy percent of
      the respondents declared that they never put warm or hot food in the
      refrigerator. However, many people, when orally questioned, acknowledged that
      they leave dishes at ambient temperature overnight before putting them in the
      refrigerator. It therefore is essential to recommend that perishable food not be
      left for more than 2 h at ambient temperature.

PMID- 18810876
TI  - Multiplication of Salmonella enteritidis on the yolk membrane and penetration to
      the yolk contents at 30 degrees C in an in vitro egg contamination model.
AB  - Refrigeration to limit bacterial multiplication is a critical aspect of efforts
      to control the transmission of Salmonella enterica serovar Enteritidis (SE) to
      consumers of contaminated eggs. Although the nutrient-rich yolk interior is an
      uncommon location for SE contamination in freshly laid, naturally contaminated
      eggs, migration across the vitelline membrane could lead to rapid bacterial
      multiplication even when the initial site of deposition is outside the yolk.
      Multiplication on the yolk membrane (before, or in addition to, multiplication
      within the yolk contents) could be another source of increased risk to consumers.
      The present study used an in vitro egg contamination model to compare the
      abilities of four strains of SE to either multiply in association with the yolk
      membrane or migrate through that membrane to reach the yolk contents during 36 h
      of incubation at 30 degrees C. After inoculation onto the exterior surface of
      intact, whole yolks, all four SE strains penetrated the vitelline membrane to
      reach the yolk contents (at an overall frequency of 11.5%) after 12 h of
      incubation. The mean log concentration of SE was significantly higher in whole
      yolks (including yolk membranes) than in yolk contents at both 12 h (0.818 versus
      0.167 CFU/ ml) and 36 h (2.767 versus 1.402 CFU/ml) of incubation. These results
      demonstrate that SE multiplication on the vitelline membrane may both precede and
      exceed multiplication resulting from penetration into the yolk contents during
      the first 36 h of unrefrigerated storage, reinforcing the importance of rapid
      refrigeration for protecting consumers from egg-transmitted illness.

PMID- 18810877
TI  - Tracing the contamination origin of coliform bacteria in two small food
      processing factories.
AB  - The objective of this study was to trace contamination sources of coliform
      bacteria by comparing the types of coliforms between food samples and the
      processing environments in two small food-processing factories (factories A and
      B). Fermentation tests of five sugars enabled the successful classification of 16
      representative type strains into eight distinct groups. The grouping procedure
      was then applied to comparison of the coliform flora between food products and
      various locations in their processing environments. The consistency between each
      food and the tested locations was evaluated using the Jaccard index. The air
      conditioner and refrigeration room floor in factory A showed an index of 1.00,
      while the shaping machine in factory B showed an index of 0.98, indicating that
      these locations could be contamination sources. The validity of our results was
      confirmed by randomly amplified polymorphic DNA, which showed 100% matched
      profiles between the air conditioner and the food in factory A, and highly
      matched profiles between the machine and the food in factory B. This method for
      comparing the coliform flora between food and environments has the potential to
      be a reliable tracing tool for various food industries.

PMID- 18810878
TI  - Modeling the physiological state of the inoculum and CO2 atmosphere on the lag
      phase and growth rate of Listeria monocytogenes.
AB  - In previous studies, the growth of L. monocytogenes has been modeled under
      different CO2 headspace concentrations; however, the inoculum cells were always
      in the stationary phase. In this study, the growth of L. monocytogenes under
      different CO2 concentrations as affected by the physiological state of the cells
      was investigated. Exponential-growth-phase, stationary-phase, dried, and starved
      cells were prepared and inoculated at 5 degrees C into brain heart infusion
      broths that had been preequilibrated under atmospheres of 0, 20, 40, 60, or 80%
      CO2 (the balance was N2). Lag-phase duration times (LDTs) and exponential growth
      rates were determined by enumerating cells at appropriate time intervals and by
      fitting the data to a three-phase linear function that has a lag period before
      the initiation of exponential growth. Longer LDTs were observed as the CO2
      concentration increased, with no growth observed at 80% CO2. For example, the
      LDTs for exponential-phase, stationary-phase, starved, and dried cells were 2.21,
      8.27, 9.17, and 9.67 days, respectively, under the 40% CO2 atmosphere. In
      general, exponential-growth-phase cells had the shortest LDT followed by starved
      cells and stationary-phase cells. Dried cells had the longest LDT. Exponential
      growth rates decreased as the CO2 concentrations increased. Once exponential
      growth was attained, no retained differences among the various initial
      physiological states of the cells for any of the atmospheres were observed in the
      exponential growth rates. The exponential growth rates under 0, 20, 40, 60, and
      80% CO2 averaged 0.39, 0.37, 0.23, 0.23, and 0.0 log CFU/day, respectively.
      Dimensionless factors were calculated that describe the inhibitory action of CO2
      on the LDTs and exponential growth rates for the various physiological states.

PMID- 18810879
TI  - Microbial populations on hides of grazing steers in a forage-based production
      system in Uruguay.
AB  - The objective of the study was to evaluate the microbiological status of hides of
      grazing steers in a typical forage-based system in Uruguay. The study was
      conducted on a single farm with samples taken on 3 days during the spring of
      2007. Four anatomical hide sites (perineum area, flank, back, and shoulder) of 10
      steers were individually swabbed each sampling day at the farm environment (n =
      120). Each sample was analyzed by the Laboratorio Tecnologico del Uruguay for
      aerobic plate counts (APC), total coliform counts (TCC), and Escherichia coli
      counts (ECC). Mean log values for APC, TCC, and ECC on external animal hide
      surfaces, across all sampling sites, were 5.52, 1.89, and 1.70 log CFU/cm2,
      respectively. There were no significant differences among bacterial counts from
      the four hide surface locations. Mean log values for APC, TCC, and ECC were 1.49,
      1.15, and 1.12 log CFU/cm2 lower, respectively, on sampling day 2 than on
      sampling day 3. Microbial populations on hides of grazing steers are highly
      variable and dependent on climatic and environmental conditions. To our knowledge
      this is the first study published evaluating the hygienic conditions of grazing
      livestock operations in Uruguay and their potential implications on the red meat
      chain.

PMID- 18810880
TI  - Effect of a reactive oxygen species-generating system for control of airborne
      microorganisms in a meat-processing environment.
AB  - The effectiveness of reactive oxygen species (ROS)-generating AirOcare equipment
      on the reduction of airborne bacteria in a meat-processing environment was
      determined. Serratia marcescens and lactic acid bacteria (Lactococcus lactis
      subsp. lactis and Lactobacillus plantarum) were used to artificially contaminate
      the air via a six-jet Collison nebulizer. Air in the meat-processing room was
      sampled immediately after aerosol generation and at various predetermined times
      at multiple locations by using a Staplex 6 stage air sampler. Approximately a 4
      log reduction of the aerial S. marcescens population was observed within 2 h of
      treatment (P < 0.05) compared to a 1-log reduction in control samples. The S.
      marcescens populations reduced further by approximately 4.5 log after 24 h of
      exposure to ROS treatment. Approximately 3-log CFU/m3 reductions in lactic acid
      bacteria were observed following 2-h ROS exposure. Further ROS exposure reduced
      lactic acid bacteria in the air; however, the difference in their survival after
      24 h of exposure was not significantly different from that observed with the
      control treatment. S. marcescens bacteria were more sensitive to ROS treatment
      than the lactic acid bacteria. These findings reveal that ROS treatment using the
      AirOcare unit significantly reduces airborne S. marcescens and lactic acid
      bacteria in meat-processing environments within 2 h.

PMID- 18810881
TI  - Antibacterial activity of xanthorrhizol isolated from Curcuma xanthorrhiza Roxb.
      against foodborne pathogens.
AB  - Xanthorrhizol, isolated from the ethanol extract of Curcuma xanthorrhiza Roxb.,
      is a sesquiterpene compound with a molecular weight of 218. The aim of this study
      was to investigate the antibacterial activity of xanthorrhizol against foodborne
      pathogens. The antibacterial activity of xanthorrhizol was measured in terms of
      the MIC and the MBC. MICs and MBCs of xanthorrhizol against Bacillus cereus,
      Clostridium perfringens, Listeria monocytogenes, Staphylococcus aureus,
      Salmonella Typhimurium, and Vibrio parahaemolyticus were 8, 16, 8, 8, 16, 8
      microg/ml and 16, 32, 16, 16, 16, 16 microg/ml, respectively. The bactericidal
      study, as determined by the viable cell count method, revealed that xanthorrhizol
      treatment at 4 x MIC reduced viable cells by at least 6 to 8 log for all six
      foodborne pathogens in 4 h. Xanthorrhizol maintained its antibacterial activity
      after thermal treatments (121 degrees C, 15 min) under various pH ranges (pH 3.0,
      7.0, and 11.0). These results strongly suggest that xanthorrhizol, conferring
      strong antibacterial activity with thermal and pH stability, can be effectively
      used as a natural preservative to prevent the growth of foodborne pathogens.

PMID- 18810882
TI  - Detection of deoxynivalenol contamination in wheat products in Thailand.
AB  - A total of ninety samples in three kinds of wheat products (30 noodle, 30 bread,
      and 30 cereal samples) were collected from the supermarkets in Bangkok, Thailand,
      from February to April 2007. The occurrence of deoxynivalenol (DON) contamination
      in wheat products was investigated using high-performance liquid chromatography
      equipped with a UV light detector. The extraction method was performed using a
      multifunctional cleanup column. The limit of quantification was 0.10 microg x g(
      1) from the range obtained in a linear calibration. The survey found almost 94%
      of the DON-contaminated samples below 1 microg x g(-1), which corresponds to the
      U.S. Food and Drug Administration advisory level. DON was detected in 18.9% (17
      of 90) of all samples, in 6.67% (2 of 30) and 16.67% (5 of 30) of noodle and
      bread samples at levels from 0.17 to 0.35 and 0.14 to 1.13 microg x g(-1),
      respectively, while it was in 33.33% (10 of 30) of cereal samples at levels from
      0.13 to 0.39 microg x g(-1). The results suggest that the exposure to DON from
      the consumption of wheat products, especially noodles, bread, and cereal, is at a
      very low risk level.

PMID- 18810883
TI  - Electrolyzed water and its application in the food industry.
AB  - Electrolyzed water (EW) is gaining popularity as a sanitizer in the food
      industries of many countries. By electrolysis, a dilute sodium chloride solution
      dissociates into acidic electrolyzed water (AEW), which has a pH of 2 to 3, an
      oxidation-reduction potential of >1,100 mV, and an active chlorine content of 10
      to 90 ppm, and basic electrolyzed water (BEW), which has a pH of 10 to 13 and an
      oxidation-reduction potential of -800 to -900 mV. Vegetative cells of various
      bacteria in suspension were generally reduced by > 6.0 log CFU/ml when AEW was
      used. However, AEW is a less effective bactericide on utensils, surfaces, and
      food products because of factors such as surface type and the presence of organic
      matter. Reductions of bacteria on surfaces and utensils or vegetables and fruits
      mainly ranged from about 2.0 to 6.0 or 1.0 to 3.5 orders of magnitude,
      respectively. Higher reductions were obtained for tomatoes. For chicken
      carcasses, pork, and fish, reductions ranged from about 0.8 to 3.0, 1.0 to 1.8,
      and 0.4 to 2.8 orders of magnitude, respectively. Considerable reductions were
      achieved with AEW on eggs. On some food commodities, treatment with BEW followed
      by AEW produced higher reductions than did treatment with AEW only. EW technology
      deserves consideration when discussing industrial sanitization of equipment and
      decontamination of food products. Nevertheless, decontamination treatments for
      food products always should be considered part of an integral food safety system.
      Such treatments cannot replace strict adherence to good manufacturing and hygiene
      practices.

PMID- 18810884
TI  - Differences in mortality between rural and urban areas in England and Wales, 2002
      04.
AB  - This article examines differences in mortality between rural and urban areas in
      England and Wales in the years 2002-04 using the Rural and Urban Area
      Classification 2004. The analysis includes adjustment using the Index of Multiple
      Deprivation 2004 and Welsh Index of Multiple Deprivation 2005 to investigate
      whether mortality differences between rural and urban areas could be explained by
      differences in the distribution of deprivation.

PMID- 18810885
TI  - Geographical variations in deaths related to drug misuse in England and Wales,
      1993-2006.
AB  - Drug misuse is a significant public health issue in England and Wales. This
      article examines geographical variations in drug misuse mortality in England and
      Wales over the period 1993 t 2006. Geographical variations in deaths related to
      drug misuse have generally persisted over this period, one of substantial change
      in these deaths (with a peak in 2001 and numbers in 2006 being almost double
      those in 1993), although there were some significant changes to the regional
      level pattern. The regions with the highest mortality rates aggregated over the
      whole time period were the North West, Yorkshire and The Humber, and London,
      although by 2004/06 the rate in London was among the lowest and the rate in the
      North East was higher than the North West. Three Drug Action Teams (DATs),
      Brighton and Hove, Blackpool, and Camden, consistently had the highest drug
      misuse mortality rates. Urban areas tended to have the highest rates, but the
      rate in the most sparsely populated areas was similar to those of towns. The
      mortality rate in the most deprived parts of England and Wales was five times the
      rate in the least deprived areas. Areas with low rates were generally large,
      mostly rural areas, as well as areas in outer London and the south east of
      England.

PMID- 18810886
TI  - Birthweight and gestational age by ethnic group, England and Wales 2005:
      introducing new data on births.
AB  - Low birthweight babies and babies born preterm are at increased risk of morbidity
      and mortality in the first year of life, as well as in the longer-term. Since
      information on ethnic group is not recorded at birth registration in England and
      Wales, it has not been possible to produce routine statistics on birthweight or
      gestational age by ethnic group. A new system, introduced in 2002, for allocating
      NHS numbers at birth (NN4B) provided the opportunity to obtain ethnic group
      information. The NN4B record includes information on the ethnic group of the baby
      classified according to the 2001 Census categories. This paper presents the first
      analyses of ethnic differences in birthweight and gestational age at birth for
      England and Wales as a whole. Utilising NN4B records linked with birth
      registration records for all births occurring in England and Wales in 2005,
      birthweight and gestational age distributions, including the percentages low
      birthweight and preterm, are compared between ethnic groups. The paper also
      examines how parental socio-demographic circumstances vary by ethnic group.

PMID- 18810887
TI  - Deaths involving MRSA: England and Wales, 200-07.

PMID- 18810888
TI  - Deaths involving Clostridium difficile; England and Wales, 2003-07.

PMID- 18810889
TI  - Unexplained deaths in infancy, 2006.

PMID- 18810890
TI  - Deaths related to drug poisoning in England and Wales, 2003-07.

PMID- 18810891
TI  - Death registrations in England and Wales, 2007, causes.

PMID- 18810892
TI  - Infant and perinatal mortality 2007: health areas, England and Wales.

PMID- 18810893
TI  - Hunting for a solution.

PMID- 18810894
TI  - Developing researchers.

PMID- 18810896
TI  - Time for a reality check.

PMID- 18810895
TI  - Market forces.

PMID- 18810897
TI  - Modern matrons: reviewing the role.

PMID- 18810898
TI  - The intelligent workforce.

PMID- 18810899
TI  - A re-examination of cultural safety: a national imperative.

PMID- 18810900
TI  - Te Kapunga Putohe (the restless hands): a Maori centred nursing practice model.
AB  - Maori are often confronted with nursing practices and services that are at odds
      with their traditionally wholistic and spiritually based worldview. Keeping Maori
      clients the central focus of nursing practice can be challenging for nurses but
      is one way they can increase their efficacy when working with Maori. However, in
      the nursing literature there is an absence of models to guide Maori centred
      nursing practice, that is, models constructed within a Maori cultural context. Te
      Kapunga Putohe (the restless hands) is a Maori centred nursing practice model
      that uses the hands to illustrate how Maori knowledge and the knowledge of nurses
      can be incorporated into the health experiences of Maori clients. This paper
      explains how nurses who possess knowledge of Te Ao Maori can use Te Kapunga
      Putohe (the restless hands) to work with Maori in a culturally appropriate and
      acceptable way to improve health outcomes.

PMID- 18810901
TI  - Patients' experiences of interpersonal relationships during first time acute
      hospitalisation.
AB  - This article examines the role of interpersonal relationships on patients'
      experiences during first time acute hospitalisation. It is developed from a wider
      study undertaken in 2000 in which patients' overall experiences were explored. A
      qualitative methodology was used with data collected by means of semi-structured
      interviews and personal stories. Twelve participants were involved, seven females
      and five males of varying ages, all first time acute medical and surgical
      admissions. Findings suggest that supportive interpersonal relationships reduce
      patient vulnerability and that nurses play a key role in the development and
      maintenance of these relationships.

PMID- 18810902
TI  - Maori women's views on smoking cessation initiatives.
AB  - Smoking is particularly prevalent among Maori women over the age of 15 years and
      remains a concern despite anti-smoking campaigns. This raises questions about the
      effectiveness of current smoking cessation initiatives as mainstream tobacco
      control programmes have not benefited Maori to the same extent as non-Maori.
      Limited research is available on the effectiveness of smoking cessation
      initiatives for Maori. In this descriptive qualitative study five Maori women who
      had ceased smoking were interviewed about such initiatives and what was more
      likely to influence Maori women to quit. A focus group was used to discuss
      smoking cessation initiatives and the data were thematically analysed using
      Boyatzis' (1998) approach. Two themes were identified: (a) Transmission of Whanau
      (immediate and extended family) Values that includes the sub-categories whanau
      experiences, being mothers, and role models; and (b) Factors Crucial in
      Influencing Change that includes the sub-categories choices and exercising own
      will, a positive perception of self and a Maori approach. The findings provide
      insight for nurses into Maori women's perspectives. These highlight the
      importance of whanau and supportive relationships, and can be used to inform
      strategies to assist Maori women in smoking cessation.

PMID- 18810903
TI  - Nurses' views of family nursing in community contexts: an exploratory study.
AB  - In their day to day practice nurses interact with 'family' as a whole in a
      variety of community locations. Public health, Practice, District, Well child
      health and Rural nurses participated in a qualitative study in which four focus
      groups were used to explore the ways in which each nurse integrated 'family' into
      their practice. Thematic analysis of the data revealed four related themes: the
      labyrinth of family nursing, relational webs, personal and professional knowing,
      and contextual determinants. It was found that 'family' was integrated into
      participants' community practice in a "narrative, dialogical, relational and
      contextual" manner (Doane Hartrick, 2002, p. 623). Each family/nurse interaction
      had its own story exemplifying the contextual complexity and uncertainty, while
      at the same time showing the deep satisfaction inherent in working with families.
      Paramount in this practice was dialogue and building relationships, not only with
      families, but also with colleagues, health and other professionals. While it is
      apparent a family/family health nursing role has yet to be established, the
      possibilities of such a role have been recognised in this study. Yet considerable
      work still remains to be done before this nursing role is seen as an imperative
      in improving family health and wellbeing.

PMID- 18810904
TI  - Jacobs, S., & Boddy, J. (2008). The genesis of advanced nursing practice in New
      Zealand: policy, politics and education, Nursing Praxis in New Zealand, 24(1), 11
      22.

PMID- 18810905
TI  - Ethics are moral, but morality is not ethics.

PMID- 18810906
TI  - FDA new drug approvals in 2007.

PMID- 18810907
TI  - Dental study clubs and mentorship.
AB  - Dentistry can be a very difficult profession in many ways, whether it's running a
      business in private practice, dealing with administrative and political
      aspirations in a school, or dealing with employees and the general public.
      Deciding on a type of continuing dental education can be a stressful experience
      as well. I belong to both a cast gold and a gold foil operating study club and
      mentor two other cast gold clubs. The experiences have been life-changing in some
      ways and have expanded my knowledge base about operative dentistry to a great
      degree. My clinical skills have improved dramatically and most importantly have
      been transferred to all aspects of my clinical dentistry practice. Joining or
      forming an operating study club with an experienced mentor is the most effective
      way to learn and improve a certain clinical skill and to reap the other benefits
      described above. It can be especially beneficial for a younger dentist to learn
      at a high level early in his or her career. I welcome any inquires concerning
      forming or joining a study club. Additional information regarding operating study
      clubs is available through the Academy of Richard V. Tucker Cast Gold Study Clubs
      (www.rvtucker.org), the Academy of Operative Dentistry
      (www.operativedentistry.com), and the American Academy of Gold Foil Operators
      (www.aagfo.com).

PMID- 18810908
TI  - Handpieces--air vs. electric.

PMID- 18810909
TI  - Replacement of congenitally missing lateral incisors with implant crowns.
AB  - Esthetic adolescent dental treatment has become a staple of the restorative
      office. The combined interdisciplinary efforts of the orthodontist, oral surgeon,
      and restorative dentist were necessary to achieve an esthetic and functionally
      successful result. Implant placement and restoration is a preferred solution for
      the replacement of missing teeth in any age group but is particularly beneficial
      for younger patients.

PMID- 18810910
TI  - Bioterrorism update--information for the dentist.
AB  - The United States was awakened to the perils of bioterrorism in October 2001 with
      the news that letters laced with anthrax had been mailed to the media and select
      politicians. At that time, it became evident that a widescale attack using a
      bioweapon of mass destruction could rapidly overwhelm the health care system.
      Dentists could make a tremendous contribution to the response of such an attack
      by gaining an understanding of the bioweapons that could be used, as well as the
      symptoms of their diseases and therapies for treatment. This article gives a
      general overview of the biological agents that terrorists are most likely to use
      and provides the dentist with information about how to contribute to an effective
      response in the event of such an attack.

PMID- 18810911
TI  - A systematic approach for removable partial denture design.
AB  - Implants are becoming increasingly popular as a means of restoring edentulous
      spaces. However, many patients still cannot afford implants or do not have enough
      bone to support them. For these patients, removable partial dentures are an
      option for restoring function to their dentition. This article presents a way of
      considering removable partial denture design without becoming overwhelmed and
      frustrated with the process. Retention, support, and stability are discussed.

PMID- 18810912
TI  - Linguoaxial wall and cervicoincisal dimension of anterior crown preparation:
      effect on retention.
AB  - This study sought to evaluate the effect of the linguoaxial wall, a lingual
      auxiliary groove, and the cervicoincisal dimension of the anterior tooth
      preparation on retention. A simulated maxillary central incisor was prepared
      following "ideal" guidelines. The linguoaxial wall of these preparations was
      modified and the samples were divided into three groups: preparations with a
      linguoaxial wall (Group 1), preparations with a linguoaxial wall and groove
      (Group 2), and preparations with no linguoaxial wall (Group 3). Ten metal dies
      and crowns were fabricated from each preparation group. A universal testing
      machine subjected cemented crowns to force along the long axis of the dies and
      load-to-dislodgement was measured. All preparations were shortened by 3.0 mm and
      crowns for the reduced-height groups were fabricated, cemented, and subjected to
      similar force. The preparations with the groove produced higher mean retention
      than the other groups. Among the reduced-height groups, the preparations with the
      groove also produced higher mean retention than the other groups. There were no
      differences in mean retention for the short and long preparation heights of each
      group.

PMID- 18810913
TI  - Ethical decision-making for multiple prescription dentistry.
AB  - Technology provides a selection of treatment choices for dental problems. Dental
      ethics must be applied to the development of a treatment plan and the selection
      of methods. Treatment options should consider the patient's circumstances and
      desires as well as the dentist's decision as it relates to best practices in
      dentistry. This article presents four case studies that illustrate the process of
      ethical decision-making for the appropriate treatment.

PMID- 18810914
TI  - Oral human papillomavirus lesion identified using VELscope instrumentation: case
      report.
AB  - The role of oral human papillomavirus (HPV) in the incidence of oral carcinoma
      has increased among traditional non-risk patients under the age 40. This case
      study describes how a squamous papilloma (attributed to the HPV) was discovered
      using the VELscope oral screening device. Photographs of the lesion that might
      help dentists to identify these areas, using both white light and fluorescence
      visualization with VELscope, are included.

PMID- 18810915
TI  - Technique for treatment of dens in dente.
AB  - This article describes a case involving a maxillary lateral incisor with dens in
      dente and how it was treated with a procedure that differs from standard
      endodontic treatment.

PMID- 18810916
TI  - Glandular odontogenic cyst of the mandible: from incidental radiographic
      discovery to prosthetic reconstruction.
AB  - A large multilocular radiolucent lesion involving the anterior mandible was noted
      incidentally in a 44-year-old woman who sought routine dental treatment. An
      incisional biopsy revealed that this lesion represented an uncommon developmental
      odontogenic cyst known as a glandular odontogenic cyst. The lesion was removed
      surgically, followed by reconstruction with a right anterior iliac crest bone
      graft. This article reviews the radiographic, clinical, and histopathologic
      appearance of this rare odontogenic cyst, as well as the surgical management and
      the patient's subsequent prosthetic rehabilitation.

PMID- 18810917
TI  - Florid cemento-osseous dysplasia mimicking multiple periapical pathology--an
      endodontic dilemma.
AB  - A case of florid cemento-osseous dysplasia (COD) mimicking periapical pathology
      is presented. The fact that the patient's lesion failed to resolve three years
      after root canal therapy, in addition to the presence of a mixed radiolucency
      with discreet radiopacities, mandated a biopsy which (along with radiographic co
      relation) confirmed the diagnosis of cemento-osseous dysplasia. This case report
      illustrates the point that periapical radiolucencies may represent benign fibro
      osseous lesions that may be overlooked or result in unnecessary endodontic
      treatment.

PMID- 18810918
TI  - Prevention and management of trigeminal herpes zoster and postherpetic neuralgia.
AB  - Herpes zoster (HZ, also known as shingles) is caused by the reactivation of a
      dormant varicella zoster virus and can be a source of significant morbidity. Oral
      manifestations can include vesicular eruptions of the mucosa, osteonecrosis with
      tooth loss, and postherpetic neuralgia (PHN). This article discusses treatment
      for trigeminal nerve involvement with herpes zoster, as well as for the painful
      syndrome PHN.

PMID- 18810919
TI  - Effect of two axial wall height preparations on the retentive properties of full
      crowns using three different cements.
AB  - This study evaluated how different tooth preparation heights and luting cements
      affected the retention of metallic full crowns. Tooth preparations were made on
      60 extracted maxillary premolars with occluso-cervical heights of 4.0 or 5.0 mm.
      The nickel chromium (NiCr) metallic crowns in each group were subdivided randomly
      into three groups (n = 10); the samples in each group were cemented with either a
      self-adhesive resin cement, a conventional resin cement, or a zinc phosphate
      cement. Cementation was performed by applying 5.0 kg pressure in 50% relative
      humidity. Specimens were stored in 100% humidity at 37 degrees C for seven days,
      at which time they were subjected to a vertical tensile test with a universal
      testing machine at 0.5 mm/min. Data (Kgf) were analyzed by two-way ANOVA and
      Tukey's multiple comparisons tests (alpha = 0.01). There was a significant
      difference in mean force in the height preparations (P < 0.001) and in tensile
      strength (P < 0.001) among the resin cements. Regardless of the cement used, 5.0
      mm high preparations showed significantly higher mean forces than the 4.0 mm high
      preparations. The self-adhesive resin cement showed significantly higher mean
      tensile strength than the conventional resin cement; the zinc phosphate cement
      displayed the lowest retention values. The self-adhesive resin cement displayed
      retention rates twice that of the zinc phosphate cement.

PMID- 18810920
TI  - Endosseous implants versus nonsurgical root canal therapy: a systematic review of
      the literature.
AB  - For this article, the authors identified and reviewed the current literature,
      addressing two treatment options for endodontically involved teeth: root canal
      therapy and restoration versus extraction and the placement of a dental implant.
      The literature was evaluated as a basis for making treatment decisions. PubMed
      was queried for all studies that compared nonsurgical root canal therapy (NSRCT)
      and restoration with the extraction of teeth and placement of a dental implant.
      This search was supplemented by searching the bibliographies of these studies to
      ensure that all relevant studies were included. A total of 38 studies were found
      that directly compared NSRCT and restoration with extraction and placement of a
      dental implant. The literature is discussed in terms of outcomes for both
      treatment options, considerations in treatment plan decision-making, or the
      opinions of the authors.

PMID- 18810921
TI  - Periapical radiolucency of the anterior mandible. Simple bone cyst.

PMID- 18810922
TI  - Pericoronal radiolucency with radiopacities of posterior mandible. Ameloblastic
      fibro-odontoma.

PMID- 18810923
TI  - [Expert activities in surgery].

PMID- 18810924
TI  - [Experience with radiofrequency termoablation of brain tumors].
AB  - Together with tissue sampling stereotaxy in neurooncology makes also targeted
      intervention such as brain tumor radiofrequency thermoablation possible. In the
      paper authors present their experience with navigated radiofrequency
      thermoablation in 18 patients. Cerebral metastasis was the treated lesion in 5
      patients, 8 patients were operated on for brain glioma and 3 for pituitary
      adenoma. In 2 patients radiofrequency thermoablation of pituitary gland was
      undertaken to treat malignant pain or refractory diabetes. Presurgical planning
      using stereotactic software was utilised in all patient. In one patient it was
      necessary to perform tumor debulking because the local oedema of pituitary
      adenoma was threatening both optic nerves. Radiofrequency thermoablation is
      advantageous technique in circumscribed lesions, not exceeding 3 cm diameter,
      deeply seated. Perilesional oedema with intracranial hypertension is surgical
      limitation. Good tolerance of minimally invasive surgery and the possibility of
      biopsy sampling before radiofrequency thermoablation is an advantageous feature.
      Infiltrative growth of glial neoplasm together with irregular shape is the
      limitation of radiofrequency thermoablation in brain gliomas.

PMID- 18810925
TI  - Ischemic affection of the spinal cord as a result of the blunt thoracic trauma--a
      case report.
AB  - Authors present the case of a patient who suffered the blunt thoracic trauma. In
      the clinical picture there dominated the paraplegia of both the lower
      extremities. Due to the weakened breathing on the right side the urgent thoracic
      drainage was performed. For circulation instability and amount of blood passing
      out of the drain an urgent thoracotomy was indicated even prior to the CT or MRI.
      During the operation bleeding from the Adamkiewicz's artery was spotted and
      sanated. After the postoperative stabilization the CT and MRI investigations
      proved the spinal cord ischemia as a cause of the local damage.

PMID- 18810926
TI  - [Re-expansion pulmonary edema as a complication of a spontaneous pneumothorax
      drainage--a case review].
AB  - Reexpansion pulmonary edema is an iatrogenic complication occurring after
      reinflation of the collapsed lung of a patient with pneumothorax or fluidothorax.
      The following risk factors have been associated with reexpansion pulmonary edema:
      younger age, longer duration of a lung collapse, its large extend and a quick
      lung reexpansion. We report a case of 26-years-old man. The patient was admited
      to the second surgical clinic FNLP, Kosice because of a spontaneous pneumothorax.
      A chest tube was inserted in local anesthesia in the right anterior axilar line
      and the fourth intercostal space. An active negative pressure of 20 cm H2O was
      applied. Dyspnea, decrease of blood pressure, tachycardia, tachypnoe and
      expectoration of pink sputum were recorded after negative pressure application.
      Oxygen saturation decreased to 90% despite the addition of oxygen.
      Glucocorticoids, diuretic stimulants, analgesic and bronchodilatators were
      administered. Chest X-rays and computer tomography showed a strong ipsilateral
      pulmonary edema and an incipient contralateral pulmonary edema. The patient was
      stabilized and after 16 hours continuous oxygen administration was not longer
      needed. Because of continuous pneumothorax, a video assisted thoracoscopic
      surgery was performed on the seventh day after the chest tube insertion. After 13
      days of hospitalization the patient was discharged in good condition without any
      further complications to the ambulatory care. Reexpansion pulmonary edema is a
      rare complication of the chest tube insertion and thoracocentesis because of
      pneumothorax and fluidothorax. The mortality of reexpansion pulmonary edema
      reaches up to 20%. Chest tube insertion and thoracocentesis are therapeutic
      procedures to be performed solely on medical department which can provide
      artificial lung ventilation.

PMID- 18810927
TI  - [A female patient with heart fibrosarcoma. A case review].
AB  - Authors are in their announcement describing a case of a patient with
      fibrosarcoma of a left atrium, who was treated on Cardiosurgery department in
      Hospital of Ceske Budejovice. Symptoms, clinical signs and development of this
      disease are described in the text. There are also information relating cardiac
      sarcomas, management of their diagnostics and treatment.

PMID- 18810928
TI  - [Stents--palliative and curative management of esophageal conditions. Seven-year
      surgical experience].
AB  - The authors present their experience with endoscopic introduction of stents into
      esophagus and cardia based on data collected from a group of 520 patients. Their
      study included both paliative management of stenoses in carcinomas of the
      esophagus and cardia, as well as management of other esophageal conditions,
      including fistules, perforations and various types of stenoses, including the use
      of novel absorbable stents.

PMID- 18810929
TI  - [Pseudoaneurysm of the hepatic artery presenting with hemobilia--a complication
      of laparoscopic cholecystectomy].
AB  - INTRODUCTION: Hemobilia, defined as a bleeding into the bile duct, is a rare
      disease. One of its infrequent causes is a hepatic artery pseudoaneurysm, usually
      developed after arterial iatrogenic leasion. MATERIAL AND METHODS: A case review,
      presenting right hepatic artery pseudoaneurysm with a biliovascular fistula as a
      consequence of hepatic artery and bile duct injuries during "uncomplicated"
      laparoscopic cholecystectomy. DISCUSSION: Bile duct injury is one of the most
      serious complication after laparoscopic cholecystectomy. Hepatic artery may be
      injured simultaneously, resulting in the pseudoaneurysm and/or biliovascular
      fistula, presenting with hemobilia. Time interval from the injury to symptoms
      widely varies from few hours to weeks or even several months. CONCLUSION: Melena
      or hematemesis after recent laparoscopic cholecystectomy should be always
      suspicious from hepatic artery and/or bile duct injuries, manifesting with
      hemobilia.

PMID- 18810930
TI  - [Rare cases of extensive retroperitoneal liposarcomas].
AB  - INTRODUCTION: Liposarcomas of the retroperitoneal area (LSRP) are rare
      mesenchymal tumour, which are literary ranked among the retroperitoneal soft
      tissue sarcomas, they can reach enormous size, while patients complains aren't
      distinctive. The most common symptoms are abdominal discomfort and distention of
      abdominal volume with a palpable resistention. The only successful treatment of
      this tumor is surgical exstirpation. CASE REPORT 1: 77-year-old patient was
      investigated because of gradually accruing size of the abdomen. There was a
      lipoid tumour in the peritoneal cavity shown by computed tomography, suspected
      coming out of the retroperitoneal area. During the operation we found out giant
      well-differentiated liposarcoma which grew from the retroperitoneal area.
      Postoperative period was complicated by bleeding and consequently by MOF. 14th
      postoperative day patient died. Dissection finding was another location of
      liposarcomas in the retroperitoneal area. CASE REPORT 2: 66-year-old patient was
      investigated because of increasing girth. Abdominal ultrasonography and CT
      displayed adipoid formation which filled up most of the peritoneal cavity with
      compression of surrounding organs. The tumour was completely resected during
      operation. The patient has been followed in dispensatory for two years without
      any signs of recurrence of the illness. DISCUSSION: Liposarcomas are the most
      frequent histological type among primary retroperitoneal sarcomas. Metastatic
      potential of LSRP is low but these tumors often recur locally. In diagnostics and
      in follow-up are essential CT and MRI. Successful therapy is radical resection.
      It could be difficult to distinguish giant well-differentiated liposarcomas from
      normal retroperitoneal fat. Incomplete resection is a palliation operation
      without chance for long survival.

PMID- 18810931
TI  - [Post-gastrectomy reconstruction].
AB  - AIM: Authors present review of current opinion in reconstruction of
      gastrointestinal tract after gastrectomy, in pouch benefit and benefit of
      retaining of the duodenum in food transit, and the importance of antireflux
      procedure. METHOD: Authors searched the Medline database for current trials
      regarding the reconstruction of gastrointestinal tract after gastrectomy. The key
      words were gastrectomy, reconstruction, and upper GI. The search was limited to
      those languages: English, German, and Czech. The authors identified 41 trials
      altogether. The trials were analysed regarding the pouch benefit and the
      retaining of duodenum in food transit. The comparison was done. CONCLUSION: The
      trials' results are not homogenous. Many patients are not possible to be
      evaluated because of the tumor recurrence with weight loss and other symptoms.
      There is no ideal reconstruction according to the trials. Patients can benefit
      from the reconstruction retaining the duodenum in food transit and with pouch
      creation. The retained duodenum in food transit is anormal stage from the
      anatomical and physiological view. In the case that pouch allows the proportional
      evacuation of food, the retaining of duodenum is advantageous. The pouch combined
      with antireflux procedure has a potential to improve life duality from longer
      perspective. On the other side, some authors present opinion that the
      reconstruction with pouch is too complicated with worse patient perioperative
      tolerance and its benefit is minimal. There is a very small number of prospective
      randomized trials which present a very small number of patients without
      statistical significance. It is important to perform a larger prospective
      randomized trial.

PMID- 18810932
TI  - [Massive hemothorax following canylation of the subcalvian vein--a case review].
AB  - INTRODUCTION: Cannulation v. subclavia is connected with many complications.
      Haemothorax is occurs approximately in 2% of cases. Surgical revision is
      indicated immediately if a major blood loss or a circulation insufficiency occur.
      Surgical treatment of bleeding in cupola of pleural cavity is due to its bad
      accesability difficult and conventional surgical methods aren't sufficient. In
      these cases one can use local haemostyptic. CASE REPORT: The authors present a
      case review of a 36-years old patient with a developed massive haemothorax on the
      left side post a catheterization of v. subclavia. During surgical revision it was
      found out that a source of bleeding in superior thoracic aperture is present. It
      wasn't able to be stopped by classical surgical procedure. TachoSil and Arista
      preparations were used in this case with a good effect.

PMID- 18810933
TI  - [Pectoralis maior tendon rupture and anabolic steroids in anamnesis--a case
      review].
AB  - INTRODUCTION: Muscle building, gaining in popularity, and availability of
      anabolic steroids are connected with raised incidence of tendon injuries in
      uncommon locations. CASE REVIEW: The author describes a case of an injured body
      builder treated for the major pectoral muscle's tendon rupturing, and, later on,
      for the quadriceps tendon and distal bicipital tendon ruptures. The m. pectoralis
      major tendon rupture was managed surgically-including tendon reinsertion,
      temporary immobilization and gradual rehabilitation with dosed loading. The
      treatment resulted in full recovery and the patient was able to resume common and
      sport activities. DISCUSSION: The study assessed the role of steroids in
      development of tendon injuries, as well as their treatment methods. Based on his
      experience, the author, as well as other authors, favours indication for early
      surgical management to conservative treatment.

PMID- 18810934
TI  - Hybrid procedures in the treatment of pseudoaneurysms of the aortic arch--case
      report.
AB  - Classical surgical therapy of dilatation disorders of the aortic arch require
      extracorporeal circulation, selective brain perfusion and/or deep hypothermia and
      it is still associated with very high mortality and morbidity. Endovascular
      therapy has until recently indicated only been in cases when the disease did not
      affect the area of the origins of the main branches within the aortic arch. We
      are presenting a case report of a 68 year female patient with a vascular anomaly
      (arteria lusoria) and 2 pseudoaneurysms of the aortic arch between the origins of
      arteria carotis communis on the right and arteria carotis communis on the left,
      respectively between a. carotis communis on the left and arteria subclavia on the
      left, when we took advantage of a hybrid procedure in the therapy. The patient
      was treated by creating a new branching of the aortal arch using a prosthesis
      from the ascendant aorta and subsequently by an introduction of 2 stent-grafts to
      the aortic arch using femoral arteries.

PMID- 18810935
TI  - Coordinated care program cuts costs for members with chronic illness.

PMID- 18810936
TI  - California IPA wins even in slowing market.

PMID- 18810937
TI  - Social media provide cost-effective route to patient care.

PMID- 18810938
TI  - Coordinated care benefits children with special needs.

PMID- 18810940
TI  - I.T. lessons from the flood.

PMID- 18810939
TI  - Reader's perspective. Today's mobile computer carts are far more advanced and
      user-friendly than those sold two years ago. Agree.

PMID- 18810941
TI  - Wishing for a better EHR. Electronic health records users share their wish lists
      for added functionality.

PMID- 18810942
TI  - Winning the support of clinicians for I.T.

PMID- 18810943
TI  - Cutting and pasting in the OR.

PMID- 18810944
TI  - Following a moving target.

PMID- 18810945
TI  - A different kind of e-mail.

PMID- 18810947
TI  - Testing the PHR options.

PMID- 18810946
TI  - Help is at hand.

PMID- 18810948
TI  - What's taking so long?

PMID- 18810949
TI  - Clues to a catastrophe.

PMID- 18810950
TI  - Will they spit?

PMID- 18810951
TI  - Selling your medicine.

PMID- 18810952
TI  - Industrial entrapment.

PMID- 18810953
TI  - Dude, where's the ambulance?

PMID- 18810954
TI  - Behind the wheel. An interview with Les R. Becker. Interview by Raphael M
      Barishansky.

PMID- 18810955
TI  - Cardiocerebral resuscitation.
AB  - Cardiocerebral resuscitation (CCR) is a new approach to patients with out-of
      hospital cardiac arrest that has been shown to improve rates of neurologically
      intact survival by 250%-300% over the approach advocated by the 2000 American
      Heart Association guidelines. And EMS systems can realize these improvements
      without having to buy a single new gadget or device.

PMID- 18810956
TI  - You take my breaths away.

PMID- 18810957
TI  - But can they lift?
AB  - Anybody who screens EMS field candidates will tell you, not just anybody can do
      EMS. You need a good brain to pass your tests, earn your certs and think your way
      through calls. You need the manual dexterity and multitasking capabilities of an
      ED nurse. You need the maturity and psychomotor skills of a professional driver.
      You need a warm and willing heart. And, no matter how talented you are in all of
      those areas, you need to be able to lift--often, a lot.

PMID- 18810958
TI  - Pediatric toxicology: Part 3. What EMS providers need to know about "one-pill
      killers".
AB  - As discussed in Parts 1 and 2 in the April and May issues, most toxic exposures
      in children under 6 years old are secondary to exploration rather than
      intentional attempts to harm and therefore do not involve enough substance to
      cause significant toxicity. It is not until the teen years that toxic exposures
      with intent to cause personal harm begin to occur. There are several substances,
      however, that can result in significant toxicity, even when taken at low doses.
      These are referred to as "one-pill" or "one-dose" killers. Although it may take
      more than one pill or dose for death to occur, this is a good tenet to remember,
      as low doses of these substances can indeed cause significant toxicity or death.
      Therefore, it is imperative that prehospital providers be familiar with both the
      generic and trade names of these medications so exposure can be recognized and
      appropriate treatment initiated.

PMID- 18810959
TI  - Beyond the basics: immune response.
AB  - The human immune response is arguably among the most difficult processes for an
      EMS provider to understand. The immune system provides front-line defense to any
      potentially inflammatory process, with the goal of destroying or inactivating
      pathogens, abnormal cells and foreign substances. The system includes the thymus,
      spleen, lymph nodes, lymphoid tissues (as in the GI tract and bone marrow),
      macrophages, lymphocytes, including B and T cells, and antibodies, among others.
      On the surface, the skin and stomach acid serve as physical barriers to invasion.
      This article will primarily concentrate on the immune response to allergies, but
      will discuss some other immune disorders to illustrate the role of the immune
      system in common disease processes.

PMID- 18810960
TI  - Ready to roll.
AB  - All EMS systems must have a reliable ambulance fleet to provide timely and
      effective care to their constituents. In order to do so, an effective strategic
      plan for this area of operations must be in place and followed. The intent is to
      provide a cost-effective solution that provides a reliable transportation
      resource for the system that is supported in a top-down approach throughout the
      organization such that it becomes an integral part of its cultural fabric.

PMID- 18810961
TI  - Designing for safety.

PMID- 18810962
TI  - It takes a village.

PMID- 18810963
TI  - Studies on the toxicity of acetone, acrolein and carbon dioxide on stored-product
      insects and wheat seed.
AB  - In laboratory experiments toxicity of acetone, acrolein and carbon dioxide were
      investigated against 4 species of stored-product insects. In all experiments,
      acrolein was the most toxic compound to the tested insects. In empty-space
      trials, estimated LD50 values of acrolein for adults of Tribolium castaneum
      (Herbst) (Tenebrionidae), Rhizopertha dominica (F.) (Bostrychidae), Sitophilus
      oryzae L. (Curculionidae) and Oryzaephilus surinamensis L. (Silvanidae) were
      7.26, 6.09, 6.37 and 5.65 microl L(-1), respectively. Penetration tests revealed
      that acetone and acrolein vapors could penetrate into the wheat mass and kill
      concealed insects in interkernel spaces. Comparison of LD50 values of acrolein
      between empty-space tests and penetration experiments indicated that the increase
      in penetration toxicity was 4.96, 4.54, 3.64 and 3.43-fold for T. castaneum, R.
      dominica, S. oryzae and O. surinamensis, respectively. The effect of carbon
      dioxide on the toxicity of acrolein and acetone was synergistic. In the hidden
      infestation trials, the acrolein vapors destroyed the developmental stages of S.
      oryzae concealed inside the wheat kernels and resulted in a complete control with
      concentration of 80 microl L(-1) for 24 h and subsequently observed during 8
      weeks after the exposure. Wheat germination and plumule length was reduced
      following exposure to all doses of acrolein. Acetone and carbon dioxide were
      harmless to wheat seed viability. The mixture of carbon dioxide with acrolein can
      be considered as a potential fumigant for replacing methyl bromide or phosphine
      under ambient storage conditions specifically in empty-space fumigations.

PMID- 18810964
TI  - Biosorption of copper, nickel and manganese using non-living biomass of marine
      alga, Ulva lactuca.
AB  - The adsorption of Cu2+, Ni2+ and Mn2+ onto the marine algal biomass of Ulva
      lactuca was investigated in single and multimetal solutions. This study was
      intended to determine the role of different pH values (2-8) on the biosorption of
      metals at different concentrations (10, 20 and 30 mg L(-1)). The biosorption
      capacity of Cu2+, Ni2+ and Mn2+ for 10 mg L(-1) was the same as 20 and 30 mg L(
      1), increase with increasing pH up to pH 5.0 and then decreased, in single and
      multimetal solutions. The optimum pH value was observed in the pH range 4-5 for
      Cu2+ and pH 5-6 for Ni2+ and Mn2+. The maximum biosorption capacities of tested
      alga for Cu2+, Ni2+ and Mn2+ were 92, 80 and 75%, respectively in single metal
      solution at 10 mg L(-1) and pH 5.0. At a further increase of pH (8.0) the
      biosorption process for Cu2+, Ni2+ and Mn2+ (75, 69 and 63%, respectively at 10
      mg L(-1)) was decreased. The minimum biosorptions were 60, 49 and 44% for Cu2+,
      Ni2+ and Mn2+, respectively in single metal solution at 10 mg L(-1) and pH 2.0.
      In the multimetal solution, algal biomass exhibited the maximum and the minimum
      biosorption capacity at different pH values the same as in single metal solution.
      The inhibitory role of other ions on sorption process can be well observed in
      multimetal mixture, where biosorption capacity of Cu2+, Ni2+ and Mn2+ were
      significantly decreased in the multimetal solutions. The maximum biosorption was
      recorded for Cu2+ (83%) in solution of Cu2+ + Mn2+, Mn2+ (67%) in solution of Ni2
      + Mn2+ and for Ni2+ (74%) in solution of Ni2+ + Mn2+ at the concentration 10 mg
      L(-1) and pH 5.0. The observed reduction in the biosorption of Cu2+, Ni2+ and
      Mn2+ (65, 57 and 52%, respectively at 10 mg L(-1) and pH 5.0) was more pronounced
      in the multimetal solution of Cu2 + Ni2+ + Mn2+ as compared with single metal
      solution. The results demonstrated that the affinity of the tested alga for
      sorption of the investigated metal ions in single and multimetal solutions runs
      in the order Cu2+ > Ni2+ > Mn2+. Biosorption equilibrium was established by the
      Langmuir and Freundlich isotherm models. According to the analyses conducted, the
      biosorption of Cu2+, Ni2+ and Mn2+ to Ulva lactuca was more consistent with
      Freundlich isotherm.

PMID- 18810965
TI  - An analysis on organic acids contents in ripe fruits of fifteen Mao Luang
      (Antidesma bunius) cultivars, harvested from dipterocarp forest of Phupan Valley
      in northeast Thailand.
AB  - This experiment was carried out in the rainy season (May-October) of the 2006 at
      the Department of Biotechnology, Faculty of Technology, Mahasarakham University,
      Mahasarakham 44000, Thailand to analyse organic acids contents in ripe fruits of
      fifteen Mao Luang cultivars harvested from dipterocarp forest, Phupan Valley,
      Sakon Nakhon, Northeast Thailand. The experiment was laid in a Completely
      Randomised Design (CRD) with four replications. The fifteen Mao Luang cultivars
      were used as treatments. The results showed that there were two groups of organic
      acids contents in ripe fruits of Mao Luang cultivars i.e., major and minor. The
      major group of organic acids includes: tartaric acid (7.97-12.16 mg g(-1) of
      fresh weight), ascorbic acid (10.01-16.55 mg g(-1) of fresh weight), citric acid
      (4.44-11.73 mg g(-1) of fresh weight) and benzoic acid (8.13-17.43 mg g(-1) of
      fresh weight) and the minor group includes malic acid (3.05-4.52 mg g(-1) of
      fresh weight), lactic acid (1.12-4.09 mg g(-1) of fresh weight), oxalic acid
      (1.00-1.45 mg g(-1) of fresh weight) and acetic acid (0.19-0.69 mg g(-1) of fresh
      weight). Khumlhai cultivar gave the highest amount of ascorbic acid followed by
      Lompat, Phuchong, Sangkrow 2 and Maelookdog cultivars. Sangkrow 2 and Phuchong
      cultivars gave the highest ratio between tartaric and malic acids. Total soluble
      solid content (TSS%) was highest with Sangkrow 5 cultivar, whilst Total Organic
      Acids (TOA) was highest with Phuchong cultivar and ratio between TSS:TOA was
      highest with Sangkrow 2 cultivar. Juice % was highest with both Sangkrow 2 and 3
      cultivars, whilst Fapratan and Lompat cultivars ranked the second.

PMID- 18810966
TI  - Geographical information system (GIS) mapping of spatio-temporal pollution status
      of rivers in Ibadan, Nigeria.
AB  - More accurate spatio-temporal predictions of urban environment are needed as a
      basis for assessing exposures as a part of environmental studies and to inform
      urban protection policy and management. In this study, an information system was
      developed to manage the physico-chemical pollution information of Ibadan river
      system, Oyo State, Southwest Nigeria. The study took into account the seasonal
      influences of point and non-point discharges on the levels of physico-chemical
      parameters. The overall sensitivity of the watershed to physicochemical
      environmental pollution revealed that during dry season, of the 22 (100%) sample
      points, only 3 (13.6%) were unpolluted; 6 (27.3%) were slightly polluted;
      10(45.4%) were moderately polluted; 2 (9.1%) were seriously polluted and 1 (4.5%)
      was exceptionally polluted. During rainy season, 3 (13.6%) were unpolluted; 7
      (31.8%) were slightly polluted; 9 (40.9%) were moderately polluted; 2 (9.1%) were
      seriously polluted and 1 (4.5%) was exceptionally polluted. There is a
      considerable environmental risk associated with the present level of pollution of
      the Ibadan river water body on fish health and biodiversity. This research
      provides a basis for aquatic management and assist in policy making at national
      and international levels. Appropriate strategies for the control of point and non
      point pollution sources, amendments and enforcement of legislation should be
      developed.

PMID- 18810967
TI  - Effect of thermal processing of palm sap on the physico-chemical composition of
      traditional palm sugar.
AB  - During the production of palm sugar, the palm sap (Arenga pinnata) is heated up
      to 150 degrees C. Besides the hydrolysis of carbohydrate to generate reducing
      sugars and degradation of amino acid, many physicochemical changes produced at
      all these temperatures, having a significant impact on the overall quality of
      palm sugar. In this study, changes in physico-chemical properties of the palm sap
      due to heat processing were investigated. Analysis of colour, soluble solid, pH,
      temperature, sugar and amino acid concentration was determinant. The results
      showed clearly that the heating process at these high temperatures was necessary
      to create an environment which was rich in essential precursors for subsequent
      reactions such as Maillard reaction. Chemical compounds that showed drastic
      changes in concentration were polar side chain amino acids especially glutamine,
      asparagine and arginine as well as sucrose and pH value. Other quality
      characteristics of palm sugar based on colour and soluble solids (Brix) shared an
      increase in concentration as a function of time.

PMID- 18810968
TI  - An analysis on flavonoids contents in Mao Luang fruits of fifteen cultivars
      (Antidesma bunius), grown in northeast Thailand.
AB  - This investigation was carried out at the Department of Biotechnology, Faculty of
      Technology, Mahasarakham University, Mahasarakham Province, Northeast Thailand.
      The study aimed to analyze flavonoids contents in ripe fruits of fifteen Mao
      Luang cultivars (Antidesma bunius) harvested from dipterocarp forest of the
      mountainous areas of Phupan Valley, Sakon Nakhon Province, Northeast Thailand.
      The experiment was laid in a Completely Randomised Design (CRD) with five
      replications. The fifteen cultivars were used as treatments. An amount of 2 kg of
      ripe fruits of each cultivar was collected and extracted for juice solutions. The
      analysis was carried out with the use of RP-HPLC laboratory system. The results
      showed that fruits of the fifteen Mao Luang cultivars contained three different
      kinds of flavonoids, i.e., catechin, procyanidin B1 and procyanidin B2. These
      three chemical compounds were the major flavonoids in all analyzed fruit samples
      of the fifteen cultivars. The highest amount of procyanidin B1 was found with
      Lompat followed by Maeloogdog with values of 4122.75 and 3993.88 mg 100 g(-1) of
      fresh weight, respectively and the highest amount of procyanidin B2 was found
      with Sangkrow 2 followed by Fapratan with values of 5,006.39 and 3,689.42 mg 100
      g(-1) of fresh weight, respectively. Catechin contents in fruits of the fifteen
      cultivars varied from 73.39 to 316.22 mg 100 g(-1) of fresh weight for Sangkrow 5
      and Fapratan, respectively where Fapratan was the highest among the fifteen
      cultivars followed by Sangkrow 2 with values of 316.22 and 175.40 mg 100 g(-1) of
      fresh weight, respectively. In terms of grand total amounts of flavonoids,
      Sangkrow 2 was the best followed by Fapratan, Sangkrow 1 and Maeloogdog, whilst
      the rest were of secondary importance.

PMID- 18810969
TI  - Physico-chemical characteristics and total quality of date palm varieties grown
      in the southern of Tunisia.
AB  - The date palm, Phoenix dactylifera, is a palm extensively cultivated for its
      edible fruit. The chemical composition and the water content of ten Tunisian date
      varieties were determined. For all analysis, the Deglet Nour variety was taken as
      reference. Compositional analysis showed that the littoral varieties were very
      rich in reducing sugars (26 to 51%) than Deglet Nour which was rich in sucrose
      (54%). The relative results of the moisture content showed that the littoral
      varieties were classified as soft dates. The vitamin C analysis showed that the
      littoral varieties were very rich in this compound (24 to 46 mg/100 g) than
      Deglet Nour (1.12 mg/100 g). The mineral analysis showed that the littoral dates
      were relatively rich in potassium (283 to 733 mg/100 g) and presented a weak
      content in sodium (0.06 to 0.09 mg/100 g).

PMID- 18810970
TI  - Optimizing regeneration condition in chickpea (Cicer arietinum L.).
AB  - In this study, multiple shoot induction and whole plant regeneration from
      decapitated embryo axes of three chick peal genotypes including MCC252, MCC283
      and MCC505 were evaluated on modified Murashige and Skoog's medium (MMS) which,
      its vitamins were replaced by vitamins of B5 medium, supplemented with varied
      concentration of thidiazuron (0.1, 0.2 mg L(-1)) or 6-benzylaminopurin (1,2 mg L(
      1)) or zeatin (1, 2 mg L(-1)) treatments. BAP was found to be the most effective
      cytokinin in normal multiple shoot induction. Shoots were elongated on growth
      regulator-free medium and then rooted on two media containing 1/4 MMS salts and
      B5 vitamins + 3% sucrose + 0.8% agar with indol-3-butyric acid (0.4 or 1 mg L(
      1)). The highest rooting frequency resulted in a medium including 0.4 mg L(-1)
      IBA. It was found that different shoot induction media also positively affected
      rooting, where a medium with 2 mg L(-1) BAP in MCC252/MCC505 and a medium with 2
      mg L(-1) zeatin in MCC283 were the best media in shoot induction that produced
      high frequency, thick spread roots. Plantlets were preliminary acclimatized in
      liquid medium (1/4 MMS salts and B5 vitamins + 3% sucrose + 0.4 mg L(-1) IBA) for
      7 to 14 days, then transferred to pots filled by cocopit: perlite (1:1) and kept
      in a growth chamber until their shoots and roots were well developed. This
      resulted in more than 70% survival rate.

PMID- 18810971
TI  - Functional and numerical responses of Eretmocerus mundus Mercet (Hymenoptera:
      Aphelinidae) parasitizing cotton whitefly, Bemisia tabaci Gennadius (Homoptera:
      Aleyrodidae).
AB  - Laboratory experiments were conducted to measure the functional and numerical
      responses of Eretmocerus mundus Mercet parasitizing cotton whitefly, Bemisia
      tabaci Gennadius. Parasitoids were isolated singly for 24 h in 5 cm petri dishes
      with either 5, 10, 20, 40, 60 or 100 second nymphal stages of B. tabaci. Results
      showed a typical type II functional response, with up to 43.2 hosts attacked when
      100 hosts were provided. The rate of attack and handling time were 0.0465 and
      0.3341 days, respectively. At above mentioned densities, the parasitoids lived an
      average of approximately 4 days. At host densities of < or =20 host/day, the
      total number of eggs laid was limited by the number of hosts available. Total
      fecundity was highest with an average of 196 eggs/female at density 100.

PMID- 18810972
TI  - Some morphological and anatomical studies of leaves and flowers of Murraya
      paniculata (Jack) Linn. in vivo and in vitro.
AB  - In the present study, various explants of Murraya paniculata (Jack) Linn., such
      as cotyledons, shoots and young stems were cultured on MS medium supplemented
      with various concentrations of Benzyl Amino Purine (BAP) under 25 +/- 1 degree C
      with 16 h light and 8 h dark and also 8 h light and 16 h dark to obtain complete
      plant regeneration. In vitro flowering was observed from shoot explants cultured
      on MS supplemented with 0.5-2.0 mg L(-1) Naphthalene Acetic Acid (NAA) and also
      on MS basal medium under similar conditions. The leaves and flowers obtained from
      both in vivo and in vitro conditions were examined and compared. Morphological
      studies such as leaf clearing, epidermal peeling were studied using light and
      scanning electron microscope. Macromorphological studies of the flowers produced
      from in vivo and in vitro conditions were also examined. Morphologically, there
      were no differences between in vivo and in vitro flowers except the flowers
      produced from tissue culture systems were smaller in size with protruding
      stigmas. Differences were also found in the number of layers of palisade cells
      and the presence or absence of epicuticle layer of the leaves. Leaves produced
      from tissue culture system were smaller in size with membranous texture. Stomata
      were present only on the abaxial surfaces of both in vivo and in vitro leaves but
      the stomata were raised above the epidermis in the latter.

PMID- 18810973
TI  - Cloprostenol injection improves reproductive characteristics in low libido
      Iranian Holstein bulls.
AB  - The objective of this study was to determine whether injections of Cloprostenol
      (PGF2alpha analog) in low libido Holstein bulls can improve seminal
      characteristics and libido. Ten low libido Iranian Holstein bulls were randomly
      assigned to two groups and received; (1) 250 microg ofCloprostenol (n=5) or (2) 2
      mL of saline (n=5) 30 min prior to collection of semen 2 days per week for 2
      months. Reaction time was significantly decreased in treatment group. Duration of
      ejaculation was significantly increased in treatment group. Semen volume and
      sperm concentration were greater in treated bulls in compare with controls. The
      percentage of morphologically normal sperm cells, percentage of live sperm cells,
      motile sperm cells and post-thaw motile sperm cells were not affected by
      treatment. Plasma testosterone concentrations were increased approximately two
      fold after Cloprostenol injection. Overall, injection of Cloprostenol at this
      dosage and frequency increased libido, semen volume, sperm concentration and
      plasma testosterone concentration in low libido Holstein bulls.

PMID- 18810974
TI  - The study of adrenal chromaffin of fish, Carassius auratus (Toleostei).
AB  - In C. auratus the adrenal chramaffin tissue is situated around the posterior
      cardinal veins, in the head kidney. Chromaffin tissue consists of two types of
      cells containing secretory granules, adrenaline and nor adrenaline cells. The
      cells produced catecholamine hormones. Adrenaline cell contains electron-lucent
      granules, whereas nor adrenaline cells possesses electron-dense granules.
      Cholinergic fibers embedded in the head kidney innervated the chromaffin cell.
      Two types of secretory structures, synaptic vesicles and secretory granules are
      found within the presynaptic terminal. Secretory granules discharge their
      contests, as neuropeptide in non synaptic area of nerve terminal by exocytosis,
      whereas synaptic vesicles discharge their contents as neurotransmitters at the
      synaptic thickening (active zone) in the presynaptic terminal by exocytosis.

PMID- 18810975
TI  - Novel mutation in the EXT-1 gene in an Iranian family affected with hereditary
      multiple exostoses.
AB  - Identification of casual mutations in Hereditary Multiple Exostoses (HME) is
      important because of similar conditions in which multiple exostoses occur.
      Therefore mutation analysis can help to confirm the clinical diagnosis and to
      improve the management of therapy. HME is an inherited disorder of bone growth.
      HME can be referred to by various names such as Heredity Multiple Exostoses,
      Hereditary Multiple Osteochondromata, Multiple Carthaginous Exostoses, etc.
      People who have HME grow exostoses, or bony bumps, on their bones which can vary
      in size, location and number depending on the individual. HME is inherited in an
      autosomal dominant manner with an estimated prevalence of 1/50,000 in western
      countries. At least three loci (EXT1, EXT2 and EXT3) thought to be involved in
      this skeletal disease. Approximately 90% of affected families possess mutations
      in the coding regions of EXT1 and EXT2 genes and the majority of these mutations
      cause loss of function. EXT1 and EXT2 genes encode related members of a putative
      tumor suppressor family. In this first report from Iran we identified a frame
      shift mutation (1100-1101 insA) in exon 3 of EXT1 gene in a family being
      suspicious of HME. This mutation leads to a premature stop codon and previously
      not described. Additionally, we have found an unreported silent mutation in the
      exon six of EXT1 gene with uncertain significance.

PMID- 18810976
TI  - Effects of Zn rates and application forms on protein and some micronutrients
      accumulation in common bean (Phaseolus vulgaris L.).
AB  - In order to investigation the effects of Zn rates and application forms on
      protein and element contents (Fe, Cu, Mn, N and Zn) in bean plant, an experiment
      was conducted as a factorial based on completely randomized design at greenhouse
      conditions during 2006. Treatments were included zinc rates in 4 levels (10, 20,
      30 and 40 mg Zn kg(-1) soil(-1) in ZnSO4 source) and 3 application forms (soil
      application, seed pelleting and foliar spraying). Results showed that Zn rates
      had significant effect on accumulation of Zn, Cu, Mn and N in bean leaves.
      Nitrogen accumulation in leaves reduced with increasing of zinc in the soil.
      Among Zn application forms, spray application had the highest accumulation of Fe,
      Zn and Mn in leaves (423.17, 282.89 and 88.17 mg kg(-1), respectively). The
      highest Zn content in seed was observed in 20 and 40 mg Zn kg(-1) soil(-1) levels
      (46.39 and 45.62 mg kg(-1), respectively). Meanwhile, all treatments of Zn (both
      rate and application) had not significant effects on Cu and Mn accumulation in
      bean seeds. According to interaction effects between Zn rates and application
      forms, the highest Fe content in seed was observed when 40 mg kg(-1) soil(-1) of
      Zn was applied as foliar spraying. The seed protein content nearly was stable
      while Zn levels was increased from 20 to 40 mg Zn kg(-1) soil(-1). Grain yield
      had significant correlation to zinc and Cu of leaves but, biomass had significant
      and negative correlation to Zn content of leaves at p < 0.05% probability levels.

PMID- 18810977
TI  - Study on the prevalence of dairy cattle lameness and its effects of production
      indices in Iran. A locomotion scoring base study.
AB  - In this current study, prevalence of lameness was detected and its changes during
      different parities, Days in Milk (DIM) and milk production were studies. In
      addition, effects of lameness on Open Days (OD) and Service per Conception (S/C)
      were studied. Three dairy farms on three scales (1: Large, approximately 900
      milking cows, 2: Medium, approximately 100 milking cows and 3: Small,
      approximately 20 milking cows) were watched for lameness in 2005-2006. Locomotion
      Scoring (LS) by Sprecher method (1-5 point scale) has been done by videoing of
      the animals at the exit of the milking parlor. Videos were reviewed by two expert
      and mean of the each score used as score of the animal, cows with scores 1 and 2
      recorded as non-lame and 3, 4 and 5 as lame cows. The average score of the
      lameness in autumn and spring recorded as 2.47 and 2.73, respectively that was
      higher significantly in spring. LS has been increased significantly by increasing
      parity and DIM, as highest scores were recorded in parity 4 and DIM 240-300. No
      significant differences between lame and non-lame cows were recorded in according
      to their milk production. The highest (percent in lame cows) scores were recorded
      in high producing cows. No significant difference in milk production has been
      recorded in different LS. However the average production of milk in lame cows
      were 1.08 L day(-1) less that non-lame cows. The average OD of the lame cows was
      significantly longer (52 days) than non-lame cows. Lame cows needed significantly
      higher service/conception (one) than non-lame cows. Median of OD and S/C has been
      increased by LS.

PMID- 18810978
TI  - Introducing the Karayaka sheep breed with its traits and influencing factors.
AB  - This study was planned to express the detailed traits of Karayaka sheep reared in
      Tokat province, also influencing factors on the traits were evaluated. While year
      effect was significant on 8 weeks weight, scanning weight, fat depth and muscle
      area, all the evaluated traits including birth weight and muscle depth were
      significantly affected by season (p < 0.05). Dam age was significant on birth
      weight (p < 0.05). Birth weight and 8 week weight were significantly affected by
      sex and birth type. Sex effect has been appeared on muscle depth while birth type
      effect has been detected on scanning weight (p < 0.05). While the strongest
      phenotypic correlation coefficient was detected between muscle depth and muscle
      area, the weakest ones were found between birth weight and scanning traits.

PMID- 18810979
TI  - Plant regeneration and floral bud formation from intact floral parts of African
      violet (Saintpaulia ionantha H. Wendl.) cultured in vitro.
AB  - Intact immature flower buds of African violet (Saintpaulia ionantha H. Wendl.)
      were used as explant sources for in vitro studies. The effect of exogenous
      hormones, NAA and BAP on the indirect organogenesis of this species was observed.
      Callus was formed on the cut end (base) of pedicels of floral buds where they
      were in contact with the medium. When maintained on the same medium, callus was
      differentiated into adventitious shoots after 10 weeks in culture. MS media
      supplemented with 2.0 mg L(-1) NAA and 1.0 mg L(-1) BAP gave the highest number
      of sterile or vegetative floral buds from the surface of callus of the explants,
      but these buds failed to develop further. The floral buds were expanded as
      abnormal flowers. The floral structures were smaller in size compared to intact
      flowers. Petals (corolla) were white to purple in colour but did not form any
      reproductive organs, i.e., stamens or pistils. All sterile or vegetative floral
      buds and abnormal flowers survived for 3 months in culture but failed to reach
      anthesis.

PMID- 18810980
TI  - Cardiac involvement of major thalassemia and evaluation of total serum creatine
      kinase and creatine kinase-mB isoenzyme and cardiac troponinI in these patients.
AB  - The goal of this study was the evaluation of specific markers of myocardial
      injury that includes CK-MB and troponin I in major thalassemic patients. Regular
      blood transfusion is the main treatment in major thalassemia. One of the most
      important complications of regular blood transfusion is iron overload that
      eventually involves many organs like heart and cause myocardial injury. Sixty
      patients with transfusion-dependent major thalassemia, at the age range of 8 to
      15 years in Tabriz Pediatric Medical Center were chosen. Measurement of Hb, Hct
      and serum ferritin were performed in hospital laboratory, but total serum
      Creatine Kinase (CK) by photometric and isoenzyme of CK-MB by immunologic DGKC
      and cardiac troponin I (cTnI) were tested by ELISA methods in Shaheed Madani
      heart center laboratory before blood transfusion. For all patients
      echocardiography and ECG assessment of cardiac function were done by a pediatric
      cardiologist and results were statistically analyzed. Forty nine patients (group
      A) had normal left ventricular ejection fraction (LVEF = 50-70%) and 11 patients
      (group B) had reduced LVEF (20-45%). There was no statistical difference between
      two groups in average volume of blood transfusion (p = 0.074). Although total CK
      and CK-MB isoenzyme were higher in group B but there was no statistically
      meaningful difference between two groups (p = 0.123, p = 0.111). Troponin I also
      was higher in group B but statistically analysis showed no correlation between
      cardiac function and troponin I level in these groups (p = 0.827). This study
      showed that cardiac markers are not helpful for recognition of cardiac
      involvement in major thalassemia.

PMID- 18810981
TI  - Gaucher disease: A 10 year old girl with anemia and huge spelenomegaly (a case
      report).
AB  - Gaucher's disease is a rare lipid storage disorder, affecting one in 40,000
      200,000 people and results from a genetic deficiency of the enzyme
      glucocerebrosidase (glucosylceramidase). We report a 10-year old Iranian girl
      with chief complaint of anemia from 8 years ago, managed for iron deficiency
      anemia. The patient had hepatomegaly associated with huge splenomegaly which was
      confirmed by sonography. No skeletal disorder was found. Bone marrow aspiration
      revealed typical Gaucher cells. Low level of beta-glucocerebrosidase enzyme
      activity confirmed the Gaucher disease. The patient is now under treatment with
      CEREZIME, a recombinant DNA modified form of glucocerebrosidase with good
      condition.

PMID- 18810982
TI  - [Asymmetry of voltage concentration boundary layers effect in double-membrane
      diffusive cell].
AB  - The aim of this work was to investigate the asymmetry of voltage concentration
      boundary layers effect in double-membrane diffusive cell, in which the membranes
      were fixed in horizontal planes. The research material consisted of flat,
      symmetrical and porous membrane of regenerated cellulose applied in the coil
      hemodialyzer and aqueous sodium chloride solutions. The studing of membrane
      electric voltages psi(o) and psi(s) were carried out in the series of two
      isothermal stages. In the first stage was established the psi(o)(t)
      characteristic in the conditions in which membranes M1 i M(r) were fixed
      vertically. In the second stage the psi(s)(t) characteristic was established in
      the situation in which M1 and M(r) membranes were fixed horizontally. In all
      stages the monitoring of membrane electrical voltages was carried out until the
      stationary state was achieved. The obtained results shows, that Psi(s) = psi(s)
      psi(o) is the non-linear function of concentrations (C(ms)/C(o)) of the solutions
      being in the ranges both central (C(ms)) and external (C(o)) in a double-membrane
      diffusive cell. It has been stated that this cell has the properties of asymmetry
      the voltage effect of the concentration boundary layers. The measure of these
      properties is an adequate asymmetry coefficient. The value of this effect depends
      on the concentration of the solutions and the configuration of double-membrane
      diffusive cell.

PMID- 18810983
TI  - Time evolution of NaCl flux through the microbial cellulose membrane with
      concentration polarization.
AB  - The method of solute permeability coefficient and solute fluxes appointment for
      the membrane, based on monitoring of changes of conductivity of electrolyte
      solutions was presented. It was stated that during mechanical stirring of
      solutions the coefficient of NaCl permeability for microbial cellulose membrane
      (Biofill) did not depend on configuration of the membrane system and
      concentrations of solutions. Time characteristics of NaCl flux through the
      membrane Biofill oriented in horizontal plane were measured and modeled. The
      changes of NaCl fluxes through the membrane Biofill caused by concentration
      boundary layers build up on both sides of the membrane depended on NaCl
      concentrations and configuration of the membrane system. The differences between
      fluxes in different configurations of the membrane system were observed after
      time depended on initial concentrations in chambers. After that time, for
      configuration with solution with higher density over the membrane (configuration
      B) the NaCl flux through the membrane was greater than for configuration with
      solution with lower density over the membrane (configuration A). Besides it was
      stated that the coefficient of concentration polarization for configuration B was
      higher than for configuration A for all studied NaCl concentrations. Increase of
      mean concentration in the membrane at the initial moment caused increase (for
      configuration B) and lack of changes (for configuration A) of concentration
      polarization coefficient in the steady state of the membrane system. The
      interpretation of experimental results was made on the basis of Kedem-Katchalsky
      equations for the membrane system.

PMID- 18810984
TI  - Comparison of 3T3 fibroblasts growth on alginate and polyasparagine (PAA)
      scaffolds in mouse model.
AB  - INTRODUCTION: The aim of this study was to evaluate polyasparagine (PAA), a new,
      promising scaffold. PAA was compared with alginate, which is used in cell
      transplantations and may be regarded as a standard. MATERIALS AND METHODS: In
      vitro cell viability on both scaffolds was assessed. C57B1 mice were injected s.
      c. alginate or PAA with or without 3T3 cells. After two months specimens from
      sites of injection were examined and blood samples were taken for enzymatic
      activity estimation. Cathepsin D activity and alpha1-antitrypsin levels were
      measured. RESULTS: In vitro cell viability was lowest on PAA and highest in
      control group. Increase in levels of enzymes measured was observed in response to
      PAA and alginate and was lower in case of polymer seeded with cells. Increase in
      alpha1-antitrypsin levels was lower in case of PAA in comparison to alginate.
      Scaffold degradation in histopathological specimens was visible. CONCLUSION: The
      results indicate that PAA implants undergo biodegradation and nonspecific
      inflammatory response is comparable to alginate.

PMID- 18810985
TI  - [Comparison of growth of the follicle and mesenchymal stem cells to urothelial
      cells and fibroblasts on collagen scaffold].
AB  - To develop a tissue-engineered bladder wall replacement with elements obtained
      from non-urinary tract components is an atractive idea. The aim of this study was
      to compare growth of hair follicles epithelial stem cells and mesenchymal stem
      cells to urothelial cells and fibroblasts cells on scaffold prepared from rat
      collagen type I. MATERIALS AND METHODS: Wistar rats were used in experiment. Rat
      urothelial cells, hair follicles epithelial stem cells, mesenchymal stem cells
      and 3T3 cells were cultivated in DMEM (Sigma) supplemented with 10% (or 20% for
      hair follicles cells) of Fetal Bovine Serum (FBS). Epithelial cell cultures were
      suplemented with EGF (10 ng/ml; Sigma). Cells were stained using anti
      cytokeratine (Clone MMF) and anti-cytokeratine 7. Anti-CD34 and anti-p63 staining
      were done. Collagen scaffold was prepared from tendoms of Wistar rat's tails. 6
      well plates were covered with collagen scaffold. 25 x 10(3) of cells were seeded
      on each well and cultured for a week. Cells in the controls were seeded on
      polystyrene surface. After a week cell viability was assessed using MTT test
      (Sigma). Each experiment was triplicated. Photo documentation was prepared. The
      differences between means were compared using t-Student test. RESULTS: There were
      106.5 +/- 23.4 x 10(3) and 310.7 +/- 60.7 x 10(3) of 3T3 fibroblasts growing on
      polystyrene and collagen, respectively (p < 0.05). The initial cell number was
      25.0 x 10(3). Urothelial cells expressed epithelial markers. There were 40.0 +/-
      4.2 x 10(3) and 4.5 +/- 1.8 x 10(3) urothelial cells growing on polystyrene and
      collagen, respectively after 7 days of culture (p < 0.01). There were 118.5 +/-
      19.7 x 10(3) and 114.1 +/- 33.2 x 0(3) of mesenchymal stem cells growing on
      polystyrene and collagen, respectively (NS). Hair follicles epithelial cells
      expressed epithelial markers and were slightly positive for CD34 and p63. There
      were 292.5 +/- 33.3 x 10(3) and 167.4 +/- 24.9 x 10(3) of hair follicles
      epithelial cells growing on polystyrene and collagen, respectively (p < 0.05).
      Collagen scaffold decreased proliferation of follicle epithelial and urothelial
      cells. CONCLUSIONS: Hair follicles epithelial stem cells and mesenchymal stem
      cells can be potentially used in tissue-engineering, with the guarantee of the
      sufficient cell number for transplantation. It seems that construction in vitro
      of urinary bladder walls from elements obtained from non-urinary tract tissues is
      feasible.

PMID- 18810986
TI  - [The influence of lysozyme dimmer on chosen parameters of blood in healthy
      rabbits].
AB  - The natural compounds which affect defensive mechanisms of organism are important
      in prophylaxis and therapy of diseases in human and animals. Lysozyme is an
      enzyme which originates from chicken egg proteins. It modulates non-specific and
      humoral immunological mechanisms. A higher bioactivity has a lysozyme dimmer. The
      aim of study was assessment of influence of the lysozyme dimmer on chosen blood
      parameters, morphology and functions of internal organs and healing processes of
      experimental wounds in rabbits. Lysozyme dimmer (KLP-602) was used obtained
      process polymerisations enzyme lyzosyme from chicken egg white. The experimental
      group were on New Zealand White rabbits. Systemic reactions were investigated in
      animals after two injections of lysozyme dimer in dose 0,02 mg/kg b.w. during 21
      days. Blood was collected before and after administration of lysozyme dimer in 4,
      6, 24 h and in 3, 7, 21 day after first and in 4, 24 h and 3, 7 day after second
      injection. The following parameters were evaluated of red blood cells number
      (RBC), hemoglobin concentration (HGB), haematocrit value (HCT), red blood cell
      indices (MCV, MCH, MCHC), white blood cells number (WBC) and leukogram. Total
      serum proteins, components C3 and C4 of complement, immunoglobulins G and M,
      concentration were determined in the serum. Activated partial thromboplastin time
      (APTT), prothrombin time (PT) and fibrinogen concentration were evaluated in the
      plasma. Simultaneously, the activity of alkaline phosphatate, GPT and GOT were
      assessed. Administration rabbits with lysozyme dimmer caused slight decrease in
      RBC number, Hb concentration, HCT and the neutrophils percentage and increase in
      the lymphocytes percentage. The concentrations of TSP, immunoglobulins, the
      components of complement ware increased too. APTT an PT were normal but the
      fibrinogen concentration was increased. The activity of GOT and GPT were
      unchanged. Changes are in range of value normal and step out more quickly after
      two injection than after firste injection. The morphology of organs (liver,
      lungs, heart and kidneys) was normal.

PMID- 18810987
TI  - Chemical and pharmacological investigations of Metaxya rostrata.
AB  - In a bioassay-guided approach the chemical composition of rhizomes of Metaxya
      rostrata (Kunth C. Presl) was studied for the first time. Investigations of the
      cytotoxicity of extracts and fractions on SW480 colorectal carcinoma cells
      resulted in the isolation of two polyphenols--cinnamtannin B-1 and aesculitannin
      B. The structures of the compounds were elucidated by different NMR experiments.
      Additionally, sugars, common sterols, such as sitosterol, stigmasterol and
      campesterol, as well as chlorogenic acid and caffeic acid were identified in
      Metaxya rostrata.

PMID- 18810988
TI  - Evaluation of antioxidant activity of some common mosses.
AB  - The antioxidant activity of ethanol extracts of Atrichum undulatum, Polytrichum
      formosum (Polytrichaceae), Pleurozium schreberi (Entodontaceae) and Thuidium
      tamariscinum (Thuidiaceae) was evaluated by an electrochemical method (cyclic
      voltammetry) and standard photometric methods: Fe(III) to Fe(II) reducing power,
      nitric oxide scavenging (NO) assay and simulation of Fenton-type reaction by
      nonsite-specific (NSSOH) and site-specific (SSOH) hydroxyl radical-mediated 2
      deoxy-D-ribose degradation inhibition. The total content of phenols was
      determined by the Folin-Ciocalteau reagent. All tested species showed antioxidant
      effects lower than the positive control, caffeic acid. The extracts of A.
      undulatum and P. formosum contained the highest content of phenols and were the
      most effective in Fe(III) to Fe(II) reducing power, cyclic voltammetry and SSOH
      assay. By contrast, only the extract of Pl. schreberi showed activity in the
      NSSOH assay. A. undulatum and T. tamariscinum extracts were the most active in
      the NO assay. The results suggest that the extracts of A. undulatum and P.
      formosum possess stronger antioxidant activity than those of Pl. scheberi and T.
      tamariscinum, but they affect the Fenton-type reaction mainly by iron chelation.

PMID- 18810989
TI  - Non-phenolic antioxidant compounds from Buddleja asiatica.
AB  - The methanol extract of the leaves of Buddleja asiatica Lour. (Loganiaceae)
      showed antioxidant activity toward the well known in vitro antioxidant tests such
      as total antioxidant capacity by the phosphomolybdenum method, free radical
      scavenging activity by the 1,1-diphenyl-2-picrylhydrazyl scavenging assay (DPPH
      assay) and hydrogen peroxide scavenging methods. Due to the high scavenging
      activity of the n-butanol successive fraction toward DPPH and H2O2 (SC50 = 11.99
      and 18.54 microg/ml, respectively), this extract was subjected to chromatographic
      separation and isolation. Four non-phenolic compounds were isolated and
      identified on the basis of spectroscopic and chemical analyses: 1-O-beta-D
      glucopyranosyl-2-methoxy-3-(2-hydroxy-triaconta-3,12-dienoate)-glycerol (1), 3-O
      [alpha-L-rhamnopyranosyl-(1-->4)-beta-D-glucopyranosyl-(1-->3)]-[beta-D
      glucopyranosyl-(1-->2)]-beta-D-fucopyranosyl-olean-11,13(18)-diene-3 beta,23,28
      triol (2), 3-O-[alpha-L-rhamnopyranosyl-(1-->4)-beta-D-glucopyranosyl-(1-->4)
      beta-D-glucopyranosyl-(1-->3)]-beta-D-fucopyranosyl-olean-11,13(18)-diene-3,23,28
      triol (3), and 3-O-[alpha-L-rhamnopyranosyl-(1-->4)-beta-D-glucopyranosyl-(1-
      >3)]-[beta-D-xylopyranosyl-(1-->2)]-beta-D-glucuronopyranosyl-acid-olean
      11,13(18)-diene-3 beta,23,28-triol (4). The four compounds were evaluated as
      antioxidant agents using the three antioxidant bioassay tests.

PMID- 18810990
TI  - Active metabolites from Dunalia spinosa resinous exudates.
AB  - Dunalia spinosa, a plant used in folk medicine for toothaches, breathing problems
      and cleansing wounds, was found active as antimicrobial and antioxidant. A new
      (E)-aurone rutinoside (dunaurone) has been isolated from the aerial parts of the
      plant, and its structure was determined by spectroscopic means. Lupeol, beta
      sitosterol, scopoletin, quercetin and withaferin A were also found. All the
      extracts exhibited strong antimicrobial activity while dunaurone showed only weak
      antimicrobial inhibition against Klebsiella pneumoniae; in addition it presented
      a significant free radical scavenging activity.

PMID- 18810991
TI  - Antileishmanial, antimalarial and antimicrobial activities of the extract and
      isolated compounds from Austroplenckia populnea (Celastraceae).
AB  - Austroplenckia populnea (Celastraceae), known as "marmelinho do campo", is used
      in Brazilian folk medicine as antimicrobial, anti-inflammatory, and antitumoural
      agent. The aim of the present work was to evaluate the antimicrobial,
      antileishmanial and antimalarial activities of the crude hydroalcoholic extract
      of A. populnea (CHE) and some of its isolated compounds. The phytochemical study
      of the CHE was carried out affording the isolation of methyl populnoate (1),
      populnoic acid (2), and stigmast-5-en-3-O-beta-(D-glucopyranoside) (3). This is
      the first time that the presence of compound 3 in A. populnea is reported. The
      results showed that the CHE presents antifungal and antibacterial activities,
      especially against Candida glabrata and Candida albicans, for which the CHE
      showed IC50 values of 0.7 microg mL(-1) and 5.5 microg mL(-1), respectively,
      while amphotericin B showed an IC50 value of 0.1 microg mL(-1) against both
      microorganisms. Compounds 1-3 were inactive against all tested microorganisms. In
      the antileishmanial activity test against Leishmania donovani, the CHE showed an
      IC50 value of 52 microg mL(-1), while compounds 2 and 3 displayed an IC50 value
      of 18 microg mL(-1) In the antimalarial assay against Plasmodium falciparum (D6
      and W2 clones), it was observed that all evaluated samples were inactive. In
      order to compare the effect on the parasites with the toxicity to mammalian
      cells, the cytotoxicity activity of the isolated compounds was evaluated against
      Vero cells, showing that all evaluated samples exhibited no cytotoxicity at the
      maximum dose tested.

PMID- 18810992
TI  - Fumigant antifungal activity of essential oil components from Acorus gramineus
      against three phytopathogenic fungi.
AB  - Analysis by gas chromatography-mass spectrometry led to the identification of 26
      compounds in Acorus gramineus essential oil. The antifungal activity of the
      identified compounds was tested singularly by using standard compounds. Allyl
      isothiocyanate and cis-asarone showed inhibition rates of 100% against P.
      cactorum at 28 mg/l air. In a test with C. parasitica and E. circinatum, allyl
      isothiocyante and cis-asarone showed moderate activity at 28 mg/l air.

PMID- 18810993
TI  - Antineoplastic 31-norcycloartanones from Solanum cernuum vell.
AB  - Triterpenoids with 31-norcycloartanone structure were isolated for the first time
      from the Solanum genus. Cycloeucalenone and 24-oxo-31-norcycloartanone were the
      main constituents of the dichloromethane extract of Solanum cernuum Vell. leaves
      [7% (w/w) and 1.47% (w/w)]. Both triterpenoids were tested against human tumour
      cell lines, and 24-oxo-31-norcycloartanone was significantly active and selective
      against the lung tumour cell line NCI-H460 with total growth inhibition at 1.10
      microg/mL, growth inhibition 50 at 0.19 microg/mL and lethal concentration 50 at
      8.43 microg/mL, while cycloeucalenone showed poor activity. A homologous series
      of alkanes (C25-C34), beta-sitosterol, and the xanthophyll lutein were also
      identified. The antiulcer activity was assayed for the dichloromethane extract.
      In the gastric ulcer model induced by 95% ethanol, administration of 500, 1000
      and 2000 mg/kg/po dichloromethane extract gave ulcer lesion indices of,
      respectively, 38.2, 61.0 and 81.9%, while carbenoxolone inhibited 88.9% at 200
      mg/kg. In the gastric ulcer model induced by indomethacin the dichloromethane
      extract showed a small percentage of lesion inhibition. The ethanol extract was
      also analyzed and was mainly composed of glycoalkaloids, peptides and
      disaccharides.

PMID- 18810994
TI  - Cytotoxic beta-dihydroagarofuran sesquiterpenoids from the fruits of Celastrus
      orbiculatus.
AB  - Assay-guided fractionation led to the isolation of nine beta-dihydroagarofuran
      sesquiterpenoids from the fruits of Celastrus orbiculatus. All isolated beta
      dihydroagarofuran sesquiterpenoids were tested for their cytotoxic activity
      against human melanoma A375-S2 and human cervical carcinoma Hela cell lines.
      Among them, compounds 1-5 and 7 showed cytotoxic activity. Compound 3 exhibited
      promising cytotoxicity against both human melanoma A375-S2 and human cervical
      carcinoma Hela cell lines. The structure-activity relationship was discussed
      briefly.

PMID- 18810995
TI  - Cytotoxicity of nitroaromatic explosives and their biodegradation products in
      mice splenocytes: implications for their immunotoxicity.
AB  - Nitroaromatic explosives like 2,4,6-trinitrotoluene (TNT) and 2,4,6
      trinitrophenyl-N-methyl-nitramine (tetryl) comprise an important group of toxic
      environmental pollutants, whose toxicity is mainly attributed to the flavoenzyme
      electrontransferase-catalyzed redox cycling of their free radicals (oxidative
      stress) and DT-diaphorase [NAD(P)H:quinone oxidoreductase, NQO1, EC 1. 6.99.2]
      catalyzed formation of alkylating nitroso and/or hydroxylamine metabolites.
      Because of the incomprehensive data on the immunotoxic effects of nitroaromatic
      explosives, we have studied the structure-cytotoxicity relationships in the
      action of tetryl, TNT as well as its amino and hydroxylamino metabolites, and
      related nitroaromatic compounds towards mouse splenocyte cells. The protective
      effects of desferrioxamine and the antioxidant N,N'-diphenyl-p-phenylene diamine
      against the cytotoxicity of TNT and other nitroaromatics showed that the
      oxidative stress-type cytotoxicity mechanism takes place. In addition, the
      cytotoxicity of nitroaromatics is also partly prevented by an inhibitor of NQO1,
      dicumarol. The cytotoxicity of the amino metabolites of TNT is also partly
      prevented by alpha-naphthoflavone and isoniazide, which points to the involvement
      of cytochromes P-450 in their activation. In general the cytotoxicity of
      nitroaromatics in splenocytes increases with an increase in their single-electron
      reduction potential, E1(7). This points to the prevailing mechanism of the
      oxidative stress-type cytotoxicity. The obtained structure-activity relationship
      and the studies of other mammalian cell lines showed that the immunotoxic
      potential of nitroaromatic explosives may decrease in the order tetryl > or = TNT
      > or = hydroxylamino metabolites of TNT > amino and diamino metabolites of TNT.

PMID- 18810996
TI  - Inhibitory effect of some acetyl esters and acetamides on glycation of the
      histone H1.
AB  - Non-enzymatic glycosylation (glycation) is a spontaneous set of reactions between
      reducing sugars and free amino groups in proteins or other biomolecules leading
      to the formation of fluorescent and coloured compounds known as advanced
      glycation end products (AGEs). AGEs cause structural changes of key proteins in
      humans, and therefore they are related with a number of physiological processes
      and diseases such as aging, atherosclerosis, cataract, arthritis, Alzheimer's
      disease. Two main strategies have been employed to prevent the formation of AGEs:
      a) low carbohydrate diet and b) pharmacological intervention. The latter includes
      treatment with reactive compounds which might be either sugar competitors (type
      A), carbonyl traps (type B) or free radical trapping antioxidants (type C).
      Acetylsalicylic acid (ASA, aspirin) is a good example of sugar competitor capable
      of inhibiting glycation by acetylating epsilon-amino groups of lysine residues in
      proteins. Taking into consideration the inhibiting effect of ASA on glycation we
      designed to study the antiglycation activity of other acetyl group-containing
      compounds (acetamides and acetyl esters) using the lysine-rich protein histone H1
      as a model. The glycation of the histone H1 was carried out by either fructose or
      a complex mixture of glycating agents obtained from E. coli and monitored by
      fluorescent spectroscopy, SDS-PAGE and measurement of the content of reactive
      carbonyl groups in the target protein. Our results showed that the inhibitory
      effect of phenyl acetate, acetanilide, 4-acetamidophenylacetic acid and
      isopropenyl acetate was comparable to that of ASA. Based on the obtained results
      we conclude that these compounds act as free radical scavengers protecting
      proteins from the damaging effect of reactive oxygen species produced during the
      formation of AGEs.

PMID- 18810997
TI  - Further sesquiterpene lactones from Viguiera robusta and the potential anti
      inflammatory activity of a heliangolide: inhibition of human neutrophil elastase
      release.
AB  - In addition to known heliangolides, a new eudesmanolide was isolated from the
      leaf rinse extract of Viguiera robusta (Asteraceae). Structural elucidation was
      based on spectral analysis. It is the first report on eudesmanolides in members
      of the subgenus Calanticaria of Viguiera. In this work, the main isolated
      compound, the furanoheliangolide budlein A, besides its previously reported in
      vitro and in vivo anti-inflammatory activities, inhibited human neutrophil
      elastase release. The inhibition was at the concentration of (16.83 +/- 1.96)
      microM for formylated bacterial tripeptide (fMLP) stimulation and (11.84 +/-
      1.62) microM for platelet aggregation factor (PAF) stimulation, being slightly
      less active than the reference drug parthenolide. The results are important to
      demonstrate the potential anti-inflammatory activities of sesquiterpene lactones
      and corroborate the previous studies using other targets.

PMID- 18810998
TI  - Evaluation of lipoxygenase inhibitory activity of anacardic acids.
AB  - 6-Alkylsalicylic acids inhibit the linoleic acid peroxidation catalyzed by
      soybean lipoxygenase-1 (EC 1.13.11.12, type 1) competitively and without pro
      oxidant effects. This activity is largely dependent on the nature of their alkyl
      side chains. Inhibitory activities of anacardic acids, viz. 6
      pentadec(en)ylsalicylic acids, isolated from the cashew Anacardium occidentale,
      were initially used for comparison because their aromatic head portions are the
      same. Consequently, the data should be interpreted to mean that changes in the
      hydrophobic side chain tail portions of the molecules evaluated correlate with
      the specific activity determined.

PMID- 18810999
TI  - Activity of essential oils and individual components against acetyl- and
      butyrylcholinesterase.
AB  - We have tested acetylcholinesterase (AChE) and butyrylcholinesterase (BChE)
      inhibitory activities of nineteen essential oils obtained from cultivated plants,
      namely one from Anethum graveolens L. (organic fertilizer), two from Foeniculum
      vulgare Mill. collected at fully-mature and flowering stages (organic
      fertilizer), two from Melissa officinalis L. (cultivated using organic and
      chemical fertilizers), two from Mentha piperita L. and M. spicata L. (organic
      fertilizer), two from Lavandula officinalis Chaix ex Villars (cultivated using
      organic and chemical fertilizers), two from Ocimum basilicum L. (green and purple
      leaf varieties cultivated using only organic fertilizer), four from Origanum
      onites L., O. vulgare L., O. munitiflorum Hausskn., and O. majorana L.
      (cultivated using organic fertilizer), two from Salvia sclarea L. (organic and
      chemical fertilizers), one from S. officinalis L. (organic fertilizer), and one
      from Satureja cuneifolia Ten. (organic fertilizer) by a spectrophotometric method
      of Ellman using ELISA microplate-reader at 1 mg/ml concentration. In addition, a
      number of single components widely encountered in most of the essential oils
      [gamma-terpinene, 4-allyl anisole, (-)-carvone, dihydrocarvone, (-)-phencone,
      cuminyl alcohol, cumol, 4-isopropyl benzaldehyde, trans-anethole, camphene, iso
      borneol, (-)-borneol, L-bornyl acetate, 2-decanol, 2-heptanol, methyl-heptanol,
      farnesol, nerol, iso-pulegol, 1,8-cineole, citral, citronellal, citronellol,
      geraniol, linalool, alpha-pinene, beta-pinene, piperitone, iso-menthone,
      menthofurane, linalyl oxide, linalyl ester, geranyl ester, carvacrol, thymol,
      menthol, vanilline, and eugenol] was also screened for the same activity in the
      same manner. Almost all of the essential oils showed a very high inhibitory
      activity (over 80%) against both enzymes, whereas the single components were not
      as active as the essential oils.

PMID- 18811000
TI  - The role of aspterric acid in auxin-regulated reproductive growth of Arabidopsis
      thaliana.
AB  - Application of 100 microM aspterric acid (AA), a pollen growth inhibitor, with
      different concentrations of indole-3-acetic acid (IAA) results in the recovery of
      normal pollen development of Arabidopsis thaliana. Treatment with 100 microM AA
      plus 5 mM IAA significantly induced the normal seed production. Treatment with
      100 microM N-1-naphthylphthalamic acid (NPA), a polar auxin transport inhibitor,
      did not reduce the pollen growth but inhibited seed production. 100 microM NPA
      plus 5 mM IAA did not induce any seed production. The endogenous level of IAA in
      stems and leaves of A. thaliana treated with 100 microM AA was similar to that of
      the untreated control. In contrast to AA treatment, the IAA level by the
      treatment with 100 microM NPA was about twice as much as that of the untreated
      control. These results suggest that AA affects the Arabidopsis reproductive
      growth without inhibiting IAA biosynthesis and transport.

PMID- 18811001
TI  - Glycosylation of xanthohumol by fungi.
AB  - A screening test on 29 microorganisms for transformation of xanthohumol led to
      the selection of twelve fungal strains. One of them, Beauveria bassiana AM278,
      converted xanthohumol into a glucosylated derivative. This product was identified
      as xanthohumol 4'-O-beta-D-4'''-methoxyglucopyranoside.

PMID- 18811002
TI  - Biotransformation of glabratephrin, a rare type of isoprenylated flavonoids, by
      Aspergillus niger.
AB  - Microbial transformation of glabratephrin, the major isolated compound from
      Tephrosia purpurea, afforded pseudosemiglabrin. The formation of the transformed
      compound seems to be performed via ring opening-closure of a five-membered ring
      causing transformation from a spiro into a fused system. The structure of the
      transformed compound was determined by comprehensive NMR studies, including DEPT,
      COSY, HMQC, NOE and MS.

PMID- 18811003
TI  - Biosynthetic origin of graphenone in cultured lichen mycobionts of Graphis
      handelii.
AB  - The biosynthetic origins of the carbon skeleton in graphenone were verified by
      feeding the culture of spore-derived mycobionts of the lichen Graphis handelii
      with sodium [1-13C]-acetate, sodium [1,2-13C2]-acetate, sodium [2-13C]-pyruvate,
      [1,2,3-13C]-glycerol, [13CH3]-methionine and sodium [1,4-13C2]-succinate.

PMID- 18811004
TI  - Changes of antioxidant enzyme and phenylalanine ammonia-lyase activities during
      Chimonanthus praecox seed maturation.
AB  - Changes in peroxidase (POD), superoxide dismutase (SOD), catalase (CAT) and
      phenylalanine ammonia-lyase (PAL) activities were studied during Chimonanthus
      praecox seed maturation. According to our findings the protein content increased
      steadily from 8 to 12 weeks after flowering, and thereafter decreased
      significantly. Similarly, SOD and POD activities increased gradually up to 12
      weeks after flowering and then declined. PAL activity declined gradually during
      seed maturation. CAT activity, however, showed no changes during seed maturation.
      By means of polyacrylamide gel electrophoresis (PAGE), SOD and POD isoenzymes
      were observed during seed maturation. The staining intensities of SOD and POD
      isoenzymes correlated well with SOD and POD activities as obtained by an assay in
      solution. These findings suggest that POD, SOD and PAL may be involved in the
      growth and development during Chimonanthus praecox seed maturation.

PMID- 18811005
TI  - Quantification of mRNAs and housekeeping gene selection for quantitative real
      time RT-PCR normalization in European beech (Fagus sylvatica L.) during abiotic
      and biotic stress.
AB  - Analyses of different plant stressors are often based on gene expression studies.
      Quantitative real-time RT-PCR (qRT-PCR) is the most sensitive method for the
      detection of low abundance transcripts. However, a critical point to note is the
      selection of housekeeping genes as an internal control. Many so-called
      'housekeeping genes' are often affected by different stress factors and may not
      be suitable for use as an internal reference. We tested six housekeeping genes of
      European beech by qRT-PCR using the Sybr Green PCR kit. Specific primers were
      designed for 18S rRNA, actin, glyceraldehyde-3-phosphate dehydrogenase (GAPDH1,
      GAPDH2), a-tubulin, and ubiquitin-like protein. Beech saplings were treated with
      increased concentrations of either ozone or CO2. In parallel, the expression of
      these genes was analyzed upon pathogen infection with Phytophthora citricola. To
      test the applicability of these genes as internal controls under realistic
      outdoor conditions, sun and shade leaves of 60-year-old trees were used for
      comparison. The regulation of all genes was tested using a linear mixed-effect
      model of the R-system. Results from independent experiments showed that the only
      gene not affected by any treatment was actin. The expression of the other
      housekeeping genes varied more or less with the degree of stress applied. These
      results highlight the importance of undergoing an individual selection of
      internal control genes for different experimental conditions.

PMID- 18811006
TI  - PSII photochemistry and antioxidant responses of a chickpea variety exposed to
      drought.
AB  - The effect of drought on the chickpea variety ILC 3279 was investigated at the
      vegetative stage. After 20 days from sowing, the plants subjected to drought
      stress for 3, 5 and 7 days imposed by withholding water were permitted to recover
      by rewatering for 2 days after 3, 5 and 7 days of drought. Shoot elongation, leaf
      production, fresh and dry biomass reduced while MDA and proline accumulation
      increased with extended duration of stress. The plants stressed for 3 days
      exhibited a rapid drop in their relative and absolute water contents. The quantum
      efficiency of PSII open centres in the dark-adapted and light-saturated state,
      excitation energy trapping of PSII and electron transport rate decreased
      significantly from the 5th day to the end of the drought treatments. Plants
      drought-stressed for 7 days brought about a marked increase in non-photochemical
      energy dissipation and a marked decline in photochemical quenching. After
      rewatering all chlorophyll a fluorescence characteristics except for F(M)
      completely recovered and reached the control values. Under 5 and 7 days of
      drought, the anthocyanin content increased gradually while the total chlorophyll
      content of leaves declined compared to the controls. The total carotenoid content
      remained unchanged during the experiments. The antioxidant enzyme response to
      drought treatments was quite variable. The total SOD activity upregulated with
      increasing duration of stress. On the other hand, the total APX activity was
      significantly higher only on the 7th day while the total POD activity increased
      from the 5th day. Differences in the total GR activity of treated groups were not
      statistically significant compared to their controls throughout the treatments.
      The present results indicate that the chickpea variety ILC 3279 withstands severe
      drought with its upregulated protective mechanisms at the vegetative stage.

PMID- 18811007
TI  - Rapid and high quality DNA isolation from Origanum onites for RAPD and ISSR
      analysis.
AB  - Origanum onites is an economically important medicinal plant with high essential
      oil content. Lack of an appropriate DNA isolation procedure is a limiting factor
      for any molecular study of this plant. We have used a protocol for genomic DNA
      isolation based on a hexadecyltrimethylammonium bromide (CTAB) method described
      for other plant species. The method involves mortar grinding of leaf tissue,
      modified CTAB extraction using high salt concentrations and polyvinyl
      pyrrolidone, and successive isoamyl alcohol/chloroform extractions. The yield was
      approx. 20 microg DNA per 200 mg of initial fresh plant material. The genomic DNA
      obtained by this method was suitable to be used in restriction digests, inter
      simple sequence repeat (ISSR) and randomly amplified polymorphic DNA (RAPD)
      reactions. This extraction method should facilitate the molecular analysis of
      Origanum chemotypes.

PMID- 18811008
TI  - Microtitre plate assay for biofilm formation, production and utilization of
      hydroxybiphenyl by Rhodococcus sp. isolated from gasoline-contaminated soil.
AB  - Gasoline-contaminated soil from Isfahan, Iran was selected to isolate a bacterium
      capable of desulfurizing dibenzothiophene (DBT). The isolated strain was named R1
      and identified as Rhodococcus erythropolis through biochemical tests as well as
      sequencing of 16S rRNA gene. This strain could efficiently produce 2
      hydroxybiphenyl (HBP) from DBT via the 4S metabolic pathway. The highest HBP
      amount was produced at 2 mM DBT with addition of glucose (10 g l(-1)), ethanol (3
      g l(-1)), glycerol (2 g l(-1)) or succinate (10 g l(-1)) as carbon sources at pH
      7. Highest respiration and growth rates were observed by microplate titration on
      0.1 mM HBP, and addition of 0.2 mM HBP to glucose (1 g l(-1)) and DBT (0.3 mM)
      could inhibite the respiration of the isolate. The isolated strain could grow up
      to 0.4 mM of HBP when it is used with mineral sulfur as sole sulfur source. To
      the best of our knowledge this is the first report on a microtiter assay for the
      production and utilization of HBP by Rhodococcus.

PMID- 18811009
TI  - Decreased DNA repair capacity of UV-irradiated cells following interferon
      treatment.
AB  - The aim of this study was to examine the effect of interferons (IFNs) on the
      recovery of UV-damaged cells by means of measuring cell viability rates. The
      influence of the recombinant human interferons IFN-alpha, IFN-beta and IFN-gamma
      on the repair capacity of the UV-irradiated human cell lines WISH and HeLa was
      studied. The ability of cells to repair UV-induced damage was determined by the
      comet assay and both short- and long-term survival assays in proliferating cell
      cultures. We found that INFs negatively regulated DNA repair in cells damaged by
      UV light. One day after treatment, in both cell lines tested, IFN-alpha had a
      stronger inhibitory effect than IFN-gamma. Combined treatment with different IFNs
      exhibited a stronger inhibitory effect on cell recovery than treatment with each
      of them. The protein kinase inhibitor wortmanin further aggravated the effect of
      IFNs on cell survival.

PMID- 18811010
TI  - Optimization of fluorophore-assisted carbohydrate electrophoresis.
AB  - Fluorophore-assisted carbohydrate electrophoresis (FACE) is a simple and
      inexpensive method for separating saccharides. Oligosaccharides were tagged with
      the charged fluorophore 8-aminonaphthalene-1,3,6-trisulfonate (ANTS), and the
      reductive amination reactions were essentially complete after approximately 16 h
      under the given experimental conditions. Saccharide-ANTS adducts were then
      separated by electrophoresis on 32% C(ACR)/2.4% C(BIS) polyacrylamide gel at
      alkaline pH. This technique doesn't require sophisticated instrumentation and
      highly trained personnel.

PMID- 18811011
TI  - Kairomone attractant for the leafmining fly, Liriomyza bryoniae (Diptera,
      Agromyzidae).
AB  - A field test carried out in an industrial greenhouse in Lithuania revealed the
      attractiveness of synthetic methyl salicylate (MeSa) towards an economically
      important leafmining tomato pest, Liriomyza bryoniae (Kaltenbach) (Diptera,
      Agromyzidae). The behavioural reaction of the flies depended very much on the
      simultaneous presence of both olfactory and visual stimuli. The attractiveness
      depended on the colour of a sticky trap: MeSa attracted significantly more flies
      (ca. 2.2 times) when placed in yellow traps than in aluminium foil colour ones,
      when catches in such traps were compared to a corresponding control. L. bryoniae
      is the first species within the Agromyzidae family attracted by MeSa. The
      attractant was attributed to kairomones, as the compound is known as a plant
      produced volatile. MeSa can be an effective extra-tool for increasing the
      attractiveness of traps. It should be evaluated in future whether such trap/bait
      combination is effective for the mass trapping of L. bryoniae leafminers in
      greenhouses (closed area).

PMID- 18811012
TI  - Egg white, a favourable solvent to extract the active ingredient of Mylabris
      phalerata.
AB  - To characterize the role of hen eggs used for analyzing the insect Mylabris
      phalerata a traditional Chinese medicine for curing liver cancer, egg white was
      separated from the whole egg and added to M. phalerata. The volatile compounds
      found in egg white when added to M. phalerata and therefore in M. phalerata
      itself were analyzed by GC. Cantharidin was detected both in egg white added to
      M. phalerata and M. phalerata itself. Egg white can be used as a favourable
      solvent for extracting the active ingredient of M. phalerata.

PMID- 18811013
TI  - Diterpenoid production in hairy root culture of Salvia sclarea L.
AB  - Growth and diterpenoid accumulation (salvipisone, ferruginol, aethiopinone and 1
      oxoaethiopinone) during the growth cycle of a Salvia sclarea hairy root culture
      are described. The roots transformed by Agrobacterium rhizogenes (LBA 9402) were
      cultured in half-strength B5 liquid medium supplemented with 30 g L(-1) sucrose
      under light (16 h/8 h light/dark). A culture period of 30 days was optimal for
      both biomass and diterpenoid production. The total content of four diterpenoids
      in the hairy roots [(27.3 +/- 0.6) mg g(-1) dry weight] was higher than that of
      roots of field-grown S. sclarea plants [(3.15 +/- 0.15) mg g(-1) dry weight]. In
      transformed roots, aethiopinone was the main diterpenoid, whereas the principal
      diterpenoid of natural roots was salvipisone.

PMID- 18811014
TI  - Subtle signs. The little stuff is the big stuff.

PMID- 18811015
TI  - Do you care enough to ICARE? Distilling the essence of the practice of EMS.

PMID- 18811016
TI  - Needle in a racetrack. Crews must scour the muck after a driver hits a chain-link
      fence.

PMID- 18811017
TI  - Equal opportunity threat. A female patient with a concealed weapon takes EMS by
      surprise.

PMID- 18811018
TI  - The care and feeding of firefighters.

PMID- 18811019
TI  - Military leadership. Can its seven core values work for EMS?
AB  - Every EMS agency has a boss like it: dominating and opinionated, immaculately
      attired and groomed, with close-cropped hair and an abrupt personality. They are
      hard to understand and even harder to like. They demand respect and are quick to
      lash out when angered. They demand obedience because "Lives are at stake!"
      Sometimes they really are veterans of our nation's military, sometimes they
      aren't. But what they all have in common is a misinterpretation of what "military
      leadership" really is. The basic misconception of military leadership is that the
      military demands absolute, unrelenting subservience to the commands of one's
      superior, that leadership is best done harshly, and that there is no room for
      error. Yet nothing could be further from the truth.

PMID- 18811020
TI  - Beyond the basics: acute abdominal pain.
AB  - Acute abdominal pain is a common presenting complaint encountered by prehospital
      care personnel. It can be an indication of a number of diseases and conditions
      involving abdominal organs and structures or associated with referred pain from
      organs and structures outside the borders of the abdominal cavity. However, a
      sudden onset and severe abdominal pain is almost always caused by some type of
      intra-abdominal pathology.

PMID- 18811021
TI  - Advanced clinical insights & practice: acute coronary syndrome.
AB  - This article provides the critical care paramedic with a review of the ongoing
      management of a patient with an acute coronary syndrome (ACS). In the March
      issue, we focused on the management and critical care transport of an unstable
      ACS patient from a small outlying community hospital back to the cath lab. In
      this article, we focus on the same patient as she progresses through the
      catheterization lab with complications. It is important to remember that, due to
      the instability of the precipitating condition, not all patients have a
      successful outcome with catheterization, and the critical care transport crew may
      be summoned again for transport.

PMID- 18811022
TI  - EMS innovations 2008. Clinical and operational excellance in prehospital care.

PMID- 18811023
TI  - Familial pseudarthrosis of the clavicle: does it need treatment?
AB  - The eighth family with multiple cases of congenital pseudarthrosis of the
      clavicle is described. This usually presents as a clavicular lump and is distinct
      from more common conditions such as birth fractures, craniocleidal dysostosis and
      neurofibromatosis. There has so far been no clear indication on whether familial
      pseudarthrosis of the clavicle should be treated operatively. We recommend that
      when a suspected case of congenital pseudarthrosis of the clavicle is diagnosed
      the parents and siblings be examined also. If other family members are affected,
      we advise that the treatment should be conservative.

PMID- 18811024
TI  - Surgical treatment of acute and chronic acromioclavicular dislocation Tossy type
      III and V using the Hook plate.
AB  - We treated 16 patients with acute and chronic acromioclavicular dislocations type
      III and V by open reduction and fixation using a Hook plate (AO). Plate removal
      was performed 7 months later on average (range 3 1/2 - 13). A clinical and
      radiological follow-up was performed after a mean time interval of 29 months
      (range, 11-40) from the date of plate removal. The L'Insalata scoring system was
      used to compare the function of the injured shoulder before operation and after
      removal of the hook plate. Constant's score was used to evaluate the operated
      shoulder after the removal of the hook plate. Complications were limited and the
      overall results were excellent.

PMID- 18811025
TI  - Custom-made endoprosthetic reconstruction of the distal humerus for non-tumorous
      pathology.
AB  - Eight patients underwent custom-made endoprosthetic elbow reconstruction between
      1989 and 2006 either for failed primary total elbow replacements or following
      complex fracture complications. A functional assessment using the Toronto
      Extremity Salvage (TES) score was performed. Patients were followed for a mean of
      46.1 months (range : 25 to 88). One patient who presented with an infected
      periprosthetic fracture around a total elbow replacement, failed two-stage
      reconstruction and underwent excision arthroplasty. The remaining seven patients
      were available for functional follow-up. Average flexion deformity was 15 degrees
      (range: 7 to 35) and average flexion arc was 85 degrees (range : 70 to 130). The
      mean TES score was 67.3 (range: 36.6 to 95.9). Custom made endoprosthetic
      reconstruction allowed for a satisfactory outcome in all but one of these eight
      patients with severe bony destruction around the elbow in the absence of tumour
      infiltration.

PMID- 18811026
TI  - Proximal row carpectomy: a volar approach.
AB  - We retrospectively evaluated 14 patients who underwent proximal row carpectomy
      through a volar, instead of the routine dorsal approach. The patients were
      screened for range of motion, grip strength, VAS pain score, and responded to a
      DASH questionnaire. At a mean follow-up of 16 months, range of motion and grip
      strength were satisfactory. The disability score was improved, however the pain
      score was slightly higher than the preoperative score. We conclude that proximal
      row carpectomy through a volar approach gives comparable results to those
      reported with the dorsal approach.

PMID- 18811027
TI  - A survey of clinical manifestations and risk factors in women with Dupuytren's
      disease.
AB  - Dupuytren's disease is very common, with a prevalence of up to 40% in the
      Scandinavian population. Although many epidemiological surveys have been
      conducted, little is known about its aetiology. Multiple risk factors in
      Dupuytren's disease have been identified. About 80% of the affected patients are
      male. Even though recent data suggest similar outcome after surgical treatment in
      the female patient, recurrence after surgery is more frequent. To assess
      Dupuytren's disease in women, a record analysis and a survey of risk factors was
      conducted in 130 female patients surgically treated at our institution between
      1988 and 2005. With a response rate of 52%, 65 women were included (6 patients
      were confirmed dead). The mean age of onset of the disease was 50 years and 6
      months. After a mean follow-up of 7 years and 7 months (2y1m to 21y9m), recurrent
      disease after surgery was reported in 42%. Bilateral disease was present in 54%,
      unilateral in 26% right and 20% left hands. The fifth finger was involved in 77%,
      the 4th finger in 48% and the 1st ray in 14%. Ectopic lesions were seen in 19%,
      with a positive family history in 55%. Only one patient had a confirmed alcohol
      abuse; 22% were smokers. There were 32% manual workers. Shoulder pain was present
      in 54% of the patients, with confirmed diagnosis of frozen shoulder syndrome in
      45%. High cholesterol was diagnosed in 39% and only 6% had diabetes. Epilepsy was
      seen in 5%. High disease recurrence and factors related to an aggressive course
      of the disease are present in female patients with Dupuytren's contracture, with
      a high family history occurrence, bilateral disease and associated Ledderhose
      disease. Several known risk factors were present: high cholesterol, smoking and
      manual work. Frozen shoulder showed a very high prevalence in women with
      Dupuytren's disease.

PMID- 18811028
TI  - Evaluation of Hylamer-zirconia hip arthroplasty in patients less than 50 years of
      age.
AB  - The purpose of this prospective study was to determine the clinical outcomes of
      patients who had total hip arthroplasties with a zirconia (Zr) - Hylamer pairing.
      Fifty-eight consecutive cemented total hip arthroplasties with a Hylamer cup and
      22.25 mm Zr head were examined for component wear and failure. The SF-36 and Mayo
      hip score were used to evaluate patient outcome. Regression and Kaplan Meier
      survival analyses were used to determine outcome. The mean Mayo postoperative
      score was 94 points. The median post-operative SF-36 score was 84 points. The
      mean rate of wear was 0.097 +/- 0.02 mm/year, with no evidence of loosening or
      significant osteolysis at a minimum follow-up of 5 years. Kaplan-Meier survival
      analysis was 98% at 3-year follow-up and 94% at 5-year follow-up. This study has
      confounded previous reports relating to Zirconia-Hylamer counter-surface
      components.

PMID- 18811029
TI  - Medium-term results of patellofemoral joint arthroplasty.
AB  - The results of a multi-surgeon, multi-implant series of patellofemoral joint
      arthroplasties performed over a ten year period are presented. All patellofemoral
      joint arthroplasties performed from 1997 to 2006 were retrospectively reviewed
      using case notes, radiographs and clinic appointments until their latest follow
      up period. One hundred and one arthroplasties in 91 patients were followed up for
      an average period of 48 months (range 6-96 months). The average age was 57 years
      with female patients thrice as common as male patients. There were 5 (5%)
      complications with 1 deep infection and 4 stiff knees. Thirty five subsequent
      procedures were performed in 28 patients including arthroscopic debridement in
      18, arthroscopic lateral retinacular release in 8, tibial tuberosity transfer in
      3, manipulation for stiffness in 2, and revision to total knee arthroplasty in 4
      patients (3 for progression of tibiofemoral osteoarthritis and 1 for infection).
      The necessity of further surgeries in one third of the study group suggests that
      close follow-up of these patients is needed to address any concerns that can be
      easily resolved.

PMID- 18811030
TI  - Do we need to replace the patella in knee arthroplasty for rheumatoid disease?
AB  - We have examined the anterior knee function in two patient groups who had
      undergone primary knee arthroplasty without patellar resurfacing to identify
      differences for osteoarthrosis compared with rheumatoid disease. We identified
      two consecutive series of patients who had undergone knee replacement surgery for
      either osteoarthritis or rheumatoid disease between 1992 and 1994 under the care
      of a single surgeon using the same implant and surgical technique. There were 90
      patients in each group. All were examined and asked to complete a questionnaire
      so as to determine Hospital for Special Surgery (HSS) score, Western Ontario and
      McMasters Universities Osteoarthritis Index (WOMAC) score, Bartlett patellar
      score and a Visual Analogue score (VAS) for any persistent anterior knee pain at
      rest. We failed to identify any significant differences in terms of anterior knee
      function between these two groups of patients. The re-operation rate was similar
      for both groups. It would appear that primary knee replacement for rheumatoid
      disease is met with a similarly good outcome for anterior knee function despite
      absence of patellar resurfacing. We would question the contention that patellar
      resurfacing is necessary for patients undergoing knee replacement for rheumatoid
      disease.

PMID- 18811031
TI  - Clinical outcome of surgical intervention for recalcitrant infero-medial heel
      pain.
AB  - A retrospective review was conducted in 28 patients (31 feet) with recalcitrant
      infero-medial heel pain, to assess the clinical outcome of a combined release of
      the first branch of the lateral plantar nerve and the plantar fascia. All
      patients were questioned by telephone interview on their pre- versus post
      operative level of pain and function (based on the Kitaoka mid-foot scale and the
      visual analog scale), and their satisfaction with the result of the intervention.
      Limitations of functional activity decreased, maximum walking distance increased
      and the level of pain decreased from 8.9 to 1.4 on the visual analog scale. The
      majority of patients was satisfied with the surgery (90.3%) and would undergo the
      same procedure again or would recommend it (92.9%). While conservative management
      remains the gold standard for treatment of infero-medial heel pain and/or plantar
      fasciitis, patients with recalcitrant disease usually can be effectively treated
      surgically with a combined release of the plantar fascia and the first branch of
      the lateral plantar nerve.

PMID- 18811032
TI  - Correlation between clinical outcome of surgically treated clubfeet and different
      radiological parameters.
AB  - The goal of this study was to determine the relationship between the clinical
      outcome of surgically treated clubfeet and several radiological parameters. The
      talocalcaneal angle, talocalcaneal index, talo-first metatarsal angle and the
      calcaneo-first metatarsal angle were measured on anteroposterior and lateral
      radiographs of 54 children with 70 idiopathic clubfeet treated surgically between
      2000 and 2004. Their age at surgery ranged from 4 to 23 months. These
      radiological parameters were compared with the clinical results. Follow-up was
      conducted after 24 to 69 months following surgery. Using the functional rating
      system of Laaveg and Ponseti, results were graded as excellent in 28.6% (20
      feet), good in 40% (28 feet), fair in 17.1% (12 feet) and poor in 14.3% (10
      feet). There was a statistically significant correlation between the clinical
      results and two angles: the talo-first metatarsal angle on the anteroposterior
      radiograph and the calcaneao-first metatarsal angle on the lateral radiograph.
      These two angles should be considered when designing an evaluation system of
      clubfeet.

PMID- 18811033
TI  - Correction of adolescent hallux valgus by proximal crescentic osteotomy of the
      first metatarsal.
AB  - Thirty nine surgical hallux valgus corrections in 32 adolescents (7 bilateral)
      performed between 1994 and 2001 were retrospectively studied. The mean age at the
      time of surgery was 14.2 years. The operation consisted of a proximal dome
      osteotomy of the first metatarsal, excision of the medial protuberance, lateral
      capsular and adductor release, and distal medial soft tissue plication. The
      patients were followed for an average of 42 months (range 32 to 62). Post
      operative evaluation was based on the duPont bunion rating score. The result was
      excellent in 11 feet, good in 22 cases, fair in 5 and poor in 1 case. Using
      subjective criteria of the duPont score, such as cosmesis and discomfort, a
      satisfactory result was achieved in 35 feet (90%). Our opinion is that correction
      of the angle between the 1st and 2nd metatarsal as well as preservation of the
      length of the first metatarsal are of crucial importance in the surgical
      treatment of adolescent hallux valgus.

PMID- 18811034
TI  - CT-guided percutaneous transpedicular biopsy for the diagnosis of vertebral
      lesions.
AB  - The authors report the results of a prospective study about CT-guided
      percutaneous transpedicular vertebral biopsy in 23 patients, 11 male and 12
      female, with a mean age of 45 years (range, 17-90 years). Eleven biopsies were
      performed at a thoracic level, 12 at a lumbar or sacral (one) level. A diagnosis
      was obtained in 21 out of 23 patients (91.3%); in the remaining two cases an open
      biopsy was necessary, which led to the diagnosis of aneurysmal bone cyst. CT
      guided percutaneous transpedicular biopsy is an effective and safe method. The
      transpedicular approach is especially useful for thoracic lesions, because it
      avoids pulmonary complications such as pneumothorax, without increasing the rate
      of neurologic problems. This method is not suitable for the diagnosis of
      aneurysmal bone cysts.

PMID- 18811035
TI  - Degeneration of non-fused segments after floating lumbar fusion.
AB  - Degeneration of the disc or discs between two fused spinal segments has been
      termed "floating disc disease". The purpose of this retrospective study was to
      show the radiological evolution of the floating disc(s) and the relationship
      between floating disc degeneration and segmental lordosis, lumbar lordosis and
      pelvic incidence. Twenty patients, with a mean age of 49.9 years, with
      symptomatic lumbar degenerative disc disease or low grade spondylolisthesis, who
      failed non-operative treatment and underwent fusion of 2 or more noncontiguous
      spinal segments, were included in this study. The radiographs of the floating
      discs were graded with the modified Gore System. The mean follow-up was 4.2
      years. Forty-seven levels were fused and 27 floating discs were studied (13
      single, 7 double). Five out of 27 floating discs (18%), in 4 patients,
      progressively degenerated. None of the floating discs degenerated more than two
      radiographic grades and none needed additional surgery. Postoperatively, 3 out of
      5 degenerated floating discs had decreased segmental lordosis, while the other
      two had no change; this difference was not significant (p = 0.08). Neither was
      there any significant correlation between floating disc degeneration and lumbar
      lordosis L1-S1 (p > 0.10) or pelvic incidence (p > 0.10). This study shows that
      the effect of floating fusion on floating discs is the same as the effect of a
      contiguous fusion on adjacent discs.

PMID- 18811036
TI  - The flexible Triac-Brace for conservative treatment of idiopathic scoliosis. An
      alternative treatment option?
AB  - The flexible Triac-Brace was developed to improve cosmetic appearance and wearing
      comfort. It was evaluated in this study with respect to primary curve correction
      in idiopathic scoliosis (IS). Twenty patients (15 girls, 5 boys, mean age: 12.5)
      with a diagnosis of IS were treated with the Triac-Brace. Lumbar curves showed an
      initial average Cobb angle of 26 degrees (SD = 9 degrees), thoracic curves of 25
      degrees (SD = 7 degrees). After 6.2 weeks the primary curve correction was
      measured (Cobb). Further radiological follow-up was done every 6 months during
      the average wearing time of 15 months. Cosmesis and wearing comfort were assessed
      by a valid scoring system (Quality of Life Profile for Spine Deformities). We
      observed a primary correction of 41% in lumbar curves (n = 12) (significant, t
      test), and 10% in thoracic curves (n = 17) (not significant, t-test). An increase
      in correction over time as reported by Veldhuizen et al was not seen. Curve
      progression was noted in five patients (average 12 degrees). The scores for
      cosmesis (4.2/5) and flexibility of the back (4.6/5) were high. Ninety percent of
      the patients reported a wearing time of 22-23 h. We do not recommend treatment of
      thoracic or double curves with the Triac-Brace. Larger studies are necessary to
      assess the effectiveness in lumbar curves. The improved wearing comfort is a
      potential advantage.

PMID- 18811037
TI  - Cauda equina syndrome secondary to lumbar disc herniation.
AB  - The authors conducted a retrospective study of 8 cases of cauda equina syndrome
      (CES) due to a herniated lumbar intervertebral disc, in order to highlight the
      clinical presentation and outcome after urgent surgical decompression. Between
      1995 and 1999, 8 patients (4 men and 4 women) with ages ranging from 43 to 64
      years (mean 53 years) presented with CES. There were two modes of presentation:
      acute to subacute (4 patients) and insidious (4 patients). In 3 patients the
      precipitating factor was stooping, with or without heavy lifting. One patient
      gave a history of stooping and heavy lifting, followed by manipulation therapy.
      Urinary bladder involvement was present in all patients (100%). Perianal sensory
      involvement was present in four cases, bilateral in two and unilateral in the
      other two. Seven patients had complete recovery of bladder function. One patient
      had residual urinary symptoms, though she was continent; she had been operated
      upon within 33 hours, within the classical 48 hours suggested by larger series.
      Residual weakness of lower limb muscles was present in three cases. In this small
      series there was no distinct correlation between timing of operation and results.
      Conclusion : The classical presentation of CES is not obvious. Surgery as an
      emergency is recommended: within 48 hours, according to the old rule. Even if
      surgery is done late due to delayed presentation, significant improvement in the
      bladder function can still be expected.

PMID- 18811038
TI  - MRSA colonisation in spinal cord injury: implications on patients rehabilitation.
AB  - MRSA has become a major cause of nosocomial and community acquired infections in
      the past few years. Our hypothesis is that MRSA colonisation affects the length
      of stay in hospital, thereby adding a strain on resources. Data from the last 20
      patients admitted to the Spinal Injury Care Unit (SICU) who were MRSA positive
      (study group) have been analysed and then matched with data from 20 patients who
      were MRSA negative (control group) to compare their total hospital stay and the
      factors which affect the length of hospital stay. The mean age of the study group
      patients was 38.8 years. The average time between injury and admission in SICU
      was 76.5 days in the study group compared to 28.7 days in the control. The mean
      stay duration was 412.15 days in the study group as opposed to 187.2 days in the
      control group. Nearly 45% had developed pressure sores in the study group as
      compared to 25% in the control group. Our study indicates that MRSA colonisation
      in spinal injured patients leads to longer hospital stay, delay in admission to
      spinal care units, and development of pressure sores and further infection. These
      factors have adverse effects on patients' rehabilitation.

PMID- 18811039
TI  - Suction during orthopaedic surgery. How safe is the suction tip?
AB  - The use of a suction system is mandatory in most orthopaedic procedures. In the
      unlikely event of contamination of the system, deep wound infection could occur,
      jeopardising the operation. We have prospectively studied 50 patients who
      underwent elective and orthopaedic trauma procedures during which a suction
      system was used. At the end of each procedure the suction catheter tip was sent
      for culture and microbiology. The suction tips showed bacterial contamination in
      27 cases (54%). Staphylococcus species were responsible in 21 cases (77.8%). The
      tip was contaminated in only 1/11 procedures lasting less than one hour (9.1%),
      as compared with 26/39 procedures when operative time exceeded one hour (66.7%).
      However, deep wound infection was recorded in only one case. We believe that
      despite the low risk of deep wound infection, changing the suction tip every hour
      in long orthopaedic procedures or using the on/off switch is well justified in an
      effort to minimise the chances of deep wound infection.

PMID- 18811040
TI  - The role of bone morphogenetic protein-7 (Osteogenic Protein-1) in the treatment
      of tibial fracture non-unions. An overview of the use in Belgium.
AB  - The evolution of a fracture non-union is complex; treatment strategies are
      therefore challenging. The use of BMP-7 could be an interesting adjunct. We
      present an overview of the monitored use of this product in tibial non-unions in
      Belgium. Our retrospective data covers 53% (62 patients) of the cases in which it
      was used between 2001 and 2006. Questionnaires were sent to surgeons who had been
      using BMP-7 (OP-1) in tibial non-unions in Belgium. Of 55 surgeons contacted, 27
      who had been treating 62 patients with a non-union of a tibial fracture
      responded. These fractures were most commonly treated with an external fixator
      and 50% of them had already received some form of graft material. Non-union was
      diagnosed after a median of 365 days (range, 123-1212). Treatment with OP-1
      resulted in a clinical healing rate of 79.6% and a radiographic healing rate of
      84.9%. Union was reported after a median of 230 (32-872) days clinically and 232
      (32-739) days radiographically. We documented a large number of cases of use of
      BMP-7 in tibial non-union in Belgium. The healing rates of around 80% are
      comparable to other reports on success rates with BMP-7. Many cases presented
      originally with open fractures, infected wounds or fractures with bone loss. This
      makes the reported results even more promising. Further studies are needed to
      analyse the socio-economical value of this relatively expensive treatment.

PMID- 18811041
TI  - Vacuum-assisted wound closure (VAC) with simultaneous bone transport in the leg:
      a technical note.
AB  - Successful treatment of infected non union in long bone fractures has always been
      a challenge. Segmental excision followed by bone transport is one of the common
      modalities of treatment in such difficult cases. The soft tissue coverage of the
      resulting wounds was however not well described in the literature. The authors
      would like to report a simple technique that was used. After segmental bone
      excision and application of a ring fixator, a vacuum assisted closure (VAC)
      dressing was applied to the wound, which resulted in not only a remarkable growth
      of granulation tissue that filled the soft tissue defect, but also satisfactory
      signs of bony union across the docking site. The authors would like to emphasise
      the benefits of a simple method such as VAC therapy in enhancing cover of the
      large soft tissue defects during simultaneous bone transportation, and thus
      avoiding complex plastic surgical procedures.

PMID- 18811042
TI  - Distal humerus lateral condyle fracture and Monteggia lesion in a 3-year old
      child: a case report.
AB  - We describe a case of a Monteggia fracture dislocation and an ipsilateral lateral
      humeral condyle fracture in a 3-year-old child. This is a rare combination of
      injuries with no previously reported cases in the literature. This case
      emphasises that when a fracture is detected around an elbow there should be a
      high index of suspicion for other injuries in the region.

PMID- 18811043
TI  - The natural history of a mistreated ipsilateral Galeazzi and Monteggia lesion:
      report of a case 39 years post-injury.
AB  - Galeazzi injury combined with ipsilateral Monteggia lesion is extremely rare. A
      45-year-old male patient with a mistreated Galeazzi lesion combined with an
      ipsilateral Monteggia fracture at the age of 6 is presented. Thirty-nine years
      post-injury his elbow was asymptomatic and stable and his distal radioulnar and
      radiocarpal joints were also asymptomatic. The strength of the limb was equal to
      the unaffected contralateral upper limb and he was able to work manually as a
      waiter for the last 20 years without any problem. The only obvious defect was a
      30 degrees lack of elbow flexion and a 10 degrees lack of forearm pronation in
      comparison to the normal side.

PMID- 18811044
TI  - Correction of polydactyly in patients with Ellis-van Creveld syndrome: a report
      of two cases.
AB  - Ellis-van Creveld syndrome (EVC) is a rare chondroectodermal dysplasia presenting
      several skeletal manifestations and congenital heart malformations. Polydactyly
      is the most frequent skeletal anomaly. The authors report two cases of EVC
      syndrome with different manifestations, which underwent surgical treatment for
      polydactyly.

PMID- 18811045
TI  - Intraoperative dislocation of the prosthetic femoral head into the pelvis during
      total hip arthroplasty.
AB  - An 86-year-old woman with severe osteoarthritis and severe pain in her left hip
      underwent total hip arthroplasty. Intraoperatively, the 22 mm femoral head
      impinged on the anterior rim of the acetabulum during a reduction maneuver, and
      disengagement of the femoral head from the neck occurred with migration of the
      head over the pelvic brim along the inner table of the pelvis. This complication
      related with hip arthroplasty is underestimated by many orthopaedic surgeons.

PMID- 18811046
TI  - Diaphyseal sclerotic osteosarcoma presenting as a pathological fracture.
AB  - A diaphyseal, intramedullary, highly sclerotic lesion presenting as a
      pathological fracture, without a periosteal reaction or an appreciable soft
      tissue component on radiographs was investigated. A discrepancy between the MRI
      and histopathological findings led to marginal excision of the lesion only to
      reveal later that it was a sclerotic variety of osteosarcoma. Such a presentation
      has not been reported in literature as per our knowledge. We forfeited the
      opportunity of limb salvage by doing initial marginal excision and fixation. In
      such circumstances, a representative biopsy is critical and repeat biopsy is
      warranted before going for definitive management.

PMID- 18811047
TI  - Bizarre parosteal osteochondromatous proliferation (Nora's lesion) of the
      forefoot.
AB  - Nora's tumour is an uncommon benign tumour, involving mostly tubular bones of
      hands and feet, and characterized by a proliferation of chondroid, bony and
      fibrous tissues. Main differential diagnoses are osteochondroma, chondrosarcoma,
      and osteosarcoma. The authors report a case involving the left foot. The
      diagnosis was suspected by imaging characteristic features and was confirmed by
      histological examination. Treatment was surgical, with complete excision. There
      are no clinical or radiological signs of recurrence on further review one year
      postoperatively.

PMID- 18811048
TI  - Multiple-level cement vertebroplasty in patients with vertebral commpression
      fractures from osteodystrophy in chronic liver disease.
AB  - Multiple compression fractures of osteoporotic vertebrae are common in patients
      with a liver transplant or with chronic liver disease. The authors describe two
      such patients, treated with percutaneous cement vertebroplasty at 12 levels,
      respectively in 4 and in 2 sessions. No complications were seen after follow-up
      periods of 12 and 8 months respectively. However, this is not a grant for the
      future, and further followup is necessary. Multiple-level cement vertebroplasty
      should not be generalized before further experience is gained. Moreover, medical
      treatment continues to play an important role.

PMID- 18811049
TI  - Statin-induced muscular symptoms: a report of 3 cases.
AB  - Although the prescription of statin medication has increased worldwide and
      especially in Europe, its musculoskeletal side effects and their management
      strategy has not been highlighted in orthopaedic literature. We present three
      cases of statin-induced musculoskeletal symptoms which presented to an
      orthopaedic department. There were two patients with statin induced muscle pain
      (one in the thigh and one around the hip), and one with both myositis (with
      raised creatine kinase) and lupus-like symptoms. All of the symptoms resolved
      with stopping the statin. Muscle pain (often with normal creatine kinase) is the
      commonest side effect of statins. It is usually bilateral, but two of our cases
      presented with unilateral symptoms which made it more difficult to exclude a
      primary orthopaedic pathology. The widespread use of statins is likely to lead to
      an increase in the number of patients presenting to orthopaedic surgeons with
      muscle pain. It is important to consider muscle pain induced by statins in the
      differential diagnosis of acute or chronic pain in the limbs.

PMID- 18811050
TI  - Oncogenes meet metabolism. From deregulated genes to a broader understanding of
      tumour physiology. Preface.

PMID- 18811051
TI  - Role of the metabolic stress responses of apoptosis and autophagy in tumor
      suppression.
AB  - Metabolic stress is an important stimulus that promotes apoptosis-mediated tumor
      suppression. Metabolic stress arises in tumors from multiple factors that include
      insufficient nutrient supply caused by deficient angiogenesis and high metabolic
      demand of unrestrained cell proliferation. The high metabolic demand of tumor
      cells is only exacerbated by reliance on the inefficient process of glycolysis
      for energy production. Recently it has become clear that tumor cells survive
      metabolic stress through the catabolic process of autophagy. Autophagy also
      functions as a tumor suppression mechanism by preventing cell death and
      inflammation and by protecting the genome from damage and genetic instability.
      How autophagy protects the genome is not yet clear but may be related to its
      roles in sustaining metabolism or in the clearance of damaged proteins and
      organelles and the mitigation of oxidative stress. These findings illuminate the
      important role of metabolism in cancer progression and provide specific
      predictions for metabolic modulation in cancer therapy.

PMID- 18811052
TI  - The interplay between MYC and HIF in the Warburg effect.
AB  - c-MYC and the hypoxia-inducible factors (HIFs) are critical factors for
      tumorigenesis in a large number of human cancers. While the normal function of
      MYC involves the induction of cell proliferation and enhancement of cellular
      metabolism, the function of HIF, particularly HIF-1, involves adaptation to the
      hypoxic microenvironment, including activation of anaerobic glycolysis. When MYC
      dependent tumors grow, the hypoxic tumor microenvironment elevates the levels of
      HIF, such that oncogenic MYC and HIF collaborate to enhance the cancer cell's
      metabolic needs through increased uptake of glucose and its conversion to
      lactate. HIF is also able to attenuate mitochondrial respiration through the
      induction of pyruvate dehydrogenase kinase 1 (PDK1), which in part accounts for
      the Warburg effect that describes the propensity for cancers to avidly take up
      glucose and convert it to lactate with the concurrent decrease in mitochondrial
      respiration. Target genes that are common to both HIF and MYC, such as PDK1,
      LDHA, HK2, and TFRC, are therefore attractive therapeutic targets, because their
      coordinate induction by HIF and MYC widens the therapeutic window between cancer
      and normal tissues.

PMID- 18811053
TI  - Using metabolomics to monitor anticancer drugs.
AB  - The metabolome of a cancer cell is likely to show changes after responding to an
      anticancer drug. These changes could be used to decide whether to continue
      treatment or, in the context of a drug trial, to indicate whether the drug is
      working and perhaps its mechanism of action. (Nuclear) magnetic resonance
      spectroscopy (NMR/MRS) methods can offer important insights into novel anticancer
      agents in order to accelerate the drug development process including time-course
      studies on the effect of a drug on its site of action (termed pharmacodynamics),
      in this case the cancer. In addition, some classes of anticancer agents currently
      under development (e.g. antiangiogenics) are designed to be used in combination
      with other drugs and will not cause tumour shrinkage when used as single agents
      in Phase 1 clinical trials. Thus NMR/MRS may have a special role in monitoring
      the pharmacodynamic actions of such drugs in early-phase clinical trials. This
      review focuses on the use of ex vivo NMR and in vivo MRS methods for monitoring
      the effect of some novel anticancer drugs on the cancer metabolome. Ex vivo NMR
      methods are complementary to in vivo measurements, as they can provide additional
      information and help in the interpretation of the in vivo data.

PMID- 18811054
TI  - Biomarker discovery for drug development and translational medicine using
      metabonomics.
AB  - There exists at present an urgent desire for better biomarkers, especially in the
      context of pharmaceutical drug development and in the detection and management of
      disease. Many researchers in the area of biomarker discovery and development have
      turned to the "-omics" sciences as a way of addressing these needs. Metabolic
      profiling, or metabonomics, defines the metabolic phenotype and offers a source
      of novel biomarkers that have better potential to translate effectively. This
      review will discuss the broad philosophy and motivations behind metabonomics, and
      illustrate the case with applications relevant to pharmaceutical development and
      patient management. Particular focus will be paid to the potential of
      metabonomics to contribute to biomarker discovery in toxicology and cancer
      research.

PMID- 18811055
TI  - Pyruvate kinase type M2: a key regulator within the tumour metabolome and a tool
      for metabolic profiling of tumours.
AB  - Normal proliferating cells and tumour cells in particular express the pyruvate
      kinase isoenzyme type M2 (M2-PK, PKM2). The quaternary structure of M2-PK
      determines whether the glucose carbons are degraded to pyruvate and lactate with
      production of energy (tetrameric form) or channelled into synthetic processes,
      debranching from glycolytic intermediates such as nucleic acid, amino acid and
      phospholipid synthesis. The tetramer:dimer ratio of M2-PK is regulated by
      metabolic intermediates, such as fructose 1,6-P2 and direct interaction with
      different oncoproteins, such as pp60v-src kinase, HPV-16 E7 and A-Raf. The
      metabolic function of the interaction between M2-PK and the HERC1 oncoprotein
      remains unknown. Thus, M2-PK is a meeting point for different oncogenes and
      metabolism. In tumour cells, the dimeric form of M2-PK is predominant and has
      therefore been termed Tumour M2-PK. Tumour M2-PK is released from tumours into
      the blood and from gastrointestinal tumours also into the stool of tumour
      patients. The quantification of Tumour M2-PK in EDTA plasma and stool is a tool
      for early detection of tumours and therapy control.

PMID- 18811056
TI  - Molecular imaging of tumor metabolism and apoptosis.
AB  - Increased metabolism has been found to be one of the most prominent features of
      malignant tumors. This property led to the development of tracers for the
      assessment of glucose metabolism and amino acid transport and their application
      for tumor diagnosis and staging. Prominent examples are fluorodeoxyglucose,
      methionine and tyrosine analogs, which have found broad clinical application.
      Since quantitative procedures are available, these techniques can also be used
      for therapy monitoring. Another approach may be based on the noninvasive
      detection of apoptosis with tracers for phosphatidyl-serine presentation and/or
      caspase activation as surrogate markers for therapeutic efficacy. Finally, the
      evaluation of hypoxia with nitroimidazoles may be a valuable tool for prognosis
      and therapy planning.

PMID- 18811057
TI  - Minimally invasive biomarkers for therapy monitoring.
AB  - Development of new drugs and optimal application of the drugs currently in use in
      clinical chemotherapy requires the application of biomarkers. Ideally, these
      biomarkers would stratify patients so that only those patients likely to respond
      to a particular therapy receive that therapy. However, that is not always
      feasible, and an alternative is to make use of early response biomarkers to
      determine the responding population. In this paper, a number of generic (i.e. not
      necessarily specific to the action mechanism of the compound) early-response
      biomarkers are discussed and compared in different models and with three
      compounds with quite different mechanisms of action: a VEGF-R inhibitor (PTK787),
      an mTOR inhibitor (RAD001) and a microtubule stabiliser (EPO906). The methods
      include noninvasive DCE-MRI and PET imaging for measuring tumour vascularity,
      metabolism and proliferation, as well as the minimally invasive WIN method for
      measuring tumour interstitial pressure (IFP). The data show that drug-induced
      changes in IFP (delta IFP) involve mechanism-dependent changes in the tumour
      vascular architecture, and that delta IFP may be considered a universal generic
      early-response marker of tumour response to therapy.

PMID- 18811058
TI  - Use of metabolic pathway flux information in anticancer drug design.
AB  - The metabolic phenotype of tumor cells promote the proliferative state, which
      indicates that (a) cell transformation is associated with the activation of
      specific metabolic substrate channels toward nucleic acid synthesis and (b)
      increased expression phosphorylation, allosteric or transcriptional regulation of
      intermediary metabolic enzymes and their substrate availability together mediate
      unlimited growth. It is evident that cell transformation due to various K-ras
      point mutations is associated with the activation of specific metabolic substrate
      channels that increase glucose channeling toward nucleic acid synthesis.
      Therefore, phosphorylation, allosteric and transcriptional regulation of
      intermediary metabolic enzymes and their substrate availability together mediate
      cell transformation and growth. In this review, we summarize opposite changes in
      metabolic phenotypes induced by various cell-transforming agents, and tumor
      growth-inhibiting drugs or phytochemicals, or novel synthetic antileukemic drugs
      such as imatinib mesylate (Gleevec). Metabolic enzymes that further incite growth
      signaling pathways and thus promote malignant cell transformation serve as high
      efficacy nongenetic novel targets for cancer therapies.

PMID- 18811059
TI  - Cancer diagnostics using 1H-NMR-based metabonomics.
AB  - For several solid human malignancies, currently available serum biomarkers are
      insufficiently reliable to distinguish patients from healthy individuals.
      Metabonomics, the study of metabolic processes in biologic systems, is based on
      the use of 1H-NMR spectroscopy and multivariate statistics for biochemical data
      generation and interpretation and may provide a characteristic fingerprint in
      disease. Here we review our initial experiences utilizing the metabonomic
      approach for discriminating sera from women with epithelial ovarian cancer (EOC)
      from healthy controls. 1H-NMR spectroscopic analysis was performed on
      preoperative serum specimens of 38 EOC patients, 12 patients with benign ovarian
      cysts and 53 healthy women. PCA analysis allowed correct separation of all serum
      specimens from 38 patients with EOC (100%) from all of the 21 premenopausal
      normal samples (100%) and from all the sera from patients with benign ovarian
      disease (100%). In addition, it was possible to correctly separate 37 of 38
      (97.4%) cancer specimens from 31 of 32 (97%) postmenopausal control sera. ROC
      analysis indicated that the sera from patients with and without disease could be
      identified with 100% sensitivity and specificity at the 1H-NMR regions 2.77 parts
      per million (ppm) and 2.04 ppm from the origin (AUC of ROC curve = 1.0). These
      findings indicate that the 1H-NMR metabonomic approach deserves further
      evaluation as a potential novel strategy for the early detection of EOC.

PMID- 18811060
TI  - Human metabolic phenotyping and metabolome wide association studies.
AB  - Metabolic phenotyping in large-scale population studies can yield crucial
      information regarding the impact and interaction of genetic and environmental
      factors with regard to the prevalence and risk of chronic diseases. Spectroscopic
      technologies such as nuclear magnetic resonance (NMR) spectroscopy and mass
      spectrometry (MS) can be used to generate multi-parameter profiles of biological
      samples and together with automated sample delivery and mathematical modelling
      systems, can be used as a high throughput screening tool. The adaptation of these
      metabolic profiling tools from pre-clinical studies in animal models to
      population studies in man is explored and an overview of the current and future
      roles of metabolic phenotyping is described, including the idea of "Metabolome
      Wide Association Screening" focussing on key disease areas such as cardiovascular
      disease and metabolic syndrome, cancers and neurodegeneration.

PMID- 18811061
TI  - Defining personal nutrition and metabolic health through metabonomics.
AB  - A major charter for modern nutrition is to provide a molecular basis for health
      outcome resulting from different food choices and how this could be designed to
      maintain individual health free of disease. Nutrigenomic techniques have been
      developed to generate information at various levels of biological organization,
      i.e. genes, proteins, and metabolites. Within this frame, metabonomics targets
      the molecular characterization of a living system through metabolic profiling.
      The metabolic profiles are explored with sophisticated data mining techniques
      mainly based on multivariate statistics, which can recover key metabolic
      information to be further linked to biochemical processes and physiological
      events. The power of metabonomics relies on its unique ability to assess
      functional changes in the metabolism of complex organisms stemming from multiple
      influences such as lifestyle and environmental factors. In particular, metabolic
      profiles encapsulate information on the metabolic activity of symbiotic partners,
      i.e. gut microflora, in complex organisms, which represent major determinant in
      nutrition and health. Therefore, applications of metabonomics to nutrition
      sciences led to the nutrimetabonomics approach for the classification of dietary
      responses in populations and the possibility of optimized or personalized
      nutritional management.

PMID- 18811062
TI  - Sources of health insurance and characteristics of the uninsured: analysis of the
      March 2008 current population survey.

PMID- 18811063
TI  - Just a new EMT.

PMID- 18811064
TI  - Patience; it's more than a virtue.

PMID- 18811065
TI  - Under parental control.

PMID- 18811066
TI  - Nothing to sneeze at.

PMID- 18811067
TI  - EMS intelligence sensors. Interview by Raphael M Barishansky.

PMID- 18811068
TI  - Let's share best practices.

PMID- 18811069
TI  - Preparing for supervision.

PMID- 18811071
TI  - Cardiac arrest management: Part 2.

PMID- 18811070
TI  - Diversionary tactics.

PMID- 18811072
TI  - Bariatric transport challenges: Part 1.

PMID- 18811073
TI  - Pediatric toxicology: Part 1.

PMID- 18811074
TI  - Beyond the basics: the art of critical thinking. Part 1.

PMID- 18811075
TI  - The road ahead...

PMID- 18811076
TI  - Smile aesthetics.
AB  - The aim of this article is to outline some of the factors practitioners should
      take into consideration when planning optimal smile aesthetics. The components of
      the smile that will be discussed include the smile are, incisor/gingival display,
      smile width, gingival aesthetics, tooth proportionality/symmetry,
      contacts/connectors/embrasures and the dental midlines.

PMID- 18811077
TI  - The effect of retinoic acid on mouse mandibular molar development in vitro, using
      alkaline phosphatase as a molecular indicator of differentiation.
AB  - INTRODUCTION: An excellent model system that links evolutionary biology and
      developmental biology in seeking to understand evolutionary diversity is the
      study of tooth development in mammals. These studies reflect the diversity of
      mammalian radiations which bear on the interpretation of South African fossil
      hominids. Tooth development occurs via epithelio-mesenchymal interactions and
      involves the production of many substances, including alkaline phosphatase, which
      is necessary for dentine and enamel formation. Retinoic acid is a known morphogen
      and is important in tooth development. In excess, retinoic acid has been found to
      alter the formation of teeth. OBJECTIVES: In order to determine whether retinoic
      acid has any effect on tooth morphology, exogenous retinoic acid was administered
      to developing mouse molar teeth in vitro, and alkaline phosphatase was utilized
      as an indicator of differentiation. METHODS: Molars were microdissected from 15.5
      day mouse embryo mandibles and cultured at the air: medium interface with or
      without retinoic acid for seven days. Following fixation and embedding, the
      explants were sectioned for morphological analysis. Alkaline phosphatase activity
      was detected using a modified Gomori's histochemical method. RESULTS AND
      CONCLUSION: Retinoic acid appeared to retard the growth and differentiation of
      the molar explants. This was coincident with reduced alkaline phosphatase.

PMID- 18811078
TI  - Effect of four different opalescence tooth-whitening products on enamel
      microhardness.
AB  - OBJECTIVES: The purpose was to evaluate the effect of various Opalescence tooth
      whitening products on enamel. METHODS AND MATERIALS: Enamel blocks were exposed
      to Opalescence PF 10% Carbamide Peroxide (n = 10), Opalescence PF 20% Carbamide
      Peroxide (n = 10), Opalescence Treswhite Supreme 10% Hydrogen Peroxide (n = 10)
      and Opalescence Quick PF 45% Carbamide Peroxide (n = 10) according to the
      manufacturer's instructions. The control group was enamel blocks (n = 10) kept in
      artificial saliva. The values were obtained before exposure and after the 14-days
      treatment period. Enamel blocks were kept in saliva between treatments. Indent
      marks on enamel blocks were examined using the scanning electron microscope for
      treatment effects. RESULTS: All four different Opalescence products damaged
      enamel. The most damage was done when treated for a long period (112 hours). SEM
      images also showed damage to enamel by all 4 products. Opalescence with 10% and
      with 20% Carbamide Peroxide showed the highest damage, which also differed
      significantly (p < 0.05) from the saliva control group (p < 0.05; Tukey-Kramer
      Multiple comparison test). CONCLUSION: All 4 Opalescence products damaged enamel.
      Higher damage was done by the 10% carbamide peroxide and 20% carbamide peroxide
      products because of the much longer exposure period (112 hours in comparison to 7
      hours).

PMID- 18811079
TI  - Oral and perioral piercings in Tshwane.
AB  - Oral and perioral piercings have recently become very popular and many patients
      present at dental clinics and practices with jewellery inserted into the oral and
      perioral tissues. It is imperative that oral health care professionals become
      familiar with this practice, become aware of its sequelae, and are able to
      provide oral health education regarding oral hygiene and care of the piercing.
      The present study investigated the sites of oral piercings, complications
      associated with piercings, plaque control procedures practised by piercees, and
      the attitude and behaviour of piercers towards infection control and prevention
      of complications after a piercing. A convenience sample was used and 126 piercees
      and 10 piercers completed a self-administered questionnaire. Of the 126
      participants (107 females and 19 males), 88.10% had a tongue piercing, 19.84% had
      a lip piercing and 7.94% had both. The most common immediate post-procedure
      sequelae were pain (69.05%), swelling (52.38%) and difficulty eating, speaking
      and swallowing (70.63%). Long-term complications were reported by 17.56% of the
      sample, and included chipping of teeth, gingival recession, lesions on the tongue
      and palate, painful gums, and sensitivity of teeth. Oral health professionals
      need to be aware of the risk of damage to soft and hard tissue, and their role in
      informing patients about the potential risks, if consulted before a piercing.

PMID- 18811080
TI  - Idiopathic gingival fibromatosis: a review of the literature and a case report.
AB  - Gingival fibromatosis is characterized by localized or generalized fibrous
      enlargement of the gingivae, mainly around permanent teeth. Gingival fibromatosis
      affects only the masticatory mucosa and does not extend beyond the muco-gingival
      junction. This article describes an unusual case of idiopathic gingival
      fibromatosis with delayed eruption of permanent teeth in an 8 year-old boy. The
      pathogenic mechanisms that bring about gingival fibromatosis are discussed.

PMID- 18811081
TI  - Osteopetrosis: literature review and report of three cases.

PMID- 18811082
TI  - Oral medicine case book 8. Iron deficiency anemia and C. albicans infection of
      the palate and denture surface.

PMID- 18811083
TI  - General practitioner's radiology case 64. Apical cyst.

PMID- 18811084
TI  - Sedation corner 26. Homeopathy.

PMID- 18811085
TI  - The treatment of peri-mucositis and peri-implantitis 2.

PMID- 18811086
TI  - One-stage placement of a 6.0 x 5.7 mm short implant and its restoration with an
      Integrated Abutment Crown.

PMID- 18811087
TI  - Patient history and malpractice defense.

PMID- 18811088
TI  - A view from the other side.

PMID- 18811090
TI  - ICD-9 codes: time for the annual update.

PMID- 18811089
TI  - Dr. Ness' E/M rule.

PMID- 18811091
TI  - The key to implementing change in your practice.

PMID- 18811092
TI  - Launching a community-wide flu vaccination plan.

PMID- 18811093
TI  - Vaccination management: is your practice on target?

PMID- 18811094
TI  - 10 big ideas that could make your practice better.

PMID- 18811095
TI  - Is 'busy' good?

PMID- 18811096
TI  - Conservative aesthetic techniques for discoloured teeth: 1. The use of bleaching.
AB  - There is an increasing move towards more minimally invasive techniques in
      restorative dentistry. This series of two articles discusses conservative
      techniques for the treatment of discoloured teeth. A step-wise approach to
      treatment is promoted to encourage the most conservative solution to achieve
      satisfactory aesthetics. The first of these two articles will describe the use of
      bleaching, whilst part two will go on to describe microabrasion and the use of
      direct composite resin.

PMID- 18811097
TI  - A comparison of two liner materials for use in the ferric sulfate pulpotomy.
AB  - OBJECTIVES: The aim of this study is to compare the success rate obtained when
      applying either a calcium hydroxide (Dycal) base or a zinc oxide-eugenol
      (Kalzinol) base following the traditional ferric sulfate pulpotomy. METHODS:
      Patients were either treated in the chair or under general anaesthesia. All teeth
      had to have radiographic evidence of caries close to the pulp. After haemostasis
      was achieved with damp cotton pellets, ferric sulfate was applied to the pulpal
      stumps. Half of the cases then received a Dycal base followed by a cured layer of
      Vitrebond and a permanent amalgam restoration. The other half of the cases
      received a base of zinc oxide-eugenol (Kalzinol) followed by an amalgam
      restoration. The cases were followed up every 6 months for one year (ie. 2 follow
      up visits). Radiographs were taken at each follow-up visit. RESULTS: Overall,
      teeth treated with Dycal demonstrated a higher failure rate when compared with
      those that received the Kalzinol base. Abscess formation and internal resorption
      were the most common causes of failure. Even though the Kalzinol base
      demonstrated greater success, there were still quite a few failures. CONCLUSION:
      This study demonstrates that calcium hydroxide cannot be recommended as a
      medicament in primary tooth pulpotomies.

PMID- 18811098
TI  - Empirical support for a fissure sealant placement timeframe protocol for black
      South Africans.
AB  - OBJECTIVES: It is recommended that fissure sealants should be placed within four
      years after eruption. Due to considerable variations in the eruption times of
      molar teeth, this recommendation is of limited value from a public health
      perspective. This study, therefore, sought to provide empirical support for a
      public health fissure sealant placement timeframe protocol. METHODS: The first
      and second molar eruption patterns of black South African children aged five to
      seven and 11 to 16 years were analysed in relation to caries experience using the
      1999/2002 National Children's Oral Health Survey. RESULTS: By seven years of age,
      90% of first molars had erupted with a caries experience of 3%. By 14 years of
      age the erupted first molars caries experience was 20%. The 13- and 14-year-olds
      presented with 86% and 98% erupted second molars with a caries experience of 11%
      and 20%, respectively. CONCLUSIONS: The study findings suggest that during school
      based fissure sealant programmes involving black South African children, first
      molars should be targeted at age seven (Grade 1), or as soon as possible
      thereafter. However, caries protection may still be achieved until thirteen years
      of age (Grade 7). Furthermore, second molars should be sealed between the age of
      11 and 13 years (grades 5-7).

PMID- 18811099
TI  - Congenital epulis. A case report.
AB  - Congenital epulis (CE) is an uncommon granular cell lesion of unknown
      pathogenesis and uncertain histogenesis that presents at birth. It is a benign
      hamartoma that may interfere with feeding and respiration. The treatment of CE is
      by simple excision. In the 136 years since CE was first described, more than 200
      cases of CE have been reported in the literature.

PMID- 18811100
TI  - Sedation corner 27. Remedies for anxiety.

PMID- 18811101
TI  - Oral medicine case book 9.

PMID- 18811102
TI  - General practitioner's radiology case 65.

PMID- 18811103
TI  - The treatment of peri-implantitis 3.

PMID- 18811104
TI  - APIC/CHICA-Canada/CBIC infection prevention, control and epidemiology:
      professional and practice standards.

PMID- 18811105
TI  - International Infection Control Council. Global consensus conference on infection
      prevention and control practice for Clostridium difficile associated disease
      (CDAD).

PMID- 18811106
TI  - Hand hygiene.

PMID- 18811107
TI  - More on peripheral PresbyLASIK as a center-distance technique.

PMID- 18811108
TI  - Transmission electron microscopy study of corneal epithelial flaps following
      removal using mechanical scraping, alcohol, and epikeratome techniques.
AB  - PURPOSE: To evaluate various methods of surface ablation by comparing the
      integrity of basal epithelial cells and the basement membrane using transmission
      electron microscopy. METHODS: Corneal epithelial flaps were created using four
      approaches: mechanical removal (using a blunt spatula after application of 0.5%
      proparacaine, mechanical group); conventional LASEK (after application of 20%
      alcohol for 20 seconds, LASEK group); epi-LASIK using PMMA separator (PMMA
      separator group); or epi-LASIK using metal separator (metal separator group).
      Each group comprised epithelial sheets taken from five eyes of five patients. The
      sheets were immediately fixed in glutaraldehyde following removal. The flaps were
      examined using both light and transmission electron microscopy by three
      independent observers blinded to the creation methods, who assessed the adherence
      and integrity of the basement membrane to the basal epithelial layer. RESULTS: In
      the mechanical and PMMA separator groups, > 70% of flap areas had an intact
      basement membrane and normal basal cell integrity. Such integrity was present in
      < 30% of the flap areas in the LASEK group, and in 30% to 70% of the flap areas
      in the metal separator group. Different epikeratomes caused different amounts of
      damage. CONCLUSIONS: Mechanical scraping and epi-LASIK were superior to LASEK in
      terms of preservation of the epithelial basement membrane and basal epithelial
      cells. Preservation ratio may differ depending on the type of epikeratome used.

PMID- 18811109
TI  - Photorefractive keratectomy and butterfly laser epithelial keratomileusis: a
      prospective, contralateral study.
AB  - PURPOSE: To evaluate results of two surface excimer laser refractive surgery
      techniques--photorefractive keratectomy (PRK) and butterfly laser epithelial
      keratomileusis (butterfly LASEK). METHODS: A prospective, randomized, double
      masked study of 51 patients (102 eyes) who underwent laser refractive surgery.
      One eye of each patient was randomized to be operated with PRK and the fellow eye
      with butterfly LASEK. Patients were followed for 1 year. RESULTS: No significant
      difference between groups for distance uncorrected visual acuity (UCVA) (P =
      .559) was noted. At 1 year, 98% (50 eyes) in the PRK group and 96.1% (49 eyes) in
      the butterfly LASEK group reached UCVA of 20/20. Predictability, efficacy,
      safety, and stability were not statistically significant between groups. Safety
      index was 1.0 for PRK and 0.996 for butterfly LASEK. One eye in the butterfly
      LASEK group lost one line of best-spectacle corrected visual acuity. At 12
      months, 94.1% (48 eyes) and 86.3% (44 eyes) in the PRK and butterfly LASEK groups
      (P = .188), respectively, had a spherical equivalent refraction of +/- 0.50
      diopters. Slight haze was observed in both groups. A statistical difference in
      haze between the groups was observed only in the first postoperative month, with
      higher intensity in the butterfly LASEK group (0.18 +/- 0.39) compared to the PRK
      group (0.08+/- 0.21) (P = .04). CONCLUSIONS: Butterfly LASEK had similar
      predictability, efficacy, safety, stability, and haze incidence to PRK for the
      treatment of low to moderate myopia. However, on the second postoperative day,
      PRK showed better UCVA than butterfly LASEK.

PMID- 18811110
TI  - Association between ocular dominance and refraction.
AB  - PURPOSE: To investigate the association between ocular dominance and refraction.
      METHODS: A retrospective study of the cycloplegic refraction of 2453 consecutive
      patients with a mean age of 46 +/- 12 years (range: 18 to 79 years) was
      performed. One thousand one hundred fifty-seven (47%) patients were men and 1296
      (53%) were women. Patients who had previous eye surgery, ocular disease, or > 2
      lines of best spectacle-corrected visual acuity (BSCVA) difference between eyes
      were excluded. Motor ocular dominance was determined using the hole-in-the-card
      test. RESULTS: The right and left eyes were dominant in 67% (1650) and 33% (803)
      of patients, respectively. Males had a higher right eye dominance (70%) than
      females (65%) (P = .0168) with a mean cycloplegic spherical equivalent refracton
      (SE) of -2.12 diopters (D) and -2.38 D, respectively. This higher rate of right
      eye dominance in males was seen at all levels of SE refractive error. Mean BSCVA
      was 20/19 in both right and left eyes (P>.05) with a mean SE of -2.25 +/- 3.63 D
      and -2.26 +/- 3.66 D in the right and left eyes, respectively. Neither mean SE
      difference nor BSCVA difference between eyes was found to correlate with motor
      eye dominance. CONCLUSIONS: Gender appears to be a factor when testing ocular
      dominance but not SE refractive error. The hole-in-the-card dominance test is a
      method that is easy to perform for both patients and clinicians.

PMID- 18811111
TI  - Effect of age on outcomes in patients with keratoconus treated by Intacs using a
      femtosecond laser.
AB  - PURPOSE: To compare the response to Intacs treatment in different age groups of
      patients with keratoconus. METHODS: One hundred nine eyes with keratoconus
      treated with Intacs by using femtosecond laser were divided into three groups
      according to age: group 1, 13 to 19 years old (n = 20); group 2, 20 to 35 years
      old (n = 75), and group 3, 35 to 56 years old (n = 14). All patients had clear
      central corneas and were contact lens intolerant. Pre- and postoperative
      examination data including uncorrected visual acuity (UCVA), best spectacle
      corrected visual acuity (BSCVA), mean refraction spherical equivalent (MRSE), and
      K-readings were evaluated. Pre- and postoperative corneal topographies were
      examined. Visual acuities were detected by Snellen chart. Postoperative follow-up
      was 1 year. RESULTS: The improvement in UCVA, BSCVA, MRSE, and K-readings
      postoperatively in each group was statistically significant. The pre- and
      postoperative differences in UCVA (P = .930), BSCVA (P = .470), MRSE (P = .205),
      and K-readings (P = .545) were similar among groups. CONCLUSIONS: Intacs
      treatment is safe and effective in all age groups. Therefore, it may be an
      alternative treatment to penetrating keratoplasty in adolescent patients with
      keratoconus who are intolerant of contact lenses.

PMID- 18811112
TI  - Influence of age on ocular wavefront aberration changes with accommodation.
AB  - PURPOSE: To perform a quantitative analysis of high order wavefront aberrations
      of the entire optical system of the eye that accompanies accommodation demands in
      the healthy and emmetropic eye. METHODS: Fifty-six healthy emmetropic eyes of 30
      patients were separated into three groups according to age: group 1, 20 to 29
      years; group 2, 30 to 39 years; and group 3, 40 to 49 years. Using iTrace ray
      tracing technology, pupil diameter, objective refraction, and wavefront
      aberrations at accommodation demands of 0 to 4.00 diopters (D) in five 1.00-D
      increments were determined. In analyzing higher order aberrations in the central
      4-mm diameter zone of the pupil, Zernike polynomials were used to study the
      changes associated with accommodation in the magnitude of total higher order
      aberrations, third order aberrations (coma-like aberrations), fourth order
      aberrations (spherical-like aberrations), and the spherical aberration component
      (C4(0)) of the fourth order aberrations. RESULTS: Pupil diameter decreased
      significantly (P < .05) with accommodation demand in each group. Total higher
      order aberrations in group 1 increased significantly (P < .05). No significant
      change was seen in third order aberrations in any group, but fourth order
      aberrations increased significantly (P < .05) in group 1. Spherical aberration
      (C4(0)) showed phase shifts from positive to negative in all groups, but the
      shift in group 3 was minimal, remaining positive even for a 4.00-D accommodation
      demand. CONCLUSIONS: Among higher order aberrations accompanying accommodation
      demands, spherical aberration (C4(0)) in particular showed characteristic
      changes; however, these changes showed age-related disparities. The changes were
      probably due to the effects of reduction in accommodation resulting from age
      related changes in the crystalline lens.

PMID- 18811113
TI  - Optical aberrations in pseudophakic eyes after 2.5-mm Nd:YAG laser capsulotomy
      for posterior capsule opacification.
AB  - PURPOSE: To evaluate aberrometric outcomes in eyes with posterior capsule
      opacification after 2.5-mm Nd: YAG laser capsulotomy compared to pseudophakic
      eyes without posterior capsule opacification. METHODS: Photographic image
      analysis of posterior capsule opacification was performed on 36 eyes that showed
      advanced posterior capsule opacification (case group) and on 36 eyes which showed
      absence of posterior capsule opacification (control group). Best spectacle
      corrected visual acuity (BSCVA) and wavefront analysis were performed in the
      control group and in the case group after 2.5-mm capsulotomy. RESULTS: Mean BSCVA
      in the case group after treatment was significantly higher than before treatment
      (P < .05) and similar to the BSCVA in the control group (P > .1). Aberrometric
      analysis was performed on the control group, but light scattering prevented the
      analysis in posterior capsule opacification before capsulotomy, which was then
      performed after the intervention in 18 (50%) eyes. Mean total high order
      aberrations and 3rd order aberrations were significantly higher in the case group
      than in the control group (P < .05). Fourth and 5th order aberration values were
      similar between the case and control groups (P > .06). CONCLUSIONS: Our wavefront
      results can detect a deterioration of visual quality in patients that underwent a
      2.5-mm Nd:YAG capsulotomy compared to pseudophakic patients not affected by
      posterior capsule opacification. This difference cannot be detected by standard
      visual acuity examination. Further study is needed to clarify whether our high
      order aberration findings were related to small, 2.5-mm capsulotomies and whether
      aberrometry may be indicative for mild to moderate posterior capsule
      opacification.

PMID- 18811114
TI  - Lack of progression of ectasia seven years after LASIK in a highly myopic
      keratoconic eye.
AB  - PURPOSE: To report a patient with clinically evident keratoconus with a
      preoperative spherical equivalent refraction of more than -10.00 diopters (D) who
      underwent successful LASIK with no evidence of progression of ectasia 7 years
      after surgery. METHODS: Interventional case report. RESULTS: A patient with
      clinically evident keratoconus in his left eye underwent bilateral LASIK.
      Preoperative best spectacle-corrected visual acuity (BSCVA) in the left eye was
      20/25 with a manifest refraction of -8.50 -3.25 x 126. Seven years later he
      presented complaining of progressive loss of visual acuity in his left eye. A
      significant posterior subcapsular and nuclear cataract was present in the left
      eye. There was no evidence of ectasia on topography. Cataract surgery was
      performed and BSCVA retumed to 20/20. CONCLUSIONS: LASIK can be successful in
      some eyes with keratoconus, even when deep ablations are performed. It is not
      appropriate to conclude from this case that LASIK is safe in eyes with
      keratoconus. This case raises an important question: why do some eyes with normal
      preoperative topography develop ectasia after LASIK, whereas other eyes with
      significant keratoconus preoperatively remain stableert ke after LASIK?

PMID- 18811115
TI  - Photorefractive keratectomy retreatment after LASIK.
AB  - PURPOSE: To study the results of late photorefractive keratectomy (PRK) in
      corneas originally subjected to LASIK. METHODS: Seven eyes of seven patients who
      had LASIK for myopia were retreated with PRK at least 2 years after LASIK.
      Uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA),
      refraction, and haze were evaluated before and after LASIK and after retreatment
      by PRK. RESULTS: Photorefractive keratectomy retreatment improved BSCVA in six
      (86%) of seven eyes, and one (14%) eye showed no changes. None of the eyes lost
      lines of BSCVA. Five of seven eyes developed mild haze, which disappeared before
      the last postoperative follow-up. CONCLUSIONS: Photorefractive keratectomy
      retreatment performed at least 2 years after LASIK can improve visual acuity. We
      hypothesize that LASIK-induced corneal nerve damage disturbs corneal wound
      healing by increasing the tendency for development of haze.

PMID- 18811116
TI  - Introduction to the proceedings of the Third International Congress of Corneal
      Cross-Linking.

PMID- 18811117
TI  - Immunofluorescence confocal microscopy of porcine corneas following collagen
      cross-linking treatment with riboflavin and ultraviolet A.
AB  - PURPOSE: To assess ultrastructural stromal modifications in porcine corneas after
      riboflavin and ultraviolet A (UVA) exposure using immunofluorescence confocal
      imaging. METHODS: Twenty-five freshly enucleated porcine eyes were enrolled in
      the study. Five eyes served as control (group I). Twenty eyes had their
      epithelium removed (groups I, II, IV, and V) and five eyes had their epithelium
      intact (group III). Groups II and III were cross-linked with riboflavin 0.1%
      solution (10 mg riboflavin-5-phosphate in 10 mL 20% dextran-T-500) and exposed to
      UVA (365 nm, 3 mW/cm2) for 30 minutes. Group IV included five eyes soaked with
      riboflavin without posterior irradiation, and group V included five eyes
      irradiated, without previous exposure to riboflavin. Ultra-thin sections (8
      microm) of the corneas were stained with anti-collagen I and DAPI and their
      fluorescence was revealed under confocal microscopy. RESULTS: Only the cross
      linked corneas (group II) showed a pronounced, highly organized anterior
      fluorescence zone of 182.5 +/- 22.5 microm. Using DAPI staining, an anterior and
      concentrated displacement of cell nuclei due to collagen compaction was observed
      after crosslinking (group II). No structural changes were observed in all other
      groups. CONCLUSIONS: The cross-linking treatment effect can be directly
      visualized using confocal fluorescence imaging, allowing for a quantitative
      analysis. Cross-linked corneas showed a pronounced and limited anterior zone of
      organized collagen fibers, which was not observed in the other groups. Treatment
      of the cornea with riboflavin and UVA without previous deepithelialization did
      not induce any cross-linking effect. Consequently, to facilitate diffusion of
      riboflavin throughout the corneal stroma, the epithelium should be removed as an
      important initial step in the treatment.

PMID- 18811118
TI  - A randomized controlled trial of corneal collagen cross-linking in progressive
      keratoconus: preliminary results.
AB  - PURPOSE: This prospective, randomized, controlled trial aims to provide evidence
      in relation to the efficacy and safety of corneal collagen cross-linking (CXL) in
      the management of progressive keratoconus. METHODS: Eligible eyes were separately
      randomized into either treatment or control groups. Collagen crosslinking was
      performed using 0.1% riboflavin (in 20% dextran T500) and ultraviolet A (UVA)
      irradiation (370 nm, 3 mW/cm2, 30 min) in accordance with a previously published
      protocol. At each review, a full clinical ophthalmic examination was performed
      including endothelial cell count and confocal microscopy. RESULTS: To date, 66
      eyes of 49 patients with documented progression of keratoconus have been enrolled
      and randomized. Interim analysis of treated eyes showed a flattening of the
      steepest simulated keratometry value (K-max) by an average of 0.74 diopters (D)
      (P = .004) at 3 months, 0.92 D (P = .002) at 6 months, and 1.45 D (P = .002) at
      12 months. A trend toward improvement in best spectacle-corrected visual acuity
      was also observed. In the control eyes, mean K-max steepened by 0.60 D (P = .041)
      after 3 months, by 0.60 D (P = .013) after 6 months, and by 1.28 D (P < or =
      .0001) after 12 months. Best spectacle-corrected visual acuity decreased by
      logMAR 0.003 (P = .883) over 3 months, 0.056 (P = .092) over 6 months, and 0.12
      (P = .036) over 12 months. No statistically significant changes were found for
      spherical equivalent or endothelial cell density. CONCLUSIONS: Preliminary
      results of this randomized controlled trial suggest a temporary stabilization of
      all treated eyes after CXL.

PMID- 18811119
TI  - Intacs implantation with sequential collagen cross-linking treatment in
      postoperative LASIK ectasia.
AB  - PURPOSE: To report the postoperative course and refractive results of each eye of
      a patient with postoperative LASIK ectasia for whom Intacs SK (severe
      keratoconus, Addition Technology Inc) implantation and collagen crosslinking
      (CXL) treatments were performed. METHODS: A 27-year-old man with postoperative
      LASIK ectasia with best spectacle-corrected visual acuity (BSCVA) of 20/60 and
      20/80 in the right and left eyes, respectively, was operated for Intacs SK
      implantation for both eyes. Spherical equivalent refraction and mean keratometric
      values in the right and left eyes were -14.50 diopters (D) and -10.50 D and 56.20
      D and 50.70 D, respectively. Following bilateral Intacs SK implantation, CXL was
      performed after 1 day in the left eye and 1 month in the right eye. RESULTS:
      During follow up, there was an improvement in visual acuity and decrease in
      manifest refraction and keratometric values in both eyes. A slight regression of
      these values was noted in the right eye 1 month after Intacs SK implantation,
      which was reversed by CXL. Eight months postoperatively, BSCVA was 20/25 and
      20/25, manifest refractions were -1.50 x 170 and -1.25 x 50, and mean
      keratometric values were 47.20 and 44.20 D in the right and left eyes,
      respectively. CONCLUSIONS: Intacs SK implantation and subsequent CXL may be
      alternatived in the treatment of postoperative LASIK ectasia.

PMID- 18811120
TI  - Staged intrastromal delivery of riboflavin with UVA cross-linking in advanced
      bullous keratopathy: laboratory investigation and first clinical case.
AB  - PURPOSE: To evaluate the safety and efficacy of staged ultraviolet A (UVA) cross
      linking following intrastromal 0.1% riboflavin administration in eyes with
      advanced corneal edema. METHODS: Ten eye bank corneas divided in two groups (n =
      5) were placed on a pressurized artificial anterior chamber following Descemet's
      membrane stripping. Two consecutive corneal pockets (350- and 150-microm depth)
      were sequentially created using a femtosecond laser. Sequential intrastromal
      injections of 0.1% riboflavin (0.2 mL) followed by either UVA irradiation (15
      mW/cm2) for 7 minutes or exposure to air were performed for each pocket. Corneal
      clarity and central thickness were measured before and after the two UVA cross
      linking steps. The same steps were clinically applied in an 84-year-old woman
      with bullous keratopathy prior to corneal transplantation and followed for 6
      months. RESULTS: The corneal clarity improved in the treated but not the control
      eyes. The mean central corneal thickness was significantly reduced by 256 microm
      (ultrasound, P = .0002) and 273 miccrom (Scheimpflug, P = .0004) in treated eyes,
      but only 100 microm (ultrasound, P = .048) and 107 microm (Scheimpflug, P = .075)
      in the control eyes. The clinical treatment of corneal edema showed improved
      clarity and reduced central corneal thickness from 675 to 550 microm (ultrasound)
      and 696 to 571 microm (Scheimpflug) at 1 month. Best spectacle-corrected visual
      acuity improved from finger counting to 20/80 at 1 week and beyond, postponing
      corneal transplantation for > 6 months. CONCLUSIONS: Staged UVA cross-linking (15
      mW/cm2) with femtosecond laser facilitated intrastromal 0.1% riboflavin
      administration may be a safe (no corneal scarring) and effective (marked
      reduction of edema) temporizing alternative method for managing bullous
      keratopathy.

PMID- 18811121
TI  - Cigarette smoking is negatively associated with keratoconus.
AB  - PURPOSE: To investigate a correlation between cigarette smoking and keratoconus.
      METHODS: Patients with keratoconus who were treated with corneal collagen cross
      linking from June 2006 to November 2007 were asked about their smoking habits. A
      person smoking a minimum of two cigarettes per day for more than 1 year was
      classified as a smoker. RESULTS: A total of 180 patients with keratoconus (mean
      age 28 +/- 9 years [range: 15 to 41 years]) were asked about their smoking
      habits. One hundred seventy-one (95%) were non-smokers and only 9 (5%) were
      smokers (95% confidence interval, 2.31 to 9.28). Using the chi-square test, a
      significant correlation was found between non-smokers and keratoconus (P < .001).
      CONCLUSIONS: In this group of patients with keratoconus, few were smokers.
      Cigarette smoke contains toxic substances. Consequently, people are advised not
      to smoke. However, we speculate that the by-products of cigarette smoke may lead
      to cross-linking of collagen, which in the cornea, may prevent the development
      and progression of keratoconus.

PMID- 18811122
TI  - Short chain aliphatic beta-nitro alcohols for corneoscleral cross-linking:
      corneal endothelial toxicity studies.
AB  - PURPOSE: Recent studies suggest that short chain aliphatic beta-nitro alcohols
      can cross-link corneoscleral tissue under physiologic conditions. The present
      study was conducted to determine the cytotoxic threshold for these agents in
      vitro and to draw comparisons to commonly used topical ophthalmic agents.
      METHODS: Primary cultures of bovine corneal endothelial cells were grown to
      confluence in 24- and 96-well plates using standard protocol. The cells were
      exposed to three beta-nitro alcohols, 2-nitroethanol, 2-nitro-1-propanol, and 3
      nitro-2-pentanol in a range of concentrations from 0.1 to 10 mM. After a 48-hour
      exposure, cell necrosis and apoptosis were evaluated using trypan blue, propidium
      iodide, and annexin V staining. In addition, a review of the ophthalmic
      literature was conducted to derive comparisons with agents commonly used in
      clinical practice. RESULTS: An all-or-none response was observed for each
      compound. Positive staining with trypan blue, propidium iodide, and annexin V
      occurred at identical concentrations. The most toxic of the group was 2-nitro-1
      propanol. The cytotoxic level for 2-nitroethanol, 2-nitro-1-propanol, and 3-nitro
      2-pentanol was 3 mM (0.0273%), 1 mM (0.0105%), and 3 mM (0.0399%), respectively.
      Furthermore, by comparison with several agents used in ophthalmic practice such
      as fluoroquinolone antibiotics, anti-proliferative agents, and benzalkonium
      chloride, the beta-nitro alcohols exhibit less toxicity in vitro. CONCLUSIONS:
      Short chain aliphatic beta-nitro alcohols exhibit favorable in vitro toxicity
      thresholds. The result of this study encourages further evaluation of these
      compounds as potential pharmacologic topical stiffening agents for corneoscleral
      disorders.

PMID- 18811123
TI  - Comparative study of riboflavin-UVA cross-linking and "flash-linking" using
      surface wave elastometry.
AB  - PURPOSE: To investigate comparative stiffness values in porcine corneas after
      standard cross-linking and a new, rapid method of cross-linking (flash-linking)
      using surface wave elastometry. METHODS: Ten porcine eyes were treated using an
      ultraviolet A (UVA) double diode light source with a wavelength of 370 nm and
      delivering an irradiance of 4.2 mW/cm2 at a distance of 1.2 cm while applying
      0.1% riboflavin-5-phosphate drops to the central cornea every 5 minutes as a
      photosensitizer for 30 minutes (riboflavin-UVA group). The next 10 porcine
      corneas were treated with a single application of a customized photoactive
      crosslinking agent and 30 seconds of UVA light at the same power and wavelength
      (flash-linking group). Following treatment, the Sonic Eye system (PriaVision Inc)
      was used to measure ultrasound surface wave propagation time between two fixed
      distance transducers applied to the cornea along central horizontal and vertical
      positions. Intraocular pressure was continuously monitored. RESULTS: Mean surface
      wave velocity was determined from the last 5 of 10 sequential measurements for
      each eye, and was 90.87 +/- 15.26 m/s for all eyes with a mean standard deviation
      (SD) of 2.34 m/s among each eye in the riboflavin-UVA group versus 83.66 +/-
      12.30 m/s with a mean SD of 2.69 m/s among each eye in the flash-linking group
      before treatment and 109.2 +/- 21.76 m/s with a mean SD of 2.15 m/s among each
      eye (riboflavin-UVA group) versus 109.2 +/- 18.42 m/s with a mean SD of 2.26 m/s
      among each eye (flash-linking group) after cross-linking. The mean surface wave
      velocity increased by 18.3 units from 90.87 to 109.2 m/s (P = .003) after cross
      linking with riboflavin-UVA, and by 25.5 m/s from 83.66 to 109.2 m/s (P = .0001)
      after flash-linking. Surface wave velocity was noted to increase after both cross
      linking techniques, but the differences observed did not reach statistical
      significance (P = .74). CONCLUSIONS: A new, rapid method of cross-linking (flash
      linking) is introduced by the use of a customized photoactive cross-linking
      agent. The method demonstrates similar efficacy in stiffening the cornea (when
      measured with surface wave elastometry) in comparison to standard cross-linking,
      but requires only 30 seconds of UVA exposure.

PMID- 18811124
TI  - Efficacy and safety of blue-light scleral cross-linking.
AB  - PURPOSE: To evaluate the efficacy of blue-light scleral cross-linking as well as
      its safety in preventing retinal damage beneath the treated sclera. METHODS: Six
      rabbits were unilaterally treated with topical riboflavin (0.5%) and blue light
      (465 nm) on the equatorial sclera using a light emitting diode source with an
      exposure area of 9 mm in diameter. Four weeks after the treatment, the animals
      were euthanized and the exposed sclera and contralateral eye sclera excised for
      comparative testing of biomechanical rigidity and histologic retinal cellular
      damage. Extensiometry was performed to evaluate the stress-strain curve of
      treated versus untreated sclera, and light microscopy of the treated sclera and
      underlying retina were also comparatively evaluated. RESULTS: Blue-light scleral
      cross-linking showed a three-fold increased stiffening in all tested animals in
      the stress-strain curve. Histological investigation revealed no retinal damage in
      any of the treated eyes. CONCLUSIONS: Scleral cross-linking with riboflavin and
      blue light (465 nm) has a stiffening effect on the sclera without histological
      tissue damage to the retina.

PMID- 18811125
TI  - Quantum study of the absorption spectroscopy of bis(triarylamine) radical
      cations.
AB  - Absorption spectra of bridged triarylamine radical cations are calculated quantum
      mechanically which extends our previous classical analysis (Lambert et al. J.
      Phys. Chem. A 2004, 108, 6474). A comparison between spectra determined within a
      diabatic and an adiabatic representation shows that under certain circumstances
      deviations occur. It is found that the latter are mainly caused by the Condon
      approximation for the dipole moments. The inclusion of vibrational degrees of
      freedom leads to an excellent agreement with experiment.

PMID- 18811126
TI  - Spin coupling and resonance.
AB  - The resonating block localize wave function (RBLW) method is introduced, a
      resonating modification of the block localized wave functions introduced by Mo et
      al. [Mo, Y.; Peyerimhoff, S. D. J. Chem. Phys. 1998, 109, 1687].This approach
      allows the evaluation of resonance energies following Pauling's recipe. The
      method is tested on two model molecules, hexagonal H(6) and benzene. Calculations
      have been done with (local) and without local restrictions (delocal). Resonance
      energies for both molecules have been obtained for each type of calculation, in
      agreement with Pauling's concept. From a comparison of the resonance energies
      obtained from RBLW and standard valence bond calculations, the resonating block
      localize wave functions prove to yield resonance energies close to standard
      valence bond delocal calculations.

PMID- 18811127
TI  - Dependence of charge-transport parameters on static correlation and self
      interaction energy: the case of a 1,4-bis(phenylethynyl)benzene derivative
      conjugated molecule.
AB  - The current research on molecular-based devices built with highly unsaturated
      molecules is largely assisted by computational techniques. These modern
      computational tools are intended to serve (i) to understand the relation between
      the mechanism of charge transport and the chemical composition of the
      semiconductors and (ii) to perform the molecular engineering needed to design new
      and more efficient organic materials. We have studied the case of a rod-shaped
      conjugated molecule widely used in molecular electronics. The results of
      multireference perturbation theory up to second order (MRMP2) and complete active
      space self-consistent field calculations (CASSCF) are compared with the results
      provided by energy density functionals. Motivated by the diverse accuracy of the
      results depending on the theoretical method selected, we have systematically
      studied the physical origin of the discrepancies. We find that a subtle interplay
      between correlation effects and the self-interaction energy mainly governs the
      results, which makes it thus difficult to anticipate the quality of a method
      without knowing in advance its dependence on both effects. We thus encourage
      careful testing of computational methods for the rational design and
      understanding of conjugated materials for charge conduits.

PMID- 18811128
TI  - HfO2:X (X = Eu(3+), Ce(3+), Y(3+)) sol gel powders for ultradense scintillating
      materials.
AB  - Hafnium dioxide (HfO 2) presents a high crystalline density which makes it
      attractive for host lattice activated by rare earths for applications as
      scintillating materials. HfO 2 powders doped with Eu (3+) or Ce (3+) luminescent
      ions are prepared by sol gel process. The annealing temperature and the
      concentration of doping ions are optimized to provide the powder presenting the
      best scintillation yield. The powders are crystallized in monoclinic phase
      whatever annealing temperature above 800 degrees C. The emission spectra are
      characterized by a white broadband between 400 and 600 nm. After optimization,
      the most efficient composition, namely HfO 2:2.5% Eu 1% Y (molar percent)
      exhibits a scintillation yield about 31,000 photons/MeV, which is about 3.8 times
      that of the standard Bi 3Ge 5O 12 (BGO) commercial powder.

PMID- 18811129
TI  - Ab initio study of intriguing coordination complexes: a metal field theory
      picture.
AB  - Two noninnocent ligands are theoretically studied using wave function based
      methods to demonstrate their ability to undergo singlet-triplet transition under
      the effect of an external charge mimicking the electrostatic role of a metal ion.
      It is shown that the singlet-triplet energy difference is very sensitive to the
      metal ion charge which tunes the HOMO-LUMO energy difference of these ligands.
      While the latter is reduced as the charge is enhanced in the glyoxal-bis-(2
      mercaptoanil) (gma) ligand, it is increased in the bis(imino)pyridine diradical
      ligand. This result shows a strong analogy with the crystal field theory,
      interchanging the roles played by the metal ion and the ligand. As the metal ion
      is explicitly treated in the Fe(gma)CN complex, this analogy can be pushed
      further resulting in a "metal field theory" conceptualization.

PMID- 18811130
TI  - Spectroscopic and computational studies of (mu-oxo)(mu-1,2-peroxo)diiron(III)
      complexes of relevance to nonheme diiron oxygenase intermediates.
AB  - With the goal of gaining insight into the structures of peroxo intermediates
      observed for oxygen-activating nonheme diiron enzymes, a series of metastable
      synthetic diiron(III)-peroxo complexes with [Fe(III)(2)(mu-O)(mu-1,2-O(2))] cores
      has been characterized by X-ray absorption and resonance Raman spectroscopies,
      EXAFS analysis shows that this basic core structure gives rise to an Fe-Fe
      distance of approximately 3.15 A; the distance is decreased by 0.1 A upon
      introduction of an additional carboxylate bridge. In corresponding resonance
      Raman studies, vibrations arising from both the Fe-O-Fe and the Fe-O-O-Fe units
      can be observed. Importantly a linear correlation can be discerned between the
      nu(O-O) frequency of a complex and its Fe-Fe distance among the subset of
      complexes with [Fe(III)(2)(mu-OR)(mu-1,2-O(2))] cores (R = H, alkyl, aryl, or no
      substituent). These experimental studies are complemented by a normal coordinate
      analysis and DFT calculations.

PMID- 18811131
TI  - Interaction of hydronium ion with dibenzo-18-crown-6: NMR, IR, and theoretical
      study.
AB  - Interaction of dibenzo-18-crown-6 (DBC) with H 3O (+) (HP) in nitrobenzene- d 5
      and dichloromethane- d 2 was studied by using (1)H and (13)C NMR spectra and
      relaxations, FTIR spectra, and quantum chemical DFT calculations. NMR shows that
      the DBC*HP complex is in a dynamic equilibrium with the reactants, the
      equilibrium constant K being 0.66 x 10 (3), 1.16 x 10 (4), and 1.03 x 10 (4) L x
      mol (-1) in CD 2Cl 2, nitrobenzene, and acetonitrile, respectively. The complex
      appears to have a C 2 v symmetry in NMR, but FTIR combined with DFT normal mode
      calculations suggest that such high symmetry is only apparent and due to exchange
      averaging of the structure. FTIR spectra as well as energy-optimized DFT
      calculations show that the most stable state of the complex in solution is that
      with three linear hydrogen bonds of HP with one CH 2-O-CH 2 and two Ar-O-Ar
      oxygen atoms. The structure is similar to that found in solid state but adopts a
      somewhat different conformation in solution. The dynamics of exchange between
      bound and free DBC was studied by NMR transverse relaxation. It was found to be
      too fast to give reproducible results when measured with the ordinary CPMG
      sequence or its variant DIFTRE removing residual static dipolar interaction, but
      it could be established by rotating-frame measurements with high intensity of the
      spin-lock field. The correlation time of exchange was found to be 5.6 x 10 (-6)
      and 3.8 x 10 (-6) s in dichloromethane and nitrobenzene, respectively. Such fast
      exchange can be explained by cooperative assistance of present water molecules.

PMID- 18811133
TI  - Structure-activity studies on a series of a 2-aminopyrimidine-containing
      histamine H4 receptor ligands.
AB  - A series of 2-aminopyrimidines was synthesized as ligands of the histamine H4
      receptor (H4R). Working in part from a pyrimidine hit that was identified in an
      HTS campaign, SAR studies were carried out to optimize the potency, which led to
      compound 3, 4- tert-butyl-6-(4-methylpiperazin-1-yl)pyrimidin-2-ylamine. We
      further studied this compound by systematically modifying the core pyrimidine
      moiety, the methylpiperazine at position 4, the NH2 at position 2, and positions
      5 and 6 of the pyrimidine ring. The pyrimidine 6 position benefited the most from
      this optimization, especially in analogs in which the 6- tert-butyl was replaced
      with aromatic and secondary amine moieties. The highlight of the optimization
      campaign was compound 4, 4-[2-amino-6-(4-methylpiperazin-1-yl)pyrimidin-4
      yl]benzonitrile, which was potent in vitro and was active as an anti-inflammatory
      agent in an animal model and had antinociceptive activity in a pain model, which
      supports the potential of H 4R antagonists in pain.

PMID- 18811132
TI  - Toward optimization of the linker substructure common to transthyretin
      amyloidogenesis inhibitors using biochemical and structural studies.
AB  - To develop potent and highly selective transthyretin (TTR) amyloidogenesis
      inhibitors, it is useful to systematically optimize the three substructural
      elements that compose a typical TTR kinetic stabilizer: the two aryl rings and
      the linker joining them. Herein, we evaluated 40 bisaryl molecules based on 10
      unique linker substructures to determine how these linkages influence inhibitor
      potency and selectivity. These linkers connect one unsubstituted aromatic ring to
      either a 3,5-X 2 or a 3,5-X 2-4-OH phenyl substructure (X = Br or CH 3).
      Coconsideration of amyloid inhibition and ex vivo plasma TTR binding selectivity
      data reveal that direct connection of the two aryls or linkage through nonpolar E
      olefin or -CH 2CH 2- substructures generates the most potent and selective TTR
      amyloidogenesis inhibitors exhibiting minimal undesirable binding to the thyroid
      hormone nuclear receptor or the COX-1 enzyme. Five high-resolution TTR.inhibitor
      crystal structures (1.4-1.8 A) provide insight into why such linkers afford
      inhibitors with greater potency and selectivity.

PMID- 18811134
TI  - Discovery of bioavailable 4,4-disubstituted piperidines as potent ligands of the
      chemokine receptor 5 and inhibitors of the human immunodeficiency virus-1.
AB  - We describe robust chemical approaches toward putative CCR5 scaffolds designed in
      our laboratories. Evaluation of analogues in the (125)I-[MIP-1beta] binding and
      Ba-L-HOS antiviral assays resulted in the discovery of 64 and 68 in the 4,4
      disubstitited piperidine class H, both potent CCR5 ligands (pIC 50 = 8.30 and
      9.00, respectively) and HIV-1 inhibitors (pIC 50 = 7.80 and 7.84, respectively,
      in Ba-L-HOS assay). In addition, 64 and 68 were bioavailable in rodents,
      establishing them as lead molecules for further optimization toward CCR5 clinical
      candidates.

PMID- 18811135
TI  - Identification of a nonbasic, nitrile-containing cathepsin K inhibitor (MK-1256)
      that is efficacious in a monkey model of osteoporosis.
AB  - Herein, we report on the identification of nonbasic, potent, and highly
      selective, nitrile-containing cathepsin K (Cat K) inhibitors that are built on
      our previously identified cyclohexanecarboxamide core structure. Subsequent to
      our initial investigations, we have found that incorporation of five-membered
      heterocycles as P2-P3 linkers allowed for the introduction of a methyl sulfone P3
      substitutent that was not tolerated in inhibitors containing a six-membered
      aromatic P2-P3 linker. The combination of a five-membered N-methylpyrazole linker
      and a methyl sulfone in P3 yielded subnanomolar Cat K inhibitors that were
      minimally shifted (<10-fold) in our functional bone resorption assay. Issues that
      arose because of metabolic demethylation of the N-methylpyrazole were addressed
      through introduction of a 2,2,2-trifluoroethyl substituent. This culminated in
      the identification of 31 (MK-1256), a potent (Cat K IC 50 = 0.62 nM) and
      selective (>1100-fold selectivity vs Cat B, L, S, C, H, Z, and V, 110-fold vs Cat
      F) inhibitor of cathepsin K that is efficacious in a monkey model of
      osteoporosis.

PMID- 18811136
TI  - Alpha,beta-methylene-2'-deoxynucleoside 5'-triphosphates as noncleavable
      substrates for DNA polymerases: isolation, characterization, and stability
      studies of novel 2'-deoxycyclonucleosides, 3,5'-cyclo-dG, and 2,5'-cyclo-dT.
AB  - We report synthesis and characterization of a complete set of alpha,beta
      methylene-2'-dNTPs (alpha,beta-m-dNTP; N = A, C, T, G, 12-15) in which the
      alpha,beta-oxygen linkage of natural dNTP was replaced by a methylene group.
      These nucleotides were designed to be noncleavable substrates for DNA
      polymerases. Synthesis entails preparation of 2'-deoxynucleoside 5'-diphosphate
      precursors, followed by an enzymatic gamma-phosphorylation. All four synthesized
      alpha,beta-m-dNTPs were found to be potent inhibitors of polymerase beta, with K
      i values ranging 1-5 microM. During preparation of the dG and dT derivatives of
      alpha,beta-methylene diphosphate, we also isolated significant amounts of 3,5'
      cyclo-dG (16) and 2,5'-cyclo-dT (17), respectively. These novel 2'
      deoxycyclonucleosides were formed via a base-catalyzed intramolecular cyclization
      (N3 --> C5' and O2 --> C5', respectively). In acidic solution, both 16 and 17
      underwent glycolysis, followed by complete depurination. When exposed to alkaline
      conditions, 16 underwent an oxidative deamination to produce 3,5'- cyclo-2'
      deoxyxanthosine (19), whereas 17 was hydrolyzed exclusively to dT.

PMID- 18811137
TI  - Modified peptides as potent inhibitors of the postsynaptic density-95/N-methyl-D
      aspartate receptor interaction.
AB  - The protein-protein interaction between the NMDA receptor and its intracellular
      scaffolding protein, PSD-95, is a potential target for treatment of ischemic
      brain diseases. An undecapeptide corresponding to the C-terminal of the NMDA was
      used as a template for finding lead candidates for the inhibition of the PSD
      95/NMDA receptor interaction. Initially, truncation and alanine scan studies were
      carried out, which resulted in a pentapeptide with wild-type affinity, as
      examined in a fluorescence polarization assay. Further examination was performed
      by systematic substitutions with natural and unnatural amino acids, which
      disclosed a tripeptide with micromolar affinity and N-methylated tetrapeptides
      with improved affinities. Molecular modeling studies guided further N-terminal
      modifications and introduction of a range of N-terminal substitutions
      dramatically improved affinity. The best compound, N-cyclohexylethyl-ETAV (56),
      demonstrated up to 19-fold lower K i value ( K i = 0.94 and 0.45 microM against
      PDZ1 and PDZ2 of PSD-95, respectively) compared to wild-type values, providing
      the most potent inhibitors of this interaction reported so far. These novel and
      potent inhibitors provide an important basis for development of small molecule
      inhibitors of the PSD-95/NMDA receptor interaction.

PMID- 18811138
TI  - Structure-activity relationships of truncated D- and l-4'-thioadenosine
      derivatives as species-independent A3 adenosine receptor antagonists.
AB  - Novel D- and l-4'-thioadenosine derivatives lacking the 4'-hydroxymethyl moiety
      were synthesized, starting from d-mannose and d-gulonic gamma-lactone,
      respectively, as potent and selective species-independent A 3 adenosine receptor
      (AR) antagonists. Among the novel 4'-truncated 2-H nucleosides tested, a N(6)-(3
      chlorobenzyl) derivative 7c was the most potent at the human A 3 AR (K i = 1.5
      nM), but a N(6)-(3-bromobenzyl) derivative 7d showed the optimal species
      independent binding affinity.

PMID- 18811139
TI  - 1H-cyclopentapyrimidine-2,4(1H,3H)-dione-related ionotropic glutamate receptors
      ligands. structure-activity relationships and identification of potent and
      Selective iGluR5 modulators.
AB  - (S)-CPW399 ((S)-1) is a potent and excitotoxic AMPA receptor partial agonist.
      Modifying the cyclopentane ring of (S)-1, we developed two of the most potent and
      selective functional antagonists (5 and 7) for kainate receptor (KA-R) subunit
      iGluR5. Derivatives 5 and 7, with their unique pharmacological profile, may lead
      to a better understanding of the different roles and modes of action of iGluR1-5
      subunits, paving the way for the synthesis of new potent, subunit selective
      iGluR5 modulators.

PMID- 18811140
TI  - Discovery and X-ray crystallographic analysis of a spiropiperidine iminohydantoin
      inhibitor of beta-secretase.
AB  - A high-throughput screen at 100 microM inhibitor concentration for the BACE-1
      enzyme revealed a novel spiropiperidine iminohydantoin aspartyl protease
      inhibitor template. An X-ray cocrystal structure with BACE-1 revealed a novel
      mode of binding whereby the inhibitor interacts with the catalytic aspartates via
      bridging water molecules. Using the crystal structure as a guide, potent
      compounds with good brain penetration were designed.

PMID- 18811142
TI  - Preparation and upconversion luminescence of three-dimensionally ordered
      macroporous ZrO2: Er3+, Yb3+.
AB  - The three-dimensionally ordered macroporous (3DOM) ZrO2: Er(3+), Yb(3+) materials
      were successfully synthesized by the sol-gel method combined with a polystyrene
      latex sphere templating technique, and their morphologies, surface
      physicochemical properties, and upconversion photoluminescence (UC-PL) properties
      were studied. The results indicate that the materials exhibited both porosity and
      strong UC-PL under the excitation of a 978 nm diode laser. In comparison with the
      nonporous samples, the relative intensity of the red ((4)F(9/2)-(4)I(15/2)) to
      the green ((4)S(3/2)/(2)H(11/2)-(4)I(15/2)) emission decreased visibly because of
      the decreased nonradiative relaxation in the 3DOM materials. It was also observed
      that the relative intensity of the green emission to the red emission increased
      significantly with the increasing excitation power. An indirect three-photon
      populating process occurred for the green emission as the excitation power and
      Yb(3+) concentration was high enough.

PMID- 18811143
TI  - Theoretical studies on the redox potentials of Fe dinuclear complexes as models
      for hydrogenase.
AB  - Density Functional calculations have been performed at the uB3LYP and uBP86
      levels to calculate the one-electron redox potentials for a series of small
      models based on the diiron hydrogenase enzymes in the presence of acetonitrile
      (MeCN). The solvation effects in MeCN are incorporated via a self-consistent
      reaction field (SCRF) using the polarized continuum model (PCM). The calculated
      redox potentials reproduce the trends in experimental data with an average error
      of only 0.12 V using the BP86 functional, whereas comparing results with the
      B3LYP functional require a systematic shift of -0.82 and -0.53 V for oxidation
      and reduction, respectively. The bonding orbitals and d-electron populations were
      examined using Mulliken population analysis, and the results were used to
      rationalize the calculated and observed redox potentials. These studies
      demonstrate that the redox potential correlates with the empirical
      spectrochemical series for the ligands, as well as with the amount of electron
      density donated by the ligand onto the Fe centers.

PMID- 18811144
TI  - Polygallide RE2MGa9Ge2 (RE = Ce, Sm; M = Ni, Co) phases grown in molten gallium.
AB  - The quaternary intermetallics Ce2CoGa9Ge2, Ce2NiGa9Ge2, and Sm2NiGa9Ge2 were
      prepared by reacting elemental metals in excess of gallium at 850 degrees C. The
      title compounds crystallize in the tetragonal space group P4/nmm in the
      Sm2Ni(Si(1-x)Ni(x))Al4Si6 structure type with cell parameters a = 5.9582(5) A, c
      = 15.0137(18) A, and a = 5.9082(17) A, c = 14.919(6) A, Z = 2, for Ce2CoGa9Ge2
      and Sm2NiGa9Ge2, respectively. The structures are composed of covalently bonded
      three-dimensional networks of [CoGa9Ge2] in which the rare-earth metals fill the
      voids forming a 2D square net. The structures of RE2MGa9Ge2 are Ga-rich and
      possess extensive Ga-Ga bonding even though the Ga atoms do not form a network on
      their own. Magnetic susceptibility measurements for Ce2CoGa9Ge2 and Ce2NiGa9Ge2
      show Curie-Weiss paramagnetism, consistent with presence of Ce(3+) ions.
      Magnetocrystalline anisotropy was observed for Ce2NiGa9Ge2, with the magnetically
      easy axis lying along the [001] crystallographic direction. A transition to an
      antiferromagnetic state was observed below 4 K in the easy direction of
      magnetization. In the magnetically hard direction of the basal plane,
      paramagnetic behavior was observed down to 1.8 K.

PMID- 18811145
TI  - Hydrothermal synthesis, structures, and physical properties of four new flexible
      multicarboxylate ligands-based compounds.
AB  - Four new compounds of partially or wholly deprotonated 5,5'-(1,4
      phenylenebis(methylene))bis(oxy)diisophthalic acid (H4L1) and 5,5'-(1,3
      phenylenebis(methylene))bis(oxy)diisophthalic acid (H4L2), namely {[Co(L1)0.5] x
      (H2O)2}n (1), {[Mn(L1)0.5] x (H2O)2}n (2), {[Cu(H2L1)](mu2-bipy)}n (bipy = 4, 4'
      bipyridyl) (3), and {[Zn2(L2)] x H2O}n (4) were synthesized in the presence or
      absence of auxiliary bipy ligand. Their structures have been determined by single
      crystal X-ray diffraction analysis and further characterized by elemental
      analysis, IR spectra, and thermogravimetric analysis. Compounds 1 and 2 are
      isostructural and possess three-dimensional (3D) networks. In compound 3,
      multicarboxylate ligands and bipy ligands link Cu centers to generate a two
      dimensional (2D) sheet structure which is further connected by intermolecular
      hydrogen bonds to form a 3D supramolecular structure. In compound 4, the Zn
      centers are connected by L2(4-) anions to generate a 3D framework. Magnetic
      susceptibility measurements indicate that compounds 1 and 2 exhibit
      antiferromagnetic coupling between adjacent Co(II) ions and Mn(II) ions. The
      photoluminescent properties of the free 4L1 and H4L2 ligands and compound 4 have
      been studied in the solid state at room temperature. Both ligands and compound 4
      exhibit strong violet emissions. Compared with the fluorescent emission of the
      ligand, the emission of 4 is red-shifted and enhanced.

PMID- 18811146
TI  - Sn(x)Pt4Sn(y)Sb(12-y): a skutterudite with covalently bonded filler.
AB  - A new phase, Sn(x)Pt4Sb(12-y)Sn(y), has been prepared from the elements. It
      exhibits a wide range of homogeneity with 0.3(2) < or = x < or = 1.0(2) and
      4.2(2) < or = y < or = 7.0(2). The crystal structure and the composition were
      established by single-crystal and powder X-ray diffraction as well as wavelength
      dispersive X-ray analysis measurements and were supported by nuclear magnetic
      resonance experiments. The compound is the first representative of the filled
      skutterudite family with the filler atoms not located at the center of the cavity
      but covalently bonded to the cavity's wall, as confirmed by the analysis of
      chemical bonding with the electron localizability indicator. The Sn and Sb atoms
      share the framework site with different coordinate parameters caused by the
      difference in atomic size; additional tin atoms are located in the cavities of
      the framework. The material is a diamagnet in the whole composition range. In
      agreement with the calculated electronic density of states, the material reveals
      a metallic behavior in electronic transport. The absolute values of electrical
      resistivity vary with the tin-to-antimony ratio.

PMID- 18811147
TI  - Multimetallic assemblies using piperazine-based dithiocarbamate building blocks.
AB  - Treatment of cis-[RuCl2(dppm)2] (dppm = bis(diphenylphosphino)methane) with
      dithiocarbamates, NaS2CNR2 (R = Me, Et) and [H2NC5H10][S2CNC5H10], yields cations
      [Ru(S2CNR2)2(dppm)2](+) and [Ru(S2CNC5H10)2(dppm)2](+), respectively. The
      zwitterions S2CNC4H8NHR (R = Me, Et) react with the same metal complex in the
      presence of base to yield [Ru(S2CNC4H8NR)(dppm)2](+). Piperazine or 2,6
      dimethylpiperazine reacts with carbon disulfide to give the zwitterionic
      dithiocarbamate salts H2NC4H6(R2-3,5)NCS2 (R = H; R = Me), which form the
      complexes [Ru(S2CNC4H6(R2-3,5)NH2)(dppm)2](2+) on reaction with cis
      [RuCl2(dppm)2]. Sequential treatment of [Ru(S2CNC4H8NH2)(dppm)2](2+) with
      triethylamine and carbon disulfide forms the versatile metalla-dithiocarbamate
      complex [Ru(S2CNC4H8NCS2)(dppm)2] which reacts readily with cis-[RuCl2(dppm)2] to
      yield [{Ru(dppm)2}2(S2CNC4H8NCS2)]. Reaction of [Ru(S2CNC4H8NCS2)(dppm)2] with
      [Os(CH=CHC6H4Me-4)Cl(CO)(BTD)(PPh3)2] (BTD = 2,1,3-benzothiadiazole),
      [Pd(C6H4CH2NMe2)Cl]2, [PtCl2(PEt3)2], and [NiCl2(dppp)] (dppp = 1,3
      bis(diphenylphosphino)propane) results in the heterobimetallic complexes
      [(dppm)2Ru(S2CNC4H8NCS2)ML(n))](m+) (ML(n) = Os(CH=CHC6H4Me-4)(CO)(PPh3)2](+), m
      = 1; ML(n) = Pd(C,N-C6H4CH2NMe2), m = 1; ML(n) = Pt(PEt3)2, m = 2; ML(n) =
      Ni(dppp), m = 2). Reaction of [NiCl2(dppp)] with H2NC4H8NCS2 yields the
      structurally characterized compound, [Ni(S2CNC4H8NH2)(dppp)](2+), which reacts
      with base, CS2, and cis-[RuCl2(dppm)2] to provide an alternative route to
      [(dppm)2Ru(S2CNC4H8NCS2)Ni(dppp)](+). A further metalla-dithiocarbamate based on
      cobalt, [CpCo(S2CNC4H8NH2)(PPh3)](2+), is formed by treatment of CpCoI2(CO) with
      S2CNC4H8NH2 followed by PPh3. Further reaction with NEt3, CS2, and cis
      [RuCl2(dppm)2] yields [(Ph3P)CpCo(S2CNC4H8NCS2)Ru(dppm)2](2+). Heterotrimetallic
      species of the form [{(dppm)2Ru(S2CNC4H8NCS2)}2M](2+) result from the reaction of
      [Ru(S2CNC4H8NCS2)(dppm)2] and M(OAc)2 (where M = Ni, Cu, Zn). Reaction of
      [Ru(S2CNC4H8NCS2)(dppm)2] with Co(acac)3 and LaCl3 results in the formation of
      the compounds [{(dppm)2Ru(S2CNC4H8NCS2)}3Co](3+) and
      [{(dppm)2Ru(S2CNC4H8NCS2)}3La](3+), respectively. The electrochemical behavior of
      selected examples is also reported.

PMID- 18811148
TI  - Highly selective phosphorescent chemosensor for fluoride based on an iridium(III)
      complex containing arylborane units.
AB  - A new phosphorescent iridium(III) complex [Ir(Bpq)2(bpy)](+)PF6(-) based on
      cyclometalated ligands (Bpq) containing a dimesitylboryl group was synthesized
      and characterized by photophysical and electrochemical studies. The excited-state
      properties of Bpq and [Ir(Bpq)2(bpy)](+)PF6(-) were investigated using molecular
      orbital calculations. Importantly, both Bpq and [Ir(Bpq)2(bpy)](+)PF6(-) could be
      used as highly selective chemosensors for a fluoride anion (F(-)) detected by the
      naked eye, owing to the interaction of the dimesitylboryl group (BMes2) with F(
      ). For the Bpq ligand, a red shift of the emission spectrum was observed upon the
      addition of F(-), which could be attributed to an excited-state switch from a pi
      pi* transition to a charge-transfer transition upon complexation with F(-). The
      addition of F(-) to a solution of [Ir(Bpq)2(bpy)](+)PF6(-) induced a change in
      the solution color from yellow to orange-red and phosphorescent quenching,
      indicating that [Ir(Bpq)2(bpy)](+)PF6(-) could act as an excellent ON-OFF-type
      phosphorescent chemosensor for F(-).

PMID- 18811149
TI  - An open-framework thorium sulfate hydrate with 11.5 A voids.
AB  - We report the synthesis of a thorium sulfate hydrate with 11.5 A open channels
      that propagate through the structure. The compound crystallizes in the tetragonal
      space group P4(2)/nmc, a = b = 25.890(4) A, c = 9.080(2) A, Z = 8, V = 6086.3(2)
      A(3). The thermal stability of the compound was investigated using
      thermogravimetric analysis and high-energy X-ray scattering (HEXS) revealing that
      the compound begins to undergo decomposition near 200 degrees C with an
      accompanied loss in crystallinity. The immediate coordination environment about
      the thorium atoms remains intact through heating to 500 degrees C as demonstrated
      by HEXS. Further heating reveals the formation of at least two crystalline
      phases, Th(SO4)2 and ThO2, which ultimately decompose to ThO2.

PMID- 18811150
TI  - DNA-binding and physical studies of Pt(4'-NR2-trpy)CN+ systems (trpy =
      2,2':6',2''-terpyridine).
AB  - This paper focuses on DNA-binding interactions exhibited by Pt(dma-T)CN(+), where
      dma-T denotes 4'-dimethylamino-2,2':6',2''-terpyridine, and includes
      complementary studies of the corresponding pyrr-T complex, where pyrr-T denotes
      4'-(N-pyrrolidinyl)-2,2':6',2''-terpyridine. The chromophores are useful for
      understanding the interesting and rather intricate DNA-binding interactions
      exhibited by these and related systems. One reason is that the terpyridine
      ligands employed provide intense visible absorption and enhanced
      photoluminescence signals. Incorporating cyanide as a coligand further aids
      analysis by suppressing covalent binding. Physical methods utilized include X-ray
      crystallography for structures of the individual inorganic complexes. Viscometry
      as well as spectral studies of the absorbance, emission, and circular dichroism
      (CD) yield information about interactions with a variety of DNA hosts. Although
      there is no sign of covalent binding under the conditions used, most hosts
      exhibit two phases of uptake. Under conditions of high loading (low base-pair-to
      platinum ratios), the dma-T complex preferentially binds externally and
      aggregates on the surface of the host, except for the comparatively rigid host
      [poly(dG-dC)]2. Characteristic signs of the aggregated form include a bisignate
      CD signal in the charge-transfer region of the spectrum and strongly
      bathochromically shifted emission. When excess DNA is present, however, the
      complex shifts to intercalative binding, preferentially next to G[triple bond]C
      base pairs if available. Once the complex internalizes into DNA it becomes
      virtually immune to quenching by O2 or solvent, and the emission lifetime extends
      to 11 micros when [poly(dI-dC)]2 is the host. On the other hand, the host itself
      becomes a potent quenching agent when G[triple bond]C base pairs are present
      because of the reducing strength of guanine residues.

PMID- 18811151
TI  - Amidolithium and amidoaluminum catalyzed synthesis of substituted guanidines: an
      interplay of DFT modeling and experiment.
AB  - The synthesis of substituted guanidines is of significant interest for their use
      as versatile ligands and for the synthesis of bioactive molecules. Lithium amides
      supported by tetramethylethylenediamine have recently been shown to catalyze the
      guanylation of amines with carbodiimide. In this report, density functional
      theory (DFT) calculations are used to provide insight into the mechanism of this
      transformation. The mechanism identified through our calculations is a
      carbodiimide insertion into the lithium-amide bond to form a lithium guanidinate,
      followed by a proton transfer from the amine. The proton transfer transition
      state requires the dissociation of one of the chelating nitrogen centers of the
      lithium guanidinate, proton abstraction from the amine, and bond formation
      between the lithium center and the amine nitrogen. On the basis of this
      mechanism, further calculations predicted that aluminum amides would also
      function as active catalysts for the guanylation of amines. We confirm this
      experimentally and report the development of aluminum amides as a new main group
      catalyst for the guanylation of a range of electron-poor amines with
      carbodiimide.

PMID- 18811152
TI  - Modeling of the various minima on the potential energy surface of bispidine
      copper(II) complexes: a further test for ligand field molecular mechanics.
AB  - Copper(II) complexes of bispidines (bispidine = tetra-, penta-, or hexadentate
      ligand, based on the 3,7-diazabicyclo[3.3.1]nonane backbone) display several
      isomeric forms. Depending on the substitution pattern of the bispidine and the
      type of coligands used, the structure elongates along one of the three potential
      Jahn-Teller axes. In an effort to develop a computational tool which can predict
      which isomer is observed, 23 bispidine-copper(II) complexes with 19 different
      ligands are analyzed theoretically by ligand field molecular mechanics (LFMM).
      With two exceptions, the lowest-energy LFMM structure and the experimental solid
      state structure agree concerning the Jahn-Teller axis. However, in most cases and
      especially for six-coordinate complexes, LFMM predicts a second local minimum
      within a few kilojoules per mole. Although detailed analysis reveals that the
      current force field is too "stiff", reasonable quantitative reproduction of the
      structural data is achieved with Cu-L bond length root mean square (rms)
      deviations for nine complexes of 0.05 A or less and with 20 reproduced to a rms
      deviation of 0.1 A or less. Across all of the complexes, the Cu-amine and Cu
      pyridyl bond length rms deviations are 0.07 and 0.12 A, respectively.

PMID- 18811153
TI  - Novel heterometallic Fe-Ru2-Fe arrays via "complex of complexes" approach.
AB  - Four tetranuclear heterometallic compounds, [(Tp)Fe(CN)3]2[Ru2(DMBA)4] (1),
      [(MeTp)Fe(CN)3]2[Ru2(DMBA)4] (2), [((i)BuTp)Fe(CN)3]2[Ru2(DMBA)4] (3), and
      [(PhTp)Fe(CN)3]2[Ru2(DMBA)4] (4) [DMBA = N,N'-dimethylbenzamidinate, Tp =
      (hydrotris(pyrazolyl)borate, MeTp = (methyltris(pyrazolyl)borate, (i)BuTp = (2
      methylpropyltris(pyrazolyl)borate, and PhTp = (tris(pyrazolyl)phenylborate)] were
      prepared from the combination of Ru2(DMBA)4(NO3)2 and an appropriate
      [(RTp)Fe(CN)3](-). Molecular structures of compounds 1-4 were established using
      single-crystal X-ray diffraction, and all feature a linear Fe-C[triple bond]N-Ru
      Ru-N[triple bond]C-Fe array. The magnetic study revealed that the temperature
      dependence of chi(M)T is mostly attributed to the zero-field splitting of the Ru2
      center, indicating the absence of strong spin coupling among three metallic
      centers. The electronic independence was further confirmed by the vis-NIR
      spectroscopic studies. Also described are the voltammetric properties of these
      compounds.

PMID- 18811154
TI  - Preparation, separation, and characterization of ruthenium(II) thiocyanate
      linkage isomers.
AB  - The reaction of [(p-cym)Ru(bpy)Cl](+) (p-cym = eta(6)-p-cymene; bpy = 2,2'
      bipyridine) with SCN(-) gives a mixture of the linkage isomers [(p
      cym)Ru(bpy)(SCN)](+) and [(p-cym)Ru(bpy)(NCS)](+). The linkage isomers were
      efficiently separated by column chromatography on Hg(NO3)2-coated Al2O3. Both
      isomers were fully characterized by elemental analysis, (1)H NMR and IR
      spectroscopy, and X-ray crystallography. The equilibrium constant for the
      conversion of the S-bound to the N-bound isomer was determined to be 0.29(4) in
      methanol-d4 and 0.74(7) in acetone-d6, respectively, at 50 degrees C. Kinetic
      data for the linkage isomerization reaction are also reported.

PMID- 18811156
TI  - Enhanced activity for oxygen reduction reaction on "Pt3Co" nanoparticles: direct
      evidence of percolated and sandwich-segregation structures.
AB  - Atomically resolved structures and compositions of Pt alloy nanoparticles were
      obtained using aberration-corrected high-angle dark field imaging, which was
      correlated to specific ORR activity based on a Pt surface area. The enhanced
      specific ORR activity (approximately 2 times relative to Pt) of acid-treated
      "Pt3Co" nanoparticles can be related to composition variations at the atomic
      scale and the formation of percolated Pt-rich and Pt-poor regions within
      individual particles. Upon annealing, we show direct evidence of surface Pt
      sandwich-segregation structures, which correspond to a specific ORR activity
      approximately 4 times relative to Pt.

PMID- 18811157
TI  - Deeper insight into the mechanism of the reaction of photogenerated
      metallaketenes and imines.
AB  - The reaction mechanism between Fischer carbene complexes and imines to produce
      beta-lactams has been studied by a combination of computational (DFT) and
      experimental methodologies. After the photogeneration of metalla-cyclopropanone
      species, the reaction initiates by 1,3-migration of the metal fragment from the
      former carbene carbon atom to the oxygen in the S o hypersurface. In spite of the
      endothermic nature of this rearrangement, it is biased by the more favorable
      HOMO(imine)-LUMO+1 interaction in the oxygen-coordinated ketene. This species
      reacts with the imine to yield metalla-zwitterions, which form the final products
      through a four electron conrotatory ring closure. The presence of the metal
      moiety during the whole reaction coordinate is demonstrated by the use of a
      chiral chromium(0) alkoxycarbene complex, which produces low but significant ee
      in the reaction with imines. The cis-trans stereoselection derives from the
      nucleophilic addition of the nitrogen atom of the imine to the oxygen-coordinated
      ketene, since there are no significant differences between the classical and the
      metallated processes in the electrocyclation step leading to the final 2
      azetidinones.

PMID- 18811158
TI  - Bcl-XL-templated assembly of its own protein-protein interaction modulator from
      fragments decorated with thio acids and sulfonyl azides.
AB  - Protein-protein interactions have key importance in various biological processes
      and modulation of particular protein-protein interactions has been shown to have
      therapeutic effects. However, disrupting or modulating protein-protein
      interactions with low-molecular-weight compounds is extremely difficult due to
      the lack of deep binding pockets on protein surfaces. Herein we describe the
      development of an unprecedented lead synthesis and discovery method that
      generates only biologically active compounds from a library of reactive
      fragments. Using the protein Bcl-XL, a central regulator of programmed cell
      death, we demonstrated that an amidation reaction between thio acids and sulfonyl
      azides is applicable for Bcl-XL-templated assembly of inhibitory compounds. We
      have demonstrated for the first time that kinetic target-guided synthesis can be
      applied not only on enzymatic targets but also for the discovery of small
      molecules modulating protein-protein interactions.

PMID- 18811159
TI  - Stoichiometric zirconium oxide cations as potential building blocks for cluster
      assembled catalysts.
AB  - Employing guided-ion-beam mass spectrometry, we identified a series of positively
      charged stoichiometric zirconium oxide clusters that exhibit enhanced activity
      and selectivity for three oxidation reactions of widespread chemical importance.
      Density functional theory calculations reveal that these clusters all contain the
      same active site consisting of a radical oxygen center with an elongated
      zirconium-oxygen bond. Calculated energy profiles demonstrate that each oxidation
      reaction is highly favorable energetically and involves easily surmountable
      barriers. Furthermore, the active stoichiometric clusters may be regenerated by
      reacting oxygen-deficient clusters with a strong oxidizer. This indicates that
      these species may promote multiple cycles of oxidation reactions and, therefore,
      exhibit true catalytic behavior. The stoichiometric clusters, having structures
      that resemble specific sites in bulk zirconia, are promising candidates for
      potential incorporation into a cluster assembled catalyst material.

PMID- 18811160
TI  - The unfolded ensemble and folding mechanism of the C-terminal GB1 beta-hairpin.
AB  - In this work, we shed new light on a much-studied case of beta-hairpin folding by
      means of advanced molecular dynamics simulations. A fully atomistic description
      of the protein and the solvent molecule is used, together with metadynamics, to
      accelerate the sampling and estimate free-energy landscapes. This is achieved
      using the path collective variables approach, which provides an adaptive
      description of the mechanism under study. We discover that the folding mechanism
      is a multiscale process where the turn region conformation leads to two different
      energy pathways that are connected by elongated structures. The former displays a
      stable 2:4 native-like structure in which an optimal hydrophobic packing and
      hydrogen bond pattern leads to 8 kcal/mol of stabilization. The latter shows a
      less-structured 3:5 beta-sheet, where hydrogen bonds and hydrophobic packing
      provide only 2.5 kcal/mol of stability. This perspective is fully consistent with
      experimental evidence that shows this to be a prototypical two-state folder,
      while it redefines the nature of the unfolded state.

PMID- 18811161
TI  - Palladium-catalyzed amination of aryl and heteroaryl tosylates at room
      temperature.
AB  - Mild palladium-catalyzed aminations of aryl tosylates and the first aminations of
      heteroaryl tosylates are described. In the presence of the combination of L2Pd(0)
      (L = P(o-tol)3) and the hindered Josiphos ligand CyPF-t-Bu, a variety of primary
      alkylamines and arylamines react with both aryl and heteroaryl tosylates at room
      temperature to form the corresponding secondary arylamines in high yields with
      complete selectivity for the monoarylamine. These reactions at room temperature
      occur in many cases with catalyst loadings of 0.1 mol % and 0.01 mol % in one
      case, constituting the most efficient aminations of aryl tosylates by nearly 2
      orders of magnitude. This catalyst is made practical by the development of a
      convenient method to synthesize the L2Pd(0) precursor. This complex is stable to
      air as a solid. In contrast to conventional relative rates for reactions of aryl
      sulfonates, the reactions of aryl tosylates are faster than parallel reactions of
      aryl triflates, and the reactions of aryl tosylates are faster than parallel or
      competitive reactions of aryl chlorides.

PMID- 18811162
TI  - Acid promoted cinnamyl ion mobility within peptide derived macrocycles.
AB  - We are developing methods that restrict the conformational mobility of peptides
      and related heteropolymers while simultaneously altering their properties. Our
      experiments occur as processes wherein a conserved, lipophilic reagent is
      activated in stages to form composite products with unprotected polyamides in
      parallel. For each starting oligomer, the goal is to create not one, but rather a
      collection of products. The intent is for those materials to retain molecular
      recognition elements of the biopolymer, yet display that functionality as part of
      stable, cyclic structures having defined shapes and enhanced membrane
      solubility/permeability. Here we describe reagent 2 and its two-step integration
      into peptides to afford macrocyclic ethers (e.g., 4 when starting with W-W-Y).
      When those materials are treated with protic acid in anhydrous solvent, the
      cinnamyl unit migrates from the oxygen of tyrosine to distribute throughout the
      structure, forming new products via carbon/carbon bonding. These changes occur
      concomitantly with acid-promoted rearrangements/cyclizations of the dienyne
      appendage to generate mixtures containing unique macrocycles such as 15. Similar
      amalgamations of 2 with more diverse peptides is a means to begin accessing
      complex peptidomimetics systematically. From a library of screening fractions
      generated in this way, we have identified a small molecule that selectively
      promotes hippocampal neurogenesis in the adult mouse brain.

PMID- 18811163
TI  - Charge-transfer and spin dynamics in DNA hairpin conjugates with perylenediimide
      as a base-pair surrogate.
AB  - A perylenediimide chromophore (P) was incorporated into DNA hairpins as a base
      pair surrogate to prevent the self-aggregation of P that is typical when it is
      used as the hairpin linker. The photoinduced charge-transfer and spin dynamics of
      these hairpins were studied using femtosecond transient absorption spectroscopy
      and time-resolved EPR spectroscopy (TREPR). P is a photooxidant that is
      sufficiently powerful to quantitatively inject holes into adjacent adenine (A)
      and guanine (G) nucleobases. The charge-transfer dynamics observed following hole
      injection from P into the A-tract of the DNA hairpins is consistent with
      formation of a polaron involving an estimated 3-4 A bases. Trapping of the (A 3
      4) (+*) polaron by a G base at the opposite end of the A-tract from P is
      competitive with charge recombination of the polaron and P (-*) only at short P-G
      distances. In a hairpin having 3 A-T base pairs between P and G ( 4G), the
      radical ion pair that results from trapping of the hole by G is spin-correlated
      and displays TREPR spectra at 295 and 85 K that are consistent with its formation
      from (1*)P by the radical-pair intersystem crossing mechanism. Charge
      recombination is spin-selective and produces (3*)P, which at 85 K exhibits a spin
      polarized TREPR spectrum that is diagnostic of its origin from the spin
      correlated radical ion pair. Interestingly, in a hairpin having no G bases ( 0G),
      TREPR spectra at 85 K revealed a spin-correlated radical pair with a dipolar
      interaction identical to that of 4G, implying that the A-base in the fourth A-T
      base pair away from the P chromophore serves as a hole trap. Our data suggest
      that hole injection and transport in these hairpins is completely dominated by
      polaron generation and movement to a trap site rather than by superexchange. On
      the other hand, the barrier for charge injection from G (+*) back onto the A-T
      base pairs is strongly activated, so charge recombination from G (or even A trap
      sites at 85 K) most likely proceeds by a superexchange mechanism.

PMID- 18811164
TI  - Light-induced excited-state spin trapping in tetrazole-based spin crossover
      systems.
AB  - Ab initio calculations have been performed on Fe (II) (tz) 6 (tz = 1- H
      tetrazole) to establish the variation of the energy of the electronic states
      relevant to (reverse) light-induced excited-state spin trapping (LIESST) as
      function of the Fe-ligand distance. Equilibrium distances and absorption energies
      are correctly reproduced. The deactivation of the excited singlet is proposed to
      occur in the Franck-Condon region through overlap of vibrational states with an
      intermediate triplet state or an intersystem crossing along an asymmetric
      vibrational mode. This is followed by an intersystem crossing with the quintet
      state. Reverse LIESST involves a quintet-triplet and a triplet-singlet
      intersystem crossing around the equilibrium distance of the high-spin state. The
      influence of the transition metal is studied by changing Fe (II) for Co (II), Co
      (III), and Fe (III). The calculated curves for Fe (III) show remarkable
      similarity with Fe (II), indicating that the LIESST mechanism is based on the
      same electronic conversions in both systems.

PMID- 18811165
TI  - An extraordinary cylinder-to-cylinder transition in the aqueous assemblies of
      fluorescently labeled rod-coil amphiphiles.
AB  - We report an unprecedented cylinder-to-cylinder transformation in the self
      assemblies of pyrene-labeled rod-coil molecules in water. The extraordinary
      morphological transformation can be monitored by a fluorescence variation from
      exciplex to excimer emissions, suggesting the rod-packing transition from
      antiparallel to interdigitated arrangements as a function of PEO coil length.

PMID- 18811166
TI  - Isolation of anacardic acid from natural cashew nut shell liquid (CNSL) using
      supercritical carbon dioxide.
AB  - Solvent extracted cashew nut shell liquid (CNSL), conventionally known as natural
      CNSL, is a mixture of several alkenyl phenols. One of these alkenyl phenols is
      anacardic acid, which is present at the highest concentration. In view of
      anticipated industrial applications of anacardic acid, the objective of this work
      was to isolate anacardic acid from natural CNSL by supercritical carbon dioxide
      (scCO 2). In this study, the solubility data for natural CNSL in scCO 2 under a
      range of operating conditions of pressure (100, 200, and 300 bar), temperature
      (40 and 50 degrees C), and CO 2 flow rate (5, 10, and 15 g min (-1)) were
      established. The best scCO 2 working conditions were found to be 50 degrees C and
      300 bar at a flow rate of 5 g min (-1) CO 2. Using 3 g of sample (CNSL/solid
      adsorbent = 1/2) under these scCO 2 conditions, it was possible to quantitatively
      isolate high purity anacardic acid from crude natural CNSL (82% of total
      anacardic acid) within 150 min. The anacardic acid isolated by scCO 2 was
      analyzed by different spectroscopic techniques (UV-vis, FT-IR, and (1)H NMR) and
      HPLC analysis, indicating that the anacardic acid isolated by scCO 2 has better
      quality than that obtained through a conventional method involving several
      chemical conversion steps.

PMID- 18811167
TI  - Factors affecting thermally induced furan formation.
AB  - Furan, a potential carcinogen, can be induced by heat from sugars, ascorbic acid,
      and fatty acids. The objective of this research was to investigate the effect of
      pH, phosphate, temperature, and heating time on furan formation. Heat-induced
      furan formation from free sugars, ascorbic acid, and linoleic acid was profoundly
      affected by pH and the presence of phosphate. In general, the presence of
      phosphate increased furan formation in solutions of sugars and ascorbic acid. In
      a linoleic acid emulsion, phosphate increased the formation of furan at pH 6 but
      not at pH 3. When an ascorbic acid solution was heated, higher amounts of furan
      were produced at pH 3 than at pH 6 regardless of phosphate's presence. However,
      in linoleic acid emulsion, more furan was produced at pH 6 than at pH 3. The
      highest amount of furan was formed from the linoleic acid emulsion at pH 6. In
      fresh apple cider, a product with free sugars as the major components (besides
      water) and little fatty acids, ascorbic acid, or phosphate, small or very low
      amounts of furan was formed by heating at 90-120 degrees C for up to 10 min. The
      results indicated that free sugars may not lead to significant amounts of furan
      formation under conditions for pasteurization and sterilization. Importantly,
      this is the first report demonstrating that phosphate (in addition to pH) plays a
      significant role in thermally induced furan formation.

PMID- 18811168
TI  - Emission of volatile chemicals from flowering dogwood (cornus Florida L.)
      flowers.
AB  - Reproduction of flowering dogwood trees occurs via obligate out-crossing, and
      U.S. native bees have been suggested to be primary pollinators of this
      ecologically and economically important deciduous tree. Whether floral volatiles
      play a role in reproduction of the dogwood remains unclear. Objectives of this
      study were to identify principal volatile chemicals emitted from dogwood flowers
      and to assess a temporal volatile emission profile and volatile consistency
      across four cultivars. Inflorescences with intact bracts and 5 cm flower pedicel
      were removed from dogwood trees and subjected to headspace volatile collection.
      Six principal volatile compounds were detected from the flowers of the cultivar
      'World's Fair' with 3-formylpyridine as the most abundant constituent. Subsequent
      headspace analyses performed using inflorescences without bracts or floral
      pedicels alone indicated that 3-formylpyridine, E-beta-ocimene, S-linalool, and
      ketoisophorone were mainly emitted from inflorescences. Experiments were also
      conducted to determine whether volatile emissions differed across time and
      between different cultivars of flowering dogwood. When volatile emission was
      analyzed for 48 h using 12 h light/dark cycles, the emission of several volatile
      compounds displayed diurnal patterns. Finally, whereas florets in inflorescences
      of four different dogwood cultivars emitted similar levels of the six principal
      floral volatile chemicals, 'Cherokee Brave' flowers alone yielded 4
      methoxybenzaldehyde and germacrene-D. The implications of the findings of this
      study to dogwood breeding programs are discussed.

PMID- 18811169
TI  - Olfactory perception of cysteine-S-conjugates from fruits and vegetables.
AB  - Volatile sulfur compounds have a low odor threshold, and their presence at
      microgram per kilogram levels in fruits and vegetables influences odor quality.
      Sensory analysis demonstrates that naturally occurring, odorless cysteine- S
      conjugates such as S-( R/ S)-3-(1-hexanol)- l-cysteine in wine, S-(1-propyl)- l
      cysteine in onion, and S-(( R/ S)-2-heptyl)- l-cysteine in bell pepper are
      transformed into volatile thiols in the mouth by microflora. The time delay in
      smelling these volatile thiols was 20-30 s, and persistent perception of their
      odor occurred for 3 min. The cysteine- S-conjugates are transformed in free thiol
      by anaerobes. The mouth acts as a reactor, adding another dimension to odor
      perception, and saliva modulates flavors by trapping free thiols.

PMID- 18811170
TI  - Highly enantioselective hydroformylation of aryl alkenes with diazaphospholane
      ligands.
AB  - Asymmetric, rhodium-catalyzed hydroformylation of terminal and internal aryl
      alkenes with diazaphospholane ligands is reported. Under partially optimized
      reaction conditions, high enantioselectivity (>90% ee) and regioselectivities (up
      to 65:1 alpha:beta) are obtained for most substrates. For terminal alkenes, both
      enantioselectivity and regioselectivity are proportional to the carbon monoxide
      partial pressure, but independent of hydrogen pressure. Hydroformylation of para
      substituted styrene derivatives gives the highest regioselectivity for substrates
      bearing electron-withdrawing substituents. A Hammett analysis produces a positive
      linear correlation for regioselectivity.

PMID- 18811171
TI  - Total synthesis of amphidinolide J.
AB  - The marine natural product amphidinolide J has been synthesized according to a
      convergent strategy. The key steps of this synthesis include a B-alkyl Suzuki
      Miyaura coupling and the addition of an alkynyllithium reagent to a Weinreb amide
      to build the C4-C5 and C12-C13 bonds, respectively, and a Yamaguchi
      macrolactonization.

PMID- 18811172
TI  - 2-Hydroxy-5-nitrobenzyl as a diazeniumdiolate protecting group: application in NO
      releasing polymers with enhanced biocompatibility.
AB  - The 2-hydroxy-5-nitrobenzyl group is shown to be an effective protecting group
      for diazeniumdiolates. O(2)-(2-hydroxy-5-nitrobenzyl)-substituted
      diazeniumdiolates display enhanced thermal stability, but efficiently release
      nitric oxide (NO) in pH 7.4 aqueous solutions. A lipophilic analogue incorporated
      into hydrophobic polymers shows NO surface flux rates comparable to that of the
      natural endothelium. Importantly, these polymer formulations also show
      significantly enhanced biocompatibility in vivo with use of a porcine implant
      model.

PMID- 18811173
TI  - Synthesis of the C1-C12 fragment of iriomoteolide 1a by sequential catalytic
      asymmetric vinylogous aldol reactions.
AB  - An efficient synthesis of the C1-C12 fragment of iriomoteolide 1a has been
      accomplished via sequential application of two catalytic, asymmetric, vinylogous
      aldol reactions: a catalytic vinylogous aldol reaction was used to
      enantioselectively introduce the C5-C8 segment, and a second catalytic vinylogous
      aldol reaction was used to install the remaining two stereocenters and a
      stereodefined alkene in the form of an alpha,beta-unsaturated delta-lactone in
      one step.

PMID- 18811174
TI  - Hydrogenation of hindered ketones catalyzed by a silica-supported compact
      phosphine-Rh system.
AB  - A heterogeneous mono(phosphine)-Rh catalyst system silica-SMAP-Rh(OMe)(cod),
      where silica-SMAP stands for a caged, compact trialkylphosphine (SMAP) supported
      on silica gel, showed broad applicability toward the hydrogenation of hindered
      ketones. Doubly alpha-branched ketones such as diisopropyl ketone was
      hydrogenated under nearly atmospheric conditions. Di-tert-butyl ketone could be
      hydrogenated under more forcing conditions.

PMID- 18811175
TI  - A convenient Negishi protocol for the synthesis of glycosylated
      oligo(ethynylene)s.
AB  - A convenient and efficient sp-sp carbon heterocoupling protocol based on the
      Negishi reaction was developed, in which the required zinc diacetylide was
      generated from 1,4-bis(trimethylsilyl)butadiyne in situ and reacted with a
      bromoacetylene in apolar solvent mixtures. The method has been applied to the
      synthesis of unsymmetric glycosylated and symmetric diglycosylated
      oligo(ethynylene)s up to the octa(ethynylene).

PMID- 18811176
TI  - Palladium-catalyzed direct arylation of nitro-substituted aromatics with aryl
      halides.
AB  - Direct arylation reactions of nitrobenzenes and aryl halides occur in good yield
      and high ortho regioselectivity. These reactions can be performed on gram scale
      with as few as 3 equiv of the nitro arene relative to the aryl halide. The
      synthetic utility of this method is demonstrated via rapid synthesis of a
      Boscalid intermediate.

PMID- 18811177
TI  - A tandem one-pot, microwave-assisted synthesis of regiochemically differentiated
      1,2,4,5-tetrahydro-1,4-benzodiazepin-3-ones.
AB  - A one-pot, two-step synthesis of the title compounds employs a multicomponent Ugi
      condensation reaction, microwave irradiation, and Fe(0) as a reductant. Two
      pathways are accessible; both routes utilize bifunctional, o-nitro-substituted
      arenes leading to either C2, N4, C5 substitution (A) or C2, N4 substitution (B).

PMID- 18811178
TI  - Asymmetric, organocatalytic, three-step synthesis of gamma-hydroxy-(E)-alpha,beta
      unsaturated sulfones and esters.
AB  - Efficient and enantiocontrolled synthesis of gamma-hydroxy-alpha,beta-unsaturated
      sulfones and esters are reported through the reaction of enantioenriched alpha
      selenyl aldehydes with EWG-stabilized carbanions and then a one-pot selenide
      oxidation, in situ epoxide formation, and final in situ epoxide opening.

PMID- 18811180
TI  - Identification of unknowns in atmospheric pressure ionization mass spectrometry
      using a mass to structure search engine.
AB  - This study evaluates a new model for identifying unknown compounds in atmospheric
      pressure ionization mass spectrometry based on a mass-to-structure (MTS)
      paradigm. In this method, rudimentary ESI spectrum interpretation is required to
      recognize key spectral features such as MH (+), MNa (+), and MNH 4 (+), which
      lead to the unknown's monoisotopic mass. The unknown's mass is associated
      directly with known organic compounds using an Access 2003 database containing
      records of 19,438 substances assembled from common sources such as the Merck
      Index, pesticide and pharmaceutical compilations, and chemical catalogues. A user
      defined mass tolerance (+/-0.001-0.5 Da) is set according to the instrument mass
      accuracyunit mass resolution data require a wide mass tolerance ( approximately
      0.5 Da) while tolerances for accurate mass data can be as narrow as +/-0.001 Da.
      Candidate structures retrieved with the MTS Search Engine appear in a report
      window providing formulas, mass error, and Internet links. This paper provides
      examples of structure elucidation with 15 organic compounds based on ESI mass
      spectra from both unit mass resolution (e.g., quadrupole ion trap and triple
      stage quadrupole) and accurate mass instruments (e.g., TOF and Q-TOF). Orthogonal
      information (e.g., isotope ratios and fragmentation data) is complementary and
      useful for ranking candidates and confirming assignments. The MTS Search Engine
      identifies unknowns quickly and efficiently, and supplements existing
      interpretation schemes for unknown identification.

PMID- 18811181
TI  - Reversible photoinduced electron transfer in a ruthenium poly(2-methoxyaniline-5
      sulfonic acid) composite film.
AB  - In situ electron spin resonance (ESR) studies have been performed on composite
      films consisting of a ruthenium tris(bipyridyl) complex and an inherently
      conducting polymer, poly(2-methoxyaniline-5-sulfonic acid) (PMAS). The composites
      were investigated under white light irradiation and potential control conditions
      to probe photoinduced electron transfer between the ruthenium metal center and
      the conducting polymer. PMAS exhibited a clear ESR signal, characteristic of the
      presence of mobile single spin polarons within the polymer structure. Irradiation
      of the PMAS in the presence of the ruthenium metal center resulted in the photo
      oxidation of the Ru (2+) to the Ru (3+) state, as a result of which the PMAS ESR
      signal was replaced by a response typical of the Ru (3+) salt. Upon removal of
      the illumination, reversible photo switching occurred. This reversibility makes
      these novel composites promising for applications in areas such as chemical
      sensors, light switching, and light harvesting devices.

PMID- 18811182
TI  - Structure and speciation in hydrous silica melts. 1. Temperature and composition
      effects.
AB  - Monte Carlo simulations were used to investigate the phase behavior of hydrated
      liquid silica as a function of temperature and overall water mole fraction, x w.
      Simulations using the Feuston-Garofalini potential were performed in the isobaric
      isothermal ensemble at p = 1 GPa for 15 temperatures (2000 < or = T < or = 9000
      K) and 25 compositions (0.0 < or = x w < or = 0.4). The unusual volume minimum
      exhibited by tetrahedrally coordinated liquid silica is found to persist up to x
      w approximately 0.267, although the temperature of the volume minimum decreases
      with increasing water content. Structural properties of the pure and hydrated
      systems are compared and the addition of water to liquid silica disrupts the
      silica network more dramatically than temperature alone. The simulations yield
      very low concentrations of molecular water, e.g. only about 1.2% of the oxygen
      atoms are bound to exactly two hydrogen atoms at x w = 0.4 and T = 3000 K.

PMID- 18811183
TI  - Quantum chemical calculations of the redox potential of the Pu(VII)/Pu(VIII)
      couple.
AB  - The redox potential of the Pu(VII)/Pu(VIII) couple was studied by density
      functional theory calculations. The spin-orbit effect was corrected at the CASSCF
      level. The redox potential (relative to the standard hydrogen potential) of the
      Pu(VII)/Pu(VIII) couple in alkaline solution was found to vary from 4.36 to 1.06
      V depending on the number of Pu-O oxo bonds, coordination numbers, and
      coordination modes. The redox potential drops substantially as the number of Pu-O
      oxo bonds increases. Pu(VIII) may be synthesized in strong alkaline solution
      assuming that both Pu(VII) and Pu(VIII) exist in penta-oxo form, Pu (VII)O 5OH (4
      ) and Pu (VIII)O 5OH (3-), respectively. The Mulliken population of Pu in Pu(VII)
      and Pu(VIII) complexes are very similar, suggesting that the spin-orbit effect is
      rather small in Pu(VII) complexes and that when Pu(VII) is oxidized to Pu(VIII)
      the electron is stripped mainly from the ligand. Consequently, Pu(VIII) is in an
      unstable oxidation state and easily reduced back to Pu(VII) by the solvent water
      molecules. In acidic medium, the Pu(VII)/Pu(VIII) redox potential is too high to
      get the Pu(VIII) valence state.

PMID- 18811184
TI  - Structure and speciation in hydrous silica melts. 2. Pressure effects.
AB  - The effect of pressure on structure and water speciation in hydrated liquid
      silica is examined over a range of temperatures and compositions. The Feuston
      Garofalini (FG) potential is used in isobaric-isothermal Monte Carlo simulations
      carried out at four pressures (0.25, 1.0, 2.5, and 10 GPa) for seven temperatures
      (2000 < or = T < or= 9000 K) and five compositions (0.0 < or = x_w < or = 0.4).
      The FG potential yields a stable melt phase for p > or = 1.0 GPa and/or x_w < or
      = 0.1 for all temperatures. The volume minimum seen in previous simulations of
      pure and hydrated liquid silica using the FG potential persists up to 2.5 GPa but
      is no longer evident at 10 GPa. This is correlated with gradual structural
      changes of the liquid up to 2.5 GPa and with more significant changes at 10 GPa.
      Even at high overall concentrations of water (x_w = 0.4), only about 2% of oxygen
      atoms are present as molecular water species at the lowest temperature. This
      percentage decreases with increasing pressure and temperature.

PMID- 18811186
TI  - Surfactant and hydrocarbon aggregates on defective graphite surface: structure
      and dynamics.
AB  - We have simulated the structure and aggregation kinetics of sodium dodecyl
      sulfate (SDS) and dodecane (C 12) on a graphite surface in the presence of point
      and line defects. We find that while vacancies do not affect the orientational
      bias of the molecules, they interfere with aggregate formation. Specifically,
      they disrupt the formation of extended aggregates. Line defects in the form of
      surface steps, on the other hand, tend to localize the aggregates in their
      vicinity and induce specific orientations along the step edges. We demonstrate
      that this orientational bias can be tuned by manipulating the terrace widths.
      These results suggest that extended defects could be employed to localize and
      orient surfactant aggregates on the basal plane of graphite, thus providing a
      means to create patterned aggregate domains.

PMID- 18811187
TI  - New insights into urea action on proteins: a SANS study of the lysozyme case.
AB  - We present a study on lysozyme dissolved in mixtures of water and urea, which is
      ubiquitously used as a protein denaturant. Despite the wide use of urea, the
      basic molecular mechanisms inducing protein unfolding are not still clarified.
      Small-angle neutron scattering (SANS) experiments have been performed using
      little amounts of denaturant in solutions in order to investigate the urea effect
      on lysozyme preceding the unfolding process. A global fit strategy, applied to
      analyze SANS experiments, provides an estimation of the average composition of
      the solvent in the close vicinity of the protein surface and the change of the
      protein-protein interactions due to the presence of urea. In particular, the
      thermodynamic equilibrium constant responsible for cosolvent balancing between
      the bulk and solvation layer has been determined. It turns out that urea is
      preferentially driven to the protein surface, confirming literature results at
      infinite dilute conditions. SANS data also reveal a possible variation of the
      protein net charge as a function of urea concentration, opening new perspectives
      and questions about the protein surface architecture at the first stages of
      unfolding processes.

PMID- 18811188
TI  - Solvation of phenylglycine- and leucine-derived chiral stationary phases:
      molecular dynamics simulation study.
AB  - A theoretical study of the solvation of ( R)- N-(3,5-dinitrobenzoyl)phenylglycine
      and ( R)- N-(3,5-dinitrobenzoyl)leucine-derived chiral stationary phases (CSPs)
      is presented. Semiflexible models of the chiral selectors are prepared from
      B3LYP/6-311G** calculations, and these are used in the molecular dynamics
      simulations of the corresponding interface. The chiral interface is examined for
      four solvents: 100% hexane, 90:10 hexane:2-propanol, 80:20 hexane:2-propanol, and
      100% 2-propanol. Despite the similarities between phenylglycine and leucine, the
      interfaces are distinct both in terms of the selector orientations at the surface
      and in the number of hydrogen bonds formed with 2-propanol. We also find that an
      increase in alcohol concentration alters the preferred orientations of the
      selectors.

PMID- 18811189
TI  - An unexpected phase transition during the [2 + 2] photocycloaddition reaction of
      cinnamic acid to truxillic acid: changes in polymorphism monitored by solid-state
      NMR.
AB  - We have detected a phase transition during the progress of the solid-state [2 +
      2] photocycloaddition reaction of alpha-trans-cinnamic acid. The reaction was
      monitored using (13)C CPMAS experiments as a function of irradiation time of the
      parent alpha-trans-cinnamic acid, which forms the product dimer, alpha-truxillic
      acid. UV light centered at 350 nm was used for photoirradiation, which is in the
      "tail" of the absorption band of cinnamic acid. Two different crystal polymorphs
      of alpha-truxillic acid are observed (P2(1)/n and C2/c) at different stages of
      conversion of the parent crystal, assigned through (13)C NMR and powder X-ray
      diffraction. The two polymorphs showed clear, distinguishable patterns in the
      (13)C NMR spectra: a 2-peak versus 3-peak pattern corresponding to sites on the 4
      membered sp (3) hybridized ring in the photoproduct. A phase transition is
      observed midway through the reaction, which we have assigned to the conversion of
      the P2(1)/n polymorph to the C2/ c polymorph of alpha-truxillic acid. The packing
      energy of the resultant mixed crystal of cinnamic acid and truxillic acid changes
      during the course of the photoreaction, which allows for the C2/c polymorph of
      truxillic acid to appear. Both phases have been confirmed via X-ray powder
      diffraction. Two techniques--differential scanning calorimetry and solid-state
      CPMAS NMR using increasingly fast rotational frequencies--demonstrate that the
      P2(1)/n phase is metastable.

PMID- 18811190
TI  - Structural analysis of a beta-helical protein motif stabilized by targeted
      replacements with conformationally constrained amino acids.
AB  - Here we study conformational stabilization induced in a beta-helical
      nanostructure by position-specific mutations. The nanostructure is constructed
      through the self-assembly of the beta-helical building block excised from E. coli
      galactoside acetyltransferase (PDB code 1krr , chain A; residues 131-165). The
      mutations involve substitutions by cyclic, conformationally constrained amino
      acids. Specifically, a complete structural analysis of the Pro-Xaa-Val sequence
      [with Xaa being Gly, Ac 3c (1-aminocyclopropane-1-carboxylic acid) and Ac 5c (1
      aminocyclopentane-1-carboxylic acid)], corresponding to the 148-150 loop region
      in the wild-type (Gly) and mutated (Ac 3c and Ac 5c) 1krr , has been performed
      using Molecular Dynamics simulations and X-ray crystallography. Simulations have
      been performed for the wild-type and mutants of three different systems, namely
      the building block, the nanoconstruct and the isolated Pro-Xaa-Val tripeptide.
      Furthermore, the crystalline structures of five peptides of Pro-Xaa-Val or Xaa
      Val sequences have been solved by X-ray diffraction analysis and compared with
      theoretical predictions. Both the theoretical and crystallographic studies
      indicate that the Pro-Ac n c-Val sequences exhibit a high propensity to adopt
      turn-like conformations, and this propensity is little affected by the chemical
      environment. Overall, the results indicate that replacement of Gly149 by Ac 3c or
      Ac 5c significantly reduce the conformational flexibility of the target site
      enhancing the structural specificity of the building block and the nanoconstruct
      derived from the 1krr beta-helical motif.

PMID- 18811191
TI  - Dynamic mechanism of fatty acid transport across cellular membranes through FadL:
      molecular dynamics simulations.
AB  - FadL is an important member of the family of fatty acid transport proteins within
      membranes. In this study, 11 conventional molecular dynamics (CMD) and 25 steered
      molecular dynamics (SMD) simulations were performed to investigate the dynamic
      mechanism of transport of long-chain fatty acids (LCFAs) across FadL. The CMD
      simulations addressed the intrinsically dynamic behavior of FadL. Both the CMD
      and SMD simulations revealed that a fatty acid molecule can move diffusively to a
      high-affinity site (HAS) from a low-affinity site (LAS). During this process, the
      swing motion of the L3 segment and the hydrophobic interaction between the fatty
      acid and FadL could play important roles. Furthermore, 22 of the SMD simulations
      revealed that fatty acids can pass through the gap between the hatch domain and
      the transmembrane domain (TMD) by different pathways. SMD simulations identified
      nine possible pathways for dodecanoic acid (DA) threading the barrel of FadL. The
      binding free energy profiles between DA and FadL along the MD trajectories
      indicate that all of the possible pathways are energetically favorable for the
      transport of fatty acids; however, one pathway (path VI) might be the most
      probable pathway for DA transport. The reasonability and reliability of this
      study were further demonstrated by correlating the MD simulation results with the
      available mutagenesis results. On the basis of the simulations, a mechanism for
      the full-length transport process of DA from the extracellular side to the
      periplasmic space mediated by FadL is proposed.

PMID- 18811192
TI  - Assignment of polarization-dependent peaks in carbon K-edge spectra from biogenic
      and geologic aragonite.
AB  - Many biominerals, including mollusk and echinoderm shells, avian eggshells,
      modern and fossil bacterial sediments, planktonic coccolithophores, and
      foraminifera, contain carbonates in the form of biogenic aragonite or calcite.
      Here we analyze biogenic and geologic aragonite using different kinds of surface-
      and bulk-sensitive X-ray absorption near-edge structure (XANES) spectroscopy at
      the carbon K-edge, as well as high-resolution scanning transmission X-ray
      microscopy (STXM). Besides the well-known main pi* and sigma* carbonate peaks, we
      observed and fully characterized four minor peaks, at energies between the main
      pi* and sigma* peaks. As expected, the main peaks are similar in geologic and
      biogenic aragonite, while the minor peaks differ in relative intensity. In this
      and previous work, the minor peaks appear to be the ones most affected in
      biomineralization processes, hence the interest in characterizing them. Peak
      assignment was achieved by correlation of polarization-dependent behavior of the
      minor peaks with that of the main pi* and sigma* peaks. The present
      characterization provides the background for future studies of aragonitic
      biominerals.

PMID- 18811193
TI  - Static dielectric constant of room temperature ionic liquids: internal pressure
      and cohesive energy density approach.
AB  - Measurements of the static dielectric constant (epsilon) of ionic liquids (ILs)
      are very difficult because of the decay of field by the ionic conductivity of
      ILs. Herein, we describe an easy method for the prediction of epsilon of various
      imidazolium-based ILs [C_n mim] from n, i.e. the ratio of internal pressure (P_i)
      and cohesive energy density (ced). A calibration curve of n vs epsilon for
      conventional organic solvents (mainly the linear alcohols) has been used to
      estimate the epsilon of the ILs. Estimated epsilon values for ILs having the
      anions [Cl]-, [BF 4]-, [PF 6]-, [TfO]-, and [Tf 2N]- showed a very good
      comparison with the literature results, whereas ILs having the anions [C_n OSO3]-
      tend to deviate from such correlation. Also, for a series of ILs having a common
      anion, the epsilon is shown to follow a very good correlation with the molecular
      volumes. Predicted values show that both the nature of the anion and alkyl chain
      length of the cation contribute significantly to the epsilon of the ILs. The
      method developed makes use of properties which can be either experimentally
      determined or estimated with good accuracy and can be extended to the other
      categories of ILs with ease and reasonable accuracy.

PMID- 18811194
TI  - A quantum mechanical/molecular mechanical study on the catalysis of the pyridoxal
      5'-phosphate-dependent enzyme L-serine dehydratase.
AB  - The catalytic mechanism of a pyridoxal 5'-phosphate-dependent enzyme, l-serine
      dehydratase, has been investigated using ab initio quantum mechanical/molecular
      mechanical (QM/MM) methods. New insights into the chemical steps have been
      obtained, including the chemical role of the substrate carboxyl group in the
      Schiff base formation step and a proton-relaying mechanism involving the
      phosphate of the cofactor in the beta-hydroxyl-leaving step. The latter step is
      of no barrier and follows sequentially after the elimination of the alpha-proton,
      leading to a single but sequential alpha, beta-elimination step. The rate
      limiting transition state is specifically stabilized by the enzyme environment.
      At this transition state, charges are localized on the substrate carboxyl group,
      as well as on the amino group of Lys41. Specific interactions of the enzyme
      environment with these groups are able to lower the activation barrier
      significantly. One major difficulty associated with studies of complicated
      enzymatic reactions using ab initio QM/MM models is the appropriate choices of
      reaction coordinates. In this study, we have made use of efficient semiempirical
      models and pathway optimization techniques to overcome this difficulty.

PMID- 18811195
TI  - Helix-coil transition of a four-way DNA junction observed by multiple
      fluorescence parameters.
AB  - The thermal denaturation of immobile four-way DNA ("Holliday-") junctions with 17
      base pair arms was studied via fluorescence spectroscopic measurements. Two arms
      of the molecule were labeled at the 5'-end with fluorescein and
      tetramethylrhodamine, respectively. Melting was monitored by the fluorescence
      intensity of the dyes, the fluorescence anisotropy of tetramethylrhodamine, and
      Forster resonance energy transfer (FRET) between fluorescein and rhodamine. To
      fit the thermal denaturation curves of the four-way junctions, two basic
      thermodynamic models were tested: (1) all-or-none transitions assuming a
      molecularity of one, two, or four and (2) a statistical "zipper" model. The all
      or-none models correspond to reaction mechanisms assuming that the cooperative
      melting unit (that is, the structure changing from complete helix to complete
      coil) consists of (1) one arm, (2) two neighboring arms (which have one
      continuous strand common to the two arms), or (3) all four arms. In each case,
      the melting of the cooperative unit takes place in a single step. The
      tetramolecular reaction model (four-arm melting) yielded unrealistically low
      van't Hoff enthalpy and entropy values, whereas the monomolecular model (one-arm
      melting) resulted in a poor fit to the experimental data. The all-or-none
      bimolecular (two neighboring arm model) fit gave intermediate standard enthalpy
      change (Delta H) values between those expected for the melting of a duplex with a
      total length between the helix lengths of one and two arms (17 and 34 base
      pairs). Simulations according to the zipper model fit the experimental curves
      best when the length of the simulated duplex was assumed to be 34 base pairs, the
      length of a single strand. This suggests that the most important parameter
      determining the melting behavior of the molecule is the end-to-end distance of
      the strands (34 bases) rather than the length of the individual arms (17 base
      pairs) and that the equilibrium concentration of partially denatured intermediate
      states has to be taken into account. These findings are in good agreement with
      results obtained for three-way DNA junctions ( Stuhmeier, F. ; Lilley, D. M. ;
      Clegg, R. M. Biochemistry 1997, 36, 13539 ). An interesting result is that the
      extent-of-melting curves derived from the fluorescence intensity and anisotropy
      nearly agree, whereas the curve derived from the FRET data shows a change prior
      to the melting. This may be an indication of a conformational change leaving the
      double-stranded structure intact but changing the end-to-end distance of the
      different arms in a way consistent with the transition to the extended square
      configuration ( Clegg, R. M. ; Murchie, A. I. ; Lilley, D. M. Biophys. J. 1994,
      66, 99 ) of this branched molecule.

PMID- 18811196
TI  - Diffusion-viscosity decoupling in supercooled aqueous trehalose solutions.
AB  - The diffusional mobility of disodium fluorescein has been measured in supercooled
      aqueous solutions of trehalose, a widely used cryoprotectant disaccharide. The
      results were analyzed on the basis of the classical continuum hydrodynamic theory
      (Stokes-Einstein relationship) and compared with results for the diffusion and
      electrical conductivity of other ionic and nonionic solutes in trehalose and
      sucrose aqueous solutions. Disodium fluorescein obeys the classical model over a
      restricted range of inverse reduced temperatures, T g/ T, scaled by the glass
      transition temperature. Decoupling in neutral solutes takes place at higher
      values of T g/ T, while in ionic solutes it occurs all over the range of T g/ T
      studied, as observed for the water mobility in supercooled sugar solutions.

PMID- 18811197
TI  - Origins of the double asymmetric induction on proline-catalyzed aldol reactions.
AB  - Computational studies to elucidate the origin of the double asymmetric induction
      on proline-catalyzed aldol reaction have been performed using HF/6-31G(d)
      calculations. The computed transition structures explain the experimental data
      obtained.

PMID- 18811198
TI  - Synthesis of enantiomerically pure (S)-methanocarbaribo uracil nucleoside
      derivatives for use as antiviral agents and P2Y receptor ligands.
AB  - We have developed an approach toward enantiomerically pure (S)-methanocarba
      ribonucleosides based on several functional group transformations on a sensitive
      bicyclo[3.1.0]hexane system. D-ribose was transformed into methanocarba alcohol 3
      followed by conversion of the OH group to a nitrile with inversion of
      configuration at C4. The nitrile group was subsequently reduced in two stages to
      the 5'-hydroxymethyl group. An ester group appended to a tertiary carbon (C1) was
      transformed to an amino group as a nucleobase precursor.

PMID- 18811199
TI  - The proton complex of a diaza-macropentacycle: structure, slow formation, and
      chirality induction by ion pairing with the optically active 1,1'-binaphthyl-2,2'
      diyl phosphate anion.
AB  - The protonation of a sterically crowded [N2S6] macropentacycle (1) with 1 equiv
      of CF3SO3H in CDCl3 is slow and gives the singly (oo(+) [1 x H](+)) and doubly
      (o(+)o(+) [1 x 2H](2+)) protonated forms as kinetic products, the i(+)o form of
      [1 x H](+) being the thermodynamic product. i(+)o [1 x H](+) is C3 helically
      chiral in the solid state and in solution. The barrier to racemization
      (DeltaG(double dagger)) of the [1 x H](+) propeller is >71 kJ mol(-1). The
      ammonium proton is encapsulated in the tetrahedral coordination sphere provided
      by the endo (i) nitrogen bridgehead atom and the three proximal thioether
      sulfurs, which makes [1 x H](+) a proton complex. Use of the optically active
      acid (R)-(-)- or (S)-(+)-1,1'-binaphthyl-2,2'-diyl hydrogen phosphate (BNPH) in
      chloroform allowed us to induce a significant diastereomeric excess (24% de),
      which produced a detectable ICD. The de was decreased in acetone-d6 (10%),
      suggesting that the sense of chirality of [1 x H](+) is controlled by ion-pair
      interactions. Detailed NMR studies allowed us to locate the chiral anion on the
      endo side of [1 x H](+), in the cavity lined by endo t-Bu groups, and to
      establish that the rate of anion exchange in [1 x H][(S,R)-(+/-)-BNP] was higher
      than the rate of propeller inversion of [1 x H](+).

PMID- 18811200
TI  - Koshikamide B, a cytotoxic peptide lactone from a marine sponge Theonella sp.
AB  - Koshikamide B (1) has been isolated from two separate collections of the marine
      sponge Theonella sp. as the major cytotoxic constituent. Koshikamide B is a 17
      residue peptide lactone composed of six proteinogenic amino acids, two D-isomers
      of proteinogenic amino acids, seven N-methylated amino acids, and two unusual
      amino acid residues. The unusual amino acids are N(delta)-carbamoylasparagine and
      2-(3-amino-2-hydroxy-5-oxopyrrolidin-2-yl)propionic acid (AHPP); the former is
      first found as the constituent of peptides, whereas the latter is a new amino
      acid residue. The N-terminus of koshikamide B is blocked by a methoxyacetyl
      group. The structure of koshikamide B (1) has been determined by interpretation
      of spectral data and analysis of chemical degradation products. Koshikamide B (1)
      exhibits cytotoxicity against P388 murine leukemia cells and the human colon
      tumor (HCT-116) cell line with an IC50 value of 0.45 and 7.5 microg/mL,
      respectively.

PMID- 18811201
TI  - Synthesis of (+)-didemniserinolipid B: application of a 2-allyl-4-fluorophenyl
      auxiliary for relay ring-closing metathesis.
AB  - The synthesis of didemniserinolipid B utilizing a ketalization/ring-closing
      metathesis (K/RCM) strategy is described. In the course of this work, a novel 2
      allyl-4-fluorophenyl auxiliary for relay ring-closing metathesis (RRCM) was
      developed, which increased the yield of the RCM. The resulting 6,8
      dioxabicyclo[3.2.1]octene core was selectively functionalized by complimentary
      dihydroxylation and epoxidation routes to install the C10 axial alcohol. This
      bicyclic ketal core was further functionalized by etherification and an alkene
      cross metathesis with an unsaturated alpha-phenylselenyl ester en route to
      completing the total synthesis.

PMID- 18811203
TI  - Synthesis of a stable iminium salt and propellane derivatives.
AB  - The treatment of morphinan 1 with NaH and MsCl provided very stable iminium salt
      7 possessing propellane skeleton. One of the synthesized iminium salts 7,
      isobutyl derivative 7b, was crystallized and its structure was determined by X
      ray crystallography. The natural bond orbital analysis suggested that the
      stability of the iminium should result from the stereoelectronic effect
      (hyperconjugation) attributed to their own structures.

PMID- 18811202
TI  - A new efficient route to 2-substituted azulenes based on sulfonyl group directed
      lithiation.
AB  - Directed lithiation of p-tolyl 1-azulenyl sulfone (1) at the 2-position of the
      azulenyl group was achieved by using lithium 2,2,6,6-tetramethylpiperidide
      (LTMP). The azulenyllithium thus generated could be efficiently trapped with
      various electrophiles to form 2-substituted derivatives 2 in moderate to good
      yields. p-Tolyl 2-trimethylsilyl-1-azulenyl sulfone (2a) was transformed into
      cyclic sulfone derivative 3a through the directed lithiation in the p-tolyl group
      and subsequent intramolecular ring closure at the 8-position. 2-(Phenylsulfanyl)
      1-azulenyl p-tolyl sulfone (2b) suffered from desulfonylation to form 2
      phenylsulfanylazulene (4). The Suzuki coupling reaction of 2-iodo-1-azulenyl p
      tolyl sulfone (2d) with arylboronic acids followed by desulfonylation efficiently
      gave 2-arylazulenes 10.

PMID- 18811204
TI  - A synthesis of (-)-mintlactone.
AB  - Mintlactone is synthesized in a concise and efficient way by using a highly
      diastereoselective intramolecular propargylic Barbier reaction, followed by an
      allenol cyclocarbonylation. Tin(II) chloride is found to be the most effective
      reagent for the Barbier reaction.

PMID- 18811205
TI  - Polyoxygenated diterpenes from the sponge Phorbas sp.
AB  - Ten new polyoxygenated diterpenes (7-16) along with six known gagunin compounds
      (1-6) were isolated from the sponge Phorbas sp. collected in the Korean Sea. On
      the basis of a combination of NMR and mass spectroscopic analyses, the molecular
      structures of these diterpenes, designated as gagunins H-Q, were determined to be
      penta- or hexa-oxygenated diterpenes of the 10,13-bis-epi-homoverrucosane class.
      A new diterpene acid (17) of a bisabolane-related skeletal class was also
      isolated and structurally defined by the spectroscopic analyses. These compounds
      exhibited moderate to significant cytotoxicity against the K-562 cell line as
      well as weak inhibitory activity against isocitrate lyase (ICL).

PMID- 18811206
TI  - Alkaloids from the twigs of Daphniphyllum calycinum.
AB  - Twelve new alkaloids, caldaphnidines G-R (1-12), along with 24 known ones, were
      isolated from the twigs of Daphniphyllum calycinum. Their structures were
      elucidated by spectroscopic methods, especially two-dimensional NMR techniques.

PMID- 18811207
TI  - TAC-scaffolded tripeptides as artificial hydrolytic receptors: a combinatorial
      approach toward esterase mimics.
AB  - In this report, we present the first library of tripodal synthetic receptor
      molecules containing three different, temporarily N-terminal protected peptide
      arms capable of performing hydrolytic reactions. To construct this library, the
      orthogonally protected triazacyclophane (TAC)-scaffold was used in the
      preparation of a split-mix library of 19 683 resin bound tripodal receptor
      molecules. For the construction of the peptide arms, three different sets of
      amino acids were used, each focused on one part of the catalytic triad as found
      in several families of hydrolytic enzymes. Therefore, in the sets of amino acids
      used to assemble these tripeptides, basic (containing His and Lys), nucleophilic
      (containing Ser and Cys), or acidic (containing Asp and Glu) amino acid residues
      were present. In addition, nonfunctional hydrophobic amino acid residues were
      introduced. Possible unfavorable electrostatic interactions of charged N-termini
      or their acetylation during screening were circumvented by trifluoroacetylation
      of the N-terminal amines. Screening was performed with a known esterase
      substrate, 7-acetoxycoumarin, which upon hydrolysis gave the fluorescent 7
      hydroxycoumarin, leading to fluorescence of beads containing a hydrolytically
      active synthetic receptor. Although many synthetic receptors contain catalytic
      triad combinations, apparently, only a few showed hydrolytic activity. Sequence
      analysis of the active receptors showed that carboxylate-containing amino acids
      are frequently found in the acidic arm and that substrate cleavage is mediated by
      lysine (noncatalytic) or histidine (catalytic) residues. Kinetic analysis of
      resynthesized receptors showed that catalysis depended on the number of histidine
      residues and was not assisted by significant substrate binding.

PMID- 18811208
TI  - Combinatorial libraries of bis-heterocyclic compounds with skeletal diversity.
AB  - Combinatorial solid-phase synthesis of bis-heterocyclic compounds, characterized
      by the presence of two heterocyclic cores connected by a spacer of variable
      length/structure, provided structurally heterogeneous libraries with skeletal
      diversity. Both heterocyclic rings were assembled on resin in a combinatorial
      fashion.

PMID- 18811209
TI  - Complexation and separation of lanthanides(III) and actinides(III) by
      heterocyclic N-donors in solutions.

PMID- 18811210
TI  - Transients in the formation of nanowire heterostructures.
AB  - We present results on the effect of seed particle reconfiguration on the growth
      of short InAs and InP nanowire segments. The reconfiguration originates in two
      different steady state alloy compositions of the Au/In seed particle during
      growth of InAs and InP. From compositional analysis of the seed particle, the In
      content in the seed particle is determined to be 34 and 44% during InAs and InP
      growth, respectively. When switching between growing InAs and InP, transient
      effects dominate during the time period of seed particle reconfiguration. We
      developed a model that quantitatively explains the effect and with the added
      understanding we are now able to grow short period (<10 nm) nanowire
      superlattices.

PMID- 18811211
TI  - Identifying individual single-walled and double-walled carbon nanotubes by atomic
      force microscopy.
AB  - We show that the number of concentric graphene cylinders forming a carbon
      nanotube can be found by squeezing the tube between an atomic force microscope
      tip and a silicon substrate. The compressed height of a single-walled nanotube
      (double-walled nanotube) is approximately two (four) times the interlayer spacing
      of graphite. Measured compression forces are consistent with the predicted
      bending modulus of graphene and provide a mechanical signature for identifying
      individual single-walled and double-walled nanotubes.

PMID- 18811212
TI  - Heat conductance is strongly anisotropic for pristine silicon nanowires.
AB  - We compute atomistically the heat conductance for ultrathin pristine silicon
      nanowires (SiNWs) with diameters ranging from 1 to 5 nm. The room temperature
      thermal conductance is found to be highly anisotropic: wires oriented along the
      <110> direction have 50-75% larger conductance than wires oriented along the
      <100> and <111> directions. We show that the anisotropies can be qualitatively
      understood and reproduced from the bulk phonon band structure. Ab initio density
      functional theory (DFT) is used to study the thinnest wires, but becomes
      computationally prohibitive for larger diameters, where we instead use the
      Tersoff empirical potential model (TEP). For the smallest wires, the thermal
      conductances obtained from DFT and TEP calculations agree within 10%. The
      presented results could be relevant for future phonon-engineering of nanowire
      devices.

PMID- 18811213
TI  - One-by-one coupling of single defect centers in nanodiamonds to high-Q modes of
      an optical microresonator.
AB  - In this letter, we present the on-demand coupling of single NV(-) defect centers
      in nanodiamonds to a polystyrene microspherical resonator. From an ensemble on a
      coverslip, we select single nanodiamonds containing a single defect proven by a
      pronounced antibunching dip. With the help of a scanning near-field probe, we can
      attach these nanodiamonds to a microsphere resonator one-by-one. A clearly
      modulated fluorescence spectrum demonstrates coupling of the single defect
      centers to high-Q whispering-gallery modes. Our experiments establish a toolbox
      to assemble complex systems consisting of single quantum emitters and (coupled)
      microresonators.

PMID- 18811214
TI  - Synthesis of hybrid multicomponent disklike nanoparticles.
AB  - This manuscript describes the synthesis of a new generation of multicomponent
      disklike nanoparticles. In this work, we present for the first time, through the
      template-based sequential electrochemical deposition of
      metal/semiconductor/polymer segments, an innovative and effective method for
      preparing a wide range of metallic, semiconductor, and polymeric hybrid
      multicomponent disklike nanoparticles covering a wide and controlled dimension
      range from a few nanometers to hundreds of nanometers. Moreover, we can readily
      tailor the desired final size, aspect ratio, and composition of the disklike
      nanoparticles by varying the precursor material used and the electrochemical
      deposition approach. Furthermore, this simple route leads to a highly
      reproducible and high-throughput synthetic platform of new multicomponent and
      multifunctional nanoscale building blocks.

PMID- 18811215
TI  - Effect of electrode roughness on the capacitive behavior of self-assembled
      monolayers.
AB  - Analytical gold electrodes were polished mechanically and electrochemically and
      the true area of the electrode surface was measured by quantitative
      oxidative/reductive cycling of the electrode. A roughness factor for each
      electrode was determined from the ratio of the true area to the geometric area.
      The roughness is fully described by a combination of microscopic roughness (up to
      tens of nanometers) and macroscopic roughness (on the order of hundreds of
      nanometers) terms. The electrodes were then derivatized with a self-assembled
      monolayer (SAM) of dodecanethiol or a thioalkane azacrown and characterized by
      impedance spectroscopy. The behavior of the electrodes was modeled with either a
      Helmholtz or Randles equivalent circuit (depending on the SAM used) in which the
      capacitance was replaced with a constant phase element. From the model, an
      effective capacitance and an alpha factor that quantifies the nonideality of the
      SAM capacitance was obtained. The effective capacitance divided by the roughness
      factor yields the capacitance per unit true area, which is only a function of
      microscopic roughness. The relationship between this capacitance and the alpha
      factor indicates that microscopic roughness predominantly affects the nonideality
      of the film while macroscopic roughness predominantly affects the magnitude of
      the film's capacitance. Understanding the contribution of the electrode
      topography to the magnitude and ideality of the SAM capacitance is important in
      the construction of SAM-based capacitive sensors because it predicts the
      importance of electrode-electrode variations.

PMID- 18811216
TI  - Charge transport in nanoparticle assemblies.

PMID- 18811217
TI  - Novel isocyanide-based three-component one-pot synthesis of cyanophenylamino
      acetamide derivatives.
AB  - A one-pot multicomponent synthesis of a novel class of cyanophenylamino
      acetamides through the conversion of primary amides to the corresponding
      nitriles, starting from simple and readily available inputs including 2
      aminobenzamide, an aldehyde, and an isocyanide in the presence of p
      toluenesulfonic acid as a catalyst, in excellent yields at room temperature in
      ethanol as a green reaction medium is described.

PMID- 18811219
TI  - Blocking of disulfide adsorption by coadsorbing omega-functionalized alkane
      thiols revealed by wet stamping and fluorescence microscopy.
AB  - When alkane thiols and disulfides coadsorb onto gold, they do not necessarily
      create a mixed monolayer. In particular, when thiols are terminated in groups
      capable of hydrogen bonding, they can altogether eliminate adsorption of
      disulfides. Such elimination can be observed directly by using fluorescently
      labeled disulfides and monitoring their adsorption (or lack of) by fluorescence
      microscopy. These experiments suggest a mechanism in which adsorption of thiols
      is facilitated by hydrogen bonding.

PMID- 18811218
TI  - Rapid microwave-assisted CNBr cleavage of bead-bound peptides.

PMID- 18811220
TI  - Mechanism of electrostatic gating at conical glass nanopore electrodes.
AB  - The mechanism of molecule-based electrostatic gating of redox fluxes at conical
      glass nanopore (GNP) electrodes has been investigated using finite-element
      simulations. The results demonstrate that the fluxes of cationic redox molecules
      through the nanopore orifice can be reduced to negligibly small values when the
      surface charge of the nanopore is switched from a negative to a positive value.
      Electrostatic charge reversal can be affected by ionization of surface-bound
      moieties in response to environmental stimuli (e.g., photoionization or acid
      protonation), but only if the negative charge of the glass is included in the
      analysis. Numerical simulations of the responses of GNP electrodes are based on a
      simultaneous solution of the Poisson and Nernst-Planck equations and are in
      excellent agreement with our previously reported experimental results for
      electrostatic gating of the fluxes of Ru(NH 3) 6 (3+) and Fe(bpy) 3 (2+) at GNP
      electrodes with orifice radii between 15 and 100 nm. The gating mechanism is
      discussed in terms of three components: (1) migration of ionic redox species in
      the depletion layer adjacent to the electrode surface; (2) migrational transport
      along the charged pore walls; (3) electrostatic rejection of charged molecules at
      the pore orifice. The numerical results indicate that all three components are
      operative, but that ion migration along the pore walls is dominant.

PMID- 18811221
TI  - Surface plasmon resonances, optical properties, and electrical conductivity
      thermal hystersis of silver nanofibers produced by the electrospinning technique.
AB  - In the present study, silver metal nanofibers have been successfully prepared by
      using the electrospinning technique. Silver nanofibers have been produced by
      electrospinning a sol-gel consisting of poly(vinyl alcohol) and silver nitrate.
      The dried nanofiber mats have been calcined at 850 degrees C in an argon
      atmosphere. The produced nanofibers do have distinct plasmon resonance compared
      with the reported silver nanoparticles. Contrary to the introduced shapes of
      silver nanoparticles, the nanofibers have a blue-shifted plasmon resonance at 330
      nm. Moreover, the optical properties study indicated that the synthesized
      nanofibers have two band gap energies of 0.75 and 2.34 eV. An investigation of
      the electrical conductivity behavior of the obtained nanofibers shows thermal
      hystersis. These privileged physical features greatly widen the applications of
      the prepared nanofibers in various fields.

PMID- 18811222
TI  - Concentrated sodium chloride brine solutions as an additional treatment for
      preventing the introduction of nonindigenous species in the ballast tanks of
      ships declaring no ballast on board.
AB  - Currently, seawater flushing is the only management strategy for reducing the
      number of viable organisms in residual sediments and water of ballast tanks of
      vessels declaring no ballast on board (NOBOB) that traffic ports of the eastern
      United States. Previously, we identified several species of freshwater and
      brackish-water peracarid crustaceans able to survive the osmotic shock that
      occurs during open-ocean ballast water exchange and, potentially, to disperse
      over long distances via ballasted ships and NOBOB vessels. We tested the efficacy
      of concentrated sodium chloride brine solutions as an additional treatment for
      eradicating the halotolerant taxa often present in the ballast tanks of NOBOB
      ships. The lowest brine treatments (30 ppt for 1 h) caused 100% mortality in
      several species of cladocerans and copepods collected from oligohaline habitats.
      Several brackish-water peracarid crustaceans, however, including some that can
      survive in freshwater as well, required higher brine concentrations and longer
      exposure durations (45-60 ppt for 3-24 h). The most resilient animals were widely
      introduced peracarid crustaceans that generally prefer mesohaline habitats but do
      not tolerate freshwater (required brine treatments of 60-110 ppt for 3-24 h).
      Brine treatments (30 ppt) also required less time to cause 100% mortality for
      eight taxa compared with treatments using 34 ppt seawater. Based on these
      experiments and published data, we present treatment strategies for the ballast
      tank biota often associated with NOBOB vessels entering the Great Lakes region.
      We estimate the lethal dosage of brine for 95% of the species in our experiments
      to be 110 ppt (95% confidence interval, 85-192 ppt) when the exposure time is 1 h
      and 60 ppt (95% confidence interval, 48-98 ppt) when the exposure duration is 6 h
      or longer.

PMID- 18811223
TI  - Evaluation of long-term biomarker data from perch (Perca fluviatilis) in the
      Baltic Sea suggests increasing exposure to environmental pollutants.
AB  - Since 1988, biomarkers in female perch (Perca fluviatilis) have been analyzed at
      a reference site on the Swedish Baltic coast. Strong time trends toward
      increasing hepatic ethoxyresorufin-O-deethylase (EROD) activity and reduced
      gonadosomatic index (GSI) have been observed. This could be caused by pollutants
      as well as other factors, such as increasing water temperature or reduced mean
      age of sampled fish. Correlation analyses were used to find the most probable
      explanation for the time trends. The time trends were still significant for EROD
      (p < 0.001) and GSI (p < 0.001) when the correlations were controlled for age.
      Furthermore, increasing water temperature could not explain the time trends.
      Exposure to pollutants through runoff from land was found to be probable, because
      mean flow rate in a nearby river during the last 20 d before sampling correlated
      to EROD activity (p < 0.01). In addition, the sum of EROD activities during the
      life time of the perch (ERODlife) correlated significantly with GSI (p < 0.001).
      This suggests that perch exposed to more EROD-inducing chemicals during their
      lifetime have reduced or delayed gonad development. The time trend in GSI and the
      correlation between ERODlife and GSI were supported by data from a site in the
      Bothnian Bay (northern Baltic Sea; p < 0.05). The results indicate that increased
      rain fall (climate change) can affect the distribution and bioavailability of
      chemicals in coastal areas. The link between EROD and gonad size supports the
      common assumption that biochemical biomarkers can act as early warning signals
      for effects on higher levels, which commonly is difficult to show. The
      significant results can probably be attributed to the unique 20-year data set.

PMID- 18811224
TI  - Nonviable tumor tissue should not upstage Wilms' tumor from stage I to stage II:
      a report from the SIOP 93-01 nephroblastoma trial and study.
AB  - In SIOP trials, Wilms' tumors were labeled as stage II by the presence of
      nonviable and/or viable tumor in the renal sinus and/or perirenal fat. The aim of
      this study was to determine if this approach was justified. Stage II Wilms'
      tumors were reviewed to establish whether staging was due to viable or nonviable
      tumor, and this was related to clinical outcome. One hundred sixty-nine patients
      were included: 40 had stage II due to the presence of nonviable tumor and 129 due
      to viable tumor. Postoperatively, 29 patients were undertreated: 7 with nonviable
      and 22 with viable stage II tumors. No undertreated patient with nonviable stage
      II relapsed or died (event-free survival [EFS] and overall survival [OS] 100%),
      whereas 3 of 22 with viable stage II relapsed, and 2 of them died (EFS 86%, OS
      91%). Of 140 correctly treated patients, only 1 of 33 nonviable stage II patients
      relapsed and died (EFS and OS 97%); 8 of 107 patients with viable stage II
      relapsed (EFS 92%), and 3 of them died (OS 97%). The presence of nonviable tumor
      in the renal sinus and/or perirenal fat does not predict an adverse outcome in
      Wilms' tumors, and alone it does not warrant designation to stage II.

PMID- 18811225
TI  - Direct and indirect effects of a potential aquatic contaminant on grazer-algae
      interactions.
AB  - Contaminants have direct, harmful effects across multiple ecological scales,
      including the individual, the community, and the ecosystem levels. Less, however,
      is known about how indirect effects of contaminants on consumer physiology or
      behavior might alter community interactions or ecosystem processes. We examined
      whether a potential aquatic contaminant, an ionic liquid, can indirectly alter
      benthic algal biomass and primary production through direct effects on
      herbivorous snails. Ionic liquids are nonvolatile organic salts being considered
      as an environmentally friendly potential replacement for volatile organic
      compounds in industry. In two greenhouse experiments, we factorially crossed four
      concentrations of 1-N-butyl-3-methylimidazolium bromide (bmimBr; experiment 1: 0
      or 10 mg/L; experiment 2: 0, 1, or 100 mg/L) with the presence or absence of the
      snail Physa acuta in aquatic mesocosms. Experimental results were weighted by
      their respective control (no bmimBr or P. acuta) and combined for statistical
      analysis. When both bmimBr and snails were present, chlorophyll a abundance and
      algal biovolume were higher than would be expected if both factors acted
      additively. In addition, snail growth rates, relative to those of controls,
      declined by 41 to 101% at 10 and 100 mg/L of bmimBr. Taken together, these two
      results suggest that snails were less efficient grazers in the presence of
      bmimBr, resulting in release of algae from the grazer control. Snails stimulated
      periphyton primary production in the absence, but not in the presence, of bmimBr,
      suggesting that bmimBr also can indirectly alter ecosystem function. These
      findings suggest that sublethal contaminant levels can negatively impact
      communities and ecosystem processes via complex interactions, and they provide
      baseline information regarding the potential effects of an emergent industrial
      chemical on aquatic systems.

PMID- 18811226
TI  - Single- and two-species tests to study effects of the anthelmintics ivermectin
      and morantel and the coccidiostatic monensin on soil invertebrates.
AB  - Soil invertebrates in arable land are potentially exposed to veterinary medicines
      excreted by husbandry. The toxicity of three widely used pharmaceuticals was
      therefore investigated with the use of common soil invertebrates exposed in the
      laboratory in single- or two-species test system. The anthelmintic morantel did
      not cause significant mortality to either Folsomia fimetaria or Enchytraeus
      crypticus even at the highest tested concentration of 900 mg kg(-1) dry soil. The
      coccidiostatic monensin affected the reproduction of F. fimetaria and E.
      crypticus with soil concentrations estimated to cause a 10% effect at values of
      approximately 109 and 71.8 mg kg(-1) dry soil, respectively, but caused no
      mortality to adult. The anthelmintic ivermectin did not affect the survival of
      adult Hypoaspis aculeifer. Reproduction of H. aculeifer declined approximately
      45% in response to ivermectin exposure of 5 mg kg(-1) dry soil. Ivermectin was
      highly toxic to F. fimetaria and affected the survival of adults with soil
      concentrations estimated to cause a 50% mortality at values of 5.3 mg kg(-1) dry
      soil in the single-species test system and 0.14 mg kg(-1) dry soil in the two
      species test system. Reproduction of F. fimetaria was reduced by ivermectin with
      10% effective concentration at 0.19 mg kg(-1) dry soil in the single-species test
      system and 0.02 mg kg(-1) dry soil in two-species test system. It was shown that
      species interactions may influence the response of test organisms to toxic
      substances. The data from this study and previously published data showed that,
      whereas ivermectin is likely to pose a risk to soil-dwelling invertebrates,
      adverse effects of morantel and monensin are unlikely to occur as a result of
      residue excretion from treated farm animals.

PMID- 18811227
TI  - Cellular localization of lead using an antibody-based detection system and enzyme
      activity changes in the gills and digestive gland of the blue mussel Mytilus
      edulis.
AB  - Marine organisms are continuously exposed to heavy metals in their environment.
      Bivalve mollusks such as the blue mussel Mytilus edulis accumulate high levels of
      heavy metals effecting cellular homeostasis and functions. Lead (Pb) exposure
      (2.5 mg/L of lead (II) nitrate for 10 d) and depuration (10 d in clean seawater)
      experiments were conducted to study its intracellular fate in the gills and
      digestive gland of M. edulis. For this purpose, an antibody-based detection
      method for ultrastructural localization and a subcellular fractionation approach
      for chemical analysis of Pb were used. In addition, effects of Pb on enzyme
      activities involved in oxyradical scavenging, such as the conjugative enzyme
      glutathione-S-transferase and the antioxidative enzyme catalase, were determined.
      The ultrastructural studies showed that Pb was mainly detected in lysosomes of
      gill epithelial cells and digestive cells. Lead was also detected in cell nuclei
      and granular hemocytes. Higher metal concentrations were measured by chemical
      analysis in subcellular fractions of the gills compared to those of the digestive
      gland. Increased activities of glutathione-S-transferase were found in gills
      after exposure and remained elevated during the depuration period, whereas
      glutathione-S-transferase activity remained unaffected in the digestive gland.
      Catalase activities showed no changes after Pb exposure, neither in the gills nor
      in the digestive gland. We conclude that gill cells are major sites of uptake and
      accumulation for dissolved Pb and are involved in sequestration and
      detoxification of this metal in M. edulis.

PMID- 18811228
TI  - Perceived educational value and enjoyment of a rural clinical rotation for
      medical students.
AB  - INTRODUCTION: It is well-recognised that medical students whose training exposure
      is largely limited to tertiary-level training hospitals may be inappropriately
      equipped to deal with the most relevant health issues affecting rural
      communities. This article evaluated the perceived educational value of a 2 week
      clinical rotation undertaken by senior undergraduate medical students at rural
      district hospitals and health care centers in the Western Cape Province, South
      Africa. METHODS: Students completed a daily log diary to provide an overview of
      time spent on specific academic activities, ranking the educational and enjoyment
      value of each activity. At the end of the 2 week rotation students completed an
      open-ended questionnaire capturing the main positive and negative aspects of
      their experience, followed by focus group discussions with a randomly selected
      subgroup. In addition, a formal feedback seminar was arranged with the academic
      supervisors at each of the training sites to triangulate the information received
      and to document their perspective. RESULTS: Thirty-seven students consented to
      study participation and 25 (68%) adequately completed the log diaries and
      questionnaires, rating the following activities as most educational: 'assisting
      in theatre', 'teaching by doctor', 'seeing patients in clinic/health centre/OPD'
      and 'mobile clinic excursions'. The rural experience allowed practical
      application of their theoretical knowledge, which improved their levels of
      confidence and enjoyment. The most enjoyed activities were: 'mobile clinic
      excursions', 'performing medical procedures' and 'teaching by doctor'. The
      students were critical of some aspects: (i) the rural rotation was not structured
      efficiently; (ii) compulsory written reports and additional projects prevented
      them from maximizing the rural experience; and (iii) a time period of 2 weeks was
      felt to be too short for optimum benefit from the rotation. CONCLUSION: The
      feedback obtained from this log diary study demonstrates that well-functioning
      rural health care centers provide excellent opportunities for students to develop
      the most relevant practical skills required of generalist doctors working in
      resource-limited settings. In addition to a more efficiently structured rural
      program, students requested an increase in the length of the rotation and a
      reduction in the written academic workload.

PMID- 18811229
TI  - Malaria control in Africa: a mirage a trois.

PMID- 18811230
TI  - Disarming, not destroying: targeting QseC.

PMID- 18811231
TI  - Bacterial protein secretion and trafficking down under. Annual Scientific Meeting
      of the Australian Society for Microbiology, 6-10 July 2008, Melbourne Convention
      Center, Victoria, Australia.

PMID- 18811232
TI  - Recent progress in the management of invasive fungal infections in hematopoietic
      stem cell transplant recipients. 34th Annual Meeting of the European Group for
      Blood and Marrow Transplantation (EBMT), March 30-April 2, 2008, Florence, Italy.

PMID- 18811233
TI  - The phosphate transport system of enteropathogenic Escherichia coli is involved
      in adherence to the host.
AB  - Evaluation of: Ferreira GM, Spira B: The pst operon of enteropathogenic
      Escherichia coli enhances bacterial adherence to epithelial cells. Microbiology
      154(7), 2025-2036 (2008). Enteropathogenic Escherichia coli (EPEC) colonization
      of the human intestinal epithelium constitutes a complex, two-stage process,
      which involves multiple virulence factors that are expressed in response to
      numerous environmental signals. Ferreira and Spira present evidence that the
      phosphate transport system is involved in regulating EPEC colonization in a novel
      manner that does not appear to involve inorganic phosphate sensing.

PMID- 18811234
TI  - Effective host response to Francisella tularensis requires functional mast cells.
AB  - Evaluation of: Ketavarapu JM, Rodriguez AR, Yu J et al.: Mast cells inhibit
      intramacrophage Francisella tularensis replication via contact and secreted
      products including IL-4. Proc. Natl Acad. Sci. USA 105(27), 9313-9318 (2008). The
      intracellular pathogen Francisella tularensis is a highly infectious organism
      that infects cells of the immune system. Mast cells have been known for their
      role in anaphylaxis, although they are also important for their ability to aid in
      the defense against pathogens. The report by Ketavarapu et al. has demonstrated
      that mast cells function to limit the replication of F. tularensis live vaccine
      strain within macrophages in vitro as well as in vivo. It was determined that IL
      4 is one secreted mediator of this effect thus highlights a previously unknown
      mechanism of host defense against F. tularensis.

PMID- 18811235
TI  - HIV epidemiology in Greece.
AB  - Greece has experienced early the effect of HIV/AIDS on morbidity and mortality.
      The era of highly active antiretroviral therapy has alleviated many of the
      consequences of the epidemic, however, HIV infection remains an issue of utmost
      significance. Men who have sex with men are the driving force of the HIV epidemic
      in Greece followed by heterosexually-infected individuals, while infections among
      injecting drug users remain at low levels. HIV-1 molecular epidemiology studies
      reveal a high genetic heterogeneity amongst the circulating strains in Greece.
      The epidemic began with subtype B, as in most of the European countries, however,
      subtype A was detected at a high prevalence among the newly diagnosed HIV-1
      infected individuals in recent years. HIV requires an effective and sustained
      response meeting the needs of vulnerable subpopulations.

PMID- 18811236
TI  - Autophagy, an immunologic magic bullet: Mycobacterium tuberculosis phagosome
      maturation block and how to bypass it.
AB  - Mycobacterium tuberculosis is a facultative intracellular pathogen that
      parasitizes host macrophages where it persists in immature phagosomes by avoiding
      their maturation into phagolysosomes. The mechanisms of how M. tuberculosis
      inhibits phagolysosome biogenesis have been researched in detail and the
      maturation block at least partially depends on the manipulation of host
      phosphoinositide interconversions, with phosphatidylinositol 3-phosphate (PI3P)
      being a central target since it has been shown to be required for phagolysosome
      biogenesis. PI3P earmarks intracellular organelles for binding and assembly of
      effector molecules that interact with PI3P or its derivatives, including Class E
      Vps proteins such as Hrs and ESCRT components, early endosome antigen 1, which
      are required for sequential protein and membrane sorting within the endosomal
      and, by extension, phagosomal systems. In a search of a cellular mechanism that
      can bypass the tubercule bacillus-imposed PI3P block, researchers have uncovered
      a new general bactericidal process, autophagy, which can eliminate intracellular
      pathogens. This is a new, rapidly growing field replete with possibilities for
      novel, previously untried immunologic and pharmacologic interventions applicable
      not only to TB but to other stubborn bacterial, parasitic and viral diseases.

PMID- 18811237
TI  - Resistance issues in treating chronic hepatitis B.
AB  - HBV resistance is the main limitation of long-term therapy with oral HBV
      polymerase inhibitors, which represent the most common approach in the treatment
      of chronic hepatitis B. The complete suppression of HBV replication minimises the
      risk of resistance and therefore close monitoring with sensitive HBV DNA
      determinations at least every 6 months is required. Lamivudine monotherapy has
      the highest risk of selecting resistant mutations compared with other anti-HBV
      agents and is not currently considered as an optimal first-line treatment.
      Adefovir has a similar profile but less potency than the other nucleotide analog,
      tenofovir, whereas telbivudine selects for lamivudine resistance mutants and
      therefore its place is currently unclear. Entecavir and possibly tenofovir are
      the two most potent anti-HBV agents with the best resistance profile in
      nucleo(s)tide-naive patients, while tenofovir represents the optimal treatment
      for patients with lamivudine resistance. Combination of two agents without cross
      resistance should be used in any patient with HBV resistance.

PMID- 18811238
TI  - Thiazolides: a new class of drugs for the treatment of chronic hepatitis B and C.
AB  - Nitazoxanide, the first thiazolide, was originally developed for the treatment of
      Cryptosporidium parvum. The antiviral activity of nitazoxanide was discovered by
      serendipity in patients with AIDS who were treated for cryptosporidial diarrhea
      and had HBV or HCV co-infection. In preliminary open-label studies of patients
      with chronic hepatitis B, nitazoxanide suppressed serum HBV DNA and led to loss
      or seroconversion of hepatitis B e antigen in the majority of patients, as well
      as hepatitis B surface antigen in approximately a quarter of patients. In Phase
      II studies of patients with chronic hepatitis C genotype 4, nitazoxanide combined
      with peginterferon alfa-2a, with or without ribavirin, increased the sustained
      virologic response rate to 79-80 versus 50% with peginterferon plus ribavirin
      standard of care. Randomized, controlled studies of naive and nonresponder
      patients with chronic hepatitis C genotype 1 and patients with chronic hepatitis
      B are underway, and new second generation thiazolides are being developed.

PMID- 18811239
TI  - Acquired vancomycin resistance in clinically relevant pathogens.
AB  - Acquired resistance to vancomycin is an increasing problem in pathogenic
      bacteria. It is best studied and most prevalent among Enterococcus and still
      remains rare in other pathogenic bacteria. Different genotypes of vancomycin
      resistance, vanA-G, have been described. The different van gene clusters consist
      of up to nine genes encoding proteins of different functions; their interplay
      leads to an alternative cell wall precursor less susceptible to glycopeptide
      binding. Variants of vanA and vanB types are found worldwide, with vanA
      predominating; their reservoir is Enterococcus faecium. Within this species a
      subpopulation of hospital-adapted types exists that acquired van gene clusters
      and which is responsible for outbreaks of vancomycin-resistant enterococci all
      over the world. Acquisition of vanA by methicillin-resistant Staphylococcus
      aureus (MRSA) is worrisome and seven cases have been described. Nonsusceptibility
      to glycopeptides also occurs independently from van genes and is a growing
      therapeutic challenge, especially in MRSA.

PMID- 18811240
TI  - Antibiotic-associated diarrhea: epidemiology, trends and treatment.
AB  - A common complication of antibiotic use is the development of gastrointestinal
      disease. This complication ranges from mild diarrhea to pseudomembranous colitis.
      Outbreaks of antibiotic-associated diarrhea (AAD) may also occur in healthcare
      settings, usually caused by Clostridium difficile. AAD typically occurs in 5-35%
      of patients taking antibiotics and varies depending upon the specific type of
      antibiotic, the health of the host and exposure to pathogens. The pathogenesis of
      AAD may be mediated through the disruption of the normal microbiota resulting in
      pathogen overgrowth or metabolic imbalances. The key to addressing AAD is prompt
      diagnosis followed by effective treatment and institution of control measures.
      Areas of active research include the search for other etiologies and more
      effective treatments.

PMID- 18811243
TI  - Cord blood-derived neurons are originated from CD133+/CD34 stem/progenitor cells
      in a cell-to-cell contact dependent manner.
AB  - Previous studies described that neurons could be generated in vitro from human
      umbilical cord blood cells. However, there are few data concerning their origin.
      Notably, cells generating neurons are not well characterized. The present study
      deals with the origin of cord blood cells generating neurons and mechanisms
      allowing the neuronal differentiation. We studied neuronal markers of both total
      fractions of cord blood and stem/progenitor cord blood cells before and after
      selections and cultures. We also compared neuronal commitment of cord blood cells
      to that observed for the neuronal cell line SK-N-BE(2). Before cultures, neuronal
      markers are found within the total fraction of cord blood cells. In CD133+
      stem/progenitor cell fraction only immature neuronal markers are detected.
      However, CD133+ cells are unable to give rise to neurons in cultures, whereas
      this is achieved when total fraction of cord blood cells is used. In fact, mature
      functional neurons can be generated from CD133+ cells only in cell-to-cell close
      contact with either CD133- fraction or a neurogenic epithelium. Furthermore,
      since CD133+ fraction is heterogenous, we used several selections to precisely
      identify the phenotype of cord blood-derived neuronal stem/progenitor cells.
      Results reveal that only CD34- cells from CD133+ fraction possess neuronal
      potential. These data show the phenotype of cord blood neuronal stem/progenitor
      cells and the crucial role of direct cell-to-cell contact to achieve their
      commitment. Identifying the neuron supporting factors may be beneficial to the
      use of cord blood neuronal stem/progenitor cells for regenerative medicine.

PMID- 18811242
TI  - Identification of oxygen-sensitive transcriptional programs in human embryonic
      stem cells.
AB  - To realize the full potential of human embryonic stem cells (hESCs), it is
      important to develop culture conditions that maintain hESCs in a pluripotent,
      undifferentiated state. A low O(2) atmosphere (approximately 4% O(2)), for
      example, prevents spontaneous differentiation and supports self-renewal of hESCs.
      To identify genes whose expression is sensitive to O(2) conditions, microarray
      analysis was performed on RNA from hESCs that had been maintained under either 4%
      or 20% O(2). Of 149 genes differentially expressed, 42 were up-regulated and 107
      down-regulated under 20% O(2). Several of the down-regulated genes are most
      likely under the control of hypoxia-inducing factors and include genes encoding
      enzymes involved in carbohydrate catabolism and cellular redox state. Although
      genes associated with pluripotency, including OCT4, SOX2, and NANOG were
      generally unaffected, some genes controlled by these transcription factors,
      including LEFTY2, showed lowered expression under 20% O(2), while a few genes
      implicated in lineage specification were up-regulated. Although the differences
      between O(2) conditions were generally subtle, they were observed in two
      different hESC lines and at different passage numbers. The data are consistent
      with the hypothesis that 4% O(2) favors the molecular mechanisms required for the
      maintenance of pluripotency.

PMID- 18811244
TI  - A graphical model for evolutionary optimization.
AB  - We present a statistical model of empirical optimization that admits the creation
      of algorithms with explicit and intuitively defined desiderata. Because No Free
      Lunch theorems dictate that no optimization algorithm can be considered more
      efficient than any other when considering all possible functions, the desired
      function class plays a prominent role in the model. In particular, this provides
      a direct way to answer the traditionally difficult question of what algorithm is
      best matched to a particular class of functions. Among the benefits of the model
      are the ability to specify the function class in a straightforward manner, a
      natural way to specify noisy or dynamic functions, and a new source of insight
      into No Free Lunch theorems for optimization.

PMID- 18811245
TI  - The crowding approach to niching in genetic algorithms.
AB  - A wide range of niching techniques have been investigated in evolutionary and
      genetic algorithms. In this article, we focus on niching using crowding
      techniques in the context of what we call local tournament algorithms. In
      addition to deterministic and probabilistic crowding, the family of local
      tournament algorithms includes the Metropolis algorithm, simulated annealing,
      restricted tournament selection, and parallel recombinative simulated annealing.
      We describe an algorithmic and analytical framework which is applicable to a wide
      range of crowding algorithms. As an example of utilizing this framework, we
      present and analyze the probabilistic crowding niching algorithm. Like the
      closely related deterministic crowding approach, probabilistic crowding is fast,
      simple, and requires no parameters beyond those of classical genetic algorithms.
      In probabilistic crowding, subpopulations are maintained reliably, and we show
      that it is possible to analyze and predict how this maintenance takes place. We
      also provide novel results for deterministic crowding, show how different
      crowding replacement rules can be combined in portfolios, and discuss population
      sizing. Our analysis is backed up by experiments that further increase the
      understanding of probabilistic crowding.

PMID- 18811246
TI  - An efficient non-dominated sorting method for evolutionary algorithms.
AB  - We present a new non-dominated sorting algorithm to generate the non-dominated
      fronts in multi-objective optimization with evolutionary algorithms, particularly
      the NSGA-II. The non-dominated sorting algorithm used by NSGA-II has a time
      complexity of O(MN(2)) in generating non-dominated fronts in one generation
      (iteration) for a population size N and M objective functions. Since generating
      non-dominated fronts takes the majority of total computational time (excluding
      the cost of fitness evaluations) of NSGA-II, making this algorithm faster will
      significantly improve the overall efficiency of NSGA-II and other genetic
      algorithms using non-dominated sorting. The new non-dominated sorting algorithm
      proposed in this study reduces the number of redundant comparisons existing in
      the algorithm of NSGA-II by recording the dominance information among solutions
      from their first comparisons. By utilizing a new data structure called the
      dominance tree and the divide-and-conquer mechanism, the new algorithm is faster
      than NSGA-II for different numbers of objective functions. Although the number of
      solution comparisons by the proposed algorithm is close to that of NSGA-II when
      the number of objectives becomes large, the total computational time shows that
      the proposed algorithm still has better efficiency because of the adoption of the
      dominance tree structure and the divide-and-conquer mechanism.

PMID- 18811247
TI  - Genetic algorithms with memory- and elitism-based immigrants in dynamic
      environments.
AB  - In recent years the genetic algorithm community has shown a growing interest in
      studying dynamic optimization problems. Several approaches have been devised. The
      random immigrants and memory schemes are two major ones. The random immigrants
      scheme addresses dynamic environments by maintaining the population diversity
      while the memory scheme aims to adapt genetic algorithms quickly to new
      environments by reusing historical information. This paper investigates a hybrid
      memory and random immigrants scheme, called memory-based immigrants, and a hybrid
      elitism and random immigrants scheme, called elitism-based immigrants, for
      genetic algorithms in dynamic environments. In these schemes, the best individual
      from memory or the elite from the previous generation is retrieved as the base to
      create immigrants into the population by mutation. This way, not only can
      diversity be maintained but it is done more efficiently to adapt genetic
      algorithms to the current environment. Based on a series of systematically
      constructed dynamic problems, experiments are carried out to compare genetic
      algorithms with the memory-based and elitism-based immigrants schemes against
      genetic algorithms with traditional memory and random immigrants schemes and a
      hybrid memory and multi-population scheme. The sensitivity analysis regarding
      some key parameters is also carried out. Experimental results show that the
      memory-based and elitism-based immigrants schemes efficiently improve the
      performance of genetic algorithms in dynamic environments.

PMID- 18811248
TI  - A memetic genetic algorithm for the vertex p-center problem.
AB  - The p-center problem is one of choosing p facilities from a set of candidates to
      satisfy the demands of n clients in order to minimize the maximum cost between a
      client and the facility to which it is assigned. In this article, PBS, a
      population based meta-heuristic for the p-center problem, is described. PBS is a
      genetic algorithm based meta-heuristic that uses phenotype crossover and directed
      mutation operators to generate new starting points for a local search. For larger
      p-center instances, PBS is able to effectively utilize a number of computer
      processors. It is shown empirically that PBS has comparable performance to state
      of-the-art exact and approximate algorithms for a range of p-center benchmark
      instances.

PMID- 18811249
TI  - Role of glucosinolates in insect-plant relationships and multitrophic
      interactions.
AB  - Glucosinolates present classical examples of plant compounds affecting insect
      plant interactions. They are found mainly in the family Brassicaceae, which
      includes several important crops. More than 120 different glucosinolates are
      known. The enzyme myrosinase, which is stored in specialized plant cells,
      converts glucosinolates to the toxic isothiocyanates. Insect herbivores may
      reduce the toxicity of glucosinolates and their products by excretion,
      detoxification, or behavioral adaptations. Glucosinolates also affect higher
      trophic levels, via reduced host or prey quality or because specialist herbivores
      may sequester glucosinolates for their own defense. There is substantial
      quantitative and qualitative variation between plant genotypes, tissues, and
      ontogenetic stages, which poses specific challenges to insect herbivores. Even
      though glucosinolates are constitutive defenses, their levels are influenced by
      abiotic and biotic factors including insect damage. Plant breeders may use
      knowledge on glucosinolates to increase insect resistance in Brassica crops.
      State-of-the-art techniques, such as mutant analysis and metabolomics, are
      necessary to identify the exact role of glucosinolates.

PMID- 18811250
TI  - Detection of direct versus indirect effects: were experiments long enough?
AB  - To evaluate the hypothesis that indirect effects generally take much longer to
      become evident in manipulative studies of community regulation than do direct
      effects and thus may often be missed, I studied the effect of experiment duration
      in a survey of marine intertidal interaction webs. Contrary to expectation,
      indirect effects appeared either simultaneously with direct effects or shortly
      after direct effects were evident. While experiment durations varied greatly, on
      average most direct and indirect effects became statistically significant within
      the first 20%-40% of the total experiment duration. Further, the duration of most
      experiments appeared sufficient so that most indirect effects that would be
      generated by the manipulation could be observed. On average, a period of
      "constancy" (i.e., of no further change) lasting roughly 20%-60% of the total
      experiment duration occurred after the last indirect effect was observed.
      Experiment duration did not vary with web species richness, which suggests no
      tendency to perform manipulations for more (or less) time in more complex webs.
      The number of indirect effects per species did not increase with increasing
      experiment duration, nor did the number of longer interaction chains (four
      species vs. three species), which suggests no trends for increased complexity of
      indirect effects with longer experiments. Ecological theory states that, in
      interaction webs whose dynamics are imperfectly known, indirect effects may
      compromise the predictability of species manipulations. However, empirical
      results suggest that, despite incomplete knowledge of indirect effects, community
      dynamics may be more predictable than expected.

PMID- 18811251
TI  - Three-way interactions among ectomycorrhizal mutualists, scale insects, and
      resistant and susceptible pinyon pines.
AB  - Herbivores and mycorrhizal fungi are important associates of most plants, but
      little is known about how these organisms interact. In a 9-yr experiment, we
      examined how the pinyon needle scale (Matsucoccus acalyptus) affects and is
      affected by the ectomycorrhizal mutualists found on the roots of scale-resistant
      and -susceptible pinyon pines (Pinus edulis). Three major results emerged. First,
      removal experiments demonstrated that scales negatively affected ectomycorrhiza.
      Second, although ectomycorrhiza could either positively or negatively influence
      scale performance by improving plant vigor or increasing plant investment in
      antiherbivore defenses, we found no ectomycorrhizal effect on scale mortality
      when we experimentally enhanced levels of ectomycorrhiza. This represented the
      first test of whether ectomycorrhiza promote plant resistance and contrasted with
      studies showing that arbuscular mycorrhiza negatively affected herbivores. Third,
      pinyon resistance to scales mediated the asymmetrical interaction between fungal
      mutualists and scale herbivores. High scale densities suppressed ectomycorrhizal
      colonization, but only on trees susceptible to scales. Similarities between
      mycorrhiza-herbivore interactions and competitive interactions among herbivores
      suggest broader generalities in the way aboveground herbivores interact with
      belowground plant associates. However, because mycorrhiza are mutualists,
      mycorrhiza-herbivore interactions do not fit within traditional competition
      paradigms. The widespread occurrence and importance of both herbivores and
      mycorrhiza argue for incorporating their interactions into ecological theory.

PMID- 18811252
TI  - An empirically based model for latitudinal gradient in vole population dynamics.
AB  - Vole dynamics in northern Europe exhibit a well-defined geographical gradient,
      with oscillatory populations being confined to high latitudes. It has been
      proposed that oscillations in northern vole populations are driven by their
      interaction with specialist predators (weasels), while the more southern rodent
      populations are relatively stable because of regulation by generalist predators.
      We tested this generalist/specialist predation hypothesis by constructing an
      empirically based model for vole population dynamics, estimating its parameters,
      and making predictions about the quantitative pattern of the latitudinal shift in
      vole dynamics. Our results indicated that the model accurately predicted the
      latitudinal shift in the amplitude and periodicity of population fluctuations.
      Moreover, the model predicted that vole dynamics should shift from stable to
      chaotic as latitude is increased, a result in agreement with nonlinear time
      series analysis of the data. The striking success of the model at predicting the
      shifts in amplitude and stability along the geographical gradient in northern
      Europe provides strong support for the key role of specialist and generalist
      predators in vole population dynamics.

PMID- 18811253
TI  - The relationship among area, elevation, and regional species richness in
      neotropical birds.
AB  - The elevational gradient of species richness is often claimed to mirror the
      latitudinal gradient and has traditionally been explained by assuming a decrease
      in productivity with elevation and more recently by Rapoport's rule. The
      influence of area on the pattern has rarely been considered. Analyses of all
      South American tropical land birds (more than one-fourth of the extant bird
      species on Earth) are used to examine four species richness/elevation models:
      null model, Rapoport's rule, and monotonic or hump-shaped productivity/species
      richness relationships. To quantify the area effect, species-area curves were
      created for seven elevational zones. Not accounting for area, species richness
      declined monotonically with elevation, but area accounted for 67%-91% of the
      variation in species richness per zone. When area was factored out, a hump-shaped
      pattern emerged, with more species in the 500-1,000-m (P<.005) and 1,000-1,500-m
      zones (P<.10) than in the 0-500-m zone. Rapoport's rule and the monotonic
      productivity/species richness relationship were thus not supported. Instead,
      elevational turnover rates and numbers of shared species between zones suggested
      that the hump-shaped pattern reflects geometric constraints (as predicted by the
      null model) imposed by the narrow span of the gradient, and it is suggested that
      midelevational zones may represent sink habitats.

PMID- 18811254
TI  - The role of competition and introduction effort in the success of passeriform
      birds introduced to New Zealand.
AB  - The finding that passeriform birds introduced to the islands of Hawaii and Saint
      Helena were more likely to successfully invade when fewer other introduced
      species were present has been interpreted as strong support for the hypothesis
      that interspecific competition influences invasion success. I tested whether
      invasions were more likely to succeed when fewer species were present using the
      records of passeriform birds introduced to four acclimatization districts in New
      Zealand. I also tested whether introduction effort, measured as the number of
      introductions and the total number of birds released, could predict invasion
      outcomes, a result previously established for all birds introduced to New
      Zealand. I found patterns consistent with both competition and introduction
      effort as explanations for invasion success. However, data supporting the two
      explanations were confounded such that the greater success of invaders arriving
      when fewer other species were present could have been due to a causal
      relationship between invasion success and introduction effort. Hence, without
      data on introduction effort, previous studies may have overestimated the degree
      to which the number of potential competitors could independently explain invasion
      outcomes and may therefore have overstated the importance of competition in
      structuring introduced avian assemblages. Furthermore, I suggest that a second
      pattern in avian invasion success previously attributed to competition, the
      morphological overdispersion of successful invaders, could also arise as an
      artifact of variation in introduction effort.

PMID- 18811255
TI  - Developmental stability and fitness: a review.
AB  - Developmental stability reflects the ability of individuals to undergo stable
      development of their phenotype under a range of environmental conditions.
      Developmental instability is measured in terms of fluctuating asymmetry or
      phenodeviance. A negative relationship between developmental instability and
      fitness has figured as a prominent untested assumption in the literature. A
      review of available information from the literature on the relationship between
      developmental instability and various fitness components such as growth,
      fecundity, and longevity suggests that there indeed is a general negative
      relationship. Symmetrical individuals do generally have faster growth, higher
      fecundity, and better survival than do more asymmetrical individuals. These
      differences appear partially to arise from lower competitive ability and higher
      risks of predation and parasitism of asymmetrical individuals compared with more
      symmetrical conspecifics. The relationship between developmental stability and
      fitness may be either direct or indirect.

PMID- 18811256
TI  - Sperm competition in fishes: the evolution of testis size and ejaculate
      characteristics.
AB  - Fishes show one of the widest ranges of sperm competition intensity of any animal
      group. Here we present a comparative study whose aim is to investigate the effect
      of relative intensity of sperm competition on investment in spermatogenesis and
      the number and size of sperm produced. We find that both the gonadosomatic index
      (GSI = [gonad weight/body weight] x 100) and sperm numbers increase with
      intensity of sperm competition across species but that sperm length decreases.
      These new findings are consistent with a raffle-based mode of sperm competition
      in fishes. Most of these results (positive correlation of the GSI and sperm
      number with sperm competition intensity) concur with the predictions of current
      sperm competition theory. However, we also find that sperm longevity decreases
      with sperm length across species. Current models for continuous fertilization
      suggest that if length increases a sperm's speed but decreases its longevity,
      sperm length should increase with sperm competition intensity, whereas models for
      instant fertilization suggest that sperm length should remain constant. The
      negative relationship found between sperm competition and sperm length therefore
      does not fit predictions of either model.

PMID- 18811257
TI  - Ectoparasitism in mothers causes higher positional fluctuating asymmetry in their
      sons: implications for sexual selection.
AB  - Random deviations from perfect bilateral symmetry, fluctuating asymmetry, arise
      from developmental instability. I tested experimentally whether parasitism in
      female Drosophila nigrospiracula increases fluctuating asymmetry in male
      offspring. I also developed a novel measure for estimating developmental
      instability in a meristic trait called positional fluctuating asymmetry, which is
      based on the difference in the position of thoracic bristles between the right
      and left sternopleuron. I expected this measure to be a more sensitive indicator
      of developmental instability than the traditional numerical fluctuating
      asymmetry, because the latter is based on the difference in the actual presence
      or absence of bristles. Female flies burdened with hematophagous mites,
      Macrocheles subbadius (Macrochelidae), produced sons with significantly higher
      positional fluctuating asymmetry than did females carrying no mites. This effect,
      which may have resulted from impaired provisioning of oocytes by infested
      females, was dose dependent and magnified in the progeny of younger (18-20 d)
      versus older (30-32 d) females. This apparent magnification resulted from a
      slight but not significant increase in asymmetry of offspring of the older and
      unparasitized females. In contrast, the same mite loads had no effect on
      offspring numerical fluctuating asymmetry. If low-positional fluctuating
      asymmetry males enjoy a mating advantage, then with appropriate genetic
      variability, sexual selection could drive the evolution of host resistance in
      host populations. However, variability in neither kind of asymmetry influenced
      male mating success in nature. Thus, although male positional fluctuating
      asymmetry is causally associated with parasitism via maternal effects, asymmetry
      based sexual selection is unlikely to influence the evolution of mite resistance
      in D. nigrospiracula. The value of the sensitivity afforded by positional
      fluctuating asymmetry is discussed in the context of sexual selection and
      conservation biology.

PMID- 18811258
TI  - Behavior of Wolbachia endosymbionts from Drosophila simulans in Drosophila
      serrata, a novel host.
AB  - Many species harbor the incompatibility-inducing microbe Wolbachia, a maternally
      inherited endoparasite that causes reduced egg hatch in crosses between infected
      males and uninfected females. Infected females are immune to this effect, which
      gives them a relative fitness advantage that results in the spread of the
      infection. The strength of incompatibility, fitness deficits associated with the
      infection, and transmission rate from mother to offspring largely determine the
      rate and extent of spread of Wolbachia in a population. We transferred Wolbachia
      from Drosophila simulans to Drosophila serrata, a novel host, and compared
      parameter estimates with those from three naturally occurring Drosophila
      Wolbachia associations believed to be of different ages. Transfected D. serrata
      showed strong incompatibility, low transmission efficiency, and an associated
      fitness deficit, and they would probably be unable to spread in nature. The
      comparisons generally supported the predicted evolution of a host-Wolbachia
      association. The parameters peculiar to any given host-Wolbachia association may
      determine whether the microbial strain can spread in that host.

PMID- 18811259
TI  - Density-dependent parasitoid recruitment per parasitized host: effects on
      parasitoid-host dynamics.
AB  - Models of parasitoid-host dynamics are analyzed that include direct density
      dependence in the host population and either parasitoid- or host-density
      dependent variation in parasitoid recruitment per parasitized host (parasitoid
      "yield"). The principal question addressed is how these forms of density
      dependence in parasitoid dynamics combine with aggregated parasitism to affect
      the stability of the models, in relation to suppression of host abundance. When
      parasitoid yield is an overcompensating function of either parasitoid or host
      density, stability is enhanced for systems with host equilibria suppressed far
      below the host carrying capacity. Substantially less aggregation of parasitism is
      required for stability in this situation than in previous models assuming
      parasitoid yield is constant. However, this density dependence in parasitoid
      yield also reduces stability when the host equilibrium is suppressed only
      moderately below carrying capacity; this is especially true when parasitoid yield
      is more strongly decreased by high host density than is host per capita
      reproduction. At present there is little empirical evidence concerning the
      relationships of parasitoid recruitment to parasitoid and host densities. The
      substantial effects shown in these models suggest that these relationships should
      be considered in empirical studies.

PMID- 18811260
TI  - Does food web complexity eliminate trophic-level dynamics?
AB  - Investigators are always divided into those who are looking for rules and those
      who are looking for exceptions. (Hackett 1937, p. 106).

PMID- 18811261
TI  - Genetic divergence in adaptive characters between sympatric species of
      stickleback.
AB  - This study explored the genetic basis of phenotypic differences between two
      sympatric species of ecologically and morphologically divergent sticklebacks
      (Gasterosteus aculeatus complex). The aim was to understand how many loci
      determine the differences and to what extent the differences are due to additive
      or nonadditive gene action. I reared the two parental species, F1 and F2 hybrids,
      and both backcrosses in the laboratory and measured the following quantitative
      characters: gill raker number and length (both involved in feeding), lateral
      plate number and pelvic spine length (both involved in predator defense), and
      growth (a fitness component). I then applied joint-scaling regression models to
      estimate composite additive, dominance and epistatic effects, and their
      contribution to divergence of parental lines. A simple additive model was
      sufficient for gill raker number and growth; additive and dominance effects
      contributed significantly to divergence in plate number and pelvic spine length;
      and additive, dominance, and epistatic effects contributed significantly to
      divergence in gill raker length. Wright's estimator for the number of loci for
      the four morphological characters ranged from 1 to 50. My results suggest that
      adaptive divergence between limnetic and benthic sticklebacks has taken place
      through a variety of genetic mechanisms specific to different traits. Though
      interspecific hybrids are completely fertile and viable in the laboratory, they
      are selected against in the wild. The pattern of inheritance for the traits
      examined here directly influences how well hybrids can exploit the two major
      resource environments in the wild.

PMID- 18811262
TI  - Population dynamics of a selfish B chromosome neutralized by the standard genome
      in the grasshopper Eyprepocnemis plorans.
AB  - Effects of the B chromosome polymorphism of the grasshopper Eyprepocnemis plorans
      were analyzed in two natural populations. Postmating sexual selection, female
      fertility, and survival were studied. The B chromosome lacks drive and has no
      detectable effects on fitness. A neutral B cannot invade a population and
      establish a polymorphism, but the confidence limits on our estimates cannot
      exclude the possibility that the polymorphism is maintained by a balance between
      weak drive and weak selection against individuals with two and three B's.
      However, other lines of evidence favor the following model of the dynamics of the
      B in E. plorans. In a newly invaded population, the B has substantial drive, but
      the evolution of drive suppressor genes in the A chromosomes neutralizes the B
      drive so that it becomes near-neutral and begins a random walk toward extinction
      by stochastic loss. Because the B is common by the time drive disappears, the
      random walk is likely to continue for a long time. If in the course of the random
      walk a variant B with greater drive appears, then it will displace the original
      variant, and a new cycle of drive suppression and drift to extinction occurs. A
      simulation model of this process suggested that the mean time to extinction is
      proportional to the two-thirds power of the population size; it is much less
      affected by subpopulation size or the number of populations in a subdivided
      population.

PMID- 18811263
TI  - Lekking without a paradox in the buff-breasted sandpiper.
AB  - Females in lek-breeding species appear to copulate with a small subset of the
      available males. Such strong directional selection is predicted to decrease
      additive genetic variance in the preferred male traits, yet females continue to
      mate selectively, thus generating the lek paradox. In a study of buff-breasted
      sandpipers (Tryngites subruficollis), we combine detailed behavioral observations
      with paternity analyses using single-locus minisatellite DNA probes to provide
      the first evidence from a lek-breeding species that the variance in male
      reproductive success is much lower than expected. In 17 and 30 broods sampled in
      two consecutive years, a minimum of 20 and 39 males, respectively, sired
      offspring. This low variance in male reproductive success resulted from effective
      use of alternative reproductive tactics by males, females mating with solitary
      males off leks, and multiple mating by females. Thus, the results of this study
      suggests that sexual selection through female choice is weak in buff-breasted
      sandpipers. The behavior of other lek-breeding birds is sufficiently similar to
      that of buff-breasted sandpipers that paternity studies of those species should
      be conducted to determine whether leks generally are less paradoxical than they
      appear.

PMID- 18811264
TI  - Population consequences of constitutive and inducible plant resistance: herbivore
      spatial spread.
AB  - Little attention has been paid to the impact that constitutive and inducible
      plant resistance traits will have on herbivore spatial dynamics. We investigate
      mathematical models in which herbivore demographic rates and movement rates
      respond to host plant quality, which in turn is determined by constitutive and
      inducible resistance. Models with and without induced resistance yield the same
      analytic expression for the asymptotic speed at which a herbivore population will
      spread through an initially uninduced plant population, suggesting that induced
      resistance will have no effect on the rate of invasion of herbivores that respond
      to plant resistance on small spatial scales. In contrast, constitutive resistance
      will influence the speed of an invasion. If herbivore movement is quite sensitive
      to plant quality, an increase in constitutive resistance can actually accelerate
      the rate of herbivore spread even while it reduces the herbivore's intrinsic rate
      of increase. In other scenarios, the rate of invasion attains a maximum at
      intermediate levels of constitutive resistance. These results argue that our view
      of plant resistance should be broadened to include herbivore movement if we are
      to understand fully the implications of differences in resistance for the
      dynamics of herbivore populations in natural and managed settings.

PMID- 18811265
TI  - Spatial-concentration effects and the importance of local enhancement in the
      evolution of colonial breeding in seabirds.
AB  - The information center hypothesis (ICH) suggests that birds breed in colonies
      because this behavior favors information exchange at the colony about the
      location of food patches. However, the complex suite of behaviors the ICH
      requires implies that information center following is more likely to evolve after
      colonial breeding has become established than to promote its initial development.
      A simpler hypothesis to explain the evolution of colonial breeding is that
      coloniality concentrates foragers in space, which leads to more rapid discovery
      of food patches and, by means of local enhancement, more efficient transfer of
      information about the location of patches than if foragers bred in a dispersed
      fashion. To assess the effects of breeding dispersion on foraging success, I
      simulated the foraging behavior of cliff-breeding seabirds (nesting either
      solitarily or colonially) searching for patchily distributed prey. Results show
      that colonial breeding is favored when food patches are sufficiently large or
      short-lived that competition for food is ameliorated. Conversely, dispersed
      nesting is favored when patches are small or long-lived. Individuals playing a
      colonial breeding strategy can invade a population of solitarily breeding birds,
      and once a colonial breeding strategy becomes established, it generally is
      resistant to invasion. These findings suggest that the spatial-concentration
      model is a plausible mechanism for the initial development of coloniality.

PMID- 18811266
TI  - Exploratory path analysis with applications in ecology and evolution.
AB  - In this article, I first describe some recent developments in the identification
      of the structure of dependencies among variables in multivariate data relevant to
      exploratory path analysis. I then introduce a bootstrap modification of one
      important method (the SGS algorithm) that is designed to improve error rates of
      exploratory path analysis in the small data sets that are typical of studies in
      ecology and evolution. Monte Carlo results indicate that this modified technique
      can find path models that are close to the true model even in very small data
      sets. The bootstrapped SGS algorithm is then applied to a previously published
      data set involving attributes affecting seed dispersal in St. Lucie's cherry.

PMID- 18811267
TI  - A phylogenetic reconstruction of constitutive and induced resistance in
      Gossypium.

PMID- 18811268
TI  - Evidence for an evolutionary history of overcompensation in the grassland
      biennial Gentianella campestris (Gentianaceae).

PMID- 18811269
TI  - How often does sympatry affect sexual isolation in Drosophila?

PMID- 18811270
TI  - Clutch size and cavity excavation in parids (Paridae): the limited breeding
      opportunities hypothesis tested.

PMID- 18811273
TI  - Evolution of a species' range.
AB  - Gene flow from the center of a species' range can stymie adaptation at the
      periphery and prevent the range from expanding outward. We study this process
      using simple models that track both demography and the evolution of a
      quantitative trait in a population that is continuously distributed in space.
      Stabilizing selection acts on the trait and favors an optimum phenotype that
      changes linearly across the habitat. One of three outcomes is possible: the
      species will become extinct, expand to fill all of the available habitat, or be
      confined to a limited range in which it is sufficiently adapted to allow
      population growth. When the environment changes rapidly in space, increased
      migration inhibits local adaptation and so decreases the species' total
      population size. Gene flow can cause enough maladaptation that the peripheral
      half of a species' range acts as a demographic sink. The trait's genetic variance
      has little effect on species persistence or the size of the range when gene flow
      is sufficiently strong to keep population densities far below the carrying
      capacity throughout the range, but it can increase the range width and population
      size of an abundant species. Under some conditions, a small parameter change can
      dramatically shift the balance between gene flow and local adaptation, allowing a
      species with a limited range to suddenly expand to fill all the available
      habitat.

PMID- 18811274
TI  - Comparisons of physiological performance in sexual and asexual whiptail lizards
      (genus Cnemidophorus): implications for the role of heterozygosity.
AB  - Many asexual animal species are of hybrid origin, with consequent high levels of
      heterozygosity. Data from some studies suggest that increased heterozygosity may
      be functionally correlated with superior performance in a variety of fitness
      related traits. Thus, hybrid asexual species could be expected to exhibit some
      degree of heterosis. This spontaneous heterosis hypothesis is tested in a
      comparative study of asexual and sexual species of the lizard genus
      Cnemidophorus. Asexual species of the genus are parthenogenetically reproducing
      hybrids of the sexual species and as a result have high levels of heterozygosity
      that have persisted since their origins. Five whole-organism physiological traits
      (burst speed, endurance, maximal exertion, standard metabolic rate, and
      evaporative water loss rate) were examined in five asexual species and the sexual
      species that gave rise to them. Trait values for sexual and asexual species were
      compared using a nonphylogenetic approach and two phylogenetically controlled
      approaches capable of dealing with reticulate phylogenies. In contrast to the
      predictions of the heterosis hypothesis, performance for four of the traits in
      asexual Cnemidophorus was not statistically different than that in their sexual
      parental species, and asexuals had significantly worse endurance. On the whole,
      the overall trend appeared to be toward worse performance in asexuals. An obvious
      interpretation of these results is that heterozygosity and "vigor" need not be
      functionally related. However, other factors may be counterbalancing possible
      beneficial effects of heterozygosity, including detrimental epistatic effects
      resulting from the karyotypically mixed genome of these hybrids, and the
      accumulation of deleterious mutations in the asexual lineages via Muller's
      ratchet.

PMID- 18811275
TI  - Reproductive strategies of marine benthic invertebrates revisited: facultative
      feeding by planktotrophic larvae.
AB  - Fecundity-time models of reproductive strategies in marine invertebrates all
      predict that reproductive success is maximized only at the extreme levels of
      investment. Selection should drive egg sizes toward small eggs and planktotrophy
      or large eggs and lecithotrophy. The existence of two distinct larval types,
      feeding and nonfeeding, has been taken as confirmation of this prediction and has
      established the current paradigm for larval ecology. However, comparative and
      experimental evidence does not support the prediction that egg size is minimized
      in species with planktotrophic larvae. Recent discoveries have documented the
      existence of planktotrophs that have intermediate egg sizes, differing degrees of
      dependence on exogenous food, and differing capacities for facultative feeding. A
      fecundity-time model is presented that includes facultative larval feeding by
      dissociating the onset of feeding capability from the need for exogenous food.
      The facultative feeding model shows that reproductive success can be maximized at
      intermediate levels of investment per offspring between the minimum for
      development and the threshold for lecithotrophy, depending on the amount of food
      available to larvae and the intensity of planktonic mortality. A continuum of
      larval strategies is predicted.

PMID- 18811276
TI  - Sequential patterns of sex allocation in simultaneous hermaphrodites: do we need
      models that specifically incorporate this complexity?
AB  - Theoretical and empirical studies of sex allocation usually treat sequential and
      simultaneous hermaphroditism as distinct and disparate forms of allocation.
      However, the sexual patterns of numerous species have both sequential (e.g., size
      based) and simultaneous components. In most cases, we have drawn from sex
      allocation theory developed for sequential hermaphrodites to explain ontogenetic
      changes in allocation and from theory developed for simultaneous hermaphrodites
      to explain the remaining aspects of these sexual patterns rather than develop a
      more integrated theory. Here I present the evolutionary stable solution (ESS) to
      a dynamic statevariable model that explicitly combines the effects of size and
      simultaneous allocation to male and female function in a dynamic game. The model
      structure and initial parameter values are based on the sexual pattern of the
      blue-banded goby, Lythrypnus dalli, a simultaneous hermaphrodite. I then compare
      the natural patterns of sex allocation in L. dalli with the predictions of the
      model and with those of a dynamic version of the size advantage model. The
      integrated model predicted variation in allocation, sex-specific size
      distributions, and seasonal sex ratio better than the sequential hermaphroditism
      model did. Indeed, the sequential model, using L. dalli parameter values,
      predicts a dioecious rather than sequentially hermaphroditic allocation pattern.
      The comparison of these two models illustrates the disadvantage of drawing from
      two bodies of theory without a formal integrated framework. Furthermore, the
      comparison focuses attention on the role of costs of reallocation in the
      evolution of mixed (or intermediate) sexual patterns.

PMID- 18811277
TI  - Female mate choice tactics in a resource-based mating system: field tests of
      alternative models.
AB  - In this study we test theoretical models of female mate choice tactics in natural
      populations of pine engravers, Ips pini (Say) (Coleoptera: Scolytidae), a species
      with a resource-based mating system and high search costs. We first develop
      distinguishing predictions for each of four models of mate choice: random,
      comparison tactics, and fixed and adjustable thresholds. These predictions relate
      to commonly collected field data that include the visiting behavior of females
      and the quality of accepted and rejected mates. Using these types of data, we
      conclude that pine engravers use an adjustable threshold mate choice tactic
      because females often accepted the first male encountered, rarely revisited
      males, visited similar numbers of males in patches of different quality, accepted
      higher-quality males than those they rejected even on their first encounter with
      a male in a patch, and had higher acceptance thresholds in high-quality patches
      than in low-quality patches. This adjustable threshold tactic is consistent with
      a one-step decision rule and is predicted to occur in species such as pine
      engravers in which search costs are high and females have information about patch
      quality before beginning a search in a patch.

PMID- 18811278
TI  - Physiology, allocation, and growth rate: a reexamination of the tilman model.

PMID- 18811279
TI  - Rapoport's rule: a comparative analysis between South and North American columnar
      cacti.

PMID- 18811280
TI  - Life on the edge: adaptation versus environmentally mediated gene flow in the
      snow buttercup, Ranunculus adoneus.
AB  - We used experimental transplant studies to understand how dispersal and habitat
      specific selection interact to influence plant populations occupying
      heterogeneous environments. The snow buttercup (Ranunculus adoneus) occupies a
      steep ecological and flowering time gradient caused by persistent snowmelt
      differences within its snow bed habitat. We transplanted seeds, seedlings, and
      adults to learn about the potential interactions between dispersal and selection.
      We found that adaptive differentiation is not occurring along the snowmelt
      gradient, despite striking differences in microhabitat conditions and
      reproductive phenology between early- and latemelting sites. Instead, our results
      imply that environmentally based differences in seed quality are contributing to
      directional gene flow from early-melting locations toward latemelting locations.
      Emergence and early survival of seedlings is greater in late-melting sites in
      some years, but the larger seeds produced by maternal plants in early-melting
      locations consistently have a fitness advantage in all parts of the snow bed.
      Larger seeds survive longer in the soil and have a second peak of seedling
      emergence in their third year, but these late-emerging seedlings are successful
      only if dispersed to less vegetated, late-melting destinations. The longer
      growing season in earlymelting sites enhances vegetative growth at all life
      history stages and increases fecundity of seedling transplants but also limits
      the opportunity for establishment from seed. Our demographic analysis suggests
      that maternal environmental effects on propagule quality can lead to directional
      gene flow from benign to marginal sites in populations occupying heterogeneous
      habitats.

PMID- 18811281
TI  - Does sociality drive the evolution of communicative complexity? A comparative
      test with ground-dwelling sciurid alarm calls.
AB  - While sociality has been hypothesized to drive the evolution of communicative
      complexity, the relationship remains to be formally tested. We derive a
      continuous measure of social complexity from demographic data and use this
      variable to explain variation in alarm repertoire size in ground-dwelling sciurid
      rodents (marmots, Marmota spp.; prairie dogs, Cynomys spp.; and ground squirrels,
      Spermophilus spp.). About 40% of the variation in alarm call repertoire size was
      explained by social complexity in the raw data set. To determine the degree to
      which this relationship may have been influenced by historical relationships
      between species, we used five different phylogenetic hypotheses to calculate
      phylogenetically independent contrasts. Less variation was significantly
      explained in contrast-based analyses, but a general positive relationship
      remained. Social complexity explained more variation in alarm call repertoire
      size in marmots, while sociality explained no variation in repertoire size in
      prairie dogs and no variation in phylogenetically based analyses of squirrels. In
      most cases, substantial variation remained unexplained by social complexity. We
      acknowledge that factors other than social complexity, per se, may contribute to
      the evolution of alarm call repertoire size in sciurid rodents, and we discuss
      alternative hypotheses. Our measure of social complexity could be used by other
      researchers to test explicit evolutionary hypotheses that involve social
      complexity.

PMID- 18811282
TI  - The relation among gonadal steroids, immunocompetence, body mass, and behavior in
      young black-headed gulls (Larus ridibundus).
AB  - We experimentally examined the effect of testosterone on the antibody response to
      a single immunization with sheep red blood cells in young black-headed gulls.
      This species performs a number of testosterone-mediated elaborate postural
      displays in social interactions and breeds in dense colonies in which there is a
      high likelihood of infectious diseases. In young chicks, only one-third were
      capable of responding to immunization. In the responding chicks, testosterone
      enhanced antibody titers. Even when antibody responsiveness was measured >1 mo
      after the termination of hormonal treatment, antibody responses were enhanced in
      birds treated with androgen but not estrogen. At 9 mo of age, all birds responded
      to immunization, but there was no effect of testosterone on antibody titers. In
      these juveniles, frequency of display behavior was negatively related to changes
      in body mass, which suggests that displaying is energetically costly. Despite
      decreased body mass, antibody titers were highest in birds that displayed more
      frequently. This suggests that displaying signals immunocompetence. The results
      are discussed in relation to the immunocompetence handicap hypothesis and to what
      is known of the influence of the bursa of Fabricius and social stress on antibody
      production.

PMID- 18811283
TI  - Evolution of reproductive effort in a metapopulation with local extinctions and
      ecological succession.
AB  - Using a metapopulation model, we study how local extinctions, limited population
      life span, and local demographic disequilibrium affect the evolution of the
      reproductive effort in a species with overlapping generations but no senescence.
      We show that in a metapopulation with saturation of all sites and an infinite
      deme maximal life span (no succession), local extinctions simply constitute an
      additional source of extrinsic mortality. When either the hypothesis of an
      infinite deme maximal life span or the saturation hypothesis is relaxed,
      nontrivial predictions arise. in particular, we find interactions between the
      evolutionarily stable reproductive effort strategy and the demographic dynamics
      in the metapopulation. We predict that larger reproductive effort may be selected
      for in habitats of poorer productivity, contrary to what would be predicted in a
      single population. Also, we predict that higher dispersal rates should favor
      selection for lower reproductive efforts. However, metapopulation parameters that
      favor high dispersal rates also favor larger reproductive efforts. Conflicting
      selection pressures in the metapopulation also allow maintaining evolutionarily
      stable polymorphism between a low and high reproductive effort for particular
      trade-offs between survival and fecundity.

PMID- 18811284
TI  - Life-history consequences of egg size in Drosophila melanogaster.
AB  - We used a novel approach to study the effects of egg size on offspring fitness
      components in Drosophila melanogaster. Populations that differed genetically in
      egg size were crossed, and the female offspring from these reciprocal crosses
      were examined for life-history traits. These flies expressed effects of egg size,
      because they developed from eggs of different sizes as a result of maternal
      genetic effects, but displayed an equivalent range of nuclear genetic variation.
      The crosses used four independent pairs of outbred populations that differed in
      the pattern of covariation between egg size and life-history traits, so that the
      maternal genetic effects of egg size on offspring characters could be contrasted
      to the associations present among the parental populations. Egg size showed
      positive maternal genetic effects on embryonic viability and development rate,
      hatchling weight and feeding rate, and egg-larva and egg-adult development rate
      but no consistent effects on larval competitive ability, adult weight, or egg
      size in the offspring. Our method revealed a pattern of causality that could not
      be deduced from interpopulation comparisons and therefore provides a good way of
      disentangling the causes and consequences of variation in egg size while
      controlling for zygotic genetic effects.

PMID- 18811285
TI  - Balanced dispersal between spatially varying local populations: an alternative to
      the source-sink model.
AB  - Analysis of long-term monitoring data on breeding collared flycatchers (Ficedula
      albicollis Temm.) has revealed equal numbers of immigrations and emigrations
      between neighboring populations of different sizes. Dispersal patterns were close
      to patterns simulated under a conditional dispersal and with populations near
      saturation level. Local growth rates of the 11 sites were computed and did not
      support the idea that the observed balanced exchanges could be the result of a
      source-sink system. This is the first empirical evidence for a system of discrete
      habitat patches with component populations that exist as simultaneous sources and
      sinks to their neighbors. Dispersal propensities were inversely related to
      population sizes, which showed little variation in time. These results are
      consistent with recent modeling of dispersal as an evolutionarily stable
      strategy, and they demonstrate that dispersal can be an active phenomenon
      requiring neither the dominance hierarchies nor the temporal instability
      generally invoked by ecological and population genetic models. We note a parallel
      to the concept of Ideal Free Distributions and discuss implications for the
      evolution of dispersal mechanisms in fragmented populations.

PMID- 18811286
TI  - Evolution of prolonged development: a life table analysis for periodical cicadas.
AB  - According to conventional wisdom, natural selection should favor early
      reproduction. Prolonged development of 13 and 17 yr has been difficult to explain
      for periodical cicadas. Earlier, I hypothesized that development may be long for
      periodical cicadas because fecundity increases as a function of longer
      development with little increased risk of mortality. In this article, I tested
      whether the fecundity was greater for 17-yr cicadas than for 13-yr cicadas and
      estimated the shape of the survivorship curve. A cohort of 17-yr cicadas was
      followed from 1979 through 1996. Most mortality occurred during the first 2 yr;
      thereafter mortality was uncommon. Across 17 yr, adult densities increased at
      five out of seven sites, and in no case did the change exceed three times.
      Seventeen-year adults had heavier ovaries than did 13-yr adults; this effect was
      greater for Magicicada cassini (1.80 times) than for Magicicada decim (1.16
      times). For M. cassini, the extra fecundity associated with 17-yr development
      swamped the potential advantages of more frequent reproduction of 13-yr forms
      under most conditions. For M. decim, realistically low rates of mortality roughly
      matched the small effect of development on fecundity. Prolonged development in
      periodical cicadas may be explained adequately by the demographic hypothesis,
      although it may also reduce predation risk to adults or result from strong
      selection for large body size.

PMID- 18811287
TI  - When can a clonal organism escape senescence?
AB  - Some clonal organisms may live for thousands of years and show no signs of
      senescence, while others consistently die after finite life spans. Using two
      models, we examined how stage-specific life-history rates of a clone's modules
      determine whether a genetic individual escapes senescence by replacing old
      modules with new ones. When the rates of clonal or sexual reproduction and
      survival of individual modules decline with age, clones are more likely to
      experience senescence. In addition, the models predict that there is a greater
      tendency to find senescence in terms of a decline in the rate of sexual
      reproduction with clone age than in terms of an increase in the probability of
      clone mortality, unless rates of sexual reproduction increase dramatically with
      module stage. Using a matrix model modified to represent the clonal lifestyle, we
      show how a trade-off between sexual and clonal reproduction could result in
      selection for or against clonal senescence. We also show that, in contrast to
      unitary organisms, the strength of selection on life-history traits can increase
      with the age of a clone even in a growing population, countering the evolution of
      senescence.

PMID- 18811288
TI  - Cost of chemically defending seeds: furanocoumarins and Pastinaca sativa.

PMID- 18811289
TI  - Distribution, diversity, and latitude in African primates.

PMID- 18811290
TI  - Wolf pack size and food acquisition.

PMID- 18811291
TI  - Vegetation effects on soil resource heterogeneity in prairie and forest.
AB  - A current, widespread example of vegetation change is the invasion of grassland
      by woody plants. This is associated with an increase in soil heterogeneity, and
      it has been argued that woody plants both cause and benefit from high
      heterogeneity. We know of no experimental demonstrations of differences between
      grasses and woody plants in their effects on heterogeneity. Here we compare
      heterogeneity between mixed-grass prairie and aspen forest, and we report the
      results of a soil transplant experiment that tested for differences between these
      vegetation types in their effects on soil resource heterogeneity. We measured the
      heterogeneity of resources and plant mass along 10 transects in both prairie and
      aspen forest in spring and summer. Light and available nitrogen (N; sum of
      ammonium and nitrate) were significantly more variable in forest than prairie, as
      were root and understory shoot mass. The variability of soil moisture and
      topography did not differ between prairie and forest. In our experiment, N and
      water in cores of prairie soil moved to forest attained the relatively high
      variability of forest soils. Further, forest soils moved to prairie attained the
      relatively low variability of prairie soils. In summary, both the biomass
      heterogeneity measurements and the soil transplant experiment suggested that
      plant uptake contributed to greater heterogeneity in forests.

PMID- 18811292
TI  - Disentangling effects of induced plant defenses and food quantity on herbivores
      by fitting nonlinear models.
AB  - Plants can respond to herbivore damage through both broad-scale (systemic) and
      localized induced responses. While many studies have quantified the impact of
      systemic responses on herbivores, measuring the impact of localized changes is
      difficult because plant tissues that have suffered direct damage may represent
      both a lower quality and a lower quantity of food. This article uses nonlinear
      models to disentangle the confounding effects of prior herbivory on food quantity
      and quality. The first (null) model assumes that herbivore performance is
      determined only by the quantity of food available to an average herbivore.
      Modified models allow two distinct effects of damage-induced defenses: an
      increase in the amount of food each herbivore is required to consume in order to
      achieve maximum performance and a reduction in the maximum performance even when
      herbivores are fed ad lib. Maximum likelihood methods were used to fit the models
      to data from field experiments in which Colorado potato beetle (Leptinotarsa
      decemlineata) larvae were reared on three varieties of potatoes that had been
      damaged to varying degrees by adult beetles. Prior damage reduced the mean mass
      of beetles at pupation, and this effect was due to both a decrease in food
      quantity and induced changes in food quality. In contrast, beetle survival was
      affected in some cases by reduced food quantity but showed no responses that
      could be attributed to induced defenses. I discuss this result in the context of
      previous studies of induced (mostly systemic) responses in the potato-potato
      beetle system, and I suggest that detailed studies of particular chemical
      responses and the proposed method of combining bioassays with quantitative models
      should be used as complementary approaches in future studies of herbivore-induced
      defenses in plants.

PMID- 18811293
TI  - Yield and dynamics of tritrophic food chains.
AB  - Strong relationships between yield and dynamic behavior of tritrophic food chains
      are pointed out by analyzing the classical Rosenzweig-MacArthur model. On the one
      hand, food chains are subdivided into undersupplied and oversupplied categories,
      the first being those in which a marginal increase of nutrient supply to the
      bottom produces a marginal increase of mean yield at the top. On the other hand,
      a detailed bifurcation analysis proves that dynamic complexity first increases
      with nutrient supply (from stationary to a low-frequency cyclic regime and,
      finally, to chaos) and then decreases (from chaos to a high-frequency cyclic
      regime). A careful comparison of the two analyses supports the conclusion that
      food chains cycling at high frequency are oversupplied, while all others are
      undersupplied. A straightforward consequence of this result is that maximization
      of food yield requires a chaotic regime. This regime turns out to be very often
      on the edge of a potential catastrophic collapse of the top component of the food
      chain. In other words, optimality implies very complex and dangerous dynamics, as
      intuitively understood long ago for ditrophic food chains by Rosenzweig in his
      famous article on the paradox of enrichment.

PMID- 18811294
TI  - Secondary metabolites of fleshy vertebrate-dispersed fruits: adaptive hypotheses
      and implications for seed dispersal.
AB  - We discuss seven hypotheses to explain the adaptive significance of secondary
      metabolites in ripe fleshy fruits and their implications for seed dispersal.
      These hypotheses are the attraction/association, seed germination inhibition,
      attraction/repulsion, protein assimilation, gut retention time, directed
      toxicity, and defense trade-off hypotheses. We examine evidence that supports or
      refutes these hypotheses and suggest further tests of each. In addition, we
      summarize recent work with Solanum fruit pulp glycoalkaloids that bears directly
      on three of these hypotheses (directed toxicity, gut retention time, and defense
      trade-off). We conclude that evidence addressing many of these hypotheses is
      either observational or indirect, but most hypotheses find at least some level of
      support. Because many of the hypotheses are not mutually exclusive, we also
      conclude that synergistic interactions and multifunctionality in secondary
      metabolites may provide economical evolutionary solutions for plants facing
      disparate and temporally variable selective pressures that impinge on fruits and
      seeds.

PMID- 18811295
TI  - Mutualism among safe, selfish sentinels: a dynamic game.
AB  - Sentinels are group members that watch from prominent positions. Sentinel
      interchanges often appear orderly, and groups with sentinels rarely have zero or
      many sentinels. A dynamic game was constructed to examine if these observations
      about sentinels could be based on selfish actions by individual group members. In
      this game, each group member chose to forage or be a sentinel based on its own
      energetic state and the actions of others. Sentinels received a selfish
      antipredator benefit if their ability to detect approaching predators more than
      compensated for their increased exposure to undetected predators. Provided
      sentinels were relatively safe and that detection information spread to other
      group members when sentinels detected predators, sentinels appeared highly
      coordinated for all combinations of parameters. This apparent coordination was
      based on mutualism because each individual gained by being a sentinel when other
      group members were not (and foraging when other group members were being
      sentinels). The model was very robust, but exact level of sentinel behavior
      varied somewhat with changes in foraging and predation parameters. This model
      could best be tested by testing its assumptions about sentinel safety, foraging
      predation trade-offs, and information transfer in groups.

PMID- 18811296
TI  - Functions of fights in territory establishment.
AB  - Fights are often observed when prospective territory owners settle in patches of
      vacant habitat, but the function of these fights in space acquisition is obscure.
      This study tests two hypotheses about the effect of fights on subsequent space
      use patterns: first, that settlers win space by winning fights and, second, that
      fights encourage the establishment of mutually exclusive home ranges between
      opponents (i.e., "fights make neighbors"). The behavior of juvenile Anolts aeneus
      lizards was recorded as they established territories in patches of habitat in the
      field. In support of the fights-make-neighbors hypothesis, opponents whose last
      aggressive interaction was a fight were six times more likely to have mutually
      exclusive home ranges at the end of the settlement period than were otherwise
      equivalent dyads whose last encounter was a chase. Contra the hypothesis that
      settlers win space by winning fights, most last fights ended in a draw, and there
      was no discernable relationship between the outcome of last fights and the
      subsequent space use of the contestants. These and previous analyses of
      settlement behavior in this species suggest that fights during the settlement
      period encourage the formation of symmetrical social and spatial relationships
      between neighboring settlers.

PMID- 18811297
TI  - Local population structure and sex ratio: evolution in gynodioecious plants.
AB  - Although the influence of population structure on evolution has been explored
      previously in a variety of theoretical studies, there are few examples of
      specific traits whose fitness is likely to be modified by the local structure.
      Here we focus on a specific trait, sex expression in gynodioecious plants, and
      derive a model in which the fitness of females and hermaphrodites is a function
      of the local sex ratio. By using the concept d genes. As a consequence, when
      local demes vary in sex ratio, a polymorphism for a cytoplasmic male sterility
      (CMS) allele can be maintained in the absence of nuclear alleles that restore
      male function. When of subjective frequencies, it is shown that among-deme
      variance in the local sex ratio reduces the average fitness of females when
      pollen availability limits fertility. In contrast, sex ratio variance increases
      the fitness of hermaphrodites from the perspective of maternally inherited genes
      and lessens the negative impact of pollen limitation on hermaphrodite fitness
      when it is measured from the perspective of biparentally inheriterestorer alleles
      are introduced into the model, polymorphism cannot be maintained simultaneously
      at both the cytoplasmic and nuclear loci. In that case, the CMS allele spreads to
      fixation, and the equilibrium frequency of females is an inverse function of the
      equilibrium frequency of the restorer allele, which increases with increased
      structure. The results exemplify how population structure can greatly alter the
      fitness and evolution of a frequency-dependent trait.

PMID- 18811298
TI  - Opossum sex ratios revisited: significant or nonsignificant?

PMID- 18811299
TI  - The roles of harsh and fluctuating conditions in the dynamics of ecological
      communities.
AB  - Harsh conditions (e.g., mortality and stress) reduce population growth rates
      directly; secondarily, they may reduce the intensity of interactions between
      organisms. Near-exclusive focus on the secondary effect of these forms of
      harshness has led ecologists to believe that they reduce the importance of
      ecological interactions, such as competition, and favor coexistence of even
      ecologically very similar species. By examining both the costs and the benefits,
      we show that harshness alone does not lessen the importance of species
      interactions or limit their role in community structure. Species coexistence
      requires niche differences, and harshness does not in itself make coexistence
      more likely. Fluctuations in environmental conditions (e.g., disturbance,
      seasonal change, and weather variation) also have been regarded as decreasing
      species interactions and favoring coexistence, but we argue that coexistence can
      only be favored when fluctuations create spatial or temporal niche opportunities.
      We argue that important diversity-promoting roles for harsh and fluctuating
      conditions depend on deviations from the assumptions of additive effects and
      linear dependencies most commonly found in ecological models. Such considerations
      imply strong roles for species interactions in the diversity of a community.

PMID- 18811300
TI  - Omnivory as a stabilizing feature of natural communities.
AB  - Omnivory-defined broadly as feeding on more than one trophic level-occupies a
      prominent position in discussions of food web architecture and dynamics, due in
      large part to an enduring conflict regarding omnivory's role in community
      dynamics. According to classical results from mathematical food web theory,
      omnivory destabilizes ecological communities, whereas more recent conceptual
      syntheses suggest that omnivory should be a strongly stabilizing factor in food
      webs. Working with an arthropod assemblage at Mount Saint Helens, I
      experimentally addressed this controversy using a two-way factorial design that
      crossed a manipulation of the degree of omnivory with another "disturbance"
      manipulation that targeted a specific component of the assemblage. In this
      statistical design, significant interaction effects (i.e., how the community
      impacts of the disturbance varied with the degree of omnivory) identified key
      stabilizing or destabilizing influences of omnivory. Overall, my experimental
      results indicated that increasing the degree of omnivory stabilized community
      dynamics, in keeping with recent conceptual syntheses.

PMID- 18811301
TI  - Metapopulation extinction in fragmented landscapes: using bacteria and protozoa
      communities as model ecosystems.
AB  - Extinction is notoriously difficult to study because of the long timescales
      involved and the difficulty in ascertaining that extinction has actually
      occurred. The effect of habitat subdivision, or fragmentation, on extinction risk
      is even harder to study, as it requires copious replication of habitat patches on
      large spatial scales and control of area effects between treatments. I used
      simple small-scale communities of bacteria and protozoa to study extinction in
      response to habitat loss and habitat fragmentation. I studied several different
      community configurations, each with three trophic levels. Unlike most
      metapopulation studies (experimental as well as theoretical), which have tended
      to deal with inherently unstable species interactions, I deliberately used
      community configurations that were persistent in large stock cultures. I recorded
      the time to extinction of the top predator in single habitat patches of different
      sizes and in fragmented systems with different degrees of subdivision but the
      same amount of available habitat. Habitat loss reduced the time to extinction of
      isolated populations. Fragmented systems went extinct sooner than corresponding
      unfragmented (continuous) systems of the same overall size. Unfragmented
      populations persisted longer than fragmented systems (metapopulations) with or
      without dispersal corridors between subpopulations. In fact, fragmented systems
      where the fragments were linked by dispersal corridors went extinctly
      significantly sooner than those where subpopulations were completely isolated
      from each other. If these results extend to more "natural" systems, it suggests a
      need for caution in management programs that emphasize widespread establishment
      of wildlife corridors in fragmented landscapes.

PMID- 18811302
TI  - The effects of herbivory on paternal fitness in scarlet gilia: better moms also
      make better pops.
AB  - Whether plants can benefit from the direct effects of herbivory has been
      contentious among ecologists and evolutionary biologists. Although previous
      studies have provided experimental evidence of enhanced maternal fitness
      following herbivory in a natural system, an accurate depiction of plant-herbivore
      interactions must include the effects of herbivory on male as well as female
      fitness. Here we show that ungulate herbivory on scarlet gilia results in an
      increase in paternal as well as maternal fitness. This study represents the first
      evidence of overcompensation in a natural system where both paternal and maternal
      components of fitness have been assessed.

PMID- 18811303
TI  - Currencies for foraging based on energetic gain.
AB  - We carry out a theoretical investigation of the behavior of a foraging animal
      that maximizes either the net amount of energy obtained (self-feeding) or the
      amount of energy delivered to another animal such as its young or to a store
      (provisioning). Using an novel graphical approach, we derive general results
      concerning the effects of constraints on the amount of energy the animal can
      spend or acquire. In the context of an animal that is provisioning, that is, both
      feeding itself and delivering energy to a given location, we establish a general
      relationship between the best foraging option when feeding itself and the best
      option to use when delivering energy. Our results extend and unify previous
      results in this area.

PMID- 18811304
TI  - The evolution of self-fertilization in perennials.
AB  - Many plants are perennials, but studies of self-fertilization do not usually
      include features of perennial life histories. We therefore develop models that
      include selfing, a simple form of perenniality, adult inbreeding depression, and
      an adult survivorship cost to seed production. Our analysis shows that inbreeding
      depression in adults diminishes the genetic transmission advantage associated
      with selfing, especially in long-lived perennials that experience inbreeding
      depression over many seasons. Perennials also pay a cost when selfing increases
      total seed set at the expense of future survivorship and reproduction. Such life
      history considerations shed new light on the generalization that annuals self
      fertilize more than perennials. Past research suggested reproductive assurance as
      an explanation for this association, but common modes of selfing offer equal
      reproductive assurance to annuals and perennials. Instead, perennials may avoid
      selfing because of adult inbreeding depression and the cost to future
      survivorship and reproduction.

PMID- 18811305
TI  - The evolution of indicator traits for parental quality: the role of maternal and
      paternal effects.
AB  - In systems where individuals provide material resources to their mates or
      offspring, mate choice based on traits that are phenotypically correlated with
      the quality of resources provided is expected to be adaptive. Several models have
      explored the evolution of mating preference where there are direct benefits to
      choice, but few have addressed how a phenotypic correlation can be established
      between a male indicator trait and the degree of parental investment. We present
      a model with three quantitative traits: male and female parental investment and a
      potential male indicator trait. In our model, the expression of the "indicator"
      trait in offspring is affected by parental investment. These effects are referred
      to as maternal or paternal effects, or as "indirect genetic effects" when
      parental investment is heritable. With genetic variation for degree of parental
      investment, offspring harbor genes for parental investment that are unexpressed
      before mating but will affect the investment that they provide when expressed.
      Because the investment received from the parents affects the expression of the
      indicator trait, there will be a correlation between the genes for parental
      investment inherited and the degree of expression of the indicator trait in the
      offspring. The indicator trait is thus an "honest" signal for the degree of
      paternal investment.

PMID- 18811306
TI  - The effects of conspecific attraction and habitat quality on habitat selection in
      territorial birds (Troglodytes aedon).

PMID- 18811307
TI  - Introduction: multilevel selection theory comes of age.

PMID- 18811308
TI  - Impact of the human egalitarian syndrome on darwinian selection mechanics.
AB  - With nothing more than kin selection and reciprocal altruism theories to work
      with, the selection basis of human degrees of altruism and cooperation is often
      difficult to explain. However, during our prehistoric foraging phase, a highly
      stable egalitarian syndrome arose that had profound effects on Darwinian
      selection mechanics. The band's insistence on egalitarianism seriously damped
      male status rivalry and thereby reduced the intensity of selection within the
      group by reducing phenotypic variation at that level, while powerful social
      pressure to make decisions consensual at the band level had a similar effect.
      Consensual decisions also had another effect: they increased variation between
      groups because entire bands enacted their subsistence strategies collectively and
      the strategies varied between bands. By reducing the intensity of individual
      selection and boosting group effects, these behaviors provided a unique
      opportunity for altruistic genes to be established and maintained. In addition,
      the egalitarian custom of socially isolating or actively punishing lazy or
      cheating noncooperators reduced the free-rider problem. In combination, these
      phenotypic effects facilitated selection of altruistic genes in spite of some
      limited free riding. This selection scenario remained in place for thousands of
      generations, and the result was a shift in the balance of power between
      individual and group selection in favor of group effects. This new balance today
      is reflected in an ambivalent human nature that exhibits substantial altruism in
      addition to selfishness and nepotism.

PMID- 18811309
TI  - Altruism and organism: disentangling the themes of multilevel selection theory.
AB  - The evolution of groups into adaptive units, similar to single organisms in the
      coordination of their parts, is one major theme of multilevel selection theory.
      Another major theme is the evolution of altruistic behaviors that benefit others
      at the expense of self. These themes are often assumed to be strongly linked,
      such that altruism is required for group-level adaptation. Multilevel selection
      theory reveals a more complex relationship between the themes of altruism and
      organism. Adaptation at every level of the biological hierarchy requires a
      corresponding process of natural selection, which includes the fundamental
      ingredients of phenotypic variation, heritability, and fitness consequences.
      These ingredients can exist for many kinds of groups and do not require the
      extreme genetic variation among groups that is usually associated with the
      evolution of altruism. Thus, it is reasonable to expect higher-level units to
      evolve into adaptive units with respect to specific traits, even when their
      members are not genealogically related and do not behave in ways that are
      obviously altruistic. As one example, the concept of a group mind, which has been
      well documented in the social insects, may be applicable to other species.

PMID- 18811310
TI  - Honey bee colonies are group-level adaptive units.
AB  - It is not widely recognized that natural selection has produced adaptive units at
      the level of groups. Multilevel selection theory shows that groups can evolve a
      high level of functional organization when between-group selection predominates
      over within-group selection. Strong empirical evidence that natural selection has
      produced adaptive units at the group level comes from studies of social insects
      in which we find colonies in certain species functioning as highly integrated
      units. The functional organization of a social insect colony is best understood
      for honey bees. Recent experimental analyses of honey bee colonies have revealed
      striking group-level adaptations that improve the foraging efficiency of
      colonies, including special systems of communication and feedback control. These
      findings are reviewed with the aim of showing that evolution has produced
      adaptively organized entities at the group level.

PMID- 18811311
TI  - Reproductive bribing and policing as evolutionary mechanisms for the suppression
      of within-group selfishness.
AB  - We show that a new, simple, and robust general mechanism for the social
      suppression of within-group selfishness follows from Hamilton's rule applied in a
      multilevel selection approach to asymmetrical, two-person groups: If it pays a
      group member to behave selfishly (i.e., increase its share of the group's
      reproduction, at the expense of group productivity), then its partner will
      virtually always be favored to provide a reproductive "bribe" sufficient to
      remove the incentive for the selfish behavior. The magnitude of the bribe will
      vary directly with the number of offspring (or other close kin) potentially
      gained by the selfish individual and inversely with both the relatedness r
      between the interactants and the loss in group productivity because of
      selfishness. This bribe principle greatly extends the scope for cooperation
      within groups. Reproductive bribing is more likely to be favored over social
      policing for dominants rather than subordinates and as intragroup relatedness
      increases. Finally, analysis of the difference between the group optimum for an
      individual's behavior and the individual's inclusive fitness optimum reveals a
      paradoxical feedback loop by which bribing and policing, while nullifying
      particular selfish acts, automatically widen the separation of individual and
      group optima for other behaviors (i.e., resolution of one conflict intensifies
      others).

PMID- 18811312
TI  - Evolution of the individual.
AB  - This article studies the transition in evolution from single cells to
      multicellular organisms as a case study in the origin of individuality. The
      issues considered are applicable to all major transitions in the units of
      selection that involve the emergence of cooperation and the regulation of
      conflict. Explicit genetic models of mutation and selection both within and
      between organisms are studied. Cooperation among cells increases when the fitness
      covariance at the level of the organism overcomes within-organism change toward
      defection. Selection and mutation during development generate significant levels
      of within-organism variation and lead to variation in organism fitness at
      equilibrium. This variation selects for gem-line modifiers and other mediators of
      within-organism conflict, increasing the heritability of fitness at the organism
      level. The evolution of these modifiers is the first new function at the emerging
      organism level and a necessary component of the evolution of individuality.

PMID- 18811313
TI  - Experimental studies of group selection: what do they tell us about group
      selection in nature?
AB  - The study of group selection has developed along two autonomous lines. One
      approach, which we refer to as the adaptationist school, seeks to understand the
      evolution of existing traits by examining plausible mechanisms for their
      evolution and persistence. The other approach, which we refer to as the genetic
      school, seeks to examine how currently acting artificial or natural selection
      changes traits within populations and focuses on current evolutionary change. The
      levels of selection debate lies mainly within the adaptationist school, whereas
      the experimental studies of group selection lie within the genetic school.
      Because of the very different traditions and goals of these two schools, the
      experimental studies of group selection have not had a major impact on the group
      selection debate. We review the experimental results of the genetic school in the
      context of the group selection controversy and address the following questions:
      Under what conditions is group selection effective? What is the genetic basis of
      a response to group selection? How common is group selection in nature?

PMID- 18811314
TI  - Models of symbiosis.
AB  - A tentative outline of concepts is proposed for the evolutionary genetics of
      symbiosis. There are three main topics. The first concerns the tension between
      the integrative and disruptive forces of kin selection. Kin selection can be
      disruptive because competition among close relatives favors dispersal and a
      reduction in relatedness among neighbors. Kin selection acts independently within
      each species of a symbiotic community but has important consequences for the
      integration of the community into a cooperative unit. The second topic describes
      the evolution of beneficial, synergistic effects between species. The evolution
      of mutual effects depends on various correlations between species. Genetic
      correlations are analogous to linkage disequilibrium in standard Mendelian
      genetics. Correlations in reproductive success between symbiotic partners arise
      from codispersal and reproductive synchrony. The third topic concerns the
      evolution of asymmetrical symbioses in which one species can dominate its
      partner. Dominance may explain the evolution of uniparental inheritance among
      cytoplasmic symbionts and a peculiar form of germ-soma separation in the
      symbionts of insects.

PMID- 18811315
TI  - Cooperation, conflict, and creching behavior in goldeneye ducks.
AB  - Creching behavior, or brood amalgamation, results in offspring being reared by
      adults other than their genetic parents. Although a variety of hypotheses have
      been proposed to explain this behavior, most assume either that brood
      amalgamation is accidental (i.e., nonselected) or that adoption of young is
      selected for because of social benefits to the young and/or adopting parents. We
      propose, instead, that brood amalgamation is a function of two separate
      processes: brood desertion and brood adoption. To examine brood desertion, we
      develop a graphic model to predict when parents should abandon their young and we
      test this model experimentally for the Barrow's goldeneye (Bucephala islandica).
      As predicted, females deserted their offspring when the size of the brood was
      experimentally reduced. Brood adoption occurred when deserted ducklings joined
      other broods. However, the success of ducklings in doing so was strongly
      dependent on the availability of potential host broods and on the age of the
      recipient broods. Foreign ducklings were readily accepted into young broods (<10
      d old) but invariably were rejected from old broods. We could detect no benefits
      or costs of brood adoption to the host females, contrary to the expectations of a
      social benefit hypothesis. Our experiments indicate that Creching behavior is
      driven by selection on adults to abandon their brood when the benefits of
      continued investment are outweighed by the reduction in future reproduction and
      selection on deserted ducklings to join other broods to obtain parental care.
      Rather than a form of cooperative brood care, Creching in goldeneyes is perhaps
      best considered as a form of reproductive parasitism, entailing parent-offspring
      conflict over brood desertion and intergenerational conflict over adoption of
      abandoned young.

PMID- 18811316
TI  - Nonsiblicidal behavior and the evolution of clutch size in bethylid wasps.
AB  - Parent-offspring conflict over clutch size may lead to siblicidal behavior
      between juveniles. In parasitoid wasps, selection for siblicide in small broods
      is predicted to produce a dearth of gregarious broods with few eggs. Here we
      document the clutch size distribution in the Bethylidae, a large family of
      aculeate parasitoids. Small gregarious clutches are the most common. Further data
      suggest that the most common gregarious clutches in the parasitoid Hymenoptera as
      a whole contain only a few eggs. Across bethylid species, both clutch size and
      wasp size increase with host size. Within genera clutch size is more closely
      related to host size, but between genera or larger clades wasp size is more
      closely related to host size. The volume of the emerging wasp brood does not
      depend on whether a species lays single- or multiple-egg clutches once host size
      is taken into account. These data suggest that clutch size in bethylid wasps is
      best described by traditional optimality models and that siblicide plays little
      role in this and possibly other families. We propose several ecological reasons
      for the rarity of siblicide in bethylids: ectoparasitism, idiobiosis, and a suite
      of characteristics associated with high within-brood relatedness.

PMID- 18811317
TI  - Noise and nonlinearity in measles epidemics: combining mechanistic and
      statistical approaches to population modeling.
AB  - We present and evaluate an approach to analyzing population dynamics data using
      semimechanistic models. These models incorporate reliable information on
      population structure and underlying dynamic mechanisms but use nonparametric
      surface-fitting methods to avoid unsupported assumptions about the precise form
      of rate equations. Using historical data on measles epidemics as a case study, we
      show how this approach can lead to better forecasts, better characterizations of
      the dynamics, and a better understanding of the factors causing complex
      population dynamics relative to either mechanistic models or purely descriptive
      statistical time-series models. The semimechanistic models are found to have
      better forecasting accuracy than either of the model types used in previous
      analyses when tested on data not used to fit the models. The dynamics are
      characterized as being both nonlinear and noisy, and the global dynamics are
      clustered very tightly near the border of stability (dominant Lyapunov exponent
      lambda approximately 0). However, locally in state space the dynamics oscillate
      between strong short-term stability and strong short-term chaos (i.e., between
      negative and positive local Lyapunov exponents). There is statistically
      significant evidence for short-term chaos in all data sets examined. Thus the
      nonlinearity in these systems is characterized by the variance over state space
      in local measures of chaos versus stability rather than a single summary measure
      of the overall dynamics as either chaotic or nonchaotic.

PMID- 18811318
TI  - Environmental stochasticity and extinction risk in a population of a small
      songbird, the great tit.
AB  - Using a long-term demographic data set, we estimated the separate effects of
      demographic and environmental stochasticity in the growth rate of the great tit
      population in Wytham Wood, United Kingdom. Assuming logistic density regulation,
      both the demographic (sigma2d = 0.569) and environmental (sigma2e = 0.0793)
      variance, with interactions included, were significantly greater than zero. The
      estimates of the demographic variance seemed to be relatively insensitive to the
      length of the study period, whereas reliable estimates of the environmental
      variance required long time series (at least 15 yr of data). The demographic
      variance decreased significantly with increasing population density. These
      estimates are used in a quantitative analysis of the demographic factors
      affecting the risk of extinction of this population. The very long expected time
      to extinction of this population (approximately 10(19) yr) was related to a
      relatively large population size (>/=120 pairs during the study period). However,
      for a given population size, the expected time to extinction was sensitive to
      both variation in population growth rate and environmental stochasticity.
      Furthermore, the form of the density regulation strongly affected the expected
      time to extinction. Time to extinction decreased when the maximum density
      regulation approached K. This suggests that estimates of viability of small
      populations should be given both with and without inclusion of density
      dependence.

PMID- 18811319
TI  - The value of being a resource specialist: behavioral support for a neural
      hypothesis.
AB  - The neural hypothesis of diet breadth proposes that selecting an appropriate
      behavior is more efficient if simple or exaggerated cues can be used as a basis
      of decision making rather than making a choice among many complex sensory inputs.
      I propose that simple signals overcome the problem of multiple sensory inputs and
      the consequent need for the brain to decide among inputs from these multiple
      channels. Experiments on grasshoppers show that there is a significant time cost
      in having to make a choice, relative to situations in which individuals have
      grown accustomed to having no choice. Those with a choice were shown to be less
      decisive by two different measures than those without a choice. It is argued that
      the data, showing lengthy decision times as a result of having a choice, would
      involve a significant ecological risk. It is further argued that the reduced risk
      of quick decisions would favor specialization of resource use. The evolution of
      resource-specific cues that have often been called sign stimuli are considered
      critical elements of restricted resource use.

PMID- 18811320
TI  - Competition intensity along a productivity gradient in a low-diversity grassland.
AB  - Competition among plants often shifts from roots to shoots as productivity
      increases and species composition changes. We examined competition in an old
      field with low diversity to test whether this shift occurred along a productivity
      gradient without species turnover. Forty plots received one of four nitrogen
      treatments (0, 5, or 15 g added N m-2 yr-1 or 400 g m-2 yr-1 of sawdust added to
      immobilize N) annually for 5 yr. All N levels were dominated by the perennial
      grasses Agropyron cristatum and Bromus inermis. Transplants of Agropyron were
      grown with all neighbors, roots of neighbors, or no neighbors present to measure
      total, root, and shoot competition. Transplant growth was 22%-165% higher in
      subplots without neighbors present, which indicates that competition occurred.
      Competition from neighbor roots was primarily responsible for suppression of
      transplant growth over the entire productivity gradient. In contrast to previous
      field experiments that found either an increase in total competition intensity or
      a shift from root to shoot competition with increasing productivity, we found
      neither. Increases in total competition intensity or shifts from root to shoot
      competition found along other gradients may be caused by changes in species
      composition and not by increased resources or neighbor biomass. These results
      suggest that different competitive mechanisms may operate in low-diversity
      vegetation than in more diverse natural vegetation.

PMID- 18811321
TI  - Trade-offs between reproductive traits and the influence of food intake during
      pregnancy in the garter snake, Thamnophis elegans.

PMID- 18811322
TI  - Scaling of gelatinous clutches: effects of siblings' competition for oxygen on
      clutch size and parental investment per offspring.
AB  - Theories on the evolution of clutch size are primarily influenced by examples
      from terrestrial animals, yet most animal phyla occur exclusively in water.
      Oxygen has a lower diffusion coefficient and lower solubility in water than in
      air, and siblings in aquatic clutches often compete for oxygen. Mitigating this
      competition could affect allocation of resources to offspring. Gelatinous
      clutches are common in aquatic habitats and have evolved multiple times in many
      phyla. We hypothesized that spacing of embryos by gel enhances delivery of oxygen
      but that gel is organically costly. A model of diffusion predicts that clutch
      thickness should scale inversely with the square root of embryo concentration,
      indicating a need to reduce embryo concentration (and increase gel volume)
      disproportionately with increasing clutch thickness. For embryos in artificial
      clutches constructed with agarose gel, development was faster in clutches with
      more gel per embryo, as predicted. For natural gelatinous clutches of gastropods,
      thick clutches had disproportionately larger volumes of gel and
      disproportionately more organic material invested in gel relative to embryos.
      Thus, for aquatic gelatinous clutches, requirements for oxygen supply can affect
      trade-offs involving clutch thickness and parental investment per offspring:
      resources are diverted to gel, and the proportion diverted increases with clutch
      thickness.

PMID- 18811323
TI  - A latitudinal gradient in northeast Pacific intertidal community structure:
      evidence for an oceanographically based synthesis of marine community theory.
AB  - Intertidal systems have been models for the study of the roles of competition,
      predation, and disturbance in determining community structure. These systems
      exhibit considerable regional variability in percentage cover and in the strength
      of interspecific interactions, which may be due largely to effects of varying
      larval supply. In Oregon and Washington, experimental studies of space allocation
      among sessile invertebrates have emphasized the role of benthic processes such as
      competition and predation. In contrast, studies in central California have
      emphasized the importance of larval supply. In this article, we identify a
      gradient in percentage cover in the middle and upper intertidal zone that is
      consistent with an oceanographically based explanation for these differences:
      percentage cover of mussels and barnacles is much higher in Oregon, where
      nearshore circulation promotes high recruitment, than in California, where strong
      offshore currents inhibit recruitment. A mathematical model incorporating larval
      transport and interspecific competition for space offers an explanation for the
      one violation of the hypothesis-higher percentage cover of Chthamalus spp. in
      California. The findings illustrate that attempts to synthesize regional
      differences in community structure and dynamics can benefit from considering both
      the benthic adult and pelagic larval environments.

PMID- 18811324
TI  - Direct and indirect effects of predation and predation risk in old-field
      interaction webs.
AB  - Indirect effects emerge when a change in the abundance of one species indirectly
      affects another by changing the abundances of intermediate species-called density
      mediated indirect effects-or they arise when one species modifies how two other
      species interact-called trait-mediated indirect effects. I report on field
      experiments that evaluated how grass and herb biomass in old-field interaction
      webs was influenced indirectly by a spider carnivore through its interactions
      with a generalist and a grass-specialist grasshopper species. I manipulated
      interaction pathways between the spider and the plants using different
      combinations of the grasshopper species. I changed the modality of predator-prey
      interactions to isolate density-mediated from trait-mediated effects using
      natural spiders (predation spiders) or spiders that were prevented from subduing
      prey by mouthpart manipulation (risk spiders). I found that indirect effects were
      stronger in speciose, reticulate food webs than in linear food chains owing to a
      trait-mediated effect, a diet shift by herbivores in response to predation risk.
      Spiders alone did not have significant effects on grasshopper densities in the
      field experiments, removing any possibility of density-mediated indirect effects.
      The study illustrates that ecologists should not underestimate the importance of
      behavioral ecology in determining community-level interactions.

PMID- 18811325
TI  - The acquisition of hypovirulence in host-pathogen systems with three trophic
      levels.
AB  - A major focus of research on the dynamics of host-pathogen interactions has been
      the evolution of pathogen virulence, which is defined as the loss in host fitness
      due to infection. It is usually assumed that changes in pathogen virulence are
      the result of selection to increase pathogen fitness. However, in some cases,
      pathogens have acquired hypovirulence by themselves becoming infected with
      hyperparasites. For example, the chestnut blight fungus Cryphonectria parasitica
      has become hypovirulent in some areas by acquiring a double-stranded RNA
      hyperparasite that debilitates the pathogen, thereby reducing its virulence to
      the host. In this article, we develop and analyze a mathematical model of the
      dynamics of host-pathogen interactions with three trophic levels. The system may
      be dominated by either uninfected (virulent) or hyperparasitized (hypovirulent)
      pathogens, or by a mixture of the two. Hypovirulence may allow some recovery of
      the host population, but it can also harm the host population if the
      hyperparasite moves the transmission rate of the pathogen closer to its
      evolutionarily stable strategy. In the latter case, the hyperparasite is
      effectively a mutualist of the pathogen. Selection among hyperparasites will
      often minimize the deleterious effects, or maximize the beneficial effects, of
      the hyperparasite on the pathogen. Increasing the frequency of multiple
      infections of the same host individual promotes the acquisition of hypovirulence
      by increasing the opportunity for horizontal transmission of the hyperparasite.
      This effect opposes the usual theoretical expectation that multiple infections
      promote the evolution of more virulent pathogens via selection for rapid growth
      within hosts.

PMID- 18811326
TI  - A game theoretical model of the evolution of food hoarding: applications to the
      Paridae.
AB  - A game against the field is proposed that models the evolution of food-hoarding
      behavior in a group-living species, like many members of the family Paridae
      (Aves, Passeriformes). The model predicts that no special retrieval mechanisms
      (e.g., memory) are necessary for food-hoarding individuals to invade a population
      of nonhoarders, as long as the winters are very severe. Once food hoarding is
      established in a population, having smaller groups and separating foraging niches
      between group members prevent cheaters from benefiting from other individuals'
      caches. A scenario is proposed for the evolution of hoarding in the Paridae.

PMID- 18811327
TI  - Female mate preference to maximize paternal care. II. Female competition leads to
      monogamy.
AB  - A two-step game model of female mate preference and paternal care is examined,
      with a particular focus on the case of two females and two males. In a mating
      season, females choose their mates, and in the following breeding season males
      invest in paternal care, knowing the likelihood of their paternity in chicks. If
      parental ability is the same between individuals of each sex, the evolutionarily
      stable mating pattern is always monogamy. If females differ in fecundity and
      males differ in paternal care capacity, monogamy with assortative mating is
      likely to be evolutionarily stable. If the male cost function increases at a
      strongly accelerating rate, however, polyandry is evolutionarily stable when the
      difference of female fecundity is very large, but the game may have no
      evolutionarily stable state when the difference of female fecundity is small. The
      care graph (in which females are connected to males giving paternal care to their
      chicks) is often much simpler than the mating graph (in which females are
      connected to males they accepted). To be exact, no "loop" should be included in
      the evolutionarily stable care graph for the general case of n females and m
      males. This prediction is in accord with the observed prevalence of social
      monogamy in spite of genetic promiscuity among altricial birds.

PMID- 18811328
TI  - Parasites, pathogens, and polyandry in social insects.

PMID- 18811329
TI  - Parasites, pathogens, and polyandry in honey bees.

PMID- 18811330
TI  - The light: nutrient ratio in lakes: the balance of energy and materials affects
      ecosystem structure and process.
AB  - The amounts of solar energy and materials are two of the chief factors
      determining ecosystem structure and process. Here, we examine the relative
      balance of light and phosphorus in a set of freshwater pelagic ecosystems. We
      calculated a ratio of light: phosphorus by putting mixed-layer mean light in the
      numerator and total P concentration in the denominator. This light: phosphorus
      ratio was a good predictor of the C:P ratio of particulate matter (seston), with
      a positive correlation demonstrated between these two ratios. We argue that the
      balance between light and nutrients controls "nutrient use efficiency" at the
      base of the food web in lakes. Thus, when light energy is high relative to
      nutrient availability, the base of the food web is carbon rich and phosphorus
      poor. In the opposite case, where light is relatively less available compared to
      nutrients, the base of the food web is relatively P rich. The significance of
      this relationship lies in the fact that the composition of sestonic material is
      known to influence a large number of ecosystem processes such as secondary
      production, nutrient cycling, and (we hypothesize) the relative strength of
      microbial versus grazing processes. Using the central result of increased C:P
      ratio with an increased light: phosphorus ratio, we make specific predictions of
      how ecosystem structure and process should vary with light and nutrient balance.
      Among these predictions, we suggest that lake ecosystems with low light:
      phosphorus ratios should have several trophic levels simultaneously carbon or
      energy limited, while ecosystems with high light: phosphorus ratios should have
      several trophic levels simultaneously limited by phosphorus. Our results provide
      an alternative perspective to the question of what determines nutrient use
      efficiency in ecosystems.

PMID- 18811331
TI  - Host heterogeneity in susceptibility and disease dynamics: tests of a
      mathematical model.
AB  - Most mathematical models of disease assume that transmission is linearly
      dependent on the densities of host and pathogen. Recent data for animal diseases,
      however, have cast doubt on this assumption, without assessing the usefulness of
      alternative models. In this article, we use a combination of laboratory dose
      response experiments, field transmission experiments, and observations of
      naturally occurring populations to show that virus transmission in gypsy moths is
      a nonlinear function of virus density, apparently because of heterogeneity among
      individual gypsy moth larvae in their susceptibility to the virus. Dose-response
      experiments showed that larvae from a laboratory colony of gypsy moths are
      substantially less heterogeneous in their susceptibility to the virus than are
      larvae from feral populations, and field experiments showed that there is a more
      strongly nonlinear relationship between transmission and virus density for feral
      larvae than for lab larvae. This nonlinearity in transmission changes the
      dynamics of the virus in natural populations so that a model incorporating host
      heterogeneity in susceptibility to the virus gives a much better fit to data on
      virus dynamics from large-scale field plots than does a classical model that
      ignores host heterogeneity. Our results suggest that heterogeneity among
      individuals has important effects on the dynamics of disease in insects at
      several spatial and temporal scales and that heterogeneity in susceptibility may
      be of general importance in the ecology of disease.

PMID- 18811332
TI  - Parental environmental effects and cyclical dynamics in plant populations.
AB  - Parental environmental effects have been widely reported in plants, but these
      effects are often weak relative to direct effects of current environmental
      conditions. Few studies have asked when consideration of such effects is
      necessary to understand long-term plant population dynamics. In this article, I
      show that inclusion of effects of parental density on offspring mass
      fundamentally changes population dynamics models by making recruitment a function
      of population size in two previous generations (Nt+1 = f(Nt, Nt-1)), rather than
      one (Nt+1 = f(Nt,)). Models without parental density effects predict either
      stable population dynamics or sharp crashes from high to low population size
      (flip bifurcations). When parental effects are at least one-third the size of
      direct density effects, gradual cycles from high to low population size (Hopf
      bifurcations) are possible. In this study, I measured effects of parental and
      offspring density on offspring quality in an annual plant, Cardamine
      pensylvanica, by manipulating plant density independently in parent and offspring
      generations and by comparing the effects of parent and offspring density on
      offspring performance. Parental density effects were detectable but were
      noticeably weaker than offspring density effects. Nonetheless, the parental
      effect was large enough to change population dynamics predictions. Thus, parental
      effects may be an important component of the numerical dynamics of plant
      populations.

PMID- 18811333
TI  - Plant polyploidy and insect/plant interactions.
AB  - We used flow cytometry and extensive geographic surveys of herbivore attack to
      test whether repeated evolution of autotetraploidy in the perennial herb Heuchera
      grossulariifolia Rydb. (Saxifragaceae) has created evolutionary barriers to
      attack by the specialist moth herbivore Greya politella (Prodoxidae). We found
      that the moth has colonized tetraploid as well as diploid populations, has
      colonized tetraploids of separate evolutionary origin, and, at least under some
      conditions, is more likely to attack tetraploids than diploids. Plant polyploidy
      therefore provides a potential route out of specialization as an evolutionary
      dead end in phytophagous insect taxa as well as a potentially important route to
      subsequent phylogenetic and geographic diversification of plant/insect
      interactions.

PMID- 18811334
TI  - Clutch-size behavior and coexistence in ephemeral-patch competition models.
AB  - Systems of patchy, ephemeral resources often support surprisingly diverse
      assemblages of consumer insects. Aggregation of consumer individuals over the
      landscape of patches has been suggested as one mechanism that can stabilize
      competition among consumer species. One mechanism for larval aggregation is the
      laying of eggs in clutches by females traveling among patches to distribute their
      total fecundity. We use simulation models to explore the consequences, for
      coexistence of competitors, of larval aggregation that arises from clutch laying.
      Contrary to some previous treatments, we find that clutch laying can be strongly
      stabilizing and under certain conditions can be sufficient to allow competitors
      to coexist stably. We extend these models by considering clutch size as a
      variable that responds to the abundance of resource patches. Such a relationship
      might be expected because females should lay their eggs in fewer but larger
      clutches when the cost of travel among patches is high (because patches are
      rare). When females adjust clutch size in response to resource abundance,
      coexistence can be easiest when resource patches are scarce and most difficult
      when resources are abundant.

PMID- 18811335
TI  - Survival rates of tropical and temperate passerines: a Trinidadian perspective.
AB  - Mark-recapture data collected using mist nets over a 10-yr period in Trinidad
      were used to estimate adult survival rates for 17 species of forest passerines.
      Trinidadian survival rates (mean 65%, range 45%-85%) were significantly higher
      than published estimates for European (mean survival 52%, range 32%-71%) and
      North American (mean survival 53%, range 29%-63%) passerines of similar body size
      (equivalent to 45% higher mean life expectancy in Trinidad). These findings were
      confirmed after controlling for phylogeny using a method of independent
      contrasts. Transient and/or young birds were an important feature of the Trinidad
      data, and studies that fail to allow for the presence of such birds risk
      underestimating adult survival. This study lends support to the hypothesis that
      avian survival rates are higher in the humid tropics, although the magnitude of
      the difference may be smaller than previously suggested.

PMID- 18811336
TI  - Altruist cheater dynamics in Dictyostelium: aggregated distribution gives stable
      oscillations.

PMID- 18811337
TI  - Effect size in ecological experiments: the application of biological models in
      meta-analysis.

PMID- 18811341
TI  - Intrapopulation sex ratio variation in the salt grass Distichlis spicata.
AB  - ABSTRACT In many dioecious plant populations, males and females appear to be
      spatially segregated, a pattern that is difficult to explain given its
      potentially high costs. However, in asexually propagating species, spatial
      segregation of the sexes may be indistinguishable from superficially similar
      patterns generated by random establishment of a few genets followed by extensive
      clonal spread and by gender-specific differences in rates of clonal spread. In
      populations where a significant fraction of individuals are not flowering and
      gender cannot be assigned to this fraction, apparent spatial segregation of the
      sexes may be due to differential flowering between the sexes. We confirm reports
      that flowering ramets of the clonal, perennial grass Distichlis spicata are
      spatially segregated by sex. We extend these studies in two fundamental ways and
      demonstrate that this species exhibits true spatial segregation of the sexes.
      First, using RAPD markers, we estimated that at least 50% of ramets in patches
      with biased sex ratios represent distinct genotypes. Second, we identified a RAPD
      marker linked to female phenotype (eliminating the possibility that gender is
      environmentally determined) and used it to show that the majority of patches
      exhibit significantly biased sex ratios for both ramets and genets, regardless of
      flowering status.

PMID- 18811342
TI  - Frequency-dependent pollen discounting contributes to maintenance of a mixed
      mating system in the common morning glory Ipomoea purpurea.
AB  - Pollen discounting, a reduction in outcross success associated with increased
      selfing, was evaluated in the common morning glory Ipomoea purpurea. A field
      experiment was conducted to estimate selfing rates and outcross success using
      small arrays of plants with large or small anther-stigma distance (ASD). To
      evaluate the effect of genotypic composition on the mating-system parameters,
      arrays were composed of five different frequencies of small- and large-ASD
      genotypes. While the selfing rates of genotypes with small ASD were consistently
      higher than genotypes with large ASD regardless of the genotypic frequency,
      outcross success was negatively frequency dependent. The genotype that was at
      lower frequency in the array had higher outcrossing success in three out of the
      four array types with unequal frequencies. This advantage-when-rare phenomenon
      can contribute to preventing the fixation of either extreme ASD-morph and
      maintaining a mixed mating system in I. purpurea.

PMID- 18811343
TI  - A clarification of pollen discounting and its joint effects with inbreeding
      depression on mating system evolution.
AB  - Given the predominance of outcrossing by angiosperms, large costs must often
      overwhelm the genetic benefit of selfing derived from contributing two haploid
      genomes to each off-spring rather than one. In addition to the well-studied
      genetic cost of inbreeding depression, selfing imposes a mating cost whenever
      self-pollination reduces opportunities for pollen export. Because self
      pollination is a heterogeneous process, pollen discounting and its evolutionary
      consequences vary with pollination conditions. In this article we model self
      pollination as comprising discounting and nondiscounting components, and we
      consider the consequences of this heterogeneity for outcross siring success.
      Aided by this depiction of pollination, we then compare previous theoretical
      representations of pollen discounting and consider their relative virtues.
      Finally, we consider conditions that would allow a population to be invaded by a
      variant with different pollination characteristics. This analysis exposes the
      pollination conditions implicit in standard results of mating system theory. It
      also identifies associations between four possible changes in pollination
      expected in different reproductive environments, including the incidence of
      positive or negative correlations between self-pollination and pollen export.
      These results emphasize the benefits of expanding the theory of plant
      reproduction to recognize explicitly when and how pollination mechanisms affect
      mating outcomes.

PMID- 18811344
TI  - Pollinator behavior and deceptive pollination: learning process and floral
      evolution.
AB  - Some species of flowering plants engage in nonmodel deceptive pollination,
      attracting pollinators by large nonmimetic floral displays and providing no
      reward. Pollinators can learn to avoid deceptive plants and to favor
      nectariferous species. The reproductive success of these species is expected to
      be density dependent for two opposite reasons: the commoner cheating flowers are,
      the easier they are to avoid and the lower the quality of the patch, making it
      more difficult to recognize that unrewarding flowers are not profitable. When a
      deceptive species is made up of multiple floral variants, pollinators' learning
      could decrease the reproductive success of any particularly common floral
      variant. Within a population of deceptive plants, mean reproductive success
      could, therefore, vary with the number of floral variants. We investigate these
      three hypotheses by modeling the behavior of pollinators foraging in communities
      of deceptive and rewarding flowers. Simulations revealed that the reproductive
      success of deceptive flowers varies in a density-dependent manner and that floral
      variants can be submitted to negative frequency-dependent selection. We compare
      density dependence in nonmodel deceptive species to what is expected in Batesian
      mimics and discuss possible selection of morphological variants. Finally, we
      survey how pollinators' learning capacities can make mean reproductive success
      depend on morphological variability within a population.

PMID- 18811345
TI  - On the evolution of premating isolation after a founder event.
AB  - We present a new simple model for the evolution of premating reproductive
      isolation. Using this model we first analyze the level of genetic variability
      maintained by mutation in a large stable population. Then we consider the
      plausibility of the evolution of strong premating reproductive isolation after a
      founder event. We demonstrate that after a founder event a new adaptive
      combination of genes may rise to high frequencies in the presence of an old
      combination of genes. We compare the probabilities of speciation after a founder
      event with those in a stable population and with those when reproductive
      isolation is due to viability selection against hybrids. We argue that premating
      reproductive isolation is more efficient than postmating reproductive isolation
      in maintaining the integrity of sympatric species. This might have contributed to
      the pattern of stronger premating isolation than postmating isolation between
      closely related pairs of sympatric species.

PMID- 18811346
TI  - Time and energy constraints in pinniped lactation.
AB  - Previous reviews have recognized patterns of lactation in pinnipeds divided along
      phylogenetic lines. This study extended previous models of lactation in pinnipeds
      by explicitly taking into account all the energetic costs to mothers. Based on an
      analysis of time-energy budgets, the feasible lactation strategy for a species
      can be shown to depend on body mass. Due to increased metabolic costs of
      maintenance, species with a large body mass cannot normally sustain lactation by
      foraging during lactation unless they have access to rich local prey resources.
      Consequently, large pinnipeds must normally sustain lactation from body reserves.
      This disadvantage is compensated in large pinnipeds by freedom to forage in
      support of offspring at greater range whereas small pinnipeds are restricted to
      foraging within the locality of the pupping colony. In the absence of
      correlations between major life-history variables and body mass in pinnipeds, the
      principal patterns of lactation are likely to be different solutions to the trade
      off between foraging on a relatively rich prey resource at long range and
      foraging on a poorer prey resource within a restricted range. Hence phylogeny may
      be less important than adaptation in the evolution of pinniped lactation.

PMID- 18811347
TI  - Models suggesting field experiments to test two hypotheses explaining
      successional diversity.
AB  - A simple mathematical model of competition is developed that includes two
      alternative mechanisms promoting successional diversity. The first underpins the
      competition-colonization hypothesis in which early successional species are able
      to persist because they colonize disturbed habitats before the arrival of late
      successional dominant competitors. The second underpins the niche hypothesis, in
      which early successional species are able to persist, even with unlimited
      colonization by late successional dominants, because they specialize on the
      resource-rich conditions typical of recently disturbed sites. We modify the
      widely studied competition-colonization model so that it also includes the
      mechanism behind the niche hypothesis. Analysis of this model suggests simple
      experiments that determine whether the successional diversity of a field system
      is maintained primarily by the competition-colonization mechanism, primarily by
      the niche mechanism, by neither, or by both. We develop quantitative metrics of
      the relative importance of the two mechanisms. We also discuss the implications
      for the management of biodiversity in communities structured by the two
      mechanisms.

PMID- 18811348
TI  - Experimental tests of the dependence of arthropod diversity on plant diversity.
AB  - Because a diversity of resources should support a diversity of consumers, most
      models predict that increasing plant diversity increases animal diversity. We
      report results of a direct experimental test of the dependence of animal
      diversity on plant diversity. We sampled arthropods in a well-replicated
      grassland experiment in which plant species richness and plant functional
      richness were directly manipulated. In simple regressions, both the number of
      species planted (log2 transformed) and the number of functional groups planted
      significantly increased arthropod species richness but not arthropod abundance.
      However, the number of species planted was the only significant predictor of
      arthropod species richness when both predictor variables were included in ANOVAs
      or a MANOVA. Although highly significant, arthropod species richness regressions
      had low R2 values, high intercepts (24 arthropod species in monocultures), and
      shallow slopes. Analyses of relations among plants and arthropod trophic groups
      indicated that herbivore diversity was influenced by plant, parasite, and
      predator diversity. Furthermore, herbivore diversity was more strongly correlated
      with parasite and predator diversity than with plant diversity. Together with
      regression results, this suggests that, although increasing plant diversity
      significantly increased arthropod diversity, local herbivore diversity is also
      maintained by, and in turn maintains, a diversity of parasites and predators.

PMID- 18811350
TI  - Sex allocation and the evolutionary transition between solitary and gregarious
      parasitoid development.

PMID- 18811349
TI  - Origin of chromosomes in response to mutation pressure.

PMID- 18811351
TI  - Developmental stability and fitness: the evidence is not quite so clear.

PMID- 18811352
TI  - Climate change disequilibrium of boreal permafrost peatlands caused by local
      processes.
AB  - Boreal forest and tundra are the biomes expected to experience the greatest
      warming during the course of the next century. The transient responses of boreal
      peatlands to climate change could be more complex than a simple large release of
      carbon and rapid migrations of vegetation and permafrost. Here we used
      alternative models to demonstrate that local processes typical of permafrost
      peatlands control carbon and vegetation dynamics in ways that strongly mediate
      effects of regional temperature gradients. Regional temperature affected
      stability and thaw rate. Thaw rate increased with mean annual temperature, and
      rates have accelerated within the last 50 yr. Local factors exerted a strong
      influence on stability, the levels of which were highest in three of the four
      temperature zones studied along the shaded south-southwest edges of collapse
      scars. The presence of Sphagnum fuscum cover increased stability. In all zones,
      survey points with S. fuscum showed more than twice the stability of points with
      feather moss, lichen, or no vegetation. In a direct model comparison between
      regional and local control, local factors were more important. Our results
      suggest that local processes mediate the effects of regional climate, and an
      accurate representation of ecosystem dynamics benefits from both local and
      regional processes.

PMID- 18811353
TI  - Optimal foraging, specialization, and a solution to Liem's paradox.
AB  - Species that appear highly specialized on the basis of their phenotype (e.g.,
      morphology, behavior, and physiology) also sometimes act as ecological
      generalists. This apparent paradox has been used to argue against the importance
      of competition as a diversifying evolutionary force. We provide an alternative
      explanation based on optimal foraging theory. Some resources are intrinsically
      easy to use and are widely preferred, while others require specialized phenotypic
      traits on the part of the consumer. This asymmetry allows optimally foraging
      consumers to evolve phenotypic specializations on nonpreferred resources without
      greatly compromising their ability to use preferred resources. The evolution of
      phenotypic specialization on nonpreferred resources can be driven by competition,
      but the specialists act as ecological generalists whenever their preferred
      resources are available. Our model identifies at least three different concepts
      of specialization that need to be distinguished, based on diet, prey utilization
      efficiencies, and phenotypic adaptations. The relationships among these concepts
      are complex and often counterintuitive. Specialists should often reject the very
      resources that they have evolved traits to use. The most extreme phenotypic
      specializations should occur in the absence of a trade-off between using
      preferred and nonpreferred resources. Our model may explain why extreme
      phenotypic-specializations evolve more often in fish communities than in
      terrestrial vertebrate communities and provides a mechanism whereby species can
      coexist in stable communities despite common preferences for some resources.

PMID- 18811354
TI  - Paternity and multiple signaling: effects of a secondary sexual character and
      song on paternity in the barn swallow.
AB  - Multiple signals may evolve because they provide independent information on the
      condition of a signaler. Females should pay attention to male characters relative
      to their reliability as signals of male attractiveness or quality. Since
      behavioral traits are flexible and, therefore, subject to strong environmental
      influences, females should weigh stable morphological signals higher in their
      choice of mates for genetic benefits than flexible behavioral traits, for
      example, by paying particular attention to phenotypically plastic traits when
      produced in combination with an exaggerated morphological signal. Consistent with
      this prediction, female barn swallows Hirundo rustica, which are known to prefer
      males with the longest tail feathers (a secondary sexual character), also
      preferred males with extreme expressions of a behavioral trait (song rate), as
      determined from patterns of paternity assessed by microsatellites. However, a
      statistical interaction between tail length and song rate implied that song rate
      was relatively unimportant for males with a short tail but more important for
      longtailed males. Since song rate is a flexible behavioral trait, females appear
      to have responded to this flexibility by devaluing the importance of song rate in
      assessment of unattractive sires.

PMID- 18811355
TI  - Reproductive roles in the cooperatively breeding acorn woodpecker: incest
      avoidance versus reproductive competition.
AB  - Incest is rare in the cooperatively breeding acorn woodpecker (Melanerpes
      formicivorus) despite a polygynandrous mating system in which nearly all group
      members are close relatives. Here we test the relative importance of avoiding
      matings between close relatives (incest avoidance) and within-sex competition for
      breeding opportunities (reproductive competition) in determining the mating
      system of acorn woodpeckers by examining how reproductive roles change following
      breeding vacancies. In 83% of cases in which helpers of the same sex were present
      in the group, reproductive vacancies were resolved when new unrelated immigrants
      filled the vacancy to the exclusion of resident same-sex helpers, who generally
      emigrated or did not breed while they remained in the group. Helpers of the
      opposite sex, especially when male, were significantly more likely to remain in
      their natal group and in about half the cases inherited and bred following
      reproductive vacancies. This result was not explainable by reproductive
      competition, since the number of immigrants was often less than or equal to the
      number of same-sex helpers in the group. Apparent incest resulted in 5% of cases.
      The time required to resolve reproductive vacancies was significantly longer for
      groups with helpers of the same sex as the vacancy. These results confirm that
      both incest avoidance and reproductive competition are important factors
      determining reproductive roles within groups of this highly social species.

PMID- 18811356
TI  - A general theory of environmental noise in ecological food webs.
AB  - We examine the effects of environmental noise on populations that are parts of
      simple two-species food webs. We assume that the species are strongly interacting
      and that one or the other population is affected by the noise signal. Further
      assuming that a stable equilibrium with positive population densities exists, we
      are able to perform a complete frequency analysis of the system. If only one of
      the populations is subject to noise, the relative noise response by both
      populations is fully determined by the sign of a single element of the Jacobian
      matrix. The analysis is readily extended to cases when both species are affected
      by noise or when the food web has more than two species. The general conclusion
      about relative responses to noise is then less unambiguous, but the power spectra
      describing the frequency composition of the population variabilities are
      nevertheless completely determined. These results are entirely independent on the
      exact nature of the interaction (i.e., predation, competition, mutualism) between
      the populations. The results show that the interpretation of the "color" of
      ecological time series (i.e., the frequency composition of population variability
      over time) may be complicated by species interactions. The propagation of noise
      signals through food webs and the importance of web structure for the expected
      response of all parts of the web to such signals is a challenging field for
      future studies.

PMID- 18811357
TI  - The statistical inevitability of stability-diversity relationships in community
      ecology.
AB  - In this article, we explain an often overlooked process that may significantly
      contribute to positive correlations between measures of species diversity and
      community stability. Empirical studies showing positive stability-diversity
      relationships have, for the most part, used a single class of stability (or, more
      accurately, instability) measures: the temporal variation in aggregate community
      properties such as biomass or productivity. We show that for these measures,
      stability will essentially always rise with species diversity because of the
      statistical averaging of the fluctuations in species' abundances. This simple
      probabilistic process will operate in the absence of any strong species
      interactions, although its strength is driven by the relative abundances of
      species, as well as by the existence of positive or negative correlations in the
      fluctuations of species. To explore the possible importance of this effect in
      real communities, we fit a simple simulation model to Tilman's grassland
      community. Our results indicate that statistical averaging might play a
      substantial role in explaining stability-diversity correlations for this and
      other systems. Models of statistical averaging can serve as a useful baseline for
      predictions of community stability, to which the influences of both negative and
      positive species interactions may then be added and tested.

PMID- 18811358
TI  - Diversity-stability relationships: statistical inevitability or ecological
      consequence?

PMID- 18811359
TI  - Differentiation of allelic frequencies at quantitative trait loci affecting
      locally adaptive traits.

PMID- 18811360
TI  - Predicting population trends from size distributions: a direct test in a tropical
      tree community.
AB  - Forest ecologists often evaluate how well the species composition of saplings in
      the understory matches that of the canopy: absence of juveniles suggests that a
      tree species is suffering population decline. Here we offer a theoretical and
      empirical test of this assertion using data from a 50-ha census plot in Panama.
      Theory indicates that higher rates of population change, lambda, lead to more
      steeply declining size distributions (more juveniles relative to adults). But
      other parameters also affect the size distribution: lower growth rate of
      juveniles and lower survival at any size produce more steeply declining size
      distributions as well. Empirical evaluation of 216 tree populations showed that
      juvenile growth was the strongest predictor of size distribution, in the
      direction predicted by theory. Size distribution did correlate with population
      growth, but weakly and only in understory species, not canopy species. Size
      distribution did not correlate with the growth rate of larger individuals nor
      with survival. Results suggest that static in formation on the size distribution
      is not a good predictor of future population trends, while demographic
      information is. Fast-growing species will have fewer juveniles in the understory
      than slow growing species, even when population growth is equal.

PMID- 18811361
TI  - Why more productive sites have more species: an experimental test of theory using
      tree-hole communities.
AB  - One of the most common explanations for an increase in species richness with
      productivity is what we have dubbed the "More Individuals Hypothesis." According
      to this hypothesis, more productive sites can support higher total abundances
      and, since species richness is an increasing function of total abundance, so will
      it be of productivity. This hypothesis assumes that communities are limited by
      productivity. We tested the More Individuals Hypothesis using the detritivorous
      aquatic insect communities of tree holes. When tree holes with varying levels of
      productivity (debris amount) were allowed to be colonized (through oviposition),
      more productive tree holes did have more species but not more individuals.
      Neither was total energy use strictly proportional to productivity. Only in
      communities forced to disassemble through productivity reductions were the
      predictions of the More Individuals Hypothesis satisfied. Ovipositing adults may
      prefer productive tree holes not because they contain more resources but because
      they are anticipated to be less likely to dry out. In tree holes, and more
      generally, the More Individuals Hypothesis is an insufficient explanation for
      increases in species richness with productivity because it neither accounts for
      the different processes of local colonization and extinction nor allows body size
      to correlate with extinction risk.

PMID- 18811362
TI  - Long-term dynamics in a metapopulation of the American pika.
AB  - A 20-yr study of a metapopulation of the American pika revealed a regional
      decline in occupancy in one part of a large network of habitat patches. We
      analyze the possible causes of this decline using a spatially realistic
      metapopulation model, the incidence function model. The pika metapopulation is
      the best-known mammalian example of a classical metapopulation with significant
      population turnover, and it satisfies closely the assumptions of the incidence
      function model, which was parameterized with data on patch occupancy. The model
      predicted incidences of patch occupancy are consistent with observed incidences,
      and the model predicts well the observed turnover rate between four
      metapopulation censuses. According to model predictions, the part of the
      metapopulation where the decline has been observed is relatively unstable and
      prone to large oscillations in patch occupancy, whereas the other part of the
      metapopulation is predicted to be persistent. These results demonstrate how
      extinction-colonization dynamics may produce spatially correlated patterns of
      patch occupancy without any spatially correlated processes in local dynamics or
      extinction rate. The unstable part of the metapopulation gives an empirical
      example of multiple quasi equilibria in metapopulation dynamics. Phenomena
      similar to those observed here may cause fluctuations in species' range limits.

PMID- 18811363
TI  - Optimal foraging and beyond: how starlings cope with changes in food
      availability.
AB  - Foraging adaptations include behavioral and physiological responses, but most
      optimal foraging models deal exclusively with behavioral decision variables,
      taking other dimensions as constraints. To overcome this limitation, we measured
      behavioral and physiological responses of European starlings Sturnus vulgaris to
      changes in food availability in a laboratory environment. The birds lived in a
      closed economy with a choice of two foraging modes (flying and walking) and were
      observed under two treatments (hard and easy) that differed in the work required
      to obtain food. Comparing the hard with the easy treatment, we found the
      following differences. In the hard treatment, daily amount of work was higher,
      but daily intake was lower. Even though work was greater, total daily expenditure
      was smaller, partly because overnight metabolism was lower. Body mass was lower,
      but daily oscillation in body mass did not differ. Feces' caloric density was
      lower, indicating greater food utilization. Energy expenditure rate expressed as
      multiples of basal metabolic rate (BMR) increased during the working period from
      3.5 x BMR (easy) to 5.2 x BMR (hard), but over the 24-h period, it was close to
      2.4 x BMR in both treatments. We also found that rate of expenditure during
      flight was very high in both treatments (52.3 W in easy and 45.5 W in hard), as
      expected for short (as opposed to cruising) flights. The relative preferences
      between walking and flying were incompatible with maximizing the ratio of energy
      gains per unit of expenditure (efficiency) but compatible with maximizing net
      gain per unit of time during the foraging cycle (net rate). Neither currency
      explained the results when nonforaging time was included. Time was not a direct
      constraint: the birds rested more than 90% of the time in both treatments.
      Understanding this complex picture requires reasoning with ecological,
      physiological, and cognitive arguments. We defend the role of optimality as an
      appropriate tool to guide this integrative perspective.

PMID- 18811364
TI  - Ecological biogeography of southern ocean islands: species-area relationships,
      human impacts, and conservation.
AB  - Previous studies have concluded that southern ocean islands are anomalous because
      past glacial extent and current temperature apparently explain most variance in
      their species richness. Here, the relationships between physical variables and
      species richness of vascular plants, insects, land and seabirds, and mammals were
      reexamined for these islands. Indigenous and introduced species were
      distinguished, and relationships between the latter and human occupancy variables
      were investigated. Most variance in indigenous species richness was explained by
      combinations of area and temperature (56%)-vascular plants; distance (nearest
      continent) and vascular plant species richness (75%)-insects; area and
      chlorophyll concentration (65%)-seabirds; and indigenous insect species richness
      and age (73%)-land birds. Indigenous insects and plants, along with distance
      (closest continent), explained most variance (70%) in introduced land bird
      species richness. A combination of area and temperature explained most variance
      in species richness of introduced vascular plants (73%), insects (69%), and
      mammals (69%). However, there was a strong relationship between area and number
      of human occupants. This suggested that larger islands attract more human
      occupants, increasing the risk of propagule transfer, while temperature increases
      the chance of propagule establishment. Consequently, human activities on these
      islands should be regulated more tightly.

PMID- 18811365
TI  - Annual variability in seed production by woody plants and the masting concept:
      reassessment of principles and relationship to pollination and seed dispersal.
AB  - By analyzing 296 published and unpublished data sets describing annual variation
      in seed output by 144 species of woody plants, this article addresses the
      following questions. Do plant species naturally fall into distinct groups
      corresponding to masting and nonmasting habits? Do plant populations generally
      exhibit significant bimodality in annual seed output? Are there significant
      relationships between annual variability in seed production and pollination and
      seed dispersal modes, as predicted from economy of scale considerations? We
      failed to identify distinct groups of species with contrasting levels of annual
      variability in seed output but did find evidence that most polycarpic woody
      plants seem to adhere to alternating supra-annual schedules consisting of either
      high or low reproduction years. Seed production was weakly more variable among
      wind-pollinated taxa than animal-pollinated ones. Plants dispersed by mutualistic
      frugivores were less variable than those dispersed by either inanimate means or
      animals that predominantly behave as seed predators. We conclude that there are
      no objective reasons to perpetuate the concept of mast fruiting in the ecological
      literature as a shorthand to designate a distinct biological phenomenon.
      Associations between supra-annual variability in seed output and pollination and
      seed dispersal methods suggest the existence of important reproductive correlates
      that demand further investigation.

PMID- 18811366
TI  - A meta-analysis of adaptive deme formation in phytophagous insect populations.
AB  - The adaptive deme formation (ADF) hypothesis predicts that herbivorous insects
      become locally adapted to their host plants over time. Since its inception,
      approximately 17 independent studies have tested ADF, and they are divided in
      support and rejection of the hypothesis. This field of insect evolutionary
      ecology has a contentious history, and the contradictory studies obscure our
      understanding of the general evolutionary importance of adaptive deme formation
      in phytophagous insects. We conducted a meta-analysis in an attempt to clarify
      this issue. Meta-analysis is a statistical method for quantitatively comparing
      and synthesizing the results of different studies in a way that is more objective
      than a traditional literature review. Our analysis indicates that local
      adaptation is an important phenomenon in diverse insect systems. Contrary to
      predictions of the original hypothesis, there was no evidence that insect
      dispersal ability, and ostensibly gene flow, was associated with local adaptive
      differentiation. There was some indication that breeding (parthenogenetic,
      haplodiploid, diplodiploid) and feeding (exophagous, endophagous) modes may
      influence the evolution of locally adapted demes. Our analysis supports the
      theory of adaptive deme formation and provides guidance for future research
      directions.

PMID- 18811367
TI  - Sexual dimorphism in immune defense.
AB  - Sex differences in parasitism are common and may depend on sex differences in
      intensity of sexual competition, immunosuppression, or exposure to parasites. We
      used a large data set on the mass of two immune defense organs in birds (the
      bursa of Fabricius and the spleen) to test for consistent sex differences in
      immune defense. Males had a relative spleen mass that was consistently smaller,
      but more variable, than that of females across species of birds. A sex difference
      in the size of the spleen was not present among juveniles but was large and
      statistically significant among adults. The suppression of spleen mass in adult
      males increased with a measure of intensity of sexual selection: the frequency of
      extra-pair paternity. These findings suggest that sex differences in parasitism
      may arise as a consequence of sex differences in immune function, as mediated by
      sexual selection.

PMID- 18811368
TI  - Antagonistic coevolution over productivity gradients.
AB  - This study addresses the question of how spatial heterogeneity in prey
      productivity and migration act to determine geographic patterns in antagonistic
      coevolution with a predator. We develop and analyze a quantitative coevolutionary
      model for a predator-prey interaction. If the model is modified appropriately,
      the results could broadly apply to multispecies communities and to herbivore
      plant, parasite-host, and parasitoid-host associations. Model populations are
      distributed over a gradient in prey birth rate (as a measure of productivity).
      Each population, in each patch, is made up of a suite of strains. Each strain of
      the predator has a certain ability to successfully attack each strain of the
      prey. We consider scenarios of isolated patches, global migration, and stepping
      stone (i.e., local) migration over a linear string of patches. The most pervasive
      patterns are the following: investments in predator offense and prey defense are
      both maximal in the patches of highest prey productivity; when there are no
      constraints on maximal investment, mean predation evolves to highest levels in
      the most productive patches; similarly, the predator has a greater impact
      (measured as the percentage reduction in prey density) on the prey population in
      high productivity patches as compared with low productivity ones-in spite (even
      after evolution) of prey abundance being highest in the most productive patches;
      and migration has the net effect of shunting relatively offensive and defensive
      strains from productive patches to nonproductive ones, potentially resulting in
      the elimination of otherwise rare, low-investment clones. A modification of the
      model to gene-for-gene type interactions predicts that generalist strains (in
      terms of the range of strains the predator can exploit or the prey can fend off)
      dominate in productive areas of the prey, whereas specialists prevail in marginal
      habitats. Assuming a wide range of productivities over the prey's geographical
      distribution, the greatest strain diversity should be found in habitats of
      intermediate productivity. We discuss the implications of our study for
      adaptation and conservation. Empirical studies are in broad accord with our
      findings.

PMID- 18811369
TI  - Red queen meets Santa Rosalia: arms races and the evolution of host
      specialization in organisms with parasitic lifestyles.
AB  - I argue that nonequilibrium allele frequency dynamics due to coevolution can
      drive the evolution of specialized host races in parasites capable of host choice
      for example, herbivorous insects or parasitoids. The proposed mechanism does not
      require genetic trade-offs in performance on different host species. It is based
      on the premise that the ability of the parasite to overcome the resistance of
      different host species is to a large degree genetically independent-that is,
      controlled by different loci. The intuitive rationale is that the genetic lineage
      of a parasite that evolves host preference becomes more consistently exposed to
      selection for performance on its preferred host. Such a choosy lineage can thus
      coevolve faster in response to evolving host defenses than a generalist lineage
      distributed among several host species. Given genetic variation in host
      preference, an initially generalist parasite population evolves toward
      specialized host races, each choosing one host species. This idea is supported by
      a series of multilocus models of coevolution between a parasite and two host
      species, in which the parasite virulence on each host is affected by a different
      set of loci and an additional locus or two loci control host choice.

PMID- 18811370
TI  - Sex allocation in haplodiploid cyclical parthenogens with density-dependent
      proportion of males.

PMID- 18811371
TI  - Allee effects limit population viability of an annual plant.
AB  - Allee effects may be experienced by plants when populations are too small or
      isolated to receive sufficient pollinator services to replace themselves. This
      article reports experimental data from an annual herb, Clarkia concinna,
      documenting that small patches suffered reproductive failure due to lack of
      effective pollination when critical thresholds of isolation were exceeded. In
      contrast, sufficiently large patches attracted pollinators regardless of their
      degree of isolation. These data accord with data on patch extinctions showing
      that small and isolated patches have a higher extinction rate than do large
      patches and with observations showing chronically low reproductive success in
      such patches prior to extinction. While not conclusively demonstrating that Allee
      effects cause extinction in small and isolated patches, the data are suggestive.
      Although threshold effects have been postulated in several mathematical models of
      population viability, this is the first report of data from natural populations
      that display the occurrence of such thresholds. These results have implications
      for the management of endangered plants, which often are restricted to isolated,
      small populations, as well as suggesting a potential limit to spatial spread in
      plant populations dependent on animal vectors for reproduction.

PMID- 18811372
TI  - Parasite abundance, body size, life histories, and the energetic equivalence
      rule.
AB  - If common processes generate size-abundance relationships among all animals, then
      similar patterns should be observed across groups with different ecologies, such
      as parasites and free-living animals. We studied relationships among body size,
      life-history traits, and population intensity (density in infected hosts) among
      nematodes parasitizing mammals. Parasite size and intensity were negatively
      correlated independently of all other parasite and host factors considered and
      regardless of type of analyses (i.e., nonphylogenetic or phylogenetically based
      statistical analyses, and across or within communities). No other nematode life
      history traits had independent effects on intensity. Slopes of size-intensity
      relationships were consistently shallow, around -0.20 on log-log scale, and thus
      inconsistent with the energetic equivalence rule. Within communities, slopes
      converged toward this global value as size range increased. A summary of
      published values suggests similar convergence toward a global value around -0.75
      among free-living animals. Steeper slopes of size-abundance relationships among
      free-living animals could be related to fundamental differences in ecologies
      between parasites and free-living animals, although such generalizations require
      reexamination of size-abundance relationships among free-living animals with
      regard to confounding factors, in particular by use of phylogenetically based
      statistical methods. In any case, our analyses caution against simple
      generalizations about patterns of animal abundance.

PMID- 18811373
TI  - The evolution of coloniality in birds in relation to food, habitat, predation,
      and life-history traits: a comparative analysis.
AB  - Coloniality in birds has been intensively studied under the cost and benefit
      approach, but no general conclusion can be given concerning its evolutionary
      function. Here, we report on a comparative analysis carried out on 320 species of
      birds using the general method of comparative analysis for discrete variables and
      the contrast method to analyze the evolution of coloniality. Showing a mean of 23
      convergences and 10 reversals, coloniality appears to be a rather labile trait.
      Colonial breeding appears strongly correlated with the absence of feeding
      territory, the aquatic habitat, and nest exposure to predators but was not
      correlated with changes in life-history traits (body mass and clutch size). The
      correlation of coloniality with the aquatic habitat is in fact explained by a
      strong correlation with the marine habitat. Unexpectedly, we found that the
      evolution toward a marine habitat in birds was contingent on coloniality and that
      coloniality evolved before the passage to a marine life. These results-along with
      the lack of transitions from the nonmarine to marine habitat in solitary species
      and the precedence of the loss of feeding territoriality on the passage to a
      marine life-contradict most of the hypotheses classically accepted to explain
      coloniality and suggest that we use a different framework to study this
      evolutionary enigma.

PMID- 18811374
TI  - Geographic variation in competitive ability in Drosophila melanogaster.
AB  - The aim of this study was to examine the latitudinal variation in preadult
      competitive ability of Drosophila melanogaster. Two pairs of populations from
      Queensland and Tasmania, Australia, were examined. Queensland flies are
      genetically smaller and develop more slowly than the Tasmanian flies. Survival
      and body size of flies raised at different temperatures and densities were
      compared when larvae were challenged with a common competitor. No latitudinal
      variation in larval survival was detected. Body size (measured as wing length)
      decreased with increasing temperature and larval density. Flies from the
      Tasmanian populations were more sensitive to the effects of temperature and
      density and to the joint effect of increased temperature and density. This could
      explain the evolution of greater growth efficiency and larger body size at lower
      temperatures.

PMID- 18811375
TI  - Evolution of a mate recognition system after hybridization between two Drosophila
      species.
AB  - I investigated the genetic relationship between male and female components of the
      mate recognition system and how this relationship influenced the subsequent
      evolution of the two traits, in a series of replicate populations of
      interspecific hybrids. Thirty populations of hybrids between Drosophila serrata
      and Drosophila birchii were established and maintained for 24 generations. At the
      fifth generation after hybridization, the mating success of hybrid individuals
      with the D. serrata parent was determined. The genetic correlation between male
      and female components of the mate recognition system, as a consequence of
      pleiotropy or tight physical linkage, was found to be significant but low (r =
      0.388). This result suggested that pleiotropy may play only a minor role in the
      evolution of mate recognition in this system. At the twenty-fourth generation
      after hybridization, the mating success of the hybrids was again determined. The
      evolution of male and female components was investigated by analyzing the
      direction of evolution of each hybrid line with respect to its initial position
      in relation to the genetic regression. Male and female components appeared to
      converge on a single equilibrium point, rather than evolving along trajectories
      with slope equal to the genetic regression, toward a line of equilibria.

PMID- 18811376
TI  - Social and genetic structure of paper wasp cofoundress associations: tests of
      reproductive skew models.
AB  - Recent models postulate that the members of a social group assess their
      ecological and social environments and agree a "social contract" of reproductive
      partitioning (skew). We tested social contracts theory by using DNA
      microsatellites to measure skew in 24 cofoundress associations of paper wasps,
      Polistes bellicosus. In contrast to theoretical predictions, there was little
      variation in cofoundress relatedness, and relatedness either did not predict skew
      or was negatively correlated with it; the dominant/subordinate size ratio,
      assumed to reflect relative fighting ability, did not predict skew; and high skew
      was associated with decreased aggression by the rank 2 subordinate toward the
      dominant. High skew was associated with increased group size. A difficulty with
      measuring skew in real systems is the frequent changes in group composition that
      commonly occur in social animals. In P. bellicosus, 61% of egg layers and an
      unknown number of non-egg layers were absent by the time nests were collected.
      The social contracts models provide an attractive general framework linking
      genetics, ecology, and behavior, but there have been few direct tests of their
      predictions. We question assumptions underlying the models and suggest directions
      for future research.

PMID- 18811377
TI  - Natural selection and the sex ratio: Fisher's sources.

PMID- 18811378
TI  - Do female three-spined sticklebacks copy the mate choice of others?

PMID- 18811379
TI  - Running from trouble: long-distance dispersal and the competitive coexistence of
      inferior species.

PMID- 18811380
TI  - Persistence and area effects in a stochastic tritrophic model.

PMID- 18811383
TI  - Trade-off between virulence and vertical transmission and the maintenance of a
      virulent plant pathogen.
AB  - The continuum hypothesis predicts that parasites should evolve reduced virulence
      if they have higher opportunity for vertical transmission. However, when there is
      a trade-off between virulence and vertical transmission, selection may favor
      horizontal transmission and higher virulence. Atkinsonella hypoxylon is a fungal
      pathogen that reduces Danthonia fitness by 50% or more when it completely
      castrates hosts' chasmogamous inflorescences, despite the high opportunity for
      vertical transmission through cleistogamous seeds. Sporadically, infected hosts
      with partially castrated inflorescences (which have higher fecundity than
      completely castrated hosts) are observed in natural populations. Why are
      partially castrated plants rare if selection favors reduced virulence? We
      investigated whether there was genetic diversity for virulence among A. hypoxylon
      genotypes and the relationship between virulence and vertical transmission. We
      found that the fungal genotype significantly affects the occurrence of partial
      castration in Danthonia compressa. The proportion of seedlings that were
      vertically infected by their maternal plant was lower for partially castrated
      than for completely castrated plants. Our results demonstrate a trade-off between
      virulence and vertical transmission, explaining the maintenance of more virulent,
      completely castrating fungal genotypes in natural populations, and suggest that
      vertical transmission in plants is more complex than what is considered in
      current models.

PMID- 18811384
TI  - Detecting shifts in diversification rates without fossils.
AB  - Studies of shifts in diversification rates and adaptive radiations are difficult
      when there are no fossils because past events cannot be inferred. The phylogenies
      of recent species, however, allow one to infer the patterns of past
      diversifications. I present a new method for estimating the diversification rate
      of a lineage, provided that a phylogeny of recent species, constructed, for
      instance, with molecular data, is available. This method was inspired by survival
      models and takes into account species that are not included in detailed
      phylogenetic data, provided that approximate dates of origin of these species are
      known. Likelihood ratio tests and Akaike Information Criterion make it possible
      to test for differences in diversification among lineages or groups of lineages
      and, thus, to evaluate adaptive radiation hypotheses. The present modeling
      approach can easily be extended to include temporal variations in diversification
      rates. A simulation study showed that the method is statistically consistent,
      avoiding Type I and Type II errors, and that it is robust to periodic or random
      fluctuations in the speciation rate. An example is presented with a composite
      phylogeny of primates.

PMID- 18811385
TI  - Natural selection on two seed-size traits in the common morning glory Ipomoea
      purpurea (Convolvulaceae): patterns and evolutionary consequences.
AB  - Plants may express two separate seed-size characters during their lifetimes: the
      size of the seeds from which they germinate (initial seed size) and the mean size
      of seed they produce as adults (maternal seed size). Many empirical studies
      indicate that selection often favors a larger initial seed size. In contrast,
      patterns of natural selection on maternal seed size have not been measured,
      although theory often predicts stabilizing selection. Here, I report on a field
      study of the common morning glory Ipomoea purpurea, which provided measurements
      of natural selection on both initial and maternal seed size. For initial seed
      size, selection favored larger seeds, but a greenhouse study indicated no genetic
      variation for this trait. For maternal seed size, there was no evidence of either
      directional or stabilizing selection, but there was significant additive genetic
      variation. The genetic correlation between the number and size of seeds was not
      significant, indicating no trade-off between these traits, but a negative genetic
      correlation was found between maternal seed size and the probability of surviving
      to reproduce. The absence of the predicted pattern of stabilizing selection on
      maternal seed size in the study population highlights the need for more empirical
      work on the evolution of seed size.

PMID- 18811386
TI  - Why trees migrate so fast: confronting theory with dispersal biology and the
      paleorecord.
AB  - Reid's paradox describes the fact that classical models cannot account for the
      rapid (10(2)-10(3) m yr-1) spread of trees at the end of the Pleistocene. I use
      field estimates of seed dispersal with an integrodifference equation and
      simulation models of population growth to show that dispersal data are compatible
      with rapid spread. Dispersal estimates lay to rest the possibility that rapid
      spread occurred by diffusion. The integrodifference model predicts that, if the
      seed shadow has a long 'fat' tail, then rapid spread is possible, despite short
      average dispersal distances. It further predicts that velocity is more sensitive
      to life history than is classical diffusion. Application of such models is
      frustrated because the tail of the seed shadow cannot be fitted to data. However,
      the data can be used to test a 'long-distance' hypothesis against alternative
      ('local') models of dispersal using Akaike's Information Criterion and likelihood
      ratio tests. Tests show that data are consistent with >10% of seed dispersed as a
      long (10(2) m) fat-tailed kernel. Models based on such kernels predict spread as
      rapid as that inferred from the pollen record. If fat-tailed dispersal explains
      these rapid rates, then it is surprising not to see large differences in
      velocities among taxa with contrasting life histories. The inference of rapid
      spread, together with lack of obvious life-history effects, suggests velocities
      may have not reached their potentials, being stalled by rates of climate change,
      geography, or both.

PMID- 18811387
TI  - Evolution of mirror images by sexually asymmetric mating behavior in
      hermaphroditic snails.
AB  - Directionally asymmetric animals generally exhibit no variation in handedness of
      whole-body architecture. In contrast, reversed chirality in both coil and entire
      anatomy has frequently evolved in snails. We demonstrate a nonrandom pattern and
      deterministic process of chiral evolution, as predicted by the following
      hypothesis. Bimodal shell shapes are associated with discrete mating behaviors in
      hermaphroditic pulmonates. Flat-shelled species mate reciprocally, face-to-face.
      This sexual symmetry prevents interchiral mating because genitalia exposed by a
      sinistral on its left side cannot be joined with those exposed by a dextral on
      its right. Thus, selection against the chiral minority, resulting from mating
      disadvantage, stabilizes chiral monomorphism. Tall-shelled species mate
      nonreciprocally: the 'male' copulates by mounting the 'female's' shell, mutually
      aligned in the same direction. This sexual asymmetry permits interchiral
      copulation with small behavioral adjustments. Therefore, the positive frequency
      dependent selection is relaxed, and reversal alleles persist longer in
      populations of tall-shelled species. We verified both the assumption and the
      prediction of this hypothesis: significantly lower interchiral mating success in
      a low-spired species and higher chiral evolution rate in high-spired taxa. Sexual
      asymmetry is the key to understanding the accelerated chiral evolution in high
      spired pulmonates.

PMID- 18811388
TI  - Predator-mediated plasticity in morphology, life history, and behavior of
      Daphnia: the uncoupling of responses.
AB  - We studied the way 12 traits responded to fish kairomones in a set of 16 Daphnia
      magna clones derived from four different habitats-two where daphnids co-occur
      with fish and two without fish. These clones differed widely in their response to
      predator kairomones, with none of the clones showing a significant response in
      all traits and all clones showing a response for at least one trait. Most of the
      clones showed a significant response in one to four traits, with no evidence for
      an association between different traits. Clones from fish habitats were slightly
      more responsive to the presence of fish kairomones than clones from fishless
      locations. We conclude that most clones show an induced response to the presence
      of their predators (fish) but that there is a large genetic variability with
      respect to the traits for which clones show a response. Our results indicate that
      the major distinction is not between inducible and noninducible genotypes but
      rather that the genotypes differ in the combination of traits for which they show
      inducible responses.

PMID- 18811389
TI  - Context-dependent behavior and the benefits of communal nesting.
AB  - We present a model for the behavior of communally nesting insects. Females may
      forage for food to provision offspring or may remain in the nest, with the option
      of eating and replacing nest mates' eggs. Orphaned brood are at risk of
      predation. The optimal behavior of solitary females is determined using
      stochastic dynamic programming; static and dynamic evolutionarily stable
      strategies (ESSs) are then calculated for colonies of various sizes. A solitary
      female should forage if her brood is smaller than a time-dependent threshold.
      Females in small colonies should forage. In colonies above some threshold size,
      the static ESS is for one female to forage and the rest to cheat. The dynamic ESS
      in large colonies is for no females to forage until some time close to the end of
      the foraging season and for all females to forage thereafter. Mixed dynamic ESSs,
      with some foragers and some cheats, may arise if individuals differ in their
      chances of surviving a foraging interval or if females with new offspring vary
      their guarding behavior, depending on the numbers of cheats and new cells in the
      nest. We discuss these predictions in the light of published observations and
      preliminary data on the halictine bee Lasioglossum (Chilalictus) hemichalceum.

PMID- 18811390
TI  - On the origin and rarity of interspecific nest parasitism in birds.
AB  - Interspecific nest parasitism is surprisingly rare in birds given the potential
      advantages for the parasite of exploiting the parental care of other species. One
      possibility is that chicks will not thrive with the parental care and food of
      heterospecifics. I simulated parasitism in nonparasitic congeners by switching
      eggs between nests of three species of titmice (great tit Parus major, blue tit
      Parus caeruleus, and coal tit Parus ater). The experiment showed that
      compatibility of parental care was not a constraint preventing parasitism. I also
      used the model system to compare fitness consequences of inter- and intraspecific
      nest parasitism, addressing the problem of which form is ancestral. Fledging
      success (body mass, survival) was higher when an egg was added to the nest of a
      smaller species than to the nest of a conspecific and also higher when the
      parasitic chick hatched early rather than late relative to host chicks. This
      suggests that interspecific nest parasitism may not require a stage of
      intraspecific nest parasitism before evolving but may start from a larger species
      directly exploiting the parental care of a smaller species or a species with
      shorter incubation period directly exploiting a species with longer incubation
      period.

PMID- 18811391
TI  - Effects of time limitation and egg limitation on lifetime reproductive success of
      a parasitoid in the field.
AB  - We used field observations of freely foraging Aphytis aonidiae parasitoids in
      conjunction with results of laboratory studies of A. aonidiae and other Aphytis
      species to simulate lifetime patterns of behavior and reproduction. Field
      observations provided estimates of encounter rates with three classes of hosts,
      the mortality rate from predation on adult parasitoids, and host-handling times
      for oviposition and host feeding by adult wasps. A series of physiological
      parameters, including the egg maturation rate and the value of host-feeding
      meals, were estimated from previously published studies. Plasticity in parasitoid
      behavior was incorporated in two ways. For one set of simulations we used a
      behavioral rule derived empirically from observations of parasitoids made in the
      field, and for another we used a dynamic state-variable model to generate a set
      of behavioral rules that maximize lifetime reproductive success. As was expected,
      the empirically derived rule led to better matches with field observations than
      did simulations using the output of the dynamic model. Projections of lifetime
      reproductive success in the field ranged between three and 37 eggs within the 95%
      confidence intervals of the mortality rate and host encounter rate and depending
      on which behavioral rule was used. Lifetime reproductive success from the
      simulation with central estimates of the mortality and host encounter rates that
      incorporated the empirical rule was 6.25 eggs. Using the empirical versus the
      theoretical rule in the simulations led to a 10%-30% decline in projections of
      lifetime reproductive success, depending on mortality and host encounter rates.
      Regardless of the behavioral rule, the simulations underscored the observation
      that the host encounter rate was greater than the egg maturation rate. The
      overall oviposition rate was sufficiently high to lead to daily episodes of
      temporary egg limitation during which parasitoids must mature an egg before being
      able to oviposit.

PMID- 18811392
TI  - Polyspermy, egg size, and the fertilization kinetics of free-spawning marine
      invertebrates.

PMID- 18811393
TI  - Allee effects in metapopulation dynamics.

PMID- 18811394
TI  - Extinction in multispecies and spatially explicit models of habitat destruction.

PMID- 18811395
TI  - Austral migrants and the evolution of migration in new world birds: diet,
      habitat, and migration revisited.

PMID- 18811396
TI  - Sewall Wright Award 1997: Douglas Joel Futuyma.

PMID- 18811397
TI  - The ghost of genetic diversity past: historical DNA analysis of the greater
      prairie chicken.
AB  - Most, if not all, of the "classic," often-cited examples illustrating the genetic
      effects of a population bottleneck are open to alternative explanations due to
      the lack of adequate control populations, that is, low levels of genetic
      variability are often assumed to be the result of a past population bottleneck
      without having any prebottleneck measures. Here we provide the first clear case
      history where both prebottleneck and postbottleneck measures of genetic
      variability have been collected from a natural system. Analysis of DNA from
      museum specimens of the greater prairie chicken Tympanuchus cupido from central
      Illinois revealed the loss of specific alleles (known to have been present
      earlier in this century) following a demographic contraction. Lost alleles
      included common ones present in all other populations sampled and others unique
      to the Illinois population.

PMID- 18811398
TI  - The physiology of life-history trade-offs: experimental analysis of a hormonally
      induced life-history trade-off in Gryllus assimilis.
AB  - Adult Gryllus assimilis given an analog of juvenile hormone exhibited reduced
      flight muscles and enlarged ovaries similar to those found in naturally occurring
      flightless individuals of species that are polymorphic for dispersal capability.
      Control and hormone-treated (flightless) G. assimilis did not differ in the
      amount of food consumed or assimilated on any of three diets that differed in
      nutrient quantity. Thus, enhanced ovarian growth of flightless individuals
      resulted from increased allocation of internal nutrients to reproduction (i.e., a
      trade-off) rather than from increased acquisition of nutrients. Compared with
      flight-capable controls, flightless G. assimilis also had reduced whole-organism
      respiration, reduced respiration of flight muscles, and reduced lipid and
      triglyceride (flight fuel) reserves. These differences are remarkably similar to
      those between naturally occurring flightless and flight-capable morphs of other
      Gryllus species. Results collectively suggest that the increased allocation of
      nutrients to ovarian growth in flightless G. assimilis and other Gryllus species
      results from reduced energetic costs of flight muscle maintenance and/or the
      biosynthesis or acquisition of lipids. Reduction in these energetic costs appears
      to be an important driving force in the evolution of flightlessness in insects.
      Respiratory metabolism associated with flight capability utilizes an increasing
      proportion of the energy budget of crickets as the quantity of nutrients in the
      diet is decreased. This leads to a magnification of greater ovarian growth of
      flightless versus flight-capable individuals on nutrient-poor diets.

PMID- 18811399
TI  - Evolutionary theories of aging: confirmation of a fundamental prediction, with
      implications for the genetic basis and evolution of life span.
AB  - Evolutionary considerations predict that rate of aging should vary in direct
      relation to the mortality rate of presenescent young adults (extrinsic mortality
      rate) independently of differences in physiology, such as rate of metabolism.
      This prediction emerges from theory irrespective of the particular genetic
      mechanisms responsible for variation in aging. Yet this critical relationship has
      not been confirmed in comparative studies of natural populations. In the present
      analysis, rate of aging is estimated by the rate of increase in mortality rate
      (mx) with age (x). Comparisons between natural and captive populations of birds
      suggest that the Weibull model (mx = m0 + alphaxbeta) provides a better
      description of aging than the Gompertz model (mx = m0esigmax). Rate of aging is
      quantified by the parameter omega (dimension: 1/time), which is calculated from
      the Weibull parameters alpha and beta (omega = alpha1/(beta+1)). In this
      analysis, rate of aging in birds and mammals is directly related to extrinsic
      mortality (estimated by the initial mortality rate, m0) independently of
      taxonomic group and of variation in body size and, by implication, metabolic
      rate. When time is expressed in years, rate of senescence is related to initial
      mortality rate by omega = 0.294m0(0.367). This result implies that natural
      selection in response to variation among taxa in m0 has resulted in the
      evolutionary modification of factors that influence the rate of aging in natural
      populations. The potential strength of selection on factors that could further
      reduce rate of aging is indicated by the proportion of deaths due to aging
      related causes. Although species with low initial mortality rates also exhibit
      reduced rates of increase in mortality rate with age (i.e., delayed senescence),
      the relatively high proportion of aging-related deaths in such species suggests
      that further evolutionary responses leading to long life are severely
      constrained. This argues against mutation accumulation and antagonistic
      pleiotropy as genetic mechanisms underlying senescence and suggests, instead,
      that rate of aging represents a balance between wear and tear, on the one hand,
      and genetically controlled mechanisms of prevention and repair, on the other.
      Evidently, remedies for extreme physiological deterioration in old age either are
      not within the range of genetic variation or are too costly to be favored by
      selection.

PMID- 18811400
TI  - Efficacy and honesty in communication between relatives.
AB  - The evolution of honest communication has recently become the focus of intense
      theoretical attention. However, strategic models dealing with honesty have
      largely ignored the implications of noise and perceptual error for signal
      evolution (just as models dealing with signal detection in the presence of noise
      ignore strategic issues). Here, I analyze an extended version of Maynard Smith's
      strategic model of signaling of need between relatives, the Philip Sidney game,
      that incorporates the possibility of perceptual error. I show that even in the
      presence of noise, there exists over a wide range of parameter values a unique,
      continuously stable signaling equilibrium, at which the signaler employs a costly
      display when needy but refrains from doing so when healthy. For a subset of this
      range, there also exists a second, lower cost signaling equilibrium that is not
      continuously stable. At the former equilibrium, predicted signal cost is
      inversely related to the coefficient of relatedness (r) between signaler and
      receiver. Cost is not, however, predicted to drop to zero even when r = 1 and
      there is no conflict of interest between the two (as is the case in errofree
      models), because it serves to enhance the efficacy of communication as well as to
      discourage deceit. Equilibrium signal cost is inversely related to the
      probability that the signaler is needy, and tends to increase with the level of
      noise. If noise becomes too great (i.e., if a detectable signal is too costly to
      produce), signaling is no longer stable; surprisingly, it is also unstable if the
      level of noise is too low (i.e., if a detectable signal is too cheap to produce).

PMID- 18811401
TI  - The maintenance of nucleocytoplasmic polymorphism in a metapopulation: the case
      of gynodioecy.
AB  - In gynodioecious species, gender is generally determined by epistatic
      interactions between cytoplasmic and nuclear loci. However, theoretical studies
      suggest that, for a joint polymorphism at both cytoplasmic and nuclear loci to be
      maintained in a panmictic population, selection must act differently on the
      various genotypes that determine the same gender. Here we show that, in a
      metapopulation with local extinction and restricted gene flow, nucleocytoplasmic
      polymorphism can be maintained without these differences. We use deterministic
      simulations. We assume that gene flow occurred only at recolonization. Founder
      effects create genetic variance between populations in the metapopulation, and
      local population growth is faster when the local frequency of females is high.
      Group selection phenomena are involved in the maintenance of the joint
      polymorphism in the metapopulation. The frequency of females in the
      metapopulation at equilibrium is higher than in a panmictic population with the
      same genetic system. However, these conclusions hold only if nuclear alleles
      restoring male fertility are dominant.

PMID- 18811402
TI  - Competition in a group of equal foragers.
AB  - Using techniques from renewal process theory, we build a stochastic model for
      gain accumulation in a group of equal competitors foraging in a patchy
      environment. The model for gain of the individuals is based on the waiting times
      between subsequent prey encounters by the group. These waiting times depend on
      the number of foragers in the group. A single parameter of this dependency
      encompasses a variety of foraging scenarios, from co-operation to scramble. With
      constant patch size, correlations between gains of any pair of foragers are
      negative. This dependency is most intense in small groups. Increased variation in
      patch size makes correlations in gains between group members positive
      irrespective of the group size. For a solitary forager, variance in gain
      approaches zero with increasing time in the patch. For an individual member in a
      group, variance grows monotonically. Thus, depending on the patch departure rule
      controlling the time to be spent in the patch, solitary foragers may have a
      smaller variance in gain than members in a group. As solitary foragers also
      potentially harvest all prey in the patch, it is hard to believe that grouping
      behavior would evolve solely on the basis of foraging.

PMID- 18811403
TI  - Statistical analyses of developmental sequences: the craniofacial region in
      marsupial and placental mammals.
AB  - Heterochrony is most often thought to involve changes in the rate of development
      or maturation (rate changes). However, heterochrony can also involve changes in
      the timing of specific developmental events relative to other events (sequence
      changes). Sequence changes have received much less attention than have changes in
      developmental rates, in part because few methods exist for comparing
      developmental sequences. Here, we present two methods to statistically evaluate
      developmental sequence changes. First, Kendall's coefficient of concordance (W)
      is used to quantify overall similarity of developmental sequences in two or more
      groups of organisms, and second, ANOVA is used to identify the individual events
      that differ most in their relative developmental timing. Computer simulation is
      used to control for the nonindependence of species. We examine the sequence of
      developmental events in the craniofacial region of marsupial and placental
      mammals. We conclude that the most important differences in development in the
      two clades relate to the relative sequence of development of the central nervous
      system and somatic elements of the craniofacial region. The rationale behind the
      methods and their limitations are discussed, and the results from this study are
      compared with a previous analysis.

PMID- 18811404
TI  - The evolution of temporal patterns of selfishness, altruism, and group cohesion.
AB  - In intrademic selection models, individuals interact in groups, and this
      interaction phase is usually treated as a point in time. It is likely, however,
      that interactions take place over some time period. If selfishness is treated as
      a quantitative trait and this time period is explicitly considered, how does the
      evolutionarily stable strategy (ESS) level of selfishness or altruism change
      through time? Our main result is that, under biologically reasonable conditions,
      the ESS level of selfishness is expected to increase. Two of the assumptions
      behind this result are that there is a finite time horizon on the life of the
      group and that reproduction occurs continuously throughout the time period in
      question. If there is no time horizon or if all reproductive output is
      concentrated at the end of the time period, the ESS level of selfishness is
      constant. Our main result suggests that care must be taken when interpreting
      empirical data that is collected at different times and that altruism will often
      be most pronounced when groups first form. The model also demonstrates that, when
      individuals interact repeatedly over time, the evolution of altruism can be
      promoted through a mechanism other than reciprocity.

PMID- 18811405
TI  - High competition with low similarity and low competition with high similarity:
      exploitative and apparent competition in consumer-resource systems.
AB  - This article investigates the relationship between the similarity of resource
      capture abilities and the amount of competition between two consumer species that
      exploit common resources. Most of the analysis is based on a consumer-resource
      model introduced by Robert MacArthur. Contrary to many statements in the
      literature and in textbooks, measures of competition may decrease as similarity
      increases and may be greatest when similarity of the two species' sets of
      resource capture rates is very low. High competition with low similarity may
      occur whether competition is measured by a competition coefficient near
      equilibrium or is measured by the proportional increase in a species' population
      density when its competitor is removed. However, these two measures may differ
      considerably and may change in opposite directions with a given change in
      similarity. The general conditions required for such counterintuitive
      relationships between similarity and competition are that the consumer species
      have relatively low resource requirements for successful reproduction and that
      the resources be self-reproducing. These same conditions also frequently lead to
      exclusion of one or more resources via apparent competition, and this is always
      true of MacArthur's model. A variety of other models of competition are analyzed,
      and circumstances most likely to produce large competitive effects with little
      overlap are identified.

PMID- 18811406
TI  - Premating isolation is determined by larval rearing substrates in cactophilic
      Drosophila mojavensis. IV. Correlated responses in behavioral isolation to
      artificial selection on a life-history trait.
AB  - Studies of behavioral isolation among geographically isolated populations of
      Drosophila mojavensis have provided an understanding of incipient speciation
      wherein phylogeny and ecology play a prominent role. Populations of D. mojavensis
      in mainland Mexico and southern Arizona exhibit low but significant premating
      isolation from Baja California populations in laboratory mate choice tests. These
      same populations have undergone considerable life-history evolution in response
      to use of different host plants, suggesting that behavioral isolation between
      populations is a pleiotropic consequence of adaptation to different environments,
      or Mayr's geographic speciation hypothesis. This hypothesis was tested using
      bidirectional artificial selection on egg-to-adult development time in replicate
      lines of a mainland and Baja population cultured on two host cacti for 13
      generations. Response to selection was greatest in the slow lines cultured on one
      host, yet there was uneven response in some lines due to variation in cactus
      tissue quality. Realized heritabilities for development time ranged from 0.04 to
      0.16, which is consistent with previous estimates from half-sib/full-sib analyses
      of genetic variation. In most lines that responded to selection, premating
      isolation decreased to near zero. Correlated responses in behavioral isolation
      suggest that adaptation to contrasting environments can cause secondary responses
      in mate recognition systems that can influence the formation of new species.

PMID- 18811407
TI  - Maintenance of genetic polymorphism: spatial selection and self-fertilization.

PMID- 18811408
TI  - On the use of path analysis and related procedures for the investigation of
      ecological problems.

PMID- 18811409
TI  - Path modeling methods and ecological interactions: a response to Grace and
      Pugesek.

PMID- 18811410
TI  - A commentary on prime numbers and life cycles of periodical cicadas.

PMID- 18811411
TI  - Using spatially explicit models to characterize foraging performance in
      heterogeneous landscapes.
AB  - The success of most foragers is constrained by limits to their sensory
      perception, memory, and locomotion. However, a general and quantitative
      understanding of how these constraints affect foraging benefits, and the trade
      offs they imply for foraging strategies, is difficult to achieve. This article
      develops foraging performance statistics to assess constraints and define trade
      offs for foragers using biased random walk behaviors, a widespread class of
      foraging strategies that includes area-restricted searches, kineses, and taxes.
      The statistics are expected payoff and expected travel time and assess two
      components of foraging performance: how effectively foragers distinguish between
      resource-poor and resource-rich parts of their environments and how quickly
      foragers in poor parts of the environment locate resource concentrations. These
      statistics provide a link between mechanistic models of individuals' movement and
      functional responses, population-level models of forager distributions in space
      and time, and foraging theory predictions of optimal forager distributions and
      criteria for abandoning resource patches. Application of the analysis to area
      restricted search in coccinellid beetles suggests that the most essential aspect
      of these predators's foraging strategy is the "turning threshold," the prey
      density at which ladybirds switch from slow to rapid turning. This threshold
      effectively determines whether a forager exploits or abandons a resource
      concentration. Foraging is most effective when the threshold is tuned to match
      physiological or energetic requirements. These performance statistics also help
      anticipate and interpret the dynamics of complex spatially and temporally varying
      forager-resource systems.

PMID- 18811412
TI  - Resolving discrepancies between deterministic population models and individual
      based simulations.
AB  - This work ties together two distinct modeling frameworks for population dynamics:
      an individual-based simulation and a set of coupled integrodifferential equations
      involving population densities. The simulation model represents an idealized
      predator-prey system formulated at the scale of discrete individuals, explicitly
      incorporating their mutual interactions, whereas the population-level framework
      is a generalized version of reaction-diffusion models that incorporate population
      densities coupled to one another by interaction rates. Here I use various
      combinations of long-range dispersal for both the offspring and adult stages of
      both prey and predator species, providing a broad range of spatial and temporal
      dynamics, to compare and contrast the two model frameworks. Taking the individual
      based modeling results as given, two examinations of the reaction-dispersal model
      are made: linear stability analysis of the deterministic equations and direct
      numerical solution of the model equations. I also modify the numerical solution
      in two ways to account for the stochastic nature of individual-based processes,
      which include independent, local perturbations in population density and a
      minimum population density within integration cells, below which the population
      is set to zero. These modifications introduce new parameters into the population
      level model, which I adjust to reproduce the individual-based model results. The
      individual-based model is then modified to minimize the effects of stochasticity,
      producing a match of the predictions from the numerical integration of the
      population-level model without stochasticity.

PMID- 18811413
TI  - Populational heritability: empirical studies of evolution in metapopulations.
AB  - Using demes from experimental metapopulations of the flour beetle, Tribolium
      castaneum, we investigated phase 3 of Wright's shifting balance process. Using
      parent demes of high, intermediate, and low mean fitness, we experimentally
      modeled migration of varying amounts from demes of high mean fitness into demes
      of lower mean fitness (like phase 3) as well as the reciprocal (the opposite of
      phase 3). In natural populations, some migration among demes occurs independently
      of deme fitness. In this case, demes of high mean fitness are likely to receive
      migrants from demes of lower mean fitness; these effects might limit the
      effectiveness of phase 3 but have not been studied experimentally. We estimated
      the populational heritability of mean fitness by the regression of offspring deme
      means on the weighted parental means and found moderate levels of demic
      heritability one (0.641-0.690) and two (0.518-0.552) generations after migration.
      We discuss our findings in relation to the role of interdemic migration in
      "adaptive peak shifts" in metapopulations and the controversies over group
      selection and the units of inheritance.

PMID- 18811414
TI  - A genetic polymorphism maintained by natural selection in a temporally varying
      environment.
AB  - Environments that are crowded with larvae of the fruit fly, Drosophila
      melanogaster, exhibit a temporal deterioration in quality as waste products
      accumulate and food is depleted. We show that natural selection in these
      environments can maintain a genetic polymorphism with one group of genotypes
      specializing on the early part of the environment and a second group specializing
      on the late part. These specializations involve trade-offs in fitness components.
      The early types emerge first from crowded cultures and have high larval feeding
      rates, which are positively correlated with competitive ability but exhibit lower
      absolute viability than the late phenotype, especially in food contaminated with
      the nitrogenous waste product, ammonia. The late emerging types have reduced
      feeding rates but higher absolute survival under conditions of severe crowding
      and high levels of ammonia. Organisms that experience temporal variation within a
      single generation are not uncommon, and this model system provides some of the
      first insights into the evolutionary forces at work in these environments.

PMID- 18811415
TI  - Birds' tails as signaling devices: markings, shape, length, and feather quality.
AB  - While exaggerated length and ornamental shapes are confirmed sexually selected
      tail traits in birds, the signal function of tail markings has received less
      study. Signal roles for tail markings as amplifiers of length, shape, and feather
      quality are discussed, and the role of tail markings as feather-quality handicaps
      is proposed: absence of melanin increases damage and abrasion. Predicted
      correlations of tail markings with other tail traits are derived for these signal
      roles. A comparative study of the relationships between these tail traits in an
      entire avifauna, the western Palearctic, tested the predictions. Tail displays
      were present in nearly 80% of species, associated with greater long-tailedness,
      but not all displayed tails had markings or ornamental shape. The incidence of
      marks across tail shapes and the combinations of marks indicate that tail
      markings act as handicaps or amplifying handicaps of tail feather quality. Tail
      elongation and ornamental shapes could act as additional handicaps of feather
      quality-that is, they could be multipurpose signals. Incorporation of revealing
      indicators such as feather damage and associated handicap and/or amplifying
      traits may allow a reduction in the cost of signaling while maintaining signal
      reliability and, hence, influence sexual selection in complex signaling systems.

PMID- 18811416
TI  - Bilateral symmetry and sexual selection: a meta-analysis.
AB  - A considerable body of primary research has accumulated over the last 10 yr
      testing the relationship between developmental instability in the form of
      fluctuating asymmetry and performance of individuals in mating success itself or
      sexual attractiveness. This research comprises 146 samples from 65 studies of 42
      species of four major taxa. We present the results of a meta-analysis of these
      studies, which demonstrates that there is indeed an overall significant, moderate
      negative relationship: for studies, the overall mean Pearson's r or effect size =
      -.42, P <.0005; for species, the overall mean r = -.34, .01 < P < .025. Based on
      calculated fail-safe numbers, the effect-size estimates are highly robust against
      any publication or reporting bias that may exist. There is considerable evidence
      that the magnitude of the negative correlation between fluctuating asymmetry and
      success related to sexual selection is greater for males than for females, when a
      secondary sexual trait rather than an ordinary trait is studied, with
      experimentation compared with observation, and for traits not involved with
      mobility compared with traits affecting mobility. There is also limited evidence
      that higher taxa may differ in effect size and that intensity of sexual selection
      negatively correlates with effect size.

PMID- 18811417
TI  - Why do all host species not show defense against avian brood parasitism:
      evolutionary lag or equilibrium?
AB  - Avian brood parasitism reduces the reproductive success of hosts and is therefore
      expected to select for host defenses against parasitism, such as an ability to
      reject parasitic eggs. Field studies have shown that some hosts recognize and
      reject parasitism, whereas others do not, and the degree of the defense varies
      from population to population. One long-standing debate concentrates on the
      differences in the distribution of host defenses observed in hosts parasitized by
      the brown-headed cowbird and the common cuckoo. The cowbird's hosts show either
      few or nearly perfect defenses, whereas the cuckoo's hosts have defenses varying
      from none to complete, with most falling in between the two extremes. To explore
      the mechanisms underlying this pattern, I constructed a mathematical model in
      which host defense is assumed to be genetically determined and analyzed how the
      host defense is established under parasitic pressure. The model shows that
      differences in the defense-level distribution can be attributed to the difference
      in the parasite's breeding strategy, generalized or specialized: hosts
      parasitized by generalists show perfect, none, or intermediate levels of the
      defense depending on the host abundances, whereas hosts parasitized by
      specialists always exhibit either none or intermediate levels of the defense if
      the parasite lacks counter defenses such as egg mimicry. This result provides a
      testable explanation for the existence of accepter species of the brown-headed
      cowbird, which might reconcile the previously conflicting hypotheses.

PMID- 18811418
TI  - 1996 Sewall Wright Award: Robert T. Paine.

PMID- 18811419
TI  - Wherefore and whither the naturalist?

PMID- 18811420
TI  - Genetic maternity and paternity in a local population of armadillos assessed by
      microsatellite DNA markers and field data.
AB  - Genetic data from polymorphic microsatellite loci were employed to estimate
      paternity and maternity in a local population of nine-banded armadillos (Dasypus
      novemcinctus) in northern Florida. The parentage assessments took advantage of
      maximum likelihood procedures developed expressly for situations when individuals
      of neither gender can be excluded a priori as candidate parents. The molecular
      data for 290 individuals, interpreted alone and in conjunction with detailed
      biological and spatial information for the population, demonstrate high exclusion
      probabilities and reasonably strong likelihoods of genetic parentage assignment
      in many cases; low mean probabilities of successful reproductive contribution to
      the local population by individual armadillo adults in a given year; and
      statistically significant microspatial associations of parents and their
      offspring. Results suggest that molecular assays of highly polymorphic genetic
      systems can add considerable power to assessments of biological parentage in
      natural populations even when neither parent is otherwise known.

PMID- 18811421
TI  - Costs of resistance to natural enemies in field populations of the annual plant
      Arabidopsis thaliana.
AB  - The annual plant Arabidopsis thaliana is widely used as a model system in
      molecular genetics, but little is known about populations in the field. In this
      experimental field study of natural populations of Arabidopsis, I tested the
      assumption that plant resistance has fitness costs. Models of the evolution of
      resistance assume a cost, which is envisioned as a reduction in fitness in the
      absence of natural enemies, such as insect herbivores and pathogens. The presumed
      basis of this cost is the diversion of limiting resources away from present and
      future growth and reproduction. Recent failures to detect allocation costs of
      resistance to herbivores have raised questions about whether costs exist and,
      thus, about the appropriateness of theories that postulate such costs. I found
      genetic variation for two traits commonly thought to function as resistance
      characters: trichome density and total glucosinolate concentration. Under field
      conditions, these characters both reduced damage by the natural assemblage of
      herbivores and exhibited significant fitness costs.

PMID- 18811422
TI  - Allocation to sexual versus nonsexual disease transmission.
AB  - Many diseases have both sexual and nonsexual transmission routes, and closely
      related diseases often differ in their degree of sexual transmission. We
      investigate the evolution of transmission mode as a function of host social and
      mating structure using a model in which disease transmission is explicitly
      dependent on the numbers of sexual and nonsexual contacts (which are themselves a
      function of population density) and per-contact infection probabilities. Most
      generally, and in the absence of trade-offs between the degree of sexual
      transmission and effects on host fecundity and mortality, nonsexual transmission
      is favored above the social-sexual crossover point (the host density at which the
      number of nonsexual contacts exceeds the number of sexual contacts), while sexual
      transmission is favored below this point. When changes in allocation to the two
      transmission modes are accompanied by changes in mortality or fecundity, both
      mixed and pure transmission strategies can be favored. If invading genotypes
      differ substantially from resident genotypes, genetic polymorphism in
      transmission mode is possible. The evolutionary outcomes are predictable from a
      knowledge of the equilibrium population sizes in relation to the social-sexual
      crossover point. Our results also show that predictions about dynamic outcomes,
      based on rates of invasion for single pathogens into healthy populations, do not
      adequately describe the resulting disease prevalence nor predict the subsequent
      evolutionary dynamics; once invasion of a pathogen has occurred, the conditions
      for spread of a second pathogen are themselves altered. If the host is considered
      as a single resource, our results show that two pathogens may coexist on a single
      resource if they use that resource differentially and have differential feedbacks
      on resource abundance; such resource feedback effects may be present in other
      biological systems.

PMID- 18811423
TI  - Sexual conflict and the energetic costs of mating and mate choice in water
      striders.
AB  - Analyses of intersexual conflicts of interest over courtship, mating, or mate
      guarding require an understanding of the physiological costs of sexual
      interaction. Repeated respirometric measures of energetic expenditure were taken
      on female Aquarius remigis while unladen and while carrying a mating male, a
      small metal weight, or a euthanized male. Unladen "cruising" locomotion consumed
      an average of 334.6 microW of energy (82 J kg-1 m-1); this estimate of the cost
      of locomotion coincides with measures from voluntarily locomoting arthropods of
      similar mass and represents the first energetic measure of skating on a water
      surface. Cruising females carrying males or metal weights consumed 24% and 28%
      more energy than unladen females, respectively. Females engaged in "escape"
      locomotion consumed 43% more energy while carrying a male than while unladen.
      Further, our study shows that premating struggles, and therefore selective mating
      decisions, are energetically costly. Struggling females consumed an average of
      936.6 microW, a 126% increase compared to cruising, nonstruggling females, and
      64% more than mating females engaged in escape locomotion. We develop a
      quantitative model showing that at a certain harassment rate threshold, accepting
      superfluous matings becomes the "best of a bad job" for females.

PMID- 18811424
TI  - Adaptive immune responses are linked to the mating system of arvicoline rodents.
AB  - Males generally exhibit reduced immune responses and greater susceptibility to
      disease than females. The suppressive effect of testosterone on immune function
      is hypothesized to be one reason why males have lower immune responses than
      females. Presumably, this effect of testosterone should be more pronounced among
      polygynous than monogamous species because circulating testosterone is higher
      among polygynous than monogamous males. The present study examined the extent to
      which sex differences in specific humoral immunity are related to the endocrine
      status and mating system of two arvicoline rodents. Humoral immunity was
      evaluated among polygynous meadow voles (Microtus pennsylvanicus) and monogamous
      prairie voles (Microtus ochrogaster) by challenging them with the novel antigen
      keyhole limpet hemocyanin (KLH) and assessing specific immune responses 5, 10,
      and 15 d following immunization. Overall, meadow voles mounted higher anti-KLH
      IgM and IgG responses than prairie voles did. Sex differences were also apparent
      for anti-KLH IgM responses; male meadow voles mounted higher antibody responses
      than conspecific females, whereas female prairie voles mounted greater responses
      to KLH than did conspecific males. Male meadow voles had significantly higher
      testosterone concentrations and reproductive organ mass than male prairie voles
      did but had elevated immune responses, suggesting that testosterone may not be
      the primary factor involved in the observed sex and species differences in immune
      responses. Species and sex differences in corticosterone concentrations were also
      evident and may contribute to the observed differences in immune function. The
      influence of extrinsic factors on immune function is also discussed. Taken
      together, these data provide evidence that the mating system may influence
      endocrine-immune interactions.

PMID- 18811425
TI  - Some methodological issues in macroecology.
AB  - Recent years have seen the emergence of "macroecology" as a distinct research
      program in biology. It is concerned with geographical scale patterns in
      assemblage structure and, as such, of necessity relies heavily on approaches that
      are nonexperimental and that depend on the availability of reliable information
      for large numbers of species. This gives rise to a particular set of analytical
      issues that need to be addressed when conducting studies of macroecological
      patterns. In this article, we draw attention to nine such issues that we consider
      to be of particular importance. Our aim is to aid the development of what we
      believe to be an important subject area by identifying some of the more common
      problems that may confound studies, as well as some of their solutions.

PMID- 18811426
TI  - On the capacity of macroparasites to control insect populations.
AB  - A graphical model of the population dynamics of macroparasites and their hosts is
      developed. Three principal means by which the parasites can be regulated are
      considered: reduction in host density as a result of parasite-induced host
      mortality, reduction in host density as a result of parasite-induced host
      sterility, and competition among parasites within multiply-infected hosts. The
      means by which parasites are regulated has a major effect on the degree to which
      they can depress host population densities. In particular, a parasite that
      sterilizes its host is expected to reduce host density more than one that causes
      an equivalent decline in host fitness through increased mortality. A special case
      of the model is developed for herbivorous insects that, in the absence of
      parasites, are limited by larval food resources. Parasites that are regulated via
      parasite-induced host sterility will control the insect populations below the
      level set by larval resources if the threshold host density for the parasites
      (N(T)) is less than the ratio of carrying capacity to net reproductive rate of
      the insects (K/R). Data are presented showing that all three means of parasite
      regulation, but especially parasite-induced host sterility, can operate in
      Howardula aoronymphium, a nematode parasite of mycophagous Drosophila flies. Data
      from a field cage experiment show that, if these nematodes are regulated
      primarily via reductions in host density due to this sterility, the parameters
      N(T), K, and R are such that Howardula is likely to play an important role in
      controlling Drosophila populations. However, this conclusion must be tempered by
      the fact that these nematodes also cause increased host mortality and experience
      within-host competition, making the conditions for parasite control of the flies
      more stringent.

PMID- 18811427
TI  - Leaf size, sapling allometry, and Corner's rules: phylogeny and correlated
      evolution in maples (Acer).
AB  - We studied the evolution of leaf size, sapling canopy allometry, and related
      traits in 17 Acer species growing in the understory of temperate deciduous
      forests, using parsimony methods, randomization tests, and independent contrasts
      calculated on a phylogeny inferred from nuclear ribosomal internal transcribed
      spacer (ITS) sequences. Bivariate correlations and multivariate analyses
      indicated two independent suites of coevolving traits, and the results were
      robust over a range of alternative phylogenies. The first suite consisted of
      strong positive correlations among twig thickness, leaf size, inflorescence
      length, and branch spacing (Corner's rules). Seed size and mature height were
      also weakly correlated with these traits. The second suite reflected aspects of
      sapling crown allometry, including crown size, stem diameter, and total leaf
      area, which appear to be related to shade tolerance. There was a weak negative
      correlation between sapling crown size and mature height, but no correlation with
      leaf or seed size. Most correlations were similar in magnitude for ahistorical
      and independent contrasts analyses, and discrepancies between these two measures
      were greater in traits with lower levels of convergent evolution. The
      evolutionary correlations among twig, leaf, seed, inflorescence, and canopy
      dimensions emphasize the need for integrated theories of evolution and function
      of these disparate traits.

PMID- 18811428
TI  - "A taste for the beautiful": latent aesthetic mate preferences for white crests
      in two species of Australian grassfinches.
AB  - Darwin first hypothesized that bright colors and elaborate ornamentation of male
      animals evolved in response to the "aesthetic" mate preferences of females. By
      this reasoning, potentially costly male secondary sexual traits may evolve not in
      response to selection for demonstration of vigor but, rather, in response to
      latent, nonfunctional preferences by females. Recent comparative evidence for
      this phenomenon is equivocal. Here we present experimental evidence that two
      avian species from a lineage devoid of crested species have mate preferences for
      opposite sex conspecifics wearing artificial white crests. Other colors of crests
      that have been studied are not preferred. Preferences for white crests did not
      diminish over the longest experimental interval (12 wk). These results are
      additional powerful evidence for highly structured aesthetic mate preferences in
      estrildine finches. Sex differences in the expression of preferences, and the
      widespread occurrence of facial ornamentation in birds, suggest that the
      preference "structure" is influenced by the central nervous system. We
      hypothesize that aesthetic preferences are a potent force in the early evolution
      of sexually selected traits, and that "indicator" traits evolve secondarily from
      traits initially favored by aesthetic preferences.

PMID- 18811429
TI  - Effects of disturbance on species diversity: a multitrophic perspective.
AB  - Models of the effects of disturbance on ecological communities have largely
      considered communities of competing species at a single trophic level. In
      contrast, most real communities have multiple interacting trophic levels. I
      explored several versions of simple single- and multitrophic models to determine
      whether predictions of the intermediate disturbance hypothesis (IDH), derived
      from considering only a single trophic level, apply to multitrophic situations.
      The IDH was predicted by models of competing species at a single trophic level
      but did not hold in many situations with more natural trophic structure. In
      general, basal species in a food web tended to follow the IDH, whereas
      competitors at top trophic levels did not. Additional analyses indicated that
      outside immigration interacted with trophic structure to produce widely differing
      predictions about the consequences of disturbance and that density-dependent
      disturbance events could recapture the IDH in some multiple trophic level
      situations. Model predictions matched the results of empirical studies to date:
      the IDH has generally been supported for species competing for nondynamic basal
      resources but not for mobile aquatic invertebrates at higher trophic levels. The
      model analysis also verified basic predictions of verbal models addressing the
      effects of physical stress. Three different aspects of disturbance and their
      contributions to species coexistence were identified: changes in average
      mortality rates, changes in temporal variability, and changes in spatial
      heterogeneity. The results indicate that the IDH should be applied with caution
      to real multitrophic communities.

PMID- 18811430
TI  - Levels of mate recognition within and between two Drosophila species and their
      hybrids.
AB  - If sexual selection is to result in speciation, traits involved in mate choice
      within species need to be capable of producing sexual isolation between species.
      We investigated the association between mate choice and sexual isolation using
      interspecific hybrids between two sibling species, Drosophila serrata and
      Drosophila birchii. A perfuming experiment demonstrated that olfaction was
      involved in the sexual isolation between the two species. A quantitative genetic
      analysis using 30 populations of hybrids between the two species indicated that
      mating success in hybrid individuals was predominately determined by cuticular
      hydrocarbons; the average genetic correlation between mating success and
      cuticular hydrocarbon profile was 0.84, and in some instances exceeded 0.95.
      Multivariate analysis of the cuticular hydrocarbons of the two species revealed
      that there were three independent blends of cuticular hydrocarbons that separated
      three levels of organization: species, sex, and sex within species. The
      hydrocarbons used by hybrids in mate choice included those that separated the two
      species, demonstrating that species-specific characters may be used in mate
      choice within populations. The interspecific reciprocal cross had major effect on
      which cuticular hydrocarbons were associated with mating success, indicating that
      the expression of the cuticular hydrocarbons was strongly sex linked.

PMID- 18811431
TI  - Reconciling classical and individual-based approaches in theoretical population
      ecology: a protocol for extracting population parameters from individual-based
      models.
AB  - The two main approaches in theoretical population ecology-the classical approach
      using differential equations and the approach using individual-based modeling
      seem to be incompatible. Linked to these two approaches are two different
      timescales: population dynamics and behavior or physiology. Thus, the question of
      the relationship between classical and individual-based approaches is related to
      the question of the mutual relationship between processes on the population and
      the behavioral timescales. We present a simple protocol that allows the two
      different approaches to be reconciled by making explicit use of the fact that
      processes operating on two different timescales can be treated separately. Using
      an individual-based model of nomadic birds as an example, we extract the
      population growth rate by deactivating all demographic processes-in other words,
      the individuals behave but do not age, die, or reproduce. The growth rate closely
      matches the logistic growth rate for a wide range of parameters. The implications
      of this result and the conditions for applying the protocol to other individual
      based models are discussed. Since in physics the technique of separating
      timescales is linked to some concepts of self-organization, we believe that the
      protocol will also help to develop concepts of self-organization in ecology.

PMID- 18811432
TI  - The regulation of phenotypic plasticity of eyespots in the butterfly Bicyclus
      anynana.
AB  - We use an outcrossed stock and selected lines of Bicyclus anynana in combination
      with measurements and manipulations of ecdysteroid hormones in early pupae to
      examine the regulation of eyespot size in adult butterflies. The eyespots on the
      ventral wing surfaces express adaptive phenotypic plasticity in response to the
      dry-wet seasonal environments of the butterflies. Larvae reared at low or high
      temperatures produce adults with small or large ventral eyespots, respectively.
      Our experiments examine the role of ecdysteroids in mediating this phenotypic
      plasticity. Higher titers of ecdysteroids shortly after pupation yield larger
      ventral wing eyespots. There is an uncoupling of the ventral eyespots and those
      on the dorsal forewing. The latter do not show phenotypic plasticity. They show
      very little response to rearing temperature, and variation in their size is not
      associated with differences in the dynamics of ecdysteroids in early pupae. A
      testable hypothesis in terms of the distribution of hormone receptors in the
      developmental "organizers" or foci of the eyespots is proposed to account for how
      some eyespots express plasticity while others do not.

PMID- 18811433
TI  - A model of particle capture by bryozoans in turbulent flow: significance of
      colony form.
AB  - A hydrodynamic model was developed to examine particle capture by lophophores of
      encrusting bryozoans. Particle capture rate is predicted to increase with
      increasing speed of the feeding current. There should be a large feeding
      advantage when lophophores are tightly packed and excurrents are vented through
      chimneys. This prediction contradicts conclusions of an earlier model study and
      suggests that selection for colony integration has a basis in the acquisition of
      food. If lophophores are not tightly packed, particle-capture patterns depend on
      two key ratios: the advection ratio (feeding current velocity to shear velocity)
      and the separation ratio (lophophore spacing to lophophore diameter). At high
      separation ratios, particle capture rates should be fairly uniform among zooids.
      At high advection ratios, lophophores located near the upstream colony edge
      should experience higher rates of particle capture. Rates of particle capture in
      turbulent flows should greatly exceed those in laminar flows (of identical speed)
      when excurrent waters are locally remixed into the flow above lophophores.
      However, when lophophores are tightly packed and excurrents are vented through
      chimneys, feeding rates should be identical in turbulent and laminar flows. Thus,
      colonies that vent excurrents through chimneys may be uniquely able to exploit
      weak laminar flows.

PMID- 18811434
TI  - Seasonality, optimal foraging, and prey coexistence.
AB  - Several empirical studies suggest that herbivores may promote coexistence between
      plants by relaxing the strength of resource competition. In contrast, recent
      mathematical models predict that food-limited herbivory instead cause exclusion
      through apparent competition, regardless of whether herbivore selectivity is
      constant or density dependent. This study extends existing theory to consider a
      strongly seasonal system. Herbivores with fixed diet preferences have the same
      effect regardless of seasonality, but there is a marked difference when the diet
      selectivity of herbivores conforms to a simple optimal-foraging model. An
      optimally foraging herbivore in a seasonal environment is able to promote plant
      coexistence among many species. The mechanism involves diet switching, occurring
      over narrow density intervals. For this to have an effect in a nonseasonal model,
      equilibrium resource densities must be in this interval, which requires close
      parameter fitting. In seasonal environments, resource densities change through
      the year and may frequently move across narrow regions in which diet changes
      occur. The potential of gray-sided voles to promote coexistence between two
      arctic dwarf shrubs is evaluated in terms of the model. For this system, it is
      shown that vole herbivory has the potential to reverse competitive dominance.

PMID- 18811435
TI  - Local movement and edge effects on competition and coexistence in ephemeral-patch
      models.
AB  - For insects exploiting spatially structured arrays of resource patches (host
      plants, fungi, carrion, etc.), the distribution of individuals among patches can
      have important consequences for the coexistence of competitors. In general,
      intraspecific aggregation of consumer individuals over the landscape of patches
      stabilizes competition. Oviposition behavior of individual females can generate
      aggregation of larvae across patches and, therefore, strongly influences the
      outcome of competition between co-occurring species. We used simulation models to
      evaluate the consequences (for the coexistence of competitors) of different
      movement behaviors by females before and between oviposition events. Coexistence
      times increase when females are more likely to travel among neighboring patches
      than among distant ones. Coexistence times are also longer when females begin egg
      laying near the site of their emergence. Preoviposition dispersal is, therefore,
      destabilizing. We also considered responses by females to edges of resource
      arrays. Edge effects are generally stabilizing, delaying competitive exclusion by
      increasing larval aggregation, but different responses to edges have dramatically
      different effects on coexistence. The longest coexistence times occur when edges
      are "sticky", such that females encountering an edge tend to remain there.

PMID- 18811436
TI  - Secondary metabolites in fleshy fruits: are adaptive explanations needed?

PMID- 18811437
TI  - Secondary metabolites as traits of ripe fleshy fruits: a response to Eriksson and
      Ehrlen.

PMID- 18811442
TI  - Population dynamics, disturbance, and pattern evolution: identifying the
      fundamental scales of organization in a model ecosystem.
AB  - We used auto- and cross-correlation analysis and Ripley's K-function analysis to
      analyze spatiotemporal pattern evolution in a spatially explicit simulation model
      of a semiarid shrubland (Karoo, South Africa) and to determine the impact of
      small-scale disturbances on system dynamics. Without disturnities bance, local
      dynamics were driven by a pattern of cyclic succession, where 'colonizer' and
      'successor' species alternately replaced each other. This results in a strong
      pattern of negative correlation in the temporal distribution of colonizer and
      successor species. As disturbance rates were increased, the relationship shifted
      from being negatively correlated in time to being positively correlated-the
      dynamics became decoupled from the ecologically driven cyclic succession and were
      increasingly influenced by abiotic factors (e.g., rainfall events). Further
      analysis of the spatial relationships among colonizer and successor species
      showed that, without disturbance, periods of attraction and repulsion between
      colonizer and successor species alternate cyclically at intermediate spatial
      scales. This was due to the spatial 'memory' embedded in the system through the
      process of cyclic succession. With the addition of disturbance, this pattern
      breaks down, although there is some indication of increasing ecological
      organization at broader spatial scales. We suggest that many of the insights that
      can be gained through spatially explicit models will only be obtained through a
      direct analysis of the spatial patterns produced.

PMID- 18811443
TI  - Variation in lifetime male fitness in Ipomopsis aggregata: tests of sex
      allocation theory.
AB  - Sex allocation theory assumes that a shift in allocation of resources to male
      function both increases male fitness and decreases female fitness. Moreover, the
      shapes of these fitness gain functions determine whether hermaphroditism or
      another breeding system is evolutionarily stable. In this article, I first
      outline information needed to measure these functions in flowering plants. I then
      use paternity analysis to describe the shapes of the fitness gain functions in
      natural populations of the hermaphroditic herb Ipomopsis aggregata. I also
      explore the relationships of male fitness (number of seeds sired) and female
      fitness (number of seeds produced) to the number of flowers produced by a plant.
      Plants with greater investment of biomass in the androecium, compared to the
      gynoecium and seeds, showed increased success at siring seeds, assumed by the
      models. That sex allocation trait, however, explained only 9% of the variance in
      estimates of male fitness. The shapes of the fitness gain functions were
      consistent with theoretical expectations for a hermaphroditic plant, but the
      model predicted a more female-biased evolutionarily stable strategy (ESS)
      allocation than was observed. These results lend only partial support the
      classical sex allocation model.

PMID- 18811444
TI  - Optimal floating and queuing strategies: consequences for density dependence and
      habitat loss.
AB  - Field studies of many vertebrates show that some individuals (floaters) do not
      defend territories even when there is space for them to do so. We show that the
      evolutionarily stable strategy (ESS) for the threshold territory quality at which
      floating takes place is that which maximizes the size of the floating population
      (but not the total population, breeding population, or reproductive output). The
      ESS is solved separately for two assumptions: whether individuals wait to occupy
      a single territory or multiple territories and whether queuing rules are strict
      or if all waiting individuals are equally likely to obtain the next territory.
      The four combinations of these assumptions all give the same evolutionarily
      stable population size of both floaters and breeders. At the ESS, only
      territories with expected lifetime reproductive success (LRS) exceeding 1 should
      be occupied, which introduces a limit to ideal habitat selection. The behavioral
      decision to float alters the shape of the density-dependent response, reduces the
      equilibrium population size, and affects the response of the population to
      habitat loss. Specifically, the floater: breeder ratio is directly related to
      average breeding habitat quality, and the floater population size will decrease
      more than the breeding population size if better than average quality habitat is
      lost.

PMID- 18811445
TI  - Mass- and density-dependent reproductive success and reproductive costs in a
      capital breeder.
AB  - For capital breeders, mass may affect reproductive potential. Reproductive
      expenditure may reduce future reproductive potential, particularly when resources
      are scarce. To test the hypothesis that reproductive success and the costs of
      reproduction vary according to mass and population density, we analyzed 25 yr of
      data on bighorn ewes (Ovis canadensis). The number of adult females was first
      limited by yearly removals, then allowed to triple. We found no survival costs of
      reproduction for ewes aged 4-7 yr. For ewes aged 8-14 yr, survival was density
      dependent for barren ewes but not for ewes that weaned lambs. Failure to lamb was
      rare and negatively correlated with fertility the following year. At low
      population density, lactation had a negative effect on mass gain but had a
      limited reproductive cost. At high density, heavy ewes had higher reproductive
      success than light ewes, and the reproductive cost and somatic costs of
      reproduction increased. The cost of reproduction was greater for light than for
      heavy ewes. Survival of weaned lambs to 1 yr was affected by population density
      but not by maternal mass or previous reproductive success. In large mammals,
      manipulations of reproductive effort are problematic, but long-term monitoring of
      individual mass and reproductive success under varying conditions of resource
      availability can provide insights into the evolution of life histories.

PMID- 18811446
TI  - No evidence for inbreeding avoidance in a natural population of song sparrows
      (Melospiza melodia).
AB  - We studied mate choice and inbreeding avoidance a natural population of song
      sparrows (Melospiza melodia) on Mandarte Island, Canada. Inbreeding occurred
      regularly: 59% all matings were between known relatives. We tested for inbreeding
      avoidance by comparing the observed levels of inbreeding to those expected if
      mate choice had been random with respect to relatedness. Independent of our
      assumptions about the availability of mates in the random mating model, we found
      that the expected and observed distributions of inbreeding coefficients were
      similar, as was the expected and observed frequency of close (f >/= 0.125)
      inbreeding. Furthermore, there was no difference in relatedness observed pairs
      and those that would have resulted had birds mated instead with their nearest
      neighbors. The only evidence to suggest any inbreeding avoidance was a reduced
      rate of parent-offspring matings as compared to one random mating model but not
      the other. Hence, despite substantial inbreeding depression in this population,
      we found little evidence for inbreeding avoidance through mate choice. We present
      a simple model to suggest that variation in inbreeding avoidance behaviors in
      birds may arise from differences in survival rates: in species with low survival
      rates, the costs of forfeiting matings to avoid inbreeding may exceed the costs
      of inbreeding.

PMID- 18811447
TI  - Predator-mediated interactions between and within guilds of nesting songbirds:
      experimental and observational evidence.
AB  - Apparent competition (i.e., a mutually negative indirect interaction between prey
      species through shared predation) arises when predator abundance or foraging
      effort increases with total prey availability. We review and formalize several
      patch-use models from which we derive predictions for how the degree of coupling
      (from the predators' perspective) between nesting guilds (defined as species
      nesting within a vegetation stratum) affects the outcome of shared predation. We
      then determine which model best applies to nest predation on woodland songbirds
      and artificial nests by a natural population of raccoons. Using artificial nests,
      we showed that increasing the density of nests placed either in shrubs or on the
      ground increased overall predation (i.e., proportion of nests) on both types. We
      also tested for apparent competition between American robin and wood thrush, two
      coexisting woodland songbirds that commonly nest within the shrub stratum. Nest
      predation increased for wood thrushes but not robins as the combined density of
      robin and thrush nests within two individual substrate types, Lonicera and
      Rhamnus, increased. Thus, we documented apparent competition both within and
      among nesting guilds. We discuss the possible relevance of this interaction in
      determining species diversity, particularly in the light of increasing generalist
      nest predators through anthropogenically driven changes in human-altered
      landscapes.

PMID- 18811448
TI  - Colony size and individual fitness in the social spider Anelosimus eximius.
AB  - The effects of colony size on individual fitness and its components were
      investigated in artificially established and natural colonies of the social
      spider Anelosimus eximius (Araneae: Theridiidae). In the tropical rain forest
      understory at a site in eastern Ecuador, females in colonies containing between
      23-107 females had india significantly higher lifetime reproductive success than
      females in smaller colonies. Among larger colonies, this trend apparently
      reversed. This overall fitness function was a result of the conflicting effects
      of colony size on different components of fitness. In particular, the probability
      of offspring survival to maturity increased with colony size while the
      probability of a female reproducing within the colonies decreased with colony
      size. Average clutch size increased with colony size when few or no wasp
      parasitoids were present in the egg sacs. With a high incidence of egg sac
      parasitoids, this effect disappeared because larger colonies were more likely to
      be infected. The product of the three fitness components measured-probability of
      female reproduction, average clutch size, and offspring survival-produced a
      function that is consistent with direct estimates of the average female lifetime
      reproductive success obtained by dividing the total number of offspring maturing
      in a colony by the number of females in the parental generation. Selection,
      therefore, should favor group living and intermediate colony sizes in this social
      spider.

PMID- 18811449
TI  - Within-brood competition and the optimal partitioning of parental investment.
AB  - In this article, we introduce a simple within-brood competitive growth model that
      maximizes parental fitness in unpredictable food conditions in species that
      exhibit parental care, progressive provisioning, and an initial brood
      overproduction. We argue that competition between siblings may provide a
      proximate mechanism for parents to adjust the number of surviving offspring or
      the social organization of the group in social species to food conditions.

PMID- 18811450
TI  - The influence of dispersal and diet breadth on patterns of genetic isolation by
      distance in phytophagous insects.
AB  - To determine the effects of dispersal ability and diet breadth on population
      genetic structure, we reviewed the allozyme literature and estimated genetic
      isolation by distance (IBD) for 43 species/host races of phytophagous insects.
      Subsequently, we tested two opposing hypotheses regarding the influence of
      dispersal ability on IBD: that IBD slopes do not vary with mobility, but that
      intercepts increase with mobility, and, alternatively, that IBD slopes vary with
      dispersal ability. We found that from tens of kilometers to more than 1,000 km,
      IBD is weak in sedentary and highly mobile species but pronounced in moderately
      mobile species. We attribute the weak IBD in strong dispersers to the
      homogenizing effects of gene flow, whereas in sedentary species, limited gene
      flow allows nearly all populations to diverge. In intermediate dispersers,
      genetic homogeneity is achieved at small spatial scales, but limited dispersal
      promotes genetic divergence over long distances. We also tested the hypothesis
      that IBD increases with decreasing diet breadth. We discovered no such pattern,
      casting doubt on the supposition that specialization promotes speciation by
      influencing population-genetic subdivision. Finally, we found that the number of
      populations is a more important consideration than the number of polymorphic loci
      in studies of IBD.

PMID- 18811451
TI  - Chaos in the Pacific's coral reef bleaching cycle.
AB  - There is no simple explanation for the unusual increase in coral reef bleaching
      events that have been occurring on a global scale over the last 2 decades. Recent
      studies focusing on this problem reveal that mass bleaching events have a strong
      periodic component, arising every 3-4 yr in step with the El Nino climatic
      phenomenon. To explore this possibility further, we examine a simple
      oceanographic-ecological model designed to simulate the warm and cool phases of
      the Pacific Ocean cycle and gauge its effect on local coral reefs. This allows us
      to identify causes for localized 'hot spots' in the ocean, whose high sea surface
      temperatures have disastrous consequences for corals. The underlying wave
      dynamics of the model lead to chaotic oscillations (every 3-4 yr), which help
      explain the coexistence of both order and irregularity in the dynamics of mass
      bleaching. The model makes use of a temperature threshold mechanism-a bleaching
      event is triggered whenever temperature anomalies exceed a critical level. In a
      variable environment, the threshold mechanism is sensitive to background
      fluctuations, and their effects are studied by making use of a 'stochastic
      resonance' formulation. Global climate change and other trends in external
      background environmental conditions are all shown to strongly influence the
      distribution of mass coral bleaching events.

PMID- 18811452
TI  - Food web stability: the influence of trophic flows across habitats.
AB  - In nature, fluxes across habitats often bring both nutrient and energetic
      resources into areas of low productivity from areas of higher productivity. These
      inputs can alter consumption rates of consumer and predator species in the
      recipient food webs, thereby influencing food web stability. Starting from a well
      studied tritrophic food chain model, we investigated the impact of allochthonous
      inputs on the stability of a simple food web model. We considered the effects of
      allochthonous inputs on stability of the model using four sets of biologically
      plausible parameters that represent different dynamical outcomes. We found that
      low levels of allochthonous inputs stabilize food web dynamics when species
      preferentially feed on the autochthonous sources, while either increasing the
      input level or changing the feeding preference to favor allochthonous inputs, or
      both, led to a decoupling of the food chain that could result in the loss of one
      or all species. We argue that allochthonous inputs are important sources of
      productivity in many food webs and their influence needs to be studied further.
      This is especially important in the various systems, such as caves, headwater
      streams, and some small marine islands, in which more energy enters the food web
      from allochthonous inputs than from autochthonous inputs.

PMID- 18811453
TI  - A new look at relationships between size at maturity and asymptotic size.
AB  - Comparative studies have revealed positive correlations between size at maturity
      and asymptotic size in several taxa with asymptotic growth after maturity. Using
      a simple growth model, we show that positive correlations between size at
      maturity and asymptotic size are predicted for different individuals in the same
      species if growth costs of reproduction are inversely related to size at
      maturity. Several processes might lead to higher growth costs of reproduction for
      smaller individuals; these include effects of body size on competition for
      resources required for breeding, on the space available within the body cavity
      for food processing in gravid individuals, and on the costs of transporting eggs
      or young in relation to the total energy budget. We confirm several key elements
      of the growth model using data from female Iguana iguana lizards, including the
      novel assumption that instantaneous growth rates of adults of the same length
      will be positively related to their length at maturity. These analyses suggest a
      simple and possibly general explanation for positive correlations between size at
      maturity and asymptotic size within-and perhaps also among-species that continue
      to grow after maturity.

PMID- 18811454
TI  - Transcontinental crashes of insect populations?

PMID- 18811455
TI  - Spatial scale and the spread of a fungal pathogen of gypsy moth.

PMID- 18811458
TI  - "Multiperc" for complete staghorn calculus.

PMID- 18811459
TI  - A single percutaneous access and flexible nephroscopy is the best treatment for a
      full staghorn calculus.

PMID- 18811463
TI  - Flexible ureteroscopy is the ideal choice to manage a 1.5 cm diameter lower-pole
      stone.

PMID- 18811464
TI  - Flexible ureterorenoscopic management of lower-pole stone: does the scope make
      the difference?

PMID- 18811465
TI  - Management of lower-pole stones of 0.8 to 1.5 cm maximal diameter by the
      minimally invasive percutaneous approach.

PMID- 18811470
TI  - Percutaneous nephrolithotomy: leave a tube!

PMID- 18811471
TI  - Tubeless percutaneous nephrolithotomy: a new standard in percutaneous renal
      surgery.

PMID- 18811475
TI  - Balloon dilation of nephrostomy tracts.

PMID- 18811476
TI  - Percutaneous nephrolithotomy: why do we use rigid dilators?

PMID- 18811477
TI  - Prone retrograde laser lithotripsy facilitates endoscope-guided percutaneous
      renal access for staghorn calculi: two scopes are better than one.

PMID- 18811482
TI  - Endopyelotomy: the best solution for patients with stones associated with
      ureteropelvic junction obstruction.

PMID- 18811483
TI  - The case for percutaneous endopyeloplasty.

PMID- 18811484
TI  - Secondary ureteropelvic junction obstruction and renal calculus after failed open
      pyeloplasty: laparoscopic management.

PMID- 18811489
TI  - Radiofrequency ablation: the preferred minimally invasive treatment.

PMID- 18811490
TI  - The case for laparoscopic partial nephrectomy.

PMID- 18811491
TI  - Small renal masses: the case for cryoablation.

PMID- 18811496
TI  - Partial nephrectomy for renal cell carcinoma: trust suturing.

PMID- 18811497
TI  - Laparoscopic partial nephrectomy without hilar control.

PMID- 18811501
TI  - Laparoscopic adrenalectomy for a 6-cm pheochromocytoma of the left adrenal gland.

PMID- 18811502
TI  - Laparoscopic adrenalectomy for a 6-cm left adrenal pheochromocytoma with
      needlescopic instruments.

PMID- 18811506
TI  - Management of the distal ureter and bladder cuff during nephroureterectomy for
      transitional cell carcinoma.

PMID- 18811507
TI  - The Northwestern flexible endoscopic technique of management of the distal ureter
      during laparoscopic nephroureterectomy.

PMID- 18811511
TI  - Vascular pedicle control during robot-assisted and laparoscopic prostatectomy:
      bulldog clamp and suturing technique.

PMID- 18811512
TI  - Laparoscopic nerve-sparing prostatectomy: the use of clips for vascular control.

PMID- 18811516
TI  - Feasibility, technique, and principles of tension- and energy-free laparoscopic
      radical prostatectomy with lateral intrafascial dissection of the neurovascular
      bundles with the use of a high-definition optical device.

PMID- 18811517
TI  - Extraperitoneal endoscopic radical prostatectomy for prostate cancer in a 63-year
      old man with a previous abdominal incision for pelvic cancer.

PMID- 18811518
TI  - Transrectal ultrasound-guided, energy-free, nerve-sparing laparoscopic radical
      prostatectomy.

PMID- 18811520
TI  - Optimization of the vesicourethral anastomotic model in laparoscopic
      prostatectomy performed on large prostates.

PMID- 18811521
TI  - Management of a large gap between bladder and urethra immediately
      postprostatectomy.

PMID- 18811524
TI  - Laparoscopic extraperitoneal ascending nerve-sparing radical prostatectomy: an
      effective and safe technique for apical tumors.

PMID- 18811525
TI  - The case for antegrade dissection.

PMID- 18811529
TI  - The case for postoperative PDE-5 inhibitor drug treatment after radical
      prostatectomy.

PMID- 18811530
TI  - What is adequate management to preserve erectile function after unilateral nerve
      sparing radical prostatectomy?

PMID- 18811534
TI  - The case for robot-assisted radical prostatectomy.

PMID- 18811535
TI  - The case for laparoscopic radical prostatectomy.

PMID- 18811539
TI  - Laparoscopic radical prostatectomy: an established minimally invasive procedure
      with proven oncologic track record.

PMID- 18811540
TI  - The case for cryoablation of prostate cancer.

PMID- 18811544
TI  - The case for open radical cystoprostatectomy and urinary reconstruction.

PMID- 18811545
TI  - Laparoscopic radical cystectomy: formidable challenge to the gold standard.

PMID- 18811546
TI  - Robot-assisted radical cystectomy.

PMID- 18811551
TI  - Percutaneous resection of upper tract transitional cell carcinoma in a solitary
      kidney after cystectomy and continent orthotopic urinary diversion.

PMID- 18811552
TI  - Ureteroscopic treatment of pelvic renal tumor in a solitary kidney with
      orthotopic neobladder.

PMID- 18811556
TI  - Metal stents for the management of malignant ureteral obstruction.

PMID- 18811557
TI  - Malignant ureteral obstruction: the case for plastic ureteral stents.

PMID- 18811561
TI  - Bipolar TURP treatment for BPH refractory to medication:the past, present, and
      future surgical reference standard.

PMID- 18811562
TI  - Holmium laser enucleation of the prostate is the single best treatment for benign
      prostatic hyperplasia refractory to medication.

PMID- 18811563
TI  - Photoselective vaporization of the prostate to manage benign prostatic
      hyperplasia.

PMID- 18811567
TI  - Robotic urethrovesical anastomosis: combining running and interrupted sutures.

PMID- 18811568
TI  - Totally tubeless percutaneous nephrolithotomy in renal anomalies.
AB  - OBJECTIVES: To assess the outcome and safety of the totally tubeless percutaneous
      nephrolithotomy in renal anomalies. PATIENTS AND METHODS: During a prospective
      clinical trial from December 2002 to November 2006, 60 patients with renal
      anomalies and nephrolithiasis were included in our study. The anomalies consisted
      of the horseshoe kidney, rotational anomalies of pyelocalyceal system, and
      ectopic kidney. The patients were randomly divided in two groups: the "totally
      tubeless" procedures performed in 30 patients (the nephrostomy tube and internal
      stent were not used in any patient), and 30 patients underwent standard
      percutaneous nephrolithotomy (PCNL; using both nephrostomy tube and ureteral
      stent). The incidence of complications, hospital stay, transfusion requirements,
      and stone-free rates were compared in the two groups. RESULTS: In the group of
      patients that underwent totally tubeless PCNL for the stone extraction, the mean
      stone burden was 2.54 cm(2) (standard deviation [SD] = 0.96). Patients' stay in
      the hospital averaged 1.3 (SD = 0.43) days. The average analgesics requirement
      was 4.5 (SD = 1.6) mg of morphine. The patients returned to normal activity in 10
      (SD = 3.2) days. The postoperative complications were blood transfusion in one
      patient (3.3%) and fever in one patient (3.3%). An 83.3% stone-free rate was
      achieved. For the standard PCNL group, the mean stone size was 2.83 (SD = 0.76)
      cm(2), and the mean length of hospitalization was 2.6 (SD = 0.65) days. The
      average analgesics requirement was 10.4 (SD = 3.2) mg of morphine, and the time
      to return normal activity was 15.5 (SD = 3.2) days. Only 2 (6.7%) patients
      required a transfusion, and 1 (3.3%) patient had postoperative complications
      (penumothorax). Of the 30 patients, 86.7% became stone free. The differences
      between operation time, transfusion rates, complications, retreatment, and
      overall stone-free rate were not statistically significant in the two groups but
      days of hospitalization (P < 0.001), analgesics requirement (P < 0.001), and time
      of return tonormal activity (P < 0.001) were statistically significant.
      CONCLUSIONS: Totally tubeless percutaneous renal surgery is a safe and effective
      procedure in renal anomalies and can be performed in patients even with a
      moderate to large stone burden.

PMID- 18811569
TI  - Factors affecting fever following percutaneous nephrolithotomy: a prospective
      clinical study.
AB  - AIM: To evaluate the preoperative and intraoperative factors that might affect
      development of fever following percutaneous nephrolithotomy (PCNL) and to
      investigate the clinical significance of intraoperative microbiologic evaluation
      in managing postoperative infectious complications. PATIENTS AND METHODS: Sixty
      one consecutive patients who had undergone PCNL between October 2006 and June
      2007 were prospectively recruited into the study. Preoperative urine cultures and
      intraoperative stone and pelvic urine cultures were obtained from all patients.
      Postoperatively, patients were closely monitored for fever and other signs of
      systemic inflammatory response syndrome. RESULTS: Of 61 patients, 10 (16.8%) had
      at least one body temperature recorded at 38 degrees C (group 1), the remaining
      patients were afebrile (group 2). Fever was associated with a systemic
      inflammatory response syndrome in one patient (1.6%); in that patient, the
      antibiotic regimen was altered. There were statistically significantly more
      positive stone culture results for patients in group 1 than there were for
      patients in group 2 (5/10 versus 9/51, P < 0.05). There were statistically
      significantly more positive pelvic urine culture results for patients in group 1
      than there were for patients in group 2 (3/10 versus 2/51, P < 0.05). Patients in
      group 1 also had longer operative times and larger stone burdens than did
      patients in group 2. CONCLUSIONS: Intraoperative microbiologic evaluation may be
      important in postoperative antibiotic selection and should be routinely used.

PMID- 18811570
TI  - Safety and outcome of percutaneous nephrolithotomy in the elderly: retrospective
      comparison to a younger patient group.
AB  - AIM: To evaluate whether the overall safety and efficacy profile of percutaneous
      surgery for urinary stone disease in older (>70 years) patients might influence
      the decision for the procedure in the elderly. MATERIALS AND METHODS: A large
      database was created from our patients (n = 1058) who underwent percutaneous
      surgery for stone disease between 1991 and 2003 in the Scottish Lithotriptor
      Centre, including clinical and operation details for each case. Only percutaneous
      nephrolithotomy cases with full details were studied (n = 779) and were grouped
      into two age groups: (1) between 17 and 69 years and (2) over 70 years.
      Statistical analysis evaluated differences in terms of operation-related adverse
      events, stone-free success rates, and clinical success rates (including stone
      free cases and cases with residual fragments <4 mm). Further analysis was
      performed for the same endpoints after stratification of the patients by (1)
      previous stone procedures and (2) special clinical features. RESULTS: In the
      overall database, no statistically important differences were found between the
      two groups in terms of stone burden before surgery, adverse events rates,
      complete stone-free rates, and clinical success rates. However, a statistical
      trend toward higher clinical success rates in favor of the younger group was seen
      (P = 0.051). Stratification of our database according to previous stone disease
      procedures or special clinical or anatomic characteristics has only shown a
      statistically important difference for clinical success rates in favor of the
      older group without special features (P = 0.01). CONCLUSION: In experienced
      hands, age-related morbidity or age itself should not be a discouraging
      consideration when deciding on performing percutaneous nephrolithotomy, as the
      procedure is as equally feasible and safe in the elderly as in the younger
      patient population.

PMID- 18811571
TI  - Does a smaller tract in percutaneous nephrolithotomy contribute to high renal
      pelvic pressure and postoperative fever?
AB  - OBJECTIVE: High renal pelvic pressure brings systemic absorption of irrigation
      fluid containing bacteria or endotoxins, which leads to postoperative fever. We
      inspected the renal pelvic pressure (RPP) in vivo during minimally invasive
      percutaneous nephrolithotomy (MPCNL) to investigate whether a 14- to 18-French
      percutaneous tract and perfusion would bring high RPP and postoperative fever.
      PATIENTS AND METHODS: Between July 2005 and December 2007, 80 patients were
      selected for RPP measurement during MPCNL. The RPP was measured by a baroceptor
      connected to the open-ended ureteric catheter, which was indwelling retrogradely
      in the renal pelvic. A computer recorded the RPP each second, and all the data
      were evaluated statistically with SPSS 12.0 software. RESULTS: During MPCNL with
      14-, 16-, 18-, and double-16-French percutaneous tracts, the mean RPP was 24.55,
      16.49, 11.22, and 6.64 mm Hg, respectively. Logistical analysis suggested that
      postoperative fever did not correlate to gender (P = 0.195), age (P = 0.641),
      urinary tract infection (P = 0.663), white blood cell > or = 10 x 10(9)/L in
      routine postoperative blood examination (P = 0.751), or an occurrence of renal
      pelvic pressure > or = 30 mm Hg in the operation (P = 0.662), although infection
      calculi (P = 0.000), percutaneous tract (P = 0.029), mean RPP (P = 0.036), mean
      RPP > or = 20 mm Hg (P = 0.013), accumulated time of RPP > or = 30 mm Hg (P =
      0.010), and RPP > or = 30 mm Hg longer than 50 s (P = 0.024) may contribute a
      postoperative fever. CONCLUSION: Renal pelvic pressure generally remains lower
      than the backflow level (30 mm Hg) during MPCNL via a 14- to 18-French
      percutaneous tract. Any factors that brought about poor drainage would result in
      temporarily elevated RPP greater than 30 mm Hg, and many such occurrences of high
      pressure would have an accumulating effect, which means enough backflow to cause
      bacteremia and postoperative fever.

PMID- 18811572
TI  - Is retroperitoneal approach feasible for robotic dismembered pyeloplasty: initial
      experience and long-term results.
AB  - OBJECTIVES: To present our initial series of robotic-assisted retroperitoneal
      dismembered pyeloplasty in adults patients using the da Vinci Surgical System
      (Intuitive Surgical, Inc., Sunnyvale, CA). METHODS: Ten adult patients with
      unilateral ureteropelvic junction (UPJ) obstruction underwent robotic-assisted
      retroperitoneoscopic Anderson-Hynes dismembered pyeloplasty between February 2004
      and March 2005. UPJ obstruction was primary in six patients and secondary in four
      patients after failed endopyelotomy. Dismembered pyeloplasty was performed
      utilizing a retroperitoneal approach (developed by balloon dissection). Three
      retroperitoneal laparoscopic ports were placed for the robot, and a fourth port
      was used by the assistant. Robotic-assisted laparoscopic technique was utilized
      to perform the entire procedure in all cases. RESULTS: All cases (seven right,
      three left) were successfully completed using the robot without conversion to
      conventional laparoscopic or open technique. Median surgical time was 175 minutes
      (95% confidence interval [CI] 128-185), median estimated blood loss was 50 mL
      (95% CI, 26-62), and the median hospital stay was 48 hours (95% CI, 27-65). No
      complications occurred. At a mean follow-up of 30 months (range 24-36), clinical
      symptomatic assessment with a numeric pain scale, health-related quality of life
      evaluation with the Short Form 36 health survey, and functional assessment with
      Tc-99m-mercaptoacetyltriglycine, diuretic renography, and intravenous urogram
      demonstrated a successful outcome in all cases. CONCLUSIONS: Robotic-assisted
      dismembered pyeloplasty can be performed efficiently by the retroperitoneal
      laparoscopic technique. Our surgical outcomes are comparable to previously
      published laparoscopic and transperitoneal robotic-assisted dismembered
      pyeloplasty series in adults with excellent clinical and radiologic success
      rates.

PMID- 18811573
TI  - Effect of retroperitoneal laparoscopic radical nephrectomy of renal carcinoma
      (nephroma) on perioperative cell immunity.
AB  - PURPOSE: To determine perioperative cellular immune responses to retroperitoneal
      laparoscopic radical nephrectomy by comparing them with those to open radical
      nephrectomy. METHODS: Fifty-two patients with renal cell carcinoma were equally
      randomized into two groups: laparoscopic nephrectomy group (LN group) and open
      nephrectomy group (ON group) to compare differences in cellular immunofunction.
      The peripheral blood lymphocyte subpopulations (CD3, CD4, CD8, CD25, CD69,
      Fas/FasL) were detected with flow cytometry. All tests were performed before
      operation and at 1, 3, and 5 days after operation. All data were assessed by
      repeated measurement and variance analysis t test and chi(2) tests. RESULTS: CD3
      and CD4 levels in the ON group decreased significantly 1 day and 3 days after
      operation but recovered on day 5; CD8 level (5 days after operation) in the ON
      group was significantly higher than that in the LN group. CD25 level (3 days
      after operation) in the LN group was significantly higher than that in the ON
      group. CD69 level 3 days after operation in the ON group was significantly higher
      than that in the LN group. In the ON group, CD69 increased markedly 3 days after
      operation. FasL level (in both the LN and ON groups) was higher than the normal
      reference; Fas and FasL in the ON group were higher than those in the LN group.
      CONCLUSION: The perioperative immune response is less obvious after a
      laparoscopic procedure compared with a conventional approach in patients with
      renal cell carcinoma.

PMID- 18811574
TI  - Robotic equipment malfunction during robotic prostatectomy: a multi-institutional
      study.
AB  - PURPOSE: Robotic-assisted laparoscopic prostatectomy (RALP) is growing in
      popularity as a treatment option for prostate cancer. As a new technology, little
      is known regarding the reliability of the da Vinci robotic system. Intraoperative
      robotic equipment malfunction may force the surgeon to convert the procedure to
      an open or pure laparoscopic procedure, or possibly even abort the procedure. We
      report the first large-scale, multi-institutional review of robotic equipment
      malfunction. MATERIALS AND METHODS: A questionnaire was designed to evaluate the
      rate of perioperative robotic malfunction during RALP. High-volume, experienced
      surgeons were asked to complete this evaluation based on the analysis of their
      data. Questions included the overall number of RALPs performed, the number of
      equipment malfunctions, the number of procedures that had to be converted or
      aborted, and the part of the robotic system that malfunctioned. RESULTS: Eleven
      institutions participated in the study with a median surgeon volume of 700 cases,
      accounting for a total case volume of 8240. Critical failure occurred in 34 cases
      (0.4%) leading to the cancellation of 24 cases prior to the procedure, and the
      conversion to two laparoscopic and eight open procedures. The most common
      components of the robot to malfunction were the arms and optical system.
      CONCLUSIONS: Critical robotic equipment malfunction is extremely rare in
      institutions that perform high volumes of RALPs, with a nonrecoverable
      malfunction rate of only 0.4%.

PMID- 18811575
TI  - Shockwave lithotripsy and endourological management of urinary calculi in
      children: a single-center 10-year experience.
AB  - PURPOSE: Shock wave lithotripsy (SWL) and endourological techniques
      revolutionized the management of pediatric urolithiasis. We sought to assess the
      impact of new technology and local practice in the treatment of pediatric
      urolithiasis during a 10-year period. MATERIALS AND METHODS: Between 1997 and
      2006, 125 children (90 boys and 35 girls), aged 18 months to 15 years, were
      managed in our department for urolithiasis. Stone localization, stone
      composition, presence of anatomic abnormalities, and treatment modality were
      evaluated retrospectively. RESULTS: In 102 children, the stone was located in
      renal pelvis (0.5-45-mm diameter), in eight in the renal pelvis and one in the
      calyx; three had staghorn calculi; and 12 had ureteral stone (4-12-mm diameter).
      Ninety-three of 125 children underwent a total of 108 SWL sessions. Stone size
      ranged from 0.5 to 35 mm. The stone-free rates were 86%, 92%, and 96% after
      first, second, and third SWL session, respectively. Ureteroscopy was performed in
      12/125 children, and 10/12 (83.5%) were rendered stone free. Nine of 125 children
      underwent percutaneous nephrolithotomy, and four of nine were stone free (44.5%),
      although five of the nine children (55.5%) required SWL for residual stone
      fragments. Open surgery was performed as initial procedure in 11 (9%) children.
      In 9 of 11 children, ureteropelvic junction obstruction was corrected
      simultaneously. Open surgery was followed by SWL in 3 of 11 patients. Two of
      three patients with staghorn calculi underwent nephrolithotomy and SWL and one of
      three with cysteinuria was managed with SWL. CONCLUSIONS: SWL and endourological
      techniques are safe and effective in managing urolithiasis in pediatric patients.
      These minimally invasive methods reduced dramatically the cases of open surgery,
      which should be undertaken mainly in coexisting anatomic abnormalities.

PMID- 18811576
TI  - Anatomic predictors of formation of lower caliceal calculi: is it the time for
      three-dimensional computed tomography urography?
AB  - OBJECTIVE: To evaluate the various anatomic factors, using computed tomography
      urography (CTU), that predispose to a lower-pole kidney stone formation on one
      side compared with the other. MATERIALS AND METHODS: The study included 51
      patients with a solitary lower-pole stone. Lower-pole infundibulopelvic angle
      (IPA), infundibular width (IW), infundibular length (IL), caliceal volume (CV),
      and number of minor calices of the affected lower calyx and normal contralateral
      kidney were measured based on CTU. The IPA was measured according to the methods
      of Sampaio and Elbahnasy. A comparison was made using multivariate analysis to
      determine whether any of these measurements predisposed one side to form stones.
      RESULTS: The mean IPA was 80.9 degrees (Sampaio), and 52.3 degrees (Elbahnasy) on
      the affected kidney and 87.5 degrees (P = 0.39) and 54 degrees (P = 0.36) on the
      normal side. The mean IW was 2.6 mm on affected side and 3.15 mm on the normal
      side (P = 0.03). The mean IL was 19.7 mm and 15.3 mm (P < 0.001) on the affected
      and normal kidneys, respectively. Mean CV was 1123 mm(3) on affected side and 286
      mm(3) on the normal side (P < 0.001). The mean number of minor calices was
      comparable (n = 3) on both sides with no statistical significance. Using
      multivariate analysis, only caliceal volume and IW sustained their significance
      in the final model. CONCLUSIONS: CTU is a very useful imaging modality in the
      diagnosis of intrarenal anatomic variation. Larger caliceal volume and narrower
      IW are associated with stone formation in lower calyx.

PMID- 18811577
TI  - Anaphylaxis following cystoscopy with equipment sterilized with Cidex OPA (ortho
      phthalaldehyde): a review of two cases.
AB  - PURPOSE: Ortho-phthalaldehyde (Cidex OPA) is a commonly used solution for rapid
      sterilization of flexible endoscopic equipment. We report two cases of
      anaphylaxis following cystoscopy with endoscopes sterilized with this agent. Only
      a handful of such reactions have been reported in the published literature, the
      majority of which are in the bladder cancer population undergoing surveillance
      cystoscopy. PATIENTS AND METHODS: We reviewed the clinical presentation of two
      cases of anaphylaxis following flexible cystoscopy with instruments sterilized
      with ortho-phthalaldehyde. We further describe their subsequent evaluation by an
      allergy and immunology specialist who performed skin testing to confirm a
      suspected ortho-phthalaldehyde allergy. RESULTS: Both patients were skin test
      positive to ortho-phthalaldehyde antigen. As a result, sterilization techniques
      for our flexible endoscopes has been altered. To date, no further anaphylactic
      reactions have occurred in our bladder cancer patients, including the two cases
      presented herein following subsequent cystoscopic evaluations. CONCLUSIONS: Ortho
      phthalaldehyde-sterilized cystoscopes have been associated with anaphylactic
      reactions in a small number of patients who have undergone repeated cystoscopy.
      The manufacturer has already made recommendations to avoid this agent in bladder
      cancer patients. It may be prudent to extend this practice to other populations
      undergoing repeat cystoscopy.

PMID- 18811584
TI  - Severe tuberculosis induces unbalanced up-regulation of gene networks and
      overexpression of IL-22, MIP-1alpha, CCL27, IP-10, CCR4, CCR5, CXCR3, PD1, PDL2,
      IL-3, IFN-beta, TIM1, and TLR2 but low antigen-specific cellular responses.
AB  - The immune mechanisms by which early host-mycobacterium interaction leads to the
      development of severe tuberculosis (TB) remain poorly characterized in humans.
      Here, we demonstrate that severe TB in juvenile rhesus monkeys down-regulated
      many genes in the blood but up-regulated selected genes constituting gene
      networks of Th17 and Th1 responses, T cell activation and migration, and
      inflammation and chemoattractants in the pulmonary and lymphoid compartments.
      Overexpression (450-2740-fold) of 13 genes encoding inflammatory cytokines and
      receptors (IL-22, CCL27, MIP-1alpha, IP-10, CCR4, CCR5, and CXCR3), immune
      dysfunctional receptors and ligands (PD1 and PDL2), and immune activation
      elements (IL-3, IFN-beta, TIM1, and TLR2) was seen in tissues, with low antigen
      specific cellular responses. Thus, severe TB in macaques features unbalanced up
      regulation of immune-gene networks without proportional increases in antigen
      specific cellular responses.

PMID- 18811586
TI  - Monitors and civility, followups, nystagmus from guitar hero! Pediatric
      cataracts: review; monocular elevation deficiency strabismus.

PMID- 18811585
TI  - Evaluation of the clinical significance of homB, a novel candidate marker of
      Helicobacter pylori strains associated with peptic ulcer disease.
AB  - BACKGROUND: homB codes for a putative Helicobacter pylori outer membrane protein
      and has previously been associated with peptic ulcer disease (PUD) in children.
      METHODS: A total of 190 H. pylori strains isolated from children and adults were
      studied to evaluate the clinical importance of the homB gene. In vitro
      experiments were performed to identify HomB mechanisms of bacterial
      pathogenicity. RESULTS: Characterization of the isolates demonstrated that homB
      was significantly associated with PUD in 86 children (odds ratio [OR], 7.64 [95%
      confidence interval {CI}, 2.65-22.05]) and in 32 adults < or =40 years of age
      (OR, 11.25 [95% CI, 1.86-68.13]). homB was correlated with the presence of cagA,
      babA2, vacAs1, hopQI, and oipA "on" genotype (P< .001) The HomB protein was found
      to be expressed in the H. pylori outer membrane and was noted to be antigenic in
      humans. H. pylori homB knockout mutant strains presented reduced ability to
      induce interleukin-8 secretion from human gastric epithelial cells, as well as
      reduced capacity to bind to these cells. Both of these functions correlated with
      the number of homB copies present in a strain. CONCLUSION: homB can be considered
      a comarker of H. pylori strains associated with PUD. Moreover, results strongly
      suggest that HomB is involved in the inflammatory response and in H. pylori
      adherence, constituting a novel putative virulence factor.

PMID- 18811587
TI  - Protracted micro-nystagmus induced by video game play in a patient with mild
      ocular albinism.

PMID- 18811588
TI  - Cataract update 2008: all you need to know about your pediatric cataract
      patients.

PMID- 18811589
TI  - Monocular elevation deficiency with contralateral superior oblique muscle tendon
      laxity.
AB  - INTRODUCTION: Monocular elevation deficiency with a tight ipsilateral inferior
      rectus muscle and fixation preference for the contralateral eye is a well
      recognized entity in strabismus. Most descriptions of the condition, however, do
      not document oblique muscle forced duction testing in the contralateral eye. The
      purpose of this report is to raise awareness that monocular elevation deficiency
      can be associated with, and may be secondary to, a floppy (lax) superior oblique
      muscle tendon in the contralateral fixating eye. METHODS: Retrospective case
      series. RESULTS: All 4 patients were previously diagnosed with congenital
      monocular elevation deficiency. All had variable head tilt towards the hypotopic
      eye, pseudoptosis with mild elevation limitation in that eye, and bilateral
      fundus excyclotorsion. In addition to inferior rectus muscle restriction in the
      hypotropic eye, forced duction testing was significant for contralateral superior
      oblique muscle tendon laxity. CONCLUSIONS: Fixation preference for the eye with
      lax superior oblique muscle tendon may have led to a tight inferior rectus muscle
      in the non preferred eye. However, a congenital association between tight
      inferior rectus muscle and a lax superior oblique muscle tendon in the other eye
      cannot be ruled out. Patients diagnosed with monocular elevation deficiency
      should have careful attention to forced duction testing of the contralateral
      superior oblique muscle tendon.

PMID- 18811590
TI  - Autoactivation of human ADAM8: a novel pre-processing step is required for
      catalytic activity.
AB  - Members of the ADAM (a disintegrin and metalloproteinase) family of proteins
      possess a multidomain architecture which permits functionalities as adhesion
      molecules, signalling intermediates and proteolytic enzymes. ADAM8 is found on
      immune cells and is induced by multiple pro-inflammatory stimuli suggesting a
      role in inflammation. Here we describe an activation mechanism for recombinant
      human ADAM8 that is independent from classical PC (pro-protein convertase)
      mediated activation. N-terminal sequencing revealed that, unlike other ADAMs,
      ADAM8 undergoes pre-processing at Glu(158), which fractures the Pro (pro-segment)
      domain before terminal activation takes place to remove the putative cysteine
      switch (Cys(167)). ADAM8 lacking the DIS (disintegrin) and/or CR (cysteine-rich)
      and EGF (epidermal growth factor) domains displayed impaired ability to complete
      this event. Thus pre-processing of the Pro-domain is co-ordinated by DIS and
      CR/EGF domains. Furthermore, by placing an EK (enterokinase) recognition motif
      between the Pro- and catalytic domains of multiple constructs, we were able to
      artificially remove the pro-segment prior to pre-processing. In the absence of
      pre-processing of the Pro-domain a marked decrease in specific activity was
      observed with the autoactivated enzyme, suggesting that the Pro-domain continued
      to associate and inhibit active enzyme. Thus, pre-processing of the Pro-domain of
      human ADAM8 is important for enzyme maturation by preventing re-association of
      the pro-segment with the catalytic domain. Given the observed necessity of DIS
      and CR/EGF for pre-processing, we conclude that these domains are crucial for the
      proper activation and maturation of human ADAM8.

PMID- 18811591
TI  - Cln6 mutants associated with neuronal ceroid lipofuscinosis are degraded in a
      proteasome-dependent manner.
AB  - NCLs (neuronal ceroid lipofuscinoses), a group of inherited neurodegenerative
      lysosomal storage diseases that predominantly affect children, are the result of
      autosomal recessive mutations within one of the nine cln genes. The wild-type cln
      gene products are composed of membrane and soluble proteins that localize to the
      lysosome or the ER (endoplasmic reticulum). However, the destiny of the Cln
      variants has not been fully characterized. To explore a possible link between ER
      quality control and processing of Cln mutants, we investigated the fate of two
      NCL-related Cln6 mutants found in patient samples (Cln6(G123D) and Cln6(M241T))
      in neuronal-derived human cells. The point mutations are predicted to be in the
      putative transmembrane domains and most probably generate misfolded membrane
      proteins that are subjected to ER quality control. Consistent with this paradigm,
      both mutants underwent rapid proteasome-mediated degradation and complexed with
      components of the ER extraction apparatus, Derlin-1 and p97. In addition,
      knockdown of SEL1L [sel-1 suppressor of lin-12-like (Caenorhabditis elegans)], a
      member of an E3 ubiquitin ligase complex involved in ER protein extraction,
      rescued significant amounts of Cln6(G123D) and Cln6(M241T) polypeptides. The
      results implicate ER quality control in the instability of the Cln variants that
      probably contributes to the development of NCL.

PMID- 18811593
TI  - Influence of source of phospholipids for APTT-based factor IX assays and
      potential consequences for the diagnosis of mild haemophilia B.

PMID- 18811594
TI  - Endodontic management of badly broken down teeth using the canal projection
      system: two case reports.
AB  - AIM: Teeth that have been weakened by caries and require root canal treatment to
      maintain their functional integrity may present with minimal coronal tooth
      structure and are a challenge for isolation and restoration. The aim of this
      clinical report is to demonstrate the management of badly broken down teeth using
      the Projector Endodontic Instrument Guidance System (PEIGS). SUMMARY: The PEIGS
      is an adjunct to root canal treatment designed to enhance the ease of treatment
      delivery. Use of this system facilitates projection of canal orifices from the
      floor of the pulp chamber to the cavosurface, providing direct visualization of
      and physical access to the projected canals. This report demonstrates the use of
      this novel device for the management of two badly broken down teeth. KEY LEARNING
      POINTS: Use of the endodontic projection system has the following advantages: *
      'Projects' the canal orifice from the floor of the pulp chamber to the
      cavosurface, thereby enhancing visualization and access to the canals. * The
      bonded coronal build up reduces the risk of interappointment crack initiation and
      coronal-radicular fracture of weakened tooth structure. * Permits
      individualization of canals especially when they lie in close proximity to each
      other on the chamber floor. * Isolation may be facilitated by ease of clamp
      retention, rendering many structurally debilitated teeth endodontically
      treatable.

PMID- 18811595
TI  - Endodontic malpractice claims in Denmark 1995-2004.
AB  - AIM: To study the reasons for and outcome of malpractice claims handled by the
      regional and national Danish Dental Complaint Boards (DCB) from 1995 to 2004.
      Specific attention was paid to endodontic claims. Three hypotheses were explored:
      endodontic malpractice claims are frequent, they are mostly due to technical
      shortcomings and male dentists are overrepresented. METHODOLOGY: The reasons for
      the claims were classified and assigned to at least one of 14 categories. Cases
      assigned to the 'endodontic treatment' category were further sub-categorized, and
      reasons for malpractice were examined. An age and gender analysis of dentists and
      complaining patients was performed only on data obtained from the endodontic
      cases. RESULTS: Overall, 3611 malpractice claims were registered. In 43% of the
      cases the dentist was judged to be guilty of malpractice. In the majority of the
      appealed cases the original verdict was affirmed (62.2%) by the national DCB.
      After crown & bridge treatment (23%) endodontic treatment was the next frequent
      malpractice claim (13.7%), in which 'technical complications or incorrect
      treatment' was the most frequent sub-categorization (28.4%). Reasons for
      endodontic malpractice verdicts were related to root filling quality, the use of
      a paraformaldehyde product and instrument fracture. Male dentists were most often
      involved in an endodontic claim, and the majority of complainants were females.
      CONCLUSIONS: Endodontic malpractice claims were relatively common in Denmark.
      Perceived technical shortcomings dominated the patients' complaints concerning
      root canal treatment. Male dentists and female patients were overrepresented
      indicating a gender influence on aspects of the doctor-patient communication
      important for liability claims.

PMID- 18811596
TI  - A preliminary study of the use of peripheral quantitative computed tomography for
      investigating root canal anatomy.
AB  - AIM: To evaluate the use of peripheral quantitative computed tomography (pQCT)
      for qualitative and quantitative analysis of root canal anatomy and for assessing
      the extent of canal enlargement during root canal instrumentation. SUMMARY: The
      volume variation achieved by S1 ProTaper instruments in the coronal third of the
      root canals was analysed using peripheral computed tomography. The tooth was
      scanned in the horizontal plane producing 36 consecutive cross-sectional images.
      All images were the result of 360 projections with a section thickness of 250
      microm, a distance between slices of 0.5 mm and an in-plane pixel size of 70 x 70
      microm. The evaluation was completed before and after S1 ProTaper instrumentation
      (with or without circumferential filing) of one root canal of a freshly extracted
      maxillary first premolar tooth. The acquired images were realigned geometrically
      and processed using a 3D visualization software. pQCT scanning allowed 3D
      reconstruction of the root canal anatomy and the assessment of the extent of
      canal enlargement during root canal instrumentation with lateral displacement of
      canal walls and hence volume change being greater than the coefficient of
      variation. The densitometry evaluation showed uniform density along the root
      canal wall. KEY LEARNING POINTS: * pQCT scanning allowed 3D reconstruction of the
      root canal anatomy and the assessment of the extent of canal enlargement during
      root canal instrumentation. * pQCT shows promise for allowing qualitative and
      quantitative analysis of endodontic procedures.

PMID- 18811597
TI  - Similar expression of through-and-through fluid movement along orthograde apical
      plugs of MTA Bio and white Portland cement.
AB  - AIM: To compare the sealing ability of four hydraulic cements when used as an
      apical plug in teeth with wide-open apices. METHODOLOGY: A sample of 70 maxillary
      central incisors were divided into four groups (n = 15) and a further 10 teeth
      served as controls. An artificial open apex was created in the teeth using Gates
      Glidden drills numbers 6-1 in a crown-down manner until the size 1 bur passed
      through the foramen. A divergent open apex was prepared to a size of 1.24 mm at
      the foramen by retrograde apical transportation using a number 8 (0.60) Profile
      Series 29 0.4 taper instrument inserted to the length of the cutting blade. In
      G1, the open apices were repaired with WMTA Angelus whilst in G2, G3 and G4 MTA
      Bio, Pro-Root MTA and Portland cement was employed respectively. Each root was
      assembled in a hermetic cell to allow the evaluation of fluid filtration. Leakage
      was measured by the movement of an air bubble travelling within a pipette
      connected to the teeth. Measurements of the air bubble movement were made after
      10 min at a constant pressure of 50 cm H(2)O. The Kruskal-Wallis H-test was
      applied to the fluid flow data to detect differences between the experimental
      groups (P < 0.05). RESULTS: Fluid movement occurred in every sample but was
      variable in all the experimental groups, ranging from 0.61 to 2.45 microL min(
      1). There was no significant difference in mean fluid flow between the
      experimental groups (P > 0.05). CONCLUSIONS: Fluid movement through teeth with
      open apices and filled with four hydraulic cements was similar. All cements
      allowed fluid movement.

PMID- 18811598
TI  - The IMPROVE study--a multinational, observational study in type 2 diabetes:
      baseline characteristics from eight national cohorts.
AB  - AIMS: The IMPROVE study is a multinational, open-label, non-randomised, 26-week
      observational study assessing the safety and effectiveness of biphasic insulin
      aspart 30 (BIAsp 30) treatment in type 2 diabetes in routine clinical practice.
      The principal aims of this report were to characterise the baseline population
      and physicians' treatment decisions. METHODS: Patients with type 2 diabetes who
      required insulin and whose physician had decided to initiate BIAsp 30 were
      eligible. At baseline, demographic data and detailed medical histories were
      collected and physicians recorded their reasons for starting BIAsp 30, the
      glycaemic targets set and the regimens chosen. RESULTS: Data from 51,286 patients
      were included in analyses. Baseline glycaemic control was poor in all eight
      countries in the present analysis and in all prestudy treatment groups [no
      therapy, oral antidiabetic drugs (OADs) only, insulin with or without OADs], and
      the rates of vascular complications were high. Although the management of each of
      the three main measures of glycaemic control were key reasons for starting BIAsp
      30, target-setting for postprandial glucose levels was variable. A twice-daily
      regimen was used to start BIAsp 30 therapy for 80% or more of patients.
      CONCLUSIONS: The IMPROVE baseline data reaffirm the global nature of poor
      glycaemic control in type 2 diabetes and echo the concerns that initiation of
      therapy, particularly insulin, is commonly delayed in clinical practice. Although
      postprandial glucose control was a key driver for physicians' choice of BIAsp 30,
      this was not consistently reflected in the targets set.

PMID- 18811599
TI  - Darifenacin treatment for overactive bladder in patients who expressed
      dissatisfaction with prior extended-release antimuscarinic therapy.
AB  - INTRODUCTION AND OBJECTIVE: Patient perception of overactive bladder (OAB)
      treatment outcomes can be a useful indicator of benefit and may help drive
      persistence on treatment, which is known to be poor in OAB. It remains unclear
      whether OAB patients dissatisfied with one antimuscarinic can achieve
      satisfaction with another and supporting data are limited. This study
      investigated patient-reported outcomes and clinical parameters during darifenacin
      treatment in OAB patients who expressed dissatisfaction with prior extended
      release (ER) oxybutynin or tolterodine therapy (administered for >or= 1 week
      within the past year). METHODS: This open-label study was conducted in
      darifenacin-naive OAB patients. Patients received 7.5 mg darifenacin once daily
      with the possibility of up-titrating to 15 mg after 2 weeks, for up to 12 weeks.
      Efficacy parameters included the Patient's Perception of Bladder Condition
      (PPBC), patient satisfaction with treatment, micturition frequency and number of
      urgency and urge urinary incontinence (UUI) episodes. Adverse events (AEs) were
      also recorded. RESULTS: In total, 497 patients were treated (84.1% women).
      Darifenacin treatment resulted in statistically significant improvements in PPBC
      scores, micturition frequency, urgency and UUI episodes from baseline at 12
      weeks. The improvements were similar for patients previously treated with
      oxybutynin ER or tolterodine ER. More than 85% of patients expressed satisfaction
      with darifenacin. As noted in other studies, the most common AEs were dry mouth
      and constipation, but these infrequently resulted in treatment discontinuation,
      which was low overall. CONCLUSIONS: In this study, PPBC score and OAB symptoms
      were significantly improved, and satisfaction was high during treatment with
      darifenacin (7.5/15 mg) in patients who were dissatisfied with the previous
      antimuscarinic treatment.

PMID- 18811600
TI  - Characterization and expression of the odorant-binding protein 7 gene in
      Anopheles stephensi and comparative analysis among five mosquito species.
AB  - Odorant-binding proteins (OBPs) are important molecular players in insect
      olfaction, which has a great influence on the host-seeking behaviour of
      mosquitoes and other disease vectors. The mRNA level of the Anopheles gambiae
      Obp7 gene (Agam-Obp7) is higher in the adult female antennae and is slightly
      reduced in the female heads after blood-feeding. Here we report the cloning,
      sequencing, chromosomal mapping and transcript analysis of Aste-Obp7, the Obp7
      gene from the Asian malaria mosquito Anopheles stephensi. Quantitative reverse
      transcription PCR showed that in adult female mosquitoes, Aste-Obp7 was expressed
      abundantly in the antennae, much less in pooled maxillary palp and proboscis and
      at the lowest level in the legs. The Aste-Obp7 level in female antennae was
      significantly higher than in male antennae and it slightly increased 24 h after a
      bloodmeal. The same pattern held for leg samples as well. The Aste-Obp7 mRNA
      level dropped more than 10-fold in the female maxillary palp and proboscis after
      a bloodmeal, although it was still significantly higher than in the males.
      Together, the above expression profiles suggest that Aste-Obp7 probably functions
      in female olfaction and may possibly be involved in behaviour related to blood
      feeding. We also characterized the Obp7 gene from Anopheles quadriannulatus.
      Comparison among Anopheles Obp7 genes revealed conserved noncoding sequences that
      contain potential regulatory elements. The coding sequence and gene structure of
      Obp7 as well as local synteny of surrounding genes are conserved among the three
      Anopheles species and two divergent mosquitoes, Aedes aegypti and Culex pipiens
      quinquefasciatus. OBP7 protein phylogeny is congruent with the mosquito phylogeny
      and there is evidence of purifying selection acting on the mosquito Obp7 gene.
      Comparative genomics analysis will improve our understanding of the evolution and
      regulation of genes involved in mosquito olfaction.

PMID- 18811601
TI  - Semliki Forest virus strongly reduces mosquito host defence signaling.
AB  - The Alphavirus genus within the Togaviridae family contains several important
      mosquito-borne arboviruses. Other than the antiviral activity of RNAi, relatively
      little is known about alphavirus interactions with insect cell defences. Here we
      show that Semliki Forest virus (SFV) infection of Aedes albopictus-derived U4.4
      mosquito cells reduces cellular gene expression. Activation prior to SFV
      infection of pathways involving STAT/IMD, but not Toll signaling reduced
      subsequent virus gene expression and RNA levels. These pathways are therefore not
      only able to mediate protective responses against bacteria but also arboviruses.
      However, SFV infection of mosquito cells did not result in activation of any of
      these pathways and suppressed their subsequent activation by other stimuli.

PMID- 18811602
TI  - Oral isotretinoin in photoaging: clinical and histopathological evidence of
      efficacy of an off-label indication.
AB  - BACKGROUND: Despite evidences of the beneficial clinical effects of oral
      isotretinoin in the treatment of cutaneous photoaging, scientific evidences are
      still scarce, mainly supported by histopathological and morphometric studies.
      OBJECTIVES: To analyse possible clinical and morphological changes resulting from
      the treatment of photoaging with oral isotretinoin. METHODS: Thirty female
      patients, aged 40 to 55 years, phototypes II to IV, with moderate to severe
      photoaging were randomly assigned to two groups of 15 each. Group I (G I)
      patients were treated with 10 mg of isotretinoin and group II (G II) with 20 mg
      of oral isotretinoin thrice a week for 3 months. Skin biopsies were performed
      before and after the end of therapy, and the various sections were submitted to
      specific staining for collagen and elastic fibres. To analyse the changes,
      morphometric studies were performed, and the results obtained were analysed by
      Student's t-test (paired and non-paired). Clinical results of therapy regarding
      texture, colouring and aspect of the wrinkles were assessed by both physician and
      patient. RESULTS: The increase in the amount of collagen fibres was statistically
      significant with both dosage regimens (mean, 37.8%, increasing to 44.4%; P =
      0.029 with the 10-mg dosage; and mean, 36.6%, increasing to 41.9%; P = 0.01 with
      the 20-mg dosage). A pattern pointing toward a decrease in the number of elastic
      fibres was found (mean, 15.3-12%; P = 0.014 with the 10-mg dosage; mean, 15.5
      14%; P = 0.125 with the 20-mg dosage). Additionally, there was improvement in the
      general aspect of the skin, regarding texture, wrinkles depth and skin
      coloration. LIMITATIONS: Despite ethical considerations, a lack of a control
      group using placebo may render the results less accurate. CONCLUSION: Low dosages
      of oral isotretinoin seem to be an effective therapeutic option for cutaneous
      photoaging.

PMID- 18811603
TI  - Optical coherence tomography imaging of bullous diseases.
AB  - BACKGROUND: Optical coherence tomography (OCT) is a non-invasive optical imaging
      technique with a micrometer resolution that may potentially offer real-time
      bedside imaging of sufficient detail to allow for morphological discrimination
      between different types of bullae. OBJECTIVE: To explore the potential of OCT in
      bullous skin disorders by looking at a set of patients with skin blisters of
      known origin and study the OCT images for possible hallmarks of the blistering
      level. MATERIALS AND METHODS: OCT provides cross-sectional, tomographic images of
      the skin. A consecutive series of patients were recruited and their lesions
      imaged by OCT: 3 patients with bullous pemphigoid (BP), 1 patient with extensive
      bullae following burns, 1 patient with pemphigus, 1 patient with subcorneal
      pustular dermatosis, and a patient with Dariers disease. The latter two were
      included due to similarity to pemphigus with respect to the level of defect cell
      adhesion. RESULTS: In OCT images, BP bullae are easily depicted as dark, ovoid to
      round well-demarquated areas, and BP bulla morphology is clearly different from
      the burn blisters and the pemphigus-like disease with respect to the blistering
      level. DISCUSSION: Differentiation of epidermal and subepidermal blisters is
      demonstrated using OCT. The variation within pemphigoid lesions and pemphigus
      like diseases is however too subtle to allow for differential diagnosis; this may
      be ascribed to limited resolution. Enhanced resolution of OCT may overcome this
      obstacle.

PMID- 18811604
TI  - Fatigue predicts mortality in older adults.
AB  - OBJECTIVES: To determine the association between fatigue and survival over 10
      years in a population of older community-dwelling primary care patients. DESIGN:
      Prospective cohort study. SETTING: Medicare health maintenance organization and
      Veterans Affairs primary care programs. PARTICIPANTS: Older primary care patients
      (N=492). MEASUREMENTS: Fatigue, operationalized as feeling tired most of the
      time, was assessed at baseline. Mortality was ascertained from the National Death
      Index. Covariates included demographics, comorbidity, cognitive function,
      depressive symptoms, body mass index, self-rated health, functional status, and
      gait speed. RESULTS: Mortality rates at 10 years were 59% (123/210) for older
      adults with fatigue, versus 38% (106/282) for those without fatigue (P<.001).
      After adjustment for multiple potential confounders, participants who were tired
      at baseline had a greater risk of death than those who were not (hazard
      ratio=1.44, 95% confidence interval=1.08-1.93). CONCLUSION: A single simple
      question "Do you feel tired most of the time?" identifies older adults with a
      higher risk of mortality. Further research is needed to identify and characterize
      the underlying mechanisms of fatigue, to develop and test specific treatments,
      and to determine whether improvement leads to decreased morbidity and mortality.

PMID- 18811605
TI  - Depression and disability: comparisons with common physical conditions in the
      Ibadan study of aging.
AB  - OBJECTIVES: To compare the effects of depression and chronic physical conditions
      on disability in elderly persons. SETTING: Yoruba-speaking areas of Nigeria.
      DESIGN: Interviews. PATICIPANTS: Community-dwelling persons aged 65 and older.
      METHOD: Face-to-face interviews were conducted with a representative sample of
      community-dwelling persons aged 65 and older (N=2,152) in the Yoruba-speaking
      areas of Nigeria (representing approximately 22% of the national population).
      Major depressive disorder (MDD) was assessed using the World Health Organization
      Composite International Diagnostic Interview. Chronic pain and medical disorders
      were assessed using self-report. Disorder-specific disability was evaluated using
      the Sheehan Disability Scale (SDS). RESULTS: MDD was highly comorbid with each of
      the medical conditions (odds ratio range 1.3-2.0). A higher proportion of persons
      with MDD (47.2%) were rated severely disabled globally than those with arthritis
      (20.6%), chronic spinal pain (24.2%), or high blood pressure (25.0%). Subjects
      with MDD were also more likely to be severely disabled in three of the four
      domains of the SDS. In pair-wise comparisons, persons with MDD had significantly
      higher levels of disability than those with any of the disorders, with
      differences in mean scores ranging between -3.74 and -27.50. CONCLUSION: To
      reduce the public health burden of depression, its prevention and treatment
      require more clinical and research attention than currently given by developing
      countries.

PMID- 18811606
TI  - Risk factors for fracture following a fall among older people in residential care
      facilities in Australia.
AB  - OBJECTIVES: To investigate which factors best predict whether a fall will result
      in a fracture. DESIGN: Prospective cohort. SETTING: Residential care facilities.
      PARTICIPANTS: One thousand three hundred forty-two older men and women (mean age
      86.0) who had a fall. MEASUREMENTS: Clinical risk factors and bone fragility by
      calcaneus broadband ultrasound attenuation (BUA) were assessed at baseline, and
      falls and fall-related fractures were recorded for up to 2 years. All fractures
      were validated using X-ray reports. RESULTS: During a median follow-up of 1.97
      years, 6,646 falls resulted in 308 fractures. Fracture rates were 6.7, 4.8, and
      3.1 per 100 falls for BUA in the lowest (10.5-39.7 dB/MHz), middle (39.8-58.9
      dB/MHz), and highest (>/=58.9dB/MHz) tertiles, respectively. In multivariate
      analysis, the odds ratio for any fracture was 1.17 (95% confidence interval=1.08
      1.27; P<.001) for every 10-dB/MHz reduction in BUA. Other significant risk
      factors in the model were lower weight, longer leg length, better balance, no
      severe cognitive impairment, intermediate care residence, lack of a history of
      falls in the previous year, and a history of fracture since age 50. For hip
      fracture, the only significant risk factors were lower weight, longer leg length,
      intermediate care residence, and lack of falls history. CONCLUSION: Important
      risk factors for whether a fracture occurs immediately after a fall include
      direct measures of bone fragility and a number of anthropometric and clinical
      factors that may increase or attenuate the mechanical impact of a fall. By
      identifying those at highest risk of fracture after a fall, these findings should
      have important implications for fracture prevention strategies.

PMID- 18811607
TI  - Tests of muscle strength and physical function: reliability and discrimination of
      performance in younger and older men and older men with mobility limitations.
AB  - OBJECTIVES: To compare the reliability of muscle strength and physical function
      measures in younger and older men. DESIGN: Cross-sectional. SETTING: Academic
      research center. PARTICIPANTS: Thirty younger men, 31 older men, and 39 older men
      with mobility limitations. MEASUREMENTS: Test-retest measures of one repetition
      maximum (1 RM), unloaded and loaded 50-m walk and stair climb, and a lift-and
      lower task. Reliability was assessed using intraclass correlation (ICC) analysis
      and the Bland-Altman method. RESULTS: Leg and chest press 1 RM measures
      identified significant differences between the groups, exhibited excellent test
      retest reliability in younger men, older men, and older men with mobility
      limitations (ICCs=0.946-0.994) and minimal bias between Trials 1 and 2 (Bland
      Altman=improvement of 21.1 and 1.1 N for leg and chest press, respectively). Test
      retest measures of the time to walk 50 m and climb 12 steps also demonstrated
      excellent agreement (ICCs=0.980-0.988 and 0.942-992, respectively) and minimal
      bias (Bland-Altman=0.755-1.007 and 0.141-0.361 seconds faster, respectively).
      When a subject repeated these measures carrying a modest load, ICCs remained
      greater than 0.940, bias was similar, and the tests better discriminated between
      the groups. The lift-and-lower measure demonstrated excellent agreement
      (ICCs=0.925-0.947) and minimal bias (1.4-2.9 more shelves) and revealed
      significant differences between groups. CONCLUSION: Measures of muscle strength
      and physical function can be performed in younger men, older men, and older men
      with mobility limitations with high reliability. In future clinical trials, more
      challenging measures of performance may better discriminate between higher
      functioning study participants.

PMID- 18811608
TI  - Anemia is associated with the progression of white matter disease in older adults
      with high blood pressure: the cardiovascular health study.
AB  - OBJECTIVES: To investigate whether anemia predicts worsening white matter
      hyperintensities (WMHs) in older community-dwellers. DESIGN: Prospective cohort
      study. SETTING: Older community-dwellers. PARTICIPANTS: One thousand eight
      hundred forty-six Cardiovascular Health Study (CHS) participants (mean age 73.7
      +/- 4.4, 41% male, 15.6% African American). MEASUREMENTS: Participants had
      hemoglobin measured and brain magnetic resonance imaging (MRI) in 1992/93 and a
      second brain MRI in 1997/98. Anemia was defined according to World Health
      Organization criteria (hemoglobin <12 g/dL in women and <13 g/dL in men).
      Worsening WMHs were determined according to standardized side-by-side readings.
      RESULTS: After 5 years, WMHs worsened in 517 participants (28%). Progression was
      not associated with anemia in the whole sample, in sex or race strata, or in
      other prespecified subgroups (participants with renal dysfunction or diabetes
      mellitus), except in participants with high blood pressure (>or=140/90 mmHg). Of
      the 678 participants with high blood pressure, those with anemia (10.5%) had a
      1.79 times greater risk of WMHs worsening (95% confidence interval=1.06-2.98; P
      for interaction between anemia and high blood pressure=.01) independent of
      demographics, baseline WMHs, cardiovascular risk factors and comorbidities,
      medications, renal function, inflammation, and incident stroke (logistic
      regression models). There was no greater risk in participants with anemia with
      normal blood pressure. CONCLUSION: Anemia may contribute to worsening of WMHs in
      older adults with high blood pressure.

PMID- 18811609
TI  - Centenarian offspring: start healthier and stay healthier.
AB  - OBJECTIVES: To assess the relative incidence of age-related diseases in a group
      of centenarian offspring who have thus far been considered to be predisposed to
      "healthy" aging. DESIGN: Longitudinal study. SETTING: Nationwide sample.
      PARTICIPANTS: Four hundred forty centenarian offspring and 192 referent cohort
      subjects who met inclusion criteria of having initial and follow-up health
      questionnaire data available. Median age of both cohorts was 72 at the initial
      health questionnaire. MEASUREMENTS: Initial health questionnaires were collected
      from 1997 to 2006. Follow-up questionnaires were collected from 2004 to 2007. The
      mean period of follow-up was 3.5+/-1.7 years for the centenarian offspring and
      3.9+/-2.2 years for the referent cohort. RESULTS: During the follow-up period,
      centenarian offspring had a 78% lower risk of myocardial infarction (P<.04), 83%
      lower risk of stroke (P<.004), and 86% lower risk of developing diabetes mellitus
      (P<.005) than the referent cohort. There were no significant differences in new
      onset of other age-related diseases. Additionally, centenarian offspring were 81%
      less likely to die (P<.01) than the referent cohort during the follow-up.
      CONCLUSION: These findings suggest that centenarian offspring retain some
      important cardiovascular advantages over time over similarly aged referent cohort
      subjects. These findings reinforce the notion that there may be physiological
      reasons that longevity runs in families and that centenarian offspring are more
      likely to age in better cardiovascular health and with a lower mortality than
      their peers.

PMID- 18811610
TI  - Lower systolic blood pressure is associated with greater mortality in people aged
      85 and older.
AB  - OBJECTIVES: To investigate the association between blood pressure and mortality
      in very old people. DESIGN: Population-based cohort study. SETTING: County of
      Vasterbotten, Sweden. PARTICIPANTS: Half of all subjects aged 85 and all of those
      aged 90 and 95 and older (N=348) in one urban and five rural municipalities in
      the north of Sweden. MEASUREMENTS: Among others, supine blood pressure, Mini
      Mental State Examination, Barthel Index of activities of daily living, Mini
      Nutritional Assessment, and body mass index. Information on diagnoses,
      medications, and 4-year mortality was collected. Associations between blood
      pressure and mortality were investigated using Cox regression analyses,
      controlling for a number of diagnoses and health factors. RESULTS: Baseline
      systolic blood pressure (SBP), diastolic blood pressure, and pulse pressure were
      all inversely associated with mortality within 4 years according to univariate
      analysis. SBP was the strongest predictor. In Cox regression analyses, low SBP
      (<or=120 mmHg) correlated with greater 4-year all-cause mortality alone and when
      controlling for health status. This connection persisted after exclusion of
      deaths within the first year. There was a tendency toward a U-shaped mortality
      curve for the adjusted model, with SBP of 164.2 mmHg (95% confidence
      interval=154.1-183.8 mmHg) being associated with the lowest mortality.
      CONCLUSION: Lower SBP seems to be associated with greater mortality in people
      aged 85 and older, irrespective of health status. There are indications of a U
      shaped correlation between SBP and mortality, and the optimal SBP for this age
      group could be above 140 mmHg.

PMID- 18811611
TI  - Relationship between frailty and cognitive decline in older Mexican Americans.
AB  - OBJECTIVES: To examine the association between frailty status and change in
      cognitive function over time in older Mexican Americans. DESIGN: Data used were
      from the Hispanic Established Population for the Epidemiological Study of the
      Elderly. SETTING: Five southwestern states: Texas, New Mexico, Colorado, Arizona,
      and California. PARTICIPANTS: One thousand three hundred seventy
      noninstitutionalized Mexican-American men and women aged 65 and older with a Mini
      Mental State Examination (MMSE) score of 21 or higher at baseline (1995/96).
      MEASUREMENTS: Frailty, defined as three or more of the following components:
      unintentional weight loss of more than 10 pounds, weakness (lowest 20% in grip
      strength), self-reported exhaustion, slow walking speed (lowest 20% in 16-foot
      walk time in seconds), and low physical activity level (lowest 20% on Physical
      Activity Scale for the Elderly score). Information about sociodemographic
      factors, MMSE score, medical conditions (stroke, heart attack, diabetes mellitus,
      arthritis, cancer, and hypertension), depressive symptoms, and visual impairment
      was obtained. RESULTS: Of the 1,370 subjects, 684 (49.9%) were not frail, 626
      (45.7%) were prefrail (1-2 components), and 60 (4.4%) were frail (>/=3
      components) in 1995/96. Using general linear mixed models, it was found that
      frail subjects had greater cognitive decline over 10 years than not frail
      subjects (estimate=-0.67, standard error=0.13; P<.001). This association remained
      statistically significant after controlling for potential confounding factors.
      CONCLUSION: Frail status in older Mexican Americans with MMSE scores of 21 or
      higher at baseline is an independent predictor of MMSE score decline over a 10
      year period. Future research is needed to establish pathophysiological components
      that can clarify the relationship between frailty and cognitive decline.

PMID- 18811612
TI  - Cognitive status and physical function in older african americans.
AB  - OBJECTIVES: To investigate the relationship between global cognition, three
      specific domains of cognition, and lower extremity function in community-dwelling
      elderly African Americans (AAs) from two community settings. DESIGN: Cross
      sectional study. SETTING: Community. PARTICIPANTS: Ninety-six AA men and women
      aged 60 and older from two community settings, enrolled in the Boosting Minority
      Involvement (BMI) study, a community-based cohort study designed to increase
      research participation of older low-income AAs. MEASUREMENTS: Physical
      performance was assessed using Short Physical Performance Battery score, which is
      composed of three timed tests: a 4-m walking task, static balance assessment, and
      a chair stand test. The Bushke Memory Impairment Screen (MIS) and Mini-Mental
      State Examination were used to assess global memory and global cognition,
      respectively. For domain-specific performance, three z-score composite scores
      (attention, verbal memory, and executive function) were developed using the
      Computer-based Assessment of Mild Cognitive Impairment. RESULTS: All domains of
      cognition were significant predictors of lower extremity function except for
      verbal memory. Executive function and MIS were the best predictors of lower
      extremity function in adjusted models. Participants with poor executive function
      were more than four times as likely to have poorer lower extremity function (odds
      ratio=4.96, 95% confidence interval=1.07-23.0). CONCLUSION: Global memory and
      executive function were the best predictors of lower extremity function in a
      sample of community-dwelling AA adults. Deficits in lower extremity function may
      depend on multifaceted higher executive function control processes.

PMID- 18811613
TI  - A manual of guidelines to score the modified cumulative illness rating scale and
      its validation in acute hospitalized elderly patients.
AB  - OBJECTIVES: To update previous guidelines to score the Cumulative Illness Rating
      Scale (CIRS) and test their usefulness in hospitalized elderly patients. DESIGN:
      The CIRS was scored retrospectively in a cohort of elderly patients followed for
      18 months. SETTING: An acute internal medicine ward in an academic tertiary care
      hospital. PARTICIPANTS: Three hundred eighty-seven patients aged 65 and older.
      MEASUREMENTS: The CIRS was retrospectively scored for the enrolled patients.
      Intrarater and interrater reliability were calculated. Two illness severity
      indices (total score (TSC) and severity (SV)) and one comorbidity index (CM) were
      obtained. Clinical features and comprehensive geriatric assessment (CGA)
      variables were also used. All patients underwent an 18-month follow-up for
      mortality and rehospitalization. RESULTS: Intrarater and interrater reliability
      of the CIRS scored following the guidelines was good (intraclass correlation
      coefficients of 0.83 and 0.81, respectively). The TSC, SV, and CM correlated with
      clinical features (laboratory values, medication usage, and length of in-hospital
      stay) and CGA variables (cognitive impairment, depression and disability). All
      three indices were able to predict 18-month mortality and rehospitalization
      rates. CONCLUSION: This study confirmed the validity of the CIRS as an indicator
      of health status and demonstrated its ability to predict 18-month mortality and
      rehospitalization in hospitalized elderly patients. The availability of detailed
      guidelines for scoring the CIRS can improve its usefulness and facilitate more
      widespread use for research and clinical aims.

PMID- 18811614
TI  - Are medical students socially exclusive? A comparison with economics students.
AB  - CONTEXT: Medical students have long been perceived as socially segregated from
      other students. However, the evidence for this is mainly anecdotal. This study
      investigates this issue by comparing medical students with economics students.
      METHODS: Questionnaires measuring objective and subjective social life patterns
      were completed by 149 medical and 149 economics students at a campus-based
      university in the UK. RESULTS: Medical students drew significantly more of their
      close friends and housemates from among students on the same course than
      economics students. Significantly more medical than economics students had a
      partner on the same course, participated in departmental sports clubs and
      societies, and felt separated from the rest of university life. Commonly reported
      reasons for this separation among medical students were high workloads, that the
      medical school was located outside the main campus, and high numbers of contact
      hours, some of which took place at sites outside the university. DISCUSSION:
      Medical students are more socially exclusive than economics students, which may
      lead to 'in-group' attitudes and behaviours. This is educationally important and
      may affect their future professionalism. Universities should be aware of the
      issues involved when planning curricula, timetables, welfare initiatives and
      campus design. Prospective medical students should be informed of the social
      consequences of studying medicine.

PMID- 18811615
TI  - Arbuscular mycorrhizal fungi can transfer substantial amounts of nitrogen to
      their host plant from organic material.
AB  - Nitrogen (N) capture by arbuscular mycorrhizal (AM) fungi from organic material
      is a recently discovered phenomenon. This study investigated the ability of two
      Glomus species to transfer N from organic material to host plants and examined
      whether the ability to capture N is related to fungal hyphal growth. Experimental
      microcosms had two compartments; these contained either a single plant of
      Plantago lanceolata inoculated with Glomus hoi or Glomus intraradices, or a patch
      of dried shoot material labelled with (15)N and (13)carbon (C). In one treatment,
      hyphae, but not roots, were allowed access to the patch; in the other treatment,
      access by both hyphae and roots was prevented. When allowed, fungi proliferated
      in the patch and captured N but not C, although G. intraradices transferred more
      N than G. hoi to the plant. Plants colonized with G. intraradices had a higher
      concentration of N than controls. Up to one-third of the patch N was captured by
      the AM fungi and transferred to the plant, while c. 20% of plant N may have been
      patch derived. These findings indicate that uptake from organic N could be
      important in AM symbiosis for both plant and fungal partners and that some AM
      fungi may acquire inorganic N from organic sources.

PMID- 18811616
TI  - Acclimation of respiratory temperature responses in northern and southern
      populations of Pinus banksiana.
AB  - Temperature acclimation of respiration may contribute to climatic adaptation and
      thus differ among populations from contrasting climates. Short-term temperature
      responses of foliar dark respiration were measured in 33-yr-old trees of jack
      pine (Pinus banksiana) in eight populations of wide-ranging origin (44-55 degrees
      N) grown in a common garden at 46.7 degrees N. It was tested whether seasonal
      adjustments in respiration and population differences in this regard resulted
      from changes in base respiration rate at 5 degrees C (R(5)) or Q(10) (temperature
      sensitivity) and covaried with nitrogen and soluble sugars. In all populations,
      acclimation was manifest primarily through shifts in R(5) rather than altered
      Q(10). R(5) was higher in cooler periods in late autumn and winter and lower in
      spring and summer, inversely tracking variation in ambient air temperature.
      Overall, R(5) covaried with sugars and not with nitrogen. Although acclimation
      was comparable among all populations, the observed seasonal ranges in R(5) and
      Q(10) were greater in populations originating from warmer than from colder sites.
      Population differences in respiratory traits appeared associated with autumnal
      cold hardening. Common patterns of respiratory temperature acclimation among
      biogeographically diverse populations provide a basis for predicting respiratory
      carbon fluxes in a wide-ranging species.

PMID- 18811617
TI  - A functional genomics resource for Brassica napus: development of an EMS
      mutagenized population and discovery of FAE1 point mutations by TILLING.
AB  - Two ethylmethanesulfonate (EMS) mutant populations of the semi-winter rapeseed
      cv. Ningyou7 were constructed with high mutant load, to provide a TILLING
      platform for functional genomics in Brassica napus, and for introduction of novel
      allelic variation in rapeseed breeding. Forward genetic screening of mutants from
      the M2 populations resulted in identification of a large number of novel
      phenotypes. Reverse genetic screening focused on the potentially multi-paralogous
      gene FAE1 (fatty acid elongase1), which controls seed erucic acid synthesis in
      rapeseed. A B. napus BAC library was screened, and loci in a reference mapping
      population (TNDH) were mapped to conclude that there are two paralogous copies of
      FAE1, one on each of the B. napus A and C genomes. A new procedure is
      demonstrated to identify novel mutations in situations where two or more very
      similar paralogous gene copies exist in a genome. The procedure involves TILLING
      of single plants, using existing SNPs as a positive control, and is able to
      distinguish novel mutations based on primer pairs designed to amplify both FAE1
      paralogues simultaneously. The procedure was applied to 1344 M2 plants, with 19
      mutations identified, of which three were functionally compromised with reduced
      seed erucic acid content.

PMID- 18811618
TI  - Ecophysiological adjustment of two Sphagnum species in response to anthropogenic
      nitrogen deposition.
AB  - Here, it was investigated whether Sphagnum species have adjusted their nitrogen
      (N) uptake in response to the anthropogenic N deposition that has drastically
      altered N-limited ecosystems, including peatlands, worldwide. A lawn species,
      Sphagnum balticum, and a hummock species, Sphagnum fuscum, were collected from
      three peatlands along a gradient of N deposition (2, 8 and 12 kg N ha(-1) yr(
      1)). The mosses were subjected to solutions containing a mixture of four N forms.
      In each solution one of these N forms was labeled with (15)N (namely
      (15)NH(+)(4), (15)NO(-)(3) and the amino acids [(15)N]alanine (Ala) and
      [(15)N]glutamic acid (Glu)). It was found that for both species most of the N
      taken up was from , followed by Ala, Glu, and very small amounts from NO(-)(3).
      At the highest N deposition site N uptake was reduced, but this did not prevent N
      accumulation as free amino acids in the Sphagnum tissues. The reduced N uptake
      may have been genetically selected for under the relatively short period with
      elevated N exposure from anthropogenic sources, or may have been the result of
      plasticity in the Sphagnum physiological response. The negligible Sphagnum NO(
      )(3) uptake may make any NO(-)(3) deposited readily available to co-occurring
      vascular plants.

PMID- 18811619
TI  - Auxin can act independently of CRC, LUG, SEU, SPT and STY1 in style development
      but not apical-basal patterning of the Arabidopsis gynoecium.
AB  - Patterning of the Arabidopsis thaliana gynoecium is dependent on the localization
      and concentration of the plant hormone auxin and it has been previously reported
      that STYLISH1 (STY1) activates transcription of the auxin biosynthesis gene
      YUCCA4 (YUC4) and affects gynoecium development. Here, the relationship between
      auxin, STY1 and other regulators of gynoecium development was examined. Exogenous
      auxin in droplets of lanolin paste were applied to young gynoecia; auxin
      biosynthesis rate was measured and STY1 overexpression or chemically mediated
      polar auxin transport (PAT) inhibition were induced in various mutants. The style
      phenotype of sty1-1sty2-1 mutants was restored by exogenous application of auxin,
      and STY1 over-activation resulted in an elevated auxin biosynthesis rate. Both
      over-activation of STY1 and inhibition of PAT restored the stylar defects of
      several unrelated mutants, but with regard to gynoecium apical-basal patterning
      the mutants responded differently to inhibition of PAT. These results suggest
      that reduced auxin concentrations cause the sty1-1 sty2-1 phenotype, that STY1
      induces auxin biosynthesis, that elevated apical auxin concentrations can
      compensate for the loss of several style-promoting factors, and that auxin may
      act downstream of, or in parallel with these during style development but is
      dependent on their action in apical-basal patterning.

PMID- 18811620
TI  - Sequestration of soil nitrogen as tannin-protein complexes may improve the
      competitive ability of sheep laurel (Kalmia angustifolia) relative to black
      spruce (Picea mariana).
AB  - The role of litter tannins in controlling soil nitrogen (N) cycling may explain
      the competitive ability of Kalmia relative to black spruce (Picea mariana),
      although this has not been demonstrated experimentally. Here, the protein
      precipitation capacities of purified tannins and leaf extracts from Kalmia and
      black spruce were compared. The resistance to degradation of tannin-protein
      precipitates from both species were compared by monitoring carbon (C) and N
      dynamics in humus amended with protein, purified tannins or protein-tannin
      precipitates. The purity of the precipitates was verified using solid-state (13)C
      nuclear magnetic resonance (NMR) spectra. The ability of mycorrhizal fungi
      associated with both species to grow on media amended with tannin-protein
      complexes as the principal N source was also compared. The protein precipitation
      capacity of Kalmia tannins was superior to those of black spruce. Humus amended
      with protein increased both mineral and microbial N, whereas humus amended with
      tannin-protein precipitates increased dissolved organic N. Mycorrhizal fungi
      associated with Kalmia showed better growth than those associated with black
      spruce when N was provided as tannin-protein precipitates. These data suggest
      that Kalmia litter increases the amount of soil N sequestered as tannin-protein
      complexes, which may improve the competitive ability of Kalmia relative to black
      spruce by favouring N uptake by mycorrhizas associated with the former.

PMID- 18811621
TI  - Identification of conserved core xylem gene sets: conifer cDNA microarray
      development, transcript profiling and computational analyses.
AB  - One approach for investigating the molecular basis of wood formation is to
      integrate microarray profiling data sets and sequence analyses, comparing tree
      species with model plants such as Arabidopsis. Conifers may be included in
      comparative studies thanks to large-scale expressed sequence tag (EST) analyses,
      which enable the development of cDNA microarrays with very significant genome
      coverage. A microarray of 10,400 low-redundancy sequences was designed starting
      from white spruce (Picea glauca (Moench.) Voss) cDNAs. Computational procedures
      that were developed to ensure broad transcriptome coverage and efficient PCR
      amplification were used to select cDNA clones, which were re-sequenced in the
      microarray manufacture process. White spruce transcript profiling experiments
      that compared secondary xylem to phloem and needles identified 360 xylem
      preferential gene sequences. The functional annotations of all differentially
      expressed sequences were highly consistent with the results of similar analyses
      carried out in angiosperm trees and herbaceous plants. Computational analyses
      comparing the spruce microarray sequences and core xylem gene sets from
      Arabidopsis identified 31 transcripts that were highly conserved in angiosperms
      and gymnosperms, in terms of both sequence and xylem expression. Several other
      spruce sequences have not previously been linked to xylem differentiation
      (including genes encoding TUBBY-like domain proteins (TLPs) and a gibberellin
      insensitive (gai) gene sequence) or were shown to encode proteins of unknown
      function encompassing diverse conserved domains of unknown function.

PMID- 18811622
TI  - Association of TNF-alpha with severe respiratory syncytial virus infection and
      bronchial asthma.
AB  - Tumor necrosis factor (TNF-)alpha is a proinflammatory cytokine that is important
      in the innate host defence and thus in the defence of infectious agents. However,
      in excess it provokes the development of chronic inflammatory diseases. The aim
      of this study was to test association of TNF with severe RSV bronchiolitis as
      example of an infectious disease and asthma as representative for a chronic
      inflammatory condition. The following study populations were genotyped for 4
      polymorphisms within TNF-beta (rs909253) and TNF-alpha (rs1799964, rs1799724,
      rs1800629): 322 asthmatic children, 151 children with severe respiratory
      syncytial virus (RSV) bronchiolitis and 270 controls. Furthermore, serum TNF
      alpha levels were measured by a FlowCytomix Assay. Asthma showed association with
      two TNF-alpha polymorphisms as well as with TNF haplotypes (p = 0.0050). In
      contrast, RSV bronchiolitis was associated with TNF haplotypes (p < 0.00001) but
      not with any single polymorphism. In addition, TNF-alpha serum levels correlated
      with rs1799724 (p = 0.034). A genetically mediated up-regulation of TNF-alpha
      expression might provoke a pronounced inflammation of the airways and thus a more
      severe course of RSV infection as well as the onset of asthma. It remains to be
      elucidated whether severe RSV bronchiolitis starts TNF-alpha upregulation and is
      one first step in the direction to asthma later in life, or whether both diseases
      are independent from each other and supported by TNF-alpha upregulation.

PMID- 18811623
TI  - A new PTGDR promoter polymorphism in a population of children with asthma.
AB  - Recently, functional genetic variants of the PTGDR gene have been associated with
      asthma. The objective of this work was to study polymorphisms of the promoter
      region of PTGDR and their haplotype and diplotype combinations in a Spanish
      population of children with asthma. In this study, 200 Caucasian individuals were
      included. Asthma was specialist-physician diagnosed according to the ATS
      criteria. The polymorphisms were analyzed by direct sequencing. In the study, the
      new polymorphism (-613C > T) in the promoter region of PTGDR was analyzed. The CT
      genotype was more common in controls (17%) than in patients with asthma (1%) (p
      value = 0.0003; OR, 0.057; 95% CI, 0.007-0.441). The CCCT CCCC diplotype
      (promoter positions -613, -549, -441, and -197) was more frequent in the group of
      patients with asthma [Fisher's p-value = 0.012; OR, 10.24; 95% CI (1.25-83.68)];
      this diplotype is unambiguous. To our knowledge, this is the first study of -613C
      > T PTGDR polymorphism in patients. This analysis provides more complete
      information on influence of diplotype combinations of PTGDR polymorphisms in
      asthma.

PMID- 18811624
TI  - Quantification of the effect of nonphotochemical quenching on the determination
      of in vivo chl a from phytoplankton along the water column of a freshwater
      reservoir.
AB  - Nonphotochemical quenching (NPQ) is a well-known collection of different
      photoprotective mechanisms of plants and algae to avoid photodamage under an
      excess of light energy. In order to evaluate the overall effect of NPQ processes
      on the fluorometric determination of in vivo Chl a from a phytoplankton community
      dominated by diatoms, we compared the results obtained by two different
      fluorometric field devices with the total concentration of extracted Chl a
      measured by HPLC (in vitro Chl a). A different set of measurements were made to
      assess the performance of these fluorometers at high, moderate and low irradiance
      conditions. The Fbbe fluorometer, which is capable of distinguishing different
      algal groups according to their pigment content, allowed a better determination
      of in vivo Chl a under high irradiance conditions, with only a 10% mean
      difference from the in vitro Chl a concentration. In turn, the FMII fluorometer
      underestimated by as much as 50% the in vitro Chl a concentration under the same
      light conditions. As data from both fluorometers were in accordance with the in
      vitro Chl a values at moderate irradiance levels, the differences observed at
      high irradiances were attributed to the decrease in the yield of Chl a
      fluorescence caused by photoprotective NPQ processes. Accordingly, we estimated
      the effect of NPQ processes on the in vivo Chl a determination and the results
      allow us to provide an equation to correct this effect when in situ fluorometric
      measurements are carried out under high irradiance regimes. Our results
      demonstrate that under certain circumstances NPQ seriously compromises the
      results obtained by in situ fluorometric probes and highlight the need for a
      cautious interpretation of field data under such environmental conditions.

PMID- 18811625
TI  - Laboratory and outdoor assessment of UV protection offered by flax and hemp
      fabrics dyed with natural dyes.
AB  - The safest protection from UV radiation (UVR) exposure is offered by clothing and
      its protectiveness depends on fabric composition (natural, artificial or
      synthetic fibers), fabric parameters (porosity, weight and thickness) and dyeing
      (natural or synthetic dyes, dye concentration, UV absorbing properties, etc.). In
      this study the UV protection properties of two fabrics made of natural fibers
      (flax and hemp) dyed with some of the most common natural dyes were investigated.
      UVR transmittance of fabrics was measured by two methods: one based on the
      utilization of a spectrophotometer equipped with an integrating sphere (in vitro
      test), and the other based on outdoor measurements taken by a spectroradiometer.
      Transmittance measurements were used to calculate the ultraviolet protection
      factor (UPF). Experimental results revealed that natural dyes could confer good
      UV protection, depending mainly on their different UVR-absorbing properties,
      provided that the fabric construction already guaranteed good cover. An increase
      in cover factor caused by the dyeing process was also detected. Weld-dyed fabrics
      gave the highest protection level. The comparison between the two methods applied
      to measure fabric transmittance pointed out that the UPFs calculated by in vitro
      measurements were generally lower than those based on outdoor data, indicating an
      underestimation of the actual protection level of tested fabrics assessed by the
      in vitro test.

PMID- 18811626
TI  - The speeding of voluntary reaction by a warning signal.
AB  - Warning signals can shorten reaction time (RT) via either a top-down mechanism,
      temporal attention, or a bottom-up one, phasic arousal. The goal of this review
      article is to identify the locus at which these processes influence RT.
      Electrophysiological and behavioral evidence indicate that the chronometric locus
      for both modulatory effects lies mainly within a narrow window at the center of
      the stimulus-response interval. This interval presumably encompasses late
      perceptual, response selection, and early motor processes. Phasic arousal is
      theorized to reduce the threshold for response selection within a circuit
      involving the supramarginal gyrus. A blind-sight study indicates that conscious,
      cortical level processing is necessary for temporal attention, at least when the
      warning signal is visual.

PMID- 18811627
TI  - Recovery and cryopreservation of epididymal sperm of plains bison (Bison bison
      bison) as a model for salvaging the genetics of wood bison (Bison bison
      athabascae).
AB  - The objective of this study was to optimize recovery and cryopreservation of
      epididymal sperm from plains bison, as a model for wood bison. In Phase 1, cauda
      epididymides were recovered from bison (n = 14) immediately after slaughter,
      minced and incubated in Sp-TALPH buffer for 3 h at 36 degrees C. The resulting
      sperm suspensions were cryopreserved in Triladyl, using a protocol for bovine
      semen. In Phase 2, epididymal sperm were cryopreserved in either Triladyl or
      Andromed. The mean (+/-SD) estimated number of sperm recovered was 468 +/- 207 x
      10(6). There was an increase (p < 0.05) in the proportion of sperm with normal
      morphology between initial recovery and after extension (52.4 +/- 4.6 vs 69.7 +/-
      2.4%), with a concurrent decrease (p < 0.05) in the proportion of sperm with
      distal droplets. Median values for progressively motile sperm in post-thaw
      samples (60%) were lower (p < 0.05) than that after extension or after chilling
      (70% for both). The mean percentages of viable sperm and of sperm with an intact
      acrosome were lower (p < 0.05) for frozen-thawed samples (38.7 +/- 2.8 and 85.2
      +/- 1.1) compared with extended (66.2 +/- 2.2 and 92.4 +/- 0.9) or chilled (63.7
      +/- 2.5 and 90.0 +/- 1.0) samples. Rates of cleavage, morulae and blastocyst
      production were not significantly different for chilled (70.9, 38.7 and 8.0%) vs
      post-thaw sperm (73.0, 46.0 and 6.3%). There was no significant difference
      between extenders for most sperm characteristics. In conclusion, we developed a
      functional protocol for the recovery and cryopreservation of epididymal sperm
      from plains bison, which may have implications for the genetic preservation of
      wood bison.

PMID- 18811628
TI  - New immunosuppressive strategies and the risk of infection.
AB  - Newer immunosuppressive strategies have resulted in a marked reduction in graft
      rejection after transplantation, with the price being an increase of infectious
      complications, such as BK-related nephropathy. The targeting of new
      immunosuppressive pathways, such as interleukin-2-mammalian target of rapamycin
      inhibition, may have unexpected consequences for the immune response. Cell
      depleting agents have long-lasting effects on cellular recovery and function,
      with the activation of latent viral infections and late viral and fungal
      infections. The multitude of different induction and maintenance protocols
      renders the detection of small increases of often rare infections very difficult.
      At the same time, preemptive and prophylactic strategies have gained widespread
      acceptance and may further offset small changes in infection rates. Other factors
      related to an increase or shift of infections may be of equal importance, such as
      increased use of marginal donors, older age at transplantation, or more patients
      receiving a second transplant. Not all the changes observed result in an
      increased immunosuppression. Steroid- and calcineurin inhibitor-sparing protocols
      may have a beneficial impact on infectious complications. Antimycotic or
      antiviral activity has been described for specific immunosuppressive agents,
      although the in vivo effect of these activities is uncertain. The possible role
      of specific drugs in the occurrence of infections is discussed, with emphasis on
      the antibodies and fusion proteins. The unequivocal attribution of a given
      infection to a specific drug is often impossible, as the risk of infection is
      dependent on the entirety of immunosuppression and the epidemiological pressure
      ('net immunosuppression'). It is important to remain vigilant for unexpected
      infections, not only in the context of clinical studies with selected patients,
      but also in the routine follow-up of our transplant patients.

PMID- 18811629
TI  - Deficiency of cytomegalovirus (CMV)-specific CD8+ T cells in patients presenting
      with late-onset CMV disease several years after transplantation.
AB  - Cytomegalovirus (CMV) is a major cause of morbidity and mortality among
      transplant recipients. The routine use of anti-CMV prophylaxis has modified the
      epidemiology of post-transplant CMV infection by delaying the onset of clinical
      disease. While the majority of delayed-onset CMV disease still occurs during the
      first year after transplant, reports of late-onset CMV disease presenting many
      years after transplantation are increasing. Here, we describe 2 CMV-seropositive
      transplant recipients who presented with late-onset CMV disease at 8 and 11 years
      after transplantation. To determine whether CMV disease occurring at a very late
      period after transplantation is related to immune competence, we assessed global
      and CMV-specific cellular immunity by evaluating the activation capability of
      CD8+ T cells to a mitogenic stimulus and by quantitative and functional analysis
      (as assessed by intracellular cytokine production and degranulation) of CMV
      specific CD8+ T cells. In both patients, we demonstrated the absence or marked
      deficiency of CMV-specific T-cell immunity despite CMV seropositivity, and in one
      patient, a partial defect in the immune response to phorbol myristate acetate and
      ionomycin suggesting impaired global immune competence. Hence, our data suggest
      that late-onset CMV disease occurring many years after transplantation remains
      related to defects in the immune competence of patients. Measurement of CMV
      specific cellular immune competence may therefore provide an additional tool to
      screen for patients at high risk of developing late-onset CMV disease. The
      clinical utility of this assay, however, will need to be evaluated in larger
      prospective studies.

PMID- 18811630
TI  - Community-acquired methicillin-resistant Staphylococcus aureus endomyocardial
      abscesses in a heart transplant recipient.
AB  - Infective endocarditis is more common in heart transplant recipients than in the
      general population. We report a case of endomyocardial abscesses and sepsis
      syndrome due to community-acquired methicillin-resistant Staphylococcus aureus
      (MRSA) in a heart transplant recipient with a negative transesophageal
      echocardiogram. The suspected portal of entry for this MRSA infection was through
      infected herpes zoster lesions. This case demonstrates the difficulty of
      diagnosing endomyocardial abscesses in heart transplant patients.

PMID- 18811631
TI  - Prospective monitoring of BK virus replication in renal transplant recipients.
AB  - BACKGROUND: BK virus-associated nephropathy (BKVAN) can be diagnosed only with
      renal graft biopsy. Definitive diagnosis of BKVAN requires demonstration of BK
      virus (BKV) replication in renal allograft tissues. Non-invasive analysis of
      urine and blood is considered essential in screening renal transplant recipients.
      PATIENTS AND METHODS: This study evaluated prospectively the replication of BKV
      in plasma and urine with qualitative and quantitative real-time polymerase chain
      reaction in 32 de novo (group A) and 34 chronic (group B) renal transplant
      recipients and the long-term impact on graft function. RESULTS: In group A, 456
      samples (228 plasma, 228 urine) were examined and BKV was detected in 31 (31/228,
      14%) samples of plasma and 57 (57/228, 25%) samples of urine in 20 (20/32, 62.5%)
      and 23 (23/32, 72%) recipients, respectively. Incidence of viremia and viruria
      increased during the first 6 months presenting a peak the third postoperative
      month (viremia: 28% and viruria: 31%). Immune suppressive treatment with
      tacrolimus showed significant relation with viremia. Renal graft function in de
      novo renal transplant recipients remained stable throughout the follow-up period
      without influence of BKV replication. In group B, incidence of viremia and
      viruria were 3% (1/34) and 9% (3/34) correspondingly, indicating that after the
      first post-transplant year the risk of BKV re-activation is diminished.
      CONCLUSION: The highest incidence of BK viremia and viruria is observed the third
      post-transplantation month, confirming previously published studies in Europe and
      the United States, and long-term follow up shows that BKV replication decreases
      significantly after the third post-transplant month and even transient viremia or
      viruria does not have an impact on renal function.

PMID- 18811632
TI  - Pseudomonas aeruginosa infection after living-donor liver transplantation in
      adults.
AB  - OBJECTIVES: Pseudomonas aeruginosa infection is a major cause of bacterial
      infection after deceased-donor liver transplantation. The incidence and risk
      factors of P. aeruginosa infection after living-donor liver transplantation
      (LDLT), however, are not known. METHODS: We retrospectively reviewed the data
      from 170 adult patients who underwent LDLT at the University of Tokyo Hospital.
      The microbiologic and medical records of the patients from admission to 3 months
      after LDLT were reviewed. Uni- and multivariate analyses were performed to
      identify the independent risk factors for postoperative P. aeruginosa infection.
      RESULT: Preoperative P. aeruginosa carriage was identified in 15 (9%) patients.
      Only 2 of the 15 patients later presented with postoperative P. aeruginosa
      infection. Postoperative P. aeruginosa infection occurred in 27 (16%) of 170
      patients by median postoperative day 38. Among those 27 patients, surgical site
      infections were recorded in 8 (30%) and intra-abdominal infections in 14 (52%).
      In 5 of the 27 (19%) patients, P. aeruginosa isolates were multiple antimicrobial
      resistant. Postoperative bile leakage independently predicted postoperative P.
      aeruginosa infection. CONCLUSION: P. aeruginosa infections were frequently
      detected after LDLT, including those by multiple antimicrobial-resistant
      isolates. Postoperative bile leakage predisposed patients to P. aeruginosa
      infection. Surveillance culture should be checked periodically after LDLT to
      ensure that appropriate antimicrobials can be administered for postoperative
      infection.

PMID- 18811633
TI  - Vibrio cholerae non-O1 infection in cirrhotics: case report and literature
      review.
AB  - Vibrio species are ubiquitous in the marine environment and can cause severe
      infections in cirrhotic patients. Patients with liver disease should be warned
      about the potential dangers of consuming raw or undercooked seafood, and avoiding
      exposure of wounds to seawater. We report a case of severe sepsis from Vibrio
      cholerae non-O1 in a patient with cirrhosis awaiting orthotopic liver transplant.
      This case is aimed to advise clinicians about the importance of V. cholerae
      subtypes, and non-cholera Vibrio species infections in cirrhotic patients,
      highlighting the need to educate these patients to stay away from undercooked
      seafood.

PMID- 18811634
TI  - Listeria grayi bacteremia in a heart transplant recipient.
AB  - Bacteria belonging to the genus Listeria have been isolated from food products of
      animal, plant, and fish origin, and are associated with infections in
      immunocompromised hosts, pregnant women, and infants. The species Listeria grayi
      has rarely been reported as a human pathogen. It has a unique antibiotic
      sensitivity profile. We describe a case of L. grayi bacteremia in a heart
      transplant recipient. The organism demonstrated a reduced sensitivity to
      ampicillin. The patient was successfully treated with a combination of vancomycin
      and ciprofloxacin.

PMID- 18811635
TI  - Research opportunities in simulation-based medical education using deliberate
      practice.
AB  - There are many opportunities for the academic emergency medicine (EM) community
      to engage in simulation-based educational research using deliberate practice
      (DP). This article begins by defining and giving examples of two key concepts:
      deliberate practice and mastery learning. The article proceeds to report six
      lessons learned from a research legacy in simulation-based medical education
      (SBME). It concludes by listing and amplifying 10 DP research opportunities in
      academic EM. A coda states that the research agenda is rich and ambitious and
      should focus on the goal of educating superb, expert clinicians.

PMID- 18811636
TI  - The consent and prescription compliance (COPRECO) study: does obtaining consent
      in the emergency department affect study results in a telephone follow-up study
      of medication compliance?
AB  - OBJECTIVES: The objectives were to determine whether mandated research
      requirements for consent in the emergency department (ED) falsely distorts the
      results of a survey of patient-reported compliance with ED prescriptions and, in
      addition, to ascertain the level of patient compliance to medication instructions
      and find out the degree of displeasure expressed by patients called without prior
      consent. METHODS: Patients given new prescriptions for a medicine to be taken
      regularly over a period of less than 30 days were eligible. A convenience sample
      of eligible patients was randomized to having consent obtained during their ED
      visit or at the time of telephone follow-up. Patients were called 7-10 days after
      their ED visit to determine their compliance with the prescription. Compliance
      rates between the two groups were compared, as was the prevalence of displeasure
      expressed by patients called without prior consent. RESULTS: Of 430 enrolled
      patients, 221 were randomized to receive ED consent for telephone follow-up, and
      209 received telephone follow-up without prior ED consent. Telephone follow-up
      was successful in 318 patients (74%). The rate of noncompliance was slightly
      higher in the group without ED consent, 74/149 (50%; 95% confidence interval [CI]
      = 41% to 58%) than the group who gave ED consent for telephone follow-up, 67/169
      (40%; 95% CI = 32% to 42%; p = 0.07). Among the two groups, 141/318 (44%) did not
      fill the prescription (n = 42) or took it incorrectly (n = 99). Only 1 (0.7%) of
      the 149 patients with successful telephone follow-up without prior ED consent
      expressed displeasure at this telephone call. CONCLUSIONS: Medicine noncompliance
      is a significant issue for patients discharged from the ED in this study.
      Although there was a trend toward greater compliance in patients who consented to
      the follow-up call, this did not reach statistical significance. ED patients do
      not object to receiving telephone follow-up for a research survey without giving
      prior consent.

PMID- 18811637
TI  - Visual fields and optic disc morphology in very low birthweight adolescents
      examined with magnetic resonance imaging of the brain.
AB  - PURPOSE: We aimed to evaluate visual fields (VFs) and optic disc morphology in
      very low birthweight (VLBW) adolescents compared with age- and gender-matched
      controls, and to relate the findings to magnetic resonance imaging (MRI) results.
      METHODS: Fifty-nine VLBW adolescents and 55 age- and gender-matched controls with
      normal birthweight were examined. Visual fields were tested using computerized
      rarebit perimetry (RB). Optic nerve and retinal vessel morphology were evaluated
      by digital image analysis of fundus photographs. Brain MRI was conducted in the
      VLBW subjects. RESULTS: Ten of the 57 VLBW subjects (p = 0.022) had subnormal VF
      results defined as a mean hit rate below the fifth percentile of the controls
      (i.e. < 89%). All of these also had significantly lower mean hit rates (p =
      0.039) in the inferior hemifield. Sixteen of 57 (28%) VLBW subjects had white
      matter damage of immaturity (WMDI) on MRI. Six of 15 subjects with WMDI (who
      underwent VF testing) also had subnormal RB results, compared with four of 39
      with normal MRI findings (p = 0.02). The mean neural retinal rim area was 9%
      smaller (p = 0.018) in the VLBW group than in the control group. The VLBW
      adolescents had a significantly higher index for tortuosity of arterioles than
      the controls (p < 0.001). CONCLUSIONS: In the present study, 18% of all VLBW
      adolescents and 40% of those with WMDI had subnormal RB VF findings. The VLBW
      group had increased arterial tortuosity and a somewhat smaller (9%) mean neural
      retinal rim area than the control group. Thus sequels to VLBW appear to persist
      in adolescence.

PMID- 18811638
TI  - Longitudinal study of anterior segment inflammation by ultrasound biomicroscopy
      in patients with acute anterior uveitis.
AB  - PURPOSE: This study aimed to investigate dynamic changes in the anterior segment
      in patients with acute anterior uveitis (AAU) using ultrasound biomicroscopy
      (UBM). METHODS: Acute anterior uveitis was diagnosed in 18 patients according to
      history and ocular examinations. Ultrasound biomicroscopy was performed and the
      results at three time-points (within 2 weeks of the uveitis attack, and at 2-4
      weeks and 6 weeks after it) were analysed. The relationships between clinical
      manifestations and UBM findings were also evaluated. RESULTS: All investigated
      AAU patients showed severe ciliary injection, numerous dust keratic precipitates
      (KPs), aqueous flare and inflammatory cells, and were treated predominantly with
      corticosteroid and cycloplegic eyedrops. Ultrasound biomicroscopy showed a large
      number of cells in the anterior and posterior chamber, marked oedema and exudates
      in and around the iris and ciliary body within 2 weeks of AAU onset. These
      abnormalities were dramatically improved at 2-4 weeks and almost resolved at 6
      weeks and thereafter. CONCLUSIONS: Ultrasound biomicroscopy reveals severe
      inflammatory changes in and around the ciliary body in patients with AAU. These
      signs rapidly resolve upon treatment.

PMID- 18811639
TI  - A population-based study of macular thickness in full-term children assessed with
      Stratus OCT: normative data and repeatability.
AB  - PURPOSE:  We aimed to determine normal macular thickness values, assessed with
      optical coherence tomography (OCT), in a population of full-term children of
      normal birthweight. METHODS:  A total of 56 children, aged 5-16 years, randomly
      chosen from the population register, were examined with Stratus OCT. Only
      children with visual acuity < 0.2 logMAR, spherical equivalent of - 3 to + 3 D
      and astigmatism < 2 D were included. The fast macular map protocol was used and
      three examinations were performed in each eye. One eye was then randomized for
      further analyses. Mean values for the nine ETDRS areas, foveal minimum thickness
      and macular volume were calculated for 55 eyes. Coefficients of variance and
      intraclass correlations were calculated for each area. RESULTS: All children co
      operated well and no child was excluded for lack of concentration. Mean +/-
      standard deviation central macular thickness was 204 +/- 19 MUm. Mean total
      macular volume was 7.11 +/- 0.35 mm(3). No correlations were found between age,
      gender and macular thickness. Coefficients of variance were < 2% and intraclass
      correlations were > 0.9 in all areas, except the foveal minimum. CONCLUSIONS:
      Normal values for macular thickness in healthy full-term children were reported.
      As the Stratus OCT provides normal values only for adults, these data are a
      better alternative for comparison with children with retinal abnormalities. We
      concluded that OCT is suitable for examining the retina in children aged 5-16
      years and has the same high level of repeatability as in adults.

PMID- 18811640
TI  - Scanning laser polarimetry with variable corneal compensation in migraine
      patients.
AB  - PURPOSE:  This study aimed to compare scanning laser polarimetry measurements of
      retinal nerve fibre layer (RNFL) thickness in eyes of migraine patients with
      those in eyes of age-matched, healthy subjects. METHODS:  The study was designed
      as an observational, prospective, cross-sectional study. It included 57 eyes of
      57 patients with migraine with or without aura according to the criteria of the
      International Headache Society and 44 eyes of 44 age-matched healthy controls.
      Scanning laser polarimetry images were obtained using a commercial GDx VCC system
      (Version 5.3.1; Laser Diagnostic Technologies, Inc.). At each sitting, three sets
      of GDx VCC measurements were acquired for each patient and used in the analysis.
      Image acquisition was performed in undilated eyes in all subjects. RESULTS:  The
      mean +/- standard deviation RNFL average thickness parameter in the migraine
      subjects was significantly lower than in the control group, at 50.4 +/- 4.8 MUm
      versus 54.7 +/- 3.4 MUm, respectively (p < 0.0001). However, there were no
      differences between migraine subjects and controls in mean RNFL thickness in
      superior and inferior areas. In the migraine group the mean migraine disability
      assessment (MIDAS) score was 34.3 +/- 15.3 and the mean number of attacks per
      year was 17.1 +/- 6.9 (range 6-28). The mean RNFL average thickness parameter was
      significantly correlated with MIDAS score (r = - 0.86, p < 0.0001) and frequency
      of attacks (r = - 0.86, p < 0.0001). CONCLUSIONS: The mean RNFL average thickness
      parameter was found to be thinner in migraine patients. In addition, we found a
      strong correlation between migraine severity and RNFL average thickness
      parameters.

PMID- 18811641
TI  - Bevacizumab as adjuvant for neovascular glaucoma.
AB  - PURPOSE: We aimed to evaluate the longterm effects of intraocular bevacizumab
      (Avastin) injections as adjuvant treatment in patients with neovascular glaucoma.
      METHODS: Twenty eyes of 18 consecutive patients with secondary neovascular
      glaucoma caused by proliferative diabetic retinopathy (n = 7), ischaemic central
      retinal vein occlusion (n = 7), ischaemic ophthalmopathy (n = 2) and retinal
      ischaemia resulting from persistent detachment (n = 2) were treated with
      intraocular bevacizumab injections (1.25 mg/0.05 ml) in addition to other
      treatments. The main outcome measure was the change in degree of iris rubeosis.
      Secondary outcomes included intraocular pressure (IOP), best corrected visual
      acuity (BCVA) and numbers of additional interventions or antiglaucoma medications
      administered after injection. RESULTS: Mean (+/- standard deviation) follow-up
      was 67.7 +/- 13.8 weeks (range 50-93 weeks). At the last follow-up, complete
      regression of rubeosis was detectable in five (20%) eyes, incomplete regression
      in seven (35%), stabilization in six (30%), and an increase in two (10%) eyes.
      Mean IOP was 26.0 +/- 8.9 mmHg at baseline and significantly decreased to 14.75
      +/- 5.3 mmHg at the last follow-up visit (p = 0.000005). Mean baseline BCVA
      (logMAR [logarithm of the minimum angle of resolution] 1.43 +/- 0.89) was
      stabilized during the follow-up period (logMAR 1.5 +/- 0.98). Patients received
      an average of 2.75 injections. Additional treatments were laser photocoagulation
      in 13 (65%) eyes, cyclodestructive procedure in 14 (70%), cryopexy in six (30%),
      drainage procedures in two (10%), and vitrectomy in five (25%) eyes. CONCLUSIONS:
      Bevacizumab may be beneficial as adjuvant treatment in neovascular glaucoma
      because of its anti-angiogenic properties and its ability to prevent
      establishment or progression of angular obstruction. The causative disease
      inducing the angiogenic process requires treatment in all cases. Antiglaucoma
      treatment is needed in cases of persistent elevated IOP.

PMID- 18811642
TI  - Development of new lymphatic vessels in alkali-burned corneas.
AB  - PURPOSE: Corneal lymphangiogenesis provides an exit route for antigen-presenting
      cells to regional lymph nodes, inducing immune response. The purpose of this
      study was to examine the development of corneal lymphatic vessels in alkali
      burned corneas. METHODS: Corneal lymphatic vessels were examined by electron
      microscopy, 5'-nase-alkaline phosphatase (5'-NA-ALP) double enzyme-histochemistry
      and whole mount immunofluorescence at 6 hr, 1 day, 3 days, and 1, 2, 3, 4, 5, 6,
      7 and 8 weeks after rat corneal alkali injury. The expression of vascular
      endothelial growth factor-C (VEGF-C) protein and mRNA was examined 1, 3, 5, 7, 9,
      11 and 14 days after the injury. RESULTS: Corneal lymphangiogenesis developed 3
      days after alkaline burns, reached its peak 2 weeks after the injury, decreased
      gradually and disappeared at the end of the fifth week. The expression of VEGF-C
      in burned corneas increased dramatically on the third day but disappeared the
      14th day after the injury. CONCLUSION: Corneal lymphatic vessels develop after
      alkaline burns and VEGF-C may play an important role in corneal lymphangiogensis.

PMID- 18811643
TI  - Anaerobic degradation of naphthalene and 2-methylnaphthalene by strains of marine
      sulfate-reducing bacteria.
AB  - The anaerobic biodegradation of naphthalene, an aromatic hydrocarbon in tar and
      petroleum, has been repeatedly observed in environments but scarcely in pure
      cultures. To further explore the relationships and physiology of anaerobic
      naphthalene-degrading microorganisms, sulfate-reducing bacteria (SRB) were
      enriched from a Mediterranean sediment with added naphthalene. Two strains
      (NaphS3, NaphS6) with oval cells were isolated which showed naphthalene-dependent
      sulfate reduction. According to 16S rRNA gene sequences, both strains were
      Deltaproteobacteria and closely related to each other and to a previously
      described naphthalene-degrading sulfate-reducing strain (NaphS2) from a North Sea
      habitat. Other close relatives were SRB able to degrade alkylbenzenes, and
      phylotypes enriched anaerobically with benzene. If in adaptation experiments the
      three naphthalene-grown strains were exposed to 2-methylnaphthalene, this
      compound was utilized after a pronounced lag phase, indicating that naphthalene
      did not induce the capacity for 2-methylnaphthalene degradation. Comparative
      denaturing gel electrophoresis of cells grown with naphthalene or 2
      methylnaphthalene revealed a striking protein band which was only present upon
      growth with the latter substrate. Peptide sequences from this band perfectly
      matched those of a protein predicted from genomic libraries of the strains.
      Sequence similarity (50% identity) of the predicted protein to the large subunit
      of the toluene-activating enzyme (benzylsuccinate synthase) from other anaerobic
      bacteria indicated that the detected protein is part of an analogous 2
      methylnaphthalene-activating enzyme. The absence of this protein in naphthalene
      grown cells together with the adaptation experiments as well as isotopic
      metabolite differentiation upon growth with a mixture of d(8)-naphthalene and
      unlabelled 2-methylnaphthalene suggest that the marine strains do not metabolize
      naphthalene by initial methylation via 2-methylnaphthalene, a previously
      suggested mechanism. The inability to utilize 1-naphthol or 2-naphthol also
      excludes these compounds as free intermediates. Results leave open the
      possibility of naphthalene carboxylation, another previously suggested activation
      mechanism.

PMID- 18811644
TI  - Dynamic secondary ion mass spectrometry imaging of microbial populations
      utilizing C-labelled substrates in pure culture and in soil.
AB  - We demonstrate that dynamic secondary ion mass spectrometry (SIMS)-based ion
      microscopy can provide a means of measuring (13)C assimilation into individual
      bacterial cells grown on (13)C-labelled organic compounds in the laboratory and
      in field soil. We grew pure cultures of Pseudomonas putida NCIB 9816-4 in minimal
      media with known mixtures of (12)C- and (13)C-glucose and analysed individual
      cells via SIMS imaging. Individual cells yielded signals of masses 12, 13, 24,
      25, 26 and 27 as negative secondary ions indicating the presence of (12)C(-),
      (13)C(-), (24)((12)C(2))(-), (25)((12)C(13)C)(-), (26)((12)C(14)N)(-) and
      (27)((13)C(14)N)(-) ions respectively. We verified that ratios of signals taken
      from the same cells only changed minimally during a approximately 4.5 min period
      of primary O(2)(+) beam sputtering by the dynamic SIMS instrument in microscope
      detection mode. There was a clear relationship between mass 27 and mass 26
      signals in Pseudomonas putida cells grown in media containing varying proportions
      of (12)C- to (13)C-glucose: a standard curve was generated to predict (13)C
      enrichment in unknown samples. We then used two strains of Pseudomonas putida
      able to grow on either all or only a part of a mixture of (13)C-labelled and
      unlabelled carbon sources to verify that differential (13)C signals measured by
      SIMS were due to (13)C assimilation into cell biomass. Finally, we made three key
      observations after applying SIMS ion microscopy to soil samples from a field
      experiment receiving (12)C- or (13)C-phenol: (i) cells enriched in (13)C were
      heterogeneously distributed among soil populations; (ii) (13)C-labelled cells
      were detected in soil that was dosed a single time with (13)C-phenol; and (iii)
      in soil that received 12 doses of (13)C-phenol, 27% of the cells in the total
      community were more than 90% (13)C-labelled.

PMID- 18811645
TI  - Role of menaquinone biosynthesis genes in selenate reduction by Enterobacter
      cloacae SLD1a-1 and Escherichia coli K12.
AB  - In this study, we investigated the role of menaquinone biosynthesis genes in
      selenate reduction by Enterobacter cloacae SLD1a-1 and Escherichia coli K12. A
      mini-Tn5 transposon mutant of E. cloacae SLD1a-1, designated as 4E6, was isolated
      that had lost the ability to reduce Se(VI) to Se(0). Genetic analysis of mutant
      strain 4E6 showed that the transposon was inserted within a menD gene among a
      menFDHBCE gene cluster that encodes for proteins required for menaquinone
      biosynthesis. A group of E. coli K12 strains with single mutations in the menF,
      menD, menC and menE genes were tested for loss of selenate reduction activity.
      The results showed that E. coli K12 carrying a deletion of either the menD, menC
      or menE gene was unable to reduce selenate. Complementation using wild-type
      sequences of the E. cloacae SLD1a-1 menFDHBCE sequence successfully restored the
      selenate reduction activity in mutant strain 4E6, and E. coli K12 menD and menE
      mutants. Selenate reduction activity in 4E6 was also restored by chemical
      complementation using the menaquinone precursor compound 1,4-dihydroxy-2
      nathphoic acid. The results of this work suggest that menaquinones are an
      important source of electrons for the selenate reductase, and are required for
      selenate reduction activity in E. cloacae SLD1a-1 and E. coli K12.

PMID- 18811647
TI  - Assessment of metabolic diversity within the intestinal microbiota from healthy
      humans using combined molecular and cultural approaches.
AB  - The human gut harbours a wide range of bacterial communities that play key roles
      in supplying nutrients and energy to the host through anaerobic fermentation of
      dietary components and host secretions. This fermentative process involves
      different functional groups of microorganisms linked in a trophic chain. Although
      the diversity of the intestinal microbiota has been studied extensively using
      molecular techniques, the functional aspects of this biodiversity remain mostly
      unexplored. The aim of the present work was to enumerate the principal metabolic
      groups of microorganisms involved in the fermentative process in the gut of
      healthy humans. These functional groups of microorganisms were quantified by a
      cultural approach, while the taxonomic composition of the microbiota was assessed
      by in situ hybridization on the same faecal samples. The functional groups of
      microorganisms that predominated in the gut were the polysaccharide-degrading
      populations involved in the breakdown of the most readily available exogenous and
      endogenous substrates and the predominant butyrate-producing species. Most of the
      functional groups of microorganisms studied appeared to be present at rather
      similar levels in all healthy volunteers, suggesting that optimal numbers of
      these various bacterial groups are crucial for efficient gut fermentation, as
      well as for host nutrition and health. Significant interindividual differences
      were, however, confirmed with respect to the numbers of methanogenic archaea,
      filter paper-degrading and acetogenic bacteria and the products formed by lactate
      utilizing bacteria.

PMID- 18811648
TI  - Growth, encystment and survival of Acanthamoeba castellanii grazing on different
      bacteria.
AB  - Free-living amoebae of the genus Acanthamoeba are widely distributed in soil and
      water collections, where trophozoites (vegetative, multiplicative stages) feed
      mainly by phagocytosis and thus control bacterial populations in the environment.
      Here, we examined the growth, encystment and survival of Acanthamoeba castellanii
      receiving different bacteria (Escherichia coli, Pseudomonas aeruginosa,
      Enterobacter cloacae, Bacillus subtilis, Bacillus megaterium, Micrococcus luteus,
      and Staphylococcus aureus) in nonnutrient saline. All bacteria assayed induced a
      dose-dependent proliferative response, in most cases maximized with a bacterial
      dose of 1 x 10(9) mL(-1); except for M. luteus, trophozoites grew better with
      viable than with heat-killed bacteria. In addition, Acanthamoeba growth was
      improved by adding bacteria on alternate days. Single-dose experiments indicated
      a temporal association between the growth of trophozoite and bacterial
      consumption, and higher consumption of M. luteus, E. coli and P. aeruginosa,
      bacterial species that allowed the highest trophozoite yields. Long-term
      Acanthamoeba-bacteria incubation revealed that encystment was significantly
      delayed by almost all the bacteria assayed (including S. aureus, which elicited a
      poor growth response) and that the presence of bacteria markedly increased cyst
      yield; final cyst recovery clearly depended on both the dose and the type of the
      bacterium given, being much higher with E. coli, M. luteus and P. aeruginosa.

PMID- 18811649
TI  - Nutrient effects on the genetic and functional diversity of aquatic bacterial
      communities.
AB  - Studies on the effects of biodiversity on ecosystem functioning have generally
      revealed a positive asymptotic relationship between biodiversity and single
      functions, suggesting species redundancy with respect to these functions.
      However, most research was performed on specific processes and did not consider
      ecosystem 'multifunctionality'. There is also little information on the
      relationship between genetic and functional diversity. To analyze this
      relationship, we performed a microcosm experiment on a complex lake assemblage of
      decomposers, in the presence of the green alga Scenedesmus obliquus, which acted
      as carbon source for decomposers. By manipulating nutrient enrichment and the N :
      P input ratio, we observed that the structures of particle-associated and free
      bacterial assemblages were highly predictable in response to stoichiometric
      constraints. For a given treatment, the taxonomic compositions of free and
      particle-associated bacterial communities appeared close to each other only when
      phosphorus was not depleted. A coinertia analysis revealed a clear coupling
      between the genetic diversity of the microbial community, assessed using PCR
      denatured gradient gel electrophoresis, and its potential functional diversity,
      studied with Biolog Ecoplates. This suggests that an ecologically relevant
      fraction of bacterial communities is characterized by lower level of redundancy
      than frequently thought, highlighting the necessity of exploring further the role
      of biodiversity in multifunctionality within ecosystems.

PMID- 18811650
TI  - Physiology of phototrophic iron(II)-oxidizing bacteria: implications for modern
      and ancient environments.
AB  - Phototrophic iron(II) [Fe(II)]-oxidizing bacteria are present in modern
      environments and evidence suggests that this metabolism was present already on
      early earth. We determined Fe(II) oxidation rates depending on pH, temperature,
      light intensity, and Fe(II) concentration for three phylogenetically different
      phototrophic Fe(II)-oxidizing strains (purple nonsulfur bacterium Rhodobacter
      ferrooxidans sp. strain SW2, purple sulfur bacterium Thiodictyon sp. strain F4,
      and green sulfur bacterium Chlorobium ferrooxidans strain KoFox). While we found
      the overall highest Fe(II) oxidation rates with strain F4 (4.5 mmol L(-1) day(
      1), 800 lux, 20 degrees C), the lowest light saturation values [at which maximum
      Fe(II) oxidation occurred] were determined for strain KoFox with light saturation
      already below 50 lux. The oxidation rate per cell was determined for R.
      ferrooxidans strain SW2 to be 32 pmol Fe(II) h(-1) per cell. No significant toxic
      effect of Fe(II) was observed at Fe(II) concentrations of up to 30 mM. All three
      strains are mesophiles with upper temperature limits of c. 30 degrees C. The main
      pigments were identified to be spheroidene, spheroidenone, OH-spheroidenone
      (SW2), rhodopinal (F4), and chlorobactene (KoFox). This study will improve our
      ecophysiological understanding of iron cycling in modern environments and will
      help to evaluate whether phototrophic iron oxidizers may have contributed to the
      formation of Fe(III) on early earth.

PMID- 18811651
TI  - Methane assimilation and trophic interactions with marine Methylomicrobium in
      deep-water coral reef sediment off the coast of Norway.
AB  - Deep-water coral reefs are seafloor environments with diverse biological
      communities surrounded by cold permanent darkness. Sources of energy and carbon
      for the nourishment of these reefs are presently unclear. We investigated one
      aspect of the food web using DNA stable-isotope probing (DNA-SIP). Sediment from
      beneath a Lophelia pertusa reef off the coast of Norway was incubated until
      assimilation of 5 micromol 13CH4 g(-1) wet weight occurred. Extracted DNA was
      separated into 'light' and 'heavy' fractions for analysis of labelling. Bacterial
      community fingerprinting of PCR-amplified 16S rRNA gene fragments revealed two
      predominant 13C-specific bands. Sequencing of these bands indicated that carbon
      from 13CH4 had been assimilated by a Methylomicrobium and an uncultivated member
      of the Gammaproteobacteria. Cloning and sequencing of 16S rRNA genes from the
      heavy DNA, in addition to genes encoding particulate methane monooxygenase and
      methanol dehydrogenase, all linked Methylomicrobium with methane metabolism.
      Putative cross-feeders were affiliated with Methylophaga (Gammaproteobacteria),
      Hyphomicrobium (Alphaproteobacteria) and previously unrecognized methylotrophs of
      the Gammaproteobacteria, Alphaproteobacteria, Deferribacteres and Bacteroidetes.
      This first marine methane SIP study provides evidence for the presence of
      methylotrophs that participate in sediment food webs associated with deep-water
      coral reefs.

PMID- 18811652
TI  - Substrate-dependent denitrification of abundant probe-defined denitrifying
      bacteria in activated sludge.
AB  - The denitrification capacity of different phylogenetic bacterial groups was
      investigated on addition of different substrates in activated sludge from two
      nutrient-removal plants. Nitrate/nitrite consumption rates (CRs) were calculated
      from nitrate and nitrite biosensor, in situ measurements. The nitrate/nitrite CRs
      depended on the substrate added, and acetate alone or combined with other
      substrates yielded the highest rates (3-6 mg N gVSS(-1) h(-1)). The nitrate CRs
      were similar to the nitrite CRs for most substrates tested. The structure of the
      active denitrifying population was investigated using heterotrophic CO2
      microautoradiography (HetCO2-MAR) and FISH. Probe-defined denitrifiers appeared
      as specialized substrate utilizers despite acetate being preferentially used by
      most of them. Azoarcus and Accumulibacter abundance in the two different sludges
      was related to differences in their substrate-specific nitrate/nitrite CRs.
      Aquaspirillum-related bacteria were the most abundant potential denitrifiers (c.
      20% of biovolume); however, Accumulibacter (3-7%) and Azoarcus (2-13%) may have
      primarily driven denitrification by utilizing pyruvate, ethanol, and acetate.
      Activated sludge denitrification was potentially conducted by a diverse,
      versatile population including not only Betaproteobacteria (Aquaspirillum,
      Thauera, Accumulibacter, and Azoarcus) but also some Alphaproteobacteria and
      Gammaproteobacteria, as indicated by the assimilation of 14CO2 by these probe
      defined groups with a complex substrate mixture as an electron donor and nitrite
      as an electron acceptor in HetCO2-MAR-FISH tests.

PMID- 18811653
TI  - Short-term dynamics of bacterial communities in a tidally affected coastal
      ecosystem.
AB  - Tidal effects on the composition of free-living (FL) and particle-associated (PA)
      bacterial communities were studied in a tidal flat ecosystem in the southern
      North Sea. Denaturing gradient gel electrophoresis targeting the 16S rRNA gene
      and the 16S rRNA of Bacteria, Bacteroidetes, Alphaproteobacteria and the
      Roseobacter clade was applied. Despite strong tidal variations in the quantity
      and, depending on the season, also the quality of suspended matter as well as
      variations in bacterial activity, the bacterial community composition remained
      rather stable. FISH showed some variations of the community composition, but
      these were not related to typical tidal situations. Variations were higher during
      tidal cycles in May and July compared with November. Bacteroidetes, Alpha- and
      Gammaproteobacteria constituted the majority of the bacterial communities but
      relative proportions of the different groups varied considerably. On particles,
      Betaproteobacteria were also detected to substantial proportions. The Roseobacter
      clade constituted up to 90% of FL but only 30% of PA Alphaproteobacteria. Banding
      patterns of the Bacteroidetes-specific amplicons, and in particular those
      targeting the 16S rRNA, revealed tidally induced effects, as several bands
      appeared or disappeared at distinct events such as slack water or resuspension.
      Sequencing of prominent bands revealed predominantly phylotypes reported
      previously from this ecosystem.

PMID- 18811654
TI  - Activity of native vs. synthetic promoters in Brucella.
AB  - Brucellosis caused by Brucella species is reportedly the most common zoonotic
      infection worldwide. The bacterial pathogen is also classified by the Centers for
      Disease Control and Prevention as a category (B) pathogen that has the potential
      for development as a bioweapon. Although eight genomes of Brucella have been
      sequenced, little information is available regarding the regulation of gene
      expression and promoter activity in Brucella spp. We therefore constructed a set
      of broad-host-range vectors expressing the lacZ reporter gene from various
      promoters. Four groups of promoters (Brucella native, antibiotic resistant,
      bacteriophage and synthetic promoters) were tested in vivo and in vitro in
      Brucella suis. The highest level of heterologous gene expression was achieved
      with synthetic hybrid trc promoter carrying the adenine-rich upstream element.
      Furthermore, this demonstrates the usefulness of synthetic promoters for enhanced
      level of gene expression in Brucella spp.

PMID- 18811655
TI  - Epidemiological study of Vibrio cholerae using variable number of tandem repeats.
AB  - By conventional genetic methods, including pulse-field gel electrophoresis and
      multilocus sequence typing, most pathogenic, cholera toxin-positive O1 and O139
      isolates of Vibrio cholerae cannot be distinguished. We evaluated relationships
      among 173 V. cholerae isolates collected between 1992 and 2007 from different
      geographic areas in India by analyzing five variable number of tandem repeat
      (VNTR) loci. Each VNTR locus was highly variable, with between 5 and 19 alleles.
      eburst analysis revealed four large groups of genetically related isolates. Two
      groups contained genotypes of isolates with the O139 serogroup (which emerged for
      the first time in epidemic form in 1992), with the other two groups containing O1
      strains. In subsequent analysis, it was possible to track the spread of specific
      genotypes across time and space. Our data highlight the utility of the
      methodology as an epidemiologic tool for assessing spread of isolates in both
      epidemic and endemic settings.

PMID- 18811656
TI  - CagA of Helicobacter pylori alters the expression and cellular distribution of
      host proteins involved in cell signaling.
AB  - To expand our knowledge of Helicobacter pylori virulence mechanisms, we used
      iTRAQ (isobaric tagging reagents for relative and absolute quantification)-based
      proteomic analysis to investigate the effect of H. pylori on gastric AGS tissue
      culture cells. In particular, we were interested in finding out which effects of
      H. pylori were dependent on the cytotoxins CagA and VacA. Protein analysis was
      restricted to detergent-resistant membranes (DRMs), because both toxins were
      described previously to localize in lipid raft-like domains. Using H. pylori wild
      type and two isogenic mutants, DeltacagA and DeltavacA, we identified a total of
      21 proteins that were either increased or decreased in the DRMs due to bacterial
      infection. The effect on three of these proteins, ezrin, syndecan-4 and Rab11
      FIP1, were furthermore dependent on CagA. Because these proteins have been
      implicated in cell migration, adhesion and polarity, they might act as important
      mediators of CagA cytotoxicity.

PMID- 18811657
TI  - Isolation of a Poterioochromonas capable of feeding on Microcystis aeruginosa and
      degrading microcystin-LR.
AB  - Algal blooms have become a worldwide issue recently, especially those comprised
      of toxic cyanobacteria. Grazers' predation of bloom-forming algae plays an
      important role in water clearing. In this study, a species of golden alga (strain
      ZX1), capable of feeding on the toxic cyanobacteria Microcystis aeruginosa, was
      isolated and identified as Poterioochromonas sp. (GenBank accession: EU586184) on
      the basis of morphological characteristics and 18s rRNA gene sequencing. Feeding
      experiments showed that ZX1 could clear high densities of M. aeruginosa (7.3 x
      10(5)-4.3 x 10(6) cells mL(-1)) in a short time (40 h), with inhibition ratios
      higher than 99.9%. ZX1 grew during the feeding processes and achieved a maximum
      density of 10-20% of the initial M. aeruginosa density. Furthermore, this study
      is the first to report that ZX1 was able to degrade microcystin-LR (MC-LR) in
      cells of M. aeruginosa while digesting the whole cells, and that the degradation
      process was determined to be carried out inside the ZX1 cell. For a total MC-LR
      (intra- and extracellular) concentration of up to 114 microg L(-1), 82.7% was
      removed in 40 h. This study sheds light on the importance of golden alga in
      aquatic microbial ecosystems and in the natural transportation/transformation of
      MC-LR.

PMID- 18811659
TI  - Overexpression of the aldose reductase GRE3 suppresses lithium-induced galactose
      toxicity in Saccharomyces cerevisiae.
AB  - In Saccharomyces cerevisiae, lithium induces a 'galactosemia-like' phenotype as a
      consequence of inhibition of phosphoglucomutase, a key enzyme in galactose
      metabolism. Induced galactose toxicity is prevented by deletion of GAL4, which
      inhibits the transcriptional activation of genes involved in galactose metabolism
      and by deletion of the galactokinase (GAL1), indicating that galactose-1
      phosphate, a phosphorylated intermediate of the Leloir pathway, is the toxic
      compound. As an alternative to inhibiting entry and metabolism of galactose, we
      investigated whether deviation of galactose metabolism from the Leloir pathway
      would also overcome the galactosemic effect of lithium. We show that cells
      overexpressing the aldose reductase GRE3, which converts galactose to galactitol,
      are more tolerant to lithium than wild-type cells when grown in galactose medium
      and they accumulate more galactitol and less galactose-1-phosphate.
      Overexpression of GRE3 also suppressed the galactose growth defect of the
      'galactosemic'gal7- and gal10-deleted strains, which lack galactose-1-P
      uridyltransferase or UDP-galactose-4-epimerase activities, respectively.
      Furthermore, the effect of GRE3 was independent of the inositol monophosphatases
      INM1 and INM2. We propose that lithium induces a galactosemic state in yeast and
      that inhibition of the Leloir pathway before the phosphorylation step or
      stimulation of galactitol production suppresses lithium-induced galactose
      toxicity.

PMID- 18811660
TI  - Reproductive conflict delays the recovery of an endangered social species.
AB  - 1. Evolutionary theory predicts that individuals, in order to increase their
      relative fitness, can evolve behaviours that are detrimental for the group or
      population. This mismatch is particularly visible in social organisms. Despite
      its potential to affect the population dynamics of social animals, this principle
      has not yet been applied to real-life conservation. 2. Social group structure has
      been argued to stabilize population dynamics due to the buffering effects of
      nonreproducing subordinates. However, competition for breeding positions in such
      species can also interfere with the reproduction of breeding pairs. 3. Seychelles
      magpie robins, Copsychus sechellarum, live in social groups where subordinate
      individuals do not breed. Analysis of long-term individual-based data and short
      term behavioural observations show that subordinates increase the territorial
      takeover frequency of established breeders. Such takeovers delay offspring
      production and decrease territory productivity. 4. Individual-based simulations
      of the Seychelles magpie robin population parameterized with the long-term data
      show that this process has significantly postponed the recovery of the species
      from the Critically Endangered status. 5. Social conflict thus can extend the
      period of high extinction risk, which we show to have population consequences
      that should be taken into account in management programmes. This is the first
      quantitative assessment of the effects of social conflict on conservation.

PMID- 18811658
TI  - Magnificent seven: roles of G protein-coupled receptors in extracellular sensing
      in fungi.
AB  - G protein-coupled receptors (GPCRs) represent the largest family of transmembrane
      receptors and are responsible for transducing extracellular signals into
      intracellular responses that involve complex intracellular-signaling networks.
      This review highlights recent research advances in fungal GPCRs, including
      classification, extracellular sensing, and G protein-signaling regulation. The
      involvement of GPCRs in pheromone and nutrient sensing has been studied
      extensively over the past decade. Following recent advances in fungal genome
      sequencing projects, a panoply of GPCR candidates has been revealed and some have
      been documented to play key roles sensing diverse extracellular signals, such as
      pheromones, sugars, amino acids, nitrogen sources, and even photons.
      Identification and deorphanization of additional putative GPCRs may require the
      development of new research tools. Here, we compare research on GPCRs in fungi
      with information derived from mammalian systems to provide a useful road map on
      how to better understand ligand-GPCR-G protein interactions in general. We also
      emphasize the utility of yeast as a discovery tool for systemic studies of GPCRs
      from other organisms.

PMID- 18811661
TI  - Climate effects on offspring sex ratio in a viviparous lizard.
AB  - 1. Understanding individual and population responses to climate change is
      emerging as an important challenge. Because many phenotypic traits are sensitive
      to environmental conditions, directional climate change could significantly alter
      trait distribution within populations and may generate an evolutionary response.
      2. In species with environment-dependent sex determination, climate change may
      lead to skewed sex ratios at hatching or birth. However, there are virtually no
      empirical data on the putative link between climatic parameters and sex ratios
      from natural populations. 3. We monitored a natural population of viviparous
      lizards with temperature-dependent sex determination (Niveoscincus ocellatus)
      over seven field seasons. Sex ratios at birth fluctuated significantly among
      years and closely tracked thermal conditions in the field, with the proportion of
      male offspring increasing in colder years. 4. This is the first study to
      demonstrate the effect of local climatic conditions (e.g. temperature) on
      offspring sex ratio fluctuations in a free-living population of a viviparous
      ectotherm. A succession of warmer-than-usual years (as predicted under many
      climate-change scenarios) likely would generate female-biased sex ratios at
      birth, while an increase in interannual variation (as also predicted under
      climate change scenarios) could lead to significant fluctuations in cohort sex
      ratios. If cohort sex ratio bias at birth leads to adult sex ratio bias, long
      term directional changes in thermal conditions may have important effects on
      population dynamics in this species.

PMID- 18811662
TI  - Male sterility, fitness gain curves and the evolution of gender specialization
      from distyly in Erythroxylum havanense.
AB  - The evolution of dioecy from a monomorphic hermaphroditic condition requires two
      mutations, one producing females and one producing males. Conversely, a single
      mutation sterilizing one sexual function in one morph of distylous species would
      result in functional dioecy because such a mutation also affects the
      complementary function in the other morph. In this study, we tested these ideas
      with Erythroxylum havanense, a distylous species with morph-biased male
      sterility. Based on sex allocation theory we evaluated whether the invasion of
      thrum females is favoured over the maintenance of this morph cosexuals.
      Completely male sterile thrum plants obtained higher fitness returns than
      hermaphrodites or partial male sterile individuals of the same morph, thus
      favouring the invasion of female thrum plants. We concluded that because fruit
      production of pin individuals depends on the pollen produced by thrum plants, the
      invasion of thrum females would result on the evolution of functional dioecy.

PMID- 18811663
TI  - Nice natives and mean migrants: the evolution of dispersal-dependent social
      behaviour in viscous populations.
AB  - There has been much interest in the evolution of social behaviour in viscous
      populations. While low dispersal increases the relatedness of neighbours, which
      tends to promote the evolution of indiscriminate helping behaviour, it can also
      increase competition between neighbours, which tends to inhibit the evolution of
      helping and may even favour harming behaviour. In the simplest scenario, these
      two effects exactly cancel, so that dispersal rate has no impact on the evolution
      of helping or harming. Here, we show that dispersal rate does matter when
      individuals can adjust their social behaviour conditional on whether they have
      dispersed or whether they have remained close to their place of origin. We find
      that nondispersing individuals are weakly favoured to indiscriminately help their
      neighbours, whereas dispersing individuals are more readily favoured to
      indiscriminately harm their neighbours.

PMID- 18811664
TI  - The frequency of multiple paternity predicts variation in testes size among
      island populations of house mice.
AB  - Polyandry generates selection on males through sperm competition, which has broad
      implications for the evolution of ejaculates and male reproductive anatomy.
      Comparative analyses across species and competitive mating trials within species
      have suggested that sperm competition can influence the evolution of testes size,
      sperm production and sperm form and function. Surprisingly, the intraspecific
      approach of comparing among population variation for investigating the selective
      potential of sperm competition has rarely been explored. We sampled seven island
      populations of house mice and determined the frequency of multiple paternity
      within each population. Applying the frequency of multiple paternity as an index
      of the risk of sperm competition, we looked for selective responses in male
      reproductive traits. We found that the risk of sperm competition predicted testes
      size across the seven island populations of house mice. However, variation in
      sperm traits was not explained by sperm competition risk. We discuss these
      findings in relation to sperm competition theory, and other intrinsic and
      extrinsic factors that might influence ejaculate quality.

PMID- 18811665
TI  - Hybrid breakdown and mitochondrial dysfunction in hybrids of Nasonia parasitoid
      wasps.
AB  - Male F(2) hybrids of the wasps Nasonia giraulti and Nasonia vitripennis suffer
      increased mortality during development. Previous studies suggested that the
      mitochondria may play an important role in this pattern of hybrid breakdown. The
      mitochondrial genome encodes 13 polypeptides, which are integral subunits of the
      oxidative phosphorylation enzyme complexes I, III, IV and V. We show that the
      mitochondrial ATP production rate and the efficacy of the enzyme complexes I, III
      and IV, but not that of the completely nuclear-encoded complex II, are reduced in
      F(2) hybrid males of N. giraulti and N. vitripennis. We hypothesize that nuclear
      mitochondrial protein interactions in the oxidative phosphorylation pathway are
      disrupted in these hybrids, reducing energy generation capacity and potentially
      reducing hybrid fitness. Our results suggest that dysfunctional cytonuclear
      interactions could represent an under-appreciated post-zygotic isolation
      mechanism that, due to elevated evolutionary rates of mitochondrial genes,
      evolves very early in the speciation process.

PMID- 18811666
TI  - Investigating latitudinal clines for life history and stress resistance traits in
      Drosophila simulans from eastern Australia.
AB  - Latitudinal clines have been demonstrated for many quantitative traits in
      Drosophila and are assumed to be due to climatic selection. However, clinal
      studies are often performed in species of Drosophila that contain common
      cosmopolitan inversion polymorphisms that also show clinal patterns. These
      inversion polymorphisms may be responsible for much of the observed clinal
      variation. Here, we consider latitudinal clines for quantitative traits in
      Drosophila simulans from eastern Australia. Drosophila simulans does not contain
      cosmopolitan inversion polymorphisms, so allows the study of clinal selection on
      quantitative traits that are not confounded by associations with inversions. Body
      size showed a strong linear cline for both females and males. Starvation
      resistance exhibited a weak linear cline in females, whereas chill-coma recovery
      exhibited a significant nonlinear cline in females only. No clinal pattern was
      evident for development time, male chill-coma recovery, desiccation or heat
      resistance. We discuss these results with reference to the role inversion
      polymorphisms play in generating clines in quantitative traits of Drosophila.

PMID- 18811667
TI  - Selection on floral and carbon uptake traits of Lobelia siphilitica is similar in
      females and hermaphrodites.
AB  - Sexual dimorphism is common in plants and animals. Although this dimorphism is
      often assumed to be adaptive, natural selection has rarely been measured on
      sexually dimorphic traits of plants. We measured phenotypic selection via seed
      set on two floral and four carbon uptake traits of female and hermaphrodite
      Lobelia siphilitica. Because females can reproduce only via seeds, which are
      costlier than pollen, we predicted that females with smaller flowers and enhanced
      carbon uptake would have higher fitness, resulting in either sex morph-specific
      directional selection or stabilizing selection for different optimal trait values
      in females and hermaphrodites. We found that directional selection on one carbon
      uptake trait differed between females and hermaphrodites. We did not detect
      significant stabilizing selection on traits of either sex morph. Our results
      provide little support for the hypothesis that sexual dimorphism in gynodioecious
      plants evolved in response to sex morph-specific selection.

PMID- 18811668
TI  - Divergence in parental care, habitat selection and larval life history between
      two species of Peruvian poison frogs: an experimental analysis.
AB  - Changes in the nature of the ecological resources exploited by a species can lead
      to the evolution of novel suites of behaviours. We identified a case in which the
      transition from large pool use to the use of very small breeding pools in
      neotropical poison frogs (family Dendrobatidae) is associated with the evolution
      of a suite of behaviours, including biparental care (from uniparental care) and
      social monogamy (from promiscuity). We manipulated breeding pool size in order to
      demonstrate experimentally that breeding habitat selection strategy has evolved
      in concert with changes in parental care and mating system. We also manipulated
      intra- and interspecific larval interactions to demonstrate that larval
      adaptation to the use of very small pools for breeding affected the evolution of
      larval competition and cannibalism. Our results illustrate the intimate
      connection between breeding pool ecology, parental care and mating strategies in
      Peruvian poison frogs.

PMID- 18811669
TI  - Leukoencephalopathy with anterior temporal cysts due to congenital CMV infection
      diagnosed retrospectively.
AB  - Leukoencephalopathy with subcortical cysts has been described in a variety of
      conditions. However, few reports have highlighted congenital CMV as a cause of
      this imaging finding. We report a 1-year-old girl with developmental delay and
      sensorineural hearing loss whose MRI brain showed abnormal white matter and
      temporal cysts. Congenital CMV infection was diagnosed retrospectively by
      examination of dried blood spot from the newborn screening card.

PMID- 18811670
TI  - Isolated temporal lobe involvement in Japanese encephalitis.
AB  - Temporal lobe involvement on neuroimaging is extremely rare in Japanese
      encephalitis (JE) and isolated temporal lobe involvement on neuroimaging has
      rarely been described in the literature. With isolated temporal lobe involvement,
      distinguishing JE from the treatable Herpes simplex encephalitis (HSE) can be
      difficult. Both JE and HSE should be considered in patients who present
      clinically with acute encephalitis and have radiological evidence of temporal
      lobe involvement, especially in JE endemic areas.

PMID- 18811671
TI  - Signaling pathways for induction of platelet aggregation by SAS tongue cancer
      cells--a mechanism of hematogenous metastasis.
AB  - BACKGROUND: Tongue cancer metastasis is mainly through blood stream and possibly
      associated with tumor cell-induced platelet aggregation (TCIPA). METHODS:
      Platelet aggregation was induced by different amounts of SAS tongue cancer cells
      with/without inhibitors and the latent period for induction of platelet
      aggregation was recorded. Gene expression was analyzed by reverse transcriptase
      polymerase chain reaction. RESULTS: SAS cells (4 x 10(4) to 1 x 10(6) cells/ml)
      induced platelet aggregation in a cell density-dependent manner. The latent
      period for induction of platelet aggregation reduced from 11.3 min (2 x 10(5)
      cells/ml) to 0.9 min (5 x 10(5) cells/ml). The extent of platelet aggregation
      increased from 39% to 76% by 2 x 10(5) and 5 x 10(5) SAS cells. Pre-treatment of
      SAS cells with aspirin showed little effect on its induction of platelet
      aggregation. SAS cells expressed tissue factor (TF) mRNA and the SAS cells
      induced TCIPA was inhibited by TF neutralization antibody (5-20 microg/ml),
      heparin (5-10 U/ml), Hirudin fragment 54-65 (50 microg/ml) and D-Phenylalanyl-L
      prolyl-L-arginine chloromethyl ketone. But areca nut (AN, a betel quid component
      known to generate reactive oxygen species (ROS)) extract showed little effect on
      TF expression in SAS cells. Pre-treatment with U73122 and 2
      aminoethoxydiphenylborate inhibited SAS-induced TCIPA. Interestingly, catalase
      suppressed SAS cells-induced TCIPA, whereas AN extract enhanced this event.
      CONCLUSIONS: These results suggest that tongue cancer cells may induce TCIPA and
      enhance tumor metastasis. SAS-induced TCIPA is related to TF secretion, thrombin
      generation and associated with Phospholipase C-Inositol triphosphate signaling
      and ROS production. Betel quid chewing may potentially promote tongue cancer
      metastasis.

PMID- 18811672
TI  - Campylobacter monitoring in German broiler flocks: an explorative time series
      analysis.
AB  - Campylobacter, a major zoonotic pathogen, displays seasonality in poultry and in
      humans. In order to identify temporal patterns in the prevalence of thermophilic
      Campylobacter spp. in a voluntary monitoring programme in broiler flocks in
      Germany and in the reported human incidence, time series methods were used. The
      data originated between May 2004 and June 2007. By the use of seasonal
      decomposition, autocorrelation and cross-correlation functions, it could be shown
      that an annual seasonality is present. However, the peak month differs between
      sample submission, prevalence in broilers and human incidence. Strikingly, the
      peak in human campylobacterioses preceded the peak in broiler prevalence in Lower
      Saxony rather than occurring after it. Significant cross-correlations between
      monthly temperature and prevalence in broilers as well as between human
      incidence, monthly temperature, rainfall and wind-force were identified. The
      results highlight the necessity to quantify the transmission of Campylobacter
      from broiler to humans and to include climatic factors in order to gain further
      insight into the epidemiology of this zoonotic disease.

PMID- 18811673
TI  - Seroprevalence of Toxoplasma gondii among Nunavik Inuit (Canada).
AB  - As a result of their intimate contact with the land and their nutritional habits,
      the Inuit of Nunavik are considered to be at risk from zoonotic infections. To
      better understand the risk factors for Toxoplasma gondii infection, a serosurvey
      was conducted in Nunavik, Quebec, in September 2004. A representative sample of
      the Inuit adult population of Nunavik participated in this cross-sectional study
      (n = 917). Antibodies (IgG) against T. gondii were detected by immunoassay.
      Information on sociodemographic characteristics, traditional activities, domestic
      environment and nutrition was gathered by questionnaire and explored as variables
      explanatory of seropositive results. Associations found to be statistically
      significant in univariate analyses were assessed by multivariable logistic
      regression to control for confounding factors. Almost two thirds (59.8%) of the
      Inuit of Nunavik were found to be seropositive for T. gondii. In multivariate
      analyses, risk factors for seropositivity were: increasing age, gender (women >
      men), lower level of education, consumption of potentially contaminated water
      (determined by an index of risk from waterborne infections), frequent cleaning of
      water reservoirs, and consumption of seal meat and feathered game. There was some
      variation in seroprevalence between the Ungava Bay coast (52.3%) and the Hudson
      Bay coast (65.6%), the two main regions of Nunavik, but this variation was not
      significant in the multivariable logistic regression model. This cross-sectional
      study demonstrated high T. gondii seroprevalence in the Inuit population and
      revealed that age, gender, schooling and community of residence all influence
      serostatus in this population. Variables related to drinking water and food
      choices may also influence the risk of infection. These results raise important
      questions about T. gondii transmission in Nunavik including possible links
      between terrestrial and marine cycles.

PMID- 18811674
TI  - Human brucellosis: seroprevalence and risk factors related to high risk
      occupational groups in Tanga Municipality, Tanzania.
AB  - The objective of this study was to describe the prevalence of brucellosis in
      various occupations in Tanga, Tanzania. During the year 2004, serum samples were
      collected from volunteers in various occupations and screened for brucella
      antibodies using Rose Bengal Plate Agglutination Test. Information on occupation,
      kind of work and contacts with livestock was collected and age and sex were
      recorded. The overall sero prevalence of antibodies to Brucella abortus was
      5.52%. One variable in a multivariate regression model was significantly
      associated with seropositivity to B. abortus: abattoir workers. The prevalence of
      antibody was significantly higher (P < 0.05) among personnel employed in high
      risk jobs such as cutting animal throats and cleaning slaughtered animals parts.
      None of the other factors investigated was associated with seropositivity to B.
      abortus. This study documents the serological evidence of B. abortus infection
      for the first time in abattoir workers in Tanzania.

PMID- 18811675
TI  - Prevention of shedding and re-shedding of Toxoplasma gondii oocysts in
      experimentally infected cats treated with oral Clindamycin: a preliminary study.
AB  - This work aimed to evaluate the effects of preventive oral Clindamycin in cats
      infected with Toxoplasma gondii. Twelve short hair cats were divided into two
      groups (group 1 and group 2). No titres of T. gondii antibodies were detected in
      these cats before the experiment. The animals from group 1 were infected with
      tissue cysts of T. gondii and group 2 were infected and treated with Clindamycin
      (20 mg/kg/day). The infection was done with almost 40-50 tissue cysts for each
      cat on day 0. The cats from group 2 were treated with Clindamycin by oral rout
      for 24 days (from day -3 to day 21). At day 45, the groups 1 and 2 were divided
      into two subgroups with three animals each. Subgroups 1A and 2A were
      immunosuppressed with dexamethasone (1 mg/kg/day) for30 days and subgroups 1B and
      2B were not immunosuppressed. Faecal exam looking for oocyst shedding was made by
      30 days after T. gondii infection, and for 30 days after immunosuppression. All
      kittens from group 1 shedding oocysts after infection, while animals from group 2
      did not shed. After immunosuppression period, all animals from group 1A re-shed
      oocysts and animals from group 2A remained without shed. However, 2 (66.6%) of
      the kittens from subgroup 2B shed oocysts 19-20 days after re-challenge. Based on
      this preliminary study, Clindamycin had a complete inhibitory effect on shedding
      of oocysts by cats, even under severe immunosuppression, which is a new finding
      not reported elsewhere.

PMID- 18811676
TI  - Campylobacter spp. and their antimicrobial resistance patterns in poultry: an
      epidemiological survey study in Turkey.
AB  - The current study aimed at determining the prevalence and the antimicrobial
      resistance profiles of thermophilic Campylobacter spp. infecting broiler
      chickens. A total of 240 caecal samples from six slaughterhouses were examined
      for the presence of Campylobacter spp. C. jejuni was detected in 40.4% (97/240)
      of the samples and C. coli in 12.1% (29/240). The agar disc diffusion method and
      the E-test were used for testing the antimicrobial susceptibility of C. jejuni
      and C. coli isolates. C. jejuni isolates were most resistant to nalidixic acid
      (79.4%) followed by tetracycline (76.3%), ciprofloxacin (74.2%) and enrofloxacin
      (15.5%). Among the C. coli isolates, the frequency of resistance to nalidixic
      acid and ciprofloxacin was the same at 65.5%. The predominant profiles of
      multidrug resistance to three or more antimicrobials in C. jejuni and C. coli
      were determined as tetracycline/nalidixic acid/ciprofloxacin resistance (48.5%)
      and tetracycline/nalidixic acid/ciprofloxacin/enrofloxacin resistance (51.7%),
      respectively. To prevent the transmission of antimicrobial-resistant bacteria of
      animal origin to humans, it should be noted that high proportions of multidrug
      resistance were found in both species.

PMID- 18811677
TI  - Trolox down-regulates transforming growth factor-beta and prevents experimental
      cirrhosis.
AB  - Cirrhosis is a very common disease and its treatment is limited due to lack of
      effective drugs. Some studies indicate that this disease is associated with
      oxidative stress. Therefore, we decided to study the effect of trolox, an
      effective antioxidant, on experimental cirrhosis. Cirrhosis was induced by CCl4
      administration (0.4 g/kg, intraperitoneally, three times per week, for 8 weeks)
      to Wistar male rats. Trolox was administered daily (50 mg/kg, orally). Fibrosis
      was assessed histologically and by measuring liver hydroxyproline content.
      Glutathione, lipid peroxidation and glycogen were measured in liver; serum
      markers of liver damage were also quantified. Transforming growth factor-beta
      (TGF-beta) was determined by Western blot and quantified densitometrically.
      Alkaline phosphatase, gamma-glutamyl transpeptidase and alanine aminotransferase
      increased in the group receiving CCl4; trolox completely or partially prevented
      these alterations. Glycogen was almost depleted by CCl4 but was partially
      preserved by trolox. Lipid peroxidation increased while glutathione decreased by
      CCl4 administration; trolox corrected both effects. Histology showed thick bands
      of collagen, necrosis and distortion of the hepatic parenchyma in the CCl4 group,
      such effects were prevented by trolox. Hydroxyproline content increased 5-fold by
      CCl4, while the group receiving both CCl4 and trolox showed no significant
      difference compared to the control group. CCl4 increased 3-fold TGF-beta, while
      trolox completely prevented this increase. We found that trolox effectively
      prevented cirrhosis induced with CCl4 in the rat. Our results suggest that the
      beneficial effects of trolox may be associated to its antioxidant properties and
      to its ability to reduce the profibrogenic cytokine TGF-beta expression.

PMID- 18811679
TI  - The P300 event-related potential and its possible role as an endophenotype for
      studying substance use disorders: a review.
AB  - The concept of endophenotypes has gained popularity in recent years. This is
      because of the potential that endophenotypes provide of measuring objective trait
      markers that are simpler to access and assess than complex behavioral disease
      phenotypes themselves. The simplicity, ease of measurement and the putative links
      to the etiology of the disease in the study of an endophenotype has the potential
      promise of unraveling the genetic basis of the disease in question. Of the
      various proposed endophenotypes, the P300 component of the event-related
      potential has been used in studies on alcoholism, schizophrenia and externalizing
      disorders. The current state of knowledge regarding the concept of
      endophenotypes, P300 and the validity of P300 as an endophenotype with special
      reference to substance use disorders is discussed in this review. The
      implications of the above are discussed.

PMID- 18811678
TI  - Norepinephrine and stimulant addiction.
AB  - No pharmacotherapies are approved for stimulant use disorders, which are an
      important public health problem. Stimulants increase synaptic levels of the
      monoamines dopamine (DA), serotonin and norepinephrine (NE). Stimulant reward is
      attributable mostly to increased DA in the reward circuitry, although DA
      stimulation alone cannot explain the rewarding effects of stimulants. The
      noradrenergic system, which uses NE as the main chemical messenger, serves
      multiple brain functions including arousal, attention, mood, learning, memory and
      stress response. In pre-clinical models of addiction, NE is critically involved
      in mediating stimulant effects including sensitization, drug discrimination and
      reinstatement of drug seeking. In clinical studies, adrenergic blockers have
      shown promise as treatments for cocaine abuse and dependence, especially in
      patients experiencing severe withdrawal symptoms. Disulfiram, which blocks NE
      synthesis, increased the number of cocaine-negative urines in five randomized
      clinical trials. Lofexidine, an alpha(2)-adrenergic agonist, reduces the craving
      induced by stress and drug cues in drug users. In addition, the NE transporter
      (NET) inhibitor atomoxetine attenuates some of d-amphetamine's subjective and
      physiological effects in humans. These findings warrant further studies
      evaluating noradrenergic medications as treatments for stimulant addiction.

PMID- 18811680
TI  - Chronic viral hepatitis is a significant contributor to the immunosenescent
      phenotype of parenteral drug addiction.
AB  - Intravenous drug addiction is known to be associated with an inordinate morbidity
      and mortality. As our previous report had identified an immune phenotype
      consistent with accelerated ageing, we wished to investigate how much of this
      change may have been related to chronic viral hepatitis. A total of 12 409
      clinical pathology results from the period 1995-2007 were reviewed. To control
      for the differences in age, only patients less than 48 years of age were
      considered. A total of 636 substance use disorder (SUD) and 6103 non-SUD (N-SUD)
      patients were studied. They had comparable ages (mean +/- SD 31.32 +/- 6.90
      versus 31.57 +/- 9.23, P-value not significant), but the SUD group had more males
      (74.37% versus 53.20%, P < 0.001). For most of the changes examined splitting the
      two SUD groups into hepatitis C positive (HCV+) and hepatitis C negative (HCV-)
      demonstrated that the majority of the described changes were most marked in the
      HCV+ group. The globulins were higher in the HCV+ group and the albumin was lower
      and fell more markedly with age than in N-SUD or HCV- (all P < 0.001). The
      globulin/albumin ratio was significantly higher in HCV+ than HCV- or N-SUD (both
      P < 0.0001) and rose more with age. These changes were paralleled by the ESR,
      elevations in the CRP and lymphocyte count. Transaminases were elevated in SUD
      and HCV+ groups compared with N-SUD (all P < 0.02). At multivariate analysis ESR,
      lymphocyte count, dual hepatitis B and C seropositivity, AST and HCVAb were
      significant predictors of the serum globulin level and accounted for 21% of the
      variance. These data extend our earlier report and show that much of the
      immunosenescent phenotype of SUD, encompassing the known immunosuppression and
      the observed immunostimulation, is statistically related to chronic viral
      hepatitis. Important theoretical and practical management (vaccination)
      implications ensue.

PMID- 18811681
TI  - Elevated free thyroxin levels following low molecular weight heparin treatment in
      a premature neonate.

PMID- 18811682
TI  - Thresholds, dose-response relationships and dose metrics in allergic contact
      dermatitis.

PMID- 18811683
TI  - Prediction of chemical absorption into and through the skin from cosmetic and
      dermatological formulations.
AB  - BACKGROUND: To date, risk assessment following topical exposure to
      cosmetic/dermatological formulations cannot be precisely evaluated. OBJECTIVES:
      To provide a tool for optimization of active permeation into/through skin and for
      risk assessment. METHODS: A predictive model was developed for estimating the
      cumulative mass of a chemical absorbed into and across the skin from a
      cosmetic/dermatological formulation. Account was taken of (i) the ionization
      state of the chemical, to correct the skin/vehicle partition coefficient; and
      (ii) the nature of the cosmetic/dermatological formulation. Three specific
      assumptions were made: firstly, steady-state transport across the skin was
      achieved despite application of a finite dose of chemical; secondly, vehicle
      effects were small relative to the precision of the prediction; and, thirdly,
      each formulation could be treated as an oil-in-water emulsion, in which only that
      fraction of the chemical in the aqueous phase was available to partition into the
      stratum corneum. A database of 101 ex vivo human skin experiments involving 36
      chemicals was analysed. RESULTS: For 91% of the data, the difference between
      predicted and experimental values was less than a factor 5; when the
      aforementioned corrections were not used, on the other hand, only 26% of the data
      was well predicted. The model was successfully applied to predict skin absorption
      of two compounds not included in the database, for which in vitro percutaneous
      penetration from cosmetic vehicles have been measured. CONCLUSION: A model has
      been developed to predict the mass of a chemical absorbed into and through the
      skin from a cosmetic or dermatological formulation.

PMID- 18811684
TI  - Mechanism of tyrosinase inhibition by deoxyArbutin and its second-generation
      derivatives.
AB  - BACKGROUND: Disorders, such as age spots, melasma and hyperpigmentation at sites
      of actinic damage, emanate from the augmentation of an increased amount of
      epidermal melanin. OBJECTIVES: The ineptness of current therapies in treating
      these conditions, as well as high cytotoxicity, mutagenicity, poor skin
      penetration and low stability of skin-depigmenting formulations led us to
      investigate new compounds that meet the medical requirements for depigmentation
      agents. We have shown previously that the tyrosinase inhibitor deoxyArbutin (dA)
      is a more effective and less toxic skin lightener than hydroquinone (HQ).
      METHODS: The efficacy and reversibility of dA and its derivatives on inhibiting
      tyrosine hydroxylase and DOPAoxidase was assessed using standard assays. RESULTS:
      dA and its second-generation derivatives inhibit tyrosine hydroxylase and
      DOPAoxidase activities of tyrosinase dose dependently thereby inhibiting melanin
      synthesis in intact melanocytes, when used at concentrations that retain 95% cell
      viability in culture. This depigmenting effect was completely reversible when the
      compounds were removed. Tyrosinase inhibition was also observed in vitro when
      tested using human and purified mushroom tyrosinase, establishing that they are
      direct enzyme inhibitors. Lineweaver-Burk reciprocal plot analysis using mushroom
      tyrosinase illustrated that dA and its derivatives are more robust competitive
      inhibitors than HQ, when tyrosine is used as substrate. CONCLUSIONS: Thus, dA and
      its second-generation derivatives, which inhibit melanogenesis at safe
      concentrations by specifically acting on the tyrosinase enzyme at a post
      translational level, are promising agents to ameliorate hyperpigmented lesions or
      lighten skin.

PMID- 18811685
TI  - Sweat antigen induces histamine release from basophils of patients with
      cholinergic urticaria associated with atopic diathesis.
AB  - BACKGROUND: We previously demonstrated that the semipurified human sweat antigen
      causes skin reactions and histamine release from basophils via specific IgE in
      patients with atopic dermatitis (AD). Patients with cholinergic urticaria (ChU)
      also develop skin reactions and histamine release of basophils in response to
      autologous sweat. OBJECTIVES: To study whether or not patients with ChU share
      sensitivity for the sweat antigen with patients with AD and to study the clinical
      characteristics among patients with ChU and the relationship with histamine
      release activity of basophils. METHODS: The sweat antigen that induces histamine
      release from basophils of patients with AD was prepared by Con-A, anion-exchange
      and reverse-phase chromatography. Relationships between histamine-release
      activity against the sweat antigen and clinical features of patients with ChU
      were analysed. RESULTS: Twenty-three of 35 patients with ChU showed > 5% net
      histamine release in response to the semipurified sweat antigen, whereas none of
      healthy controls did so. In patients with ChU, histamine release in response to
      semipurified sweat antigen significantly correlated with the level of serum IgE
      and eosinophil numbers in peripheral blood. Incidence of each atopic disease in
      patients with ChU tended to be higher than in the general Japanese population.
      When the patients were categorized according to their responses in the histamine
      release test, the positive group tended to show a higher incidence of AD and
      bronchial asthma compared with the negative group. CONCLUSIONS: ChU and AD may
      share hypersensitivity to common antigens in sweat. The sweat allergy and atopic
      diathesis are associated with each other.

PMID- 18811686
TI  - Risk of herpes zoster infection in patients with pemphigus on mycophenolate
      mofetil.

PMID- 18811687
TI  - Occupational skin exposure to water: a population-based study.
AB  - BACKGROUND: Occupational exposure to skin irritants, in particular to water, is
      an important risk factor for hand eczema. OBJECTIVES: To assess occupational skin
      exposure to water in the general population. METHODS: As part of a public health
      survey in Stockholm, Sweden, 18,267 gainfully employed individuals aged 18-64
      years completed a questionnaire with previously validated questions regarding
      occupational skin exposure to water. RESULTS: Altogether 16% reported exposure to
      water for (1/2) h or more a day, and 13% reported exposure to water more than 10
      times a day. Furthermore, 7% reported water exposure of more than 2 h and 6% of
      more than 20 times a day. Women reported more water exposure than men and many
      female-dominated occupations were seen to comprise water exposure. Women were
      also more exposed than men within the same jobs. Young adults were more exposed
      than older. A total of 18% were employed in high-risk occupations for hand
      eczema. Fifty-nine per cent of individuals employed in high-risk occupations
      reported water exposure at work, compared with 11% in low-risk occupations.
      CONCLUSIONS: A total of 20% of the population of working age acknowledged
      occupational skin exposure to water, which was found to be more common in young
      adults and women. Using job title as a proxy for water exposure gives an
      underestimation due to misclassification. In assessing occupational skin exposure
      to water, both exposure time and frequency should be considered.

PMID- 18811688
TI  - Great Ormond Street Hospital for Children Registry for congenital melanocytic
      naevi: prospective study 1988-2007. Part 1-epidemiology, phenotype and outcomes.
AB  - BACKGROUND: The aetiology of congenital melanocytic naevi (CMNs) is unknown.
      OBJECTIVES: To identify potential aetiological factors in families of children
      with CMNs, and to relate these to long-term outcome measures. METHODS: Three
      hundred and forty-nine CMN families completed questionnaires about pregnancy and
      parental factors, and yearly questionnaires on the health of their child and
      details of the CMN. Seventy-nine control families completed one set of
      questionnaires, excluding CMN details. RESULTS: The mean prospective follow-up of
      301 CMN families was 9.2 years, median 8.9 years, total 2679 years. Forty per
      cent of patients had CMNs > 20 cm projected adult size (PAS) or multiple CMNs.
      Twenty per cent of patients had abnormal neurodevelopment and although this was
      positively associated with PAS it was seen across all size categories. The rate
      of malignant melanoma was 1.4%. This was strongly associated with PAS with all
      five cases in patients with CMNs > 60 cm PAS/multiple CMNs (rate in that group
      14%). Twenty-five per cent of CMN patients had a positive family history of a CMN
      in a second-degree relative (FHCMN). This group had a significantly different
      gender ratio, suggesting a different underlying mutation. Maternal FHCMN was
      negatively associated with PAS and satellites at birth, and maternal freckling
      was negatively associated with PAS. Other factors found to be significantly
      increased in CMN families compared with controls were maternal smoking and ill
      health during pregnancy. Maternal smoking was positively associated with PAS.
      CONCLUSIONS: This study relies on data from families after they have had a child
      with a CMN, and therefore may be subject to recall bias. Despite this, it
      contributes significantly to the knowledge of epidemiology of CMNs, and provides
      some important clues to the genetic basis of the condition.

PMID- 18811689
TI  - Expression of 25-hydroxyvitamin D3-1alpha-hydroxylase in subcutaneous fat
      necrosis.
AB  - BACKGROUND: The most serious complication of subcutaneous fat necrosis (SCFN), a
      rare condition of the newborn characterized by indurated purple nodules, is
      hypercalcaemia. However, the mechanism for this hypercalcaemia remains unclear.
      OBJECTIVES: To determine whether the hypercalcaemia associated with SCFN involves
      expression of the vitamin D-activating enzyme 25-hydroxyvitamin D(3)-1alpha
      hydroxylase (1alpha-hydroxylase) in affected tissue. METHODS: Skin biopsies from
      two male patients with SCFN and hypercalcaemia were taken. The histological
      specimens were assessed using a polyclonal antibody against 1alpha-hydroxylase.
      RESULTS: Histology in both cases showed strong expression of 1alpha-hydroxylase
      protein (brown staining) within the inflammatory infiltrate associated with SCFN.
      This was consistent with similar experiments in other granulomatous conditions.
      CONCLUSIONS: Hypercalcaemia in SCFN appears to be due to abundant levels of
      1alpha-hydroxylase in immune infiltrates associated with tissue lesions. This is
      consistent with previous observations of extrarenal 1alpha-hydroxylase in skin
      from other granulomatous conditions such as sarcoidosis and slack skin disease.

PMID- 18811690
TI  - Frontal fibrosing alopecia: clinical presentations and prognosis.
AB  - BACKGROUND: Frontal fibrosing alopecia is an uncommon condition characterized by
      progressive frontotemporal recession due to inflammatory destruction of hair
      follicles. Little is known about the natural history of this disease. OBJECTIVES:
      To determine the clinical features and natural history of frontal fibrosing
      alopecia. METHODS: We studied the cases notes of patients diagnosed with frontal
      fibrosing alopecia from 1993 to 2008 at the Royal Hallamshire Hospital,
      Sheffield. RESULTS: There were 18 patients aged between 34 and 71 years. Three
      were premenopausal. All had frontotemporal recession with scarring. This was
      associated with partial or complete loss of eyebrows in 15 patients while four
      had hair loss at other sites. One had keratosis pilaris-like papules on the face,
      and one had follicular erythema on the cheeks. Three patients had oral lichen
      planus, of whom two also had cutaneous lichen planus affecting other sites of the
      body. Treatments given included intralesional triamcinolone acetonide, 0.1%
      tacrolimus ointment and oral hydroxychloroquine. Progression of frontotemporal
      recession was seen in some patients, but not all. In one patient the hair line
      receded by 30 mm over 72 months, whereas in another patient there was no
      positional change in the hair line after 15 years. CONCLUSIONS: Frontal fibrosing
      alopecia is more common in postmenopausal women, but it can occur in younger
      women. It may be associated with mucocutaneous lichen planus. Recession of the
      hair line may progress inexorably over many years but this is not inevitable. It
      is not clear whether or not treatment alters the natural history of the disease -
      the disease stabilized with time in most of the patients with or without
      continuing treatment.

PMID- 18811691
TI  - Cicatricial marginal alopecia: is it all traction?
AB  - BACKGROUND: In a specialized hair loss clinic, a group of patients was identified
      with focal or complete hair loss at the scalp periphery, with a normal scalp
      surface. Biopsy revealed complete loss of individual hair follicles, indicative
      of scarring alopecia. Not all patients had a history supportive of a diagnosis of
      traction alopecia. OBJECTIVES: To identify and characterize further patients with
      scarring alopecia of the scalp margin using a retrospective review. METHODS: All
      biopsies of scarring alopecia carried out by a single clinician between 1 January
      1999 and 29 September 2006 were reviewed. Patients in whom the hair loss was
      located at the periphery of the scalp were selected for retrospective chart
      review. RESULTS: A total of 15 patients met the study criteria, which included
      histological scarring alopecia and hair loss of the scalp margin. Six of the
      patients gave a history of relaxing or straightening their hair. Six denied hair
      care practices sufficient to cause traction alopecia. In three patients, the hair
      care history was unknown. Occipital hair loss was a common clinical finding,
      mimicking alopecia areata. The presence of scarring was often subtle
      histologically. CONCLUSIONS: A group of patients with moderate to severe
      cicatricial alopecia of the scalp margin is described. The presence of scarring
      is difficult to diagnose both clinically and histologically. The lack of a
      history of severe traction or harsh styling practices in half the patients casts
      doubt on whether or not traction is the only pathogenic factor.

PMID- 18811692
TI  - Clinical significance of pretreatment serum amphiregulin and transforming growth
      factor-alpha, and an epidermal growth factor receptor somatic mutation in
      patients with advanced non-squamous, non-small cell lung cancer.
AB  - Circulating amphiregulin and transforming growth factor-alpha (TGF-alpha) have
      been found to be correlated with an unfavorable response to gefitinib based on
      the identification of patients with a higher probability of resistance to the
      drug. However, the association between an epidermal growth factor receptor (EGFR)
      somatic mutation and the overexpression of its ligands has not been determined.
      To verify the clinical significance of the two serum markers and EGFR mutation
      status, we determined serum amphiregulin and TGF-alpha levels by enzyme-linked
      immunosorbent assay in 93 patients with advanced non-squamous, non-small cell
      lung cancer and EGFR somatic mutation status using the peptic nucleic acid-locked
      nucleic acid clamp method in 46 cases. The relationship between each independent
      clinicopathological variable and the response to gefitinib therapy was examined.
      We also evaluated the risk factors associated with prognosis. Fourteen (41.0%) of
      34 progressive disease cases were positive for amphiregulin (P = 0.007). Eleven
      (32.4%) of 34 progressive disease cases were positive for TGF-alpha (P = 0.005).
      The median survival time of patients with the EGFR somatic mutation was
      significantly longer (P = 0.01). The same was true of amphiregulin- (P = 0.046)
      and TGF-alpha-negative patients (P < 0.01). In multivariate analysis, serum TGF
      alpha positivity (hazard ratio, 2.558; P = 0.005) and the wild type EGFR gene
      (hazard ratio, 1.894; P = 0.003) were significant independent prognostic factors.
      Our study demonstrates that the status of the serum EGFR ligand, in addition to
      EGFR activating mutation, is a predictive factor for response to gefitinib
      therapy.

PMID- 18811693
TI  - Increased shedding of soluble fragments of P-cadherin in nipple aspirate fluids
      from women with breast cancer.
AB  - Breast cancer, a worldwide disease with increasing incidence, develops from
      ductal/lobular epithelium. Nipple aspirate fluid (NAF), secreted from the breast
      ducts and lobules, can be analyzed to assess breast metabolic activity. P
      cadherin is frequently over-expressed in high-grade invasive breast carcinomas
      and has been reported to be an enhancer of migration and invasion of breast
      cancer cells, being correlated with tumor aggressiveness. The present study
      analyzed the soluble fragment of P-cadherin in milk, NAF and matched plasma
      samples of healthy subjects and in women with precancer conditions and breast
      cancer. Soluble P-cadherin was detected in all plasma and milk samples, and in
      about 31.3% of NAF samples. The lowest levels of soluble P-cadherin were found in
      plasma, with no significant difference among NoCancer, PreCancer and Cancer
      patients. The highest concentration of soluble P-cadherin was detected in milk
      collected during the first trimester of lactation, significantly with respect to
      all NAF samples. There were significantly higher levels of soluble P-cadherin in
      NAF from Cancer patients than those in women with NoCancer and PreCancer (P <
      0.0001). Although no significant difference was found between in situ and
      invasive breast cancer, soluble P-cadherin levels were found at high
      concentrations in c-erbB-2-positive tumors, showing a positive correlation with
      disease stage grouping and tumor grade, and an inverse relationship with
      estrogen/progesterone receptor status. High levels of the soluble fragment of P
      cadherin in Cancer NAF suggest its possible release via proteolytic processing,
      favoring cancer cell detachment from breast duct, and suggesting that measuring
      soluble P-cadherin in NAF may improve the identification of women with increased
      breast cancer risk.

PMID- 18811694
TI  - Longitudinal analysis of immune function in the first 3 years of life in
      thymectomized neonates during cardiac surgery.
AB  - The purpose of this study is to evaluate the effects of neonatal thymectomy in
      the functional capacity of the immune system. We selected a group of 23 subjects,
      who had undergone thymectomy in their first 30 days of life, during an
      intervention for congenital heart disease. Several parameters of the immune
      system were evaluated during their first 3 years of life. Lymphocyte populations
      and subpopulations (including naive, memory and effector subpopulations), T cell
      receptor (TCR) Vbeta repertoire, response of T cells following in vitro
      stimulation by mitogen, quantification of immunoglobulins, TCR excision circles
      (TRECS) and interleukin (IL)-7 were measured. We found that neonatal thymectomy
      produces long-term diminution in total lymphocyte counts, especially in naive
      CD4+ and CD8+ T cells. Additionally, TRECS were decreased, and plasma IL-7 levels
      increased. A statistically significant negative correlation was found between
      absolute CD4+ T cells and IL-7 (r = -0.470, P = 0.02). The patients did not
      suffer more infectious events than healthy control children, but thymectomy in
      neonates resulted in a significant decrease in T lymphocyte levels and TRECS,
      consistent with cessation of thymopoiesis. This could produce a compromise in
      immune function later in life, especially if the patients suffer T cell depletion
      and need a reconstitution of immune function.

PMID- 18811695
TI  - Analysis of the interindividual conservation of T cell receptor alpha- and beta
      chain variable regions gene in the peripheral blood of patients with systemic
      lupus erythematosus.
AB  - The aim of this study was to find conserved motifs in specific T cell receptor
      (TCR) alpha- and beta-chains, and to analyse the association between
      complementarity determining region 3 (CDR3) spectratype and systemic lupus
      erythematosus (SLE) activity. TCR alpha-and beta-chain CDR3 spectratypes were
      analysed in 20 SLE patients. The CDR3 spectratypes of three patients were
      monitored over time, and the CDR3 regions of clonally expanded T cells were
      sequenced. CDR3 spectratype analysis showed prominent usage of TCR AV8, AV14,
      AV23, AV30, AV31, BV2, BV8, BV11, BV14, BV16, BV19 and BV24 families in SLE
      patients. The CDR3 spectratype showed dynamic change correlating with SLE
      activity. The sequence of the CDR3 region in clonally expanded T cells suggested
      a conserved GGX amino acid motif in both alpha- and beta-chains. The Ja34 and
      Jb2s1 region genes were found in high frequency. Both TCR Valpha and Vbeta gene
      usage is highly restricted in SLE, suggesting that the TCRs recognize a limited
      number of antigenic epitopes. The conserved motifs and limited use of joining
      region genes may indicate the recognition of similar antigenic epitopes in
      multiple individuals.

PMID- 18811696
TI  - Role of the transgenic human thyrotropin receptor A-subunit in thyroiditis
      induced by A-subunit immunization and regulatory T cell depletion.
AB  - Transgenic BALB/c mice that express intrathyroidal human thyroid stimulating
      hormone receptor (TSHR) A-subunit, unlike wild-type (WT) littermates, develop
      thyroid lymphocytic infiltration and spreading to other thyroid autoantigens
      after T regulatory cell (T(reg)) depletion and immunization with human
      thyrotropin receptor (hTSHR) adenovirus. To determine if this process involves
      intramolecular epitope spreading, we studied antibody and T cell recognition of
      TSHR ectodomain peptides (A-Z). In transgenic and WT mice, regardless of T(reg)
      depletion, TSHR antibodies bound predominantly to N-terminal peptide A and much
      less to a few downstream peptides. After T(reg) depletion, splenocytes from WT
      mice responded to peptides C, D and J (all in the A-subunit), but transgenic
      splenocytes recognized only peptide D. Because CD4(+) T cells are critical for
      thyroid lymphocytic infiltration, amino acid sequences of these peptides were
      examined for in silico binding to BALB/c major histocompatibility complex class
      II (IA-d). High affinity subsequences (inhibitory concentration of 50% < 50 nm)
      are present in peptides C and D (not J) of the hTSHR and mouse TSHR equivalents.
      These data probably explain why transgenic splenocytes do not recognize peptide
      J. Mouse TSHR mRNA levels are comparable in transgenic and WT thyroids, but only
      transgenics have human A-subunit mRNA. Transgenic mice can present mouse TSHR and
      human A-subunit-derived peptides. However, WT mice can present only mouse TSHR,
      and two to four amino acid species differences may preclude recognition by CD4+ T
      cells activated by hTSHR-adenovirus. Overall, thyroid lymphocytic infiltration in
      the transgenic mice is unrelated to epitopic spreading but involves human A
      subunit peptides for recognition by T cells activated using the hTSHR.

PMID- 18811697
TI  - Identification of a previously unrecognized microdeletion syndrome of
      16q11.2q12.2.
AB  - We report the identification of microdeletions of 16q11.2q12.2 by microarray
      based comparative genomic hybridization (aCGH) in two individuals. The clinical
      features of these two individuals include hypotonia, gastroesophageal reflux, ear
      anomalies, and toe deformities. Other features include developmental delay,
      mental retardation, hypothyroidism, and seizures. The identification of common
      clinical features in these two individuals and those of one other report suggests
      microdeletion of 16q12.1q12.2 is a rare, emerging syndrome. These results
      illustrate that aCGH is particularly suited to identify rare chromosome
      abnormalities in patients with apparently non-syndromic idiopathic mental
      retardation and birth defects.

PMID- 18811698
TI  - A novel genetic locus for benign familial infantile seizures maps to chromosome
      1p36.12-p35.1.

PMID- 18811700
TI  - Unravelling the cerebral palsy upper limb.

PMID- 18811701
TI  - Comparison of the Melbourne Assessment of Unilateral Upper Limb Function and the
      Quality of Upper Extremity Skills Test in hemiplegic CP.
AB  - This study investigated interrater reliability and measurement error of the
      Melbourne Assessment of Unilateral Upper Limb Function (Melbourne Assessment) and
      the Quality of Upper Extremity Skills Test (QUEST), and assessed the relationship
      between both scales in 21 children (15 females, six males; mean age 6y 4mo [SD 1y
      3mo], range 5-8y) with hemiplegic CP. Two raters scored the videotapes of the
      assessments independently in a randomized order. According to the House
      Classification, three participants were classified as level 1, one participant as
      level 3, eight as level 4, three as level 5, one participant as level 6, and five
      as level 7. The Melbourne Assessment and the QUEST showed high interrater
      reliability (intraclass correlation 0.97 for Melbourne Assessment; 0.96 for QUEST
      total score; 0.96 for QUEST hemiplegic side). The standard error of measurement
      and the smallest detectable difference was 3.2% and 8.9% for the Melbourne
      Assessment and 5.0% and 13.8% for the QUEST score on the hemiplegic side.
      Correlation analysis indicated that different dimensions of upper limb function
      are addressed in both scales.

PMID- 18811702
TI  - The significance of specific diagnosis in the treatment of epilepsies.

PMID- 18811703
TI  - Do patients with congenital hemiparesis and ipsilateral corticospinal projections
      respond differently to constraint-induced movement therapy?
AB  - This study investigates whether the type of corticospinal reorganization
      (identified by transcranial magnetic stimulation) influences the efficacy of
      constraint-induced movement therapy (CIMT). Nine patients (five males, four
      females; mean age 16y [SD 6y 5mo], range 11-30y) controlling their paretic hand
      via ipsilateral corticospinal projections from the contralesional hemisphere and
      seven patients (three males, four females; mean age 17y [SD 7y], range 10-30y)
      with preserved crossed corticospinal projections from the affected hemisphere to
      the paretic hand underwent 12 consecutive days of CIMT. A Wolf motor function
      test applied before and after CIMT revealed a significant improvement in the
      quality of upper extremity movements in both groups. Only in patients with
      preserved crossed projections, however, was this amelioration accompanied by a
      significant gain in speed, whereas patients with ipsilateral projections tended
      to show speed reduction. These data, although preliminary, suggest that patients
      with congenital hemiparesis and ipsilateral corticospinal projections respond
      differently to CIMT.

PMID- 18811704
TI  - Motor coordination difficulties and physical fitness of extremely-low-birthweight
      children.
AB  - Motor coordination difficulties and poor fitness exist in the extremely low
      birthweight (ELBW) population. This study investigated the relative impact of
      motor coordination on the fitness of ELBW children aged 11 to 13 years. One
      hundred and nine children were recruited to the study: 54 ELBW participants (mean
      age at assessment 12y 6mo; 31 male, 23 female; mean birthweight 769g, SD 148g;
      mean gestational age 26.6 weeks, SD 2.1 weeks) and 55 comparison children (mean
      age at assessment 12y 5mo; 28 males, 27 females; at least 37 weeks' gestation).
      All children completed the Movement Assessment Battery for Children (MABC),
      functional tests of postural stability and strength, growth measures, and tests
      of respiratory function. Maximal oxygen uptake (VO(2)max) was calculated from a
      20m shuttle run test as a measure of fitness. The ELBW group had greater problems
      with postural stability (p=0.001) and motor coordination (p=0.001), with 70%
      rated as having a definite motor problem on the MABC brackets (those who scored
      less than the 5(th) centile on the MABC). The ELBW was also less fit than the
      comparison group (p=0.001), with 45% below the 10th centile for VO(2)max. There
      were differences between the groups for growth, strength, and particularly
      respiratory function. However, respiratory function did not significantly
      correlate with VO(2)max in the ELBW group. Motor coordination was the most
      powerful predictor of VO(2)max in both the ELBW (p=0.001) and the comparison
      groups (p=0.001).

PMID- 18811705
TI  - 'Succinic semialdehyde dehydrogenase deficiency: phenotype evolution in an
      adolescent patient at 20-year follow-up'.

PMID- 18811706
TI  - Waiting for child developmental and rehabilitation services: an overview of
      issues and needs.
AB  - Concern about the length of time that children, young people, and families may
      have to wait to access assessment, diagnostic, interventional, therapeutic, and
      supportive child developmental and rehabilitation (CDR) services is widespread,
      but adequate data collection and research on this issue remain limited. We review
      key concepts and issues relevant to waiting for CDR services from the published
      literature, a national workshop devoted to this topic, and international
      experience. We conclude that gaps in data, evidence, and consensus challenge our
      ability to address the issue of waiting for CDR services in a systematic way. A
      program of research coupled with actions based on consensus-building is required.
      Research priorities include acquiring evidence of the appropriateness and
      effectiveness of different models of intervention and rehabilitation services,
      and documenting the experience and expectations of waiting families. Consensus
      building processes are critical to identify, categorize, and prioritize
      'sentinel' components of CDR service pathways: (1) to reduce the inherent
      complexity of the field; (2) to create benchmarks for waiting for these
      respective services; and (3) to develop definitions for wait-time subcomponents
      in CDR services. Collection of accurate and replicable data on wait times for CDR
      services can be used to document baseline realities, to monitor and improve
      system performance, and to conduct comparative and analytic research in the field
      of CDR services.

PMID- 18811707
TI  - 'Absence of T378N mutation of ATP1A2 gene in five patients with alternating
      hemiplegia of childhood'.

PMID- 18811708
TI  - Recognizing problems in movement coordination.

PMID- 18811709
TI  - Influence of behaviour and risk factors on motor performance in preterm infants
      at age 2 to 3 years.
AB  - The aim of this cross-sectional study was to determine the influence of test
      taking behaviour and risk factors for delayed motor performance in 437 preterm
      infants (244 males, 193 females; < or = 32 weeks of gestation) at the corrected
      age of 2 to 3 years (mean 29mo [SD 3.3]). Other mean (SD) sample demographics
      were: postmenstrual age 29(+5) weeks (1(+5)), range 25(+0)-32(+0); birthweight
      1213.7g (331.7), range 468-2350; and days in the neonatal intensive care unit
      21.1 (21.3), range 1-165. Children (n=23) with a severe disability were excluded.
      We assessed motor performance and behaviour during testing with the Motor Scale
      and the Behaviour Rating Scale (BRS) of the Bayley Scales of Infant Development,
      2nd edition (BSID-II). Risk factors were tested against delayed motor performance
      as the dependent variable in binary logistic regression analysis. Median score on
      the Motor Scale in terms of the BSID-II Psychomotor Developmental Index (PDI) was
      86. 'Delayed' motor performance was observed in 46.5% of the children tested, and
      behaviour was 'not-optimal' in 31.4%. The Motor Scale and BRS scores were
      significantly correlated (r(s)=0.62, p<0.01). Risk factors for delayed motor
      performance were: neonatal convulsions (odds ratio [OR] 4.5; 95% confidence
      interval [CI] 1.6-12.9), low maternal educational level (OR 3.3; 95% CI 1.7-6.5),
      male sex (OR 2.8; 95% CI 1.8-4.3), and chronic lung disease (OR 2.1; 95% CI 1.1-
      4.1). We conclude that preterm infants are at high risk of delayed motor
      performance and non-optimal test-taking behaviour.

PMID- 18811710
TI  - Tactile sensory abilities in cerebral palsy: deficits in roughness and object
      discrimination.
AB  - Motor deficits in cerebral palsy (CP) have been well documented; however,
      associated sensory impairment in CP remains poorly understood. We examined
      tactile object recognition in the hands using geometric shapes, common objects,
      and capital letters. Discrimination of tactile roughness was tested using paired
      horizontal gratings of varied groove widths passively translated across the index
      finger. We tested 17 individuals with hemiplegia (mean 13y 9mo [SD 5y 2mo]; 6
      males, 11 females), 21 with diplegia (mean 14y 10mo [SD 7y]; 10 males, 11
      females), and 21 without disabilities (mean 14y 10mo [SD 5y 1mo]; 11 males, 10
      females). All participants with CP fell within level I or II of the Gross Motor
      Function Classification System and level I or II of the Manual Abilities
      Classification System. Individuals with CP were significantly less accurate
      compared with those without disabilities on all tactile object-recognition tasks
      using their non-dominant hand. Both groups of patients also had significantly
      higher thresholds for groove-width differences with both hands compared with
      those without disabilities. Within the group with diplegia, only roughness
      discrimination differed between hands, whereas within the group with hemiplegia,
      significant between-limb differences were present for all tasks. Despite mild
      motor deficits compared with the entire population of individuals with CP, this
      sample demonstrated ubiquitous tactile deficits.

PMID- 18811711
TI  - Bone mineral density in children with myelomeningocele.
AB  - The aim of the present study was to document bone mineral density (BMD) in
      children with myelomeningocele and to identify variables that contribute to
      reduced BMD. The study included 24 children with myelomeningocele (nine males, 15
      females; age range 4-18y), who had varied levels of neurological impairment
      (thoracic/high-lumbar, n=6; mid-lumbar, n=9; sacral, n=9) and ambulatory status
      (non-ambulators, n=12; part-time ambulators n=2; full-time ambulators, n=10). BMD
      measurements of the femoral neck and whole body using dual energy X-ray
      absorptiometry assessments of dietary calcium intake, and serum markers of bone
      metabolism were obtained. BMD is presented as standardized scores (z-scores)
      which are age- and sex-matched to normally developing children. The mean femoral
      neck z-score was -2.41. Femoral-neck z-scores differed significantly according to
      ambulatory status, with lower z-scores in children who were wheelchair-dependent
      (p=0.03). The mean z-score at the femoral neck demonstrated a trend toward lower
      z-scores in children with higher levels of lesions. Almost all children met their
      recommended daily intake of calcium. Markers of bone metabolism were normal in
      all patients. This study demonstrates that reduced BMD is a major complication in
      children with myelomeningocele. There is a significant relationship with low BMD
      in children who are wheelchair-dependent, a trend in those with higher
      neurological levels, and no relationship between fractures and reduced BMD.

PMID- 18811712
TI  - Quantification of upper extremity function and range of motion in children with
      cerebral palsy.
AB  - This study evaluated the hypothesis that upper extremity function and range of
      motion can be quantified reliably in children with cerebral palsy (CP) in a busy
      clinical setting. The specific aim was to determine the inter- and intrarater
      reliability of a modified House Functional Classification (MHC) system to
      evaluate upper extremity function and a standardized instrument to document upper
      extremity range of motion (Upper Extremity Rating Scale [UERS]). Sixty-five
      children with CP (43 males, 22 females, mean age 9y 2mo, SD 4y 1mo) with
      spasticity involving the upper extremity (quadriplegia n=22; hemiplegia n=36;
      diplegia n=7; Gross Motor Functional Classification System Levels I n=41, II n=6,
      III n=3, IV n=5, V n=10) were evaluated independently by occupational therapists
      and orthopedic surgeons using both instruments at several visits. Inter- and
      intrarater reliability were determined for both instruments by calculating
      measures of agreement (weighted kappa values and intraclass correlation
      coefficients [ICCs]). Interrater agreement (ICC=0.94) and intrarater agreement
      (ICC=0.96) on the MHC were good to excellent. Similarly, inter-rater agreement
      (kappa 0.66-0.81) and intrarater agreement (kappa 0.64-0.88) on the UERS was
      either good or excellent. The MHC and the UERS provide standardized, reliable,
      reproducible, and efficient instruments that can be used by occupational
      therapists and orthopedic surgeons to evaluate the upper extremities of children
      with CP.

PMID- 18811713
TI  - Description of children identified by physicians as having developmental
      coordination disorder.
AB  - The aim of this study was to describe in detail a large group of children aged 4
      to 12 years who were diagnosed with developmental coordination disorder (DCD) by
      physicians following a rigorous multidisciplinary procedure. As part of a
      community-based DCD knowledge translation program, physicians received
      specialized training and were invited to identify children with probable DCD who
      were referred for further investigation to help confirm the diagnosis. Of 116
      children (87 males, 29 females; age range 4y 1mo - 12y 11mo, mean age 8y)
      identified as having probable DCD by physician participants, 88 (76%) were
      subsequently diagnosed with DCD and 77.3% of these demonstrated a high degree of
      motor impairment. All children who were diagnosed experienced difficulties in
      self-care and/or academic or leisure activities. The male:female ratio was 3:1
      and the incidence of preterm births among this sample was 12.5%. We conclude
      that, given the expense involved with ruling out differential diagnoses, it can
      be difficult to adhere rigorously to diagnostic criteria for DCD in clinical
      practice and research. This description of a group of children actually diagnosed
      with DCD helps to clarify the characteristics of these children as well as issues
      related to the refinement of diagnostic criteria.

PMID- 18811714
TI  - A systematic review of the effectiveness of aerobic exercise interventions for
      children with cerebral palsy: an AACPDM evidence report.
AB  - The aim of this review was to assess the evidence regarding the effectiveness of
      aerobic training interventions for children with cerebral palsy (CP). The target
      population included children with CP of any severity, aged 2 to 17 years. The
      following databases were searched for English language studies from 1960 to 2006:
      MEDLINE, EMBASE, CINAHL, Pascal, Cochrane Library, CSA Neuroscience Abstracts,
      The Physiotherapy Evidence Database (PEDro), and Sport Discus. Search terms
      included 'cerebral palsy', 'athetoid', 'ataxic', 'spastic diplegia',
      'hemiplegia', 'quadriplegia', 'aerobic', 'exercise', 'training', 'physical
      activity', 'aquatic/water/pool therapy', and 'continuous exercise'. The American
      Academy for Cerebral Palsy and Developmental Medicine systematic review
      guidelines were used to format the review. One thousand, four hundred and eighty
      nine articles were identified and examined for the stated inclusion and exclusion
      criteria. Thirteen articles met the criteria for inclusion. The evidence suggests
      that aerobic exercise with children with CP can improve physiological outcomes,
      but the influence of these changes on outcomes representing activity and
      participation are unknown. Future research needs improved methodological rigour
      in order to determine a specific set of exercise guidelines and safety
      considerations.

PMID- 18811715
TI  - Evaluation of injectable calcium hydroxylapatite for the treatment of facial
      lipoatrophy associated with human immunodeficiency virus.
AB  - OBJECTIVE: To evaluate the safety and effectiveness of soft tissue augmentation
      with calcium hydroxylapatite (CaHA) microspheres in an aqueous gel in patients
      with facial lipoatrophy (FLA) secondary to human immunodeficiency virus (HIV)
      disease. METHODS: This 12-month open-label, prospective study enrolled 30
      subjects (29 men and 1 woman) with HIV-associated FLA. After the initial
      treatment phase (up to 2 injections, 30 days apart), patients were followed up at
      3, 6, and 12 months. Patients were offered touch-up injections at 6 and 12
      months. Measurements included confirmed changes in the Global Aesthetic
      Improvement Scale and in cheek thickness. RESULTS: Average initial treatment
      volume was 9.5 mL per patient (both sides); total volumes per patient after 12
      months averaged 16.1 mL. At all time points, all patients were rated as improved
      or better and responded affirmatively to satisfaction questions. Cheek thickness
      measurements increased substantially over baseline (p<.001). Most commonly
      reported adverse events were edema (93%), ecchymosis (83%), and erythema (77%).
      CONCLUSIONS: CaHA is an appropriate and well-tolerated treatment for patients
      with HIV-associated FLA. With an excellent safety profile, CaHA provides
      immediate correction of FLA and appears to provide lasting improvement in
      appearance.

PMID- 18811716
TI  - A novel 2-hour method for rapid preparation of permanent paraffin sections when
      treating melanoma in situ with mohs micrographic surgery.
AB  - BACKGROUND: Distinguishing sun-induced melanocyte atypia from residual melanoma
      in situ (MIS) can be challenging, particularly when working with frozen sections.
      Immunostains such as melanoma-associated antigen recognized by T cells (MART-1)
      can assist, but paraffin sections provide an optimal means of analyzing
      melanocyte morphology. OBJECTIVE: To verify the effectiveness of a 2-hour
      paraffin processing technique that uses microwave technology in the preparation
      of MIS sections. METHODS: Twelve MIS debulk specimens were divided into 4 pieces
      with each piece processed 1 of 4 ways: our 2-hour paraffin technique with
      hematoxylin and eosin (H&E), conventional 24-hour paraffin processing with H&E,
      frozen sections with H&E, and frozen sections with MART-1 immunostaining. A Mohs
      surgeon and a dermatopathologist compared all specimens in a blinded fashion
      using a 3-point ranking scale to assess ease of visualizing normal melanocytes,
      ease of visualizing abnormal melanocytes, and overall ability to adequately
      visualize epidermal and dermal structures. RESULTS: A nonparametric signed rank
      test indicated no significant differences between our microwave technique and
      conventional paraffin processing in all 3 criteria (p=.29, .63, .75,
      respectively). Our microwave technique was significantly better than frozen H&E
      sections for all 3 criteria (p=.046, .004, .005, respectively). CONCLUSION: This
      rapid microwave tissue processing technique is comparable with conventional
      paraffin section processing.

PMID- 18811717
TI  - Safety of phenol vapor inhalation during performance of chemical matrixectomy to
      treat ingrown toenails.
AB  - BACKGROUND: Phenol is commonly used in chemical matrixectomies to treat ingrown
      toenails. Although many studies have documented the safety of phenol matrixectomy
      for the patient, few studies have investigated the procedure's safety for the
      physician and auxiliary health care personnel. OBJECTIVE: This study was
      undertaken to evaluate the safety of phenol vapor inhalation for health care
      personnel during performance of chemical matrixectomy. METHODS: The environmental
      concentrations of phenol in the respiration zones of the physician and an
      assistant were measured during an in-office surgical procedure consisting of two
      partial chemical matrixectomies using a 95% phenol solution. The samples were
      analyzed using gas chromatography with a flame ionization detector. RESULTS: The
      phenol concentration measured in the physician's respiration zone was close to
      Spain's established environmental limit of daily exposure, with an index of
      exposure of 60%. The concentration measured in the assistant's respiration zone
      was well below the environmental limit of daily exposure, with an index of
      exposure of only 10%. CONCLUSION: The performance of chemical matrixectomies is
      safe for health care personnel when they are exposed to the vapor of phenol
      solutions of up to 95% concentration for up to 21 minutes. The degree of safety
      would be greater with lower phenol concentrations and shorter exposure times.

PMID- 18811718
TI  - Pilot investigation of the correlation between histological and clinical effects
      of infrared fractional resurfacing lasers.
AB  - METHODS: Yucatan Black pig skin was treated with a 1,540-nm erbium (Er):glass
      laser (Lux1540, 15 and 30 mJ) and two 1,550-nm Er-doped fiber lasers (Fraxel
      SR750 and SR1500, 8, 10, and 12 mJ). Histologic sections were examined to
      determine the depth of damage and to correlate subjects' clinical response.
      Concurrently, six subjects with photodamaged skin received three split-face and
      ipsilateral dorsal hand treatments with the 1,540-nm Er:glass laser on one side
      and one of the 1,550-nm Er-doped lasers (Fraxel SR750) on the other. RESULTS: The
      1,550-nm Er-doped lasers, using lower fluences and higher densities, produced
      shallower micro-columns than the 1,540-nm Er:glass device at higher fluences and
      lower densities (mean depths 250-275 microm vs 425-525 microm, respectively).
      Blinded assessors found greater overall improvement in pigmentation with the
      1,550-nm Er-doped laser and better overall improvement in texture with the 1,540
      nm Er:glass laser. CONCLUSIONS: Greater densities of shallower damage columns at
      lower energies may better improve pigmentation, whereas deeper injuries, using
      higher energies and moderate densities, may better improve texture. This pilot
      study did not compare similar fluences and histologic damage between the two
      systems, and newer available systems allow for greater depth of penetration.

PMID- 18811719
TI  - A nuc-deficient methicillin-resistant Staphylococcus aureus strain.

PMID- 18811720
TI  - Structure of the glycerol phosphate-containing O-specific polysaccharide and
      serological studies on the lipopolysaccharides of Citrobacter werkmanii PCM 1548
      and PCM 1549 (serogroup O14).
AB  - The O-specific polysaccharide was obtained by mild acid hydrolysis of the
      lipopolysaccharide of Citrobacter werkmanii PCM 1548 and PCM 1549 (serogroup O14)
      and found to contain D-glucose, D-glucosamine and glycerol-1-phosphate in molar
      ratios 2 : 2 : 1. Based on methylation analysis and 1H and 13C nuclear magnetic
      resonance spectroscopy data, it was established that the O-specific
      polysaccharides from both strains have the identical branched tetrasaccharide
      repeating unit with 3,6-disubstituted GlcNAc, followed by 2,4-disubstituted Glc
      residues carrying at the branching points lateral residues of Glc and GlcNAc at
      positions 6 and 2, respectively. Glycerol-1-phosphate is linked to position 6 of
      the chain Glc. All sugars have a beta configuration, except for the side-chain
      Glc, which is alpha. Serological studies revealed a close relatedness of the
      lipopolysaccharides of C. werkmanii PCM 1548 and PCM 1549, both belonging to
      serogroup O14. In immunoblotting, anti-C. werkmanii PCM 1548 serum showed no
      cross-reactivity with the O-polysaccharide bands of the lipopolysaccharides of
      Citrobacter youngae PCM 1550 (serogroup O16) and Hafnia alvei PCM 1207, also
      containing a lateral glycerol phosphate residue.

PMID- 18811722
TI  - MIBG scans for phaeochromocytoma: time to abandon the technique?

PMID- 18811723
TI  - [18F]FDG PET/CT in pancreatic neuroendocrine tumours associated with von Hippel
      Lindau Syndrome.

PMID- 18811724
TI  - Mutations of maturity-onset diabetes of the young (MODY) genes in Thais with
      early-onset type 2 diabetes mellitus.
AB  - OBJECTIVE: Six known genes responsible for maturity-onset diabetes of the young
      (MODY) were analysed to evaluate the prevalence of their mutations in Thai
      patients with MODY and early-onset type 2 diabetes. PATIENTS AND METHODS: Fifty
      one unrelated probands with early-onset type 2 diabetes, 21 of them fitted into
      classic MODY criteria, were analysed for nucleotide variations in promoters,
      exons, and exon-intron boundaries of six known MODY genes, including HNF-4alpha,
      GCK, HNF-1alpha, IPF-1, HNF-1beta, and NeuroD1/beta2, by the polymerase chain
      reaction-single strand conformation polymorphism (PCR-SSCP) method followed by
      direct DNA sequencing. Missense mutations or mutations located in regulatory
      region, which were absent in 130 chromosomes of non-diabetic controls, were
      classified as potentially pathogenic mutations. RESULTS: We found that mutations
      of the six known MODY genes account for a small proportion of classic MODY (19%)
      and early-onset type 2 diabetes (10%) in Thais. Five of these mutations are novel
      including GCK R327H, HNF-1alpha P475L, HNF-1alphaG554fsX556, NeuroD1-1972 G > A
      and NeuroD1 A322N. Mutations of IPF-1 and HNF-1beta were not identified in the
      studied probands. CONCLUSIONS: Mutations of the six known MODY genes may not be a
      major cause of MODY and early-onset type 2 diabetes in Thais. Therefore,
      unidentified genes await discovery in a majority of Thai patients with MODY and
      early-onset type 2 diabetes.

PMID- 18811725
TI  - 46,XY disorders of sex development (DSD).
AB  - The term disorders of sex development (DSD) includes congenital conditions in
      which development of chromosomal, gonadal or anatomical sex is atypical.
      Mutations in genes present in X, Y or autosomal chromosomes can cause
      abnormalities of testis determination or disorders of sex differentiation leading
      to 46,XY DSD. Detailed clinical phenotypes allow the identification of new
      factors that can alter the expression or function of mutated proteins helping to
      understand new undisclosed biochemical pathways. In this review we present an
      update on 46,XY DSD aetiology, diagnosis and treatment based on extensive review
      of the literature and our three decades of experience with these patients.

PMID- 18811726
TI  - Inducible protein degradation in Bacillus subtilis using heterologous peptide
      tags and adaptor proteins to target substrates to the protease ClpXP.
AB  - The ability to manipulate protein levels is useful for dissecting regulatory
      pathways, elucidating gene function and constructing synthetic biological
      circuits. We engineered an inducible protein degradation system for use in
      Bacillus subtilis based on Escherichia coli and Caulobacter crescentusssrA tags
      and SspB adaptors that deliver proteins to ClpXP for proteolysis. In this system,
      modified ssrA degradation tags are fused onto the 3' end of the genes of
      interest. Unlike wild-type ssrA, these modified tags require the adaptor protein
      SspB to target tagged proteins for proteolysis. In the absence of SspB, the
      tagged proteins accumulate to near physiological levels. By inducing SspB
      expression from a regulated promoter, the tagged substrates are rapidly delivered
      to the B. subtilis ClpXP protease for degradation. We used this system to degrade
      the reporter GFP and several native B. subtilis proteins, including, the
      transcription factor ComA, two sporulation kinases (KinA, KinB) and the
      sporulation and chromosome partitioning protein Spo0J. We also used modified E.
      coli and C. crescentus ssrA tags to independently control the degradation of two
      different proteins in the same cell. These tools will be useful for studying
      biological processes in B. subtilis and can potentially be modified for use in
      other bacteria.

PMID- 18811727
TI  - Nitric oxide-induced bacteriostasis and modification of iron-sulphur proteins in
      Escherichia coli.
AB  - The nitric oxide (NO) cytotoxicity has been well documented in bacteria and
      mammalian cells. However, the underlying mechanism is still not fully understood.
      Here we report that transient NO exposure effectively inhibits cell growth of
      Escherichia coli in minimal medium under anaerobic growth conditions and that
      cell growth is restored when the NO-exposed cells are either supplemented with
      the branched-chain amino acids (BCAA) anaerobically or returned to aerobic growth
      conditions. The enzyme activity measurements show that dihydroxyacid dehydratase
      (IlvD), an iron-sulphur enzyme essential for the BCAA biosynthesis, is completely
      inactivated in cells by NO with the concomitant formation of the IlvD-bound
      dinitrosyl iron complex (DNIC). Fractionation of the cell extracts prepared from
      the NO-exposed cells reveals that a large number of different protein-bound DNICs
      are formed by NO. While the IlvD-bound DNIC and other protein-bound DNICs are
      stable in cells under anaerobic growth conditions, they are efficiently repaired
      under aerobic growth conditions even without new protein synthesis. Additional
      studies indicate that L-cysteine may have an important role in repairing the NO
      modified iron-sulphur proteins in aerobically growing E. coli cells. The results
      suggest that cellular deficiency to repair the NO-modified iron-sulphur proteins
      may directly contribute to the NO-induced bacteriostasis under anaerobic
      conditions.

PMID- 18811728
TI  - The rate of protein secretion dictates the temporal dynamics of flagellar gene
      expression.
AB  - Flagellar gene expression is temporally regulated in response to the assembly
      state of the growing flagellum. The key mechanism for enforcing this temporal
      hierarchy in Salmonella enterica serovar Typhimurium is the sigma(28)-FlgM
      checkpoint, which couples the expression of the late flagellar (P(class3)) genes
      to the completion of the hook-basal body. This checkpoint is triggered when FlgM
      is secreted from the cell. In addition to the sigma(28)-FlgM checkpoint, a number
      of other regulatory mechanisms respond to the secretion of late proteins. In this
      work, we examined how middle (P(class2)) and late (P(class3)) gene expression is
      affected by late protein secretion. Dynamic analysis of flagellar gene expression
      identified a novel mechanism where induction of P(class2) activity is delayed
      either when late protein secretion is abolished or when late protein secretion is
      increased. Using a number of different approaches, we were able to show that this
      mechanism did not involve any known flagellar regulator. Furthermore, the changes
      in P(class2) activity were not correlated with the associated changes in
      P(class3) activity, which was found to be proportional to late protein secretion
      rates. Our data indicate that both P(class2) and P(class3) promoters are
      continuously regulated in response to assembly and late protein secretion rates.
      These results suggest that flagellar regulation is more complex than previously
      thought.

PMID- 18811729
TI  - A Dot/Icm-translocated ankyrin protein of Legionella pneumophila is required for
      intracellular proliferation within human macrophages and protozoa.
AB  - The Dot/Icm type IV secretion system of Legionella pneumophila translocates
      numerous bacterial effectors into the host cell and is essential for bacterial
      proliferation within macrophages and protozoa. We have recently shown that L.
      pneumophila strain AA100/130b harbours 11 genes encoding eukaryotic-like ankyrin
      (Ank) proteins, a family of proteins involved in various essential eukaryotic
      cellular processes. In contrast to most Dot/Icm-exported substrates, which have
      little or no detectable role in intracellular proliferation, a mutation in ankB
      results in a severe growth defect in intracellular replication within human
      monocyte-derived macrophages (hMDMs), U937 macrophages and Acanthamoeba
      polyphaga. Single cell analyses of coinfections of hMDMs have shown that the
      intracellular growth defect of the ankB mutant is totally rescued in cis within
      communal phagosomes harbouring the wild type strain. Interestingly, distinct from
      dot/icm structural mutants, the ankB mutant is also rescued in trans within cells
      harbouring the wild type strain in a different phagosome, indicating that AnkB is
      a trans-acting secreted effector. Using adenylate cyclase fusions to AnkB, we
      show that AnkB is translocated into the host cell via the Dot/Icm secretion
      system in an IcmSW-dependent manner and that the last three C-terminal amino acid
      residues are essential for translocation. Distinct from the dot/icm structural
      mutants, the ankB mutant-containing phagosomes exclude late endosomal and
      lysosomal markers and their phagosomes are remodelled by the rough endoplasmic
      reticulum. We show that at the postexponential phase of growth, the LetA/S and
      PmrA/B Two Component Systems confer a positive regulation on expression of the
      ankB gene, whereas RpoS, LetE and RelA suppress its expression. Our data show
      that the eukaryotic-like AnkB protein is a Dot/Icm-exported effector that plays a
      major role in intracellular replication of L. pneumophila within macrophages and
      protozoa, and its expression is temporally controlled by regulators of the
      postexponential phase of growth.

PMID- 18811730
TI  - Isoprene and nitric oxide reduce damages in leaves exposed to oxidative stress.
AB  - Isoprene and nitric oxide (NO) are two volatile molecules that are produced in
      leaves. Both compounds were suggested to have an important protective role
      against stresses. We tested, in two isoprene-emitting species, Populus nigra and
      Phragmites australis, whether: (1) NO emission outside leaves is measurable and
      is affected by oxidative stresses; and (2) isoprene and NO protect leaves against
      oxidative stresses, both singularly and in combination. The emission of NO was
      undetectable, and the compensation point was very low in control poplar leaves.
      Both emission and compensation point increased dramatically in stressed leaves.
      NO emission was inversely associated with stomatal conductance. More NO was
      emitted in leaves that were isoprene-inhibited, and more isoprene was emitted
      when NO was reduced by NO scavenger c-PTIO. Both isoprene and NO reduced
      oxidative damages. Isoprene-emitting leaves which were also fumigated with NO, or
      treated with NO donor, showed low damage to photosynthesis, a reduced
      accumulation of H(2)O(2) and a reduced membrane denaturation. We conclude that
      measurable amounts of NO are only produced and emitted by stressed leaves, that
      both isoprene and NO are effective antioxidant molecules and that an additional
      protection is achieved when both molecules are released.

PMID- 18811731
TI  - The role of ultraviolet radiation, photosensitizers, reactive oxygen species and
      ester groups in mechanisms of methane formation from pectin.
AB  - Ultraviolet (UV) radiation has recently been demonstrated to drive an aerobic
      production of methane (CH(4)) from plant tissues and pectins, as do agents that
      generate reactive oxygen species (ROS) in vivo independently of UV. As the major
      building-blocks of pectin do not absorb solar UV found at the earth's surface
      (i.e. >280 nm), we explored the hypothesis that UV radiation affects pectin
      indirectly via generation of ROS which themselves release CH(4) from pectin.
      Decreasing the UV absorbance of commercial pectin by ethanol washing diminished
      UV-dependent CH(4) production, and this was restored by the addition of the UV
      photosensitizer tryptophan. Certain ROS scavengers [mannitol, a hydroxyl radical
      ((*)OH) scavenger; 1,4-diazabicyclo[2.2.2] octane; and iodide] strongly inhibited
      UV-induced CH(4) production from dry pectin. Furthermore, pectin solutions
      emitted CH(4) in darkness upon the addition of (*)OH, but not superoxide or
      H(2)O(2). Model carbohydrates reacted similarly if they possessed -CH(3) groups
      [e.g. methyl esters or (more weakly) acetyl esters but not rhamnose]. We conclude
      that UV evokes CH(4) production from pectic methyl groups by interacting with UV
      photosensitizers to generate (*)OH. We suggest that diverse processes generating
      (*)OH could contribute to CH(4) emissions independently of UV irradiation, and
      that environmental stresses and constitutive physiological processes generating
      ROS require careful evaluation in studies of CH(4) formation from foliage.

PMID- 18811732
TI  - Root decisions.
AB  - Root systems have recognizable developmental plans when grown in solution or
      agar; however, these plans often must be modified to cope with the prevailing
      conditions in the soil environment such as the avoidance of obstacles and the
      exploitation of nutrient-rich patches or water zones. The modular structure of
      roots enables them to respond to their environment, and roots are very adaptive
      at modifying growth throughout the root system to concentrate their efforts in
      the areas that are the most profitable. Roots also form associations with
      microorganisms as a strategy to enhance resource capture. However, while the
      responses of roots in nutrient patches are well-recognized, overall 'rules of
      response' and variation in strategy among plant species that can be applied in a
      number of different environments are still lacking. Finally, there is increasing
      evidence that root-root interactions are much more sophisticated than previously
      thought, and the evidence for roots to identify self from non-self roots will be
      briefly discussed.

PMID- 18811733
TI  - Loss of cytosolic fructose-1,6-bisphosphatase limits photosynthetic sucrose
      synthesis and causes severe growth retardations in rice (Oryza sativa).
AB  - During photosynthesis, triose-phosphates (trioseP) exported from the chloroplast
      to the cytosol are converted to sucrose via cytosolic fructose-1,6-bisphosphatase
      (cFBPase). Expression analysis in rice suggests that OscFBP1 plays a major role
      in the cytosolic conversion of trioseP to sucrose in leaves during the day. The
      isolated OscFBP1 mutants exhibited markedly decreased photosynthetic rates and
      severe growth retardation with reduced chlorophyll content, which results in
      plant death. Analysis of primary carbon metabolites revealed both significantly
      reduced levels of sucrose, glucose, fructose and starch in leaves of these
      mutants, and a high accumulation of sucrose to starch in leaves of rice plants.
      In the oscfbp1 mutants, products of glycolysis and the TCA cycle were
      significantly increased. A partitioning experiment of (14)C-labelled
      photoassimilates revealed altered carbon distributions including a slight
      increase in the insoluble fraction representing transitory starch, a significant
      decrease in the neutral fraction corresponding to soluble sugars and a high
      accumulation of phosphorylated intermediates and carboxylic acid fractions in the
      oscfbp1 mutants. These results indicate that the impaired synthesis of sucrose in
      rice cannot be sufficiently compensated for by the transitory starch-mediated
      pathways that have been found to facilitate plant growth in the equivalent
      Arabidopsis mutants.

PMID- 18811734
TI  - Root of edaphically controlled Proteaceae turnover on the Agulhas Plain, South
      Africa: phosphate uptake regulation and growth.
AB  - The influence of phosphorus (P) availability on growth and P uptake was
      investigated in South African Proteaceae: (1) Protea compacta R.Br., endemic on
      severely nutrient-impoverished colluvial sands; (2) Protea obtusifolia Bueck ex
      Meissner; and (3) Leucadendron meridianum I. J. Williams, the latter both endemic
      on comparatively fertile limestone-derived soils. Plants were grown
      hydroponically in 1000 L tanks at 0.01, 0.1 or 1.0 microm P for 14 weeks. Biomass
      accumulation was influenced by P availability, doubling as [P] increased from 0.1
      to 1.0 microm. Total biomass was greatest for P. compacta, but L. meridianum and
      P. obtusifolia had two to four times greater relative biomass accumulation at 0.1
      and 1.0 microm [P]. Proteoid root clusters developed at both 0.01 and 0.1
      microm[P], but were suppressed at 1.0 microm [P]; this was a 10-fold lower [P]
      than previously reported to inhibit cluster root formation. Rates of net P uptake
      at 5 microm P decreased in response to increased P availability from 0.01 to 1.0
      microm P. Significant between-species differences in rates of P uptake and
      capacity to down-regulate P uptake were observed: P. compacta < P. obtusifolia <
      L. meridianum. The species responses are discussed in terms of adaptation to
      mosaics in soil P availability and the high beta diversity in the natural
      habitat.

PMID- 18811735
TI  - Carbon monoxide enhances salt tolerance by nitric oxide-mediated maintenance of
      ion homeostasis and up-regulation of antioxidant defence in wheat seedling roots.
AB  - Salt stress induced an increase in endogenous carbon monoxide (CO) production and
      the activity of the CO synthetic enzyme haem oxygenase (HO) in wheat seedling
      roots. In addition, a 50% CO aqueous solution, applied daily, not only resulted
      in the enhancement of CO release, but led to a significant reversal in dry weight
      (DW) and water loss caused by 150 mm NaCl treatment, which was mimicked by the
      application of two nitric oxide (NO) donors sodium nitroprusside (SNP) and
      diethylenetriamine NO adduct (DETA/NO). Further analyses showed that CO, as well
      as SNP, apparently up-regulated H(+)-pump and antioxidant enzyme activities or
      related transcripts, thus resulting in the increase of K/Na ratio and the
      alleviation of oxidative damage. Whereas, the CO/NO scavenger haemoglobin (Hb),
      NO scavenger or synthetic inhibitor methylene blue (MB) or N(G)-nitro-l-arginine
      methyl ester hydrochloride (l-NAME) differentially blocked these effects.
      Furthermore, CO was able to mimic the effect of SNP by strongly increasing NO
      release in the root tips, whereas the CO-induced NO signal was quenched by the
      addition of l-NAME or cPTIO, the specific scavenger of NO. The results suggested
      that CO might confer an increased tolerance to salinity stress by maintaining ion
      homeostasis and enhancing antioxidant system parameters in wheat seedling roots,
      both of which were partially mediated by NO signal.

PMID- 18811736
TI  - Improving efficiency and value in health care: introduction.

PMID- 18811737
TI  - Generate both an impact factor and acceptance on Medline. Editorial.

PMID- 18811738
TI  - Intracranial thrombus extent predicts clinical outcome, final infarct size and
      hemorrhagic transformation in ischemic stroke: the clot burden score.
AB  - BACKGROUND: In ischemic stroke, functional outcomes vary depending on site of
      intracranial occlusion. We tested the prognostic value of a semiquantitative
      computed tomography angiography-based clot burden score. METHODS: Clot burden
      score allots major anterior circulation arteries 10 points for presence of
      contrast opacification on computed tomography angiography. Two points each are
      subtracted for thrombus preventing contrast opacification in the proximal M1,
      distal M1 or supraclinoid internal carotid artery and one point each for M2
      branches, A1 and infraclinoid internal carotid artery. We retrospectively studied
      patients with disabling neurological deficits (National Institute of Health
      Stroke Scale score >or=5) and computed tomography angiography within 24-hours
      from symptom onset. We analyzed percentages independent functional outcome
      (modified Rankin Scale score <or=2), final infarct Alberta Stroke Program Early
      Computed Tomography Score and parenchymal hematoma rates across categorized clot
      burden score groups and performed multivariable analysis. RESULTS: We identified
      263 patients (median age 73-years, National Institute of Health Stroke Scale
      score 10, onset-to-computed tomography angiography time 165 min). Clot burden
      score<10 was associated with reduced odds of independent functional outcome (odds
      ratio 0.09 for clot burden score<or=5; odds ratio 0.22 for clot burden score 6-7;
      odds ratio 0.48 for clot burden score 8-9; all versus clot burden score 10;
      P<0.02 for all). Lower clot burden scores were associated with lower follow-up
      Alberta Stroke Program Early Computed Tomography Scores (P<0.02 for all). Lower
      clot burden scores were associated with lower follow-up Alberta Stroke Program
      Early CT Scores (P<0.001) and higher parenchymal hematoma rates (P=0.008). Inter
      rater reliability for clot burden score was 0.87 (lower 95% confidence interval
      0.71) and intra-rater reliability 0.96 (lower 95% confidence interval 0.92).
      CONCLUSION: The quantification of intracranial thrombus extent with the clot
      burden score predicts functional outcome, final infarct size and parenchymal
      hematoma risk acutely. The score needs external validation and could be useful
      for patient stratification in stroke trials.

PMID- 18811739
TI  - Identification and management of polyvascular disease in patients with
      noncardioembolic ischaemic stroke.
AB  - Recent registry results have shown that polyvascular disease (PolyVD), usually
      manifested as coronary heart disease or peripheral arterial disease (PAD), is a
      marker of increased morbidity and mortality in patients with noncardioembolic
      ischaemic stroke, but is often inadequately assessed. This Personal View Paper
      advocates routine examination for PolyVD in such patients. Peripheral arterial
      disease can be readily detected in routine practice by measurement of the ankle
      brachial index. This paper makes recommendations for risk stratification,
      discharge documentation and, where possible, management of ischaemic stroke
      patients with PolyVD.

PMID- 18811740
TI  - Coated-platelets in ischemic stroke - potential insight into the etiology of
      stroke subtypes.

PMID- 18811741
TI  - Transient ischaemic attack is an emergency: think about best current stroke
      prevention options.

PMID- 18811742
TI  - Immune and inflammatory responses to stroke: good or bad?
AB  - Inflammatory and immune responses play important roles following ischaemic
      stroke. Inflammatory responses contribute to damage and also contribute to
      repair. Injury to tissue triggers an immune response. This is initiated through
      activation of the innate immune system. In stroke there is microglial activation.
      This is followed by an influx of lymphocytes and macrophages into the brain,
      triggered by production of pro-inflammatory cytokines. This inflammatory response
      contributes to further tissue injury. There is also a systemic immune response to
      stroke, and there is a degree of immunosuppression that may contribute to the
      stroke patient's risk of infection. This immunosuppressive response may also be
      protective, with regulatory lymphocytes producing cytokines and growth factors
      that are neuroprotective. The specific targets of the immune response after
      stroke are not known, and the details of the immune and inflammatory responses
      are only partly understood. The role of inflammation and immune responses after
      stroke is twofold. The immune system may contribute to damage after stroke, but
      may also contribute to repair processes. The possibility that some of the immune
      response after stroke may be neuroprotective is exciting and suggests that
      deliberate enhancement of these responses may be a therapeutic option.

PMID- 18811743
TI  - How much can be gained by more systematic prevention of stroke?
AB  - Clinical trials and observational studies provide evidence for a wide range of
      interventions of proven value for preventing a first or recurrent stroke. The
      available data indicate that strategies for primordial, primary and secondary
      stroke prevention are not being optimally implemented. Although specific
      estimates are difficult to calculate, the impact of improving the use of the wide
      array of effective stroke preventive interventions would be substantial.

PMID- 18811744
TI  - Molecular genetics of human intracranial aneurysms.
AB  - Intracranial aneurysms (IAs) are the dilatations of blood vessels in the brain
      and pose potential risk of rupture leading to subarachnoid hemorrhage. Although
      the genetic basis of IAs is poorly understood, it is well-known that genetic
      factors play an important part in the pathogenesis of IAs. Therefore, the
      identifying susceptible genetic variants might lead to the understanding of the
      mechanism of formation and rupture of IAs and might also lead to the development
      of a pharmacological therapy. To elucidate the molecular pathogenesis of diseases
      has become a crucial step in the development of new treatment strategies.
      Although extensive genetic research and its potential implications for future
      prevention of this often fatal condition are urgently needed, efforts to
      elucidate the susceptibility loci of IAs are hindered by the issues bewildering
      the most common and complex genetic disorders, such as low penetrance, late
      onset, and uncertain modes of inheritance. These efforts are further complicated
      by the fact that many IA lesions remain asymptomatic or go undiagnosed. In this
      review, we present and discuss the current status of genetic studies of IAs and
      we recommend comprehensive genome-wide association studies to identify genetic
      loci that underlie this complex disease.

PMID- 18811745
TI  - Stroke care development in Mainland China: past, present and future.
AB  - Stroke care in China was less developed than in western countries but great
      headway has been made in recent years through unremitting efforts by a group of
      local neurologists working in this field.

PMID- 18811746
TI  - The burden of stroke in Nigeria.
AB  - Stroke is a leading cause of morbidity and mortality worldwide, and it is likely
      to worsen in developing countries over the next two decades based on the
      projections by the World Health Organization (WHO). With the current scourge of
      HIV/AIDS and the battle against other communicable diseases like multi-drug
      resistant malaria and tuberculosis; Nigeria, the most populous black nation in
      the world, stands to risk the further straining of its resources as a result of
      the increasing prevalence of stroke and other cardiovascular diseases due to
      epidemiological transition. The current prevalence of stroke in Nigeria is 1.14
      per 1000 while the 30-day case fatality rate is as high as 40%. Management of the
      disease is largely conservative while there is little or no funding for high
      quality research. Primary prevention is the key to reducing the burden of the
      disease in a country with such poor resources.

PMID- 18811747
TI  - The burden of stroke in Pakistan.
AB  - Epidemiologic literature on stroke burden, patterns of stroke is almost non
      existent from Pakistan. However, several hospital-based case series on the
      subject are available, mainly published in local medical journals. Despite the
      fact that true stroke incidence and prevalence of stroke in Pakistan is not
      known, the burden is assumed to be high because of highly prevalent stroke risk
      factors (hypertension, diabetes mellitus, coronary artery disease, dyslipidemia
      and smoking) in the community. High burden of these conventional stroke risk
      factors is further compounded by lack of awareness, poor compliance hence poor
      control, and inappropriate management/treatment practices. In addition certain
      risk factors like rheumatic valvular heart disease may be more prevalent in
      Pakistan. We reviewed the existing literature on stroke risk factors in
      community, the risk factor prevalence among stroke patients, patterns of stroke,
      out come of stroke, availability of diagnostic services/facilities related to
      stroke and resources for stroke care in Pakistan.

PMID- 18811748
TI  - Retinal microvascular signs: a key to understanding the underlying
      pathophysiology of different stroke subtypes?
AB  - BACKGROUND: The heterogeneity of the pathology of stroke has been a major
      difficulty in assessing new treatments for acute stroke, and contributes to the
      complexity of stroke medicine. Some underlying mechanisms are poorly understood,
      such as small vessel (lacunar) disease. New technology such as advanced brain
      imaging has transformed our knowledge of large vessel disease and we suggest that
      other new technology such as detailed analysis of retinal vessels may provide new
      insights into the pathology of small vessel (lacunar) stroke disease. We
      hypothesise that retinal microvascular signs differ by pathological stroke
      subtype, and we plan to test this hypothesis in over 1000 acute stroke patients.
      SUMMARY: Eligible patients undergo a standardised neurological assessment
      followed by digital retinal photography. At a consensus meeting, an anatomical
      and aetiological classification is determined. Retinal photographs will be
      assessed qualitatively (e.g. retinal emboli, arteriovenous nicking) and
      quantitatively (arteriolar/venule ratio). Six-month vascular event rates together
      with disability and vital status are collected. CONCLUSION: Retinal vessel
      appearances may provide a 'window' to the brain and help determine the important
      underlying pathophysiological mechanisms of small vessel disease stroke.

PMID- 18811752
TI  - Nephrogenic systemic fibrosis and gadolinium: a cautionary tale in the molecular
      imaging era.

PMID- 18811753
TI  - Multidetector CT pulmonary angiography features of pulmonary embolus.
AB  - Pulmonary embolism (PE) is a life-threatening condition. Multidetector CT
      pulmonary angiography is currently the imaging method of choice for the detection
      of PE. The aim of this pictorial essay is to review the appearances of PE on
      multidetector CT pulmonary angiography, including signs that differentiate acute
      and chronic PE and markers of severity. The features of a non-diagnostic study
      and pitfalls leading to a false-positive or false-negative study are presented.

PMID- 18811754
TI  - MRI of sporadic Creutzfeldt-Jakob disease.
AB  - The key MRI findings in five cases of sporadic Creutzfeldt-Jakob disease (CJD)
      are illustrated with four 'definite' and one 'probable' according to World Health
      Organization criteria. Close attention to fluid-attenuation inversion recovery
      and diffusion-weighted imaging sequences are important for diagnosis, noting
      especially restricted diffusion in cortical and deep grey matter. Our study and
      those of others show predominant cortical, caudate and thalamic involvement. This
      pattern is highly sensitive and specific for the diagnosis. Fluid-attenuation
      inversion recovery and diffusion-weighted imaging signal abnormality becomes
      progressively more extensive and bilateral as disease progresses, but may become
      less pronounced in end-stage disease because of atrophy.

PMID- 18811755
TI  - Imaging of craniofacial fibrous dysplasia.
AB  - Fibrous dysplasia is a relatively common disorder of bone. It may affect the
      bones of the face and skull and, in so doing, produce a wide variety of clinical
      presentations. Plain film assessment of craniofacial fibrous dysplasia may be
      difficult because of varying appearances and complex, overlapping structures. The
      MRI appearances of fibrous dysplasia are often non-specific and may be confusing.
      Findings on CT are also variable, but more commonly lead to a specific diagnosis.
      This is because of the characteristic ground-glass appearance of woven bone, seen
      on CT in most if not all cases of craniofacial fibrous dysplasia.

PMID- 18811756
TI  - Diagnostic accuracy of CT angiography in acute gastrointestinal bleeding.
AB  - The aim of the study was to carry out a systematic review determining the
      accuracy of CT angiography in the diagnosis of acute gastrointestinal bleeding. A
      search of published work in Medline and manual searching of reference lists of
      articles was conducted. Studies were included if they compared CT angiography to
      a reference standard of upper gastrointestinal endoscopy, colonoscopy,
      angiography or surgery in the diagnosis of acute gastrointestinal bleeding. Eight
      published studies evaluating 129 patients were included. Data were used to form 2
      x 2 tables. Computed tomography angiography showed pooled sensitivity of 86% (95%
      confidence interval 78-92%) and specificity of 95% (95% confidence interval 76
      100%), without showing significant heterogeneity (chi(2) = 3.5, P = 0.6) and
      (chi(2) = 5.4, P = 0.6), respectively. Summary receiver operating characteristic
      analysis showed an area under the curve of 0.93. Computed tomography angiography
      is accurate in the diagnosis of acute gastrointestinal bleeding and can show the
      precise location and aetiology of bleeding, thereby directing further management.
      Strong recommendations for use of CT cannot be made from this review because of
      the methodological limitations and further large prospective studies are needed
      to define the role of CT in acute gastrointestinal bleeding.

PMID- 18811757
TI  - Nephrogenic systemic fibrosis and the role of gadolinium contrast media.
AB  - Nephrogenic system fibrosis is a rare disease affecting patients with severe
      renal insufficiency or dialysis. Its aetiology is incompletely understood.
      Evidence is growing that gadolinium contrast media is a major risk factor,
      whereby risk increases with larger cumulative doses. The role of other risk
      factors, such as inflammation or electrolyte disturbances, is less clear. All
      published cases to date received gadodiamide, gadopentetate or gadoversetamide,
      which are considered to be less stable due to a linear molecular structure. The
      aetiological significance of stability differences between the non-ionic linear,
      ionic linear and macrocyclic agents remains to be shown. For prevention, strict
      indications for MRI in risk patients can be combined with Food and Drug
      Administration (FDA) or European Medicines Agency (EMEA) guidelines. These
      recommend checking for renal impairment by history or laboratory tests. The FDA
      recommends avoidance of all gadolinium contrast media in patients with renal
      insufficiency grades 4 and 5 (glomerular filtration rate <30 mL/min per 1.73
      m(2)) or any grade of acute renal failure in liver transplantation patients or
      candidates. The EMEA differentiates between agents and advises avoidance of only
      gadodiamide and gadopentetate in the same patient categories. Other gadolinium
      contrast media should only be used after careful consideration of risks versus
      benefits. Post-procedural haemodialysis is only indicated in patients on regular
      dialysis.

PMID- 18811758
TI  - Functional CT in a rabbit model: evaluation of the perfusion characteristics
      before and after Ar-He cryoablation therapy.
AB  - The objective of this study was to investigate the perfusion characteristics of
      rabbit liver tumours before and after Ar-He (argon-helium) cryoablation using
      functional CT and to evaluate the therapeutic effect of Ar-He cryoablation. VX-2
      tumour was implanted into the livers of 30 New Zealand white rabbits. Two weeks
      after tumour implantation, Ar-He cryoablation was performed on these rabbits.
      Functional CT was performed on the rabbits before and after treatment on days 1,
      5, 14, 21 and 35. In the meantime, five rabbits were killed, and the livers were
      removed for histopathological examination at each of the time points mentioned
      above. Perfusion characteristics of the tumour and hot spot, such as blood flow
      (BF), blood volume (BV) and permeability, were analysed based on multislice CT.
      Histopathological studies corresponding to functional CT were observed, and the
      therapeutic effects (whether the tumour disappeared completely or still remained)
      were judged. The two-tailed student's t-test was used to compare the differences
      between the effect of pre- and post-Ar-He cryoablation treatment on tumour
      perfusion parameters. After cryoablation treatment, the number of tumours
      exhibiting complete necrosis was 13 (52%), and their perfusion parameters, such
      as BF, BV and permeability values, were significantly lower than those before
      treatment (P < 0.05, P < 0.01 and P < 0.05, respectively). After treatment, the
      number of incomplete necrotic tumours was 12 (48%). In the earlier stage (within
      14 days of treatment), the whole tumour perfusion parameters of BF, BV and
      permeability were significantly lower than those before treatment (P < 0.05). In
      the late stage (more than 14 days of treatment), the whole tumour perfusion
      parameters of BF, BV and permeability were not significantly different compared
      with the pretreatment results (P > 0.05). The hot spot perfusion parameters of
      incomplete necrotic tumours, such as BF, BV and permeability values, showed no
      significant differences compared with pretreatment (P > 0.05). Functional CT can
      measure the perfusion characteristics of hepatic tumours and is consistent with
      histopathological changes in the tumour after Ar-He cryoablation. Functional CT
      might also be accurate in judging the therapeutic effect of Ar-He cryoablation.

PMID- 18811759
TI  - Upright stereotactic vacuum-assisted needle biopsy of suspicious breast
      microcalcifications.
AB  - Stereotactic core needle biopsy is a useful technique for evaluation of
      suspicious breast microcalcifications. The development of the 11-G vacuum
      assisted biopsy system offers another method of minimally invasive biopsy carried
      out on a conventional mammography unit. We evaluate its usefulness, efficacy and
      safety in Asian women. Vacuum-assisted biopsy was carried out through the lateral
      approach using an add-on stereotactic device attached to a mammography unit. One
      hundred and five lesions were sampled in 97 patients. Excisional biopsy was
      subsequently Carried out for diagnosis of atypical ductal hyperplasia or
      carcinoma in high-risk patients. Patients with benign diagnosis underwent
      mammographic follow up. The technical success rate was 97%. An average of 13.5
      tissue cores were retrieved for each lesion. The histopathological result
      obtained from mammotome was benign in 84.8% and malignant in 15.2%. The benign
      microcalcifications were predominantly fibrocystic change (n = 42) whereas the
      malignant microcalcifications included ductal carcinoma in situ (n = 15) and
      invasive carcinoma (n = 1). Twenty-two patients underwent subsequent open
      surgical biopsy but no underestimation of disease was seen. Only two patients had
      vasovagal syncope and three others felt unwell during the biopsy. Nine patients
      had small haematomas, which resolved spontaneously. Vacuum-assisted biopsy
      carried out on an upright stereotactic mammography unit is a safe and effective
      method for evaluation of suspicious microcalcifications.

PMID- 18811760
TI  - Radiation protection to the eye and thyroid during diagnostic cerebral
      angiography: a phantom study.
AB  - We measured radiation doses to the eye and thyroid during diagnostic cerebral
      angiography to assess the effectiveness of bismuth and lead shields at dose
      reduction. Phantom head angiographic studies were performed with bismuth (study
      1) and lead shields (study 2). In study 1 (12 phantoms), thermoluminescent
      dosimeters (TLD) were placed over the eyes and thyroid in three groups: (i) no
      shields (four phantoms); (ii) anterior bismuth shields (four phantoms) and (iii)
      anterior and posterior bismuth shields (four phantoms). In a second study (eight
      phantoms), lead shields were placed over the thyroid only and TLD dose
      measurements obtained in two groups: (i) no shielding (four phantoms) and (ii)
      thyroid lead shielding (four phantoms). A standard 4-vessel cerebral angiogram
      was performed on each phantom. Study 1 (bismuth shields) showed higher doses to
      the eyes compared with thyroid (mean 13.03 vs 5.98 mSv, P < 0.001) and a higher
      eye dose on the X-ray tube side. Overall, the use of bismuth shielding did not
      significantly reduce dose to either eyes or thyroid in the measured TLD
      positions. In study 2, a significant thyroid dose reduction was found with the
      use of lead shields (47%, mean 2.46 vs 4.62 mSv, P < 0.001). Considerable doses
      to the eyes and thyroid highlight the need for increased awareness of patient
      protection. Eye shielding is impractical and interferes with diagnostic
      capability. Thyroid lead shielding yields significant protection to the thyroid,
      is not in the field of view and should be used routinely.

PMID- 18811761
TI  - Direct percutaneous puncture embolization of a peripancreatic pseudoaneurysm
      presenting with haemosuccus pancreaticus.
AB  - Haemosuccus pancreaticus is a rare cause of gastrointestinal haemorrhage. It is
      commonly due to a pseudoaneurysm in a setting of chronic pancreatitis. Treatment
      of aneurysms has traditionally been surgery; however, recently percutaneous
      radiological intervention has achieved good results with minimum morbidity and
      mortality. Transcatheter embolization of aneurysms is an effective treatment
      option. However, not all aneurysms are accessible through this route. We describe
      a technique of direct puncture embolization of a pseudoaneurysm causing
      haemosuccus pancreaticus.

PMID- 18811762
TI  - Small islet cell tumour in the pancreas: diagnostic value of diffusion-weighted
      MRI.
AB  - We present a case of a small islet cell tumour that was clearly depicted on
      diffusion-weighted imaging using a free breathing approach and discuss the
      diagnostic value of this sequence.

PMID- 18811763
TI  - Increased detections of leptomeningeal presentations in men with hormone
      refractory prostate cancer: an effect of improved systemic therapy?
AB  - Metastases from prostate cancer occur largely in bone through a haematogenous
      route. Metastatic spread of prostate cancer to the leptomeninges was rarely seen
      in the past. However, there has been a recent increase in presentations of
      leptomeningeal spread from prostate cancer in our institutions. Between 2004 and
      2006, four patients were diagnosed with metastatic prostate cancer with
      leptomeningeal metastases in our centres. All four patients had hormone
      refractory prostate cancer and had previously had chemotherapy. The median
      survival of these patients was approximately 15 months from the time of hormone
      refractoriness. The prognosis of leptomeningeal metastasis secondary to
      metastatic prostate cancer is poor, ranging from 2 to 7 months as seen in our
      series. New cases of leptomeningeal metastases seen in our series are
      hypothesized to be secondary to the use of effective modern systemic treatments.
      A parallel might be drawn with the increased rate of central nervous system
      metastases in breast cancer since the introduction of effective cytotoxic
      treatments and more recently targeted therapies. We suggest the clinicians to be
      aware of the potential change of natural history and pattern of progression in
      metastatic prostate cancer.

PMID- 18811764
TI  - Basal cell carcinoma of the nose: an Australian and New Zealand radiation
      oncology patterns-of-practice study.
AB  - Patients with a basal cell carcinoma (BCC) of the nose may be recommended
      radiotherapy (RT) with a wide variation in techniques and prescribed dose
      fractionation schedules between clinicians. The aim of this study was to
      ascertain variability in the patterns of practice among Australian and New
      Zealand radiation oncologists (ROs) when treating BCC arising on the nose. A
      postal survey was sent to 222 practising ANZ ROs detailing 12 different clinical
      scenarios of a BCC arising on the nose. The treatment selected for each scenario
      was analysed according to clinician's attitudes, training, experience and the
      availability of resources. The response rate was 74% (165/222) with 90
      respondents treating non-melanoma skin cancer. Training was perceived to have a
      marked influence on treatment practice by most (79%). In total, 72% of ROs were
      'very certain' in their choice of a dose fractionation schedule for obtaining
      local control and 61% for a satisfactory cosmetic outcome, respectively. Most
      (76%) favoured low-voltage photons over electrons as the optimal method of
      treatment, although for certain clinical scenarios most would use electrons. Dose
      fractionation schedules were highly variable with a lower total dose and
      hypofractionation favoured for older patients. Low-voltage photons were favoured
      for the T1 BCC and electrons for the T2 and T4 BCC. Nearly one-third of the ROs
      chose megavoltage photons for the T4 lesion. There is marked variation in
      treatment practices in terms of recommending RT over other treatment options, the
      choice of RT method, the dose fractionation schedule, the extent of field margins
      and the point of dose prescription.

PMID- 18811765
TI  - Phantom measurements and computed estimates of breast dose with radiotherapy for
      Hodgkin's lymphoma: dose reduction with the use of the involved field.
AB  - The risk of breast cancer following radiotherapy for Hodgkin's lymphoma appears
      to be dose related. In this study we compared breast dose in an anthropomorphic
      phantom for conventional 'mantle'; upper mediastinal/bilateral neck (minimantle)
      and unilateral neck fields, and evaluated the accuracy of computer planned dose
      estimates for out-of-field doses. For each field, computer-planned breast dose
      (CPD) estimates were compared with thermoluminescence dosimetry measurements in
      five locations within 'breast tissue'. CPD were also compared with ion chamber
      measurements in a slab phantom. Measured dose and CPD were within 20% of each
      other up to approximately 10 cm from the field edge. Beyond 10 cm, the CPD
      underestimated dose by a factor of 2 or more. The mini-mantle reduced the breast
      dose by a factor of approximately 10 compared with the mantle treatment. Treating
      the neck field lowered the breast dose by a further 50% or more. Modern involved
      field radiotherapy for lymphoma substantially reduces breast dose compared with
      mantle fields. Computer dosimetery underestimated dose at larger distances from
      the field. This needs to be considered if computer dosimetery is used to estimate
      breast dose and, by extrapolation, breast cancer risk.

PMID- 18811766
TI  - RANZCR 2006 peer review audit instrument.
AB  - The Royal Australian and New Zealand College Radiologists (RANZCR) continuing
      professional development programme incorporates audit with feedback as one
      important activity. The 2004 audit tool improves radiation oncologist practice
      quality; however, the instrument is designed to be regularly refined. To refine
      the 2004 audit tool and present the new instrument we incorporated comments and
      suggestions from: (i) the auditor and radiation oncologist from the single
      machine unit trial; (ii) members of RANZCR Post-Fellowship Education Committee;
      (iii) New South Wales Department of Health mandatory prescription requirements;
      and (iv) the International Atomic Energy Agency audit tool. In July 2006, the
      revised instrument was designed then endorsed by Post-Fellowship Education
      Committee. Important changes include: (i) combining criteria which separately
      scored documentation and correctness for similar items; (ii) scoring treatment
      schedule more explicitly; (iii) separating target volume coverage and critical
      structure dose; (iv) altering performance criteria scoring to be sensitive to
      peer review when no consensus can be reached; and (v) strengthening instructions
      for use and notes to improve comprehension and acceptance. The refined 2006
      instrument should be more user-friendly while increasing its usefulness.

PMID- 18811767
TI  - Importance of daily electronic portal imaging in radiotherapy.
AB  - An audit was conducted on 20 randomly selected patients who had daily electronic
      portal imaging during the course of their radiotherapy treatment. The daily
      images were reviewed to determine whether they were within tolerance according to
      departmental protocol. If they were not, the actions that were taken were
      documented. Four treatment areas (spine, chest, breast and prostate) were
      compared among five patients belonging to each of these categories. The patients
      were also categorized according to their treatment intent (radical or
      palliative). A total of 889 electronic portal images of 475 fractions were
      audited and 33.5% of all fractions were outside tolerance. It was found that 95%
      of patients needed an action during their treatment and 80% of the patients
      needed a treatment centre move during the course of their treatment. We found
      that errors occurred throughout the treatment and it was not possible to predict
      patients who could have daily imaging omitted. Concordance between radiation
      therapists and radiation oncologists for identification of error was also
      investigated. Despite the use of familiar electronic portal imaging protocols,
      image reviewers (radiation therapists and radiation oncologists) disagreed in
      interpretation 10% of the time. Our results support the hypothesis that daily
      imaging may be a useful tool for patients undergoing radiotherapy and that
      imaging may be ideally carried out before each fraction. Image assessments would
      be ideally carried out by a team approach, with all images reviewed by both
      radiation therapists and radiation oncologists. This approach has significant
      resource implications and may require review of current Medicare and Health
      Program Grant reimbursements.

PMID- 18811768
TI  - Planning and implementing an implanted fiducial programme for prostate cancer
      radiation therapy.
AB  - Using implanted gold seeds as fiducial markers to verify the position of the
      prostate in radiation therapy is well accepted and is becoming the standard of
      practice and requirement for international multicentre trials. In 2006 the
      decision was made at the Peter MacCallum Caner Centre (Peter Mac) to plan for and
      implement this process as standard clinical practice for radical dose prostate
      treatments (74-78 Gy). Before this, programme verification of field placement for
      prostate cancer radiation treatment was routinely carried out using regular off
      line electronic portal imaging with matching of bony anatomy. A small
      multidisciplinary team investigated and assisted in the implementation of this
      new practice across the Peter Mac sites at East Melbourne and our three satellite
      centres. Issues considered included seed size, number and position in the
      prostate, implant equipment, imaging equipment and procedure and consent and
      information forms. The use of a custom made fiducial pack, comprehensive patient
      information and a daily on-line imaging process was implemented. The experience
      of the first 28 patients at Peter Mac from January 2007 to May 2007 inclusive is
      reported on.

PMID- 18811771
TI  - Preventing women's sexual risk behaviors during travel.
AB  - Sexually transmitted infections (STIs) are a global concern. Although several
      countries have tracked the incidence of STIs acquired during travel to foreign
      countries, the United States lags behind in this practice. Nevertheless, there is
      evidence from the US and several countries that women engage in sexual risk
      behaviors during travel whether domestic or foreign, thereby placing themselves
      at risk for contracting STIs. Guidelines for assessment, prevention, and travel
      related supplies and resources are discussed.

PMID- 18811772
TI  - The parental experience of pregnancy after perinatal loss.
AB  - OBJECTIVE: To review the research literature on the parental experience of
      pregnancy, primarily maternal, subsequent to perinatal loss. DATA SOURCES:
      Computerized searches on CINAHL and PubMed databases. STUDY SELECTION: Articles
      from indexed journals relevant to the objective were reviewed from January 1997
      to December 2007. Only research-based studies in English were included. DATA
      EXTRACTION: The review was performed using the methodology of Whittemore and
      Knafl (2005). Data were extracted and organized under headings:
      author/year/setting; purpose; sample; design/instruments; results; and nursing
      implications for parents during a pregnancy following a perinatal loss. DATA
      SYNTHESIS: Depression and anxiety are frequently seen in pregnant women
      subsequent to a perinatal loss. The parental experience is filled with intense
      and conflicting emotions as parents balance being hopeful while worrying about
      another potential loss. CONCLUSIONS: It is important for health care providers to
      evaluate the woman's obstetric history, acknowledge and validate previous
      perinatal loss, and discuss with her what would be helpful during the prenatal
      period with respect to the previous perinatal loss.

PMID- 18811773
TI  - Stress and preterm labor and birth in Black women.
AB  - OBJECTIVE: To examine (a) 3 commonly used measures of stress during pregnancy,
      (b) changes in stress over time to determine when stress is highest, and (c)
      whether any of the stress measures predict who will deliver preterm in pregnant
      Black women. DESIGN: Prospective descriptive study. SETTING: Perinatal evaluation
      center and outpatient clinics of a teaching hospital in the northeast.
      PARTICIPANTS: Fifty-nine Black women: 39 were recruited in preterm labor from a
      Perinatal Evaluation Center, and 20 experiencing healthy pregnancies were
      recruited from the prenatal clinic. MEASURES: Stress was measured using 2 paper
      and pencil tests (the Prenatal Distress Questionnaire and the Perceived Stress
      Scale) and corticotropin-releasing hormone. RESULTS: There was not a high
      correlation between stress measures. Stress at 28 weeks as measured by Prenatal
      Distress Questionnaire and Perceived Stress Scale was at its highest, but
      corticotropin-releasing hormone increased to 32 weeks and then decreased.
      CONCLUSIONS: Perceived stress, prenatal distress, and corticotropin-releasing
      hormone do not all appear to be measuring the same phenomenon. Screening for
      stress in Black women at 28 weeks requires further research as perceived stress
      levels in Black women experiencing preterm labor around 28 weeks differentiated
      women who delivered preterm infants from Black women who delivered at term.

PMID- 18811774
TI  - The relationship between breastfeeding self-efficacy and perceived insufficient
      milk among Japanese mothers.
AB  - OBJECTIVE: To examine the relationship between maternal perceptions of
      insufficient milk and breastfeeding confidence using the Breastfeeding Self
      Efficacy Scale. DESIGN: Cross-sectional study. PARTICIPANTS: Two hundred and
      sixty-two in-hospital breastfeeding mothers in Japan. MAIN OUTCOME MEASURE:
      Breastfeeding self-efficacy was measured in-hospital and perception of
      insufficient milk was measured at 4 weeks postpartum. RESULTS: Although most
      mothers intended to exclusively breastfeed, less than 40% were doing so at 4
      weeks postpartum. Among the mothers using formula, 73% cited perceived
      insufficient milk as the primary reason for supplementation or completely
      discontinuing breastfeeding. Mothers' perception of insufficient milk at 4 weeks
      postpartum were significantly related to breastfeeding self-efficacy in hospital
      in the immediate postpartum period (r=.45, p<.001). Hierarchical multiple
      regression revealed that breastfeeding self-efficacy explained 21% of the
      variance in maternal perceptions of insufficient milk, and the contribution was
      independent of sociodemographic variables. CONCLUSIONS: Enhancing breastfeeding
      self-efficacy in the immediate postpartum period may reduce maternal perceptions
      of insufficient milk and the premature discontinuation or supplementation of
      breastfeeding. Additional research is warranted.

PMID- 18811775
TI  - The role of social support in helping Chinese women with perinatal depressive
      symptoms cope with family conflict.
AB  - PURPOSE: To investigate the role of social support (direct, moderating, and/or
      mediating effects) in mitigating the stressors (marital conflicts and/or
      conflicts with parents-in-law) that are associated with perinatal depressive
      symptoms. DESIGN: A 3 stage (second trimester, third trimester and postpartum),
      prospective, longitudinal study. PARTICIPANTS: A total of 2,365 women were
      recruited with systematic sampling from 6 regional public hospitals in Hong Kong.
      OUTCOME MEASURES: The Interpersonal Support Evaluation List was used to measure
      the functional aspects of the perceived availability of social support. The women
      were identified as having depressive symptoms using the Edinburgh Postnatal
      Depression Scale. Marital conflict and conflict with parents-in-law were
      investigated using the Dyadic Adjustment Scale and the Stryker Adjustment
      Checklist, respectively. RESULTS: Social support was consistently found to have
      direct effects in the 3 stages of the perinatal period. It was also found to have
      a moderating effect on the relationship between antenatal depressive symptoms and
      marital and mother-in-law conflicts and on postnatal depressive symptoms in
      conflicts with father-in-law and to play a mediating role in the relationship
      between marital and mother-in-law conflicts and postnatal depressive symptoms.
      CONCLUSIONS: These findings provide important information about the role of
      social support related to antenatal and postnatal depressive symptoms among the
      Hong Kong Chinese population.

PMID- 18811776
TI  - Cervical cancer screening practices among university women.
AB  - OBJECTIVE: To assess predictors of young women's intentions to be screened for
      cervical cancer. DESIGN: A descriptive, correlational, cross-sectional study
      using the Theory of Planned Behavior (TPB). PARTICIPANTS: A total of 904 young
      women (mean age=20.7 years; SD=1.77) participated in an online cervical cancer
      screening survey. METHOD: A web-based survey (WebCT) was used to survey young
      women, 25 years of age or less, attending a university in eastern Canada.
      Descriptive, correlational, and logistic regression statistics were calculated.
      RESULTS: Findings indicated that social norms (perceptions about whether or not
      people close to them think Pap screening is important) and perceived behavioral
      control (perceptions about personal resources or barriers to receiving a Pap
      test) were significantly related to young women's intentions to be screened.
      CONCLUSION: Strategies to promote cervical cancer screening among young
      university women need to recognize the impact of social norms and perceived
      barriers on Pap screening intentions in this population.

PMID- 18811778
TI  - Responding to women's HIV and STI risk in the developing world.

PMID- 18811779
TI  - Effects of HIV/AIDS on maternity care providers in Kenya.
AB  - OBJECTIVE: To explore the impact of HIV/AIDS on maternity care providers in labor
      and delivery in a high HIV-prevalence setting in sub-Saharan Africa. DESIGN:
      Qualitative one-on-one in-depth interviews with maternity care providers.
      SETTING: Four health facilities providing labor and delivery services (2 public
      hospitals, a public health center, and a small private maternity hospital) in
      Kisumu, Nyanza Province, Kenya. PARTICIPANTS: Eighteen maternity care providers,
      including 14 nurse/midwives, 2 physician assistants, and 2 physicians (ob/gyn
      specialists). RESULTS: The HIV/AIDS epidemic has had numerous adverse effects and
      a few positive effects on maternity care providers in this setting. Adverse
      effects include reductions in the number of health care providers, increased
      workload, burnout, reduced availability of services in small health facilities
      when workers are absent due to attending HIV/AIDS training programs, difficulties
      with confidentiality and unwanted disclosure, and maternity care providers' fears
      of becoming HIV infected and the resulting stigma and discrimination. Positive
      effects include improved infection control procedures on maternity wards and
      enhanced maternity care provider knowledge and skills. CONCLUSION: A multifaceted
      package including policy, infrastructure, and training interventions is needed to
      support maternity care providers in these settings and ensure that they are able
      to perform their critical roles in maternal healthcare and prevention of HIV/AIDS
      transmission.

PMID- 18811780
TI  - The condom divide: disenfranchisement of Malawi women by church and state.
AB  - OBJECTIVE: To examine the impact of 2 mitigating social institutions, religious
      organizations, and the state, on Malawi women's vulnerability to HIV. DESIGN: In
      depth interviews with a purposive sample of 40 central leaders from 5 faith-based
      organizations in Malawi were recorded and transcribed as part of an on-going
      larger study. Qualitative description was used to identify themes and categories.
      SETTING: Primarily urban and periurban areas of south-central Malawi.
      PARTICIPANTS: A minimum of 6 leaders from each faith-based organization were
      interviewed; the mean age of the primarily male (68%) participants was 44 years
      (range 26-74). RESULTS: Analysis of religious leaders' messages about HIV
      produced an overarching theme, the condom divide, which conceptualized the
      divergence between faith-based organizations and the state's prevention messages
      related to HIV prevention strategies. CONCLUSION: Faith-based organizations have
      "demonized" state messages about condoms as promoting sin. The faith-based
      organizations' insistence on abstinence and faithfulness leaves women with few
      options to protect themselves. As socially conscious citizens of the world,
      nurses can increase the responsiveness to the disparate levels of suffering and
      death in countries like Malawi.

PMID- 18811781
TI  - Attitudes and practices of obstetric care providers in Kabul, Afghanistan
      regarding antenatal testing for sexually transmitted infection.
AB  - OBJECTIVE: To determine attitudes toward and utilization of testing for HIV,
      syphilis, and hepatitis B among obstetric care providers in Kabul, Afghanistan.
      DESIGN: Cross-sectional survey. SETTING: Three public maternity hospitals in
      Kabul, Afghanistan. PARTICIPANTS: One hundred and fourteen (114) doctors and
      midwives. MAIN OUTCOME MEASURE: Prevalence and correlates of ever having tested
      patients for HIV, syphilis, and hepatitis B and agreement with statements
      concerning attitudes toward testing and care. RESULTS: Less than half of the
      patient care providers surveyed had previously tested a patient for HIV,
      syphilis, or hepatitis B. Presumed rarity of these infections in Afghanistan was
      the most frequently stated reason for not testing, although many midwives stated
      that they did not have the authority to order tests. Most providers supported
      testing to promote neonatal health, but some midwives expressed concern regarding
      patient and family perceptions. CONCLUSIONS: Due to logistical and cultural
      barriers, obstetric care providers underutilize testing for antenatal patients in
      Afghanistan. Improved training, empowerment of female providers, and availability
      of rapid testing are needed.

PMID- 18811783
TI  - Redefining and developing exotic animal medicine.

PMID- 18811785
TI  - Proximal femoral focal deficiency (PFFD) in a young Doberman pinscher.

PMID- 18811787
TI  - Canine African trypanosoma.

PMID- 18811790
TI  - Infants admitted to neonatal units--interventions to improve breastfeeding
      outcomes: a systematic review 1990-2007.
AB  - This review aimed to identify interventions to promote breastfeeding or breast
      milk feeding for infants admitted to the neonatal unit. The medical electronic
      databases were searched for papers listed between 1990 and June 2005 which had
      breastfeeding or breast milk as an outcome and which targeted infants who had
      been admitted to a neonatal unit, thus including the infant and/or their parents
      and/or neonatal unit staff. Only papers culturally relevant to the UK were
      included resulting in studies from the USA, Canada, Europe, Australia and New
      Zealand. This search was updated in December 2007 to include publications up to
      this date. We assessed 86 papers in full, of which 27 ultimately fulfilled the
      inclusion criteria. The studies employed a range of methods and targeted
      different aspects of breastfeeding in the neonatal unit. Variations in study type
      and outcomes meant that there was no clear message of what works best but skin-to
      skin contact and additional postnatal support seemed to offer greater advantage
      for the infant in terms of breastfeeding outcome. Galactogogues for mothers who
      are unable to meet their infants' needs may also help to increase milk supply.
      Evidence of an effect from other practices, such as cup-feeding on breastfeeding
      was limited; mainly because of a lack of research but also because few studies
      followed up the population beyond discharge from the unit. Further research is
      required to explore the barriers to breastfeeding in this vulnerable population
      and to identify appropriate interventions to improve breastfeeding outcomes.

PMID- 18811791
TI  - The relationship between personal breastfeeding experience and the breastfeeding
      attitudes, knowledge, confidence and effectiveness of Australian GP registrars.
AB  - In conjunction with other health professionals, doctors believe they play an
      important role in promoting breastfeeding to women. Although many have positive
      breastfeeding attitudes, significant knowledge deficits often limit their
      capacity to effectively encourage, support and assist breastfeeding women and
      their infants. Personal breastfeeding experience (of self or partner) may be the
      main source of breastfeeding knowledge and skill development and is related to
      improved knowledge, more positive attitudes and greater confidence. This paper
      describes the relationship between the cumulative length of personal
      breastfeeding experience and the breastfeeding knowledge and attitudes of a
      cohort of Australian general practice (GP) registrars, as well as their
      confidence and perceived effectiveness assisting breastfeeding women. The
      Australian Breastfeeding Knowledge and Attitude Questionnaire containing
      demographic items, a 20-item attitude scale and a 40-item knowledge scale was
      distributed between February and May 2007 to Australian GP registrars in their
      final year of training. Participants with more than 52-week cumulative personal
      (self or partner) breastfeeding experience had the highest mean knowledge score,
      had more positive attitudes, and were more confident and effective than all other
      participants. Parents with limited personal experience (<or=26 weeks) had the
      poorest breastfeeding attitudes and their knowledge base was similar to
      participants with no personal experience. Confidence and perceived effectiveness
      when assisting breastfeeding women rose with increasing cumulative breastfeeding
      experience. Personal breastfeeding experience per se does not guarantee better
      breastfeeding knowledge or attitudes although increasing length of experience is
      related to higher knowledge, attitude, confidence and perceived effectiveness
      scores.

PMID- 18811792
TI  - Effectiveness of a community-based responsive feeding programme in rural
      Bangladesh: a cluster randomized field trial.
AB  - Responsive complementary feeding, whereby the mother feeds her child in response
      to child cues of hunger state and psychomotor abilities, is a problem in some
      countries, and likely contributes to malnutrition. Interventions are needed to
      evaluate whether promoting responsive feeding would add any benefit. Using a
      cluster randomized field trial, we evaluated a six-session educational programme
      that emphasized practice of two key behaviours, namely child self-feeding and
      maternal responsiveness. One hundred mothers and their 12- to 24-month-olds
      attended the sessions as part of village clusters randomly assigned to the
      intervention group. A similar number of controls received sessions on foods to
      feed and nutritional disorders. Outcomes assessed at pre-test, 2-week post
      intervention and again 5-months post-intervention included weight, mouthfuls of
      food taken, self-feeding and maternal responsiveness. Research assistants, blind
      to group assignment, observed and coded mother and child behaviours during the
      midday meal. Secondary measures included foods fed and feeding messages recalled.
      Analysis was based on intention to treat and accounted for clustering. Only 10%
      of each group was lost to follow-up. Weight (d = 0.28), weight gain (d = 0.48)
      and child self-feeding (d = 0.30) were significantly higher in the responsive
      feeding group. Mouthfuls of food eaten and maternal responsiveness were not
      significantly increased by the intervention. Mothers in the intervention gave
      their children more vegetables, and spontaneously recalled more feeding messages
      at the 5-month follow-up. These results provide evidence that self-feeding and
      weight gain can improve by targeting specific behaviours, while maternal
      responsiveness may require more intensive strategies.

PMID- 18811793
TI  - Perceived parenting behaviours predict young adolescents' nutritional intake and
      body fatness.
AB  - This study investigated whether perceptions of parenting behaviours predict young
      adolescents' nutritional intake and body fatness. The randomly selected study
      sample consisted of 106 13-15 years olds from Houston Metropolitan Statistical
      Area. Parenting style variables were created by cluster analysis and factor
      analysis. A two-cluster solution for both maternal and paternal parenting style
      represented authoritative vs. non-authoritative parenting. Two parenting
      dimension factors derived were maternal/paternal nurturing and control. For
      adolescents' energy and nutrient intake, greater maternal nurturing appeared to
      be most beneficial given its association with lower consumption of total
      kilocalorie and lower saturated fat intake. Paternal nurturing was associated
      with lower sodium intake, whereas paternal control predicted lower percentage of
      kilocalories from carbohydrate and percentage Dietary Reference Intake for
      dietary fibre, and greater percentage of kilocalories from total fat. Maternal
      authoritative parenting and lower maternal control over their adolescents may
      have protective effects against having heavier and fatter adolescents given their
      associations with adolescents' body weight, sub-scapular skinfold, waist
      circumference, body mass index, and the tendencies of being at risk of overweight
      and being overweight. None of paternal parenting styles or dimensions appeared to
      be significantly related to adolescents' body fatness.

PMID- 18811794
TI  - Percent body fat, skinfold thickness or body mass index for defining obesity or
      overweight, as a risk factor for asthma in schoolchildren: which one to use in
      epidemiological studies?
AB  - None of the epidemiological studies indicating that obesity is a risk factor for
      asthma in schoolchildren have used the percent body fat (PBF) to define obesity.
      The present study compares the definition of obesity using body mass index (BMI),
      PBF and the raw sum of the thickness of four skinfolds (SFT) to evaluate this
      condition as a risk factor for asthma. All classes of children of the target ages
      of 6-8 years of all schools in four municipalities of Murcia (Spain) were
      surveyed. Participation rate was 70.2% and the number of children included in the
      study was 931. Height, weight and SFT (biceps, triceps, subscapular and
      suprailiac) were measured according to standard procedures. Current active asthma
      was defined from several questions of the International Study of Asthma and
      Allergies in Childhood questionnaire. Obesity was defined using two standard cut
      off points for BMI and PBF, and the 85th percentile for BMI, PBF and SFT. The
      highest quartile of each type of measurement was also compared with the lowest. A
      multiple logistic regression analysis was made for the various obesity
      definitions, adjusting for age, asthma in the mother and father and gender. The
      adjusted odds ratios of having asthma among obese children were different for
      boys and girls and varied across the different obesity definitions. For the
      standard cut-off points of BMI they were 1.19 [95% confidence interval (CI) 0.41
      3.43] for girls and 2.00 (95% CI 0.97-4.10) for boys; however, for PBF (boys 25%,
      girls 30%) the corresponding figures were 1.54 (95% CI 0.63-3.73) and 1.20 (95%
      CI 0.66-2.21). BMI, PBF and SFT showed more consistency between each other when
      using the other cut-off points. BMI, PBF (except standard cut-off points) and SFT
      produce relatively comparable results when analysing the interaction between
      obesity and asthma.

PMID- 18811797
TI  - Scaling-up evaluation of field functioning of arbuscular mycorrhizal fungi.

PMID- 18811798
TI  - Resolving uncertainty in the carbon economy of mycorrhizal fungi.

PMID- 18811799
TI  - Arsenic-eaters: by accident or by design.

PMID- 18811800
TI  - The Fidelis recall: how much pressure can the ICD world bear?

PMID- 18811801
TI  - Clinical judgment versus decision analysis for managing device advisories.
AB  - INTRODUCTION: Implantable cardioverter-defibrillator (ICD) and pacemaker (PM)
      advisories may have a significant impact on patient management. Surveys of
      clinical practice have shown a great deal of variability in patient management
      after a device advisory. We compared our management of consecutive patients in a
      single large university practice with device advisories to the "best" patient
      management strategy predicted by a decision analysis model. METHODS: We performed
      a retrospective review of all patients who had implanted devices affected by an
      advisory at our medical center between March 2005 and May 2006 and compared our
      actual patient management strategy with that subsequently predicted by a decision
      analysis model. RESULTS: Over 14 months, 11 advisories from three different
      manufacturers affected 436 patients. Twelve patients (2.8%) were deceased and 39
      patients (8.9%) were followed at outside facilities. Management of the 385
      remaining patients varied based on type of malfunction or potential malfunction,
      manufacturer recommendations, device dependency, and patient or physician
      preferences. Management consisted of the following: 57 device replacements
      (15.2%), 44 devices reprogrammed or magnets issued (11.7%), and 268 patients
      underwent more frequent follow-up (71.3%). No major complications, related to
      device malfunction or device replacement, occurred among any patient affected
      with a device advisory. Concordance between the decision analysis model and our
      management strategy occurred in 57.1% of cases and 25 devices were replaced when
      it was not the preferred treatment strategy predicted by the decision model
      (43.9%, 37.3% when excluding devices replaced based on patient preference). The
      decision analysis favored replacement for all patients with PM dependency, but
      only for four patients with ICDs for secondary prevention. No devices were left
      implanted that the decision analysis model predicted should have been replaced.
      CONCLUSIONS: We found that despite a fairly conservative device replacement
      strategy for advisories, we still replaced more devices when it was not the
      preferred device management strategy predicted by a decision analysis model. This
      study demonstrates that even when risks and benefits are being considered by
      experienced clinicians, a formal decision analysis can help to develop a
      systematic evidence based approach and potentially avoid unnecessary procedures.

PMID- 18811802
TI  - Cardiac biomarkers in patients with permanent pacemakers and implantable
      cardioverter-defibrillators undergoing an MRI scan.
AB  - BACKGROUND: Recent series suggest that magnetic resonance imaging (MRI) scanning
      can be performed safely in select patients with pacemakers or implantable
      cardioverter-defibrillators (ICDs). Limited data have been reported on cardiac
      biomarker release following MRI scans in patients with pacemakers. The current
      study evaluated cardiac biomarkers pre- and postscan in patients with permanent
      pacemakers or ICDs undergoing MRI scanning of any body region without peak
      specific absorption rate (SAR) limit. METHODS: Thirty-seven patients with a total
      of 75 leads underwent a total of 40 MRI scans of both truncal and nontruncal
      regions using usual protocols with standard peak SAR settings for the scan. No
      patient was pacemaker dependent. Pacemaker magnet mode and ICD therapy were
      disabled during the scan. Baseline cardiac troponin-I and myoglobin levels were
      obtained immediate pre- and 6-12 hours postscan. Pacemaker capture thresholds
      were measured immediately pre- and postscan. RESULTS: The median peak SAR was 2.4
      (1.3, 3.2) W/kg for all scans. Cardiac troponin-I was unchanged following an MRI
      scan (0.01 (0.01, 0.02) versus 0.01 (0.01, 0.02) ng/mL, P = 0.90). Capture
      thresholds were no different pre- and postscan (0.67 (0.50, 0.80) versus 0.70
      (0.50, 0.79) V at 0.5 ms, P = 0.50). CONCLUSIONS: The current series suggests
      that an MRI scan may be performed safely in carefully selected patients with
      close monitoring during the scan without limitation on peak SAR level or body
      landmark. Furthermore, it is unlikely that an MRI scan will produce sufficient
      tissue heating to cause enough myocardial cell necrosis to result in cardiac
      biomarker release.

PMID- 18811803
TI  - Ventricular arrhythmias after left ventricular assist device implantation.
AB  - BACKGROUND: Left ventricular assist devices (LVADs) have been used as a bridge to
      cardiac transplantation and as destination therapy in patients with advanced
      heart failure. The period after LVAD support is associated with ventricular
      arrhythmias (VAs) despite ventricular unloading and such VAs can have a
      detrimental effect on survival. Despite the increasing use of LVAD, little is
      known regarding post-LVAD VAs at the molecular level and in vivo. METHODS: Forty
      two patients who received LVAD over a 24-month period were evaluated and grouped
      on the basis of the presence or absence of VAs during LVAD support. We completed
      a comparative microarray analyses between six patients who developed ventricular
      tachycardia (VT) or ventricular fibrillation (VF) after LVAD support and six
      patients who did not develop VAs after LVAD. RESULTS: VAs occurred in 15 patients
      (35.7%) during LVAD support at a median post-LVAD day of 25.2. VAs were strongly
      associated with nonusage of a beta-blocker post-LVAD (odds ratio of 7.04, P-value
      = 0.001). Analysis of a subset of patients who had VT or VF after LVAD placement
      showed a decrease in the expression of connexin 43 (0.48 +/- 0.07), Na+/K+-ATPase
      (0.60 +/- 0.05), and voltage-gated K+ channel Kv4.3 (0.42 +/- 0.04), and an
      increase in Na+/Ca2+ exchanger (2.2 +/- 0.4) and the structural genes: Titin (2.1
      +/- 0.2), laminin (1.7 +/- 0.4), calsequestrin (1.8 +/- 0.5), skeletal muscle
      isoform of troponin T (5.1 +/- 0.9), and skeletal muscle isoform of troponin I
      (3.9 +/- 0.7). CONCLUSION: After LVAD, the increased risk of VAs is strongly
      associated with nonusage of beta-blocker postoperatively.

PMID- 18811804
TI  - Circadian rhythm of appropriate implantable cardioverter defibrillator discharges
      in patients with hypertrophic cardiomyopathy.
AB  - AIMS: To characterize the circadian pattern of implantable cardioverter
      defibrillators (ICD) discharges in patients with hypertrophic cardiomyopathy
      (HCM) without previous surgical myectomy or percutaneous alcohol septal ablation.
      METHODS AND RESULTS: HCM patients without previous surgical myectomy or
      percutaneous alcohol septal ablation having undergone ICD insertion at Mayo
      Clinic from 1992 to 2005 were studied. Analysis of appropriate ICD discharges
      with respect to time of day was performed. During a mean follow-up of 4.4 +/- 4
      years (P = 0.02), a total of 122 appropriate discharges were recorded. The
      average event rate for this group of patients was 4.3% per year. The circadian
      pattern reveals a pronounced peak in ICD discharges for the hours from 14:00 to
      16:00. HCM patients receiving antiarrhythmic or beta-blocker therapy did not
      demonstrate a different circadian pattern compared with patients not receiving
      these medications. CONCLUSION: Analysis of the temporal distribution of ICD
      discharges in HCM patients without previous surgical myectomy or percutaneous
      alcohol septal ablation reveals a peak occurrence of ICD discharges during the
      period from 12:00 to 18:00 hours with the highest incidence between 14:00 and
      16:00 hours. This is different from the well-documented early morning peak
      observed in ischemic dilated cardiomyopathy patients.

PMID- 18811805
TI  - Remote monitoring of CRT-ICD: the multicenter Italian CareLink evaluation--ease
      of use, acceptance, and organizational implications.
AB  - PURPOSE: The Medtronic CareLink allows remote implantable device follow-up. In
      this first European experience with CareLink, we assessed the ease of use of the
      system, the acceptance, and satisfaction of patients and clinicians. METHODS:
      Patients implanted with biventricular defibrillators for more than 6 months
      received the CareLink monitor and were trained to perform home device
      interrogation and transmission. Patient and clinician experience and preference
      were evaluated through specific questionnaires. RESULTS: Sixty-seven patients
      were enrolled and were able to perform data transmissions during the 3-month
      study duration. The overall duration of interrogation procedure was 7 +/- 5
      minutes, and frequently the procedure did not require the assistance of a
      caregiver. Patients reported a general preference for remote versus in-clinic
      follow-up and described a sense of reassurance created by the remote monitoring
      capability.In the centers, the review procedure was successful; its mean duration
      was 5 +/- 2 minutes per transmission and the users indicated that the access and
      navigation of the review website were easy. At the end of the evaluation, the
      data available for remote review were judged complete and adequate to provide
      almost the same standard of care as that offered in traditional in-clinic visit.
      In general, the remote monitoring was seen as a potential tool to improve the
      clinical management of patients with device. CONCLUSIONS: The ease of use,
      satisfaction, and acceptance of the CareLink Network in European clinical
      practice appears elevated both for patients and for clinicians.

PMID- 18811806
TI  - Hemodynamics and prognosis after primary cardiac resynchronization system
      implantation compared to "upgrade" procedures.
AB  - INTRODUCTION: Left bundle brunch block (LBBB) and right ventricular stimulation
      (RVS) may be associated with asynchrony and heart failure. Differences between
      these two entities and their response to cardiac resynchronization therapy (CRT)
      are not well defined. METHODS: Patients receiving CRT from 1999 to 2006 were
      analyzed for cardiac events and prognosis separated between primary implants for
      LBBB (n = 221) and upgrades from RVS (n = 107). A subgroup of 105 patients (LBBB
      = 69; RVS = 36) was studied in more detail (New York Heart Association [NYHA],
      quality of life, brain natriuretic peptide, peak VO2, left ventricular ejection
      fraction [LVEF], wedge pressure, Cardiac Index, QRS, left-right preejection
      period using pulsed wave doppler, septum-lateral wall motion delay using tissue
      doppler imaging) at baseline and after 1 year. RESULTS: Age (68.4 +/- 11 years vs
      68.7 +/- 15 years, n. s.), NYHA class (3.1 vs 3.1, n. s.), LVEF (26.4 vs 28.1, n.
      s.), and clinical parameters were comparable between LBBB and RVS. The latter
      group consisted of more patients with chronic atrial fibrillation (14% vs 37%, P
      = 0.03). After 1 year, NYHA class (-0.8 +/- 0.8 vs -0.6 +/- 0.8, n. s.), LVEF
      (+13.7 +/- 14% vs +8.7 +/- 10%, n. s.), and clinical parameters improved
      similarly. After a median follow-up of 2.33 +/- 1.8 years in the LBBB versus 2.43
      +/- 1.9 years in the RVS group, there was no difference in long-term prognosis or
      cardiac events in the total cohort (5-year event rate, 53% vs 55%, P = n. s.).
      CONCLUSION: Upgrade patients showed similar baseline parameters and response to
      CRT as to primary implants. No difference in events or long-term prognosis could
      be observed.

PMID- 18811807
TI  - Long-term prognostic value of baseline C-reactive protein in predicting
      recurrence of atrial fibrillation after electrical cardioversion.
AB  - BACKGROUND: An increasing body of evidence links atrial fibrillation (AF) to the
      inflammatory state. It has been suggested that increased C-reactive protein (CRP)
      levels are associated with greater risk of AF recurrence at short- and mid-term.
      OBJECTIVE: We sought to investigate the association between CRP and long-term
      risk of AF recurrence. METHODS: This was a prospective observational study. We
      investigated the association between baseline CRP levels and recurrence of AF
      over a 3-year follow-up period after successful electrical cardioversion (EC). A
      total of 60 patients were studied (mean age: 68.4 +/- 7.2 years, 60% men). All
      patients were receiving amiodarone for sinus rhythm maintenance. We further
      divided the study population into three tertiles according to the values of
      baseline CRP (tertile 1: <0.43 mg/dL; tertile 2: 0.43-0.8 mg/dL; tertile 3: >0.8
      mg/dL). RESULTS: Overall, 75% of patients relapsed into AF during the 3-year
      study period. AF recurrence was significantly lower in the 1st CRP tertile group
      (P = 0.039). The Kaplan-Meier survival analysis showed that the rate of AF
      recurrence was significantly lower in the lowest CRP tertile (log rank; P <
      0.001). In a multivariable Cox regression model adjusted for other potential
      covariates, only CRP (upper two tertiles) was an independent predictor of AF
      recurrence (heart rate: 6.3, 95% confidence interval: 3.1-12.7, P < 0.001).
      CONCLUSIONS: Our findings suggest that baseline CRP levels before EC have an
      independent prognostic value in predicting the long-term risk of AF recurrence.

PMID- 18811808
TI  - Arrhythmic risk evaluation during exercise at high altitude in healthy subjects:
      role of microvolt T-wave alternans.
AB  - BACKGROUND: Altitude-induced sympathetic hyperactivity can elicit rhythm
      disturbances in healthy subjects, in particular during exercise. AIM: To asses
      the real susceptibility of healthy myocardium to malignant ventricular
      arrhythmias during exercise at high altitude using microvolt T-wave alternans
      (MTWA). METHODS: We evaluated eight healthy trained participants (one female, 42
      +/- 9 years) during a mountain climbing expedition on Gashembrum II (Pakistan,
      8,150 m). MTWA and heart rate variability (HRV) were measured in each subject at
      sea level and at high altitude, both under rest conditions and during exercise.
      MTWA was determined with the modified moving average method. HRV was expressed as
      root mean square of successive differences. RESULTS: Rest HRV at high altitude
      was significantly lower compared to rest HRV at sea level (36 +/- 5 vs 56 +/- 9
      ms, P = 0.003). HRV during exercise was significantly lower with respect to rest
      condition both in normoxia (46 +/- 7 vs 56 +/- 9 ms, P = 0.0001) and hypoxia (27
      +/- 4 vs 36 +/- 5 ms, P = 0.005). Moreover, HRV was significantly lower during
      exercise at high altitude compared to exercise at sea level (27 +/- 4 vs 46 +/- 7
      ms, P = 0.0002) and arrhythmias were more frequent during exercise in hypoxia.
      Nevertheless, MTWA was absent under rest conditions both at sea level and at high
      altitude and minimally evoked during exercise in both conditions (22 +/- 3 microV
      and 23 +/- 3 microV, respectively, P = 0.2). CONCLUSIONS: In spite of an enhanced
      sympathetic activity, MTWA testing during exercise at high altitude was negative
      in all participants. Healthy trained subjects during exercise under hypoxia seem
      to be at low risk for dangerous arrhythmias.

PMID- 18811809
TI  - Increased myocardial collagen turnover in patients with progressive cardiac
      conduction disease.
AB  - BACKGROUND: Histopathologically, progressive cardiac conduction disease (PCCD) is
      characterized by progressive fibrosis and sclerodegenerative changes in the
      proximal and distal conduction system of the heart. Therefore, we sought to
      determine the serum levels of myocardial collagen turnover markers, extracellular
      matrix components, transforming growth factor beta(1) (TGFbeta(1)), and bone
      morphogenic protein-7 (BMP-7) in this population. METHODS: Study population
      included 20 patients (6 M/14 F, mean age 76 +/- 8 years) with acquired, permanent
      2:1, or complete atrioventricular block and compared with age- and sex-matched,
      asymptomatic, healthy control subjects (n = 18, 6 M/12 F, mean age 75 +/- 7
      years). Serum myocardial collagen turnover markers:matrix metalloproteinases (MMP
      1, 2, 9), tissue inhibitor of matrix metalloproteinase (TIMP-1), amino-terminal
      propeptide of procollagen type I (PINP) and type III (PIIINP), carboxy-terminal
      telopeptide of collagen type I (CITP), and carboxy-terminal propeptide of
      procollagen type I (PICP), serum extracellular matrix components (laminin and
      fibronectin), TGFbeta(1), and BMP-7 levels were measured in both groups. RESULTS:
      Serum PICP (849 +/- 396 vs 631 +/- 294 ng/mL, P = 0.04), PIIINP (3.7 +/- 1.3 vs 3
      +/- 1 mug/L, P = 0.03), CITP (0.68 +/- 0.35 vs 0.48 +/- 0.25 ng/mL, P = 0.037),
      and plasma MMP-9 (58.8 +/- 56 vs 25.9 +/- 17.3 ng/mL, P = 0.006) levels were
      higher in patient population compared to control subjects. Serum MMP-1 (24.1 +/-
      20.5 vs 13.6 +/- 7.5 ng/mL, P = 0.045) and MMP-2 (1310 +/- 139 vs 1186 +/- 163
      ng/mL, P = 0.01) levels were higher in control subjects compared to patient
      population. There was no difference in serum TIMP-1, PINP, laminin, fibronectin,
      TGFbeta(1), and BMP-7 levels between two groups. CONCLUSION: Our findings
      demonstrate the presence of increased myocardial collagen turnover and active
      fibrotic process in patients with PCCD compared to control subjects.

PMID- 18811810
TI  - Performance of an autonomous telemonitoring system in children and young adults
      with congenital heart diseases.
AB  - BACKGROUND: Integrated telemonitoring systems controlling circulatory and
      electrical parameters in adults with an implanted pacemaker have shown to be
      advantageous during follow-up of this patient group. In children and young adults
      with a congenital heart disease (CHD), these systems have to cope with a
      diversity of varying arrhythmias and a broad range of intrinsic cardiac
      parameters. Additional problems arise from the patients' growth and anatomic
      anomalies. METHODS: Since 2005, eight young patients (age 4.1- 37 years, mean
      15.5 years) with a CHD received a pacemaker or implantable cardioverter
      defibrillator with an autonomous telemonitoring system at our clinic. The mean
      follow-up time was 395 days (range 106-834 days, 8.7 patient years). RESULTS: In
      seven of eight patients the system transmitted information, which led to
      beneficial modifications of the current antiarrhythmic therapy. In three patients
      the reported events were of a critical nature. One patient remained event-free
      for 192 days after implantation. During follow-up, 96% of the days were covered.
      The system also transferred additional information on the effectiveness of
      antiarrhythmic medication and the impact of physical activity. CONCLUSIONS: Young
      patients with an insufficient intrinsic heart rate or progressing arrhythmia, in
      addition to the conventional indications for pacemaker or defibrillator
      implantation, seem to profit to a high percentage from a telemetric surveillance
      system. The fully automated procedure of device interrogation and information
      transmission gives a daily overview on system function and specific arrhythmic
      events, especially in children who are unaware of any symptoms.

PMID- 18811811
TI  - The most common site of success and its predictors in radiofrequency catheter
      ablation of the slow atrioventricular nodal pathway in children.
AB  - BACKGROUND: Locating ablation targets on the slow pathway in children as one
      would in adults may not accommodate the dimensional changes of Koch's triangle
      that occur with heart growth. We investigated the most common site of success and
      the effect of a variety of variables on the outcome of slow pathway ablation in
      children. METHODS: A total of 116 patients (ages 4-16 years) with structurally
      normal hearts underwent radiofrequency ablation of either the antegrade or the
      retrograde slow pathway. Ablation sites were divided into eight regions (A1, A2,
      M1, M2, P1, P2, CS1, and CS2) at the septal tricuspid annulus. RESULTS: Ablation
      was successful in 112 (97%) children. The most common successful ablation sites
      were at the P1 region. The less the patient weighed, the more posteriorly the
      successful site was located (P = 0.023, OR 0.970, 95% CI 0.946-0.996), and the
      more likely the slow pathway was eliminated rather than modified: median weight
      was 46.7 kg (range, 14.5-94.3 kg) in the eliminated group and 56.5 kg (range, 20
      82.6 kg) in the modified group (P = 0.021, OR 1.039, 95% CI 1.006-1.073).
      CONCLUSIONS: The most common site of success for slow pathway ablation in
      children is at the P1 region of the tricuspid annulus. The successful sites in
      lighter children are more posteriorly located. Weight is also a predictor of
      whether the slow pathway is eliminated or only modified.

PMID- 18811812
TI  - Risk factors for atrioventricular tachycardia degenerating to atrial
      flutter/fibrillation in the young with Wolff-Parkinson-White.
AB  - BACKGROUND: Atrioventricular reciprocating tachycardia (AVRT) is common in
      patients (pts) with Wolff-Parkinson-White (WPW) syndrome but atrial
      flutter/fibrillation (AF) with rapid ventricular response (RVR) is rare. Although
      AF occurs in 18% of adult WPW pts, its incidence in children is unknown. We
      sought to determine risk factors for AVRT spontaneously degenerating to AF during
      electrophysiologic studies (EPS) in children with WPW. METHODS: This was a
      retrospective study of children with WPW referred for accessory pathway (AP)
      ablation without clinical AF. Standard electrophysiologic protocols were
      performed to induce AVRT. To determine if AF degeneration was associated with
      patient characteristics, 2-sample t-tests, Chi-square, and Fisher's exact were
      used. RESULTS: There were 53 (31 males) WPW pts studied. During EPS, AVRT
      degenerated to AF in 27/53 (51%). RVR was seen in 18/27 (67%) patients. The
      ventricular cycle length (CL) during AF was shorter with RVR (211 + 24 ms) than
      without (313 + 65 ms) (P = 0.01). AF occurred more commonly among patients with
      right anterior AP (P = 0.05). Patient gender, age, height, weight, body surface
      area, persistence of preexcitation on exercise testing, baseline CL, AVRT
      conduction, and AP number were not significant AF determinants. The AVRT CL was
      significantly shorter in patients with (265.2 + 41.5 ms) versus those without
      (308 + 59 ms) AF (P = 0.01). Preliminary data suggest that AP location may be
      related to patient ethnicity. CONCLUSION: AF with RVR occurred following AVRT
      induction during EPS in 34% of our WPW patients, typically associated with right
      sided AP locations. Time intervals for RVR to degenerate into ventricular
      fibrillation and lead to SCD are yet to be determined.

PMID- 18811813
TI  - Remote magnetic versus manual catheter navigation for ablation of
      supraventricular tachycardias: a randomized, multicenter trial.
AB  - INTRODUCTION: The potential benefits of remote robotic navigation for catheter
      ablation procedures have not been demonstrated in controlled clinical trials. The
      purpose of this study was to compare remote magnetic catheter navigation to
      manual navigation for the ablation of common supraventricular arrhythmias.
      METHODS AND RESULTS: Patients with supraventricular arrhythmias due to
      atrioventricular (AV) nodal reentry, accessory pathways, or undergoing AV
      junctional ablation for complete heart block were randomized in a 3:1 ratio
      between magnetic (Niobe system and Helios II catheter, Stereotaxis, Inc., St.
      Louis, MO) and manual navigation for radiofrequency ablation at 13 centers. The
      primary endpoint of the study was total fluoroscopic time. Fifty-six patients
      were randomized to magnetic navigation and 15 to manual navigation. AV nodal
      reentry was the most common arrhythmia in both groups. Total fluoroscopy time was
      reduced in the magnetic navigation group (median 17.8 minutes, interquartile (IQ)
      range 9.9,27.8 minutes) compared to manual navigation (27.1, IQ 19.0,48.0, P <
      0.05). The acute success rates (91% for magnetic and 87% for manual navigation, P
      > 0.05) did not differ between groups. The number of lesions delivered was less
      for magnetic navigation (6, IQ 4,9 vs 10, IQ 7, 26, P < 0.05). Total procedure
      time (median 151, IQ 111, 221 minutes magnetic and 151, IQ 110, 221 minutes
      manual) and complication rates (5.4% patients magnetic and 6.7% patients manual)
      were similar between the groups (both P > 0.05). CONCLUSIONS: Remote magnetic
      catheter navigation reduces fluoroscopic time and radiofrequency lesion
      deliveries for the ablation of common supraventricular arrhythmias compared to
      manual catheter navigation.

PMID- 18811814
TI  - Focal and linear endocardial and epicardial catheter-based cryoablation of normal
      and infarcted ventricular tissue.
AB  - BACKGROUND: This study of a chronic porcine postinfarction model examined whether
      linear epicardial cryoablation was capable of creating large, homogenous lesions
      in regions of the myocardium including scarred ventricle. Endocardial and
      epicardial focal cryolesions were also compared to determine if there were
      significant differences in lesion characteristics. METHODS: Eighty focal
      endocardial and 28 focal epicardial cryoapplications were delivered to eight
      normal caprine and four normal porcine ventricular myocardium, and 21 linear
      cryolesions were applied along the border of infarcted epicardial tissue in a
      chronic porcine infarct model in six swines. RESULTS: Focal endocardial
      cryolesions in normal animals measured 9.7+/-0.4 mm (length) by 7.3+/-1.4 mm
      (width) by 4.8+/-0.2 mm (depth), while epicardial lesions measured 10.2+/-1.4 mm
      (length) by 7.7+/-2 mm (width) by 4.6+/-0.9 mm (depth); P > 0.05. Linear
      epicardial cryolesions in the chronic porcine infarct model measured 36.5+/-7.8
      mm (length) by 8.2+/-1.3 mm (width) by 6.0+/-1.2 mm (depth). The mean depth of
      linear cryolesions applied to the border of the infarct scar was 7+/-0.7 mm, as
      measured by magnetic resonance imaging. CONCLUSIONS: Cryoablation can create deep
      lesions when delivered to the ventricular epicardium. Endocardial and epicardial
      cryolesions created by a focal cryoablation catheter are similar in size and
      depth. The ability to rapidly create deep linear cryolesions may prove to be
      beneficial in substrate-based catheter ablation of ventricular arrhythmias.

PMID- 18811815
TI  - Supraventricular tachycardia coexisting with apparent Mobitz I and II
      atrioventricular block: a single mechanism?

PMID- 18811816
TI  - Conduction barriers of atrial flutter: relation to the anatomy.
AB  - Atrial flutter (AFL) is a common arrhythmia in clinical practice. Several
      experimental models such as tricuspid ring model, tricuspid regurgitation model,
      and atrial crush injury model have provided important information about the role
      of conduction barriers in the reentrant circuit. Human typical AFL uses the
      tricuspid annulus as the anterior barrier, and uses the crista terminalis,
      Eustachian ridge, and sometimes sinus venosa as the posterior boundary. Rate
      dependent conduction block was found in the crista terminalis and sinus venosa.
      Some barriers such as the crista terminalis and Eustachian ridge are not intact.
      The conduction gap in the barrier can produce another kind of arrhythmia.
      Understanding the barriers of AFL is necessary for successful radiofrequency
      ablation.

PMID- 18811817
TI  - A river of light.

PMID- 18811818
TI  - Electromagnetic interference in an implantable loop recorder caused by a portable
      digital media player.
AB  - The implantable loop recorder has been shown to be a cost-effective tool for
      diagnosis of intermittent cardiovascular symptoms such as syncope and
      palpitations. Electromagnetic interference in these recorders may be caused by
      commonly encountered electronic devices such as antitheft electronic surveillance
      systems and magnetic resonance imaging cameras. In this report, we describe
      interference in two patients with implantable loop recorders from a portable
      digital media player.

PMID- 18811819
TI  - Coexistent right- and left-sided slow pathways participating in distinct AV nodal
      reentrant tachycardias.
AB  - We report a patient with two distinct atrioventricular (AV) nodal slow pathways,
      participating in two different AV nodal reentrant tachycardias--one eliminated
      from the right, the other only after ablation on the left side of the posterior
      septum. The case provides support for the concept of the posterior AV nodal
      extensions--a biatrial structure in most hearts--representing the anatomic basis
      of slow pathway conduction.

PMID- 18811820
TI  - Biventricular ICD implantation using the iliofemoral approach: providing CRT to
      patients with occluded superior venous access.
AB  - A 32-year-old woman with a history of nonischemic dilated cardiomyopathy, left
      bundle branch block, left ventricular ejection fraction of 0.15, and New York
      Heart Association Class III congestive heart failure, despite optimal medical
      treatment, was referred for cardiac resynchronization therapy with implantation
      of an implantable cardioverter defibrillator. The patient had prior chemotherapy
      for non-Hodgkin's lymphoma and was shown to have chronic total occlusion of the
      superior vena cava (SVC) by magnetic resonance imaging. Cardiac resynchronization
      was accomplished with an iliofemoral approach without complications resulting in
      marked clinical improvement. We conclude that the iliofemoral approach allows
      transvenous implantation of cardiac resynchronization therapy in patients with
      superior vena cava occlusion.

PMID- 18811821
TI  - Automatic magnetic-guided electroanatomical mapping and remote-controlled
      ablation of atypical and typical atrial flutter.
AB  - Two patients with inconclusive surface electrocardiogram patterns underwent
      nonfluoroscopy automatic mapping and remote-controlled ablation of nonisthmus and
      isthmus-dependent right atrial flutter. METHODS AND RESULTS: A 0.08 magnetic
      vector force and a motor drive enable a complex steering of a new 8-mm magnet tip
      electrode. The navigation system performs atrial electroanatomical mapping fully
      automatically. Total procedural fluoroscopy time for ablation of nonisthmus
      related atypical and isthmus-dependent flutter was 8.5 and 3.2 minutes,
      respectively. CONCLUSION: Automatic electroanatomical mapping offers a promising
      option to effectively guide the remote-controlled ablation of atrial reentry
      tachycardias and to reduce fluoroscopy time.

PMID- 18811822
TI  - Focal AF-ablation after pulmonary vein isolation in a patient with hypertrophic
      cardiomyopathy using cryothermal energy.
AB  - A 42-year-old man, with a history of hypertrophic cardiomyopathy (HCM), an
      electrocardiogram pattern of ventricular preexcitation typical for mutations in
      the PRKAG2 gene, and highly symptomatic paroxysmal drug-resistant atrial
      fibrillation (AF), underwent successful circumferential isolation of his
      pulmonary veins using a 28-mm double lumen cryoballoon. Because AF was still
      inducible with programmed stimulation, fractionated signals were targeted in the
      left atrium with a conventional cryocatheter. Ablation of an endocardial focus
      with fractionated potentials at the base of the left appendage terminated the
      episode and rendered AF noninducible. No recurrence of AF was observed during a
      10-month follow-up period.

PMID- 18811823
TI  - What is it--rare, nonreentrant, and supraventricular?

PMID- 18811825
TI  - Is the T-Wave amplitude an independent (to the inherent arrhythmogenicity)
      determinant of the magnitude of T-wave alternans?

PMID- 18811827
TI  - Paracetamol (Acetaminophen): mechanisms of action.
AB  - Paracetamol has a central analgesic effect that is mediated through activation of
      descending serotonergic pathways. Debate exists about its primary site of action,
      which may be inhibition of prostaglandin (PG) synthesis or through an active
      metabolite influencing cannabinoid receptors. Prostaglandin H(2) synthetase
      (PGHS) is the enzyme responsible for metabolism of arachidonic acid to the
      unstable PGH(2). The two major forms of this enzyme are the constitutive PGHS-1
      and the inducible PGHS-2. PGHS comprises of two sites: a cyclooxygenase (COX)
      site and a peroxidase (POX) site. The conversion of arachidonic acid to PGG(2) is
      dependent on a tyrosine-385 radical at the COX site. Formation of a ferryl
      protoporphyrin IX radical cation from the reducing agent Fe(3+) at the POX site
      is essential for conversion of tyrosine-385 to its radical form. Paracetamol acts
      as a reducing cosubstrate on the POX site and lessens availability of the ferryl
      protoporphyrin IX radical cation. This effect can be reduced in the presence of
      hydroperoxide-generating lipoxygenase enzymes within the cell (peroxide tone) or
      by swamping the POX site with substrate such as PGG(2). Peroxide tone and
      swamping explain lack of peripheral analgesic effect, platelet effect, and anti
      inflammatory effect by paracetamol. Alternatively, paracetamol effects may be
      mediated by an active metabolite (p-aminophenol). p-Aminophenol is conjugated
      with arachidonic acid by fatty acid amide hydrolase to form AM404. AM404 exerts
      effect through cannabinoid receptors. It may also work through PGHS, particularly
      in areas of the brain with high concentrations of fatty acid amide hydrolase.

PMID- 18811828
TI  - Alteration of anion gap and strong ion difference caused by hydroxyethyl starch
      6% (130/0.42) and gelatin 4% in children.
AB  - BACKGROUND: Synthetic colloid administration is a common practice for preventing
      perioperative hypovolemia and consecutive circulatory failure in children. This
      prospective, randomized study was conducted to investigate the effects of two
      different unbalanced synthetic colloid solutions on acid-base equilibrium in
      children. METHODS: Fifty pediatric patients (aged 0-12 years) scheduled for major
      pediatric surgery were randomized to receive either 10 ml x kg(-1) of 6%
      hydroxyethyl starch solution 130/0.42 (HES) or 4% modified fluid gelatin (GEL) to
      maintain adequate systemic hemodynamics. Before and after colloid administration,
      a blood sample was collected to analyze hemoglobin, hematocrit, electrolytes, and
      acid-base parameters. The anion gap and the strong ion difference (SID) were
      calculated using standard formulas. RESULTS: Both HES and GEL administration
      caused a significant increase in plasma chloride concentration (P < 0.01) and an
      accompanying decrease in SID (P < 0.01). In the HES group, the anion gap
      decreased significantly (P < 0.01) whereas the anion gap remained stable in the
      GEL group. In both groups, initial actual base excess and pH did not change
      significantly after colloid administration. CONCLUSIONS: Moderate intraoperative
      plasma replacement with unbalanced synthetic colloids HES and GEL leads to a
      decrease in SID and, in the case of HES, to a significant decrease in the anion
      gap in children. These alterations may result in a possible misinterpretation
      when the anion gap and SID are used for differential diagnosis of metabolic
      disturbances during major pediatric surgery.

PMID- 18811829
TI  - Safe general anesthesia in a hyperkalemic infant.
AB  - A 10-day-old boy treated in the intensive care unit and operating room due to
      hyperkalemia and renal failure. After admission to the intensive care unit and
      treatment for hyperkalemia, the patient required insertion of dialysis catheter
      in the operating room. Treatment for hyperkalemia continued while the patient was
      under general anesthesia. The operation was carried out successfully and cardiac
      signs and symptoms of hyperkalemia did not occur despite of potassium blood
      levels of 8.1 mEq x l(-1). General anesthesia could be safe in hyperkalemic
      patients as long as the treatment for hyperkalemia is initiated before and during
      the surgery and hyperkalemia inducing agents are avoided.

PMID- 18811830
TI  - Laryngospasm.

PMID- 18811831
TI  - Management of laryngospasm - our concerns and suggestions.

PMID- 18811832
TI  - Paradoxical vocal cord motion - another cause to differentiate from laryngospasm.

PMID- 18811833
TI  - Rapid sequence induction in children - it's not a matter of time! Or is it?

PMID- 18811834
TI  - Airway management of a neonate with a rare congenital palatoglossal synechiae.

PMID- 18811836
TI  - Increasing the margin of safety during intubation through the laryngeal mask (a
      reply to Drs Jagannathan and Sohn).

PMID- 18811835
TI  - Tracheal agenesis: perioperative management of one stage correction.

PMID- 18811837
TI  - Unrecognized obstructive sleep apnea in children: caught on the wrong foot and
      lessons learnt!!!

PMID- 18811838
TI  - Limitations of self-made jet devices.

PMID- 18811839
TI  - Laryngeal web in an infant with ventricular septal defect: a case of misdiagnosed
      congestive heart failure.

PMID- 18811840
TI  - Airway management in a patient with division of tongue flap.

PMID- 18811841
TI  - Safe oral to nasal tube exchange using the fiberoptic bronchoscope in management
      of pediatric difficult airway.

PMID- 18811842
TI  - Difficult intubation in a small for gestational age newborn by bonfils
      fiberscope.

PMID- 18811843
TI  - Emergency airway management of an extremely low-birth-weight infant with
      subglottic stenosis.

PMID- 18811844
TI  - Pyloromyotomy in an infant with hypoplastic left heart syndrome status-post
      hybrid procedure: not just another case?

PMID- 18811845
TI  - Anesthetic management of a child with congenital heart disease and pulmonary
      artery banding for ophthalmic surgery.

PMID- 18811846
TI  - Anesthetic management of adenotonsillectomy in a child with bidirectional
      superior cavapulmonary shunt.

PMID- 18811847
TI  - Acute development of superior vena cava syndrome after pediatric cardiac surgery.

PMID- 18811848
TI  - Sinus venosus atrial septal defect closure in an achondroplastic dwarf:
      anesthetic and cardiopulmonary bypass management issues.

PMID- 18811849
TI  - Respiratory failure in a former preterm infant following high spinal anesthesia
      with bupivacaine and clonidine.

PMID- 18811850
TI  - Anesthetic management of a child with acrocallosal syndrome.

PMID- 18811851
TI  - Iatrogenic severe hyperglycemia in a child undergoing adenoidectomy and
      tonsillectomy.

PMID- 18811852
TI  - Successful resuscitation of unexpected neonatal hemorrhagic shock due to massive
      feto-maternal hemorrhage.

PMID- 18811853
TI  - Duchenne muscular dystrophy: Which is the best anesthetic agent?

PMID- 18811854
TI  - A combination of ketamine and dexmedetomidine sedation with caudal anesthesia
      during incarcerated inguinal hernia repair in three high-risk infants.

PMID- 18811855
TI  - Dexmedetomidine and ketamine for large anterior mediastinal mass biopsy.

PMID- 18811856
TI  - Parents and patients' compliance to revised preoperative fasting guidelines in
      Benin, Nigeria.

PMID- 18811862
TI  - Role of photodynamic therapy in psoriasis: a brief review.
AB  - BACKGROUND AND PURPOSE: Photodynamic therapy (PDT) is a light treatment modality
      which involves either systemic or local application of a photosensitizing
      compound, which preferentially deposits in the target cells, and is then followed
      by selective illumination of the lesion with visible light. The purpose of this
      study was to review the literature to examine the success, side effects, and
      different protocols used thus far to treat psoriasis using PDT. METHODS: A
      thorough review of the literature was performed and analyzed. RESULTS AND
      CONCLUSIONS: After a thorough review of the literature, PDT remains a potential
      treatment for psoriasis. Clinical improvement has been observed in most studies.
      The major limiting factor seen in many of the studies was the side effect of pain
      and burning sensations associated with PDT. This highlights the need for other
      photosensitizers with better tolerability profiles.

PMID- 18811863
TI  - Evaluation of 308-nm monochromatic excimer light in the treatment of psoriasis
      vulgaris and palmoplantar psoriasis.
AB  - BACKGROUND: The purpose of this study is to evaluate the efficacy and safety of
      308-nm monochromatic excimer light (MEL) in the treatment of psoriasis vulgaris
      and palmoplantar psoriasis. METHODS: Thirty-five patients with psoriasis vulgaris
      and 15 patients with palmoplantar psoriasis were recruited for this study. Thirty
      patients with psoriasis vulgaris completed a total of 16 treatments with 308-nm
      MEL twice a week, and 15 patients palmoplantar psoriasis completed 25 treatments
      administered once weekly. The clinical response to therapy and adverse effects
      were recorded. RESULTS: Patients with psoriasis vulgaris (n=30) showed a 74.6%
      improvement in the mean psoriasis area and severity index score after a total of
      16 MEL treatments (2 x /week) with 36.7% of the patients (n=11) achieving
      clearance. Patients with palmoplantar psoriasis (n=15) showed a 52.5% improvement
      in the mean severity index score after a total of 25 MEL treatments (1 x /week)
      with only one patient (6.7%) achieving clearance. The MEL therapy was well
      tolerated with a low incidence of side effects, which included pruritus, erythema
      and blister formation. CONCLUSION: The 308-nm MEL can be utilized as an effective
      and safe treatment modality for patients with mild-to-moderate psoriasis vulgaris
      and palmoplantar psoriasis.

PMID- 18811864
TI  - 5-aminolaevulinic acid and photodynamic therapy reduce HSV-1 replication in HaCat
      cells through an apoptosis-independent mechanism.
AB  - BACKGROUND: Photodynamic therapy (PDT) involves the use of a photosensitizing
      agent, which may require metabolic synthesis (i.e. a prodrug), followed by light
      activation. Numerous studies have advanced PDT as a means for treating bacteria,
      fungi and viruses. In this study, the photoinactivation of Herpes simplex virus
      type 1 (HSV-1) in human keratinocytes using 5-aminolaevulinic acid (5-ALA) was
      investigated. METHODS: HaCat cells were infected with HSV-1 and treated with 5
      ALA to verify its antiviral effect during the stages of adsorption and
      penetration to host cells. Immunoblot analysis was used to estimate the effect of
      ALA-PDT on the production of viral proteins glycoprotein D (gD), infected cell
      proteins (ICP) 27 and virion protein (VP) 16. We also investigated whether the
      effect of ALA-PDT was associated with a cellular apoptotic mechanism through DNA
      fragmentation and the study of p53, PARP and caspase-3 protein expression.
      RESULTS: While the treatment of ALA-PDT after the viral adsorption period reduced
      HSV-1 replication by about 70%, it did not act on the virus in the first phase of
      infection. The viral proteins' expressions were reduced by ALA-PDT treatments.
      There was no evidence of ALA-PDT-induced apoptosis. CONCLUSION: Our data suggest
      that the target of photoinactivation appears to be viral replication and not a
      cellular response.

PMID- 18811865
TI  - Non-invasive diagnostic evaluation of phototherapeutic effects of red light
      phototherapy of acne vulgaris.
AB  - BACKGROUND: During the past few years, various phototherapeutic protocols with
      full-spectrum visible light or selected wavebands have been investigated in the
      treatment of acne vulgaris with variable results. METHODS: Fifteen women
      suffering from moderate acne vulgaris of the face were exposed to 20 J/cm(2) of
      broad-band red (lambda: 600-750 nm) light twice weekly for 4 weeks. In addition,
      with the aim to improve the present knowledge of the mechanisms of action of
      phototherapy, we measured skin sebum, pH, hydration and trans-epidermal water
      loss (TEWL). Lesions of the trunk were not irradiated and served as controls.
      RESULTS: A significant improvement of acne lesions and a significant decrease of
      skin sebum excretion and TEWL of the face were registered at the end of the
      therapy and at the 3-month follow-up visit. The results could be related to a
      reduced follicular colonization of Propionibacterium acnes, in that it was
      lethally damaged by photoactivated endogenous porphyrins. CONCLUSION: The present
      findings seem to indicate that red light phototherapy may represent an effective,
      well-tolerated, safe, simple and inexpensive treatment option for moderate acne
      vulgaris.

PMID- 18811866
TI  - Evaluation of sunscreen products using a reconstructed skin model exposed to
      simulated daily ultraviolet radiation: relevance of filtration profile and SPF
      value for daily photoprotection.
AB  - BACKGROUND: The recent definition of a standard daily ultraviolet radiation
      (DUVR) has allowed us to reproduce non-zenithal sun exposure conditions. Exposure
      to simulated DUVR induces biological damage in human skin, suggesting the need
      for an appropriate photoprotection. METHODS: Sunscreen products were evaluated
      using human reconstructed skin in vitro. Two commercial sunscreens (A and B)
      having similar sun (burn) protection factor (SPF) values (approximately 15) but
      different profiles of transmission over the UVA range were tested on skin models
      exposed to increasing doses of DUVR. Another pair of sunscreens was also tested.
      One (product C) had an SPF approximately 18 with a well-balanced UVB-UVA profile
      and the other (product D) an SPF of approximately 27 with low UVA absorption.
      Biological parameters were assessed by (i) histology, (ii) vimentin
      immunostaining for dermal fibroblasts, and (iii) analysis of matrix
      metalloprotease (MMP)-1 secretion. RESULTS: Products A and C gave better
      protection from DUVR with regard to fibroblast alterations and MMP-1 release
      compared with products B and D, respectively. CONCLUSION: To ensure an efficient
      daily photoprotection from DUVR, the filtration profile of the product should be
      well balanced with a sufficient level of UVA absorption. With regard to end
      points evaluated in this study, our data suggest that a higher SPF value does not
      compensate for low UVA filtration.

PMID- 18811867
TI  - Different narrowband UVB dosage regimens in dark skinned psoriatics: a
      preliminary study.
AB  - BACKGROUND: Psoriasis is a common and relapsing disease, which is both physically
      and psychologically disabling. Narrowband UVB (NB-UVB) is used in fair-skinned
      population in suberythemogenic doses with good results; however, in the darker
      skin population (skin types III, IV, V) erythemogenic doses have not been
      thoroughly investigated. AIM: A left-right bilateral comparative trial was
      carried out to compare the suberythemogenic dose of NB-UVB vs. erythemogenic dose
      in the treatment of dark-skinned psoriatic patients. PATIENTS AND METHODS: The
      study was conducted on 20 patients with chronic plaque psoriasis. The left side
      was treated with the dose causing minimal erythema [100% of minimal erythema dose
      (MED)] while the right side received 70% of this MED (suberythemogenic side).
      RESULTS: Our results revealed no statistically significant difference in PASI
      final and in the percentage of reduction of PASI score between both sides as well
      as the total number of sessions (P-value>0.05), while the total cumulative UVB
      dose on the suberythemogenic side was significantly lower (P-value<0.001).
      CONCLUSION: Our study recommends reducing the dose regimen of NB-UVB and
      consequently the cumulative UVB dose by using the suberythemogenic dosing
      schedule even in dark skin population.

PMID- 18811868
TI  - Photoprotective behaviour and sunscreen use: impact on vitamin D levels in
      cutaneous lupus erythematosus.
AB  - BACKGROUND: Sun exposure of the skin, independent of dietary sources, may provide
      sufficient vitamin D in healthy individuals. A recent study of patients with
      cutaneous lupus erythematosus concluded that over 70% of them restrict their sun
      exposure. METHODS: We recruited 52 patients with biopsy-proven cutaneous lupus
      erythematosus to establish whether they are deficient in 25-hydroxyvitamin D
      [25(OH)D]. We measured their serum 25(OH)D levels during summer months,
      investigated the effects of several variables on 25(OH)D levels and assessed the
      role of vitamin D supplementation. RESULTS: An overall mean 25(OH)D level of
      63.03 (+/-23.3) nmol/l was obtained. Significantly low values (<25 nmol/l) were
      recorded in two (3.8%) patients and concentrations below 75 nmol/l were found in
      34 (65.4%) patients. 25(OH)D levels were significantly lower among sun avoiders
      and daily sunscreen users, while significantly higher values were found among
      those who took cholecalciferol (vitamin D3) supplements. Low values were recorded
      among those with renal disease despite supplementation with vitamin D3 in some
      cases. CONCLUSIONS: We suggest that patients with cutaneous lupus erythematous
      have suboptimal 25(OH)D levels, which are significantly raised by the addition of
      at least 400 IU/day of cholecalciferol. We recommend supplementation with an
      active vitamin D analogue in collaboration with a consultant nephrologist, for
      the subgroup of patients with renal disease.

PMID- 18811869
TI  - Local effects of TL01 phototherapy in psoriasis.
AB  - The mechanisms whereby narrowband ultraviolet B (UVB) (311-313 nm, TL01)
      phototherapy are effective in psoriasis may differ from those occurring in
      broadband UVB phototherapy. In the present study, changes in epidermal cells as a
      result of TL01 therapy were assessed in the skin of patients with psoriasis. The
      non-lesional skin of five subjects with plaque psoriasis was biopsied before and
      after a series of 12 whole-body TL01 treatments. Following appropriate staining
      of skin sections, the numbers of p53-positive keratinocytes, sunburn cells and
      Langerhans cells in the epidermis were counted. TL01 therapy induced a threefold
      increase in the number of p53-positive epidermal cells, a 12-fold increase in
      sunburn cells and a twofold decrease in Langerhans cells. The increase in
      epidermal p53 expression and apoptosis of keratinocytes together with the
      depletion of Langerhans cells in the non-lesional skin of psoriasis patients are
      likely to contribute to the effectiveness of TL01 phototherapy.

PMID- 18811870
TI  - Dapsone-induced photosensitivity: a rare clinical presentation.
AB  - Dapsone is an efficient anti-inflammatory and antimycobacterial agent. It is one
      of the main constituents of multidrug therapy (MDT). It acts by interference with
      folate metabolism. Dapsone-induced photosensitivity is a rare, non-dose-related
      adverse effect of the sulfone and can occur in patients with inflammatory skin
      disorders treated with dapsone. So far, only 12 cases seem to have been reported
      in the literature. We report a case of dapsone-induced photosensitivity in an
      Indian patient with leprosy.

PMID- 18811871
TI  - Actinic prurigo.
AB  - Actinic Prurigo (AP), an uncommon idiopathic photodermatosis, presents a distinct
      clinical picture and can be severely debilitating. The clinical features,
      investigation and treatment of AP are reviewed. We report the experience of an
      Australian photobiology unit with this condition.

PMID- 18811875
TI  - Regulation of consumer products: the bizarre case of strawberry jam and
      cigarettes.

PMID- 18811876
TI  - Phosphoinositide 3-kinase delta inhibitor as a novel therapeutic agent in asthma.
AB  - Multiple signal transduction pathways are involved in airway inflammation with
      one of the key signalling pathways being phosphoinositide 3-kinase (PI3K).
      Numerous components of the PI3K pathway play an important role in the expression
      and activation of inflammatory mediators, inflammatory cell recruitment, immune
      cell function, airway remodelling and corticosteroid insensitivity in asthma.
      More recently studies exploring the specific roles of different PI3K catalytic
      subunit isoforms in asthma have been initiated. Several of these have highlighted
      the importance of p110delta isoform as a novel target for therapeutic
      intervention in asthma. In this review the biological role of PI3Ks, especially
      PI3Kdelta, are highlighted and the therapeutic potential of selective PI3Kdelta
      inhibitor in asthma discussed.

PMID- 18811877
TI  - Effects of Th2 pulmonary inflammation in mice with bleomycin-induced pulmonary
      fibrosis.
AB  - BACKGROUND AND OBJECTIVE: Leucocytes, especially lymphocytes and neutrophils, as
      well as alveolar macrophages, that infiltrate into the lung are involved in the
      development of pulmonary fibrosis. However, the role of T helper (Th)2-type
      inflammation, mediated by Th2 cells and eosinophils, in fibrosis remains unknown.
      Transgenic mice deficient in the transcriptional repressor, Bcl6, display an
      attenuation of Th2 cytokine production. We studied the effects of Th2-type
      pulmonary inflammation on bleomycin-induced pulmonary fibrosis using Bcl6
      transgenic mice. METHODS: Bleomycin was administered to ovalbumin (OVA)
      sensitized Bcl6 transgenic and wild-type mice by intratracheal instillation
      during sequential OVA antigen challenge. Concentrations of transforming growth
      factor-beta1 in the BAL fluid were measured 2 weeks after bleomycin
      administration. At the same time lung tissue was examined histopathologically,
      and homogenized to assess collagen levels and Th1/Th2 cytokine mRNA expression.
      RESULTS: Although OVA-sensitized, bleomycin-treated Bcl6 transgenic mice had
      markedly lower numbers of eosinophils in both BAL and lung tissue compared with
      OVA-sensitized, bleomycin-treated wild-type mice, the development of pulmonary
      fibrosis in response to bleomycin was similar in Bcl6 transgenic mice and wild
      type mice. CONCLUSION: These results suggest that Th2-dominant inflammation in
      the lung is not essential for the development of bleomycin-induced pulmonary
      fibrosis.

PMID- 18811878
TI  - Bronchodilator reversibility, airway eosinophilia and anti-inflammatory effects
      of inhaled fluticasone in COPD are not related.
AB  - BACKGROUND AND OBJECTIVE: Bronchodilator reversibility (BDR) is common in smoking
      related COPD, but the airway pathology underlying this has not been described. In
      particular, it is not known whether BDR is associated with underlying airway
      eosinophilia and whether BDR is predictive of a better response to inhaled
      corticosteroid (ICS) treatment. METHODS: A double-blind, placebo-controlled,
      randomized 2:1 study of fluticasone propionate (FP), 500 microg twice daily
      versus placebo over 6 months was performed in subjects with mild to moderate
      COPD. Subjects with a clinical history of asthma were excluded, but not on BDR
      criteria alone. Induced sputum, BAL and endobronchial biopsies (EBB) were
      performed in 36 subjects at baseline, and 30 of these provided a second full set
      of samples (FP, n = 19; placebo, n = 11). RESULTS: Baseline BDR was not related
      to airway eosinophilia and did not predict response to ICS. Post-bronchodilator
      FEV(1) increased in the FP group compared with the placebo group (P = 0.05), and
      there were within-treatment group reductions in total symptom scores with FP (P <
      0.05). Compared with placebo, FP reduced macrophage numbers but increased
      neutrophil numbers in EBB (P = 0.01 and P = 0.003, respectively). BAL neutrophil
      and epithelial cell numbers were also reduced with FP (P = 0.03 for both). There
      were within-treatment group reductions in the numbers of EBB mast cells and
      CD8+ve lymphocytes with FP (P = 0.007). CONCLUSIONS: BDR was not related to any
      particular inflammatory phenotype or any clinical or anti-inflammatory response
      to ICS in these subjects with mild to moderate COPD.

PMID- 18811879
TI  - Acylated ghrelin level in patients with OSA before and after nasal CPAP
      treatment.
AB  - BACKGROUND AND OBJECTIVE: Patients with newly diagnosed OSA have been reported to
      have recent weight gain prior to diagnosis. Ghrelin stimulates food intake and
      increases weight gain. Plasma ghrelin is decreased in obese and increased in lean
      individuals. Of the two circulating forms of ghrelin, acylated and unacylated,
      the former is thought to be essential for the biological activity of ghrelin.
      METHODS: The plasma levels of the two forms of ghrelin were measured in 21 OSA
      patients (with a mean of 46.2 sleep-disordered events/h) before and after 1 month
      of nasal CPAP (nCPAP) treatment, and were compared with those in 14 untreated OSA
      patients and 13 individuals without OSA. RESULTS: The BMI was significantly
      higher in the 21 OSA patients than in the non-OSA group as were the baseline
      acylated (11.4 +/- 5.86 vs 7.19 +/- 3.80 fmol/mL, P = 0.03) and unacylated (84.2
      +/- 50.6 vs 48.3 +/- 23.2 fmol/mL, P = 0.02) ghrelin levels. The total ghrelin
      level was positively correlated with the number of sleep-disordered breathings (P
      = 0.002). After 1 month of nCPAP treatment, the acylated ghrelin level
      significantly decreased (P = 0.02) while the unacylated ghrelin level did not (P
      = 0.09). CONCLUSIONS: Treatment of OSA may play an important role in the
      management of obesity in these patients by reducing the acylated ghrelin level.

PMID- 18811880
TI  - Radiological diagnosis of small pulmonary nodules detected on low-dose screening
      computed tomography.
AB  - BACKGROUND AND OBJECTIVE: Early detection and treatment of small malignant
      pulmonary lesions can improve survival; however, screening by CT detects many
      false positives. This study retrospectively evaluated a protocol for the
      diagnostic work-up of nodules detected by low-dose CT (LDCT) that are < or = 10
      mm in diameter. METHODS: A health screening programme included LDCT. Lesions
      detected were allocated to one of four categories: negative, semi-negative,
      positive and semi-positive. Positive and semi-positive categories included non
      calcified nodules without a polygonal shape, and these patients had an initial
      diagnostic HRCT and were then followed up using high-resolution CT (HRCT) at
      intervals determined by the characteristics of the lesion on screening LDCT and
      the initial diagnostic HRCT. RESULTS: There were 275 nodules detected on
      screening LDCT; 84 patients had lesions classified as positive and 99 as semi
      positive. Thirteen nodules detected on screening LDCT were only determined to be
      polygonal and benign following the diagnostic HRCT. The sensitivity and
      specificity of the screening CT, when compared with diagnostic HRCT, for
      determining if nodules should be classified as positive were 100% and 97%. The
      sensitivity and specificity of the initial diagnostic HRCT for being able to
      predict lung cancer were 87.5% and 91.7% respectively. CONCLUSIONS: Following the
      detection of a pulmonary lesion on screening LDCT, a diagnostic HRCT is necessary
      to determine the timing of follow-up HRCT. Diagnostic HRCT is needed to
      rationalize the screening for lung cancer to reduce the frequency of unnecessary
      follow-up scans.

PMID- 18811881
TI  - Underlying aetiology of pulmonary hypertension in 191 patients: a single centre
      experience.
AB  - BACKGROUND AND OBJECTIVE: The aim of this study was to describe the prevalence
      and annual incidence, as well as the aetiology of pulmonary hypertension (PHT) in
      a PHT clinic, so as to assist in future assessments of the economic burden of
      PHT. METHODS: The medical records for all new cases of PHT, defined as systolic
      pulmonary artery pressure >45 mm Hg as measured by Doppler echocardiography, or
      as mean pulmonary artery pressure >25 mm Hg measured at cardiac catheterization,
      between January 1998 and December 2005, were reviewed. The aetiology of the PHT
      was recorded and separate mean annual incidences were calculated. RESULTS: The
      study population included 191 patients ranging in age from 16 to 90 years.
      Respiratory disorders were the leading aetiology for PHT, accounting for 31% of
      cases, followed by collagen vascular diseases (19%), idiopathic (12%),
      haemodialysis (13%), chronic thromboembolism (8%), haematological diseases (7%),
      liver cirrhosis (6%) and hypoventilation syndrome (4%). The mean annual incidence
      of PHT was 15.9 new cases per million citizens per year, with a mean annual
      incidence due to respiratory disease of 4.82 (COPD, 3.83), collagen vascular
      disease 3.08, haemodialysis 2.08, idiopathic 1.92, chronic thromboembolism 1.33,
      haematological disease 1.17, liver disease 0.92 and hypoventilation syndrome
      0.58. The mean annual incidence of PAH and chronic thromboembolic PHT that fitted
      the guidelines for therapy was 8.58 cases per year per million citizens.
      CONCLUSION: The current data may help in estimating the economic burden of PHT.

PMID- 18811882
TI  - Association between polymorphisms of microsomal epoxide hydrolase and COPD:
      results from meta-analyses.
AB  - BACKGROUND AND OBJECTIVE: COPD is a complex polygenic disease in which gene
      environment interactions are very important. The gene encoding microsomal epoxide
      hydrolase (EPHX1) is one of several candidate loci for COPD pathogenesis and is
      highly polymorphic. Based chi on the polymorphisms of EPHX1 gene
      (tyrosine/histidine 113, histidine/arginine 139), the population can be
      classified into four groups of putative EPHX1 phenotypes (fast, normal, slow and
      very slow). A number of studies have investigated the association between the
      genotypes and phenotypes of EPHX1 and COPD susceptibility in different
      populations, with inconsistent results. A systematic review and meta-analysis of
      the published data was performed to gain a clearer understanding of this
      association. METHODS: The MEDLINE database was searched for case-control studies
      published from 1966 to August 2007. Data were extracted and pooled odds ratios
      (OR) with 95% confidence intervals (CI) were calculated. RESULTS: Sixteen
      eligible studies, comprising 1847 patients with COPD and 2455 controls, were
      included in the meta-analysis. The pooled result showed that the EPHX1 113 mutant
      homozygote was significantly associated with an increased risk of COPD (OR 1.59,
      95% CI: 1.14-2.21). Subgroup analysis supported the result in the Asian
      population, but not in the Caucasian population. When the analysis was limited to
      only the larger-sample-size studies, studies in which controls were in Hardy
      Weinberg equilibrium and studies in which controls were smokers/ex-smokers, the
      pooled results supported the conclusion. The EPHX1 139 heterozygote protected
      against the development of COPD in the Asian population, but not in the Caucasian
      population. The other gene types of EPHX1 113 and EPHX1 139 were not associated
      with an increased risk of COPD. The slow activity phenotype of EPHX1 was
      associated with an increased risk of COPD. The fast activity phenotype of EPHX1
      was a protective factor for developing COPD in the Asian population, but not in
      the Caucasian population. However, the very slow activity phenotype of EPHX1 was
      a risk for developing COPD in the Caucasian population, but not in the Asian
      population. CONCLUSIONS: The polymorphisms of EPHX1 113 and EPHX1 139 are genetic
      contributors to COPD susceptibility in Asian populations. The phenotypes of EPHX1
      were contributors to overall COPD susceptibility.

PMID- 18811883
TI  - Predictors of long-term survival in elderly patients hospitalized for acute
      exacerbations of chronic obstructive pulmonary disease.
AB  - BACKGROUND AND OBJECTIVE: There is a paucity of survival data regarding the
      prognosis of elderly patients following acute exacerbations of COPD (AECOPD). We
      undertook a study to examine long-term mortality rates and to identify clinical
      and laboratory predictors of these outcomes. METHODS: A retrospective cohort
      study was conducted of 786 consecutive elderly (>65 years) patients admitted to
      general medicine acute-care wards for AECOPD. Factors determining short- and long
      term mortality were analysed. RESULTS: The mean (+/-SD) age of the study
      population was 75.8 +/- 7.3 years (range 65-100 years). The in-hospital mortality
      rate for the entire cohort was 7.25%. The risk of mortality at 1, 3 and 5 years
      was 28%, 47% and 54%, respectively. In univariate analysis age (hazard ratio
      1.52; 95% confidence interval: 1.23-1.91), FEV(1) (1.45; 1.73-2.35), active
      cancer (1.23; 1.64-2.32), current smoking (1.74; 1.35-2.11), ischaemic heart
      disease (1.58; 1.28-2.02), congestive heart failure (1.55; 1.23-2.26) and
      maintenance use of oral glucocorticosteroids (1.58; 1.11-2.79) were significantly
      associated with mortality. In multivariate analysis, only current smoking (1.89;
      1.18-1.93), ischaemic heart disease (1.41; 1.07-1.68), PaCO(2) on admission
      (1.49; 1.03-1.60), hospital readmission (2.23; 1.40-2.18) and FEV(1) (1.41; 1.12
      1.54) were independent predictors of mortality. CONCLUSIONS: This study provides
      new insights into the predictive factors associated with long-term prognosis in
      elderly patients admitted for acute exacerbations of COPD, which differ from
      those previously identified for younger patients.

PMID- 18811884
TI  - Relationship between field walking tests and incremental cycle ergometry in COPD.
AB  - BACKGROUND AND OBJECTIVE: Cycle ergometer training is an important component of
      pulmonary rehabilitation for patients with COPD. However, incremental cycle tests
      from which individualized cycle training intensity can be prescribed may not be
      readily available to clinicians. The aims of the study were to (i) investigate
      the physiological and psychophysical responses to the 6-min walk test (6MWT),
      incremental shuttle walk test (ISWT) and cycle ergometer test (CET); and (ii)
      determine whether the distance walked in either the 6MWT or the ISWT could be
      used to estimate peak work rate on a cycle ergometer. METHODS: A repeated
      measures study was undertaken in COPD patients in a stable condition. The 6MWT,
      ISWT and CET were performed in random order, and physiological responses, rate of
      perceived exertion and dyspnoea were measured. RESULTS: Twenty-two patients with
      COPD completed the study. There was no significant difference in peak oxygen
      uptake between the 6MWT, ISWT and CET. The significant correlation between the
      6MWD and incremental shuttle walk distance with peak watts on the CET (r = 0.63,
      P = 0.002 and r = 0.75, P < 0.001, respectively) was strengthened by the
      inclusion of weight, age and gender (r = 0.89 P = 0.001 and r = 0.91, P < 0.001).
      Bland-Altman analysis demonstrated a strong agreement between peak work rate
      measured on the CET and that estimated from either the 6MWT or the ISWT.
      CONCLUSIONS: The significant relationships found between the three exercise
      tests, and the regression equations predicting peak work rate on the CET from the
      6MWT or the ISWT, may allow for the estimation of intensity of cycle exercise
      training from walk tests in COPD patients.

PMID- 18811885
TI  - Transbronchial biopsy is clinically useful in classifying patients with
      interstitial pneumonia associated with polymyositis and dermatomyositis.
AB  - BACKGROUND AND OBJECTIVE: The histological type of intraluminal fibrosis is an
      important prognostic factor for interstitial pneumonia. We therefore examined
      whether transbronchial lung biopsy (TBLB) specimens are useful for predicting the
      clinical course and prognosis of patients with interstitial pneumonia associated
      with polymyositis and dermatomyositis (PM/DM), with particular attention to the
      different types of intraluminal fibrosis. METHODS: Twenty-five cases of
      interstitial pneumonia associated with PM/DM were classified according to the
      pattern of intraluminal fibrosis as assessed by TBLB, and the clinical course and
      response to treatment were compared. Interstitial fibrosis was evaluated by
      sequential thin-section CT scans. RESULTS: In 19 of 25 (76%) cases, there was
      sufficient intraluminal fibrosis to perform an evaluation. Intraluminal fibrosis
      was classified as bud (polyp) type or mural incorporation type (either alone or
      mixed with bud type). The bud type was seen in five cases and these improved
      following treatment with corticosteroids only. The mural incorporation type was
      seen in 14 cases. In 11 of these 14 cases, progressive long-term fibrosis
      developed and four cases were fatal, in spite of corticosteroid and
      immunosuppressive therapy. The response to drugs (P < 0.01) and survival (P <
      0.05) were significantly greater in patients with bud-type than mural
      incorporation-type intraluminal fibrosis. CONCLUSIONS: Classification of the
      pattern of intraluminal fibrosis as assessed by TBLB is useful for predicting the
      response to treatment, clinical course and prognosis of interstitial pneumonia
      associated with PM/DM.

PMID- 18811886
TI  - Cross-sectional and longitudinal construct validity of the Saint George's
      Respiratory Questionnaire in patients with IPF.
AB  - BACKGROUND AND OBJECTIVE: This study was performed to confirm the cross-sectional
      and longitudinal construct validity of the Saint George's Respiratory
      Questionnaire (SGRQ) for the measurement of health-related quality of life
      (HRQoL) in patients with IPF. METHODS: Sixty-eight patients with IPF responded to
      the SGRQ and pulmonary function tests (PFT), dyspnoea testing, arterial blood gas
      analysis, 6-min walk tests (6MWT) and high-resolution computed tomography were
      performed in a baseline study. A follow-up study was performed on 45 of these
      patients. RESULTS: In the baseline study HRQoL as measured by the SGRQ was
      substantially impaired in IPF patients, especially in symptoms and activity
      domains. A significant decline in HRQoL was observed in the activity domain
      during follow up. TLC and changes in TLC showed the most significant inverse
      correlations with each SGRQ domain (r < -0.3, P < 0.05). In a stepwise multiple
      regression analysis, TLC contributed most significantly to each SGRQ component
      baseline score. Similar results were also observed during follow up. There was a
      significant correlation between total CT scores and each component of the SGRQ (r
      > 0.3, P < or = 0.001). Changes in ground-glass opacity on CT (CT-alv) were also
      correlated with changes in each SGRQ domain (r > 0.3, P < or = 0.001). Stepwise
      multiple regression analysis showed that interstitial opacity on CT (CT-fib)
      contributed to variation in the baseline activity score, and that changes in CT
      alv independently contributed to overall changes in the SGRQ domains during
      follow up. The dyspnoea score, and changes in the dyspnoea score, correlated
      significantly with the SGRQ sores, with the exception of the symptoms score, in
      both the baseline and follow-up studies. CONCLUSIONS: HRQoL as assessed by the
      SGRQ showed good cross-sectional and longitudinal construct validity in patients
      with IPF. However, additional studies are required to analyse the reliability and
      responsiveness so that the SGRQ can be used in patients with IPF.

PMID- 18811887
TI  - Poor clinical outcomes associated with a multi-drug resistant clonal strain of
      Pseudomonas aeruginosa in the Tasmanian cystic fibrosis population.
AB  - BACKGROUND AND OBJECTIVE: Clonal strains of Pseudomonas aeruginosa have been
      identified in large cystic fibrosis (CF) centres. Whether such strains are more
      virulent or whether cross-infection between patients explains their widespread
      prevalence is unknown. This study described the epidemiology of P. aeruginosa
      infection in CF patients in Tasmania, Australia, an area with a high CF birth
      incidence. Patients in Tasmania are geographically dispersed and when this study
      was conducted (2003) there was no central CF clinic, with patients receiving
      treatment in regional hospitals. METHODS: P. aeruginosa isolates from CF adults
      aged 15 years and over in Tasmania were genotyped using random amplified
      polymorphic DNA (RAPD)-PCR and clonal strains confirmed with pulsed field gel
      electrophoresis. RESULTS: Airway samples were obtained from 41 patients (82% of
      the adult CF population). P. aeruginosa was isolated from 34 patients and nine
      (26%) of these individuals harboured P. aeruginosa strains with identical RAPD
      PCR and pulsed field gel electrophoresis patterns (Australian Epidemic Strain III
      -AES III). AES III was isolated from patients in all regions of Tasmania and was
      distinct from the epidemic CF strains described on mainland Australia (AES I and
      II). The possible link between CF adults infected with AES III was attendance at
      family camps more than 12 years previously. Patients harbouring AES III had
      suffered significantly more exacerbations requiring hospitalisation during the 2
      years prior to the study compared with patients infected with unique strains (P <
      0.01). AES III displayed increased multi-antibiotic resistance compared with
      other strains (P < 0.001). CONCLUSIONS: Clonal strains of P. aeruginosa may arise
      even in isolated CF populations. The increased exacerbation rate in patients
      infected with AES III and its antibiotic resistance profile strongly suggest
      increased virulence.

PMID- 18811888
TI  - Limited role for outpatient parenteral antibiotic therapy for community-acquired
      pneumonia.
AB  - BACKGROUND AND OBJECTIVE: This study examined the potential utility of outpatient
      parenteral antibiotic therapy (OPAT) as a means of reducing the excessive number
      of patients hospitalized with low-risk community-acquired pneumonia (CAP).
      METHODS: A prospective feasibility study was conducted, in which a selection
      algorithm was applied to a cohort of patients admitted with suspected CAP, to
      identify a group in whom admission may have been prevented by the use of OPAT.
      Numbers of potentially suitable patients, inpatient bed days saved and frequency
      of adverse events that may have led to readmission were measured. RESULTS: There
      were 118 inpatients treated with confirmed CAP during the study period, of whom
      27 had low-risk disease (Pneumonia Severity Index grades I-III). Application of
      the selection algorithm identified eight (30% of those with low-risk disease)
      patients who were potentially suitable for OPAT, and this group commonly
      experienced adverse events during follow up which may have resulted in
      readmission to hospital. CONCLUSIONS: In many hospitalized patients with CAP,
      outpatient therapy is precluded by either disease severity or active medical and
      psychosocial factors. This limits the role of OPAT as a tool for reducing the
      inpatient burden of CAP.

PMID- 18811889
TI  - Lung transplantation in Hong Kong: 12 years of experience.
AB  - BACKGROUND AND OBJECTIVE: A lung transplant programme was launched in August 1994
      at Grantham Hospital in Hong Kong with the first single-lung transplant performed
      in July 1995. A retrospective study was undertaken of all patients who had
      undergone lung transplantation and their outcomes analysed. METHODS: Data were
      collected from hospital and outpatient records. RESULTS: There were 12
      transplants (two single-lung and 10 double-lung) performed in the 12 years to
      December 2006. No postoperative or early mortality was observed. In addition to
      the usual complications there were two cases of early pulmonary tuberculosis and
      one rare case of delayed fungal sternotomy infection. The 1-year, 3-year and 5
      year survival rates were 100%, 100% and 76.2%, respectively. All fatalities were
      related to the consequences of chronic rejection or its treatment. CONCLUSIONS:
      Despite the limited experience and the small case volume, the survival of
      patients was good and comparable with international experience.

PMID- 18811890
TI  - Clinical characteristics and efficacy of bronchoscopic intervention for
      tracheobronchial leiomyoma.
AB  - BACKGROUND AND OBJECTIVE: This study reports the clinical characteristics,
      efficacy and safety of bronchoscopic treatment of patients with tracheobronchial
      leiomyoma. METHODS: A retrospective study of 10 patients with tracheobronchial
      leiomyoma who underwent bronchoscopic intervention between 2000 and 2007 at a
      single centre, documenting the clinical characteristics, treatment method and
      outcomes. RESULTS: Seven men and three women were studied. The median age at
      diagnosis was 47 years (range 17-66). The most frequent symptoms were cough (n =
      5) and dyspnoea (n = 4). The lesions were in the trachea in two patients, the
      right bronchi in six, and the left bronchi in two. On chest CT, the most frequent
      findings were a tracheobronchial mass without parenchymal lesion (n = 7). The
      tumours were removed by neodymium-yttrium-aluminum-garnet laser treatment by
      rigid bronchoscopy under general anaesthesia (n = 9) and with flexible
      bronchoscopy under local (n = 1) anaesthesia. Two patients eventually underwent
      surgical resection because of late tumour recurrence at 16 months, after the
      bronchoscopic intervention, in one patient, and incomplete removal by
      bronchoscopic intervention in another patient. In eight of ten patients who were
      successfully treated by the bronchoscopic intervention, the clinical outcome was
      good during the median follow-up period of 24.5 months. There were no procedure
      related mortalities or late complications. CONCLUSIONS: Patients with a
      tracheobronchial leiomyoma usually present with non-specific respiratory symptoms
      and an endobronchial mass without parenchymal lesions. Bronchoscopic intervention
      is a safe and effective technique for the treatment of patients with a
      tracheobronchial leiomyoma.

PMID- 18811891
TI  - Combination therapy with prostacyclin and tadalafil for severe pulmonary arterial
      hypertension: a pilot study.
AB  - Despite the introduction of new drugs that have changed the course of pulmonary
      arterial hypertension (PAH), some patients are still refractory to treatment and
      deteriorate rapidly. Long-acting phosphodiesterase-5 inhibitors are a new class
      of drugs that are effective in PAH. This prospective study assessed the potential
      of combination therapy with prostacyclin and tadalafil for treatment of severe
      PAH. We report four cases of severe PAH that deteriorated despite prostacyclin
      therapy. Two patients had Eisenmenger syndrome, one had pulmonary hypertension
      associated with scleroderma and one had histiocytosis X. All were treated with
      tadalafil, 10-20 mg once daily, in addition to prostacyclin. After 3 months of
      treatment, all patients improved clinically, with an increase in mean 6MWD from
      214 to 272 m. In three patients, the New York Heart Association functional class
      decreased from IV to III. Echocardiograms showed no significant changes in
      pulmonary arterial pressure. Although this study was limited by the small sample
      size, it suggests that tadalafil in combination with prostacyclin is an effective
      treatment for severe PAH. Tadalafil may be beneficial for the treatment of
      patients with advanced disease.

PMID- 18811892
TI  - Pulmonary hypertension responding to hyperthyroidism treatment.
AB  - Pulmonary hypertension in adults with hyperthyroidism is increasingly being
      reported. Although the mechanism is uncertain, the reversal of pulmonary
      hypertension following restoration to an euthyroid state supports a causal
      relationship. This case report is of a 43-year-old woman who presented with
      Graves disease and right ventricular failure. Echocardiography showed severe
      pulmonary hypertension, moderate to severe tricuspid regurgitation, normal left
      heart function and a negative bubble contrast study. Carbimazole therapy was
      instituted along with diuretics and captopril. The patient was followed for a
      period of 14 months. Clinical and biochemical euthyroidism was attained after 4
      months of treatment. Resolution of right ventricular failure and normalization of
      pulmonary artery pressure occurred 11 and 14 months after initiation of therapy,
      respectively. Investigating thyroid status in patients with pulmonary
      hypertension is recommended. In patients with hyperthyroidism and (otherwise
      unexplained) pulmonary hypertension, restoration of euthyroidism may cure right
      ventricular failure and restore normal pulmonary artery pressure.

PMID- 18811893
TI  - Predicting impairment of diffusing capacity for Chinese patients with lung
      fibrosis.

PMID- 18811894
TI  - Environmental asbestos exposure alters the male:female ratio in patients with
      pleural mesothelioma.

PMID- 18811896
TI  - Transfusion-associated immune modulation: a reason to TRIM platelet transfusions?

PMID- 18811897
TI  - Transfusion medicine illustrated. Clumping in an apheresis-collected peripheral
      blood progenitor cell product.

PMID- 18811898
TI  - Transfusion-transmitted human immunodeficiency virus infection by a Danish blood
      donor with a very low viral load in the preseroconversion window phase.

PMID- 18811899
TI  - Red blood cell age and function.

PMID- 18811900
TI  - Length of cord blood unit cryopreservation does not impact hematopoietic
      engraftment.

PMID- 18811902
TI  - Zoonoses and public health. Zoonoses associated with our animal companions. Guest
      editorial.

PMID- 18811903
TI  - Meeting report: panel on the potential utility and strategies for design and
      implementation of a national companion animal infectious disease surveillance
      system.
AB  - This meeting report summarizes the discussions and recommendations of a Blue
      Ribbon Panel convened by the Science and Technology Policy Institute at the
      Institute for Defense Analysis on behalf of the White House Office of Science and
      Technology Policy (OSTP) on 13 September 2006 to discuss the potential utility
      and possible strategies for design and implementation of a companion animal
      health surveillance system. The panel comprised representatives from federal
      agencies, state agencies, academia, professional societies, and the private
      sector. The panel concluded that a companion animal surveillance system might
      prove valuable to efforts to protect public health, but that further study of the
      relationship between companion animal health and human health were needed to
      assess the utility and potential applications of a companion animal surveillance
      system. The findings of this panel may be used, along with other important
      sources of information, to inform policy discussions focussed on identifying
      strategies for recognizing and monitoring zoonotic disease threats appearing in
      companion animals in the USA.

PMID- 18811904
TI  - Survey of owned feline and canine populations in apartments from a neighbourhood
      in Curitiba, Brazil.
AB  - Animal population estimates are essential for public health services to ensure
      the success of zoonoses control programmes. Canine and feline populations vary
      among different regions mainly because of local human income status and type of
      human residence. Accordingly, the present study estimated the pet population size
      living in apartments of a vertical neighbourhood in Curitiba, Brazil. We chose a
      neighbourhood with a predominance of apartment buildings. All apartment buildings
      were visited, and questionnaires were completed by doormen or residents. Data
      were obtained from 120 of 173 apartment buildings. Survey questions included the
      number of apartments, residents, dogs and cats. Two thousand nine hundred and
      sixty six apartments with a total of 7429 residents were surveyed. The number of
      dogs and cats was 569 and 86 respectively. Thus, the human:dog and human:cat
      ratios were 13.05:1 and 86.38:1. These ratios were higher than those observed in
      other neighbourhoods in Curitiba. The present study indicates that the number of
      pets from apartments may be different from houses, and different among distinct
      areas within the same city.

PMID- 18811905
TI  - Prevalence of dog intestinal parasites and risk perception of zoonotic infection
      by dog owners in Sao Paulo State, Brazil.
AB  - Coprological examination was used to estimate the prevalence of gastrointestinal
      parasites in stray and domiciled dogs from Botucatu, Sao Paulo State, Brazil.
      Risk factors for dog infection were assessed in relation to demographic,
      husbandry and management data. The dog owners completed a questionnaire survey on
      some aspects of dog parasitism such as parasite species, mechanisms of infection,
      awareness of zoonotic diseases and history of anthelmintic usage. Parasites were
      found in the faeces of 138 dogs, with an overall prevalence of 54.3%. Dogs
      harbouring one parasite were more common (31.4%) than those harbouring two
      (18.5%), three (3.2%) or four (1.2%). The following parasites and their
      respective frequencies were detected: Ancylostoma (37.8%), Giardia (16.9%),
      Toxocara canis (8.7%), Trichuris vulpis (7.1%), Dipylidium caninum (2.4%),
      Isospora (3.5%), Cryptosporidium (3.1%) and Sarcocystis (2.7%). Stray dogs were
      found more likely to be poliparasitized (P<0.01) and presented higher prevalence
      of Ancylostoma, T. canis and Giardia (P<0.01) than domiciled ones. Toxocara canis
      was detected more frequently in dogs with <6 months of age (P<0.05) and no effect
      of sex or breed could be observed (P>0.05). Except for Ancylostoma, that showed a
      significantly higher prevalence in dogs living in a multi-dog household (P<0.01),
      parasite prevalences were similar in single- and multi-dog household. The answers
      of dog owners to the questionnaire showed that the majority does not know the
      species of dog intestinal parasites, the mechanisms of transmission, the risk
      factors for zoonotic infections, and specific prophylactic measures. The
      predominance of zoonotic species in dogs in the studied region, associated with
      the elevated degree of misinformation of the owners, indicates that the risk of
      zoonotic infection by canine intestinal parasite may be high, even in one of the
      most developed regions of Brazil.

PMID- 18811906
TI  - The first laboratory-confirmed rabid pig in Maryland, 2003.
AB  - This article is the first to describe the clinical picture and potential human
      health impact of laboratory-confirmed rabies infection in a pet Vietnamese pot
      bellied pig in Maryland. Although cases of confirmed rabies infection have been
      infrequently reported in pet or agricultural during the past 10 years in the
      United States, exposure to rabies-positive animals remains a public health
      concern particularly for veterinarians, pet owners and other animal caretakers.
      It is important that individuals who are in a high-risk rabies exposure group
      remain vigilant to this potential public health threat in all mammal species.

PMID- 18811907
TI  - The occurrence and antimicrobial susceptibility of salmonellae isolated from
      commercially available canine raw food diets in three Canadian cities.
AB  - The purpose of the present study was to evaluate the prevalence and antimicrobial
      resistance patterns of Salmonella isolated from commercially available canine raw
      food diets in Canada. A total of 166 commercial frozen raw food diet samples were
      purchased from randomly selected local pet stores in three Canadian cities for a
      period of 8 months. All samples were evaluated for the presence of Salmonella,
      serotyped and tested for antimicrobial susceptibility. There was an overall
      Salmonella prevalence of 21%; chicken was an ingredient for 67% of the Salmonella
      positive diets. Eighteen different Salmonella serotypes were recovered, and
      resistance was observed to 12 of the 16 antimicrobials tested, with the majority
      of Ontario isolates exhibiting resistance to ampicillin and Calgary isolates to
      tetracycline. This study demonstrates the potential risk of raw food diets,
      especially for immunocompromised individuals, and stresses the need for
      implementing regulatory guidelines for the production of these diets in order to
      help control and ideally eliminate the bacterial risks associated with their use
      and consumption.

PMID- 18811908
TI  - Evaluation of the risks of shedding Salmonellae and other potential pathogens by
      therapy dogs fed raw diets in Ontario and Alberta.
AB  - Dogs that participate in animal-assisted interventions (AAIs), often called
      'therapy dogs', commonly interact with humans whose immune systems are not
      functioning optimally. The advisability of feeding raw meat (including poultry)
      to these animals remains a highly contentious issue, in spite of increasing
      evidence that raw meat is frequently contaminated with Salmonella. We set out to
      determine if consuming raw meat influences the risk of therapy dogs shedding
      Salmonella and other pathogens. Two hundred healthy therapy dogs from Ontario and
      Alberta were enrolled. Between May 2005 and November 2006, fecal specimens were
      collected from each dog every 2 months for 1 year, along with a log of places
      visited, antimicrobial use within the home, dog health status and diet. Specimens
      were cultured for Salmonella, methicillin-resistant Staphylococcus aureus (MRSA),
      vancomycin-resistant enterococci (VRE), extended-spectrum cephalosporinase (ESC)
      Escherichia coli and Clostridium difficile. Forty (20%) of the dogs were reported
      to have been fed raw meat at some point during the year. The incidence rate of
      Salmonella shedding in the raw meat-fed dogs was 0.61 cases/dog-year, compared
      with 0.08 cases/dog-year in dogs that were not fed raw meat (P<0.001).
      Controlling for therapy dog group, the repeated measures, and pig ear consumption
      and diarrhoea in the 2 months prior to specimen submission, dogs that consumed
      raw meat were significantly more likely to test positive for Salmonella at least
      once during the year than dogs that did not eat raw meat [odds ratio (OR) 22.7;
      95% confidence interval (CI) 3.1-58.8; P<0.001]. Specific Salmonella serovars
      were more common among dogs that consumed raw meat versus those that did not
      include S. Typhimurium, S. Heidelberg and S. Kentucky. Raw meat consumption was
      also significantly associated with shedding ESC E. coli (OR 17.2; 95% CI 9.4
      32.3). No associations between C. difficile, MRSA or VRE and consumption of raw
      meat were detected. We recommend that dogs fed raw meat should be excluded from
      AAI programmes, particularly when the programmes involve interaction with humans
      at high risk of infection or adverse sequelae attributable to infection.
      Furthermore, although AAI dogs may not be representative of the general
      population of dogs, we also recommend that feeding of raw meat to dogs is to be
      avoided in homes where immunocompromised people live.

PMID- 18811909
TI  - Investigation and characterization of the frozen feeder rodent industry in Texas
      following a multi-state Salmonella Typhimurium outbreak associated with frozen
      vacuum-packed rodents.
AB  - A multi-state outbreak investigation of Salmonella Typhimurim cases associated
      with pet snakes and the frozen vacuum-packed rodents used to feed them identified
      a Texas frozen feeder rodent facility (Supplier A) as the source of the
      Salmonella-infected frozen rodents. Texas authorities collected samples directly
      from Supplier A. Seven Salmonella-positive samples out of 49 environmental swabs
      were found and one adult mouse out of 88 frozen feeder rodents was Salmonella
      positive by culture. No Salmonella strains were isolated from rodent feeds. The
      pulsed-field gel electrophoresis (PFGE) subtype patterns of S. Typhimurium
      isolates from feeder rodent and environment samples were indistinguishable from
      the outbreak strain isolated from humans. A follow-up investigation was performed
      on all additional feeder rodent facilities identified in Texas. Salmonella was
      isolated at one of four facilities; seven of 100 rodent samples were positive for
      Salmonella at this facility. The serotype S. I 4,[5],12:i:- was isolated from
      seven feeder rodent samples, and PFGE patterns of the seven isolates were
      indistinguishable. As observed in the initial outbreak investigation, no
      Salmonella were cultured from rodent feeds at any of the facilities. The feeder
      rodent industry is an insufficiently recognized industry in the United States.
      Outbreak investigation and testing of additional feeder rodent facilities in
      Texas indicate that further evaluation of feeder rodent facilities as a source of
      Salmonella for pet snakes and humans is warranted.

PMID- 18811910
TI  - Why your housecat's trite little bite could cause you quite a fright: a study of
      domestic felines on the occurrence and antibiotic susceptibility of Pasteurella
      multocida.
AB  - Approximately four to five million animal bite wounds are reported in the USA
      each year. Domestic companion animals inflict the majority of these wounds.
      Although canine bites far outnumber feline bites, unlike the dog, the cat's bite
      is worse than its bark; 20-80% of all cat bites will become infected, compared
      with only 3-18% of dog bite wounds. Pasteurella multocida is the most commonly
      cultured bacterium from infected cat bite wounds. Anyone seeking medical
      attention for a cat-inflicted bite wound is given prophylactic/empiric penicillin
      or a derivative to prevent Pasteurella infection (provided they are not allergic
      to penicillins). In an effort to establish a carriage rate of P. multocida in the
      domestic feline, bacterial samples from the gingival margins of domestic northern
      Ohio cats (n=409) were cultured. Isolates were tested for antibiotic sensitivity
      as prophylactic/empiric use of penicillin and its derivatives could potentially
      give rise to antibiotic resistance in P. multocida. The high carriage rate
      (approximately 90%) of P. multocida observed was found to be independent of
      physiological and behavioural variables including age, breed, food type, gingival
      scale, lifestyle and sex. High antibiotic susceptibility percentages were
      observed for benzylpenicillin, amoxicillin-clavulanate, cefazolin, and
      azithromycin (100%, 100%, 98.37% and 94.02%, respectively) in P. multocida
      isolates. The high prevalence of P. multocida in the feline oral cavity indicates
      that prophylactic/empiric antibiotic therapy is still an appropriate response to
      cat bite wounds. Additionally, the susceptibility of P. multocida to penicillin
      and its derivatives indicates that they remain reliable choices for preventing
      and treating P. multocida infections.

PMID- 18811911
TI  - A chilly breeze leads to heavy breathing - facial cooling and the human
      peripheral chemoreflex.

PMID- 18811912
TI  - Elevated plasma ACE activity: no guarantee for enhanced left ventricular
      hypertrophy during training.

PMID- 18811915
TI  - Benign prostatic hyperplasia due to venous drainage malfunction in the male
      reproductive system: a price of erect posture in humans.

PMID- 18811916
TI  - Reversal of benign prostate hyperplasia by selective occlusion of impaired venous
      drainage in the male reproductive system: novel mechanism, new treatment.
AB  - The prostate is an androgen-regulated exocrine gland producing over 30% of the
      noncellular components of the semen and promoting optimal conditions for survival
      and motility of sperm in the vagina. Benign prostate hyperplasia (BPH) is the
      most common benign neoplasm in men. Its aetiology is not clear, and therefore,
      current medical treatments are directed towards the symptoms. Though testosterone
      is known to be the promoter of prostate cell proliferation, no causal relation
      between serum testosterone levels and BPH has been found. In this study, we
      propose a novel and tested pathophysiological mechanism for the evolution of BPH
      and suggest a tested and effective treatment. We found that in all BPH patients,
      the one-way valves in the vertically oriented internal spermatic veins are
      destroyed (clinically manifested as varicocele), causing elevated hydrostatic
      pressure, some 6-fold greater than normal, in the venous drainage of the male
      reproductive system. The elevated pressure propagates to all interconnected
      vessels leading to a unique biological phenomenon: venous blood flows retrograde
      from the higher pressure in the testicular venous drainage system to the low
      pressure in the prostatic drainage system directly to the prostate (law of
      communicating vessels). We have found that free testosterone levels in this blood
      are markedly elevated, with a concentration of some 130-fold above serum level.
      Consequently, the prostate is exposed to: (i) increased venous pressure that
      causes hypertrophy; (ii) elevated concentration of free testosterone causing
      hyperplasia. We have treated 28 BPH patients using a technique that restores
      normal pressure in the venous drainage in the male reproductive system. The back
      pressure and the back-flow of blood from the testicular to the prostate drainage
      system were eliminated and, consequently, a rapid reduction in prostate volume
      and a regression of prostate symptoms took place.

PMID- 18811917
TI  - Distribution of alpha-, gamma (+beta)- and delta-tocopherol in the seminal
      plasma, spermatozoa and seminal vesicles of rabbit.
AB  - Dietary vitamin E supplementation plays a key role in animal reproduction by
      protecting germ cells from oxidative damage. Recently, alpha-tocopherol
      homologues (namely, beta-, gamma- and delta-tocopherol) have been the object of
      increasing research because of their peculiar nonantioxidant properties. We found
      that these tocol-derived compounds are not homogeneously distributed among semen
      components. Alpha-T was the major vitamin E homologue found in all semen
      fractions. Half of the total gamma (+beta)-T was found in germ cells, while more
      than 50% of total delta-T was preferentially accumulated in seminal plasma. The
      concentration of various tocol-derived compounds depended on their relative
      amounts in diet and the competition for saturable enzymes implicated in their
      metabolism. A higher concentration of delta-T in seminal plasma may be related to
      its more polar nature. However, the biological function of this compound in semen
      remains to be cleared. To our knowledge, this is the first study aimed at
      identifying alpha-tocopherol homologues in rabbit semen fractions.

PMID- 18811918
TI  - Sperm ultrastructure and meiotic segregation in a group of patients with chronic
      hepatitis B and C.
AB  - Little is known about the effect of chronic hepatitis B and hepatitis C on sperm
      quality. In this study, we analysed sperm quality from selected patients with
      chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infections. Semen
      samples were examined by light and transmission electron microscopy (TEM). TEM
      data were elaborated with a mathematical formula able to indicate a fertility
      index and the presence of the three main sperm pathologies: apoptosis, immaturity
      and necrosis. Meiotic chromosome segregation was investigated by fluorescence in
      situ hybridisation carried out on sperm nuclei, using probes for chromosomes 18,
      X and Y. Despite normal sperm concentration, we observed reduced motility. TEM
      analysis highlighted that 35.7% of patients showed generally good semen quality.
      However, significantly higher values of apoptosis and necrosis, compared with
      controls, were observed, demonstrating spermatogenetic alterations. Regarding
      meiotic segregation, we found an incidence of disomies similar to that observed
      in control samples, whereas diploidy resulted higher in HCV patients, without
      reaching statistical significance. In conclusion, sperm quality in the studied
      group was not impaired; however, apoptosis and necrosis resulted out of normal
      range and the fertility index was significantly lower in HCV- and HBV-infected
      patients versus controls.

PMID- 18811919
TI  - Heme oxygenase enzyme activity in human seminal plasma of fertile and infertile
      males.
AB  - This work aimed to assess heme oxygenase (HO) enzyme activity relationship with
      different human semen parameters. One hundred and twenty men were divided
      according to their sperm count and clinical examination into: obstructive
      azoospermia (n = 20), nonobstructive azoospermia (NOA) (n = 25), oligozoospermia
      (n = 35) and normozoospermia (n = 40). Semen analysis, western blot for HO-1 and
      HO-2, and estimation of seminal plasma HO enzyme activity chemically in the form
      of bilirubin concentration were carried out. Seminal plasma HO enzyme activity
      was very low in OA specimens, low in NOA, moderate in oligozoospermia while
      higher in normozoospermia (mean +/- SD; 6.26 +/- 2.2, 81.4 +/- 35.5, 283.8 +/-
      90.1, 657.4 +/- 227.6 pmol ml(-1) min(-1)) with significant differences. Western
      blot analysis demonstrated HO-2 expression in all studied groups whereas HO-1 was
      highly expressed in fertile normozoospermic group compared with other groups.
      There was positive correlation between seminal plasma HO enzyme activity and
      sperm concentration, sperm motility percentage, motile spermatozoa ml(-1) and
      sperm normal morphology per cent. It is concluded that HO enzyme activity in the
      human seminal plasma is related to spermatogenesis and sperm-motility processes.

PMID- 18811920
TI  - Decline of plasma 5alpha-dihydrotestosterone (DHT) levels upon testosterone
      administration to elderly men with subnormal plasma testosterone and high DHT
      levels.
AB  - The study was performed to measure the impact of testosterone (T) administration
      on circulating levels of 5alpha-dihydrotestosterone (DHT). Group 1 (32 men; mean
      age 61 years; mean T 6.9 +/- 1.9 nmol l(-1)) were treated for 15 months with long
      acting T undecanoate. Group 2 (23 men, mean age 60 years, mean T 7.6 +/- 2.0 nmol
      l(-1)) were treated for 9 months with T gel. Plasma T and DHT were measured
      before and after 9 months T administration. In the men treated with T undecanoate
      plasma T and DHT were also measured after 12 and 15 months. Before T
      administration, plasma DHT ranged from 0.39 to 1.76 nmol l(-1) (0.30-1.90 nmol l(
      1)). Mean DHT declined upon T administration from 0.95 +/- 0.50 to 0.55 +/- 0.30
      nmol l(-1) (P < 0.05). With an arbitrary cut-off at 0.60 nmol l(-1), all 21
      values of DHT > 0.60 nmol l(-1) had fallen from 1.29 +/- 0.50 to 0.70 +/- 0.60
      nmol l(-1) (P < 0.01). Below this cut-off point 13 values rose and 21 fell upon T
      administration. Below this cut-off point values on average declined from 0.39 +/-
      0.12 to 0.30 +/- 0.14 nmol l(-1) (P < 0.05). The study revealed that in a cohort
      of elderly men with subnormal plasma T levels plasma DHT levels declined upon T
      administration when they were in the higher range of normal (>0.6 nmol l(-1)),
      with a profound shift of DHT/T ratios presumed to be an indicator of a reduced
      5alpha-reductase activity. Below plasma DHT levels of 0.6 nmol l(-1), responses
      of plasma DHT to T administration varied.

PMID- 18811921
TI  - Expression of E-SOD, GPX5 mRNAs and immunoexpression of Cu/ZnSOD in epididymal
      epithelial cells of finasteride-treated rats.
AB  - We studied the immunoexpression of Cu/Zn superoxide dismutase (Cu/ZnSOD) and
      mRNAs expression of extracellular superoxide dismutase (E-SOD), and epididymal
      specific glutathione peroxidase 5 (GPX5), in epithelial cells of caput and cauda
      epididymis of rats treated with finasteride, a steroid-based inhibitor of 5alpha
      reductase. The 5alpha-reductase is known to exist in two isoforms. Both 5alpha
      red1 and 5alpha-red2 catalyse the irreversible conversion of T into DHT.
      Formation of DHT in the epididymis is mostly due to the action of 5alpha-red2 and
      finasteride is more potent inhibitor of this isoform. Rats were treated with
      finasteride for 56 days covering the duration of one spermatogenesis (four cycles
      of the seminiferous epithelium). Although E-SOD mRNA is normally expressed in
      cells of cauda but not of caput epididymis, treatment with finasteride produced
      the E-SOD transcript in cells of caput epididymis too. The GPX5 transcript was
      detected in cells of caput epididymis of control and experimental rats, but the
      level of expression measured densitometrically was significantly lower in
      finasteride-treated rats. The immunoexpression of Cu/ZnSOD was also changed in
      epididymis of finasteride-treated rats. Finasteride appears to change the pattern
      of expression of antioxidant enzymes and may alter the protective function of the
      epididymis in relation to spermatozoa.

PMID- 18811922
TI  - Effect of repeated sequential ejaculation on sperm DNA integrity in subfertile
      males with asthenozoospermia.
AB  - The aim of this work was to study the possible beneficial effect of repeated
      sequential ejaculation on sperm DNA integrity in subfertile males and its
      possible implementation in assisted reproduction. The study included 20 infertile
      males with idiopathic asthenozoospermia or oligoasthenozoospermia. They underwent
      detailed history taking, complete clinical assessment and hormonal assessment.
      Patients were asked to bring two semen samples (taken within 1-3 h). Two
      consecutive samples were assessed with regard to semen volume, sperm count,
      motility grading, and morphology and sperm DNA integrity using the comet assay.
      There was a significant improvement in the sperm motility pattern and DNA
      integrity in the second sample in comparison with the first sample. Therefore, it
      is concluded that due to its positive impact on sperm motility and DNA integrity,
      repeated sequential ejaculation is recommended in subfertile males with
      idiopathic asthenozoospermia who pursue assisted reproduction.

PMID- 18811923
TI  - Geographical differences in semen quality in a population of young healthy
      volunteers from the different regions of Spain.
AB  - Numerous studies have shown geographical differences in semen quality even within
      a given country. We have previously reported a low semen quality in volunteers
      from the province of Barcelona compared with the general population. The
      objective of this study was to determine the semen quality in a population of
      young healthy volunteers from the different regions of Spain. A total of 1239
      volunteers between 18 and 30 years of age were enrolled. The parameters evaluated
      were semen volume, sperm concentration and progressive sperm motility. The
      results indicate that while there were no differences in semen volume or sperm
      motility, there were statistically significant differences in the rate of
      oligospermia in volunteers from the different regions studied. The prevalence of
      oligospermia was highest in Valencia (22.7%), Barcelona (22.7%) and Pais Vasco
      (18.7%), which are the regions of Spain with the highest degree of
      industrialisation for the last 50 years, and lowest in Galicia (8.5%) and
      Andalucia (13.7%), regions with a more recent industrial development. There were
      no differences in the rate of oligospermia as a function of age. These results
      support the hypothesis that exposure to environmental toxicants may affect the
      process of spermatogenesis leading to meiotic alterations, maturational arrest
      and oligospermia.

PMID- 18811924
TI  - High percentage of apoptotic spermatozoa in ejaculates from men with chronic
      genital tract inflammation.
AB  - Silent chronic inflammation of genital tract (CIGT) is considered as a major
      contributing factor to male fertility disorders. Within CIGT, inflammatory
      cytokines such as TNF-alpha might induce spermatozoal apoptosis, which in turn
      has been shown to have a negative influence on the sperm-oocyte penetration
      capacity. Thus, the aim of this study was to investigate spermatozoal apoptosis
      in patients with fertility disorders and signs of CIGT. Apoptosis of spermatozoa
      was determined by expression of annexin V using flow cytometry. Apoptotic
      spermatozoa were further discriminated from necrotic spermatozoa by 7-amino
      actinomycin (7AAD). Ejaculates of patients showing signs of CIGT (P-CIGT) such as
      high polymorphonuclear (PMN) elastase were compared to control ejaculates of
      patients lacking signs of CIGT (CON). Thereby we detected a significant
      correlation between PMN elastase and TNF-alpha in the seminal plasma and
      apoptotic spermatozoa. Furthermore, we demonstrated a significantly higher
      percentage of apoptotic spermatozoa in the ejaculate of P-CIGT compared to CON.
      Interestingly, a significantly higher percentage of apoptotic spermatozoa was
      detected in the swim-up fraction demonstrating motility of apoptotic spermatozoa.
      This is in line with the missing correlation of apoptotic spermatozoa and
      motility. In conclusion, patients with signs of CIGT display high numbers of
      apoptotic spermatozoa with progressive motility, which might have an impact on
      reproductive techniques such as intrauterine insemination or in-vitro
      fertilisation.

PMID- 18811925
TI  - Low grade epithelial stromal tumour of the seminal vesicle.
AB  - BACKGROUND: The mixed epithelial stromal tumour is morphologically characterised
      by a mixture of solid and cystic areas consisting of a biphasic proliferation of
      glands admixed with solid areas of spindle cells with variable cellularity and
      growth patterns. In previous reports the seminal vesicle cystoadenoma was either
      considered a synonym of or misdiagnosed as mixed epithelial stromal tumour. The
      recent World Health Organisation Classification of Tumours considered the two
      lesions as two distinct neoplasms. This work is aimed to present the low-grade
      epithelial stromal tumour case and the review of the literature to the extent of
      establishing the true frequency of the neoplasm. CASE PRESENTATION: We describe a
      low-grade epithelial stromal tumour of the seminal vesicle in a 50-year-old man.
      Computed tomography showed a 9 x 4.5 cm pelvic mass in the side of the seminal
      vesicle displacing the prostate and the urinary bladder. Magnetic resonance was
      able to define tissue planes between the lesion and the adjacent structures and
      provided useful information for an accurate conservative laparotomic surgical
      approach. The histology revealed biphasic proliferation of benign glands admixed
      with stromal cellularity, with focal atypia. After 26 months after the excision
      the patient is still alive with no evidence of disease. CONCLUSION: Cystoadenoma
      and mixed epithelial stromal tumour of seminal vesicle are two distinct
      pathological entities with different histological features and clinical outcome.
      Due to the unavailability of accurate prognostic parameters, the prediction of
      the potential biological evolution of mixed epithelial stromal tumour is still
      difficult. In our case magnetic resonance imaging was able to avoid an
      exploratory laparotomy and to establish an accurate conservative surgical
      treatment of the tumour.

PMID- 18811926
TI  - Born in Bradford, a cohort study of babies born in Bradford, and their parents:
      protocol for the recruitment phase.
AB  - BACKGROUND: Bradford, one of the most deprived cities in the United Kingdom, has
      a wide range of public health problems associated with socioeconomic deprivation,
      including an infant mortality rate almost double that for England and Wales.
      Infant mortality is highest for babies of Pakistani origin, who comprise almost
      half the babies born in Bradford. The Born in Bradford cohort study aims to
      examine environmental, psychological and genetic factors that impact on health
      and development perinatally, during childhood and subsequent adult life, and
      those that influence their parents' health and wellbeing. This protocol outlines
      methods for the recruitment phase of the study. METHODS: Most Bradford women
      attend for antenatal care and give birth at the Bradford Royal Infirmary, which
      has approximately 5,800 births per year. Women are eligible for recruitment if
      they plan to give birth here. Babies born from March 2007 are eligible to
      participate, recruitment is planned to continue until 2010. Fathers of babies
      recruited are invited to participate. Women are usually recruited when they
      attend for a routine oral glucose tolerance test at 26-28 weeks gestation.
      Recruitment of babies is at birth. Fathers are recruited whenever possible during
      the antenatal period, or soon after the birth. The aim is to recruit 10,000
      women, their babies, and the babies' fathers. At recruitment women have blood
      samples taken, are interviewed to complete a semi-structured questionnaire,
      weighed, and have height, arm circumference and triceps skinfold measured.
      Umbilical cord blood is collected at birth. Within two weeks of birth babies have
      their head, arm and abdominal circumference measured, along with subscapular and
      triceps skinfold thickness. Fathers self-complete a questionnaire at recruitment,
      have height and weight measured, and provide a saliva sample. Participants are
      allocated a unique study number. NHS numbers will be used to facilitate record
      linkage and access to routine data. A wide range of hospital and community
      sources is being accessed to provide data for the women and children. Data are
      checked for accuracy and consistency. CONCLUSION: Born in Bradford will increase
      understanding of the factors that contribute to health and wellbeing, and
      identify factors that influence differences in them between people of Pakistani
      and European origin.

PMID- 18811927
TI  - Effectiveness of a nurse-led case management home care model in Primary Health
      Care. A quasi-experimental, controlled, multi-centre study.
AB  - BACKGROUND: Demand for home care services has increased considerably, along with
      the growing complexity of cases and variability among resources and providers.
      Designing services that guarantee co-ordination and integration for providers and
      levels of care is of paramount importance. The aim of this study is to determine
      the effectiveness of a new case-management based, home care delivery model which
      has been implemented in Andalusia (Spain). METHODS: Quasi-experimental,
      controlled, non-randomised, multi-centre study on the population receiving home
      care services comparing the outcomes of the new model, which included nurse-led
      case management, versus the conventional one. Primary endpoints: functional
      status, satisfaction and use of healthcare resources. Secondary endpoints:
      recruitment and caregiver burden, mortality, institutionalisation, quality of
      life and family function. Analyses were performed at base-line, and at two, six
      and twelve months. A bivariate analysis was conducted with the Student's t-test,
      Mann-Whitney's U, and the chi squared test. Kaplan-Meier and log-rank tests were
      performed to compare survival and institutionalisation. A multivariate analysis
      was performed to pinpoint factors that impact on improvement of functional
      ability. RESULTS: Base-line differences in functional capacity - significantly
      lower in the intervention group (RR: 1.52 95%CI: 1.05-2.21; p = 0.0016) -
      disappeared at six months (RR: 1.31 95%CI: 0.87-1.98; p = 0.178). At six months,
      caregiver burden showed a slight reduction in the intervention group, whereas it
      increased notably in the control group (base-line Zarit Test: 57.06 95%CI: 54.77
      59.34 vs. 60.50 95%CI: 53.63-67.37; p = 0.264), (Zarit Test at six months: 53.79
      95%CI: 49.67-57.92 vs. 66.26 95%CI: 60.66-71.86 p = 0.002). Patients in the
      intervention group received more physiotherapy (7.92 CI95%: 5.22-10.62 vs. 3.24
      95%CI: 1.37-5.310; p = 0.0001) and, on average, required fewer home care visits
      (9.40 95%CI: 7.89-10.92 vs.11.30 95%CI: 9.10-14.54). No differences were found in
      terms of frequency of visits to A&E or hospital re-admissions. Furthermore,
      patients in the control group perceived higher levels of satisfaction (16.88;
      95%CI: 16.32-17.43; range: 0-21, vs. 14.65 95%CI: 13.61-15.68; p = 0,001).
      CONCLUSION: A home care service model that includes nurse-led case management
      streamlines access to healthcare services and resources, while impacting
      positively on patients' functional ability and caregiver burden, with increased
      levels of satisfaction. TRIAL REGISTRATION: ISRCTN44054549.

PMID- 18811928
TI  - Evolutionary history of the alpha2,8-sialyltransferase (ST8Sia) gene family:
      tandem duplications in early deuterostomes explain most of the diversity found in
      the vertebrate ST8Sia genes.
AB  - BACKGROUND: The animal sialyltransferases, which catalyze the transfer of sialic
      acid to the glycan moiety of glycoconjugates, are subdivided into four families:
      ST3Gal, ST6Gal, ST6GalNAc and ST8Sia, based on acceptor sugar specificity and
      glycosidic linkage formed. Despite low overall sequence identity between each
      sialyltransferase family, all sialyltransferases share four conserved peptide
      motifs (L, S, III and VS) that serve as hallmarks for the identification of the
      sialyltransferases. Currently, twenty subfamilies have been described in mammals
      and birds. Examples of the four sialyltransferase families have also been found
      in invertebrates. Focusing on the ST8Sia family, we investigated the origin of
      the three groups of alpha2,8-sialyltransferases demonstrated in vertebrates to
      carry out poly-, oligo- and mono-alpha2,8-sialylation. RESULTS: We identified in
      the genome of invertebrate deuterostomes, orthologs to the common ancestor for
      each of the three vertebrate ST8Sia groups and a set of novel genes named ST8Sia
      EX, not found in vertebrates. All these ST8Sia sequences share a new conserved
      family-motif, named "C-term" that is involved in protein folding, via an
      intramolecular disulfide bridge. Interestingly, sequences from Branchiostoma
      floridae orthologous to the common ancestor of polysialyltransferases possess a
      polysialyltransferase domain (PSTD) and those orthologous to the common ancestor
      of oligosialyltransferases possess a new ST8Sia III-specific motif similar to the
      PSTD. In osteichthyans, we have identified two new subfamilies. In addition, we
      describe the expression profile of ST8Sia genes in Danio rerio. CONCLUSION:
      Polysialylation appeared early in the deuterostome lineage. The recent release of
      several deuterostome genome databases and paralogons combined with synteny
      analysis allowed us to obtain insight into events at the gene level that led to
      the diversification of the ST8Sia genes, with their corresponding enzymatic
      activities, in both invertebrates and vertebrates. The initial expansion and
      subsequent divergence of the ST8Sia genes resulted as a consequence of a series
      of ancient duplications and translocations in the invertebrate genome long before
      the emergence of vertebrates. A second subset of ST8sia genes in the vertebrate
      genome arose from whole genome duplication (WGD) R1 and R2. Subsequent selective
      ST8Sia gene loss is responsible for the characteristic ST8Sia gene expression
      pattern observed today in individual species.

PMID- 18811929
TI  - Physical activity as an aid to smoking cessation during pregnancy: two
      feasibility studies.
AB  - BACKGROUND: Pharmacotherapies for smoking cessation have not been adequately
      tested in pregnancy and women are reluctant to use them. Behavioural support
      alone has a modest effect on cessation rates; therefore, more effective
      interventions are needed. Even moderate intensity physical activity (e.g. brisk
      walk) reduces urges to smoke and there is some evidence it increases cessation
      rates in non-pregnant smokers. Two pilot studies assessed i) the feasibility of
      recruiting pregnant women to a trial of physical activity for smoking cessation,
      ii) adherence to physical activity and iii) women' perceptions of the
      intervention. METHODS: Pregnant smokers volunteered for an intervention combining
      smoking cessation support, physical activity counselling and supervised exercise
      (e.g. treadmill walking). The first study provided six weekly treatment sessions.
      The second study provided 15 sessions over eight weeks. Physical activity levels
      and continuous smoking abstinence (verified by expired carbon monoxide) were
      monitored up to eight months gestation. RESULTS: Overall, 11.6% (32/277) of women
      recorded as smokers at their first antenatal booking visit were recruited. At
      eight months gestation 25% (8/32) of the women achieved continuous smoking
      abstinence. Abstinent women attended at least 85% of treatment sessions and 75%
      (6/8) achieved the target level of 110 minutes/week of physical activity at end
      of-treatment. Increased physical activity was maintained at eight months
      gestation only in the second study. Women reported that the intervention helped
      weight management, reduced cigarette cravings and increased confidence for
      quitting. CONCLUSION: It is feasible to recruit pregnant smokers to a trial of
      physical activity for smoking cessation and this is likely to be popular. A large
      randomised controlled trial is needed to examine the efficacy of this
      intervention.

PMID- 18811930
TI  - Life satisfaction in patients with long-term non-malignant pain - relating LiSat
      11 to the Multidimensional Pain Inventory (MPI).
AB  - BACKGROUND: The West-Haven Multidimensional Pain Inventory (MPI) can be used to
      describe behavioural and psychosocial consequences of long-term pain but little
      is known about how MPI items and MPI subgroups relate to goals that patients find
      important in rehabilitation. Life satisfaction measured by the LiSat-11 checklist
      can be defined as an individual's perception of the difference between his
      reality and his needs or wants. This difference can be considered a "goal
      achievement gap". This study investigates the relation of MPI to LiSat-11 with
      the aim to explore the possibility that LiSat-11 can be used to measure pain
      rehabilitation outcomes that are important from the patients' view. METHODS:
      Participators were patients (n = 294) referred to the Pain and Rehabilitation
      Clinic in Uppsala, Sweden. Measures used were LiSat-11, MPI and its Swedish
      version MPI-S. LiSat-11 domains were correlated to MPI scales. Cluster analysis
      was used to demonstrate MPI-S subgroups. Analysis of variance followed by post
      hoc analysis was used to investigate life satisfaction in the three MPI-S
      subgroups. RESULTS: The strongest positive correlation were found for the LiSat
      11 domains/MPI scales: psychological health/life control and contacts/social
      activities, and the strongest negative correlation for: psychological
      health/affective distress, partner relationship/punishing responses, somatic
      health/interference and leisure/interference. None or only little correlation was
      found between MPI scale pain severity and most LiSat-11 domains and satisfaction
      with life as a whole. Among the MPI-S subgroups, adaptive copers generally had
      better life satisfaction than the dysfunctional and the interpersonally
      distressed. CONCLUSION: Pain severity alone is a rather poor predictor of low
      life satisfaction. MPI and LiSat-11 partly supplement each other as tools to
      describe how functional impairments relate to life satisfaction domains, which
      may be relevant for identifying domains which the patients find important to
      improve. Furthermore, differences in life satisfaction between the MPI-S
      subgroups may help to identify functional domains that may be of particular
      importance in specialised rehabilitation programs.

PMID- 18811931
TI  - Locally relapsed and metastatic uterine leiomyoma: a case report.
AB  - INTRODUCTION: Benign metastasising leiomyoma refers to a type of lesion
      characterised by leiomyomatous alterations without any indication of malignancy.
      It presents as either a singular nodule or multiple nodules of proliferating
      smooth muscle cells and is generally found in the lungs of women who have
      undergone a hysterectomy. The purpose of this case report is to contribute to the
      knowledge of this rare disease by presenting evidence and experience of a patient
      case. In particular, this report seeks to investigate the therapeutic approaches
      in order to understand whether a standard of care can be prescribed and whether
      the use of prophylaxis therapy with progesterone as a follow-up to surgery serves
      as a reasonable treatment in certain cases diagnosed as benign metastasising
      leiomyoma. CASE PRESENTATION: We present the case of a 52-year-old Caucasian
      woman who developed a pelvic relapse and a pulmonary localisation of benign
      metastasising leiomyoma following a hysterectomy for myomatous uterus.
      CONCLUSION: Our literature review revealed a single case of the use of
      chemoprophylaxis as treatment of a benign metastasising leiomyoma. The role of
      chemoprophylaxis in preventing future recurrences remains unclear. The use of
      progesterone as an adjuvant therapy for benign metastasising leiomyoma could
      simply be palliative, with associated psychological benefits, or it could be of
      therapeutic significance.

PMID- 18811932
TI  - SSMap: a new UniProt-PDB mapping resource for the curation of structural-related
      information in the UniProt/Swiss-Prot Knowledgebase.
AB  - BACKGROUND: Sequences and structures provide valuable complementary information
      on protein features and functions. However, it is not always straightforward for
      users to gather information concurrently from the sequence and structure levels.
      The UniProt knowledgebase (UniProtKB) strives to help users on this undertaking
      by providing complete cross-references to Protein Data Bank (PDB) as well as
      coherent feature annotation using available structural information. In this
      study, SSMap - a new UniProt-PDB residue-residue level mapping - was generated.
      The primary objective of this mapping is not only to facilitate the two tasks
      mentioned above, but also to palliate a number of shortcomings of existent
      mappings. SSMap is the first isoform sequence-specific mapping resource and is up
      to-date for UniProtKB annotation tasks. The method employed by SSMap differs from
      the other mapping resources in that it stresses on the correct reconstruction of
      the PDB sequence from structures, and on the correct attribution of a UniProtKB
      entry to each PDB chain by using a series of post-processing steps. RESULTS:
      SSMap was compared to other existing mapping resources in terms of the
      correctness of the attribution of PDB chains to UniProtKB entries, and of the
      quality of the pairwise alignments supporting the residue-residue mapping. It was
      found that SSMap shared about 80% of the mappings with other mapping sources. New
      and alternative mappings proposed by SSMap were mostly good as assessed by manual
      verification of data subsets. As for local pairwise alignments, it was shown that
      major discrepancies (both in terms of alignment lengths and boundaries), when
      present, were often due to differences in methodologies used for the mappings.
      CONCLUSION: SSMap provides an independent, good quality UniProt-PDB mapping. The
      systematic comparison conducted in this study allows the further identification
      of general problems in UniProt-PDB mappings so that both the coverage and the
      quality of the mappings can be systematically improved for the benefit of the
      scientific community. SSMap mapping is currently used to provide PDB cross
      references in UniProtKB.

PMID- 18811933
TI  - A haplotype variation affecting the mitochondrial transportation of hMYH protein
      could be a risk factor for colorectal cancer in Chinese.
AB  - BACKGROUND: The human MutY homolog (hMYH), a DNA glycolsylase involved in the
      excision repair of oxidative DNA damage, is currently studied in colorectal
      cancer (CRC). We previously demonstrated a haplotype variant c.53C>T/c.74G>A of
      hMYH (T/A) increasing the risk for gastric cancer in Chinese. However, most
      investigations on correlation between hMYH and CRC are conducted in Western
      countries and the underlying mechanism has been poorly understood. METHODS: To
      determine whether the haplotype T/A variant of hMYH was related to colorectal
      carcinogenesis, we performed a case-control study in 138 colorectal cancer (CRC)
      patients and 343 healthy controls in a Chinese population. Furthermore, the C/G
      for wild-type, C/A or T/G for single base variant and T/A for haplotype variant
      hMYH cDNAs with a flag epitope tag were cloned into pcDNA3.1+ vector and
      transfected into cos-7 cell line. Their subcellular localizations were determined
      by immunofluorescence assay. RESULTS: It was found that the frequency of
      haplotype variant allele was statistically higher in CRC patients than that in
      controls (P = 0.02, odds ratio = 5.06, 95% confidence interval = 1.26 - 20.4).
      Similarly, significant difference of heterozygote frequency was indicated between
      the two groups (P = 0.019), while no homozygote was found. In addition,
      immunofluorescence analysis showed that hMYH protein with haplotype T/A variation
      presented in both nucleus and mitochondria, in contrast to the wild-type protein
      only converging in mitochondria. However, neither of the single missense
      mutations alone changed the protein subcelluar localization. CONCLUSION: Although
      preliminarily, these results suggest that: the haplotype variant allele of hMYH
      leads to a missense protein, which partly affects the protein mitochondrial
      transportation and results as nuclear localization. This observation might be
      responsible for the increased susceptibility to cancers, including CRC, in
      Chinese.

PMID- 18811934
TI  - PredGPI: a GPI-anchor predictor.
AB  - BACKGROUND: Several eukaryotic proteins associated to the extracellular leaflet
      of the plasma membrane carry a Glycosylphosphatidylinositol (GPI) anchor, which
      is linked to the C-terminal residue after a proteolytic cleavage occurring at the
      so called omega-site. Computational methods were developed to discriminate
      proteins that undergo this post-translational modification starting from their
      aminoacidic sequences. However more accurate methods are needed for a reliable
      annotation of whole proteomes. RESULTS: Here we present PredGPI, a prediction
      method that, by coupling a Hidden Markov Model (HMM) and a Support Vector Machine
      (SVM), is able to efficiently predict both the presence of the GPI-anchor and the
      position of the omega-site. PredGPI is trained on a non-redundant dataset of
      experimentally characterized GPI-anchored proteins whose annotation was carefully
      checked in the literature. CONCLUSION: PredGPI outperforms all the other
      previously described methods and is able to correctly replicate the results of
      previously published high-throughput experiments. PredGPI reaches a lower rate of
      false positive predictions with respect to other available methods and it is
      therefore a costless, rapid and accurate method for screening whole proteomes.

PMID- 18811935
TI  - A comparison of EQ-5D index scores using the UK, US, and Japan preference weights
      in a Thai sample with type 2 diabetes.
AB  - BACKGROUND: Data are scarce on the comparison of EQ-5D index scores using the UK,
      US, and Japan preference weights in other populations. This study was aimed to
      examine the differences and agreements between these three weights, psychometric
      properties including test-retest reliability, convergent and known-groups
      validity, and the impact of differences in the EQ-5D scores on the outcome of
      cost-utility analysis in Thai people. METHODS: A convenience sample of 303 type 2
      diabetic outpatients (18 years or older) from a cross-sectional study was
      examined. ANOVA and pos-hoc Bonferroni tests were used to determine the
      differences among the three EQ-5D scores. The agreements among the EQ-5D scores
      were assessed employing intraclass correlations coefficients (ICCs) and Bland
      Altman plots. The ICCs were utilized to examine the test-retest reliability.
      Spearman's rho correlation coefficients were used to assess the convergent
      validity between the EQ-5D scores and sociodemographic & clinical data, and
      health status. Mann-Whitney U tests were used to test the differences in EQ-5D
      scores between the known groups including HbA1c level (cut point of 7%), and the
      presence of diabetic complications namely neuropathy, retinopathy, nephropathy
      and cardiovascular diseases. Seven hypothetical decision trees were created to
      evaluate the impact of differences in the EQ-5D scores on the incremental cost
      utility ratio (ICUR). RESULTS: The US weights yielded higher scores than those of
      the UK and the Japan weights (p < 0.001, both), while the UK and the Japan
      weighted scores did not differ (p > 0.05). Both UK and US scores had more
      agreement with each other than with the Japan scores. Regarding psychometric
      properties, the Japan scheme provided better test-retest reliability, convergent
      and known-groups validity than both UK and US schemes. The variation in EQ-5D
      scores estimated from UK, US, and Japan preference weights had a marginal impact
      on ICUR (range: 1.23-6.32%). CONCLUSION: Since the Japan model showed more
      preferable psychometric properties than the UK and the US models and the
      differences in these EQ-5D scores had a small impact on ICUR, we recommended that
      for both clinical and policy purposes the Japan scheme should be used in Thai
      people. However, more research needs to be done.

PMID- 18811936
TI  - Exon creation and establishment in human genes.
AB  - BACKGROUND: A large proportion of species-specific exons are alternatively
      spliced. In primates, Alu elements play a crucial role in the process of exon
      creation but many new exons have appeared through other mechanisms. Despite many
      recent studies, it is still unclear which are the splicing regulatory
      requirements for de novo exonization and how splicing regulation changes
      throughout an exon's lifespan. RESULTS: Using comparative genomics, we have
      defined sets of exons with different evolutionary ages. Younger exons have weaker
      splice-sites and lower absolute values for the relative abundance of putative
      splicing regulators between exonic and adjacent intronic regions, indicating a
      less consolidated splicing regulation. This relative abundance is shown to
      increase with exon age, leading to higher exon inclusion. We show that this local
      difference in the density of regulators might be of biological significance, as
      it outperforms other measures in real exon versus pseudo-exon classification. We
      apply this new measure to the specific case of the exonization of anti-sense Alu
      elements and show that they are characterized by a general lack of exonic
      splicing silencers. CONCLUSIONS: Our results suggest that specific sequence
      environments are required for exonization and that these can change with time. We
      propose a model of exon creation and establishment in human genes, in which
      splicing decisions depend on the relative local abundance of regulatory motifs.
      Using this model, we provide further explanation as to why Alu elements serve as
      a major substrate for exon creation in primates. Finally, we discuss the benefits
      of integrating such information in gene prediction.

PMID- 18811937
TI  - Trunk asymmetry in juveniles.
AB  - BACKGROUND: Trunk asymmetry (TA) is a common phenomenon in children, but its
      incidence in juveniles is not known. The present cross sectional study reports TA
      in normal juveniles and provides data which describe the evolution of TA from
      early childhood to adolescence. MATERIALS AND METHODS: The scoliometer readings
      in both standing and sitting forward bending position (FBP) of 3301 children,
      (1645 boys, and 1656 girls) aged from 3 to 9 years old were studied. TA was
      quantified by measuring angle of trunk rotation (ATR) and children were
      categorized as symmetric (ATR = 0 degrees ), mild asymmetric (ATR 1 degrees - 6
      degrees ) and severely asymmetric (ATR >/= 7 degrees ). The difference of TA
      between standing and sitting FBP as well as differences between boys and girls in
      frequency of TA were also calculated. The scoliometer readings were analyzed by
      age to reveal at which age the juvenile pattern of TA changes into the adolescent
      one. RESULTS: 74.2% of boys and 77% of girls were symmetric (ATR = 0 degrees ) in
      the thoracic region in standing FBP, while 82.7% of boys and 84.1% of girls were
      symmetric in the thoracic region in sitting FBP. Juvenile girls are more
      symmetric than boys but severe TA was found almost the same between the two
      genders. A significant reduction in the frequency of mild TA from standing into
      sitting FBP, in all the examined regions in both boys and girls was found, but in
      severe TA this reduction is very small. Analysing scoliometer readings by age it
      appears that significant TA changes take place between 8-9 years of age for boys
      and between 6-7 and 8-9 years for girls. TA in boys is changing into the
      adolescent pattern at a later age than in girls. CONCLUSION: Juveniles were found
      more symmetric than adolescents, who were studied previously in a different
      study. Furthermore, juvenile girls were found more symmetric than boys. Juvenile
      TA pattern seems to be in accordance with the higher incidence of juvenile
      idiopathic scoliosis in boys. Furthermore, severe TA, which could be correlated
      with a scoliotic curve, was found to be more common to the left side. The present
      report provides information about the variability of back morphology in normal
      juveniles. The amount of TA in children is the indicator for referral and further
      orthopaedic assessment if a spinal curve is detected, but can also be used as a
      baseline for further research on idiopathic scoliosis aetiology.

PMID- 18811938
TI  - MalVac: database of malarial vaccine candidates.
AB  - BACKGROUND: The sequencing of genomes of the Plasmodium species causing malaria,
      offers immense opportunities to aid in the development of new therapeutics and
      vaccine candidates through Bioinformatics tools and resources. METHODS: The
      starting point of MalVac database is the collection of known vaccine candidates
      and a set of predicted vaccine candidates identified from the whole proteome
      sequences of Plasmodium species provided by PlasmoDb 5.4 release (31st October
      2007). These predicted vaccine candidates are the adhesins and adhesin-like
      proteins from Plasmodium species, Plasmodium falciparum, Plasmodium vivax and
      Plasmodium yoelii. Subsequently, these protein sequences were analysed through 20
      publicly available algorithms to obtain Orthologs, Paralogs, BetaWraps, TargetP,
      TMHMM, SignalP, CDDSearch, BLAST with Human Ref. Proteins, T-cell epitopes, B
      cell epitopes, Discotopes, and allergen predictions. All of this information was
      collected and organized with the ORFids of the protein sequences as primary keys.
      This information is relevant from the view point of Reverse Vaccinology in
      facilitating decision making on the most probable choice for vaccine strategy.
      RESULTS: Detailed information on the patterning of the epitopes and other motifs
      of importance from the viewpoint of reverse vaccinology has been obtained on the
      most probable protein candidates for vaccine investigation from three major
      malarial species. Analysis data are available on 161 adhesin proteins from P.
      falciparum, 137 adhesin proteins from P. vivax and 34 adhesin proteins from P.
      yoelii. The results are displayed in convenient tabular format and a facility to
      export the entire data has been provided. The MalVac database is a "community
      resource". Users are encouraged to export data and further contribute by value
      addition. Value added data may be sent back to the community either through
      MalVac or PlasmoDB. CONCLUSION: A web server MalVac for facilitation of the
      identification of probable vaccine candidates has been developed and can be
      freely accessed.

PMID- 18811939
TI  - Identification of transcripts involved in meiosis and follicle formation during
      ovine ovary development.
AB  - BACKGROUND: The key steps in germ cell survival during ovarian development are
      the entry into meiosis of oogonies and the formation of primordial follicles,
      which then determine the reproductive lifespan of the ovary. In sheep, these
      steps occur during fetal life, between 55 and 80 days of gestation, respectively.
      The aim of this study was to identify differentially expressed ovarian genes
      during prophase I meiosis and early folliculogenesis in sheep. RESULTS: In order
      to elucidate the molecular events associated with early ovarian differentiation,
      we generated two ovary stage-specific subtracted cDNA libraries using SSH. Large
      scale sequencing of these SSH libraries identified 6,080 ESTs representing 2,535
      contigs. Clustering and assembly of these ESTs resulted in a total of 2,101
      unique sequences depicted in 1,305 singleton (62.11%) and 796 contigs (37.9%)
      ESTs (clusters). BLASTX evaluation indicated that 99% of the ESTs were homologous
      to various known genes/proteins in a broad range of organisms, especially ovine,
      bovine and human species. The remaining 1% which exhibited any homology to known
      gene sequences was considered as novel. Detailed study of the expression patterns
      of some of these genes using RT-PCR revealed new promising candidates for ovary
      differentiation genes in sheep. CONCLUSION: We showed that the SSH approach was
      relevant to determining new mammalian genes which might be involved in oogenesis
      and early follicle development, and enabled the discovery of new potential oocyte
      and granulosa cell markers for future studies. These genes may have significant
      implications regarding our understanding of ovarian function in molecular terms,
      and for the development of innovative strategies to both promote and control
      fertility.

PMID- 18811940
TI  - Structural and functional divergence of two fish aquaporin-1 water channels
      following teleost-specific gene duplication.
AB  - BACKGROUND: Teleost radiation in the oceans required specific physiological
      adaptations in eggs and early embryos to survive in the hyper-osmotic seawater.
      Investigating the evolution of aquaporins (AQPs) in these vertebrates should help
      to elucidate how mechanisms for water homeostasis evolved. The marine teleost
      gilthead sea bream (Sparus aurata) has a mammalian aquaporin-1 (AQP1)-related
      channel, termed AQP1o, with a specialized physiological role in mediating egg
      hydration. However, teleosts have an additional AQP isoform structurally more
      similar to AQP1, though its relationship with AQP1o is unclear. RESULTS: By using
      phylogenetic and genomic analyses we show here that teleosts, unlike tetrapods,
      have two closely linked AQP1 paralogous genes, termed aqp1a and aqp1b (formerly
      AQP1o). In marine teleosts that produce hydrated eggs, aqp1b is highly expressed
      in the ovary, whereas in freshwater species that produce non-hydrated eggs, aqp1b
      has a completely different expression pattern or is not found in the genome. Both
      Aqp1a and Aqp1b are functional water-selective channels when expressed in Xenopus
      laevis oocytes. However, expression of chimeric and mutated proteins in oocytes
      revealed that the sea bream Aqp1b C-terminus, unlike that of Aqp1a, contains
      specific residues involved in the control of Aqp1b intracellular trafficking
      through phosphorylation-independent and -dependent mechanisms. CONCLUSION: We
      propose that 1) Aqp1a and Aqp1b are encoded by distinct genes that probably
      originated specifically in the teleost lineage by duplication of a common
      ancestor soon after divergence from tetrapods, 2) Aqp1b possibly represents a
      neofunctionalized AQP adapted to oocytes of marine and catadromous teleosts,
      thereby contributing to a water reservoir in eggs and early embryos that
      increases their survival in the ocean, and 3) Aqp1b independently acquired
      regulatory domains in the cytoplasmatic C-terminal tail for the specific control
      of Aqp1b expression in the plasma membrane.

PMID- 18811941
TI  - HECTAR: a method to predict subcellular targeting in heterokonts.
AB  - BACKGROUND: The heterokonts are a particularly interesting group of eukaryotic
      organisms; they include many key species of planktonic and coastal algae and
      several important pathogens. To understand the biology of these organisms, it is
      necessary to be able to predict the subcellular localisation of their proteins
      but this is not straightforward, particularly in photosynthetic heterokonts which
      possess a complex chloroplast, acquired as the result of a secondary
      endosymbiosis. This is because the bipartite target peptides that deliver
      proteins to these chloroplasts can be easily confused with the signal peptides of
      secreted proteins, causing currently available algorithms to make erroneous
      predictions. HECTAR, a subcellular targeting prediction method which takes into
      account the specific properties of heterokont proteins, has been developed to
      address this problem. RESULTS: HECTAR is a statistical prediction method designed
      to assign proteins to five different categories of subcellular targeting: Signal
      peptides, type II signal anchors, chloroplast transit peptides, mitochondrion
      transit peptides and proteins which do not possess any N-terminal target peptide.
      The recognition rate of HECTAR is 96.3%, with Matthews correlation coefficients
      ranging from 0.67 to 0.95. The method is based on a hierarchical architecture
      which implements the divide and conquer approach to identify the different
      possible target peptides one at a time. At each node of the hierarchy, the most
      relevant outputs of various existing subcellular prediction methods are combined
      by a Support Vector Machine. CONCLUSION: The HECTAR method is able to predict the
      subcellular localisation of heterokont proteins with high accuracy. It also
      efficiently predicts the subcellular localisation of proteins from cryptophytes,
      a group that is phylogenetically close to the heterokonts. A variant of HECTAR,
      called HECTARSEC, can be used to identify signal peptide and type II signal
      anchor sequences in proteins from any eukaryotic organism. Both HECTAR and
      HECTARSEC are available as a web application at the following address:
      http://www.sb-roscoff.fr/hectar/.

PMID- 18811942
TI  - Phospholipase A2 regulation of bovine endometrial (BEND) cell prostaglandin
      production.
AB  - BACKGROUND: Prostaglandins (PG), produced by the uterine endometrium, are key
      regulators of several reproductive events, including estrous cyclicity,
      implantation, pregnancy maintenance and parturition. Phospholipase A2 (PLA2)
      catalyzes the release of arachidonic acid from membrane phospholipids, the rate
      limiting step in PG biosynthesis. The bovine endometrial (BEND) cell line has
      served as a model system for investigating regulation of signaling mechanisms
      involved in uterine PG production but information concerning the specific PLA2
      enzymes involved and their role in regulation of this process is limited. The
      objectives of this investigation were to evaluate the expression and activities
      of calcium-dependent group IVA (PLA2G4A) and calcium-independent group VI
      (PLA2G6) enzymes in the regulation of BEND cell PG production. METHODS: Cells
      were grown to near-confluence and treated with phorbol 12, 13 dibutyrate (PDBu),
      interferon-tau (IFNT), the PLA2G4A inhibitor pyrrolidine-1 (PYR-1), the PLA2G6
      inhibitor bromoenol lactone (BEL) and combinations of each. Concentrations of
      PGF2alpha and PGE2 released into the medium were determined. Western blot
      analysis was performed on cellular protein to determine effects of treatment on
      expression of PLA2G4A, PLA2G6 and PLA2G4C. PLA2 assays were performed on intact
      cells by measuring arachidonic acid and linoleic acid release and group-specific
      PLA2 activity assays were performed on cell lysates. RESULTS: BEND cells produced
      about 10-fold more PGE2 than PGF2alpha under resting conditions. Production of
      both PGs increased significantly in response to PDBu-stimulation. PYR-1
      significantly diminished production of both PGs by resting cells and abolished
      the stimulatory effect of PDBu. BEL stimulated production of both PGs. IFNT
      reduced both PGE2 and PGF2alpha production by resting cells and diminished PDBu
      stimulation of PG production. Conversely, IFNT did not significantly reduce BEL
      stimulation of PG production. Cellular expression of PLA2G4A was enhanced by PDBu
      and this response was diminished by IFNT. Expression of PLA2G6 was not observed
      to be affected by treatments and no PLA2G4C expression was observed. Arachidonic
      acid release from intact cells was significantly increased by PDBu and this
      effect was attenuated by PYR-1 but not by BEL. Release of linoleic acid from
      intact cells was stimulated by PDBu and inhibited by BEL but not PYR-1. Group
      specific PLA2-activity assays demonstrated both PLA2G4A and PLA2G6 activity.
      CONCLUSION: Results from this study demonstrate that PGE2 and PGF2-alpha
      production by BEND cells is mediated by the activity and expression of PLA2G4A.
      Interferon-tau treatment diminished expression of PLA2G4A and PG production. BEND
      cells were shown to express PLA2G6 but, unlike primary or early passage luminal
      bovine endometrial cells, stimulation of PLA2G6 activity was not associated with
      increased PG production.

PMID- 18811943
TI  - Analysis of porcine transcriptional response to Salmonella enterica serovar
      Choleraesuis suggests novel targets of NFkappaB are activated in the mesenteric
      lymph node.
AB  - BACKGROUND: Specific knowledge of the molecular pathways controlling host
      pathogen interactions can increase our understanding of immune response biology
      as well as provide targets for drug development and genetic improvement of
      disease resistance. Toward this end, we have characterized the porcine
      transcriptional response to Salmonella enterica serovar Choleraesuis (S.
      Choleraesuis), a Salmonella serovar that predominately colonizes swine, yet can
      cause serious infections in human patients. Affymetrix technology was used to
      screen for differentially expressed genes in pig mesenteric lymph nodes (MLN)
      responding to infection with S. Choleraesuis at acute (8 hours (h), 24 h and 48 h
      post-inoculation (pi)) and chronic stages (21 days (d) pi). RESULTS: Analysis of
      variance with false discovery rate control identified 1,853 genes with
      significant changes in expression level (p-value < 0.01, q-value < 0.26, and fold
      change (FC) > 2) during infection as compared to un-inoculated control pigs. Down
      regulation of translation-related genes at 8 hpi and 24 hpi implied that S.
      Choleraesuis repressed host protein translation. Genes involved in the Th1,
      innate immune/inflammation response and apoptosis pathways were induced
      significantly. However, antigen presentation/dendritic cell (DC) function
      pathways were not affected significantly during infection. A strong NFkappaB
      dependent response was observed, as 58 known NFkappaB target genes were induced
      at 8, 24 and/or 48 hpi. Quantitative-PCR analyses confirmed the microarray data
      for 21 of 22 genes tested. Based on expression patterns, these target genes can
      be classified as an "Early" group (induced at either 8 or 24 hpi) and a "Late"
      group (induced only at 48 hpi). Cytokine activity or chemokine activity were
      enriched within the Early group genes GO annotations, while the Late group was
      predominantly composed of signal transduction and cell metabolism annotated
      genes. Regulatory motif analysis of the human orthologous promoters for both
      Early and Late genes revealed that 241 gene promoters were predicted to contain
      NFkappaB binding sites, and that of these, 51 Early and 145 Late genes were
      previously not known to be NFkappaB targets. CONCLUSION: Our study provides novel
      genome-wide transcriptional profiling data on the porcine response to S.
      Choleraesuis and expands the understanding of NFkappaB signaling in response to
      Salmonella infection. Comparison of the magnitude and timing of porcine MLN
      transcriptional response to different Salmonella serovars, S. Choleraesuis and S.
      Typhimurium, clearly showed a larger but later transcriptional response to S.
      Choleraesuis. Both microarray and QPCR data provided evidence of a strong
      NFkappaB-dependent host transcriptional response during S. Choleraesuis
      infection. Our data indicate that a lack of strong DC-mediated antigen
      presentation in the MLN may cause S. Choleraesuis infected pigs to develop a
      systemic infection, and our analysis predicts nearly 200 novel NFkappaB target
      genes which may be applicable across mammalian species.

PMID- 18811944
TI  - Myeloid dendritic cells display downregulation of C-type lectin receptors and
      aberrant lectin uptake in systemic lupus erythematosus.
AB  - INTRODUCTION: There is a growing body of evidence implicating aberrant dendritic
      cell function as a crucial component in the immunopathogenesis of systemic lupus
      erythematosus. The purpose of the present study was to characterize the
      phagocytic capacity and expression of receptors involved in pathogen recognition
      and self-nonself discrimination on myeloid dendritic cells from patients with
      lupus. METHODS: Unstimulated or stimulated monocyte-derived dendritic cells were
      obtained from lupus patients and healthy control individuals, and expression of C
      type lectin receptors (mannose receptor and dendritic cell-specific intercellular
      adhesion molecule-grabbing nonintegrin), complement-receptor 3 and Fc gamma
      receptors was determined by flow cytometry. Dextran uptake by lupus and control
      dendritic cells was also assessed by flow cytometry. Serum IFN gamma was
      quantified by ELISA, and uptake of microbial products was measured using
      fluorescently labeled zymosan. RESULTS: When compared with dendritic cells from
      healthy control individuals, unstimulated and stimulated lupus dendritic cells
      displayed significantly decreased dextran uptake and mannose receptor and
      dendritic cell-specific intercellular adhesion molecule-grabbing nonintegrin
      expression. Decreased expression of the mannose receptor was associated with high
      serum IFN gamma levels, but not with maturation status or medications. Diminished
      dextran uptake and mannose receptor expression correlated with lupus disease
      activity. There were no differences between control and lupus dendritic cells in
      the expression of other pattern recognition receptors or in the capacity to
      uptake zymosan particles CONCLUSIONS: Lupus dendritic cells have diminished
      endocytic capacity, which correlates with decreased mannose receptor expression.
      While this phenomenon appears primarily intrinsic to dendritic cells, modulation
      by serum factors such as IFN gamma could play a role. These abnormalities may be
      relevant to the aberrant immune homeostasis and the increased susceptibility to
      infections described in lupus.

PMID- 18811945
TI  - The Serine/threonine kinase Stk33 exhibits autophosphorylation and phosphorylates
      the intermediate filament protein Vimentin.
AB  - BACKGROUND: Colocalization of Stk33 with vimentin by double immunofluorescence in
      certain cells indicated that vimentin might be a target for phosphorylation by
      the novel kinase Stk33. We therefore tested in vitro the ability of Stk33 to
      phosphorylate recombinant full length vimentin and amino-terminal truncated
      versions thereof. In order to prove that Stk33 and vimentin are also in vivo
      associated proteins co-immunoprecipitation experiments were carried out. For
      testing the enzymatic activity of immunoprecipitated Stk33 we incubated
      precipitated Stk33 with recombinant vimentin proteins. To investigate whether
      Stk33 binds directly to vimentin, an in vitro co-sedimentation assay was
      performed. RESULTS: The results of the kinase assays demonstrate that Stk33 is
      able to specifically phosphorylate the non-alpha-helical amino-terminal domain of
      vimentin in vitro. Furthermore, co-immunoprecipitation experiments employing
      cultured cell extracts indicate that Stk33 and vimentin are associated in vivo.
      Immunoprecipitated Stk33 has enzymatic activity as shown by successful
      phosphorylation of recombinant vimentin proteins. The results of the co
      sedimentation assay suggest that vimentin binds directly to Stk33 and that no
      additional protein mediates the association. CONCLUSION: We hypothesize that
      Stk33 is involved in the in vivo dynamics of the intermediate filament
      cytoskeleton by phosphorylating vimentin.

PMID- 18811946
TI  - Comparison study on k-word statistical measures for protein: from sequence to
      'sequence space'.
AB  - BACKGROUND: Many proposed statistical measures can efficiently compare protein
      sequence to further infer protein structure, function and evolutionary
      information. They share the same idea of using k-word frequencies of protein
      sequences. Given a protein sequence, the information on its related protein
      sequences hasn't been used for protein sequence comparison until now. This paper
      proposed a scheme to construct protein 'sequence space' which was associated with
      protein sequences related to the given protein, and the performances of
      statistical measures were compared when they explored the information on protein
      'sequence space' or not. This paper also presented two statistical measures for
      protein: gre.k (generalized relative entropy) and gsm.k (gapped similarity
      measure). RESULTS: We tested statistical measures based on protein 'sequence
      space' or not with three data sets. This not only offers the systematic and
      quantitative experimental assessment of these statistical measures, but also
      naturally complements the available comparison of statistical measures based on
      protein sequence. Moreover, we compared our statistical measures with alignment
      based measures and the existing statistical measures. The experiments were
      grouped into two sets. The first one, performed via ROC (Receiver Operating
      Curve) analysis, aims at assessing the intrinsic ability of the statistical
      measures to discriminate and classify protein sequences. The second set of the
      experiments aims at assessing how well our measure does in phylogenetic analysis.
      Based on the experiments, several conclusions can be drawn and, from them, novel
      valuable guidelines for the use of protein 'sequence space' and statistical
      measures were obtained. CONCLUSION: Alignment-based measures have a clear
      advantage when the data is high redundant. The more efficient statistical measure
      is the novel gsm.k introduced by this article, the cos.k followed. When the data
      becomes less redundant, gre.k proposed by us achieves a better performance, but
      all the other measures perform poorly on classification tasks. Almost all the
      statistical measures achieve improvement by exploring the information on
      'sequence space' as word's length increases, especially for less redundant data.
      The reasonable results of phylogenetic analysis confirm that Gdis.k based on
      'sequence space' is a reliable measure for phylogenetic analysis. In summary, our
      quantitative analysis verifies that exploring the information on 'sequence space'
      is a promising way to improve the abilities of statistical measures for protein
      comparison.

PMID- 18811947
TI  - Spectrocolorimetric evaluation of repaired articular cartilage after a
      microfracture.
AB  - BACKGROUND: In clinical practice, surgeons differentiate color changes in
      repaired cartilage compared with surrounding intact cartilage, but cannot
      quantify these color changes. Objective assessments are required. A
      spectrocolorimeter was used to evaluate whether intact and repaired cartilage can
      be quantified. FINDINGS: We investigated the use of a spectrocolorimeter and the
      application of two color models (L* a* b* colorimetric system and spectral
      reflectance distribution) to describe and quantify articular cartilage. In this
      study, we measured the colors of intact and repaired cartilage after a
      microfracture. Histologically, the repaired cartilage was a mixture of
      fibrocartilage and hyaline cartilage. In the L* a* b* colorimetric system, the L*
      and a* values recovered to close to the values of intact cartilage, whereas the
      b* value decreased over time after the operation. Regarding the spectral
      reflectance distribution at 12 weeks after the operation, the repaired cartilage
      had a higher spectral reflectance ratio than intact cartilage between wavelengths
      of 400 to 470 nm. CONCLUSION: This study reports the first results regarding the
      relationship between spectrocolorimetric evaluation and the histological findings
      of repair cartilage after a microfracture. Our findings demonstrate the ability
      of spectrocolorimetric measurement to judge the repair cartilage after treatment
      on the basis of objective data such as the L*, a* and b* values and the SRP as a
      coincidence index of the spectral reflectance curve.

PMID- 18811948
TI  - Double primary bronchogenic carcinoma of the lung and papillary thyroid
      carcinoma: a case report.
AB  - INTRODUCTION: Double primary bronchogenic carcinoma and papillary carcinoma of
      the thyroid are extremely rare. We describe the case of a patient who underwent
      surgical resection for these two cancers. CASE PRESENTATION: A 56-year-old man
      presented to our hospital complaining of a cough with blood-tinged sputum. A
      slowly growing mass in the left lobe of the lung had been noted for about 1 year.
      He underwent video-assisted thoracic surgery of the left lower lobe and
      mediastinal lymph node dissection through an 8 cm utility incision. Pathology
      revealed a well-differentiated adenocarcinoma and the dissected lymph nodes were
      negative for malignancy. He also complained of a mass in his neck, which had
      grown slowly for over 5 years. A computed tomography scan of the neck revealed a
      left thyroid mass compressing the trachea towards the right side. There was no
      cervical lymphadenopathy. A left thyroid lobectomy was performed and pathology
      revealed a papillary carcinoma. Thus, he underwent a second operation to remove
      the right lobe of the thyroid. He underwent subsequent adjuvant chemotherapy.
      CONCLUSION: In a review of the literature, it appears that there has only been
      one previously reported case of these two cancers, which was in Japan. The
      relationship between these two cancers is still unclear, and more case reports
      are required to determine this relationship.

PMID- 18811949
TI  - Distinction of Plasmodium falciparum recrudescence and re-infection by MSP2
      genotyping: a caution about unstandardized classification criteria.
AB  - BACKGROUND: Plasmodium falciparum genotyping with molecular polymorphic markers
      is widely employed to distinguish recrudescence from re-infection in antimalarial
      drug efficacy monitoring programmes. However, limitations occur on agarose gel
      DNA measurements used to resolve the polymorphisms. Without empirical data, the
      current distinction of pre- and post-treatment bands, as persistent or new
      infection, is subjective and often varying by author. This study measures
      empirical tolerance limits for classifying different-sized bands as same or
      different alleles during MSP2 genotyping. METHODS: P. falciparum field samples
      from 161 volunteers were genotyped by nested PCR using polymorphic MSP2 family
      specific primers. Data were analysed to determine variability of band size
      measurements between identical MSP2 alleles randomized into different agarose
      lanes. RESULTS: The mean (95% CI) paired difference in band size between
      identical alleles was 9.8 bp (1.48 - 18.16 bp, p = 0.022) for 3D7/IC and 2.54 (
      3.04 - 8.05 bp, p = 0.362) for FC27. Based on these findings, pre- and post
      treatment samples with 3D7/IC alleles showing less than 18 bp difference
      corresponded to recrudescence, with 95% confidence, while greater difference
      indicated new infection. FC27 allele differences were much narrower. For both
      3D7/IC and FC27 amplicon, allele detection sensitivity was significantly higher
      with 13 mul compared to 20 mul or 30 mul lane loading volumes. CONCLUSION: During
      MSP genotyping, it is useful to standardize classifications against measurement
      of background variability on identical alleles, in order to obtain reliable
      findings. It is critical to use a fixed optimal lane loading volume for constant
      allele patency, to avoid the disappearance or false appearance of new infection.

PMID- 18811950
TI  - Broad ligament cystic lymphangioma: a case report.
AB  - INTRODUCTION: Cystic lymphangiomas are uncommon tumors that can arise from any
      part of the body. They can pose a diagnostic and therapeutic challenge. They are
      more common in infants and children than adults. Broad ligament cystic
      lymphangioma is extremely rare. CASE PRESENTATION: A 70-year-old multiparous
      woman presented with an abdominal mass of 20-year duration. A large cystic
      swelling was detected on computed tomography scan that was found to arise from
      the left adnexal region. This 19 kg lesion was found arising from the broad
      ligament. It was successfully removed. A detailed pathological study, including
      immunohistochemistry, was required to diagnose the lesion as a cystic
      lymphangioma. CONCLUSION: Lymphangiomas should be treated with total surgical
      excision. Broad ligament lymphangiomas are extremely rare but must be considered
      as a differential diagnosis of cystic lesions in that region.

PMID- 18811951
TI  - The rules of gene expression in plants: organ identity and gene body methylation
      are key factors for regulation of gene expression in Arabidopsis thaliana.
AB  - BACKGROUND: Microarray technology is a widely used approach for monitoring genome
      wide gene expression. For Arabidopsis, there are over 1,800 microarray
      hybridizations representing many different experimental conditions on Affymetrix
      ATH1 gene chips alone. This huge amount of data offers a unique opportunity to
      infer the principles that govern the regulation of gene expression in plants.
      RESULTS: We used bioinformatics methods to analyze publicly available data
      obtained using the ATH1 chip from Affymetrix. A total of 1887 ATH1 hybridizations
      were normalized and filtered to eliminate low-quality hybridizations. We
      classified and compared control and treatment hybridizations and determined
      differential gene expression. The largest differences in gene expression were
      observed when comparing samples obtained from different organs. On average, ten
      fold more genes were differentially expressed between organs as compared to any
      other experimental variable. We defined "gene responsiveness" as the number of
      comparisons in which a gene changed its expression significantly. We defined
      genes with the highest and lowest responsiveness levels as hypervariable and
      housekeeping genes, respectively. Remarkably, housekeeping genes were best
      distinguished from hypervariable genes by differences in methylation status in
      their transcribed regions. Moreover, methylation in the transcribed region was
      inversely correlated (R2 = 0.8) with gene responsiveness on a genome-wide scale.
      We provide an example of this negative relationship using genes encoding TCA
      cycle enzymes, by contrasting their regulatory responsiveness to nitrate and
      methylation status in their transcribed regions. CONCLUSION: Our results indicate
      that the Arabidopsis transcriptome is largely established during development and
      is comparatively stable when faced with external perturbations. We suggest a
      novel functional role for DNA methylation in the transcribed region as a key
      determinant capable of restraining the capacity of a gene to respond to
      internal/external cues. Our findings suggest a prominent role for epigenetic
      mechanisms in the regulation of gene expression in plants.

PMID- 18811952
TI  - Evolutionary rate and gene expression across different brain  regions.
AB  - BACKGROUND: The evolutionary rate of a protein is a basic measure of evolution at
      the molecular level. Previous studies have shown that genes expressed in the
      brain have significantly lower evolutionary rates than those expressed in somatic
      tissues. RESULTS: We study the evolutionary rates of genes expressed in 21
      different human brain regions. We find that genes highly expressed in the more
      recent cortical regions of the brain have lower evolutionary rates than genes
      highly expressed in subcortical regions. This may partially result from the
      observation that genes that are highly expressed in cortical regions tend to be
      highly expressed in subcortical regions, and thus their evolution faces a richer
      set of functional constraints. The frequency of mammal-specific and primate
      specific genes is higher in the highly expressed gene sets of subcortical brain
      regions than in those of cortical brain regions. The basic inverse correlation
      between evolutionary rate and gene expression is significantly stronger in brain
      versus nonbrain tissues, and in cortical versus subcortical regions. Extending
      upon this cortical/subcortical trend, this inverse correlation is generally more
      marked for tissues that are located higher along the cranial vertical axis during
      development, giving rise to the possibility that these tissues are also more
      evolutionarily recent. CONCLUSIONS: We find that cortically expressed genes are
      more conserved than subcortical ones, and that gene expression levels exert
      stronger constraints on sequence evolution in cortical versus subcortical
      regions. Taken together, these findings suggest that cortically expressed genes
      are under stronger selective pressure than subcortically expressed genes.

PMID- 18811953
TI  - Localization of the Carnation Italian ringspot virus replication protein p36 to
      the mitochondrial outer membrane is mediated by an internal targeting signal and
      the TOM complex.
AB  - BACKGROUND: Carnation Italian ringspot virus (CIRV) is a positive-strand RNA
      virus that causes massive structural alterations of mitochondria in infected host
      cells, the most conspicuous being the formation of numerous internal
      vesicles/spherules that are derived from the mitochondrial outer membrane and
      serve as the sites for viral RNA replication. While the membrane-bound components
      of the CIRV replication complex, including a 36-kD RNA-binding protein (p36), are
      known to be essential for these changes in mitochondrial morphology and are
      relatively well characterized in terms of their roles in nascent viral RNA
      synthesis, how these proteins are specifically targeted and inserted into
      mitochondria is poorly defined. RESULTS: Here we report on the molecular signal
      responsible for sorting p36 to the mitochondrial outer membrane. Using a
      combination of gain-of-function assays with portions of p36 fused to reporter
      proteins and domain-swapping assays with p36 and another closely-related viral
      RNA-binding protein, p33, that sorts specifically to the peroxisomal boundary
      membrane, we show that the mitochondrial targeting information in p36 resides
      within its two transmembrane domains (TMDs) and intervening hydrophilic loop
      sequence. Comprehensive mutational analysis of these regions in p36 revealed that
      the primary targeting determinants are the moderate hydrophobicity of both TMDs
      and the positively-charged face of an amphipathic helix within the intervening
      loop sequence. We show also using bimolecular fluorescence complementation (BiFC)
      that p36 interacts with certain components of the translocase complex in the
      mitochondrial outer membrane (TOM), but not with the sorting and assembly
      machinery (SAM). CONCLUSION: Our results provide insight to how viruses, such as
      CIRV, exploit specific host-cell protein sorting pathways to facilitate their
      replication. The characterization of the targeting and insertion of p36 into the
      mitochondrial outer membrane also sheds light on the mechanisms involved in
      sorting of host-cell membrane proteins to mitochondria, a process that has been
      largely unexplored in plants.

PMID- 18811954
TI  - Impact of different leaf velocities and dose rates on the number of monitor units
      and the dose-volume-histograms using intensity modulated radiotherapy with
      sliding-window technique.
AB  - BACKGROUND: Intensity modulated radiotherapy (IMRT) using sliding window
      technique utilises a leaf sequencing algorithm, which takes some control system
      limitations like dose rates (DR) and velocity of the leafs (LV) into account. The
      effect of altering these limitations on the number of monitor units and radiation
      dose to the organs at risk (OAR) were analysed. METHODS: IMRT plans for different
      LVs from 1.0 cm/sec to 10.0 cm/sec and different DRs from 100 MU/min to 600
      MU/min for two patients with prostate cancer and two patients with squamous cell
      cancer of the scalp (SCCscalp) were calculated using the same "optimal fluence
      map". For each field the number of monitor units, the dose volume histograms and
      the differences in the "actual fluence maps" of the fields were analysed.
      RESULTS: With increase of the DR and decrease of the LV the number of monitor
      units increased and consequentially the radiation dose given to the OAR. In
      particular the serial OARs of patients with SCCscalp, which are located outside
      the end position of the leafs and inside the open field, received an additional
      dose of a higher DR and lower LV is used. CONCLUSION: For best protection of
      organs at risk, a low DR and high LV should be applied. But the consequence of a
      low DR is both a long treatment time and also that a LV of higher than 3.0 cm/sec
      is mechanically not applicable. Our recommendation for an optimisation of the
      discussed parameters is a leaf velocity of 2.5 cm/sec and a dose rate of 300-400
      MU/min (prostate cancer) and 100-200 MU/min (SCCscalp) for best protection of
      organs at risk, short treatment time and number of monitor units.

PMID- 18811955
TI  - Distinct roles of Shh and Fgf signaling in regulating cell proliferation during
      zebrafish pectoral fin development.
AB  - BACKGROUND: Cell proliferation in multicellular organisms must be coordinated
      with pattern formation. The major signaling pathways directing pattern formation
      in the vertebrate limb are well characterized, and we have therefore chosen this
      organ to examine the interaction between proliferation and patterning. Two
      important signals for limb development are members of the Hedgehog (Hh) and
      Fibroblast Growth Factor (Fgf) families of secreted signaling proteins. Sonic
      hedgehog (Shh) directs pattern formation along the anterior/posterior axis of the
      limb, whereas several Fgfs in combination direct pattern formation along the
      proximal/distal axis of the limb. RESULTS: We used the genetic and
      pharmacological amenability of the zebrafish model system to dissect the relative
      importance of Shh and Fgf signaling in regulating proliferation during
      development of the pectoral fin buds. In zebrafish mutants disrupting the shh
      gene, proliferation in the pectoral fin buds is initially normal, but later is
      strongly reduced. Correlating with this reduction, Fgf signaling is normal at
      early stages, but is later lost in shh mutants. Furthermore, pharmacological
      inhibition of Hh signaling for short periods has little effect on either Fgf
      signaling, or on expression of G1- and S-phase cell-cycle genes, whereas long
      periods of inhibition lead to the downregulation of both. In contrast, even short
      periods of pharmacological inhibition of Fgf signaling lead to strong disruption
      of proliferation in the fin buds, without affecting Shh signaling. To directly
      test the ability of Fgf signaling to regulate proliferation in the absence of Shh
      signaling, we implanted beads soaked with Fgf protein into shh mutant fin buds.
      We find that Fgf-soaked beads rescue proliferation in the pectoral find buds of
      shh mutants, indicating that Fgf signaling is sufficient to direct proliferation
      in zebrafish fin buds in the absence of Shh. CONCLUSION: Previous studies have
      shown that both Shh and Fgf signaling are crucial for outgrowth of the vertebrate
      limb. The results presented here show that the role of Shh in this process is
      indirect, and is mediated by its effect on Fgf signaling. By contrast, the
      activity of the Fgf pathway affects proliferation directly and independently of
      its effect on Shh. These results show that Fgf signaling is of primary importance
      in directing outgrowth of the limb bud, and clarify the role of the Shh-Fgf
      feedback loop in regulating proliferation.

PMID- 18811956
TI  - HSV-tk/GCV gene therapy mediated by EBV-LMP1 for EBV-associated cancer.
AB  - BACKGROUND: To investigate the feasibility of gene therapy in treating Epstein
      Barr virus (EBV)-associated cancer by employing the suicide gene, herpes simplex
      virus thymidine kinase/ganciclovir (HSV-tk/GCV), which uses the signaling pathway
      through the HIV-long terminal repeat (LTR) gene which is expressed from a nuclear
      factor-kappaB (NF-kappaB)-binding motif-containing promoter that is regulated by
      EBV-latent membrane protein 1 (LMP1) via NF-kappaB. METHODS: First, we
      constructed the plasmid pVLTR-tk, which was regulated by EBV-LMP1 via NF-kappaB,
      and then investigated the cytotoxic effect of the pVLTR-tk/GCV on cancer cells,
      using MTT assays, clonogenic assays, flow cytometry, and animal experiments.
      RESULTS: The activation of TK was increased after transfection of the pVLTR-tk
      into the EBV-LMP1 positive cells. After GCV treatment, the clonogenicity and
      survival of the cells substantially declined, and a bystander effect was also
      observed. The LMP1 positive cells exhibited remarkable apoptosis following pVLTR
      tk/GCV treatment, and the pVLTR-tk/GCV restrained tumor growth in vivo for EBV
      LMP1 positive cancers. CONCLUSION: The pVLTR-tk/GCV suicide gene system may be
      used as a new gene targeting strategy for EBV-associated cancer.

PMID- 18811957
TI  - Maternal risk factors for abnormal placental growth: the national collaborative
      perinatal project.
AB  - BACKGROUND: Previous studies of maternal risk factors for abnormal placental
      growth have focused on placental weight and placental ratio as measures of
      placental growth. We sought to identify maternal risk factors for placental
      weight and two neglected dimensions of placental growth: placental thickness and
      chorionic plate area. METHODS: We conducted an analysis of 24,135 mother-placenta
      pairs enrolled in the National Collaborative Perinatal Project, a prospective
      cohort study of pregnancy and child health. We defined growth restriction as <
      10th percentile and hypertrophy as > 90th percentile for three placental growth
      dimensions: placental weight, placental thickness and chorionic plate area. We
      constructed parallel multinomial logistic regression analyses to identify (a)
      predictors of restricted growth (vs. normal) and (b) predictors of hypertrophic
      growth (vs. normal). RESULTS: Black race was associated with an increased
      likelihood of growth restriction for placental weight, thickness and chorionic
      plate area, but was associated with a reduced likelihood of hypertrophy for these
      three placental growth dimensions. We observed an increased likelihood of growth
      restriction for placental weight and chorionic plate area among mothers with
      hypertensive disease at 24 weeks or beyond. Anemia was associated with a reduced
      likelihood of growth restriction for placental weight and chorionic plate area.
      Pre-pregnancy BMI and pregnancy weight gain were associated with a reduced
      likelihood of growth restriction and an increased likelihood of hypertrophy for
      all three dimensions of placental growth. CONCLUSION: Maternal risk factors are
      either associated with placental growth restriction or placental hypertrophy not
      both. Our findings suggest that the placenta may have compensatory responses to
      certain maternal risk factors suggesting different underlying biological
      mechanisms.

PMID- 18811958
TI  - Longitudinal population-based studies of affective disorders: where to from here?
AB  - BACKGROUND: Longitudinal, population-based, research is important if we are to
      better characterize the lifetime patterns and determinants of affective
      disorders. While studies of this type are becoming increasingly prevalent, there
      has been little discussion about the limitations of the methods commonly used.
      METHODS: Discussion paper including a brief review of key prospective population
      based studies as the basis for a critical appraisal of current approaches.
      RESULTS: We identified a number of common methodological weaknesses that restrict
      the potential of longitudinal research to characterize the diversity, prognosis,
      and determinants of affective disorders over time. Most studies using
      comprehensive diagnostic instruments have either been of relatively brief
      duration, or have suffered from long periods between waves. Most etiologic
      research has focused on first onset diagnoses, although these may be relatively
      uncommon after early adulthood and the burden of mental disorders falls more
      heavily on individuals with recurring disorders. Analysis has tended to be based
      on changes in diagnostic status rather than anges in symptom levels, limiting
      study power. Diagnoses have generally been treated as homogeneous entities and
      few studies have explored whether diagnostic subtypes such as atypical depression
      vary in their etiology or prognosis. Little research has considered whether there
      are distinct trajectories of symptoms over time and most has focused on
      individual disorders such as depression, rather than considering the relationship
      over time between symptoms of different affective disorders. There has also been
      limited longitudinal research on factors in the physical or social environment
      that may influence the onset, recurrence or chronicity of symptoms. CONCLUSION:
      Many important, and in some respects quite basic, questions remain about the
      trajectory of depression and anxiety disorders over the life course and the
      factors that influence their incidence, recurrence and prognosis. Innovative
      approaches that consider symptoms of all affective disorders, and how these
      change over time, has the potential to greatly increase our understanding of the
      heterogeneity of these important conditions and of the individual and
      environmental characteristics that influence their life course. Using
      longitudinal research to define sub classes of affective disorders may also be of
      great benefit for studies seeking to define the genetic determinants of
      susceptibility to these conditions.

PMID- 18811959
TI  - Simultaneous occurrence of cerebellar medulloblastoma and pituitary adenoma: A
      case report.
AB  - PURPOSE: We present the unusual occurrence of two distinct neoplasms in a 42-year
      old woman with an operated pituitary adenoma 18 years ago. METHODS: Clinical
      history, magnetic resonance imaging studies and histopathological findings were
      utilized for our diagnostic considerations. RESULTS: Concomitant presence of a
      cerebellar medulloblastoma secondary disseminated within the spinal canal and a
      pituitary macroadenoma, was identified. CONCLUSION: To the best of our knowledge,
      this is the first reported case in which these two neoplasms are simultaneously
      occurred in the same individual. A short review of the literature is performed.

PMID- 18811960
TI  - Tissue specific promoters improve specificity of AAV9 mediated transgene
      expression following intra-vascular gene delivery in neonatal mice.
AB  - The AAV9 capsid displays a high natural affinity for the heart following a single
      intravenous (IV) administration in both newborn and adult mice. It also results
      in substantial albeit relatively lower expression levels in many other tissues.
      To increase the overall safety of this gene delivery method we sought to identify
      which one of a group of promoters is able to confer the highest level of cardiac
      specific expression and concurrently, which is able to provide a broad
      biodistribution of expression across both cardiac and skeletal muscle. The in
      vivo behavior of five different promoters was compared: CMV, desmin (Des), alpha
      myosin heavy chain (alpha-MHC), myosin light chain 2 (MLC-2) and cardiac troponin
      C (cTnC). Following IV administration to newborn mice, LacZ expression was
      measured by enzyme activity assays. Results showed that rAAV2/9-mediated gene
      delivery using the alpha-MHC promoter is effective for focal transgene expression
      in the heart and the Des promoter is highly suitable for achieving gene
      expression in cardiac and skeletal muscle following systemic vector
      administration. Importantly, these promoters provide an added layer of control
      over transgene activity following systemic gene delivery.

PMID- 18811961
TI  - Role of viral hemagglutinin glycosylation in anti-influenza activities of
      recombinant surfactant protein D.
AB  - BACKGROUND: Surfactant protein D (SP-D) plays an important role in innate defense
      against influenza A viruses (IAVs) and other pathogens. METHODS: We tested
      antiviral activities of recombinant human SP-D against a panel of IAV strains
      that vary in glycosylation sites on their hemagglutinin (HA). For these
      experiments a recombinant version of human SP-D of the Met11, Ala160 genotype was
      used after it was characterized biochemically and structurally. RESULTS:
      Oligosaccharides at amino acid 165 on the HA in the H3N2 subtype and 104 in the
      H1N1 subtype are absent in collectin-resistant strains developed in vitro and are
      important for mediating antiviral activity of SP-D; however, other glycans on the
      HA of these viral subtypes also are involved in inhibition by SP-D. H3N2 strains
      obtained shortly after introduction into the human population were largely
      resistant to SP-D, despite having the glycan at 165. H3N2 strains have become
      steadily more sensitive to SP-D over time in the human population, in association
      with addition of other glycans to the head region of the HA. In contrast, H1N1
      strains were most sensitive in the 1970s-1980s and more recent strains have
      become less sensitive, despite retaining the glycan at 104. Two H5N1 strains were
      also resistant to inhibition by SP-D. By comparing sites of glycan attachment on
      sensitive vs. resistant strains, specific glycan sites on the head domain of the
      HA are implicated as important for inhibition by SP-D. Molecular modeling of the
      glycan attachment sites on HA and the carbohydrate recognition domain of SPD are
      consistent with these observations. CONCLUSION: Inhibition by SP-D correlates
      with presence of several glycan attachment sites on the HA. Pandemic and avian
      strains appear to lack susceptibility to SP-D and this could be a contributory
      factor to their virulence.

PMID- 18811963
TI  - Tetany caused by chronic diarrhea in a child with celiac disease: A case report.
AB  - There is no awareness about celiac disease (CD) in Mexico. A 2.9 year old
      mestizo boy was admitted to a Mexican hospital with muscle cramps and fine
      tremors. He suffered chronic diarrhea, abdominal distention, hypotrophic limbs,
      stunting and wasting, and presented hypocalcemia, anemia and high titers of
      serological markers. Diagnosis of CD was confirmed by a duodenal biopsy. After
      replacement of calcium and a gluten-free diet, the symptoms resolved within 6
      weeks. After 2-months, serum analyses, anthropometric data as well as antibodies
      titers were normal after 4 years. CD screening tests are needed in chronic
      diarrhea for any ethnicity patients.

PMID- 18811962
TI  - Overlapping functions of the starch synthases SSII and SSIII in amylopectin
      biosynthesis in Arabidopsis.
AB  - BACKGROUND: The biochemical mechanisms that determine the molecular architecture
      of amylopectin are central in plant biology because they allow long-term storage
      of reduced carbon. Amylopectin structure imparts the ability to form semi
      crystalline starch granules, which in turn provides its glucose storage function.
      The enzymatic steps of amylopectin biosynthesis resemble those of the soluble
      polymer glycogen, however, the reasons for amylopectin's architectural
      distinctions are not clearly understood. The multiplicity of starch biosynthetic
      enzymes conserved in plants likely is involved. For example, amylopectin chain
      elongation in plants involves five conserved classes of starch synthase (SS),
      whereas glycogen biosynthesis typically requires only one class of glycogen
      synthase. RESULTS: Null mutations were characterized in AtSS2, which codes for
      SSII, and mutant lines were compared to lines lacking SSIII and to an Atss2,
      Atss3 double mutant. Loss of SSII did not affect growth rate or starch quantity,
      but caused increased amylose/amylopectin ratio, increased total amylose, and
      deficiency in amylopectin chains with degree of polymerization (DP) 12 to DP28.
      In contrast, loss of both SSII and SSIII caused slower plant growth and
      dramatically reduced starch content. Extreme deficiency in DP12 to DP28 chains
      occurred in the double mutant, far more severe than the summed changes in SSII-
      or SSIII-deficient plants lacking only one of the two enzymes. CONCLUSION: SSII
      and SSIII have partially redundant functions in determination of amylopectin
      structure, and these roles cannot be substituted by any other conserved SS,
      specifically SSI, GBSSI, or SSIV. Even though SSIII is not required for the
      normal abundance of glucan chains of DP12 to DP18, the enzyme clearly is capable
      of functioning in production such chains. The role of SSIII in producing these
      chains cannot be detected simply by analysis of an individual mutation.
      Competition between different SSs for binding to substrate could in part explain
      the specific distribution of glucan chains within amylopectin.

PMID- 18811964
TI  - NF-kappaB mediates the survival of human bronchial epithelial cells exposed to
      cigarette smoke extract.
AB  - BACKGROUND: We have previously reported that low concentrations of cigarette
      smoke extract induce DNA damage without leading to apoptosis or necrosis in human
      bronchial epithelial cells (HBECs), and that IL-6/STAT3 signaling contributes to
      the cell survival. Since NF-kappaB is also involved in regulating apoptosis and
      cell survival, the current study was designed to investigate the role of NF
      kappaB in mediating cell survival in response to cigarette smoke exposure in
      HBECs. METHODS: Both the pharmacologic inhibitor of NF-kappaB, curcumin, and RNA
      interference targeting p65 were used to block NF-kappaB signaling in HBECs.
      Apoptosis and cell survival were then assessed by various methods including COMET
      assay, LIVE/DEAD Cytotoxicity/Viability assay and colony formation assay.
      RESULTS: Cigarette smoke extract (CSE) caused DNA damage and cell cycle arrest in
      S phase without leading to apoptosis in HBECs as evidenced by TUNEL assay, COMET
      assay and DNA content assay. CSE stimulated NF-kappaB -DNA binding activity and
      up-regulated Bcl-XL protein in HBECs. Inhibition of NF-kappaB by the
      pharmacologic inhibitor curcumin (20 microM) or suppression of p65 by siRNA
      resulted in a significant increase in cell death in response to cigarette smoke
      exposure. Furthermore, cells lacking p65 were incapable of forming cellular
      colonies when these cells were exposed to CSE, while they behaved normally in the
      regular culture medium. CONCLUSION: The current study demonstrates that CSE
      activates NF-kappaB and up-regulates Bcl-XL through NF-kB activation in HBECs,
      and that CSE induces cell death in cells lacking p65. These results suggest that
      activation of NF-kappaB regulates cell survival following DNA damage by cigarette
      smoke in human bronchial epithelial cells.

PMID- 18811965
TI  - Separation of Hepatitis C genotype 4a into IgG-depleted and IgG-enriched
      fractions reveals a unique quasispecies profile.
AB  - BACKGROUND: Hepatitis C virus (HCV) circulates in an infected individual as a
      heterogeneous mixture of closely related viruses called quasispecies. The E1/E2
      region of the HCV genome is hypervariable (HVR1) and is targeted by the humoral
      immune system. Hepatitis C virions are found in two forms: antibody associated or
      antibody free. The objective of this study was to investigate if separation of
      Hepatitis C virions into antibody enriched and antibody depleted fractions
      segregates quasispecies populations into distinctive swarms. RESULTS: A HCV
      genotype 4a specimen was fractionated into IgG-depleted and IgG-enriched
      fractions by use of Albumin/IgG depletion spin column. Clonal analysis of these
      two fractions was performed and then compared to an unfractionated sample.
      Following sequence analysis it was evident that the antibody depleted fraction
      was significantly more heterogeneous than the antibody enriched fraction,
      revealing a unique quasispecies profile. An in-frame 3 nt insertion was observed
      in 26% of clones in the unfractionated population and in 64% of clones in the IgG
      depleted fraction. In addition, an in-frame 3 nt indel event was observed in 10%
      of clones in the unfractionated population and in 9% of clones in the IgG
      depleted fraction. Neither of these latter events, which are rare occurrences in
      genotype 4a, was identified in the IgG-enriched fraction. CONCLUSION: In
      conclusion, the homogeneity of the IgG-enriched species is postulated to
      represent a sequence that was strongly recognised by the humoral immune system at
      the time the sample was obtained. The heterogeneous nature of the IgG-depleted
      fraction is discussed in the context of humoral escape.

PMID- 18811966
TI  - Childhood sarcoidosis: A rare but fascinating disorder.
AB  - Childhood sarcoidosis is a rare multisystemic granulomatous disorder of unknown
      etiology. In the pediatric series reported from the southeastern United States,
      sarcoidosis had a higher incidence among African Americans. Most reported
      childhood cases have occurred in patients aged 13-15 years. Macrophages bearing
      an increased expression of major histocompatibility class (MHC) II molecules most
      likely initiate the inflammatory response of sarcoidosis by presenting an
      unidentified antigen to CD4+ Th (helper-inducer) lymphocytes. A persistent,
      poorly degradable antigen driven cell-mediated immune response leads to a
      cytokine cascade, to granuloma formation, and eventually to fibrosis. Frequently
      observed immunologic features include depression of cutaneous delayed-type
      hypersensitivity and a heightened helper T cell type 1 (Th1) immune response at
      sites of disease. Circulating immune complexes, along with signs of B cell
      hyperactivity, may also be found. The clinical presentation can vary greatly
      depending upon the organs involved and age of the patient. Two distinct forms of
      sarcoidosis exist in children. Older children usually present with a multisystem
      disease similar to the adult manifestations, with frequent hilar lymphadenopathy
      and pulmonary infiltrations. Early-onset sarcoidosis is a unique form of the
      disease characterized by the triad of rash, uveitis, and arthritis in children
      presenting before four years of age. The diagnosis of sarcoidosis is confirmed by
      demonstrating a typical noncaseating granuloma on a biopsy specimen. Other
      granulmatous diseases should be reasonably excluded. The current therapy of
      choice for sarcoidosis in children with multisystem involvement is oral
      corticosteroids. Methotrexate given orally in low doses has been effective, safe
      and steroid sparing in some patients. Alternative immunosuppressive agents, such
      as azathioprine, cyclophosphamide, chlorambucil, and cyclosporine, have been
      tried in adult cases of sarcoidosis with questionable efficacy. The high toxicity
      profile of these agents, including an increased risk of lymphoproliferative
      disorders and carcinomas, has limited their use to patients with severe disease
      refractory to other agents. Successful steroid sparing treatment with
      mycophenolate mofetil was described in an adolescent with renal-limited
      sarcoidosis complicated by renal failure. Novel treatment strategies for
      sarcoidosis have been developed including the use of TNF-alpha inhibitors, such
      as infliximab. The long-term course and prognosis is not well established in
      childhood sarcoidosis, but it appears to be poorer in early-onset disease.

PMID- 18811967
TI  - Passive administration of monoclonal antibodies to anthrolysin O prolong survival
      in mice lethally infected with Bacillus anthracis.
AB  - BACKGROUND: Bacillus anthracis has two major virulence factors: a tripartite
      toxin that produces lethal and edema toxins and a polyglutamic acid capsule. A
      recent report suggested that a toxin belonging to the cholesterol dependent
      cytolysin (CDC) family, anthrolysin O (ALO) was a new virulence factor for B.
      anthracis but subsequent studies have questioned its relevance in pathogenesis.
      In this study, we examined the immunogenicity of recombinant anthrolysin O (rALO)
      in mice. RESULTS: BALB/c mice immunized with rALO and boosted after two weeks,
      produce sera with strong Ab responses with a predominance of IgG1 and IgG2a. Five
      hybridomas to rALO were recovered representing the IgM, IgG1, and IgG2b isotypes.
      Passive administration of 3 of the five monoclonal antibodies (mAbs) to rALO
      prior to infection with lethal intravenous (i.v.) B. anthracis Sterne strain
      infection in mice was associated with enhanced average survival and a greater
      likelihood of surviving infection. A combination of two mAbs to ALO was more
      effective than either mAb separately. One mAb (64F8) slowed the toxicity of rALO
      for J774.16 macrophage-like cells. CONCLUSION: Our results suggest that ALO
      contributes to the virulence of B. anthracis Sterne strain in this infection
      model and that Ab response to ALO may contribute to protection in certain
      circumstances.

PMID- 18811968
TI  - The spatial distribution of leprosy in four villages in Bangladesh: an
      observational study.
AB  - BACKGROUND: There is a higher case-detection rate for leprosy among spatially
      proximate contacts such as household members and neighbors. Spatial information
      regarding the clustering of leprosy can be used to improve intervention
      strategies. Identifying high-risk areas within villages around known cases can be
      helpful in finding new cases. METHODS: Using geographic information systems, we
      created digital maps of four villages in a highly endemic area in northwest
      Bangladesh. The villages were surveyed three times over four years. The spatial
      pattern of the compounds--a small group of houses--was analyzed, and we looked
      for spatial clusters of leprosy cases. RESULTS: The four villages had a total
      population of 4,123. There were 14 previously treated patients and we identified
      19 new leprosy patients during the observation period. However, we found no
      spatial clusters with a probability significantly different from the null
      hypothesis of random occurrence. CONCLUSION: Spatial analysis at the microlevel
      of villages in highly endemic areas does not appear to be useful for identifying
      clusters of patients. The search for clustering should be extended to a higher
      aggregation level, such as the subdistrict or regional level. Additionally, in
      highly endemic areas, it appears to be more effective to target complete villages
      for contact tracing, rather than narrowly defined contact groups such as
      households.

PMID- 18811969
TI  - Microbial Diagnostic Array Workstation (MDAW): a web server for diagnostic array
      data storage, sharing and analysis.
AB  - BACKGROUND: Microarrays are becoming a very popular tool for microbial detection
      and diagnostics. Although these diagnostic arrays are much simpler when compared
      to the traditional transcriptome arrays, due to the high throughput nature of the
      arrays, the data analysis requirements still form a bottle neck for the
      widespread use of these diagnostic arrays. Hence we developed a new online data
      sharing and analysis environment customised for diagnostic arrays. METHODS:
      Microbial Diagnostic Array Workstation (MDAW) is a database driven application
      designed in MS Access and front end designed in ASP.NET. CONCLUSION: MDAW is a
      new resource that is customised for the data analysis requirements for microbial
      diagnostic arrays.

PMID- 18811970
TI  - Cessation of deliberate self harm following eye movement desensitisation and
      reprocessing: A case report.
AB  - We present a case report of an eighteen year old female patient presenting with
      a psychological trauma related complaint. Part of the manifestation of the
      complaint included acts of self cutting over a number of years. Following two
      sessions of Eye Movement Desensitization & Reprocessing with one of the authors
      (DM) her self cutting ceased. This is maintained at thirteen months follow up. We
      conclude that Eye Movement Desensitization & Reprocessing may be an effective
      treatment option in reducing repeat self harm where traumatic events are noted to
      be the precursor to deliberate self harm.

PMID- 18811971
TI  - The spatial distribution of leprosy cases during 15 years of a leprosy control
      program in Bangladesh: an observational study.
AB  - BACKGROUND: An uneven spatial distribution of leprosy can be caused by the
      influence of geography on the distribution of risk factors over the area, or by
      population characteristics that are heterogeneously distributed over the area. We
      studied the distribution of leprosy cases detected by a control program to
      identify spatial and spatio-temporal patterns of occurrence and to search for
      environmental risk factors for leprosy. METHODS: The houses of 11,060 leprosy
      cases registered in the control area during a 15-year period (1989-2003) were
      traced back, added to a geographic database (GIS), and plotted on digital maps.
      We looked for clusters of cases in space and time. Furthermore, relationships
      with the proximity to geographic features, such as town center, roads, rivers,
      and clinics, were studied. RESULTS: Several spatio-temporal clusters were
      observed for voluntarily reported cases. The cases within and outside clusters
      did not differ in age at detection, percentage with multibacillary leprosy, or
      sex ratio. There was no indication of the spread from one point to other parts of
      the district, indicating a spatially stable endemic situation during the study
      period. The overall risk of leprosy in the district was not associated with
      roads, rivers, and leprosy clinics. The risk was highest within 1 kilometer of
      town centers and decreased with distance from town centers. CONCLUSION: The
      association of a risk of leprosy with the proximity to towns indicates that rural
      towns may play an important role in the epidemiology of leprosy in this district.
      Further research on the role of towns, particularly in rural areas, is warranted.

PMID- 18811972
TI  - Structural analysis of FAD synthetase from Corynebacterium ammoniagenes.
AB  - BACKGROUND: The prokaryotic FAD synthetase family - a group of bifunctional
      enzymes that catalyse riboflavin phosphorylation and FMN adenylylation within a
      single polypeptide chain- was analysed in terms of sequence and structure.
      RESULTS: Sequences of nearly 800 prokaryotic species were aligned. Those related
      with bifunctional FAD synthetase activities showed conservation of several
      consensus regions and highly conserved residues. A 3D model for the FAD
      synthetase from Corynebacterium ammoniagenes (CaFADS) was generated. This model
      confirms that the N-terminal and C-terminal domains are related to
      nucleotydyltransferases and riboflavin kinases, respectively. Models for the
      interaction of CaFADS with its substrates were also produced, allowing location
      of all the protein substrates in their putative binding pockets. These include
      two independent flavin binding sites for each CaFADS activity. CONCLUSION: For
      the first time, the putative presence of a flavin binding site for the
      adenylylation activity, independent from that related with the phosphorylation
      activity, is shown. Additionally, these models suggest the functional relevance
      of some residues putatively involved in the catalytic processes. Their relevant
      roles were analysed by site-directed mutagenesis. A role was confirmed for H28,
      H31, S164 and T165 in the stabilisation of the P groups and the adenine moiety of
      ATP and, the P of FMN for the adenylylation. Similarly, T208, N210 and E268
      appear critical for accommodation of the P groups of ATP and the ribityl end of
      RF in the active site for the phosphorylation process. Finally, the C-terminal
      domain was shown to catalyse the phosphorylation process on its own, but no
      reaction at all was observed with the individually expressed N-terminal domain.

PMID- 18811973
TI  - Non-healing painful ulcers in a patient with chronic kidney disease and role of
      sodium thiosulfate: a case report.
AB  - INTRODUCTION: Calciphylaxis is a rare but dreadful complication of chronic kidney
      disease. It is characterized by nodular subcutaneous calcification and painful
      tissue necrosis which often results in ulceration and secondary infection,
      leading to a high rate of mortality. Pathogenesis of this disease is not well
      understood and there are very few, poorly studied treatment options for this
      disease. CASE PRESENTATION: We report a case of 60 year old Caucasian female with
      history of long standing diabetes and chronic kidney disease stage 5 who
      presented with a very high calcium phosphorous product, markedly elevated intact
      PTH levels and X-ray changes consistent with diagnosis of calciphylaxis. Patient
      was initially managed by parathyroidectomy and later on was also treated with
      intravenous sodium thiosulfate thrice weekly with each hemodialysis session for
      duration of 10 weeks. CONCLUSION: Patient had rapid and dramatic relief of her
      symptoms of pain. Treatment with sodium thiosulfate was well tolerated without
      any side effects, accompanied by significant symptomatic relief but without any
      effect on disease progression. So the role of sodium thiosulfate in calciphylaxis
      is unknown and need further studies.

PMID- 18811974
TI  - Percutaneous transluminal angioplasty in the treatment of stenosis of
      arteriovenous fistulae for hemodialysis.
AB  - BACKGROUND: Thrombosis following stenosis of arteriovenous fistulae resulting in
      the loss of vascular access for hemodialysis is an important complication in
      patients with chronic renal failure. Percutaneous transluminal angioplasty is
      being used more frequently in the treatment of stenosis aiming at increasing the
      patency of arteriovenous fistulae. OBJECTIVE: To evaluate the primary patency of
      arteriovenous fistulae following percutaneous transluminal angioplasty. PATIENTS
      AND METHOD: Patients submitted to percutaneous transluminal angioplasty in the
      Angiology service of Hospital de Base in 2004 were analyzed over an average
      follow-up of 10 months (2 to 16 months). RESULTS: A total of 22 angioplasties
      were performed in 20 fistulae of 19 patients. Of the 19 patients, one did not
      complete follow-up and one presented with a rupture of the fistulae. The
      following complications occurred in the remaining 18 fistulae, three deaths with
      two fistulae patent until death; one exeresis of prosthesis due to infection (53
      days after the procedure); two thromboses (3 and 49 days after the procedure) and
      four restenosis (3 were submitted to a second angioplasty and one treated
      surgically). At the end of the follow-up, 11 fistulae (55%) were patent and with
      a flow rate in hemodialysis > 300 mL/min. Primary patency was 82.4% over three
      months; 81.2% over six months; 54.5% over 9 months and 50% over 1 year.
      CONCLUSION: Percutaneous transluminal angioplasty is an efficacious method for
      the correction of stenosis of arteriovenous fistulae for hemodialysis, prolonging
      the patency of the fistula and enabling new interventions.

PMID- 18811975
TI  - Identifying gene regulatory modules of heat shock response in yeast.
AB  - BACKGROUND: A gene regulatory module (GRM) is a set of genes that is regulated by
      the same set of transcription factors (TFs). By organizing the genome into GRMs,
      a living cell can coordinate the activities of many genes in response to various
      internal and external stimuli. Therefore, identifying GRMs is helpful for
      understanding gene regulation. RESULTS: Integrating transcription factor binding
      site (TFBS), mutant, ChIP-chip, and heat shock time series gene expression data,
      we develop a method, called Heat-Inducible Module Identification Algorithm
      (HIMIA), for reconstructing GRMs of yeast heat shock response. Unlike previous
      module inference tools which are static statistics-based methods, HIMIA is a
      dynamic system model-based method that utilizes the dynamic nature of time series
      gene expression data. HIMIA identifies 29 GRMs, which in total contain 182 heat
      inducible genes regulated by 12 heat-responsive TFs. Using various types of
      published data, we validate the biological relevance of the identified GRMs. Our
      analysis suggests that different combinations of a fairly small number of heat
      responsive TFs regulate a large number of genes involved in heat shock response
      and that there may exist crosstalk between heat shock response and other cellular
      processes. Using HIMIA, we identify 68 uncharacterized genes that may be involved
      in heat shock response and we also identify their plausible heat-responsive
      regulators. Furthermore, HIMIA is capable of assigning the regulatory roles of
      the TFs that regulate GRMs and Cst6, Hsf1, Msn2, Msn4, and Yap1 are found to be
      activators of several GRMs. In addition, HIMIA refines two clusters of genes
      involved in heat shock response and provides a better understanding of how the
      complex expression program of heat shock response is regulated. Finally, we show
      that HIMIA outperforms four current module inference tools (GRAM, MOFA,
      ReMoDisvovery, and SAMBA), and we conduct two randomization tests to show that
      the output of HIMIA is statistically meaningful. CONCLUSION: HIMIA is effective
      for reconstructing GRMs of yeast heat shock response. Indeed, many of the
      reconstructed GRMs are in agreement with previous studies. Further, HIMIA
      predicts several interesting new modules and novel TF combinations. Our study
      shows that integrating multiple types of data is a powerful approach to studying
      complex biological systems.

PMID- 18811976
TI  - Association between regular participation in sports and leisure time behaviors in
      Brazilian adolescents: a cross-sectional study.
AB  - BACKGROUND: The belief that adolescents engaged in sports increase their overall
      physical activity level while simultaneously decreasing physical inactivity has
      been the foundation of many intervention programs in developing countries. The
      aim of this study was to analyze the association between regular participation in
      sports and both active behaviors and TV viewing during leisure time. METHODS: A
      total of 1752 Brazilian adolescents (812 = male and 940 = female) participated in
      this study. Regular participation in sports, as well as active behaviors
      (exemplified by walking or cycling) and TV viewing during leisure time were
      assessed by means of a questionnaire. The chi-square test analyzed the
      association between sports practice and leisure time behaviors, and the Poisson
      regression with robust variance indicated the magnitude of these associations.
      RESULTS: The prevalence of regular participation in sports was 14.8% (95%
      confidence interval 13.2% to 16.5%). After adjustment for all confounders,
      participation in sports was associated with, at the highest frequency, cycling
      (PR = 2.55 [1.80-3.60]) and walking (PR = 2.69 [1.98-3.64]) during leisure time.
      However, there was not an association between the participation in sports and
      frequency of TV viewing (PR = 1.28 [0.81-2.02]). CONCLUSION: This study presented
      data indicating that the regular participation in sports is positively associated
      with a higher frequency of physically active behaviors during leisure time.
      However, the results did not support the hypothesis that the engagement in sports
      necessarily decreases leisure time spent in TV viewing.

PMID- 18811977
TI  - Reliability and accuracy of interview data in non-smoking female lung cancer case
      control study.
AB  - BACKGROUND: Valid interview data is critical to the final results of the study.
      The purpose of this study was to investigate the reliability of epidemiological
      data obtained in non-smoking female lung cancer case-control study in China.
      METHODS: Fifty-six pairs of cases and controls, 10% percent of all the collected
      subjects were re-interviewed by three interviewers who underwent identical
      standardized training. A limited number of questions included in the original
      survey were asked again, the responses from the re-interview were compared with
      the original interview. Kappa was calculated by negative rates of agreement,
      positive rates of agreement and total rates of agreement to the accordance degree
      between the two interviews. RESULTS: The Kappa values were all more than 0.5 in
      all the studied indexes. The Kappa values descended from 0.92 in family history
      of cancer to 0.56 in oral contraception use. Errors in collecting and classifying
      data did occur, and were especially common for complicated clinical events, such
      as a drug exposure occurring many years before. CONCLUSION: We identified four
      sources of this variability, three in collecting the data, and one in coding. As
      a result of these findings, strategies are proposed for improving the quality of
      interview data obtained in epidemiological research. Before finding a good
      solution, the strategy of data collecting and coding should be simple and easy to
      inspect.

PMID- 18811978
TI  - Implementation of Integrated Learning Program in neurosciences during first year
      of traditional medical course: perception of students and faculty.
AB  - BACKGROUND: Our college introduced an integrated learning program (ILP) for first
      year undergraduates with an aim to develop, implement and evaluate a module for
      CNS in basic sciences and to assess the feasibility of an ILP in phase I of
      medical education in a college following traditional medical curriculum. METHODS:
      The idea of implementing ILP for Central Nervous System (CNS) in phase one was
      conceived by curriculum development committee drawn from faculty of all phases.
      After a series of meetings of curriculum development committee, inputs from basic
      science and clinical departments, a time table was constructed. Various teaching
      learning methods, themes for integrated didactic lectures, case based learning
      and clinical exposure were decided. Basic science faculty were made to
      participate actively in both case based learning and hospital visits along with
      clinical experts. The completed program was evaluated based on structured
      questionnaire. RESULTS: Sixty percent students rated the program good to
      excellent with reference to appreciation, understanding and application of basic
      science knowledge in health and disease. Seventy eight percent felt that this
      program will help them perform better in later days of clinical training. However
      sixty percent students felt that ILP will not help them perform better at the
      first professional examination. Seventy two per cent of faculty agreed that this
      program improved understanding and application of basic science knowledge of
      students. Ninety percent of faculty felt that this program will help them perform
      better in later days of clinical training. CONCLUSION: The adoption of present
      integrated module for CNS and the use of multiple teaching learning methods have
      been proven to be useful in acquisition of knowledge from the student
      satisfaction point of view. Students and faculty expressed an overall
      satisfaction towards ILP for CNS. The study showed that it is possible to adopt
      an integrated learning module in the first year of medical course under a
      conventional curriculum.

PMID- 18811979
TI  - GBNet: deciphering regulatory rules in the co-regulated genes using a Gibbs
      sampler enhanced Bayesian network approach.
AB  - BACKGROUND: Combinatorial regulation of transcription factors (TFs) is important
      in determining the complex gene expression patterns particularly in higher
      organisms. Deciphering regulatory rules between cooperative TFs is a critical
      step towards understanding the mechanisms of combinatorial regulation. RESULTS:
      We present here a Bayesian network approach called GBNet to search for DNA motifs
      that may be cooperative in transcriptional regulation and the sequence
      constraints that these motifs may satisfy. We showed that GBNet outperformed the
      other available methods in the simulated and the yeast data. We also demonstrated
      the usefulness of GBNet on learning regulatory rules between YY1, a human TF, and
      its co-factors. Most of the rules learned by GBNet on YY1 and co-factors were
      supported by literature. In addition, a spacing constraint between YY1 and E2F
      was also supported by independent TF binding experiments. CONCLUSION: We thus
      conclude that GBNet is a useful tool for deciphering the "grammar" of
      transcriptional regulation.

PMID- 18811980
TI  - SCUD: Saccharomyces cerevisiae ubiquitination database.
AB  - BACKGROUND: Ubiquitination is an important post-translational modification
      involved in diverse biological processes. Therefore, genomewide representation of
      the ubiquitination system for a species is important. DESCRIPTION: SCUD is a web
      based database for the ubiquitination system in Saccharomyces cerevisiae (Baker's
      yeast). We first searched for all the known enzymes involved in the
      ubiquitination process in yeast, including E1, E2, E3, and deubiquitination
      enzymes. Then, ubiquitinated substrates were collected by literature search.
      Especially, E3 and deubiquitination enzymes are classified into classes and
      subclasses by their shared domains and unique functions. As a result, 42
      different E3 enzymes were grouped into corresponding classes and subclasses, and
      940 ubiquitinated substrates including mutant substrates were identified. All the
      enzyme and substrate information are interconnected by hyperlinks, which makes it
      easy to view the enzyme-specific ubiquitination information. CONCLUSION: This
      database aims to represent a comprehensive yeast ubiquitination system, and is
      easily expandable with the further experimental data. We expect that this
      database will be useful for the research on the ubiquitination systems of other
      higher organisms. SCUD is accessible at http://scud.kaist.ac.kr.

PMID- 18811981
TI  - Sp1 is involved in H2O2-induced PUMA gene expression and apoptosis in colorectal
      cancer cells.
AB  - BACKGROUND: Reactive oxygen species (ROS) are intricately involved in tumor
      progression through effects on proliferation, apoptosis and metastasis. But how
      ROS works is not well understood. In previous study, we found PUMA (p53
      upregulated modulator of apoptosis) played an important role in oxaliplatin
      induced apoptosis. In the present study, we detect the role of PUMA in H2O2
      induced apoptosis in colorectal cancer cells and investigate the potential
      mechanism. METHODS AND RESULTS: We showed that H2O2 stimulated the activity of a
      493 PUMA promoter reporter gene construct. Suppressing the expression of PUMA
      abrogated H2O2-induced apoptosis. Deletion of the Sp1-binding sites also
      decreased the transactivation of PUMA promoter by H2O2. Furthermore, induction of
      PUMA promoter activity by H2O2 was abrogated by PFT-alpha (a p53 inhibitor) and
      Mithramycin A (a Sp1 inhibitor), as compared with PFT-alpha alone. To determine
      the effects of Sp1 on PUMA in H2O2-induced apoptosis, procaspase 3, procaspase 9
      and procaspase 8 expression was assessed. Mithramycin A and PFT-alpha also
      reduced H2O2-induced apoptosis synergistically and abrogated the expression of
      procaspase 3 and procaspase 9. CONCLUSION: Our findings suggest that PUMA plays a
      role in H2O2-induced apoptosis, and that Sp1 works together with p53 in the
      regulation of H2O2-induced PUMA expression and apoptosis in colorectal cancer
      cells. This study provides important regulatory insights in the mechanisms of ROS
      in colorectal cancer.

PMID- 18811982
TI  - The role of polyclonal intravenous immunoglobulin in treating HIV-infected
      children with severe bacterial infections: a retrospective cohort study.
AB  - BACKGROUND: Mortality among HIV-infected children in developing countries remains
      high after serious bacterial infections despite the use of antibiotics.
      Intravenous immunoglobulin (IVIG) has been used as an adjuvant therapy to treat
      these infections, but little data exists regarding its efficacy, and previous
      studies have focused on IVIG as a prophylactic agent. We examined the impact of
      IVIG as an adjuvant therapy in reducing mortality and length of hospital stay in
      HIV-infected children with serious bacterial infections. METHODS: This
      retrospective study focused on pediatric admissions at a large urban hospital
      between 2002 and 2006. Children between the ages of one month and nine years of
      age with laboratory confirmed HIV-status, serious bacterial infection, no prior
      exposure to IVIG, and a hospital length of stay of 5 days or more, were eligible
      for inclusion. RESULTS: A total of 140 children (median age 1.2 years) met
      inclusion criteria; lower respiratory tract infection was diagnosed in 94 (67%)
      of the children, while 74 (53%) had bacterial sepsis. Fifty-four (39%) children
      were receiving antiretroviral therapy and 39 (28%) were receiving tuberculosis
      treatment. Overall 73 (52%) were treated with IVIG, with the majority (74%) of
      children receiving a single dose. Thirteen (9%) died during their hospital
      admission. In crude analysis IVIG was significantly associated with increased
      mortality was (Odds Ratio (OR): 5.8; 95% Confidence Interval (CI): 1.2-27.1) and
      this association was weakened by adjustment for other predictors of mortality (OR
      4.3, 95% CI 0.7-27.9, p = 0.123). IVIG use was also associated with longer
      hospital stays. CONCLUSION: Administration of one to three doses of IVIG during
      the acute phase of illness does not appear to reduce mortality or the length of
      hospital stays in HIV-infected children with serious bacterial infections.
      However, the retrospective nature of this study makes confounding by indication
      difficult to control and further studies regarding the timing, dosing, and method
      of administration are required. Nonetheless the routine use of IVIG in resource
      limited settings should be carefully considered given its high cost.

PMID- 18811983
TI  - Gene expression subtraction of non-cancerous lung from smokers and non-smokers
      with adenocarcinoma, as a predictor for smokers developing lung cancer.
AB  - BACKGROUND: Lung cancer is the commonest cause of cancer death in developed
      countries. Adenocarcinoma is becoming the most common form of lung cancer.
      Cigarette smoking is the main risk factor for lung cancer. Long-term cigarettes
      smoking may be characterized by genetic alteration and diffuse injury of the
      airways surface, named field cancerization, while cancer in non-smokers is
      usually clonally derived. Detecting specific genes expression changes in non
      cancerous lung in smokers with adenocarcinoma may give us instrument for
      predicting smokers who are going to develop this malignancy. OBJECTIVES: We
      described the gene expression in non-cancerous lungs from 21 smoker patients with
      lung adenocarcinoma and compare it to gene expression in non-cancerous lung
      tissue from 10 non-smokers with primary lung adenocarcinoma. METHODS: Total RNA
      was isolated from peripheral non-cancerous lung tissue. The cDNA was hybridized
      to the U133A GeneChip array. Hierarchical clustering analysis on genes obtained
      from smokers and non-smokers, after subtracting were exported to the Ingenuity
      Pathway Analysis software for further analysis. RESULTS: The genes subtraction
      resulted in disclosure of 36 genes with high score. They were subsequently mapped
      and sorted based on location, cellular components, and biochemical activity. The
      gene functional analysis disclosed 20 genes, which are involved in cancer process
      (P = 7.05E-5 to 2.92E-2). CONCLUSION: Detected genes may serve as a predictor for
      smokers who may be at high risk of developing lung cancer. In addition, since
      these genes originating from non-cancerous lung, which is the major area of the
      lungs, a sample from an induced sputum may represent it.

PMID- 18811984
TI  - Different gene-expression profiles for the poorly differentiated carcinoma and
      the highly differentiated papillary adenocarcinoma in mammary glands support
      distinct metabolic pathways.
AB  - BACKGROUND: Deregulation of Stat5 in the mammary gland of transgenic mice causes
      tumorigenesis. Poorly differentiated carcinoma and highly differentiated
      papillary adenocarcinoma tumors evolve. To distinguish the genes and elucidate
      the cellular processes and metabolic pathways utilized to preserve these
      phenotypes, gene-expression profiles were analyzed. METHODS: Mammary tumors were
      excised from transgenic mice carrying a constitutively active variant of Stat5,
      or a Stat5 variant lacking s transactivation domain. These tumors displayed
      either the carcinoma or the papillary adenocarcinoma phenotypes. cRNAs, prepared
      from each tumor were hybridized to an Affymetrix GeneChip(R) Mouse Genome 430A
      2.0 array. Gene-ontology analysis, hierarchical clustering and biological-pathway
      analysis were performed to distinct the two types of tumors. Histopathology and
      immunofluorescence staining complemented the comparison between the tumor
      phenotypes. RESULTS: The nucleus-cytoskeleton-plasma membrane axis is a major
      target for differential gene expression between phenotypes. In the carcinoma,
      stronger expression of genes coding for specific integrins, cytoskeletal proteins
      and calcium-binding proteins highlight cell-adhesion and motility features of the
      tumor cells. This is supported by the higher expression of genes involved in O
      glycan synthesis, TGF-beta, activin, their receptors and Smad3, as well as the
      Notch ligands and members of the gamma-secretase complex that enable Notch
      nuclear localization. The Wnt pathway was also a target for differential gene
      expression. Higher expression of genes encoding the degradation complex of the
      canonical pathway and limited TCF expression in the papillary adenocarcinoma
      result in membranal accumulation of beta-catenin, in contrast to its nuclear
      translocation in the carcinoma. Genes involved in cell-cycle arrest at G1 and
      response to DNA damage were more highly expressed in the papillary
      adenocarcinomas, as opposed to favored G2/M regulation in the carcinoma tumors.
      CONCLUSION: At least six metabolic pathways support the morphological and
      functional differences between carcinomas and papillary adenocarcinomas.
      Differential gene-expression profiles favor cell adhesion, motility and
      proliferation in the carcinoma. Cell-cell contact, polarity, earlier cell-cycle
      arrest and DNA damage control are better displayed in the papillary
      adenocarcinoma.

PMID- 18811985
TI  - Mucus on the move: embed it or expel it--the patient, the clinician, and now the
      ventilator.

PMID- 18811986
TI  - Extending the use of inhaled anesthetics beyond the operating room: a giant snake
      creeping into the intensive care unit.

PMID- 18811987
TI  - Wheeze detection in the pediatric intensive care unit.

PMID- 18811988
TI  - Consumer health care information on the internet: does the public benefit?

PMID- 18811989
TI  - Ventilation patterns influence airway secretion movement.
AB  - BACKGROUND: Retention of airway secretions is a common and serious problem in
      ventilated patients. Treating or avoiding secretion retention with mucus
      thinning, patient-positioning, airway suctioning, or chest or airway vibration or
      percussion may provide short-term benefit. METHODS: In a series of laboratory
      experiments with a test-lung system we examined the role of ventilator settings
      and lung-impedance on secretion retention and expulsion. Known quantities of a
      synthetic dye-stained mucus simulant with clinically relevant properties were
      injected into a transparent tube the diameter of an adult trachea and exposed to
      various mechanical-ventilation conditions. Mucus-simulant movement was measured
      with a photodensitometric technique and examined with image-analysis software. We
      tested 2 mucus-simulant viscosities and various peak flows,
      inspiratory/expiratory flow ratios, intrinsic positive end-expiratory pressures,
      ventilation waveforms, and impedance values. RESULTS: Ventilator settings that
      produced flow bias had a major effect on mucus movement. Expiratory flow bias
      associated with intrinsic positive end-expiratory pressure generated by elevated
      minute ventilation moved mucus toward the airway opening, whereas intrinsic
      positive end-expiratory pressure generated by increased airway resistance moved
      the mucus toward the lungs. Inter-lung transfer of mucus simulant occurred
      rapidly across the "carinal divider" between interconnected test lungs set to
      radically different compliances; the mucus moved out of the low-compliance lung
      and into the high-compliance lung. CONCLUSIONS: The movement of mucus simulant
      was influenced by the ventilation pattern and lung impedance. Flow bias obtained
      with ventilator settings may clear or embed mucus during mechanical ventilation.

PMID- 18811990
TI  - Feasibility and potential cost/benefit of routine isoflurane sedation using an
      anesthetic-conserving device: a prospective observational study.
AB  - BACKGROUND: Inhaled sedation is efficient and easily controllable; in low
      concentrations it causes minimal changes in the patient and very little
      interference with hemodynamics. Awakening after inhaled sedation is quick and
      predictable. The major reason inhaled sedation has not become widely used in
      intensive care is that no commercially available administration device has been
      available. METHODS: In our intensive care unit we conducted a prospective
      observational study to assess the feasibility, benefits, and costs of routine
      isoflurane sedation via the AnaConDa anesthetic-administration device. We
      included 15 adult patients who required > 24 hours of deep sedation. Conventional
      intravenous sedation (benzodiazepine and opioid) had been administered according
      to a sedation protocol that included a predetermined target Ramsay-scale sedation
      score. We then switched to inhaled isoflurane via the AnaConDa, and measured
      sedation efficacy, cumulative dose, and daily cost of sedation. Adverse events
      were prospectively defined and monitored. RESULTS: The sedation goal was reached
      with isoflurane in all 15 patients (P < .01, compared to the conventional
      sedation protocol). Hemodynamic changes were nonsignificant, and no renal or
      hepatic dysfunctions were observed. The frequency of meeting the sedation goal
      was significantly better with isoflurane than with our usual sedation protocol.
      With isoflurane, awakening from sedation was always <or= 4 hours, despite some
      long-duration sedations (up to 14.5 d). The overall daily cost of the 2 sedation
      protocols was not different in the whole group of 15 patients, but in the
      subgroup of 7 patients who required a mean midazolam infusion larger than the
      average dose, the cost difference was very significant (euro218 +/- 111 vs
      euro110 +/- 19, P < .01). CONCLUSIONS: Routine ICU isoflurane sedation with the
      AnaConDa is easily feasible, effective, safe, and has a relatively short
      awakening period. In some patients with sedation difficulties, this sedation
      method may significantly decrease sedation cost and enhance sedation efficacy.

PMID- 18811991
TI  - Wheeze detection in the pediatric intensive care unit: comparison among
      physician, nurses, respiratory therapists, and a computerized respiratory sound
      monitor.
AB  - OBJECTIVE: To correlate wheeze detection in the pediatric intensive care unit
      among staff members (a physician, nurses, and respiratory therapists [RTs]) and
      digital recordings from a computerized respiratory sound monitor (PulmoTrack).
      METHODS: We prospectively studied 11 patients in the pediatric intensive care
      unit. A physician, nurses, and RTs auscultated the patients and recorded their
      opinions about the presence of wheeze at baseline and then every hour for 6
      hours. The clinician auscultated while the PulmoTrack recorded the lung sounds.
      The data were analyzed by a technician trained in interpretation of acoustic data
      and by a panel of experts blinded to the source of the recorded data, who scored
      all tracks for the presence or absence of wheeze. The degree of correlation among
      the expert panel, the staff, and the PulmoTrack was evaluated with the Kappa
      coefficient and McNemar's test. The determinations of the expert panel were taken
      as the true state (accepted standard). RESULTS: The PulmoTrack and expert panel
      were in agreement on detection of wheeze during inspiration, expiration, and the
      whole breath cycle; in all cases the Kappa coefficients were 0.54, 0.42, and 0.50
      respectively. The PulmoTrack was significantly more sensitive than the physician
      (P = .002), nurses (P < .001), or RTs (P = .001). However, the specificity of the
      PulmoTrack was not significantly different from that of the physician, nurses, or
      RTs. CONCLUSIONS: Between the physician, RTs, and nurses there was agreement
      about the presence of wheeze in critically ill patients in the pediatric
      intensive care unit. Compared to the objective acoustic measurements from the
      PulmoTrack, the intensive care unit staff was similar in their ability to detect
      the absence of wheeze. The PulmoTrack was better than the staff in detecting
      wheeze.

PMID- 18811992
TI  - Readability assessment of internet-based consumer health information.
AB  - BACKGROUND: A substantial amount of consumer health-related information is
      available on the Internet. Studies suggest that consumer comprehension may be
      compromised if content exceeds a 7th-grade reading level, which is the average
      American reading level identified by the United States Department of Health and
      Human Services (USDHHS). OBJECTIVE: To determine the readability of Internet
      based consumer health information offered by organizations that represent the top
      5 medical-related causes of death in America. We hypothesized that the average
      readability (reading grade level) of Internet-based consumer health information
      on heart disease, cancer, stroke, chronic obstructive pulmonary disease, and
      diabetes would exceed the USDHHS recommended reading level. METHODS: From the Web
      sites of the American Heart Association, American Cancer Society, American Lung
      Association, American Diabetes Association, and American Stroke Association we
      randomly gathered 100 consumer-health-information articles. We assessed each
      article with 3 readability-assessment tools: SMOG (Simple Measure of
      Gobbledygook), Gunning FOG (Frequency of Gobbledygook), and Flesch-Kincaid Grade
      Level. We also categorized the articles per the USDHHS readability categories:
      easy to read (below 6th-grade level), average difficulty (7th to 9th grade
      level), and difficult (above 9th-grade level). RESULTS: Most of the articles
      exceeded the 7th-grade reading level and were in the USDHHS "difficult" category.
      The mean +/- SD readability score ranges were: SMOG 11.80 +/- 2.44 to 14.40 +/-
      1.47, Flesch-Kincaid 9.85 +/- 2.25 to 11.55 +/- 0.76, and Gunning FOG 13.10 +/-
      3.42 to 16.05 +/- 2.31. The articles from the American Lung Association had the
      lowest reading-level scores with each of the readability-assessment tools.
      CONCLUSIONS: Our findings support that Web-based medical information intended for
      consumer use is written above USDHHS recommended reading levels. Compliance with
      these recommendations may increase the likelihood of consumer comprehension.

PMID- 18811993
TI  - Sleep and respiratory function after withdrawal of noninvasive ventilation in
      patients with chronic respiratory failure.
AB  - BACKGROUND: In patients with restrictive thoracic disease, little is known about
      changes in sleep and breathing if the patient stops using nocturnal noninvasive
      ventilation (NIV). Better understanding of those changes may affect NIV
      management and improve our understanding of the relationship of night-to-night
      variability of respiratory and sleep variables and morning gas exchange. METHODS:
      With 6 stable patients with restrictive chronic respiratory failure who were
      being treated with home NIV we conducted a 5-step study: (1) The subject
      underwent an in-hospital baseline sleep study while on NIV, then next-morning
      pulmonary function tests. (2) At home, on consecutive nights, the subject
      underwent the same sleep-study measurements while not using NIV, until the
      patient had what we defined as respiratory decompensation (oxygen saturation
      measured via pulse oximetry [S(pO(2))] < 88% or end-tidal CO(2) pressure
      [P(ETCO(2))] > 50 mm Hg, with or without headaches, fatigue, or worsening
      dyspnea). Each morning after each home sleep-study night off NIV, we also
      measured S(pO(2)) and P(ETCO(2)). (3) The patient returned to the hospital for a
      second overnight assessment, the same as the baseline assessment except without
      NIV. (4) The patient went home and restarted using NIV with his or her pre-study
      NIV settings. (5) After the number of nights back on home NIV matched the number
      of nights the patient had been off NIV, the patient returned to the hospital for
      a third in-hospital assessment. We measured static lung volumes, maximum
      inspiratory and expiratory static mouth pressure, breathing pattern, arterial
      blood gases, S(pO(2)), P(ETCO(2)), and full overnight polysomnography values.
      RESULTS: Respiratory decompensation occurred 4-15 days after NIV discontinuation
      (mean 6.8 d). On the first and second in-hospital assessment nights,
      respectively, the mean nadir nocturnal S(pO(2)) values were 84 +/- 2% and 64 +/-
      4%, the total apnea-hypopnea index values were 0 +/- 0 and 9 +/- 2, and the
      obstructive hypopnea index values were 0 +/- 0 and 7 +/- 1 episodes per total
      sleep hour. Respiratory events started on the first night off NIV. Spirometry,
      muscle strength, and sleep architecture did not change significantly. With
      resumption of NIV, baseline conditions were recovered. CONCLUSIONS: NIV
      discontinuation in patients with restrictive chronic respiratory failure
      previously stabilized on NIV promptly leads to nocturnal respiratory failure and
      within days to diurnal respiratory failure. Stopping NIV for more than a day or
      two is not recommended.

PMID- 18811994
TI  - The institutional review board and you.

PMID- 18811995
TI  - The historical, ethical, and legal background of human-subjects research.
AB  - The current system of human-subject-research oversight and protections has
      developed over the last 5 decades. The principles of conducting human research
      were first developed as the Nuremberg code to try Nazi war criminals. The 3 basic
      elements of the Nuremberg Code (voluntary informed consent, favorable
      risk/benefit analysis, and right to withdraw without repercussions) became the
      foundation for subsequent ethical codes and research regulations. In 1964 the
      World Medical Association released the Declaration of Helsinki, which built on
      the principles of the Nuremberg Code. Numerous research improprieties between
      1950 and 1974 in the United States prompted Congressional deliberations about
      human-subject-research oversight. Congress's first legislation to protect the
      rights and welfare of human subjects was the National Research Act of 1974, which
      created the National Commission for Protection of Human Subjects of Biomedical
      and Behavioral Research, which issued the Belmont Report. The Belmont Report
      stated 3 fundamental principles for conducting human-subjects research: respect
      for persons, beneficence, and justice. The Office of Human Research Protections
      oversees Title 45, Part 46 of the Code for Federal Regulations, which pertains to
      human-subjects research. That office indirectly oversees human-subjects research
      through local institutional review boards (IRB). Since their inception, the
      principles of conducting human research, IRBs, and the Code for Federal
      Regulations have all advanced substantially. This paper describes the history and
      current status of human-subjects-research regulations.

PMID- 18811996
TI  - The purpose, composition, and function of an institutional review board:
      balancing priorities.
AB  - The institutional review board (IRB) is one part of the research enterprise
      designated to protect human subjects. At times the IRB can feel like an
      oppressive oversight body bound by regulations and designed to inhibit research.
      However, in reality the IRB was an attempt by the federal government to
      streamline a variety of processes to ensure the protection of human subjects.
      Growing out of a history of unethical scientific research, the principle goal of
      the IRB is to protect human subjects. At some institutions the IRB has an
      additional role, to take a second look at proposed scientific methods to ensure
      the highest quality research. The legal basis, purpose, composition, and function
      of an IRB, and potential challenges in human-subjects research are reviewed here.

PMID- 18811997
TI  - Informed consent: what is it? Who can give it? How do we improve it?
AB  - The freedom to choose is integral to our daily lives, directs our interactions
      with patients, and is a key component of our conduct of human-subjects research.
      Most of the historical errors and atrocities in human experimentation had at
      their core a failure of consent. In response to those events, national and
      international law developed to direct researchers to a process of informed
      consent to participate in research. The application of this process, though, can
      be challenging. What does this process look like? Does it require written
      documentation, and if so what type? Who can give informed consent? Though
      researchers worldwide would agree on the concept of informed consent, the nuts
      and bolts of applying this ideal can create obstacles to researchers, confusion
      to subjects, and increasing regulations that may or may not help achieve the
      goal. I will review the current regulatory guidelines, summarize the types of
      consent, and consider options for improving the informed-consent process.

PMID- 18811998
TI  - Protecting vulnerable subjects in clinical research: children, pregnant women,
      prisoners, and employees.
AB  - The federal government has established guidelines and regulations for the
      protection of vulnerable research subjects, especially children, pregnant women,
      cognitively impaired persons, and prisoners. In addition, students, residents,
      and employees are recognized as special research populations. Clinical
      investigators need to be aware of and use these federal guidelines appropriately.
      This article provides practical guidance for respiratory therapists who conduct
      research with these patient populations and solutions to the barriers
      investigators commonly encounter when studying these patient populations.

PMID- 18811999
TI  - Institutional review board consideration of chart reviews, case reports, and
      observational studies.
AB  - Though the need for human-subjects review is readily apparent to investigators
      when conducting a randomized clinical trial, that same requirement is often less
      obvious when considering activities such as chart reviews, observational studies,
      or even case reports. In some cases all that is needed is notification of the
      institutional review board, which might then exempt the research. In other cases,
      waiver of consent and Health Insurance Portability and Accountability Act
      authorization may be granted, whereas in some situations risk to privacy may be
      considered too great and approval denied. In all cases, including case reviews,
      quality-improvement projects, and chart reviews, the most cautious approach for
      the investigator is to discuss regulatory requirements with the institutional
      review board official to ensure compliance. I will review what constitutes human
      subjects research and how investigators may access protected health information,
      and consider some examples of observational research.

PMID- 18812000
TI  - Practical tips for working effectively with your institutional review board.
AB  - The federal government regulates human research with a local institutional review
      board (IRB) at your institution. Your IRB's main responsibility is to protect the
      rights and welfare of human subjects recruited to participate in research. The
      IRB is responsible for reviewing and approving all research protocols that
      involve human subjects. The IRB evaluates your study design to ensure that it has
      the possibility of answering your research hypothesis. The IRB focuses on the
      risks and benefits of your research. The IRB wants to know that research subjects
      are recruited fairly and that the potential for benefit is distributed equitably.
      They also want to know how you plan to protect research subjects from the risks
      of research and how you will manage the data, especially protected health
      information. Though the Code of Federal Regulations is extensive, this article
      provides information to help you navigate your research protocol through the
      layers of regulations, including the Privacy Rule of the Health Insurance
      Portability and Accountability Act of 1996. Whether conducting a simple chart
      review or participating in a multi-site randomized placebo-controlled trial, if
      you follow tried-and-true scientific methods and good clinical practice, you will
      be able to work effectively with your IRB.

PMID- 18812001
TI  - How to do human-subjects research if you do not have an institutional review
      board.
AB  - Biomedical research with human subjects has expanded outside of traditional
      medical centers and hospitals into other health care entities, such as
      rehabilitation facilities, free-standing out-patient treatment centers, and even
      home-health agencies. Regardless of the location, federal regulations mandate
      that all human-subjects research must be overseen by an institutional review
      board (IRB) or ethics committee to ensure the research abide by the Code of
      Federal Regulations. Consequently, all human-subjects research must be reviewed
      and approved by an IRB prior to initiation of any research procedures.
      Unfortunately, many of these nontraditional research facilities do not have easy
      access to an IRB. This does not render such research exempt from federal
      oversight. Clinicians at these facilities have viable options for obtaining IRB
      approval and legally conducting such research. This paper outlines the available
      options and their pros and cons.

PMID- 18812002
TI  - Bilateral diaphragm paralysis: a challenging diagnosis.

PMID- 18812003
TI  - Performance of transport ventilators.

PMID- 18812005
TI  - Chromatin dynamics in Triturus cristatus oogenesis: an epigenetic approach.
AB  - Oogenesis is a critical event in the formation of female gametes, whose role in
      development is to transfer genomic information to the next generation. During
      this process, the gene expression pattern changes dramatically concomitant with
      genome remodelling, while genomic information is stably maintained. The aim of
      the present study was to investigate the chromatin architecture in newt oocytes.
      Using fluorescence microscopy, as well as transmission electron microscopy (TEM),
      immunohistochemical method and RE-ChIP assay, some peculiar aspects of chromatin
      and chromosome organization and evolution in crested newt oogenesis were
      investigated. We focussed our investigations on detection of certain epigenetic
      modifications (H4 hyperacetylation, H2A ubiquitinylation and cytosine
      methylation) at the rRNA gene (18S-5.8S-28S) promoter region. Our findings
      suggest that there is an involvement of some epigenetic modifications as well as
      of linker histone variants in chromatin architecture dynamics during crested newt
      oogenesis.

PMID- 18812006
TI  - Barriers to the uptake of computerized cognitive behavioural therapy: a
      systematic review of the quantitative and qualitative evidence.
AB  - BACKGROUND: Studies of cognitive behavioural therapy delivered by computer (cCBT)
      show clinical efficacy for treating anxiety and depression, but have not focused
      on barriers to uptake. Potential barriers include adverse consequences,
      accessibility and acceptability. METHOD: An integrated systematic review was
      conducted of quantitative and qualitative studies and surveys from multiple
      electronic databases where computers delivered cCBT for anxiety or depression.
      RESULTS: Substantial numbers of potential participants are lost prior to trials
      commencing with little explanation. Among trial participants, drop-outs may be
      higher in the cCBT groups (odds ratio 2.03, 95% confidence interval 0.81-5.09).
      Only a median of 56% completed a full course of cCBT and personal circumstance
      was a more common cause of drop-out than difficulties with the technology or
      social background. Risk was rarely assessed in the majority of programs.
      Significant staff time was needed to support clients. Therapists were more
      negative about cCBT than clients. CONCLUSIONS: While cCBT is likely to be an
      effective and acceptable intervention for some people, there are barriers to its
      uptake that will substantially limit its impact if not addressed. These included
      investigating the outcome and attitudes of those who do not make it as far as
      cCBT trials and why so few finish a full course of cCBT.

PMID- 18812007
TI  - Altered prefrontal lobe oxygenation in bipolar disorder: a study by near-infrared
      spectroscopy.
AB  - BACKGROUND: Previous studies have reported prefrontal cortex (PFC)
      pathophysiology in bipolar disorder. METHOD: We examined the hemodynamics of the
      PFC during resting and cognitive tasks in 29 patients with bipolar disorder and
      27 healthy controls, matched for age, verbal abilities and education. The
      cognitive test battery consisted of letter and category fluency (LF and CF), Sets
      A and B of the Raven's Colored Progressive Matrices (RCPM-A and RCPM-B) and the
      letter cancellation test (LCT). The tissue oxygenation index (TOI), the ratio of
      oxygenated hemoglobin (HbO2) concentration to total hemoglobin concentration, was
      measured in the bilateral PFC by spatially resolved near-infrared spectroscopy.
      Changes in HbO2 concentration were also measured. RESULTS: The bipolar group
      showed slight but significant impairment in performance for the non-verbal tasks
      (RCPM-A, RCPM-B and LCT), with no significant between-group differences for the
      two verbal tasks (LF and CF). A group x task x hemisphere analysis of variance
      (ANOVA) on the TOI revealed an abnormal pattern of prefrontal oxygenation across
      different types of cognitive processing in the bipolar group. Post hoc analyses
      following a group x task x hemisphere ANOVA on HbO2 concentration revealed that
      the bipolar group showed a greater increase in HbO2 concentration in the LCT and
      in RCPM-B, relative to controls. CONCLUSIONS: Both indices of cortical activation
      (TOI and HbO2 concentration) indicated a discrepancy in the PFC function between
      verbal versus non-verbal processing, indicating task-specific abnormalities in
      the hemodynamic control of the PFC in bipolar disorder.

PMID- 18812008
TI  - Magnitude and contributory factors of postnatal depression: a community-based
      cohort study from a rural subdistrict of Bangladesh.
AB  - BACKGROUND: Recent evidence suggests that the prevalence of postnatal depression
      (PND) is highest in low-income developing countries. This study aimed to estimate
      the prevalence of PND and its associated risk factors among Bangladeshi women.
      METHOD: The study was conducted in the Matlab subdistrict of rural Bangladesh. A
      cohort of 346 women was followed up from late pregnancy to post-partum.
      Sociodemographic and other related information on risk factors was collected on
      structured questionnaires by trained interviewers at 34-35 weeks of pregnancy at
      the woman's home. A validated local language (Bangla) version of the Edinburgh
      Postnatal Depression Scale (EPDS-B) was used to measure depression status at 34
      35 weeks of pregnancy and at 6-8 weeks after delivery. RESULTS: The prevalence of
      PND was 22% [95% confidence interval (CI) 17.7-26.7%] at 6-8 weeks post-partum.
      After adjustment in a multivariate logistic model, PND could be predicted by
      history of past mental illness [odds ratio (OR) 5.6, 95% CI 1.1-27.3], depression
      in current pregnancy (OR 6.0, 95% CI 3.0-12.0), perinatal death (OR 14.1, 95% CI
      2.5-78.0), poor relationship with mother-in-law (OR 3.6, 95% CI 1.1-11.8) and
      either the husband or the wife leaving home after a domestic quarrel (OR 4.0, 95%
      CI 1.6-10.2). CONCLUSIONS: The high prevalence of PND in the study was similar to
      other countries in the South Asian region. The study findings highlight the need
      for programme managers and policy makers to allocate resources and develop
      strategies to address PND in Bangladesh.

PMID- 18812010
TI  - Induction of immunity in sheep to Fasciola hepatica with mimotopes of cathepsin L
      selected from a phage display library.
AB  - An M13 phage random 12-mers peptide library was used to screen cathepsin L
      mimotopes of Fasciola hepatica and to evaluate their immunogenicity in sheep.
      Seven clones showed positive reactivity to a rabbit anti-cathepsin L1/L2
      antiserum in ELISA, and their amino acid sequences deduced by DNA sequencing were
      tentatively mapped on the protein. Twenty sheep were randomly allocated into 4
      groups of 5 animals each, for immunization with 1x10(14) phage particles of
      clones 1, 20, a mixture of 7 clones and PBS, without adjuvant at the beginning,
      and 4 weeks later. All groups were challenged with 300 metacercariae at week 6
      and slaughtered 16 weeks later. The mean worm burdens after challenge were
      reduced by 47.61% and 33.91% in sheep vaccinated with clones 1 and 20,
      respectively; no effect was observed in animals inoculated with the clone
      mixture. Also, a significant reduction in worm size and burden was observed for
      those sheep immunized with clone 1. Animals receiving clone 20, showed a
      significant reduction in egg output. Immunization induced a reduction of egg
      viability ranging from 58.92 to 82.11%. Furthermore, vaccinated animals produced
      clone-specific antibodies which were boosted after challenge with metacercariae
      of F. hepatica.

PMID- 18812009
TI  - Brainstem volumetric alterations in children with autism.
AB  - BACKGROUND: Although several studies have examined brainstem volume in autism,
      results have been mixed and no investigation has specifically measured gray- and
      white-matter structures. The aim of this investigation was to assess gray- and
      white-matter volumes in children with autism. METHOD: Subjects included 22 right
      handed, non-mentally retarded boys with autism and 22 gender- and age-matched
      controls. Magnetic resonance imaging (MRI) scans were obtained using a 1.5-T
      scanner and volumetric measurements were performed using the BRAINS2 software
      package. Gray- and white-matter volumes were measured using a semi-automated
      segmentation process. RESULTS: There were no significant differences in age and
      total brain volume (TBV) between the two groups but full-scale IQ was higher in
      controls. A decrease in brainstem gray-matter volume was observed in the autism
      group before and after controlling for TBV. No significant differences were
      observed in white-matter volume. A significant relationship was observed between
      brainstem gray-matter volume and oral sensory sensitivity as measured by the
      Sensory Profile Questionnaire (SPQ). CONCLUSIONS: Findings from this study are
      suggestive of brainstem abnormalities in autism involving gray-matter structures
      with evidence supporting the existence of a relationship between these
      alterations and sensory deficits. These results are consistent with previous
      investigations and support the existence of disturbances in brainstem circuitry
      thought to be implicated in the sensory dysfunction observed in autism.

PMID- 18812011
TI  - Inter- and intra-specific exposure to parasites and pathogens via the faecal-oral
      route: a consequence of behaviour in a patchy environment.
AB  - Livestock herbivores are at risk of inter- and intra-specific exposure to
      parasites/pathogens via the faecal-oral route during grazing. Each contact
      between livestock and faeces in the environment is a potential parasite/pathogen
      transmission event. Cattle grazing contact with faeces varies in relation to the
      species depositing the faeces and the distribution of the faeces. We used a
      foraging model to simulate the grazing behaviour of beef cattle in two grazing
      systems to compare the relative inter-specific and intra-specific exposure risks
      to parasites/pathogens. Overall, there is a greater level of intra- vs. inter
      specific risk via the faecal-oral route. However, under certain conditions,
      particularly for microparasite infections, e.g. paratuberculosis in rabbits and
      bovine tuberculosis in badgers, wildlife may pose a significant exposure risk to
      parasites/pathogens. These risks can be enhanced when cattle are first turned out
      onto pasture and in situations where intra-specific variations in wildlife
      behaviour result in more dispersed defecation patterns.

PMID- 18812012
TI  - The current strategy of repair of tetralogy of Fallot in children and adults.
AB  - OBJECTIVES: The strategies of repair of tetralogy of Fallot change with the age
      of patients. In children older than 4 years and adults, the optimal strategy may
      be to use different method of reconstruction of the right ventricular outflow
      tract from those followed in younger children, so as to avoid, or reduce, the
      pulmonary insufficiency that is increasingly known to compromise right
      ventricular function. METHODS: From April, 2001, through May, 2008, we undertook
      complete repair in 312 patients, 180 male and 132 female, with a mean age of 11.3
      years +/-0.4 years, and a range from 4 to 48 years, with typical clinical and
      morphological features of tetralogy of Fallot, including 42 patients with the
      ventriculo-arterial connection of double outlet right ventricle. The operation
      was performed under moderate hypothermia using blood cardioplegia. The
      ventricular septal defect was closed with a Dacron patch. When it was considered
      necessary to resect the musculature within the right ventricular outflow tract,
      or perform pulmonary valvotomy, we sought to preserve the function of the
      pulmonary valve by protecting as far as possible the native leaflets, or creating
      a folded monocusp of autologous pericardium. RESULTS: The repair was achieved
      completely through right atrium in 192, through the right ventricular outflow
      tract in 83, and through the right atrium, the outflow tract, and the pulmonary
      trunk in 36 patients. A transjunctional patch was inserted in 169 patients, non
      valved in all but 9. There were no differences regarding the periods of aortic
      cross-clamping or cardiopulmonary bypass. Of the patients, 5 died (1.6%), with no
      influence noted for the transjunctional patch. Of those having a non-valved patch
      inserted, three-tenths had pulmonary regurgitation of various degree, while those
      having a valved patch had minimal pulmonary insufficiency and good right
      ventricular function postoperatively, this being maintained after follow-up of 8
      to 24-months. CONCLUSIONS: Based on our experience, we suggest that the current
      strategy of repair of tetralogy of Fallot in older children and adults should be
      based on minimizing the insertion of transjunctional patches, this being
      indicated only in those with very small ventriculo-pulmonary junctions. If such a
      patch is necessary, then steps should be taken to preserve the function of the
      pulmonary valve.

PMID- 18812013
TI  - S100B overexpressing mutant mice exhibit prolonged behavioural and biochemical
      responses towards repeated intermittent binge treatments with MDMA.
AB  - The recreational drug 3,4-methylenedioxy-metamphetamine (MDMA; 'ecstasy')
      enhances serotonin and dopamine transmission. Repeated binge treatment with MDMA
      (5 mg/kg, 3 times daily, 3 h apart, once per week for 4 wk) was found to increase
      gene expression of S100B, a neurotrophic factor that modulates neuronal
      plasticity. Mutant mice overexpressing S100B were investigated to better
      understand how increased S100B expression may influence MDMA-induced biochemical
      and behavioural responses. In open-field behaviour, the later MDMA binges
      decreased rearing and thigmotaxis in S100B mutant mice compared to wild-type
      mice. In the elevated plus-maze, MDMA increased open-arm entries in both
      genotypes, but less tolerance to this effect was found in S100B mutant mice.
      Serotonin transporter (SERT) density was up-regulated in the substantia nigra in
      S100B mutant mice under baseline conditions. MDMA treatment increased SERT in
      wild-type mice, but did not further increase it in S100B mutant mice. Dopamine
      transporter density was down-regulated by MDMA in both genotypes in the striatum.
      5-HT1B receptor density and G-protein coupling were higher in MDMA-treated S100B
      mutant mice than in saline-treated mutant mice and MDMA-treated wild-type mice in
      the medial globus pallidus. In conclusion, repeated MDMA treatment increases
      S100B mRNA. Certain explorative and anxiolytic-like behaviours in response to
      MDMA are potentiated and exhibit less tolerance in mice overexpressing S100B. The
      genotype-dependent behavioural responses are paralleled by adaptations in the
      serotonin system. Our data indicate that genetic differences in S100B gene
      expression may predispose individual differences in the responsivity to repeated
      intake of MDMA.

PMID- 18812014
TI  - Bacterial flagellar motor.
AB  - The bacterial flagellar motor is a reversible rotary nano-machine, about 45 nm in
      diameter, embedded in the bacterial cell envelope. It is powered by the flux of
      H+ or Na+ ions across the cytoplasmic membrane driven by an electrochemical
      gradient, the proton-motive force or the sodium-motive force. Each motor rotates
      a helical filament at several hundreds of revolutions per second (hertz). In many
      species, the motor switches direction stochastically, with the switching rates
      controlled by a network of sensory and signalling proteins. The bacterial
      flagellar motor was confirmed as a rotary motor in the early 1970s, the first
      direct observation of the function of a single molecular motor. However, because
      of the large size and complexity of the motor, much remains to be discovered, in
      particular, the structural details of the torque-generating mechanism. This
      review outlines what has been learned about the structure and function of the
      motor using a combination of genetics, single-molecule and biophysical
      techniques, with a focus on recent results and single-molecule techniques.

PMID- 18812015
TI  - Protein-protein interaction and quaternary structure.
AB  - Protein-protein recognition plays an essential role in structure and function.
      Specific non-covalent interactions stabilize the structure of macromolecular
      assemblies, exemplified in this review by oligomeric proteins and the capsids of
      icosahedral viruses. They also allow proteins to form complexes that have a very
      wide range of stability and lifetimes and are involved in all cellular processes.
      We present some of the structure-based computational methods that have been
      developed to characterize the quaternary structure of oligomeric proteins and
      other molecular assemblies and analyze the properties of the interfaces between
      the subunits. We compare the size, the chemical and amino acid compositions and
      the atomic packing of the subunit interfaces of protein-protein complexes,
      oligomeric proteins, viral capsids and protein-nucleic acid complexes. These
      biologically significant interfaces are generally close-packed, whereas the non
      specific interfaces between molecules in protein crystals are loosely packed, an
      observation that gives a structural basis to specific recognition. A distinction
      is made within each interface between a core that contains buried atoms and a
      solvent accessible rim. The core and the rim differ in their amino acid
      composition and their conservation in evolution, and the distinction helps
      correlating the structural data with the results of site-directed mutagenesis and
      in vitro studies of self-assembly.

PMID- 18812016
TI  - Effect of non-persistent use of oral glucose-lowering drugs on HbA1c goal
      attainment.
AB  - OBJECTIVES: The aim of this study was to quantify the effect of non-persistence
      with oral glucose-lowering drugs (OGLD) on HbA(1c) goal attainment (<7%) in daily
      practice. METHODS: From the PHARMO Record Linkage System comprising among others
      linked drug dispensing and clinical laboratory data from approximately 2.5
      million individuals in the Netherlands, new users of OGLD in the period 1999-2004
      were identified. Patients with a baseline HbA(1c) > or =7% and at least one
      HbA(1c) measurement in the period of 6-12 months after treatment onset were
      included in the study cohort. Persistence with OGLD in the first year of
      treatment was determined using the method of Catalan. In case the first treatment
      episode overlapped the first HbA(1c) measurement within 6-12 months after
      treatment onset, a patient was considered persistent at that measurement.
      Patients with a HbA(1c) <7% were defined as having attained goal. RESULTS: The
      study cohort included 2023 patients with a mean baseline HbA(1c) of 8.9 +/- 1.8%.
      Three-quarters (1512 patients) were persistent with any OGLD at the first HbA(1c)
      measurement within 6-12 months after treatment onset; of these, 861 (57%) were at
      goal. Of the 511 non-persistent patients, 239 (47%) were at goal. Non-persistent
      patients were about 20% less likely to attain goal (RRadj 0.82; 95%CI 0.74-0.91),
      compared to persistent OGLD users. CONCLUSION: Non-persistent use of OGLD leads
      to a 20% decreased probability of HbA(1c) goal attainment in daily practice. This
      effect of non-persistence seems modest, but represents around 12 000 new and 10
      000 prevalent OGLD users a year in the Netherlands in whom OGLD use could be
      better controlled.

PMID- 18812017
TI  - Assessment of adherence, persistence, and costs among valsartan and
      hydrochlorothiazide retrospective cohorts in free-and fixed-dose combinations.
AB  - OBJECTIVES: To assess medication adherence, persistence, and costs between
      cohorts of patients in managed care settings using a fixed-dose combination (FDC)
      or individual components (IC) of valsartan and hydrochlorothiazide in an
      insurance claims database. METHODS: Medical and prescription claims for
      hypertensive patients using a combination of valsartan and HCTZ were identified
      from the IHCIS National Managed Care Benchmark Database via a retrospective
      cohort analysis. Study subjects had at least 110 days prior to start of study
      medications during which no other antihypertensive medications were prescribed,
      and were followed for 12 months. Claims for 8711 adult patients were analyzed for
      adherence, persistence and costs. General linear regression was conducted to
      detect differences in adherence among groups. Covariates included age, gender,
      persistence, number on concomitant cardiovascular drugs, and number of
      cardiovascular diagnoses. RESULTS: Most subjects used an FDC product (N=8150,
      93.6%) vs. the IC (N=561, 6.4%). The FDC group had a larger portion of males and
      less concomitant cardiovascular medications or disease. A random sample of 1628
      of the FDC subjects had improved values for medication adherence compared to the
      IC group (62.1 vs. 53.0%, p<0.001) and persistence values were improved at both
      180 days (73 vs. 28%, p<0.001) and 365 days (54 vs. 19%, p<0.001). Both
      prescription drug costs ($1587 vs. $2050, p<0.001) and medical costs ($3343 vs.
      $3817, p<0.001) were lower in the FDC cohorts. CONCLUSIONS: The use of fixed-dose
      therapy in hypertension may lead to increased adherence and persistence with a
      positive financial impact on both prescription and total medical costs. As with
      any retrospective claims database analysis, unobserved systematic differences
      between the two medication groups may exist.

PMID- 18812018
TI  - Formed and preformed metabolites: facts and comparisons.
AB  - The administration of metabolites arising from new drug entities is often
      employed in drug discovery to investigate their associated toxicity. It is
      expected that administration of metabolites can predict the exposure of
      metabolites originating from the administration of precursor drug. Whether exact
      and meaningful information can be obtained from this has been a topic of debate.
      This communication summarizes observations and theoretical relationships based on
      physiological modelling for the liver, kidney and intestine, three major
      eliminating organs/tissues. Theoretical solutions based on physiological
      modelling of organs were solved, and the results suggest that deviations are
      expected. Here, examples of metabolite kinetics observed mostly in perfused
      organs that did not match predictions are provided. For the liver, discrepancies
      in fate between formed and preformed metabolites may be explained by the
      heterogeneity of enzymes, the presence of membrane barriers and whether
      transporters are involved. For the kidney, differences have been attributed to
      glomerular filtration of the preformed but not the formed metabolite. For the
      intestine, the complexity of segregated flows to the enterocyte and serosal
      layers and differences in metabolism due to the route of administration are
      addressed. Administration of the metabolite may or may not directly reflect the
      toxicity associated with drug use. However, kinetic data on the preformed
      metabolite will be extremely useful to develop a sound model for modelling and
      simulations; in-vitro evidence on metabolite handling at the target organ is also
      paramount. Subsequent modelling and simulation of metabolite data arising from a
      combined model based on both drug and preformed metabolite data are needed to
      improve predictions on the behaviours of formed metabolites.

PMID- 18812019
TI  - Artemisinin derivatives with long elimination half-life.

PMID- 18812020
TI  - Formulation and evaluation of primaquine phosphate taste-masked rapidly
      disintegrating tablet.
AB  - This work investigates the complete bitter-taste-masking of primaquine phosphate
      (PRM) using a solid dispersion with mono ammonium glycyrrhyzinate pentahydrate
      (GLY). This work also describes the preparation of rapidly disintegrating tablets
      (RDTs) of PRM by a direct compression method using superdisintegrant,
      croscarmellose sodium. A solid dispersion was prepared by the solvent evaporation
      method. Fourier transform infrared spectroscopy (FTIR) and differential scanning
      calorimetry (DSC) were performed to identify the physicochemical interaction
      between drug and carrier, hence its effect on dissolution. In-vitro drug release
      studies were performed for RDTs at both pH 1.2 and 6.8. Bitterness score was
      evaluated using a human gustatory sensation test. FTIR spectroscopy and DSC
      showed no interaction of PRM in GLY solid dispersion. RDTs prepared from solid
      dispersion showed complete bitter-taste-masking of PRM. RDTs containing solid
      dispersion exhibited a better dissolution profile, at both pH 1.2 and 6.8, than
      pure PRM. Thus, the solid dispersion technique can be successfully used for
      complete bitter taste masking of PRM.

PMID- 18812021
TI  - Delivery of daunorubicin to cancer cells with decreased toxicity by association
      with a lipidic nanoemulsion that binds to LDL receptors.
AB  - A lipidic nanoemulsion termed LDE concentrates in neoplastic cells after
      injection into the bloodstream and thus can be used as a drug carrier to tumour
      sites. The chemotherapeutic agent daunorubicin associates poorly with LDE; the
      aim of this study was to clarify whether the derivatization of daunorubicin by
      the attachment of an oleyl group increases the association with LDE, and to test
      the cytotoxicity and animal toxicity of the new preparation. The association of
      oleyl-daunorubicin (oDNR) to LDE showed high yield (93 +/- 2% and 84 +/- 4% at
      1:10 and 1:5 drug:lipid mass, respectively) and was stable for at least 20 days.
      Association with oDNR increased the LDE particle diameter from 42 +/- 4 nm to 75
      +/- 6 nm. Cytotoxicity of LDE-oDNR was reduced two-fold in HL-60 and K-562 cell
      lines, fourteen-fold in B16 cells and nine-fold in L1210 cells when compared with
      commercial daunorubicin. When tested in mice, LDE-oDNR showed remarkable reduced
      toxicity (maximum tolerated dose > 253 micromol kg(-1), compared with <3 micromol
      kg(-1) for commercial daunorubicin). At high doses, the cardiac tissue of LDE
      oDNR-treated animals had much smaller structural lesions than with commercial
      daunorubicin. LDE-oDNR is therefore a promising new preparation that may offer
      superior tolerability compared with commercial daunorubicin.

PMID- 18812022
TI  - Development and in-vitro evaluation of a colon-specific controlled release drug
      delivery system.
AB  - The major challenges in targeting drug to various parts of the gastrointestinal
      tract include control of drug release with respect to its environment and transit
      time. These two variables should be taken into consideration in designing a
      rational colonic drug delivery system. To this end, a swelling matrix core
      containing pectin, hydroxypropyl methylcellulose (HPMC), microcrystalline
      cellulose and 5-aminosalicylic acid was developed. This was subjected to a dual
      coating operation: an inner pH-sensitive enteric and an outer semi-permeable
      membrane coat with a pore former. In-vitro dissolution studies were carried out
      in USP apparatus-I using sequential pH media. The first 2 h of dissolution
      studies were done in HCl buffer at pH 1.5, the next 2 h in pH 5.5 and, finally,
      in phosphate buffer at pH 6.8 with and without pectinolytic enzyme present. Less
      than 2% drug was released in the first 6 h and about 90% released in the
      following 12 h in a controlled manner. The stability studies of the coated
      systems were performed for 90 days under various conditions and it was found that
      drug release was not adversely affected. Results indicate that this delivery
      system has potential for site-specific delivery of drugs to the colon
      irrespective of transit time and rapid changes in the proximal pH of the
      gastrointestinal tract.

PMID- 18812023
TI  - Lack of difference in pulmonary absorption of digoxin, a P-glycoprotein
      substrate, in mdr1a-deficient and mdr1a-competent mice.
AB  - Although in-vitro experiments have suggested that P-glycoprotein (P-gp) may have
      an important influence on the disposition of inhaled drugs, the effect of P-gp on
      absorption from the lung in-vivo has not been reported previously. The aim of
      this study was to compare the pulmonary absorption of digoxin, a well
      characterised substrate for P-gp, in mdr1a (-/-) (P-gp-deficient) and mdr1a (+/+)
      (P-gp-competent) mice. Digoxin was administered by intratracheal instillation
      over 3-4 s, a method demonstrated to result in dispersion of the dose to all
      regions of the lung. Drug distribution was determined in the lungs, plasma,
      brain, heart, liver and kidney of individual mice after 5, 10, 30, 60 and 90 min.
      Digoxin was cleared rapidly from the lung after intratracheal administration. No
      differences were observed in the maximum serum concentrations between mdr1a (+/+)
      and mdr1a (-/-) mice (37.8 +/- 6.9 and 38.8 +/- 15.8 ng mL(-1), respectively).
      The serum concentration versus time profiles were similar in both strains; the
      area under the drug serum concentration versus time curve (AUC) was 2010 and 1812
      ng mL(-1) min in mdr1a (-/-) and mdr1a (+/+) mice, respectively. For organs
      harvested at the end of the experiment (90 min), the only significant difference
      between the strains was the markedly elevated concentration of digoxin in the
      brains of mdr1a (-/-) mice. In conclusion, digoxin is rapidly absorbed from the
      mouse lung following tracheal instillation, with no difference in the rate or
      extent of absorption between mdr1a-deficient and -competent mice. This suggests
      that, in contrast to the scenario suggested by in-vitro data, P-gp in the
      respiratory epithelium may have little influence on the disposition of drugs that
      are well absorbed from the lung.

PMID- 18812024
TI  - An evaluation of the relative roles of the unstirred water layer and receptor
      sink in limiting the in-vitro intestinal permeability of drug compounds of
      varying lipophilicity.
AB  - The roles of the unstirred water layer (UWL) and receptor sink on the in-vitro
      transmembrane permeability of an increasingly lipophilic series of compounds
      (mannitol (MAN), diazepam (DIA) and cinnarizine (CIN)) have been assessed.
      Altered carbogen bubbling rates were used as a means to change the UWL thickness
      and polysorbate-80 (PS-80), bovine serum albumin (BSA) and alpha-1-acid
      glycoprotein (AAG) were employed to alter sink conditions. After correction for
      solubilisation, Papp data for MAN, DIA and CIN were consistent across varying
      donor PS-80 concentrations suggesting that for the drugs examined here, the donor
      UWL did not limit in-vitro permeability. Similarly, altered bubbling rates and
      receptor sink conditions had no impact on the permeability of MAN. In contrast,
      decreasing the size of the receptor UWL or adding solubilising agents to the
      receptor sink resulted in modest enhancements to the permeability of the more
      lipophilic probe DIA. For the most lipophilic compound, CIN, very significant
      changes to measured permeability (>30 fold) were possible, but were most evident
      only after concomitant changes to both the UWL and sink conditions, suggesting
      that the effectiveness of enhanced sink conditions were dependent on a decrease
      in the width of the UWL.

PMID- 18812025
TI  - Pharmacokinetic differentiation of drug candidates using system analysis and
      physiological-based modelling. Comparison of C.E.R.A. and erythropoietin.
AB  - Evaluation of the pharmacokinetics (PKs) in a proper physiological context is
      paramount to elucidate the factors that may improve a drug's PK properties. Using
      modern system analysis-based physiological modelling principles, this work
      applies a novel kinetic analysis framework to a PK comparison of two
      erythropoietically active drugs, C.E.R.A. (continuous erythropoietin receptor
      activator) and recombinant human erythropoietin (Epo), aimed at elucidating the
      main factors responsible for the substantial PK differences seen. The evaluation
      according to the new model is compared with a compartmental model analysis. Sheep
      (n = 7 for Epo; n = 8 for C.E.R.A.) received intravenous bolus injections of Epo
      and C.E.R.A. Baseline and 20-30 blood samples per injection were assayed by
      radioimmunoassay. Fundamental physiologically based PK building block principles
      were introduced, proceeding to the construction of a general PK model and several
      sub-models from which a final PK model was selected based on information
      theoretical principles. The compartmental comparison analysis use a two
      compartment model with central Michaelis-Menten elimination. Several lines of
      evidence support the hypothesis that the desirable slow elimination of C.E.R.A.
      relative to Epo is mainly caused by a smaller recirculation extraction fraction,
      which appears more influential on the elimination kinetics than the mean
      circulation transit time. The compartmental analysis demonstrates large
      differences in several PK parameters that contribute to C.E.R.A.'s slower
      elimination, consistent with the recirculation model analysis. It is hypothesized
      that C.E.R.A.'s smaller recirculatory extraction fraction is due to a reduced
      receptor-mediated elimination, consistent with in-vitro measurements where
      C.E.R.A. shows Epo-receptor binding with a lower association constant and a
      larger dissociation constant.

PMID- 18812026
TI  - Bis(alpha-furancarboxylato)oxovanadium(IV) prevents and improves dexamethasone
      induced insulin resistance in 3T3-L1 adipocytes.
AB  - Previous studies showed that bis(alpha-furancarboxylato)oxovanadium(IV) (BFOV),
      an orally active anti-diabetic organic vanadium complex, could improve insulin
      resistance in animals with type 2 diabetes. The present study has been carried
      out to evaluate the effects of BFOV on insulin-resistant glucose metabolism using
      dexamethasone-treated 3T3-L1 adipocytes as an in-vitro model of insulin
      resistance. The results showed that BFOV, similar to vanadyl sulfate and
      rosiglitazone, caused a concentration-dependent increase in glucose consumption
      by insulin-resistant adipocytes. Moreover, BFOV enhanced the action of insulin
      and completely prevented the development of insulin resistance induced by
      dexamethasone, leading to glucose consumption equal to that by normal cells. In
      addition, dexamethasone reduced the mRNA expression of insulin receptor substrate
      1 (IRS-1) and glucose transporter 4 (GLUT4) in 3T3-L1 adipocytes, while BFOV
      normalized the expression of IRS-1 and GLUT4. These findings suggest that BFOV
      prevents and improves dexamethasone-induced insulin resistance in 3T3-L1
      adipocytes by enhancing expression of IRS-1 and GLUT4 mRNA.

PMID- 18812027
TI  - Suppressive potencies of calcineurin inhibitors against the mitogen-induced
      blastogenesis of peripheral-blood mononuclear cells of myasthenia gravis
      patients.
AB  - The calcineurin inhibitors, tacrolimus and ciclosporin, are two useful
      immunosuppressive drugs for the treatment of myasthenia gravis (MG), for patients
      who have low responses to glucocorticoids. We have studied the suppressive
      potencies of tacrolimus and ciclosporin on concanavalin A-induced blastogenesis
      of peripheral-blood mononuclear cells (PBMCs) obtained from 38 MG patients and 26
      healthy volunteers. Differences in the IC50 values of the two calcineurin
      inhibitors between the patients and the healthy subjects were evaluated. The
      median (range) IC50 values for tacrolimus and ciclosporin on the blastogenesis of
      PBMCs of MG patients were 0.06 (0.001-100) and 0.41 (0.09-83.0) ng mL(-1),
      respectively. In contrast, the median (range) IC50 values of tacrolimus and
      ciclosporin on healthy PBMCs were 0.16 (0.001-0.33) and 5.59 (1.4-31.3),
      respectively, and thus ciclosporin potencies against PBMCs of MG patients were
      significantly higher than those against PBMCs of healthy subjects (P < 0.0001).
      The differences in tacrolimus IC50 values between the patients and healthy
      subjects were not significant. There was a correlation between ciclosporin IC50
      values against the blastogenesis of PBMCs of MG patients and the duration of the
      disease (r = 0.35, P = 0.049). A significant correlation between the IC50 values
      of ciclosporin and those of prednisolone against the blastogenesis of PBMCs of MG
      patients was also observed (r = 0.56, P = 0.003). Furthermore, the ciclosporin
      IC50 values significantly correlated with the periods of glucocorticoid
      administration for MG treatment (r = 0.42, P = 0.038). Such correlations were not
      observed with the tacrolimus IC50 values. These results suggested that
      glucocorticoid administration had an influence on PBMC response to the
      suppressive efficacy of ciclosporin in MG.

PMID- 18812028
TI  - The anti-arthritic effect of ursolic acid on zymosan-induced acute inflammation
      and adjuvant-induced chronic arthritis models.
AB  - Ursolic acid (UA) is pentacyclic triterpenoic acid that naturally occurs in many
      medicinal herbs and plants. In this study, we examined the possible suppressive
      effect of UA extracted from Oldenlandia diffusa on zymosan-induced acute
      inflammation in mice and complete Freund's adjuvant (CFA)-induced arthritis in
      rats. UA treatment (per oral) dose-dependently (25-200 mg kg(-1)) suppressed
      zymosan-induced leucocyte migration and prostaglandin E2 (PGE(2)) production in
      the air pouch exudates. Since the maximal effective dose of UA was 50 mg kg(-1)
      in the zymosan experiment, we used this dose of UA in a subsequent study using an
      adjuvant-induced rheumatoid arthritis model. UA treatment (50 mg kg(-1), per
      oral, once a day for 10 days) was started from day 12 after adjuvant injection.
      UA dramatically inhibited paw swelling, plasma PGE(2) production and radiological
      changes in the joint caused by CFA injection. Moreover, UA significantly
      suppressed the arthritis-induced mechanical and thermal hyperalgesia as well as
      the spinal Fos expression, as determined by immunohistochemistry, which was
      increased by CFA injection. In addition, overall anti-arthritic potency of UA was
      comparable with ibuprofen (100 mg kg(-1), oral) while UA did not induce
      significant gastric lesions as compared with the ibuprofen treatment group. These
      findings strongly suggest that UA is a useful suppressive compound for rheumatoid
      arthritis treatment with low risk of gastric problems.

PMID- 18812029
TI  - Microinjection of morphine into thalamic nucleus submedius depresses bee venom
      induced inflammatory pain in the rat.
AB  - Previous studies have provided evidence of the existence of a pain modulatory
      feedback pathway consisting of thalamic nucleus submedius (Sm)-ventrolateral
      orbital cortex-periaqueductal grey pathway, which is activated during acute pain
      and leads to depression of transmission of nociceptive information in the spinal
      dorsal horn. The aim of this study was to test the hypothesis that morphine
      microinjection into the Sm decreased spontaneous pain and bilateral thermal
      hyperalgesia, as well as ipsilateral mechanical allodynia, induced by
      subcutaneous injections of bee venom into the rat hind paw. Morphine (1.0, 2.5 or
      5.0 microg in 0.5 microL) injected into the Sm, contralateral to the bee venom
      injected paw, depressed spontaneous nociceptive behaviour in a dose-dependent
      manner. Furthermore, morphine significantly decreased bilateral thermal
      hyperalgesia and ipsilateral mechanical allodynia 2 h after bee venom injection.
      These morphine-induced effects were antagonized by 1.0 microg naloxone (an opioid
      antagonist) microinjected into the Sm 5 min before morphine administration. The
      results provided further support for the important role of the Sm and Sm-opioid
      receptors in inhibiting nociceptive behaviour and indicated for the first time
      that Sm opioid receptors were also effective in inhibiting the hypersensitivity
      provoked by bee venom-induced inflammation.

PMID- 18812030
TI  - Astaxanthin, a dietary carotenoid, protects retinal cells against oxidative
      stress in-vitro and in mice in-vivo.
AB  - We have investigated whether astaxanthin exerted neuroprotective effects in
      retinal ganglion cells in-vitro and in-vivo. In-vitro, retinal damage was induced
      by 24-h hydrogen peroxide (H2O2) exposure or serum deprivation, and cell
      viability was measured using a WST assay. In cultured retinal ganglion cells (RGC
      5, a rat ganglion cell-line transformed using E1A virus), astaxanthin inhibited
      the neurotoxicity induced by H2O2 or serum deprivation, and reduced the
      intracellular oxidation induced by various reactive oxygen species (ROS).
      Furthermore, astaxanthin decreased the radical generation induced by serum
      deprivation in RGC-5. In mice in-vivo, astaxanthin (100 mg kg(-1), p.o., four
      times) reduced the retinal damage (a decrease in retinal ganglion cells and in
      thickness of inner plexiform layer) induced by intravitreal N-methyl-D-aspartate
      (NMDA) injection. Furthermore, astaxanthin reduced the expressions of 4-hydroxy-2
      nonenal (4-HNE)-modified protein (indicator of lipid peroxidation) and 8-hydroxy
      deoxyguanosine (8-OHdG; indicator of oxidative DNA damage). These findings
      indicated that astaxanthin had neuroprotective effects against retinal damage in
      vitro and in-vivo, and that its protective effects may have been partly mediated
      via its antioxidant effects.

PMID- 18812031
TI  - Muscarinic, Ca(++) antagonist and specific butyrylcholinesterase inhibitory
      activity of dried ginger extract might explain its use in dementia.
AB  - Ginger rhizome (Zingiber officinale) has been used for centuries to treat
      dementia in South Asia. This study was undertaken to possibly justify its use. A
      70% aqueous/methanolic extract of dried ginger (Zo.Cr) was used. Zo.Cr tested
      positive for the presence of terpenoids, flavonoids, secondary amines, phenols,
      alkaloids and saponins. When tested on isolated rat stomach fundus, Zo.Cr showed
      a spasmogenic effect (0.03-5.00 mg mL(-1)); it relaxed the tissue at
      concentrations > or =5 mg mL(-1). The stimulant effect was resistant to blockade
      by hexamethonium and methysergide, but sensitive to atropine, indicating activity
      via muscarinic receptors. In atropinized (0.1 microM) preparations, Zo.Cr (0.3
      3.0 mg mL(-1)) relaxed high K(+) (80 mM)-induced contractions, indicating Ca(++)
      antagonism in addition to the muscarinic effect. This possible Ca(++) antagonist
      activity was investigated in Ca(++)-free conditions, with the inhibitory effect
      of the extract tested against contractions induced by externally administered
      Ca(++). Zo.Cr (0.1-0.3 mg mL(-1)), similar to verapamil (0.03-0.10 microM),
      shifted the contractions induced by externally administered Ca(++) to the right,
      thus suggesting an inhibitory interaction between Zo.Cr and voltage-operated
      Ca(++) channels. Zo.Cr (0.1-3.0 microg mL(-1)) also potentiated acetylcholine
      peak responses in stomach fundus, similar to physostigmine, a cholinesterase
      inhibitor. Zo.Cr, in an in-vitro assay, showed specific inhibition of
      butyrylcholinesterase (BuChE) rather than acetylcholinesterase enzyme. Different
      pure compounds of ginger also showed spasmolytic activity in stomach fundus, with
      6-gingerol being the most potent. 6-Gingerol also showed a specific anti-BuChE
      effect. This study shows a unique combination of muscarinic, possible Ca(++)
      antagonist and BuChE inhibitory activities of dried ginger, indicating its
      benefit in dementia, including Alzheimer's disease.

PMID- 18812032
TI  - Effect of hesperetin, a citrus flavonoid, on bacterial enzymes and carcinogen
      induced aberrant crypt foci in colon cancer rats: a dose-dependent study.
AB  - Hesperetin, an important bioactive compound in Chinese traditional medicine, has
      antioxidant and anticarcinogenic properties. Hesperetin is found in abundance in
      orange and grape juices (200-590 mg L(-1)) consumed in the daily diet. We have
      investigated the effect of different doses of hesperetin on faecal and colonic
      mucosal bacterial enzymes and aberrant crypt foci (ACF) in 1,2-dimethylhydrazine
      (DMH)-induced colon carcinogenesis in male Wistar rats. The rats were divided
      into six groups and were fed a modified pellet diet for 16 weeks. Group 1 served
      as control and group 2 received the modified pellet diet along with hesperetin
      (30 mg kg(-1)). The rats in groups 3-6 rats were given a weekly subcutaneous
      injection of DMH (20 mg kg(-1)) for the first four weeks. Hesperetin was
      supplemented orally at different doses (10, 20 or 30 mg kg(-1)) for a total of 16
      weeks. At the end of the experimental period all rats were killed. In DMH-treated
      rats, the activity of faecal and colonic mucosal bacterial enzymes, such as beta
      glucuronidase, beta-galactosidase, beta-glucosidase, nitroreductase, sulfatase
      and mucinase, were significantly elevated, but in rats supplemented hesperetin
      along with DMH the activity was significantly lowered (P < 0.05). The total
      number of aberrant crypts was significantly increased in unsupplemented DMH
      treated rats, while hesperetin supplementation to DMH-treated rats significantly
      reduced the total number of crypts. The results demonstrated that hesperetin
      supplementation at a dose of 20 mg kg(-1) played a potent role in suppressing the
      formation of aberrant crypt foci and reducing the activity of bacterial enzymes
      in colon cancer.

PMID- 18812033
TI  - Protective effects of total flavonoids of Bidens bipinnata L. against carbon
      tetrachloride-induced liver fibrosis in rats.
AB  - Bidens bipinnata L. is well known in China as a traditional Chinese medicine and
      has been used to treat hepatitis in clinics for many years. In a previous study
      we found that total flavonoids of Bidens bipinnata L. (TFB) had a protective
      effect against carbon tetrachloride (CCl4)-induced acute liver injury in mice.
      Now this study was designed to investigate its therapeutic effect against CCl4
      induced liver fibrosis in rats and to determine, in part, its mechanism of
      action. The liver fibrosis model was established by subcutaneous injection of 50%
      CCl4 twice a week for 18 weeks. TFB (40, 80 and 160 mg kg(-1)) was administered
      by gastrogavage daily from the 9th week. The results showed that TFB (80 and 160
      mg kg(-1)) treatment for 10 weeks significantly reduced the elevated liver index
      (liver weight/body weight) and spleen index (spleen weight/body weight), elevated
      levels of serum transaminases (alanine aminotransferase and aspartate
      aminotransferase), hyaluronic acid, type III procollagen and hepatic
      hydroxyproline. In addition, TFB markedly inhibited CCl4-induced lipid
      peroxidation and enhanced the activity of the antioxidant enzymes superoxide
      dismutase and glutathione peroxidase. Moreover, TFB (80 and 160 mg kg(-1))
      treatment improved the morphologic changes of hepatic fibrosis induced by CCl4
      and suppressed nuclear factor (NF)-kappaB, alpha-smooth muscle actin (SMA)
      protein expression and transforming growth factor (TGF)-beta1 gene expression in
      the liver of liver fibrosis of rats. In conclusion, TFB was able to ameliorate
      liver injury and protect rats from CCl4-induced liver fibrosis by suppressing
      oxidative stress. This process may be related to inhibiting the induction of NF
      kappaB on hepatic stellate cell activation and the expression of TGF-beta1.

PMID- 18812034
TI  - Reduced prehepatic extraction of nicardipine in the presence of pioglitazone in
      rats.
AB  - This study investigated the effect of pioglitazone on the pharmacokinetics of
      oral and i.v. nicardipine in rats. Pharmacokinetic parameters were determined
      after nicardipine was administered orally (12 mg kg(-1)) or i.v. (4 mg kg(-1))
      with or without a single dose of oral pioglitazone (0.3 or 1.0 mg kg(-1)).
      Compared with the control group given nicardipine alone, coadministration of
      pioglitazone significantly decreased the total plasma clearance of orally
      administered nicardipine (by 40.4-46.3%, P < 0.05) and significantly increased
      the area under the plasma concentration-time curve (by 81.8-96.3%) and the peak
      plasma concentration, C(max) (by 56.5-66.8%). T(max) and the terminal plasma half
      life of nicardipine were not affected, however. Coadministration of oral
      pioglitazone did not affect the pharmacokinetics of i.v. nicardipine, implying
      that pioglitazone may mainly decrease the prehepatic extraction of nicardipine
      during intestinal absorption. In conclusion, pioglitazone significantly enhanced
      the oral bioavailability of nicardipine in rats by reducing its presystemic
      clearance.

PMID- 18812035
TI  - Smoking cessation and tuberculosis: connecting the DOTS.

PMID- 18812036
TI  - TB in disasters.

PMID- 18812037
TI  - Strengthening laboratory services for today and tomorrow. Plenary Lecture given
      during the 38th Union World Lung Conference on Lung Health, Cape Town, South
      Africa, 8-12 November 2007.

PMID- 18812038
TI  - The design effect and cluster samples: optimising tuberculosis prevalence
      surveys.
AB  - Cross-sectional surveys of disease prevalence, including for tuberculosis (TB),
      often use a two (or more) stage sampling procedure. By choosing clusters of
      people randomly from all possible clusters, the logistic costs of doing the
      survey can be reduced. However, this increases the statistical uncertainty in the
      estimate of prevalence, and we need to balance the reduction in cost against the
      increase in uncertainty. Here we describe cluster sampling and consider ways to
      determine the optimal survey design as well as the extent to which deviations
      from the optimal design matter. We illustrate the results using data from a
      recent survey in Cambodia in which TB was diagnosed using sputum smears, cultures
      and X-rays.

PMID- 18812039
TI  - Change in the risk of tuberculous infection over an 8-year period among
      schoolchildren in Bangalore City.
AB  - SETTING: Bangalore City, South India. OBJECTIVE: To estimate the trends in
      transmission of tuberculous infection. METHODS: Two tuberculin surveys were
      carried out among children attending grades 1 and 2 of 60 selected schools at an
      interval of 8.3 years, corresponding to the period of DOTS expansion. Tuberculin
      testing was carried out using 1 tuberculin unit (TU) of purified protein
      derivative (PPD) RT 23 with Tween 80, and the maximum transverse diameter of
      induration was recorded about 72 h later. As the reactions due to infection with
      tubercle bacilli could not be clearly delineated from cross-reactions on the
      frequency distributions of tuberculin reaction sizes at either survey, the
      prevalence of tuberculin reactions > or = 10 mm, > or = 12 mm and > or = 14 mm in
      size were compared between the two surveys. The annual risk of tuberculous
      infection (ARTI) was computed from the estimated prevalence of reactions > or =
      14 mm in size. RESULTS: Estimates of prevalence of reactions at all chosen cut
      off points were lower at Survey II compared to Survey I. These differences were
      statistically significant. An average per annum decline in ARTI of about 4% was
      observed between the two surveys. CONCLUSION: Tuberculosis control measures
      should be further intensified to enhance the rate of decline in transmission of
      infection.

PMID- 18812040
TI  - Genetic diversity in clinical Mycobacterium tuberculosis isolates from Punjab.
AB  - SETTING: Two hospitals, Sri Guru Ram Das Institute of Medical Sciences and
      Research and the TB and Chest Hospital, Amritsar, Punjab. OBJECTIVE: To explore
      genetic diversity among the clinical Mycobacterium tuberculosis isolates
      prevalent in Punjab. DESIGN: Fifty-six random clinical isolates of M.
      tuberculosis were cultured from the sputum specimens of pulmonary tuberculosis
      patients. DNA was extracted from cultured biomass and analysed using the
      mycobacterial interspersed repetitive units (MIRU) typing method. RESULTS: MIRU
      typing of 51 isolates revealed 45 different patterns, with a combined Hunter
      Gaston discriminatory index (HGDI) of 0.990. Five clinical isolates failed to
      amplify for one or more MIRUs and were excluded from the analysis. The remaining
      isolates were categorised in three groups based on the allelic heterogeneity of
      individual MIRUs. MIRU 10, 16, 26 and 31 were highly discriminant, with an HGDI
      value >0.6; MIRU 4, 23, 24, 39 and 40 were designated as moderately discriminant
      (HGDI value 0.6-0.3) and MIRU 2, 20 and 27 were poorly discriminant (HGDI value
      <0.3). CONCLUSION: MIRU typing and the HGDI values revealed that M. tuberculosis
      strains from Punjab are genetically quite heterogeneous.

PMID- 18812041
TI  - The epidemiology of tuberculosis in Ottawa, Canada, 1995-2004.
AB  - BACKGROUND: In Ottawa (population 774,072), active tuberculosis (TB) cases are
      reported to Ottawa Public Health. There has been no comprehensive local
      epidemiological analysis to date. We report the epidemiology of TB in Ottawa and
      identify areas of improvement. METHODS: We reviewed TB cases reported to the
      Reportable Disease Information System from 1995 to 2004 to determine
      epidemiological characteristics, drug resistance, use of directly observed
      treatment (DOT) and rates of human immunodeficiency virus (HIV) co-infection.
      RESULTS: A total of 584 TB cases (79% foreign-born) were analyzed (average annual
      incidence 7.5/100,000). Anatomical site of disease followed national trends, with
      58% being pulmonary TB. DOT was applied in 49% of total cases. Culture results
      were available for 385 (66%) and resistance was found in 46 (12%) cases. HIV
      testing results were available for only 139 cases: 24% were positive. CONCLUSION:
      Overall, Ottawa TB rates are slightly higher than national rates, yet they
      reflect national trends. The surveillance data were imperfect, with poor or no
      recording of aboriginal origin, adverse events and treatment outcomes. Reported
      resistance patterns may be underestimated, as only 66% had cultures. HIV testing
      was underutilized. Given the high mortality with TB-HIV co-infection, testing
      should be routine. Correcting these limitations will improve surveillance data
      and TB control in the future.

PMID- 18812042
TI  - Treatment adherence of the latently infected tuberculosis population (post
      Katrina) at Wetmore TB Clinic, New Orleans, USA.
AB  - OBJECTIVES: To conduct a survey of the working of the Wetmore TB Clinic and to
      evaluate and analyze the follow-up data of the patient population diagnosed with
      latent TB infection (LTBI) at the Louisiana Office of Public Health (OPH) Region
      1 Wetmore TB Clinic. METHODS: This data analysis, initiated as a student
      practicum course, is based on a chart review of patients attending the Wetmore TB
      Clinic between 1 January 2006 and 30 June 2007. Only those patients with a
      diagnosis of LTBI were included in the survey. RESULT: The total survey
      population in this data analysis consisted of 380 LTBI patients. Results were
      analyzed for demographic data, TB risk factors, referral sources and treatment
      outcomes. Forty-three per cent of all the patients with LTBI displayed at least
      one of these risk factors. Adherence rates for LTBI treatment were low, at 19%.
      CONCLUSIONS: Post-Katrina New Orleans presents a challenging environment for TB
      control. This study forms a basis for further planning, provision and evaluation
      of services to this population. Its results and conclusions could be reflective
      of similar issues pertaining to public health TB clinics in other cities where
      displacement of patients, movement of migratory transient workers and disbanded
      infrastructure due to natural or man-made disasters could pose a problem.

PMID- 18812043
TI  - Smoking among tuberculosis patients in Kerala, India: proactive cessation efforts
      are urgently needed.
AB  - OBJECTIVES: To document smoking patterns among tuberculosis (TB) patients at
      eight different points of time before, during and after treatment, and to
      investigate the frequency and content of the quit smoking messages they received.
      DESIGN: A stratified random sample of 215 male TB patients from Kerala, India,
      who had completed treatment in the previous 9 months was surveyed using a pre
      tested semi-structured interview schedule. RESULTS: Six months prior to
      diagnosis, 94.4% of male TB patients were ever smokers and 71.2% were current
      smokers. Although 87% of patients had quit smoking soon after diagnosis, 36% had
      relapsed by 6 months post treatment. One third relapsed during the first 3 months
      of treatment and another third during the next 3 months of treatment. Two thirds
      of all smokers received cessation advice from primary care physicians, but less
      than half received advice from others. Less than half of all messages were TB
      specific; the rest were very general short instructions. Smoking more than 15
      cigarettes/bidis at the time of diagnosis was significantly associated with a
      lower quit rate during treatment (OR 8.0, 95%CI 2.1-30.9). CONCLUSION: Messages
      to not smoke often go unheeded among TB patients. Proactive efforts are needed to
      encourage health staff and DOTS providers to give strong cessation messages.

PMID- 18812044
TI  - Use of the QuantiFERON-TB Gold In-Tube test to monitor treatment efficacy in
      active pulmonary tuberculosis.
AB  - SETTING: Cohort study at a tertiary care hospital. OBJECTIVE: To assess the
      potential use of QuantiFERON-TB Gold In-Tube (QFT-G) in monitoring clinical
      response to anti-tuberculosis treatment. DESIGN: We conducted a cohort study of
      76 active pulmonary tuberculosis patients with serial testing by QFT-G at
      baseline and after 2 and 6 months of treatment. At these time points, we compared
      the performance of QFT-G with sputum culture status of the study subjects.
      RESULTS: Compared to baseline, 59 (77.6%) cases showed a decline whereas 17
      (22.4%) showed persistent or stronger interferon-gamma (IFN-gamma) responses at 2
      months. Using robust statistical methods, we observed that QFT-G assessment at 2
      months independently and significantly predicted the likelihood of remaining
      sputum culture-positive at the end of the intensive phase of anti-tuberculosis
      treatment. A higher IFN-gamma concentration by 1 international unit (IU)/ml
      corresponded to a 45% (95%CI 8-97) higher likelihood of failing to convert to a
      negative culture, whereas a rising or persistent IFN-gamma response was
      associated with a 17.3 (P = 0.007) times higher likelihood of remaining culture
      positive at 2 months. CONCLUSIONS: Our results suggest that QFT-G can potentially
      be used as a tool to monitor the efficacy of anti-tuberculosis treatment.

PMID- 18812045
TI  - Bodyweight gain to predict treatment outcome in patients with pulmonary
      tuberculosis in Peru.
AB  - SETTING: Tuberculosis control programmes of two health care centres in the
      central rainforest of Peru. OBJECTIVE: To evaluate if bodyweight gain (BWG)
      predicts treatment outcome in patients with pulmonary tuberculosis (PTB). DESIGN:
      Retrospective cohort study of adults with PTB diagnosed between 1995 and 2004.
      BWG was assessed after month 1 of treatment, after the initial phase and at the
      end of treatment. Patients were stratified into two BWG categories, < or = 5% and
      >5%. Failures and relapses were grouped together as unsuccessful treatment
      outcome. RESULTS: A total of 650 patients were included: 7.2% (n = 47) had an
      unsuccessful outcome. Unsuccessful outcome was associated with BWG < or = 5% at
      the end of treatment (RR 2.05, 95%CI 1.10-3.80), but not at the completion of
      month 1 (RR 0.99, 95%CI 0.52-1.88) or at completion of the initial phase (RR
      1.46, 95%CI 0.82-2.57). Median BWG at completion of the initial phase was higher
      in cured patients (P = 0.007). BWG < or = 5% at end of treatment (RR 2.35, 95%CI
      1.17-4.72), initial sputum smear 2+ (RR 2.48, 95%CI 1.14-5.31) and positive smear
      microscopy at month 2 (RR 4.0, 95%CI 1.30-12.31) were independent predictors of
      unsuccessful treatment outcome. CONCLUSION: BWG < or = 5% at the end of
      treatment, high bacterial load and lack of sputum conversion correlate with
      unsuccessful treatment outcome in this setting. New discriminative cut-offs for
      BWG are proposed.

PMID- 18812046
TI  - Factors contributing to treatment success among tuberculosis patients: a
      prospective cohort study in Bangkok.
AB  - SETTING: Chest Clinic, Ministry of Public Health and health care centres, Bangkok
      Metropolitan Administration. OBJECTIVE: To determine patient factors predicting
      successful tuberculosis (TB) treatment. DESIGN: A prospective cohort was
      conducted during May 2004 to November 2005. Newly diagnosed TB patients aged > or
      = 15 years were recruited after giving informed consent. Three sets of
      questionnaires were used to collect data from the patients three times. Data were
      also gathered from treatment cards. RESULTS: Of 1241 patients, 81.1% were
      successfully treated. Bivariate analysis indicated that patients' sex, education,
      occupation, level of knowledge about TB and adverse effects were associated with
      treatment success. Unconditional logistic regression analysis showed that females
      had a higher success rate than males (OR = 1.9, 95%CI 1.2-2.9). Patients with
      regular incomes had twice the likelihood of success of the unemployed (OR = 2.0,
      95%CI 1.1-3.5). Patients with high knowledge levels were more likely to complete
      treatment (OR = 2.0, 95%CI 1.2-3.4), while those with adverse effects were less
      likely to adhere (OR = 0.6, 95%CI 0.4-0.9). CONCLUSION: The current low treatment
      success rate may be partly due to inadequate knowledge about TB among patients.
      Improvements in health education and early detection and management of adverse
      effects should be prioritised by the National Tuberculosis Programme.

PMID- 18812047
TI  - Evaluating the effects of providing financial incentives to tuberculosis patients
      and health providers in China.
AB  - SETTING: A project was implemented in 50 low-income counties of Shanxi, where
      transport incentives were provided to poor patients for their first visit for
      tuberculosis (TB) diagnosis as well as for referral and supervision incentives
      for doctors. OBJECTIVE: To evaluate the effects of providing incentives on TB
      case detection and treatment. METHODS: A group of 51 control counties in Shanxi
      comparable to the intervention counties was selected. Routine TB reporting was
      reviewed at baseline (January-September 2004) and during the project period
      (January-September 2005) in both groups. A patient survey was conducted in two
      counties in each group, with interviews of 119 new smear-positive patients
      treated during the intervention. RESULTS: Patients who received travel incentives
      had an annual individual income similar to those who did not. The notification
      rates of new smear-positive cases improved in both groups; however, improvement
      was less marked in the intervention group (70%) than in the control group (99%).
      Travel incentives did not reduce patient and doctor delays in the intervention
      group compared with the control group (P > 0.05). CONCLUSION: Providing
      incentives was not effective in improving TB control. There are two possible
      reasons for this: the poor were not well-targeted due to a lack of operational
      tools, and more influential health systems issues were not addressed.

PMID- 18812048
TI  - Estimating the market for tuberculosis drugs in industrialized and developing
      nations.
AB  - BACKGROUND: The successful introduction of new drugs into low- and middle-income
      countries requires an understanding of the existing market size and market
      dynamics for the therapeutic area of interest. The drug markets in these
      countries are, however, less well understood than those in high-income countries.
      METHODS: The global market for tuberculosis (TB) drugs was estimated by studying
      in detail six high-burden countries and four high-income countries, followed by
      extrapolation. Data were derived from existing pharmaceutical audit databases and
      interviews with government officials, medical staff and suppliers. RESULTS: The
      use of qualitative inputs to inform the collection of quantitative information,
      notably to identify where the major flows of TB drugs are located, allowed a
      confident estimate of the global market for first-line TB drugs. Final ranges
      were US$261-316 million or US$310-418 million, depending on whether case
      notification rates or incidence were used for extrapolations. CONCLUSIONS: An
      estimation of the global TB drug market is made more reliable by a qualitative
      understanding of TB drug distribution pathways, which differ greatly among
      countries. The understanding of this structure in key high-burden countries
      provides the basis for a simpler update of the market estimate in the future.

PMID- 18812049
TI  - Treatment outcome and follow-up of multidrug-resistant tuberculosis patients,
      West Coast/Winelands, South Africa, 1992-2002.
AB  - SETTING: Brooklyn Chest Hospital, Western Cape, South Africa. OBJECTIVE: To
      evaluate the treatment outcome and 2- and 5-year follow-up of patients treated
      for multidrug-resistant tuberculosis (MDR-TB) with individualized regimens.
      DESIGN: Retrospective cohort study of all MDR-TB patients starting treatment
      during 1992-2002. Patients were evaluated every 6 months for 2 years after
      treatment and at 5 years when possible. RESULTS: Over 11 years, 491 (66%) of 747
      MDR-TB patients received treatment with two or more second-line drugs; 239 (49%)
      were cured or completed treatment, 68 (14%) died, 144 (29%) defaulted from
      treatment, 27 (5%) failed, 10 (2%) transferred out and 3 (<1%) remained on
      treatment. Only 176 (36%) were tested for human immunodeficiency virus and 15
      were positive. The proportion with a successful MDR-TB treatment outcome declined
      over time, while the proportion who defaulted remained stable. Among 410 patients
      who had not transferred out or died, 281 (69%) had 2-year data available: 185
      (66%) were cured or completed treatment, 32 (11%) were retreated for TB and 64
      (23%) died. CONCLUSIONS: Under program conditions in the West Coast/Winelands
      District, default rates were high and treatment success rates low. Outreach
      strategies for MDR-TB treatment should only be implemented if adequate resources
      are committed to the program.

PMID- 18812050
TI  - An outbreak of multidrug-resistant tuberculosis among refugees in Austria, 2005
      2006.
AB  - SETTING: In 2005-2006, the Austrian reference laboratory for tuberculosis (TB)
      identified multidrug-resistant (MDR) isolates from four cases of TB showing
      genotypes indistinguishable from each other. OBJECTIVE: To clarify the chain of
      transmission of this MDR-TB strain. DESIGN: An epidemiological case series
      investigation by reviewing TB notification reports and hospital discharge
      letters. RESULTS: The 38-year-old primary case of the MDR-TB cluster had
      initially been identified as a case of non-MDR pulmonary TB in June 2004, 7
      months after being detained for illegal immigration. In March 2005, he was lost
      to follow-up for 4 months. In June 2005, he presented with pulmonary and
      laryngeal TB due to MDR-TB. After discharge, the case was again lost to follow-up
      until April 2006, when he was readmitted with recurrent MDR-TB. A three-case
      cluster of pulmonary MDR-TB sharing the same strain as the primary case was
      detected in April 2006: the index case's 5-month-old daughter and a 25-year-old
      friend with a 6-month-old son. CONCLUSION: As MDR-TB has originated in the human
      immunodeficiency virus seronegative community in Austria, there is a clear need
      to implement national guidelines for the management of drug-resistant TB in
      Austria.

PMID- 18812051
TI  - Costs and cost-effectiveness of tuberculosis cultures using solid and liquid
      media in a developing country.
AB  - SETTING: The expansion of culture has been proposed to aid tuberculosis (TB)
      control in developing countries. OBJECTIVES: To examine the cost and cost
      effectiveness at the Zambian National TB Reference Laboratory of homemade and
      commercially produced Lowenstein-Jensen culture (HLJ and CLJ) as well as
      automated and manually read liquid culture (AMGIT and MMGIT). DESIGN: Costs were
      estimated from the provider's perspective and based on the average monthly
      throughput. Cost-effectiveness estimates were based on yield during the study
      period. RESULTS: All techniques show comparable costs per culture (between US$28
      and $32). Costs per Mycobacterium tuberculosis specimen detected were
      respectively US$197, $202, $312 and $340 for MMGIT, AMGIT, CLJ and HLJ. When
      modelled for the maximum throughput, costs were above US$95 per M. tuberculosis
      specimen detected for all techniques. When only performed among smear-negative
      specimens, costs per additionally identified M. tuberculosis would be US$487 for
      MMGIT and higher for other methods. CONCLUSION: Based on cost-effectiveness
      grounds, liquid media compare well with conventional solid media, especially
      where yield of MGIT is substantially higher than that of LJ media. The results
      indicate high overall costs per culture; the expansion of culture to
      decentralised levels with lower throughputs may result in even higher costs.

PMID- 18812052
TI  - Adenosine deaminase estimation and multiplex polymerase chain reaction in
      diagnosis of extra-pulmonary tuberculosis.
AB  - SETTING: Extra-pulmonary tuberculosis (EPTB), including mycobacteriosis,
      contributes 15-20% of all tuberculosis (TB) cases. The diagnosis of EPTB remains
      elusive because of the inadequate sensitivity of routine and conventional
      bacteriological methods for the detection of Mycobacterium tuberculosis and
      related organisms in clinical specimens such as cerebrospinal fluid (CSF),
      pleural fluid and peritoneal fluid. OBJECTIVE: To develop a better diagnostic
      marker for EPTB. DESIGN: In our study, 179 cases of EPTB were analysed for acid
      fast bacilli (AFB) smear, adenosine deaminase activity (ADA) and multiplex
      polymerase chain reaction (PCR). Although estimation of ADA is helpful, its
      sensitivity and specificity varies widely. On the other hand, a multiplex PCR
      using amplicons such as IS6110, dnaJ gene and hsp65 genes has high sensitivity
      (60-88%) and specificity (81-100%). RESULTS: On comparing AFB and ADA results
      with PCR, the PCR is clearly more effective than AFB (P < 0.001) and ADA
      estimation (P < 0.02) in CSF. The same result was observed with peritoneal fluid
      (P < 0.001 vs. P < 0.05) and pleural fluid (P < 0.001 and P < 0.05). CONCLUSION:
      The study shows that multiplex PCR remains the best tool and is a much better
      marker for diagnosing EPTB.

PMID- 18812053
TI  - Tuberculosis mimicked by melioidosis.
AB  - BACKGROUND: In regions endemic for tuberculosis (TB) such as India, presumptive
      anti-tuberculosis treatment is often prescribed. Melioidosis, caused by
      Burkholderia pseudomallei, is underdiagnosed in India, due to lack of awareness
      and a low index of suspicion. SETTING: A tertiary care hospital in south India.
      OBJECTIVE: To present our analysis of a series of 22 cases of suspected TB that
      was later confirmed as melioidosis. DESIGN: Twenty-two patients with culture
      proven melioidosis, who were initially given empirical anti-tuberculosis
      treatment, were retrospectively analysed regarding clinical presentation,
      laboratory findings and epidemiological features, with a view to determining any
      significant discriminatory parameter/s that would help distinguish the two
      diseases. RESULTS: Eight cases mimicked pulmonary TB, five tubercular arthritis,
      three tubercular spondylitis, two tubercular lymphadenitis, two splenic abscess,
      and one each mimicked tubercular pericarditis and parotid abscess. Fever was the
      chief presenting complaint; all had high erythrocyte sedimentation rate (ESR)
      values (mean 111 mm +/- 23.7 SD); 15 (68.2%) had neutrophilic leuco-cytosis, 20
      (90.9%) had diabetes mellitus. Subsequent to laboratory culture reports
      confirming melioidosis, appropriate treatment was instituted. CONCLUSION: Fever
      in a diabetic patient with high ESR and neutrophilic leucocytosis should raise
      suspicion of melioidosis while instituting presumptive anti-tuberculosis
      treatment in areas where both diseases are prevalent.

PMID- 18812054
TI  - Tuberculosis case definition: time for critical re-assessment?

PMID- 18812055
TI  - Methodological issues in estimating the annual risk of tuberculosis infection in
      Indonesia.

PMID- 18812056
TI  - Anti-aquaporin-4 antibodies in neuromyelitis optica: how to prove their
      pathogenetic relevance?
AB  - The discovery of a specific autoantibody response in neuromyelitis optica (NMO)
      patients, which selectively targets astrocytic end feet at the glia limitans1 and
      which is directed against the water channel aquaporin-4 (AQP-4)2 was a milestone
      in defining this disease entity and profoundly changed our view regarding its
      pathogenesis.3 Indirect evidence, coming from clinical observations and pathology
      strongly suggest that these autoantibodies play a major role in driving the
      disease process. The pathological hallmark of NMO lesions is a very selective and
      characteristic deposition of immunoglobulins and complement on astrocytes at the
      glia limitans, which is associated with destruction and loss of glial fibrillary
      acidic protein and AQP-4 positive astrocytes in fresh lesions4 to 6 followed by
      demyelination and global tissue destruction. As in other antibody-mediated
      diseases, granulocytes, and in particular eosinophils, are a major component of
      the inflammatory infiltrates.4 Furthermore, the distribution of the lesions in
      the brain and spinal cord of NMO patients correlates with the extent of regional
      AQP-4 expression.6,7 Most importantly, therapies, which eliminate antibodies
      (plasma exchange),8 or which target Blymphocytes (anti-CD20 antibodies),9 are at
      least in part effective in NMO patients. Based on this evidence NMO is now
      considered an antibody-mediated autoimmune disease, however, direct proof of the
      pathogenic potential of AQP-4 antibodies is so far lacking.

PMID- 18812057
TI  - 18th meeting of the European Neurological Society, Nice, France, 7 to 11 June
      2008.
AB  - Over 3200 neurologists attended the 18th Meeting of the European Neurological
      Society to participate in the exciting and highly scientific programe. There was
      a 19% rejection of the submitted abstracts which covered all the aspects of
      neurology. One major symposium, 27 oral presentations and 107 posters on multiple
      sclerosis (MS) were presented. Additionally, there were three teaching courses
      and one workshop on MS.

PMID- 18812058
TI  - Development of epithelia in experimental teratomas derived from rodent embryos.
AB  - Investigation of developmental potential of various embryonal tissues is
      important for design of new approaches to regenerative medicine aimed at
      supplementing tissues damaged by trauma or disease. Rodent embryos have been
      extensively used in experiments designed for investigation of developmental
      potential to give rise to various types of epithelia such as superficial
      epithelia, neuroepithelium and sometimes even malignantly transformed epithelium
      in teratoma-like structures. These experiments have been done in vitro, in
      transplants in vivo and by combined in vitro-in vivo methods.

PMID- 18812059
TI  - Thyroid autoimmunity in patients with alopecia areata.
AB  - Alopecia areata (AA) is a common form of localized, non-scarring hair loss. It is
      characterized by the loss of hair in patches, total loss of scalp hair (alopecia
      totalis), or total loss of body hair (alopecia universalis). The etiopathogenesis
      of the disease is still unclear, but there is evidence that autoimmunity and
      endocrine dysfunction may be involved. The aim of this study was to determine
      whether AA is statistically associated with thyroid autoimmunity. In this
      retrospective epidemiologic study, we compared the frequency of thyroid
      autoantibodies (thyroglobulin antibody, TgAb, and thyroid peroxidase antibody,
      TPAb) ATPO) in 70 AA patients and 30 healthy volunteers. Thyroid autoantibodies
      and thyroid hormones (thyroxine (T4), triiodothyronine (T3) and thyroid
      stimulating hormone (TSH)) were measured in all subjects. Thyroid functional
      abnormalities were found in 8 (11.4%) AA patients. Positive autoimmune antibodies
      were associated with AA in 18 (25.7%) patients, with no significant association
      between the disease severity and presence of these antibodies. The frequency of
      thyroid autoantibodies was significantly higher in AA patients than in healthy
      controls (25.7% vs. 3.3%; p<0.05). Our findings pointed to a significant
      association between AA and thyroid autoimmunity and showed the tests to detect
      thyroid autoantibodies to be relevant in AA patients.

PMID- 18812060
TI  - Principles of dermatologic ultrasound diagnostics.
AB  - Ultrasound is a valuable diagnostic tool widely used in medicine. Recently, high
      frequency ultrasonography has been introduced to dermatology owing to technical
      advances. Currently, the most often used frequency for skin imaging is between 20
      and 25 MHz. Ultrasound images can be generated in different modes, i.e. one
      dimensional A mode, two-dimensional B mode and C mode. This type of skin imaging
      is known as a noninvasive, reproducible and quantitative method, which can be
      used to evaluate skin characteristics in a variety of dermatologic diseases. It
      can found application in the assessment of skin tumors, morphea, psoriasis,
      lipodermatosclerosis, skin aging and photodamage, hypertrophic scars, wound
      healing processes and allergic reactions. Although skin ultrasonography and its
      clinical applications are still being explored, most probably it will be
      implemented in the routine dermatologic diagnosis in the forthcoming future.

PMID- 18812061
TI  - Eruptive acral lentigines--a new paraneoplastic sign?
AB  - Cutaneous signs may be the first indications of an internal disease. Any
      definitive sign of a neoplastic disease is of special importance since early
      diagnosis and early treatment may make a telling difference in improving
      prognosis. Presented is a 68-year-old patient with advanced stage melanoma that
      was associated with the appearance of multiple acral lentigines. The exact time
      course of onset of the lentigines in relation to the formation of the melanoma
      could not be established. However, from the information we could take out of our
      patient, it is clear that the lentigines had appeared either shortly before or
      after the appearance of the melanoma. In conclusion we suggest that the present
      case represents a new paraneoplastic sign.

PMID- 18812062
TI  - Fatal toxic epidermal necrolysis and severe granulocytopenia following therapy
      with cefuroxime.
AB  - Toxic epidermal necrolysis (TEN) is one of the most threatening adverse reactions
      to various drugs. No case of concomitant occurrence TEN and severe
      granulocytopenia following the treatment with cefuroxime has been reported to
      date. Herein we present a case of TEN that developed eighteen days of the
      initiation of cefuroxime axetil therapy for urinary tract infection in a 73-year
      old woman with chronic renal failure and no previous history of allergic
      diathesis. The condition was associated with severe granulocytopenia and followed
      by gastrointestinal hemorrhage, severe sepsis and multiple organ failure syndrome
      development. Despite intensive medical treatment the patient died. The present
      report underlines the potential of cefuroxime to simultaneously induce life
      threatening adverse effects such as TEN and severe granulocytopenia. Further on,
      because the patient was also taking furosemide for chronic renal failure, the
      possible unfavorable interactions between the two drugs could be hypothesized.
      Therefore, awareness of the possible drug interaction is necessary, especially
      when given in conditions of their altered pharmacokinetics as in case of chronic
      renal failure.

PMID- 18812063
TI  - Macular amyloidosis: a case report.
AB  - Macular amyloidosis is a major cause of skin pigmentation and a rare form of
      localized primary cutaneous amyloidosis in western countries, with a higher
      prevalence in Asia and South America. The etiopathogenesis of macular amyloidosis
      has not yet been fully clarified; a number of risk factors are involved, among
      them chronic friction in particular. A 54-year-old patient with macular
      amyloidosis is presented. The diagnosis of macular amyloidosis was based on
      history data on long-term persistence of the disorder, localized pruritus and
      constant scratching urge, grayish-brown pigmentation over the scapula, and
      detection of amyloid in histologic slides. Three-month tretinoin therapy resulted
      in pruritus alleviation, with no change in the appearance of hyperpigmentation.
      The exact incidence of macular amyloidosis in Croatia is not known, however, the
      issue appears to be underestimated or neglected in dermatology routine.

PMID- 18812064
TI  - Surgical treatment of lower limb ischemia and abdominal aorta aneurysm in a
      patient suffering from eosinophilic fasciitis.
AB  - We report on a 65-year-old woman with typical clinicopathologic features of
      eosinophilic fasciitis (Shulman syndrome) who suffered from lower limb ischemia
      and abdominal aorta aneurysm. Physical examination, laboratory data and
      histopathologic findings confirmed the diagnosis of eosinophilic fasciitis. The
      patient underwent aorto-bifemoral vascular prosthesis implantation. Tissue
      reactions associated with eosinophilic fasciitis produced serious disturbances of
      the implanted graft healing.

PMID- 18812065
TI  - Extensive atypical genital herpes simplex type 2 infection as an initial
      manifestation of acquired immune deficiency syndrome.
AB  - We present a case of an ulcerative lesion of the genitalia starting one year
      before in a 33-year-old man. Histopathologic examination revealed herpes virus
      infection, which suggested the existence of cell-mediated immunodeficiency. Human
      immunodeficiency virus (HIV) infection was confirmed by ELISA and Western blot
      test. The patient was treated with intravenous acyclovir, which led to complete
      remission. We underline the importance of early detecting and diagnosing patients
      with similar clinical manifestation as a sign of significant underlying
      immunodeficiency.

PMID- 18812066
TI  - Ancient medicine--a review.
AB  - Different aspects of medicine and/or healing in several societies are presented.
      In the ancient times as well as today medicine has been closely related to magic,
      science and religion. Various ancient societies and cultures had developed
      different views of medicine. It was believed that a human being has two bodies: a
      visible body that belongs to the earth and an invisible body of heaven. In the
      earliest prehistoric days, a different kind of medicine was practiced in
      countries such as Egypt, Greece, Rome, Mesopotamia, India, Tibet, China, and
      others. In those countries, "medicine people" practiced medicine from the magic
      to modern physical practices. Medicine was magical and mythological, and diseases
      were attributed mostly to the supernatural forces. The foundation of modern
      medicine can be traced back to ancient Greeks. Tibetan culture, for instance,
      even today, combines spiritual and practical medicine. Chinese medicine developed
      as a concept of yin and yang, acupuncture and acupressure, and it has even been
      used in the modern medicine. During medieval Europe, major universities and
      medical schools were established. In the ancient time, before hospitals had
      developed, patients were treated mostly in temples.

PMID- 18812067
TI  - Plasma cell infiltrate in common acquired melanocytic nevus.
AB  - The presence of plasma cells in melanocytic lesions has been considered in
      literature as a sign of concern, when evaluated in the appropriate context.
      Plasma cells have been evaluated in halo nevus, but they are not frequently
      reported in non-halo common acquired nevus. Our claim was to study how common and
      frequent plasma cells are in the latter type of nevi. Therefore, we examined 280
      of these nevi and selected the cases with an inflammatory infiltrate, even if
      mild. We then looked for plasma cells in the inflammatory infiltrate in the
      hematoxylin-eosin routine sections and selected 17 cases in which plasma cells
      (even if only occasional) could be found in the hematoxylin-eosin staining. Out
      of these 17, plasma cells were easily found in four cases, which were then
      further studied with immunohistochemistry for epithelial membrane antigen. The
      percentage of plasma cells varied in these four cases from 0.5% to 7%. No
      relation between the amount of plasma cells and either the location of the nevus
      or the location of the inflammatory infiltrate could be established. We conclude
      that the main point of this study is not to trust the presence of plasma cells as
      a solid criterion on its own, when evaluating a melanocytic lesion.

PMID- 18812068
TI  - Isfahan University Of Medical Sciences, Dermatology, Isfahan, April 28, 2008.

PMID- 18812069
TI  - The first two-day course on dermatoscopy in Croatia.

PMID- 18812070
TI  - Keynote from Japan. 5th Georg Rajka International Symposium on Atopic Dermatitis,
      Kyoto, May 11-13, 2008.

PMID- 18812071
TI  - Reminiscence on the Post IID 2008 Satellite International Meeting on Autoimmune
      Bullous Diseases. Otsu Prince Hotel, Japan, May 17-19, 2008.

PMID- 18812073
TI  - Naked mole-rat.

PMID- 18812074
TI  - Stereopsis.

PMID- 18812075
TI  - Robust long-term social memories in a paper wasp.

PMID- 18812076
TI  - Invasive pathogens threaten species recovery programs.

PMID- 18812077
TI  - Texture density adaptation and visual number revisited.

PMID- 18812079
TI  - Horizontal gene transfer and the evolution of cnidarian stinging cells.

PMID- 18812080
TI  - Motor proteins: myosin mechanosensors.
AB  - Mechanosensation is emerging as a general principle of myosin motors. As
      demonstrated in a recent study, the single-headed myosin I molecule is an
      exquisite mechanosensor, able to sense strain over a very small force range.

PMID- 18812081
TI  - Behavioural genetics: the social fly.
AB  - Two studies report the presence of a social influence on pheromonal communication
      in fruit flies, demonstrating that the production of pheromone blends and mating
      behaviour are profoundly influenced by social context.

PMID- 18812082
TI  - Chemotaxis: TorC before you Akt...
AB  - Chemotaxis uses intertwined signalling pathways, each individually dispensable.
      Recent work shows that Dictyostelium PKB/Akt can be spatially regulated
      independently of phosphatidylinositol (3,4,5)-trisphosphate via phosphorylation
      by TOR complex 2, placing this complex at the hub of chemotaxis.

PMID- 18812083
TI  - Mutualism: wasp keeps watchdogs to protect young.
AB  - The adaptive value of acarinaria - specialized structures in some wasps and bees
      that harbour symbiotic mites - has long been elusive. A new study has now shown
      that the mites are actually beneficial to their host by actively defending it
      against parasitoids.

PMID- 18812084
TI  - Hearing mechanics: a fly in your ear.
AB  - Recent work suggests that the auditory organ of Drosophila may serve as an
      excellent model system for understanding the complex mechanical signal processing
      that takes place in sensory hair cells of the vertebrate inner ear.

PMID- 18812085
TI  - Sporulation: SpoIIIE is the key to cell differentiation.
AB  - Sporulation in Bacillus subtilis requires asymmetric cell division, chromosome
      transfer into the spore and establishment of differential gene expression
      patterns. Several recent studies highlight the key roles of the SpoIIIE motor in
      this process.

PMID- 18812086
TI  - Cytoskeletal regulation: coordinating actin and microtubule dynamics in membrane
      trafficking.
AB  - The Arp2/3 complex is essential for actin nucleation and filament elongation in a
      variety of intracellular processes. This functional versatility is exerted
      through the regulation of its activity by nucleation-promoting factors (NPFs).
      The discovery of a new NPF, WHAMM, reveals unexpected connections between the
      actin and microtubule cytoskeletons and membrane dynamics during ER-to-Golgi
      transport.

PMID- 18812087
TI  - Biomechanical acclimation: flying cold.
AB  - Why are animals reared at colder temperatures larger? A new study shows that
      fruit flies reared at lower temperatures are better able to fly in the cold.

PMID- 18812088
TI  - Axonal domains: role for paranodal junction in node of Ranvier assembly.
AB  - A new study shows that communication between axons and glia at the paranodal
      junction can orchestrate the formation of the node of Ranvier.

PMID- 18812089
TI  - TRPs in our senses.
AB  - In the last decade, studies of transient receptor potential (TRP) channels, a
      superfamily of cation-conducting membrane proteins, have significantly extended
      our knowledge about the molecular basis of sensory perception in animals. Due to
      their distinct activation mechanisms and biophysical properties, TRP channels are
      highly suited to function in receptor cells, either as receptors for
      environmental or endogenous stimuli or as molecular players in signal
      transduction cascades downstream of metabotropic receptors. As such, TRP channels
      play a crucial role in many mammalian senses, including touch, taste and smell.
      Starting with a brief survey of sensory TRP channels in invertebrate model
      systems, this review covers the current state of research on TRP channel function
      in the classical mammalian senses and summarizes how modulation of TRP channels
      can tune our sensations.

PMID- 18812090
TI  - SHOC1, an XPF endonuclease-related protein, is essential for the formation of
      class I meiotic crossovers.
AB  - Crossovers (COs) are essential for the completion of meiosis in most species and
      lead to new allelic combinations in gametes. Two pathways of meiotic crossover
      formation have been distinguished. Class I COs, which are the major class of CO
      in budding yeast, mammals, Caenorhabditis elegans, and Arabidopsis, depend on a
      group of proteins called ZMM and rely on specific DNA structure intermediates
      that are processed to form COs. We identified a novel gene, SHOC1, involved in
      meiosis in Arabidopsis. Shoc1 mutants showed a striking reduction in the number
      of COs produced, a similar phenotype to the previously described Arabidopsis zmm
      mutants. The early steps of recombination, revealed by DMC1 foci, and completion
      of synapsis are not affected in shoc1 mutants. Double mutant analysis showed that
      SHOC1 acts in the same pathway as AtMSH5, a conserved member of the ZMM group.
      SHOC1 is thus a novel gene required for class I CO formation in Arabidopsis.
      Sequence similarity studies detected putative SHOC1 homologs in a large range of
      eukaryotes including human. SHOC1 appears to be related to the XPF endonuclease
      protein family, which suggests that it is directly involved in the maturation of
      DNA intermediates that lead to COs.

PMID- 18812091
TI  - Risk management in refractive lens exchange.

PMID- 18812092
TI  - Simultaneous phacoemulsification and DSEK in patients with concomitant cataract
      and bullous keratopathy due to Fuchs endothelial dystrophy.

PMID- 18812094
TI  - Long-term results of collagen crosslinking with riboflavin and UVA in
      keratoconus.

PMID- 18812096
TI  - Laboratory data and statistical evidence in fluoroquinolone study.

PMID- 18812098
TI  - Correlation between preoperative refraction and other variables.

PMID- 18812100
TI  - Consultation Section. Cataract surgical problem.

PMID- 18812110
TI  - Simple method for accurate alignment in toric phakic and aphakic intraocular lens
      implantation.
AB  - A simple technique for the accurate surgical alignment of toric phakic and
      aphakic intraocular lenses (IOLs) is described. The mathematical relationship
      between toric misalignment and cylinder error is reviewed to demonstrate the
      importance of toric lens alignment in the setting of increased rotational
      stability with newer generation lenses. A formula for calculating the exact lens
      misalignment given a manifest cylinder is also presented.

PMID- 18812111
TI  - Side-port stabilizer to assist implantation of microincision intraocular lenses.
AB  - We describe a new instrument for incision-assisted implantation of microincision
      intraocular lenses (IOLs). The instrument is a short nail, smooth and oval, that
      is inserted into the side-port incision to stabilize the eye during IOL
      implantation. The head prevents deep penetration and escape of the ophthalmic
      viscosurgical device through the incision. The instrument was safe and effective
      in its initial use; the 1 failure was due to the close proximity of the side port
      and the main incision.

PMID- 18812112
TI  - Combined phacoemulsification and transpupillary removal of heavy silicone oil.
AB  - We describe a technique for heavy silicone oil removal combined with
      phacoemulsification and intraocular lens insertion without scleral incisions or
      sutures using a modified 16-gauge cannula. The technique is less invasive than
      other techniques for removing silicone oil and does not interfere with the uveal
      tract or the peripheral retina.

PMID- 18812113
TI  - Retinal detachment after phacoemulsification in high myopia: analysis of 2356
      cases.
AB  - PURPOSE: To determine the incidence of and risk factors for rhegmatogenous
      retinal detachment (RD) in highly myopic eyes after cataract surgery. SETTING:
      Two ophthalmology centers in Munich and Ahaus, Germany. METHODS: This
      retrospective medical chart review comprised 1519 consecutive patients (2356
      eyes) with an axial length (AL) greater than 27.0 mm who had planned
      phacoemulsification and intraocular lens implantation in the capsular bag. In
      addition, all patients and/or the referring ophthalmologist were contacted
      regarding the occurrence of RD and laser capsulotomy and the date of occurrence.
      RESULTS: Follow-up was longer than 24 months in 84% of eyes. Because some cases
      of RD were questionably related to the preceding cataract surgery, the absolute
      incidence of postoperative RD was determined as highest (2.2%) and lowest (1.5%).
      Sex, history of laser capsulotomy, and increasing AL had no statistically
      significant effect on the rate of RD. The risk for postoperative RD was
      significantly higher in eyes of younger patients and eyes with preoperative
      prophylactic treatment for retinal degeneration. CONCLUSIONS: The risk for
      postoperative RD in this study (1.5% to 2.2%) corresponds to the incidence of
      pseudophakic RD and idiopathic RD in myopia described in the literature. The risk
      profile for postoperative RD in this series cannot be distinguished from the risk
      profile for idiopathic RD in myopia of this extent. The true effect of
      prophylactic treatment of degenerative lesions remains to be elucidated.

PMID- 18812114
TI  - Intraocular lens calculation after refractive surgery for myopia: Haigis-L
      formula.
AB  - PURPOSE: To describe the Haigis-L formula for the calculation of intraocular
      lenses (IOLs) after refractive laser surgery for myopia based on current biometry
      and keratometry and present clinical results. SETTING: University Eye Hospital,
      Wuerzburg, Germany, and various clinics and private practices. METHODS: The basic
      concepts of the new algorithm were described and summarized. The Haigis formula
      was analyzed with respect to its usability for eyes after laser surgery for
      myopia and modified accordingly. Correction curves for IOLMaster keratometry were
      derived from previous studies. The new formula was checked using the
      postoperative results of 187 cataract procedures in which 32 IOL types were
      implanted by 57 surgeons. Input data were current IOLMaster biometry as follows:
      axial length (AL), anterior chamber depth (ACD), and keratometry (corneal radii)
      measurements. RESULTS: Before IOL surgery, the mean spherical equivalent was 
      7.60 diopters (D)+/-3.90 (SD) (range -20.00 to -1.25 D); the mean AL, 27.02+/
      2.01 mm (range 23.09 to 35.32 mm); the mean ACD, 3.52 +/- 0.36 mm (range 2.43 to
      4.39 mm); and the mean of the measured corneal radii, 8.70+/-0.60 mm (range 7.28
      to 10.96 mm). The mean arithmetic refractive prediction error was -0.04+/-0.70 D
      (range -2.30 to +2.40 D) and the median absolute error, 0.37 D (range +0.01 to
      +2.40 D). The percentages of correct refraction predictions within +/-2.00, +/
      1.00, and +/-0.50 D were 98.4%, 84.0%, and 61.0%, respectively. CONCLUSIONS: The
      new formula would produce promising results in eyes without refractive history.
      Its refractive predictability fulfills the current criteria for normal eyes.

PMID- 18812115
TI  - Efficacy of topical plus intracameral anesthesia for cataract surgery in high
      myopia: randomized controlled trial.
AB  - PURPOSE: To assess the efficacy of intracameral lidocaine supplementation of
      topical anesthesia during cataract surgery in eyes with high myopia. SETTING:
      Department of Ophthalmology, Ospedale San Pietro-Fatebenefratelli, Rome, Italy.
      METHODS: This prospective double-blind study comprised 120 highly myopic eyes
      with an axial length (AL) greater than 26.0 mm scheduled for routine cataract
      surgery. Cases were divided into 2 groups of 60 eyes each. One group received a
      placebo of balanced salt solution (BSS) (control group) and the other group, a
      supplement of 0.1 mL preservative-free lidocaine hydrochloride 1% injected in the
      capsular bag during hydrodissection (lidocaine group). Intraoperative pain was
      assessed by recording spontaneous patient reports of sensation of pain or ocular
      discomfort during 3 surgical stages: phaco tip insertion, irrigation/aspiration
      (I/A) system insertion for cortical aspiration, I/A system insertion for
      ophthalmic viscosurgical device removal after intraocular lens implantation.
      Postoperative pain was assessed on a visual analog scale (range 0 to 10). Data
      were compared by chi-square and Mann-Whitney U tests. RESULTS: The overall mean
      AL was 28.58 mm (28.57 mm control group; 28.50 mm lidocaine group). Fewer
      patients in the lidocaine group reported intraoperative pain, ocular discomfort,
      or tissue manipulation (odds ratio=0.36; 95% confidence interval, 0.16-0.80; P=
      .019). The mean postoperative pain score was 1.88+/-2.17 (SD) in the control
      group and 1.36+/-2.02 in the lidocaine group; the difference was not
      statistically significant (P= .21). CONCLUSION: Intracameral lidocaine
      supplementation for cataract surgery may improve intraoperative comfort under
      topical anesthesia in highly myopic eyes.

PMID- 18812116
TI  - Tumor volume reduction using combined phacoemulsification and intravitreal
      triamcinolone injection for the management of cataract with treated uveal
      melanoma and atypical nevi.
AB  - PURPOSE: To study the reduction in tumor size and the safety and efficacy of
      combined phacoemulsification and intravitreal triamcinolone acetonide injection
      (phaco-IVTA) in patients with treated melanoma and atypical nevi. SETTING: Bascom
      Palmer Eye Institute, Miami, Florida, USA. METHODS: The medical records of 49
      consecutive patients (51 eyes) with treated melanoma or atypical nevi treated
      with phaco-IVTA were evaluated retrospectively for changes in Snellen visual
      acuity, tumor volume, and frequency of complications. Main outcome measures
      included a postsurgical change in tumor size greater than or equal to 0.5 mm of
      height or 1.0 mm of basal diameter by echographic analysis, improvement in visual
      acuity at 6 months and final follow-up, and complications including
      endophthalmitis, cystoid macular edema, epiretinal membrane, increased
      intraocular pressure, and persistent corneal edema. RESULTS: The median baseline
      visual acuity was 20/80 in the affected eye. At the 6-month follow-up
      examination, 13 (68%) of 19 eyes had achieved better than 20/40 visual acuity.
      Treated uveal melanomas (n=30) and atypical choroidal nevi (n=21) were stable
      with combined therapy, and echographic measurements improved in 12 eyes.
      Intraocular pressure increased from baseline to 25 mm Hg or more postoperatively
      in 4 of 51 eyes (8%). No other significant complications occurred. CONCLUSIONS:
      Combined phacoemulsification and IVTA was reasonably safe in patients with
      treated melanoma and atypical nevi. Tumors remained stable or decreased slightly
      in size. Intravitreal triamcinolone acetonide injection at the time of cataract
      surgery in patients with treated melanoma or nevus may reduce rates of tumor
      progression in these patients.

PMID- 18812117
TI  - Interim results of a compassionate-use clinical trial of Morcher iris diaphragm
      implantation: report 1.
AB  - PURPOSE: To evaluate the safety and efficacy of several different Morcher iris
      diaphragms in the treatment of partial or complete aniridia. SETTING: Jules Stein
      Eye Institute and the Department of Ophthalmology, David Geffen School of
      Medicine at UCLA, Los Angeles, California, USA. METHODS: This ongoing prospective
      single-site nonrandomized interventional clinical trial was designed to evaluate
      Morcher iris diaphragm models 50D, 50F, 96S, and 96F. Safety measures included
      changes in best corrected visual acuity (BCVA), surgical complications, adverse
      events, and postoperative interventions. Efficacy measures included changes in
      best corrected glare visual acuity and changes in daytime and nighttime glare
      sensitivity, measured by questionnaire responses. RESULTS: Thirteen patients (13
      eyes) completed a 1-year follow-up. Regarding safety, there was a statistically
      significant improvement in median BCVA of 2 Snellen lines (P= .002). One patient
      lost 2 letters of BCVA on the 20/20 line. There were 2 adverse events. One was
      minor bleeding during a posterior synechialysis that resolved without
      intervention. The second was piggyback intraocular lens decentration from
      worsening zonular dialysis in an eye with a trauma history. One postoperative
      intervention was the repositioning of a 50D ring. Regarding efficacy, there was a
      statistically significant median improvement in best corrected glare acuity of 10
      Snellen lines (P<or=.001). Subjective daytime glare improved 5 questionnaire
      scale points (P= .004), and nighttime glare sensitivity improved 3 scale points
      (P= .001). CONCLUSION: Morcher iris diaphragms were relatively safe and very
      effective in reducing the light and glare sensitivity associated with partial or
      complete aniridia.

PMID- 18812118
TI  - Effect of neodymium:YAG laser capsulotomy on retinal straylight values in
      patients with posterior capsule opacification.
AB  - PURPOSE: To determine the effect of neodymium:YAG (Nd:YAG) laser capsulotomy on
      retinal straylight values in patients with posterior capsule opacification (PCO).
      SETTING: Rotterdam Eye Hospital, Rotterdam, The Netherlands. METHODS: This
      prospective study comprised 35 patients with PCO scheduled to have Nd:YAG
      capsulotomy. Before and after Nd:YAG capsulotomy, the best corrected visual
      acuity (BCVA) was determined, a slitlamp examination was performed, and retinal
      straylight was measured. The straylight measurements were performed using the C
      Quant instrument utilizing the compensation-comparison method. Based on the
      median BCVA before Nd:YAG capsulotomy (20/50), patients were divided into 2
      groups: those with visual acuity better than 20/50 (good VA group) and those with
      an acuity of 20/50 or worse (poor VA group). RESULTS: The BCVA and straylight
      values improved significantly after Nd:YAG capsulotomy. The improvement in the
      straylight value was statistically significant in the good VA group and poor VA
      group. The BCVA and straylight values behaved independently from each other.
      Before capsulotomy, the BCVA and the straylight value were moderately correlated.
      After Nd:YAG capsulotomy, there was no significant correlation between the 2
      parameters. Also, the improvement in the 2 parameters after Nd:YAG capsulotomy
      was unrelated. CONCLUSIONS: After Nd:YAG capsulotomy, both BCVA and straylight
      values improved significantly. There was no uniform relation between BCVA and
      retinal straylight. Straylight must be considered an independent entry criterion
      for capsulotomy.

PMID- 18812119
TI  - Comparison of Collamer toric implantable [corrected] contact lens implantation
      and wavefront-guided laser in situ keratomileusis for high myopic astigmatism.
AB  - PURPOSE: To compare the postoperative visual outcomes after implantation of a
      Collamer toric implantable contact lens (ICL) and after wavefront-guided laser in
      situ keratomileusis in high myopic astigmatism. SETTING: Department of
      Ophthalmology, Kitasato University, Kanagawa, Japan. METHODS: This study
      comprised 30 eyes (18 patients) having toric ICL implantation and 24 eyes (17
      patients) having wavefront-guided LASIK (Technolas 217z) to correct high myopic
      astigmatism (manifest spherical equivalent [SE] <or=-6.0 diopters [D]; manifest
      refractive cylinder >or=1.0 D). The safety, efficacy, predictability, stability,
      and adverse events were assessed preoperatively and 1 week and 1, 3, and 6 months
      postoperatively. RESULTS: At 6 months, the mean safety index was 1.28+/-0.25 (SD)
      in the ICL group and 1.01+/-0.16 in the LASIK group and the mean efficacy index,
      0.87+/-0.15 and 0.83+/-0.23, respectively. All eyes in the ICL group and 71% of
      eyes in the LASIK group were within +/-1.00 D of the targeted SE correction at 6
      months. The mean change in manifest refraction from 1 week to 6 months was 
      0.04+/-0.24 D in the ICL group and -0.60+/-0.49 D in the LASIK group. There were
      no significant complications in the ICL group; 2 eyes (8.3%) in the LASIK group
      required enhancement ablations. CONCLUSION: Toric ICL implantation was better
      than wavefront-guided LASIK in eyes with high myopic astigmatism in almost all
      measures of safety, efficacy, predictability, and stability, suggesting that
      toric ICL implantation may become a viable surgical option to treat high myopic
      astigmatism.

PMID- 18812120
TI  - Anterior segment optical coherence tomography measurement of anterior chamber
      depth and angle changes after phacoemulsification and intraocular lens
      implantation.
AB  - PURPOSE: To use anterior segment optical coherence tomography (AS-OCT) to
      evaluate anterior chamber depth (ACD) and angle after phacoemulsification and
      intraocular lens (IOL) implantation. SETTING: Department of Ophthalmology,
      Yeditepe University, Istanbul, Turkey. METHODS: Forty-seven eyes (37 patients)
      had uneventful phacoemulsification and IOL implantation through a clear corneal
      incision. Anterior segment OCT was performed preoperatively and 1 week and 1
      month postoperatively. The angle-referenced (ACD(1)), pupil-referenced (ACD(2)),
      and lens-referenced (ACD(3)) ACDs, crystalline lens rise (CLR), pseudophakic
      posterior chamber depth (PPCD), and nasal and temporal iridocorneal angles were
      measured. Statistical analysis was by a 1-way analysis of variance and Pearson
      correlation analysis. RESULTS: The mean age of patients was 70 years+/-10.17
      (SD). The mean ACD(1) (mean increase) was 3.06+/-0.25 mm preoperatively, 3.16+/
      0.22 mm at 1 week (0.1 mm), and 3.16+/-0.19 mm at 1 month (0.1 mm); the mean
      ACD(2), 2.76+/-0.47 mm preoperatively, 3.62+/-0.24 mm at 1 week (0.86 mm), and
      3.63+/-0.20 mm (0.87 mm) at 1 month; and the mean ACD(3), 2.54+/-0.46 mm
      preoperatively, 3.97+/-0.28 mm at 1 week (1.43 mm), and 3.91+/-0.25 mm at 1 month
      (1.37 mm). The mean CLR was 0.497+/-0.363 mm and the mean PPCD, 0.322+/-0.150 mm.
      The increase in nasal and temporal iridocorneal angles was statistically
      significant at both postoperative examinations (P<.01). CONCLUSION: Deepening of
      the anterior chamber and widening of the nasal and temporal angles after cataract
      extraction was shown on AS-OCT.

PMID- 18812121
TI  - Negative dysphotopsia: long-term study and possible explanation for transient
      symptoms.
AB  - PURPOSE: To study the incidence, course, and common factors of patients with
      negative dysphotopsia and consider the possible role of the corneal incision in
      cases in which symptoms are transient. SETTING: Private practice and the
      University of Cincinnati, College of Medicine, Cincinnati, Ohio, USA. METHODS:
      Phacoemulsification with implantation of a single-piece acrylic intraocular lens
      (IOL) was performed in 250 consecutive routine cataract procedures. Patients were
      asked whether they noticed a temporal shadow on the day after surgery and were
      followed by serial evaluations for 3 years. Evaluations included subjective
      questionnaires and objective testing. RESULTS: The incidence of negative
      dysphotopsia was 15.2% on the first postoperative day, decreasing to 3.2% after 1
      year, then 2.4% after 2 and 3 years. Common findings included a shallow orbit,
      prominent globe, space greater than 0.45 mm between the iris and IOL by
      ultrasound biomicroscopy, and perimetric comet-shaped light in the area
      corresponding to the shadow. Slitlamp revealed a transparent peripheral capsule
      and a shadow sign in which a linear shadow on the iris became curvilinear as the
      light from the slit beam was projected through the incision toward the pupil.
      CONCLUSIONS: Two groups of patients experienced negative dysphotopsia that
      rapidly resolved or remained unchanged from the first postoperative day. It is
      hypothesized that the corneal edema associated with a beveled temporal incision
      contributes to transient negative dysphotopsia.

PMID- 18812122
TI  - Management of pseudophakic bullous keratopathy by combined Descemet-stripping
      endothelial keratoplasty and intraocular lens exchange.
AB  - PURPOSE: To evaluate visual recovery results in 11 patients with anterior
      pseudophakia and corneal endothelial dysfunction who had Descemet-stripping
      endothelial keratoplasty (DSEK) combined with anterior chamber intraocular lens
      (IOL) removal and scleral fixation of a posterior chamber IOL. SETTING:
      Department of Ophthalmology, District Railway Hospital Katowice, Katowice,
      Poland. METHODS: Eleven consecutive patients had DSEK combined with IOL exchange.
      Corneal transparency, central corneal thickness (CCT), endothelial cell density
      (ECD), visual outcomes, and complication rates were measured during the follow
      up. RESULTS: The mean age of patients was 76 years. All corneas remained clear
      during the mean 19.3-month follow-up. At the last visit, the mean uncorrected
      visual acuity was 0.16 (range 0.001 to 0.50) and the mean best corrected visual
      acuity, 0.36 (range 0.001 to 0.80). The mean spherical equivalent was +0.30
      diopter (D) (range -2.00 to +2.25 D) and the mean astigmatism, 2.20 D (range 1.25
      to 3.00 D). Three eyes with endothelial disk detachment required reinjection of
      air. Corneal rejection was observed in 1 eye 3 months postoperatively. Two eyes
      had flap erosion over the fixation suture. The mean CCT was 0.837 microm
      preoperatively and 0.605 microm postoperatively. The mean ECD was 3198
      cells/mm(2) in donor lenticules and 2048 cells/mm(2) at the last follow-up visit.
      Endothelial cell loss was 36%. CONCLUSION: Descemet-stripping endothelial
      keratoplasty combined with anterior chamber IOL replacement with a scleral
      fixated posterior chamber IOL was a safe method for the management of
      pseudophakic bullous keratopathy.

PMID- 18812123
TI  - Effect of intraoperative mitomycin-C on healthy corneal endothelium after laser
      assisted subepithelial keratectomy.
AB  - PURPOSE: To evaluate the effect of mitomycin-C (MMC) on corneal endothelial cells
      after laser-assisted subepithelial keratectomy (LASEK). SETTING: Department of
      Ophthalmology, Changzheng Hospital, Shanghai, China. METHODS: One hundred seventy
      four eyes of 89 patients who did not previously wear contact lenses were treated
      with LASEK with intraoperative use of topical MMC 0.02% (15 seconds). Noncontact
      corneal specular microscopy was performed in all eyes preoperatively and 1, 3,
      and 6 months after surgery. Preoperative pachymetry and ablation depth were
      measured in all eyes. Repeated-measures analysis of variance was used to compare
      the changes in the endothelial central cell density (CCD), coefficient of
      variation in cell size (CV), and percentage of hexagram cells (HEX) over time.
      Linear regression analysis was conducted to analyze the correlation between the
      change in the 3 corneal endothelium indices over time and the ablation depth and
      residual stroma bed (RSB) thickness. RESULTS: Preoperatively, the mean CCD was
      2755 cells/mm(2)+/-373 (SD), the mean CV was 31.45+/-8.26, and the mean HEX was
      66.03%+/-25.83%. After LASEK, there were no statistically significant changes in
      CCD, CV, or HEX (P>.05). Multiple linear regression did not identify ablation
      depth or RSB thickness as being predictive of a change in CCD, CV, or HEX
      (P>.05). CONCLUSION: The use of intraoperative topical MMC 0.02% for 15 seconds
      after LASEK did not affect the corneal endothelium.

PMID- 18812124
TI  - Cyclotorsion during laser in situ keratomileusis.
AB  - PURPOSE: To determine the magnitude of cyclotorsion during excimer laser ablation
      using a dynamic iris eye tracker. SETTING: Guy Hugh Chan Refractive Surgery
      Centre, Department of Ophthalmology, Hong Kong Sanatorium and Hospital, Hong
      Kong, China. METHODS: This retrospective study comprised 245 eyes (137 patients)
      that had laser in situ keratomileusis (LASIK) for myopia with or without
      astigmatism by the same surgeon. The magnitude of cyclotorsion during LASIK was
      recorded as the maximum, average, and minimum positions according to the angle of
      deviation displayed on the excimer laser computer screen. Measurements of
      cyclotorsion were performed during laser ablation. RESULTS: The mean total
      cyclotorsion was 2.181 degrees+/-1.392 (SD) (range 0.0 to 13.3 degrees). The mean
      average position (AP) was +0.134+/-1.851 degrees (range -7.0 degrees
      [excyclotorsion] to +12.6 degrees [incyclotorsion]). Forty-five eyes (18.4%) had
      an AP greater than +/-2 degrees, and 168 eyes (68.6%) deviated from the zero
      position at the onset of laser ablation. The mean incyclotorsion was 2.136+/
      1.440 degrees (78 eyes, 31.8%) and the mean excyclotorsion, 1.772+/-0.809 degrees
      (78 eyes, 31.8%). Eighty-six eyes (35.1%) had cyclotorsion in both directions
      (mixed cyclotorsion). The mean cyclotorsion was 2.670+/-1.588 degrees. Eight
      (3.3%) of the 109 patients having simultaneous bilateral LASIK had bilateral
      incyclotorsion or bilateral excyclotorsion. CONCLUSIONS: Cyclotorsion occurs
      before and during laser ablation. An active rotational eye tracker is fundamental
      to compensate for cyclotorsion and to enable greater precision in excimer laser
      ablation delivery.

PMID- 18812125
TI  - Corneal wavefront-guided photorefractive keratectomy in patients with irregular
      corneas after corneal refractive surgery.
AB  - PURPOSE: To evaluate the corrective potential of corneal wavefront-guided
      photorefractive keratectomy (PRK) in patients with high levels of corneal
      aberrations and symptoms after previous corneal refractive surgery. SETTING:
      Vissum-Instituto de Oftalmologico de Alicante, Alicante, Spain. METHODS: This
      study comprised 25 eyes (20 patients) that had 1 or more previous unsuccessful
      keratorefractive procedure. All eyes had PRK retreatment using the Esiris excimer
      laser and ORK-CAM software for customized ablation design. All eyes had a high
      preoperative level of corneal higher-order aberrations (HOAs) (coma-like or
      spherical-like root mean square [RMS] >0.5 microm). Changes in refractive
      outcomes, subjective symptoms, and corneal aberrometry were evaluated during a 6
      month follow-up. RESULTS: Uncorrected visual acuity improved significantly from
      preoperatively (mean 0.48) to 6 months after retreatment (mean 0.75) (P<.01). The
      mean best spectacle-corrected visual acuity (BSCVA) also improved significantly,
      from 0.78 to 0.90, respectively (P<.01). Forty-four percent of patients gained 1
      or more lines of BSCVA. The reduction in cylinder at 6 months was statistically
      significant (P= .01). Corneal aberrometry at 6 months showed a statistically
      significant reduction in total (P= .01), spherical-like (P<.01), coma-like (P=
      .02), and primary coma (P<.01) RMS. At 6 months, 72% of patients had low or no
      perception of halos and all reported no glare. CONCLUSION: Corneal wavefront
      guided PRK enhancement with the ORK-CAM system minimized corneal HOAs in eyes
      with previous unsuccessful keratorefractive surgery.

PMID- 18812126
TI  - Laser-assisted subepithelial keratectomy retreatment after laser in situ
      keratomileusis.
AB  - PURPOSE: To evaluate the efficacy and safety of laser-assisted subepithelial
      keratectomy (LASEK) retreatment after laser in situ keratomileusis (LASIK).
      SETTING: Mater Private Hospital, Dublin, Ireland. METHODS: In this retrospective
      study, 22 eyes of 20 patients had LASEK retreatment for residual refractive
      errors after LASIK. All patients who had the procedure between January 2004 and
      May 2007 were included in the study. The main outcome measures at the final
      follow-up visit were efficacy, predictability, safety, and stability. RESULTS:
      The mean spherical equivalent (SE) was -4.50 diopters (D)+/-2.88 (SD) (range 
      10.00 to +3.87 D) before LASIK and -1.23+/-0.95 D (range -2.50 to +2.00 D) after
      LASIK. The mean time between the initial LASIK procedure and LASEK enhancement
      was 56.2+/-24.3 months (range 6 to 84 months). The mean follow-up after
      retreatment was 6.68+/-6.47 months (range 3 to 24 months). At the final follow-up
      visit, 19 eyes (86.4%) had an uncorrected visual acuity of 20/30 or better and 17
      eyes (77.3%) were within +/-1.00 D of the target refraction. No patient lost more
      than 1 line of best corrected visual acuity or developed corneal haze greater
      than grade 1. CONCLUSION: Results indicate that LASEK retreatment after LASIK is
      a safe and effective alternative when LASIK retreatment is deemed unsafe because
      there is not sufficient residual corneal stromal bed or when retreatment is
      required many years after LASIK and relifting the original flap is expected to be
      problematic.

PMID- 18812127
TI  - Comparison and reproducibility of corneal thickness and curvature readings
      obtained by the Galilei and the Orbscan II analysis systems.
AB  - PURPOSE: To compare central corneal thickness (CCT) and keratometry readings
      using the Galilei dual Scheimpflug analyzer, the Orbscan II anterior segment
      analysis system, and the Sonogage ultrasound (US) pachymeter. SETTING: Lucerne
      Eye Clinic, Cantonal Hospital, Lucerne, Switzerland. METHODS: In a prospective
      single-center study, 85 eyes of 45 healthy volunteers were examined with the
      Orbscan II and Galilei systems in random order followed by Sonogage US
      pachymetry. The CCT and keratometry measurements were compared using a paired t
      test. To assess the intraobserver and interobserver reproducibility of the 2
      keratometers, 9 volunteers were examined 3 times by 4 independent observers and
      the intraclass correlation coefficient (ICC) was calculated. RESULTS: The mean
      CCT was 551.7 microm+/-36.6 (SD) with the Galilei, 554.8+/-45.1 microm with the
      Orbscan II, and 558.5+/-38.4 microm with the Sonogage. The CCT readings of the
      Galilei and Orbscan II did not differ significantly (P= .12). The mean
      keratometry readings with the Galilei and Orbscan II were similar, although both
      the steep (Ks) and flat (Kf) axes tended to be flatter with the Galilei system.
      The ICCs for CCT, Kf, and Ks were high with both keratometers (0.98, 0.97, 0.84
      for Galilei and 0.97, 0.96, 0.95 for Orbscan II, respectively), indicating that
      variation in measurements was mainly due to true subject-to-subject variation
      rather than observer error. CONCLUSION: Keratometry and pachymetry readings with
      the Galilei and Orbscan II systems showed good concordance and high
      reproducibility, which would allow the examinations to be delegated to nonmedical
      personnel.

PMID- 18812128
TI  - Incision sizes before and after implantation of SN60WF intraocular lenses using
      the Monarch injector system with C and D cartridges.
AB  - PURPOSE: To evaluate incision sizes for 6.0 mm optic hydrophobic acrylic
      intraocular lenses (IOLs) implanted with different injector systems and surgical
      techniques. SETTING: Department of Ophthalmology, Johann Wolfgang Goethe
      University, Frankfurt, Germany. METHODS: In this prospective randomized trial of
      100 cataract patients, hydrophobic acrylic IOLs (SN60WF) were implanted using 2
      injector systems with 2 cartridges (Monarch II and Monarch III with C and D
      cartridges, respectively; Alcon) and 2 surgical techniques (direct implantation
      and wound-assisted docking implantation). Incision sizes were measured before and
      after phacoemulsification as well as before and after IOL implantation using a
      Tsuneoka microincision gauge. The Saphiro-Wilks test was performed to detect
      nonparametric distribution and the Kruskal-Wallis test, to test for significant
      differences between groups. RESULTS: The mean incision sizes (mm) at the 4 points
      of treatment with the Monarch III with the D cartridge were 1.98+/-0.07, 2.01+/
      0.05, 2.42+/-0.07, and 2.51+/-0.05, respectively, with direct implantation and
      1.92+/-0.06, 1.98+/-0.04, 2.02+/-0.11, and 2.09+/-0.11, respectively, with wound
      assisted implantation. With the Monarch II with the C cartridge, the mean
      incision sizes were 2.17+/-0.06, 2.2+/-0.16, 2.77+/-0.11, and 2.86+/-0.11,
      respectively, with direct implantation and 2.12+/-0.10, 2.17+/-0.19, 2.19+/-0.09,
      and 2.28+/-0.08, respectively, with wound-assisted implantation. Postoperative
      incision sizes differed significantly from preoperative incision sizes and from
      each other (P<.05). CONCLUSION: With new injector systems and an appropriate
      docking implantation technique, foldable hydrophobic acrylic IOLs can be
      implanted through 2.0 mm tunnel incisions.

PMID- 18812129
TI  - Accuracy of preoperative biometry in vitrectomy combined with cataract surgery
      for patients with epiretinal membranes and macular holes: results of a
      prospective controlled clinical trial.
AB  - PURPOSE: To evaluate how adding vitrectomy to cataract surgery affects the
      accuracy of preoperative biometry and postoperative refractive outcomes. SETTING:
      Department of Ophthalmology, Ludwig Boltzmann Institute of Retinology and
      Biomicroscopic Lasersurgery, Rudolf Foundation Clinic, Vienna, Austria. METHODS:
      This study comprised 40 patients with vitreoretinal pathology and coexisting
      significant cataract (study group) and 40 patients with significant cataract only
      (control group). The main outcome measure was intraocular lens (IOL) power
      prediction error. Secondary outcome measures were spherical equivalent, anterior
      chamber depth, axial length, keratometry values, and intraocular pressure. A
      multivariate regression analysis was performed. RESULTS: There was a significant
      difference in prediction error between the study group and control group (P<
      .05). The addition of vitrectomy was associated with induced myopia of
      approximately -0.4 diopter, more so in patients who had epiretinal membrane
      removal than in patients with macular hole surgery (P= .04). There was no
      significant difference in prediction error between the 3 IOLs used (P= .2).
      CONCLUSION: The myopic shift was strongly dependent on the diagnosis and the need
      for intraocular tamponade, indicating that a slightly hyperopic IOL should be
      used in patients having combined surgery.

PMID- 18812130
TI  - Epi-laser in situ keratomileusis: comparative evaluation of epithelial separation
      with 3 microkeratomes.
AB  - PURPOSE: To evaluate the cleavage plane, corneal cytoarchitecture, and cell
      vitality of separated corneal epithelial sheets created with 3 commonly used
      microkeratomes. SETTING: Laboratories of the Regensburg University Medical
      Center, Regensburg, Germany. METHODS: Mechanical separation of the epithelial
      layer in 10 porcine eyes and 2 human eyes was performed with 3 different
      microkeratomes (Amadeus II, Zyoptix XP, Epivision). Five of 10 porcine corneas
      and the 2 human corneas treated with each microkeratome were processed for
      histology, electron microscopy, and immunohistochemistry. In 5 of 10 porcine
      corneas, the corneal epithelial sheets were separated from the globe and cell
      vitality was assessed with the trypan blue dye vitality test. RESULTS: A
      reproducible epithelial separation with a smooth surface was achieved in all
      eyes. The cleavage plane was located between the lamina lucida and the lamina
      densa. Damage to epithelial cells was mainly limited to the cut margins.
      CONCLUSIONS: Mechanical separation of the epithelial sheet in epithelial laser in
      situ keratomileusis (epi-LASIK) was safe and reproducible with all evaluated
      microkeratomes. Immunohistochemistry and electron microscopy showed the cleavage
      plane in epi-LASIK was between the basal epithelium and the basement membrane at
      the level of the lamina lucida.

PMID- 18812131
TI  - Calculating the optimal rotation of a misaligned toric intraocular lens.
AB  - PURPOSE: To present a formula for calculating the theoretical optimal position of
      a toric intraocular lens (IOL) that is rotationally misaligned. SETTING: Private
      practice in an academically affiliated setting. METHODS: Using equations for
      astigmatic decomposition, a formula to calculate the optimal rotation of an
      implanted toric IOL requiring only the power and axis of the IOL and the total
      eye astigmatism was derived. RESULTS: The optimal rotational position can be
      obtained from the derivation. CONCLUSION: The formula calculates the rotation an
      implanted toric IOL must undergo to minimize an eye's manifest astigmatism.

PMID- 18812132
TI  - Effect of lidocaine gel on povidone-iodine antisepsis and microbial survival.
AB  - PURPOSE: To determine whether the use of lidocaine gel prior to povidone-iodine
      antisepsis is associated with increased microbial survival. SETTING:
      Ophthalmology Department, Madigan Army Medical Center, Fort Lewis, Washington,
      USA. METHODS: A standardized suspension of Staphylococcus epidermidis was used to
      inoculate 5 blood agar plates that served as a control. A second group of 5 blood
      agar plates was inoculated, and then lidocaine gel was applied to the plates. A
      third group of 5 blood agar plates was inoculated, lidocaine gel was applied, and
      then povidone-iodine 5% was applied and allowed to cover the plates. A fourth
      group of 5 blood agar plates was inoculated, and then povidone-iodine 5% was
      allowed to cover the plates. Cultures of Staphylococcus aureus, Pseudomonas
      aeruginosa, and Haemophilus influenza were tested in a similar fashion. Microbial
      growth was evaluated after 24 hours. RESULTS: The number of colony forming units
      (CFUs) was similar in the control group and the S epidermidis, S aureus, and P
      aeruginosa lidocaine only and lidocaine with povidone-iodine groups. In these
      groups, each plate grew between 200 CFUs and 300 CFUs. In the Haemophilus
      influenza series, the lidocaine with povidone-iodine group had fewer CFUs than
      the control group. In all 4 series, the povidone-iodine only group had the least
      amount of CFUs, ranging from 0 to 6. CONCLUSIONS: The use of lidocaine gel before
      application of povidone-iodine 5% resulted in decreased effectiveness of
      antisepsis and increased microbial survivability. The increase in microbial
      survivability may increase the risk for postoperative infection in ocular surgery
      performed under topical anesthesia.

PMID- 18812133
TI  - Contribution of secreted proteases to the pathogenesis of postoperative
      Enterococcus faecalis endophthalmitis.
AB  - PURPOSE: To determine how a secreted protease contributes to the pathogenesis of
      post-cataract endophthalmitis caused by Enterococcus faecalis using an aphakic
      rabbit endophthalmitis model. SETTING: Department of Ophthalmology, Ehime
      University School of Medicine, Ehime, Japan. METHODS: The pathogenesis of E
      faecalis OG1S (secreted protease-positive) and E faecalis OG1X (secreted protease
      negative derivative of OG1S) was compared. After lens removal by
      phacoemulsification, either strain was inoculated into the lens bag. Changes in
      bacterial growth, electroretinography (ERG), and pathology of eyes were
      comparatively monitored throughout the course of the infection. Alternatively,
      culture fluid from either strain was injected into the vitreous body and ERG and
      pathology of the eyes were also examined. RESULTS: The levels of growth in the
      anterior chamber and vitreous cavity were similar for both strains. However,
      infection with OG1S resulted in a significantly greater reduction in ERG b-wave
      amplitude than OG1X. Histological examination showed that the posterior lens
      capsules were severely affected in eyes infected with OG1S, and inflammatory
      cells and cocci were found in the anterior vitreous cavity 24 hours after the
      infection. By 48 hours, the retina architecture was profoundly affected in eyes
      infected with OG1S. In contrast, few pathological changes were noted in the
      posterior lens capsules and retina of eyes infected with OG1X. Culture fluid in
      which OG1S had grown decreased ERG b-wave amplitude and caused morphological
      changes of the posterior capsule and retina similar to those in the infected eye.
      CONCLUSION: An extracellular protease plays a major role in the pathogenesis of E
      faecalis-induced postoperative endophthalmitis.

PMID- 18812134
TI  - New approach to evaluate retinal protection by intraocular lenses against age
      related lipofuscin accumulation-mediated retinal phototoxicity.
AB  - PURPOSE: To present a new approach for evaluating intraocular lenses (IOLs) for
      retinal protection from age-related lipofuscin accumulation-mediated
      phototoxicity. SETTING: Alcon Laboratories Inc., Fort Worth, Texas, USA, and
      Cardiff University, Cardiff, United Kingdom. METHODS: Age-related lipofuscin
      accumulation-mediated action spectra for retinal phototoxicity in an aphakic eye
      were created for this evaluation. Transmission curves for 6 IOLs and for cornea
      and spectral radiant power distribution for sunlight and 2 lamps were used.
      Pseudophakic action spectra and retinal phototoxicity for 3 wavelength ranges and
      3 ages were computed. The percentage protection of each IOL was computed as the
      reduction in phototoxicity relative to the aphakic eye. RESULTS: Retinal
      phototoxicity increased 3.66 times from the third to ninth decade of age. The
      comparative retinal phototoxicity and retinal protection provided by IOLs were
      dependent on the light source and range of wavelength; however, unlike
      phototoxicity, retinal protection was independent of age. The 420 to 480 nm range
      was the most useful for discriminating protection by IOLs. CONCLUSIONS: Retinal
      phototoxicity significantly increased with age; however, the retinal protection
      by IOLs was independent of age. The interaction between the transmission curve of
      IOLs and light sources required inclusion of widely used lamps besides sunlight
      for evaluation of IOLs. For the 420 to 480 nm wavelength range, the 3 light
      sources clearly discriminated the protection provided by IOLs. The AcrySof
      Natural IOL (Alcon) provided the highest protection consistently for the tested
      light sources.

PMID- 18812135
TI  - Long-term microstructural changes following epikeratophakia: in vivo confocal
      microscopy study.
AB  - The unilateral epikeratophakic eye of a 20-year-old woman with a history of
      congenital cataracts was examined using laser scanning in vivo confocal
      microscopy 17 years after transplantation. In vivo confocal microscopy
      demonstrated a reduced keratocyte density in the grafted lenticule and the host
      stroma, with unusual elongated and tortuous hyperreflective branching structures
      in the anterior stroma of the host cornea. The sub-basal nerve plexus was present
      in the lenticule, although with a reduced nerve density. The appearance of the
      host endothelium was similar to that observed in Fuchs endothelial dystrophy.
      Dramatic microstructural changes were observed in almost all layers of the cornea
      17 years after epikeratophakia. Although no longer performed as routine practice,
      in vivo confocal microscopy examination of epikeratophakia has provided
      fascinating insight into the potential corneal adaptations at a cellular level.

PMID- 18812136
TI  - Late postoperative capsular block syndrome versus liquefied after-cataract.
AB  - We report the case of a 76-year-old Chinese man who had uneventful cataract
      phacoemulsification and hydrophilic acrylic intraocular lens (IOL) implantation 6
      years previously. He presented with decreased vision; a homogeneous milky
      substance was found between the posterior chamber IOL and the posterior capsule
      without IOL displacement or a change in the refractive status. The milky
      substance was aspirated from the capsular bag. Biochemical analysis showed the
      concentrations of proteins and Ca(++) in the milky liquid were higher than those
      in the aqueous humor. Protein identification by mass spectrometry indicated that
      the milky liquid contained a high concentration of alpha-crystallin and beta
      crystallin.

PMID- 18812137
TI  - Anesthetic keratopathy after photorefractive keratectomy.
AB  - We report a case of anesthetic keratopathy after photorefractive keratectomy
      (PRK) and physician-prescribed topical anesthetic agents. After PRK for hyperopic
      correction, the patient was sent home with a bandage contact lens and
      instructions to use anesthetic eyedrops and take oral pain medications after
      surgery. During the first postoperative week, the eyes did not reepithelialize
      and bilateral perilimbal infiltrates developed. Cultures were negative and failed
      to clear with fortified antibiotic agents. On careful questioning, the patient
      admitted to instilling diluted tetracaine (0.05%) as needed in both eyes. She was
      instructed to stop the anesthetic agent labeled as "comfort drops" and the
      fortified antibiotics and start topical steroids. Soon after, the eyes
      reepithelialized and the infiltrates cleared. This case demonstrates the
      potential for anesthetic keratopathy in PRK patients.

PMID- 18812138
TI  - Methicillin-resistant Staphylococcus aureus endophthalmitis after
      phacoemulsification in a continuous ambulatory peritoneal dialysis patient.
AB  - We report a case of methicillin-resistant Staphylococcus aureus (MRSA)
      endophthalmitis after phacoemulsification in a continuous ambulatory peritoneal
      dialysis (CAPD) patient with a history of MRSA infection. This case raised the
      problem of preoperative identification and subsequent management of MRSA carrier
      status, which might reduce the risk for sight- or life-threatening infection.

PMID- 18812139
TI  - Intraocular lens power calculation after combination laser in situ keratomileusis
      and noncontact holmium:YAG laser thermal keratoplasty using Orbscan
      videokeratography.

PMID- 18812140
TI  - Exophiala jeanselmei keratitis after laser in situ keratomileusis.

PMID- 18812141
TI  - Advancing the ACR's agenda in Washington.

PMID- 18812142
TI  - When an express train becomes a local.

PMID- 18812143
TI  - Leadership development: insights from the military.

PMID- 18812144
TI  - The great internal threat to our specialty: the lack of a standardized board
      certifying examination in radiology.

PMID- 18812145
TI  - Commentary on "The great internal threat to our specialty: the lack of a
      standardized board-certifying examination in radiology".

PMID- 18812146
TI  - Decisions, decisions, decisions.

PMID- 18812147
TI  - Presidential address: distinction or extinction.
AB  - Despite its continuing scientific successes in imaging, radiology as a specialty
      is faced with a very difficult and competitive environment. Nonradiologists are
      more and more interested in vertically integrating imaging into their practices,
      while teleradiology and picture archiving and communication systems are resulting
      in the greater isolation of radiologists. Commoditization is a realistic and
      devastating threat to the survival and professionalism of the specialty. To
      remain viable as a specialty, radiologists must elevate their practice by
      subspecializing, becoming more involved with clinical care, and actively
      interacting with patients and referring clinicians. Distinction will prevent
      extinction.

PMID- 18812148
TI  - ACR white paper: the value added that radiologists provide to the health care
      enterprise.
AB  - Radiologists represent arguably one of medicine's least heralded but most
      important specialties. Although they carry sterling credentials as imaging and
      radiation safety experts, radiologists have lacked widespread public recognition.
      As public and private stakeholders cast an even more intense spotlight on
      imaging, the vital role of radiologists must be better understood. During the
      January 2008 ACR Forum on Future Practice Models for Radiology, participants and
      ACR leaders discussed the value added that radiologists bring to the health care
      enterprise and recommended that the ACR further study that topic. The ACR,
      dedicated to providing quality patient care since its inception in 1924, convened
      the Task Force on Value Added to address these issues. The task force determined
      the component stakeholders in the health care enterprise to whom value is added,
      defined the nature of the value for each constituent component, described the
      process of adding that value, and anticipated future trends that may affect the
      value proposition. Recommendations to the ACR for future action are offered.

PMID- 18812149
TI  - ACR Appropriateness Criteria on Hodgkin's lymphoma: favorable prognosis stage I
      and II.
AB  - The treatment for favorable-prognosis stage I and II Hodgkin's lymphoma has
      evolved over the past several years. Studies have attempted to reduce long-term
      treatment-related side effects, such as second malignancies and cardiac toxicity,
      through reduced chemotherapy or reduced radiotherapy. Randomized trials have
      compared radiation therapy alone with combined-modality therapy (chemotherapy
      followed by involved-field radiotherapy). Recent and ongoing trials have
      evaluated the optimal regimen and number of cycles of chemotherapy and the
      optimal radiotherapy dose and field size as part of combined-modality therapy, as
      well as the elimination of radiation therapy. Combined-modality therapy
      represents the current standard of care for most patients with favorable
      prognosis early-stage Hodgkin's lymphoma. Chemotherapy alone could also be an
      option for selected patients who are at low risk for relapse and high risk for
      late effects from radiotherapy. This article reviews recent and ongoing studies
      on treatment for favorable-prognosis early stage Hodgkin's lymphoma.
      Representative clinical cases are presented, with treatment recommendations from
      an expert panel of radiation oncologists and medical oncologists.

PMID- 18812150
TI  - Computers and the supply of radiology services: anatomy of a disruptive
      technology.
AB  - Over the next decade, computers will augment the supply of radiology services at
      a time when reimbursement rules are likely to tighten. Increased supply and
      slower growing demand will result in a radiology market that is more competitive,
      with less income growth, than the market of the past 15 years.

PMID- 18812151
TI  - Ethical trials to determine the risks and benefits of radiation exposure from
      coronary CT angiography.
AB  - This essay discusses the ethical implications of medical research using ionizing
      radiation in the diagnostic imaging range. Coronary CT angiography will be used
      as an example. Since coronary artery disease is the most common cause of death in
      the United States, any change in the work-up or management of patients with
      coronary artery disease has enormous clinical and economic implications. Risks of
      diagnostic radiation differ from those encountered in routine medical research as
      radiation-related cancers and heritable genetic damage can manifest in the
      irradiated individual or in subsequent generations. The risk to research subjects
      is ethically troubling because the research may not offer direct benefit to
      participants, although the benefits to society and future patients could be
      considerable. The American College of Radiology has a mandate to lead in the
      discussion of how to best minimize the risks of diagnostic radiation exposure in
      clinical research while encouraging studies likely to maximize benefits for
      future patients.

PMID- 18812152
TI  - Results and resident evaluation of the 2007 American College of Radiology in
      training examination in radiation oncology.
AB  - PURPOSE: To report the results, demographic data, and resident evaluation of the
      2007 ACR radiation oncology in-training (TXIT) examination. METHODS: The 2007
      TXIT examination consisted of 360 multiple-choice questions covering 13 different
      subject areas. It included 9 demographic questions and 7 evaluation items. Five
      hundred seventy-two residents from 85 institutions took the 2007 TXIT
      examination. RESULTS: The median raw score was 218.3 +/- 29 (range, 140-295). The
      mean item difficulty was 60.7%, with mean item discrimination of 0.19. The
      reliability coefficient was 0.92. Of the respondents to the demographic
      questions, 550 (96.2%), 493 (86.2%), and 402 (70.3%) residents had formal
      physics, biology, and clinical oncology instruction, respectively. Clinical
      experience was highest in breast, genitourinary, and lung cancers and lowest in
      soft-tissue sarcomas, pediatric tumors, and orbital neoplasms. Formal instruction
      in cancer biology, intensity-modulated radiation therapy, and statistics was
      reported by 416 (72.7%), 383 (67.0%), and 245 (42.8%) residents, respectively. On
      the basis of residents' responses to the evaluation questions, 31 (5.4%) did not
      know that the examination book was available to them after the test, 47 (8.2%)
      did not know that an answer key was available, and 79 (13.8%) residents did not
      know that rationales were available for future study. CONCLUSIONS: The
      reliability estimate for the ACR TXIT examination was high, typical of carefully
      constructed in-training examinations. The availability of the examination book,
      answer key, and rationales was not known by approximately 5% to 15% of residents
      taking the TXIT examination; therefore, a better method of informing the
      residents of these educational tools is needed.

PMID- 18812153
TI  - Automating radiologist workflow part 1: the digital consultation.
AB  - With the widespread adoption of picture archiving and communication systems and
      filmless imaging, ubiquitous and instantaneous access to imaging data has
      resulted in decreased radiologist-clinician consultations. It is therefore
      imperative that the radiology community develop new communication strategies to
      improve both the timeliness and the perceived value of the radiology report. One
      strategy to accomplish this goal is the creation of electronic consultation
      tools, which can effectively recreate radiologist workflow and the identification
      of key pathologic findings in an easy-to-use, well-organized, and timely fashion.
      This would be accomplished by recording radiologist-computer interactions using
      an electronic auditing tool, storing these interactions in an extensible markup
      language schema, which can subsequently be played back at a later point in time
      to recreate the radiologist consultation. This approach has the added benefits of
      allowing the radiologist to selectively edit content to the needs of different
      clinician users, index the comprehensive consultation into pathology-specific
      components, and perform asynchronous bidirectional consultations. This electronic
      consultation tool would result in the creation of context and user-specific
      consultation files, which can in turn be integrated with clinical data from
      electronic medical records.

PMID- 18812154
TI  - Your first 100 days: facing the challenge of becoming a new leader.

PMID- 18812155
TI  - The Wired for Health Care Quality Act: beyond HIPAA.

PMID- 18812156
TI  - Improving drug safety in radiology will require the adoption of new IT tools.

PMID- 18812157
TI  - Fusing images in radiation oncology procedures.

PMID- 18812158
TI  - Philip J. Hodes.

PMID- 18812159
TI  - Quantification of endogenous sirtuin metabolite O-acetyl-ADP-ribose.
AB  - Sirtuins are nicotinamide adenine dinucleotide (NAD(+))-dependent deacetylases
      that mediate cellular processes such as lifespan extension and metabolic
      regulation. Sirtuins form a unique metabolite, 2'-O-acetyl-ADP-ribose (OAADPr),
      shown to block oocyte maturation, bind to chromatin-related proteins, and
      activate ion channels. Given the various sirtuin phenotypes, the potential of
      OAADPr as a signaling molecule is extensive. However, exploration of the
      biological roles of OAADPr has been hindered by the lack of in vivo evidence and
      a reliable method for quantification. Here we provide the first direct evidence
      and quantification of cellular OAADPr. Compared with endogenous OAADPr levels
      (0.56+/-0.13 microM) in wild-type Saccharomyces cerevisiae, deletion of all five
      yeast sirtuins (Sir2 and Hst1-4) yielded essentially no detectable OAADPr. The
      single deletion of Hst2 yielded 0.37+/-0.12 microM OAADPr. Deletion of an enzyme,
      Ysa1, previously shown in vitro to hydrolyze OAADPr, resulted in a significant
      increase (0.85+/-0.24 microM) in OAADPr. Together, these data provide evidence
      that cellular levels of OAADPr are controlled by the action of sirtuins and can
      be modulated by the Nudix hydrolase Ysa1. Our methodology, consisting of internal
      standard (13)C-labeled OAADPr and liquid chromatography coupled to tandem mass
      spectrometry (LC-MS/MS) analysis, displays excellent sensitivity and a linear
      dynamic range from 0.2 to 500 pmol. Moreover, extraction efficiencies were
      greater than 75%. This methodology is an essential tool in probing the biological
      roles of OAADPr, especially under conditions in which sirtuin phenotypes are well
      established.

PMID- 18812160
TI  - Mediator-assisted simultaneous probing of cytosolic and mitochondrial redox
      activity in living cells.
AB  - This work describes an electron transfer mediator-assisted amperometric flow
      injection method for assessing redox enzyme activity in different subcellular
      compartments of the phosphoglucose isomerase deletion mutant strain of
      Saccharomyces cerevisiae, EBY44. The method is demonstrated using the
      ferricyanide-menadione double mediator system to study the effect of dicoumarol,
      an inhibitor of cytosolic and mitochondrial oxidoreductases and an uncoupler of
      the electron transport chain. Evaluation of the role of NAD(P)H-producing
      pathways in mediating biological effects is facilitated by introducing either
      fructose or glucose as the carbon source, yielding either NADH or NADPH through
      the glycolytic or pentose phosphate pathway, respectively. Respiratory
      noncompetent cells show greater inhibition of cytosolic menadione-reducing
      enzymes when NADH rather than NADPH is produced. Spectrophotometric in vitro
      assays show no difference between the cofactors. Respiratory competent cells show
      cytosolic inhibition only when NADPH is produced, whereas production of NADH
      reveals uncoupling at low dicoumarol concentrations and inhibition of complexes
      III and IV at higher concentrations. Spectrophotometric assays only indicate the
      presence of cytosolic inhibition regardless of the reduced cofactor used. This
      article shows the applicability of the amperometric method and emphasizes the
      significance of determining biological effects of chemicals in living cells.

PMID- 18812161
TI  - Transformation of real-time PCR fluorescence data to target gene quantity.

PMID- 18812162
TI  - Hic-5, an adaptor protein expressed in vascular smooth muscle cells, modulates
      the arterial response to injury in vivo.
AB  - Focal adhesion components are targets for biochemical and mechanical stimuli that
      evoke crucial injury. Hic-5 (hydrogen peroxide-inducible clone 5) is a
      multidomain adaptor protein which is implicated in the regulation of integrin
      signaling in focal adhesion. The aim of this research was to test the hypothesis
      that Hic-5, a focal adhesion LIM protein expressed in smooth muscle cells, is
      involved in dynamic processes by pathological stimuli in the vessel wall. Here,
      we describe the analysis of the function of Hic-5 using a mouse model of vascular
      injury that may mimic balloon angioplasty. At 4 days after vascular injury,
      marked down-regulation of the Hic-5 expression was observed in the smooth muscle
      layer, and local delivery of the Hic-5 using adenovirus vectors repressed injury
      induced neointimal expansion. In addition, Hic-5 reduced cells migration into
      three-dimensional collagen gels, and the forced expression of Hic-5 in cells
      embedded in the collagen gel matrix repressed the expression of uPA that
      participates in smooth muscle cell migration. These results suggest that Hic-5
      modulates cellular responses to pathological stimuli in the vessel wall.

PMID- 18812163
TI  - AMPKalpha2 counteracts the development of cardiac hypertrophy induced by
      isoproterenol.
AB  - As AMP-activated protein kinase (AMPK) controls protein translation, an anti
      hypertrophic effect of AMPK has been suggested. However, there is no genetic
      evidence to confirm this hypothesis. We investigated the contribution of
      AMPKalpha2 in the control of cardiac hypertrophy by using AMPKalpha2-/- mice
      submitted to isoproterenol. The isoproterenol-induced cardiac hypertrophy,
      measured by left ventricular mass and histological examination, was significantly
      higher in AMPKalpha2-/- than in WT animals. Moreover, the intensification of
      cardiac hypertrophy found in AMPKalpha2-/- mice can be linked to the abnormal
      basal overstimulation of the p70 ribosomal S6 protein kinase, an enzyme known to
      regulate protein translation and cell growth. In conclusion, this work shows that
      AMPKalpha2 plays a role of brake for the development of cardiac hypertrophy.

PMID- 18812164
TI  - Role of Gcn4 for adaptation to methylglyoxal in Saccharomyces cerevisiae:
      methylglyoxal attenuates protein synthesis through phosphorylation of eIF2alpha.
AB  - Methylglyoxal is a ubiquitous 2-oxoaldehyde derived from glycolysis. Although an
      endogenous metabolite, methylglyoxal at high concentrations has deleterious
      effects on cellular functions. Since pretreatment of Saccharomyces cerevisiae
      cells with methylglyoxal at a low concentration alleviates the toxicity of a
      subsequent lethal concentration of this 2-oxoaldehyde, proteins synthesized
      during treatment with methylglyoxal are necessary for adaptation to
      methylglyoxal. Nevertheless, here we show that methylglyoxal attenuates the rate
      of overall protein synthesis in S. cerevisiae. Phosphorylation of the alpha
      subunit of translation initiation factor 2 (eIF2alpha) is induced by several
      types of environmental stress, and subsequently, overall protein synthesis is
      reduced due to the impairment of the formation of a translation initiation
      complex. We found that methylglyoxal activates the protein kinase Gcn2 to
      phosphorylate eIF2alpha. The transcription factor Gcn4 is a master regulator of
      gene expression under conditions of amino acid starvation and some environmental
      stresses, the level of which is regulated by Gcn2. We found that adaptation to
      methylglyoxal was impaired in gcn4Delta cells, indicating the expression of
      certain genes regulated by Gcn4 to be important for the adaptive response to
      methylglyoxal.

PMID- 18812165
TI  - Interplant communication: airborne methyl jasmonate is essentially converted into
      JA and JA-Ile activating jasmonate signaling pathway and VOCs emission.
AB  - Methyl jasmonate (MeJA) was identified as an airborne signal involved in
      mediating interplant defense response communications over a decade ago. However,
      how MeJA activates plant defense systems and what becomes of the compound after
      it has done so has, thus far, remained unknown. To investigate this, Achyranthes
      bidentata plants were exposed to deuterated methyl jasmonate (d(2)MeJA) followed
      by absolute quantification of metabolic products of d(2)MeJA, and emissions of
      volatile organic compound (VOC) as defensive markers. We found that d(2)MeJA was
      metabolized mainly into deuterated jasmonic acid (d(2)JA) and jasmonoyl
      isoleucine (d(2)JA-Ile), and to a much lesser extent, deuterated jasmonoyl
      leucine (d(2)JA-Leu). Increases in d(2)JA-Ile/Leu and also endogenous JA-Ile/Leu
      were tightly co-related with, and significantly influenced the pattern and amount
      of, VOC emissions. The amount of accumulated d(2)JA-IIe was 13.1-fold higher than
      d(2)JA-Leu, whereas the amounts of JA-IIe and JA-Leu accumulated were almost
      identical. This study demonstrates that exogenous MeJA activates defensive
      systems (such as VOC emissions) in receiver plants by essentially converting
      itself into JA and JA-IIe and initiating a signal transduction leading to VOC
      emissions and induction of endogenous JA-IIe and JA-Leu, which in turn cause
      further amplification of VOC emissions.

PMID- 18812166
TI  - MUC1 intra-cellular trafficking is clathrin, dynamin, and rab5 dependent.
AB  - MUC1, a transmembrane glycoprotein, is abnormally over-expressed in most human
      adenocarcinomas. MUC1 association with cytoplasmic cell signal regulators and
      nuclear accumulation are important for its tumor related activities. Little is
      known about how MUC1 translocates from the cell membrane to the cytoplasm. In
      this study, live cell imaging was used to study MUC1 intracellular trafficking.
      The interaction between EGFR and MUC1 was mapped by FRET analysis and EGF
      stimulated MUC1 endocytosis was observed directly through live cell imaging. MUC1
      CT endocytosis was clathrin and dynamin dependent. Rab5 over-expression resulted
      in decreased cell membrane localization of MUC1, with accumulation of MUC1
      endocytic vesicles in the peri-nuclear region. Conversely, over-expression of a
      Rab5 dominant negative mutant (S34N) resulted in redistribution of MUC1 from the
      peri-nuclear region to the cytoplasm. Collectively, these results indicated that
      MUC1 intra-cellular trafficking occurs through a regulated process that was
      stimulated by direct EGFR and MUC1 interaction, mediated by clathrin coated pits
      that were dynamin dependent and regulated by Rab5.

PMID- 18812167
TI  - The macrophage-derived neutrophil chemotactic factor, MNCF: a lectin with TNF
      alpha-like activities on neutrophils.
AB  - The macrophage-derived neutrophil chemotactic factor (MNCF) is an alpha
      galactoside-binding lectin, known to induce dexamethasone-insensitive neutrophil
      recruitment. We further characterized MNCF effects on neutrophils and showed that
      it shares with TNF-alpha the ability to delay apoptosis and to trigger
      degranulation. MNCF and TNF-alpha effects show similar kinetics and involve Src
      kinases and MAPKinases dependent pathways. They were, however, clearly
      distinguished, since the soluble TNF-receptor etanercept prevented TNF but not
      MNCF effects, while melibiose disaccharide inhibited MNCF but not TNF effects.
      Absorption of MNCF on detoxi-gel did not alter its properties, precluding an LPS
      contamination effect. By contrast, galectin-3 required LPS to activate
      neutrophils. Specific antibodies allowed to further demonstrate that MNCF and
      galectin-3 are two distinct molecules. Finally, MNCF- and IL-8-induced neutrophil
      activation differed by their kinetic and sensitivity to pertussis toxin. In
      conclusion, MNCF is a distinct neutrophil agonist, with pro-inflammatory
      activities involving its carbohydrate recognition domain.

PMID- 18812168
TI  - Metal-enhanced fluorescence of single green fluorescent protein (GFP).
AB  - The green fluorescent protein (GFP) has emerged as a powerful reporter molecule
      for monitoring gene expression, protein localization, and protein-protein
      interaction. However, the detection of low concentrations of GFPs is limited by
      the weakness of the fluorescent signal and the low photostability. In this
      report, we observed the proximity of single GFPs to metallic silver nanoparticles
      increases its fluorescence intensity approximately 6-fold and decreases the decay
      time. Single protein molecules on the silvered surfaces emitted 10-fold more
      photons as compared to glass prior to photobleaching. The photostability of
      single GFP has increased to some extent. Accordingly, we observed longer duration
      time and suppressed blinking. The single-molecule lifetime histograms indicate
      the relatively heterogeneous distributions of protein mutants inside the
      structure.

PMID- 18812169
TI  - Wild-type p53 in cancer cells: when a guardian turns into a blackguard.
AB  - The tumor suppressor p53 controls a broad range of cellular responses. Induction
      of a transient (cell cycle arrest) or a permanent (senescence) block of cell
      proliferation, or the activation of cell death pathways in response to genotoxic
      stress comprise the major arms of the survival-death axis governed by p53. Due to
      these biological properties, inactivation of p53 is a crucial step in tumor
      development and progression, reflected by the high incidence of TP53 mutations in
      different types of human cancers. The remarkable potency of p53 in suppressing
      tumorigenic outgrowth has promoted the expectation that tumor cells expressing
      wild-type p53 (wtp53) should be more prone to elimination by cytotoxic treatments
      than tumor cells expressing mutant p53 (mutp53) with defunct wtp53 activities.
      However, recent findings yielded somewhat unexpected insights concerning the
      preponderance of the survival-promoting effects of wtp53 in cancer cells, a
      rather undesired property from the therapeutic point of view. In this commentary
      we will discuss the possibility that the developmentally established distinct
      patterns of wtp53 mediated responses in different tissues are an important factor
      in determining the ultimate outcome of cellular responses mediated by wtp53 in
      different types of tumor cells, with a particular focus on the divergent impact
      of wtp53 in malignant tumors of the central nervous system. We infer that a
      selective gain of pro-survival functions of wtp53 in cancer cells will confer a
      survival advantage that counteracts tumor therapy.

PMID- 18812170
TI  - Fitting a xenobiotic receptor into cell homeostasis: how the dioxin receptor
      interacts with TGFbeta signaling.
AB  - As our knowledge on the mechanisms that control cell function increases, more
      complex signaling pathways and quite intricate cross-talks among regulatory
      proteins are discovered. Establishing accurate interactions between cellular
      networks is essential for a healthy cell and different alterations in signaling
      are known to underline human disease. Transforming growth factor beta (TGFbeta)
      is an extracellular cytokine that regulates such critical cellular responses as
      proliferation, apoptosis, differentiation, angiogenesis and migration, and it is
      assumed that the latency-associated protein LTBP-1 plays a relevant role in
      TGFbeta targeting and activation in the extracellular matrix (ECM). The dioxin
      receptor (AhR) is a unique intracellular protein long studied because of its
      critical role in xenobiotic-induced toxicity and carcinogenesis. Yet, a large set
      of studies performed in cellular systems and in vivo animal models have suggested
      important xenobiotic-independent functions for AhR in cell proliferation,
      differentiation and migration and in tissue homeostasis. Remarkably, AhR activity
      converges with TGFbeta-dependent signaling through LTBP-1 since cells lacking AhR
      expression have phenotypic alterations that can be explained, at least in part,
      by the coordinated regulation of both proteins. Here, we will discuss the
      existence of functional interactions between AhR and TGFbeta signaling. We will
      focus on regulatory and functional aspects by analyzing how AhR status determines
      TGFbeta activity and by proposing a mechanism through which LTBP-1, a novel AhR
      target gene, mediates such effects. We will integrate ECM proteases in the AhR
      LTBP-1-TGFbeta axis and suggest a model that could help explain some in vivo
      phenotypes associated to AhR deficiency.

PMID- 18812171
TI  - AMPK activation by long chain fatty acyl analogs.
AB  - The antidiabetic efficacy of first-line insulin sensitizers (e.g., metformin,
      glitazones) is accounted for by activation of AMP-activated protein kinase
      (AMPK). Long chain fatty acids (LCFA) activate AMPK, but their putative
      antidiabetic efficacy is masked by their beta-oxidized or esterified lipid
      products. Substituted alpha,omega-dicarboxylic acids of 14-18 carbon atoms in
      length (MEDICA analogs) are not metabolized beyond their acyl-CoA thioesters, and
      may therefore simulate AMPK activation by LCFA while avoiding LCFA turnover into
      beta-oxidized or esterified lipid products. MEDICA analogs are shown here to
      activate AMPK and some of its downstream targets in vivo, in cultured cells and
      in a cell-free system consisting of the (alpha(1)beta(1)gamma(1))AMPK recombinant
      and LKB1-MO25-STRAD (AMPK-kinase) recombinant proteins. AMPK activation by MEDICA
      is accompanied by normalizing the hyperglycemia-hyperinsulinemia of diabetic
      db/db mice in vivo with suppression of hepatic glucose production in cultured
      liver cells. Activation of AMPK by MEDICA or LCFA is accounted for by (a)
      decreased intracellular ATP/AMP ratio and energy charge by the free acid, (b)
      activation of LKB1 phosphorylation of AMPK(Thr172) by the acyl-CoA thioester. The
      two activation modes are complementary since LKB1/AMPK activation by the CoA
      thioester is fully evident under conditions of excess AMP. MEDICA analogs may
      expand the arsenal of AMPK activators used for treating diabetes type 2.

PMID- 18812172
TI  - Pharmacology of 5HT(2C) receptor-mediated ERK1/2 phosphorylation: agonist
      specific activation pathways and the impact of RNA editing.
AB  - We have previously characterized a mechanism of 5HT-stimulated extracellular
      signal-regulated kinases 1 and 2 (ERK1/2) activation via the non-RNA-edited
      isoform of the serotonin 5HT(2C) receptor (5HT(2C)R-INI) in a CHO cell line. We
      have now used CV1 cells, which endogenously express epidermal growth factor
      receptors (EGFRs), to investigate whether the mechanisms underlying ERK1/2
      activation by the 5HT(2C)R change in a time-, agonist-, and cell background
      dependent manner. Interrogation of the CV1 5HT(2C)R-INI ERK1/2 signaling pathway,
      using a variety of pathway-selective inhibitors, revealed a clear time-dependence
      in the involvement of specific pathway components such as phosphatidylinositol 3
      kinase, EGFR, matrix metalloproteases and protein kinase C. The contribution of
      these components to the overall response also varied with the agonist used to
      stimulate the receptor, providing further evidence for the ability of 5HT(2C)R
      INI to signal in an agonist-specific manner. We also investigated the impact of
      5HT(2C)R RNA editing on this phenomenon. Although we found no alteration in
      antagonist pharmacology, the partially edited VSV and fully edited VGV isoforms
      of the 5HT(2C)R exhibited altered temporal and pharmacological characteristics,
      including the degree of dependence on specific effectors, in signaling to ERK1/2
      in comparison to the 5HT(2C)R-INI. In conclusion, we provide evidence for
      remarkable flexibility in 5HT(2C)R-mediated ERK1/2 signaling that can be
      pharmacologically and mechanistically distinct depending on the agonist or edited
      isoform involved and on the duration of receptor activation.

PMID- 18812173
TI  - An improved high-throughput dried blood spot screening method for Gaucher
      disease.

PMID- 18812174
TI  - Completing the family portrait of the anti-apoptotic Bcl-2 proteins: crystal
      structure of human Bfl-1 in complex with Bim.
AB  - Evasion of apoptosis is recognized as a characteristic of malignant growth. Anti
      apoptotic B-cell lymphoma-2 (Bcl-2) family members have therefore emerged as
      potential therapeutic targets due to their critical role in proliferating cancer
      cells. Here, we present the crystal structure of Bfl-1, the last anti-apoptotic
      Bcl-2 family member to be structurally characterized, in complex with a peptide
      corresponding to the BH3 region of the pro-apoptotic protein Bim. The structure
      reveals distinct features at the peptide-binding site, likely to define the
      binding specificity for pro-apoptotic proteins. Superposition of the Bfl-1:Bim
      complex with that of Mcl-1:Bim reveals a significant local plasticity of
      hydrophobic interactions contributed by the Bim peptide, likely to be the basis
      for the multi specificity of Bim for anti-apoptotic proteins.

PMID- 18812175
TI  - Critical amino acids for the 8(R)-dioxygenase activity of linoleate diol
      synthase. A comparison with cyclooxygenases.
AB  - 7,8-Linoleate diol synthase (7,8-LDS) of the take-all fungus and cyclooxygenases
      can be aligned with approximately 24% amino acid identity and both form a tyrosyl
      radical during catalysis. 7,8-LDS was expressed in insect cells with native 8R
      dioxygenase and hydroperoxide isomerase activities. We studied conserved residues
      of 7,8-LDS, which participate in cyclooxygenases for heme binding (His residues),
      hydrogen abstraction (Tyr), positioning (Tyr, Trp), and ionic binding of
      substrates (Arg). Site-directed mutagenesis abolished 8R-dioxygenase activities
      with exception of the putative distal histidine (His203Gln) and a tyrosine
      residue important for hydrogen bonding and substrate positioning (Tyr329Phe). The
      results demonstrate structural similarities between 7,8-LDS and cyclooxygenases.

PMID- 18812176
TI  - GATA4 is essential for jejunal function in mice.
AB  - BACKGROUND & AIMS: Although the zinc-finger transcription factor GATA4 has been
      implicated in regulating jejunal gene expression, the contribution of GATA4 in
      controlling jejunal physiology has not been addressed. METHODS: We generated mice
      in which the Gata4 gene was specifically deleted in the small intestinal
      epithelium. Measurements of plasma cholesterol and phospholipids, intestinal
      absorption of dietary fat and cholesterol, and gene expression were performed on
      these animals. RESULTS: Mice lacking GATA4 in the intestine displayed a dramatic
      block in their ability to absorb cholesterol and dietary fat. Comparison of the
      global gene expression profiles of control jejunum, control ileum, and GATA4 null
      jejunum by gene array analysis revealed that GATA4 null jejunum lost expression
      of 53% of the jejunal-specific gene set and gained expression of 47% of the set
      of genes unique to the ileum. These alterations in gene expression included a
      decrease in messenger RNAs (mRNAs) encoding lipid and cholesterol transporters as
      well as an increase in mRNAs encoding proteins involved in bile acid absorption.
      CONCLUSIONS: Our data demonstrate that GATA4 is essential for jejunal function
      including fat and cholesterol absorption and confirm that GATA4 plays a pivotal
      role in determining jejunal vs ileal identity.

PMID- 18812177
TI  - Identification of protein latent periodicities using recurrent correlation
      analysis.
AB  - Many large proteins have evolved by internal duplication and fusion. For proteins
      with internal structural symmetry, this means that their sequences should be made
      up of identical repeats. However, many of these repeat signals can only be seen
      at the structural level yet. We suggested a method of recurrent correlation
      analysis to detect the sequence repeats of proteins directly from their
      sequences. It showed that the internal repetitions of the representative proteins
      in six folds of mainly beta class could be identified directly at the sequence
      level.

PMID- 18812178
TI  - Exploitation of the derivatives of Dictyostelium differentiation-inducing factor
      1, which promote glucose consumption in mammalian cells.
AB  - AIMS: The differentiation-inducing factor-1 (DIF-1) is a signal molecule that
      induces stalk cell formation in the cellular slime mold Dictyostelium discoideum.
      DIF-1 has also been shown to possess pharmacological activities, such as the
      suppression of tumor cell growth and the promotion of glucose uptake in non
      transformed mammalian cells. In this study, we tried to develop compounds that
      possess weaker anti-tumor activity and stronger glucose uptake-promoting activity
      than DIF-1. MAIN METHODS: We investigated the in vitro effects of 12 derivatives
      of DIF-1 on glucose consumption in mouse 3T3-L1 cells and on cell growth in K562
      human leukemia cells. We also examined the effect of a good compound on the blood
      glucose concentration in KK-Ay diabetic mice. KEY FINDINGS: We found that some
      derivatives at 20 microM promoted glucose consumption more than twice as fast as
      the control. Of the derivatives, a compound named DIF-1(3M), which has a weaker
      anti-leukemic effect than DIF-1, promoted glucose consumption as strongly as DIF
      1 in confluent 3T3-L1 cells. While DIF-1 at 20 microM was inhibitory to the cell
      growth of 3T3-L1, DIF-1(3M) at 20 microM exhibited no inhibitory effect on the
      growing cells. We also found that DIF-1(3M) injected (10-12.5 mg/kg body weight)
      intraperitoneally in mice tended to lower the blood glucose concentration.
      SIGNIFICANCE: The present results open the possibility for the development of new
      agents that possess strong glucose-uptake-promoting activity but little anti
      tumor activity and may have therapeutic potential for the treatment of diabetes
      and/or obesity.

PMID- 18812179
TI  - Non-homologous end joining is the responsible pathway for the repair of
      fludarabine-induced DNA double strand breaks in mammalian cells.
AB  - Fludarabine (FLU), an analogue of adenosine, interferes with DNA synthesis and
      inhibits the chain elongation leading to replication arrest and DNA double strand
      break (DSB) formation. Mammalian cells use two main pathways of DSB repair to
      maintain genomic stability: homologous recombination (HR) and non-homologous end
      joining (NHEJ). The aim of the present work was to evaluate the repair pathways
      employed in the restoration of DSB formed following replication arrest induced by
      FLU in mammalian cells. Replication inhibition was induced in human lymphocytes
      and fibroblasts by FLU. DSB occurred in a dose-dependent manner on early/middle S
      phase cells, as detected by gammaH2AX foci formation. To test whether
      conservative HR participates in FLU-induced DSB repair, we measured the kinetics
      of Rad51 nuclear foci formation in human fibroblasts. There was no significant
      induction of Rad51 foci after FLU treatment. To further confirm these results, we
      analyzed the frequency of sister chromatid exchanges (SCE) in both human cells.
      We did not find increased frequencies of SCE after FLU treatment. To assess the
      participation of NHEJ pathway in the repair of FLU-induced damage, we used two
      chemical inhibitors of the catalytic subunit of DNA-dependent protein kinase (DNA
      PKcs), vanillin and wortmannin. Human fibroblasts pretreated with DNA-PKcs
      inhibitors showed increased levels of chromosome breakages and became more
      sensitive to cell death. An active role of NHEJ pathway was also suggested from
      the analysis of Chinese hamster cell lines. XR-C1 (DNA-PKcs-deficient) and XR
      V15B (Ku80-deficient) cells showed hypersensitivity to FLU as evidenced by the
      increased frequency of chromosome aberrations, decreased mitotic index and
      impaired survival rates. In contrast, CL-V4B (Rad51C-deficient) and V-C8 (Brca2
      deficient) cell lines displayed a FLU-resistant phenotype. Together, our results
      suggest a major role for NHEJ repair in the preservation of genome integrity
      against FLU-induced DSB in mammalian cells.

PMID- 18812180
TI  - Exploring the intramolecular phosphorylation sites in human Chk2.
AB  - A comparative biochemical analysis was performed using recombinant human protein
      kinase Chk2 (checkpoint kinase 2) expressed in bacteria and insect cells.
      Dephosphorylated, inactive, recombinant human Chk2 could be reactivated in a
      concentration-dependent manner. Despite distinct time-dependent
      autophosphorylation kinetics by monitoring the phosphorylation of amino acid
      residues T68, S19, S33/35, T432, in Chk2 wildtype and Chk2 mutants (T68A, T68D
      and Q69E) they gave identical specific activities. However, upon gel filtration
      of Chk2 wildtype and the mutants, only Chk2 wildtype and the T68D mutant led to
      the formation of a 'pure' dimer; dephosphorylated wildtype Chk2 eluted as a
      monomer. Transfection of HEK293 cells with Chk2 wildtype and Chk2 mutants in the
      absence or presence of DNA damage showed significant T68 phosphorylation already
      in the absence of DNA damaging reagents. Upon DNA damage, phosphorylation of
      additional Chk2 sites was observed (S19, S33/35). A comparison of ATM+/+ and ATM
      /- cells with respect to phosphorylation of residues T68, S19, S33/35 in the
      absence and presence of DNA damage showed in all cases phosphorylation of T68,
      although signal intensity was increased ca. three-fold after DNA damage. Mass
      spectrometric analyses of human recombinant Chk2 isolated from bacteria and
      insect cells showed distinct differences. The number of phosphorylated residues
      in human recombinant Chk2 isolated from bacteria was 16, whereas in the case of
      the recombinant human Chk2 from insect cells it was 8. Except for phosphorylated
      amino acid T378 which was not found in the Chk2 isolated from bacteria, all other
      phosphorylated residues identified in human Chk2 from insect cells were present
      also in Chk2 from bacteria.

PMID- 18812181
TI  - Quantification of aristolochic acid-derived DNA adducts in rat kidney and liver
      by using liquid chromatography-electrospray ionization mass spectrometry.
AB  - Aristolochic acid (AA), derived from the herbal genus Aristolochia and Asarum,
      has recently been shown to be associated with the development of nephropathy.
      Upon enzyme activation, AA is metabolized to the aristolactam-nitrenium ion
      intermediate, which reacts with the exocyclic amino group of the DNA bases via an
      electrophilic attack at its C7 position, leading to the formation of the
      corresponding DNA adducts. The AA-DNA adducts are believed to be associated with
      the nephrotoxic and carcinogenic effects of AA. In this study, liquid
      chromatography coupled with electrospray ionization mass spectrometry (LC-MS) was
      used to identify and quantify the AA-DNA adducts isolated from the kidney and
      liver tissues of the AA-dosed rats. The deoxycytidine adduct of AA (dC-AA) and
      the deoxyadenosine-AA adduct (dA-AA) were detected and quantified in the tissues
      of rats with one single oral dose (5mg or 30mg AA/kg body weight). The
      deoxyguanosine adduct (dG-AA), however, was detected only in the kidney of rats
      that were dosed at 30mg AA/kg body weight for three consecutive days. The amount
      of AA-DNA adducts found in the rats correlated well with the dosage.

PMID- 18812182
TI  - New A-nor steroids and their antifouling activity from the Chinese marine sponge
      Acanthella cavernosa.
AB  - A chemical examination of the Chinese sponge Acanthella cavernosa resulted in the
      isolation of three new A-ring contracted steroids, the ethyl esters of 2beta
      hydroxy-4,7-diketo-A-norcholest-5-en-2-oic acid (1), 24S-ethyl-2beta-hydroxy-4,7
      diketo-A-norcholest-5-en-2-oic acid (2), and 2beta-hydroxy-4,7-diketo-24R-methyl
      A-norcholest-5,22(E)-dien-2-oic acid (3), along with four other known steroids (4
      7). The structures were determined on the basis of extensive spectroscopic
      analysis. Compounds 1-3 showed antifouling activity toward the settlement
      inhibition of Balanus albicostatus with the EC(50) values of 8.2, 23.5, 31.6
      microg/mL, respectively.

PMID- 18812183
TI  - Assessment of protein phosphatase in a re-usable rapid assay format in detecting
      microcystins and okadaic acid as a precursor to biosensor development.
AB  - The feasibility of developing an immobilised protein phosphatase (PP) biosensor
      was tested by immobilising PP onto CNBr-activated Sepharose beads placed in
      Millipore microfilter plate wells. Under optimised immobilised enzyme assay
      conditions, okadaic acid (OA) and microcystin LR (MC-LR) inhibited Upstate
      Biotechnology PP (PP-2A), with IC50 values of 12.5 and 11nM respectively.
      Similarly, immobilised recombinant PP type 1 (rec PP-1) was inhibited by MC-LR
      and OA, with IC50 values of 150 and >1000nM respectively. The IC50 values for
      free PP-2A against OA and MC-LR were 2.5 and 3.5nM, and 0.7nM and 200nM for rec
      PP-1 against the same substrates respectively. For free and immobilised Neptunea
      arthritic PP (PP-2Ana) against OA the IC50 values were 0.45 and >1000nM
      respectively. Of the three immobilised enzyme systems, PP-2A showed greatest
      sensitivity to OA and MC-LR followed by rec PP-1 and PP-2Ana. In assessments for
      re-usability (determined by removal of > or =70% OA or MC-LR inhibition of PP-2A
      by washing), <50% of the original activity remained after 20 washings. Including
      1M NaCl in the wash buffer did not increase enzyme activity with wash frequency,
      but rather "salted in" the inhibitor. The LoD of immobilised PP-2A to MC-LR meets
      the WHO guideline of 1microgl(-1) for drinking water, and the sensitivity to OA
      (3.5microgl(-1)) would allow detection of DSP during the peak of some
      phytoplankton blooms.

PMID- 18812184
TI  - Ratio of lethal and edema factors in rabbit systemic anthrax.
AB  - Bacillus anthracis secretes two binary toxins: lethal toxin (PA + LF) and edema
      toxin (PA + EF) that play a major role in the pathogenesis of anthrax. Their
      activities can synergize or interfere among each other, depending on the cell
      type. It is therefore fundamental to know their concentration ratio in vivo.
      Here, we report the first determination of the concentration ratio of anthrax
      toxin components LF/EF in the serum of rabbits infected with B. anthracis spores.

PMID- 18812185
TI  - Human XPF controls TRF2 and telomere length maintenance through distinctive
      mechanisms.
AB  - XPF-ERCC1, a structure-specific endonuclease, is involved in nucleotide excision
      repair, crosslink repair and homologous recombination. XPF-ERCC1 is also found to
      interact with TRF2, a duplex telomeric DNA binding protein. We have previously
      shown that XPF-ERCC1 is required for TRF2-promoted telomere shortening. However,
      whether XPF-ERCC1 by itself has a role in telomere length maintenance has not
      been determined. Here we report that overexpression of XPF induces telomere
      shortening in XPF-proficient cells whereas XPF complementation suppresses
      telomere lengthening in XPF-deficient cells. These results suggest that XPF-ERCC1
      can function as a negative mediator of telomere length maintenance. In addition,
      we find that introduction of wild type XPF into XPF-deficient cells leads to over
      40% reduction in TRF2 association with telomeric DNA, indicating that XPF-ERCC1
      negatively regulates TRF2 binding to telomeric DNA. Furthermore, we show that XPF
      carrying mutations in the conserved nuclease domain fails to control TRF2
      association with telomeric DNA but it is competent for modulating telomere length
      maintenance. These results imply that XPF-ERCC1 controls TRF2 and telomere length
      maintenance through two distinctive mechanisms, with the former requiring its
      nuclease activity. Our results further imply that TRF2 association with telomeres
      may be deregulated in cells derived from XPF patients.

PMID- 18812187
TI  - Role of loops in the guanine quadruplex formation by DNA/RNA hybrid analogs of
      G4T4G4.
AB  - CD spectroscopy, gel electrophoresis and absorption-based thermal stability were
      used to analyze quadruplex formation of RNA and RNA/DNA hybrid analogs of the
      deoxyoligonucleotide G4T4G4, which forms a well-characterized basket-type
      quadruplex. All RNA-containing dodecamers, g4u4g4, G4u4G4 and g4T4g4 (RNA lower
      case, DNA capital letters), formed parallel, namely tetramolecular quadruplexes
      in Na+-containing solutions. The u4 loop forced DNA tetrads into the same
      conformation as adopted by g4u4g4. In contrast, the T4 loop destabilized the RNA
      tetrads. Potassium ions markedly stabilized parallel quadruplexes of RNA
      containing analogs as well as their bimolecular folding. In the presence of K+,
      g4T4g4 formed exclusively bimolecular quadruplexes of both parallel and
      antiparallel types as indicated by CD. Thus, the T4 loop permits RNA strands to
      adopt an antiparallel arrangement. These findings may be useful for engineering
      particular quadruplex foldings in different quadruplex-forming sequences.

PMID- 18812188
TI  - Rheological investigation on hyaluronan-fibrinogen interaction.
AB  - This paper concerns the interaction between hyaluronan and fibrinogen as model
      for protein-polysaccharide interaction. From rheological investigation, it is
      shown that a 3D physical network is promoted by mixing the two components; the
      mechanism is attributed to electrostatic interactions. The influences of the
      molecular weight and of the hyaluronan concentration are examined; the loose
      interaction obtained for addition of small amount of soluble protein induces a
      non-Newtonian behaviour which may be in direct relation with the behaviour
      observed previously on synovial fluids.

PMID- 18812186
TI  - Structure, function, and post-translational regulation of the catalytic and
      modifier subunits of glutamate cysteine ligase.
AB  - Glutathione (GSH) is a tripeptide composed of glutamate, cysteine, and glycine.
      The first and rate-limiting step in GSH synthesis is catalyzed by glutamate
      cysteine ligase (GCL, previously known as gamma-glutamylcysteine synthetase). GCL
      is a heterodimeric protein composed of catalytic (GCLC) and modifier (GCLM)
      subunits that are expressed from different genes. GCLC catalyzes a unique gamma
      carboxyl linkage from glutamate to cysteine and requires ATP and Mg(++) as
      cofactors in this reaction. GCLM increases the V(max) and K(cat) of GCLC,
      decreases the K(m) for glutamate and ATP, and increases the K(i) for GSH-mediated
      feedback inhibition of GCL. While post-translational modifications of GCLC (e.g.
      phosphorylation, myristoylation, caspase-mediated cleavage) have modest effects
      on GCL activity, oxidative stress dramatically affects GCL holoenzyme formation
      and activity. Pyridine nucleotides can also modulate GCL activity in some
      species. Variability in GCL expression is associated with several disease
      phenotypes and transgenic mouse and rat models promise to be highly useful for
      investigating the relationships between GCL activity, GSH synthesis, and disease
      in humans.

PMID- 18812189
TI  - Apigenin, a dietary flavonoid, sensitizes human T cells for activation-induced
      cell death by inhibiting PKB/Akt and NF-kappaB activation pathway.
AB  - Resistance of T cells to activation-induced cell death (AICD) is associated with
      autoimmunity and lymphoproliferation. We found that apigenin (4',5,7
      trihydroxyflavone), a non-mutagenic dietary flavonoid, augmented both extrinsic
      and intrinsic pathways of apoptosis in recurrently activated, but not in
      primarily stimulated, human blood CD4+ T cells. Apigenin potentiated AICD by
      inhibiting NF-kappaB activation and suppressing NF-kappaB-regulated anti
      apoptotic molecules, cFLIP, Bcl-x(L), Mcl-1, XIAP and IAP, but not Bcl-2.
      Apigenin suppressed NF-kappaB translocation to nucleus and inhibited IkappaBalpha
      phosphorylation and degradation in response to TCR stimulation in reactivated
      peripheral blood CD4 T cells, as well as in leukemic Jurkat T cell lines. Among
      the pathways that lead to NF-kappaB activation upon TCR stimulation, apigenin
      selectively inhibited PI3K-PKB/Akt, but not PKC-theta activation in the human T
      cells, and synergized with a PI3K inhibitor to markedly augment AICD. Apigenin
      also suppressed expression of anti-apoptotic cyclooxygenase 2 (COX-2) protein in
      activated human T cells, but it did not affect activation of Erk MAPKinase. Thus,
      in chronically activated human T cells, relatively non-toxic apigenin can
      suppress anti-apoptotic pathways involving NF-kappaB activation, and especially
      cFLIP and COX-2 expression that are important for functioning and maintenance of
      immune cells in inflammation, autoimmunity and lymphoproliferation.

PMID- 18812190
TI  - Generation and characterization of an H5N1 avian influenza virus hemagglutinin
      glycoprotein pseudotyped lentivirus.
AB  - An H5N1 avian influenza virus (AIV) hemagglutinin (HA) protein pseudotyped
      lentivirus, HIV/H5-HA, was generated, characterized in vitro and evaluated for
      its ability to induce protective immunity against virulent wild type AIV in mice.
      The HIV/H5-HA virus was able to infect 293T, BHK, Vero, PK-15, MDCK cells but not
      IBRS-2 cells and therefore demonstrated cell tropism similar to the wild type
      AIV. HIV/H5-HA agglutinated chicken erythrocytes and cell entry was blocked by
      ammonium chloride, indicating that the process is pH-dependent. In mice, HIV/H5
      HA immunization resulted in low levels of virus in the lungs, elicited high
      levels of AIV HA-specific antibody as indicated by the hemagglutination
      inhibition (HI) test, and the antibody induction was both earlier and with a
      higher titer than that induced by the inactivated AIV vaccine. These results
      confirmed the roles played by HA in AIV infection and immunogenicity and
      suggested that the pseudotyped lentivirus is a good model for studying the
      functions of AIV HA.

PMID- 18812191
TI  - Heparin-like glycosaminoglycans prevent the infection of measles virus in SLAM
      negative cell lines.
AB  - The wide tissue tropism of the measles virus (MV) suggests that it involves
      ubiquitously expressed molecules. We have constructed a recombinant MV expressing
      the enhanced green fluorescent protein (EGFP) (rMV-EGFP) and demonstrated that
      the rMV-EGFP infected several cell types (HEK-293, HepG2, Hep3B, Huh7, and WRL68
      cells) that do not express the human signalling lymphocyte activation molecule
      (SLAM), which is known as a cellular receptor for morbilliviruses. MV infection
      of HEK-293 and HepG2 cells was not inhibited in an infectivity-inhibition assay
      using an anti-SLAM monoclonal antibody, indicating that MV could infect cells
      without using SLAM. Soluble heparin (HP) inhibited the rMV-EGFP infectivity in
      SLAM-negative cell lines in a dose-dependent manner. Direct interaction between
      purified virions and HP was detected in a surface plasmon resonance assay. We
      also demonstrated that the hemagglutinin (H) protein, but not the fusion (F)
      protein is responsible for the interaction between the virions and HP. Taken
      together, our results suggest that HP-like glycosaminoglycans bind to the H
      protein of MV and play a key role in the infection of SLAM-negative cells.

PMID- 18812192
TI  - Selenocysteine incorporation in Kinetoplastid: selenophosphate synthetase (SELD)
      from Leishmania major and Trypanosoma brucei.
AB  - Selenophosphate synthetase (EC 2.7.9.3), the product of the selD gene, produces
      the biologically active selenium donor compound, monoselenophosphate, from ATP
      and selenide, for the synthesis of selenocysteine. The kinetoplastid Leishmania
      major and Trypanosoma brucei selD genes were cloned and the SELD protein
      overexpressed and purified to apparent homogeneity. The selD gene in L. major and
      T. brucei are respectively 1197 and 1179 bp long encoding proteins of 399 and 393
      amino acids with molecular masses of 42.7 and 43 kDa. The molecular mass of 100
      kDa for both (L. major and T. brucei) SELDs is consistent with dimeric proteins.
      The kinetoplastid selD complement Escherichia coli (WL400) selD deletion
      confirming it is a functional enzyme and the specific activity of these enzymes
      was determined. A conserved Cys residue was identified both by multiple sequence
      alignment as well as by functional complementation and activity assay of the
      mutant (Cys to Ala) forms of the SELD identifying this residue as essential for
      the catalytic function.

PMID- 18812193
TI  - Maximum Likelihood based comparison of the specific growth rates for P.
      aeruginosa and four mutator strains.
AB  - The specific growth rate for P. aeruginosa and four mutator strains mutT, mutY,
      mutM and mutY-mutM is estimated by a suggested Maximum Likelihood, ML, method
      which takes the autocorrelation of the observation into account. For each
      bacteria strain, six wells of optical density, OD, measurements are used for
      parameter estimation. The data is log-transformed such that a linear model can be
      applied. The transformation changes the variance structure, and hence an OD
      dependent variance is implemented in the model. The autocorrelation in the data
      is demonstrated, and a correlation model with an exponentially decaying function
      of the time between observations is suggested. A model with a full covariance
      structure containing OD-dependent variance and an autocorrelation structure is
      compared to a model with variance only and with no variance or correlation
      implemented. It is shown that the model that best describes data is a model
      taking into account the full covariance structure. An inference study is made in
      order to determine whether the growth rate of the five bacteria strains is the
      same. After applying a likelihood-ratio test to models with a full covariance
      structure, it is concluded that the specific growth rate is the same for all
      bacteria strains. This study highlights the importance of carrying out an
      explorative examination of residuals in order to make a correct parametrization
      of a model including the covariance structure. The ML method is shown to be a
      strong tool as it enables estimation of covariance parameters along with the
      other model parameters and it makes way for strong statistical tools for
      inference studies.

PMID- 18812194
TI  - Natural antisense transcripts are co-expressed with sense mRNAs in
      synaptoneurosomes of adult mouse forebrain.
AB  - Natural antisense transcripts and overlapping sense transcripts are expressed in
      a variety of tissues, including adult mouse brain. Here we show that a subset of
      mRNA-like sense-antisense transcript pairs are co-expressed within
      synaptoneurosomes of adult mouse forebrain, a subcellular fraction that is
      enriched in pinched-off dendritic spines of pyramidal neurons. Several of these
      pairs involve mRNAs that have been implicated in synaptic functions and in
      Alzheimer disease pathways. This study provides evidence that a new class of
      noncoding RNAs (natural antisense transcripts) are expressed near synapses, and
      encourages further studies of their roles in neuronal function.

PMID- 18812195
TI  - Oligoethylenimine-grafted polypropylenimine dendrimers as degradable and
      biocompatible synthetic vectors for gene delivery.
AB  - Several grafted polypropylenimine dendrimers were synthesized by modifying either
      polypropylenimine (PPI) dendrimer generation 2 (G2) or generation 3 (G3) via 1.6
      hexandioldiacrylate with branched oligoethylenimine 800Da (OEI) or PPI dendrimer
      G2. The resulting derivatives were characterized ((1)H NMR, GPC) and their
      biophysical properties such as DNA condensing ability, colloidal stability and
      hydrodynamic diameters were determined. All grafted dendrimers were able to
      efficiently compact DNA to nanosized polyplexes (100-200 nm) and exhibited an
      increased colloidal stability as compared to their unmodified counterparts. In
      vitro, grafted dendrimers resulted in much higher transfection levels as compared
      to the unmodified ones displaying alongside a clear structure-activity
      relationship regarding their transfection/toxicity profile. Transfection levels
      of OEI-grafted dendrimers were the highest, being similar or even higher as
      compared to standard polyethylenimines (linear and branched), demonstrating that
      the incorporation of ethylenimine moieties is the key factor contributing to this
      boosted transfection efficiency. None of the compounds resulted in polymer
      induced erythrocyte aggregation. Upon i.v. injection of OEI-grafted dendrimer
      polyplexes into tumor-bearing mice transgene expression was predominantly found
      in the (subcutaneous) tumors. Importantly, the tumor gene expression levels
      significantly increased with the higher dendrimer core generation.

PMID- 18812196
TI  - Inhibitory CD8+ T cells in autoimmune disease.
AB  - Rheumatologists have long been focused on developing novel immunotherapeutic
      agents to manage such prototypic autoimmune diseases as rheumatoid arthritis (RA)
      and systemic lupus erythematosus (SLE). The ultimate challenge in providing
      immunosuppressive treatment for patients with RA and SLE has derived from the
      dilemma that both protective and harmful immune responses result from adaptive
      immune responses, mediated by highly diverse, antigen-specific T and B cells
      endowed with powerful effector functions and the ability for long-lasting memory.
      As regulatory/suppressor T cells can suppress immunity against any antigen,
      including self-antigens, they emerge as an ideal therapeutic target. Several
      distinct subtypes of CD8(+) suppressor cells (Ts) have been described that could
      find application in treating RA or SLE. In a xenograft model of human synovium,
      CD8(+)CD28(-)CD56(+) T cells effectively suppressed rheumatoid inflammation.
      Underlying mechanisms involve conditioning of antigen presenting cells (APC).
      Adoptively transferred CD8(+) T cells characterized by IL-16 secretion have also
      exhibited disease-inhibitory effects. In mice with polyarthritis, CD8(+) Ts
      suppressed inflammation by IFNgamma-mediated modulation of the tryptophan
      metabolism in APC. In SLE animal models, CD8(+) Ts induced by a synthetic peptide
      exerted suppressive activity mainly via the TGFbeta-Foxp3-PD1 pathway. CD8(+) Ts
      induced by histone peptides were found to downregulate disease activity by
      secreting TGFbeta. In essence, disease-specific approaches may be necessary to
      identify CD8(+) Ts optimally suited to treat immune dysfunctions in different
      autoimmune syndromes.

PMID- 18812197
TI  - Human CD8+ T-regulatory cells with low-avidity T-cell receptor specific for minor
      histocompatibility antigens.
AB  - Maternal/fetal microchimerism resulting from cell exchanges during pregnancy
      constitutes a reservoir of persisting alloantigen in mother and adult offspring.
      These alloantigens induce minor histocompatibility antigen-specific immune
      responses in both the mother and her offspring, including CD8(+) T regulatory
      (T(R)) cells with low T-cell receptor binding to major histocompatibility complex
      tetramers. Although they bind cognate major histocompatibility complex/peptide
      relatively poorly, these CD8 T(R) nonetheless inhibit high-avidity, tetramer
      bright CD8 T effector responding to the same minor H antigen through induction of
      immunosuppressive DC products. In this review article we explore the mechanisms
      of such "low-avidity" CD8 T(R)-dependent suppression and discuss their role in
      naturally acquired tolerance to familial minor histocompatibility antigens
      encountered during gestation and in parous women. We discuss the implications of
      our findings for chronic/persisting viral infections, residual tumor burden after
      cancer treatment and immunotherapy, and renal allograft tolerance.

PMID- 18812198
TI  - Influence of maternal antibody against hepatitis B surface antigen on active
      immune response to hepatitis B vaccine in infants.
AB  - Transplacentally acquired maternal antibodies in infants may inhibit active
      immune responses to vaccines. In this study, we compared the immunogenicity of
      the recombinant hepatitis B vaccine, which was intramuscularly injected at 0, 1,
      and 6 months of age, in 71 infants born to mothers with positive or negative
      antibody against hepatitis B surface antigen (anti-HBs). Forty-one infants born
      to anti-HBs positive mothers were all positive at birth. At 2 months after the
      second injection, anti-HBs in 30 infants with negative maternal antibody was
      significantly higher than that in 41 infants with positive maternal anti-HBs
      (191.1mIU/ml vs. 96.2mIU/ml, P=0.018). At one month after the full immunization,
      the anti-HBs levels had no statistical difference between maternal anti-HBs
      negative and positive groups, but the antibody response in infants with high
      maternal anti-HBs (>1000mIU/ml) was significantly inhibited. Nevertheless, all
      infants had anti-HBs higher than the protective level. In conclusion, passively
      acquired maternal anti-HBs in infants may to some extent impair the antibody
      response to hepatitis B vaccine. The long-term efficacy of hepatitis B vaccine in
      infants with high titers of maternal anti-HBs remains to be further evaluated.

PMID- 18812199
TI  - Potent specific immune responses induced by prime-boost-boost strategies based on
      DNA, adenovirus, and Sendai virus vectors expressing gag gene of Chinese HIV-1
      subtype B.
AB  - To study the immune responses elicited by multiple vectors and develop vaccines
      strategies against prevalent HIV-1 strains in China, we have examined the potency
      of vaccine regimens of plasmid DNA, adenovirus, and Sendai virus vectors
      expressing HIV-1 gag consensus sequence of HIV-1 isolates from China for inducing
      specific immune responses. In BALB/c mice, combination of these vectors induced
      higher Gag-specific cellular immune response than any regimen using single vector
      alone. The prime-boost-boost regimen consisting of the triple heterologous
      vectors induced Gag-specific T-cell responses the most efficiently. In rhesus
      macaques, the prime-boost-boost regimen induced potent Gag-specific cellular
      immune responses as well as long lasting humoral immune response, and each
      booster resulted in rapid and efficient expansion of Gag-specific T cells. These
      results indicate that this prime-boost-boost regimen using triple heterologous
      vectors is a promising AIDS vaccine candidate for efficiently inducing HIV-1
      specific cellular and humoral immune responses. Its further studies as a
      promising scheme for therapeutic and/or prophylactic HIV-1 vaccines should be
      grounded.

PMID- 18812200
TI  - Double immunization strategy with a BoHV-4-vectorialized secreted chimeric
      peptide BVDV-E2/BoHV-1-gD.
AB  - A bovine herpesvirus 4 was isolated from the milk cell fraction of a healthy cow
      and his full genome cloned as a bacterial artificial chromosome. So cloned viral
      genome was used as a vector platform to deliver in vitro and in vivo an optimized
      secreted chimeric peptide obtained by the fusion of the bovine viral diarrhoea
      virus glycoprotein E2 ectodomain with the bovine herpesvirus 1 glycoprotein D
      ectodomain. Recombinant virus infected cells robustly expressed and secreted the
      chimeric peptide into the culture medium and inoculated animals with the
      recombinant virus successfully responded toward antigens, gE2 and gD. Thus, this
      work has implications for the development of safe and effective polyvalent
      vaccines.

PMID- 18812201
TI  - Modification of CEA with both CRT and TAT PTD induces potent anti-tumor immune
      responses in RNA-pulsed DC vaccination.
AB  - Carcinoembryonic antigen (CEA) is expressed on human colon carcinomas, is well
      characterized, and continues to be a promising target for cancer immunotherapy in
      humans. To enhance the immunogenecity of CEA, we developed a fusion gene (CRT-TAT
      DeltaCEA) of the TAT protein transduction domain (PTD) and calreticulin (CRT)
      with human CEA devoid of its signal sequences (DeltaCEA) and evaluated anti-tumor
      immunity using RNA-pulsed dendritic cell (DC) vaccination. Mice vaccinated with
      DC by electroporation with mRNA encoding TAT-DeltaCEA (DC/TAT-DeltaCEA) and CRT
      DeltaCEA (DC/CRT-DeltaCEA) had enhanced induction of tumor-specific cytotoxic T
      lymphocyte (CTL) and increased numbers of IFN-gamma-secreting T cells by ELISPOT,
      as compared to mice vaccinated with DC/DeltaCEA. DC/CRT-DeltaCEA and DC/TAT
      DeltaCEA vaccines preferentially stimulated CD4+ and CD8+ T cells, respectively.
      The DC vaccine by electroporation with mRNA encoding CRT-TAT-DeltaCEA (DC/CRT-TAT
      DeltaCEA) enhanced both CD4+ and CD8+ T cells. DC/CRT-TAT-DeltaCEA had the
      additional effects of CRT and TAT PTD and enhanced the anti-tumor effect against
      CEA-expressing tumors compared to DC/CRT-DeltaCEA or DC/TAT-DeltaCEA. These
      findings suggest that modification of CEA with both CRT and TAT PTD induces
      potent anti-tumor immune responses in RNA-pulsed DC vaccination and may be a
      useful approach for DC-based immunotherapy.

PMID- 18812202
TI  - Lessons from IAVI-006, a phase I clinical trial to evaluate the safety and
      immunogenicity of the pTHr.HIVA DNA and MVA.HIVA vaccines in a prime-boost
      strategy to induce HIV-1 specific T-cell responses in healthy volunteers.
AB  - IAVI-006 was the first large randomised, double-blinded, placebo-controlled Phase
      I clinical trial to systematically investigate the prime-boost strategy for
      induction of HIV-1 specific CD8+ cytotoxic T-lymphocytes (CTL) in a factorial
      trial design using (i) priming with 0.5 mg or 2 mg of pTHr.HIVA DNA vaccine,
      followed by (ii) two booster vaccinations with 5 x 10(7) MVA.HIVA at weeks 8 and
      12 (early boost) or weeks 20 and 24 (late boost). This study set the basis for
      later clinical trials and demonstrated the safety of these candidate HIV
      vaccines. The safety and immunogenicity results are presented and the lessons
      derived from this clinical trial are discussed.

PMID- 18812203
TI  - DNA vaccine protects ornamental koi (Cyprinus carpio koi) against North American
      spring viremia of carp virus.
AB  - The emergence of spring viremia of carp virus (SVCV) in the United States
      constitutes a potentially serious alien pathogen threat to susceptible fish
      stocks in North America. A DNA vaccine with an SVCV glycoprotein (G) gene from a
      North American isolate was constructed. In order to test the vaccine a challenge
      model utilizing a specific pathogen-free domestic koi stock and a cold water
      stress treatment was also developed. We have conducted four trial studies
      demonstrating that the pSGnc DNA vaccine provided protection in vaccinated fish
      against challenge at low, moderate, and high virus doses of the homologous virus.
      The protection was significant (p < 0.05) as compared to fish receiving a mock
      vaccine construct containing a luciferase reporter gene and to non-vaccinated
      controls in fish ranging in age from 3 to 14 months. In all trials, the SVCV-G
      DNA immunized fish were challenged 28-days post-vaccination (546 degree-days) and
      experienced low mortalities varying from 10 to 50% with relative percent
      survivals ranging from 50 to 88%. The non-vaccinated controls and mock construct
      vaccinated fish encountered high cumulative percent mortalities ranging from 70
      to 100%. This is the first report of a SVCV DNA vaccine being tested successfully
      in koi. These experiments prove that the SVCV DNA (pSGnc) vaccine can elicit
      specific reproducible protection and validates its potential use as a
      prophylactic vaccine in koi and other vulnerable North American fish stocks.

PMID- 18812204
TI  - SCN8A as a novel candidate gene associated with bipolar disorder in the Han
      Chinese population.
AB  - BACKGROUND: Bipolar disorder (BPD) is a common, severe and recurrent psychiatric
      disorder. It has been suggested that BPD patients have a higher risk of suicide
      than patients with any other psychiatric illnesses. A recent study found that
      suicide attempt was associated with the SCN8A gene, which has been mapped close
      to one of the BPD susceptibility loci. Thus, SCN8A is likely to be a candidate
      gene for BPD. METHODS: In this study, three SNPs (rs1601012, rs303810, rs60637)
      were analyzed in 506 bipolar patients and 507 controls of Han origin. RESULTS: We
      found that two individual SNPs showed statistically significant differences
      between cases and controls in both allele and genotype distribution, but only
      rs303810 was still significant in allele distribution (p=0.0164) after
      correction. No obvious linkage disequilibrium or haplotypes were observed among
      these SNPs. CONCLUSION: Our results indicate that SCN8A may be a potential
      susceptibility gene for bipolar disorder in the Han Chinese population.

PMID- 18812205
TI  - Lamotrigine in the treatment of comorbid bipolar spectrum and bulimic disorders:
      case series.

PMID- 18812206
TI  - An integrated psychobiological predictive model of emergent psychopathology among
      young relatives at risk for schizophrenia.
AB  - OBJECTIVE: Studies of young relatives at elevated risk for schizophrenia have
      pointed to the importance of a variety of neurobiological, cognitive, and
      clinical risk factors for the disorder; yet few have employed integrated models
      to estimate the joint contribution of these factors to heightened schizophrenic
      risk. We tested the predictive power of an integrated psychobiological model of
      schizophrenia risk to subsequent psychopathology development among young
      relatives at risk for the disorder. METHODS: Young first (n=66) and second (n=20)
      degree relatives of schizophrenia probands were followed for an average of 3
      (SD=1.13) years to examine their trajectories toward psychopathology development.
      Neurobiologic, cognitive, and clinical measures were employed in an integrated
      structural equation model to estimate their contribution to the prospective
      emergence of psychopathology. RESULTS: Results indicated that neurobiological,
      neurocognitive, and psychosis proneness factors at baseline were all uniquely
      predictive of subsequent psychopathology development, and that an integrated
      model of psychopathology development that took into account these factors
      provided an excellent fit to the observed data. Subsequent classification
      analyses of model accuracy using likelihood ratios adjusting for the base-rate of
      psychopathology development in this sample revealed that individuals identified
      by this model had a 71% chance of developing psychopathology in the future.
      CONCLUSIONS: An integrated model of biobehavioral risk factors may provide a
      powerful method for predicting psychopathology and schizophrenia risk in at-risk
      samples. If validated, this model may be useful for early detection and
      intervention programs. Future research will need to focus particularly on
      predicting schizophrenia development and refining models to further enhance
      sensitivity.

PMID- 18812207
TI  - Potential in vitro antioxidant and protective effects of Soymida febrifuga on
      ethanol induced oxidative damage in HepG2 cells.
AB  - There is increasing evidence that oxidative stress is implicated in pathogenesis
      of various diseases, including alcoholic liver injury. In the present study, we
      investigated the comparative protective effects of leaf, bark, root and root bark
      extracts of Soymida febrifuga (Roxb.) A. Juss. (Meliaceae) against ethanol
      induced oxidative damage in HepG2 cells. Comparatively, methanolic and aqueous
      extracts of bark and leaf significantly attenuated the cytotoxicity of the
      ethanol, as determined by cytotoxicity, lipid peroxidation, lactate
      dehydrogenase, alanine aminotransferases and asparatate aminotransferases, than
      the root and root bark extracts. Ethanol induces liver toxicity through free
      radical generation so initially in vitro antioxidant activity of the extracts was
      evaluated. Methanolic and aqueous extracts of bark and leaf have shown higher
      total phenolic content, reducing power, metal chelating, superoxide, hydroxyl
      radical, hydrogen peroxide and nitric oxide (murine macrophage cells) scavenging
      activity than the root and root bark extracts.

PMID- 18812208
TI  - Relative involvement of three 17beta-hydroxysteroid dehydrogenases (types 1, 7
      and 12) in the formation of estradiol in various breast cancer cell lines using
      selective inhibitors.
AB  - We investigated the relative involvement of three reductive 17beta-hydroxysteroid
      dehydrogenase (17beta-HSD) isoforms, namely types 1, 7 and 12, in the formation
      of potent estrogen estradiol (E2) in 10 human breast cancer cell lines (T-47D,
      MCF-7, ZR-75-1, CAMA-1, BT-20, BRC-17, BRC-31, BRC-32, BRC-36 and BRN-196) and
      also in 1 choriocarcinoma cell line (JEG-3) using selective inhibitors. In T-47D,
      BT-20 and JEG-3 cells, a 17beta-HSD1 inhibitor almost completely inhibited the
      formation of E2 at 1microM from 60nM of estrone (E1) (98%, 91% and 90%,
      respectively), whereas no significant inhibition of E2 formation was obtained
      using inhibitors of types 7 and 12. However, we obtained lower levels of
      inhibition (32%, 36% and 35% respectively using inhibitors of types 1, 7 and 12
      at 10microM) in MCF-7 cells and even lower and variable levels of inhibition
      (15%, 23% and 18% respectively using inhibitors of types 1, 7 and 12 at 10microM)
      in ZR-75-1 cells. No inhibition of E2 formation was observed in CAMA-1 cells with
      a 17beta-HSD1 inhibitor at 1microM whereas inhibitors of types 7 and 12 inhibited
      40% and 30% of E2 formation, respectively. In BRC and BRN cell lines, types 1, 7
      and 12 17beta-HSDs were all involved in the formation of E2, but type 12 seemed
      to predominate. At 10microM, each inhibitor inhibited 10-50% of the formation of
      E2. Using MCF-7 and BRC-32 cell lines, a combination of the three inhibitors
      (3x10microM) does not fully inhibit the 17beta-HSD activity (65% and 75%). In
      addition to identify the relative importance of types 1, 7 and 12 17beta-HSDs in
      the formation of E2 in human breast cancer cell lines, our results show also a
      great variability between each cell line. In some cases the formation of E2 was
      completely inhibited, but this was not the result observed in other cell lines,
      suggesting the presence of another enzyme involved in the biosynthesis of E2.

PMID- 18812209
TI  - Angiotensin II regulation of adrenocortical gene transcription.
AB  - Angiotensin II (Ang II) is the key peptide hormone in the renin-angiotensin
      aldosterone system (RAAS). Its ability to regulate levels of circulating
      aldosterone relies on actions on adrenal glomerulosa cells. Many of the Ang II
      effects on glomerulosa cells involve a precisely coordinated regulation of
      signaling cascades and gene expression. The development of genome-wide gene
      arrays has allowed the definition of transcriptome-wide effects of Ang II in
      adrenocortical cells. Analysis of the Ang II gene targets reveals broad effects
      on cellular gene expression, particularly the rapid induction of numerous
      transcription factors that may regulate long-term steroid metabolism and cell
      growth/proliferation. Herein we discuss the Ang II-induced genes in
      adrenocortical cells and review the progress in defining the role of these genes
      in zona glomerulosa function.

PMID- 18812210
TI  - Attenuation of ethanol-induced ataxia by alpha(4)beta(2) nicotinic acetylcholine
      receptor subtype in mouse cerebellum: a functional interaction.
AB  - Many epidemiological studies support the notion that people who drink alcohol
      also smoke cigarettes and vice versa thereby suggesting a possible functional
      interaction between these two most widely used psychoactive substances. We have
      earlier demonstrated that direct intracerebellar (ICB) microinfusion of nicotine
      dose-dependently antagonizes ethanol-induced ataxia and further that this
      antagonism occurs in a glutamate-nitric oxide-cyclic guanylyl monophosphate
      (cGMP) sensitive manner. The present study was designed to determine the possible
      involvement of specific nicotinic acetylcholine receptor (nAChR) subtype
      alpha(4)beta(2) in nicotine-induced attenuation of ethanol ataxia. Using the
      Rotorod test and direct ICB microinfusion technique in stereotaxically cannulated
      CD-1 male mice, we performed the Rotorod test following ICB administration of the
      alpha(4)beta(2)-selective agonist, (E)-N-methyl-4-(3-pyridinyl)-3-buten-1-amine
      (RJR-2403; 31.25, 62.5, 125 ng) on ethanol (2 g/kg; i.p.) ataxia at 15, 30, 45,
      60 min post-ethanol injection. RJR-2403 dose-dependently attenuated ethanol
      ataxia suggesting a role of alpha(4)beta(2) subtype in ameliorating ethanol
      induced ataxia. Pretreatment with ICB dihydro-beta-erythroidine (DHbetaE: 125,
      250, 500, 750 ng), a potent alpha(4)beta(2)-selective antagonist, significantly
      reduced RJR-2403's effect further supporting the alpha(4)beta(2) involvement.
      DHbetaE (ICB) also antagonized ICB nicotine-induced attenuation of ethanol ataxia
      again reinforcing the role of alpha(4)beta(2) subtype. Additional evidence for
      the role of alpha(4)beta(2) subtype was provided when ICB alpha(4)beta(2)
      antisense oligodeoxynucleotide treatment markedly antagonized RJR 2403-induced
      attenuation of ethanol ataxia compared with missense-treated animals. This was
      confirmed with an associated decrease in the expression of alpha(4)beta(2)
      subtypes indicated by immunoblot experiments. In conclusion, the results of the
      present investigation support an important role of alpha(4)beta(2) nAChR subtype
      in the expression of nicotine-induced attenuation of ethanol ataxia.

PMID- 18812211
TI  - Transcriptional profiles reveal similarities and differences in the effects of
      developmental neurotoxicants on differentiation into neurotransmitter phenotypes
      in PC12 cells.
AB  - Unrelated developmental neurotoxicants nevertheless converge on common functional
      and behavioral outcomes. We used PC12 cells, a model of neuronal development, to
      explore similarities and differences for organophosphate pesticides
      (chlorpyrifos, diazinon), an organochlorine pesticide (dieldrin) and a metal
      (Ni(2+)), focusing on transcriptional profiles related to differentiation into
      acetylcholine, dopamine and norepinephrine phenotypes. Agents were introduced at
      30 microM for 24 or 72 h, treatments devoid of cytotoxicity. Using microarrays,
      we examined the mRNAs encoding the proteins involved in neurotransmitter
      biosynthesis, storage, and degradation, along with the complete panoply of
      receptors for each transmitter. All three pesticides evoked concordant patterns
      of effects on genes involved in neural growth and neurite extension, with a
      distinctly different pattern for Ni(2+). All four toxicants promoted
      differentiation into the dopamine phenotype at the expense of the acetylcholine
      phenotype, involving separable effects of each agent on the various gene
      families; however, there were major differences in the ability of each to promote
      or repress the norepinephrine phenotype. Chlorpyrifos and diazinon, although
      displaying many similarities in their transcriptional profiles, also showed major
      disparities in keeping with their known differences in synaptic and behavioral
      outcomes after neonatal exposures to these agents in vivo. Surprisingly, there
      were closer similarities among diazinon, dieldrin and Ni(2+) than for each agent
      to chlorpyrifos. Our results illustrate how cell culture systems, combined with
      microarray technology, can screen for developmental neurotoxicants, serving as a
      model for alternative approaches to the detection and characterization of the
      impact of exogenous chemicals on brain development.

PMID- 18812212
TI  - Targeting the caudal intralaminar nuclei for functional neurosurgery of movement
      disorders.
AB  - The caudal intralaminar nuclei, in particular the Centrum-Medianum
      Parafascicularis (CM-Pf) nucleus complex, are involved in various functions,
      particularly in pain processing and in motor control, through their projections
      to the subthalamic nucleus and their afferents from the pallidum internus (GPi)
      (or entopeduncular nucleus in the rat). The nociceptive inputs received by the CM
      Pf are modulated by the somato-sensory thalamus. The lateral habenula (HbL)
      receives noxious inputs and has an inhibitory influence on the nigral
      dopaminergic neurons. CM-Pf and the HbL share comparable response characteristics
      to noxious inputs and might play comparable, and perhaps complementary, roles in
      conveying the nociceptive information to the basal ganglia system, thereby
      modulating motor responses, such as freezing and dyskinesias. The interaction
      between CM-Pf, HbL, GPi, STN and SNC might provide a new template for high
      frequency stimulation strategies in the treatment of movement disorders.

PMID- 18812213
TI  - Magnesium treatment and spontaneous mild hypothermia after transient focal
      cerebral ischemia in the rat.
AB  - There is evidence from global cerebral ischemia experiments in the rat that the
      neuroprotection attributable to magnesium treatment depends on the concurrent
      presence of at least mild hypothermia. We set out to determine to what extent
      spontaneous hypothermia occurred after transient middle cerebral artery occlusion
      in the rat, and whether this hypothermia influenced the outcome of magnesium
      treatment. We found that rectal temperatures from 30 min to 3h after recovery
      from anaesthesia/surgery were 1  degrees C lower than in the period from 4 to 6h.
      Striatal infarcts were significantly reduced by 32% in animals treated with 360
      MUmol/kg MgSO(4) intravenously immediately prior to ischemia. A higher magnesium
      dose of 720 MUmol/kg had not effect on infarct volume. Having previously
      established that these two doses of magnesium are ineffective in normothermic
      animals using this model, we conclude that the mild spontaneous hypothermia
      contributed to the observed neuroprotective effect of magnesium in this study,
      and that previous studies of magnesium in cerebral ischemia have likely been
      confounded in this way.

PMID- 18812214
TI  - Multi-target strategy for Parkinsonian patients: the role of deep brain
      stimulation in the centromedian-parafascicularis complex.
AB  - The intra-laminar (IL) thalamic complex, composed of centromedian (CM) and
      parafascicular (Pf) nucleus, is a strategic crossroad for the activity of the
      basal ganglia and is recently regaining its position has a putative neurosurgical
      target for Parkinsonian syndromes. The multi-target approach we have encouraged
      since the late nineties has allowed the combined implantation of a standard
      target (the subthalamic nucleus-STN or the internal pallidus-GPi) plus an
      innovative one (CM/Pf) in well-identified Parkinson's disease (PD) patients;
      hence, it is possible to study, in the same PD patients, the specific target
      mediated effects on different clinical signs. Here, we focus on the potential
      usefulness of implanting the CM/Pf complex when required in the management of
      contra-lateral tremor (resistant to standard deep brain stimulation-DBS - in STN 
      , n=2) and disabling involuntary movements, partially responsive to GPi-DBS
      (n=6). When considering global UPDRS scores, CM/Pf-DBS ameliorate extra-pyramidal
      symptoms but not as strongly as STN (or GPi) does. Yet, CM/Pf acts very
      powerfully on tremor and contributes to the long-term management of l-Dopa
      induced involuntary movements. The lack of cognitive deficits and psychic
      impairment associated with the improvement of their quality of life, in our small
      cohort of CM/Pf implanted patients, reinforces the notion of CM/Pf as a safe and
      attractive area for surgical treatment of advanced PD, possibly affecting not
      only motor but also associative functions.

PMID- 18812215
TI  - Evaluation of ethyl acetate on three dimensions: investigation of behavioral,
      physiological and psychological indicators of adverse chemosensory effects.
AB  - A variety of national occupational exposure limits for ethyl acetate exist based
      on different studies, mostly relying on subjective evaluations of ethyl acetate
      as an irritant. Only one study also used physiological methods with inconsistent
      results in subjective and objective data. The present study was designed to
      investigate ethyl acetate on three different dimensions: behavioral,
      physiological and psychological indicators of adverse chemosensory effects were
      investigated during acute exposures to different concentrations of ethyl acetate.
      Twenty-four subjects were challenged with ethyl acetate in three exposure
      patterns (2 ppm, 400 ppm, 400 ppm including peaks of 800 ppm). While the odor
      intensity is rated "strong", trigeminal perceptions were rated less than
      "moderate". The absence of substantial trigeminal ratings was supported by
      physiological data. There was neither an effect of concentration on blinking
      frequency nor on nasal resistance which both are indicators of irritation.
      Furthermore, there are no effects of ethyl acetate concentration on behavioral
      measures indicating no olfactory or trigeminally mediated disturbance of
      cognitive processing. In conclusion, the results of this multilevel approach
      revealed no adverse chemosensory effects at ethyl acetate concentrations as
      recommended by the German MAK-value.

PMID- 18812216
TI  - The toxicology of Clioquinol.
AB  - 5-Chloro-7-iodo-quinolin-8-ol (Clioquinol) is a halogenated 8-hydroxyquinoline
      that was used in 1950-1970s as an oral anti-parasitic agent for the treatment and
      prevention of intestinal amebiasis. However in the 1970s oral Clioquinol was
      withdrawn from the market due to reports of neurotoxicity in Japanese patients.
      Recently, reports have demonstrated that Clioquinol has activities beyond its use
      as an antimicrobial. For example, Clioquinol inhibits the function of the
      proteasome and displays preclinical efficacy in the treatment of malignancy. In
      addition, due to its ability to bind copper and dissolve beta-amyloid plaques in
      the brain, Clioquinol has been investigated for the treatment of Alzheimer's
      disease. As such, efforts are underway to repurpose Clioquinol. In light of the
      reemergence of oral Clioquinol, we review the toxicology of this compound in
      animals and humans with an emphasis on its neurotoxicity. Such information will
      aid in the design of clinical trials of oral Clioquinol for new indications such
      as cancer therapy.

PMID- 18812217
TI  - Poly(I:C) coated PLGA microparticles induce dendritic cell maturation.
AB  - Microparticles from poly(D,L-lactic-co-glycolic acid) [PLGA] are of steadily
      rising interest for the delivery of antigens to immune cells and the induction of
      a long-lasting immune response for vaccination or immunological tumor therapy.
      However, if the desired vaccine contains only weak antigens and fails to activate
      the antigen presenting cells (APC), the opposite effect, i.e., the induction of
      immunotolerance may be observed. Therefore, it was the aim of this study to show
      the ability of protein loaded PLGA microparticles to additionally carry a
      specific, surface-coated maturation signal to human dendritic cells (DC), i.e.,
      the most potent APC. Polyinosine-polycytidylic acid [poly(I:C)], a ligand of Toll
      like receptor (TLR) 3, was efficiently bound either in a single layer or a
      multilayer attempt to the surface of diethylaminoethyl dextran modified PLGA
      microparticles. These particles were effectively phagocytized by DC ex vivo and
      induced a maturation similar to that achieved with a cytokine cocktail or higher
      concentrations of soluble poly(I:C). In conclusion, the concept of surface
      coating of biodegradable microparticles with selected TLR ligands might
      successfully be used in DC-based cell therapies for cancer or in vaccination
      trials to induce DC maturation and specifically amplify the immunological
      response to encapsulated antigens.

PMID- 18812218
TI  - Microneedle mediated delivery of nanoparticles into human skin.
AB  - The development of novel cutaneous delivery technologies that can produce micron
      sized channels within the outermost skin layers has stimulated interest in the
      skin as an interface for localised and systemic delivery of macromolecular and
      nanoparticulate therapeutics. This investigation assesses the contribution of
      physicochemical factors to the rate and extent of nanoparticle delivery through
      microchannels created in a biological tissue, the skin, by novel delivery
      technologies such as the microneedle array. The hydrodynamic diameter, zeta
      potential and surface morphology of a representative fluorescent nanoparticle
      formulation were characterised. Permeation studies using static Franz-type
      diffusion cells assessed (i) the diffusion of nanoparticle formulations through a
      model membrane containing uniform cylindrical microchannels of variable diameter
      and (ii) nanoparticle penetration across microneedle treated human skin. Wet-etch
      microneedle array devices can be used to significantly enhance the
      intra/transdermal delivery of nanoparticle formulations. However the
      physicochemical factors, microchannel size and particle surface charge, have a
      significant influence on the permeation and subsequent distribution of a
      nanoparticle formulation within the skin. Further work is required to understand
      the behaviour of nanoparticle formulations within the biological environment and
      their interaction with the skin layers following disruption of the skin barrier
      with novel delivery devices such as the microneedle array.

PMID- 18812219
TI  - Comparison of noise-induced changes of auditory brainstem and middle latency
      response amplitudes in rats.
AB  - Auditory brainstem responses (ABRs) and middle latency responses (MLRs) were
      compared after noise exposure to elucidate the specific effects of a loud sound
      on the central auditory system in rats. Rats were exposed twice for 1 h to broad
      band noise (BBN) of 118 dB SPL (first exposure) and 122 dB SPL (second exposure)
      with an interval between the exposures of three weeks. The first noise exposure
      produced threshold shifts (TSs) amounting to 5-45 dB, and the second exposure
      resulted in 40-70 dB TSs. The slope of MLR amplitude-intensity functions (AIFs)
      increased significantly in correlation with the TS, resembling loudness
      recruitment. However, maximal MLR amplitudes measured at 8 kHz increased after
      the first and second noise exposures to almost equal values in individual animals
      regardless of the TS. In addition, maximum MLR amplitude enhancement was
      dependent on pre-exposure MLR voltage, probably reflecting the level of metabolic
      activity or neurotransmitter processes in individual animals. In contrast to MLR
      amplitudes, ABR amplitudes were suppressed after noise exposure without changing
      the slope of ABR AIFs. The MLR changes reflect the specific effects of noise
      exposure on the central auditory system.

PMID- 18812220
TI  - Application of frequency modulated chirp stimuli for rapid and sensitive ABR
      measurements in the rat.
AB  - Rodents have proven to be a useful model system to screen genes, ototoxic
      compounds and sound exposure protocols that may play a role in hearing loss. High
      throughput screening depends upon a rapid and reliable functional assay for
      hearing loss. This study describes the use of a frequency modulated (FM) chirp
      stimulus as an alternative to the click to derive a rapid assessment of auditory
      brainstem response (ABR) threshold in the rodent. We designed a rising frequency
      A-chirp based upon the spatial mapping of preferred frequency along the rat
      basilar membrane to provide a more synchronous and equipotent input across the
      length of the cochlea. We observed that the ABR wave I and wave IV amplitudes
      evoked by the A-chirp were significantly greater than the click and that A-chirp
      minimum response thresholds were lower than the click. Subsequent analyses
      compared the efficacy of the A-chirp to linear, time-reversed and amplitude
      reversed chirps and confirmed that the A-chirp was most effective chirp
      configuration. These data suggest that the A-chirp may be optimally suited as a
      single screening broad-frequency stimulus for rapid ABR threshold estimations in
      the rodent and could serve to complement more detailed frequency-specific
      physiologic and behavioral estimates of hearing threshold.

PMID- 18812221
TI  - Influence of various fatty acids on the activity of protein phosphatase type 2C
      and apoptosis of endothelial cells and macrophages.
AB  - In previous work we have demonstrated that protein phosphatase type 2C (PP2C)
      alpha and beta can be activated by mono-unsaturated fatty acids (MUFAs) leading
      to apoptosis of cultured endothelial cells. In the present paper we could show
      that saturated fatty acids (SFAs) did not activate PP2C and did not cause
      apoptosis both in endothelial cells and macrophages. However, long-chain SFAs
      (>16 C-atoms) were capable of inhibiting both, activation of PP2C as well as
      apoptosis of human umbilical vein endothelial cells (HUVECs) and macrophages
      caused by oleic acid. Interestingly, docosahexaenoic acid (DHA) known to protect
      arterial vessels against the progression of atherosclerosis caused apoptosis of
      HUVECs at high concentrations (200-400microM) but inhibited the apoptotic damage
      of HUVECs at a low, physiologically relevant concentration range (1-10microM). In
      contrast, oleic acid did not protect HUVECs against damage even at low
      concentrations (1-25microM). It is supposed that an unbalanced and chronically
      increased level of MUFAs in blood has an atherosclerotic potential. Furthermore,
      PP2C activated by MUFAs appears as a new target for drugs to prevent or treat
      atherosclerosis.

PMID- 18812222
TI  - BNP directly immunoregulates the innate immune system of cardiac transplant
      recipients in vitro.
AB  - BACKGROUND: The innate immune system plays an important role in cardiac allograft
      rejection. BNP has frequently been reported to elevate during acute cardiac
      rejection, yet the explanation behind this phenomenon is unclear. We hypothesized
      that BNP might interact with the innate immune system in cardiac transplant
      recipients and devised a series of in vitro culture experiments to explore this
      phenomena. METHODS: PBMCs were isolated from whole blood of (total n = 40)
      cardiac transplant recipients. Short (24h, n = 20) and long term (72h, n = 20) co
      cultures of innate cells in the presence or absence of BNP were performed. BNP
      was added at two specific concentrations and compared to placebo control. Innate
      cells were immunophenotyped using flow cytometry. RESULTS: BNP dose dependently
      reduced the total number of monocytes, B cells and NK cells. Furthermore, BNP co
      culture impaired NK cell cytotoxicity and adhesion of non-classical monocytes
      (via down-regulation of CD11c). DISCUSSION: BNP has an additional physiological
      role of moderating components of the innate immune system. Although speculative,
      this could be beneficial to cardiac transplant recipients as the innate immune
      system is involved in allograft rejection. Further investigation is required to
      elucidate the mechanism behind how BNP affects immune cells and whether the same
      effects are consistent with the adaptive immune system.

PMID- 18812223
TI  - Pro-survival effects of repetitive low-grade oxidative stress are inhibited by
      simultaneous exposure to Resveratrol.
AB  - V79 lung fibroblasts were subjected to repetitive oxidative stress in culture
      through exposures to 30 microM H(2)O(2) for 4 weeks. Repetitively stressed cells
      were found to be significantly resistant to apoptosis-inducing agent such as
      ultraviolet radiation (UVR). Concurrent treatment with Resveratrol completely
      restored the normal apoptotic response after UVR. p38MAPK became dually
      phosphorylated during the stress period. Akt also became phosphorylated on
      Ser(473) in cells subjected to repetitive oxidative stress. In these cells,
      NFkappaB p65 became phosphorylated and appreciable nuclear localization of p65
      was observed. NFkappaB transcriptional activity also became augmented during
      repetitive stress. Treatment of the repetitively stressed cells concurrently with
      Resveratrol or SB203580, a p38MAPK inhibitor, robustly blocked activation of
      p38MAPK, NFkappaB transcriptional activity, phosphorylation and nuclear
      localization of p65, and Akt phosphorylation. Pre-exposure to short interfering
      RNA (si RNA) to p38MAPK, resulted in a blockage of the Akt and NFkappaB p65
      phosphorylation. However, inhibition of Akt activity through PI3 kinase inhibitor
      LY294002 did not result in obstruction of p38MAPK phosphorylation by H(2)O(2).
      Also, Resveratrol was effective as an antioxidant in counteracting a rise in
      reactive oxygen species (ROS) and p38MAPK activation by H(2)O(2) was completely
      blocked by antioxidant N-acetyl cysteine (NAC). We conclude that Resveratrol acts
      as an antioxidant and completely reverses the anti-apoptotic effects of
      repetitive stress by blocking oxidative stress-induced p38MAPK activation which
      is the key regulatory step for the activation of down-stream survival elements
      Akt and NFkappaB.

PMID- 18812224
TI  - The application and relevance of ex vivo culture systems for assessment of IBD
      treatment in murine models of colitis.
AB  - The aim of this study was to investigate the relevance of mouse ex vivo cultures
      as a first screening model for new therapeutic agents of Inflammatory Bowel
      Disease (IBD). Two murine models (dextran sodium sulphate (DSS)-induced colitis
      and Galphai2-deficient mice) and two anti-inflammatory agents (methyl
      prednisolone and the proteasome inhibitor MG132) were evaluated. The in vivo
      effects of methyl-prednisolone were assessed in both models. Ex vivo colonic
      tissue from both mouse models were cultured in the presence or absence of the
      drugs and TaqMan Low-Density arrays were used to assess the regulation of
      inflammatory genes before and after drug treatment. Colitis induced a similar
      inflammatory gene profile in both mouse models in in vivo studies and in ex vivo
      cultures. The differences encountered reflected the different phases of colitis
      in the models, e.g. innate cytokine/chemokine profile in the DSS model and T cell
      related markers in Galphai2-deficient mice. After steroid treatment, a similar
      pattern of genes was suppressed in the two mouse models. We confirmed the
      suppression of inflammatory gene expression for IL-1beta, IL-6 and iNOS in ex
      vivo and in vivo colons from both mouse models by quantitative RT-PCR.
      Importantly, the inflammatory responses in the murine ex vivo culture system
      reflected the in vivo response in the inflamed colonic tissue as assessed by
      changes in inflammatory gene expression, suggesting that the murine culture
      system can be used for validation of future IBD therapies.

PMID- 18812225
TI  - Recombinant human serine racemase: enzymologic characterization and comparison
      with its mouse ortholog.
AB  - D-serine plays a key role in glutamatergic neurotransmission in mammalian brain
      as a co-agonist of N-methyl-D-aspartate receptors. The enzyme responsible for D
      serine biosynthesis, serine racemase (SR), is therefore a promising target for
      treatment of neuropathologies related to glutamate receptor excitotoxicity, such
      as stroke or Alzheimer's disease. Much of the experimental work to date has been
      performed on mouse serine racemase, which shares a high level of sequence
      identity with its human ortholog. In this work, we report the synthesis of a
      human SR gene variant optimized for heterologous expression in Escherichia coli
      and describe the expression and purification of active recombinant human SR. This
      strategy may be of general interest to researchers wishing to express mammalian
      proteins in a bacterial system. Furthermore, we conduct a thorough analysis of
      the kinetics and inhibitor-sensitivity of the recombinant enzyme, and we provide
      the first direct comparison of human and mouse SR based on our kinetic data. The
      orthologs behave similarly overall and exhibit identical inhibition profiles,
      validating the use of mouse models in SR research.

PMID- 18812226
TI  - Competition between two memory traces for long-term recognition memory.
AB  - Previous studies investigating the processes which underlie memory consolidation
      focused almost exclusively on isolated learning events. Here I studied the
      competition of two similar memory traces for consolidation non-conditioned
      recognition memory in adult male C57BL/6JOlaHsd mice using the olfactory cues
      based social discrimination procedure. My results show that the interference
      phenomena that cause forgetting are time-dependent, and that retroactive
      interference can be discriminated from proactive interference. Furthermore, both
      types of interference can be suppressed by subcutaneous anisomycin treatment
      immediately after presentation of the interference stimulus. These findings imply
      that interference phenomena, which result from the competition of two similar
      memory traces for long-term recognition memory, are related to the progress of
      memory consolidation and linked to protein synthesis.

PMID- 18812227
TI  - Actin polymerization in lateral amygdala is essential for fear memory formation.
AB  - Actin polymerization is involved in key neuronal functions such as intracellular
      trafficking and morphogenesis. In this study, we examined the role of actin
      polymerization in lateral amygdala (LA) in fear conditioning memory formation.
      Microinfusion of cytochalasin D, an actin polymerization inhibitor, into rat LA
      immediately before fear conditioning training impaired the formation of long-term
      fear memory (LTM) but not short-term fear memory (STM). Microinfusion of
      cytochalasin D into rat LA immediately after fear conditioning impaired LTM.
      Cytochalasin D had no effect on fear conditioning memory retrieval when injected
      immediately before LTM test. These results show that actin cytoskeleton
      rearrangement is essential for fear memory consolidation.

PMID- 18812228
TI  - Novel apocarotenoid intermediates in Neurospora crassa mutants imply a new
      biosynthetic reaction sequence leading to neurosporaxanthin formation.
AB  - Neurosporaxanthin, beta-apo-4'-carotenoic acid (C35), represents the end-product
      of the carotenoid pathway in Neurospora crassa. It is supposed to be synthesized
      in three steps catalyzed by sequential AL-2, CAO-2 and YLO-1 activities: (i)
      cyclization of 3,4-didehydrolycopene (C40); (ii) cleavage of torulene into beta
      apo-4'-carotenal (C35); and finally (iii) oxidation of beta-apo-4'-carotenal.
      However, analyses of the ylo-1 mutant revealed the accumulation of intermediates
      other than beta-apo-4'-carotenal. Here, we generated a 3,4-didehydrolycopene
      accumulating Escherichia coli strain and showed that CAO-2 cleaves this acyclic
      carotene in vivo and in vitro yielding apo-4'-lycopenal. The apocarotenoids
      accumulated in the ylo-1 mutant were then identified as apo-4'-lycopenal and apo
      4'-lycopenol, pointing to the former as the YLO-1 substrate and indicating that
      cyclization is the last step in neurosporaxanthin biosynthesis. This was further
      substantiated by analyses of a cyclase-deficient al-2 mutant, revealing the
      accumulation of apo-4'-lycopenoic acid. The three acyclic apocarotenoids
      presented here have not been found naturally before.

PMID- 18812229
TI  - Effects of resveratrol pretreatment on tert-butylhydroperoxide induced hepatocyte
      toxicity in immobilized perifused hepatocytes: involvement of inducible nitric
      oxide synthase and hemoxygenase-1.
AB  - The aim of this work was to study the effects of resveratrol (RES) as compared to
      silymarin (SM) pretreatments on tert-butylhydroperoxide (tBH) induced
      apoptotic/necrotic markers in hepatocytes. Hepatocyte in cultures (48 h) and in
      perifused immobilized agarose threads (5h) were used as cellular systems.
      Hepatocyte apoptosis was estimated morphologically using Annexin-V combined with
      propidium iodide, or toluidine blue staining. Hepatocyte viability and
      functionality were evaluated by ALT and urea synthesis. Nitric oxide (NO) and
      carbon monoxide involvements were also examined. Resveratrol and silymarin
      reduced tBH-induced hepatocyte toxic effects in short term experiments (5h) as
      measured by a significant reduction in ALT and NO increase produced by tBH. Both
      inducible nitric oxide synthase (NOS-2) and hemoxygenase-1 (HO-1) gene expression
      were increased by tBH and reduced by both RES and SM pretreatments.
      Morphologically, there were ameliorations in both apoptotic and necrotic markers
      under RES treatment and were similar to biochemical findings. In addition, RES
      improved hepatocyte stability in both cellular systems. It may be concluded that
      resveratrol and sylimarin ameliorative effects on tBH hepatocyte toxicity are
      comparable; involve NOS-2 and HO-1 expression and should be re-evaluated in
      various in vitro and in vivo experimental conditions.

PMID- 18812230
TI  - Overproduction of free fatty acids in E. coli: implications for biodiesel
      production.
AB  - Whereas microbial fermentation processes for producing ethanol and related
      alcohol biofuels are well established, biodiesel (methyl esters of fatty acids)
      is exclusively derived from plant oils. Slow cycle times for engineering oilseed
      metabolism and the excessive accumulation of glycerol as a byproduct are two
      major drawbacks of deriving biodiesel from plants. Although most bacteria produce
      fatty acids as cell envelope precursors, the biosynthesis of fatty acids is
      tightly regulated at multiple levels. By introducing four distinct genetic
      changes into the E. coli genome, we have engineered an efficient producer of
      fatty acids. Under fed-batch, defined media fermentation conditions, 2.5 g/L
      fatty acids were produced by this metabolically engineered E. coli strain, with a
      specific productivity of 0.024 g/h/g dry cell mass and a peak conversion
      efficiency of 4.8% of the carbon source into fatty acid products. At least 50% of
      the fatty acids produced were present in the free acid form.

PMID- 18812231
TI  - Lipopolysaccharide differently affects prostaglandin E2 levels in fetal and
      maternal compartments of perfused human term placenta.
AB  - The aim of the present study was to examine the effect of lipopolysaccharide
      (LPS) on the levels of prostaglandin E(2) (PGE(2)) in the perfusates of the fetal
      and the maternal compartments of perfused human term placental tissue. Term
      placentas were perfused for 10h in the absence [control, (n=4)] and presence of
      LPS [LPS=1 microg/kg perfused placental tissue, (n=4)] in the maternal reservoir.
      Perfusate samples from the fetal and the maternal circulations were collected
      every 30 min and examined for PGE(2) levels by radio-immunoassay. PGE(2) levels
      in the fetal circulation were gradually increased reaching significant peak value
      of 479+/-159 pg/ml, as compared to PGE(2) levels in the maternal circulation
      (140+/-146 pg/ml) (p<0.05). After 10 hours of perfusion with control medium,
      PGE(2) levels in the maternal circulation (347+/-144 pg/ml) were significantly
      higher as compared to the fetal circulation (150+/-57 pg/ml) (p<0.05). In
      presence of LPS, PGE(2) levels in the fetal circulation increased reaching a peak
      value of 1028+/-663 pg/ml after 240 min of perfusion. The levels of PGE(2) in the
      control group after 240 min of perfusion were significantly lower (156+/-77
      pg/ml) (p<0.05). No significant differences were detected in the levels of PGE(2)
      in the perfusate of the maternal compartment in presence of LPS, as compared to
      control. Our results suggest that the placenta may play an important role in
      maintaining high levels of PGE(2) in the fetal circulation and low PGE(2) levels
      in the maternal circulation during normal pregnancy. Moreover, placental PGE(2)
      release into the fetal and the maternal circulations may be differently affected
      in presence of intra-uterine infection/inflammation.

PMID- 18812232
TI  - Characterization of endothelial thromboxane receptors in rabbit aorta.
AB  - An increased synthesis of thromboxane (TX) A(2) is associated with a number of
      cardiovascular diseases including atherosclerosis, unstable angina and
      hypertension. We previously identified a subgroup of NZW rabbits in which
      isolated arteries failed to contract to the TX agonists, U46619 or I-BOP. In
      vascular smooth muscle membranes, there was a significant decrease in TX
      receptors, termed TP. These rabbits are referred to as vTP- and those with the TP
      receptor are called vTP+. Because TP receptors are expressed in some types of
      endothelial cells, the present study was designed to determine whether functional
      TP receptors are present in endothelial cells cultured from aortas of vTP+ and
      vTP- rabbits. Radioligand binding studies were performed with (125)I-BOP. Aortic
      endothelial cells from vTP+ rabbits exhibited specific and saturable binding. In
      contrast, in endothelial preparations from vTP- rabbit aortas, no measurable
      binding to (125)I-BOP was detected. Using an anti-TP receptor antibody, we
      compared the amount of receptor expressed in endothelial cell lysates obtained
      from vTP+ and vTP- rabbits. Consistent with the results observed radioligand
      binding assays, the expression of TP receptor protein was decreased in vTP-
      compared to vTP+ endothelial cells. An in vitro wound healing assay was used on
      confluent monolayers of endothelial cells. In the untreated vTP+ cells, the area
      of the scratch was completely closed by 30 h. In the vTP+ cells treated with
      U46619 (3 microM), the rate of closure of the scratch area was reduced with
      approximately 12% of the scratch area remaining at 30 h. Pretreatment with the TP
      receptor antagonist, SQ 29548 (10 microM) prevented the inhibitory effect of
      U46619. The rate of closure of the scratch in the vTP- was not altered by U46619.
      In a separate study, U46619 (3 microM) increased the release of 6-keto
      PGF(1alpha), the stable metabolite of prostacyclin, in vTP+ but not vTP-
      endothelial cells. Pretreatment with SQ29548 (10 microM) or the cyclooxygenase
      inhibitor, indomethacin (10 microM) blocked the increase in vTP+ endothelial
      cells. In vascular reactivity studies in aortas from vTP+ rabbits, removal of the
      endothelium enhanced the vasoconstrictor response to U46619 indicating that
      activation of endothelial TP receptors may modulate vascular tone via the release
      of the vasodilator, prostacyclin. The results of this study suggest an important
      role for endothelial TP receptors in modulating vascular function.

PMID- 18812233
TI  - Microsomal omega-hydroxylated metabolites of N-arachidonoyl dopamine are active
      at recombinant human TRPV1 receptors.
AB  - N-Arachidonoyl dopamine (NADA) is an endogenous lipid that modulates signal
      transduction in neuronal and immune pathways. NADA activates the non-selective
      cation channel, transient receptor potential vanilloid type 1 (TRPV(1)) and
      cannabinoid receptor 1. That NADA is comprised of an arachidonic acid (AA)
      backbone suggests that it may be metabolized through many of the enzymes that act
      upon AA such as the other AA-derived signaling lipids, the endogenous
      cannabinoids. To investigate the metabolism of NADA through the cytochrome P450
      (CYP450) metabolic pathway, we studied the in vitro rat liver microsomal
      production of hydroxylated metabolites and their activity at recombinant human
      TRPV(1) receptors. We showed that following microsomal activation in the presence
      of NADA, omega and (omega-1) hydroxylated metabolites (19- and 20-HETE-DA) were
      formed. These metabolites were active at recombinant human TRPV(1) receptors,
      inducing a dose-dependent calcium influx. Both metabolites exhibited lower
      potency compared to NADA. We conclude that CYP450 enzymes are capable of
      metabolizing this signaling lipid forming a larger family of potential
      neuromodulators.

PMID- 18812234
TI  - Inhibitory effects of epoxyeicosatrienoic acids on volume-activated chloride
      channels in rat mesenteric arterial smooth muscle.
AB  - Epoxyeicosatrienoic acids (EETs) are synthesized from arachidonic acid by
      cytochrome P450 epoxygenases in endothelial cells. It has previously been shown
      that EETs activate K(+) channels, which are important for the hyperpolarization
      and dilation of blood vessels. However, the effects of EETs on other ion channels
      have been less well studied. We investigated the effects of EETs on volume
      activated Cl(-) channels (VACCs) in rat mesenteric arterial smooth muscle cells.
      Whole-cell patch clamp recording demonstrated that hypotonic solution and
      guanosine 5'-[gamma-thio]triphosphate (GTPgammaS) induced a 5-nitro-2-(3
      phenylpropylamino)benzoic acid (NPPB)- and 4,4'-diisothiocyanatostilbene-2,2'
      disulfonic acid (DIDS)-sensitive VACC current in the primary cultured rat
      mesenteric arterial smooth muscle cells. The VACC current was inhibited by EETs
      and the order of potency was 8,9-EET>5,6-EET>11,12-EET>14,15-EET. The inhibitory
      effects of EETs could be reversed by 14,15 epoxyeicosa-5(Z)-enoic acid (14,15
      EEZE, an EET analog), Rp-cGMP and KT-5823 (protein kinase G inhibitors).
      Interestingly, the inhibitory effects of EETs on VACCs were not influenced by Rp
      cAMP (a protein kinase A antagonist) but it could be abolished by NF-449 (a Gs
      protein inhibitor), indicating the involvement of cAMP but not protein kinase A.
      In conclusion, our results demonstrate that EETs inhibit VACCs in rat mesenteric
      arterial smooth muscle cells through a cGMP-dependent pathway, which is probably
      due to the cross-activation by cAMP. This mechanism may be involved in the
      regulation of cell volume and membrane potential.

PMID- 18812235
TI  - Evaluation of the GreenScreen GADD45alpha-GFP indicator assay with non
      proprietary and proprietary compounds.
AB  - The GreenScreen GADD45alpha indicator assay has been assessed for its concordance
      with in vitro genotoxicity and rodent carcinogenicity bioassay data. To test
      robustness, sensitivity, and specificity of the assay, 91 compounds with known
      genotoxicity results were screened in a blinded manner. Fifty seven of the
      compounds were classified as in vitro genotoxic whereas 34 were non-genotoxic.
      Out of the 91 compounds, 50 had been tested in 2-year carcinogenicity assays,
      with 33 identified to be rodent carcinogens and 17 non-carcinogens. Gadd45alpha
      assay sensitivity and specificity for genotoxicity was 30% and 97%, respectively
      (17/57 and 33/34), whereas its sensitivity and specificity for rodent
      carcinogenicity was 30% and 88%, respectively (10/33 and 15/17). Gadd45alpha
      assay genotoxicity results from this validation study exhibited a high
      concordance with previously published results as well as for compound test
      results generated at two different sites (91%, 19/21), indicating that the assay
      is both robust and reproducible. In conclusion, results from this blinded and
      independent validation study indicate that the GreenScreen GADD45 indicator assay
      is reproducible and reliable with low sensitivity and high specificity for
      identifying genotoxic and carcinogenic compounds.

PMID- 18812236
TI  - No association of ABCB1 polymorphisms with drug-refractory epilepsy in a north
      Indian population.
AB  - Multiple drug resistance is a common problem in the treatment of epilepsy, and
      approximately 30% of patients continue to have seizures despite all therapeutic
      interventions. Among various classes of drug transporters, genetic variants of P
      glycoprotein (P-gp) encoded by the ABCB1 (ATP-binding cassette subfamily B member
      1) gene have been associated with drug-refractory epilepsy. Our aim was to
      investigate the effect of the 1236C>T(rs1128503), 2677G>T/A(rs2032582), and
      3435C>T(rs1045642) single-nucleotide polymorphisms of ABCB1 (or MDR1) on drug
      resistance in north Indian patients with epilepsy. Genotyping was performed in
      101 control subjects and 325 patients with epilepsy, of whom 94 were drug
      resistant and 231 drug responsive. Therapeutic drug monitoring for phenytoin,
      carbamazepine, phenobarbital, and valproate was also performed to confirm
      compliance in 20% of the patients. Genotype and haplotype frequencies of these
      polymorphisms did not differ between drug-resistant and drug-responsive patients.
      Our results demonstrate ABCB1 polymorphisms are not associated with drug
      resistance in north Indian epileptic patients.

PMID- 18812237
TI  - Re: Recombinant human hepatocyte growth factor for liver failure.

PMID- 18812238
TI  - Investigations into charge heterogeneity of wool intermediate filament proteins.
AB  - Genomic studies have shown that there are four abundant type I and type II
      intermediate filament proteins (IFPs) in wool. When separated using 2D-PAGE, the
      type I IFPs separated into four clearly defined major rows. The type II IFPs
      separated into two distinct staggered rows. The large number of spots seen by 2D
      PAGE has previously been attributed to charge heterogeneity caused by post
      translational modification of the protein. However, analysis of wool IFPs by 2D
      PAGE techniques and mass spectrometry suggested an absence of phosphorylation or
      glycosylation modifications. Investigations with both the type I and type II IFPs
      showed that when single protein spots from a 2D-PAGE separation are eluted, re
      focused and re-electrophoresed, several spots are formed on both the acidic and
      basic side of the original spot. Amino acid analysis, mass spectrometry and
      Ellman's assay support the hypothesis that the proteins have the same sequence
      but vary in isoelectric charge, due to differences in exposure of charged
      residues on the molecular surface. The cause of IFP charge heterogeneity is thus
      proposed to be a conformational equilibrium between several different forms of
      the same protein in the rehydration solution used for the first dimension.

PMID- 18812239
TI  - Aqueous solutions of transition metal containing micelles.
AB  - Incorporation of d- or f-block metals into ligand systems that renders a metal
      complex surface-active or drives its partitioning into surfactant phases enables
      the localisation of chemical functionality at interfaces. This article discusses
      a number of fundamental aspects of these interesting materials and examines
      potential applications.

PMID- 18812240
TI  - Synthesis of fructofuranosides: efficient glycosylation with N
      phenyltrifluoroacetimidate as the leaving group.
AB  - Fructofuranosyl trifluoroacetimidate 3 was demonstrated to be an effective
      glycosyl donor that exhibited good alpha-selectivity and good yield in
      fructosylation reactions. The reaction proceeds via neighboring group
      participation, which was proved by the isolation of a stable allylic orthoester
      intermediate.

PMID- 18812241
TI  - Effects of hormone therapy with estrogen and/or progesterone on sleep pattern in
      postmenopausal women.
AB  - OBJECTIVE: To investigate the effects of estrogen and progesterone on sleep in
      postmenopausal women. METHOD: The 33 participants were randomly assigned to an
      estrogen or placebo group after undergoing clinical and hormonal assessments and
      a polysomnogram, and they underwent the same tests again after 12 weeks. Then,
      while still taking estrogen or placebo, they all received progesterone for
      another 12 weeks and underwent a final polysomnogram. RESULTS: Estrogen plus
      progesterone was more effective than estrogen alone in decreasing the prevalence
      of periodic limb movement (PLM) (8.1% vs 2.8%), hot flashes (14.2% vs 0%), and
      bruxism (11.1% vs 0%) at night, or somnolence and attention difficulty during the
      day. The prevalences of breathing irregularities, arousal from sleep, anxiety,
      and memory impairment were decreased in both groups following progesterone
      treatment. CONCLUSION: While not significantly affecting sleep quality, hormone
      therapy decreased the prevalence of arousal in both groups and that of PLM in the
      group treated with estrogen plus progesterone.

PMID- 18812242
TI  - Use of healthcare services and risk factors among pregnant women in Crete.

PMID- 18812243
TI  - Indications for gynecologic surgery and their implications for sexual function in
      menopausal women.
AB  - OBJECTIVE: To determine the indications for gynecologic surgery and the effect of
      surgery on dyspareunia and sexual intercourse frequency in menopausal women in
      Accra, Ghana. METHOD: Women who had gynecologic surgery between January 2005 and
      December 2007 were invited for an interview about dyspareunia and frequency of
      intercourse before and after surgery. RESULTS: Of the 93 women interviewed who
      underwent hysterectomy, 29 (31.1%) had dyspareunia before surgery and 13 (14.0%)
      after (P=0.006). Of the 65 women who had benign tumors, before surgery 26 (40%)
      were sexually active, while after surgery 43 (66%) were sexually active
      (P=0.001). However, frequency of intercourse did not change for those with
      malignancies. The mean frequency of intercourse before surgery was 2.11 per week,
      compared with 2.46 per week after surgery (P=0.50). CONCLUSION: Gynecologic
      surgery reduced dyspareunia. More women became sexually active following surgery
      for benign but not malignant tumors, but the mean overall frequency of
      intercourse did not change significantly in the interviewed population.

PMID- 18812244
TI  - Harmonic scalpel versus conventional electrosurgery in the treatment of vulvar
      cancer.
AB  - OBJECTIVE: To compare differences in blood loss, operative time, and intra- and
      postoperative complications with the harmonic scalpel or conventional
      electrosurgery in the treatment of vulvar cancer. METHODS: Consecutive patients
      who underwent radical vulvectomy with inguinal lymphadenectomy using the harmonic
      scalpel (HS) or conventional electrosurgery (CE) were compared. RESULTS: A total
      of 42 patients were included, 22 in the HS group and 20 in the CE group. Mean
      blood loss was significantly less in the HS group compared with the CE group (127
      mL vs 210 mL; P<0.05) and mean operative time was significantly shorter with the
      HS compared with CE (117 minutes vs 142 minutes; P<0.05). There were no
      significant differences between the 2 groups in postoperative complications.
      CONCLUSION: Use of the harmonic scalpel for surgical treatment of vulvar cancer
      is safe and has several advantages, including decreased operative time and blood
      loss, improved visibility in the operative field, and good postoperative outcome.

PMID- 18812245
TI  - Quantitative fluorescent polymerase chain reaction to detect chromosomal
      anomalies in spontaneous abortion.
AB  - OBJECTIVES: To evaluate the value of short tandem repeats (microsatellites) in
      the study of numerical chromosomal anomalies in spontaneous abortion. METHOD:
      Multiplex quantitative fluorescent polymerase chain reaction (QF-PCR) was carried
      out on 61 spontaneous abortion samples and 48 controls using microsatellite
      markers from 8 chromosomes where aneuploids are commonly found. RESULTS: Of the
      61 samples, 65.6% were successfully karyotyped, and the call rate of the QF-PCR
      was 98.3%. The correspondence between PCR and karyotyping was 95%. The success
      rate of karyotyping in the inevitable abortion group was 79.6%, higher than for
      the missed abortion group (8.3%), P<0.001. The call rate of QF-PCR showed no
      difference between these 2 groups (100% vs 91.7%, P=0.197). CONCLUSION:
      Microsatellite-based QF-PCR is a helpful and reliable tool to diagnose numerical
      chromosomal anomalies in spontaneous abortion. It also provides a diagnosis for
      necrotic tissue.

PMID- 18812246
TI  - Sexual violence-related fistulas in the Democratic Republic of Congo.
AB  - OBJECTIVE: To determine the magnitude of traumatic gynecologic fistulas caused by
      sexual violence in the Democratic Republic of Congo. METHODS: A retrospective
      analysis of hospital records from 604 consecutive patients who received treatment
      for gynecologic fistulas at Panzi Hospital between November 2005 and November
      2007. RESULTS: Of the 604 patients, 24 (4%) reported that their fistulas had been
      caused by sexual violence; of these, 5 (0.8%) had developed fistulas as a direct
      result of forced penetration with foreign objects and/or gang rapes. Of the
      remaining patients, 6 had a fistula before they were raped, 9 developed
      iatrogenic fistulas following inappropriate instrumentation to manage rape
      induced spontaneous abortion or stillbirth, or after abdominal hysterectomy, and
      4 developed fistulas after prolonged and obstructed labor. CONCLUSION: Traumatic
      fistulas are rare compared to obstetric fistulas. Fistulas indirectly related to
      sexual violence are likely to be more common than those directly related. All
      fistulas resulting from sexual violence, whether direct or indirect, should be
      considered traumatic and special care should be given to these women.

PMID- 18812247
TI  - Children do not follow the rule "ignorance means getting it wrong".
AB  - Two experiments tested whether 4- and 5-year-olds follow the rule "ignorance
      means you get it wrong." Following this rule should lead children to infer that a
      character who is ignorant about some situation will also have a false belief
      about it. This rule should sometimes lead children into error because ignorance
      does not imply false belief. In Experiment 1, children and adults were told about
      a girl who is looking for her dog but does not know which of two boxes it is
      under. Most children predicted that the girl would look in the box with the dog
      and not in the empty box; adults chose both boxes equally. Experiment 2 used a
      similar story but varied whether the girl wants to approach or avoid her dog.
      Again, most children predicted that the girl would succeed. These findings
      suggest that children do not follow the rule "ignorance means you get it wrong."

PMID- 18812248
TI  - Grevillosides A-F: glucosides of 5-alkylresorcinol derivatives from leaves of
      Grevillea robusta.
AB  - From a MeOH extract of leaves of Grevillea robusta, seven compounds (1-7) were
      isolated. One known compound (7) was identified with a benzyl glucoside,
      icariside F2. The structures of the six of these, named grevillosides A-F (1-6),
      were elucidated on detailed inspection of one- and two-dimensional NMR
      spectroscopic data as glucosides of 5-alkylresorcinols.

PMID- 18812249
TI  - Study of the toxicity of diuron and its metabolites formed in aqueous medium
      during application of the electrochemical advanced oxidation process "electro
      Fenton".
AB  - Diuron (N'-[3,4-dichlorophenyl]-N,N-dimethylurea) is a herbicide belonging to the
      phenylurea family, widely used to destroy weeds on uncultivated surfaces. Because
      of its toxicity for aquatic organisms and suspicion of being carcinogenic for
      humans, diuron is the object of growing environmental concern. Therefore, we have
      developed the electro-Fenton method, an electrochemical advanced oxidation
      process (EAOP), to degrade diuron in aqueous medium, and we have studied the
      evolution of the toxicity of treated solution during the process. Indeed, the
      EAOPs catalytically generate hydroxyl radicals that oxidize the persistent
      organic pollutants, and can ultimately destroy and mineralize them. But,
      sometimes, relatively toxic organic metabolites are formed during the oxidation
      reaction. In this work, the evolution of toxicity of diuron aqueous solutions was
      studied at different initial concentrations, during treatment by the electro
      Fenton method. Samples were collected at various electrolysis times and
      mineralization degrees during the treatment. The toxicity of the samples was
      measured using the bacteria Vibrio fischeri (Microtox) and the green alga
      Scenedesmus obliquus. Our results demonstrated that the toxicity of diuron
      aqueous solutions (concentrations=3.0-27.6 mg L(-1)) varied considerably with
      time. The formation and disappearance of several metabolites, having toxicity
      often stronger than that of the initial herbicide, were observed. To improve the
      efficiency of water decontamination, the electro-Fenton method should be applied
      during a time long enough (several hours) and at relatively high electrolysis
      current (I=250 mA) to reach a nearly complete mineralization of the herbicide in
      the aqueous medium.

PMID- 18812250
TI  - Oxidative transformation of aqueous phenolic mixtures by birnessite-mediated
      catalysis.
AB  - The catalytic efficiency of birnessite in the removal of catechol,
      hydroxytyrosol, methylcatechol and m-tyrosol, four phenols commonly present in
      polluted wastewaters, was studied in mono-substrate solutions or in mixtures of
      two, three, and four substrates. In single phenolic solutions the transformation
      order of phenols was catechol>hydroxytyrosol>methylcatechol>m-tyrosol. With
      phenolic mixtures different responses were observed and the amount of each phenol
      transformed and the crossing effects among the various phenols depended on the
      type and number of phenols present in the mixture. In particular, general
      inhibitory effects were observed for hydroxytyrosol and m-tyrosol that were
      transformed less when present in combination with the other phenols. By contrast
      the effects by the presence of more than one phenol were basically annulled for
      catechol and methylcatechol at 24 h incubation in all the mixtures. A
      simultaneous, but often no stoichiometric, release of soluble Mn2+ in the
      reaction mixtures occurred. The multi-substrate systems were designed to mimic
      birnessite-mediated oxidative processes that could occur under field conditions.
      Therefore they could be of great interest to environmental and soil science. The
      use of birnessite as a potential tool for an effective detoxification and
      recovery of phenol-polluted systems could be also envisaged.

PMID- 18812251
TI  - Inter-strain differences in glucocorticoid and mineralocorticoid effects on
      macrophage and lymphocyte functions in mice.
AB  - We showed previously and we confirm here that macrophages from three mouse
      strains are differentially sensitive to the inhibition of expression of key
      inflammatory proteins (iNOS-II, IL-1 beta) by dexamethasone, a specific
      glucocorticoid receptor agonist (C57BL/6>DBA/2>BALB/c). Here we show that
      aldosterone (a specific mineralocorticoid agonist) has no effect on iNOS-II or IL
      1 beta expression in macrophages from these mouse strains but decreases IL-1ra
      expression, with small inter-strain differences. This mechanism may be involved
      in the pro-inflammatory effect of this hormone. Concanavalin A-stimulated
      lymphocytes proliferation is also differentially sensitive to dexamethasone
      according to the strain, but insensitive to aldosterone.

PMID- 18812252
TI  - A qualitative and a quantitative analysis of an auto-segmentation module for
      prostate cancer.
AB  - PURPOSE: This work describes the clinical validation of an automatic segmentation
      algorithm in CT-based radiotherapy planning for prostate cancer patients.
      MATERIAL AND METHODS: The validated auto-segmentation algorithm (Smart
      Segmentation, version 1.0.05) is a rule-based algorithm using anatomical
      reference points and organ-specific segmentation methods, developed by Varian
      Medical Systems (Varian Medical Systems iLab, Baden, Switzerland). For the
      qualitative analysis, 39 prostate patients are analysed by six clinicians.
      Clinicians are asked to rate the auto-segmented organs (prostate, bladder, rectum
      and femoral heads) and to indicate the number of slices to correct. For the
      quantitative analysis, seven radiation oncologists are asked to contour seven
      prostate patients. The individual clinician contour variations are compared to
      the automatic contours by means of surface and volume statistics, calculating the
      relative volume errors and both the volume and slice-by-slice degree of support,
      a statistical metric developed for the purposes of this validation. RESULTS: The
      mean time needed for the automatic module to contour the four structures is about
      one minute on a standard computer. The qualitative evaluation using a score with
      four levels ("not acceptable", "acceptable", "good" and "excellent") shows that
      the mean score for the automatically contoured prostate is "good"; the bladder
      scores between "excellent" and "good"; the rectum scores between "acceptable" and
      "not acceptable". Using the concept of surface and volume degree of support, the
      degree of support given to the automatic module is comparable to the relative
      agreement among the clinicians for prostate and bladder. The slice-by-slice
      analysis of the surface degree of support pinpointed the areas of disagreement
      among the clinicians as well as between the clinicians and the automatic module.
      CONCLUSION: The efficiency and the limits of the automatic module are
      investigated with both a qualitative and a quantitative analysis. In general,
      with efficient correction tools at hand, the use of this auto-segmentation module
      will lead to a time gain for the prostate and the bladder; with the present
      version of the algorithm, modelling of the rectum still needs improvement. For
      the quantitative validation, the concept of relative volume error and degree of
      support proved very useful.

PMID- 18812253
TI  - Youths' understandings of cigarette advertisements.
AB  - This study addresses two questions: (1) when youths are exposed to advertisements
      for cigarettes, do they primarily see advertisements for brands or products, and
      (2) is there a relationship between youths' understandings of cigarette
      advertisements and their susceptibility to smoking? A sample of 271 participants
      ranging in age from 7 to 12 viewed a series of print advertisements that included
      cigarette and non-tobacco-related ads. While viewing each ad, participants were
      asked to indicate what they thought the advertisement was trying to sell.
      Responses were coded into one of three categories reflecting important
      differences in participants' comprehension of each advertisement - no
      understanding, product category understanding, or brand understanding. Results
      show that youths typically understand the type of product an advertisement is
      promoting; however, the levels of brand understanding observed for cigarette
      advertisements were low in an absolute sense, and significantly lower than brand
      understanding of non-tobacco-related advertisements. Results also show that
      understanding cigarette ads as promoting specific brands of cigarettes is
      positively related to susceptibility to smoking. Taken together, these findings
      provide a glimpse of the psychological mechanisms that may underlie the well
      established link between exposure to cigarette advertising and youth smoking.

PMID- 18812254
TI  - Dark therapy for schizoaffective disorder. A case report.

PMID- 18812255
TI  - A phase II study of irinotecan in children with relapsed or refractory
      neuroblastoma: a European cooperation of the Societe Francaise d'Oncologie
      Pediatrique (SFOP) and the United Kingdom Children Cancer Study Group (UKCCSG).
AB  - PURPOSE: To evaluate the efficacy and safety of irinotecan in paediatric
      recurrent or refractory neuroblastoma. PATIENTS AND METHODS: Thirty seven
      patients aged between 6 months and < or = 20 years, with relapsed or refractory
      neuroblastoma, received irinotecan at 600 mg/m(2) administered as a 60-min
      infusion, every 3 weeks. Tumour response was evaluated by conventional
      radiological and mIBG scans every two cycles. RESULTS: No objective response was
      observed during the study. Stable disease was observed in 13% of evaluable
      patients. Median times to progression and survival were 1.4 months (range, 1.2
      1.5 months) and 8.8 months (range, 6.7-11.3 months), respectively. One forty two
      cycles were administered, with a median of two cycles per patient (range, 1-17
      cycles). The most common grade 3-4 toxicities were neutropenia (65% of patients),
      anaemia (43%), thrombocytopenia (38%), vomiting (14%), abdominal pain or cramping
      (8%), and nausea (5%). CONCLUSION: Irinotecan administered intravenously as a
      single agent every 3 weeks induced no objective response in relapsed or
      refractory neuroblastoma.

PMID- 18812256
TI  - Using proton nuclear magnetic resonance to study the mode of ribonuclease A
      inhibition by competitive and noncompetitive inhibitors.
AB  - The C(2) proton resonances of the active site histidines (His 12 and His 119) of
      ribonuclease A have been exploited to study the inhibition pattern of both
      noncompetitive (four green tea polyphenols and their copper complexes) and
      competitive (3'-O-carboxy esters of thymidine and 3'-amino derivatives of
      uridine) inhibitors. Competitive inhibitors devoid of any phosphate group have
      the ability to change the pK(a) of the histidine residues at the active site.
      Their mode of inhibition, albeit competitive, is found to be different compared
      to known phosphate inhibitors 2'-CMP and 3'-CMP as revealed by changes in the
      pK(a) values. We find a correlation between the changes in the chemical shift of
      His 12 and the corresponding inhibition constants (K(i)).

PMID- 18812257
TI  - Synthesis of potent water-soluble tissue transglutaminase inhibitors.
AB  - Dipeptide-based sulfonium peptidylmethylketones derived from 6-diazo-5-oxo-L
      norleucine (DON) have been investigated as potential water-soluble inhibitors of
      extracellular transglutaminase. The lead compounds were prepared in four steps
      and exhibited potent activity against tissue transglutaminase.

PMID- 18812258
TI  - Site-specific self-cleavage of G-quadruplexes formed by human telemetric repeats.
AB  - It is demonstrated in our investigations that certain G-quadruplex structures
      formed by human telomeric repeats could perform self-cleaving actions. Our
      further studies verify that these reactions are site-specific and undergo
      hydrolytic pathways.

PMID- 18812259
TI  - 3-(Imidazolyl methyl)-3-aza-bicyclo[3.1.0]hexan-6-yl)methyl ethers: a novel
      series of mGluR2 positive allosteric modulators.
AB  - The synthesis and structure-activity relationship (SAR) of a novel series of 3
      (imidazolyl methyl)-3-aza-bicyclo[3.1.0]hexan-6-yl)methyl ethers, derived from a
      high throughput screening (HTS), are described. Subsequent optimization led to
      identification of potent, metabolically stable and orally available mGluR2
      positive allosteric modulators (PAMs).

PMID- 18812260
TI  - Synthesis and properties of 3'-amino-2',4'-BNA, a bridged nucleic acid with a N3'
      ->P5' phosphoramidate linkage.
AB  - The synthesis and properties of a bridged nucleic acid analogue containing a N3'-
      >P5' phosphoramidate linkage, 3'-amino-2',4'-BNA, is described. A heterodimer
      containing a 3'-amino-2',4'-BNA thymine monomer, and thymine and methylcytosine
      monomers of 3'-amino-2',4'-BNA and their 5'-phosphoramidites, were synthesized
      efficiently. The dimer and monomers were incorporated into oligonucleotides by
      conventional 3'-->5' assembly, and 5'-->3' reverse assembly phosphoramidite
      protocols, respectively. Compared to a natural DNA oligonucleotide, modified
      oligonucleotides containing the 3'-amino-2',4'-BNA residue formed highly stable
      duplexes and triplexes with single-stranded DNA (ssDNA), single-stranded RNA
      (ssRNA), and double-stranded DNA (dsDNA) targets, with the average increase in
      melting temperature (T(m)) against ssDNA, ssRNA and dsDNA being +2.7 to +4.0
      degrees C, +5.0 to +7.0 degrees C, and +5.0 to +11.0 degrees C, respectively.
      These increases are comparable to those observed for 2',4'-BNA-modified
      oligonucleotides. In addition, an oligonucleotide modified with a single 3'-amino
      2',4'-BNA thymine residue showed extraordinarily high resistance to nuclease
      degradation, much higher than that of 2',4'-BNA and substantially higher even
      than that of 3'-amino-DNA and phosphorothioate oligonucleotides. The above
      properties indicate that 3'-amino-2',4'-BNA has significant potential for
      antisense and antigene applications.

PMID- 18812261
TI  - The molecular interactions of buspirone analogues with the serotonin transporter.
AB  - A major problem with the selective serotonin reuptake inhibitors (SSRIs) is the
      delayed onset of action. A reason for that may be that the initial SSRI-induced
      increase in serotonin levels activates somatodendritic 5-HT(1A) autoreceptors,
      causing a decrease in serotonin release in major forebrain areas. It has been
      suggested that compounds combining inhibition of the serotonin transport protein
      with antagonistic effects on the 5-HT(1A) receptor will shorten the onset time.
      The anxiolytic drug buspirone is known as 5-HT(1A) partial agonist. In the
      present work, we are studying the inhibition of the serotonin transporter protein
      by a series of buspirone analogues by molecular modelling and by experimental
      affinity measurements. Models of the transporter protein were constructed using
      the crystal structure of the Escherichia coli major facilitator family
      transporter-LacY and the X-ray structure of the neurotransmitter symporter family
      (NSS) transporter-LeuT(Aa) as templates. The buspirone analogues were docked into
      both SERT models and the interactions with amino acids within the protein were
      analyzed. Two putative binding sites were identified on the LeuT(Aa) based model,
      one suggested to be a high-affinity site, and the other suggested to be a low
      affinity binding site. Molecular dynamic simulations of the LacY based model in
      complex with ligands did not induce a helical architecture of the LacY based
      model into an arrangement more similar to that of the LeuT(Aa) based model.

PMID- 18812262
TI  - A highly efficient biomimetic aromatization of Hantzsch-1,4-dihydropyridines with
      t-butylhydroperoxide, catalysed by iron(III) phthalocyanine chloride.
AB  - Rapid aromatization of Hantzsch-1,4-DHPs with t-butylhydroperoxide catalysed by
      iron(III) phthalocyanine chloride is described. The reaction proceeds smoothly at
      room temperature within 1-35 min and the products of high purity were isolated in
      excellent yields. To explain the reactivity of this catalytical system plausible
      mechanism have been proposed to involve formation of high-valent oxoferryl
      species as in cytochrome P450 itself.

PMID- 18812263
TI  - Race/ethnic variation in serum levels of IGF-I and IGFBP-3 in US adults.
AB  - OBJECTIVES: The IGF axis plays a significant role in normal growth and
      development and variation in IGFs is associated with health outcomes. Past
      studies report variation in IGF levels among race/ethnic groups known to differ
      in disease incidence. This paper reports on race/ethnic variation in serum levels
      of IGF-I and IGF-BP3 in a nationally representative and ethnically diverse sample
      of US adults. DESIGN: Serum IGF-I and IGFBP-3 levels from the fasting subsample
      (n = 6061) of respondents to the US National Health and Nutrition Examination
      Survey III (NHANES III) were analyzed using an IGF-I ELISA (Diagnostic Systems
      Laboratory (DSL) 10-5600) and an IGFBP-3 IRMA (DSL 6600). The NHANES is a
      combined examination and interview survey of a nationally representative sample
      of US adults. Regression analyses were used to estimate cross-sectional
      associations between the IGF axis and demographic variables. RESULTS: In
      unadjusted analyses, serum IGF-I levels were higher in males than in females, and
      IGFBP-3 levels were higher in females than in males. Both analytes were lower in
      older adults. Univariate analyses indicate that serum levels of IGF-I are lower
      in female Non-Hispanic Whites (NHW) (256 [4.9]) and Hispanics (249 [6.6]) than in
      Non-Hispanic Blacks (NHB) (281 [4.9]). However, in males, IGF levels in NHWs (287
      [3.6]) and NHBs (284 [4.3]) are similar and levels in Mexican-Americans are only
      moderately reduced (265 [3.4]). Notably, NHB's have the highest molar ratio of
      IGF-I:IGFBP-3 at all ages. After adjustment for age and BMI, gender and
      race/ethnicity differences persist. CONCLUSIONS: These cross-sectional data
      support exploration of the IGF axis as an explanation for some race/ethnic
      differences in cancer incidence.

PMID- 18812264
TI  - Ultrasonic dyeing of cationized cotton fabric with natural dye. Part 1:
      cationization of cotton using Solfix E.
AB  - The dyeing of cationized cotton fabric with Solfix E using colouring matter
      extracted from Cochineal dye has been studied using both conventional and
      ultrasonic techniques. Factors affecting dye extraction such as ultrasound power,
      particle size, extraction temperature and time were studied. The results
      indicated that the extraction by ultrasound at 300 W was more effective at lower
      temperature and time than conventional extraction. The effect of various factors
      of dye bath such as pH, salt concentration, ultrasound power, dyeing time and
      temperature were investigated. The colour strength values obtained were found to
      be higher with ultrasound than with conventional techniques. The results of
      fastness properties of the dyed fabrics were fair to good. The scanning electron
      microscope (SEM) images of the morphological and X-ray analyzes were measured for
      cationized cotton fabrics dyed with both conventional and ultrasound methods,
      thus showing the sonicator efficiency.

PMID- 18812265
TI  - Analysis of depth of anesthesia with Hilbert-Huang spectral entropy.
AB  - OBJECTIVE: Monitoring the effect of anesthetic drug on the neural system is an
      ongoing challenge for anesthetists. Several methods based on the
      electroencephalogram (EEG) have been proposed to estimate the depth of anesthesia
      (DoA); for instance, the Fourier-based time-frequency balanced spectral entropy
      as implemented in the Datex-Ohmeda M-Entropy Module. In this paper, a novel
      method based on Hilbert-Huang transform is proposed to calculate a spectral
      entropy value, called Hilbert-Huang spectral entropy and is applied to EEG
      recordings during sevoflurane anesthesia. The dose-response relation of Hilbert
      Huang spectral entropy during sevoflurane anesthesia is presented. METHODS: We
      analyzed a previously collected set of EEG data, obtained from 14 patients'
      during the induction of general anesthesia with sevoflurane. The Hilbert-Huang
      spectral entropy and the Datex-Ohmeda M-Entropy were applied to the EEG
      recording. State entropy and response entropy based on the Hilbert-Huang spectral
      entropy and the Datex-Ohmeda M-Entropy were calculated, respectively. The
      performance of both methods was assessed by pharmacokinetic/pharmacodynamic
      modeling and prediction probability. To obtain reliable Hilbert-Huang spectral
      entropy and Datex-Ohmeda M-Entropy values, a combined preprocessor was applied in
      advance. RESULTS: In the awake state, the baseline variability (as estimated by
      the coefficient of variation) of the Hilbert-Huang spectral entropy was less than
      half the variability of the Datex-Ohmeda M-Entropy (p<0.001). All entropy values
      decreased similarly with increasing sevoflurane concentration, as shown by the
      high correlation between the respective methods (p<0.001). However, Hilbert-Huang
      spectral entropy exhibited greater resistance to noise in the EEG signal; and
      decreased in a more linear fashion with increasing sevoflurane effect-site
      concentration, particularly around the point of loss of consciousness. The
      goodness-of-fit of the pharmacokinetic/pharmacodynamic model and the prediction
      probability using the state entropy of Hilbert-Huang spectrum (R2=0.86,
      P(k)=0.84) was significantly better than that using the one of M-Entropy
      (R2=0.80, P(k)=0.81, p<0.05); however, the difference between response entropy
      values was not statistically significant. CONCLUSION: The results from this small
      dataset suggest that the Hilbert-Huang spectral entropy has a slightly stronger
      ability to track changes in sevoflurane effect-site concentration than M-Entropy
      with a stronger noise-resistance. SIGNIFICANCE: Hilbert-Huang spectral entropy
      could be incorporated in the design of a new method to estimate the effect of
      anesthetic drugs on the EEG.

PMID- 18812266
TI  - Independent component analysis of subdurally recorded occipital seizures.
AB  - OBJECTIVE: To study the components of occipital seizures using independent
      component analysis (ICA) of subdurally recorded electroencephalogram (EEG) data.
      METHODS: Twenty-seven subdurally recorded occipital seizures from eight patients
      were studied. ICA was performed, and the resulting independent components (ICs)
      were compared with respect to their power, frequency, degree of spread within the
      epileptogenic zone, and propagation patterns. The ictal ICs were further
      subdivided into propagating and non-propagating types. RESULTS: ICA provided
      information over and above that supplied by standard visual EEG analysis,
      confirming that all the seizures originated in the occipital lobe, and affording
      additional knowledge regarding the nature of the seizure onset zone. Each seizure
      was composed of multiple ICs, some of which propagated while others remained
      within the epileptogenic zone. There was no statistical difference between the
      propagating and non-propagating ICs with respect to power or frequency. However,
      propagating ICs involved a significantly greater number of recording electrodes
      at their onset when compared to the non-propagating ICs. CONCLUSIONS: The
      propagation likelihood of ICs in occipital seizures is independent of their power
      or frequency, but it is dependent on the volume of brain giving rise to that
      signal; ICs that are generated by a greater volume of brain within the
      epileptogenic zone are more likely to propagate. SIGNIFICANCE: This study shows
      that ICA has the potential to be used to redefine the epileptogenic zone and
      guide the extent of cortisectomy for the treatment of patients with medically
      intractable occipital epilepsy.

PMID- 18812268
TI  - Pre-surgical high resolution ultrasound of facial basal cell carcinoma:
      correlation with histology.
AB  - The aim of this study was to analyze the scope of pre-surgical high resolution
      ultrasound in basal cell carcinoma (BCC). BCC is the most common human cancer.
      According to recent large prospective studies incomplete excision of BCC is
      higher than expected. Pre-operative imaging may aid surgical planning by
      identifying the extent and location of a neoplasm, which can be interesting at
      zones with higher risk of recurrences such as the face. These are slow growing
      tumors but there are some aggressive types described that can involve deeper
      structures. Twenty-five patients were studied (10 F/15 M, 48-91 years old; mean
      age 69.5+/-11.5 years) with suspicious facial lesions < or =1.5 cm. Pre-surgical
      ultrasound with compact linear 15-7 MHz probe was performed. Ultrasound reported
      the morphology and thickness of the tumors. The results were correlated with the
      histology. Ultrasound identified 29 suspicious facial lesions that were removed
      with tumor-free borders at the first surgery and confirmed by histology. The main
      location was the nose. Two subclinical satellite lesions at the nasal zone were
      detected under ultrasound which led to a change in the surgery plan. The
      intraclass correlation coefficient (ICC) value was used to compare tumor
      thickness measurements between ultrasound and histology. ICC was considered as
      very good (0.9). Therefore, ultrasound can be useful to plan BCC surgery, it can
      recognize lesions, layers of involvement and vascularity patterns in a non
      invasive way. It can show subclinical satellite lesions, even though the number
      of subclinical cases is small and require further investigations. It has a good
      thickness correlation with histology and may be used as a technique to monitor
      disease changes following non-invasive medical treatments in the future.

PMID- 18812269
TI  - The hostile abdomen--a systematic approach to a complex problem.

PMID- 18812270
TI  - Trends in surgical wound healing.
AB  - The understanding of acute and chronic wound pathophysiology has progressed
      considerably over the past decades. Unfortunately, improvement in clinical
      practice has not followed suit, although new trends and developments have
      improved the outcome of wound treatment in many ways. This review focuses on
      promising clinical development in major wound problems in general and on
      postoperative infections in particular.

PMID- 18812271
TI  - Long-term results of laparoscopic Nissen fundoplication due to gastroesophageal
      reflux disease. A ten year follow-up in a low volume center.
AB  - BACKGROUND AND AIMS: Laparoscopic 360 degrees nissen fundoplication has been our
      routine surgical procedure since 1995, in the treatment of gastroesophageal
      reflux disease (GERD). We have reviewed our results of patients treated with
      laparoscopic Nissen fundoplication (LNF) during 1995-1998. MATERIAL AND METHODS:
      170 patients have undergone LNF in our hospital since 1995. during the period of
      1995-1998, 33 patients were treated. all patients were asked to return a
      structured follow-up questionnaire, using a Visick grading scale, after an
      average of 69 months (2003) and 117 months (2007). 29 questionnaires (90%) were
      answered in 2003, and 31 questionnaires (97%) were answered in 2007. one patient
      died at home before the first questionnaire in 2003, and is therefore not
      included. We present our results on LNF after an observation time of 117 months
      (range 99-144 months). RESULTS: patient satisfaction after LNF is rated as very
      good or good (Visick 1-2) in 93% in 2003 and 97% in 2007. 97% of the patients
      would recommend the same treatment to other patients with similar symptoms at ten
      year follow up. One patient has undergone resurgery during follow up. Daily gas
      bloat and flatulence is reported in 52% in 2003 and 39% in 2007, and is the most
      common reason for reduced satisfaction. Five patients report of reflux symptoms,
      one patient daily and four patients sometimes, where the first patient still uses
      proton pump inhibitor (PPI) daily and three patients use PPI occasionally.
      CONCLUSIONS: patient satisfaction after LNF treatment for gerd is high at long
      term (10 years) follow-up. Bloating and flatulence persistently occurred to a
      great extent and the need for preoperative information regarding these symptoms
      is important.

PMID- 18812272
TI  - Low local recurrence rates after rectal cancer resection with limited use of
      preoperative radiotherapy.
AB  - BACKGROUND: Local recurrence rates after curative rectal resection for rectal
      cancer have decreased after introduction of TME. In order to achieve even further
      reduction in local recurrence rates, several hospitals increase the use of
      preoperative radiotherapy. Thus, therapy-related side effects will increase. The
      aim of the study was to evaluate the results of the TME-technique with minimal
      use of radiotherapy. MATERIALS AND METHODS: a prospective observational study
      from 1993 to 2000 of 137 consecutive patients treated for rectal cancer at the
      department of surgery, Nordland Hospital HF, Bodo, Norway. RESULTS: 115 patients
      underwent curative resections (84%). eight patients (6.4 %) received peri
      operative radiotherapy: three preoperatively (2.4%) because of clinically fixed
      tumours and five patients (4%) postoperatively; four with pR1-resections and one
      patient after perforation of the rectum. The local recurrence rate was 3.4 % with
      an observation time of 5 years. The total survival rate was 74% in curative
      group. In 22 patients the treatment was palliative. Only one of these patient
      survived 5 years. CONCLUSION: With TME-technique it is possible to achieve low
      recurrence rates and high survival rates with a high curative rate with minimal
      use of additional radiotherapy.

PMID- 18812273
TI  - Local staging of rectal cancer using the black lumen magnetic resonance imaging
      technique.
AB  - BACKGROUND AND AIMS: The treatment of rectal cancer is comprised of surgery and
      possible adjuvant therapy depending on the stage of the tumour. This prospective
      study evaluates the accuracy of magnetic resonance imaging (MRI) in the
      preoperative staging of rectal cancer using an endorectal and intravenous
      contrast. MATERIALS AND METHODS: 37 consecutive patients with rectal cancer were
      imaged using a mixture of ferumoxsil and methylcellulose endorectally, and a
      gadolinium contrast intravenously. 33 tumours were resected and 4 tumours were
      considered unresectable during operation. The images were reviewed for local
      staging of the tumours. A tumour confined to the rectal wall was classified as a
      negative finding and a tumour invading through muscularis propria as a positive
      finding. The results were correlated with the histopathologic t stage (n = 33),
      or the clinical status (n = 4). RESULTS AND CONCLUSIONS: of 37 cases, 20 (51 %)
      were true positive, and 11 (28%) were true negative. There were 3 false negative
      and 3 false positive cases. The sensitivity was 87%, specificity 79%, and
      diagnostic accuracy 84%. for the non-contrast images the figures were 78%, 79%
      and 78%, respectively. We consider black lumen magnetic resonance imaging to be a
      useful method for preoperative local staging of rectal cancer.

PMID- 18812274
TI  - Pancreatic injuries in the United Arab Emirates.
AB  - PURPOSE: To study the mechanism, management and outcome of patients who had
      sustained pancreatic trauma. METHODOLOGY: Patients who were treated for
      pancreatic trauma in Al-Ain Hospital between October 2002 and August 2007 were
      retrospectively studied. RESULTS: All eleven patients were males having a median
      age of 30 years (range 24-52 years). Nine had blunt trauma while two had suffered
      penetrating injury. Three presented with shock. associated injuries were present
      in nine patients (head, chest, and extremities) while seven had other intra
      abdominal injuries. Only one patient had isolated pancreatic injury. Early serum
      amylase was elevated in six patients. CT abdomen was diagnostic for pancreatic
      injury in seven patients. Two cases were missed by early CT scan (sensitivity of
      78%) while the remaining two patients were taken immediately to the operating
      theater. All patients underwent laparotomy. Five patients were treated by
      drainage alone, four had distal pancreatectomy, abdominal packing was performed
      in one patient and in another gastrocystostomy was carried out. Pancreatic
      fistula occurred in three patients. Median hospital stay was 25 days (range 12
      152 days). Two patients (18%) died. CONCLUSIONS: Blunt trauma is the main cause
      of pancreatic injury in our country. Early CT scan may miss pancreatic injury in
      almost a quarter of the patients. Thin sliced CT scan, with special views in a
      dedicated abdominal pancreatic study, is recommended. A high index of clinical
      suspicion, depending on the mechanism of injury, is important for diagnosis of
      pancreatic injury. Mortality is mainly attributable to other associated injuries
      so simple procedures should initially be adopted for pancreatic injury,
      especially in haemodynamically unstable patients.

PMID- 18812275
TI  - The role of adrenal scintigraphy in the preoperative management of primary
      aldosteronism.
AB  - BACKGROUND AND AIMS: Differentiation between the two major subgroups of primary
      aldosteronism, bilateral hyperplasia and aldosterone producing adenoma is
      essential since therapy in the former is medical and in the latter surgical. The
      aim of the present study was to evaluate the clinical utility of adrenocortical
      scintigraphy in the management of primary aldosteronism. MATERIAL AND METHODS:
      [131I] norcholesterol (NP-59) scintigraphy with dexamethasone suppression for
      subclassification and lateralization of primary aldosteronism was evaluated in 49
      patients with long-term follow-up after diagnosis and treatment. RESULTS: Thirty
      three patients with the diagnosis of aldosterone producing adenoma were operated
      with adrenalectomy. Preoperative scintigraphy showed lateralized isotope uptake
      in 27/33 patients while 6 showed no uptake. Twenty-two were cured and three
      significantly improved. Thus, in 25/33 (76%), scintigraphy showed the correct
      side as the patients benefited of surgery. Two patients did not improve. Fourteen
      patients with a probable diagnosis of bilateral hyperplasia had normal
      scintigraphies. CONCLUSIONS: In the present retrospective study we found limited
      sensitivity of NP-59 scintigraphy. However, when a lateralized scintigraphic
      uptake is achieved it has a high accuracy. Scintigraphy may be used as an adjunct
      in cases where adrenal venous sampling is inconclusive.

PMID- 18812276
TI  - An evaluation of mitral valve procedures using the European system for cardiac
      operative risk evaluation.
AB  - BACKGROUND AND AIMS: This study was undertaken in order to evaluate the
      usefulness of the Euroscore in the choice and outcome of mitral valve procedures
      undertaken at the Helsinki University Central Hospital. MATERIAL AND METHODS:
      Data from 378 patients was collected. predicted mortalities were calculated for
      all patients using the European System for Cardiac Operative Risk Evaluation and
      different mitral valve procedures were compared with 30-day mortality, length of
      hospital care and rate of post-operative complications. RESULTS: The mortality
      rate in the mitral valve repair (MVP) group decreased gradually from 5.9% (in
      1999) to 2.2% (2003). The variation of annual mortality was higher in the mitral
      valve replacement (MVR) group. The predicted mortality given by Euroscore
      increased over the years in both groups. The mortality in the MVR group was
      nearly four times higher than in the MVP group. the length of both intensive and
      overall hospital stay decreased in patients with MVP procedures. Post-operative
      survival was 89% in the MVP patients and 74% in mvr patients after three years.
      DISCUSSION: The results of mitral valve operations have improved. This is
      observed as decreased mortality rates and lengths of hospital care in the MVP
      group, although the predicted mortality rate was increased.

PMID- 18812277
TI  - Haemodynamics and acid-base equilibrium after cardiac surgery: comparison of
      rapidly degradable hydroxyethyl starch solutions and albumin.
AB  - BACKGROUND: Stable haemodynamics is often achieved by administration of colloids
      after cardiac surgery. We conducted a prospective, randomized, open-label study
      comparing haemodynamics and acid-base equilibrium after infusion of two rapidly
      degradable hydroxyethyl starch (HES) solutions or human albumin (HA) to cardiac
      surgical patients. MATERIALS AND METHODS: 45 patients received a predetermined
      fixed dose of 15 ml kg(-1) of either 6% HES (mW 130 kDa, n = 15), 6% HES (MW 200
      kDa, n = 15) or 4% HA (MW 69 kDa, n = 15) after on-pump cardiac surgery. RESULTS:
      Left ventricular filling pressures assessed using pulmonary artery catheter
      responded similarly in all groups. mean (SD) cardiac index was higher in HES130
      [3.5 l min(-1) m(-2) (0.7) ] and HES200 [3.5 l min(-1) m(-2) (0.5)] than in HA
      [2.8 l min(-1) m(-2) (0.6)] group after completion of infusion (P = 0.002) but no
      differences were detected at 2 and 18 hours. Oxygen delivery increased in both
      HES groups but not in HA group. After cessation of infusion base excess was the
      most negative in Ha group. At 2 hours mean (SD) base excess was higher in HES130
      [0 (1.32)] than in HES200 [-1.32 (2.27) ] and HA [-2.3 (1.3)] group (P = 0.002,
      between the groups). CONCLUSIONS: We conclude that the effect of albumin on
      cardiac performance is inferior than that of HES130 or HES200 in early
      postoperative phase after cardiac surgery. HES130 induces no alterations in acid
      base equilibrium whereas a negative base excess was observed after HA infusion.

PMID- 18812278
TI  - The impact of proximal femur geometry on fracture type--a comparison between
      cervical and trochanteric fractures with two parameters.
AB  - INTRODUCTION: Only a few studies have tested the ability of proximal femur
      geometry parameters to discriminate between cervical hip fractures and those of
      the trochanter. The main objective of this study was to evaluate the geometrical
      differences between these two fracture types by measuring the neck shaft angle
      (NSA) and the femoral neck axis length (FNAL). We also compared the distributions
      of these parameters and the distributions of fracture type by gender. MATERIAL
      AND METHODS: A retrospective analysis was made in a population-based material of
      428 hip fractures collected during a two-year period from 1999 to 2000 (323 women
      and 105 men aged 65 years or older). NSA and FNAL were manually measured from
      pelvic radiographs. RESULTS: No significant differences in NSA or FNAL were found
      between cervical and trochanteric hip fractures in women or in men. Men had
      significantly higher NSA and FNAL than women. Age was not related to these
      geometrical parameters. The distributions by fracture type were similar in both
      genders. CONCLUSIONS: The different pathogenesis of cervical and trochanteric hip
      fractures cannot be explained by NSA or FNAL. A standardized measurement setup is
      needed when evaluating the role of hip geometry in fracture patients.

PMID- 18812279
TI  - The increasing incidence and difference in sex distribution of Achilles tendon
      rupture in Finland in 1987-1999.
AB  - BACKGROUND AND AIMS: There have been reports about the increasing number of
      Achilles tendon ruptures. The most of the reports are based on records in a few
      hospitals only. We wanted to verify the increasing trend by investigating the
      epidemiology of Achilles tendon rupture in a very large population. MATERIAL AND
      METHODS: The retrospective data was collected from 1987 to 1999 in Finnish
      National Hospital Discharge Register. The study includes 7 375 tendon rupture
      patients. We recorded their age, gender, home district and the date of admission
      in a hospital. RESULTS: The incidence of operatively treated Achilles tendon
      rupture was 11.2/105. The number of the patients was increasing particularly in
      the old age-groups. The change during the study period was statistically
      significant (p = 0.015). The females with a tendon rupture were on average 2-3
      years older than men (p < 0.01). The urban areas around the capital city had a
      higher occurrence of tendon ruptures than the rural areas (p < 0.05). CONCLUSION:
      The number of Achilles tendon ruptures is increasing, but the reasons for this
      remain unknown. The geographical variations in rupture rate might indicate the
      role of the urban life-style as a risk factor. One reason for the differences
      between the men and the women might be the different level of the sport
      activities, especially ball-games.

PMID- 18812280
TI  - [Determination of total polyphenol content in food with the flow-injection
      method].
AB  - This paper describes an optimised flow-injection method for the determination of
      total polyphenol in food based on the Folin-Ciocalteau reaction in 0.5 mol L(-1)
      NaOH. The method allows different types of samples to be analysed automatically
      at a rate of 55 samples per hour by using gallic acid as standard. By applying
      the proposed method to real samples (white and red wines, green, Indian, lime
      tree, mentha and chamomile teas, and blackberry and cherry juices), their total
      polyphenol indices were determined with a higher reproducibility than obtained by
      earlier methods, whatever the dilution used. This method is highly tolerant
      towards the most common interferences (SO2, reducing sugars, and ascorbic acid)
      associated with the batch method. The results obtained by the proposed method
      relatively agree with those obtained using the referent Folin-Ciocalteau method.

PMID- 18812281
TI  - [First midwives in the town of Bjelovar, Croatia 1756-1856].
AB  - The first trained (certified) midwives came to the newly founded town of
      Bjelovar, a strong military centre of Vojna Krajina (Croatian province bordering
      Ottoman Empire), at the beginning of the 1750s, along with army physicians,
      surgeons, and pharmacists. Most were of German origin. The archival material
      investigated for the period 1756-1856 speaks of 23 certified midwives, of whom 14
      were regimental and nine municipal. This period was characterised by high
      neonatal and maternal mortality rates and criminal abortions. Within the scope of
      the domiciliary midwifery model that included care for pregnant women, parturient
      women, neonates, and infants, midwives used to act as godmothers to newborns at
      risk, in periculo, or to healthy newborns. Although Bjelovar had professional
      midwifery service, the practice of unassisted childbirths continued in the town
      surroundings. Unlike other inland and coastal (Dalmatian) towns of the time,
      Bjelovar has had a continuous tradition of training midwives and maternal health
      care since the 1750s.

PMID- 18812282
TI  - Sebastian syndrome with abnormal platelet response to ristocetin.
AB  - BACKGROUND: Sebastian syndrome is characterized by enlarged platelets and Dohle
      like body leukocyte inclusions. This syndrome is an MYH-9-related disease, a
      group that also includes May-Hegglin anomaly and Fechtner syndrome. The
      differential diagnosis of the MYH-9 diseases requires ultrastructural studies.
      Certain in vitro aggregation responses may be abnormal in these conditions.
      OBSERVATIONS: A 6-month-old boy presented with macrothrombocytopenia but no overt
      bleeding tendency. Giant platelets and Dohle-like body leukocyte inclusions were
      present in blood smears from both the patient and his mother. Electron microscopy
      confirmed ultrastructural features consistent with Sebastian syndrome. Platelet
      aggregation studies were normal except for an impaired response to the agonist
      ristocetin. CONCLUSIONS: In this patient peripheral blood analyses and platelet
      aggregation studies revealed disease features shared with the Bernard-Soulier
      syndrome, but this syndrome was excluded by cellsurface glycoprotein analysis.

PMID- 18812283
TI  - Stability tests for hematological parameters in antidoping analyses.
AB  - The purpose of this study was to evaluate the influences of delayed sample
      analysis on the stability of erythrocyte parameters and reticulocyte parameters
      for antidoping tests performed on the ADVIA120 system. We analyzed erythrocyte
      count, hemoglobin, hematocrit, mean cell volume, percentage of hypochromic
      erythrocytes, percentage of macrocytes, absolute reticulocyte count, percentage
      of reticulocytes, mean cell volume of reticulocytes, cell hemoglobin of
      reticulocytes, percentage of high-fluorescent reticulocytes, and OFF-Score during
      a 48-hour storage period at 4 degrees C or 21 degrees C. Data analysis was
      performed by fitting linear or nonlinear mixed-effects models. We then modeled
      appropriate trends and tested the curve parameters' interaction with the ambient
      temperature. We observed that chilling of samples to 4 degrees C generally proved
      more advantageous than storage at room temperature. Sufficient stability during
      48-hour intervals was demonstrated for erythrocyte count, hemoglobin, percentage
      of reticulocytes, absolute reticulocyte count, cell hemoglobin of reticulocytes,
      percentage of hypochromic erythrocytes, percentage of high-fluorescent
      reticulocytes, and OFF-Score. We concluded that for the establishment of
      individual blood profiles the corresponding samples should be transported and
      stored at 4 degrees C. Analysis should be performed not later than 48 hours after
      sampling.

PMID- 18812284
TI  - Compound heterozygosity for hemoglobin C and hemoglobin Korle-Bu.
AB  - We describe a case of compound heterozygosity for hemoglobin C (beta6 Glu-->Lys)
      and hemoglobin Korle-Bu (beta73 Asp-->Asn). To our knowledge, this is the third
      case report of this unusual hemoglobin genotype, and the first to integrate data
      from cation exchange high-performance liquid chromatography, hemoglobin
      electrophoresis, and beta-globin gene sequencing. The principal hematological
      finding in our case was microcytosis without significant anemia. The previous
      case reports of this hemoglobinopathy also describe microcytosis, with varying
      degrees of hemolytic anemia. Given the relative gene frequencies of hemoglobins C
      and Korle-Bu, the occurrence of this compound-heterozygous genotype should be
      anticipated in people of African ancestry.

PMID- 18812285
TI  - Effect of Reynolds number and flow division on patterns of haemodynamic wall
      shear stress near branch points in the descending thoracic aorta.
AB  - Atherosclerotic lesions are non-uniformly distributed at arterial bends and
      branch sites, suggesting an important role for haemodynamic factors, particularly
      wall shear stress (WSS), in their development. The pattern of lesions at aortic
      branch sites depends on age and species. Using computational flow simulations in
      an idealized model of an intercostal artery emerging perpendicularly from the
      thoracic aorta, we studied the effects of Reynolds number and flow division under
      steady conditions. Patterns of flow and WSS were strikingly dependent on these
      haemodynamic parameters. With increasing Reynolds number, WSS, normalized by the
      fully developed aortic value, was lowered at the sides of the ostium and
      increased upstream and downstream of it. Increasing flow into the side branch
      exacerbated these patterns and gave rise to a reversing flow region downstream of
      the ostium. Incorporation of more realistic geometric features had only minor
      effects and patterns of mean WSS under pulsatile conditions were similar to the
      steady flow results. Aspects of the observed WSS patterns correlate with, and may
      explain, some but not all of the lesion patterns in human, rabbit and mouse
      aortas.

PMID- 18812287
TI  - Lake warming favours small-sized planktonic diatom species.
AB  - Diatoms contribute to a substantial portion of primary production in the oceans
      and many lakes. Owing to their relatively heavy cell walls and high nutrient
      requirements, planktonic diatoms are expected to decrease with climate warming
      because of reduced nutrient redistribution and increasing sinking velocities.
      Using a historical dataset, this study shows that diatoms were able to maintain
      their biovolume with increasing stratification in Lake Tahoe over the last
      decades; however, the diatom community structure changed. Increased
      stratification and reduced nitrogen to phosphorus ratios selected for small
      celled diatoms, particularly within the Cyclotella genus. An empirical model
      showed that a shift in phytoplankton species composition and cell size was
      consistent within different depth strata, indicating that altered nutrient
      concentrations were not responsible for the change. The increase in small-celled
      species was sufficient to decrease the average diatom size and thus sinking
      velocity, which strongly influences energy transfer through the food web and
      carbon cycling. Our results show that within the diverse group of diatoms, small
      sized species with a high surface area to volume ratio were able to adapt to a
      decrease in mixing intensity, supporting the hypotheses that abiotic drivers
      affect the size structure of planktonic communities and that warmer climate
      favours small-sized diatom cells.

PMID- 18812288
TI  - Evolutionary dynamics of collective action in N-person stag hunt dilemmas.
AB  - In the animal world, collective action to shelter, protect and nourish requires
      the cooperation of group members. Among humans, many situations require the
      cooperation of more than two individuals simultaneously. Most of the relevant
      literature has focused on an extreme case, the N-person Prisoner's Dilemma. Here
      we introduce a model in which a threshold less than the total group is required
      to produce benefits, with increasing participation leading to increasing
      productivity. This model constitutes a generalization of the two-person stag hunt
      game to an N-person game. Both finite and infinite population models are studied.
      In infinite populations this leads to a rich dynamics that admits multiple
      equilibria. Scenarios of defector dominance, pure coordination or coexistence may
      arise simultaneously. On the other hand, whenever one takes into account that
      populations are finite and when their size is of the same order of magnitude as
      the group size, the evolutionary dynamics is profoundly affected: it may
      ultimately invert the direction of natural selection, compared with the infinite
      population limit.

PMID- 18812289
TI  - Lifespan, lifetime reproductive performance and paternity loss of within-pair and
      extra-pair offspring in the coal tit Periparus ater.
AB  - The hypothesis that females of socially monogamous species obtain indirect
      benefits (good or compatible genes) from extra-pair mating behaviour has received
      enormous attention but much less generally accepted support. Here we ask whether
      selection for adult survival and fecundity or sexual selection contribute to
      indirect selection of the extra-pair mating behaviour in socially monogamous coal
      tits (Periparus ater). We tracked locally recruited individuals with known
      paternity status through their lives predicting that the extra-pair offspring
      (EPO) would outperform the within-pair offspring (WPO). No differences between
      the WPO and EPO recruits were detected in lifespan or age of first reproduction.
      However, the male WPO had a higher lifetime number of broods and higher lifetime
      number of social offspring compared with male EPO recruits, while no such
      differences were evident for female recruits. Male EPO recruits did not
      compensate for their lower social reproductive success by higher fertilization
      success within their social pair bonds. Thus, our results do not support the idea
      that enhanced adult survival, fecundity or within-pair fertilization success are
      manifestations of the genetic benefits of extra-pair matings. But we emphasize
      that a crucial fitness component, the extra-pair fertilization success of male
      recruits, has yet

PMID- 18812290
TI  - Inheritance and diversification of symbiotic trichonymphid flagellates from a
      common ancestor of termites and the cockroach Cryptocercus.
AB  - Cryptocercus cockroaches and lower termites harbour obligate, diverse and unique
      symbiotic cellulolytic flagellates in their hindgut that are considered critical
      in the development of social behaviour in their hosts. However, there has been
      controversy concerning the origin of these symbiotic flagellates. Here, molecular
      sequences encoding small subunit rRNA and glyceraldehyde-3-phosphate
      dehydrogenase were identified in the symbiotic flagellates of the order
      Trichonymphida (phylum Parabasalia) in the gut of Cryptocercus punctulatus and
      compared phylogenetically to the corresponding species in termites. In each of
      the monophyletic lineages that represent family-level groups in Trichonymphida,
      the symbionts of Cryptocercus were robustly sister to those of termites. Together
      with the recent evidence for the sister-group relationship of the host insects,
      this first comprehensive study comparing symbiont molecular phylogeny strongly
      suggests that a set of symbiotic flagellates representative of extant diversity
      was already established in an ancestor common to Cryptocercus and termites, was
      vertically transmitted to their offspring, and subsequently became diversified to
      distinct levels, depending on both the host and the symbiont lineages.

PMID- 18812291
TI  - Size-structured risk assessments govern Daphnia migration.
AB  - One of the more fascinating phenomena in nature is animal mass migrations and in
      oceans and freshwaters, diel variations in depth distribution of zooplankton are
      a phenomenon that has intrigued scientists for more than a century. In our study,
      we show that zooplankton are able to assess the threat level of ultraviolet
      radiation and adjust their depth distribution to this level at a very fine tuned
      scale. Moreover, predation risk induces a size-structured depth separation, such
      that small individuals, which we show are less vulnerable to predation than
      larger, make a risk assessment and continue feeding in surface waters during day,
      offering a competitive release from down-migrating larger animals. Hence, we
      mechanistically show that such simple organisms as invertebrate zooplankton are
      able to make individual, size-specific decisions regarding how to compromise
      between threats from both predators and UV radiation, and adjust their diel
      migratory patterns accordingly.

PMID- 18812292
TI  - Constraining free riding in public goods games: designated solitary punishers can
      sustain human cooperation.
AB  - Much of human cooperation remains an evolutionary riddle. Unlike other animals,
      people frequently cooperate with non-relatives in large groups. Evolutionary
      models of large-scale cooperation require not just incentives for cooperation,
      but also a credible disincentive for free riding. Various theoretical solutions
      have been proposed and experimentally explored, including reputation monitoring
      and diffuse punishment. Here, we empirically examine an alternative theoretical
      proposal: responsibility for punishment can be borne by one specific individual.
      This experiment shows that allowing a single individual to punish increases
      cooperation to the same level as allowing each group member to punish and results
      in greater group profits. These results suggest a potential key function of
      leadership in human groups and provides further evidence supporting that humans
      will readily and knowingly behave altruistically.

PMID- 18812293
TI  - High dispersal potential has maintained long-term population stability in the
      North Atlantic copepod Calanus finmarchicus.
AB  - The cool-water copepod Calanus finmarchicus is a key species in North Atlantic
      marine ecosystems since it represents an important food resource for the
      developmental stages of several fish of major economic value. Over the last 40
      years, however, data from the Continuous Plankton Recorder survey have
      highlighted a 70 per cent reduction in C. finmarchicus biomass, coupled with a
      gradual northward shift in the species's distribution, which have both been
      linked with climate change. To determine the potential for C. finmarchicus to
      track changes in habitat availability and maintain stable effective population
      sizes, we have assessed levels of gene flow and dispersal in current populations,
      as well as using a coalescent approach together with palaeodistribution modelling
      to elucidate the historical population demography of the species over previous
      changes in Earth's climate. Our findings indicate high levels of dispersal and a
      constant effective population size over the period 359,000-566,000 BP and suggest
      that C. finmarchicus possesses the capacity to track changes in available
      habitat, a feature that may be of crucial importance to the species's ability to
      cope with the current period of global climate change.

PMID- 18812294
TI  - Incomplete reproductive isolation following host shift in brood parasitic
      indigobirds.
AB  - Behavioural and molecular studies suggest that brood parasitic indigobirds (Vidua
      spp.) rapidly diversified through a process of speciation by host shift. However,
      behavioural imprinting on host song, the key mechanism promoting speciation in
      this system, may also lead to hybridization and gene flow among established
      indigobird species when and if female indigobirds parasitize hosts already
      associated with other indigobird species. It is therefore not clear to what
      extent the low level of genetic differentiation among indigobird species is due
      to recent common ancestry versus ongoing gene flow. We tested for reproductive
      isolation among three indigobird species in Cameroon, one of which comprises two
      morphologically indistinguishable host races. Mimicry of host songs corresponded
      with plumage colour in 184 male indigobirds, suggesting that females rarely
      parasitize the host of another indigobird species. Paternity analyses, however,
      suggest that imperfect specificity in host and/or mate choice allows for
      continuing gene flow between recently formed host races of the Cameroon
      Indigobird Vidua camerunensis; while 63 pairs of close relatives were associated
      with the same host, two strongly supported father-son pairs included males
      mimicking the songs of the two different hosts of V. camerunensis. Thus, complete
      reproductive isolation is not necessarily an automatic consequence of host
      shifts, a result that suggests an important role for natural and/or sexual
      selection in indigobird speciation.

PMID- 18812295
TI  - On the acceleration of ultra-high-energy cosmic rays.
AB  - Ultra-high-energy cosmic rays (UHECRs) hit the Earth's atmosphere with energies
      exceeding 10(18)eV. This is the same energy as carried by a tennis ball moving at
      100 km h-1, but concentrated on a subatomic particle. UHECRs are so rare (the
      flux of particles with E>10(20)eV is 0.5 km -2 per century) that only a few such
      particles have been detected over the past 50 years. Recently, the HiRes and
      Auger experiments have reported the discovery of a high-energy cut-off in the
      UHECR spectrum, and Auger has found an apparent clustering of the highest energy
      events towards nearby active galactic nuclei. Consensus is building that the
      highest energy particles are accelerated within the radio-bright lobes of these
      objects, but it remains unclear how this actually happens, and whether the cut
      off is due to propagation effects or reflects an intrinsically physical
      limitation of the acceleration process. The low event statistics presently allows
      for many different plausible models; nevertheless observations are beginning to
      impose strong constraints on them. These observations have also motivated
      suggestions that new physics may be implicated. We present a review of the key
      theoretical and observational issues related to the processes of propagation and
      acceleration of UHECRs and proposed solutions.

PMID- 18812296
TI  - Introduction. Progress in astronomy: from gravitational waves to space weather.
AB  - This brief paper introduces and reviews the 'visions of the future' articles
      prepared by leading young scientists throughout the world for the first of two
      Christmas 2008 Triennial issues of Phil. Trans. R. Soc. A, devoted, respectively,
      to astronomy and Earth science. Contributions in astronomy include the very
      topical gamma-ray bursts, new ideas on stellar collapse and the unusual
      atmospheres of synchronized planets orbiting nearby stars.

PMID- 18812297
TI  - Creating synthetic universes in a computer.
AB  - Cosmologists regularly generate synthetic universes of galaxies using computer
      simulations. Such catalogues have an essential role to play in the analysis and
      exploitation of current and forthcoming galaxy surveys. I review the different
      ways in which synthetic or 'mock' catalogues are produced and discuss the
      different physical processes that the models attempt to follow, explaining why it
      is important to be as realistic as possible when trying to forge the Universe.

PMID- 18812298
TI  - Atmospheric dynamics of tidally synchronized extrasolar planets.
AB  - Tidally synchronized planets present a new opportunity for enriching our
      understanding of atmospheric dynamics on planets. Subject to an unusual forcing
      arrangement (steady irradiation on the same side of the planet throughout its
      orbit), the dynamics on these planets may be unlike that on any of the Solar
      System planets. Characterizing the flow pattern and temperature distribution on
      the extrasolar planets is necessary for reliable interpretation of data currently
      being collected, as well as for guiding future observations. In this paper,
      several fundamental concepts from atmospheric dynamics, likely to be central for
      characterization, are discussed. Theoretical issues that need to be addressed in
      the near future are also highlighted.

PMID- 18812299
TI  - Magnetic fields in astrophysical objects.
AB  - Magnetic fields are known to reside in many astrophysical objects and are now
      believed to be crucially important for the creation of phenomena on a wide
      variety of scales. However, the role of the magnetic field in the bodies that we
      observe has not always been clear. In certain situations, the importance of a
      magnetic field has been overlooked on the grounds that the large-scale magnetic
      field was believed to be too weak to play an important role in the dynamics. In
      this article I discuss some of the recent developments concerning magnetic fields
      in stars, planets and accretion discs. I choose to emphasize some of the
      situations where it has been suggested that weak magnetic fields may play a more
      significant role than previously thought. At the end of the article, I list some
      of the questions to be answered in the future.

PMID- 18812300
TI  - The black hole symphony: probing new physics using gravitational waves.
AB  - The next decade will very likely see the birth of a new field of astronomy as we
      become able to directly detect gravitational waves (GWs) for the first time. The
      existence of GWs is one of the key predictions of Einstein's theory of general
      relativity, but they have eluded direct detection for the last century. This will
      change thanks to a new generation of laser interferometers that are already in
      operation or which are planned for the near future. GW observations will allow us
      to probe some of the most exotic and energetic events in the Universe, the
      mergers of black holes. We will obtain information about the systems to a
      precision unprecedented in astronomy, and this will revolutionize our
      understanding of compact astrophysical systems. Moreover, if any of the
      assumptions of relativity theory are incorrect, this will lead to subtle, but
      potentially detectable, differences in the emitted GWs. Our observations will
      thus provide very precise verifications of the theory in an as yet untested
      regime. In this paper, I will discuss what GW observations could tell us about
      known and (potentially) unknown physics.

PMID- 18812301
TI  - Wonderful Mira.
AB  - Since being named 'wonderful' in the seventeenth century for its peculiar
      brightness variability, Mira A has been the subject of extensive research and
      become the prototype for a whole class of 'Mira' variable stars. The primary star
      in a binary system, Mira A is reaching the end of its life and currently
      undergoing an extended period of enhanced mass loss. Recent observations have
      revealed a surrounding arc-like structure and a stream of material stretching 12
      light years away in opposition to the arc. In this article, I review recent
      modelling of this cometary appearance as a bow shock with an accompanying tail of
      material ram pressure stripped from the head of the bow shock, place Mira in an
      evolutionary context, predict its future with reference to the similar star R Hya
      and planetary nebula Sh 2-188, and speculate some avenues of research both on
      Mira itself and on other 'Mira-like' stars with bow shocks and tails. I also
      discuss the implications of this discovery for our own star, the Sun.

PMID- 18812302
TI  - The science of space weather.
AB  - The basic physics underpinning space weather is reviewed, beginning with a brief
      overview of the main causes of variability in the near-Earth space environment.
      Although many plasma phenomena contribute to space weather, one of the most
      important is magnetic reconnection, and recent cutting edge research in this
      field is reviewed. We then place this research in context by discussing a number
      of specific types of space weather in more detail. As society inexorably
      increases its dependence on space, the necessity of predicting and mitigating
      space weather will become ever more acute. This requires a deep understanding of
      the complexities inherent in the plasmas that fill space and has prompted the
      development of a new generation of scientific space missions at the international
      level.

PMID- 18812303
TI  - Massive stars in their death throes.
AB  - The study of the stars that explode as supernovae used to be a forensic study,
      working backwards from the remnants of the star. This changed in 1987 when the
      first progenitor star was identified in pre-explosion images. Currently, there
      are eight detected progenitors with another 21 non-detections, for which only a
      limit on the pre-explosion luminosity can be placed. This new avenue of supernova
      research has led to many interesting conclusions, most importantly that the
      progenitors of the most common supernovae, type IIP, are red supergiants, as
      theory has long predicted. However, no progenitors have been detected thus far
      for the hydrogen-free type Ib/c supernovae, which, given the expected
      progenitors, is an unlikely result. Also, observations have begun to show
      evidence that luminous blue variables, which are among the most massive stars,
      may directly explode as supernovae. These results contradict the current stellar
      evolution theory. This suggests that we may need to update our understanding.

PMID- 18812304
TI  - Magnetic fields in the solar photosphere.
AB  - Recent high-resolution observations of the surface of the Sun have revealed the
      fine structure of a vast array of complex photospheric magnetic features.
      Observations of these magnetic field structures have already greatly enhanced our
      theoretical understanding of the interactions between magnetic fields and
      turbulent convection, and future photospheric observations will inevitably
      present new theoretical challenges. In this review, I discuss recent progress
      that has been made in the modelling of photospheric magnetic fields. In
      particular, I focus upon the complex field structures that are observed within
      the umbrae and the penumbrae of sunspots. On a much smaller scale, I also discuss
      models of the highly localized magnetic field structures that are observed in
      less magnetically active regions of the photosphere. As the spatial resolution of
      telescopes has improved over the last few years, it has now become possible to
      observe these features in detail, and theoretical models can now describe much of
      this behaviour. In the last section of this review, I discuss some of the
      remaining unanswered questions.

PMID- 18812305
TI  - On the origin of gamma-ray bursts.
AB  - Gamma-ray bursts are the most energetic explosions in the Universe, occurring at
      cosmological distances. The initial phase of the emission from these bursts is
      predominantly of gamma rays and stems from a highly relativistic outflow. The
      nature of this emission is still under debate. Here, I present the interpretation
      that the peak in the photon spectrum can be attributed to the black-body emission
      of the photosphere of the outflow, having a temperature of approximately 109K. An
      additional non-thermal spectral component can be attributed to additional
      dissipation of the kinetic energy in the outflow. This two-component model can be
      well fitted to most instantaneous spectra. Interestingly, the thermal component
      exhibits a recurring behaviour over emission pulse structures. Both the
      temperature and the energy flux vary as broken power laws. During the pre-break
      phase, the temperature is approximately constant while the energy flux rises.
      Furthermore, the ratio of the observed thermal flux to the emergent flux
      increases as a power law over the whole pulse. It is argued that these
      observations hold the key to our understanding of the prompt emission and the
      properties of the site from which it emanates.

PMID- 18812306
TI  - The Swift satellite lives up to its name, revealing cosmic explosions as they
      happen.
AB  - Gamma-ray bursts are the most powerful objects in the Universe. Discovered in the
      1960s as brief flashes of gamma radiation, we now know that they emit across the
      entire electromagnetic spectrum, are located in distant galaxies and comprise two
      distinct populations, one of which may originate in the deaths of massive stars.
      The launch of the Swift satellite in 2004 brought a flurry of new discoveries,
      advancing our understanding of these sources and the galaxies that host them. I
      highlight a number of important results from the Swift era thus far.

PMID- 18812307
TI  - Seasonal variation in sonic muscles in the fawn cusk-eel Lepophidium profundorum.
AB  - The fawn cusk-eel Lepophidium profundorum (Ophidiidae) has an unusual sound
      producing system with sexually dimorphic sets of antagonistic muscles. Outside
      the mating season, the dorsal and ventral muscles are well developed and larger
      in males than in females, but the tiny intermediate muscles are smaller,
      suggesting a minor role, if any, in male advertisement call production. We
      examined summer individuals with more developed gonads and find a fourfold
      hypertrophy of the intermediate but not the other muscles. This result suggests
      androgen dependence and an important role in sound production for the
      intermediate muscle. Even though both sexes gain weight in the summer, the
      ventral and dorsal muscles in females lose weight, suggesting that sound
      production is less important in females and that muscle mass may be used to
      support egg growth.

PMID- 18812308
TI  - Potential confounds to an assay of cross-generational fitness benefits of mating
      and male seminal fluid.

PMID- 18812309
TI  - Helping behaviour and regard for others in capuchin monkeys (Cebus apella).
AB  - Altruism is an evolutionary puzzle. To date, much debate has focused on whether
      helping others without regard to oneself is a uniquely human behaviour, with a
      variety of empirical studies demonstrating a lack of altruistic behaviour in
      chimpanzees even when the demands of behaving altruistically seem minimal. By
      contrast, a recent experiment has demonstrated that chimpanzees will help a human
      experimenter to obtain an out-of-reach object, irrespective of whether or not
      they are offered a reward for doing so, suggesting that the cognitions underlying
      altruistic behaviour may be highly sensitive to situational demands. Here, we
      examine the cognitive demands of other-regarding behaviour by testing the
      conditions under which primates more distantly related to humans--capuchin
      monkeys--help an experimenter to obtain an out-of-reach object. Like chimpanzees,
      capuchin monkeys helped human experimenters even in the absence of a reward, but
      capuchins systematically failed to take into account the perspective of others
      when they stood to obtain food for themselves. These results suggest an important
      role for perspective taking and inhibition in altruistic behaviour and seem to
      reflect a significant evolutionary development in the roots of altruism, and
      specifically in other-regarding behaviour, between the divergence of New World
      monkeys and apes.

PMID- 18812311
TI  - The first 50Myr of dinosaur evolution: macroevolutionary pattern and
      morphological disparity.
AB  - The evolutionary radiation of dinosaurs in the Late Triassic and Early Jurassic
      was a pivotal event in the Earth's history but is poorly understood, as previous
      studies have focused on vague driving mechanisms and have not untangled different
      macroevolutionary components (origination, diversity, abundance and disparity).
      We calculate the morphological disparity (morphospace occupation) of dinosaurs
      throughout the Late Triassic and Early Jurassic and present new measures of
      taxonomic diversity. Crurotarsan archosaurs, the primary dinosaur 'competitors',
      were significantly more disparate than dinosaurs throughout the Triassic, but
      underwent a devastating extinction at the Triassic-Jurassic boundary. However,
      dinosaur disparity showed only a slight non-significant increase after this
      event, arguing against the hypothesis of ecological release-driven morphospace
      expansion in the Early Jurassic. Instead, the main jump in dinosaur disparity
      occurred between the Carnian and Norian stages of the Triassic. Conversely,
      dinosaur diversity shows a steady increase over this time, and measures of
      diversification and faunal abundance indicate that the Early Jurassic was a key
      episode in dinosaur evolution. Thus, different aspects of the dinosaur radiation
      (diversity, disparity and abundance) were decoupled, and the overall
      macroevolutionary pattern of the first 50Myr of dinosaur evolution is more
      complex than often considered.

PMID- 18812312
TI  - Examining the medical blogosphere: an online survey of medical bloggers.
AB  - BACKGROUND: Blogs are the major contributors to the large increase of new
      websites created each year. Most blogs allow readers to leave comments and, in
      this way, generate both conversation and encourage collaboration. Despite their
      popularity, however, little is known about blogs or their creators. OBJECTIVES:
      To contribute to a better understanding of the medical blogosphere by
      investigating the characteristics of medical bloggers and their blogs, including
      bloggers' Internet and blogging habits, their motivations for blogging, and
      whether or not they follow practices associated with journalism. METHODS: We
      approached 197 medical bloggers of English-language medical blogs which provided
      direct contact information, with posts published within the past month. The
      survey included 37 items designed to evaluate data about Internet and blogging
      habits, blog characteristics, blogging motivations, and, finally, the demographic
      data of bloggers. Pearson's Chi-Square test was used to assess the significance
      of an association between 2 categorical variables. Spearman's rank correlation
      coefficient was utilized to reveal the relationship between participants' ages,
      as well as the number of maintained blogs, and their motivation for blogging. The
      Mann-Whitney U test was employed to reveal relationships between practices
      associated with journalism and participants' characteristics like gender and
      pseudonym use. RESULTS: A total of 80 (42%) of 197 eligible participants
      responded. The majority of responding bloggers were white (75%), highly educated
      (71% with a Masters degree or doctorate), male (59%), residents of the United
      States (72%), between the ages of 30 and 49 (58%), and working in the healthcare
      industry (67%). Most of them were experienced bloggers, with 23% (18/80) blogging
      for 4 or more years, 38% (30/80) for 2 or 3 years, 32% (26/80) for about a year,
      and only 7% (6/80) for 6 months or less. Those who received attention from the
      news media numbered 66% (53/80). When it comes to best practices associated with
      journalism, the participants most frequently reported including links to original
      source of material and spending extra time verifying facts, while rarely seeking
      permission to post copyrighted material. Bloggers who have published a scientific
      paper were more likely to quote other people or media than those who have never
      published such a paper (U= 506.5, n(1)= 41, n(2)= 35, P= .016). Those blogging
      under their real name more often included links to original sources than those
      writing under a pseudonym (U= 446.5, n(1)= 58, n(2)= 19, P= .01). Major
      motivations for blogging were sharing practical knowledge or skills with others,
      influencing the way others think, and expressing oneself creatively. CONCLUSIONS:
      Medical bloggers are highly educated and devoted blog writers, faithful to their
      sources and readers. Sharing practical knowledge and skills, as well as
      influencing the way other people think, were major motivations for blogging among
      our medical bloggers. Medical blogs are frequently picked up by mainstream media;
      thus, blogs are an important vehicle to influence medical and health policy.

PMID- 18812313
TI  - The ALFA (Activity Log Files Aggregation) toolkit: a method for precise
      observation of the consultation.
AB  - BACKGROUND: There is a lack of tools to evaluate and compare Electronic patient
      record (EPR) systems to inform a rational choice or development agenda.
      OBJECTIVE: To develop a tool kit to measure the impact of different EPR system
      features on the consultation. METHODS: We first developed a specification to
      overcome the limitations of existing methods. We divided this into work packages:
      (1) developing a method to display multichannel video of the consultation; (2)
      code and measure activities, including computer use and verbal interactions; (3)
      automate the capture of nonverbal interactions; (4) aggregate multiple
      observations into a single navigable output; and (5) produce an output
      interpretable by software developers. We piloted this method by filming live
      consultations (n = 22) by 4 general practitioners (GPs) using different EPR
      systems. We compared the time taken and variations during coded data entry,
      prescribing, and blood pressure (BP) recording. We used nonparametric tests to
      make statistical comparisons. We contrasted methods of BP recording using Unified
      Modeling Language (UML) sequence diagrams. RESULTS: We found that 4 channels of
      video were optimal. We identified an existing application for manual coding of
      video output. We developed in-house tools for capturing use of keyboard and mouse
      and to time stamp speech. The transcript is then typed within this time stamp.
      Although we managed to capture body language using pattern recognition software,
      we were unable to use this data quantitatively. We loaded these observational
      outputs into our aggregation tool, which allows simultaneous navigation and
      viewing of multiple files. This also creates a single exportable file in XML
      format, which we used to develop UML sequence diagrams. In our pilot, the GP
      using the EMIS LV (Egton Medical Information Systems Limited, Leeds, UK) system
      took the longest time to code data (mean 11.5 s, 95% CI 8.7-14.2). Nonparametric
      comparison of EMIS LV with the other systems showed a significant difference,
      with EMIS PCS (Egton Medical Information Systems Limited, Leeds, UK) (P = .007),
      iSoft Synergy (iSOFT, Banbury, UK) (P = .014), and INPS Vision (INPS, London, UK)
      (P = .006) facilitating faster coding. In contrast, prescribing was fastest with
      EMIS LV (mean 23.7 s, 95% CI 20.5-26.8), but nonparametric comparison showed no
      statistically significant difference. UML sequence diagrams showed that the
      simplest BP recording interface was not the easiest to use, as users spent longer
      navigating or looking up previous blood pressures separately. Complex interfaces
      with free-text boxes left clinicians unsure of what to add. CONCLUSIONS: The ALFA
      method allows the precise observation of the clinical consultation. It enables
      rigorous comparison of core elements of EPR systems. Pilot data suggests its
      capacity to demonstrate differences between systems. Its outputs could provide
      the evidence base for making more objective choices between systems.

PMID- 18812314
TI  - Regulation of dynactin through the differential expression of p150Glued isoforms.
AB  - Cytoplasmic dynein and dynactin interact to drive microtubule-based transport in
      the cell. The p150Glued subunit of dynactin binds to dynein, and directly to
      microtubules. We have identified alternatively spliced isoforms of p150Glued that
      are expressed in a tissue-specific manner and which differ significantly in their
      affinity for microtubules. Live cell assays indicate that these alternatively
      spliced isoforms also differ significantly in their microtubule plus end-tracking
      activity, suggesting a mechanism by which the cell may regulate the dynamic
      localization of dynactin. To test the function of the microtubule-binding domain
      of p150Glued, we used RNAi to deplete the endogenous polypeptide from HeLa cells,
      followed by rescue with constructs encoding either the full-length polypeptide or
      an isoform lacking the microtubule-binding domain. Both constructs fully rescued
      defects in Golgi morphology induced by depletion of p150Glued, indicating that an
      independent microtubule-binding site in dynactin may not be required for dynactin
      mediated trafficking in some mammalian cell types. In neurons, however, a
      mutation within the microtubule-binding domain of p150Glued results in motor
      neuron disease; here we investigate the effects of four other mutations in highly
      conserved domains of the polypeptide (M571T, R785W, R1101K, and T1249I)
      associated in genetic studies with Amyotrophic Lateral Sclerosis. Both
      biochemical and cellular assays reveal that these amino acid substitutions do not
      result in functional differences, suggesting that these sequence changes are
      either allelic variants or contributory risk factors rather than causative for
      motor neuron disease. Together, these studies provide further insight into the
      regulation of dynein-dynactin function in the cell.

PMID- 18812315
TI  - Heparanase stimulation of protease expression implicates it as a master regulator
      of the aggressive tumor phenotype in myeloma.
AB  - High levels of heparanase are an indicator of poor prognosis in myeloma patients,
      and up-regulation of the enzyme enhances tumor growth, angiogenesis, and
      metastasis in animal models. At least part of the impact of heparanase in driving
      the aggressive tumor phenotype is due to its effect on increasing the expression
      and shedding of the heparan sulfate proteoglycan syndecan-1, a molecule known to
      promote myeloma progression. The present work demonstrated that elevation in
      heparanase expression in myeloma cells stimulates sustained ERK phosphorylation
      that in turn drives MMP-9 expression. In addition, urokinase-type plasminogen
      activator (uPA) and uPA receptor expression levels increased, and blocking the
      proteolytic activation of either MMP-9 or uPA inhibited the heparanase-induced
      increase in syndecan-1 shedding. Together these data provide a mechanism for
      heparanase-induced syndecan-1 shedding and, more importantly, demonstrate that
      heparanase activity in myeloma cells can lead to increased levels of proteases
      that are known to play important roles in the aggressive behavior of myeloma
      tumors. This in addition to its other known biological roles, indicates that
      heparanase acts as a master regulator of the aggressive tumor phenotype by up
      regulating protease expression and activity within the tumor microenvironment.

PMID- 18812316
TI  - The third intracellular loop stabilizes the inactive state of the neuropeptide Y1
      receptor.
AB  - Constitutively active G-protein-coupled receptors (GPCRs) can signal even in the
      absence of ligand binding. Most Class I GPCRs are stabilized in the resting
      conformation by intramolecular interactions involving transmembrane domain (TM) 3
      and TM6, particularly at loci 6.30 and 6.34 of TM6. Signaling by Gi/Go-coupled
      receptors such as the Neuropeptide Y1 receptor decreases already low basal
      metabolite levels. Thus, we examined constitutive activity using a biochemical
      assay mediated by a Gi/Gq chimeric protein and a more direct electrophysiological
      assay. Wild-type (WT-Y1) receptors express no measurable, agonist-independent
      activation, while mu-opioid receptors (MOR) and P2Y12 purinoceptors showed clear
      evidence of constitutive activation, especially in the electrophysiological
      assay. Neither point mutations at TM6 (T6.30A or N6.34A) nor substitution of the
      entire TM3 and TM6 regions from the MOR into the Y1 receptor increased basal WT
      Y1 activation. By contrast, chimeric substitution of the third intracellular loop
      (ICL3) generated a constitutively active, Y1-ICL3-MOR chimera. Furthermore, the
      loss of stabilizing interactions from the native ICL3 enhanced the role of
      surrounding residues to permit basal receptor activation; because constitutive
      activity of the Y1-ICL3-MOR chimera was further increased by point mutation at
      locus 6.34, which did not alter WT-Y1 receptor activity. Our results indicate
      that the ICL3 stabilizes the Y1 receptor in the inactive state and confers
      structural properties critical for regulating Y receptor activation and signal
      transduction. These studies reveal the active participation of the ICL3 in the
      stabilization and activation of Class I GPCRs.

PMID- 18812317
TI  - N-Glycosylation of laminin-332 regulates its biological functions. A novel
      function of the bisecting GlcNAc.
AB  - Laminin-332 (Lm332) is a large heterotrimeric glycoprotein that has been
      identified as a scattering factor, a regulator of cancer invasion as well as a
      prominent basement membrane component of the skin. Past studies have identified
      the functional domains of Lm332 and revealed the relationships between its
      activities and the processing of its subunits. However, there is little
      information available concerning the effects of N-glycosylation on Lm332
      activities. In some cancer cells, an increase of beta1,6-GlcNAc catalyzed by N
      acetylglucosaminyltransferase V (GnT-V) is related to the promotion of cancer
      cell motility. By contrast, bisecting GlcNAc catalyzed by N
      acetylglucosaminyltransferase III (GnT-III) suppresses the further processing
      with branching enzymes, such as GnT-V, and the elongation of N-glycans. To
      examine the effects of those N-glycosylations to Lm332 on its activities, we
      purified Lm332s from the conditioned media of GnT-III- and GnT-V-overexpressing
      MKN45 cells. Lectin blotting and mass spectrometry analyses revealed that N
      glycans containing the bisecting GlcNAc and beta1,6-GlcNAc structures were
      strongly expressed on Lm332 purified from GnT-III-overexpressing (GnT-III-Lm332)
      and GnT-V-overexpressing (GnT-V-Lm332) cells, respectively. Interestingly, the
      cell adhesion activity of GnT-III-Lm332 was apparently decreased compared with
      those of control Lm332 and GnT-V-Lm332. In addition, the introduction of
      bisecting GlcNAc to Lm332 resulted in a decrease in its cell scattering and
      migration activities. The weakened activities were most likely derived from the
      impaired alpha3beta1 integrin clustering and resultant focal adhesion formation.
      Taken together, our results clearly demonstrate for the first time that N
      glycosylation may regulate the biological function of Lm332. This finding could
      introduce a new therapeutic strategy for cancer.

PMID- 18812318
TI  - Tracking cell surface GABAB receptors using an alpha-bungarotoxin tag.
AB  - GABA(B) receptors mediate slow synaptic inhibition in the central nervous system
      and are important for synaptic plasticity as well as being implicated in disease.
      Located at pre- and postsynaptic sites, GABA(B) receptors will influence cell
      excitability, but their effectiveness in doing so will be dependent, in part, on
      their trafficking to, and stability on, the cell surface membrane. To examine the
      dynamic behavior of GABA(B) receptors in GIRK cells and neurons, we have devised
      a method that is based on tagging the receptor with the binding site components
      for the neurotoxin, alpha-bungarotoxin. By using the alpha-bungarotoxin binding
      site-tagged GABA(B) R1a subunit (R1a(BBS)), co-expressed with the R2 subunit, we
      can track receptor mobility using the small reporter, alpha-bungarotoxin
      conjugated rhodamine. In this way, the rates of internalization and membrane
      insertion for these receptors could be measured with fixed and live cells. The
      results indicate that GABA(B) receptors rapidly turnover in the cell membrane,
      with the rate of internalization affected by the state of receptor activation.
      The bungarotoxin-based method of receptor-tagging seems ideally suited to follow
      the dynamic regulation of other G-protein-coupled receptors.

PMID- 18812319
TI  - Isolation of hyperactive mutants of mammalian target of rapamycin.
AB  - The mammalian target of rapamycin (mTOR) is a Ser/Thr kinase that plays essential
      roles in the regulation of a wide array of growth-related processes such as
      protein synthesis, cell sizing, and autophagy. mTOR forms two functionally
      distinct complexes, termed the mTOR complex 1 (mTORC1) and 2 (mTORC2); only the
      former of which is inhibited by rapamycin. Based on the similarity between the
      cellular responses caused by rapamycin treatment and by nutrient starvation, it
      has been widely accepted that modulation in the mTORC1 activity in response to
      nutrient status directs these cellular responses, although direct evidence has
      been scarce. Here we report isolation of hyperactive mutants of mTOR. The
      isolated mTOR mutants exhibited enhanced kinase activity in vitro and rendered
      cells refractory to the dephosphorylation of the mTORC1 substrates upon amino
      acid starvation. Cells expressing the hyperactive mTOR mutant displayed larger
      cell size in a normal growing condition and were resistant to cell size reduction
      and autophagy induction in an amino acid-starved condition. These results
      indicate that the activity of mTORC1 actually directs these cellular processes in
      response to nutrient status and confirm the biological functions of mTORC1, which
      had been proposed solely from loss-of-function analyses using rapamycin and
      (molecular)genetic techniques. Additionally, the hyperactive mTOR mutant did not
      induce cellular transformation of NIH/3T3 cells, suggesting that concomitant
      activation of additional pathways is required for tumorigenesis. This hyperactive
      mTOR mutant will be a valuable tool for establishing physiological consequences
      of mTOR activation in cells as well as in organisms.

PMID- 18812320
TI  - Phosphatidic acid phosphatase, a key enzyme in the regulation of lipid synthesis.

PMID- 18812321
TI  - Degradation of a cytosolic protein requires endoplasmic reticulum-associated
      degradation machinery.
AB  - Protein misfolding is monitored by a variety of cellular "quality control"
      systems. Endoplasmic reticulum (ER) quality control handles misfolded secretory
      and membrane proteins and is well characterized. However, less is known about the
      quality control of misfolded cytosolic proteins (CytoQC). To study CytoQC, we
      have employed a genetic system in Saccharomyces cerevisiae using a transplantable
      degron, CL1 (1). Attachment of CL1 to the cytosolic protein Ura3p destabilizes
      Ura3p, targeting it for rapid proteasomal degradation. We have performed a
      comprehensive analysis of Ura3p-CL1 degradation requirements. As shown
      previously, we observe that the ER-localized ubiquitin E2 (Ubc6p, Ubc7p, and
      Cue1p) and E3 (Doa10p) machinery involved in ER-associated degradation (ERAD) are
      also responsible for the degradation of the cytosolic substrate Ura3p-CL1.
      Importantly, we find that the cytosol/ER membrane-localized chaperones Ydj1p and
      Ssa1p, known to be necessary for the ERAD of membrane proteins with misfolded
      cytosolic domains, are also required for the ubiquitination and degradation of
      Ura3p-CL1. In addition, we show a role for the Cdc48p-Npl4p-Ufd1p complex in the
      degradation of Ura3p-CL1. When ubiquitination is blocked, a portion of Ura3p-CL1
      is ER membrane-localized. Furthermore, access to the cytosolic face of the ER is
      required for the degradation of CL1 degron-containing proteins. The ER is
      distributed throughout the cytosol, and our data, together with previous studies,
      suggest that the cytosolic face of the ER membrane serves as a "platform" for the
      degradation of Ura3p-CL1, which may also be the case for other CytoQC substrates.

PMID- 18812322
TI  - The proteomic constraint and its role in molecular evolution.
AB  - Recently, the concept of a "Proteomic Constraint" was introduced to explain the
      frequency of genetic code deviations in mitochondrial genomes. The Proteomic
      Constraint was proposed to be proportional to the size of the mitochondrially
      encoded proteome, hence small proteomes are expected to experience smaller total
      numbers of errors resulting from genetic code deviations, leading to less
      likelihood of causing lethality. The concept is now extended to encompass several
      other aspects of the genetic information system. When the Proteomic Constraint is
      small, it is proposed that there is little selective pressure to evolve or
      maintain error correction mechanisms, as a result of the smaller total number of
      errors that accumulate. Conversely, a large Proteomic Constraint is proposed to
      result in a correspondingly large selective pressure to evolve or maintain error
      correction mechanisms. Differences in the size of the Proteomic Constraint can
      help to explain differences in replicational, transcriptional, and translational
      fidelities between genomes. A key piece of evidence is the existence of negative
      power law relationships between proteome size and error rates; these are
      demonstrated to be diagnostic of the action of the Proteomic Constraint. The
      Proteomic Constraint is argued to be a major factor determining mutation rates in
      a diverse range of DNA genomes, implying that mutation rates are clock like. A
      small Proteomic Constraint partly explains why RNA viruses possess high mutation
      rates. A reduced Proteomic Constraint in intracellular pathogenic bacteria
      predicts a drift upwards in mutation rates. Differences in the Proteomic
      Constraint also appear to be linked to differences in recombination rates between
      eukaryotes. In addition, a reduced Proteomic Constraint may explain features of
      resident genomes, such as loss of DNA repair pathways, increased substitution
      rates, and AT biases, in addition to the occurrence of genetic code deviations.
      Thus, it is argued that the Proteomic Constraint is a universal factor that
      influences a wide range of properties of the genetic information system.

PMID- 18812323
TI  - Role of adjunctive thrombectomy and embolic protection devices in acute
      myocardial infarction: a comprehensive meta-analysis of randomized trials.
AB  - AIMS: Adjunctive thrombectomy and embolic protection devices in acute myocardial
      infarction have been extensively studied, although outcomes have mainly focused
      on surrogate markers of reperfusion. Therefore, the effect of adjunctive devices
      on clinical outcomes is unknown. This study sought to determine whether the use
      of a thrombectomy or embolic protection device during revascularization for acute
      myocardial infarction reduces mortality compared with percutaneous coronary
      intervention (PCI) alone. METHODS AND RESULTS: The Cochrane and Medline databases
      were searched for clinical trials that randomized patients with ST-elevation
      acute myocardial infarction to an adjuvant device prior to PCI compared with PCI
      alone. Devices were grouped into catheter thrombus aspiration, mechanical
      thrombectomy, and embolic protection. There were a total of 30 studies with 6415
      patients who met our selection criteria. Over a weighted mean follow-up of 5.0
      months, the incidence of mortality among all studies was 3.2% for the adjunctive
      device group vs. 3.7% for PCI alone (relative risk, 0.87; 95% confidence
      interval, 0.67-1.13). Among thrombus aspiration studies, mortality was 2.7% for
      the adjunctive device group vs. 4.4% for PCI alone (P = 0.018), for mechanical
      thrombectomy, mortality was 5.3% for the adjunctive device group vs. 2.8% for PCI
      alone (P = 0.050), and for embolic protection, mortality was 3.1% for the
      adjunctive device group vs. 3.4% for PCI alone (P = 0.69). CONCLUSION: Catheter
      thrombus aspiration during acute myocardial infarction is beneficial in reducing
      mortality compared with PCI alone. Mechanical thrombectomy appears to increase
      mortality, whereas embolic protection appears to have a neutral effect.

PMID- 18812324
TI  - On the use of Mendelian randomization to infer causality in observational
      epidemiology.

PMID- 18812325
TI  - Reduction of C-reactive protein with isoflavone supplement reverses endothelial
      dysfunction in patients with ischaemic stroke.
AB  - AIMS: To investigate the effect of oral isoflavone supplement on vascular
      endothelial function in patients with established cardiovascular disease. METHODS
      AND RESULTS: A randomized, double-blinded, placebo-controlled trial was performed
      to determine the effects of isoflavone supplement (80 mg/day, n = 50) vs. placebo
      (n = 52) for 12 weeks on brachial flow-mediated dilatation (FMD) in patients with
      prior ischaemic stroke. Compared with controls, FMD at 12 weeks was significantly
      greater in isoflavone-treated patients [treatment effect 1.0%, 95% confidence
      interval (95% CI) 0.1-2.0, P = 0.035]. Adjusted for baseline differences in FMD,
      isoflavone treatment was independently associated with significantly less
      impairment of FMD at 12 weeks (odds ratio 0.32, 95% CI 0.13-0.80, P = 0.014). The
      absolute treatment effect of isoflavone on brachial FMD was inversely related to
      baseline FMD (r = -0.51, P < 0.001), suggesting that vasoprotective effect of
      isoflavone was more pronounced in patients with more severe endothelial
      dysfunction. Moreover, isoflavone treatment for 12 weeks resulted in a
      significant decrease in serum high-sensitivity (hs)-C-reactive protein level
      (treatment effect -1.7 mg/L, 95% CI -3.3 to -0.1, P = 0.033). Nevertheless,
      isoflavone did not have any significant treatment effects on nitroglycerin
      mediated dilatation, blood pressure, heart rate, serum levels of fasting glucose
      and insulin, haemoglobin A1c, and oxidative stress as determined by serum
      superoxide dismutase, 8-isoprostane, and malondialdehyde (all P > 0.05).
      CONCLUSION: This study demonstrated that 12 week isoflavone treatment reduced
      serum hs-C-reactive protein and improved brachial FMD in patients with clinically
      manifest atherosclerosis, thus reversing their endothelial dysfunction status.
      These findings may have important implication for the use of isoflavone for
      secondary prevention in patients with cardiovascular disease, on top of
      conventional interventions.

PMID- 18812326
TI  - Transferring disease management and health promotion programs to other countries:
      critical success factors.
AB  - Governments and health service providers around the world are under pressure to
      improve health outcomes while containing rising healthcare costs. In response to
      such challenges, many regions have implemented services that have been successful
      in other countries-but 'importing' initiatives has many challenges. This article
      summarizes factors found to be critical to the success of adapting a US disease
      management and health promotion programme for use in Italy and the UK. Using
      three illustrative case studies, it describes how in each region the programme
      needed to adapt (i) the form and content of the disease management service, (ii)
      the involvement and integration with local clinicians and services and (iii) the
      evaluation of programme outcomes. We argue that it is important to implement
      evidence-based practice by learning lessons from other countries and service
      initiatives, but that it is equally important to take into consideration the
      '3Ps' that are critical for successful service implementation: payers,
      practitioners and patients.

PMID- 18812327
TI  - Rescue-stenting of an occluded lateral coronary sinus branch for recanalization
      after dissection during cardiac resynchronization device implantation.
AB  - Cardiac resynchronization therapy (CRT) using left- (LV) or biventricular pacing
      is widely applied in selected heart failure patients. However, transvenous LV
      lead placement into coronary sinus (CS) branches can be challenging. A 77-year
      old female patient with New York Heart Association class III symptoms due to
      dilated cardiomyopathy [LV ejection fraction (LVEF): 10%, QRS-duration: 150 ms],
      despite optimal medical treatment presented for CRT. Coronary sinus angiograms
      were performed after transvenous CS cannulation. Within a large posterolateral
      vein, low phrenic nerve stimulation thresholds were found. The only alternative
      smaller tortuous lateral branch showed a significant narrowing, making LV-lead
      advancement impossible. Angioplasty was performed, using a venoplasty balloon.
      This caused complete branch occlusion. After recanalization of the vessel by
      implantation of a bare metal stent, the lead could be advanced through the stent.
      Optimal pacing parameters without phrenic nerve stimulation were established.
      Angioplasty of CS branches during CRT implantation procedures bears the risk of
      complete branch occlusion, but recanalization can acutely be achieved by stent
      implantation. This is the first report on rescue-stenting of a CS branch after
      angioplasty-related occlusion. Transthoracic lead implantation, accompanied
      risks, and slower recovery could thus be avoided.

PMID- 18812328
TI  - Novel technique for imaging the pulmonary veins, left atrium, and oesophagus.

PMID- 18812329
TI  - Extrathoracic herniation of a lung bulla through a tube thoracostomy site.
AB  - We report a case of lung bulla herniation occurring two years after a tube
      thoracostomy application due to pneumothorax. A new bulla can develop or a pre
      existing bulla can herniate through a weak part of thoracic wall, a tube
      thoracostomy site as in our case. Diagnostic and radiological features of this
      uncommon case are described.

PMID- 18812330
TI  - Infarction-exclusion technique with the on-pump beating heart approach for
      ventricular septal perforation.
AB  - We report a successful surgical management of postinfarction ventricular septal
      perforation by infarction-exclusion technique with the on-pump beating heart
      approach and concomitant coronary artery bypass grafting. The identification of
      the suture line by direct inspection and finger palpation could be more accurate
      in determining contractile, thus viable myocardium supporting the patch, and
      concomitant coronary artery bypass grafting with on-pump beating heart could
      minimize the cardioplegia-induced myocardial damage.

PMID- 18812331
TI  - Establishing a role for intra-pleural fibrinolysis in managing traumatic
      haemothoraces.
AB  - A best evidence topic in thoracic surgery was written according to a structured
      protocol. The question addressed was whether there is a role in using intra
      pleural fibrinolysis or thrombolysis with an agent such as streptokinase aids in
      resolving haemothoraces following trauma. Twenty-four papers were identified
      using the search below. Eight papers presented the best evidence to answer the
      clinical question. The author, journal, date and country of publication, patient
      group studied, study type, relevant outcomes, results, and study weaknesses of
      the papers are tabulated. We conclude that intra-pleural fibrinolytic does have a
      role in managing patients with unresolved haemathoraces with complete resolution
      clinically and radiologically in most patients in half of the studies reviewed.
      It may be used as an alternative to surgical intervention in certain patients,
      but little work has been done on comparing intra-pleural fibrinolysis directly to
      surgical evacuation. The choice of agent and number of administrations are
      variable but with a similar outcome. Few studies have compared agents. The timing
      of when to use these agents following the traumatic haemothorax was variable but
      its use was commonly reserved following 'failure' of chest drainage clinically or
      radiologically (so usually over a week following the original injury). The
      overall morbidity including bleeding complications from their use was reported as
      low.

PMID- 18812332
TI  - Isolated papillary endothelial hyperplasia in the left atrial appendage.
AB  - Papillary endothelial hyperplasia (PEH) of the heart is extremely rare. This
      report describes a case of left atrial appendage PEH discovered by intraoperative
      palpation during mitral valve repair in a 69-year-old woman. The lesion was
      treated successfully by surgical excision of the left atrial appendage.
      Immunohistochemistry analysis confirmed the diagnosis and the patient was
      discharged without any complications.

PMID- 18812333
TI  - Aortic valve papillary fibroelastoma that developed rapidly after open-heart
      surgery.
AB  - The patient was a 76-year-old woman who underwent left atrial thrombectomy in
      November 2003 at our hospital. A mass adhered to the non-coronary aortic cusp was
      found during annual echocardiography, and the patient was admitted to our
      hospital. Transthoracic echocardiography detected two masses with pendulum-like
      movement: a 7-mm mass adhered to the non-coronary cusp and a 5-mm mass on the
      right coronary cusp. Papillary fibroelastoma was diagnosed based on the absence
      of inflammatory reactions or valvular destruction. Anticoagulant therapy was
      continued to prevent left atrial thrombus formation. At surgery, a 7-mm mass was
      adhered to the belly of the non-coronary cusp and a 5-mm pediculate mass was
      attached to a site near the nodule of Arantius of the right coronary cusp.
      Movable fibrous connective tissue 4 mm in length was present at two sites near
      the nodule of Arantius of the left coronary cusp, and these were also excised.
      All excised specimens, including those considered to be connective tissue, were
      found to be papillary fibroelastoma on pathological examination. Four papillary
      fibroelastomas that developed in all the cusps, including two small connective
      tissue-like morphologies and two sea anemone-like morphologies, indicated the
      process of papillary fibroelastoma growth and looked like 'a family'.

PMID- 18812334
TI  - Experience with pulmonary resection for extensively drug-resistant tuberculosis.
AB  - Extensively drug-resistant tuberculosis is becoming a global threat. It is a
      relatively new phenomenon, and its optimal management remains undetermined. We
      report our experience in using pulmonary resection for treating patients with
      this disease. Records were reviewed of 54 consecutive patients undergoing a
      pulmonary resection for multidrug-resistant tuberculosis at Fukujuji Hospital
      between 2000 and 2006. These patients were identified using the definition
      approved by the World Health Organization Global Task Force on extensively drug
      resistant tuberculosis in October 2006. Five (9%) patients (3 men and 2 women)
      aged 31-60 years met the definition. None of the patients was HIV-positive.
      Although the best available multidrug regimens were initiated, no patient could
      achieve sputum conversion. Adjuvant resectional surgery was considered because
      the patients had localized disease. Procedures performed included pneumonectomy
      (2) and upper lobectomy (3). There was no operative mortality or morbidity. All
      patients attained sputum-negative status after the operation, and they were
      maintained on multidrug regimens for 12-25 months postoperatively. All patients
      remained free from disease at the time of follow-up. Pulmonary resection under
      cover of state-of-the-art chemotherapy is safe and effective for patients with
      localized extensively drug-resistant tuberculosis.

PMID- 18812335
TI  - Congenital quadricuspid aortic valve associated with severe regurgitation.
AB  - A 56-year-old man was referred because of severe aortic regurgitation. He had a
      quadricuspid aortic valve with a small accessory cusp between the right coronary
      and noncoronary cusps. The ostium of the right coronary artery was deviated
      toward the accessory cusp commissure. Aortic valve replacement was performed with
      a bioprosthesis. The resected cusps showed fibrotic thickening with calcification
      and fenestration.

PMID- 18812336
TI  - A rare cause of dyspnea in adult: a right Bochdalek's hernia-containing colon.
AB  - Symptomatic cases of Bochdalek's hernia (BH) are uncommon in adults; symptoms
      arise only due to complications. Most of symptomatic cases are related to a left
      sided hernia. Right colon herniation in adults has never been reported. We
      present a case of a 70-year-old woman with right BH-containing colon. The patient
      was successfully treated by combined laparoscopic and thoracoscopic approach.

PMID- 18812337
TI  - Vacuum-assisted closure for mediastinitis after pediatric cardiac surgery.
AB  - Two children, aged 1 and 14 years with methicillin-resistant Staphylococcus
      aureus mediastinitis after pediatric open-heart surgery, were fitted with a
      vacuum-assisted closure system. Complete healing was achieved in both cases, and
      primary wound closure could be carried out without an omental flap after 6 and 16
      days.

PMID- 18812338
TI  - Mature cardiac myocyte hamartoma in the right atrium.
AB  - During coronary artery bypass grafting in a 58-year-old man, a mass was
      discovered incidentally in the right atrium, measuring 1.5 x 1 x 0.5 cm. It was
      composed of disorganized hypertrophic mature cardiac myocytes, and associated
      with focal fibrosis, mature adipocytes, and mild lymphocytic infiltration in
      peripheral areas, indicative of cardiac hamartoma. This type of hamartoma has
      been rarely reported as an isolated mass in the right atrium.

PMID- 18812339
TI  - STER science and cardiothoracic surgery: an Asian perspective.

PMID- 18812340
TI  - The use of PET and PET/CT scanning in lung cancer.

PMID- 18812341
TI  - Subcoronary implantation of a stentless valve in patients with aortic aneurysms.
AB  - Experience with a new operation for patients with aortic valve disease and
      aneurysm or dissection of the ascending aorta is described. Twenty-four patients
      aged 66-87 years were operated on using a subcoronary implantation technique with
      a stentless aortic valve bioprosthesis and an extension using a vascular tube
      prosthesis. No major adverse cardiac events were observed in the postoperative
      period. This operation offers a safe alternative to the technically more
      demanding procedures of composite bioprosthetic ascending aortic replacement or
      full root replacement.

PMID- 18812342
TI  - Surgery for sinus of valsalva aneurysm: 27-year experience with 100 patients.
AB  - Sinus of Valsalva aneurysm is a rare anomaly. This study was designed to assess
      the long-term outcome of surgical repair of sinus of Valsalva aneurysm and
      factors influencing the prognosis. From August 1980 to August sinus of Valsalva
      aneurysm repair. Ventricular septal defect (42) and aortic regurgitation (34)
      were the most frequent coexisting anomalies. An approach via the involved chamber
      was used in 60 patients, aortotomy in 5, and a combined approach in 35. Either
      direct (43) or patch (57) closure was used to repair the defect. Aortic valve
      replacement was required in 14 patients, and 8 needed valvuloplasty. Eighty
      patients were followed up for 15.6 +/- 3.9 years. There were 3 hospital deaths
      and 2 late deaths. New York Heart Association functional class improved
      significantly after surgery. Actuarial survival was 94% at 10 years, and 90% at
      15 years. Surgical treatment of sinus of Valsalva aneurysm is safe and effective,
      but late progressive aortic regurgitation is still a risk during long-term follow
      up, and early aggressive measures are recommended.

PMID- 18812343
TI  - Harmonic scalpel in video-assisted thoracoscopic thymic resections.
AB  - Video-assisted thoracoscopic thymectomy is safe, but the efficacy of this
      technique in thymomectomy is unproved. Data of 103 consecutive patients who had
      thoracoscopic thymectomy and thymomectomy between 1998 and 2006 were
      retrospectively reviewed. Conventional monopolar diathermy and endoscopic Liga
      clips were used in the first 50 patients, and the Harmonic Scalpel was employed
      in the next 53. Only mean tumor size differed between groups (56.6 +/- 18.2 vs
      40.0 +/- 20.8 mm in Harmonic Scalpel group). A similar number of patients had
      myasthenia gravis in the first group (72%) and Harmonic Scalpel group (83%).
      There were 49 thymomas (22 in first group, 27 in Harmonic Scalpel group). Of the
      earlier patients, 2 were re-explored for excessive chest tube drainage, 1 had
      ipsilateral phrenic nerve injury, and 2 had left phrenic nerves sacrificed
      intraoperatively due to thymoma invasion, but there was no significant difference
      in complications between groups. At a mean follow-up of 3.40 +/- 2.38 years
      (range, 0.04-8.52 years), there was 1 thymoma recurrence in the first group. Use
      of the Harmonic Scalpel in video-assisted thoracoscopic thymic resection is safe
      and confers some advantages over conventional methods of dissection.

PMID- 18812344
TI  - Interpleural morphine vs bupivacaine for postthoracotomy pain relief.
AB  - This prospective randomized double-blind trial was designed to compare the
      analgesic effects of interpleural bupivacaine and interpleural morphine for
      postthoracotomy pain management. Thirty-six American Society of Anesthesiologists
      class I and II patients undergoing an elective posterolateral thoracotomy were
      randomly divided into 2 groups of 18 each. Before chest closure, an interpleural
      catheter was inserted under direct vision. At the end of the operation and every
      4 hours thereafter, they received either 0.25% bupivacaine with epinephrine or
      0.2 mg x kg(-1) morphine sulfate interpleurally for 24 hours. The chest tubes
      were clamped during injection and for 15 min afterwards. Supplementary doses of
      intravenous morphine were given on request. The pain severity was evaluated at
      rest and on coughing before and 30 min after each interpleural injection, using
      an 11-point visual analog scale. Supplemental analgesic consumption and side
      effects were recorded. Both interpleural morphine and bupivacaine significantly
      reduced pain scores 30 min after each injection. However, pain scores and
      supplementary analgesic requirements were significantly lower in the interpleural
      morphine group. No serious side effects were detected in either group.
      Interpleural morphine provides better pain control than interpleural bupivacaine
      after a posterolateral thoracotomy.

PMID- 18812345
TI  - Prognostic variability in completely resected pN1 non-small-cell lung cancer.
AB  - We used the Tuscan Cancer Registry archives to retrieve records of 2,896 patients
      with a histological diagnosis of lung tumor from January 1996 to December 2000.
      Of 2,410 patients with non-small-cell lung cancer, 767 (31.8%) underwent complete
      resection. The following variables were analyzed for their influence on survival
      in the 157 patients with pathologic N1 status: sex, age, cell type, pathologic
      tumor status, number and level of involved lymph nodes, tumor grade, and type of
      surgery. Overall 5-year survival rates were 43.9% for 417 patients with pN0
      disease, 10.8% for 176 with pN2 disease, and 31.6% for those with pN1 disease. In
      pN1 disease, the overall 5-year survival rates for patients with hilar and non
      hilar lymph node involvement were 27.4% and 39.6%, respectively. Univariate
      analysis demonstrated that pathological T status and level of N1 involvement were
      significant prognostic factors. Cox proportional hazards analysis indicated that
      hilar lymph node involvement was an independent prognostic factor. N1 lymph node
      status was identified as an independent prognostic factor in a combination of
      subgroups with different prognoses.

PMID- 18812346
TI  - Factors influencing survival in patients after bidirectional Glenn shunt.
AB  - Clinical characteristics, echocardiographic values, and catheterization data of
      45 patients with a functional univentricular heart who had a bidirectional Glenn
      shunt instituted between November 1994 and October 2006 were retrospectively
      reviewed. Median age at operation was 20 months (range, 9 months to 19 years).
      Median follow-up time after the bidirectional Glenn operation was 4 years (range,
      1 day to 11 years). The early mortality rate was 4/45 (8.9%); overall mortality
      was 24.4%. Actuarial survival after a bidirectional Glenn shunt was 73% +/- 8% at
      5 years and 55% +/- 17% at 10 years. In multivariate Cox proportional hazards
      analysis, heterotaxy syndrome and systemic right ventricle were independent
      predictors of mortality after the bidirectional Glenn shunt. Age at operation,
      oxygen saturation, previous surgery, a pulsatile Glenn shunt, cardiopulmonary
      bypass, postoperative pulmonary artery pressure, bilateral superior venae cavae,
      and Nakata index were not predictive of mortality. The presence of heterotaxy
      syndrome and systemic right ventricle in patients with a functional
      univentricular heart should lead to aggressive investigation and management
      strategies.

PMID- 18812347
TI  - Clinical characteristics and surgery of primary lung cancer in younger patients.
AB  - Controversy exists regarding the clinical characteristics, pathological findings,
      and prognosis of patients < 50 years of age with primary lung cancer. The medical
      records of 4,556 patients diagnosed with primary lung cancer between 1980 and
      2004 were reviewed; of these, 305 were < 50 years old. Of 1,335 patients who were
      surgically treated, 122 were < 50 years old. Females were over-represented in the
      younger group. Younger patients had a significantly higher incidence of
      adenocarcinoma and large cell carcinoma, and a lower incidence of squamous cell
      carcinoma. The resectable rate in younger patients was significantly higher.
      Overall and among surgically treated patients, the survival rates of younger
      patients with stage 0-I disease were significantly better than those of older
      patients. Younger patients with early-stage primary lung cancer had a
      significantly better prognosis than older patients, although survival in the
      advanced stages was not significantly different.

PMID- 18812348
TI  - One-stage procedure for lung and liver hydatid cysts.
AB  - Concomitant pulmonary and liver hydatid cysts occur in 4% 25% of patients with
      echinococcosis. To evaluate the safety of a single-stage operation, experience
      with this procedure between 1992 and 2005 was reviewed. Of 152 patients who
      underwent surgery for pulmonary hydatid cyst, 30 had an additional hepatic cyst
      that was located on the upper dome of the liver in all cases. Pulmonary cysts
      were excised first via a posterolateral thoracotomy. After phrenotomy, the
      hepatic hydatid cyst was evacuated without capitonnage, and a Folly catheter was
      left in the cavity. Postoperative complications in the 30 patients with cysts in
      both locations included empyema in 2, bronchopleural fistula in 1, excessive
      biliary discharge in 3 and hemorrhage in 1. Hepatic hydatid cysts recurred in 2
      patients. There was no hospital death. A single-stage posterolateral thoracotomy
      for extraction of pulmonary and liver hydatid cyst is an effective and safe
      surgical technique with few complications.

PMID- 18812349
TI  - Verapamil and nitroglycerin improves the patency rate of radial artery grafts.
AB  - The best way to prevent spasm of the radial artery is still under investigation.
      We retrospectively compared the effectiveness of topical verapamil-nitroglycerin
      with papaverine in preventing graft spasm in 215 patients who underwent isolated
      conventional coronary artery bypass using a radial artery. Postoperative
      angiographic data were successfully collected in 116 patients. Perioperative
      radial artery graft spasm was observed in 2 patients in the papaverine group and
      1 in the verapamil-nitroglycerin group; this difference was not considered
      significant. Complete or functional occlusion was detected by postoperative
      angiography in 13 grafts (10 in the papaverine group and 3 in the verapamil
      nitroglycerin group). Multivariate regression analysis revealed that topical
      papaverine and grafting to the right coronary artery significantly increased the
      rate of occlusion of radial artery grafts. Although further studies are needed,
      our data support the view that topical verapamil-nitroglycerin reduces the
      incidence of radial artery graft occlusion.

PMID- 18812350
TI  - Ventricular restoration by linear endoventricular patchplasty and linear repair.
AB  - Surgical ventricular restoration improves cardiac function in patients with large
      left ventricular aneurysms. Aneurysm repair techniques have evolved to geometric
      repair by exclusion of the aneurysmal area with a circular patch. But even
      circular endoventricular patchplasty may result in a less elliptical ventricle.
      We modified the techniques of both linear and geometric repair. The early and
      intermediate outcomes in 102 patients with post-infarction left ventricular
      aneurysm, treated between 2001 and 2004, were analyzed. Concomitant procedures
      included coronary artery bypass grafting in 73 patients, mitral valve repair in
      29, cryoablation in 3, and post-infarction ventricular septal rupture repair in
      3. Overall mortality was 12.7%. Left ventricular ejection fraction increased
      significantly postoperatively, from 31.5% +/- 6.5% to 34.2% +/- 5.9%. There were
      significant decreases in end-diastolic volumes from 140.3 +/- 38.3 to 100.8 +/-
      33.5 mL, and end-systolic volumes from 95.1 +/- 26.1 to 66.0 +/- 21.7 mL. These
      benefits continued at the 12- to 52-month follow-up. Our modified technique
      restores a near physiological left ventricular geometry and has a favorable
      clinical outcome.

PMID- 18812351
TI  - Postinfarction heart rupture of posterior wall repaired by covering patch.
AB  - A 46-year-old man underwent emergency surgery for heart rupture after acute
      infarction of the posterior wall. Echocardiography revealed limited myocardial
      thinning, so rather than sutureless repair, a covering patch was used in view of
      the risk of recurrent rupture. Postoperative echocardiography showed the
      myocardial thinning had progressed to a wide defect, and computed tomography
      demonstrated that the covering patch had prevented a repeat rupture.

PMID- 18812352
TI  - Pure yolk-sac tumor of the lung.
AB  - Primary germ cell tumors of the chest often localize in the anterior mediastinal
      compartment. Such tumors originating from lungs and pleura are rare. Chest
      tomography revealed a mass in the middle lobe of the right lung in a 25-year-old
      man. A middle lobe medial segmentectomy was performed, and chemotherapy was
      applied postoperatively.

PMID- 18812353
TI  - Surgical palliation for Taussig-Bing anomaly with multiple lesions.
AB  - A successful surgical palliative procedure, consisting of an arterial switch
      operation, pulmonary artery banding, and arch repair, was performed in a neonate
      with Taussig-Bing anomaly and aortic arch interruption, subaortic stenosis, and
      multiple muscular ventricular septal defects. Such anatomical complexity made
      treatment difficult. This palliative procedure allows future biventricular
      repair.

PMID- 18812354
TI  - Two easy ways to ensure safe sternotomy and sternal closure.
AB  - Appropriate sternotomy and sternal closure are the most important factors in
      mechanical stability of the sternum and prevention of several postoperative
      complications. Easy techniques for identifying the sternal midline to facilitate
      opening and for obtaining reinforced closure are described. These techniques
      require minimal additional time. They are particularly indicated in patients at
      risk of sternotomy-related complications, and helpful to young surgeons in
      training.

PMID- 18812355
TI  - Simple and reliable distal anastomosis for total aortic arch replacement.
AB  - In total aortic arch replacement, distal aortic anastomosis is often remarkably
      difficult because of the deep operative field. Once bleeding from the anastomotic
      area occurs, it is intractable not only because of technical problems but also
      decreased coagulability due to deep hypothermia and the fragility of the aortic
      wall. We describe a simple but reliable strategy for distal anastomosis, which is
      unique with regard to the approach to the anastomotic area and the anastomotic
      method.

PMID- 18812356
TI  - Mechanical circulatory support: a clinical reality.
AB  - Mechanical circulatory support is becoming an alternative therapeutic option for
      patients in cardiogenic shock or advanced cardiac failure who cannot be improved
      by maximal medical therapy. More than 30 years of engineering development and
      clinical research have led to a level of efficacy and reliability of ventricular
      assist devices, which allows promotion of this approach for the most difficult
      patients. Uses include a gaining-time strategy as a bridge to cardiac
      transplantation or recovery of native cardiac function, as well as permanent
      support with the device. The large variety of devices permits every cardiac
      surgical unit, even those not used to cardiac transplantation, to propose this
      option to the patient. Recent experience with small silent implantable pumps
      suggests that the pioneering period of mechanical circulatory support is probably
      over, and the time has come for precise prospective trials to optimize both
      patient selection and the timing for utilization. In countries where cardiac
      transplantation has not developed, there is now an easily accessible technique
      for management of patients with cardiac failure.

PMID- 18812357
TI  - Chronic constrictive calcific pericarditis.

PMID- 18812358
TI  - Spontaneous pneumomediastinum involving carotid artery neurovascular pedicle.

PMID- 18812359
TI  - Traumatic ventricular septal defect.

PMID- 18812360
TI  - Is the use of self-rated health measures to assess health inequalities
      misleading?

PMID- 18812361
TI  - Commentary: Comments on the diversity in associations between community social
      capital and health.

PMID- 18812362
TI  - Commentary: Russia's mortality crisis, alcohol and social transformation.

PMID- 18812363
TI  - Intelligence in girls and their subsequent smoking behaviour as mothers: the 1958
      National Child Development Study and the 1970 British Cohort Study.
AB  - BACKGROUND: Exposure to tobacco smoke either in utero or postnatally can have
      substantial adverse effects on child health, yet many women continue to smoke
      during pregnancy and after the birth. How women's intelligence in childhood
      affects their smoking behaviour as mothers is unclear. METHODS: The participants
      were from two British national birth cohorts: 3325 women aged 33 years from the
      1958 National Child Development Study and 1971 women aged 34 years from the 1970
      British Cohort Study. We used structural equation modelling to examine the direct
      and indirect effects of intelligence measured at age 10-11 years, parental and
      current social class, educational attainment and age at first birth on smoking
      during pregnancy and current smoking status. RESULTS: Forty per cent of women in
      the 1958 cohort smoked during pregnancy, compared with 28% of those from the 1970
      cohort. In both cohorts, women with lower IQ in childhood were more likely as
      adults to smoke during pregnancy and to be a smoker currently. Structural
      equation modelling showed that the effects of childhood IQ on smoking behaviour
      were indirect, as they were statistically mediated by educational attainment and
      age at first birth. There was some effect of educational attainment and age at
      first birth on smoking behaviour over and above the effect of intelligence.
      CONCLUSION: Childhood intelligence influenced women's smoking behaviour as
      mothers primarily through its contributions to educational attainment and age at
      first birth.

PMID- 18812364
TI  - Integrating and annotating the interactome using the MiMI plugin for cytoscape.
AB  - The MiMI molecular interaction repository integrates data from multiple sources,
      resolves interactions to standard gene names and symbols, links to annotation
      data from GO, MeSH and PubMed and normalizes the descriptions of interaction
      type. Here, we describe a Cytoscape plugin that retrieves interaction and
      annotation data from MiMI and links out to multiple data sources and tools.
      Community annotation of the interactome is supported. AVAILABILITY: MiMI plugin
      v3.0.1 can be installed from within Cytoscape 2.6 using the Cytoscape plugin
      manager in 'Network and Attribute I/0' category. The plugin is also preloaded
      when Cytoscape is launched using Java WebStart at http://mimi.ncibi.org by
      querying a gene and clicking 'View in MiMI Plugin for Cytoscape' link.

PMID- 18812365
TI  - DOCKGROUND protein-protein docking decoy set.
AB  - A protein-protein docking decoy set is built for the Dockground unbound benchmark
      set. The GRAMM-X docking scan was used to generate 100 non-native and at least
      one near-native match per complex for 61 complexes. The set is a publicly
      available resource for the development of scoring functions and knowledge-based
      potentials for protein docking methodologies. AVAILABILITY: The decoys are freely
      available for download at
      http://dockground.bioinformatics.ku.edu/UNBOUND/decoy/decoy.php

PMID- 18812367
TI  - Valuing the well connected.

PMID- 18812366
TI  - Effects of improved home heating on asthma in community dwelling children:
      randomised controlled trial.
AB  - OBJECTIVE: To assess whether non-polluting, more effective home heating (heat
      pump, wood pellet burner, flued gas) has a positive effect on the health of
      children with asthma. DESIGN: Randomised controlled trial. SETTING: Households in
      five communities in New Zealand. PARTICIPANTS: 409 children aged 6-12 years with
      doctor diagnosed asthma. INTERVENTIONS: Installation of a non-polluting, more
      effective home heater before winter. The control group received a replacement
      heater at the end of the trial. MAIN OUTCOME MEASURES: The primary outcome was
      change in lung function (peak expiratory flow rate and forced expiratory volume
      in one second, FEV(1)). Secondary outcomes were child reported respiratory tract
      symptoms and daily use of preventer and reliever drugs. At the end of winter 2005
      (baseline) and winter 2006 (follow-up) parents reported their child's general
      health, use of health services, overall respiratory health, and housing
      conditions. Nitrogen dioxide levels were measured monthly for four months and
      temperatures in the living room and child's bedroom were recorded hourly.
      RESULTS: Improvements in lung function were not significant (difference in mean
      FEV(1) 130.7 ml, 95% confidence interval -20.3 to 281.7). Compared with children
      in the control group, however, children in the intervention group had 1.80 fewer
      days off school (95% confidence interval 0.11 to 3.13), 0.40 fewer visits to a
      doctor for asthma (0.11 to 0.62), and 0.25 fewer visits to a pharmacist for
      asthma (0.09 to 0.32). Children in the intervention group also had fewer reports
      of poor health (adjusted odds ratio 0.48, 95% confidence interval 0.31 to 0.74),
      less sleep disturbed by wheezing (0.55, 0.35 to 0.85), less dry cough at night
      (0.52, 0.32 to 0.83), and reduced scores for lower respiratory tract symptoms
      (0.77, 0.73 to 0.81) than children in the control group. The intervention was
      associated with a mean temperature rise in the living room of 1.10 degrees C (95%
      confidence interval 0.54 degrees C to 1.64 degrees C) and in the child's bedroom
      of 0.57 degrees C (0.05 degrees C to 1.08 degrees C). Lower levels of nitrogen
      dioxide were measured in the living rooms of the intervention households than in
      those of the control households (geometric mean 8.5 microg/m(3) v 15.7
      microg/m(3), P<0.001). A similar effect was found in the children's bedrooms (7.3
      microg/m(3) v 10.9 microg/m(3), P<0.001). CONCLUSION: Installing non-polluting,
      more effective heating in the homes of children with asthma did not significantly
      improve lung function but did significantly reduce symptoms of asthma, days off
      school, healthcare utilisation, and visits to a pharmacist. TRIAL REGISTRATION:
      Clinical Trials NCT00489762.

PMID- 18812368
TI  - Judge allows disclosure of workers' medical records after death.

PMID- 18812369
TI  - America's health choices.

PMID- 18812370
TI  - Improving palliative care in Africa.

PMID- 18812371
TI  - Health and the US presidential campaigns.

PMID- 18812372
TI  - Ibuprofen increases soft tissue infections in children.

PMID- 18812373
TI  - Closing the gap between generations.

PMID- 18812374
TI  - Inequity in the market place.

PMID- 18812375
TI  - Outcome in infants exposed to methadone in utero.

PMID- 18812376
TI  - Experience of directive in the Netherlands.

PMID- 18812377
TI  - Policy to reduce the risk costs the environment dear.

PMID- 18812378
TI  - Lessons health care can learn from aviation.

PMID- 18812379
TI  - Who else but pharma will fund medical education?

PMID- 18812380
TI  - Some progress in UK psychiatry.

PMID- 18812381
TI  - Matters arising from industry link to education.

PMID- 18812382
TI  - More reasons for caution with statins and other such.

PMID- 18812383
TI  - Authors have missed gap between theory and reality.

PMID- 18812384
TI  - The joy of diversity.

PMID- 18812385
TI  - Effect of short-term macrophage depletion in the development of posterior capsule
      opacification in rodents.
AB  - AIM: To evaluate the role of macrophages in the development of posterior capsule
      opacification (PCO). METHODS: For this purpose, an extracapsular lens extraction
      was performed in 18 consecutive Sprague-Dawley rats. Animals were treated with
      liposomal clodronate (Cl(2)MDP-lip-treated group, n = 10) or phosphate-buffered
      saline (PBS) (control group, n = 8) 1 day preoperatively and on the first day
      postoperatively, and sacrificed 3 days postoperatively. Masked clinical, light
      microscopy and immunohistochemistry studies were conducted. The Fisher exact test
      and randomisation test were used to assess statistically differences between
      groups. RESULTS: A statistically significant reduction in the number of
      macrophages (ED1+, ED7+, ED8+) was found in the Cl(2)MDP-lip-treated group
      compared with the PBS-lip-treated group (p = 0.048, p = 0.004, p = 0.027,
      respectively). There were no statistically significant differences with regards
      to the presence/absence of central opacification (p = 0.29) and capsular
      wrinkling (p = 0.21) as detected clinically between groups. Similarly, a
      qualitative evaluation of the degree of PCO with regards to lens epithelial cell
      (LEC) proliferation, capsular wrinkling and Soemmerring ring formation showed no
      statistically significance between groups (p = 0.27, p = 0.061, p = 1.0,
      respectively). However, a statistically significant reduction in the number of
      lens epithelial cells (LEC) counted in the centre of the posterior capsule was
      found in the Cl(2)MDP-lip-treated group (p = 0.009). CONCLUSION: Depletion of
      macrophages was accompanied by a reduction in LEC in the centre of the posterior
      capsule in rodents.

PMID- 18812386
TI  - Retraction. Blepharo-conjunctivitis due to Leishmania (Viannia) Braziliensis
      cutaneous infection: report of two cases in Rio de Janeiro, Brazil.

PMID- 18812388
TI  - Conjunctival fixation sutures for refractory superior limbic
      keratoconjunctivitis.

PMID- 18812387
TI  - Expression of heat shock protein 27 and alpha-crystallins in human retinoblastoma
      after chemoreduction.
AB  - AIM: Small heat shock proteins (sHSP) play an important role in the resistance to
      anticancer drugs. We examined the expression of the sHSP family, HSP27 and alpha
      crystallins, in human retinoblastoma with and without preoperative chemotherapy.
      METHODS: Eighteen enucleated eyes from patients with retinoblastoma were used.
      Six patients had undergone chemotherapy before enucleation. Formalin-fixed,
      paraffin-embedded tissue sections were processed for H&E staining and examined by
      immunohistochemistry using anti-HSP27 and alpha-crystallins antibodies. RESULTS:
      Eleven of 12 cases with no history of preoperative chemotherapy showed weakly
      positive or negative staining for HSP27, whereas six and five cases were strongly
      positive for alphaA and alphaB-crystallin, respectively. In the six cases with a
      history of chemotherapy, several viable retinoblastoma cells remained.
      Immunoreactivity for HSP27 and alphaB-crystallin was strongly detected in the
      cytoplasm of viable retinoblastoma cells, while alphaA-crystallin
      immunoreactivity was less marked. Immunoreactivity for HSP27 was significantly
      higher in retinoblastoma cases with preoperative chemotherapy than in those
      without chemotherapy (p<0.0001). In contrast, immunoreactivity for alphaA
      crystallin was significantly lower in cases with chemotherapy than in cases
      without chemotherapy (p<0.01). CONCLUSIONS: HSP27 and alphaB-crystallin, but not
      alphaA-crystallin, were highly expressed in viable tumour cells after
      chemotherapy, suggesting that HSP27 and alphaB-crystallin may protect tumour
      cells from apoptotic signals produced by anticancer drugs in retinoblastoma.

PMID- 18812389
TI  - Canada, chrysotile, and the search for truth.

PMID- 18812390
TI  - Validation of transferability of DBA derivatization and LC-MS/MS determination
      method for isocyanates via an interlaboratory comparison.
AB  - An adapted method for the quantitative determination of isocyanates in air was
      implemented and validated in-house. The method was based on air sampling using an
      impinger flask containing di-n-butylamine (DBA) in toluene and a glass fibre
      filter in series. The DBA derivatives were determined using liquid chromatography
      and tandem mass spectrometry. Studied isocyanates were isophorone diisocyanate,
      isocyanic acid (ICA), methyl isocyanate, ethyl isocyanate, propyl isocyanate,
      hexamethylene diisocyanate (HDI), 2,6- and 2,4-toluene diisocyanate, 4,4'
      methylene diphenyl diisocyanate (MDI), phenyl isocyanate (PhI), MDI oligomers and
      different HDI adducts. Monitoring of selected reactions resulted in
      quantifications with correlation coefficients >0.995, within-batch relative
      standard deviation (RSD) of repeatability was <13% for all analytes. Between
      batch RSD (reproducibility) was determined for all the compounds with the
      exception of the adducts and oligomers and was also <13%. As an additional
      validation procedure, the method was evaluated by exchanging field (air) and
      standard samples between two laboratories. The RSDs observed by the two
      laboratories were comparable. The concentrations determined were between 80 and
      120% of each other, depending on the analyte and the individual concentrations.
      The method was applied in a large field study on exposure of workers in car
      repair shops and industrial painters with >500 samples.

PMID- 18812391
TI  - Condom use among injection drug users accessing a supervised injecting facility.
AB  - OBJECTIVES: Although supervised injecting facility (SIF) use has been associated
      with reductions in injection-related risk behaviours, the impact of SIFs on the
      sexual behaviour of injection drug users (IDUs) has not been thoroughly
      investigated. Therefore, we examined the patterns and predictors of condom use
      among SIF users in Vancouver, Canada. METHODS: We performed a longitudinal
      analysis of the factors associated with consistent condom use among IDUs
      recruited from within a SIF. RESULTS: Among 1090 individuals, 650 (59.6%)
      reported a sexual partner in the past 6 months at baseline. Consistent condom use
      was reported by 108 (25.3%) and 205 (61.6%) individuals reporting regular or
      casual partners, respectively. After 2 years of observation, these proportions
      increased to 32.9% and 69.8%, respectively. In multivariate analysis, predictors
      of consistent condom use with regular partners included HIV positivity (adjusted
      odds ratio (AOR) 2.23; 95% CI 1.51 to 3.31), injecting with a sex partner (AOR
      0.50; 95% CI 0.37 to 0.68), enrollment in addiction treatment (AOR 0.68, 95% CI
      0.52 to 0.89) and time since recruitment (AOR 1.29; 95% CI 1.06 to 1.55 per
      year). Predictors of consistent condom use with casual partners included HIV
      positivity (AOR 1.70; 95% CI 1.03 to 2.81), syringe borrowing (AOR 0.54; 95% CI
      0.32 to 0.91) and syringe lending (AOR 0.52; 95% CI 0.32 to 0.84). CONCLUSIONS:
      Our results demonstrate that among SIF users, consistent condom use was more
      frequent among casual sex partners and among HIV positive individuals.
      Importantly, while the prevalence of consistent condom use was low at baseline,
      it increased over time. Our findings suggest a possible beneficial effect of the
      SIF on safer sexual practices.

PMID- 18812392
TI  - Patient-initiated delay at a genitourinary medicine clinic: are there public
      health consequences?
AB  - OBJECTIVES: To assess the public health consequence of patients electing not to
      be seen within 48 hours in a genitourinary medicine (GUM) clinic. METHODS: A 3
      month retrospective case notes review was carried out for 310 new and re-book
      patients who chose to wait for more than 48 hours to be seen. RESULTS:
      Altogether, 10% (310/3110) of patients opted to be seen beyond 48 h. Their median
      wait was 6 days including weekends and 4 days excluding weekends. Demographic
      details did not vary except for the male to female ratio of 1:1.7 (1:1 in
      patients seen within 48 h). We found that no symptomatic patients or asymptomatic
      contacts of those with known sexually transmitted infections (STIs) reported sex
      with a new partner after booking their appointment. No patient reported sex with
      a recently treated partner who consequently required re-treatment and none
      suffered a complication of a STI. In addition, there were no cases of new HIV
      infection in this group and the rates of STIs were similar compared with patients
      seen within 48 hours of contacting the unit. CONCLUSIONS: Despite 10% of patients
      choosing to delay attendance beyond 48 h, no adverse public health outcomes were
      demonstrated.

PMID- 18812393
TI  - Risk factors for a first thrombotic event in antiphospholipid antibody carriers.
      A multicentre, retrospective follow-up study.
AB  - OBJECTIVES: To asses risk factors for a first thrombotic event in
      antiphospholipid antibody (aPL) positive carriers and evaluate the efficacy of
      prophylactic treatments. METHODS: Recruitment criteria were age 18-65 years, no
      history of thrombosis, positivity for lupus anticoagulant and/or IgG/IgM
      anticardiolipin antibody (aCL) on > or =2 occasions at least 6 weeks apart.
      Demographic, laboratory and clinical parameters were collected at enrolment and
      at the time of the thrombotic event. RESULTS: 370 patients/subjects (mean (SD)
      age 34 (9.9) years) were analysed retrospectively for a mean (SD) follow-up of
      59.3 (45.5) months. Thirty patients (8.1%) developed a first thrombotic event
      during follow-up. Hypertension and medium/high levels of IgG aCL were identified
      by multivariate logistic regression analysis as independent risk factors for
      thrombosis. Thromboprophylaxis during high-risk and long-term periods was
      significantly protective. CONCLUSIONS: Hypertension or medium/high titres of IgG
      aCL are risk factors for a first thrombotic event in asymptomatic aPL carriers
      and primary prophylaxis is protective.

PMID- 18812394
TI  - Homozygosity for DNASE2 single nucleotide polymorphisms in the 5'-regulatory
      region is associated with rheumatoid arthritis.
AB  - OBJECTIVES: To analyse the distribution of single nucleotide polymorphisms (SNPs)
      in the 5'-regulatory region of the DNASE2 gene, in patients with rheumatoid
      arthritis (RA) and healthy controls. METHODS: A total of 906 patients with RA and
      878 healthy controls were genotyped. All subjects were of German Caucasian
      origin. Genotyping was performed by real-time polymerase chain reaction
      technology, using a TaqMan 5'-allele discrimination assay. RESULTS: In the
      initial analysis of unrelated case-control samples, three DNASE2 SNP alleles in
      the 5'-regulatory region were significantly more frequent in patients with RA
      than in healthy controls. The strongest association was found for the -1066G
      allele (33.5% vs 27.2%, p = 0.007, odds ratio (OR) = 1.34). Homozygosity for this
      allele (genotype GG) resulted in an additional increase in disease susceptibility
      (12.5% vs 6.2%, OR = 2.17). The association was replicated in a second case
      control series of 483 patients with RA from two German multicentre studies and
      474 controls. The association of DNASE2 -1066 GG homozygosity with RA was limited
      to rheumatoid factor-positive disease, but was not influenced by the presence of
      anti-cyclic citrullinated peptide or antinuclear antibodies. Similarly, the
      presence or absence of the HLA-DRB1 shared epitope or the RA-associated PTPN22
      allele had no influence on this association. CONCLUSIONS: The association of SNPs
      in the 5'-regulatory region of the DNA degrading enzyme DNASE2 with RA implies a
      role for this enzyme in the pathogenesis of this autoimmune disease.

PMID- 18812395
TI  - GabiPD: the GABI primary database--a plant integrative 'omics' database.
AB  - The GABI Primary Database, GabiPD (http://www.gabipd.org/), was established in
      the frame of the German initiative for Genome Analysis of the Plant Biological
      System (GABI). The goal of GabiPD is to collect, integrate, analyze and visualize
      primary information from GABI projects. GabiPD constitutes a repository and
      analysis platform for a wide array of heterogeneous data from high-throughput
      experiments in several plant species. Data from different 'omics' fronts are
      incorporated (i.e. genomics, transcriptomics, proteomics and metabolomics),
      originating from 14 different model or crop species. We have developed the
      concept of GreenCards for text-based retrieval of all data types in GabiPD (e.g.
      clones, genes, mutant lines). All data types point to a central Gene GreenCard,
      where gene information is integrated from genome projects or NCBI UniGene sets.
      The centralized Gene GreenCard allows visualizing ESTs aligned to annotated
      transcripts as well as displaying identified protein domains and gene structure.
      Moreover, GabiPD makes available interactive genetic maps from potato and barley,
      and protein 2DE gels from Arabidopsis thaliana and Brassica napus. Gene
      expression and metabolic-profiling data can be visualized through MapManWeb. By
      the integration of complex data in a framework of existing knowledge, GabiPD
      provides new insights and allows for new interpretations of the data.

PMID- 18812396
TI  - Zinc Finger Database (ZiFDB): a repository for information on C2H2 zinc fingers
      and engineered zinc-finger arrays.
AB  - Zinc fingers are the most abundant DNA-binding motifs encoded by eukaryotic
      genomes and one of the best understood DNA-recognition domains. Each zinc finger
      typically binds a 3-nt target sequence, and it is possible to engineer zinc
      finger arrays (ZFAs) that recognize extended DNA sequences by linking together
      individual zinc fingers. Engineered zinc-finger proteins have proven to be
      valuable tools for gene regulation and genome modification because they target
      specific sites in a genome. Here we describe ZiFDB (Zinc Finger Database;
      http://bindr.gdcb.iastate.edu/ZiFDB), a web-accessible resource that compiles
      information on individual zinc fingers and engineered ZFAs. To enhance its
      utility, ZiFDB is linked to the output from ZiFiT--a software package that
      assists biologists in finding sites within target genes for engineering zinc
      finger proteins. For many molecular biologists, ZiFDB will be particularly
      valuable for determining if a given ZFA (or portion thereof) has previously been
      constructed and whether or not it has the requisite DNA-binding activity for
      their experiments. ZiFDB will also be a valuable resource for those scientists
      interested in better understanding how zinc-finger proteins recognize target DNA.

PMID- 18812397
TI  - Enhanced gene trapping in mouse embryonic stem cells.
AB  - Gene trapping is used to introduce insertional mutations into genes of mouse
      embryonic stem cells (ESCs). It is performed with gene trap vectors that
      simultaneously mutate and report the expression of the endogenous gene at the
      site of insertion and provide a DNA tag for rapid identification of the disrupted
      gene. Gene traps have been employed worldwide to assemble libraries of mouse ESC
      lines harboring mutations in single genes, which can be used to make mutant mice.
      However, most of the employed gene trap vectors require gene expression for
      reporting a gene trap event and therefore genes that are poorly expressed may be
      under-represented in the existing libraries. To address this problem, we have
      developed a novel class of gene trap vectors that can induce gene expression at
      insertion sites, thereby bypassing the problem of intrinsic poor expression. We
      show here that the insertion of the osteopontin enhancer into several
      conventional gene trap vectors significantly increases the gene trapping
      efficiency in high-throughput screens and facilitates the recovery of poorly
      expressed genes.

PMID- 18812398
TI  - S-box and T-box riboswitches and antisense RNA control a sulfur metabolic operon
      of Clostridium acetobutylicum.
AB  - The ubiGmccBA operon of Clostridium acetobutylicum is involved in methionine to
      cysteine conversion. We showed that its expression is controlled by a complex
      regulatory system combining several RNA-based mechanisms. Two functional
      convergent promoters associated with transcriptional antitermination systems, a
      cysteine-specific T-box and an S-box riboswitch, are located upstream of and
      downstream from the ubiG operon, respectively. Several antisense RNAs were
      synthesized from the downstream S-box-dependent promoter, resulting in modulation
      of the level of ubiG transcript and of MccB activity. In contrast, the upstream T
      box system did not appear to play a major role in regulation, leaving antisense
      transcription as the major regulatory mechanism for the ubiG operon. The
      abundance of sense and antisense transcripts was inversely correlated with the
      sulfur source availability. Deletion of the downstream promoter region completely
      abolished the sulfur-dependent control of the ubiG operon, and the expression of
      antisense transcripts in trans did not restore the regulation of the operon. Our
      data revealed important insights into the molecular mechanism of cis-antisense
      mediated regulation, a control system only rarely observed in prokaryotes. We
      proposed a regulatory model in which the antisense RNA controlled the expression
      of the ubiG operon in cis via transcriptional interference at the ubiG locus.

PMID- 18812399
TI  - 14-3-3 activation of DNA binding of p53 by enhancing its association into
      tetramers.
AB  - Activation of the tumour suppressor p53 on DNA damage involves post-translational
      modification by phosphorylation and acetylation. Phosphorylation of certain
      residues is critical for p53 stabilization and plays an important role in DNA
      binding activity. The 14-3-3 family of proteins activates the DNA-binding
      affinity of p53 upon stress by binding to a site in its intrinsically disordered
      C-terminal domain containing a phosphorylated serine at 378. We have screened
      various p53 C-terminal phosphorylated peptides for binding to two different
      isoforms of 14-3-3, epsilon and gamma. We found that phosphorylation at either
      S366 or T387 caused even tighter binding to 14-3-3. We made by semi-synthesis a
      tetrameric construct comprised of the tetramerization plus C-terminal domains of
      p53 that was phosphorylated on S366, S378 and T387. It bound 10 times tighter
      than did the monomeric counterpart to dimeric 14-3-3. We showed indirectly from
      binding curves and directly from fluorescence-detection analytical
      ultracentrifugation that 14-3-3 enhanced the binding of sequence-specific DNA to
      p53 by causing p53 dimers to form tetramers at lower concentrations. If the in
      vitro data extrapolate to in vivo, then it is an attractive hypothesis that p53
      activity may be subject to control by accessory proteins lowering its tetramer
      dimer dissociation constant from its normal value of 120-150 nM.

PMID- 18812400
TI  - Serial analysis of mutation spectra (SAMS): a new approach for the determination
      of mutation spectra of site-specific DNA damage and their sequence dependence.
AB  - Many mutations occur as a result of DNA synthesis past the site of DNA damage by
      DNA damage bypass polymerases. The frequency and types of mutations not only
      depend on the nature of the damage, but also on the sequence context, as revealed
      from analysis of mutation spectra of DNA exposed to mutagens. Herein we report a
      new method for the rapid determination of the effect of sequence context on
      mutagenesis called SAMS for serial analysis of mutation spectra. This technique
      makes use of the methodology that underlies serial analysis of gene expression
      (SAGE) to analyze mutations that result from DNA synthesis past a DNA lesion site
      specifically embedded in a library of DNA sequences. To illustrate our technique
      we determined the effect of sequence context on mutations generated by DNA
      synthesis past a tetrahydrofuran abasic site model by the DNA damage bypass
      polymerase yeast polymerase eta.

PMID- 18812401
TI  - Megasatellites: a peculiar class of giant minisatellites in genes involved in
      cell adhesion and pathogenicity in Candida glabrata.
AB  - Minisatellites are DNA tandem repeats that are found in all sequenced genomes. In
      the yeast Saccharomyces cerevisiae, they are frequently encountered in genes
      encoding cell wall proteins. Minisatellites present in the completely sequenced
      genome of the pathogenic yeast Candida glabrata were similarly analyzed, and two
      new types of minisatellites were discovered: minisatellites that are composed of
      two different intermingled repeats (called compound minisatellites), and
      minisatellites containing unusually long repeated motifs (126-429 bp). These long
      repeat minisatellites may reach unusual length for such elements (up to 10 kb).
      Due to these peculiar properties, they have been named 'megasatellites'. They are
      found essentially in genes involved in cell-cell adhesion, and could therefore be
      involved in the ability of this opportunistic pathogen to colonize the human
      host. In addition to megasatellites, found in large paralogous gene families,
      there are 93 minisatellites with simple shorter motifs, comparable to those found
      in S. cerevisiae. Most of the time, these minisatellites are not conserved
      between C. glabrata and S. cerevisiae, although their host genes are well
      conserved, raising the question of an active mechanism creating minisatellites de
      novo in hemiascomycetes.

PMID- 18812402
TI  - Identification of two conserved aspartic acid residues required for DNA digestion
      by a novel thermophilic Exonuclease VII in Thermotoga maritima.
AB  - Exonuclease VII was first identified in 1974 as a DNA exonuclease that did not
      require any divalent cations for activity. Indeed, Escherichia coli ExoVII was
      identified in partially purified extracts in the presence of EDTA. ExoVII is
      comprised of two subunits (XseA and XseB) that are highly conserved and present
      in most sequenced prokaryotic genomes, but are not seen in eukaryotes. To better
      understand this exonuclease family, we have characterized an ExoVII homolog from
      Thermotoga maritima. Thermotoga maritima XseA/B homologs TM1768 and TM1769 were
      co-expressed and purified, and show robust nuclease activity at 80 degrees C.
      This activity is magnesium dependent and is inhibited by phosphate ions, which
      distinguish it from E. coli ExoVII. Nevertheless, both E. coli and T. maritima
      ExoVII share a similar putative active site motif with two conserved aspartate
      residues in the large (XseA/TM1768) subunit. We show that these residues, Asp235
      and Asp240, are essential for the nuclease activity of T. maritima ExoVII. We
      hypothesize that the ExoVII family of nucleases can be sub-divided into two sub
      families based on EDTA resistance and that T. maritima ExoVII is the first member
      of the branch that is characterized by EDTA sensitivity and inhibition by
      phosphate.

PMID- 18812403
TI  - Prospective cohort study to test the predictability of the Cardiff and Vale
      paediatric early warning system.
AB  - OBJECTIVE: To develop and test the predictability of a paediatric early warning
      score to identify children at risk of developing critical illness. DESIGN:
      Prospective cohort study. SETTING: Admissions to all paediatric wards at the
      University Hospital of Wales. OUTCOME MEASURES: Respiratory arrest, cardiac
      arrest, paediatric high-dependency unit admission, paediatric intensive care unit
      admission and death. RESULTS: Data were collected on 1000 patients. A single
      abnormal observation determined by the Cardiff and Vale paediatric early warning
      system (C&VPEWS) had a 89.0% sensitivity (95% CI 80.5 to 94.1), 63.9% specificity
      (95% CI 63.8 to 63.9), 2.2% positive predictive value (95% CI 2.0 to 2.3) and a
      99.8% negative predictive value (95% CI 99.7 to 99.9) for identifying children
      who subsequently had an adverse outcome. The area under the receiver operating
      characteristic curve for the C&VPEWS score was 0.86 (95% CI 0.82 to 0.91).
      CONCLUSION: Identifying children likely to develop critical illness can be
      difficult. The assessment tool developed from the advanced paediatric life
      support guidelines on identifying sick children appears to be sensitive but not
      specific. If the C&VPEWS was used as a trigger to activate a rapid response team
      to assess the child, the majority of calls would be unnecessary.

PMID- 18812404
TI  - 20p12.3 microdeletion predisposes to Wolff-Parkinson-White syndrome with variable
      neurocognitive deficits.
AB  - BACKGROUND: Wolff-Parkinson-White syndrome (WPW) is a bypass re-entrant
      tachycardia that results from an abnormal connection between the atria and
      ventricles. Mutations in PRKAG2 have been described in patients with familial WPW
      syndrome and hypertrophic cardiomyopathy. Based on the role of bone morphogenetic
      protein (BMP) signalling in the development of annulus fibrosus in mice, it has
      been proposed that BMP signalling through the type 1a receptor and other
      downstream components may play a role in pre-excitation. METHODS AND RESULTS:
      Using the array comparative genomic hybridisation (CGH), we identified five
      individuals with non-recurrent deletions of 20p12.3. Four of these individuals
      had WPW syndrome with variable dysmorphisms and neurocognitive delay. With the
      exception of one maternally inherited deletion, all occurred de novo, and the
      smallest of these harboured a single gene, BMP2. In two individuals with
      additional features of Alagille syndrome, deletion of both JAG1 and BMP2 were
      identified. Deletion of this region has not been described as a copy number
      variant in the Database of Genomic Variants and has not been identified in 13 321
      individuals from other cohort examined by array CGH in our laboratory.
      CONCLUSIONS: Our findings demonstrate a novel genomic disorder characterised by
      deletion of BMP2 with variable cognitive deficits and dysmorphic features and
      show that individuals bearing microdeletions in 20p12.3 often present with WPW
      syndrome.

PMID- 18812405
TI  - 2q23.1 microdeletion identified by array comparative genomic hybridisation: an
      emerging phenotype with Angelman-like features?
AB  - BACKGROUND: Genome-wide screening of patients with mental retardation using array
      comparative genomic hybridisation (CGH) has identified several novel imbalances.
      With this genotype-first approach, the 2q22.3q23.3 deletion was recently
      described as a novel microdeletion syndrome. The authors report two unrelated
      patients with a de novo interstitial deletion mapping in this genomic region and
      presenting similar "pseudo-Angelman" phenotypes, including severe psychomotor
      retardation, speech impairment, epilepsy, microcephaly, ataxia, and behavioural
      disabilities. METHODS: The microdeletions were identified by array CGH using
      oligonucleotide and bacterial artificial chromosome (BAC) arrays, and further
      confirmed by fluorescence in situ hybridisation (FISH) and semi-quantitative
      polymerase chain reaction (PCR). RESULTS: The boundaries and sizes of the
      deletions in the two patients were different but an overlapping region of about
      250 kb was defined, which mapped to 2q23.1 and included two genes: MBD5 and EPC2.
      The SIP1 gene associated with the Mowat-Wilson syndrome was not included in the
      deleted genomic region. DISCUSSION: Haploinsufficiency of one of the deleted
      genes (MBD5 or EPC2) could be responsible for the common clinical features
      observed in the 2q23.1 microdeletion syndrome, and this hypothesis needs further
      investigation.

PMID- 18812406
TI  - Haematological malignancies presenting with acute liver injury: a single-centre
      experience.
AB  - INTRODUCTION: Early recognition and identification of the underlying cause of
      acute liver injury (ALI) is crucial in instituting medical treatment and
      assessing the need for liver transplantation. Haematological malignancies have
      been reported to present as ALI with progression to acute liver failure but
      experience is limited. AIM: Review our experience of ALI secondary to
      haematological malignancies. PATIENTS AND METHODS: Patients admitted to the liver
      unit with ALI secondary to a haematological malignancy between 1996 and 2006 were
      identified. A retrospective review was made of their case notes and our database.
      RESULTS: Of the 752 cases of ALI, six cases of ALI secondary to haematological
      malignancy were identified. Common features were a prodromal illness (median
      duration of 5 weeks; range 2-6 weeks) and jaundice (median bilirubin 208
      micromol/l; range 112-238 micromol/l). The majority of patients (5/6) had
      hepatomegaly. Liver biopsy was performed in two patients and confirmed the
      diagnosis in both cases. In other cases, the diagnosis was made following lymph
      node biopsy (1), bone marrow examination (2) or from post-mortem examination (1).
      Median time from jaundice to encephalopathy was 12 days; range 1-22 days. A
      single patient underwent liver transplantation but died in the immediate post
      operative period. All patients died soon after admission with a median survival
      of 8 days (range 3-26 days). CONCLUSION: Haematological malignancy should be
      considered in ALI patients presenting with a prodromal illness, jaundice and
      hepatomegaly. Biopsy is essential to confirm the diagnosis but the benefit of
      definitive therapy such as chemotherapy and/or transplantation in this setting is
      unclear and survival is poor.

PMID- 18812407
TI  - How dangerous is echocardiographic contrast?

PMID- 18812408
TI  - Bifurcation stenting: current strategies and new devices.
AB  - Based on the results of numerous randomised trials, the provisional approach of
      implanting one stent on the main branch has become the default approach to most
      bifurcation lesions. However, bifurcation intervention still remains technically
      challenging. Dedicated bifurcation stents have been designed to specifically
      treat coronary bifurcations with the aim of dealing with some of the shortcomings
      of the conventional percutaneous approach to bifurcation intervention. Most of
      the devices are aimed at facilitating the provisional approach. They are an
      exciting and innovative technology that may further simplify the management and
      current approach to bifurcation treatment. Currently, 11 devices are available
      that have either completed or are currently undergoing First-In-Man trials. The
      development of more drug-eluting platforms and larger studies with control groups
      demonstrating their clinical applicability, efficacy and safety are required
      before they are widely incorporated into daily practice.

PMID- 18812409
TI  - Exercise testing and exercise stress echocardiography in asymptomatic aortic
      valve stenosis.
AB  - Management of asymptomatic patients with severe aortic valve stenosis (AVS)
      remains a source of debate. Exercise testing is no longer contraindicated and
      needs now to be considered when evaluating asymptomatic patients with AVS.
      Several studies have clearly demonstrated that exercise-elicited symptoms during
      conventional upright exercise portends clinical events. Semi-supine exercise with
      continuous Doppler echocardiography monitoring elicits cardiovascular
      abnormalities that are not detected at rest. Abnormal left ventricular response
      to exercise and/or major increase in mean transvalvular gradient add to the
      prognostic value of elicited symptoms in asymptomatic patients with severe AVS.
      However, preliminary experience needs to be confirmed to warrant routine use of
      exercise Doppler echocardiography in the evaluation of patients with asymptomatic
      AVS.

PMID- 18812410
TI  - Self-efficacy moderates the relation between declines in physical activity and
      perceived social support in high school girls.
AB  - OBJECTIVE: To test whether self-efficacy for overcoming barriers to physical
      activity has direct, indirect (i.e., mediated), or moderating relations with
      naturally occurring change in perceived social support and declines in physical
      activity during high school. METHODS: Latent growth modeling was used with
      measures completed in the 8th, 9th, and 12th grades by a cohort of 195 Black and
      White girls. RESULTS: Self-efficacy was stable and moderated the relation between
      changes in physical activity and perceived social support. Girls who maintained a
      perception of strong social support had less of a decline in physical activity if
      they also had high self-efficacy. However, girls having high self-efficacy had a
      greater decline in physical activity if they perceived declines in social
      support. CONCLUSIONS: Randomized controlled trials of physical activity
      interventions based on social cognitive theory should consider that the influence
      of girls' perceptions of social support on their physical activity may differ
      according to their efficacy beliefs about barriers to physical activity.

PMID- 18812411
TI  - The impact of a newly designed resilience-enhancing programme on parent- and
      teacher-perceived resilience environment among Health Promoting Schools in Hong
      Kong.
AB  - BACKGROUND: The Health Promoting School (HPS) approach provides a strong
      foundation to improve students' overall health, including psychological well
      being, which has its roots in resilience. The present study evaluates the
      effectiveness of a resilience-enhancing programme, building on the concept of HPS
      among a Chinese population. METHODOLOGY: All mainstream schools in a socially
      disadvantaged region of Hong Kong were eligible, and stratified random sampling
      was used to recruit both HPS as intervention schools and non-HPS as control
      schools. The participants included teachers and parents of grade 3 and 5 primary
      and grade 1 secondary school students (aged 8, 10 and 12 respectively). Validated
      surveys were used to assess resilience scores in both groups of schools before
      and after a series of resilience-enhancing activities in HPS, and ANOVA was used
      to compare the score changes between the two groups. RESULTS: Five primary and
      four secondary HPS and four primary and four secondary non-HPS were recruited,
      involving 4918 parents and 602 teachers. Among primary and secondary parents, the
      HPS group did not report a higher score than the non-HPS group. Among secondary
      teachers, the HPS group showed significantly higher scores than the non-HPS group
      (p = 0.023 to < 0.001) CONCLUSION: The present study is the first to demonstrate
      the positive synergistic effect of a newly designed resilience-enhancing
      intervention programme, building on the concept of HPS in schools among secondary
      teachers in Hong Kong. It was suggested that future initiatives may involve
      parent networking and school-family collaboration in fostering an even more
      resilient school environment.

PMID- 18812412
TI  - "God bless General Peron": DDT and the endgame of malaria eradication in
      Argentina in the 1940s.
AB  - This article explores the politics of malaria eradication in Argentina during the
      first government of Juan D. Peron. The article develops the theme of historical
      convergence to understand the rapid mobilization and success of the climactic
      battle against malaria in Northwest Argentina. The nearly complete eradication of
      malaria in Argentina resulted from a combination of three factors. First, Carlos
      Alvarado, the director of Argentina's Malaria Service, had already developed a
      solid but flexible organizational base that allowed a dramatic change in control
      strategy. Second, an infusion of new technologies, especially DDT but also motor
      vehicles, was instrumental. Lastly, a radical reorientation of national public
      health policy in the 1940s, under the direction of Peron and his health minister,
      Ramon Carrillo, encouraged eradication. These figures embraced and refashioned
      long-standing organicist ideologies that hitched the strength of the nation-state
      to the health and vigor of its ordinary citizens. This ideological orientation
      was reflected in bold, populist political strategies that showcased swift,
      massive, and expensive public health campaigns, including malaria eradication. In
      the conclusion, the article explores the ambiguous connections between malaria
      eradication and an ecological perspective on the disease.

PMID- 18812413
TI  - Social cognition in schizophrenia: a review of face processing.
AB  - BACKGROUND: People with schizophrenia have difficulties in interpreting social
      information. Much social information is gathered from faces, and face processing
      represents a well-characterized model to study the basis of social deficits in
      schizophrenia. SOURCES OF DATA: A narrative review of selected literature. AREAS
      OF AGREEMENT: Individuals with schizophrenia have impairments in recognizing
      basic emotions and making social judgements from facial stimuli. Areas of
      controversy The neural basis of these abnormalities is still being determined.
      However, initial evidence implicates dysfunction of frontal and temporal lobe
      brain regions. Hyper-activation of the amygdala, a brain region involved in fear,
      to facial stimuli may be an important underlying neural abnormality. GROWING
      POINTS: The present article highlights the difficulties that people with
      schizophrenia have in interpreting social cues from faces. AREAS TIMELY FOR
      DEVELOPING RESEARCH: Research is required to understand more about both the basis
      of social deficits in schizophrenia and their potential remediation.

PMID- 18812414
TI  - Is tendon pathology a continuum? A pathology model to explain the clinical
      presentation of load-induced tendinopathy.
AB  - Overuse tendinopathy is problematic to manage clinically. People of different
      ages with tendons under diverse loads present with varying degrees of pain,
      irritability, and capacity to function. Recovery is similarly variable; some
      tendons recover with simple interventions, some remain resistant to all
      treatments. The pathology of tendinopathy has been described as degenerative or
      failed healing. Neither of these descriptions fully explains the heterogeneity of
      presentation. This review proposes, and provides evidence for, a continuum of
      pathology. This model of pathology allows rational placement of treatments along
      the continuum. A new model of tendinopathy and thoughtful treatment
      implementation may improve outcomes for those with tendinopathy. This model is
      presented for evaluation by clinicians and researchers.

PMID- 18812415
TI  - Are "exercise pills" the answer to the growing problem of physical inactivity?

PMID- 18812416
TI  - Vibration therapy reduces plasma IL6 and muscle soreness after downhill running.
AB  - OBJECTIVE: In this study, the effects of vibration therapy (VT) on delayed-onset
      muscle soreness (DOMS) and associated inflammatory markers after downhill running
      were determined. METHODS: 29 male recreational runners (33 (8) years; V(O2)peak
      57 (6) ml kg(-1) min(-1)) completed a 40-min downhill run and were randomly
      allocated to a VT group or Control group. For 5 days post-run, the VT group
      underwent once-daily sessions of VT on the upper and lower legs. DOMS was
      assessed pre-run and for 5 days post-run by visual analogue scale. Immune cell
      subsets and plasma inflammatory markers were assessed pre-run, post-run, 24 and
      120 h post-run by full differential cell count, and by ELISA and enzyme
      immunoassay, respectively. Data were analysed as per cent change from pre-run
      (ANOVA) and the magnitude of the treatment effect (Cohen's effect size
      statistics). RESULTS: VT significantly reduced calf pain 96 h post-run (-50%
      (40%), 90% confidence limits) and gluteal pain 96 h (-50% (40%)) and 120 h post
      run (-30% (30%)); decreased interleukin 6 (IL6) 24 h (-46% (31%)) and 120 h post
      run (-65% (30%)); substantially decreased histamine 24 h (-40% (50%)) and 120 h
      post-run (-37% (48%)); substantially increased neutrophils (8.6% (8.1%)) and
      significantly decreased lymphocytes (-17% (12%)) 24 h post-run. There were no
      clear substantial effects of VT on other leukocyte subsets and inflammatory
      markers. CONCLUSION: VT reduces muscle soreness and IL6. It may stimulate
      lymphocyte and neutrophil responses and may be a useful modality in treating
      muscle inflammation.

PMID- 18812417
TI  - The reliability measurements of lateral scapular slide test at three different
      degrees of shoulder joint abduction.
AB  - BACKGROUND: Lateral scapular slide test (LSST) quantitatively measures the
      distance between thoracic spine (T7) and inferior angle of scapula. OBJECTIVE: In
      this study, the intra-rater reliability, inter-rater reliability and diagnostic
      accuracy of LSST were measured using a caliper. METHODS: Three measurements of
      each test position were obtained bilaterally. Intraclass correlation coefficient
      (ICC) (2.1), 95% CI and 2 SEMs were calculated for intra-rater and inter-rater
      reliability of the absolute scapular distance. Sensitivity, specificity, positive
      and negative likelihood ratios were determined. RESULTS: 27 people with and 30
      people without shoulder pain participated. The mean age (SD) for the participant
      was 47.7 (11.6) years and 33.5 (11.7) years, respectively. The ICCs for intra
      rater reliability were high. A range of poor to good ICCs was found for inter
      rater reliability. The 2 SEMs ranged from 4.6 to 7.9 mm for intra-rater
      reliability and from 6.8 to 13.4 mm for inter-rater reliability for people with
      shoulder pain. Positive and negative likelihood ratios from 0.94 to 1.22 and from
      0.21 to 2.5, respectively, were demonstrated. CONCLUSION: SST did not show a
      consistent high reliability. The diagnostic accuracy of the LSST was low, which
      questions the clinical importance of the tests outcomes.

PMID- 18812418
TI  - Behavioural and social correlates of sedentary time in young people.
AB  - OBJECTIVE: In this study, behavioural and social correlates of objectively
      measured sedentary time in young people were identified. DESIGN: Cross-sectional
      analysis of data from the European Youth Heart Study (EYHS). SETTING: Schools in
      Denmark, Estonia, Portugal and Norway. PARTICIPANTS: Respondents were invited
      using a twostage cluster sampling procedure. Analyses include 2107 children (9-10
      years old) and adolescents (14-15 years old). ASSESSMENT OF INDEPENDENT
      VARIABLES: Seven behavioural and 15 social variables assessed by parental and
      computerised child questionnaires. MAIN OUTCOME MEASURE: Sedentary activity as
      assessed by accelerometry (10 min blocks at <200 counts/min). Analyses were
      stratified by country, and interactions with grade and sex were investigated.
      RESULTS: Adolescents were more sedentary than children (335.4 (90.4 min/day) vs
      217.2 (75.6 min/day), p<0.001). Patterns of associations differed across
      countries. High computer use and no television viewing before school in Norway,
      and being sedentary during school breaks in Estonia were positively associated
      with sedentary time. No behavioural variables were associated with sedentary time
      in the Danish and Portuguese models. Socioeconomic position was positively
      associated with sedentary time in Portugal and Estonia, father's body mass index
      negatively in the Estonian model. Norwegian participants with a game console at
      home and Portuguese participants with a television in their bedroom were more
      sedentary. CONCLUSIONS: A single strategy aimed at reducing sedentary behaviour
      is unlikely to be effective across Europe as the target populations and
      behaviours of focus differ between countries. Targeting high socioeconomic groups
      in Portugal and Estonia or focusing on reducing computer use in Norway might be
      effective intervention strategies to reduce overall sedentary time.

PMID- 18812419
TI  - Treatment of osteitis pubis and osteomyelitis of the pubic symphysis in athletes:
      a systematic review.
AB  - OBJECTIVES: The authors examined the most current evidence for treatment options
      in athletes with osteitis pubis and osteomyelitis pubis, attempting to determine
      which options provide optimal pain relief with rapid return to sport and
      prevention of symptom reoccurrence. METHODS: Three databases-MEDLINE, Cochrane
      Database of Systematic Reviews and CINAHL-were searched using the OVID interface
      for all years between 1985 and May 2008. References were analysed from included
      studies, and additional relevant articles were obtained for inclusion. Inclusion
      criteria included (1) humans only, (2) subjects had no apparent risk factors for
      development of osteitis pubis or osteomyelitis of the pubic symphysis other than
      athletic involvement, (3) both physical exam findings and diagnostic imaging were
      used to confirm either diagnosis, and (4) a definitive treatment strategy was
      identifiable for management of osteitis pubis or osteomyelitis of the pubic
      symphysis. In total, 25 articles were included in the review. RESULTS: There were
      no randomised controlled trials identified with this study's search strategy. A
      total of 195 athletes were diagnosed as having osteitis pubis (186 males, nine
      females) and treated with either conservative measures/physical therapy, local
      injection with corticosteroids and/or local anaesthetic, dextrose prolotherapy,
      surgery or antibiotic therapy. Six case reports/series described conservative
      treatment measures (physical therapy, rest, non-steroid anti-inflammatory drugs).
      Four case series explored the use of corticosteroid injections in treatment. One
      case series described the use of dextrose prolotherapy as a treatment modality.
      Six case series described various surgical techniques (pubic symphysis curettage,
      polypropylene mesh placement and pubic bone stabilisation) in treatment. Ten case
      reports/series (10 subjects) outlined antibiotic treatment of osteomyelitis of
      the pubic symphysis. CONCLUSIONS: The current medical literature shows only level
      4 evidence of the treatment for osteitis pubis in 24 case reports/series in
      athletes. Without any direct comparison of treatment modalities, it is difficult
      to determine which individual treatment option is the most efficacious. Further
      study comparing the different treatment options is necessary to determine which
      modality provides the fastest return to sport.

PMID- 18812420
TI  - Higher fasting plasma glucose levels within the normoglycaemic range and rotator
      cuff tears.
AB  - OBJECTIVE: To determine the plasma glucose levels in non-diabetic patients with
      rotator cuff tear. DESIGN: Frequency-matched case-control study. SETTING:
      University Teaching Hospital. PARTICIPANTS: The study included 194 subjects who
      were operated on at our institution. Group 1 included 97 consecutive patients (36
      men and 61 women; mean age: 62.9 years, range 37 to 82) who underwent
      arthroscopic repair of a rotator cuff tear in 2007 and 2008. Group 2 (control
      group) included 97 patients (36 men and 61 women; mean age: 61.6 years, range 36
      to 80) who underwent arthroscopic meniscectomy for a meniscal tear in the same
      period, and had no evidence of shoulder pathology. These patients were frequency
      matched by age (within 3 years) and gender with patients of Group 1. MAIN OUTCOME
      MEASURE: Measurement of fasting plasma glucose levels. RESULTS: Patients with
      rotator cuff tears (Group 1) showed statistically significantly higher fasting
      plasma glucose levels within the normoglycaemic range (p = 0.007) than patients
      with meniscal tear (Group 2). CONCLUSIONS: The present study suggests that
      normal, but in the high range of normal, increasing plasma glucose levels may be
      a risk factor for rotator cuff tear. An enhanced understanding of these factors
      holds the promise of new approaches to the prevention and management of rotator
      cuff tears.

PMID- 18812421
TI  - Differential elevation of matrix metalloproteinase expression in women exposed to
      levonorgestrel-releasing intrauterine system for a short or prolonged period of
      time.
AB  - BACKGROUND: The levonorgestrel-releasing intrauterine system (LNG-IUS) is an
      effective contraceptive and has many non-contraceptive health benefits. However,
      it is commonly associated with irregular endometrial bleeding. Metalloproteinases
      contribute to extracellular matrix (ECM) remodelling and regulate bleeding during
      the menstrual cycle. Enhanced metalloproteinase expression participates in the
      pathogenesis of breakthrough bleeding. Thus the objective of this study was to
      compare matrix metalloproteinase (MMP) expression in endometrium during luteal
      phase and in short-term (1 month) and long-term (> or =6 months) LNG-IUS users.
      METHODS: MMP expression was analysed by semi-quantitative RT-PCR and
      immunohistochemistry. Gelatinase activity was determined by gelatin zymography.
      RESULTS: MMP-1, -2, -3, -7, -9 and -12 mRNAs levels were increased, whereas that
      of MMP-26 was decreased in the endometrium of LNG-IUS users. MMP-1, -2, -3, -7
      and -9 were localized by immunohistochemistry in all biopsies in the short-term
      group but in only 0-27% in the control group. The incidence of positive
      immunostaining for MMP-2 and -3 decreased significantly in the long-term compared
      with short-term LNG-IUS users. MMP-26 was localized in all biopsies from the
      control group but in only 14 and 25% from the short- and long-term LNG-IUS
      groups, respectively. In both LNG groups, the numbers of macrophages (the major
      source of MMP-12) was increased. CONCLUSIONS: MMP-1, active MMP-2, MMP-3, MMP-7,
      MMP-9 and MMP-12 are more prevalent in the short-term LNG-IUS group, suggesting
      their important contribution to ECM breakdown and transient bleeding. The
      decrease in the percentage of women expressing MMP-2 and -3 might contribute to
      the decreased occurrence of unwanted spotting and bleeding in long-term LNG-IUS
      users.

PMID- 18812422
TI  - Use of letrozole in assisted reproduction: a systematic review and meta-analysis.
AB  - BACKGROUND: Letrozole is the third-generation aromatase inhibitor (AI) most
      widely used in assisted reproduction. AIs induce ovulation by inhibiting estrogen
      production; the consequent hypoestrogenic state increases GnRH release and
      pituitary follicle-stimulating hormone (FSH) synthesis. METHODS: A systematic
      search of the literature was performed for both prospective and retrospective
      studies. Meta-analyses of randomized clinical trials (RCTs) were performed for
      three comparisons: letrozole versus clomiphene citrate (CC), letrozole + FSH
      versus FSH in intrauterine insemination (IUI) and letrozole + FSH versus FSH in
      IVF. In the absence of RCTs, non-randomized studies were pooled. RESULTS: Nine
      studies were included in the meta-analysis. Four RCTs compared the overall effect
      of letrozole with CC in patients with polycystic ovary syndrome. The pooled
      result was not significant for ovulatory cycles (OR = 1.17; 95% CI 0.66-2.09), or
      for pregnancy rate per cycle (OR = 1.47; 95% CI 0.73-2.96) or for pregnancy rate
      per patient (OR = 1.37; 95% CI 0.70-2.71). In three retrospective studies which
      compared L + FSH with FSH in ovarian stimulation for IUI, the pooled OR was 1.15
      (95% CI 0.78-1.71). A final meta-analysis included one RCT and one cohort study
      that compared letrozole + gonadotrophin versus gonadotrophin alone: the pooled
      pregnancy rate per patient was not significantly different (OR = 1.40; 95% CI
      0.67-2.91). CONCLUSIONS: Letrozole is as effective as other methods of ovulation
      induction. Further randomized-controlled studies are warranted to define more
      clearly the efficacy and safety of letrozole in human reproduction.

PMID- 18812423
TI  - Pre-medication practices and incidence of infusion-related reactions in patients
      receiving AMPHOTEC: data from the Patient Registry of Amphotericin B Cholesteryl
      Sulfate Complex for Injection Clinical Tolerability (PRoACT) registry.
AB  - BACKGROUND: Clinical studies have suggested that rates of infusion-related
      reactions (IRRs) may be higher with amphotericin B colloidal dispersion (ABCD)
      versus other forms of amphotericin B. However, these studies did not permit the
      use of pre-medications upfront, which are now commonly used. Objectives To
      describe the use of pre-medications and determine the rate of IRRs in the real
      world setting. METHODS: PRoACT, a multicentre, worldwide observational registry,
      captured real-world data about pre-medication practices and IRRs in patients
      receiving ABCD. Eligible patients were those beginning treatment with ABCD;
      treatment was according to the site's standard treatment practice. Incidence of
      IRRs was collected during the first 10 days of ABCD therapy. Clinical response
      data were collected 12 weeks after treatment start. RESULTS: One hundred and
      seventy patients from 21 worldwide sites were included (median age 37 years; 52%
      male). There were a total of 1230 ABCD infusions (mean dose 2.8 mg/kg/day); 90%
      of the infusions (1105/1230) had pre-medication. Common pre-medications included
      corticosteroids, antihistamines, paracetamol (acetaminophen) and metamizole. The
      overall IRR rate was 12% (147/1230) and was lower in infusions with pre
      medication (11%) versus no pre-medication (22%), P < 0.001. Corticosteroids were
      associated with a decreased incidence of IRRs (P < 0.05), while paracetamol and
      antihistamines were not. The most common IRRs were chills (7%), fever (7%) and
      rigors (5%). Clearance of the fungal infection occurred in 52% of the
      participants. CONCLUSIONS: These data suggest a lower rate of IRRs with ABCD than
      previously reported. Pre-medication is associated with decreased IRR incidence.
      Corticosteroids in particular appear to decrease IRRs while paracetamol and
      antihistamines, though commonly used, do not.

PMID- 18812424
TI  - Complete nucleotide sequence of pKP96, a 67 850 bp multiresistance plasmid
      encoding qnrA1, aac(6')-Ib-cr and blaCTX-M-24 from Klebsiella pneumoniae.
AB  - OBJECTIVES: The multiresistance plasmid pKP96 from Klebsiella pneumoniae was
      sequenced completely and analysed concerning its genetic environment and
      distributing of antimicrobial resistance genes. METHODS: The complete sequence of
      the plasmid was determined using a whole-genome shotgun approach. MICs of 13
      antimicrobial agents were determined using Etests. A conjugation experiment was
      performed in liquid medium. RESULTS: pKP96 is a circularly closed 67 850 bp
      multiresistance plasmid with an IncN incompatibility group. Seventy putative
      genes were identified according to the annotation of the finished sequence. The
      backbone region of the plasmid, comprising the conjugal transfer and plasmid
      replication regions, showed 91% identity to the IncN plasmid R46. Several mobile
      elements were found to be inserted into pKP96 together with antimicrobial
      resistance genes, including qnrA1, aac(6')-Ib-cr and bla(CTX-M-24). CONCLUSIONS:
      Plasmid pKP96 is a chimera that has acquired its multiple antimicrobial
      resistance determinants horizontally from different sources. It may have evolved
      from an ancestor plasmid similar to R46 through the stepwise events of
      integration or recombination.

PMID- 18812425
TI  - Arrival of Klebsiella pneumoniae producing KPC carbapenemase in the United
      Kingdom.
AB  - BACKGROUND: KPC-type carbapenemases are increasingly prevalent in parts of the
      USA and Israel and are an emerging concern in South America, Europe and China. We
      investigated the UK's first two KPC-producing Klebsiella pneumoniae isolates.
      METHODS: The isolates were referred to the UK's national reference laboratory for
      confirmation of carbapenem resistance. Susceptibilities were determined by agar
      dilution, and bla(KPC) and Tn4401-like elements were sought by PCR and
      sequencing. Isolates were compared by PFGE of XbaI- and SpeI-digested genomic
      DNA. RESULTS: The isolates were from patients in different UK hospitals, with no
      epidemiological connection. Both were resistant to carbapenems (MICs > 16 mg/L),
      with imipenem MICs unchanged by EDTA, and also to all other beta-lactams
      (including inhibitor combinations), tobramycin, amikacin and ciprofloxacin. They
      were susceptible to gentamicin (MICs </= 1 mg/L) and colistin (MICs </= 0.5
      mg/L), with intermediate susceptibility to tigecycline (MICs 1-2 mg/L). The
      isolates belonged to the same PFGE-defined strain, highly related to a
      disseminated KPC-producing strain characterized previously in Tel Aviv, Israel.
      Like this Israeli strain, the UK isolates produced KPC-3 carbapenemase, with the
      bla(KPC-3) gene located within a Tn4401-like element. CONCLUSIONS: The first KPC
      3-producing K. pneumoniae isolates detected in the UK were highly genetically
      related to a KPC-3-producing Israeli K. pneumoniae strain. This relatedness was
      consistent with the history of one UK patient, who had been hospitalized
      previously in Israel. However, this strain may be circulating more widely since
      the second UK patient had no identifiable links with Israel or other overseas
      countries.

PMID- 18812426
TI  - Bacterial colonization of polymer brush-coated and pristine silicone rubber
      implanted in infected pockets in mice.
AB  - OBJECTIVES: Curing biomaterial-associated infection (BAI) frequently includes
      antibiotic treatment, implant removal and re-implantation. However, revision
      implants are at a greater risk of infection as they may attract bacteria from
      their infected surroundings. Polymer brush-coatings attract low numbers of
      bacteria, but the virtue of polymer brush-coatings in vivo has seldom been
      investigated. Here, we determine the possible benefits of polymer brush-coated
      versus pristine silicone rubber in revision surgery, using a murine model.
      METHODS: BAI was induced in 26 mice by subcutaneous implantation of silicone
      rubber discs with a biofilm of Staphylococcus aureus Xen29. During the
      development of BAI, half of the mice received rifampicin/vancomycin treatment.
      After 5 days, the infected discs were removed from all mice, and either a polymer
      brush-coated or pristine silicone rubber disc was re-implanted. Revision discs
      were explanted after 5 days, and the number of cfu cultured from the discs and
      the surrounding tissue was determined. RESULTS: None of the polymer brush-coated
      discs after antibiotic treatment appeared colonized by staphylococci, whereas 83%
      of the pristine silicone rubber discs were re-infected. Polymer brush-coated
      discs also showed reduced colonization rates in the absence of antibiotic
      treatment when compared with pristine silicone rubber discs. Tissue surrounding
      the discs was culture-positive in all cases. CONCLUSIONS: Polymer brush-coatings
      are less prone to re-infection than pristine silicone rubber when used in
      revision surgery, i.e. when implanted in a subcutaneous pocket infected by a
      staphylococcal BAI. Antibiotic pre-treatment during the development of BAI hardly
      had any effect in preventing the colonization of pristine silicone rubber.

PMID- 18812427
TI  - High acquisition and environmental contamination rates of CC17 ampicillin
      resistant Enterococcus faecium in a Dutch hospital.
AB  - BACKGROUND: Enterococcus faecium has rapidly emerged as a nosocomial pathogen
      worldwide, and the majority of these isolates belong to clonal complex-17 (CC17).
      In Europe, CC17 isolates are usually ampicillin-resistant, but most are still
      vancomycin-sensitive. We aimed to study ampicillin-resistant E. faecium (ARE)
      epidemiology in our hospital. METHODS: In a 3 month study, 210 of 358 admissions
      (59%) to haematology and gastroenterology/nephrology were screened for rectal ARE
      colonization on admission (<48 h) and 148 of 210 (70%) also at discharge (<72 h).
      In a second (3 month) study, environmental swabs from eight predetermined sites
      were obtained from ARE-colonized haematology patients once weekly. All ARE
      isolates were genotyped by multiple-locus variable-number tandem repeat analysis
      (MLVA). RESULTS: ARE admission prevalence was 10% and 16% and acquisition rates
      were 39% and 15% in haematology and gastroenterology/nephrology, respectively.
      Carriage on admission was associated with previous admission <1 year (OR 5.0, 95%
      CI 1.8-14.0) and acquisition with beta-lactam (OR 2.7, 95% CI 1.1-6.7) and
      quinolone use (OR 3.1, 95% CI 1.1-8.2). Five of the 57 (9%) colonized patients
      developed invasive ARE infections. Genotyping revealed 12 genotypes (all CC17)
      with two MLVA types responsible for 94% of acquisitions. In 18 of the 19
      colonized patients, the environment was contaminated with ARE. Sites most often
      contaminated were the toilet seat (43%), over-bed table (34%) and television
      remote control (28%). CONCLUSIONS: CC17 ARE epidemiology is characterized by high
      admission (10% to 16%), acquisition (15% to 39%) and environmental contamination
      (22%) rates, resulting from cross-transmission, readmission and antibiotic
      pressure. A multifaceted infection control approach will be needed to curtail
      further spread.

PMID- 18812428
TI  - Paraneoplastic scleroderma secondary to hairy cell leukaemia successfully treated
      with cladribine.

PMID- 18812429
TI  - Ankylosing spondylitis and pulmonary sarcoidosis--a case report and discussion of
      the literature.

PMID- 18812430
TI  - Variation of immunological response in methotrexate-induced pneumonitis.
AB  - OBJECTIVES: To assess the variation of peripheral blood and bronchoalveolar
      lavage (BAL) inflammatory cell counts and lung biopsy findings with the degree of
      exposure to MTX therapy. METHODS: Fifty-six (16 males; 40 females) reported cases
      of MTX-induced pneumonitis (MTX-P) on low-dose MTX (5-30 mg) were identified from
      a literature search and classified using Searles and McKendry's criteria. The
      median cumulative dose was 300 mg and this was used to categorize patients into
      low and high MTX-exposure groups and 6 months was used to divide patients into
      early- and late-onset MTX-P groups. RESULTS: Neutrophil counts in the peripheral
      blood and BAL were significantly raised in the low MTX-exposure group compared
      with the high MTX-exposure group (P = 0.018 and 0.038, respectively). There were
      similar findings when early-onset was compared with late-onset group. Lymphocytes
      in BAL were significantly higher in the high MTX-exposure group compared with low
      dose cumulative group (P = 0.007). There were 6 (11%) recorded deaths and all
      were in the low MTX-exposure group. Early-onset/low MTX-exposure groups had a
      high prevalence of lung fibrosis. CONCLUSIONS: This is the first study to
      describe the variation of immunological responses in MTX-P with the degree of
      exposure to MTX. Our findings suggest that MTX-P can be divided into two groups:
      type 1 MTX-P that occurs early, predominated by neutrophils, lung fibrosis and
      has a high mortality; and type 2 MTX-P that occurs late, predominated by
      lymphocytes, has less lung fibrosis and low mortality.

PMID- 18812431
TI  - Design for the everest randomized trial of cortical stimulation and
      rehabilitation for arm function following stroke.
AB  - BACKGROUND: Cortical stimulation (CS) combined with rehabilitation may improve
      upper limb motor function after stroke. OBJECTIVE: Describe the study design for
      the Everest Clinical Trial, a randomized single-blinded pivotal device trial,
      testing safety and efficacy of epidural CS delivered during rehabilitation for
      upper limb motor function in patients with ischemic stroke. METHOD: A total of
      174 participants from 21 centers with hemiplegia at least 4 months after acute
      ischemic stroke are randomized in a 2:1 ratio to investigational or control
      groups. Investigational patients undergo implantation of cortical electrode and
      pulse generator and receive 6 weeks of upper limb rehabilitation with
      subthreshold CS delivered only during therapy. Control group patients receive the
      same therapy without device implantation or stimulation. Primary outcome measures
      include the upper extremity Fugl-Meyer (UEFM) score and the arm motor ability
      test (AMAT) measured at baseline and 1, 4, 12, and 24 weeks following
      rehabilitation treatment with primary endpoint at 4 weeks following treatment. A
      successful outcome is defined as an improvement in UEFM of at least 4.5 points
      and in AMAT of at least 0.21 points from baseline to primary endpoint. A 20%
      better success rate between investigational and control groups will be considered
      clinically meaningful. Adverse events occurring during the study will be
      identified. RESULTS: Not applicable. CONCLUSIONS: The Everest Clinical Trial is
      the first randomized pivotal trial on the safety and efficacy of direct CS
      delivered during rehabilitation for recovery of upper limb motor function in
      patients with ischemic stroke.

PMID- 18812432
TI  - A novel functional electrical stimulation treatment for recovery of hand function
      in hemiplegia: 12-week pilot study.
AB  - BACKGROUND: Loss of finger extension is common after stroke and can severely
      limit hand function. Contralaterally controlled functional electrical stimulation
      (CCFES) is a new treatment aimed at restoring volitional finger and thumb
      extension. A previous pilot study showed reductions in hand impairment after 6
      weeks of CCFES, but the effect did not persist after end of treatment. OBJECTIVE:
      This study aimed to evaluate the feasibility of achieving greater and more
      persistent gains with CCFES by increasing the treatment period to 12 weeks.
      METHODS: CCFES uses neuromuscular electrical stimulation to open the paretic hand
      in direct proportion to the degree of volitional opening of the unimpaired
      contralateral hand, which is detected by an instrumented glove. Three subjects
      with chronic hemiplegia participated in a 12-week CCFES treatment, which
      consisted of daily CCFES-assisted active repetitive hand-opening exercises and
      twice weekly functional task practice with CCFES. RESULTS: Maximum voluntary
      finger extension increased by 101 degrees and 68 degrees for subjects 1 and 2,
      respectively, but subject 3 had no improvement in finger extension. Box and Block
      score increased by 6, 15, and 7 blocks, and upper extremity Fugl-Meyer score
      increased by 11, 15, and 7 points for subjects 1, 2, and 3, respectively. The
      finger extension gains declined at the 1-month and 3-month follow-up for subjects
      1 and 2, but the gains in Box and Block and Fugl-Meyer scores persisted at follow
      up. CONCLUSIONS: Greater reductions in hand impairment were achieved by extending
      the treatment period. The effect and its longevity may be related to baseline
      impairment level.

PMID- 18812433
TI  - Effects of trunk restraint combined with intensive task practice on poststroke
      upper extremity reach and function: a pilot study.
AB  - BACKGROUND: Poststroke reaching is characterized by excessive trunk motion and
      abnormal shoulder-elbow coordination. Little attention is typically given to arm
      trunk kinematics during task practice. Preventing compensatory trunk motion
      during short-term practice immediately improves kinematics, but effects of longer
      term practice are unknown. OBJECTIVE: This study compared the effects of
      intensive task practice with and without trunk restraint on poststroke reaching
      kinematics and function. METHODS: A total of 11 individuals with chronic stroke,
      baseline Fugl-Meyer Upper Extremity Assessment scores 26 to 54, were randomized
      to 2 constraint-therapy intervention groups. All participants wore a mitt on the
      unaffected hand for 90% of waking hours over 14 days and participated in 10
      days/6 hours/day of supervised progressive task practice. During supervised
      sessions, one group trained with a trunk restraint (preventing anterior trunk
      motion) and one group did not. Tasks for the trunk-restraint group were located
      to afford repeated use of a shoulder flexion-elbow extension reaching pattern.
      Outcome measures included kinematics of unrestrained targeted reaching and tests
      of functional arm ability. RESULTS: Posttraining, the trunk-restraint group
      demonstrated straighter reach trajectories (P=.000) and less trunk displacement
      (P=.001). The trunk-restraint group gained shoulder flexion (P=.006) and elbow
      extension (P=.022) voluntary ranges of motion, the nonrestraint group did not.
      Posttraining angle-angle plots illustrated that individuals from the trunk
      restraint group transitioned from elbow flexion to elbow extension during mid
      reach; individuals in the nonrestraint group retained pretraining movement
      strategies. Both groups gained functional arm ability (P<.05 all tests).
      CONCLUSION: Intensive task practice structured to prevent compensatory trunk
      movements and promote shoulder flexion-elbow extension coordination may reinforce
      development of "normal" reaching kinematics.

PMID- 18812434
TI  - Lateral trunk displacement and stability during sit-to-stand transfer in relation
      to foot placement in patients with hemiparesis.
AB  - BACKGROUND: In hemiparetic individuals, sit-to-stand (STS) transfer is
      characterized by asymmetric weight-bearing and altered trunk kinematics that can
      be improved by positioning the affected foot behind the nonaffected one.
      OBJECTIVE: To examine the influence of frontal trunk kinematics on medio-lateral
      displacements of the center of pressure (CP) during STS performed with the feet
      placed in 2 different positions, as well as relationships between these
      parameters, medio-lateral stability, and clinical scores of the participants.
      METHODS: Eighteen patients with chronic stroke and 15 control individuals were
      evaluated during sit-to-stand transfers either in spontaneous foot position or
      with their affected or dominant foot placed behind, respectively. Medio-lateral
      CP, pelvis, and shoulder displacement were analyzed using 3D kinematic and
      kinetic data recordings of the whole task. Motor and sensory impairment,
      spasticity, muscle strength, and equilibrium were evaluated by standard scales.
      The possible time during which a participant could prevent a fall (minimal time
      to-contact) was used as a stability index. RESULTS: Spontaneously, the deviation
      of the CP of stroke participants paralleled the tilt of the trunk toward the
      nonaffected side, as early as the first third of the task. With the affected foot
      placed behind, trunk position did not differ from those of control participants
      who executed the transfer spontaneously. Hemiparetic participants were less
      stable than control participants. Placement of the feet had no significant effect
      on the stability of either group. Stability was strongly associated with better
      motor scores on the Chedoke-McMaster Stroke Assessment. CONCLUSIONS: In
      hemiparetic individuals, improving STS symmetry by positioning the affected foot
      behind the nonaffected one did not decrease medio-lateral stability, which was
      associated with the level of stroke-related motor impairments.

PMID- 18812435
TI  - Smoking prevalence in a north-west town following the introduction of Smoke-free
      England.
AB  - BACKGROUND: In July 2007, legislation banning smoking in public places was
      introduced in England. This study investigates the impact of this legislation on
      smoking in Bury. METHODS: A postal survey was undertaken before the
      implementation of the legislation. The survey was repeated 3 months after the
      smoking ban. Smoking prevalence was then compared. Participants were randomly
      selected using the PCT database of people registered with general practitioners.
      In the baseline and second survey, 3500 questionnaires were sent to participants.
      In the baseline survey 59.5% responded. In the second survey 56.3% responded.
      RESULTS: Results were standardized to age and gender bands from Bury's
      population. The baseline survey found that the standardized prevalence of smoking
      before the ban was 22.4% and after it was 22.6%. The proportion of smokers
      reporting that on average they smoked 20 cigarettes a day or greater fell from
      27.6 to 21.8% (P = 0.044). CONCLUSIONS: The study found that in Bury the smoking
      ban did not have a substantial impact on smoking prevalence but had an impact on
      the proportion of heavy smokers. The measurement of smoking prevalence before the
      change in legislation can be used to assess its long-term impact on smoking
      habits in Bury.

PMID- 18812436
TI  - Estimated prevalence and predictors of vitamin C deficiency within UK's low
      income population.
AB  - BACKGROUND: Recent case reports of scurvy indicate that vitamin C deficiency may
      be more prevalent that generally assumed. The Low Income Diet and Nutrition
      Survey (2003-05) of a representative sample of the low-income/materially deprived
      UK population included a plasma vitamin C measurement. METHODS: Adults aged
      >or=19 years from all countries/regions of UK were screened to identify low
      income/materially deprived households. A valid plasma vitamin C measurement was
      made in 433 men and 876 women. The results were weighted for sampling probability
      and non-response. RESULTS: An estimated 25% of men and 16% of women in the low
      income/materially deprived population had plasma vitamin C concentrations
      indicative of deficiency (<11 micromol l(-1)), and a further fifth of the
      population had levels in the depleted range (11-28 micromol l(-1)). Being a man,
      reporting low-dietary vitamin C intake, not taking vitamin supplements and
      smoking were predictors of plasma vitamin C levels <or=28 micromol l(-1) in
      mutually adjusted logistic regression models. CONCLUSION: Health professionals
      need to be aware that poor vitamin C status is relatively common among adults
      living on a low income.

PMID- 18812437
TI  - A bioinformatics tool for linking gene expression profiling results with public
      databases of microRNA target predictions.
AB  - MicroRNAs are short (approximately 22 nucleotides) noncoding RNAs that regulate
      the stability and translation of mRNA targets. A number of computational
      algorithms have been developed to help predict which microRNAs are likely to
      regulate which genes. Gene expression profiling of biological systems where
      microRNAs might be active can yield hundreds of differentially expressed genes.
      The commonly used public microRNA target prediction databases facilitate gene-by
      gene searches. However, integration of microRNA-mRNA target predictions with gene
      expression data on a large scale using these databases is currently cumbersome
      and time consuming for many researchers. We have developed a desktop software
      application which, for a given target prediction database, retrieves all
      microRNA:mRNA functional pairs represented by an experimentally derived set of
      genes. Furthermore, for each microRNA, the software computes an enrichment
      statistic for overrepresentation of predicted targets within the gene set, which
      could help to implicate roles for specific microRNAs and microRNA-regulated genes
      in the system under study. Currently, the software supports searching of results
      from PicTar, TargetScan, and miRanda algorithms. In addition, the software can
      accept any user-defined set of gene-to-class associations for searching, which
      can include the results of other target prediction algorithms, as well as gene
      annotation or gene-to-pathway associations. A search (using our software) of
      genes transcriptionally regulated in vitro by estrogen in breast cancer uncovered
      numerous targeting associations for specific microRNAs-above what could be
      observed in randomly generated gene lists-suggesting a role for microRNAs in
      mediating the estrogen response. The software and Excel VBA source code are
      freely available at http://sigterms.sourceforge.net.

PMID- 18812438
TI  - Crystal structure of Escherichia coli PNPase: central channel residues are
      involved in processive RNA degradation.
AB  - Bacterial polynucleotide phosphorylase (PNPase) plays a major role in mRNA
      turnover by the degradation of RNA from the 3'- to 5'-ends. Here, we determined
      the crystal structures of the wild-type and a C-terminal KH/S1 domain-truncated
      mutant (DeltaKH/S1) of Escherichia coli PNPase at resolutions of 2.6 A and 2.8 A,
      respectively. The six RNase PH domains of the trimeric PNPase assemble into a
      ring-like structure containing a central channel. The truncated mutant DeltaKH/S1
      bound and cleaved RNA less efficiently with an eightfold reduced binding
      affinity. Thermal melting and acid-induced trimer dissociation studies, analyzed
      by circular dichroism and dynamic light scattering, further showed that
      DeltaKH/S1 formed a less stable trimer than the full-length PNPase. The crystal
      structure of DeltaKH/S1 is more expanded, containing a slightly wider central
      channel than that of the wild-type PNPase, suggesting that the KH/S1 domain helps
      PNPase to assemble into a more compact trimer, and it regulates the channel size
      allosterically. Moreover, site-directed mutagenesis of several arginine residues
      in the channel neck regions produced defective PNPases that either bound and
      cleaved RNA less efficiently or generated longer cleaved oligonucleotide
      products, indicating that these arginines were involved in RNA binding and
      processive degradation. Taking these results together, we conclude that the
      constricted central channel and the basic-charged residues in the channel necks
      of PNPase play crucial roles in trapping RNA for processive exonucleolytic
      degradation.

PMID- 18812439
TI  - MicroRNA miR-21 overexpression in human breast cancer is associated with advanced
      clinical stage, lymph node metastasis and patient poor prognosis.
AB  - To investigate the global expression profile of miRNAs in primary breast cancer
      (BC) and normal adjacent tumor tissues (NATs) and its potential relevance to
      clinicopathological characteristics and patient survival, the genome-wide
      expression profiling of miRNAs in BC was investigated using a microarray
      containing 435 mature human miRNA oligonucleotide probes. Nine miRNAs of hsa-miR
      21, hsa-miR-365, hsa-miR-181b, hsa-let-7f, hsa-miR-155, hsa-miR-29b, hsa-miR
      181d, hsa-miR-98, and hsa-miR-29c were observed to be up-regulated greater than
      twofold in BC compared with NAT, whereas seven miRNAs of hsa-miR-497, hsa-miR-31,
      hsa-miR-355, hsa-miR-320, rno-mir-140, hsa-miR-127 and hsa-miR-30a-3p were
      observed to be down-regulated greater than twofold. The most significantly up
      regulated miRNAs, hsa-mir-21 (miR-21), was quantitatively analyzed by TaqMan real
      time PCR in 113 BC tumors. Interestingly, among the 113 BC cases, high level
      expression of miR-21 was significantly correlated with advanced clinical stage (P
      = 0.006, Fisher's exact text), lymph node metastasis (P = 0.007, Fisher's exact
      text), and shortened survival of the patients (hazard ratio [HR]=5.476, P <
      0.001). Multivariate Cox regression analysis revealed this prognostic impact
      (HR=4.133, P = 0.001) to be independent of disease stage (HR=2.226, P = 0.013)
      and histological grade (HR=3.681, P = 0.033). This study could identify the
      differentiated miRNAs expression profile in BC and reveal that miR-21
      overexpression was correlated with specific breast cancer biopathologic features,
      such as advanced tumor stage, lymph node metastasis, and poor survival of the
      patients, indicating that miR-21 may serve as a molecular prognostic marker for
      BC and disease progression.

PMID- 18812440
TI  - Chronic kidney disease, hypertension and silent brain infarction.

PMID- 18812441
TI  - Vocal cord paresis and diaphragmatic dysfunction are severe and frequent symptoms
      of GDAP1-associated neuropathy.
AB  - Cranial nerve involvement in Charcot-Marie-Tooth disease (CMT) is rare, though
      there are a number of CMT syndromes in which vocal cord paralysis is a
      characteristic feature. CMT disease due to mutations in the ganglioside-induced
      differentiation-associated protein 1 gene (GDAP1) has been reported to be
      associated with vocal cord and diaphragmatic palsy. In order to address the
      prevalence of these complications in patients with GDAP1 mutations we evaluated
      vocal cord and respiratory function in nine patients from eight unrelated
      families with this disorder. Hoarseness of the voice and inability to speak
      loudly were reported by eight patients and one had associated symptoms of
      respiratory insufficiency. Patients were investigated by means of peripheral and
      phrenic nerve conduction studies, flexible laryngoscopy, pulmonary function
      studies and polysomnography. Nerve conduction velocities and pathological studies
      were compatible with axonal CMT (CMT2). Flexible laryngoscopy showed left vocal
      cord palsy in four cases, bilateral cord palsies in four cases and was normal in
      one case. Restrictive respiratory dysfunction was seen in the eight patients with
      vocal cord paresis who were all chair-bound. These eight had confirmed phrenic
      nerve dysfunction on neurophysiology evaluation. The patient with normal vocal
      cord and pulmonary function had a less severe clinical course.This study shows
      that CMT patients with GDAP1 mutations develop severe disability due to weakness
      of limb muscles and that laryngeal and respiratory muscle involvement occurs late
      in the disease process when significant proximal upper limb weakness has
      developed. The early and predominant involvement of the left vocal cord
      innervated by the longer left recurrent laryngeal nerve suggests a length
      dependent pattern of nerve degeneration. In GDAP1 neuropathy, respiratory
      function should be thoroughly investigated because life expectancy can be
      compromised due to respiratory failure.

PMID- 18812442
TI  - The role of motor intention in motor awareness: an experimental study on
      anosognosia for hemiplegia.
AB  - Recent theories propose that anosognosia for hemiplegia (AHP) results from
      specific impairments in motor planning. However, no study has hitherto directly
      investigated the role of motor intention in the observed non-veridical awareness
      of action in AHP. We developed the following paradigm to investigate the role of
      motor planning in awareness in patients with AHP: Four hemiplegic patients with
      and four without anosognosia were provided with false visual feedback of movement
      in their left paralysed arm through a prosthetic rubber hand. We examined whether
      the ability to detect presence or absence of movement based on visual evidence
      varied according to whether the patient had planned to move their limb or not.
      Motor intention had a selective effect on patients with AHP; they were more
      likely than controls (U = 16, P < 0.001) to ignore the visual feedback of a
      motionless hand and claim that they moved it when they had the intention to do so
      (self-generated movement) than when they expected an experimenter to move their
      own hand (externally generated movement), or there was no expectation of
      movement. By contrast, patients without AHP were not influenced by these
      manipulations, and did not claim they moved their hand when the hand remained
      still. This is the first direct demonstration that altered awareness of action in
      AHP reflects a dominance of motor intention prior to action over sensory
      information about the actual effects of movement.

PMID- 18812443
TI  - Small focal cortical dysplasia lesions are located at the bottom of a deep
      sulcus.
AB  - Focal cortical dysplasia (FCD) is often characterized by minor structural changes
      that may go unrecognized by standard radiological analysis. Visual assessment of
      morphological characteristics of FCD and sulci harbouring them is difficult due
      to the complexity of brain convolutions. Our purpose was to elucidate and
      quantify the spatial relationship between FCD lesions and brain sulci using
      automated sulcal extraction and morphometry. We studied 43 consecutive FCD
      patients using high-resolution MRI. Lesions were classified into small and large
      using qualitative (detection on initial clinical assessment of conventional MRI)
      and quantitative (volume) criteria. Sulci were identified and labelled
      automatically using an algorithm based on a congregation of neural networks.
      Segmented FCD lesions and sulci were then simultaneously visualized in 3D. We
      measured mean and maximum depth of sulci related to each FCD and of the
      corresponding sulci in 21 healthy controls. In addition, we calculated sulcal
      depth within the FCD neighbourhood. Twenty-one (21/43 = 49%) patients had small
      FCD lesions (volume range: 128-3093 mm(3)). Among them, 17 (81%) had been
      overlooked during initial radiological evaluation and were subsequently
      identified using image processing. Eighteen (18/21 = 86%) small FCD lesions were
      located at the bottom of a sulcus. Two others were related to the walls of two
      sulci and one was located at the crown of a gyrus. Mean and maximum depth of
      sulci related to the FCD was higher than that of the corresponding sulci in
      controls (P < 0.008). Sulcal depth within lesional neighbourhood had larger mean
      depth than that of the entire sulcus (P < 0.0002). Evidence that small FCD
      lesions are preferentially located at the bottom of an abnormally deep sulcus may
      be used to direct the search for developmental abnormalities, particularly in
      patients in whom large-scale MRI features are only mildly abnormal or absent.

PMID- 18812444
TI  - Conditions associated with an abnormal nonspecific pattern of pulmonary function
      tests.
AB  - BACKGROUND: Little is known about a fairly frequent abnormal pattern of pulmonary
      function test results: reduced FEV(1) and FVC with a normal FEV(1)/FVC and normal
      total lung capacity. We term this a nonspecific pattern (NSP). We sought to
      identify medical conditions having this pattern and to explore mechanisms
      producing it. METHODS: From a database of 80,929 test results, the NSP was found
      in 7,702 subjects from whom was drawn a random sample of 100 subjects. Medical
      records and all available tests were examined. RESULTS: Airway
      hyperresponsiveness (AHR) and obesity were common. Two groups of subjects were
      identified. Group A consisted of 68 subjects with evidence of airway disease,
      including AHR and chronic lung disease. A volume derecruitment model was proposed
      to explain their NSP. Group B consisted of 32 subjects with no evidence of airway
      disease. Restricted expansion of the thorax or lung may explain the NSP in most
      of these subjects. Forty subjects had repeated tests, and in only 17 were the
      test results consistently nonspecific. CONCLUSIONS: In a random sample of 100
      subjects with the NSP, the probable underlying cause of the pattern in 68
      subjects was airway disease. In most of the remaining 32 subjects, restricted
      expansion of the thorax or lung may be implicated.

PMID- 18812445
TI  - Ambrisentan therapy in patients with pulmonary arterial hypertension who
      discontinued bosentan or sitaxsentan due to liver function test abnormalities.
AB  - BACKGROUND: Some endothelin receptor antagonists (ERAs) are associated with liver
      function test (LFT) result abnormalities. However, ambrisentan has an incidence
      of serum aminotransferase levels more than three times the upper limit of normal
      (ULN), similar to that observed in PAH patients who are not receiving ERAs.
      Because ambrisentan may provide benefits in PAH patients who have discontinued
      ERA therapy due to LFT abnormalities, we evaluated the safety and efficacy of
      ambrisentan in this patient population. METHODS: Patients who previously
      discontinued bosentan and/or sitaxsentan due to LFT abnormalities received
      ambrisentan, 2.5 mg qd, for 4 weeks followed by 5 mg/d for 8 weeks. The primary
      end point was the incidence of aminotransferase levels more than three times ULN
      considered by the investigator to be related to ambrisentan and resulting in drug
      discontinuation. Secondary end points included aminotransferase levels more than
      five times ULN requiring drug discontinuation and more than three times ULN
      requiring dose reduction, as well as changes in 6-min walk distance (6MWD), Borg
      dyspnea index, World Health Organization functional class, and Short Form-36
      health survey score. Patients continued treatment beyond the 12-week end point
      with monthly monitoring of LFTs. RESULTS: Thirty-six patients who previously
      discontinued bosentan (n = 31), sitaxsentan (n = 2), or both (n = 3) were
      enrolled. At baseline, 69.4% of patients were receiving prostanoid and/or
      sildenafil therapy. No patient had an aminotransferase level more than three
      times ULN that required ambrisentan discontinuation. One patient had a transient
      aminotransferase level more than three times ULN that resolved following a
      temporary dose reduction. No additional aminotransferase levels more than three
      times ULN were observed with long-term treatment (median exposure, 102 weeks),
      despite dose increases to 10 mg qd in more than half of the patients. Significant
      improvements in 6MWD and other efficacy assessments were observed. CONCLUSIONS:
      Ambrisentan treatment may be an option for patients who have discontinued
      bosentan and/or sitaxsentan therapy due to LFT result abnormalities. TRIAL
      REGISTRATION: Clinicaltrials.gov Identifier NCT00423592.

PMID- 18812446
TI  - Endobronchial ultrasonography-guided transbronchial needle aspiration increases
      the diagnostic yield of peripheral pulmonary lesions: a randomized trial.
AB  - BACKGROUND: The diagnostic yield of endobronchial ultrasonography (EBUS)-guided
      transbronchial needle aspiration (TBNA) for peripheral pulmonary lesions (PPLs)
      has not been evaluated. The diagnostic impact of TBNA when the EBUS probe is
      adjacent to lesions remains to be determined. DESIGN: A prospective, randomized
      trial. METHODS: Two hundred two patients with PPLs and positive EBUS findings
      were enrolled. They were randomly classified into two groups. In the EBUS
      conventional diagnostic procedures (CDPs) group (103 patients), both
      transbronchial biopsy (TBB) and bronchial washing (BW) were performed. In the
      EBUS-TBNA plus CDPs group (99 patients), TBNA, TBB, and BW were performed. The
      diagnostic yield in each group was compared. RESULTS: A total of 182 patients (94
      in the EBUS CDPs group and 88 in the EBUS-TBNA plus CDPs group) were analyzed.
      The yield in the EBUS-TBNA plus CDPs group (78.4%) was significantly higher than
      the EBUS CDPs group (60.6%, p = 0.015). Cases in which the EBUS probe was located
      within the lesions had a significantly higher diagnostic yield (78.3%) than when
      the EBUS probe was adjacent to them (47.2%, p < 0.001). Concerning the three
      different techniques, TBNA showed the highest diagnostic yield (62.5%) in
      comparison to TBB (48.9%) and to BW (19.8%). The diagnostic yield of TBNA
      remained unchanged even when the EBUS probe was adjacent to the lesions (p =
      0.89). No additional adverse effects were observed in the EBUS-TBNA plus CDPs
      group. CONCLUSIONS: Applying TBNA to EBUS-guided CDPs further increased the
      diagnostic yield of PPLs without additional risk. The diagnostic advantage of
      TBNA became more obvious if the EBUS probe was adjacent to the lesions. TRIAL
      REGISTRATION: Clinicaltrials.gov Identifier: NCT00626587.

PMID- 18812447
TI  - Estimating a minimally important difference in pulmonary arterial hypertension
      following treatment with sildenafil.
AB  - BACKGROUND: No guidelines exist to help physicians determine whether functional
      and health-related quality of life (HRQoL) changes observed following treatment
      of patients with pulmonary arterial hypertension (PAH) represent important
      benefits. These analyses were undertaken to help define a minimally important
      difference (MID) in exercise capacity, measured by the 6-min walk distance
      (6MWD), and HRQoL, measured by the Short Form-36 (SF-36) questionnaire in
      patients with PAH. PATIENTS AND METHODS: Data from a 12-week sildenafil study in
      patients with PAH were used to calculate MIDs for 6MWD and the SF-36 physical
      functioning, role-physical, social functioning, and vitality scales using effect
      size, SEM, and SE of the difference approaches. Data from all patients enrolled
      into the treatment groups in the study were included. RESULTS: A range of
      plausible MID estimates, including a score change for SF-36 scales and a change
      in distance walked in meters for 6MWD, were generated for each end point. Mean
      values were calculated for each outcome and recommended as MIDs for each
      parameter. Based on these computations, the mean MIDs for the SF-36 physical
      functioning, role-physical, social functioning, and vitality scales and for 6MWD
      were 13, 25, 21, and 15 points, and 41 m, respectively. CONCLUSIONS: This is the
      first clinical investigation to estimate MIDs for key SF-36 domains and 6MWD in
      patients with PAH and provides a much needed metric for interpreting the level of
      change in patients with PAH against which other treatments and trials can be
      measured.

PMID- 18812448
TI  - A method to derive lower limit of normal for the FEV1/forced expiratory volume at
      6 s of exhalation ratio from FEV1/FVC data.
AB  - BACKGROUND: The FEV(1)/forced expiratory volume at 6 s of exhalation (FEV(6))
      ratio has been suggested as a surrogate for the FEV(1)/FVC ratio to detect airway
      obstruction. Current guidelines require that lower limit of normal (LLN) values
      be implemented to detect an abnormality. In most populations, LLN equations are
      available for the FEV(1)/FVC ratio but not for the FEV(1)/FEV(6) ratio. We
      propose a simplified statistical method to approximate reasonably the
      FEV(1)/FEV(6) LLN in a population for which FEV(1)/FVC LLN values are already
      available. METHODS: Spirometric data were collected from 8,273 European patients
      aged 20 to 85 years. We computed by receiver operator characteristics analysis
      the best-fit cutoff FEV(1)/FEV(6) ratio distributions in function of age and sex
      for obstruction as diagnosed from FEV(1)/FVC LLN values obtained from the
      relevant reference equations for subjects aged 20 to 70 and 65 to 85 years. We
      compared the diagnosis of obstruction obtained from these surrogate equations
      against the reference diagnosis made by FEV(1)/FVC LLN. RESULTS: Misdiagnoses
      from the surrogate equations (FEV(1)/FEV(6) = 75.58 - 0.11 x age for men, and
      77.70 - 0.09 x age for women aged 20 to 70 years) were all within 2.3 +/- 2.0% of
      the reference LLN. Similar results were found in the group aged 65 to 85 years.
      CONCLUSIONS: The study confirms the feasibility of computing a surrogate LLN
      equation for the FEV(1)/FEV(6) ratio in a population for which the accepted
      FEV(1)/FVC LLN already exists. Surrogate equations for FEV(1)/FEV(6) ratio may
      extend its use for screening and case finding when simplified spirometry is
      needed.

PMID- 18812449
TI  - The effects of flexible bronchoscopy on mechanical ventilation in a pediatric
      lung model.
AB  - BACKGROUND: Flexible bronchoscopy performed through endotracheal tubes (ETTs) in
      children receiving mechanical ventilation can significantly impact ventilation,
      but the magnitude of this impact has not been established. We used a lung model
      to simulate mechanical ventilation in a range of child sizes in order to
      determine how the insertion of pediatric flexible bronchoscopes into ETTs alters
      ventilatory parameters, especially tidal volume (Vt) and peak inspiratory
      pressure (PIP), in both healthy and diseased lungs. METHODS: We simulated five
      child sizes based on weight, and evaluated 22 bronchoscope/ETT combinations,
      first in pressure control (PC) ventilation mode and then in volume control (VC)
      ventilation mode. The combinations ranged from the 2.2-mm (bronchoscope outer
      diameter)/3.0-mm (ETT inner diameter) to 5.0-mm bronchoscope/8.0-mm ETT. The
      primary outcome measures were decrease in Vt after bronchoscope insertion during
      PC ventilation and increase in PIP during VC ventilation. RESULTS: In the PC
      ventilator mode, Vt decreased by > 50% with nine of the combinations, while
      during VC ventilation, PIP increased by >or= 20 cm H(2)O with seven combinations.
      The 2.2-mm bronchoscope/3.0-mm ETT, 2.8-mm bronchoscope/5.0-mm ETT, and 3.6-mm
      bronchoscope/5.0-mm ETT combinations severely impaired ventilation, while the 3.6
      mm bronchoscope/4.5-mm ETT, 5.0-mm bronchoscope/6.5-mm ETT, and 5.0-mm
      bronchoscope/7.0-mm ETT combinations were incompatible with adequate ventilation.
      CONCLUSIONS: The insertion of bronchoscopes into ETTs can lead to clinically
      relevant decreases in Vt when in the PC ventilator mode and large increases in
      PIP during VC ventilation. The minimum bronchoscope/ETT diameter difference
      required to maintain adequate ventilation increases with child size.

PMID- 18812450
TI  - A new diagnostic score for occupational asthma: the area between the curves (ABC
      score) of peak expiratory flow on days at and away from work.
AB  - BACKGROUND: Evidence-based guidelines recommend serial measurements of peak
      expiratory flow (PEF) on days at and away from work as the first step in the
      objective confirmation of occupational asthma. The aim of this study was to
      improve the diagnostic value of computer-based PEF analysis by using the program
      Oasys-2 to calculate a score from the area between the curves (ABC) of PEF on
      days at and away from work. METHODS: Mean 2-hourly PEFs were plotted separately
      for workdays and rest days for 109 workers with occupational asthma and 117
      control asthmatics. A score based on the ABC was computed from records containing
      >or= 4 day shifts, >or= 4 rest days, and >or= 6 readings per day. Patients were
      randomly classified into two data sets (analysis and test sets). Receiver
      operator characteristic (ROC) curve analysis determined a cutoff point from set 1
      that best identified those with occupational asthma, which was then tested in set
      2. RESULTS: Logistic regression analysis showed that all ABC PEF scores were
      significant predictors of occupational asthma, with the best being ABC per hour
      from waking (odds ratio, 11.9 per 10 L/h/min; 95% confidence interval, 10.8 to
      13.1). ROC curve analysis showed that a difference of 15 L/min/h provided a high
      specificity without compromising sensitivity in diagnosing occupational asthma.
      Analysis of data set 2 confirmed a specificity of 100% and sensitivity of 72%.
      CONCLUSION: The ABC PEF score is sensitive and specific for the diagnosis of
      occupational asthma and can be calculated from a shorter PEF surveillance than is
      needed for the current Oasys-2 work effect index.

PMID- 18812451
TI  - Effect of specific allergen inhalation on serum adiponectin in human asthma.
AB  - BACKGROUND: Adiponectin is associated with asthma. The direction of this
      association is not known in humans. In mice, this association is bidirectional:
      allergen inhalation affects serum adiponectin, and exogenous adiponectin
      administration affects asthma. We sought to evaluate whether allergen inhalation
      affects serum adiponectin in human asthma. METHODS: This study included eight
      sensitized subjects with mild asthma and six healthy control subjects. Asthmatic
      subjects were challenged with inhaled specific allergen (positive allergen skin
      test), methacholine, and irrelevant allergen (negative allergen skin test).
      Control subjects were challenged with irrelevant allergen. Sequential serum
      samples were obtained before and nine times after each challenge. Serum
      adiponectin- (primary outcome), leptin-, adiponectin-to-leptin ratio-, eotaxin-,
      and tumor necrosis factor-alpha-response curves, area under the curves, and
      baseline and peak concentrations were evaluated. Statistical analysis used
      repeated-measures analysis of variance and paired t tests. RESULTS: There were no
      significant differences in outcome measures among the challenges in asthmatic
      subjects or when compared to control subjects. Type II error is an unlikely
      explanation for these findings because the study was adequately powered to detect
      changes in serum adiponectin, as reported in the literature. Further, pooled data
      showed that serum adiponectin diurnal variation curves were lower in asthmatic
      subjects than in control subjects. CONCLUSIONS: Serum adiponectin concentrations
      are lower in asthmatic subjects than in control subjects. Specific allergen
      inhalation in asthmatic subjects does not acutely affect serum adiponectin
      concentrations. The reverse association (ie, effect of adiponectin on asthma)
      needs further study. If future studies prove adiponectin to be a protective
      factor for asthma, modulating adiponectin may open a new approach toward managing
      asthma.

PMID- 18812452
TI  - Ventilator-associated tracheobronchitis: the impact of targeted antibiotic
      therapy on patient outcomes.
AB  - Nosocomial lower respiratory tract infections are a common cause of morbidity and
      mortality in ICU patients receiving mechanical ventilation. Many studies have
      investigated the management and prevention of ventilator-associated pneumonia
      (VAP), but few have focused on the role of ventilator-associated
      tracheobronchitis (VAT). The pathogenesis of lower respiratory tract infections
      often begins with tracheal colonization that may progress to VAT, and in selected
      patients to VAP. Since there is no well-established definition of VAT,
      discrimination between VAT and VAP can be challenging. VAT is a localized disease
      with clinical signs (fever, leukocytosis, and purulent sputum), microbiologic
      information (Gram stain with bacteria and leukocytes, with either a positive
      semiquantitative or a quantitative sputum culture), and the absence of a new
      infiltrate on chest radiograph. Monitoring endotracheal aspirates has been used
      to identify and quantify pathogens colonizing the lower airway, to diagnose VAT
      or VAP, and to initiate early, targeted antibiotic therapy. Recent data suggest
      that VAT appears to be an important risk factor for VAP and that targeted
      antibiotic therapy for VAT may be a new paradigm for VAP prevention and better
      patient outcomes.

PMID- 18812453
TI  - Prevalence of pulmonary embolism in acute exacerbations of COPD: a systematic
      review and metaanalysis.
AB  - BACKGROUND: Nearly 30% of all exacerbations of COPD do not have a clear etiology.
      Although pulmonary embolism (PE) can exacerbate respiratory symptoms such as
      dyspnea and chest pain, and COPD patients are at a high risk for PE due to a
      variety of factors including limited mobility, inflammation, and comorbidities,
      the prevalence of PE during exacerbations is uncertain. METHODS: A systematic
      review of the literature was performed to determine the reported prevalence of PE
      in acute exacerbations of COPD in patients who did and did not require
      hospitalization. The literature search was performed using MEDLINE, CINAHL, and
      EMBASE, and complemented by hand searches of bibliographies. Only cross-sectional
      or prospective studies that used CT scanning or pulmonary angiography for PE
      diagnosis were included. RESULTS: Of the 2,407 articles identified, 5 met the
      inclusion criteria (sample size, 550 patients). Overall, the prevalence of PE was
      19.9% (95% confidence interval [CI], 6.7 to 33.0%; p = 0.014). In hospitalized
      patients, the prevalence was higher at 24.7% (95% CI, 17.9 to 31.4%; p = 0.001)
      than those who were evaluated in the emergency department (3.3%). Presenting
      symptoms and signs were similar between patients who did and did not have PE.
      CONCLUSIONS: One of four COPD patients who require hospitalization for an acute
      exacerbation may have PE. A diagnosis of PE should be considered in patients with
      exacerbation severe enough to warrant hospitalization, especially in those with
      an intermediate-to-high pretest probability of PE.

PMID- 18812454
TI  - The treatment of lupus pernio: results of 116 treatment courses in 54 patients.
AB  - BACKGROUND: Lupus pernio is a disfiguring sarcoidosis skin lesion that is
      difficult to treat and often causes a major psychosocial impact that may
      adversely affect the patient's quality of life. We reviewed the treatment outcome
      of 54 patients with lupus pernio who received 116 individual courses of treatment
      in our sarcoidosis clinic. METHODS: Lupus pernio patients were identified from an
      institution-approved database. All patients were assessed at each clinic visit
      with facial photographs. By examining the photographs, the percentage of face
      involved (< 10%, 10 to 25%, > 25 to 50%, > 50%) was determined as was the effect
      of therapy (resolution, near resolution, improvement, no change, worsening).
      Medications included infliximab-containing regimens; systemic corticosteroids;
      noninfliximab, noncorticosteroid agents; and corticosteroids plus
      noncorticosteroid agents. RESULTS: In terms of achieving resolution or near
      resolution, infliximab regimens were superior to all others (infliximab, 77%;
      corticosteroids plus noncorticosteroids, 29%; corticosteroids, 20%;
      noncorticosteroids, 11%; infliximab vs other therapies: corticosteroids plus
      noncorticosteroids, p = 0.0015; corticosteroids, p = 0.0005; noncorticosteroids,
      p = 0.0002). The percentage of facial involvement also improved most with
      infliximab. Evaluating a secondary analysis of achieving resolution, near
      resolution, or improvement, infliximab (92%) was superior to noncorticosteroids
      (20%; p < 0.0001) and corticosteroids plus noncorticosteroids (56%; p = 0.0098),
      but not corticosteroids (72%; p = 0.2456); and noncorticosteroid agents were
      inferior to all other regimens. CONCLUSIONS: Infliximab appears superior to
      systemic corticosteroids with or without additional agents for the treatment of
      lupus pernio. Noninfliximab, noncorticosteroid-containing regimens are of limited
      use for this condition.

PMID- 18812455
TI  - Rapid eye movement-related sleep-disordered breathing: influence of age and
      gender.
AB  - BACKGROUND: Sleep-disordered breathing (SDB) occurring during rapid eye movement
      (REM) sleep occurs more frequently in women than men. We sought to characterize
      REM SDB prevalence by gender and age to identify factors that could account for
      this discrepancy. METHODS: Subjects with REM SDB were identified among 2,486
      patients referred to a university sleep laboratory with an apnea-hypopnea index
      (AHI) >or= 5 events per hour. REM SDB was defined as non-REM (NREM) AHI <or= 15/h
      and REM AHI/NREM AHI ratio >or= 2. Regression analyses were utilized to determine
      factors associated with REM SDB. RESULTS: REM SDB prevalence was 40.8% in women
      and 21.0% in men. After adjusting for age and obesity, female sex remained a risk
      factor for REM SDB (odds ratio, 3.0; 95% confidence interval [CI], 1.8 to 4.2).
      REM SDB prevalence waned with increasing age in both sexes, such that the odds of
      having REM SDB fell by 26.7% (95% CI, 15.2 to 38.2%) per decade. REM AHI/NREM AHI
      decreased with age only in women, falling 10.9% (95% CI, 5.5 to 16.3%) per
      decade. NREM AHI in women increased the most with age (16.0%; 95% CI, 11.1 to
      20.9%) per decade, and least with body mass index (BMI) [13.0%; 9.1 to 16.9%] for
      every 5-unit BMI increase when compared to REM AHI for women and either index for
      men. CONCLUSIONS: REM SDB prevalence decreases with age in women as does REM
      AHI/NREM AHI, perhaps secondary to a disproportionate age-dependent rise in NREM
      vs REM AHI in women. Younger women may be protected from SDB during NREM sleep,
      even in the face of obesity. These patterns may reflect age-related decreases in
      female hormones.

PMID- 18812456
TI  - Transcriptomic analysis of PPARalpha-dependent alterations during cardiac
      hypertrophy.
AB  - Peroxisome proliferator-activated receptor (PPAR)alpha regulates lipid metabolism
      at the transcriptional level and modulates the expression of genes involved in
      inflammation, cell proliferation, and differentiation. Although PPARalpha has
      been shown to mitigate cardiac hypertrophy, knowledge about underlying mechanisms
      and the nature of signaling pathways involved is fragmentary and incomplete. The
      aim of this study was to identify the processes and signaling pathways regulated
      by PPARalpha in hearts challenged by a chronic pressure overload by means of
      whole genome transcriptomic analysis. PPARalpha-/- and wild-type mice were
      subjected to transverse aortic constriction (TAC) for 28 days, and left
      ventricular gene expression profile was determined with Affymetrix GeneChip Mouse
      Genome 430 2.0 arrays containing >45,000 probe sets. In unchallenged hearts, the
      mere lack of PPARalpha resulted in 821 differentially expressed genes, many of
      which are related to lipid metabolism and immune response. TAC resulted in a more
      pronounced cardiac hypertrophy and more extensive changes in gene expression
      (1,910 and 312 differentially expressed genes, respectively) in PPARalpha-/- mice
      than in wild-type mice. Many of the hypertrophy-related genes were related to
      development, signal transduction, actin filament organization, and collagen
      synthesis. Compared with wild-type hypertrophied hearts, PPARalpha-/-
      hypertrophied hearts revealed enrichment of gene clusters related to
      extracellular matrix remodeling, immune response, oxidative stress, and
      inflammatory signaling pathways. The present study therefore demonstrates that,
      in addition to lipid metabolism, PPARalpha is an important modulator of immune
      and inflammatory response in cardiac muscle.

PMID- 18812457
TI  - Hypothalamus transcriptome profile suggests an anorexia-cachexia syndrome in the
      anx/anx mouse model.
AB  - The anx/anx mouse displays poor appetite and lean appearance and is considered a
      good model for the study of anorexia nervosa. To identify new genes involved in
      feeding behavior and body weight regulation we performed an expression profiling
      in the hypothalamus of the anx/anx mice. Using commercial microarrays we detected
      156 differentially expressed genes and validated 92 of those using TaqMan low
      density arrays. The expression of a set of 87 candidate genes selected based on
      literature evidences was also quantified by TaqMan low-density arrays. Our
      results showed enrichment in deregulated genes involved in cell death, cell
      morphology, and cancer, as well as an alteration of several signaling circuits
      involved in energy balance including neuropeptide Y and melanocortin signaling.
      The expression profile along with the phenotype led us to conclude that anx/anx
      mice resemble the anorexia-cachexia syndrome typically observed in cancer,
      infection with human immunodeficiency virus or chronic diseases, rather than
      starvation, and that anx/anx mice could be considered a good model for the
      treatment and investigation of this condition.

PMID- 18812458
TI  - Mapping of quantitative trait loci for cholesterol, LDL, HDL, and triglyceride
      serum concentrations in pigs.
AB  - The fine mapping of polymorphisms influencing cholesterol (CT), triglyceride
      (TG), and lipoprotein serum levels in human and mouse has provided a wealth of
      knowledge about the complex genetic architecture of these traits. The extension
      of these genetic analyses to pigs would be of utmost importance since they
      constitute a valuable biological and clinical model for the study of coronary
      artery disease and myocardial infarction. In the present work, we performed a
      whole genome scan for serum lipid traits in a half-sib Duroc pig population of
      350 individuals. Phenotypic registers included total CT, TG, and low (LDL)- and
      high (HDL)-density lipoprotein serum concentrations at 45 and 190 days of age.
      This approach allowed us to identify two genomewide significant quantitative
      trait loci (QTL) for HDL-to-LDL ratio at 45 days (SSC6, 84 cM) and for TG at 190
      days (SSC4, 23 cM) as well as a number of chromosomewide significant QTL. The
      comparison of QTL locations at 45 and 190 days revealed a notable lack of
      concordance at these two time points, suggesting that the effects of these QTL
      are age specific. Moreover, we have observed a considerable level of
      correspondence among the locations of the most significant porcine lipid QTL and
      those identified in humans. This finding might suggest that, in mammals, diverse
      polymorphisms located in a common set of genes are involved in the genetic
      variation of serum lipid levels.

PMID- 18812459
TI  - Central blockade of oxytocin receptors during mid-late gestation reduces
      amplitude of slow afterhyperpolarization in supraoptic oxytocin neurons.
AB  - The neurohypophysial hormone oxytocin (OT), synthesized in magnocellular
      paraventricular (PVN) and supraoptic (SON) nuclei, is well known for its effects
      in lactation. Our previous studies showed that central OT receptor (OTR) binding
      is increased during gestation and that blockade of central OTRs, specifically
      during mid-late gestation, causes a delay in OT release during suckling and
      reduces weight gain in pups, suggesting decreased milk delivery. In the present
      study, we tested whether central OTR blockade during late gestation disrupts the
      gestation-related plasticity in intrinsic membrane properties. Whole cell current
      clamp recordings were performed in OT neurons from pregnant rats (19-22 days in
      gestation) that were infused with an OTR antagonist (OTA) or artificial
      cerebrospinal fluid (aCSF) and from virgin rats infused with aCSF into the third
      ventricle via an osmotic minipump beginning on days 12-14 of gestation. The
      amplitudes of both Ca(2+)-dependent afterhyperpolarizations (AHPs), an apamin
      sensitive medium AHP (mAHP) and an apamin-insensitive slow AHP (sAHP), were
      significantly increased during late gestation in control pregnant animals.
      However, the amplitude of the sAHP from pregnant rats treated with the OTA was
      significantly smaller than that of pregnant control rats and similar to that of
      virgins. These results indicate that the diminished efficiency in lactation due
      to OTR blockade may be partly a result of an altered sAHP that would shape OT
      bursting. These findings suggest that central actions of OT during late gestation
      are necessary for programming the plasticity of at least some of the intrinsic
      membrane properties in OT neurons during lactation.

PMID- 18812460
TI  - The ubiquitin-proteasome and the mitochondria-associated apoptotic pathways are
      sequentially downregulated during recovery after immobilization-induced muscle
      atrophy.
AB  - Immobilization produces morphological, physiological, and biochemical alterations
      in skeletal muscle leading to muscle atrophy and long periods of recovery. Muscle
      atrophy during disuse results from an imbalance between protein synthesis and
      proteolysis but also between apoptosis and regeneration processes. This work
      aimed to characterize the mechanisms underlying muscle atrophy and recovery
      following immobilization by studying the regulation of the mitochondria
      associated apoptotic and the ubiquitin-proteasome-dependent proteolytic pathways.
      Animals were subjected to hindlimb immobilization for 4-8 days (I4 to I8) and
      allowed to recover after cast removal for 10-40 days (R10 to R40). Soleus and
      gastrocnemius muscles atrophied from I4 to I8 to a greater extent than extensor
      digitorum longus and tibialis anterior muscles. Gastrocnemius muscle atrophy was
      first stabilized at R10 before being progressively reduced until R40.
      Polyubiquitinated proteins accumulated from I4, whereas the increased
      ubiquitination rates and chymotrypsin-like activity of the proteasome were
      detectable from I6 to I8. Apoptosome and caspase-3 or -9 activities increased at
      I6 and I8, respectively. The ubiquitin-proteasome-dependent pathway was
      normalized early when muscle stops to atrophy (R10). By contrast, the
      mitochondria-associated apoptotic pathway was first downregulated below basal
      levels when muscle started to recover at R15 and completely normalized at R20.
      Myf 5 protein levels decreased from I4 to I8 and were normalized at R10.
      Altogether, our results suggest a two-stage process in which the ubiquitin
      proteasome pathway is rapidly up- and downregulated when muscle atrophies and
      recovers, respectively, whereas apoptotic processes may be involved in the late
      stages of atrophy and recovery.

PMID- 18812461
TI  - The alpha-subunit of AMPK is essential for submaximal contraction-mediated
      glucose transport in skeletal muscle in vitro.
AB  - AMP-activated protein kinase (AMPK) is a key signaling protein in the regulation
      of skeletal muscle glucose uptake, but its role in mediating contraction-induced
      glucose transport is still debated. The effect of contraction on glucose
      transport is impaired in EDL muscle of transgenic mice expressing a kinase-dead,
      dominant negative form of the AMPKalpha(2) subunit (KD-AMPKalpha(2) mice).
      However, maximal force production is reduced in this muscle, raising the
      possibility that the defect in glucose transport was due to a secondary decrease
      in force production and not impaired AMPKalpha(2) activity. Generation of force
      frequency curves revealed that muscle force production is matched between wild
      type (WT) and KD-AMPKalpha(2) mice at frequencies < or =50 Hz. Moreover, AMPK
      activation is already maximal at 50 Hz in muscles of WT mice. When EDL muscles
      from WT mice were stimulated at a frequency of 50 Hz for 2 min (200-ms train,
      1/s, 30 volts), contraction caused an approximately 3.5-fold activation of
      AMPKalpha(2) activity and an approximately 2-fold stimulation of glucose uptake.
      Conversely, whereas force production was similar in EDL of KD-AMPKalpha(2)
      animals, no effect of contraction was observed on AMPKalpha(2) activity, and
      glucose uptake stimulation was reduced by 50% (P < 0.01) As expected, 5
      aminoimidazole-4-carboxamide-1-beta-d-ribofuranosyl 5'-monophosphate (AICAR)
      caused a 2.3-fold stimulation of AMPKalpha(2) activity and a 1.7-fold increase in
      glucose uptake in EDL from WT mice, whereas no effect was detected in muscle from
      KD-AMPKalpha(2) mice. These data demonstrate that AMPK activation is essential
      for both AICAR and submaximal contraction-induced glucose transport in skeletal
      muscle but that AMPK-independent mechanisms are also involved.

PMID- 18812462
TI  - Evaluating the glucose tolerance test in mice.
AB  - The objective of this study was to determine the optimal conditions under which
      to assess glucose tolerance in chow- and high-fat-fed C57BL/6J mice. Mice were
      fed either chow or high-fat diet for 8 wk. Variables tested were fasting duration
      (0-, 3-, 6-, and 24-h and overnight fasting), route of administration
      (intraperitoneal vs. oral) load of glucose given (2, 1, or 0.5 g/kg and fixed 50
      mg dose), and state of consciousness. Basal glucose concentrations were increased
      in high-fat- compared with chow-fed mice following 6 h of fasting (9.1 +/- 0.3
      vs. 7.9 +/- 0.4 mmol/l P = 0.01). Glucose tolerance was most different and
      therefore significant (P = 0.001) in high-fat-fed mice after 6 h of fasting
      (1,973 +/- 96 vs. 1,248 +/- 83 mmol.l(-1).120 min(-1)). The difference in glucose
      tolerance was greater following an OGTT (142%), in contrast to an IPGTT, with a
      127% difference between high fat and chow. We also found that administering 2
      g/kg of glucose resulted in a greater level of significance (P = 0.0008) in
      glucose intolerance in high-fat- compared with chow-fed mice. A fixed dose of 50
      mg glucose regardless of body weight was enough to show glucose intolerance in
      high-fat- vs. chow-fed mice. Finally, high-fat-fed mice showed glucose
      intolerance compared with their chow-fed counterparts whether they were tested
      under conscious or anesthetized conditions. We conclude that 2 g/kg glucose
      administered orally following 6 h of fasting is best to assess glucose tolerance
      in mice under these conditions.

PMID- 18812463
TI  - Emerging roles for the ubiquitin-proteasome system and autophagy in pancreatic
      beta-cells.
AB  - Protein degradation in eukaryotic cells is mediated primarily by the ubiquitin
      proteasome system and autophagy. Turnover of protein aggregates and other
      cytoplasmic components, including organelles, is another function attributed to
      autophagy. The ubiquitin-proteasome system and autophagy are essential for normal
      cell function but under certain pathological conditions can be overwhelmed, which
      can lead to adverse effects in cells. In this review we will focus primarily on
      the insulin-producing pancreatic beta-cell. Pancreatic beta-cells respond to
      glucose levels by both producing and secreting insulin. The inability of beta
      cells to secrete sufficient insulin is a major contributory factor in the
      development of type 2 diabetes. The aim of this review is to examine some of the
      crucial roles of the ubiquitin-proteasome system and autophagy in normal
      pancreatic beta-cell function and how these pathways may become dysfunctional
      under pathological conditions associated with metabolic syndromes.

PMID- 18812464
TI  - Prepubertal OVX increases IGF-I expression and bone accretion in C57BL/6J mice.
AB  - It is generally well accepted that the pubertal surge in estrogen is responsible
      for the rapid bone accretion that occurs during puberty and that this effect is
      mediated by an estrogen-induced increase in growth hormone (GH)/insulin-like
      growth factor (IGF) action. To test the cause and effect relationship between
      estrogen and GH/IGF, we evaluated the consequence of ovariectomy (OVX) in
      prepubertal mice (C57BL/6J mice at 3 wk of age) on skeletal changes and the
      GH/IGF axis during puberty. Contrary to our expectations, OVX increased body
      weight (12-18%), bone mineral content (11%), bone length (4%), bone size (3%),
      and serum, liver, and bone IGF-I (30-50%) and decreased total body fat (18%) at 3
      wk postsurgery. To determine whether estrogen is the key ovarian factor
      responsible for these changes, we performed a second experiment in which OVX mice
      were treated with placebo or estrogen implants. In addition to observing similar
      results compared with our first experiment, estrogen treatment partially rescued
      the increased body weight and bone size and completely rescued body fat and IGF-I
      levels. The increased bone accretion in OVX mice was due to increased bone
      formation rate (as determined by bone histomorphometry) and increased serum
      procollagen peptide. In conclusion, contrary to the known estrogen effect as an
      initiator of GH/IGF surge and thereby pubertal growth spurt, our findings
      demonstrate that loss of estrogen and/or other hormones during the prepubertal
      growth period effect leads to an increase in IGF-I production and bone accretion
      in mice.

PMID- 18812465
TI  - Management of acute promyelocytic leukemia: recommendations from an expert panel
      on behalf of the European LeukemiaNet.
AB  - The introduction of all-trans retinoic acid (ATRA) and, more recently, arsenic
      trioxide (ATO) into the therapy of acute promyelocytic leukemia (APL) has
      revolutionized the management and outcome of this disease. Several treatment
      strategies using these agents, usually in combination with chemotherapy, but also
      without or with minimal use of cytotoxic agents, have provided excellent
      therapeutic results. Cure of APL patients, however, is also dependent on peculiar
      aspects related to the management and supportive measures that are crucial to
      counteract life-threatening complications associated with the disease biology and
      molecularly targeted treatment. The European LeukemiaNet recently appointed an
      international panel of experts to develop evidence- and expert opinion-based
      guidelines on the diagnosis and management of APL. Together with providing
      current indications on genetic diagnosis, modern risk-adapted front-line therapy
      and salvage treatment, the review contains specific recommendations for the
      identification and management of most important complications such as the
      bleeding disorder, APL differentiation syndrome, QT prolongation and other ATRA-
      and ATO-related toxicities, as well as for molecular assessment of response to
      treatment. Finally, the approach to special situations is also discussed,
      including management of APL in children, elderly patients, and pregnant women.

PMID- 18812466
TI  - Chronic lymphocytic leukemia antibodies with a common stereotypic rearrangement
      recognize nonmuscle myosin heavy chain IIA.
AB  - Leukemic B lymphocytes of a large group of unrelated chronic lymphocytic leukemia
      (CLL) patients express an unmutated heavy chain immunoglobulin variable (V)
      region encoded by IGHV1-69, IGHD3-16, and IGHJ3 with nearly identical heavy and
      light chain complementarity-determining region 3 sequences. The likelihood that
      these patients developed CLL clones with identical antibody V regions randomly is
      highly improbable and suggests selection by a common antigen. Monoclonal
      antibodies (mAbs) from this stereotypic subset strongly bind cytoplasmic
      structures in HEp-2 cells. Therefore, HEp-2 cell extracts were immunoprecipitated
      with recombinant stereotypic subset-specific CLL mAbs, revealing a major protein
      band at approximately 225 kDa that was identified by mass spectrometry as
      nonmuscle myosin heavy chain IIA (MYHIIA). Reactivity of the stereotypic mAbs
      with MYHIIA was confirmed by Western blot and immunofluorescence colocalization
      with anti-MYHIIA antibody. Treatments that alter MYHIIA amounts and cytoplasmic
      localization resulted in a corresponding change in binding to these mAbs. The
      appearance of MYHIIA on the surface of cells undergoing stress or apoptosis
      suggests that CLL mAb may generally bind molecules exposed as a consequence of
      these events. Binding of CLL mAb to MYHIIA could promote the development,
      survival, and expansion of these leukemic cells.

PMID- 18812467
TI  - Mesenchymal stromal cell-derived CCL2 suppresses plasma cell immunoglobulin
      production via STAT3 inactivation and PAX5 induction.
AB  - We demonstrate that the secretome of mesenchymal stromal cells (MSCs) suppresses
      plasma cell (PC) immunoglobulin (Ig) production, induces plasmablast
      proliferation, and leads to interleukin-10-mediated blockade in vitro. We found
      that these effects are the result of MSC-derived CC chemokine ligands CCL2 and
      CCL7. More specifically, MSCs further processed these CC chemokines by the
      activity of matrix metalloproteinases (MMPs), leading to the generation of
      proteolytically processed antagonistic CCL2 variant. Neutralizing CCL2 or
      inhibiting MMP enzymatic activity abolished the PC-suppressive effect of MSCs. We
      also observed that MMP-processed CCL2 suppresses signal transducer and activator
      of transcription 3 (STAT3) activation in PC. As a result, the transcription
      factor PAX5 is induced, thus explaining the inhibition of Ig synthesis. The
      absence of inhibitory effects by MSC on the humoral response of CCR2(-/-) mice to
      xenoantigen suggests that MMP-cleaved CCL2/CCR2 interaction as well as downstream
      phosphatase activity is necessary for antagonistic effect. We tested syngeneic
      MSCs in hemophilic B6 mice with predeveloped antihuman factor VIII (hFVIII)
      antibodies and demonstrated a robust decrease in hFVIII-specific IgG levels.
      Thus, MSCs may play a role in modulating Ig production by PCs via MMP processing
      of CCL2 and may represent an appealing cell therapy approach for pathologic
      humoral responses.

PMID- 18812468
TI  - Central role of Sp1-regulated CD39 in hypoxia/ischemia protection.
AB  - Hypoxia is common to several inflammatory diseases, where multiple cell types
      release adenine-nucleotides (particularly adenosine triphosphate/adenosine
      diphosphate). Adenosine triphosphate/adenosine diphosphate is metabolized to
      adenosine through a 2-step enzymatic reaction initiated by CD39 (ectonucleoside
      triphosphate-diphosphohydrolase-1). Thus, extracellular adenosine becomes
      available to regulate multiple inflammatory endpoints. Here, we hypothesized that
      hypoxia transcriptionally up-regulates CD39 expression. Initial studies revealed
      hypoxia-dependent increases in CD39 mRNA and immunoreactivity on endothelia.
      Examination of the human CD39 gene promoter identified a region important in
      hypoxia inducibility. Multiple levels of analysis, including site-directed
      mutagenesis, chromatin immunoprecipitation, and inhibition by antisense, revealed
      a critical role for transcription-factor Sp1 in hypoxia-induction of CD39. Using
      a combination of cd39(-/-) mice and Sp1 small interfering RNA in in vivo cardiac
      ischemia models revealed Sp1-mediated induction of cardiac CD39 during myocardial
      ischemia. In summary, these results identify a novel Sp1-dependent regulatory
      pathway for CD39 and indicate the likelihood that CD39 is central to protective
      responses to hypoxia/ischemia.

PMID- 18812469
TI  - Dendritic cells drive memory CD8 T-cell homeostasis via IL-15 transpresentation.
AB  - Interleukin-15 (IL-15) is crucial for the development of naive and memory CD8 T
      cells and is delivered through a mechanism called transpresentation. Previous
      studies showed that memory CD8 T cells require IL-15 transpresentation by an as
      yet unknown cell of hematopoietic origin. We hypothesized that dendritic cells
      (DCs) transpresent IL-15 to CD8 T cells, and we examined this by developing a
      transgenic model that limits IL-15 transpresentation to DCs. In this study, IL-15
      transpresentation by DCs had little effect on restoring naive CD8 T cells but
      contributed to the development of memory-phenotype CD8 T cells. The generation of
      virus-specific, memory CD8 T cells was partially supported by IL-15Ralpha(+) DCs
      through the preferential enhancement of a subset of KLRG-1(+)CD27(-) CD8 T cells.
      In contrast, these DCs were largely sufficient in driving normal homeostatic
      proliferation of established memory CD8 T cells, suggesting that memory CD8 T
      cells grow more dependent on IL-15 transpresentation by DCs. Overall, our study
      clearly supports a role for DCs in memory CD8 T-cell homeostasis but also
      provides evidence that other hematopoietic cells are involved in this function.
      The identification of DCs fulfilling this role will enable future studies to
      better focus on mechanisms regulating T-cell homeostasis.

PMID- 18812470
TI  - Cyclic AMP plays a critical role in C3a-receptor-mediated regulation of dendritic
      cells in antigen uptake and T-cell stimulation.
AB  - The biochemical basis for complement acting directly on antigen-presenting cells
      to enhance their function in T-cell stimulation has been unclear. Here we present
      evidence that engagement of C3a receptor (C3aR) on the surface of dendritic cells
      (DCs) leads to alterations in the level of intracellular cyclic adenosine
      monophosphate (cAMP), a potent negative regulator of inflammatory cytokines. C3aR
      activation-induced depression of cAMP was associated with enhanced capacity of
      DCs for antigen uptake and T-cell stimulation. Conversely, C3aR-deficient DCs
      showed elevation of cAMP and impaired properties for antigen uptake and immune
      stimulation. Similarities in the phenotype of C3-deficient and C3aR-deficient DCs
      suggest that local production of C3 with extracellular metabolism to C3a is an
      important driver of DC alterations in cAMP. The finding of a link between
      complement and adaptive immune stimulation through cAMP offers new insight into
      how innate and adaptive immunity combine to generate efficient effector and
      memory responses.

PMID- 18812471
TI  - Stable transduction of quiescent T cells without induction of cycle progression
      by a novel lentiviral vector pseudotyped with measles virus glycoproteins.
AB  - A major limitation of current lentiviral vectors (LVs) is their inability to
      govern efficient gene transfer into quiescent cells such as primary T cells,
      which hampers their application for gene therapy. Here we generated high-titer
      LVs incorporating Edmonston measles virus (MV) glycoproteins H and F on their
      surface. They allowed efficient transduction through the MV receptors, SLAM and
      CD46, both present on blood T cells. Indeed, these H/F-displaying vectors
      outperformed by far VSV-G-LVs for the transduction of IL-7-prestimulated T cells.
      More importantly, a single exposure to these H/F-LVs allowed efficient gene
      transfer in quiescent T cells, which are not permissive for VSV-G-LVs that need
      cell-cycle entry into the G1b phase for efficient transduction. High-level
      transduction of resting memory (50%) and naive (11%) T cells with H/F-LVs, which
      seemed to occur mainly through SLAM, was not at cost of cell-cycle entry or of
      target T-cell activation. Finally, the naive or memory phenotypes of transduced
      resting T cells were maintained and no changes in cytokine profiles were
      detected, suggesting that T-cell populations were not skewed. Thus, H/F-LV
      transduction of resting T cells overcomes the limitation of current lentiviral
      vectors and may improve the efficacy of T cell-based gene therapy.

PMID- 18812472
TI  - Immunotransplantation preferentially expands T-effector cells over T-regulatory
      cells and cures large lymphoma tumors.
AB  - Ex vivo-expanded tumor-infiltrating lymphocytes infused into lymphodepleted
      recipients has clear antitumor efficacy. More practical sources of such antitumor
      lymphocytes would broaden the application of this approach. Previously, we
      described an in situ vaccination combining chemotherapy with intratumoral
      injection of CpG-enriched oligonucleotides, which induced T-cell immunity against
      established lymphoma. An ongoing clinical trial of this maneuver has demonstrated
      clinical responses in lymphoma patients. Here, we use this vaccine maneuver to
      generate immune cells for transfer into irradiated, syngeneic recipients.
      Transferred tumor-specific T-effector (T(eff)) cells preferentially expanded,
      increasing the T(eff)/T-regulatory (T(reg)) ratio in these
      "immunotransplantation" recipients and curing large and metastatic tumors. Donor
      T cells were necessary for tumor protection, and CD8 T-cell immune responses were
      enhanced by posttransplantation booster vaccination. Hematopoietic stem cell
      transplantation is a standard therapy for lymphoma. Therefore, in situ tumor
      vaccination followed by immunotransplantation of harvested tumor-specific T cells
      could be directly tested in clinical trials to treat otherwise resistant
      malignancies.

PMID- 18812473
TI  - Trisomy 21 enhances human fetal erythro-megakaryocytic development.
AB  - Children with Down syndrome exhibit 2 related hematopoietic diseases: transient
      myeloproliferative disorder (TMD) and acute megakaryoblastic leukemia (AMKL).
      Both exhibit clonal expansion of blasts with biphenotypic erythroid and
      megakaryocytic features and contain somatic GATA1 mutations. While altered GATA1
      inhibits erythro-megakaryocytic development, less is known about how trisomy 21
      impacts blood formation, particularly in the human fetus where TMD and AMKL
      originate. We used in vitro and mouse transplantation assays to study
      hematopoiesis in trisomy 21 fetal livers with normal GATA1 alleles. Remarkably,
      trisomy 21 progenitors exhibited enhanced production of erythroid and
      megakaryocytic cells that proliferated excessively. Our findings indicate that
      trisomy 21 itself is associated with cell-autonomous expansion of erythro
      megakaryocytic progenitors. This may predispose to TMD and AMKL by increasing the
      pool of cells susceptible to malignant transformation through acquired mutations
      in GATA1 and other cooperating genes.

PMID- 18812474
TI  - In vivo proliferation advantage of genetically corrected hematopoietic stem cells
      in a mouse model of Fanconi anemia FA-D1.
AB  - Fanconi anemia (FA) is an inherited recessive DNA repair disorder mainly
      characterized by bone marrow failure and cancer predisposition. Studies in mosaic
      FA patients have shown that reversion of one inherited germ-line mutation
      resulting in a functional allele in one or a few hematopoietic stem cells (HSCs)
      can lead to the proliferation advantage of corrected cells, thus over time
      normalizing the hematologic status of the patient. In contrast to these
      observations, it is still unclear whether ex vivo genetic correction of FA HSCs
      also provides a similar proliferation advantage to FA HSCs. Using an FA mouse
      model with a marked hematopoietic phenotype, the FA-D1 (Brca2(Delta27/Delta27))
      mice, we demonstrate that the lentivirus-mediated gene therapy of FA HSCs results
      in the progressive expansion of genetically corrected clones in mild-conditioned
      FA-D1 recipients. Consistent with these data, hematopoietic progenitors from FA
      recipients progressively became mitomycin C resistant and their chromosomal
      instability was reverted. No evidence of myelodysplasia, leukemias, or abnormal
      clonal repopulation was observed at multiple time points in primary or secondary
      recipients. Our results demonstrate that ectopic expression of BRCA2 confers a
      beneficial in vivo proliferation advantage to FA-D1 HSCs that enables the full
      hematopoietic repopulation of FA recipients with genetically corrected cells.

PMID- 18812475
TI  - A newly identified isoform of Slp2a associates with Rab27a in cytotoxic T cells
      and participates to cytotoxic granule secretion.
AB  - Cytotoxic T lymphocytes (CTLs) and natural killer cells help control infections
      and tumors via a killing activity that is mediated by the release of cytotoxic
      granules. Granule secretion at the synapse formed between the CTL and the target
      cell leads to apoptosis of the latter. This process involves polarization of the
      CTL's secretory machinery and cytotoxic granules. The small GTPase Rab27a and the
      hMunc13-4 protein have been shown to be required for both granule maturation and
      granule docking and priming at the immunologic synapse. Using a tandem affinity
      purification technique, we identified a previously unknown hematopoietic form of
      Slp2a (Slp2a-hem) and determined that it is a specific effector of the active
      form of Rab27a. This interaction occurs in vivo in primary CTLs. We have shown
      that (1) Rab27a recruits Slp2a-hem on vesicular structures in peripheral CTLs and
      (2) following CTL-target cell conjugate formation, the Slp2a-hem/Rab27a complex
      colocalizes with perforin-containing granules at the immunologic synapse, where
      it binds to the plasma membrane through its C2 domains. The overexpression of a
      dominant-negative form of Slp2a-hem markedly impaired exocytosis of cytotoxic
      granules-indicating that Slp2a is required for cytotoxic granule docking at the
      immunologic synapse.

PMID- 18812476
TI  - Pharmacodynamics, pharmacokinetics, safety, and tolerability of albiglutide, a
      long-acting glucagon-like peptide-1 mimetic, in patients with type 2 diabetes.
AB  - CONTEXT: Native glucagon-like peptide-1 increases insulin secretion, decreases
      glucagon secretion, and reduces appetite but is rapidly inactivated by dipeptidyl
      peptidase-4. Albiglutide is a novel dipeptidyl peptidase-4-resistant glucagon
      like peptide-1 dimer fused to human albumin designed to have sustained efficacy
      in vivo. OBJECTIVES: The objectives were to investigate pharmacodynamics,
      pharmacokinetics, safety, and tolerability of albiglutide in type 2 diabetes
      subjects. METHODS: In a single-blind dose-escalation study, 54 subjects were
      randomized to receive placebo or 9-, 16-, or 32-mg albiglutide on d 1 and 8. In a
      complementary study, 46 subjects were randomized to a single dose (16 or 64 mg)
      of albiglutide to the arm, leg, or abdomen. RESULTS: Significant dose-dependent
      reductions in 24-h mean weighted glucose [area under the curve((0-24 h))] were
      observed, with placebo-adjusted least squares means difference values in the 32
      mg cohort of -34.8 and -56.4 mg/dl [95% confidence interval (-54.1, -15.5) and (
      82.2, -30.5)] for d 2 and 9, respectively. Placebo-adjusted fasting plasma
      glucose decreased by -26.7 and -50.7 mg/dl [95% confidence interval (-46.3, 
      7.06) and (-75.4, -26.0)] on d 2 and 9, respectively. Postprandial glucose was
      also reduced. No hypoglycemic episodes were detected in the albiglutide cohorts.
      The frequency and severity of the most common adverse events, headache and
      nausea, were comparable with placebo controls. Albiglutide half-life ranged
      between 6 and 7 d. The pharmacokinetics or pharmacodynamic of albiglutide was
      unaffected by injection site. CONCLUSIONS: Albiglutide improved fasting plasma
      glucose and postprandial glucose with a favorable safety profile in subjects with
      type 2 diabetes. Albiglutide's long half-life may allow for once-weekly or less
      frequent dosing.

PMID- 18812477
TI  - Mortality in women with turner syndrome in Great Britain: a national cohort
      study.
AB  - CONTEXT: Turner syndrome is characterized by complete or partial X chromosome
      monosomy. It is associated with substantial morbidity, but mortality risks and
      causes of death are not well described. OBJECTIVES: Our objective was to
      investigate mortality and causes of death in women with Turner syndrome. DESIGN
      AND SETTING: We constructed a cohort of women diagnosed with Turner syndrome at
      almost all cytogenetic centers in Great Britain and followed them for mortality.
      PATIENTS: A total of 3,439 women diagnosed between 1959-2002 were followed to the
      end of 2006. OUTCOME MEASURES: Standardized mortality ratios (SMRs) and absolute
      excess risks were evaluated. RESULTS: In total, 296 deaths occurred. Mortality
      was significantly raised overall [SMR = 3.0; 95% confidence interval (CI) = 2.7
      3.4] and was raised for nearly all major causes of death. Circulatory disease
      accounted for 41% of excess mortality, with greatest SMRs for aortic aneurysm
      (SMR = 23.6; 95% CI = 13.8-37.8) and aortic valve disease (SMR = 17.9; 95% CI =
      4.9-46.0), but SMRs were also raised for other circulatory conditions. Other
      major contributors to raised mortality included congenital cardiac anomalies,
      diabetes, epilepsy, liver disease, noninfectious enteritis and colitis, renal and
      ureteric disease, and pneumonia. Absolute excess risks of death were considerably
      greater at older than younger ages. CONCLUSIONS: Mortality in women with Turner
      syndrome is 3-fold higher than in the general population, is raised for almost
      all major causes of death, and is raised at all ages, with the greatest excess
      mortality in older adulthood. These risks need consideration in follow-up and
      counseling of patients and add to reasons for continued follow-up and preventive
      measures in adult, not just pediatric, care.

PMID- 18812478
TI  - Change of serum antithyroglobulin antibody levels is useful for prediction of
      clinical recurrence in thyroglobulin-negative patients with differentiated
      thyroid carcinoma.
AB  - OBJECTIVES: The aim of the study was to evaluate the usefulness of the
      antithyroglobulin autoantibody (TgAb) value at 6-12 months after remnant ablation
      in predicting recurrence in differentiated thyroid carcinoma patients who had
      undetectable thyroglobulin (Tg) values. The change in TgAb concentration measured
      between the time of remnant ablation (TgAb1) and 6-12 months thereafter (TgAb2)
      was also evaluated as a possible prognostic indicator. PATIENTS AND METHODS:
      Patients with differentiated thyroid carcinoma who underwent total thyroidectomy
      followed by (131)I remnant ablation between 1995 and 2003 at the Asan Medical
      Center (Seoul, Korea) were enrolled. Of these, 824 patients with undetectable Tg
      at 6-12 months after remnant ablation during thyroid hormone withdrawal were the
      subjects of this study. RESULTS: TgAb2 was positive in 56 patients. Ten of 56
      patients (18%) with positive TgAb2 had recurrence, whereas only 10 of 768
      patients (1%) with negative TgAb2 had recurrence during 73.6 months of follow-up
      (P < 0.001). The change between TgAb1 and TgAb2 levels was evaluated in patients
      with positive TgAb2. TgAb concentration decreased by more than 50% in 21 patients
      (group 1) and by less than 50% in 16 patients (group 2), and it increased in 19
      patients (group 3). The recurrence rates in groups 1, 2, and 3 were 0, 19, and
      37%, respectively (P = 0.016). CONCLUSIONS: Serum TgAb levels measured at 6-12
      months after remnant ablation could predict recurrence in patients with
      undetectable Tg values. In patients with undetectable Tg and positive TgAb
      values, a change in TgAb concentration during the early postoperative period may
      be a prognostic indicator of recurrence.

PMID- 18812479
TI  - GNAS defects identified by stimulatory G protein alpha-subunit signalling studies
      in platelets.
AB  - CONTEXT: GNAS is an imprinted region that gives rise to several transcripts,
      antisense transcripts, and noncoding RNAs, including transcription of RNA
      encoding the alpha-subunit of the stimulatory G protein (Gsalpha). The complexity
      of the GNAS cluster results in ubiquitous genomic imprints, tissue-specific
      Gsalpha expression, and multiple genotype-phenotype relationships. Phenotypes
      resulting from genetic and epigenetic abnormalities of the GNAS region include
      Albright's hereditary osteodystrophy, pseudohypoparathyroidism types Ia (PHPIa)
      and Ib (PHPIb), and pseudopseudohypoparathyroidism (PPHP). OBJECTIVE: The aim was
      to study the complex GNAS pathology by a functional test as an alternative to the
      generally used but labor-intensive erythrocyte complementation assay. DESIGN AND
      PATIENTS: We report the first platelet-based diagnostic test for Gsalpha
      hypofunction, supported by clinical, biochemical, and molecular data for six
      patients with PHPIa or PPHP and nine patients with PHPIb. The platelet test is
      based on the inhibition of platelet aggregation by cAMP, produced after Gsalpha
      stimulation. RESULTS: Platelets are easily accessible, and platelet aggregation
      responses were found to reflect Gsalpha signaling defects in patients, in
      concordance with the patient's phenotype and genotype. Gsalpha hypofunction in
      PHPIa and PPHP patients with GNAS mutations was clearly detected by this method.
      Mildly decreased or normal Gsalpha function was detected in patients with PHPIb
      with either an overall or exon 1A-only epigenetic defect, respectively. Platelet
      Gsalpha expression was reduced in both PHPIb patient groups, whereas XLalphas was
      up-regulated only in PHPIb patients with the broad epigenetic defect. CONCLUSION:
      The platelet-based test is a novel tool for establishing the diagnosis of Gsalpha
      defects, which may otherwise be quite challenging.

PMID- 18812480
TI  - Association of the timing of puberty with a chromosome 2 locus.
AB  - CONTEXT: Twin studies indicate that the timing of pubertal onset is under strong
      genetic control. However, genes controlling pubertal timing in the general
      population have not yet been identified. OBJECTIVE: To facilitate the
      identification of genes influencing the timing of pubertal growth and maturation,
      we conducted linkage mapping of constitutional delay of growth and puberty
      (CDGP), an extreme variant of normal pubertal timing, in extended families.
      PARTICIPANTS AND METHODS: Fifty-two families multiply affected with CDGP were
      genotyped with 383 multiallelic markers. CDGP was defined based on growth charts
      (the age at onset of growth spurt, peak height velocity, or attaining adult
      height taking place at least 1.5 sd later than average). Chromosomal regions
      cosegregating with CDGP were identified with parametric affected-only linkage
      analysis using CDGP as a dichotomized trait. RESULTS: The genome-wide scan
      detected linkage of CDGP to a region on chromosome 2p13-2q13. The two-point
      heterogeneity LOD (HLOD) score was 1.62 (alpha = 0.27), and the corresponding
      multipoint HLOD was 2.54 (alpha = 0.31). Fine-mapping the region at 1 cM
      resolution increased the multipoint HLOD score to 4.44 (alpha = 0.41). The
      linkage became weaker if family members diagnosed with CDGP without growth data
      were also included in the analyses. CONCLUSIONS: The pericentromeric region of
      chromosome 2 harbors a gene predisposing to pubertal delay in multiply affected
      pedigrees. Our data suggest that this locus may be a component of the internal
      clock controlling the timing of the onset of puberty.

PMID- 18812481
TI  - Ultrasound screening for thyroid carcinoma in childhood cancer survivors: a case
      series.
AB  - CONTEXT: Childhood cancer survivors need regular monitoring into young adulthood
      and beyond, because they are at risk for developing late-onset complications of
      cancer therapy, including second malignancies. OBJECTIVE: This study focuses on
      the use of thyroid ultrasound to screen for thyroid carcinoma in a population of
      childhood cancer survivors. PATIENTS: A total of 129 subjects who had received
      radiotherapy to the head, neck, or upper thorax for a pediatric cancer were
      studied in the setting of a long-term follow-up unit. DESIGN: Thyroid ultrasound
      usually began 5 yr after radiotherapy and was repeated every third year, if
      negative. Median follow-up time since childhood cancer diagnosis was 15.8 yr
      (range 6.1-34.8 yr). Solid thyroid nodules were found in 35 patients. Fine-needle
      aspiration was performed in 19 patients, of which 14 had nodules above 1 cm. MAIN
      OUTCOME MEASURE: The main outcome measure was the finding of not palpable thyroid
      cancers. RESULTS: Cytological examination of specimens diagnosed papillary
      carcinoma in five patients who underwent surgery. The cytological diagnosis of
      papillary thyroid carcinoma was confirmed in all cases by histological
      examination. Notably, only two of these patients had palpable nodules; the other
      three were smaller than 1 cm and were detected only by ultrasound. However,
      histological examination showed nodal metastases in two of these. CONCLUSIONS:
      Although ultrasound screening for thyroid cancer in the general population is not
      cost effective and could lead to unnecessary surgery, due to false positives, we
      believe that in childhood cancer survivors who received radiotherapy involving
      the head, neck, or upper thorax, it would be worthwhile.

PMID- 18812482
TI  - Prevalence of metabolic syndrome and related characteristics in obese adolescents
      with and without polycystic ovary syndrome.
AB  - CONTEXT: Adults with polycystic ovary syndrome (PCOS) may be at increased risk
      for metabolic syndrome (MBS) and related cardiovascular disease. It is not clear
      whether PCOS diagnosed in adolescence increases the risk of MBS in this age
      group. OBJECTIVE: The aim was to compare the prevalence and related
      characteristics of MBS in obese adolescents with and without PCOS. DESIGN: We
      conducted a cross-sectional study of overweight and obese PCOS adolescents and
      BMI matched controls. PATIENTS AND PARTICIPANTS: A total of 74 subjects, 43 with
      PCOS and 31 controls, participated in the study. INTERVENTIONS: Each subject
      underwent a physical examination and laboratory evaluation for a diagnosis of
      MBS. Regional fat distribution was determined by computerized tomography scan in
      the PCOS adolescents. MAIN OUTCOME MEASURES: We measured the prevalence of MBS
      and its components in adolescent subjects and controls. RESULTS: The PCOS group
      had larger ovarian volume and higher measures of total testosterone and free
      androgen index than controls, but there were no differences in waist
      circumference, fasting glucose, blood pressure, or lipids. PCOS adolescents
      demonstrated more glucose abnormalities and higher plasminogen activator
      inhibitor-1. By pediatric criteria, 53% of the PCOS and 55% of the control
      adolescents had MBS. By adult criteria, 26% of PCOS and 29% of controls met
      diagnostic criteria for MBS. CONCLUSIONS: Obese adolescent women have a high
      prevalence of MBS, and PCOS does not add additional risk for MBS. There appears
      to be an association between MBS and visceral adiposity. PCOS is associated with
      increased incidence of glucose intolerance and increased plasminogen activator
      inhibitor-1. Our results reinforce the importance of obesity counseling in
      adolescents to recognize the possible risk of future cardiovascular disease in
      these young women.

PMID- 18812483
TI  - Effects of perilipin (PLIN) gene variation on metabolic syndrome risk and weight
      loss in obese children and adolescents.
AB  - CONTEXT: Genetic polymorphisms at the perilipin (PLIN) locus have been
      investigated for their potential utility as markers for obesity and metabolic
      syndrome (MS). We examined in obese children and adolescents (OCA) aged 7-14 yr
      the association of single-nucleotide polymorphisms (SNP) at the PLIN locus with
      anthropometric, metabolic traits, and weight loss after 20-wk multidisciplinary
      behavioral and nutritional treatment without medication. DESIGN: A total of 234
      OCA [body mass index (BMI = 30.4 +/- 4.4 kg/m(2); BMI Z-score = 2.31 +/- 0.4)
      were evaluated at baseline and after intervention. We genotyped four SNPs (PLIN1
      6209T-->C, PLIN4 11482G-->A, PLIN5 13041A-->G, and PLIN6 14995A-->T). RESULTS:
      Allele frequencies were similar to other populations, PLIN1 and PLIN4 were in
      linkage disequilibrium (D' = 0.999; P < 0.001). At baseline, no anthropometric
      differences were observed, but minor allele A at PLIN4 was associated with higher
      triglycerides (111 +/- 49 vs. 94 +/- 42 mg/dl; P = 0.003), lower high-density
      lipoprotein cholesterol (40 +/- 9 vs. 44 +/- 10 mg/dl; P = 0.003) and higher
      homeostasis model assessment for insulin resistance (4.0 +/- 2.3 vs. 3.5 +/- 2.1;
      P = 0.015). Minor allele A at PLIN4 was associated with MS risk (age and sex
      adjusted) hazard ratio 2.4 (95% confidence interval = 1.1-4.9) for genotype GA
      and 3.5 (95% confidence interval = 1.2-9.9) for AA. After intervention, subjects
      carrying minor allele T at PLIN6 had increased weight loss (3.3 +/- 3.7 vs. 1.9
      +/- 3.4 kg; P = 0.002) and increased loss of the BMI Z-score (0.23 +/- 0.18 vs.
      0.18 +/- 0.15; P = 0.003). Due to group size, risk of by-chance findings cannot
      be excluded. CONCLUSION: The minor A allele at PLIN4 was associated with higher
      risk of MS at baseline, whereas the PLIN6 SNP was associated with better weight
      loss, suggesting that these polymorphisms may predict outcome strategies based on
      multidisciplinary treatment for OCA.

PMID- 18812484
TI  - Two common haplotypes of the glucocorticoid receptor gene are associated with
      increased susceptibility to cardiovascular disease in men with familial
      hypercholesterolemia.
AB  - CONTEXT: Glucocorticoids contribute to the development of atherosclerosis. Four
      polymorphisms in the glucocorticoid receptor (GR) gene have been reported to
      alter glucocorticoid sensitivity and have been associated with cardiovascular
      risk factors. Studies on the relationship between these GR variants and
      cardiovascular disease (CVD) risk, however, have yielded conflicting results.
      OBJECTIVE: We sought to determine whether haplotypes based on functional
      polymorphisms in the GR gene influenced susceptibility to CVD in a high-risk
      population. DESIGN, SETTING, AND PARTICIPANTS: In a multicenter cohort study,
      1830 patients with heterozygous familial hypercholesterolemia were genotyped for
      the functional ER22/23EK, N363S, BclI, and 9beta variants. We analyzed the
      combined effect of all GR variants by constructing haplotypes and using a Cox
      proportional hazards regression model with adjustment for year of birth and
      smoking. The analyses were stratified for sex. MAIN OUTCOME MEASURES: The primary
      outcome measure was CVD defined as coronary, cerebral, and peripheral artery
      disease. RESULTS: A total of 359 men (40.8%) and 224 women (23.6%) had a
      cardiovascular event. In men, the BclI haplotype was associated with a 34% higher
      CVD risk (confidence interval 1.02-1.76; P = 0.03) and the 9beta haplotype with a
      41% higher CVD risk (confidence interval 1.02-1.94; P = 0.04). In women, none of
      the GR haplotypes was significantly related with CVD. We did not find differences
      in cardiovascular risk factors between GR haplotypes. CONCLUSIONS: In this large
      cohort of high-risk individuals, two common haplotypes in the GR gene modified
      CVD susceptibility among men.

PMID- 18812485
TI  - Prospective study of high-dose cabergoline treatment of prolactinomas in 150
      patients.
AB  - CONTEXT: Cabergoline fails to normalize hyperprolactinemia in a considerable
      proportion of prolactinomas, especially macroadenomas. OBJECTIVE: We examined the
      effect of individualized high-dose cabergoline treatment on hyperprolactinemia in
      prolactinomas. PATIENTS: The study included 122 women and 28 men (93
      microadenomas and 57 macroadenomas). Forty-seven had undergone transsphenoidal
      surgery. According to the preceding medical treatment, the participants were
      separated into untreated (group U; n = 60), intolerant (group I; n = 64), and
      resistant (group R; n = 26) groups. INTERVENTIONS: We promptly increased
      cabergoline dose on the basis of individual prolactin levels. Length of treatment
      was 1 yr. RESULTS: Cabergoline normalized hyperprolactinemia in all patients
      except one. The proportion of prolactin normalization in both groups U and I was
      83% at 3 months and 95% at 6 months. By contrast, that in group R was 35% at 3
      months and 58% at 6 months. Mean cabergoline dose in milligrams per week at the
      time of prolactin normalization was 2.0 +/- 0.3 in group U, 0.9 +/- 0.1 in group
      I, and 5.2 +/- 0.6 in group R. Prolactin normalization rate at the 3 mg/wk dose
      was 84% overall but only 35% in group R. Serum progesterone or testosterone
      levels, diminished in 122 women or 16 men, respectively, were recovered in all
      except one resistant and four postmenopausal or panhypopituitary patients.
      CONCLUSION: Individualized high-dose cabergoline treatment can normalize
      hyperprolactinemia and hypogonadism in nearly all prolactinomas irrespective of
      tumor size or preceding treatments. Hyperprolactinemia could be controlled in
      poor responders within 1 yr with doses higher than 3 mg/wk.

PMID- 18812487
TI  - Phonological awareness in preschoolers with spoken language impairment: toward a
      better understanding of causal relationships and effective intervention. a
      constructive comment on Rvachew and Grawburg's (2006) study.
AB  - PURPOSE: This comment refers to a recent study of S. Rvachew and M. Grawburg
      (2006) that compared the fit of 2 models of the relationships among speech
      perception, receptive vocabulary, articulation, phonological awareness, and
      emergent literacy knowledge in preschoolers with speech sound disorders.
      CONCLUSION: It is argued that phonological working memory is an important
      additional variable to be included in the model preferred by Rvachew and Grawburg
      (2006). Furthermore, the model should take into account the reciprocal
      relationship between phonological awareness and emergent literacy skills that is
      already evident at the preschool level. This could lead to a more precise
      assessment of preschoolers with speech impairment and, above all, to more
      efficient preventive intervention.

PMID- 18812486
TI  - Increases in bone mineral density in response to oral dehydroepiandrosterone
      replacement in older adults appear to be mediated by serum estrogens.
AB  - CONTEXT: The mechanisms by which dehydroepiandrosterone (DHEA) replacement
      increases bone mineral density (BMD) in older adults are not known. OBJECTIVE:
      The aims were to determine the effects of DHEA therapy on changes in sex hormones
      and IGF-I and their associations with changes in BMD. DESIGN, SETTING, AND
      PARTICIPANTS: A randomized, double-blinded, placebo-controlled trial was
      conducted at an academic research institution. Participants were 58 women and 61
      men, aged 60-88 yr, with low serum DHEA sulfate (DHEAS) levels. INTERVENTION: The
      intervention was oral DHEA 50 mg/d or placebo for 12 months. MAIN OUTCOME
      MEASURES: BMD and serum DHEAS, testosterone, estradiol (E(2)), estrone (E(1)),
      SHBG, IGF-I, and IGF binding protein 3 were measured before and after
      intervention. Free testosterone and estrogen (FEI) indices were calculated.
      RESULTS: The average changes in hip and spine BMD (DHEA vs. placebo) ranged from
      1.1 to 1.6%. Compared with placebo, DHEA replacement increased serum DHEAS,
      testosterone, free testosterone index, E(1), E(2), FEI, and IGF-I (all P < 0.001)
      and decreased SHBG (P = 0.02) in women and, in men, increased DHEAS, E(1), FEI
      (all P < 0.001), and E(2) (P = 0.02) and decreased SHBG (P = 0.037). The changes
      in total and regional hip BMD were associated with 12-month E(2) (all P <or=
      0.001) and FEI (all P <or= 0.013). The effects of DHEA treatment were eliminated
      by adjustment for 12-month E(2). CONCLUSIONS: The significant increases in hip
      BMD in older adults undergoing DHEA replacement were mediated primarily by
      increases in serum E(2) rather than direct effects of DHEAS.

PMID- 18812489
TI  - Evidence-based systematic review: effects of intensity of treatment and
      constraint-induced language therapy for individuals with stroke-induced aphasia.
AB  - PURPOSE: This systematic review summarizes evidence for intensity of treatment
      and constraint-induced language therapy (CILT) on measures of language impairment
      and communication activity/participation in individuals with stroke-induced
      aphasia. METHOD: A systematic search of the aphasia literature using 15
      electronic databases (e.g., PubMed, CINAHL) identified 10 studies meeting
      inclusion/exclusion criteria. A review panel evaluated studies for methodological
      quality. Studies were characterized by research stage (i.e., discovery, efficacy,
      effectiveness, cost-benefit/public policy research), and effect sizes (ESs) were
      calculated wherever possible. RESULTS: In chronic aphasia, studies provided
      modest evidence for more intensive treatment and the positive effects of CILT. In
      acute aphasia, 1 study evaluated high-intensity treatment positively; no studies
      examined CILT. Four studies reported discovery research, with quality scores
      ranging from 3 to 6 of 8 possible markers. Five treatment efficacy studies had
      quality scores ranging from 5 to 7 of 9 possible markers. One study of treatment
      effectiveness received a score of 4 of 8 possible markers. CONCLUSION: Although
      modest evidence exists for more intensive treatment and CILT for individuals with
      stroke-induced aphasia, the results of this review should be considered
      preliminary and, when making treatment decisions, should be used in conjunction
      with clinical expertise and the client's individual values.

PMID- 18812490
TI  - A longitudinal study of speech timing in young children later found to have
      reading disability.
AB  - PURPOSE: This study examined the development of timing characteristics in early
      spontaneous speech of children who were later identified as having reading
      disability (RD). METHOD: Child-adult play sessions were recorded longitudinally
      at 2 and 3 years of age in 27 children, most of whom were at high familial risk
      for RD. For each speaking turn, the number of syllables was determined and an
      acoustic analysis measured the time allocated to articulation, pausing before
      speaking, and pausing during speaking. RESULTS: In grade school, a reading
      battery identified 9 children with RD and 18 children without RD (9 at high risk,
      9 at low risk). Early speaking rate was significantly slower in the group with
      RD, with significantly different patterns of pausing compared with children
      without RD. Group differences became more distinct by age 3, as longer speaking
      turns were attempted. CONCLUSIONS: The results are discussed in terms of speech
      and language formulation. Phonetic plans may be shorter and/or less specified in
      children with RD, surfacing as slow, short speaking turns with increased pausing
      relative to articulation. This explanation is consistent with several accounts of
      RD and provides a perspective on how speech and language deficits may manifest
      during spontaneous verbal interactions between young children and adults.

PMID- 18812491
TI  - Inhibition of native and recombinant nicotinic acetylcholine receptors by the
      myristoylated alanine-rich C kinase substrate peptide.
AB  - A variety of peptide ligands are known to inhibit the function of neuronal
      nicotinic acetylcholine receptors (nAChRs), including small toxins and brain
      derived peptides such as beta-amyloid(1-42) and synthetic apolipoproteinE
      peptides. The myristoylated alanine-rich C kinase substrate (MARCKS) protein is a
      major substrate of protein kinase C and is highly expressed in the developing and
      adult brain. The ability of a 25-amino acid synthetic MARCKS peptide, derived
      from the effector domain (ED), to modulate nAChR activity was tested. To
      determine the effects of the MARCKS ED peptide on nAChR function, receptors were
      expressed in Xenopus laevis oocytes, and two-electrode voltage-clamp experiments
      were performed. The MARCKS ED peptide completely inhibited acetylcholine (ACh)
      evoked responses from alpha7 nAChRs in a dose-dependent manner, yielding an
      IC(50) value of 16 nM. Inhibition of ACh-induced responses was both activity- and
      voltage-independent. The MARCKS ED peptide was unable to block alpha-bungarotoxin
      binding. A MARCKS ED peptide in which four serine residues were replaced with
      aspartate residues was unable to inhibit alpha7 nAChR-mediated currents. The
      MARCKS ED peptide inhibited ACh-induced alpha4beta2 and alpha2beta2 responses,
      although with decreased potency. The effects of the MARCKS ED peptide on native
      nAChRs were tested using acutely isolated rat hippocampal slices. In hippocampal
      interneurons, the MARCKS ED peptide was able to block native alpha7 nAChRs in a
      dose-dependent manner. The MARCKS ED peptide represents a novel antagonist of
      neuronal nAChRs that has considerable utility as a research tool.

PMID- 18812492
TI  - Chronic benzodiazepine administration potentiates high voltage-activated calcium
      currents in hippocampal CA1 neurons.
AB  - Signs of physical dependence as a consequence of long-term drug use and a
      moderate abuse liability limit benzodiazepine clinical usefulness. Growing
      evidence suggests a role for voltage-gated calcium channel (VGCC) regulation in
      mediating a range of chronic drug effects from drug withdrawal phenomena to
      dependence on a variety of drugs of abuse. High voltage-activated (HVA) calcium
      currents were measured in whole-cell recordings from acutely isolated hippocampal
      CA1 neurons after a 1-week flurazepam (FZP) treatment that results in withdrawal
      anxiety. An approximately 1.8-fold increase in Ca(2+) current density was
      detected immediately after and up to 2 days but not 3 or 4 days after drug
      withdrawal. Current density was unchanged after acute desalkyl-FZP treatment. A
      significant negative shift of the half-maximal potential of activation of HVA
      currents was also observed but steady-state inactivation remained unchanged. FZP
      and diazepam showed use- and concentration-dependent inhibition of Ca(2+)
      currents in hippocampal cultured cells following depolarizing trains (FZP, IC(50)
      = 1.8 microM; diazepam, IC(50) = 36 microM), pointing to an additional mechanism
      by which benzodiazepines modulate HVA Ca(2+) channels. Systemic preinjection of
      nimodipine (10 mg/kg), an L-type (L)-VGCC antagonist, prevented the
      benzodiazepine-induced increase in alpha-amino-3-hydroxy-5-methylisoxasole-4
      propionic acid receptor (AMPAR)-mediated miniature excitatory postsynaptic
      current in CA1 neurons 2 days after FZP withdrawal, suggesting that AMPAR
      potentiation, previously linked to withdrawal-anxiety may require enhanced L-VGCC
      mediated Ca(2+) influx. Taken together with prior work, these findings suggest
      that enhanced Ca(2+) entry through HVA Ca(2+) channels may contribute to
      hippocampal AMPAR plasticity and serve as a potential mechanism underlying
      benzodiazepine physical dependence.

PMID- 18812493
TI  - Inactivation of the maternal fragile X gene results in sensitization of GABAB
      receptor function in the offspring.
AB  - Fragile X syndrome is an X-linked disorder caused by the inactivation of the FMR1
      gene, with symptoms ranging from impaired cognitive functions to seizures,
      anxiety, sensory abnormalities, and hyperactivity. Although fragile X syndrome is
      considered a typical Mendelian disorder, we have recently reported that the
      environment, specifically the fmr1(+/-) or fmr1(-/-) [H or knockout (KO)]
      maternal environment, elicits on its own a partial fragile X-like phenotype and
      can contribute to the overall phenotype of fmr1(-/0) (KO) male offspring.
      Genetically fmr1(+/0) (WT) males born to H females (H(maternal) > WT(offspring)),
      similar to KO male offspring born to H and KO mothers (H > KO and KO > KO),
      exhibit locomotor hyperactivity. These mice also showed reduced D(2) autoreceptor
      function, indicating a possible diminished feedback inhibition of dopamine (DA)
      release in the nigrostriatal and mesolimbic systems. The GABAergic system also
      regulates DA release, in part via presynaptic GABA(B) receptors (Rs) located on
      midbrain dopaminergic neurons. Here, we show that the locomotor inhibitory effect
      of the GABA(B)R agonist baclofen [4-amino-3-(4-chlorophenyl)-butanoic acid] is
      enhanced in all progeny of mutant mothers (H > WT, H > KO, and KO > KO) compared
      with WT > WT mice, irrespective of their own genotype. However, increased
      sensitivity to baclofen was selective and limited to the locomotor response
      because the muscle-relaxant and sedative effects of the drug were not altered by
      the maternal environment. These data show that GABA(B)R sensitization,
      traditionally induced pharmacologically, can also be elicited by the fmr1
      deficient maternal environment.

PMID- 18812494
TI  - Improvement of endothelial function of the corpus cavernosum in apolipoprotein E
      knockout mice treated with irbesartan.
AB  - Angiotensin receptor blockers enhance endothelial function and are suggested to
      improve erectile function. The effects and underlying mechanisms of treatment
      with the angiotensin receptor blocker irbesartan on penile endothelial function
      in apolipoprotein E (ApoE)(-/-) mice were determined. Wild-type (C57/B6) and
      ApoE(-/-) mice were fed with a high-fat, cholesterol-rich diet for 7 weeks and
      treated with irbesartan (50 mg/kg . day) or hydralazine (250 mg/l). Vital
      parameters were measured with the tail-cuff method. Endothelial (aortic rings)
      and erectile function (corpora cavernosa) were assessed by pharmacological
      stimulation in an organ bath chamber. Oxidative stress and angiotensin receptor
      expression were determined. Blood pressure was significantly decreased in
      irbesartan- and hydralazine-treated ApoE(-/-) mice (p < 0.05) compared with
      controls and wild-type mice. Endothelial function of the aorta and corpus
      cavernosum was significantly impaired in ApoE(-/-) mice (p < 0.05) and could be
      restored by treatment with irbesartan (p < 0.05). Consistently, nitric oxide
      production of corpora cavernosa was impaired in ApoE(-/-) mice (p < 0.01), with a
      restoration in irbesartan- but not hydralazine-treated mice. Dihydroethidium
      stained sections and lipid peroxidase assay revealed a reduction of superoxide
      production in irbesartan (p < 0.05) compared with hydralazine-treated and control
      ApoE(-/-) mice. In summary, irbesartan improves penile endothelial function in
      ApoE(-/-) mice by reduction of vascular and cavernosal oxidative stress. This
      result emphasizes the beneficial effect of inhibition of the renin-angiotensin
      system even in terms of erectile function.

PMID- 18812496
TI  - Arabidopsis ARC6 coordinates the division machineries of the inner and outer
      chloroplast membranes through interaction with PDV2 in the intermembrane space.
AB  - Chloroplasts arose from a free-living cyanobacterial endosymbiont and divide by
      binary fission. Division involves the assembly and constriction of the
      endosymbiont-derived, tubulin-like FtsZ ring on the stromal surface of the inner
      envelope membrane and the host-derived, dynamin-like ARC5 ring on the cytosolic
      surface of the outer envelope membrane. Despite the identification of many
      proteins required for plastid division, the factors coordinating the internal and
      external division machineries are unknown. Here, we provide evidence that this
      coordination is mediated in Arabidopsis thaliana by an interaction between ARC6,
      an FtsZ assembly factor spanning the inner envelope membrane, and PDV2, an ARC5
      recruitment factor spanning the outer envelope membrane. ARC6 and PDV2 interact
      via their C-terminal domains in the intermembrane space, consistent with their in
      vivo topologies. ARC6 acts upstream of PDV2 to localize PDV2 (and hence ARC5) to
      the division site. We present a model whereby ARC6 relays information on stromal
      FtsZ ring positioning through PDV2 to the chloroplast surface to specify the site
      of ARC5 recruitment. Because orthologs of ARC6 occur in land plants, green algae,
      and cyanobacteria but PDV2 occurs only in land plants, the connection between
      ARC6 and PDV2 represents the evolution of a plant-specific adaptation to
      coordinate the assembly and activity of the endosymbiont- and host-derived
      plastid division components.

PMID- 18812497
TI  - Sexual and apomictic seed formation in Hieracium requires the plant polycomb
      group gene FERTILIZATION INDEPENDENT ENDOSPERM.
AB  - A Polycomb-Group (PcG) complex, FERTILIZATION INDEPENDENT SEED (FIS), represses
      endosperm development in Arabidopsis thaliana until fertilization occurs. The
      Hieracium genus contains apomictic species that form viable seeds asexually. To
      investigate FIS function during apomictic seed formation, FERTILIZATION
      INDEPENDENT ENDOSPERM (FIE), encoding a WD-repeat member of the FIS complex, was
      isolated and downregulated in sexual and apomictic Hieracium species. General
      downregulation led to defects in leaf and seed development, consistent with a
      role in developmental transitions and cell fate. PcG-like activity of Hieracium
      FIE was also supported by its interaction in vitro with the Arabidopsis CURLY
      LEAF PcG protein. By contrast, specific downregulation of FIE in developing seeds
      of sexual Hieracium did not result in autonomous endosperm proliferation but led
      to seed abortion after cross-pollination. Furthermore, in apomictic Hieracium,
      specific FIE downregulation inhibited autonomous embryo and endosperm initiation,
      and most autonomous seeds displayed defective embryo and endosperm growth.
      Therefore, FIE is required for both apomictic and fertilization-induced seed
      initiation in Hieracium. Since Hieracium FIE failed to interact with FIS class
      proteins in vitro, its partner proteins might differ from those in the FIS
      complex of Arabidopsis. These differences in protein interaction were attributed
      to structural modifications predicted from comparisons of Arabidopsis and
      Hieracium FIE molecular models.

PMID- 18812498
TI  - Biochemical characterization of Arabidopsis complexes containing CONSTITUTIVELY
      PHOTOMORPHOGENIC1 and SUPPRESSOR OF PHYA proteins in light control of plant
      development.
AB  - COP1 (for CONSTITUTIVELY PHOTOMORPHOGENIC1) and the four partially redundant SPA
      (for SUPPRESSOR OF PHYA) proteins work in concert to repress photomorphogenesis
      in Arabidopsis thaliana by targeting key transcription factors and phytochrome A
      for degradation via the 26S proteasome. Here, we report a detailed biochemical
      characterization of the SPA-COP1 complexes. The four endogenous SPA proteins can
      form stable complexes with COP1 in vivo regardless of light conditions but
      exhibit distinct expression profiles in different tissues and light conditions.
      The SPA proteins can self-associate or interact with each other, forming a
      heterogeneous group of SPA-COP1 complexes in which the exact SPA protein
      compositions vary depending on the abundance of individual SPA proteins. The four
      SPA proteins could be divided into two functional groups depending on their
      interaction affinities, their regulation of ELONGATED HYPOCOTYL5 degradation, and
      their opposite effects on COP1 protein accumulation. Loss-of-function mutations
      in a predominant SPA protein may cause a significant reduction in the overall SPA
      COP1 E3 ligase activity, resulting in a partial constitutive photomorphogenic
      phenotype. This study thus provides an in-depth biochemical view of the SPA-COP1
      E3 ligase complexes and offers new insights into the molecular basis for their
      distinct roles in the light control of plant development.

PMID- 18812499
TI  - Reinvigorating the concept of situation in social psychology.
AB  - The concept of situation has a long and venerable history in social psychology.
      The author argues that recent approaches to the concept of situation have
      confused certain important elements. Herein, the author proposes that attention
      to three of these elements will reinvigorate the concept of situation in social
      psychology: (a) that the analysis of situations should begin with their objective
      features; (b) that situations should be conceptualized as affordances; and (c)
      that the interpersonal core of situations, in particular the extent to which they
      are influenced by relationships, is the proper and most profitable focus for
      social psychology. These elements are consistent with recent developments in the
      study of situated social cognition and may help better define social psychology's
      position within the sciences.

PMID- 18812500
TI  - Contradictory saltation height measurements and unphysical assumptions.

PMID- 18812501
TI  - The stem rust resistance gene Rpg5 encodes a protein with nucleotide-binding
      site, leucine-rich, and protein kinase domains.
AB  - We isolated the barley stem rust resistance genes Rpg5 and rpg4 by map-based
      cloning. These genes are colocalized on a 70-kb genomic region that was delimited
      by recombination. The Rpg5 gene consists of an unusual structure encoding three
      typical plant disease resistance protein domains: nucleotide-binding site,
      leucine-rich repeat, and serine threonine protein kinase. The predicted RPG5
      protein has two putative transmembrane sites possibly involved in membrane
      binding. The gene is expressed at low but detectable levels. Posttranscriptional
      gene silencing using VIGS resulted in a compatible reaction with a normally
      incompatible stem rust pathogen. Allele sequencing also validated the candidate
      Rpg5 gene. Allele and recombinant sequencing suggested that the probable rpg4
      gene encoded an actin depolymerizing factor-like protein. Involvement of actin
      depolymerizing factor genes in nonhost resistance has been documented, but
      discovery of their role in gene-for-gene interaction would be novel and needs to
      be further substantiated.

PMID- 18812502
TI  - Navigating from hippocampus to parietal cortex.
AB  - The navigational system of the mammalian cortex comprises a number of interacting
      brain regions. Grid cells in the medial entorhinal cortex and place cells in the
      hippocampus are thought to participate in the formation of a dynamic
      representation of the animal's current location, and these cells are presumably
      critical for storing the representation in memory. To traverse the environment,
      animals must be able to translate coordinate information from spatial maps in the
      entorhinal cortex and hippocampus into body-centered representations that can be
      used to direct locomotion. How this is done remains an enigma. We propose that
      the posterior parietal cortex is critical for this transformation.

PMID- 18812503
TI  - T antigen mutations are a human tumor-specific signature for Merkel cell
      polyomavirus.
AB  - Merkel cell polyomavirus (MCV) is a virus discovered in our laboratory at the
      University of Pittsburgh that is monoclonally integrated into the genome of
      approximately 80% of human Merkel cell carcinomas (MCCs). Transcript mapping was
      performed to show that MCV expresses transcripts in MCCs similar to large T (LT),
      small T (ST), and 17kT transcripts of SV40. Nine MCC tumor-derived LT genomic
      sequences have been examined, and all were found to harbor mutations prematurely
      truncating the MCV LT helicase. In contrast, four presumed episomal viruses from
      nontumor sources did not possess this T antigen signature mutation. Using
      coimmunoprecipitation and origin replication assays, we show that tumor-derived
      virus mutations do not affect retinoblastoma tumor suppressor protein (Rb)
      binding by LT but do eliminate viral DNA replication capacity. Identification of
      an MCC cell line (MKL-1) having monoclonal MCV integration and the signature LT
      mutation allowed us to functionally test both tumor-derived and wild type (WT) T
      antigens. Only WT LT expression activates replication of integrated MCV DNA in
      MKL-1 cells. Our findings suggest that MCV-positive MCC tumor cells undergo
      selection for LT mutations to prevent autoactivation of integrated virus
      replication that would be detrimental to cell survival. Because these mutations
      render the virus replication-incompetent, MCV is not a "passenger virus" that
      secondarily infects MCC tumors.

PMID- 18812504
TI  - A polymicrobial perspective of pulmonary infections exposes an enigmatic pathogen
      in cystic fibrosis patients.
AB  - Lung disease is the leading cause of morbidity and mortality in cystic fibrosis
      (CF) patients. A modest number of bacterial pathogens have been correlated with
      pulmonary function decline; however, microbiological and molecular evidence
      suggests that CF airway infection is polymicrobial. To obtain a more complete
      assessment of the microbial community composition and dynamics, we undertook a
      longitudinal study by using culture-independent and microbiological approaches.
      In the process, we demonstrated that within complex and dynamic communities, the
      Streptococcus milleri group (SMG) can establish chronic pulmonary infections and
      at the onset of 39% of acute pulmonary exacerbations, SMG is the numerically
      dominant pathogen. We report the comprehensive polymicrobial community dynamics
      of a CF lung infection in a clinically relevant context. If a given organism,
      such as Pseudomonas aeruginosa, becomes resistant to antibiotic therapy, an
      alternative treatment avenue may mediate the desired clinical response by
      effectively managing the composition of the microbial community.

PMID- 18812505
TI  - Superoxide anions regulate TORC1 and its ability to bind Fpr1:rapamycin complex.
AB  - The small natural product rapamycin, when bound to FKBP12, is a potent inhibitor
      of an evolutionarily conserved Target of Rapamycin Complex 1 (TORC1), which plays
      a central role in mediating cellular response to nutrient availability. Given the
      prominent role of TORC1 in cell growth and proliferation, clinical trials have
      explored the possibility of using rapamycin as an anticancer agent.
      Unfortunately, the percentage of patients responding favorably has been low,
      intensifying the need to find biomarkers able to predict rapamycin sensitivity or
      resistance. In this study, we elucidate the molecular mechanism underlying
      partial rapamycin resistance in yeast. Using the yeast deletion collection, we
      identified 15 deletion strains leading to partial rapamycin resistance. Among
      these were Cu/Zn-superoxide dismutase Sod1, copper transporter Ctr1, and copper
      chaperone Lys7, suggesting a role for oxidative stress in rapamycin resistance.
      Further analysis revealed that all 15 strains exhibit elevated levels of
      superoxide anions, and we show that elevated levels of reactive oxygen species
      specifically modify TORC1 such that it is no longer able to fully bind
      FKBP12:rapamycin. Therefore, elevated oxidative stress modifies TORC1 and
      prevents its binding to the FKBP12:rapamycin complex, ultimately leading to
      rapamycin resistance. These results warrant an examination into whether similar
      reasons explain rapamycin resistance observed in various clinical samples.

PMID- 18812506
TI  - Circadian glucose homeostasis requires compensatory interference between brain
      and liver clocks.

PMID- 18812507
TI  - Non-cell-autonomous control of vascular stem cell fate by a CLE peptide/receptor
      system.
AB  - Land plants evolved a long-distance transport system of water and nutrients
      composed of the xylem and phloem, both of which are generated from the procambium
      and cambium-comprising vascular stem cells. However, little is known about the
      molecular mechanism of cell communication governing xylem-phloem patterning.
      Here, we show that a dodecapeptide (HEVHypSGHypNPISN; Hyp, 4-hydroxyproline),
      TDIF (tracheary element differentiation inhibitory factor), is secreted from the
      phloem and suppresses the differentiation of vascular stem cells into xylem cells
      through a leucine-rich repeat receptor-like kinase (LRR-RLK). TDIF binds in vitro
      specifically to the LRR-RLK, designated TDR (putative TDIF receptor), whose
      expression is restricted to procambial cells. However, the combined analysis of
      TDIF with a specific antibody and the expression profiles of the promoters of two
      genes encoding TDIF revealed that TDIF is synthesized mainly in, and secreted
      from, the phloem and its neighboring cells. The observation that TDIF is capable
      of promoting proliferation of procambial cells while suppressing xylem
      differentiation suggests that this small peptide functions as a phloem-derived,
      non-cell-autonomous signal that controls stem cell fate in the procambium. Our
      results indicate that we have discovered a cell communication system governing
      phloem-xylem cross-talk.

PMID- 18812508
TI  - The genome of Cyanothece 51142, a unicellular diazotrophic cyanobacterium
      important in the marine nitrogen cycle.
AB  - Unicellular cyanobacteria have recently been recognized for their contributions
      to nitrogen fixation in marine environments, a function previously thought to be
      filled mainly by filamentous cyanobacteria such as Trichodesmium. To begin a
      systems level analysis of the physiology of the unicellular N(2)-fixing microbes,
      we have sequenced to completion the genome of Cyanothece sp. ATCC 51142, the
      first such organism. Cyanothece 51142 performs oxygenic photosynthesis and
      nitrogen fixation, separating these two incompatible processes temporally within
      the same cell, while concomitantly accumulating metabolic products in inclusion
      bodies that are later mobilized as part of a robust diurnal cycle. The 5,460,377
      bp Cyanothece 51142 genome has a unique arrangement of one large circular
      chromosome, four small plasmids, and one linear chromosome, the first report of a
      linear element in the genome of a photosynthetic bacterium. On the 429,701-bp
      linear chromosome is a cluster of genes for enzymes involved in pyruvate
      metabolism, suggesting an important role for the linear chromosome in
      fermentative processes. The annotation of the genome was significantly aided by
      simultaneous global proteomic studies of this organism. Compared with other
      nitrogen-fixing cyanobacteria, Cyanothece 51142 contains the largest intact
      contiguous cluster of nitrogen fixation-related genes. We discuss the
      implications of such an organization on the regulation of nitrogen fixation. The
      genome sequence provides important information regarding the ability of
      Cyanothece 51142 to accomplish metabolic compartmentalization and energy storage,
      as well as how a unicellular bacterium balances multiple, often incompatible,
      processes in a single cell.

PMID- 18812509
TI  - Mutational analysis of the neurexin/neuroligin complex reveals essential and
      regulatory components.
AB  - Neurexins are cell-surface molecules that bind neuroligins to form a
      heterophilic, Ca(2+)-dependent complex at central synapses. This transsynaptic
      complex is required for efficient neurotransmission and is involved in the
      formation of synaptic contacts. In addition, both molecules have been identified
      as candidate genes for autism. Here we performed mutagenesis experiments to probe
      for essential components of the neurexin/neuroligin binding interface at the
      single-amino acid level. We found that in neurexins the contact area is sharply
      delineated and consists of hydrophobic residues of the LNS domain that surround a
      Ca(2+) binding pocket. Point mutations that changed electrostatic and shape
      properties leave Ca(2+) coordination intact but completely inhibit neuroligin
      binding, whereas alternative splicing in alpha- and beta-neurexins and in
      neuroligins has a weaker effect on complex formation. In neuroligins, the contact
      area appears less distinct because exchange of a more distant aspartate
      completely abolished binding to neurexin but many mutations of predicted
      interface residues had no strong effect on binding. Together with calculations of
      energy terms for presumed interface hot spots that complement and extend our
      mutagenesis and recent crystal structure data, this study presents a
      comprehensive structural basis for the complex formation of neurexins and
      neuroligins and their transsynaptic signaling between neurons.

PMID- 18812510
TI  - Mitochondrial complex I inhibition is not required for dopaminergic neuron death
      induced by rotenone, MPP+, or paraquat.
AB  - Inhibition of mitochondrial complex I is one of the leading hypotheses for
      dopaminergic neuron death associated with Parkinson's disease (PD). To test this
      hypothesis genetically, we used a mouse strain lacking functional Ndufs4, a gene
      encoding a subunit required for complete assembly and function of complex I.
      Deletion of the Ndufs4 gene abolished complex I activity in midbrain
      mesencephalic neurons cultured from embryonic day (E) 14 mice, but did not affect
      the survival of dopaminergic neurons in culture. Although dopaminergic neurons
      were more sensitive than other neurons in these cultures to cell death induced by
      rotenone, MPP(+), or paraquat treatments, the absence of complex I activity did
      not protect the dopaminergic neurons, as would be expected if these compounds act
      by inhibiting complex 1. In fact, the dopaminergic neurons were more sensitive to
      rotenone. These data suggest that dopaminergic neuron death induced by treatment
      with rotenone, MPP(+), or paraquat is independent of complex I inhibition.

PMID- 18812511
TI  - Is getting older all that rewarding?

PMID- 18812512
TI  - Directed evolution of a G protein-coupled receptor for expression, stability, and
      binding selectivity.
AB  - We outline a powerful method for the directed evolution of integral membrane
      proteins in the inner membrane of Escherichia coli. For a mammalian G protein
      coupled receptor, we arrived at a sequence with an order-of-magnitude increase in
      functional expression that still retains the biochemical properties of wild type.
      This mutant also shows enhanced heterologous expression in eukaryotes (12-fold in
      Pichia pastoris and 3-fold in HEK293T cells) and greater stability when
      solubilized and purified, indicating that the biophysical properties of the
      protein had been under the pressure of selection. These improvements arise from
      multiple small contributions, which would be difficult to assemble by rational
      design. In a second screen, we rapidly pinpointed a single amino acid
      substitution in wild type that abolishes antagonist binding while retaining
      agonist-binding affinity. These approaches may alleviate existing bottlenecks in
      structural studies of these targets by providing sufficient quantities of stable
      variants in defined conformational states.

PMID- 18812513
TI  - Modeling the chemotactic response of Escherichia coli to time-varying stimuli.
AB  - In their natural environment, cells need to extract useful information from
      complex temporal signals that vary over a wide range of intensities and time
      scales. Here, we study how such signals are processed by Escherichia coli during
      chemotaxis by developing a general theoretical model based on receptor adaptation
      and receptor-receptor cooperativity. Measured responses to various monotonic,
      oscillatory, and impulsive stimuli are all explained consistently by the
      underlying adaptation kinetics within this model. For exponential ramp signals,
      an analytical solution is discovered that reveals a remarkable connection between
      the dependence of kinase activity on the exponential ramp rate and the receptor
      methylation rate function. For exponentiated sine-wave signals, spectral analysis
      shows that the chemotaxis pathway acts as a lowpass filter for the derivative of
      the signal with the cutoff frequency determined by an intrinsic adaptation time
      scale. For large step stimuli, we find that the recovery time is determined by
      the constant maximum methylation rate, which provides a natural explanation for
      the observed recovery time additivity. Our model provides a quantitative system
      level description of the chemotaxis signaling pathway and can be used to predict
      E. coli chemotaxis responses to arbitrary temporal signals. This model of the
      receptor system reveals the molecular origin of Weber's law in bacterial
      chemotaxis. We further identify additional constraints required to account for
      the related observation that the output of this pathway is constant under
      exponential ramp stimuli, a feature that we call "logarithmic tracking."

PMID- 18812514
TI  - A channel connecting the mother cell and forespore during bacterial endospore
      formation.
AB  - At an early stage during Bacillus subtilis endospore development the bacterium
      divides asymmetrically to produce two daughter cells. The smaller cell
      (forespore) differentiates into the endospore, while the larger cell (mother
      cell) becomes a terminally differentiated cell that nurtures the developing
      forespore. During development the mother cell engulfs the forespore to produce a
      protoplast, surrounded by two bilayer membranes, which separate it from the
      cytoplasm of the mother cell. The activation of sigma(G), which drives late gene
      expression in the forespore, follows forespore engulfment and requires expression
      of the spoIIIA locus in the mother cell. One of the spoIIIA-encoded proteins
      SpoIIIAH is targeted specifically to the membrane surrounding the forespore,
      through an interaction of its C-terminal extracellular domain with the C-terminal
      extracellular domain of the forespore membrane protein SpoIIQ. We identified a
      homologous relationship between the C-terminal domain of SpoIIIAH and the
      YscJ/FliF protein family, members of which form multimeric rings involved in type
      III secretion systems and flagella. If SpoIIIAH forms a similar ring structure,
      it may also form a channel between the mother cell and forespore membranes. To
      test this hypothesis we developed a compartmentalized biotinylation assay, which
      we used to show that the C-terminal extracellular domain of SpoIIIAH is
      accessible to enzymatic modification from the forespore cytoplasm. These and
      other results lead us to suggest that SpoIIIAH forms part of a channel between
      the forespore and mother cell that is required for the activation of sigma(G).

PMID- 18812515
TI  - The crystal structure of MexR from Pseudomonas aeruginosa in complex with its
      antirepressor ArmR.
AB  - The intrinsic antimicrobial resistance of the opportunistic human pathogen
      Pseudomonas aeruginosa is compounded in mutant strains that overexpress multidrug
      efflux pumps such as the prominent drug-proton antiporter, MexAB-OprM. The
      primary regulator of the mexAB-oprM operon is the MarR family repressor, MexR. An
      additional repressor, NalC, also regulates mexAB-oprM by controlling expression
      of ArmR, an antirepressor peptide that is hypothesized to prevent the binding of
      MexR to its cognate DNA operator via an allosteric protein-peptide interaction.
      To better understand how ArmR modulates MexR, we determined the MexR-binding
      region of ArmR as its C-terminal 25 residues and solved the crystal structure of
      MexR in a 2:1 complex with this ArmR fragment at 1.8 A resolution. This structure
      reveals that the C-terminal residues of ArmR form a kinked alpha-helix, which
      occupies a pseudosymmetrical and largely hydrophobic binding cavity located at
      the centre of the MexR dimer. Although the ArmR-binding cavity partially overlaps
      with the small molecule effector-binding sites of other MarR family members, it
      possesses a larger and more complex binding surface to accommodate the greater
      size and specific physicochemical properties of a peptide effector. Comparison
      with the structure of apo-MexR reveals that ArmR stabilizes a dramatic
      conformational change that is incompatible with DNA-binding. Thus, this work
      defines the structural mechanism by which ArmR allosterically derepresses MexR
      controlled gene expression in P. aeruginosa and reveals important insights into
      the regulation of multidrug resistance.

PMID- 18812516
TI  - A search for conserved sequences in coding regions reveals that the let-7
      microRNA targets Dicer within its coding sequence.
AB  - Recognition sites for microRNAs (miRNAs) have been reported to be located in the
      3' untranslated regions of transcripts. In a computational screen for highly
      conserved motifs within coding regions, we found an excess of sequences conserved
      at the nucleotide level within coding regions in the human genome, the highest
      scoring of which are enriched for miRNA target sequences. To validate our
      results, we experimentally demonstrated that the let-7 miRNA directly targets the
      miRNA-processing enzyme Dicer within its coding sequence, thus establishing a
      mechanism for a miRNA/Dicer autoregulatory negative feedback loop. We also found
      computational evidence to suggest that miRNA target sites in coding regions and
      3' UTRs may differ in mechanism. This work demonstrates that miRNAs can directly
      target transcripts within their coding region in animals, and it suggests that a
      complete search for the regulatory targets of miRNAs should be expanded to
      include genes with recognition sites within their coding regions. As more genomes
      are sequenced, the methodological approach that we used for identifying motifs
      with high sequence conservation will be increasingly valuable for detecting
      functional sequence motifs within coding regions.

PMID- 18812517
TI  - Engineering G protein-coupled receptor expression in bacteria.

PMID- 18812518
TI  - Predators avoiding predation.

PMID- 18812519
TI  - Promyelocytic leukemia protein induces apoptosis due to caspase-8 activation via
      the repression of NFkappaB activation in glioblastoma.
AB  - Promyelocytic leukemia (PML) protein plays an essential role in the induction of
      apoptosis; its expression is reduced in various cancers. As the functional roles
      of PML in glioblastoma multiforme (GBM) have not been clarified, we assessed the
      expression of PML protein in GBM tissues and explored the mechanisms of PML
      regulated cell death in GBM cells. We examined the PML mRNA level and the
      expression of PML protein in surgical GBM specimens. PML-regulated apoptotic
      mechanisms in GBM cells transfected with plasmids expressing the PML gene were
      examined. The protein expression of PML was significantly lower in GBM than in
      non-neoplastic tissues; approximately 10% of GBM tissues were PML-null. The PML
      mRNA levels were similar in both tissue types. The overexpression of PML
      activated caspase-8 and induced apoptosis in GBM cells. In these cells, PML
      decreased the expression of transactivated forms of NFkappaB/p65, and c-FLIP gene
      expression was suppressed. Therefore, PML-induced apoptosis resulted from the
      suppression of the transcriptional activity of NFkappaB/p65. PML overexpression
      decreased phosphorylated IkappaBalpha and nuclear NFkappaB/p65 and increased the
      expression of the suppressor of cytokine signaling (SOCS-1). A proteasome
      inhibitor blocked the reduction of activated p65 by PML. The reduction of PML is
      associated with the pathogenesis of GBM. PML induces caspase-8-dependent
      apoptosis via the repression of NFkappaB activation by which PML facilitates the
      proteasomal degradation of activated p65 and the sequestration of p65 with
      IkappaBalpha in the cytoplasm. This novel mechanism of PML-regulated apoptosis
      may represent a therapeutic target for GBM.

PMID- 18812520
TI  - The L84F polymorphic variant of human O6-methylguanine-DNA methyltransferase
      alters stability in U87MG glioma cells but not temozolomide sensitivity.
AB  - First-line therapy for patients with glioblastoma multiforme includes treatment
      with radiation and temozolomide (TMZ), an oral DNA alkylating chemotherapy.
      Sensitivity of glioma cells to TMZ is dependent on the level of cellular O(6)
      methylguanine-DNA methyltransferase (MGMT) repair activity. Several common coding
      region polymorphisms in the MGMT gene (L84F and the linked pair I143V/K178R)
      modify functional characteristics of MGMT and cancer risk. To determine whether
      these polymorphic changes influence the ability of MGMT to protect glioma cells
      from TMZ, we stably overexpressed enhanced green fluorescent protein (eGFP)
      tagged MGMT constructs in U87MG glioma cells. We confirmed that the wild-type
      (WT) eGFP-MGMT protein is properly localized within the nucleus and found that
      L84F, I143V/K178R, and L84F/I143V/K178R eGFP-MGMT variants exhibited nuclear
      localization patterns indistinguishable from WT. Using MTT [3-(4,5-dimethyl-2
      thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide] proliferation and clonogenic
      survival assays, we confirmed that WT cells expressing eGFP-MGMT are resistant to
      TMZ treatment compared with control U87MG cells, and that each of the polymorphic
      eGFP-MGMT variants confers similar resistance to TMZ. However, upon exposure to
      O(6)-benzylguanine (O(6)-BG), a synthetic MGMT inhibitor, the L84F and
      L84F/I143V/K178R variants were degraded more rapidly than WT or I143V/K178R in a
      proteasome-dependent manner. Despite the increased O(6)-BG- stimulated protein
      turnover caused by the L84F alteration, cells expressing L84F eGFP-MGMT did not
      exhibit altered sensitivity to the combination of O(6)-BG and TMZ compared with
      WT cells. In conclusion, we demonstrated that the L84F polymorphic variant has
      altered protein turnover without modifying sensitivity of U87MG cells to TMZ or
      combined TMZ and O(6)-BG. These findings may provide a clue to determining the
      clinical significance of MGMT coding-region polymorphisms.

PMID- 18812522
TI  - The cover. Head of a woman.

PMID- 18812521
TI  - EGFRvIII expression and PTEN loss synergistically induce chromosomal instability
      and glial tumors.
AB  - Glioblastomas often show activation of epidermal growth factor receptor (EGFR)
      and loss of PTEN (phosphatase and tensin homolog deleted on chromosome 10) tumor
      suppressor, but it is not known if these two genetic lesions act together to
      transform cells. To answer this question, we infected PTEN-/- neural precursor
      cells with a retrovirus encoding EGFRvIII, which is a constitutively activated
      receptor. EGFRvIII PTEN-/- cells formed highly mitotic tumors with nuclear
      pleomorphism, necrotic areas, and glioblastoma markers. The transformed cells
      showed increased cell proliferation, centrosome amplification, colony formation
      in soft agar, self-renewal, expression of the stem cell marker CD133, and
      resistance to oxidative stress and ionizing radiation. The RAS/mitogen-activated
      protein kinase (ERK) and phosphoinositide 3-kinase/protein kinase B (PI3K/Akt)
      pathways were activated, and checkpoint kinase 1 (Chk1), the DNA damage
      regulator, was phosphorylated at S280 by Akt, suppressing Chk1 phosphorylation at
      S345 in response to ionizing irradiation. The PTEN-/- cells showed low levels of
      DNA damage in the absence of irradiation, which was increased by EGFRvIII
      expression. Finally, secondary changes occurred during tumor growth in mice.
      Cells from these tumors showed decreased tumor latencies and additional
      chromosomal aberrations. Most of these tumor lines showed translocations of mouse
      chromosome 15. Intracranial injections of one of these lines led to invasive,
      glial fibrillary acidic protein-positive, nestin-positive tumors. These results
      provide a molecular basis for the occurrence of these two genetic lesions in
      brain tumors and point to a role in induction of genomic instability.

PMID- 18812523
TI  - A piece of my mind. Who's afraid of the empowered patient?

PMID- 18812524
TI  - Report urges addressing barriers to reimbursement for mental health care.

PMID- 18812525
TI  - Experts weigh pros and cons of screening and treatment for childhood obesity.

PMID- 18812526
TI  - Effect of folic acid and B vitamins on cardiovascular disease in women.

PMID- 18812527
TI  - Effect of folic acid and B vitamins on cardiovascular disease in women.

PMID- 18812528
TI  - Chemotherapy and radiotherapy for anal canal carcinoma.

PMID- 18812529
TI  - Effect of folic acid and B vitamins on cardiovascular disease in women.

PMID- 18812530
TI  - Off-label indications for medication use and the published literature.

PMID- 18812531
TI  - Low levels of awareness of pharmaceutical cost-assistance programs among inner
      city seniors.

PMID- 18812532
TI  - Prevalence of colon polyps detected by colonoscopy screening in asymptomatic
      black and white patients.
AB  - CONTEXT: Compared with white individuals, black men and women have a higher
      incidence and mortality from colorectal cancer and may develop cancer at a
      younger age. Colorectal cancer screening might be less effective in black
      individuals, if there are racial differences in the age-adjusted prevalence and
      location of cancer precursor lesions. OBJECTIVES: To determine and compare the
      prevalence rates and location of polyps sized more than 9 mm in diameter in
      asymptomatic black and white individuals who received colonoscopy screening.
      DESIGN, SETTING, AND PATIENTS: Colonoscopy data were prospectively collected from
      67 adult gastrointestinal practice sites in the United States using a
      computerized endoscopic report generator between January 1, 2004, and December
      31, 2005. Data were transmitted to a central data repository, where all
      asymptomatic white (n = 80 061) and black (n = 5464) patients who had received
      screening colonoscopy were identified. MAIN OUTCOME MEASURES: Prevalence and
      location of polyps sized more than 9 mm, adjusted for age, sex, and family
      history of colorectal cancer in a multivariate analysis. RESULTS: Both black men
      and women had a higher prevalence of polyps sized more than 9 mm in diameter
      compared with white men and women (422 [7.7%] vs 4964 [6.2%]; P < .001). Compared
      with white patients, the adjusted odds ratio (OR) for black men was 1.16 (95%
      confidence interval [CI], 1.01-1.34) and the adjusted OR for black women was 1.62
      (95% CI, 1.39-1.89). Black and white patients had a similar risk of proximal
      polyps sized more than 9 mm (OR, 1.13;95% CI, 0.93-1.38). However, in a
      subanalysis of patients older than 60 years, proximal polyps sized more than 9 mm
      were more likely prevalent in black men (P = .03) and women (P < .001) compared
      with white men and women. CONCLUSION: Compared with white individuals, black men
      and women undergoing screening colonoscopy have a higher risk of polyps sized
      more than 9 mm, and black individuals older than 60 years are more likely to have
      proximal polyps sized more than 9 mm.

PMID- 18812533
TI  - Regional variation in out-of-hospital cardiac arrest incidence and outcome.
AB  - CONTEXT: The health and policy implications of regional variation in incidence
      and outcome of out-of-hospital cardiac arrest remain to be determined. OBJECTIVE:
      To evaluate whether cardiac arrest incidence and outcome differ across geographic
      regions. DESIGN, SETTING, AND PATIENTS: Prospective observational study (the
      Resuscitation Outcomes Consortium) of all out-of-hospital cardiac arrests in 10
      North American sites (8 US and 2 Canadian) from May 1, 2006, to April 30, 2007,
      followed up to hospital discharge, and including data available as of June 28,
      2008. Cases (aged 0-108 years) were assessed by organized emergency medical
      services (EMS) personnel, did not have traumatic injury, and received attempts at
      external defibrillation or chest compressions or resuscitation was not attempted.
      Census data were used to determine rates adjusted for age and sex. MAIN OUTCOME
      MEASURES: Incidence rate, mortality rate, case-fatality rate, and survival to
      discharge for patients assessed or treated by EMS personnel or with an initial
      rhythm of ventricular fibrillation. RESULTS: Among the 10 sites, the total
      catchment population was 21.4 million, and there were 20,520 cardiac arrests. A
      total of 11,898 (58.0%) had resuscitation attempted; 2729 (22.9% of treated) had
      initial rhythm of ventricular fibrillation or ventricular tachycardia or rhythms
      that were shockable by an automated external defibrillator; and 954 (4.6% of
      total) were discharged alive. The median incidence of EMS-treated cardiac arrest
      across sites was 52.1 (interquartile range [IQR], 48.0-70.1) per 100,000
      population; survival ranged from 3.0% to 16.3%, with a median of 8.4% (IQR, 5.4%
      10.4%). Median ventricular fibrillation incidence was 12.6 (IQR, 10.6-5.2) per
      100,000 population; survival ranged from 7.7% to 39.9%, with a median of 22.0%
      (IQR, 15.0%-24.4%), with significant differences across sites for incidence and
      survival (P<.001). CONCLUSION: In this study involving 10 geographic regions in
      North America, there were significant and important regional differences in out
      of-hospital cardiac arrest incidence and outcome.

PMID- 18812534
TI  - Prehospital termination of resuscitation in cases of refractory out-of-hospital
      cardiac arrest.
AB  - CONTEXT: Identifying patients in the out-of-hospital setting who have no
      realistic hope of surviving an out-of-hospital cardiac arrest could enhance
      utilization of scarce health care resources. OBJECTIVE: To validate 2 out-of
      hospital termination-of-resuscitation rules developed by the Ontario Prehospital
      Life Support (OPALS) study group, one for use by responders providing basic life
      support (BLS) and the other for those providing advanced life support (ALS).
      DESIGN, SETTING, AND PATIENTS: Retrospective cohort study using surveillance data
      prospectively submitted by emergency medical systems and hospitals in 8 US cities
      to the Cardiac Arrest Registry to Enhance Survival (CARES) between October 1,
      2005, and April 30, 2008. Case patients were 7235 adults with out-of-hospital
      cardiac arrest; of these, 5505 met inclusion criteria. MAIN OUTCOME MEASURES:
      Specificity and positive predictive value of each termination-of-resuscitation
      rule for identifying patients who likely will not survive to hospital discharge.
      RESULTS: The overall rate of survival to hospital discharge was 7.1% (n = 392).
      Of 2592 patients (47.1%) who met BLS criteria for termination of resuscitation
      efforts, only 5 (0.2%) patients survived to hospital discharge. Of 1192 patients
      (21.7%) who met ALS criteria, none survived to hospital discharge. The BLS rule
      had a specificity of 0.987 (95% confidence interval [CI], 0.970-0.996) and a
      positive predictive value of 0.998 (95% CI, 0.996-0.999) for predicting lack of
      survival. The ALS rule had a specificity of 1.000 (95% CI, 0.991-1.000) and
      positive predictive value of 1.000 (95% CI, 0.997-1.000) for predicting lack of
      survival. CONCLUSION: In this validation study, the BLS and ALS termination-of
      resuscitation rules performed well in identifying patients with out-of-hospital
      cardiac arrest who have little or no chance of survival.

PMID- 18812535
TI  - Inhaled anticholinergics and risk of major adverse cardiovascular events in
      patients with chronic obstructive pulmonary disease: a systematic review and meta
      analysis.
AB  - CONTEXT: Inhaled anticholinergics (ipratropium bromide or tiotropium bromide) are
      widely used in patients with chronic obstructive pulmonary disease (COPD) but
      their effect on the risk of cardiovascular outcomes is unknown. OBJECTIVE: To
      ascertain the cardiovascular risks of inhaled anticholinergics, including
      cardiovascular death, myocardial infarction (MI), and stroke. DATA SOURCES:
      Systematic searches were conducted on March 19, 2008, of relevant articles in
      MEDLINE, the Cochrane Database of systematic reviews, regulatory authority Web
      sites in the United States and the United Kingdom, and manufacturers' trial
      registries with no date restrictions. STUDY SELECTION: Randomized controlled
      trials of any inhaled anticholinergic for treatment of COPD that had at least 30
      days of treatment and reported on cardiovascular events. DATA EXTRACTION: The
      primary outcome was a composite of cardiovascular death, MI, or stroke. The
      secondary outcome was all-cause mortality. Relative risks (RRs) were estimated
      using fixed-effects models and statistical heterogeneity was estimated with the
      I(2) statistic. DATA SYNTHESIS: After a detailed screening of 103 articles, 17
      trials enrolling 13,645 [corrected] patients were analyzed. Follow-up duration
      ranged from 6 weeks to 5 years. Cardiovascular death, MI, or stroke occurred in
      134 of 6984 [corrected] patients (1.9%) [corrected] receiving inhaled
      anticholinergics and 83 of 6661 [corrected] patients (1.2%) receiving control
      therapy (RR, 1.60 [corrected] [95% confidence interval {CI}, 1.22-2.10];
      [corrected] P < .001, I(2) = 0%). Among individual components of the primary end
      point, inhaled anticholinergics significantly increased the risk of MI (RR, 1.52
      [95% CI 1.04-2.22]; [corrected] P = .03, I(2) = 0%) and cardiovascular death (RR,
      1.92 [95% CI, 1.23-3.00]; P = .004, [corrected] I(2) = 0%) without a
      statistically significant increase in the risk of stroke (RR, 1.46 [95% CI, 0.81
      2.62]; P = .20, I(2) = 0%). All-cause mortality was reported in 146 [corrected]
      of the patients treated with inhaled anticholinergics (2.1%) and 108 [corrected]
      of the control patients (1.6%) (RR, 1.29 [95% CI, 1.00-1.65]; P = .05, I(2) = 0%)
      [corrected] A sensitivity analysis restricted to 6 [corrected] long-term trials
      (>6 months) confirmed the significantly increased risk of cardiovascular death,
      MI, or stroke (2.9% of patients treated with anticholinergics vs 1.8% of the
      control patients; RR, 1.73 [95% CI, 1.27-2.35]; [corrected] P < .001, I(2) = 0%).
      CONCLUSION: Inhaled anticholinergics are associated with a significantly
      increased risk of cardiovascular death, MI, or stroke among patients with COPD.

PMID- 18812536
TI  - Banning tobacco sales in pharmacies: the right prescription.

PMID- 18812537
TI  - Risks and benefits of importing prescription medications from lower-income
      countries.

PMID- 18812538
TI  - Ethical considerations for short-term experiences by trainees in global health.

PMID- 18812539
TI  - Colorectal cancer risk: black, white, or shades of gray?

PMID- 18812540
TI  - Surviving cardiac arrest: location, location, location.

PMID- 18812541
TI  - JAMA patient page. Colon polyps.

PMID- 18812542
TI  - ESAs further restricted, but debate continues.

PMID- 18812543
TI  - Expensive cancer drugs with modest benefit ignite debate over solutions.

PMID- 18812544
TI  - Cancer-killing viruses assist gene therapies.

PMID- 18812545
TI  - StatBite: Alcohol-related deaths from chronic causes among American Indians and
      Alaska Natives.

PMID- 18812546
TI  - Increasing breast cancer incidence in China: the numbers add up.

PMID- 18812547
TI  - Menopausal hormone therapy in BRCA1 mutation carriers: uncertainty and caution.

PMID- 18812548
TI  - Hormone therapy and the risk of breast cancer in BRCA1 mutation carriers.
AB  - BACKGROUND: Hormone therapy (HT) is commonly given to women to alleviate the
      climacteric symptoms associated with menopause. There is concern that this
      treatment may increase the risk of breast cancer. The potential association of HT
      and breast cancer risk is of particular interest to women who carry a mutation in
      BRCA1 because they face a high lifetime risk of breast cancer and because many of
      these women take HT after undergoing prophylactic surgical oophorectomy at a
      young age. METHODS: We conducted a matched case-control study of 472
      postmenopausal women with a BRCA1 mutation to examine whether or not the use of
      HT is associated with subsequent risk of breast cancer. Breast cancer case
      patients and control subjects were matched with respect to age, age at menopause,
      and type of menopause (surgical or natural). Odds ratios (ORs) and 95% confidence
      intervals (CIs) were estimated with conditional logistic regression. Statistical
      tests were two-sided. RESULTS: In this group of BRCA1 mutation carriers, the
      adjusted OR for breast cancer associated with ever use of HT compared with never
      use was 0.58 (95% CI = 0.35 to 0.96; P = .03). In analyses by type of HT, an
      inverse association with breast cancer risk was observed with use of estrogen
      only (OR = 0.51, 95% CI = 0.27 to 0.98; P = .04); the association with use of
      estrogen plus progesterone was not statistically significant (OR = 0.66, 95% CI =
      0.34 to 1.27; P = .21). CONCLUSION: Among postmenopausal women with a BRCA1
      mutation, HT use was not associated with increased risk of breast cancer; indeed,
      in this population, it was associated with a decreased risk.

PMID- 18812549
TI  - Cause-specific late mortality among 5-year survivors of childhood cancer: the
      Childhood Cancer Survivor Study.
AB  - BACKGROUND: The proportion of pediatric and adolescent cancer patients surviving
      5 years has increased during the past four decades. This growing population of
      survivors remains at risk for disease- and treatment-associated late mortality.
      METHODS: A total of 20 483 five-year survivors of childhood and adolescent cancer
      diagnosed between January 1, 1970, and December 31, 1986, and enrolled in the
      Childhood Cancer Survivor Study (CCSS) were included in a National Death Index
      search for deaths occurring between January 1, 1979, and December 31, 2002.
      Treatment information was abstracted from primary medical records. Survival
      probabilities, standardized mortality ratios (SMRs), and absolute excess risks
      were calculated for overall and cause-specific deaths. Diagnosis- and sex
      specific survival probabilities were estimated by the product-limit method. All
      statistical tests were two-sided. RESULTS: Among the CCSS cohort, 2821 (13.8%) 5
      year survivors had died by the end of the follow-up period. The cause of death
      was obtained for 2534 individuals, with 57.5% of deaths attributed to recurrent
      disease. Estimated probability of survival 30 years from diagnosis was 82%. When
      compared with the US population, the absolute excess risk of death from any cause
      was 7.36 deaths per 1000 person-years. The overall SMR was 8.4 (95% confidence
      interval [CI] = 8.0 to 8.7). Increases in cause-specific mortality were seen for
      deaths due to subsequent malignancy (SMR = 15.2, 95% CI = 13.9 to 16.6) and
      cardiac (SMR = 7.0, 95% CI = 5.9 to 8.2), pulmonary (SMR = 8.8, 95% CI = 6.8 to
      11.2), and other medical (SMR = 2.6, 95% CI = 2.3 to 3.0) causes. At 20 years of
      follow-up (25 years after first cancer diagnosis), the death rate due to a
      subsequent malignancy exceeded that due to all other causes. CONCLUSION: Our
      extended follow-up of 5-year survivors of pediatric and adolescent cancer
      indicates that excess mortality persists long after diagnosis. Continued
      observation is needed to further define lifetime risk and to determine the
      potential contribution of chronic health conditions and modifiable health
      behaviors.

PMID- 18812550
TI  - Outcome prediction for estrogen receptor-positive breast cancer based on
      postneoadjuvant endocrine therapy tumor characteristics.
AB  - BACKGROUND: Understanding how tumor response is related to relapse risk would
      help clinicians make decisions about additional treatment options for patients
      who have received neoadjuvant endocrine treatment for estrogen receptor-positive
      (ER+) breast cancer. METHODS: Tumors from 228 postmenopausal women with confirmed
      ER+ stage 2 and 3 breast cancers in the P024 neoadjuvant endocrine therapy trial,
      which compared letrozole and tamoxifen for 4 months before surgery, were analyzed
      for posttreatment ER status, Ki67 proliferation index, histological grade,
      pathological tumor size, node status, and treatment response. Cox proportional
      hazards were used to identify factors associated with relapse-free survival (RFS)
      and breast cancer-specific survival (BCSS) in 158 women. A preoperative endocrine
      prognostic index (PEPI) for RFS was developed from these data and validated in an
      independent study of 203 postmenopausal women in the IMPACT trial, which compared
      treatment with anastrozole, tamoxifen, or the combination 3 months before
      surgery. Statistical tests were two-sided. RESULTS: Median follow-up in P024 was
      61.2 months. Patients with confirmed baseline ER+ clinical stage 2 and 3 tumors
      that were downstaged to stage 1 or 0 at surgery had 100% RFS (compared with
      higher stages, P < .001). Multivariable testing of posttreatment tumor
      characteristics revealed that pathological tumor size, node status, Ki67 level,
      and ER status were independently associated with both RFS and BCSS. The PEPI
      model based on these factors predicted RFS in the IMPACT trial (P = .002).
      CONCLUSIONS: Breast cancer patients with pathological stage 1 or 0 disease after
      neoadjuvant endocrine therapy and a low-risk biomarker profile in the surgical
      specimen (PEPI score 0) have an extremely low risk of relapse and are therefore
      unlikely to benefit from adjuvant chemotherapy.

PMID- 18812551
TI  - A genetically enhanced anaerobic bacterium for oncopathic therapy of pancreatic
      cancer.
AB  - BACKGROUND: A major obstacle in treatment of solid tumors is the inefficient
      delivery of therapeutic agents to the hypoxic cores. Hypoxia offers the potential
      for anaerobic bacteria colonization and tumor destruction by the bacteria, and
      dormant spores of wild-type Clostridium perfringens (Cp) germinate and
      proliferate within the hypoxic cores of pancreatic tumors in mice. However, the
      oncopathic effects of Cp were limited by host inflammatory responses and by Cp's
      residual tolerance to oxygen, which caused toxic effects in animals. METHODS:
      Recombinant Cp strains in which superoxide dismutase, a major oxygen tolerance
      gene, was deleted (Cp/sod(-)) were constructed to enhance its selective growth in
      tumors. In addition, Panton-Valentine Leukocidin (PVL), an inflammation
      suppressing gene from Staphylococcus aureus, was inserted into the Cp/sod(-)
      genome to enhance its oncopathic potency. The ability of the recombinant Cp
      strains to kill tumors was investigated in C57/BL6 mice bearing murine PANC02
      tumors. Systemic and organ toxic effects were assessed by monitoring serum
      chemistries and histopathological examination. Statistical tests were two-sided.
      RESULTS: Cp/sod(-) showed reduced toxic effects compared with wild-type Cp when
      spores were administered intravenously into PANC02 tumor-bearing mice. Mice
      treated with Cp/sod(-)/PVL spores demonstrated a reduction in neutrophils and
      macrophages in tumors, logarithmically elevated growth of intratumoral bacteria,
      enhanced tumor necrosis, and substantially prolonged survival without apparent
      systemic and organ toxic effects, compared with mice treated with both wild-type
      Cp and Cp/sod(-) spores. Accordingly, 47% of Cp/sod(-)/PVL-treated mice (n = 15)
      achieved tumor-free survival for over 120 days, whereas all mice treated with
      Cp/sod(-) or phosphate-buffered saline (n = 10 per group) died within 50 days.
      The median survival for Cp/sod(-)/PVL-treated mice was 77 days (95% confidence
      interval [CI] = 45 to 120 days) and for Cp/sod(-)-treated mice was 30 days (95%
      CI = 23 to 36 days; P < .001). CONCLUSIONS: Cp/sod(-)/PVL provides a prototype
      for a novel class of oncopathic microbes that may have potential for the safe and
      effective treatment of pancreatic cancer and other poorly vascularized tumors.

PMID- 18812552
TI  - Effects of reproductive and demographic changes on breast cancer incidence in
      China: a modeling analysis.
AB  - BACKGROUND: Breast cancer incidence is currently low in China. However, the
      distribution of reproductive and lifestyle risk factors for breast cancer among
      Chinese women is changing rapidly. We quantified the expected effect of changes
      in breast cancer risk factors on future rates of breast cancer in China. METHODS:
      We first validated and calibrated the Rosner-Colditz log-incidence breast cancer
      model in Chinese women who participated in the Shanghai Women's Health Study
      cohort (N = 74,942). We then applied the calibrated model to a representative
      sample of Chinese women who were aged 35-49 years in 2001 using data from the
      Chinese National Family Planning and Reproductive Health Survey (NFPRHS, N =
      17,078) to predict the age-specific and cumulative breast cancer incidence among
      all Chinese women of this age group. We evaluated the relative impact of changes
      in modifiable risk factors, including alcohol intake, parity, postmenopausal
      hormone use, and adult weight gain, on cumulative incidence of breast cancer.
      RESULTS: Breast cancer incidence in China is expected to increase substantially
      from current rates, estimated at 10-60 cases per 100,000 women, to more than 100
      new cases per 100,000 women aged 55-69 years by 2021. We predicted 2.5 million
      cases of breast cancer by 2021 among Chinese women who were 35-49 years old in
      2001. Modest reductions in hormone and alcohol use, and weight maintenance could
      prevent 270,000 of these cases. CONCLUSIONS: China is on the cusp of a breast
      cancer epidemic. Although some risk factors associated with economic development
      are largely unavoidable, the substantial predicted increase in new cases of
      breast cancer calls for urgent incorporation of this disease in future health
      care infrastructure planning.

PMID- 18812554
TI  - Re: Enhancing cancer registry data to promote rational health system design.

PMID- 18812553
TI  - Quantitation of Aurora kinase A gene copy number in urine sediments and bladder
      cancer detection.
AB  - BACKGROUND: Chromosome missegregation and the resulting aneuploidy is a common
      change in neoplasia. The Aurora kinase A (AURKA) gene, which encodes a key
      regulator of mitosis, is frequently amplified and/or overexpressed in cancer
      cells, and the level of AURKA amplification is associated with the level of
      aneuploidy. We examined whether AURKA gene amplification is a biomarker for the
      detection of bladder cancer. METHODS: The effect of ectopic expression of Aurora
      kinase A (AURKA) using an adenoviral vector in simian virus 40-immortalized
      urothelial cells (SV-HUC) on centrosome multiplication and chromosome copy number
      was measured in vitro by immunofluorescence and fluorescence in situ
      hybridization (FISH), respectively. The FISH test was also used to examine AURKA
      gene copy number in exfoliated cells in voided urine samples from 23 patients
      with bladder cancer and 7 healthy control subjects (training set), generating a
      model for bladder cancer detection that was subsequently validated in an
      independent set of voided urine samples from 100 bladder cancer patients and 148
      control subjects (92 healthy individuals and 56 patients with benign urologic
      disorders). An AURKA gene score (the proportion of cells with three or more AURKA
      signals) was used to produce receiver operating characteristic (ROC) curves and
      to calculate the specificity and sensitivity of the AURKA FISH test. Differences
      between mean AURKA scores in different pathogenetic groups of bladder cancer
      stratified according to histological grade and stage were tested by unpaired Mann
      Whitney t tests or one-way Wilcoxon tests. All statistical tests were two-sided.
      RESULTS: Forced overexpression of AURKA in urothelial cells induced amplification
      of centrosomes, chromosome missegregation, and aneuploidy, and natural
      overexpression was detectable in in situ lesions from patients with bladder
      cancer. The FISH test for the AURKA gene copy number performed on the validation
      set yielded a specificity of 96.6% (95% confidence interval [CI] = 92.3% to
      98.5%) and sensitivity of 87% (95% CI = 79.0% to 92.2%) and an area under the ROC
      curve of 0.939 (95% CI = 0.906 to 0.971; P < .001). CONCLUSION: Overexpression of
      AURKA can cause aneuploidy in urothelial cells, and the AURKA gene copy number is
      a promising biomarker for detection of bladder cancer.

PMID- 18812555
TI  - Re: Cost of care for the elderly cancer patients in the United States.

PMID- 18812556
TI  - Re: Endogenous sex hormones and prostate cancer: a collaborative analysis of 18
      prospective studies.

PMID- 18812557
TI  - Pattern approach for diseases of mesenteric small bowel on barium studies.
AB  - Despite an array of sophisticated imaging techniques, the barium examination
      remains a valuable diagnostic test for evaluating structural abnormalities of the
      small bowel. Most patients can be examined with conventional small-bowel follow
      through studies, in which periodic imaging of the entire small bowel is performed
      by using fluoroscopic guidance; however, some patients may benefit from
      enteroclysis, in which contrast agents are instilled into the small bowel via a
      catheter placed in the proximal jejunum for optimal distention and better
      depiction of individual small-bowel loops. This review for residents discusses
      the major diseases involving the mesenteric small bowel and presents a pattern
      approach for the wide spectrum of abnormalities found on barium studies,
      including polypoid lesions, cavitated lesions, annular lesions, outpouchings,
      separation of loops, abnormal folds, nodules without abnormal folds, and dilated
      small bowel.

PMID- 18812558
TI  - Volumetric evaluation of liver metastases after thermal ablation: long-term
      results following MR-guided laser-induced thermotherapy.
AB  - PURPOSE: To volumetrically analyze liver metastases and posttherapeutic findings
      of the thermally ablated area after thermal ablation with magnetic resonance (MR)
      guided laser-induced thermotherapy in a long-term evaluation using contrast
      enhanced MR imaging. MATERIALS AND METHODS: The study was approved by the
      institutional review board, and informed consent was obtained from all patients.
      In 40 patients (27 women, 13 men; age range, 33-94 years; mean age, 62.5 years)
      in whom colorectal cancer (n = 20) and breast cancer (n = 20) had metastasized to
      the liver, initial tumor volume and thermal-induced necrosis after MR-guided
      laser-induced thermotherapy were retrospectively analyzed. All patients presented
      with oligonodular liver metastases and underwent follow-up with contrast-enhanced
      MR imaging for at least 3 years. No concomitant oncologic therapies were
      performed. RESULTS: Volumetric MR imaging evaluation depicted 40 metastases with
      an initial tumor volume less than 5 mL (x = 1.75), nine metastases with initial
      volume of 5-20 mL (x = 12.35), and eight metastases with initial volume more than
      20 mL (x = 50.57). The mean volume of the thermally damaged area was 498% of the
      initial volume for colorectal cancer metastases and 604% of the initial volume
      for breast cancer metastases. The ischemic and necrotic volume for colorectal
      cancer metastases had decreased by a mean of 48.6% after 3 months, by 63% after 6
      months, by 70.2% after 12 months, and by 92.2% after 36 months. For breast cancer
      metastases at 36 months, the necrotic volume had decreased by 80.61%; the
      reduction in the volume of the thermally damaged region was statistically
      significantly lower than that of colorectal cancer metastases. CONCLUSION: MR
      guided laser-induced thermotherapy induced a high volume of thermal ablation; the
      greatest reduction in the necrotic volume occurred in the first year, and lower
      values were seen in the next period. The reduction was statistically
      significantly higher in colorectal cancer metastases.

PMID- 18812559
TI  - Thirty years' experience with balloon dilation of benign postoperative biliary
      strictures: long-term outcomes.
AB  - PURPOSE: To determine the effectiveness of percutaneous balloon dilation of
      benign postoperative biliary strictures. MATERIALS AND METHODS: We received
      approval from our institutional review board to undertake this retrospective
      HIPAA-compliant study, and informed consent was waived. From April 1, 1977, to
      April 1, 2007, percutaneous biliary balloon dilation (PBBD) was performed in 85
      patients with benign biliary strictures. In the 75 patients with follow-up (31
      male, 44 female; mean age, 56 years; mean follow-up, 8 years), 205 PBBD
      procedures were performed during 112 treatments of 84 biliary strictures. PBBD of
      the stricture was performed with a noncompliant balloon (8-12-mm diameter). PBBD
      procedures were repeated at 2- to 14-day intervals until cholangiography
      demonstrated free drainage of contrast material to the bowel and no residual
      stenosis. An internal-external biliary drain was left in situ for a mean of 14-22
      days and removed after a clinical trial of catheter clamping and a normal
      cholangiogram. RESULTS: All procedures were technically successful, and 52, 11,
      10, and two patients underwent a total of one, two, three, and four PBBD
      treatments, respectively. Four of 205 procedures (2%) led to major complications:
      two subphrenic abscesses, one hepatic arterial pseudoaneurysm, and one case of
      hematobilia treated with transfusion. Six patients died from unrelated causes and
      three from hepatitis C-related liver failure. The probability of a patient not
      developing clinically significant restenosis at 5, 10, 15, 20, and 25 years was
      0.52, 0.49, 0.49, 0.41, and 0.41, respectively, after the first PBBD treatment
      and 0.43, 0.30, 0.20, 0.20, and 0.20, respectively, after the second PBBD
      treatment. No significant difference was found in the rate of clinically
      significant restenosis after the first PBBD between strictures at anastomotic and
      nonanastomotic sites (P = .75). During the follow-up period, 56 of 75 patients
      (75%) had successful management with PBBD. CONCLUSION: PBBD of benign strictures
      demonstrates long-term effectiveness. No significant difference was found in the
      rate of clinically significant restenosis after PBBD of biliary strictures at
      anastomotic and nonanastomotic sites.

PMID- 18812560
TI  - Colorectal tumor vascularity: quantitative assessment with multidetector CT--do
      tumor perfusion measurements reflect angiogenesis?
AB  - PURPOSE: To establish the relationships between quantitative perfusion computed
      tomography (CT) parameters-specifically, primary tumor blood flow, blood volume,
      transit time, and permeability surface-area product-and immunohistologic markers
      of angiogenesis in colorectal cancer. MATERIALS AND METHODS: After institutional
      review board approval and informed patient consent were obtained for this
      prospective study, 23 patients (11 men, 12 women; mean age, 68.4 years; age
      range, 34.8-87.1 years) with colorectal adenocarcinoma underwent a 65-second
      perfusion CT examination, and tumor blood flow, blood volume, mean transit time,
      and permeability surface-area product were determined. After surgery, resected
      specimens were sectioned and stained immunohistochemically to identify CD34 for
      quantification of microvessel density (MVD), to identify smooth muscle actin for
      assessment of pericyte coverage index, to identify vascular endothelial growth
      factor (VEGF), and to identify glucose transporter protein (GLUT-1). Perfusion CT
      measurements were correlated with MVD, pericyte coverage index, VEGF expression,
      and GLUT-1 expression by using Pearson or Spearman rank correlation analysis,
      with significance assigned at the 5% level. RESULTS: Mean blood flow, blood
      volume, transit time, and permeability surface-area product values were 72.1
      mL/min/100 g of tissue +/- 28.4 (standard deviation), 6.2 mL/100 g of tissue +/-
      1.4, 9.3 seconds +/- 3.9, and 13.9 mL/min/100 g of tissue +/- 3.2, respectively.
      Blood volume (r = 0.59, P = .002) and permeability surface-area product (r =
      0.46, P = .03) correlated positively with MVD, but blood flow (r = 0.27, P = .22)
      and transit time (r = -0.18, P = .44) did not. There were no significant
      associations between any perfusion CT parameter and pericyte coverage index (r
      <or= 0.36, P > .05), VEGF score (rho <or= 0.30, P >or= .15), or GLUT-1 score (rho
      < 0.21, P >or= .33). CONCLUSION: Tumor permeability surface-area product and
      blood volume correlate positively with MVD and may reflect the microvascularity
      of colorectal tumors.

PMID- 18812561
TI  - Abdominal aorta: evaluation with dual-source dual-energy multidetector CT after
      endovascular repair of aneurysms--initial observations.
AB  - PURPOSE: To evaluate the possible radiation dose reduction facilitated by using
      dual-energy (DE) multidetector computed tomography (CT) after endovascular repair
      of abdominal aortic aneurysms (AAAs). MATERIALS AND METHODS: This prospective
      study was HIPAA compliant and institutional review board approved. Twenty-two
      patients who previously had undergone endovascular repair of AAAs underwent 24 DE
      multidetector CT examinations, which were performed with a 64-detector scanner.
      Initial nonenhanced CT was followed by arterial phase and venous phase
      acquisitions. Virtual nonenhanced, pure 80-kVp, and weighted-average peak voltage
      CT data sets were generated from the venous acquisition. Two independent readers
      interpreted the virtual nonenhanced and DE weighted-average CT data for the
      presence or absence of endoleaks. These interpretations were compared with the
      clinical interpretations of the data performed by a different radiologist by
      using true nonenhanced, arterial phase, and venous phase data. Region-of-interest
      measurements of the abdominal aorta and of the region of the endoleaks were
      obtained. Effective radiation dose was calculated. RESULTS: Both independent
      readers' interpretations of the virtual nonenhanced and weighted-average venous
      CT data revealed six type II endoleaks. There were no false-positive or false
      negative findings. Aortic attenuation during the arterial, 80-kVp venous, and
      weighted-average data acquisitions were 288, 213, and 150 HU, respectively. The
      attenuation of the endoleaks was higher during the 80-kVp acquisition (P < .03)
      than during the arterial phase and weighted-average venous phase acquisitions.
      The mean effective dose for DE venous phase CT was 11.1 mSv compared with 27.8
      mSv for standard triple-phase CT with a single-source configuration. CONCLUSION:
      Preliminary observations suggest that obtaining DE multidetector CT data by using
      a single 60-second contrast material-enhanced acquisition may be all that is
      required for surveillance after endovascular repair of AAA.

PMID- 18812562
TI  - Pharmacokinetic interaction between everolimus and antifungal triazoles in a
      liver transplant patient.
AB  - OBJECTIVE: To describe the management of a pharmacokinetic interaction between
      azole antifungals (fluconazole and voriconazole) and everolimus in a patient who
      underwent an orthotopic liver transplant. CASE SUMMARY: A 65-year-old male who
      received an orthotopic liver transplant experienced an iatrogenic retroperitoneal
      duodenal perforation on postoperative day 55. His condition was subsequently
      complicated by severe sepsis and acute renal failure. Intravenous fluconazole 400
      mg, followed by 100 mg every 24 hours according to impaired renal function, was
      immediately started; to avoid further nephrotoxicity, immunosuppressant therapy
      was switched from cyclosporine plus mycophenolate mofetil to oral everolimus 0.75
      mg every 12 hours. Satisfactory steady-state minimum concentration (C(min)) of
      everolimus was achieved (approximately 5 ng/mL). On day 72 posttransplant,
      because of invasive aspergillosis, antifungal therapy was switched to intravenous
      voriconazole 400 mg every 12 hours on the first day, followed by 200 mg every 12
      hours; to prevent drug toxicity, the everolimus dosage was promptly lowered to
      0.25 mg every 24 hours. At that time, the everolimus C(min) averaged
      approximately 3 ng/mL. The concentration/dose ratio of everolimus (ie, C(min)
      reached at steady-state for each milligram per kilogram of drug administered) was
      markedly lower during fluconazole versus voriconazole cotreatment (mean +/- SD,
      3.49 +/- 0.29 vs 11.05 +/- 0.81 ng/mL per mg/kg/daily; p < 0.001). Despite
      intensive care, the patient's condition continued to deteriorate and he died on
      day 84 posttransplant. DISCUSSION: Both azole antifungals were considered
      probable causative agents of an interaction with everolimus according to the Drug
      Interaction Probability Scale. The interaction is due to the inhibition of CYP3A4
      mediated everolimus clearance. Of note, prompt reduction of the everolimus dosage
      since the first azole coadministration, coupled with intensive therapeutic drug
      monitoring, represented a useful strategy to prevent drug overexposure.
      CONCLUSIONS: Our data suggest that during everolimus-azole cotreatment, a dose
      reduction of everolimus is needed to avoid overexposure. According to the
      different inhibitory potency of CYP3A4 activity, the reduction should be lower
      during fluconazole than during voriconazole cotreatment.

PMID- 18812563
TI  - Severe sepsis caused by Arcanobacterium haemolyticum: a case report and review of
      the literature.
AB  - OBJECTIVE: To describe a case of severe sepsis, cavitary pneumonia, and
      pyomyositis caused by Arcanobacterium haemolyticum. CASE SUMMARY: An 18-year-old
      male with a medical history significant for mild asthma presented to the
      emergency department complaining of a 7-day history of fever, diffuse myalgias,
      nausea, vomiting, diarrhea, and pain in his right upper quadrant, right shoulder,
      and left thigh. Cultures of blood, bronchoalveolar fluid, and surface and
      surgical swabs from the patient's left lower extremity grew A. haemolyticum. The
      patient was successfully treated with intravenous penicillin G 4 million units
      every 4 hours and azithromycin 500 mg once daily for 14 days. Within 36 hours
      after initiation of focused therapy, he became afebrile, pain decreased, and
      pulmonary symptoms abated. Oral azithromycin 500 mg/day for an additional 3 weeks
      was prescribed on discharge, and the patient showed no relapse at 2-month follow
      up. DISCUSSION: A. haemolyticum is a weakly acid-fast, branching gram-positive
      bacillus most commonly implicated in pharyngitis in healthy adolescents and skin
      and soft-tissue infections in older, immunocompromised patients. Systemic
      infections are rarely reported in the literature. This organism remains
      susceptible to most classes of antimicrobials, including penicillins,
      cephalosporins, carbapenems, macrolides, tetracyclines, clindamycin, and
      vancomycin. Routine resistance has been reported only with
      trimethoprim/sulfamethoxazole. CONCLUSIONS: To our knowledge, there are no
      published case reports of severe sepsis caused by A. haemolyticum. While
      treatment options are numerous, we recommend the use of intravenous penicillin or
      a cephalosporin as first-line pharmacologic management of deep-seated infections
      caused by this rare organism.

PMID- 18812565
TI  - Caspase-2: vestigial remnant or master regulator?
AB  - Caspase-2, the second mammalian caspase to be identified and the most
      evolutionarily conserved caspase, has eluded classification. The lack of a
      profound phenotype in the caspase-2-deficient mouse resulted in decreased
      interest in caspase-2 for many years. However, advances in the field, including
      the identification of a potential activation complex and the development of
      methods to detect active caspase-2, now illuminate our understanding of the
      function of this caspase. These studies suggest that caspase-2 induces death
      through two pathways. First, caspase-2 induces cell death independently of the
      mitochondrial pathway, in a manner similar to that of ced-3, a caspase in
      Caenorhabditis elegans. Second, caspase-2 also induces cell death upstream of the
      mitochondrial pathway. The choice of pathway may depend on the type of death
      stimulus. The placing of caspase-2 upstream and independent of mitochondrial
      dysfunction provides a potentially new therapeutic target for aberrant cell
      death.

PMID- 18812566
TI  - Nedd4 controls animal growth by regulating IGF-1 signaling.
AB  - The ubiquitin ligase Nedd4 has been proposed to regulate a number of signaling
      pathways, but its physiological role in mammals has not been characterized. Here
      we present an analysis of Nedd4-null mice to show that loss of Nedd4 results in
      reduced insulin-like growth factor 1 (IGF-1) and insulin signaling, delayed
      embryonic development, reduced growth and body weight, and neonatal lethality. In
      mouse embryonic fibroblasts, mitogenic activity was reduced, the abundance of the
      adaptor protein Grb10 was increased, and the IGF-1 receptor, which is normally
      present on the plasma membrane, was mislocalized. However, surface expression of
      IGF-1 receptor was restored in homozygous mutant mouse embryonic fibroblasts
      after knockdown of Grb10, and Nedd4(-/-) lethality was rescued by maternal
      inheritance of a disrupted Grb10 allele. Thus, in vivo, Nedd4 appears to
      positively control IGF-1 and insulin signaling partly through the regulation of
      Grb10 function.

PMID- 18812567
TI  - High-throughput analysis of HGF-stimulated cell scattering.
AB  - Historically, only relatively low-throughput or expensive methods have been
      available to measure cell migration. Hepatocyte growth factor (HGF) is a ligand
      for the tyrosine kinase receptor Met that, in addition to mediating proliferation
      and survival, increases cell motility and metastasis. The authors have developed
      a high-throughput imaging assay for measuring inhibition of HGF-induced
      scattering in human HPAF-II pancreatic adenocarcinoma cells. Following treatment
      with test compounds and HGF for 24 h, cells are labeled with a nuclear stain and
      imaged at 10x magnification. The proximity of neighboring nuclei is measured, and
      the distribution of internuclear distances across each field of view is used to
      calculate the fraction of scattered cells. This method of analysis can be
      extended to other cell types and signaling pathways and, compared with other
      membrane-based migration assays currently available, the assay is significantly
      lower in cost, is less labor intensive, and provides higher throughput.

PMID- 18812568
TI  - Identification of small molecule inhibitors of beta-amyloid cytotoxicity through
      a cell-based high-throughput screening platform.
AB  - Calpain activation is hypothesized to be an early occurrence in the sequence of
      events resulting in neurodegeneration, as well as in the signaling pathways
      linking extracellular accumulation of beta-amyloid (Abeta) peptides and
      intracellular formation of neurofibrillary tangles. In an effort to identify
      small molecules that prevent neurodegeneration in Alzheimer's disease by early
      intervention in the cell death cascade, a cell-based assay in differentiated Sh
      SY5Y cells was developed using calpain activity as a read-out for the early
      stages of death in cells exposed to extracellular Abeta. This assay was optimized
      for high-throughput screening, and a library of approximately 120,000 compounds
      was tested. It was expected that the compounds identified as calpain inhibitors
      would include those that act directly on the enzyme and those that prevented
      calpain activation by blocking an upstream step in the pathway. In fact, of the
      compounds that inhibited calpain activation by Abeta with IC(50) values of <10
      microM and showed little or no toxicity at concentrations up to 30 microM, none
      inhibit the calpain enzyme directly.

PMID- 18812569
TI  - Genome-wide oligonucleotide microarray analysis of gene-expression profiles of
      Taiwanese patients with anaplastic astrocytoma and glioblastoma multiforme.
AB  - This study investigated the relationship between gene expression and disease
      based on the expression profiles of tissue-specific genes, with the aim of
      discovering the candidate genes associated with disease risk as diagnostic
      markers. The gene-expression profiles of approximately 20,000 genes from 4
      anaplastic astrocytomas (AAs), 7 glioblastoma multiformes (GBMs), and 1 nontumor
      brain (NB) were analyzed by in situ-synthesized 60-mer oligonucleotide
      microarray. The signal intensity of each feature was measured by laser scanner,
      and gene expression was quantified as the tumor/NB intensity ratio. Gene
      expression was defined as having increased or decreased when the ratio was
      >or=1.5 or <or= 0.67, respectively. In comparison with NB, 20 genes showed
      increased expression, and 32 showed decreased expression in AA, while 20 genes
      showed increased expression, and 164 showed decreased expression in GBM. This
      research indicates that changes in expression levels of 4 genes in AA and 6 genes
      in GBM may be useful diagnostic markers. Quantitative reverse transcription
      polymerase chain reaction also supported the microarray results for the 6
      selected genes. In conclusion, microarray images of excellent quality are of high
      data reproducibility using entirely standard procedures, and these genes may be
      associated with the molecular events leading to AA or GBM.

PMID- 18812570
TI  - A high-throughput liposome substrate assay with automated lipid extraction
      process for PI 3-kinase.
AB  - The signaling pathways involving lipid kinase class I phosphatidylinositol 3
      kinases (PI 3-kinases) regulate cell growth, proliferation, and survival. Class I
      PI 3-kinases catalyze the conversion of PI (4,5)P(2) to PI (3,4,5)P(3), which
      acts as a lipid second messenger to activate mitogenic signaling cascades.
      Recently, p110alpha, a class IA PI 3-kinase, was found to be mutated frequently
      in many human cancers. Therefore, it is increasingly studied as an anticancer
      drug target. Traditionally, PI 3-kinase activities have been studied using
      liposome substrates. This method, however, is hampered significantly by the labor
      intensive manual lipid extraction followed by a low-throughput thin-layer
      chromatography analysis. The authors describe a high-throughput liposome
      substrate-based assay based on an automated lipid extraction method that allows
      them to study PI 3-kinase enzyme mechanism and quantitatively measure inhibitor
      activity using liposome substrates in a high-throughput mode. This improved assay
      format can easily be extended to study other classes of phosphoinositide lipid
      kinases.

PMID- 18812571
TI  - High-throughput screening of a 100,000-compound library for inhibitors of
      influenza A virus (H3N2).
AB  - Using a highly reproducible and robust cell-based high-throughput screening (HTS)
      assay, the authors screened a 100,000-compound library at 14- and 114-microM
      compound concentration against influenza strain A/Udorn/72 (H3N2). The "hit"
      rates (>50% inhibition of the viral cytopathic effect) from the 14- and 114
      microM screens were 0.022% and 0.38%, respectively. The hits were evaluated for
      their antiviral activity, cell toxicity, and selectivity in dose-response
      experiments. The screen at the lower concentration yielded 3 compounds, which
      displayed moderate activity (SI(50) = 10-49). Intriguingly, the screen at the
      higher concentration revealed several additional hits. Two of these hits were
      highly active with an SI(50) > 50. Time of addition experiments revealed 1
      compound that inhibited early and 4 other compounds that inhibited late in the
      virus life cycle, suggesting they affect entry and replication, respectively. The
      active compounds represent several different classes of molecules such as
      carboxanilides, 1-benzoyl-3-arylthioureas, sulfonamides, and benzothiazinones,
      which have not been previously identified as having antiviral/anti-influenza
      activity.

PMID- 18812572
TI  - The application of an immobilized molecular beacon for the analysis of the DNA
      binding domains from the ecdysteroid receptor proteins Usp and EcR's interaction
      with the hsp27 response element.
AB  - The nonstandard molecular beacon described in this article consists of 2
      fragments, each built of a short single-stranded oligonucleotide sequence and a
      double-stranded sequence. One of these hybridization probes, labeled with a
      fluorescence donor (fluorescein), is solid phase immobilized. The second
      nonimmobilized probe is labeled with a fluorescence quencher (dabcyl). Annealing
      of both probes via single-stranded sequences was possible only in the presence of
      a specific protein molecule that recognized the response element sequence
      initially separated between the immobilized and nonimmobilized fragments. The
      system was applied successfully to detect the sequence-specific interaction of a
      natural hsp27 response element from the promoter of the hsp27 gene with the DNA
      binding domains of 2 nuclear receptor proteins: ultraspiracle Usp (UspDBD) and
      the ecdysone receptor EcR (EcRDBD). Measured in the absence of EcRDBD, the
      dissociation constant, K(d) of the UspDBD-hsp27 complex, was determined to be
      3.26 nM, whereas for UspDBD devoid of the A-box (UspDBDDeltaA-hsp27 ), the
      dissociation constant was 4.81 nM. The respective K(d) values in the presence of
      EcRDBD were 2.43 nM and 10.80 nM. The results obtained with the immobilized
      molecular beacon technology were in agreement with those obtained by conventional
      fluorescence titrations and by fluorescence resonance energy transfer
      measurements with nonimmobilized beacons.

PMID- 18812573
TI  - High-throughput microsomal stability assay for screening new chemical entities in
      drug discovery.
AB  - In this work, the authors present a novel, robotic, automated protocol for
      assessing a metabolic stability protocol assembled on a Hamilton platform and a
      new strategy for pooling samples (cassette analysis). To increase the high
      throughput of the liquid chromatography (LC) step, fast chromatography and
      automated liquid chromatography tandem mass spectrometry (LC/MS/MS) analytical
      methods were also developed, and a rapid data analysis system was generated that
      converts peak areas obtained by LC/MS/MS in intrinsic clearance values. All of
      the steps of the microsomal stability assay were carefully studied and optimized.
      Standard errors and confidence intervals of the measured clearances were also
      automatically generated in the process to allow an immediate evaluation of the
      significance of observed values. Methods based on pooling analysis of 2 and 4
      different analytes were compared with a standard method without pooling. A simple
      statistical treatment was used to show their equivalence. The different protocols
      developed were analyzed in terms of the best compromise between accuracy and high
      throughput capabilities.

PMID- 18812574
TI  - Demonstration of improvements to the bioluminescence resonance energy transfer
      (BRET) technology for the monitoring of G protein-coupled receptors in live
      cells.
AB  - The bioluminescence resonance energy transfer (BRET) technique has become
      extremely popular for studying protein-protein interactions in living cells and
      real time. Of particular interest is the ability to monitor interactions between
      G protein-coupled receptors, such as the thyrotropin-releasing hormone receptor
      (TRHR), and proteins critical for regulating their function, such as beta
      arrestin. Using TRHR/beta-arrestin interactions, we have demonstrated
      improvements to all 3 generations of BRET (BRET(1), BRET(2), and eBRET) by using
      the novel forms of luciferase, Rluc2 and Rluc8, developed by the Gambhir
      laboratory. Furthermore, for the 1st time it was possible to use the BRET2 system
      to detect ligand-induced G protein-coupled receptor/beta-arrestin interactions
      over prolonged periods (on the scale of hours rather than seconds) with a very
      stable signal. As demonstrated by our Z'-factor data, these luciferases increase
      the sensitivity of BRET to such an extent that they substantially increase the
      potential applicability of this technology for effective drug discovery high
      throughput screening.

PMID- 18812575
TI  - Activation and translocation of glucokinase in rat primary hepatocytes monitored
      by high content image analysis.
AB  - In the liver, glucokinase (GK) regulatory protein (GKRP) negatively modulates the
      metabolic enzyme GK by locking it in an inactive state in the nucleus. Here, the
      authors established a high content screening assay in the 384-well microplate
      format to measure the nucleus-to-cytoplasm translocation of GK by reagents that
      destabilize the interaction between GK and GKRP. As a cellular model system,
      primary rat hepatocytes endogenously expressing both GK and GKRP at physiological
      levels were used. The GK translocation assay was robust, displayed limited day-to
      day variability, and delivered good Z' statistics. The increase of the glucose
      concentration in the extracellular medium from a low glucose situation (2.8 mM)
      to beyond its physiological set point value of 5 mM was found to drive GK from
      the nucleus into the cytoplasm. Likewise, both fructose (converted
      intracellularly into fructose-1-phosphate) and a known allosteric GK activator
      were found to induce the export of GK from the nucleus and to synergistically
      enhance the effects of medium or high glucose concentrations with respect to GK
      translocation. Transfer of the high content screening format to a semiautomated
      medium throughput screening platform enabled the profiling of large compound
      numbers with respect to allosteric activation of GK.

PMID- 18812576
TI  - A novel high-throughput screening assay for putative antidiabetic agents through
      PPARalpha interactions.
AB  - As natural peroxisome proliferator-activated receptor-alpha (PPARalpha) ligands,
      high levels of fatty acids and glucose could lead to hyperactivation of
      PPARalpha, like that seen in diabetes. Important diabetes research goals are to
      uncover new metabolic or signaling pathways involved in hyperglycemic cellular
      injury and to develop therapeutics for preventing or reversing this injury.
      Consequently, 1040 putative antidiabetic agents were screened for their ability
      to 1) affect PPARalpha lipid binding, 2) directly bind PPARalpha, and 3) alter
      PPARalpha transactivation in the presence of high glucose. A high-throughput
      fluorescent binding assay was developed to examine each compound's ability to
      restore fatty acyl-CoA binding to PPARalpha in the presence of high glucose
      concentrations. Approximately 1% of the compounds restored acyl-CoA binding by
      60% or more. These compounds directly interacted with PPARalpha with high
      affinity (nM K(d)s), validating the primary screen. Furthermore, these compounds
      altered PPARalpha transactivation, and 1 strongly reversed the hyperactivation of
      PPARalpha found in the presence of clofibrate and high glucose levels.

PMID- 18812577
TI  - Influence of Helicobacter hepaticus infection on the chronic toxicity and
      carcinogenicity of triethanolamine in B6C3F1 mice.
AB  - Helicobacter hepaticus (H. hepaticus) infection causes hepatitis and increased
      hepatocellular neoplasms in male mice; although females are also infected, liver
      lesions are not typically expressed. In the 1990s, B6C3F1 mice from some chronic
      National Toxicology Program (NTP) studies were found to be infected with H.
      hepaticus. In these studies, there was hepatitis in many of the males, and there
      were more hepatocellular neoplasms in control males compared to studies with
      uninfected mice. In one of these studies, increased hepatocellular neoplasms at
      the high doses in male and female mice exposed topically to triethanolamine (TEA)
      provided the only evidence of carcinogenic activity. This study was repeated in
      mice free of H. hepaticus.However, the NTP mouse production colony and the diet
      differed between studies; these differences were the result of NTP programmatic
      decisions. In repeat study males, although control incidences were similar
      between studies, exposure did not result in increased hepatocellular neoplasms.
      In repeat study females, the control incidence of hepatocellular neoplasms was
      half that observed in the initial study, and these neoplasms were increased over
      controls at all doses. These data suggest that in the initial study, H.
      hepaticusinfluenced the induction of hepatocellular neoplasms in males, but not
      in females.

PMID- 18812580
TI  - Arsenic-induced decreases in the vascular matrix.
AB  - Chronic ingestion of arsenic is associated with increased incidence of
      respiratory and cardiovascular diseases. To investigate the role of arsenic in
      early events in vascular pathology, C57BL/6 mice ingested drinking water with or
      without 50 ppb sodium arsenite (AsIII) for four, five, or eight weeks. At five
      and eight weeks, RNA from the lungs of control and AsIII-exposed animals was
      processed for microarray. Sixty-five genes were significantly and differentially
      expressed. Differential expression of extracellular matrix (ECM) gene transcripts
      was particularly compelling, as 91% of genes in this category, including elastin
      and collagen, were significantly decreased. In additional experiments, real-time
      RT-PCR showed an AsIII-induced decrease in many of these ECM gene transcripts in
      the heart and NIH3T3 fibroblast cells. Histological stains for collagen and
      elastin show a distinct disruption in the ECM surrounding small arteries in the
      heart and lung of AsIII-exposed mice. Immunohistochemical detection of alpha
      smooth muscle actin in blood vessel walls was decreased in the AsIII-exposed
      animals. These data reveal a functional link between AsIII exposure and
      disruption in the vascular ECM. These AsIII-induced early pathological events may
      predispose humans to respiratory and cardiovascular diseases linked to chronic
      low-dose AsIII exposure.

PMID- 18812581
TI  - The effect of fasting on hepatic lipid accumulation and transcriptional
      regulation of lipid metabolism differs between C57BL/6J and BALB/cA mice fed a
      high-fat diet.
AB  - The effects of fasting on hepatic lipid metabolism in mice fed a high-fat diet
      (HFD) are still unclear. After fasting, the degree of hepatic lipid accumulation
      differs between HFD-fed C57BL/6J (B6) and BALB/cA (BALB/c) mice. It is not clear
      whether this difference is due to sensitivity to fasting or HFD. The aim of this
      study is to elucidate this difference among strains. After nine weeks of HFD
      feeding, both B6 and BALB/c mice showed moderate hepatic steatosis. However,
      after a subsequent twenty-hour fast, the hepatic lipid accumulation was markedly
      decreased in B6 but not in BALB/c mice. Moreover, the mRNA expression of a
      transcription factor, Srebp1(regulates hepatic lipid metabolism), and its target
      genes-malic enzyme, acetyl-CoA carboxylase, fatty acid synthase(regulate fatty
      acid synthesis), and glycerol-3-phosphate acyltransferase(regulates
      triacylglycerol synthesis)-were more markedly reduced in B6 than BALB/c mice. In
      conclusion, fasting may modify hepatic lipid accumulation in HFD-fed B6 and
      BALB/c mice differently. The difference may be partly owing to a marked
      downregulation of the expression of some lipid-metabolism-related genes in B6
      mice. These results suggest that fasting per se has a significant effect on
      hepatic lipid accumulation in mouse strains. SREBP1 might play a role in this
      fasting effect.

PMID- 18812582
TI  - A multiattribute model for evaluating the benefit-risk profiles of treatment
      alternatives.
AB  - The assessment of the benefits and risks associated with a medicine's use
      requires careful consideration of a wealth of information of varying format and
      quality, ranging from efficacy and safety data derived from randomized clinical
      trials to statistical results from health outcomes studies to spontaneously
      reported adverse events. Contrary to the expectations of patients, physicians,
      and regulators, the literature offers little guidance as to how to strike an
      appropriate balance between benefit and risk. Although a qualitative listing of a
      medicine's benefits and risks is useful, much could be gained from a systematic
      and transparent process to evaluate a medicine's pre- and postmarketing
      performance. The authors propose a representational model based on multicriteria
      decision analysis that can incorporate both evaluative judgments from different
      perspectives (e.g., physician, patient) and quantitative data to inform tradeoffs
      between multiple benefit and multiple risk elements in a logically consistent and
      transparent manner. The model is designed to highlight the relative merits and
      deficits of treatment alternatives in well-defined and specific contexts. It is
      intended to serve as a common platform to facilitate focused benefit-risk
      tradeoff discussions between scientists, physicians, regulatory authorities, and
      pharmaceutical companies, and to assist in the communication of clear and
      consistent messages regarding those tradeoffs.

PMID- 18812583
TI  - Incorporating uncertainty into medical decision making: an approach to unexpected
      test results.
AB  - The utility of diagnostic tests derives from the ability to translate the
      population concepts of sensitivity and specificity into information that will be
      useful for the individual patient: the predictive value of the result. As the
      array of available diagnostic testing broadens, there is a temptation to de
      emphasize history and physical findings and defer to the objective rigor of
      technology. However, diagnostic test interpretation is not always
      straightforward. One significant barrier to routine use of probability-based test
      interpretation is the uncertainty inherent in pretest probability estimation, the
      critical first step of Bayesian reasoning. The context in which this uncertainty
      presents the greatest challenge is when test results oppose clinical judgment. It
      is this situation when decision support would be most helpful. The authors
      propose a simple graphical approach that incorporates uncertainty in pretest
      probability and has specific application to the interpretation of unexpected
      results. This method quantitatively demonstrates how uncertainty in disease
      probability may be amplified when test results are unexpected (opposing clinical
      judgment), even for tests with high sensitivity and specificity. The authors
      provide a simple nomogram for determining whether an unexpected test result
      suggests that one should "switch diagnostic sides.'' This graphical framework
      overcomes the limitation of pretest probability uncertainty in Bayesian analysis
      and guides decision making when it is most challenging: interpretation of
      unexpected test results.

PMID- 18812584
TI  - Lessons learned by (from?) an economist working in medical decision making.
AB  - This article is a personal account of the author's experiences as an economist
      working in medical decision making. He discusses the differences between economic
      decision theory and medical decision making and gives examples of the mutual
      benefits resulting from interactions. In particular, he discusses the pros and
      cons of different methods for measuring quality of life (or, as economists would
      call it, utility), including the standard gamble, the time tradeoff, and the
      healthy-years equivalent methods.

PMID- 18812585
TI  - Modifying ICD-9-CM coding of secondary diagnoses to improve risk-adjustment of
      inpatient mortality rates.
AB  - OBJECTIVE: To assess the effect on risk-adjustment of inpatient mortality rates
      of progressively enhancing administrative claims data with clinical data that are
      increasingly expensive to obtain. Data Sources. Claims and abstracted clinical
      data on patients hospitalized for 5 medical conditions and 3 surgical procedures
      at 188 Pennsylvania hospitals from July 2000 through June 2003. METHODS: Risk
      adjustment models for inpatient mortality were derived using claims data with
      secondary diagnoses limited to conditions unlikely to be hospital-acquired
      complications. Models were enhanced with one or more of 1) secondary diagnoses
      inferred from clinical data to have been present-on-admission (POA), 2) secondary
      diagnoses not coded on claims but documented in medical records as POA, 3)
      numerical laboratory results from the first hospital day, and 4) all available
      clinical data from the first hospital day. Alternative models were compared using
      c-statistics, the magnitude of errors in prediction for individual cases, and the
      percentage of hospitals with aggregate errors in prediction exceeding specified
      thresholds. RESULTS: More complete coding of a few under-reported secondary
      diagnoses and adding numerical laboratory results to claims data substantially
      improved predictions of inpatient mortality. Little improvement resulted from
      increasing the maximum number of available secondary diagnoses or adding
      additional clinical data. CONCLUSIONS: Increasing the completeness and
      consistency of reporting a few secondary diagnosis codes for findings POA and
      merging claims data with numerical laboratory values improved risk adjustment of
      inpatient mortality rates. Expensive abstraction of additional clinical
      information from medical records resulted in little further improvement.

PMID- 18812586
TI  - Computer and internet use in a community health clinic population.
AB  - OBJECTIVE: To determine if patients from a community health clinic have access to
      computers and/or the Internet and if they believe a computer is useful in their
      medical care. METHODS: A convenience sample of 100 subjects, aged 50 years and
      older, from a community health clinic in Nashville, Tennessee, completed a
      structured interview and a health literacy assessment. RESULTS: Of the 100
      participants, 40 did not have any computer access, 27 had computer but not
      Internet access, and 33 had Internet access. Participants with computer access
      (with or without Internet) had higher incomes, higher educational status, and
      higher literacy status than those without computer access. Of participants
      reporting current computer use (n = 54), 33% reported never using their computer
      to look up health and medical information. Of those who "never'' used their
      computer for this activity, 54% reported they did not have Internet connectivity,
      whereas 31% reported they did not know how to use the Internet. Although this
      group of individuals reported that they were comfortable using a computer (77%),
      they reported being uncomfortable with accessing the Internet (53%). CONCLUSIONS:
      Not only does access to computers and the Internet need to be improved before
      widespread use by patients, but computer users will need to be instructed on how
      to navigate the Internet.

PMID- 18812587
TI  - School experiences of families of children with brain tumors.
AB  - Families and children often report a diverse range of academic achievements and
      challenges after undergoing treatment for a brain tumor. This study explores the
      experiences of children, youth, and their families as they seek to reintegrate
      into mainstream educational systems. Despite the variable experiences, there are
      many common strategies that could positively influence the child's success in
      school. Strong communication between parents, school, and health professionals is
      paramount. Preparing parents to advocate for their children's academic and social
      needs and developing an awareness of the challenges among school staff has
      potential to improve outcomes for these children. Equipping the children with the
      social skills needed to manage social situations will strengthen their ability to
      overcome the challenges that they face. These study findings shed light on the
      academic experiences of these children and can lead to the development of
      strategies to support families facing similar challenges.

PMID- 18812588
TI  - Fertility issues of childhood cancer survivors: the role of the pediatric nurse
      practitioner in fertility preservation.
AB  - The purpose of this review is to discuss the role of the pediatric nurse
      practitioner (PNP) surrounding the survivorship issue of infertility. The author
      outlines the effects of treatment, examines available options, explores ethical
      and legal issues, discusses the role of the PNP, and addresses areas of further
      research. The issue of postcancer reproductive health is increasing in importance
      as both the number of cancer survivors and length of survival increases.
      Approximately 1 out of every 900 individuals in the United States between the
      ages of 15 and 45 years is a survivor of childhood cancer. In fact, the survival
      rates for childhood cancer have improved dramatically. Sexual function and
      fertility in children and adolescents has become a prominent issue, and this
      review illustrates the gap between care providers and patients and describes how
      PNPs must fill this gap to manage the adverse effects on fertility and gonadal
      dysfunction.

PMID- 18812589
TI  - The pediatric cancer hospitalization experience: reality co-constructed.
AB  - Although pediatric cancer treatment has been reviewed by several authors, the
      lived experiences of children undergoing this process have seldom been discussed
      in the literature. The data for this article were obtained from a larger
      qualitative study that provided a collective view of the pediatric cancer
      experience at San Jorge Children's Hospital in Puerto Rico. In this article,
      findings that are directly related to the hospitalization process of these young
      patients are described, including the hospital as a safe haven, dealing with
      pain, taking control, and thriving in adversity. These findings provide a
      rationale for the development of a biopsychosocial model of health that
      emphasizes reciprocal interactions among the biological, psychological, social,
      cultural, and spiritual dimensions that influence health.

PMID- 18812590
TI  - Nonadherence increases the risk of hospitalization among HIV-infected
      antiretroviral naive patients started on HAART.
AB  - BACKGROUND: Since the advent of highly active antiretroviral therapy (HAART),
      AIDS-related hospitalizations have decreased. The objective of this study was to
      assess the impact of adherence on hospitalization among antiretroviral-naive HIV
      infected persons initiating HAART. METHODS: Analysis was based on a cohort of
      individuals initiating HAART between 1996 and 2001. The primary outcome was
      hospitalization for one or more days. Survival methods were used to assess the
      impact of adherence on hospitalization. RESULTS: Of 1605 eligible participants,
      672 (42%) were hospitalized for one or more days after initiating HAART. Median
      adherence levels were 92 (IQR: 58, 100) and 100 (IQR: 83, 100) among those ever
      and never hospitalized, respectively. After controlling for confounders, those
      with <95% adherence had 1.88 times (95% CI: 1.60, 2.21) higher risk for
      hospitalization. CONCLUSIONS: Suboptimal adherence among HIV-infected patients
      taking HAART predicts hospitalization. Identifying and addressing factors
      contributing to poor adherence early in treatment could improve patient care and
      lower hospitalization costs.

PMID- 18812591
TI  - Hyper interleukin-10 in an HIV-positive child with t-cell lymphoma and candidal
      sepsis.
AB  - We describe a case in which a human immunodeficiency virus (HIV)-positive child
      presented in severe metabolic acidosis secondary to his candidal sepsis and T
      cell lymphoma, a rare finding in pediatric AIDS. Significantly elevated levels of
      Interleukin-10 (IL-10) were found in the patient's serum, which may have played a
      role in acute demise.

PMID- 18812592
TI  - Challenges of diagnosis and management of tuberculosis and HIV coinfection in
      resource-limited settings: a case report from Lima, Peru.
AB  - We present a Peruvian human immunodeficiency virus (HIV)-positive patient
      receiving first-line therapy for tuberculosis who presents with neurological
      complications to highlight some of the major issues in the diagnosis and
      management of human immunodeficiency virus-related central nervous system
      complications in resource-poor settings. These include limited options for
      diagnosing extrapulmonary and drug-resistant tuberculosis; the importance of
      central nervous system . imaging; and the management conundrum when faced with a
      broad differential diagnosis. This patient was with drug-resistant tuberculosis
      of the brain, unmasked by immunologic recovery in the setting of recent
      initiation of antiretroviral treatment. We argue that aggressive and timely
      empiric multidrug-resistant tuberculosis treatment is important in cases where
      drug-resistant tuberculosis is suspected. Knowledge gaps include a limited
      understanding of immune reconstitution and the optimal timing of antiretroviral
      treatment in the setting of drug-resistant tuberculosis.

PMID- 18812593
TI  - Effect of postpartum HIV treatment discontinuation on long-term maternal outcome.
AB  - BACKGROUND: Long-term maternal outcomes after postpartum antiretroviral therapy
      (ART) discontinuation are unknown. METHODS: Retrospective review of pregnancies
      in HIV-infected women on treatment between 1997 and 2005. Women were grouped by
      postpartum ART use and followed until new opportunistic infection (OI), death or
      last clinic visit. RESULTS: Of 172 pregnancies, postpartum ART discontinuation
      occurred in 123 (71.5%) women and was associated with greater parity, no partner
      during pregnancy, and no indication for OI prophylaxis or preconception ART in
      multivariate analysis (P < .05). Median follow-up was 32.5 months after delivery.
      There were 12 OIs and 2 deaths; 10 OIs and both deaths occurred in women who had
      discontinued ART. CONCLUSION: Postpartum ART discontinuation is common,
      especially among those with less advanced HIV disease, but may leave women at
      increased risk of long term adverse outcomes. This study highlights the need for
      larger longitudinal studies to determine appropriate recommendations for
      postpartum ART administration.

PMID- 18812594
TI  - A case report of recurrent Salmonella meningitis in an adult AIDS patient in the
      United States.
AB  - The authors present a case of Salmonella sepsis and meningitis with a recurrence
      of the meningitis in a 36-year-old Hispanic, male AIDS patient. They discuss the
      mechanisms and routes in general and speculate on these items in this patient
      from the information available. Meningitis diagnosis and treatment in general and
      specifically in Salmonella cases are reviewed as well as the variations in AIDS
      patients. The probable reasons for the recurrence and etiology are discussed.

PMID- 18812595
TI  - Synthetic LXR agonist attenuates plaque formation in apoE-/- mice without
      inducing liver steatosis and hypertriglyceridemia.
AB  - Liver X receptors (LXRs) are important regulators of cholesterol and lipid
      metabolism. LXR agonists have been shown to limit the cellular cholesterol
      content by inducing reverse cholesterol transport, increasing bile acid
      production, and inhibiting intestinal cholesterol absorption. Most of them,
      however, also increase lipogenesis via sterol regulatory element-binding protein
      1c (SREBP1c) and carbohydrate response element-binding protein activation
      resulting in hypertriglyceridemia and liver steatosis. We report on the
      antiatherogenic properties of the steroidal liver X receptor agonist N,N-dimethyl
      3beta-hydroxy-cholenamide (DMHCA) in apolipoprotein E (apoE)-deficient mice. Long
      term administration of DMHCA (11 weeks) significantly reduced lesion formation in
      male and female apoE-null mice. Notably, DMHCA neither increased hepatic
      triglyceride (TG) levels in male nor female apoE-deficient mice. ATP binding
      cassette transporter A1 and G1 and cholesterol 7alpha-hydroxylase mRNA abundances
      were increased, whereas SREBP1c mRNA expression was unchanged in liver, and even
      decreased in macrophages and intestine. Short-term treatment revealed even higher
      changes on mRNA regulation. Our data provide evidence that DMHCA is a strong
      candidate as therapeutic agent for the treatment or prevention of
      atherosclerosis, circumventing the negative side effects of other LXR agonists.

PMID- 18812597
TI  - Study of the scan uniformity from an i-CAT cone beam computed tomography dental
      imaging system.
AB  - OBJECTIVES: As part of an ongoing programme to improve diagnosis and treatment
      planning relevant to implant placement, orthodontic treatment and
      dentomaxillofacial surgery, a study has been made of the spatial accuracy and
      density response of an i-CAT, a cone beam CT (CBCT) dental imaging system
      supplied by Imaging Sciences International Inc. METHODS: Custom-made phantoms
      using acrylic sheet and water were used for measurements on spatial accuracy,
      density response and noise. The measurements were made over a period of several
      months on a clinical machine rather than on a machine dedicated to research.
      RESULTS: Measurements on a precision grid showed the spatial accuracy to be
      universally within the tolerance of +/-1 pixel. The density response and the
      noise in the data were found to depend strongly on the mass in the slice being
      scanned. CONCLUSIONS: The density response was subject to two effects. The first
      effect changes the whole slice uniformly and linearly depends on the total mass
      in the slice. The second effect exists when there is mass outside the field of
      view, dubbed the "exo-mass" effect. This effect lowers the measured CT number
      rapidly at the scan edge furthest from the exo-mass and raises it on the adjacent
      edge. The noise also depended quasi-linearly on the mass in the slice. Some
      general performance rules were drafted to describe these effects and a
      preliminary correction algorithm was constructed.

PMID- 18812596
TI  - Triglyceride-rich lipoprotein lipolysis releases neutral and oxidized FFAs that
      induce endothelial cell inflammation.
AB  - Triglyceride-rich lipoprotein (TGRL) lipolysis products provide a pro
      inflammatory stimulus that can alter endothelial barrier function. To probe the
      mechanism of this lipolysis-induced event, we evaluated the pro-inflammatory
      potential of lipid classes derived from human postprandial TGRL by lipoprotein
      lipase (LpL). Incubation of TGRL with LpL for 30 min increased the saturated and
      unsaturated FFA content of the incubation solutions significantly. Furthermore,
      concentrations of the hydroxylated linoleates 9-hydroxy ocatadecadienoic acid (9
      HODE) and 13-HODE were elevated by LpL lipolysis, more than other measured
      oxylipids. The FFA fractions elicited pro-inflammatory responses inducing
      TNFalpha and intracellular adhesion molecule expression and reactive oxygen
      species (ROS) production in human aortic endothelial cells (HAECs). The FFA
      mediated increase in ROS was blocked by both the cytochrome P450 2C9 inhibitor
      sulfaphenazole and NADPH oxidase inhibitors. Compared with linoleate, 13-HODE was
      found to be a more potent inducer of ROS production in HAECs, an activity that
      was insensitive to both NADPH oxidase and cytochrome P450 inhibitors. Therefore,
      although the oxidative metabolism of FFA in endothelial cells can produce
      inflammatory responses, TGRL lipolysis can also release preformed mediators of
      oxidative stress (e.g., HODEs) that may influence endothelial cell function in
      vivo by stimulating intracellular ROS production.

PMID- 18812598
TI  - Selecting regions of interest on intraoral radiographs for the prediction of bone
      mineral density.
AB  - OBJECTIVES: A previous study showed that the trabecular pattern on dental
      radiographs correlates with femoral and spinal bone mineral density (BMD). The
      objective of this study was to determine if the correlation is affected by the
      size and location of the region of interest (ROI). METHODS: In a European
      research project on osteoporosis, BMD was measured at the left hip and the lumbar
      spine of 525 women. From all subjects, intraoral radiographs were made of the
      premolar region in the upper and lower jaws. Two ROIs were indicated manually on
      each scanned image. The smallest region involved only trabecular bone and the
      largest also included parts of the neighbouring teeth. The ROIs were subjected to
      automatic image analysis, yielding 26 measurements per ROI. Stepwise linear
      regression was used to predict femoral and spinal BMD. RESULTS: Inner and outer
      regions predicted BMD equally well. The radiographs of lower and upper jaw also
      predicted BMD equally well. Combining inner and outer regions did not improve the
      prediction of femoral and spinal BMD, but combining lower and upper jaws did.
      CONCLUSIONS: This study shows that it is possible to include parts of
      neighbouring teeth in the ROI used to assess the trabecular pattern and predict
      BMD. This simplifies the process of selecting the ROIs because no efforts have to
      be made to exclude neighbouring teeth. Combining ROIs of lower and upper jaws
      significantly improves the prediction of BMD.

PMID- 18812599
TI  - Effect of ambient light and monitor brightness and contrast settings on the
      detection of approximal caries in digital radiographs: an in vitro study.
AB  - OBJECTIVES: The aim of this study was to investigate how brightness and contrast
      settings of the display monitor and ambient light level (illuminance) in the
      viewing room affect the clinician's ability to diagnose carious lesions in
      digital radiographs. METHODS: Standardized radiographs were taken of 100
      extracted teeth. Seven observers evaluated the images for approximal carious
      lesions twice, once under 50 lux and once under 1000 lux room illumination.
      Monitor brightness and contrast were varied +/-50% and +/-6%, respectively, to
      mimic the normal limits of monitor adjustment by an inexperienced user and one
      optimal setting. This was done by adjusting radiograph brightness and contrast by
      +/-25%. Thus, five radiographs of each tooth were evaluated. Receiver operating
      characteristic (ROC) analyses were performed. Histological examinations of the
      teeth served as the criterion standard. A paired t-test was used to evaluate
      whether differences in the areas under the ROC curves were significant and kappa
      was used to evaluate intraobserver agreement. RESULTS: When a monitor with
      optimal brightness and contrast settings was used to detect approximal carious
      lesions, ambient light levels less than 50 lux were significantly better than
      levels above 1000 lux (dentin and enamel lesions, P < 0.01; dentin lesions, P <
      0.02). Increasing the contrast setting of the monitor by 6% did not change these
      results; 50 lux was still significantly better than 1000 lux (enamel lesions, P <
      0.01; dentin and enamel lesions, P < 0.02) for evaluating radiographs.
      Intraobserver agreement differed from fair to good. CONCLUSIONS: Reducing ambient
      light to less than 50 lux significantly increased the accuracy of diagnosing
      approximal carious lesions on a monitor with an optimal brightness setting and an
      optimal or slightly higher than optimal contrast setting.

PMID- 18812600
TI  - Quantitative measurements obtained by micro-computed tomography and confocal
      laser scanning microscopy.
AB  - OBJECTIVES: To compare measurements obtained by micro-CT with those obtained by
      confocal laser scanning microscope in simulative internal resorption cavities.
      METHODS: An extracted human maxillary central incisor tooth was divided into two
      in the coronal plane. Four artificial internal resorption cavities were prepared
      with standardized burs on each section, and diameters and volumes were measured
      using a laser scanning electron confocal microscope and a desktop cone beam micro
      CT-40. Differences between means of quantitative measurements for both methods
      were tested using the paired t-test; the correlation between quantitative
      measurements was tested by regression analysis. RESULTS: Mean diameter and volume
      differences between the two methods were 0.061 mm and 0.004 mm(3), respectively.
      Average diameter and volume calculations obtained by micro-CT were significantly
      lower (P < 0.001 for diameter and P < 0.01 for volume). A significantly strong
      relationship was found in the average diameters (R(2) = 92.9%) and calculated
      volumes (R(2) = 91%), (P < 0.001). CONCLUSIONS: Although a strong correlation
      between both methods was found, micro-CT significantly underestimated the
      diameters and volumes.

PMID- 18812601
TI  - Retrospective study of the effectiveness of high-resolution ultrasound compared
      with sialography in the diagnosis of Sjogren's syndrome.
AB  - OBJECTIVE: This report aimed to evaluate the effectiveness of high-resolution
      ultrasound compared with conventional sialography in the diagnosis of Sjogren's
      syndrome (SS) and to establish whether less invasive ultrasound could replace
      sialography as a diagnostic investigation. METHOD: Clinical records and
      examination results of 105 consecutive subjects investigated contemporaneously by
      ultrasound and sialography of the parotid glands for SS were reviewed
      retrospectively. Results were compared against the final diagnosis established on
      the basis of revised international classification criteria for SS. 45 subjects
      were excluded from the study due to incomplete records. Of 60 remaining subjects
      under investigation for SS, 45 were confirmed (36 primary SS, 9 secondary SS),
      the remaining 15 subjects being proven not to have the condition. RESULTS:
      Ultrasound showed a decreased and heterogeneous honeycomb pattern of parotid
      gland reflectivity in patients with SS, while sialography demonstrated a punctate
      pattern of sialectasis. Sensitivity, specificity and accuracy for ultrasound were
      84.44%, 73% and 81.6%, respectively, and for conventional sialography were
      77.77%, 86.66% and 80%, respectively. The diagnostic difference between the two
      investigations approached significance (P = 0.074). By combining both imaging
      modalities, sensitivity increased to 91% with 60% specificity and 83.3% accuracy.
      There was no significant difference between investigations when diagnosing
      primary vs secondary SS. CONCLUSION: High-resolution ultrasound is a useful, non
      invasive and more sensitive alternative to sialography as a diagnostic test in
      patients with suspected SS. Accuracy may be increased by supplementing ultrasound
      with sialography.

PMID- 18812602
TI  - Genotoxic effects of X-rays on keratinized mucosa cells during panoramic dental
      radiography.
AB  - OBJECTIVES: The aim of this study was to evaluate the genotoxic effects of X-rays
      on epithelial gingival cells during panoramic dental radiography using a
      differentiated protocol for the micronucleus test. METHODS: 40 healthy
      individuals who underwent this procedure for diagnostic purposes on request from
      their dentists agreed to participate in this study. All of them answered a
      questionnaire before the examination. Epithelial gingival cells were obtained
      from the keratinized mucosa of the upper dental arcade by gentle scraping with a
      cervical brush immediately before exposure and 10 days later. Cytological
      preparations were stained according to the Feulgen-Rossenbeck reaction,
      counterstained with fast green 1% for 1 min and analysed under a light
      microscope. Micronuclei, nuclear projections (broken eggs) and degenerative
      nuclear alterations (pyknosis, karyolysis, karyorrhexis and condensed chromatin)
      were scored. RESULTS: The frequency of micronuclei was significantly higher after
      exposure (P < 0.05), as were the frequencies of nuclear alterations indicative of
      apoptosis (P < 0.001). CONCLUSIONS: These results indicate that X-ray radiation
      emitted during panoramic dental radiography induces a genotoxic effect on
      epithelial gingival cells that increases the frequency of chromosomal damage and
      nuclear alterations indicative of apoptosis.

PMID- 18812603
TI  - Cytogenetic biomonitoring in patients exposed to dental X-rays: comparison
      between adults and children.
AB  - OBJECTIVES: The aim of the present study was to comparatively evaluate the DNA
      damage (micronucleus) and cellular death (pyknosis, karyolysis and karyorrhexis)
      of exfoliated buccal mucosa cells from children and adults following dental X-ray
      exposure. METHODS: A total of 17 adults and 17 children submitted to panoramic
      dental radiography were included in this study. RESULTS: The results indicated no
      statistically significant differences (P > 0.05) in children's micronucleated
      oral mucosa cells before and after dental X-ray exposure. In the same way, no
      mutagenic effects were observed in adults following X-ray exposure. On the other
      hand, X-rays increased other nuclear alterations closely related to cytotoxicity
      such as karyorrhexis, pyknosis and karyolysis in both groups. The comparative
      analysis between children and adults demonstrated no statistically significant
      differences in micronucleus frequency or cytotoxicity (P > 0.05). CONCLUSIONS: In
      summary, these data indicate that dental paroramic radiography may not be a
      factor that induces chromosomal damage, but it is able to promote cytotoxicity.
      It seems that children are not more susceptible to the noxious activities induced
      by X-rays when compared with adults.

PMID- 18812604
TI  - Desmoplastic fibroma of the mandible.
AB  - Desmoplastic fibroma (DF) of the bone, also know as desmoid tumour, is a rare non
      metastasizing but locally aggressive tumour. In this case report, we present
      imaging findings of a histopathologically proven desmoplastic fibroma involving
      the left mandibular region in a 15-year-old Chinese patient. We have also
      discussed the usefulness of different imaging modalities (plain film radiography,
      CT and MRI) in DF diagnosis and treatment.

PMID- 18812605
TI  - Recurrent peripheral odontogenic keratocyst: a case report.
AB  - A case of peripheral odontogenic keratocyst arising in a 57-year-old white female
      patient involving the posterior mandibular gingiva that recurred after 12 months
      of follow-up is presented. This reported case reinforces that patients presenting
      peripheral odontogenic keratocyst should be carefully followed up after
      conservative surgical treatment.

PMID- 18812606
TI  - Primary tuberculous osteomyelitis of the mandible: a case report.
AB  - A 10-year-old female child presented with a gradually increasing swelling of 2
      months' duration on the left side of her face. The history given by the guardian
      was not very specific. However, the history revealed possible contact between the
      child and a tuberculous patient. The initial clinical and radiological evaluation
      indicated either a chronic residual dentoalveolar abscess, tuberculosis (TB) of
      the mandible or a malignancy. Routine laboratory investigations were grossly
      unremarkable with only the erythrocyte sedimentation rate being mildly raised.
      Further investigations were carried out, including a purified protein derivative
      test, chest screening, sputum examination, enzyme-linked immunosorbent assay for
      HIV and abdominal ultrasound, which were all negative. CT of the mandible showed
      a soft tissue mass in the submandibular region with an osteolytic lesion in the
      body of the mandible on the left side, and fine needle aspiration cytology (FNAC)
      showed the presence of a tuberculoid granuloma. FNAC, along with the clinical and
      radiographic findings and history, led to the diagnosis of primary TB of the
      mandible. Although FNAC is not as effective as an actual biopsy, it is often
      adequate for diagnosis and avoids a major surgical operation, which would be
      required for obtaining tissue for a biopsy. This case emphasises the role of
      proper history taking, diagnostic work-up and management. It also draws attention
      to the literature pertaining to the diagnosis of TB based on FNAC, especially in
      TB endemic areas where sophisticated tests such as the polymerase chain reaction
      are either unavailable or unaffordable.

PMID- 18812607
TI  - Adenoid cystic carcinoma of sublingual gland involving the submandibular duct.
AB  - We report an unusual case of adenoid cystic carcinoma (ACC) arising in the
      sublingual gland and extending into the submandibular duct. Our article mainly
      describes the MR findings. The margin of the mass was well-defined and the mass
      was divided into two parts - anterior and posterior. The anterior part of the
      mass showed isointense to surrounding muscle on T(1) weighted images and
      hyperintense on fat-saturated T(2) weighted images. The posterior part of the
      mass showed hyperintense both on T(1) weighted and fat-saturated T(2) weighted
      images. The findings indicated that the cystic space of the posterior part was
      filled with tumour mass which extended from the anterior part. ACC of the
      sublingual gland extending into the submandibular duct is rare and the MR
      findings have not been previously described in the literature.

PMID- 18812608
TI  - Safety, tolerability, pharmacokinetics, and pharmacodynamics of single oral doses
      of BI 1356, an inhibitor of dipeptidyl peptidase 4, in healthy male volunteers.
AB  - This randomized, double-blind, parallel, placebo-controlled, single rising-dose
      study investigated the safety, tolerability, pharmacokinetic, and pharmacodynamic
      profiles of BI 1356 (once-daily, given orally) in healthy men. BI 1356 was well
      tolerated and safe up to and including a dose of 600 mg. The incidence of drug
      related adverse events was equal in subjects receiving BI 1356 (30%) or placebo
      (31%). No clinically relevant deviations in laboratory or ECG parameters were
      reported. Exposure of BI 1356 increased less than proportionally from 2.5 mg to 5
      mg, more than proportionally from 25 mg to 100 mg and approximately
      proportionally for doses from 100 mg to 600 mg. The geometric mean terminal half
      life was up to 184 hours. Renal excretion was low. All doses of BI 1356 inhibited
      plasma dipeptidyl peptidase 4 activity. Single doses of 2.5 mg and 5 mg inhibited
      dipeptidyl peptidase 4 activity by 72.7% and 86.1% from baseline, respectively.
      The time to achieve maximum inhibition shifted with increasing doses from 3 hours
      (2.5 mg) to <0.7 hours (> or =200 mg). Within the dose range tested, a direct
      pharmacokinetic/pharmacodynamic relationship was observed. The pharmacokinetic
      and pharmacodynamic profile results demonstrate the potency and full 24-hour
      duration of action of BI 1356. Based on an estimated therapeutic dose of 5 mg,
      the therapeutic window of BI 1356 is expected to be >100-fold.

PMID- 18812609
TI  - A phase I, single and fractionated, ascending-dose study evaluating the safety,
      pharmacokinetics, pharmacodynamics, and immunogenicity of an erythropoietin
      mimetic antibody fusion protein (CNTO 528) in healthy male subjects.
AB  - The erythropoietin mimetic antibody fusion protein CNTO 528 was developed as a
      novel antibody fusion protein by constructing an active hematopoietic peptide
      onto an IgG1-based scaffold. This resulted in a molecule with a long circulating
      half-life and a prolonged effect of stimulating reticulocyte production and
      hemoglobin (Hgb) synthesis. To assess the safety, pharmacokinetics, and
      pharmacodynamics of CNTO 528, the authors gave 44 adult healthy male subjects
      single or fractionated doses of intravenous CNTO 528 or placebo. CNTO 528 was
      generally well tolerated. The maximum observed concentration (Cmax) and the area
      under the concentration versus time curve (AUC) increased in an approximately
      dose-dependent manner between the 0.09-mg/kg and 0.9-mg/kg doses. The maximum
      effect on the reticulocyte response occurred approximately 8 to 9 days after
      administration. A median increase in Hgb (> or =1 g/dL above baseline) was
      achieved 9 to 10 days after administration, with a maximum effect between 19 and
      26 days. Two subjects in the 0.9-mg/kg dose group had elevated Hgb concentrations
      requiring phlebotomy. In this first-in-human study, CNTO 528 was well tolerated
      and effective in elevating and maintaining Hgb by at least 1 g/dL following a
      single intravenous administration, which suggests that an erythropoietin mimetic
      molecule, such as CNTO 528, may be an effective therapy for patients with anemia.

PMID- 18812610
TI  - Drug-binding cavities in long-lived biologics: cause for concern but also
      potential benefit.
AB  - Universally present but overlooked cavities or pockets in long-lived
      biopharmaceuticals, such as monoclonal antibodies (mAbs), are capable of binding
      small drugs. Such direct interactions can alter the pharmacokinetics of drugs and
      potentially affect clinical outcome. The extreme differences in the
      pharmacokinetic properties of these 2 classes of drugs largely account for such
      effects. This overlooked mechanism of biologic-chemical drug interaction should
      be considered before approval of new long-lived entities.

PMID- 18812611
TI  - Pharmacologic consideration for the use of antiretroviral agents in the elderly.
AB  - The prevalence of human immunodeficiency virus (HIV) infection among people older
      than 50 years is increasing. HIV-infected patients require lifelong treatment
      with antiretroviral agents to suppress viral replication and maintain immune
      function. The use of antiretroviral agents in the elderly can be complicated by
      multiple chronic comorbidities and coadministered non-HIV medications. The
      pharmacokinetics of antiretroviral agents may be altered due to age-related
      decrements in hepatic and renal function. The elderly may be more sensitive than
      younger people to antiretroviral drug toxicity. A better understanding of the
      pharmacokinetics of antiretroviral agents in the elderly is of importance for the
      successful management of complex antiretroviral regimens in this population.

PMID- 18812612
TI  - Estimation of creatinine clearance.

PMID- 18812614
TI  - Telehospice acceptance among providers: a multidisciplinary comparison.
AB  - Telehospice, the delivery of end-of-life care using telecommunications
      technologies, allows increased interaction between providers and patients. For
      telehospice to be successful, it must first be accepted by professionals as a
      useful and user-friendly method of service delivery. Existing research regarding
      provider acceptance of telehospice has been limited in geographic scope and has
      often excluded input from key members of the hospice team. This study measured
      telehospice acceptance in a national sample of hospice professionals from various
      disciplines (N = 160). Results indicate that acceptance was moderately high
      overall, although significant differences existed among individuals from
      different disciplines, with nurses and administrators generally indicating higher
      levels of acceptance than social workers and chaplains. Findings demonstrate that
      telehospice interventions will likely be more readily accepted by nursing and
      administrative staff members, while those employees who address primarily
      psychosocial issues may be reluctant to use such technology.

PMID- 18812615
TI  - Pain management practices by internal medicine residents--a comparison before and
      after educational and institutional interventions.
AB  - We aimed to improve internal medicine residents' deficiencies in pain management
      and evaluate the effectiveness of our intervention, which included an interactive
      conference series, e-mail vignettes, and didactic sessions. An anonymous survey
      was administered at the beginning and at the end of an academic year, before and
      after the intervention, respectively. We analyzed 65 preintervention and 63
      postintervention surveys. Self-perception of competency in pain management
      increased from 40% to 60% (P = .02). Perception of adequacy of training increased
      from 38.5% to 55.6% (P = .05). Opioid conversion skills improved by 25% (P =
      .02). Overall, knowledge did not change significantly, except in the subgroup of
      residents who had completed the oncology rotation from 0.60 to 0.72 (P = .003).
      "Opiophobia'' improved by 20% (P = .05). Documentation of pain improved (rank
      correlation = 21; P = .02). We concluded that educational and institutional
      interventions administered over an academic year improved pain management skills
      and documentation and reduced "opiophobia'' among residents.

PMID- 18812616
TI  - Comorbidities in a cancer patient: problems in pain management and palliation.
AB  - Pain management and palliation face a great challenge with inclusion of the
      palliation teams from the earliest phases of diagnosis. The presented case report
      highlights that early inclusion of pain and palliative physicians in patient care
      demands comprehensive evaluation of the symptoms by the palliative physicians
      with possibly curable comorbid conditions requiring active and aggressive
      curative management. In summary, it is crucial for the treating palliative
      physician to be more proactive in the management of comorbid treatable conditions
      in a patient who may be an established case of advanced stage cancer.

PMID- 18812617
TI  - The use of pediatric advance directives: a tool for palliative care physicians.
AB  - Although laws such as the Patient Self-Determination Act encourage individuals to
      address their end-of-life treatment preferences using advance directives, the
      wishes of children have traditionally been ignored or, perhaps even worse,
      overruled. Given that there is a substantial body of research indicating that
      children are capable of making mature decisions when faced with terminal illness,
      the author proposes granting minors, especially older minors, the right to
      participate in making end-of-life decisions. Children who complete advance
      directives benefit in multiple ways. Adopting this approach could benefit
      patients by demonstrating respect for patient autonomy and informing parents and
      providers that the minor may be ready to stop aggressive treatment.

PMID- 18812618
TI  - Management of patients with ICDs at the end of life (EOL): a qualitative study.
AB  - PURPOSE: Implantable cardioverter defibrillator shocks at the end of life are
      distressing and warrant consideration of implantable cardioverter defibrillator
      deactivation discussions. A nationwide survey collected physicians' comments
      regarding such discussions. METHODS: Vignettes ascertained respondents' practices
      regarding implantable cardioverter defibrillator deactivation discussions.
      Respondents' comments were analyzed to identify themes. RESULTS: About 177
      respondents (32%) provided 310 comments. One third reported that initiating the
      discussion would depend on specific circumstances, such as do not resuscitate
      status (35%); 21% advocated life-prolonging therapies; 17% said the
      patient/family or another physician should initiate the discussion; and 9%
      expressed inadequate education/awareness about implantable cardioverter
      defibrillator functions. Geriatricians and general internists expressed
      inadequate knowledge most frequently (12 writers, 75% in this theme), while
      electrophysiologists most frequently suggested further treatments/procedures (22
      writers, 58%), and another doctor (13 writers, 76%) or the patient (8 writers,
      62%) should begin the discussion. CONCLUSIONS: Improving the end of life care for
      patients with implantable cardioverter defibrillators will require additional
      physician education and increased commitment by subspecialists to deactivation
      discussions.

PMID- 18812619
TI  - End-of-life care curricula in undergraduate medical education: a comparison of
      allopathic and osteopathic medical schools.
AB  - End-of-life care curricula in osteopathic medical schools were compared with
      allopathic school offerings. An 8-question online survey of undergraduate medical
      education administrators at all United States osteopathic medical schools (n =
      26) and 26 allopathic schools geographically closest to them was conducted in
      2007. Responses from 80% (n = 21) of osteopathic schools and 77% (n = 20) of
      allopathic schools revealed that both osteopathic and allopathic medical schools
      offered end-of-life care education. Of note is that 71% of the osteopathic
      medical school respondents had a course that concentrates on end-of-life care
      compared with 37% of allopathic school respondents (P = .03). This disparity in
      percentages may be due to a number of reasons, 2 of which may include course
      identification methods and the primary care orientation and philosophy inherent
      in osteopathic medical schools.

PMID- 18812620
TI  - Uncovering beliefs and barriers: staff attitudes related to advance directives.
AB  - Although the 1990 Patient Self-determination Act was enacted to insure that
      patients' wishes regarding advance directives were known and respected, it has
      had little impact in quality or aggressiveness of care for patients nearing
      death. The purpose of this descriptive study was to explore staff attitudes
      related to Advance Directives. A short survey was distributed to 650 hospital,
      home care, hospice, assisted living, and long term professional and staff
      members. Analysis was completed on 413 surveys (return rate 63.3%). Findings
      suggest that although staff members believe that Advance Directives are an
      important tool, they have found both logistical and process challenges to
      following them. The results provide needed information for improving processes
      for completion and utilization of Advance Directives.

PMID- 18812621
TI  - Isolation of human monoclonal antibodies by mammalian cell display.
AB  - Due to their low immunogenicity in patients, humanized or fully human mAbs are
      becoming increasingly important for the treatment of a growing number of
      diseases, including cancer, infections, and immune disorders. Here, we describe a
      technology allowing for the rapid isolation of fully human mAbs. In contrast to
      previously described methods, B cells specific for an antigen of interest are
      directly isolated from peripheral blood mononuclear cells (PBMC) of human donors.
      Recombinant, antigen-specific single-chain Fv (scFv) libraries are generated from
      this pool of B cells and screened by mammalian cell surface display by using a
      Sindbis virus expression system. This method allows isolating antigen-specific
      antibodies by a single round of FACS. The variable regions (VRs) of the heavy
      chains (HCs) and light chains (LCs) are isolated from positive clones and
      recombinant fully human antibodies produced as whole IgG or Fab fragments. In
      this manner, several hypermutated high-affinity antibodies binding the Qbeta
      virus like particle (VLP), a model viral antigen, as well as antibodies specific
      for nicotine were isolated. All antibodies showed high expression levels in cell
      culture. The human nicotine-specific mAbs were validated preclinically in a mouse
      model. Thus, the technology presented here allows for rapid isolation of high
      affinity, fully human antibodies with therapeutic potential from human
      volunteers.

PMID- 18812622
TI  - The standing heel-rise test: relation to chronic venous disorders and balance,
      gait, and walk time in injection drug users.
AB  - Injection drug use can impair mobility. When mobility is impaired in combination
      with other potential pathologic changes to the veins, muscles, and joints of the
      lower legs, chronic venous disorders can develop. The heel-rise test, an
      assessment of eccentric-concentric muscle action of calf muscle function with
      regard to plantar flexion, can be used to measure ankle mobility. To examine the
      test-retest reliability and construct validity of the heel-rise test in relation
      to chronic venous disorders in persons with a history of injection drug use (N =
      104), a test-retest study (M = 45.9+/-12.9 days from first to second test) was
      conducted. Participants were assessed for chronic venous disorders of the legs
      and walk time; they also completed the heel-rise and Tinetti Balance and Gait
      tests. Test-retest reliability was found to be good for full heel rise of right
      and left legs (ICC = .66 and .67, respectively). Heel-rise performance was
      positively correlated with balance (r = .38 to .47) and gait (r = .38 to .45) and
      negatively related to walk time (r = -.30 to -.35) (P <0.01). Participants who
      injected in the groin, legs, or feet performed fewer heel rises than those who
      injected in the arms and upper body only or those who did not inject drugs.
      Chronic venous disorders accounted for 7% to 17% of the variance in heel rise.
      The heel-rise test as a measure of calf muscle function is supported by these
      results, implicating the role of mobility restriction in the etiology of venous
      disease. Although more research is needed regarding its performance, the heel
      rise test may be a low-cost, noninvasive screening or assessment tool in a
      variety of outpatient settings.

PMID- 18812623
TI  - The nutritional status of older adults with and without venous ulcers: a
      comparative, descriptive study.
AB  - The nutritional requirements of healthy people differ from those who have chronic
      wounds and while it is generally suggested that the nutritional status of persons
      with chronic wounds must be addressed, actual data about the nutritional status
      of older adults with venous ulcers is limited. The nutritional status of
      hospitalized older adults (n = 40, average age 77 +/- 7.4) with vascular disease
      was compared to randomly selected outpatients with venous insufficiency ulcers (n
      = 37, average age 70.4 +/- 8.13) using the Mini Nutritional Assessment
      instrument. Among all patients assessed, 37 (48%) were at risk for malnutrition
      or were malnourished. No differences between nutritional status and age or gender
      were found. The proportion of patients at risk for malnutrition or currently
      malnourished was significantly higher in the venous ulcer (24 out of 37) than in
      the control group (13 of 40, chi2 = 15.51, P <0.05). Statistically significant
      differences were found between the control and venous ulcer group for all
      anthropometrical assessment variables (BMI, arm circumference, calf
      circumference, and weight loss in past 3 months), use of more than three
      prescription drugs, dietary history/assessment (appetite, fluid consumption,
      independent feeding), and patient self-rated health. The results of this study
      confirm that a complete patient assessment must include evaluating patient
      nutritional status and that nutritional disorders are a serious problem among the
      elderly, especially those with venous ulcers. Additional studies to help optimize
      the nutritional assessment and management of older adults with venous ulcers are
      needed.

PMID- 18812624
TI  - Management of abdominal wound dehiscence with porcine dermal collagen implant:
      report of a case.
AB  - Abdominal wound dehiscence is a major postoperative complication with a high
      mortality rate. Although the mainstay of management is immediate operative
      reclosure, critically ill patients are better served by conservative temporary
      measures and delayed operative closure. The evidence in the literature regarding
      the use of biosynthetic implants in abdominal wound dehiscence is limited. To
      expand knowledge of management options, a case of abdominal wound dehiscence post
      hysterectomy in a critically ill 69-year-old woman managed with placement of a
      porcine dermal collagen implant is described. The porcine dermal collagen implant
      was placed in an infected field for the repair of the fascial defect under local
      anesthesia. No additional surgery was required and, 9 months post surgery, the
      patient remained healthy without evidence of residual hernia. Biosynthetic
      implants may be an effective alternative for the acute management of fascial
      dehiscence in critically ill patients.

PMID- 18812625
TI  - Negative pressure wound therapy combined with acoustic pressure wound therapy for
      infected post surgery wounds: a case series.
AB  - Acute infection of surgical incision sites often requires specialized wound care
      in preparation for surgical closure. Optimal therapy for preparing such wounds
      for a secondary closure procedure remains uncertain. The authors report wound
      outcomes after administering acoustic pressure wound therapy in conjunction with
      negative pressure wound therapy with reticulated open-cell foam dressing changes
      to assist with bacteria removal from open, infected surgical-incision sites in
      preparation for secondary surgical closure in three patients. Before
      incorporating acoustic pressure wound therapy at the authors' facility, the
      average negative pressure wound therapy with reticulated open-cell foam dressing
      course prior to secondary surgical closure was 30 days; with its addition, two of
      three patients underwent successful surgical closure with no postoperative
      complications after 21 and 14 days, respectively; one patient succumbed to
      nonwound-related complications before wound closure. Larger, prospective studies
      are needed to evaluate combining negative pressure wound therapy with reticulated
      open-cell foam dressing and acoustic pressure wound therapy for infected, acute
      post surgery wounds.

PMID- 18812626
TI  - Brain-gut and appetite regulating hormones in the control of gastric secretion
      and mucosal protection.
AB  - The progress in basic and clinical gastrology indicates that gastric mucosal
      integrity represents a balance between offensive and defensive factors. The main
      offensive factors appear to be gastric acid and pepsin under health conditions,
      while the nonsteroidal anti-inflammatory drugs (NSAID) and Helicobacter pylori
      (H. pylori), infecting this mucosa, are currently considered the most important
      "aggressive" factors under pathological conditions. To the list of the aggressive
      factors, also stress, certain cytokines (TNF-alpha, IL-8, IL-11 and IL-18) and
      oxygen or nitrogen free radicals should be added. The aims of this review is the
      presentation of the involvement of aggressive and protective factors in the
      control of gastric acid secretion and appetite regulating hormones in maintaining
      gastric mucosal integrity and its protection against damaging factors.

PMID- 18812627
TI  - Thirty four years since the discovery of gastrointestinal melatonin.
AB  - After the discovery of melatonin in the pineal gland by Lerner and co-workers in
      1958, melatonin was also detected in the retina and the human appendix. Later,
      melatonin was confirmed immunohistologically in all segments of the
      gastrointestinal tract (GIT), in the guts of bovine embryos and in the GIT of low
      vertebrates. Melatonin was also confirmed in the pancreas and the hepatobiliary
      system. Melatonin is produced in the enteroendocrine cells of the GIT mucosa. The
      concentrations of melatonin in the GIT are 10-100x higher than in the plasma and
      the total amount of melatonin in the GIT is around 400x higher than the amount of
      melatonin in the pineal gland. Similar to pineal melatonin, GIT melatonin is a
      multifunctional compound which exhibits some general as well as some specific
      effects, depending on the organ and the location of GIT tissue. In the GIT,
      melatonin exhibits endocrine, paracrine, autocrine and luminal actions.
      Generally, the episodic secretion of melatonin from the GIT is related to the
      intake and digestion of food and to the prevention of tissue damage caused by
      hydrochloric acid and digestive enzymes. Some actions, such as the scavenging of
      hydroxyl free radicals, immunoenhancement and antioxidant effects are of general
      nature, whereas others, such as an increase of mucosal blood flow, the reduction
      of peristalsis and the regulation of fecal water content, are specific to the
      tubular GIT. Generally, melatonin actions oppose those of serotonin. Laboratory
      and clinical studies indicate that the utilization of melatonin can prevent or
      treat pathological conditions such as esophageal and gastric ulcers,
      pancreatitis, colitis, irritable bowel disease, and colon cancer.

PMID- 18812628
TI  - Tryptophan free diet delays healing of chronic gastric ulcers in rat.
AB  - Melatonin (MT) is an ubiquitous molecule, representing one of the
      phylogenetically oldest signaling mechanisms. Our previous studies demonstrated
      that MT and its precursor L-tryptophan (L-Trp) show strong protective effect on
      gastric mucosa. The aim of the present study was: 1) to assess the effect of MT
      and L-Trp on healing of chronic gastric ulcer and accompanying changes in gastric
      mucosal blood flow (GBF); 2) to study the effect of MT and L-Trp on expression of
      iNOS. cNOS and HSP70 in ulcerated mucosa; 3) to compare the effect of L-Trp free
      and L-Trp rich diet on ulcer healing and gene expression of proinflammatory
      cytokines such as tumor necrosis factor-alpha (TNF-alpha), superoxide dismutase
      (SOD), cyclooxygenase-2 (COX-2) and NFkappaB-p65 protein expression in ulcer area
      and intact non-ulcerated. Chronic ulcers were induced in Wistar rats by Okabe's
      modification of acetic acid method. Rats with chronic gastric ulcers were divided
      in following treatment groups: 1) vehicle (saline); 2) MT (20mg/kg-d i.p.) and 3)
      L-Trp (100 mg/kg i.p.). The expression of iNOS, cNOS and HSP70 protein was
      measured by Western blot. In separate experiments, the influence of commercially
      available (Bio-Serv, USA) L-Trp free diet (TFD) was compared to the L-Trp rich
      diet (TRD) on the course of ulcer healing was assessed. The ulcer area was
      measured by planimetry. The expression of TNFalpha, COX-2 and SOD mRNA in
      ulcerated mucosa was analyzed by RT-PCR method. MT and its precursor L-Trp
      significantly accelerated ulcer healing. Healing ulcerated mucosa showed
      increased protein expression of iNOS and HSP70 as compared to intact gastric
      mucosa. TFD in contrast to normal diet significantly attenuated the ulcer
      healing, whereas the TRD exerted opposite effects and significantly accelerated
      ulcer healing. This last effect was accompanied by significant decrease of TNF
      alpha mRNA expression and expression of NFkB-p65 in gastric mucosa. We conclude
      that: 1) MT and its precursor L-Trp significantly accelerate healing of gastric
      ulcer; 2) L-Trp free diet significantly attenuates experimental ulcer healing and
      this is due to decreased synthesis of MT from L-Trp by EE cells in gastric mucosa
      and 3) MT shows strong anti-inflammatory effects due to inhibition of NFkappaB
      and TNF-alpha expression.

PMID- 18812629
TI  - Melatonin and its precursor L-tryptophan prevent acute gastric mucosal damage
      induced by aspirin in humans.
AB  - Melatonin (MT) and its precursor L-tryptophan (Trp) are implicated in the
      protection of gastric mucosa against noxious agents. However, the role of MT and
      Trp on the gastric mucosal injury induced by aspirin (ASA) in human has not been
      investigated. Studies in animals showed that both MT and Trp given
      intragastrically prevents the formation of gastric mucosal lesions induced by
      ASA. The aim of the present study was to determine the influence of MT and Trp
      given orally to healthy humans on gastric mucosal lesions induced by ASA. The
      present study included 21 healthy, Hp-negative male volunteers with intact gastro
      duodenal mucosa aging 20-50 yr. They were divided in 3 groups; group 1: 7
      volunteers receiving daily 2 x 1g ASA (Polfa, Rzeszow) during 11 days; group 2: 7
      healthy volunteers receiving 2x1 g ASA and MT (Lekam, Zakroczyn) (5 mg 30 min
      prior to ASA) during 11 days and group 3: 7 healthy volunteers receiving 2x1 g
      ASA and Trp (Ardeytropin, Germany) (0.5 g 30 min prior to ASA) during 11 days.
      Mucosal damage was evaluated at 3(rd), 7(th) and 11(th) days of ASA
      administration by endoscopy using Lanza score. Plasma melatonin was measured
      using RIA and gastric mucosal generation of PGE(2) was assessed also by RIA. ASA
      caused marked mucosal injury at all days of its administration except day 11(th)
      when only moderate lesions were evident. Pretreatment with MT or Trp alone was
      accompanied by a significant decrease in gastric mucosal lesion score. Gastric
      mucosal generation of PGE(2) was suppressed by about 90% in subjects treated with
      ASA without or with MT or Trp. We concluded that: MT and its precursor Trp
      significantly attenuate gastric mucosal lesions induced by aspirin. The action of
      Trp may be be mediated by MT produced in gastrointestinal tract from Trp. The
      gastroprotective action of MT and Trp is independent on gastric mucosal PGE2
      generation.

PMID- 18812630
TI  - Effects of nitrosative stress and reactive oxygen-scavenging systems in
      esophageal physiopathy under streptozotocin-induced experimental hyperglycemia.
AB  - Experimental and clinical gastrointestinal data reported that nitrosative stress
      development involved in impaired barrier function, altered motility and a lowered
      threshold to noxious stimuli, but its pathogenetic role in diabetic esophagopathy
      remains unexplored. We tested the hypothesis that an imbalance in nonenzymatic
      glycation and glycooxidation, enhanced peroxynitrite formation, may play an
      important role in development esophageal mucosa (EM) lesions during
      streptozotocin-induced experimental hyperglycemia (EHG). To understand the
      biological significance of EM resistance in vivo used a glycomic approach to
      identification of lectin receptors glycosylation pattern. Were enrolled rat
      groups without/with EHG & modification of NO/NOS activity by L-arginine (L-arg)
      and indomethacin pre-treatment. Survival rate, destruction occurrence ratio, the
      size of EM lesions, and the number of EM lesions was investigated. To access the
      oligosaccharide residues the peroxidase conjugated lectin (HPA, SNA, WGA, PNA)
      diaminobenzidine procedure was performed to EM sections. EHG was monitored daily
      by glucometer. Content of NO (NO(n)) was determinated by Griess reagent and
      reactive oxygen-scavenging systems (ROSS) activity - generally accepted
      biochemical methods. In EHG and L-arg pretreatment group reduced NO(n) and EM
      injury with markedly rise ROSS activity significantly vs to control; in the group
      with indomethacin pretreatment existed different ROSS activity. Presence of
      heterogeneous glycosylation pattern in different layers of EM was shown. In EHG
      staining with PNA and SNA were strongly positive. NS and ROSS play a critical
      role in esophagoprotection induced by EHG, because both involved increases in
      iNOS expression. These results indicate the usefulness of glycomic approach as
      multifunctional substrate of early evaluation of NS in esophageal physiopathy.

PMID- 18812631
TI  - Physiological mediators in nonsteroidal anti-inflammatory drugs (NSAIDs)-induced
      impairment of gastric mucosal defense and adaptation. Focus on nitric oxide and
      lipoxins.
AB  - Prostaglandins mediate various physiological aspects of mucosal defense and the
      suppression of prostaglandin synthesis in the stomach is a critical event in
      terms of the development of mucosal injury after NSAID administration. However,
      it has become clear that other mediators besides prostaglandins can similarly act
      to protect the stomach from injury. For instance, nitric oxide (NO) released from
      vascular epithelium, epithelial cells of gastrointestinal tract and sensory
      nerves can influence many of the same components of mucosal defense as do
      prostaglandins. Thus, administration of NO in a form of NO-donors exert
      protective influence on the stomach from the injury that usually occurs when
      mucosal prostaglandin levels are suppressed. The new class of NO releasing
      NSAIDs, including NO-aspirin, represent a very promising approach to reducing the
      toxicity of anti-inflammatory drugs. Lipoxins are another group of lipid
      mediators that can protect the stomach. Aspirin-triggered lipoxin synthesis, via
      COX-2, acts to reduce the severity of damage induced by this drug. Lipoxin
      analogues may prove to be useful for preventing mucosal injury and for modulating
      mucosal inflammation. Aspirin-triggered lipoxin also seems to play in important
      role in gastric adaptation during chronic aspirin administration. Suppression of
      COX-2 activity by selective COX-2 inhibitors abolishes the production of this
      endogenous gastroprotective substance and diminishes the gastric tolerability of
      NSAIDS and gastric adaptation to these drugs. This review was designed to give an
      updated overview on the physiological factors and experimental and clinical
      attempts that were used or may be used in the future as the therapeutic approach
      to counteract adverse effects in the stomach associated with NSAID ingestion.

PMID- 18812632
TI  - Nitric oxide (NO)-releasing aspirin and (NO) donors in protection of gastric
      mucosa against stress.
AB  - Acute gastric mucosal lesions represent an important clinical problem. The
      experimental model of acute gastritis such as water immersion restraint (WRS)
      stress is useful tool in examination of pathomechanism of acute gastric damage.
      Nitric oxide (NO) plays an important role in the maintenance of gastric barrier,
      however the role of reactive oxygen species (ROS) in the interaction between NO
      and gastric mucosa integrity has been little studied. The purpose of our present
      study was to explain the participation of ROS in healing of WRS-induced gastric
      lesions accelerated by NO. Experiments were carrying out on 120 male Wistar rats.
      To assess gastric blood flow (GBF) laser Doppler flowmeter was used. The number
      of gastric lesions was established by planimetry. The colorimetric assays were
      used to determine gastric tissue level of malondialdehyde (MDA) and 4
      hydroxynonenal (4-HNE), the products of lipid peroxidation by ROS, as well as
      superoxide dismutase (SOD) activity, the enzyme scavanger of ROS. We demonstrated
      that 3.5 h of WRS resulted in appearance of acute gastric mucosal lesions
      accompanied by a significant decrease of GBF. Biological effects of ROS were
      estimated by measuring tissue level of MDA and 4-HNE, as well as the SOD
      activity. It was demonstrated that 3.5 h of WRS led to significant increase of
      MDA and 4-HNE mucosal level, that was accompanied by a decrease of SOD activity.
      Pretreatment with NO-donors (SIN-1, SNAP, nitroglycerin, NO-ASA) resulted in
      reduction of gastric lesions number, increment of GBF, decrease of MDA and 4-HNE
      tissue level and increase of SOD activity. Suppression of ROS play an important
      role in NO-donors action in gastroprotection against gastric acute lesions
      induced by 3.5 h of WRS. NO-donors cause an attenuation of lipid peroxidation as
      documented by a decrease of MDA and 4-HNE levels and enhancement of antioxidative
      properties as evidenced by increase of SOD activity.

PMID- 18812633
TI  - Cardiovascular and gastrointestinal toxicity of selective cyclo-oxygenase-2
      inhibitors in man.
AB  - It is well established that the use of traditional nonsteroidal anti-inflammatory
      drugs (NSAIDs) increase the vulnerability of the gastrointestinal (GI) mucosa for
      the development of peptic lesions and serious ulcer complications. In addition,
      selective and traditional NSAIDs have also been associated with increased
      frequency of cardiovascular toxicity, especially in susceptible patients. The
      objective of this communication is to provide an overview of the salient GI and
      cardiovascular (CV) toxicity for these drugs. Traditional NSAIDs inhibit the
      constitutional cyclooxygenase-1 (COX-1) enzyme responsible for eicosanoids
      biosynthesis not only in joints, a beneficial effect, but also in the stomach, a
      detrimental effect. Selective NSAIDs were specifically designed to preferentially
      inhibit the cyclooxygenase-2 (COX-2), an inducible enzyme mediating the
      production of inflammatory eicosanoids in the joints but sparing the endogenous
      protective eicosanoids in the stomach. Selective COX-2 inhibitors (COXIBs) have
      been shown to possess much improved GI tolerability and reduced GI related
      adverse events when compared with nonselective COX-1 inhibitors. An unexpected CV
      toxicity had emerged during the COXIBs post marketing outcome studies. Many
      subsequent studies were carried out to define the CV risks associated with COXIBs
      and NSAIDs. All COX inhibitors had shown this CV toxicity. In many clinical
      studies, rofecoxib use was associated with significantly more elevated CV risk
      when compared with celecoxib and non selective NSAIDs. The COX inhibitors
      associated CV toxicity has multiple manifestations, which include the induction
      of myocardial infarction (MI), edema, thrombosis, blood pressure destabilization
      and death. Patients at risk of CV disease or with a history of CV disease were
      the most significant determinants of CV events after receiving COX inhibitors.
      This CV toxicity not only led to the marketing withdrawal of rofecoxib and
      valdecoxib but also resulted in more restricted, but essentially identical,
      product labels in the United States for celecoxib and traditional NSAIDS. This CV
      toxicity is dose and treatment duration dependent and appears to be compound
      specific rather than COX specific. Additional comprehensive, long-term,
      prospective investigations comparing the CV and GI safety profile of marketed
      NSAIDs against each other and against selective inhibitors are needed to address
      the controversy of COX inhibitors.

PMID- 18812634
TI  - Satiety signalling histaminergic system and brain-gut peptides in regulation of
      food intake in rats with portocaval anastomosis.
AB  - Brain histamine plays a regulatory role in feeding behaviour, acting as an
      inhibitory modulator. Portocaval anastomosis (PCA) is associated with cerebral
      aminergic systems alterations, including high histamine accumulation and release
      from neurons. Despite that, the rats with PCA eat significantly more, their body
      mass being lower than sham-operated animals. To disclose underlying regulatory
      mechanisms, food intake was measured before and after treatment with antagonists
      of histamine H(1) and H(2), orexin type 1 (OX(1)) and cannabinoid type 1 (CB(1))
      receptors in adult male Lewis rats 6 months following the end-to-side PCA or sham
      operation. Hypothalamic concentrations of orexin A and histamine as well as serum
      concentrations of leptin, insulin and cholecystokinin (CCK) were analysed. PCA
      rats with body mass lower by 30%, have consumed more feed and water 150% and
      200%, respectively. The modifying effects of pyrilamine, ranitidine, SB 334867
      and rimonabant were less pronounced in PCA compared with sham-operated rats.
      Hypothalamic orexin A and histamine concentrations were higher in PCA rats than
      in the control group with intact portocaval system. In PCA rats, serum
      concentrations of CCK were higher, leptin concentrations lower, while there were
      no differences between the groups in insulin levels. In conclusion, the adaptive
      mechanisms efficiently render PCA rats less sensitive to peripheral and central
      anorexigenic signals. Orexin A appears to be involved in the counteracting
      mechanisms preventing further body mass loss in PCA rats.

PMID- 18812635
TI  - Role of feed-regulating peptides on pancreatic exocrine secretion.
AB  - In recent two decades a group of feed intake-regulating peptides (i.e., leptin,
      apelin, ghrelin, obestatin and orexins) have been discovered. Besides the central
      nervous system these regulatory peptides are produced and released by the
      gastrointestinal (GI) endocrine cells and neurons, and functional receptors were
      found in the GI tract and the pancreas. High expression of feed intake-regulating
      peptides was found in the stomach; however, they may be expressed in other GI
      tissues too. The peptides control gastrointestinal functions, modulate orexigenic
      drive and energy metabolism via different mechanisms. Basal leptin, apelin,
      ghrelin and obestatin plasma concentrations correlated with BMI, and we observed
      significant reduction of ghrelin and leptin concentrations following fundectomy
      in rats. We have shown previously that exogenous leptin and ghrelin (a peptide
      derived from the same preprohormone as obestatin) inhibit the secretion of rat
      pancreatic juice through a neurohormonal mechanism. Intravenous obestatin was
      found to stimulate pancreatic protein output in anaesthetized rat via a CCK-vagal
      dependent mechanism, whilst a direct action of obestatin on rat pancreatic acini
      in vitro resulted in opposite effect. Intravenous boluses of apelin reduced the
      juice volume, protein and trypsin outputs in a dose-dependent manner. However,
      apelin administered into the duodenal lumen significantly increased pancreatic
      protein and trypsin outputs through a vagal mechanism. Orexin A and B were found
      to stimulate insulin release, though on the rat exocrine pancreas orexin A had no
      effect, and the effect of orexin B was weak. Concluding, feed intake-regulating
      peptides participate in controlling the exocrine pancreas.

PMID- 18812636
TI  - Postprandial response of ghrelin and PYY and indices of low-grade chronic
      inflammation in lean young women with polycystic ovary syndrome.
AB  - The aim of the study were to answer the question 1.) Whether circulating pro
      inflammatory markers of endothelial dysfunction and due to chronic low-grade
      inflammation of obesity, are altered in untreated lean, young relatively healthy
      polycystic ovary syndrome (PCOS) patients in comparison with healthy controls;
      2.) Whether postprandial plasma concentration pattern of ghrelin and PYY can be
      predictable as risk factors for atherosclerosis and depend of obesity. Forty
      young women with PCOS were divided in two groups: 19 lean and 21 obese. The
      control group included 20 lean, healthy volunteers. Plasma total and active
      ghrelin, total PYY and PYY(3-36), serum adiponectin and insulin were measured
      using RIA technique, serum sCD40L, visfatin, sP-, sE-selectins, resistin by EIA.
      Composition of test meal was: 527 kcal total and consisted of 24.1% fat, 54.4%
      carbohydrate and 21.5% protein. Total and active ghrelin and total PYY were
      significantly lower in obese PCOS women, whereas active ghrelin was also
      significantly lower in lean PCOS women compared to controls. Postprandial plasma
      total ghrelin levels decrease were blunted in lean and obese compared to controls
      (12.8 % and 18.2% vs 28.2 %). Postprandial plasma active ghrelin decreased in
      lean and obese PCOS groups (49.9 % and 44.1 %) and controls (63.8 %). PCOS
      subjects exhibited smaller rises in postprandial levels of total PYY.
      Postprandial plasma PYY(3-36) levels increased in obese PCOS women (30.9 %) and
      controls (41%), whereas lean PCOS women exhibited blunted increase (11.5%).
      sCD40L levels increased, whereas adiponectin decreased in PCOS groups
      independently, whereas rise in visfatin, sE- and sP-selectin and the fall in
      adiponectin was associated with obesity. sP- and sE -selectins correlated
      positively with obesity. In summary, our study provides the first evidence that
      lean untreated young PCOS women contribute to the so called "pancreatic islet
      adaptation to insulin resistance" because of ghrelin and PYY profiles. We
      confirmed existing of low-grade chronic inflammation in early stage of visceral
      obesity in lean PCOS patients. The lost endogenous "islet adaptation to insulin
      resistance" may lead to endothelial dysfunction and promote acceleration of
      atherosclerosis.

PMID- 18812637
TI  - The role of sensory C-fibers in response of vagal afferent stimulation by gastric
      distension in rats with experimental chronic gastric ulcer.
AB  - There is growing evidence that gastric vagal afferent input may contribute to the
      altered sensations associated with gastrointestinal disorders. The aim of our
      study was to evaluate gastric vagal afferents (VA) activity in rats with
      experimental gastric ulcer and ulcer healing. The study was carried out on rats
      with gastric ulcer (GU), including, a group with perivagal capsaicin pretreatment
      (CAP), a group with capsaicin administration in gastric ulcer (CAP+GU) animals
      and control rats. In all rats electrical VA activity was recorded and analysed.
      In GU rats recordings were carried out in chronic ulcer and ulcer healing. In GU
      and CAP+GU groups gastric balloon distensions with vagal recording was performed
      on 3(rd) day after ulcer induction. Usually, experimental GU healed spontaneously
      within 2 weeks. Three days after acetic acid application when GU fully develop,
      the frequency of the basal VA activity was almost 3-times higher than in the
      control intact rats and remained elevayed until 4(th) week after ulcer induction.
      VA response to gastric distension increased concomitantly with increased balloon
      volume in both GU and control animals, but it was several times higher in GU
      rats. Perivagal capsaicin application decreased the frequency of spontaneous VA
      activity and decreased the response of VA to gastric distension. In CAP+GU,
      spontaneous activity as well as the response to gastric distension were higher
      than in CAP rats. Our study shows that GU induced inflammatory changes increase
      sensitivity of gastric VA. Capsaicin-sensitive vagal afferent fibers may play
      some role in this phenomenon. Peripheral sensitization of VA persists even when
      gastric ulcer is completely healed.

PMID- 18812638
TI  - Molecular mechanism of protection against chemically and gamma-radiation induced
      apoptosis in human colon cancer cells.
AB  - The involvement of peroxisome proliferator-activated receptors (PPARs) in the
      cancer cell elimination through apoptosis is a generally accepted fact. However,
      some reports indicate that the activation of PPARgamma is directly responsible
      for carcinogenesis. Caco-2 cells, a human adenocarcinoma cells, were used as a
      model of colon cancer. Cell cultures (5 x 10(6) cell per dish) were pretreated
      for 24 h with PPAR gamma agonists ciglitazone (CI, 1 x 10(-6)M) and retinoic acid
      (RA, 1 x 10(-6)M) and part of the cultures were subsequently subjected to gamma
      radiation (photons) with therapeutic dose of 2,5 Gy. Total cellular RNA and
      proteins (cytoplasmic and nuclear) were isolated 24h after cultures irradiation
      or 48 h after stimulation in the non irradiated part of experiment to preserve
      the equal growth time for all samples. gamma-Irradiation of the cells abolished
      nuclear translocation of PPARgamma under its agonists treatment and preserved
      PPARgamma in the cytoplasmic pool. But it did not affect the HSP 70 expression in
      response to ciglitazone and retinoic acid. Moreover, combined gamma-irradiation
      and CI/RA treatment of the cells changed the equilibrium between Bax and Bcl-2
      mRNA to anti apoptotic state with increased expression of Bcl-2 and almost
      abolished expression of Bax. In conclusion, this paper provides an evidence for
      the anti-apoptotic action of PPARgamma agonists used along with the gamma
      radiation. Moreover, it shows that the up-regulated HSP70, in response to
      PPARgamma agonists in gamma-irradiated cultures promotes cell survival.

PMID- 18812639
TI  - Effect of carotenoids on in vitro proliferation and differentiation of oval cells
      during neoplastic and non-neoplastic liver injuries in rats.
AB  - The goal of this study was to investigate the effects of beta-carotene and
      astaxanthin (ASX) - carotenoid without provitamin A activity on the proliferation
      and differentiation of rat oval cells (OC) in vitro. Oval cells were isolated
      from two groups of animals: I - partial hepatectomised (PH) and II-
      diethylnitrosamine (DEN) treated rats. At various time points cell lysates were
      separated by PAGE. For immunodetection primary antibodies against CD-34, Ck19 and
      albumin were used. Medium concentration of fibrinogen and haptoglobin was
      measured. Mitochondrial competence of cells was expressed as the proliferation
      index. In comparison to HP- and DEN-obtained oval cells cultured without
      carotenoids, the addition of beta-carotene and ASX increased albumin expression
      during the experimental period. The same condition didn't reveal CK19 expression.
      CD34 expressed by oval cells was detected up to the 5(th) week of beta-carotene
      and ASX absence in the medium. beta-carotene addition resulted in a decrease of
      the proliferative activity of OC, with significant changes in 48 h, the 5(th) and
      15(th) week of incubation. ASX (p < or = 0.05) inhibited the proliferation,
      especially in 24h and 5(th) week of cell culture. In respect to haptoglobin
      concentration, its maximum value after the 10(th) week was observed. The
      fibrinogen level obtained from DEN-oval cells incubated with beta-carotene
      elevated from 480+/-6.87 microg/ml after 24h to 5520+/-34,56 microg/ml after the
      15(th) week. In a condition without carotenoids fibrinogen concentration did not
      exceed 2280+/-31.5 microg/ml after the 15(th) week of cell culture.

PMID- 18812640
TI  - Non-variceal upper gastrointestinal bleeding--guidelines on management.
AB  - In gastroenterology non-variceal upper gastrointestinal bleeding is health
      hazard. Frequency of occurrence accounts for 40-150 cases per 100000 inhabitants
      with death rate of 7-14%. Researches which goal is to improve treatment
      effectiveness as well as to establish standardized procedures for managing
      patients with symptoms of non-variceal upper gastrointestinal bleeding; have been
      conducted since many years. At the moment of admission, designed standards enable
      appropriate elaboration of patients' health state, referral to the right clinic
      and implementation of the most accurate treatment methods. Increase of
      suppression of primary bleeding as well as prevention of recurrence is associated
      with dynamic development of endoscopic treatment methods as well as with
      optimization of pharmacological treatment. In significant percentage, efficiency
      of non - variceal bleedings treatment depends on clinic's character (availability
      of equipment, experience of personnel) and on cooperation between several
      specialists (including gastroenterologist, surgeon, anesthetist, operative
      radiologist). Aim of the work is to present the latest evaluation of the
      mentioned subject, based on accessible literature. This work includes the basic
      principles for determination of bleeding intensity and risk of its recurrence as
      well as directions referring to fluids resuscitation and to monitoring of
      patients. Information on currently applied endoscopic methods for inhibition of
      non variceal upper gastrointestinal bleeding (injection, mechanical and thermo
      coagulation techniques), comparison of their efficiency and possibility of
      application is provided in the work. The paper work also presents the newest
      directives for pharmacological treatment and guidelines for possible surgical
      treatment.

PMID- 18812641
TI  - Pathophysiology of portal hypertension.
AB  - In last years significant progress in recognizing mechanisms of portal
      hypertension pathophysiology was done. However, some unclear topics in this
      disease still exist. Portal hypertension is primarily caused by the increase in
      resistance to portal outflow and secondly by an increase in splanchnic blood
      flow. Portal hypertension is associated with changes in the intrahepatic,
      systemic, and portosystemic collateral circulation. Alterations in vasoreactivity
      (vasodilation and vasoconstriction) play a central role in the pathophysiology of
      portal hypertension by contributing to increased intrahepatic resistance,
      hyperdynamic circulation, and expansion of the collateral circulation. Among
      vasoactive substances which are activated in portal hypertension nitric oxide
      (NO) is considered as the most important vasodilator. Endothelin-1 and
      cyclooxygenase-derived prostaglandins are the main vasoconstrictor factors. The
      imbalance between the hyperresponsiveness and overproduction of vasoconstrictors
      and the hyporesponsiveness and impaired production of vasodilators are the
      mechanisms responsible of the increased vascular one in the sinusoidal area of
      the liver. New concepts in the pathophysiology of portal hypertension find the
      significant role of hepatic stellate cells activated by endothelial factors which
      cause vascular remodeling as an adaptive response of the portal vessels wall. The
      most frequent causes of portal hypertension include portal vein thrombosis,
      storage diseases of the liver, hepatic cirrhosis (independent of etiology),
      hepatic veins thrombosis and schistosomiasis. Understanding the pathophysiology
      of portal hypertension could be of great utility in preventing and curing the
      complications of portal hypertension, such as esophageal varices, hepatic
      encephalopathy, ascites.

PMID- 18812642
TI  - RAS inhibitors decrease apoptosis of acinar cells and increase elimination of
      pancreatic stellate cells after in the course of experimental chronic
      pancreatitis induced by dibutyltin dichloride.
AB  - Chronic pancreatitis (CP) is a progressive disease, in which the exocrine
      function of the gland is gradually lost and fibrosis develops due to repeated
      episodes of acute pancreatitis. The aim of the study was to investigate the
      effects of RAS inhibitors on the apoptosis of acinar cells and pancreatic
      stellate cells (PSCs) elimination in experimental CP induced by dibutyltin
      dichloride (DBTC). CP was induced by administration of DBTC to the femoral vein.
      Simultaneously captopril, losartan, enalapril and lisinopril were administered
      intraperitoneally. The rats were decapitated after 60 days and tissue of pancreas
      was collected. In rats treated by DBTC the features of inflammatory infiltration,
      ductal lumen dilatation, fibrosis were found. Strong reactivity with caspase2(L)
      and clusterin-beta antibodies was observed in areas of fibrosis. In animals
      treated with RAS inhibitors inflammatory changes and fibrosis were less severe.
      In groups of rats treated with DBTC and RAS inhibitors immunoreactivity of
      caspase(2L) and clusterin-beta was weak. Positive immunostaining against smooth
      muscle actine and desmin was observed in the elongated cells (PSC-s). This
      reaction was weak in groups of rat treated with DBTC and RAS inhibitors.
      Treatment of CP rats with RAS inhibitors alleviate apoptosis of pancreatic acinar
      cells and induces PSCs elimination.

PMID- 18812643
TI  - Roles of short-chain fatty acids receptors, GPR41 and GPR43 on colonic functions.
AB  - Short chain fatty acids (SCFAs) are the major anions in the large intestine. They
      are produced by a bacterial fermentation of dietary fiber. SCFAs are known to
      have a variety of physiological and pathphysiological effects on intestine.
      However, the mechanisms by which intraluminal SCFAs are sensed are not known. In
      2003, two orphan G protein coupled receptors (GPRs), GPR41 and GPR43, have been
      cloned and demonstrated to be receptors for SCFAs. Thus, we had attempted to make
      antibodies raised against GPR43 and GPR41 to elucidate the roles of SCFAs on
      colonic functions. We have also evaluated the effects of SCFAs on colonic
      motility to define the physiological roles on luminal SCFAs. In rat and human
      colon, GPR43 protein was detected by Western blot analysis in extracts of whole
      wall and separated mucosa, but not in muscle plus submucosa extract. By
      immunohistochemistry, GPR43 immunoreactivity was localized with enteroendocrine
      cells expressing peptide YY, whereas 5-HT immunoreactive enteroendocrine cells
      were not immunoreactive for GPR43. GPR41 immunoreactivity was also found in human
      colon. In functional studies, propionate and butyrate concentration-dependently
      (10 microM - 10 mM) induced phasic and tonic contractions in rat colonic circular
      muscle. The propionate-induced phasic contraction was attenuated by atropine,
      tetrodotoxin and the 5-HT(4) receptor antagonists SB204070. However, acetate did
      not induce phasic or tonic contractions. Propionate-induced responses were not
      observed in mucosal free preparations. The present results suggest that the SCFA
      induced physiological effects on colonic functions might be attributable to the
      activation of SCFA receptors on epithelial cells in the colon.

PMID- 18812644
TI  - A surgical device for radiofrequency ablation of large liver tumors.
AB  - Radiofrequency ablation has become an accepted treatment option of patients with
      primary and metastatic liver tumors. We propose an ablation electrode array
      consisting of 4-8 blade shaped electrodes arranged in a circular geometry for the
      treatment of large liver tumors. We developed a 3D code based on the finite
      difference method for evaluating the effect of different numbers of electrodes
      (4, 6 and 8) and electrode distance on lesion size. The configuration with six
      electrodes can ablate a volume of 70 x 70 x 40 mm(3) in approximately 5 min, with
      tissue temperature above 50 degrees C throughout the treatment volume. We then
      performed an experimental study in polyacrylamide gel in order to validate the
      theoretical results. The average temperature error between the simulation and the
      experiment was 3.8% at the center of the electrode array. This study shows that
      the proposed device potentially allows more rapid treatment of large tumors than
      current radiofrequency ablation devices.

PMID- 18812645
TI  - Ventricular fibrillation time constant for swine.
AB  - The strength-duration curve for cardiac excitation can be modeled by a parallel
      resistor-capacitor circuit that has a time constant. Experiments on six pigs were
      performed by delivering current from the X26 Taser dart at a distance from the
      heart to cause ventricular fibrillation (VF). The X26 Taser is an electromuscular
      incapacitation device (EMD), which generates about 50 kV and delivers a pulse
      train of about 15-19 pulses s(-1) with a pulse duration of about 150 micros and
      peak current about 2 A. Similarly a continuous 60 Hz alternating current of the
      amplitude required to cause VF was delivered from the same distance. The average
      current and duration of the current pulse were estimated in both sets of
      experiments. The strength-duration equation was solved to yield an average time
      constant of 2.87 ms +/- 1.90 (SD). Results obtained may help in the development
      of safety standards for future electromuscular incapacitation devices (EMDs)
      without requiring additional animal tests.

PMID- 18812646
TI  - Studies on effective atomic number, electron density and kerma for some fatty
      acids and carbohydrates.
AB  - The effective atomic number, Z(eff), the effective electron density, N(el), and
      kerma have been calculated for some fatty acids and carbohydrates for photon
      interaction in the extended energy range from 1 keV to 100 GeV using an accurate
      database of photon-interaction cross sections and the WinXCom program. The
      significant variation of Z(eff) and N(el) is due to the variations in the
      dominance of different interaction processes in different energy regions. The
      maximum values of Z(eff) and N(el) are found in the low-energy range, where
      photoelectric absorption is the main interaction process. The minimum values of
      Z(eff) and N(el) are found at intermediate energies, typically 0.05 MeV < E < 5
      MeV, where Compton scattering is dominant. In this case, Z(eff) is equal to the
      mean atomic number of the bio-molecule. Wherever possible, the calculations are
      compared with experimental results. A comparison is also made with the single
      values of the Z(eff) and N(el) provided by the program XMuDat. It is also
      observed that carbohydrates have a larger kerma than fatty acids in the low
      energy region, where photoelectric absorption dominates. In contrast, fatty acids
      have a larger kerma than carbohydrates in the MeV range, where Compton scattering
      is the main interaction process.

PMID- 18812647
TI  - Radiotherapy in the presence of contrast agents: a general figure of merit and
      its application to gold nanoparticles.
AB  - Delivering sufficient dose to tumours while sparing surrounding tissue is one of
      the primary challenges of radiotherapy, and in common practice this is typically
      achieved by using highly penetrating MV photon beams and spatially shaping dose.
      However, there has been a recent increase in interest in the possibility of using
      contrast agents with high atomic number to enhance the dose deposited in tumours
      when used in conjunction with kV x-rays, which see a significant increase in
      absorption due to the heavy element's high-photoelectric cross-section at such
      energies. Unfortunately, the introduction of such contrast agents significantly
      complicates the comparison of different source types for treatment efficacy, as
      the dose deposited now depends very strongly on the exact composition of the
      spectrum, making traditional metrics such as beam quality less valuable. To
      address this, a 'figure of merit' is proposed, which yields a value which enables
      the direct comparison of different source types for tumours at different depths
      inside a patient. This figure of merit is evaluated for a 15 MV LINAC source and
      two 150 kVp sources (both of which make use of a tungsten target, one with
      conventional aluminium filtration, while the other uses a more aggressive thorium
      filter) through analytical methods as well as numerical models, considering
      tissue treated with a realistic concentration and uptake ratio of gold
      nanoparticle contrast agents (10 mg ml (-1) concentration in 'tumour' volume,
      10:1 uptake ratio). Finally, a test case of human neck phantom is considered with
      a similar contrast agent to compare the abstract figure to a more realistic
      treatment situation. Good agreement was found both between the different
      approaches to calculate the figure of merit, and between the figure of merit and
      the effectiveness in a more realistic patient scenario. Together, these
      observations suggest that there is the potential for contrast-enhanced
      kilovoltage radiation to be a useful therapeutic tool for a number of classes of
      tumour on dosimetric considerations alone, and they point to the need for further
      research in this area.

PMID- 18812648
TI  - Evaluation of quantitative (90)Y SPECT based on experimental phantom studies.
AB  - In SPECT imaging of pure beta emitters, such as (90)Y, the acquired spectrum is
      very complex, which increases the demands on the imaging protocol and the
      reconstruction. In this work, we have evaluated the quantitative accuracy of
      bremsstrahlung SPECT with focus on the reconstruction algorithm including model
      based attenuation, scatter and collimator-detector response (CDR) compensations.
      The scatter and CDR compensation methods require pre-calculated point-spread
      functions, which were generated with the SIMIND MC program. The SIMIND program is
      dedicated for simulation of scintillation camera imaging and only handles
      photons. The aim of this work was therefore twofold. The first aim was to
      implement simulation of bremsstrahlung imaging into the SIMIND code and to
      validate simulations against experimental measurements. The second was to
      investigate the quality of bremsstrahlung SPECT imaging and to evaluate the
      possibility of quantifying the activity in differently shaped sources. In
      addition, a feasibility test was performed on a patient that underwent treatment
      with (90)Y-Ibritumomab tiuxetan (Zevalin). The MCNPX MC program was used to
      generate bremsstrahlung photon spectra which were used as source input in the
      SIMIND program. The obtained bremsstrahlung spectra were separately validated by
      experimental measurement using a HPGe detector. Validation of the SIMIND
      generated images was done by a comparison to gamma camera measurements of a
      syringe containing (90)Y. Results showed a slight deviation between simulations
      and measurements in image regions outside the source, but the agreement was
      sufficient for the purpose of generating scatter and CDR kernels. For the
      bremsstrahlung SPECT experiment, the RSD torso phantom with (90)Y in the liver
      insert was measured with and without background activities. Projection data were
      obtained using a GE VH/Hawkeye system. Image reconstruction was performed by
      using the OSEM algorithm with and without different combinations of model-based
      attenuation, scatter and CDR compensations. The reconstructed images were then
      evaluated in terms of the accuracy of the total activity estimate in the liver
      insert. It was found that the activity in a large source such as the liver was
      estimated with a bias of around -70%, when no compensations were included in the
      reconstruction, whereas when compensations were included the bias obtained was
      between -10 and 16%. It is concluded that although the (90)Y bremsstrahlung
      spectrum is continuous with no pronounced peak and the count rate is low, it is
      possible to achieve reasonably accurate activity estimates from bremsstrahlung
      SPECT images if proper compensations are applied in the reconstruction. This
      conclusion was also confirmed by the patient study.

PMID- 18812649
TI  - Automated cardiac motion compensation in PET/CT for accurate reconstruction of
      PET myocardial perfusion images.
AB  - Error-free reconstruction of PET data with a registered CT attenuation map is
      essential for accurate quantification and interpretation of cardiac perfusion.
      Misalignment of the CT and PET data can produce an erroneous attenuation map that
      projects lung attenuation parameters onto the heart wall, thereby underestimating
      the attenuation and creating artifactual areas of hypoperfusion that can be
      misinterpreted as myocardial ischemia or infarction. The major causes of
      misregistration between CT and PET images are the respiratory motion, cardiac
      motion and gross physical motion of the patient. The misalignment artifact
      problem is overcome with automated cardiac registration software that minimizes
      the alignment error between the two modalities. Results show that the automated
      registration process works equally well for any respiratory phase in which the CT
      scan is acquired. Further evaluation of this procedure on 50 patients
      demonstrates that the automated registration software consistently aligns the two
      modalities, eliminating artifactual hypoperfusion in reconstructed PET images due
      to PET/CT misregistration. With this registration software, only one CT scan is
      required for PET/CT imaging, which reduces the radiation dose required for CT
      based attenuation correction and improves the clinical workflow for PET/CT.

PMID- 18812650
TI  - High temporal resolution and streak-free four-dimensional cone-beam computed
      tomography.
AB  - Cone-beam computed tomography (CBCT) has been clinically used to verify patient
      position and to localize the target of treatment in image-guided radiation
      therapy (IGRT). However, when the chest and the upper abdomen are scanned,
      respiratory-induced motion blurring limits the utility of CBCT. In order to
      mitigate this blurring, respiratory-gated CBCT, i.e. 4D CBCT, was introduced. In
      4D CBCT, the cone-beam projection data sets acquired during a gantry rotation are
      sorted into several respiratory phases. In these gated reconstructions, the
      number of projections for each respiratory phase is significantly reduced.
      Consequently, undersampling streaking artifacts are present in the reconstructed
      images, and the image contrast resolution is also significantly compromised. In
      this paper, we present a new method to simultaneously achieve both high temporal
      resolution ( approximately 100 ms) and streaking artifact-free image volumes in
      4D CBCT. The enabling technique is a newly proposed image reconstruction method,
      i.e. prior image constrained compressed sensing (PICCS), which enables accurate
      image reconstruction using vastly undersampled cone-beam projections and a fully
      sampled prior image. Using PICCS, a streak-free image can be reconstructed from
      10-20 cone-beam projections while the signal-to-noise ratio is determined by a
      denoising feature of the selected objective function and by the prior image,
      which is reconstructed using all of the acquired cone-beam projections. This
      feature of PICCS breaks the connection between the temporal resolution and
      streaking artifacts' level in 4D CBCT. Numerical simulations and experimental
      phantom studies have been conducted to validate the method.

PMID- 18812651
TI  - Structural characterization of the human cerebral myelin sheath by small angle x
      ray scattering.
AB  - Myelin is a multi-lamellar membrane surrounding neuronal axons and increasing
      their conduction velocity. When investigated by small-angle x-ray scattering
      (SAXS), the lamellar quasi-periodical arrangement of the myelin sheath gives rise
      to distinct peaks, which allow the determination of its molecular organization
      and the dimensions of its substructures. In this study we report on the myelin
      sheath structural determination carried out on a set of human brain tissue
      samples coming from surgical biopsies of two patients: a man around 60 and a
      woman nearly 90 years old. The samples were extracted either from white or grey
      cerebral matter and did not undergo any manipulation or chemical-physical
      treatment, which could possibly have altered their structure, except dipping them
      into a formalin solution for their conservation. Analysis of the scattered
      intensity from white matter of intact human cerebral tissue allowed the
      evaluation not only of the myelin sheath periodicity but also of its electronic
      charge density profile. In particular, the thicknesses of the cytoplasm and
      extracellular regions were established, as well as those of the hydrophilic polar
      heads and hydrophobic tails of the lipid bilayer. SAXS patterns were measured at
      several locations on each sample in order to establish the statistical variations
      of the structural parameters within a single sample and among different samples.
      This work demonstrates that a detailed structural analysis of the myelin sheath
      can also be carried out in randomly oriented samples of intact human white
      matter, which is of importance for studying the aetiology and evolution of the
      central nervous system pathologies inducing myelin degeneration.

PMID- 18812652
TI  - Replication of butterfly wing and natural lotus leaf structures by nanoimprint on
      silica sol-gel films.
AB  - An original and low cost method for the fabrication of patterned surfaces
      bioinspired from butterfly wings and lotus leaves is presented. Silica-based sol
      gel films are thermally imprinted from elastomeric molds to produce stable
      structures with superhydrophobicity values as high as 160 degrees water contact
      angle. The biomimetic surfaces are demonstrated to be tuned from superhydrophobic
      to superhydrophilic by annealing between 200 degrees C and 500 degrees C.

PMID- 18812653
TI  - Electrospun PVA/HAp nanocomposite nanofibers: biomimetics of mineralized hard
      tissues at a lower level of complexity.
AB  - Based on the biomimetic approaches the present work describes a straightforward
      technique to mimic not only the architecture (the morphology) but also the
      chemistry (the composition) of the lowest level of the hierarchical organization
      of bone. This technique uses an electrospinning (ES) process with polyvinyl
      alcohol (PVA) and hydroxyapatite (HAp) nanoparticles. To determine morphology,
      crystalline structures and thermal properties of the resulting electrospun fibers
      with the pure PVA and PVA/HAp nanocomposite (NC) before electrospinning various
      techniques were employed, including transmission electron microscopy (TEM), high
      resolution TEM (HR-TEM), scanning electron microscopy (SEM), x-ray diffraction
      (XRD), differential scanning calorimetry (DSC) and thermogravimetric analysis
      (TGA). In addition, FT-IR spectroscopy was carried out to analyze the complex
      structural changes upon undergoing electrospinning as well as interactions
      between HAp and PVA. The morphological and crystallographic investigations
      revealed that the rod-like HAp nanoparticles exhibit a nanoporous morphology and
      are embedded within the electrospun fibers. A large number of HAp nanorods are
      preferentially oriented parallel to the longitudinal direction of the electrospun
      PVA fibers, which closely resemble the naturally mineralized hard tissues of
      bones. Due to abundant OH groups present in PVA and HAp nanorods, they strongly
      interact via hydrogen bonding within the electrospun PVA/HAp NC fibers, which
      results in improved thermal properties. The unique physiochemical features of the
      electrospun PVA/HAp NC nanofibers prepared by the ES process will open up a wide
      variety of future applications related to hard tissue replacement and
      regeneration (bone and dentin), not limited to coating implants.

PMID- 18812654
TI  - [Mental status of surgical medical staff who treated or did not treat the victims
      in Wenchuan earthquake].
AB  - OBJECTIVE: To compare and analyze the mental status of medical staff between
      Orthopedics Department who treated the victims in the earthquake and other
      surgical departments who did not treat the victims in the earthquake, and to
      provide evidence for psychological prevention and intervention in the earthquake
      aids. METHODS: Cross-sectional study was used to choose staff in the Orthopedics
      Department who treated the victims and other surgical departments who did not
      treat victims in the earthquake as eligible subject with convenient sampling. The
      research tool is Symptom Checklist-90. The questionnaire was done by participants
      with the same psychological instruction. Data were analyzed by SPSS16.0. RESULTS:
      The scores in somatization, depression,anxiety and opposition, phobic anxiety in
      the orthopedic staff were significantly higher than those of the other surgical
      staff (P < 0.05). CONCLUSION: There is disorder in mental health of medical staff
      in Orthopedics Department and mental intervention is needed.

PMID- 18812655
TI  - Association of different susceptibilities to morphine with the expression of 5
      HTT and 5-HT1AR mRNA in brain regions of SD rats.
AB  - OBJECTIVE: To investigate the possible mechanism for the different CPP
      susceptibilities. METHODS: Using a conditioned place preference (CPP) model, rats
      were selected into high and low preference groups. Using in situ hybridization,
      we examined the mRNA expression of 5-hydroxytryptamine transporter (5-HTT) and 5
      hydroxytryptamine 1A receptor (5-HT1AR) in 3 crucial regions in addiction, namely
      the ventral tegmental area (VTA), the nucleus accumbens (NAc), and the medial
      prefrontal cortex (mPFC), during the dependence and withdrawal. RESULTS: During
      dependence state, the expression of 5-HTT mRNA in each of the regions in the high
      preference group was significantly lower than that of the low preference group,
      while higher expression of 5-HT1AR mRNA in each of the regions in the high
      preference group than that of the low preference group was found (P < 0.05).
      During withdrawal state, the expression of 5-HTT mRNA in each of the regions in
      high preference group was significantly higher than that of the low preference
      group, while lower expression of 5-HT1AR mRNA in each of the regions in the high
      preference group than that of the low preference group was found (P < 0.05).
      CONCLUSION: 5-HTT and 5-HT1AR may play a role in differences in susceptibility to
      morphine.

PMID- 18812656
TI  - [Dopamine D2 receptor and transportor [corrected] in the medial prefrontal contex
      of morphine-induced conditioned place preference in Sprague-Dawley rats].
AB  - OBJECTIVE: To investigate the expression of dopamine D2 receptors (D2R) and
      dopamine transportors (DAT) located in the medial prefrontal contex (mPFC) in
      high and low conditioned place preference (CPP) rats, and to unveil the possible
      mechanism leading to different CPP susceptibilities. METHODS: One hundred and
      sixty male Sprague-Dawley rats were randomly assigned into an experiment group (n
      = 130) and a control group (n = 30). The experiment group was re-classified into
      2 groups according to CPP values:high preference group (HP group) and low
      preference group (LP group). According to the execution time-points after the
      last administration, the HP and LP group was classified into a 3-hour group (3
      h), a 72-hour group (J3d), and a 14-day group (J14d), respectively. At 3 hours,
      72 hours, and 14 days after the final injection, rats were killed and cardio
      perfused, and the brains were removed and sliced up coronarily. The mRNA levels
      of D2R and DAT in mPFC were determined with in situ hybridization. RESULTS: There
      were no significant differences of pretest scores staying at the non-preference
      chamber among the groups(P = 0.470). However, the test scores of the CPP time
      stayed at pretest natural preference in the HP group were significantly higher
      than those of the LP group(P = 0.000). In 3h, J3d, and J14d groups,the
      expressions of D2R mRNA in the HP group (125.43 +/- 2.90 approximately 142.92 +/-
      3.32) were lower than those of LP group (122.25 +/- 2.20 approximately 136.67 +/
      5.39) (P = 0.000). In 3h and J3d,the expressions of DAT mRNA in the HP group
      (157.00 +/- 3.55 approximately 145.15 +/- 3.69) were significantly lower than
      those of the LP group (150.69 +/- 3.12 approximately 138.84 +/- 3.99) (P =
      0.000). In J14d, there were no differences among 3 groups in mPFC (P = 0.458).
      CONCLUSION: D2R and DAT may be correlated closely and underlie the different
      susceptibilities to morphine induced CPP.

PMID- 18812657
TI  - Effect of losartan on cyclooxygenase-2 expression in normal human mesangial cells
      and kidneys of rats with diabetic nephropathy.
AB  - OBJECTIVE: To investigate the effect of high glucose and losartan on cell
      proliferation and cyclooxygenase-2 (COX2) expression in normal human mesangial
      cells (NHMCs), and to examine the effect of losartan on COX2 and transforming
      growth factor-beta1 (TGF-beta1) expression in a model of diabetic nephropathy
      (DN). METHODS: NHMCs were cultured in vitro in high glucose media with or without
      losartan. NHMCs proliferation and COX2 expression were determined by WST-1,
      Western blot, and RT-PCR. The rat model of DN was produced by injections of
      streptozocin (STZ). After the treatment with losartan for 4 weeks, glomerular
      hypertrophy, urinary thromboxane B2 (TXB2) and 24 h urinary protein counts were
      measured, and COX2 and TGF-beta1 expressions were investigated using
      immunohistochemical techniques and RT-PCR. RESULTS: Losartan dose-dependently
      inhibited the proliferation of NHMCs in response to high glucose. Losartan also
      decreased COX2 expression in NHMCs at high or low glucose concentrations. In vivo
      experiments found kidney weight/body weight (KW/BW), urinary TXB2 and 24 h
      urinary protein counts increased significantly in the DN group. Losartan reduced
      KW/BW, urinary TXB2, and 24 h urinary protein counts and significantly suppressed
      the over-expression of COX2 and TGF-beta1. CONCLUSION: Losartan reduces COX2
      expression in NHMCs,especially at high glucose concentrations. Losartan could
      suppress the expression of COX2 and TGF-beta1 in the kidney of DN rats and
      attenuate the renal lesions caused by DN.

PMID- 18812658
TI  - [Genetic polymorphism of 15 short tandem repeats loci of Tibetan nationality and
      its affinity with other nationalities in Tibet].
AB  - OBJECTIVE: To determine the genetic diversity of short tandem repeats (STRs) loci
      (D8S1179, D21S11, D7S820, CSF1PO, D3S1358, TH01, D13S317, D16S539, D2S1338,
      D19S433, upsilonWA, TPOX, D18S51, D5S818, and FGA), and to evaluate the genetic
      structure of Tibetan nationality and its affinity with other Tibetans (Changdu
      Tibetan, Luoba ethnic group, Deng population) and other Asian populations.
      METHODS: Fifteen STRs loci were amplified simultaneously using a multiplex PCR
      typing system. Amplified STR fragments were analyzed with an ABI PRISM 3100 Avant
      DNA Analyzer. Arlequin software version 3.1 was used to obtain allele frequencies
      and polymorphism parameters. The genetic distance (D(A)), coefficient of gene
      differentiation (Gst) values, and heterozygosity (Ht) were estimated using
      DISPAN. A phylogenetic tree from the allele frequency data at 8 STRs loci and 15
      STRs loci obtained from the literature reported previously by using the D(A) and
      Neighbor-Joining (N-J) method was constructed using MEGA Version 4.0.
      Multidimensional scaling (MDS) analysis was performed using the SPSS 14.0
      software package. RESULTS: We got 132 alleles in the population studied, with the
      frequency of 0.0050-0.5990. Ht, the power of discrimination (DP) and the
      polymorphism information content (PIC) were consistent with the forensic
      application. Cluster analysis and phylogenic trees revealed that Tibetan
      nationality had estrangement genetic affinity with other Chinese nationalities
      and Asian population. CONCLUSION: The genetic information demonstrates that the
      15 chosen gene makers are highly informative loci and are suitable for population
      genetic research and forensic application.

PMID- 18812659
TI  - [Effect of valsartan on postprandial plasma inflammatory factors in patients with
      essential hypertension].
AB  - OBJECTIVE: To explore the effect of valsartan on the concentrations of plasma
      inflammatory factors after a high-fat meal in patients with essential
      hypertension in very short time. METHODS: Fifty hypertensive patients and 25
      healthy controls were studied. Patients randomly accepted lacidipine 4 mg/d
      (lacidipine group) or valsartan 80 mg/d (valsartan group) for 1 week. The
      concentrations of plasma lipid profiles, high-sensitivity C-reactive protein
      (hsCRP) and soluble P-selectin were measured in fasting state and at 4 h after a
      single high-fat meal in all subjects at baseline and in patients after 1 week.
      RESULTS: The concentrations of postprandial plasma hsCRP and soluble P-selectin
      significantly increased after a high-fat meal in patients (P < 0.05), as compared
      with those at fasting levels, but not in the controls. The postprandial plasma
      triglyceride concentrations significantly increased in the healthy controls (P <
      0.05), but were lower than those in hypertensive patients (P < 0.01).
      Postprandial change in plasma concentration of triglyceride was significantly
      correlated with those of log (hsCRP) (r = 0.344)and soluble P-selectin (r =
      0.432), respectively (n = 75, both P < 0.01). Lipids profiles did not change
      significantly after 1 week. There was no significant difference between the
      fasting and postprandial plasma concentrations of either hsCRP or soluble P
      selectin in valsartan group, while the postprandial increments of inflammatory
      factors were still significant in the lacidipine group. CONCLUSION: High-fat meal
      can induce postprandial inflammation response in patients with essential
      hypertension. Valsartan effectively attenuates this postprandial inflammation
      response within a very short time.

PMID- 18812660
TI  - [Expression of PDCD5 in multiple myeloma and its relation with BCL-2].
AB  - OBJECTIVE: To determine the expression of apoptosis related gene PDCD5 in
      multiple myeloma (MM), and to analyze the relation between PDCD5 and BCL-2.
      METHODS: The expressions of PDCD5 and BCL-2 protein and mRNA were determined by
      immunohistochemical staining method, flow cytometry (FCM) and reverse
      transcription polymerase chain reaction (RT-PCR) method in bone marrow
      mononuclear cells. We also analyzed the relation between PDCD5 and BCL-2.
      RESULTS: Immunohistochemical staining showed that PDCD5 protein positive cell
      percentage, staining intensity index (SII) of PDCD5 protein, BCL-2 protein
      positive cell percentage, and SII of BCL-2 protein were (34.75 +/- 6.49)%,
      (281.16 +/- 75.33), (29.97 +/- 5.57)%, and (224.94 +/- 57.72) in the MM group and
      (52.98 +/- 5.84)%, (462.84 +/- 39.77), (5.56 +/- 1.95)%, and (27.84 +/- 9.75) in
      the control group (all P < 0.05). Results of FCM showed that PDCD5 protein
      positive percentage and mean fluorescence intensity of PDCD5 were (78.11 +/-
      21.63)% and (61.73 +/- 11.04) in the MM group and (89.46 +/- 9.98)% and (353.04
      +/- 123.26) in the control group (all P < 0.05). RT-PCR showed that relative
      expression of PDCD5 and BCL-2 mRNA were (0.33 +/ -0.07) and (0.33 +/- 0.08) in
      the MM group and (0.53 +/- 0.05) and (0.12 +/- 0.02) in the control group (all P
      < 0.05). The positive cell percentage of PDCD5 and BCL-2 protein was negative
      correlation (r = -0.86, P < 0.05); the expression of PDCD5 and BCL-2 mRNA was the
      same status (r = -0.90, P < 0.05). CONCLUSION: The expressions of PDCD5 protein
      and mRNA in MM patients are down-regulated, but the expressions of BCL-2 protein
      and mRNA are up-regulated. The mRNA and protein expression of PDCD5 and BCL-2 has
      negative correlation.

PMID- 18812661
TI  - [Changes of color pattern reversal visual evoked potential of primary glaucoma].
AB  - OBJECTIVE: To investigate the changes of color pattern reversal visual evoked
      potential (CPR-VEP)of primary glaucoma using different temporal frequencies, and
      to search for the best temporal frequency parameters and color parameters.
      METHODS: Vision Monitor visual electrophysiograph (Metrovision, France) was used
      to record CPR-VEP at different temporal frequencies (1, 2, 4, 8, 16, and 32 Hz)
      and different color stimulations (black/white, red/green, blue/yellow) in 41
      cases (70 eyes) with primary glaucoma (glaucoma group) and 13 normal subjects (26
      eyes) (normal control group). P100 wave amplitudes were compared. RESULTS: (1) In
      the normal control group, P100 amplitudes declined while the temporal frequency
      of black/white stimulation was increasing, but they had peaks at 2 Hz and 8 Hz
      red/green stimulation and blue/yellow stimulation. (2) In the glaucoma group, CPR
      VEP P100 declined while temporal frequency was increasing under 3 color
      stimulations, but had a peak at 8 Hz. At 2 Hz-16 Hz, P100 amplitudes were related
      with the mean defect of Humphrey visual field, especially with all 3 color
      stimulations at 8 Hz and with blue/yellow stimulation at 2 Hz and 16 Hz. (3) P100
      amplitude was most different under the 3 color stimulations between the 2 groups
      at 8 Hz. CONCLUSION: The changes of CPR-VEP P(100) amplitude can objectively
      reflect the glaucoma visual function damage. CPR-VEP P100 amplitude has certain
      value in studying glaucoma under different color stimulations (black/white,
      red/green, blue/yellow) at 8 Hz, and blue/yellow stimulation at 2 Hz and 16 Hz.

PMID- 18812662
TI  - [Characteristics of ocular adnexal non-Hodgkin lymphoma].
AB  - OBJECTIVE: To investigate the clinical manifestation and pathological features of
      primary ocular adnexal non-Hodgkin lymphoma. METHODS: Data of 18 patients with
      biopsy-proven ocular adnexal non-Hodgkin lymphoma at Xiangya hospital were
      reviewed.The disease site, clinical manifestation,imaging and pathological
      features of the tumor were summarized. RESULTS: All patients had typical
      presentation of an adnexal mass.Twelve(66.7%) patients had orbital involvement,
      3(16.7%) had conjunctival, and 3(16.7%) had lymphoma involving the eyelids.Eight
      patients were misdiagnosed as "inflammatory pseudotumour" before the operation
      according to their clinical and imaging examination,another 8 patients were
      diagnosed as "ocular adnexal tumour with unknown nature" before the operation.
      According to the pathologic diagnosis, 16 patients (88.9%)had marginal zone
      lymphomas of mucosa-associated lymphoid tissue(MZL-MALT) and 2 (11.1%) had NK/T
      cell lymphoma. CONCLUSION: The typical presentation of ocular adnexal lymphoma is
      a painless mass.Orbital connective tissue is the most involved anatomical site.
      The diagnosis of ocular adnexal non-Hodgkin lymphoma is difficult which could
      easily be misdiagnosed as "inflammatory pseudotumour". MZL-MALT is the most
      common pathologic type.

PMID- 18812663
TI  - [Histopathologic and ultrastructural study of extraocular muscles in thyroid
      associated ophthalmopathy].
AB  - OBJECTIVE: To investigate histopathologic and ultrastructural changes of
      extraocular muscles (EOM) in thyroid associated ophthalmopathy (TAO). METHODS:
      Twelve EOM specimens from 11 patients with TAO were observed. Each of the
      specimen was stained with HE and observed by light microscope,and then was
      sectioned with ultrathin method and observed by transmission electronic
      microscope. RESULTS: Under the light microscope, sarcoplasm coagulation,granular
      degeneration, vacuolization and necrosis were found in the extraocular muscular
      cells.Under the electronic microscope, there were disturbance and disappearance
      of the Z line in part of muscular fibers and various degrees of sarcoplasmic
      reticulum dilatation, myofilament lysis and destruction with formation of
      vacuoles.In severe cases,the muscular cells could be completely destroyed and
      phagocytosed by macrophages,fibrosis occurred and myofibroblasts were found in
      some cases. CONCLUSION: The extraocular muscles in TAO are destroyed at various
      degrees,and the muscular cells may be the target cells in TAO.

PMID- 18812664
TI  - [The effect of losartan on glomerular sclerosis in rats with diabetic
      nephropathy].
AB  - OBJECTIVE: To explore the degradation mechanism of losartan on extracellular
      matrix in rats with diabetic nephropathy. METHODS: The rat model of diabetic
      nephropathy was established by streptozotozin(STZ) injection, and the rats were
      randomly divided into 3 groups: (a normal group, a model group and a losartan
      group). For 16 weeks, the serum creatinine and urea nitrogen were measured, and
      glomerular sclerosis index(GSI) were caculated. The expression of collagen Type
      IV,connective tissue growth factor and transforming growth factor-beta1 were
      examined by Western blot and real time-PCR respectively. RESULTS: Blood urea
      nitrogen, GSI and the expressions of collagen Type IV and CTGF protein in the
      losartan group were lower than those in the model group(all P<0.05), and the
      expressions of collagen Type IV mRNA,TGF-beta1 mRNA and CTGF mRNA were lower than
      those in the model group (all P<0.05). CONCLUSION: Losartan modulates glomerular
      sclerosis and decreases the accumulation of collagen Type IV by inhibiting TGF
      beta1 and CTGF.

PMID- 18812665
TI  - [Effect of enalapil on renal interstitial fibrosis in rats with unilateral
      ureteral obstruction].
AB  - OBJECTIVE: To investigate the effect of enalapril on renal interstitial fibrosis
      in rats with unilateral ureteral obstruction(UUO). METHODS: UUO model was induced
      by ligating the left ureter in rats. Male Sprague-Dawley(SD) rats were randomly
      divided into a sham-operated group(n=16), a UUO model group(n=24), and an
      enalapril treated group(n=24). The rats were treated with 10 mg/kg.d by gastric
      gavage in the enalapril treated group from 24 h before the operation, and the
      rats were treated with the identical dose of normal saline in the other 2 groups.
      The rats were sacrificed at 3,7,14, and 21 days after UUO. Pathological changes
      of the renal tissue were observed by HE and Masson staining, the mRNA expression
      of collagen I (Col I) was detected by real-time PCR, and the protein expression
      of connective tissue growth factor (CTGF) was detected by Western blot. RESULTS:
      The renal interstitial damage index, relative collagen area and the expression of
      Col I mRNA and CTGF in the renal tissues in the model group increased with the
      prolongation of obstruction. Enalapril significantly reduced the renal
      interstitial damage index and relative collagen area, and inhibted the expression
      of Col I mRNA and CTGF. There was significant difference on day 3,7,and 14
      (P<0.05), but not on day 21 (P>0.05). CONCLUSION: Enalapril significantly
      attenuates renal interstitial fibrosis by supressing the expression of Col I mRNA
      and CTGF.

PMID- 18812666
TI  - [Design and manufacture of the static 3 dimensional screw-plate system and its
      matching tools].
AB  - OBJECTIVE: To design and manufacture a new type instrument and its matching tools
      for the proximal femur. METHODS: A new type instrument of subtrochanterical
      fracture-static 3-dimensional screw-plate system(STDSP)was designed and
      manufactured. The different types of accessory instruments which adapted to
      STDSP,the aiming guide, and the accessory tools were also designed and
      manufactured, and they were tested on bones. RESULTS: STDSP included 3 special
      lag screws and 1 anatomic plate. The lag screws distributed in femoral neck like
      "or"shape. There was 135 degree between the lag screws and femoral shaft. The
      shape of the plate was similar to the anatomic structure of the proximal
      thighbone. The posterior screw was stably connected to the plate. The plate was
      affixed crosswise to the lateral and anterior side by bicortical screws. The
      aiming guides and all kinds of accessory tools could help to install STDSP
      exactly and conveniently,which was verified on cadavers and X-ray photographs.
      CONCLUSION: STDSP has the function of dynamic compressing in 3-dimensional space,
      and can match with the structure of the proximal femur preferably. STDSP may be a
      suitable instrument to the subtrochanteric fractures. The accessory apparatus of
      STDSP has simple configuration,and can let the STDSP be installed accurately,
      conveniently and rapidly.

PMID- 18812667
TI  - [Effect of content of hepatitis B virus DNA in the serum on the pathologic change
      in hepatitis B virus associated-glomerulonephritis].
AB  - OBJECTIVE: To investigate the correlation between the content of hepatitis B
      virus DNA(HBV-DNA) in the serum and the pathologic change in hepatitis B virus
      associated-glomerulonephritis (HBV-GN). METHODS: Forty one HBV-GN patients were
      divided into 3 groups by the content of HBV-DNA in the serum:low replicate
      group,midrange replicate group, and high replicate group. The relationship with
      the content of HBV-DNA in the serum and pathologic stage or change was analyzed
      in 35 membranous glomerulopathy patients; Effect of the content of hepatitis B
      virus DNA in the serum on HBVAg deposition in glomeruli of kidney was examined by
      immunohistochemistry; Effect of HBVAg deposition on pathologic change was
      observed in membranous glomerulopathy patients. RESULTS: With the multiplication
      of HBV-DNA in the serum, the pathologic lesion was aggravating from Stage I to
      Stage III in membranous glomerulopathy patients; the deposition of HBVAg in
      glomeruli of kidney was increasing; with the increasing of deposition of HBVAg in
      glomeruli of kidney, the pathologic lesion was aggravating in membranous
      glomerulopathy patients. CONCLUSION: With the multiplication of HBV-DNA in the
      serum, the deposition of HBVAg in glomeruli of kidney increases, and the
      pathologic lesion aggravates, which have significant correlation.

PMID- 18812668
TI  - [Clinical diagnosis of breast cancer with nonpalpable tumor].
AB  - OBJECTIVE: To investigate the early diagnosis of breast cancer with nonpalpable
      tumor. METHODS: Forty-six cases of clinical nonpalpable tumor were examined by
      mammography and sonography.The cases of nipple discharge were also examined by
      fiberoptic ductoscopy. RESULTS: Breast cancer in 46 cases was diagnosed by
      pathological examination. Of them, 34 diagnosed with breast cancer were found
      with nodus, calcification or confused structure, and so on, 5 were considered
      benign tumor, and 7 were not found lesion by mammography. Thirty-one cases were
      diagnosed with breast cancer, 6 with benign tumor, and 9 were not found occupying
      lesion by sonography. Occupying lesions were found in 6 cases of nipple discharge
      by fiberoptic ductoscopy and were finally diagnosed by biopsy. CONCLUSION:
      Mammography and sonography are important methods in early discovering breast
      cancer. Early diagnosis rate of breast cancer can be elevated by signs of early
      breast cancer and combined examination of mammograply and sonography.

PMID- 18812669
TI  - [One stage posterior vertebral column resection for the treatment of
      thorciclumbar tuberculosis with kyphotic deformity].
AB  - OBJECTIVE: To evaluate the clinical outcome of one stage posterior vertebral
      column resection in patients with spinal tuberculosis combined with kyphotic
      deformity. METHODS: Thirty-six patients with spinal tuberculosis combined with
      kyphotic deformity underwent posterior one-stage vertebral column resection
      reducing tension on the spinal cord from 1998 to 2006. The patients were
      mobilized with a thoracolumbar orthosis for 3 months. All patients had a minimum
      of a 2-year follow-up, and clinical examinations and radiographs were obtained at
      6-month intervals. RESULTS: No perioperative mortality occurred. The average
      duration of surgery was 208 (145 approximately 385) min. The kyphotic Cobb angle
      improved from the preoperative average of 57.2 degree(17 degree approximately 86
      degree) to a postoperative average of 8.9 degree(-6 degree approximately 27
      degree). The average horizontal distance between C(7) and S(1) was 13.6 (8
      approximately 19) mm preoperatively and 3.6 (-11 approximately 9) mm
      postoperatively. Nineteen patients had preoperative neurological deficits. Of
      them, 89.5% (17/19) showed a postoperative neurologic improvement. Perioperative
      complications occurred in 3(8.5%) of the 36 patients with pneumonias and
      superficial infections. Twenty-five patients (69.4%) showed radiographic evidence
      of solid fusion in the follow-up examinations. In the follow-up, 25% (9/36)
      patients rated their results as excellent, 66.7% (24/36) as good, 2 as fair, and
      1 as poor. CONCLUSION: One stage posterior vertebral column resection for the
      treatment of spinal tuberculosis with kyphotic deformity is safe and effective.
      Because this procedure is highly technical, the surgeon must be familiar with the
      pathoanatomy and the operation must be carefully done.

PMID- 18812670
TI  - [Clinical efficacy of irbesartan and amiodarone in elderly patients with
      paroxysmal atrial fibrillation].
AB  - OBJECTIVE: To investigate the effect of combination of irbesartan and amiodarone
      in elderly patients with paroxysmal atrial fibrillation. METHODS: Ninety-one
      patients with paroxysmal atrial fibrillation were randomly divided into 2 groups:
      Group I (amiodarone group, n=45) and Group II (amiodarone plus Irbesartan group,
      n=46).After 18 month follow-up, the maintenance rate of sinus rhythm was measured
      in the 3rd, 6th, 9th, 12th, and 18th months, and the left atrial diameter (LAD)
      was measured before the treatment and 6th, 12th, and 18th months after the
      treatment. RESULTS: There was no difference in the maintenance rate of sinus
      rhythm between Group I and Group II in the 3rd month. The maintenance rate of
      sinus rhythm in Group I was 72.1%, 65.1%, 60.5%, and 55.8% in the 6th, 9th, 12th,
      and 18th months, and the rate in the Group II was 88.6%, 86.4%, 81.8%, and 79.5%.
      They both had significant difference (P<0.05). At 12 months after the treatment,
      LAD in Group I was significantly larger than that of Group II (P<0.05).
      CONCLUSION: The combination of irbesartan and amiodarone is more effective than
      amiodarone alone for sinus rhythm maintenance, and may restrain the enlargement
      of the left atrium.

PMID- 18812671
TI  - [Main sources of dietary calcium in perimenopausal women in Changsha].
AB  - OBJECTIVE: To describe and analyze the main food sources of dietary calcium
      intake in perimenopausal women in Changsha,China. METHODS: Twenty-four hour
      recall method was used for 3 consecutive days to collect food intake information.
      Total calcium intake and proportion of each food were calculated. RESULTS: The
      average calcium intake was (506.61+/-33.94)mg,and calcium intake in only 6.25%
      women reach standard. The main sources of dietary calcium were vegetable, milk,
      wheat, meat, and fruits. Thirty-three kinds of food, including 15 vegetables, 3
      bean and its products, 4 kinds of milk, 5 kinds of wheat, 3 kinds of eggs, 1 kind
      of oil and 1 kind of fruit supplied about 90% of the dietary calcium. CONCLUSION:
      The average calcium intake is low in perimenopausal women in Changsha. To improve
      the situation, we should increase intake of milk, bean, and its products, with
      calcium supplementation among these people.

PMID- 18812672
TI  - [Multiple hemangioma in the gastrointestinal tract, esophagus, retroperitoneum,
      celiac trunk and neck: a case report].

PMID- 18812673
TI  - Assessing culprit lesions and active complex lesions in patients with early acute
      myocardial infarction by multidetector computed tomography.
AB  - BACKGROUND: Accurate, non-invasive characterization of culprit lesions in
      patients after acute myocardial infarction (AMI) remains challenging. In this
      prospective study, multidetector row computed tomography (MDCT) is used to assess
      culprit and active complex lesions in patients early after AMI. METHODS AND
      RESULTS: We enrolled 103 patients with first non ST-elevation AMI who underwent
      64-slices MDCT and conventional coronary angiography (CCAG). The definition of
      culprit lesion, stable non-culprit lesions and non-culprit active complex lesions
      was based on the findings of CCAG. The lesions were analyzed with MDCT data. In
      culprit lesions (n=103), luminal artery stenosis, remodeling index, plaque area
      and burden were significantly higher than non-culprit lesions (n=129).
      Multivariate discriminant analysis showed that MDCT density could discriminate
      culprit from non-culprit lesions. Receiver-operator characteristic curve analysis
      identified the optimal cutoff value of lesion density for discrimination between
      culprit and non-culprit lesion as 49.6 Hounsfield units (HU); this value was
      associated with a sensitivity, specificity and accuracy of 88.4%, 87.4%, and
      87.9%, respectively. The MDCT in the stable non-culprit lesions (81.8+/-15.5 HU)
      was significantly higher than that in culprit lesions or non-culprit active
      complex lesions (33.2+/-13.8 and 48.3+/-15.7 HU, p<0.001). CONCLUSIONS: MDCT can
      predict culprit lesions in patients early after AMI, and identify multiple
      complex lesions.

PMID- 18812674
TI  - Serum N-3 polyunsaturated fatty acid levels correlate with the extent of coronary
      plaques and calcifications in patients with acute myocardial infarction.
AB  - BACKGROUND: The relationship between serum fatty acid levels and the extent of
      coronary plaques and calcification was examined in patients with acute myocardial
      infarction (AMI). METHODS AND RESULTS: The serum levels of the n-3
      polyunsaturated fatty acids (eicosapentaenoic acid (EPA) and docosahexaenoic acid
      (DHA)) and the n-6 polyunsaturated fatty acids (arachidonic acid (AA) and dihomo
      gamma-linolenic acid (DGLA)) were determined using gas chromatography on
      admission of 95 consecutive patients with their first AMI and 17 controls. Using
      multidetector-row computed tomography, soft plaques and calcification lesions
      were scored according to the extent of coronary involvement. Serum logarithmic
      transformed (log) EPA and logDHA levels were inversely correlated with soft
      plaque scores (r=-0.546, p<0.0001 and r=-0.377, p<0.0001, respectively). Serum
      logAA and logDGLA levels were not significantly correlated with soft plaque
      scores. Serum logEPA and logDHA levels were significantly, but weakly, correlated
      with calcification scores. Multivariate analysis with clinical characteristics
      and risk factors selected serum n-3 polyunsaturated fatty acid levels as
      independent factors associated with the extent of coronary soft plaques.
      CONCLUSION: The present study demonstrates a significant correlation between
      serum n-3 polyunsaturated fatty acid levels and the extent of coronary soft
      plaques and calcification in AMI patients.

PMID- 18812675
TI  - Application of support vector machine classifiers to preoperative risk
      stratification with myocardial perfusion scintigraphy.
AB  - BACKGROUND: Myocardial perfusion single-photon emission computed tomography
      (SPECT) has been used for risk stratification before non-cardiac surgery.
      However, few authors have used mathematical models for evaluating the likelihood
      of perioperative cardiac events. METHODS AND RESULTS: This retrospective cohort
      study collected data of 1,351 patients referred for SPECT before non-cardiac
      surgery. We generated binary classifiers using support vector machine (SVM) and
      conventional linear models for predicting perioperative cardiac events. We used
      clinical and surgical risk, and SPECT findings as input data, and the occurrence
      of all and hard cardiac events as output data. The area under the receiver
      operating characteristic curve (AUC) was calculated for assessing the prediction
      accuracy. The AUC values were 0.884 and 0.748 in the SVM and linear models,
      respectively in predicting all cardiac events with clinical and surgical risk,
      and SPECT variables. The values were 0.861 (SVM) and 0.677 (linear) when not
      using SPECT data as input. In hard events, the AUC values were 0.892 (SVM) and
      0.864 (linear) with SPECT, and 0.867 (SVM) and 0.768 (linear) without SPECT.
      CONCLUSION: The SVM was superior to the linear model in risk stratification. We
      also found an incremental prognostic value of SPECT results over information
      about clinical and surgical risk.

PMID- 18812676
TI  - Adipokines and the prediction of the accumulation of cardiovascular risk factors
      or the presence of metabolic syndrome in elementary school children.
AB  - BACKGROUND: Information is limited about how adipokines predict the accumulation
      of cardiovascular (CV) risk factors or the presence of metabolic syndrome (MS) in
      children. METHODS AND RESULTS: The subjects were 321 children (200 boys and 121
      girls; 109 normal and 212 obese) aged 6-12 years. Obesity was defined as a body
      mass index of >or= the 95(th) percentile for age and sex. MS was defined by using
      the newly established Task Force criteria. The levels of the adipokines-
      adiponectin, leptin, ghrelin, high sensitive C-reactive protein (CRP) and
      resistin--were measured. Regression analyses revealed that high leptin levels
      were predictive of the accumulation of CV risk factors in normal weight, obese,
      and entire (normal weight and obese) group of subjects. High CRP in the normal
      weight group and low adiponectin in the obese and the entire groups were also
      independently predictive of the accumulation of risk factors. A high leptin level
      was solely predictive of the presence of MS in obese and entire groups.
      CONCLUSIONS: Leptin was the most sensitive marker for predicting the accumulation
      of CV risk factors and the presence of MS in elementary school children. Primary
      prevention is important because both leptin and adiponectin levels abruptly
      worsened when children obtained any 1 risk factor.

PMID- 18812677
TI  - Effects of carperitide on the long-term prognosis of patients with acute
      decompensated chronic heart failure: the PROTECT multicenter randomized
      controlled study.
AB  - BACKGROUND: Carperitide is used to treat acute decompensated heart failure
      (ADHF), but its effects on long-term prognosis have not been studied. METHODS AND
      RESULTS: A multicenter randomized controlled study of 49 patients with ADHF was
      performed to clarify the drug's effects on long-term prognosis. Low-dose
      carperitide (0.01-0.05 microg x kg(-1 ) x min(-1)) was infused for 72 h as the
      initial treatment (n=26), whereas in the control group (n=23), standard medical
      treatment other than carperitide was given without limitation. Anti-aldosterone
      drugs were prohibited in both groups. During carperitide infusion, significant
      increases of the atrial natriuretic peptide and cyclic GMP levels and a
      significant decrease in the heart-type fatty acid-binding protein/serum
      creatinine ratio were observed, suggesting inhibition of myocyte cell membrane
      damage. On the other hand, no significant differences in the plasma brain
      natriuretic peptide, troponin T, and creatinine levels were noted in either
      group. During 18-month follow-up, significant reductions of death and
      rehospitalization occurred in the carperitide vs control group (11.5% vs 34.8%;
      p=0.0359). Cox regression analysis revealed that randomization to carperitide
      (p=0.020), pretreatment systolic blood pressure >or=140 mmHg (p=0.043), and beta
      blocker therapy (p=0.016) were independent predictors for freedom from cardiac
      events. CONCLUSIONS: Acute-phase low-dose carperitide infusion improved the long
      term prognosis of patients with ADHF.

PMID- 18812678
TI  - Surgical treatment of cervical spondylosis in the elderly: surgical outcomes,
      risk factors, and complications.
AB  - The incidence of cervical spondylosis in the elderly is increasing with the
      higher proportion of elderly individuals among the Japanese population. The
      present study retrospectively analyzed the clinical and radiological features of
      this clinical entity in 107 patients with cervical spondylosis aged 70 years or
      older surgically treated between 1995 and 2005. The patients were divided into
      Group 1 (n = 60) aged between 70 and 74 years, and Group 2 (n = 47) 75 years or
      older. Patients with localized compression within 2 levels responsible for the
      neurological symptoms underwent anterior fusion, and patients with a narrow
      spinal canal were treated by laminoplasty. The pre- and postoperative
      neurological status (Neurosurgical Cervical Spine Scale) and postoperative
      complications were compared. More patients in Group 2 required laminoplasty but
      most patients underwent single-level anterior fusion. There was no statistically
      significant difference in the surgical results. Group 2 had a much higher ratio
      of anterior fusion at the C3-4 level. Many of the aged patients had multiple risk
      factors. Surgical decompression for cervical spondylosis is beneficial even in
      elderly patients. Single-level anterior fusion to treat the lesion most
      responsible for the symptoms is the least invasive choice. Elderly patients tend
      to present with multiple risk factors so require careful perioperative
      management.

PMID- 18812679
TI  - Learning curve for percutaneous endoscopic lumbar discectomy.
AB  - Percutaneous endoscopic lumbar discectomy (PELD) is one of the surgical options
      for soft lumbar disk herniation, but the learning curve is perceived to be steep.
      The first 51 PELD cases performed for single-level intracanalicular lumbar disk
      herniation causing radiculopathy by the same surgeon were prospectively studied.
      The patients were divided into 3 groups of 17 patients, and the PELD learning
      curve was assessed by evaluating operating time, failure rate, complication rate,
      and 1-year reherniation rate. One-year clinical success rate was assessed by
      telephone interviews. The herniated disk was successfully removed by PELD in 47
      patients. Four patients required subsequent open discectomy due to PELD failure.
      There were 2 minor complications. One year after surgery, clinical success was
      achieved in 42 of the 47 patients in whom PELD was initially successful, and
      reherniation developed in 5 patients. A significant reduction in operating time
      was observed after 17 patients had been treated (p = 0.0004). No significant
      differences were observed in terms of either failure rate or complication rate
      between the 3 groups. No significant differences were observed in terms of either
      the clinical success rate or the reherniation rate at 1 year after surgery. The
      PELD learning curve seems to be stable and acceptable with proper pre-PELD
      training.

PMID- 18812680
TI  - Dramatic disappearance of moyamoya disease-induced chorea after indirect bypass
      surgery.
AB  - A 31-year-old woman with moyamoya disease presented with choreiform movements
      persisting for 4.5 years. Magnetic resonance imaging showed a fine vascular
      plexus in the base of the brain but no parenchymal brain damage. Cerebral
      angiography revealed intracranial vascular abnormalities compatible with moyamoya
      disease. Single photon emission computed tomography with N-isopropyl-p-(123)I
      iodoamphetamine showed definite reduction of the regional cerebral blood flow
      (rCBF) in the bilateral striata and frontotemporoparietal cortex. rCBF study with
      acetazolamide administration indicated marked decrease of rCBF reserve in those
      regions. She underwent indirect bypass surgery (encephalo-duro-arterio-myo
      synangiosis) under a diagnosis of moyamoya disease. The choreic involuntary
      movements disappeared shortly after surgery. Postoperative angiography showed
      neovascularization in the extracranial to intracranial direction, associated with
      dramatic increase in rCBF in the involved regions.

PMID- 18812681
TI  - Gradual deterioration of brainstem cavernous angioma associated with hemophilia-
      case report.
AB  - A 49-year-old man presented with a brainstem cavernous angioma associated with
      hemophilia manifesting as gradual progression of neurological deficits over a
      period of 2 weeks. Computed tomography revealed a hematoma and perifocal edema on
      the left side of the pons, and T(2)-weighted magnetic resonance imaging revealed
      a hemosiderin rim around the lesion with venous malformation. The neurological
      deficits deteriorated despite conservative treatment, so surgery was performed 2
      weeks after admission, after supplementary therapy of factor IX. The hematoma and
      anomalous vascular component were entirely removed without intractable bleeding.
      The postoperative course was uneventful and his neurological symptoms improved.
      The histological diagnosis was cavernous angioma. Six months after onset, he was
      doing well. Surgery can be effective for the treatment of hemorrhagic cavernous
      angioma associated with hemophilia after initiation of supplementary therapy with
      coagulation factor.

PMID- 18812682
TI  - De novo formation of cavernoma after radiosurgery for adult cerebral
      arteriovenous malformation--case report.
AB  - A 47-year-old male underwent stereotactic radiosurgery (25 Gy) for a cerebral
      arteriovenous malformation located in the right caudate nucleus, using a linear
      accelerator. Complete obliteration of nidus was confirmed 20 months after
      radiosurgery. However, a hypointense mass on T(2)-weighted magnetic resonance
      imaging developed in the area adjacent to the nidus after approximately 80
      months. The mass gradually increased in size and induced severe perifocal edema
      over 2 years. The mass was successfully excised. Histological examination
      revealed that the mass consisted of dilated sinusoid vessels attached to the
      hematoma capsule, and the hematoma included clots in various stages of
      organization encapsulated by dense collagenous tissue. The histological diagnosis
      was cavernoma. De novo formation of cavernoma is well known to occur after
      radiation surgery for intracranial tumor, especially in pediatric patients, but
      is rare in adults. Based on the radiological and histological findings in the
      present case, the radiation-induced cavernoma underwent repeated bleedings
      resulting in chronic encapsulated expanding hematoma.

PMID- 18812683
TI  - Craniocervical paraganglioma with numerous pulmonary metastases--case report.
AB  - A 28-year-old man presented with a rare craniocervical paraganglioma with
      multiple pulmonary metastases manifesting as hearing disturbance, hoarseness, and
      dysphagia in February 2003. Magnetic resonance imaging depicted a large jugular
      foramen tumor extending to the deep cervical region. Chest computed tomography
      revealed numerous small pulmonary nodules. The jugular tumor was totally resected
      immediately after preoperative embolization. Histological examination revealed
      paraganglioma. Localized irradiation (54 Gy) and two courses of combination
      chemotherapy consisting of paclitaxel (80 mg/m(2)) and gemcitabine (1000 mg/m(2))
      were given. The patient remained well during follow up for 48 months and the
      number of pulmonary metastases did not increase. Local control of primary
      craniocervical paraganglioma by palliative surgical resection may be effective
      for control of metastatic lesions.

PMID- 18812684
TI  - Asymptomatic huge congenital arachnoid cyst successfully treated by endoscopic
      surgery--case report.
AB  - A female neonate was the first child of a 30-year-old mother, with unremarkable
      medical history. Prenatal ultrasonography performed at 36 weeks of gestation
      suggested intracranial mass lesion. The baby was delivered by cesarean section at
      41 weeks of gestation because of bradycardia and asphyxia. The birth weight,
      height, and head circumference were within the normal ranges with soft fontanels.
      Congenital anomaly was not observed with normal neurological findings. She was
      referred to our department at age 5 months. Physical examination revealed normal
      developmental milestones and intact endocrinological function without
      macrocephaly. Cerebral magnetic resonance (MR) imaging revealed a unilocular huge
      cyst appearing as homogeneously hypointense on T(1)- and hyperintense on T(2)
      weighted images, and extending into the basal, suprasellar, ambient,
      quadrigeminal, interpeduncular, prepontine, right cerebellopontine angle, and
      premedullary cisterns. The pituitary stalk was markedly stretched and displaced
      ventrally, and the brainstem was displaced dorsally by the cyst. No other brain
      anomalies, dysgenesis of the corpus callosum, or ventriculomegaly were
      recognized. Neuroendoscopic cystocisternostomy was performed to form a
      communication between the cyst cavity and premedullary cistern. Pressurized
      watery fluid was released on puncturing the cyst wall which consisted of
      transparent membrane. Surveillance MR imaging at 2 and 9 months after the surgery
      revealed remarkable regression without regrowth of the cyst. She remained in good
      condition and showed normal development during the follow up for 1 year 9 months.
      Less invasive prophylactic surgery using the neuroendoscope may be beneficial for
      carefully selected cases of asymptomatic neonatal arachnoid cysts.

PMID- 18812685
TI  - Cervical perimedullary arteriovenous fistula in an infant presenting with
      subarachnoid hemorrhage--case report.
AB  - A 9-month-old boy was transferred to our institute after suffering sudden seizure
      and loss of consciousness followed by cardiopulmonary arrest. Neurological
      examination on admission revealed deep coma and tetraparesis. Brain computed
      tomography revealed diffuse intracranial subarachnoid hemorrhage (SAH), whereas
      brain magnetic resonance (MR) angiography showed no intracranial abnormalities.
      MR imaging of the spine demonstrated a remarkable flow void extending from C3 to
      T1. Digital subtraction angiography revealed a perimedullary arteriovenous
      fistula (AVF) fed by the left thyrocervical trunk, associated with a varix and a
      dilated perimedullary vein. He had hypoxic encephalopathy due to transient
      cardiopulmonary arrest, and remained in the intensive care unit for 2 months.
      Thereafter, he was transferred to the pediatric ward, where his general condition
      improved, and after 7 months underwent embolization of the AVF to prevent further
      SAH. The perimedullary AVF was successfully interrupted by transarterial
      embolization with n-butyl-2-cyanoacrylate and platinum coils, and no additional
      neurological deficits developed. Post-embolization MR imaging showed loss of the
      flow void. The favorable outcome demonstrates the importance of spinal cord
      imaging in infants with SAH without other intracranial abnormalities to detect
      the presence of perimedullary AVF. Perimedullary AVFs in children are often
      associated with huge fistulas and varices, so are good candidates for
      endovascular surgery.

PMID- 18812686
TI  - Thoracic disk herniation with hematoma--case report.
AB  - A 54-year-old man presented with an extremely rare case of intervertebral disk
      herniation with hematoma in the thoracic spine, manifesting as acute progressive
      numbness and muscle weakness in the bilateral lower extremities. He had been
      treated with anticoagulants. Magnetic resonance imaging of the thoracic spine
      showed intervertebral disk herniation and severe compression of the spinal cord
      at T9-10, appearing as hyperintense on T(1)- and hypointense on T(2)-weighted
      imaging suggestive of concomitant hematoma. His symptoms completely resolved
      after resection of the brownish herniated disk material. Old hemorrhage was also
      aspirated from the intervertebral disk space. Hemosiderin deposition was found in
      the cartilaginous tissue of the resected disk. Intervertebral disk herniation
      with hematoma is extremely rare, but may occur in patients with bleeding
      diathesis.

PMID- 18812687
TI  - Fusion of magnetic resonance angiography and magnetic resonance imaging for
      surgical planning for meningioma--technical note.
AB  - A fusion technique for magnetic resonance (MR) angiography and MR imaging was
      developed to help assess the peritumoral angioarchitecture during surgical
      planning for meningioma. Three-dimensional time-of-flight (3D-TOF) and 3D-spoiled
      gradient recalled (SPGR) datasets were obtained from 10 patients with
      intracranial meningioma, and fused using newly developed volume registration and
      visualization software. Maximum intensity projection (MIP) images from 3D-TOF MR
      angiography and axial SPGR MR imaging were displayed at the same time on the
      monitor. Selecting a vessel on the real-time MIP image indicated the
      corresponding points on the axial image automatically. Fusion images showed
      displacement of the anterior cerebral or middle cerebral artery in 7 patients and
      encasement of the anterior cerebral arteries in 1 patient, with no relationship
      between the main arterial trunk and tumor in 2 patients. Fusion of MR angiography
      and MR imaging can clarify relationships between the intracranial vasculature and
      meningioma, and may be helpful for surgical planning for meningioma.

PMID- 18812688
TI  - I stand with humility.

PMID- 18812689
TI  - MDR1 single nucleotide polymorphism G2677T/A and haplotype are correlated with
      response to docetaxel-cisplatin chemotherapy in patients with non-small-cell lung
      cancer.
AB  - BACKGROUND: The multidrug resistance gene 1 (MDR1) encodes P-glycoprotein (P-gp),
      which plays an important role in mediating multidrug resistance to
      chemotherapeutic agents. MDR1 gene polymorphisms may have an impact on the
      expression and function of P-gp, thereby influencing the response to
      chemotherapy. OBJECTIVES: To investigate whether the MDR1 2677 and 3435 genotypes
      are associated with the sensitivity of non-small-cell lung cancer (NSCLC) to
      docetaxel. METHODS: In this study we investigated the potential association of
      MDR1 2677G>T at exon 21, 3435C>T at exon 26 and their haplotypes with
      chemotherapy response of 54 Han Chinese patients with NSCLC. The patients were
      treated with docetaxel-cisplatin. RESULTS: The 2677 GG genotype was associated
      with a significantly better response to chemotherapy compared with the combined
      2677 GT and TT genotype (p = 0.035). The 3435 CC genotype was also associated
      with a better response to chemotherapy compared with the combined 3435 CT and TT
      genotypes although the difference was not statistically significant (p = 0.123).
      Moreover, patients harboring the 2677G-3435C haplotype had a statistically
      significant better response to chemotherapy compared with those with the other
      haplotypes combined (p = 0.015). CONCLUSION: Our findings suggest that the MDR1
      2677G>T/A polymorphism and the 2677G-3435C haplotype are predictors of treatment
      response to docetaxel-cisplatin chemotherapy in NSCLC patients.

PMID- 18812690
TI  - Endobronchial metastases from colorectal cancers: natural history and role of
      interventional bronchoscopy.
AB  - BACKGROUND: Endobronchial metastases are rare. The most frequent primary tumors
      associated with endobronchial involvement are breast, colon and renal cell
      carcinomas. Metastases from colorectal cancers can be treated either surgically
      or with chemotherapy in order to improve survival. OBJECTIVES: This paper aims to
      report the potential role of interventional bronchoscopy in patients with
      endobronchial metastases from colorectal cancer. METHODS: This retrospective
      study included 24 patients who underwent an interventional bronchoscopy procedure
      between 1988 and 2006. All patients had verified tracheobronchial metastases and
      were treated to relieve their obstruction. Assessment of the natural history of
      metastatic colorectal carcinoma, therapeutic options and survival associated with
      endobronchial metastases are reported. RESULTS: Endobronchial metastases occurred
      at a median of 53 months (range 18-144) following the diagnosis of the primary
      tumor. Fifty-seven percent of patients had other proven metastases when the
      endobronchial involvement was diagnosed. All patients had known synchronous
      pulmonary metastases upon the discovery of tracheobronchial secondary lesions.
      The most frequently observed symptoms were dyspnea, cough and hemoptysis.
      Atelectasis was a common radiological finding. In 67% of patients, an
      interventional bronchoscopy was possible with the primary intent of relieving the
      obstruction. An endoscopic intervention provided symptomatic relief and an
      improvement in forced expiratory volume in 1 s. The median overall survival was
      70 months (range 23-245) and 14 months once the endobronchial metastase(s) had
      been diagnosed. CONCLUSION: Endobronchial metastases occur relatively late in
      patients with a metastatic colorectal neoplasm. Palliative treatment with
      interventional bronchoscopy to prevent asphyxia is a safe and effective method
      that may improve the quality of life in these patients.

PMID- 18812691
TI  - Impact of nasal continuous positive airway pressure therapy on markers of
      platelet activation in patients with obstructive sleep apnea.
AB  - BACKGROUND: Considerable evidence implicates CD40 signaling in the pathogenesis
      of atheromas. Exposure to CD40 ligand induces platelet-leukocyte conjugation, a
      heightened expression of inflammatory cytokines, matrix-degrading enzymes, and
      procoagulant factors. OBJECTIVES: To investigate the association between plasma
      soluble CD40 ligand (sCD40L) and platelet-monocyte aggregates in patients with
      obstructive sleep apnea (OSA) and to determine whether treatment of OSA with
      nasal continuous positive airway pressure (nCPAP) alters this relationship.
      METHODS: Twelve patients with OSA who were free of other diseases and 12 healthy
      controls matched for age, gender, and body mass index had blood drawn for sCD40L
      and platelet-monocyte aggregate measurements. A repeat assessment was obtained
      following 8 weeks of nCPAP therapy. RESULTS: Subjects with OSA had significantly
      higher plasma sCD40L levels and exhibited elevated platelet-monocyte aggregates
      compared to nonapneic subjects (7.6 +/- 4.3 versus 1.7 +/- 1.1, p = 0.004; and
      41.3 +/- 23.7 versus 6.7 +/- 4.9, p = 0.001, respectively). Both parameters
      correlated positively with the percentage of time spent with SpO(2) <90% (r =
      0.69, p = 0.01 and r = 0.6, p = 0.03, respectively). After 8 weeks of nCPAP
      treatment, sCD40 levels declined by 47% (p = 0.003) and platelet-monocyte
      aggregates by 42% (p = 0.002). None of the controls showed any changes in either
      sCD40L or platelet- monocyte aggregates after nCPAP therapy. CONCLUSIONS: OSA is
      associated with upregulation of circulating sCD40L levels and platelet-monocyte
      aggregation that may account for the increased incidence of cardiovascular events
      in this population. Treatment with nCPAP may alleviate this risk.

PMID- 18812692
TI  - Early detection of chronic kidney disease: results of the PolNef study.
AB  - BACKGROUND: Continuous increase in the number of patients with end-stage renal
      disease demands early detection of chronic kidney disease (CKD). The aim of the
      present study was to diagnose CKD in its earliest stages in a randomly selected
      population using a diagnostic algorithm developed by the working group. METHODS:
      An algorithm for the diagnostic procedure was created to identify patients with
      CKD requiring further nephrological care. Randomly chosen adult inhabitants of a
      city with a population of 60,000 were invited to participate in this study.
      Screening procedures included a microalbuminuria dipstick test accompanied by
      blood pressure measurement and medical questionnaire. In further diagnosis of
      CKD, estimated glomerular filtration rate (eGFR), albumin concentration in urine,
      urinalysis and ultrasound examination were used according to the algorithm.
      Multivariate logistic regression was performed to identify associations between
      participants' characteristics and albuminuria. RESULTS: Out of 9,700 invited
      subjects, 2,471 individuals participated in the PolNef study. Albuminuria was
      detected in 15.6% of the investigated population using the dipstick test and
      thereafter confirmed in 11.9% by the turbidimetric method. The modeling of
      multivariate logistic regression indicated the following independent predictors
      of albuminuria: male sex, diabetes, nocturia and hypertension. For people without
      diabetes and without hypertension, nocturia independently predicted detection of
      albuminuria. 481 people received a consultation with a nephrologist, and 96% of
      them were recognized as having CKD. At least 9% of patients with CKD had eGFR by
      MDRD <60 ml/min/1.73 m(2). Six persons were referred for further treatment
      because of newly diagnosed kidney tumor. CONCLUSIONS: CKD in early stages occurs
      frequently in the studied population. The proposed diagnostic algorithm seems to
      be a powerful tool to identify subjects at risk of CKD. The role of nocturia as
      an independent predictor of albuminuria, both in the general population and in
      people without diabetes or hypertension, should be further examined.

PMID- 18812693
TI  - Effects of sildenafil on oxidative and inflammatory injuries of the kidney in
      streptozotocin-induced diabetic rats.
AB  - BACKGROUND: Oxidative stress and inflammation are implicated in the pathogenesis
      of diabetic nephropathy. Because sildenafil citrate (Viagra) has variable
      cardiovascular benefits, including antioxidative and immunomodulating effects, we
      investigated its influence on oxidative stress and inflammation in diabetic rat
      kidney. METHODS: Streptozotocin-induced diabetic rats received sildenafil (3
      mg/kg/day in drinking water) or not (undosed water) for 8 weeks and were compared
      to age-matched nondiabetic animals. We evaluated 8-hydroxydeoxyguanosine (8-OHdG;
      for oxidative DNA damage), inducible nitric oxide synthase (iNOS) and
      nitrotyrosine (for excessive NO production and peroxynitrite formation), and
      representative chemoattractants [monocyte chemotactic protein-1, MCP-1; for
      inflammation and monocyte/macrophage infiltrations (ED-1)] in the kidney.
      RESULTS: Sildenafil-treated rats had a lower kidney-to-body weight ratio than
      untreated diabetic rats. Urinary albumin excretion in diabetic rats decreased
      significantly after sildenafil treatment without changes in systolic blood
      pressure. Sildenafil-treated rats had significantly lower urinary and renal
      cortical 8-OHdG levels than the nonsildenafil group. Sildenafil administration
      significantly attenuated the increased renal nitrotyrosine protein expression,
      positive iNOS and ED-1 staining in glomeruli and tubulointerstitium, and
      nitrotyrosine staining in tubulointerstitium. Cortical MCP-1 RNA expression in
      the sildenafil group was significantly lower than in the nonsildenafil group.
      CONCLUSIONS: Sildenafil treatment may attenuate renal damage by ameliorating
      oxidative and inflammatory injuries in diabetic rats.

PMID- 18812694
TI  - Vestibular evoked myogenic potentials are heavily dependent on type I hair cell
      activity of the saccular macula in guinea pigs.
AB  - This study applied the vestibular evoked myogenic potential (VEMP) test to guinea
      pigs coupled with electronic microscopic examination to determine whether VEMPs
      are dependent on type I or II hair cell activity of the saccular macula. An
      amount of 0.05 ml of gentamicin (40 mg/ml) was injected directly overlaying, but
      not through, the round window membrane of the left ear in guinea pigs.One week
      after surgery, auditory brainstem response test revealed normal responses in 12
      animals (80%), and elevated thresholds in 3 animals (20%). The VEMP test using
      click stimulation showed absent responses in all 15 animals (100%). Another 6
      gentamicin-treated animals underwent the VEMP test using galvanic stimulation and
      all 6 also displayed absent responses. Ultrathin sections of the saccular macula
      in the gentamicin-treated ears displayed morphologic alterations in type I or II
      hair cells, including shrinkage and/or vacuolization in the cytoplasm, increased
      electron density of the cytoplasm and nuclear chromatin, and cellular lucency.
      However, extrusion degeneration was rare and only present in type II hair cells.
      Quantitative analysis demonstrated that the histological density of intact type I
      hair cells was 1.1 +/- 1.2/4000 microm(2) in the gentamicin-treated ears, showing
      significantly less than that in control ears (4.5 +/- 1.8/4000 microm(2)).
      However, no significant difference was observed in the densities of intact type
      II hair cells and supporting cells between treated and control ears. Furthermore,
      the calyx terminals surrounding the damaged type I hair cells were swollen and
      disrupted, while the button afferents contacting the damaged type II hair cells
      were not obviously deformed. Based on the above results, we therefore conclude
      that VEMPs are heavily dependent on type I hair cell activity of the saccular
      macula in guinea pigs.

PMID- 18812695
TI  - Co-expression of HSV2 and Chlamydia trachomatis in HPV-positive cervical cancer
      and cervical intraepithelial neoplasia lesions is associated with aberrations in
      key intracellular pathways.
AB  - OBJECTIVE: Oncogenic human papillomaviruses (HPVs) are the etiological agents of
      cervical cancer. Different cofactors might be needed for malignant
      transformation, but they still remain elusive. METHODS: To delineate the role of
      Chlamydia trachomatis (CT) and herpes simplex virus type 2 (HSV2) in HPV-positive
      cervical intraepithelial neoplasia (CIN) lesions and cervical carcinoma a series
      of 149 cervical cancer and CIN biopsies were analyzed for CT and HSV2 DNA by PCR,
      and HPV genotyped by InnoLipa. Monitoring of aberrations in key intracellular
      pathways due to CT/HSV2 and HPV co-expression were analyzed with 13 biomarkers.
      RESULTS: Of the 149 samples tested, 136 were HPV DNA positive; 32/136 contained
      also CT DNA and 29 HSV2 DNA. Detection of CT was significantly (p = 0.0001)
      related to multiple-type HPV infections, while HSV2 was of borderline
      significance (p = 0.053). Of the 13 biomarkers tested, cytoplasmic and nuclear NF
      kappaB and VEGF-C were significantly increased in CT+/HPV+ lesions; p = 0.023, p
      = 0.045, and p = 0.020 as well as survivin, p = 0.026. Survivin was the only
      marker that was overexpressed also in HSV2+/HPV+ lesions, p = 0.027. CONCLUSIONS:
      CT infection favors the entry and persistence of multiple HR-HPV types, which
      leads to viral integration, inhibition of apoptosis, overexpression of E6/E7
      oncogenes and cell transformation.

PMID- 18812696
TI  - Decline of serum HBV DNA and no change apportioned by the same hepatic parenchyma
      cell volume from hepatic fibrosis stage 1 to stage 4 during the natural history
      of chronic hepatitis B.
AB  - During the initial phase of chronic hepatitis B virus (HBV) infection, serum HBV
      DNA levels are high. Contrarily, fibrosis, cirrhosis and hepatocellular carcinoma
      have been found in patients with lower serum HBV DNA levels. The aim of this
      study is to clarify HBV DNA level dynamics of serum apportioned by the same
      hepatic parenchyma cell volume (HPCV) in hepatic fibrosis stages 1-4 during the
      natural history of chronic hepatitis B. Serum HBV DNA levels were evaluated by
      real-time polymerase chain reaction. Further, serum HBV DNA levels were
      apportioned by and compared with the same HPCV in hepatic fibrosis stages 1-4,
      respectively. Serum HBV DNA levels were 8.91 x 10(6) +/- 4.37 x 10(1), 8.13 x
      10(6) +/- 7.41 x 10(1), 9.55 x 10(5) +/- 1.02 x 10(2), and 4.07 x 10(5) +/- 7.24
      x 10(1) copies/ml, respectively; there were differences among hepatic fibrosis
      stages 1-4 (p < 0.021-0.000). However, serum HBV DNA levels apportioned by the
      same volume of hepatic parenchyma cells in hepatic fibrosis stages 1-4 were 3.47
      x 10(10) +/- 8.71 x 10(2), 1.02 x 10(11) +/- 9.55 x 10(2), 1.41 x 10(10) +/- 2.57
      x 10(3), and 3.72 x 10(10) +/- 3.02 x 10(3) with HPCV proportions 65.9, 62.7,
      58.9, and 53.3%, respectively; there were no differences among hepatic fibrosis
      stages 1-4 (p > 0.203-0.967).Following the progression of hepatic fibrosis from
      stage 1 to 4, ongoing decline of HPCV is responsible for a declining trend of
      serum HBV DNA levels.

PMID- 18812697
TI  - Electroporation at low voltages enables DNA vaccine to provide protection against
      a lethal H5N1 avian influenza virus challenge in mice.
AB  - OBJECTIVE: Electroporation has been proved to enhance the efficacy of
      intramuscular delivery of DNA. However, the process of electroporation causes
      pain and discomfort to the patient receiving the treatment. Higher the
      electroporation voltages inflict greater pain, and this limits the circumstances
      in which the technique can be used clinically. The voltages generally used for
      electroporation in animals range from 100 to 1,200 V/cm. We studied the effect of
      DNA vaccination when electroporation was performed at lower voltages. METHODS:
      BALB/c mice were immunized twice by electroporation, at a 3-week interval, with
      H5N1 virus hemagglutinin (HA) DNA. One week after the booster had been given, the
      mice were challenged with a lethal dose of mouse-adapted H5N1 virus. The immune
      effects of HA DNA were evaluated by the survival rate, lung virus titer,
      bodyweight change and antibody titer of the mice. RESULTS: The higher the voltage
      used, the more able were the mice to survive the challenge. However, a
      significant degree of protection could also be achieved with a voltage as low as
      5 V. When electroporation was performed at a voltage of 10 V, an immunization
      amount of 5 microg is enough for HA DNA to provide effective protection.
      CONCLUSION: Low-voltage electroporation can induce immunity and protect mice
      effectively. There is, therefore, the potential to reduce the voltages currently
      used for DNA electroporation.

PMID- 18812698
TI  - Genotyping of hepatitis B virus--genotypes a to g by multiplex polymerase chain
      reaction.
AB  - OBJECTIVES: Eight genotypes (A-H) of hepatitis B virus (HBV) are known with
      variations in nucleotide sequences greater than 8%. Several recent publications
      found that the clinical course and outcome of antiviral therapy depended on the
      genotype of the infecting HBV strain. Large epidemiological studies will require
      the availability of a system which is rapid, reliable and can be performed on a
      large number of samples. METHODS: To establish a simple and accurate genotyping
      method, the study collected 369 HBV complete genomic sequences from the GenBank
      database. Type-specific primers were also designed that separated HBV genotypes A
      to G by multiplex polymerase chain reaction. RESULTS: By comparison with the
      traditional restriction fragment length polymorphism method, over 93% of 441
      samples were accurately genotyped by current assay, with a higher detection rate
      and sensitivity to detect mixed HBV infections. CONCLUSIONS: This methodology can
      be applied only to areas prevalent with HBV genotypes A to G. However, it
      provides an efficient alternative for clinical diagnosis and large-scale studies.

PMID- 18812699
TI  - Oligonucleotide microarrays reveal regulated genes related to inward arterial
      remodeling induced by urokinase plasminogen activator.
AB  - Accumulating evidence suggests that urokinase plasminogen activator (uPA) is
      involved in vascular remodeling and lumen stenosis after angioplasty and
      stenting. We have shown previously that increased uPA expression greatly promotes
      neointima formation and inward arterial remodeling after balloon injury. To
      evaluate the role of inflammation in early mechanisms responsible for inward
      arterial remodeling induced by uPA and elucidate the mechanisms of remodeling, we
      characterized changes in the expression profiles of 8,799 genes in injured rat
      carotid arteries 1 and 4 days after recombinant uPA treatment compared to
      vehicle. We used a standard model of the balloon catheter injury of the rat
      carotid followed by periadventitial application to the injured vessel of either
      uPA dissolved in Pluronic gel, or plain gel. Vessels were harvested and analyzed
      by immunohistochemistry, morphometry, microarray gene expression profiling and
      quantitative RT-PCR. Periadventitial application of uPA significantly reduced
      lumen size and vessel area encompassed by the external elastic lamina at both 1
      and 4 days after treatment. Inflammatory cells accumulated in the arterial
      adventitia at both 1 and 4 days after uPA treatment. On the 4th day, increases in
      the areas and arterial cell numbers of all arterial layers were found. Among 79
      differentially expressed known genes 1 day after uPA application, 12
      proinflammatory genes, including TNF-alpha and TACE, and 15 genes related to
      mitochondrial metabolism and oxidative stress regulation were identified. Four
      days after injury in uPA-treated arteries, 3 proinflammatory and 2 oxidation
      related genes were differentially expressed. We conclude that uPA likely promotes
      inward arterial remodeling by regulating oxidative stress and inflammation after
      arterial injury.

PMID- 18812702
TI  - Does abdominoplasty with liposuction of the love handles yield a shorter scar? An
      analysis with abdominal 3D laser scanning.
AB  - The aim of this study was to evaluate the combination of abdominoplasty with
      liposuction of both flanks with regards to length of scar, complications, and
      patient's satisfaction. A retrospective analysis of 35 patients who underwent
      esthetic abdominoplasty at our institution between 2002 and 2004 was performed.
      Thirteen patients underwent abdominoplasty with liposuction of both flanks, 22
      patients underwent conventional abdominoplasty. Liposuction of the flanks did not
      increase the rate of complications of the abdominoplasty procedures. We found a
      tendency toward shorter scars in patients who underwent abdominoplasty combined
      with liposuction of the flanks. Implementation of 3-dimensional laser surface
      scanning to objectify the postoperative outcomes, documented a comparable degree
      of flatness of the achieved body contouring in both procedures. 3-dimensional
      laser surface scanning can be a valuable tool to objectify assessment of
      postoperative results.

PMID- 18812700
TI  - Increased expression of renal cyclooxygenase-2 and neuronal nitric oxide synthase
      in hypertensive Cx40-deficient mice.
AB  - Cx40-deficient mice (Cx40-/-) are hypertensive due to increased renin secretion.
      We evaluated the renal expression of neuronal nitric oxide synthase (nNOS) and
      cyclooxygenases COX-1 and COX-2, three macula densa enzymes. The levels of nNOS
      were increased in kidneys of Cx40-/- mice, as well as in those of wild-type (WT)
      mice subjected to the two-kidney one-clip model of hypertension. In contrast, the
      levels of COX-2 expression were only increased in the hypoperfused kidney of Cx40
      /- mice. Treatment with indomethacin lowered blood pressure and renin mRNA in
      Cx40-/- mice without affecting renin levels, indicating that changes in COX-2 do
      not cause the altered secretion of renin. Suppression of NOS activity by N(G)
      nitro-L-arginine methyl ester (L-NAME) decreased renin levels in Cx40-/- animals,
      indicating that NO regulates renin expression in the absence of Cx40. Treatment
      with candesartan normalized blood pressure in Cx40-/- mice, and decreased the
      levels of both COX-2 and nNOS. After a treatment combining candesartan and L
      NAME, the blood pressure of Cx40-/- mice was higher than that of WT mice, showing
      that NO may counterbalance the vasoconstrictor effects of angiotensin II in Cx40
      /- mice. These data document that renal COX-2 and nNOS are differentially
      regulated due to the elevation of renin-dependent blood pressure in mice lacking
      Cx40.

PMID- 18812703
TI  - Purse-string nipple areolar reconstruction.
AB  - We present a surgical technique of nipple areolar reconstruction that uses a
      purse-string to increase areolar projection while reducing loss of nipple
      projection. A permanent purse-string is used around a modified CV flap to advance
      tissue centrally to the base of the nipple reconstruction. Two opposing
      hemiareolar island flaps are advanced toward the base of the nipple to add tissue
      volume. The resulting circumareolar full thickness skin is closed using a
      permanent purse-string suture. Synching the purse-string suture produces an
      effect similar to that of a periareolar mastopexy and enhances areolar
      projection. Eighty-two patients underwent 108 nipple areola reconstructions.
      Ninety-six percent of the patients achieved good results without any flap loss or
      suture infections. Revision surgery was necessary in 4 patients for minor
      problems including asymmetry or loss of projection. The purse-string nipple
      areolar reconstruction method described results in a high rate of maintenance of
      projection and patient satisfaction.

PMID- 18812704
TI  - Breast necrosis following left internal mammary artery harvest: a case series and
      a comprehensive review of the literature.
AB  - Breast necrosis is a rare complication following coronary artery bypass grafting,
      as the blood supply to the breast is abundant. Internal mammary artery (IMA)
      harvest has been cited as a risk factor for breast necrosis following cardiac
      procedures. We retrospectively reviewed 3 cases of breast necrosis following IMA
      harvest, performed a comprehensive literature review, and noted risk factors.
      Obesity, macromastia, diabetes, hypertension, and end-stage renal disease were
      present in all cases. Two of 3 patients had pathology suggestive of
      calciphylaxis. Despite a rich blood supply, breast necrosis following use of the
      IMA for cardiac revascularization may occur in a subset of patients. Our review
      suggests that obese patients with macromastia and end-stage renal disease may be
      at increased risk for breast necrosis following IMA harvest. As the prevalence of
      obesity increases, we may see an increase in this previously uncommon
      complication.

PMID- 18812705
TI  - Breast-feeding, self-exam, and exercise practices before and after reduction
      mammoplasty.
AB  - The current indications for reduction mammoplasty include the relief of painful
      physical symptoms of macromastia. Numerous studies have demonstrated not only
      improvement in physical symptoms following reduction mammoplasty, but
      postoperative psychological benefits as well, including increased ability to
      participate in physical activity as a result of pain relief and decreased breast
      mass. Reduction mammoplasty may have additional effects on the patient's ability
      to breast-feed and perform breast self-exam. The present study is a retrospective
      study of the effects of reduction mammoplasty on breast-feeding, breast self
      exam, physical symptoms, and physical activity. One-hundred and forty-one
      patients who underwent reduction mammoplasty at our institution between the years
      1996-2005 agreed to participate in the study. Each was asked a series of
      questions in order to assess changes in symptoms and behaviors including breast
      feeding and breast self-exam practices before and after the surgery. Patients
      were also asked questions regarding their pain symptoms and physical activity
      profiles. Ninety-seven percent of the participants claimed to have back, neck,
      and/or shoulder pain that was either significantly improved or completely
      resolved. Moreover, 100% of patients report that physical activity such as
      exercise was easier following reduction mammoplasty. Ninety-three percent of
      participants reported that performing breast self-exam following surgery was
      either the same (68%) or easier (25%) as a result of having less breast tissue.
      Eighty-nine percent of participants had no children following surgery, therefore
      effects on breast-feeding practices following reduction mammoplasty were not
      statistically significant. However, we suggest that when patients are seen in
      consultation or in the perioperative period, there is an opportunity to teach
      patients about the benefits of breast-feeding, and to assure patients that a
      pedicle flap reduction will likely allow breastfeeding. This is also a chance for
      physicians to teach patients how to perform breast self-examination and explain
      the importance of early breast mass detection.

PMID- 18812706
TI  - Types of tumors and outcome of treatment of 12 patients with nonmalignant
      fibrosing tumors in the pediatric hand.
AB  - Nonmalignant fibrosing tumors in the pediatric hand or juvenile fibromatoses are
      uncommon and so may be a challenge to the clinician. We propose a diagnostic and
      treatment approach to nonmalignant fibrosing tumors of the pediatric hand based
      on a review of 12 patients who presented with 16 distinct hand lesions. We
      performed a retrospective 7-year chart review of 12 pediatric patients all with
      nonmalignant fibrosing conditions of the hand. All patients were operated on by a
      single surgeon (D.N.) and all samples were reviewed by a single pathologist
      (E.P.). Twenty-eight surgical procedures were performed on 12 patients. Lesions
      were classified by location (7 palmar, 9 dorsal) as well as clinicopathologic
      characteristics. It is imperative to have a broad differential when entertaining
      the diagnosis of juvenile fibromatosis. Most important, a diagnosis of true
      cancer must be ruled out. Other mimickers of this process (eg, juvenile
      rheumatoid arthritis) must also be considered. Most evaluations begin with
      magnetic resonance imaging and biopsy but a careful history is, as always, a key
      part of the evaluation. Some lesions may be observed once a diagnosis has been
      made. When surgical excision is indicated, wide resection is necessary. This may
      then require flap reconstruction with tendon and joint repair.

PMID- 18812707
TI  - Resurfacing hemipulp losses of the thumb: the cross finger flap revisited:
      indications, technical refinements, outcomes, and long-term neurosensory
      recovery.
AB  - Volar-oblique injuries of the thumb pulp are particularly disabling. Many methods
      have been described to treat these injuries and provide return of sensibility.
      The conventional cross finger flap is an established technique and is well suited
      for intermediate-sized partial pulp losses. We review our experience with this
      flap and describe technical refinements that have contributed to improved early
      outcome and long-term neurosensory recovery. Thirty patients underwent 31 cross
      finger flaps to the thumb for volar-oblique pulp defects. Defect sizes ranged
      from 1.5 to 5 cm in length and 1.5 to 3 cm in width. Dorsal skin of the index
      finger proximal phalanx was used in 26 patients, index finger middle phalanx in 2
      patients, and long finger middle phalanx in 3 patients. Nine patients were
      available for long-term follow-up and were subjected to functional assessment
      (DASH questionnaire), sensitivity testing (2-point discrimination, Semmes
      Weinstein monofilament testing), and range of motion evaluation. Thirty of 31
      flaps survived. In 1 patient, trauma to the attached flap from the long finger
      middle phalanx resulted in flap ischemia. This was revised with a fresh cross
      finger flap from the index finger proximal phalanx. Employed patients were able
      to return to their original jobs. Recalled patients (n = 9) were assessed at a
      mean of 29 months after surgery (range, 12-70 months). All recalled patients
      regained normal sensibility on 2-point discrimination testing. Functional outcome
      was satisfactory in 8 patients (DASH score, 0-20). The last patient (DASH score,
      61.67) complained of hypersensitivity and cold intolerance that affected his
      work. The conventional cross finger flap provides reliable coverage for volar
      oblique hemipulp losses of the thumb, with patients regaining at least protective
      sensibility in the long term. The proximal and middle phalanges of both the index
      and long fingers may serve as donor sites, allowing the surgeon to best select
      skin cover based on defect size and options in finger positioning.

PMID- 18812708
TI  - A modified approach of the reverse dorsal metacarpal island flap: anatomical
      basis and application in 24 cases.

PMID- 18812709
TI  - Which venous system to choose for anastomosis in head and neck reconstructions?
AB  - It has been postulated that venous thrombosis in free flap surgery necessitates
      the use of 2 venous anastomoses into different venous systems. We retrospectively
      analyzed a single surgeon's 10-year experience (August 1993 to August 2003) in
      primary free flap reconstruction for malignant tumors of the head and neck. Of
      492 primary reconstructions that did not need a vein graft, vein loop, or
      cephalic turnover procedure, 251 used the internal jugular venous system as
      venous outflow, 140 used the subclavian system as outflow, and 101 used both. Two
      hundred thirty-eight of 251 (95%) of flaps utilizing the internal jugular venous
      system for outflow were successful compared with 129 of 140 (92%) of flaps
      utilizing the subclavian system. Where both venous systems were used the success
      rate was 101 of 101 (100%) (P < 0.05). Where possible, a second venous
      anastomosis should be performed utilizing both venous drainage systems.

PMID- 18812710
TI  - Surgical treatment of angiosarcoma of the scalp: less is more.
AB  - Angiosarcomas (AS) of the scalp are rare tumors with an extremely poor prognosis
      mostly affecting elderly patients. Given the special anatomic nature of the blood
      supply to the scalp, it must be presumed that the tumor has already spread at the
      time of the initial presentation. We report a simple and fast surgical procedure,
      which places only a minimum burden on the patient. In 19 patients, we performed a
      resection of the external table with the defect being covered immediately by a
      split skin graft. The average stay in hospital amounted to 12.2 days. The
      postoperative period free of recurrences was 2.7 months on average. The average
      survival period after resection was 17.5 months. In view of the difficult
      diagnosis, an often delayed therapy and the rapid formation of metastases, a time
      saving procedure with a low rate of complications should be given preference over
      other reconstructive methods.

PMID- 18812711
TI  - A comparative study of the medial crura of alar cartilages in unilateral
      secondary cleft nasal deformity: the validity of medial crus elevation.
AB  - The purpose of this study was to confirm whether the medial crus on the cleft
      side is primarily hypoplastic compared with the noncleft side and to evaluate the
      displacement of the medial crus on the cleft side presenting the validity of the
      "medial crus elevation" method. Thirty unilateral cleft lip nasal deformity
      patients underwent medial crus elevation. The thickness, width, and length of the
      medial crus on both sides were measured. The difference in the height of both
      foot plates was also measured. There were no significant differences between the
      cleft and noncleft sides in width, thickness, or length except proximal
      thickness. The foot plate on the cleft side was displaced downward. The medial
      crus on the cleft side is not hypoplastic, and it is merely displaced downward.
      These results show the validity of the medial crus elevation method for the
      correction of secondary nasal deformities in cleft patients.

PMID- 18812712
TI  - Basal cell carcinoma and rhinophyma.
AB  - Rhinophyma, the end stage in the development of acne rosacea, is characterized by
      sebaceous hyperplasia, fibrosis, follicular plugging, and telangiectasia.
      Although it is commonly considered a cosmetic problem, it can result in gross
      distortion of soft tissue and airway obstruction. Basal cell carcinoma (BCC) is a
      rare finding in patients with rhinophyma. The objective of this study is to
      review the literature of BCC in rhinophyma and report on a case. A 70-year-old
      male presented with long-standing rosacea that resulted in a gross nasal
      deformity. The patient suffered from chronic drainage and recurrent infections
      that failed conservative treatment with oral and topical antibiotics. The patient
      decided to proceed with surgical intervention and underwent tangential excision
      and dermabrasion in the operating room. Since 1955 there have been 11 cases
      reported in the literature. In our case, the pathology report noted that the
      specimen had an incidental finding of a completely resected BCC. The patient did
      well postoperatively and at follow-up remains tumor-free. Despite the uncommon
      occurrence of BCC in resection specimens for rhinophyma, we recommend that all
      specimens be reviewed by a pathologist. If BCC is detected, re-excision may be
      necessary and careful follow-up is mandatory. Larger studies would be needed to
      determine the correlation between the 2 conditions.

PMID- 18812713
TI  - Endoscopic excision of cheek lipomas.
AB  - Although the removal of forehead and brow benign tumors using an endoscopic
      technique has proven to be valuable, the efficacy of an endoscopic excision for
      cheek masses is unclear. A retrospective review was performed on 8 patients with
      a lipoma (7) and a foreign body granuloma (1) located at the cheek region. There
      were 7 men and 1 woman with a mean age of 34.8 years (range, 22-54 years). All
      the excisional procedures were performed with an endoscope through 2 small
      incisions, one on the hair-bearing sideburns and the other behind the earlobe.
      The masses varied from 0.7 x 0.7 cm to 4.0 x 3.0 cm in size. There were no
      intraoperative or postoperative complications, and no recurrence was detected
      after a 5- to 61-month follow-up. An endoscopically assisted excision of cheek
      lipomas is an effective procedure and might be a good alternative to the more
      conventional procedures.

PMID- 18812714
TI  - Topical imiquimod therapy for lentigo maligna.
AB  - Lentigo maligna (LM) presents a challenge for complete surgical excision.
      Imiquimod is a topical immune-response modifier that acts on the immune system.
      We report our experience using imiquimod 5% cream as a surgical alternative for
      treatment of LM. Consecutive patients between December 2004 and February 2006
      with LM were treated with topical imiquimod. Data on patient and lesion
      characteristics, side effects of therapy, posttreatment biopsy results, and
      follow-up was collected. Seven patients were treated with imiquimod 5 nights/wk
      for 12.4 weeks. Complete histologic and clinical resolution was seen in 86% (6 of
      7 patients), at 19.1 months follow-up. Side effects included erythema (86%) and
      crusting (71%), resulting in dose alteration in 71% of patients. Topical
      imiquimod therapy demonstrates a high response rate for treatment of LM, with
      tolerable side effects. Further investigation into its efficacy in the treatment
      of LM in controlled clinical trials is warranted.

PMID- 18812715
TI  - Successful truncated osteomyelitis treatment for chronic osteomyelitis secondary
      to pressure ulcers in spinal cord injury patients.
AB  - Time-tested treatments for chronic osteomyelitis involve prolonged courses of
      costly antibiotic treatment. Although such treatment remains unquestioned in
      acute osteomyelitis, it is an excessive regiment for chronic osteomyelitis. With
      appropriate surgical debridement and careful operative care, antibiotic treatment
      can be truncated in diagnoses of chronic osteomyelitis. This study represents the
      clinical practice of the pressure ulcer management program at Rancho Los Amigos
      National Rehabilitation Center in dealing with this difficult problem. One
      hundred fifty-seven patients with similar pressure ulcer wounds were studied
      retrospectively. Three groups of patients with pathologic diagnoses of acute
      osteomyelitis, chronic osteomyelitis, and negative osteomyelitis were compared
      for (1) postoperative stay, (2) wound infection, (3) wound breakdown requiring
      reoperation, and (4) same-site ulcer recurrence. In all cases, shallow bone
      shavings were sent for diagnosis via histologic study, and deep shavings were
      also sent to ensure adequate bone debridement and microbiologic study. All ulcers
      were subsequently closed with muscle and/or myocutaneous flaps. The negative and
      chronic osteomyelitis groups were treated with 5 to 7 days of IV antibiotics,
      whereas the acute group underwent a full 6-week course according to bone
      bacteriological culture and sensitivity. There was no statistical difference
      between the chronic osteomyelitis group and the control (negative) osteomyelitis
      group with respect to postoperative stay (70 days for chronic group, 72.4 for
      control), wound breakdown rate (10.7% for chronic, 10.2% for control), or ulcer
      recurrence (1.8% for chronic, 4.1 for control). The acute osteomyelitis group
      incurred longer hospital stays, greater incidence of wound breakdown, and
      statistically significantly greater ulcer recurrence (78.6 days, 13.2% and 17.0%,
      respectively). In cases of pressure ulcer management with bony involvement, bone
      pathologic diagnosis of chronic osteomyelitis allows for a shorter antibiotic
      course with better results when the offending tissue has been adequately debrided
      and closed with viable tissue flap coverage, than simple long-term (4-6 weeks)
      antibiotic treatment. Because of the extreme contaminated nature of these wounds,
      if such therapy works in these patients, it may be applicable to chronic
      osteomyelitis in more varied contaminated surgical cases involving bone.

PMID- 18812716
TI  - The reverse sural flap: modifications to improve efficacy in foot and ankle
      reconstruction.
AB  - The aim of this work is to evaluate the efficacy of the reverse sural flap in
      covering defects in the foot and ankle region when certain technical
      modifications are employed. We provide a retrospective review of 32 consecutive
      reverse sural flaps for foot and ankle defects, and compare the technique and
      results with other reports. There were 23 fasciocutaneous flaps, 7 fascial flaps,
      and 2 tissue-expanded flaps. Four flaps (12.5%) suffered significant flap loss,
      and 4 patients had delayed healing.Several modifications are suggested to
      increase the versatility of the sural flap in covering foot and ankle defects,
      including preserving the mesentery connecting the sural nerve to the deep fascia,
      inclusion of skin of the upper third of the leg, limiting pedicle width to 2 cm
      with preservation of a tongue-like skin process all along its length, and
      generous release of the fascia over the peroneal compartment. In addition, we
      describe the use of tissue expanded sural flaps.

PMID- 18812717
TI  - Spectrophotometric intracutaneous analysis: a novel imaging technique in the
      assessment of acute burn depth.
AB  - The noncontact spectrophotometric intracutaneous analysis scope (SIAscope) is a
      novel portable imaging device that rapidly produces images of the blood and
      melanin content of large areas of skin. The estimation of burn depth is often
      difficult in the clinical setting, and this pilot study was conducted to assess
      the potential for the SIAscope in aiding burn assessment. Nine patients with a
      variety of burn injuries had images taken of their acute burns within 48 hours of
      injury, both with a noncontact SIAscope and a laser Doppler perfusion imaging
      system (LDPI). Results showed that superficial partial thickness burns had
      increased hemoglobin and loss of melanin on SIAgraphs, whereas deep partial
      thickness burns had more pronounced hemoglobin concentrations and apparent
      melanin increases, helping to differentiate these 2 burn types. The SIAscope, a
      relatively inexpensive, portable device, has the potential to be a highly useful
      clinical adjunct in the bedside estimation of acute burn depth.

PMID- 18812718
TI  - Extended vertical trapezius fasciocutaneous flap (back flap) in face and neck
      burn scar reconstruction.
AB  - Elevation of the skin along with its deep fascia vascular network is a recent
      facility for flap design. The longitudinal trapezius fasciocutaneous flap was
      first introduced in 1996; at that time it did not receive much attention,
      although it has many significant benefits compared with other available
      procedures. Sixteen trapezius fasciocutaneous flaps were elevated in 15 patients
      for reconstruction of severe scarring of the neck and midface. All flaps were
      based on the deep branch of the transverse cervical artery and included the
      overlying fascia of the trapezius muscle. Delaying was applied for very long
      flaps. Two flaps developed minimal distal necrosis (<5 cm) due to longer pedicles
      (>10 cm below the muscle border). The results indicate that an extra-long back
      fascia flap based on the descending branch of the transverse cervical artery
      could be formed, which would be long enough to reconstruct the entire neck and
      safely transfer it to the midface. The vertical trapezius fasciocutaneous flap,
      with its abundant tissue, excellent blood supply, anatomic proximity, wide arc of
      rotation, and hidden donor site scar, provides a simple and reliable method for
      primary reconstruction of various midface and neck defects.

PMID- 18812719
TI  - Expanded scarred or skin-grafted forehead flap for nasal reconstruction in severe
      postburn facial deformity.
AB  - Loss of the nose is one of the sequelae of the severe facial burn and requires
      total nasal reconstruction. Many traditional techniques were used but the result
      was not good in terms of skin color and texture match. For those patients who
      suffered from full face burn associated with nasal defect but retained smooth
      atrophic scars or grafted skin on the integrate frontalis, the expansion of the
      scarred forehead was chosen to reconstruct a new nose. Generally, the patients
      underwent 3 stages of operation. Fifty-two cases of nasal defects were
      reconstructed successfully with satisfactory results. The reconstructed nose
      manifested similar color and texture to the postburn face, and the new noses had
      no sign of shrinkage, flattening, or collapse. Expanded scarred forehead flap for
      nasal reconstruction could obtain a new nose with similar skin color and texture
      to its adjacent postburn face.

PMID- 18812720
TI  - Hypoglossal-facial nerve anastomosis in the rabbits using laser welding.
AB  - The aim of this study is to compare laser nerve welding of hypoglossal-facial
      nerve to microsurgical suturing and a result of immediate and delayed repair, and
      to evaluate the effectiveness of laser nerve welding in reanimation of facial
      paralysis of the rabbit models. The first group of 5 rabbits underwent immediate
      hypoglossal-facial anastomosis (HFA) by microsurgical suturing and the second
      group of 5 rabbits by CO2 laser welding. The third group of 5 rabbits underwent
      delayed HFA by microsurgical suturing and the fourth group of 5 rabbits by laser
      nerve welding. The fifth group of 5 rabbits sustained intact hypoglossal and
      facial nerve as control. In all rabbits of the 4 different groups, cholera toxin
      subunit B (CTb) was injected in the epineurium distal to the anastomosis site on
      the postoperative sixth week and in normal hypoglossal nerve in the 5 rabbits of
      control group. Neurons labeled CTb of hypoglossal nuclei were positive
      immunohistochemically and the numbers were counted. In the immediate HFA groups,
      CTb positive neurons were 1416 +/- 118 in the laser welding group (n = 5) and
      1429 +/- 90 in the microsurgical suturing group (n = 5). There was no significant
      difference (P = 0.75). In the delayed HFA groups, CTb positive neurons were 1503
      +/- 66 in the laser welding group (n = 5) and 1207 +/- 68 in the microsurgical
      suturing group (n = 5). Difference was significant (P = 0.009). There was no
      significant difference between immediate and delayed anastomosis in the laser
      welding group (P = 0.208), but some significant difference was observed between
      immediate and delayed anastomosis in the microsurgical suturing group (P =
      0.016). Injected CTb in intact hypoglossal neurons (n = 5) were labeled 1970 +/-
      165. No dehiscence was seen on the laser welding site of nerve anastomosis in all
      the rabbits as re-exploration was done for injection of CTb. This study shows
      that regeneration of the anastomosed hypoglossal-facial nerve was affected
      similarly by either laser welding or microsurgical suturing in immediate repair;
      however, the welding was more effective especially in delayed repair.

PMID- 18812721
TI  - The effect of continuous release of recombinant human epidermal growth factor (rh
      EGF) in chitosan film on full thickness excisional porcine wounds.
AB  - The purpose of this article is to evaluate the effect of continuously released
      recombinant human epidermal growth factor (rh-EGF) in chitosan film in full
      thickness porcine wounds. A total of 10 domestic pigs (Yorkshire species)
      weighing 18 to 22 kg between the ages of 50 to 60 days were used. The wounds were
      divided into 3 groups and treated selectively with rh-EGF in chitosan film (EGF
      20 ug/wound/d), chitosan film without rh-EGF, or remained as the control group.
      One hundred percent healing time was observed, and hematoxylin and eosin and Anti
      Ki-67 antibody immunohistochemical staining were performed. The 100% healing time
      and Anti Ki-67 antibody immunohistochemical staining showed statistical
      significance of the rh-EGF chitosan film-treated group against the control group
      (P < 0.05). But it did not reveal any statistical significance over the chitosan
      film-treated group. In this preliminary study, although continuous release of rh
      EGF in chitosan film accelerates epithelialization, the benefit of the
      combination of rh-EGF in chitosan cannot be determined over the use of chitosan
      alone. Further analysis using complex wound models such as diabetes or infection,
      which may have different pathology in healing, will be needed to evaluate the
      potential benefit/synergistic effectiveness.

PMID- 18812723
TI  - Quantification of the osmotic expansion in implants filled with polyethylene
      glycol.
AB  - High reoperation rates continue to agonize the field of breast augmentation
      surgery. Patient dissatisfaction is a contributing factor for reoperations. This
      is often attributable to patients' desire to be larger after the augmentation.
      Polyethylene glycol (PEG) is a potential alternative breast implant filler under
      investigation. It has been shown to swell secondary to osmotic expansion when it
      is placed in vivo. We hypothesize that there is a finite expansion in this
      process. An experimental study was designed utilizing an in vitro model to
      quantify the rate and volume of the osmotic expansion of PEG-filled implants.
      Seventeen silicone elastomer shells were filled with various percent
      concentration and molecular weight PEG/saline solutions. These implants were kept
      in saline baths at varying temperatures to assess the effect of temperature on
      osmotic expansion. Daily weights were recorded to quantify the expansion and
      determine if a plateau was reached. Implant expansion was observed to plateau in
      all groups tested. Implants filled with 85% concentration PEG solutions
      demonstrated a uniform expansion at a rate of 0.032 to 0.037 g/d. Implants filled
      with 85% concentration PEG stored at human core temperature (37 degrees C) gained
      on average 6.2% to 7.6% of their original weight. Implants stored at 4 degrees C
      expanded to a higher volume than implants stored at 37 degrees C (P < 0.01).
      Implants filled with 50% concentration PEG solution gained only 2.7% of their
      original weight (P < 0.01). PEG-filled implants undergo controlled osmotic
      expansion to a final predictable weight in vitro. Higher concentration PEG
      induces greater volume expansion. A colder environment also induces greater
      volume expansion. PEG is biologically inert and may be an alternative filler for
      breast implants. The predictable expansion process may be beneficial in breast
      augmentation that may alleviate patient dissatisfaction about breast size once
      postoperative edema resolves.

PMID- 18812722
TI  - A new bone-ligament-bone autograft from the plantar plates of the toes and its
      potential use in scapholunate reconstruction: an anatomical study.
AB  - The study was performed to investigate a new bone-ligament-bone autograft from
      the plantar plate of the toes. The anatomic properties of the plantar ligaments
      and the technical feasibility to harvest a bone-ligament-bone graft were examined
      to evaluate the potential use of this graft for a suitable reconstruction of the
      scapholunate (SL) interosseous ligament. The plantar plate of the
      metatarsophalangeal joints of the second to fifth toe and the proximal
      interphalangeal joints of the second to fourth toe were examined in 20 cadaver
      feet (15 fresh and 5 embalmed cadavers) and measurements such as length,
      thickness, and width were taken. The average length of the plantar ligaments of
      the proximal interphalangeal joint was 0.63 cm (D3) and 0.62 cm (D4). The length
      of the plantar plates of the proximal interphalangeal joint of the third and
      fourth toe was found to be similar to that of the SL ligament. In addition to the
      measurements, a bone-ligament-bone autograft of the plantar plates of the
      metatarsophalangeal joint was designed as an SL-ligament substitute and
      successfully transplanted into cadaveric wrists. This new autograft is
      intercalated between the scaphoid and lunate and, contrary to all previous
      methods, not simply superimposed upon them. Length of the plantar plates was
      considered by the authors as the main criteria for selection of the new bone
      ligament-bone graft. The plantar plate of the proximal interphalangeal joint of
      the third and fourth toe showed a similar length compared with the SL ligament.
      Therefore, it can be concluded from the data that this bone-ligament-bone graft
      can be a suitable replacement for the SL ligament.

PMID- 18812724
TI  - Infantile digital fibromatosis.
AB  - Infantile digital fibromas are rare benign neoplasms that occur principally in
      children and are usually confined to the digits. These lesions are similar in
      appearance to several benign and malignant lesions, and biopsy is often required
      to confirm the diagnosis. The tumor is composed of myofibroblasts, which contain
      pathognomonic intracellular inclusion bodies. There is a strong tendency for
      recurrence after excision. We present a 2-year-old who developed extensive
      involvement of all 4 extremities after syndactyly release. This case is unusual
      in that the lesions occurred postsurgically and were substantially more extensive
      than those previously described.

PMID- 18812725
TI  - Free pectoral skin flap in the rat based on the long thoracic vessels: a new flap
      model for experimental study and microsurgical training.

PMID- 18812729
TI  - Measurement of quality in pediatric cardiac surgery: understanding the threats to
      validity.
AB  - The initiation of pay for participation and the expected move to pay for
      performance have increased the stakes for and amplified the importance of valid
      quality measures. Assessing the outcomes of clinical care is difficult and relies
      on the methods of observational epidemiology. Because pediatric cardiac surgery
      operations are performed relatively infrequently at individual hospitals and
      mortality rates are generally low, understanding the limitations inherent in the
      design of observational studies is imperative. Detailed study of the processes of
      care by multicenter, multidisciplinary quality improvement initiatives may
      augment national databases in improving outcomes.

PMID- 18812728
TI  - Fourth International Conference on Pediatric Mechanical Circulatory Support
      Systems and Pediatric Cardiopulmonary Perfusion.

PMID- 18812730
TI  - Results with all blood retrograde microplegia as a myocardial protection strategy
      for complex neonatal arch reconstruction.
AB  - Neonatal arch reconstructions present a challenge for myocardial protection. We
      report our results for eight patients treated with intermittent cold all blood
      retrograde cardioplegia during arch reconstruction using continuous selective
      normothermic cerebral perfusion. Over a 10-month period eight consecutive
      neonates underwent complex arch reconstruction. Mean age was 8.4 days (range 2
      23); weight 3.1 kg (range 2.7-3.8). Diagnosis was hypoplastic left heart syndrome
      (5), interrupted aortic arch/ventriculoseptal defect (2), and complex AP window
      (1). Mean cardiopulmonary bypass time was 149 minutes (range 80-201), mean cross
      clamp time was 74 (range 51-101). All patients had primary chest closure and none
      required extra-corporeal membrane oxigenation. One patient (12%) had a period of
      low cardiac output syndrome, which resolved with high dose inotropes. All
      patients were discharged alive and well. Intermittent all blood retrograde
      microplegia is an effective myocardial protection strategy for complex neonatal
      arch reconstruction. Postoperative myocardial function is very good. This
      protection approach facilitates continuous selective normothermic cerebral
      perfusion.

PMID- 18812731
TI  - Intraoperative techniques to assess cardiac function-feasiblity of strain rate
      imaging in the perioperative period in children.
AB  - The noninvasive assessment of cardiac function during mechanical circulatory
      support is challenging because conventional markers (like ejection fraction) are
      significantly load-dependent. Yet loading conditions are abnormal and change
      during support and weaning process. Tissue Doppler and strain rate imaging are
      echocardiographic techniques that permit quantitation of regional wall motion.
      Peak systolic strain rate (SR) is a fairly load-independent marker of ventricular
      systolic function in experimental validation studies. We hypothesized that SR
      changes would improve assessment of right and left ventricular function during
      mechanical circulatory support. Color tissue Doppler images were acquired before
      surgery, 8 and 24 hours postoperatively in 18 children undergoing open heart
      surgery. Clinically, all patients were hemodynamically stable and on low doses of
      inotropics without death or resuscitation events. Wall motion analysis revealed a
      significant drop of peak systolic velocities and SR postoperatively in both
      ventricles. On the next day, all parameters improved with regional differences.
      SR appeared to be more sensitive to changes than velocities. In conclusion,
      tissue Doppler imaging appears to be a sensitive marker of ventricular mechanics
      in children and may improve perioperative monitoring. It offers a method to
      quantitatively assess left and right ventricular performance and may help to
      compare different cardio-protective strategies.

PMID- 18812732
TI  - Operative risk and outcome of surgery in adults with congenital valve disease.
AB  - To define risk and outcome of surgery in adults with congenital valve disease
      (CVD), experience between 2002 and 2005 with 371 CVD operations (288 males, aged
      56 +/- 9 years) was compared with 2102 for acquired valve disease (AVD) (69 +/-
      22 years, p = 0.02). Diagnosis included: bicuspid aortic valve (BAV), 337, s/p
      ToF repair, 11; atrio-ventricular valve dysfunction, 10; other, 13. Associated
      lesions were present in 259 patients (70% vs. 17%, p = 0.001): ascending aorta,
      205; right ventricular outflow tract obstruction, 40; coronary artery, 34;
      mitral/tricuspid valve, 27; septal defect, 17; subaortic stenosis, 4; aortic
      arch, 4; other, 3. Fifty-two patients (14% vs. 2.5% AVD, p = 0.001) had undergone
      75 prior operations (1.4/patient) and 14 (3.8% vs. 1.9% AVD, p = 0.04) required
      urgent/emergent surgery (endocarditis, dissection). Valve repair was done in 36
      (10% vs. 3% AVD, p = 0.02) and replacement in 335: stentless solution (native,
      autograft, xenograft) was offered to 101 (29%) patients. In BAV, partial root
      replacement was associated in 63, complete in 77 and ascending aorta in 92. Three
      (0.8%) hospital deaths occurred (vs. 1.9% AVD, p = 0.2) due to endocarditis.
      Twenty-six patients (7.0% vs. 10.8% AVD, p = 0.003) experienced complications
      (cardiac, 7; neurologic, 6; respiratory, 5; renal, 3; sepsis/multiple organ
      failure (MOF), 2; hemorrhage, 8). Urgent/emergent surgery predicted hospital
      mortality (p = 0.001). During 5-year follow-up (average 2.6 +/- 1.8 years), there
      was one late cardiac death and three reoperations (98% free). Despite higher
      prevalence of associated procedures, reoperation and emergent indication,
      operative risk in CVD is lower than in AVD, possibly because of younger age.
      Stentless valve surgery, allowing normal life-style (e.g., exercise, pregnancy),
      is increasingly preferred.

PMID- 18812733
TI  - Effect of different albumin concentrations in extracorporeal circuit prime on
      perioperative fluid status in young children.
AB  - This study examined the effects of different dosages of albumin priming for
      extracorporeal circuit (ECC) on perioperative fluid status and fluid management
      in young children. A total of 151 consecutive pediatric patients (2-36 months
      old) scheduled for open heart surgery, were divided into two groups randomly, to
      receive either a 3% albumin solution (L group, n = 68) or a 5% albumin (H group,
      n = 83). Perioperative fluid intake, urine output, blood loss, diuretic dosage,
      the use of allogeneic blood products, ultrafiltration, and daily balance were
      recorded for 24 hrs in intensive care unit (ICU). Serial hematocrits, colloid
      osmotic pressure (COP) were measured. Outcomes and complications were documented.
      There were no significant differences in demographics, types of surgical
      procedures, baseline data such as hemoglobin, COP, and serum albumin. Patients in
      H group had significantly higher COPs, less urine output and more diuretic usage
      during operation and postoperatively (p < 0.05); at 6 hrs postoperatively, there
      were no differences between two groups. No statistically significant differences
      were found between the two groups in blood loss and the amount of allogenic blood
      products infused, length of mechanical ventilation, ICU or hospital stay,
      complications, or mortality. Higher concentration of albumin prime in ECC showed
      decreased positive fluid balances, but produced less urine output and required
      more diuretic usage postoperatively. Thus, no significant clinical benefit
      resulted from the increased dosage.

PMID- 18812734
TI  - The influence of neurophysiologic monitoring on the management of pediatric
      cardiopulmonary bypass.
AB  - We describe a process by which we sought to determine how the addition of
      intraoperative neurophysiologic monitoring (IONM) impacted the management of
      cardiopulmonary bypass (CPB) during pediatric cardiac surgery. While maintaining
      a consistent team of surgeons, anesthesiologists, nurses, and perfusionists, a
      multi-modal, IONM program was established consisting of Near Infrared
      Spectroscopy, Transcranial Doppler, and eight channel electroencephalography. A
      retrospective review of cases from 1 year before the institution of the IONM
      program was compared with data obtained from cases performed after
      neurophysiologic monitoring was established as a standard of care for pediatric
      patients on CPB. This comparative analysis of CPB management revealed a
      significant increase in the use of donor blood added to the CPB circuit prime as
      well as in the maintenance of a higher hematocrit during the bypass period after
      the implementation of IONM. These changes in the management of pediatric CPB
      correlated with recommendations of previous studies that examined postoperative
      neurophysiologic outcomes, suggesting that these changes were not only consistent
      with best practices, but that the presence of IONM data facilitated a transition
      to evidence-based practice.

PMID- 18812735
TI  - The myocardial protection of HTK cardioplegic solution on the long-term ischemic
      period in pediatric heart surgery.
AB  - Cardioplegic reperfusion during a long term ischemic period interrupts cardiac
      surgery and also increase cellular edema due to repeated administration. We
      reviewed the clinical experiences on myocardial protection of one single
      perfusion with histidine-ketoglutarate-tryptophan (HTK) for infants. This
      retrospective study included 118 infants who underwent open-heart surgery between
      January 2004 and December 2007. We divided the entire cohort into two groups: In
      group H (n = 63), myocardial protection was carried out with one single perfusion
      with HTK solution, and in group S (n = 55) with conventional St. Thomas
      crystalloid cardioplegia. The duration of cardiopulmonary bypass (CPB) did not
      differ between these two groups, but the duration of aortic cross-clamping time
      in group H was significantly shorter than that in group S (p < 0.05). During
      reperfusion, the spontaneous re-beating rate was higher in group H (p < 0.05).
      There were no differences in doses of inotropic agent and creatinekinase (CK)
      values on postoperative day 1 between these two groups, but the level of CK in
      group H was significantly less than that in group S on postoperative day 2 (p <
      0.01). The mortality in group H was lower than in group S (p < 0.05). The HTK
      group had shorter cross-clamping time and more frequent spontaneous
      defibrillation than St. Thomas group. We propose that HTK is valid for some
      complicated cardiac surgeries with long term cross-clamping time.

PMID- 18812736
TI  - Ventricular assist device implantation in the pediatric population: does pump
      size selection and associated hemodynamics impact outcomes?
AB  - The use of pediatric ventricular assist devices (VADs) continues to evolve with
      the availability of smaller blood pumps. We examine the correlation of implanting
      appropriate sized blood pumps with a lower incidence of VAD related complications
      (VADRC). A 7-year retrospective review was undertaken for all pediatric VAD
      patients. Optimal VAD hemodynamics were defined as cardiac index of 2.7 L/m2 and
      rate of 80 beats per minute (bpm) with complete fill/empty of the blood pump.
      Patient/blood pump size match, VAD rate and fill/empty ratios were calculated
      (optimum = 1.0) and then correlated with incidence of VADRC. The study included
      22 patients, mean age 9.77 years (6 mo-18 yrs) and mean body surface area (BSA)
      of 1.14 m2 (0.14 m2-2.32 m2), who underwent VAD implantation. VADRC included
      death while on support (n = 5), bleeding requiring reoperation (n = 8), hemolysis
      (n = 2), neurologic events (n = 2), thrombus formation (n = 3), and infection (n
      = 3). Six patients were bridged to transplant without any VADRC. This subset of
      patients had a mean blood pump size match ratio of 0.98, VAD rate ratio of 0.92
      and fill/empty ratio of 1.00. Patients with VADRC (n = 16) were found to have a
      mean blood pump size match ratio of 0.72, VAD rate ratio of 0.72 and fill/empty
      ratio of 0.78. We report a series of pediatric patients with wide ranging BSA
      receiving VAD implantation. Selection of appropriate sized blood pumps can be
      correlated with decreased VADRC.

PMID- 18812737
TI  - Preliminary single center North American experience with the Berlin Heart
      pediatric EXCOR device.
AB  - For children requiring mechanical circulatory support as a bridge to cardiac
      transplantation in North America, options previously were limited to
      extracorporeal membrane oxygenation (ECMO) or centrifugal pump ventricular
      assist, both of which were suitable for only very short term application and were
      associated with significant complications and limitations. The Berlin Heart EXCOR
      ventricular assist device (VAD) was recently introduced into practice in North
      America to address this deficiency. We report a preliminary single center
      experience with the EXCOR in 17 children, 13 who received only a left-sided pump
      and four who required biventricular support. Before EXCOR placement, six patients
      were on ECMO, and one was on a centrifugal VAD. Eleven children were bridged to
      transplantation, one was bridged to recovery, and one remains on support. Three
      children died during support and one died after explantation. There was one late
      death nearly 2 years after transplant. Complications included stroke in seven
      patients, two of which were ultimately fatal. Five patients required re
      operations for bleeding or evacuation of hematoma. Despite a disappointing rate
      of neurologic morbidity, our preliminary experience with the EXCOR has been very
      encouraging.

PMID- 18812738
TI  - Development of an interprofessional pediatric ventricular assist device support
      team.
AB  - Caring for pediatric patients with a ventricular assist device (VAD) requires a
      collaborative approach from an interprofessional team to ensure maximum patient
      safety and optimal outcomes. Initiating a VAD program is challenging, due to the
      complex medical and technical nature of this device and associated learning
      needs. At our institution, the development of the interprofessional VAD support
      team was established in four phases. Initial Education, Core Team Formation,
      Expansion, and Evaluation. A "core VAD team" was created after the initial
      education at an established VAD center. In a third step, all efforts were
      directed toward increasing the number of health care professionals caring for the
      VAD patients in the Cardiac Critical Care setting and on the Cardiac ward. The
      last phase consists of ongoing evaluation. Several key areas imperative to the
      care of a patient on a VAD were identified and further elaborated. The complex
      care of a patient on a VAD needs a specialized team approach to cover all patient
      care needs. Ongoing interprofessional education continues to improve competency
      of care. Continuity of care was assured on all levels of service to ensure the
      best possible outcomes.

PMID- 18812739
TI  - Microemboli generation, detection and characterization during CPB procedures in
      neonates, infants, and small children.
AB  - In our laboratory, we study different factors that influence the microemboli
      counts in the extracorporeal circuit using a simulated pediatric cardiopulmonary
      bypass (CPB) model identical to the one used in our operating rooms. For
      monitoring and classification of microemboli, we use the novel Emboli Detection
      and Classification (EDAC) Quantifier system which allows for real-time
      monitoring, localization, and size characterization of microemboli as small as 10
      microm. Our results show that high flow rates, low perfusate temperature, use of
      vacuum assisted venous drainage (VAVD), use of roller pump, and pulsatile flow
      results in higher microemboli counts at postpump site. Microemboli counts at
      postoxygenator, and postfilter sites are significantly less. This indicates that
      hollow fiber membrane oxygenator was able to remove most of the microemboli, and
      an opened arterial filter purge line augments the removal of microemboli that
      were not captured by the oxygenator. Majority of the microemboli detected at all
      sites were <40 microm in size. Based on the results of our studies, we started
      using the EDAC Quantifier system in our operating rooms at Penn State Hershey
      Children's Hospital. More basic science studies and clinical outcome data are
      needed for further study in minimizing the adverse effects of pediatric CPB
      procedure.

PMID- 18812740
TI  - Pediatric circulatory support: current strategies and future directions.
      Biventricular and univentricular mechanical assistance.
AB  - Mechanical circulatory support is gaining increased recognition as a viable
      treatment option for pediatric patients who suffer from congenital or acquired
      heart disease. Historically, the treatment options have been very limited for
      pediatric patients, but recent technological advances, combined with new research
      into circulatory support devices, are seeking alternative therapeutics options
      for infants and children. We present a review of the technological advances of
      mechanical circulatory support in the pediatric population, including the recent
      emergence of a new class of circulatory support devices for pediatric patients
      with single ventricle physiology. The National Heart, Lung, and Blood Institute
      pediatric circulatory support program is discussed, in addition to the use of
      adult devices in pediatric applications, the Berlin Heart Excor, and several
      other blood pumps in development for bridge-to-transplant and bridge-to-recovery
      support. These devices have the potential to generate a paradigm shift in the
      treatment of the pediatric patients with heart failure--a shift is likely already
      be underway.

PMID- 18812741
TI  - Use of a pulsatile ventricular assist device (Berlin Heart EXCOR) and an
      interventional lung assist device (Novalung) in an animal model.
AB  - Pulsatile ventricular assist devices (VADs) are used in pediatric patients mainly
      as a bridge to heart transplantation. If severe respiratory failure occurs,
      extracorporeal membrane oxygenation (ECMO) is currently the treatment of choice.
      ECMO has the potential for severe complications. Interventional lung assist (iLA)
      devices, e.g., the Novalung, are used in patients with isolated lung failure.
      This study aimed to show the feasibility of the combined use of the EXCOR VAD (10
      ml and 30 ml blood pumps) and the Novalung. There were two separate experiments
      within this study. First, a bench test was carried out to analyze pressure and
      flow through both devices. Second, 10 kg and 30 kg pigs received support with the
      VAD and iLA in series. Pressures and flow were measured systemically before and
      after the iLA. Flow was unaffected by the iLA. The mean arterial pressure was
      reduced (mean of 13 mm Hg) by the iLA. There were no obvious difficulties
      observed within the interaction of VAD and iLA. The combined use of both devices
      is feasible and able to provide sufficient perfusion pressures. Oxygenation and
      CO2 clearance was effectively supported by the iLA. Patients with myocardial and
      respiratory failure may benefit from this setup.

PMID- 18812742
TI  - Gaseous microemboli detection in a simulated pediatric CPB circuit using a novel
      ultrasound system.
AB  - The objective of this study was to evaluate the effect of flow rate and perfusion
      mode on the delivery of gaseous microemboli in a simulated pediatric
      cardiopulmonary bypass (CPB) circuit with an open arterial filter purge line
      using a novel ultrasound detection system. The circuit was primed with 450 ml
      fresh, heparinized bovine blood plus 200 ml Lactated Ringer's solution (total
      volume 650 ml, corrected Hct 25%). After the injection of 5 ml air into the
      venous line, an Emboli Detection and Classification (EDAC) Quantifier (Luna
      Innovations, Inc., Roanoke, VA) was used to simultaneously record microemboli
      counts at postpump, postoxygenator, and postarterial filter sites. Trials were
      conducted at four different flow rates (500, 750, 1,000, 1,250 ml/min) and two
      perfusion modes (pulsatile, nonpulsatile). Microemboli counts uniformly increased
      with increasing pump flow rates. In all trials, the majority of gaseous
      microemboli detected in the simulated pediatric CPB circuit were <20 microm in
      diameter. At the lowest flow rate tested (500 ml/min), all microemboli (>10
      microm) were cleared from the circuit by the oxygenator and arterial filter.
      Clearance efficiency was decreased at higher flow rates (750-1,250 ml/min). Over
      98% of microemboli detected at the postoxygenator site were <40 microm in
      diameter. In general, pulsatile flow delivered more microemboli to the circuit at
      postpump and postoxygenator sites than nonpulsatile flow. The results of this
      study confirmed that entrained air from the venous line could be delivered to the
      systemic circulation (as represented by our pediatric pseudo patient) at flow
      rates from 750 to 1,250 ml/min, despite the presence of an arterial filter and
      open arterial filter purge line. All of the microemboli distal to the arterial
      filter were smaller than the conventional detectable level of 40 microm.

PMID- 18812743
TI  - Development of a miniaturized heart-lung machine for neonates with congenital
      heart defect.
AB  - Predominantly, standard adult heart lung machines are used for pediatric cardiac
      surgery, only with individually downsized components. Downsizing is limited,
      e.g., by the required gas exchange surface. To diminish complications, we
      developed a new miniaturized heart lung machine (MiniHLM) for neonates, with
      significantly reduced priming volume and blood contact surface by integration of
      all major system components in one single device. In particular, a rotary blood
      pump is centrically integrated into the oxygenator and the cardiotomy reservoir
      with integrated heat exchanger is directly connected. Thus, tubing is only
      necessary between patient and MiniHLM. A total priming volume of 102 ml could be
      achieved for the entire extracorporeal circuit (including arterial/venous line),
      in contrast to the currently smallest device on the market with 213 ml. In first
      animal experiments with female New Zealand rabbits, the MiniHLM guaranteed both a
      sufficient gas exchange and an adequate blood flow; 12 rabbits could successfully
      be weaned off after 1 hour of aortic clamp time. The first in vitro and in vivo
      tests confirm the concept of the MiniHLM. Its low priming volume and blood
      contact surface may significantly reduce complications during heart surgery in
      neonates.

PMID- 18812744
TI  - Validation of a rat model of cardiopulmonary bypass with a new miniaturized
      hollow fiber oxygenator.
AB  - Cardiopulmonary bypass (CPB) is an essential component of cardiac surgery, with
      still unknown device/patient interactions. To evaluate the response of CPB to
      hemodynamic, biochemical, inflammatory, as well as thermo-pharmacodynamic
      interactions, a novel miniaturized oxygenator with controlled and standardized
      specifications has been developed together with an improved surgical central
      cannulation technique. A hollow-fiber small priming volume (6.3 ml) oxygenator
      was manufactured according to specifications resulting from engineering, heart
      surgery and perfusion expertise (Dideco-Sorin Group, Italy) with the following
      characteristics: Gas Exchange Surface--450 cm2, and Heat Exchange Surface--16
      cm2. The oxygenator was tested in vitro and in vivo in five anesthetized,
      ventilated, open-chest rats using a miniaturized roller pump. Pressures were
      monitored in the animal before and after the oxygenator. Central venous
      cannulation through the superior vena cava and aortic cannulation through the
      carotid artery were used. In vitro: blood oxygenation increased 10-fold (from
      room air to 100% O2) and PCO2 removal was 2.5-fold. In vivo: CPB was performed
      without blood prime for 90 minutes (no ventilation) maintaining stable
      hemodynamics. A maximal blood flow rate of 124 ml/min/kg was obtained. Arterio
      venous PO2 gradients were 10-fold (O2 100%) with only small variations when
      changing blood flow rates. This new, standardized and miniaturized hollow fiber
      oxygenator, new cannulation technique and CPB circuit achieved optimal gas
      transfer with small asanguinous priming volumes. This study opens new potentials
      for various CPB-related study protocols in the small animal.

PMID- 18812745
TI  - The capability of trapping gaseous microemboli of two pediatric arterial filters
      with pulsatile and nonpulsatile flow in a simulated infant CPB model.
AB  - The study objective was to test the capability of Medtronic Affinity and Terumo
      Capiox pediatric arterial filters to trap gaseous microemboli in a simulated
      infant cardiopulmonary bypass (CPB) model. The filters were used in parallel
      pattern. The circuit was primed with lactated ringer's solution (700 ml) and
      postfilter pressure was maintained at 100 mm Hg using a Hoffman clamp. Trials
      were conducted at flow rates ranging from 500 to 1,250 ml/min. After introducing
      20 ml air into the venous line via an 18-G needle, 2-minute segments of data were
      recorded. This entire process was repeated 6 times for each unique combination of
      arterial filter, flow rate and perfusion mode, yielding a total of 96
      experiments. More than 80% of gaseous microemboli were trapped by the two
      pediatric arterial filters. With increased flow rates and pulsatile mode, more
      gaseous microemboli passed through the arterial filters. There were no
      differences in terms of the percentage of gaseous microemboli trapped and
      pressure drops between Medtronic Affinity and Terumo Capiox pediatric arterial
      filters. Results demonstrated that Medtronic Affinity and Terumo Capiox pediatric
      arterial filters could trap the majority of gaseous microemboli in this
      particular setting of an open arterial filter purge line in a simulated infant
      CPB circuit with pulsatile and nonpulsatile flow.

PMID- 18812746
TI  - A novel, low cost, disposable, pediatric pulsatile rotary ventricular pump for
      cardiac surgery that provides a physiological flow pattern.
AB  - Research is underway to develop a novel, low cost, disposable pediatric pulsatile
      rotary ventricular pump (PRVP) for cardiac surgery that provides a physiological
      flow pattern. This is believed to offer reduced morbidity and risk exposure
      within this population. The PRVP will have a durable design suitable for use in
      short- to mid-length prolonged support after surgery without changing pumps. The
      design is based on proprietary MC3 technology which provides variable pumping
      volume per stroke, thereby allowing the pump to respond to hemodynamic status
      changes of the patient. The novel pump design also possesses safety advantages
      that prevent retrograde flow, and maintain safe circuit pressures upon occlusion
      of the inlet and outlet tubing. The design is ideal for simple, safe and natural
      flow support. Computational methods have been developed that predict output for
      pump chambers of varying geometry. A scaled chamber and pump head (diameter = 4
      in) were prototyped to demonstrate target performance for pediatrics (2 L/min at
      100 rpm). A novel means of creating a pulsatile flow and pressure output at
      constant RPM was developed and demonstrated to create significant surplus
      hydraulic energy (>10%) in a simplified mock patient circuit.

PMID- 18812747
TI  - A hemodynamic evaluation of the Medos Deltastream DP1 rotary pump and Jostra HL
      20 roller pump under pulsatile and nonpulsatile perfusion in an infant
      cardiopulmonary bypass model--a pilot study.
AB  - This study aims to compare the Jostra HL-20 roller pump to the Medos DeltaStream
      DP1 rotary pump in terms of pressure and flow waveforms, as well as calculated
      energies based on pressure/flow relationships, in a simulated pediatric
      cardiopulmonary perfusion system. The flow rate was set at 1,000 ml/min for each
      pump, under both pulsatile and nonpulsatile perfusion modes. Mean arterial
      pressure (MAP) was maintained at 40 mm Hg. Pressure and flow measurements and
      waveforms were recorded at precannula site in the bypass circuit. Blood analog
      test fluid was used to simulate blood properties. A total of 24 experiments were
      performed (n = 12 nonpulsatile and n = 12 pulsatile). A significant increase in
      surplus hemodynamic energy (SHE) was observed in both pumps under pulsatile
      perfusion. In contrast, nonpulsatile perfusion generated very little SHE in the
      Jostra roller pump, whereas no SHE was generated in the Medos rotary pump.
      However, under pulsatile perfusion, the Medos rotary pump generated more than
      twice the amount of SHE or "extra" energy than the Jostra roller pump. The total
      hemodynamic energy was also significantly higher in the Medos rotary pump than
      the Jostra roller pump, under pulsatile perfusion. This pilot study suggests that
      the Medos DeltaStream DP1 rotary pump may produce greater hemodynamic energy
      levels and higher quality physiologic pressure/flow waveforms than the Jostra
      roller pump. Further investigation of the Medos DeltaStream DP1 rotary pump is
      necessary to evaluate hemodynamic energy generation under various pump settings,
      in contrast to different flow rates.

PMID- 18812748
TI  - The effects of vasopressor and vasodilator on hemodynamic energy in terms of
      surplus hemodynamic energy.
AB  - In a previous study, we reported that inotropic agents affect the hemodynamic
      energy, which can be measured using the energy equivalent pressure (EEP) and
      surplus hemodynamic energy (SHE). However, there has been no study about the
      effect of vasopressors and vasodilators on EEP and SHE. Thus, we investigated the
      change in the hemodynamic energy induced by phenylephrine, nitroprusside,
      norepinephrine, and milrinone in terms of the EEP and SHE. Phenylephrine (1, 3
      microg/kg/min), nitroprusside (0.5, 1 microg/kg/min), norepinephrine (0.1, 0.25
      microg/kg/min), and milrinone (bolus 50 microg/kg, followed by 0.5, 0.7
      microg/kg/min) were infused into 13 anesthetized dogs. The hemodynamic
      parameters, mean arterial pressure (MAP), and flow were recorded in the
      descending thoracic aorta, and EEP and SHE were calculated. MAP, EEP, and SHE
      increased significantly with phenylephrine administration. However, the flow in
      the descending aorta decreased significantly (p < 0.05). Norepinephrine also
      significantly increased MAP, EEP, and SHE (p < 0.05 in all cases). The MAP, EEP,
      and SHE significantly decreased after nitroprusside infusion (p < 0.05), whereas
      milrinone did not have an effect on MAP, EEP, or SHE. In conclusion, vasopressors
      were found to increase EEP and SHE, while a vasodilator decreased EEP and SHE.

PMID- 18812749
TI  - Comparison of two different blood pumps on delivery of gaseous microemboli during
      pulsatile and nonpulsatile perfusion in a simulated infant CPB model.
AB  - The purpose of this study was to compare two different blood pumps (Jostra roller
      pump vs. Medos deltastream DP1 rotary pump) on delivery of gaseous microemboli
      during pulsatile and nonpulsatile perfusion in a simulated infant cardiopulmonary
      bypass (CPB) model. The Jostra and Medos pump were used in parallel pattern. The
      circuit was primed with lactated ringer's solution (700 ml) and the postfilter
      pressure was maintained at 100 mm Hg. Three transducers (postpump, postoxygenator
      and postfilter sites) of the Emboli Detection and Classification (EDAC)
      Quantifier were inserted into the CPB circuit to detect and classify gaseous
      microemboli. Trials were conducted at flow rates ranging from 500 to 1250 ml/min
      (250 ml/min increments). The arterial filter purge line was kept open during all
      trials. After injecting 20 ml air into the venous line, 2-minute segments of data
      were recorded simultaneously through three transducers. This entire process was
      repeated six times for each unique combination of blood pump, flow rate and
      perfusion mode, yielding a total of 96 experiments. Independent of perfusion mode
      and flow rate, Medos pump delivered less gaseous microemboli than Jostra pump at
      the postpump site, but only at 1,250 ml/min of pump flow rate the differences
      reached statistical significance (p < 0.01). There was no difference in delivery
      at the postfilter site. Compared with nonpulsatile flow, pulsatile flow
      transferred significantly more gaseous microemboli at the postpump site at 1,250
      ml/min of pump flow rate in both groups (p < 0.01). The majority of gaseous
      microemboli were trapped by the membrane oxygenator. The results of this study
      confirm that rotary pump could deliver less gaseous microemboli than roller pump
      at the postpump site when a fixed volume air was introduced into the venous line.
      Pulsatile flow could transfer more gaseous microemboli at the postpump site, no
      matter which blood pump was used. Only few gaseous microemboli appeared at the
      postfilter site at high flow rates with an open arterial filter purge line.

PMID- 18812750
TI  - Initial experience with the TandemHeart circulatory support system in children.
AB  - Options for mechanical ventricular assistance in pediatric patients are limited.
      Extracorporeal membrane oxygenation is used in most cases for short-term support.
      The TandemHeart circulatory support system is an established device that is used
      in adult patients to provide short-term ventricular support. In this article, we
      report three children in whom a TandemHeart ventricular assist device was used
      for right ventricular support, two after heart transplantation and another for
      failed Fontan physiology. Herein, we report the novel application of this
      technology to pediatric patients, and we discuss the lessons learned from its
      utilization.

PMID- 18812751
TI  - Management of a pediatric patient on the Berlin Heart Excor ventricular assist
      device with argatroban after heparin-induced thrombocytopenia.
AB  - We report a 15-year-old male patient who developed type II heparin-induced
      thrombocytopenia (HIT) after 6 weeks of heparin administration and placement of a
      Berlin Heart Excor left ventricular assist device (LVAD).

PMID- 18812752
TI  - Prolonged but successful weaning from left ventricular assist device after
      cardiac decompensation due to late-recognized coarctation of the aorta in a
      toddler.
AB  - A 2-year-old boy was presented with late-recognized coarctation of the aorta and
      pulmonary hypertension due to left ventricular failure. The coarctation was
      corrected at the day of admission with a good postoperative result. However,
      weaning from the respirator failed despite multiple drug support due to left
      ventricular failure. Consequently, a left ventricular assist device (LVAD) was
      implanted 22 days later. The further course was complicated by systemic
      hypertension and ongoing pulmonary hypertension requiring extensive
      antihypertensive therapy. The first attempt to wean from LVAD failed and the left
      ventricle was left completely unloaded for additional 4 weeks. The second weaning
      attempt, using a very smooth weaning protocol, led to a recovered left ventricle
      and facilitated the removal of the assist device after a total of 120 days. The
      patient was discharged with normal cardiac function, but he still requires
      antihypertensive therapy. We believe that the slow reduction of the LVAD support
      was the key measure that leads to the successful weaning of the patient, thereby
      avoiding heart transplantation.

PMID- 18812753
TI  - Acute lung failure during mechanical circulatory support.
AB  - The use of venoarterial extracorporal membrane oxygenation and ventricular assist
      devices in children with end stage heart failure is well established. The use of
      a bridge-to-bridge strategy leads to excellent survival rates in pediatric
      patients. We present an adolescent, who acquired acute respiratory failure, due
      to possible transfusion related lung injury, and who was successfully treated
      with venovenous extracorporal membrane oxygenation while on ventricular assist
      device support.

PMID- 18812754
TI  - Enteroviral sepsis and ischemic cardiomyopathy in a neonate: case report and
      review of literature.
AB  - Neonatal entero-viral sepsis is a rare but fulminant infection with multisystem
      involvement, often presenting with hepatitis, meningo-encephalitis, disseminated
      intravascular coagulation (DIC), and myocarditis. Neonatal myocarditis often
      proves fatal. We report here a case of neonatal enteroviral myocarditis with
      multisystem organ failure and ischemic cardiomyopathy that was managed medically.

PMID- 18812755
TI  - Reoperations in adults after correction of tetralogy of Fallot.
AB  - Adults with congenital heart diseases are an increasing patient population. Since
      the first successful palliative procedure in 1945 (Blalock and Tausing, JAMA 128:
      189-194, 1945) and first corrective operation in 1955 (Lillehei et al., Ann Surg
      142: 418, 1955) patients with Tetralogy of Fallot, which is the most common
      cyanotic CHD, have had excellent long term results and good quality of life. Over
      the long term, these patients are under risk of sudden death because of
      arrhythmias and congestive heart disease caused by tricuspid regurgitation,
      pulmonary regurgitation, ventricular septal defect, right ventricular outflow
      tract obstruction.

PMID- 18812756
TI  - Dearest cornea.

PMID- 18812757
TI  - Contact lens-induced corneal peripheral swelling differences with extended wear.
AB  - PURPOSE: To compare central and peripheral corneal swelling with high-Dk
      (lotrafilcon A) and low-Dk (etafilcon A) contact lenses (CLs) during extended
      wear (EW). METHODS: Corneal thickness was measured in 5 corneal locations
      (central, superior, inferior, nasal, and temporal) with Orbscan II pachymetry 1
      week before the wearing of CLs and after 1 week of EW. High-Dk (lotrafilcon A)
      and low-Dk (etafilcon A) soft CLs were randomly fitted for EW in the right and
      left eyes of 20 subjects with normal ocular health. Orbscan was also performed
      before CL removal after 3 and 7 days of EW. RESULTS: Lotrafilcon A induced a
      lower percentage of corneal swelling in all 5 corneal locations than etafilcon A
      (P < 0.05, paired t test). Lotrafilcon A swelling percentages were as follows:
      central (1.67% +/- 2.22%), superior (2.04% +/- 3.25%), inferior (1.38% +/-
      1.74%), nasal (1.50% +/- 2.00%), and temporal (1.27% +/- 1.47%). Etafilcon A
      swelling percentages were as follows: central (4.98% +/- 3.07%), superior (6.62%
      +/- 8.39%), inferior (5.24% +/- 5.54%), nasal (3.41% +/- 3.14%), and temporal
      (4.46% +/- 3.32%). Differences between the central and peripheral corneal
      swelling during EW of both types of lenses were not significant (P > 0.05,
      repeated-measures analysis of variance). CONCLUSIONS: Central and peripheral
      corneal thicknesses increase more with etafilcon A than with lotrafilcon A during
      EW, as measured by Orbscan pachymetry.

PMID- 18812758
TI  - Outcomes of penetrating keratoplasty in mentally retarded patients with
      keratoconus.
AB  - PURPOSE: Mentally retarded patients with keratoconus who underwent penetrating
      keratoplasty (PK) were reviewed to determine long-term graft survival outcome.
      METHODS: This longitudinal retrospective study included 20 mentally retarded
      patients who underwent PK at the University Hospital of Alicante during the years
      1978-2007. Variables included donor corneal study, type and level of mental
      retardation, demographic data, age at which PK was performed, preoperative ocular
      and corneal study, surgical technique, histopathologic study, complications,
      immunological graft rejection, mean suture permanency, corneal endothelium study,
      and final anatomic and visual outcome. RESULTS: Thirty-nine penetrating
      keratoplasties were performed on 28 eyes of 20 patients. Mean age at time of
      surgery was 29.6 years (range 17-54 years). Follow-up ranged from 8 to 324
      months, with a mean of 83.93 months. Vernal keratoconjunctivitis, cataract, and
      posterior capsular opacification were the most frequent complications during
      follow-up. Fifteen episodes of immunological graft rejection were registered. At
      the final examination, 23 grafts remain clear and 5 cloudy. Causes of corneal
      opacification were self-trauma, corneal ulceration, and immunological graft
      rejection. Four eyes developed ptisis bulbi. CONCLUSIONS: PK is a safe procedure
      in mild and moderately mentally retarded patients without compulsive ocular
      patterns. In patients with associated eye rubbing or ocular self-trauma, the
      election has to be made individually and carefully assuming an additional risk of
      serious complications. Providing medical education to caregivers is essential for
      the correct management of these patients.

PMID- 18812759
TI  - Use of sealant (HFG) in corneal perforations.
AB  - PURPOSE: To repair corneal perforation using human fibrin glue and determine its
      efficacy. METHODS: A case series study was performed on corneal perforations up
      to 3 mm in diameter who were admitted in Farabi Eye Hospital. Age, visual acuity,
      presence and size of corneal thinning, corneal epithelial defect, size and depth
      of corneal infiltration, site and size of corneal perforation, corneal
      vascularization, anterior chamber depth, and reaction and the etiology of corneal
      perforation were recorded. Then, corneal perforation was sealed using FG and soft
      contact lens, and the patients were followed up for at least 3 months. Healing of
      the corneal perforation with adhesive was considered as a success (the primary
      outcome) and reported. RESULTS: Of 18 patients, 8 were women and 10 men. The mean
      age of the patients was 52 +/- 25.7 years. The size of corneal perforations was
      0.6-3 mm (mean = 1.88 mm). The etiologies of corneal perforation were
      postinfectious in 11 and noninfectious in 7. Fifteen (83.3%) eyes had successful
      healing of corneal perforation after 3 months. All the patients who were failed
      had corneal perforation larger than 2 mm in diameter. The success rate was higher
      in corneal perforation <or=2 mm in diameter. No case developed giant papillary
      conjunctivitis or secondary glaucoma. Only 1 (5.6%) eye showed a significant
      increase in deep corneal vascularization. CONCLUSIONS: FG is effective in the
      closure of corneal perforations up to 2 mm in diameter. Corneal perforation
      larger than 2 mm may not respond well. It provides fast healing with low rate of
      corneal vascularization.

PMID- 18812761
TI  - Prospective clinical evaluation of McCarey-Kaufman and organ culture cornea
      preservation media: 14-year follow-up.
AB  - PURPOSE: To compare the outcome of corneal grafts preserved in McCarey-Kaufman
      (MK) medium versus organ culture after penetrating keratoplasties. METHODS:
      Paired corneas were stored in McCarey medium for 2-44 hours (mean 21 hours) and
      in organ culture (OC) for 144 -240 hours (mean 192 hours). Penetrating
      keratoplasties were performed by 2 surgeons in 2 groups of patients with
      keratoconus, matched for age. Each pair was transplanted by the same surgeon
      using the same technique. Visual acuity, central corneal thickness, and central
      endothelial cell density were assessed at 166 +/- 7.8 months postoperatively.
      RESULTS: Nine pairs of patients were recovered for a long-term follow-up. The
      mean endothelial cell densities for the MK and OC groups were 611 +/- 155 and 683
      +/- 168 cells/mm, respectively, which were not significantly different. A first
      rapid cell loss rate of 2.07% and 2.52% per month and a second slow of 0.78% and
      0.69% per month were observed in the respective groups. Individual values of best
      corrected visual acuity were all the same (value 1.00) for both groups. Corneal
      thicknesses were, respectively, 571 +/- 52 and 540 +/- 35 microm and were
      significantly different (P = 0.013). CONCLUSIONS: After 14 years of penetrating
      keratoplasties performed with corneas stored in MK versus OC, no significant
      differences were observed in visual acuity, endothelial cell density, and cell
      loss. The observed thinner grafts after OC compared with MK could not be
      explained.

PMID- 18812762
TI  - The value-based medicine comparative effectiveness and cost-effectiveness of
      penetrating keratoplasty for keratoconus.
AB  - OBJECTIVE: To perform a base case, comparative effectiveness, and cost
      effectiveness (cost-utility) analysis of penetrating keratoplasty for patients
      with severe keratoconus. METHODS: Visual acuity data were obtained from a large,
      retrospective multicenter study in which patients with keratoconus with less than
      20/40 best corrected visual acuity and/or the inability to wear contact lenses
      underwent penetrating keratoplasty, with an average follow-up of 2.1 years. The
      results were combined with other retrospective studies investigating complication
      rates of penetrating keratoplasty. The data were then incorporated into a cost
      utility model using patient preference-based, time trade-off utilities, computer
      based decision analysis, and a net present value model to account for the time
      value of outcomes and money. The comparative effectiveness of the intervention is
      expressed in quality-of-life gain and QALYs (quality-adjusted life-years), and
      the cost-effectiveness results are expressed in the outcome of $/QALY (dollars
      spent per QALY). RESULTS: Penetrating keratoplasty in 1 eye for patients with
      severe keratoconus results in a comparative effectiveness (value gain) of 16.5%
      improvement in quality of life every day over the 44-year life expectancy of the
      average patient with severe keratoconus. Discounting the total value gain of 5.36
      QALYs at a 3% annual discount rate yields 3.05 QALYs gained. The incremental cost
      for penetrating keratoplasty, including all complications, is $5934 ($5913
      discounted at 3% per year). Thus, the incremental cost-utility (discounted at 3%
      annually) for this intervention is $5913/3.05 QALYs = $1942/QALY. If both eyes
      undergo corneal transplant, the total discounted value gain is 30% and the
      overall cost-utility is $2003. Surgery on the second eye confers a total
      discounted value gain of 2.5 QALYs, yielding a quality-of-life gain of 11.6% and
      a discounted cost-utility of $2238/QALY. CONCLUSIONS: Penetrating keratoplasty
      for patients with severe keratoconus seems to be a comparatively effective and
      cost-effective procedure when compared with other interventions across different
      medical specialties.

PMID- 18812760
TI  - Subconjunctival bevacizumab for corneal neovascularization.
AB  - PURPOSE: To describe whether subconjunctival bevacizumab decreases corneal
      neovascularization in patients with ocular surface inflammatory diseases.
      METHODS: The study is a retrospective case series that includes 8 eyes of 7
      patients with corneal neovascularization. Patients received 1-3 injections of 2.5
      mg subconjunctival bevacizumab. Morphologic changes were assessed clinically by
      the same investigator at each visit. RESULTS: Subconjunctival bevacizumab was
      well-tolerated without obvious corneal side effects. All 8 eyes of the 7 patients
      showed a reduction in the neovascularized area. CONCLUSIONS: Subconjunctival
      bevacizumab may provide an additional strategy in improving vision or improving
      success of corneal grafts in these patients.

PMID- 18812763
TI  - Ahram mineral water-induced sulfate keratopathy: histopathologic, electron
      microscopic, and confocal scan features.
AB  - PURPOSE: To characterize histopathologic, electron microscopic, and confocal scan
      features of Ahram mineral water (AMW)-induced keratopathy in cadaver corneas.
      METHODS: Seven cadaver globes were examined, 5 of which were exposed to AMW from
      the corneal side for different durations (30 seconds and 3, 15, 30, and 60
      minutes) and the other 2 were considered as control. After performing confocal
      scan on each cornea, we excised the corneoscleral rim and sent it for
      histopathologic evaluation. Scanning electron microscopic and transmission
      electron microscopic examinations were performed on the cornea exposed to AMW for
      60 minutes. RESULTS: Depending on the time of exposure, the confocal scan
      features varied from intraepithelial high-contrast deposits to subepithelial
      bulla formation. The histopathologic features ranged from diffuse
      intracytoplasmic sulfur deposits to subepithelial bulla formation. Scanning
      electron microscopic examination disclosed rather diffuse irregular bright
      deposits of high sulfur content over the surface epithelium and together with
      focal cellular destruction and micro-hole formation in the case with 60-minute
      exposure. On transmission electron microscopy, electron-lucent bulky deposits
      were found underneath the basal epithelial cells and between their basement
      membrane and Bowman layer. Confocal scan of the control corneas disclosed
      nonspecific anterior stromal haze and Descemet folds, with no evidence of
      intraepithelial deposits. No pathologic finding was noted on histopathologic
      examination of the control corneas. CONCLUSIONS: AMW induces sulfate keratopathy
      of mainly anterior corneal involvement and with various histopathologic, confocal
      microscopic, and electron microscopic features even with short-time exposure.

PMID- 18812764
TI  - Use of the poisson probability mass function in a retrospective evaluation of the
      worldwide Fusarium keratitis epidemic of 2004-2006.
AB  - PURPOSE: The Poisson distribution can be used to model discrete events that occur
      infrequently in time, and it was applied, retrospectively, to recently reported
      clusters of Fusarium keratitis. METHODS: This distribution was utilized with data
      reported from 6 geographically diverse ophthalmic centers during the worldwide
      Fusarium keratitis epidemic of 2004-2006. The expected numbers of cases,
      determined from published historical data, were compared with the observed and
      probabilities were calculated. The Poisson probabilities were also used to
      determine the numbers of cases in each cluster required to reach statistical
      significance. RESULTS: The probabilities that the numbers of cases observed in
      the various clusters were a chance variation from the expected, and not due to an
      outbreak, were between 3.83 x 10(-5) and 4.72 x 10(-47). The recognition of the
      first 2 or 3 cases in each cluster was sufficient to establish that an outbreak
      was present. CONCLUSIONS: Because these probabilities are all much less than
      0.05, multiple Fusarium keratitis outbreaks have thus been documented. Future use
      of the Poisson distribution may serve as an "early warning system" that a new,
      potentially modifiable, factor may be operating to increase the occurrence of a
      disease above its historic baseline endemic rate.

PMID- 18812765
TI  - Outbreak of contact lens-related Fusarium keratitis in France.
AB  - BACKGROUND/AIMS: In the context of a recent series of Fusarium keratitis cases in
      Singapore and the United States, we describe an outbreak of fungal keratitis
      attributable to Fusarium species among contact lens wearers in France. METHODS:
      Hospital-based case series. All cases of Fusarium keratitis diagnosed in
      Department of Ophthalmology of the Centre Hospitalier National d'Ophtalmologie
      des Quinze-Vingts in Paris were reviewed from January 2004 through November 2006.
      A standardized telephone interview was conducted to obtain additional clinical
      information for research and the analysis of risk factors. RESULTS: During the
      study period, 17 patients (18 affected eyes) were diagnosed with Fusarium
      keratitis. The vast majority (14 patients, 82%) wore contact lenses. Six patients
      (43% of contact lens wearers) reported using ReNu with MoistureLoc. Eight
      patients reported using others brands of contact lens cleaning solution. The
      final best corrected visual acuity ranged from 20/20 to light perception; 5
      patients (29.5%) required emergency therapeutic or tectonic corneal
      transplantation. No specific differences including Fusarium species or severity
      of keratitis were found between keratitis with ReNu MoistureLoc and keratitis
      without ReNu MoistureLoc. CONCLUSIONS: This series reports the first outbreak of
      Fusarium keratitis in Europe. Once again, ReNu with MoistureLoc, a multipurpose
      lens disinfecting solutions seems to be related with Fusarium keratitis.

PMID- 18812766
TI  - Intacs in advanced keratoconus.
AB  - PURPOSE: To evaluate the surgical outcomes of microthin intracorneal ring segment
      (INTACS) implantation in advanced keratoconus. METHODS: INTACS implantation was
      performed in eyes with advanced keratoconus. The main outcome measures were
      uncorrected visual acuity, best spectacle-corrected visual acuity, change in mean
      refractive spherical equivalent (MRSE), and keratometry. RESULTS: Intacs were
      implanted in 14 eyes with advanced keratoconus. At 6 months, uncorrected visual
      acuity improved from 0.05 +/- 0.08 to 0.16 +/- 0.11 (P < 0.05), and best
      spectacle-corrected visual acuity improved from 0.50 +/- 0.23 to 0.67 +/- 0.00 (P
      = 0.01). The spherical refractive error improved from -6.68 D +/- 6.44 to -3.11 D
      +/- 3.08 (P = 0.03), whereas the cylindrical refractive error improved from -4.89
      D +/- 1.91 to -3.64 D +/- 1.27 (P = 0.04). The MRSE reduced from -9.13 D +/- 5.62
      to -4.93 D +/- 3.19 (P = 0.01), and the average keratometry decreased from 53.01
      D +/- 3.70 to 49.42 D +/- 3.79 (P < 0.05). The results were stable from 6 months
      to 1 year. The procedure showed 100% safety, and more than 60% tolerated contact
      lenses. Younger age, male sex, and minimum central pachymetry of more than 400
      microm seemed to be associated with better outcomes. CONCLUSIONS: In this series,
      Intacs provided good results with respect to visual acuity, corneal topography,
      and MRSE in eyes with advanced keratoconus without major complications or the
      need for segment explanation. INTACS is potentially a safe and efficacious
      treatment option in the management of advanced keratoconus.

PMID- 18812767
TI  - Deep anterior lamellar transplant using lyophilized and Optisol corneas in
      patients with keratoconus.
AB  - PURPOSE: Prospective randomized clinical trial to evaluate the efficacy of
      lyophilized corneas for deep anterior lamellar keratoplasty (DALK) in patients
      with keratoconus. METHODS: Ten eyes underwent DALK and received corneas that had
      been lyophilized, and 10 eyes received corneas kept in Optisol. Follow-up
      examinations included measurement of visual acuity (VA; Early Treatment Diabetic
      Retiropathy Study chart), topography, pachymetry, specular microscopy, contrast
      sensitivity, and confocal microscopy. RESULTS: All variables improved similarly
      in both groups, without statistical differences between them, except for the
      uncorrected VA in the sixth postoperative month, which was better in the
      lyophilized group (0.46) compared with the Optisol group (0.70). The best
      spectacle-corrected VA was 0.16 in the lyophilized group and 0.26 in the Optisol
      group. The mean endothelial cell count during the sixth postoperative month was
      2778.5 in the lyophilized group and 2611.5 in the Optisol group. Optisol corneas
      had greater keratocyte density, and the keratocyte density improved in
      lyophilized corneas during follow-up. CONCLUSIONS: Lyophilized corneas can be
      used successfully for DALK to treat keratoconus with results similar to Optisol
      corneas.

PMID- 18812768
TI  - Genetic ablation of CD36 induces age-related corneal neovascularization.
AB  - PURPOSE: Corneal avascularity is tightly regulated by a balance between
      angiogenic and antiangiogenic factors (angiogenic privilege). In the current
      study, we tested the hypothesis that the CD36+/+ antiangiogenic receptor
      contributes toward the maintenance of corneal avascularity. METHODS: Corneas of
      CD36 wild-type (CD36) and knockout (CD36) mice aged 4, 16, 52, and 78 weeks were
      histologically evaluated for corneal haze and neovascularization (NV).
      Quantitative real-time polymerase chain reaction was performed on corneal tissue
      from CD36+/+ and CD36-/- mice aged 4 and 52 weeks to examine the effect of CD36
      deficiency on expression of relevant angiogenic factors. RESULTS: Corneal haze
      and NV were absent in CD36+/+ mice at all ages. Conversely, corneal haze and NV
      were evident at 52 and 78 weeks in CD36-/- mice, and the latter demonstrated a
      significant increase in vessel density at 52 and 78 weeks. Interestingly,
      compared with CD36+/+ mice, in the corneas of 52-week-old CD36-/- mice,
      thrombospondin-1 messenger RNA was repressed, and vascular endothelial growth
      factor A, c-Jun N-terminal kinase-1, and c-Jun levels were robustly upregulated.
      CONCLUSIONS: CD36-/- mice develop corneal NV that increases in severity with age,
      thus accentuating the role of CD36 in preserving corneal avascularity.

PMID- 18812769
TI  - Human cornea before and after refractive surgery using a new device: VCH-1.
AB  - PURPOSE: To test and measure the refractive index (RI) and to estimate the
      equivalent percentage of water content (%WC) of the anterior layers of the human
      cornea before and after excimer laser photoablation using a novel contact device,
      the VCH-1. METHODS: (1) Repeatability was estimated by sequential measurement of
      the RI of 4 separate hydrogel contact lenses on 2 occasions, 5 and 10 minutes
      after insertion. (2) Patients preselected for photorefractive keratectomy, laser
      assisted sub-epithelial keratomileusis, laser assisted in situ keratomileusis,
      and laser assisted in situ keratomileusis with epithelial flap were enrolled. RI
      was measured for (a) corneal epithelium after topical anesthesia, (b) Bowman
      layer where appropriate after either removing epithelium or lifting the
      epithelial flap and remeasured immediately after excimer laser photoablation, and
      (c) midstroma after lifting the flap (created using mechanical microkeratome) and
      immediately after photoablation. RESULTS: (1) Average repeatability of RI
      measurement was +/-0.001 (range 0.000 to +/-0.002). (2) Mean RI (+/-SD) and
      estimated mean %WC of (a) epithelium were 1.382 (0.006) and 75% (n = 8, age 28-63
      years), (b) Bowman layer 1.380 (0.011) and 77% changing to 1.392 (0.010) and 69%
      after photoablation (n = 11, age 26-40 years, P = 0.005), and (c) midstroma 1.369
      (0.007) and 83% changing to 1.385 (0.006) and 74% after photoablation (n = 30,
      age 22-56 years, P < 0.0001). RI of corneal epithelium and Bowman layer was
      significantly greater than that of midstroma before photoablation (P < 0.001).
      CONCLUSIONS: (1) VCH-1 can reliably measure RI to within +/-0.001 units. This is
      equivalent to an error in water content estimation of +/-0.6%. (2) RI and %WC of
      the human cornea are not uniform. Intersubject and intracorneal variations in RI
      and %WC should be considered because these factors will affect optical
      performance of the eye and photoablation increases RI, presumably by way of
      tissue dehydration.

PMID- 18812771
TI  - A case of polymicrobial keratitis violating an intact lens capsule.
AB  - PURPOSE: To report a case of polymicrobial keratitis resistant to topical and
      intraocular antibiotics with recurrence after penetrating keratoplasty. METHODS:
      Case report. RESULTS: We report a case of polymicrobial keratitis caused by
      Phialophora verrucosa, Candida tropicalis, and Propionibacterium acnes. Initial
      treatment included topical vancomycin, tobramycin, amphotericin B, voriconazole,
      and oral fluconazole, as well as subconjunctival amphotericin B. Penetrating
      keratoplasty was performed, and the infection seemed to have resolved until 4
      weeks after keratoplasty. A second penetrating keratoplasty was performed,
      followed by 4 weekly intracameral injections of voriconazole. Two weeks after the
      fourth intracameral injection, the infection manifested as an active anterior
      chamber reaction. The patient's eye was subsequently enucleated. Histopathologic
      evaluation showed penetration of the crystalline lens by fungus at the site of
      synechiae between the intact lens capsule and iris. CONCLUSIONS: To our
      knowledge, this is the first documented case of a polymicrobial keratitis caused
      by a bacterium, yeast, and a fungus. It is the first histopathologic
      demonstration of fungal penetration of intact lens capsule from infected iris.

PMID- 18812772
TI  - Management of acute hydrops with perforation in a patient with keratoconus and
      cone dystrophy: case report and literature review.
AB  - PURPOSE: To describe a patient with cone dystrophy who presented with acute
      hydrops and perforation, leading to the diagnosis of keratoconus. METHODS: Case
      report and literature review. RESULTS: A 21 -year-old male patient with a history
      of cone dystrophy presented with a flat anterior chamber, diffuse corneal stromal
      edema with an intrastromal cleft, and ruptured Descemet membrane, findings
      consistent with acute hydrops with corneal perforation. After bandage contact
      lens placement and instillation of a cycloplegic agent, the anterior chamber
      reformed within 24 hours. Over the next week, conservative management with a
      bandage lens, pressure patching, topical fluoroquinolone antibiotic, and topical
      cycloplegic led to the reformation and maintenance of anterior chamber stability.
      Corneal topography of the unaffected eye showed global corneal thinning and steep
      sim K readings suspicious for early keratoconus. CONCLUSIONS: Although the
      association between keratoconus and cone dystrophy is extremely rare, our
      patient's vision-threatening complication of acute hydrops with corneal
      perforation highlights the importance of corneal evaluation including topography
      in cone dystrophy. Conservative management was successful in the restoration of
      anatomic integrity in this situation.

PMID- 18812770
TI  - Evaluation of endothelial mucin layer thickness after phacoemulsification with
      next generation ophthalmic irrigating solution.
AB  - PURPOSE: To evaluate human corneal endothelial mucin layer thickness and
      ultrastructure after phacoemulsification and irrigation-aspiration with either
      next generation ophthalmic irrigating solution (NGOIS) or BSS PLUS. METHODS:
      Paired human corneas were mounted in an artificial anterior chamber, exposed to 3
      minutes of continuous ultrasound (US) at 80% power using the Alcon SERIES 20000
      LEGACY surgical system (n = 9) or to 2 minutes of pulsed US at 50% power, 50% of
      the time at 20 pps using the Alcon INFINITI Vision System (n = 5), and irrigated
      with 250 mL of either NGOIS or BSS PLUS. A control group of paired corneas did
      not undergo phacoemulsification or irrigation-aspiration (n = 5). Corneas were
      divided and fixed for mucin staining or transmission electron microscopy. Mucin
      layer thickness was measured on the transmission electron microscopy prints.
      RESULTS: The mucin layer thickness in the continuous phaco group was 0.77 +/-
      0.02 microm (mean +/- SE) with NGOIS and 0.51 +/- 0.01 microm with BSS PLUS (t
      test, P < 0.001). The mucin layer thickness in the pulsed phaco group was 0.79 +/
      0.02 microm with NGOIS and 0.54 +/- 0.01 microm with BSS PLUS (P < 0.001). The
      mucin layer thickness in the untreated control group was 0.72 +/- 0.02 microm.
      The endothelial ultrastructure was normal in all corneas. CONCLUSIONS: In this in
      vitro corneal model, NGOIS, due to its lower surface tension and higher
      viscosity, preserved endothelial mucin layer thickness better than BSS PLUS with
      both the INFINITI Vision System (pulsed US) and the LEGACY surgical system
      (continuous US).

PMID- 18812773
TI  - Acanthamoeba keratitis presenting as a plaque.
AB  - PURPOSE: To report a case of Acanthamoeba keratitis clinically presenting with a
      plaque-like lesion typical of fungal keratitis. METHODS: A 55-year-old woman
      presented with a yellow plaque-like lesion on the cornea surrounded by an
      infiltrate. Smears and culture were taken. The plaque was removed and subjected
      to histopathological investigation. RESULTS: Smear, culture, and histopathology
      results confirmed Acanthamoeba (cysts). The patient was treated with intensive
      topical medication. The infection resolved after 8 weeks of treatment.
      CONCLUSIONS: Acanthamoeba infection of cornea may present as a plaque-like
      lesion. In addition to topical medication, plaque removal helps in early
      resolution of the infection.

PMID- 18812774
TI  - Toxic epidermal necrolysis induced by sulfonamide eyedrops.
AB  - PURPOSE: To describe a case of toxic epidermal necrolysis (TEN) triggered by
      sulfonamide eyedrops. METHODS: A 9-year-old white boy with type I diabetes
      developed fever, constitutional symptoms, and a widespread blistering rash within
      hours of beginning a course of sulfonamide eyedrops for conjunctivitis. The
      patient was intubated and treated with broad-spectrum antibiotics and systemic
      and topical corticosteroids. RESULTS: The patient survived and has bilateral
      acuities of 20/30 at 12 months of follow-up. Pathological examination of a skin
      biopsy sample confirmed the diagnosis of TEN. CONCLUSIONS: TEN is a rare but life
      threatening side effect of topical sulfonamide eyedrops.

PMID- 18812775
TI  - Optical coherence tomography and in vivo confocal microscopy features of
      obstetric injury of the cornea.
AB  - We present a case of a 54-year-old man who reported to our department complaining
      of worsening vision and halos in the left eye. Slit-lamp biomicroscopy showed 2
      distinctive oblique vertical lines situated on the posterior surface of the
      cornea. Anterior segment optical coherence tomography (AS-OCT) demonstrated
      bandlike structures protruding from the cornea into the anterior chamber for
      approximately 430 and 100 microm. In vivo confocal microscopy (IVCM) revealed
      stromal edema, low endothelial density, and prominent hyperreflective linear
      structures at the endothelium depth and behind the endothelium. The patient had a
      history of complicated, in-hospital, forceps-assisted delivery. The perinatal
      ophthalmic history was noncontributory. The fellow eye was healthy. We conclude
      that AS-OCT and IVCM are useful in confirming the clinical diagnosis of suspected
      perinatal corneal trauma because of the specific appearance of the Descemet
      membrane hypertrophic ridge in those examinations. There is a good correlation
      between the results of AS-OCT and IVCM.

PMID- 18812776
TI  - Treatment of multidrug-resistant Flavobacterium indologenes keratitis with
      trimethoprim-sulfamethoxazole.
AB  - PURPOSE: To describe the history, clinical presentation, and successful medical
      management of a case of multidrug-resistant Flavobacterium indologenes keratitis.
      METHODS: An 83-year-old pseudophakic female presented with a 2-day history of
      decreased visual acuity, light sensitivity and dull ocular pain in her right eye.
      Two weeks before presentation, the patient had been treated for a red eye with
      combination topical loteprednol etabonate (0.5%) and tobramycin (0.3%) eye drops.
      Corneal scrappings were performed by the referring ophthalmologist, and hourly
      administration of gatifloxacin 0.3% eye drops was started. Evaluation consisted
      of slit lamp examination, organism identification, and antibiotic sensitivity
      testing. RESULTS: Examination of the right eye revealed a central 5-mm X 2-mm
      anterior stromal infiltrate with an overlying epithelial defect. Gatifloxacin
      0.3% eye drops were stopped, and hourly topical fortified vancomycin (50 mg/mL)
      and ceftazidime (50 mg/mL) eye drops were instituted. Oxidase-positive gram
      negative bacilli were identified in the thioglycollate broth on day 3, and
      therefore, vancomycin was discontinued and hourly ciprofloxacin 0.3% eye drops
      were added to the regimen. The cultures ultimately grew F. indologenes, which was
      highly resistant to all antibiotics tested except for trimethoprim
      sulfamethoxazole. Accordingly, ciprofloxacin 0.3% and ceftazidime were
      discontinued. The patient was started on hourly topical trimethoprim (16
      mg/mL)/sulfamethoxazole (80 mg/mL) eye drops, resulting in clinical control of
      the infection over a period of 1 month. CONCLUSIONS: Flavobacterium indologenes
      keratitis can be resistant to treatment with many medications, and antibiotic
      susceptibility profile testing in these cases may provide crucial information to
      help eradicate the infection.

PMID- 18812777
TI  - Successful medical treatment of a case of Paecilomyces lilacinus keratitis.
AB  - PURPOSE: To report a successful medical treatment of a case of keratitis caused
      by Paecilomyces lilacinus. METHODS: A 68-year-old woman developed an infection of
      the left cornea after minor trauma. The causative organism was found to be a
      particularly virulent organism, P. lilacinus. The patient was initially treated
      with natamycin topically and itraconazole orally, but the organism was resistant
      and failed to respond. She was then switched to topical voriconazole and oral
      terbinafine. RESULTS: The patient was successfully treated with these medications
      without surgical intervention, an unusual outcome for this organism. CONCLUSIONS:
      If one encounters a case of fungal keratitis that fails to respond to the more
      commonly used agents, one should suspect a resistant organism such as
      Paecilomyces and should switch to voriconazole and/or terbinafine both topically
      and orally.

PMID- 18812778
TI  - Penetrating keratoplasty for the exciting eye in sympathetic ophthalmia.
AB  - PURPOSE: We report a case of sympathetic ophthalmitis where we performed
      penetrating keratoplasty on the exciting eye many years after the initial injury.
      METHODS: Case report. RESULTS: After penetrating keratoplasty, the patient
      achieved vision of 3/60 from preoperative perception of light. CONCLUSIONS: Our
      experience shows that penetrating keratoplasty can restore useful vision in the
      previously injured exciting eye in sympathetic ophthalmitis. This case highlights
      a unique example where the inciting eye has ultimately become the eye with the
      better vision as the damage was limited.

PMID- 18812779
TI  - Nocardia transvalensis resistant to amikacin: an unusual cause of microbial
      keratitis.
AB  - PURPOSE: To report a case of microbial keratitis caused by Nocardia transvalensis
      with resistance to amikacin. METHODS: Case report. RESULTS: A 51-year-old man was
      referred with a 10-week history of ocular pain, photophobia, redness, and blurred
      vision. At his initial presentation, a corneal foreign body was removed and he
      was diagnosed with anterior uveitis, with commencement of topical corticosteroid
      therapy and ofloxacin. Despite treatment, he experienced ongoing foreign body
      sensation and glare. At presentation to our clinic, a central epithelial defect
      with multiple stromal infiltrates in a wreath pattern was identified and a
      diagnosis of infective keratitis was made. He was initially commenced on topical
      amikacin, oral trimethoprim-sulfamethoxazole, and oral voriconazole. Corneal
      scraping confirmed Nocardia species. Microbiological culture revealed N.
      transvalensis as the causative organism, with resistance to several antibiotics,
      including amikacin. Clinically, there was only partial response of the keratitis
      to initial therapy. Treatment was changed to oral trimethoprim-sulfamethoxazole
      and topical ciprofloxacin, with eventual clinical improvement. CONCLUSIONS: This
      is the first reported case of N. transvalensis keratitis. In patients with
      Nocardia keratitis and only partial response to amikacin treatment, this isolate
      should be considered as it is resistant to aminoglycoside antibiotics.

PMID- 18812780
TI  - Intraocular lens power calculation after automated lamellar keratoplasty for high
      myopia.
AB  - PURPOSE: To report intraocular lens (IOL) power calculation in 2 eyes that were
      highly undercorrected by previous myopic automated lamellar keratoplasty (ALK).
      METHODS: A 35-year-old man underwent bilateral myopic ALK, which caused high
      residual myopia (-9.0 -4.0 x 171 and -9.5 -4.5 x 74). The patient then underwent
      cataract surgery with IOL implantation for cataract development. The double-K
      clinical history method was utilized, and satisfactory IOL power prediction
      results were obtained. Two no-history IOL power calculation methods (Rosa
      correcting factor method and Ferrara theoretical variable refractive index
      method), which involved axial length-dependent modification of the keratometer
      measured corneal radius, and 1 no-history IOL power calculation method (Shammas'
      method), which involved axial length-independent modification of the keratometer
      measured corneal power, were tested on these 2 eyes. RESULTS: In both eyes, the
      double-K SRK-T clinical history method gave small IOL prediction errors (-0.66
      and -0.81 D). The Shammas' no-history method gave a slightly higher IOL
      prediction error in the right eye (-1.67 D) and a small IOL prediction error in
      the left eye (-0.74 D). Unacceptable IOL power prediction errors would have
      resulted if Rosa's correcting factor method (-8.07 and -8.35 D) or Ferrara's
      theoretical variable refractive index method (-17.56 and -18.51 D) had been
      applied. When we utilized Rosa's method for the IOL power calculation by assuming
      that the previous ALK had fully corrected the refractive error, the predicted IOL
      powers were very close to the benchmark IOL powers (IOL power prediction errors:
      1.16 and 0.37 D). When we utilized Ferrara's method with the same assumption, the
      IOL power prediction errors remained high (-6.32 and -7.16 D). CONCLUSIONS: For
      patients who have had previous myopic ALK (and whose eyes are highly
      undercorrected) and who require cataract surgery and for whom the pre-ALK history
      is available, the double-K method appears to yield excellent predictive results.
      However, if the pre-ALK history is not available, the Shammas' no-history method
      appears to yield better results than the Rosa's or the Ferrara's method. High
      undercorrection by the previous ALK might have been one of the major reasons why
      Rosa's method resulted in a high IOL prediction error in these 2 eyes. The cause
      for the marked IOL prediction error by Ferrara's method in this case, however,
      remains to be determined.

PMID- 18812781
TI  - Combined use of superficial keratectomy and subconjunctival bevacizumab injection
      for corneal neovascularization.
AB  - PURPOSE: To report the effect of superficial keratectomy combined with
      subconjunctival bevacizumab injection in 2 cases of corneal neovascularization
      (NV). METHODS: An interventional case series was undertaken on 2 patients with
      corneal NV: 1 due to sclerokeratitis secondary to rheumatoid arthritis and the
      other due to Terrien marginal degeneration. Both patients underwent superficial
      keratectomy combined with subconjunctival bevacizumab injection (2.5 mg/0.1 mL).
      RESULTS: Corneal NV regressed with the surgical removal and showed no signs of
      recurrence after 3 months of follow-up. Both patients reported dramatic
      subjective improvement in their vision within 1-2 weeks. Best corrected visual
      acuity improved in 1 patient. CONCLUSION: The combination of superficial
      keratectomy with subconjunctival injection of bevacizumab may offer a new
      strategy for the treatment of superficial corneal NV.

PMID- 18812782
TI  - Ocular complications in 2 cases with porphyria.
AB  - PURPOSE: We aimed to report our observation regarding the long-term follow-up
      results of 2 cases with similar ophthalmic manifestations of 2 different
      porphyrias, congenital erythropoietic porphyria (CEP), and porphyria cutanea
      tarda (PCT). METHODS: Both patients presented with ocular pain and photophobia in
      both eyes. The patient with CEP had a scleral necrosis of 3 mm in diameter at the
      lateral limbus of the right eye and medial limbus of the left eye, accompanied
      with cicatricial ectropion and lid swelling OU. The patient with PCT had scleral
      necrosis in the interpalpebral area nasally, OU. RESULTS: Both patients were
      followed-up for 4 years. The patients received intensive topical lubrication and
      topical and oral immune-suppressive medication. They underwent amniotic membrane
      grafting, when required, and were advised to wear UV glasses. The case with PCT
      followed a more salient course and remained symptom free until the end of the
      follow-up period. In contrast, the patient with CEP developed further scleral
      necrosis, despite the treatment and evisceration surgery were inevitable owing to
      endophthalmitis unresponsive to the treatment. CONCLUSIONS: Ocular complications
      are rarely reported in porphyrias, and the studies on the long-term follow-up
      results are fewer. Despite careful follow-up and intensive treatment, scleral
      necrosis can be progressive and results in the loss of vision or even the loss of
      eye. Further studies regarding the care of patients with porphyrias are required
      to more effectively treat these rare ophthalmic conditions.

PMID- 18812784
TI  - Autologous serum eye drops for treating persistent corneal epithelial defect
      after vitreoretinal surgery.

PMID- 18812785
TI  - Suture-pull technique for insertion of donor lenticule in endothelial
      keratoplasty.

PMID- 18812787
TI  - Optical coherence tomography of Descemet membrane separation by the big bubble
      technique.

PMID- 18812789
TI  - Deep lamellar keratoplasty in keratoconus with healed hydrops.

PMID- 18812792
TI  - Acute respiratory distress syndrome: time to entertain a change but not to make
      one.

PMID- 18812793
TI  - Sepsis (mis) management: the hazards of a faith-based approach.

PMID- 18812794
TI  - Unhappy acute lung injury survivors: the case of hypoglycemicly-induced
      depressive symptoms.

PMID- 18812795
TI  - More evidence that timing matters in the treatment of patients with sepsis.

PMID- 18812796
TI  - Have your cake and eat it? Insulin strengthens the stunned heart.

PMID- 18812797
TI  - Children of the intensive care unit.

PMID- 18812798
TI  - Peer networks and the pursuit of excellence in critical care.

PMID- 18812799
TI  - Noninvasive ventilation: trying to minimize harm?

PMID- 18812800
TI  - End-stage renal disease and intensive care unit prognosis: are current tools good
      enough?

PMID- 18812801
TI  - Case mix as the determinant of outcomes: the devil is in the details.

PMID- 18812802
TI  - One for all, and all for one? The globalization of critical care.

PMID- 18812803
TI  - Myosin light chain kinase gene and acute lung injury in trauma and sepsis:
      opposite effects but confirmatory.

PMID- 18812804
TI  - The intensive care experience: what really matters?

PMID- 18812805
TI  - Using pulse pressure variation in patients with acute respiratory distress
      syndrome.

PMID- 18812806
TI  - Combining audiovisual feedback and debriefing: learning or just imitating?

PMID- 18812807
TI  - Benefits of hydroxyethyl starch: lost in translation?

PMID- 18812808
TI  - Even in trauma, time is brain.

PMID- 18812809
TI  - Nonischemic energy metabolic crisis in acute brain injury.

PMID- 18812810
TI  - Pediatric intensive care unit outcome following pediatric hematopoietic stem cell
      transplantation: quo vadis?

PMID- 18812811
TI  - Platelets, von Willebrand factor, a disintegrin and metalloproteinase with
      thrombospondin motifs-13, plasma exchange and multiple organ failure: old
      problem, new approach.

PMID- 18812812
TI  - Rigorous genotype-phenotype association research depends on scientific rigor at
      multiple scales of investigation.

PMID- 18812813
TI  - Link between ADAMTS-13 and troponin levels?

PMID- 18812815
TI  - Effects of vasopressin on renal function in children with severe forms of shock.

PMID- 18812817
TI  - Respite for the critical care workforce crisis.

PMID- 18812819
TI  - Barriers to effective communication in developing world intensive care units.

PMID- 18812820
TI  - Sleep and recovery from critical illness and injury: a review of theory, current
      practice, and future directions.

PMID- 18812822
TI  - Neurointensivists: part of the problem or part of the solution?

PMID- 18812826
TI  - Physicians and sleep deprivation.

PMID- 18812827
TI  - The dual role of the orexin/hypocretin system in modulating wakefulness and
      respiratory drive.
AB  - PURPOSE OF REVIEW: Today, numerous studies show that orexin peptides act as
      regulators of many functions including the control of sleep-wake states,
      breathing, and central chemosensitivity. However, little is known on neuronal
      mechanisms by which orexin regulates breathing in a state-dependent manner. This
      review summarizes recent data on the control of neuronal circuits by orexin, with
      a special emphasis on breathing, central chemosensitivity, and obstructive sleep
      apneas. RECENT FINDINGS: Activity of hypothalamic orexinergic neurons is
      subjected to maturation and is mandatory to maintain long bouts of wakefulness in
      adults. At wake onset, this activity progressively builds up as a result of
      synaptic interactions and reinforces the awake state. Orexin deficiency
      attenuates the hypercapnic reflex only during wakefulness and is correlated with
      an increase in sleep apneas. Intrinsic sensitivity to CO2/pH of orexin neurons
      may impact on brainstem chemosensitive neurons, and this effect likely involves
      TWIK (tandem of P domains in a weak inwardly rectifying K+ channel)-related acid
      sensitive K+ (TASK)-like potassium currents. SUMMARY: Orexin signaling is
      directly involved in the control of upper airway patency in particular during
      wakefulness, whereas decreasing activity of orexinergic neurons may contribute to
      upper airway collapse during sleep causing obstructive sleep apnea. Future
      research should focus on the role of orexin in upper airway control, which may
      lead to new clinical strategies for treating breathing disorders associated with
      sleep.

PMID- 18812828
TI  - Upper airway function in the pathogenesis of obstructive sleep apnea: a review of
      the current literature.
AB  - PURPOSE OF REVIEW: Obstructive sleep apnea is an increasingly prevalent disease,
      with a considerable societal burden. The disease is defined by recurrent
      intermittent collapse of the upper airway. Understanding of and treatment for the
      disease is largely confined to relief of the mechanical obstruction of the upper
      airway by application of continuous positive airway pressure, and less commonly
      weight loss or surgery. However, recent work has focused on the function, rather
      than structure alone, of the upper airway. RECENT FINDINGS: The following
      contributors to upper airway structure and function have been studied:
      traditional fixed anatomical abnormalities, dynamic anatomical changes, upper
      airway dilator muscle dysfunction, lung volumes, and instability in control of
      breathing. In each patient with obstructive sleep apnea, the relative
      contribution of each of these components may be quite variable. The studies
      reviewed here describe methods to evaluate these factors, and some attempts at
      treatment. SUMMARY: Ongoing studies are attempting to classify patients on the
      basis of the underlying pathophysiology. This work suggests that obstructive
      sleep apnea is a heterogeneous disease with multiple root causes. Ultimately,
      such a classification may allow more individualized treatment, not only relying
      on mechanical relief of the upper airway obstruction.

PMID- 18812829
TI  - Portable monitoring for the diagnosis of obstructive sleep apnea.
AB  - PURPOSE OF REVIEW: The demand for expedient diagnosis of suspected obstructive
      sleep apnea (OSA) has increased due to improved awareness of sleep disorders.
      Polysomnography (PSG) is the current preferred diagnostic modality but is
      relatively inconvenient, expensive and inefficient. Portable monitoring has been
      developed and is widely used in countries outside the United States as an
      alternative approach. A portable monitor records fewer physiologic variables but
      is typically unattended and can be performed in the home. RECENT FINDINGS:
      Numerous portable monitor studies have been performed over the past two to three
      decades. The US government and medical societies have extensively reviewed this
      literature several times in an attempt to determine if portable monitoring should
      be more broadly used for diagnosing OSA. In March 2008, the US Centers for
      Medicare and Medicaid Services released a statement allowing the use of portable
      monitoring to diagnose OSA and prescribe continuous positive airway pressure.
      This has potentially opened the door for more widespread use of these devices.
      This review will focus on the literature that has examined portable monitoring as
      a diagnostic tool for OSA. SUMMARY: It is anticipated that portable monitoring as
      a diagnostic modality for OSA will be used more frequently in the United States
      following the Centers for Medicare and Medicaid Services ruling. Physicians and
      others considering the use of portable monitors should thoroughly understand the
      advantages and limitations of this technology.

PMID- 18812830
TI  - The Sleep Heart Health Study: a progress report.
AB  - PURPOSE OF REVIEW: The Sleep Heart Health Study began in 1994 as a prospective
      cohort study of cardiovascular disease. The results of longitudinal analysis are
      not yet available, but numerous analyses of cross-sectional data have been
      published. This review provides an overview of study results so far. RECENT
      FINDINGS: Recent findings covered in this review include a methodological study
      supporting the choice of a 4% oxyhemoglobin desaturation criterion for
      identification of hypopneas; evidence that sleepiness may modify the association
      of sleep apnea with hypertension; the association of sleep apnea with increased
      left ventricular mass in a pattern suggesting predominantly eccentric left
      ventricular hypertrophy; the association of restless legs syndrome with an
      increase in prevalent cardiovascular disease; and the results of a genome-wide
      association study of sleep and circadian phenotypes. SUMMARY: Although designed
      as a prospective cohort study, analysis of cross-sectional data from the Sleep
      Heart Health Study has contributed numerous insights to the field of sleep
      medicine.

PMID- 18812831
TI  - Sleep disorders and end-stage renal disease.
AB  - PURPOSE OF REVIEW: To provide an update on the prevalence and clinical importance
      of sleep disorders in patients with end-stage renal disease (ESRD) and to
      highlight recent findings on their pathogenesis and treatment. RECENT FINDINGS:
      Although poor sleep quality is common in patients with ESRD, it is
      underrecognized. In addition to causing impaired quality of life, poor sleep is
      associated with increased cardiovascular mortality. There is evidence that sleep
      quality may be improved by cognitive-behavioral therapy that may help to reduce
      the frequent use of hypnotic medication. There are differences in the clinical
      presentation of sleep apnea in patients with ESRD compared with patients with
      normal renal function. The pathogenesis of sleep apnea in patients with ESRD
      appears to be related both to increased chemosensitivity, which destabilizes the
      control of breathing, and narrowing of the upper airway, which predisposes to
      closure of the airway during sleep. Although renal transplantation corrects
      periodic leg movements, it does not always correct sleep apnea. SUMMARY: Sleep
      disorders are common in patients with ESRD. Although our understanding of their
      pathogenesis and clinical presentation has grown in recent years, further
      research is required to determine their impact on clinical outcomes in this
      patient population.

PMID- 18812832
TI  - Treatment alternatives for sleep-disordered breathing in the pediatric
      population.
AB  - PURPOSE FOR REVIEW: Childhood sleep-disordered breathing (SDB) is associated with
      a myriad of health problems that underscore the need for early diagnosis and
      treatment. Children with SDB present with behavior problems, deficits of general
      intelligence, learning and memory deficits, evidence of brain neuronal injury,
      increased cardiovascular risk, and poor quality of life. Children are in a rapid
      state of cognitive development; therefore, alterations of health and brain
      function associated with SDB could permanently alter a child's social and
      economic potential, especially if the disorder is not recognized early in life or
      is treated inadequately. RECENT FINDINGS: There is evidence that the majority of
      the problems associated with SDB improve with treatment. Treatment strategies are
      now being aimed at mechanisms underlying the disorder. There are multiple
      treatment options available to children; some are novel, with pending treatments
      on the horizon that may replace age-old therapies such as adenotonsillectomy or
      nasal positive pressure. SUMMARY: It is imperative that healthcare workers
      actively seek out signs and symptoms of SDB in patients to improve early
      detection and treatment for prevention of long-term morbidity.

PMID- 18812834
TI  - Ibuprofen therapy for cystic fibrosis lung disease: revisited.
AB  - PURPOSE OF REVIEW: Ibuprofen was first advocated as a chronic therapy for cystic
      fibrosis lung disease in 1995, following a favorable report of a 4-year
      controlled trial. However, clinical use has been limited primarily by the concern
      about adverse effects. Additional clinical studies were advocated to better
      assess the risk-benefit profile. The results of several studies have been
      published within the last couple of years. RECENT FINDINGS: Results from a 2-year
      multicenter trial were consistent with the 4-year trial in demonstrating a
      beneficial effect of ibuprofen on lung function in children with mild to moderate
      lung disease. The drug also showed a favorable safety profile. Results from an
      analysis of observational data from the Cystic Fibrosis Foundation Patient
      Registry collected over 7 years revealed that 'real world' clinical use of
      ibuprofen was also associated with a beneficial effect. The occurrence of
      gastrointestinal bleeding was higher in those treated with ibuprofen, but the
      incidence was very low. SUMMARY: Ibuprofen has now been shown in two long-term
      clinical trials to slow disease progression, with real-world clinical use
      supporting its effectiveness. Although the therapy is not without adverse
      effects, the benefits appear to outweigh the risks.

PMID- 18812833
TI  - Update on gene modifiers in cystic fibrosis.
AB  - PURPOSE OF REVIEW: Cystic fibrosis (CF) is a common, life-limiting monogenic
      disease, which typically manifests as progressive bronchiectasis, exocrine
      pancreatic dysfunction, and recurrent sinopulmonary infections. Although the gene
      responsible for CF (CFTR) was described in 1989, it has become increasingly
      evident that modifier genes and environmental factors play substantial roles in
      determining the severity of disease, particularly lung disease. Identifying these
      factors is crucial in devising therapies and other interventions to decrease the
      morbidity and mortality associated with this disorder. RECENT FINDINGS: Although
      many genes have been proposed as potential modifiers of CF, only a handful have
      withstood the test of replication. Several of the replicated findings reveal that
      genes affecting inflammation and infection response play a key role in modifying
      CF lung disease severity. Interactions between CFTR genotype, modifier genes, and
      environmental factors have been documented to influence lung function measures
      and infection status in CF patients. SUMMARY: Several genes have been
      demonstrated to affect disease severity in CF. Furthermore, it is likely that
      gene-gene and gene-environment interactions can explain a substantial portion of
      the variation of lung disease. Ongoing genome-wide studies are likely to identify
      novel genetic modifiers. Continued exploration of the role of genetic and
      nongenetic modifiers of CF is likely to yield new options for combating this
      debilitating disease.

PMID- 18812835
TI  - Update on fat-soluble vitamins in cystic fibrosis.
AB  - PURPOSE OF REVIEW: We review and critique recent scientific advances in the
      understanding of fat-soluble vitamins and the care of people with cystic
      fibrosis. RECENT FINDINGS: A shift in the conceptual approach to fat-soluble
      vitamin status has occurred. Vitamin status in cystic fibrosis had previously
      been discussed in terms of sufficiency versus insufficiency as compared with
      healthy populations. The discussion of vitamin status has now shifted to that of
      suboptimal versus optimal with respect to health outcomes. This is best
      illustrated by advances in the study of vitamin D. Newer metabolic and
      immunological roles and biomarkers have been identified. With supplementation of
      water-miscible formulations of preformed vitamin A, increased serum retinol has
      been observed, and may increase the risk for toxicity. SUMMARY: A paradigm shift
      has occurred in defining fat-soluble vitamin status by utilizing different
      biomarkers and associations with health outcomes. Identification of additional
      biomarkers, redefining definitions of adequacy, optimal surveillance for toxicity
      as well as adequacy is needed for care of patients with cystic fibrosis.

PMID- 18812836
TI  - Prevalence and impact of depression in cystic fibrosis.
AB  - PURPOSE OF REVIEW: Numerous studies have demonstrated that patients with chronic
      illnesses are at an increased risk for depression, with serious direct and
      indirect consequences for health outcomes. The few studies examining rates of
      depression in patients with cystic fibrosis (CF) or parent caregivers have found
      clinically significant elevations. Given the importance of identifying and
      treating symptoms of depression, the purpose of this review was to highlight
      recent data on the prevalence and impact of depression in CF patients and to
      propose recommendations for screening and treatment. RECENT FINDINGS: Recent
      studies in CF have revealed higher rates of depression in children, adolescents,
      adults, and parent caregivers than in healthy populations. Evidence also suggests
      that depression has negative effects on treatment adherence, family functioning,
      and health-related quality of life. Briefly, well validated screening tools for
      depression are available but are not currently utilized in routine CF care.
      Effective psychological and pharmacological interventions are available to treat
      depression, but have not yet been evaluated in patients with CF. SUMMARY:
      Depression is a significant risk factor for the effective management of CF.
      Screening and treatment of depression in CF centers is recommended and holds
      promise for improving social, emotional, and physical health outcomes.

PMID- 18812837
TI  - Selection of cystic fibrosis patients for lung transplantation.
AB  - PURPOSE OF REVIEW: To update readers on current recommendations for timing of
      lung transplantation in individuals with end-stage cystic fibrosis lung disease
      and on the rationale behind listing decisions. RECENT FINDINGS: Guidelines for
      the referral and selection of patients suitable for lung transplantation were
      recently updated by the pulmonary council of the International Society for Heart
      and Lung Transplantation. However, an analysis published in 2007 has questioned
      whether lung transplantation extends life in children with cystic fibrosis. There
      are some concerns regarding this analysis, and these are discussed in detail.
      Most importantly, the analysis is specific to the United States and predates the
      introduction of the lung allocation score, which has had a marked impact on how
      transplant organs are allocated in this country. SUMMARY: It is likely that lung
      transplantation can extend life in both adults and children with cystic fibrosis,
      provided the procedure is correctly timed. Further development of the lung
      allocation score has the potential to increase the survival benefit from the
      procedure in the United States.

PMID- 18812839
TI  - Bibliography. Current world literature. Sleep and respiratory neurobiology.

PMID- 18812838
TI  - Update on non-cystic fibrosis bronchiectasis.
AB  - PURPOSE OF REVIEW: There is growing awareness in both adult and paediatric
      respiratory clinics regarding the importance of non-cystic fibrosis
      bronchiectasis. There has been debate regarding the requirement for
      investigations to establish an underlying cause of bronchiectasis. Furthermore,
      there has been growing interest in establishing the role of bacteria in disease
      progression. RECENT FINDINGS: Post-infection is no longer the most common cause
      of bronchiectasis in developed countries in children or adults and the importance
      of identifying immunodeficiency has been underlined. Nontuberculous mycobacteria
      are recognized as both causing and complicating non-cystic fibrosis
      bronchiectasis. It has been suggested that infection with Pseudomonas aeruginosa
      may confer a worse prognosis compared with other pathogens but recent
      publications produce conflicting views. There is increasing recognition that
      patients with non-cystic fibrosis bronchiectasis do not necessarily respond to
      cystic fibrosis treatment regimens in the same way as patients with cystic
      fibrosis regimens. SUMMARY: Non-cystic fibrosis bronchiectasis can be approached
      in a systematic fashion to establish the underlying cause and develop treatment
      strategies.

PMID- 18812840
TI  - Stem cells the core of tissue engineering: an advancement in regenerative
      medicine, from flaps to tissue engineering.

PMID- 18812841
TI  - Fetal diagnosis of cleft lip: natural history and outcomes.
AB  - Previous studies have suggested that most fetuses diagnosed prenatally with cleft
      lip have multiple associated anomalies, that fetuses with isolated cleft
      lip/palate are uncommon, and that their ultimate outcome is poor (Lopoo, 1999).
      However, our clinical experience failed to make a similar connection. The purpose
      of this study was to examine the natural history and current outcomes of fetuses
      diagnosed with cleft lip. A retrospective study was performed on all patients
      undergoing fetal ultrasonography over a 7-year period (1993-2001) in a tertiary
      referral center. All patients who had a fetal diagnosis of cleft lip were
      reviewed (N = 57). Fifty-seven fetuses with cleft lip were identified. Forty
      three of 57 patients have complete records. Of these, 18 patients (43%) had
      terminations for associated severe malformations. Three fetuses (7%) had
      intrauterine or neonatal demise. The remainder, 22 fetuses (53%) survived to
      term. Of this group, 18 (82%) of 22 infants were diagnosed postnatally with
      isolated cleft lip/palate and no associated anomalies. Only 4 of 22 had
      associated anomalies. All recorded terminations were performed with known
      karyotyping. We demonstrate that a significant percentage of fetuses diagnosed
      ultrasonographically with cleft lip/palate in our study were isolated and that
      this subset of patients has an excellent prognosis and outcome. This may provide
      further or alter implications for genetic counseling and management.

PMID- 18812842
TI  - Distraction osteogenesis in the management of severe maxillary hypoplasia in
      cleft lip and palate patients.
AB  - The aim of this study was to systematically review literature reporting on the
      use of external distraction osteogenesis (DO) and internal DO in the treatment of
      severe maxillary hypoplasia in cleft and palate patients. Literature research has
      been performed using the PubMed database of the National Library of Medicine and
      National Institutes of Health from 1966 to August 2007. We used cleft lip and
      palate and distraction osteogenesis as key words. Of the 104 articles found, we
      only considered the Anglo-Saxon literature, which reported on the correction of
      the maxillary hypoplasia with DO techniques. A total of 32 studies reported on
      anteroposterior external DO (27 studies on rigid external device and 5 on face
      mask), 17 studies reported on anteroposterior internal DO, and 3 studies reported
      on transverse internal DO have been retained for this review. Despite the
      heterogeneity and methodological limitations of most of the studies, results
      showed that external DO with rigid external device and internal DO resulted to be
      a more reliable and accurate technique than the face mask in the management of
      severe maxillary hypoplasia in patients with cleft lip and palate. The current
      review demonstrated that external and internal DO in the treatment of severe
      maxillary hypoplasia in cleft and palate patients (1) is a reproducible and
      valuable alternative to standard orthognathic surgery procedures, (2) allows for
      a global improvement in facial aesthetic, (3) allows a maxillary correction in
      patients during the period of mixed dentition, and (4) allows either for an
      unchanged or better velopharyngeal function.

PMID- 18812843
TI  - Somatosensory-evoked magnetic fields in examining lip area in speech-disordered
      children.
AB  - Magnetoencephalography (MEG) is a modern neurophysiological method to study brain
      activation after sensory stimulation. We aimed at determining the feasibility of
      MEG and somatosensory-evoked magnetic fields (SEFs) in assessing the lip area in
      speech-disordered children undergoing oral plate therapy (OPTH) to improve their
      articulation. Seven subjects (age range, 6-11 years) participated in the study.
      The speech was perceptually assessed, and the SEFs to tactile stimulation of the
      lip area were recorded before and after OPTH. Two patients did not attend the
      posttreatment MEG recording. Clinical perceptual analysis showed remarkable
      improvement of speech of the studied children after OPTH. Somatosensory-evoked
      magnetic fields were successfully recorded in 4 of these children, but no
      constant changes in the responses were found after the therapy.With this small
      number of patients, the possible modifications in the functioning of the cortical
      somatosensory area of the lip after OPTH remained undetected. The present method
      is, however, technically applicable in studying cortical responses to lip
      stimulation in speech-disordered children. Further studies using stimulation
      inside the mouth may provide more insight to the cortical effects of OPTH.

PMID- 18812844
TI  - Effects of preoperative local ropivacaine infiltration on postoperative pain
      scores in infants and small children undergoing elective cleft palate repair.
AB  - Previous data have shown that preoperative analgesia may reduce postoperative
      analgesic demands. The aim of the current study was to determine if preincisional
      ropivacaine infiltration may reduce postoperative oral pain in infants and small
      children undergoing elective cleft palate patients.Twenty nonsyndromic cleft
      palate patients were randomly divided into 2 groups. Injection with ropivacaine
      hydrochloride, at dose of 0.2 mg/kg, was performed by submucous infiltration of
      the proposed incisional site groups of patients. In control group, no medication
      was given before cleft palate repair under general anesthesia. Postoperative pain
      scores were measured according to Children and Infants Postoperative Pain Scale.
      Heart rate recordings and noninvasive blood pressure measurements were also done
      in all the patients.Measurements of Children and Infants Postoperative Pain Scale
      scores at all the observational postoperative periods showed significantly
      favorable values in ropivacaine group than in control group (P < 0.05). Six
      patients in the control group required rescue analgesia, whereas 2 patients
      required analgesic therapy in the treatment group.Preemptive analgesia using
      ropivacaine may enhance early postoperative comfort by reducing early
      postoperative pain in primary cleft repair.

PMID- 18812845
TI  - Nasomaxillary reconstruction in Binder syndrome: bone versus cartilage grafts. A
      long-term intercenter comparison between Sweden and Mexico.
AB  - Maxillonasal dysplasia is characterized by a concave facial profile and a flat
      nose. The etiology of Binder syndrome is skeletal hypoplasia around the piriform
      aperture and excavations-fossae prenasales, bilaterally in the nasal floor-which
      are pathognomonic. There is no real shortage of the soft tissues. In 2 medical
      centers in Sweden and Mexico, different grafts were used for reconstruction, but
      the focus was similar, filling out the maxilla anterior to the nasal floor and
      supporting the nasal framework to normalize tip projection. The basis for this
      study was to compare the long-term results between bone grafts in Sweden and
      cartilage grafts in Mexico. Sixteen patients from both groups were available for
      long-term follow-up. Simplified digital analysis of anthropometric variables were
      performed in the short-term and long-term follow-ups. The Swedish group had
      primary at the mean age of 21.3 years, whereas mean follow-up period was 16.8
      years later. The Mexican group had primary at the age of 13.6 years, and the
      follow-up period was 8.4 years. Secondary correction was necessary in 25% of the
      patients in the bone graft group (Sweden) and in 19% of patients in the cartilage
      group (Mexico). Bone grafts slightly relapsed in tip projection and remodeled to
      some extent in the nasolabial angle. Cartilage grafts showed stability in the tip
      projection quotients and resulted in a postoperative normalization of the
      nasolabial angle but developed a slight relapse between the short-term and long
      term follow-ups. Both techniques were stable in nose tip-length ratio, and a
      normalization of anthropometric variables was demonstrated in all the long-term
      follow-ups. Both the bone and cartilage graft techniques at the 2 centers
      rendered the intended result of an increased and normalized angle of convexity of
      the face and nasal tip projection. An experience in the properties and behavior
      of either graft is necessary to get a long-term stable outcome.

PMID- 18812846
TI  - Mandibular distraction osteogenesis for Pierre Robin sequence: what percentage of
      neonates need it?
AB  - Neonates with Pierre Robin sequence have respiratory distress caused by
      glossoptosis due to microretrognathia. Numerous therapeutic maneuvers have been
      used to stabilize the upper airway in these patients. The purpose of this study
      is to document the frequency with which each of these maneuvers is used,
      including the newest technique of mandibular distraction osteogenesis, in a
      single hospital with a large obstetrical service (22,646 deliveries between July
      1, 2003, and June 30, 2006).The neonatal intensive care unit records for 3
      consecutive years were reviewed retrospectively to identify all neonates with a
      diagnosis of respiratory distress (40%). Fifteen of these were classified as
      having Pierre Robin sequence, of whom, 9 did not have other craniofacial
      anomalies. The neonates with confounding additional congenital anomalies were
      excluded. The included neonates underwent airway and craniofacial evaluations by
      experienced pediatric otolaryngologists, craniofacial plastic surgeons and,
      occasionally, pediatric pulmonologists. Nonsurgical upper airway stabilization
      was attempted initially for all neonates. Four neonates with isolated Pierre
      Robin sequence could not be stabilized nonsurgically and underwent mandibular
      distraction in lieu of tracheotomy. Two of these subsequently required
      tracheotomy for reasons other than microretrognathia and glossoptosis. The
      remaining 5 Pierre Robin sequence neonates were stabilized without surgery and
      discharged home on room air.The treatment of neonatal upper airway obstruction
      due to Pierre Robin sequence includes both nonsurgical and surgical
      interventions. Use of a therapeutic algorithm can optimize nonsurgical management
      and minimize the need for tracheotomy. Mandibular distraction osteogenesis is an
      effective treatment to avoid tracheotomy in carefully selected Pierre Robin
      sequence neonates.

PMID- 18812847
TI  - Bone morphogenetic protein 2 therapy for craniofacial surgery.
AB  - Between 2 and 10 years of age, the developing craniofacial skeleton poses a
      significant reconstructive challenge. Local autogenous bone is largely
      unavailable, distant bone grafts are fraught with significant morbidity and
      limited yield, and alloplastic materials are incompatible with the growing
      calvarium and facial skeleton. Bone morphogenetic protein (BMP) 2, a member of a
      class of proteins first noticed in the 1960s to promote bone deposition in soft
      tissues, offers a potential solution to the bone shortage historically faced by
      the pediatric craniofacial surgeon. A review of English language literature was
      conducted from the 1960s to the present.Attention was focused on BMP-2's
      osteoinductive mechanism, basic science and translational laboratory findings,
      and multidisciplinary clinical experiences. Bone morphogenetic protein 2 has been
      embraced by spine surgeons, is gaining in popularity for long-bone repair, and is
      making its way into the plastic surgery literature. Bone morphogenetic protein 2
      may provide a basis for an off-the-shelf tissue-engineered bone construct that is
      compatible with the growing craniofacial skeleton while free from the morbidities
      of distant graft harvest. Questions remain, however, regarding the safety and
      efficacy of this compound in the context of pediatric craniofacial surgery. In an
      effort to facilitate the clinician's risk-benefit analysis of this emerging
      technology, we present a primer on the basic science of BMP-2, a discussion of
      possible morbidities associated with its use, a review of laboratory and clinical
      trials with this substance to date, and an analysis of strategies to maximize its
      efficacy in craniofacial surgery.

PMID- 18812848
TI  - Horizontal maxillary osteotomy with interpositional fibula flap.
AB  - Horizontal maxillary osteotomy with an interpositional fibula flap for maxillary
      deficiency offers several advantages over conventional techniques for maxillary
      reconstruction. Maxillary deficiencies in all 3 planes, vertical, anterior
      posterior, and transverse, can be corrected with a long-term stable construct
      while simultaneously restoring bony and soft tissue deficiencies. We conducted a
      retrospective review of patients with maxillary hypoplasia who underwent
      Horizontal maxillary osteotomy with interpositional osteoseptocutaneous fibula
      flaps. Compared with nonvascularized bone grafts, vascularized bone flaps undergo
      less resorption and can be used in poorly vascularized, mechanically unstable,
      irradiated, or scarred wound beds.

PMID- 18812849
TI  - A clinical study on temporomandibular joint ankylosis in children.
AB  - Temporomandibular joint (TMJ) ankylosis is a disabling condition of the
      masticatory system and is most commonly due to trauma, infections, and some
      systemic diseases. Hypomobility affects the surrounding structures as well as the
      joint itself. Ankylosis arising in early childhood usually leads to facial
      asymmetry. Ankylosis in children usually occurs from an intracapsular compression
      fracture or rarely from a suppurative arthritis of middle ear infection.Treatment
      of the ankylosis is probably one of the greatest challenges in TMJ surgery, and
      the treatment of TMJ ankylosis in children is much more challenging than in
      adults because of high recurrence and the probable change in the unpredictable
      growth of the mandible. In treatment of TMJ ankylosis in children, to maintain a
      normal growth and the development of the face is as important as to provide a
      satisfactory mouth opening with free movement of the mandible.A variety of
      techniques and various success rates in the treatment of TMJ ankylosis both in
      adults and in children have been reported. However, no single method has produced
      uniformly successful results. In this study, gap arthroplasty was applied in 6
      patients, and 2 different types of fossa implants were used as interpositional
      material in the other 8 patients, and the results of the treatments have been
      evaluated retrospectively.

PMID- 18812850
TI  - Transnasal endoscopic repair of choanal atresia: results of 13 cases and meta
      analysis.
AB  - Transnasal endoscopic approach for the repair of choanal atresia (CA) has gained
      favor in recent years. However, the studied cohorts are too small to make a
      comprehensive comment on this approach. The aim of this study was to evaluate the
      effects of different techniques, used for the removal of CA under endoscopic
      guidance, on surgical outcome and effectiveness of transnasal endoscopic approach
      in these patients as a whole. We present the results of transnasal endoscopic
      repair of CA in 13 patients and made a meta-analysis of similar studies in the
      literature. Mean success rate with transnasal endoscopic repair was 85.3% in a
      total of 238 cases in 20 studies that met the inclusion criteria. Only the
      history of previous surgery for CA seemed to significantly decrease the
      postoperative success rate (P = 0.029). Rate of revision surgery did not
      significantly differ between mixed, bony, or membranous atresia (P = 0.395).
      Likewise, simple perforation or complete excision of the atretic plate under
      endoscopic view (P = 0.513), use or no use of mucosal flap to seal the denuded
      bone of the choana (P = 0.472), and postoperative stenting or no stenting (P =
      0.252) have proved not to considerably have influence on the surgical outcome.
      Death of perioperative bleeding was the single major complication in 1 case among
      all of the study groups. In conclusion, types of CA, excision method, and
      stenting have no significant effect on surgical outcome of CA. Irrespective of
      the technique used for the excision and the repair of atretic plate, transnasal
      endoscopic approach with higher success rate and minimal postoperative morbidity
      is a good choice for the repair of CA.

PMID- 18812851
TI  - A clinical study on treatment of temporomandibular joint chronic recurrent
      dislocations by a modified eminoplasty technique.
AB  - Various augmentation techniques have been proposed to incarcerate the condyle for
      the treatment of temporomandibular joint chronic recurrent dislocation (CRD).
      Some of them have been used successfully, whereas some of them failed. The
      purpose of this study was to present an alternative eminoplasty technique, more
      specifically an inlay augmentation technique of articular eminence in the
      treatment of temporomandibular joint CRD. Twelve patients, 11 of whom had
      bilateral and the remaining 1 of whom had unilateral CRD, were evaluated. The
      same technique was used in the treatment of all patients. An oblique osteotomy of
      the eminence was carried out. Harvested chin graft was contoured in wedge form
      and inserted tightly into the osteotomy site. The augmentation of the eminence
      was provided by an inlay cortical bone graft without using any of the
      conventional fixation materials used to secure the bone graft. All of the
      symptoms of CRD have disappeared in the postoperative stage. Long-term follow-up
      revealed satisfactory mouth opening and augmentation of the eminence. None of the
      fixation materials such as wire, screw, or miniplate were used to keep the bone
      graft in proper place, and yet, patients had no further episode. It provided
      shorter operating time for surgeon and satisfactory postoperative results.

PMID- 18812852
TI  - Tooth autotransplantation in a free iliac crest graft for prosthetic
      reconstruction.
AB  - This report documents successful tooth autotransplantation to a free iliac crest
      graft in an exemplar case. A 14-year-old male patient was operated thrice with
      increasing amounts of resection for recurrent odontogenic myxoma. When mandibular
      continuity resection finally was performed, a free iliac crest block
      autotransplant was used for reconstruction. Upon metal removal 5 months later, 3
      wisdom teeth with two-thirds complete root development were transplanted to the
      free graft and retained by fixed orthodontic appliances including skeletal
      anchorage with orthodontic microscrews. Tooth graft taking was awaited for 8
      weeks with retention. Following undisturbed healing without occlusal forces, 6
      months of orthodontic treatment intentionally extruded the autotransplanted teeth
      to antagonist contact. The third and most dorsal tooth became mobile after 3
      months and was lost. The surviving 2 teeth were fitted by a prosthetic bridge as
      extrusion into the occlusal plane was not completely successful. This exemplar
      case shows benefit of tooth autotransplants in selected cases of jaw
      reconstruction with distal bone autotransplants as alternative to dental titanium
      implants and suprastructures. Orthodontic microscrews can moreover support tooth
      movement and positioning as anchorage device in altered anatomy.

PMID- 18812853
TI  - Radiation-induced sarcomas of the head and neck.
AB  - The aim of this study was to report our experience on the management of radiation
      induced sarcomas (RISs). A retrospective study from 1994 to 2003 was done at our
      institution reviewing the medical records of 5 patients who had RISs. Five
      patients diagnosed of head and neck cancer received irradiation to treat their
      diseases. Later on, these patients developed new neoplasms in the irradiation
      fields (3 malignant fibrous histiocytoma, 1 osteosarcoma, and 1 angiosarcoma).
      The mean period of latency between irradiation and diagnosis of new tumors was 13
      years. Early symptoms included neck or face swelling, odynophagia, or trigeminal
      hypoesthesia. All of the patients underwent surgical treatment. In 4 cases,
      regional and free flaps for head and neck reconstruction were required. Three
      patients also needed neoadjuvant chemotherapy. In the follow-up, 2 patients are
      alive and free of disease. Wide excision is the treatment of choice for RISs.
      Previous radiation therapy limits the dose that can be administered to the
      involved area, and the response rate to the chemotherapy is always poor.

PMID- 18812854
TI  - Global age-dependent differences in gene expression in response to calvarial
      injury.
AB  - Children less than 2 years of age are capable of healing large calvarial defects,
      whereas adults have been found to lack this endogenous ability. In this study, we
      used microarray analysis to compare genomewide expression patterns during active
      regeneration after injury with calvaria in skeletally immature and mature mice.
      Parietal bone defects were created in 6-day-old (juvenile) and 60-day-old (adult)
      mice using a 4-mm trephine bit (n = 20 mice per age group). The calvarial disc
      was removed, leaving the underlying dura mater intact. Two weeks after injury,
      the region of regeneration with the underlying dura mater was harvested, and RNA
      was extracted for microarray analysis. The 25 most differentially upregulated
      genes in juvenile regenerates compared with adults were listed, as well as
      selected bone-related genes. In addition, QRT-PCR confirmation of specific genes
      was performed for validation. Juvenile regenerates expressed significantly
      greater amounts of BMP-2, -4, -7, as well as FGF-2 and its receptor FGFR-1.
      Various other growth factors were also noted to be upregulated, including IGF-2
      and Ptn. This corresponded with the increased expression of markers for
      osteogenic differentiation of Sparc and Oc. Markers of osteoclast activity, Acp5,
      Ctsk, and Mmp2, were noted to be greater in juvenile regenerates compared with
      adults. The observation of Mmp14 upregulation, however, highlights the importance
      of balanced osteoclast-mediated bone resorption for ultimate healing. The 2 most
      differentially regulated genes, transthyretin (Ttr) and prostaglandin D2 synthase
      (Ptgds), highlight the potential role of retinoic acid signaling and the
      prostaglandin axis on skeletal regeneration. These findings underscore the
      multitude of biomolecular mechanisms at play, allowing juvenile calvaria to heal
      after injury. The identification of various growth factors and cytokines involved
      also suggests novel therapeutic strategies for tissue-engineering purposes.

PMID- 18812855
TI  - Maxillary growth impairment in cleft lip and palate patients: a simplified
      approach in the search for a cause.
AB  - No true consensus exists regarding the causes of maxillary growth restriction in
      cleft lip and palate patients. The aim of this study was to evaluate a simplified
      method to identify the causes of this growth impairment. We analyzed a sample of
      82 consecutively treated 5-year-old patients with unilateral complete cleft lip
      and palate, operated on by the same surgeon (R.B.). Multiple cephalometric
      measurements of the sample revealed a wide distribution of maxillary growth
      values. We selected Sella-Nasion A point angle (SNA) as a value describing
      maxillary position, and we arbitrarily isolated 2 "extreme" groups of patients:
      the 20 patients with the highest SNA were called "good growers" (group A), and
      the 20 patients with the lowest SNA were called "poor growers" (group B).
      Parameters investigated to search for different influencing factors within the
      groups were initial cast measurements, timing of lip and of
      gingivoalveoloplasty/palatal surgery, presence of lateral incisors, and family
      history of maxillary hypoplasia. Statistical differences were investigated with
      an independent-samples t-test. The 2 extreme groups had a significant difference
      (P < 0.01) in SNA and in lip protrusion relative to true vertical line. Cranial
      base angle was larger in group A. Timing of lip surgery in group B was earlier
      than in group A, but only close to significance. Timing of gingivoalveoloplasty
      did not differ. In group A, the permanent lateral incisor was missing in 20% of
      the patients; whereas in group B, it was missing in 82% of the patients (P <
      0.01). Selecting cleft lip and palate population with different growth pattern
      might help in isolating the factors responsible for maxillary growth impairment.
      Congenitally missing laterals that could indicate inherent tissue hypoplasia
      seems to be the most important factor.

PMID- 18812856
TI  - Some factors related to experimental snout growth.
AB  - This is a review and synthesis of several different studies over a 25-year period
      on growth of the rabbit snout. Included are growth of the nasal bone region,
      cellular activity of the cartilaginous nasal septum, growth at the frontonasal
      suture, growth of the snout after resection of the frontonasal suture, and growth
      of the snout after resection of the cartilaginous nasal septum in both young and
      adult rabbits. Each experiment contributed different knowledge to factors
      important in rabbit snout growth. The frontonasal suture is a site of rapid
      growth, as much as 1 cm in 4 weeks. However, after extirpation of the frontonasal
      suture, growth of the snout was not altered. Therefore, it was concluded that the
      frontonasal suture is a secondary and not a primary site of growth. After
      resection of the cartilaginous nasal septum in young rabbits, the snout became
      snubbed. This was not true in the adult rabbit, which maintained its usual length
      after resection of the nasal septum.

PMID- 18812857
TI  - BMP-2-based repair of large-scale calvarial defects in an experimental model:
      regenerative surgery in cranioplasty.
AB  - Pediatric craniofacial surgery is complicated by a shortage of autologous bone.
      Children between 2 and 10 years of age are especially problematic, as the dura
      has lost its potential to spontaneously heal large calvarial defects by
      approximately 2 years of age, and split calvarial grafts are often unavailable
      because of the underdeveloped diploic space until later childhood. We demonstrate
      the efficacy of a BMP-2-based system in repairing large-scale cranial defects in
      a rabbit model. Calvarial defects, 15 mm, were created in 18 adult New Zealand
      white rabbits, treated as follows: group 1, no repair (n = 6); group 2,
      absorbable collagen sponge (ACS) (n = 4); and group 3, recombinant human bone
      morphogenetic protein 2 delivered on ACS (rhBMP-2/ACS) (n = 8). Bone regeneration
      6 weeks postoperatively was evaluated by 2- and 3-dimensional standard computed
      tomography, micro-computed tomography. Analysis of variance was performed using
      SPSS. The generated bone was also evaluated histologically. After 6 weeks, group
      1 defects were on average 32.8% (SD, 8.8%) ossified. Group 2 defects were on
      average 34.4% (SD, 17.1%) ossified. Defects in group 3 were on average 96.9% (SD,
      3.7%) ossified, significantly (P < 0.005) more than the defects in groups 1 and
      2. rhBMP-2-induced bone was histologically and radiographically consistent with
      native bone. This study demonstrates the efficacy of rhBMP-2/ACS for the repair
      of calvarial defects in the rabbit model. rhBMP-2/ACS may offer a viable
      treatment option for craniofacial surgeons facing a shortage of bone, with the
      potential to replace autologous bone grafts and render their attendant
      morbidities obsolete.

PMID- 18812858
TI  - Open-tip approach: evolutions in rhinoplasty.
AB  - Modifications and innovations in open-structure rhinoplasty that have occurred as
      this technique has evolved are discussed. In addition, the philosophy and
      fundamentals of open-tip approach in rhinoplasty are reexamined. A retrospective
      review of representative patients in a hospital practice setting was performed.
      All surgical procedures were conducted in a department of plastic surgery of the
      University of Rome Tor Vergata. The preoperative and long-term results of each
      patient are compared to demonstrate the effectiveness of the described
      techniques. The fundamental philosophy of open-tip rhinoplasty is the maintenance
      of the integrity and strength of the nasal skeleton. Modifications of tip
      grafting techniques, along with additional domal grafting techniques, and a
      stronger focus on domal suturing techniques result in a softer contour and lack
      of tip tensions while maintaining structural support.

PMID- 18812859
TI  - Modification of the repair of a unilateral cleft lip.
AB  - The ideally repaired cleft lip should provide a symmetrical Cupid's bow,
      philtrum, and minimal scar. In the appearance of the upper lip, the philtrum
      plays a key role. The most popular method for unilateral cleft lip repair is the
      rotation advancement technique introduced by Millard. This technique requires the
      rotation of the non-cleft-side flap in a unilateral cleft lip. As the vertical
      discrepancy between the peaks of Cupid's bow is increased, the scarring becomes
      more evident. Also, where it crosses the philtral column in the oblique extension
      of the upper lip, it becomes apparent for the eye to notice. Thus, many surgeons
      have tried to modify this technique to improve the symmetry of the philtral
      columns. Therefore, I developed my technique, called the E (reversed) M (sided)
      skin extension (EMSEN) repair, including 2 perpendicular incisions in rotation
      flap and 2 equilateral flaps in advancement flap and muscle repositioning. We
      carried out the EMSEN technique to 20 consecutive (9 boys and 11 girls) patients
      with unilateral cleft. The mean age at repair was 10.1 years (range, 3 months to
      18 years). The postoperative outcomes were assessed with the subjective and
      objective scar assessment test. The mean follow-up time was 24.5 months. No early
      complication involving hematoma, infection, wound dehiscence, or partial or total
      flap loss was encountered. Three plastic surgeon committee members (randomized
      selected) reviewed the analysis of the color, texture, width, and thickness of
      the scar. It was found that most members of the plastic surgeon committee and
      patients or parents were very good and very happy, respectively. We eradicated
      some shortcomings in Millard's technique with this technique. E (reversed) M
      (sided) skin extension repair lengthens the vertical lip using the E-M flaps,
      resulting in a nonlinear incision such as W-plasty scar on the philtral ridge and
      forming symmetrical Cupid's bow, superior to Millard repair.

PMID- 18812860
TI  - Cleft lip and palate: technical strategies for the primary palatoplasty.
AB  - Surgical procedures in cleft lip and palate repair are continuously evolving. In
      the international literature, many guidelines exist dealing with different
      timings and surgical approaches. The authors present a technical strategy on
      primary palatoplasty and the guidelines for the surgical management of cleft lip
      and palate adopted by the Department of Maxillo-Facial Surgery of the Universita
      "La Sapienza" of Rome. This approach has been developed to allow a physiological
      facial growth and to preserve the essential main features of the stomatognathic
      system enclosing phonation and swallowing. Moreover, the authors present their
      own surgical technique for primary palate repair at 24 to 48 months with the
      galea-pericranium free flap.

PMID- 18812861
TI  - Surgical correction of Tessier number 0 cleft.
AB  - The no. 0-14 cleft involves the midline of the face and cranium. It may include
      both a true and a false median cleft lip, with or without associated hypotelorism
      or hypertelorism. The no. 0 cleft is the most common of the craniofacial clefts.
      The objective of this study was to review the functional outcome and aesthetic
      results of the different techniques applied for each case. We have conducted a
      retrospective analysis of our series consisting of 32 cases of Tessier no. 0
      cleft, in the period between 1997 and 2007. The patients were divided into 2
      groups: those with the true median cleft and those with the false median cleft.
      The clinical findings, lip malformation, alveolar cleft, nasal appearance, septal
      involvement, associated deformities, and surgical procedures, were all reviewed.
      Holoprosencephaly was present in 9 cases, with a false median cleft upper lip and
      an absence of the premaxilla, septum, and columella (only 1 patient underwent lip
      and columella reconstruction at 2 years of age). Nine patients had an incomplete
      median cleft lip. Seven of these cases had associated median alveolar cleft, and
      1 had an intranasal tumor, associated with lipoma of corpus callosum,
      characteristic of the Pai syndrome. Six cases of a bifid nose were seen, 2 of
      which were associated with an alveolar median cleft and hypertelorism. An
      isolated median alveolar cleft was present in 7 cases, 2 of them associated with
      a no. 30 cleft. This article presents a large series of Tessier no. 0 cleft,
      describing the differences between the false and the true median cleft. The
      surgical procedures may vary in relation to the type of involvement.

PMID- 18812862
TI  - Reconstruction of bilateral cleft lip and nose deformity.
AB  - Bilateral cleft lip and nose deformity can be divided into several types
      according to the extent of the cleft, protruding premaxilla, size of prolabium
      and nose deformity. Many repair techniques introduced in the literatures were not
      perfect because of the change of facial profile under the influence of facial
      growth.The author uses 1-stage cheiloplasty with nose correction for bilateral
      cleft lip and nose deformity. Early lip adhesion is used before definitive
      corrections in wide-cleft patients. The lateral mucosal flaps are used for the
      lining of alveolar cleft. The lateral orbicularis oris peripheralis flaps with
      the mucosa approximate in front of premaxilla with creation of a buccal alveolar
      sulcus and continuity of an orbicularis oris muscle. The lateral orbicularis
      marginalis muscle flaps with white skin roll and vermillion are used for
      reconstruction of the Cupid's bow. To enhance the median tubercle, prolabial
      vermilliomucosal flap is inserted into the gap between an approximated
      orbicularis peripheralis flap and an approximated orbicularis marginalis flap. Z
      plasty of the vestibular ridge and the fixation of lower lateral cartilages to
      dissect through alar rim excision achieve columella lengthening and tip
      projection. Lip scar revision is rare, but secondary nose correction using triple
      V-Y flap is frequent.

PMID- 18812863
TI  - A novel approach to cleft lip nose deformity: posterior dome graft technique.
AB  - The pathology of "nasal tip complex" remains as a problem to be solved in
      unilateral cleft lip nose deformity wherein open rhinoplasty and cartilage grafts
      are used frequently. For this reason, the research for the treatment of cleft
      side tip projection lost and ala depression still continues. Our technique is to
      put the cartilage graft at posterior dome area after the release of cleft-side
      ala from vestibular mucosa and skin to elevate the ala depression and tip
      projection. This technique has been used on 16 patients between the years 2003
      and 2007. This technique, different from the augmentation methods, aims to
      increase the direct lateral crura's elastic support strength and to support the
      new position of alar cartilage. This method will particularly be helpful in
      obtaining the long-term results in delayed and serious cases.

PMID- 18812864
TI  - Early secondary alveoloplasty in cleft lip and palate.
AB  - The aims of this study were to present a personal surgical technique throughout
      the review of international literature concerning surgical techniques,
      objectives, and outcomes in early secondary alveoloplasty and to describe our
      personal surgical techniques in alveolar bone defect repair in cleft lip and
      palate.Throughout a literature analysis, it is now settled that early secondary
      alveoloplasty could reestablish the continuity of alveolar bone and prevent upper
      dental arch collapse after presurgical orthopedic upper maxilla expansion; it
      also might give a good bone support for teeth facing the cleft and allow the
      eruption of permanent elements with the bone graft and rebalance the symmetry of
      dental arch, improve facial aesthetic, guarantee an adequate amount of bone
      tissue for a further prosthetic reconstruction with implant, and finally close
      the eventual oronasal fistula.The surgical technique we are presenting permitted
      a total number of 35 early secondary alveoloplasty on which a long-term follow-up
      is still taking place.We can assess that early secondary alveoloplasty must be
      performed before permanent canine eruption. Iliac crest is the suggested donor
      site for bone grafting; orthopedic and orthodontic treatments must be performed
      in association with surgery, and if there is the dental element agenesia, an
      implantation treatment must be considered.

PMID- 18812865
TI  - Secondary correction of deformities of the vermilion with exposed oral mucosa
      after cleft lip repair.
AB  - There is much discussion on the deformities of the vermilion after cleft lip
      repair such as a notch and uneven thickness of the vermilion because of
      insufficient union of the orbicularis oris muscle, vertical scar contracture of
      the vermilion, and suture sufficiency. However, it is relatively rare for a
      corrective method of the coloration and texture of the vermilion to become an
      issue. Prominent deformities can remain because of the exposed oral mucosa in the
      vermilion region. This exposure is due to the difference in the widths of the dry
      lip and wet lip. Furthermore, because wet lip is placed in a dry environment,
      there are a number of complaints such as constant scab formation. For such
      postoperative deformities of the vermilion, conventional secondary corrections
      have been performed such as Z-plasty and V-Y plasty. In our study, we used the
      scar of the vermilion as a pedicle flap and obtained relatively good results. The
      advantages of this method include not wasting tissue, relatively easy correction
      of coloration and texture of the vermilion, and formation of the labial tubercle.
      This method is thought to be a useful technique for vermilion deformities after
      cleft lip repair with exposed oral mucosa.

PMID- 18812866
TI  - A new modified forked flap with subcutaneous pedicles for adult cases of
      bilateral cleft lip nasal deformity: from normalization to aesthetic improvement.
AB  - In adult cases of bilateral cleft lip nasal deformity, an esthetically satisfying
      result can not be obtained only by manipulation inside the nose with the nasal
      tip pointing upward. The nasal tip should be made in a more anterior direction
      for nasal esthetic improvement. Additional tissue beyond the nose is needed, and
      the forked flap is a useful method in such cases. However, the blood circulation
      of long and narrow flaps containing the scar, especially after open rhinoplasty,
      is unstable. We have developed a new long and narrow forked flap that has a more
      stable blood circulation. The forked flap was made using two subcutaneous
      pedicles attached to the periphery of the each flap. We applied this flap to five
      adult cases of bilateral cleft lip nasal deformity. Four of the cases had the
      scar associated with the flying bird incision, and one case required no treatment
      after the primary repair. All the flaps took without signs of partial necrosis.
      In all cases, the nasal tip was projected forward with adequate columella
      elongation, and the profile was esthetically improved. In the final stage of
      correction for adult cases of bilateral cleft lip nasal deformity, this method,
      making maximum use of the tissue containing the scar in not only the white lip
      but also the vermilion, is very effective. It is very important to obtain nasal
      esthetic improvement for the adult patient with bilateral cleft lip nasal
      deformity.

PMID- 18812867
TI  - Isolated sphenoid sinus mucocele: etiology and management.
AB  - Sphenoid isolated lesions are rare; they occur in 2% to 3% out of all paranasal
      sinus lesions. Diagnosis is based on the endoscopic examination and computed
      tomography scan or magnetic resonance imaging of the maxillofacial area. In this
      study, we present patients with sphenoid mucocele in the Maxillo-facial Surgery
      Department, University of Rome La Sapienza, treated with the endoscopic
      technique. Moreover, a literature review is performed, dealing with the evolution
      of approaches to the sphenoid sinus. From January 2001 to January 2007, we
      treated 75 patients affected by paranasal sinus mucocele. Out of this number, 8
      patients (11%) presented an isolated localization in the sphenoid sinus. These
      patients were divided as follows: 5 involved the right sphenoid sinus and 3
      involved the left sphenoid sinus. Isolated sphenoid sinus disease is a rare
      entity that can result in serious sequelae if diagnosis and treatment are
      inappropriately delayed. In our study, we highlighted how the endoscopic approach
      allows the removal of even large mucocele with the use of 45-degree angle optic
      and if it is possible to control and remove lateral walls of the sphenoid sinus.
      In our experience, we shifted from a traditional approach to the endoscopic
      approach. At the present time, the endoscopic approach represents the gold
      standard for sphenoid sinus mucocele treatment because it allows the best view of
      the sphenoid sinus and grants a better restoring of respiratory function and a
      higher compliance from the patient.

PMID- 18812868
TI  - A simple method of fabricating nasal packing armed with ventilation tube.
AB  - Various packing materials have been used for closed reduction of nasal bone
      fractures or for septorhinoplasty. Most patients experience significant
      discomfort after the surgery owing to the lack of nasal breathing, and there are
      many reports concerning the complications related to nasal packing. Although
      nasal packing material with nasal airway maintenance is commercially available,
      the authors have developed an easy method to fabricate nasal packing materials
      with airway maintenance by using Merocel (Medtronic Xomed, Minneapolis,
      Minnesota) and a silastic suction catheter (16F, Qingdao Sewon Medical Co Ltd,
      Qingdae, China). The authors believe this idea, and innovation will be very
      useful for surgeons and patients of young age.

PMID- 18812869
TI  - Tip upturning and maxillary advancement: the UT angle.
AB  - Improving facial aesthetics has been shown to be a strong motivational factor in
      patients who decide to undergo orthognathic surgery. The nose is a keystone of
      facial aesthetics and is thus of central importance in planning and executing
      orthognathic surgery. Authors present their way to forecast the tip projection in
      anterior advancement of the maxilla. In the sample, only patients who, after Le
      Fort I, needed an advancement of the maxilla (56 patients) were considered. For
      each patient, the upturning angle was measured before and 6 months after surgery.
      In all the cases, a good aesthetic and functional result was reached; there were
      no big complications. From this study, it is possible to note that the upturning
      angle decreased by 0.6 to 0.8 degree each millimeter of maxillary advancement.

PMID- 18812870
TI  - Anthropometry of the external ear in children with cleft lip and palate in
      comparison to age-matched controls.
AB  - Comprehensive anthropometric measures in children with cleft lip (CL) and cleft
      palate (CP) have suggested that similar qualitative growth disturbances may be
      present in the auricle. We propose a study to evaluate and better understand
      auricular development in nonsyndromic children born with CL/CP. Our institution
      is a tertiary referral center for children with craniofacial anomalies. During a
      4-year period, we randomly selected 50 nonsyndromic children, aged 5 to 18 years,
      with CL or CP. Fifty age-matched control children without craniofacial anomalies
      were selected as a control group. Anthropometric measurement analysis was
      conducted to compare auricular length (sa-sba), width (pra-pa), attachment to the
      cranium (obs-obi), and degree protrusion. Auricular index was also calculated for
      each group. Using a multivariate analysis of variance, statistical analysis with
      a P < 0.001 demonstrates group differences when comparing ear length and ear
      protrusion in nonsyndromic children with CL/CP to age-matched controls. Ear
      length was greater in the control group, whereas ear protrusion (distance from
      the mastoid process to helical rim) was found to be decreased in the experimental
      group. Age and sex did not demonstrate significant differences in ear protrusion
      or length between the control and experimental groups. In nonsyndromic children
      with CL/CP, greater sensitivity should be given to the timing of auricular
      surgery. Comparisons of age-matched auricular measurements suggest that ear
      development may be altered in children with CL or CP. Further research is needed
      to investigate anthropological differences between nonsyndromic children with
      cleft and the normal population.

PMID- 18812871
TI  - Craniofacial morphology in children with operated complete unilateral cleft lip
      and palate.
AB  - The objective of the study was to compare the craniofacial characteristics of
      children with operated unilateral complete cleft lip and palate (UCLP) with those
      of noncleft children. Lateral and posteroanterior cephalometric radiographs of
      subjects with UCLP and controls who were matched for sex, age, and ethnic origin
      were analyzed and compared. There were a total of 21 subjects with UCLP (10 boys
      and 11 girls) from the Orthodontic Department of Selcuk University and 15
      controls (7 boys and 8 girls) from the Orthodontic Department of Ankara
      University. The nasal bone length in the group with cleft did not differ
      significantly from that in the control group. Subjects with UCLP included in the
      study appeared to have shorter faces, smaller mandibulae, greater lateral orbital
      width, and smaller sella turcicae compared with controls. Unilateral cleft lip
      and palate affects the intracranial morphology as well as dentofacial structures.

PMID- 18812872
TI  - Nasal shapes and related differences in nostril forms: a morphometric analysis in
      young adults.
AB  - Being aware of the morphologic differences in the nasal anatomy between men and
      women during the cosmetic rhinoplasty is essential because feminization of a male
      nose is not a very rare complication. Although there is no difference in the
      techniques of male and female rhinoplasty, the anthropometric differences have to
      be considered. This morphometric study evaluated the nasal shapes in both sexes
      and the related differences in the nostril forms. The nostril forms were
      separated into 4 main groups such as teardrop, heart shaped, round, and
      triangular. In this landmark-based morphometric study, significant relations of
      nostril forms to the nasal shape, frontonasal, and nasolabial angles were found.
      The results of this study should make us think about these relations of nostril
      forms to the nasal shapes and should be a basement for further clinical studies
      enhancing the plans of the corrective surgery.

PMID- 18812873
TI  - An isolated bilateral pure macrostomia in a 2-year-old girl.
AB  - Congenital macrostomia is a lateral orofacial cleft between the maxillary and
      mandibular components of the first branchial arch. Bilateral macrostomia is a
      rare entity. To date, 17 cases have been reported in the literature, with more
      than 50% isolated. We present a case of bilateral transverse facial cleft
      (macrostomia) in a 2-year-old girl. It was not associated with any other anomaly.
      The cleft involved only the soft tissues of the face. Hence, it was a pure
      macrostomia. She was the third female child of the family, with 2 elder sisters
      normal. Nutritional deficiency during intrauterine life and/or advanced maternal
      age can be causative factors. Transverse facial cleft was closed by Z-plasty
      incision, with good functional and aesthetic result.

PMID- 18812874
TI  - Rotation and advancement flap of the cheek in the treatment of rare craniofacial
      clefts.
AB  - The treatment of Tessier no. 3 and no. 4 clefts is controversial, and little is
      published because of their rarity. Frequently, many surgeries are necessary for
      correction of these defects, and in some cases, the outcomes are less than the
      ideal. Aware of that problem, we developed a procedure based on the Van der
      Meulen rotation and advancement flap of the cheek that may correct the cleft with
      1 simple procedure and also respects the aesthetic units of the face. We report 3
      patients presenting cleft no. 3 and 1 patient presenting cleft no. 4 and describe
      the rotation and advancement flap of the cheek technique used in their treatment.

PMID- 18812875
TI  - Maxillary advancement and transpalatal expansion using internal distraction in a
      patient with cleft lip and palate.
AB  - Correction of sagittal and transverse maxillary discrepancies in patients with
      cleft lip or palate remains a challenge for craniofacial surgeons. Distraction
      osteogenesis has revolutionized the conceptualization and approach to the
      craniofacial malformations and has become a reliable and irreplaceable part of
      the surgical armamentarium. We are reporting a case of sequential maxillary
      advancement and transpalatal expansion using internal distraction in a patient
      with unilateral cleft lip and palate presenting with severe maxillary sagittal
      and transverse deficiencies.

PMID- 18812876
TI  - Delayed development of mucocele in the fractured frontal sinus.
AB  - We present a case of delayed mucocele in the frontal sinus which occurred in 8
      years after the initial trauma.A 56-year-old man visited the hospital with a
      complaint of his left eye protruding for years. Eight years prior, he fell down
      stairs and sustained an injury on the head and was diagnosed to have a fracture
      of the anterior wall of frontal sinus. Frontal sinus mucosa was extirpated, and
      the space was obliterated with bovine artificial bone.Magnetic resonance imaging
      and computed tomography scans demonstrated an enlargement of the left orbit,
      measuring 4.0 cm x 2.6 cm, occupied by a huge mucocele. Through a bicoronal
      approach, a rectangular window (2 x 3 cm) was made on the anterior wall of
      frontal sinus. The grafted bovine bone was taken out to reach the mucocele, which
      distended down to the orbit. The mucocele was open, and yellowish, thick, pus
      like content was drained out with suction. Mucosa of the mucocele was removed as
      much as possible. The periorbita held in absence of most part of the orbital
      roof. Craniotomy site was undone after a free drainage of mucocele into the nasal
      cavity was ensured.The exhaustive ablation of all mucosa is a surgical principle
      to rid ultimate mucocele and depends on competent surgeons performing the
      procedure thoroughly.

PMID- 18812877
TI  - Nasal hair matrix cyst mimicking dermoid cyst.
AB  - Dermoid cysts are primarily observed in the head and neck region. Nasal dermoids
      are uncommon. The terms nasal dermoid, nasal epidermoid, and nasal sebaceous
      cysts are used interchangeably by clinicians. Hair matrix cyst is a variant of
      epidermal cyst resembling the pattern of pilomatrixoma. Formerly, nasal hair
      matrix cyst has not been reported at all. Here, an additional pathologic proof is
      presented as well.

PMID- 18812878
TI  - Reducing blood loss in synostosis surgery: the Liverpool experience.
AB  - Correction of craniosynostosis represents much of the workload in the pediatric
      designated UK craniofacial units. We reviewed recent operations as part of an
      ongoing unit audit cycle with outcome determined as blood use and complications
      or readmissions within 6 weeks of surgery. A pro forma was designed, and
      information from a chart search was collated on a Microsoft Excel (Microsoft,
      Seattle, WA) spreadsheet. Thirty-four patients were treated between March 2005
      and December 2006, including 13 who underwent scaphocephaly correction (SC) and
      21 who underwent fronto-orbital advancement and remodeling (FOAR). In the FOAR
      group, 13 patients received continuous autologous transfusion, and 8 patients did
      not. Continuous autologous transfusion system was not used in any of the patients
      who underwent SC. The results showed that allogeneic transfusion rates were 46 +/
      36% red cell volume (RCV) in FOAR when a cell saver was used and 50 +/- 21% RCV
      when it was not. There was no significant difference between each group; however,
      25% of patients received no transfusion in the cell saver group, whereas all
      patients undergoing FOAR were transfused in the non-cell saver group. Transfusion
      in SC was calculated as 26 +/- 25% RCV, and 33% of patients underwent SC without
      transfusion. In conclusion, we show that significant reductions in blood
      transfusion are possible in correction of craniosynostosis both with and without
      the use of cell savers by application of a simple protocol. Our findings support
      the recommendation that all of these cases be carried out in multidisciplinary
      units where high patient throughput allows both maintenance of skills and
      completion of audit cycles.

PMID- 18812882
TI  - A rare but disturbing complication of rhinoplasty: rhinorrhea.

PMID- 18812884
TI  - Dosing of remifentanil to prevent movement during craniotomy in the absence of
      neuromuscular blockade.
AB  - BACKGROUND: In neuroanesthesia practice, muscle relaxants may at times need to be
      avoided to facilitate intraoperative motor pathway monitoring. Our study's
      objective was to determine the optimal dose of remifentanil required to prevent
      movement after neurosurgical stimulation. METHODS: After Institutional Review
      Board approval and written informed consent, 132 patients undergoing elective
      craniotomy randomly received one of 12 remifentanil dose regimens (0.10 to 0.21
      microg/kg/min). Remifentanil was started before induction with propofol and
      succinylcholine. Anesthesia was maintained with isoflurane (0.6% end-tidal) in
      air/oxygen. During the study, movement was assessed on predetermined criteria by
      the anesthesiology, nursing, and neurosurgical teams. Heart rate and blood
      pressure were recorded every 5 minutes. We assessed the relationship between
      movement, hypotension, bradycardia, and dose using probit analysis and logistic
      regression. RESULTS: Sixty-five percent of the patients moved in response to
      surgical stimuli [95% confidence interval (CI): 49%-79%] at a remifentanil
      infusion rate of 0.10 microg/kg/min, and movement decreased to 21% (95% CI: 11
      35) at 0.21 microg/kg/min. The probability of movement was 50% at an infusion
      rate (95% CI) of 0.13 (0.10 to 0.15) microg/kg/min remifentanil and decreased to
      25% at an infusion rate of 0.19 (0.17 to 0.29) microg/kg/min. The probability of
      hypotension and bradycardia was 50% at 0.13 (0.10 to 0.15) microg/kg/min and 0.17
      (0.15 to 0.21) microg/kg/min, respectively. CONCLUSIONS: Higher doses of
      remifentanil lessen the risk of movement in the absence of muscle relaxants with
      surgical stimulation for elective craniotomy. Hypotension and bradycardia were
      common at higher doses. Even at the maximum dose (0.21 mcg/kg/min) there was a
      20% chance of movement. Adjunctive therapy is needed to ablate movement reliably,
      and to counteract the hypotensive effect of remifentanil. These findings may be
      helpful for clinicians administering remifentanil and isoflurane during
      procedures, where muscle relaxants may not be desirable.

PMID- 18812885
TI  - Xenon up-regulates several genes that are not up-regulated by nitrous oxide.
AB  - Xenon and other inhalational agents induce cell and organ effects through
      different and only partially elucidated molecular mechanisms. In this study, we
      explored the gene transcription consequences of xenon exposure compared with
      nitrogen or nitrous oxide exposure in rat brain. Seven-day-old Sprague Dawley
      rats (n=24, 8 for each group) were exposed for 120 minutes to 75% xenon and 25%
      oxygen, 75% nitrogen and 25% oxygen (air), or 75% nitrous oxide and 25% oxygen.
      Using suppression subtractive hybridization, relative real-time polymerase chain
      reaction, and northern blot analyses of on/off gene expression, we were able to
      identify a set of genes that are significantly up-regulated by xenon exposure.
      These genes may help explain some of the molecular mechanisms that account for
      the neuropreconditioning effects exerted by xenon relative to nitrous oxide and
      air.

PMID- 18812886
TI  - GABAergic mechanism of propofol toxicity in immature neurons.
AB  - Certain anesthetics exhibit neurotoxicity in the brains of immature but not
      mature animals. Gamma-aminobutyric acid (GABA), the primary inhibitory
      neurotransmitter in the adult brain, is excitatory on immature neurons via its
      action at the GABAA receptor, due to a reversed transmembrane chloride gradient.
      GABAA receptor activation in immature neurons is sufficient to open L-type
      voltage-gated calcium channels. As propofol is a GABAA agonist, we hypothesized
      that it and more specific GABAA modulators would increase intracellular free
      calcium ([Ca2+]i), resulting in the death of neonatal rat hippocampal neurons.
      Neuronal [Ca2+]i was monitored using Fura2-AM fluorescence imaging. Cell death
      was assessed by double staining with propidium iodide and Hoechst 33258 at 1 hour
      (acute) and 48 hours (delayed) after 5 hours exposure of neurons to propofol or
      the GABAA receptor agonist, muscimol, in the presence and absence of the GABA
      receptor antagonist, bicuculline, or the L-type Ca2+ channel blocker, nifedipine.
      Fluorescent measurements of caspase-3,-7 activities were performed at 1 hour
      after exposure. Both muscimol and propofol induced a rapid increase in [Ca2+]i in
      days in vitro (DIV) 4, but not in DIV 8 neurons, that was inhibited by nifedipine
      and bicuculline. Caspase-3,-7 activities and cell death increased significantly
      in DIV 4 but not DIV 8 hippocampal neuronal cultures 1 hour after 5 hours
      exposure to propofol, but not muscimol, and were inhibited by the presence of
      bicuculline or nifedipine. We conclude that an increase in [Ca2+]i, due to
      activation of GABAA receptors and opening of L-type calcium channels, is
      necessary for propofol-induced death of immature rat hippocampal neurons but that
      additional mechanisms not elicited by GABAA activation alone also contribute to
      cell death.

PMID- 18812887
TI  - N-methyl-D-aspartate (NMDA) antagonists--S(+)-ketamine, dextrorphan, and
      dextromethorphan--act as calcium antagonists on bovine cerebral arteries.
AB  - Ketamine, an intravenous anesthetic and a major drug of abuse, is a
      noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist. Ketamine's
      enantiomer, S(+)-ketamine, acts stereoselectively on neuronal NMDA receptors. The
      purpose of this in vitro study was to compare the direct effects of S(+)
      ketamine, 2 other noncompetitive NMDA receptor antagonists (dextrorphan and
      dextromethorphan), and the calcium entry blocker nimodipine on the cerebral
      vasculature, using bovine middle cerebral arteries as an experimental model.
      Arterial rings were mounted in isolated tissue chambers equipped with isometric
      tension transducers to obtain pharmacologic dose-response curves. In the absence
      of exogenous vasoconstrictors, the NMDA antagonists or nimodipine had negligible
      effects on cerebral arterial tone. When rings were preconstricted with either
      potassium or the stable thromboxane A2 mimetic U46619, the NMDA antagonists and
      nimodipine each produced dose-dependent relaxation. Prior endothelial stripping
      had no effect on subsequent drug-induced relaxation of K+-constricted rings. In
      Ca2+-deficient media containing either potassium or U46619, the NMDA antagonists
      and nimodipine each produced competitive inhibition of subsequent Cainduced
      constriction. In additional experiments, arterial strips were mounted in isolated
      tissue chambers to directly measure calcium uptake, using 45calcium (45Ca) as a
      radioactive tracer. The NMDA antagonists and nimodipine each blocked potassium
      stimulated or U46619-stimulated Ca2+ uptake into arterial strips. These results
      indicate that S(+)-ketamine, dextrorphan, and dextromethorphan, like nimodipine,
      directly dilate cerebral arteries by acting as calcium antagonists; they all
      inhibit 45Ca uptake through both potential-operated (potassium) and receptor
      operated (U46619) channels in cerebrovascular smooth muscle.

PMID- 18812888
TI  - Evaluation of a bedside monitor of regional CBF as a measure of CO2 reactivity in
      neurosurgical intensive care patients.
AB  - OBJECTIVE: Mild hyperventilation remains a key element in the management of
      elevated intracranial pressure. However, a harmful effect of hyperventilation on
      the development or deterioration of ischemic lesions has been shown in patients
      after severe head trauma. The objective of this study was to investigate the
      clinical feasibility and reliability of continuous monitoring of regional
      cerebral blood flow (rCBF) during mild hyperventilation using a thermodiffusion
      probe. CO2 reactivity was calculated. The measurement of the partial pressure of
      oxygen (PtiO2) in the cerebral tissue served as a reference parameter. METHODS:
      An intraparenchymal intracranial pressure sensor, a multiparameter probe for
      determining the partial pressure of cerebral gases (pHti, PtiO2, PtiCO2), and a
      thermodiffusion probe for measuring rCBF were used in 10 intensive care patients.
      All patients were analgosedated and received pressure-controlled mechanical
      ventilation. Controlled mild hyperventilation was carried out on 2 consecutive
      days. CO2 reactivity was determined in relation to both CBF and PtiO2. RESULTS:
      Controlled hyperventilation resulted in a rCBF reduction from 30+/-3 mL/100 g/min
      to 25+/-2.4 mL/100 g/min (-17%; P<0.05) on the first day of examination and 31+/
      3.6 mL/100 g/min to 22+/-4.9 mL/100 g/min (-29%; P<0.05) on the second day.
      Likewise, mild hyperventilation resulted in a reduction of regional cerebral
      tissue oxygen partial pressure from 20+/-2.9 mm Hg to 15+/-4 (-25%; P<0.05) on
      the first day and 20+/-3.1 mm Hg to 14+/-1.5 mm Hg (-30%; P<0.05) on the second.
      CONCLUSIONS: Continuous monitoring of regional CBF, using an intraparenchymally
      placed thermodiffusion probe, seems to be a simple and safe bedside technique.
      The promise of reliably monitoring and interpreting additional parameters such as
      PtiO2 and PtiCO2 warrants further investigation.

PMID- 18812889
TI  - Patient-controlled epidural analgesia (PCEA) for postoperative pain control after
      lumbar spine surgery.
AB  - Spine surgery remains one of the most common procedures for patients with a wide
      variety of spine disorders. Postoperative pain after major spine surgery is
      moderate to severe. We retrospectively reviewed 245 medical records of adult
      patients undergoing major spine surgery who received either patient-controlled
      epidural analgesia based on local anesthetics and opioids or patient-controlled
      intravenous analgesia as postoperative pain management. Several outcomes were
      analyzed including pain intensity, opioid consumption, time to endotracheal
      extubation, the incidence of deep venous thrombosis, and length of stay in the
      hospital. We found that the use of patient-controlled epidural analgesia provided
      better postoperative analgesia [median (quartiles) verbal analog scale score of 4
      (3, 5) vs. 5 (3, 6)] and decreased the amount of opioid consumption
      postoperatively [median of 0 mg (0, 3) vs. 35 mg (0, 150)] compared with patient
      controlled intravenous analgesia. Also, a substantially higher number of patients
      in the patient-controlled intravenous group required opioids as rescue analgesia.
      Incidences of deep venous thrombosis, operating room extubation, and length of
      stay in the hospital were not associated with the analgesic technique. The
      results of this study suggest that the use of neuroaxial analgesia for the
      management of postoperative pain associated with major spine surgery may have
      some beneficial properties over intravenous analgesia. The use of a reduced
      amount of opioids by patients with epidural analgesia may be relevant because of
      potential fewer side effects mainly in elderly patients. Several limitations
      related to the retrospective nature of the study are described. Prospective
      randomized-controlled trials are needed to understand and elucidate the optimum
      regimen of postoperative pain management after major spine surgery.

PMID- 18812892
TI  - Cardiovascular responses during percutaneous radiofrequency thermocoagulation
      therapy in primary trigeminal neuralgia: an explanation of the trigeminocardiac
      reflex?

PMID- 18812893
TI  - Evidence-based analysis of removal of orthopaedic implants in the pediatric
      population.
AB  - BACKGROUND: Requested project of the Pediatric Orthopaedic Society of North
      America Evidenced-Based Medicine Committee. METHODS: The English literature was
      systematically reviewed for scientific evidence supporting or disputing the
      common practice of elective removal of implants in children. RESULTS: Several
      case series reported implant removal, but none contained a control group with
      retained implants. No articles reported long-term outcomes of retained implants
      in large numbers. Several small series describe complications associated with
      retained implants without evidence of causation. The existing literature was not
      amenable to a meta-analysis. By compiling data from the literature, it is
      possible to calculate a complication rate of 10% for implant removal surgery. The
      complication rate for removal of implants placed for slipped capital femoral
      epiphysis is 34%. Articles regarding postmarket implant surveillance and basic
      science were also reviewed. CONCLUSIONS: There is no evidence in the current
      literature to support or refute the practice of routine implant removal in
      children.

PMID- 18812894
TI  - Early outcomes after hip arthroscopy for femoroacetabular impingement in the
      athletic adolescent patient: a preliminary report.
AB  - BACKGROUND: Hip arthroscopy is becoming a more popular method of treatment of
      pediatric hip disorders. We report on the treatment of femoroacetabular
      impingement (FAI) in the adolescent population. METHODS: Between March 2005 and
      May 2006, 16 patients (aged 16 years or younger) underwent hip arthroscopy for
      FAI. There were 14 female adolescents and 2 male adolescents, with 1 patient
      undergoing a bilateral procedure. Five patients had isolated pincer impingement,
      2 had isolated cam impingement, and 9 had mixed pathology. All patients had
      labral pathology. Seven patients were treated with suture anchor repair of the
      labrum and 9 with partial labral debridement. Subjective data were collected from
      each patient during their initial visit and at follow-up after surgery.
      Subjective data included the modified Harris hip score (MHHS), patient
      satisfaction, and hip outcome score (HOS) activities of daily living (ADL), and
      sports subscales. RESULTS: The mean age at the time of arthroscopy was 15 years
      old (range, 11-16 years). The mean preoperative MHHS was 55 (range, 33-70), HOS
      ADL was 58 (range, 38-75), and HOS sport was 33 (range, 0-78). The mean time from
      injury to surgery was 10.6 months (range, 6 weeks-30 months). The mean time to
      follow-up was 1.36 years (range, 1-2 years). The mean postoperative MHHS improved
      35 points to 90 (range, 70-100; P = 0.005), postoperative HOS ADL improved 36
      points to 94 (range, 74-100; P = 0.001), and postoperative HOS sport score
      improved 56 points to 89 (range, 58-100; P = 0.001). The mean patient
      satisfaction score was 9 (range, 9-10). CONCLUSIONS: Hip arthroscopy for FAI in
      the adolescent population produces excellent improvement in function and a high
      level of patient satisfaction in the short-term.

PMID- 18812895
TI  - To what extent does remodeling of the proximal femur and the acetabulum occur
      between disease healing and skeletal maturity in Perthes disease? A radiological
      study.
AB  - Radiographs of 75 children with unilateral disease were studied to quantify the
      extent of remodeling of the proximal femur and the acetabulum between healing and
      skeletal maturity in children with Perthes disease. The mean ages at disease
      onset, healing, and skeletal maturity were 8.3, 11.9, and 15.5 years,
      respectively. Fifty-seven children were treated surgically by subtrochanteric
      varus osteotomy with trochanteric epiphyseodesis; the remaining 18 children were
      treated nonoperatively. Assessment of the Mose's index and Stulberg grading and
      measurements of the proximal femur and the acetabulum were made at healing and at
      skeletal maturity. The Stulberg grade and the Mose's index did not change between
      healing and skeletal maturity in 88% and 95% of children, respectively. In
      operated children, there was significant improvement of the articulotrochanteric
      distance, acetabular depth, neck-shaft angle, and Sharp's angle between disease
      healing and skeletal maturity, but no such changes occurred in children who were
      not operated on. We conclude that because little change occurs in the shape of
      the femoral head and congruity of the hip between healing and skeletal maturity,
      the outcome of treatment based on these 2 variables can be assessed once the
      disease heals in children with late-onset Perthes disease.

PMID- 18812896
TI  - Out-toeing and in-toeing in patients with Perthes disease: role of the femoral
      hump.
AB  - BACKGROUND: Some patients with Perthes disease develop abnormal gait in the
      transverse plane, that is, out-toeing or in-toeing. Considering that this
      phenomenon occurs mainly in patients who presented late without previous
      treatment or failed in the containment treatment, we postulated that the deformed
      femoral head and its impingement to the acetabulum may play an important role in
      the pathomechanism of this abnormal gait. METHODS: Three-dimensional computed
      tomography (CT) and gait analysis were performed for 9 patients with late
      presenting unilateral Perthes disease, who recently developed out-toeing (n = 5)
      or in-toeing (n = 4) gaits without torsional problems or foot deformities.
      Deformity of the femoral head was investigated, with special attention to the
      location and size of the femoral "hump." Kinematic gait data were used to analyze
      the difference in the impinging pattern of the hip joint between the 2 opposite
      groups of patients. The gait parameters evaluated were foot progression angle,
      hip rotation, and pelvis rotation in the transverse plane; hip flexion and
      extension in the sagittal plane; hip adduction and abduction in the coronal
      plane. RESULTS: In the 5 out-toeing patients, all affected hips had anteriorly
      deviated femoral hump, and they were externally rotated in the CT gantry with the
      hump facing the anterolateral part of the hip joint. On the other hand, all
      affected hips of the 4 in-toeing patients had laterally deviated hump, and they
      were internally rotated in the CT gantry with the hump facing the anterolateral
      part of the hip joint. Gait analysis showed abnormal hip rotation and
      compensatory pelvis rotation. Maximal flexion was decreased in all out-toeing
      hips. Unintentional adduction was observed in all in-toeing hips. CONCLUSIONS:
      The results suggest that out-toeing and in-toeing gaits are apparently caused by
      the compensatory rotation of the proximal femur to avoid impingement by placing
      the femoral hump to the relatively deficient anterolateral part of the hip joint.

PMID- 18812897
TI  - Increased intracapsular pressures after unstable slipped capital femoral
      epiphysis.
AB  - BACKGROUND: Osteonecrosis of the femoral head is the most dreaded complication
      associated with an unstable slipped capital femoral epiphysis (SCFE). We
      hypothesize that the hip joint pressure will be increased in unstable slips,
      confirming that emergent treatment and decompression are warranted. METHODS:
      Thirteen unstable SCFE hips were evaluated. Hip pressure monitoring was
      performed. Postcapsulotomy measurements were also performed in all of the
      patients. Five of these under gentle manipulation. Six patients underwent
      measurement of the hip pressure on the unaffected side. RESULTS: The mean
      pressure on the affected hip was 48 mm Hg. The mean pressure on the unaffected
      side was 23 mm Hg. There was a significant increase in intraarticular hip
      pressure after attempted manipulation (mean, 75 mm Hg). DISCUSSION: Hip pressures
      are increased in unstable SCFE to levels higher for those of a compartment
      syndrome probably causing a tamponade effect. There is a need to perform a
      capsulotomy if manipulation is performed.

PMID- 18812898
TI  - Bilateral anterior hip dislocation in a child with Aarskog syndrome: a case
      report.
AB  - Both Aarskog syndrome and atraumatic anterior hip dislocation are rare entities.
      Aarskog syndrome is an X-linked recessive disorder with facial, digital, and
      genital anomalies and is associated with varying degrees of ligamentous laxity.
      This is believed to be the only known reported case of bilateral anterior
      voluntary dislocating hips in an ambulatory child and the only reported case of
      hip dislocation in a child with Aarskog syndrome. Staged bilateral varus
      derotational femoral osteotomies and Dega osteotomies were successfully
      performed. Hardware was removed 1 year after the second operation. The patient
      has been asymptomatic at 2 years' follow-up. This article calls attention to the
      features of Aarskog syndrome and potential orthopaedic concerns.

PMID- 18812899
TI  - How to determine the upper level of instrumentation in Lenke types 1 and 2
      adolescent idiopathic scoliosis: a prospective study of 132 patients.
AB  - BACKGROUND: The selection of fusion levels continues to be controversial in
      adolescent idiopathic scoliosis (AIS). The classifications of King and Lenke
      remain the most widely used, but recent studies have demonstrated their
      shortcomings, including poor interobserver reproducibility. We propose a method
      of preoperative planning that is independent of anatomical classifications, based
      on the anticipated effect of curve reduction. The objectives of this preoperative
      strategy are (1) to achieve satisfactory T1 tilt and shoulder balance and (2) to
      restore balance in the coronal and sagittal planes. The purpose of the present
      study was to evaluate the results of our strategy of deciding the proximal level
      of arthrodesis in Lenke types 1 and 2 AIS. METHODS: We included 132 adolescents
      operated on for thoracic AIS by posterior instrumentation. The choice of the
      proximal fusion level was based on preoperative analysis of the rigidity of the
      proximal curvature, T1 tilt, and shoulder balance. The preoperative,
      postoperative, and last follow-up radiographs were digitized then analyzed using
      computer software. Radiological parameters were compared using paired t tests.
      RESULTS: Average age at the time of surgery was 15.2 years (SD, 1.7 years). Mean
      follow-up was 30.2 months. The clavicle angle and T1 tilt were significantly
      improved in both Lenke types 1 and 2 curves. No correlation was found between T1
      tilt and shoulder balance. At last follow-up, 89% of the patients satisfied all
      criteria for balance. CONCLUSIONS: The results of the present preoperative
      strategy, to which we adhered in 97% of cases, are encouraging and show that the
      systematic instrumentation of the entire proximal curvature is not justified in
      Lenke type 2 curves. However, long-term consequences of the residual T1 tilt need
      to be studied further.

PMID- 18812900
TI  - Lower limb alignment in children: reference values based on a full-length
      standing radiograph.
AB  - BACKGROUND: A full-length standing anteroposterior radiograph of the entire lower
      extremity has become the standard imaging modality for assessing lower limb
      alignment. Although reference values of frontal plane deformity parameters based
      on adult subjects have been established, such values may not be applicable to the
      pediatric population. The purpose of our study was to establish the reference
      values of frontal plane alignment and joint orientation angles in children based
      on a standing full-length radiograph. METHODS: A database at a single institution
      was searched for patients who were aged between 1 and 18 years at the time of
      undergoing a standing full-length radiograph of the lower extremities.
      Radiographic analysis of lower extremities without any abnormalities was
      performed by a single observer. Mechanical axis deviation, lateral distal femoral
      angle (LDFA), medial proximal tibial angle (MPTA), tibiofemoral angle, joint line
      convergence angle, and mechanical axis station were calculated at yearly
      intervals. The data were summarized using descriptive statistics, and simple
      regression analysis was performed to determine the relationship between the
      patients' age and the magnitude of LDFA and MPTA. RESULTS: A total of 354
      unaffected lower extremities in 253 children were analyzed. Between the ages of 1
      and 2 years, the tendency for varus alignment of the lower limb was related to
      the varus orientation of the distal femur with a mean LDFA of 95 degrees (95%
      confidence interval [CI], 93-97 degrees). By the age of 3 years, the limb
      alignment changed to valgus related to a combination of decreasing varus
      orientation of the distal femur and a mild increase in valgus orientation of the
      proximal tibia with the mean MPTA changing from 89 degrees (95% CI, 88-90
      degrees) to 91 degrees (95% CI, 90-92 degrees). After the age of 7 years, all
      joint orientation angles were noted to be within the range of reference values
      that are available for the adult population. Despite changes in limb alignment
      with growth, the mean mechanical axis of the lower extremity remained within the
      central half of the knee joint in children older than 1 year of age. CONCLUSIONS:
      The change in alignment of the lower limb from 1 to 4 years of life from varus to
      valgus is primarily related to a progressive decrease in varus orientation of the
      distal femur. In children younger than 7 years old, age-specific reference values
      for joint orientation angles of the lower extremity should be used instead of
      values derived from adult subjects.

PMID- 18812901
TI  - Correction of lower limb deformities in children with renal osteodystrophy by the
      Ilizarov method.
AB  - BACKGROUND: Children with renal osteodystrophy (ROD) may develop severe angular
      deformities of the limbs. Various methods, both medical and surgical, have been
      described for correction of these deformities, but a literature search showed
      only 1 child previously treated by the Ilizarov method. The purpose of this study
      was to characterize the deformities found in our group of patients and to
      describe our experience in treating these patients with the Ilizarov method.
      METHODS: Correction of angular deformity by the Ilizarov method was performed on
      8 limb segments in 5 patients with ROD. Mean age was 14.9 years. Two patients
      were on hemodialysis, and 3 had functioning kidney grafts. Surgery was deferred
      until stabilization of metabolic parameters. RESULTS: There was 1 varus and 7
      valgus deformities. Preoperative coronal deformity averaged 29 degrees (18-38
      degrees). The Ilizarov apparatus was used in all cases. Correction time averaged
      23 days (20-28 days). The time from completion of correction to frame removal
      averaged 71 days (48-113 days). There were no changes in metabolic parameters or
      frequency of hemodialysis throughout the treatment. Restoration of a normal
      mechanical axis was achieved in 4 of the 5 patients. One case failed due to
      intraarticular instability. There were no major complications. Minor
      complications included pin tract infections, which responded to antibiotic
      treatment, and premature consolidation in 1 case. Follow-up averaged 6.5 years (1
      10 years). The alignment obtained at surgery was maintained in all 4 patients,
      and they are functional and symptom-free. The patient for whom the surgery failed
      remains wheelchair-bound. CONCLUSIONS: The Ilizarov method was found to be safe
      and effective for correction of malalignment due to ROD. Optimization of
      metabolic parameters is essential before surgery and throughout correction. The
      procedure is contraindicated in patients with significant intraarticular knee
      pathology.

PMID- 18812902
TI  - Progressive genu valgum resulting from idiopathic lateral distal femoral physeal
      growth suppression in adolescents.
AB  - BACKGROUND: Progressive genu varum with disturbance of medial tibial physeal
      growth (classic Blount disease) is a well-studied phenomenon, and in rare cases,
      genu varum can occur because of medial distal femoral physeal growth disturbance
      (so-called femoral Blount disease). To our knowledge, progressive genu valgum
      caused by disturbance of lateral distal femoral physeal growth has not been
      described. METHODS: This article presents the history, clinical findings, imaging
      studies, results of surgical treatment, and speculation regarding the etiology of
      this disorder in 2 girls. RESULTS: Both patients were overweight girls without a
      history of injury or prior medical disorder who presented with relatively rapid
      progression of knock-kneed deformity. Magnetic resonance imaging studies
      demonstrated unusual circular peglike disturbances of the lateral distal femoral
      physes. Treatments in both cases included corrective distal femoral osteotomy and
      epiphysiodesis to prevent further deformity. CONCLUSIONS: Obesity and repetitive
      microtrauma, superimposed on genetic factors (physis that is sensitive to
      compressive forces), may contribute to the etiology of this rare disorder.

PMID- 18812903
TI  - Progressive valgus deformity after curettage of benign lesions of the proximal
      tibia.
AB  - BACKGROUND: Progressive valgus deformity after proximal tibial metaphyseal
      fractures in pediatric patients has been well described, although the
      pathophysiology is not clear. We performed a retrospective study to evaluate the
      occurrence of progressive tibia valga after curettage of benign bone lesions of
      the tibia. METHODS: During a 6-year period, we performed curettage and bone
      grafting of benign bone lesions of the tibia in 20 patients aged 16 years and
      younger. Radiographs and clinical notes were reviewed. The diagnosis, age, sex,
      location of lesion, surgical approach, physeal arrest, limb-length discrepancy,
      deformity, and treatment were documented. RESULTS: Four patients subsequently
      developed progressive tibia valga (mean, 12 degrees; range, 7-21 degrees).
      Progressive valgus deformity occurred in 4 of 5 patients younger than 10 years
      old who had curettage of lesions of the proximal tibial metaphysis. Deformity did
      not occur in any of the 13 patients older than 10 years (range, 13-16 years) or
      in any of the 8 patients who had curettage of the distal tibia (age range, 6-14
      years). In patients who developed tibia valga, the deformity progressed during
      the first 6 to 17 months postoperatively and then stabilized. One patient
      required corrective osteotomy at age 12 years for a symptomatic 21-degree
      deformity 3 years after curettage. The other 3 patients with tibia valga remained
      asymptomatic and demonstrated partial correction of their deformities, currently
      ranging from 3 to 7 degrees with a mean follow-up of 31 months (range, 19-47
      months). CONCLUSIONS: Progressive tibia valga seem to be relatively common in
      patients younger than 10 years who have had curettage of the proximal tibial
      metaphysis. This potential sequela should be discussed thoroughly with the
      patient's parents before proceeding with surgery, and patients should be followed
      and evaluated for this postoperatively.

PMID- 18812904
TI  - Characteristic factors of ankle valgus with multiple cartilaginous exostoses.
AB  - BACKGROUND: Ankle valgus is one of the most common deformities in multiple
      cartilaginous exostoses (MCEs). However, the characteristic factors of ankle
      valgus are not well known. METHODS: To determine the characteristic factors of
      ankle valgus in MCE, we investigated 62 ankles in 33 patients (23 males, 10
      females) with no history of surgical treatment of ankles with MCE. Mean age at
      investigation was 11 years 4 months (range, 2 years 7 months-17 years 1 month).
      We evaluated Taniguchi classification, tibiotalar angle (ankle valgus), site of
      exostoses in the distal tibia and distal fibula, fibular shortening (Malhotra
      classification), and correlations between these factors. RESULTS: According to
      Taniguchi classification, patients were classified as group II (n = 8), group III
      (n = 18), or unknown (n = 7). Mean tibiotalar angle was 5.1 degrees (range, -4 to
      20 degrees) in males and -0.8 degrees (range, -5 to 7 degrees) in females.
      Significant differences in ankle valgus were found between sexes within the same
      age group, and ankle valgus progressed with age in males. Ankles with involvement
      of both lateral distal tibia and medial distal fibula showed significantly more
      severe ankle valgus than ankles with involvement of the lateral distal tibia
      alone or no involvement. In Malhotra classification, all except 1 ankle showed
      station 0 in females. All cases of station II or III involved males and degree of
      fibular shortening correlated with ankle valgus in males. Taniguchi group III was
      associated with more frequent involvement of both lateral distal tibia and medial
      distal fibula in males, and greater frequency of both fibular shortening and
      ankle valgus with >or=10 degrees was seen compared with Taniguchi group II.
      CONCLUSIONS: Several characteristic factors of ankle valgus in MCE seem to
      predict progression.

PMID- 18812905
TI  - Biomechanical analysis of supracondylar humerus fracture pinning for slightly
      malreduced fractures.
AB  - BACKGROUND: The most common position of malreduced type III supracondylar humerus
      (SCH) fractures is internal rotation and medial collapse of the distal fragment.
      The purpose of this study was to determine the effect of SCH fracture rotational
      deformity on stability with various pin configurations. Specifically, is the
      biomechanical stability lost when an SCH fracture is pinned in slight
      malreduction (compared with anatomical pinning) improved by adding a third pin?
      METHODS: Sixty-four synthetic humeri were sectioned in the mid-olecranon fossa to
      simulate an SCH fracture. Specimens were randomized to an anatomically reduced
      group or a group with 20 degrees of distal fragment internal rotation (n = 32 per
      group). Each was randomized to one of 4 pin configurations: 2 laterally divergent
      pins, 2 crossed pins, 3 laterally divergent pins, or 2 lateral with 1 medial pin
      (n = 8 per group). All fractures were stabilized with 1.6 mm (0.062 in) Kirschner
      wires. Models were tested in extension, varus, and valgus for 10 cycles between 5
      N and 50 N. Internal and external rotations were tested between +/-1 Nm. Data for
      fragment stiffness (newtons per millimeter or newton millimeters per degree) were
      analyzed with a 2-way analysis of variance (p < 0.05). RESULTS: Internally
      rotated fractures were significantly less stable than the anatomically reduced
      group for external rotation, internal rotation, and varus loading regardless of
      pin configuration. Within the malreduced group, 3-pin configurations were more
      stable than 2-pin configurations in internal rotation, varus, and extension
      loading. Two lateral divergent pins were similar to 2 crossed pins, except in
      extension, where 2 lateral pins had greater stiffness. CONCLUSIONS: Construct
      stiffness for malreduced specimens after pinning was less than those pinned with
      an anatomical reduction when loaded in varus, internal rotation, and external
      rotation. For simulated fractures with residual internal rotation, the addition
      of a third Kirschner wire compared with an anatomically reduced 2-crossed-pin
      configuration resulted in increased stiffness of the model for all loading
      directions. CLINICAL RELEVANCE: Consider a 3-pin pattern, either 3 laterally
      divergent pins or 2 lateral pins and 1 medial pin, for SCH fractures when a less
      than complete anatomical reduction is obtained.

PMID- 18812906
TI  - Nerve palsy after hamstring lengthening in patients with cerebral palsy.
AB  - BACKGROUND: The purpose of this study was to assess the incidence of, risk
      factors for, and treatment of nerve palsy after hamstring lengthening in children
      with cerebral palsy. METHODS: A medical record review of patients with cerebral
      palsy who had hamstring lengthening between 1994 and 2005 was performed. Data
      included the preoperative popliteal angle, the presence of a knee flexion
      contracture, postoperative pain management, and type of immobilization. The
      presence of postoperative nerve palsy was established based on the recording of
      numbness, loss of motor function in the foot, or hypersensitivity of the foot in
      the inpatient record or the postoperative clinic notes. The need for medical
      management and time to resolution of symptoms were noted. RESULTS: A total of 292
      children underwent 329 hamstring lengthening surgeries. The mean age at surgery
      was 9.5 years (range, 2.5-18 years). Twenty-eight patients (9.6%) experienced
      postoperative nerve palsy. Time to recognition of the palsy ranged from 4 hours
      to 72 days. Patients diagnosed within 24 hours had loss of motor function and/or
      lack of sensation of the toes. Patients diagnosed from 8 to 72 days
      postoperatively had dysesthesias of the feet. Treatment of early palsies
      consisted of the removal of immobilization, bivalving of casts, or wedging casts
      into flexion. Fourteen of 28 patients were treated with Neurontin. Twenty-two of
      25 patients with adequate follow-up recovered nerve function. Older children,
      noncommunicative patients, nonambulatory patients, and those who had epidural
      pain management were at statistically significant higher risk for postoperative
      palsy. The trend for palsies in spastic quadriplegic patients and after repeat
      lengthening procedures did not reach significance. There was no significant
      relationship between popliteal angle or the presence of a knee flexion
      contracture and development of nerve palsy. CONCLUSIONS: Nerve palsy occurred in
      9.6% of patients undergoing hamstring lengthening. Although the greatest risk was
      in noncommunicative adolescents who were nonambulatory, a small number of younger
      ambulatory patients developed palsies as well, so that all patients must be
      considered at risk. Vigilance in patients with epidural pain control to avoid
      excessive hip flexion and/or knee extension is warranted. Treatment is immediate
      knee flexion. Resolution of symptoms occurred in 82.1% of patients.

PMID- 18812907
TI  - The impact of the current epidemiology of pediatric musculoskeletal infection on
      evaluation and treatment guidelines.
AB  - BACKGROUND: Methicillin-resistant Staphylococcus aureus is thought to have led to
      an increase in the incidence of severe musculoskeletal infection in children. Our
      purpose was (1) to compare the current epidemiology of musculoskeletal infection
      with historical data at the same institution 20 years prior and (2) to evaluate
      the spectrum of the severity of this disease process within the current
      epidemiology. METHODS: Children with musculoskeletal infection, treated between
      January 2002 and December 2004, were studied retrospectively. Diagnoses of
      osteomyelitis, septic arthritis, pyomyositis, and abscess were established for
      each child based on overall clinical impression, laboratory indices, culture
      results, radiology studies, and intraoperative findings. Comparison was made with
      the experience reported at the same institution in 1982. Children within each
      diagnostic category were compared with respect to mean values of C-reactive
      protein and erythrocyte sedimentation rate at admission, number of surgical
      procedures, intensive care unit admissions, identification of deep venous
      thrombosis, and length of hospitalization. RESULTS: Five hundred fifty-four
      children were studied (osteomyelitis, n = 212; septic arthritis, n = 118;
      pyomyositis, n = 20; and deep abscess, n = 204). The annualized per capita
      incidence of osteomyelitis increased 2.8-fold, whereas that of septic arthritis
      was unchanged when compared with historical data from 20 years prior. Methicillin
      resistant Staphylococcus aureus was isolated as the causative organism in 30% of
      the children. We identified increasing severity of illness according to a
      hierarchy of tissue involvement (osteomyelitis > septic arthritis > pyomyositis >
      abscess) and according to the identification of contiguous infections within in
      each primary diagnostic category. CONCLUSIONS: The incidence of musculoskeletal
      infection appears to have increased within our community. We found that a more
      comprehensive diagnostic classification of this disease is useful in
      understanding the spectrum of the severity of illness and identifying those who
      require the greatest amount of resources. Magnetic resonance imaging is useful
      early in the diagnostic process to enable a more detailed disease classification
      and to expedite surgical decisions. The recognition of the incidence of
      methicillin-resistant Staphylococcus aureus within our community has also led to
      a change in empirical antibiotic selection.

PMID- 18812908
TI  - Proximal tibial epiphyseal intraosseous schwannoma: a rare entity.
AB  - Schwannoma is a benign nerve sheath tumor most commonly located in the soft
      tissue. Occasionally, schwannomas involve osseous structures. The rarity of
      osseous involvement leads to omission of schwannoma from the initial differential
      diagnosis in the majority of cases. Intraosseous schwannomas arising in children
      have not been reported. We present the case of a schwannoma affecting the
      proximal tibial epiphysis in a growing child. Intraosseous schwannomas should be
      included in the differential diagnosis of lytic epiphyseal benign-appearing bone
      lesions in children. Its radiographic characteristics mimic those of benign
      chondroblastoma.

PMID- 18812910
TI  - Bone mineral density in children with neurofibromatosis type 1.

PMID- 18812911
TI  - Thoracolumbar spinal deformity: evaluation and treatment. Foreword.

PMID- 18812912
TI  - Iatrogenic spinal deformity.
AB  - Patients with postoperative spinal deformities are being identified with
      increasing frequency as the number of instrumented spinal operations increases.
      Thus, it is important for the neurosurgeon to understand ways to minimize
      postoperative deformity and to understand its operative and nonoperative
      management. A variety of intra- and postoperative risk factors have been
      associated with postoperative deformity, including patient age, operative
      positioning, preoperative medical condition, and the use of prior radiation
      therapy. The evaluation of all patients who have been suspected of iatrogenic
      deformity should include a detailed physical examination, plain x-rays, and
      computed tomographic or magnetic resonance imaging, depending on the condition.
      Conservative therapy includes physical therapy and pain control, which may be
      effective in some patients. However, patients with flat-back syndrome typically
      require reoperation. A wide variety of reoperative procedures may be performed,
      depending on the area of the pathological deformity, extent of disease, and
      patient condition.

PMID- 18812913
TI  - Delayed posttraumatic thoracolumbar spinal deformities: diagnosis and management.
AB  - Approximately 50,000 traumatic injuries resulting in fractures of the bony spinal
      column occur annually in the United States. Although some of these lesions are
      clearly unstable and mandate urgent surgical treatment for stabilization, less
      severe injuries may be managed initially with bracing and serial imaging to
      evaluate bony healing and alignment. A proportion of these injuries will require
      delayed surgical intervention to correct a posttraumatic deformity. In addition,
      inadequate or ineffective acute spinal stabilization can also result in the
      progression of delayed spinal deformities. The management of these lesions is
      frequently complicated by scarring in the body cavities from the inciting trauma
      or any subsequent surgical interventions, epidural scar formation and spinal cord
      tethering, solid fusion into the deformed state, medical comorbidities associated
      with paralysis, and compromised spinal cord function. With these factors in mind,
      surgical management of these frequently kyphotic deformities can be performed via
      a posterior approach with osteotomies or a combined anterior approach and
      posterior procedures.

PMID- 18812914
TI  - Bracing for scoliosis.
AB  - Bracing is the oldest treatment known for scoliotic spinal deformity. The
      relative advantages to the use of bracing have been directly related to the
      etiology of the deformity and the flexibility of the spine at the time that a
      decision is made regarding the use of a brace. In skeletally immature patients
      with adolescent idiopathic scoliosis, the advantages to bracing are clear. In
      many instances, prompt recognition and appropriate bracing can arrest the
      progression of this form of deformity, and, in so doing, the need for any surgery
      may be avoided completely. On the other hand, in skeletally mature adult
      deformity patients, bracing has almost no proven role in affecting the natural
      history of the disease. Likewise, infantile and congenital scoliosis routinely
      requires surgical correction to prevent curve progression. Lastly, although many
      surgeons use bracing in the postoperative management of patients with spinal
      deformity, the benefits of postoperative bracing remain debatable. By far, the
      best indication for bracing is treatment of the skeletally immature adolescent
      patient with an idiopathic flexible curve of less than 45 degrees magnitude.

PMID- 18812915
TI  - Segmental spinal instrumentation in the management of scoliosis.
AB  - Spinal instrumentation for the correction of spinal deformity began with
      Harrington and his rod system. The use of the Harrington rods was limited,
      however, because of the need for long-segment instrumentation, distraction, and
      the potential for hood dislodgment and construct failure. Luque subsequently
      introduced the next generation of spinal fixation techniques via the concept of
      segmental instrumentation; his use of sublaminar wires allowed the construct to
      be fixated to the spine at every level. This arrangement allowed greater control
      over correction of spinal deformities and significantly lessened the incidence of
      hardware dislodgment. Modern instrumentation systems, including the use of
      pedicle screws, permit even greater control of the spine in multiple planes
      during deformity correction. Newer strategies have decreased the incidence of
      neurological injury during implant application and provide greater stability. A
      review of segmental fixation, including surgical techniques, is provided in this
      article.

PMID- 18812916
TI  - Anterior-only approaches to scoliosis.
AB  - Scoliosis is a three-dimensional spinal deformity for which surgery may be
      indicated when patients experience severe pain, curve progression, or progressive
      disability. Operative treatment has conventionally involved extensive posterior
      stabilization, either alone or in combination with anterior release procedures.
      Anterior-only approaches have a more limited role, but they should be considered
      in the appropriate setting when addressing this disease. Some advantages of
      anterior-only approaches to scoliosis include greater corrective ability with a
      greater fusion rate while mandating fewer motion segments to be involved in the
      instrumented construct. Preventing denervation of the posterior paraspinal
      musculature is also desirable and is inherently provided for by the anterior
      approach. Disadvantages include pulmonary morbidity associated with violating the
      thoracic cavity, as well as post-thoracotomy chronic pain. There are also
      limitations in the indications for which anterior-only surgery can be performed,
      and these will be discussed along with treatment options. Technological advances,
      including minimally invasive thoracic access as well as evolving instrumentation,
      may minimize the stated disadvantages and expand the scope of scoliosis cases
      that may be treated by anterior-only approaches. Hence, the enhanced corrective
      ability and biomechanical advantages of the anterior column can be used in the
      treatment of these patients. Although the indications for anterior-only
      strategies in scoliosis remain limited, such operations should be considered in
      the appropriate setting when addressing spinal deformity.

PMID- 18812917
TI  - Rod derotation techniques for thoracolumbar spinal deformity.
AB  - OBJECTIVE: The operative correction of scoliosis requires multiple intraoperative
      techniques and tools to achieve an adequate result. Frequently, multiple methods
      are used to accomplish this, such as rod cantilever techniques, in situ bending,
      Smith-Petersen and pedicle subtraction osteotomies, closed reduction methods, and
      rod derotation techniques. Rod derotation techniques will be reviewed and
      discussed in this article. METHODS: A review of the available literature on
      anterior and posterior rod derotation is performed with a case example of the
      authors' experience utilizing this technique. RESULTS: Rod derotation is one
      technique that can transform a pathological scoliotic curve to normal
      physiological kyphosis or lordosis by simply rotating a rod intraoperatively.
      CONCLUSION: In this article, the authors present rod derotation as a valuable
      technique in the surgical arsenal for the treatment of scoliosis, including a
      discussion of the technique and its limitations.

PMID- 18812918
TI  - Rod cantilever techniques.
AB  - Cantilever beam fixation techniques have a broad application in spine surgery,
      including the treatment of thoracolumbar spinal deformities. There are
      traditionally three cantilever beam fixation types described: fixed moment arm,
      nonfixed moment arm, and applied moment arm. In practice, however, most
      constructs are applied in a hybrid fashion. The basic tenets of cantilever beam
      fixation are provided in this article.

PMID- 18812919
TI  - Classification systems for adolescent and adult scoliosis.
AB  - OBJECTIVE: To review current classification systems for adolescent and adult
      scoliosis. METHODS: The literature was reviewed in reference to scoliosis
      classification systems for adolescent and adult scoliosis. RESULTS: There are
      multiple classification systems for scoliosis. Classification of scoliosis is
      dependent on patient age, spinal abnormality, scoliotic curve, and global spinal
      alignment. To date, classification systems have focused predominantly on
      adolescent idiopathic scoliosis or adult/degenerative scoliosis; a single
      classification system evaluating scoliotic deformities of different ages and
      spinal abnormalities has not been identified. CONCLUSION: The importance of
      scoliosis classification schemes lies in their ability to standardize
      communication among health care providers. With regard to the classification of
      adolescent scoliosis, the Lenke system has addressed many of the significant
      limitations of the King system and is now the standard classification scheme.
      Classification schemes for adult scoliosis have been reported only recently, and
      each offers specific advantages (the simple pathogenesis-based system of Aebi,
      the strong clinical relevance of the Schwab system, and the richly descriptive
      Scoliosis Research Society system). This article highlights the salient features
      of currently used scoliosis classification systems.

PMID- 18812920
TI  - Smith-Petersen osteotomy in thoracolumbar deformity surgery.
AB  - OBJECTIVE: To describe the technique and indications of a Smith-Petersen
      osteotomy in spinal deformity surgery. METHODS: Pertinent literature was reviewed
      to describe the indications and reported complications of this corrective
      technique. RESULTS: The operative nuances of the technique are described.
      CONCLUSION: A Smith-Petersen osteotomy is a safe and effective surgical technique
      to obtain correction of spinal deformity in both the sagittal and coronal planes.

PMID- 18812921
TI  - Pedicle subtraction osteotomy.
AB  - OBJECTIVE: Pedicle subtraction osteotomy (PSO) is an effective tool for the
      correction of fixed sagittal plane deformity. However, there is potentially
      significant perioperative morbidity associated with this technique. We report our
      perioperative morbidity rate in recently performed PSO cases treated with our
      present surgical, anesthetic, and monitoring techniques and discuss complication
      avoidance strategies. METHODS: We conducted a retrospective study of 10 patients
      (mean age, 56 yr; range, 7-77 yr) undergoing thoracolumbar PSO at a single
      institution in the past 3 years. Two patients underwent PSO at T12, seven
      patients underwent PSO at L3, and one patient underwent PSO at L2. Eight of the
      patients had undergone at least one previous spine surgery in the region of the
      PSO, and nine of the patients had comorbidities that increased their surgical
      risk stratification. We identified all causes of perioperative morbidity.
      RESULTS: We classified perioperative complications into two categories:
      intraoperative and early postoperative. Intraoperative complications included
      dural tears in two patients, cardiovascular instability in one patient, and
      coagulopathy in two patients. Early postoperative complications included
      neurological deficit (one patient), wound infection (two patients), urinary tract
      infection (one patient), and delirium (two patients). All patients recovered
      fully from these complications. There was no mortality in this series.
      CONCLUSION: In this series, most patients undergoing PSO had multiple previous
      spine surgeries and comorbidities. The risk of perioperative morbidity for
      revision cases undergoing PSO was in excess of 50%. We discuss complication
      avoidance strategies.

PMID- 18812922
TI  - Vertebral column resection for rigid spinal deformity.
AB  - OBJECTIVE: Vertebral column resection (VCR) is a surgical technique that may be
      applied for correction of moderate to severe spinal deformities, including those
      with large rigid curves, fixed trunk translation, or asymmetry between the length
      of the convex and concave column of the deformity. This article reviews the VCR
      technique as it relates to correction of rigid spinal deformity, including case
      examples to illustrate its application. METHODS: The literature was reviewed in
      reference to the use of VCR for correction of rigid spinal deformity. RESULTS:
      VCR involves complete resection of one or more vertebral segments using either
      combined anterior and posterior approaches or a posterior-only approach and
      enables significant deformity correction in all three dimensions. Herein, we
      provide description of the indications, preoperative planning, surgical
      techniques, complication avoidance, postoperative management, and case examples
      for VCR. CONCLUSION: VCR enables significant correction of rigid spinal
      deformities in cases in which less aggressive approaches are not adequate.

PMID- 18812923
TI  - Long-segment spinal fixation using pelvic screws.
AB  - OBJECTIVE: Long spinal constructs that extend to the sacrum place added stress on
      sacral screws. To prevent premature loosening of sacral fixation in these cases,
      the addition of pelvic screw (iliac screw) fixation has gained in popularity.
      Pelvic screw fixation has also been used in cases where sacral screw fixation is
      not possible (e.g., in sacral tumors). Pelvic screw fixation is more
      straightforward than prior pelvic rod fixation techniques (e.g., the Galveston
      technique). We describe our technique for pelvic screw fixation and review our
      experience with this technique. METHODS: Twenty consecutive patients who
      underwent spinal-pelvic fixation were followed over a 3-year period (2004-2007).
      The patient population consisted of 11 men and 9 women with an average age of
      58.8 years. Indications for spinal-pelvic fixation in this series included
      kyphoscoliosis, lumbosacral pseudoarthrosis, sacral fractures, lumbosacral
      spondylolisthesis, sacral tumors, and lumbar osteomyelitic fractures.
      Radiographic outcomes were assessed using flexion-extension x-rays and computed
      tomographic scans. Clinical outcomes were assessed using Odom's criteria and
      modified Prolo scale. RESULTS: One patient was lost to radiographic follow-up.
      One patient died after surgery. The mean follow-up for the remaining patients was
      13 months (range, 1-21 mo). Odom's outcomes were rated as good to excellent in 11
      (58%), fair in 7 (37%), and poor in 1 (5%) (one patient died). Preoperative and
      postoperative modified Prolo scores were 10.4 and 12.9, respectively (mean
      improvement, 2.5). Radiographic fusion across the lumbosacral junction was
      obtained in 16 (89%) of the 18 patients with follow-up. One patient required
      revision of a pelvic screw. There was one infection requiring explantation of
      hardware. CONCLUSION: Pelvic screw fixation is a safe and effective technique
      that provides added structural support to S1 screws in long-segment spinal
      fusions. Furthermore, pelvic screw fixation provides a distal point of fixation
      in cases where sacral screw fixation is not possible. The use of polyaxial screws
      and connectors makes this technique easier than Galveston rod fixation of the
      pelvis.

PMID- 18812924
TI  - Minimally invasive anterolateral approaches for the treatment of back pain and
      adult degenerative deformity.
AB  - Minimally invasive and interbody and instrumented fusion techniques are
      increasingly being used for the treatment of adult degenerative disc disease,
      stenosis, and deformity of the lumbar spine. Advocates of minimal access spinal
      approaches list certain advantages over open procedures, including decreased
      postoperative pain and narcotic requirements, shorter hospital stays, less blood
      loss, and smaller incisions. The minimally invasive anterolateral approach allows
      access to the lumbar spine through the retroperitoneal space. We report on the
      short-term clinical and radiographic outcomes in four patients with mid to high
      lumbar coronal deformities treated at our institution with the anterolateral
      transpsoas minimally invasive approach. The primary presentation of these
      patients was back and leg pain. All patients showed improvement in their
      preoperative symptoms and solid arthrodesis at 6 months. Independent nonbiased
      patient pain analysis was also performed. Mean follow-up was 10 months (standard
      deviation, 1.4 mo), and mean hospital stay was 3.5 days (standard deviation, 1.9
      d). One patient had additional posterior segmental instrumentation placed. Mean
      Cobb angles in the coronal plane were 28.5 degrees preoperatively and 18.3
      degrees postoperatively (P < 0.05). We also present a historical perspective on
      retroperitoneal spine surgery, a regional anatomic description of the lumbosacral
      plexus and surrounding structures, and a description of the surgical technique as
      related to treatment of lumbar deformity.

PMID- 18812925
TI  - Minimally invasive posterior fixation.
AB  - Significant advances have been made in the contemporary management of
      thoracolumbar spinal deformities, including improved segmental bony fixation,
      techniques for osteotomy, and mechanically powerful reduction maneuvers, which
      now allow the spinal surgeon to correct severe, complex, and rigid spinal
      deformities. However, one of the major limitations of surgical intervention has
      been the high complication rates associated with these surgical endeavors. Much
      of the morbidity associated with posterior deformity surgery relates to the
      extensive soft tissue destruction necessary to gain access to multiple segments
      of the axial skeleton. The open exposures for long-segment fixation result in
      additional blood loss, increased rates of infection, and prolonged immobilization
      caused by postoperative pain. Minimally invasive techniques attempt to overcome
      these drawbacks of the open exposures, and this report reviews preliminary
      experience in treating spinal deformities with long-segment minimally invasive
      internal fixation.

PMID- 18812926
TI  - Thoracolumbar spinal deformity: evaluation and treatment. Prefaces.

PMID- 18812927
TI  - Minimally invasive posterior osteotomies.
AB  - OBJECTIVE: Surgery for thoracolumbar deformity can lead to significant muscle
      injury, excessive blood loss, and severe postoperative pain. The aim of the
      following studies was to determine the feasibility of minimally invasive
      posterior thoracic corpectomy and thoracolumbar osteotomy techniques for
      deformity in human cadavers and select clinical cases. METHODS: Human cadaveric
      specimens were procured for thoracic corpectomy and Smith-Petersen and pedicle
      subtraction osteotomy using a minimally invasive approach. Post-procedural
      computed tomography was used to assess the degree of decompression following
      corpectomy and the extent of bone resection after osteotomy. Pre and post
      osteotomy closure Cobb angles were measured to evaluate the degree of correction
      achieved. RESULTS: The minimally invasive lateral extracavitary approach for
      thoracic corpectomy provided adequate exposure and allowed excellent spinal canal
      decompression while minimizing tissue disruption. Nearly complete osteotomies of
      both types could be achieved through a tubular retractor with a modest change in
      Cobb angle. CONCLUSION: These techniques may play a role in deformity surgery for
      select cases with further technological advancements.

PMID- 18812928
TI  - Principles of growth modulation in the treatment of scoliotic deformities.
AB  - Intraoperative manipulation to correct scoliotic deformities relies upon spinal
      instrumentation for stabilization and fusion. However, novel strategies and
      innovative implant biotechnologies have emerged, applying natural growth and
      elongation of the immature spine for the treatment of scoliosis in young
      patients. In this work, we review the principles of growth modulation and the
      Hueter-Volkmann law as it applies to experimental models of scoliosis formation
      and correction. Current implant technologies, including shape memory alloy
      vertebral staples, growing rods, and vertical expandable titanium prosthetic
      ribs, are explored, with regards to implant design, surgical techniques, and
      clinical investigations. An exciting area of spinal implant technology is now
      becoming available to expand the surgical armamentarium for treating severe
      scoliotic deformity in young patients.

PMID- 18812929
TI  - Genetics of scoliosis.
AB  - Scoliosis is one of the oldest known deformities of humankind; however, the cause
      still remains ill defined. Although there is a lack of uniform agreement on the
      inclusion criteria for the definition of scoliosis, most investigators agree that
      a coronal curve must measure at least 10 degrees for the patient to be considered
      to have scoliosis. A broad range of articles were reviewed and the relevant
      publications that contributed information regarding the genetics of scoliosis
      were selected for inclusion in this report. Based on family pedigree and genetic
      studies, the proposed pattern of inheritance for markers of scoliosis are
      expected to be autosomal dominant, X-linked, multigene, or multifactorial. This
      is further complicated by locus heterogeneity, allele heterogeneity, and carrier
      states found in normal individuals. Although none of these modes of inheritance
      has been definitively proven, it appears that a multifactorial mode of
      inheritance with variable penetrance is the most likely method.

PMID- 18812930
TI  - Spinal deformity: a new classification derived from neutral upright spinal
      alignment measurements in asymptomatic juvenile, adolescent, adult, and geriatric
      individuals.
AB  - OBJECTIVE: In this literature review, the authors analyze data from previously
      published studies that evaluated neutral upright spinal alignment (NUSA) from the
      occiput to the pelvis in asymptomatic individuals. Based on the data for NUSA in
      asymptomatic volunteers, a new classification is proposed for spinal deformity.
      METHODS: A review of the English literature was conducted to identify studies
      evaluating NUSA from the occiput to the pelvis in asymptomatic juvenile,
      adolescent, adult, and geriatric volunteers. From the literature review, 17
      angles and displacements were selected to depict neutral upright coronal and
      axial spinal alignment, and 21 angles and displacements were selected to depict
      neutral upright sagittal spinal alignment. Pooled estimates of the mean and
      variance were calculated for the angles and displacements from the articles that
      met inclusion criteria. A new classification of spinal deformity was then
      developed based on age-dependent NUSA; spinal abnormality; deformity curve
      location, pattern, magnitude, and flexibility; and global spinal alignment.
      RESULTS: Despite a wide variation in the regional curves from the occiput to the
      pelvis in asymptomatic volunteers, global spinal alignment is maintained in a
      narrow range for preservation of horizontal gaze and balance of the spine over
      the pelvis and femoral heads. CONCLUSION: A new classification of spinal
      deformity is proposed that provides a structure for defining deformity of all
      patient ages and spinal abnormalities.

PMID- 18812931
TI  - Radiographic measurement techniques.
AB  - The evaluation and treatment of spinal deformities begins with the accurate
      measurement of appropriate spinal parameters. The surgeon must ensure that the
      patient is positioned properly for all necessary x-ray scans and that the proper
      studies are completed. The relevant measurements must be identified and recorded
      for each study. Understanding the proper measurement techniques will increase the
      accuracy and reliability of the measurements. From these precise measurements the
      surgeon can begin to determine key characteristics of the deformity and develop
      an appropriate treatment plan.

PMID- 18812932
TI  - Noninvasive measurement and screening techniques for spinal deformities.
AB  - OBJECTIVE: Spinal deformities are caused by a heterogeneous collection of disease
      processes. The progression of the scoliotic curve can vary depending on the
      individual patient, as well as the curve etiology. Noninvasive measurement
      techniques have been developed to obtain a baseline in addition to record curve
      progression. METHODS: We designed our study based on a comprehensive literature
      review and clinical experience. A systematic review of Medline for articles
      related to spinal deformities (scoliosis) and screening techniques was conducted
      up to and including those journal articles published in March 2007. RESULTS:
      There are numerous noninvasive modalities available to assess curve progression.
      CONCLUSION: The use of a detailed physical examination, serial examinations, and
      radiographic means serve well to document curve presence and monitor progression.

PMID- 18812933
TI  - The history of spinal deformity.
AB  - Spinal deformity is the oldest disease known to humankind. The first record of
      correction of spinal deformity was documented in an Indian religious mythological
      book written between 3500 BC and 1800 BC. Initially, all spinal deformities were
      treated with the use of braces, traction, or casts. Hippocrates was the first
      physician to treat spinal deformities by using axial traction combined with
      direct pressure. Galen specifically described the anatomy of the spine and spinal
      nerves. The treatment of spinal deformity was greatly improved by the development
      of radiographic imaging by Roentgen. After x-rays became available, spinal
      fusions began to be used to treat scoliotic curves. Hibbs described the first
      spinal fusion to stabilize a deformed tuberculous spine. Soon enough, other
      investigators began to report on a variety of surgical techniques used to treat
      spinal deformity. Surgical approaches from both the posterior and anterior
      directions were developed and modified in an attempt to achieve durable curve
      corrections. Harrington's distraction rod system was a major innovation in
      providing a method to improve coronal plane deformity. Luque introduced segmental
      instrumentation, which opened up the era of modern surgical techniques for spinal
      deformity. This concept allowed surgeons to begin to achieve three-dimensional
      corrections by respecting both the sagittal and coronal curves simultaneously.
      The introduction of pedicle screws, throughout the thoracolumbar spine, has
      increased the ability of surgeons to achieve greater degrees of curve correction
      than had previously been possible. The history of spinal deformity is still
      maturing as newer procedures continue to be performed on a daily basis.

PMID- 18812934
TI  - Decision making in pediatric spinal deformity.
AB  - OBJECTIVE: To review the concepts involved in the decision-making process for
      management of pediatric patients with spinal deformity. METHODS: The literature
      was reviewed in reference to pediatric deformity evaluation and management.
      RESULTS: Pediatric spinal deformity includes a broad range of disorders with
      differing causes, natural histories, and treatments. Appropriate categorization
      of pediatric deformities is an important first step in the clinical decision
      making process. An understanding of both nonoperative and operative treatment
      modalities and their indications is requisite to providing treatment for
      pediatric patients with spinal deformity. The primary nonoperative treatment
      modalities include bracing and casting, and the primary operative treatments
      include nonfusion instrumentation and fusion with or without instrumentation. In
      this article, we provide a review of pediatric spinal deformity classification
      and an overview of general treatment principles. CONCLUSION: The decision-making
      process in pediatric deformity begins with appropriate diagnosis and
      classification of the deformity. Treatment decisions, both nonoperative and
      operative, are often predicated on the basis of the age of the patient and the
      natural history of the disorder.

PMID- 18812935
TI  - Decision making in adult deformity.
AB  - Spinal deformity affects adults and adolescents in different ways. Adult
      deformity patients are skeletally mature and tend to have relatively fixed
      curves, whereas adolescent patients are skeletally immature with flexible curves.
      As a result, adult patients typically present with back pain and neurological
      concerns, whereas adolescents present with cosmetic complaints. The goals of
      surgery on the adult deformity patient are to treat pain and relieve neurological
      problems while maintaining or achieving three-dimensional balance. The absolute
      degree of coronal curve correction in an adult deformity patient is less
      important than maintaining good sagittal balance. Issues that must be addressed
      in the preoperative decision-making process include the approach to the surgery,
      the timing of the surgery, and the location of the end of the construct. Twenty
      years ago, anteroposterior surgery was the most common procedure used for adults
      with fixed curves; however, recent advances in technology and techniques have led
      to more frequent use of purely posterior approaches. The posterior approach
      allows for greater curve correction owing to two major advances in the surgical
      method: osteotomy techniques, which release fixed deformities, and pedicle screw
      instrumentation in the thoracolumbar spine, which achieves greater curve
      correction with fewer levels of fixation. The optimal timing of surgery and the
      levels to be treated remain open to debate. Each adult patient's treatment must
      be individualized to achieve the best coronal correction possible while
      maintaining sagittal balance to preserve the three-dimensional balance of the
      spine.

PMID- 18812936
TI  - Congenital thoracolumbar spine deformities.
AB  - Congenital thoracolumbar spinal deformities are a common and frequent reason for
      referral to spine surgeons. Neurosurgeons also treat many neurological diagnoses
      which may result in a progressive spinal deformity, such as scoliosis. Here we
      review a variety of congenital anomalies and address the maldevelopments
      associated with each, as well as the appropriate evaluation of such patients
      including nonoperative and operative approaches. Advances in the field of spinal
      deformity correction now allow us to better treat individuals with these types of
      deformities. It is important for the practicing neurosurgeon to be knowledgeable
      of surgical and nonsurgical treatments of patients with congenital thoracolumbar
      spinal deformities in order to better understand which patients will ultimately
      progress and necessitate surgical treatment.

PMID- 18812937
TI  - Idiopathic scoliosis.
AB  - Idiopathic scoliosis (IS) most commonly develops during adolescence, but may
      present at any age from infancy through adulthood. Patients with IS are evaluated
      clinically and radiographically to determine whether the deformity is, in fact,
      idiopathic, to elucidate any symptoms related to the scoliosis, and to
      characterize the deformity itself. In patients who have not yet reached skeletal
      maturity, the treatment of IS is often prophylactic, with the aim of preventing
      the curve from reaching a magnitude that would make continued progression in
      adulthood likely. Adult patients with IS are most frequently treated because of
      symptoms, usually back or leg pain. IS is typically treated with anterior or
      posterior spinal fusion; treatment of very young patients is complicated by the
      need to allow growth to continue while controlling the scoliosis.

PMID- 18812938
TI  - Adult degenerative scoliosis: a review.
AB  - OBJECTIVE: To review and define principles and features of treatment for adult
      degenerative scoliosis, the most common cause of adult spinal deformities. STUDY
      DESIGN: We conducted a comprehensive review of the literature and our clinical
      experience. METHODS: A systematic review of Medline was conducted, including
      journal articles published in March 2007 and before. We searched for articles
      related to adult spinal deformities (scoliosis) and treatments. CONCLUSION:
      Degenerative scoliosis is a complex disorder. The primary surgical aims are to
      decompress the neural elements, normalize both sagittal balance and coronal and
      rotational deformity, fixate to the sacrum/ilium when appropriate, and optimize
      conditions for osteogenesis and fusion.

PMID- 18812940
TI  - Rupture of a pseudoaneurysm of the posterior meningeal artery at its anomalous
      origin from the posteroinferior cerebellar artery: case report.
AB  - OBJECTIVE: The posterior meningeal artery (PMA) normally arises from the
      vertebral artery; however, its origin varies considerably as the result of its
      embryological development. This gains clinical significance when associated with
      vascular pathology. CLINICAL PRESENTATION: A 65-year-old man presented to his
      local hospital with a sudden-onset, severe headache. Computed tomography of the
      head revealed diffuse subarachnoid hemorrhage, mostly in the left posterior
      fossa. A computed tomographic angiogram demonstrated an anomalous origin of the
      PMA from the posteroinferior cerebellar artery (PICA). Cerebral angiography
      showed the PICA to be enlarged, with a reduced caliber at the takeoff of the PMA,
      which is consistent with possible dissection. INTERVENTION: The patient was taken
      to the operating room for trapping of the dissecting segment of the PMA. A clip
      was placed across the PMA at its origin from the PICA, and the vessel was
      coagulated and transected. The PICA was wrapped in muslin gauze. CONCLUSION: The
      variable origin of the PMA and PICA may be the result of the persistence of
      embryological anastomoses between the arteries, with regression of the normal
      channel. Physical stress at the junction of the anomalous PMA and the PICA may
      have contributed to the abnormality of the PMA, consistent with possible
      dissection. Because the PMA has multiple anastomoses with the arteries of the
      falx cerebri, the proximal PMA may be occluded with no compromise to its vascular
      territory.

PMID- 18812941
TI  - The development of ring-shaped contrast enhancement in a case of cerebellar
      dysembryoplastic neuroepithelial tumor: case report.
AB  - OBJECTIVE: Dysembryoplastic neuroepithelial tumor (DNT) occurs rarely in the
      cerebellum. We describe a rare case of cerebellar DNT that developed contrast
      enhancement after long-term observation and discuss the underlying mechanism and
      clinical relevance of this unusual phenomenon. CLINICAL PRESENTATION: A 34-year
      old woman with known cystic cerebellar lesions presented with increased frequency
      of vertigo and new onset of truncal ataxia. Magnetic resonance imaging revealed
      new contrast enhancement in the dominant cystic lesion of the cerebellar vermis
      without any change in size and shape or evidence of edema. INTERVENTION: The
      lesions were resected under magnetic resonance imaging guidance. Histological
      assessment revealed populations of small, round cells in a microcystic background
      containing "floating" neurons, diagnostic of DNT. Microvascular proliferation and
      pigmented neurons were also present. CONCLUSION: This is the first report of the
      development of contrast enhancement in a previously nonenhancing case of
      cerebellar DNT. The acquisition of ring-shaped contrast enhancement may be
      associated with microvascular proliferation, but otherwise no evidence of
      malignant progression. In addition, this case presents the novel pathological
      finding of pigmented neurons in DNT.

PMID- 18812942
TI  - Intramedullary spinal cord metastasis from bladder carcinoma: case report.
AB  - OBJECTIVE: Intramedullary spinal cord metastases are rare complications of
      systemic cancer. Although the majority of these metastases spread from lung
      cancer, they have been seen to arise from a variety of other primary sources. The
      authors report the second known case of an intramedullary spinal cord metastatic
      lesion arising from primary bladder carcinoma. CLINICAL PRESENTATION: A 74-year
      old man presented with an 8-day history of rapidly progressive Brown-Sequard
      syndrome, with weakness in his left lower extremity and decreased pain and
      temperature sensation in his right lower extremity. The patient's history was
      significant for high-grade urothelial carcinoma that had been treated 6 months
      earlier with radical cystectomy. A magnetic resonance imaging scan showed an
      enhancing intramedullary lesion at T1-T2. INTERVENTION: The patient underwent
      laminectomies, and removal of his intramedullary lesion was attempted.
      Intraoperative pathology revealed that the lesion was metastatic in nature, and
      the decision was made to perform a subtotal resection. Pathology later confirmed
      that the lesion was consistent with a less differentiated form of his bladder
      primary. Postoperatively, the patient experienced minimal improvement in his
      symptoms, and he was subsequently treated with fractionated external beam
      radiotherapy. The patient died 7 weeks after undergoing surgery for his spinal
      cord lesion. CONCLUSION: The occurrence of metastatic primary bladder cancer in
      the intramedullary spinal cord has been reported in the literature only once
      previously. Despite the lack of similar cases, the acute onset of Brown-Sequard
      syndrome was highly suggestive of a metastatic lesion. A review of relevant
      literature is provided.

PMID- 18812943
TI  - Intra-abdominal vascular injury during trocar-assisted ventriculoperitoneal
      shunting: case report.
AB  - OBJECTIVE: Laparoscopic trocar injury is a relatively well-described complication
      of cholecystectomies and gynecological procedures. However, this type of injury
      has not been reported in association with adult neurological surgery. To increase
      awareness of this very serious risk, we report a case of intra-abdominal vascular
      injury during a shunt procedure involved with a common neurosurgical procedure.
      CLINICAL PRESENTATION: A 76-year-old man with no previous abdominal surgical
      history presented with probable normal pressure hydrocephalus. INTERVENTION:
      After an appropriate preoperative workup confirming probable normal pressure
      hydrocephalus, the patient consented to placement of a ventriculoperitoneal shunt
      with a programmable valve. During placement of the distal catheter using an
      abdominal trocar, the aorta was punctured inadvertently, necessitating emergency
      laparotomy for vascular repair. CONCLUSION: An abdominal trocar should be used
      with caution in ventriculoperitoneal shunt surgery. Even with meticulous
      technique, vascular injury can occur with any trocar-based abdominal procedure.
      The neurosurgeon who uses this technique must be prepared to initiate emergent
      vascular access and repair, with a vascular surgery team available should such an
      injury occur. Alternatively, open placement of peritoneal catheters avoids blind
      peritoneal instrumentation and is an effective method for minimizing potentially
      catastrophic vascular injuries.

PMID- 18812944
TI  - Chiari I malformation as a cause of trigeminal neuralgia: case report.
AB  - OBJECTIVE: Trigeminal neuralgia (TN) is usually associated with vascular
      compression of the trigeminal nerve, but some cases are associated with central
      lesions such as tumors, aneurysms, or arteriovenous malformations. In this
      article, we report the 19th case of TN associated with Chiari I malformation and
      review clinical outcomes and pathophysiology. CLINICAL PRESENTATION: A 63-year
      old right-handed man initially presented in 1993 with left-sided lancinating
      facial pain in the V2 distribution of the trigeminal nerve; the pain was
      triggered by certain movements, tactile stimulation, or a hot shower. Magnetic
      resonance imaging revealed a Chiari I malformation associated with a syrinx from
      C1 to C3. INTERVENTION: The patient underwent uncomplicated suboccipital
      craniectomy, C1 laminectomy, and duraplasty for Chiari decompression.
      Postoperatively, his pain resolved over a period of 1 year. CONCLUSION: Chiari I
      malformation has been found to be associated with TN in 19 cases in the English
      language literature. In patients refractory to medical treatment, suboccipital
      decompression leads to resolution of pain in about two-thirds of patients.
      Potential mechanisms for the pathogenesis of TN in the setting of Chiari I
      malformation are discussed. Chiari I malformation is important to consider as a
      rare cause of TN that responds to surgical therapy.

PMID- 18812945
TI  - Intracranial placement of a new, compliant guide catheter: technical note.
AB  - OBJECTIVE: We describe our initial experience with the use of a novel, compliant
      guide catheter designed for placement within the cranial vasculature in a series
      of seven patients who were treated for various intracranial pathologies. CLINICAL
      PRESENTATION: Seven patients were deemed to have either tortuous supra-aortic,
      intracranial, and/or extracranial vasculature or to require additional
      microcatheter support as the result of lesion location. INTERVENTION: The
      patients were treated, in part, with the 6-French Neuron delivery catheter
      (Penumbra, Inc., San Leandro, CA) at the authors' two institutions. The guide
      catheter was positioned in various distal locations within the intracranial
      internal carotid artery or external carotid artery. Three patients were treated
      for unruptured intracranial aneurysms, 2 patients for intracranial
      atherosclerosis, 1 patient for an arteriovenous malformation, and 1 patient for a
      pseudoaneurysm. CONCLUSION: All lesions were successfully treated through a
      microcatheter advanced in a coaxial fashion through the guide catheter. There
      were no complications related to the positioning of the catheter. Distal intra-
      or extracranial placement of a specially designed, compliant guide catheter can
      be performed safely and may improve access and microcatheter stability in
      patients with tortuous vessels or difficult-to-reach lesions.

PMID- 18812950
TI  - Mesenchymal stem cell and gene therapies for spinal fusion.
AB  - THE IDEAL GRAFT material to promote spinal fusion should possess osteoconductive,
      osteoinductive, and osteogenic properties. Although autogenous bone graft has all
      three qualities and is the standard for comparison, research has focused on
      finding alternatives that have similar efficacy but not the morbidities
      associated with graft donor sites. Efforts have focused on various
      osteoconductive scaffolds and introduction of osteoinductive proteins, including
      bone morphogenetic protein. Recently, interest in using osteoprogenitor cells, or
      osteogenesis, for spinal fusion has increased. Bone marrow aspiration allows the
      introduction of mesenchymal stem cells and ultimately osteoblasts to promote
      fusion. Preclinical studies suggest that the addition of osteoprogenitor cells to
      various osteoconductive materials results in a fusion rate similar to that of
      autograft. There is growing recognition that local gene therapy has the benefit
      of delivering therapeutic genes that encode novel osteoinductive proteins. Gene
      delivery offers an alternative to local implantation of recombinant protein,
      which typically requires high doses of the protein to result in a sufficient
      osteoinductive response. The findings of animal studies demonstrate that gene
      therapy results in sustained and regulated production of desired osteoinductive
      proteins and is efficacious in promoting spinal fusion; however, before treatment
      in humans can be undertaken, obstacles such as the safety profile, host immune
      response, transfection rates with insufficient transgene expression, and
      imprecise control of the timing of transgene expression must be overcome. In this
      review, the authors summarize the latest research efforts under way to promote
      spinal fusion with osteoprogenitor cells and gene therapy and discuss the
      clinical implications of these treatments.

PMID- 18812951
TI  - Challenging traditional beliefs: microsurgery for arteriovenous malformations of
      the basal ganglia and thalamus.
AB  - OBJECTIVE: Arteriovenous malformations of the basal ganglia and thalamus are
      often managed with radiosurgery or observation, without consideration of
      microsurgery. Given the devastating effects of hemorrhage from these lesions, the
      accumulating evidence that they bleed more frequently than their lobar
      counterparts should prompt more creative thinking regarding their management.
      METHODS: A review of the endovascular, microsurgical, and radiosurgical
      literature for arteriovenous malformations of the basal ganglia and thalamus was
      performed, with close attention to surgical approaches, obliteration rates, and
      procedure-related complications. RESULTS: A complete resection rate of 91% and a
      mortality rate of 2.4% were found across surgical series of these lesions. These
      contrast with a 69% rate of complete obliteration and a 5.3% mortality rate (from
      latency-period hemorrhage) found when compiling results across the radiosurgical
      literature. CONCLUSION: Given an appropriate surgical corridor of access, often
      afforded by incident hemorrhage, arteriovenous malformations of the basal ganglia
      and thalamus should be considered for microsurgical extirpation with preoperative
      embolization. In experienced hands, this approach presents an expeditious and
      definitive opportunity to eliminate the risk of subsequent hemorrhage and
      resultant morbidity and mortality.

PMID- 18812952
TI  - Intraoperative magnetic resonance imaging at 3-T using a dual independent
      operating room-magnetic resonance imaging suite: development, feasibility,
      safety, and preliminary experience.
AB  - OBJECTIVE: A twin neurosurgical magnetic resonance imaging (MRI) suite with 3-T
      intraoperative MRI (iMRI) was developed to be available to neurosurgeons for iMRI
      and for independent use by radiologists. METHODS: The suite was designed with one
      area dedicated to neurosurgery and the other to performing MRI under surgical
      conditions (sterility and anesthesia). The operating table is motorized, enabling
      transfer of the patient into the MRI system. These two areas can function
      independently, allowing the MRI area to be used for nonsurgical cases. We report
      the findings from the first 21 patients to undergo scheduled neurosurgery with
      iMRI in this suite (average age, 51 +/- 24 yr; intracranial tumor, 18 patients;
      epilepsy surgery, 3 patients). RESULTS: Twenty-six iMRI examinations were
      performed, 3 immediately before surgical incision, 9 during surgery (operative
      field partially closed), and 14 immediately postsurgery (operative field fully
      closed but patient still anesthetized and draped). Minor technical dysfunctions
      prolonged 10 iMRI procedures; however, no serious iMRI-related incidents
      occurred. Twenty-three iMRI examinations took an average of 78 +/- 20 minutes to
      perform. In three patients, iMRI led to further tumor resection because removable
      residual tumor was identified. Complete tumor resection was achieved in 15 of the
      18 cases. CONCLUSION: The layout of the new complex allows open access to the 3-T
      iMRI system except when it is in use under surgical conditions. Three patients
      benefited from the iMRI examination to achieve total resection. No permanent
      complications were observed. Therefore, the 3-T iMRI is feasible and appears to
      be a safe tool for intraoperative surgical planning and assessment.

PMID- 18812953
TI  - Surgery for convexity meningiomas.
AB  - OBJECTIVE: Meningiomas that occur over the convexity of the brain are the most
      common meningiomas, but little has been published about their contemporary
      management. We aimed to analyze a large series of convexity meningiomas with
      respect to surgical technique, complication rates, and pathological factors
      leading to recurrence. METHODS: We retrospectively reviewed 163 cases of
      convexity meningiomas operated on in our institution by the senior author (PMB)
      between 1986 and 2005. The median follow-up time was 2.3 years (range, 1-13 yr).
      RESULTS: Convexity tumors represented 22% of all meningiomas operated on. There
      was a female:male ratio of 2.7:1. Median age was 57 years (range, 20-89 yr).
      Image-guided surgery was used on all cases in the last 5 years. The 30-day
      mortality rate was 0%. The incidence of new neurological deficits was 1.7%, and
      the overall complication rate was 9.4%. The pathology of the tumors was benign in
      144 (88.3%), atypical in 16 (9.8%), and anaplastic/malignant in 3 (1.8%). In six
      of the cases designated "benign," there were borderline atypical features. The 5
      year recurrence rate for benign meningiomas was 1.8%, atypical meningiomas 27.2%,
      and anaplastic meningiomas 50%. The two cases of benign tumor recurrences
      involved tumors with borderline atypia and high MIB-1 indices. The borderline
      atypical cases had a 5-year recurrence-free survival rate of only 55.9%, more
      closely approximating that of tumors designated "atypical." CONCLUSION: Convexity
      meningiomas can be safely removed using modern image-guided minimally invasive
      surgical techniques with a very low operative mortality. Benign convexity
      meningiomas having a Simpson Grade I complete excision have a very low recurrence
      rate. The recurrence rates of atypical and malignant tumors are significantly
      higher, and borderline atypical tumors should be considered to behave more like
      atypical rather than benign lesions. Longer-term follow-up data are needed to
      more accurately determine the recurrence rates of benign meningiomas.

PMID- 18812954
TI  - Predictors of peritumoral edema after stereotactic radiosurgery of supratentorial
      meningiomas.
AB  - OBJECTIVE: Anecdotal evidence suggests that radiosurgical ablation of
      parasagittal meningiomas may be associated with increased risk of subsequent
      edema. Potential predictors of postradiosurgical peritumoral edema, including
      parasagittal tumor location, tumor size, and treatment dose, were evaluated.
      METHODS: We retrospectively reviewed records of 102 patients with 111
      supratentorial meningiomas treated with CyberKnife (Accuray, Inc., Sunnyvale, CA)
      stereotactic radiosurgery (SRS). A median marginal dose of 18.0 Gy (range, 11.3
      25.0 Gy) was delivered in 1 to 5 sessions (fractions). Potential predictors of
      posttreatment symptomatic edema were evaluated using Fisher's exact test.
      RESULTS: Of the 102 patients followed for a mean of 20.9 months (range, 6-77 mo),
      15 (14.7%) developed symptomatic edema after SRS. Nine of 31 with parasagittal
      meningiomas (29.0%) and 6 of 80 with nonparasagittal supratentorial meningiomas
      (7.5%) developed symptomatic edema (P = 0.0053). Compared with patients with
      meningiomas in nonmidline supratentorial locations, patients with parasagittal
      meningiomas were more than 4 times as likely to develop symptomatic edema after
      SRS (odds ratio, 4.1; 95% confidence interval, 1.5-11.5). The 6-, 12-, and 18
      month actuarial rates of symptomatic edema development were significantly greater
      for patients with parasagittal meningiomas than for patients with nonparasagittal
      meningiomas (17.8 versus 1.3%, 25.4 versus 5.8%, and 35.2 versus 7.8%,
      respectively). CONCLUSION: Patients with parasagittal meningiomas are at greater
      risk of developing peritumoral symptomatic edema after SRS. Close follow-up after
      SRS may be particularly important in such patients. These results highlight the
      need to pursue strategies that could decrease the incidence of postradiosurgical
      edema in patients with parasagittal meningioma.

PMID- 18812955
TI  - The role of stereotactic radiosurgery for intracranial hemangioblastomas.
AB  - OBJECTIVE: To evaluate the role of stereotactic radiosurgery (SRS) in the
      management of recurrent or residual intracranial hemangioblastomas, we assessed
      tumor control, survival, and complications in 32 consecutive patients. METHODS:
      We retrospectively reviewed records of 32 consecutive hemangioblastoma patients
      (74 intracranial tumors) who underwent gamma knife SRS. The median patient age
      was 43.8 years (range, 21.3-79.4 yr). Thirty-one patients had undergone previous
      surgical resections. Nineteen patients had sporadic lesions (22 tumors), and 13
      patients had von Hippel-Lindau disease-associated hemangioblastomas (52 tumors).
      The median SRS target volume was 0.72 mL (range, 0.08-16.6 mL), and the median
      marginal dose was 16.0 Gy (range, 11-20 Gy). RESULTS: At a median of 50.1 months
      (range, 6.0-165.4 mo), seven patients had died from disease progression, and one
      patient had died secondary to heart failure. The overall survival after
      radiosurgery was 100%, 94.4%, and 68.7% at 1, 3, and 7 years, respectively.
      Follow-up imaging studies demonstrated tumor control in 68 tumors (91.9%). The
      progression-free survival after SRS at 1, 3, and 5 years was 96.9%, 95.0%, and
      89.9%, respectively. Factors associated with an improved progression-free
      survival included von Hippel-Lindau disease-associated hemangioblastoma, solid
      tumor, lower tumor volume, and greater marginal dose. CONCLUSION: SRS is an
      important tool in the management of hemangioblastomas and is associated with a
      high tumor control rate and a low risk of adverse radiation effects.

PMID- 18812956
TI  - Diffusion tensor tractography: corticospinal tract fiber reduction is associated
      with temporary hemiparesis in benign extracerebral lesions.
AB  - OBJECTIVE: Benign extracerebral lesions such as meningiomas may cause hemiparesis
      by compression and deviation without infiltrating the white matter. We used
      magnetic resonance diffusion tensor imaging and diffusion tensor tractography to
      investigate the effects of benign extracerebral lesions on the corticospinal
      tract (CST). METHODS: Thirteen patients with extracerebral lesions (11 benign
      meningiomas and 2 benign cysts) underwent magnetic resonance diffusion tensor
      imaging and diffusion tensor tractography of the CST using fiber assignment by
      continuous tractography. The CST was reconstructed and assessed by comparing the
      ipsilateral and unaffected contralateral fibers. The tumor volume, relative
      fractional anisotropy, fiber deviation, relative fiber number, and relative fiber
      per voxel were compared between patients without and with temporary presurgical
      hemiparesis. RESULTS: Seven patients without hemiparesis and five patients with
      temporary hemiparesis were analyzed; one patient had permanent weakness and was
      excluded from analysis. There was no significant difference in the tumor volume,
      relative fractional anisotropy, presence of cerebral edema, or CST deviation
      between groups. In patients with temporary hemiparesis, the median relative fiber
      number (mean, 0.35 +/- 0.32) and relative fiber per voxel (mean, 0.49 +/- 0.14)
      were significantly reduced compared with patients without hemiparesis (0.92 +/-
      0.55, P = 0.04; and 0.96 +/- 0.28, P < 0.01, respectively). CONCLUSION: In
      patients with benign extracerebral lesions, reduction in fiber number and fiber
      per voxel, but not fiber deviation, correlated with temporary hemiparesis.
      Clinical recovery was possible even if the CST fibers detected by diffusion
      tensor tractography were reduced by benign extracerebral lesions.

PMID- 18812957
TI  - Transcerebellar stereotactic biopsy for lesions of the brainstem and peduncles
      under local anesthesia.
AB  - OBJECTIVE: For certain brainstem lesions, a diagnostic biopsy is required for
      treatment planning. We reviewed the indications, safety, and diagnostic
      effectiveness of a transcerebellar stereotactic biopsy using local anesthesia and
      sedation. METHODS: We retrospectively reviewed hospital records for all adult
      patients with symptomatic lesions of the pons and/or cerebellar peduncle who
      underwent an awake transcerebellar stereotactic biopsy at our institution over a
      7-year period. Our technique features several modifications from the standard
      method and was performed under local anesthesia with patients in the semi-sitting
      position. RESULTS: Our rate of diagnostic success (92%) was comparable to those
      in other published reports. However, only 5 (42%) of 12 biopsy-derived diagnoses
      were consistent with those predicted from preoperative magnetic resonance
      imaging. There were no deaths, and the only neurological complication was a
      cranial nerve palsy. Diagnoses in the 13 cases included infiltrative glioma (),
      metastases (), lymphoma (), encephalitis (), and reactive astrogliosis ().
      CONCLUSION: Tissue diagnosis of lesions in the brainstem and cerebellar peduncles
      continues to be a significant challenge, with the potential for major morbidity.
      With appropriate patient selection, however, awake transcerebellar biopsy is a
      safe and effective procedure that can change clinical management and provide
      important prognostic information.

PMID- 18812958
TI  - Delayed visual deficits and monocular blindness after endovascular treatment of
      large and giant paraophthalmic aneurysms.
AB  - OBJECTIVE: Paraophthalmic aneurysms may exert mass effect on the optic apparatus.
      Although surgical clipping and endovascular coiling of these aneurysms can be
      complicated by immediate postoperative visual deterioration, endovascular coil
      embolization has the unique risk of visual complications later (>24 h) in the
      perioperative period. METHODS: Six patients with a delayed onset of vision loss
      after technically successful coil embolization of paraophthalmic region aneurysms
      were identified. All available clinical, angiographic, and cross sectional
      imaging for these patients, in addition to histopathological data, were reviewed.
      RESULTS: Six patients who underwent endovascular treatment of paraclinoid
      aneurysms at our institutions developed delayed postoperative visual decline.
      Four were treated with combination hydrogel-coated and bare platinum coils, one
      with hydrogel-coated coils, and one with bare platinum coils. Three patients
      presented with some degree of visual impairment caused by their aneurysms.
      Catheter angiography performed after the visual decline revealed no etiology in
      any of the cases. Magnetic resonance imaging was performed in all patients and
      was unremarkable in two. At follow-up, two had improved, three remained
      unchanged, and one patient died before any follow-up assessment of her vision.
      CONCLUSION: Both acute and delayed visual disturbances can present after the
      endovascular treatment of carotid artery paraophthalmic aneurysms. Delayed visual
      deterioration can be observed up to 35 days after embolization. Although the
      cause is still undefined, it is likely that the more delayed visual deterioration
      can be attributed to progression of mass effect and/or perianeurysmal
      inflammatory change. Our case series raises the possibility that this phenomenon
      may be more likely with HydroCoil (HydroCoil Embolic System; MicroVention, Aliso
      Viejo, CA). This possibility should be taken into account by
      neurointerventionists when selecting a coil type to treat large paraophthalmic
      aneurysms.

PMID- 18812959
TI  - Results of endovascular treatment of traumatic intracranial aneurysms.
AB  - OBJECTIVE: To present results of early angiographic diagnosis and endovascular
      treatment of traumatic intracranial aneurysms (TICA). METHODS: From June 2002 to
      December 2006, diagnostic angiography was performed on patients with moderate to
      severe traumatic brain injury that involved a cranial base fracture or a
      penetrating brain injury with a tract from the penetrating agent that entered at
      the pterional area, went through the middle cerebral artery candelabra, and
      crossed the midline. TICAs were treated by various endovascular techniques during
      the same angiographic procedure. RESULTS: Thirty-four patients with traumatic
      brain injury underwent angiography (25 penetrating brain injuries, nine blunt
      injuries); 13 TICAs were diagnosed (10 penetrating brain injuries, three blunt
      injuries). The Glasgow Coma Scale score at diagnosis ranged from 5 to 15.
      Angiography was performed for screening in eight patients and for clinical
      indications in five patients; 11 TICAs were diagnosed before rupture. Seven
      aneurysms were located on branches of the middle cerebral artery, two on
      pericallosal branches of the anterior cerebral artery, and four on the internal
      carotid artery. No recanalization was detected in 12 patients. One patient
      treated with a bare stent and coiling had a growing intracavernous
      pseudoaneurysm; therefore, internal carotid artery occlusion with extracranial
      intracranial microvascular bypass was performed. Six patients refused
      angiographic follow-up, but computed tomographic angiography has failed to show
      recanalization. No patient presented with delayed bleeding (mean follow-up, 2.6
      yr). There were no procedure-related complications or mortality. CONCLUSION:
      Early angiographic diagnosis with immediate endovascular treatment provided an
      effective approach for TICA detection and management. Endovascular therapy is
      versatile and offers a valuable alternative to surgery, allowing early aneurysm
      exclusion with excellent results.

PMID- 18812960
TI  - Language reorganization in aphasics: an electrical stimulation mapping
      investigation.
AB  - OBJECTIVE: The purpose of this investigation was to determine whether clinical
      speech deficits after brain injury are associated with functional speech
      reorganization. METHODS: Across an 18-year interval, 11 patients with mild-to
      moderate speech deficits underwent language mapping as part of their treatment
      for intractable epilepsy. These "aphasics" were compared with 14 matched
      "control" patients with normal speech who also were undergoing epilepsy surgery.
      Neuroanatomic data were compared with quantitative language profiles and clinical
      variables. RESULTS: Cortical lesions were evident near speech areas in all
      aphasia cases. As expected, aphasic and control patients were distinguished by
      quantitative language profiles. The groups were further distinguished by the
      anatomic distribution of their speech sites. A significantly greater proportion
      of frontal speech sites was found in patients with previous brain injury,
      consistent with frontal site recruitment. The degree of frontal recruitment
      varied as a function of patient age at the time of initial brain injury; earlier
      injuries were associated with greater recruitment. The overall number of speech
      sites remained the same after injury. Significant associations were found between
      the number of the speech sites, naming fluency, and the lesion proximity in the
      temporal lobe. CONCLUSION: Language maps in aphasics demonstrated evidence for
      age-dependent functional recruitment in the frontal, but not temporal, lobe. The
      proximity of cortical lesions to temporal speech sites predicted the overall
      extent of temporal lobe speech representation and performance on naming fluency.
      These findings have implications for neurosurgical planning in patients with
      preoperative speech deficits.

PMID- 18812961
TI  - Intracranial electroencephalography with subdural grid electrodes: techniques,
      complications, and outcomes.
AB  - OBJECTIVE: Intracranial subdural grid monitoring is a useful diagnostic technique
      for surgical localization in patients with intractable partial epilepsy. The
      rationale for the present study was to assess the morbidity of intracranial
      recordings and the surgical outcomes. METHODS: We retrospectively reviewed the
      clinical data for 189 unique patients undergoing 198 intracranial subdural grid
      monitoring sessions between 1996 and 2004 at a tertiary epilepsy center. RESULTS:
      The mean age of patients undergoing monitoring was 28 +/- 14 years. An average of
      63 +/- 23 electrodes were inserted. The mean duration of monitoring was 8 +/- 4
      days. Localization of an epileptogenic zone occurred in 156 sessions (79%)
      resulting in 136 resections (69%). There were 13 major complications (6.6%),
      including five infections and six hematomas. Three patients (1.5%) developed
      permanent deficits related to implantation. Sixty-two (47%) of 136 patients
      undergoing resection were seizure-free after resection. An additional 38 patients
      (28%) had a significant reduction in seizures. The mean follow-up was 51 +/- 30
      months. The duration of monitoring, bone flap replacement, number of electrodes,
      and perioperative corticosteroids were not associated with infection or
      complication. CONCLUSION: Subdural grid monitoring for identification an
      epileptogenic focus is high yield, revealing a focus in 79% of monitoring
      sessions. Complications rarely result in permanent morbidity (1.5%). Surgical
      outcome indicated that 74% of patients experienced a favorable reduction in
      seizure tendency.

PMID- 18812962
TI  - Visual field defects in selective amygdalohippocampectomy for hippocampal
      sclerosis: the fate of Meyer's loop during the transsylvian approach to the
      temporal horn.
AB  - OBJECTIVE: Meyer's loop, the most vulnerable part of the optic radiations during
      approaches to the temporomedial region, extends to the tip of the temporal horn
      and is often encountered in epilepsy surgery. The risk of damaging Meyer's loop
      during transsylvian selective amygdalohippocampectomy peaks while accessing the
      temporal horn through its roof by opening the inferior limiting sulcus of the
      insula. In this prospective study, we sought to evaluate and identify the
      incidence of visual field deficits in a homogeneous group of patients who had
      temporal lobe epilepsy with hippocampal sclerosis and who underwent transsylvian
      selective amygdalohippocampectomy. METHODS: We studied 30 patients who were
      referred for epilepsy surgery for intractable complex partial and/or secondary
      generalized seizures and evaluated according to a noninvasive protocol. All
      patients underwent selective amygdalohippocampectomy for temporal lobe epilepsy
      with hippocampal sclerosis using the standard transsylvian approach. Visual field
      deficits were examined preoperatively in 30 patients, by either a confrontation
      method (n = 18) or standard Goldmann perimetry (n = 12) and postoperatively in
      all patients using standard Humphrey digital perimetry. RESULTS: Visual field
      examination was normal in all patients before surgery. Humphrey perimetric
      measurement revealed visual field deficits in 11 patients (36.6%) after surgery.
      CONCLUSION: We have shown that there is a considerable risk of having visual
      field deficits after standard transsylvian selective amygdalohippocampectomy
      owing to the interruption of the anterior bundle of the optic radiation fibers,
      which most likely occurs while opening the temporal horn through the inferior
      limiting sulcus of the insula.

PMID- 18812963
TI  - Outcome of extratemporal epilepsy surgery experience of a single center.
AB  - OBJECTIVE: Our aim was to determine the surgical outcome in adult patients with
      intractable extratemporal epilepsy and follow it over time. METHODS: We
      retrospectively studied the operative outcome in 218 consecutive adult patients
      with extratemporal lesions who underwent resective surgical treatment for
      intractable partial epilepsy in the Bethel Epilepsy Center, Bielefeld, Germany,
      between 1991 and 2005. Patients were divided into three groups according to the 5
      year period in which the surgical procedure took place. RESULTS: Group I (1991
      1995) consisted of 64 patients. The postoperative Engel Class I outcome was 50%
      at 6 months, 44.4% at 2 years, and 45.2% at 5 years. Group II (1996-2000)
      included 91 patients. Engel Class I outcome was 57.1% at 6 months, 53.8% at 2
      years, and 53.5% at 5 years. In Group III (2001-2005), there were 63 patients.
      Engel Class I outcome was 65.1% at 6 months, 61.3% at 2 years, and 60.6% at 5
      years. Short duration of epilepsy, surgery before 30 years of age, pathological
      findings of neoplasm, and well-circumscribed lesions on the preoperative magnetic
      resonance imaging scan were good prognostic factors. Poor prognostic factors were
      one or more of the following: psychic aura, generalized tonic-clonic seizure,
      versive seizure, history of previous surgery, and focal cortical dysplasia. On
      multivariate analysis, only the presence of well-circumscribed lesions on
      preoperative magnetic resonance imaging predicted a positive outcome (P = 0.001).
      CONCLUSION: Our results indicate that extratemporal epilepsy surgery at the
      Bethel Epilepsy Center has become more effective in the treatment of
      extratemporal epilepsy patients over the years, ensuring continuous improvement
      in outcome. This improvement can be attributed mainly to more restrictive patient
      selection.

PMID- 18812964
TI  - Neuropsychological effects of shunt treatment in idiopathic normal pressure
      hydrocephalus.
AB  - OBJECTIVE: To prospectively evaluate the effects of shunting on the
      neuropsychological performance of patients with idiopathic normal pressure
      hydrocephalus (INPH), to compare their performance with that of healthy
      individuals, and to estimate the predictive utility of putatively important
      factors. METHODS: A consecutive series of 47 patients with INPH underwent
      neurological, radiological, and neuropsychological examinations before and 3
      months after shunt surgery. The same neuropsychological tests, measuring simple
      and target reaction times, dexterity, memory and learning, working memory, and
      aspects of executive functioning, were also administered to 159 healthy
      individuals. RESULTS: Performance on all neuropsychological tests, except Simple
      Reaction Time and Digit Span, significantly improved after surgery, with more
      severe functional deficits showing greatest improvement. Age, education,
      duration, vascular comorbidity, sex, and onset symptom all failed to predict the
      neuropsychological effects of treatment. Despite improvement 3 months after shunt
      surgery, INPH patients were still outperformed by healthy individuals.
      CONCLUSION: Most of the wide range of neuropsychological functions that are
      affected by INPH are markedly improved by shunt treatment, but not completely
      restored.

PMID- 18812965
TI  - Vertebral body replacement systems with expandable cages in the treatment of
      various spinal pathologies: a prospectively followed case series of 60 patients.
AB  - OBJECTIVE: Vertebral body reconstruction after corpectomy has become a common
      surgical procedure. The authors describe a prospectively followed case series of
      patients treated with expandable cages for various indications. METHODS: Sixty
      patients underwent single or multilevel corpectomy for degenerative stenosis (13
      patients), herniated disc (7 patients), deformity (14 patients), traumatic
      fracture (3 patients), infection (1 patient), or tumor (22 patients). Six
      different expandable vertebral body systems were used in the cervical spine (41
      patients), thoracic spine (15 patients), and lumbar spine (4 patients). All
      patients were evaluated clinically and radiographically. RESULTS: Thirty-nine
      patients underwent single-level corpectomy, 18 patients underwent two-level
      corpectomy, and 3 patients underwent three-level corpectomy. Anterior
      reconstruction alone was performed in 30 patients; circumferential reconstruction
      was performed in 30 patients, 9 of whom underwent reconstruction through a
      posterior approach only. At the time of the final follow-up examination (mean, 9
      mo), the Nurick grade improved significantly. Ninety-five percent of the patients
      maintained or improved their Frankel score and 67% had good clinical results. The
      regional angulation was corrected significantly (4.0 +/- 9.0 degrees, P = 0.002),
      and the segment height increased significantly (3.5 +/- 8.0 mm, P = 0.002). Bony
      fusion was achieved in 93% of the cases. Subsidence was documented in nearly half
      of the patients (1.4 +/- 2.0 mm) and was reduced after circumferential fusion
      (0.9 +/- 1.9 mm, P = 0.08). Eighteen patients (30%) had complications and 12
      patients (20%) underwent revision surgery. CONCLUSION: Expandable vertebral body
      replacement systems can provide solid anterior column constructs with restoration
      of height and sagittal alignment. Favorable clinical outcome was shown in most
      patients, although the complication and reoperation rates are rather high.

PMID- 18812966
TI  - Radiological findings and clinical course of conus lipoma: implications for
      surgical treatment.
AB  - OBJECTIVE: A significant variety in morphology of conus lipomas may underlie
      differences in clinical presentation of the patients and controversy in surgical
      management. We retrospectively studied 58 patients with conus lipomas at our
      institutions. The purpose of this study was to infer the clinical course from the
      radiological findings and to provide information for decision-making in planning
      for surgical treatment. METHODS: The patients underwent untethering surgery
      between 1984 and 2005. There were 35 transitional and 23 dorsal lipomas. The age
      at surgery ranged from 1 month to 50 years (median, 4 yr). Preoperative clinical
      history, radiological findings, and postoperative results were analyzed. RESULTS:
      Fifteen patients were asymptomatic, and 43 patients were symptomatic
      preoperatively. Twenty-one patients presented with motor deficits of the lower
      extremities. In seven patients, motor deficits appeared early, before 1 year of
      age. Massive lipomas compressing the cord or herniation of the spinal cord into
      the subcutaneous tissue were characteristic findings of such early deterioration.
      Motor deficits were present in 73% of patients with lipomas extending to the
      lumbar level, whereas 88% of patients with lipomas confined to the sacral level
      had only urinary deficits. During a mean postoperative follow-up period of 7.9
      years, 4 (27%) of the 15 asymptomatic patients developed urinary and/or motor
      deficits, and 12 (28%) of the 43 symptomatic patients showed further neurological
      deterioration. CONCLUSION: This study demonstrates that the location and
      morphology of conus lipomas influence the neurological presentation of the
      patients. Early prophylactic surgery is a reasonable treatment option if early
      deterioration is predicted by imaging studies.

PMID- 18812967
TI  - Contralateral C7 transfer via the prespinal and retropharyngeal route to repair
      brachial plexus root avulsion: a preliminary report.
AB  - OBJECTIVE: We sought to investigate a shorter and safer route for contralateral
      C7 transfer. METHODS: Eight male patients were treated from December 2005 to
      November 2006. Their ages ranged from 22 to 43 years (average, 30 yr). Five
      patients had total brachial plexus avulsion. The operative delay was from 2 to 6
      months (mean, 4 mo). The bilateral scalenus anterior muscles were transected
      before a prespinal and retropharyngeal tunnel was made. The contralateral C7
      nerve root was used to repair the upper trunk or the infraclavicular lateral cord
      and posterior cord of the injured side via this route, with the use of direct
      neurorrhaphy or nerve grafting. RESULTS: The length of the harvested
      contralateral C7 nerve root was 4.67 +/- 0.52 cm in the first five patients. The
      nerve graft was 6.25 +/- 0.35 cm long for repairing supraclavicular brachial
      plexus and 8.56 +/- 0.45 cm long for repairing infraclavicular brachial plexus.
      The length of the harvested contralateral C7 nerve root averaged 6.85 cm in the
      last three patients, two of whom had direct neurorrhaphy to the C5 and six
      residual nerve roots; in the other patient, a nerve graft 3 cm in length was
      used. Transient contralateral sensory symptoms were reported in most patients. In
      all cases, shoulder abduction and elbow flexion recovered by 12 months
      postoperatively. CONCLUSION: Transection of the bilateral scalenus muscles can
      reduce the length of the nerve graft and allow the C7 nerve to be transferred
      more smoothly and safely through the prespinal and retropharyngeal route; this
      method also favors nerve regeneration and functional recovery.

PMID- 18812968
TI  - CXCR4 expression is elevated in glioblastoma multiforme and correlates with an
      increase in intensity and extent of peritumoral T2-weighted magnetic resonance
      imaging signal abnormalities.
AB  - OBJECTIVE: With the objective of investigating the utility of CXCR4, a chemokine
      receptor known to mediate glioma cell invasiveness, as a molecular marker for
      peritumoral disease extent in high-grade gliomas, we sought to characterize the
      expression profile of CXCR4 in a large panel of tumor samples and determine
      whether CXCR4 expression levels within glioblastoma multiforme might correlate
      with radiological evidence of a more extensive disease process. METHODS: Freshly
      resected tumor tissue samples were processed for immunohistochemical and
      quantitative polymerase chain reaction analyses to identify and quantify
      expression levels of CXCR4 and its corresponding ligand CXCL12. T1 postcontrast
      and T2-weighted magnetic resonance imaging brain scans were used to generate
      voxel signal intensity histograms that were quantitatively analyzed to determine
      the extent and intensity of peritumoral signal abnormality as a marker of
      disseminated disease in the brain. RESULTS: CXCR4 expression was markedly
      elevated in Grade III and IV tumors compared with Grade II gliomas.
      Significantly, when patients with glioblastoma multiforme were segregated into
      two groups based on CXCR4 expression level, we observed a statistically
      significant increase in the intensity and extent of peritumoral magnetic
      resonance imaging signal abnormalities associated with CXCR4 high-expressing
      gliomas. CONCLUSION: Our data confirm that high-grade gliomas robustly express
      CXCR4 and demonstrate a correlative relationship between expression levels of the
      CXCR4 receptor and the magnetic resonance imaging-based finding of a diffuse and
      more extensive disease process in the brain. CXCR4 expression status may,
      therefore, prove useful as a marker of disseminated disease in patients with
      glioblastoma multiforme.

PMID- 18812969
TI  - Krit1 modulates beta 1-integrin-mediated endothelial cell proliferation.
AB  - OBJECTIVE: Using ribonucleic acid interference on cultured cell lines, we
      examined the role of Krev interaction trapped 1 (krit1) and integrin cytoplasmic
      domain-associated protein-1 alpha (icap1alpha) in beta1-integrin-mediated cell
      proliferation. METHODS: Upon depletion of either krit1 or icap1alpha in the HeLa
      cells, umbilical vein endothelial cells, and microvascular endothelial cells, we
      examined the cell number and proliferation changes in the cells, followed by the
      evaluation of beta1-integrin-mediated mitogen-activated protein kinase signal
      pathway and microscopic study. RESULTS: Depletion of krit1 reduces cell number
      and decreases endothelial cell proliferation. Examination of beta1-integrin
      signaling downstream of focal adhesion kinase reveals decreased phosphorylation
      along the extracellular signal-regulated kinase/mitogen-activated protein kinase
      pathway. Depletion of icap1alpha, a protein known to interact with krit1, has
      similar effects, suggesting synergistic function. We also show that krit1
      colocalizes with icap1alpha in both the nucleus and the cytoplasm; however, most
      of icap1alpha is found in the nucleus and most of krit1 is found in the cytoplasm
      at steady state. On depletion of krit1, icap1alpha decreases in the cytoplasm and
      is no longer detected in the nucleus. CONCLUSION: Both krit1 and icap1alpha act
      concordantly to play a critical role in beta1-integrin-mediated cell
      proliferation. Our data further suggest that krit1 both stabilizes and shuttles
      icap1alpha and thus modulates its regulation of beta1-integrin-mediated signal
      transduction.

PMID- 18812970
TI  - The Harvard Neurosurgical Service at the Children's Hospital Boston and Brigham &
      Women's Hospital, 1912-2007.
AB  - The Harvard Neurosurgical Service at Brigham and Women's Hospital and Children's
      Hospital Boston has a distinguished history, beginning in 1912 when Dr. Harvey
      Cushing became surgeon-in-chief at the Peter Bent Brigham Hospital. After Cushing
      left in 1932, the Children's Hospital had a dominant role, with the creation and
      development of pediatric neurosurgery under Franc D. Ingraham, Donald Matson,
      John Shillito, and Keasley Welch. In 1987, the service at Brigham and Women's
      Hospital began to grow with the appointment of Dr. Peter Black as chief. In 2000,
      it became a department. In 2002, the clinical services at the two institutions
      were large enough to separate, with Dr. Black continuing as academic chair of
      both. By 2005, the Brigham and Women's Hospital service had 10 neurosurgeons with
      brain tumor, cerebrovascular, spine, and intensive care unit divisions; the
      Children's service had 5 neurosurgeons under Dr. Michael Scott. There were also
      six full-time scientists in the group. Despite reporting on more than 2500 cases
      a year, the combined service continued to have a strong academic program. This
      was helped by a residency with two required research years, an academic day each
      week, faculty committed to research, strong scientific collaborations, and
      contributions from many visiting neurosurgeons and research fellows. In its first
      94 years, the service has been a strong force in clinical, educational,
      political, and research efforts in neurosurgery.

PMID- 18812971
TI  - Stereotactic neurosurgery in the United Kingdom: the hundred years from Horsley
      to Hariz.
AB  - The history of stereotactic neurosurgery in the United Kingdom of Great Britain
      and Northern Ireland is reviewed. Horsley and Clarke's primate stereotaxy at the
      turn of the 20th century and events surrounding it are described, including
      Mussen's development of a human version of the apparatus. Stereotactic surgery
      after the Second World War is reviewed, with an emphasis on the pioneering work
      of Gillingham, Hitchcock, Knight, and Watkins and the contributions from Bennett,
      Gleave, Hughes, Johnson, McKissock, McCaul, and Dutton after the influences of
      Dott, Cairns, and Jefferson. Forster's introduction of gamma knife radiosurgery
      is summarized, as is the application of computed tomography by Hounsfield and
      Ambrose. Contemporary contributions to the present day from Bartlett, Richardson,
      Miles, Thomas, Gill, Aziz, Hariz, and others are summarized. The current status
      of British stereotactic neurosurgery is discussed.

PMID- 18812972
TI  - Dances with wolves.

PMID- 18812976
TI  - Coming to a head.

PMID- 18812979
TI  - Novel I.V. drug approved.

PMID- 18812980
TI  - Safety concerns for two big anemia drugs.

PMID- 18812981
TI  - Kidneys may be tougher than you thought.

PMID- 18812982
TI  - These drugs don't mix.

PMID- 18812983
TI  - Speak up about patient allergies.

PMID- 18812984
TI  - . . . About sciatica.

PMID- 18812985
TI  - Innovative bundle wipes out catheter-related bloodstream infections.

PMID- 18812986
TI  - Using ultrasound to guide PICC and peripheral cannula insertion.

PMID- 18812987
TI  - Preparing a patient for magnetic resonance imaging.

PMID- 18812989
TI  - Risky recycling.

PMID- 18812990
TI  - Not-so-clear choice.

PMID- 18812991
TI  - No ticket to ride for older adults.

PMID- 18812996
TI  - Using antipsychotic drugs safely in older patients.
AB  - Do you know how to monitor an older adult who's receiving an antipsychotic drug?
      Learn the benefits and the pitfalls so you can keep your older patients safe.

PMID- 18812998
TI  - AHA promotes use of prehospital ECGs.

PMID- 18813000
TI  - Caring for a medical/surgical patient with MS.
AB  - Are you prepared to manage the complexities of caring for a patient with multiple
      sclerosis? Here are the details you'll need, from administering drug therapies to
      managing unique coexisting problems your patient may face.

PMID- 18813002
TI  - Making ethical choices: Weighing obligations and virtues.
AB  - Here's a practical guide to solving difficult ethical dilemmas by considering
      your professional duties and your own qualities of honesty, compassion, and self
      respect.

PMID- 18813003
TI  - What's new, what's different.
AB  - Find out about screening and management changes and how to educate patients in
      self-care.

PMID- 18813004
TI  - Understanding critical limb ischemia.
AB  - Find out how to halt this progression of peripheral arterial disease before it
      jeopardizes life and limb.

PMID- 18813007
TI  - Taking a closer look for skin cancer.

PMID- 18813009
TI  - Weighing your words.

PMID- 18813010
TI  - Creatine kinase: An assay with muscle.

PMID- 18813011
TI  - Catching up with cryptosporidiosis.

PMID- 18813013
TI  - Fall-related trauma.

PMID- 18813015
TI  - Data analysis methods and the reliability of analytic epidemiologic research.
AB  - Publications that compare randomized controlled trial and cohort study results on
      the effects of postmenopausal estrogen-plus-progestin therapy are reviewed. The 2
      types of studies agree in identifying an early elevation in coronary heart
      disease risk, and a later developing elevation in breast cancer risk. Effects
      among women who begin hormone therapy within a few years after the menopause may
      be comparatively more favorable for coronary heart disease and less favorable for
      breast cancer. These analyses illustrate the potential of modern data analysis
      methods to enhance the reliability and interpretation of epidemiologic data.

PMID- 18813016
TI  - The sound and the fury: was it all worth it?
AB  - The initial report of coronary heart disease (CHD) results from the trial of
      menopausal hormone therapy within the Women's Health Initiative precipitated
      substantial surprise and concern in the epidemiology research community over the
      apparent differences between the trial results and those of observational
      studies. What followed was 6 years of discussion and debate, frequently
      acrimonious, along with intense methodologic and substantive research attempting
      to reconcile or explain the apparent differences. The results have been an
      impressive improvement in methods to contrast and combine studies of differing
      designs, dramatic illustrations of some central epidemiologic principles,
      insights into likely mechanisms of CHD, and increasing clarity of the public
      health message about menopausal hormone therapy.

PMID- 18813017
TI  - ITT for observational data: worst of both worlds?
AB  - Hernan et al reanalyzed Nurses' Health Study Data on hormone therapy and heart
      disease, to explore further the apparent discrepancy for those results compared
      with findings from the Women's Health Initiative Trial. Hernan et al concludes
      that differences in time since menopause remains the most plausible explanation
      for the different findings. Part of the analysis employs application of the
      "intention-to treat" principle to analyze the observational data. This commentary
      points out some of the weaknesses inherent in that approach, which combines a
      major limitation of observational studies-lack of randomization-with a common
      limitation of trials, imperfect adherence to the assigned treatment.

PMID- 18813018
TI  - Excess gestational weight gain amplifies risks among obese mothers.
AB  - In this issue of Epidemiology, Chen et al report that obese mothers who gained
      the most weight during pregnancy had elevated risk for infant mortality. Other
      outcomes related to excess maternal weight or weight gain not only cause
      complications around the time of birth but also confer elevated chronic disease
      risk for both mother and child. There is good reason to believe that constraining
      gestational weight gain within an optimal range will minimize adverse outcomes.
      Revised gestational weight gain guidelines are needed, especially for obese
      women.

PMID- 18813019
TI  - Spatial and temporal dynamics of influenza outbreaks.
AB  - BACKGROUND: Annual influenza epidemics occur worldwide, resulting in considerable
      morbidity, mortality, and economic burden. Despite this regular occurrence, few
      studies have systematically examined the regional spatiotemporal patterns of
      influenza outbreaks. METHODS: Weekly incidence data for influenza cases in
      Fukuoka Prefecture (Japan) from 29 August 2005 to 3 June 2007 (n = 113,503) were
      geocoded at sentinel medical institutions (mainly pediatric hospitals and
      clinics). Space-time permutation scan statistics were then used to identify
      weekly temporal and spatial clusters of reported cases of influenza during the
      2006-2007 influenza season. RESULTS: In the early phase of the influenza season,
      clusters were detected in the Fukuoka and Kitakyushu urban areas. The clusters
      then diffused gradually and spread into the rural areas of Fukuoka Prefecture.
      After a period of middle- to large-scale epidemic, the outbreak gradually waned.
      CONCLUSIONS: Based on the permutation model, space-time permutation scan
      statistics can play an important role in detecting influenza outbreaks at an
      early stage and identifying the spatiotemporal patterns of geographic spread.

PMID- 18813021
TI  - Occupational exposure to pesticides during pregnancy and neurobehavioral
      development of infants and toddlers.
AB  - BACKGROUND: Few studies have examined the effects of in utero exposure to
      organophosphate and carbamate pesticides on neurobehavioral development in
      infants and young children. This study considers the potential effects of
      maternal occupation in the cut-flower industry during pregnancy on
      neurobehavioral development in Ecuadorian children. METHODS: Data were collected
      during 2003-2004 for 121 children aged 3-23 months and living in the rural
      highland region of Cayambe, Ecuador. Children were administered the Ages and
      Stages Questionnaire and were given specific developmental tests including
      prehension (reach-and-grasp) and visual skills. Information was gathered on
      maternal health and work characteristics, the home environment, and child health
      status. Growth measurements and a hemoglobin finger-prick blood test were
      obtained. We conducted multiple linear and logistic regression analyses. RESULTS:
      Children whose mothers worked in the flower industry during pregnancy scored
      lower on communication (8% decrease in score, 95% confidence interval [CI]: -16%
      to 0.5%) and fine motor skills (13% decrease, 95% CI: -22% to -5), and had a
      higher odds of having poor visual acuity (odds ratio = 4.7 [CI =1.1-20]),
      compared with children whose mothers did not work in the flower industry during
      pregnancy, after adjusting for potential confounders. CONCLUSIONS: Maternal
      occupation in the cut-flower industry during pregnancy may be associated with
      delayed neurobehavioral development of children aged 3-23 months. Possible
      hazards associated with working in the flower industry during pregnancy include
      pesticide exposure, exhaustion, and job stress.

PMID- 18813022
TI  - Recent heterosexual partnerships and patterns of condom use: a weighted analysis.
AB  - BACKGROUND: In epidemiologic studies of sexual partnerships, characteristics are
      often collected in part through detailed questions concerning recent
      partnerships. These data present challenges for analysis. First, although
      research interest generally lies in all partnerships in a certain time period,
      participants may be asked to provide detailed information only concerning their
      most recent, up to a fixed number. As more recent partnerships may differ from
      others, a simple analysis of these data may lead to bias. Second, the total
      number of partnerships for a study participant may be informative, so the analyst
      must choose between inference for the population of partnerships or for a typical
      partnership from the population of individuals. Third, data may be more fully
      recorded for study participants than their partners, and not all partners may be
      eligible to participate. METHODS: We propose weighting to deal with these
      challenges. Weighting provides a sensitivity analysis for the possible selection
      bias due to incomplete reporting. We analyze heterosexual condom use in Britain,
      using data from the National Survey of Sexual Attitudes and Lifestyles 2000.
      RESULTS: The sensitivity of estimates to possible selection bias is low. We find
      that the choice of population for inference is important for prevalence
      estimates, but has relatively little impact on measures of association. By
      defining within-participant partnership predictors we demonstrate how
      participants vary their condom use. We establish that, at least for male
      participants, shorter partnership duration is linked to a higher probability of
      condom use at last sex but lower probability at first sex. CONCLUSION: We
      recommend a weighted analysis approach to recent partnership data, which can be
      simply implemented in standard survey analysis software. In other surveys the
      sensitivity of estimates to possible selection bias may be substantial and this
      will need to be assessed in each case.

PMID- 18813023
TI  - Ambient air pollution and daily mortality among survivors of myocardial
      infarction.
AB  - BACKGROUND: Certain subgroups in the general population, such as persons with
      existing cardiovascular or respiratory disease, may be more likely to experience
      adverse health effects from air pollution. METHODS: In this European multicenter
      study, 25,006 myocardial infarction (MI) survivors in 5 cities were recruited
      from 1992 to 2002 via registers, and daily mortality was followed for 6 to 12
      years in relation to ambient particulate and gaseous air pollution exposure.
      Daily air pollution levels were obtained from central monitor sites, and particle
      number concentrations were measured in 2001 and estimated retrospectively based
      on measured pollutants and meteorology. City-specific effect estimates from time
      series analyses with Poisson regression were pooled over all 5 cities. RESULTS:
      Particle number concentrations and PM10 averaged over 2 days (lag 0-1) were
      associated with increased total nontrauma mortality for patients of age 35 to 74
      (5.6% [95% confidence interval, 2.8%-8.5%] per 10,000/cm and 5.1% [1.6%-9.3%] per
      10 microg/m, respectively). For longer averaging times (5 and 15 days), carbon
      monoxide and nitrogen dioxide were also associated with mortality. There were no
      clear associations with ozone or sulfur dioxide. CONCLUSION: Exposure to traffic
      related air pollution was associated with daily mortality in MI survivors. Point
      estimates suggest a stronger effect of air pollution in MI survivors than among
      the general population.

PMID- 18813024
TI  - Intraindividual variability in serum micronutrients: effects on reliability of
      estimated parameters.
AB  - BACKGROUND: Although serum measures of micronutrients are more specific than
      questionnaires in quantifying nutritional status, the reliability of serum
      measures depends on between- and within-person variability of circulating
      micronutrient levels. The extent to which multiple samples per person might
      improve reliability is useful information for planning studies and interpreting
      results. METHODS: We analyzed levels of 25 micronutrients in serum samples taken
      from 381 Hawaii women at 4-month intervals. For all subjects and for subjects at
      the low and high end of the micronutrient distributions, we calculated inter- and
      intraindividual variability, reliability coefficients, and the number of
      measurements required to limit attenuation in estimated parameters (ie, to keep
      estimates close to their true values). RESULTS: For 18 of the 25 micronutrients,
      a single measurement provided an estimate within 20% of the true value. For
      regression coefficients, 2 measurements were needed to limit attenuation to no
      more than 20% for nearly half of the micronutrients. To achieve no more than 10%
      attenuation, the number of measurements required ranged from 2 to 10 for
      correlation and from 3 to 20 for regression coefficients. To achieve no more than
      5% attenuation, the corresponding ranges were 3 to 21 for correlation and 6 to 42
      regression coefficients. In general, more measurements were required for adequate
      characterization of subjects with relatively high levels of micronutrients than
      for subjects with lower levels. CONCLUSIONS: Our analysis suggests that 2 or 3
      blood measurements are enough to limit attenuation of regression coefficients
      within 20% of the true value for most carotenoids and tocopherols. For 10%
      attenuation or less, 4 or more micronutrient measurements may be needed.

PMID- 18813025
TI  - Maternal obesity and the risk of infant death in the United States.
AB  - BACKGROUND: Maternal obesity (defined as prepregnancy body mass index [BMI]
      >or=30 kg/m) is associated with increased risk of neonatal death. Its association
      with infant death, postneonatal death, and cause-specific infant death is less
      well-characterized. METHODS: We studied the association between maternal obesity
      and the risk of infant death by using 1988 US National Maternal and Infant Health
      Survey data. A case-control analysis of 4265 infant deaths and 7293 controls was
      conducted using SUDAAN software. Self-reported prepregnancy BMI and weight gain
      were used in the primary analysis, whereas weight variables in medical records
      were used in a subset of 4308 women. RESULTS: Compared with normal weight women
      (prepregnancy BMI = 18.5-24.9 kg/m) who gained 0.30 to 0.44 kg/wk during
      pregnancy, obese women had increased risk of neonatal death and overall infant
      death. For obese women who had weight gain during pregnancy of <0.15, 0.15 to
      0.29, 0.30 to 0.44, and >or=0.45 kg/wk, the adjusted odds ratios of infant death
      were 1.75 (95% confidence interval = 1.28-2.39), 1.42 (1.07-1.89), 1.59 (1.00
      2.51), and 2.87 (1.98-4.16), respectively. Nonobese women with very low weight
      gain during pregnancy also had a higher risk of infant death. The subset with
      weight information from medical records had similar results for recorded
      prepregnancy BMI and weight gain. Maternal obesity was associated with neonatal
      death from pregnancy complications or disorders relating to short gestation and
      unspecified low birth weight. CONCLUSIONS: Maternal obesity is associated with
      increased overall risk of infant death, mainly neonatal death.

PMID- 18813026
TI  - Depression and anxiety symptoms affect change in exercise capacity during cardiac
      rehabilitation.
AB  - BACKGROUND: To study whether symptoms of depression and anxiety would affect
      changes in exercise capacity and body mass index (BMI) during rehabilitation.
      DESIGN: Comprehensive cardiac outpatient rehabilitation intervention program.
      METHODS: We investigated exercise capacity, BMI, and symptoms of depression and
      anxiety before and after cardiac rehabilitation in 114 patients with coronary
      artery disease. The Hospital Anxiety and Depression Scale (HADS) was applied to
      assess symptoms of depression (HADS-D) and anxiety (HADS-A). RESULTS: Exercise
      capacity increased (127+/-47 vs. 144+/-51 watts, P<0.001) and symptoms of
      depression (4.0+/-3.6 vs. 2.7+/-2.7, P<0.001) and anxiety (5.4+/-4.4 vs. 4.1+/
      3.6, P<0.001) decreased with the program, whereas BMI did not change. After
      controlling for covariates, HADS-D (r=-0.19, P=0.47) and HADS-A (r=0.17, P<0.09)
      correlated with change in exercise capacity. Change in HADS-A also correlated
      with that in exercise capacity (r=0.18, P<0.06). Changes in depression and
      anxiety were not significantly related to those in BMI. CONCLUSION: Symptoms of
      depression and anxiety affected change in exercise capacity during cardiac
      rehabilitation. Depressive symptoms may impair improvement in exercise capacity,
      thereby mitigating the cardiovascular benefit achieved by cardiac rehabilitation
      programs.

PMID- 18813027
TI  - Severe hepatotoxicity caused by a methasteron-containing performance-enhancing
      supplement.

PMID- 18813028
TI  - Efficacy of high-dose Lactobacillus rhamnosus GG in controlling acute watery
      diarrhea in Indian children: a randomized controlled trial.
AB  - AIM: To evaluate the effective dose of Lactobacillus rhamnosus GG (LGG) as
      probiotic in acute watery diarrhea (AWD) in Indian children. SETTING: Hospital
      based study. DESIGN: Randomized, controlled, blinded trial. METHODS: All patients
      of AWD admitted over 1 year were included in the study. They were randomized into
      3 groups to receive either only oral rehydration solution (ORS) (group
      A/control), ORS+LGG powder containing 10(10) colony forming units (CFU) (group
      B), or ORS+LGG powder containing 10(12) CFU (group C) twice daily for a minimum
      period of 7 days or until diarrhea stopped along with correction of dehydration.
      None of them received any other drug such as antibiotic or antidiarrheal
      medication. The duration and frequency of diarrhea and vomiting were studied.
      Data were analyzed by SPSS-10 software. RESULTS: The study comprised of 559
      patients, group A/controls (n=185), group B (n=188), and group C (n=186). All the
      groups were similar with respect to age, number of breastfed infants,
      presentation with dehydration, degree of protein energy malnutrition, and
      rotavirus infection. The frequency and duration of diarrhea, requirement for
      intravenous therapy, and hospital stay were significantly lower in both the
      intervention groups compared with the controls. There was no significant
      difference between the 2 intervention groups. No complication was observed from
      the doses of LGG used. CONCLUSIONS: Both the doses of LGG (10(10) and 10(12) CFU)
      were equally effective to decrease the frequency and duration of diarrhea and
      reduction in hospital stay in patients of AWD.

PMID- 18813029
TI  - The water immersion technique is easy to learn for routine use during EGD for
      duodenal villous evaluation: a single-center 2-year experience.
AB  - GOALS: We investigated the learning parameters of the immersion technique for the
      assessment of marked villous atrophy (MVA), during routine
      esophagogastroduodenoscopy (EGD). BACKGROUND: The immersion technique offers a
      proven possibility of enhancing the sensitivity of endoscopy in detecting
      duodenal villous atrophy patterns. STUDY: Nine endoscopists with at least 2 years
      of experience, who had previously been trained to perform the immersion
      technique, searched for duodenal villi during routine EGD. In a 2-year study,
      duodenal villi were evaluated underwater duodenoscopy in 432 patients from whom
      duodenal biopsies had been, for various reasons, obtained. The endoscopic
      findings were compared with the histology. The learning parameters of the water
      immersion technique and the accuracy in detecting subjects with MVA were
      observed. RESULTS: A total of 28 (6.5%) patients with MVA were identified during
      endoscopy by the trained endoscopists. All these patients were diagnosed as being
      celiac patients. The sensitivity, specificity, and accuracy (positive and
      negative predictive values) of the immersion technique in detecting MVA patterns,
      irrespective of the endoscopist who performed the examination, were always 100%.
      CONCLUSIONS: The underwater evaluation of the duodenum can be efficiently and
      regularly performed during routine EGD by endoscopists with 2 years of
      experience, after a specific, brief training period. This procedure is simple,
      feasible, and can accurately detect MVA patterns.

PMID- 18813030
TI  - Emergency care of urban women with sexually transmitted infections: time to
      address deficiencies.
AB  - BACKGROUND: Patient education upon diagnosis of a sexually transmitted infection
      (STI) may effect changes in high-risk sexual behavior. OBJECTIVE: Describe
      emergency department (ED) communication with urban female patients treated for
      STIs. METHODS: : This secondary analysis of data collected during a study of ED
      communication used mixed quantitative and qualitative methods. The medical
      records of female patients ages 18 to 35 presenting to an urban ED for low
      abdominal/pelvic pain, gynecological complaints, and urinary symptoms (n = 134)
      were reviewed for STI testing and treatment proportions. A subsample of 30
      audiotaped interactions with women treated for STIs were coded for provider
      assessment of sexual risks and delivery of STI prevention messages. RESULTS:
      Audiotape analysis found sexual histories were very limited and only 17% of women
      received prevention messages. Provider STI treatment had an estimated overall
      sensitivity of 46% (95% CI, 24.4%-69.0%) and specificity of 66% (95% CI, 61.8%
      70.7%). CONCLUSIONS: Urban female patients treated for an STI in the ED rarely
      received recommended STI prevention messages. The study raises policy issues
      regarding the need for quality indicators in acute STI care. Access to STI
      treatment in other practice settings or by alternative methods need to be
      strongly considered.

PMID- 18813031
TI  - Determining risk markers for gonorrhea and chlamydial infection and reinfection
      among adolescents in public high schools.
AB  - BACKGROUND: In response to high adolescent rates of Chlamydia trachomatis (CT)
      and Neisseria gonorrhoeae (GC), Philadelphia began screening in all public high
      schools in 2003. METHODS: Data from 14,862 students who tested more than once in
      the Philadelphia High School STD Screening Program (PHSSSP) during the 2002-2006
      school years were analyzed for factors associated with CT and GC infection.
      Multivariable Cox proportional hazards models and logistic regression models were
      constructed to identify characteristics associated with measured STD rates. A
      secondary analysis assessed short-term reinfection rates among participants
      retesting within the same school year. RESULTS: In the primary analysis, over
      multiple years, the unadjusted female CT/GC rate was more than double that in
      males (6.0 vs. 2.4 cases per 100 person-years, respectively). Among students with
      a baseline positive, males had a higher rate than females (19.9 vs. 17.7 cases
      per 100 person-years, respectively). Among students with a positive test result,
      13.6% were reinfected within the same school year. Females with named partners
      not treated had a higher reinfection rate than all others (85.5 vs. 40.1-45.2
      cases per 100 person-years, respectively). CONCLUSIONS: Clinicians and screening
      programs that offer STD testing to urban high school students, regardless of
      gender, should encourage those with a prior STD history to test more frequently.
      Clinicians should work with infected patients, especially females, to ensure
      their partners are treated.

PMID- 18813033
TI  - Noncardiac surgery for patients with coronary artery stents: timing is
      everything.

PMID- 18813034
TI  - One hand, two hands, or no hands for maximizing airway maneuvers?

PMID- 18813035
TI  - Other monuments to inhalation anesthesia.

PMID- 18813036
TI  - Time and cardiac risk of surgery after bare-metal stent percutaneous coronary
      intervention.
AB  - BACKGROUND: The duration of time that elective noncardiac surgery (NCS) should be
      delayed after percutaneous coronary intervention (PCI) with bare metal stents
      (BMSs) is unknown. METHODS: This large, single-center, retrospective study
      examined the relation between complication rate in patients with BMSs undergoing
      NCS and the duration of time between PCI and NCS. Primary endpoints included in
      hospital major adverse cardiac events (death, myocardial infarction, stent
      thrombosis, or repeat revascularization with either coronary artery bypass
      grafting or PCI of the target vessel) and bleeding events. The relation between
      the events and the timing of noncardiac surgery after PCI with BMS was assessed
      using univariate analysis and multiple logistic regression. RESULTS: From January
      1, 1990, to January 1, 2005, a total of 899 patients were identified. The
      frequency of major adverse cardiac events was 10.5% when NCS was performed less
      than 30 days after PCI with BMS, 3.8% when NCS was performed between 31 and 90
      days after PCI with BMS, and 2.8% when NCS was performed more than 90 days after
      PCI with BMS. In univariate and multivariate analyses, a shorter time interval
      between PCI with BMS and noncardiac surgery was significantly associated with
      increased incidence of major adverse cardiac events (univariate: P < 0.001; odds
      ratio = 4.0; 95% confidence interval, 2.0-8.3; multivariate: P = 0.006; odds
      ratio = 3.2; 95% confidence interval, 1.5-6.9). Bleeding events were not
      associated with time between PCI with BMS and NCS or with the use of antiplatelet
      therapy in the week before NCS. CONCLUSIONS: The incidence of major adverse
      cardiac events is lowest when NCS is performed at least 90 days after PCI with
      BMS.

PMID- 18813037
TI  - Cardiac risk of noncardiac surgery after percutaneous coronary intervention with
      drug-eluting stents.
AB  - BACKGROUND: The American College of Cardiology released a scientific advisory
      that included a recommendation to delay elective of noncardiac surgery (NCS) for
      1 yr after percutaneous coronary intervention (PCI) with a drug-eluting stent
      (DES). METHODS: This single-center, retrospective study examined the risk for
      complications of NCS performed within 2 yr after DES placement and examined
      whether this risk changed based on the time between procedures. The primary
      endpoint was major adverse cardiac events (MACEs) during the hospitalization for
      NCS. Bleeding events were analyzed as a secondary endpoint. RESULTS: From April
      22, 2003, to December 31, 2006, a total of 520 patients underwent NCS within 2 yr
      after PCI with a DES at Mayo Clinic. The majority, 84%, of the DES placed were
      Cypher stents. The frequency of MACE was not found to be significantly associated
      with the time between PCI and NCS (rate of MACEs 6.4, 5.7, 5.9, and 3.3% at 0-90,
      91-180, 181-365, and 366-730 days after PCI with DES, respectively; P = 0.727 for
      comparison across groups). Characteristics found to be associated with MACEs in
      univariate analysis were advanced age (P = 0.031), emergent NCS (P = 0.006),
      shock at time of PCI (P = 0.035), previous history of myocardial infarction (P =
      0.046), and continuation of a thienopyridine (ticlopidine or clopidogrel) into
      the preoperative period (P = 0.040). The rate of transfusion did not seem to be
      associated with antiplatelet therapy use. CONCLUSIONS: The risk of MACEs with NCS
      after DES placement was not significantly associated with time from stenting to
      surgery, but observed rates of MACEs were lowest after 1 yr.

PMID- 18813038
TI  - Effect of progressive mandibular advancement on pharyngeal airway size in
      anesthetized adults.
AB  - BACKGROUND: General anesthesia in adult humans is associated with narrowing or
      complete closure of the pharyngeal airway. The purpose of this study was to
      determine the effect of progressive mandibular advancement on pharyngeal airway
      size in normal adults during intravenous infusion of propofol for anesthesia.
      METHODS: Magnetic resonance imaging was performed in nine normal adults during
      wakefulness and during propofol anesthesia. A commercially available intraoral
      appliance was used to manually advance the mandible. Images were obtained during
      wakefulness without the appliance and during anesthesia with the participants
      wearing the appliance under three conditions: without mandibular advancement,
      advancement to 50% maximum voluntary advancement, and maximum advancement. Using
      computer software, airway area and maximum anteroposterior and lateral airway
      diameters were measured on the axial images at the level of the soft palate,
      uvula, tip of the epiglottis, and base of the epiglottis. RESULTS: Airway area
      across all four airway levels decreased during anesthesia without mandibular
      advancement compared with airway area during wakefulness (P < 0.007). Across all
      levels, airway area at 50% advancement during anesthesia was less than that at
      centric occlusion during wakefulness (P = 0.06), but airway area with maximum
      advancement during anesthesia was similar to that during wakefulness (P = 0.64).
      In general, anteroposterior and lateral airway diameters during anesthesia
      without mandibular advancement were decreased compared with wakefulness and were
      restored to their wakefulness values with 50% and/or maximal advancement.
      CONCLUSIONS: Maximum mandibular advancement during propofol anesthesia is
      required to restore the pharyngeal airway to its size during wakefulness in
      normal adults.

PMID- 18813039
TI  - Coadministration of propofol and remifentanil for lumbar puncture in children:
      dose-response and an evaluation of two dose combinations.
AB  - BACKGROUND: The combination of propofol and remifentanil may be particularly
      suitable for short-duration procedures such as lumbar puncture. The authors
      undertook a two-part study to evaluate coadministration of propofol and
      remifentanil as an anesthetic technique for lumbar puncture in children. METHODS:
      The first part was a sequential allocation dose-finding study to determine the
      minimum effective dose of remifentanil when coadministered with 2.0 or 4.0 mg/kg
      propofol. The second was a randomized double-blind study to compare the
      intraoperative and recovery characteristics of 2.0 or 4.0 mg/kg propofol
      coadministered with the corresponding effective dose of remifentanil. RESULTS:
      Effective doses of remifentanil in 98% of children were 1.50 +/- 1.00 and 0.52 +/
      1.06 microg/kg when coadministered with 2.0 and 4.0 mg/kg propofol,
      respectively. The duration of apnea was longer (median, 110 vs. 73 s; P < 0.05)
      and the time to awakening was shorter (median, 10 vs. 23 min; P < 0.05) after 2.0
      mg/kg propofol plus 1.5 microg/kg remifentanil compared with 4.0 mg/kg propofol
      plus 0.5 microg/kg remifentanil. No child experienced hypotension or
      postprocedure nausea or vomiting after either dose combination. CONCLUSIONS: Both
      dose combinations (2.0 mg/kg propofol plus 1.5 microg/kg remifentanil and 4.0
      mg/kg propofol plus 0.5 microg/kg remifentanil) provide effective anesthesia for
      lumbar puncture in children. However, the intraoperative and recovery
      characteristics of the two dose combinations differ in that the duration of apnea
      increases whereas recovery time decreases as the dose of remifentanil is
      increased and that of propofol is decreased.

PMID- 18813040
TI  - Detecting awareness in children by using an auditory intervention.
AB  - BACKGROUND: The incidence of awareness has been reported to be higher in children
      than in adults. Accurately assessing awareness in children is difficult, and the
      lack of a specific measure of awareness makes it difficult to determine exactly
      how many and why children are aware. The aim of this study was to determine the
      incidence and timing of awareness in children by using auditory stimuli applied
      during anesthesia. METHODS: Three easily identified animal noises were played
      repeatedly through headphones during three specific phases of anesthesia in 539
      children aged 5-12 yr. Children were not told that this would happen. Awareness
      was determined with a structured interview on days 1 and 3 after the anesthetic.
      All positive responses were sent to four adjudicators for assessment, and
      awareness was defined as having occurred if all adjudicators agreed that the
      child was aware. RESULTS: Five hundred children were interviewed at least once
      after the anesthetic. Thirty-five reports were sent to the adjudicators, and one
      child was classified as aware. This child was deemed to be aware even though he
      did not report hearing an animal. CONCLUSIONS: The incidence of awareness in this
      study is less than reported previously.

PMID- 18813041
TI  - Muscle biopsy and in vitro contracture test in subjects with idiopathic
      HyperCKemia.
AB  - BACKGROUND: Persistent high creatine kinase (CK) levels may reflect underlying
      subclinical myopathies. In most cases, pathogenesis is unknown and clinical
      management is unclear. Though clinically asymptomatic, these subjects are
      potentially susceptible to malignant hyperthermia. METHODS: The authors analyzed
      37 subjects with persistent elevation of CK without significant weakness or other
      neurologic symptoms. Neurologic examination was performed according to manual
      muscle testing. Muscle biopsy and the in vitro contracture test were performed in
      all subjects. RESULTS: Twenty-three subjects (51.1%) were completely
      asymptomatic. The others had minor symptoms such as occasional cramps (11
      subjects, 24.4%), fatigue (5 subjects, 11.1%), a combination of cramps and
      fatigue (5 subjects, 11.1%), and muscle pain (1 case, 2.2%). Muscle biopsy
      enabled precise diagnosis in 3 cases and was normal in 3 cases. The more frequent
      changes were variation in fiber size (31.1%), a combination of nuclear
      internalization and variation in fiber size (26.6%), nuclear internalization
      (6.6%), minor mitochondrial changes (4.4%), and neurogenic atrophy (4.4%).
      Immunocytochemical analysis was normal in all patients. In vitro contracture
      testing detected one malignant hyperthermia-susceptible and one malignant
      hyperthermia-equivocal subject. CONCLUSIONS: The evidence of malignant
      hyperthermia susceptibility by in vitro contracture test seems to be relatively
      infrequent among subjects with idiopathic hyperCKemia, but the incidence of true
      malignant hyperthermia in idiopathic hyperCKemia is unknown. Muscle biopsy should
      be considered a useful, though not very sensitive, diagnostic tool in idiopathic
      hyperCKemia, because it enables potentially treatable disorders, such as
      inflammatory myopathies, to be discovered. No uniform morphologic finding typical
      of idiopathic hyperCKemia or malignant hyperthermia susceptibility was identified
      by muscle biopsy.

PMID- 18813042
TI  - Sleep disturbances after posterior scoliosis surgery with an intraoperative wake
      up test using remifentanil.
AB  - BACKGROUND: The intraoperative wake-up test is a standard procedure for early
      recognition of neurologic complications after posterior correction of idiopathic
      scoliosis. In this prospective, single-blinded cohort study, the impact of the
      wake-up test and the opioid used for anesthesia on the quality of the patients'
      sleep after scoliosis surgery was investigated up to 12 months postoperatively.
      METHODS: Patients were classified into three groups: posterior instrumentation
      with wake-up test using remifentanil, anterior instrumentation without wake-up
      test using sufentanil, and posterior instrumentation with wake-up test using
      sufentanil. The quality of sleep was assessed using the Pittsburgh Sleep Quality
      Index questionnaire preoperatively as well as 3, 6, and 12 months
      postoperatively. In addition, data were collected on patients' age, weight, and
      sex, as well as the duration of the operation and anesthesia, amount of blood
      loss, specific opioid dosages, and wake-up test times. Statistical analysis was
      conducted using the Mann-Whitney, Kruskal-Wallis, and Wilcoxon tests. RESULTS:
      There were no differences between groups with regard to baseline characteristics.
      No explicit recall was assessed through all groups. At 3 and 6 months
      postoperatively, the sleep quality in the posterior-remifentanil group was
      significantly poorer than preoperatively and compared with the anterior- and
      posterior-sufentanil groups. No significant differences in wake-up test times
      between groups undergoing posterior instrumentation occurred. CONCLUSIONS: This
      study suggests that patients undergoing scoliosis surgery with an intraoperative
      wake-up test using remifentanil had impaired sleep quality that lasted up to 6
      months postoperatively. No deterioration in sleep quality was observed with
      sufentanil. Large randomized trials are now needed to confirm these preliminary
      results.

PMID- 18813043
TI  - Dexmedetomidine weakens dynamic cerebral autoregulation as assessed by transfer
      function analysis and the thigh cuff method.
AB  - BACKGROUND: Dexmedetomidine, which is often used in intensive care units in
      patients with compromised circulation, might induce further severe decreases in
      cerebral blood flow (CBF) with temporal decreases in arterial pressure induced by
      various stimuli if dynamic cerebral autoregulation is not improved. Therefore,
      the authors hypothesized that dexmedetomidine strengthens dynamic cerebral
      autoregulation. METHODS: Fourteen healthy male subjects received placebo, low
      dose dexmedetomidine (loading, 3 microg x kg(-1) x h(-1) for 10 min; maintenance,
      0.2 microg x kg(-1) x h(-1) for 60 min), and high-dose dexmedetomidine (loading,
      6 microg x kg(-1) x h(-1) for 10 min; maintenance, 0.4 microg x kg(-1) x h(-1)
      for 60 min) infusions in a randomized, double-blind, crossover study. After 70
      min of drug administration, dynamic cerebral autoregulation was estimated by
      transfer function analysis between arterial pressure variability and CBF velocity
      variability, and the thigh cuff method. RESULTS: Compared with placebo, steady
      state CBF velocity and mean blood pressure significantly decreased during
      administration of dexmedetomidine. Transfer function gain in the very-low
      frequency range increased and phase in the low-frequency range decreased
      significantly, suggesting alterations in dynamic cerebral autoregulation in lower
      frequency ranges. Moreover, the dynamic rate of regulation and percentage
      restoration in CBF velocity significantly decreased when a temporal decrease in
      arterial pressure was induced by thigh cuff release. CONCLUSION: Contrary to the
      authors' hypothesis, the current results of two experimental analyses suggest
      together that dexmedetomidine weakens dynamic cerebral autoregulation and delays
      restoration in CBF velocity during conditions of decreased steady state CBF
      velocity. Therefore, dexmedetomidine may lead to further sustained reductions in
      CBF during temporal decreases in arterial pressure.

PMID- 18813044
TI  - Fluoropolymer-based emulsions for the intravenous delivery of sevoflurane.
AB  - BACKGROUND: The intravenous delivery of halogenated volatile anesthetics has been
      previously achieved using phospholipid-stabilized emulsions, e.g., Intralipid.
      However, fluorinated volatile anesthetics, such as sevoflurane, are partially
      fluorophilic and do not mix well with classic nonfluorinated lipids. This effect
      limits the maximum amount of sevoflurane that can be stably emulsified in
      Intralipid to 3.5% vol/vol. This is a significant limitation to the potential
      clinical use of Intralipid-based emulsions. METHODS: The authors prepared a 20%
      vol/vol sevoflurane emulsion using a novel fluorinated surfactant and tested its
      effectiveness and therapeutic index by administering it to male Sprague-Dawley
      rats via intravenous injection into the jugular vein. The median effective dose
      to induce anesthesia (ED50), the median lethal dose (LD50), and the therapeutic
      index (LD50/ED50) were determined. Anesthesia was measured by loss of the forepaw
      righting reflex. RESULTS: The ED50 and LD50 values were found to be 0.41 and 1.05
      ml emulsion/kg body weight, respectively. These lead to a therapeutic index of
      2.6, which compares favorably with previously determined values of emulsified
      isoflurane, as well as values for propofol and thiopental. CONCLUSIONS: A novel
      semifluorinated surfactant was able to considerably increase the maximum amount
      of stably emulsified sevoflurane compared with Intralipid. These formulations can
      be used to rapidly induce anesthesia with bolus dosing from which recovery is
      smooth and rapid.

PMID- 18813045
TI  - Effect of nitrous oxide anesthesia on plasma homocysteine and endothelial
      function.
AB  - BACKGROUND: Endothelial function is impaired with hyperhomocysteinemia. Plasma
      homocysteine is increased by nitrous oxide anesthesia. The current study was
      designed to determine whether endothelial function is impaired after surgery and
      whether this is made worse by exposure to nitrous oxide. METHODS: The authors
      studied 59 patients with cardiovascular disease undergoing noncardiac surgery.
      Patients were randomly allocated to nitrous oxide-based anesthesia (n = 25) or
      nitrous oxide-free anesthesia (control, n = 34). Endothelial function was
      measured by flow-mediated dilation of the brachial artery before and 24 h after
      surgery. In addition, blood was drawn at both time points for the measurements of
      plasma homocysteine, folate, L-arginine, L-citrulline, asymmetric
      dimethylarginine, and nitrate concentrations. RESULTS: The median duration of
      general anesthesia was 4.5 h. Patients had significantly lower flow-mediated
      dilation after surgery (5.1 +/- 3.3 to 3.0 +/- 4.1%; P = 0.001). Duration of
      anesthesia affected endothelial function. In the nitrous oxide group, there was
      an inverse correlation with flow-mediated dilation (r = -0.60, P = 0.004), but in
      the control group, there was a positive correlation (r = 0.61, P < 0.001). When
      compared with control, nitrous oxide exposure was associated with a significant
      increase in postoperative homocysteine (mean difference, 4.9 microm; 95%
      confidence interval, 2.8-7.0 microm; P < 0.0005) and decrease in flow-mediated
      dilation (3.2%; 95% confidence interval, 0.1-5.3%; P = 0.001). Nitrous oxide
      exposure was not associated with change in nitric oxide substrates. CONCLUSIONS:
      Nitrous oxide-based anesthesia increased plasma homocysteine and significantly
      impaired endothelial function in patients undergoing noncardiac surgery. Nitrous
      oxide-based anesthesia could be a risk factor for postoperative cardiovascular
      morbidity.

PMID- 18813046
TI  - Population pharmacokinetic-pharmacodynamic modeling of epidural anesthesia.
AB  - BACKGROUND: In previous studies, the authors reported on the absorption and
      disposition kinetics of levobupivacaine and ropivacaine. The current study was
      designed to develop a population pharmacokinetic-pharmacodynamic model capable of
      linking the kinetic data to the analgesic effects of these local anesthetics
      (i.e., sensory neural blockade). METHODS: A disposition compartmental model was
      fitted to concentration data of the intravenously administered deuterium-labeled
      anesthetics, and a model consisting of two parallel absorption compartments and
      the identified disposition compartments was fitted to concentration data of the
      concomitantly epidurally administered unlabeled anesthetics. The epidural
      segments were modeled by individual central and peripheral absorption
      compartments and effect sites, which were fitted to the simultaneously acquired
      pinprick data. A covariate model incorporated the effects of age. RESULTS: The
      threshold for epidural anesthesia increased from the lower to the higher
      segments. The central effect compartment equilibration half-lives were
      approximately 15 min for levobupivacaine and 25 min for ropivacaine. For
      levobupivacaine, age reduced the equilibration half-lives at all segments; for
      ropivacaine, age increased the anesthetic sensitivity at segments T12 and higher.
      CONCLUSIONS: A population pharmacokinetic-pharmacodynamic model was developed
      that quantitatively described sensory blockade during epidural anesthesia,
      including the effects of age. The model may be useful to individualize dose
      requirements, to predict the time course of sensory blockade, and to study new
      local anesthetics.

PMID- 18813048
TI  - Lumbar plexus block using high-pressure injection leads to contralateral and
      epidural spread.
AB  - BACKGROUND: The main advantage of lumbar plexus block over neuraxial anesthesia
      is unilateral blockade; however, the relatively common occurrence of bilateral
      spread (up to 27%) makes this advantage unpredictable. The authors hypothesized
      that high injection pressures during lumbar plexus block carry a higher risk of
      bilateral or neuraxial anesthesia. METHODS: Eighty patients undergoing knee
      arthroscopy (age 18-65 yr; American Society of Anesthesiologists physical status
      I or II) during a standard, nerve stimulator-guided lumbar plexus block using 35
      ml mepivacaine, 1.5%, were scheduled to be studied. Patients were randomly
      assigned to receive either a low-pressure (< 15 psi) or a high-pressure (> 20
      psi) injection, as assessed by an inline injection pressure monitor (BSmart;
      Concert Medical LLC, Norwell, MA). The block success rate and the presence of
      bilateral sensory and/or motor blockade were assessed. RESULTS: An interim
      analysis was performed at n = 20 after an unexpectedly high number of patients
      had neuraxial spread, necessitating early termination of the study. Five of 10
      patients (50%) in the high-pressure group had a neuraxial block with a dermatomal
      sensory level T10 or higher. In contrast, no patient in the low-pressure group (n
      = 10) had evidence of neuraxial spread. Moreover, 6 patients (60%) in the high
      pressure group demonstrated bilateral sensory blockade in the femoral
      distribution, whereas no patient in the low-pressure group had evidence of a
      bilateral femoral block. CONCLUSIONS: Injection of local anesthetic with high
      injection pressure (> 20 psi) during lumbar plexus block commonly results in
      unwanted bilateral blockade and is associated with high risk of neuraxial
      blockade.

PMID- 18813047
TI  - Brief periods of nitric oxide inhalation protect against myocardial ischemia
      reperfusion injury.
AB  - BACKGROUND: Prolonged breathing of nitric oxide reduces myocardial ischemia
      reperfusion injury, but the precise mechanisms responsible for the
      cardioprotective effects of inhaled nitric oxide are incompletely understood.
      METHODS: The authors investigated the fate of inhaled nitric oxide (80 parts per
      million) in mice and quantified the formation of nitric oxide metabolites in
      blood and tissues. The authors tested whether the accumulation of nitric oxide
      metabolites correlated with the ability of inhaled nitric oxide to protect
      against cardiac ischemia-reperfusion injury. RESULTS: Mice absorbed nitric oxide
      in a nearly linear fashion (0.19 +/- 0.02 micromol/g x h). Breathing nitric oxide
      rapidly increased a broad spectrum of nitric oxide metabolites. Levels of
      erythrocytic S-nitrosothiols, N-nitrosamines, and nitrosyl-hemes increased
      dramatically within 30 s of commencing nitric oxide inhalation. Marked increases
      of lung S-nitrosothiol and liver N-nitrosamine levels were measured, as well as
      elevated cardiac and brain nitric oxide metabolite levels. Breathing low oxygen
      concentrations potentiated the ability of inhaled nitric oxide to increase
      cardiac nitric oxide metabolite levels. Concentrations of each nitric oxide
      metabolite, except nitrate, rapidly reached a plateau and were similar after 5
      and 60 min. In a murine cardiac ischemia-reperfusion injury model, breathing
      nitric oxide for either 5 or 60 min before reperfusion decreased myocardial
      infarction size as a fraction of myocardial area at risk by 31% or 32%,
      respectively. CONCLUSIONS: Breathing nitric oxide leads to the rapid accumulation
      of a variety of nitric oxide metabolites in blood and tissues, contributing to
      the ability of brief periods of nitric oxide inhalation to provide
      cardioprotection against ischemia-reperfusion injury. The nitric oxide metabolite
      concentrations achieved in a target tissue may be more important than the
      absolute amounts of nitric oxide absorbed.

PMID- 18813049
TI  - Differential effect of morphine and morphine-6-glucuronide on the control of
      breathing in the anesthetized cat.
AB  - BACKGROUND: Morphine's metabolite, morphine-6-glucuronide (M6G), activates the mu
      opioid receptor. Previous data suggest that M6G activates a unique M6G receptor
      that is selectively antagonized by 3-methoxynaltrexome (3mNTX). The authors
      compared the effects of M6G and morphine on breathing in the anesthetized cat and
      assessed whether 3mNTX reversal was selective for M6G. METHODS: Step changes in
      end-tidal carbon dioxide concentration were applied in cats anesthetized with
      alpha-chloralose-urethane. In study 1, the effect of the 0.15 mg/kg morphine
      followed by 0.2 mg/kg 3mNTX and next 0.8 mg/kg M6G was assessed in six cats. In
      study 2, the effect of 0.8 mg/kg M6G followed by 0.2 mg/kg 3mNTX and 0.15 mg/kg
      morphine was tested in another six cats. The ventilatory carbon dioxide responses
      were analyzed with a two-compartment model of the ventilatory controller, which
      consists of a fast peripheral and a slow central component. RESULTS: Both opioids
      shifted the ventilatory carbon dioxide responses to higher end-tidal carbon
      dioxide levels. Morphine had a preferential depressant effect within the central
      chemoreflex loop. In contrast, M6G had a preferential depressant effect within
      the peripheral chemoreflex loop. Irrespective of the opioid, 3mNTX caused full
      reversal of and prevented respiratory depression. CONCLUSIONS: In anesthetized
      cats, the mu-opioids morphine and M6G induce respiratory depression at different
      sites within the ventilatory control system. Because 3mNTX caused full reversal
      of the respiratory depressant effects of both opioids, it is unlikely that a
      3mNTX-sensitive unique M6G receptor is the cause of the differential respiratory
      behavior of morphine and M6G.

PMID- 18813050
TI  - Comparison of the immediate effects of surgical incision on dorsal horn neuronal
      receptive field size and responses during postnatal development.
AB  - BACKGROUND: Pain behavior in response to skin incision is developmentally
      regulated, but little is known about the underlying neuronal mechanisms. The
      authors hypothesize that the spatial activation and intensity of dorsal horn
      neuron responses to skin incision differ in immature and adult spinal cord.
      METHODS: Single wide-dynamic-range dorsal horn cell spike activity was recorded
      for a minimum of 2 h from anesthetized rat pups aged 7 and 28 days. Cutaneous
      pinch and brush receptive fields were mapped and von Frey hair thresholds were
      determined on the plantar hind paw before and 1 h after a skin incision was made.
      RESULTS: Baseline receptive field areas for brush and pinch were larger and von
      Frey thresholds lower in the younger animals. One hour after the incision, brush
      and pinch receptive field area, spontaneous firing, and evoked spike activity had
      significantly increased in the 7-day-old animals but not in the 28-day-old
      animals. Von Frey hair thresholds decreased at both ages. CONCLUSIONS: Continuous
      recording from single dorsal horn cells both before and after injury shows that
      sensitization of receptive fields and of background and afferent-evoked spike
      activity at 1 h is greater in younger animals. This difference is not reflected
      in von Frey mechanical thresholds. These results highlight the importance of
      studying the effects of injury on sensory neuron physiology. Injury in young
      animals induces a marked and rapid increase in afferent-evoked activity in second
      order sensory neurons, which may be important when considering long-term effects
      and analgesic interventions.

PMID- 18813051
TI  - Biologic effects of nitrous oxide: a mechanistic and toxicologic review.
AB  - Nitrous oxide is the longest serving member of the anesthesiologist's
      pharmacologic armamentarium but remains a source of controversy because of fears
      over its adverse effects. Recently, the Evaluation of Nitrous oxide In a Gas
      Mixture for Anaesthesia (ENIGMA) trial reported that nitrous oxide use increases
      postoperative complications; further preclinical reports have suggested that
      nitrous oxide may contribute to neurocognitive dysfunction in the young and
      elderly. Therefore, nitrous oxide's longevity in anesthetic practice is under
      threat. In this article, the authors discuss the evidence for the putative
      toxicity of nitrous oxide, from either patient or occupational exposure, within
      the context of the mechanism of nitrous oxide's action. Although it would seem
      prudent to avoid nitrous oxide in certain vulnerable populations, current
      evidence in support of a more widespread prescription from clinical practice is
      unconvincing.

PMID- 18813052
TI  - A rational approach to perioperative fluid management.
AB  - Replacement of assumed preoperative deficits, in addition to generous
      substitution of an unsubstantiated increased insensible perspiration and third
      space loss, plays an important role in current perioperative fluid regimens. The
      consequence is a positive fluid balance and weight gain of up to 10 kg, which may
      be related to severe complications. Because the intravascular blood volume
      remains unchanged and insensible perspiration is negligible, the fluid must
      accumulate inside the body. This concept brings into question common liberal
      infusion regimens. Blood volume after fasting is normal, and a fluid-consuming
      third space has never been reliably shown. Crystalloids physiologically load the
      interstitial space, whereas colloidal volume loading deteriorates a vital part of
      the vascular barrier. The endothelial glycocalyx plays a key role and is
      destroyed not only by ischemia and surgery, but also by acute hypervolemia.
      Therefore, undifferentiated fluid handling may increase the shift toward the
      interstitial space. Using the right kind of fluid in appropriate amounts at the
      right time might improve patient outcome.

PMID- 18813053
TI  - Diagnosis and treatment of glossopharyngeal and vagal neuropathies in a patient
      with laryngopharyngeal reflux.

PMID- 18813054
TI  - Our European study on blood transfusions: three quarters full or one quarter
      empty?

PMID- 18813055
TI  - Propensity analysis: a tool to complement randomized studies.

PMID- 18813056
TI  - The name of the game: no transfusion (or nontransfusion) by cookbook.

PMID- 18813057
TI  - Propensity scores do not necessarily lie!

PMID- 18813059
TI  - Ultrasound-guided regional anesthesia: why can't we all just stay away from the
      nerve?

PMID- 18813060
TI  - When is a single-injection nerve block not really a single injection?

PMID- 18813061
TI  - Can ultrasound impact the risk-benefit ratio for nerve blocks?

PMID- 18813062
TI  - Severe brachial plexopathy after an ultrasound-guided single-injection nerve
      block for total shoulder arthroplasty in a patient with multiple sclerosis: what
      is the likely cause of this complication?

PMID- 18813063
TI  - To be or not to be.

PMID- 18813064
TI  - Nerve blocks, ultrasounds, and multiple sclerosis.

PMID- 18813065
TI  - In ultrasound-guided interscalene block, do we know where the epineurium is?

PMID- 18813069
TI  - Sensitivity change in cornea and tear layer due to incision difference on
      cataract surgery with either manual small-incision cataract surgery or
      phacoemulsification.
AB  - PURPOSE: To describe corneal sensitivity changes caused by different incision
      methods-manual small-incision cataract surgery (manual SICS) and
      phacoemulsification-and their influence on tear film quantity and quality.
      METHODS: This was a prospective observational study conducted in 30 subjects
      undergoing manual SICS or phacoemulsification. Corneal sensitivity was assessed
      before and 1, 7, and 15 days after surgery by Cochet-Bonnet esthesiometer. Tear
      meniscus, noninvasive breakup time, lipid pattern, and Schirmer test results were
      evaluated. Patient symptoms were reviewed based on the Ocular Surface Disease
      Index. RESULTS: In the group undergoing phacoemulsification, corneal sensitivity
      decreased at the incision site and at other sites on days 1, 7, and 15 after
      surgery, whereas in the group undergoing manual SICS, no change in corneal
      sensitivity was noted. Between-group difference in corneal sensitivity was
      significant on days 1, 7, and 15. Aqueous production significantly (P = 0.016)
      increased on the first day in both groups and returned to presurgery level on day
      15. Tear film quality decreased on day 1 only in the group undergoing manual SICS
      (P = 0.035). Tear meniscus and tear lipid profile showed no change in either
      group. Patient symptoms significantly increased on day 1 in both groups, and the
      difference between the 2 groups was significant on day 15 (P = 0.044).
      CONCLUSIONS: Compared with manual SICS, temporal-side incision in
      phacoemulsification decreased corneal sensitivity in the incision site and other
      sites until day 15 and changes in tear film quantity and patient symptoms only on
      day 1.

PMID- 18813070
TI  - A novel technique for performing full-bed deep lamellar keratoplasty.
AB  - In recent years, deep lamellar keratoplasty (DLKP) has become an alternative
      surgical approach successfully applied to the treatment of opaque cornea with
      normal endothelial function. However, techniques for performing DLKP are not
      standardized and have not been perfected compared with penetrating keratoplasty.
      We developed a technique of stromal hooking and viscoelastic detaching to create
      a full-bed exposure of Descemet membrane (DM) for DLKP grafting. The surgical
      procedures include trephining the recipient stroma, exposure of DM by stromal
      hooking process using a forceps tooth as hook, detaching stroma from DM by
      injecting viscoelastic between the 2 layers, removing whole stroma around the
      trephined margin to obtain full-bed exposure of DM, and grafting cryopreserved
      donor button. Unlike previously reported techniques, our technique does not
      attempt directly to dissect stroma but to detach the stromal layer from DM by
      injecting viscoelastic. Using this technique, among 172 eyes we achieved full-bed
      DLKP in 1 attempt of the procedure in 42 (24.4%) eyes, in 2 attempts in 65
      (37.8%) eyes, and in 3 attempts in 45 (26.2%) eyes. Eighteen of 172 (10.5%) eyes
      had microperforation of DM, but DLKP surgery was nonetheless completed. Two
      (1.2%) eyes needed conversion to penetrating keratoplasty because of large
      perforation of DM. We present a detailed illustration of our surgical procedures
      for performing full-bed DLKP in the hope that it may be of help to
      ophthalmologists.

PMID- 18813071
TI  - Autologous serum eye drops for the treatment of dry eye diseases.
AB  - Conventional treatment of dry eye mainly consists of the use of preservative-free
      artificial eye drops and punctal occlusion. None of the commercially available
      artificial tear preparations include essential tear components such as epidermal
      growth factor, hepatocyte growth factor, fibronectin, neurotrophic growth factor,
      and vitamin A-all of which have been shown to play important roles in the
      maintenance of a healthy ocular surface epithelial milieu. We reported previously
      that autologous serum (AS) eye drops contain these essential factors and that AS
      eye drops are beneficial in the treatment of ocular surface diseases such as
      persistent epithelial defects, superior limbic keratoconjunctivitis,
      keratoconjunctivitis sicca, and neurotrophic keratopathy. However, there is some
      controversy regarding the efficacy of AS treatment. We demonstrated that this
      modality is more effective than artificial tears in a randomized control study.
      In in vivo and in vitro experiments, AS eye drops showed marked suppression of
      apoptosis in the conjunctival and corneal epithelium. Albumin, the major protein
      in serum, improved ocular surface damage in vivo and rescued apoptosis after
      serum deprivation in vitro. The biological background of AS eye drops and
      previous clinical studies of these medications for the treatment of dry eye are
      discussed.

PMID- 18813072
TI  - The role of Ca2+ signaling in cell function with special reference to exocrine
      secretion.
AB  - Inositol 1,4,5-trisphosphate (IP3) is a second messenger that induces the release
      of calcium from the endoplasmic reticulum (ER). The IP3 receptor was discovered
      as a developmentally regulated glycophosphoprotein, P400, that is absent in
      strains of mutant mice. The crystal structures of the IP3-binding core and N
      terminal suppressor sequence of the IP3 receptor have been identified. The IP3
      binding core's affinity to IP3 is similar among the three isoforms of IP3
      receptors; however, the N-terminal IP3-binding suppressor region is responsible
      for isoform-specific IP3-binding affinity tuning. Various pathways for the
      trafficking of IP3 receptors have been identified; for example, the ER forms a
      meshwork on which IP3 receptors move by lateral diffusion, and vesicular ER
      subcompartments containing IP3 receptors move rapidly along microtubules using a
      kinesin motor. Furthermore, IP3 receptor messenger RNA within messenger RNA
      granules also moves along microtubules. Recently, we discovered that IP3
      receptors play a crucial role in exocrine secretion. ERp44 works as a redox
      sensor in the ER and regulates IP3 type 1 receptor activity. IP3 receptor also
      releases IP3 receptor-binding protein released with IP3 (IRBIT). IRBIT is a
      pseudoligand for IP3 that regulates the frequency and amplitude of calcium
      oscillations through the IP3 receptor. IRBIT binds to pancreas-type sodium
      bicarbonate cotransporter 1, which is important for acid-base balance. Type 2 and
      3 double-deficient mice show a deficit in saliva and lacrimal and pancreatic
      juice secretion. Type 1 IP3 receptor influences brain-derived neurotrophic factor
      production.

PMID- 18813073
TI  - Innate immunity of the ocular surface and ocular surface inflammatory disorders.
AB  - Ocular surface epithelial cells selectively respond to microbial components and
      induce limited inflammation, whereas immune competent cells such as macrophages
      can recognize various microbial components through Toll-like receptors (TLRs),
      induce inflammation, and, thereby, exclude microbes. The difference between
      macrophages and ocular surface epithelial cells could be due to their
      dissimilarity in coexistence with commensal bacteria. The unique innate immune
      response of the ocular surface epithelium might contribute to its coexistence
      with commensal bacteria. Moreover, we suspect that some ocular surface
      inflammatory disorders might be caused by abnormality of the mucosal innate
      immunity. We considered the possibility that there is an association between
      Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN)--a severe variant
      of SJS--and a disordered innate immune response. In gene expression analysis of
      CD14 cells, we found that interleukin-4 receptor (IL-4R) gene expression was
      different between patients with SJS/TEN and normal control subjects upon
      lipopolysaccharide (LPS) stimulation: it was downregulated in the former and
      slightly upregulated in the latter. Furthermore, expression of mRNA specific for
      IkappaBzeta and interleukin (IL)-1alpha was lower in patients with SJS/TEN than
      in normal controls after 1-hour culture. We next performed single nucleotide
      polymorphism (SNP) association analysis of IL-4R, IkappaBzeta, and IL1alpha genes
      and TLR2 and TLR3--genes associated with innate immunity--in 80 Japanese patients
      with SJS/TEN and 160 Japanese healthy volunteers. IL4R SNP Gln551Arg (rs.1801275)
      (P = 0.0004), TLR3 rs.3775296T/G SNP (P = 0.0001) and TLR3 rs.3775290A/G SNP (P =
      0.009) showed a significant association with SJS/TEN. IkappaBzeta SNP
      rs.595788G/A showed a weak inverse association (P = 0.04). Genetic and
      environmental factors may play a role in an integrated etiology of SJS/TEN, and
      there is possibly an association between SJS/TEN and a disordered innate
      immunity.

PMID- 18813074
TI  - Recent advances in cultivated epithelial transplantation.
AB  - Currently, cultivated epithelial transplantation usually uses ex vivo-expanded
      epithelial cells, with or without biological carriers. Our group has carried out
      approximately 100 such procedures and has conducted research in this area. The
      results of a retrospective study indicate that cultivated limbal epithelial
      transplantation with amniotic membrane (AM) and airlifting may be beneficial at
      avoiding sight-threatening complications in patients with severe chronic
      cicatricial keratoconjunctivitis. Our experience in cultivated oral mucosal
      epithelial transplantation indicates that this technique is useful in achieving a
      stable ocular surface. However, the treatment for severe ocular surface diseases
      such as Stevens-Johnson syndrome remains unsatisfactory. In addition to using
      epithelial sheets with AM, we have developed a technique for generating carrier
      free sheets using fibrin sealants. These sheets seem to contain more
      differentiated epithelium than those obtained with AM while retaining similar
      levels of colony-forming progenitor cells. A clinical trial of this technique is
      currently underway. We have also generated epithelial sheets using as biological
      carrier silk fibroin film, which offers a more transparent medium than
      conventional sheets. In terms of isolation and cultivation of corneal epithelial
      stem/progenitor cells, we found that single murine limbal cells exhibited clonal
      growth and generated stratified epithelial sheets. We also reported that hypoxic
      culture (2%) enhanced proliferation in human limbal epithelial cells while
      inhibiting differentiation. This technique may help maintain progenitor cells
      during ex vivo expansion of epithelial cells. Although these advances are
      expected to improve clinical outcomes in patients with ocular surface disorders,
      further improvements, such as the development of cultivation methods that do not
      require 3T3 feeder cells or real-time assessment of cultivated sheets, are
      required in the near future.

PMID- 18813075
TI  - Cultivated corneal endothelial transplantation in a primate: possible future
      clinical application in corneal endothelial regenerative medicine.
AB  - PURPOSE: To review our attempt to devise a method of cultivated corneal
      endothelial transplantation using primates in which corneal endothelium, like
      that of humans, has low proliferative ability. METHODS: Monkey corneal
      endothelial cells (MCECs) were cultivated, with subcultures grown on collagen
      type I carriers. The corneal endothelia of 6 eyes of 6 monkeys were scraped
      intensively, after which cultivated MCEC sheets were inserted into the anterior
      chamber of 4 eyes. As controls, a collagen sheet without MCECs was transplanted
      in 1 eye of a monkey, and a suspension of cultivated MCECs was injected into the
      anterior chamber of 1 eye of another monkey. RESULTS: MCECs produced a confluent
      monolayer of closely attached hexagonal cells, which expressed both ZO-1 and Na-K
      adenosine triphosphatase. Early postoperative period MCEC sheets were attached to
      Descemet membrane, and corneal clarity was recovered. Six months after
      transplantation, MCEC-transplanted corneas remained clear, and closely attached
      hexagonal cells were observed. In 1 animal with longer observation, polygonal
      cells were observed by in vivo specular microscopy at a density of >2000
      cells/mm2 and remained >1600 cells/mm2 for < or =2 years. Control eyes showed
      irreversible bullous keratopathy throughout the observation period. CONCLUSIONS:
      Cultivated MCECs become attached to the transplanted eye and maintain a clear
      cornea < or =2 years postoperatively, suggesting that corneal endothelial cells
      of primates might have proliferative ability in vivo once they have been cultured
      and proliferated in vitro. Our monkey model constitutes an important step forward
      for regenerative medicine with possible future application in patients with
      corneal endothelial dysfunction.

PMID- 18813076
TI  - Osteo-odonto-keratoprosthesis in Japan.
AB  - Osteo-odonto-keratoprosthesis (OOKP) is a keratoprosthesis technique in which the
      patient's own tooth root is used to support an optical cylinder. It was invented
      by Strampelli in 1963 and modified and established by Falcinelli about 10 years
      later. This method is particularly useful for restoring sight in end-stage
      Stevens-Johnson syndrome (SJS) and ocular cicatricial pemphigoid (OCP). We
      started performing OOKP surgery in June 2003 supported by Dr Christopher Liu of
      Sussex Eye Hospital, Brighton, UK. Till now, we have performed 4 OOKP surgeries
      for end-stage SJS and OCP. We modified the original method by using artificial
      buccal mucous membranes to the bone and buccal mucous membrane defects for better
      wound healing. Case 1 was a 49-year-old woman (SJS), and the corrected visual
      acuity was 0.5 in 4 years 8 months. Case 2 was a 68-year-old woman (SJS), and the
      corrected visual acuity was 0.04 in 3 years 10 months. Case 3 was a 63-year-old
      man (SJS), and the corrected visual acuity was 0.1 in 3 years 2 months. Case 4
      was a 71-year-old woman (OCP), and the corrected visual acuity was 0.04 in 1 year
      3 months. Despite some minor optical cylinder troubles such as MRSA colonization,
      tilting, and buccal mucous coverage, their visual acuities were stable without
      any serious complications. It was demonstrated that OOKP is useful for visual
      rehabilitation and durable with minimum eye care for severe ocular surface
      diseases.

PMID- 18813077
TI  - Descemet stripping with automated endothelial keratoplasty for bullous
      keratopathies secondary to argon laser iridotomy--preliminary results and
      usefulness of double-glide donor insertion technique.
AB  - PURPOSE: Manipulation of the endothelial donor lamella in the anterior chamber
      during Descemet stripping with automated endothelial keratoplasty (DSAEK) is
      often difficult, especially in cases with bullous keratopathies (BK) secondary to
      argon laser iridotomy (ALI). We developed a novel nonfolding donor insertion
      technique using a Busin glide and an intraocular lens (IOL) sheet glide and
      evaluated post-DSAEK outcomes for ALI-induced BK using several insertion
      techniques. METHODS: Fourteen patients (mean age, 74.2 +/- 4.9 years) with ALI
      induced BK underwent DSAEK; simultaneous cataract surgery was performed in 12
      patients. Donor insertions were done by taco-folding (n = 4), spatula-assisted (n
      = 3), Busin glide-assisted (n = 2), and Busin glide/IOL glide-assisted methods (n
      = 5). Endothelial cell counts, postoperative visual acuity, induced astigmatism,
      and complications were examined over a mean follow-up period of 228.3 +/- 132.2
      days (range 58-458 days). RESULTS: In 1 case, DSAEK was converted to penetrating
      keratoplasty because of difficulties in donor insertion by the taco-folding
      method, resulting in vitreous prolapse. Overall, mean postoperative endothelial
      cell count was 1654.2 +/- 532.3 cells/mm2 (range 853-2610 cells/mm2), a 44.9%
      reduction compared with donor counts (mean 3003.3 +/- 425.5 cells/mm2). All
      patients reached acuity >20/40, with 3 (23.1%) reaching 20/20. Mean induced
      astigmatism in measurable cases was 0.53D +/- 0.38D. Although nonsignificant due
      to the small sample size, use of Busin glide with (37.9%) or without IOL glide
      (37.0%) tended to cause less endothelial damage than taco-folding (49.0%) or pull
      through with spatula (44.2%) at 3 months postoperatively. CONCLUSIONS: DSAEK is
      effective in eyes with ALI-induced BK. Our results suggest that insertion with a
      Busin glide is reliable and associated with less endothelial cell damage than the
      conventional taco-folding technique. Simultaneous use of IOL glide (Kobayashi
      double-glide method) to help prevent iris prolapse is our preferred insertion
      method for narrow-angle eyes.

PMID- 18813078
TI  - LASIK and the ocular surface.
AB  - Wound healing after LASIK sometimes compromises homeostasis of the ocular
      surface. Diffuse lamellar keratitis is a post-LASIK inflammatory condition in the
      interface that appears during the first week after LASIK. The etiology of diffuse
      lamellar keratitis is unknown, but the association with allergic reaction to
      detergent, bacteria, and other chemicals is suspected. The condition is mostly
      self-limiting. Topical and/or oral corticosteroids may be effective against stage
      2 disease, whereas flap lift and irrigation might be required in stage 3.
      Epithelial ingrowth occurs in about 1% of LASIK eyes. Although most cases heal
      spontaneously, some require surgical removal. There are 2 known mechanisms for
      epithelial ingrowth: epithelial invasion and epithelial implantation. Epithelial
      invasion grows in 2 distinct ways--outside invasion and flap epithelial invasion.
      The latter type is often seen after enhancement and may be treatment resistant.
      Patients with compromised attachment of corneal epithelium before LASIK may
      develop recurrent corneal erosion, which sometimes requires phototherapeutic
      keratectomy. Subepithelial opacity after viral infection, even long after
      infection, often recurs after LASIK and affects refraction and visual acuity.
      Topical corticosteroid may be effective to prevent recurrence. Dry eye is a
      common complication after LASIK. Although post-LASIK dry eye is usually
      temporary, some patients complain of severe symptoms that may negatively
      influence their satisfaction with the outcome. For example, functional visual
      acuity significantly decreases after LASIK. The possible mechanisms for post
      LASIK dry eye may be associated with loss of neurotrophic effect, damage of
      goblet cells, and altered corneal shape.

PMID- 18813079
TI  - Epithelial-immune cell interaction in dry eye.
AB  - Dry eye is a potent stimulus of both innate and adaptive immune systems. At the
      nexus of the dry eye inflammatory/immune response is the dynamic interplay
      between the ocular surface epithelia and the bone marrow-derived immune cells. On
      the one hand, ocular surface epithelial cells play a key initiating role in this
      inflammatory reaction. On the other hand, they are targets of cytokines produced
      by activated T cells that are recruited to the ocular surface in response to dry
      eye. This interaction between epithelial and immune cells in dry eye will be
      thoroughly reviewed.

PMID- 18813080
TI  - The enigma of nursing regulation.

PMID- 18813081
TI  - Nurse administrators and understanding the enigma of nursing regulation.

PMID- 18813082
TI  - Nursing regulation, the nurse licensure compact, and nurse administrators:
      working together for patient safety.
AB  - Maintaining the concept of states rights, boards of nursing responded to the need
      for removal of barriers in meeting nursing manpower needs. One mechanism to
      accomplish this end was the development of the Nurse Licensure Compact, a
      multistate nurse license structured in much the same way as driver's license
      compacts. Representatives of State Boards of Nursing developed model compact
      structure and rules which allow nurses licensed in their state of residence to
      practice in other participating states without having to obtain additional
      licenses. Monitoring of nurse licensure and disciplinary information is
      facilitated through Nursys (nurse system). Nurses, nurse administrators, and the
      public benefit from the experiences of the 23 states that have implemented the
      Nurse Licensure Compact.

PMID- 18813083
TI  - Credentialing the nurse practitioner in your workplace: evaluating scope for safe
      practice.
AB  - Nurse practitioner credentialing involves evaluation of scope of practice for
      appropriate fit within the facility and consistent with state practice law. This
      summary review provides information regarding resources to better understand
      nurse practitioner credentialing, scope, and practice issues. Topics for work
      place future consideration include the trend toward specialty practice and use of
      the title doctor in the clinical setting.

PMID- 18813084
TI  - Developing an advanced practice nursing credentialing model for acute care
      facilities.
AB  - Credentialing of advanced practice registered nurses (APRNs) in acute care
      settings is an essential practice, but care must be taken to ensure that full
      utilization of the scope of practice and capacity of APRNs is attained. The
      process of credentialing and privileging involves the verification of required
      education, licensure, and certification to practice as an APRN along with the
      recognition of the scope of the individual APRN's practice based on training,
      education, and practice setting. Nursing administrators are challenged with
      ensuring that APRNs are credentialed and privileged and that appropriate
      mechanisms exist within the institution for promoting recognition of the scope of
      practice of APRNs. This article reviews concepts related to the process of
      credentialing and privileging for APRNs, with special considerations to acute
      care settings. Important considerations are highlighted to ensure that the
      credentialing process for APRNs promotes practice within their scope of practice.

PMID- 18813085
TI  - Pain management: a regulatory issue.
AB  - Pain is a significant public health issue in the United States, and pain
      management has serious implications for the regulation of healthcare
      professionals. Pain management is recognized as important and integral to the
      practice of nursing. This article describes the legal and regulatory framework
      for pain management and identifies 4 specific regulatory issues. The public
      protection responsibility of boards of nursing is complicated by the need to
      appropriately concentrate on investigative, educational, and disciplinary work of
      the boards while not interfering with safe, effective pain management nursing
      care. Proactive board functions are suggested to support boards in maintaining
      this balance.

PMID- 18813086
TI  - Effects of the medication nursing assistant role on nurse job satisfaction and
      stress in long-term care.
AB  - Long-term care nurses continue to struggle with increasing workloads, fulfilling
      regulatory requirements and limited staffing resources. One method of impacting
      the workload is the introduction of the new medication nursing assistant (MNA)
      role to alleviate the nurse from prolonged time intervals spent administering
      medications. An early step in MNA role implementation is to evaluate its impact
      by comparing agencies using the MNA and those not using the role. This article
      presents findings from a mixed method study examining the efficacy of the MNA
      role in relationship to job satisfaction and the degree of perceived stress
      experienced by long-term care nurses. Ninety-one nurses employed at 2 large New
      Hampshire facilities responded. Findings offer empirical evidence supporting the
      use of the MNA to reduce job stress and increase satisfaction for licensed
      nurses. The MNA role is accepted by nurse leaders and viewed as a benefit.
      Findings also support a correlation between empowerment and decision making in
      the nursing environment with levels of nurse satisfaction.

PMID- 18813087
TI  - Confusion, concern, or complimentary function: the overlapping roles of the
      clinical nurse specialist and the clinical nurse leader.
AB  - Within the practice environment there are many demands to meet and many
      conflicting perspectives. The most recent example of this conflict is the
      polarity caused by the confusion and overlap between the established role of the
      clinical nurse specialist and the emerging role of the clinical nurse leader. The
      issues surrounding the confusion, concern, and potential for complimentary
      function are explored. The intent is to inform nursing leaders and provide points
      to use in making decisions regarding the roles and the focus on patient outcomes.

PMID- 18813088
TI  - Balancing Just Culture with regulatory standards.
AB  - Over the past decade, there has been much attention called to the reality of
      errors occurring in healthcare that jeopardize patient safety. Not only has this
      attention and reality caused angst and concern for persons and families that may
      require healthcare but it also causes significant angst and concern among care
      providers themselves. In response to the reality that 44,000 to 98,000 deaths
      occur annually because of medical error, regulatory organizations developed
      standards to achieve compliance with safe practice and delivery of care and to
      increase accountability. To promote more open, consistent, and reporting without
      fear of retribution, Just Culture philosophies are increasingly evident in
      healthcare organizations. These Just Culture organizations are described as
      taking a fair and balanced approach to event reporting, learning from mistakes,
      and holding persons and the organization accountable.

PMID- 18813089
TI  - Enhancing awareness of nursing regulation through a board of nursing orientation
      program for chief nursing officers.
AB  - Chief nursing officers are often in the position of making decisions that have
      regulatory implications. Therefore, it is imperative for these nurses to develop
      both an understanding of the complexities of regulation and a working
      relationship with the board of nursing. The Oregon State Board of Nursing (OSBN)
      implemented a full-day chief nurse orientation program in February 2007. Program
      components from all of the major areas within the OSBN's span of authority were
      included, and through these orientation sessions, chief nursing officers receive
      an overview of the OSBN's mission, a review of scopes of practice for licensees
      and certificate holders, information about investigation, mandatory reporting of
      nurses, the board's program for impaired nurses (Nurse Monitoring Program), and
      information on licensure directly from the board's staff. An evaluation of the
      program is performed through use of a pretest and a posttest as well as a course
      evaluation. Participants agreed that this was a beneficial program. Benefits
      could occur either through expansion of the program to middle management or
      through use of this program development model for development in other states.

PMID- 18813090
TI  - Professional boundaries violations: case studies from a regulatory perspective.
AB  - This article provides case studies in professional boundaries violations from a
      state regulatory perspective. All cases discussed are actual cases that occurred
      in the state of Ohio, based on complaints investigated by the Ohio Board of
      Nursing. The studies set forth basic factual information related to the boundary
      violation, relevant law and administrative regulations, and disciplinary
      outcomes. One can conclude that boundaries violations that result in licensure
      board disciplinary sanctions typically involve gross or egregious conduct rather
      than subtle or transitional zone conduct. These cases tend to involve recurring
      patterns that may be categorized as involving 2 factors: (1) high patient
      vulnerability and (2) prolonged patient contact. Often, the 2 patterns coalesce.
      Administrators, directors of nursing, and supervisors in these patient
      populations and in the settings discussed should be particularly mindful of
      potential boundary violation behavioral indicators.

PMID- 18813091
TI  - Male nurses and chemical dependency: masterminding the nursing environment.
AB  - Florida men in nursing who are chemically dependent represent a greater
      percentage of the total number of male nurses than female nurses who are
      chemically dependent. This study identifies characteristics of 9 men who
      completed the Florida Intervention Project for Nurses. All participants were
      interviewed independently and data were analyzed to determine common themes in
      their behaviors and relationships and how they successfully manipulated
      professional nursing systems to remain professionally active for prolonged period
      of time while impaired. A model of caring for nurses with professional impairment
      graphically depicted the interaction of 2 overarching themes of person and
      profession. The person theme had 3 subthemes of predetermined risk, altered
      values, and sensation-seeking behaviors. The profession theme had 6 subthemes of
      masterminding, professional heteronomy, getting caught, rehabilitation,
      spirituality, and the nurse becoming the nursed. Findings imply that chemical
      dependency among male nurses starts in childhood in an abusive family environment
      and continues throughout the educational process and into the work environment.
      Findings supporting diversion success include a lack of awareness of the signs
      and symptoms of impairment by supervisors, poor compliance to drug control
      procedures, and a common acceptance by peers that impaired men are clinically
      competent and clinical leaders. When these 3 situations are present, there is
      greater success in masterminding daily events to maintain undetected drug access.

PMID- 18813092
TI  - Education for worksite monitors of impaired nurses.
AB  - Boards of nursing sponsor programs, including those for alternatives to
      discipline, for recovering nurses. These programs rely on worksite monitors who
      are oftentimes other nurses or supervisors of nurses, to work with recovering
      nurses when they return to practice. The skills of these monitors vary with
      respect to understanding the monitor role and recognizing traits in chemical
      dependency and relapse. To determine the degree of content value and the best
      teaching method for monitors to learn program content, 17 currently active
      worksite monitors participated in a study to evaluate content value to 2 groups,
      new and experienced monitors, and to select the best method to teach 4 content
      topics. Results showed that current content was valued without necessary
      additions and that group instruction in urban areas was preferred over one-to-one
      instruction. Implementation of study outcomes yielded that issues of
      confidentiality made group instruction unsatisfactory.

PMID- 18813093
TI  - Why board of nursing disciplinary actions do not always yield the expected
      results.
AB  - One of the ways boards of nursing serve to protect the public health, safety, and
      welfare is by removing from practice those nurses who fail to meet recognized
      standards of care or otherwise pose a public threat. Self-reporting and discovery
      through criminal background checks and reports from the court system or other
      regulatory bodies represent only small numbers of those disciplined. Most
      complaints investigated by a board are reported by nursing administrators, either
      chief nursing officers or nurse managers. Frequently, the reporting nurses
      provide the board with information from their own investigation that identifies
      the problem and the cause and includes supporting evidence. Based on their own
      independent investigation, the reporting nurses often assume that the outcome of
      board action is a foregone conclusion. Without understanding all of the
      ramifications of disciplinary processes and the requirements to protect the
      rights of the nurse that are guaranteed under the US Constitution, the final
      outcome decision can be totally different than anticipated and thus disappointing
      to the reporting nurse administrator. They could perceive the decision as wrong,
      nonsupportive, and discounting the efforts made by the reporting nurse. This
      unhappiness with the outcome causes vulnerability in the major reporting source
      to a board, namely, the relationship between the board and the nurse
      administrator. An initial step in mitigating this vulnerability is a better
      understanding by nursing administrators of the legal procedures that guide
      disciplinary processes and boards providing timely feedback to reporting nurses
      on the disposition of cases.

PMID- 18813094
TI  - State-based licensure: are we regulating away the promise of telemedicine?
AB  - Thanks to telephones, telecommunication, and telehealth, nurses are practicing
      across national, continental, and-thanks to some National Aeronautics and Space
      Administration initiatives-even universal boundaries. One major barrier, however,
      stands in the way of widespread e-health implementation on national and
      international levels-state-based licensing.

PMID- 18813095
TI  - Failing the duty to report: disciplinary exposure risk for the chief nursing
      officer.

PMID- 18813096
TI  - Pig islet xenotransplantation into non-human primate model.
AB  - Allogeneic islet transplantation faces difficulties because (1) organ shortage is
      recurrent; (2) several pancreas donors are often needed to treat one diabetic
      recipient; and (3) the intrahepatic site of islet implantation may not be the
      most appropriate site. Another source of insulin-producing cells, therefore,
      would be of major interest, and pigs represent a possible and serious source for
      obtaining such cells. Pig islet grafts may seem difficult because of the species
      barrier, but recent reports demonstrate that pig islets may function in primates
      for at least 6 months. Pig islet xenotransplantation, however, must still
      overcome several hurdles before becoming clinically applicable. The actual
      consensus is to produce more preclinical data in the pig-to-primate model as a
      necessary requirement to envisage any pig-to-human transplantation of islets;
      therefore, a summary of the actual acquired knowledge of pig islet
      transplantation in primates seemed useful and is summarized in this overview.

PMID- 18813097
TI  - Calcineurin inhibitor sparing in renal transplantation.
AB  - Although calcineurin inhibitors (CNIs) are effective at preventing acute
      rejection, their long-term use is associated with nephrotoxicity that may
      compromise long-term renal allograft survival. Consequently, there is
      considerable interest in identifying immunosuppressive regimens that permit
      reduced exposure to CNIs while maintaining adequate immunosuppression.
      Introducing such strategies early after transplantation may mean that the
      development of CNI-associated nephrotoxicity could be minimized or prevented.
      Several CNI-sparing regimens have shown at least comparable efficacy with
      standard-dose CNI regimens. In particular, a regimen of mycophenolate mofetil
      (MMF), corticosteroids, interleukin-2 receptor antagonist induction, and low-dose
      tacrolimus from the time of transplantation provided superior renal function and
      a lower acute rejection rate than the same regimen but with low-dose cyclosporine
      or low-dose sirolimus, or standard-dose cyclosporine, MMF, and corticosteroids.
      The use of low-dose cyclosporine does not seem to eliminate nephrotoxicity in de
      novo renal transplant recipients. The early withdrawal of CNIs from MMF-based
      regimens generally improves renal function but has been associated with an
      increased risk of acute rejection, in particular when the levels of mycophenolic
      acid were not adjusted to maintain the same total level of immunosuppression.
      Research aiming to achieve the "best" balance of efficacy and toxicity of
      available immunosuppressive regimens continues.

PMID- 18813098
TI  - Antibody monitoring: a solid approach to predicting clinical outcome.

PMID- 18813099
TI  - Repairing spinal cord injury by cell transplantation.

PMID- 18813100
TI  - B cells in cluster or in a scattered pattern do not correlate with clinical
      outcome of renal allograft rejection.
AB  - BACKGROUND: The role of CD20+ B cells in renal allograft rejection has been
      reappreciated. Importantly, recent studies suggest a relation between CD20+ B
      cell aggregates and poorer clinical outcome. In the present study, we attempted
      to confirm these early reports in a tightly controlled patient population and to
      differentiate between scattered infiltrates and clusters of B cells. METHODS:
      Fifty-four biopsies from renal transplant recipients with acute rejection were
      immunostained for CD20, CD3, and C4d. All patients received similar
      immunosuppressive therapy. Response to therapy was defined as a decrease in serum
      creatinine level within 2 weeks to 125% or less of the value before the
      clinically diagnosed episode of allograft rejection. Late clinical outcome was
      defined in creatinine clearance between 8 and 12 months after the episode of
      acute rejection or in graft failure. RESULTS AND CONCLUSION: A significant
      correlation was observed between interstitial infiltrates of CD20+ cells and CD3+
      cells (r=0.720, P<0.001) suggesting that if B-cell infiltrates are present during
      rejection, they occur with T-cell infiltrates in a concurrent fashion. In
      contrast to previous reports, no relation was found between the number of CD20+
      cells, in aggregates or in a scattered interstitial pattern, and response to
      conventional therapy. Remarkably, CD3+T cell aggregates did predict a favorable
      renal outcome.

PMID- 18813101
TI  - Impact of VKORC1 haplotypes on long-term graft function in kidney
      transplantation.
AB  - BACKGROUND: Chronic allograft injury is the major cause of renal allograft loss
      after the first year of transplantation. Vitamin K epoxide reductase complex
      subunit 1 (VKORC1) haplotype combinations were found to be associated with the
      risk of developing vascular diseases. We aimed to study the effect of VKORC1
      haplotypes on long-term graft function in a cohort of kidney transplant
      recipients. METHOD: A total of 288 renal allograft recipients participated in the
      study. Long-term renal graft function was measured by the estimation of the
      glomerular filtration rate. VKORC1 C+1173T single nucleotide polymorphism
      (rs9934438) was used as a tagging single nucleotide polymorphism for VKORC1*2
      haplotype. RESULTS: Patients homozygous for VKORC1*2 haplotype showed less
      deterioration of renal graft function compared with the other patients (hazard
      ratio: 0.34, 95% confidence interval: 0.26-0.87, P=0.02). The same results were
      obtained in a multivariate analysis, where VKORC1 haplotypes showed to be an
      independent predictor of long-term graft function when adjusted to other
      variables contributing to long-term renal graft outcome. CONCLUSION: Our results
      suggest that VKORC1 haplotypes may play a role in the long-term renal allograft
      function. These findings need to be replicated in prospective clinical studies.

PMID- 18813102
TI  - Incidence and risk factors for hepatocellular carcinoma after solid organ
      transplantation.
AB  - BACKGROUND: Solid organ transplant recipients commonly are infected with
      hepatitis viruses, are immunosuppressed, and have other potential hepatocellular
      carcinoma (HCC) risk factors. METHODS: We studied de novo HCC incidence arising
      after transplant using U.S. registry data (223,660 recipients, 1987-2005). We
      used proportional hazards regression to identify HCC risk factors and calculated
      standardized incidence ratios (SIRs) to compare HCC risk with that in the general
      population. RESULTS: Based on 74 cases reported by transplant centers to the
      registry, HCC incidence was 6.5 per 100,000 person-years among kidney, heart, and
      lung (non-liver) recipients and 25 per 100,000 person-years among liver
      recipients. Hepatocellular carcinoma incidence among non-liver recipients was
      independently associated with hepatitis B surface antigenemia (hazard ratio [HR]
      9.7, 95% confidence interval [CI] 2.8-33), hepatitis C virus (HCV) infection (HR
      6.9, 95% CI 2.5-19), and diabetes mellitus (HR 2.8, 95% CI 1.2-6.6). Among liver
      recipients, HCC incidence was associated with advancing age (P<0.001), male sex
      (HR 4.6, 95% CI 1.4-16), HCV infection (HR 3.1, 95% CI 1.3-7.2), and diabetes
      mellitus (HR 2.7, 95% CI 1.2-6.2). Among non-liver recipients, overall HCC
      incidence was similar to the general population (SIR 0.8) but elevated among
      those with HCV (3.4) or hepatitis B surface antigenemia (6.5). Hepatocellular
      carcinoma incidence among liver transplant recipients was elevated overall (SIR
      3.4) and especially among those with HCV (5.0) or diabetes mellitus (6.2).
      CONCLUSIONS: Hepatocellular carcinoma incidence is elevated among liver
      transplant recipients and subsets of non-liver recipients. These risk factors
      indicate the need for improved control of viral hepatitis after solid organ
      transplantation.

PMID- 18813103
TI  - Posaconazole as salvage therapy in patients with invasive fungal infections after
      solid organ transplant.
AB  - BACKGROUND: The incidence of invasive fungal infections (IFIs) in solid organ
      transplant (SOT) recipients has increased during the past 20 years and is
      associated with significant morbidity and mortality. In this post hoc analysis of
      a large, open-label, multicenter study, we evaluated efficacy and safety of
      posaconazole, a new extended-spectrum triazole, as salvage therapy for IFIs in
      SOT recipients. METHODS: Twenty-three SOT recipients with proven or probable IFI
      and evidence of disease refractory to, or intolerant of, standard antifungal
      therapies received posaconazole oral suspension (40 mg/mL) 800 mg daily in
      divided doses. An independent, blinded data-review committee assessed patient
      diagnosis and outcome. RESULTS: Complete or partial response was documented in 13
      of 23 (57%) SOT recipients with proven or probable IFIs, including 1 of 2 (50%)
      refractory patients, 5 of 8 (63%) intolerant to prior therapy, and 7 of 13 (54%)
      who were both. Successes by type of IFI included 7 of 12 with invasive
      aspergillosis, 2 of 2 with invasive fusariosis, 1 of 1 with cryptococcosis, and 1
      of 2 with zygomycosis. Treatment-related adverse events (TRAEs) were reported in
      12 of 23 patients. Severe TRAEs occurred in 4 of 23 patients including increased
      levels of cyclosporine or tacrolimus requiring immunosuppressive dose adjustments
      in three patients and in one, termination of posaconazole. Severe TRAEs
      associated with renal and liver toxicities were uncommon. CONCLUSION:
      Posaconazole was well tolerated and effective against IFIs including invasive
      aspergillosis, zygomycosis, fusariosis, and cryptococcosis in SOT recipients
      intolerant of or failing other antifungal therapies. Calcineurin inhibitor levels
      should be closely monitored in patients treated concomitantly with posaconazole
      to avoid toxicity from drug interaction.

PMID- 18813104
TI  - Antirejection treatment in kidney transplant patients with BK viruria.
AB  - BACKGROUND: Kidney transplant recipients with BK virus nephropathy or viremia are
      generally treated with reduction of immunosuppression to facilitate virus
      eradication. METHODS: Prompted by biopsy findings interpreted as acute rejection,
      we administered intravenous bolus steroids to five patients with BK virus in the
      plasma (BKP) (group 1) and also tried other antirejection therapies in 13
      patients with BK virus in the urine (BKU) but no BKP (group 2). RESULTS: All
      group 1 patients had continued viremia, whereas two viruric patients in group 2
      developed viremia after therapy. Ultimately, after reduced immunosuppression both
      groups cleared BKP over 53+/-29 days and 50+/-6 days. BKU clearance was not
      consistently observed. One year postbiopsy, there were no graft failures (0%) in
      group 1 and 2 (15%) in group 2; however, suboptimal renal function was observed
      in 40% and 62%, respectively (P=0.6). CONCLUSION: Cautious antirejection
      treatment to patients with active BKP or BKU can lead to two possible outcomes:
      (a) reduction in serum creatinine that is seemingly consistent with a diagnosis
      of acute rejection and (b) lack of clinical response, which in the absence of
      overt BK nephropathy, makes it difficult to distinguish between refractory
      rejection and virus-induced tissue inflammation.

PMID- 18813105
TI  - The utility of a specific measure for heart transplant patients: reliability and
      validity of the Kansas City Cardiomyopathy Questionnaire.
AB  - BACKGROUND: Health-Related Quality of Life of patients with heart transplantation
      is an important variable; however, it has received little attention so far, and
      only two Spanish validated measurement instruments are available. The aim of our
      study was to validate the Spanish version of the Kansas City Cardiomyopathy
      Questionnaire (KCCQ) in heart transplant patients. METHODS: A prospective study
      was performed in 186 patients awaiting heart transplantation in nine transplant
      hospitals. Hundred transplant recipients filled out the KCCQ, the Euroqol 5-D
      (EQ5D), and the Short Form-36 (SF-36) Health Survey at pretransplant, after 3
      months, 6 months, and 1 year of follow-up. A complete set of sociodemographic and
      clinical data were also collected. The validity, reliability, sensitivity to
      change, and effect size were studied. Two questionnaires, the SF-36 and EQ5D,
      were used to evaluate the validity. RESULTS: Mean age of patients was 56.0 years,
      and 80.5% were men. Twenty-six percent had acute rejection. A five-dimensional
      factorial structure could be discerned. The questionnaire presented a Cronbach's
      alpha coefficient of more than 0.7. Correlations between the KCCQ and the other
      questionnaires and clinical variables were satisfactory. CONCLUSIONS: The KCCQ
      features adequate psychometric properties. The KCCQ offers several advantages
      over other questionnaires because it quantifies symptoms (frequency, severity,
      and stability) and it is much more sensitive to change, even when compared with
      the SF-36. The specific questionnaire for heart transplant patients is a useful
      and user-friendly instrument for measuring the Health-Related Quality of Life
      related to functional status, quality of life, and social limitation more
      accurately.

PMID- 18813106
TI  - Interstitial inflammatory lesions of the pulmonary allograft: a retrospective
      analysis of 2697 transbronchial biopsies.
AB  - BACKGROUND: Parenchymal and bronchial inflammatory and fibrotic lesions other
      than acute cellular rejection (ACR) and lymphocytic bronchiolitis are prevalent;
      however, the context in which they appear is unknown, and often no specific
      treatment is instigated. OBJECTIVES: To describe the prevalence, incidence and
      possible associations between commonly identified inflammatory and fibrotic
      lesions in the pulmonary allograft. METHODS: Retrospective chart review of all
      transbronchial biopsies performed within the first 2 years of 299 lung
      transplanted patients in the period 1996 to 2006. RESULTS: A total of 2697
      biopsies were evaluated corresponding to a mean of 6+/-2 (median 8) completed
      schedules per patient. Diffuse alveolar damage (DAD) was the second most common
      histological finding within the first 2 weeks after transplantation. The peak
      prevalence of bronchiolitis obliterans organizing pneumonia (BOOP) and
      interstitial pneumonitis occurred at 4 to 6 weeks, and 6 to 12 weeks,
      respectively. There was a steady increase in the cumulative proportion of
      patients with fibrosis and bronchiolitis obliterans, at each successive scheduled
      surveillance time point beyond 3 months posttransplantation. The strongest
      histological correlations were between ACR and lymphocytic bronchiolitis (OR 5.1,
      P<0.0001) or interstitial fibrosis (OR 3.2, P<0.0001). Patients with interstitial
      pneumonitis and pulmonary hemosiderosis were also more likely to demonstrate the
      finding of interstitial fibrosis (OR 3.0 and 3.7, P<0.0001, respectively). Acute
      cellular rejection was not associated with DAD, and patients with lymphocytic
      bronchiolitis were not more likely to demonstrate features of organizing
      pneumonia (DAD or BOOP). CONCLUSIONS: Histologic findings of ACR, lymphocytic
      bronchiolitis, BOOP, and interstitial pneumonitis were directly associated with
      the development of interstitial fibrosis and bronchiolitis obliterans.

PMID- 18813107
TI  - Acceptable donor-specific antibody levels allowing for successful deceased and
      living donor kidney transplantation after desensitization therapy.
AB  - BACKGROUND: The aims of this study were to determine the level of donor-specific
      antibody (DSA) that allows for successful transplantation after desensitization
      with IVIG and rituximab and to identify patients at risk for antibody-mediated
      rejection (AMR). METHODS: Pre- and posttransplant sera from 16 patients with DSA
      before desensitization were tested. Strength of DSA was determined by single
      antigen Luminex bead assay and results expressed as standard fluorescence
      intensity (SFI). T-cell flow crossmatch results were expressed as mean channel
      shifts (MCS). AMR was determined by biopsy and C4d deposition. RESULTS: Six had
      negative pretransplant flow crossmatches with a mean DSA of 8,805 SFI. Five had
      positive flow crossmatches (78-192 MCS) with mean DSA of 55,869 SFI. No patients
      in either group had AMR. Five had positive flow crossmatches (222-266 MCS) with
      mean DSA of 118,063 SFI. Three experienced AMR. The MCS and DSA levels for
      patients with AMR were significantly higher than patients without (P < or =
      0.001). For patients without complications (n=7), DSA remained less than 10(5)
      SFI and usually decreased to approximately 10(4) SFI posttransplant for both
      class I and II. For patients with AMR (n=3), predominant increases in class II
      DSA more than 10(5) SFI were observed. All three patients continue to have DSA
      approximately 10(5) SFI with stable creatinine after treatment for AMR.
      CONCLUSIONS: Approximately 63% of patients were transplanted with a positive flow
      crossmatch. The results show that patients with DSA more than 10(5) and FCM more
      than 200 MCS are at higher risk for AMR. Treatment of AMR improves renal function
      without significant changes in DSA.

PMID- 18813108
TI  - UL40 human cytomegalovirus variability evolution patterns over time in renal
      transplant recipients.
AB  - BACKGROUND: Human cytomegalovirus (HCMV) is the most common opportunistic
      pathogen infecting immunocompromised patients after transplantation. Although its
      immunomodulatory capacities and genomic variability participate in immune system
      evasion, they are poorly studied in clinical strains without culture
      amplification. One of HCMV immunomodulatory genes, UL40, confers HCMV-infected
      cells' protection from natural killer-mediated lysis through its encoded
      nonapeptide presented in the context of human leukocyte antigen-E. METHODS: In
      three renal transplant recipients with different HCMV serostatus, we aimed to
      evidence the co-evolution of mixtures of HCMV variants over time with sequencing
      and cloning of HCMV UL40 gene. RESULTS: Six months after renal transplantation in
      patient 1Bx, D+/R+, UL40 phylogenetic and bootscan analysis suggested the
      emergence of a recombination between two previous viral strains. In patient 8Bx,
      initially D+/R-, distribution of variants in five samples over 43 months was
      notably stable, with no visible emerging variants despite two renal engraftments
      and extended episodes of active infection. In patient 9Bx, also D+/R-,
      phylogenetic tree of viral variants revealed in the first sample a minor clone,
      confirmed by a specific polymerase chain reaction, related to the three
      subsequent dominant clones. CONCLUSIONS: In three HCMV-infected renal transplant
      recipients, we have evidenced different viral evolutive polymorphisms including
      point mutations, recombination, and occasionally suggesting the intervention of
      several HCMV strains or a quasispecies-like distribution. This variability could
      contribute to viral adaptability in pathogenesis.

PMID- 18813109
TI  - PD-L1/PD-1 signal deficiency promotes allogeneic immune responses and accelerates
      heart allograft rejection.
AB  - BACKGROUND: PD-L1, a ligand for programmed death 1 (PD-1), delivers a negative
      costimulatory signal to T cells and plays a critical role in the regulation of
      peripheral tolerance. METHODS: We used PD-L1(-/-) mice to evaluate the role of
      the PD-L1 signal on allogeneic immune responses in vivo and the underlying
      mechanisms. Heart transplantation was performed from PD-L1(-/-) donors or
      recipients in major histocompatibility complex fully mismatched mouse
      combinations. The immunologic function of allograft recipients was evaluated ex
      vivo by enzyme-linked immunospot, mixed lymphocytes reaction, cytotoxic T
      lymphocyte, and flow cytometry. RESULTS: Our results demonstrated that PD-L1(-/-)
      T cells proliferated vigorously under alloantigen stimulation, and also that the
      antigen-presenting cells (APCs) from PD-L1(-/-) mice exhibited a stronger
      allostimulatory activity compared with that in wild-type mice. Heart allografts
      were rejected at an accelerated rate in both PD-L1(-/-) donors and recipients.
      This was associated with significantly augmented donor specific T-cell
      proliferation and antidonor cytotoxic T lymphocyte activities, and enhanced Th1-
      or Th2-type immune responses of heart allograft recipients. CONCLUSIONS: Absence
      of PD-L1 input triggers a stimulatory signal to effector T cells and APCs,
      accelerating heart allograft rejection. Engagement of the PD-L1 signal on T cells
      or APCs may be necessary to induce transplant tolerance.

PMID- 18813110
TI  - Functional recovery of chronic paraplegic pigs after autologous transplantation
      of bone marrow stromal cells.
AB  - BACKGROUND: Bone marrow stromal cells (BMSC) transplantation offers promise in
      the treatment of chronic paraplegia in rodents. Here, we report the effect of
      this cell therapy in adult pigs suffering chronic paraplegia. METHODS: Three
      months after spinal cord injury, autologous BMSC in autologous plasma was
      injected into lesion zone and adjacent subarachnoid space in seven paraplegic
      pigs. On the contrary, three paraplegic pigs only received autologous plasma.
      Functional outcome was measured weekly until the end of the follow-up, 3 months
      later. RESULTS: Our present study showed progressive functional recovery in
      transplanted pigs. At this time, intramedullary posttraumatic cavities were
      filled by a neoformed tissue containing several axons, together with BMSC that
      expressed neuronal or glial markers. Furthermore, in the treated animals,
      electrophysiological studies showed recovery of the previously abolished
      somatosensory-evoked potentials. CONCLUSIONS: These findings confirm previous
      observations in rodents and support the possible utility of BMSC transplantation
      in humans suffering chronic paraplegia.

PMID- 18813111
TI  - Induction of alloanergy in human donor T cells without loss of pathogen or tumor
      immunity.
AB  - BACKGROUND: Human leukocyte antigen (HLA)-mismatched allogeneic hematopoietic
      stem cell transplantation (HSCT) is limited by acute graft-versus-host disease
      (aGvHD). Nonselective T-cell depletion effectively prevents severe aGvHD but
      profoundly impairs donor-derived immune reconstitution, increasing infection and
      disease relapse. The strategy of induction of alloantigen-specific
      hyporesponsiveness ("alloanergization") in donor bone marrow by allostimulation
      with costimulatory blockade before haploidentical transplantation has
      demonstrated early promise in reducing severe aGvHD. However, the differential
      effect of alloanergization on CD4+ and CD8+ donor T-cell subsets and the degree
      to which beneficial pathogen- and tumor-immune responses are retained have not
      been extensively examined. METHODS: We used an in vitro model of alloanergization
      by allostimulation of human donor T cells with irradiated unrelated recipient
      peripheral blood mononuclear cells and costimulatory blockade with humanized
      monoclonal anti-B7.1 and B7.2 antibodies. Residual alloresponses were assessed by
      proliferation (thymidine uptake, carboxyfluorescein diacetate succinimidyl ester
      dye dilution) and cytotoxicity assays. Retention of human herpes virus and tumor
      associated antigen (TAA)-specific immunity was measured with HLA-class I
      restricted pentamers, intracellular cytokine secretion, and CD107a assay using 5
      color flow cytometry. RESULTS: Alloanergization of HLA-mismatched donor T cells
      efficiently and selectively abrogated recipient-specific alloproliferation in
      both CD4+ and CD8+ cells while preserving functional CD4+ and CD8+ immune
      responses to clinically important human herpes viruses and to the TAA WT1.
      CONCLUSIONS: Retention of pathogen- and TAA-specific immunity after
      alloanergization demonstrates that this methodology, which is simple to apply,
      has potential to improve immune reconstitution while limiting alloreactivity
      after HLA-mismatched hematopoietic stem cell transplantation, and deserves
      additional evaluation in further human clinical trials.

PMID- 18813112
TI  - In vitro suppression of xenoimmune-mediated macrophage activation by human
      CD4+CD25+ regulatory T cells.
AB  - BACKGROUND: Macrophages are important effector cells in T cell-mediated xenograft
      rejection. The aim of this study was to determine whether CD4+CD25+ regulatory T
      cells (Tregs) were capable of suppressing macrophage activation in vitro.
      METHODS: Porcine cell or xenoantigen-primed human peripheral blood mononuclear
      cells, CD4+ T cell-depleted peripheral blood mononuclear cells, or CD14+
      macrophages plus autologous CD4+CD25- T cells were cultured with or without
      expanded autologous Tregs. Transwell cultures were used to separate the various
      components to determine the need for cell-cell contact. RESULTS: Pig cell primed
      CD14+ macrophages required the presence of CD4+CD25- T cells for activation and
      increased expression of CD40, interleukin-12, and tumor necrosis factor-alpha.
      This up-regulated expression of macrophage activation markers was reduced
      substantially in the presence of autologous Tregs. Coculture with Tregs did not
      alter macrophage viability but reduced the capacity of macrophages to stimulate
      proliferation of responder T cells. Tregs required direct contact with CD4+CD25-
      T cells to inhibit macrophage activation but activated macrophage phenotype was
      not altered by separating the stimulated human peripheral blood mononuclear cells
      or CD14+ macrophages from Tregs in a transwell system. Macrophages did not
      require direct cell contact with porcine stimulator cells for full activation by
      CD4+CD25- T cells. CONCLUSIONS: Human Tregs were able to suppress xenoantigen
      primed and CD4+ T-cell-mediated macrophage activation and antigen-presenting cell
      function. However, Tregs had no direct effect on macrophages in vitro.

PMID- 18813113
TI  - Treatment of chronic steroid-refractory graft-versus-host disease with low-dose
      rituximab.
AB  - Rituximab, an anti-CD20 chimeric monoclonal antibody, is widely used in
      hematologic malignancies and has been introduced as a therapeutic option in
      autoimmune disorders. In recent studies, rituximab has shown promising activity
      in steroid-refractory chronic graft-versus-host disease (cGvHD) at a weekly dose
      of 375 mg/m2. We now report on 13 subjects after peripheral blood stem-cell
      transplantation receiving low-dose rituximab (50 mg/m2) for steroid-refractory
      cGvHD and autoimmune disorders (membranous glomerulonephritis and immune
      thrombocytopenic purpura). The overall response rate was 69%, including two
      patients with complete responses. In accordance, we observed clearance of
      peripheral blood B cells even after the first dose of rituximab in four patients.
      We conclude that low-dose rituximab seems to be active and safe in intensively
      pretreated patients with steroid-refractory cGvHD.

PMID- 18813114
TI  - Selective effects of cyclosporine a on Th2-skewed dendritic cells matured with
      viral-like stimulus by means of toll-like receptors.
AB  - Successful prevention of allograft rejection and graft-versus-host disease with
      immunosuppression depends on controlled balance of Th1 and Th2 immune responses
      to establish tolerance and fight infection. Here, we have analyzed the effects of
      cyclosporine A (CsA) on the differentiation and functions of dendritic cells
      (DC2) that induce Th2 T cells. DC2 were differentiated from monocytes in the
      presence of CsA and were matured with viral or bacterial agonists (poly[I:C] or
      lipopolysaccharide). DC2 differentiation was not affected by CsA. In contrast,
      cytokine responses were altered with inhibition of interleukin-10 production in
      poly(I:C)-matured DC2. Surprisingly, interleukin-10 secretion by immature DC2 was
      increased after CsA treatment. Internalization was impaired in treated DC2, and
      CsA decreased the T-cell proliferative capacity of DC2 matured with poly(I:C),
      but not with lipopolysaccharide. In conclusion, CsA altered T-cell activating
      functions of DC2 with, notably, a regulatory phenotype for immature DC2 and
      opposite effects on poly(I:C)-matured cells.

PMID- 18813115
TI  - In response to: Benefit of neoral C2 monitoring in de novo cardiac transplant
      recipients receiving basiliximab induction.

PMID- 18813117
TI  - Hem-o-lok clip dislodgment causing death of the donor after laparoscopic living
      donor nephrectomy.

PMID- 18813118
TI  - Undifferentiated carcinoma with osteoclastic giant cells (UCOCGC) of the pancreas
      associated with the familial atypical multiple mole melanoma syndrome (FAMMM).
AB  - The familial atypical multiple mole melanoma (FAMMM) syndrome is caused by a
      germline mutation of p16. More than 90% of the sporadic pancreatic carcinomas
      contain genetic alterations that inactivate p16. Patients with the FAMMM syndrome
      have an increased risk of developing pancreatic cancer. Ductal adenocarcinoma is
      the most common cancer of the pancreas and the one encountered in patients with
      FAMMM syndrome. Undifferentiated carcinoma with osteoclastic giant cells, also
      referred to as UCOCGC of the pancreas, is a rare variant of pancreatic cancer. An
      UCOCGC of the pancreas associated with FAMMM syndrome is described in this
      report. Molecular analysis confirmed a germline p16-Leiden deletion in the
      UCOCGC, accompanied by somatic loss of heterozygosity of the second p16 allele,
      and absence of p16 protein expression in the neoplastic cells. It is the first
      case reported and it provides additional evidence that UCOCGC can be considered
      as a variant of conventional ductal adenocarcinoma of the pancreas.

PMID- 18813119
TI  - Primary angiosarcoma of the breast: clinicopathologic analysis of 49 cases,
      suggesting that grade is not prognostic.
AB  - Mammary angiosarcoma is a rare neoplasm, accounting for about 0.05% of all
      primary malignancies of the breast. It is currently believed that histologic
      grading of mammary angiosarcomas plays an important role in prognostication.
      Forty-nine cases of primary angiosarcoma of the breast were retrieved from our
      files. Clinical details and follow-up information were obtained from referring
      pathologists and clinicians, and by chart review. All statistics were performed
      using Fisher exact test and only P<0.05 was considered significant. Recurrence
      free survival and overall survival curves were established using Statistica
      software version 5.5 (StatSoft Inc). All patients were female with ages ranging
      from 15 to 74 years (mean 41.5, median 40). Peak incidence was between the ages
      of 30 and 50 years. All tumors examined were located within breast parenchyma
      with or without minor cutaneous involvement. The right side was more commonly
      affected than the left side (66% vs. 29.5%). Tumor was bilateral at presentation
      in 2 cases (4.5%). Tumor size varied from 0.7 to 25 cm (mean 6.7, median 5). Most
      patients presented with a palpable, painless mass. Two patients had a history of
      prior radiation treatment for breast carcinoma. Histologically, primary tumors
      were graded using Rosen's 3-tier system: 17 tumors (35.4%) as low grade, 17
      (35.4%) as intermediate grade, and 14 (29.2%) as high grade. Forty-six patients
      were treated surgically, 11 underwent chemotherapy, and 12 patients received
      radiotherapy. Follow-up was available in 41 patients (83.7%, median duration 29
      mo). Ten patients (24.4%) showed evidence of local recurrence within 11 to 60
      months (median 36) after diagnosis. Twenty-four patients (58.5%) thus far have
      developed metastases, which were most commonly to lung, liver, skin, and bone.
      Time interval between diagnosis and metastasis ranged from 2 to 144 months
      (median 34). Eighteen patients (44%) so far have died of disease and 1 died of
      presumably disseminated breast carcinoma. Five patients (12.2%) are alive with
      disease and 15 patients (36.6%) are alive with no evidence of disease.
      Statistical analysis evaluating correlation between tumor grade and size, and
      rate of local recurrence, metastasis, and death owing to disease showed no
      significant difference among tumors of different grades. The median recurrence
      free and overall survival rates for the entire cohort were 2.8 and 5.7 years,
      respectively. In conclusion, mammary angiosarcoma is a rare disease that affects
      relatively younger patients. This tumor seems to have an overall similar clinical
      course as other types of angiosarcoma arising in skin or soft tissue; it carries
      a moderate risk of local recurrence, and a high risk of metastasis and death. In
      this large series, there is no correlation between histologic grade and patient
      outcome, more in line with angiosarcomas at other sites.

PMID- 18813120
TI  - False positive labeling of prostate cancer with high molecular weight
      cytokeratin: p63 a more specific immunomarker for basal cells.
AB  - Occasional nonspecific staining of prostate cancer cells with high molecular
      weight cytokeratin (HMWCK) can lead to false-negative diagnoses. We compared p63
      and HMWCK immunostaining to check their specificity for basal cell
      identification. Out of 6887 prostate cancer cases sent in consultation to one of
      the authors over 1.5 years, we identified 22 (0.3%) cases with HMWCK labeling of
      cancer cells, including 20 needle biopsies and 2 transurethral resections of
      prostate (TURP). Cases were sent in consultation because of the confusing
      immunostaining pattern, where prostate cancer cells labeled with HMWCK at the
      outside institutions. In 6 cases, p63 immunostains were also received from the
      outside institution, whereas in the remaining 16 cases p63 immunohistochemistry
      was performed at our institution. In 14 cases, we used either an extra destained
      hematoxylin and eosin slide or a negative control slide for immunohistochemistry
      with antibodies to p63, and in the 2 remaining cases submitted unstained slides
      were used. The Gleason scores were 3+3=6 in 20 cases and 4+4=8 in 2 cases. The
      size of the tumor on needle biopsy ranged from 0.5 to 6.0 mm (mean 1 mm) and on
      the 2 TURP cases consisted of 44 and 68 cancer glands, respectively. The number
      of tumor cells positive for HMWCK in each of the needle biopsy cases ranged from
      3 to 48 (mean 13 cells), whereas on the 2 TURP cases 26 and 10 cells were labeled
      with HMWCK. Corresponding stains for p63 on the same cases were negative in 18
      cases. In 3 of 4 cases, p63 labeled 1, 1, and 2 tumor cells, respectively. The
      fourth case had 5 positive cells on p63 staining with 4 positive for HMWCK. To
      assess whether overstaining was a factor, we evaluated the intensity of HMWCK
      staining in the basal cells of the benign glands, which was moderate in 6 and
      strong in 16 cases. The cytoplasm of benign secretory cells showed focal weak
      (n=3), diffuse weak (n=1), and focal moderate (n=2) staining for HMWCK. HMWCK
      labeling of prostate cancer cells is uncommon and does not seem to be solely
      attributable to overstaining. p63 is a more specific marker for basal cells than
      HMWCK, with less labeling of tumor cells. Recognition of this phenomenon and
      performing stains for p63 when it occurs can help prevent underdiagnosing
      prostatic carcinoma.

PMID- 18813121
TI  - Hyalinizing trabecular tumors of the thyroid gland are almost all benign.
AB  - In 1987, Carney et al reported 11 thyroid tumors with the following features:
      circumscription or encapsulation, trabecular architecture with intratrabecular
      hyalin and colloid, polygonal and spindle cells, nuclei with frequent grooves and
      cytoplasmic inclusions, occasional psammoma bodies, and a low mitotic rate. The
      neoplasms did not recur or metastasize during a follow-up period that averaged 10
      years, and they were titled hyalinizing trabecular adenomas. Subsequently, the
      nuclear features of the neoplasm led to the introduction of 2 modified titles for
      it, hyalinizing trabecular tumor and hyalinizing trabecular neoplasm. Later,
      discovery of RET/PTC mutations in the tumor resulted in it being designated as a
      type of papillary thyroid carcinoma. We studied 119 neoplasms of the type
      outlined, collected over a 20-year period, for invasion, recurrence and
      metastasis, and obtained follow-up in 96% of the cases. One hundred eighteen
      tumors showed no evidence of aggressive behavior (capsular, vascular, and
      parenchymal invasion), local recurrence, or metastasis. One tumor showed vascular
      and capsular invasion, and pulmonary metastasis. We conclude that the
      overwhelming majority of hyalinizing trabecular tumors of the thyroid behave as
      benign neoplasms and that, at this time, hyalinizing trabecular adenoma is the
      most appropriate title for them.

PMID- 18813122
TI  - Indeterminate cell tumor: a rare dendritic neoplasm.
AB  - Indeterminate cell tumor (ICT) is a rare neoplastic dendritic cell disorder that
      has been poorly defined due to its rarity and poorly understood histogenesis and
      pathogenesis. It is characterized by a proliferation of dendritic cells, which
      mimic Langerhans cells immunophenotypically (positive for CD1a and S-100
      protein), but lack Birbeck granules characteristic of Langerhans cells. The
      clinical, morphologic, immunophenotypic, and ultrastructural features of 5 ICT
      cases are reported in an attempt to further define ICT and to examine the
      postulated relationship between indeterminate cells and Langerhans cells. Four of
      5 patients were females, and 4 of 5 were older than 68 years. Three of 5 patients
      had cutaneous lesions, whereas 2 presented with cervical lymph node involvement.
      Two patients had a possible association with lymphoma: first patient had a
      history of progressive follicular lymphoma that led to patient's demise and the
      second patient had unexplained systemic lymphadenopathy and died 1 week after the
      biopsy. All 5 ICT cases expressed CD1a and S-100 protein, but lacked Langerin
      expression and Birbeck granules ultrastructurally. Interestingly, a t(14;18) was
      detected by fluorescence in situ hybridization in the ICT cells of the patient
      with previous follicular lymphoma and a monoclonal kappa light chain gene
      rearrangement was detected by polymerase chain reaction in the patient with
      systemic lymphadenopathy. In both cases, there was no morphologic or
      immunophenotypic evidence of a concurrent B-cell lymphoma. In conclusion, ICT is
      a rare neoplasm that can occur de novo or in association with a B-cell lymphoma,
      possibly as a result of B-cell dedifferentiation caused by relatively unknown
      mechanisms. Finally, Langerin immunostaining may be used as a surrogate marker
      for the ultrastructural demonstration of Birbeck granules, the absence of which
      represents a strong diagnostic criterion for ICT.

PMID- 18813123
TI  - Parathyroid lipoadenomas and lipohyperplasias: clinicopathologic correlations.
AB  - Parathyroid lipoadenomas and lipohyperplasias are rare histologic variants with
      both an increase in stromal fat and parenchyma. We report the most comprehensive
      single institution series of lipoadenomas and lipohyperplasias to date and review
      the literature. Eight lipoadenomas and 3 lipohyperplasias (27 y period) were
      reviewed. The mean age was 60.3 years (range: 50 to 77 y) with a female
      predilection (1.75:1). The most common symptoms on presentation were fatigue
      (55.6%) and bone/joint pain (44.4%). Only 1 patient was euparathyroid. Ultrasound
      localized lipoadenomas in 50% of tested cases whereas sestamibi was successful in
      71.4%. Despite increased stromal fat (median: 50%), the weight and the appearance
      of large, occasionally nodular expansions of parathyroid parenchyma within the
      fatty stroma distinguished lipoadenomas and lipohyperplasias from normal
      parathyroid tissue; none of the cases were misclassified as normal on frozen
      section. Mean weight for lipoadenomas was 1553 mg (range: 173 to 4587 mg),
      whereas the mean weight for lipohyperplasia glands was 389.1 mg. Variant
      morphologies included follicular patterned, oxyphil predominant, and thymic
      elements (thymolipoadenoma). In 1 lipohyperplasia case, not all glands were
      involved. Oil Red O stains showed decreased intracytoplasmic lipid in most cases.
      Median follow-up was 9.2 months (range: <1 to 51 mo). Only 1 lipohyperplasia
      patient had persistent hypercalcemia, but was asymptomatic. Lipoadenomas and
      lipohyperplasias are clinically similar and as histologically diverse as their
      conventional counterparts. Lipoadenomas are more difficult to localize
      preoperatively by imaging. Despite the potential difficulty at frozen section,
      accurate weight documentation and recognition of key histologic features diminish
      this challenge.

PMID- 18813124
TI  - Endocervical adenocarcinomas with ovarian metastases: analysis of 29 cases with
      emphasis on minimally invasive cervical tumors and the ability of the metastases
      to simulate primary ovarian neoplasms.
AB  - Most endocervical adenocarcinomas ( approximately 90%) are high-risk human
      papillomavirus (HPV)-related neoplasms, with the remainder being unrelated to
      HPV; both types infrequently metastasize to the ovaries. Clinicopathologic
      features of 29 cases of synchronous and metachronous endocervical and ovarian
      tumors (26 HPV-related, 3 unrelated to HPV) were analyzed. In 18 cases, the
      cervical tumors were clearly invasive; these included 5 clinically evident tumors
      diagnosed before the ovarian metastases (immediately preoperatively to 7 y), 11
      clinically unsuspected tumors diagnosed concurrently in specimens obtained for
      evaluation of ovarian/pelvic masses, 1 case with concurrent clinically evident
      cervical and ovarian masses, and 1 clinically occult tumor diagnosed subsequent
      to the ovarian metastasis. In 11 cases, the cervical tumors were more limited;
      these included 5 tumors comprised predominantly of adenocarcinoma in situ with
      small foci of superficial invasion ("microinvasive carcinomas") diagnosed before
      the ovarian metastases (3 mo to 7 y) and 6 tumors comprised of extensive
      adenocarcinoma in situ lacking unequivocally recognizable stromal invasion
      diagnosed before (9 mo to 7 y, n=4), concurrently with (n=1), or subsequent to
      (n=1) the ovarian metastases. Fifteen cervical tumors involved lower uterine
      segment corpus endometrium or endomyometrium, including 4 tumors that were
      minimally invasive or not recognizably invasive in the cervix. The ovarian tumors
      ranged in size from 2.1 to 30.0 cm (mean/median=12.7/13.5); they were unilateral
      in 19 cases (65.5%) and 12 of these were unilateral and 10 cm or greater. In 26
      cases, including the 19 unilateral tumors, the ovarian tumors exhibited
      "borderlinelike," confluent glandular, cribriform, and/or villoglandular patterns
      simulating primary ovarian atypical proliferative (borderline) tumors or well
      differentiated carcinomas; these patterns were pure in 24 and admixed with minor
      infiltrative foci in 2. The ovarian tumors had features typical of metastases
      (bilateral and infiltrative) in only 3 cases. In all HPV-related cases the paired
      endocervical and ovarian tumors contained identical HPV types, establishing the
      ovarian tumors as metastases. Endocervical adenocarcinomas, including
      microinvasive forms and some not recognizably invasive, have the potential to
      metastasize to the ovaries; extension into the lower uterine segment/corpus
      endometrium may be a risk factor, with retrograde uterine/transtubal spread as a
      possible mechanism.

PMID- 18813125
TI  - Chromophobe renal cell carcinoma: histomorphologic characteristics and evaluation
      of conventional pathologic prognostic parameters in 145 cases.
AB  - The aggregate literature suggests that chromophobe renal cell carcinoma (RCC) is
      biologically a tumor of low malignant potential with reported 5-year and 10-year
      survival rates of 78% to 100% and 80% to 90%, respectively. The conventional
      prognostic parameters that determine the outcome of the tumors that progress
      remain to be fully characterized. Clinicopathologic features of 145 cases were
      correlated with outcome. The mean age of the patients was 59 years (range, 27 to
      82) and the male to female ratio was 1.1:1. Most tumors were well circumscribed
      and averaged 8.0 cm (range, 1.0 to 30.0 cm); multifocality and bilaterality were
      present in 8% and 3% of patients. Sixty (41%) were eosinophilic variant (greater
      than 80% eosinophilic cells), 18 (12%) were classic type (greater than 80% pale
      cells), and 67 (46%) were mixed (containing variable admixture of pale and
      eosinophilic cells). A subset of eosinophilic chromophobe RCC contained or had
      areas similar to renal oncocytomas. These tumors tended to be more commonly
      bilateral (11%) and multifocal (22%) and were not associated with necrosis or
      sarcomatoid change. Sarcomatoid change was present in 12/145 (8%) tumors. By
      histologic grade, 1%, 19%, 74%, 6% were Fuhrman nuclear grade 1, 2, 3, and 4.
      Nineteen percent, 21%, 28%, 13%, 4%, 1%, and 3% were pT (2002) stage pT1a, pT1b,
      pT2, pT3a, pT3b, pT3c, and pT4 tumors. Two percent tumors were pN1 at
      presentation and 2.8% tumors were M1 at presentation. Follow-up (1 to 182 mo,
      mean 48 mo, median 37 mo) was available in 123 cases. Disease progression (local
      recurrence 4, metastasis 15, and/or death 10) was seen in 20 patients. In
      univariable analysis, tumor size (P=0.025), pT stage (P<0.001), broad alveolar
      architecture (P=0.012), Fuhrman nuclear grade (P<0.001), microscopic tumor
      necrosis (P=0.001), vascular invasion (P=0.020), and sarcomatoid change (P< or
      =0.001) were associated with progression. A multivariable Cox regression model
      revealed sarcomatoid change (P=0.013, estimated relative hazard 4.7), microscopic
      necrosis (P=0.020, relative hazard=3.5), and pT stage (P=0.025, relative hazard
      3.4) as independent predictors of aggressive chromophobe RCC. Although the large
      majority of chromophobe RCCs have a favorable prognosis, a distinct subset of
      patients progress. The pT stage of tumor, tumor necrosis, and sarcomatoid change
      all predict aggressive phenotype of chromophobe RCC. The adverse presence of
      these features in a nephrectomy specimen with chromophobe RCC warrants active
      surveillance, and these patients may be candidates for adjuvant therapies as they
      become available.

PMID- 18813126
TI  - Protein expression of matriptase and its cognate inhibitor HAI-1 in human
      prostate cancer: a tissue microarray and automated quantitative analysis.
AB  - Recent studies have suggested that matriptase, a transmembrane serine protease
      and its cognate inhibitor hepatocyte growth factor activator inhibitor-1 (HAI-1)
      are important in the progression of many cancers. Limited quantitative data are
      available on these proteins in prostate cancer. To validate the roles of
      matriptase and HAI-1 in prostate cancer and its progression, a prostate cancer
      tissue microarray was constructed. The tissue microarray includes 41 localized
      prostate cancers (Pca_local), 18 aggressive prostate cancers, 18 metastatic
      prostate cancers, 24 benign prostate hyperplasias, 18 high-grade intraepithelial
      neoplasias (HGPIN), and 41 benign prostate tissues. The cellular expression
      levels of matriptase and HAI-1 were quantified using automated quantitative
      analysis. We found that matriptase expression levels were significantly higher in
      Pca_local (P<0.0001) and HGPIN (P<0.05) compared with benign prostate tissue.
      Matriptase levels were significantly decreased in metastatic cancer when compared
      with all other tissue types (P<0.05). Compared with benign prostate tissue, HAI-1
      expression levels were significantly higher in all proliferative prostate
      diseases (benign prostate hyperplasia, HGPIN, localized and aggressive cancers,
      and metastases) (P<0.001); yet, no significant differences were found in HAI-1
      expression levels among the diseased tissue types. These results suggest that an
      increase of matriptase may be useful as a marker for detection of Pca_local,
      whereas a decrease of matriptase expression may signal prostate cancer
      progression. HAI-1 seems to be a marker of prostate epithelial cell
      proliferation.

PMID- 18813127
TI  - Histologic, immunohistochemical, and molecular classification of 52 IPMNs of the
      pancreas.
AB  - BACKGROUND: Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas
      account for approximately 5% of pancreatic neoplasms. Prognosis is superior to
      that of pancreatic invasive ductal carcinoma. IPMNs reveal a variety of
      epithelial linings expressing different mucin staining patterns and may progress
      along different oncogenic pathways. MATERIALS AND METHODS: Fifty-two IPMNs were
      studied for expression of MUC1, MUC2, p16, p21, HER2, cyclin D1, and p53 protein
      and for mutations in K-ras, HER2, p53, EGFR, and BRAF genes. The cases were
      evaluated for dysplasia, presence of invasion, and morphology of lining
      epithelium. RESULTS: Twenty-six IPMNs appeared intestinal (IN). Five were low, 12
      moderate, and 9 high grade. K-ras mutations were found in 15, EGFR mutations in
      2, and BRAF mutation in 1. Seven cases were pancreaticobiliary (PB) and all
      showed moderate to high-grade dysplasia. Six K-ras mutations and 2 p53 mutations
      were found in PB tumors. p53 mutations were in cases with high-grade dysplasia.
      Nineteen IPMNs demonstrated a gastric foveolar (GF) pattern. The majority of GF
      cases had low or moderate dysplasia. Sixteen revealed K-ras mutations and 1 case
      each demonstrated a HER2 or p53 mutation. Five IPMNs revealed invasive
      adenocarcinoma, including a colloid carcinoma from an IN type epithelium.
      CONCLUSIONS: IN pattern IPMNs were the most common. Mixed histology was common. K
      ras mutations were most common, but did not correlate with dysplasia. p53
      mutations were seen in 6% of cases (only in GF and PB subtypes). A HER2 mutation
      was found in a GF IPMN. EGFR and BRAF mutations were restricted to IN IPMNs.
      These findings suggest the possibility of alternate pathways for carcinogenesis
      between epithelial subtypes of IPMNs.

PMID- 18813128
TI  - Frequent expression of glypican-3 in Merkel cell carcinoma: an
      immunohistochemical study of 55 cases.
AB  - The pathologic diagnosis of Merkel cell carcinoma (MCC) is mainly based on
      routine morphology and a characteristic cytokeratin 20 (CK20) immunohistochemical
      staining pattern. However, about 10% to 15% of MCCs are reportedly CK20 negative
      and about 10% to 20% of MCCs have only focal CK20 positivity. We aimed to study
      glypican-3 (GPC3) expression in MCC and to compare it with CK20 expression in
      MCC. Immunohistochemical expression of GPC-3, CK20, and CD23 were studied in 55
      cases of MCC and 21 cases of noncutaneous small cell neuroendocrine carcinoma
      (SCNC), including 10 cases of pulmonary SCNC and 11 cases of nonpulmonary SCNC.
      The results of GPC3 expression in these tumors were then compared with that of
      CK20. Of the 55 cases, 39 were positive for GPC3 (70.9%). Seventy-seven percent
      of the positive MCCs (30/39) showed GPC3 immunoreactivity in > or = 30% tumor
      cells. Of the 55 cases, 53 were positive for CK20 (96%); 49 of them showed CK20
      immunoreactivity in > or = 30% tumor cells. All MCC cases were either positive
      for both GPC3 and CK20 (37 cases) or at least 1 of the markers (18 cases, 16 CK20
      only and 2 GPC3 only). In addition, we studied GPC3 and CK20 expression in 10
      cases of pulmonary SCNC and 11 cases of nonpulmonary SCNC. Three of ten pulmonary
      SCNC and 5 of 11 nonpulmonary SCNC expressed GPC3. All pulmonary SCNC and 9 of 11
      nonpulmonary SCNC were negative for CK20. All cases of MCC and SCNC were negative
      for CD23. In conclusion, GPC3 is frequently expressed in SCNC of various origins,
      in particular in MCC, which, in combination with CK20, may represent another
      useful marker in the diagnosis of MCC.

PMID- 18813129
TI  - Improving hospital preparedness for radiological terrorism: perspectives from
      emergency department physicians and nurses.
AB  - BACKGROUND: Hospital emergency department (ED) clinicians will play a crucial
      role in responding to any terrorist incident involving radioactive materials. To
      date, however, there has been a paucity of research focusing specifically on ED
      clinicians' perspectives regarding this threat. METHODS: At the request of the
      Centers for Disease Control and Prevention, researchers at the University of
      Alabama at Birmingham conducted a series of 10 focus groups (total participants,
      77) with ED physicians and nurses at hospitals in 3 US regions. Participants
      considered a hypothetical "dirty bomb" scenario and discussed their perceptions,
      concerns, information needs, preferred information sources, and views of current
      guidance and informational materials. RESULTS: Study participants consistently
      expressed the view that neither EDs nor hospital facilities are sufficiently
      prepared for a terrorist event involving radioactive materials. Key clinician
      concerns included the possibility of the hospital being overwhelmed, safety of
      loved ones, potential staffing problems, readiness problems, and contamination
      and self-protection. Participants also expressed a need for additional
      information, strongly disagreed with aspects of current response guidance, and in
      some cases indicated they would not carry out current protocols. CONCLUSIONS:
      This study is the first to examine the views, perceptions, and information needs
      of hospital ED clinicians regarding radiological terrorism. As such, the findings
      may be useful in informing current and future efforts to improve hospital
      preparedness.

PMID- 18813130
TI  - Smoking habits, waist circumference and coronary artery disease risk
      relationship: the PRIME study.
AB  - INTRODUCTION: Abdominal obesity is an important risk factor for coronary artery
      disease (CAD). The extent to which tobacco exposure influences the effect of
      abdominal adiposity on CAD incidence remains uncertain. Therefore, the goal of
      this study was to assess the effects of tobacco exposure on CAD risk associated
      with abdominal obesity. METHODS: A cohort of 9763 men, aged 50-59 years, without
      known CAD was followed 10 years for CAD events. Risk factors were recorded using
      a questionnaire, a clinical examination, including waist circumference (WC) and
      waist-to-hip ratio (WHR) and biological measurements. Cox regression was used for
      statistical analyses. RESULTS: During follow-up, there were 659 incident CAD
      events. BMI, WC, WHR, blood pressure, cholesterol, high-density lipid cholesterol
      and triglycerides, physical activity and alcohol intake varied across smoking
      exposure categories. The incidence of CAD increased across tertiles of waist
      circumference in never (5.1, 6.1 and 7.2 CAD events/1000 in first, second and
      third tertiles of WC distribution, respectively), former (6.6, 7.8 and 9.3
      events/1000, across tertiles) and current smokers (9.4, 11 and 13.1 events/1000,
      across tertiles). After adjusting for age, centre, educational level, alcohol
      intake and physical activity, the relative risk of CAD was 1.28 (1.08-1.51) for 1
      standard deviation increase of WC in never smokers, 1.23 (1.08-1.38) in former
      smokers and 1.14 (1.00-1.29) in current smokers. Similar results were observed
      for WHR. No evidence for heterogeneity among tobacco exposure strata for both WC
      and WHR was observed. CONCLUSION: In conclusion, the relative risk of CAD
      associated with abdominal obesity is homogeneous in never, former and current
      smokers. Therefore, smokers with abdominal obesity are at high absolute risk of
      CAD.

PMID- 18813131
TI  - The use of role-play to enhance medical student understanding of genetic
      counseling.
AB  - PURPOSE: Advances in genetics have meant that genetic testing will become
      increasingly relevant to all health care fields. It is therefore important that
      all physicians have increased genetic education in their training, including in
      the medical school curriculum. METHODS: To address this need, we used role
      playing in an effort to enhance understanding of genetic counseling. Students
      were given the option of participating in a mock genetic counseling session
      whereby they would play the role of a patient receiving genetic test results. All
      students received questionnaires on their attitudes and knowledge about genetic
      counseling. Those who participated answered additional questions regarding
      effectiveness of the project. RESULTS: Of 88 students who returned presimulation
      questionnaires, 19 opted to participate in the mock session, and 15 participants
      returned postsimulation questionnaires. There was no significant difference
      between participant and nonparticipant questionnaire responses. However, all
      participants agreed that role-play was effective in helping them understand
      genetic counseling and testing. Most participants also commented that the session
      helped them understand the importance of referral for genetic counseling and the
      impact of test results. CONCLUSIONS: The project proved overall valuable in
      improving medical student understanding of genetic counseling and may be applied
      to a variety of medical education settings to improve patient care.

PMID- 18813132
TI  - Policy considerations in designing a fragile X population screening program.

PMID- 18813133
TI  - Reciprocal translocations: tracing their meiotic behavior.
AB  - PURPOSE: Segregation and interchromosomal effect studies have been performed in
      reciprocal translocation carriers by sperm-fluorescent in situ hybridization
      reporting a great heterogeneity. The divergences have been attributed to the
      particular cytogenetic characteristics of each rearrangement. Nevertheless, there
      is no consensus in the factors that are responsible for such variability. The
      purpose of this study was to determine which cytogenetic features influence in
      the segregation and interchromosomal effect outcome. METHODS: Segregation and
      interchromosomal effects analyses were performed in 14 reciprocal translocation
      carriers, selected because they presented very different cytogenetic features
      regarding the tetravalent pairing geometry. In each segregation study, a
      customized combination of probes was used to identify all the segregation
      products. In the interchromosomal effect study, we used a triple-color
      fluorescent in situ hybridization for chromosomes X, Y, and 18. RESULTS: A
      preferential segregation pattern with a gradually decreasing production of
      Alternate, Adjacent I, Adjacent II, and 3:1 segregation was observed in the
      segregation analysis. Some specific features have been observed to influence this
      distribution: size of the translocated and centric segments and the presence of
      centromeres from acrocentric chromosomes in the center of the cross.
      Aneuploidy/diploidy screening revealed increased frequencies of numerical
      anomalies in seven carriers. CONCLUSIONS: Our data suggest that reciprocal
      translocations display a more homogeneous behavior than described in the
      literature. The interchromosomal effects represent an additional source of
      imbalances in these carriers.

PMID- 18813134
TI  - Genetic determinants of variable metabolism have little impact on the clinical
      use of leading antipsychotics in the CATIE study.
AB  - PURPOSE: To evaluate systematically in real clinical settings whether functional
      genetic variations in drug metabolizing enzymes influence optimized doses,
      efficacy, and safety of antipsychotic medications. METHODS: DNA was collected
      from 750 patients with chronic schizophrenia treated with five antipsychotic
      drugs (olanzapine, quetiapine, risperidone, ziprasidone, and perphenazine) as
      part of the Clinical Antipsychotic Trials of Intervention Effectiveness study.
      Doses for each of the medicines were optimized to 1, 2, 3, or 4x units in
      identically appearing capsules in a double-blind design. We analyzed 25 known
      functional genetic variants in the major and minor metabolizing enzymes for each
      medication. These variants were tested for association with optimized dose and
      other relevant clinical outcomes. RESULTS: None of the tested variants showed a
      nominally significant main effect in association with any of the tested
      phenotypes in European-Americans, African-Americans, or all patients. Even after
      accounting for potential covariates, no genetic variant was found to be
      associated with dosing, efficacy, overall tolerability, or tardive dyskinesia.
      CONCLUSION: There are no strong associations between common functional genetic
      variants in drug metabolizing enzymes and dosing, safety, or efficacy of leading
      antipsychotics, strongly suggesting merely modest effects on the use of these
      medicines in most patients in typical clinical settings.

PMID- 18813135
TI  - Fragile X syndrome detection in newborns-pilot study.
AB  - PURPOSE: Fragile X syndrome is the most common form of hereditary intellectual
      disability. Detection of the fragile X phenotype in the prepubertal period is
      very difficult, and early detection might assist in early developmental
      intervention and reproductive counseling. A pilot study was conducted to
      establish the feasibility of newborn screening for fragile X syndrome. METHODS: A
      prospective study was done contacting mothers postdelivery in two hospitals in
      upstate South Carolina from 2005 to 2006. With their permission, blood samples
      were obtained from the male infants via heelstick and analyzed. RESULTS: A total
      of 1,459 newborns were tested, and 5 abnormal results were obtained. The results
      included one sex chromosome aneuploidy (47, XXY), two premutations, and two full
      mutations. CONCLUSIONS: Our study establishes the potential feasibility of such a
      screening process. However, more complete studies assessing a larger population
      and risk-benefit analyses are necessary before any universal application of this
      test. Our detection rate for fragile X syndrome (1:730) was inexplicably greater
      than anticipated but likely represents a chance occurrence among the small number
      of infants tested.

PMID- 18813136
TI  - Recreational genomics; what's in it for you?

PMID- 18813137
TI  - Putting it all behind: long-term psychological impact of an inconclusive DNA test
      result for breast cancer.
AB  - PURPOSE: An inconclusive DNA-result for breast cancer may leave women with
      uncertainty that cannot be relieved. We assessed the influence of beliefs women
      held about their inconclusive DNA-result on psychological well-being and whether
      women had been able to put the period of DNA testing behind them. METHODS: In
      total, 215 women completed a baseline and a follow-up questionnaire 2.5 till 7
      years after DNA test disclosure. Within the group of 147 women who received an
      inconclusive result (either a personal result or the result of an affected family
      member) multiple regression analyses were applied to investigate the relevance of
      women's personal beliefs. RESULTS: Personal beliefs and ambivalence about an
      inconclusive DNA-result were associated with cancer-related worry and distress (P
      < 0.05). Moreover, these beliefs seemed to be an especially strong predictor of
      whether women had been able to leave the period of DNA testing behind them, even
      after controlling for all measures of psychological distress (P < 0.001).
      DISCUSSION: Psychological distress measures may provide an important but
      incomplete picture of how women make sense of an inconclusive DNA-result. These
      findings underscore the importance of discussing counselees' beliefs and
      expectations openly to enhance well-being and adaptation on the long term.

PMID- 18813138
TI  - Factors influencing the referrals in primary care of asymptomatic patients with a
      family history of cancer.
AB  - PURPOSE: To describe the events and the reasoning that led UK general
      practitioners to make a direct referral to a genetics clinic for a family history
      of cancer. METHODS: Asymptomatic patients with a family history of cancer and
      general practitioners who had referred them to a genetics clinic were eligible to
      participate. Semi-structured interviews incorporating a self-completed
      questionnaire were conducted with the general practitioners. Questions about the
      referral had to be framed in general terms as few general practitioners could
      remember the index case. Individual face-to-face interviews based on a topic
      guide were conducted with the patients. RESULTS: Thirty-six of 54 eligible
      general practitioners and 71 asymptomatic patients with a family history of
      cancer completed the study. General practitioners adopted a reactive rather than
      proactive role in the provision of genetic services for asymptomatic patients
      with a family history of cancer. Most general practitioners favored cancer
      diagnostic clinics as a referral pathway, and made a referral to genetics only
      when patients or a hospital doctor specifically requested this. More
      idiosyncratic approaches to the referral decision were also encountered. Updating
      of skills and knowledge in genetics remained a low priority despite acknowledged
      inadequacies. CONCLUSIONS: Referral guidelines that are practicable in the
      context of a busy primary care clinic need to be developed if primary care
      practitioners are to play the major role desired for them in genetics.

PMID- 18813139
TI  - The Evaluation of Genomic Applications in Practice and Prevention (EGAPP)
      Initiative: methods of the EGAPP Working Group.
AB  - The Evaluation of Genomic Applications in Practice and Prevention (EGAPP)
      Initiative, established by the National Office of Public Health Genomics at the
      Centers for Disease Control and Prevention, supports the development and
      implementation of a rigorous, evidence-based process for evaluating genetic tests
      and other genomic applications for clinical and public health practice in the
      United States. An independent, non-federal EGAPP Working Group (EWG), a
      multidisciplinary expert panel selects topics, oversees the systematic review of
      evidence, and makes recommendations based on that evidence. This article
      describes the EGAPP processes and details the specific methods and approaches
      used by the EWG.

PMID- 18813140
TI  - Arrhythmias in patients receiving enzyme replacement therapy for infantile Pompe
      disease.
AB  - PURPOSE: Enzyme replacement therapy in infants with Pompe disease prolongs
      survival, decreases cardiomegaly, and improves muscle function. Because ectopy
      has been previously described in these patients, we sought to determine the
      prevalence and types of arrhythmias. METHODS: Thirty-eight children with
      infantile Pompe disease received enzyme replacement therapy in two open-label,
      multicenter, international, clinical trials. Data were reviewed on a
      retrospective basis. The corrected QT interval, ejection fraction, and indexed
      left ventricular mass were measured on a scheduled basis from electrocardiograms
      and echocardiograms. Arrhythmias were identified and characterized from
      electrocardiograms, ambulatory electrocardiograms, and point-of-care monitoring.
      Electrocardiogram and echocardiogram measurements were compared in children with
      and without arrhythmias. RESULTS: Seven children (18%) experienced arrhythmias.
      The QT interval, ejection fraction, indexed left ventricular mass, and rate of
      reduction of indexed left ventricular mass were not statistically different in
      those seven versus the other 31 children. Two children with life-threatening
      arrhythmias had among the highest combined baseline maximum indexed left
      ventricular mass and QT interval. Their arrhythmias occurred during severe
      metabolic stress from noncardiac illness. CONCLUSIONS: There was a high incidence
      of arrhythmias in our cohort. The relationship of arrhythmias with enzyme
      replacement therapy, myocardial fibrosis, or simply longer survival is unknown.
      Therefore, further characterization of specific arrhythmia risk factors and
      continued vigilance regarding screening for arrhythmias in children receiving
      enzyme replacement therapy is warranted.

PMID- 18813141
TI  - Effect of preoperative residual hearing on speech perception after cochlear
      implantation.
AB  - OBJECTIVE: To assess the effect of substantial preoperative residual hearing on
      speech perception outcomes in adult cochlear implant recipients. SETTING:
      Tertiary care academic referral center. METHODS: Twenty-nine patients with
      substantial preoperative residual hearing underwent cochlear implantation. Twenty
      one implant recipients matched for age and duration of hearing loss, but without
      preoperative residual hearing, served as controls. Postoperative speech
      perception was assessed using City University of New York sentence, consonant
      nucleus-consonant, and hearing in noise test in quiet and in noise (+10 dB signal
      to noise ratio) tests at 1, 3, 6, and 12 months after fitting. RESULTS: After
      implantation, there were no significant differences between groups for any of the
      tests administered. The mean change in speech perception abilities from baseline
      was significantly greater for the control patients than those with substantial
      preoperative residual hearing at a number of the test intervals across the
      various conditions. Moreover, at both 1 and 3 months, some patients in the
      residual hearing group had speech perception scores that were worse than their
      preoperative values. Ultimately, all of the patients with substantial residual
      hearing surpassed their preoperative performance. DISCUSSION: Patients with
      substantial preoperative residual hearing can gain significant benefit from
      cochlear implantation. Although the degree of improvement in these individuals is
      somewhat more modest than for those patients without preoperative residual
      hearing, the outcomes are still excellent. That there were no significant
      differences between the patient groups suggests that having substantial residual
      hearing before implantation does not provide a measurable performance advantage
      for electrical stimulation. Patients with substantial residual hearing who are
      contemplating cochlear implantation should be counseled regarding a possible
      initial decline in speech perception performance.

PMID- 18813142
TI  - Safety and outcomes of outpatient pediatric otolaryngology procedures at an
      ambulatory surgery center.
AB  - OBJECTIVES: To determine the safety and outcomes of outpatient pediatric
      otolaryngology procedures performed at an ambulatory surgery center (ASC).
      METHODS: Retrospective review of all pediatric otolaryngology cases performed at
      a freestanding, outpatient ASC of a tertiary care, academic children's medical
      center from 2000 to 2007. RESULTS: Of all cases, 4979 (55%) were otolaryngology
      procedures. Twelve surgeons and 10 pediatric anesthesiologists staffed the cases;
      no residents/fellows were involved. The case breakdown is as follows: 2045
      (41.1%) myringotomy and tympanostomy tube; 1438 (28.9%) adenoidectomy (with
      tympanostomy tube placement and/or turbinectomy); 880 (17.7%) tonsillectomy (with
      or without adenoidectomy). According to American Society of Anesthesiologist
      (ASA) classification: 84.2% were ASA I, 15.1% ASA II, 0.7% ASA III. There were
      nine unanticipated outcomes: four postadenotonsillectomy and one
      postadenoidectomy bleeds (three requiring reoperation the same day), two patients
      with low psuedocholinesterase levels, one postadenotonsillectomy patient
      requiring overnight monitoring, and one patient with an incidental finding of a
      subglottic mass. Preoperative ASA status on these nine patients was 7 (78%) ASA
      I, 2 (22%) ASA II. CONCLUSIONS: Pediatric otolaryngology procedures constitute
      significant volume at our ASC. Surgery at our ASC is extremely safe with a rate
      of unanticipated outcomes of 0.2%--a comparison not available in the literature.
      Pediatric otolaryngology procedures performed with a highly skilled team at an
      outpatient ASC result in high quality and safe surgery.

PMID- 18813143
TI  - Heterosexual anal sex: part of an expanding sexual repertoire?

PMID- 18813145
TI  - Surgery of the human cerebrum. Vascular malformations. Selected bibliography.

PMID- 18813144
TI  - What about the men?

PMID- 18813146
TI  - Role of frameless stereotaxy in the surgical treatment of cerebral arteriovenous
      malformations: technique and outcomes in a controlled study of 44 consecutive
      patients.
AB  - OBJECTIVE: To describe a frameless stereotactic technique used to resect cerebral
      arteriovenous malformations (AVMs) and to determine whether frameless stereotaxy
      during AVM resection could decrease operative times, minimize intraoperative
      blood losses, reduce postoperative complications, and improve surgical outcomes.
      METHODS: Data for 44 consecutive patients with surgically resected cerebral AVMs
      were retrospectively reviewed. The first 22 patients underwent resection without
      stereotaxy (Group 1), whereas the next 22 patients underwent resection with the
      assistance of a frameless stereotaxy system (Group 2). RESULTS: The patient
      characteristics, AVM morphological features, and percentages of preoperatively
      embolized cases were statistically similar for the two treatment groups. The mean
      operative time for Group 1 was 497 minutes, compared with 290 minutes for Group 2
      (P = 0.0005). The estimated blood loss for Group 1 was 657 ml, compared with 311
      ml for Group 2 (P = 0.0008). Complication rates, residual AVM incidences, and
      clinical outcomes were similar for the two groups. CONCLUSION: Frameless
      stereotaxy allows surgeons to 1) plan the optimal trajectory to an AVM, 2)
      minimize the skin incision and craniotomy sizes, and 3) confirm the AVM margins
      and identify deep vascular components during resection. These benefits of
      stereotaxy were most apparent for small, deep AVMs that were not visible on the
      surface of the brain. Frameless stereotaxy reduces the operative time and blood
      loss during AVM resection.

PMID- 18813147
TI  - Multimodality treatment of giant intracranial arteriovenous malformations.
AB  - OBJECTIVE: Giant arteriovenous malformations (AVMs) (i.e., those greater than 6
      cm at maximum diameter) are difficult to treat and often carry higher treatment
      morbidity and mortality rates than do smaller AVMs. In this study, we reviewed
      the treatment, angiographic results, and clinical outcomes in 53 patients with
      giant AVMs who were treated at Stanford between 1987 and 2001. METHODS: The
      patients selected included 20 males (38%) and 33 females (62%). Their presenting
      symptoms were hemorrhage (n = 20; 38%), seizures (n = 18; 34%), headaches (n = 8;
      15%), and progressive neurological deficits (n = 7; 13%). One patient was in
      Spetzler-Martin Grade III, 9 were in Spetzler-Martin Grade IV, and 43 were in
      Spetzler-Martin Grade V. The mean AVM size was 6.8 cm (range, 6-15 cm). AVM
      venous drainage was superficial (n = 7), deep (n = 20), or both (n = 26). At
      presentation, 31 patients (58%) were graded in excellent neurological condition,
      17 were graded good (32%), and 5 were graded poor (9%). RESULTS: The patients
      were treated with surgery (n = 27; 51%), embolization (n = 52; 98%), and/or
      radiosurgery (n = 47; 89%). Most patients received multimodality treatment with
      embolization followed by surgery (n = 5), embolization followed by radiosurgery
      (n = 23), or embolization, radiosurgery, and surgery (n = 23). Nineteen patients
      (36%) were completely cured of their giant AVMs, 90% obliteration was achieved in
      4 patients (8%), less than 90% obliteration was achieved in 29 patients (55%) who
      had residual AVMs even after multimodality therapy, and 1 patient was lost to
      follow-up. Of the 33 patients who either completed treatment or were alive more
      than 3 years after undergoing their most recent radiosurgery, 19 patients (58%)
      were cured of their AVMs. The long-term treatment-related morbidity rate was 15%.
      The clinical results after mean follow-up of 37 months were 27 excellent (51%),
      15 good (28%), 3 poor (6%), and 8 dead (15%). CONCLUSION: The results in this
      series of patients with giant AVMs, which represents the largest series reported
      to date, suggest that selected symptomatic patients with giant AVMs can be
      treated successfully with good outcomes and acceptable risk. Multimodality
      treatment is usually necessary to achieve AVM obliteration.

PMID- 18813148
TI  - Image-guided transsylvian, transinsular approach for insular cavernous angiomas.
AB  - OBJECTIVE: Surgical treatment of cavernomas arising in the insula is especially
      challenging because of the proximity to the internal capsule and lenticulostriate
      arteries. We present our technique of image guidance for operations on insular
      cavernomas and assess its clinical usefulness. METHODS: Between 1997 and 2003,
      with the guidance of a frameless stereotactic system (BrainLab AG, Munich,
      Germany), we operated on eight patients who harbored an insular cavernoma.
      Neuronavigation was used for 1) accurate planning of the craniotomy, 2)
      identification of the distal sylvian fissure, and, finally, 3) finding the exact
      site for insular corticotomy. Postoperative clinical and neuroradiological
      evaluations were performed in each patient. RESULTS: The navigation system worked
      properly in all eight neurosurgical patients. Exact planning of the approach and
      determination of the ideal trajectory of dissection toward the cavernoma was
      possible in every patient. All cavernomas were readily identified and completely
      removed by use of microsurgical techniques. No surgical complications occurred,
      and the postoperative course was uneventful in all patients. CONCLUSION: Image
      guidance during surgery for insular cavernomas provides high accuracy for lesion
      targeting and permits excellent anatomic orientation. Accordingly, safe exposure
      can be obtained because of a tailored dissection of the sylvian fissure and
      minimal insular corticotomy.

PMID- 18813149
TI  - Surgical risks associated with the management of Grade I and II brain
      arteriovenous malformations.
AB  - OBJECTIVE: Grade I and II arteriovenous malformations (AVMs) have been considered
      safe to resect. However, unoperated low-grade AVMs have not been considered in
      previously reported series. The aim of this study was to examine all cases, both
      operated and unoperated, to identify any characteristics of low-grade AVMs that
      comprise a subgroup that might pose a relatively higher risk. METHODS: A
      prospectively enrolled AVM database included 237 patients in Spetzler-Martin
      Grade I or II. These patients were analyzed on the basis of demographic
      characteristics, angiographic and magnetic resonance imaging features, clinical
      presentation, method of treatment, and outcome. RESULTS: Surgery was performed in
      220 patients in Spetzler-Martin Grade I or II. Seventeen patients did not undergo
      treatment because of poor neurological condition (six patients), patient refusal
      (nine patients), and perceived surgical difficulty (AVM size approaching 3 cm
      adjacent to Broca's area) (two patients). The overall surgical morbidity rate was
      0.9%, and the mortality rate was 0.5%. Adverse outcomes occurred in 1 (0.6%) of
      180 patients with AVMs located away from eloquent cortex and in 2 (5%) of 40
      patients with AVMs adjacent to eloquent cortex. None of 28 surgical patients with
      deep venous drainage had an adverse outcome. All 219 patients who survived
      surgery underwent postoperative angiography that confirmed cure. No postoperative
      hemorrhage has occurred in 1143 patient-years of follow-up (mean follow-up, 5.3
      yr). CONCLUSION: When considering adverse outcome in the surgical series of Grade
      I and II AVMs alone, no statistical difference between non-eloquently located
      AVMs (0.6%) and eloquently located AVMs (5% adverse outcome) can be detected.
      However, consideration of all Grade I and II AVMs, both surgical and nonsurgical,
      may prove that a difference in outcome exists between these two groups masked by
      case selection. Generalization of the chances of adverse outcomes to all Grade I
      and II AVMs (both operated and unoperated) suggests that the risk of performing
      surgery on noneloquent brain in our series was 0.6% and that in eloquent brain
      could have been as high as 9.5%, had all such patients undergone surgery.

PMID- 18813150
TI  - Operation of arteriovenous malformations assisted by stereoscopic navigation
      controlled display of preoperative magnetic resonance angiography and
      intraoperative ultrasound angiography.
AB  - OBJECTIVE: To study the application of navigated stereoscopic display of
      preoperative three-dimensional (3-D) magnetic resonance angiography and
      intraoperative 3-D ultrasound angiography in a clinical setting. METHODS:
      Preoperative magnetic resonance angiography and intraoperative ultrasound
      angiography are presented as stereoscopic images on the monitor during the
      operation by a simple red/blue technique. Two projections are generated, one for
      each eye, according to a simple ray casting method. Because of integration with a
      navigation system, it is possible to identify vessels with a pointer. The system
      has been applied during operations on nine patients with arteriovenous
      malformations (AVMs). Seven of the patients had AVMs in an eloquent area.
      RESULTS: The technology makes it easier to understand the vascular architecture
      during the operation, and it offers a possibility to identify and clip AVM
      feeders both on the surface and deep in the tissue at the beginning of the
      operation. All 28 feeders identified on the preoperative angiograms were
      identified by intraoperative navigated stereoscopy. Twenty-five were clipped at
      the beginning of the operation. The other three were clipped at a later phase of
      the operation. 3-D ultrasound angiography was useful to map the size of the
      nidus, to detect the degree of brain shift, and to identify residual AVM.
      CONCLUSION: Stereoscopic visualization enhances the surgeon's perception of the
      vascular architecture, and integrated with navigation technology, this offers a
      reliable system for identification and clipping of AVM feeders in the initial
      phase of the operation.

PMID- 18813151
TI  - Cerebral cavernous malformations associated with venous anomalies: surgical
      considerations.
AB  - OBJECTIVE: Once thought to be rare entities, mixed cerebrovascular malformations
      with pathological features of more than one type of malformation within the same
      lesion are now being recognized with increasing frequency. Their identification
      generates several hypotheses about common pathogenesis or causation-evolution
      among different types of lesions and leads to controversial discussion on
      therapeutic strategies. METHODS: Fifteen patients drawn from a consecutive series
      of 58 patients harboring cavernous malformations (25.9%) were found to have an
      associated venous malformation (VM). Three (33.3%) of the first 9 patients, in
      whom the large draining vein of the VM had been left untouched at previous
      interventions, developed recurrent and/or de novo lesions. RESULTS:
      Histopathological analysis, interestingly, revealed that the new lesions were
      different in nature (three arteriovenous angiomas in two patients, a capillary
      telangiectasia in one patient). During extirpation of the new malformation, the
      draining vein of the VM in these three patients could be coagulated without any
      adverse events. Coagulation and dissection of the draining vein of the associated
      VM was performed in six more patients of our series, and this has prevented
      development of new lesions up to now. CONCLUSION: Our results are in favor of the
      hypothesis that the draining vein of a VM is the actual underlying abnormality of
      mixed vascular malformations. Causing flow disturbances and having the potential
      for hemorrhages, the VM seems to promote the development of new adjacent
      malformations. Thus, permanent cure of associated malformations might depend on
      the surgical treatment of the VM. We present a preliminary personal series and a
      thorough review of the literature.

PMID- 18813152
TI  - Surgery of cerebral arteriovenous malformations.
AB  - Despite remarkable progress, the microsurgical extirpation of cerebral
      arteriovenous malformations (AVMs) even by experienced neurosurgeons is not
      always easy or safe. This article focuses on how to render AVM surgery safer, and
      offers strategies and tactics for avoiding perilous bleeding and preserving
      postoperative neurological function. Our treatment strategies and surgical
      techniques are offered from the operating surgeon's perspective. An understanding
      of pathophysiology of cerebral AVMs is important for their appropriate surgical
      treatment. Sophisticated neuroimaging techniques and scrupulous
      neurophysiological examinations alert to possible complications, and improved
      surgical approaches help to minimize the sequelae of unanticipated complications.
      At the early stage of cerebral AVM surgery, extensive dissection of the sulci,
      fissures, and subarachnoid cistern should be performed to expose feeders, nidus,
      and drainers. Problems with the surgery of large and/or deep-seated lesions are
      exacerbated when arterial bleeding from the nidus continues even after all major
      feeders are thought to have been occluded. We routinely place catheters for
      angiography at the surgery of complex AVMs to find missing feeding arteries or to
      identify the real-time hemodynamic status of the lesion. Temporary clip
      application on feeders and less coagulation of the nidus is necessary to control
      intranidal pressure and to avoid uncontrollable bleeding from the nidus and
      adjacent brain. Intraoperative navigation images superimposed on tractography
      images can provide us with valuable information to minimize neurological
      deficits. Deeper insight into AVM nature and into events that occur during AVM
      surgery as well as the inclusion of molecular biological approaches will open new
      horizons for the safe and effective treatment of AVMs.

PMID- 18813153
TI  - Surgery of the human cerebrum. Intrinsic tumors. Selected bibliography.

PMID- 18813154
TI  - Incidence and clinical evolution of postoperative deficits after volumetric
      stereotactic resection of glial neoplasms involving the supplementary motor area.
AB  - OBJECTIVE: We report the incidence and clinical evolution of postoperative
      deficits and supplementary motor area (SMA) syndrome after volumetric
      stereotactic resection of glial neoplasms involving the posterior one-third of
      the superior frontal convolution. We investigated variables that may be
      associated with the occurrence of SMA syndrome. METHODS: The postoperative
      clinical status of 27 consecutive patients who underwent resection of SMA gliomas
      was retrospectively reviewed. Neurological examination results were recorded 1
      day, 1 week, 1 month, and 6 months postoperatively. The extent of tumor
      resection, the percentage of SMA resection, violation of the cingulate gyrus, and
      operative complications were tabulated. RESULTS: The overall incidence of SMA
      related deficits was 26% (7 of 27 patients), with 3 patients having complete SMA
      syndrome and 4 patients having partial SMA syndrome. Two additional patients
      (7.5%) had other postoperative deficits, including one with mild facial weakness
      and one with transient aphasia. The resection of low-grade gliomas was associated
      with a higher incidence of SMA syndrome, an outcome that likely reflects more
      complete removal of functional SMA cortex in this subset of patients.
      Intraoperative monitoring localized the precentral sulcus within the
      preoperatively defined tumor volume in 6 (22%) of 27 patients, thereby precluding
      gross total resection. All 27 patients had excellent outcomes at the 6-month
      follow-up examination. CONCLUSION: When the resection of SMA gliomas is limited
      to the radiographic tumor boundaries, the incidence and severity of SMA syndrome
      may be minimized. With the use of these resection parameters, patients with high
      grade SMA gliomas are unlikely to experience SMA syndrome. These findings are
      helpful in the preoperative counseling of patients who are to undergo
      cytoreductive resection of SMA gliomas.

PMID- 18813155
TI  - Image-guided craniotomy for cerebral metastases: techniques and outcomes.
AB  - OBJECTIVE: The purpose of the present study was to analyze the outcomes after
      craniotomies for brain metastases in a modern series using image-guided
      technologies either in the regular operating room or in the intraoperative
      magnetic resonance imaging unit. METHODS: Neurosurgical outcomes were analyzed
      for 49 patients who underwent 55 image-guided craniotomies for excision of brain
      metastases during a 5-year period. Tumors were located in critical and
      noncritical function regions of the brain. A total of 23 craniotomies for tumors
      in critical brain were performed using intravenous sedation anesthesia;
      craniotomies for noncritical function brain regions were completed under general
      anesthesia. The patients were also divided into Radiation Therapy Oncology Group
      recursive partitioning analysis (RPA) classes on the basis of age, Karnofsky
      Performance Scale scores, state of primary disease, and presence or absence of
      extracranial metastases. RESULTS: There was no perioperative mortality. Gross
      total resection, as verified by postoperative contrast-enhanced computed
      tomography or magnetic resonance imaging, was achieved in 96% of patients. The
      median anesthesia time was 4.25 hours, and the median length of hospital stay was
      3 days. In 51 symptomatic cases, there was complete resolution of symptoms in 70%
      (n = 36), improvement in 14% (n = 7), and no change in 12% (n = 6)
      postoperatively. No patient who was neurologically intact preoperatively
      deteriorated after surgery, and 93% of patients maintained or improved their
      functional status. Only two patients (3.6%) with significant preoperative
      deficits had increased long-term deficits postoperatively. The mean follow-up was
      1 year, and the local recurrence rate was 16%. The median survival of the entire
      group was 16.23 months (17.5 mo in RPA Class I, 22.9 mo in RPA Class II, and 9.8
      mo in RPA Class III). CONCLUSION: Gross total resection of brain metastases,
      including those involving critical function areas, can be safely achieved with a
      low morbidity rate using contemporary image-guided systems. RPA Class I and II
      patients with controlled primary disease benefit from aggressive treatment by
      surgery and radiation.

PMID- 18813156
TI  - Motor evoked potential monitoring with supratentorial surgery.
AB  - OBJECTIVE: To assess feasibility and clinical value of motor evoked potential
      (MEP) monitoring with surgery close to supratentorial motor areas and pathways.
      METHODS: Functional mapping by somatosensory evoked potential phase reversal and
      continuous MEP recording after high-frequency repetitive electrical cortex
      stimulation was performed during 182 operations in 177 patients. Significant MEP
      changes were reported to trigger surgical reaction. Intraoperative surgical and
      electrophysiological findings were documented prospectively. Patient files were
      reviewed for clinical data. MEP monitoring results were correlated with motor
      outcome. RESULTS: MEP recording was successful in 167 cases (91.8%). Inadequate
      electrode placement was an important reason for failed recording in the remaining
      patients, whereas preoperative paresis and anesthesia had no significant effect.
      Permanently disabling new motor deficit occurred in 8 cases (4.9%), whereas
      transient and nondisabling weakness was frequent (27.4%). Significant MEP changes
      occurred during 64 operations (39%). Irreversible MEP loss always predicted new,
      usually permanent, paresis. Unaltered MEP recordings indicated unimpaired motor
      function in the monitored muscle groups, except for rare transient deficit
      because of late edema and rebleeding. Irreversible MEP deterioration without loss
      and reversible changes could be associated with new paresis, which was transient
      in most patients. No major complications were observed, except for intraoperative
      generalized seizure in one epilepsy patient under insufficient anticonvulsant
      therapy. CONCLUSION: MEP monitoring with supratentorial surgery is feasible and
      safe. It may help to maximize resection within the limits of preserved motor
      function. Further evidence is needed to confirm these results.

PMID- 18813157
TI  - Intraoperative optical spectroscopy identifies infiltrating glioma margins with
      high sensitivity.
AB  - OBJECTIVE: Adult gliomas have indistinct borders. As the ratio of neoplastic
      cells to normal cells becomes lower, the ability to detect these cells
      diminishes. We describe a device designed to augment intraoperative
      identification of both solid tumor and infiltrating tumor margins. METHODS: A
      novel, intraoperative, optical spectroscopic tool, using both white light
      reflectance and 337-nm excitation fluorescence spectroscopy, is described.
      Discrimination algorithms have been developed to segregate neoplastic tissues
      from normal glial and neuronal elements. The spectroscopy device was used to
      measure 5 to 10 locations during glioma resection. Beneath the tool, a biopsy
      sample was obtained and the pathological results were reviewed in a blinded
      fashion. Samples were classified as solid tumor, infiltrating tumor, or normal
      gray or white matter. Comparisons were made between the optical spectra and the
      histopathological results of sampled areas in evaluating the sensitivity and
      specificity of the tool for tissue discrimination. RESULTS: Spectral data were
      obtained from 24 patients with glioma and from 11 patients with temporal lobe
      epilepsy. A sensitivity of 80% and a specificity of 89% in discriminating solid
      tumor from normal tissues were obtained. In addition, infiltrating tumor margins
      were distinguished from normal tissues with a sensitivity of 94% and a
      specificity of 93%. CONCLUSION: We have developed a handheld, optical
      spectroscopic device that may be used rapidly and in near real time with high
      sensitivity and reproducibility as an optical tissue discrimination tool in
      glioma surgery.

PMID- 18813158
TI  - Stimulation mapping via implanted grid electrodes prior to surgery for gliomas in
      highly eloquent cortex.
AB  - OBJECTIVE: To evaluate whether preoperative mapping of higher cortical functions
      with subdural grid electrodes can help to maximize resection in functional areas
      and avoid permanent injury. METHODS: A consecutive series of 16 patients (female:
      n = 7, male: n = 9, mean age of 38 yr) with a history of seizures and without
      focal deficit was reviewed, harboring gliomas located in the dominant hemisphere
      adjacent to or in the F3 gyrus/Broca area (n = 11), parietal/perisylvian area (n
      = 5) and additionally the pre- or postcentral area (n = 15). All patients in this
      series were operated for cytoreductive purposes only and not for treatment of
      intractable seizures. To preoperatively define and intraoperatively tailor the
      extent of resection all patients had a presurgical grid implantation for
      functional brain mapping. RESULTS: No permanent morbidity/mortality was observed
      after grid implantation and resective surgery. On postoperative MRI the resection
      was complete (100%), nearly complete (>90%) in n = 9 and subtotal (60% to <90%)
      in n = 5 cases. Twice, only biopsies were taken according to the results of
      mapping. All patients with high-grade gliomas had adjuvant treatment with
      radiation and chemotherapy. After a mean follow up of 20.4 months, no tumor
      relapse or growth was seen in all cases of resection. CONCLUSION: Preoperative
      grid mapping is a safe and precise instrument to evaluate language and/or
      associated left perisylvian functions in patients with gliomas. It may be
      considered a valid alternative to awake craniotomy to maximize safe resection.

PMID- 18813159
TI  - Implementation of fiber tract navigation.
AB  - OBJECTIVE: To implement fiber tracking in a common neuronavigation environment
      for routine clinical use to visualize major white matter tracts intraoperatively.
      METHODS: A single-shot, spin-echo diffusion weighted echo planar imaging sequence
      with six diffusion directions on a 1.5 T magnetic resonance scanner was used for
      diffusion tensor imaging. For three-dimensional (3-D) tractography, we applied a
      knowledge-based multiple volume of interest approach. Tracking was initiated in
      each voxel of the initial seed volume in retrograde and orthograde directions
      according to the direction of the major eigenvector by applying a tensor
      deflection algorithm. Tractography results were displayed as streamlines assigned
      direction encoding color. After selecting the fiber tract bundle of interest by
      defining inclusion and exclusion volumes, a 3-D object was generated
      automatically by wrapping the whole fiber tract bundle. This 3-D object was
      displayed along with other contours representing tumor outline and further
      functional data with the microscope heads-up display. RESULTS: In 16 patients
      (three cavernomas, 13 gliomas), major white matter tracts (pyramidal tract, n =
      14; optic radiation, n = 2) were visualized intraoperatively with a standard
      navigation system. Three patients developed a postoperative paresis, which
      resolved in two in the postoperative course. Additional planning time for
      tractography amounted to up to 10 minutes. Comparing the tractography results
      with a fiber bundle generated on a different platform by applying a distortion
      free sequence revealed a good congruency of the defined 3-D outlines in the area
      of interest. CONCLUSION: Fiber tract data can be reliably integrated into a
      standard neuronavigation system, allowing for intraoperative visualization and
      localization of major white matter tracts such as the pyramidal tract or optic
      radiation.

PMID- 18813160
TI  - Surgery of intrinsic cerebral tumors.
AB  - Tumors and other structural lesions located with and adjacent to the cerebral
      cortex present certain challenges in terms of the overall management and design
      of surgical strategies. This comprehensive analysis attempts to define the
      current understanding of cerebral localization and function and includes the
      latest advances in functional imaging, as well as surgical technique, including
      localization of tumors and neurophysiological mapping to maximize extent of
      resection while minimizing morbidity. Finally, it remains to be seen whether or
      not stimulation mapping will be the most useful way to identify function within
      the cortex in the future. Another potential paradigm would be to actually record
      baseline oscillatory rhythms within the cortex and, following presentation of a
      given task, determine if those rhythms are disturbed enough to identify eloquent
      cortex as a means of functional localization. This would be a paradigm shift away
      from stimulation mapping, which currently deactivates the cortex, as opposed to
      identifying an activation function which identifies functional cortex.

PMID- 18813161
TI  - Surgery of the human cerebrum. Trauma. Selected bibliography.

PMID- 18813162
TI  - Pure subdural hematomas: a postmortem analysis of their form and bleeding points.
AB  - OBJECTIVE: Although the literature concerning subdural hematomas (SDHs) is vast,
      few data are available as to the sources and related clinical differences of
      SDHs. Pure SDHs of arterial versus venous origin should be compared in terms of
      cause, size, space-occupying effect, and form. METHODS: We analyzed data from 46
      patients who died as a result of pure SDHs. Twenty-three SDHs resulted from
      bridging vein ruptures and 23 from torn cortical arteries. We performed a
      morphometric analysis of the intracranial situation on the horizontal plane at
      the level of the greatest fronto-occipital diameter. We included in our analysis
      the clinical one-dimensional parameters (e.g., hematoma thickness, midline
      shift); the areas of the hemispheres, the SDHs, and their displacement; and the
      hematoma volume. RESULTS: Most of the investigated postmortem characteristics of
      both types of hematomas were similar, with the exception of the form and the
      midline shift. SDHs resulting from arterial ruptures (which are generally located
      in the temporoparietal region) differ in form from those caused by bridging vein
      ruptures (which typically rupture in the frontoparietal parasagittal region).
      CONCLUSION: The form difference allows the probable rupture site to be estimated;
      this observation might prove useful for clinical purposes.

PMID- 18813163
TI  - Optimal temperature for the management of severe traumatic brain injury: effect
      of hypothermia on intracranial pressure, systemic and intracranial hemodynamics,
      and metabolism.
AB  - OBJECTIVE: We studied the effect of hypothermia on intracranial pressure,
      systemic and intracranial hemodynamics, and metabolism in patients with severe
      traumatic brain injury to clarify the optimal temperature for hypothermia, with a
      view toward establishing the proper management techniques for such patients.
      METHODS: The study was performed in 31 patients with severe head injury (Glasgow
      Coma Scale score as high as 5). All patients were sedated, paralyzed, ventilated,
      and cooled to 33 degrees C. Brain temperature, core temperature, intracranial
      pressure, cerebral perfusion pressure, jugular venous oxygen saturation, mixed
      venous oxygen saturation, cardiac output, oxygen delivery, oxygen consumption,
      and resting energy expenditure were monitored continuously. RESULTS: Intracranial
      pressure decreased significantly at brain temperatures below 37 degrees C and
      decreased more sharply at temperatures 35 to 36 degrees C, but no differences
      were observed at temperatures below 35 degrees C. Cerebral perfusion pressure
      peaked at 35.0 to 35.9 degrees C and decreased with further decreases in
      temperature. Jugular venous oxygen saturation and mixed venous oxygen saturation
      remained in the normal range during hypothermia. Resting energy expenditure and
      cardiac output decreased progressively with hypothermia. Oxygen delivery and
      oxygen consumption decreased to abnormally low levels at rectal temperatures
      below 35 degrees C, and the correlation between them became less significant at
      less than 35 degrees C than that when temperatures were 35 degrees C or higher.
      Brain temperature was consistently higher than rectal temperature by 0.5 +/- 0.3
      degrees C. CONCLUSION: These results suggest that, after traumatic brain injury,
      decreasing body temperature to 35 to 35.5 degrees C can reduce intracranial
      hypertension while maintaining sufficient cerebral perfusion pressure without
      cardiac dysfunction or oxygen debt. Thus, 35 to 35.5 degrees C seems to be the
      optimal temperature at which to treat patients with severe traumatic brain
      injury.

PMID- 18813164
TI  - Evolution of brain tissue injury after evacuation of acute traumatic subdural
      hematomas.
AB  - OBJECTIVE: Acute traumatic subdural hematoma complicated by brain parenchymal
      injury is associated with a 60 to 90% mortality rate. Early surgical evacuation
      of the mass lesion is essential for a favorable outcome, but the severity of the
      underlying brain injury determines the outcome, even when surgery has been
      prompt. The purpose of this study was to analyze tissue biochemical patterns in
      the brain underlying an evacuated acute subdural hematoma to identify a
      characteristic pattern of changes that might indicate evolving brain injury.
      METHODS: Prospectively collected data from 33 patients after surgical evacuation
      of acute subdural hematoma were analyzed. Both a brain tissue oxygen tension
      probe and an intracerebral microdialysis probe were placed in brain tissue
      exposed at surgery. On the basis of the postoperative clinical course, the
      patients were divided into three groups: patients with early intractable
      intracranial hypertension, patients with evolution of delayed traumatic injury
      (DTI), and patients with an uncomplicated course (the no-DTI group). RESULTS: The
      overall mortality rate was 46%, with 100% mortality in the intracranial
      hypertension group (five patients). Mortality in the DTI group was 53% compared
      with only 9% in the no-DTI group (P = 0.002). There were no significant
      differences in the initial computed tomographic scan characteristics, such as
      thickness of the subdural hematoma or amount of midline shift, among the three
      groups. Physiological variables, as well as the microdialysate measures of brain
      biochemistry, were markedly different in the intracranial hypertension group
      compared with the other groups. Differences between the other two groups were
      more subtle but were significant. Significantly lower values of brain tissue
      oxygen tension (14 +/- 8 mm Hg versus 27 +/- 14 mm Hg) and higher dialysate
      values of lactate and pyruvate were documented in patients who developed a
      delayed injury compared with patients with uncomplicated courses (4.1 +/- 2.3
      mmol/L versus 1.7 +/- 0.7 mmol/L for lactate, and 104 +/- 47 micromol/L versus 73
      +/- 54 micromol/L for pyruvate at 24 h after injury). CONCLUSION: Evolution of
      DTI in the area of brain underlying an evacuated subdural hematoma is associated
      with a significant increase in mortality. Postoperatively decreasing brain tissue
      oxygen tension and increasing dialysate concentrations of lactate and pyruvate in
      this area may warn of evolving brain injury and evoke further diagnostic and
      therapeutic activity.

PMID- 18813165
TI  - Penetrating civilian craniocerebral gunshot wounds: a protocol of delayed
      surgery.
AB  - OBJECTIVE: Several factors have led to our unique approach of delayed definitive
      debridement. We wanted to evaluate the effectiveness of our management and
      compare it with the existing data in the literature. METHODS: We retrospectively
      reviewed the records of 194 patients presenting between January 1996 and October
      2003 with penetrating craniocerebral gunshot wounds. After exclusion criteria,
      125 patients qualified. RESULTS: Of the patients, 88.8% were male. The mean age
      was 24.9 +/- 10.9 years. In 70.4% of patients, the presenting Glasgow Coma Scale
      (GCS) score was 3 to 8. Only 38 (30.4%) of the 125 patients survived, with poor
      outcome in 2 and good outcome in 36. Bilaterally fixed and dilated pupils and
      bihemispheric tract on computed tomographic scan were significantly related to
      poor outcome. There were 49 surgical procedures performed on 27 of the patients,
      with a mortality rate of 7.4%. Of the 38 survivors, 13 underwent no surgery.
      Average time to surgery was 11.04 days. Total rate of infection was 8%, and it
      did not influence outcome. No patient presenting with a GCS score of 3 or 4
      survived. Seventeen patients attended follow-up, for a total of 3609 days
      (average, 212 d) and very few late complications. CONCLUSION: Our supportive care
      of patients is not optimal. We should have saved more of our patients who
      presented with GCS scores of 14 and 15 who subsequently died. We have been able
      to report unconventionally late surgical management of two-thirds of survivors,
      with no surgery in one-third of survivors. Despite a high rate of infectious
      complications, infection did not lead to death or disability. Our protocol rarely
      leads to patients surviving in a permanently vegetative state. In the future, we
      would perform early surgery for patients who present awake and continue our
      current management for poor-grade patients. In this way, we will improve the
      number of good outcomes without increasing the population of severely damaged and
      dependent survivors.

PMID- 18813166
TI  - The management of patients with intradural post-traumatic mass lesions: a
      multicenter survey of current approaches to surgical management in 729 patients
      coordinated by the European Brain Injury Consortium.
AB  - OBJECTIVE: Controversy exists about the indications and timing for surgery in
      head injured patients with an intradural mass lesion. The aim of this study was
      to survey contemporary approaches to the treatment of head injured patients with
      an intradural lesion, placing a particular focus on the utilization of
      decompressive craniectomy. METHODS: A prospective international survey was
      conducted over a 3-month period in 67 centers from 24 countries on the
      neurosurgical management of head injured patients with an intradural mass lesion
      and/or radiological signs of raised intracranial pressure. Information was
      obtained about demographic, clinical, and radiological features; surgical
      management, and mortality at discharge. RESULTS: Over the period of the study,
      data were collected about 729 patients consecutively admitted to one of the
      participating centers. The survey included 397 patients with a severe head injury
      (Glasgow Coma Scale [GCS] 3-8), 155 with a moderate head injury (GCS 9-12) and
      143 patients with a mild head injury (GCS 13-15). An operation was performed on
      502 patients (69%). Emergency surgery (<24 h) was most frequently performed for
      patients with an extracerebral mass lesions (subdural hematomas) whereas delayed
      surgery was most frequently performed for an intracerebral hematoma or contusion.
      Decompressive craniectomy was performed in a substantial number of patients,
      either during an emergency procedure (n = 134, 33%) or a delayed procedure (n =
      47, 31%). The decompressive procedure was nearly always combined with evacuation
      of a mass lesion. The size of the decompression was however considered too small
      in 25% of cases. CONCLUSION: The results provide a contemporary picture of
      neurosurgical surgical approaches to the management of head injured patients with
      an intradural mass lesion and/or signs of raised intracranial pressure in some
      Neurosurgical Units across the world. The relative benefits of early versus
      delayed surgery in patients with intraparenchymal lesions and on the indications,
      technique and benefits of decompressive craniectomy could be topics for future
      head injury research.

PMID- 18813167
TI  - Acute traumatic intraparenchymal hemorrhage: risk factors for progression in the
      early post-injury period.
AB  - OBJECTIVE: To characterize the natural course of traumatic intraparenchymal
      contusions and hematomas (IPHs) and to identify risk factors for IPH progression
      in the acute post-injury period. METHODS: A retrospective analysis was performed
      on a prospective observational database containing 113 head trauma patients
      exhibiting 229 initially nonoperated acute IPHs. The main outcome variable was
      radiographic evidence of IPH progression on serially obtained head computed
      tomographic (CT) scans. Secondary outcomes included the actual amount of IPH
      growth and later surgical evacuation. Univariate and multivariate analyses (using
      a generalized estimate equation) were applied to both demographic and initial
      radiographic features to identify risk factors for IPH progression and surgery.
      RESULTS: Overall, 10 IPHs (4%) shrank, 133 (58%) remained unchanged, and 86 (38%)
      grew between the first and second head CT scan. IPH progression was independently
      associated with the presence of subarachnoid hemorrhage (odds ratio [OR], 1.6;
      95% confidence interval [CI], 1.12-2.3), presence of a subdural hematoma (OR,
      1.94; 95% CI, 1.1-3.43), and initial size (OR, 1.11; 95% CI, 1.02-1.21, for each
      cm volume). Size of initial IPH proportionately correlated with the amount of
      subsequent growth (linear regression, P < 0.001). Worsened Glasgow Coma Score
      between initial and follow-up head CT scan (OR, 8.6; 95% CI, 1.5-50), IPH growth
      greater than 5 cm (OR, 7.3; 95% CI, 1.6-34), and effacement of basal cisterns on
      initial CT scan (OR, 9.0; 95% CI, 1.5-52) were strongly associated with late
      surgical evacuation. CONCLUSION: A large proportion of IPHs progress in the acute
      post-injury period. IPHs associated with subarachnoid hemorrhage, a subdural
      hematoma, or large initial size should be monitored carefully for progression
      with repeat head CT imaging. Effacement of cisterns on the initial head CT scan
      was strongly predictive of failure of nonoperative management, thereby leading to
      surgical evacuation. These findings should be important factors in the
      understanding and management of IPH.

PMID- 18813168
TI  - Surgery of cerebral trauma and associated critical care.
AB  - The last 30 years have been both exciting and frustrating for those in the field
      of traumatic brain injury (TBI). Much has been learned, but no new treatment has
      been shown to improve patient outcomes despite the execution of many clinical
      trials. The overall incidence of TBI has decreased, probably because of intensive
      efforts toward prevention and education. Rigorous assessment of available
      research has produced several evidence-based guidelines for the management of
      neurotrauma patients. The creation of organized emergency medical services
      systems in many regions has improved prehospital care. Computed tomographic scans
      have become the gold standard for obtaining immediate images of patients with
      TBI, and ongoing advances in visualizing cerebral metabolism continue to be
      remarkable. The major current question regarding surgical treatment for TBI
      involves the role of decompressive craniectomy, an operation that first fell out
      of favor and has since (in the last three decades) enjoyed a resurgence of
      interest. Growing interest in the intensive care management of TBI patients
      helped to establish the new field of neurocritical care. Prophylactic
      hyperventilation is no longer recommended, and earlier recommendations for
      aggressive elevation of blood pressure have been softened to endorsement of a
      cerebral perfusion pressure of 60 mmHg. Recombinant factor VIIa is increasingly
      used for minimizing complications related to coagulopathy. Intracranial pressure
      monitoring is now recommended for the majority of TBI patients. At present,
      available technologies allow measurement of other aspects of cerebral metabolism
      including cerebral blood flow, brain oxygen tension, biochemistry, and electrical
      activity. Therapeutic interventions that are growing in popularity or are
      presently under investigation include administration of hypertonic saline,
      hyperoxygenation, decompressive craniectomy, and hypothermia. Rehabilitation has
      become accepted as an important part of the TBI recovery process, and additional
      work is needed to identify optimal interventions in this area. Socioeconomic
      factors will play a growing role in our treatment of TBI patients. Although much
      progress has been made in the last 30 years, the challenge now is to find ways to
      translate that progress into improved care and outcomes for TBI patients.

PMID- 18813169
TI  - Surgery of the human cerebrum. Imaging. Selected bibliography.

PMID- 18813170
TI  - Cerebral arteriovenous malformations: comparison of novel magnetic resonance
      angiographic techniques and conventional catheter angiography.
AB  - OBJECTIVE: To investigate the potential of novel magnetic resonance (MR)
      angiographic techniques for the assessment of cerebral arteriovenous
      malformations. METHODS: Forty patients who were about to undergo stereotactic
      radiosurgery were prospectively recruited. Three-dimensional, sliding-slab
      interleaved ky (SLINKY), time-of-flight acquisition was performed, as was a
      dynamic MR digital subtraction angiography (DSA) procedure in which single thick
      slices (6-10 cm) were obtained using a radiofrequency spoiled Fourier-acquired
      steady-state sequence (1 image/s). Sixty images were acquired, in two or three
      projections, during passage of a 6- to 10-ml bolus of gadolinium chelate.
      Subtraction and postprocessing were performed, and images were viewed in an
      inverted cine mode. SLINKY time-of-flight acquisition was repeated after the
      administration of gadolinium. Routine stereotactic conventional catheter
      angiography was performed after MR imaging. All images were assessed (in a
      blinded randomized manner) for Spetzler-Martin grading and determination of
      associated vascular pathological features. RESULTS: Forty-one arteriovenous
      malformations were assessed in 40 patients. Contrast-enhanced (CE) SLINKY MR
      angiography was the most consistent MR imaging technique, yielding a 95%
      correlation with the Spetzler-Martin classification defined by conventional
      catheter angiography; MR DSA exhibited 90% agreement, and SLINKY MR angiography
      exhibited 81% agreement. CE SLINKY MR angiography provided improved nidus
      delineation, compared with non-CE SLINKY MR angiography. Dynamic information from
      MR DSA significantly improved the observation of early-draining veins and
      associated aneurysms. CONCLUSION: CE SLINKY MR angiographic assessment of
      cerebral arteriovenous malformations offers significant advantages, compared with
      the use of non-CE SLINKY MR angiography, including improved nidus demonstration.
      MR DSA shows promise as a noninvasive method for dynamic angiography but is
      presently restricted by limitations in both temporal and spatial resolution.

PMID- 18813171
TI  - Preoperative and intraoperative diffusion tensor imaging-based fiber tracking in
      glioma surgery.
AB  - OBJECTIVE: To investigate the intraoperative displacement of major white matter
      tracts during glioma resection by comparing preoperative and intraoperative
      diffusion tensor imaging-based fiber tracking. METHODS: In 37 patients undergoing
      glioma surgery, preoperative and intraoperative diffusion tensor imaging was
      performed with a 1.5-T magnetic resonance scanner applying an echo-planar imaging
      sequence with six diffusion directions. For three-dimensional tractography, we
      implemented a knowledge-based multiple-region-of-interest approach applying user
      defined seed regions in the color-coded maps of fractional anisotropy. Tracking
      was initiated in both the retrograde and orthograde directions according to the
      direction of the principal eigenvector in each voxel of the region of interest.
      The tractography results were also assigned color, applying the convention used
      in color-coded fractional anisotropy maps. RESULTS: Preoperative and
      intraoperative fiber tracking was technically feasible in all patients. Fiber
      tract visualization gave a quick and intuitive overview of the displaced course
      of white matter tracts in three-dimensional space. Comparison of preoperative and
      intraoperative tractography depicted a marked shifting of major white matter
      tracts during glioma removal. Maximum white matter tract shifting ranged from -8
      to +15 mm (+2.7 +/- 6.0 mm; mean +/- standard deviation); in 29.7%, an inward and
      in 62.2%, an outward shifting was detected. CONCLUSION: Comparing preoperative
      and intraoperative fiber tracking visualizes a marked shifting and deformation of
      major white matter tracts because of tumor removal. This shifting emphasizes the
      need for an intraoperative update of navigation systems during resection of deep
      seated tumor portions near eloquent brain areas. Fiber tracking is a method not
      only for preoperative neurosurgical visualization but also for further
      intraoperative planning.

PMID- 18813172
TI  - Functional identification of the primary motor area by corticospinal
      tractography.
AB  - OBJECTIVE: For quick and stable identification of the primary motor area (PMA),
      diffusion tensor imaging (DTI) data were acquired and corticospinal tractography
      was mathematically visualized. METHODS: Data sets of DTI, anatomic magnetic
      resonance imaging, and functional magnetic resonance imaging with finger-tapping
      tasks were acquired during the same investigation in 30 patients with a brain
      lesion affecting the motor system. Off-line processing of DTI data was performed
      to visualize the corticospinal tract, placing a seed area in the cerebral
      peduncle of the midbrain, where the corticospinal tract is densely concentrated.
      Somatosensory evoked magnetic fields and intraoperative cortical somatosensory
      evoked potentials were recorded with electrical stimulation of the median nerve
      to confirm the results of the corticospinal tractography. RESULTS: Functional
      magnetic resonance imaging and somatosensory evoked magnetic fields failed to
      identify the PMA in eight patients (16.7%) and one patient (3.8%) investigated,
      respectively, because of cortical dysfunctions caused by brain lesions. DTI data
      were acquired within 3 minutes without patient tasks. Using the appropriate seed
      area and fractional anisotropy, corticospinal tractography successfully indicated
      the PMA location in all patients. The suspected PMA and central sulcus locations
      were confirmed by the cortical somatosensory evoked potentials. CONCLUSION:
      Corticospinal tractography enables identification of the PMA and is beneficial,
      particularly for patients who present with dysfunction of the PMA.

PMID- 18813173
TI  - Magnetoencephalography in neurosurgery.
AB  - OBJECTIVE: To present applications of magnetoencephalography (MEG) in studies of
      neurosurgical patients. METHODS: MEG maps magnetic fields generated by electric
      currents in the brain, and allows the localization of brain areas producing
      evoked sensory responses and spontaneous electromagnetic activity. The identified
      sources can be integrated with other imaging modalities, e.g., with magnetic
      resonance imaging scans of individual patients with brain tumors or intractable
      epilepsy, or with other types of brain imaging data. RESULTS: MEG measurements
      using modern whole-scalp instruments assist in tailoring individual therapies for
      neurosurgical patients by producing maps of functionally irretrievable cortical
      areas and by identifying cortical sources of interictal and ictal epileptiform
      activity. The excellent time resolution of MEG enables tracking of complex
      spaciotemporal source patterns, helping, for example, with the separation of the
      epileptic pacemaker from propagated activity. The combination of noninvasive
      mapping of subcortical pathways by magnetic resonance imaging diffusion tensor
      imaging with MEG source localization will, in the near future, provide even more
      accurate navigational tools for preoperative planning. Other possible future
      applications of MEG include the noninvasive estimation of language lateralization
      and the follow-up of brain plasticity elicited by central or peripheral neural
      lesions or during the treatment of chronic pain. CONCLUSION: MEG is a mature
      technique suitable for producing preoperative "road maps" of eloquent cortical
      areas and for localizing epileptiform activity.

PMID- 18813174
TI  - Imaging of the cerebrum.
AB  - The history of the development of cerebral imaging is a complex combination of
      the forces of innovation at both the individual and industrial levels. Principal
      paradigms of neuroimaging shifted as a result of technological breakthroughs,
      beginning with the discovery of x-rays and continuing with the development of
      computerized imaging to the latest imaging paradigm, nuclear magnetic resonance
      imaging. We discuss these landmarks in neuroimaging in historical context, with
      emphasis on the particularly rapid development of imaging technology during the
      past 30 to 40 years, including the most recent emerging technologies.

PMID- 18813175
TI  - The cerebrum. Anatomy.
AB  - The cerebrum is the crown jewel of creation and evolution. It is a remarkably
      delicate, intricate, and beautiful structure. The goal of this chapter is to
      provide the information needed to permit the neurosurgeon to navigate accurately,
      gently, and safely around and through the cerebrum and intracranial space. The
      location of deep structures is frequently described in relation to cranial and
      superficial cerebral landmarks in order to develop the concept of see-through, x
      ray type knowledge of the cerebrum. In numerous illustrations, stepwise
      dissections are used to clarify the relationship between structures in different
      layers. Important clinical and surgical concepts are intermixed with the
      description of the cerebrum and its arteries, veins, and ventricles.

PMID- 18813176
TI  - Surgery of the human cerebrum. History. Selected bibliography.

PMID- 18813177
TI  - Surgery of the human cerebrum--a collective modernity.
AB  - Safe and beneficial surgery of the human cerebrum is arguably one of mankind's
      most notable achievements and one of the great testimonials to human creativity,
      intelligence, and character. In many ways, it is a testimony to the climates of
      civilization that have marked human history. In historical terms, in the year
      2007, cranial surgery celebrated its 12,000th birthday, with cranial manipulation
      for various religious, mystical, and therapeutic reasons being evident in Africa
      more than 10 millennia before the birth of Christ. This article traces the major
      developments and attitudes that have laid the foundations of modernity in what is
      currently surgery and medicine's most exciting and complex technical exercise. It
      is in fact a 12,000 year prelude to the modernity that we currently enjoy. Before
      attempting to define our modernity and emerging futurism with reinvention,
      examination of the prolonged and tedious invention is appropriate for
      perspective. The following examines and recounts the accrual of data and changes
      in attitude over the stream of history that have allowed refined surgery of the
      human cerebrum to become a reality.

PMID- 18813178
TI  - The human cerebrum and the reinvention of neurosurgery.

PMID- 18813179
TI  - Admission glycemia and markers of inflammation are independent outcome predictors
      in primary PCI in non-diabetic patients.
AB  - AIM: To assess the prognostic value of admission plasma glucose (APG) respect to
      clinical variables and inflammatory markers in a selected population of non
      diabetic patients with ST elevation myocardial infarction (STEMI) treated with
      primary angioplasty (primary coronary intervention, PCI). METHODS: A total of 188
      consecutive non-diabetic STEMI patients undergoing primary PCI were divided into
      four quartiles based on APG (<117, 117-140, 141-170, >170 mg/dL). Combined end
      point of major adverse cardiac events (MACE) was defined as death, acute heart
      failure, re-infarction, unstable angina or inducible ischemia. RESULTS: Event
      free survival from MACE was significantly (P<0.001) correlated with APG quartiles
      and decrease from the lowest to the highest: 6 months event-free survival was
      89.3%, 77.4%, 59.1%, 42.5%. Patients with higher APG were characterized by a
      significantly higher Killip class (P<0.001), higher serum creatinine (P<0.05) on
      admission, and a lower rate of thrombolysis in myocardial infarction (TIMI) 3
      flow after PCI (P<0.05). Multivariate analysis showed APG>170 mg/dL (hazard ratio
      [HR] 2.39, 95% confidence interval [CI] 1.24 to 4.65, P<0.01), admission high
      sensitivity C-reactive protein level (HR 1.19, 95% CI 1.07 to 1.31, P<0.001),
      white blood cells count (HR 1.07, 95% CI 1.00 to 1.14, P<0.04) and heart rate (HR
      1.02, 95% CI 1.00 to 1.04, P<0.02) to be independent predictors of MACE.
      CONCLUSION: Admission glycemia and inflammatory markers are independent
      predictors of MACE in the mid-term follow-up in non-diabetic STEMI treated with
      primary PCI. Further investigations are needed to study the pathogenesis of
      stress hyperglycaemia, interactions with mechanisms of inflammation and whether
      early and aggressive treatment with insulin may influence outcome of primary PCI.

PMID- 18813180
TI  - Meta-analysis of 5-year outcomes of CABG vs PCI with stenting in patients with
      multivessel disease.
AB  - AIM: The purpose of this meta-analysis was to systematically review and
      synthesize existing data on long term outcomes of coronary artery bypass grafting
      (CABG) and percutaneous coronary intervention (PCI) with multiple stenting in
      patients with multivessel coronary artery disease. METHODS: Three randomized
      control trials of CABG versus stenting with a 5-year follow-up and a total number
      of 2 063 patients were included in the meta-analysis. The primary end-point of
      the study was freedom from major adverse cardiovascular events at 5 years.
      RESULTS: After 5 years of follow-up, 42.81% of patients randomized to PCI with
      stenting versus 20.81% of patients randomized to CABG reached the primary
      clinical end-point(relative risk [RR] 2.16, 95% confidence interval [CI] 1.38
      3.38). Repeat revascularization procedures occurred more frequently in patients
      allocated to PCI with multiple stenting compared with CABG (30.29% versus 7.45%,
      RR 4.47 and 95% CI 2.75-7.29). Non fatal myocardial infarction (MI) (6.6% versus
      6.2%, RR 1.00 and 95% CI 0.58-1.70) was nearly equal in the two groups while
      deaths (9.3% versus 7.4%, RR 1.50 and 95% CI 0.61-3.66) were slightly higher in
      patients treated by PCI as compared to CABG. CONCLUSION: Five years after the
      initial procedure, there is no survival benefit for CABG over PCI, but major
      adverse cardiovascular events and repeat revascularization procedures are high
      after PCI.

PMID- 18813181
TI  - Early post-procedural migraine attack predicts migraine resolution after patent
      foramen ovale transcatheter closure.
AB  - AIM: In patients with patent foramen ovale-related migraine, the procedure of
      transcatheter closure itself is likely to cause a migraine attack. Our study is
      aimed to evaluate the incidence of migraine attacks immediately after closure
      procedure and their clinical and potential prognostic significance. METHODS: We
      reviewed our database from January 2005 to April 2007 searching for patients with
      severe disabling migraine despite anti-headache therapy who were submitted to
      transcatheter closure of patent foramen ovale (PFO). Medical records of these
      patients were carefully reviewed in order to record migraine episodes immediately
      (0 to 6 h) after closure procedure. RESULTS: Twenty-one patients with previous
      stroke and migraine underwent PFO closure: the procedure was successful in all of
      the patients with no perioperative and in-hospital complications. Ten patients
      (47.6%) experienced a migraine attack of mean duration 3.5+/-2.4 h immediately
      after the closure procedure. Those patients had the same procedure time compared
      with other patients, but had larger PFO: patients with migraine attack
      immediately after closure had higher rate of complete abolition of migraine in
      the follow-up. CONCLUSION: Although more larger studies are needed to evaluate
      the exact relationships between migraine and PFO, in patients with a tight
      correlation between migraine and PFO, a prolonged opening of the PFO, as during
      closure procedure, may cause a migraine attack immediately after the closure.
      This fact can be considered a positive prognostic factor for migraine abolishment
      in the follow-up.

PMID- 18813182
TI  - The combined effect of calcium channel blocker Lercanidipine and antioxidants on
      low-grade systemic inflammation parameters in essential hypertension patients.
AB  - AIM: The influence of oxidative stress (OS) and inflammation on up-regulation of
      blood pressure (BP) has been well established. Peripheral polymorphonuclear
      leukocytes (PMNLs) are primed in essential hypertension (EH) patients, releasing
      uncontrolled superoxide anion contributing to OS in these patients. PMNL priming
      correlates with PMNL intracellular calcium [Ca2+]i. Previous studies have shown
      that treatment by calcium channel blockers lowers BP, OS and inflammation. In the
      same time, there are some trials showing down regulation influence of ''anti
      oxidative'' drugs as Vitamin E and C to inflammation and OS. The data of clinical
      significance of anti-oxidative drugs to BP is controversial. The aim of this
      paper was to evaluate the benefit of combined treatment by calcium channel
      blockers (Lercanidipine) and antioxidative drugs (Vitamins C and E) on BP and on
      parameters of inflammation and OS. METHODS: Sixteen new diagnosed patients with
      mild to moderate BP were sampled to 2 groups after randomization by age, sex, and
      mean arterial pressure (MAP), cholesterol and glucose level. The first group was
      treated by Lercanidip-ine only, the second group by combination of Lercanidipine
      and antioxidative drugs both for 6 months. PMNL priming was assessed by the rate
      of superoxide release from separated, phorbol ester-stimulated PMNLs and by PMNL
      CD11b level. Inflammation was reflected by plasma C-reactive protein (CRP) and
      albumin levels, white blood cells (WBC) and PMNL counts and by PMNL apoptosis.
      RESULTS: In both groups, BP decreased after 6 months of treatment, and in a more
      pronounced manner following the combined treatment. In both groups PMNL priming
      parameters remained unchanged after 6 months of treatment, with transient
      differences between the two groups during the experimental period. In both groups
      inflammation parameters remained unchanged after 6 months of treatment, without
      difference between the two groups, except a pronounced decrease in the percentage
      of apoptotic PMNLs in the combined treatment group. CONCLUSION: Our trial shows a
      clinical benefit combining calcium channel blockers treatment with antioxidants
      in BP treatment, although it did not reveal significant influence of
      complementation of antioxidants to calcium channel blockers on OS and
      inflammation parameters. Additional clinical and laboratory investigations are
      needed to clear this issue. Conflicting data are reported on the influence of
      vitamins E and C on OS and inflammation together with controversy regarding anti
      oxidative drugs and their effect on BP.

PMID- 18813183
TI  - The effect of conversion type on P wave dispersion in patients with atrial
      fibrillation.
AB  - AIM: The aim of this study was to investigate whether conversion type of atrial
      fibrillation (AF) to sinus rhythm affects the P wave dispersion (PD) in patients
      with AF. METHODS: Based on conversion type, 95 consecutive patients with AF<3
      months were divided into 3 groups: spontaneous cardioversion (SC) (N.=33, mean
      age: 60.6+/-11.6 years), pharmacologic cardioversion (PC) (N.=32, mean age:
      59.2+/-9.6 years) and electrical cardioversion (EC) (N.= 30, mean age: 65.3+/
      10.6 years). P wave duration (maximum and minimum) were measured in 12-lead ECG,
      and PD was calculated. RESULTS: Left atrial diameter and AF duration were
      significantly higher in EC (43.6+/-4.8 mm and 794.1+/-815.1 h) than SC (38.5+/
      3.9 mm and 13.8+/-18.3 h) and PC (40.9+/-4.5 mm and 65.3+/-148.5 h) groups
      (P<0.01). P maximum was much longer in EC group compared with SC and PC group
      (121.6+/-9.7, 108.4+/-6.4 and 115.8+/-8.6 ms, P=0.01, respectively). There was a
      significant difference in PD among SC, PC and EC groups (44.4+/-9.2, 49.5+/-8.7
      and 53.5+/-8.8 ms; P=0.005, respectively). PD correlated with AF duration
      (r=0.36, P=0.03), left atrial diameter (r=0.45, P=0.002) and conversion type
      (r=0.29, P=0.03). However, there was no significant association between PD and
      conversion type in multivariate analysis. The prolonged PD resulted from AF
      duration (P=0.01) and the left atrial size P=0.001). CONCLUSION: This study
      suggests that conversion type of AF to sinus rhythm has no effect on P wave
      duration and independent of AF duration and the left atrial diameter.

PMID- 18813184
TI  - Bioabsorbable and biocompatible stents. Is a new revolution coming?
AB  - With the introduction of drug-eluting stents (DES) the problem of restenosis
      after percutaneous stent implantation was partially resolved. In the first
      generation of DES a stainless steel platform was coated with a durable polymer
      eluting and controlling the release of an active restenotic drug. The impairment
      of re-endothelization after DES implantation, one of the causes of late stent
      thrombosis, was to some extent attributed to the properties of the durable
      polymer and/or drug that it eluted. The introduction of biodegradable platforms
      and biocompatible polymers may potentially address this issue. Modern
      technologies are being applied to improve the characteristics of biodegradable
      stents and find new active pharmacological agents or combinations of standard
      antirestenotic and antithrombotic drugs that can be eluted from the stents, in
      order to improve their safety profile and clinical utility.

PMID- 18813185
TI  - Multivessel percutaneous coronary intervention: a review of the literature and
      fallacies in its interpretation.
AB  - Since its inception in the 1960s, coronary revascularization has established
      itself as a fundamental therapy for treating the acute and chronic manifestations
      of atherosclerotic coronary disease. Catheter-based techniques were realized in
      the late 1970s and have evolved from balloon dilatation of simple, discrete
      stenoses to complex, multivessel interventions across the spectrum of coronary
      disease presentations. In retrospect, there were two defining technological
      developments the introduction of coronary stenting which enabled more stable
      acute outcomes and the evolution of drug-eluting stents which ameliorated the
      effect of neointimal hyperplasia the dominant cause of delayed loss of efficacy.
      The role of catheter-based intervention in multivessel disease is well
      established in the treatment of ST-elevation myocardial infarction and acute
      coronary syndromes. On the contrary, in the arena of in stable coronary disease,
      its utility is keenly debated. The pace of development in cardiovascular
      pharmacology has rendered early investigation of best treatment strategies
      largely obsolete, while newer revascularization techniques have successfully
      extended the remit of catheter-based multivessel intervention strategies to
      include left main stem disease, bifurcation stenosis and chronic occlusions.
      Consequently complete revascularization is now available via a percutaneous
      approach and conventional beliefs relating to choice of revascularization
      strategy deserve re-assessment. The authors present a contemporary review of the
      literature and a challenge against fallacies in its interpretation.

PMID- 18813186
TI  - Optical coherence tomography: clinical applications and the evaluation of DES.
AB  - Optical coherencet tomography (OCT) is a light-based imaging modality that can
      provide in vivo high-resolution images of the coronary artery. In the last years
      there has been a continuous technical development that has improved the image
      quality and has simplified the acquisition procedure in order to spread the
      clinical applicability of this technique. Due to its high resolution OCT, can be
      a very valuable tool for the evaluation of the coronary vessel wall, the acute
      and long-term impact of catheter-based intervention on plaque structure and
      vessel architecture and the assessment of stents. During stenting, OCT offers the
      possibility to evaluate stent apposition in great detail and can identify the
      presence of vessel injury due to stent implantation. At follow-up, the tissue
      coverage of individual struts can be imaged with OCT. This is of increasing
      interest in drug-eluting stents in which the neointimal proliferation is
      inhibited to such extent that it might not be visualized with conventional
      intracoronary imaging techniques such as IVUS. Regarding the analysis of the
      coronary vessel wall, OCT holds promise for the identification of thin cap
      fibroatheroma due to its ability to provide information about plaque composition,
      presence of macrophages and thickness of the fibrous cap.

PMID- 18813187
TI  - The management of chronic total coronary occlusions.
AB  - Although recent consensus has clearly defined chronic total occlusions (CTO),
      attempted percutaneous coronary intervention (PCI) remains low.
      Histopathologically, CTOs are characterized by fibrous caps, varying degrees of
      plaques, and neovascularization, with both increasing with the age of the CTO.
      Multiple registries and studies show that successful PCI of CTOs can improve
      symptoms, left ventricular function, and mortality. There is overwhelming
      evidence that very low restenosis and reocclusion rates can be obtained with drug
      eluting stents after recanalization of CTOs. PCI should be considered the
      preferred initial revascularization modality in patients in whom a high
      procedural success rate may be anticipated. Novel techniques have greatly
      enhanced procedural success, and include ''parallel'' and ''seesaw'' wire
      techniques, balloon anchoring, subintimal tracking and reentry (STAR), retrograde
      approach, contralateral injection, and intravascular ultrasound (IVUS) guidance.
      Improvements in wire technology have largely been responsible for improved
      procedural success in PCI of CTO, while application of new technologies hold
      promise to significantly better outcomes. Magnetic resonance imaging (MRI) and
      multislice computed tomography (CT) are already employed in formulating treatment
      strategies and their role in the treatment of CTOs is likely to increase.

PMID- 18813188
TI  - Transcatheter heart valves for the treatment of aortic stenosis: state-of-the
      art.
AB  - Degenerative aortic stenosis is the most frequent heart valve disease. As an
      alternative to surgical aortic valve replacement, several companies are working
      on the development of new prosthesis designed to be deployed by transcatheter
      approaches. Both transfemoral and transapical techniques are feasible, and
      initial trials in high-risk patients show good procedural outcomes and mid-term
      (up to 2 years) functionality. Two first-generation prosthesis (Edwards-SAPIEN
      and CoreValve Revalving System) are commercially available in Europe, and a
      number of other second-generation valves (with the capabilities of repositioning
      and retrievability) are under evaluation. Among them, the Sadra-Lotus Valve, The
      Direct Flow Medical valve and the Paniagua Heart Valve have published first-in
      man results; the JenaValve and AorTx devices have also been temporarily implanted
      in humans. The development of repositionable and retrievable prosthesis with
      improved profile is mandatory, and it is the main focus of current projects. Not
      only technical improvements but also operators specialization and an optimal
      patient selection are essential to improve these initial RESULTS: Some procedural
      challenges need to be overcome prior to the expansion of these techniques to
      lower risk groups, and time is needed for detailed long-term outcomes and risk
      estimations. Only with a close collaboration among different specialists, basic
      researchers and the industry will the future development of transcatheter aortic
      implantation techniques be ensured.

PMID- 18813189
TI  - Exercise training in prevention and rehabilitation: which training mode is best?
AB  - Physical activity is a well-established means of reducing the risk and
      consequences of nearly all forms of cardiovascular disease. Several exercise
      training regimens have been utilized with varying degrees of success on selected
      outcomes, which was led to the question of which training regimen provides
      optimal benefits. Just as cardiovascular disease is not a single condition, but
      often a conglomerate of associated pathologies and comorbidities that combine to
      increase risk of cardiac mortality, no single exercise training program is
      optimal for risk reduction in all individuals or conditions. The mode, frequency
      and duration of training must be tailored to the individual, considering not only
      the present state of risk or disease, but also the individual's physical
      capabilities/limitations, personal goals and preferences for optimal benefits and
      long-term adherence. However, accumulating evidence indicates that some training
      modes may supplement or exceed the benefits conferred by traditional moderate
      intensity aerobic training alone. The purpose of this review is to provide an
      overview of clinical and epidemiological studies that have examined the benefits
      of various training regimens, focusing on the mode of training (aerobic, interval
      or resistance training), the intensity and volume of exercise, and various
      training modalities (e.g., walking, cycling, or aqua-aerobics), and briefly
      discuss considerations regarding patient safety and compliance. It is hoped that
      this review will familiarize clinicians with the current state of research in the
      field to facilitate a more informed and evidence-based approach to exercise
      prescription for individuals with and without cardiovascular disease.

PMID- 18813190
TI  - Abdominal aortic aneurysm associated with renal ectopia.
AB  - This report describes a rare case of concurrent abdominal aortic aneurysm and
      bilateral renal ectopia. Preoperative work-up included intravenous pyelography
      and angiography to assess renal function, renal artery anatomy, and ureter
      position. Conventional surgery was performed without renal protection. No
      deterioration in postoperative renal function was observed.

PMID- 18813191
TI  - Ventricular arrhythmias in children: the uselessness of MRI.

PMID- 18813192
TI  - Transcatheter device-closure of an unusual presumably post-traumatic tunnel-like
      ventricular septal defect.

PMID- 18813193
TI  - Apical hypertrophic cardiomyopathy: quickly non-invasive diagnosis by intravenous
      contrast echocardiography.

PMID- 18813194
TI  - New insights and gains in pancreatic cancer.

PMID- 18813195
TI  - Early detection of pancreatic cancer: why, who, and how to screen.
AB  - BACKGROUND: Pancreatic cancer represents the fourth-leading cause of cancer death
      in the United States, with a dismal 5-year survival rate of less than 5%. Despite
      advancements in screening and early detection of other cancers such as breast and
      colon cancer, no reliable screening test exists for pancreatic cancer.
      Subsequently, the majority of patients present with advanced-stage disease
      leading to a poor prognosis. Because of the relatively low incidence, current
      efforts are focused on early detection and screening only in patients at high
      risk for the development of the disease. METHODS: We discuss the practical
      considerations encountered when determining if an individual should be screened
      for pancreatic cancer. The current literature was reviewed regarding risk
      factors, genetic syndromes, screening modalities, and screening studies of
      pancreatic cancer. The current high-risk pancreatic screening program at our
      institute is also summarized. RESULTS: Current efforts to detect pancreatic
      cancer at a curative phase are focused on screening individuals at high risk for
      the development of this disease. They include kindreds with two or more first
      degree relatives affected with this disease and those with known hereditary
      pancreatic cancer syndromes. Hereditary pancreatic cancer syndromes include Peutz
      Jeghers syndrome, familial breast cancer syndrome, and familial atypical multiple
      mole melanoma syndrome. Of all the screening modalities available, endoscopic
      ultrasound is the most sensitive and specific screening tool to evaluate the
      pancreas and has been proven to detect early precancerous and cancerous changes
      in clinical studies. CONCLUSIONS: Early detection and screening for pancreatic
      cancer in the current state should be limited to high-risk patients, although
      hereditary/familial factors account for only 10% of patients with pancreatic
      cancer. Continued efforts are needed to discover effective test to identify
      patients with nonhereditary risk factors who will benefit from screening and also
      to develop less invasive and more cost-effective screening modalities aimed at
      controlling pancreatic cancer.

PMID- 18813196
TI  - Outcomes following resection of pancreatic adenocarcinoma: 20-year experience at
      a single institution.
AB  - BACKGROUND: Pancreatectomy for ductal adenocarcinoma has been performed with
      increasing frequency since the late 1980s as postoperative mortality decreased
      and long-term survival became more common. However, the belief persists among
      some clinicians that pancreatectomy offers little survival benefit. This report
      reviews our institutional experience with pancreatectomy for pancreatic
      adenocarcinoma and provides a critical overview of the controversies regarding
      the benefits of surgical intervention for patients who are candidates for
      curative resection. METHODS: We determined the survival of 142 patients who
      underwent pancreatectomy for ductal adenocarcinoma with curative intent (stage IA
      IIB) at Moffitt Cancer Center during the last two decades by using data obtained
      from review of the medical record, the Moffitt Cancer Registry, and the Social
      Security Death Index. Histologic diagnosis was confirmed by expert review of
      stained sections cut from fixed surgical specimens. RESULTS: In the 137 patients
      who survived at least 30 days after surgery, the median survival was 21.2 months
      after resection, with Kaplan-Meier 3- and 5-year disease-specific survival rates
      of 36% and 32%, respectively. One patient has survived without evidence of
      recurrent disease for more than 15 years after pancreatectomy. Survival for
      patients greater than 75 year of age did not differ from that of younger
      patients. The postoperative mortality rate was 1.5% during the most recent years
      of highest operative volume (2003 to 2006) and 3.5% for the entire patient
      cohort. CONCLUSIONS: Review of our 20-year experience with resection of
      pancreatic adenocarcinoma indicates that pancreatectomy with curative intent
      offers a real chance of long-term survival to patients with this highly lethal
      disease for which there is no other curative modality.

PMID- 18813197
TI  - Borderline resectable pancreatic cancer: on the edge of survival.
AB  - BACKGROUND: Patients with borderline resectable pancreatic cancer are at high
      risk of having positive surgical margins due to involvement of the tumor with
      adjacent vasculature. This article reviews the management of this subset of
      pancreatic cancer patients. METHODS: The authors review the current definitions
      of borderline resectable pancreatic cancer and how it is diagnosed and staged.
      The history, current approaches, and future directions in neoadjuvant therapy for
      borderline resectable pancreatic cancer are also reviewed with emphasis on
      various chemotherapy regimens that have been used. The application of intensity
      modulated radiation therapy and image-guided radiation therapy that accounts for
      respiratory motion to targeting the gross tumor volume in the pancreas are
      discussed, and the promise of integrating targeted therapies in neoadjuvant
      treatment programs is highlighted. RESULTS: The use of neoadjuvant treatment
      programs that employ gemcitabine-based chemotherapy regimens followed by
      chemoradiation increases the likelihood of subsequent margin-negative resection
      in borderline resectable pancreatic cancer. CONCLUSIONS: There has been progress
      in the imaging, staging, surgical technique, and the use of chemotherapy and
      chemoradiotherapy in the management of borderline resectable pancreatic cancer.
      Patients can benefit from multidisciplinary management at high-volume pancreatic
      cancer treatment centers.

PMID- 18813198
TI  - Cancer of the pancreas: are we making progress? A review of studies in the US
      Oncology Research Network.
AB  - BACKGROUND: Pancreatic cancer is the fourth leading cause of cancer deaths in the
      United States. In 2008, approximately 37,680 people will be diagnosed with
      pancreatic cancer and 34,290 will die of this disease. METHODS: The authors
      reviewed the literature on treatment of pancreatic cancer with an emphasis on
      studies conducted in the US Oncology Research (USOR) Network. RESULTS: Although
      much research has been conducted to develop improved systemic therapies of
      pancreatic cancer, gemcitabine as a single agent remains the current standard of
      care. Combinations with other chemotherapeutic drugs or biological agents have
      resulted in limited improvement. CONCLUSIONS: Despite aggressive efforts to
      improve treatment for patients with pancreatic cancer, limited progress has been
      made. It is hoped that new studies being planned and conducted will improve
      outcomes for patients with this disease.

PMID- 18813199
TI  - Aggressive surgical resection in the management of pancreatic neuroendocrine
      tumors: when is it indicated?
AB  - BACKGROUND: Pancreatic neuroendocrine tumors (PNETs) comprise a heterogeneous
      group of neoplasms for which treatment is variable, depending on the clinical
      stage. Despite this diversity, surgery remains the gold standard in the
      management of PNETs. This paper discusses whether aggressive surgical
      intervention is indicated for PNETs and investigates what prognostic factors may
      assist in predicting which patients with invasive disease will benefit most from
      surgical intervention. METHODS: A review was conducted of large surgical series
      reported in the English literature over the last 10 years as they pertain to
      current surgical intervention in PNETs and of prognostic factors related to
      surgical outcome and survival. RESULTS: Improved survival can be achieved with
      aggressive surgical management of PNETs. The presence of hepatic metastases is
      not a contraindication to surgical resection of the primary PNET. Results of
      series that reported prognostic factors are heterogeneous. CONCLUSIONS:
      Aggressive surgical resection for selected individuals with PNETs can be
      performed safely and may improve both symptomatic disease and overall survival.
      Consideration for resection of primary PNETs should be given to patients with
      treatable hepatic metastases. Prognostic indices such as tumor differentiation
      and ability to achieve R0/R1 resection have been linked to survival outcome in
      PNETs and should be considered when planning aggressive surgical management for
      this disease.

PMID- 18813200
TI  - Interdisciplinary management of an intraductal papillary mucinous neoplasm of the
      pancreas.
AB  - BACKGROUND: Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is
      less common than classic invasive ductal adenocarcinoma of the pancreas but is
      being diagnosed with greater frequency since its clinicopathologic features are
      now clearly defined. Often multifocal in its existence along the pancreatic duct,
      IPMN is associated with a significant risk for recurrence and warrants vigilant
      surveillance, even after a margin-negative resection. METHODS: The authors
      present a case highlighting important features in the diagnosis, workup, and
      management of IPMN. They also review existing literature highlighting
      epidemiology, findings of molecular studies, and current treatment
      recommendations. RESULTS: Physicians and patients must carefully weigh the risks
      and benefits associated with treatment options. Limited resection in a patient
      with a high likelihood of multifocal disease preserves pancreatic parenchyma and
      reduces the risk of developing pancreatic endocrine and exocrine insufficiency.
      Though the risk of developing invasive cancer in the remnant is small, the
      prognosis is worse if it does develop. Conversely, total pancreatectomy
      eliminates the risk of future malignancy but involves life-long insulin and
      exogenous pancreatic enzyme dependence and significant associated morbidity.
      CONCLUSIONS: Decision making for effective treatment of IPMN is complex and
      requires attention to detail by an interdisciplinary team with experience in the
      diagnosis and management of these tumors. Treatment must be individualized based
      on patient life expectancy in terms of remaining years and overall quality.
      Molecular profiling of these lesions may allow for more precise tailoring of
      treatment in the future.

PMID- 18813201
TI  - Willingness to participate in cancer screenings: blacks vs whites vs Puerto Rican
      Hispanics.
AB  - BACKGROUND: In the United States, blacks and Hispanics have lower cancer
      screening rates than whites have. Studies on the screening behaviors of
      minorities are increasing, but few focus on the factors that contribute to this
      discrepancy. This study presents the self-reported willingness by blacks, Puerto
      Rican Hispanics, and non-Hispanic whites to participate in cancer screenings in
      differing cancer screening situations. METHODS: The Cancer Screening
      Questionnaire (CSQ), a 60-item questionnaire, was administered via random-digit
      dial telephone interviews to adults in three cities: Baltimore, Maryland; New
      York, New York; and, San Juan, Puerto Rico. RESULTS: The 1,148 participants in
      the CSQ study sample consisted of 355 blacks, 311 Puerto Rican Hispanics, and 482
      non-Hispanic whites. Response rates ranged from 45% to 58% by city. Multivariable
      logistic regression analyses revealed that blacks and Puerto Ricans were often
      more likely (OR 2.0-3.0) and never less likely than whites to self-report
      willingness to participate in cancer screenings regardless of who conducted the
      cancer screening, what one was asked to do in the cancer screening, or what type
      of cancer was involved (with the exception of skin cancer where blacks, compared
      with whites, had an OR of 0.5). CONCLUSIONS: The findings from this study provide
      evidence that blacks and Hispanics self-report that they are either as willing or
      more willing than whites to participate in cancer screening programs.

PMID- 18813202
TI  - Participation in biomedical research studies and cancer screenings: perceptions
      of risks to minorities compared with whites.
AB  - BACKGROUND: This analysis was conducted to determine whether there is a
      difference among blacks, Hispanics, and whites in their perception of risks
      associated with participating in either a biomedical study or a cancer screening.
      METHODS: The Tuskegee Legacy Project Questionnaire, which focused on research
      subject participation, was administered in two different surveys (1999-2000 and
      2003) in seven cities. The Cancer Screening Questionnaire was administered in
      2003 in three cities. RESULTS: The study sample across the three surveys
      consisted of 1,064 blacks, 781 Hispanics, and 1,598 non-Hispanic whites. Response
      rates ranged from 44% to 70% by city. Logistic regression analyses, adjusted for
      age, sex, education, income, and city, revealed that blacks and Hispanics each
      self-reported that minorities, compared with whites, are more likely to be "taken
      advantage of" in biomedical studies and much less likely to get a "thorough and
      careful examination" in a cancer screening (odds ratios ranged from 3.6 to 14.2).
      CONCLUSIONS: Blacks and Hispanics perceive equally high levels of risk for
      participating in cancer screening examinations and for volunteering to become
      research subjects in biomedical studies. This perception provides a strong
      message about the need to overtly address this critical health disparities issue.

PMID- 18813203
TI  - Management of nerve sheath tumors arising in the sympathetic chain.
AB  - BACKGROUND: Extradural schwannomas arising from the sympathetic chain are
      uncommon benign nerve sheath tumors. We present our experience with three
      patients having such tumors located in the cervical, thoracic and lumbar regions
      and we describe clinical presentation, surgical treatment, and outcomes. METHODS:
      Between 2002 and 2006, the medical records of three patients with pathologically
      proven sympathetic schwannomas at the Moffitt Cancer Center were reviewed
      retrospectively. RESULTS: The three patients were female, with a mean age of 44
      years. Presentation and symptomatology varied between patients, and radiographic
      findings were not diagnostic. Complete excision of tumors was performed in all
      three patients without added morbidity or mortality. Surgical observation,
      histopathology, and immunohistochemistry confirmed the tumors to be schwannomas
      arising from the sympathetic chain. The schwannomas had a mean diameter of 3.2 cm
      and were all benign. At a mean follow-up of 21 months following resection, all
      patients remained free of disease recurrence. CONCLUSIONS: Sympathetic
      schwannomas are rare tumors that are difficult to diagnose preoperatively.
      Diagnosis relies on clinical suspicion, and confirmation is often obtained by
      means of surgical pathology. Long-term surveillance is not recommended and
      surgical excision should be considered for this tumor, even though the tumor is
      considered benign and recurrence is rare.

PMID- 18813204
TI  - Challenges in myelodysplastic syndromes: raising awareness and promoting new
      insight in therapeutic options.

PMID- 18813205
TI  - Myelodysplastic syndromes: diagnosis and staging.
AB  - Myelodysplastic syndromes (MDS) represent a heterogeneous group of hematologic
      disorders characterized by ineffective hematopoiesis and an increased risk of
      developing acute myelogenous leukemia (AML). Accurate diagnosis of MDS can be
      difficult, and its classification requires evaluation of cytopenias, bone marrow
      morphology, blast percentage, and cytogenetics. These factors, as well as patient
      performance status and red blood cell transfusion dependence, can be used to
      predict prognosis in MDS. Accurate diagnosis and classification are essential for
      subgroup identification and prognostic assessment of patients with MDS. This
      article reviews essential criteria for staging and subgroup classification and
      summarizes prognostic scoring systems that aid in risk stratification and
      selection of optimal therapy. Classification systems such as the World Health
      Organization (WHO) classification are widely used but do not always provide
      sufficient prognostic information. This limitation led to the creation of the
      International Prognostic Scoring System (IPSS). However, this system was designed
      to be used only at diagnosis and may not be suitable for serial assessment of
      patients whose disease can evolve over time. The WHO classification-based
      prognostic scoring system (WPSS) permits dynamic estimation of survival and risk
      of AML transformation at multiple time points during the natural course of MDS.
      Prognostic scoring systems such as WPSS allow for prediction of survival and risk
      of leukemic evolution at any time during the course of the disease. Such an
      approach may provide a useful adjunct for clinical decision making, including
      selection of appropriate treatment options.

PMID- 18813206
TI  - Changing the treatment paradigm in myelodysplastic syndromes.
AB  - The treatment algorithm for the patient with myelodysplastic syndrome (MDS) is in
      the process of being revitalized based on recent results of clinical trials.
      Historically, the goal for lower-risk patients was hematologic improvement, and
      disease modification was reserved for patients in the higher-risk category.
      Recent data now favor shifting emphasis away from supportive care alone and
      toward altering the disease course and prolonging survival, particularly in
      patients with intermediate-2 and high-risk disease. In addition, there is a
      greater appreciation for the significant morbidity and mortality resulting from
      MDS and increased efforts to improve quality of life while pursuing treatment.
      Immunomodulation with lenalidomide has yielded durable cytogenetic and
      hematologic responses and also has shown potential to alter disease course.
      Similarly, immunosuppression with antithymocyte globulin has shown sustained
      hematologic responses in selected patient subgroups. The methyltransferase
      inhibitors have demonstrated the ability to alter the natural history of disease
      and thus prolong time to leukemic transformation. In addition, azacitidine has
      shown the capacity to extend survival compared with the previous gold standard of
      conventional care regimens. With these new data, evaluation of treatment options
      should no longer focus on response rates as the sole endpoint but rather on time
      to leukemic transformation and survival. Timing of available therapies, including
      stem cell transplantation, should be incorporated into the new treatment
      paradigm, with end goals of prolonging survival and optimizing patient outcomes.

PMID- 18813207
TI  - Treatment strategies to optimize clinical benefit in the patient with
      myelodysplastic syndromes.
AB  - In recent years we have witnessed a transformation in care for patients with
      myelodysplastic syndromes (MDS) following approval by the US Food and Drug
      Administration of the first agents for treatment of the disease. Emerging
      evidence indicates that active treatment strategies modify the natural history of
      the underlying disease and hence lower the potential for leukemic transformation
      while prolonging survival. The methyltransferase inhibitor (MTI) azacitidine, in
      particular, has shown the capacity to extend survival in higher-risk disease in a
      post-approval phase III trial while demonstrating an improved risk/benefit
      profile in a new dosing schedule. By utilizing an MTI as a bridge to
      transplantation, allogeneic stem cell transplantation can now be postponed for
      appropriate candidates until a suitable donor is identified. Results of iron
      chelation studies indicate that the improved compliance of an oral iron chelator
      yields greater iron storage reduction with sustained suppression of the labile
      plasma form. The current active treatment paradigm for MDS incorporates the most
      recent strategies yielding improved disease outcomes and patient survival.

PMID- 18813208
TI  - Future directions in myelodysplastic syndrome: newer agents and the role of
      combination approaches.
AB  - Myelodysplastic syndrome (MDS) is not a single disease, but a collection of
      hematopoietic disorders that require newer strategies. Currently, azacitidine,
      decitabine, and lenalidomide are approved by the US Food and Drug Administration
      for the treatment of MDS. A recent study demonstrated an improved overall
      survival (24.4 months vs 15 months) in high-risk MDS patients receiving
      azacitidine plus best supportive care vs conventional care which has resulted in
      an updated label for this product. Conventional care consisted of supportive care
      alone or either low-dose ara-C or standard chemotherapy plus best supportive
      care. While these data are encouraging, newer agents such as vorinostat,
      MGCD0103, MS-275, and tipifarnib are currently being studied as monotherapy or in
      combinations with approved treatments for MDS. The goal of combining
      pharmacotherapy, such as the combination of DNA methylation inhibitors and
      histone deacetylase inhibitors, in the management of MDS is to increase the
      response rates and decrease the toxicities associated with treatment. Clinical
      experience in the use of combination products has given practitioners the
      empirical knowledge necessary to better treat patients with MDS. Utilizing
      convergent or complementary molecular mechanisms with in vitro or in vivo
      evidence of synergy is a fresher and maybe a more efficacious approach to
      combination therapy.

PMID- 18813209
TI  - Amyloid-beta causes memory impairment by disturbing the JAK2/STAT3 axis in
      hippocampal neurons.
AB  - Elevation of intracranial soluble amyloid-beta (Abeta) levels has been implicated
      in the pathogenesis of Alzheimer's disease (AD). Intracellular events in neurons,
      which lead to memory loss in AD, however, remain elusive. Humanin (HN) is a short
      neuroprotective peptide abolishing Abeta neurotoxicity. Recently, we found that
      HN derivatives activate the Janus kinase 2 (JAK2)/signal transducer and activator
      of transcription 3 (STAT3) signaling axis. We here report that an HN derivative
      named colivelin completely restored cognitive function in an AD model (Tg2576) by
      activating the JAK2/STAT3 axis. In accordance, immunofluorescence staining using
      a specific antibody against phospho- (p-) STAT3 revealed that p-STAT3 levels in
      hippocampal neurons age-dependently decreased in both AD model mice and AD
      patients. Intracerebroventricular administration of Abeta1-42 downregulated p
      STAT3 whereas passive immunization with anti-Abeta antibody conversely restored
      hippocampal p-STAT3 levels in Tg2576 mice, paralleling the decrease in the brain
      Abeta burden. Abeta1-42 consistently modulated p-STAT3 levels in primary neurons.
      Pharmacological inhibition of the JAK2/STAT3 axis not only induced significant
      loss of spatial working memory by downregulating an acetylcholine-producing
      enzyme choline acetyltransferase but also desensitized the M(1)-type muscarinic
      acetylcholine receptor. Thus, we propose a novel theory accounting for memory
      impairment related to AD: Abeta-dependent inactivation of the JAK2/STAT3 axis
      causes memory loss through cholinergic dysfunction. Our findings provide not only
      a novel pathological hallmark in AD but also a novel target in AD therapy.

PMID- 18813211
TI  - A case of cardiogenic shock caused by capecitabine treatment.
AB  - BACKGROUND: A 52-year-old woman underwent successful resection of stage IIB
      primary mucinous adenocarcinoma of the appendix and was started on capecitabine
      chemotherapy. Five days into the first course, after initially experiencing
      diarrhea, nausea, vomiting and a transient episode of retrosternal chest pain
      radiating to the left scapula, she presented to the emergency department with
      cardiogenic shock. INVESTIGATIONS: Electrocardiography, transthoracic
      echocardiography, laboratory investigation of cardiac biomarkers, coronary
      angiography and endomyocardial biopsy. DIAGNOSIS: Capecitabine-induced
      cardiogenic shock. MANAGEMENT: Supportive treatment with dopamine, milrinone,
      norepinephrine (noradrenaline) and levosimendan.

PMID- 18813210
TI  - Analysis of 10 independent samples provides evidence for association between
      schizophrenia and a SNP flanking fibroblast growth factor receptor 2.
AB  - We and others have previously reported linkage to schizophrenia on chromosome
      10q25-q26 but, to date, a susceptibility gene in the region has not been
      identified. We examined data from 3606 single-nucleotide polymorphisms (SNPs)
      mapping to 10q25-q26 that had been typed in a genome-wide association study
      (GWAS) of schizophrenia (479 UK cases/2937 controls). SNPs with P<0.01 (n=40)
      were genotyped in an additional 163 UK cases and those markers that remained
      nominally significant at P<0.01 (n=22) were genotyped in replication samples from
      Ireland, Germany and Bulgaria consisting of a total of 1664 cases with
      schizophrenia and 3541 controls. Only one SNP, rs17101921, was nominally
      significant after meta-analyses across the replication samples and this was
      genotyped in an additional six samples from the United States/Australia, Germany,
      China, Japan, Israel and Sweden (n=5142 cases/6561 controls). Across all
      replication samples, the allele at rs17101921 that was associated in the GWAS
      showed evidence for association independent of the original data (OR 1.17 (95% CI
      1.06-1.29), P=0.0009). The SNP maps 85 kb from the nearest gene encoding
      fibroblast growth factor receptor 2 (FGFR2) making this a potential
      susceptibility gene for schizophrenia.

PMID- 18813212
TI  - Interplay between impaired calcium regulation and insulin signaling abnormalities
      in diabetic cardiomyopathy.
AB  - According to the International Diabetes Federation the number of people between
      the ages of 20 and 79 years diagnosed with diabetes mellitus is projected to
      reach 380 million worldwide by 2025. Cardiovascular disease, including heart
      failure, is the major cause of death in patients with diabetes. A contributing
      factor to heart failure in such patients is the development of diabetic
      cardiomyopathy--a clinical myocardial condition distinguished by ventricular
      dysfunction that can present independently of other risk factors such as
      hypertension or coronary artery disease. This disorder has been associated with
      both type 1 and type 2 diabetes, and is characterized by early-onset diastolic
      dysfunction and late-onset systolic dysfunction. The development of diabetic
      cardiomyopathy and the cellular and molecular perturbations associated with the
      pathology are complex and multifactorial. Hallmark mechanisms include
      abnormalities in regulation of calcium homeostasis, and associated abnormal
      ventricular excitation-contraction coupling, metabolic disturbances, and
      alterations in insulin signaling. An emerging concept is that disruptions in
      calcium homeostasis might be linked to diminished insulin responsiveness. An
      understanding of the cellular effect of these abnormalities on cardiomyocytes
      should be useful in predicting the maladaptive cardiac structural and functional
      consequences of diabetes.

PMID- 18813213
TI  - Association between BBS6/MKKS gene polymorphisms, obesity and metabolic syndrome
      in the Greek population.
AB  - OBJECTIVE: To investigate the relationship between MKKS gene variations, obesity
      related traits and features of the metabolic syndrome (MS) in the Greek
      population. DESIGN AND SUBJECTS: Genotype and haplotype analysis was carried out
      for six known MKKS gene polymorphisms (534C>T, 985+16T>G, 985+33C>G, 986-29A>T,
      1161+58A>G and 1595G>T) in 220 obese subjects (body mass index > or =30 kg/m(2))
      and 330 non-obese controls. RESULTS: Genotype frequencies of the 985+16T>G, 986
      29A>T and 1595G>T SNPs were significantly different between obese and non-obese
      individuals (P=0.0016, 0.0196 and 0.0069, respectively). Obese carriers of the
      risk alleles of the above three polymorphisms had a significantly increased
      prevalence of arterial hypertension. Furthermore, obese carriers of the G allele
      for the 985+16T>G polymorphism had an increased prevalence of type 2 diabetes
      mellitus and of MS component traits. A new polymorphism was detected, namely a C
      to T substitution at position 1129 (1129C>T or N377N). Frequency of the T allele
      for the 1129C>T polymorphism was significantly higher in control individuals than
      in obese subjects (P=0.0253). Haplotype TGTGT was more prevalent in obese than in
      controls (P=0.0002) and was associated with increased prevalence of the MS in
      obese subjects (P<0.0001). CONCLUSION: Our results suggest that genetic variation
      in the MKKS gene may play a role in the development of obesity and the metabolic
      syndrome.

PMID- 18813214
TI  - Can the fractional excretion of uric acid distinguish the etiology of
      hyponatremia in patients taking diuretics?

PMID- 18813215
TI  - Metformin therapy for gestational diabetes mellitus: are we there yet?
AB  - Metformin is an effective alternative to insulin for nonpregnant women with type
      2 diabetes mellitus; however, it has not yet been studied in the setting of
      gestational diabetes mellitus (GDM). Concerns have been raised about the effect
      of metformin on fetal development, particularly because it crosses the placenta.
      In this Practice Point commentary, I discuss the findings of an open-label,
      multicenter, prospective trial conducted by Rowan et al., in which women with GDM
      were randomly allocated to receive metformin (plus insulin when necessary) or
      insulin alone. The rate of a composite neonatal outcome and the efficiency of
      glycemic control were not significantly different between the groups. Compared
      with the insulin group, the prevalence of severe neonatal hypoglycemia was lower
      but the rate of preterm birth was higher in the metformin group. Of note, 46% of
      metformin-treated women required supplemental insulin. Although the results of
      this study are encouraging, further data are needed on the long-term safety of
      metformin before it can be considered as first-line therapy for women with GDM.

PMID- 18813217
TI  - Transpedicular percutaneous biopsy of vertebral body lesions: a series of 71
      cases.
AB  - STUDY DESIGN: This prospective study evaluates the effectiveness of
      transpedicular biopsy carried out under local anesthesia in obtaining diagnostic
      tissue from vertebral body lesions. OBJECTIVE: To describe the technique of
      percutaneous transpedicular biopsy carried out under local anesthesia under C-arm
      fluoroscopy and to report the author's experience. SETTING: Spine hospital,
      Ahmedabad, Gujarat, India. METHODS: Seventy-one patients who underwent
      transpedicular biopsy from T6 to S1 vertebral body lesions were evaluated. Biopsy
      specimens were obtained by passing a self-designed 5-mm diameter biopsy
      instrument through the pedicle into the site of the disease using C-arm
      fluoroscopy. Specimens were sent for histological and bacteriologic analyses.
      RESULTS: Biopsy was carried out for vertebral lesions of 51 men and 20 women.
      Sixteen of these lesions were seen in thoracic spine, 53 in lumbar and two in
      sacrum. The pathologic examinations revealed infections in 25, osteoporotic
      wedging in 21, metastasis in eight, plasmacytoma in three, multiple myeloma in
      four, non-Hodgkin's lymphoma in one and round cell tumor in one patient.
      Diagnosis was established in 63 of 71 patients (88.7%). Remaining eight patients
      were reported as chronic nonspecific inflammation, and were followed up for more
      than 6 months. CONCLUSION: Percutaneous transpedicular vertebral biopsy under
      local anesthesia is an important tool in the evaluation of vertebral body
      lesions, especially in older population and can be performed with minimal
      morbidity and high diagnostic yield as an outpatient procedure.

PMID- 18813218
TI  - What is the role of androgen deprivation therapy in the treatment of locally
      advanced prostate cancer?
AB  - This Practice Point commentary discusses the paper by Horwitz and colleagues,
      which reported the long-term results of the RTOG 92-02 trial in which patients
      with locally advanced, node-negative prostate cancer who were treated with
      neoadjuvant-concurrent hormone ablation therapy and external beam radiation
      therapy (70 Gy) were subsequently randomized to receive either no further
      androgen deprivation or long-term (2-year) goserelin therapy. The results at 10
      years confirm biochemical and clinical outcome benefits with the use of long-term
      androgen deprivation therapy for patients treated with conventional-dose
      radiotherapy. How these results should best be incorporated into dose-escalated
      radiotherapeutic approaches remains unclear, however, and this issue requires
      further investigation.

PMID- 18813219
TI  - Efficacy and safety of dutasteride, tamsulosin and their combination in a
      subpopulation of the CombAT study: 2-year results in Asian men with moderate-to
      severe BPH.
AB  - Although ethnicity-based differences in prostate size and physiology have been
      reported, results of benign prostatic hyperplasia (BPH) treatment trials in
      predominantly Caucasian patients are assumed to be applicable to non-Caucasian
      populations. This post hoc analysis investigated whether an Asian subpopulation
      of men with moderate-to-severe BPH in the CombAT study achieves treatment
      responses in line with those of the overall study population. In this double
      blind, randomized, parallel-group trial, 325 Asian men were assigned to treatment
      with 0.5 mg dutasteride once daily, 0.4 mg tamsulosin once daily or the
      combination. Decrease in international prostate symptom score (IPSS) at month 24
      from baseline (the primary endpoint) was significantly greater with combination
      treatment compared with tamsulosin (P<0.05), and numerically, but not
      statistically significantly, greater compared with dutasteride. Mean IPSS was
      reduced from baseline by 7.5 (+/-0.84) in the combination group, by 6.3 (+/-0.86)
      in the dutasteride group and by 4.5 (+/-0.78) in the tamsulosin group, resulting
      in respective mean IPSS at months 24 of 11.4 (+/-0.60), 12.7 (+/-0.70) and 14.3
      (+/-0.74). The adverse event profile was similar to that observed in the overall
      CombAT population, and drug-related adverse events were more common with
      combination therapy (26%) than with tamsulosin (15%) or dutasteride (9%). No
      unexpected adverse events emerged. In conclusion, in Asian men with moderate-to
      severe lower urinary tract symptoms and an enlarged prostate, combination therapy
      achieved significantly greater improvements from baseline BPH symptoms, flow
      rate, quality of life, reduced prostate volume and improved treatment
      satisfaction compared with tamsulosin monotherapy.

PMID- 18813220
TI  - Therapeutic advances in rheumatology with the use of recombinant proteins.
AB  - Antibody engineering and protein design have led to the creation of a new era of
      targeted anti-inflammatory therapies in rheumatology. Recombinant DNA
      technologies have enabled the selection and humanization of specific antibody
      fragments in order to develop therapeutic reagents of any specificity that can be
      'armed' to deliver effective anti-inflammatory 'payloads'. Antibodies and
      antibody-like proteins provide the opportunity to block key soluble mediators of
      inflammation in their milieu, or alternatively to block intracellular
      inflammation-triggering pathways by binding to an upstream cell-surface receptor.
      These designer proteins can be tuned for desired pharmacokinetic and
      pharmacodynamic effects, and represent tools for specific therapeutic
      intervention by delivering precisely the required immunosuppressive effect. The
      extent of desired and undesired effects of a particular biologic therapy,
      however, can be broader than initially predicted and require careful evaluation
      during clinical trials. This Review highlights advances in recombinant
      technologies for the development of novel biologic therapies in rheumatology.

PMID- 18813221
TI  - Mechanisms of infectious diarrhea.
AB  - Infectious diarrhea is an important public health problem worldwide. Research has
      provided new insights into the mechanisms of diarrhea caused by various pathogens
      that are classified as noninflammatory, inflammatory or invasive. These three
      groups of organisms cause two diarrheal syndromes--noninflammatory diarrhea and
      inflammatory diarrhea. The noninflammatory diarrheas are caused by enterotoxin
      producing organisms such as Vibrio cholerae and enterotoxigenic Escherichia coli,
      or by viruses that adhere to the mucosa and disrupt the absorptive and/or
      secretory processes of the enterocyte without causing acute inflammation or
      mucosal destruction. Inflammatory diarrhea is caused by two groups of organisms-
      cytotoxin-producing, noninvasive bacteria (e.g. enteroaggregative Escherichia
      coli, enterohemorrhagic Escherichia coli and Clostridium difficile), or by
      invasive organisms (e.g. Salmonella spp., Shigella spp., Campylobacter spp.,
      Entamoeba histolytica). The cytotoxin-producing organisms adhere to the mucosa,
      activate cytokines and stimulate the intestinal mucosa to release inflammatory
      mediators. Invasive organisms, which can also produce cytotoxins, invade the
      intestinal mucosa to induce an acute inflammatory reaction, involving the
      activation of cytokines and inflammatory mediators. Regardless of the underlying
      mechanism they use, these various types of pathogen have all successfully evolved
      to evade and modulate the host defense systems. The mechanisms by which the
      different pathogens invade the host and cause infectious diarrhea are the topic
      of this Review.

PMID- 18813222
TI  - Does long-term PPI use result in vitamin B12 deficiency in elderly individuals?

PMID- 18813223
TI  - Who should receive antibiotic prophylaxis before ERCP?

PMID- 18813224
TI  - Is probiotic prophylaxis worthwhile in patients with predicted severe acute
      pancreatitis?

PMID- 18813225
TI  - Enhancement of RNAi by a small molecule antibiotic enoxacin.

PMID- 18813226
TI  - Construction of a chloroplast protein interaction network and functional mining
      of photosynthetic proteins in Arabidopsis thaliana.
AB  - Chloroplast is a typical plant cell organelle where photosynthesis takes place.
      In this study, a total of 1,808 chloroplast core proteins in Arabidopsis thaliana
      were reliably identified by combining the results of previously published studies
      and our own predictions. We then constructed a chloroplast protein interaction
      network primarily based on these core protein interactions. The network had
      22,925 protein interaction pairs which involved 2,214 proteins. A total of 160
      previously uncharacterized proteins were annotated in this network. The subunits
      of the photosynthetic complexes were modularized, and the functional
      relationships among photosystem I (PSI), photosystem II (PSII), light harvesting
      complex of photosystem I (LHC I) and light harvesting complex of photosystem I
      (LHC II) could be deduced from the predicted protein interactions in this
      network. We further confirmed an interaction between an unknown protein AT1G52220
      and a photosynthetic subunit PSI-D2 by yeast two-hybrid analysis. Our chloroplast
      protein interaction network should be useful for functional mining of
      photosynthetic proteins and investigation of chloroplast-related functions at the
      systems biology level in Arabidopsis.

PMID- 18813227
TI  - Structural basis for dsRNA recognition by NS1 protein of influenza A virus.
AB  - Influenza A viruses are important human pathogens causing periodic pandemic
      threats. Nonstructural protein 1 (NS1) protein of influenza A virus (NS1A)
      shields the virus against host defense. Here, we report the crystal structure of
      NS1A RNA-binding domain (RBD) bound to a double-stranded RNA (dsRNA) at 1.7A.
      NS1A RBD forms a homodimer to recognize the major groove of A-form dsRNA in a
      length-independent mode by its conserved concave surface formed by dimeric anti
      parallel alpha-helices. dsRNA is anchored by a pair of invariable arginines
      (Arg38) from both monomers by extensive hydrogen bonds. In accordance with the
      structural observation, isothermal titration calorimetry assay shows that the
      unique Arg38-Arg38 pair and two Arg35-Arg46 pairs are crucial for dsRNA binding,
      and that Ser42 and Thr49 are also important for dsRNA binding. Agrobacterium co
      infiltration assay further supports that the unique Arg38 pair plays important
      roles in dsRNA binding in vivo.Cell Research (2009) 19:187-195. doi:
      10.1038/cr.2008.288; published online 23 September 2008.

PMID- 18813228
TI  - Cancer fatigue syndrome reflects clinically non-overt heart failure: an approach
      towards onco-cardiology.

PMID- 18813229
TI  - Neurological manifestations of Waldenstrom macroglobulinemia.
AB  - Waldenstrom macroglobulinemia, a condition that most commonly occurs in
      lymphoplasmacytic lymphoma, typically manifests with diffuse lymphadenopathies,
      cytopenias, and a markedly elevated erythrocyte sedimentation rate. Peripheral
      neuropathy occurs in nearly half of patients with this condition, and
      hyperviscosity-related nervous system disorders are encountered in up to a third.
      Other neurological complications, such as encephalopathy or myelopathy caused by
      direct tumor infiltration, paraprotein deposition or autoimmune phenomena, are
      rare. Diagnosis of Waldenstrom macroglobulinemia requires identification of
      monoclonal IgM protein in the serum, bone marrow biopsy, and appropriate
      neurological testing (e.g. imaging studies of affected areas of the central
      neuraxis, electrophysiological studies). Treatment options, which should address
      both the paraprotein burden and the lymphoplasmacytic clone, include
      plasmapheresis and chemotherapy with alkylating agents, nucleoside analogs, and
      rituximab. As the disease is incurable and its course indolent, these treatments
      are only provided to symptomatic patients.

PMID- 18813230
TI  - B cells as therapeutic targets in autoimmune neurological disorders.
AB  - B cells have a fundamental role in the pathogenesis of various autoimmune
      neurological disorders, not only as precursors of antibody-producing cells, but
      also as important regulators of the T-cell activation process through their
      participation in antigen presentation, cytokine production, and formation of
      ectopic germinal centers in the intermeningeal spaces. Two B-cell trophic factors
      BAFF (B-cell-activating factor) and APRIL (a proliferation-inducing ligand)-and
      their receptors are strongly upregulated in many immunological disorders of the
      CNS and PNS, and these molecules contribute to clonal expansion of B cells in
      situ. The availability of monoclonal antibodies or fusion proteins against B-cell
      surface molecules and trophic factors provides a rational approach to the
      treatment of autoimmune neurological diseases. This article reviews the role of B
      cells in autoimmune neurological disorders and summarizes the experience to date
      with rituximab, a B-cell-depleting monoclonal antibody against CD20, for the
      treatment of relapsing-remitting multiple sclerosis, autoimmune neuropathies,
      neuromyelitis optica, paraneoplastic neurological disorders, myasthenia gravis,
      and inflammatory myopathies. It is expected that ongoing controlled trials will
      establish the efficacy and long-term safety profile of anti-B-cell agents in
      several autoimmune neurological disorders, as well as exploring the possibility
      of a safe and synergistic effect with other immunosuppressants or
      immunomodulators.

PMID- 18813231
TI  - Islet transplantation: need for a time-out?

PMID- 18813232
TI  - KDIGO clinical practice guidelines on hepatitis C in chronic kidney disease
      acknowledged by ISN.

PMID- 18813233
TI  - Racial differences in chronic kidney disease incidence and progression among
      individuals with HIV.
AB  - This Practice Point commentary discusses the findings of Lucas et al.'s
      longitudinal cohort study of chronic kidney disease (CKD) in African American and
      white individuals with HIV. The study found that--compared with whites--African
      Americans had a slightly increased risk of incident CKD, but markedly increased
      rates of estimated glomerular filtration rate decline and progression to end
      stage renal disease. This commentary details the clinical implications and
      limitations of these findings in the context of known racial differences in CKD
      prevalence and progression to end-stage renal disease in the general population
      and highlights the importance of screening high-risk HIV patients for kidney
      disease. CKD is common among HIV patients, and-as in the general population-has a
      more-aggressive course among African Americans than whites.

PMID- 18813234
TI  - Understanding the pathophysiology of hemodialysis access problems as a prelude to
      developing innovative therapies.
AB  - Maintenance of a functioning vascular access for hemodialysis is a major
      challenge for nephrologists, vascular surgeons and--most importantly--the
      patients themselves. Greater insight into the pathophysiology of access
      thrombosis, stenosis, aneurysm formation, fistula maturation failure and catheter
      infection will aid the development of innovative ways to prevent and treat these
      complications. According to the results of observational studies, agents that
      decrease the release of inflammatory mediators, improve endothelial function, and
      inhibit the migration and proliferation of vascular smooth-muscle cells might
      improve the maturation and survival of native hemodialysis fistulas and synthetic
      hemodialysis grafts by reducing the risks of thrombosis and stenosis. Currently
      available drugs that interfere with metalloproteinases could prevent the
      formation of aneurysms, and bacterial quorum sensing offers a promising target
      for the prevention of biofilm infection in hemodialysis catheters.

PMID- 18813235
TI  - Animal toxins and the kidney.
AB  - Envenomation or poisoning by toxins from animals poses an important health hazard
      in the tropics. Animal toxins are complex mixtures of proteins, peptides, enzymes
      and chemicals. These toxins exert their effects through modulation of ion
      channels and receptors, and via direct enzyme action. Depolarization or
      hyperpolarization of ion channels--caused by most marine toxins, and some snake
      and insect venoms--results in neuromuscular symptoms that can be associated with
      hemodynamic changes. Toxin enzymes, especially proteases and phospholipase A2,
      initiate inflammatory processes that involve the generation of proinflammatory
      cytokines and vasoactive mediators, resulting in systemic and renal hemodynamic
      alterations. Toxin enzymes also have direct effects on erythrocytes, myocytes,
      blood coagulation factors, vascular endothelium and epithelial cells. As a
      result, disseminated intravascular coagulation, bleeding diathesis, intravascular
      hemolysis and rhabdomyolysis are common after exposure to animal toxins. The
      renal manifestations of animal toxin envenomation, which are usually acute,
      result mainly from these enzymatic effects. All renal structures can be affected
      by animal toxins, and tubular necrosis is common. Acute kidney injury is
      attributed to decreased renal blood flow (associated with intravascular hemolysis
      or rhabdomyolysis), disseminated intravascular coagulation or direct tubular
      toxicity. Immunologic mechanisms have a minor role in the pathophysiology of
      nephropathy caused by animal toxins.

PMID- 18813236
TI  - Trends and inequalities in survival for 20 cancers in England and Wales 1986
      2001: population-based analyses and clinical commentaries. Foreword.

PMID- 18813237
TI  - Survival from brain tumours in England and Wales up to 2001.

PMID- 18813238
TI  - Survival from non-Hodgkin lymphoma in England and Wales up to 2001.

PMID- 18813239
TI  - Survival from non-Hodgkin lymphoma in England and Wales up to 2001.

PMID- 18813240
TI  - Survival from cancer of the oesophagus in England and Wales up to 2001.

PMID- 18813241
TI  - Survival from multiple myeloma in England and Wales up to 2001.

PMID- 18813242
TI  - Survival from multiple myeloma in England and Wales up to 2001.

PMID- 18813243
TI  - Survival from adult leukaemia in England and Wales up to 2001.

PMID- 18813244
TI  - Survival from adult leukaemia in England and Wales up to 2001.

PMID- 18813245
TI  - Survival from cancer of the oesophagus in England and Wales up to 2001.

PMID- 18813246
TI  - Survival from cancer of the stomach in England and Wales up to 2001.

PMID- 18813247
TI  - Survival from cancer of the stomach in England and Wales up to 2001.

PMID- 18813249
TI  - Survival from cancer of the pancreas in England and Wales up to 2001.

PMID- 18813248
TI  - Cancer survival in England and Wales at the end of the 20th century.
AB  - Survival has risen steadily since the 1970s for most cancers in adults in England
      and Wales, but persistent inequalities exist between those living in affluent and
      deprived areas. These differences are not seen for children. For many of the
      common adult cancers, these inequalities in survival (the 'deprivation gap')
      became more marked in the 1990s. This volume presents extended analyses of
      survival for adults diagnosed during the 14 years 1986-1999 and followed up to
      2001, including trends in overall survival in England and Wales and trends in the
      deprivation gap in survival. The analyses include individual tumour data for 2.2
      million cancer patients. This article outlines the structure of the supplement -
      an article for each of the 20 most common cancers in adults, followed by an
      expert commentary from one of the leading UK clinicians specialising in
      malignancies of that organ or system. The available data, quality control and
      methods of analysis are described here, rather than repeated in each of the 20
      articles. We open the discussion between clinicians and epidemiologists on how to
      interpret the observed trends and inequalities in cancer survival, and we
      highlight some of the most important contrasts in these very different points of
      view. Survival improved substantially for adult cancer patients in England and
      Wales up to the end of the 20th century. Although socioeconomic inequalities in
      survival are remarkably persistent, the overall patterns suggest that these
      inequalities are largely avoidable.

PMID- 18813250
TI  - Survival from cancer of the pancreas in England and Wales up to 2001.

PMID- 18813251
TI  - Survival from cancer of the colon in England and Wales up to 2001.

PMID- 18813252
TI  - Survival from cancer of the rectum in England and Wales up to 2001.

PMID- 18813253
TI  - Survival from cancers of the colon and rectum in England and Wales up to 2001.

PMID- 18813254
TI  - Survival from cancer of the larynx in England and Wales up to 2001.

PMID- 18813255
TI  - Survival from laryngeal cancer in England and Wales up to 2001.

PMID- 18813256
TI  - Survival from cancer of the lung in England and Wales up to 2001.

PMID- 18813257
TI  - Survival from lung cancer in England and Wales up to 2001.

PMID- 18813258
TI  - Survival from melanoma of the skin in England and Wales up to 2001.

PMID- 18813259
TI  - Survival from melanoma of the skin in England and Wales up to 2001.

PMID- 18813260
TI  - Survival from cancer of the breast in women in England and Wales up to 2001.

PMID- 18813261
TI  - Survival from breast cancer in England and Wales up to 2001.

PMID- 18813262
TI  - Survival from cancer of the uterine cervix in England and Wales up to 2001.

PMID- 18813263
TI  - Survival from cancer of the uterine cervix in England and Wales up to 2001.

PMID- 18813264
TI  - Survival from cancer of the uterus in England and Wales up to 2001.

PMID- 18813265
TI  - Survival from endometrial cancer in England and Wales up to 2001.

PMID- 18813266
TI  - Survival from cancer of the ovary in England and Wales up to 2001.

PMID- 18813267
TI  - Survival from cancer of the ovary in England and Wales up to 2001.

PMID- 18813268
TI  - Survival from prostate cancer in England and Wales up to 2001.

PMID- 18813269
TI  - Survival from prostate cancer in England and Wales up to 2001.

PMID- 18813270
TI  - Survival from testicular cancer in England and Wales up to 2001.

PMID- 18813271
TI  - Survival from testicular cancer in England and Wales up to 2001.

PMID- 18813272
TI  - Survival from bladder cancer in England and Wales up to 2001.

PMID- 18813273
TI  - Survival from bladder cancer in England and Wales up to 2001.

PMID- 18813274
TI  - Survival from cancers of the kidney and ureter in England and Wales up to 2001.

PMID- 18813275
TI  - Survival from kidney cancer in England and Wales up to 2001.

PMID- 18813276
TI  - Survival from brain tumours in England and Wales up to 2001.

PMID- 18813277
TI  - Correction of laminin-5 deficiency in human epidermal stem cells by
      transcriptionally targeted lentiviral vectors.
AB  - Deficiency of the basement membrane component laminin-5 (LAM5) causes junctional
      epidermolysis bullosa (JEB), a severe and often fatal skin adhesion defect.
      Autologous transplantation of epidermal stem cells genetically corrected with a
      Moloney leukemia virus (MLV)-derived retroviral vector reconstitutes LAM5
      synthesis, and corrects the adhesion defect in JEB patients. However, MLV-derived
      vectors have genotoxic characteristics, and are unable to reproduce the
      physiological, basal layer-restricted expression of LAM5 chains. We have
      developed an alternative gene transfer strategy based on self-inactivating (SIN)
      or long terminal repeat (LTR)-modified lentiviral vectors, in which transgene
      expression is under the control of different combinations of promoter-enhancer
      elements derived from the keratin-14 (K14) gene. Analysis in human keratinocyte
      cultures and in fully differentiated skin regenerated onto immunodeficient mice
      showed that gene expression directed by K14 enhancers is tissue-specific and
      restricted to the basal layer of the epidermis. Transcriptionally targeted
      lentiviral vectors efficiently transduced clonogenic stem/progenitor cells
      derived from a skin biopsy of a JEB patient, restored normal synthesis of LAM5 in
      cultured keratinocytes, and reconstituted normal adhesion properties in human
      skin equivalents transplanted onto immunodeficient mice. These vectors are
      therefore an effective, and potentially more safe, alternative to MLV-based
      retroviral vectors in gene therapy of JEB.Molecular Therapy (2008) 16 12, 1977
      1985 doi:10.1038/mt.2008.204.

PMID- 18813278
TI  - Biological pacemaker engineered by nonviral gene transfer in a mouse model of
      complete atrioventricular block.
AB  - We hypothesized that a nonviral gene delivery of the hyperpolarization-activated
      HCN2 channel combined with the beta(2)-adrenergic receptor (ADRB2) would generate
      a functional pacemaker in a mouse model of complete atrioventricular block (CAVB)
      induced by radiofrequency ablation of the His bundle. Plasmids encoding HCN2 and
      ADRB2 mixed with tetronic 304, a poloxamine block copolymer, were injected in the
      left ventricular free wall (HCN2-ADRB2 mice). Sham mice received a noncoding
      plasmid. CAVB was induced 5 days later. Ventricular escape rhythms in HCN2-ADRB2
      mice were significantly faster than in sham mice at day 15 after ablation and
      later. In HCN2-ADRB2 mice, QRS complexes were larger than in sham mice and
      characterized by abnormal axes. Immunostaining of GFP-HCN2 fusion protein showed
      an expression of HCN2 channel in left ventricular myocardium for at least 45 days
      after injection. In the mouse, CAVB induces progressive hypertrophy and heart
      failure leading to 50% mortality after 110 days. HCN2-ADRB2 mice survived 3 weeks
      longer than sham mice. Finally, beta-adrenergic input increased ventricular
      escape rhythms significantly more in HCN2-ADRB2 mice than in sham mice. In
      conclusion, nonviral gene transfer can produce a functional cardiac biological
      pacemaker regulated by sympathetic input, which improves life expectancy in a
      mouse model of CAVB.

PMID- 18813279
TI  - Potent systemic anticancer activity of adenovirally expressed EGFR-selective
      TRAIL fusion protein.
AB  - Previously, we demonstrated potent tumor cell-selective pro-apoptotic activity of
      scFv425:sTRAIL, a recombinant fusion protein comprised of EGFR-directed antibody
      fragment (scFv425) genetically fused to human soluble TNF-related apoptosis
      inducing ligand (sTRAIL). Here, we report on the promising therapeutic systemic
      tumoricidal activity of scFv425:sTRAIL when produced by the replication-deficient
      adenovirus Ad-scFv425:sTRAIL. In vitro treatment of EGFR-positive tumor cells
      with Ad-scFv425:sTRAIL resulted in the potent induction of apoptosis of not only
      infected tumor cells, but importantly also of up to 60% of noninfected EGFR
      positive tumor cells. A single intraocular injection of Ad-scFv425:sTRAIL in
      tumor-free nu/nu mice resulted in predominant liver infection and concomitant
      high blood plasma levels of scFv425:sTRAIL. These mice showed no sign of Ad
      scFv425:sTRAIL-related liver toxicity. Identical treatment of mice with
      established intraperitoneal renal cell carcinoma xenografts resulted in rapid and
      massive tumor load reduction and subsequent long-term survival. Taken together,
      adenoviral-mediated in vivo production of scFv425:sTRAIL may be exploitable for
      systemic treatment of EGFR-positive cancer.

PMID- 18813280
TI  - Efficient modulation of T-cell response by dual-mode, single-carrier delivery of
      cytokine-targeted siRNA and DNA vaccine to antigen-presenting cells.
AB  - Controlled modulation of T-cell response during immunotherapy, especially the
      balance between T helper 1 (Th1) and Th2 responses, is critical for generating
      effective immune response. Here we report that dual delivery of interleukin 10
      (IL-10)-targeted small interfering RNA (siRNA) and DNA vaccines to dendritic
      cells (DCs), using a single particle carrier, efficiently enhances immune
      response and modulates it toward a stronger Th1 phenotype. Surface-functionalized
      polymer microparticles (MPs) carrying both IL-10-targeted siRNA and DNA antigens
      exhibited effective gene silencing, DNA transfection, and synergistically
      enhanced upregulation of maturation markers in primary DCs leading to increased T
      cell proliferation, in vitro. Mice immunized with these dual-delivery carriers
      demonstrated a significant "switch" toward Th1 response as evidenced by increase
      in interferon gamma (IFN-gamma) production and decrease in IL-4 production by
      CD4+ T cells. This further led to enhanced antiviral cytotoxic T-lymphocyte
      activity. Such dual siRNA-DNA delivery provides a novel strategy to precisely
      control the type and strength of T-cell response during immunotherapy.

PMID- 18813281
TI  - Percutaneous transendocardial delivery of self-complementary adeno-associated
      virus 6 achieves global cardiac gene transfer in canines.
AB  - Achieving efficient cardiac gene transfer in a large animal model has proven to
      be technically challenging. Previous strategies have used cardiopulmonary bypass
      or dual catheterization with the aid of vasodilators to deliver vectors, such as
      adenovirus, adeno-associated virus (AAV), or plasmid DNA. Although single
      stranded AAV (ssAAV) vectors have shown the greatest promise, they suffer from
      delayed expression, which might be circumvented using self-complementary vectors.
      We sought to optimize cardiac gene transfer using a percutaneous transendocardial
      injection catheter to deliver adeno-associated viral vectors to the canine
      myocardium. Four vectors were evaluated--ssAAV9, self-complementary AAV9
      (scAAV9), scAAV8, scAAV6--so that comparison could be made between single
      stranded and self-complementary vectors as well as among serotypes 9, 8, and 6.
      We demonstrate that scAAV is superior to ssAAV and that AAV 6 is superior to the
      other serotypes evaluated. Biodistribution studies revealed that vector genome
      copies were 15-4,000 times more abundant in the heart than in any other organ for
      scAAV6. Percutaneous transendocardial injection of scAAV6 is a safe, effective
      method to achieve efficient cardiac gene transfer.

PMID- 18813282
TI  - Guidelines for antisense oligonucleotide design and insight into splice
      modulating mechanisms.
AB  - Antisense oligonucleotides (AONs) can interfere with mRNA processing through
      RNase H-mediated degradation, translational arrest, or modulation of splicing.
      The antisense approach relies on AONs to efficiently bind to target sequences and
      depends on AON length, sequence content, secondary structure, thermodynamic
      properties, and target accessibility. We here performed a retrospective analysis
      of a series of 156 AONs (104 effective, 52 ineffective) previously designed and
      evaluated for splice modulation of the dystrophin transcript. This showed that
      the guanine-cytosine content and the binding energies of AON-target and AON-AON
      complexes were significantly higher for effective AONs. Effective AONs were also
      located significantly closer to the acceptor splice site (SS). All analyzed AONs
      are exon-internal and may act through steric hindrance of Ser-Arg-rich (SR)
      proteins to exonic splicing enhancer (ESE) sites. Indeed, effective AONs were
      significantly enriched for ESEs predicted by ESE software programs, except for
      predicted binding sites of SR protein Tra2beta, which were significantly enriched
      in ineffective AONs. These findings compile guidelines for development of AONs
      and provide more insight into the mechanism of antisense-mediated exon skipping.
      On the basis of only four parameters, we could correctly classify 79% of all AONs
      as effective or ineffective, suggesting these parameters can be used to more
      optimally design splice-modulating AONs.

PMID- 18813284
TI  - Interpretation and review of health-related quality of life data in CKD patients
      receiving treatment for anemia.
AB  - Recent evidence suggests that targeting higher hemoglobin values with
      erythropoiesis stimulating agents (ESAs) may lack mortality benefits and may even
      result in adverse cardiovascular complications when used in chronic kidney
      disease patients. However, ESAs are frequently reported to result in improvements
      in health-related quality of life (HRQOL). The purpose of this review is to
      evaluate the magnitude and nature of ESA-associated improvements in HRQOL, as
      well as to understand how to interpret the clinical significance of HRQOL data.
      HRQOL findings should be analyzed not by statistical significance but rather by
      using a minimal clinically important difference approach, or, alternatively, a
      distribution-based approach (such as Cohen's effect size). HRQOL domains that are
      most improved with ESAs relate to physical symptoms, vitality, energy, and
      performance; domains of social functioning and mental health show modest
      improvement, whereas the domains of emotional functioning and pain show very
      little improvement. Additional domains not measured by commonly used instruments
      (such as the SF-36) that have been shown to improve with ESAs include sleep,
      cognitive functioning, and sexual functioning. The maximal increase in HRQOL per
      incremental increase in hemoglobin appears to occur in the range of 10-12 g/dl.
      Beyond this range, additional normalization of hemoglobin (to 12-14 g/dl) results
      in continued (albeit blunted) improvements in HRQOL.

PMID- 18813283
TI  - Parathyroid-specific interaction of the calcium-sensing receptor and G alpha q.
AB  - The calcium-sensing receptor regulates various parathyroid gland functions,
      including hormone secretion, gene transcription, and chief cell hyperplasia
      through G alpha q- and G alpha i-dependent signaling pathways. To determine the
      specific function of G alpha q in these processes, we generated transgenic mice
      using the human parathyroid hormone promoter to drive overexpression of a
      dominant negative G alpha q loop minigene to selectively disrupt G alpha q
      function in the parathyroid gland. The G alpha q loop mRNA was highly expressed
      in the parathyroid gland but not in other tissues of these transgenic mice. Gross
      appearance, body weight, bone mineral density, and survival of the transgenic
      mice were indistinguishable from those of their wild-type littermates. Adult
      transgenic mice, however, exhibited an increase in parathyroid hormone mRNA and
      in its basal serum level as well as in gland size. The response of the
      parathyroid gland to hypocalcemia was found to be reduced in sensitivity in the
      transgenic mice when compared to their wild-type controls. Abnormalities of the
      parathyroid gland function in these transgenic mice were similar to those of
      heterozygous G alpha q(+/-) and calcium sensing receptor(+/-) mice. These studies
      demonstrate the feasibility of selectively targeting the parathyroid gland to
      investigate signaling mechanisms downstream of the calcium receptor.

PMID- 18813285
TI  - Suppression of renin-angiotensin gene expression in the kidney by paricalcitol.
AB  - The renal renin-angiotensin system plays a major role in determining the rate of
      chronic renal disease progression. Treatment with activators of the vitamin D
      receptor retards the progression of experimental chronic renal disease, and
      vitamin D is known to suppress the renin-angiotensin system in other organs. Here
      we determined if the beneficial effects of paricalcitol (19-nor 1,25
      dihydroxyvitamin D(2)) were associated with suppression of renin-angiotensin gene
      expression in the kidney. Rats with the remnant kidney model of chronic renal
      failure (5/6 nephrectomy) were given two different doses of paricalcitol thrice
      weekly for 8 weeks. Paricalcitol was found to decrease angiotensinogen, renin,
      renin receptor, and vascular endothelial growth factor mRNA levels in the remnant
      kidney by 30-50 percent compared to untreated animals. Similarly, the protein
      expression of renin, renin receptor, the angiotensin type 1 receptor, and
      vascular endothelial growth factor were all significantly decreased. Glomerular
      and tubulointerstitial damage, hypertension, proteinuria, and the deterioration
      of renal function resulting from renal ablation were all similarly and
      significantly improved with both treatment doses. These studies suggest that the
      beneficial effects of vitamin D receptor activators in experimental chronic renal
      failure are due, at least in part, to down-regulation of the renal renin
      angiotensin system.

PMID- 18813287
TI  - Hypokalemia, metabolic alkalosis, and hypertension in a lung cancer patient.

PMID- 18813286
TI  - Effects of the renal medullary pH and ionic environment on vasopressin binding
      and signaling.
AB  - The kidney has a cortico-medullary interstitial gradient of decreasing pH and
      increasing concentrations of sodium chloride and urea, but the influence of these
      gradients on receptor signaling is largely unknown. Here, we measured G-protein
      coupled receptor function in LLC-PK1 cells acutely exposed to conditions
      mimicking different kidney regions. Signaling through the parathyroid hormone
      receptor, normally expressed in the cortex, was greatly reduced at an acidic pH
      similar to that of the inner medulla. Parathyroid hormone receptor, tagged with
      green fluorescent protein, showed no ligand-induced internalization. In contrast,
      under both acidic and hyperosmotic conditions, vasopressin increased
      intracellular cAMP, and upon binding to its type 2 receptor (V2R) was
      internalized and degraded. Dose-displacement binding assays with selective
      vasopressin/oxytocin receptor ligands under inner medullary conditions indicated
      a shift in the V2R pharmacological profile. Oxytocin did not bind to the V2R, as
      it does under normal conditions and the vasopressin type 1 receptor (V1R) had
      reduced affinity for vasopressin compared to the V2R in low pH and high
      osmolality. We suggest that the cortico-medullary gradient causes a receptor
      specific selectivity in ligand binding that is of functional significance to the
      kidney. While the gradient is important for urinary concentration, it may also
      play a substantial role in fine-tuning of the vasopressin response through the
      V2R.

PMID- 18813288
TI  - Status of chronic kidney disease prevention programs: International Federation of
      Kidney Foundation Members 2005/2007.
AB  - The International Federation of Kidney Foundations surveyed its members on
      chronic kidney disease 'prevention' programs in their regions and countries in
      2005 and 2007. A profile was developed, representing 28 countries (56% response).
      Some form of screening activity was reported in 24 of the 28 countries (85.7%).
      Two countries (7%) had, or anticipated development of, legislated national
      screening. Programs were conducted by kidney foundations or research groups, and
      were variously population based, focused on high risk groups or opportunistic.
      Tests in 63% of responding programs included weight, height, blood pressure,
      blood glucose, dipstick urinalysis and serum creatinine. Several programs used
      the USA's Kidney Early Evaluation Program's and International Society of
      Nephrology's templates. World Kidney Day activities contributed significantly.
      Stated needs were for more government recognition, firm policies and approaches,
      and critically, resources. Repeat responders reported progress in 2007,
      particularly in government interest and education delivery. Despite difficulties,
      programs are developing in many regions. Most need more resources and some
      members need substantial and sustained assistance.

PMID- 18813289
TI  - Cinacalcet suppresses calcification of the aorta and heart in uremic rats.
AB  - High serum parathyroid hormone levels are associated with vascular calcification.
      Cinacalcet is a calcimimetic agent that inhibits parathyroid hormone secretion
      and is used to treat patients with secondary hyperparathyroidism. Here we
      measured the effects of oral cinacalcet on calcification of the aorta and heart
      in rats with a remnant kidney (5/6 nephrectomy) model of uremia that were fed a
      high-phosphate diet containing lactose to accelerate the process of aortic
      calcification. Alizarin red staining showed that the smooth muscle in the aortic
      arch of rats with a remnant kidney was calcified. The tissue levels of calcium
      and phosphorus in the aorta and hearts of these rats were significantly increased
      compared to sham-operated rats. Expression of the osteoblastic lineage genes
      osteocalcin, osteopontin and runt-related gene 2 were also increased in the aorta
      of these rats. Cinacalcet suppressed these calcification-related changes by
      reducing serum parathyroid hormone, calcium, phosphorus, and the calcium
      phosphorus product. Parathyroidectomy also suppressed calcification in this
      model. We suggest that cinacalcet inhibits calcification of the aorta and heart
      in uremic patients with secondary hyperparathyroidism by decreasing serum
      parathyroid hormone levels.

PMID- 18813290
TI  - Podocyte foot process effacement as a diagnostic tool in focal segmental
      glomerulosclerosis.
AB  - Podocyte foot process effacement is characteristic of proteinuric renal diseases.
      In minimal change nephrotic syndrome (MCNS) foot processes are diffusely effaced
      whereas the extent of effacement varies in focal segmental glomerulosclerosis
      (FSGS). Here we measured foot process effacement in FSGS and compared it to that
      in MCNS and in normal kidneys. A clinical diagnosis was used to differentiate
      idiopathic FSGS from secondary FSGS. Median foot process width, determined
      morphometrically by electron microscopy, was 3236 nm in 17 patients with
      idiopathic FSGS, 1098 nm in 7 patients with secondary FSGS, and 1725 nm in 15
      patients with MCNS, as compared to 562 nm in 12 control patients. Multivariate
      analysis showed that foot process width did not correlate with proteinuria or
      serum albumin levels but was significantly associated as an independent factor
      with the type of disease. Foot process width over 1500 nm differentiated
      idiopathic from secondary FSGS with high sensitivity and specificity. Our results
      show that quantitative analysis of foot processes may offer a potential tool to
      distinguish idiopathic from secondary FSGS.

PMID- 18813291
TI  - Cyclin-dependent kinases and cell-cycle transitions: does one fit all?
AB  - Cell-cycle transitions in higher eukaryotes are regulated by different cyclin
      dependent kinases (CDKs) and their activating cyclin subunits. Based on
      pioneering findings that a dominant-negative mutation of CDK1 blocks the cell
      cycle at G2-M phase, whereas dominant-negative CDK2 inhibits the transition into
      S phase, a model of cell-cycle control has emerged in which each transition is
      regulated by a specific subset of CDKs and cyclins. Recent work with gene
      targeted mice has led to a revision of this model. We discuss cell-cycle control
      in light of overlapping and essential functions of the different CDKs and
      cyclins.

PMID- 18813292
TI  - The RSK family of kinases: emerging roles in cellular signalling.
AB  - The 90 kDa ribosomal S6 kinase (RSK) family of proteins is a group of highly
      conserved Ser/Thr kinases that regulate diverse cellular processes, such as cell
      growth, cell motility, cell survival and cell proliferation. RSKs are downstream
      effectors of the Ras-extracellular signal-regulated kinase (ERK)/mitogen
      activated protein kinase (MAPK) signalling cascade. Significant advances in the
      field of RSK and ERK/MAPK signalling have occurred in the past few years,
      including biological insights and the discovery of novel substrates and new RSK
      regulatory mechanisms. Collectively, these data expand the current models of RSK
      signalling and highlight potential directions of research in RSK-mediated
      survival, growth, proliferation and migration.

PMID- 18813293
TI  - Ataxia-telangiectasia: from a rare disorder to a paradigm for cell signalling and
      cancer.
AB  - First described over 80 years ago, ataxia-telangiectasia (A-T) was defined as a
      clinical entity 50 years ago. Although not encountered by most clinicians, it is
      a paradigm for cancer predisposition and neurodegenerative disorders and has a
      central role in our understanding of the DNA-damage response, signal transduction
      and cell-cycle control. The discovery of the protein A-T mutated (ATM) that is
      deficient in A-T paved the way for rapid progress on understanding how ATM
      functions with a host of other proteins to protect against genome instability and
      reduce the risk of cancer and other pathologies.

PMID- 18813295
TI  - Healthy by choice.
AB  - How can physical scientists contribute to biomedical applications and healthcare?

PMID- 18813294
TI  - Phagosome maturation: going through the acid test.
AB  - Phagosome maturation is the process by which internalized particles (such as
      bacteria and apoptotic cells) are trafficked into a series of increasingly
      acidified membrane-bound structures, leading to particle degradation. The
      characterization of the phagosomal proteome and studies in model organisms and
      mammals have led to the identification of numerous candidate proteins that
      cooperate to control the maturation of phagosomes containing different particles.
      A subset of these candidate proteins makes up the first pathway to be identified
      for the maturation of apoptotic cell-containing phagosomes. This suggests that a
      machinery that is distinct from receptor-mediated endocytosis is used in
      phagosome maturation.

PMID- 18813296
TI  - Nanomaterials at work in biomedical research.
AB  - With some nanomaterial-based medicines having entered the marketplace, and more
      on the verge of doing so, nanomedicine is expected to become an exciting
      playground for chemists and material scientists.

PMID- 18813297
TI  - The healthy option. Interview by Fabio Pulizzi.
AB  - Philips has recently changed its focus from electronic components to healthcare
      innovations. Nature Materials talked to Hans Hofstraat about the reasons behind
      this choice and how it affected Philips Research scientists.

PMID- 18813299
TI  - Electrochromic displays: The new black.

PMID- 18813300
TI  - Stimuli-responsive hydrogels: drugs take control.

PMID- 18813301
TI  - Particle transport: Salt and migrate.

PMID- 18813303
TI  - Energy: Fuel for thought.

PMID- 18813302
TI  - Oxygen catalysis: The other half of the equation.

PMID- 18813304
TI  - Material witness: Get knotted.

PMID- 18813306
TI  - Persisting depletion of brain glucose following cortical spreading depression,
      despite apparent hyperaemia: evidence for risk of an adverse effect of Leao's
      spreading depression.
AB  - Rapid sampling microdialysis (rsMD) directed towards the cerebral cortex has
      allowed identification of a combined time-series signature for glucose and
      lactate that characterizes peri-infarct depolarization in experimental focal
      ischaemia, but no comparable data exist for 'classical' cortical spreading
      depression (CSD) associated with hyperaemia in the normally perfused brain. Here,
      we examined the rsMD responses of dialysate glucose and lactate to five
      hyperaemic spreading depressions induced with intracortical microinjections,
      typically of 1 mol/L KCl, in open-skull preparations in five cats under
      chloralose anaesthesia. Depolarization was verified with microelectrodes, and
      laser speckle flowmetry was used to examine propagation of the events and
      perfusion responses near the MD probe. Ten minutes after depolarization,
      dialysate glucose fell and lactate rose by 28% and 58% respectively. There was no
      recovery of dialysate glucose 30 mins after depolarization. Mean baseline
      indicative cerebral blood flow was 25.5+/-4.1 mL/100 g/min and mean maximum
      hyperaemic increase was by 29.6+/-6 mL/100 g/min; hyperaemia remained present 30
      mins after CSD. As CSD events are repetitive, frequent, and often clustered
      temporally in human acute brain injury, these results indicate a high risk of
      depletion of extracellular glucose in association with depolarization events of a
      pattern previously thought to be largely benign.

PMID- 18813307
TI  - Breast cancer awareness among older women.
AB  - The aim of this study was to elicit the level of breast cancer awareness in older
      women. A cross-sectional study-specific questionnaire survey of 712 British women
      aged 67-73 years (response rate 83.8%), assessing knowledge of symptoms and risk
      and confidence to detect a change, was conducted. Over 85% of respondents were
      aware that a lump was a symptom of breast cancer but knowledge of non-lump
      symptoms was limited. Knowledge of risk was poor; 50% believed that the lifetime
      risk of developing breast cancer was less than 1 in 100 women and 75% were not
      aware that age is a risk factor. Thirty-one percent of women reported low levels
      of confidence to detect a breast change and 19% rarely or never checked their
      breasts. Those with fewer educational qualifications had poorer knowledge of
      symptoms, less awareness of lifetime and age-related risks, but were more likely
      to check their breasts than more highly educated women. This national survey
      demonstrates a significant lack of the prerequisite knowledge and confidence to
      detect a breast change. Raising breast cancer awareness and promoting early
      presentation among older women is important, as they are more at risk of breast
      cancer and more likely to delay seeking help with breast cancer symptoms than
      younger women.

PMID- 18813308
TI  - High expression of TROP2 correlates with poor prognosis in pancreatic cancer.
AB  - Pancreatic cancer is one of the most devastating human malignancies. Despite
      considerable research efforts, it remains resistant to almost all available
      treatment regimens. The human trophoblast cell-surface antigen, TROP2, was found
      to be strongly expressed in a variety of human epithelial cancers, correlating
      with aggressiveness and poor prognosis. TROP2 antigen expression was investigated
      retrospectively by immunohistochemistry in paraffin-embedded primary tumour
      tissue samples from a series (n=197) of consecutive patients with pancreatic
      adenocarcinoma. Survival was calculated using Kaplan-Meier curves. Parameters
      found to be of prognostic significance in univariate analysis were verified in a
      multivariate Cox regression model. TROP2 overexpression was observed in 109 (55%)
      of 197 pancreatic cancer patients and was significantly associated with decreased
      overall survival (P<0.01). By univariate analysis, TROP2 overexpression was found
      to correlate with the presence of lymph node metastasis (P=0.04) and tumour grade
      (P=0.01). Furthermore, in the subgroup of patients treated surgically with
      curative intent, TROP2 overexpression significantly correlated with poor
      progression-free survival (P<0.01). Multivariate analyses revealed TROP2 to be an
      independent prognosticator. These findings suggest for the first time that TROP2
      could be a novel prognostic biomarker for pancreatic cancer. Targeting TROP2
      might be a useful treatment approach for patients with pancreatic cancer
      overexpressing this cell-surface marker.

PMID- 18813309
TI  - Prospective study of dietary patterns and colorectal cancer among Singapore
      Chinese.
AB  - An influence of Western diet and lifestyle factors observed among Singapore
      Chinese may contribute to the population's marked rise in colorectal cancer
      incidence over the past two decades. Thus far, however, there is little evidence
      for individual nutrients and foods as major contributing factors in this
      population. We evaluated whether patterns of food intake were associated with
      colorectal cancer in a population-based cohort of 61,321 Singapore Chinese that
      was established in 1993-98. Two dietary patterns, meat-dim sum and vegetable
      fruit-soy, were previously identified by principal components analysis using
      baseline dietary data from a validated 165-item food frequency questionnaire. As
      of 31 December 2005, 961 incident colorectal cancer cases were diagnosed.
      Proportional hazards regression was used to calculate adjusted hazard ratios.
      Using nearly 10 years of follow-up data, we observed no association with either
      the meat-dim sum or vegetable-fruit-soy pattern for colorectal cancer. In
      conclusion, neither individual nutrients or foods nor dietary patterns appear to
      explain the rise in colorectal cancer among Singapore Chinese population.

PMID- 18813310
TI  - Hypoxia upregulates expression of human endosialin gene via hypoxia-inducible
      factor 2.
AB  - Endosialin is a transmembrane glycoprotein selectively expressed in blood vessels
      and stromal fibroblasts of various human tumours. It has been functionally
      implicated in angiogenesis, but the factors that control its expression have
      remained unclear. As insufficient delivery of oxygen is a driving force of
      angiogenesis in growing tumours, we investigated whether hypoxia regulates
      endosialin expression. Here, we demonstrate that endosialin gene transcription is
      induced by hypoxia predominantly through a mechanism involving hypoxia-inducible
      factor-2 (HIF-2) cooperating with the Ets-1 transcription factor. We show that
      HIF-2 activates the endosialin promoter both directly, through binding to a
      hypoxia-response element adjacent to an Ets-binding site in the distal part of
      the upstream regulatory region, and indirectly, through Ets-1 and its two cognate
      elements in the proximal promoter. Our data also suggest that the SP1
      transcription factor mediates responsiveness of the endosialin promoter to high
      cell density. These findings elucidate important aspects of endosialin gene
      regulation and provide a rational frame for future investigations towards better
      understanding of its biological significance.

PMID- 18813311
TI  - Coffee intake and CYP1A2*1F genotype predict breast volume in young women:
      implications for breast cancer.
AB  - As breast volume may be associated with heart cancer risk, we studied the
      relationship between breast volume, CYP1A2*1F and coffee intake. Among healthy
      premenopausal non-hormone users, 3+ cups per day was associated with lower volume
      only in C-allele carriers (P(interaction)=0.02), which is consistent with reports
      that coffee protects only C-allele carriers against breast cancer.

PMID- 18813312
TI  - Endometrial stromal sarcoma: a population-based analysis.
AB  - To determine independent prognostic factors for the survival of patients with
      endometrial stromal sarcoma (ESS), data were abstracted from the Surveillance,
      Epidemiology, and End Results (SEER) database of the National Cancer Institute
      from 1988 to 2003. Kaplan-Meier and Cox proportional hazards models were used for
      analyses. Of 831 women diagnosed with ESS, the median age was 52 years (range: 17
      96 years). In total, 59.9% had stage I, 5.1% stage II, 14.9% stage III, and 20.1%
      had stage IV disease. Overall, 13.0, 36.1, and 34.7% presented with grades 1, 2,
      and 3, respectively. Patients with stage I-II vs III-IV disease had 5 years DSS
      of 89.3% vs 50.3% (P<0.001) and those with grades 1, 2, and 3 cancers had
      survivals of 91.4, 95.4, and 42.1% (P<0.001). In multivariate analysis, older
      patients, black race, advanced stage, higher grade, lack of primary surgery, and
      nodal metastasis were independent prognostic factors for poorer survival. In
      younger women (<50 years) with stage I-II disease, ovarian-sparing procedures did
      not adversely impact survival (91.9 vs 96.2%; P=0.1). Age, race, primary surgery,
      stage, and grade are important prognostic factors for ESS. Excellent survival in
      patients with grade 1 and 2 disease of all stages supports the concept that these
      tumors are significantly different from grade 3 tumors. Ovarian-sparing surgeries
      may be considered in younger patients with early-stage disease.

PMID- 18813313
TI  - Sleep duration and the risk of breast cancer: the Ohsaki Cohort Study.
AB  - In a prospective study of 23 995 Japanese women, short sleep duration was
      associated with higher risk of breast cancer (143 cases), compared with women who
      slept 7 h per day, the multivariate hazard ratio of those who slept </=6 h per
      day was 1.62 (95% confidence interval: 1.05-2.50; P for trend=0.03).

PMID- 18813314
TI  - Use of photosensitising diuretics and risk of skin cancer: a population-based
      case-control study.
AB  - Diuretics have photosensitising properties. However, little is known about how
      these diuretics affect the risk of skin cancers. In North Jutland County,
      Denmark, we investigated whether the use of photosensitising diuretics was
      associated with an increased risk for developing basal cell carcinoma (BCC),
      squamous cell carcinoma (SCC) and malignant melanoma (MM). From the cancer
      registry, we identified primary cases of BCC, SCC and MM during the period of
      1989-2003. We selected four population controls for each case from the Danish
      Civil Registration System, matched on age and gender. Prescriptions for
      photosensitising diuretics before cancer diagnosis were ascertained in the
      county's Prescription Database. We used conditional logistic regression to
      compute incidence rate ratio (IRR), controlling for the chronic medical
      conditions and for the previous use of oral glucocorticoids. We found an
      increased risk of SCC (IRR of 1.79 (95% confidence interval (CI): 1.45-2.21)) and
      MM (IRR of 1.43 (95% CI: 1.09-1.88)) among users of combined amiloride and
      hydrochlorothiazide therapy. An increased risk of MM (IRR of 3.30 (95% CI: 1.34
      8.10)) was found among users of indapamide. We found little associations with
      risk of BCC. Our findings provide evidence that the use of some photosensitising
      diuretics is associated with an increased risk for SCC and MM.

PMID- 18813315
TI  - A novel AKT3 mutation in melanoma tumours and cell lines.
AB  - Recently, a rare activating mutation of AKT1 (E17K) has been reported in breast,
      ovarian, and colorectal cancers. However, analogous activating mutations in AKT2
      or AKT3 have not been identified in any cancer lineage. To determine the
      prevalence of AKT E17K mutations in melanoma, the most aggressive form of skin
      cancer, we analysed 137 human melanoma specimens and 65 human melanoma cell lines
      for the previously described activating mutation of AKT1, and for analogous
      mutations in AKT2 and AKT3. We identified a single AKT1 E17K mutation.
      Remarkably, a previously unidentified AKT3 E17K mutation was detected in two
      melanomas (from one patient) as well as two cell lines. The AKT3 E17K mutation
      results in activation of AKT when expressed in human melanoma cells. This
      represents the first report of AKT mutations in melanoma, and the initial
      identification of an AKT3 mutation in any human cancer lineage. We have also
      identified the first known human cell lines with naturally occurring AKT E17K
      mutations.

PMID- 18813316
TI  - The ASGT and ethical codes for clinical research.

PMID- 18813321
TI  - The TRAIL apoptotic pathway in cancer onset, progression and therapy.
AB  - Triggering of tumour cell apoptosis is the foundation of many cancer therapies.
      Death receptors of the tumour necrosis factor (TNF) superfamily have been largely
      characterized, as have the signals that are generated when these receptors are
      activated. TNF-related apoptosis-inducing ligand (TRAIL) receptors (TRAILR1 and
      TRAILR2) are promising targets for cancer therapy. Herein we review what is known
      about the molecular control of TRAIL-mediated apoptosis, the role of TRAIL in
      carcinogenesis and the potential therapeutic utility of recombinant TRAIL and
      agonistic antibodies against TRAILR1 and TRAILR2.

PMID- 18813322
TI  - Towards a hybrid model for the cryopreservation of umbilical cord blood stem
      cells.

PMID- 18813320
TI  - Basal cell carcinomas: attack of the hedgehog.
AB  - Basal cell carcinomas (BCCs) were essentially a molecular 'black box' until some
      12 years ago, when identification of a genetic flaw in a rare subset of patients
      who have a great propensity to develop BCCs pointed to aberrant Hedgehog
      signalling as the pivotal defect leading to formation of these tumours. This
      discovery has facilitated a remarkable increase in our understanding of BCC
      carcinogenesis and has highlighted the carcinogenic role of this developmental
      pathway when aberrantly activated in adulthood. Importantly, a phase 1 first-in
      human trial of a Hedgehog inhibitor has shown real progress in halting and even
      reversing the growth of these tumours.

PMID- 18813324
TI  - Cord blood stem cells: worth the investment.

PMID- 18813325
TI  - Opinions regarding cord blood use need an update.

PMID- 18813326
TI  - Speciation with gene flow in the large white-headed gulls: does selection
      counterbalance introgression?
AB  - We investigated the role of selection in generating and maintaining species
      distinctness in spite of ongoing gene flow, using two zones of secondary contact
      between large gull species in Europe (Larus argentatus and Larus cachinnans) and
      North America (Larus glaucescens and Larus occidentalis). We used the pattern of
      neutral genetic differentiation at nine microsatellite loci (F(ST)) as an
      indicator of expected changes under neutral processes and compared it with
      phenotypic differentiation (P(ST)) for a large number of traits (size, plumage
      melanism and coloration of bare parts). Even assuming very low heritability,
      interspecific divergence between L. glaucescens and L. occidentalis in plumage
      melanism and orbital ring colour clearly exceeded neutral differentiation.
      Similarly, melanism of the central primaries was highly divergent between L.
      argentatus and L. cachinnans. Such divergence is unlikely to have arisen randomly
      and is therefore attributed to spatially varying selection. Variation in plumage
      melanism in both transects agrees with Gloger's rule, which suggests that
      latitude (and associated sun and humidity gradients) could be the selective
      pressure shaping differentiation in plumage melanism. We suggest that strong
      species differentiation in orbital ring colour results from sexual selection. We
      conclude that these large gull species, along with other recently diverged
      species that hybridize after coming into secondary contact, may differ only in
      restricted regions of the genome that are undergoing strong disruptive selection
      because of their phenotypic effects.

PMID- 18813327
TI  - Effects of seed- and pollen-mediated gene dispersal on genetic structure among
      Quercus salicina saplings.
AB  - We evaluated the effects of seed- and pollen-mediated gene dispersal on genetic
      structure among Quercus salicina saplings. Parentage analysis using 10
      microsatellite markers indicated that the 111 adult trees located within a 11.56
      ha plot in the Tatera Forest Reserve, Japan, included only one parent of 44.2%
      and both parents of 40.7% of the 226 saplings located in a 1-ha core plot at its
      center. Coancestry (F(ij)) estimates indicated that there was strong genetic
      structure among the saplings. The numbers of pairs of full- and half-siblings
      were high among neighboring saplings, suggesting that there was strong maternal
      half-sibling family structure among the saplings around their seed parents,
      probably generated by the spatially limited seed dispersal and the small extent
      of overlapping seed shadows owing to the low density of adults. The frequencies
      also suggest that the maternal half-sibling families are interspersed with full
      siblings, produced by correlated mating, probably because pollination frequency
      depends on the distance between parents. The frequencies of pairs of half
      siblings decreased as the distance between saplings increased, but did not fall
      to zero even at distances up to the 90-95 m class, suggesting that paternal half
      siblings originating from correlated paternity were widely distributed owing to
      extensive pollen flow. We separately examined the genetic structure for maternal
      and paternal alleles in the saplings. Unsurprisingly, very strong genetic
      structure was detected for maternal alleles. However, weak (but significant)
      genetic structure was also detected for paternal alleles. Therefore, pollen
      dispersal may affect the extent of genetic structure as well as seed dispersal.

PMID- 18813328
TI  - The role of linkage disequilibrium in the evolution of premating isolation.
AB  - The suggestion that speciation may often occur, or be completed, in the presence
      of gene flow has long been contentious, due to an appreciation of the challenges
      to maintaining population- or species-specific gene combinations when gene flow
      is occurring. Linkage disequilibrium between loci involved in postzygotic and
      premating isolation must often be built and maintained as the source of these
      species-specific genotypes. Here, I discuss proposed solutions to facilitate the
      establishment and maintenance of this linkage disequilibrium. I concentrate
      primarily on two such factors: one-allele versus two-allele mechanisms of
      premating isolation, and the form of selection against hybrids as it relates to
      its effect on the pathway between postzygotic and prezygotic isolation. The goal
      of this discussion is not to thoroughly review these factors, but instead to
      concentrate on aspects and implications of these solutions that are currently
      underemphasized in the speciation literature.

PMID- 18813329
TI  - Re: High concordance between immunohistochemistry and fluorescence in situ
      hybridization testing for HER2 status in breast cancer requires a normalized IHC
      scoring system.

PMID- 18813331
TI  - Variations in HSP70 genes associated with noise-induced hearing loss in two
      independent populations.
AB  - Noise-induced hearing loss (NIHL) is one of the most important occupational
      health hazards. Millions of people worldwide are exposed daily to harmful levels
      of noise. NIHL is a complex disease resulting from an interaction between genetic
      and environmental factors. Although the environmental risk factors have been
      studied extensively, little is known about the genetic factors. Heat-shock
      proteins (HSPs) are induced after exposure to severe noise. When first induced by
      exposure to moderate sound levels, they can protect the ear from damage from
      excessive noise exposure. This protection is highly variable between individuals.
      An association of HSP70 genes with NIHL has been described by Yang et al (2006)
      in a Chinese sample set of noise-exposed workers. In this study, three
      polymorphisms (rs1043618, rs1061581 and rs2227956) in HSP70-1, HSP70-2 and HSP70
      hom, respectively, were genotyped in 206 Swedish and 238 Polish DNA samples of
      noise-exposed subjects and analyzed. One SNP, rs2227956 in HSP70-hom, resulted in
      a significant association with NIHL in both sample sets. In addition, rs1043618
      and rs1061581 were significant in the Swedish sample set. Analysis of the
      haplotypes composed of the three SNPs revealed significant associations between
      NIHL and haplotype GAC in both sample sets and with haplotype CGT in the Swedish
      sample set. In conclusion, this study replicated the association of HSP70 genes
      with NIHL in a second and third independent noise-exposed sample set, hereby
      adding to the evidence that HSP70 genes may be NIHL susceptibility genes.

PMID- 18813332
TI  - A familial inverted duplication/deletion of 2p25.1-25.3 provides new clues on the
      genesis of inverted duplications.
AB  - We studied a family in which the same 10 Mb inverted duplication of 2p25.3-p25.1
      segregates in two children and their father, all showing a trisomy phenotype. As
      FISH analysis demonstrated that the duplication was inverted, we suspected that a
      contiguous terminal deletion was also present, according to the classical inv dup
      del type of rearrangements. Although FISH with 2p and 2q subtelomeric probes gave
      normal results, 100 kb resolution array-C/GH (aCGH) showed that, beside the
      duplication, a 273 kb deletion was also present. The presence of a single-copy
      region between the deleted and duplicated regions was further suspected through
      high-resolution aCGH analysis (approximately 20 kb), although only one
      informative spot having a normal log ratio was detected. The precise structure of
      the rearrangement was re-defined by real-time PCR and breakpoint cloning,
      demonstrating the presence of a 2680 bp single-copy sequence between deleted and
      duplicated regions and the involvement of a simple repeat with the potential for
      forming a non-B DNA structure. The rearrangement was not mediated by segmental
      duplications or short inverted repeats, and the double-strand break might have
      been repaired by non-homologous end joining or microhomology-mediated intrastrand
      repair. These data highlight the fact that concomitant deletions associated with
      inverted duplications are very likely to be more frequent than classical
      cytogenetic methods alone have been able to demonstrate. The phenotypic effects
      of the trisomy and of the terminal 2p deletion are discussed.

PMID- 18813333
TI  - Molecular genetics of arrhythmogenic right ventricular dysplasia/cardiomyopathy.

PMID- 18813335
TI  - Cardiovascular disease and the UN Millennium Development Goals: time to move
      forward.

PMID- 18813336
TI  - Changes in the gender and ethnic balance of the United Kingdom orthodontic
      workforce.
AB  - OBJECTIVE: To describe the gender and ethnic trends of the United Kingdom
      orthodontic workforce. DESIGN AND SETTING: A cross-sectional survey using a
      postal questionnaire to specialist orthodontic practitioners in the United
      Kingdom (2006-2007).Subjects All those on the Specialist List in Orthodontics
      held by the General Dental Council in October 2006. MATERIALS AND METHODS: The
      data collected using the questionnaire included demographic details (gender,
      ethnicity, current age, place of birth), undergraduate and postgraduate dental
      schools attended, calendar years in which professional qualifications were
      achieved, anticipated year of retirement and geographical location of work place.
      RESULTS: The response rate was 81.5%. There are more male (60.2%) than female
      (39.8%) orthodontists presently working in the United Kingdom. Minority ethnic
      groups are better represented amongst the orthodontic workforce than they are in
      the general population, however their distribution throughout the United Kingdom
      is uneven. The trends in the results indicate that the gender and ethnic balance
      of the specialist orthodontic workforce has been changing and the proportion of
      females and those from non-white ethnic groups has increased. In contrast, the
      majority of those retiring over the next few years will be white males (60%).
      CONCLUSION: This study suggests that there will be greater ethnic diversity and
      more female orthodontists in the future workforce. Consequently, working patterns
      should be kept under regular review so that an optimal orthodontic service can be
      maintained in the United Kingdom.

PMID- 18813337
TI  - Glass transition temperature prediction of polymers through the mass-per-flexible
      bond principle.
AB  - A semi-empirical method based on the mass-per-flexible-bond (M/f) principle was
      used to quantitatively explain the large range of glass transition temperatures
      (T(g)) observed in a library of 132 L-tyrosine derived homo, co- and terpolymers
      containing different functional groups. Polymer class specific behavior was
      observed in T(g) vs. M/f plots, and explained in terms of different densities,
      steric hindrances and intermolecular interactions of chemically distinct
      polymers. The method was found to be useful in the prediction of polymer T(g).
      The predictive accuracy was found to range from 6.4 to 3.7 K, depending on
      polymer class. This level of accuracy compares favorably with (more complicated)
      methods used in the literature. The proposed method can also be used for
      structure prediction of polymers to match a target T(g) value, by keeping the
      thermal behavior of a terpolymer constant while independently choosing its
      chemistry. Both applications of the method are likely to have broad applications
      in polymer and (bio)material science.

PMID- 18813338
TI  - Some rare Indo-Pacific coral species are probable hybrids.
AB  - BACKGROUND: Coral reefs worldwide face a variety of threats and many coral
      species are increasingly endangered. It is often assumed that rare coral species
      face higher risks of extinction because they have very small effective population
      sizes, a predicted consequence of which is decreased genetic diversity and
      adaptive potential. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that some Indo
      Pacific members of the coral genus Acropora have very small global population
      sizes and are likely to be unidirectional hybrids. Whether this reflects hybrid
      origins or secondary hybridization following speciation is unclear.
      CONCLUSIONS/SIGNIFICANCE: The interspecific gene flow demonstrated here implies
      increased genetic diversity and adaptive potential in these coral species. Rare
      Acropora species may therefore be less vulnerable to extinction than has often
      been assumed because of their propensity for hybridization and introgression,
      which may increase their adaptive potential.

PMID- 18813339
TI  - Proteolysis of proBDNF is a key regulator in the formation of memory.
AB  - It is essential to understand the molecular processes underlying long-term memory
      to provide therapeutic targets of aberrant memory that produce pathological
      behaviour in humans. Under conditions of recall, fully-consolidated memories can
      undergo reconsolidation or extinction. These retrieval-mediated memory processes
      may rely on distinct molecular processes. The cellular mechanisms initiating the
      signature molecular events are not known. Using infusions of protein synthesis
      inhibitors, antisense oligonucleotide targeting brain-derived neurotrophic factor
      (BDNF) mRNA or tPA-STOP (an inhibitor of the proteolysis of BDNF protein) into
      the hippocampus of the awake rat, we show that acquisition and extinction of
      contextual fear memory depended on the increased and decreased proteolysis of
      proBDNF (precursor BDNF) in the hippocampus, respectively. Conditions of
      retrieval that are known to initiate the reconsolidation of contextual fear
      memory, a BDNF-independent memory process, were not correlated with altered
      proBDNF cleavage. Thus, the processing of BDNF was associated with the
      acquisition of new information and the updating of information about a salient
      stimulus. Furthermore, the differential requirement for the processing of proBDNF
      by tPA in distinct memory processes suggest that the molecular events actively
      engaged to support the storage and/or the successful retrieval of memory depends
      on the integration of ongoing experience with past learning.

PMID- 18813340
TI  - Bacterial disease and antimicrobial susceptibility patterns in HIV-infected,
      hospitalized children: a retrospective cohort study.
AB  - BACKGROUND: Serious bacterial infections are a major source of morbidity and
      mortality in HIV-infected children. The spectrum of disease is wide, and
      responsible organisms vary according to setting. The use of antibiotic
      prophylaxis and the emergence of multi-drug resistant bacteria necessitate
      examination of responsible organisms and their antibiotic susceptibility.
      METHODOLOGY/PRINCIPAL FINDINGS: A retrospective cohort study of all HIV-positive
      pediatric admissions at an urban public sector hospital in Cape Town between
      January 2002 and June 2006 was conducted. Children between the ages of one month
      and nine years with laboratory confirmed HIV status, serious bacterial infection,
      and a hospital length of stay of 5 days or more, were eligible for inclusion.
      Organisms isolated from blood, urine, and cerebral spinal fluid cultures and
      their antimicrobial susceptibility were examined, and compared according to
      timing of isolation to distinguish nosocomial versus community-acquired. One
      hundred and forty-one children were identified (median age 1.2 years), 39% of
      whom were on antiretrovirals started before or during this hospitalization.
      Bacterial infections involved all organ systems, however pneumonia was most
      common (67%). S. pneumoniae and S. aureus were the most common gram positive and
      K. pneumoniae was the most common gram negative organism. K pneumoniae isolates
      were resistant to many first and second line antibiotics, and were all considered
      nosocomial. All S. aureus isolates were methicillin resistant, some of which were
      community-acquired. CONCLUSIONS/SIGNIFICANCE: Bacterial infections are an
      important source of co-morbidity in HIV-infected children in resource-limited
      settings. Clinicians should have a low threshold to initiate antibiotics in
      children requiring hospitalization. Broad-spectrum antibiotics should be used
      judiciously. Clinicians caring for HIV-infected children should be cognizant of
      the most common organisms affecting such children, and of their local
      antimicrobial susceptibilities, when treating empirically for serious bacterial
      infections.

PMID- 18813341
TI  - Activin A induces Langerhans cell differentiation in vitro and in human skin
      explants.
AB  - Langerhans cells (LC) represent a well characterized subset of dendritic cells
      located in the epidermis of skin and mucosae. In vivo, they originate from
      resident and blood-borne precursors in the presence of keratinocyte-derived
      TGFbeta. In vitro, LC can be generated from monocytes in the presence of GM-CSF,
      IL-4 and TGFbeta. However, the signals that induce LC during an inflammatory
      reaction are not fully investigated. Here we report that Activin A, a TGFbeta
      family member induced by pro-inflammatory cytokines and involved in skin
      morphogenesis and wound healing, induces the differentiation of human monocytes
      into LC in the absence of TGFbeta. Activin A-induced LC are Langerin+, Birbeck
      granules+, E-cadherin+, CLA+ and CCR6+ and possess typical APC functions. In
      human skin explants, intradermal injection of Activin A increased the number of
      CD1a+ and Langerin+ cells in both the epidermis and dermis by promoting the
      differentiation of resident precursor cells. High levels of Activin A were
      present in the upper epidermal layers and in the dermis of Lichen Planus biopsies
      in association with a marked infiltration of CD1a+ and Langerin+ cells. This
      study reports that Activin A induces the differentiation of circulating CD14+
      cells into LC. Since Activin A is abundantly produced during inflammatory
      conditions which are also characterized by increased numbers of LC, we propose
      that this cytokine represents a new pathway, alternative to TGFbeta, responsible
      for LC differentiation during inflammatory/autoimmune conditions.

PMID- 18813342
TI  - Protein microarray on-demand: a novel protein microarray system.
AB  - We describe a novel, simple and low-cost protein microarray strategy wherein the
      microarrays are generated by printing expression ready plasmid DNAs onto slides
      that can be converted into protein arrays on-demand. The printed expression
      plasmids serve dual purposes as they not only direct the synthesis of the protein
      of interest; they also serve to capture the newly synthesized proteins through a
      high affinity DNA-protein interaction. To accomplish this we have exploited the
      high-affinity binding (approximately 3-7 x 10 (-13) M) of E. coli Tus protein to
      Ter, a 20 bp DNA sequence involved in the regulation of E. coli DNA replication.
      In our system, each protein of interest is synthesized as a Tus fusion protein
      and each expression construct directing the protein synthesis contains embedded
      Ter DNA sequence. The embedded Ter sequence functions as a capture reagent for
      the newly synthesized Tus fusion protein. This "all DNA" microarray can be
      converted to a protein microarray on-demand without need for any additional
      capture reagent.

PMID- 18813343
TI  - Frontal white matter anisotropy and antidepressant remission in late-life
      depression.
AB  - INTRODUCTION: Neuroanatomic features associated with antidepressant treatment
      outcomes in older depressed individuals are not well established. This study used
      diffusion tensor imaging to examine frontal white matter structure in depressed
      subjects undergoing a 12-week trial of sertraline. We hypothesized that remission
      would be associated with higher frontal anisotropy measures, and failure to remit
      with lower anisotropy. METHODS: 74 subjects with Major Depressive Disorder and
      age 60 years or older were enrolled in a twelve-week open-label trial of
      sertraline and completed clinical assessments and 1.5T magnetic resonance brain
      imaging. The apparent diffusion coefficient (ADC) and fractional anisotropy (FA)
      were measured in regions of interest placed in the white matter of the
      dorsolateral prefrontal cortex, anterior cingulate cortex, and corpus callosum.
      Differences in ADC and FA values between subjects who did and did not remit to
      treatment over the study period were assessed using generalized estimating
      equations, controlling for age, sex, medical comorbidity and baseline depression
      severity. RESULTS: Subjects who did not remit to sertraline exhibited higher FA
      values in the superior frontal gyri and anterior cingulate cortices bilaterally.
      There were no statistically significant associations between ADC measures and
      remission. CONCLUSIONS: Failure to remit to sertraline is associated with higher
      frontal FA values. Functional imaging studies demonstrate that depression is
      characterized by functional disconnection between frontal and limbic regions.
      Those individuals where this disconnection is related to structural changes as
      detected by DTI may be more likely to respond to antidepressants. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT00339066.

PMID- 18813344
TI  - On evaluating MHC-II binding peptide prediction methods.
AB  - Choice of one method over another for MHC-II binding peptide prediction is
      typically based on published reports of their estimated performance on standard
      benchmark datasets. We show that several standard benchmark datasets of unique
      peptides used in such studies contain a substantial number of peptides that share
      a high degree of sequence identity with one or more other peptide sequences in
      the same dataset. Thus, in a standard cross-validation setup, the test set and
      the training set are likely to contain sequences that share a high degree of
      sequence identity with each other, leading to overly optimistic estimates of
      performance. Hence, to more rigorously assess the relative performance of
      different prediction methods, we explore the use of similarity-reduced datasets.
      We introduce three similarity-reduced MHC-II benchmark datasets derived from
      MHCPEP, MHCBN, and IEDB databases. The results of our comparison of the
      performance of three MHC-II binding peptide prediction methods estimated using
      datasets of unique peptides with that obtained using their similarity-reduced
      counterparts shows that the former can be rather optimistic relative to the
      performance of the same methods on similarity-reduced counterparts of the same
      datasets. Furthermore, our results demonstrate that conclusions regarding the
      superiority of one method over another drawn on the basis of performance
      estimates obtained using commonly used datasets of unique peptides are often
      contradicted by the observed performance of the methods on the similarity-reduced
      versions of the same datasets. These results underscore the importance of using
      similarity-reduced datasets in rigorously comparing the performance of
      alternative MHC-II peptide prediction methods.

PMID- 18813345
TI  - Modulating attentional load affects numerosity estimation: evidence against a pre
      attentive subitizing mechanism.
AB  - Traditionally, the visual enumeration of a small number of items (1 to about 4),
      referred to as subitizing, has been thought of as a parallel and pre-attentive
      process and functionally different from the serial attentive enumeration of
      larger numerosities. We tested this hypothesis by employing a dual task paradigm
      that systematically manipulated the attentional resources available to an
      enumeration task. Enumeration accuracy for small numerosities was severely
      decreased as more attentional resources were taken away from the numerical task,
      challenging the traditionally held notion of subitizing as a pre-attentive,
      capacity-independent process. Judgement of larger numerosities was also affected
      by dual task conditions and attentional load. These results challenge the
      proposal that small numerosities are enumerated by a mechanism separate from
      large numerosities and support the idea of a single, attention-demanding
      enumeration mechanism.

PMID- 18813346
TI  - Analysis of the Pseudoalteromonas tunicata genome reveals properties of a surface
      associated life style in the marine environment.
AB  - BACKGROUND: Colonisation of sessile eukaryotic host surfaces (e.g. invertebrates
      and seaweeds) by bacteria is common in the marine environment and is expected to
      create significant inter-species competition and other interactions. The
      bacterium Pseudoalteromonas tunicata is a successful competitor on marine
      surfaces owing primarily to its ability to produce a number of inhibitory
      molecules. As such P. tunicata has become a model organism for the studies into
      processes of surface colonisation and eukaryotic host-bacteria interactions.
      METHODOLOGY/PRINCIPAL FINDINGS: To gain a broader understanding into the
      adaptation to a surface-associated life-style, we have sequenced and analysed the
      genome of P. tunicata and compared it to the genomes of closely related strains.
      We found that the P. tunicata genome contains several genes and gene clusters
      that are involved in the production of inhibitory compounds against surface
      competitors and secondary colonisers. Features of P. tunicata's oxidative stress
      response, iron scavenging and nutrient acquisition show that the organism is well
      adapted to high-density communities on surfaces. Variation of the P. tunicata
      genome is suggested by several landmarks of genetic rearrangements and mobile
      genetic elements (e.g. transposons, CRISPRs, phage). Surface attachment is likely
      to be mediated by curli, novel pili, a number of extracellular polymers and
      potentially other unexpected cell surface proteins. The P. tunicata genome also
      shows a utilisation pattern of extracellular polymers that would avoid a
      degradation of its recognised hosts, while potentially causing detrimental
      effects on other host types. In addition, the prevalence of recognised virulence
      genes suggests that P. tunicata has the potential for pathogenic interactions.
      CONCLUSIONS/SIGNIFICANCE: The genome analysis has revealed several physiological
      features that would provide P. tunciata with competitive advantage against other
      members of the surface-associated community. We have also identified properties
      that could mediate interactions with surfaces other than its currently recognised
      hosts. This together with the detection of known virulence genes leads to the
      hypothesis that P. tunicata maintains a carefully regulated balance between
      beneficial and detrimental interactions with a range of host surfaces.

PMID- 18813347
TI  - Decoy receptor 3 is a prognostic factor in renal cell cancer.
AB  - BACKGROUND: Decoy receptor 3 (DcR3) is a soluble protein that binds to and
      inactivates the death ligand CD95L. Here, we studied a possible association
      between DcR3 expression and prognosis in patients with renal cell carcinomas
      (RCCs). METHODS: A tissue microarray containing RCC tumor tissue samples and
      corresponding normal tissue samples was generated. Decoy receptor 3 expression in
      tumors of 560 patients was examined by immunohistochemistry. The effect of DcR3
      expression on disease-specific survival and progression-free survival was
      assessed using univariate analysis and multivariate Cox regression analysis.
      Decoy receptor 3 serum levels were determined by ELISA. FINDINGS: High DcR3
      expression was associated with high-grade (P = .005) and high-stage (P = .048)
      RCCs. The incidence of distant metastasis (P = .03) and lymph node metastasis (P
      = .002) was significantly higher in the group with high DcR3 expression. Decoy
      receptor 3 expression correlated negatively with disease-specific survival (P <
      .001) and progression-free survival (P < .001) in univariate analyses. A
      multivariate Cox regression analysis retained DcR3 expression as an independent
      prognostic factor that outperformed the Karnofsky performance status. In patients
      with high-stage RCCs expressing DcR3, the 2-year survival probability was 25%,
      whereas in patients with DcR3-negative tumors, the survival probability was 65%
      (P < .001). Moreover, DcR3 serum levels were significantly higher in patients
      with high-stage localized disease (P = .007) and metastatic disease (P = .001).
      INTERPRETATION: DcR3 expression is an independent prognostic factor of RCC
      progression and mortality. Therefore, the assessment of DcR3 expression levels
      offers valuable prognostic information that could be used to select patients for
      adjuvant therapy studies.

PMID- 18813348
TI  - Hsf1 is required for the nuclear translocation of p53 tumor suppressor.
AB  - Although the p53 tumor suppressor is most frequently inactivated by genetic
      mutations, exclusion from the nucleus is also seen in human tumors. We have begun
      to examine p53 nuclear importation by isolating a series of mutant cells in which
      the temperature-sensitive murine p53(Val135) mutant is sequestered in the
      cytoplasm. We previously showed that that three of them (ALTR12, ALTR19, and
      ALTR25) constituted a single complementation group. Here, we found that ALTR12
      cells are more sensitive to heat stress than either ALTR19 or ALTR25 and that
      there was a complete lack of induction of Hsp70 in response to heat shock.
      Western blot analysis showed no expression of the Hsf1 transcription factor, and
      neither heat shock nor azetidine could induce p53 nuclear localization in ALTR12
      cells but did in parental A1-5 cells. Suppression of Hsf1 in A1-5 cells with
      quercetin or an Hsf1 siRNA reduced p53 nuclear importation and inhibited p53
      mediated activation of a p21 reporter. Most convincingly, p53 nuclear importation
      could be restored in ALTR12 cells by introducing an exogenous Hsf1 gene.
      Collectively, our result suggests that Hsf1 is required for p53 nuclear
      importation and activation and implies that heat shock factors play a role in the
      regulation of p53.

PMID- 18813349
TI  - SPARC ameliorates ovarian cancer-associated inflammation.
AB  - We have recently identified that the role of secreted protein acidic and rich in
      cysteine (SPARC) in amelioration of peritoneal ovarian carcinomatosis is
      mediated, at least in part, through mesothelial cell/lysophosphatidic acid
      induced inflammatory response in ovarian cancer cells. The aim of this study was
      to elucidate the molecular mechanisms of the interactions between tumor cells and
      the cellular components of the ovarian cancer peritoneal microenvironment,
      specifically, mesothelial cells and macrophages. We found that SPARC not only
      significantly reduced macrophage chemoattractant protein-1 production and its
      macrophage chemotactic effect, but also attenuated the response of ovarian cancer
      cells to the mitogenic and proinvasive effects of macrophage chemo-attractant
      protein-1 and decreased macrophage-induced cancer cell invasiveness.
      Overexpression of SPARC in ovarian cancer cells significantly attenuated
      macrophage- and mesothelial cell-induced production and activity of interleukin
      6, prostanoids (prostaglandins E2 and 8-isoprostanes) as well as matrix
      metalloproteinases and urokinase plasminogen activator. Moreover, the effects of
      SPARC overexpression in ovarian cancer cells were mediated, in part, through
      inhibition of nuclear factor-kappaB promoter activation. These results indicate,
      for the first time, that the effects of tumor SPARC as a negative regulator of
      ovarian cancer are mediated through decreased recruitment of macrophages and
      downregulation of the associated inflammation.

PMID- 18813350
TI  - Distinct patterns of structural and numerical chromosomal instability
      characterize sporadic ovarian cancer.
AB  - Sporadic ovarian cancer is a particularly aggressive tumor characterized by
      highly abnormal karyotypes exhibiting many features of genomic instability. More
      complex genomic changes in tumors arise as a consequence of chromosomal
      instability (CIN), which can generate both numerical [(N)-CIN] and structural
      chromosomal instability [(S)-CIN]. In this study, molecular cytogenetic analysis
      was used to evaluate the relative levels of both (N)-CIN and (S)-CIN. Six tumors
      had a near-diploid chromosome number, two were near-tetraploid, and two were near
      triploid. (N)-CIN levels increased as a function of overall tumor genomic
      content, with near-diploid tumors exhibiting numerical instability indices
      ranging from 7.0 to 21.0 and near-tetraploid and triploid tumors exhibiting
      instability indices ranging from 24.9 to 54.9. In contrast, the extent of (S)-CIN
      was generally more evident in the diploid tumors compared with the near
      tetraploid tumors. To determine whether the associated chromosomal constitution
      and/or ploidy changes were influenced by mitotic segregation errors, centrosome
      analyses were performed on all 10 tumors. The near-diploid tumors, with the
      lowest numerical change, were observed to possess fewer cells with centrosome
      abnormalities (5.5% to 14.0%), whereas the near-tetraploid tumors possessed much
      higher levels of (N)-CIN and were characterized by a trend of elevating
      percentages of cells with abnormal centrosomes (16.0% to 20.5%). These
      observations suggest that two distinct processes governing genome stability may
      be disrupted in ovarian cancer: those that impact on numerical segregation and
      ploidy of chromosomes and those that affect the fidelity of DNA repair and lead
      to structural aberrations.

PMID- 18813351
TI  - p16 expression differentiates high-risk gastrointestinal stromal tumor and
      predicts poor outcome.
AB  - Gastrointestinal stromal tumors (GISTs) are characterized by alterations in genes
      involved in cell cycle regulation. Although p16 (INK4A) have been extensively
      investigated in GISTs, there are still discrepancies regarding its prognostic
      value. Therefore, we evaluated the clinical occurrence, diagnostic and prognostic
      value of p16 staining in GIST. One hundred one patients (54 women and 47 men)
      with a mean age of 64.1 years (range, 17-94 years) were surgically treated for a
      GIST within a 10-year period. Of these patients, 28 (28%) were affected by
      metastases (mean follow-up, 4.5 years). In 36 patients (36%), GIST occurred
      coincidentally with other malignancies. Expression of c-kit was confirmed in 97
      GIST patients (96%). In patients with high-risk GIST, the expression of p16
      expression was highly predictive for poor prognosis, i.e., the development of
      recurrence or metastases (P = .006) and poor survival (P = .004). In addition,
      the expression of p16 was highly predictive for reduction of the survival in
      patients who were affected by metastases or recurrence (P = .041). The disease
      specific and disease-free 1-, 3-, and 5-year survival rate was 96%, 90%, and 85%
      and 81%, 77%, and 72%, respectively. Primary tumor state, tumor size, and high
      risk classification were confirmed as relevant predictors for unfavorable
      prognosis in GIST (P < .001). Our results indicate that in high-risk GIST and in
      patients with recurrence or metastases, the expression of p16 is highly
      predictive for poor outcome. Thus, in addition to high-risk classification, p16
      expression might be an indicator for "very high risk GIST."

PMID- 18813352
TI  - Quantification of hTERT splice variants in melanoma by SYBR green real-time
      polymerase chain reaction indicates a negative regulatory role for the beta
      deletion variant.
AB  - Telomerase activity is primarily determined by transcriptional regulation of the
      catalytic subunit, human telomerase reverse transcriptase (hTERT). Several mRNA
      splice variants for hTERT have been identified, but it is not clear if telomerase
      activity is determined by the absolute or relative levels of full-length
      (functional) and variant hTERT transcripts. We have developed an SYBR green-based
      reverse transcription-quantitative polymerase chain reaction assay for the
      enumeration of the four common hTERT mRNA variants and correlated these with
      telomerase activity and telomere length in 24 human melanoma cell lines. All
      except five of the lines expressed four hTERT transcripts, with an overall
      significant level of co-occurrence between absolute mRNA levels of full-length
      alpha+/beta+ hTERT and the three splice variants alpha-/beta+, alpha+/beta-, and
      alpha-/beta-. On average, alpha+/beta+ made up the majority (48.1%) of
      transcripts, followed by alpha+/beta- (44.6%), alpha-/beta- (4.4%), and alpha
      /beta+ (2.9%). Telomerase activity ranged from 1 to 247 relative telomerase
      activity and correlated most strongly with the absolute amount of alpha+/beta+ (R
      = 0.791, P = .000004) and the relative amount of alpha+/beta- (R = -0.465, P =
      .022). This study shows that telomerase activity in melanoma cells is best
      determined by the absolute expression of full-length hTERT mRNA and indicates a
      role for the hTERT beta deletion variant in the negative regulation of enzyme
      activity.

PMID- 18813353
TI  - Clinical evaluation of M30 and M65 ELISA cell death assays as circulating
      biomarkers in a drug-sensitive tumor, testicular cancer.
AB  - Circulating full-length and caspase-cleaved cytokeratin 18 (CK18) are considered
      biomarkers of chemotherapy-induced cell death measured using a combination of the
      M30 and M65 ELISAs. M30 measures caspase-cleaved CK18 produced during apoptosis
      and M65 measures the levels of both caspase-cleaved and intact CK18, the latter
      of which is released from cells undergoing necrosis. Previous studies have
      highlighted their potential as prognostic, predictive, and pharmacological tools
      in the treatment of cancer. Disseminated testicular germ cell cancer (TC) is a
      paradigm for a chemosensitive solid malignancy of epithelial origin and has a
      cure rate of 80% to 90%. We conducted M30/M65 analyses on 34 patients with TC
      before and during treatment with bleomycin, etoposide, and cisplatin and showed
      that prechemotherapy serum levels of M65 and M30 antigens are correlated with
      established TC tumor markers lactate dehydrogenase, alpha-fetoprotein, and beta
      human chorionic gonadotropin, probably reflecting tumor load. Cumulative
      percentage change of M65 and M30 from baseline to end of study was highest in
      poor prognosis patients (P < .05). Moreover, area under the curve profiles of M65
      and M30 during chemotherapy mirrored dynamic profiles for lactate dehydrogenase,
      alpha-fetoprotein, and beta-human chorionic gonadotropin. Consequently, M65 and
      M30 levels appear to reflect chemotherapy-induced changes that correlate with
      changes in markers routinely used in the clinic for management of patients with
      TC. This is the first clinical study where M65 and M30 antigen levels correlate
      with established prognostic markers and provides impetus for their exploration in
      other epithelial cancers where there is a pressing need for informative
      circulating biomarkers.

PMID- 18813354
TI  - Progression of epididymal maldevelopment into hamartoma-like neoplasia in VHL
      disease.
AB  - Inactivation of the von Hippel-Lindau (VHL) gene and activation of the hypoxia
      inducible factor (HIF) in susceptible cells precedes formation of tumorlets and
      frank tumor in the epididymis of male VHL patients. We performed detailed
      histologic and molecular pathologic analysis of tumor-free epididymal tissues
      from VHL patients to obtain further insight into early epididymal tumorigenesis.
      Four epididymides from two VHL patients were serially sectioned to allow for
      three-dimensional visualization of morphologic changes. Areas of interest were
      genetically analyzed by tissue microdissection, immunohistochemistry for HIF and
      markers for mesonephric differentiation, and in situ hybridization for HIF
      downstream target vascular endothelial growth factor. Structural analysis of the
      epididymides revealed marked deviations from the regular anatomic structure
      resulting from impaired organogenesis. Selected efferent ductules were
      represented by disorganized mesonephric cells, and the maldeveloped mesonephric
      material was VHL-deficient by allelic deletion analysis. Furthermore, we observed
      maldeveloped mesonephric material near cystic structures, which were also VHL
      deficient and were apparent derivatives of maldeveloped material. Finally, a
      subset of VHL-deficient cells was structurally integrated in regular efferent
      ductules; proliferation of intraductular VHL-deficient cells manifests itself as
      papillary growth into the ductular lumen. Furthermore, we clarify that that there
      is a pathogenetic continuum between microscopic tumorlets and formation of tumor.
      In multiple locations, three-dimensional reconstruction revealed papillary growth
      to extend deeply into ductular lumina, indicative of progression into early
      hamartoma-like neoplasia. We conclude epididymal tumorigenesis in VHL disease to
      occur in two distinct sequential steps: maldevelopment of VHL-deficient
      mesonephric cells, followed by neoplastic papillary proliferation.

PMID- 18813355
TI  - The cytoplasmic domain of proEGF negatively regulates motility and elastinolytic
      activity in thyroid carcinoma cells.
AB  - The intracellular domains of the membrane-anchoring regions of some precursors of
      epidermal growth factor (EGF) family members have intrinsic biologic activities.
      We have determined the role of the human proEGF cytoplasmic domain (proEGFcyt) as
      part of the proEGF transmembrane-anchored region (proEGFctF) in the regulation of
      motility and elastinolytic invasion in human thyroid cancer cells. We found
      proEGFctF to act as a negative regulator of motility and elastin matrix
      penetration and the presence of proEGFcyt or proEGF22.23 resulted in a similar
      reduction in motility and elastinolytic migration. This activity was counteracted
      by EGF-induced activation of EGF receptor signaling. Decreased elastinolytic
      migratory activity in the presence of proEGFctF and proEGFcyt/proEGF22.23
      coincided with decreased secretion of elastinolytic procathepsin L. The presence
      of proEGFctF and proEGFcyt/proEGF22.23 coincided with the specific
      transcriptional up-regulation of t-SNARE member SNAP25. Treatment with siRNA
      SNAP25 resulted in motility and elastin migration being restored to normal
      levels. Epidermal growth factor treatment down-regulated SNAP25 protein by
      activating EGF receptor-mediated proteasomal degradation of SNAP25. These data
      provide first evidence for an important function of the cytoplasmic domain of the
      human proEGF transmembrane region as a novel suppressor of motility and cathepsin
      L-mediated elastinolytic invasion in human thyroid carcinoma cells and suggest
      important clinical implications for EGF-expressing tumors.

PMID- 18813356
TI  - Integrated nanosensors to determine levels and functional activity of human
      telomerase.
AB  - Telomerase is a key oncogenic enzyme, and a number of novel telomerase inhibitors
      are currently under development. Because inhibition can be achieved either at the
      protein or at the enzymatic activity level, independent measurements of these
      parameters are important in the development of effective therapeutic agents. In
      the current study, we have developed a set of functional magnetic nanosensors
      capable of measuring the concentration of telomerase, as well as its enzymatic
      activity in parallel. The method is based on a magnetic relaxation switch assay,
      which can be performed in crude tissue samples and is fast and extremely
      sensitive. Using this method, we were able to detect different amounts of
      telomerase protein and activity in various cancer and normal cell lines.
      Furthermore, we were able to study the effect of phosphorylation on telomerase
      activity. This system not only could provide a rapid assay for the evaluation of
      antitelomerase therapies but could also be implemented to the study of other
      cancer markers.

PMID- 18813357
TI  - Transformation by oncogenic Ras expands the early genomic response to
      transforming growth factor beta in intestinal epithelial cells.
AB  - A substantial body of evidence implicates TGFbeta as a tumor promoter in
      epithelial cells that have become resistant to its tumor suppressor activity. To
      better understand early, genome-wide TGFbeta responses in cells resistant to
      growth inhibition by TGFbeta, we used microarray analysis in a well-defined cell
      culture system of sensitive and resistant intestinal epithelial cells. TGFbeta
      regulated gene expression in TGFbeta-growth-sensitive, nontransformed rat
      intestinal epithelial cells (RIE-1) was compared to expression in TGFbeta-growth
      resistant RIE cells stably transformed by oncogenic Ras(12V). Treatment of RIE-1
      cells with 2 ng/ml TGFbeta1 for 1 hour increased the expression of eight gene
      sequences by 2.6-fold or more, whereas eight were down regulated 2.6-fold. In RIE
      Ras(12V) cells, 42 gene sequences were upregulated and only 3 were down
      regulated. Comparison of RIE and RIE-Ras(12V) identified 37 gene sequences as
      unique, Ras-dependent genomic targets of TGFbeta1. TGFbeta-regulation of
      connective tissue growth factor and vascular endothelial growth factor, two genes
      up-regulated in RIE-Ras cells and previously implicated in tumor promotion, was
      independently confirmed and further characterized by Northern analysis. Our data
      indicate that overexpression of oncogenic Ras in intestinal epithelial cells
      confers a significantly expanded repertoire of robust, early transcriptional
      responses to TGFbeta via signaling pathways yet to be fully elucidated but
      including the canonical Raf-1/MAPK/Erk pathway. Loss of sensitivity to growth
      inhibition by TGFbeta does not abrogate TGFbeta signaling and actually expands
      the early transcriptional response to TGFbeta1. Expression of some of these genes
      may confer to Ras-transformed cells characteristics favorable for tumor
      promotion.

PMID- 18813358
TI  - Plasminogen activator inhibitor 1 protects fibrosarcoma cells from etoposide
      induced apoptosis through activation of the PI3K/Akt cell survival pathway.
AB  - High levels of plasminogen activator inhibitor (PAI-1) in tumors are associated
      with poor prognosis in several cancer types, and the reason for this association
      is not fully understood. Plasminogen activator inhibitor 1 has been suggested to
      contribute to tumor growth by protecting cancer cells from apoptosis, and we have
      previously shown that wild type murine fibrosarcoma cells are significantly more
      resistant to apoptosis induced by chemotherapy than PAI-1-deficient fibrosarcoma
      cells. Here, we further investigated the molecular mechanisms underlying the
      antiapoptotic function of PAI-1 focusing on the phosphatidylinositol 3-phosphate
      kinase (PI3K)/Akt cell survival pathway. We demonstrate that the activation level
      of the Akt cell survival pathway is reduced in PAI-1-deficient cells. Inhibition
      of either PI3K or Akt by synthetic inhibitors sensitized the wild type but not
      the PAI-1-deficient cells to etoposide-induced cell death. More importantly,
      reintroduction of PAI-1 expression in PAI-1-deficient cells induced an increase
      in Akt activity and protection against etoposide-induced apoptosis. Concordantly,
      silencing of PAI-1 by RNA interference in wild type fibrosarcoma cells decreased
      the level of active Akt, and this was accompanied by a sensitization of the cells
      to etoposide-induced cell death. Altogether, our data suggest that PAI-1
      influences sensitivity to etoposide-induced apoptosis through the PI3K/Akt cell
      survival pathway by acting upstream of PI3K and Akt. This points to PAI-1 as a
      possible therapeutic target in cancer diseases where PAI-1 inhibits chemotherapy
      induced apoptosis.

PMID- 18813359
TI  - Squalene selectively protects mouse bone marrow progenitors against cisplatin and
      carboplatin-induced cytotoxicity in vivo without protecting tumor growth.
AB  - Squalene, an isoprenoid antioxidant is a potential cytoprotective agent against
      chemotherapy-induced toxicity. We have previously published that squalene
      protects light-density bone marrow cells against cis-diamminedichloroplatinum(
      II) (cisplatin)-induced toxicity without protecting tumor cells in vitro. Here,
      we developed an in vivo mouse model of cisplatin and cis-diammine (cyclobutane
      1,1-dicarboxylato) platinum(II) (carboplatin)-induced toxicity to further
      investigate squalene-mediated LD-BM cytoprotection including the molecular
      mechanism behind selective cytoprotection. We found that squalene significantly
      reduced the body weight loss of cisplatin and carboplatin-treated mice. Light
      density bone marrow cells from squalene-treated mice exhibited improved formation
      of hematopoietic colonies (colony-forming unit-granulocyte macrophage).
      Furthermore, squalene also protected mesenchymal stem cell colonies (colony
      forming unit-fibroblast) from cisplatin and carboplatin-induced toxicity.
      Squalene-induced protection was associated with decreased reactive oxygen species
      and increased levels of glutathione and glutathione peroxidase/glutathione-S
      transferase. Importantly, squalene did not protect neuroblastoma, small cell
      carcinoma, or medulloblastoma xenografts against cisplatin-induced toxicity.
      These results suggest that squalene is a potential candidate for future
      development as a cytoprotective agent against chemotherapeutic toxicity.

PMID- 18813360
TI  - Noninvasive monitoring of breast cancer during neoadjuvant chemotherapy using
      optical tomography with ultrasound localization.
AB  - The purposes of this study were 1) to investigate the feasibility of using
      optical tomography in the near-infrared (NIR) spectrum combined with ultrasound
      (US) localization (NIR/US) in monitoring tumor vascular changes and assessing
      tumor pathological response during chemotherapy and 2) to compare the accuracy of
      NIR/US with magnetic resonance imaging (MRI) in predicting residual cancer after
      neoadjuvant chemotherapy. Eleven female patients were studied during treatments
      with a combined imager consisting of a commercially available US system coupled
      to an NIR imager. Contrast-enhanced MRI was performed before treatment and
      surgery. Tumor vascular content was assessed based on total hemoglobin
      concentration and volume obtained from NIR data. A percentage blood volume index
      (%BVI) was calculated as the percentage ratio of the product of total hemoglobin
      concentration and volume normalized to pretreatment values. At treatment
      completion, pathologic assessment revealed three response groups: complete or
      near-complete responders (A), partial responders (B), and nonresponders (C). The
      mean %BVIs of groups A, B, and C at the treatment completion were 29.1 +/- 6.9%,
      46.3 +/- 3.7%, and 86.8 +/- 30.1%, respectively (differences statistically
      significant, P < .04). At the end of cycle 2, the %BVI of group A was noticeably
      lower than that of the partial (P = .091) and nonresponder groups (P = .075).
      Both NIR/US and MRI were equally effective in distinguishing different response
      groups in this pilot study. Our initial findings indicate that NIR/US using %BVI
      can be used during chemotherapy to repeatedly monitor tumor vascular changes.
      NIR/US also may evaluate pathologic response during treatment allowing for
      tailoring therapies to response.

PMID- 18813362
TI  - Design and its limitations in the construction of bi- and poly-nuclear
      coordination complexes and coordination polymers (aka MOFs): a personal view.
AB  - This article, presented from a personal point of view, is concerned with the
      design of ligands intended to give specifically either binuclear or tetranuclear
      metal complexes or coordination polymers. No attempt is made to provide a
      comprehensive coverage of these topics, the focus being mainly upon results from
      our laboratory. Some emphasis is placed upon aspects of the historical
      development of the deliberate construction of coordination polymers (aka MOFs)-
      materials promising useful applications, the study of which continues to expand
      exponentially. Some of our recent research is described in which the carbonate
      ion and the tetracyanoquinodimethane dianion are used as bridging ligands to
      generate targeted coordination polymers. It is intended that Dalton Perspectives
      be easily comprehensible to non-specialists in the field; an average second year
      university chemistry student should be easily able to understand the present
      contribution.

PMID- 18813361
TI  - Telomeric trans-silencing in Drosophila melanogaster: tissue specificity,
      development and functional interactions between non-homologous telomeres.
AB  - BACKGROUND: The study of P element repression in Drosophila melanogaster led to
      the discovery of the telomeric Trans-Silencing Effect (TSE), a homology-dependent
      repression mechanism by which a P-transgene inserted in subtelomeric
      heterochromatin (Telomeric Associated Sequences, "TAS") has the capacity to
      repress in trans, in the female germline, a homologous P-lacZ transgene located
      in euchromatin. TSE can show variegation in ovaries, displays a maternal effect
      as well as an epigenetic transmission through meiosis and involves
      heterochromatin and RNA silencing pathways. PRINCIPAL FINDINGS: Here, we analyze
      phenotypic and genetic properties of TSE. We report that TSE does not occur in
      the soma at the adult stage, but appears restricted to the female germline. It is
      detectable during development at the third instar larvae where it presents the
      same tissue specificity and maternal effect as in adults. Transgenes located in
      TAS at the telomeres of the main chromosomes can be silencers which in each case
      show the maternal effect. Silencers located at non-homologous telomeres
      functionally interact since they stimulate each other via the maternally
      transmitted component. All germinally-expressed euchromatic transgenes tested,
      located on all major chromosomes, were found to be repressed by a telomeric
      silencer: thus we detected no TSE escaper. The presence of the euchromatic target
      transgene is not necessary to establish the maternal inheritance of TSE,
      responsible for its epigenetic behavior. A single telomeric silencer locus can
      simultaneously repress two P-lacZ targets located on different chromosomal arms.
      CONCLUSIONS AND SIGNIFICANCE: Therefore TSE appears to be a widespread phenomenon
      which can involve different telomeres and work across the genome. It can explain
      the P cytotype establishment by telomeric P elements in natural Drosophila
      populations.

PMID- 18813364
TI  - Synthesis, structure and magnetic properties of linear heterobimetallic
      trinuclear Mn2Ln (Ln = Eu, Gd, Dy) complexes.
AB  - The reaction of (S)P[N(CH(3))N=CH-C(6)H(3)-2-OH-3-OCH(3)](3) with a Mn(II) salt
      followed by a Ln(III) salt (Ln = Eu, Gd and Dy), afforded linear heterometallic
      complexes [L(2)Mn(2)Ln](+) that showed interesting magnetic properties.

PMID- 18813365
TI  - [Bi5(dpd)6 within CH3CN](ClO4)3.3CH3CN: a supramolecular, tetrahedral
      pentabismuth cluster derived from a nonabismuth oxo/hydroxide.
AB  - The novel tetrahedral [Bi(5)(dpd)(6) within CH(3)CN](ClO(4))(3).3CH(3)CN (dpd =
      di-2-pyridyl-gem-diolate) has been synthesized from [Bi(9)(mu(3)-O)(8)(mu(3)
      OH)(6)](ClO(4))(5) and di-2-pyridyl ketone. The Bi(5) complex incorporates
      CH(3)CN via C-HO hydrogen bonding.

PMID- 18813363
TI  - Fe(II)/alpha-ketoglutarate hydroxylases involved in nucleobase, nucleoside,
      nucleotide, and chromatin metabolism.
AB  - Fe(II)/alpha-ketoglutarate-dependent hydroxylases uniformly possess a double
      stranded beta-helix fold with two conserved histidines and one carboxylate
      coordinating their mononuclear ferrous ions. Oxidative decomposition of the alpha
      keto acid is proposed to generate a ferryl-oxo intermediate capable of
      hydroxylating unactivated carbon atoms in a myriad of substrates. This
      Perspective focuses on a subgroup of these enzymes that are involved in
      pyrimidine salvage, purine decomposition, nucleoside and nucleotide
      hydroxylation, DNA/RNA repair, and chromatin modification. The varied reaction
      schemes are presented, and selected structural and kinetic information is
      summarized.

PMID- 18813366
TI  - A structural, spectroscopic and computational study of the molecular and
      electronic structure of a [bis(alpha-diiminato)manganese(II)] pi radical complex.
AB  - The synthesis, molecular and electronic structure of the first bis(alpha
      diiminato)manganese(II) complex are reported, [Mn(II)(L )(2)] (S(t) = (3)/(2))
      where (L )(1-) represents the one-electron reduced form of N,N'-bis(2,6
      isopropylphenyl)-1,4-diaza-1,3-diene; density functional theoretical calculations
      using the B3LYP functional and the broken symmetry approach BS(5,2) corroborate
      the presence of a high-spin Mn(II) ion and two ligand pi radical monoanions.

PMID- 18813367
TI  - Spin canting in an unprecedented three-dimensional pyrophosphate- and 2,2'
      bipyrimidine-bridged cobalt(II) framework.
AB  - The three-dimensional cobalt(ii) compound of formula
      {[Co(2)(P(2)O(7))(bpym)(2)].12H(2)O}(n), where the pyrophosphate and 2,2'
      bipyrimidine act as bridging ligands, is a new example of a spin-canted
      antiferromagnet with T(c) = 19 K.

PMID- 18813368
TI  - Facile synthesis of urchin-like glass/nickel core/shell composite hollow spheres.
AB  - Novel urchin-like core/shell composite hollow spheres were fabricated by assembly
      of nickel nanocones on the surface of hollow glass spheres; the effects of some
      reaction parameters on the morphology of the shell layers and the room
      temperature magnetic properties of the products were investigated.

PMID- 18813369
TI  - Structural motifs of diiodine complexes with amides and thioamides.
AB  - The reaction of 2-pyrimidone hydrochloride ([C(4)H(5)N(2)O](+)[Cl](-) or
      [PMOH(2)](+)[Cl](-)) with diiodine in a dichloromethane-methanol solution
      resulted in the formation of ([C(4)H(5)N(2)O](+))(2)[I(2)Cl(2)](2-) (1) complex.
      The compound was characterized by elemental analysis, FT-IR, DTA-TG and
      conductivity titrations. The crystal structure of 1 was also determined by X-ray
      diffraction at 294(1) K. Compound 1 is monoclinic, space group P2(1)/n,
      consisting of two cationic [PMOH(2)](+) species and a [I(2)Cl(2)](2-) counter
      dianion. The cation is in its keto form. Direct reaction of thiazolidine-2-thione
      (tzdtH), with diiodine in dichloromethane solution, on the other hand, led to the
      formation of a crystalline solid which contained two complexes of formulae
      [(tzdtH)(2)I](+)[I(3)](-).2I(2) (2) and [(tzdtH)I(2)](2).I(2) (2a) in a ratio of
      90 to 10%. Complex 2a was characterized by X-ray analysis at 180(2) K. Compound
      is monoclinic, space group C2/c and contains two units of [(tzdtH)I(2)] "spoke"
      structures. Compound 1, as well as the known species iodonium salt
      [(tzdtH)(2)I](+)[I(3)](-).2I(2) (2) and the charge transfer (CT) iodine complexes
      of formulae [(bztzdtH)I(2)] (3) and [(bztzdtH)I(2)].I(2) (4) (bztzdtH = 2
      mercaptobenzothiazole) with "spoke" and extended "spoke" structures respectively,
      were tested for their oxidizing activity towards 3,5-di-tert-butylcatechol to 3,5
      di-tert-butyl-o-benzoquinone.

PMID- 18813370
TI  - Influence of polyoxometalate ligands on the nature of high-valent transition
      metal nitrido species. A theoretical analysis of experimentally known and
      unprecedented compounds.
AB  - The electronic structure of group 6-8 transition metal (TM) nitrido derivatives
      [PW(11)O(39){TM(VI)N}](4-) is studied computationally and the potential
      reactivity of the polyoxoanions is discussed. The observed electrophilic
      reactivity for the Ru(VI) nitrido derivative is rationalized from frontier
      molecular orbital analysis. When we move to the left or down in the periodic
      table (TM = Os, Tc, Re, Mo and W) the electrophilic character of the
      polyoxometalate decreases or the cluster should be better regarded as a
      nucleophile. The DFT analysis of the redox properties suggests that the still
      unknown high-valent Mn(VI)N and Fe(VI)N units could be stabilized by the
      porphyrin-like ligand [PW(11)O(39)](7-) and their electronic structure indicates
      that these anions should have a high potential reactivity towards nucleophiles.

PMID- 18813371
TI  - Dynamic crystal-to-crystal conversion of a 3D-3D coordination polymer by de- and
      re-hydration.
AB  - A reversible crystal-to-crystal transformation of a 3D lead(II) coordination
      polymer with the ligand 4-pyridinecarboxylic acid (4-Hpyc), from [Pb(4
      pyc)(2)(H(2)O)](n) (1) to [Pb(4-pyc)(2)](n) (2) by de- and re-hydration, has been
      observed and the structures of 1 and 2 were 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 phase transitions observed for the single crystals
      also occur in the batch powder samples and lead to mono phasic products.

PMID- 18813372
TI  - Facile cyanamide-ammonia coupling mediated by cis- and trans-[PtIIL2] centers and
      giving metal-bound guanidines.
AB  - Diffusion of ammonia into CH(2)Cl(2) solutions of the dialkylcyanamide complexes
      cis- or trans-[PtCl(2)(RCN)(2)] (R = NMe(2), NEt(2), NC(5)H(10)) at 20-25 degrees
      C leads to metal-mediated cyanamide-ammonia coupling to furnish, depending on
      reaction time, one or another type of novel bisguanidine compound, i.e. the
      molecular cis- or trans-[PtCl(2){NH=C(NH(2))R}(2)] (cis- and trans-) and the
      cationic cis- or trans-[Pt(NH(3))(2){NH=C(NH(2))R}(2)](Cl)(2) (cis- and trans-)
      complexes. Compounds cis- or trans- were converted to cis- or trans-,
      accordingly, upon prolonged treatment with NH(3) in CH(2)Cl(2). The ammination of
      the relevant nitrile complexes cis- or trans-[PtCl(2)(RCN)(2)] (R = Et, CH(2)Ph,
      Ph) in CH(2)Cl(2) solutions affords only the cationic compounds cis- or trans
      [Pt(NH(3))(2){NH=C(NH(2))R}(2)](Cl)(2) (cis- and trans-). The formulation of was
      supported by satisfactory C, H and N elemental analyses, agreeable ESI(+)-MS (or
      FAB(+)-MS), IR, (1)H and (13)C NMR spectroscopies. The structures of trans-,
      trans-, cis-, trans-, cis-, and cis- were determined by single-crystal X-ray
      diffraction disclosing structural features and showing that the ammination gives
      ligated guanidines and amidines in the E- and Z-forms, respectively, where both
      correspond to the trans-addition of NH(3) to the nitrile species.

PMID- 18813373
TI  - Assembly of tetra, di and mononuclear molecular cadmium phosphonates using 2,4,6
      triisopropylphenylphosponic acid and ancillary ligands.
AB  - The reaction of ArPO(3)H(2) (Ar = 2,4,6-iPr(3)-C(6)H(2)) with
      Cd(CH(3)COO)(2).2H(2)O using various co-ligands such as methanol,
      dimethylformamide (DMF) and 3,5-dimethylpyrazole (DMPZH) resulted in the
      formation of tetranuclear assemblies
      [Cd(4)(ArPO(3))(2)(ArPO(3)H)(4)(CH(3)OH)(4)].3(CH(3)OH) (1),
      [Cd(4)(ArPO(3))(2)(ArPO(3)H)(4)(DMF)(4)].3(DMF) (2) and
      [Cd(4)(ArPO(3))(2)(ArPO(3)H)(4)(DMF)(2)(DMPZH)(2)].2(DMF).2(H(2)O) (3). In all of
      these compounds the tetranuclear cadmium array, containing two five-coordinate
      and two six-coordinate cadmium atoms, is held together by two mu(4) capping
      [ArPO(3)](2-) and four anisobidentate mu(2) [ArPO(2)(OH)](-) ligands. Each
      cadmium atom is bound to an additional ancillary ligand. The reaction of
      ArPO(3)H(2) with Cd(CH(3)COO)(2).2H(2)O in the presence of the chelating ligand
      2,2'-bipyridine (bipy) leads to the exclusive formation of the dinuclear assembly
      [Cd(2)(ArPO(3)H)(4)(bipy)(2)].(CH(3)OH)(H(2)O) (4). The latter contains an eight
      membered Cd(2)P(2)O(4) inorganic ring formed as a result of the bridging
      coordination action of two anisobidentate mu(2) [ArPO(2)(OH)](-) ligands. Each
      cadmium atom is bound by one chelating bipy and one monodentate [ArPO(2)(OH)](-)
      ligands. Use of four equivalents of 3,5-dimethylpyrazole leads to the formation
      of the mononuclear derivative [Cd(ArPO(3)H)(2)(DMPZH)(4)] (5). The molecular
      structure of the latter comprises of a central cadmium atom surrounded by six
      monodentate ligands. Four of these are neutral pyrazole ligands that occupy the
      equatorial plane; the remaining two are anionic phosphinate ligands which are
      present trans to each other. The thermal analysis of 1 and 4 reveals that the
      char residue obtained at 600 degrees C consists predominantly of Cd(2)P(2)O(7).

PMID- 18813374
TI  - Iridium derivatives of fluorinated aromatics by C-H activation: isolation of
      classical and non-classical hydrides.
AB  - A reaction of trans-[Ir(H)(5)(PiPr(3))(2)] (1) with 2,3,5,6-tetrafluoropyridine,
      pentafluorobenzene or 1,3-difluorobenzene in the presence of neohexene affords
      the square-pyramidal C-H activation products cis-trans-[Ir(4
      C(5)NF(4))(H)(2)(PiPr(3))(2)] (2), cis-trans-[Ir(C(6)F(5))(H)(2)(PiPr(3))(2)] (4)
      and cis-trans-[Ir(2-C(6)H(3)F(2))(H)(2)(PiPr(3))(2)] (6). Irradiation of complex
      1 with 2,3,5,6-tetrafluoropyridine or pentafluorobenzene gave the hydrides cis
      trans-[Ir(4-C(5)NF(4))(H)(2)(H(2))(PiPr(3))(2)] (3) or cis-trans
      [Ir(C(6)F(5))(H)(2)(H(2))(PiPr(3))(2)] (5). The presence of non-classical bound
      H(2) moieties has been demonstrated by the measurement of T(1) times at different
      temperatures. For 3 the H-H distance in the H(2) ligand can be estimated to be
      0.82 A. The dihydride compounds 2, 4 and 6 react with CO to yield the complexes
      cis-trans-[Ir(Ar)(H)(2)(CO)(PiPr(3))(2)] (7: Ar = 4-C(5)NF(4), 8: Ar = C(6)F(5),
      9: Ar = 2-C(6)H(3)F(2)). A reaction of 2 or 3 with an excess of ethylene leads to
      the formation of ethane and the Ir(i) ethylene complex trans-[Ir(4
      C(5)NF(4))(eta(2)-C(2)H(4))(PiPr(3))(2)] (10). Treatment of 10 with CO furnishes
      the Ir(i) complex trans-[Ir(4-C(5)NF(4))(CO)(PiPr(3))(2)] (11).

PMID- 18813375
TI  - CuII binding sites located at His-96 and His-111 of the human prion protein:
      thermodynamic and spectroscopic studies on model peptides.
AB  - The prion protein (PrP) is a Cu(2+)-binding cell-surface glycoprotein. Using PrP
      peptide fragments, by means of potentiometric, spectroscopic and thermodynamic
      techniques, we have shown that Cu(2+) ions bind to the region comprising His-96,
      His-111 and the octarepeat domain within residues 60-91. Cu(2+) may bind in
      different modes, which strongly depend both on His position within the peptide
      sequence and on the adjacent residues. We have used a series of protected
      oligopeptides having His at the C- or the N-terminus, inducing different binding
      modes to amide nitrogens around the His residue, either towards the N- or C
      terminus. His imidazole acts as an anchoring site for Cu(2+) and then binding to
      ionized amide nitrogens follows. When it is directed towards the C-terminus the
      formation of a less stable seven-membered chelate ring with a {N(im), N(-)}
      binding mode occurs. When coordination goes towards the N-terminus the
      thermodynamically more stable six-membered chelate ring is formed. NMR data
      suggest that both the coordination modes are possible for the model peptides;
      however, the thermodynamic measurements show that they only slightly differ in
      energy and the influence of the adjacent amino acid residues can address the
      coordination toward the C- or the N-terminus.

PMID- 18813376
TI  - Copper-mediated imine-nitrile coupling leading to unsymmetric 1,3,5
      triazapentadienato complexes containing the incorporated iminoisoindolin-1-one
      moiety.
AB  - The copper(II)-mediated integration between various 3-iminoisoindolin-1-ones and
      neat organonitriles (which play a dual role of solvent and reactant), under
      heating for ca. 12 h, and without requiring any base, accomplishes the release of
      the solid (1,3,5-triazapentadienato)Cu(II) complexes
      [Cu{HN=C(R)N=C(C(6)R(1)R(2)R(3)R(4)CO)N}(2)] (1-11) bearing the incorporated
      iminoisoindolin-1-one fragment. These compounds were isolated in moderate to good
      yields (44-78%) and do not require further purification. The iminoisoindolinone
      nitrile coupling is Cu(II)-mediated and has a general character insofar as it can
      be efficiently applied for both unsubstituted (R(1)-R(4) = H) and substituted
      iminoisoindolin-1-ones (R(1), R(3), R(4) = H, R(2) = Me; R(1), R(4) = H, R(2),
      R(3) = Cl; R(1)-R(4) = F), and a wide range of nitriles (R = Me, Et, Pr(n),
      Pr(i), C(6)H(11), CH(2)Ph). Complexes 1-11 were characterized by elemental
      analyses (C, H, N), FAB(+)-MS, IR spectroscopy, and additionally compounds 1, 2
      and 4 by single-crystal X-ray diffraction.

PMID- 18813377
TI  - Platination of full length tRNA(Ala) and truncated versions of the acceptor stem
      and anticodon loop.
AB  - Nuclear DNA is a well characterized target for many low molecular metal-based
      drugs, with cisplatin and related antineoplastic compounds as typical examples.
      Much less is known concerning to what extent targeting of RNA may influence the
      activity spectrum of these types of drugs. In a preliminary communication by us
      (Papsai et al., Dalton Trans., 2006, 3515) we were able to show that the folded,
      three-dimensionally well defined structure of tRNA(Ala) readily interacts with
      cisplatin. In the present study we have further analyzed the binding preferences
      within the preferentially targeted stem region (sMh(Ala)) by modulation of the
      sequence around the G-U wobble base-pair and the net charge of the 3' and 5'
      ends. Our data show that the adduct profile is strongly influenced by the
      presence of the 5' end phosphate group. Further, the adduct formation reaction
      can be prevented by replacement of the G-U wobble base-pair with the fully
      complementary G-C pair. To further investigate the influence from local sequence
      on the platination process, a model of the anticodon region (acMh(Ala)) was also
      investigated. In the absence of consecutive guanine-residues in the stem- and
      anticodon regions, preferential platination was found to take place at the
      terminal AG-site in the stem region. However, after introduction of a GG-pair in
      the anticodon loop, platination was observed also here. At 37 degrees C, pH 6.3
      and C(Pt) = 0.10 mM the rate of platination was determined to be ca. 1 x 10(-4)
      s(-1), with the most rapid reaction observed for interaction with the anticodon
      model carrying two adjacent guanines in the single-stranded loop. Together, these
      data show that platination of RNA is highly sequence- and structure-dependent.

PMID- 18813378
TI  - Syntheses, structures and reactions of a series of beta-diketiminatoyttrium
      compounds.
AB  - This paper describes the synthesis and selected reactions of a series of
      crystalline mono(beta-diiminato)yttrium chlorides 3a, 3b, 4a, 4b, 5a, 5b, 5c and
      9. The X-ray structure of each has been determined, as well as of [YCl(L4)(2)]
      (6), [Y(L1)(2)OBu(t)] (7) and [Y{CH(SiMe(3))(2)}(thf)(mu-Cl)(2)Li(OEt(2))(2)(mu
      Cl)](2) (8). The N,N'-kappa(2)-beta-diiminato ligands were [{N(R)C(Me)}(2)CH](-)
      [R = C(6)H(4)Pr(i)-2 (L1); R = C(6)H(4)Bu(t)-2 (L2); R = C(6)H(3)Pr(i)(2)-2,6
      (L3)], [{N(SiMe(3))C(Ph)}(2)CH)](-) (L4) and [{N(C(6)H(3)Pr(i)(2)
      2,6)C(H)}(2)CPh](-) (L5). Equivalent portions of Li[L(x)] and YCl(3) in Et(2)O
      under mild conditions yielded [Y(mu-Cl)(L(x))(mu-Cl)(2)Li(OEt(2))(2)](2) [L(x) =
      (L1(3a)) or (L1(3b))] and [Y(mu-Cl)(L3)(mu-Cl)Li(OEt(2))(2)(mu-Cl)](2) (4a) or
      its thf (instead of Et(2)O) equivalent 4b. Each of the Li(OEt(2))(2)Cl(2)
      moieties is bonded in a terminal (3) or bridging (4) mode with respect to the two
      Y atoms; the difference is attributed to the greater steric demand of L3 than L1
      or L2. Under slightly more forcing conditions, YCl(3) and Li(L2) (via 3b) gave
      the lithium-free complex [YCl(2)(L2)(thf)(2)] (5b). Two isoleptic compounds 5a
      and 5c (having in place of L2 in 5b, L3 and L5, respectively) were obtained from
      YCl(3) and an equivalent portion of K[L3] and Na[L5], respectively; under the
      same conditions using Na[L4], the unexpected product was [YCl(L4)(2)] (6) (i.e.
      incorporating only one half of the YCl(3)). A further unusual outcome was in the
      formation of 8 from 3a and 2 Li[CH(SiMe(3))(2)]. Compound
      [Y(L5){N(H)C(6)H(3)Pr(i)(2)-2,6}(thf)(mu(3)-Cl)(2)K](2).4Et(2)O (9), obtained
      from and K[N(H)C(6)H(3)Pr(i)(2)-2,6], is noteworthy among group 3 or lanthanide
      metal (M) compounds for containing MClKCl (M = Y) moieties.

PMID- 18813380
TI  - MEMS and the microbe.
AB  - In recent years, relatively simple MEMS fabrications have helped accelerate our
      knowledge of the microbial cell. Current progress and challenges in the
      application of lab-on-a-chip devices to the viable microbe are reviewed.
      Furthermore, the degree to which microbiologists are becoming the engineers and
      are tailoring microbial cells and protocells as potential components for bioMEMS
      devices is highlighted. We conclude this is a highly productive time for
      microbiologists and microengineers to unite their shared interest in the micron
      scale world.

PMID- 18813381
TI  - Formation of artificial lipid bilayers using droplet dielectrophoresis.
AB  - We describe the formation of artificial bilayer lipid membranes (BLMs) by the
      controlled, electrical manipulation of aqueous droplets immersed in a lipid
      alkane solution. Droplet movement was generated using dielectrophoresis on planar
      microelectrodes covered in a thin insulator. Droplets, surrounded by lipid
      monolayers, were brought into contact and spontaneously formed a BLM. The method
      produced BLMs suitable for single-channel recording of membrane protein activity
      and the technique can be extended to create programmable BLM arrays and networks.

PMID- 18813382
TI  - Self-loading lithographically structured microcontainers: 3D patterned, mobile
      microwells.
AB  - We demonstrate mass-producible, mobile, self-loading microcontainers that can be
      used to encapsulate both non-living and living objects, thus forming three
      dimensionally patterned, mobile microwells.

PMID- 18813383
TI  - Electrokinetically driven fluidic transport in integrated three-dimensional
      microfluidic devices incorporating gold-coated nanocapillary array membranes.
AB  - Electrokinetically driven fluid transport was evaluated within three-dimensional
      hybrid nanofluidic-microfluidic devices incorporating Au-coated nanocapillary
      array membranes (NCAMs). Gold NCAMs, prepared by electroless gold deposition on
      polymeric track-etched membranes, were susceptible to gas bubble formation if the
      interfacial potential difference exceeded approximately 2 V along the length of
      the gold region. Gold membranes were etched to yield 250 microm wide coated
      regions that overlap the intersection of two orthogonal microfluidic channels in
      order to minimize gas evolution. The kinetics of electrolysis of water at the
      opposing ends of the gold region was modeled and found to be in satisfactory
      agreement with experimental measurements of the onset of gas bubble formation.
      Conditions to achieve electrokinetic injection across Au-coated NCAMs were
      identified, with significant reproducible injections being possible for NCAMs
      modified with this relatively thin gold stripe. Continuous gold films led to
      suppressed injections and to a variety of ion enrichment/depletion effects in the
      microfluidic source channel. The suppression of injections was understood through
      finite element modeling which revealed the presence of a significant
      electrophoretic velocity component in opposition to electroosmotic flow at the
      edge of the Au-dielectric regions.

PMID- 18813384
TI  - Biocompatible surfactants for water-in-fluorocarbon emulsions.
AB  - Drops of water-in-fluorocarbon emulsions have great potential for
      compartmentalizing both in vitro and in vivo biological systems; however,
      surfactants to stabilize such emulsions are scarce. Here we present a novel class
      of fluorosurfactants that we synthesize by coupling oligomeric perfluorinated
      polyethers (PFPE) with polyethyleneglycol (PEG). We demonstrate that these block
      copolymer surfactants stabilize water-in-fluorocarbon oil emulsions during all
      necessary steps of a drop-based experiment including drop formation, incubation,
      and reinjection into a second microfluidic device. Furthermore, we show that
      aqueous drops stabilized with these surfactants can be used for in vitro
      translation (IVT), as well as encapsulation and incubation of single cells. The
      compatability of this emulsion system with both biological systems and
      polydimethylsiloxane (PDMS) microfluidic devices makes these surfactants ideal
      for a broad range of high-throughput, drop-based applications.

PMID- 18813385
TI  - Microfluidic-based synthesis of non-spherical magnetic hydrogel microparticles.
AB  - Spherical and non-spherical magnetic hydrogel particles were synthesized in a
      microfluidic device containing an embedded UV light reflector. Monodisperse
      magnetic emulsion droplets were generated in a T-junction and allowed to relax
      into spheres, disks, and plugs in confining microchannel geometries. Particle
      morphology was locked-in via UV-initiated photopolymerization. The role of the
      reflector in the microchannel is to provide a uniform distribution of UV energy
      to the magnetic emulsion droplets and to increase the UV flux, which
      significantly improves UV polymerization conditions for microfluidic-based
      particle synthesis. Magnetic nanoparticles were uniformly encapsulated in the
      hydrogel, giving the microparticles superparamagnetic behavior. Additionally, the
      non-spherical particles show anisotropic responses under an applied external
      magnetic field.

PMID- 18813386
TI  - An integrated QCM-based narcotics sensing microsystem.
AB  - We present the design, fabrication and successful testing of a 14x14x4 mm3
      integrated electronic narcotics sensing system which consists of only four parts.
      The microsystem absorbs airborne narcotics molecules and performs a liquid assay
      using an integrated quartz crystal microbalance (QCM). A vertically conductive
      double-sided adhesive foil (VCAF) was used and studied as a novel material for
      LOC and MEMS applications and provides easy assembly, electrical contacting and
      liquid containment. The system was tested for measuring cocaine and ecstasy, with
      successful detection of amounts as small as 100 ng and 200 ng, respectively.
      These levels are of interest in security activities in customs, prisons and by
      the police.

PMID- 18813387
TI  - A microfluidic flow injection system for DNA assay with fluids driven by an on
      chip integrated pump based on capillary and evaporation effects.
AB  - A miniaturized flow injection analysis (FIA) system integrating a micropump on a
      microfluidic chip based on capillary and evaporation effects was developed. The
      pump was made by fixing a filter paper plug with a vent tube at the channel end,
      it requires no peripheral equipment and provides steady flow in the microl min(
      1) range for FIA operation. Valve-free sample injection was achieved at nanolitre
      level using an array of slotted vials. The practical applicability of the system
      was demonstrated by DNA assay with laser-induced fluorescence (LIF) detection. A
      precision of 1.6% RSD (10.0 ng microl(-1), n=15) was achieved with a sampling
      throughput of 76 h(-1) and sample consumption of 95 nl.

PMID- 18813388
TI  - A soft-polymer piezoelectric bimorph cantilever-actuated peristaltic micropump.
AB  - A peristaltic micropump was fabricated and characterized. The micropump was
      fabricated using soft lithography, and actuated using piezoelectric bimorph
      cantilevers. The micropump channel was formed by bonding two layers of PDMS,
      mixed at 5:1 and 30:1 ratios. The channel was fabricated in the 5:1 layer using
      replica molding (REM), where a very simple and inexpensive template was made by
      straddling a 75 microm wire over a glass substrate, followed by covering and
      smoothing over the wire with a piece of aluminium foil. Not only was this
      template inexpensive and extremely simple to fabricate, it also created a rounded
      cross-sectional geometry which is favorable for complete valve shutoff. The
      cantilevers were driven at Vp=+/-90 V with amplified square wave signals
      generated by a virtual function generator created in LabVIEW. Connections to the
      micropump were made by placing capillary tubes in the channel, and then sealed
      between the two layers of PDMS. Machined aluminium clamps were adhered to the
      tips of the cantilevers with general purpose adhesive. These clamps allowed for
      aluminium valves, with finely machined tips of dimensions 3 mm by 200 microm, to
      be held firmly in place. The variables characterized for this micropump were flow
      rate, maximum attainable backpressure, free cantilever deflection, valve shutoff,
      and valve leakage. Three actuation patterns with phase differences of 60, 90, and
      120 degrees were compared for flow rate and maximum backpressure. It was
      determined that the 120 degrees signal outperformed the 60 degrees and 90 degrees
      signals for both maximum flowrate and maximum attainable backpressure. The
      maximum and minimum flowrates demonstrated by the micropump were 289 nL min(-1)
      and 53 nL min(-1), respectively. The maximum backpressure attained was 35 300 Pa.
      It was also demonstrated that the valves fully closed the channels upon
      actuation, with minimal observed leakage.

PMID- 18813389
TI  - Electric field control and analyte transport in Si/SiO2 fluidic nanochannels.
AB  - This article presents an analysis of the electric field distribution and current
      transport in fluidic nanochannels fabricated by etching of a silicon chip. The
      channels were overcoated by a SiO2 layer. The analysis accounts for the current
      leaks across the SiO2 layer into the channel walls. Suitable voltage biasing of
      the Si substrate allows eliminating of the leaks or using them to modify the
      potential distribution of the fluid. Shaping the potential in the fluid can be
      utilized for solute focusing and separations in fluidic nanochannels.

PMID- 18813390
TI  - Laser-induced cavitation based micropump.
AB  - Lab-on-a-chip devices are in strong demand as versatile and robust pumping
      techniques. Here, we present a cavitation based technique, which is able to pump
      a volume of 4000 microm3 within 75 micros against an estimated pressure head of 3
      bar. The single cavitation event is created by focusing a laser pulse in a
      conventional PDMS microfluidic chip close to the channel opening. High-speed
      photography at 1 million frames s(-1) resolves the flow in the supply channel,
      pump channel, and close to the cavity. The elasticity of the material affects the
      overall fluid flow. Continuous pumping at repetition rates of up to 5 Hz through
      6 mm long square channels of 20 microm width is shown. A parameter study reveals
      the key-parameters for operation: the distance between the laser focus and the
      channel, the maximum bubble size, and the chamber geometry.

PMID- 18813391
TI  - Influence of micromixer characteristics on polydispersity index of block
      copolymers synthesized in continuous flow microreactors.
AB  - The influence of interdigital multilamination micromixer characteristics on
      monomer conversions, molecular weights and especially on the polydispersity index
      of block copolymers synthesized continuously in two microtube reactors is
      investigated. The micromixers are used to mix, before copolymerization, a polymer
      solution with different viscosities and the second monomer. Different geometries
      of micromixer (number of microchannels, characteristic lengths) have been
      studied. It was found that polydispersity indices of the copolymers follow a
      linear relationship with the Reynolds number in the micromixer, represented by a
      form factor. Thus, beside the operating conditions (nature of the first block and
      comonomer flow rate), the choice of the micromixer geometry and dimension is
      essential to control the copolymerization in terms of molecular weights and
      polydispersity indices. This linear correlation allows the prediction of
      copolymer features. It can also be a new method to optimize existing micromixers
      or design other geometries so that mixing could be more efficient.

PMID- 18813392
TI  - Perforated membrane method for fabricating three-dimensional polydimethylsiloxane
      microfluidic devices.
AB  - A procedure is described for making layer-to-layer interconnections in
      polydimethylsiloxane (PDMS) microfluidic devices. Thin (approximately 50 microm)
      perforated PDMS membranes are bonded to thicker (0.1 cm or more) PDMS slabs by
      means of thermally cured PDMS prepolymer to form a three-dimensional (3D) channel
      structure, which may contain channel or valve arrays that can pass over and under
      one another. Devices containing as many as two slabs and three perforated
      membranes are demonstrated. We also present 3D PDMS microfluidic devices for
      display and for liquid dispensing.

PMID- 18813393
TI  - Versatile control of multiphase laminar flow for in-channel microfabrication.
AB  - We have improved the multiphase laminar flow based in-channel fabrication method
      to overcome diffusion-induced broadening. A sheathing phase with protecting
      molecules confines metal wire deposition and allows for flexible control of the
      location, width, and uniformity of deposited metal wires. Two-layered T-junctions
      are introduced to form vertically stacked multiphase laminar flow. Combining
      these techniques, we fabricate quadrupole silver electrodes on the four sidewalls
      of rectangular polydimethylsiloxane (PDMS) microchannels that are 3 cm in length.

PMID- 18813395
TI  - A microarray to measure repair of damaged plasmids by cell lysates.
AB  - DNA repair mechanisms constitute major defences against agents that cause cancer,
      degenerative disease and aging. Different repair systems cooperate to maintain
      the integrity of genetic information. Investigations of DNA repair involvement in
      human pathology require an efficient tool that takes into account the variety and
      complexity of repair systems. We have developed a highly sensitive damaged
      plasmid microarray to quantify cell lysate excision/synthesis (ES) capacities
      using small amounts of proteins. This microsystem is based on efficient
      immobilization and conservation on hydrogel coated glass slides of plasmid DNA
      damaged with a panel of genotoxic agents. Fluorescent signals are generated from
      incorporation of labelled dNTPs by DNA excision-repair synthesis mechanisms at
      plasmid sites. Highly precise DNA repair phenotypes i.e. simultaneous
      quantitative measures of ES capacities toward seven lesions repaired by distinct
      repair pathways, are obtained. Applied to the characterization of xeroderma
      pigmentosum (XP) cells at basal level and in response to a low dose of UVB
      irradiation, the assay showed the multifunctional role of different XP proteins
      in cell protection against all types of damage. On the other hand, measurement of
      the ES of peripheral blood mononuclear cells from six donors revealed significant
      diversity between individuals. Our results illustrate the power of such a
      parallelized approach with high potential for several applications including the
      discovery of new cancer biomarkers and the screening of chemical agents
      modulating DNA repair systems.

PMID- 18813394
TI  - Microfluidic platform for real-time signaling analysis of multiple single T cells
      in parallel.
AB  - Deciphering the signaling pathways that govern stimulation of naive CD4+ T helper
      cells by antigen-presenting cells via formation of the immunological synapse is
      key to a fundamental understanding of the progression of successful adaptive
      immune response. The study of T cell-APC interactions in vitro is challenging,
      however, due to the difficulty of tracking individual, non-adherent cell pairs
      over time. Studying single cell dynamics over time reveals rare, but critical,
      signaling events that might be averaged out in bulk experiments, but these less
      common events are undoubtedly important for an integrated understanding of a
      cellular response to its microenvironment. We describe a novel application of
      microfluidic technology that overcomes many limitations of conventional cell
      culture and enables the study of hundreds of passively sequestered hematopoietic
      cells for extended periods of time. This microfluidic cell trap device consists
      of 440 18 micromx18 micromx10 microm PDMS, bucket-like structures opposing the
      direction of flow which serve as corrals for cells as they pass through the cell
      trap region. Cell viability analysis revealed that more than 70% of naive CD4+ T
      cells (TN), held in place using only hydrodynamic forces, subsequently remain
      viable for 24 hours. Cytosolic calcium transients were successfully induced in TN
      cells following introduction of chemical, antibody, or cellular forms of
      stimulation. Statistical analysis of TN cells from a single stimulation
      experiment reveals the power of this platform to distinguish different calcium
      response patterns, an ability that might be utilized to characterize T cell
      signaling states in a given population. Finally, we investigate in real time
      contact- and non-contact-based interactions between primary T cells and dendritic
      cells, two main participants in the formation of the immunological synapse.
      Utilizing the microfluidic traps in a daisy-chain configuration allowed us to
      observe calcium transients in TN cells exposed only to media conditioned by
      secretions of lipopolysaccharide-matured dendritic cells, an event which is
      easily missed in conventional cell culture where large media-to-cell ratios
      dilute cellular products. Further investigation into this intercellular signaling
      event indicated that LPS-matured dendritic cells, in the absence of antigenic
      stimulation, secrete chemical signals that induce calcium transients in T(N)
      cells. While the stimulating factor(s) produced by the mature dendritic cells
      remains to be identified, this report illustrates the utility of these
      microfluidic cell traps for analyzing arrays of individual suspension cells over
      time and probing both contact-based and intercellular signaling events between
      one or more cell populations.

PMID- 18813396
TI  - Microfluidic patterning of nanodisc lipid bilayers and multiplexed analysis of
      protein interaction.
AB  - We report a microfluidic method for precisely patterning lipid bilayers and a
      multiplexed assay to examine the interaction between the lipids and protein
      analytes. The lipids were packaged into nanoscale lipid bilayer particles known
      as Nanodiscs and delivered to surfaces using microfluidic channels. Two types of
      lipids were used in this study: biontinylated lipids and phosphoserine lipids.
      The deposition of biotinylated lipids on a glass surface was confirmed by
      attaching streptavidin coated quantum dots to the lipids, followed by fluorescent
      imaging. Using this multiplexed grid assay, we examined binding of annexin to
      phosphoserine lipids, and compared these results to similar analysis performed by
      surface plasmon resonance.

PMID- 18813397
TI  - Ionic current rectification at a nanofluidic/microfluidic interface with an
      asymmetric microfluidic system.
AB  - A nanofluidic-microfluidic interface is reported that rectifies ionic current
      using uncoated symmetric nanocapillaries. Previously, ionic current rectification
      has been achieved by other groups with nanochannels with differential coatings
      and in nanopores that are conical in shape. This simple device uses nanocapillary
      membranes (NCMs) with uncoated symmetric channels to connect a microfluidic
      channel and a larger solution reservoir. The conductivity of the solution in the
      microchannel appears to be critical in the formation of the low "off" state
      current and the high "on" state current. It is hypothesized that the "off" state
      current is low due to the formation of an ion depletion zone in the microchannel
      while the higher "on" state currents are produced by a zone of enhanced ionic
      concentration in the microchannel.

PMID- 18813398
TI  - An active bubble trap and debubbler for microfluidic systems.
AB  - We present a novel, fully integrated microfluidic bubble trap and debubbler. The
      2-layer structure, based on a PDMS valve design, utilizes a featured membrane to
      stop bubble progression through the device. A pneumatic chamber directly above
      the trap is evacuated, and the bubble is pulled out through the gas-permeable
      PDMS membrane. Normal device operation, including continuous flow at atmospheric
      pressure, is maintained during the entire trapping and debubbling process. We
      present a range of trap sizes, from 2 to 10 mm diameter, and can trap and remove
      bubbles up to 25 microL in under 3 h.

PMID- 18813399
TI  - Side-by-side comparison of disposable microchips with commercial capillary
      cartridges for application in capillary isoelectric focusing with whole column
      imaging detection.
AB  - Simple-structured, well-functioned disposable poly(dimethylsiloxane) (PDMS)
      microchips were developed for capillary isoelectric focusing with whole column
      imaging detection (CIEF-WCID). Side-by-side comparison of the developed
      microchips with well-established commercial capillary cartridges demonstrated
      that the disposable microchips have comparable performance as well as advantages
      such as absence of lens effect and possibility of high-aspect-ratio accompanied
      with a dramatic reduction in cost.

PMID- 18813400
TI  - Long-term storable and shippable lipid bilayer membrane platform.
AB  - The fragility and short lifetimes characteristic of conventionally formed lipid
      bilayer membranes has necessitated their preparation to be at the time and point
      of use. By using high freezing-point lipid-solvent mixtures, the process of lipid
      bilayer self-assembly may be reversibly arrested. In solid form, the bilayer
      precursor can be stored indefinitely and is sufficiently robust to withstand
      commercial shipping. Upon thawing, bilayer self-assembly resumes, resulting in a
      biologically functional membrane. Combination of this membrane precursor with an
      inexpensive chip results in a compact, practical, and disposable platform for ion
      channel measurements.

PMID- 18813401
TI  - Neutravidin micropatterning by deep UV irradiation.
AB  - We describe a novel approach for directly patterning neutravidin protein by
      exposure to deep UV irradiation. Neutravidin is physically absorbed onto the
      glass or quartz substrate, dehydrated in acetone and air-dried. Dry neutravidin
      coated samples are patterned either by top-side or back-side exposure to 185 nm
      UV. Subsequent introduction of fluorescent biotinylated proteins clearly
      demonstrates binding to the masked neutravidin regions and no binding to exposed
      areas. Patterned samples retain their protein affinity for at least three months
      of storage at room temperature.

PMID- 18813402
TI  - Wells score for venous thromboembolism. Basic diagnostic algorithm for venous
      thromboembolism.

PMID- 18813403
TI  - Glypican3 in genetically modified human monocyte-derived dendritic cells induced
      specific cytotoxity against glypican3 overexpressing human hepatocellular
      carcinoma cells in vitro.
AB  - OBJECTIVE: To transduce the new hepatocellular carcinoma (HCC) specific antigen
      gene glypican3 (GPC3) into dendritic cells (DCs) and to observe the in vitro
      cytotoxic effect induced by the genetically modified DCs against the
      hepatocellular carcinoma cell line (HepG2). METHODS: This study was performed in
      China Medical University Shenyang, China from September 2007-February 2008. The
      design of the study was to modify DCs with GPC3 and to be used to activate human
      T cells and elicit a cell-mediated immune response against HepG2 in vitro. The
      GPC3 gene expression was identified by western blot and immunocytochemistry. The
      proliferation of responder cells and cytotoxicity against HepG2 were examined by
      water-soluble tetrazolium salt -1 and lactate dehydrogenase assay respectively.
      The interferon-y (IFN-y) secreted was detected by ELISA assay. RESULTS: Both
      Western blot and immunocytochemical analysis assured the validity of GPC3
      transfection. Glypican3 modified DCs were potent in inducing responder cells
      proliferation and IFN-y production. The cytotoxicity in the group of GPC3
      transfected DCs were (38.90+/-0.95%) at the ratio of effector cells/target cells
      E/T:100:1, 30.83+/-1.24% at the ratio of E/T:50:1, and 23.84+/-0.65% at the ratio
      of E/T:10:1, respectively (which is significant compared with other groups,
      p<0.001). And the GPC3 modified DCs showed ability to induce high specific
      cytotoxicity against HepG2 in vitro. CONCLUSION: The effector cells stimulated
      with DCs that were transfected with pEF-hGPC3 plasmid could effectively lyse GPC3
      expressing HepG2 cells, which suggested that those genetically engineered DCs
      have the potential to serve as novel vaccine for HCC.

PMID- 18813404
TI  - The protective effects of demethoxyviridine and 1-alpha-hydroxy-demethoxyviridine
      in the livers of male rats treated with diethylnitrosamine and 2
      acetylaminflourene.
AB  - OBJECTIVE: To determine the protective effects of a fungal metabolite of
      demethoxyviridine (DMV) and its derivative, 1-alpha-hydroxy-DMV in the livers of
      2-month-old male Spraque-Dawley rats treated with diethylnitrosamine (DEN) and 2
      acetylaminflourene (2-AAF). METHODS: This study was performed in the Department
      of Medical Biology, Faculty of Medicine, Eskisehir Osmangazi University,
      Eskisehir, Turkey from May 2006. Animals were divided into 10 groups. Those were
      the control, olive oil, dimethyl sulfoxide (DMSO), DMV, 1-alpha-hydroxy-DMV, DEN,
      2-AAF, DEN+2-AAF, DEN+2-AAF+DMV, and DEN+2-AAF+1-alpha-hydroxy-DMV-treated animal
      groups. The liver microsomes were prepared from rats and the levels of expression
      of cytochrome P450 1A2 (CYP1A2) enzymes were determined with western blot
      technique. The liver tissue slides were evaluated histopathologically with
      hematoxylin and eosin staining and immunohistochemically for Harvey-retrovirus
      associated DNA sequences (Ha-Ras), glutathione S- transferase (GST-p), and
      connexion-32 (Cx32) proteins. RESULTS: Notably, there were no appreciable
      differences in CYP1A2 level among control, olive oil, and DMSO-treated animals.
      The CYP1A2 level was significantly decreased in 2-AAF, DEN+2-AAF, DEN, DEN+2
      AAF+DMV, DEN+2-AAF+1-alpha-hydroxy-DMV, 1-alpha-hydroxy-DMV, and DMV-treated
      animals as compared to the control. Most prenoplastic focus was found in DEN+2
      AAF treated group. CONCLUSION: Demethoxyviridine and 1-alpha-hidroksi-DMV had
      protective effect in the livers of DEN, 2-AAF and DEN+2-AAF induced rats.

PMID- 18813405
TI  - Accessory sulci of the liver. An anatomical study with clinical implications.
AB  - OBJECTIVE: To study the presence of accessory sulcus (AS) in the embalmed
      cadaveric livers, and compare it with the normal liver. METHODS: The present
      study was conducted on 40 embalmed cadaveric livers in the Department of Anatomy,
      National University of Malaysia, Kuala Lumpur, Malaysia, from September to
      October 2007, in order to observe the presence and pattern of anomalous AS.
      RESULTS: Out of the 40 liver specimens studied, we observed the presence of AS in
      only 2 specimens 5%. The AS was located in the inferior and posterior surfaces of
      the right lobes in 2 specimens. CONCLUSION: The AS of the liver is a rare
      anomaly. Research studies had mainly described the diaphragmatic sulci in the
      liver, however there are no research reports on the presence of AS in the
      inferior surface of the right lobe of the liver. The presence of the AS may
      represent the deep course of the hepatic veins superficially, thus proving to be
      more beneficial to the hepatobiliary surgeons. The AS may be due to a
      developmental defect, or may be acquired as a result of pressure by any
      superficial structure. The precise anatomical knowledge of the AS may also be
      important for radiologists interpreting CT images of injected veins. The gross
      anatomical findings of anomalous AS in 2 liver specimens, and its clinical
      implications are being highlighted in the present study.

PMID- 18813406
TI  - Assessment of the direct agglutination test, fast agglutination screening test,
      and rK39 dipstick test for the sero-diagnosis of visceral leishmaniasis in Syria.
AB  - OBJECTIVE: To evaluate the performances of 3 serological assays (direct
      agglutination test [DAT], fast agglutination screening test [FAST], recombinant
      protein [rK39] dipstick) test for use in primary care, for the diagnosis visceral
      leishmaniasis (VL) in Syria. METHODS: We utilized 267 serum samples obtained
      during 2007 from patient groups confirmed and suspected VL, confirmed cutaneous
      leishmaniasis, toxoplasmosis from endemic areas in Syria and control samples, and
      applied the 3 serological tests in the Damascus University, Damascus and Health
      laboratories at the same time, on these samples. RESULTS: Our data show that the
      tests were very sensitive, where the DAT was the most specific followed by FAST,
      then rK39 dipstick. CONCLUSION: Our study confirmed that all the tests performed
      well, and proved to be very important sero-diagnosis tools for visceral
      leishmaniasis.

PMID- 18813407
TI  - Intramuscular ketamine for prevention of postanesthesia shivering in children.
AB  - OBJECTIVE: To compare the effects of intramuscular ketamine with pethidine and
      placebo on post operative shivering in children undergoing tonsillectomy.
      METHODS: A prospective randomized double-blind study was conducted at King
      Abdulaziz Naval Base Hospital, Jubail, Kingdom of Saudi Arabia, from November
      2006 to October 2007. One hundred and twenty children (American Society of
      Anesthesiologists Grade 1, aged 5-12 years) were enrolled. Children were randomly
      allocated to receive ketamine 1 mg/kg (group K, n=40), or pethidine 0.5 mg/kg
      (group P, n=40), or normal saline (group S, n=40) intramuscularly just after
      induction of general anesthesia. Hemodynamic parameters, oxygen saturation and
      tympanic temperature were measured and recorded before induction of anesthesia
      and at regular intervals thereafter. An investigator blinded to the treatment
      group, graded postoperative shivering using a 5 point scale. RESULTS: The number
      of patients shivering on arrival to the recovery room and at 10 and 20 minutes
      after operation were significantly less in groups K (1,1,1) than in group S
      (19,12,17). No patient that received pethidine shivered. The time to first
      analgesic requirement in group S was shorter than groups K and P (p=0.001).
      CONCLUSION: The study indicates that the use of a prophylactic low dose ketamine
      was found to be effective in preventing post anesthesia shivering in children
      undergoing tonsillectomy. Ketamine may have at least theoretical advantages over
      pethidine as regard respiratory depression, nausea, and vomiting.

PMID- 18813408
TI  - Botulinum toxin versus surgical sphincterotomy in females with chronic anal
      fissure.
AB  - OBJECTIVE: To compare the effectiveness and the morbidity of botulinum toxin
      (BTX) in the treatment of chronic anal fissure (CAF) versus the standard surgical
      sphincterotomy. METHODS: One hundred female patients with CAF were treated by
      either closed lateral sphincterotomy [surgical group (Group I, n=50 patients)] or
      BTX 40 IU [chemical group (Group II, n=50 patients)]. The study was conducted in
      the King Abdul-Aziz University Hospital, Jeddah, Kingdom of Saudi Arabia, over 3
      years between January 2004 and December 2006. RESULTS: The healing rate was 100%
      in surgical group with no recurrence on the period of 3 years follow up and one
      patient has partial permanent incontinence. While in chemical group the healing
      rate was 86% (p=0.006). Ten patients had transient incontinence (p=0.014). Seven
      patients had recurrence within 6 months 14% (p=0.006). CONCLUSION: We conclude
      that chemical sphincterotomy is safe, effective first line treatment in selected
      female patients with CAF.

PMID- 18813409
TI  - A comparison of different hemorrhoidectomy procedures.
AB  - OBJECTIVE: To evaluate the pain level, analgesic consumption, operation time,
      bleeding and early complications after open and closed hemorrhoidectomy using a
      harmonic scalpel (HS) and classical methods. METHODS: Between January 2005 and
      January 2006, 87 patients with grade III-IV hemorrhoids, admitted in General
      Surgery Clinic, Gulhane Military Medical Academy, Ankara, Turkey were enrolled in
      the study. They were randomized into open HS (n=22), closed HS (n=22), Miligan
      Morgan (n=22), and Ferguson (n=21) hemorrhoidectomy. Patients were evaluated for
      postoperative pain, painkiller consumption, bleeding and operation time. RESULTS:
      Bleeding volume was significantly lower in Groups I-II (p<0.001). Operation time
      was significantly shorter in Group I (p<0.001). Postoperative pain and pain at
      the time of first defecation, was significantly lower in Groups I-III (p<0.001)
      compared with the other 2 groups and lower during days 2-6 in Group I compared to
      the Group III (p<0.004). Visual Analogue Scale results were similar in Groups II
      and IV. Analgesic consumption in Groups I-III was significantly lower than Groups
      II-IV (p<0.001). Oral analgesic consumption during 2-5 postoperative days was
      lower in Group I than in Group III (p<0.007) and similar in closed
      hemorrhoidectomy group. CONCLUSION: The use of HS in hemorrhoidectomy reduces
      postoperative pain, analgesic consumption, operation time, and bleeding. Harmonic
      scalpel hemorrhoidectomy is an effective, comfortable, and safe procedure. Use of
      suture in hemorrhoidectomy is a major cause of postoperative pain.

PMID- 18813410
TI  - The predictive value of extensor grip test for the effectiveness of treatment for
      tennis elbow.
AB  - OBJECTIVE: To compare the effectiveness of 5 different modalities, and determine
      the usefulness of recently proposed extensor grip test (EGT) in predicting the
      response to treatment. METHODS: In a randomized controlled clinical trial, 92 of
      98 tennis elbow patients in Sina Hospital Tehran, Iran between 2006 and 2007
      fulfilled the trial entry criteria. Among these patients 56 (60.9%) had positive
      EGT result. The stratified EGT result, were randomly allocated to 5 treatment
      groups: brace, physiotherapy, brace plus physiotherapy, injection, and injection
      plus physiotherapy. RESULTS: Patients with a positive EGT result had better
      response to treatments. Among them, injection plus physiotherapy was the most
      successful, then brace plus physiotherapy, physiotherapy, and brace injection was
      the worst treatment modality. Response to treatment was comparable in all groups
      between EGT positive and negative patients except bracing, in which positive EGT
      was correlated with a dramatic response to treatment. CONCLUSION: In all
      patients, injection plus physiotherapy and then brace plus physiotherapy is
      recommended, but in EGT negatives, bracing seems to be of no use. Injection alone
      is not recommended in either group.

PMID- 18813411
TI  - The effects of zinc supplementation on serum zinc, alkaline phosphatase activity
      and fracture healing of bones.
AB  - OBJECTIVE: To determine the effect of zinc supplementation on callus formation,
      serum zinc and alkaline phosphatase activity in humans. METHODS: This randomized,
      double-blind, placebo controlled clinical trial was conducted on 60 patients with
      traumatic bone fracture referred to Shohada Hospital of Tabriz, Iran from August
      to December 2007. Subjects were randomly divided into 2 groups: cases (n=30),
      receiving one capsule of zinc sulfate consists of 50 mg zinc each day and the
      controls (n=30), receiving placebo for 60 days. Individual and clinical
      information was determined by a questionnaire: nutritional intake by 3 days food
      records at the beginning and the end of trial. Serum zinc and alkaline
      phosphatase was measured by atomic absorption spectroscopy, and by enzymatic
      method. Callus formation during fracture healing was evaluated by radiography of
      the bone. RESULTS: There was no significant difference in physical activity,
      gender, age, type of fractures, and nutrient intake, between the 2 groups. The
      administration of zinc caused a significant elevation of serum zinc and alkaline
      phosphatase activity. Assessment of bone x- rays showed a significant progress in
      callus formation in cases compared to the controls. CONCLUSION: This study shows
      that zinc supplementation can stimulate fracture healing, however, it needs
      further study.

PMID- 18813412
TI  - Investigation of the effect of ginger on the lipid levels. A double blind
      controlled clinical trial.
AB  - OBJECTIVE: To study the effect of fine powder of ginger on lipid level in
      volunteer patients. METHODS: This is a double blind controlled clinical trial
      study in 2 cardiac clinics Cardiac Disease Clinic, Babol, north of Iran, between
      April to May 2004. We randomly divided the patients with hyperlipidemia into 2
      groups, treatment group (receiving ginger capsules 3 g/day in 3 divided doses)
      and placebo group (lactose capsule 3 g/day in 3 divided doses) for 45 days. All
      subjects with diabetes mellitus, hypothyroidism, nephrotic syndrome, and alcohol
      drinking, pregnancy and peptic ulcer were excluded. Lipid concentrations profile
      before and after treatment was measured by enzymatic assay. RESULTS: Forty-five
      patients in the treatment group and 40 patients in placebo group participated in
      this study. There was a significant reduce in triglyceride, cholesterol, low
      density lipoprotein (LDL), very low density lipoprotein (VLDL), levels of before
      and after study separately in each group (p<0.05). Mean changes in triglyceride
      and cholesterol levels of ginger group were significantly higher than placebo
      group (p<0.05). Mean reduction in LDL level and increase in high density
      lipoprotein level of ginger group were higher than the placebo group, but in VLDL
      level of placebo was higher than ginger (p>0.05). CONCLUSION: The results show
      that ginger has a significant lipid lowering effect compared to placebo.

PMID- 18813413
TI  - Prevalence of type 1 diabetes mellitus in Saudi Arabian children and adolescents.
AB  - OBJECTIVE: To determine the prevalence of type 1 diabetes mellitus among 0-19
      years old Saudi children and adolescents. METHODS: A nationwide Saudi Arabian
      project was conducted in the years 2001-2007 with the objective of establishing
      national growth charts, and defining the prevalence of some chronic childhood
      diseases such as diabetes mellitus. The 14,000 households were randomly selected
      based on a recent population statistic. The questionnaire used included
      demographic data and evidence of diabetes mellitus. The prevalence was estimated
      and expressed per 100,000. Breakdown of this figure per age and region was
      carried out. RESULTS: In the 11,874 out of the 14,000 84.9% selected households,
      45,682 children and adolescents were surveyed. Fifty children and adolescents
      were identified to have type 1 diabetes mellitus with a prevalence rate of 109.5
      per 100,000. The male to female ratio was almost equal (26 males and 24 females).
      The distribution of prevalence of type 1 diabetes mellitus by region shows that
      the highest was 162 in the central region, and the lowest was 48 in the eastern
      region. Children and adolescents were also grouped by age into 5-6 (prevalence
      100), 7-12 (prevalence 109), 13-16 (prevalence 243), and 17-18 (prevalence 150).
      CONCLUSION: We conclude that the prevalence of type 1 diabetes mellitus in Saudi
      Arabian children and adolescents is 109.5 per 100,000.

PMID- 18813414
TI  - Coagulation profiles in hypothyroid and hyperthyroid female patients in Sudan.
AB  - OBJECTIVE: To evaluate disturbances in the coagulation system in female patients
      with thyroid disorders in order to assess the effects of thyroid diseases on
      coagulation parameters. METHODS: This study was conducted in Khartoum state, the
      national capital of Sudan from February 2007 and February 2008 The study included
      30 patients with clinical hypothyroidism, and 30 patients with sub- clinical
      hypothyroidism (21 of them were recruited before starting the treatment). Also,
      the study included 30 patients with clinical hyperthyroidism, 30 with sub
      clinical hyperthyroidism, (37 of them were recruited before starting the
      treatment) and 30 normal individuals as the control group. Prothrombin time (PT),
      activated partial thromboplastin time, fibrinogen level, and platelets count were
      performed in patients and control samples. RESULTS: A significantly decrease in
      PT was observed in hypothyroid patients, and hyperthyroid patients compared to
      the control group. Activated thromboplastin time was significantly decreased only
      in hyperthyroid patients, compared to the control group. Moreover, fibrinogen
      level was significantly increased in hyperthyroid patients compared to
      hypothyroid patients. CONCLUSION: The study concluded that minor coagulation
      abnormalities were observed in both subclinical hypo- and hyperthyroidism
      compared to clinical hypo- and hyperthyroidism. Platelets count was also slightly
      decreased in both types of the disease. There was no significant effect of the
      treatment and age of such patients on the measured parameters. The study
      recommended to screen female patients with hypo- and hyperthyroidism for
      coagulation defect, to avoid the risk of such complications.

PMID- 18813415
TI  - Prevalence and intensity of hyperglycemia in non-diabetic patients undergoing
      coronary artery bypass graft surgery with and without cardiopulmonary bypass.
AB  - OBJECTIVE: To study the prevalence and severity of hyperglycemia in nondiabetic
      patients undergoing cardiac operation. METHODS: In an observational prospective
      study, 282 non-diabetic patients underwent elective off-pump (n=101) or on-pump
      (n=181) coronary artery bypass grafting (CABG) surgery from March 2006 to July
      2007 in Madani Heart Hospital, Tabriz, Iran. Blood glucose (BG) levels were
      measured during and 24 hours after operation. Frequencies of hyperglycemia
      (BG>or=126 mg/dl) and severe hyperglycemia (BG>or=180 mg/dl) and postoperative
      complications were compared in the 2 study groups. RESULTS: Prevalence of at
      least one episode of severe hyperglycemia was 54.6% (154/282) in our patients
      during, and 24 hours after operation. Intra-operative hyperglycemia was slightly
      higher in on-pump group. Frequency of post-operative hyperglycemia was higher,
      although not significantly different between the 2 groups. The 2 study groups
      were not significantly different in frequency of severe hyperglycemia during
      operation, although were different within 24 hours postoperative period.
      CONCLUSION: Prevalence of hyperglycemia especially severe hyperglycemia was high
      during, and after operation in both off-pump and on-pump CABG in non-diabetic
      patients. There was a borderline difference in blood glucose level between on
      pump and off-pump CABG patients. It may be prudent to consider glycemic control
      protocols in these patients especially in early post-operative period.

PMID- 18813416
TI  - Impact of metabolic syndrome's components on the development of cardiovascular
      disease in a Jordanian cohort with metabolic syndrome.
AB  - OBJECTIVE: To assess the gender differences in the prevalence of diabetes,
      composite cardiovascular disease, and the components of metabolic syndrome (MS)
      in a Jordanian cohort with MS. Secondly, to evaluate the impact of number of MS
      components on prevalence of diabetes, ischemic heart disease (IHD), and stroke.
      METHODS: We carried out a cohort study among participants who fulfilled the
      National Cholesterol Education Program (Adult Treatment Panel III) criteria for
      MS recruited from December 2006-2007 from Endocrine Outpatient Clinics of the
      King Hussein Medical Centre, Amman, and Prince Rashid Military Hospital, Irbid,
      Jordan. Patients were divided into groups according to gender, presence, or
      absence of diabetes, and were evaluated for MS components, presence of IHD, and
      stroke. RESULTS: Three hundred and fifty-seven patients 207 males and 150 females
      were included, type 2 diabetes was present in 226 (132 males) patients. No
      intergroup differences were found on waist circumference, systolic blood
      pressure, diastolic blood pressure, or fasting blood sugar. Female group was
      having a worst lipid profile, higher triglyceride levels and low high density
      lipoprotein. Metabolic syndrome components were more in males. Diabetic males
      have more composite cardiovascular disease (CCVD) [relative risk (RR)=1.88, 95%
      confidence interval: 1.01-3.59]. No difference in prevalence of CCVD between
      female subgroups neither between the 2 genders with MS. The prevalence of
      diabetes mellitus, IHD, and stroke increased with increasing number of MS
      components. Diabetes was the strongest predictor for development of CCVD (RR=1.8)
      and IHD (RR=2.18). CONCLUSION: Females with MS have the worst lipid profile
      compared to the males, diabetic males have the worst CCVD end point. The
      prevalence of diabetes and IHD correlates with the number of MS components.

PMID- 18813417
TI  - Knowledge and attitudes towards cardiopulmonary resuscitation among university
      students in Riyadh, Saudi Arabia.
AB  - OBJECTIVE: To assess the knowledge and attitudes towards cardiopulmonary
      resuscitation (CPR) among the students of King Saud University. METHODS: This
      study was a cross-sectional survey among King Saud University students, Riyadh,
      Kingdom of Saudi Arabia, which took place on December 17-20, 2006. The data was
      collected via self-administered questionnaires prepared in Arabic. The
      questionnaires were distributed to all 15 colleges of the University. RESULTS:
      Out of a study sample of 2250 students, 31% did not have prior CPR information.
      Of those with previous knowledge, 85% feel that it is inadequate. The most common
      sources of information were television and movies. The 12.7% of individuals
      encountered a situation that required the use of CPR. However, only 14% of them
      performed it. This was mostly due to lack of knowledge (48.2%). Eighty eight
      percent of students would like to learn how to perform CPR. Out of all King Saud
      University students, 45% believe that CPR training should be a graduation
      requirement. CONCLUSION: It was found that the overall attitude towards CPR was
      positive. However, the knowledge on the topic was insufficient. Thus, more focus
      should be placed on the improvement of CPR skills. In addition, more studies are
      needed to assess knowledge and attitudes towards CPR in the community.

PMID- 18813418
TI  - Splenectomized versus non-splenectomized patients with thalassemia major.
      Echocardiographic comparison.
AB  - OBJECTIVE: To study the effect of splenectomy in patients with thalassemia major
      on the cardiovascular system through echocardiographic study. METHODS: A
      prospective, cross sectional study was carried out from December 2006 to December
      2007. Patients from the Thalassemia Center in the Maternity and Children's
      Hospital, Madina, Kingdom of Saudi Arabia, were screened by means of history,
      physical examination, laboratory studies, and echocardiography. RESULTS: Fifty
      seven patients were studied: 36 were non-splenectomized, while 21 were surgically
      splenectomized. The 2 study groups were well matched for age, gender, height, and
      weight. The total amount of blood given during the previous year (6577.1+/-206.9
      ml versus 5390.5+/-220.2 ml, p=0.0005), and the annual transfusion index (200.9+/
      11.3 versus 134.1+/-7.3, p=0.0001) were significantly lower in the splenectomized
      group. There was no significant difference between the 2 groups regarding
      laboratory studies. Left ventricular systolic function shows no difference
      regarding fraction shortening between the 2 groups. The mitral valve E/A ratio
      was significantly higher in the splenectomized group (1.6+/-0.2 versus 1.4+/-0.2,
      p=0.02). The pulmonary artery pressure was higher in the splenectomized group
      (34.2+/-9.1 versus 20.8+/-9.2 mm Hg, p=0.0001). There was a significantly higher
      number of patients with pulmonary hypertension in the splenectomized group (14
      [66.7%] versus 6 [16.7%], p=0.0004). CONCLUSION: Splenectomized patients with
      thalassemia major are at high risk of having impaired diastolic left ventricular
      function and pulmonary hypertension.

PMID- 18813419
TI  - Comparison of hysterosalpingography and laparoscopy in the evaluation of
      infertile women.
AB  - OBJECTIVE: To compare tuboperitoneal factors of infertile women by
      hysterosalpingography (HSG) and laparoscopy. METHODS: In this cohort study, 82
      infertile cases were evaluated retrospectively by laparoscopy, 3 months
      subsequent to HSG in the Department of Gynecology and Obstetrics, Medical School
      of Dicle University, Diyarbakir, Turkey, between March 2004 and April 2006. The
      findings of HSG and laparoscopy were compared. RESULTS: Out of the 82 infertile
      women, pathological findings were observed in 45.1% by HSG, and 54.9% had no
      pathological finding. On laparoscopic evaluation, however, pathological findings
      were observed in 65.85%, and 34.15% had no pathological findings. The
      pathological findings were detected by laparoscopy in 20 of the 45(44.4%)
      patients who had no pathological findings by HSG, and no pathological findings
      were detected by laparoscopy in 3 of the 37 (8.1%) patients who had pathological
      findings by HSG. Laparoscopy revealed no pathological findings in 6 of the 35
      patients who had tubal pathology by HSG. The sensitivity of HSG was 63%,
      specificity was 89.3%, and the positive predictive value was 92%, with a 55%
      predictive value, and the accuracy ratio was 72%. CONCLUSION: Laparoscopy is a
      superior method for the research of tubal and pelvic pathologies in the
      evaluation of infertility. However, HSG is a more economical and elementary
      method suitable for evaluation of endometrial and tubal pathologies, and
      laparoscopy is an appropriate method for examining the external part of tubae,
      fimbriae, the relation of tuba and ovary, endometriosis, adhesions, tuberculosis,
      and other pathologies. Therefore, these 2 methods are not alternative, but
      complementary.

PMID- 18813420
TI  - Overweight and obesity in the eastern province of Saudi Arabia.
AB  - OBJECTIVE: To describe anthropometric characteristics of participants and the
      influence of sociodemographic and cardiovascular risk factors involved in the
      prevalence of obesity in the eastern province of Saudi Arabia. METHODS: In the
      year 2004, all Saudi residents in the Eastern province aged 30 years and above,
      were invited to participate in a community screening campaign for early detection
      of diabetes and hypertension. Demographic data, medical history, life habits,
      weight, height, blood pressure, and glucose concentration were recorded using a
      structured questionnaire. Obesity and overweight were defined by body mass index
      (BMI) >or=30 kg/m2 and 25-29.9 kg/m2, respectively. Logistic regression was used
      to predict the association of the significant factors with the prevalence of
      obesity. RESULTS: Out of 195,874 participants, the overall prevalence of obesity
      was 43.8%, while 35.1% were overweight. The prevalence of underweight was 1.3%.
      The peak prevalence of obesity was observed in the age group 50-59 years. Obesity
      was higher among women than men, higher in housewives, and among the less
      educated than others (p<0.0001). Linear regression analysis showed a strong
      proportional association of BMI with diabetes, hypertension, triglycerides and
      cholesterol, and an inverse proportional association with physical activity and
      smoking CONCLUSION: Obesity and overweight constitute an important health problem
      affecting a high proportion of Saudi population. Addressing associated factors,
      and enhancing public health education is an important aim to focus on for weight
      control.

PMID- 18813421
TI  - Prevalence of vitamin-mineral supplement use among Jordan University students.
AB  - OBJECTIVE: To determine the prevalence, reasons, source of information of vitamin
      mineral supplement uses, and their relationship with selected demographic and
      lifestyle characteristics among Jordan University students. METHODS: A cross
      sectional survey was carried out at Jordan University, Amman, Jordan from March
      to September 2005. The survey included 1,187 students aged 17-28 years. A
      multistage stratified sampling technique was used to recruit the participants
      from different majors at Jordan University. A self-administered questionnaire
      containing questions on use of vitamin-mineral supplement during the last year,
      demographic, and lifestyle characteristics was completed. RESULTS: The overall
      prevalence of vitamin-mineral supplement use during the last year reported by
      students was 27.4% (males 22%, and females 30.2%). Vitamin-mineral supplement use
      among university students was significantly (p<0.05) associated with age, gender,
      family monthly income, smoking status, physical activity, vegetarian status, and
      body mass index. The most frequently used supplements were multivitamins (10.4%)
      and multivitamins-multi minerals (10%). The most frequently given reason for
      supplement use was for treatment. The main frequently reported source of
      information was a physician (45.8%). CONCLUSION: The overall prevalence rate of
      vitamin-mineral supplement use is very low. Supplement users are more likely to
      be: females, nonsmokers, of higher income, physically active, vegetarians, and of
      normal body mass index. The main reason for supplement use is for treatment, and
      the major source of information on supplements is by physicians and pharmacists.

PMID- 18813422
TI  - Oral hygiene awareness among female Saudi school children.
AB  - OBJECTIVE: To evaluate the oral hygiene habits and utilization of professional
      dental health services by all the children in the primary schools, and to compare
      the differences in oral hygiene awareness (OHA) and dental health status of
      schoolchildren who are exposed to dental health education and those who are not.
      METHODS: Participants included 400 Saudi children, randomly selected from the
      primary female schools in Al-Kharj, Kingdom of Saudi Arabia on April 2007. Two
      hundreds children (age 9-11) from the 25 schools, who were exposed to the dental
      health education program on April 2006, were randomly selected as the study
      group. Two hundred children (age 9-11) from the schools, which were not exposed
      to such program were also randomly selected as the control group. The required
      information about oral hygiene awareness was collected through an especially
      designed questionnaire. RESULTS: Tooth brushing for 2 times a day or after meals
      were more common among schoolchildren of study group, than schoolchildren of
      control group. A significant difference (p=0.00) was observed between study group
      and control group, with regard to never brush their teeth. There was no
      significant difference between study group and control group with respect to
      using dental floss, using mouthwash, and in relation to never visiting a dentist
      for check up. The main reason cited by study group, and by control group for
      visiting the dentist was that they had severe toothache. Both groups presently
      consume more sweetened soft drinks. A significant (p=0.00) higher frequency of
      good dental status was observed in the study group, as compared with that of the
      control group. CONCLUSION: The school which applied this program, showed improved
      OHA of children as compared with the control group. Systematic school-based oral
      health promotion programs are urgently needed in the Kingdom to target lifestyles
      and health needs of children.

PMID- 18813423
TI  - Townes-Brocks syndrome. A neonate with extended spectrum and thrombocytopenia.
AB  - Townes-Brocks syndrome is a rare malformation syndrome characterized by thumb,
      auricular, renal, and anal anomalies. Both familial and isolated cases with
      clinical heterogeneity were reported in the medical literature. We present a
      sporadic case with typical clinical features and extended spectrum, that has
      previously not been described. Left sided facial palsy, external auditory canal
      atresia, club hand with radius aplasia, bilateral clubfoot, and sacral skin tag
      were the additional findings. Isolated patent ductus arteriosus was the
      associated congenital heart defect. Thrombocytopenia was another documented
      hematological abnormality.

PMID- 18813424
TI  - An incidental coexistence of Mayer-Rokitansky-Kuster-Hauser syndrome with pelvic
      ectopic kidney and perirenal endometrioma.
AB  - In this case report, a Mayer-Rokitansky-Kuster-Hauser syndrome with pelvic
      ectopic kidney and a perirenal cyst with endometrial tissue inside is
      demonstrated. A 17 year old patient admitted with primary amenorrhea. Pubertal
      stages were completed. In pelvic ultrasonography; uterus could not be detected, a
      6 x 11 cm sized cystic lesion was seen on the right adnexal area. A centrally
      located 5.5 x 9 cm sized ectopic pelvic kidney was detected. Hormones and tumor
      markers were normal. Laparoscopy was planned. In the laparoscopic observation,
      uterus and both tubes could not be detected, ovaries were normal. There was a 6 x
      7 cm sized cyst located in the retroperitoneal area, the origin of the cyst could
      not be identified. Laparatomy was considered, retroperitoneal space was entered,
      an 8 x 11 cm sized smooth contoured perirenal cyst adjacent to the pelvic kidney
      was detected. Cyst was extirpated. The pathology result was reported to include
      endometrial tissue and hemorrhage inside.

PMID- 18813425
TI  - Unusual case of accessory nose associated with unilateral complete congenital
      choanal atresia.
AB  - We report here an extremely rare and unusual case of accessory nose associated
      with unilateral complete congenital choanal atresia. Although other types of
      nasal congenital nasal anomalies are not rare, however, extreme rarity of nose
      duplication is worth reporting, as it is an extremely rare type of nasal
      congenital deformity.

PMID- 18813426
TI  - Severe hepatic dysfunction after sevoflurane exposure.
AB  - Sevoflurane is thought to have a potential for hepatotoxicity. A few cases of
      hepatotoxicity have been reported since it was introduced in 1990 into clinical
      practice in Japan. The underlying pathophysiology of hepatotoxicity is
      nonspecific. We report a case of severe hepatic dysfunction after uneventful
      sevoflurane anesthesia in a child with posterior fossa resection of
      medulloblastoma. The case of sevoflurane being incriminated is unclear due to
      various confounding factors that is worthy of discussion.

PMID- 18813427
TI  - Epidermoid cyst of the spleen.

PMID- 18813428
TI  - The importance of CD10 and h-Caldesmon in the distinction of smooth muscle tumors
      of the uterus and endometrial stromal sarcoma.

PMID- 18813429
TI  - Effects of walnut leaf aqueous extract on blood sugar and lipids in male diabetic
      rats.

PMID- 18813431
TI  - Effect of intraoperative mitomycin C application on recurrence of endoscopic
      dacryocystorhinostomy.

PMID- 18813430
TI  - Association between tryptophan hydroxylase gene polymorphism and painful non
      osseous temporomandibular disorders.

PMID- 18813432
TI  - Kohler's disease.

PMID- 18813433
TI  - Al-Nafis and Servetus.

PMID- 18813434
TI  - Arthroscopic surgery and osteoarthritis of knee.

PMID- 18813435
TI  - Drug use evaluation of antibiotics prescribed in a Jordanian Hospital outpatient
      and emergency clinics using WHO prescribing indicators.

PMID- 18813436
TI  - Henoch-Schonlein purpura in children. Influence of age on the incidence of
      nephritis and arthritis.

PMID- 18813437
TI  - Henoch-Schonlein purpura in children. Influence of age on the incidence of
      nephritis and arthritis.

PMID- 18813438
TI  - Henoch-Schonlein purpura in children. Influence of age on the incidence of
      nephritis and arthritis.

PMID- 18813440
TI  - [Mistreatment in childhood and adolescence: an overview of personal and
      collective prevention and intervention mechanisms].

PMID- 18813439
TI  - [Personal and collective mechanisms for protecting and enhancing the quality of
      life during childhood and adolescence].
AB  - Based on recent literature, this paper presents individual and collective
      strategies for protecting and promoting the quality of life during childhood and
      adolescence. Addressing the core principles of an all-round protection policy
      aligned with the Universal Declaration of Human Rights and the Children's and
      Adolescents' Statute, it also encompasses practical aspects of professional
      approaches to children and adolescents in terms of ethics and confidentiality.
      Additionally, it discusses the determining factors that shape the development of
      individual and collective resilience, on scientific and theoretical bases, in
      addition to risk factors, health protection and the cognitive and psychosocial
      development of this segment of the population.The roles played by adults are
      stressed as protection factors in the macro and micro environments, especially
      the roles assigned to family members and other adults in the social surroundings
      such as healthcare practitioners those engaged with education, social welfare and
      mental health. The important role played by Social Networks is stressed, as a key
      strategy for implementing inter-disciplinary and trans-sector practices designed
      to enhance well-being and quality of life throughout the entire community.

PMID- 18813441
TI  - [Obstacles hampering health promotion programs and schemes for preventing harm
      caused by violence among adolescents].

PMID- 18813442
TI  - [Dealing with the sexual exploitation of children and adolescents: challenges and
      paths].

PMID- 18813443
TI  - [Drug use among young adolescents: prospects for prevention within the context of
      family relationships and education in the light of damage control principles and
      practices].

PMID- 18813444
TI  - [The role of the family: outlook for personal and collective mechanisms for
      promoting the health of young people].

PMID- 18813445
TI  - [Psychological mistreatment of children: current controversies and challenges for
      research and practice].

PMID- 18813447
TI  - [The profile of violence against children and adolescents according to Child
      Protection Council records: victims, aggressors and patterns of violence].
AB  - OBJECTIVE: To estimate the prevalence of violence against children and
      adolescents through the records of Child Protection Councils, associating this
      violence with the age of the victims and their links with the aggressor. METHOD:
      Data were collected from the records and the prevalence rates were calculated
      through the Prevalence Ratio (PR), together with the associations among
      variables, with a critical level of 5%. RESULTS: Out of 1,293 records of
      violence, 1,011 (78.1%), originated in the home. The most frequent types of
      violence were: neglect (727), failure to provide basic care (304) and abandonment
      (259); physical violence (455), beatings (392) between 2 and 13 years old;
      psychological violence (374) through threats (219); sexual violence (68) through
      abuse (58), mainly among adolescents. Denunciations were mainly (398) anonymous
      (30.8%); the aggressors through neglect were the parents; through physical
      violence, the stepmother and "other aggressors"; through sexual violence, the
      stepfather and "other relatives / aggressors"; psychological violence was
      prevalent among all aggressor categories. CONCLUSIONS: The findings indicate the
      need to extend the Anti-Violence Hot-line facilities, training Council Members in
      terms of keeping proper records, and implementing policies designed to prevent
      violence against children and adolescents.

PMID- 18813448
TI  - [Experimentation and regular use of alcoholic beverages, cigarettes and other
      Psychoactive Substances (PAS) during adolescence].
AB  - OBJECTIVE: To analyze the use of alcoholic beverages, cigarettes, other
      psychoactive substances - PAS , among adolescents of public schools of Feira de
      Santana, Bahia/Brazil. METHOD: Cross sectional study with random samples,
      stratified in terms of conglomerate units (schools and students). The sample of
      the study totalled 1,409 adolescents between 14 and 19 years old from 10 public
      schools; 30% of the total of schools of the municipality with
      500,000/inhabitants. The representation of schools and students was respected.
      The self-report instrument was elaborated according to OMS recommendations and as
      used in others studies. The data were collected according to guaranteed the
      anonymity of the subjects investigated. RESULTS: 86,5% of the adolescents were
      considered well informed on PAS; 57,0% reported alcoholic beverage consumption,
      mainly beers and wines; 23,3% used cigarettes and 5.2% other PAS (marijuana,
      solvents and cocaine); 29,3% reported drinking alcoholic beverages one to three
      times/month and 13% every weekend. Among subjects 10 to 14 years old, 47%
      reported drinking alcohol and 16.7% using other PAS. The statistics analysis
      showed that consumption of alcohol, cigarettes and other PAS is significantly
      higher among 17-19 years males. Interestingly, the main motivation for drug use
      is the company of friends and parents. CONCLUSIONS: implement of a drug
      prevention program's in schools.

PMID- 18813450
TI  - [A person-process-context study of the quality of interactions between the
      teenage mother and her baby].
AB  - OBJECTIVE: To understand the transmission mechanisms of psychosocial difficulties
      prompted by teenage mother and baby interactions. The hypothesis is that the
      quality of the mother-child exchanges relies on linked with the characteristics
      of the mother, such as being abused and poor preparation for motherhood, as well
      as the characteristics of the child. METHOD: Direct observation of the quality of
      exchanges between 97 primipara adolescents and their four month old babies. The
      teens were 13-18 years old, in the 26th week of pregnancy, from four homes run by
      the Youth Center in Montreal and Rosalie-Jette School. They completed
      questionnaires on their preparation for motherhood and histories of emotional
      abuse. RESULTS: The lack of knowledge (during pregnancy) on the development and
      types of care needed by babies is linked with insensitive maternal exchanges with
      the four month old child. An interactive effect was seen between the
      characteristics of the mother and baby. CONCLUSION: The interaction between the
      characteristics of the mother and her baby may trigger a negative feedback cycle
      that will hamper harmonious interpersonal relationships to an increasing extent
      over time, noted most frequently when the partners react to adversity, being less
      able to soothe the exchanges.

PMID- 18813449
TI  - [Oral health among adolescents: aspects relating to hygiene, dental cavities and
      periodontal disease in the cities of Recife and Feira de Santana, Brazil].
AB  - OBJECTIVE: To characterize the oral health in adolescents in the cities of Recife
      and Feira de Santana, Northeast Brazil by assessment of personal hygiene and
      dental cavities and periodontal disease. METHOD: Forty adolescents between ten
      and eighteen years old were assessed through an exploratory study run in Recife
      in 2005. In Feira de Santana, 971 adolescents (twelve years old) were examined
      through a cross section study in 2002. It was assessed cavity status through the
      number of cavitied, missing and filled teeth, visible dental plaque, bleeding
      gums and periodontal status. The analysis was based on Chi-Square, Kruskall
      Wallis and Fisher tests, with a confidence interval of 95%. RESULTS: The most of
      adolescents followed oral hygiene practices three times a day. The DMTF values
      presented a median of 1.5 in Recife and averages of 1.89 in state schools, 2.17
      in municipal schools and 2.39 in private schools in Feira de Santana. The
      bleeding gum in Recife presented a median of 27%, and in Feira de Santana the
      healthy sextant averages of 4.36, 4.08 and 5.16 in state, municipal and private
      schools respectively. CONCLUSION: The frequency of the dental cavities was low,
      with most of the adolescents reporting good habits of oral hygiene and favorable
      periodontal conditions.

PMID- 18813451
TI  - [Caring for the health of young children in the family context: an ethnographic
      study of low income families].
AB  - This study examines ways of caring for the health of small children in families
      assisted by the Family Health Program in a low-income outlying district of
      Salvador over a period of nine months. Based on participant observations
      supplemented by semi-structured interviews, the ethnographic approach offers a
      close-up view of how the respondents understand childcare and its links to the
      social and cultural context. Childcare requirements are arrayed along three main
      axes, structured on the basis of the child's gender: preservation of integrity,
      ability to play and education. Practices related to healthcare express
      evaluations and decisions that take into consideration the constraints imposed by
      reality and different standpoints, with the medical view occupying an important
      but not preponderant - position. Finally, the inter-subjective character of
      childcare is examined, in the sense that adults obtain moral gratification
      through caring for children, striving to meet their needs.

PMID- 18813452
TI  - [Adolescents in conflict with the law].
AB  - This study is focused on teenagers who behave violently and who are also victims
      of violence. The data was collected from records of adolescent inmates in Sao
      Jose do Rio Preto. The variables selected were: place of residence, age,
      education level, type of offense, drugs use, family income, parent education
      levels, jobs. The findings disclose a social and demographic profile for
      teenagers around seventeen years old with only elementary education. The most
      common offence was robbery; followed by theft, homicide, drug dealing, and
      robbery leading to death. Most of these teenagers smoked tobacco and marijuana,
      drank alcoholic beverages and took crack. The data indicate a context defined by
      precarious living conditions where family members have low incomes and poor job
      skills, together with alcohol abuse. As a result, they help turn teenagers into
      victims of society. The mother - who typically supports the household - is the
      strongest presence during the incarceration period, serving as a mediator between
      the adolescent in conflict with the law, the courts and the community. In view of
      the high costs of interpersonal violence, it is necessary to develop and
      implement a municipal strategy for children and adolescents in Sao Jose do Rio
      Preto.

PMID- 18813454
TI  - [Abortion and miscarriage in adolescence: an epidemiological study].
AB  - This study was conducted at the Santa Izabel Maternity Hospital in the town of
      Bauru, Sao Paulo State, Brazil, in order to investigate abortions and
      miscarriages in adolescence, comparing them to terminations among adult women.
      The indicators are used to draw up an epidemiological profile of hospitalized
      women through data collected from documents on women with diagnoses of abortion
      or miscarriage from 2000 to 2003, regardless of their clinical form. The total
      number of registered early terminations of pregnancy reached 2,286, with 459
      (20.08%) during adolescence, with the complete form being significantly higher
      among teenagers than adults; a decrease in the occurrence among adolescents was
      noted, dropping from 30.5% in 2000 to 25.05% in 2001, 23.53% in 2002 and 20.92%
      in 2003; with adolescents tending to remain in hospital for two or more days. The
      implementation is stressed of policies and programs addressing sexual and
      reproductive health and its co-morbidities.

PMID- 18813453
TI  - [Violence against adolescents: differentials by gender and living conditions
      strata].
AB  - An ecological study was conducted in order to analyze differences in mortality
      rates among adolescents by gender and living conditions strata in Recife from1998
      to 2004. The average mortality coefficient for violence during this period was
      calculated by gender for the city and by living conditions strata. This analysis
      demonstrated a higher risk of death by violence for male adolescents in Stratum
      III (poorest living conditions). The mortality rates by violence for men and
      women were 10.89 (Recife); 10.90 (Stratum I); 11.70 (Stratum II) and 10.30
      (Stratum III). The findings show that although males are at the highest risk, it
      is also quite clear that living conditions influence the distribution of the
      mortality rate due to violence.

PMID- 18813455
TI  - [The contribution of vulnerability to determining the human development index:
      studying Santa Catarina State, Brazil].
AB  - The concept of Human Development is grounded on the assumption that progress
      should not be measured just in economic terms, but must also encompass other
      social, cultural and political characteristics. The purpose of this paper is to
      assess the relationship between vulnerability and human development, proposing an
      approach for attaining the fourth and fifth Millennium Goals, based on a study of
      municipalities in Santa Catarina State, Brazil. The data were taken from the
      Human Development Atlas published in Portuguese by the United Nations Development
      Programme (UNDP) in Brazil during 2000(1) and Brazilian Institute of Geography
      and Statistics - IBGE . After a superficial analysis of this State, all the
      municipalities were analyzed in greater detail through the Municipal Human
      Development Index (HDI-M) ratings for their vulnerability indicators and
      components. The HDI-M ratings were scored by vulnerability variables, described
      in quartiles for each HDI-M. The HDI proved useful for the general description of
      the conditions in this State and distinguishing groups of municipalities. When
      broken out into groups, some indicators showed significant inequalities.

PMID- 18813456
TI  - [Expectations of adolescents in relation to the changes of nutritional profile].
AB  - This article presents results of a research of nature quanti-qualitative on
      nutrition and adolescents of Centro Salesiano do Menor, located in Vitoria (ES).
      The aim of this study was to know the nutritional profile and expectations of the
      adolescents in relation the changes in the nutritional profile. Structured
      interview with subjective and objective questions was realized with 43
      adolescents 14 to 17 years old and collected anthropometric date to valuation of
      the state nutritional according to the body mass index (BMI). Fragments of the
      speeches were selected and transcripts in the text as form of briefing of the
      open answers. The majority (86%) was classified as eutrofica and had disclosed to
      dissatisfaction with the body and a great concern with the beauty. The results
      had evidenced the importance given to the aesthetic one, as the main reason to
      desire a corporal change. Difficulties had been told in what it says respect to
      the alimentary control and the accomplishment of physical activity. Feeling of
      discrimination of the society to that they do not correspond to the beauty
      standard appeared in the answers of the adolescents. One concludes that the
      adolescents present perception of its weight not have correspondence with the
      found results of BMI and low self-esteem, desiring changes.

PMID- 18813457
TI  - [Prevalence of cavities among adolescents in public and private schools in Joao
      Pessoa, Paraiba State, Brazil].
AB  - The purpose of this study was to ascertain the prevalence of cavities among
      adolescents in public and private schools in Joao Pessoa, Paraiba State, Brazil,
      comparing the DMFT in terms of gender and age, as well as education levels and
      quality among mothers in these two types of schools. The sample consisted of
      3,330 adolescents between twelve and fifteen years old: 1,665 attending public
      schools and 1,665 attending private schools. The DMFT was evaluated by the WHO
      criteria (1997), using the Kappa (0.92) intra-examiner agreement for cavity
      diagnoses and the Mann-Whitney and Kruskal-Wallis statistical analyses. The
      prevalence of cavities in public schools was 51.6%, compared to 9.3% in private
      schools. The DMFT for girls was 4.79 and 3.46 for boys in public schools
      (p<0.0001) and 2.11 and 1.65 (p=0.0007) in private schools. At the age of 12
      years, the DMFT was 3.37 in public schools and 1.35 in private schools, while for
      the age of 15 it was 5.65 and 2.88 for each type of school. Among children whose
      mothers graduated from high school, the average DMFT was 4.21 in public schools
      and 1.81 in private schools. The prevalence of cavities was higher among girls in
      public schools, increasing with age and decreasing with higher education levels
      among mothers.

PMID- 18813458
TI  - [Profile of public dental care for children and adolescents in Sao Luis, Maranhao
      State].
AB  - This profile of public dental care for children/adolescents in Sao Luis, Maranhao
      State, Brazil, is based on a survey conducted through interviews, designed to
      identify these services and help upgrade Health Services available in this city.
      It describes the pediatric dental care available and the age groups attended, the
      qualifications of the practitioners involved, the types of treatment for primary
      and permanent teeth and oral health education programs run at the Municipal
      Healthcare Units with dental facilities, analyzed through visits and structured
      interviews. The findings show that dental care was available for
      children/adolescents (mainly between 6 and 12 years old) at 91.1% of the
      Healthcare Units offering daily and universal care (65.75%), as well as at those
      whose services are limited to certain specialties and/or specific days (34.15%).
      All the public Healthcare Units offered surgical treatment for permanent teeth.
      Fillings are used more for permanent teeth than primary teeth. Among the public
      Healthcare Units, 25 (55.5%) did not offer or run oral health programs. At most
      (75.5%) of the Units visited, dental treatment for children and adolescents is
      limited to basic care and directed mainly to permanent teeth. The traditional
      welfare model of providing care as freely demanded remains in place.

PMID- 18813459
TI  - [Analysis of factors associated with non-acceptance of hepatitis B vaccine among
      low income adolescent students].
AB  - To evaluate the predictor factors for non-acceptance of hepatitis B vaccine among
      low-income adolescent students in the Goiania Metropolitan Region, Goias State,
      Brazil. In this study, 304 HBV-susceptible individuals enrolled in two schools
      were interviewed, and the HBV vaccine was offered. Only 195 (64%) of adolescents
      accepted the first dose of vaccine. On the other hand, 182/195 (93.3%) received
      the full HBV vaccine scheme. School factors played a role in vaccine acceptance,
      as School B and night classes were independently associated with non-acceptance
      of hepatitis B vaccination. The findings of this study ratify the low acceptance
      of hepatitis B vaccine among adolescents, highlighting the need for health
      education programs aiming at this group for hepatitis B vaccinations, while
      buttressing the importance of school-based vaccination strategies for attaining
      full HBV immunization of this target population.

PMID- 18813460
TI  - [Vitamin A deficiency among children in Brazil and worldwide].
AB  - Based on a ten-year literature review, this paper describes important aspects of
      Vitamin A Deficiency (VAD) among children in Brazil and worldwide. It presents
      VAD within a clinical and sub-clinical deficiency context, emphasizing this as a
      public health issue. VAD has been diagnosed in children from several parts of
      Brazil, especially in the Southeast and Northeast. Worldwide, the highest VAD
      prevalence is found in parts of parts of Africa: Mali, Ethiopia and Nigeria, and
      clinical indications noted especially in parts of Asia and Africa. However, no
      studies of clinical indications were located. Studies point to VAD as a public
      health issue among children, particularly in the poorest parts of the world.

PMID- 18813461
TI  - [Affective interactions with children in shelters: an ethnographic study].
AB  - This study was conducted in order to observe interactions among twenty children
      living in a sheltered home and their care-givers. Using ethnographic methodology,
      these children (between ten months and five years old) were observed during half
      hour meetings held twice a week for three and a half months. The findings
      indicate a lack of training among the care-givers, reflected in verbal hostility
      towards the children, with limited care, few words of encouragement and little
      physical contact. At the same time, it was noted that the children searched
      continuously for attention and care from other adults visiting the home. This
      underscores the need to prevent and restructure poor relationships between care
      givers and children, shaping healthy environment for their development.

PMID- 18813462
TI  - [The standpoint of healthcare practitioners on the promotion of play in
      hospitals].
AB  - This study examines and analyzes the limits and possibilities of the promoting
      play in hospitals. This investigation can contribute to the collective health
      field, as discussions about the views of healthcare practitioners on promoting
      play in hospitals may well influence the development of new childcare models.
      This discussion is grounded on a qualitative approach to the dynamics of
      relationships and the role of play in a hospital setting. Drawn from interviews
      with 33 practitioners from three hospitals located in different parts of Brazil,
      the data analysis is based on linking up issues that emerge from their comments,
      together with theoretical references. In terms of findings, the acknowledgment of
      this type of intervention by the institution could facilitate or complicate these
      actions. The conclusions clearly indicate that assigning play promotion the
      status of a therapeutic tool within a healthcare environment may subvert the
      rules and hierarchies of the institution.

PMID- 18813463
TI  - [Home technological support network for technology-dependent children discharged
      from a state-run hospital].
AB  - Due to major advances, life maintenance technology has improved remarkably over
      the past few years. Research and development in the field of intensive pediatric
      and neonatal care has prompted the appearance of a new type of patient: the
      Technologically-Dependent Child (TDC), a heterogeneous and loosely-defined group
      whose survival is dependent on technological and pharmacological artifacts. A
      Government pediatric hospital in Rio de Janeiro, the Instituto Fernandes Figueira
      (IFF/FIOCRUZ) cares for this group. When eligible patients return home, they are
      enrolled in the Interdisciplinary Home Care Program (PADI) run by this
      Institution. This paper discusses the life maintenance equipment purchase and
      maintenance network, analyzing how families absorb technology so as to become
      homecare givers and take decisions. Finally, it also examines how families,
      hospitals and funding agencies must cooperate in order to care for the TDC at
      home and at this Institution. This qualitative research project is based on
      observations and interviews conducted at hospital facilities and children being
      treated in their homes through the Interdisciplinary Home Care Program.

PMID- 18813464
TI  - [Perceptions and attitudes among parents and guardians on the use of pediatric
      medicines and their cariogenic and erosive potential].
AB  - The study assesses the perceptions of parents/guardians on the use of pediatric
      medicines and their cariogenic/erosive potential, interviewing them on the
      relationship between the use of pediatric medicines and cavities/dental erosion,
      as well as oral hygiene procedures after the medication. Among the interviewed
      parents/guardians (n=86), 24 (27.9%) mentioned the sour taste of pediatric
      medication, 51 (59.3%) the bitter taste, and 56 (65.1%) considered them sweet,
      although only 16 (28.6%) of these parents/guardians brushed their children's
      teeth after the medication (Fisher's Exact; p>0.05). Moreover, only 18 (20.9%) of
      the parents/guardians performed oral hygiene practices after the medication, of
      whom 8 (44.4%) received previous instructions (Fisher's Exact; p<0.05). The
      association between taking medications and dental caries or structural dental
      defects was mentioned by 61 (70.9%) of the parents/guardians, with 24 (39.3%) of
      them justifying this association through the presence of sugar in the
      formulations. Although parents/guardians consider medicines to be sweet
      substances and relate their use to dental caries and tooth structure flaws, most
      of them do not brush their children's teeth after taking medications and are
      unable to establish a clear cause/effect relationship for this association.

PMID- 18813465
TI  - [Characterization of caregivers for children with HIV/AIDS, addressing quality of
      life, socio-economic stratification and oral health aspects].
AB  - OBJECTIVE: This study examines perceptions, and knowledge of how to promote oral
      healthcare among people caring for children with HIV/AIDS. METHODS: A
      questionnaire was completed by people caring for children with HIV/AIDS,
      encompassing the quality of life (WHOQoL-bref); the socioeconomic stratification
      (BECC); and aspects related to oral health through the perception, care and
      promotion of oral health. Internal consistency was evaluated for the WHOQoL-bref
      domains, for the BECC questions and for the oral health questions. Cluster
      analysis was performed by WHOQoL-bref domain scores. RESULTS: The alpha-Crombach
      statistics showed that the internal consistency quality progressed: 0.9101,
      0.8027, and 0.6355, respectively, for WHOQoL-bref domains, for the ECC questions,
      and for the oral health questions. The cluster analysis generated two homogenous
      groups. There were descriptive relations between the quality of life scores and
      the BECC strata and the answers given for the oral health related themes;
      difficulties were reported in accessing dental care. CONCLUSIONS: The methodology
      and tools deployed by this survey showed consistency and coherence to the
      theoretical framework, contributing to the development of better healthcare for
      HIV+ children.

PMID- 18813466
TI  - [Breast-feeding: assessment of the implementation of a program at basic
      healthcare units in Recife, Pernambuco State (2002)].
AB  - This paper analyses the implementation level of a breast-feeding incentive
      program at Government healthcare facilities in Recife, Pernambuco State, Brazil,
      through a normative assessment conducted through 84 Family Health Teams and at 42
      Health Centers in January 2002. A tool containing structured questions was used,
      related to rules and routines for promoting breast-feeding. The Family Health
      Teams performed better, with the actions implemented in 7.1% of these Teams and
      at none of the Health Centers; they were rated as 'not implemented' for 1.2% of
      the Family Health Teams and 47.6% of the Health Centers. This leads to the
      conclusion that implementation levels are not satisfactory, reflecting
      difficulties in breaking away from clinical practice and individual habits in
      order to introduce universal and all-round health promotion measures.

PMID- 18813467
TI  - Ethical and scientific issues of nanotechnology in the workplace.
AB  - In the absence of scientific clarity about the potential health effects of
      occupational exposure to nanoparticles, a need exists for guidance in decision
      making about hazards, risks, and controls. An identification of the ethical
      issues involved may be useful to decision makers, particularly employers,
      workers, investors, and health authorities. Because the goal of occupational
      safety and health is the prevention of disease in workers, the situations that
      have ethical implications that most affect workers have been identified. These
      situations include the a) identification and communication of hazards and risks
      by scientists, authorities, and employers; b) workers' acceptance of risk; c)
      selection and implementation of controls; d) establishment of medical screening
      programs; and e) investment in toxicologic and control research. The ethical
      issues involve the unbiased determination of hazards and risks, nonmaleficence
      (doing no harm), autonomy, justice, privacy, and promoting respect for persons.
      As the ethical issues are identified and explored, options for decision makers
      can be developed. Additionally, societal deliberations about workplace risks of
      nanotechnologies may be enhanced by special emphasis on small businesses and
      adoption of a global perspective.

PMID- 18813468
TI  - [Description of attempts to obtain approval for selling medications at ordinary
      Brazilian establishments after the introduction of the Real Economic
      Stabilization Plan].
AB  - Although not legal, the practice of selling medications through unlicensed
      outlets such as stores and supermarkets has long been common in Brazil.
      Introducing the Real Economic Stabilization Plan, Provisional Measure 592/94
      allowed the sale of non-prescription medications (anodynes) in such
      establishments. However, this item was suppressed when this Provisional Measure
      was enacted as Law N masculine 9,069/95. Since then, other attempts have been
      made to establish this type of trade in medications, forbidden in 2004 through a
      decision handed down by the Superior Court of Justice. Nevertheless, this
      unlawful trade in medications still continues. Due to the scarcity of
      publications on this specific issue, this paper offers an updated overview for
      druggists, pharmacists, academics and researchers, describing the events that
      took place between 1994 and 2006.

PMID- 18813469
TI  - [Characterization of elderly diabetics receiving secondary care].
AB  - The purpose of this survey is to characterize elderly diabetics by social,
      demographic and economic variables, describing their health status, functional
      capacity and use of healthcare services, related to the time when diabetes was
      diagnosed, in order to contribute to future healthcare planning actions in this
      area. The population sample was obtained through the diabetes services at three
      endocrinology units in Uberaba, Minas Gerais State in the course of a year,
      interviewing 113 elderly diabetics at home. The simple frequency distribution was
      used for the analysis, together with descriptive measurements. Associations were
      studied through chi2 (p< 0.05) test; 72.6% of the respondents were women with
      average age of 69 years (+/- 4.6). The longest times since diagnosis (51.3%) are
      between ten and twenty years. All the respondents presented other health problems
      in addition to diabetes. The main aspects of dependence identified through
      functional capacity were: trimming toenails (23.9%) and use of transportation
      (18.6%). The time since diagnosis was not an aggravating factor for dependence
      among these elderly diabetics. However, dependency during the aging process is
      present, offering a challenge to healthcare practitioners.

PMID- 18813470
TI  - [Analysis of seniors vaccination programme in Campinas, Sao Paulo State, Brazil].
AB  - This study examines the planning, operations and assessment of a Seniors
      Vaccination Program in Campinas, Sao Paulo State, from the standpoint of
      practices adopted by central, district and local authorities and intended to
      ensure influenza vaccination coverage. The case study method was used, with work
      health process benchmarks. The primary data source was semi-structured
      interviews, with institutional documents and records serving as secondary
      sources. The field of study was the municipal coordination of this Program in two
      Health Districts and one Basic Healthcare Unit. The choice of these Districts was
      based on differing vaccination coverage, while the Unit choice was guided by its
      outstanding campaign organization. At the district and local levels, the program
      was coordinated by nurses who assigned high priority to following routines and
      rules instead of pursuing the purpose of the campaign. Insufficient analysis
      capacities were identified, with poorly networked actions, incipient
      communications methods and ineffective use of information for planning purposes.
      The results underscore the importance of adopting management practices tailored
      to the purposes of healthcare efforts, ushering in responsible autonomy among
      workers and fostering ongoing reflection on these practices.

PMID- 18813471
TI  - [Academia and the social division of nursing work in the Government sector:
      sinking or surpassing?].
AB  - This paper is based on the assumption that the widening gap between manual labor
      and intellectual tasks tends to weaken the inherent potential of the labor force.
      Its purpose is to analyze current trends in the division of labor in the
      Brazilian nursing sector. This is exemplified by the findings of recent surveys
      conducted by graduate students who studied various aspects of the work processes
      involved in healthcare, education and research through a qualitative meta
      analysis. The non-appropriation of the object by the work process agents was
      common to all three studies: the graduate students plan an approach to the object
      that is altered by the advisor in compliance with research interests; reports on
      educational experiments conducted by nurses highlight the gap between planning
      and implementation of the activities, hampering full exploration of the purpose
      of educational efforts; community health agents perform tasks assigned by the
      nursing staff. Dealing with this alienation is an urgent task, through training
      and upgrading the subjects so that they have full mastery of the object, the
      purpose and the work tools, able to share their expertise and work closely
      together with a critical approach in order to transform the epidemiological
      profiles of the various social classes.

PMID- 18813472
TI  - [Communication on health and safety risk control in contemporary society: an
      interdisciplinary approach].
AB  - This paper discusses communication as a technology for risk control with health
      and safety protection and promotion, within the context of a "risk society". As a
      component of Risk Analysis, risk communication is a technology that appears in
      risk literature, with well defined objectives, principles and models. These
      aspects are described and the difficulties are stressed, taking into
      consideration the multiple rationales related to risks in the culture and the
      many different aspects of risk regulation and control in the so-called "late
      modernity". Consideration is also given to the complexity of the communications
      process, guided by theoretical and methodological discussions in the field. In
      order to understand the true value of the communications field for risk control
      with health and safety protection and promotion, this paper also offers an
      overview of communication theories that support discussions of this matter,
      proposing a critical approach to models that include the dimensions of power and
      culture in the context of a capitalist society.

PMID- 18813473
TI  - [Impact and (im)mobilization: a study of cancer prevention campaigns].
AB  - During the past few years, the Brazilian government and society have been engaged
      in planning actions designed to prevent and control several types of cancer that
      can be either prevented or treated successfully if diagnosed early. However,
      recent data on cancer mortality rates in Brazil rebut the effectiveness of these
      actions. The literature shows that psychosocial factors associated with these
      campaigns have not received sufficient attention from the authorities and
      campaign producers. This paper analyzes comments by fifteen women undergraduates
      on seven cancer prevention campaign slogans, assessing their mobilization power
      on the basis of their association with the representation of cancer as death. The
      findings suggest an important difference between the impacts of these campaigns
      and their effective power to mobilize the population to seek treatment and
      prevention. This leads to the conclusion that psychosocial elements such as the
      social representation of cancer, self-esteem, relationships between individuality
      and collectivity, gender discourse and the ideological nature of the slogans must
      be taken into account when preparing cancer prevention campaigns.

PMID- 18813477
TI  - [Social inequalities, healthcare and well-being: opportunities and obstacles on
      the horizon of transversal public policies].
AB  - The development of a distributive justice model that is responsive to new claims
      and demands in the social policy field requires in-depth examinations and
      critiques of the ways in which public policies are drawn up and implemented.
      Reconstituting and analyzing different institutional dynamics, decision contexts
      and program performances emerge as tasks that are crucial to the quest for
      alternatives ways of strengthening integration and empowerment experiences. The
      purpose of this article is to present these issues and help affirm commitments to
      transversal and convergent public actions combating poverty, social exclusion and
      unequal healthcare.

PMID- 18813481
TI  - [The Family Allowance Program: reflecting on core issues in Brazil's income
      transfer policy].
AB  - Introduced in 2003, Brazil's Family Allowance Program was intended to unite
      several Income Transfer Programs run at the Municipal, State and Federal levels
      since 1995. Designed as an expression of the development of direct monetary
      transfers to families or individuals, its key assumption is that linking income
      transfers to poor families with structural policies and programs (mainly in the
      fields of education, healthcare and jobs) could break through the vicious cycle
      of poverty in the present and halt its future replication. Linking cash transfers
      to structuring policies and programs for poor families might well underpin a
      policy combating poverty and social inequality. This paper presents a
      retrospective of these Income Transfer Programs, examining their significance and
      scope in terms of Brazil's Social Security Policies, assessing their potentials
      and constraints as tools for fostering social inclusion.

PMID- 18813482
TI  - [Conditional cash transfer programs and food and nutrition security].
AB  - This paper analyses the relationship between Conditional Cash Transfer (CCT)
      programs and Food and Nutrition Security (FNS), based on a review of the
      literature. CCT programs spur outlays on food, particularly in dynamic markets,
      as well as investments in other goods affecting the nutritional wellbeing of
      families, including demands for healthcare and education. However, the impact on
      children's nutritional status and early childhood growth is not clear, as other
      factors also affect this process, such as: the availability of public services
      (healthcare; education; sanitation) and the costs of accessing them; duration of
      the programs; transfer amounts; family sizes and intra-family rules for
      allocating resources. The program implementation process also warrants analysis,
      as this may have positive or negative effects on values, social relationships and
      practices that may deepen poverty and undermine food and nutrition security. As
      it is vital to integrate CCT programs with other projects in order to ensure
      their impact on FNS, Brazil's National Food and Nutrition Security Council plays
      a strategic role through integrated policy planning in this field.

PMID- 18813483
TI  - [Unconditional to conditional rights: counterparts in Brazil's Family Allowance
      Program].
AB  - This paper analyzes the concepts and challenges of the counterpart contributions
      demanded by Brazil's Family Allowance Program, which requires mandatory school
      attendance for children and adolescents, and healthcare for children, pregnant
      women and breast-feeding mothers. These issues are prompting much discussion in
      Brazil and elsewhere in the world. This study charts theoretical aspects that
      underpin arguments for and against conditional cash transfer programs, through a
      review and systematization of the literature and a study of the related
      legislation. This analysis demonstrates that the opponents of counterpart
      obligations claim they breach unconditional rights to citizenship. Some
      supporters of these conditional transfers believe that a return is required for
      these benefits, while others see such requirements as a strategy for ensuring
      easier access to social welfare services, thereby breaking away from the cycle of
      poverty. Although latter view is present in Brazil's original Family Allowance
      Program, the manner in which supplementary legislation defines the application of
      the conditions is coercive and remote from the concept of social insertion.

PMID- 18813484
TI  - [Social spending in Brazil: income transfer programs versus social investments].
AB  - This paper compares the dynamics of social spending in Brazil, with lower outlays
      on basic services and more direct monetary transfers through means-test programs,
      highlighting the fact that as Brazil's social safety net concentrates on cash
      transfer programs without simultaneously increasing per capita outlays on
      education, basic sanitation and housing, it is not resolving the issue of
      inequality. This paper works with secondary data from the National Household
      Sampling Survey, together with Federal, State and Municipal budgets.

PMID- 18813485
TI  - [Welfare policies on the fringe of capitalism: the recent situation in Brazil].
AB  - Located on the fringe of global capitalism, lacking an international currency and
      endowed with weak technology production and dissemination capacities, Brazil is
      developing its own very specific approach to social welfare policies. Its 1988
      Constitution ushered in acknowledged progress in these policies during the past
      two decades, despite constraints due to the general behavior of its lackluster
      economy, with rising unemployment and a shrinking job pool. In parallel, the semi
      stagnation of its per capita income has been paced by a steady stream of tax
      adjustments, hobbling more recent developments in social spending. All these
      efforts often achieve little more than upholding the wealth financialization
      cycle, mainly for the tiny portion of society holding public debt papers. An
      analysis of this specifically Brazilian situation leads to a better understanding
      of missed opportunities for cutting away many of Brazil's social shackles, as
      welfare policies have significant impacts on lower-income segments of the
      population.

PMID- 18813486
TI  - [Marketizing of the State, erosion of democracy and impoverishment of
      citizenship: global tendencies?].
AB  - This article analyses the advance of the neo-liberal regime, in order to
      contextualise the international formulation of policies focussed on poverty
      reduction. In recent debates, terms such as 'citizenship' and 'democracy' have
      been subject to critical scrutiny, revealing changes in the relations between
      citizens and the State which accompany the hegemony of economic criteria that put
      financial considerations at the centre of national states. We argue that analyses
      of such global processes require an ample political economy perspective, capable
      of illuminating how the substance of democracy and the legitimacy of state
      authority have been conditioned by the advance of new global entities that
      represent the interests of capital, favouring the concentration of wealth and the
      increase of poverty, inequality and exclusion, and installing a state of vital
      insecurity that affects the majority of the world's population.

PMID- 18813487
TI  - [Healthcare rights and conditional cash transfers in Latin America].
AB  - Conditional cash transfer programs in Latin America impose specific requirements
      and responsibilities on beneficiary households, in order to upgrade education
      levels, improve drop-out rates and eliminate child labor, while enhancing health
      and nutrition indicators. Although counterpart healthcare conditions are common
      to all these programs, government strategies differ in terms of reaching their
      goals, at times even undermining improvements in the living conditions of more
      vulnerable segments of the population. Instead of upholding rights to healthcare,
      such initiatives may well trigger a new cycle of tightly-focused basic care
      through provisional programs.

PMID- 18813488
TI  - [Implementation of Brazil's Family Allowance Program: experiences at Sao
      Francisco de Itabapoana and Duque de Caxias].
AB  - This paper discuss the findings of a study examining the Implementation of
      Brazil's Family Allowance Program in Rio de Janeiro at Sao Francisco de
      Itabapoana and Duque de Caxias, conducted in 2004 - 2005 with the support of the
      Brazilian Science and Technology Research and Development Council (CNPq) and
      collaboration among ENSP-FIOCRUZ, UFF and UERJ. Its purpose is to analyze this
      implementation process and local management practices, identifying the main
      contours of this program. An examination of its political and institutional
      dynamics, accountability mechanisms, intersectoral arenas, investments in
      healthcare and education, and intergovernmental arrangements helps outline some
      of the conflicts, tensions and challenges associated with conditional cash
      transfers as a core policy in the battle against poverty and social inequalities.

PMID- 18813489
TI  - [The right to healthcare: integrity, diversity, and territoriality].
AB  - Examining some issues and challenges for ensuring the universal right to
      healthcare in Brazil, this paper explores the findings of a government project
      conducted in 2003 to broaden the approach to healthcare problems in Brazil, based
      on dialogs between government and society that supplement institutionalized
      approaches to social participation in healthcare management. Starting with an
      overview of the complex international backdrop against which government actions
      take place for implementing social rights, this paper highlights three issues
      among the problems listed that are rated as crucial for drawing up public
      policies: integrity and dignity as pillars for the organization and regulation of
      public interventions; recognition and respect for difference as a condition for
      achieving the right to healthcare; and territorialization of problems and
      policies for the production of responses to new realities. Finally, it lists some
      aspects that challenge Brazilian government and society in their efforts to
      guarantee the right to healthcare, affirming the timeliness of the steps taken by
      the government administration, moving steadily ahead towards effective universal
      access to this right through an appreciation of aspects related to human rights
      and citizenship.

PMID- 18813490
TI  - [Transformations and continuities in Canadian social welfare programs].
AB  - Poor mothers and their families constitute a core dilemma for a social welfare
      system that aims primarily to encourage and keep workers in the labor force.
      Public income transfers to these and other marginalized groups may be viewed as
      disincentives to seek paid work and have been characterized in Canada by
      stinginess and contradictions since the beginning of the XX century. This paper
      discusses recent transformations in these programs and their effects on families
      and individuals. Focusing specifically on poor mothers raising children alone, it
      argues that many gradual cuts and reshaping these programs have changed the
      character of the social welfare state in Canada, blocking escape routes from
      poverty for marginalized groups.

PMID- 18813491
TI  - [Policy networks combating hunger and poverty: the Solidarity Community strategy
      in Brazil].
AB  - This paper analyzes a strategy deployed by the Brazilian Government for combating
      hunger and poverty: the Solidarity Community (1995-2003), particularly
      institutional mechanisms used to fine-tune targeting processes and allocate
      resources to the Food Stocks Distribution Program (PRODEA) and the Undernourished
      Child and High-Risk Pregnancy Program (PCDMI). Primary data were obtained through
      interviews with policy network players, including segments of government and
      society: nine Federal; six State and 82 from eight Municipalities in Rio de
      Janeiro state. Moving towards its goal of converging programs for the poorest
      municipalities, the Solidarity Community made them more visible to executive
      civil servants. The introduction of different sectors into the Solidarity
      Community network varied, according to the political clout and institutional
      capacity of each sector. The Solidarity Community strategy was: to negotiate
      criteria with Ministries for setting priorities and provide technical support and
      information for local governments, improving their skills for obtaining federal
      funding. The role of the Solidarity Community was thus limited at the local
      level, due to poor intersectoral networking and difficulties in monitoring
      program implementation and beneficiary selection processes, blunting its
      advantages for more vulnerable groups.

PMID- 18813492
TI  - [Poverty, malnutrition and obesity: interrelationships among the nutritional
      status of members of the same family].
AB  - Chronic malnutrition in infancy and obesity associated with short stature in
      adulthood may share common biological and socio-environmental determinants. An
      analysis of intra-family nutrition status distribution patterns may provide
      elements for understanding the risk factors common to these physiological
      conditions. The purpose of this study is to ascertain how the intra-family
      distribution of nutritional conditions in pauperized families occurs, examining
      related social, environmental and biological factors. An impoverished population
      (income less than US$ 70) was studied in two rural areas of Sao Paulo State,
      Brazil: Monteiro Lobato and Santo Antonio do Pinhal. The sample consisted of
      members of these families, with 215 children younger than 71.11 months; mothers
      (197), fathers (167) and siblings (6 to 18 years of age). A hierarchical logistic
      regression analysis model was prepared. The mothers' educational levels, the
      number of rooms in the home, age below 24 months and problems at birth, were all
      associated with height deficits in children, together with short maternal
      stature, especially when associated with obesity. Additionally, a marked
      association was noted between height deficits in these children and chronic
      malnutrition among their older siblings (6 to 18 years old). Children aged 24
      months or less presented more severe risks of delayed growth.

PMID- 18813493
TI  - [Beliefs and influences on weight loss diets among low-income obese individuals].
AB  - Obesity has become an epidemic that requires immediate control, mainly among the
      poor, particularly women and the less educated. The WHO requests and several
      studies confirm that support is needed for research projects examining
      psychological and social behavior that hampers compliance with weight loss diets.
      This paper uses the Theory of Reasoned Action (TRA) of M. Fishbein (1975) in
      social psychology, comparing two series of open interviews (conducted in 2001 and
      2005) that disclosed positive (advantageous) and negative (harmful) beliefs about
      weight loss diets among low-income obese patients in Joao Pessoa, Paraiba State,
      as well as their guides (people of influential opinion) on following their diets.
      The 2001 findings were corroborated in 2005, revealing fears of diseases related
      to obesity and the wish to feel healthier and lighter. Mothers, children and
      above all spouses were mentioned as diet supporters. It was stressed that will
      power is not be enough, but also reflection and building up control skills, in
      addition to allocating and altering life styles. Concerns related to appearance
      were not high priority. This information may lead to better diet compliance.

PMID- 18813494
TI  - [Globalization, poverty and health].
AB  - This paper analyses the relationship between globalization, poverty and health,
      defining and presenting the main characteristics of contemporary globalization.
      It also establishes the characteristics of poverty today, both globally and
      regionally. Reviewing articles and world reports, it presents a set of evidence
      on the relationships between globalization and poverty, as well as their
      influence on health. Furthermore, it presents the opportunities offered by
      globalization, through a series of worldwide initiatives prompted by actions
      among countries under the aegis of the United Nations in general and the WHO in
      particular, in addition to intergovernmental alliances and coalitions and other
      civil society representatives.

PMID- 18813495
TI  - Exposures to airborne particulate matter and adverse perinatal outcomes: a
      biologically plausible mechanistic framework for exploring potential.
AB  - This article has three objectives: to describe the biologically plausible
      mechanistic pathways by which exposure to particulate matter (PM) may lead to
      adverse perinatal outcomes of low birth weight (LBW), intrauterine growth
      retardation (IUGR), and preterm delivery (PTD); review evidence showing that
      nutrition affects biologic pathways; and explain mechanisms by which nutrition
      may modify the impact of PM exposure on perinatal outcomes. We propose an
      interdisciplinary framework that brings together maternal and infant nutrition,
      air pollution exposure assessment, and cardiopulmonary and perinatal
      epidemiology. Five possible biologic mechanisms have been put forth in the
      emerging environmental sciences literature and provide corollaries for the
      proposed framework. The literature indicates that the effects of PM on LBW, PTD,
      and IUGR may manifest through the cardiovascular mechanisms of oxidative stress,
      inflammation, coagulation, endothelial function, and hemodynamic responses. PM
      exposure studies relating mechanistic pathways to perinatal outcomes should
      consider the likelihood that biologic responses and adverse birth outcomes may be
      derived from both PM and non-PM sources. We present strategies for empirically
      testing the proposed model and developing future research efforts.

PMID- 18813496
TI  - [Healthcare practices in Nursing and Communication: a review of the literature].
AB  - Changes in nurse healthcare practices, especially for projects such as Brazil's
      Family Health Program, prompted us to study the related communication processes.
      A review of the literature from January 1994 through to December 2004 examined 26
      papers in Brazilian and international periodicals, four dissertations, three
      theses and four books in the BIREME data-bases (LILACS and SCIELO-Br). Using
      'Communication', 'Family Health Program' and 'Nursing' as key words, 373 mentions
      were found for 'Communication' and 'Nursing', twelve mentions for 'Family Health
      Program' and 'Communication' (LILACS); eighteen mentions for 'Communication' and
      'Nursing'; and no mentions for 'Family Health Program' and 'Communication'
      (SCIELO-Br). In order to analyze these findings, the publications located through
      this search were grouped under four trends in the links between Communication and
      Nursing practices: Communication within the Family Health Program teams;
      Communication in professional Nursing practice; Communication as a leadership
      tool for Nurses; and Communication in Nursing education. This study showed that
      although the most usual communication model for healthcare practices is still
      unilinear, there is already a clear trend towards more dialogue, which poses a
      challenge for nursing practices in the Family Health Program.

PMID- 18813497
TI  - [Social determinants of odontalgia in epidemiological studies: theoretical review
      and proposed conceptual model].
AB  - The epidemiological literature has been limited by the absence of a theoretical
      framework reflecting the complexity of causal mechanisms for the occurrence of
      health phenomena / disease conditions. In the field of oral epidemiology, such
      lack of theory also prevails, since dental caries the leading topic in oral
      research has been often studied through a biological and reductionist viewpoint.
      One of the most important consequences of dental caries is dental pain
      (odontalgia), which has received little attention in studies with sophisticated
      theoretical models and powerful designs to establish causal relationships. The
      purpose of this study is to review the scientific literature on the determinants
      of odontalgia and to discuss theories proposed for the explanation of the
      phenomenon. Conceptual models and emerging theories on the social determinants of
      oral health are revised, in an attempt to build up links with the bio
      psychosocial pain model, proposing a more elaborate causal model for odontalgia.
      The framework suggests causal pathways between social structure and oral health
      through material, psychosocial and behavioral pathways. Aspects of the social
      structure are highlighted in order to relate them to odontalgia, stressing their
      importance in discussions of causal relationships in oral health research.

PMID- 18813498
TI  - [The right to share in the nation's wealth: from the Family Allowance Program to
      Basic Citizenship Income].
AB  - This paper presents the positive outcomes of Brazil's Family Allowance Program,
      in terms of combating hunger and eradicating poverty, stressing that this is the
      first step towards introducing a Basic Income for Citizenship (RBC - Renda Basica
      de Cidadania) in Brazil, as established in 2004 through Law N degrees 10,835.
      This Basic Income for Citizenship will be phased in by stages at the discretion
      of the Executive Branch, starting with the neediest segments of the population.
      Everyone will be endowed with the unconditional right to receive an income that
      will be sufficient - as far as possible - to cover vital requirements. This is
      not a matter of charity or welfare, but rather an across-the-board right to share
      in the wealth of the nation. The rationality of this tool for ensuring real
      freedom and dignity for all is also examined here.

PMID- 18813499
TI  - [Depression and neuropsychological testing in patients with temporomandibular
      disorders].
AB  - A cross-sectional retrospective study was undertaken, with the primary objective
      of discovering if there were any neuropsychological differences among and within
      groups. The California Verbal Learning Test (CVLT) and the Brown-Peterson
      Consonant Trigram Auditory Memory Test (CCC) were used. Depression was assessed
      by the Beck Depression Inventory (BDI - Portuguese Version).The
      neuropsychological tests used did not present any statistically significant
      differences among the three groups studied, which might be due to the low
      proportion of patients with post high school education (20%). However, the
      experimental group (Groups I plus II) showed higher scores on depression (p<0.05)
      than Group III. In addition, Group II showed higher levels of depression (p<0.01)
      than Group I, and no statistical differences were found between Group I and III.
      Taken together, these results suggest that memory tests are highly dependent on
      the education levels of the participants and cannot be widely used. Additionally,
      depression plays a role not only in the etiology, but also in the perpetuation of
      TMD.

PMID- 18813500
TI  - [Transtheoretical model approach in eating behavior].
AB  - The study of eating behavior has been much interest, as this is an essential
      element for the success of dietary interventions. In view of the complexity of
      the subject and the countless influences to which it is subject, it is suggested
      that an in-depth exploration of eating behavior determinants enhances the impact
      of programs promoting healthy dietary practices. Increasingly more frequent, the
      adoption of inadequate diets in Brazil and elsewhere in the world leads to
      questions about the impact of dietary interventions traditionally applied to
      population groups. Many nutritional education strategies are currently described
      in the literature; however, motivating people to change their eating habits is
      still a major public health challenge. Applying the transtheoretical model seems
      to have a promising role for an enhanced understanding of changes in eating
      habits that are targeted by dietary interventions. Strategies that are tailored
      to each step in these changes, as identified by this theory, can motivate people
      more effectively to adopt healthier eating habits.

PMID- 18813501
TI  - [Private home healthcare and its strategies (apparent and hidden)].
AB  - This paper analyses the findings of an investigation into private home
      healthcare. Considered the most visible model of Managed Healthcare, it is being
      developed through the supply of multiple services. This concept is based on a set
      of principles - out-of-hospital care, lower infection risks, family-based
      benefits for patients - all linked to a cost-cutting strategy. Some labor
      relations aspects are also discussed that underpin the development of this type
      of care.

PMID- 18813502
TI  - [Impacts of non-transmissible chronic diseases on social security benefits].
AB  - This paper strives to identify the current impact of Non-Transmissible Chronic
      Diseases (NTCDs) on sickness and disability benefits paid out by Brazil's
      National Social Security Institute (INSS) between 2000 and 2002. A total of
      17,970 new cases were studied, registered at the two local agencies in Recife,
      Pernambuco State, Northeast Brazil. Initially the cases were divided up according
      by major diseases groups, following the CID-10 classification. Osteomuscular
      diseases (OMDs) and cardiovascular diseases (CVDs) were among the main reasons
      for granting sickness benefits. Among the disability benefits, CVDs, mental
      disorders (MDs), and OMDs, were the main reasons. In terms of specific diseases
      within the major DCNT groups, the main reasons for granting sickness benefits
      were high blood pressure, diabetes mellitus, arthrosis, breast and intestinal
      cancer, mood disorders and schizophrenia. For disability benefits, the main
      causes were cerebrovascular diseases, diabetes mellitus, cancer of the gastro
      intestinal tract and schizophrenia. Most (66%) of the recipients were men between
      39 and 58 years of age, and the initial value of the benefit was of up to three
      minimum wages per month.

PMID- 18813503
TI  - [Adding physiotherapy practitioners to family health teams and Brazil's National
      Health System (SUS): challenges in training].
AB  - This paper presents the role of the physiotherapist in the Family Health Program,
      particularly with regard to all-round care, analyzing the academic education of
      physiotherapists in terms of this Program from the standpoint of the players
      involved, based on an analysis of the Physiotherapy Course at the Tubarao campus
      of the Southern Santa Catarina State University (UNISUL). Similar to a case
      study, a qualitative survey was conducted, interviewing three Family Health
      Program nurses, three teachers, two interns and the Deputy Coordinator of this
      course. The data were analyzed through an examination of the contents of the
      collected responses. The closing remarks of this paper stress that the
      understanding of the nurses and the students of the role played by the
      physiotherapist in the Family Health Program is guided by diseases. This
      indicates a need for better-informed lecturers and coordination on this matter to
      avoid this repercussion, extending experiences in the Family Health Program built
      up during the course and preparing practitioners for working in teams providing
      all-round care.

PMID- 18813504
TI  - [Elderly people living in Florianopolis: self-perception of oral health
      conditions and use of dental services].
AB  - This paper is based on the Florianopolis Municipality Senior Citizen's Profile
      (2004) built up on the questionnaire in the Brazil Old Age Schedule (BOAS),
      applied to 875 elderly people. The data highlighted by this cross-section are
      related to the self-perception of the respondents of their oral health condition
      and use of dental services, which were then associated with the socio-demographic
      variables. The discrepancy between oral health data perception and actual oral
      health status - such as high percentages of missing teeth and dentures -
      discloses the way in which the elderly perceive this aspect of their own health.
      The state of their teeth was associated only with family income. Recent visits to
      dentists were associated with the need for dentures and medical referrals. This
      study indicates a need for public policies focused specifically on the oral
      health of the elderly, in addition to ways of promoting health and wellness for
      all during the irreversible aging process.

PMID- 18813505
TI  - [Influence of social class on clinical reasons for tooth loss].
AB  - In order to determine the influence of social class on clinical reasons for tooth
      loss in Maceio, the Alagoas State capital in Northeast Brazil, a cross-sectional
      study was conducted of 466 adults whose ages ranged from 18 to 76 years.
      Socioeconomic and demographic data were collected through a questionnaire.
      Clinical examinations determined the reason for extracting teeth, recording the
      DMF-T of all patients, who were divided into social classes on the basis of the
      data gathered from the questionnaire: 54.1% of the subjects were female with a
      mean age of 33.73 +/- 13.68 years; 369 (79.2%) of them had not completed their
      secondary education and 385 (82.6%) had family incomes no more than four times
      the official minimum wage (mean 3.4 +/- 5.4). The main reason for the loss of
      permanent teeth was caries. The patients presented an average of 16.59 +/- 6.96
      decayed, lost or filled teeth and most of them (219 - 47%) had a DMF-T of 11 to
      20 teeth. A statistically significant difference was noted between reasons for
      tooth loss and social class (P<0.001), leading to the conclusion that social
      class significantly influenced clinical reasons for tooth loss.

PMID- 18813506
TI  - [Professional practices in public dental healthcare: case study of two municipal
      districts, Bahia State, Brazil].
AB  - This paper examines the working facilities and processes of dentists in the
      primary healthcare systems of two towns in Bahia State, Brazil, striving to
      analyze the extent to which factors related to dental care, training, placement
      and professional profiles influence their practices. Semi-structured interviews
      were conducted with nine dentists in both towns, with work process organization
      patterns in Municipality C being closer to the structuring principles of Brazil's
      National Health System than in Municipality E. This seems to be related to
      management characteristics, with networking links among individual, collective,
      and preventive clinical activities and planning noted in Municipality C. Despite
      these differences, the practitioners presented similarities in terms of dual
      militancy and perceptions of the public and private healthcare fields. The
      hegemony of the private sector seems to be influencing the professional practices
      of dentists in the public health system.

PMID- 18813507
TI  - [Sanitary and socio-environmental conditions in the Iauarete indigenous area, Sao
      Gabriel da Cachoeira, Amazonas State, Brazil].
AB  - OBJECTIVE: To describe sanitary, social and environmental conditions that are
      significant for health of residents in the Iauarete Indigenous Area in Brazilian
      Amazonia, notable for its population concentration. METHOD: Qualitative and
      quantitative methodologies were used, with the action research method deployed
      mainly for qualitative approaches, through community meetings with tribespeople
      and researchers in the villages constituting the hub of the Area. Talking maps
      were prepared and interviews were conducted, together with studies of solid
      wastes disposal techniques, in addition to locating, sampling and analyzing the
      quality of water used for human consumption, in parallel to the use of geo
      referencing techniques. RESULTS: Of the 65 water samples analyzed, 89.2%
      presented fecal coliforms, with no adequate sanitary solutions found for the
      disposal of solid wastes. From the public health standpoint, the sanitary
      practices of these indigenous peoples caused concern, clashing with their own
      relative knowledge. CONCLUSIONS: The specific set of problems associated with the
      way of life imposed by mainstream society requires the implementation of joint
      activities in the infra-structure and health education fields in order to solve
      collective health issues, stressing local community participation.

PMID- 18813508
TI  - [How could Gerontology, a multidisciplinary field of knowledge, be included in
      CNPq's Table of Knowledge Areas?].
AB  - We discuss the possibility of including Gerontology in the CNPq Areas of
      Knowledge Table, in a scenario where this Table is being questioned by the
      scientific community, particularly with regard to the inclusion of
      multidisciplinary areas. Based on Foucault, we view the Tree of Knowledge as
      taxonomy, a continuum in which all areas are placed side by side, closer together
      or further apart, depending on their similarities and differences. This finite
      linear approach establishes that a certain Area of knowledge may be placed only
      at a point along the line corresponding to a Greater Area. Inherently
      multidisciplinary, gerontology has not been placed in this institutionalized
      taxonomy, due either to problems related to concepts, interests and political
      projects in its establishment as a field of knowledge, or because this taxonomy
      would be not be compatible with its multidisciplinary nature. We conclude that it
      is possible to draw up a new Fields of Knowledge and Expertise Table, addressing
      studies of aging - as well as all and any Fields of Knowledge and Expertise - in
      their full multidisciplinarity, together with their transformations over time.

PMID- 18813509
TI  - [Informed consent for dentistry in public hospitals, Federal District, Brazil].
AB  - Personal powers of decision and individuality must be respected, grounded on
      autonomy expressed through informed consent. This paper examines data on the
      actual use of informed consent in public hospitals in Brazil's Federal District.
      A questionnaire was completed by dentists in public hospitals, and its findings
      show that verbal informed consent is obtained at the start of treatment in most
      of the hospitals. Errors were noted in the use and conceptualization of informed
      consent. Failing to distinguish between image rights authorization and informed
      consent, the documents provide little information and do not explain important
      aspects of the treatment. Dentists practicing in the public hospital network thus
      need more detailed knowledge of basic bio-ethics in order to merge the long
      consolidated and regulated principle of welfare with the principle of autonomy.

PMID- 18813511
TI  - [Which "health promotion"? Discussing proposals for the pharmacologist's role in
      health promotion].

PMID- 18813512
TI  - [The importance of the use of stem cells for public health].
AB  - Stem cells were elected 'Breakthrough of the Year' by Science(1) magazine in
      1999, having shown that stem cells from adult tissues retained the ability to
      differentiate into other tissue types. During the previous year, the first human
      embryo stem cell lines were established. Since then, the number of scientific
      papers on stem cells has been increasing exponentially, establishing new
      paradigms that are rapidly challenged by subsequent experiments. This paper
      reviews the stem cell research field, divided into two groups: embryo and adult
      stem cells. While the differentiation potential of the former is well
      characterized in mice and humans, their use in cell therapy and research has been
      hampered by histocompatibility, safety and ethical issues. In contrast, adult
      stem cells do not present these problems. However, the extent of their plasticity
      is still under investigation. Nevertheless, numerous clinical trials in humans
      are under way, mainly with stem cells derived from bone marrow. This paper
      discusses discuss the importance of working with both classes of human stem cells
      in order to fulfill the promise of stem cell therapies.

PMID- 18813513
TI  - [Clinical trials using stem cells to treat heart diseases in Brazil].

PMID- 18813514
TI  - [Bone marrow stem cell therapies for Chagas' disease cardiopathy and chronic
      hepatopathies: from the animal model to the patient].

PMID- 18813515
TI  - [Stem cells in the treatment and cure of diabetes mellitus].

PMID- 18813517
TI  - [Brazil's Family Health Program according to healthcare practitioners, managers
      and users].
AB  - OBJECTIVE: To examine perceptions among Healthcare Practitioners, Managers and
      Users of Brazil's Family Health Program (FHP) in two municipalities in Minas
      Gerais State, Brazil. METHODOLOGY: Semi-structured interviews with the
      Practitioners and Managers focused on: professional training, Family Health
      Program goals, teams and difficulties encountered in the municipalities; Users
      responded to a structured questionnaire in households registered with four
      healthcare units in these municipalities, selected through a random draw.
      RESULTS: Practitioners reported that: the requirements for a good team include
      the personal attributes of its members; they are not satisfied with the FHP
      organization; prevention is its main goal. Managers ranked intervention at the
      family level as its main benefit, also mentioning health promotion, education and
      assistance as other important aspects. Users indicated that: community health
      agents are the most outstanding professional category; specialists are required
      in the FHP; most respondents are not engaged in any health-related activities
      other than consultations; specialized services are preferable to the FHP.
      CONCLUSION: There are different expectations among all those involved in the FHP,
      which may undermine the effectiveness of its services.

PMID- 18813518
TI  - [Evaluation of oral health actions in the Family Health Program in the Mosqueiro
      district, Para State, Brazil].
AB  - The extension of Brazil's Family Health Program Teams through the introduction of
      Oral Health Teams (OHT) as required by Decree N degrees 1,444 dated December 28,
      2000, was an important step in the restructuring of the Oral Healthcare System,
      ensuring easier access to good quality dental care and treatment for less
      privileged segments of the population. In the Mosqueiro district of Para State,
      an Oral Health Team was added to the Family Health Program in 2002, working
      closely with the local community through home calls and school visits, as well as
      at the Family Health Unit. In order to assess these Oral Health activities, 103
      users of the Family Health Program Unit responded to a questionnaire with closed
      and semi-open questions in July 2004. The resulting data were tabulated, showing
      that most of these users were young adult women with high school diplomas but
      lacking access to higher education. This public felt that Oral Health quality had
      improved considerably, being satisfied with the performance of the current team.

PMID- 18813519
TI  - [Satisfaction with dental care: qualitative study of the mothers of children
      treated at the Santa Catarina Federal University, Brazil].
AB  - This survey examines perceptions among mothers of the treatment provided through
      pediatric dentistry clinic at the Santa Catarina Federal University and their
      concept of the 'ideal' dentist, using the qualitative (case study) method.
      Collected through semi-structured interviews with seven mothers of children
      treated at this pediatric dentistry clinic, the data showed that these mothers
      felt the 'ideal' dentist should blend affective, psychomotor and cognitive
      abilities: enjoying his work; being attentive and friendly; providing clear
      information about oral health; resolving oral problems presented by patients; and
      keeping up-to-date. Interpersonal aspects were crucial factors for satisfaction
      with the treatment provided at the University, in addition to the technical
      skills of the students and easy appointments at the pediatric dentistry clinic. A
      better understanding of the relationship between dentist and patient is
      suggested, associating affective factors with cognitive and psychomotor aspects
      in dental practice routines.

PMID- 18813520
TI  - [The identity of the community healthcare agent: a phenomenological approach].
AB  - The structure of Brazil's National Health System (SUS) is being firmed up through
      programs adding a new element to its multi-professional healthcare teams:
      Community Healthcare Agents. This study examines psycho-social factors that are
      significant for the construction of this identity, from the standpoint of these
      Community Healthcare Agents, using the hermeneutic phenomenology of Paul Ricoeur
      as its reference methodology. The subjects of this survey were seven Community
      Healthcare Agents who were asked during interviews (with informed consent and
      after approval by the Research Ethics Committee) to: 'Tell me about your
      experience as Community Healthcare Agent'. The analysis of their replies
      indicated the following topics: previous experience; capacity-building for the
      job; bonding; building up expertise; gratifying experience; feelings of
      power(lessness); communications; daily work routines, personal growth; criticisms
      of the institution; user-agent experiences; and insertion into the social
      reality. The overall analysis disclosed the phenomenon through the convergence
      and divergence of the grouping of these topics, viewed from the standpoint of
      these Community Healthcare Agents and the psycho-social aspects constructing
      their identity.

PMID- 18813521
TI  - [Social representations of nurses on the integral care available to women through
      Brazil's basic healthcare network].
AB  - Brazil's Basic Healthcare Act establishes the principle of integral care in terms
      of networking between services and professional practices, to which we add a
      dimension: the configuration of public policies. Nurses were selected for this
      survey as they handle the initial contacts with women and also because we believe
      they are endowed with an across-the-board view of integral care during the
      various phases in the lives of this population. This paper examines the social
      representations of nurses on the scope of the integral care available to women
      through Brazil's Basic Healthcare Network, explored through qualitative
      interviews with ten nurses in Mato Grosso do Sul State. These data were analyzed
      through the Collective Subject Discourse (CSD) approach, based on the Theory of
      Social Representations. The findings are presented in seven Collective Subject
      Discourses that describe the main ideas identified during the interviews. This
      leads to the conclusion that nurses have a fragmented view of women's healthcare,
      still guided by physical complaints; they cannot define integral care, repeating
      the discourse of the holistic approach without understanding what this really
      means; they work on an individualized basis, feeling that this area is not
      structured to offer integral care.

PMID- 18813522
TI  - [Social representation related to care in the family health program in Natal
      Brazil].
AB  - This study examines the core and outlying representational elements of healthcare
      constructed by Family Healthcare Program teams in Natal, Brazil, using the theory
      of social representations and the central core theory. The sample consisted of
      ninety healthcare practitioners working with this Program, with data collected
      through free word association, a questionnaire and focus groups. The core
      representation consists of attention/love and comfort, disclosing different
      understandings and showing that accumulated knowledge is supported by a view that
      is close to care-giving. However, traditional values and trivial connotations are
      maintained, hindering the implementation of more effective interventions in by
      this Program. The core composition indicated that any capacity-building efforts
      that try to modify attitudes - and thus the daily practice of these practitioners
      - must assign high priority to discussions on redefining these elements of
      attention/love and comfort. They must consider the set of mental, emotional, and
      practical elaborations as well as explanations arising from daily life that are
      introduced into the constitution of the social representations under examination,
      influencing choices and shaping the strategies used by practitioners to provide
      care.

PMID- 18813523
TI  - [The fragility/strength of human life in rural communities of the Pantanal
      wetlands, Mato Grosso State, Brazil].
AB  - From an ambiguous/complex standpoint, the fragility/strength of human life
      suggests an approach based on observations of the life-style dynamics of specific
      population groups. Conducted between 2003 and 2005, this study of a community
      living alongside the Pantanal Wetlands Private Natural Heritage Reserve
      established by the Social Enterprise Support Centre (RPPN/ SESC) in the
      Joselandia Rural District, Barao de Melgaco Municipality, Mato Grosso State,
      Brazil, explores its life-style, linking explanations of the health/disease
      process to historical, economic and social aspects of this community and the
      singularity of local healing practices, using historical documentary records,
      statements from local residents, a population poll, interviews and observations.
      Changes were noted in the links of solidarity among community members at work and
      for growing food. Healing practices based on folk-medicine are alternatives used
      to relieve symptoms and diseases. The fragility/strength of this specific
      community is established through strength based on solidarity and family ties,
      while its fragility is due to difficulties in accessing work, healthcare services
      and public facilities.

PMID- 18813524
TI  - [Administration committee: analysis of the possibilities of self-management in a
      public hospital].
AB  - This paper analyzes the possibilities for self-management through an
      Administration Committee in a public hospital in Sao Paulo State, examining this
      experience and identifying the collective arrangements established from the
      standpoint of self-managed areas. This analysis focuses on the production
      dynamics of subjective aspects that pass by the Administration Committee of the
      hospital under examination, using the daily records of the institution and simple
      observation as the research methods. Charting the Committee processes indicated
      the establishment of collective activities guided by models based on shared
      management experiences, where the introduction of processes assigning joint
      responsibility can promote a management style with room for the dynamics of
      singularization. This paper also comments on some elements constituting self
      management movements that are apparent in the conflict triggered by hetero
      management processes.

PMID- 18813525
TI  - [Breast-feeding as a source of prevention in healthcare].
AB  - The importance of breast-feeding has been addressed through multi-professional
      approaches. As healthcare practitioners, dentists are included in this context
      and - due to the close links between breast-feeding and the development of the
      stomatognathic system - should be able to advise pregnant women and new mothers
      on this practice, with countless benefits for mothers and their babies. This
      paper thus presents up-to-date and enlightened information through a review of
      the literature that supports the benefits of breast-feeding, urging heightened
      awareness of its importance and the preparation of policies and actions
      implemented through Brazil's National Health System (SUS) that rank breast
      feeding as a high-priority goal.

PMID- 18813526
TI  - [Punishment, penalty or providence? Morbidity due to external causes in basic
      healthcare, Porto Alegre, Brazil].
AB  - This research project is based on the work of the External Causes Observer Group
      for Municipal Health Services under the Partenon and Lomba do Pinheiro District
      Administration in Porto Alegre, Brazil. It reflects on the actions and roles of
      Health Services in response to injuries due to External Causes, from the
      standpoint of strategies promoting health and quality of life. The high rate for
      these events prompted dissatisfaction among local healthcare parishioners, keenly
      aware that they constitute a serious Public Health problem. Coping strategies
      were initially intended to keep records of injuries due to external causes in
      this region, involving the entire team. Subsequently, the assistance rendered to
      victim of accidents and violence was examined. The findings of this group were
      presented at special events and community meetings, in addition to activities
      specifically addressing healthcare workers. Awareness-heightening and better
      qualifications are expected to underpin commitments to networking and the
      implementation of initiatives providing protection, particularly for more
      vulnerable segments.

PMID- 18813527
TI  - [Integral healthcare model for treating problems caused by alcohol and other
      drugs: perceptions of users, their companions and practitioners].
AB  - Based on an integral healthcare model for the users of alcohol and other drugs,
      the expansion of Brazil's Psycho-Social Care Centers - Alcohol and Drugs (CAPS
      AD) is guided by the acknowledgement of users as citizens rather than patients,
      aiming at social reinsertion through an intersectoral approach and damage
      control, as well as other principles designed to build up integral healthcare
      services that are fair and egalitarian. This paper examines alcohol and drug
      users, their companions and healthcare practitioners in terms of the existing
      healthcare model, through a study conducted at two Psycho-Social Care Centers -
      Alcohol and Drugs in Recife, Pernambuco State. Focus groups, participative
      observation and documentary surveys were used to analyze the daily work routines
      at these Centers, exploring player perceptions and therapeutic projects. The
      findings indicate that users are still perceived as being ill, with
      medicalization and other traces of care models not used since the Psychiatric
      Reform. Social reinsertion was perceived as the main obstacle in integral
      healthcare. Restructuring this practice seems necessary, in order to break away
      from a culture of prejudice, exclusion and illness, as well as control models
      based on hospital-centric psychiatry.

PMID- 18813528
TI  - [Vague and diffuse symptoms in biomedicine: a review of the literature].
AB  - The purpose of this study is to chart academic output on vague and diffuse
      symptoms in biomedicine. As methodological tool, we conducted a bibliographic
      study through the Internet ranging from 1990 to 2005. Forty papers were selected
      and five major theme areas were established for the survey: the nomenclatures
      assigned to vague and diffuse symptoms; their definitions; the relevance of the
      theme being addressed; the criteria used to diagnose vague and diffuse symptoms;
      and the therapeutic actions adopted. The discussion of the findings identifies
      many biomedical difficulties in dealing with sufferers from undefined complaints,
      including: diversity and lack of conceptual precision in the use of the
      nomenclature; physicians who are poorly prepared to deal with these patients;
      demand considered as a psychic disorder; difficulties in establishing diagnostic
      criteria and poor use of treatment resources. This leads to the conclusion that
      the biomedical model behind these difficulties has few tools for dealing with the
      singularities of human suffering and its experiential phenomenological dimension.

PMID- 18813529
TI  - [Prevention of prostate cancer from the viewpoint of patients with arterial
      hypertension and diabetes mellitus].
AB  - This exploratory study is designed to identify user knowledge of prostate cancer
      prevention, in a sample consisting of 100 users with arterial hypertension and/or
      diabetes mellitus being treated at a healthcare facility in Fortaleza, Ceara
      State, Brazil. Collected through interviews, the data were organized into
      categories and analyzed on the basis of user experiences and selected literature.
      Most (68%) of the users were born in rural areas, with 53 (77.9%) of them from
      the State Capital; some 53% earned one to three minimum wages; with most (52%)
      having merely started their basic education; 65% knew nothing about prostate
      cancer prevention. Among the latter, nine (13.8%) had taken the prevention
      examination and 35 had been advised about it, with twelve (34.2%) having
      undergone the preventive procedure. Failure to opt for this examination was
      related to a lack of knowledge, prejudice and the absence of symptoms. However,
      this may also be due to gaps in user healthcare education, medical practitioners
      whose attentions are focused on other problems such as hypertension and/or
      diabetes mellitus, and poor access to healthcare services.

PMID- 18813530
TI  - [Ways of inserting physicians into the healthcare production process: case of
      study of basic healthcare units in Belo Horizonte, Brazil].
AB  - The main purpose of this paper is to describe and analyze the ways of inserting
      physicians into the health production process. This subject is justified by a
      belief that that this way of working may be a problem but at the same time may
      well be the key to implementing healthcare models that are ethically and
      politically committed to the lives of public health system users. Initially, the
      problem is presented through the construction of an archetype physician and his
      historical and social and cultural conditioning factors, taking the work
      processes of physicians at Basic Healthcare Units in Belo Horizonte as an example
      that is built up through interviews and participative observations. Some
      possibilities for intervention are indicated through the introduction of new
      concepts and technologies that could transform the work of these practitioners in
      ways that would build up links with more responsibility for the care and lives of
      users of public healthcare services.

PMID- 18813531
TI  - [Representations of informal jobs and health risks among housemaids and
      construction workers].
AB  - During the past few decades, the Brazilian labor market has been characterized by
      an increase of unregistered workers, earning lower wages, not covered by social
      insurance or occupational risk prevention programs. This study describes the
      representations and perceptions about informal work contracts and job-related
      health risks, analyzed in a group of injured unregistered workers. This was a
      qualitative study based on in-depth interviews carried out with seventeen
      laborers, nine housemaids and eight construction workers. The findings indicate
      that workers recognize the importance of formal jobs, mainly because of legal
      guarantees of labor rights, mentioning the symbolic downgrading of informal jobs
      that undermines their self-esteem. Both work groups tended to minimize
      occupational health risks in the work environment, and did not recognize
      associations between informal job contracts and occupational accidents or
      diseases. It was clear that workers want to have job contracts. The findings of
      the study demonstrate the need for broader dissemination and discussion about
      labor rights and the construction of public policies that encompass health and
      safety programs for these workers.

PMID- 18813532
TI  - [Health education actions for the prevention and control of dengue fever: a study
      at Icarai, Caucaia, Ceara State, Brazil].
AB  - This study analyses education actions and their strategies for preventing and
      controlling dengue fever, highlighting constraints and difficulties. Conducted
      through a qualitative approach at the Primary Care Unit and 8 properties in
      Icarai, Ceara State, Brazil, its 17 subjects are divided into groups: I (8 PCU
      users); II (4 Endemic Disease Control Agents); and III (5 healthcare
      practitioners). The data was collected through semi-structured interviews;
      participative observation and documentary analyses, using a hermeneutic dialectic
      analysis method. The findings indicate that health education actions are
      divergent, while transforming actions are ineffective in terms of impacts on the
      disease. Difficulties include: weak location-specific actions; educational
      messages whose contents are not tailored to their contexts; authoritarian and
      coercive strategies; absence of public policies; gaps between PCU and local
      population; stress on public health campaigns; practitioners who do not listen to
      the population and vice-versa; with technical expertise still prevailing over
      users. The evidence underscores the need for actions strengthening the
      possibilities of empowering the subjects, helping them become responsible for
      their own lives and citizenship construction processes.

PMID- 18813533
TI  - [Disabled adolescents: sexuality and stigma].
AB  - This paper is designed to extend discussions of disability and sexuality,
      highlighting the expectations, beliefs, desires and experiences of young people
      with physical disability and presenting the partial findings of the doctoral
      research project entitled "You laugh because I am different, I laugh because you
      are all the same: dimensions of the quality of life in adolescents with spina
      bifida", which discusses the quality of life in two cultures: Brazilian and
      American. The perception and interest of the participants, and their need to
      discuss problems related to their sexuality and its implications for their
      families, friends and healthcare services spurred investigations of this topic in
      greater depth, indicating the need to address concepts of sexuality on broader
      bases. The discourse of these youngsters stresses four aspects related to the
      experience of sexuality: (1) Sexuality and care; (2) Sexuality, body image and
      discredited characteristics; (3) Sexuality of people with special needs from the
      standpoint of violence, and finally; (4) Sexuality and questions about medical
      information.

PMID- 18813534
TI  - [Medical rationalities and integrality].
AB  - The purpose of this article is to examine integrality as the ruling principle of
      Brazil's National Health System (SUS) from a comparative perspective, based on
      works coordinated by LUZ and cols. on the concept of "medical rationality" and
      also on Fleck's epistemology. Integrality has different meanings according to
      patients and specialized healers; it is more relevant to the latter, for whom it
      represents a permanent mission, being linked to the healer patient relationship.
      Integrality constitutes a difficult problem for biomedicine, whose expertise has
      torn the patient apart and focused its actions on "biomedical diseases". For this
      field of medicine, the more specialized the environment, the more integrality is
      blocked. The possibility of mitigating these blocks lies on the outskirts of
      specialized circles, found in the work of multidisciplinary teams, properly
      ranked by Brazil's National Health System (SUS) as the focus of Primary or Basic
      Healthcare. On the other hand, other rationalities such as homeopathy or
      traditional Chinese medicine have facilitative knowledge and practice for the
      inner circles of integrality, and the challenge - in addition to its incipient
      presence in this System - is to draw integrality away from its original esoteric
      circles into the world of its practices.

PMID- 18813535
TI  - [Euthanasia and the paradoxes of autonomy].
AB  - The principle of respect for autonomy has proved very useful for bioethical
      arguments in favor of euthanasia. However unquestionable its theoretical
      efficacy, countless aporiae can be raised when conducting a detailed analysis of
      this concept, probably checkmating it. Based on such considerations, this paper
      investigates the principle of autonomy, starting with its origins in Greek and
      Christian traditions, and then charting some of its developments in Western
      cultures through to its modern formulation, a legacy of Immanuel Kant. The main
      paradoxes of this concept are then presented in the fields of philosophy,
      biology, psychoanalysis and politics, expounding several of the theoretical
      difficulties to be faced in order to make its applicability possible within the
      scope of decisions relating to the termination of life.

PMID- 18813536
TI  - [Self-assessment in graduate public health programs: characteristics and
      constraints].
AB  - The purpose of this paper is to discuss the characteristics and constraints of
      internal appraisals or self-assessments in Graduate Public Health Programs,
      conducted through a study of the report on 25 programs participating in the three
      year CAPES evaluation (2001-2003). Three main aspects were considered: (a) tools
      and/or procedures employed; (b) self-assessment procedures; (c) products for
      upgrading program quality. The findings indicate that different tools are
      employed and used improperly. For most of the programs, it is not clear how
      ongoing processes take place, as the products presented are not directly related
      to the process as performed and the program quality assurance procedures. The
      importance of self-assessment is discussed as a tool for exploring the
      possibilities and boundaries of a process or an institution, as well as for
      taking decisions. A suggestion is presented: setting up a basic structure with
      working groups and a self-assessment coordination team; real participation and
      commitment among staff members and decision-makers; reliable data with effective
      use of the findings.

PMID- 18813537
TI  - [Prostate cancer prevention: a review of the literature].
AB  - This study analyzes recommendations for the prevention of prostate cancer
      reported in the specific literature on this topic. The method consisted of a
      review of this matter, adopting a qualitative approach, examined through the
      theme content analysis technique. Based on the following analysis categories:
      primary prevention, secondary prevention and masculinity and prevention, the
      discussion of the study findings concludes that: (a) the recommendations are
      either diverse or present some controversies among the various viewpoints; (b)
      the output of scientific papers in the collective health field is sparse on this
      matter; (c) the development of a more interdisciplinary approach is required for
      dealing with this matter and (d) few sources take the specific characteristic of
      maleness into account for recommendations on the prevention of prostate cancer.

PMID- 18813538
TI  - [The subject in academic literature on healthcare management: notes on the issue
      of autonomy].
AB  - The paper analyses concepts of the 'subject' in academic literature on Healthcare
      Management. The corpus of the survey consists of papers published in journals in
      the Collective Health field over the past five years. The papers examined for
      this analysis consider that (healthcare) work in the context of capitalism is
      based on an antinomy that we call "autonomy-control", striving to explore the
      possibilities of surmounting this antinomy in each concept. The analysis lists
      three different concepts of the subject: psychological-cognitivist,
      psychoanalytical-subjectivist and historical-communicative. This paper also
      discusses the relationship between these concepts of subject and their
      possibilities of producing autonomy on one hand, and the capitalist organization
      of culture and labor on the other.

PMID- 18813539
TI  - [Concepts involved in the training and work processes of community healthcare
      agents: a bibliographical review].
AB  - This paper is the outcome of a bibliographical review that aims at systemizing
      references in the literature to concepts involved in the training and work
      processes of community health agents under the Community Health Agent Program
      (PACS) and the Family Health Program. Published in scientific journals, manuals
      and official documents through to October 2004, 504 articles were consulted, of
      which 49 were selected and examined in full. The findings were systematically
      arranged under four themes, reviewing controversial aspects raised by authors,
      outstanding among which are: the 'discourse of change' statements in official
      documents, defining the Family Health Program as a reorientation strategy for the
      Primary Healthcare Model; the scope and ambiguity of understandings of the role
      of mediator and definitions of the duties and responsibilities of Community
      Healthcare Agents, as well as the gaps in their training.

PMID- 18813540
TI  - Environmental exposures and gene regulation in disease etiology.
AB  - Health or disease is shaped for all individuals by interactions between their
      genes and environment. Exactly how the environment changes gene expression and
      how this can lead to disease are being explored in a fruitful new approach to
      environmental health research, representative studies of which are reviewed here.
      We searched Web of Science and references of relevant publications to understand
      the diversity of gene regulatory mechanisms affected by environmental exposures
      with disease implications. Pharmaceuticals, pesticides, air pollutants,
      industrial chemicals, heavy metals, hormones, nutrition, and behavior can change
      gene expression through a broad array of gene regulatory mechanisms. Furthermore,
      chemically induced changes in gene regulation are associated with serious and
      complex human diseases, including cancer, diabetes and obesity, infertility,
      respiratory diseases, allergies, and neurodegenerative disorders such as
      Parkinson and Alzheimer diseases. The reviewed studies indicate that genetic
      predisposition for disease is best predicted in the context of environmental
      exposures. And the genetic mechanisms investigated in these studies offer new
      avenues for risk assessment research. Finally, we are likely to witness dramatic
      improvements in human health, and reductions in medical costs, if environmental
      pollution is decreased.

PMID- 18813541
TI  - [Construction of a healthcare-related information technology education praxis for
      graduate school].
AB  - This paper presents an overview of an information technology education practice
      for healthcare practitioners in graduate school. Based on hands-on experience of
      the Information Technology Applied to Healthcare classes at the Jequie Campus of
      the Southeast Bahia State University (UESB) for the Nursing and Physiotherapy
      courses, an experience is reported that stresses the importance of teaching
      information technology by establishing links between Information and
      Communications Technologies and the praxis of the healthcare practitioners,
      enhancing the educational process and allowing students to 'visualize' how such
      technologies could be used for producing and qualifying impacts on their
      professional activities.

PMID- 18813543
TI  - The need for adequate ethical guidelines for qualitative health research.
AB  - This paper discusses adequacy as to the application of Brazilian guidelines,
      Resolution 196/96(1) and complementaries to qualitative health researches,
      considering that these are based on non-positivistic paradigms. Frequently,
      decisions about the research are made together with the studied community. There
      is a concern with justice and social change. And, since subjectivity can be
      considered their privileged instrument, such researchers seek a balance between
      objectivity and subjectivity, discussing how to overcome the researcher's view.
      We have studied the application and the concept of research found in
      international and in the Brazilian guidelines. We have noticed that they adopt a
      positivist conception of research, which establishes 1) the hypothesis test, 2)
      that all procedures are previously defined by the researcher; 3) neutrality of
      the researcher and of the knowledge produced. We will present some
      characteristics of qualitative research; the ethical implications in the way as
      qualitative research is conceived in non-positivist paradigms and a brief history
      of these guidelines. Our conclusion: it is inadequate to analyze qualitative
      researches using these documents, and we suggest the design of specific
      guidelines for them.

PMID- 18813544
TI  - On ethics regimes and the problem of maintaining the face of qualitative
      research: a commentary on Iara C. Z. Guerriero's and Sueli Dallari's paper.

PMID- 18813545
TI  - A difficult dialogue.

PMID- 18813546
TI  - Rigor and ethics: challenges in qualitative research.

PMID- 18813547
TI  - Ethical guidelines and qualitative research on health.

PMID- 18813548
TI  - Methodological procedures and ethical decisions.

PMID- 18813549
TI  - Anthropological contributions for thinking and acting in the health area and its
      ethical dilemmas.
AB  - This paper attempts to analyze the way in which the issue of ethics in social
      research is dealt by institutional commissions based in biomedicine criteria.
      This discussion is particularly important for Social Sciences in Health, as our
      projects must necessarily be presented to Committees for assessment. In actual
      fact, Resolution N masculine 196/1996 issued by the National Health Council
      establishes this mandatory requirement for all social areas. However, there is a
      question among researchers working with social issues, arguing that the health
      sector is moving outside its field when attempting to regulate actions in other
      fields of investigation. Grounded on philosophical anthropology, this paper is
      divided into three parts: (1) elements of anthropological foundations of ethics;
      (2) contributions of Anthropology to thinking about ethics and human rights in
      health; (3) internal and external questioning about anthropological practice. I
      conclude that if the ethical issue that involves human beings cannot be reduced
      to the procedures established by Ethics Committees, discussions in greater depth
      are required among social scientists on the construction of a practice based on
      and guided by respect for the intersubjectivity of all the players engaged in a
      research project.

PMID- 18813550
TI  - Research and the (free and) informed consent.
AB  - The aim of this article was to reflect about the Free and Informed Consent (IC)
      in qualitative researches in the health field. Coming from the experience of
      being part of a CER (Committee for Ethic in Research) in the health area the
      authoresses place in debate some important questions, exploring them and
      conducting suggestions. One of these questions and topic of analysis is the
      meaning of IC, as for the participant as for the researcher.

PMID- 18813551
TI  - Ethical aspects considered by researchers who use qualitative approaches in
      health.
AB  - The paper first analyzes the ethical question of qualitative researches from the
      philosophical viewpoint, and the bioethical question as an interdisciplinary gap
      that enlarges from the seventies. Afterwards, the question on qualitative
      research considered as technique and art is raised and understood in a
      philosophical way of thinking science as a theoretical body, which is
      epistemically organized in the face of the social reality investigation, and as a
      movement instituted to defend and discuss the properties of these methodologies.
      Anthropology is used as an example, and some parts of the codes of professional
      ethics of anthropology, sociology and psychology are presented. Finally,
      particularities of the social science fields are discussed, as well as the need
      to develop a code of ethics for qualitative research. In addition, ethical ways
      to work in social researches are suggested.

PMID- 18813552
TI  - [Is the principlist model still satisfactory for the analysis of the morality of
      the scientific research involving human beings?].
AB  - This paper discusses the application of principlism to research involving human
      subjects, starting from the question of its pertinence in the current situation
      of the paradigmatic pluralization on science and the multiplication of models of
      ethical evaluation in the complex societies. Highlights that the development of
      modern scientific medicine depended strongly on human experimentation and that up
      to the mid 20th century the good intention of the researcher was, theoretically,
      enough to justify a research morally, but that with the twofold paradigmatic
      transition in Science and in Ethics, occurred in the course of the 20th century,
      a pluralization and complexification took form in both the scientific know-how
      and the field of ethics applied to scientific research, which on normative level
      was in the uncomfortable situation of having to deal with a permanent
      contestation of scientific and ethic paradigms. In the field of ethics, other
      principles also pass to guide decisions such as the principles of protection,
      applicable to situations of need as they arise mainly in the case of the
      populations of the Third World. Finally, principlism is pertinent in its general
      philosophic posture and methodological value, but insufficient when applied to
      the moral problems of public health and in particular to research ethics in
      dependent countries.

PMID- 18813553
TI  - Re-imagining the "subject:" conceptual and ethical considerations on the
      participant in qualitative research.
AB  - The conventional biomedical concept of the "human subject" is out of step with
      World Health Organization's (WHO) holistic definition of health. The "human
      subject" in international and national research-ethics policies is a highly
      individualistic, autonomous person, in contrast to WHO's holistic definition of
      the healthy person. Qualitative research, this paper suggests, offers a way out
      of this conundrum. We need to reconceptualize the human "subject" in line with
      WHO's holistic definition of health. The paper offers concepts of "research
      participants" derived from qualitative research as an essential way to
      reconceptualize the human "subject." Moreover, field work, or ethnographic
      research, as undertaken by qualitative researchers presents a useful way of
      gaining a fuller understanding of issues of health in a given population.

PMID- 18813554
TI  - Beyond the informed consent procedure: continuing consent in human research.
AB  - An ethnographic field study about informed consent in hepatitis C clinical trials
      provides insight into how changes in protocol requirements and patient health
      status triggered the actions and decisions of researchers and human subjects
      during the conduct of these trials. U.S. federal guidelines recommend that
      informed consent should be conceptualized as more than a one-time event. Rather,
      a process of continuing consent should be the standard but little is understood
      about how exactly this process should unfold. We used a proposed typology of
      continuing consent to frame our analysis and were able to document that only some
      of the proposed types took place at the site of our study. The most frequent
      practice involved the researchers' re-consent of their subjects for major
      protocol revisions. Only one subject dissented and chose to withdraw even though
      he was technically eligible to continue in the study. Two other types of
      continuing consent were not observed. We discovered an additional type of
      continuing consent not described in the typology whereby subjects gave implied
      consent through their cooperation and adherence to the on-going requirements of
      the protocols. Implications for the informed consent process and the need for
      further research are presented.

PMID- 18813555
TI  - [Participative research and health researcher's ethical formation].
AB  - The present article discusses Ethics concept as dwell and way of dwelling, aiming
      to articulate it with some elements of participative research from an
      ethnographic matrix. Mainly, it focuses the idea of the ethical subject's
      autonomy, associating it with self-reflection and alterity in ethnography. Yet,
      it approaches the participative research in an ethnographic perspective as a
      praxis that induces to health researcher's ethical formation.

PMID- 18813556
TI  - Ethics in research with human beings: some issues about psychology.
AB  - This paper examines some ethical issues in research with human beings, especially
      addressing the area of Psychology, such as the use of ethical codes; minimum
      risk; informed consent; debriefing; confidentiality; and ethical committees. It
      suggests ways for researchers to increase understanding and the proper use of the
      ethical codes, to guarantee their own protection, and to avoid abuses of power.
      Special attention is given to methodological issues related to ethics.

PMID- 18813557
TI  - [Henri Atlan's levels of ethics and the challenge of the "fourth level"].
AB  - This article presents the ideas on ethics by the contemporary French biophysicist
      and Spinozist philosopher Henri Atlan, based on his singular epistemological
      position, in constant transit between naturalistic philosophy (in alliance with
      cognitive sciences) and his refusal to a natural foundations of ethics. It
      underlines Atlan's defense of casuistry towards bioethics dilemmas and associates
      it to his proposal of different levels of ethics. The text introduces a
      reflection concerning Atlan's ideas about the possible passage between the third
      and the fourth levels of ethics, stressing its positive impact in individuals and
      social groups' life quality.

PMID- 18813558
TI  - [Research ethics in social sciences--new challenges].
AB  - This paper aims to discuss how already established principles of research ethics
      can be incorporated to the ethical review of research projects in Social
      Sciences, particularly ethnographic studies or studies using the techniques of
      participant observation and open interviews. The discussion is guided by an
      analysis of the methodological and ethical procedures used in the production of
      the ethnographic documentary "Severina's Story". The analysis of the film shows
      the urgent need to expand the horizons of the debate around research ethics
      beyond the biomedical fundaments of this field.

PMID- 18813559
TI  - [A systematic review about the scientific production with focus on the relation
      between health and environment].
AB  - The discussion on points linked to the interface between the environment and
      health has turned into a very important subject of interest nowadays. Thus, this
      article aims to show a survey of the national and international scientific
      production about this subject, in an attempt to identify the most frequent themes
      of this production. The data were collected during the months of March and April
      of 2005, from two homepages where scientific publications are available on the
      web, from which, 603 publications were used as analysis material, by means of
      categorization. The data showed that there is a very significant number of
      countries with scientific production on this area, being the most frequent the
      USA and Russia, whose most relevant theme area is related to risk evaluation.
      Brazil appears as the third most frequent country in terms of production and most
      of its work is directed to the study of vectors (transmitters) of infecting
      contagious diseases. About the other countries, there is a diversification of
      lines of investigation. In general, it is perceived that the production of
      knowledge of this area still occurs in a very isolated and fragmented way, with
      little importance to the diversity of factors involved in the environmental
      questions, as well as with little space to interdisciplinary and inter sectorial
      work, so important in the analysis of the interface health-environment.

PMID- 18813560
TI  - Reviewing the environmental and human health knowledge base of carbon nanotubes.
AB  - Carbon nanotubes (CNTs) are one of the most promising materials in
      nanotechnology. The various synthesis, purification and postprocessing methods
      produce CNTs with diverse physical characteristics, appliable in many fields.
      Their extensive projected use makes it important to understand their potential
      harmful effects. Besides showing a notable range of results of some toxicology
      studies, this review concluded that: a) there are different types of CNTs; thus,
      they cannot be considered a uniform group of substances; and b) in environmental
      compartments, CNTs can be bioavailable to organisms. Their properties suggest a
      possible accumulation along the food chain and high persistence. In organisms,
      CNT absorption, distribution, metabolism, excretion and toxicity depend on the
      inherent physical and chemical characteristics (e.g., functionalization, coating,
      length and agglomeration state), influenced by external environmental conditions
      during CNT production, use, and disposal. Thus, characterized exposure scenarios
      could be useful in toxicology studies. However, upon reaching the lungs in enough
      quantity, CNTs produce a toxic response (time and dose-dependent). The risks to
      human health and environment should be identified for a successful introduction
      of CNTs in future applications.

PMID- 18813561
TI  - Ethics in epidemiological research.
AB  - This text focus, on a series of author's opinions, on the difficulties that the
      current system of regulation of ethics in research represents for the practice of
      the epidemiological research, in the Country. It introduces a few understandings
      concerning the present subject in the international literature, pointing out some
      of the most relevant themes and problems. It also examines part of the
      difficulties faced by Brazilian epidemiologists. The main topic developed in the
      article is the specificity of the science's reasoning that guides acting of the
      public health and epidemiology with repercussions for the practice of scientific
      research in this field, plenty different from the science's reasoning that
      preside medical practice and biomedical research. Hence the inadequacy of the
      ethical recommendations in force, all of them based on biomedical research,
      particularly at that with experimental design. It concludes with the indication
      that procedures adopted by the system of the ethics in research should be
      reviewed, adapting such procedures to the characteristics of different kinds of
      research.

PMID- 18813562
TI  - [Synthesis of the reflections of the meeting on ethics in qualitative health
      research, Guaruja, Sao Paulo State].
AB  - This article presents a synthesis of the report collectively elaborated in the
      meeting on Ethics in Qualitative Health Research, which took place in Guaruja,
      Sao Paulo State, from August 28 to 30, in 2006. The meeting was organized by the
      Ethical Committee of the Municipal Health Office of Sao Paulo, supported by the
      Special Programme for Research and Training in Tropical Diseases (TDR), sponsored
      by UNICEF/UNDP/World Bank/WHO and stressed the need to review the Brazilian
      guidelines for the analysis of the ethical aspects of qualitative health
      research.

PMID- 18813563
TI  - [Bodies and pleasures in male homosocial circuits of downtown Rio de Janeiro].
AB  - This paper presents the results of an ethnographic research investigating the
      cultural bases that guide the construction of corporeal events, especially those
      related to sex/eroticism, in the homosocial circuits of downtown Rio de Janeiro.
      Data were gathered by means of biographic narrative interviews, direct
      observations and research-interventions. The main argument presented in this
      paper is that the diverse corporeal events in the studied community are based on
      the same conceptual structure that focuses on transgression of the "body/flesh"
      in the sense of St. Paul's concept: an exaltation of forbidden 'tesao', erotic
      pleasure only admissible for the purpose of reproduction. 'Flesh' instead of
      sublimated being exalted, constantly inspired and attracted to more and more
      erotic pleasure.

PMID- 18813564
TI  - [Hypertension in impoverished social segments in the state of Sao Paulo].
AB  - The objective of the current study was investigating the relation between socio
      economic, environmental and biological factors and hypertension according to
      gender, taking into consideration peculiar forms of work, leisure and life-style.
      The target population consisted of 677 adults of impoverished social segments of
      two cities in the State of Sao Paulo, Brazil, 274 (39.8%) men and 415 (60.2%)
      women. The study was conducted by applying a hierarchical logistic regression
      model to men and women separately. The adjusted Odds Ratio (ORaj), with a
      confidence interval of 95% and a = 0.05, were calculated. The risk of
      hypertension in men increases as a result of: living in a rural area (ORaj= 2.00;
      p= 0.01), alcohol use (ORaj= 1.90; p=0.03) and being over 40 years of age
      (ORaj=2.35; p=0.003). On the other hand, large families, i.e. families with more
      than six members, exercise a protective effect (ORaj= 0.45; p=0.02). Risk factors
      associated with hypertension in women were: lack of schooling (ORaj= 2.37;
      p=0.003); sedentary lifestyle (ORaj=1.71; p=0.04); obesity associated with low
      stature (ORaj=3.23; p=0.001) and age over 40 years (ORaj=5.29; 0.0001). Obesity
      alone was not associated with hypertension (stage II or greater) in this
      population.

PMID- 18813565
TI  - [Breastfeeding protection, promotion and support at an university hospital].
AB  - A quantitative and descriptive study hold in a University Hospital in Sao Paulo
      State aimed at evaluating breastfeeding protection, promotion and support by
      ensuring compliance with the "Baby-Friendly Hospital's ten steps" for successful
      breastfeeding proposed by the Ministry of Health. The evaluation has found
      practices to facilitate breastfeeding, but some changes in the hospital routines
      in order to meet the "ten steps" must be made. On average, 79% of the answers
      were positive for the compliance with the "ten steps", which is close to the 80%
      suggested. However, if we analyze each step, we can identify items which need to
      be improved. The practice of placing the baby with the mother just after birth
      allowing breastfeeding at the first half hour, was reported by 100% and 80% of
      the interviewed mothers who had natural vaginal delivery and cesarean section,
      respectively. Investments and changes toward the compliance with the "ten steps"
      will improve the population assistance and education of baby-friendly
      professionals.

PMID- 18813566
TI  - [Ayurveda diet and the nursing consultation: a care proposal].
AB  - The present text is based on the final paper on a subject from the graduate
      program of the Federal University of Santa Catarina. In this paper, I propose the
      implementation of nursing consultations providing ayurvedic dietary advice as
      part of the services offered in Primary Care Units for assisting patients with
      diabetes mellitus and high blood pressure. For a better understanding, I bring a
      brief revision on both ayurveda medicine and diet, emphasizing the importance of
      balance and harmony of the doshas for maintaining or reaching a good quality of
      living. I believe that through the ayurveda diet we nurses can contribute to the
      health of our patients offering something we all need, a correct diet according
      to our nutritional biotype. Another positive result that can be anticipated from
      practicing this philosophical and methodological proposal lies in the
      relationship we establish with other persons, in knowing the characteristics of
      their doshas, because it is this knowledge that enables us to aid people in their
      conquests and defeats.

PMID- 18813567
TI  - [Prevalence of musculoskeletal symptoms and associated factors among metal
      industry workers in Canoas--RS].
AB  - Workers health is a field of community health that has opened spaces for
      identifying and preventing work-related diseases, especially musculoskeletal
      disorders in view of their extent and magnitude. We conducted thus a cross
      sectional study in the biggest metal industry in the city of Canoas--RS, aimed at
      identifying the musculoskeletal symptoms of a group of metal industry workers and
      the association of these symptoms with socio-demographic and occupational
      variables. Two questionnaires were employed for gathering data: the first one was
      used to collect information on demographic and occupational variables and
      individual life habits and the second for identifying the prevalence of
      musculoskeletal symptoms (Nordic Musculoskeletal Questionnaire). Results showed
      that 75.2 % of the workers had related some kind of musculoskeletal symptom
      during the last 12 months, 53.3% during the last 7 days and 38.5% had already
      taken a time off due to this problem. There was also an association between the
      musculoskeletal symptom and the variables sex, age, occupation and educational
      level. We conclude that there is a high prevalence of work-related
      musculoskeletal disorders among workers, calling for preventive actions and
      health promotion in the work environment.

PMID- 18813568
TI  - [Supraspinatus tendon affection and sick leave].
AB  - Rotator cuff disease, among others damage of the supraspinatus tendon mainly
      caused by work overload, is a common problem in the population resulting in a
      high incidence of sick leaves. In the present survey we sought to compare the
      need for sick leaves in relation to different stages of supraspinatus tendon
      affection and in relation to five different groups of workers. Our study counted
      with the participation of patients who were diagnosed with this condition. The
      individuals were grouped according to stages of the disease (tendonitis, partial
      rupture, total rupture) and according to the biomechanical aspects of their
      occupation (general services, civil construction, domestic workers, farm workers
      and security guard services). Statistical analysis was performed using Pearson's
      chi-square test, dependence analysis and exact test. Results revealed that 62
      (55%) of the individuals were on sick leave. The highest rates of sick leaves
      according to Pearson's test occurred in the groups general services (38.71%) and
      farm workers (22.58%). According to the dependence analysis, tendonitis (p<0.05)
      was the most frequent reason for sick leaves and, according to Pearson's test,
      farm work seems to keep the individual for a longer space of time unfit for duty
      (p=0.02).

PMID- 18813569
TI  - [The Family Health Program (FHP) and human resources: perceptions of students
      from two different dentistry schools].
AB  - The purpose of this study was to evaluate the perceptions and opinions of dental
      students from two different Dentistry Schools in Brazil, both known here as
      Dentistry Schools 1 and 2 about the Family Health Program--FHP. The study
      analyzed if the Dentistry Schools had any influence on the students, graduating
      professionals with humanitarian and social sensibility, which are considered very
      important prerequisites for those who wish to work on this governmental health
      program, as well as searching for professional expectation of the students.
      Individual questionnaires were applied by only one researcher among the students
      who took part in the study. Answers were analysed by the Epi-Info program and
      results showed that difficulties related to the job market may be influencing
      students to join the FHP. Results also reveal that students consider technician
      an important prerequisite for dentists who wish to work on this governmental
      program. Significant statistical differences between the students were found:
      those who were graduating in Dentistry School 1 seemed more adequate to FHP and
      the reason for this difference may be the Supervised Training Program, a unit
      available on this Dentistry School that enables the students face the reality of
      FHP, as well the social and economical reality of the families assisted by this
      program.

PMID- 18813570
TI  - [Occupational risk due to use of mercury in dentistry: a bibliographic review].
AB  - The aim of this study is to present data concerning hazardous waste management in
      the health area, with emphasis to the utilization of mercury in dentistry. The
      study was based on a bibliographic review regarding the use of mercury in dental
      fillings and its potential toxicological risks for patients and due to
      occupational exposure. The studies also take into consideration national and
      international recommendations on the use of mercury and its occupational exposure
      limits. The review of the literature reveals the potential toxic effects of
      mercury both on the environment and on human health. Given that the use of dental
      amalgam is still very frequent in dentistry, there is a need for safety
      regulations in order to minimize the risks posed by dental amalgam in dentistry
      proceedings based on technical guidelines for its use, discard and final
      disposal.

PMID- 18813573
TI  - [History, health and its workers: from the international agenda to the Brazilian
      policies].
AB  - This article discusses the agenda for the training and management of the health
      workforce in Brazil from a historical viewpoint, especially as refers to its
      relations with the programs in this field developed by the Pan American Health
      Organization (PAHO) and by the World Health Organization (WHO). In the first
      section one discusses the role of history in the field of community health. The
      priority given to the topic health work in the international agenda seems to
      point to a potential renewal of the relations between history and health. The
      second section provides a historical examination of the human resources programs
      of the WHO. In the third section, a similar examination is conducted with respect
      to the actions of PAHO in the same field. The fourth part of the article
      discusses--on the basis of the experience called "Program for Strategic
      Preparation of Health Personnel--PPREPS"--the relations between the national and
      international policies for the development of human resources in health. Moreover
      it describes a number of adapted responses and original solutions for facing the
      health workforce problem proposed by the Brazilian technicians. Finally, some
      questions are raised for discussion regarding the articulation between history
      and health workforce policies.

PMID- 18813574
TI  - [The opportunities of the history of health].

PMID- 18813575
TI  - [History, health and health workers: the international context and the
      construction of the Brazilian agenda].

PMID- 18813576
TI  - [History, public health and technical cooperation: old nexuses and new challenges
      of the globalized world].

PMID- 18813578
TI  - Divorce between theory and practice: the system of public health training in the
      United States.
AB  - Many analysts have complained about the severe disconnect between public health
      as it is taught in schools of public health and public health as it is practiced
      in health departments. At least in the United States, few faculty members
      teaching in schools of public health have ever worked in public health
      departments. By the same token, few of those working in public health departments
      have degrees from schools of public health; most receive on-the-job training.
      This history traces the roots of this disconnect or "divorce between theory and
      practice." It finds that the 1930s were the prime years of community-based public
      health education, when the pressure of the Depression and the funding newly made
      available from the federal government by New Deal legislation encouraged
      practical training programs linked to local communities and health departments.
      The "divorce" began in the post-war period as an unintended consequence of the
      system for funding medical education and research at a time of general
      unpopularity of public health during the McCarthy era. Schools of public health
      were generally ignored in the 1950s and they began to adapt the strategy that
      continues today, of using research grants, primarily from the National Institutes
      of Health, to grow their faculty and facilities.

PMID- 18813579
TI  - [Male and female doctors in Sao Paulo and the Records of the Professional
      Practice Audit Service (1892-1932)].
AB  - This article aims at analyzing the profile (place of origin, nationality and
      sex), the place/institution of graduation and the insertion of physicians into
      the labor market of Sao Paulo between 1892 and 1932, a period covered by only a
      small number of studies on this topic. The source of information used in this
      survey is the collection of records of the Professional Practice Audit Service of
      the State of Sao Paulo, preserved in the Center for the Memory of Public Health.
      The present paper refers to a preliminary study, part of a broader project aimed
      at constructing a data bank and analyzing the formation and the profile of
      workers acting in Sao Paulo in different health areas, between 1892 and 1978.

PMID- 18813580
TI  - [The Brazilian Association of Workers' Medicine: a space for the constitution of
      occupational health as a medical specialty in Brazil in the 1940s].
AB  - This article analyzes the Brazilian Association of Workers' Medicine, created in
      the end of 1944 as a space for consolidating occupational health as a medical
      specialty in Brazil. The Association was founded by the first group of
      specialists in the field of occupational hygiene and medicine with seat at the
      facilities of the proper Ministry of Work, Industry and Commerce, where the
      founders were working. Counting on an initial core group of 35 physicians and
      five engineers, all of them coming from the Ministry, the main objective of the
      Association was to study, discuss and promote the issues related to workers'
      medicine. Among the most relevant activities promoted by the Association were the
      monthly scientific meetings (with lectures held by invited physicians and
      physicians and engineers of the Ministry itself), the organization of scientific
      events and the publication of a specialized periodical. In 1945, only one year
      after its foundation, the Association passed to make part of the International
      Bureau of Safety at Work, with seat in Montreal, Canada, and the International
      Bureau of Work of the International Labor Organization. In December 1945, on
      occasion of the election of the new board of directors, the Association created
      the Journal of Workers' Medicine, whose first issue was published in 1946.

PMID- 18813581
TI  - [International cooperation in health: the Special Service of Public Health and
      its nursing program].
AB  - This paper analyzes the role of the Servico Especial de Saude Publica (Special
      Service of Public Health) in developing and expanding higher education in nursing
      and to train auxiliary health personnel in Brazil under bilateral agreements
      between the US and Brazil during the 1940s and 1950s. The Nursing Program of the
      Special Service is approached from the perspective of its participation in a
      broader international cooperation developed by the Pan American Health
      Organization, but also as part of the state and nation building effort of the
      first Vargas Regime.

PMID- 18813582
TI  - [Come on my child, let's have some massage?"Puxacao", midwives and reproduction
      in Melgaco, Para].
AB  - This article presents ethnographic data, collected between 2004 and 2005, about
      the obstetric service offered by a group of 21 midwives in the city of Melgaco,
      state of Para, Brazil. The literature has largely described the work of midwives
      in Brazil and in many other countries around the world. However, there is a kind
      of practice, which was analyzed very scarcely up to now. The objective of this
      article is to discuss precisely the practice called puxacao, an abdominal massage
      performed mainly on pregnant women to alleviate indispositions, inform the
      position and sex of the fetus, help define the date and place of delivery,
      socialize women for maternity and put pregnancy into the context of the local
      patterns of reproduction, family, well being and health. It can be observed that
      these midwives offer a very suitable and appropriate pre-natal service, well
      adapted to the specific needs of the women of the town. Even though homebirth has
      been slowly giving way to hospital birth, this personalized service and practice
      keeps increasing.

PMID- 18813583
TI  - [Scientific information, medical education and health policies: the Pan-American
      Health Organization and the creation of the Regional Library of Medicine-
      Bireme].
AB  - This article examines the creation and the first years of functioning of the
      Regional Library of Medicine (Biblioteca Regional de Medicina--Bireme--PAHO),
      today Latin-American Center for Information in Health Sciences, during 1963-1982.
      In the course of this analysis, Bireme is being characterized as both an
      apparatus and an arena for negotiation present in the most general processes of
      development expressed in international cooperation, information in science and
      technology, health policies and in the movement for expansion and reform of
      medical teaching. The narrative has as initial landmark the conception of a
      regional library of medicine for Latin America according to a model proposed by
      the National Library of Medicine. The article qualifies the first years of
      Bireme's existence as the history of the reception of this model, a trajectory
      that reflected the criticism of that time against the way the health care
      services were organized and their human resources were educated. Finally,
      beginning in 1976, a new model resulted in a real modification of Bireme's
      programmatic agenda, implying in very distinct contributions for the functioning
      of the regime of information in health sciences in force in Brazil and Latin
      America.

PMID- 18813584
TI  - [Cecilia Donnangelo: a pioneer in the theoretical construction of social thinking
      in health].
AB  - The present article analyzes aspects of the intellectual trajectory of Maria
      Cecilia Ferro Donnangelo and her principal works. The text emphasizes the
      innovating and pioneer role her work played in the first moments of social
      sciences in the field of health in the mid sixties, occurring just together with
      changes in medical education and medical practice in Brazil.

PMID- 18813585
TI  - [Institutions and conflicts in tuberculosis teaching in Cordoba, 1920-1955].
AB  - The purpose of this paper is to analyze the process of institutionalizing
      tuberculosis research and teaching in the Faculty of Medical Sciences of the
      State University of Cordoba. The province of Cordoba, especially the capital and
      the northwestern region, was considered an area suitable for climatic cure. This
      caused an important flow of migration of infected people and at the same time an
      increasing interest of the argentine physicians in studying this disease. The
      analysis of the different actors that participated in the creation process of
      teaching institutions in this area will be studied with basis on Bourdieu's
      concept of 'field'. From this perspective, this paper approaches the stages of
      the disease, the development of teaching institutions, and the tensions and
      disagreements that were involved in their constitution.

PMID- 18813586
TI  - [The technical cooperation Paho-Brazil in the education of health workers (1973
      1983)].
AB  - This paper discusses the human resources policies in health in Brazil, from the
      basis of the technical cooperation in this area between the Pan-American Health
      Organization (PAHO/WHO) and the Brazilian government. The study examines the
      formulation and implementation of the "Agreement for Human Resources Development
      for Health in Brazil", especially from the beginning of the Program for Strategic
      Development of Health Personnel in 1975. The paper finally discusses the
      implications of this Program, whose reflections are felt up to the present days,
      for the institutionalization of RH in health as part of the public health
      administration, for the organization of the field of collective health in Brazil,
      and for the criticisms and reforms in the country's health systems.

PMID- 18813587
TI  - [Poliomyelitis, philanthropy and physiotherapy: the birth of the career of
      physiotherapist in Rio de Janeiro in the 1950s].
AB  - The polio epidemics in the country and especially in Rio de Janeiro left hundreds
      of children with sequels in the 1950s. The public outcry over the polio epidemic,
      the reports in the press and the association of experienced physicians with
      businessmen, bankers and relatives of victims created the conditions for the
      emergence of a philanthropic entity to combat infantile paralysis. The Brazilian
      Beneficent Association of Rehabilitation (BBAR) was founded in 1954, and two
      years later the association created the School of Rehabilitation of Rio de
      Janeiro (SRRJ), the first institution to graduate physiotherapists in the
      country. This article presents a socio-historical analysis of the establishment
      of physiotherapy as a profession in Rio de Janeiro in the course of the creation
      and accreditation of the School of Rehabilitation. It is concluded that the polio
      epidemics played a central role in the creation of the School of Rehabilitation
      and that conversely this institution had a strong influence in the recognition of
      physiotherapy as a health profession in the country.

PMID- 18813588
TI  - Multifaceted contributions: health workers and smallpox eradication in India.
AB  - Smallpox eradication in South Asia was a result of the efforts of many grades of
      health-workers. Working from within the confines of international organisations
      and government structures, the role of the field officials, who were of various
      nationalities and also drawn from the cities and rural enclaves of the countries
      in these regions, was crucial to the development and deployment of policies.
      However, the role of these personnel is often downplayed in official histories
      and academic histories, which highlight instead the roles played by a handful of
      senior officials within the World Health Organization and the federal governments
      in the sub-continent. This article attempts to provide a more rounded assessment
      of the complex situation in the field. In this regard, an effort is made to
      underline the great usefulness of the operational flexibility displayed by field
      officers, wherein lessons learnt in the field were made an integral part of
      deploying local campaigns; careful engagement with the communities being
      targeted, as well as the employment of short term workers from amongst them, was
      an important feature of this work.

PMID- 18813589
TI  - [Interrupting routes, hygienizing people: sanitary techniques and human beings in
      the actions of sanitary guards and educators].
AB  - The main interest of this article lies in understanding the connections between
      managing sanitation technologies and managing people by means of so-called health
      education interventions towards the same purpose and aim. It analyzes the
      training of two categories of professionals who were of crucial importance for
      the actions of the Special Service of Health (1942-1960) and whose existence as
      such seems to express the indissoluble link between the concepts technique and
      human being: sanitation guards and sanitation educators. By investigating the
      instruction manuals and course programs, this study aims at grasping the values
      and ideas about the health/disease process and the relationship between the human
      being and the environment valid at that time, as well as at understanding the
      functions of the sanitation guards and educators.

PMID- 18813590
TI  - [Itinerant physicians, the art of healing and doctors in national history (Mexico
      City, 1877-1911)].
AB  - The uncertainty and mistrust towards the presence and activities of academic
      medical practitioners in Mexico City during the Porfirio Diaz government (1877
      1911) convinced these professionals that is was essential to create, strengthen
      and transmit a respectable, competent and homogeneous image of the profession. To
      this purpose they recovered, recreated and adapted the ethical maxims of the
      occidental medical culture to their professional work, and rescued eminent
      medical figures of Mexico's convulse nineteenth century from being lost in the
      oblivion of history. Their goal - as it will be expounded in the following pages 
      was to respond, oppose and neutralize the criticism and disbelief expressed by
      the public against their professional performance.

PMID- 18813591
TI  - [Francisca Praguer Froes: medicine, gender and power in the trajectories of a
      Bahian woman doctor (1872-1931)].
AB  - Increasing urbanization, the growth of industry and commerce, and the beginning
      of a more favorable attitude towards women's work in the late 19th century in
      Brazil set the stage for the admission of women to higher education. Within this
      scenario, Francisca Praguer Froes graduated in the Bahian School of Medicine and
      Pharmacy, in 1893. Besides dedicating her work to Gynecology and Obstetrics, she
      has fought throughout her life for the political and civil rights of the women,
      particularly in the field of health. Noteworthy, among others, is the diligence
      with which she defends the right to health for women infected by sexually
      transmitted diseases invoking precepts of hygiene for sustaining her proposition
      from a medical standpoint. Beyond woman's health, Francisca has been active in
      the political and scientific discussions on sexual moral, as a matter of fact an
      issue barely talked about in catholic Bahia. Involved in a broader discussion
      around the construction of the bourgeoise society, she went even further
      advocating that the topics hygiene, health and sexual moral should make part of
      the general social agenda of that time.

PMID- 18813592
TI  - [Health surveillance in the Brazilian health policies and the constructions of
      the identity of the health workers (1976-1999)].
AB  - In this article, we analyze the structure of health surveillance in the country
      between 1976--when the National Secretariat of Health Surveillance was created-
      and 1999--the year of the implementation of an independently administered,
      financially autonomous regulatory agency linked to the Ministry of Health, the
      National Health Surveillance Agency. The study focuses mainly on how the field of
      health surveillance fits into the health policies, and on the changes in its
      conception passing from the connotation of "inspection" to "surveillance". The
      recognition of the importance of health surveillance in the broader field of
      Community Health as well as the specificity of its professionals are central
      points of reflection. Recent studies on this topic are beginning to reveal a
      complex field of knowledge and practices, almost invisible in health policies and
      rarely addressed amidst the new topics of Community Health, thus opening new
      perspectives for this area.

PMID- 18813593
TI  - Source of funding and results of studies of health effects of mobile phone use:
      systematic review of experimental studies.

PMID- 18813594
TI  - Quantum bioethics: ethics for all beings.
AB  - The present paper introduces elements for conceiving ethics for all beings based
      on the idea of laic compassion.

PMID- 18813595
TI  - [Rate of dental treatment needs: the case of the Xakriaba Indians].
AB  - The present study was developed among Xakriabas Indians in Minas Gerais and aimed
      at identifying their needs for dental treatment so that patients could be
      scheduled for treatment. Native health agents were trained by dental-surgeons for
      conducting the survey in household visits. The total Indian population is of
      6.498 inhabitants, 3.686 of these living within the territory of the "Base Mata
      Fome", where 61% of the population was examined. Results showed that the
      population is mainly young, a great number of individuals presented no need for
      treatment and dental caries was the most frequent problem. The survey is expected
      to help in the organization of a schedule that allows giving priority to the more
      serious cases and promoting equity.

PMID- 18813596
TI  - [Profile of clinical research subjects in an independent outpatient center].
AB  - This paper assesses the quality of assistance in a clinical trial outpatient
      center as well as the patients understanding of the informed consent (IC);
      determine the reasons why they participate and detail socio-economic levels. A
      cross-sectional study was adopted in a clinical trial outpatient center using a
      self-explanatory questionnaire. All 100 respondents considered the assistance at
      the center excellent (86%) or good (9%). Almost all of them were well informed
      about the content of the IC. Their knowledge about the right to
      "confidentiality", present in all ICs, was 6 times higher than their knowledge
      about their right to "access the results", generally not included in the IC. The
      main reasons for participating were "to know more about ones health" (59%) and to
      "to benefit other people in the future" (47%). The participants income varied
      from 3 to 5 minimum wages (48%) and most (66%) concluded at least the 4th grade
      of basic education in Brazil. The subjects showed the economical characteristics
      of the average population of Rio de Janeiro. Their level of education allowed
      them to sign and to understand what they were signing. They were aware of the
      existence of the IC and its content. The main reason for participating was for
      one s own benefit and for the benefit of others.

PMID- 18813597
TI  - [High prevalence of users who did not return to the Testing and Counseling Center
      (TCC) for knowing their serological status: Rio Grande, RS, Brazil].
AB  - The Testing and Counseling Centers are important sources of epidemiological
      information. This study describes a research conducted with the users of the
      Testing and Counseling Center of Rio Grande-RS submitted to anti-HIV test during
      the period 2001-2004. Demographic and behavioral factors of individuals attended
      in the service were analyzed using the database SISCTA-2002/RG. HIV-1
      seropositivity between 2001 and 2004 was of 1,1%; 2,4%; 2,3% and 1,7%,
      respectively. In 2003 and 2004, 37,7% and 36% of the HIV-1 positive patients did
      not return to the Testing and Counseling Center for getting the result of their
      serological anti-HIV or confirmatory tests. These results seem to reflect some
      tendencies of the HIV epidemic in Rio Grande and in Brazil. It is important to
      emphasize the high percentage of HIV-1 positive patients who do not return for
      getting the result of their test. In terms of public health this risk behavior
      may jeopardize the efforts for controlling the epidemic.

PMID- 18813598
TI  - [Accessibility of legal benefits available in Rio de Janeiro for physically
      handicapped people].
AB  - According to PAHO, only 2 % of Latin America's 85 million disabled people receive
      adequate medical care. Ten percent of the world's population lives with
      disabilities without having access to their constitutional rights. Disability
      must be addressed on several levels: medical, rehabilitative, social and
      political. Disability is strongly linked to poverty. Stigma, discrimination and
      inability to pay limit access to health services and education and ill-health
      increases the treatment cost, creating a vicious circle that must be broken.
      Although the Constitution grants rights to disabled persons including access to
      health and education, these legal benefits are not always obtained or respected.
      To better understand and address the problem, the process for obtaining three of
      these legal benefits was studied among disabled pediatric patients with
      myelomeningocele in a specialized Institute in Rio de Janeiro. Results show a low
      achievement rate. Bureaucracy and the expenses with locomotion were main
      constrains worsened by lack of time and resources in families struggling with
      poverty. Other difficulties were lack of professional attention and confidence in
      the system, problems related to documents, unqualified educational system and
      locomotion constrains.

PMID- 18813599
TI  - [Evaluation of the hygienic-sanitary conditions of kitchens in public and
      philanthropic daycare centers].
AB  - This paper aims to evaluate the hygienic-sanitary conditions of kitchens in
      philanthropic and public daycare centers in the city of Sao Paulo using a tool of
      easy application. Information on the hygienic-sanitary conditions was gathered
      observing the operational conditions of five public and philanthropic daycare
      centers in the city of Sao Paulo. A score was developed for classifying the risks
      of food contamination. The operational conditions in the kitchens of the studied
      philanthropic and public daycare centers in the city of Sao Paulo can result in
      contamination of the prepared food. Among the most important risk factors for
      food contamination is the behavior of the workers who handle the food. Training
      and continuous supervision of the involved personnel are the best and easiest
      alternatives for assuring the appropriate hygienic-sanitary conditions and
      quality of the food offered to the children in these daycare centers.

PMID- 18813600
TI  - [Health and work ability of workers of the electricity sector in Sao Paulo].
AB  - The high risks for the health and work ability of the workers of the electricity
      sector notwithstanding, there is a lack of studies on this topic in Brazil. Our
      purpose is to identify the health and work ability profile of the workers of a
      private electricity company in Sao Paulo. A cross-sectional study analyzing 475
      workers of a private electricity company was adopted and data were collected
      using structured questionnaires for measuring work ability, health status, work
      stress, physical activity, tobacco and alcohol dependence. The internal
      consistency of the questionnaires was evaluated using Cronbach's alpha. The
      descriptive analysis was conducted using means, standard deviations, minimum and
      maximum values (continuous variables) and proportions (categorical variables).
      The health of the workers was found in good conditions, showing means ranging
      between 72.7 a 91.2 (in a score of 0.0 to 100.0 points). Work ability scored high
      as well, with a mean value of 41.8 (in a score of 7.0 to 49.0 points). The
      workers presented good health and work ability. Longitudinal studies should be
      conducted for evaluating causal relationships and the existence of the healthy
      worker effect.

PMID- 18813601
TI  - [The beliefs of pregnant women about dental care during gestation].
AB  - The objective of this study was identifying beliefs of pregnant women, both users
      of the Unified Health System (the Brazilian Healthcare System) and women assisted
      by the private sector, with respect to oral health and dental care during their
      pregnancy. The approach used in this survey was theme-based qualitative content
      analysis. The subjects' comprehension of the objectives of this study was checked
      in semi-structured interviews, a total of 20. Analysis and interpretation of the
      collected data revealed the existence of myths, fears and restrictions with
      regard to prenatal dental care. According to our findings the users of the
      Unified Health System seem to have dental visits on a more systematic and regular
      basis than the users of the private health sector, probably because the dental
      services offered by the prenatal program of the Primary Care Units is providing
      them with an opportunity to solve pre-existing dental problems. On the other
      hand, the users of the private health system seem to avoid scheduling dental
      visits during pregnancy.

PMID- 18813602
TI  - [The etiology of caries: the construction of a thought-style].
AB  - This study deals with the construction of the Odontological Thought Style about
      the etiology of caries. As a reference we use the theory of Ludwik Fleck (1896 
      1961) maintaining that knowledge is a result of social activity and that each
      individual with certain knowledge belongs to a certain cultural environment, a
      thought-collective sharing the same thought-style. The sources used for studying
      the transformations in the theory were classic literature and a universe of 161
      articles published between 1980 and 2001, selected from the Medline/Pubmed base
      using the key words dental caries/etiology/theoretical. Based on the analysis of
      these articles and books we identified a macro style of thinking characterized as
      multicausal-biologicist transforming the etiological knowledge mainly since the
      mid 90s. In this stage, in which the period of classicism of the theory does not
      respond any more to the reality of the disease revealed in epidemiological
      studies, five distinct trends could be identified: the biological; the clinical
      biological; the clinical-epidemiological; the biopsychosocial and the social.
      Thus, one of the challenges posed to odontology today is to transform its thought
      style adapting it to the new social reality of the disease.

PMID- 18813605
TI  - [The world is ageing: a pact of social solidarity is an imperative].
AB  - Abstract This text presents the key topics, which guided the discussions about
      demographic change and the resultant public health implications. With the ageing
      of the societies, the health problems of the elderly put pressure on health and
      social security systems. With regard to work and social wellbeing, there are
      three important sub-topics: the labor market and the elderly; social security and
      questions related to shelter for the aged population. The ageing process normally
      occurs in good health conditions unless there is disease. In addition, the
      scientific and technological achievements in the health area allow for a better
      quality of life for the elderly. This is why preventive strategies over the
      lifespan turned more important for meeting today's challenges and increasingly
      those of tomorrow. As refers to innovation and markets, longevity creates
      numberless opportunities especially in terms of new products and markets. On the
      other hand, the term "productive ageing" has been widely used for defining the
      increasing trend towards a life style in an ageing society. Finally we will
      approach the topic ageing and development showing that the demographic shift is
      already one of the most urgent global problems, being addressed by public
      policies both in the developed and developing countries.

PMID- 18813606
TI  - [The demographic window, economic growth and the public health and social
      security policies].

PMID- 18813607
TI  - [Social solidarity, a necessary utopia].

PMID- 18813608
TI  - [The world is ageing: create a pact of social solidarity is an imperative].

PMID- 18813610
TI  - [Elderly care in the supplementary health system].
AB  - The purpose of this study was to identify and analyze the assistance provided to
      the elderly by the supplementary health care system. Information was collected
      from interviews with managers of chronic diseases management programs and/or of
      specific programs in this area. Information was organized in cases and analyzed.
      Eleven companies operating private health plans in the cities of Rio de Janeiro
      and Sao Paulo were investigated. A general care model for the elderly was defined
      for the analysis. This model consists in a proposal for a care and assistance
      system hierarchically organized according to the deterioration of the functional
      capacity of the elderly (levels of dependence). None of the six companies that
      had health plans for the elderly already implemented provided full assistance to
      all enrolled seniors. There are major differences in the stage of development of
      their programs. Four companies had already implemented plans and two companies
      had plans in development. Even with the teams of managers and professionals
      working on some level within the advocated model, none of these companies
      followed any logic of integrated care and monitoring in all stages of the ageing
      process in accordance with the degree of dependence of the associate.

PMID- 18813611
TI  - [Oral health for the elderly: an interdisciplinary approach].
AB  - The aging of the Brazilian population and the resulting change in its age
      structure require from public policies and health professionals distinct
      attitudes with regard to health care delivery, focused on interdisciplinary work.
      This text aims at emphasizing the importance of using the problematization method
      in the context of an interdisciplinary approach, in which the actions shared by
      the different fields of knowledge converge to an interactive process towards an
      integrated view of the individual.

PMID- 18813612
TI  - [Time use in the daily life of aged women: an indicative method of the life style
      of population groups].
AB  - Time use research analyzes the multi-factorial aspects of aging. The purpose of
      this research was to describe time use within a group of 75 elderly women, 68,04
      +/- 8,36 years old, based on their daily activities from waking up to going to
      sleep. The instruments used in the study were a cognition test (Clock Completion
      Test), a questionnaire for obtaining personal data and structured interviews
      (Time Diary) for obtaining information about the activities carried out on the
      day prior to the interview. The daily activities were decoded and classified by
      means of an international classification for time use studies, thus obtaining the
      profiles of the daily activities assigned to nine groups of main activities and
      their physical and social contexts. It was verified that the greater part of time
      was spent with mandatory activities (housework and personal care). Most of the
      free time was spent with passive leisure (TV watching) and little physical
      activity. Most of the activities were performed at home (physical context), and
      the elderly women used to live either with members of their family or alone
      (social context). Individual factors such as age, gender, educational level,
      marital status and socioeconomic level probably play a role in the time use
      patterns found.

PMID- 18813613
TI  - [Training professionals for delivering ingreated health care to the aged: the
      interdisciplinary experience of NAI - UNATI/UERJ].
AB  - The training of professionals in the field of healthcare for the aged is one of
      the priorities of the national policy for the aged in Brazil due to the
      accelerated aging of the population. The Nucleo de Atencao ao Idoso (NAI), a unit
      of the Open University of the Third Age/UERJ (UNATI/UERJ) develops an educational
      program in this field, based on practical care delivery with emphasis to inter
      disciplinarity and teamwork. The program includes different training levels and
      modalities: Residency, Specialization, Professional Practice and Graduation. The
      program includes an introductory course in gerontology and geriatrics common to
      all areas, and specific theoretical-practical qualification coordinated by the
      professional staff from the respective areas. The practical activities occur in
      different sceneries: long term care institutions, health promotion educational
      settings, outpatient facilities and the university hospital. Interdisciplinary
      thinking and acting is a continuous exercise, and the team should be open to
      innovative strategies. The experience is a contribution to the increasing social
      demand for qualified professionals committed with the principles of the Unified
      Health System and integrated health care.

PMID- 18813614
TI  - [The net for protection to the elderly of Rio de Janeiro: a right to be
      conquered].
AB  - This article is based on previous studies using triangulation of methods for
      investigating if violence is obstructing the rights of the elderly. A
      questionnaire with open and closed questions was applied to a convenience sample
      of 72 elderly (60 or more years of age) of both sexes. Twenty-two key-informants
      (elderly people, community leaders and representatives of public institutions)
      were interviewed. In this survey we investigate the net for protection to the
      elderly of the city of Rio de Janeiro (institutions, assistance flow,
      integration, denunciations and measures taken). We analyzed 763 records of
      occurrences of the Police Department for the Aged and 135 of the NEAPI (Nucleus
      for Special Assistance for the Aged), taken care of in 2004. We emphasize
      domestic violence committed by close relatives and point to the need of
      structuring the formal net through increasing the number of institutions for
      protection to the aged, professional qualification, communication and integration
      among the agencies composing the net. We also consider important stimulating the
      informal nets for support and protection to the elderly.

PMID- 18813615
TI  - [A population of elderly and their satisfaction with their oral health].
AB  - This mixed method study aimed at evaluating the satisfaction of elderly with
      their oral health, observing associated variables, and analyzing what would be
      necessary for satisfying their expectations with respect to oral health. Data
      were gathered by means of household interviews with 261 elderly people (city of
      Ribeirao Preto), representing the whole population of elderly registered in a
      Family Health Unit. A semi-structured questionnaire was elaborated to obtain
      information on the variables sex, age, educational level, financial independence,
      number of teeth and denture wearing. Data analysis was based on associations and
      content analysis. 49,2% of the totally toothless were satisfied whereas most of
      those who were not satisfied (73.9%) were young-elderly people (60-69). There was
      a statistically significant association between educational level and
      satisfaction (p=0,009); 76,0% of the elderly with low educational level were
      dissatisfied with their own oral health. The dissatisfied elderly related
      different situations that would make them feel satisfied. The most representative
      complaint mentioned in the interviews referred to discomfort caused by the
      denture. It was concluded that most of the elderly were satisfied with their oral
      health however, the higher the age and lower the educational level, the lower was
      the number of dissatisfied elderly.

PMID- 18813616
TI  - [Profile of the family caregiver caring for patients with sequels of cerebral
      vascular accident].
AB  - This descriptive study using a qualitative approach aimed to identify who are the
      family caregivers and to understand how the caregiver is chosen amongst the
      family members of stroke patients. Data were collected by means of a semi
      structured questionnaire applied to ten family caregivers. In addition, these
      caregivers were observed during the interview.The interviews were recorded,
      transcribed and analyzed. Most of the caregivers who participated in this study
      were females, married, partners and daughters, with a mean age of 54 years. The
      statements demonstrated that the "choice" of taking care is not so much an option
      but closely related to a feeling of obligation. Besides, this choice is also
      related to the affective relation established with the patient before the
      illness.

PMID- 18813617
TI  - [The perception of health professionals of two definitions of frailty in elderly
      people].
AB  - The objective of this study was to understand the perception of health
      professionals of two definitions of frailty in elderly people. The sample
      consisted of twelve health professionals, who work in a Geriatrics Ambulatory.
      The tools used for data collection were individual semi-structured interviews,
      and the questionnaire Definitions of Frailty, developed for that purpose. Data
      were organized and analyzed using the Collective Subject Discourse method, which
      consists of key-expressions, central-ideas and collective subject discourse. The
      results indicated that the health professionals have got difficulties to accept a
      one-dimensional definition of frailty, which is in accordance with the
      international literature. The six Central Ideas (CI) that emerged from the
      discourses were: 1) the definitions are complementary; 2) there is no potential
      for prevention; 3) defining frailty is a complex task; 4) what is the concept of
      frailty? 5) the multidimensional definition is complete; 6) frailty is a state
      that can last for life. The participants believe that these definitions
      complement each other, since frailty encompasses an interaction of biological,
      psychological, and social factors throughout the lifespan. Only one professional
      accepted the multidimensional definition as complete. Defining frailty is a
      rather complex task.

PMID- 18813618
TI  - [The secret of longevity in the perception of the old-aged].
AB  - Many studies point to factors capable of increasing longevity but many questions
      regarding this subject were still not elucidated. The perceptions of the old aged
      themselves with respect to factors that contribute to longevity are important,
      allowing to identify each factor and its interactions with other variables
      promoting longevity. This article presents the results of an investigation about
      "the secret of longevity", according to old-aged themselves, analyzed through
      grounded theory. Thirty old-aged men, former railroad workers, were interviewed
      in the city of Botucatu (SP). The analysis of their discourse led to the
      conclusion that the perception of the factors can be grouped around progressively
      inclusive categories that culminate in the collective representation that
      longevity depends on the balance between negative life-destroying factors and
      healthy, life-generating and life-preserving factors. The lack of social and
      state control over these factors is generating a pessimistic view for the future.

PMID- 18813619
TI  - [The concept and measurement of functional disability in the elderly population:
      a literature review].
AB  - This article aims to review the main concepts and measures of functional
      disability currently used in studies focusing on this subject. According to this
      review, functional disability can be defined as a difficulty or the need for help
      for performing basic or more complex daily activities necessary for keeping an
      independent life in the community. As refers to measurement criteria, the studies
      do not follow a clear-cut standard, varying substantially in relation to scales,
      dimensions and classifications besides depending directly or indirectly on the
      kind of available information. A correct method for rating functional disability
      does not exist at yet. For this reason it is essential that the researchers
      clearly indicate the concept of functional disability used in the studies and
      detail, which measures or tools were applied.

PMID- 18813620
TI  - [Study of intrinsic risk factors for falls in institutionalized elderly people].
AB  - The objective of this research was to identify intrinsic risk factors that
      predispose elderly people living in long-term institutions in the city of Goiania
      (GO) to falls. The present descriptive transversal study was carried out in six
      long-term institutions for seniors in the city of Goiania. The investigated
      sample consisted of 95 elderly that fitted the inclusion and exclusion criteria.
      A questionnaire was used for collecting clinical data related to health-disease
      conditions; cognitive data; capacity to develop basic daily life activities and
      equilibrium and gait. In general terms, as pointed out the literature, the
      examined elderly presented different fall risk factors such as: motor difficulty
      in lower limbs (90%), visual deficit (81,1%), use of 3 or more kinds of medicines
      (59,7%), suspected depression (37,9%), lack of equilibrium/unstable unipodal
      support (37,9%) abnormally decreased height in step (32,6%). The obtained data
      allow us to set indicators for the increase in falls among the studied sample,
      demonstrating the need for creating strategies for health promotion, prevention
      of injuries and rehabilitation.

PMID- 18813621
TI  - [Analysis of the self-medication pattern among Brazilian elderly women].
AB  - The elderly consume more medications than other age groups, being susceptible to
      irrational use of therapeutic drugs. This work describes a cross-sectional study
      that evaluated self-medication practiced by elderly women, who were assisted at
      the Elderly Care Facility of the hospital of the Catholic University of Brasilia.
      The socio-economical variables analyzed were age group, educational level and
      monthly family income. The pharmaceuticals were evaluated according to
      prevalence, suitability for the age group and possible drug interactions. Among
      the 218 patients interviewed, 26% declared self-medication practices, part of
      them (40%) were prescription drugs. Anti-inflammatory, analgesic and antipyretic
      drugs were the most frequently consumed without professional orientation,
      followed by phytotherapeutic/natural and cardiovascular agents. Among the self
      medicated patients 65% had incomplete or no formal basic education whereas 32%
      had earnings equal to or inferior to one minimum wage. The mean consumption of
      drugs by self-medication was not influenced by socio-economical variables. The
      practice of self-medication involves potentially harmful drug interactions and
      use of agents inappropriate for the age group.

PMID- 18813622
TI  - [Contributions toward appropriate assistance for elderly users of automatic
      teller machines].
AB  - This study focuses on some aspects related to the usability and accessibility of
      automated teller machines (ATM), identified as problematic for elderly users.
      Some of these problems can interfere with the health and the health status of
      these users. This study was carried out in two ATMs installed in agencies of two
      public bank institutions. The interaction of the users with the ATMs was
      evaluated by quantitative analysis, using a sample of 70 aged customers. The
      results demonstrated that the elderly felt uneasy using the ATMs, suffering great
      psychic pressure. This study not only rejects some of the negative
      characteristics observed in these environments but also alerts to their
      unfavorable impacts upon the health of the elderly. Moreover, it points to the
      need for improving these services and for investigations evaluating the impact of
      the psychic pressure upon the health of elderly people.

PMID- 18813623
TI  - [Nutritional evaluation and prevalence of not transmissible chronic disease in
      elderly participating in an assistance program].
AB  - The purpose of this study was to evaluate the nutritional state and the
      prevalence of not transmissible chronic disease in elderly, who were
      participating in an assistance program of the Federal University of Alfenas
      (UNIFAL-MG), Alfenas, Minas Gerais, Brazil. Socio-economical, anthropometric and
      biochemical variables, as well as systemic blood pressure were collected from 82
      individuals between 60 and 87 years of age, 90,2 % of them female. According to
      the body mass index (BMI) 52,4% of the studied sample were overweight, 28,0%
      eutrophic and 19,5% underweight; 37,8% presented high body fat percentage (BF%).
      With regard to the relation BMI/BF%, 63,4% of the elderly with overweight, 12,5%
      of the eutrophic and 11,8% of the underweight presented high BF%. The waist-to
      hip ratio revealed 40,2% at high risk and 12,2% at very high risk of developing
      cardiovascular disease. In addition, 22,0% had high blood pressure. The
      biochemical tests revealed that 39,3%, 39,3% and 3,3% presented higher plasma
      cholesterol, triglyceride and glucose levels respectively. There is a need for
      continuous nutritional education programs and monitoring of the nutritional and
      health status for improving the quality of life of the studied individuals.

PMID- 18813624
TI  - [The meaning of medical intervention and religious faith for the elderly cancer
      patient].
AB  - This study aimed at identifying the meaning medical intervention and religious
      faith have for the elderly patient with cancer. A descriptive and qualitative
      investigation was developed between January 9 and March 28, 2001 in the Hospital
      do Servidor Publico Estadual--Francisco Morato de Oliveira/IAMSPE (Hospital for
      State Public Servants). The studied sample was not randomized and consisted of 20
      elderly men and women with cancer. The data were collected in semi-structured
      interviews and organized and analyzed using the Collective Subject Discourse
      method, applying three methodological illustrations: the Central Idea, Key
      Expressions and the Collective Subject Discourse (CSD). The main central ideas of
      the discourse material were: 1. Nothing to complain about. I think it is very
      good and they are on the right track; 2. No. For now, I'm doing everything the
      doctors say; 3. I've already participated, but not currently; 4. I don't
      participate in religious activity; 5. Invigoration, hope and balance. Religious
      faith is everything! 6. It remains the same; however, it changed the way to be.
      The CSD shows that the adopted medical intervention gave the elderly renewed hope
      and that religious faith is a key instrument for facing the disease.

PMID- 18813625
TI  - [Socio-demographic differentials in the functional decline among the elderly in
      Brazil].
AB  - There is a positive reversion in the expectations regarding the health condition
      of the elderly population, possibly due to the progresses in medical technology;
      behavioural changes; development of special programmes for the elderly;
      improvements in the socio-economic status; decrease of infectious diseases. This
      study aims analyzing differentials in the prevalence rates of mobility disability
      among elderly people in Brazil. The data used were from 'The 1998 and 2003
      National Household Survey (PNAD)', conducted by the Brazilian Institute of
      Geographic and Statistics (IBGE). The two samples were nationally representative,
      including approximately 30 thousand individuals aged 60 years or more
      respectively. "Difficulty to walk more than 100 meters" was the variable selected
      as the indicator of disability. Socio-demographic status measures were sex, age
      group, region of residence and family income per capita. Comparison of the PNAD
      results of 1998 and 2003 showed that over that period in Brazil the elderly
      disability rates decreased among all socio-demographic groups considered. Public
      policies directed to the elderly must focus on reducing mobility disability.

PMID- 18813626
TI  - [The influence of falls on the quality of life of the aged].
AB  - The objective of this study is to analyze the effect of falls and their
      consequences on the quality of life of elderly people living in a low-income
      community in the city of Rio de Janeiro. This article is part of an explorative
      research conducted at CLAVES, using quantitative and qualitative methods. In this
      study we used quantitative data about falls and quality of life. 72 elderly aged
      over 60 years participated in the study. 51,4% of them were females, 20,8% lived
      alone and 37,5% admitted having suffered a fall during the last year. Among the
      most frequently mentioned consequences were fractures (24,3%), the fear of
      falling (88,5%), abandonment of activities (26,9%), change of habits (23,1%) and
      immobilization (19%). The analysis showed that falls have influence upon in the
      quality of life of the aged. The WHOQOL-Bref domain scores showed a reduction in
      the means of the group that had suffered falls during the last year in comparison
      to those who didn't fall, and the difference was more significant in the
      psychological field. In short, falls are frequent among the elderly and bring
      consequences that change the quality of life of these people in a negative way.
      Their incidence can be avoided by identifying the causes and developing
      appropriate preventive measures.

PMID- 18813627
TI  - [Representations of aging for community health agents and nursing professionals:
      psychological aspects of the health-disease process].
AB  - This paper addresses the aging process in the context of public health, with
      emphasis to human resources and to how aging is perceived by the public health
      professionals. The aim of this study was to identify the representations of the
      aging process for public health professionals and how these representations are
      expressed in health care, well-being and elderly care. The sample included 27
      public health professionals, 10 community health agents and 17 nursing
      professionals. Two instruments were used, a sociocultural questionnaire and a
      questionnaire about aging representations. Data analysis included qualitative and
      quantitative procedures (Chi-square test). Among the main findings, the most
      representative words used in relation to aging were retirement and rest. For this
      sample, good family support and care were considered the most important factors
      contributing to the well-being of the elderly. When it comes to defining care,
      the most frequent concept referred to biological aspects. Moreover, this sample
      in general showed some knowledge about Alzheimer Disease. These findings can
      contribute to the capacitation of human resources. Health agents and nursing
      professionals should be guided towards construction of a deeper comprehension of
      the biopsychosocial context of the aging process.

PMID- 18813628
TI  - [Profile of caregivers of elderly in long-term care institutions in Belo
      Horizonte--MG].
AB  - The purpose of this cross-sectional study was to determine the profile of
      caregivers of elderly in long-term care facilities. The studied population
      included 181 randomly selected caregivers, 98 from philanthropic and 83 from
      private institutions in the city of Belo Horizonte. Data were collected applying
      structured questionnaires. The variables evaluated were sex, age group,
      educational level, marital status, income, economic condition, time of work in
      the facility, and professional experience. The data were compared using Chi
      square and Fisher's exact tests. There was no statistically significant
      difference between caregivers from the two facilities with regard to sex (p=0.62)
      and income (0.77). In the philanthropic facilities we observed more caregivers
      aged 50 years or more, widowers, with less than 4 years of study, socio-economic
      level D and who were working as caregivers in the facility for more than two
      years (p<0,05). The results of this study are relevant for discussing developing
      and implementing public policies aimed at qualifying the caregivers in long-term
      care institutions for elderly in Belo Horizonte.

PMID- 18813629
TI  - [Identification of the area of influence of the public basic health care delivery
      to the elderly population in Vicosa-MG].
AB  - This study aimed to describe the demographic and epidemiological characteristics
      of the elderly population, identify the area of influence of basic care in
      relation to the area of residence of the elderly and the rate of service use, as
      well as to map the demand according to the geographic location of the Basic Care
      Unit. The sample comprised 6,964 male and female subjects aged 60 years or more,
      who sought any of the outpatient public health services between May 2003 and
      April 2004. From this total, 64.1% were women and 35.9% men. The results show
      that cardiovascular diseases account for the greater part of medical
      consultations in the health system, with a mean of 3,576 consultations per year
      per elderly. Geographic mapping showed the demand for medical consultations in
      determinate basic care units to be related with the medical specialty available
      at these units. These results allow identifying the neighborhoods with the
      highest concentrations of specific diseases, indicating the need for
      insertion/redistribution of professionals between the basic care units in order
      to improve the quality of life of the elderly.

PMID- 18813630
TI  - [The health status of the elderly population: what do we need to know?].
AB  - The objective of this research was to evaluate the data on the health of the
      elderly population available in the Brazilian information system and their
      correspondence with the North American statistics using the Internet. The North
      American publication "Older Americans 2000: Key Indicators of Well-Being" was
      used as a standard. The databases and instruments used in the North American and
      Brazilian surveys are presented. The North American data are based on the
      Supplement on Aging and Second Supplement on Aging; Health and Retirement Study;
      National Health Interview Survey and National Long Term Care Survey. The
      Brazilian data were collected from the Mortality Information System; Information
      System of the National Program of Immunizations; National Household Sample Survey
      conducted in 1998 and 2003 and from the Household Survey on Risk Behavior and
      Morbidity from Not Transmissible Diseases of 2002-2003. There is a great number
      of Brazilian information about the aged population of the Country available in
      the Internet and with few exceptions the information on aged Brazilians
      corresponds to the information available about aged North Americans.

PMID- 18813631
TI  - Developing asthma in childhood from exposure to secondhand tobacco smoke:
      insights from a meta-regression.

PMID- 18813632
TI  - [The relevance of qualitative techniques in biomedical research].
AB  - On observing how qualitative and quantitative studies are reported in the
      biomedical literature it becomes evident that, besides the virtual absence of the
      former, they are presented in different ways. Authors of qualitative studies seem
      to need almost invariably to explain why they choose a qualitative approach
      whereas that does not occur in quantitative studies. This paper takes Ludwik
      Fleck's comparative epistemology as a means of exploring those differences
      empirically, illustrating on the basis of two studies dealing with different
      aspects of biomedical practices how qualitative methods can elucidate a variety
      of questions pertaining to this field. The paper concludes presenting some
      structural characteristics of the biomedical field which on one hand, would not
      be explored properly without employing qualitative methods and, on the other
      hand, can help understanding the little value given to qualitative techniques in
      this area.

PMID- 18813633
TI  - [Skin cancer: use of preventive measures and demographic profile of a risk group
      in the city of Botucatu].
AB  - The aim of this paper was to establish the demographic profile of an at-risk
      group for skin cancer and to assess the preventive measures taken by the studied
      individuals and by the employer. The methods chosen was a quantitative study with
      a sample of 33 mail carriers from the Empresa Brasileira de Correios e Telegrafos
      in Botucatu, Brazil. Information regarding the demographic profile, how long the
      individual had been working for the company, hours of sun exposure, history of
      sunburns, family cancer history and skin cancer prevention strategies used by the
      company was collected by means of a questionnaire. The data were analyzed using
      Fisher's Exact Test at a 5% probability. The predominant age groups were 26-30
      and 31-35 years corresponding to 42,42%. The predominant skin color was white
      (93,94%) and 81,82% of the studied individuals were working in the company for
      over five years. 63,63% of the interviewees use sunscreen habitually; those who
      do not explain this with a lack of habit (in 75% of the cases). As refers to
      supply of protective equipment by the company, 100% of the subjects answered
      positively. These findings allow characterizing the studied population as a skin
      cancer risk group. Prophylactic measures in form of educational actions for
      awareness building should be adopted and stimulated.

PMID- 18813634
TI  - [Demographic and epidemiological characterization of men with prostate cancer].
AB  - This study aimed to identify the demographic and epidemiological characteristics
      of men with prostate cancer, assisted at the Botucatu School Hospital/UNESP
      between January 1, 2000 and January 31, 2003. The data collected from 78 of 94
      medical records included educational level, tobacco use, marital status, year of
      birth, diagnosis and symptoms. A quantitative method associated with descriptive
      statistics was used to this purpose. 50% of the patients had not concluded
      elementary school, 27.39% were non-smokers, 87% were married, 43% were aged 64-73
      years, 27.58% were diagnosed in 2000, 63.2% were retired, 20.7% showed weak urine
      stream as a symptom. Only 20% had undergone preventive exams and 77.9% had not
      completed elementary school. Prostate cancer accounted for 7.34% of the cancer
      cases, showing an incidence of 73,4/1000. The study was conducted in this
      hospital for being a tertiary reference unit in the DIR XI(1). 80% of the
      patients sought care when symptoms of the disease were already present. This
      makes us believe that the population still lacks information about prostate
      cancer, mainly as refers to incidence and prevalence related to age as a risk
      factor. This study will contribute to improving the care delivered to these
      patients including early diagnosis and possible cure, thus improving their
      quality of life.

PMID- 18813635
TI  - [The work in oral health of the Community Health Agent in Family Health Units].
AB  - The present study aimed at understanding the work of the Community Health Agent
      (CHA) in the field of Oral Health in Brazilian Family Health Units (FHU) in 2005.
      This study represents a qualitative approach to the meanings and feelings that
      underlie the know-how in Oral Health of the CHA, showing his experience in this
      process. The sample consisted of nine CHAs from two Family Health Units. Data
      were collected in interviews with four guiding questions. The statements were
      analyzed using discourse analysis. It was observed that the CHAs recognize the
      importance and demand for more qualification and re-qualification opportunities
      enabling them to overcome the feeling of limitation expressed in their discourse.

PMID- 18813636
TI  - [The managerial practice of the nurse within the FHP (Family Health Program) from
      the perspective of his/her educational and pedagogical action: a brief
      reflection].
AB  - This article deals with the educational and managerial actions of nurses in the
      Family Health Program (FHP). It traces the reality of the FHP within the
      institutional setting of the city of Natal/RN, raises some questions and analyzes
      the educational action of the program in the daily routine of the Health Units in
      the light of the literature. Its objective is to contribute to the reflection
      about the managerial action of the nurse in that setting, in connection with
      pedagogical and educational action. The study demonstrates that, as a result of
      its innovative nature, the Family Health Strategy is facing challenges such as
      the need to define the profile of competencies for these professionals, their
      qualification processes, continued and permanent education, and new managerial
      models for nursing that should specifically meet the daily demands.

PMID- 18813637
TI  - [Stones crushing lives: victims and their widows in the marble industry in Itaoca
      (ES)].
AB  - This text based on an ethnographic survey presents the social impact on the
      families of victims of fatal work accidents in the ornamental stone industry in
      Itaoca, district of Cachoeiro de Itapemirim, Espirito Santo, Brazil. The
      following elements are analyzed: family culture; living with fatal accidents;
      experiences of family grief; the way the companies and the union deal with worker
      rights; material, symbolic, and emotional resources used by the families to face
      hardship caused by accidents. Authoritarian management appealing to masculinity
      and improvisation are factors that favor work accidents. The need to earn their
      living, the fact of valuing work as an attribute of honorableness and lack of
      options render the workers subject to domination. Most of the widows are highly
      religious and receive emotional, symbolic and material support from their
      families, the community and the union. There is a notable lack of concern and
      support for the families on the part of managers and public institutions.
      Advances in the organization of the union and improvement of the working
      conditions forced by the demands of export buyers have occurred recently.

PMID- 18813639
TI  - [The contradictions between the universal Unified Health System and the transfer
      of public funds to private health plans and insurances].
AB  - Trailing the whole group of trends and changes in the scenario of relations
      between the public and the private, this article analyses the effects of the rise
      in the rates of return of health plan operators and health insurance companies in
      2007. Special attention is given to the segmentation of the system, the
      complaints about the naturalization of inequitable access to health services and
      to the depreciation of the original concepts of the Unified Health System. The
      study also gathers information regarding the production of knowledge about
      supplementary care with the intent to systemize the bases and methodological
      approaches adopted by a selected sub-group of scientific papers. Finally, the
      article develops conjectures and hypotheses with regard to possible associations
      between growth and stability of the health plan and insurance market and as
      refers to the nature of scientific production about this issue, taking into
      consideration the contradictions between the political and economical circuit in
      which the health plan and insurance companies are operating and the universality
      of the Brazilian Health System.

PMID- 18813640
TI  - [The private health insurance market: did the problem become a solution?].

PMID- 18813641
TI  - [The public-private mix in the Brazilian health system: cognitive and analytical
      obscureness].

PMID- 18813642
TI  - [Interfaces between the management of the Unified Health System and the
      regulation of private health plans].

PMID- 18813644
TI  - [Capital accumulation patterns: capital and services in the current
      transformations of the health system].
AB  - The purpose of this article is to introduce elements of the capitalist society
      economic reproduction to the discussion around the current dynamics of health
      accumulation. It identifies the direction and significance of capital
      accumulation in the health area as well as the characteristics of the economic
      environment where the competition currently takes place. The hypothetic
      hypertrophy of the financial sphere is seen as a means for structuring the
      capitalist economy since the late twentieth century. The former delimitations
      between industrial production and service delivery are blurred and weakened; the
      competition process shows new features and the contradictions - internally
      between the different elements of the health industry and externally with other
      sectors - are changing. This article aggregates elements for a contemporary
      analysis of the "medical-industrial complex" on the basis of a theoretical
      historical-conceptual approach. We identify changes in the capital dynamics of
      this complex at international and national level and stress the increasing role
      of the health services as a forefront of capital accumulation. The new approach
      is based on the economic thinking of Marx in addition to the current discussions
      about the theory of financial capital accumulation and the new productive
      configurations of the large corporations.

PMID- 18813645
TI  - [The current situation of the private health plans and insurance market in Brazil
      and trends for the future].
AB  - This paper presents an overview of the Brazilian private health plan market over
      the period 2000-2006. The current situation is analyzed with respect to the
      profile of private insurance companies, health plans and beneficiaries and some
      possible trends that were identified in the study are emphasized. The increase of
      employer group-plans as a work-related benefit and the reduction of individual
      plans are discussed. Although the market is restricted to only a few companies,
      there are more people covered by local plans than by plans offering coverage on a
      national basis. Finally, the paper approaches aspects related to the financial
      resources, among them the governmental incentive for the health area, and points
      to the need of further studies for a better understanding of the supplementary
      healthcare market.

PMID- 18813646
TI  - [The public-private mix in the Brazilian Health System: financing, delivery and
      utilization of health services].
AB  - This paper analyzes the public-private mix in the Brazilian Health System from
      the perspective of health care delivery, utilization and financing. Moreover,
      this quantitative study based on secondary data from official databases
      contemplates the subsidies granted by the government to the private sector. It
      shows the existence of some inequalities favoring the population having private
      health plans, a result of the peculiar participation of the private sector in the
      Brazilian Health System not only offering supplementary care but duplicating the
      coverage offered by the public system (called SUS). The analysis is made on the
      basis of the classification of public-private mix in Health Systems developed by
      the OECD in 2004, that helps understanding the kinds of inequalities occurring in
      each type of public-private mix. The inequalities that occur in the Brazilian
      system must be understood as the result of the duplicated coverage offered by the
      private market and of the weak public funding for the SUS while granting
      important subsidies to the private sector.

PMID- 18813647
TI  - [Compared supplementary healthcare policies in the context of public health
      systems: European Union and Brazil].
AB  - This paper analyzes the supplementary healthcare policies adopted in recent years
      in Brazil and in European countries. The proposed approach is a comparative
      analysis of the private health plan and insurance policies in the context of the
      European Union and Brazilian public health systems. This comparison allowed
      establishing parameters and categories capable of showing the differences and
      similarities between these experiences. These variables served as a basis for
      analyzing the Brazilian case using recent results of studies on private health
      insurance in the context of the Unified Health System (SUS), the Brazilian Public
      Health System. The main topics investigated were: the contracts and agreements
      between the public and the private sector, the attributions of the private health
      care services in the public system, the production, available capacity and
      financing of the public and private health systems and finally, the regulations
      regarding reimbursement of the SUS in those cases, where users covered by the
      private sector made use of the public services. We conclude retaking the
      discussion of the theoretical and conceptual perspective in the comparative
      analysis of health system policies based on the insights originated by this work.

PMID- 18813648
TI  - [The regulatory regime and the health insurance industry in Brazil].
AB  - This paper analyzes the regulatory regime for health insurance and prepayment
      schemes in Brazil. It describes the ideas that have influenced the creation of
      the Agencia Nacional de Saude Suplementar-ANS (National Agency of Supplementary
      Health) in 2000, showing that the independent agency model was a direct result of
      the privatization process and of the induction of new competition mechanisms in a
      natural state monopoly. The paper concludes that the prepayment firms in Brazil
      are facing a new institutional environment as refers to their market entry or
      exit conditions.

PMID- 18813649
TI  - [Regulation of supplementary health care: an analysis of the main results].
AB  - This article analyzes some recent results of the regulation of supplementary
      care, particularly in the period 2000-2006. Three analytical axes were defined:
      the structure and operation of the sector, the economic regulation and the care
      model regulation. Indicators were used to analyze the evolution of these three
      aspects. We come to the conclusion that the adopted regulatory measures brought
      important advancements in the analyzed dimensions, markedly a greater solidity of
      the health plan operators and the growth of the sector over the period with an
      increase of about 30% in the number of beneficiaries. The regulatory measures
      regarding the care model were innovative and revealed appropriate for inducing
      new care practices focused on health promotion and disease prevention as well as
      the introduction of quality assessment mechanisms (Qualification Project).
      However there is still ground for improvement: in the discussions about the
      public-private relation; in changes in the care model in the sense of reducing
      fragmentation of services and assuring integrated care, health promotion and
      disease prevention; and with respect to competition in the sector.

PMID- 18813650
TI  - [Procedures and perceptions of professionals and groups acting in the Brazilian
      health plan market].
AB  - This study analyzes the mechanisms used in Brazil by health plan and insurance
      operators, hospitals and physicians for organizing the access to health care
      services and their strategies towards cost reduction and decision-making. The
      study is based on the literature about regulation of the health services, with
      special focus on micro-management and managed care. From an intentional sample of
      health care organizations selected according to the number of beneficiaries,
      organizational modality and geographic criteria we selected probabilistic samples
      of doctors and hospital services. Data were collected through questionnaires
      applied to key informants from health care operators and affiliated doctors and
      hospitals. Results suggest that the relationships between health care
      organizations, physicians and hospitals follow basically patterns inherited from
      the former social security system, mainly with fixed pricing and open account
      payments. More complex financing mechanisms, risk sharing and efficiency
      strategies are of minor interest. Mechanisms for risk reduction and encouragement
      of adequate use of technologies are weak. Cost control is mainly based on co
      payment and barriers to access to the services. We conclude that in Brazil
      managed care is still in its beginning.

PMID- 18813651
TI  - [Evaluation experiences of the supplementary care sector: contributions of
      integrality].
AB  - This work identifies aspects of comprehensiveness in the proposals for healthcare
      evaluation of the Agencia Nacional de Saude Suplementar (ANS) in Brazil, and of
      the National Commitee Quality Assurance (NCQA) in the U.S.A. The investigation
      was based on a documental analysis of the proposals found in the websites of both
      institutions in the second semester of 2006. The data were systemized according
      to pre-established attributes, building an analytical matrix for evaluating the
      following three dimensions: management practices and service organization;
      quality of knowledge and of practices of the health workers; and quality of the
      control practices of the society. In the Brazilian case there was an emphasis on
      the first and the third dimensions. The evaluation focalized the operators; the
      health plans were not evaluated. In the American case there was a balance between
      the three sets of attributes and the evaluation was focused on the health plans.
      Both proposals measured the satisfaction of the beneficiaries and made the
      results of the evaluations available in their websites. In conclusion we
      emphasize the importance of evaluative concepts and approaches for measuring the
      integrality of private health plan operators in the Brazilian supplementary
      health sector.

PMID- 18813652
TI  - [The public-private mix and health service utilization: a study of the
      therapeutic itineraries of Brazilian supplementary care beneficiaries].
AB  - This study analyzes the health-disease-care experience reported by users of the
      Brazilian supplementary system in cardiovascular, oncological, mental health and
      obstetric care in Florianopolis, capital of the state of Santa Catarina. It
      discusses the selection of indicators in these areas such as myocardial
      infarction, breast cancer, alcoholism and childbirth besides exploring socio
      anthropological contributions to the management field. The results show a search
      for solutions in three interconnected sub-sectors of the system - the
      professional sector, the popular sector and the folk sector, the two latter being
      of greatest importance in mental and oncological care. Combined use of public and
      private services appears in cardiovascular and oncological field. Seeking to
      overcome the gaps with respect to access and integrality by using their own
      choices with respect to accessibility and comprehensiveness of care by using
      paths or strategies the users establish a variety of arrangements in their
      everyday life. The socio-anthropological approach is therefore useful for
      deepening the understanding of the meaning of public and private in health
      systems as well as of the care models undertaken by the patients.

PMID- 18813653
TI  - [Home health care in supplementary care: a device for a productive
      restructuring].
AB  - This study discusses the role the Brazilian Home Health Care Program (Programa de
      Atencao Domiciliar - PAD) plays in supplementary care using the example of a
      Group Care provider headquartered in Rio de Janeiro. The purpose of the study was
      to understand how home health care is produced by verifying the interaction
      between the medical team, beneficiaries and family members considering that the
      service in this care model is delivered in the micro-political scenery of the
      process, in the client's own home. The assessment of this program must consider:
      infrastructure and logistics, beneficiary eligibility criteria, the care-network
      formed in support of the PAD and above all the work process. Especially the
      latter is a strong indicator, in the present case characterized by an eminently
      multi-professional team operating in networks with integrated therapeutic
      projects. For the professionals, Home Health Care has the meaning of an
      innovative and highly valuable approach to care delivery. The article concludes
      considering the PAD an important device for a fruitful restructuring of
      supplementary care through different ways of care delivery.

PMID- 18813654
TI  - [The decision of women for cesarean birth: a case study in two units of the
      supplementary health care system of the State of Rio de Janeiro].
AB  - Cesarean section rates are very high in Brazil mainly in private hospitals,
      probably due to socioeconomic and cultural factors. The objective of this study
      was to describe socioeconomic, demographic, cultural and reproductive
      characteristics of women in the postpartum period and the factors that had
      determined their decision for caesarean section in two units of the supplementary
      health care system of the State of Rio de Janeiro. The study population was
      composed of 437 women that had vaginal or caesarean childbirths in the two
      selected units. Data were collected by means of interviews with mothers and
      consultation of hospital records. The factors associated with the decision for
      cesarean section as mode of delivery were evaluated using non-conditional
      logistic regression analysis and following the hierarchic models established at
      three definite moments. Although 70% of the women had no initial preference for
      cesarean section, 90% of them had this mode of birth. It was verified that,
      despite their initial desire, the interaction with the health services resulted
      in cesarean section as mode of birth. Educative actions directed to pregnant
      women and to the public at large as well as changes in the childbirth care model
      can be promising strategies for reverting this picture.

PMID- 18813655
TI  - [Care models in the supplementary care system: the case of a self-management
      operator in Brazil].
AB  - This paper analyzes the care model employed by a self-management operator in
      Brazil. The investigation was carried out in form of a case study. Different
      actors, managers of the Operator and the Call Center and affiliated hospitals and
      physicians, were interviewed for collecting data about the care model provided.
      The in depth analysis of the interviews used the following analytical dimension
      for evaluating the collected data: objective of the actors, instituted policies,
      instituted technological knowledge, organizational form and offered care.
      Differently from the market logic, the investigated self-management operator
      showed not profit-driven in its operations but seeks market strategies such as
      capturing new clients, adopting regulatory measures and controlling introduction
      of new technologies to ensure his survival. The operator has encouraged health
      promotion and client bonding. These results refer exclusively to the analyzed
      operator and do not apply to the existing operators in general.

PMID- 18813656
TI  - [Time of adhesion to the Family Health Strategy protects elderly against
      cardiovascular and cerebrovascular accidents in Florianopolis, 2003 to 2007].
AB  - The Family Health Strategy (FHS) provides longitudinal follow-up and integrated
      healthcare. This study evaluated the influence of the time of adhesion to the FHS
      upon the incidence of cardiovascular and cerebral vascular accidents among the
      elderly enrolled in the CASSI-Florianopolis. The events were selected because of
      their high incidence, good notification and association with risk factors the FHS
      is able to modify. The longer the time of adhesion to the strategy the lower the
      incidence of these events, demonstrating the effectiveness of the FHS. A
      historical cohort study was conducted with 674 senior participants (60 or more
      years), registered between November/2003 and March/2007. The analysis used
      Student's T test, bivariate and multivariate analysis with logistic regression.
      The independent risk factors were: age over 80 years, (OR=3,44; CI 95%: 1,8-6,2),
      diabetes (OR=2,62; CI 95%: 1,4-4,7), hypertension (OR=1,68; CI 95%: 1,0-2,6) and
      physical inactivity (OR=2,06; CI 95%: 1,2-3,2). The study found no significant
      association between gender, dislipidemia, obesity, smoking, alcoholism and the
      studied events. The long time of adhesion to the FHS showed independent
      protective effect (OR=0,43; CI 95%: 0,2-0,8) after adjustment to earlier
      covariates, being effective in reducing the incidence of cardiovascular and
      cerebral vascular accidents among the enrolled population of elderly.

PMID- 18813657
TI  - [Factors associated with the use of clinical guidelines by health plan operators
      and their inpatient care providers].
AB  - This paper is aimed at identifying factors related to the use of clinical
      guidelines by health plan operators and their inpatient care providers in the
      supplementary care sector in Brazil from the viewpoint of managers. The study is
      based on two national surveys: one involving 90 health plan operators randomly
      selected from a universe of 1573, oriented towards characterizing the
      implementation of clinical guidelines and other tools of clinical governance; and
      another involving 74 hospitals, selected from a universe of 3817 inpatient care
      providers, aimed at capturing micro-regulation mechanisms applied by health plan
      operators and their repercussions on hospital practices. Use of clinical
      guidelines was reported by 32.3% of the health plan operators, and 51.6% of the
      hospitals interviewed. Among the first, geographical location, type and size of
      the organization were independently associated with use of clinical guidelines
      while among the hospitals size, complexity and use of other tools of clinical
      governance were independently associated with the dependent variable. The results
      show how incipient and unsatisfactory the intervention of the health plan and
      hospital managements still is with regard to the quality of health services
      offered to the beneficiaries.

PMID- 18813658
TI  - [Imaginaries present in the training of health professionals in Brazil and the
      horizons of supplementary care regulation].
AB  - This paper is part of a research into the imaginaries present in the training of
      health professionals with respect to the regulation and exercise of their
      profession. The professions selected were medicine, odontology and psychology,
      for which emerging courses require evaluation by the National Health Council. The
      imaginaries were understood as operators of the virtual and the real with the
      potential of affirming or denying forms and contents in relation to being a
      professional or being in the profession. There was evidence for an imaginary of
      free exercise of the profession in the public sector on state level, where more
      experience with diseases and diversities of suffering would be gained. The ideal
      work place would be the private sector allowing for free choices for both
      professionals and users, but not without connection to the public sector for
      providing experience, study opportunities and the possibility of research
      scholarships and overseas training. Despite the expectations in relation to the
      private sector, currently there is no education in the field of supplementary
      care or about the meanings of the regulation proposed by the Brazilian Health
      System.

PMID- 18813659
TI  - [Professional strategy and institutional isomorphism: the dental health insurance
      industry in Brazil].
AB  - This article analyzes the organizational model of the dental health industry. The
      main organizational leaders in this industry are the professional cooperatives
      and group dental insurance companies. The theoretical basis of the article is the
      organizational theory developed by Di Maggio and Powell. The dental health
      industry consists of a great number of small and very dynamic companies, however
      an expressive part of clients and profit are concentrated in a few large
      companies. The results show that the industry has expanded the number of clients
      after the creation of the National Health Insurance Agency. The regulation regime
      has forced institutional changes in the firms with regard to the market entry,
      permanence or exit patterns. There was no evidence that the regulatory rules have
      interfered with the development and financial conditions of the industry. The
      average profitability of the sector, especially among the group dental insurance
      companies, is extremely high.

PMID- 18813660
TI  - [Health care plans: interfaces between the public and private system in the
      dental sector].
AB  - The present work presents a brief history of health plans in Brazil examining the
      interface between the public and the private sector. The evolution and regulation
      of the supplementary care system is analyzed, the different care modalities are
      defined and the main differences between health plans and dental care insurance
      are pointed out. The coverage provided by the supplementary care system and its
      relationship with the public health system is shown on the basis of current data.
      On the other hand, the study focuses on the care services, health plans and the
      labor market in the sector correlating, also on the basis of current data, the
      challenges and new opportunities of the supplementary care market, mainly in the
      dental sector. Although the dental sector is living an extraordinary moment
      within the private health care system and given that ANS data are pointing to a
      growth of this sector of 210% over last the 7 years, the service coverage of the
      supplementary care sector mainly directed to medical and inpatient care does not
      meet the real demand for integrated health care.

PMID- 18813661
TI  - Testicular dysgenesis syndrome and the estrogen hypothesis: a quantitative meta
      analysis.
AB  - Male reproductive tract abnormalities such as hypospadias and cryptorchidism, and
      testicular cancer have been proposed to comprise a common syndrome together with
      impaired spermatogenesis with a common etiology resulting from the disruption of
      gonadal development during fetal life, the testicular dysgenesis syndrome (TDS).
      The only quantitative summary estimate of the link between prenatal exposure to
      estrogenic agents and testicular cancer was published over 10 years ago; other
      reviews of the link between estrogenic compounds, other than the potent
      pharmaceutical estrogen diethylstilbestrol (DES), and TDS end points have
      remained inconclusive. We conducted a quantitative meta-analysis of the
      association between the end points related to TDS and prenatal exposure to
      estrogenic agents. Inclusion in this analysis was based on mechanistic criteria,
      and the plausibility of an estrogen receptor (ER)-alpha-mediated mode of action
      was specifically explored. Eight studies were included, investigating the
      etiology of hypospadias and/or cryptorchidism that had not been identified in
      previous systematic reviews. Four additional studies of pharmaceutical estrogens
      yielded a statistically significant updated summary estimate for testicular
      cancer. Results of the subset analyses point to the existence of unidentified
      sources of heterogeneity between studies or within the study population.

PMID- 18813662
TI  - [Financial capital versus medical-industrial complex: challenges for the
      regulatory agencies].
AB  - This article presents the structural processes that consolidated under the
      hegemony of the financial capital in the 90s; the dispute between the financial
      capital operating in the health sector and the medical-industrial complex; the
      strategies used by the medical-industrial complex for regaining positions; and
      the challenges all these processes pose for the regulatory agencies. The problems
      the regulatory agencies are facing lie in two central processes: 1) the hegemony
      the financial capital reached in the 90s in the health sector through reforms
      aimed at deregulating the sector in order to facilitate its entrance; and 2) the
      repositioning of the medical-industrial complex since the mid 90s by radicalizing
      medicalization. This article is based on several studies conducted by the author
      using qualitative methods and quantitative secondary data for understanding the
      historical-situational context. The theoretical approach was based on Marx,
      Gramsci, Benasayag, Badiou, Testa and Merhy. The analyses of the most recent
      reforms induced by the medical-industrial complex were the result of a
      bibliographic and document review.

PMID- 18813663
TI  - [Control of carotenoid loss in vegetables prepared in a hospital foodservice].
AB  - The aim of this study was to assess the handling procedures of kale and tomatoes
      in a hospital foodservice (HFS) in order to control loss of beta-carotene and
      licopene. The adopted measures, up to then not used by the HFS, were: 24-h
      storage under refrigeration (10 degrees C), hygienizing for 15 min and
      distribution immediately after preparation. Vegetable samples were collected
      after reception and after each stage of manipulation in the HFS. The samples were
      analyzed using high performance liquid chromatography (HPLC) with a mobile phase
      of methanol, ethyl acetate and acetonitrile (50:40:10). ANOVA (alpha = 0.05) was
      used to detect significant differences. No significant differences in the content
      of the components were found between the different stages of manipulation but
      there was an important decrease in the retention rates. In kale a retention rate
      of 68.2% for beta-carotene was verified 60 minutes after preparation whereas in
      tomatoes 91.96% of this compound were preserved for 120 minutes after
      preparation. No important decrease was observed in the retention of licopene. The
      high retention rates showed that the evaluated procedures contributed to control
      the loss of carentoids in vegetables and therefore these measures should be
      adopted in other HFS.

PMID- 18813664
TI  - [Evaluation of emergency hospital services in the state of Rio de Janeiro].
AB  - This study aimed at the evaluation of urgency/emergency hospital units and
      recorded the relations of emergency units with users, other hospital services and
      the healthcare network and approached the size of the teams, the relations among
      the professionals, their qualification and income. It further describes the
      infrastructure of these services including basic organizational aspects. The
      aspect care was one component in this broader object. It is a descriptive study
      applying a questionnaire to the heads of the emergency services of a sample of 30
      hospitals.The statements suggest the overcrowding of emergency services (in 80%
      of hospitals) deteriorating the work and care conditions to be due to the
      inefficiency of primary care and the healthcare network. The deficit of human
      resources was found larger than the lack of technology. The precarious employment
      relations were considered a factor hampering the qualification and retention of
      professionals. The most favorably evaluated items were: relationship with service
      heads, trust and expectations with regard to the service. The worst items were:
      wages, team size and labor medicine. The nvestment in human resources is
      indispensable. There is a need for public policies that articulate more efficient
      interventions given that those in force are defining the configuration of
      territories with their hierarchized and solidary networks.

PMID- 18813665
TI  - [Migrations forced by violence: the Colombian case].
AB  - The human migrations have been one of the motors in the history of humanity.
      During the twentieth century, internal forced displacement has been an important
      component of the migration processes in the world. Colombia, a paradigm for this
      phenomenon, is a country with more than three and a half million people displaced
      over the last 25 years by force of the violence resulting from an internal armed
      conflict. Besides the socio-demographic effects in the reconfiguration of the
      cities, this problem affects the human condition of the victims deteriorating
      their health and quality of life. This article aims to show the general panorama
      of migrations forced by violence in the world and to analyze the peculiarities of
      this phenomenon in the Colombian case. We conclude that forced displacement is a
      serious violation of human rights producing a human drama by exposing the
      affected individuals and communities to vulnerability and a deep deterioration of
      their quality of life and health.

PMID- 18813666
TI  - [Prevalence of overweight and obesity among members of the Brazilian army:
      association with arterial hypertension].
AB  - This study was aimed at determining the association between body mass index
      (BMI), waist/ hip index (WHI) and waist circumference (WC) with prevalence of
      systemic arterial hypertension (SAH) in male members of the Brazilian Army. The
      sample consisted of 426 men aged between 27 and 37 years, all students of the
      Brazilian Army Post Graduation School for Officers - EsAO in 2006. Subjects were
      considered hypertense when presenting arterial pressure equal or above 140/90mmHg
      and when using antihypertensive drugs. Considering the BMI, WHI and WC
      respectively, the results point to the following percentages of obese or
      overweight subjects: 12.91%, 7.98% and 17.84%. The best anthropometric indicator
      for systemic arterial hypertension was the waist/ hip index (Odds Ratio = 4,45).
      Our findings show a prevalence of systemic arterial hypertension (5,63%)
      considerably below that found in other national studies and strong associations
      between the used anthropometric indicators and hypertension.

PMID- 18813667
TI  - [Analysis of the oral health care model in cities of the state of Pernambuco].
AB  - The objective of this study was to analyze the oral health care model in nine
      cities of the state of Pernambuco on the basis of statements of the Oral Health
      Primary Care Coordinators. Semi-structured interviews were conducted with the
      coordinators for collecting data about the oral health care model adopted by the
      local authorities, about their activities as coordinators, their qualification,
      the practices developed by the dental surgeon making part of the Family Health
      Team, and about basic care procedures and reference and counter-reference
      networks. The data collected in the interviews were evaluated using a qualitative
      methodology and a matrix was created for classifying the cities according to the
      profile of their professionals and the actions and services offered. The results
      showed that among the analyzed cities three fitted into the category
      "structured", five into the category "semi-structured" and only one was
      considered "not-structured". This indicates that the greater of the cities is
      facing difficulties in structuring oral health care, mainly as refers to
      incorporation of new care practices and to the professional qualification of
      dental surgeons and oral health coordinators.

PMID- 18813668
TI  - [Salmonella spp., important pathogenic agent transmitted through foodstuffs].
AB  - The occurrence of foodborne diseases has been a matter of discussion over the
      last years due to the worldwide concern with strategies for their control and for
      ensuring that safe food products reach the consumer. Salmonella spp. is among the
      most widespread microorganisms in nature, having man and animals as main natural
      reservoirs. With occurrence of regional serotypes causing salmonellosis, this
      pathogen is considered one of the main agents responsible for outbreaks of
      foodborne disease in the developing countries. The increasing incidence of
      salmonellosis caused by contaminated food has shown that, despite the recent
      technological improvements, this problem still occurs in all countries. Cattle
      and poultry are the main responsible for the transmission of this pathogenic
      agent. Due to its wide distribution in animals, the existence of asymptomatic
      carriers and its presence in foodstuff and in the environment Salmonella spp.
      represents a significant public health problem worldwide calling for permanent
      control programs and eradication strategies.

PMID- 18813671
TI  - Psychiatric reform in Brazil: helping build and strengthen the Unified National
      Health System.

PMID- 18813672
TI  - [Terminology for drug incidents in the hospital context].
AB  - In-hospital drug incidents cause problems for patients and additional costs for
      the health system. The variety of terms used to report them leads to disparities
      in research results and confuses the professionals that report them. This study
      aimed to review the terms used to describe drug incidents by collating them with
      the official concepts and definitions. PubMed, MEDLINE, IPA, and LILACS were
      searched to select studies published from January 1990 to December 2005. Thirty
      three publications were selected. The supranational terminology recommended for
      describing drug incidents proved insufficient, but there was consensus that the
      expressions are used as a function of the type of incident. Adverse drug reaction
      is used when no intent is identified. Adverse drug event mainly describes
      incidents during hospitalization, and drug-related problem is used in studies on
      pharmaceutical care (use or lack of the drug). Still, the division between these
      categories is neither clear nor simple. Future studies on the relations between
      categories and multidisciplinary research on human error could support proposals
      for new concepts.

PMID- 18813673
TI  - [Oral cancer epidemiology in a public laboratory in Mato Grosso State, Brazil].
AB  - This study analyzed oral cancer epidemiology based on histopathology reports from
      a public laboratory in Mato Grosso, Brazil, after a specific policy was
      implemented for treating oral and facial diseases in the State. This was a cross
      sectional epidemiological study, based on 1,324 histopathology reports issued
      from January 2005 to December 2006. The study identified 44 cases of oral cancer,
      or 3% of all oral lesions, and analyzed them in relation to the following
      variables: histological type, gender, age, and patient's place of residence
      (capital versus rest of State). The most common histological type was squamous
      cell carcinoma. Most of the diagnoses occurred in men in their 50s and 60s living
      in the interior of the State. During two years in operation, this public oral
      pathology service had recorded a considerable number of oral cancer cases.

PMID- 18813674
TI  - [Accidents with foreign bodies in children under 15 years of age: epidemiological
      analysis of first aid services, hospitalizations, and deaths].
AB  - This study aims to analyze accidents involving foreign bodies among children less
      than 15 years of age residing in Londrina, Parana State, Brazil, in terms of
      first aid, hospitalization, and death (2001). Data were obtained from general
      hospital records and the Municipal Mortality Database. A total of 434 accidents
      were analyzed, with a 3.7% hospitalization rate and 0.7% mortality. Boys
      predominated (53.7%), and the incidence rate was highest among children one to
      three years of age (7.2 per 1,000 children). Foreign body penetration in natural
      orifices (eyes, nostrils, and ears) accounted for 94%, inhalation/ingestion of
      food 2.8%, inhalation/ingestion of objects 2.5%, and aspiration of gastric
      contents 0.7%, and these causes accounted for all the deaths. The results
      contribute to epidemiological knowledge on such accidents and indicate the need
      to restructure health services in order to decentralize care for less complex
      injuries, besides emphasizing the need for preventive measures.

PMID- 18813675
TI  - [Oral hygiene habits and use of dental services among teenage students in a city
      in southern Brazil].
AB  - This study evaluated oral hygiene habits and use of dental services among teenage
      students, and analyzed their association with sociodemographic factors and life
      styles. This cross-sectional study included a representative sample of 1,170
      seventh-graders from municipal public schools of Gravatai, Rio Grande do Sul
      State, Brazil. The Cox regression model for univariate analysis, modified for
      cross-sectional studies, was used to analyze the association between variables.
      Of the adolescents included in the study, 77.8% brushed their teeth three or more
      times a day, 31.9% flossed daily, 68.9% visited the dentist regularly, and 50%
      visited the dentist for dental treatment. Tooth brushing was more frequent among
      female adolescents. Lower socioeconomic status was associated with a lower
      frequency of daily flossing, fewer annual dental visits, and a greater prevalence
      of dental treatment visits. Similar results were found for adolescents with a
      sedentary lifestyle or that had tried smoking. The consumption of candy was
      associated with lower frequency of annual dental visits, and the consumption of
      soft drinks, with greater frequency of treatment visits. A healthy life style was
      associated with better oral hygiene habits and more frequent dental visits.

PMID- 18813676
TI  - [Justifications for formula supplementation in low-risk newborns at a Baby
      Friendly Hospital].
AB  - The Baby-Friendly Hospital Initiative recommends not giving newborn infants any
      food or drink other than breast milk unless medically indicated. This study
      investigated the prevalence and alleged reasons for giving formula
      supplementation to rooming-in newborns at a Baby-Friendly Hospital. Participants
      were 300 formula-supplemented, exclusively rooming-in newborns at a Baby-Friendly
      Hospital in Rio de Janeiro, Brazil. Reasons for formula supplementation were
      classified as acceptable or unacceptable in accordance with the WHO/UNICEF Baby
      Friendly Hospital Initiative guidelines. A supplementation prevalence of 33.3%
      was found. The main allegations were: hypogalactia/ agalactia (36.8%), conditions
      involving risk of hypoglicemia (21.1%), cesarean section (7.9%), stomatognathic
      system-related conditions (7.4%), maternal conditions (6.3%), and absence of
      maternal HIV serology (4.5%). Cesarean section was associated with a higher risk
      of supplementation (RP = 2.1; 95%CI: 1.77-2.55) as compared to vaginal delivery.
      Supplementation prevalence was high, and only 9% of the allegations were
      justified.

PMID- 18813677
TI  - [Prevalence and factors associated with behavioral disorders in adolescents: a
      population-based study].
AB  - This study proposed to estimate the prevalence of behavioral disorders and
      associated factors in adolescents (11-15 years), using a cross-sectional design
      (n = 1,145). Subjects answered a self-administered questionnaire. Behavioral
      disorder was assessed with the Mini International Neuropsychiatric Interview
      (MINI). The study analyzed disorders in relation to gender, age, socioeconomic
      status, schooling, failure in school, religion, smoking, sedentary lifestyle,
      alcohol consumption, drug use, depression, and bullying (as victim). Ordinal
      regression was used for the statistical analysis, with a hierarchical model for
      the outcome. An estimated 29.2% of the sample presented behavioral disorders. In
      the multivariate analysis, the odds ratio for a male adolescent to present one
      additional point on the behavioral disorder scale was 2.04 (95%CI: 1.53-2.71).
      Alcohol consumption, drug use, and suffering bullying were associated with higher
      scores on the behavioral disorder scale. The findings also showed that the
      factors associated with behavioral disorder showed a strong interrelationship
      between health behaviors in adolescence.

PMID- 18813678
TI  - [Ten years of external control over water fluoridation in Chapeco, Santa Catarina
      State, Brazil].
AB  - This study aimed to analyze fluoride concentration in the public water supply in
      Chapeco, Santa Catarina State, Brazil, from 1995 to 2005 and to assess the
      effectiveness of a fluoridation quality intervention in 2003. A total of 989
      water samples were analyzed. Fluoride concentrations were classified according to
      three different criteria used in Brazil. The city conducted a political and legal
      intervention in 2003. The Prais-Winsten procedure was used to evaluate the
      fluoride concentrations over time. In the ten years, the water fluoridation
      system showed 46%, 32%, and 43% of adequate samples, depending on the criterion.
      Prior to the municipal intervention, the proportion of adequate samples was 40%,
      26%, and 36%, increasing to 63%, 49%, and 61% after the intervention, according
      to the three criteria. Fluoride concentration improved after the municipal
      intervention. On-going surveillance is recommended, including water fluoridation,
      dental caries, and dental fluorosis.

PMID- 18813679
TI  - [Caseload profile in emergency services: sentinel events for monitoring primary
      health care].
AB  - The study's hypothesis was that certain disease entities treated in emergency
      services, based on the sentinel event concept, are related to flaws in primary
      care and can be used to develop an indicator for monitoring such care.
      Quantitative and qualitative data were used on previously selected occurrences
      treated in the emergency department. Using triangulation of methods, the
      differences were verified in the frequencies of these occurrences between the
      areas of patients' residence/ primary care units and the motivations leading them
      to seek the emergency department. Distribution of the frequency of these events
      varied from 30% to 42.8%, according to the area of residence/ primary care unit
      (Chi2 = 9.19 and p = 0.027). The interviews suggested the existence of causality
      between the reason stated for seeking the emergency service and the performance
      of the primary care units. IN CONCLUSION: (1) the frequency of the selected
      occurrences was influenced by the area of residence/ location of the primary care
      unit; (2) this influence results partially from the primary care performance; and
      (3) the study instrument is simple and can help local administrators monitor the
      daily performance of primary care services.

PMID- 18813680
TI  - [Prevalence of mental disorders at a referral center for the Family Health
      Program in Santa Cruz do Sul, Rio Grande do Sul State, Brazil].
AB  - Among the ten leading causes of disability-adjusted life years, seven are mental
      disorders. Primary health care centers are crucial to public mental health
      policies, according to the World Health Organization. This study aimed to verify
      the prevalence of mental disorders among individuals seeking care at the referral
      center for a Family Health Program (FHP) team in Santa Cruz do Sul, Rio Grande do
      Sul State, Brazil, and the influence of psychiatric diagnosis on utilization of
      the health system. Of the 754 participants, 51.1% had a psychiatric diagnosis.
      Subjects with a psychiatric diagnosis showed significantly higher use of the
      health system in the previous 12 months. Mental disorders have a negative impact
      on well-being and quality of life, besides increasing the use of health resources
      due to untreated symptoms and because mental disorders contribute negatively to
      the prognosis of non-psychiatric medical conditions. These results show the
      importance of including mental health care in the FHP in Brazil.

PMID- 18813681
TI  - [Reproductive characteristics and utilization of preventive health services by
      childbearing-age women: results of two cross-sectional population-based studies
      in the far South of Brazil].
AB  - Two surveys were conducted (1995 and 2004) on women 15-49 years of age in Rio
      Grande, Rio Grande do Sul State, southern Brazil, assess patterns in their use of
      preventive health services. The sample included 1,339 women in 1995 and 1,311 in
      2004. A standardized household questionnaire covered their demographic,
      socioeconomic, reproductive, and health care-utilization characteristics. The chi
      square test was used to compare indicators in the two studies. During the study
      period, housing conditions, running water, sanitation, and schooling improved,
      but family income decreased. Mean age at sexual initiation decreased by one year,
      teenage pregnancy increased 33%, and clinical breast examination and Pap smears
      increased 48% and 30%, respectively. Overall use of contraceptive methods
      declined by 3%, but condom use increased from 8% to 21%. Efforts are needed to
      improve coverage for breast examination and Pap smears, postpone sexual
      initiation, and promote the use of contraceptive methods, especially condoms.

PMID- 18813682
TI  - [Total mercury in muscle of the shark Prionace glauca (Linnaeus, 1758) and
      swordfish Xiphias gladius Linnaeus, 1758, from the South-Southeast coast of
      Brazil and the implications for public health].
AB  - Total mercury (THg) was analyzed in muscle tissue from the blue shark Prionace
      glauca and the swordfish Xiphias gladius, obtained from the South and Southeast
      coast of Brazil, to verify compliance with current limits for human consumption.
      Samples were obtained through the REVIZEE Program and a commercial fishery in
      Itajai, Santa Catarina State. A total of 95 specimens were analyzed (48 X.
      gladius and 47 P. glauca), and correlations were checked between THg and fish
      length and weight. THg ranged from 0.13 to 2.26 microgg-1 (fresh weight), and
      there was no significant difference between the means for P. glauca, 0.76 +/-
      0.48 microgg-1 (f.w.) and X. gladius, 0.62 +/- 0.31 (Mann-Whitney test, p <
      0.05). In 16 % of samples, THg was above the limits set by the National Health
      Surveillance Agency (ANVISA), namely 1 microgg-1, and 62% exceeded the World
      Health Organization (WHO) limit of 0.5 microgg-1. The ingestion of 100 g/ day-1
      of P. glauca or X. gladius would result in a daily THg intake of more than twice
      the WHO (1990) suggested limit.

PMID- 18813683
TI  - [The costs of implementing and operating an oral health service from the
      perspective of the service and society].
AB  - The aim of this study was to assess the costs of setting up and maintaining
      dental care in the public sector. Costs were updated or depreciated according to
      the service's lifespan and were analyzed from the perspective of the service
      itself and society. According to the findings, for the service the total cost of
      setting up a dental care unit with seven rooms was BRL$860.643.67 in the first
      year, plus BRL$545,419.23 for maintenance, and clinical dental care was the most
      expensive specialty. For society, the total cost was BRL$990,065.06
      (implementation) and BRL$668,369.55 (maintenance), and the most expensive
      specialty was prevention (US$1.00 = BRL$1.62). Capital costs represented a small
      percentage of total costs for a dental care unit, but they need to be considered,
      since they can modify the results. Due to the high costs, preventive and
      promotional interventions should not be performed in the clinical setting, but
      should be replaced by broader and less expansive population-based interventions,
      since considerable sums need to be spent by the low-income population to
      participate in free public programs.

PMID- 18813684
TI  - [Definition of priority medicines for monitoring laboratory quality in Brazil:
      the interface between health surveillance and the National Drug Policy].
AB  - A key objective of the Brazilian National Drug Policy is the quality of medicines
      supplied to the population. This study aimed to set priorities for the analysis
      of the National Program for Quality Control of Medicines. The main criterion was
      the drug's presence in at least three Pharmaceutical Care Programs under the
      Ministry of Health. Additional criteria were presence on the National List of
      Essential Drugs (RENAME) in 2002 and its indication for the 20 main causes of
      disability-adjusted life years (DALY). The sources were data from the Ministry of
      Health and related legislation. The drugs were classified according to the
      Anatomical Therapeutic Chemical Classification System (ATC) of the WHO. The 13
      pharmaceutical care programs included 893 products classified in 449 different
      ATC codes. Twenty-eight drugs were considered priorities, 26 of which were listed
      on the RENAME and 12 indicated as causes of DALY. It is recommended that the
      National Health Surveillance Agency and Secretariat of Science, Technology, and
      Strategic Inputs establish an integrated strategy to guarantee comprehensive
      quality of these drugs, including laboratory quality, registration, good
      manufacturing practices, and information for health professionals and the general
      population.

PMID- 18813685
TI  - [A contribution to institutionalized health evaluation: a proposal for self
      evaluation].
AB  - In the context of measures to institutionalize the evaluation of primary health
      care in Brazil, the Ministry of Health proposed a formative and normative
      evaluation of the implementation of the project entitled Technical Capacity
      Building of State Health Departments for Monitoring and Evaluation, as part of
      the National Policy for the Evaluation of Primary Care. One of the objectives was
      to develop a self-evaluation model using the rapid evaluation method (REM). This
      article presents the stages concluded to date in the self-evaluation model,
      together with the theoretical references. The final self-evaluation proposal was
      based on a theoretical evaluation model developed for formative evaluation and
      included the principal actions proposed for State health management, with all the
      tested indicators, thus increasing the internal validity and consistency. The
      final perspective is that this instrument, used with a participatory approach as
      provided in the proposal, helps assess the extent to which the project's
      objectives and actions are achieved, while identifying situations that can
      interfere in different contexts.

PMID- 18813686
TI  - [Patterns of minor psychiatric disorders among battered women treated at an
      emergency care unit].
AB  - The aim of this cross-sectional study was to describe the patterns in minor
      psychiatric disorders among women who suffered different types of violence. Using
      a version of the Abuse Assessment Screen, face-to-face interviews were conducted
      in a cluster sample of women ages 15 to 49 years using an emergency care
      hospital. Women's mental status was assessed with a version of the Self-Reporting
      Questionnaire (SRQ-20). From a total of 273 women, 77.3% (95%CI: 78.2-82.2)
      scored 7 or more on the SRQ-20, indicating the presence of psychiatric illness.
      The findings suggest that women who had experienced more than one type of
      violence (PR = 1.31; 95%CI: 1.11-1.56) and who had been battered in the previous
      12 months (PR = 1.30; 95%CI: 1.08-1.58) were more likely to suffer minor mental
      disorders. The results show a positive association between violence and mental
      illness, suggesting the need for more effective measures in the care of victims,
      such as the creation of institutional nets to guarantee comprehensive care for
      women.

PMID- 18813687
TI  - [Lower back pain in health insurance policyholders: prevalence and associated
      factors].
AB  - A cross-sectional study was conducted with individuals of both sexes (20-59 years
      of age), all covered by the COOPERSINOS Health Care Plan of Vale do Rio dos Sinos
      University. The study aimed to determine the prevalence of lower back pain and
      associated factors in the previous three months. A self-applied questionnaire
      included socioeconomic, demographic, occupational, and lifestyle questions.
      Prevalence of lower back pain among the 775 individuals was 52.8% in the previous
      year (95%CI: 49.3-56.3) and 46% in the previous three months (95%CI: 42.5-49.5).
      Poisson regression for lower back pain in the previous 90 days showed an
      association with: (1) age 40-49 years; (2) self-reported strenuous or difficult
      work; and (3) smoking. Despite the high prevalence of lower back pain and
      difficulty in performing work activities, the pain was not disabling. Although
      29.9% of workers reported some difficulty in performing their daily or work
      related activities due to lower back pain, absenteeism was quite low.

PMID- 18813688
TI  - [Involvement of workers from municipal outpatient services in Uberaba, Minas
      Gerais State, Brazil, in the reorganization of services under the Unified
      National Health System].
AB  - This study was conducted in two specialized municipal outpatient clinics in the
      city of Uberaba, Minas Gerais State, Brazil. The study analyzes the involvement
      of professionals in their work and the reorganization of health services from
      their perspective, considering the participatory management recommended by the
      Unified National Health System (SUS). The study included nine workers with or
      without specific health training, all involved in health sector activities.
      Participants were selected according to profession or job (groups: dentistry,
      infrastructure, medicine, social work, psychology, coordination, nursing,
      pharmacy, and biochemistry), with one participant per "category" for each clinic.
      The content was submitted to structural narrative analysis. Three analytical
      categories were identified: management, involvement in work, and involvement in
      the SUS proposals. The study was not intended to generalize results on health
      workers' involvement, but it does highlight the importance of understanding the
      interaction between the management model and the reorganization of services as
      recommended under the SUS.

PMID- 18813689
TI  - [Oral health in the context of the Family Health Program: preventive practices
      targeting individual and public health].
AB  - Professional practices reflect the structuring of health services and are related
      to the underlying principles of the prevailing health care model. This study
      focused on preventive and educational practices by dentists in the Family Health
      Program in Natal, Rio Grande do Norte State, Brazil. A structured interview was
      held with 80 dentists, in addition to analysis of documents from the Outpatient
      Database of the Unified National Health System (SIA-SUS) and the Primary Care
      Database. Individual activities involving orientation for oral hygiene and
      topical application of fluoride were reported by 87.5% and 95% of dentists,
      respectively. At the collective level, all the dentists that worked in schools
      (91.2%) performed topical fluoride application, while 86.2% conducted educational
      activities. According to SIA-SUS records, preventive activities accounted for 41%
      of all procedures. Among these, topical application of fluoride gel per sitting
      and supervised brushing accounted for 24.4% and 31%, respectively. As for
      educational activities, 57.4% were held in the health care unit and 42.6% in the
      community. The findings indicate that the preventive practices focus on dental
      caries, particularly in schoolchildren, and that they need to be expanded to
      include other oral health problems.

PMID- 18813690
TI  - [Raising children with mental disabilities: mothers' narratives].
AB  - Technical advances in neonatology have increased the life expectancy of children
      with serious health problems. Many of these children experience developmental
      delay (mental disability) and require special care. The family must adapt to
      better provide for the child's needs. This study aimed to identify mothers'
      reactions and the obstacles they face to obtain what they consider the best
      treatment for their children. The study methodology was based on analysis of the
      mothers' narratives, drawing on medical anthropology and linguistics. The most
      typical plots in the narratives showed the impact of the diagnosis and the search
      for means to adapt to the child's care, as well as the difficulties encountered
      in the public health system to obtain what the mothers considered adequate care.
      The value ascribed to characters in the support network showed the importance of
      such support in these situations.

PMID- 18813691
TI  - [Use of urine lead level as an exposure indicator and its relationship to blood
      lead].
AB  - The aim of this work was to verify whether there are statistically significant
      correlation between the concentrations of lead in blood (Pb-B) and urine (Pb-U).
      Electrothermal atomic absorption spectrometry was used in the determination of
      lead concentration in biological material. Venous blood and spot urine were
      collected from workers occupationally exposed (95), adults (130) and children up
      to 15 years old (22) environmentally exposed. After a test showing significant
      differences between Pb-U and the three categories previously determined, cutting
      points for Pb-U were established to predict Pb-B values by the ROC curve. Thus,
      it is expected that Pb-B is lower than 10 microg.dL-(1) with Pb-U up to 0.55
      microg.dL-(1), whereas lead levels in blood below 27.6 microg.dL-(1) are expected
      when the amount of the metal in urine is lower than 2.05 microg.dL-(1). So, urine
      can be used to replace blood for the assessment of the occupational exposure to
      lead. However, caution is advised in the case of environmental exposure, since
      urinary lead should be used just as an estimation of the metal content in blood.

PMID- 18813692
TI  - [Socio-demographic factors and the dengue fever epidemic in 2002 in the State of
      Rio de Janeiro, Brazil].
AB  - This study analyzed the dengue fever epidemic in 2002 and the socio-demographic
      context of the State of Rio de Janeiro, Brazil, using spatial analysis and
      statistical modeling. The incidence rate was calculated for resident dengue cases
      in the State in 2002. The study analyzed associations between incidence and socio
      demographic variables and spatial autocorrelation using the Moran Global Index,
      which showed spatial dependence for both the outcome and the independent
      variables. A multivariate linear regression model was used. The variables'
      proportion of urban population, percentage of the population with running water,
      and percentage of coverage by the Family Health Program (FHP) explained 30.2% of
      the total variance in the epidemic's incidence rate. The model's residuals did
      not show spatial autocorrelation. The associations were in the expected
      direction, and the findings are corroborated by other studies that showed higher
      dengue incidence in areas characterized by growing urbanization and deficient
      running water and water supply, while highlighting the FHP as an important
      facilitator of vector control strategies.

PMID- 18813693
TI  - [Use of medication by Brazilian retirees: 2 - response rate and item completeness
      in a postal survey in Belo Horizonte, Minas Gerais State, Brazil].
AB  - This paper reports on the response rate and completeness of item response in a
      self-administered postal survey questionnaire on use of medication by retirees 60
      years or older under the Brazilian Social Security System, in Belo Horizonte,
      Minas Gerais State, in 2003. Questionnaires were sent in two rounds to 800 postal
      addresses of subjects selected by simple random sampling. The response rate was
      47.8%, and there were no significant differences in the selected characteristics
      between respondents and non-respondents, or between early and late respondents.
      For almost all socio-demographic and health variables, item omission was less
      than or equal to 5% for both the entire sample and early or late responders. For
      all the medicines used, the dose and laboratory were the main items omitted. The
      findings indicate that details on drug use should be reevaluated in self
      administered questionnaires.

PMID- 18813694
TI  - [Feeding preference of sand flies in the Amazon, Maranhao State, Brazil].
AB  - The objective of this study was to determine the blood feeding sources for sand
      flies based on the precipitin test in Buriticupu, Amazon Region, Maranhao State,
      Brazil, from July 2002 to June 2004. Single (87.6%) and double (8%) reactions and
      non-reactive samples (4.4%) were found. The presence of sand flies fed on human
      blood (6.7%) and blood of animals that are possible peridomiciliary Leishmania
      reservoirs helps explain the reporting of autochthonous tegumentary leishmaniasis
      cases in Buriticupu.

PMID- 18813695
TI  - [Elderly women dealing with institutionalization].
AB  - This study focused on institutionalization of the elderly from the perspective of
      gender studies. The aim was to understand the effects of institutionalization on
      the lives of elderly women and their strategies to deal with this situation. The
      study used a qualitative methodology and was conducted in a long-term care
      facility for the elderly, with 110 individuals from Alto Uruguai, Rio Grande do
      Sul State, Brazil. Data collection used discussion groups with ten elderly women
      participating. Content analysis was used and identified three main categories:
      the nursing home as a total institution, gender, and strategies to deal with
      institutionalization. Half of the women had chosen to live in the nursing home,
      while the others complained about their confinement to what they considered "a
      dump for old people". The gender category permeated the women's lives, which
      included domestic activities in the "home" in order to pass the time. Strategies
      to deal with institutionalization included religious rituals, handicrafts, and
      walks.

PMID- 18813696
TI  - Cooperation between regulatory authorities from developing countries in the
      evaluation of vaccine clinical trials.

PMID- 18813697
TI  - Diffusion tensor MR imaging evaluation of the corpus callosum of patients with
      multiple sclerosis.
AB  - OBJECTIVE: To evaluate the fractional anisotropy (FA) values of the normal
      appearing white matter of the corpus callosum (CC) in patients with relapsing
      remitting multiple sclerosis (MS). METHOD: Fifty-seven patients with diagnosis of
      relapsing-remitting MS and 47 age- and gender-matched controls were studied. A
      conventional MR imaging protocol and a DTI sequence were performed. One
      neuroradiologist placed the regions of interest (ROIs) in the FA maps in five
      different portions of the normal-appearing CC (rostrum, genu, anterior and
      posterior portion of the body and splenium) in all cases. The statistical
      analysis was performed with the Mann-Whitney U test and p<0.05 was considered
      statistically significant. RESULTS: The FA values were lower in the MS patients
      compared with the controls (p<0.05) in the following CC regions: rostrum (0.720
      vs 0.819), anterior body (0.698 vs 0.752), posterior body (0.711 vs 0.759) and
      splenium (0.720 vs 0.880). CONCLUSION: In this series, there was a robust
      decrease in the FA in all regions of the normal-appearing CC, being significant
      in the rostrum, body and splenium. This finding suggests that there is a subtle
      and diffuse abnormality in the CC, which could be probably related to myelin
      content loss, axonal damage and gliosis.

PMID- 18813698
TI  - Prevalence of cardiovascular risk factors among elderly Brazilians over eighty
      with ischemic stroke.
AB  - INTRODUCTION: An ischemic stroke is usually a catastrophic event, mostly in the
      elderly. Cardiovascular involvement is the leading cause of ischemic stroke in
      this age population and hence the knowledge about its risk factors is important
      for the definition of specific policies of prevention. PURPOSE: To evaluate the
      prevalence of cardiovascular risk factors in patients with age equal to or above
      80 in a hospital population with ischemic stroke. METHOD: Retrospective study of
      consecutive patients diagnosed with ischemic stroke admitted to a tertiary health
      facility. RESULTS: From September 2004 to March 2006, 215 patients were studied.
      There was a female preponderance (p<0.01). Among patients over eighty, 72% had
      hypertension and atrial fibrillation was more common among the oldest old
      (p<0.01). CONCLUSION: Hypertension and atrial fibrillation should be treated
      aggressively in the elderly. Anticoagulants should be considered more often in
      these patients.

PMID- 18813699
TI  - Seizure related accidents and injuries in childhood.
AB  - Several studies show that the risk of accidents involving patients with epilepsy
      is much higher compared to the general population. The objective of this study
      was to identify the frequency and type of seizure related injuries in children
      diagnosed with epilepsy. In addition we also assessed possible risk factors
      associated with this seizure related accidents in childhood. This study was
      conducted at the pediatric epilepsy clinic of Unicamp, from January 2005 to
      August 2006. We evaluated 100 consecutive children with epilepsy. Parents were
      interviewed by one of the authors using a structured questionnaire that included
      questions about seizure related accidents and related injuries. Forty-four
      patients reported seizure related accidents. Eighteen patients needed medical
      assistance at an emergency room due the severity of their seizure related
      accident. Forty patients reported having a seizure related accident prevented by
      a bystander. Another 14 patients reported avoiding a seizure related accident by
      luck alone. Contusions and lacerations were the most common type of lesion
      associated with seizures. Patients with symptomatic/probable symptomatic epilepsy
      and those using higher numbers of anti-epileptic drugs (AEDs) were at greater
      risk for seizure related accidents (p<0.05). We conclude that patients with
      symptomatic/probable symptomatic epilepsy and on multiple AEDs are at increased
      risk of seizure related accidents. Parents and caretakers should be even more
      cautious about risk of injury in such patients.

PMID- 18813700
TI  - Epileptiform abnormalities and quantitative EEG in children with attention
      deficit/hyperactivity disorder.
AB  - There is much controversy about the importance of the electroencephalogram (EEG)
      in assessing the attention-deficit/hyperactivity disorder (ADHD). The objective
      of this study was to assess the use of EEG and quantitative EEG (qEEG) in ADHD
      children. Thirty ADHD children and 30 sex- and age-matched controls with no
      neurological or psychiatric problems were studied. The EEG was recorded from 15
      electrode sites during an eyes-closed resting condition. Epileptiform activity
      was assessed, as were the absolute and relative powers in the classical bands
      after application of the Fast Fourier transform. Epileptiform activity was found
      in 3 (10%) ADHD children. As compared to the controls, the ADHD group showed
      significantly greater absolute delta and theta powers in a diffuse way, and also
      greater absolute beta power and smaller relative alpha 1 and beta powers at some
      electrodes. A logistic multiple regression model, allowed for 83.3% sensibility
      and specificity in diagnosing ADHD.

PMID- 18813701
TI  - Epileptic seizures and EEG features in juvenile systemic lupus erythematosus.
AB  - INTRODUCTION: Juvenile systemic lupus erythematosus is more incident in female
      affecting different systems including the central nervous system. The aim of this
      study was to check the incidence of seizures and electroencephalographic features
      in these patients. METHOD: It was analyzed all patients with juvenile systemic
      lupus erythematosus referred to the Pequeno Principe Hospital in Curitiba, PR,
      Brazil, in the year of 2007. The patients were submitted to EEG and subdivided
      into two groups according to the presence or absence of epileptic seizures. Mann
      Whitney statistical test was used. RESULTS: Forty-nine cases were included, there
      were 73.45% female, with an age between 3 and 28 years (micro=17.00 years; s=5.01
      years). Seizures (13/26.50%) were the most frequent manifestation followed by
      headache (13/26.50%) and ischemic stroke (6/12.25%). Cerebral vasculites were the
      most frequent alteration in neuroimage. The abnormalities of EEG were
      characterized by asymmetry of the electric cerebral activity, diffuse
      disorganized background activity, focal epileptiform discharges in the right
      central-temporal region, generalized paroxysmal of 3 Hz spike-waves, and bursts
      of theta-delta slowness activity in the right parietal-occiptal region. The
      statistic analysis showed no significantly difference between age of onset of
      symptoms and the risk of seizures (p 0.675) as well as between time of the
      disease and the risk of seizures (p 0.436). CONCLUSION: Neurologic
      manifestations, in special epileptic seizures, are frequent in systemic lupus
      erythematosus. Age of onset of symptoms and the time of disease did not increase
      the risk of epileptic seizures in this disease.

PMID- 18813702
TI  - Stigma scale of epilepsy: the perception of epilepsy stigma in different cities
      in Brazil.
AB  - PURPOSE: To assess the perception of epilepsy stigma in different regions of
      Brazil. METHOD: The Stigma Scale of Epilepsy (SSE) questionnaire was applied to
      people in different Brazilian urban settings. The survey was performed on
      individual basis; an interviewer read the questions to the subjects and wrote
      down the answers. The same procedure was applied to all the subjects and took
      around 10 minutes. RESULTS: 266 questionnaires were completed in four different
      towns of Brazil (Curitiba=83; Sao Paulo=47; Vila Velha=79; Ipatinga=57). The
      overall stigma score was 49.7 (median). Different scores were obtained in each
      locality. Vila Velha=42; Curitiba=49; Sao Paulo=52; Ipatinga=54 (ANOVA
      [2.262]=3.82; p=0.01). CONCLUSION: This study showed differences in the
      perception of stigma, which may depend on cultural and regional aspects. The
      concept of stigma has cultural perspectives, depending on the region and the
      context where each person lives. The understanding of this aspect of epilepsy is
      important to promote better de-stigmatization campaigns, considering the cultural
      and social differences.

PMID- 18813703
TI  - Association of lamotrigine and valproate in refractory epilepsies of children and
      adolescents.
AB  - OBJECTIVE: To evaluate the efficacy or eventual side-effects of the association
      of lamotrigine and sodium valproate in the control of refractory epilepsies.
      METHOD: A retrospective analysis of 37 children with a mean age of 12 years
      taking exclusively lamotrigine and sodium valproate. Efficacy of seizure control
      was considered satisfactory if there was a reduction in seizures>50% or total
      control. RESULTS: The association of lamotrigine and sodium valproate was
      considered satisfactory in 65% of the studied children, independent of seizure
      type. Total seizure control was obtained in 33% and 35% had an unsatisfactory
      response or remained unchanged. Primary generalized tonic clonic seizures were
      the most common type with 84% of day-time seizures having a good response to
      treatment. Side-effects were seen in 11% of patients and the most common was
      tremor. CONCLUSION: Total or satisfactory control of seizures was seen in the
      majority of patients and side-effects were uncommon.

PMID- 18813704
TI  - Insomniac children maternal sleep and mood in Sao Paulo and Barcelona.
AB  - OBJECTIVE: To evaluate sleep characteristics verifying for the presence of
      depressive symptoms in mothers of insomniac children living in Sao Paulo (Brazil)
      and Barcelona (Spain). METHOD: Forty-six mothers were evaluated, 37 from Sao
      Paulo and nine from Barcelona, their ages varying from 19 to 44, and their
      children; otherwise healthy but with complaints of insomnia, their age varying
      from three to 33 months. The mothers' sleep quality was rated by the Pittsburgh
      Sleep Quality Index (PSQI), and the Beck Depression Inventory (BDI). RESULTS:
      91.30% of mothers reported poor sleep by PSQI standards. Regarding signs and
      symptoms of depression, 69.56% of all mothers in this sample showed them. Direct
      correlation between Sao Paulo mothers PSQI and BDI was found and also between the
      child's age and BDI. CONCLUSION: The mothers' poor sleep was related to mood
      changes with symptoms of depression presenting similar results in both cities.

PMID- 18813705
TI  - Correlation between migraine subtypes and depression.
AB  - This study has evaluated depression in patients with episodic migraine (n=98),
      chronic migraine without medication overuse (n=23), and chronic migraine with
      medication overuse (n=57). The Beck Depression Inventory (BDI) was used to
      evaluate depressive symptoms in these three groups. The mean BDI score obtained
      in all patients was higher than that observed in asymptomatic subjects (episodic
      migraine=16.09+/-11.79, chronic migraine with medication overuse=18.91+/-12.53,
      chronic migraine without medication overuse=19.83+/-14.79). This finding
      corroborates previous studies suggesting a co-morbid association between migraine
      and depression. Depression did not seem to be crucial in the transformation of
      migraine as the median BDI scores did not differ significantly between patients
      with episodic and chronic migraine. The median BDI scores of the patients with
      chronic migraine with medication overuse and that patients with chronic migraine
      without medication overuse were similar as well. Therefore, medication overuse
      behavior may not be related with depression.

PMID- 18813706
TI  - Handedness of children determines preferential facial and eye movements related
      to hemispheric specialization.
AB  - BACKGROUND: Despite repeated demonstrations of asymmetries in several brain
      functions, the biological bases of such asymmetries have remained obscure.
      OBJECTIVE: To investigate development of lateralized facial and eye movements
      evoked by hemispheric stimulation in right-handed and left-handed children.
      METHOD: Fifty children were tested according to handedness by means of four
      tests: I. Mono-syllabic non-sense words, II. Tri-syllabic sense words, III.
      Visual field occlusion by black wall, and presentation of geometric objects to
      both hands separately, IV. Left eye and the temporal half visual field of the
      right eye occlusion with special goggles, afterwards asking children to assemble
      a three-piece puzzle; same tasks were performed contra-laterally. RESULTS: Right
      handed children showed higher percentage of eye movements to right side when
      stimulated by tri-syllabic words, while left-handed children shown higher
      percentages of eyes movements to left side when stimulated by the same type of
      words. Left-handed children spent more time in recognizing non-sense mono
      syllabic words. Hand laterality correlated with tri-syllabic word recognition
      performance. Age contributed to laterality development in nearly all cases,
      except in second test. CONCLUSION: Eye and facial movements were found to be
      related to left- and right-hand preference and specialization for language
      development, as well as visual, haptic perception and recognition in an age
      dependent fashion in a complex process.

PMID- 18813707
TI  - Trigger factors in migraine patients.
AB  - BACKGROUND: Migraine is a chronic neurological disease with several trigger
      factors, including dietary, hormonal and environmental factors. PURPOSE: To
      analyse precipitating factors in a sample of migraine patients. METHOD: Two
      hundred consecutive migraine patients were interviewed about possible trigger
      factors for migraine attacks. RESULTS: Most patients showed at least one dietary
      trigger, fasting was the most frequent one, followed by alcohol and chocolate.
      Hormonal factors appeared in 53%, being the pre-menstrual period the most
      frequent trigger. Physical activities caused migraine in 13%, sexual activities
      in 2.5% and 64% reported emotional stress a trigger factor. 81% related some
      sleep problem as a trigger factor. Regarding environmental factors, smells were
      reported by 36.5%. CONCLUSION: Trigger factors are frequent in migraine patients,
      its avoidance may decrease headache frequency and also improve patients' quality
      of life.

PMID- 18813708
TI  - Beneficial effects of botulinum toxin type A in trigeminal neuralgia.
AB  - Botulinum toxin has been thoroughly studied as a potential tool in the treatment
      of several pain syndromes. Therefore, we assessed the clinical effects of
      botulinum toxin type A injections in 12 patients with otherwise unresponsive
      idiopathic trigeminal neuralgia. Patients were infiltrated with 20-50 units of
      botulinum toxin in trigger zones. Those who presented with mandibular involvement
      were also infiltrated in the masseter muscle. The patients were assessed on a
      weekly basis using the Visual Analogic Scale for pain. Ten of our patients
      reported a significant benefit from botulinum toxin injections, with reduction or
      even disappearance of pain, and remained pain free for as long as 60 days. Our
      findings suggest that botulinum toxin may represent a useful therapeutic tool in
      the management of patients with this entity.

PMID- 18813709
TI  - sICAM-1 intrathecal synthesis and release during the acute phase in children
      suffering from Coxsackie A9 and S. pneumoniae meningoencephalitis.
AB  - The intercellular adhesion molecule is a transmembrane glycoprotein belonging to
      the immunoglobulin superfamily. Serum and cerebrospinal fluid (CSF) soluble
      intercellular adhesion molecule 1 (sICAM-1) from normal control children as well
      as from children with Guillain-Barre syndrome (GBS), with Coxsackie A9 virus
      meningoencephalitis and with Streptococcus pneumoniae meningoencephalitis were
      studied. sICAM-1 was quantified using an immunoenzimatic assay and albumin using
      the immunodiffusion technique in both biological fluids. Increased sICAM-1 values
      in CSF in patients with GBS correspond to an increase of the albumin CSF/serum
      quotient. In contrast, in inflammatory diseases like S. pneumoniae and Coxsackie
      A9 virus meningoencephalitis an increased brain-derived fraction was observed. In
      particular cases these values are 60-65% and 70-75% respectively. The results
      indicate an additional synthesis of sICAM-1 in subarachnoidal space during
      central nervous system (CNS) inflammatory process. An important role of sICAM-1
      in the transmigration of different cell types into CSF during CNS inflammation in
      children with S. pneumoniae and Coxsackie A9 meningoencephalitis may be
      suggested.

PMID- 18813710
TI  - Acute bacterial meningitis caused by Streptococcus pneumoniae resistant to the
      antimicrobian agents and their serotypes.
AB  - The main objectives of this study are to evaluate the resistance rates of
      Streptococcus pneumonia to penicillin G, ceftriaxone and vancomycin in patients
      with meningitis; to analyze possible risk factors to the antimicrobian
      resistance; to describe the serotypes detected and to suggest an initial
      empirical treatment for meningitis. The sensitiveness and serotypes of all
      isolated S. pneumoniae of patients with acute bacterial meningitis received by
      the Parana State Central Laboratory from April 2001 to august 2002 have been
      evaluated. One hundred S. pneumoniae have been isolated, of which 15% were
      resistant to penicillin, 1% to cephalosporin and 0% to vancomycin. The serotypes
      most found were 14 (19%), 3 and 23F (10% each). When only the resistant serotypes
      were analyzed, the most prevalent was the 14 with 44%. The risk factors found in
      relation to the S. pneumoniae resistance were: age under one year old (p=0.01)
      and previous use of antibiotic (p=0.046). The resistance rates found, which were
      moderate to penicillin, low to cephalosporin and neutral to vancomycin, suggest
      the isolated use of a 3rd generation cephalosporin as an initial empirical
      therapy for the treatment of acute bacterial meningitis with a communitarian
      background.

PMID- 18813711
TI  - Alterations of the myenteric plexus of the ileum and the descending colon caused
      by Toxoplasma gondii (genotype III).
AB  - Alterations caused by a genotype III strain of Toxoplasma gondii were assessed
      with respect to the number and the morphometry of the myenteric neurons in the
      terminal ileum and the descending colon. Eighteen rats were divided into four
      groups: Acute Control Group (ACG, n=4); Acute Experimental Group (AEG, n=4);
      Chronic Control Group (CCG, n=5) and Chronic Experimental Group (CEG, n=5). NaCl
      solution was administered through gavage to the animals in the ACG and CCG.
      Toxoplasma gondii tachyzoites (10(4)) from a genotype III strain were orally
      administered to the AEG and CEG. Acute Groups were died after 24 hours, and the
      Chronic Groups after 30 days. Neuronal loss was not observed in both organs. The
      neurons atrophied in the terminal ileum as the opposite occurred with the neurons
      at the descending colon during the chronic phase of infection. In the terminal
      ileum, the neurons atrophied during the chronic phase of the infection as no
      alteration was found during the acute phase. For the descending colon, the
      neurons became hypertrophic during the chronic infection in opposition to the
      atrophy found during the acute phase.

PMID- 18813712
TI  - Norms for the mini-mental state examination: adjustment of the cut-off point in
      population-based studies (evidences from the Bambui health aging study).
AB  - OBJECTIVE: To estimate the prevalence of cognitive impairment in an elderly
      population-based cohort, using several Mini-Mental State Examination (MMSE) cut
      off points recommended by Brazilian authors and to examine the percentile
      distribution of MMSE scores in the study population. METHOD: A total of 1558
      subjects aged>60 years (89.4% of the total), living in the city of Bambui, MG,
      completed the MMSE and were included in the present study. RESULTS: The estimated
      prevalences of cognitive impairment varied from 13.2% to 27.0% depending on the
      cut-off point and agreement varied widely between them (kappa range: 0.38 to
      0.88). Cut-off point 13/14 corresponded to the 5th percentile and 21/22
      corresponded to the lower quartile of the MMSE score distribution. CONCLUSION: In
      the absence of comparable cut-off points, percentile distributions are more
      adequate for population-based studies of elderly with low schooling level.

PMID- 18813713
TI  - Primary filum terminale ependymoma: a series of 16 cases.
AB  - Filum terminale ependymomas are slow growing tumors of the cauda equina with a
      high incidence in young adults. Although a complete microsurgical resection can
      lead to a cure, recurrence is not uncommon. Sixteen cases of filum terminale
      ependymomas treated at the Instituto de Neurologia de Curitiba were analyzed.
      Eleven patients were females and 5 males, their age ranging from 7 to 84 years.
      Symptoms and signs included lumbar pain (31.25%), radicular pain (56.25%) and
      neurological deficits (12.5%). In three cases, patients had previously undergone
      surgery in other hospitals. All were tested through MRI and were operated on. Two
      underwent a laminoplasty and 14 a laminectomy. The last 8 patients of this series
      had neuro-physiological monitoring during surgery. In all patients a total
      microsurgical resection was achieved. Histologically, 2 cases were cellular
      ependymomas and 14 cases myxopapillary ependymomas. There was no recurrence
      during a 2 to 84 month follow-up period.

PMID- 18813714
TI  - Cortical stimulation of language fields under local anesthesia: optimizing
      removal of brain lesions adjacent to speech areas.
AB  - OBJECTIVE: The main objective when resecting benign brain lesions is to minimize
      risk of postoperative neurological deficits. We have assessed the safety and
      effectiveness of craniotomy under local anesthesia and monitored conscious
      sedation for the resection of lesions involving eloquent language cortex.
      METHODS: A retrospective review was performed on a consecutive series of 12
      patients who underwent craniotomy under local anesthesia between 2001 and 2004.
      All patients had lesions close to the speech cortex. All resection was verified
      by post-operative imaging. Six subjects were male and 6 female, and were aged
      between 14 and 52 years. RESULTS: Lesions comprised 7 tumour lesions, 3
      cavernomas and 1 dermoid cyst. Radiological gross total resection was achieved in
      66% of patients while remaining cases had greater than 80% resection. Only one
      patient had a post-operative permanent deficit, whilst another had a transient
      post-operative deficit. All patients with uncontrollable epilepsy had good
      outcomes after surgery. None of our cases subsequently needed to be put under
      general anesthesia. CONCLUSION: Awake craniotomy with brain mapping is a safe
      technique and the "gold standard" for resection of lesions involving language
      areas.

PMID- 18813715
TI  - Restless legs syndrome associated with cardiac failure and aggravated after
      valvular replacement: Vesper's curse?

PMID- 18813716
TI  - Primary central nervous system lymphoma in an immunocompetent host.

PMID- 18813717
TI  - Congenital disorder of glycosylation type Ia: a non-progressive encephalopathy
      associated with multisystemic involvement.

PMID- 18813718
TI  - Atypical presentation of vanishing white matter disease.

PMID- 18813719
TI  - Excessive water ingestion and repeated seizures: the domino effect.

PMID- 18813720
TI  - Extremely delayed cerebral vasospasm after subarachnoid hemorrhage.

PMID- 18813721
TI  - Cerebral revascularization in a case of ischemic cerebrovascular disease.

PMID- 18813722
TI  - Thrombosed developmental venous anomaly associated with cerebral venous infarct.

PMID- 18813723
TI  - Internal carotid artery blood blister-like aneurysm.

PMID- 18813724
TI  - A giant partially thrombosed AICA aneurysm.

PMID- 18813725
TI  - Primary hemangioma of the skull.

PMID- 18813726
TI  - Detection of intrathecal IgM, IgG and IgA in a Cuban West Nile virus confirmed
      case.

PMID- 18813727
TI  - Choreoathetosis secondary to lead toxicity.

PMID- 18813728
TI  - Cerebellar degeneration secondary to acute lithium carbonate intoxication.

PMID- 18813729
TI  - Stroke in ancient times: a reinterpretation of Psalms 137:5,6.
AB  - Stroke was probably first described in Psalms 136: 5-6 of the Catholic Bible, and
      Psalms 137:5-6 of the Evangelical Bible. Based on the Portuguese, Spanish,
      English, German, Dutch, Russian, Greek, and original Hebrew Bible, the
      significance of this Psalm is the invocation of a punishment, of which the final
      result would be a stroke of the left middle cerebral artery, causing motor
      aphasia and right hemiparesis.

PMID- 18813730
TI  - Professor Octavio de Silveira: the pioneer of neurology in the State of Parana.
AB  - The author gives a brief overview of the career of Professor Octavio da Silveira,
      the first neurologist and professor of neurology in the State of Parana, as well
      as the first full professor of clinical neurology in the Federal University of
      Parana.

PMID- 18813731
TI  - Professor Antonio Branco Lefevre: the forefather of child neurology in Brazil.
AB  - OBJECTIVE: To report on the life and works of Prof. Antonio Branco Lefevre and
      the relevance that led him to be considered the Forefather of Child Neurology in
      Brazil. METHOD: The method utilized was the historical documents research;
      bibliographical. RESULTS: Antonio Branco Lefevre (1916-1981) was born in Sao
      Paulo city; graduated in 1941 from the Sao Paulo Medical School. The date--1950-
      can be considered when Child Neurology took shape for a fully specialty, when
      Lefevre presented his two internationally acclaimed thesis. Lefevre was
      recognized as he founder of Child Neurology in Brazil since the early years of
      his brilliant academic activities. In 1967 achieved the title of professor in the
      Child Neurology Clinic. His numerous trainees and Residents--from -1950 to 1981-
      held today key positions in Brazilian Child Neurology. CONCLUSION: The extension
      and importance of the Child Neurology School of which he is the legitimate
      founder is recognized.

PMID- 18813732
TI  - Guidelines for drug treatment of epilepsy: a critical review.
AB  - This article critically reviews the role of evidence-based medicine and its
      guidelines, from their logistic preparation to their interpretation. The
      strengths and weaknesses of the methodological points are presented, as well the
      reasons for the extreme popularity of the guidelines in developed countries. The
      review discusses the main foundations of the most cited guidelines and some
      recent large studies. Some of the final conclusions are that clinical experience
      is always an important factor to consider, even in the face of solid evidence, to
      achieve the best possible management of any particular patient.

PMID- 18813735
TI  - Nymph and adult biology of Dichelops melacanthus (Dallas) (Heteroptera:
      Pentatomidae) feeding on cultivated and non-cultivated host plants.
AB  - The biology of the pentatomid Dichelops melacanthus (Dallas) feeding on
      cultivated and non-cultivated plants was studied in the laboratory. Nymph
      mortality varied from approximately 60 on corn (seed mature) to 77% on wheat (ear
      immature); no nymphs survived on seedlings of corn or wheat. Nymph developmental
      time on soybean, corn or wheat (seed, pod or ear) varied from 25.5 to 32.8 days.
      Body weight at adult emergence was similar and greater on most foods than on
      wheat ear. Nymphs fed preferentially on soybean (pod immature). On non-cultivated
      hosts, nymphs showed high mortality (73%) on crotalaria (pod immature); on
      tropical spiderwort (stem) all nymphs died. Nymphs took longer time to develop on
      crotalaria and/or on spiderwort than on soybean. Body weight at adult emergence
      did not differ on crotalaria or soybean. Survivorship decreased with time on most
      foods, with approximately 50% of adults alive at day 30. On corn and wheat
      seedlings approximately 80% of adults were dead on day 20. Adult longevity ranged
      31-43 days, except on corn and wheat seedlings < 15 days. Females % ovipositing
      peaked ( approximately 76%) on soybean (pod or seed immature), and was minimum (
      approximately 9%) on wheat ear (immature); no females reproduced on seedlings of
      corn or wheat. Preoviposition period was shorter ( approximately 12 days) on
      soybean (immature pod or seed) and longer ( approximately 37 days) on wheat (ear
      immature). Fecundity was similar and higher on all foods than on wheat (ear
      immature). Body weigh gain occurred on all foods, but on corn and wheat
      seedlings. Adults fed preferably on soybean (pod immature and seed mature); wheat
      (seedling) was the least preferred food.

PMID- 18813736
TI  - [Influence of nutritional substrates on the development of Diaphania hyalinata L.
      (Lepidoptera: Crambidae)].
AB  - The aim of this research was to evaluate the biological behaviour of melonworm at
      different natural and artificial diets. Squash cultivar jacare, cucumber, summer
      squash and an artificial diets developed by Hensley & Hammond for the sugarcane
      borer were tried. The research was carried out in the Laboratorio de Entomologia
      do Centro de Ciencias Agrarias of the Universidade Federal do Espirito Santo, in
      climatized room at 25 +/- 1 masculineC, relative humidity of 70 +/- 10% and 14h
      photofase. The caterpillars fed on each substrate during the whole life cycle.
      Differences in duration of the larval period, larvae and pupae survival, adult
      longevity and number of eggs were registered between the substrates. The results
      show that the best diet for rearing is the artificial one. Between the natural
      diets the cucumber showed the best results.

PMID- 18813737
TI  - Photoperiodism and seasonality in neotropical population of Plutella xylostella
      L. (Lepidoptera: Yponomeutidae).
AB  - Neotropical populations of the diamondback moth Plutella xylostella L. have
      seasonal cycles of growth and decrease, and moth migration plays a fundamental
      role in generating such population dynamics. Since the oscillation of these
      populations is predictable, photoperiod might operate as a signal that triggers
      the migratory behaviour of the insect. Migration in insects is usually preceded
      by reproductive diapause, a photoperiodic response that can be characterised by
      morphological, physiological and behavioural alterations that permit to
      discriminate between migratory and non-migratory forms. In this study, I tested
      whether the pre-imaginal and reproductive development of P. xylostella from Minas
      Gerais (Brazil) is affected by artificial day-lengths that are equivalent to the
      periods of natural population growth or decrease. No evidence of photoperiodic
      response was found for the insect reared in laboratory on five different constant
      photoperiods, from 8h to 16h of light per day. There was no significant variation
      in survival and duration of egg, larva, and pupa stages or in pupal weight, adult
      size (forewing length), fecundity, and longevity. Although some species have
      geographically distinct photoperiodic responses, previous assumptions that
      cosmopolitan P. xylostella responds to photoperiod in temperate regions was
      questioned. Migratory and population seasonality among neotropical populations of
      P. xylostella certainly occurs independently of the photoperiodic announcement of
      seasonal changes in habitat quality.

PMID- 18813738
TI  - A test of Allen's rule in ectotherms: the case of two south American Melanopline
      Grasshoppers (Orthoptera: Acrididae) with partially overlapping geographic
      ranges.
AB  - We studied the geographic variation of three morphometric characters in relation
      to body size in two South American grasshoppers (Acrididae), Dichroplus vittatus
      Bruner and D. pratensis Bruner to test Allen's rule in these ectotherms. Since
      both species follow the converse to Bergmann's rule owing to latitudinal and/or
      altitudinal variation in time available for growth and reproduction, geographic
      variation in body size proportions of protruding parts may obey to differential
      allometric growth in different geographic areas. Alternatively, it could reflect
      true Allenian variation related to thermoregulation. Body proportions were
      studied by correlation/regression analyses with geographic and climatic
      variables. In D. pratensis, body proportions increased with latitude and
      decreased with altitude. These results probably obey to the effects of water
      balance and seasonality on final body size, and on the allometric growth of the
      three studied characters not being related to thermoregulation. In D. vittatus, a
      generally non-significant trend towards the decrease of the mean proportions of
      all three characters with increasing latitude was observed. Nevertheless, also in
      this species, it is probable that the environmental gradient responds to
      seasonality factors (although not to water balance) that affect the length of
      growing season and, in consequence, body size and its allometric relationships.
      We conclude that the regularities in the geographic distribution of body
      proportions of D. pratensis and D. vittatus do not follow Allen's rule in the
      sense of thermoregulation, and result from variables that determine growing
      season length and the allometric growth of different body parts.

PMID- 18813739
TI  - What is the effect of soil use on ant communities?
AB  - Studies on ant communities in agroecosystems have contributed to the knowledge of
      the effect of agricultural activities on biological communities. The aim of this
      study is to explain the effect of soil use on ant communities. We tested the
      hypothesis that there was a decrease in ant species richness and a change in the
      species composition at habitats with more intense soil use. We collected ants
      using sardine baits, subterranean traps and direct sampling at four habitats with
      different soil use (secundary forest, Acacia forestry, initial stage of
      succession and mixed crops). The ant species richness did not decrease with
      intensity of soil use. In successional habitat the species numbers collected
      using sardine baits and subterranean traps were significantly different. Species
      composition of communities had a pronounced variation, with the epigaeic and
      hypogaeic ant faunas of the habitat with high intense soil use (mixed crops) had
      low similarity with ant communities of the three other habitats. The predator
      species were restricted to habitats with low intensity of soil use. Then, species
      composition could better reflect the functional changes on ant communities than
      species richness. Our data can help to choose the component of ant community that
      better reflect the response of biodiversity to agricultural impacts.

PMID- 18813740
TI  - [The use of floral resources by Visitors on Sparattosperma leucanthum (Vell.) K.
      Schum. (Bignoniaceae)].
AB  - Aiming to estimate the rate of exploitation of the floral resources of
      Sparattosperma leucanthum (Vell.) K. Schum. as well as the interaction with their
      floral visitors in the pollination, the number of visits by flower was sampled,
      according to the type of visitation, the collected resource and the visitor's
      behavior during the forage for flowers. The floral visitors were grouped into
      seven guilds, organized in decreasing order of benefit to the S. leucanthum
      flower's pollination: effective pollinator, occasional pollinator, endogamic
      pollinator, generalist visitor, thievery visitor, thievery-pillager ant and
      pillager visitor. The total of 48.2 +/- 8.84 visits were recorded by flower.
      Nearly 50% of the visits resulted in nectar thief or pillage, which posed some
      problems to the reproduction of S. leucanthum, such as the drop in the
      attractiveness to pollinators and the harm to the flower's reproductive tissues.
      Trigona spinipes (Fabr.) (Hymenoptera: Apidae) was considered the most harmful
      species owing to the high frequency of pillage and forage. Bombus sp1, however,
      was probably the species that pollinated S. lecanthum flowers the most, making
      use of the crossed pollination.

PMID- 18813741
TI  - Evaluation of three methods for sampling ground-dwelling Ants in the Brazilian
      Cerrado.
AB  - Few studies have evaluated the efficiency of methods for sampling ants,
      especially in regions with highly variable vegetation physiognomies such as the
      Cerrado region of central Brazil. Here we compared three methods to collect
      ground-dwelling ants: pitfall traps, sardine baits, and the Winkler litter
      extractor. Our aim was to determine which method would be most appropriate to
      characterize the ant assemblages inhabiting different vegetation types. More
      species were collected with pitfall traps and with the Winkler extractor than
      with sardine baits. Pitfall traps collected more species in the cerrado (savanna)
      physiognomies, particularly in those with a poor litter cover, whereas the
      Winlker extractor was more efficient in the forest physiognomies, except the one
      subject to periodic inundations. There was a low similarity in species
      composition between forest and cerrado physiognomies, and this pattern was
      detected regardless of the method used to sampling ants. Therefore, even the use
      of a single, relatively selective method of collection can be enough for studies
      comparing highly distinct habitats and/or conditions. However, if the purpose of
      the sampling is to produce a more thoroughly inventory of the ant fauna, we
      suggest the use of a combination of methods, particularly pitfall traps and the
      Winkler extractor. Therefore, the Ants of the Leaf-Litter (ALL) Sampling Protocol
      appear to be an adequate protocol for sampling ants in the highly-threatened
      Brazilian cerrado biome.

PMID- 18813742
TI  - Abundance and species richness of Coreoidea (Hemiptera: Heteroptera) from Parque
      Estadual do Turvo, Southern Brazil.
AB  - The coreoid fauna from Neotropics is poorly known, especially in terms of
      community studies. Aiming at contributing to this knowledge, a two-year study was
      carried out at Parque Estadual do Turvo, Municipality of Derrubadas, state of Rio
      Grande do Sul, Brazil, to evaluate the composition, abundance and species
      richness of Coreoidea. Samplings were conducted in the springs of 2003 and 2004
      (October), and autumns of 2004 and 2005 (May), using beating tray method, along
      two trails of the park. Sampling effort (hours X collectors) totaled 153h. A
      total of 282 individuals of Coreoidea were collected, distributed in 28 species
      of Alydidae, Coreidae and Rhopalidae. The most abundant species was the coreid
      Cebrenis supina Brailovsky, representing 16% of the collected individuals,
      followed by the rhopalids Jadera aeola (Dallas), and Harmostes sp., with 12.1%
      and 11.7%, respectively. The estimated richnesses by Chao 1, Chao 2, Jackknife 1
      and Jackknife 2 indicated that the observed richness corresponds to 70% to 80% of
      the expected for the area. The estimated richness through rarefaction was
      significantly higher in spring 2003 and autumn 2004 than in the other periods.
      There was no significant difference, however, between spring of 2003 and autumn
      of 2004, and between spring of 2004 and autumn of 2005, for the same parameter.
      Yucuma and Garcia trails did not differ significantly for the estimated richness.
      Singletons and doubletons represented 32.1% of the recorded species.
      Additionally, eight other species were obtained qualitatively by using, besides
      beating tray without protocol, manual collection.

PMID- 18813743
TI  - Morphological regional differences of epithelial cells along the midgut in
      Diatraea saccharalis Fabricius (Lepidoptera: Crambidae) larvae.
AB  - The sugarcane borer, Diatraea saccharalis Fabricius, is a pest to sugarcane and
      many other crops. This work aims to characterize morphological variability in the
      epithelial cells (columnar, goblet and regenerative) along the midgut of D.
      saccharalis larvae. Fragments of the midgut (anterior, middle and posterior
      regions) were fixed and processed by light and scanning electron microscopy.
      There are both cytochemical and ultrastructural differences in the morphology of
      the epithelial cells, depending on their localization along the midgut. The
      apical surface of columnar cells shows an increase in both number and size of the
      apical protrusions from the anterior to the posterior midgut regions. There is an
      increase in the amount of PAS-positive (Periodic Acid-Schiff Reaction) granules
      detected in the cytoplasm of both the columnar and regenerative cells, from the
      anterior to the posterior region. The goblet cell apical surface is narrow in the
      anterior region, and enlarged in the posterior midgut; the chamber's cytoplasm
      extrusion are small and thin at the apical cavity surface, being thicker, longer
      and more numerous at the basal portion of the cavity. Our results suggest that
      the sugarcane borer midgut has two morphologically different regions, the
      anterior and the posterior; the middle region is a transitional region.

PMID- 18813744
TI  - A new species of Laranda Walker 1869 (Orthoptera: Grylloidea, Phalangopsidae)
      from remnant patches of the Brazilian Atlantic Forest.
AB  - The genus Laranda has six described species and is confined to South and
      Southeast of Brazil. We describe a new species and discuss the biology and
      distribution of the genus. The new species can be distinguished from its known
      congeners by the following characteristics: absence of yellow spots on pronotum
      and base of posterior tibiae; female copulatory papilla: sclerotization in dorsal
      view forming opposing acute angles, apical lobes narrow and small; male
      genitalia: pseudepiphallic median process short and wide; pseudepiphallic
      paramere with apex incurved and ectophallic fold surpassing apex of the
      parameres. The genus is distributed within the Atlantic Forest biome; the new
      species is found on tree trunks, as well as on forest leaf litter.

PMID- 18813745
TI  - [Tabanidae (Diptera) of State of Maranhao, Brazil II. Description of Esenbeckia
      (Esenbeckia) rafaeli, sp. nov].
AB  - Esenbeckia (Esenbeckia) rafaeli, sp.nov. is described and figured from nine
      specimens collected in Carolina, state of Maranhao, Brazil. The new species is
      compared with the species Esenbeckia (Esenbeckia) laticlava Wilkerson &
      Fairchild, 1983; Esenbeckia (Esenbeckia) bitriangulata Lutz & Castro, 1935 e
      Esenbeckia (Esenbeckia) enderleini Krober, 1931.

PMID- 18813746
TI  - Morphology of male reproductive system in three species of Trypoxylon
      (Trypargilum) Richards (Hymenoptera: Crabronidae).
AB  - Variations in the adult male reproductive system among different groups of
      Hymenoptera offer characteristics that help studies on behavior and
      phylogenetics. The objective of this study was to describe the adult male
      reproductive system of three Trypoxylon (Trypargilum) species. For that, tissues
      were disseced, fixed in 2.5% glutaraldehyde in 0.1 M sodium cacodylate buffer, pH
      7.2 and postfixed in 1% osmium tetroxide. The material was dehydratated and
      embedded for light and electron transmission microscopes. The species have
      similar reproductive systems, which are formed by a pair of testes, each one with
      three fusiforme follicles, from which emerges an efferent duct that later joins
      forming a deferent duct. The deferent duct opens into an ejaculatory duct. The
      first half of the deferent duct is enlarged and differentiated in a region
      specialized in sperm storage, the seminal vesicle. The accessory gland flows in
      the post-vesicular region of the deferent duct. The testes and vesicles are both
      covered with a conjunctive capsule. Sexually mature individuals have all
      spermatogenesis stages in their follicles. Sperms are released from testes in
      bundles which are disorganized inside seminal vesicles.

PMID- 18813747
TI  - [Hemipteran diversity (Cicadellidae and Clastopteridae) in three coffee
      production zones affected by Xylella fastidiosa (Wells et al.) in Costa Rica].
AB  - A survey was conducted during 2002, 2003 and 2004 to determine the leafhopper
      species composition, abundance, richness, diversity, evenness, occurrence and
      flight activity among three coffee production zones of Costa Rica. Yellow sticky
      traps were used to qualify and quantify the number of aerial leafhoppers during
      the sampling period. A total of 82,500 individuals, belonging to 139 species
      within nine leafhopper subfamilies, were trapped. San Isidro de Leon Cortes site
      presented the highest diversity from the three surveyed sites. Twenty five
      species were frequently trapped at least in one of the studied zones, and only
      Coelidiana sp.1, Osbornellus sp.1, Scaphytopius sp.1 and Empoasca sp. were
      trapped throughout the sampling period. The flight activity of the taxa that
      contain the main vectors of Xylella fastidiosa Wells et al. showed differences
      among the sampling zones.

PMID- 18813748
TI  - Faunistic analysis of sharpshooters (Hemiptera: Auchenorrhyncha, Cicadellidae) in
      a 'Westin' sweet orange orchard.
AB  - The purpose of this study was to analyze sharpshooter fauna in a five-year-old
      'Westin' sweet orange orchard. Yellow sticky traps were placed on the edge of a
      forest, and on the periphery and inside the citrus stand. The traps were
      evaluated fortnightly, for three years. The most frequent species were Acrogonia
      citrina Marucci & Cavichioli, Bucephalogonia xanthophis (Berg), and Oncometopia
      facialis (Signoret). B. xanthophis occurred more in the forest edge, especially
      on spring and winter. A. citrina occurred most frequently in the forest edge,
      especially on spring. The highest incidence of O. facialis was inside the citrus
      stand, on spring and summer. Other cicadellids occurred more often in the forest
      edge, especially on summer. A. citrina, B. xanthophis, Dilobopterus costalimai
      Young, and O. facialis were predominant in all places studied. A. citrina, B.
      xanthophis and O. facialis were super dominant, super abundant, super frequent,
      and constant, except inside the stand, where B. xanthophis was dominant, very
      abundant, very frequent, and constant. D. costalimai and Homalodisca ignorata
      Melichar were dominant, very abundant, and very frequent in the forest edge and
      in the periphery of the stand, and D. costalimai was also predominant inside the
      stand. Scopogonalia subolivacea (Stal) was predominant in the forest edge and
      inside the stand, while Plesiommata corniculata Young was predominant in the
      periphery (both were dominant, very abundant, very frequent, and accessory).

PMID- 18813749
TI  - Population dynamics of Aceria guerreronis Keifer (Acari: Eriophyidae) and
      associated predators on coconut fruits in Northeastern Brazil.
AB  - Aceria guerreronis Keifer can cause severe damage to coconuts in several
      countries around the world. Rare studies have been conducted to determine the
      predatory mites associated with A. guerreronis in Brazil. The study evaluated the
      prevalence of A. guerreronis and associated predators on the bracts and on the
      surface of the fruits underneath the bracts, for 12 months, on coconut palms
      grown along the coast of the States of Alagoas, Paraiba and Pernambuco,
      Northeastern Brazil. Mites of 10 families were found, but by far the most
      abundant species was A. guerreronis, corresponding to 99.5% of the mites
      collected. The prevailing species amongst the predators were the Phytoseiidae
      mites Neoseiulus baraki (Athias-Henriot) and Neoseiulus paspalivorus (De Leon).
      These are flat mites that have short limbs, characteristics that allow them to
      invade the main habitat occupied by A. guerreronis. Other predators were found,
      but in low numbers, due mainly to their difficulty in reaching the fruit areas
      most inhabited by A. guerreronis. However, these mites could prey on that pest
      when it leaves its preferred habitat to disperse. No significant correlations
      were observed between the levels of abiotic factors and the population levels of
      A. guerreronis or of the phytoseiids associated with it. This probably occurred
      due to the simultaneous and conflicting effects of those factors on the mites in
      the field, or to significant differences between the climatic factors measured in
      the environment and those prevailing in the habitat occupied by A. guerreronis.

PMID- 18813750
TI  - [Mites (Acari) from rubber trees (Hevea brasiliensis Muell. Arg., Euphorbiaceae)
      and spontaneous euphorbiaceous in rubber trees cultivation].
AB  - Quarterly samples were done in 2001 on three rubber tree plantation in the
      northwest of the state of Sao Paulo. Three rubber trees of each locality were
      sampled. Between the rows of rubber tree four species of spontaneous
      euphorbiaceous were collected: Chamaesyce hirta, C. hyssopifolia, Euphorbia
      heterophylla and Phyllanthus tenellus. A total of 8.954 mites of 38 species,
      belonging to 31 genera of 11 families were collected. Tydeidae and Phytoseiidae
      had the highest diversity of species, 9 and 7, respectively. The most abundant
      families were Eriophyidae (3.594), Tydeidae (2.825) and Tenuipalpidae (1.027).
      The most abundant species on the rubber trees were: phytophagous - Calacarus
      heveae Feres, Tenuipalpus heveae Baker, Lorryia sp.2, Lorryia formosa Cooreman
      and Lorryia sp.1; predators - Zetzellia quasagistemas Hernandes & Feres,
      Pronematus sp., Iphiseiodes zuluagai Denmark & Muma and Euseius citrifolius
      Denmark & Muma. Among the spontaneous euphorbiaceous, predatory mites were
      abundantly found on C. hirta and E. heterophylla, mainly Pronematus sp. and E.
      citrifolius, suggesting that these plants could be important in the maintenance
      of these predators in the rubber tree cultivation areas. However, plants that can
      shelter predators and at the same time exert strong competition (nutrients, water
      etc) to rubber trees, can not be recommended for pest management programs.
      Studies about competition between rubber trees and spontaneous plants need to be
      conducted for feasible efficient programs of environmental management, aiming at
      the control of pest mites of rubber tree.

PMID- 18813751
TI  - [Ants in a hospital environment and its importance as vector of bacteria].
AB  - The external ant community of Hospital Municipal de Morrinhos, in Morrinhos,
      Goias State, was characterized by the low rates of richness, diversity, dominance
      and equity of species abundance. Pheidole sp.1, a polygynic species was
      numerically dominant in this environment, although it coexists with potentially
      competitive species. This ant species prevailed within all hospital departments
      and its space-time distribution was a little aggregated (variance/mean ratio =
      1.102, chi2 = 29.38, P < 0.01). Escherichia, Salmonella, Aeromonas, Enterococcus,
      Staphylococcus and Klebsiella were the bacteria associated to this ant species in
      nearly all hospital annexes. The unicolonialism of Pheidole sp.1 tends to
      increase the contamination and dissemination process of infecto-contagious
      agents. The control and management of this ant species must be followed by
      practices that reduce the colonization process by other queens and the quantity
      of site nidification within the hospital.

PMID- 18813752
TI  - Calibration and evaluation of field cage for oviposition study with Aedes
      (Stegomyia) aegypti female (L.) (Diptera: Culicidae).
AB  - Differences among results gathered from insect behavior studies conducted in
      laboratory and field situations are due to ambient variables that differ greatly
      between both environments. In laboratory studies the environmental conditions can
      be controlled whereas in field temperature, humidity and air velocity vary
      uncontrollably. The objective of this study was to calibrate and evaluate an
      experimental area (field cage) (14 x 7 x 3.5 m) subdivided into eight test cages
      (2.5 x 2.5 x 2 m) for use in behavioral oviposition tests of Aedes aegypti (L.)
      mosquitoes for developing a new methodology to assess attractants and oviposition
      traps. Test cage calibration involved: (1) minimal experiment duration tests; (2)
      optimal female release number per traps test and (3) trap placement tests. All
      tests used gravid A. aegypti females; 3-4 days post blood meal and the sticky
      trap MosquiTRAP to catch adults. Ninety percent of the females released were
      recaptured 2h after the beginning of the experiment, and this allowed up to 32
      test repetitions/day to be conducted in the field cage. The minimum number of
      females necessary to conduct statistical analyses was 20 females/trap/test per
      cage. No significant difference was found in the behavioral response of gravid
      females to four different trap positions within test cages. Field trapping
      results with attractant were similar to those in the field cage. Therefore, the
      field cage could replace field trapping for evaluating at least mosquito traps
      and oviposition attractants for A. aegypti.

PMID- 18813753
TI  - Thrips (Thysanoptera: Thripidae, Phlaeothripidae) damaging peach in Paranapanema,
      Sao Paulo State, Brazil.
AB  - Seeking to identify thrips species associated to peach and the injuries they
      cause, plants of Aurora and Tropic Beauty cultivars were weekly monitored, from
      May to August of 2005, in Holambra II district, in Paranapanema, SP. Flowers and
      fruits from six plants per hectare were sampled by the hitting technique.
      Frankliniella occidentalis (Pergande), F. schultzei (Trybom), F. gardenia
      (Moulton), F. condei John, F. insularis (Franklin) and Thrips tabaci Lindeman, in
      Thripidae, and Haplothrips gowdeyi (Franklin), in Phlaeothripidae were
      identified. F. occidentalis was dominant, comprising 55.7% of the total specimens
      sampled. Slight and severe injuries were registered in fruits.

PMID- 18813755
TI  - Molecular characterization of vancomycin-resistant Enterococci strains eight
      years apart from its first isolation in Sao Paulo, Brazil.
AB  - E. faecium was the first reported VRE species, carrying the vanA gene in Brazil.
      In spite of this, vancomycin-resistant E. faecalis has become the predominant
      species in Brazilian hospitals. The aim of this study was to evaluate the genetic
      relatedness of VREs isolated in a Brazilian teaching hospital eight years apart
      from its first isolation. We analyzed 38 VRE strains obtained from 81
      surveillance cultures of patients admitted to the four largest intensive care
      units in Hospital Sao Paulo in February, 2006. Presence of the vanA gene was
      assayed by PCR and PFGE analysis was used for molecular characterization. All VRE
      strains carried the vanA gene. Two distinct clonal groups were observed among
      vancomycin-resistant E. faecalis. Vancomycin-resistant E. faecium belonged to
      five distinct clones were demonstrated by molecular typing. All of these clones
      were different from the first vancomycin-resistant enterococci clone isolated
      eight years ago in our hospital.

PMID- 18813756
TI  - Enzymatic characterization of Vibrio alginolyticus strains isolated from bivalves
      harvested at Venice Lagoon (Italy) and Guanabara Bay (Brazil).
AB  - The aquatic ecosystem is the natural habitat of microorganisms including Vibrio
      and Aeromonas genus which are pathogenic to human and animals. In the present
      investigation the frequency of these bacteria and the enzymatic characteristics
      of 34 Vibrio alginolyticus strains isolated from bivalves harvested in Venice
      Lagoon (Italy) and Guanabara Bay (Brazil) were carried out from November 2003 to
      February 2004. The mussels' samples were submitted to enrichment in Alkaline
      Peptone Water (APW) added with 1% of sodium chloride (NaCl) and APW plus 3% NaCl
      incubated at 37 degrees C for 18-24 h. Following the samples were streaked onto
      TCBS Agar (Thiossulfate Citrate Bile Sucrose Agar) and the suspected colonies
      were submitted to biochemical characterization. Also, the Vibrio alginolyticus
      strains were evaluated to collagenase, elastase and chondroitinase production.
      The results showed the isolation of 127 microorganisms distributed as follows:
      105 Vibrio strains such as V. alginolyticus (32.4%), V. harveyi (19%) and V.
      parahaemolyticus (7.6%), 20 Aeromonas strains and two Plesiomonas shigelloides
      were the main pathogens isolated. We observed the production of the three enzymes
      from V. alginolyticus strains considered as the main virulence factors of the
      bacteria, especially in cases of human dermatological infection.

PMID- 18813757
TI  - Cell surface hydrophobicity and adherence of a strain of group B streptococci
      during the post-antibiotic effect of penicillin.
AB  - The minimum inhibitory concentration and post-antibiotic effects of an
      antimicrobial agent are parameters to be taken into consideration when
      determining its dosage schedules. The in vitro post-antibiotic effects on cell
      surface hydrophobicity and bacterial adherence were examined in one strain of
      group B streptococci. Exposure of the microorganism for 2 h at 37 degrees C to 1
      x MIC of penicillin induced a PAE of 1.1 h. The cell surface charge of the
      Streptococcus was altered significantly during the post-antibiotic phase as shown
      by its ability to bind to xylene: hydrophobicity was decreased. Bacterial
      adherence to human buccal epithelial cells was also reduced. The results of the
      present investigation indicate that studies designed to determine therapeutic
      regimens should evaluate the clinical significance of aspects of bacterial
      physiology during the post-antibiotic period.

PMID- 18813759
TI  - Aids-related progressive multifocal leukoencephalopathy: a retrospective study in
      a referral center in Sao Paulo, Brazil.
AB  - Few data are available about progressive multifocal leukoencephalopathy (PML) in
      patients with acquired immunodeficiency syndrome (AIDS) from Brazil. The
      objectives of this study were to describe the main features of patients with PML
      and estimate its frequency among AIDS patients with central nervous system (CNS)
      opportunistic diseases admitted to the Instituto de Infectologia Emilio Ribas,
      Sao Paulo, Brazil, from April 2003 to April 2004. A retrospective and descriptive
      study was performed. Twelve (6%) cases of PML were identified among 219 patients
      with neurological diseases. The median age of patients with PML was 36 years and
      nine (75%) were men. Nine (75%) patients were not on antiretroviral therapy at
      admission. The most common clinical manifestations were: focal weakness (75%),
      speech disturbances (58%), visual disturbances (42%), cognitive dysfunction
      (42%), and impaired coordination (42%). The median CD4+ T-cell count was 45
      cells/microL. Eight (67%) of 12 patients were laboratory-confirmed with PML and
      four (33%) were possible cases. Eleven (92%) presented classic PML and only one
      case had immune reconstitution inflammatory syndrome (IRIS)-related PML. In four
      (33%) patients, PML was the first AIDS-defining illness. During hospitalization,
      three patients (25%) died as a result of nosocomial pneumonia and nine (75%) were
      discharged to home. Cases of PML were only exceeded by cases of cerebral
      toxoplasmosis, cryptococcal meningoencephalitis, and CNS tuberculosis, the three
      more frequent neurologic opportunistic infections in Brazil. The results of this
      study suggest that PML is not an uncommon HIV-related neurologic disorder in a
      referral center in Brazil.

PMID- 18813760
TI  - Clinical and histological characteristics of HIV and hepatitis C virus-co
      infected patients in Brazil: a case series study.
AB  - Hepatitis C virus (HCV) is an important factor contributing to morbidity and
      mortality in patients co-infected with HIV and HCV. In addition, liver biopsy is
      an important tool in the clinical management of these patients. Although liver
      biopsy is controversial, it is recommended for all patients. Data regarding the
      clinical and histological characteristics of these patients are scarce not only
      in Brazil but in Latin America as a whole. With the goal of better understanding
      these characteristics and the benefit of liver biopsy indications in this disease
      setting, data collected from 234 patients followed from 1996 to 2004 at Casa da
      AIDS, Sao Paulo, were analyzed. The following variables were extracted from the
      patients' medical files at the time of liver biopsy: sex, age, hepatitis C
      infection risk factors, hepatitis C infection duration, ALT levels, CD4+ T cell
      counts, history of alcohol abuse, history of antiretroviral therapy, HCV
      genotype, and liver histological alterations. CONCLUSIONS: 1 - Hepatitis C virus
      1 and 3 were the most frequently identified genotypes and were diagnosed in 72%
      and 25.5% of cases respectively; 2 - Structural liver alterations were found to
      be mild or absent in 48.2% (113/234) of the analyzed patients; 3 - Fifty-three
      patients (23%) had normal ALT levels and 4 - Significant liver architectural
      changes (F2-F3) were evident in 22.5% of the patients with normal ALT levels.

PMID- 18813761
TI  - High prevalence of hepatitis B virus among female sex workers in Nigeria.
AB  - Hepatitis B virus (HBV) infection is endemic in Nigeria and constitutes a public
      health menace. The prevalence of HBV infection in many professional groups has
      been described in Nigeria. However, literature on HBV infection among female sex
      workers (FSW) in Nigeria is scanty. FSW in Nigeria are not subjected to a
      preventive control of HBV infection. This study assesses the extent of spread of
      HBV among FSW in Nigeria. Seven hundred and twenty (n = 720) FSW (mean age = 26.7
      years) were tested for hepatitis B surface antigen (HBsAg) by a double antibody
      sandwich ELISA method. The overall HBV prevalence among the FSW was 17.1%. FSWs
      between the ages of 31-35 year (20.5%) and those with 'age-at-first-sex' below 10
      years of age (28%) were most affected. This high prevalence of a vaccine
      preventable disease is unacceptable, therefore, vaccination of this high risk HBV
      reservoir group should be considered worthwhile.

PMID- 18813762
TI  - Alterations in lipid transfer to high-density lipoprotein (HDL) and activity of
      paraoxonase-1 in HIV+ patients.
AB  - HIV+ patients often develop alterations of the plasma lipids that may implicate
      in development of premature coronary artery disease. High-density lipoprotein
      (HDL) has an important role in preventing atherogenesis and the aim of this study
      was to investigate aspects of HDL function in HIV+ patients. HIV+ patients (n =
      48) and healthy control subjects (n = 45) of both sexes with similar age were
      studied. Twenty-five were not being treated with antiretroviral agents, 13 were
      under reverse transcriptase inhibitor nucleosidic and non-nucleosidic
      (NRTI+NNRTI) and 10 were under NRTI + protease inhibitors (NRTI+PI) treatment.
      Paraoxonase 1 (PON1) activity and the transfer of free and esterified
      cholesterol, tryglicerides and phospholipids from a lipidic nanoemulsion to HDL
      were analyzed. In comparison with healthy controls, HIV+ patients presented low
      PON-1 activity and diminished transfer of free cholesterol and tryglicerides. In
      contrast, phospholipid transfer was increased in those patients, whereas the
      transfer of cholesteryl esters was unchanged. NRTI+NNRTI increases the transfer
      of cholesteryl esters and triglycerides but in NRTI+PI there was no difference in
      respect to non-treated HIV+ patients. HDL from HIV+ patients has smaller
      antioxidant properties, as shown by lower PON-1 activity, and the transfer of
      lipids to this lipoprotein fraction is also altered, suggesting that HDL function
      is defective in those patients.

PMID- 18813763
TI  - Biological implications of the phenotypic plasticity in the Schistosoma mansoni
      Nectomys squamipes model.
AB  - The water-rat Nectomys squamipes is mostly important non-human host in
      schistosomiasis mansoni transmission in Brazil, due to its susceptibility, high
      abundance and water-contact pattern. During experimental infection of N.
      squamipes with Schistosoma mansoni, adult worms show phenotypic plasticity. This
      finding led us to investigate whether biological behavior is also affected. This
      was assessed comparing the biological characteristics of four S. mansoni strains:
      BE (State of Belem do Para), CE (State of Pernambuco), CMO (State of Rio Grande
      do Norte) and SJ (State of Sao Paulo) using laboratory-bred N. squamipes. The
      infection was monitored by determination of the pre-patent period, fecal egg
      output, egg viability, intestinal egg count and, infectivity rate. No biological
      modification was observed in these parameters. Overall results highlight that N.
      squamipes was susceptible to several S. mansoni strains, suggesting that it might
      contribute to the maintenance of schistosomiasis mansoni in Brazil.

PMID- 18813764
TI  - Dot-Elisa for evaluation of hydatid cyst wall, protoscoleces and hydatid cyst
      fluid antigens in the serodiagnosis of cystic echinococcosis.
AB  - The aim of the present study is to evaluate cyst wall and protoscolex as an
      alternate source of antigen in serodiagnosis of cystic echinococcosis (CE). A
      total of 90 blood samples, 30 each of confirmed CE cases, disease controls and
      healthy controls were collected. Dot-ELISA using cyst wall, protoscolex and cyst
      fluid were used to demonstrate anti-hydatid antibodies. The sensitivity of Dot
      ELISA using cyst wall, protoscolex and cyst fluid was 96.66%, 86.66% and 93.33%
      respectively and the specificity of the assay was 70% for Dot-ELISA using cyst
      fluid, protoscolex and cyst wall antigens. Results of the present study show that
      cyst wall and protoscolex can also be an useful source of antigen in detection of
      hydatid antibodies in the serodiagnosis of CE.

PMID- 18813765
TI  - Correlation between specific IgM levels and percentage IgG-class antibody avidity
      to Toxoplasma gondii.
AB  - Toxoplasmosis is an usually asymptomatic worldwide disseminated infection. In its
      congenital presentation it may lead to abortion or fetal malformations. Antenatal
      evaluation is considered of paramount importance to identify seronegative women
      and allow for prophylaxis. Recent improvements in sensitivity of IgM tests has
      made IgM detection an extremely protracted acute phase marker, and IgG avidity
      evaluation test became necessary. Observation has shown that a correlation can be
      established between IgM levels and avidity percentages, suggesting that
      frequently the avidity test may not be necessary. In this study we analyzed
      Toxoplasma gondii IgM levels of 202 samples and their IgG avidity percentages, in
      order to define specific levels whose IgM quantification could by itself define
      serodiagnosis and therefore make the avidity evaluation unnecessary. We showed
      that for IgM levels below 2.0 and above 6.0 serodiagnosis of toxoplasmosis could
      be established without need of IgG avidity test. IgM levels between these two
      parameters are associated with varying avidity indexes highlighting the
      importance of its evaluation as a means to confirm toxoplasmosis. Following this
      demonstration it was possible to avoid the avidity test for 75% of the cases, to
      reduce the turnaround time and to reduce costs.

PMID- 18813766
TI  - Astrocytic and microglial response and histopathological changes in the brain of
      horses with experimental chronic Trypanosoma evansi infection.
AB  - This study aimed to characterize astrocytic and microglial response in the
      central nervous system (CNS) of equines experimentally infected with T. evansi.
      The experimental group comprised males and females with various degrees of
      crossbreeding, ages between four and seven years. The animals were inoculated
      intravenously with 10(6) trypomastigotes of T. evansi originally isolated from a
      naturally infected dog. All equines inoculated with T. evansi were observed until
      they presented symptoms of CNS disturbance, characterized by motor incoordination
      of the pelvic limbs, which occurred 67 days after inoculation (DAI) and 124 DAI.
      The animals in the control group did not present any clinical symptom and were
      observed up to the 125th DAI. For this purpose the HE histochemical stain and the
      avidin biotin peroxidase method was used. Lesions in the CNS of experimentally
      infected horses were those of a wide spread non suppurative
      meningoencephalomyelitis.The severity of lesions varied in different parts of the
      nervous system, reflecting an irregular distribution of inflammatory vascular
      changes. The infiltration of mononuclear cells was associated with anisomorphic
      gliosis and reactive microglia was identified. The intensity of the astrocytic
      response in the CNS of the equines infected by T. evansi characterizes the
      importance of the performance of these cells in this trypanosomiasis. The
      characteristic gliosis observed in the animals in this experiment suggests the
      ability of these cells as mediators of immune response. The parasite, T. evansi,
      was not identified in the nervous tissues.

PMID- 18813767
TI  - L. (L.) chagasi in AIDS and visceral leishmaniasis (kala-azar) co-infection.
AB  - Concomitant skin lesions in visceral leishmaniasis (VL) or kala-azar are rare,
      being more common the description of post-kala-azar dermal leishmaniasis
      occurring post treatment of kala-azar. Skin lesions caused by Leishmania donovani
      are frequently seen in the aids-VL co-infection. In Brazil cutaneous or mucosal
      forms of tegumentary leishmaniasis concomitant with aids are more commonly
      registered. Here we present a case of aids-VL co-infection, with unusual
      cutaneous and digestive compromising attributed to L. (L.) chagasi, with special
      attention to ecthymatous aspect of the lesion, allied to the absence of parasite
      on the histological skin biopsy.

PMID- 18813768
TI  - Recent developments in overall alcohol consumption and high risk drinking: a case
      for effective population level interventions in Canada.
AB  - There is growing evidence of extensive damage from alcohol to chronic disease,
      trauma, social problems and high economic costs. In a number of countries there
      has been an increase in consumption and/or high risk drinking in recent years.
      However, it appears that in many context alcohol management is not yet of high
      priority. Canada has experienced several developments in recent years: a gradual
      increase in overall consumption, an increase in high risk drinking, more
      extensive marketing and promotion of alcoholic beverages, and easier access to
      alcohol. Survey data for Canada, and for Ontario, the most populous province,
      indicate that the proportion drinking 5+ per occasion has increased since the mid
      1990s. Overall, alcohol-related harm has been conservatively estimated to
      contribute to $14 billion to social costs using 2002 Canadian data. There are a
      national and several provincial-level alcohol strategies designed to reducing
      alcohol-related problems, but they are at the proposal, not full-scale
      implementation, stage. In order to generate effective, efficient and decisive
      action and reduce overall harm, several recommendations are highlighted: an
      increase in alcohol pricing/taxation, a ceiling on further access via controls on
      outlet density and hours of sale, a rejuvenation of the control functions of
      liquor boards, and the resources to effectively implementation these measures.

PMID- 18813769
TI  - Is alcohol really good for health?
AB  - Several observational follow-up studies about cardiovascular health have found an
      overlap between moderate drinking and lower mortality from coronary heart disease
      and other causes. However, such studies have serious methodological limitations.
      Most non-drinkers were in fact ex-drinkers, that is, people who had had to stop
      drinking for health reasons. Other variables that may play a decisive role in
      cardiovascular risk, such as tobacco smoking, exercise and body mass index, were
      not evaluated, and changes in drinking habits were not assessed periodically. Due
      to the methodological limitations of these studies, the findings suggest a
      statistical association but not a causality relationship between moderate alcohol
      consumption and lower risk of mortality. Furthermore, numerous studies have shown
      that excessive drinking can cause not only cardiovascular diseases--such as
      hypertension, arrhythmias, dilated cardiomyopathy and stroke--but also other
      medical and psychiatric disorders. Alcohol clearly has addictive properties that
      can contribute to the development of heavy drinking in some people, leading to
      alcohol-related physical and mental disorders. The public health message should
      emphasize the potential risk of heavy drinking rather than promote the possible
      benefits of moderate consumption. A simplistic message that alcohol is good for
      cardiovascular health may be prejudicial when stated outside the context of the
      possible adverse consequences of heavy drinking.

PMID- 18813770
TI  - [Alcoholic and cocaine-dependent women: a comparative study from a qualitative
      perspective].
AB  - OBJECTIVE: To analyze social behaviours of alcoholic and cocaine-dependent women.
      METHOD: Six alcoholic women and six cocaine-dependent women in outpatient
      treatment made up the study sample. The technique used was that of life history
      interview. Data analysis was carried out based on Grounded Theory. RESULTS:
      Alcoholic women become dependent through progressive consumption, while cocaine
      dependent women begin cocaine use as consequence of a particular event or
      incident; cocaine use among these women is also related to pleasure-seeking and
      to drug-dependent partners. There is a social stigma in drug-dependent women-
      more evident in alcoholics--related to non-fulfillment of tasks and roles that
      society imposes on women. The illness concept also appears more often in the
      discourse of alcoholic women than in that of cocaine addicts. As regards the
      family, it has a double meaning for these women: on the one hand, it is the first
      context to suffer the consequences of their drug abuse, through lies, petty theft
      and verbal aggression; on the other, the family is an important source of support
      in the initiation and process of treatment. CONCLUSIONS: Drug abuse has specific
      social repercussions that should be taken into account in the establishment of
      appropriate help mechanisms.

PMID- 18813771
TI  - [High-dose methadone detoxification in a hospital unit. Clinical experience].
AB  - The increase in opiate addicts in treatment with methadone, coupled with improved
      survival of HIV patients, has meant an increase in the demand for detoxification
      from this substance in our environment. It is common practice in hospital
      detoxification units to request a maximum dose of methadone (around 40 mg) on
      beginning detoxification treatment. However this is not always possible, due to
      the time needed for a gradual decrease for outpatients making daily visits to the
      methadone dispensing centres, due to the appearance of withdrawal symptoms, or
      because the patient starts out from very high doses of methadone. Reported here
      is an experience with 22 inpatients who over the last two years underwent
      detoxification from methadone without requesting from their treatment centres a
      maximum-limit dose at the start of their treatment. During the detoxification
      they are given treatment with clonidine and benzodiazepines (dosage being
      adjusted according to concomitant use of alcohol, benzodiazepines and cocaine)
      and non-opiate-based painkillers. On the seventh day they are given 50 mg of
      naltrexone. Of these addicts, 21 completed the detoxification adequately.

PMID- 18813772
TI  - [Efficacy of oxcarbazepine treatment in patients diagnosed with cocaine
      abuse/dependence].
AB  - To assess the efficacy of oxcarbazepine in the treatment of cocaine addiction and
      its influence on impulsivity and craving in cocaine addicts. METHODOLOGY: A
      prospective, observational and clinical study was conducted in patients diagnosed
      with cocaine abuse/dependence (DSM IV criteria), monitoring supervised treatment
      with oxcarbazepine for 12 weeks. SAMPLE: 30 patients (aged 18 or over)
      voluntarily undergoing treatment at an Addictive Behaviors Unit (UCA). Patients
      were selected randomly after providing explicit authorization and informed
      consent. RESULTS: Abstinence rate increased, reaching 100% of participants that
      remained in compliance throughout the 12-week period (60% of those who started
      the treatment). Negative results in the urine test for cocaine detection also
      increased, reaching 90.9% of those in treatment at week 8. Treatment with
      oxcarbazepine was seen to produce a statistically significant reduction in
      craving and impulsivity after 4, 8 and 12 weeks, with respect to baseline
      measures at the start of treatment. The craving index correlates with reduction
      in cocaine use. CONCLUSIONS: Oxcarbazepine is effective in reducing impulsivity
      and craving in relation to cocaine. Thus, we recommend high initial doses of
      oxcarbazepine in patients with high impulsivity prior to treatment.

PMID- 18813773
TI  - [Prefrontal activity and weekend alcoholism in the young].
AB  - BACKGROUND: High alcohol consumption by young people at weekends is a public
      health problem of considerable social and family importance. Chronic alcohol
      intake causes structural changes in the central nervous system, though the
      effects are not uniform throughout the brain. The prefrontal cortex (PC) has been
      reported to be one of the regions most sensitive to prolonged alcohol ingestion.
      OBJECTIVES: The effects of chronic ethanol exposure have been extensively
      studied. Our aim is to identify the neuropsychological deficits in PC function
      induced by intermittent heavy alcohol drinking in young adults. METHODS:
      Neuropsychological assessment was carried out on participants to examine their
      performance in PC-dependent tasks. 62 subjects (mean age 18.82+/-1.099) were
      assigned to one of three categories: 1) Those reporting heavy binge drinking of
      alcohol at weekends (ALE); 2) Those reporting moderate binge drinking of alcohol
      at weekends (ALM); and 3) Those reporting no alcohol intake (CTR). RESULTS AND
      CONCLUSIONS: The findings indicate that intermittent alcohol binge drinking,
      either heavy or moderate, in young people results in poorer performance in
      neuropsychological tasks such as Digits, Corsi or Stroop, which depend on correct
      PC functioning. Our results support the claim that the binge pattern of exposure
      to ethanol leads to neurocognitive and neurobehavioural impairment equivalent, in
      many respects, to that found in chronic drinkers. Moreover, intermittent heavy
      alcohol drinking in adolescence and early adulthood increases the risks of
      lifetime alcohol dependence and other psychopathologies.

PMID- 18813774
TI  - [Injection Drug User Quality of Life scale (IDUQoL): psychometric assessment of
      the Spanish version].
AB  - BACKGROUND: The assessment of quality of life has become one of the priority
      indicators of outcomes in the field of clinical research. Therefore, it is
      necessary to use instruments adapted to and validated for the context in which
      they are to be used. PURPOSE: To assess the psychometric properties of the IDUQoL
      (Injection Drug User Quality of Life Scale) in its Spanish adaptation. METHOD:
      Participants were 100 persons with a diagnosis of opiate addiction who were on a
      methadone maintenance programme. They responded to the IDUQoL -in its 21-domain
      version- and two other quality of life instruments (the SF-36 and the EQ-5D).
      RESULTS: Good reliability data are obtained (Cronbach's alpha of 0.92 and
      Intraclass Correlation Coefficient for the test-retest of 0.79). Exploratory and
      confirmatory factor analyses and semi-partial correlations analysis confirm the
      unidimensionality of the construct, with explained variance of 43.8% and adequate
      fit indices (GFI = 0.92; CFI = 0.97; RMSEA = 0.044). Convergent and criterion
      related validity were also quite adequate (correlation coefficients with the SF
      36 and EQ-5D were situated between 0.34 and 0.61, and with other criterion
      variables between 0.23 and 0.39; p <0.05), even though the discriminant validity
      analysis is not completely conclusive. CONCLUSION: The findings from this study
      provide evidence to support the use of the IDUQoL as a specific quality of life
      instrument in the addictive disorders context, and confirm its appropriate
      characteristics in the Spanish adaptation.

PMID- 18813775
TI  - [Preliminary study on detox in outpatient care units with 18 alcoholic patients
      in Directly Observed Treatment].
AB  - Directly Observed Treatment (TOD-DOT) has been tested in different conditions.
      The objective of this work is to check whether a UCA-CAB (Centre for Addictive
      Behaviour) can achieve detox and reduce the risk of early relapse (up to 12
      weeks) in alcoholic patients. All patients had an established organic addiction
      and serious withdrawal syndrome, and had undergone multiple previous treatments.
      Furthermore, they had not managed to abstain for a 3-month consecutive period
      over the previous 2 years. The aim of the Directly Observed Treatment was to
      attain detox and reduce relapse by following a multi-method approach: medical,
      psychological and personal care, based on a brief daily consultation and
      pharmacological supervision. The results were as follows: Of the 18 patients
      included in the study, after 12 weeks, 13 (72 %) were still abstinent and 4 (22
      %) had relapsed. Thus, 17 (94 %) were still following the treatment, with just
      one drop-out. We analysed the profiles of the patients abstaining, of those who
      relapsed (4) and of the one who dropped out. The average CIWA-Ar was 27.05 (21
      36). Any value over 20 is considered to indicate serious withdrawal syndrome,
      though there were no negative events leading to hospitalization. Level of
      adherence to the treatment (94 %) meant that the most seriously affected patients
      and those with fewest financial resources could benefit, not only from any
      auxiliary social schemes, but also from basic health services, permitting them to
      improve the quality of their everyday life.

PMID- 18813776
TI  - Histone deacetylase inhibitors: apoptotic effects and clinical implications
      (Review).
AB  - It has been shown that epigenetic modifications play an important role in
      tumorigenesis. Thus, affecting epigenetic tumorigenic alterations can represent a
      promising strategy for anticancer targeted therapy. Among the key chromatin
      modifying enzymes which influence gene expression, histone acetyltransferases
      (HATs) and histone deacetylases (HDACs) have recently attracted interest because
      of their impact on tumor development and progression. Increased expression of
      HDACs and disrupted activities of HATs have been found in several tumor types,
      with a consequent hypoacetylated state of chromatin that can be strictly
      correlated with low expression of either tumor suppressor or pro-apoptotic genes.
      Histone deacetylase inhibitors (HDACIs) represent a new and promising class of
      antitumor drugs that influence gene expression by enhancing acetylation of
      histones in specific chromatin domains. HDACIs have been shown to exert potent
      anticancer activities inducing cell cycle arrest and apoptosis. Notably, a high
      efficacy of these drugs has been selectively revealed in malignant cells rather
      than in normal cells. Moreover, the therapeutic potential of these agents is also
      supported by the evidence that HDACIs downregulate genes involved in tumor
      progression, invasion and angiogenesis. Several HDACIs are currently under
      clinical investigation, including vorinostat (SAHA), romidepsin (depsipeptide, FK
      228), LAQ824/LBH589 and belinostat (PXD101), compounds that have shown
      therapeutic potential in many types of malignancies including solid tumors. Based
      on the ability of HDACIs to regulate many signaling pathways, co-treatment of
      these compounds with molecular targeted drugs is a promising strategy against
      many types of tumors.

PMID- 18813777
TI  - Growth inhibitory effects of pegylated IFN-alpha2b and 5-fluorouracil in
      combination on renal cell carcinoma cell lines in vitro and in vivo.
AB  - We investigated the effects of pegylated IFN-alpha2b (PEG-IFN-alpha2b) alone and
      PEG-IFN-alpha2b plus 5-fluorouracil (5-FU) in vitro on the proliferation of renal
      cell carcinoma (RCC) cell lines. After the transplantation of RCC cells into nude
      mice, we administered IFN (PEG-IFN-alpha2b or IFN-alpha2b) alone, 5-FU alone, or
      IFN (PEG-IFN-alpha2b or IFN-alpha2b) plus 5-FU; and investigated tumor volume,
      tumor weight, the numbers of apoptotic cells and artery-like blood vessels,
      relative mRNA expression levels of enzymes which relate to 5-FU metabolism,
      angiogenesis factor, and type I interferon receptor. RCC cells in vitro were
      generally and relatively resistant to the anti-proliferative effects of PEG-IFN
      alpha2b, but the addition of 5-FU augmented IFN-induced anti-proliferative
      effects with the induction of apoptosis. PEG-IFN-alpha2b in vivo presented
      stronger anti-tumor effects than IFN-alpha2b, and its combination with 5-FU
      augmented the effects. The significant anti-tumor effect of the combination
      treatment was the increase in apoptotic cell number, but there were no
      significant differences in the suppression of angiogenesis, expression of IFN
      receptor, and the actions of metabolic enzymes of 5-FU. In conclusion, PEG-IFN
      alpha2b presents stronger anti-tumor effects than non-pegylated IFN, and the
      effects are augmented in the combination with 5-FU. Our findings suggest the
      clinical usefulness of PEG-IFN-alpha2b in the treatment of RCC.

PMID- 18813778
TI  - Dietary isothiocyanate mediated apoptosis of human cancer cells is associated
      with Bcl-xL phosphorylation.
AB  - Benzylisothiocyanate (BITC), a major phase II enzyme inducer in the organic
      solvent of papaya fruit, has been shown to induce apoptosis specifically in
      cancer cells. The exposure of pancreatic, prostate as well as leukemic cells to
      this dietary isothiocyanate resulted in significant extent of apoptosis as
      evident from PARP cleavage, chromatin condensation or profound attenuation of
      procaspase-3 level. We also investigated whether BITC induces apoptosis by
      converging two major pathways: the death receptor mediated extrinsic and the
      mitochondrial intrinsic pathway. The exogenous expression of dominant-negative
      caspase-8 or dominant-negative caspase-9 can attenuate BITC-mediated cell death
      of prostate cancer cells. In parallel with this observation, BITC can activate
      both procaspase-8 and -9 in pancreatic and prostate cancer cells. Furthermore,
      flow cytometry analysis demonstrated the enrichment of sub-G0-G1 phase population
      with G2-M arrest in BITC challenged pancreatic cancer cells. In order to
      comprehend the molecular mechanism underlying the relationship between BITC
      mediated cell cycle arrest and apoptosis we report here for the first time that
      the anti-apoptotic protein Bcl-xL was phosphorylated by BITC treatment.
      Subsequent investigation using Jun kinase inhibitor exhibits the involvement of
      Jun kinase in BITC triggered Bcl-xL phosphorylation and apoptosis.

PMID- 18813779
TI  - Targeting metastatic cancer from the inside: a new generation of targeted gene
      delivery vectors enables personalized cancer vaccination in situ.
AB  - The advent of pathotropic (disease-seeking) targeting technologies, combined with
      advanced gene delivery vectors, provides a unique opportunity for the systemic
      delivery of immunomodulatory cytokine genes to remote sites of cancer metastasis.
      When injected intravenously, such pathotropic nanoparticles seek out and
      accumulate selectively at sites of tumor invasion and neo-angiogenesis, resulting
      in enhanced gene delivery, and thus cytokine production, within the tumor
      nodules. Used in conjunction with a primary tumoricidal agent (e.g., Rexin-G)
      that exposes tumor neoantigens, the tumor-targeted immunotherapy vector is
      intended to promote the recruitment and activation of host immune cells into the
      metastastic site(s), thereby initiating cancer immunization in situ. In this
      study, we examine the feasibility of cytokine gene delivery to cancerous lesions
      in vivo using intravenously administered pathotropically targeted nanoparticles
      bearing the gene encoding granulocyte/macrophage colony-stimulating factor (GM
      CSF; i.e., Reximmune-C). In vitro, transduction of target cancer cells with
      Reximmune-C resulted in the quantitative production of bioactive and
      immunoreactive GM-CSF protein. In tumor-bearing nude mice, intravenous infusions
      of Reximmune-C-induced GM-CSF production by transduced cancer cells and paracrine
      secretion of the cytokine within the tumor nodules, which promoted the
      recruitment of host mononuclear cells, including CD40+ B cells and CD86+
      dendritic cells, into the tumors. With the first proofs of principle established
      in preclinical studies, we generated an optimized vector configuration for use in
      advanced clinical trial designs, and extended the feasibility studies to the
      clinic. Targeted delivery and localized expression of the GM-CSF transgene was
      confirmed in a patient with metastatic cancer, as was the recruitment of
      significant tumor-infiltrating lymphocytes (TILs). Taken together, these studies
      provide the first demonstrations of cytokine gene delivery to cancerous lesions
      following intravenous administration and extend the applications of cancer
      immunization in vivo.

PMID- 18813780
TI  - Low doses of paclitaxel potently induce apoptosis in human retinoblastoma Y79
      cells by up-regulating E2F1.
AB  - Paclitaxel (PTX) is an anticancer drug currently in phase II clinical trials.
      This study shows for the first time that low doses of PTX (5 nM) potently induce
      apoptosis in human retinoblastoma Y79 cells. The effect of PTX is accompanied by
      a potent induction of E2F1 which appears to play a critical role in the effects
      induced by PTX. PTX induced a dose- and time-dependent effect, with G2/M arrest,
      cyclines A, E and B1 accumulation and a marked modification in the status of Cdc2
      cyclin B1 complex, the major player of the G2/M checkpoint. Apoptosis followed
      G2/M arrest. An early and prolonged increase in p53 expression with its
      stabilization by phosphorylation and acetylation and its nuclear translocation
      occurred. Consistently, PTX increased p21WAF1, bax and MDM2 levels, suggesting
      that p53 is transcriptionally active. p53 accumulated following both E2F1 up
      regulation and increase in the levels of p14ARF which interacts with MDM2
      preventing ubiquitination and proteosomal degradation of p53. Both extrinsic
      (E2F1/Fas/JNK/caspase-2 activation) and intrinsic (Bcl-2 phosphorylation, Bid
      fragmentation and Bax increase) pathways seemed to be involved. Loss of
      mitochondrial potential and activation of apoptosome and executive caspase-3,-6
      and-7 was shown. Incubation with either the irreversible pan-caspase inhibitors Z
      VAD-FMK, or SP600125, a selective inhibitor of JNK, or pifithrin alpha, a potent
      p53 inhibitor, significantly inhibited the effects induced by PTX.

PMID- 18813781
TI  - Tailor-made approach to photodynamic therapy in the treatment of cancer based on
      Bcl-2 photodamage.
AB  - It is very important to elucidate the mechanism of action and identify the
      molecular determinant of photodynamic medicine, in order to increase the number
      of clinical applications of photodynamic therapy (PDT) and perform personalized
      medicine. We have previously reported that PDT using some photosensitizers, such
      as phthalocyanine 4 (Pc 4) damages the anti-apoptotic protein Bcl-2, and that Bcl
      2 is a molecular PDT target using a mitochondrion-targeting photosensitizer. In
      this study, we examined the molecular targets of Photofrin-PDT and NPe6-PDT,
      which are approved for early stage lung cancers by the Japanese Ministry of
      Health Labor and Welfare, by evaluating the photodamage to Bcl-2 using Western
      blot analysis. Our results showed that Photofrin-PDT damaged Bcl-2, induced
      morphologically typical apoptosis, and demonstrated equal sensitivity between MCF
      7c3 cells (human breast cancer cells expressing stably transfected procaspase-3)
      and Bcl-2 overexpressing cells, MCF-7c3-GFP-Bcl-2 cells, with a clonogenic assay.
      However, NPe6-PDT did not damage Bcl-2 and took longer to induce typical
      apoptosis compared with Photofrin-PDT. MCF-7c3-GFP-Bcl-2 cells were considerably
      more resistant to the lethal effects of NPe6-PDT than parental MCF-7c3 cells. In
      conclusion, Photofrin-PDT damages different molecular targets, and our data
      indicate that the extent of Bcl-2 photodamage can determine the sensitivity of
      cancer cells to apoptosis and to overall cell killing caused by PDT using
      Photofrin, but not the lysosomal targeting NPe6. The application of these
      findings to clinical PDT may depend on the levels of the Bcl-2 proteins in the
      tumor being treated, and the tailor-made medicine based on the Bcl-2 photodamage
      may overcome any resistance afforded by elevated amounts of Bcl-2.

PMID- 18813782
TI  - Autocrine and/or paracrine growth of aggressive ATLL cells caused by HGF and c
      Met.
AB  - Adult T-cell leukemia/lymphoma (ATLL) is a neoplasia characterized by the massive
      invasion of various organs by tumor cells. Previously, we found that expression
      of the gene for c-Met, a receptor tyrosine kinase for hepatocyte growth factor
      (HGF), was specific to the acute type among 41 patients with ATLL by microarray.
      First in the present study, we analyzed the survival of the patients in relation
      to expression of c-Met and HGF in ATLL cells. Expression of the former but not
      the latter was associated with poor prognosis. Then, we analyzed the growth of
      ATLL cells caused by HGF and c-Met. c-Met was expressed in 0/7 chronic ATLLs,
      12/14 acute ATLLs, 1/1 IL-2-independent ATLL cell line and 1/7 IL-2-dependent
      ATLL cell lines as assessed by flow cytometry. HGF induced the proliferation of
      primary cells from most acute cases examined as well as the c-Met-positive KK1
      cell line in contrast to c-Met-negative cells. HGF induced autophosphorylation of
      c-Met in c-Met-positive cells from an acute case and KK1 cells. The plasma level
      of HGF was elevated in acute as compared to chronic cases. The levels of HGF
      and/or IL-6 which induces the production of HGF by stromal cells, were elevated
      in the supernatant of short-term cultured cells from certain patients with acute
      or chronic disease. Finally, infiltrated ATLL cells and adjacent stromal cells in
      liver were shown to be positive for c-Met/HGF and HGF, respectively, in acute
      cases. Autocrine and/or paracrine growth caused by HGF and c-Met was suggested in
      aggressive ATLL cells secreting HGF and/or IL-6, respectively.

PMID- 18813783
TI  - Response of brain specific microenvironment to P-glycoprotein inhibitor: an
      important factor determining therapeutic effect of P-glycoprotein inhibitor on
      brain metastatic tumors.
AB  - P-glycoprotein (P-gp), a factor responsible for the multidrug resistance of
      tumors, is specifically expressed in brain microenvironment. To test its roles in
      brain metastatic tumor chemoresistance, we implanted the paclitaxel-sensitive
      melanoma cell line, K1735, into the skin or brain of mice and examined its
      paclitaxel resistances. When implanted into the skin, paclitaxel inhibited tumor
      growth, however, it had no inhibitory effect on cells implanted into the brain.
      The paclitaxel resistance of the brain K1735 tumors was eliminated by combined
      treatment with a P-gp inhibitor, HM30181A, and paclitaxel. Previously we found
      that there is a defined therapeutic window for combined treatment of brain tumors
      with HM30181A and paclitaxel. To determine whether it is due to responses of the
      brain microenvironment we measured changes in P-gp expression and function of
      brain endothelial cells in response to HM30181A treatment in vitro and in vivo.
      They were significantly increased by high-dose HM30181A treatment and it was
      related with the therapeutic effect loss of high-dose HM30181A treatment.
      Therefore, P-gp in the brain microenvironment has crucial roles in the brain
      metastatic tumor chemoresistance and brain microenvironment responses to P-gp
      inhibitor treatment should be considered in the development of brain endothelial
      cell-targeted chemotherapy using P-gp inhibitor.

PMID- 18813784
TI  - Regulation of p63 expression in primary and immortalized nasopharyngeal
      epithelial cells.
AB  - Mutation of the p53 gene is a common event in human cancer. Interestingly, p53
      mutation is uncommon in nasopharyngeal carcinoma (NPC). The DeltaNp63 has been
      postulated to have a dominant-negative effect on the function of the p53 gene and
      may play a role in the pathogenesis of nasopharyngeal carcinoma. Immortalization
      is a common property of cancer cells and is believed to be an early event in
      carcinogenesis. At present, the relationship between DeltaNp63 and
      immortalization is poorly understood. In this study, we defined the expression
      profile of p63 and its various isoforms in primary and immortalized
      nasopharyngeal epithelial cells. Also, we elucidated some events regulating the
      expression of p63. Elevated expression of p63 was generally detected in both
      primary and immortalized nasopharyngeal epithelial cells at their proliferation
      stage and the predominant isoform of p63 expressed was DeltaNp63alpha. p63
      expression was suppressed upon cellular senescence of primary nasopharyngeal
      epithelial cells and induction of terminal differentiation in immortalized
      nasopharyngeal epithelial cells. Expression of DeltaNp63 alone was able to drive
      clonal proliferation in primary nasopharyngeal cells in culture while
      downregulation of DeltaNp63 induced cellular apoptosis. All these results support
      a role of DeltaNp63 in proliferation and immortalization which facilitates
      pathogenesis of nasopharyngeal carcinoma. TGFbeta and retinoic acid downregulated
      the expression of p63 in immortalized nasopharyngeal epithelial cells and may
      play a role in regulating differentiation in squamous epithelial cells with
      potential applications in prevention and treatment of nasopharyngeal carcinoma.

PMID- 18813785
TI  - Glycolysis module activated by hypoxia-inducible factor 1alpha is related to the
      aggressive phenotype of hepatocellular carcinoma.
AB  - An increased level of glycolysis, an intracellular hallmark of neoplasms, enables
      cancer cells to survive under various conditions. To elucidate the role of
      increased glycolysis in the progression of hepatocellular carcinoma (HCC), we
      investigated the associations between the expression patterns of 14 glycolysis
      related genes and clinicopathologic factors in 60 HCCs by using pooled
      transcriptome data. We then evaluated the therapeutic efficacy of the knockdown
      of ENO1, which is encoded by a glycolysis-related gene, in HCC cells. Among the
      14 genes, levels of 8 genes (GPI, ALDOA, TPI1, GAPD, PGK, PGAM, ENO1 and PKM),
      all of which can be transcriptionally activated by hypoxia-inducible factor
      1alpha (HIF-1alpha), were significantly higher in HCC with venous invasion (VI)
      than in HCC without VI. Our cluster analysis showed that HCC patients with
      activation of the 8 HIF-1alpha-regulated genes had significantly shorter overall
      survival (P=0.023) than did HCC patients without increased expression levels of
      these genes. The association between the levels of ENO1 and VI was confirmed in
      an independent sample set of 49 HCCs by real-time reverse-transcription PCR. The
      knockdown of ENO1 by small-interfering RNA significantly inhibited the
      proliferation of an HCC cell line (HLE cells) in both the glucose-rich and
      glucose-free conditions, accompanied by a decreased S phase and increased G2/M
      phase of the cell cycle. Collectively, these data suggest that activation of an
      HIF-1alpha-regulated glycolysis module is closely related to the aggressive
      phenotype of HCC, and that ENO1, a glycolysis module gene, might serve as a new
      target to circumvent HCC metastasis.

PMID- 18813786
TI  - The dual EGF/VEGF receptor tyrosine kinase inhibitor AEE788 inhibits growth of
      human hepatocellular carcinoma xenografts in nude mice.
AB  - We investigated the effect of AEE788, a novel dual receptor tyrosine kinase
      inhibitor of the EGF and the VEGF receptor, for treatment of human HCC cell lines
      and in a subcutaneous xenograft model. Cell viability and apoptosis of HepG2 and
      Hep3B cells incubated with 0.1-100 microM AEE788 were quantified. In vivo, HepG2
      cells were xenografted to NMRI mice and animals were treated orally with 50 mg/kg
      AEE788 3x/week. Immunohistochemistry and quantitative Western blotting was
      performed for pathway analysis in vitro and in vivo. AEE788 reduced growth and
      induced apoptosis of HCC cells by disrupting mitochondrial transmembrane
      potentials and inhibiting MAPK phosphorylation. In the xenografts, AEE788 lead to
      a reduced tumor growth by reducing proliferation and vascularisation. Except for
      a reversible skin reaction and weight loss, no signs of toxicity were observed.
      AEE788 is a promising new option for the treatment of HCC.

PMID- 18813787
TI  - p28GANK knockdown-derived reactive oxygen species induces apoptosis through
      mitochondrial dysfunction mediated by p38 in HepG2 cells.
AB  - Oncoprotein p28GANK knockdown by RNA interference (RNAi) can induce hepatoma
      cells apoptosis. However, the mechanisms have not been well defined yet. In the
      present study the p28GANK knockdown-induced apoptosis in HepG2 cells was
      prevented by caspase-9 inhibitor (Z-LEHD-FMK). During the knockdown of p28GANK,
      mitochondrial translocation of Bax, loss of mitochondrial transmembrane potential
      (DeltaPsim) and release of cytochrome c were observed. In this study, the
      activation of p38 was found to be critical for the p28GANK knockdown-induced
      apoptosis, as suggested by the finding that pharmacological inhibition of p38
      with SB203580 suppressed the redistribution of Bax, the loss of DeltaPsim and the
      apoptosis. Moreover, generation of reactive oxygen species (ROS) contributed to
      the cell death because N-acetyl-L-cystenine (NAC), a ROS scavenger, suppressed
      the phosphorylation of p38 and the apoptosis. Our studies established the
      signaling pathway of p28GANK knockdown-induced apoptosis in HepG2 cells, namely,
      mitochondrial dysfunction mediated by p38 downstream of intracellular ROS
      generation.

PMID- 18813788
TI  - Prevention and delay in progression of human squamous cell carcinoma of the head
      and neck in nude mice by stable overexpression of the opioid growth factor
      receptor.
AB  - This study examined overexpression of the opioid growth factor receptor (OGFr) in
      squamous cell carcinoma of the head and neck and phenotypic repercussions on
      tumorigenicity. Tumors from 3 SCC-1 cell lines (OGFr-9, OGFr-18, OGFr-22) stably
      transfected with OGFr cDNA (OGFr-1) had 2.5- to 3.7-fold more OGFr than empty
      vector (EV) or wild-type (WT) neoplasias. No differences in OGFr number were
      detected between tumors of EV and WT animals. Only 16 and 28% of the mice in the
      OGFr-18 and OGFr-22 groups, respectively, receiving 2 million tumor cells had a
      measurable tumor on day 12 compared to 70% of the EV group; 25% of the OGFr-22
      animals given 5 million cells expressed a tumor relative to the EV group (100%).
      Latencies for tumor appearance were extended by 25 and 80% for animals in the
      OGFr-18 and OGFr-22 groups, respectively, compared to EV animals given 2 million
      cells, and were lengthened by 2-fold in OGFr-22 animals injected with 5 million
      cells. Tumor weight of all animals overexpressing OGFr were 48-67% of EV mice,
      and the number of cells undergoing DNA synthesis in these tumors with amplified
      OGFr was reduced 46-65% of the EV group. Tumor volumes of OGFr-9 animals
      inoculated with 2 million cells and followed for over 7 weeks were reduced 36-70%
      from the WT group on days 31-54. Tumor weights on day 54 for the OGFr-9 group
      were 2.6-fold less than those for the WT animals. These data support OGFr gene
      function as a regulator of cell proliferation that impacts on tumorigenic
      expression of SCCHN, and suggests that molecular and pharmacological manipulation
      of OGFr may prevent or delay human head and neck squamous cell cancers.

PMID- 18813789
TI  - Glioma gene therapy with soluble transforming growth factor-beta receptors II and
      III.
AB  - Transforming growth factor-beta (TGF-beta) is abundantly expressed in malignant
      gliomas and is crucial for the tumor micromilieu. TGF-beta not only enhances
      migration and invasion of glioma cells but also inhibits an effective anti-glioma
      immune response. TGF-beta mediates its biologic effects through interactions with
      TGF-beta receptors (TbetaR)-I to -III. Binding of TGF-beta leads to the
      activation of an intracellular signaling cascade and subsequent phosphorylation
      of Sma and MAD-related proteins (SMAD). Soluble TGF-beta receptors (TbetaRs)
      abrogate the TGF-beta effect by competing for the binding of the ligand to its
      receptor. Here we used adenoviral gene transfer to express TbetaR-IIs and -IIIs
      in human glioma cell lines. TbetaR-IIs reduced SMAD2 phosphorylation and TGF-beta
      dependent reporter activity. Furthermore, it enhanced glioma cell lysis by
      natural killer cells. TbetaR-IIIs alone were inactive in these assays, but
      enhanced the effects of TbetaR-IIs. Transduction of LN-308 cells with TbetaRs
      markedly delayed growth of intracerebral xenografts in nude mice in vivo. These
      data commend TbetaRs for possible experimental therapy of gliomas.

PMID- 18813790
TI  - Histone deacetylase inhibitor scriptaid induces cell cycle arrest and epigenetic
      change in colon cancer cells.
AB  - Histone deacetylase inhibitors (HDACIs) are involved in cell growth, apoptosis
      and differentiation. This study aimed to investigate the effects of HDACI
      scriptaid on histone modification, demethylation, cell growth, cell cycle and
      apoptosis in the RKO colorectal cancer cell line and screening for scriptaid
      induced genes. RKO cells were treated with 5-aza-2'-deoxycytidine (5-aza-dC),
      trichostatin A (TSA) or scriptaid at different concentrations. Histone
      modification and methylation status of a silenced p16 gene were analyzed using
      chromatin immunoprecipitation and methylation-specific PCR, respectively. Flow
      cytometry was performed for the analysis of cell cycle and apoptosis. Scriptaid
      induced expression was analyzed using Human OneArray chip. Scriptaid resulted in
      the demethylation and re-expression of a hypermethylated p16 gene along with 5
      aza-dC synergistically in the RKO cells, but not alone. Scriptaid induced
      modifications of core histone tails important in euchromatin structure: increases
      in acetyl-H3-K9 and dimethyl-H3-K4 and a decrease in dimethyl-H3-K9. Cell growth
      was inhibited by scriptaid in a dose-dependent manner. Cell cycle analysis showed
      that scriptaid induced G1 arrest at 0.5 and 1.0 microM concentrations and G1 and
      G2/M arrest at 2.0 microM. Scriptaid did not have a significant effect on
      apoptosis in RKO cells. An altered expression of 278 genes was observed in RKO
      cells in response to scriptaid treatment. In conclusion, the present study
      suggests that scriptaid may be effective in growth suppression and cell cycle
      arrest and in the reversal of repressive chromatin marks at the promoter region
      of a hypermethylated p16 gene in colorectal cancer.

PMID- 18813791
TI  - HIV-1 Tat enhances replicative potential of human oral keratinocytes harboring
      HPV-16 genome.
AB  - Introducing highly active antiretroviral therapy (HAART) has significantly
      decreased the morbidity and mortality in human immunodeficiency virus-positive
      (HIV+) individuals by decreasing the viral loads and increasing the CD4+ T-cell
      counts. Subsequently, the occurrence of many HIV-associated diseases has been
      dramatically declined except human papillomavirus (HPV)-associated lesions. Such
      notion suggests that immune response is not a major determinant, and that the
      direct interaction between HIV and HPV may be involved in the HPV-associated
      pathogenesis. In the current study, we investigated whether HIV plays a direct
      role in HPV-associated oral carcinogenesis by using HIV-1 transactivator protein
      (Tat), which is known to have oncogenic properties. We found that HIV-1 Tat not
      only increased the expression of HPV-16 E6 and E7 oncogenes in human oral
      keratinocytes harboring the HPV type-16 genome (HOK-16B), but also notably
      enhanced the proliferative capacity of the cells in vitro. Moreover, HOK-16B
      cells expressing HIV-1 Tat was capable of inducing cystic nodules in nude mice,
      while the control HOK-16B cells failed to produce nodules in the mice. Our
      results indicate that HIV could play a role in the HPV-associated pathogenesis by
      exerting oncogenic stimulus via Tat protein.

PMID- 18813792
TI  - Simultaneous downregulation of uPAR and MMP-9 induces overexpression of the FADD
      associated protein RIP and activates caspase 9-mediated apoptosis in gliomas.
AB  - We have previously demonstrated the effectiveness of simultaneous RNA
      interference (RNAi)-mediated downregulation of urokinase-type plasminogen
      activator receptor (uPAR) and matrix metalloproteinase-9 (MMP-9) in inhibiting
      tumor invasion in vitro and in vivo. In particular, we have shown that the
      downregulation of uPAR and MMP-9 inhibits intracranial tumor growth. The
      mechanism of the inhibition of tumor growth has not yet been determined. In this
      study, we have attempted to explain the mechanisms involved in the inhibition of
      invasiveness and tumor growth in vitro. SNB19 glioma cells were transfected with
      scrambled vector plasmid (pSV) and a siRNA-expressing plasmid targeting either
      uPAR (pU) or MMP-9 (pM) singly or in combination (pUM). Untransfected cells were
      also used as a control. Western blotting and RT-PCR analyses showed the
      downregulation of uPAR in pU-transfected cells and MMP-9 in pM-transfected cells.
      In cells transfected with pUM, we observed down-regulation of both uPAR and MMP
      9, thereby indicating the specificity of the siRNA-expressing plasmids. An
      increase in caspase 9 expression was observed in cells transfected with pUM
      whereas no change in the level of caspase 9 was observed in pU or pM-transfected
      cells. Additionally, no change in the expression level of caspase 8 was observed.
      However, an increase in the expression level of cleaved PARP was observed in the
      case of cells transfected with pU, pM and pUM. Cells transfected with pUM showed
      the highest levels of cleaved PARP expression. Expression levels of APAF-1 were
      also higher in pUM-transfected cells with no change in expression levels of
      controls and in pU and pM-transfected cells. Total CAD expression levels did not
      change under any of the transfection conditions. However, immunohistochemical
      studies demonstrated that CAD was translocated to the nucleus, thereby indicating
      DNA damage. As determined by Western blot analysis of subcellular fractions,
      cytoplasmic levels of cytochrome c were also increased. We determined the extent
      of DNA damage using the TUNEL assay (poly-A termination of free -OH ends of
      degraded nuclear DNA). Based on our results we conclude that the simultaneous
      downregulation of uPAR and MMP-9 induces apoptosome-mediated apoptosis.

PMID- 18813793
TI  - Clusterin: a potential target for improving response to antiestrogens.
AB  - Antiestrogens represent the first line of therapy in the treatment of estrogen
      receptor-positive (ER+) breast cancer patients. Unfortunately, up to 40% of
      patients develop resistance associated with progression and frequently die for
      metastatic breast cancer. The molecular events leading to pharmacological
      resistance are not completely understood. We attempted to verify in an
      experimental model the role of cytoplasmic clusterin (CLU), a cytoprotective
      protein found to be up-regulated in antiestrogen-resistant patients, following
      neoadjuvant treatment with toremifene. The role of cytoplasmic clusterin in
      modulating response to two antiestrogens (toremifene and tamoxifen) was studied
      in two ER+ anti-estrogen-sensitive cell lines (MCF-7, 734B) and one ER+
      antiestrogen-resistant cell line (T47D) using siRNA strategy. Resistant cells
      were characterised by higher levels of cytoplasmic clusterin than sensitive
      cells, and antiestrogen treatments up-regulated clusterin levels in both
      sensitive and resistant cell lines. Treatment with siRNA completely abolished
      cytoplasmic clusterin expression in all cell lines, but its down-regulation
      resulted in a significant decrease of cell growth only in the resistant line. We
      therefore concluded that: i) basal clusterin levels are higher in antiestrogen
      resistant cells, ii) clusterin is up-regulated following antiestrogen treatment
      independently of the sensitivity of the cell line, iii) down-regulation of
      cytoplasmic clusterin restores sensitivity to toremifene in the antiestrogen
      resistant cell line. Such results support the concept that targeting CLU could
      represent a promising therapeutic strategy in association with antiestrogen
      treatment in breast cancer patients.

PMID- 18813794
TI  - Pharmacokinetic and pharmacodynamic study of NO-donating aspirin in F344 rats.
AB  - Nitric oxide-donating aspirin (NO-ASA) represents class of promising
      chemopreventive NO-NSAIDs. NO-ASA combines the beneficial effects of ASA and the
      gut-sparing effect of the NO moiety. There is, however, limited information on
      its pharmacokinetic and pharmacodynamic effects in vivo. Herein, experiments were
      designed to identify the optimal dose, the effective route of administration, and
      targeted markers in plasma and colonic tissues of male F344 rats. Seven weeks old
      male F344 rats were randomized into 9 groups (16/group) and fed the control diet.
      At eight weeks of age, groups 2-5 were each administered one of four different
      doses of NO-ASA by gavage (33, 66, 132 and 264 mg/kg) and each of groups 6-9 were
      fed diets containing NO-ASA (35, 700, 1,400 and 2,800 ppm) for two weeks. Rats
      were sacrificed 2 and 10 h after completion of the two weeks of treatment with NO
      ASA and plasma and colonic mucosa were collected and analyzed for NO-ASA, its
      metabolites, and PGE2 and TXB2 levels. Our results indicate that NO-ASA is
      rapidly metabolized, predominantly to salicylic acid; no intact NO-ASA was
      detected in plasma. Compared to diet-fed NO-ASA, gavaging generated much higher
      salicylic acid levels over a wide range of doses and a relatively broad time
      period (10 h). Regardless of its route of administration, NO-ASA lowered the
      levels of PGE2 in colonic tissues and plasma, as well as TxB2 in plasma in a dose
      and time-dependent manner. These findings may have practical utility for the
      administration of NO-ASA to humans.

PMID- 18813795
TI  - Induction of cell cycle arrest and apoptosis in myeloma cells by cepharanthine, a
      biscoclaurine alkaloid.
AB  - Cepharanthine (CEP), a biscoclaurine alkaloid extracted from Stephania
      Cepharantha Hayata, has been used in Japan for treating patients with radiation
      induced leucopenia or thrombocytopenia. We treated a patient with multiple
      myeloma (MM), who was not responding to preceding chemotherapy, who coincidently
      received therapy with CEP due to thrombocytopenia. Since the case showed a marked
      reduction of tumor load, direct anti-tumor effects of CEP to myeloma cells were
      investigated in vitro. Anti-tumor effects were observed in all myeloma cell lines
      tested, including a line resistant to melphalan. Exposure to CEP of a myeloma
      cell line induced the production of reactive oxygen species, activated the
      caspase-3 pathway and eventually induced apoptosis. Pre-exposure of cells to a
      pan-caspase inhibitor, Z-VAD-FMK, or a free radical scavenger, Tiron, effectively
      blocked CEP-induced apoptosis. Interestingly, CEP also inhibited cell growth of
      myeloma cells by inducing CDK inhibitors. These data show, for the first time,
      that CEP has anti-myeloma effects by the activation of apoptotic pathways and
      blocking cell cycle progression via CDK inhibitors. Although analysis of these
      two pathways should be clarified further, the use of CEP may be considered as a
      potential therapeutic agent for a subset of MM.

PMID- 18813796
TI  - MYCN downregulates integrin alpha1 to promote invasion of human neuroblastoma
      cells.
AB  - Neuroblastoma is a childhood tumor thought to arise through improper
      differentiation of neural crest cells. MYCN amplification is a prognostic factor
      that indicates a highly malignant disease and poor patient prognosis. Integrins
      are important regulators of neuroblastoma attachment and migration and
      participate in many aspects of metastasis. However, the role of integrins in
      neuroblastoma metastasis, the leading cause of death from this disease, remains
      less well understood. Screening of neuroblastoma cell lines for integrin mRNA
      expression showed that integrin alpha1 expression was higher in lines such as SK
      N-SH and NB69 that do not have MYCN amplification than in cell lines such as
      IMR32, NB1, NB9 and NB19 that have MYCN amplification. A knockdown of MYCN in NB1
      and NB19 cells resulted in increased expression of integrin alpha1, which
      correlated with enhanced attachment to the extracellular matrix and reduced
      migratory activity. In contrast, the overexpression of MYCN in SK-N-SH and NB69
      cells resulted in decreased expression of integrin alpha1, which correlated with
      reduced attachment to the extracellular matrix and enhanced migratory activity.
      These results show that MYCN may limit cell adhesion to the extracellular matrix
      and promote cell migration by downregulating integrin alpha1.

PMID- 18813797
TI  - Activation of human T cells by a tumor vaccine infected with recombinant
      Newcastle disease virus producing IL-2.
AB  - A new recombinant (rec) Newcastle disease virus (NDV) with incorporated human
      interleukin 2 (IL-2) as foreign therapeutic gene [rec(IL-2)] will be described.
      The foreign gene in rec(IL-2) did not affect the main features of NDV replication
      nor its tumor selectivity. Biologically active IL-2 was produced in high amounts
      by tumor cells infected with rec(IL-2). Tumor vaccine cells infected by rec(IL-2)
      stimulated human T cells to exert anti-tumor activity in vitro in a tumor
      neutralization assay. These effects were significantly increased when compared to
      vaccine infected by rec(-) virus without IL-2 gene. After incubation with rec(IL
      2) infected tumor cells, T cells showed increased expression of the activation
      marker CD69 and produced increased amounts of IFNgamma when compared to T cells
      co-incubated with rec(-) infected tumor cells. CD8 T cells incubated with rec(IL
      2) infected tumor cells showed upregulation of perforin, cell surface exposure of
      the degranulation marker CD107a and increased anti-tumor cytotoxic activity.
      Purified T cells from lymph nodes of head and neck squamous cell carcinoma
      (HNSCC) patients could be stimulated to secrete IFNgamma in an ELISPOT assay upon
      40 h of stimulation with rec(IL-2) infected autologous tumor cells [ATV-rec(IL
      2)] but not upon stimulation with rec(IL-2) infected allogeneic U937 tumor cells.
      This suggests direct activation of patient derived tumor antigen-specific memory
      T cells by ATV-rec(IL-2). In conclusion, the already inherent immunostimulatory
      properties of NDV could be further augmented by the introduction of the
      therapeutic gene IL-2. Active specific immunization of patients with ATV-rec(IL
      2) should provide the microenvironment at the vaccination site with IL-2 and
      avoid side effects as seen after systemic IL-2 application.

PMID- 18813798
TI  - Control of cellular redox status and upregulation of quinone reductase NQO1 via
      Nrf2 activation by alpha-lipoic acid in human leukemia HL-60 cells.
AB  - alpha-Lipoic acid (LA) is a naturally-occurring micronutrient that has been
      actively investigated for the treatment and management of various chronic medical
      conditions including neurodegenerative diseases, diabetes and hepatic disorders.
      However, relatively few studies have examined the effects of LA as a
      chemopreventive agent, particularly in regard to its ability to modulate
      homeostasis of oxidoreductive state and to regulate detoxification enzymes such
      as quinone reductase NQO1 in LA-responsive cells. We tested the hypothesis that
      LA affects the intracellular redox status and induces NQO1 expression using the
      human promyelocytic HL-60 leukemia cells. We showed that treatment by LA
      maintains HL-60 cells in a relatively reduced state, supported by the dose/time
      dependent increase in the activities of glutathione peroxidase and glutathione
      reductase and decrease in the activity of catalase. Moreover, LA significantly
      increased the activity and protein expression of NQO1. The induction of NQO1 was
      accompanied by the nuclear accumulation of transcription factor Nrf2, which was
      correlated with a decreased level of Nrf2 in the cytosol as well as the
      concomitant reduction in the expression of cytoplasmic repressor of Nrf2, Keap1.

PMID- 18813799
TI  - Inhibition of Stearoyl-CoA Desaturase 1 expression in human lung adenocarcinoma
      cells impairs tumorigenesis.
AB  - Saturated (SFA) and monounsaturated (MUFA) fatty acids, the most abundant fatty
      acid species, have many divergent biological effects including the regulation of
      cell proliferation, programmed cell death and lipid-mediated cytotoxicity. Their
      distribution is regulated by Stearoyl-CoA Desaturases (SCD), the enzymes that
      convert SFA into MUFA. A positive correlation between high levels of tissue MUFA
      and several types of cancer has been reported, but a causal relationship between
      the function of SCD1, the main human SCD isoform, and cancer development has not
      yet been firmly established. Here we report that the stable knockdown of SCD1
      gene expression in A549 human lung adenocarcinoma cells decreased the ratio
      MUFA/SFA in total lipids and inhibited the incorporation of glucose into cell
      lipids. Cell proliferation and anchorage-independent growth were considerably
      decreased in SCD1-depleted cells, whereas the rate of apoptosis was elevated,
      with respect to control A549 cells. In addition, phosphorylation of Akt-Ser473
      and GSK-3beta-Ser9 was found notably impaired in SCD1-ablated A549 cells.
      Interestingly, the effects of SCD1 blockade on Akt activation, cancer cell growth
      and apoptosis could not be reversed by exogenously added oleic acid. Remarkably,
      the reduction of SCD1 expression in lung cancer cells significantly delayed the
      formation of tumors and reduced the growth rate of tumor xenografts in mice. Our
      study demonstrates that SCD1 activity regulates Akt activation and determines the
      rate of cell proliferation, survival and invasiveness in A549 cancer cells and
      shows, for the first time, that SCD1 is a key factor in the regulation of
      tumorigenesis in vivo.

PMID- 18813800
TI  - Suppression of cell proliferation and gene expression by combinatorial synergy of
      EGCG, resveratrol and gamma-tocotrienol in estrogen receptor-positive MCF-7
      breast cancer cells.
AB  - Numerous dietary phytochemicals have shown anti-breast carcinogenic activities
      when tested in vitro; however, in most cases, the demonstrated efficacy of
      individual phytochemicals requires doses not readily achievable in vivo.
      Therefore, whether diets might exert translational promises and benefits in
      clinical settings and prevention of breast cancer remain unclear. Since cancer
      cells are endowed with complex, redundant, converging and diverging pathways
      spanning both the genetic and metabolic networks that are not merely replicates
      of those in normal cells, it is of interest to test whether a multicomponent
      approach involving lower, physiologically relevant doses of natural dietary
      agents may be developed as a chemopreventive strategy for breast cancer. Herein,
      we investigated, using the estrogen receptor-positive MCF-7 breast cancer cells
      as a model, whether the combination of epigallocatechin gallate (EGCG),
      resveratrol and gamma-tocotrienol at suboptimal doses elicits synergism in
      suppressing cell proliferation, modulating gene expression, and increasing
      antioxidant activity, as compared to each of the three phytochemicals added
      alone. The results showed that there was a approximately 33, 50 and 58%
      inhibition of cell proliferation by > or =50 microM EGCG, > or =25 microM
      resveratrol and > or =10 microM gamma-tocotrienol, respectively, added as a
      single agent. When a suboptimal dose (10 microM) of each phytochemical was used,
      a significant additive effect in suppression of cell proliferation was observed
      with the combination of resveratrol and gamma-tocotrienol whereas the three
      phytochemicals added together did not produce more pronounced inhibition of cell
      proliferation. A significant additive effect in reducing cyclin D1 and bcl-2
      expression was found when gamma-tocotrienol was added with either EGCG or
      resveratrol. Functional synergism among the three phytochemicals was only
      observed in the induction of quinone reductase NQO1. These results suggest that
      diet-based protection against breast cancer may partly derive from synergy
      amongst dietary phytochemicals directed against specific molecular targets in
      responsive breast cancer cells, and provide support for the feasibility of the
      development of a diet-based combinatorial approach in the prevention and
      treatment of breast cancer.

PMID- 18813801
TI  - Gene-specific promoter hypermethylation without global hypomethylation in
      follicular thyroid cancer.
AB  - Genome-wide hypomethylation and hypermethylation at CpG promoters are common in
      cancer. To date, little is known about global methylation changes in follicular
      thyroid cancer (FTC). Two independent quantitative methods, bisulphite
      Pyrosequencing of Long Interspersed Nucleotide Elements-1 (LINE-1) and
      LUminometric Methylation Assay (LUMA) were used to quantify genome-wide
      methylation in 21 FTC and corresponding normal thyroid tissues. Unexpectedly
      global methylation was not found significantly altered in tumors compared to
      normal thyroid by either LINE-1 (p=0.57) or LUMA (p=0.42), whilst the promoter of
      a tumor suppressor that is often epigenetically dysregulated, RASSF1A was found
      to be significantly hypermethylated by Pyrosequencing (p=0.0001). Moreover,
      allelic imbalance at the RASSF1A locus was observed in 15/21 of the tumors. mRNA
      expression of RASSF1A was significantly lower in tumors compared to corresponding
      normal tissues (p=0.0002). In summary, the epigenetic inactivation of RASSF1A is
      a frequent event in FTC, but is not coupled to changes in global methylation.

PMID- 18813802
TI  - Premature chromosome condensation reveals DNA-PK independent pathways of
      chromosome break repair.
AB  - Cells of higher eukaryotes process double strand breaks (DSBs) in their genome
      using a non-homologous end joining apparatus that utilizes DNA-PK and other well
      characterized factors (D-NHEJ). Cells with defects in D-NHEJ, repair the majority
      of DSBs using a slow-repair pathway which is independent of genes of the RAD52
      epistasis group and functions as a backup (B-NHEJ). Recent studies implicate DNA
      ligase III, PARP-1 and histone H1 in this pathway of NHEJ. The present study
      investigates the operation of B-NHEJ in the repair of interphase chromosome
      breaks visualized in irradiated G0 human lymphocytes by premature chromosome
      condensation (PCC). Chromosome breaks are effectively repaired in human
      lymphocytes, but repair is significantly compromised after treatment with
      wortmannin, a DNA-PK inhibitor. Despite slower kinetics, cells exposed to
      wortmannin rejoin the majority of IR induced chromosome breaks suggesting that B
      NHEJ is also functional at the chromosome level. Complementation of D-NHEJ defect
      in wortmannin-treated lymphocytes by newly made DNA-PK is only possible under
      conditions of nuclear envelope break down and premature chromosome condensation,
      suggesting that in interphase cells the shunting of chromosome breaks from D-NHEJ
      to B-NHEJ is irreversible. The understanding of chromosomal aberration formation
      allows mechanistic explanations for the carcinogenic potential of D-NHEJ defects.

PMID- 18813803
TI  - Integrative genomic analyses on GLI2: mechanism of Hedgehog priming through basal
      GLI2 expression, and interaction map of stem cell signaling network with P53.
AB  - Hedgehog-binding to Patched family receptors results in Smoothened-mediated
      activation of MAP3K10 (MST) and inactivation of SUFU. MAP3K10-induced DYRK2
      phosphorylation combined with SUFU inhibition results in the stabilization and
      nuclear accumulation of GLI2 for transcriptional activation of GLI1, CCND1,
      CCND2, FOXA2, FOXC2, FOXP3, FOXQ1, RUNX2, and JAG2. Here, integrative genomic
      analyses on GLI2 orthologs were carried out. Rat Gli2 complete coding sequence
      was determined by assembling nucleotide sequences of exons 1, 2, and 5'-truncated
      rat Gli2 RefSeq (NM_001107169.1). GLI2 orthologs were more related to GLI3
      orthologs than to GLI1 orthologs lacking the N-terminal repressor domain.
      betaTRCP1 (FBXW1)-binding DSYxxxS motif was conserved in GLI2 and GLI3 orthologs,
      while betaTRCP2 (FBXW11)-binding DSGxxxxxxxxxS motif in GLI2 and GLI1 orthologs.
      Human GLI2 mRNA was expressed in ES cells, NT2 cells, fetal lung, fetal heart,
      regenerating liver, gastric cancer, and other tumors. Mouse Gli2 mRNA was
      expressed in unfertilized egg, ES cells, and EG cells. Tandem RRRCWWGYYY motifs
      for P53, P63 or P73, and also four conserved bHLH-binding sites were identified
      within GLI2 proximal promoter region. Interaction map of P53 and stem cell
      signaling network were then constructed. P53-induced NOTCH1 upregulation leads to
      HES1, HES5, HEY1, HEY2 or HEYL upregulation for the repression of tissue specific
      bHLH transcriptional activators. DYRK2 functions as a positive regulator of P53
      mediated apoptosis, and also as a negative regulator of the Hedgehog signaling
      cascade. GLI2 expression is regulated based on the balance of P53, Notch, and TGF
      beta signaling, and Hedgehog signaling activation results in cell survival and
      proliferation due to transcriptional activation of Hedgehog-target genes, and
      also partly due to perturbation of P53-mediated transcriptional regulation.

PMID- 18813804
TI  - Biochemical effects of piceatannol in human HL-60 promyelocytic leukemia cells-
      synergism with Ara-C.
AB  - Piceatannol (3,3',4,5'-tetrahydroxy-trans-stilbene; PCA) is a naturally occurring
      metabolite of resveratrol (3,4',5-trihydroxy-trans-stilbene; RV). In this study,
      we identified additional biochemical targets of PCA in human HL-60 promyelocytic
      leukemia cells. Incubation with PCA led to a significant proportion of apoptotic
      cells and caused an arrest in the G2-M phase of the cell cycle. PCA depleted
      intracellular dCTP and dGTP pools, and inhibited the incorporation of 14C-labeled
      cytidine into DNA. PCA significantly abolished all NTP pools, and sequential
      treatment with PCA and Ara-C yielded synergistic growth inhibitory effects
      because of remarkably increased Ara-CTP formation after PCA preincubation. Due to
      these promising results, PCA may support conventional chemotherapy of human
      malignancies and therefore, deserves further preclinical and in vivo testing.

PMID- 18813805
TI  - Methylation-associated silencing of TU3A in human cancers.
AB  - TU3A, located on 3p21.1, was originally identified as a candidate tumor
      suppressor gene in renal cell carcinoma (RCC). Recently, down-regulation of TU3A
      expression has been reported not only in RCC but also in other types of cancers.
      However, no studies have evaluated the mechanism underlying TU3A inactivation. In
      the present study, we first examined the expression and promoter CpG island
      methylation of TU3A in RCC. TU3A mRNA was slightly or not expressed in 3 RCC cell
      lines (ACHN, Caki-1 and NC65). Bisulfite sequencing of the TU3A promoter and
      treatment of the RCC cell lines with 5-aza-2'-deoxycytidine and/or trichostatin A
      revealed an association between TU3A expression and promoter hypermethylation.
      Next, we analyzed TU3A methylation in primary RCC by using combined bisulfite
      restriction analysis. Mean methylated fraction was 19.2% (range: 0-57.3%) in 53
      conventional RCCs and 2.3% (range: 0-12.7%) in 24 corresponding normal kidneys.
      We defined a methylation fraction of >20% as hypermethylation. TU3A
      hypermethylation was detected in 22 (41.5%) of 53 RCCs and significantly
      associated with advanced tumor stage (>T2 vs. T1 and T2: P=0.005, > or = N1 or M1
      vs. N0M0: P=0.001) and poor disease-specific survival (P=0.0038). Furthermore, we
      observed promoter hyper-methylation of TU3A in several types of cancer cell lines
      and primary cancers of the bladder and testis. To our knowledge, the present
      study is the first to demonstrate the epigenetic inactivation of TU3A in human
      cancers. The findings of this study warrant further study to investigate the role
      of TU3A methylation in cancer development.

PMID- 18813806
TI  - Predicting response to neoadjuvant chemotherapy in breast cancer: molecular
      imaging, systemic biomarkers and the cancer metabolome (Review).
AB  - The ability to predict the response to neoadjuvant chemotherapy (NAC) prior to or
      shortly after commencing treatment, in women with large or locally advanced
      breast cancers, would not only prevent patients from experiencing unnecessary
      drug morbidity but also reduce the high cost associated with drug usage and
      utilisation of resources with NAC. Ability to estimate residual cancer volume
      after NAC is of clinical relevance to subsequent therapeutic surgical options.
      Various approaches, using conventional histopathological characteristics and
      imaging modalities to evaluate and predict the response to NAC, have not been
      able to provide accurate and reliable data. Novel biomolecular imaging, new
      biomarkers and recent cancer genomic and proteomic profiling, introduced into
      clinical practice, have produced preliminary promising results. We describe and
      discuss these molecular characteristics and approaches and their applications to
      NAC in breast cancer management.

PMID- 18813807
TI  - Rac1 mediates phorbol 12-myristate 13-acetate-induced migration of glioblastoma
      cells via paxillin.
AB  - Previously, we reported that phorbol 12-myristate 13-acetate (PMA)-activated
      protein kinase C (PKC) induced Rac1 activation in A172 glioblastoma cells. In
      this study, we investigated the mechanism of PMA-activated PKC-induced migration
      of glioblastoma cells by focusing on Rac1. PMA-induced formation of lamellipodia
      and focal complexes following migration were blocked by inhibiting Rac1 with
      small interfering RNA (siRNA), implicating Rac1 in PMA-induced glioblastoma cell
      migration. PMA-activated PKC induced phosphorylation of c-jun N-terminal kinase
      (JNK), one of the downstream effectors of Rac1. Immunohistochemical analysis
      showed that phosphorylated JNK was translocated to paxillin-containing focal
      complexes upon PMA stimulation and that Rac1 siRNA blocked these phenomena. These
      results suggest that phosphorylated JNK functions in cell migration and that JNK
      phosphorylation and translocation are mediated by Rac1. Furthermore, inhibition
      of Rac1 reduced phosphorylation of paxillin, a focal adhesion component and a
      downstream effector of JNK, at serine 178 (Ser178). Paxillin phosphorylation at
      this site has been shown to be involved in cell migration. Immunohistochemical
      analysis detected phosphorylation of paxillin (Ser178) in focal complexes upon
      PMA stimulation that was blocked by Rac1 siRNA. SP600125, a JNK inhibitor, also
      blocked PMA-induced phosphorylation of paxillin and aggregation of phosphorylated
      paxillin (Ser178) in focal complexes. In conclusion, paxillin is a critical
      downstream effector of Rac1 that may be involved in PMA-stimulated migration
      presumably by modulating the integrity of focal complex formation.

PMID- 18813808
TI  - Activation of Akt-mTOR-p70S6K pathway in angiogenesis in hepatocellular
      carcinoma.
AB  - Angiogenesis is an essential process for progression of hepatocellular carcinoma
      (HCC). The Akt-mTOR-p70S6K signal pathway has been recognized for its roles in
      regulating neoangiogenesis. The role of activation of the pathway in HCC
      progression is poorly understood. This study aimed to evaluate the
      immunohistochemical expression of the phosphorylated forms of the three key
      constituent proteins (Akt, mTOR and p70S6K) of the Akt-mTOR-p70S6K signal pathway
      in HCC and non-HCC tissue. Formalin-fixed paraffin-embedded tissue sections of 51
      HCC, 9 hepatocellular adenoma (HCA), 48 cirrhotic nodules (CN) and 17 normal
      liver tissues (NLT) were immunostained for p-Akt, p-mTOR and p-p70S6K. The number
      of p-Akt and p-p70S6K-positive sinusoidal endothelial cells (SEC) and the
      intensity of immunostaining were significantly increased in HCC compared with HA,
      CN and NLT (p<0.01). p-mTOR in SEC tended to have an increased expression in SEC
      in HCC versus non-HCC tissue (p>0.05). There was a significant correlation
      between a high p-Akt and p-p70S6K expression, and a venous and capsular invasion
      of HCC. Our results suggest that activation of the Akt-mTOR-p70S6K pathway plays
      a significant role in HCC progression by promoting neoangiogenesis. Molecular
      strategies aimed at inhibiting this signal pathway may be of therapeutic use for
      the treatment of HCC.

PMID- 18813809
TI  - Lymphangiogenesis in kidney cancer: expression of VEGF-C, VEGF-D and VEGFR-3 in
      clear cell and papillary renal cell carcinoma.
AB  - The vascular endothelial growth factors VEGF-C, VEGF-D and its receptor, VEGFR-3,
      are overexpressed in different malignancies and associated with lymph node
      metastasis and poor prognosis. We analysed these factors in clear cell (ccRCC)
      and papillary (pRCC) renal cell carcinoma (RCC). The results were correlated with
      various clinicopathological parameters (CPP). We constructed a tissue microarray
      with tumor samples of 135 (81%) ccRCC and 31 (19%) pRCC. After
      immunohistochemical staining using polyclonal antibodies for VEGF-C, VEGF-D and
      VEGFR-3, a semiquantitative analysis was performed to determine the levels of
      expression. The results were compared between the two subgroups and were
      correlated with CPP. In the two subgroups the expression of VEGF-C was
      significantly correlated with that of VEGF-D (p<0.001). There was an increased
      expression of VEGF-C in 11% of ccRCC and 36% of pRCC (p=0.002). VEGF-D expression
      was positive by means of analysis in 22% of ccRCC and 42% of pRCC (p=0.039).
      There was no significant difference regarding the expression of VEGFR-3 between
      the subgroups (44% ccRCC and 61% pRCC, p=0.11). No correlation was found between
      the expression of the analysed parameters and CPP (TNM, grading, progression-free
      survival and overall survival) in either the entire group or in the two
      subgroups. In summary, ccRCC and pRCC show a different expression pattern of the
      analysed lymphangiogenic factors. Further studies are necessary to confirm these
      results and to determine whether the VEGF-C/VEGF-D/VEGFR-3-axis can play a role
      as a prognostic tool or a target for therapeutic intervention in renal cell
      carcinoma.

PMID- 18813810
TI  - Metabolism of irinotecan and its active metabolite SN-38 by intestinal microflora
      in rats.
AB  - One of the dose-limiting toxicities of irinotecan (CPT-11) is delayed-onset
      diarrhea, which is the greatest barrier to treatment with CPT-11-containing
      regimens. CPT-11 is converted to its active metabolite, SN-38, which is
      conjugated by hepatic uridine diphosphate glucuronosyl transferase to SN-38
      glucuronide (SN-38G). SN-38G, once excreted in the intestinal lumen via bile, is
      extensively deconjugated by bacterial beta-glucuronidase with the regeneration of
      SN-38 in the intestinal lumen, which may cause diarrhea. However, the metabolism
      of CPT-11 and its metabolites by intestinal microflora are yet to be reported.
      This study was carried out to investigate the microbial transformation of CPT-11
      and SN-38 using an anaerobic mixed culture of rat cecal microorganisms. No
      reaction in the mixed cultures was observed when CPT-11 or SN-38 lactone was
      added to the culture medium. When CPT-11 was added to the culture broth, a
      significant amount of water-soluble CPT-11 was detected in the spent culture
      medium. In contrast, only a slight amount of SN-38 was found in the supernatant
      when SN-38 lactone was added to the broth. A significant quantity of SN-38 was
      found in the sediment. In conclusion, these results strongly suggest that SN-38
      produced from SN-38G by the action of bacterial beta-glucuronidase is rapidly
      adsorbed by the intestinal bacterial cell walls in the sediment because of the
      hydrophobic and lipophilic nature of SN-38, and a small amount of SN-38 remains
      in the intestinal luminal fluid. Thus, we need to reconsider the role of SN-38 in
      the intestinal lumen in CPT-11-induced late-onset diarrhea.

PMID- 18813811
TI  - Reversal of P-glycoprotein-mediated multidrug resistance in human sarcoma MES
      SA/Dx-5 cells by nonsteroidal anti-inflammatory drugs.
AB  - Multidrug resistance (MDR) mediated by P-glycoprotein (P-gp) is one of the major
      reasons for the failure of cancer therapy. Several chemosensitizers are able to
      reverse in vitro MDR by inhibiting P-gp, although high toxicity limits their
      clinical application. In this study, we aimed to investigate the in vitro
      effectiveness of four common non-steroidal anti-inflammatory drugs (NSAIDs) such
      as Curcumin (Cur), Sulindac (Sul), Ibuprofen (Ibu) and NS-398 (NS) to inhibit P
      gp activity at clinically achievable doses and to evaluate their potential use as
      sensitizers in anti-cancer chemotherapy. The human doxorubicin (doxo) resistant
      uterine sarcoma cells (MES-SA/Dx-5) expressing high levels of P-gp, were treated
      with different doxo concentrations in the presence or absence of NSAIDs. Cellular
      accumulation of doxo, cytotoxicity and apoptosis induction were measured in
      comparison with Verapamil, a specific P-gp inhibitor, used as a reference
      molecule. We found that Ibu, Cur and NS-398 enhanced significantly doxo
      retention, cytotoxicity and apoptosis on resistant MES-SA/Doxo-5 cells when
      compared with doxo alone. In contrast, no significant changes were found in
      resistant cells treated with Sul-doxo combinations. Our results demonstrate that
      Ibu, Cur and NS-398 below their therapeutic plasma concentrations were able to
      overcome P-gp-mediated MDR in MES-SA/Dx-5 cells. These findings provide the
      rationale for clinical studies of NSAIDs and/or derivatives as a new potential
      generation of chemosensitizers to improve effectiveness of the anti-cancer drugs
      in the treatment of human cancer.

PMID- 18813812
TI  - Liver metastasis of colorectal cancer by protein-tyrosine phosphatase type 4A, 3
      (PRL-3) is mediated through lymph node metastasis and elevated serum tumor
      markers such as CEA and CA19-9.
AB  - Phosphatase of regenerating liver (PRL)-3 was identified as a molecule associated
      with liver metastasis in colorectal cancer (CRC), although its precise causative
      role in distant metastasis remains elusive from a clinical point of view. The aim
      of this study was to promote the mechanistic insight of PRL-3 involvement in
      liver metastasis in CRC. One hundred and seven CRC patients with resection of the
      primary lesions were studied for clinicopathological and prognostic association
      with PRL-3 and were evaluated by immunohistochemistry in univariate and
      multivariate analyses. Intense immunostaining of PRL-3 was found in Dukes' A
      (0/26), Dukes' B (0/30), Dukes' C (18/30) and Duke's D (20/21) although the PRL-3
      expression could not predict metachronous liver metastasis (MLM) in Dukes' C
      patients. PRL-3 expression showed an inverse correlation of prognosis in a
      univariate prognostic analysis (P<0.0001), though a multivariate assay failed to
      demonstrate PRL-3 relevance as an independent prognostic factor. PRL-3 expression
      was closely associated with classic prognostic factors such as the pN factor
      (P<0.0001), H factor-synchronous liver metastasis (SLM) (P<0.0001), pT factor
      (P=0.0002), preoperative CEA (P<0.0001) and preoperative CA19-9 (P<0.0001).
      Multivariate logistic regression analysis of PRL-3 expression revealed that the
      pN factor (P<0.0001), CEA (P<0.0001) and CA19-9 (P<0.0001) were finally remnant
      as an independent association with PRL-3. However, the H factor (SLM) was
      eliminated. Our data suggested that liver metastasis by PRL-3 is putatively
      mediated through lymph node metastasis and elevated tumor markers in the serum
      and the PRL-3 expression may not represent a direct causative mechanism of liver
      metastasis.

PMID- 18813814
TI  - Deregulation of the G1/S phase transition in cancer and squamous intraepithelial
      lesions of the uterine cervix: a case control study.
AB  - High-risk types of HPV express the oncoproteins, E6 and E7, that can inactivate
      TP53 and RB1, respectively, and thus take control of both cell cycle and
      apoptosis. Herein, the mRNA expression profiles of 24 G1/S checkpoint genes were
      analysed in cancer and squamous intraepithelial lesions (SIL) of the uterine
      cervix. In total 35 squamous cervical carcinomas, 26 high-grade SIL (HSIL), 33
      low-grade SIL (LSIL) tissues, and 28 normal uterine cervix specimens as controls
      were assessed by RT-PCR. Five genes were found to be upregulated only in tumours,
      RBL2, E2F2, CDK6, CCNE1 and MYC; eight in tumours and HSILs, E2F1, E2F3, E2F5,
      CCND1, CDK2, CDKN1B, PCNA and POLA, and five in tumours, HSILs and LSILs, TP53,
      E2F4, CDKN1A, CDKN2A and DHFR. MDM2 was found to be upregulated in SIL, while
      RBL1 was found to be downregulated in all three groups of cases. TP73 exhibited
      lower levels in carcinomas; however, its exon 13-containing isoforms were
      increased and exon 2-containing isoforms were reduced in both cancer and HSIL.
      Three genes, RB1, CDK4 and CDKN2D, did not exhibit any significant alteration in
      gene expression. Hierarchical clustering revealed that this set of G1/S
      checkpoint genes was able to discriminate the total 122 samples into groups of
      disease and non-disease with only 8 exceptions (6.6%). Our data suggest that
      deregulation of G1/S phase transition in cervical carcinogenesis is a progressive
      process. Certain clusters of genes are activated very early in pre-cancerous SILs
      while others are activated later, during malignant transformation. The ability of
      this array of markers to identify disease status suggests that it could be used
      for diagnostic purposes.

PMID- 18813813
TI  - Evaluation of the lateral sentinel node by indocyanine green for rectal cancer
      based on micrometastasis determined by reverse transcriptase-polymerase chain
      reaction.
AB  - The significance of dissecting the lateral pelvic lymph node (LN) for lower
      rectal cancer remains controversial. We detected the lateral sentinel node (SN)
      by indocyanine green (ICG) and micrometastases using carcinoembryonic antigen
      (CEA)-specific reverse transcriptase-polymerase chain reaction (RT-PCR). Twenty
      five patients who underwent curative surgery with a dissection of the lateral
      pelvic LNs between 2003 and 2005 were examined. We investigated the existence of
      lateral SNs and any associations between pathological metastases and
      micrometastases by RT-PCR. Lateral SNs were detected in 7 (28%) of the 25
      patients. The number of lateral SNs was 13 LNs, or 1.9 nodes per case. Of the 25
      cases, 7 had lateral LN metastases based on pathological examinations in
      dissected lateral LNs. Three cases had massive lateral LN swelling by pre
      operative pelvic CT and the SNs were not detected in them. The SNs were detected
      in two cases and were negative based on pathological examinations and positive
      according to a genetic diagnosis. SNs were detected in one case, which was
      positive based on pathological examinations and a genetic diagnosis. SN was not
      detected in one case. There were five SNs in which CEA was positive by RT-PCR,
      though only one of them was positive based on pathological examinations. No SNs
      were observed that were negative based on a genetic diagnosis, but were positive
      according to the pathological diagnosis. We detected the lateral SNs using ICG.
      The sensitivity of identifying lateral LN metastasis was improved by the use of a
      genetic diagnosis. However, the detection rate was still low, therefore we need
      to develop a new method for detecting SNs.

PMID- 18813815
TI  - Relation between serum levels of cell-free DNA and inflammation status in
      hepatitis C virus-related hepatocellular carcinoma.
AB  - Our study revealed that the level of circulating cell-free DNA (cfDNA) is
      increased in the serum of patients with hepatitis C virus (HCV)-related
      hepatocellular carcinoma (HCC). To gain insight into the mechanism underlying
      this phenomenon, we examined the association between cfDNA levels and various
      clinicopathological factors in 96 patients with HCV-related HCC and 99 non-HCC
      patients with HCV. Using pooled DNA microarray data, we profiled the expression
      patterns of inflammatory cytokine genes in 14 primary tumors from the group of
      HCC patients. We found that there were positive associations between the cfDNA
      level, aspartate aminotransferase levels and the number of leukocytes and
      neutrophils in patients with HCV-related HCC but not in non-HCC patients with
      HCV. The serum cfDNA level was not associated with other clinicopathological
      factors in HCC or non-HCC patients. A cluster analysis based on the inflammatory
      cytokine gene data revealed that HCCs with a high serum cfDNA level had increased
      levels of several inflammatory cytokine genes, suggesting that the serum cfDNA
      level is associated with the inflammatory status in primary tumors in HCV-related
      HCC.

PMID- 18813816
TI  - Lack of modifying potential of 8-methoxypsoralen in the promotion or progression
      stages of lung carcinogenesis in A/J female mice.
AB  - Pretreatment with 8-methoxypsoralen (8-MOP), a potent human CYP2A6 inhibitor,
      strongly suppresses lung tumorigenesis by 4-(methylnitrosamino)-1-(3-pyridyl)-1
      butanone (NNK) in female A/J mice. Since it has been reported that CYP2A protein
      is highly expressed in NNK-induced lung adenomas and adenocarcinomas, potential
      anticancer properties of 8-MOP in female A/J mice were examined subsequent to
      initiation. The agent was administered at 100 ppm levels in the diet during the
      promotion phase (experimental weeks 1-16) and progression phase (experimental
      weeks 16-32) and mice were sacrificed for histopathological examination of lung
      tumor development at 16 and 32 weeks after the initiation of NNK treatment (2
      mg/0.1 ml saline/mouse, i.p.), respectively. Chemopreventive effects of 8-MOP
      were not observed in either experiment. In addition, no modifying effects on
      hepatic mRNA levels for CYP2A5, considered to be the mouse ortholog of human
      CYP2A6, were evident. On immunohistochemical analysis, the CYP2A protein was
      found to be overexpressed in all lung adenomas and adenocarcinomas, with or
      without 8-MOP. It can be concluded from the present data that 8-MOP at 100 ppm in
      the diet does not prevent mouse lung carcinogenesis when administered in the post
      initiation phase.

PMID- 18813817
TI  - An unusual p53 mutation detected in Burkitt's lymphoma: 30 bp duplication.
AB  - Burkitt's lymphomas (BL) are aggressive rapidly growing tumors typified by a high
      c-myc expression resulting from t(8;14)(q24;q32), t(2;8)(p12;q24) or
      t(8;22)(q24;q11) translocations. Alterations of the p53 tumor suppressor are also
      relatively frequent in BL. Several approaches have been adopted for detection of
      the p53 aberrations such as immunohistochemical analyses, immunoblotting, DNA
      sequencing, fluorescence in situ hybridization (FISH), and functional assays. We
      used these methods to characterize the p53 mutation in tumor cells of a 53-year
      old male suffering from Burkitt's lymphoma. By immunohistochemical analyses, we
      detected high levels of the p53 protein in the tumor tissue. Immunoblotting
      showed a higher molecular weight of the p53 protein overexpressed in the tumor
      tissues than that of the standard p53 protein. Similarly, the molecular weight of
      the PCR product prepared by amplification of the tumor p53 cDNA was higher than
      that of the standard p53 cDNA. Functional analyses of separated alleles in yeast
      evidently revealed that the tumor p53 protein was transcriptionally non
      functional. The yeast colonies expressing this p53 variant possessed a unique
      phenotype in that they were red with many white spots on their surface.
      Sequencing of the tumor cDNA revealed a duplication of the 30 bp region of the
      p53 gene (g.12155_12184dup30) leading to a repeat of 10 amino acids (Pro-77 to
      Ala-86) in the p53 protein. Further analyses showed that the mutation was
      unstable in yeast cells. The FISH analyses did not confer loss of the p53
      specific locus 17p13.

PMID- 18813818
TI  - Serosal penetration is an important prognostic factor for gastrointestinal
      stromal tumors.
AB  - Predicting the malignant potential of gastrointestinal stromal tumors (GISTs)
      remains difficult. We assessed the value of serosal penetration, an established
      prognostic factor in solid tumors, to determine the clinical outcome in patients
      with GISTs. From 1996-2002, 25 consecutive patients with GIST underwent surgical
      resection at our Department. The histopathological presence of serosal
      penetration was assessed to predict clinical outcome. In addition, the
      established histopathological classification system by Franquemont (modified by
      using the Ki-67 proliferation index), was applied to each study patient. A Ki-67
      index > or =5% (p<0.001) and a mitotic rate > or =5/50 high-power fields
      (p<0.047) significantly correlated with a shorter survival, whereas a tumor size
      >5 cm (p=0.07) tended towards a worse prognosis. The survival of patient groups
      defined by Franquemont (p=0.03) were of prognostic relevance. The presence of
      serosal penetration significantly correlated (p<0.01) with a shorter survival.
      Our data suggest that the presence of serosal penetration is a negative
      prognostic factor for GISTs. Serosal penetration may become a useful additional
      parameter for the classification of the malignant potential of GISTs. Since our
      data are merely hypothesis-generating, serosal penetration should be evaluated in
      large prospective databases.

PMID- 18813819
TI  - Piplartine induces caspase-mediated apoptosis in PC-3 human prostate cancer
      cells.
AB  - The present study examined the anti-proliferative effects of piplartine on the
      human prostate cancer cell line PC-3. This is the first report demonstrating the
      piplartine anti-cancer activity toward prostate cancer cell lines, although its
      precise mechanism of action is still not completely defined. In MTT assays, it
      preferentially inhibited growth of androgen-independent PC-3 cells in a dose
      dependent (3-30 microM) and time-dependent (12-48 h) manner. In PC-3 cells, it
      showed an IC50 of 15 microM after 24 h of treatment. After a 24-30 microM
      treatment for 24 h, there were some reduction of cell volume, cell vacuolization,
      chromatin condensation and increased number of apoptotic cells visible by light
      and fluorescence microscopy. Agarose gel electrophoresis revealed that cells
      treated with piplartine exhibited DNA fragmentation. In addition, growth
      inhibition of PC-3 cells was associated with G2/M arrest and sub-G1 accumulation.
      Higher concentrations (24-30 microM) of piplartine modulated apoptosis-related
      protein expression by down-regulating cdc-2 expression and up-regulating
      PARP/procaspase-3 cleavage. Also, PC-3 cells treated with piplartine demonstrated
      caspase-3 activation, as observed with an in vitro caspase-3 colorimetric assay
      kit. Taken together, these results demonstrated that high concentrations of
      piplartine exhibited anti-proliferative and anti-cancer effects on PC-3 cells and
      that caspase-3-mediated PARP cleavage and cell cycle arrest at G2/M phase are
      involved in the underlying cellular mechanism of the apoptosis process.

PMID- 18813820
TI  - Modulation of intestinal environment by prebiotic germinated barley foodstuff
      prevents chemo-induced colonic carcinogenesis in rats.
AB  - Butyrate was shown to have a preventive effect on colon cancer in vivo.
      Germinated barley foodstuff (GBF) was in a prebiotic stage and had the potency to
      attenuate mucosal inflammation and to increase fecal butyrate production in
      colitis. This study aimed to determine whether the GBF treatment in a colon
      cancer model had the potency to suppress colon cancer. After a pre-feeding of
      either a control or a GBF diet for two weeks, male F344 rats received
      subcutaneous injections of azoxymethane twice, at a dose level of 15 mg/kg body
      weight. The injections were administered once a week for 2 weeks (n=10/group).
      Four weeks after that, the number of aberrant crypt foci (ACF) and heat shock
      protein (HSP) 25-positive cells in colonic mucosa were observed histologically.
      The mRNA level of slc5a8 was evaluated by in situ hybridization. Colonic mucosal
      beta-catenin was determined by Western blotting. Cecal short chain fatty acids,
      beta-glucosidase and beta-glucuronidase were also determined. The results showed
      that GBF treatment significantly decreased the number of ACF and beta-catenin
      formations in the colonic mucosa. GBF significantly increased the production of
      slc5a8, which is a tumor suppressor gene, as well as the cecal butyrate content
      and beta-glucosidase activity. beta-glucuronidase activity remained at the same
      level in GBF and control subjects. The number of HSP25-positive cells in GBF was
      higher than that in the control group, although it did not reach significant
      difference. In conclusion, GBF showed anti-tumorigenicity in the AOM rat model.
      Changes in the colonic environment featured through the increase of butyrate
      production were found. Although a more detailed study is required, this study
      showed the promising anti-neoplastic effects of prebiotic treatment.

PMID- 18813821
TI  - Effect of hypoxia and re-oxygenation on cell invasion and adhesion in human
      ovarian carcinoma cells.
AB  - Hypoxia inducible factor 1alpha (HIF-1alpha) regulates the transcription of a
      number of genes under hypoxia and other extracellular or intracellular
      stimulations. It also promotes angiogenesis, tumor metastasis and invasion. To
      investigate the effect of hypoxia and reoxygenation on cell proliferation,
      invasion and adhesion, which are all related to ovarian cancer, we applied
      chemically-induced hypoxia in the cultured human ovarian carcinoma cell line, HO
      8910PM. Semi-quantitative RT-PCR results show that CoCl2 induces the expression
      of HIF-1alpha in a time- and dose-dependent manner. MTT assay results show that
      CoCl2-induced hypoxia inhibits cell proliferation which is recovered by
      reoxygenation. The Boyden and cell adhesion test results indicate that CoCl2
      induced hypoxia inhibits cell invasion and adhesion which are markedly enhanced
      by reoxygenation in the human ovarian carcinoma cell line, HO-8910PM.
      Collectively, our data provide insight into understanding molecular mechanisms of
      the invasiveness of ovarian cancer under the conditions of hypoxia and
      reoxygenation.

PMID- 18813822
TI  - Suppression of growth and hepatic metastasis of murine B16FO melanoma cells by a
      novel nutrient mixture.
AB  - Highly metastatic melanoma is resistant to existing therapies. Our main objective
      was to investigate the effect of a nutrient mixture (NM) on B16FO tumor growth
      and hepatic metastasis. Tumor growth was studied in athymic nude male mice, 5-6
      weeks old, inoculated with 10(6) B16FO melanoma cells subcutaneously and fed
      either a regular diet or one supplemented with 0.5% NM. Four weeks later, the
      mice were sacrificed and their tumors excised, weighed and processed for
      histology. Metastasis was studied in C57BL/6 mice, which received 10(6) B16FO
      melanoma cells by intrasplenic injection, as well as a regular or 0.5% NM
      supplemented diet for 2 weeks. Survival was studied in C57BL/6 mice receiving
      10(6) B16FO melanoma cells intraperitoneally (i.p.) followed by the regular, NM
      supplemented, or regular diet in addition to being administered with 2 mg NM
      injection 3 times per week. NM inhibited the growth of B16FO melanoma cells by
      50%. Lesions in the two groups were consistent with malignant melanoma. Mice were
      injected with B16FO cells in the spleen. Those fed the regular diet developed
      large black spleens and livers indicating growth in the spleen and metastasis to
      the liver. In contrast, mice supplemented with NM showed less growth in spleen,
      but also reduced metastasis to the liver. The survival time of mice receiving NM
      supplementation and B16FO cells i.p. was greater than in mice which were fed the
      regular diet. To confirm effects in vivo, we investigated the effect of NM on
      murine B16FO melanoma cells in vitro, including cell proliferation by MTT assay,
      morphology by hematoxylin and eosin (H&E) staining and apoptosis using live green
      caspase detection kit. In vitro, NM was not toxic at 100 microg/ml concentration,
      but exhibited 44% toxicity over the control at 500 and 1000 microg/ml. H&E did
      not indicate any changes up to 100 microg/ml. NM induced slight apoptosis at 100
      microg/ml, moderate at 500 and extensive at 1000 microg/ml concentration.

PMID- 18813823
TI  - Yanhusuo extract inhibits metastasis of breast cancer cells by modulating mitogen
      activated protein kinase signaling pathways.
AB  - Yanhusuo (Corydalis yanhusuo W.T. Wang) is a well-known traditional Chinese
      medicine (TCM). In this study, we attempted to characterize in detail the
      signaling cascades that produce its anti-metastatic effect on the human breast
      cancer cell line, MDA-MB-231. We found that the yanhusuo extract inhibited the
      migration and invasion of MDA-MB-231 cells in vitro. In addition, the yanhusuo
      extract inhibited the mRNA expression and activity of metalloproteinase-9 (MMP
      9). The anti-cancer metastasis effect of yanhusuo involved the activation of p38
      and inhibition of ERK1/2 and SAPK/JNK mitogen-activated protein kinase (MAPK)
      signaling. Our experiments identified the biological activity of yanhusuo against
      cancer metastasis in vitro and provide a rationale for its further investigation.

PMID- 18813824
TI  - Chromosomal aberrations in head and neck squamous cell carcinomas in Norwegian
      and Sudanese populations by array comparative genomic hybridization.
AB  - We used microarray-based comparative genomic hybridization to explore genome-wide
      profiles of chromosomal aberrations in 26 samples of head and neck cancers
      compared to their pair-wise normal controls. The samples were obtained from
      Sudanese (n=11) and Norwegian (n=15) patients. The findings were correlated with
      clinicopathological variables. We identified the amplification of 41 common
      chromosomal regions (harboring 149 candidate genes) and the deletion of 22 (28
      candidate genes). Predominant chromosomal alterations that were observed included
      high-level amplification at 1q21 (harboring the S100A gene family) and 11q22
      (including several MMP family members). Regions of copy number increase was also
      identified at 6p21 (p21), 7p12 (EGFR), 17p13 (p53) and 19p13.2 (p19INK4d), while
      regions showing deletion included among others 3p25.2 (RAF1) and 9p21 (p15, p16).
      We found genes from four common biological pathways (MAPK signaling, cytokine
      cytokine receptor interaction, ECM-receptor interaction and Jak-STAT signaling)
      to be predominantly over-represented in areas of gain and loss. The current study
      provides valuable information on chromosomal aberrations likely to be involved in
      the pathogenesis of head and neck cancers. An increased copy number of the S100A
      and MMP gene family members, known to be involved in invasion and metastasis, may
      play an important role in the development of the tumors. Hierarchical clustering
      of the chromosomal alterations with clinicopathological parameters showed little
      correlation, suggesting an occurrence of gains/losses regardless of ethnic
      differences and clinicopathological status between the patients from the two
      countries. Our findings indicate the existence of common gene-specific
      amplifications/deletions in these tumors, regardless of the source of the samples
      or attributed carcinogenic risk factors.

PMID- 18813825
TI  - Co-expression of receptor tyrosine kinases in esophageal adenocarcinoma and
      squamous cell cancer.
AB  - This study aimed to define the co-expression pattern of target receptor tyrosine
      kinases (RTKs) in human esophageal adenocarcinoma and squamous cell cancer. The
      co-expression pattern of vascular endothelial growth factor receptor (VEGFR)1-3,
      platelet-derived growth factor receptor (PDGFR)alpha/beta and epidermal growth
      factor receptor 1 (EGFR1) was analyzed by RT-PCR in 50 human esophageal cancers
      (35 adenocarcinomas and 15 squamous cell cancers). In addition, IHC staining was
      applied for the confirmation of the expression and analysis of RTK localisation.
      The adenocarcinoma samples revealed VEGFR1 (97%), VEGFR2 (94%), VEGFR3 (77%),
      PDGFRalpha (91%), PDGFRbeta (85%) and EGFR1 (97%) expression at different
      intensities. Ninety-four percent of the esophageal adenocarcinomas expressed at
      least four out of six RTKs. Similarly, squamous cell cancers revealed VEGFR1
      (100%), VEGFR2 (100%), VEGFR3 (53%), PDGFRalpha (100%), PDGFRbeta (87%) and EGFR1
      (100%) expression at different intensities. All esophageal squamous cell
      carcinomas expressed at least four out of six RTKs. While VEGFR1-3 and PDGFRalpha
      and EGFR1 was expressed by tumor cells, PDGFRbeta was restricted to stromal
      cells, which also depicted a PDGFRalpha expression. Our results revealed a high
      rate of RTK co-expression in esophageal adenocarcinoma and squamous cell cancer
      and may encourage application of multi-target RTK inhibitors within a multimodal
      concept as a promising novel approach for innovative treatment strategies.

PMID- 18813826
TI  - Expression of EGFR and follicular dendritic markers in lymphoid follicles from
      patients with Castleman's disease.
AB  - This study investigated the useful morphologic and immunophenotypic findings for
      the diagnosis of Castleman's disease (CD). We focused on the distribution and
      expression of follicular dendritic cells (FDC) in lymphoid follicles from
      patients with CD. Eleven CD cases of the hyaline vascular (HV) variant and six
      cases of the plasma cell (PC) variant were studied using tissue microarray and
      paraffin resistant monoclonal antibodies CD21, CD35, and EGFR, a new novel marker
      of FDC, as well as an antibody against human herpes virus 8 (HHV8). Epstein-Barr
      virus (EBV) was detected by means of in situ hybridization with a fluorescein
      isothiocyanate-labeled EBV-encoded RNA (EBER) specific oligonucleotide. The FDC
      network of the PC variant (n=4) was similar to that seen in normal or reactive
      germinal centers. In contrast, all HV variants and 2 cases of the PC variant were
      either expanded, disrupted, or exhibited multiple tight collections of FDC both
      in germinal centers and in mantle zone lymphocytes. The expanded mantle zone
      lymphocytes were CD20+, Bcl2+, PAX5+, and MUM1- with less number of CD3+ T cells
      admixed. Other features of the HV variant included follicular regression and
      vascular ingrowth of the germinal centers, whereas features of the PC variant
      were follicular hyperplasia and interfollicular plasmacytosis. In addition, EBV
      infection was positive in three CD cases, and one case had co-expression of HHV8
      and EBV infection. Taken together, we found immunophenotypic differences of
      mantle zone lymphocytes and FDC network patterns of lymphoid follicles in CD.
      Thus, we conclude that these differences are relevant for the differential
      diagnosis of the two histopathologic variants of CD.

PMID- 18813827
TI  - The additional value of integrated PET/CT over PET in initial lymph node staging
      of esophageal cancer.
AB  - The purpose of the present study was to assess the contribution of simultaneous
      functional/anatomical imaging using integrated 18F-fluorodeoxyglucose-positron
      emission tomography/computed tomography (FDG-PET/CT), compared with PET alone for
      the evaluation of initial lymph node staging in esophageal cancer. We studied 167
      consecutive patients with thoracic esophageal squamous cell carcinoma (SCC) who
      had radical esophagectomy performed between January 1999 and April 2007. For
      individual nodal group evaluation, PET/CT showed 46.0% sensitivity (p<0.05 vs.
      PET), 99.4% specificity, 95.1% accuracy (p<0.05 vs. PET), 87.0% positive and
      95.5% negative predictive values. PET showed 32.9% sensitivity, 98.9%
      specificity, 93.1% accuracy, 74.7% positive predictive value and 93.9% negative
      predictive value. Thus, the sensitivity and accuracy of PET/CT were significantly
      higher than those of PET. Comparisons between CT, PET and PET/CT in detecting
      lymph node metastasis by each region showed that PET/CT had a higher sensitivity
      in lower thoracic regions than PET and CT (p<0.05 vs. CT and PET). Lymph node
      staging (N0 vs. N1) was not significantly different, but staging per lymph nodal
      group was significantly better with PET/CT. Integrated PET/CT imaging with co
      registration of anatomic and functional imaging data is useful in the initial
      lymph node staging of patients with operable esophageal cancer compared with PET
      alone.

PMID- 18813828
TI  - The growth inhibition of hepatocellular and cholangiocellular carcinoma cells by
      gemcitabine and the roles of extracellular signal-regulated and checkpoint
      kinases.
AB  - We examined the effects of gemcitabine, a pyrimidine analogue, on hepatocellular
      carcinoma (HCC) and cholangiocellular carcinoma (CCC) cells. After HCC cells
      (HepG2, Hep3B, HLF and PLC/PRF/5) and CCC cells (HuCCT-1) were treated with
      gemcitabine, cellular growth, cell cycle, nuclear morphology and activity of
      signaling molecules were evaluated by WST-8 assays, flow cytometry analysis,
      Hoechst 33258 staining and Western blotting, respectively. We found that
      gemcitabine significantly inhibited the growth of HCC and CCC cells in a dose-
      and time-dependent manner. Gemcitabine induced cell cycle arrest at the G1 phase,
      however, the sub-G1 fraction was not observed and nuclear morphology did not
      indicate the induction of apoptosis. Gemcitabine induced differential activation
      of checkpoint kinases, Chk2 and Chk1, in HCC and CCC cells, respectively and
      gemcitabine activated extracellular signal-regulated kinase (ERK)1/2 in both cell
      types. After the cells were pretreated with a MEK inhibitor U0126, activations of
      these checkpoint kinases were abrogated and the cell death was enhanced. These
      results demonstrate that gemcitabine inhibited the growth of HCC and CCC cells by
      cell cycle arrest without apoptosis and that the ERK/Chk1/2 signaling pathway was
      in part responsible for the resistance to gemcitabine. Our findings shed light on
      treating patients with HCC and CCC by gemcitabine, especially when combined with
      a MEK inhibitor and Chk1/2 inhibitors.

PMID- 18813829
TI  - Stat3 as a molecular target in RNA interference-based treatment of oral squamous
      cell carcinoma.
AB  - Constitutive activation of signal transducer and activator of transcription 3
      (Stat3) has been observed in many human malignancies. Using the sequence-specific
      RNA interference (RNAi) method to switch off Stat3 expression, it may be possible
      to arrest cancer growth. In this study, we aimed to identify the most effective
      sequence of a synthetic small interfering RNA (siRNA) specific for Stat3 (Stat3
      siRNA) and the effect of Stat3 suppression on the growth of oral squamous cell
      carcinoma cells. Ten designed siRNAs with known sequences were screened for the
      best RNAi effect at the working concentrations of 1 and 10 nM. The range of
      reduction of Stat3 expression varied from 21 to 67% for 10 nM siRNAs, and from 13
      to 73% for 1 nM siRNAs. Three out of the 10 screened siRNAs reduced Stat3
      expression to lower levels compared with the GFP-siRNA control. The interferon
      response of some siRNAs was observed at a concentration of 10 nM. However, at 1
      nM, the mRNA levels of interferon response genes (OAS1, OAS2, MX1 and ISFG3gamma)
      remained unchanged. The growth of GFP-SAS, HSC-3, HSC-4 and KB cells was strongly
      inhibited by the use of three effective Stat3-siRNAs in comparison with other
      Stat3-siRNAs and GFP-siRNA. Moreover, the mRNA levels of genes for which
      transcription is activated by Stat3 were markedly suppressed. These results
      suggest that targeting Stat3 using siRNA may constitute a useful approach for the
      treatment of oral squamous cell carcinoma.

PMID- 18813830
TI  - Comparison of cisplatin-paclitaxel combination versus cisplatin-etoposide in
      patients with small-cell lung cancer: a Phase III study.
AB  - Cisplatin-paclitaxel and cisplatin-etoposide combination therapies were compared
      in limited and extensive disease in patients with small-cell lung cancer. The
      primary objectives were to determine median and overall survival, time to tumor
      progression and tolerance and the secondary objective, the response rate. From
      January 2003 till July 2007, 108 patients were enrolled in the study. All
      patients had histologically- or cytologically-confirmed small-cell lung cancer.
      All patients were chemotherapy and radiotherapy naive. The patients were
      designated to receive six cycles: in the investigational Arm A, cisplatin, 80
      mg/m(2) and paclitaxel 175 mg/m(2) were infused on day 1 (1 cycle) and repeated
      every 3 weeks. In the control Arm B, cisplatin, 80 mg/m(2) was administered on
      day 1 and etoposide, 120 mg/m(2) per day was given on days 1-3 (1 cycle), every 3
      weeks. In Arm A, 6 (11.3%) patients achieved a complete response and 32 (58.1%),
      a partial response; in Arm B, 7 (12.7%) patients achieved a complete response and
      32 (58.2%) a partial response. The median survival time in Arm A patients was 12
      months and in Arm B, 13 months, p=0.354. The time to tumor progression (TTP) was
      8 and 6 months for Arms A and B, respectively (p=0.060). Toxicity, although
      common in both Arms, was acceptable. Neutropenia, anemia and diarrhea were higher
      in the control Arm. The cisplatin-paclitaxel combination is not superior to
      cisplatin-etoposide with respect to survival, TTP, toxicity and response rate.
      The former combination could be applied as an alternative chemotherapy regimen
      for patients with limited or advanced small-cell lung cancer.

PMID- 18813831
TI  - Inhibition of system L (LAT1/CD98hc) reduces the growth of cultured human breast
      cancer cells.
AB  - It has been suggested that system L (LAT1/CD98hc) is up-regulated in cancer
      cells, including breast tumour cells, and is therefore a promising molecular
      target to inhibit or limit tumour cell growth. In view of this, we have examined
      the effect of BCH and other inhibitors of system L on the growth of MCF-7, ZR-75
      1 and MDA-MB-231 cells. Treating cells with BCH markedly inhibited the metabolism
      of WST-1 in a dose-dependent fashion. Similarly, melphalan and D-leucine
      inhibited the growth of cultured breast cancer cells whereas MeAIB, an inhibitor
      of system A, was without effect. The effects of BCH and melphalan on cell growth
      were non-additive suggesting that both compounds were acting at a single locus.
      The results indicate that system L is required to maintain MCF-7, ZR-75-1 and MDA
      MB-231 cell growth and support the notion that LAT1/CD98hc may be a suitable
      target to inhibit breast cancer progression.

PMID- 18813832
TI  - Docetaxel chemotherapy for metastatic hormone refractory prostate cancer as first
      line palliative chemotherapy and subsequent re-treatment: Birmingham experience.
AB  - Three-weekly docetaxel chemotherapy with prednisolone is now considered standard
      of care for patients with metastatic hormone refractory prostate cancer (MHRPC).
      This study reports the efficacy and toxicity of first-line docetaxel chemotherapy
      followed subsequently by re-treatment on biochemical disease progression (BDP).
      Forty-two patients with MHRPC were treated with three-weekly docetaxel
      chemotherapy 75 mg/m(2) and 10 mg of prednisolone daily. Median age 73 years
      (range 58-87) and median initial PSA 182 ng/ml (range 19.9-1500). Of these
      patients, 10 were re-treated with the same regimen (second-line chemotherapy) on
      BDP. A further 3 out of these 10 patients received 2nd re-treatment (third-line
      chemotherapy) with docetaxel chemotherapy on BDP. Fifty-four percent of patients
      responded to first-line docetaxel chemotherapy and all re-treated patients
      responded again with a PSA reduction >50%. Median treatment-free interval prior
      to second and third-line chemotherapy was 24 and 26 weeks, respectively. Grade 3
      or 4 neutropenia occurred in 2.5, 7 and 12% of the total number of cycles in
      patients receiving first-, second- and third-line docetaxel chemotherapy,
      respectively. Median survival was 13 months (range 3-35) and one-year overall
      survival 52%. This is the first report of three-weekly docetaxel chemotherapy re
      treatment in patients with MHRPC and demonstrates that patients who initially
      respond to docetaxel chemotherapy maintain their sensitivity to subsequent re
      treatment without a significant rise in haematological toxicity.

PMID- 18813833
TI  - Presence and enzymatic activity of prostate-specific antigen in archival prostate
      cancer samples.
AB  - Patients with advanced prostate cancer frequently have a poor prognosis as a
      result of metastasis. The serum prostate-specific antigen (PSA) test is widely
      used for the diagnosis of prostate cancer. The enzymatic activity of PSA may be
      involved in the invasion of prostate cancer. We set out to determine the
      prevalent form of PSA in human prostate adenocarcinoma samples by ELISA and
      Western blot analysis and its enzymatic activity using a synthetic substrate S
      2586 and fibronectin. Our results show that in serum from prostate cancer
      patients and in tumour homogenates, the prevalent form was PSA bound to alpha1
      antichymotrypsin. All homogenates showed enzymatic activity towards a synthetic
      PSA substrate, whereas only five samples showed activity at 28 kDa towards
      fibronectin as determined by enzymography, which is most likely due to active
      PSA. Human prostate cancer LNCaP cells produced largely inactive PSA. In
      comparison, 22Rv1 cells produced 29-fold less PSA, but with high specific
      activity. Similarly, our results from the human prostate cancer tissue samples
      also show that free PSA appears to exist in diverse forms of very different
      specific activity. Since PSA, as a serine protease, may be involved in the
      invasion of prostate cancer, our results suggest that prostate cancers have
      potentially diverse invasive capacity due to differences in specific enzymatic
      activity of PSA.

PMID- 18813834
TI  - Hepatocellular carcinoma-related gene targeting using the large circular
      antisense library.
AB  - The large circular (LC)-antisense library to the 221 unigene clone was
      constructed and utilized in the identification of genes functionally involved in
      the growth of hepatocellular carcinoma cells. We identified that 37 out of the
      221 members of the antisense library exerted a marked inhibitory effect on the
      growth of Huh-7. The putative functional categorization of each gene was then
      conducted on the basis of the sequence information. The relative expression
      levels of target genes were measured and treated with two LC-antisense molecules
      by real-time PCR. LC-antisense to EIF3EIP and AFP abolished the expression of
      EIF3EIP and AFP to the level of approximately 7 and 39% compared to the control
      treatment in Huh-7 cells, respectively. LC-antisense molecules to EIF3EIP and AFP
      were simultaneously treated with 5-FU to Huh-7 cells. Two LC-antisense molecules
      showed additive effects with 5-FU compared with 5-FU alone, respectively. The
      combination of LC-antisense molecules and 5-FU showed a dramatic increase of sub
      G1 apoptotic cell death fraction in cell cycle analysis, respectively. Therefore,
      these candidates may be used as target genes for drug development or adjuvant of
      conventional chemotherapeutic drugs.

PMID- 18813835
TI  - Aneuploidy and high S-phase as biomarkers of poor clinical outcome in poorly
      differentiated and anaplastic thyroid carcinoma.
AB  - This study aimed to investigate the prognostic influence of DNA flow cytometry
      and RAS gene mutations in patients with poorly differentiated (PDTC) and
      anaplastic thyroid carcinoma (ATC). The series consisted of 26 patients with PDTC
      and ATC, and a median follow-up of 10 months (range 1-138). DNA ploidy and S
      phase fraction (SPF) were assessed by flow cytometry on frozen samples. RAS point
      mutations were detected using PCR techniques. Disease staging and tumour
      angioinvasion were included as prognostic parameters for survival analysis.
      Nineteen patients (73.1%) succumbed to the disease (median time 5 months; range 1
      45). Eighteen tumours (69.2%) were classified as DNA aneuploid. Median SPF was
      5.6% (range 1.9-23.1), which was used as a cut-off value to distinguish between
      low versus high cell proliferation. Three of 20 (15%) patients presented N-RAS
      gene mutations in codon 61. DNA aneuploidy was most frequently found in female
      patients (p=0.034). Kaplan-Meier and Cox regression analyses showed that only DNA
      aneuploidy (p=0.044 and p=0.055, respectively) and high SPF (p=0.001 and p=0.006,
      respectively) significantly correlated with worse survival. The results indicate
      that aneuploidy and high SPF are biomarkers of poor clinical outcome in PDTC and
      ATC, which may provide useful prognostic information with a potentially
      therapeutic impact in patient management.

PMID- 18813836
TI  - DNA methylotype analysis in colorectal cancer.
AB  - The methylation status of a gene promoter is considered to be an important
      mechanism for the development of many tumors, including colorectal cancer. Recent
      studies have shown that specific patterns of DNA methylation across multiple CpG
      loci in some human tumors are more informative than the detection of one single
      CpG locus in tumor genomes. In the present study, multiple CpG methylations of
      three genes (CDKN2A, DPYD and MLH1) were detected in DNA samples from patients
      with colorectal cancer using Pyrosequencing(R) technology. The bisulfite
      converted DNA was amplified with a nested PCR and five or six CpG loci of each
      gene were assessed to determine DNA methylotype. Our data showed that 10/49
      (20.4%), 6/48 (12.5%) and 14/49 (28.6%) of tumors were methylated with a DNA
      methylation level >0.2 in CDKN2A, DPYD and MLH1, respectively. Our study
      indicated a similar DNA methylation level across the multiple CpG loci for all
      three genes in the methylated tumor DNA samples, demonstrating a dichotomous
      trait in DNA methylation. The tumor DNA samples had unique DNA methylation
      patterns, which were high-degree and multiple-site methylation, but the normal
      DNA samples had no or a low-degree and dispersed single-site methylation. In
      addition, an inverse correlation in those methylated tumors was observed between
      DNA methylation and RNA expression for MLH1 (RS=-0.62, P=0.003), but not for
      CDKN2A and DPYD. In conclusion, distinctive DNA methylotypes exist in colorectal
      cancer and may depict a distinct biology in apparently homogeneous tumors.

PMID- 18813837
TI  - Positive regulation of migration and invasion by vasodilator-stimulated
      phosphoprotein via Rac1 pathway in human breast cancer cells.
AB  - This study aimed to investigate the role of the cytoskeleton-associated protein
      vasodilator-stimulated phosphoprotein (VASP) on the migration and invasion of
      human breast cancer cells and its relationship to Rac1 which is a member of the
      Rho family and has been found to be implicated in tumorigenesis, invasion and
      metastasis. We detected the mRNA and protein expression levels of VASP and Rac1
      of the non-invasive breast cancer cell line MCF-7 as well as the invasive cell
      line MDA-MB-231 by RT-PCR and Western blotting. GST pull-down assay was used to
      examine the activity of Rac1. Accordingly, the cell invasive migration ability
      was analyzed in a wound-healing assay (2D) and transwell assays (3D migration and
      invasion). We then used VASP-siRNA to inhibit the expression of VASP in breast
      cancer cells in order to study the relationship between the VASP expression level
      and the invasive migration ability of breast cancer cells. Rac1-siRNA was used to
      decrease the expression of Rac1, and observe its effect on the VASP expression
      level together with the migration and invasion ability of MCF-7 and MDA-MB-231
      cells. Our results revealed that the invasive breast cancer cell line MDA-MB-231
      showed a higher Rac1 activity and VASP expression level compared with the non
      invasive MCF-7. Inhibition of Rac1 or VASP by siRNA, respectively, decreased the
      migration and invasion ability of breast cancer cells and the transfection of
      Rac1 siRNA-mediated reduction of VASP expression at mRNA and protein levels.
      Collectively, our data showed that the higher expression level of VASP
      contributed to a higher invasive migration capacity of human breast cancer cells
      which was controlled by the Rac1 pathway.

PMID- 18813838
TI  - The influence of 1,25-dihydroxyvitamin D3 and 1,24-dihydroxyvitamin D3 on
      alphavbeta3 integrin expression in cancer cell lines.
AB  - Integrins are cell-surface receptors engaged in important cancer invasion
      processes, such as adhesion, migration, proliferation and differentiation. The
      aim of this study was to evaluate the effect of 1,25-dihydroxyvitamin D3
      (calcitriol) and its metabolite 1,24-dihydroxyvitamin D3 (PRI-2191) on
      alphavbeta3 integrin expression in various cancer cell lines. The expression
      levels of the beta3 and alphav integrins were reduced only in the WEHI-3 and LLC
      cell lines by the two compounds. Calcitriol or PRI-2191 treatment caused
      differentiation of WEHI-3 mouse leukemia cells, but apoptosis of LLC cells. WEHI
      3 and LLC cells exposed to calcitriol or PRI-2191 lost their migratory and
      adhesive potentials. The inhibition of migratory potential was higher in the LLC
      cells than in the WEHI-3 cells and appeared to correlate with the increased down
      regulation of alphavbeta3 integrin by calcitriol or PRI-2191. The observed in
      vivo effects (antitumor and antimetastatic) in mice bearing subcutaneously
      transplanted LLC cancer are possibly associated with inhibited migratory
      potential as a consequence of the lowered integrin expression caused by
      calcitriol or PRI-2191.

PMID- 18813839
TI  - Transformed follicular lymphoma: the 25-year experience of a UK provincial
      lymphoma treatment centre.
AB  - Follicular lymphoma can transform into diffuse large B cell lymphoma, which is
      usually associated with rapid disease progression, refractoriness to treatment
      and a poor outcome. We report the 25-year unselected experience of a UK
      provincial lymphoma treatment centre. This comprises of one of the largest series
      ever studied. Sixty-three patients were identified (56 initially presented as
      follicular lymphoma, 5 with 'transformed' lymphoma and 2 with follicular and
      transformed lymphoma from different biopsy sites). The median age at presentation
      was 54 years (range 32-76). The median time to transformation was 43 months
      (range 0-172). For all patients, the median overall survival was 76 months (range
      8-254) and from transformation 10 months (range 1-166); 46 of 63 patients have
      died. For those whose transformation was initially treated with CHOP chemotherapy
      10 were in complete remission (CR) and 14 were deceased (median survival 24,
      range 2-114 months). Five patients had high-dose chemotherapy and 3 were alive
      (at 25, 36 and 137 months). We conclude that CHOP chemotherapy (probably with
      rituximab) is a reasonable first treatment in fit patients and high dose
      chemotherapy with autologous stem cell support deserves further study.

PMID- 18813840
TI  - ERK2 CD domain mutation from a human cancer cell line enhanced anchorage
      independent cell growth and abnormality in Drosophila.
AB  - In a human cancer cell line, we previously found a mutation in codon 322 of the
      extracellular signal-regulated kinase (ERK2E322K), the protein showed a faster
      migration when compared to wild-type in SDS-PAGE and constitutive
      phosphorylation. However, the reason for the faster migration, and the
      biochemical and biological properties of the mutation is unknown. In this study,
      we report that the amino acid charge-change mutation in the common docking (CD)
      domain is important for fast migration. In vitro binding of ERK2E322K to MKP1 and
      RSK2 was lost, resulting in constitutive activation and possibly contributing to
      a more efficient colony formation in soft agar. We established transgenic flies
      by carrying the corresponding CD domain mutation, DERKE335K, which developed
      smaller and rougher eyes compared with the wild-type. Taken together, these data
      are consistent with ERK2E322K loss of contact with downstream effectors and its
      constitutive activation, presenting an oncogenic potential and weak abnormality
      in differentiation.

PMID- 18813841
TI  - Prediction of doxorubicin sensitivity in gastric cancers based on a set of novel
      markers.
AB  - Chemotherapy is the standard treatment for patients with advanced gastric cancer;
      however, it has been difficult to predict chemotherapy response. In the current
      study, we attempted to develop a prediction model for individual response to
      doxorubicin chemotherapy in gastric cancer patients based on the hypothesis that
      expression analysis of a set of key drug sensitivity genes for doxorubicin could
      allow us to predict therapeutic response. From literature and our previous
      microarray data, the genes correlative in the expression levels with doxorubicin
      response were chosen. We selected seven reliable prediction markers for
      doxorubicin from 90 candidate sequences. Using expression data of genes
      quantified by real-time reverse transcription-PCR in 20 specimens, we fixed a
      linear model by multiple regressions, which converted the quantified expression
      data into a calculated inhibition rate of doxorubicin. Using the same set of
      genes, we then validated the formula in an independent set of 19 specimens. Our
      results suggest that the response of gastric cancer to doxorubicin can be
      predicted by expression patterns in this set of genes. The response prediction
      model will be of practical use to evaluate patient before chemotherapy.

PMID- 18813842
TI  - Adiponectin mediates an antiproliferative response in human MDA-MB 231 breast
      cancer cells.
AB  - Numerous epidemiological studies have documented that obesity is a risk factor
      for breast cancer especially in post-menopausal women. However, the molecular
      basis of this association is not well known. In contrast to leptin, plasma levels
      of adiponectin, another major adipokine, are decreased in obese subjects.
      Therefore, we and others hypothesized that adiponectin may be a paracrine factor
      negatively controlling mammary tumor development. We recently demonstrated growth
      inhibition of the estrogen-sensitive breast cancer MCF-7 cell line by
      adiponectin. The purpose of the present study was to determine whether this anti
      proliferative effect of adiponectin also applies to the MDA-MB 231 estrogen
      insensitive breast epithelial cancer cell line. Our results demonstrate that i)
      the adiponectin-specific receptors AdipoR1 and R2 are expressed in these cells,
      and ii) the subphysiological concentrations of recombinant adiponectin inhibit
      MDA-MB 231 cell growth and concomitantly enhance the expression of Bax and p53,
      two pro-apoptotic genes. Moreover, the invalidation of AdipoR1 and R2 mRNA
      experiments demonstrated that the anti-proliferative and pro-apoptotic effects of
      adiponectin were partially mediated via AdipoR1 and R2. We describe, for the
      first time, that AdipoR mRNA expression was down-regulated by adiponectin and
      leptin in MDA-MB 231 cells. Taken altogether, these results strongly suggest that
      the two adipokines should be considered as i) additional factors of breast cancer
      risk, and ii) may therefore be potential targets in breast cancer therapy.

PMID- 18813843
TI  - Identification of tumor-associated antigens in human hepatocellular carcinoma by
      autoantibodies.
AB  - Hepatocellular carcinoma (HCC) is a major cause of death in Asian countries. The
      false-negative rate with serum alpha-fetaprotein level alone can reach 40% for
      early stage HCC patients. Due to the lack of sensitive and specific tumor markers
      for early diagnosis, it is impossible for HCC patients to receive effective
      therapy. However, tumor antigens can be recognized by immune cells and be
      rejected in immune responses. In order to identify antigens which may be used as
      new markers and immunotherapy targets for HCC, a cDNA expression library derived
      from an HCC sample was constructed, which was screened with mixed autologous and
      allogenic serum of HCC patients. Seventeen different HCC antigens were obtained,
      which are classified as tumor-associated antigens. A panel of allogenic sera from
      patients with chronic hepatitis, liver cirrhosis, HCC and other tumor entities
      and sera from health volunteers, was used for frequency analysis of antibody
      responses. Four of 17 antigens, including eukaryotic translation initiation
      factor 3, subunit I, lactate dehydrogenase 1, A chain, replication factor C2, 40
      kDa and mitochondrial carrier triple repeat 1, reacted predominantly with sera
      from patients with HCC (31.8, 45.5, 27.3 and 50.0% respectively). Patients
      (81.8%) with HCC had the antibody against at least one of these four antigens,
      which indicates that disease-specific humoral response against these antigens was
      induced in HCC patients and the corresponding antibodies may be used as tumor
      markers for HCC.

PMID- 18813844
TI  - Triple-negative breast cancer types exhibit a distinct poor clinical
      characteristic in lymph node-negative Chinese patients.
AB  - Comparative studies on the clinical features and outcomes of triple-negative
      subgroups to human epidermal growth factor receptor-2 (HER-2) overexpression, and
      luminal A and B subgroups in lymph node-negative breast cancer patients, are
      important to correctly evaluate clinical prognosis. A total of 1132 Chinese
      breast cancer patients were enrolled in a retrospective analysis. We
      characterized and identified prognostic information in the triple-negative
      subgroup [estrogen receptor (ER)-, progesterone receptor (PR)- and HER-2
      negative] and compared that to HER-2 overexpression, and the luminal A and B
      subgroups. By using immunohistochemical staining, the triple-negative subgroup
      showed 17% (193/1132) in the whole group. However, HER-2 overexpression, and the
      luminal A and B subgroups were 11.2, 47.9 and 23.9%, respectively. Tumors in the
      triple-negative subgroup showed a higher histological grade (P=0.025) and lower
      invasive ductal carcinoma (P=0.007), compared to the three subgroups. More
      patients in the luminal A subgroup had received adjuvant chemotherapy (P=0.007).
      The difference of disease-free survival rates among the four subgroups was
      significant (P=0.0001). The P-value for overall survival was 0.0598. No
      significant difference among the four subgroups in lymph node-positive and non
      chemotherapy breast cancers was found. From our data the poor clinical outcomes
      were independent of age, histological grade, tumor size, lymph nodal status,
      chemotherapy and clinical stages. Our data suggest that the triple-negative
      subgroup exhibits a distinct poor clinical outcome, especially in lymph node
      negative Chinese breast cancer patients.

PMID- 18813845
TI  - Molecular mapping of Factor XIIIa-enriched dendrocytes in the skin (Review).
AB  - The human dermis contains a series of dendritic cells which express different
      phenotypes including Factor XIIIa immunoreactivity. This compound is related to a
      blood coagulation factor participating in angiogenesis, in the final stages of
      the clotting cascade and in wound healing. In normal skin, Factor XIIIa is
      expressed in specific dermal dendrocytes (DD) derived from the
      monocyte/macrophage lineage or from a mesenchymal origin. DD are located
      predominantly around the microvasculature in the adventitial dermis, at the dermo
      epidermal junction, and around skin appendages, but normally not within the
      epidermis. Increased numbers of Factor XIIIa+ DD are present in a host of
      specific cutaneous inflammatory and fibrotic conditions. In tumor pathology,
      immunophenotypic differences are found between dermatofibromas and other
      fibrohistiocytic entities, most notably dermatofibrosarcoma protuberans. In
      addition, Factor XIIIa+ DD are likely to be involved in the progression and
      regression of some malignancies including cutaneous melanoma and basal cell
      carcinoma.

PMID- 18813846
TI  - Development of drug resistance in Trypanosoma brucei rhodesiense and Trypanosoma
      brucei gambiense. Treatment of human African trypanosomiasis with natural
      products (Review).
AB  - Human African trypanosomiasis is an infectious disease which has resulted in the
      deaths of thousands of people in Sub-Saharan Africa. Two subspecies of the
      protozoan parasite Trypanosoma brucei are the causative agents of the infection,
      whereby T. b. gambiense leads to chronic development of the disease and T. b.
      rhodesiense establishes an acute form, which is fatal within months or even
      weeks. Current chemotherapy treatment is complex, since special drugs have to be
      used for the different development stages of the disease, as well as for the
      parasite concerned. Melarsoprol is the only approved drug for effectively
      treating both subspecies of human African trypanosomiasis in its advanced stage,
      however, the drug's potency is constrained due to an unacceptable side effect:
      encephalopathy, which develops in one out of every 20 patients who are treated
      with the drug. In addition to the deleterious treatment with melarsoprol, the
      number of drug-resistant strains of T. brucei supp. increases. Mechanisms of drug
      resistance have been elucidated and involve decreased drug import through the
      loss of the purine transporter P2 as well as enhanced drug export, mediated by a
      multidrug resistance-associated protein called TbMRPA. Thereby, the medical
      treatment with the available chemotherapeutics becomes exceedingly difficult. A
      promising strategy for research into new drugs and moreover, to overcome drug
      resistance, are compounds derived from natural sources. This study provides an
      overview of the recently discovered small molecules with trypanocidal activity
      against T. b. gambiense and T. b. rhodesiense. In addition, former promising
      compounds are touched upon.

PMID- 18813848
TI  - Analyzing effects of extra-virgin olive oil polyphenols on breast cancer
      associated fatty acid synthase protein expression using reverse-phase protein
      microarrays.
AB  - Inhibitors of fatty acid synthase (FASN), a key enzyme involved in the anabolic
      conversion of dietary carbohydrates to fat in mammals, are receiving increasingly
      more attention as they may provide therapeutic moieties for the treatment of
      human malignancies. Natural compounds, such as the green tea polyphenol
      epigallocatechin-3-gallate, have been shown to induce anti-cancer effects by
      suppressing FASN, which may account for the epidemiologically observed inverse
      correlation between green-tea drinking and cancer risk in Oriental populations.
      Since extra-virgin olive oil (EVOO)-derived phenolics have been suggested to
      possess biological activities that may explain the health-promoting effects of
      the 'Mediterranean diet', we evaluated their effects on the expression of FASN
      protein in human breast epithelial cell lines. First, we developed a reverse
      phase protein microspot array (RPPA) capable of rapidly assessing the relative
      amount of FASN protein in whole lysates from cultured human cells. Then we tested
      the effects of phenolic fractions from EVOO and its main constituents including
      single phenols (i.e. tyrosol, hydroxytyrosol, vanillin), phenolic acids (i.e.
      caffeic acid, p-coumaric acid, vanillic acid, ferulic acid, elenolic acid),
      lignans (i.e. 1-[+]-pinoresinol, 1-[+]-acetoxy-pinoresinol), flavonoids (i.e.
      apigenin, luteolin), or secoiridoids (i.e. deacetoxyoleuropein aglycone,
      ligstroside aglycone, oleuropein glycoside, oleuropein aglycone) on FASN protein
      expression. EVOO polyphenols lignans, flavonoids and secoiridoids were found to
      drastically suppress FASN protein expression in HER2 gene-amplified SKBR3 breast
      cancer cells. Equivalent results were observed in MCF-7 cells engineered to
      overexpress the HER2 tyrosine kinase receptor, a well-characterized up-regulator
      of FASN expression in aggressive sub-types of cancer cells. EVOO-derived lignans,
      flavonoids and secoiridoids were significantly more effective than the mono-HER2
      inhibitor trastuzumab ( approximately 50% reduction) and as effective as the dual
      HER1/HER2 tyrosine kinase inhibitor lapatinib (> or =95% reduction) at
      suppressing high-levels of FASN protein in HER2-overexpressing SKBR3 and MCF
      7/HER2 cells. EVOO single phenols and phenolic acids failed to modulate FASN
      expression in SKBR3 and MCF-7/HER2 cells. These findings reveal for the first
      time that phenolic fractions, directly extracted from EVOO, may induce anti
      cancer effects by suppressing the expression of the lipogenic enzyme FASN in HER2
      overexpressing breast carcinoma cells, thus offering a previously unrecognized
      mechanism for EVOO-related cancer preventive effects.

PMID- 18813847
TI  - Expression of metalloprotease insulin-degrading enzyme insulysin in normal and
      malignant human tissues.
AB  - Insulin-degrading enzyme (IDE, insulysin, insulinase; EC 3.4.22.11), a thiol
      metalloendopeptidase, is involved in intracellular degradation of insulin,
      thereby inhibiting its translocation and accumulation to the nucleus. Recently,
      protein expression of IDE has been demonstrated in the epithelial ducts of normal
      breast and breast cancer tissue. Utilizing four different antibodies generated
      against different epitopes of the IDE molecule, we performed Western blot
      analysis and immunohistochemical staining on several normal human tissues, on a
      plethora of tumor cell lines of different tissue origin, and on malignant breast
      and ovarian tissue. Applying the four IDE-directed antibodies, we demonstrated
      IDE expression at the protein level, by means of immunoblotting and
      immunocytochemistry, in each of the tumor cell lines analyzed. Insulin-degrading
      enzyme protein expression was found in normal tissues of the kidney, liver, lung,
      brain, breast and skeletal muscle, as well as in breast and ovarian cancer
      tissues. Immunohistochemical visualization of IDE indicated cytoplasmic
      localization of IDE in each of the cell lines and tissues assessed. In
      conclusion, we performed for the first time a wide-ranging survey on IDE protein
      expression in normal and malignant tissues and cells thus extending our knowledge
      on the cellular and tissue distribution of IDE, an enzyme which to date has
      mainly been studied in connection with Alzheimer's disease and diabetes but not
      in cancer.

PMID- 18813849
TI  - Effect of vascular cell adhesion molecule 1 on fibroblasts in human eosinophilic
      chronic rhinosinusitis.
AB  - The pathogenesis of eosinophilic chronic rhinosinusitis (ECRS) is still unclear.
      Paranasal mucosa inflammation is thought to be related to eosinophilic
      infiltration. This infiltration seems to induce changes in the expression of cell
      adhesion molecules such as vascular cell adhesion molecule 1 (VCAM-1). The E
      cadherin-beta-catenin complex maintains the integrity of the epithelium.
      Downregulation of beta-catenin and E-cadherin is a pivotal factor for progressive
      cell growth. This study aimed to assess which cytokines regulate the expression
      of the adhesion molecule E-cadherin and the multi-functional protein beta
      catenin, which plays a key role in cadherin-mediated anchoring in ECRS. Cultured
      ECRS specimens were incubated with human VCAM-1. After a period of up to 72 h,
      expression of E-cadherin and beta-catenin was determined using cytokine
      immunoassay and immunohistochemistry. In ECRS, significant increases in E
      cadherin expression were found in fibroblast cell cultures. Stimulation with VCAM
      1 did not produce a significant alteration in the expression of the adherens
      junction protein beta-catenin. In addition, VCAM-1 did not decrease the levels of
      membrane staining for adherens junction proteins. The selective increase in E
      cadherin expression in eosinophilic fibroblast cultures might be explained by a
      higher concentration of the Th2-type cytokines in these cultures. The tissue
      remodelling observed during chronic eosinophilic inflammation offers new insight
      into the pathogenesis of ECRS.

PMID- 18813850
TI  - Derivation of hepato-pancreatic intermediate progenitor cells from a clonal
      mesenchymal stem cell line of rat bone marrow origin.
AB  - We have recently established a clonal mesenchymal stem cell line (rBM25/S3) from
      adult rat bone marrow. The cells have practically unlimited proliferation
      capacity (over 300 PDL), maintaining multipotency for differentiation. In the
      present study, we examined the potential for rBM25/S3 cells to differentiate into
      insulin-secreting cells. When cultured in the presence of HGF and FGF-4 on
      Matrigel, rBM25/S3 cells expressed genes specific to pancreatic beta-cells as
      well as those specific to hepatocytes. They still maintained proliferation
      capacity with a doubling time of approximately 30 h. These hepato-pancreatic
      intermediate progenitor cells, but not the original undifferentiated rBM25/S3
      cells, were induced by the overexpression of PDX-1 to produce significant amounts
      of insulin in a manner responding to glucose concentration in medium. The present
      culture system indicates a direction for further studies aimed at the realization
      of cell transplantation therapy for type I diabetes mellitus.

PMID- 18813851
TI  - Bcr/Abl P190 interaction with Spa-1, a GTPase activating protein for the small
      GTPase Rap1.
AB  - The Bcr/Abl oncogene is responsible for the development of Ph-chromosome positive
      acute lymphoblastic leukemia and chronic myelogenous leukemia in humans. Previous
      studies demonstrated that Bcr/Abl expression is associated with elevated levels
      of activated Rap1, a small GTPase. Levels of activated Rap1 are determined by a
      balance between GTPase activating and G-nucleotide exchange factor activity. We
      show that Bcr/Abl forms a protein-protein complex with Spa-1, a GTPase activating
      protein for Rap1, both in COS-1 cells as well as in primary lymphoblastic
      leukemia cells from a transgenic P190 BCR/ABL mouse model. The interaction
      between Spa-1 and P190 did not affect the tyrosine kinase activity of P190, nor
      did Spa-1 become phosphorylated on tyrosine as a result of the interaction. P190
      and Spa-1 co-localized to peripheral actin structures in primary lymphoblasts and
      expression of Spa-1 in the leukemic lymphoblasts decreased the migration of these
      cells. The binding of Bcr/Abl to Spa-1 may cause aberrant subcellular location of
      Spa-1 and affect migration of these cells.

PMID- 18813852
TI  - Urokinase-type plasminogen activator receptor is associated with macrophages and
      plaque rupture in symptomatic carotid atherosclerosis.
AB  - There is a strong correlation between macrophage infiltration and plaque
      instability in recently symptomatic carotid atherosclerotic plaques, and it is
      hypothesised that mechanisms related to macrophages may be involved in plaque
      vulnerability and rupture. We previously found high expression of urokinase-type
      plasminogen activator receptor (UPAR) in human macrophages. The aim of this study
      was to investigate whether UPAR co-localises with macrophages in symptomatic
      carotid plaques, and whether UPAR expression is associated with plaque rupture.
      Real-time RT-PCR assays showed that UPAR expression levels were high in monocyte
      derived macrophages and in carotid endarterectomies compared with a tissue panel.
      Serial transverse sections were prepared from carotid endarterectomies from 12
      symptomatic patients, and analyzed with immunohistochemical staining for UPAR and
      for CD68-positive macrophages, and with histopathological assessment. UPAR co
      localised with CD68-positive macrophages, with a high correlation (r=0.90,
      p<0.001) between immunostained areas in 12 carotid endarterectomies from
      symptomatic patients. High degrees of UPAR and CD68 staining were found in
      sections around the bifurcation level where rupture was most common, while low
      degrees of staining were found in sections of the common carotid artery end of
      the endarterectomy (p<0.05). Higher degrees of UPAR staining were observed in
      ruptured plaque sections compared with non-ruptured sections. In conclusion, UPAR
      was highly expressed in monocyte-derived macrophages and in symptomatic carotid
      plaques, UPAR co-localised with macrophages in carotid symptomatic plaques and
      UPAR was predominantly found in ruptured plaque segments. These findings support
      the hypothesis that UPAR is related to plaque rupture in symptomatic
      atherosclerotic lesions.

PMID- 18813853
TI  - Characterization of colon carcinoma growth pattern by computerized morphometry:
      definition of a complexity index.
AB  - The invasive front of carcinomas may vary in complexity from smooth to highly
      complex when the front splits up into small cell clusters or even single cancer
      cells. The degree of complexity is usually estimated visually and
      semiquantitatively by a pathologist, although more objective methods based on
      computer-assisted image analysis are available. In this study, we compared the
      visual estimation of the irregularity of the tumour invasion front of colon
      carcinomas to different quantitative image analytical techniques and defined a
      complexity index for the invasive margin. Sections from 29 archived colon
      carcinomas were stained immunohistochemically for cytokeratin 8. Images of the
      tumour invasion front were read into a computer and thresholded so that the
      tumour tissue became black and the background white or so that the tumour front
      was outlined by a single pixel line. The invasive front was visually classified
      into four degrees of irregularity by a pathologist. The complexity of the front
      was then assessed using four different image analysis techniques, i.e. the
      estimation of fractal dimension, tumour front length, number of tumour cell
      clusters and lacunarity. Fractal dimension and tumour cell clusters together gave
      the best correlation to visual grading using a discriminant analysis. A cluster
      analysis and a tree diagram analysis were then performed and were found to be
      superior to visual estimation. The clusters represent different degrees of
      complexity and the result of the tree diagram analysis can be used to assign
      complexity indices to colon tumours. The fractal dimension separated tumours up
      to a certain level (1.5-1.6) of complexity. When the tumour front split up into
      small cell clusters, the counting of tumour cell clusters separated the cells
      over and above the fractal dimension. This new technique can be used to
      objectively and quantitatively describe the complexity of the invasive front of
      tumours.

PMID- 18813854
TI  - Abrogation of TGF-beta by antisense oligonucleotides modulates expression of VEGF
      and increases angiogenic potential in isolated fibroblasts from radiated skin.
AB  - The transforming growth factor-beta (TGF-beta) has been identified as an
      important component of wound healing. Recent developments in molecular therapy
      offer good prospects for the modulation of wound healing, specifically those
      targeting TGF-beta. The aim of this study was to analyze the effect of TGF-beta
      targeting on the expression of angiogenic vascular endothelial growth factor
      (VEGF), a key regulator of angiogenesis and in vitro angiogenic activity in
      fibroblasts isolated from radiation-induced chronic dermal wounds. The expression
      of angiogenic VEGF in tissue samples from radiation-induced chronic dermal wounds
      was investigated by immunohistochemistry and microarray technique. The effect of
      TGF-beta targeting using antisense oligonucleotides on the expression of VEGF in
      isolated fibroblasts was analyzed by ELISA and multiplex RT-PCR. Human
      endothelial cells (ECs) were grown in conditioned medium produced from the
      treated fibroblasts. EC migration was measured using a modified Boyden chamber;
      EC tube formation was analyzed under a light microscope. Immunohistochemical
      investigation and microarray analysis demonstrated a decreased expression of VEGF
      protein and mRNA in tissue samples from radiation-induced chronic dermal wounds
      compared to normal human skin. Antisense TGF-beta oligonucleotide treatment
      significantly up-regulated VEGF secretion in vitro. Addition of conditioned
      medium from TGF-beta antisense-treated fibroblasts resulted in an increase in EC
      cell migration and tube formation. In conclusion, our results demonstrate that
      TGF-beta antisense oligonucleotide technology may be a potential therapeutic
      option for stimulation of angiogenesis in radiation-induced dermal wounds.

PMID- 18813855
TI  - Beneficial effect of Flos magnoliae extract on multiple low dose streptozotocin
      induced type 1 diabetes development and cytokine-induced beta-cell damage.
AB  - In the present study, Flos magnoliae extract (FME) was evaluated to determine if
      it could protect pancreatic beta-cells against multiple low dose streptozotocin
      (MLDS) and interleukin-1beta and interferon-gamma. Injection of mice with MLDS
      resulted in hyperglycemia and hypoinsulinemia, which was confirmed by
      immunohistochemical staining. However, the induction of diabetes by MLDS was
      completely prevented when mice were pretreated with FME. FME also effectively
      protected beta-cells against cytokine toxicity, which was demonstrated by an
      increase in the viability of rat insulinoma RINm5F cells and by preserved insulin
      secreting responses to glucose in isolated rat islets. Moreover, cytokine-induced
      nitric oxide production and iNOS mRNA and protein expression were significantly
      reduced in RINm5F cells and islets that were preincubated with FME. The molecular
      mechanism by which FME inhibits iNOS gene expression in in vitro and in vivo
      appears to involve inhibition of NF-kappaB activation. Taken together, these
      results reveal the possible therapeutic value of FME for the prevention of type 1
      diabetes progression.

PMID- 18813856
TI  - Triptolide overcomes dexamethasone resistance and enhanced PS-341-induced
      apoptosis via PI3k/Akt/NF-kappaB pathways in human multiple myeloma cells.
AB  - Human multiple myeloma is a presently incurable hematological malignancy and
      novel biologically based therapies are urgently needed. Triptolide (TPL) is a
      purified diterpenod isolated from the Chinese herb, Tripterygium wilfordii Hook.
      F that has shown antitumor activities in various cancer cell types. But its
      activity in Dex-resistant multiple myeloma cell lines and the main upstream
      signaling pathway has not been reported. Here we show that TPL induces apoptosis
      in dexamethasone-sensitive (MM.1S) and dexamethasone-resistant (MM.1R) cells,
      most importantly its main upstream signaling pathway is through the PI3k/Akt/NF
      kappaB pathway and is also associated with MAPK pathway, via mitochondrial
      apoptotic signaling and is also associated with the caspase and Bcl-2 family
      members. Moreover, TPL was able to enhance the activities of dexamethasone or
      bortezomib/PS-341 in multiple myeloma cell lines. Collectively, these findings
      provide the framework for a clinical evaluation of TPL, either alone or in
      combination with dexamethasone or bortezomib/PS-341, to overcome drug resistance
      and improve outcome for patients with this universally fatal hematological
      malignancy.

PMID- 18813857
TI  - Evaluation of apoptotic cells and immunohistochemical detection of FAS, FAS-L,
      Bcl-2, Bax, p53 and c-Myc in the skin of patients with chronic venous leg ulcers.
AB  - In the present study we were interested, if apoptosis plays a role in the
      surrounding skin of venous ulcers, where microcirculatory disorders were already
      observed. For this purpose laser Doppler flow and partial oxygen pressure were
      measured in 17 patients at the ulcer edge, the transitional area of the lower leg
      and the thigh. Subsequently biopsies were taken from the respective sites and
      subjected to terminal deoxynucleotidyl transferase labelling (TUNEL) and
      immunohistochemistry using antibodies to determine the protein expression of Fas,
      Fas-L, Bax, Bcl-2, p53 and c-Myc. Laser Doppler flow was increased and
      transcutaneous oxygen partial pressure was decreased, with significant
      differences at the ulcer edge and the lower leg compared to the thigh. The skin
      biopsies did not show any differences when labelling for apoptotic cells.
      Keratinocytes of basal and spinous layer stained with antibodies against Fas, Fas
      L and Bax in all probes of the three sites. c-Myc and p53 were negative in all
      keratinocytes of the skin probes. However, staining with Bcl-2 was significantly
      decreased at the ulcer edge in comparison to the lower leg and the thigh
      (p=0.017). Our study revealed that a disturbed microcirculation does not increase
      the number of apoptotic cells at the ulcer edge in patients with venous disease.
      The reduced staining pattern with Bcl-2 at the ulcer edge seems not to result in
      higher susceptibility to apoptosis, but it remains to be proven whether it is
      involved in epidermal acanthosis.

PMID- 18813858
TI  - Novel mutations in the IRF6 gene in Brazilian families with Van der Woude
      syndrome.
AB  - Van der Woude Syndrome (VWS) is an autosomal craniofacial disorder characterized
      by lower lip pits and cleft lip and/or palate. Mutations in the interferon
      regulatory factor 6 (IRF6) gene have been identified in patients with VWS. To
      identify novel IRF6 mutations in patients affected by VWS, we screened 2
      Brazilian families, sequencing the entire IRF6-coding region and flanking
      intronic boundaries. Two novel heterozygous mutations were identified: a frame
      shift mutation with deletion of G at the nucleotide position 520 in the exon 6
      (520delG), and a missense single nucleotide substitution from T to A at
      nucleotide position 1135 in exon 8 (T1135A). By using restriction enzyme
      analysis, we were able to demonstrate the lack of similar mutations in unrelated
      healthy individuals and non-syndromic cleft lip and palate patients. Our results
      further confirmed that haploinsufficiency of the IRF6 gene results in VWS.

PMID- 18813859
TI  - Visible and near-infrared spectral changes in plasma of psychiatric patients.
AB  - In the present study, the possible difference in visible and near-infrared (Vis
      NIR) spectra of plasma in psychiatric patients compared to healthy control
      subjects was investigated. Mean Vis-NIR spectra of 60 psychiatric patients showed
      several specific peaks in the 630- to 930-nm region. Principal component analysis
      (PCA) and soft independent modeling of class analogy (SIMCA) were applied to
      manifest the spectral characteristics of each group. The PCA and SIMCA models
      demonstrated successful discrimination of the two groups using a score plot of
      the third versus fourth principal component and a Coomans plot, respectively. The
      PCA loadings were generally consistent with the discriminating power of the SIMCA
      model, indicating a specific pattern of Vis-NIR spectra in the plasma of
      psychiatric patients. The specific pattern possibly indicates altered superoxide,
      amine, and primary and secondary amides in plasma and may provide a possible
      indicator for the diagnosis of heterogeneous psychiatric disorders. This is the
      first step toward a clinical tool which has the potential to be applied in the
      diagnosis of psychiatric disease. Yet, there remain obstacles to its practical
      usage.

PMID- 18813860
TI  - Therapeutic effect of ARBs on insulin resistance and liver injury in patients
      with NAFLD and chronic hepatitis C: a pilot study.
AB  - Fatty liver is one of the local morphological manifestations of metabolic
      syndrome and is frequently associated with insulin resistance. Insulin resistance
      is also common in patients with chronic hepatitis C. Hyperinsulinemia is an
      independent risk factor for hypertension and cardiovascular mortality. The aim of
      this study was to evaluate the therapeutic efficacy of angiotensin II receptor
      blockers (ARBs), telmisartan and olmesartan, for patients with non-alcoholic
      fatty liver disease (NAFLD) and chronic hepatitis C (CH-C). We analyzed the
      incidence of obesity, insulin resistance, and other disorders in patients with
      NAFLD (Group A), CH-C (Group B), or other liver diseases (Group C). We evaluated
      whether the ARBs, telmisartan and olmesartan, improved insulin resistance and
      liver injury by measuring the homeostasis model assessment ratio of insulin
      resistance (HOMA-IR) and serum alanine aminotransferase (ALT). The incidence of
      obesity (BMI > or =25 kg/m2) was significantly higher in Group A than in Groups B
      and C. The incidence of insulin resistance (HOMA-IR > or =2.5) in Groups A and B
      was significantly higher than in Group C. Regular doses of telmisartan and
      olmesartan significantly improved HOMA-IR and ALT levels not only in NAFLD
      patients but also in patients with CH-C. The effects tended to be more notable
      with telmisartan. In conclusion, telmisartan and olmesartan improved insulin
      sensitivity and may possibly be used as liver protecting agents in CH-C as well
      as NAFLD patients.

PMID- 18813861
TI  - Exercise training acts as a therapeutic strategy for reduction of the pathogenic
      phenotypes for Alzheimer's disease in an NSE/APPsw-transgenic model.
AB  - Alzheimer's disease (AD) is a progressive neurodegenerative disease for which
      there are few therapeutic regimens that influence the underlying pathogenic
      phenotypes. However, of the currently available therapies, exercise training is
      considered to be one of the best candidates for amelioration of the pathological
      phenotypes of AD. Therefore, we directly investigated exercise training to
      determine whether it was able to ameliorate the molecular pathogenic phenotypes
      in the brain using a neuron-specific enolase (NSE)/Swedish mutation of amyloid
      precursor protein (APPsw) transgenic (Tg) mice as a novel AD model. To accomplish
      this, Non-Tg and NSE/ APPsw Tg mice were subjected to exercise on a treadmill for
      16 weeks, after which their brains were evaluated to determine whether any
      changes in the pathological phenotype-related factors had occurred. The results
      indicated (i) that amyloid beta-42 (Abeta-42) peptides were significantly
      decreased in the NSE/APPsw Tg mice following exercise training; (ii) that
      exercise training inhibited the apoptotic biochemical cascades, including
      cytochrome c, caspase-9, caspase-3 and Bax; (iii) that the glucose transporter-1
      (GLUT-1) and brain-derived neurotrophic factor (BDNF) proteins induced by
      exercise training protected the neurons from injury by inducing the concomitant
      expression of genes that encode proteins such as superoxide dismutase-1 (SOD-1),
      catalase and Bcl-2, which suppress oxidative stress and excitotoxic injury; (iv)
      that heat-shock protein-70 (HSP-70) and glucose-regulated protein-78 (GRP-78)
      were significantly increased in the exercise (EXE) group when compared to the
      sedentary (SED) group, and that these proteins may benefit the brain by making it
      more resistant to stress-induced neuron cell damage; (v) and that exercise
      training contributed to the restoration of normal levels of serum total
      cholesterol, insulin and glucose. Taken together, these results suggest that
      exercise training represents a practical therapeutic strategy for human subjects
      suffering from AD. Moreover, this training has the potential for use in new
      therapeutic strategies for the treatment of other chronic disease including
      diabetes, cardiovascular and Parkinson's disease.

PMID- 18813862
TI  - Antiviral effects of ascorbic and dehydroascorbic acids in vitro.
AB  - In the present study, ascorbic acid weakly inhibited the multiplication of
      viruses of three different families: herpes simplex virus type 1 (HSV-1),
      influenza virus type A and poliovirus type 1. Dehydroascorbic acid, an oxidized
      form of ascorbic acid and hence without reducing ability, showed much stronger
      antiviral activity than ascorbic acid, indicating that the antiviral activity of
      ascorbic acid is due to factors other than an antioxidant mechanism. Moreover,
      addition of 1 mM Fe3+, which oxidizes ascorbic acid to dehydroascorbic acid and
      also enhances the formation of hydroxyl radicals by ascorbic acid in the culture
      media, strongly enhanced the antiviral activity of ascorbic acid to a level
      significantly stronger than that of dehydroascorbic acid. Although both ascorbic
      acid and dehydroascorbic acid showed some cytotoxicity, the degree of
      cytotoxicity of the former was 10-fold higher than the latter, suggesting that
      the observed antiviral activity of ascorbic acid with and without ferric ion is,
      at least in part, a secondary result of the cytotoxic effect of the reagent, most
      likely due to the free radicals. However, the possibility that oxidation of
      ascorbic acid also contributed to the antiviral effects of ascorbic acid exists,
      in particular in the presence of ferric ion, since dehydroascorbic acid exhibited
      a very strong antiviral activity. Characterization of the mode of antiviral
      action of dehydroascorbic acid revealed that the addition of the reagent even at
      11 h post infection almost completely inhibited the formation of progeny
      infectious virus in the infected cells, indicating that the reagent inhibits HSV
      1 multiplication probably at the assembly process of progeny virus particles
      after the completion of viral DNA replication.

PMID- 18813863
TI  - Evaluation of novel cyclic analogues of apelin.
AB  - Apelin regulates various cell signaling processes through interaction with its
      specific cell-surface receptor, APJ, which is a member of a seven transmembrane G
      protein-coupled receptor superfamily. To develop a novel apelin analogue, we
      synthesized cyclic analogues of minimal apelin fragment RPRLSHKGPMPF (apelin-12),
      and evaluated their bioactivities in a recombinant human APJ-expressed cell line.
      Three cyclic analogues were synthesized: cyclo apelin-12 (C1) in combination with
      amino-terminal to carboxy-terminal, cyclourea apelin-12 (C3) in combination with
      amino-terminal and amino acid side chain at positions 7, and cyclic apelin-12
      (C4) in combination with amino acid side chain at positions 7 to carboxy
      terminal. All cyclic analogues exhibited dose-dependent inhibitory effects
      against forskolin-induced cyclic adenosine monophosphate (cAMP) accumulation, and
      the maximal effects were almost abolished by pertussis toxin (PTx) treatment.
      Moreover, they could modulate the intracellular signaling pathways composed of
      Akt and extracellular signal-regulated kinase 1/2 (ERK1/2) serine/threonine
      protein kinases in PTx-sensitive manner. This is the first approach to apply
      cyclization on apelin, and these results provide the basis for the development of
      drug-like apelin analogues.

PMID- 18813864
TI  - Expression of precerebellins in cultured rat calvaria osteoblast-like cells.
AB  - Cerebellin (CER), originally isolated from rat cerebellum, is a hexadecapeptide
      derived from the larger precursor called precerebellin 1 (Cbln1). At present 4
      propeptides designated as Cbln1, Cbln2, Cbln3 and Cbln4 are recognized. They
      belong to precerebellin subfamily of the C1q family proteins. Precerebellins act
      as transneuronal regulators of synapse development and synaptic plasticity in
      various brain regions. Initially CER was thought to be a cerebellum specific
      peptide, however subsequent studies revealed its presence in other brain regions
      as well as in extraneuronal tissues. We investigated whether precerebellins are
      expressed and involved in regulation of cultured rat calvarial osteoblast-like
      (ROB) cells. Classic RT-PCR revealed the presence of Cbln1 and Cbln3 mRNA in
      fragments of rat calvaria, in freshly isolated ROB cells and in ROB cells
      cultured for 7, 14 and 21 days. Cbln2 and Cbln4 mRNA, on the other hand, could
      not be demonstrated in ROB cells but was found to be present in the brain. In
      freshly isolated ROB cells expression of Cbln1 gene was very low and gradually
      increased in relation to the duration of culture. Expression of Cbln3, on the
      other hand, was very low in fragments of rat calvaria, and increased notably
      after digestion with collagenase-I. The highest expression of this precerebellin
      was observed at day 14 of culture while at days 7 and 21 levels of expressions
      were notably lower. Neither Cbln2 nor Cbln4 was found to be expressed in the ROB
      cells. Neither CER nor des-Ser1-CER (10(-10)-10(-6)M) affect osteocalcin
      production and proliferation rate of studied cells. The above findings suggest
      that CER, which theoretically would be derived from Cbln1, modulate neither
      differentiated (osteocalcin secretion) nor basic (proliferation) functions of
      cultured rat osteoblast-like cells. The obtained data raise an intriguing
      hypothesis that precerebellins may be involved in regulating of spatial
      organization of osteoblastic niches in the bone.

PMID- 18813865
TI  - Fatty acid profile of plasma and liver lipids in mice depleted in long-chain
      polyunsaturated (n-3) fatty acids.
AB  - Considering the numerous features of the metabolic syndrome found in rats
      depleted in long-chain polyunsaturated (n-3) fatty acids and in the perspective
      of further work conducted in (n-3)-depleted mice, the fatty acid profile of
      plasma and liver lipids was assessed in both male and female control and second
      generation (n-3)-depleted mice. In addition to gender differences, the major
      alteration found in the (n-3)-depleted animals consisted in the expected severe
      depletion of plasma triacylglycerols and phospholipids, as well as liver
      phospholipids, in C20:5(n-3), C22:5(n-3) and C22:6(n-3). In plasma
      triacylglycerols, the weight percentages of C18:2(n-6) and C18:3(n-6) were lower
      in (n-3)-depleted mice than in control animals. In both plasma and liver
      phospholipids, however, the weight percentages of long-chain polyunsaturated (n
      6) fatty acids (C20:4(n-6) and C22:4(n-6)) were higher in (n-3)-depleted mice
      than in control animals. The C16:1(n-7)/C16:0 and C18:1(n-9)/C18:0 ratio in both
      plasma and liver phospholipids were also increased in female (n-3)-depleted mice
      but not so in male animals. Highly significant correlations were found between
      the weight percentage of each fatty acid in liver versus plasma phospholipids.
      Taken as a whole, these findings indicate that second-generation mice depleted in
      (n-3) fatty acids represent a suitable model, in terms of the remodelling of the
      fatty acid profile in plasma and liver lipids, to investigate the metabolic and
      functional consequences of such a depletion.

PMID- 18813866
TI  - Hypolipidemic effect of Shoyu polysaccharides from soy sauce in animals and
      humans.
AB  - Soy sauce (Shoyu) is a traditional Japanese fermented seasoning and is available
      worldwide. We investigated the effects of Shoyu polysaccharides (SPS) prepared
      from soy sauce on hyperlipidemia in vitro and in vivo. First, SPS inhibited
      pancreatic lipase. Second, in experiments with animals, it was found that SPS
      reduced serum triacylglycerol (TG) elevation induced by high-fat diets. Third, in
      a 2-week placebo-controlled parallel group study, healthy men (TG <150 mg/dl)
      were treated with 600 mg of SPS (n=5) or placebo (n=5) every day. After 2 weeks,
      serum TG elevation was significantly (P<0.05) lower in the SPS-treated group than
      in the placebo-treated group after 6 h of a high-fat diet. Fourth, in a 4-week
      randomized, double-blind, placebo-controlled parallel group study, hyperlipidemic
      men (TG >150 mg/dl) were treated with 600 mg of SPS (n=15) or placebo (n=15)
      daily. After 4 weeks, serum TG levels in the SPS-treated group were significantly
      (P<0.05) lower than the baseline (0 week). In conclusion, SPS of soy sauce reduce
      lipid absorption, and soy sauce is a potentially promising seasoning for the
      treatment of hyperlipidemia through food.

PMID- 18813869
TI  - Contribution to the 3D computer assisted reconstruction of pancreatic buds in the
      rat embryos.
AB  - The aim of this work was to reconstruct, in the rat embryos, stage 12-23, the
      three dimensional (3D) distribution of the dorsal and ventral pancreatic buds by
      of a computer assisted method. Ninety-six rat embryos, CRL 3-16 mm, fixed,
      dehydrated, and paraffin embedded, were submitted to serial histological sections
      and stained by hematoxylin-eosin and Heidenhain's azan techniques. The images
      were digitalized by Canon Camera 350 EOS D. The serial views were aligned
      anatomically by software and the data were analyzed following segmentation and
      thresholding. The dorsal pancreas developed from the dorsal wall of the duodenum
      in stage 12, while the ventral pancreas arose from the ventral wall of the
      hepatic diverticulum in stage 13 and 14. The rotation of ventral pancreas started
      in stage 15 and was completed in stage 16. The fusion of both buds was evident in
      stage 17. In stage 23 the limit between dorsal and ventral bud was still marked
      by the pathway of superior mesenteric vein.

PMID- 18813868
TI  - Acid-suppressive medications and risk of bone loss and fracture in older adults.
AB  - Recent studies have suggested an increased fracture risk with acid-suppressive
      medication use. We studied two cohorts of men and women over age 65 who were
      enrolled in the Osteoporotic Fractures in Men Study (MrOS) and the Study of
      Osteoporotic Fractures (SOF), respectively. We used dual-energy X-ray
      absorptiometry and assessed baseline use of proton pump inhibitors (PPIs) and/or
      H2 receptor antagonists (H2RAs) in 5,755 men and 5,339 women. Medication use and
      bone mineral density (BMD) were assessed, and hip and other nonspine fractures
      were documented. On multivariate analysis, men using either PPIs or H2RAs had
      lower cross-sectional bone mass. No significant BMD differences were observed
      among women. However, there was an increased risk of nonspine fracture among
      women using PPIs (relative hazard [RH] = 1.34, 95% confidence interval [CI] 1.10
      1.64). PPI use was also associated with an increased risk of nonspine fracture in
      men but only among those who were not taking calcium supplements (RH = 1.49, 95%
      CI 1.04-2.14). H2RA use was not associated with nonspine fractures, and neither
      H2RA use nor PPI use was associated with incident hip fractures in men or women.
      The use of PPIs in older women, and perhaps older men with low calcium intake,
      may be associated with a modestly increased risk of nonspine fracture.

PMID- 18813870
TI  - Mutation spectra of the surface-protein-coding region of the HBV genome in HBV
      vaccinated and non-vaccinated individuals in Hungary.
AB  - Hepatitis B virus (HBV) infection has a major effect on health care systems, with
      about one-third of the world's population currently infected with the virus.
      There is an effective vaccine against HBV, which contains a recombinant "surface
      antigen" produced in an expression vector. Vaccination has proved to be
      successful in Hungary: the number of acute HBV cases has decreased in the past 10
      years. Although an increasing number of publications report on "vaccine-escape"
      HBV variants which can infect HBV-vaccinated individuals, such mutant HBV strains
      have not yet been detected in Hungary. We therefore surveyed two risk groups for
      vaccine-escape or immunoglobulin-escape HBV mutations in Hungary: 28 actively
      and/or passively HBV-immunized children of HBV carrier mothers who proved to be
      HBsAg and/or anti-HBc positive and 40 symptomless HBV carrier pregnant women
      (presumably carrying genotype B or C). We focused on the coding sequences of the
      "a" immundominant region of the surface protein. We could not detect the G145R
      amino acid substitution associated with vaccine escape mutant virus. However, we
      could map other mutations potentially affecting the immunodominant "a" region of
      the HBV surface protein.

PMID- 18813871
TI  - Lactic acid bacteria prevent alcohol-induced steatohepatitis in rats by acting on
      the pathways of alcohol metabolism.
AB  - The objective is to study the possible mechanism by which lactic acid bacteria
      (LAB) prevent alcohol-induced steatohepatitis in rats. A total of 25 Wistar rats
      were divided into three groups: a LAB-fed group, an alcohol-treated group and a
      control group. Both the LAB-fed group and the alcohol-treated group received
      alcohol (10 g kg(-1) per day) orally for up to 5 days (125 h). Before exposure to
      alcohol, the LAB-fed group were first treated daily with 1.5 ml/100 g of a
      mixture comprising 4 x 10(10) ml(-1) of Lactobacillus acidophilus and 2.5 x 10(7)
      ml(-1) of Bifidobacterium longum, while the control group was treated with normal
      saline only. Biochemical data, alcohol dehydrogenase (ADH) activity and histology
      of the liver and stomach were evaluated. The ADH activity in the LAB mixture was
      3.52 +/- 0.45 mumol mg(-1) protein (10(9) CFU ml(-1)), and was dose-dependent. By
      30 min after taking alcohol, serum alcohol concentrations were 514.24 +/- 80.21
      microg ml(-1) in the LAB-fed group and 795.15 +/- 203.45 microg ml(-1) in the
      alcohol-treated group (P < 0.005). Serum alcohol concentrations were reduced by
      48% (P < 0.01) in the LAB-fed group, but by only 4% in the alcohol-treated group
      (P > 0.05) 120 min after oral intake of alcohol. The blood levels of endotoxin,
      AST and ALT were improved in the LAB-fed group compared to the alcohol-fed group
      (P < 0.01). All alcohol-treated rats showed moderate to severe steatohepatitis,
      but the LAB-fed rats showed almost normal histology or very slight lesions only.
      In conclusion, LAB decreased the alcohol concentration in the blood by increasing
      the first-pass metabolism in both the stomach and the liver, and effectively
      protected against alcohol-induced gastric and liver injury. It is interesting to
      note that the protection was more effective in the liver.

PMID- 18813873
TI  - Risk of second tumor in intracranial germinoma patients treated with radiation
      therapy: the Johns Hopkins experience.
AB  - BACKGROUND: We reviewed the risk of second tumor (ST), both malignant and benign,
      in germinoma survivors followed at the Johns Hopkins Hospital (JHH). METHODS:
      Between 1977 and 2002, 27 patients with intracranial germinoma were treated with
      radiation therapy (RT). In the presence of competing events, a cumulative
      incidence function of ST was estimated using the minimal time interval from the
      date of diagnosis to the date of ST, date of death, or date of last follow-up.
      RESULTS: Five patients (18%) developed a ST of which 4 (15%) were malignant. One
      developed a benign falcine meningioma. The cumulative incidence of ST was 9% at
      11 years (95% CI, 0-22%). CONCLUSIONS: The relative contributions of RT and
      patient susceptibility to a ST cannot be determined but suggests the need for
      long-term surveillance, including testicular self-exams in male germinoma
      survivors. Current trials of chemotherapy and reduced RT dose and volume offer
      the prospect of a lower risk of treatment-induced ST.

PMID- 18813874
TI  - Comparative analysis of temozolomide (TMZ) versus 1,3-bis (2-chloroethyl)-1
      nitrosourea (BCNU) in newly diagnosed glioblastoma multiforme (GBM) patients.
AB  - PURPOSE: Although TMZ replaced BCNU as the standard initial chemotherapy in the
      treatment of GBM, no studies have been reported comparing BCNU with TMZ. We
      therefore did a retrospective analysis comparing these agents as initial therapy
      in GBM. PATIENTS AND METHODS: Eighty-one patients with GBM in our institution
      received both radiation and chemotherapy as initial treatment after surgery or
      biopsy; 49 receiving BCNU and 32 TMZ. These were analyzed for overall survival
      (OS) and progression-free survival (PFS) versus the type of chemotherapy used.
      The influence of salvage therapy on the outcome was investigated also. RESULTS:
      Median OS was superior in the TMZ versus the BCNU group (15.9 vs. 11.5 months)
      and the curves were judged to be significantly different by the log-rank test; P
      < 0.02. However, PFS was not significantly different between the two groups.
      Bevacizumab plus irinotecan (BI) was used as salvage therapy in one-third of the
      TMZ patients but in none of the BCNU patients. When patients receiving BI were
      omitted from the TMZ group the OS curve overlapped that of BCNU patients.
      CONCLUSION: These data suggest that the superior OS of the TMZ-treated GBM
      patients was not due to better tumor control by TMZ but was possibly related to
      the newer salvage therapy that was available to them.

PMID- 18813875
TI  - Survival benefit of Boron neutron capture therapy for recurrent malignant
      gliomas.
AB  - We have applied boron neutron capture therapy (BNCT) to malignant brain tumors.
      Here we evaluated the survival benefit of BNCT for recurrent malignant glioma
      (MG). Since 2002, we have treated 22 cases of recurrent MG with BNCT. Survival
      time was analyzed with special reference to recursive partitioning analysis (RPA)
      classification, by Carson et al. (J Clin Oncol 25:2601-2606, 2007). Median
      survival times (MSTs) after BNCT for all patients and for glioblastoma as on
      study histology at recurrence was 10.8 months (n = 22; 95% CI, 7.3-12.8 months)
      and 9.6 months (n = 19; 95% CI, 6.9-11.4 months), respectively. In our study, MST
      for the high-risk RPA classes was 9.1 months (n = 11; 95% CI, 4.4-11.0 months).
      By contrast, the original journal data showed that the MST of the same RPA
      classes was 4.4 months (n = 129; 95% CI, 3.6-5.4 months). BNCT showed a survival
      benefit for recurrent MG, especially in the high-risk group.

PMID- 18813877
TI  - Species as a process.
AB  - Species are generally considered to be the basic units of evolution, and hence to
      constitute spatio-temporally bounded entities. In addition, it has been argued
      that species also instantiate a natural kind. Evolution is fundamentally about
      change. The question then is how species can remain the same through evolutionary
      change. Proponents of the species qua individuals thesis individuate species
      through their unique evolutionary origin. Individuals, or spatio-temporally
      located particulars in general, can be bodies, objects, events, or processes, or
      a combination of these. It is here argued that species are best understood as
      open or closed, causally integrated processual systems that also instantiate an
      historically conditioned homeostatic property cluster natural kind.

PMID- 18813876
TI  - What is the translational efficacy of chemotherapeutic drug research in neuro
      oncology? A systematic review and meta-analysis of the efficacy of BCNU and CCNU
      in animal models of glioma.
AB  - INTRODUCTION: The translational value of experimental therapeutic neuroscience
      research to clinical practice is highly variable. This has been particularly well
      demonstrated in the field of neuroprotective agents following either head injury
      or stroke. In this study we evaluate the efficacy of systemic BCNU and CCNU in
      experimental glioma models and how the experimental data has translated into
      clinical practice. METHODS: A systematic review of the efficacy of BCNU and CCNU,
      against experimental rodent and murine in vivo glioma models was conducted.
      Selected articles were graded on a 15 point scale for scientific methodology. A
      stratified meta-analysis based on median-survival data and effect sizes was
      performed to generate global-efficacy estimates for BCNU and CCNU, and to produce
      'weighted-mean effect-sizes' for individual sub-categories of selected study
      characteristics. RESULTS: Fourteen papers satisfied search criteria and
      encompassed 231 treatment comparisons in 2256 animals. The median methodology
      score was 9 (range 7-12/15). Global-efficacy estimates were BCNU 0.194 (95% CI 
      0.538 to 0.927) and CCNU 0.432 (95% CI -0.392 to 1.256), with CCNU being
      significantly more effective than BCNU. Because of these wide confidence
      intervals a beneficial or detrimental effect of either agent could not be
      confirmed. Most selected study-design characteristics (e.g. glioma cell line,
      drug dosage, drug scheduling, mode of drug administration, timing of therapy
      after glioma implantation but not animal used) significantly influenced the
      efficacy-results obtained. The methodological score did not influence efficacy
      estimate. CONCLUSION: This review has found (i) experimental-design influenced
      the efficacy-data obtained and (ii) that there is highly variable outcome data
      for the efficacy of both BCNU and CCNU in experimental in vivo rodent and murine
      glioma models. In many ways these findings are analagous to the use of
      nitrosoureas in human malignant glioma. The statistically significant small
      beneficial effect of nitrosoureas in combination with other chemotherapeutic
      agents in human glioma was only noted after a meta-analysis of human randomized
      controlled trials.

PMID- 18813878
TI  - A rare cause of fatal intracranial haemorrhage.
AB  - INTRODUCTION: We report the case of a 53-year-old farmer with a 5-day history of
      severe headache, photophobia and neck stiffness. Full blood count (platelets
      173), coagulation screen were normal throughout. Liver function tests remained
      normal apart from an elevated gamma-GT (156). CT Brain was normal. CSF analysis
      showed a WCC of 454/mm(3) (60% lymphocytes), elevated CSF protein (1.42 g/l) and
      a normal CSF glucose. He was commenced on IV antibiotics and IV acyclivor and
      improved. On day 3 of admission, he complained of a sudden severe headache,
      became unresponsive (GCS 3/15). INVESTIGATIONS: CT Brain showed a massive left
      intraventricular haemorrhage. He died 4 days later. Subsequent serum serology for
      leptospirosis was positive. A repeat sample taken 4 days post-admission, showed a
      rising IgM indicating active leptospirosis. Detailed pathological examination
      confirmed intracerebral haemorrhage with normal cerebral vasculature. CONCLUSION:
      Leptospirosis is a rare cause of intracerebral haemorrhage even in the absence of
      coagulopathy.

PMID- 18813879
TI  - Quality of stroke care at an Irish Regional General Hospital and Stroke
      Rehabilitation Unit.
AB  - BACKGROUND: Robust international data support the effectiveness of stroke unit
      (SU) care. Despite this, most stroke care in Ireland are provided outside of this
      setting. Limited data currently exist on the quality of care provided. AIM: The
      aim of this study is to examine the quality of care for patients with stroke in
      two care settings-Regional General Hospital (RGH) and Stroke Rehabilitation Unit
      (SRU). METHODS: A retrospective analysis of the stroke records of consecutive
      patients admitted to the SRU between May-November 2002 and April-November 2004
      was performed applying the UK National Sentinel Audit of Stroke (NSAS) tool.
      RESULTS: The results of the study reveal that while SRU processes of care was 74%
      compliant with standards; compliance with stroke service organisational standards
      was only 15 and 43% in the RGH and SRU, respectively. CONCLUSION: The quality of
      stroke care in our area is deficient. Comprehensive reorganisation of stroke
      services is imperative.

PMID- 18813880
TI  - Fractured closed suction catheter: an unusual cause of endobronchial obstruction
      in a ventilated patient.
AB  - BACKGROUND: A 32-year-old HIV-positive man required ventilation for seizures
      secondary to viral encephalitis. He had a prolonged care unit stay and had
      percutaneous tracheostomy performed on day 14 of his admission. He subsequently
      developed persistent right basal infiltrates and atelectasis on chest radiographs
      that were slow to respond to antibiotic treatment. Fiberoptic bronchoscopy
      revealed the cause of his infiltrates to be a 14-cm tip section of closed suction
      catheter tubing that had presumably fractured during suctioning and became lodged
      in his trachea and right main bronchus. LEARNING POINT: Foreign body aspiration
      should be considered in the differential diagnosis of persisting lung infiltrates
      or atelectasis in all patients. CONCLUSION: This case describes a rare cause of
      endobronchial obstruction in a ventilated patient. Medical staff requires
      education about the importance of ensuring that suction catheters and other
      airway adjuncts are intact following use to prevent possible airway foreign
      bodies.

PMID- 18813881
TI  - Adaptive immunity to the obligate intracellular pathogen Coxiella burnetii.
AB  - Coxiella burnetii is an obligate intracellular bacterial pathogen that causes the
      zoonosis Q fever. While an effective whole-cell vaccine (WCV) against Q fever
      exists, the vaccine has limitations in being highly reactogenic in sensitized
      individuals. Thus, a safe and effective vaccine based on recombinant protein
      antigen (Ag) is desirable. To achieve this goal, a better understanding of the
      host response to primary infection and the precise mechanisms involved in
      protective immunity to C. burnetii are needed. This review summarizes our current
      understanding of adaptive immunity to C. burnetii with a focus on recent
      developments in the field.

PMID- 18813883
TI  - [The ESID Online Database for primary immunodeficiencies].

PMID- 18813882
TI  - Molecular analysis of cocaine-induced endothelial dysfunction: role of endothelin
      1 and nitric oxide.
AB  - Cocaine remains the most frequently used illicit substance. Although cocaine
      induced atherosclerosis is well documented, its mechanism of action on human
      vascular endothelial cells has not been determined. Nitric oxide (NO) and
      endothelin-1 (ET-1) are involved in endothelial cell activation and leukocyte
      recruitment. The present study monitored the effects of cocaine on NO and ET-1
      production in human aortic endothelial cells (HAECs) and the effects of sodium
      nitroprusside (SNP) and BQ-123 on leukocyte adhesion to HAECs. Acute exposure to
      cocaine (1 and 3 muM) significantly increased ET-1 production (2-fold) and ET-1
      receptor type-A (ET(A)R) protein expression, within 6-12 h. Cocaine exposure for
      a longer duration (24-72 h) showed a temporal decrease in both NO production and
      endothelial NO-synthase (eNOS) expression. The cocaine-mediated suppression of NO
      was ameliorated by co-treatment of cells with the ET(A)R blocker, BQ-123 (5 muM).
      Furthermore, both short-term (24 h) and long-term (72 h) exposure to cocaine
      increased endothelial adhesion of monocytes (U937 cells) by 20% and 40%,
      respectively, which were also suppressed by BQ-123 and SNP co-treatment. These
      data suggest that a concomitant increase in both ET-1 and ET(A)R expression in
      cocaine exposed HAECs may enhance signaling via the ET(A)R which decreases eNOS
      expression and NO production, and ultimately results in endothelial activation
      and leukocyte adhesion. Our findings implicate a molecular mechanism of action of
      cocaine and a therapeutic effect of ET(A)R-specific inhibitor in suppressing the
      cocaine-induced endothelial dysfunction.

PMID- 18813884
TI  - [The ESID Online Database for primary immunodeficiencies. First analyses with
      regard to Germany and Europe].
AB  - BACKGROUND AND METHODS: Over the past 3 years, with support by the European Union
      within the 6th Framework Programme and by the pharmaceutical industry, the ESID
      Online Database has collected data from 7,047 patients with primary
      immunodeficiencies (PIDs) in 30 countries. The system is available via a standard
      internet browser for users in registered documenting centers with their personal
      login. It comprises a common core dataset for 212 PIDs and large disease-specific
      data models for 33 diseases. These can be used for international studies on these
      cohorts. RESULTS: First analyses on the Therapy and Quality of Life section have
      shown that 42% of the registered living patients receive immunoglobulin
      replacement therapy. 76% of these receive intravenous immunoglobulins (IVIG),
      whereas 23% use the subcutaneous method of application (SCIG). In Germany,
      compared to the European figures, SCIG therapy is much more common, reaching 54%,
      whereas 46% of the patients receive IVIG. When analyzing the large cohort of
      patients with common variable immunodeficiency (CVID), patients on SCIG have less
      sick days and less days in hospital per year than those on IVIG. CONCLUSION: The
      acceptance of this new online system within Europe has been positive over the
      last few years and the database has now reached a state where it can be the basis
      for extensive international studies. However, with 551 patients, Germany only
      contributes 7.81% of the entered datasets. This is mainly due to a lack of time
      and manpower in the documenting centers and to time-consuming procedures for
      ethics approval.

PMID- 18813885
TI  - Anticoagulant and/or antiplatelet treatment in patients with atrial fibrillation
      after percutaneous coronary intervention. A single-center experience.
AB  - BACKGROUND: Atrial fibrillation (AF) is the most common cardiac arrhythmia
      sustained and frequently occurs in patients with coronary heart disease. Thus, a
      large number of patients requiring percutaneous coronary intervention (PCI) also
      suffer from AF. An anticoagulant regimen has not been standardized for patients
      with AF after coronary stent implantation. PATIENTS AND METHODS: The authors
      investigated data from 159 patients with AF who underwent PCI in their
      department. Baseline variables and incidence of a combined endpoint (stroke,
      myocardial infarction, cardiovascular death, severe bleeding) were compared in
      patients receiving clopidogrel and acetylsalicylic acid (ASA; group 1) versus
      patients receiving the combination of clopidogrel and ASA with low-molecular
      weight heparin (LMWH; group 2) versus patients receiving the combination of
      clopidogrel and ASA with oral anticoagulation (OAC; group 3) at discharge.
      RESULTS: Patients discharged with triple therapy including OAC seemed to be at
      higher risk: patients in group 3 had decreased left ventricular ejection fraction
      and increased inflammatory state as measured by plasma fibrinogen and C-reactive
      protein. Moreover, previous OAC treatment and strokes were found more often in
      this subgroup of patients. In a median follow-up of 1.4 years, two severe
      bleeding events (both in group 1), four myocardial infarctions (all in group 1),
      13 strokes (nine in group 1, four in group 2), and nine cardiovascular deaths
      (three in group 1, five in group 2, one in group 3) occurred. CONCLUSION: In this
      analysis, no treatment regimen seemed to be clearly superior. It underlines the
      importance of prospective, randomized trials to investigate the optimal
      antithrombotic/antiplatelet treatment for patients with AF after PCI.

PMID- 18813886
TI  - [Regarding the optimal hemoglobin target range in renal anemia].
AB  - Patients with chronic kidney disease (CKD) are exposed to extremely higher risks
      of atherothrombotic complications of the cardio- and cerebrovascular systems. In
      pertinent meta-analyses, overviews, editorials and comments, it has been
      considered unproven, on the basis of current data from randomized controlled
      trials, that a higher hemoglobin (Hb) value provides overall-survival benefits
      for CKD. At present, there is a "gray zone" between the intervention threshold of
      Hb < 9 g/dl and an Hb level > 13 g/dl, at which CKD is associated with a higher
      risk of cardiovascular events. This paper discusses in depth the
      hemostaseological hypothesis of increased mortality as a result of higher Hb
      levels during treatment of renal anemia with erythropoiesis-stimulating agents
      (ESA). It seems to be clearly evident that ESA activate platelets directly and
      indirectly, and that pathologically extended bleeding time is normalized when an
      Hb level of 10 g/dl is reached; from the hemostaseological perspective, a
      threshold level for treatment of renal anemia with ESA is thus defined. According
      to the present state of knowledge, an Hb target range of 10-11 g/dl seems
      reasonable for renal anemia; this is also compatible with current recommendations
      by ESA producers and the Food and Drug Administration (FDA). This target range
      avoids the upper and lower risk levels for Hb, and probably ensures a positive
      ESA effect on quality of life; it is much more cost-efficient than the target
      range of 11-12 g/dl recommended by the Kidney Disease Outcomes Quality Initiative
      (KDOQI) in 2007.

PMID- 18813887
TI  - [Cardiovascular risk assessment by primary-care physicians in Germany and its
      lack of agreement with the Established Risk Scores (DETECT)].
AB  - BACKGROUND: The concordance of several cardiovascular risk scores (PROCAM Score,
      Framingham Score and ESC Score) and its agreement with the treating physicians'
      risk assessment is unclear. METHODS: For 8,957 nationally representative primary
      care patients without known cardiovascular disease (age 40-65 years), the 10-year
      risk for experiencing a myocardial infarction or coronary death was determined by
      using various established risk scores in addition to risk prediction by the
      treating primary-care physician. RESULTS: In this sample, the mean 10-year
      coronary morbidity risk was estimated by PROCAM to be 4.9% and 10.1% by the
      Framingham Score. The mean 10-year cardiovascular mortality risk, estimated by
      the ESC Score, was 2.9%. According to the risk assessment of the primary-care
      physicians only 2.7% of the patients were assigned to this group. The number of
      patients assigned to high, medium and low risk differed substantially. Applying
      the Framingham Score, 22.6% of all patients were assigned to the high-risk group.
      Concordance in cardiovascular risk categorization between all three scores was
      present in only 34.0% of all cases. In 5.9% of the patients the three risk scores
      yielded completely different risk estimations. Only approximately 8% of the
      patients assigned to the high-risk group according to the different scores were
      also recognized as high-risk patients by the primary-care physicians. For
      approximately 48% of these patients the physician allocated a medium risk and for
      41-46% even only a low risk. CONCLUSION: The substantial level of disagreement
      between the different scores as well as of the scores with the prediction of the
      treating physicians underlines that risk stratification with the established
      scores evidently plays no significant role in routine care at this point. Which
      of the score predictions should be considered to be most sensitive and specific
      will be examined now prospectively using the 5-year prospective data of the
      DETECT study.

PMID- 18813888
TI  - [Rational diagnostics and current treatment concepts in the management of chronic
      heart failure].

PMID- 18813889
TI  - [Coincidence of coronary artery disease and takotsubo cardiomyopathy in a 72-year
      old female patient].
AB  - BACKGROUND: Takotsubo cardiomyopathy is characterized by transient left
      ventricular dysfunction in patients with normal findings on coronary angiography.
      The simultaneous incidence of coronary vessel disease and takotsubo
      cardiomyopathy is described. CASE REPORT: A 72-year-old, previously healthy
      female patient reported about chest pain. Acute emotional and physical stress
      were denied. Cardiac enzymes and electrocardiogram presented typical findings of
      myocardial infarction. Coronary angiography revealed a coronary one-vessel
      disease with occlusion of the second branch of the circumflex branch of the left
      coronary artery which did not explain the severe reduction of left ventricular
      function. After 4 months, left ventricular function and electrocardiogram had
      returned to normal. CONCLUSION: Coronary artery disease does not rule out
      takotsubo cardiomyopathy.

PMID- 18813890
TI  - [Hypophosphatemic osteomalacia].
AB  - Hypophosphatemic osteomalacia first presenting in adulthood is a rare disease. It
      is characterized by decreased serum phosphate, renal phosphate wasting, elevated
      alkaline phosphatase, and osteomalacia. The authors present a case with typical
      constellation of an oncogenic (tumor-induced) osteomalacia, the possible
      differential diagnosis, diagnostic evaluation, and complete healing after tumor
      resection. The new concepts of hereditary and acquired hypophosphatemic
      osteomalacia are discussed helping us understand this rare disease.

PMID- 18813891
TI  - Orthopaedic . Radiology . Pathology Conference: painful ulnar lesion in a 16-year
      old boy.

PMID- 18813892
TI  - Hip resurfacing arthroplasty: risk factors for failure over 25 years.
AB  - Many early metal-on-polyethylene hip resurfacing arthroplasty designs were
      abandoned after reports of high short-term and midterm failure rates. To
      investigate factors associated with failure, we retrospectively reviewed our
      experience with early-design hip resurfacing implants in 75 patients during a 25
      year period (median followup, 7.9 years; range, 0.1-25.2 years). Implant failure
      was defined as revision for any reason. One of 75 patients was lost to followup.
      The estimated rate of implant survival was 73% at 5 years, 34% at 10 years, 27%
      at 15 years, 12% at 20 years, and 8% at 25 years. Of the many clinical and
      radiographic factors considered, only age, implant type, and gender were
      associated with implant survival independent of other variables considered. Hip
      resurfacing arthroplasty showed poor overall long-term survival in this series.
      Particular attention should be paid to the identified risk factors as long-term
      followup data become available for modern designs. LEVEL OF EVIDENCE: Level IV,
      therapeutic study. See the Guidelines for Authors for a complete description of
      levels of evidence.

PMID- 18813893
TI  - MRI shows biologic restoration of posterior soft tissue repairs after THA.
AB  - Although posterior capsule repair reduces the incidence of dislocation after THA,
      radiographic imaging studies suggest a high failure rate of the repair. Using
      MRI, we prospectively followed patients to evaluate the integrity of the
      posterior soft tissue repair after primary THA. Thirty-six patients (21 men, 15
      women) underwent arthroplasty using a standard posterior approach. The posterior
      capsule and external rotators were repaired as separate layers using
      nonabsorbable sutures through two drill holes in the greater trochanter. Patients
      observed postoperative hip precautions for 6 weeks after surgery. All patients
      underwent initial MRI between postoperative Days 2 and 4. Thirty patients
      returned for followup MRI 3 months after surgery. At 3 months followup, the
      posterior capsule remained intact in 27 of 30 patients (90%) and the quadratus
      femoris repair remained intact in 29 of 30 patients (97%). Thirteen of 30
      piriformis tendon repairs (43%) and 17 conjoined tendon repairs (57%) showed a
      gap between the hypointense tendon end and the greater trochanter greater than 25
      mm. Our data show repaired posterior soft tissues provide a biologic scaffold
      allowing formation of a posterior pseudocapsule.

PMID- 18813894
TI  - Percutaneous nonviral delivery of hepatocyte growth factor in an osteotomy gap
      promotes bone repair in rabbits: a preliminary study.
AB  - Hepatocyte growth factor (HGF) was initially identified in cultured hepatocytes
      and subsequently reported to induce angiogenic, morphogenic, and antiapoptotic
      activity in various tissues. These properties suggest a potential influence of
      HGF on bone healing. We asked if gene transfer of human HGF (hHGF) into an
      osteotomy gap with a hemagglutinating virus of Japan-envelope (HVJ-E) vector
      promotes bone healing in rabbits. HVJ-E that contained either hHGF or control
      plasmid was percutaneously injected into the osteotomy gap of rabbit tibias on
      Day 14. The osteotomy gap was evaluated by radiography, pQCT, mechanical tests,
      and histology at Week 8. The expression of hHGF was evaluated by reverse
      transcriptase-polymerase chain reaction and immunohistochemistry at Week 3.
      Radiography, pQCT, and histology suggested the hHGF group had faster fracture
      healing. Mechanical tests demonstrated the hHGF group had greater mechanical
      strength. The injected tissues at 3 weeks expressed hHGF mRNA by reverse
      transcriptase-polymerase chain reaction. hHGF-positive immunohistochemical
      staining was observed in various cells at the osteotomy gap at Week 3. The data
      suggest delivery of hHGF plasmid into the osteotomy gap promotes fracture repair,
      and HGF could become a novel agent for fracture treatment.

PMID- 18813895
TI  - Midterm to long-term followup of staged reimplantation for infected hip
      arthroplasty.
AB  - Most reports on two-stage reimplantation have focused on the short-term cure rate
      of infection, but little is known about long-term reinfection-free survival or
      mechanical durability. We retrospectively reviewed 168 patients (169 hips) with
      infected arthroplasty, all of whom had two-stage reimplantation for the treatment
      of an infected total hip arthroplasty between 1988 and 1998. In the second stage,
      the femoral component was fixed with antibiotic-loaded bone cement in 121 hips;
      the remaining femoral components and all acetabular components were uncemented.
      The minimum followup time was 2 years (mean, 7 years; range, 2-16 years). At most
      recent followup, 12 hips (7.1%) were reoperated on for reinfection and 13 hips
      (7.7%) were revised for aseptic loosening or osteolysis. Apparently aseptic
      loosening occurred on one or both sides of the joint in 24 hips (14.2%). The 10
      year survivals free of reinfection and mechanical failure were 87.5% and 75.2%
      respectively. Nineteen hips dislocated and eight underwent revision surgery for
      instability. The method of femoral component fixation, either with or without
      cement, did not correlate with risk of infection, loosening, or mechanical
      failure. Based on these results, the method of fixation used for the femoral
      component during two-stage reimplantation surgery should be based on the
      surgeon's preference for fixation combined with the assessment of femoral bone
      stock. LEVEL OF EVIDENCE: Level IV, case series. See the Guidelines for Authors
      for a complete description of levels of evidence.

PMID- 18813896
TI  - [Otitis externa: etiology, diagnostic and therapy].
AB  - Otitis externa (OE) occurs during the lifetime in approximately 10% of the
      population, especially in warm and damp climates or from swimming (swimmer's
      ear). Females are most often affected around the age of 50 years and males around
      70 years of age. Both auditory canals are affected in approximately 10% of cases.
      Causes of infection are mostly bacteria, and more rarely fungi or viruses. OE can
      be accompanied not only by relatively slight pain and light swelling of the skin
      of the auditory canal, but also by severe pain, complete obstruction of the
      external meatus and retroauricular swelling. An uncomplicated infection can
      normally be treated by cleaning of the meatus by an ENT specialist and local
      application of a broad-spectrum antibiotic or an antiseptic supplemented with
      corticoids as well as antimycotics. Complicated infections, such as necrotizing
      OE, are rare and normally only occur in elderly patients with diabetes mellitus
      or in an immunosuppressed condition.

PMID- 18813898
TI  - A bee in the corridor: centering and wall-following.
AB  - In an attempt to better understand the mechanism underlying lateral collision
      avoidance in flying insects, we trained honeybees (Apis mellifera) to fly through
      a large (95-cm wide) flight tunnel. We found that, depending on the entrance and
      feeder positions, honeybees would either center along the corridor midline or fly
      along one wall. Bees kept following one wall even when a major (150-cm long) part
      of the opposite wall was removed. These findings cannot be accounted for by the
      "optic flow balance" hypothesis that has been put forward to explain the typical
      bees' "centering response" observed in narrower corridors. Both centering and
      wall-following behaviors are well accounted for, however, by a control scheme
      called the lateral optic flow regulator, i.e., a feedback system that strives to
      maintain the unilateral optic flow constant. The power of this control scheme is
      that it would allow the bee to guide itself visually in a corridor without having
      to measure its speed or distance from the walls.

PMID- 18813897
TI  - The A20 gene protects kidneys from ischaemia/reperfusion injury by suppressing
      pro-inflammatory activation.
AB  - Ischaemia followed by reperfusion (I/R) can induce inflammation and injury and is
      a risk factor for delayed graft function and rejection of transplanted kidneys.
      Inflammation is regulated by NF-kappaB transcription factors which induce pro
      inflammatory molecules in endothelial cells (EC). We examined whether A20, a
      negative regulator of NF-kappaB, can protect kidneys from I/R injury. To mimic
      the fluctuations in endothelial oxygenation that occur during I/R we exposed
      cultured human umbilical vein EC (HUVEC) to hypoxia (1% O(2) for 4 h) followed by
      re-oxygenation (21% O(2) for 1 h-24 h). We observed transient expression of pro
      inflammatory molecules (E-selectin, VCAM-1 and IL-8) and sustained expression of
      A20 in HUVEC exposed to hypoxia/re-oxygenation. The effect of A20 on endothelial
      responses to hypoxia/re-oxygenation was assessed. We observed that pre-treatment
      of HUVEC with an adenovirus containing A20 (Ad-A20) suppressed activation of NF
      kappaB and induction of pro-inflammatory molecules by hypoxia/re-oxygenation,
      whereas a control adenovirus had little or no effect. Thus the induction of A20
      may form a negative feedback loop in pro-inflammatory signalling in cells exposed
      to hypoxia/re-oxygenation. To validate our cell culture experiments we examined
      the role of A20 in renal responses to I/R. We observed that A20 was induced in
      rat kidneys exposed to I/R. Moreover, pre-treatment of animals with Ad-A20
      significantly reduced acute tubular necrosis, renal expression of VCAM-1 and NF
      kappaB activation in response to I/R, whereas pre-treatment with control
      adenovirus did not. Our observations suggest that A20 maintains physiological
      homeostasis in kidneys exposed to I/R by protecting them from inflammation and
      injury.

PMID- 18813899
TI  - [Never confuse Glenn and Blalock-Taussig again!].

PMID- 18813900
TI  - [Presaccal stenosis as a cause of epiphora].
AB  - BACKGROUND: Dacryocystographic evaluation of the location of stenoses of the
      lacrimal pathways was carried out in patients with epiphora to define the
      frequency and morphology of canalicular stenosis. PATIENTS AND METHODS: Digital
      subtraction angiography (DSA) dacryocystograms of 55 consecutive patients with
      severe epiphora and stenoses of the lacrimal draining system were reviewed in a
      consensus between three evaluators to determine radiomorphologic criteria for the
      diagnosis of canalicular stenosis. In 9 cases 3D rotational dacryocystography was
      additionally used. RESULTS: A total of 80 stenotic lesions were detected
      including 19 (24%) canalicular, 26 (32%) saccal and 35 (44%) ductal stenoses. In
      9 of the patients 3D rotational dacryocystography was used to differentiate
      between canalicular (n=4) and saccal (n=5) stenosis. Increased resistance during
      continuous injection of contrast material and lack of distension of the distal
      ductal system were the main criteria for diagnosis of canalicular stenosis.
      CONCLUSION: Presaccal stenoses accounted for nearly 25% of the stenoses found in
      this study. This type of stenosis occurs frequently and should not be overlooked
      on dacryocystography. 3D rotational dacryocystography may be helpful in unclear
      cases.

PMID- 18813901
TI  - [Radiotherapy for locally advanced prostate cancer].
AB  - Technical developments in radiation oncology have led to major improvements in
      the treatment of locally advanced prostate cancer. This article summarizes the
      publications on dose escalation, including the side effects. The effect of
      additional hormonal therapy and irradiation of the pelvic lymphatics is also
      discussed.

PMID- 18813902
TI  - [Adjuvant and neoadjuvant drug therapy for prostate cancer].
AB  - Neoadjuvant and adjuvant therapeutic strategies are widely employed for a variety
      of cancer entities. The basic aim and the potential benefit for the patient are
      to eradicate micrometastases, with the downside being side effects and
      overtreatment. Neoadjuvant and adjuvant hormone therapy for prostate cancer have
      been investigated in a number of clinical studies. Based on these studies, the
      following recommendations can be given: there is currently no indication for
      neoadjuvant therapy prior to radical prostatectomy. Adjuvant therapy using LHRH
      analogs for patients with lymph node-positive tumors following radical
      prostatectomy can be considered but should be weighed against early"biochemical
      progression triggered" treatment. For locally advanced tumors the same is true
      (bicalutamide): adjuvant treatment has shown an advantage in clinically
      progression-free survival; however, no systematic comparison is available with
      early"biochemical progression triggered" treatment. Before radiotherapy 2 months
      of neoadjuvant LHRH analog treatment has shown a survival advantage in patients
      with locally advanced tumors and a low risk of systemic spread (Gleason <7). For
      high-risk patients, long-term (2-3 years) adjuvant LHRH analog treatment is
      indicated.

PMID- 18813903
TI  - [Value of lymphadenectomy for limited nodal recurrence of prostate cancer after
      local therapy with curative intent].
AB  - After local therapy for prostate cancer, presumably isolated nodal recurrence is
      being detected in increasing numbers of patients by modern imaging techniques,
      especially by positron emission tomography (PET). The question arises whether
      lymphadenectomy may delay tumor progression.Conclusions concerning the value of
      PET/computed tomography, perioperative complications, and oncological outcome
      were derived from available studies and our own experiences. Six studies reported
      on 83 patients who underwent lymphadenectomy for suspected nodal recurrence. In
      cases with histological confirmation, no patient was cured.Hence, nodal
      recurrence in prostate cancer most likely represents a systemic affection instead
      of locally limited disease. If a drop in the prostate-specific antigen level
      occurs after lymphadenectomy, it can be assumed that the progression-free period
      is expected to be less than 12 months.The available data on oncological outcomes
      of this procedure are insufficient. Therefore, lymphadenectomy for nodal
      recurrence of prostate cancer remains an unproven approach.

PMID- 18813904
TI  - Quantitative trait locus responsible for resistance to Aphanomyces root rot
      (black root) caused by Aphanomyces cochlioides Drechs. in sugar beet.
AB  - Aphanomyces root rot, caused by Aphanomyces cochlioides Drechs., is one of the
      most serious diseases of sugar beet (Beta vulgaris L.). Identification and
      characterization of resistance genes is a major task in sugar beet breeding. To
      ensure the effectiveness of marker-assisted screening for Aphanomyces root rot
      resistance, genetic analysis of mature plants' phenotypic and molecular markers'
      segregation was carried out. At a highly infested field site, some 187 F(2) and
      66 F(3) individuals, derived from a cross between lines 'NK-310mm-O' (highly
      resistant) and 'NK-184mm-O' (susceptible), were tested, over two seasons, for
      their level of resistance to Aphanomyces root rot. This resistance was classified
      into six categories according to the extent and intensity of whole plant
      symptoms. Simultaneously, two selected RAPD and 159 'NK-310mm-O'-coupled AFLP
      were used in the construction of a linkage map of 695.7 cM. Each of nine
      resultant linkage groups was successfully anchored to one of nine sugar beet
      chromosomes by incorporating 16 STS markers. Combining data for phenotype and
      molecular marker segregation, a single QTL was identified on chromosome III. This
      QTL explained 20% of the variance in F(2) population (in the year 2002) and 65%
      in F(3) lines (2003), indicating that this QTL plays a major role in the
      Aphanomyces root rot resistance. This is the first report of the genetic mapping
      of resistance to Aphanomyces-caused diseases in sugar beet.

PMID- 18813905
TI  - The development of a PCR-based marker linked to resistance to the blackcurrant
      gall mite (Cecidophyopsis ribis Acari: Eriophyidae).
AB  - Gall mite (Cecidophyopsis ribis) is the most serious pest of blackcurrant (Ribes
      nigrum L.), causing the damaging condition known as 'big bud' and also
      transmitting blackcurrant reversion virus (BRV) within and between plantations.
      The identification of resistant germplasm is at present a time-consuming and
      expensive process, dependent on field infestation plots. Resistance based on gene
      Ce introgressed from gooseberry has been used in UK breeding programmes for
      blackcurrant. Using a bulked segregant analysis, 90 AFLP primer combinations were
      screened and a linkage map constructed around the resistance locus controlled by
      Ce. Sixteen of the primer combinations produced a fragment in the resistant
      bulked progeny and the gall mite-resistant parent, but not in the susceptible
      bulked progeny and parent; subsequent testing on individual progeny identified an
      AFLP fragment closely linked to gall mite resistance. This fragment, designated
      E41M88-280, was converted to a PCR-based marker based on sequence-specific
      primers, amplifying only in resistant individuals. Validation of this marker
      across a range of susceptible and resistant blackcurrant germplasm with different
      genetic backgrounds confirmed its reliability in the identification of mite
      resistant germplasm containing gene Ce. The conversion of an AFLP fragment to a
      sequence-based PCR marker simplifies its application and therefore increases its
      utility for selection of mite-resistant germplasm in high-throughput breeding
      programmes for blackcurrant.

PMID- 18813906
TI  - High resolution genetic and physical mapping of the I-3 region of tomato
      chromosome 7 reveals almost continuous microsynteny with grape chromosome 12 but
      interspersed microsynteny with duplications on Arabidopsis chromosomes 1, 2 and
      3.
AB  - The tomato I-3 gene introgressed from the Lycopersicon pennellii accession LA716
      confers resistance to race 3 of the fusarium wilt pathogen Fusarium oxysporum f.
      sp. lycopersici. We have improved the high-resolution map of the I-3 region of
      tomato chromosome 7 with the development and mapping of 31 new PCR-based markers.
      Recombinants recovered from L. esculentum cv. M82 x IL7-2 F2 and (IL7-2 x IL7-4)
      x M82 TC1F2 mapping populations, together with recombinants recovered from a
      previous M82 x IL7-3 F2 mapping population, were used to position these markers.
      A significantly higher recombination frequency was observed in the (IL7-2 x IL7
      4) x M82 TC1F2 mapping population based on a reconstituted L. pennellii
      chromosome 7 compared to the other two mapping populations based on smaller
      segments of L. pennellii chromosome 7. A BAC contig consisting of L. esculentum
      cv. Heinz 1706 BACs covering the I-3 region has also been established. The new
      high-resolution map places the I-3 gene within a 0.38 cM interval between the
      molecular markers RGA332 and bP23/gPT with an estimated physical size of 50-60
      kb. The I-3 region was found to display almost continuous microsynteny with grape
      chromosome 12 but interspersed microsynteny with Arabidopsis thaliana chromosomes
      1, 2 and 3. An S-receptor-like kinase gene family present in the I-3 region of
      tomato chromosome 7 was found to be present in the microsyntenous region of grape
      chromosome 12 but was absent altogether from the A. thaliana genome.

PMID- 18813907
TI  - [Complications related to implants in arthroscopic shoulder surgery].
AB  - With the increase in shoulder arthroscopies are increased complications related
      to shoulder implants frequently used for arthroscopic rotator cuff repair and
      shoulder stabilisation. The biggest problem is malpositioning of the suture
      anchor, which might lead to persistent pain, serious cartilage damage, decreased
      range of motion, and failure of the reconstruction, resulting in revision
      surgery. Especially in osteoporotic bone, it is important to choose an implant
      that provides sufficient mechanical strength. Other possible complications are
      related to the sutures of the anchor. Suture damage or accidental removal of the
      sutures from the anchor could leave them useless in situ. Tangling of the
      sutures, especially in massive reconstructions of the rotator cuff, can lead the
      surgeon to switch to an open technique. Compared with metal implants,
      bioabsorbable implants have advantages concerning possible revision surgery.
      However, implant costs, anchor hole enlargement, and possible higher failure
      rates compared with metallic implants should be considered. A rare but serious
      complication is allergic reaction to the implant.

PMID- 18813908
TI  - [C-reactive protein. An independent risk factor for the development of infection
      after primary arthroplasty].
AB  - BACKGROUND: Infection is a severe complication after primary arthroplasty of the
      hip (THA) or knee joint (TKA). Based on its high sensitivity, the C-reactive
      protein (CRP) concentration has become a valuable tool in the diagnosis of
      infection, although it has only moderate specificity. Because of this, it remains
      unclear whether a preoperative increased CRP without clinical symptoms is a risk
      factor for infection after primary arthroplasty. MATERIAL AND METHODS: In a
      retrospective analysis, we investigated individuals with infection after primary
      THA or TKA and matched them with patients without infection after similar
      operations. Matching criteria were age, gender, and present diseases. The average
      age of the 50 included individuals was 67.4 (range 48-81) years, with eight men
      and 17 women in each group. In addition to preoperative CRP, specific patient and
      surgery data and microbiological and histopathologic findings were obtained.
      RESULTS: The average preoperative CRP concentration in the infected patient group
      was 1.3+/-2.5 mg/dl, in contrast to 0.4+/-0.7 mg/dl in the noninfected group. A
      threshold of 0.5 mg/dl was appropriate for discriminating between the two groups
      [13/25 (52%) in the infection group vs. 3/25 (12%) in the control group,
      p=0.003]. Independent from the patient group, CRP concentrations were
      significantly increased in individuals with diabetes mellitus (1.2+/-1.5 vs.
      0.7+/-2.0 mg/dl, p=0.03). CONCLUSION: An increased preoperative CRP concentration
      without clinical findings of infection is a risk factor for prosthetic infection
      after primary THA or TKA with a threshold concentration of 0.5 mg/dl. Latent
      local or systemic infections or aseptic inflammation with subsequent local immune
      suppression seem to be responsible. We recommend evaluating CRP before every THA
      and TKA. For values beyond 0.5 mg/dl, an exploration for infection should be
      done. Otherwise, the patient should be informed about the increased risk of
      infection.

PMID- 18813909
TI  - [Aspects of finger mobility].
AB  - The movements of the finger, centrally induced and controlled via open or closed
      loops, need the simultaneous action of several muscles and muscle groups. In this
      way, rigid differentiation between antagonists and synergists is functionally
      abolished. Synchronous flexion and extension of a finger needs not only a palmar
      flexion and a dorsal extension motor system but also a third oblique running
      motor system. This is given by the interosseous-lumbricalis system. Opposition
      and repositioning of the thumb require muscle configuration other than that
      provided by the other fingers.

PMID- 18813910
TI  - Physiotherapy does not prevent, or hasten recovery from, ventilator-associated
      pneumonia in patients with acquired brain injury.
AB  - OBJECTIVE: To investigate the effect of respiratory physiotherapy on the
      prevention and treatment of ventilator-associated pneumonia (VAP) for adults in
      an intensive care unit (ICU) with an acquired brain injury (ABI). DESIGN AND
      SETTING: Two-part, prospective, randomised controlled trial. PATIENTS: A total of
      144 subjects with ABI admitted with a Glasgow Coma Scale </=9, requiring
      intracranial pressure monitoring, and invasive mechanical ventilation (MV) for
      >24 h; 33 subjects were subsequently diagnosed with VAP. INTERVENTION:
      Respiratory physiotherapy comprised six treatments (positioning, manual
      hyperinflation and suctioning) in each 24-h period whilst on MV. The Control
      Group received standard medical/nursing care but no respiratory physiotherapy.
      MEASUREMENTS AND RESULTS: There were no significant differences between groups
      for incidence of VAP, duration of MV, length of ICU stay or clinical variables
      such as requirement for re-ventilation. CONCLUSIONS: In adults with ABI, regular
      respiratory physiotherapy in addition to routine medical/nursing care does not
      appear to prevent VAP, reduce length of MV or ICU stay. Due to small numbers, it
      is not possible to draw any conclusions as to whether or not respiratory
      physiotherapy hastens recovery from VAP.

PMID- 18813912
TI  - Microcirculation and multi-organ failure in patients with sepsis.

PMID- 18813913
TI  - Time dependent decrease in blood glucose levels after sampling potentially
      affects intensive insulin therapy in the intensive care unit.

PMID- 18813914
TI  - Individual contribution of metabotropic glutamate receptor (mGlu) 2 and 3 to c
      Fos expression pattern evoked by mGlu2/3 antagonism.
AB  - OBJECTIVES AND MATERIALS AND METHODS: The aims of the present study were (1) to
      determine the neuronal activation pattern elicited by the group II mGlu
      antagonist LY341495 and (2) to evaluate the contribution of each group II mGlu
      subtype by using wild-type (WT) and knockout (KO) mice lacking either mGlu2 or
      mGlu3. c-Fos expression was used as a marker of neuronal activation. RESULTS AND
      DISCUSSION: In WT mice, LY341495 induced widespread c-Fos expression in 68 out of
      92 brain areas, including limbic areas such as the amygdala, septum, prefrontal
      cortex, and hippocampus. LY341495-induced c-Fos response was markedly decreased
      in the medial part of the central amygdala (CeM) and lateral septum (LS) in mGlu3
      KO mice, as well as in the lateral parabrachial nucleus (LPB) in both KO strains.
      In the majority of investigated areas, LY341495-induced c-Fos expression was
      similar in KO and WT mice. Analysis of the cellular and subcellular distribution
      of mGlu2 and mGlu3 revealed a prevailing presence of mGlu3-immunoreactivity in
      the CeM in glial processes and in postsynapstic neuronal elements, whereas only
      rare presynaptic axon terminals were found immunoreactive for mGlu2. CONCLUSION:
      In conclusion, our data indicate that group II mGlu blockade increases neuronal
      activation in a variety of brain areas, including many stress- and anxiety
      related areas. The activation of two key brain areas, the CeM and LS, is mediated
      via mGlu3, while activation in the LPB involves both subtypes. Moreover, in the
      majority of investigated areas, LY341495-mediated neuronal activation appears to
      require a complex cross talk between group II mGlu subtypes or the action of
      LY341495 on additional receptors.

PMID- 18813915
TI  - Separation of Amadori peptides from their unmodified analogs by ion-pairing RP
      HPLC with heptafluorobutyric acid as ion-pair reagent.
AB  - Glycation is a common class of nonenzymatic posttranslational modifications
      relevant for several diseases and cell aging in general, such as D: -glucose
      derived modifications at the epsilon-amino groups of lysine residues in blood
      proteins, especially albumin, immunoglobulin, and hemoglobin, for diabetic
      patients. These Amadori compounds are identified on the peptide level after
      enzymatic digestion and chromatographic separation by mass spectrometry. Their
      syntheses usually rely on a global glycation approach. Both areas require the
      reliable separation of glycated peptides from their unmodified congeners present
      in different ratios, which is typically not achieved by standard eluent systems
      in ion-pairing RP-HPLC (IP-RPLC). Here, we compare aqueous acetonitrile and
      methanol gradients containing either trifluoroacetic acid (TFA) or
      heptafluorobutyric acid (HFBA) as ion-pairing agents to separate such peptide
      pairs. TFA-containing eluents resulted in rather low resolutions, and the
      glycated and unglycated peptides often coeluted. HFBA increased the retention
      times of the unmodified peptide more than for the glycated peptide thereby
      improving the separation of all eight studied peptide pairs, even achieving
      baseline separations for some sequences. Thus the use of HFBA as ion-pair reagent
      provides a universally applicable eluent system in IP-RPLC to separate glycated
      peptides from their unmodified counterparts, even at the preparative scale
      required for synthetic peptides.

PMID- 18813916
TI  - Somatoparaphrenia: a body delusion. A review of the neuropsychological
      literature.
AB  - A review of published brain-damaged patients showing delusional beliefs
      concerning the contralesional side of the body (somatoparaphrenia) is presented.
      Somatoparaphrenia has been reported, with a few exceptions, in right-brain
      damaged patients, with motor and somatosensory deficits, and the syndrome of
      unilateral spatial neglect. Somatoparaphrenia, most often characterized by a
      delusion of disownership of left-sided body parts, may however occur without
      associated anosognosia for motor deficits, and personal neglect. Also
      somatosensory deficits may not be a core pathological mechanism of
      somatoparaphrenia, and visual field disorders may be absent. Deficits of
      proprioception, however, may play a relevant role. Somatoparaphrenia is often
      brought about by extensive right-sided lesions, but patients with posterior
      (parietal-temporal), and insular damage are on record, as well as a few patients
      with subcortical lesions. Possible pathological factors include a deranged
      representation of the body concerned with ownership, mainly right-hemisphere
      based, and deficits of multisensory integration. Finally, the rubber hand
      illusion, that brings about a bodily misattribution in neurologically unimpaired
      participants, as somatoparaphrenia does in brain-damaged patients, is briefly
      discussed.

PMID- 18813917
TI  - Spatial and temporal aspects of muscle hyperalgesia induced by nerve growth
      factor in humans.
AB  - Intramuscular injection of nerve growth factor (NGF) has been shown to induce
      long-term sensitisation and time-dependent hyperalgesia indicating potential
      involvement of both central and peripheral pain mechanisms. This double-blind
      placebo-controlled study was designed to describe the spatial distribution of
      muscle hyperalgesia over time (immediately after, 3 h, 1, 4, 7 and 21 days) after
      injecting NGF (5 mug) into the tibialis anterior (TA) muscle, to explore possibly
      involved central pain mechanisms and to investigate the effect of gender on
      development of hyperalgesia. Totally 20 healthy volunteers (10 men and 10 women)
      participated in the study. An isotonic saline injection into the contralateral TA
      muscle served as a control condition for the NGF injection. Pressure pain
      thresholds (PPT) were used to test for muscle hyperalgesia along the TA (seven
      sites) muscle at the extensor digitorum longus and at the web between 1st and 2nd
      metatarsal (central involvement). One day after the NGF/control injections,
      hypertonic saline (0.5 ml, 5.8%) was injected into the left and right TA to study
      the pain response to chemical stimulation of the hyperalgesic muscle tissue.
      Scores on a modified Likert scale were used to assess soreness during muscle
      function. An area of hyperalgesia was observed locally at the injected site 3 h
      after injection of NGF, which expanded both proximally and distally on day 1;
      this effect subsided on day 4. Decreased PPT was also found between 1st and 2nd
      metatarsal on day 1. Hypertonic saline evoked more pain in men when injected in
      the NGF treated TA compared to the control leg. Injection of NGF increased muscle
      soreness during muscle activity for 7 days. In this material there was no gender
      effect of NGF-induced muscle hyperalgesia. The expansion of muscle hyperalgesia
      to distant areas indicates that central mechanisms are involved.

PMID- 18813918
TI  - CT utilization: the emergency department perspective.
AB  - CT scan utilization in the pediatric emergency department (ED) has dramatically
      increased in recent years. This likely reflects the improved diagnostic
      capability of CT, as well as its wider availability. However, the utility of CT
      is tempered by the high radiation exposure to patients as well as cost. In this
      review we will consider the magnitude of changes in CT use in the pediatric ED,
      and we will examine some of the driving forces behind these increases. In
      addition, we will consider strategies to limit growth in CT scan utilization or
      even result in reductions in CT use in the future. These strategies include
      better physician and patient education, application of existing clinical decision
      rules to reduce CT utilization and development of new rules, technical
      alterations in CT protocols to reduce per-exam exposures, use of alternative
      imaging modalities such as US and MRI that do not expose patients to ionizing
      radiation, and expanded use of clinical observation in place of immediate
      diagnostic imaging. Reform of liability laws might alleviate another driving
      force behind high CT utilization rates. Protocols must be designed to maximize
      patient safety by limiting radiation exposures while preserving rapid and
      accurate diagnosis of time-sensitive conditions.

PMID- 18813919
TI  - Proteolysis of prion protein by cathepsin S generates a soluble beta-structured
      intermediate oligomeric form, with potential implications for neurotoxic
      mechanisms.
AB  - Formation of PrP aggregates is considered to be a characteristic event in the
      pathogenesis of TSE diseases, accompanied by brain inflammation and
      neurodegeneration. Factors identified as contributing to aggregate formation are
      of interest as potential therapeutic targets. We report that in vitro proteolysis
      of ovine PrP(94-233) (at neutral pH and in the absence of denaturants) by the
      protease cathepsin S, a cellular enzyme that also shows enhanced expression in
      pathogenic conditions, occurs selectively in the region 135-156. This results in
      an unusually efficient, concentration-dependent conformational conversion of a
      large subfragment of PrP(94-233) into a soluble beta-structured oligomeric
      intermediate species, that readily forms a thioflavin-T-positive aggregate. N
      terminal sequencing of the proteolysis fragments shows the aggregating species
      have marked sequence similarities to truncated PrP variants known to confer
      unusually severe pathogenicity when transgenically expressed in PrP(o/o) mice.
      Circular dichroism analysis shows that PrP fragments 138-233, 144-233 and 156-233
      are significantly less stable than PrP(94-233). This implies an important
      structural contribution of the beta1 sequence within the globular domain of PrP.
      We propose that the removal or detachment of the beta1 sequence enhances beta
      oligomer formation from the globular domain, leading to aggregation. The cellular
      implications are that specific proteases may have an important role in the
      generation of membrane-bound, potentially toxic, beta-oligomeric PrP species in
      pre-amyloid states of prion diseases. Such species may induce cell death by
      lysis, and also contribute to the transport of PrP to neuronal targets with
      subsequent amplification of pathogenic effects.

PMID- 18813920
TI  - Isolation and structural characterisation of two antibacterial free fatty acids
      from the marine diatom, Phaeodactylum tricornutum.
AB  - One solution to the global crisis of antibiotic resistance is the discovery of
      novel antimicrobial compounds for clinical application. Marine organisms are an
      attractive and, as yet, relatively untapped resource of new natural products.
      Cell extracts from the marine diatom, Phaeodactylum tricornutum, have
      antibacterial activity and the fatty acid, eicosapentaenoic acid (EPA), has been
      identified as one compound responsible for this activity. During the isolation of
      EPA, it became apparent that the extracts contained further antibacterial
      compounds. The present study was undertaken to isolate these additional
      antibacterial factors using silica column chromatography and reverse-phase high
      performance liquid chromatography. Two antibacterial fractions, each containing a
      pure compound, were isolated and their chemical structures were investigated by
      mass spectrometry and nuclear magnetic resonance spectroscopy. The antibacterial
      compounds were identified as the monounsaturated fatty acid (9Z)-hexadecenoic
      acid (palmitoleic acid; C16:1 n-7) and the relatively unusual polyunsaturated
      fatty acid (6Z, 9Z, 12Z)-hexadecatrienoic acid (HTA; C16:3 n-4). Both are active
      against Gram-positive bacteria with HTA further inhibitory to the growth of the
      Gram-negative marine pathogen, Listonella anguillarum. Palmitoleic acid is active
      at micro-molar concentrations, kills bacteria rapidly, and is highly active
      against multidrug-resistant Staphylococcus aureus. These free fatty acids warrant
      further investigation as a new potential therapy for drug-resistant infections.

PMID- 18813921
TI  - Directed evolution of aniline dioxygenase for enhanced bioremediation of aromatic
      amines.
AB  - The objective of this study was to enhance the activity of aniline dioxygenase
      (AtdA), a multi-component Rieske non-heme iron dioxygenase enzyme isolated from
      Acinetobacter sp. strain YAA, so as to create an enhanced biocatalyst for the
      bioremediation of aromatic amines. Previously, the mutation V205A was found to
      widen the substrate specificity of AtdA to accept 2-isopropylaniline (2IPA) for
      which the wild-type enzyme has no activity (Ang EL, Obbard JP, Zhao HM, FEBS J,
      274:928-939, 2007). Using mutant V205A as the parent and applying one round of
      saturation mutagenesis followed by a round of random mutagenesis, the activity of
      the final mutant, 3-R21, was increased by 8.9-, 98.0-, and 2.0-fold for aniline,
      2,4-dimethylaniline (24DMA), and 2-isopropylaniline (2IPA), respectively, over
      the mutant V205A. In particular, the activity of the mutant 3-R21 for 24DMA,
      which is a carcinogenic aromatic amine pollutant, was increased by 3.5-fold over
      the wild-type AtdA, while the AN activity was restored to the wild-type level,
      thus yielding a mutant aniline dioxygenase with enhanced activity and capable of
      hydroxylating a wider range of aromatic amines than the wild type.

PMID- 18813922
TI  - Quantitative analysis of isoprenoid diphosphate intermediates in recombinant and
      wild-type Escherichia coli strains.
AB  - In biotechnology, the heterologous biosynthesis of isoprenoid compounds in
      Escherichia coli is a field of great interest and growth. In order to achieve
      higher isoprenoid yields in heterologous E. coli strains, it is necessary to
      quantify the pathway intermediates and adjust gene expression. In this study, we
      developed a precise and sensitive nonradioactive method for the simultaneous
      quantification of the isoprenoid precursors farnesyl diphosphate (FPP) and
      geranylgeranyl diphosphate (GGPP) in recombinant and wild-type E. coli cells. The
      method is based on the dephosphorylation of FPP and GGPP into the respective
      alcohols and involves their in situ extraction followed by separation and
      detection using gas chromatography-mass spectrometry. The integration of a
      geranylgeranyl diphosphate synthase gene into the E. coli chromosome leads to the
      accumulation of GGPP, generating quantities as high as those achieved with a
      multicopy expression vector.

PMID- 18813923
TI  - Effect of bulk liquid BOD concentration on activity and microbial community
      structure of a nitrifying, membrane-aerated biofilm.
AB  - Membrane-aerated biofilms (MABs) are an effective means to achieve nitrification
      and denitrification of wastewater. In this research, microsensors, fluorescence
      in situ hybridization (FISH), and modeling were used to assess the impact of bulk
      liquid biological oxygen demand (BOD) concentrations on the activity and
      microbial community structure of nitrifying MABs. With 1 g m(-3) BOD in the bulk
      liquid, the nitrification rate was 1.3 g N m(-2) day(-1), slightly lower than the
      1.5 g N m(-2) day(-1) reported for no bulk liquid BOD. With bulk liquid BOD
      concentrations of 3 and 10 g m(-3), the rates decreased to 1 and 0.4 g N m(-2)
      day(-1), respectively. The percent denitrification increased from 20% to 100%
      when the BOD increased from 1 to 10 g m(-3) BOD. FISH results indicated
      increasing abundance of heterotrophs with increasing bulk liquid BOD, consistent
      with the increased denitrification rates. Modeling was used to assess the effect
      of BOD on nitrification rates and to compare an MAB to a conventional biofilm.
      The model-predicted nitrification rates were consistent with the experimental
      results. Also, nitrification in the MAB was much less sensitive to BOD inhibition
      than the conventional biofilm. The MAB achieved concurrent nitrification and
      denitrification, whereas little denitrification occurred in the conventional
      biofilm.

PMID- 18813924
TI  - Construction of an Aspergillus oryzae cell-surface display system using a
      putative GPI-anchored protein.
AB  - A novel cell-surface display system was constructed in Aspergillus oryzae. Each
      of the five genes encoding the putative cell-wall-localized protein from the A.
      oryzae genome was cloned and these cell-surface anchor functions were examined by
      fusion to the C-terminal of the green fluorescent protein (GFP). Using the MP1
      and CWP proteins as anchor proteins, GFP signals were strongly observed on the
      cell surface of recombinant A. oryzae. When these proteins were used as anchor
      proteins for cell-surface display of beta-glucosidase from A. oryzae, enzyme
      activity was detected on the cell surface. In particular, beta-glucosidase
      activity of recombinant A. oryzae using MP1, a putative
      glycosylphosphatidylinositol (GPI) anchor protein was higher than CWP. Based on
      these results, it was concluded that the MP1 protein can act as a GPI-anchor
      protein in A. oryzae, and the proposed cell-surface display system using MP1
      allows for the display of heterogeneous and endogenous proteins.

PMID- 18813927
TI  - A multi-center phase II study of S-1 plus paclitaxel as first-line therapy for
      patients with advanced or recurrent unresectable gastric cancer.
AB  - PURPOSE: This study was conducted to evaluate the safety and efficacy of S-1 and
      paclitaxel combination therapy for patients with advanced gastric cancer.
      METHODS: Eligible patients had previously untreated advanced or relapsed gastric
      cancer with measurable lesion(s) and an ECOG PS of 0-2. Treatment consisted of S
      1 35 mg/m(2) p.o. b.i.d. on days 1-14 followed by a 7-day off plus paclitaxel 70
      mg/m(2) i.v. on days 1 and 8 of a 21-day cycle. RESULTS: Fifty-six patients (M/F
      = 37/19) were enrolled. The median age was 59 years. The median number of cycles
      administered was six (range 1-18). Out of the 53 patients evaluated, there was 1
      (1.9%) CR, 20 (37.7%) confirmed PRs, 5 (9.4%) unconfirmed PRs, 21 (39.6%) SDs,
      and 6 (11.3%) PDs. The objective tumor response was 39.6%. The median time to
      progression was 29 weeks. The median survival was 51 weeks. All 56 patients were
      assessed for treatment safety. The treatment was well tolerated with grade 3/4
      neutropenia in 20%/13%, grade 3 febrile neutropenia in 7%, grade 2/3 diarrhea in
      9%/4%, vomiting in 11%/0%, stomatitis in 4%/4%, and neuropathy in 4%/0% of
      patients. CONCLUSIONS: S-1 and paclitaxel combination treatment is an effective
      regimen with a favorable toxicity profile in patients with advanced gastric
      cancer.

PMID- 18813928
TI  - The effect of temperature on Natural Antisense Transcript (NAT) expression in
      Aspergillus flavus.
AB  - Naturally occurring Antisense Transcripts (NATs) compose an emerging group of
      regulatory RNAs. These regulatory elements appear in all organisms examined, but
      little is known about global expression of NATs in fungi. Analysis of currently
      available EST sequences suggests that 352 cis NATs are present in Aspergillus
      flavus. An Affymetrix GeneChip microarray containing probes for these cis NATs,
      as well as all predicted genes in A. flavus, allowed a whole genome expression
      analysis of these elements in response to two ecologically important temperatures
      for the fungus. RNA expression analysis showed that 32 NATs and 2,709 genes were
      differentially expressed between 37 degrees C, the optimum temperature for
      growth, and 28 degrees C, the conducive temperature for the biosynthesis of
      aflatoxin (AF) and many other secondary metabolites. These NATs correspond to
      sense genes with diverse functions including transcription initiation,
      carbohydrate processing and binding, temperature sensitive morphogenesis, and
      secondary metabolism. This is the first report of a whole genome transcriptional
      analysis of NAT expression in a fungus.

PMID- 18813929
TI  - Less disease severity and favorable prognosis are associated with postmenopausal
      systemic lupus erythematosus patients.
AB  - The aim of this study is to characterize the clinical manifestations of
      postmenopausal systemic lupus erythematosus (SLE) patients. Of the 699 SLE
      inpatients, 20 postmenopausal and 70 menstruous SLE patients were evaluated and
      compared for the clinical manifestations. The mean age of onset was 55.05 years
      (range from 42 to 66) with a peak of 50-60 in postmenopausal lupus patients. The
      average time from SLE onset to diagnosis was 2.18 years. Arthritis was the most
      frequent initial manifestation in the postmenopausal group. Other common clinical
      manifestations and laboratory abnormalities include lassitude, fever, alopecia,
      malar rash, cardiac impairment and weight loss, and elevated ESR, decreased C3,
      ANA >or= 1:80, hypergammaglobulinemia and anti-RNP antibody positive. Compared
      with menstruous lupus patients, postmenopausal patients were more likely to have
      weight loss (P < 0.01), myalgia and myasthenia (P < 0.01), and less likely to
      have malar rash (P < 0.05), renal involvement (P < 0.01), leukocytopenia (P <
      0.05) and positive ANA (P < 0.01). Thus, less disease severity and favorable
      prognosis were associated with postmenopausal SLE patients. Misdiagnosis and
      missed diagnosis were easy to make with their non-specific symptoms with fewer
      features suggestive of diagnosis.

PMID- 18813930
TI  - Intracellular calcium responses to cholinergic stimulation of lymphocytes from
      healthy donors and patients with rheumatoid arthritis.
AB  - This study was performed to identify the role of cholinergic stimulation on
      changes of intracellular calcium concentrations as intracellular messenger of
      neuroimmune interaction. Incubation of PBMC with acetylcholine (ACh) leads to
      Ca(2+) oscillations in healthy controls. PBMC from rheumatoid arthritis (RA)
      patients exhibited increased basal Ca(2+) concentrations with a significantly
      reduced capacity to respond upon ACh stimulation compared to healthy controls. It
      can be assumed that cholinergic signals in PBMC are mediated via the nicotinergic
      type of ACh receptors, causing changes in intracellular Ca(2+) concentrations
      with various types of oscillations. The significantly decreased modulation of
      intracellular Ca(2+) levels by ACh in PBMC of RA patients points further to a
      disturbed neuroimmune interaction in this chronic disease.

PMID- 18813931
TI  - Proteins prenylated by type I protein geranylgeranyltransferase act positively on
      the jasmonate signalling pathway triggering the biosynthesis of monoterpene
      indole alkaloids in Catharanthus roseus.
AB  - In Catharanthus roseus, the first step of monoterpenoid indole alkaloids (MIA)
      biosynthesis results from the condensation of the indole precursor tryptamine
      with the terpenoid precursor secologanin. Secologanin biosynthesis requires two
      successive biosynthetic pathways, the plastidial methyl-D: -erythritol 4
      phosphate (MEP) pathway and the monoterpene secoiridoid pathway. In C. roseus
      cell culture, the expression of several genes encoding enzymes of these two
      pathways is dramatically down-regulated by auxin, while strongly enhanced by
      cytokinin and methyl-jasmonate. Furthermore, our previous studies have shown that
      protein prenylation events are also involved in the transcriptional activation of
      some of these genes. In the present work, we investigate the involvement of
      protein prenylation in the jasmonate signalling pathway leading to MIA
      biosynthesis. Inhibition of protein prenyltransferase down-regulates the methyl
      jasmonate-induced expression of MEP and monoterpene secoiridoid pathway genes and
      thus abolishes MIA biosynthesis. Jointly, it also inhibits the methyl-jasmonate
      induced expression of the AP2/ERF transcription factor ORCA3 that acts as a
      central regulator of MIA biosynthesis. Finally, a specific silencing of protein
      prenyltransferases mediated by RNA interference in C. roseus cells shows that
      inhibition of type I protein geranylgeranyltransferase (PGGT-I) down-regulates
      the methyl-jasmonate-induced expression of ORCA3, suggesting that PGGT-I
      prenylated proteins are part of the early steps of jasmonate signalling leading
      to MIA biosynthesis.

PMID- 18813932
TI  - Visualisation of intracerebral haemorrhage with flat-detector CT compared to
      multislice CT: results in 44 cases.
AB  - The aim of the study was to test the reliability of intracerebral haemorrhage
      (ICH) detection with C-arm-mounted flat-detector computed tomography (FD-CT) in
      the angio suite as compared to multislice CT (MSCT). In this study 44 patients
      with 45 ICH were included. All patients were investigated with MSCT and FD-CT
      during angiographic evaluation. As a control group we included 16 patients
      without ICH. In each haematoma we assessed volumetric data of the ICH and counted
      the numbers of ICH-positive slices. Using interobserver ratings, we additionally
      investigated the potential of FD-CT to serve as a diagnostic tool to detect ICH.
      In FD-CT three haematomas were not detected because of motion and beam-hardening
      artefacts in the region close to the skull base. The r value for the degree of
      interobserver agreement for the number of slices was 0.95 for MSCT and 0.94 for
      FD-CT. Measurements of the area and the calculated volume of the ICH showed high
      inter- and intraobserver agreement. Our results indicate that FD-CT is a helpful
      tool in the daily emergency management of ICH patients as detection of ICH was
      found to be nearly as reliable as in MSCT. Limitations of this technology are
      motion and beam-hardening artefacts that may mask small haematomas located in the
      posterior fossa or the skull base.

PMID- 18813933
TI  - Magnetic resonance imaging of the cervical spine: comparison of 2D T2-weighted
      turbo spin echo, 2D T2*weighted gradient-recalled echo and 3D T2-weighted
      variable flip-angle turbo spin echo sequences.
AB  - To compare an isotropic three-dimensional (3D) high-resolution T2-weighted (w) MR
      sequence and its reformations with conventional sequences for imaging of the
      cervical spine. Fifteen volunteers were examined at 1.5 T using sagittal and
      axial 3D T2-w, sagittal and axial 2D T2w, and axial 2D T2*w MR sequences. Axial
      reformations of the sagittal 3D dataset were generated (3D MPR T2w). Signal-to
      noise and image homogeneity were evaluated in a phantom and in vivo. Visibility
      of ten anatomical structures of the cervical spine was evaluated. Artifacts were
      assessed. For statistical analysis, Cohen's kappa, Wilcoxon matched pairs, and t
      testing were utilized. There were no significant differences in homogeneity
      between the sequences. Sagittal 3D T2w enabled better delineation of nerve roots,
      neural foramina, and intraforaminal structures compared to sagittal 2D T2w. Axial
      3D T2w and axial 3D MPR T2w resulted in superior visibility of most anatomical
      structures compared to axial 2D T2w and comparable results to 2D T2*w concerning
      the spinal cord, nerve roots, intraforaminal structures, and fat. Artifacts were
      most pronounced in axial 2D T2w and axial 3D T2w. Acquisition of a 3D T2w data
      set is feasible in the cervical spine with superior delineation of anatomical
      structures compared to 2D sequences.

PMID- 18813934
TI  - Active surveillance for prostate cancer: trials and tribulations.
AB  - INTRODUCTION: Prostate specific antigen (PSA) screening results in the detection
      of prostate cancer in many men who are not destined to die from the disease. This
      often results in overtreatment. One approach to reducing the overtreatment effect
      is to treat selectively by observing patients with favorable risk disease, and
      treating only the subsets who are reclassified as higher risk over time, based on
      biochemical or pathologic progression of disease. METHODS: The data supporting
      the active surveillance concept is reviewed, including the results of several
      large-scale Phase 2 studies. A number needed to treat analysis was performed
      based on these studies and a large randomized trial of radical prostatectomy
      versus watchful waiting. The arguments in favor of, and opposed to, active
      surveillance are presented. RESULTS: The largest, most mature Phase 2 study of
      active surveillance has reported an 85% overall survival and 99% disease-specific
      survival with a median follow-up of 8 years (range 2-11 years). The number needed
      to treat analysis suggests that between 80 and 100 radical prostatectomies would
      be required for each prostate cancer death avoided in a favorable risk, screen
      detected population. CONCLUSION: Active surveillance appears to be safe for
      favorable risk prostate cancer and represents an appealing alternative to radical
      treatment for all newly diagnosed men. Further follow-up and a randomized study
      design are required to conclusively demonstrate the safety of this approach over
      the 15- to 20-year time frame. A large-scale randomized trial has recently been
      initiated internationally to address this question.

PMID- 18813935
TI  - Responses to acute and chronic desiccation stress in Enchytraeus (Oligochaeta:
      Enchytraeidae).
AB  - Enchytraeids are small soil living oligochaete worms with high sensitivity to low
      soil moisture. The effects of acute and chronic desiccation on survival and
      reproduction were determined in Enchytraeus albidus and Enchytraeus crypticus.
      Further, effects of acute drought stress on the water balance physiology and
      accumulation of osmolytes were investigated in E. albidus. Survival of E.
      crypticus and E. albidus was significantly influenced by exposure time.
      Reproduction was much more sensitive to desiccation than survival and was
      significantly reduced from -0.06 bar, which was surprising because no dehydration
      or change in the body fluid osmolality of E. albidus occurred until much harsher
      drought regimes occurred. The body fluid osmolality of E. albidus was relatively
      high, about 500 mOsm. Congruent with this no water loss or changes in osmotic
      pressure occurred until equivalent or higher water potential values of the
      environment were reached. Two osmolytes, glucose and alanine, were up-regulated
      in drought exposed E. albidus. Even though enchytraeids display moderate
      physiological protection to rapid changes in soil moisture (by having a high
      osmotic pressure) in the short term, populations subjected to long-term drought
      stress can be severely reduced even under moderate drought levels.

PMID- 18813936
TI  - Endoscopic third ventriculostomy: the best option in the treatment of persistent
      hydrocephalus after posterior cranial fossa tumour removal?
AB  - BACKGROUND: Ten to 40% of children operated on for a posterior fossa tumour
      require a further surgical procedure for the management of a persisting active
      ventricular dilation. The management of this kind of hydrocephalus is still
      controversial. OBJECTIVE: To prospectively evaluate the effectiveness of post
      operative endoscopic third ventriculostomy (ETV) in the management of persistent
      active hydrocephalus in a series of children operated on for a posterior cranial
      fossa tumour. METHODS: The management protocol consisted of: (1) placement of a
      peri-operative antibiotic impregnated external ventricular catheter (Bactiseal)
      and tumour removal, (2) post-operative intracranial pressure (ICP) monitoring
      through the external ventricular drainage, (3) ETV in case of persistent
      ventricular dilation and persistently abnormal high ICP values and (4)
      ventriculoperitoneal shunt implantation in case of ETV failure. RESULTS: Thirty
      on a total of 104 children (28.8%) operated on between January 2001 and February
      2007 at our institution needed a further surgical treatment for the persistence
      of the hydrocephalus after the removal of their posterior cranial fossa tumour.
      They were sub-divided in two groups according to the early (group 1--21 patients)
      or later (group 2--nine patients) definition of the persistence of an active
      ventricular dilation based on clinical, radiological and ICP monitoring data. ETV
      was successful in 90.0% of the patients in the present series (27/30 patients),
      without statistically significant differences among the two groups considered.
      CONCLUSIONS: Post-operative ETV should be considered the best option to treat
      persistent hydrocephalus after the removal of posterior fossa tumours.

PMID- 18813937
TI  - Transitional cell carcinoma of the bladder in first decade of life.
AB  - This report describes two rare cases of well-differentiated, non-invasive
      transitional cell carcinomas in children (Grade 1 Stage pTa). One was 8-year-old
      girl with a polypoid lesion and the other 9-year-old girl with kissing bilateral
      paraureteral lesions. The initial presentation was haematuria and symptoms of
      urinary tract infection. Subsequent course and investigation confirmed the
      diagnosis. Complete resection of the lesion and follow-up with urine cytology,
      vesical ultrasound and check cystoscopy at 4 years has showed no evidence of
      recurrence.

PMID- 18813938
TI  - Giant malignant ovarian fibrothecoma involved with retroperitoneal structures
      mimicking a retroperitoneal sarcoma.
AB  - INTRODUCTION: Ovary is located inside peritoneal cavity. However, a huge
      malignant ovarian tumor may get involved with retroperitoneal structures. CASE
      REPORT: We reported a case of a 70-year-old woman presented with a 2-month
      history of increased abdominal distention and was subsequently found to have a
      giant abdominal mass. A huge low signal intensity mass with the involvement of
      retroperitoneal structures was showed on MRI. At operation, we found that the
      tumor pushed mesentery and small bowel upwards with the encasement of 10 cm
      jejunum and was fixed posteriorly to vena cava, aorta, right iliac vessels, and
      right ureter. It was dissected from the retroperitoneal structures and resected
      en bloc with the involved jejunum. CONCLUSION: Although ovary is located inside
      peritoneal cavity, a huge malignant ovarian tumor may get involved with
      retroperitoneal structures. So, great care should be taken not to injury the
      retroperitoneal structures as vena cava, mesenteric vessels, iliac vessels, and
      ureters.

PMID- 18813939
TI  - Assignment of unknown persons to their geographical origin by determination of
      stable isotopes in hair samples.
AB  - Analysing the isotope ratio of light elements in human tissue of an unknown
      person helps to reconstruct the life history with regard to geographical origin
      and/or typical food supply. In this study the isotope ratios of the bio-elements
      in hair samples of 111 persons from 13 different countries all over the world
      were measured with the aim of provenance determination. The results indicated
      that individuals from Costa Rica and Brazil can be differentiated from typical
      European individuals by delta(13)C, Australians by delta(34)S and delta(2)H in
      hair samples. The combination and evaluation of the data by multivariate
      statistical analysis considerably improved origin assignment. Investigation of
      hair samples from a number of individuals from one particular region (southern
      Germany) yielded remarkable variation of isotopic values indicating different
      nutritional habits. The possibilities and limitations of this method in its
      current state are demonstrated and discussed.

PMID- 18813940
TI  - Sex determination from buccal mucosa scrapes.
AB  - Establishing individuality is an imperative aspect in any investigation
      procedure. At times, it becomes necessary to determine the sex of the individual
      to establish identity, and saliva stains found at the scene of crime are of major
      help in such cases. In the present study, we have determined the sex of the
      individual from buccal mucosal scrapings. Buccal smears prepared from 100 men and
      100 women were stained by the Papanicolaou staining method. Cells were observed
      for Barr bodies under oil immersion with a compound microscope, and the
      percentage of Barr-body-positive cells was determined. It was observed that 1.14%
      of buccal mucosal cells in men (range = 0-4%) and 39.29% of buccal mucosal cells
      in women (range = 20-78%) showed Barr bodies. Inferences from the study show that
      the presence of Barr body in buccal mucosal cells can be demonstrated with a fair
      degree of accuracy using Papanicolaou staining. The sex of the individual can be
      determined accurately, as two non-overlapping ranges for the percentage of Barr
      body-positive cells has been obtained for men and women. This method not only
      proves to be accurate but is also simple and economic.

PMID- 18813941
TI  - No effect of carbohydrate feeding on 16 km cycling time trial performance.
AB  - The aim of this study is to investigate the effects of CHO ingestion during high
      intensity exercise performance lasting approximately 25 min. Twelve endurance
      trained male cyclists (age 19-41 years; body mass 73.2 +/- 4.2 kg; VO(2)max 66.4
      +/- 6.2 ml kg(-1) min(-1)) completed a simulated 16 km time trial (457 +/- 37 kJ)
      time trial in the lab on three occasions. Once they received a 6% carbohydrate
      electrolyte solution (CHO) and twice they received the same electrolyte
      containing placebo drink (PLA). Carbohydrate or placebo drinks were ingested 5
      min before the start (4 ml kg(-1)) and at 25, 50, and 75% of completion of the
      time trial (1.4 ml kg(-1)). The CHO drink was a 6% sucrose-glucose-electrolyte
      solution. No differences were observed in the time to complete the time trials
      with either treatment. Time in min:s were 25:30 +/- 1:34 and 25:27 +/- 1:46 for
      the two placebo trials and 25:38 +/- 1:59 in the CHO trial. Power output during
      the time trials was also remarkably similar: 300 +/- 37 W, 301 +/- 39 W and 299
      +/- 40 W, respectively. Pacing strategies and heart rate were identical in all
      three trials. From the two placebo trials, a coefficient of variation for this
      performance task was calculated to be 1.1%. Data from this study provides
      evidence that carbohydrate ingestion during short high intensity exercise
      (approximately 30 min, 85-90% VO(2)max) does not improve performance.
      Furthermore, this study found a very low coefficient of variation (1.1%) for a
      simulated 16 km time trial.

PMID- 18813942
TI  - Interacting with an artificial partner: modeling the role of emotional aspects.
AB  - In this paper we introduce a simple model based on probabilistic finite state
      automata to describe an emotional interaction between a robot and a human user,
      or between simulated agents. Based on the agent's personality, attitude, and
      nature, and on the emotional inputs it receives, the model will determine the
      next emotional state displayed by the agent itself. The probabilistic and time
      varying nature of the model yields rich and dynamic interactions, and an
      autonomous adaptation to the interlocutor. In addition, a reinforcement learning
      technique is applied to have one agent drive its partner's behavior toward
      desired states. The model may also be used as a tool for behavior analysis, by
      extracting high probability patterns of interaction and by resorting to the
      ergodic properties of Markov chains.

PMID- 18813943
TI  - Evolution of DNA-methylation machinery: DNA methyltransferases and methyl-DNA
      binding proteins in the amphioxus Branchiostoma floridae.
AB  - DNA methylation is an epigenetic mark associated with gene regulation and cell
      memory, silencing of transposable elements, genomic imprinting, and repression of
      spurious transcription of duplicated sequences. These roles have varied widely
      during animal evolution and current functions depend on the specific methylation
      pattern of the species under consideration. The patterns of methylation are
      established, maintained, and translated into appropriate functional states by the
      DNA-methylation machinery, which includes three groups of methyltransferase
      enzymes, Dnmt1, Dnmt2 and Dnmt3, and five methyl-DNA binding proteins, Mbd1,
      Mbd2, Mbd3, Mbd4, and MeCP2. In this study, I have identified the members of the
      Dnmt and the Mbd gene families in the cephalochordate amphioxus (Branchiostoma
      floridae), the most basal extant chordate and one of the closest sister groups of
      vertebrates. Database searches, phylogenetic studies and protein domain analyses
      revealed the presence of the three major groups of Dnmt enzymes in the
      cephalochordate genome, whereas only two Mbd members, Mbd2/3 and Mbd4, were
      found. Analysis of the amphioxus methylation machinery suggested that the
      complexity and the structural organization of cephalochordate methyltransferases
      do not differ substantially from those of current vertebrate enzymes, while new
      Mbd proteins arose in vertebrates, which perhaps minimized certain collateral
      effects associated with the major genomic changes that occurred during the
      invertebrate-vertebrate transition.

PMID- 18813944
TI  - Integrin-linked kinase cytoplasmic and nuclear expression in laryngeal
      carcinomas.
AB  - Integrin-linked kinase (ILK) has been implicated in the development and
      progression of several human malignancies. Previous in vitro studies also
      implicate ILK in the activation of Akt and beta-catenin as well as in the
      regulation of E-cadherin expression. However, the role of ILK in human laryngeal
      cancer and its possible in vivo downstream effectors in the disease are currently
      unknown. We examined by immunohistochemistry the protein expression of ILK,
      phosphorylated-Akt (p-Akt), E-cadherin, and beta-catenin in 97 invasive squamous
      laryngeal carcinomas. Increased cytoplasmic and nuclear expression of ILK and p
      Akt decreased membranous expression of E-cadherin and nuclear accumulation of
      beta-catenin was found in 87.6%, 85.6%, 71.1%, and 43.3% of cases, respectively.
      Our results suggest that ILK expression may be implicated in human laryngeal
      carcinoma and its localization in the nucleus possibly proposes novel nuclear
      functions of this molecule. In addition, enhanced ILK expression correlates with
      activation of Akt but not with downregulation of E-cadherin and activation of
      beta-catenin. Finally, in our material while activated Akt seems to characterize
      well-differentiated tumors, loss of E-cadherin and activation of beta-catenin
      correlated with high grade carcinomas.

PMID- 18813945
TI  - CD34(+) fibrocytes in melanocytic nevi and malignant melanomas of the skin.
AB  - CD34(+) fibrocytes are constitutive elements of the human connective tissue. The
      stroma associated with invasive carcinomas is characterized by a stereotypic loss
      of CD34(+) fibrocytes and a phenotype change towards CD34(-) alpha-Smooth muscle
      actin (SMA)(+) myofibroblasts. Secreted protein acidic and rich in cysteine
      (SPARC) is an important mediator of tumor-associated stromal remodeling.
      Melanocytic lesions of the skin have not been investigated as to this aspect up
      to now. Thus, we investigated a total of 20 malignant melanomas and 29
      melanocytic nevi. The normal dermis and benign melanocytic nevi showed numerous
      CD34(+) fibrocytes, whereas malignant melanomas were devoid of this cell type.
      alpha-SMA-positive myofibroblasts were absent from the normal dermis, melanocytic
      nevi, and malignant melanomas. SPARC was positive in malignant melanoma cells and
      negative in their associated stroma, while all melanocytic nevi were completely
      negative. The stromal phenotype of malignant melanomas (CD34(-) alpha-SMA(-))
      differs from that of invasive carcinomas (CD34(-) alpha-SMA(+)) suggesting
      different pathogenic mechanisms involved in tumor-associated stromal remodeling.
      SPARC expression appears to be closely related to malignancy in melanocytic
      lesions.

PMID- 18813946
TI  - Intratumoural lymphatics in benign and malignant soft tissue tumours.
AB  - Soft tissue sarcomas do not generally metastasise via lymphatics, and the
      presence or absence of lymphatic vessels within sarcomas and benign soft tissue
      tumours is not known. In this study, we determined whether lymphatic vessels were
      present in a wide range of benign and malignant soft tissue lesions by examining
      intratumoural expression of the lymphatic endothelial cell markers, Lyve-1 and
      podoplanin. Intratumoural Lyve-1+/podoplanin+ lymphatics were not identified in
      sarcomas apart from all cases of epithelioid sarcoma (a tumour which is known to
      metastasise to lymph nodes) and a few cases of leiomyosarcoma, rhabdomyosarcoma
      and synovial sarcoma. Intratumoural lymphatics were also absent in most benign
      soft tissue tumours. Reparative and inflammatory soft tissue lesions contained
      lymphatics, as did all (pseudosarcomatous) proliferative myofibroblastic lesions
      including nodular, proliferative and ischaemic fasciitis, elastofibroma, nuchal
      fibroma and deep fibromatosis. Our results show that most soft tissue sarcomas do
      not contain intratumoural lymphatics, a finding which is consistent with the
      infrequent finding of sarcoma metastasis to lymph nodes. In contrast to
      fibrosarcoma and a number of other malignant spindle cell tumours, proliferative
      fibroblastic/myofibroblastic lesions of soft tissue contain intralesional
      lymphatic vessels.

PMID- 18813947
TI  - First experiences with intraoperative Levosimendan in pediatric cardiac surgery.
AB  - Levosimendan is a calcium-sensitizing agent with effective inotropic properties.
      It has been shown to improve cardiac function, hemodynamic performance, and
      survival in adults with severe heart failure. However, the effect of Levosimendan
      in pediatric cardiac surgery has not yet been investigated. Thus, we report on
      our experience with the intraoperative application of Levosimendan in seven
      infants (body weight range 2.6-6.3 kg) with severe myocardial dysfunction after
      complex congenital heart surgery. During the administration of Levosimendan, the
      heart rate, mean arterial blood pressure, and central venous pressure did not
      change. The mean arterial lactate level significantly decreased 24 and 48 h after
      the first infusion compared to baseline. Central venous oxygen saturation
      increased significantly 24 and 48 h after the onset of Levosimendan infusion. We
      found intraoperatively administered Levosimendan to be well tolerated in the
      seven infants with severe myocardial dysfunction after complex congenital heart
      surgery. Levosimendan is a new rescue drug which has beneficial effects, even in
      pediatric cardiac surgery.

PMID- 18813948
TI  - Biochemical monitoring of pregnancy and breast feeding in five patients with
      classical galactosaemia--and review of the literature.
AB  - Pregnancy, delivery, and postpartal metabolic control was monitored biochemically
      in five patients (22-38 years of age) with clinically, enzymatically, and
      genotypically established classical galactosaemia and good dietary compliance.
      Three of the patients performed breast feeding of their newborns. Monitoring
      parameters were galactose-1-phosphate and galactitol concentrations in
      erythrocytes and urinary excretion of galactose, galactitol, galactonate, and
      lactose. During pregnancy, a small but steady increase of renal metabolite
      excretion rates was observed. After delivery, a moderate transient increase of
      metabolite concentrations with peak values within the first week post partum
      occurred, irrespective of breast feeding. Altogether, there was no evidence for
      clinically or subclinically significant changes of metabolic control during
      pregnancy, delivery, or lactation. In conclusion, a specific metabolic monitoring
      is apparently not required in pregnant galactosemic women, and breast feeding of
      the nongalactosemic offspring can be recommended.

PMID- 18813949
TI  - Rapid development of life-threatening complete atrioventricular block in Kearns
      Sayre syndrome.
AB  - Kearns-Sayre syndrome is a rare mitochondrial disorder with defined diagnostic
      criteria. Knowledge of these diagnostic criteria and early diagnosis are
      important to ensure periodic electrocardiograms for identification of cardiac
      conduction disorders, which are the most important prognostic factor of the
      disease. We report on a 9-year-old girl with rapid development of a life
      threatening complete atrioventricular block within 10 months and discuss the
      importance and time interval of regular electrocardiograms. Our patient survived
      by placing a temporary transvenous pacemaker lead followed by permanent pacemaker
      implantation a few days later.

PMID- 18813950
TI  - Age-associated differences in prevalence of group A streptococcal type-specific M
      antibodies in children.
AB  - Our prior studies of the molecular epidemiology of group A streptococcus (GAS)
      pharyngitis indicated that the most common emm types associated with pediatric
      pharyngitis in North America were 12, 1, 28, and 4. We previously reported that
      the proportions of pediatric pharyngitis due to emm types 12 and 4 decreased with
      increasing age throughout childhood. We hypothesized that this is due to age
      associated acquisition of antibodies to the amino-terminal type-specific region
      of common GAS M proteins during childhood. We sought to demonstrate this in sera
      from healthy children by using ELISAs for M 12, 1, 28, and 4. Enzyme-linked
      immunosorbent assays (ELISA) using chemically synthesized peptides copying amino
      terminal type-specific regions of the M proteins were performed on sera from four
      age groups of healthy children (group I: 3-6 years, group II: 7-10 years, group
      III: 11-14 years, group IV: 15-18 years). ELISA data were correlated with
      opsonophagocytic assays for a subset of sera and M 1 GAS. Sera from healthy 12-20
      month-old children were used as negative controls. Our results showed that the
      highest percentage of positivity was for M12, which also showed progressive
      seropositivity in older children. For the other serotypes, the highest
      seroprevalence rates were in the 11-14-year-old age group. The presence of ELISA
      antibodies against M1 correlated with opsonophagocytic activity, a previously
      studied indicator of immunologic protection.

PMID- 18813951
TI  - Identification of SLC26A4 gene mutations in Iranian families with hereditary
      hearing impairment.
AB  - Mutations in the SLC26A4 gene at the DFNB4 locus are responsible for Pendred
      syndrome and non-syndromic hereditary hearing loss (DFNB4). This study included
      80 nuclear families with two or more siblings segregating presumed autosomal
      recessive hearing loss. All deaf persons tested negative for mutations in GJB2 at
      the DFNB1 locus and were, therefore, screened for autozygosity by descent (ABD)
      using short tandem repeat polymorphisms (STRPs) that flanked SLC26A4. In 12
      families, homozygosity for STRPs suggested possible ABD in this genomic region.
      Affected individuals in five families had a positive perchlorate discharge test.
      Sequence analysis of SLC26A4 identified ten mutations in eight families (T420I,
      1197delT, G334V, R409H, T721M, R79X, S448L, L597S, 965insA and L445W), of which,
      four are novel (T420I, G334V, 965insA and R79X). These results imply that Pendred
      syndrome is the most prevalent form of syndromic hereditary hearing loss in Iran.

PMID- 18813952
TI  - Epidermal growth factor receptor status and persistent activation of Akt and
      p44/42 MAPK pathways correlate with the effect of cetuximab in head and neck and
      colon cancer cell lines.
AB  - OBJECTIVE: The aim of this study was to investigate the effect of epidermal
      growth factor receptor (EGFR) blockade on cell survival and on downstream
      signalling pathways using the monoclonal antibody cetuximab. METHODS: We used
      three colon cancer cell lines, of which one was EGFR-negative, and two head and
      neck squamous cell carcinoma (HNSCC) lines. EGFR expression and gene copy number
      were measured by immunohistochemistry and FISH analysis, respectively. The effect
      of cetuximab, irradiation or the combination of both on cell growth was estimated
      by SRB assay. Western blotting was used to determine the phosphorylation of
      intracellular signalling proteins and cell cycle phase distribution was measured
      by flow cytometry. RESULTS: The addition of cetuximab had only limited effects on
      cell growth, with a maximum inhibition of approximately 30%, but was correlated
      with the amount of protein expression and gene copy number of EGFR. When combined
      with irradiation, the effect of cetuximab was only additive and not dependent on
      the inherent radio-sensitivity of the cell lines. Persistent phosphorylation of
      Akt and/or p44/42 MAPK was detected by western blot in all of the cell lines,
      whereas there was no phosphorylation of Jak2 or STAT3. CONCLUSIONS: None of these
      factors alone could predict the sensitivity to cetuximab. Rather, the results
      suggest that it might be necessary to determine the activation status of several
      intracellular signalling proteins to better predict the sensitivity to cetuximab
      treatment.

PMID- 18813953
TI  - Association of loss of BRCA1 expression with centrosome aberration in human
      breast cancer.
AB  - PURPOSE: Centrosome aberration in number and/or size is reportedly often observed
      in human breast cancer. The aim of this study was to investigate the relationship
      between centrosome aberration and chromosomal instability as well as the
      expression of centrosome regulators such as BRCA1, Aurora-A, and p53. METHODS:
      Centrosome aberration in number and size was determined immunohistochemically
      using the anti-gamma-tubulin antibody, and chromosomal instability was evaluated
      by fluorescence in situ hybridization analysis of chromosomes 1, 11, and 17 in
      paraffin sections from 50 human breast cancers. Immunohistochemical examination
      of BRCA1, Aurora-A, and p53 was also performed to examine the relationship of
      their expression with centrosome aberration. RESULTS: Percentage of tumor cells
      with centrosome aberration in size varied from 0.9 to 30.4% (median 9.5%) and in
      number it varied from 0.5 to 86.5% (median 34.5%) in each tumor. No significant
      association in number or size, however, was observed between chromosomal
      instability and centrosome aberration. Numerical centrosome aberration was
      significantly associated with negative BRCA1 expression (P = 0.001). Breast
      tumors (n = 3) from patients with a proven BRCA1 germline mutation also showed a
      significant relationship with numerical centrosome aberration (P = 0.011). On the
      other hand, expression of Aurora-A or p53 was not significantly associated with
      centrosome aberration in either number or size. CONCLUSIONS: Centrosome
      aberration is not associated with chromosomal instability, indicating the
      importance of other mechanisms in the induction of chromosomal instability in
      human breast cancer. BRCA1, but not Aurora-A and p53, is significantly involved
      in the pathogenesis of centrosome aberration.

PMID- 18813954
TI  - Systematic sequence analysis and identification of tissue-specific or stress
      responsive genes of NAC transcription factor family in rice.
AB  - NAM, ATAF, and CUC (NAC) transcription factors comprise a large plant-specific
      gene family and a few members of this family have been characterized for their
      roles in plant growth, development, and stress tolerance. In this study,
      systematic sequence analysis revealed 140 putative NAC or NAC-like genes (ONAC)
      in rice. Phylogenetic analysis suggested that NAC family can be divided into five
      groups (I-V). Among them, all the published development-related genes fell into
      group I, and all the published stress-related NAC genes fell into the group III
      (namely stress-responsive NAC genes, SNAC). Distinct compositions of the putative
      motifs were revealed on the basis of NAC protein sequences in rice. Most members
      contained a complete NAC DNA-binding domain and a variable transcriptional
      regulation domain. Sequence analysis, together with the organization of putative
      motifs, indicated distinct structures and potential diverse functions of NAC
      family in rice. Yeast one-hybrid analysis confirmed that 12 NAC proteins
      representing different motif compositions can bind the NAC core DNA-binding site.
      Real-time polymerase chain reaction (PCR) analysis revealed 12 genes with
      different tissue-specific (such as callus, root, stamen, or immature endosperm)
      expression patterns, suggesting that these genes may play crucial regulatory
      roles during growth and development of rice. The expression levels of this family
      were also checked under various abiotic stresses including drought, salinity, and
      low temperature. A preliminary check based on our microarray data suggested that
      more than 40 genes of this family were responsive to drought and/or salt
      stresses. Among them, 20 genes were further investigated for their stress
      responsiveness in detail by real-time PCR analysis. Most of these stress
      responsive genes belonged to the group III (SNAC). Considering the fact that a
      very limited number of genes of the NAC family have been characterized, our data
      provide a very useful reference for functional analysis of this family in rice.

PMID- 18813955
TI  - Systematic analysis of NPK1-like genes in rice reveals a stress-inducible gene
      cluster co-localized with a quantitative trait locus of drought resistance.
AB  - Phosphorylation by protein kinase is a ubiquitous key mechanism in translating
      external stimuli such as drought stress. NPK1 is a mitogen-activated protein
      kinase kinase kinase identified in Nicotiana tabacum and plays important roles in
      cytokinesis and auxin signaling transduction and responses to multiple stresses.
      Here we report the evolution, structure, and comprehensive expression profile of
      21 NPK1-like genes in rice (Oryza sativa L.). Phylogenetic analysis of NPK1-like
      sequences in rice (OsNPKL), Arabidopsis, and other plants reveals that NPK1-like
      genes could be classified into three subgroups. Three OsNPKL gene clusters,
      located on chromosome 1 (OsNPKL1, 2, 3, and 4), 5 (OsNPKL14 and 15), and 10
      (OsNPKL19 and 20), respectively, were identified in the rice genome. These
      clustered genes, which most likely evolved by tandem gene duplication, belong to
      the same phylogenetic subgroup, with similar genomic structures and conserved
      motifs in the kinase domain, which is unique to this subgroup. Expression
      analysis of OsNPKL genes under abiotic stresses suggests that the stress
      responsive genes are mainly from the same subgroup. Especially interesting is
      that all the clustered genes are induced by drought, salt, or cold stress, and a
      few members are very strongly induced by drought. Some of the clustered genes are
      also induced by abscisic acid. The gene cluster on chromosome 1 is co-located
      with a quantitative trait locus (QTL) related to drought resistance. Although the
      drought-induced expression levels of the four genes in the cluster show no
      difference between the two parents used for QTL mapping, sequence variation in
      coding regions of the genes between the parents has provided some clues for
      further functional characterization of this gene cluster in abiotic stress
      tolerance in rice.

PMID- 18813956
TI  - BAC end sequences corresponding to the B4 resistance gene cluster in common bean:
      a resource for markers and synteny analyses.
AB  - In common bean, a complex disease resistance (R) gene cluster, harboring many
      specific R genes against various pathogens, is located at the end of the linkage
      group B4. A BAC library of the Meso-american bean genotype BAT93 was screened
      with PRLJ1, a probe previously shown to be specific to the B4 R gene cluster,
      leading to the identification of 73 positive BAC clones. BAC-end sequencing (BES)
      of the 73 positive BACs generated 75 kb of sequence. These BACs were organized
      into 6 contigs, all mapped at the B4 R gene cluster. To evaluate the potential of
      BES for marker development, BES-derived specific primers were used to check for
      linkage with two allelic anthracnose R specificities Co-3 and Co-3 ( 2 ), through
      the analysis of pairs of Near Isogenic Lines (NILs). Out of 32 primer pairs
      tested, two revealed polymorphisms between the NILs, confirming the suspected
      location of Co-3 and Co-3 ( 2 ) at the B4 cluster. In order to identify the
      orthologous region of the B4 R gene cluster in the two model legume genomes, bean
      BESs were used as queries in TBLASTX searches of Medicago truncatula and Lotus
      japonicus BAC clones. Putative orthologous regions were identified on chromosome
      Mt6 and Lj2, in agreement with the colinearity observed between Mt and Lj for
      these regions.

PMID- 18813957
TI  - Toxicity of reduced nitrogen in eelgrass (Zostera marina) is highly dependent on
      shoot density and pH.
AB  - In sheltered, eutrophicated estuaries, reduced nitrogen (NHx), and pH levels in
      the water layer can be greatly enhanced. In laboratory experiments, we studied
      the interactive effects of NHx, pH, and shoot density on the physiology and
      survival of eelgrass (Zostera marina). We tested long-term tolerance to NHx at pH
      8 in a 5-week experiment. Short-term tolerance was tested for two shoot densities
      at both pH 8 and 9 in a 5-day experiment. At pH 8, eelgrass accumulated nitrogen
      as free amino acids when exposed to high loads of NHx, but showed no signs of
      necrosis. Low shoot density treatments became necrotic within days when exposed
      to NHx at pH 9. Increased NH3 intrusion and carbon limitation seemed to be the
      cause of this, as intracellular NHx could no longer be assimilated. Remarkably,
      experiments with high shoot densities at pH 9 showed hardly any necrosis, as the
      plants seemed to be able to alleviate the toxic effects of high NHx loads through
      joint NHx uptake. Our results suggest that NHx toxicity can be important in
      worldwide observed seagrass mass mortalities. We argue that the mitigating effect
      of high seagrass biomass on NHx toxicity is a positive feedback mechanism,
      potentially leading to alternative stable states in field conditions.

PMID- 18813958
TI  - Sex ratio variation and mixed pairs in roe deer: evidence for control of sex
      allocation?
AB  - Sex allocation has provided rich ground for the development of evolutionary
      theory. The dominant models in vertebrates have provided predictions of sex ratio
      based on asymmetry in variance in breeding success between sexes in the breeding
      system, and the relative effect of local competition. In ungulates, empirical
      work has provided some support for these models, but has also generated
      apparently contradictory observations. Recent models have provided some
      predictions for both individual and population sex ratio, showing that the
      availability of high-quality habitat patches and dispersal rates can critically
      affect both population- and individual-level expectations. We explore patterns in
      offspring sex ratio among a large sample of roe deer, a species with some
      interesting aspects of the breeding system. We found that in singleton
      pregnancies (the minority) there was an excess of male embryos, which was more
      marked in does in good condition at most sites. While the sex ratio among twins
      was close to parity, and unaffected either by average condition among populations
      or by individual condition within populations, we observed a clear excess of
      mixed pregnancies (sub-binomial variance, SBV). The excess was greater where the
      average condition was high. Within sites, population changes in average condition
      were associated with changes in SBV: in populations declining in condition, SBV
      also declined. There was no tendency for mixed twins to be more likely in
      individuals in better condition within a population. We conclude that condition
      dependent allocation of sex does occur in roe deer. We suggest that in these
      "income breeders", mixed pairs might offer the greatest opportunity to optimize
      maternal investment during lactation, when conditions will be unpredictable, and
      that this is increasingly the case when average condition is poor.

PMID- 18813959
TI  - New data on ectomycorrhizae and soils of the Chinese truffles Tuber
      pseudoexcavatum and Tuber indicum, and their impact on truffle cultivation.
AB  - Chinese truffles serve as a good complement to the market for Tuber melanosporum
      (Perigord black truffle). However, Chinese truffles could be introduced
      accidentally or fraudulently into the plantations of Mediterranean truffles, and
      they could have a negative effect on truffle production and natural ecosystems.
      The study of Tuber species from China which are commercialized in Europe began 14
      years ago. Tuber pseudoexcavatum was proposed as a new species, and this has been
      validated by some authors based on molecular and phylogenetic studies. We
      synthesize their ectomycorrhizae using samples from the type collection, and we
      compare T. pseudoexcavatum and Tuber indicum ectomycorrhizae. The ectomycorrhizae
      of these species have a morphology which is related to the ectomycorrhizae of T.
      melanosporum. We provide useful information for the rapid screening of the above
      mentioned Chinese truffles ectomycorrhizae, for the quality control of commercial
      plants mycorrhized with Tuber. Moreover, we analyze the soil tolerance and the
      host plant affinity of T. pseudoexcavatum and T. indicum, in order to assess the
      capacity of both Chinese truffles to penetrate T. melanosporum plantations and
      habitats.

PMID- 18813960
TI  - Ganglioneurocytoma of the spinal cord: report of a case and review of literature.
AB  - A case of ganglioneurocytoma of the spinal cord in a 51-year-old man is reported.
      Patient presented with a progressively worsening back pain and hyposthenia of
      lower limbs. Magnetic resonance imaging of the spinal cord revealed an intradural
      lesion in the T10-11 spinal segments, hyperintense on T1-weighted sequences.
      Complete resection was achieved. The patient did not show evidence of recurrence
      12 months after surgery. On histology, the lesion was composed of round to oval
      cells with fine granular, slightly eosinophilic to clear cytoplasm suggesting a
      neurocytic differentiation. Some ganglion cells were observed. Neither
      significant cytologic atypia nor mitoses were present. The neoplastic cells were
      strongly positive with synaptophysin and negative with glial fibrillary acid
      protein. Neurocytomas are uncommon tumors typically arising within the lateral
      ventricles near the foramen of Monro. Extraventricular neurocytomas have been
      reported at various sites with rare examples in spinal cord. In the present
      paper, a case of ganglioneurocytoma of the spinal cord is reported with review of
      literature and discussion of differences compared to neurocytomas of other sites.

PMID- 18813961
TI  - Back and hip extensor muscles fatigue in healthy subjects: task-dependency effect
      of two variants of the Sorensen test.
AB  - Paraspinal muscle fatigability during various trunk extension tests has been
      widely investigated by electromyography (EMG), and its task-dependency is
      established recently. Hip extensor muscle fatigability during the Sorensen test
      has been reported. The aim of the present experiments was to evaluate the task
      dependency of back and hip extensor muscle fatigue during two variants of the
      Sorensen test. We hypothesized that the rate of muscular fatigue of the hip and
      back extensor muscles varies according to the test position. Twenty healthy young
      males with no history of low back pain volunteered to participate in this cross
      sectional study. They were asked to perform two body weight-dependent isometric
      back extension tests (S1 = Sorensen test; S2 = modified Sorensen on a 45 degrees
      Roman chair). Surface EMG activity of the paraspinal muscles (T10 and L5 levels)
      and hip extensor muscles (gluteus maximus; biceps femoris) was recorded, and
      muscular fatigue was assessed through power spectral analysis of the EMG data by
      calculating the rate of median power frequency change. We observed hip extensor
      muscle fatigue simultaneously with paraspinal muscle fatigue during both Sorensen
      variants. However, only L5 level EMG fatigue indices showed a task-dependency
      effect between S1 and S2. Hip extensor muscles appear to contribute to load
      sharing of the upper body mass during both Sorensen variants, but to a different
      extent because L5 level fatigue differs between the Sorensen variants. Our
      findings suggest that task-dependency has to be considered when EMG variables are
      compared between two types of lumbar muscle-fatiguing tasks.

PMID- 18813963
TI  - Iatrogenic arteriovenous fistula of the superficial temporal artery.
AB  - INTRODUCTION: The temporal artery courses superficially over the temporal bone
      and thus can be vulnerable to trauma. Although traumatic lacerations of this
      vessel are indeed common, trauma-induced arteriovenous fistulae involving the
      temporal artery are relatively rare. Arteriovenous fistulae caused by iatrogenic
      injury to the temporal artery are rarer still. DISCUSSION AND CONCLUSION: We
      report a case of an ateriovenous fistula involving the superficial temporal
      artery which developed after surgical repair of trauma to the vessel following a
      blunt head injury. Ultimately, the lesion was successfully treated with complete
      excision.

PMID- 18813964
TI  - Alzheimer's disease risk variants show association with cerebrospinal fluid
      amyloid beta.
AB  - The use of quantitative endophenotypes in genetic studies may provide greater
      power, allowing for the use of powerful statistical methods and a biological
      model for the effects of the disease-associated genetic variation. Cerebrospinal
      fluid (CSF) amyloid beta (Abeta) levels are promising endophenotypes for late
      onset Alzheimer's disease (LOAD) and show correlation with LOAD status and Abeta
      deposition. In this study, we investigated 29 single nucleotide polymorphisms
      (SNPs) positive in AlzGene ( http://www.alzgene.org ) meta-analyses, for
      association with CSF Abeta levels in 313 individuals. This study design makes it
      possible to replicate reported LOAD risk alleles while contributing novel
      information about the mechanism by which they might affect that risk. Alleles in
      ACE, APOE, BDNF, DAPK1, and TF are significantly associated with CSF Abeta
      levels. In vitro analysis of the TF SNP showed a change in secreted Abeta
      consistent with the CSF phenotype and known Alzheimer's disease variants,
      demonstrating the utility of this approach in identifying SNPs that influence
      risk for disease via an Abeta-related mechanism.

PMID- 18813965
TI  - Spinal radiosurgery: technology and clinical outcomes.
AB  - The development of computer-based image guidance has allowed stereotactic
      radiosurgery and radiotherapy to be freed from the constraints imposed by the
      stereotactic frames once required for intracranial radiosurgery. This freedom has
      led to the application of radiosurgery to targets outside the brain. In this
      paper, we briefly review the technologies, treatment parameters, and clinical
      outcomes of radiosurgical treatment for spinal pathology, including metastatic
      tumors and rare but challenging lesions such as arteriovenous malformations and
      benign tumors. A special emphasis is put on the newest development, fiducial-less
      robotic radiosurgery. Spinal radiosurgery is associated with excellent rates of
      tumor control and pain relief with a good dose sparing of the highly sensitive
      spinal cord. Further research is required to optimize treatment strategies and to
      assess clinical benefits and toxicity in the long term.

PMID- 18813967
TI  - [Atopic exzema in adulthood].
AB  - The prevalence of atopic eczema (AE) in adulthood is 1-3%. A positive family
      history, early disease onset, a severe disease course in childhood, and
      comorbidity of other disorders among the circle of atopic forms are predictors
      for persistence of AE into adulthood; furthermore, genetic risk factors are
      assumed. Initial manifestation of AE in adulthood is also possible.
      Stress/psychological burden have been classified as the most important triggering
      factor of AE. To date a causal therapy for AE is not available. The basis of
      symptomatic treatment consists of stage-appropriate skin care and moisturizing
      local therapy, antiseptic agents for external application, and antipruritic
      agents. In cases of exacerbation topical corticosteroids and/or topical
      calcineurine inhibitors are used. For the adult patient with severe AE who cannot
      be treated effectively with the topical treatment options available, UV therapy
      and immunosuppressive or immunomodulatory systemic drugs are recommended.

PMID- 18813968
TI  - [Pain in the left hand especially pronounced in the ring finger and small
      finger].
AB  - A case is described of a female patient, who presented with permanent stabbing
      and burning pain in the ring finger and small finger of the left hand. Because of
      this pain neurolysis of the sulcus ulnaris had been carried out 4 months
      previously, which did not result in an improvement but led to a spreading of the
      symptoms to the whole hand. Diagnostic three-phase skeletal scintigraphy and
      neurography were performed. In 1999 breast cancer was diagnosed and surgically
      treated. Oncological follow-up 2 months before presentation revealed no
      conspicuous findings.Readers are encouraged to make their own diagnosis on the
      basis of the clinical findings and to discuss the case online
      (http://blogs.springer.com/DerSchmerz).

PMID- 18813971
TI  - Risk factors for lateral cervical lymph node involvement in follicular thyroid
      carcinoma.
AB  - BACKGROUND: Metastases from follicular thyroid carcinoma (FTC) are usually blood
      borne and far less to lymph nodes (LN). The present study was designed to
      evaluate the factors that are associated with LN metastases in patients operated
      on for FTC. METHODS: A retrospective review of 70 patients (25 men; mean age, 47
      (range, 14-92) years) operated on between January 1995 and December 2005 for FTC
      was undertaken. All patients had histopathology study of the regional LN and
      postoperative radioiodine scintigraphy. According to LN invasion, they were
      divided into two groups in which various parameters were compared. RESULTS: The
      length of follow-up was 52 (range 17-108) months. A total of 375 LN were examined
      from ipsilateral neck side and 87 LN from the contralateral side. LN metastases
      were found in five (7%) cases: all ipsilateral. Comparing data from the patients
      with and without LN metastases, respectively, age was 60 and 47 years (p = 0.12),
      male/female ratio was 1/4 and 24/41 (p = 0.44), tumor size was 68 and 37 mm (p <
      0.01), tumor differentiation (well/moderate) was 3/2 and 25/19 (p = 0.89),
      distant metastases were detected in 1 and 8 cases (p = 0.72) .The tumor size was
      >40 mm in 35 (50%) patients. All patients with LN metastases were found in this
      group (5/35; 14%). CONCLUSIONS: Follicular thyroid carcinoma results in
      metastases to regional lymph nodes in 7% of cases but only to the ipsilateral
      neck side. Tumor size is the only factor that impacts it. We do not recommend
      lymph node dissection in follicular thyroid carcinomas <4 cm.

PMID- 18813972
TI  - The role of staging laparoscopy for intraabdominal cancers: an evidence-based
      review.
AB  - Diagnostic laparoscopy is minimally invasive surgery for the diagnosis of
      intraabdominal diseases. The aim of this review is a critical examination of the
      available literature on the role of laparoscopy for the staging of intraabdominal
      cancers. A systematic literature search of English-language articles on MEDLINE,
      the Cochrane database of evidence-based reviews, and the Database of Abstracts of
      Reviews of Effects was performed for the period 1995-2006. The level of evidence
      in the identified articles was graded. The search identified and reviewed seven
      main categories that have received attention in the literature: esophageal
      cancer, gastric cancer, pancreatic cancer, hepatocellular carcinoma, biliary
      tract cancer, colorectal cancer, and lymphoma. The indications,
      contraindications, risks, benefits, diagnostic accuracy of the procedure, and its
      associated morbidity are discussed. The limitations of the available literature
      are highlighted, and evidence-based recommendations for the use of laparoscopy to
      stage intraabdominal cancers are provided.

PMID- 18813975
TI  - Technical skills assessment as part of the selection process for a fellowship in
      minimally invasive surgery.
AB  - INTRODUCTION: Selection of candidates for surgical fellowships has traditionally
      been based on subjective evaluations by the program directors and references from
      previous positions. The introduction of well-validated objective methods of
      assessment has allowed us to evaluate candidates' technical skills and base the
      selection process on objective, reliable, and transparent criteria. The aim of
      the study was to assess the applicability of such methods in current practice.
      MATERIALS AND METHODS: Prospective study. Eight surgeons, applying for a
      fellowship position in minimally invasive surgery (MIS), performed a previously
      validated assessment curriculum using a Virtual-Reality Laparoscopic Trainer
      (LapSim 3.0, Surgical Science, Gothenburgh, Sweden). Technical performance was
      evaluated using criteria registered by the simulator, i.e., time, error score,
      and efficiency of movements score. Candidates performed all the tasks in easy end
      medium level until reaching predefined criteria. If proficiency criteria were not
      achieved on easy or medium level after nine repetitions the test was considered
      as failed. Additionally, all applicants underwent an interview by two independent
      attending surgeons. Each applicant received a grade on a ten-point scale.
      RESULTS: Five out of the eight candidates failed the technical skills assessment
      test. One candidate failed to achieve proficiency criteria on easy level, one on
      medium, and three on difficult level. Evaluation scores, based on the interview
      of the candidates showed a good interrater reliability (Cronbach's alpha = 0.8).
      There was no significant correlation between the interviewers rating, and the
      applicants technical skills demonstrated during the test on the VR trainer
      (Spearman's rho = 0.182, p = 0.696). CONCLUSIONS: Evaluations by senior surgeons
      are reproducible and reliable. The introduction of technical skills assessment
      has the potential to improve the current method of candidate selection, making it
      more valid, objective, and transparent.

PMID- 18813976
TI  - Validation of a rodent model of Barrett's esophagus using quantitative gene
      expression profiling.
AB  - BACKGROUND: A rodent model of gastroduodenal-esophageal reflux can result in
      replacement of squamous esophageal mucosa with intestinal-type columnar mucosa
      and carcinoma. The validity of this model is debated, as it is unproven whether
      this mucosa is intestinal metaplasia due to reflux or represents migration of
      adjacent jejunal mucosa above the anastomosis. The aim of this study was to
      evaluate the esophageal intestinal-type mucosa in these animals by measuring
      expression of trefoil factor genes (TFF-1, -2, -3) and comparing it with adjacent
      jejunum in order to determine its etiology. METHODS: Twenty-five rats underwent
      esophagojejunostomy at the ligament of Treitz to induce reflux of gastric and
      duodenal contents. The animals were sacrificed at 16 weeks (n = 14) and 30 weeks
      (n = 11). After sacrifice, the distal esophagus, jejunum, and colon were
      obtained. RNA was isolated, reverse transcribed, and messenger RNA (mRNA)
      expression of TFF-1, -2, and -3 was measured with real-time polymerase chain
      reaction (PCR). Linear discriminant analysis classified samples based on gene
      expression. RESULTS: Esophageal intestinal-type mucosa was present at sacrifice
      in 18 animals. Compared to jejunum, the expression of TFF-1 and TFF-2 mRNA in the
      intestinal mucosa of the distal esophagus was increased (p = 0.0007 and p <
      0.0001, respectively). Expression of TFF-3 was also increased in esophageal
      intestinal mucosa compared with jejunum (p = 0.0002), but there was significant
      overlap in expression between these tissues for this gene. Linear discriminant
      analysis misclassified esophageal intestinal-type mucosa as jejunum in only one
      case. In no cases was jejunum misclassified as esophageal intestinal-type mucosa.
      CONCLUSION: The gene expression profile of esophageal intestinal-type mucosa
      following surgically induced reflux in a rodent model indicates that this
      represents intestinal metaplasia, not proximal migration of jejunum. This
      validates this model for studying the pathogenesis of Barrett's esophagus. Use of
      this model has potential for assessment of the impact of various therapies on the
      natural history of reflux disease.

PMID- 18813977
TI  - Expert benchmark for the GI Mentor II.
AB  - BACKGROUND: There is increasing interest in the use of virtual-reality simulators
      in general surgery residency training. Many simulators lack a benchmark against
      which trainees can measure competence and skill. METHODS: Surgeons who had
      performed over 1,000 colonoscopies were evaluated on module 1, case 5 of the GI
      Mentor I or II virtual-reality endoscopy simulator (Simbionix, Cleveland).
      Participants were given 5 min to familiarize themselves with the simulator, and
      then performed the study case with standardized instructions. Metrics were
      recorded by using the previously calibrated simulator. RESULTS: Twenty-three
      surgeons (21 male, 2 female) participated. Mean height was 69.6 +/- 2.6 inches,
      mean age 51 +/- 9 years, median surgical glove size 7.5, and surgeons had 18.8 +/
      10.1 years of practice, and did 8 +/- 6 colonoscopies weekly. Ten participants
      had advanced training in endoscopy, laparoscopy or colorectal surgery; eight had
      used the simulator before, of whom six had used it once. Mean time to complete
      the study case was 13.6 +/- 5.3 min and time to reach the cecum was 6.5 +/- 4.3
      min. Participants examined 92.3 +/- 3.6% of the simulated colonic mucosa with a
      clear view of the lumen 89.5 +/- 4.2% of the time. Total time the colon was
      looped was 22 +/- 35 s (range 0-133 s). The overall efficiency of screening was
      70.33 +/- 23.45% (range 20-94%). Participants tended to mistake normal simulated
      colonic structures as pathology. CONCLUSION: Performance on a virtual-reality
      endoscopic simulator has a wide amount of variability even among a group of
      experienced endoscopists. Expert benchmark tests should be performed on
      simulators that will be used for resident assessment prior to any attempts at
      certification of competence.

PMID- 18813978
TI  - Esophageal manometric characteristics and outcomes for laparoscopic esophageal
      diverticulectomy, myotomy, and partial fundoplication for epiphrenic diverticula.
AB  - PURPOSE: The purpose of this study is to characterize the esophageal motor and
      lower esophageal sphincter (LES) abnormalities associated with epiphrenic
      esophageal diverticula and analyze outcomes for laparoscopic esophageal
      diverticulectomy, myotomy, and partial fundoplication. METHODS: The endoscopic,
      radiographic, manometric, and perioperative records for patients undergoing
      laparoscopic esophageal diverticulectomy, anterior esophageal myotomy, and
      partial fundoplication from 8/99 until 9/06 were reviewed from an Institutional
      Review Board (IRB)-approved outcomes database. Data are given as mean +/-
      standard deviation (SD). RESULTS: An esophageal body motor disorder and/or LES
      abnormalities were present in 11 patients with epiphrenic diverticula; three
      patients were characterized as achalasia, one had vigorous achalasia, two had
      diffuse esophageal spasm, and five had a nonspecific motor disorder. Presenting
      symptoms included dysphagia (13/13), regurgitation (7/13), and chest pain (4/13).
      Three patients had previous Botox injections and three patients had esophageal
      dilatations. Laparoscopic epiphrenic diverticulectomy with an anterior esophageal
      myotomy was completed in 13 patients (M:F; 3:10) with a mean age of 67.6 +/- 4.2
      years, body mass index (BMI) of 28.1 +/- 1.9 kg/m2 and American Society of
      Anesthesiologists (ASA) 2.2 +/- 0.1. Partial fundoplication was performed in
      12/13 patients (Dor, n = 2; Toupet, n = 10). Four patients had a type I and one
      patient had a type III hiatal hernia requiring repair. Mean operative time was
      210 +/- 15.1 min and mean length of stay (LOS) was 2.8 +/- 0.4 days. Two grade II
      or higher complications occurred, including one patient who was readmitted on
      postoperative day 4 with a leak requiring a thoracotomy. After a mean follow-up
      of 13.6 +/- 3.0 months (range 3-36 months), two patients complained of mild solid
      food dysphagia and one patient required proton pump inhibitor (PPI) for
      gastroesophageal reflux disease (GERD) symptoms. CONCLUSION: The majority of
      patients with epiphrenic esophageal diverticula have esophageal body motor
      disorders and/or LES abnormalities. Laparoscopic esophageal diverticulectomy and
      anterior esophageal myotomy with partial fundoplication is an appropriate
      alternative with acceptable short-term outcomes in symptomatic patients.

PMID- 18813979
TI  - Immunologic parameters during NOTES compared with laparoscopy in a randomized
      blinded porcine trial.
AB  - BACKGROUND: It remains unclear if the natural orifice translumenal endoscopic
      surgery (NOTES) technique is less invasive than laparoscopy. Serum interleukins
      and peritoneal cellular response have been utilized to support the immunologic
      difference between open and laparoscopic surgery. We hypothesized that there
      would be no difference between cytokine levels during NOTES or laparoscopic
      peritoneoscopy. METHODS: Twelve pigs were assigned to NOTES or standard
      laparoscopy with permuted block randomization. Each group underwent 90 min of
      diagnostic peritoneoscopy using CO(2) for laparoscopy and air for NOTES
      pneumoperitoneum. Blood draws were obtained at baseline, at procedure end, and on
      postoperative days (POD) 1, 2, and 7. Quantification of cytokines (IL-1b and TNF
      alpha) was performed with a Duo Set Porcine enzyme-linked immunosorbent assay
      (ELISA). Laboratory results were captured by a technician blinded to the research
      question, and data analysis was performed by an investigator blinded to the
      procedure using t-test and repeated measures linear model. The study was approved
      by the institutional animal care and use committee (IACUC). RESULTS: All
      procedures were successfully completed. One NOTES animal succumbed to hemorrhagic
      gastritis (day 3). All other animals thrived to POD 14, with no gross infections
      at necropsy. Animals undergoing laparoscopy had lower mean arterial pH than NOTES
      animals (p < 0.001). Serum and intraperitoneal white blood cell (WBC) counts were
      similar between the groups. Mean interleukin-1b levels at baseline, at the end of
      the procedure and at 48 h did not differ (0.50 and 0.31; p = 0.65). TNF-alpha
      levels did not differ at baseline or procedure end but increased in the NOTES
      group on POD 1, persisting to POD 7. Tumor necrosis factor-alpha (TNF-alpha)
      decreased in the laparoscopy group (p = 0.005). CONCLUSION: Cytokines and WBC did
      not differ between laparoscopic and NOTES groups during the initial 24 h. These
      findings do not currently support the assumption that NOTES is less invasive than
      laparoscopy. The late TNF-alpha elevation contradicts other studies and requires
      further examination.

PMID- 18813980
TI  - Comparison of laparoscopic truncal vagotomy with gastrojejunostomy and open
      surgery in peptic pyloric stenosis.
AB  - BACKGROUND: Little is known about the advantages of laparoscopic truncal vagotomy
      with gastrojejunostomy (LTVGJ) over open truncal vagotomy with gastrojejunostomy
      (OTVGJ) for peptic pyloric stenosis (PPS). This study aimed to highlight the role
      of minimally invasive surgery in the form of LTVGJ for PPS. METHODS: From March
      1999 to October 2005, 21 patients with PPS underwent LTVGJ (n = 13) and OTVGJ (n
      = 8). We analyzed intraoperative and postoperative outcomes retrospectively.
      RESULTS: Two groups had similar demographic characteristics. Significantly
      shorter operating time, hospital stay, time to presence of bowel sounds, and time
      to tolerate a diet were the advantages of LTVGJ, while blood loss was higher in
      OTVGJ. There were significant differences in weight gain between the two groups
      after surgery during follow-up. CONCLUSIONS: This study suggests that LTVGJ is a
      feasible technique, and intermediate follow-up reveals good symptomatic results
      when used for PPS.

PMID- 18813981
TI  - Laparoscopic ventral hernia repair: innovative anatomical closure, mesh insertion
      without 10-mm transmyofascial port, and atraumatic mesh fixation: a preliminary
      experience of a new technique.
AB  - BACKGROUND: Generous overlap by a well-transfixed mesh is important in
      laparoscopic ventral hernia repair (LVHR). Mesh is usually introduced through a
      10-mm trocar and fixed by tackers or transfixed by sutures. Ten-millimeter trocar
      sites are more prone to hernia development. Transfixation done using a suture
      passer inflicts some trauma and the site may become painful. This study reports a
      mesh insertion technique avoiding a 10-mm myofascial port, double-breasted
      fascial closure of the hernial defect, and transfixation in a relatively
      atraumatic manner. METHODS: This prospective study was conducted by enrolling the
      patients attending our surgery clinic. They were candidates for LVHR. Informed
      consent was obtained from each patient before the procedure. The study was
      approved by the Ethical Review Board of the Hospital and conducted as per good
      clinical practice (GCP) guidelines. RESULTS: Between April 2004 and June 2006, 29
      ventral hernia patients were enrolled without any exclusion. All patients had
      LVHR performed with this technique. Mean operative time and hospital stay were 65
      min and <1 day, respectively. There were no perioperative complications,
      conversion, infection, trocar site or recurrent herniation or mortality. The
      majority of the patients were operated on as day-care surgery. Patients were
      followed up telephonically for the first 48 h and then by visiting us regularly.
      There was no postoperative visible bulge. CONCLUSION: Mesh insertion by avoiding
      10-mm trocar, double-breasted defect closure, and transfixation using atraumatic
      needles is a technically easy, safe, and patient-friendly procedure.

PMID- 18813982
TI  - Is right laparoscopic donor nephrectomy right?
AB  - INTRODUCTION: Laparoscopic donor nephrectomy has become the standard of care in
      many renal transplant centers. Many centers are reluctant to perform right
      laparoscopic donor nephrectomies, primarily due to concerns about transplanting a
      kidney with a short renal vein. METHODS: A retrospective review of 26 right and
      24 left consecutive donor nephrectomies and their recipients was performed.
      Patient demographics, preoperative, perioperative, and postoperative data were
      recorded and compared. RESULTS: Patient demographics were similar between groups.
      Multiple vessels were encountered more frequently on the right side (10 vs. 3, p
      = 0.04) and the donated kidney had lesser preoperative function in the right
      group as determined by nuclear medicine imaging (46.5% vs. 49.4%, p < 0.001).
      Donor operating times were less in the right group (198 vs. 226 min, p = 0.016).
      There was no difference in implantation difficulty as demonstrated by similar
      operative and warm ischemia times. Complication rates were similar between both
      groups of donors and recipients. CONCLUSIONS: Right laparoscopic donor
      nephrectomy requires less operating time than, and is associated with similar
      outcomes for donors and recipients as, left laparoscopic donor nephrectomy. Right
      laparoscopic donor nephrectomy may be preferable in general and should be
      considered when multiple renal vessels are present on the left side and/or when
      preoperative function of the left kidney is greater than the right.

PMID- 18813983
TI  - Preoperative predictability of the short esophagus: endoscopic criteria.
AB  - BACKGROUND: Short esophagus is a common cause of failure of antireflux surgery.
      Minimally invasive intervention for short esophagus is technically difficult.
      Reliable predictors of short esophagus would allow appropriate referral and
      better outcomes. The aim of this study is to investigate the preoperative
      predictability of the short esophagus in patients undergoing antireflux surgery.
      METHODS: Eighty-five patients with Collis gastroplasty and antireflux surgery
      (1994-2007) at a single institution form group A. Control group (B) comprises 205
      consecutive patients undergoing primary antireflux surgery (2004-2007).
      Retrospective review of prospectively collected data was completed. Esophageal
      length index (ELI) was calculated as the ratio of endoscopic esophageal length
      (in cm) to height (in meters). RESULTS: Patients requiring Collis gastroplasty
      (group A) tend to be older while there were no significant differences in sex,
      height, weight, and body mass index distribution between groups. Mean endoscopic
      esophageal length (EEL) as measured from incisor to esophagogastric junction was
      significantly shorter in group A (32.4 cm) as compared with group B (36.2c m) (p
      < 0.0001). Esophageal length index (ELI) of less than 19.5 had 83% negative
      predictive value with 95% specificity. CONCLUSIONS: Patients with an ELI of less
      than 19.5 or with stricture have higher risk for having a short esophagus.

PMID- 18813984
TI  - In situ measurement and modeling of biomechanical response of human cadaveric
      soft tissues for physics-based surgical simulation.
AB  - BACKGROUND: Development of a laparoscopic surgery simulator that delivers high
      fidelity visual and haptic (force) feedback, based on the physical models of soft
      tissues, requires the use of empirical data on the mechanical behavior of intra
      abdominal organs under the action of external forces. As experiments on live
      human patients present significant risks, the use of cadavers presents an
      alternative. We present techniques of measuring and modeling the mechanical
      response of human cadaveric tissue for the purpose of developing a realistic
      model. The major contribution of this paper is the development of physics-based
      models of soft tissues that range from linear elastic models to nonlinear
      viscoelastic models which are efficient for application within the framework of a
      real-time surgery simulator. METHODS: To investigate the in situ mechanical,
      static, and dynamic properties of intra-abdominal organs, we have developed a
      high-precision instrument by retrofitting a robotic device from Sensable
      Technologies (position resolution of 0.03 mm) with a six-axis Nano 17 force
      torque sensor from ATI Industrial Automation (force resolution of 1/1,280 N along
      each axis), and used it to apply precise displacement stimuli and record the
      force response of liver and stomach of ten fresh human cadavers. RESULTS: The
      mean elastic modulus of liver and stomach is estimated as 5.9359 kPa and 1.9119
      kPa, respectively over the range of indentation depths tested. We have also
      obtained the parameters of a quasilinear viscoelastic (QLV) model to represent
      the nonlinear viscoelastic behavior of the cadaver stomach and liver over a range
      of indentation depths and speeds. The models are found to have an excellent
      goodness of fit (with R (2) > 0.99). CONCLUSIONS: The data and models presented
      in this paper together with additional ones based on the principles presented in
      this paper would result in realistic physics-based surgical simulators.

PMID- 18813985
TI  - Role of three-dimensional anorectal ultrasonography in the assessment of rectal
      cancer after neoadjuvant radiochemotherapy: preliminary results.
AB  - BACKGROUND: Three-dimensional anorectal ultrasound (3-DAUS) scanning provides
      accurate information on tumor size and its relation to the anal muscles. The
      purpose of this study was to evaluate the ability of 3-DAUS to assess response to
      radiochemotherapy (RCT) for rectal cancer by comparing 3-DAUS images to
      pathological findings. METHODS: Twenty-five patients (mean age 52.4 years),
      staged as T2 (n = 3), T3 (n = 16) or T4 (n = 6), with lymph node metastases in 12
      cases, were submitted to neoadjuvant RCT, followed by a second 3-DAUS scan 7
      weeks later. The patients were grouped according to the distance (cm) between the
      distal tumor edge and the proximal border of the internal anal sphincter (IAS)
      (group I, presenting anal canal invasion; group II, < or =2.0 cm; group III, >2.0
      cm). All patients were operated on and the pathological findings were compared to
      post-RCT 3-DAUS scanning results. RESULTS: Four (16%) patients (three in group I,
      one in group II) experienced complete tumor regression. Fourteen (56%) tumors
      (six in group I, seven in group II, and one in group III) regressed partially.
      Distance to the IAS was >2.0 cm in eight patients (seven in group II and one in
      group III). The remaining six (24%) patients (all group I) experienced no
      regression. 3-DAUS and pathological findings were concordant in 24 (96%)
      patients, with only one (4%) nonconclusive post-RCT 3-DAUS result found to be a
      residual tumor. Tumor regression made sphincter-saving surgery possible in 13
      patients (eight in group III, four complete tumor regression, and one
      nonconclusive on 3-DAUS). Pathological examination revealed free distal margins
      in all cases. The index of agreement between lymph node metastases on post-RCT 3
      DAUS and surgical specimens was moderate (84%). CONCLUSION: 3-DAUS can aid
      significantly in the choice of surgical approach following RCT. However, a
      greater sample of patients is required to establish sufficiently accurate post
      RCT 3-DAUS parameters.

PMID- 18813986
TI  - Recurrences after laparoscopic repair of ventral and incisional hernia: lessons
      learned from 505 repairs.
AB  - BACKGROUND: All hernia recurrences in a series of 505 patients who underwent
      laparoscopic repair of a ventral hernia (n=291) or incisional hernia (n=214) were
      analyzed to identify factors responsible for the recurrence. METHODS: In all
      laparoscopic repairs, an expanded polytetrafluoroethylene prosthesis overlapping
      the hernia margins by >or=3 cm was fixed with a double ring of tacks alone
      (n=206) or with tacks as well as sutures (n=299). During the mean follow-up time
      of 31.3 +/- 18.4 months, nine patients (1.8%) had a recurrence, eight of which
      were repaired laparoscopically. Operative reports and videotapes of all initial
      repairs and repairs of recurrences were analyzed. RESULTS: All recurrences
      followed an incisional hernia repair (p<0.001). Five recurrences developed after
      mesh fixation with both tacks and sutures and four after mesh fixation with tacks
      alone (p=1.0). All recurrences were at the site of the apparently sufficient
      original incision scar: in eight patients, the recurrent hernia was attached to
      the mesh; in one, it developed in another part of the scar. All initial repairs
      had been performed without technical errors. Upon repair of the recurrences, a
      new, larger mesh was placed over the entire incision, not just the hernia. There
      were no re-recurrences during follow-up (mean 19.8+/-10.3 months). CONCLUSIONS:
      Recurrence after incisional hernia repair appears to be due primarily to
      disregard for the principle that the whole incision--not just the hernia--must be
      repaired. Our experience supports the idea that the entire incision has a
      potential for hernia development. Insufficient coverage of the incision scar is a
      risk factor for recurrence after laparoscopic repair of ventral and incisional
      hernia.

PMID- 18813987
TI  - What is going on in augmented reality simulation in laparoscopic surgery?
AB  - BACKGROUND: To prevent unnecessary errors and adverse results of laparoscopic
      surgery, proper training is of paramount importance. A safe way to train surgeons
      for laparoscopic skills is simulation. For this purpose traditional box trainers
      are often used, however they lack objective assessment of performance. Virtual
      reality laparoscopic simulators assess performance, but lack realistic haptic
      feedback. Augmented reality (AR) combines a virtual reality (VR) setting with
      real physical materials, instruments, and feedback. This article presents the
      current developments in augmented reality laparoscopic simulation. METHODS:
      Pubmed searches were performed to identify articles regarding surgical simulation
      and augmented reality. Identified companies manufacturing an AR laparoscopic
      simulator received the same questionnaire referring to the features of the
      simulator. RESULTS: Seven simulators that fitted the definition of augmented
      reality were identified during the literature search. Five of the approached
      manufacturers returned a completed questionnaire, of which one simulator appeared
      to be VR and was therefore not applicable for this review. CONCLUSION: Several
      augmented reality simulators have been developed over the past few years and they
      are improving rapidly. We recommend the development of AR laparoscopic simulators
      for component tasks of procedural training. AR simulators should be implemented
      in current laparoscopic training curricula, in particular for laparoscopic
      suturing training.

PMID- 18813988
TI  - Learning curve of laparoscopic surgery for gastric cancer, a laparoscopic distal
      gastrectomy-based analysis.
AB  - BACKGROUND: The application of laparoscopic gastrectomy in management of gastric
      cancer is being propagated rapidly. Training and education play important role
      during this process. The purpose of this study is to define the learning curve of
      laparoscopic gastrectomy to obtain an insight into this training process.
      METHODS: All 362 cases of laparoscopic gastrectomy from January 1998 to July 2007
      were enrolled and divided into 12 groups of 30 cases each in time sequence. The
      learning curve was defined with the split group method. Laparoscopic distal
      gastrectomy was extracted from the 12 groups and the means of operation time and
      intraoperative blood loss were compared to define the learning curve. Then
      general data and variables including occurrence of systematic inflammatory
      response syndrome (SIRS), complications, and conversion to open surgery were
      compared among the phases of learning curve. RESULTS: A three-phase learning
      curve of laparoscopic gastrectomy was defined from the laparoscopic distal
      gastrectomy-based analysis, which included a training phase for the first 120
      cases of operation, an intermediate phase for the following 90 cases, and a well
      developed phase for the last 152 cases. Learning was considered to be complete
      after 60-90 operations in the training phase. For most variables, the differences
      among three phases were statistically significant except for the rate of
      complications. CONCLUSIONS: There was a significant learning curve, composed of
      three phases. Experience of about 60-90 cases of operation was required for
      completion of learning.

PMID- 18813989
TI  - Socioeconomic predictors of weight loss after laparoscopic Roux-Y gastric bypass.
AB  - INTRODUCTION: Successful weight loss after laparoscopic Roux-Y gastric bypass
      (LRYGB) hinges on many elements including neurohormonal, anatomical, and
      postoperative behavioral changes. To date, the effects of socioeconomic factors
      have been inadequately studied. We examine several components of socioeconomic
      status and its relationship to weight loss after LRYGB. METHODS: Between August
      2002 and July 2006, 405 LRYGB were performed by a single surgeon. Patient
      demographics were entered into a longitudinal, prospective database. At 1-year
      follow-up, 309 patients were available for analysis. Regional median household
      income (RMAHI) and primary insurance carrier were used as surrogates for
      preoperative socioeconomic status. Analysis of covariance (ANCOVA) test was used
      for statistical analysis. According to RMAHI, we divided the patients into three
      groups: US $20,001-40,000 (group A, n = 67), US $40,001-60,000 (group B, n =
      153), and more than US $60,000 (group C, n = 89). Initial body mass index (BMI)
      was 52.76 +/- 1.01, 51.28 +/- 0.67, and 48.87 +/- 0.94 kg/m2, respectively.
      Additionally, patients were divided according to private insurance or state-based
      insurance. A total of 274 patients had private insurance, with an initial mean
      BMI of 50.6 kg/m2, and 35 patients had state-based insurance, with an initial BMI
      of 53.0 kg/m2. RESULTS: After 1 year, weight loss in groups A, B and C was 110.6
      +/- 4.3, 110.0 +/- 2.5, and 103.9 +/- 3.6 lb with BMI decrease of 17.7 +/- 0.6,
      17.7 +/- 0.4, and 16.9 +/- 0.6 kg/m2, respectively. Weight loss in the private
      insurance group was 49.2 +/- 0.9 kg compared with 50.2 +/- 2.3 kg in the state
      based group with BMI decrease of 17.4 +/- 0.3 and 18.4 +/- 0.8 kg/m2,
      respectively. There were no statistical significances in the effect of
      socioeconomic status, median household income, and insurance carrier on
      postoperative weight loss. CONCLUSION: With appropriate patient selection, the
      socioeconomic status of patients undergoing LRYGB does not affect postoperative
      weight loss.

PMID- 18813990
TI  - Laparoscopic total extraperitoneal inguinal hernia repair with nonfixation of the
      mesh for 1,692 hernias.
AB  - BACKGROUND: This study aimed to examine the recurrence rate and postoperative
      pain in total extraperitoneal repair (TEP) performed without fixation of the mesh
      and to compare the rates with those for repairs using fixation of mesh. METHODS:
      A retrospective analysis was conducted over a 3-year period for 929 patients
      (1,753 hernias) who had undergone TEP. The recurrence rate, pain scores at 24 h
      and 1 week, hospital stay, days until resumption of normal activities, seroma
      formation, and urinary retention rates were noted. RESULTS: Of the 929 patients
      (1,753 hernias), the mesh was fixed (Fx) for 33 (61 hernias) and not fixed (NFx)
      for 896 (1,692 hernias). The follow-up period ranged from 6 to 40 months (mean,
      17 months). The two groups did not differ significantly in terms of mean
      operating time, proportion of patients who had minimal or no pain (score, 1 or 2)
      24 h after surgery, or proportion of patients who were totally pain free (score =
      1) 1 week postoperatively. The proportions of patients reporting pain at the end
      of 1 month, the incidence of seroma formation and urinary retention, the hospital
      stay, and the days until resumption of normal activities were significantly
      greater in the Fx group than in the NFx group (p < 0.0001). Two patients (0.22%)
      in the NFx group had recurrence and one patient in the Fx group underwent
      conversion to open hernia repair. CONCLUSIONS: This study found TEP without mesh
      fixation to be safe and feasible with no increase in recurrence rates. The TEP
      procedure is associated with significantly less pain at 4 weeks, lower incidence
      of urinary retention and seroma formation, shorter hospital stay, and early
      resumption of normal activities.

PMID- 18813991
TI  - Colorectal resection, both open and laparoscopic-assisted, in patients with
      benign indications is associated with proangiogenic changes in plasma
      angiopoietin 1 and 2 levels.
AB  - INTRODUCTION: Plasma vascular endothelial growth factor (VEGF) levels are
      increased after surgery and may stimulate tumor growth after cancer resection.
      Angiopoietin 1 (Ang 1) and Ang 2 are proteins that impact VEGF-related
      angiogenesis (VRA). Ang 1 stabilizes mature vessels and inhibits VRA, whereas Ang
      2 destabilizes vessels and promotes VRA. The ratio of Ang 1 to Ang 2 reflects the
      net effect; a low ratio promotes VRA. This study's purpose was to determine the
      impact of open and minimally invasive (MIS) colorectal resection (CR) for benign
      indications on plasma Ang 1 and 2 levels. METHODS: A total of 30 patients
      operated by MIS and 26 operated by open procedure were studied. Plasma was
      obtained preoperatively (PO) and on postoperative days (POD) 1 and 3. Plasma Ang
      1 and Ang 2 levels were assessed via enzyme-linked immunosorbent assay (ELISA) in
      duplicate. Data were compared using Wilcoxon's matched-pair test and the Mann
      Whitney U-test (significance p < 0.05). RESULTS: Indications, types of resection,
      and morbidity for the groups were similar. The mean MIS incision length was 4.7
      +/- 1.6 cm while it was 16.8 +/- 7.1 cm for the open group (p = 0.0001). For both
      groups Ang 2 levels were significantly higher and the Ang 1 to Ang 2 ratio was
      significantly lower on POD 1 and 3 compared with preoperative results. Ang 1
      levels were significantly decreased on POD 1 and 3 in the MIS group but only on
      POD 1 in the open group. For unclear reasons, preoperative Ang 1 levels and Ang 1
      to Ang 2 ratios were significantly different between the groups, which precludes
      comparison of the postoperative results between groups. CONCLUSION: CR for benign
      pathology results in higher Ang 2 levels, lower Ang 1 levels, and lower Ang 1 to
      Ang 2 ratios early after surgery. These alterations are proangiogenic. These
      results, plus the already noted VEGF increases, suggest that surgery results in
      proangiogenic plasma protein changes that may stimulate tumor growth early after
      surgery. The duration of the Ang 1 and 2 changes needs to be determined.

PMID- 18813992
TI  - Assessment of low prostate weight as a determinant of a higher positive margin
      rate after laparoscopic radical prostatectomy: a prospective pathologic study of
      1,500 cases.
AB  - BACKGROUND: The assessment of prostate weight as a determinant of a high prostate
      margin rate after laparoscopic radical prostatectomy has not been studied.
      METHODS: Prospective pathologic findings of 1,500 patients who underwent
      laparoscopic radical prostatectomy (LRP, 399 cases) and da Vinci prostatectomy
      (DVP, 1,101 cases) between December 2000 to June 2006 at City of Hope National
      Medical Center were evaluated. Gleason score, pathologic stage, the presence or
      absence of positive margins, extraprostatic tumor extension, and seminal vesicle
      involvement by tumor were recorded in all patients. Preoperational serum prostate
      specific antigen (PSA) levels were recorded in all but 13 cases. These parameters
      were then correlated with prostate weight. RESULTS: Of 1,500 patients, 345 had
      one or more positive margins (23%). Patients with low median prostate weight (49
      g) had a significantly higher positive margin rate (p < 0.0001) and incidence of
      extraprostatic extension by tumor (p = 0.04), and were 1.523 times more likely to
      have positive margins [95% confidence interval (CI) 1.167-1.985]. CONCLUSION: We
      conclude that low prostate weight may be a determinant of a higher recurrence
      rate and more aggressive disease.

PMID- 18813993
TI  - Accuracy of endoanal ultrasound in the follow-up assessment for squamous cell
      carcinoma of the anal canal treated with radiochemotherapy.
AB  - BACKGROUND: Radiochemotherapy has largely replaced surgery in the treatment for
      squamous cell cancer of the anal canal. Transanal ultrasonography is well
      documented as an important investigation method in the management of anal
      carcinoma. This study aimed to evaluate the accuracy of endoanal ultrasound in
      the study of the postradiation findings and to distinguish between postradiation
      fibrosis, residual tumor, and local recurrence. METHODS: The study enrolled 16
      consecutive patients with biopsy-proven squamous carcinoma of the anal canal
      between 2003 and 2006. All the patients underwent a pretreatment and at least
      four posttreatment endosonographies, according to the follow-up period. All the
      patients were treated with the same radiochemotherapy protocol. RESULTS: Nine
      patients had stage uT2 disease; none had uT3 disease; and seven had uT4 disease.
      There was no evidence of residual tumor in the T2 group after treatment. In the
      T4 patients after treatment, ultrasound demonstrated tumor regression or
      abnormalities considered to be radiation-induced changes rather than residual
      diseases. Only for three patients was a posttreatment biopsy performed to
      evaluate recurrence (two uT2 and one uT4). Surgical treatment of recurrence was
      performed for two uT4 patients. CONCLUSIONS: Endoanal ultrasound is a safe and
      effective method for evaluating and following anal cancer before and after
      treatment. Experience and evaluation during the period of the ultrasonographic
      abnormalities could give a clear idea concerning the evolution of the anal tumors
      treated with radiochemotherapy.

PMID- 18813994
TI  - Robot-assisted laparoscopic total and partial gastric resection with D2 lymph
      node dissection for adenocarcinoma.
AB  - BACKGROUND: Lymph node dissection and esophageal anastomosis, considered the more
      demanding steps of laparoscopic gastrectomy for gastric adenocarcinoma, can be
      performed with the use of a remote-controlled robot. METHODS: Thirteen patients
      with a histologically proved gastric cancer (six stage I, six stage II, and one
      stage III) were enrolled in a prospective study to assess feasibility and safety
      of the Da Vinci surgical system in total and partial gastrectomy with extended
      lymph node dissection. Outcome measures were conversion rate, intra- and
      postoperative morbidity and mortality, operative time, blood loss, number of
      lymph nodes harvested, and macroscopic and microscopic evaluation of resection
      margins. RESULTS: Eight distal, four total, and one proximal laparoscopic
      gastrectomies were completed without conversion. Extended lymph node dissection,
      and esophagojejunal and esophagogastric anastomoses were successfully carried out
      using the da Vinci System. Mean operative time was 286 +/- 32.6 min and blood
      loss was 103 +/- 87.5 ml. Mean number of nodes retrieved was 28.1 +/- 8.3 and all
      resection margins were negative. There was no mortality. Trocar bleeding
      requiring laparoscopy was the only major complication encountered. No recurrence
      occurred during a mean follow-up time of 12.2 +/- 4.5 months. CONCLUSIONS: Robot
      assisted laparoscopic lymph node dissection and esophageal anastomosis are
      feasible and safe. Longer follow-up time and randomized studies are needed to
      evaluate long-term outcome and clinical advantages of this new technology.

PMID- 18813995
TI  - Multimedia article. Prone thoracoscopic thoracic duct ligation for postsurgical
      chylothorax.
AB  - BACKGROUND: Chylothorax after complex abdominal and thoracic procedures remains a
      challenging complication with a mortality rate reaching 50% if untreated.
      Iatrogenic trauma accounts for almost 20% of all chyle leaks, and esophagectomy
      is the most common iatrogenic cause. Consequences of ongoing chyle leak include
      dehydration, malnutrition, and immunocompromise. METHODS: When nonoperative
      management techniques fail, prompt ligation of the thoracic duct at the
      diaphragmatic hiatus should be attempted. The authors present prone thoracoscopic
      thoracic duct ligation performed for two patients after laparoscopic
      transthoracic esophagectomy and revision paraesophageal hernia repair. RESULTS:
      The prone position for thoracoscopic thoracic duct ligation offers several
      benefits to the surgeon. Gravity retracts the lung anteriorly, exposing the
      diaphragmatic hiatus. Single-lumen endotracheal intubation combined with low
      pressure carbon dioxide insufflation efficiently collapses the lung to create
      ample working space. For the two reported patients, only three trocars were
      necessary to complete suture ligation of the thoracic duct via the right chest.
      Both patients had complete resolution of their chylothorax and recovered
      uneventfully. Based on this experience, the authors currently advocate early
      thoracoscopic treatment for cost and morbidity savings. CONCLUSIONS: The authors
      believe prone thoracoscopic thoracic duct ligation offers significant advantages
      to the patient in preventing the dangerous consequences of chyle leak in a
      timely, minimally invasive fashion. Importantly, the prone technique with carbon
      dioxide insufflation makes the technical challenges of thoracic duct ligation
      more facile for the surgeon.

PMID- 18813996
TI  - Transvaginal laparoscopic cholecystectomy: endoscopically assisted.

PMID- 18813997
TI  - Gastric lymphatic mapping for sentinel node biopsy by natural orifice
      transluminal endoscopic surgery (NOTES).
AB  - BACKGROUND: Sentinel node biopsy is proposed as sufficiently reliable in
      determining the lymph node status of early gastric cancer to justify curtailed
      resection margins if negative. Its performance by natural orifice transluminal
      endoscopic surgery (NOTES) could therefore expand the patient cohort able to
      undergo solely endoscopic resection of their primary. METHODS: A transvaginal
      NOTES technique was utilized in six pigs (mean weight 30 kg). The posterior
      colpotomy and pneumoperitoneum was created by a standard double-channel flexible
      videoendoscope which was then used to perform peritoneoscopy. Concomitant
      gastroscopy allowed selection of a site along the greater curvature for lymphatic
      mapping by submucosal injection of methylene blue (3 ml). Furthermore, torque
      upon this endoscope allowed the posterior surface of the stomach and retrogastric
      space to become accessible to the transvaginal endoscope. In surveying the
      mapping in vivo, the intraperitoneal scope could follow blue-stained efferent
      lymphatic channels to their first-order draining nodes (i.e., sentinel nodes).
      Conventional instruments worked down the scope's channels were then used to
      perform the excisional biopsy. At procedure end, the animals underwent immediate
      laparotomy to ensure the safety and adequacy of the procedure. RESULTS: Each
      procedure was technically successful. Colpotomy, pneumoperitoneum, and
      peritoneoscopy were promptly achieved (mean 8 min). Post injection, blue efferent
      lymphatic channels were immediately appreciable in every animal. Five animals had
      sentinel nodes in their retropyloric region while the last mapped cephalad
      towards the esophagogastric junction. Two animals had alternative drainage
      channels identifying additional sentinel nodes. All blue nodes were dissected
      cleanly by the intraperitoneal scope and retrieved intact per vaginam. Mean
      lymphadenectomy time was 19 min. At laparotomy, there was no hematoma, ongoing
      hemorrhage, or visceral injury in any pig. There were no residual, missed stained
      nodes or channels. CONCLUSION: NOTES sentinel node biopsy for the stomach is
      technically accomplishable in this experimental model. This proof of concept
      should encourage serious consideration of its applicability to clinical practice.

PMID- 18813998
TI  - Tumor ablation therapy of liver cancers with an open magnetic resonance imaging
      based navigation system.
AB  - BACKGROUND: As minimally invasive treatments for liver cancers, percutaneous
      ablation therapies represent a valid alternative to liver resections, especially
      in patients with poor liver function. Recently, image-guided surgical and
      interventional procedures using open magnetic resonance imaging (MRI) have been
      introduced. METHODS: We performed percutaneous ablation therapy for 51 nodules of
      liver cancer in 34 patients using a navigation system based on open MRI. During
      the ablation therapy, the ultrasonography (US) probe, needle, and tumor were
      displayed on the MR image. Immediately after the procedure, the therapeutic
      effect was evaluated by open MRI. RESULTS: In all cases, percutaneous puncture
      into the tumors was successful, even in the case of tumor undetectable by US.
      Mean fiducial registration error was approximately 3 mm. MR images captured after
      the procedure clearly demonstrated the ablated area. No mortality or major
      complications occurred, except for mild hemorrhage, pyrexia, and ascites.
      CONCLUSIONS: We developed a novel navigation system integrating US and MR images
      using open MRI for percutaneous ablation therapy of liver cancers. The presented
      system allows a safe and accurate approach to liver cancers, especially certain
      tumors that cannot be adequately visualized by US, and an evaluation of
      therapeutic results immediately after the procedures.

PMID- 18813999
TI  - Transvaginal endoscopic partial gastrectomy in porcine models: the role of an
      extra endoscope for gastric control.
AB  - BACKGROUND: Transvaginal natural orifice translumenal endoscopic surgery (NOTES)
      gastrectomy is technically challenging, because wide perigastric dissection under
      appropriate tissue triangulation is unfeasible with current endoscopic
      instruments alone. The aim of this study was to investigate the feasibility of
      transvaginal NOTES gastrectomy with the use of an extra endoscope as a retracting
      device of the stomach. METHODS: This acute in vivo feasibility study was
      performed under the approval of the Institutional Animal Care and Use Committee
      (IACUC). Four female 40-kg pigs received general anesthesia and underwent
      transvaginal endoscopic partial gastrectomy. Under laparoscopic guidance, the
      uterus was fixed anteriorly and transvaginal access was established in a standard
      fashion. The perigastric ligaments were dissected with needle knife/insulation
      tipped electrosurgical knife (IT) via transvaginally placed double-channel
      endoscope. This step was assisted with the second, CO(2)-insufflating endoscope
      advanced in the stomach (i.e., so-called endoscopic gastric control). A linear
      stapling device with a flexible shaft was then passed transvaginally, and the
      anterior gastric wall was partially resected. The specimen was isolated and
      retrieved through the vagina. Concluding endoscopy was carried out to confirm the
      absence of mucosal damage due to endoscopic gastric control. This was further
      confirmed at necropsy immediately after sacrifice. RESULTS: All animals underwent
      successful transvaginal NOTES gastrectomy. Endoscopic gastric control greatly
      facilitated perigastric dissection by providing appropriate tissue
      countertraction on the ligaments. Use of transabdominal (laparoscopic) graspers
      was thus minimized. There were no intraoperative complications directly related
      to use of the primary (transvaginal) endoscope or the additional (gastric)
      endoscope. Distention of downstream bowel after gastric insufflation was minimal
      with CO(2). No major injuries were noted on gastric mucosa at postmortem
      investigations. CONCLUSIONS: Transvaginal NOTES partial gastrectomy is feasible
      in porcine models. Use of an extra endoscope to retract the stomach is effective
      to minimize transabdominal assistance. Further studies on human subjects are
      necessary to establish this as a safe and attractive ancillary technique in
      NOTES.

PMID- 18814000
TI  - Total laparoscopic ileal pouch-anal anastomosis: prospective series of 82
      patients.
AB  - BACKGROUND: Ileal pouch-anal anastomosis (IPAA) is the recommended procedure for
      ulcerative colitis and profuse familial adenomatous polyposis. The aims of this
      study were to report a consecutive series of 82 unselected patients who undergone
      a total laparoscopic IPAA with a special focus on the postoperative morbidity and
      1-year functional results. METHODS: Between 2002 and 2008, 82 consecutive
      patients undergoing IPAA under a total laparoscopic approach were enrolled.
      Patient data, surgical procedure, and 1-year functional outcome were analyzed.
      RESULTS: Among the 82 patients, 44 (54%) had a former subtotal colectomy (STC)
      before IPAA. No patient died postoperatively. Conversion rate was 11%. Overall
      morbidity was 32%. Symptomatic anastomotic fistulas were observed in nine
      patients (10%). Reoperation was needed in 5/82 (6%) of the patients. One-year
      functional results were 4.7 +/- 1.9 during the day and 1 +/- 1.2 during the
      night. Operating time decreased significantly after the first 40 laparoscopic
      IPAA (p = 0.0183). No difference was observed in the morbidity and functional
      results between patients operated for IPAA after a former colectomy or during a
      restorative proctocolectomy. CONCLUSIONS: This study suggested the feasibility
      and safety of the total laparoscopic approach IPAA. Total laparoscopic approach
      could become the best approach for IPAA. Prior colectomy does not modify the
      result of this demanding surgical procedure.

PMID- 18814001
TI  - Simulation in laparoscopic surgery: a concurrent validity study for FLS.
AB  - BACKGROUND: Current assessments using the fundamentals of laparoscopic surgery
      (FLS) tasks are labour intensive and depend heavily on expert raters. Hand motion
      analysis may offer an alternative method of objective evaluation of FLS
      performance. PURPOSE: The aim of this study was to assess whether a correlation
      exists between the expert rated assessments of the FLS tasks and computer-based
      assessment of motion efficiency using the Imperial College surgical assessment
      device (ICSAD). METHODS: We recruited 26 volunteer subjects who were stratified
      into three experience groups: juniors (PGY1-3) (N = 13), seniors (PGY4,5) (N = 7)
      and staff surgeons (N = 6). All subjects performed four FLS tasks: (1) peg
      transfer, (2) pattern cut, (3) endoloop and (4) intracorporeal suturing.
      Performance was assessed by both standard FLS expert rating and motion analysis
      using ICSAD. Group differences were analyzed using the Kruskal-Wallis test, and
      Spearman coefficient analyses were employed to compare FLS and ICSAD scores.
      RESULTS: FLS expert-derived scores discriminated effectively between experience
      groups for all tasks (p < 0.05). Motion efficiency scores discriminated between
      experience groups for tasks 1, 3 and 4 for number of movements (p < 0.05), tasks
      1 and 4 for total distance (p < 0.05) and tasks 1, 2, 3 and 4 for total time (p <
      0.005). There was a significant correlation between total FLS expert scores and
      the motion efficiency metrics of total distance, number of movements and total
      time (Spearman coefficient and p values of 0.81, < 0.001; 0.76; < 0.001; and
      0.93, < 0.001, respectively). CONCLUSION: There is a high correlation between FLS
      standard scoring and motion efficiency metrics. The use of ICSAD for the
      objective assessment of FLS tasks may in the future offer an adjunctive method of
      evaluation. ICSAD metrics are potentially less labour intensive due to the
      instant and fully automated computerized scoring that it provides.

PMID- 18814002
TI  - Robot-assisted laparoscopy in gynecologic oncology.
AB  - OBJECTIVES: The aim of this prospective study was to evaluate the feasibility and
      the outcome of gynaecological cancer surgery with the Da Vinci S surgical system
      (Intuitive Surgical). METHODS: From February 2007 to September 2007, 28 patients
      underwent 32 gynaecological procedures in a single centre. Surgical procedures
      consisted of total hysterectomy, bilateral oophorectomy, and pelvic and/or lombo
      aortic lymphadenectomy. In all cases, surgery was performed using both
      laparoscopic and robot-assisted laparoscopic techniques. In this heterogeneous
      series, a subgroup of 12 patients treated for advanced cervical cancer was
      compared with a retrospective series of 20 patients who underwent the same
      surgical procedure by laparotomy. RESULTS: Mean age of the entire population was
      52.5 years (range 25-72 years) and mean body mass index (BMI) was 25 kg/m(2)
      (range 18-40 kg/m(2)). Indications for surgery were cervical cancer in 21 cases,
      endometrial cancer in 7 cases, ovarian cancer in 1 case and cervical dysplasia in
      3 cases. Median operating time was 180 min (mean 175.25 min, range 80-360 min)
      and median estimated blood loss was 110 cc (range 0-400 cc); no transfusions were
      necessary. No perioperative complications were observed and median time of
      hospitalisation was 3 days (mean 3.9 days, range 2-8 days). In the subgroup of 12
      advanced cervical cancer a significant difference was observed in terms of
      hospital stay compared with laparotomy; no difference was observed concerning
      operative time. Fewer complications were observed with laparotomy (33% versus
      25%) but more serious complications than with robot-assisted laparoscopy.
      CONCLUSION: As suggested in the literature, the use of robot-assisted laparoscopy
      leads to less intraoperative blood loss, less post operative pain and shorter
      hospital stays compared with those treated by more traditional surgical
      approaches. Despite the need for more extensive studies, robot-assisted surgery
      seems to represent a similar technological evolution as the laparoscopic approach
      50 years ago.

PMID- 18814003
TI  - Laparoscopic left lobe liver resection in a porcine model: a study of the
      efficacy and safety of different surgical techniques.
AB  - INTRODUCTION: Laparoscopic liver surgery is evolving and the best technique for
      dividing the liver parenchyma is currently under debate. The aim of this study
      was to study different techniques during a full laparoscopic lobe resection, and
      determine the efficacy and risks of bleeding and gas embolism. METHODS: Sixteen
      pigs were randomized to two groups: group US underwent an operation with
      Ultracision shears (AutoSonix) and ultrasonic dissector (CUSA) and group VS with
      a vessel sealing system (Ligasure) and ultrasonic dissector. A left lobe
      resection was performed. Transesophageal endoscopic echocardiography (TEE) was
      used to detect gas emboli in the right side of the heart and pulmonary artery.
      The operations and TEE were recorded for later assessment. RESULTS: Compared with
      group VS, group US exhibited significantly more intraoperative bleeding (p =
      0.02), a trend towards a longer operation time (p = 0.08), and a trend towards
      more embolization for grade I emboli. In total, 10 of 15 animals had emboli
      during the operation. CONCLUSIONS: This study showed that a laparoscopic left
      lobe resection can be performed with a combination of AutoSonix and CUSA as well
      as with Ligasure and CUSA instrumentation. In our hands, less bleeding was
      incurred with Ligasure than with AutoSonix.

PMID- 18814004
TI  - Laparoscopic approach to esophageal perforation secondary to pneumatic dilation
      for achalasia.
AB  - BACKGROUND: Perforation of the esophagus after pneumatic dilation for achalasia
      is a severe complication which should be treated accurately in order to obtain a
      successful immediate outcome and a satisfactory result for the underlying
      condition. METHODS: Five consecutive patients presenting with distal esophageal
      perforation after pneumatic dilation for achalasia were included in this study.
      All patients had gastrografin swallow performed to confirm the perforation, and
      one patient was also submitted to flexible esophagoscopy. Laparoscopic approach
      was performed in all patients with five portals. The phrenoesophageal membrane
      was opened on its anterior aspect. The distal esophagus was dissected free, and
      perforations were identified with the help of methylene blue or milk
      administration through the esophageal tube. All perforations were sutured with
      interrupted absorbable sutures. Contralateral myotomy and partial anterior Dor
      fundoplication completed the operation. Endoscopic control of length of myotomy
      and watertightness of mucosal closure was performed in all cases. RESULTS: There
      were no intraoperative complications. After surgery all patients were maintained
      with nil per os until a barium swallow showed no leakage. One patient had a
      radiologic leakage sustained for 1 week. All patients were dismissed
      uneventfully. At 6 months after surgery, esophageal manometry was performed. Mean
      lower esophageal sphincter resting pressure had fallen from 30 to 8.7 mmHg.
      CONCLUSIONS: Laparoscopy offers an excellent approach to treat distal esophageal
      instrumental perforations, perhaps even better than open surgery. Suture of the
      perforation, contralateral myotomy and partial anterior fundoplication is a good
      option in the treatment of perforated achalasia after pneumatic dilation.

PMID- 18814005
TI  - Two-stage laparoscopic biliopancreatic diversion with duodenal switch as
      treatment of high-risk super-obese patients: analysis of complications.
AB  - INTRODUCTION: The aim of this study is to retrospectively analyze the incidence
      of complications after two-stage laparoscopic biliopancreatic diversion with
      duodenal switch (Lap BPD-DS) in high-risk super-obese patients and explore the
      possible predictive factors of specific complications after laparoscopic sleeve
      gastrectomy (SG). METHODS: High-risk patients--body mass index (BMI) > 50 kg/m(2)
      with at least two major comorbidities: type 2 diabetes, obstructive sleep apnea
      syndrome (OSAS), hypertension--undergoing two-stage laparoscopic BPD-DS were
      retrospectively analysed. The SG pouch volume was 100-150 ml; in the second
      stage, the common channel and the alimentary loop were 100 cm and 150 cm,
      respectively. RESULTS: Eighty-seven patients (50 female, 57.5%) underwent SG (two
      open). The mean age was 41.8 +/- 10.22 years with BMI of 55.2 +/- 6.69 kg/m(2).
      Four patients had Prader-Willy syndrome. Fourteen (16.46%) patients (6 female,
      42.8%) had postoperative complications such as bleeding, fistula, pulmonary
      embolism, transitory acute renal failure, and abdominal abscess. One patient died
      at postoperative day 5 of pulmonary embolism. One patient was reoperated for
      hemoperitoneum by laparoscopy. The risk of complications after SG was lower in
      patients where reinforcement of the suture line was used (0.492), while it was
      higher in men (1.780). Neither difference was statistically significant [p = not
      significant (NS)]. After 9-24 months, 27 patients (BMI 43 +/- 8 kg/m(2))
      underwent a second stage of BPD-DS (two open). Major postoperative complications
      were registered in eight patients (29.6%): three bleeding, four duodeno-ileal
      stenosis and one rhabdomyolysis. Two cases of internal hernia required
      laparoscopic reoperation. The reoperation rate was 1/85 (1.2%) after SG and 2/27
      (7.4%) after second stage. CONCLUSIONS: Complications after SG greatly decrease
      after the learning curve period and can be successfully managed without need of
      reoperation. Suture-line reinforcement, at least selectively in the middle-upper
      portion of the staple line and in super-super-obese patients, is recommended to
      decrease the incidence of specific complications.

PMID- 18814006
TI  - Effect of Reteplase and PAI-1 antibodies on postoperative adhesion formation in a
      laparoscopic mouse model.
AB  - BACKGROUND: Postoperative adhesions remain an important clinical problem,
      accounting for infertility, chronic pain and bowel obstruction. Its prevention is
      still inadequate and overall poorly understood. The aim of this study was to
      investigate the effect of Reteplase (a recombinant plasminogen activator, r-PA)
      and of PAI-1 antibodies upon adhesion formation in a laparoscopic model. METHODS:
      Pneumoperitoneum-enhanced adhesions were induced by performing a bipolar lesion
      in female BALB/c mice and by using pure and humidified CO(2) as insufflation gas
      for 60 min. In experiment 1, four doses of 0.125, 0.25, 0.5 and 1 mg/0.5 ml r-PA
      and one and two doses of 1 mg r-PA were administrated i.p. Two control groups
      were included, one without any treatment and the second one receiving four times
      0.5 ml of saline. In experiment 2, four doses of 0, 1, 10 and 100 microg/0.5 ml r
      PA were administrated i.p. In experiment 3, PAI-1 neutralising and non
      neutralising antibodies were injected i.p. after performing the lesion on day 0
      and days 2 and 4. Adhesions were scored after 7 days. RESULTS: Adhesion formation
      was less with the administration of four doses of 1 microg r-PA (proportion, p <
      0.04, Wilcoxon). An increase in adhesion formation was observed when higher
      number of doses and amounts of r-PA were used (Proc GLM, eight groups, two
      variables, p = 0.05 for the amount of r-PA and p < 0.02 for the number of doses
      administrated). No effect was observed with the PAI-1 antibodies. CONCLUSIONS:
      Low-dose i.p. administration of rPA is effective in the prevention of adhesions
      in a laparoscopic mouse model.

PMID- 18814007
TI  - Laparoscopic versus open liver segmentectomy: prospective, case-matched,
      intention-to-treat analysis of clinical outcomes and cost effectiveness.
AB  - INTRODUCTION: Reduction in hospital stay, blood loss, postoperative pain and
      complications are common findings after laparoscopic liver resection, suggesting
      that the laparoscopic approach may be a suitable alternative to open surgery.
      Some concerns have been raised regarding cost effectiveness of this procedure and
      potential implications of its large-scale application. Our aim has been to
      determine cost effectiveness of laparoscopic liver surgery by a case-matched,
      case-control, intention-to-treat analysis of its costs and short-term clinical
      outcomes compared with open surgery. METHODS: Laparoscopic liver segmentectomies
      and bisegmentectomies performed at Ninewells Hospital and Medical School between
      2005 and 2007 were considered. Resections involving more than two Couinaud
      segments, or involving any synchronous procedure, were excluded. An operation
      magnitude-matched control group was identified amongst open liver resections
      performed between 2004 and 2007. Hospital costs were obtained from the Scottish
      Health Service Costs Book (ISD Scotland) and average national costs were
      calculated. Cost of theatre time, disposable surgical devices, hospital stay, and
      high-dependency unit (HDU) and intensive care unit (ICU) usage were the main
      endpoints for comparison. Secondary endpoints were morbidity and mortality.
      Statistical analysis was performed with Student's t-test, chi(2) and Fisher exact
      test as most appropriate. RESULTS: Twenty-five laparoscopic liver resections were
      considered, including atypical resection, segmentectomy and bisegmentectomy, and
      they were compared to 25 matching open resections. The two groups were
      homogeneous by age, sex, coexistent morbidity, magnitude of resection, prevalence
      of liver cirrhosis and indications. Operative time (p < 0.03), blood loss (p <
      0.0001), Pringle manoeuvre (p < 0.03), hospital stay (p < 0.003) and
      postoperative complications (p < 0.002) were significantly reduced in the
      laparoscopic group. Overall hospital cost was significantly lower in the
      laparoscopic group by an average of 2,571 pounds sterling (p < 0.04).
      CONCLUSIONS: Laparoscopic liver segmentectomy and bisegmentectomy are feasible,
      safe and cost effective compared to similar open resections. Large-scale
      application of laparoscopic liver surgery could translate into significant
      savings to hospitals and health care programmes.

PMID- 18814008
TI  - The Plicator procedure for the treatment of gastroesophageal reflux disease: a
      registry study.
AB  - BACKGROUND: Endoscopic full-thickness plication of the gastric cardia using the
      Plicator is shown to be effective for the treatment of symptomatic
      gastroesophageal reflux disease (GERD) in both prospective and randomized
      controlled trials. This registry study aimed to evaluate Plicator procedure
      safety and efficacy among GERD patients treated in routine clinical practice at
      multiple academic and nonacademic centers. METHODS: An open-label, prospective
      multicenter trial was conducted at seven centers under institutional review board
      approval. Patients with symptomatic GERD completed a series of questionnaires at
      baseline to assess GERD symptoms, heartburn/regurgitation scores, antisecretory
      medication use, and treatment satisfaction. All the patients then underwent the
      Plicator procedure with placement of a single transmural pledgeted suture in the
      anterior gastric cardia. The patients were reevaluated at 12 months after
      plication. RESULTS: The 12-month follow-up assessment was completed by 81
      patients. At 12 months, the mean GERD Health-Related Quality-of-Life score had
      improved significantly compared with the baseline score (12.0 vs 26.6; p <
      0.001), with 66% of the subjects showing an GERD-HRQL score improved 50% or more.
      Statistically significant improvements also were observed in median heartburn and
      regurgitation symptom scores. At 12 months, the need for daily proton pump
      inhibitor (PPI) therapy was eliminated for 58% of the patients. At baseline, 18%
      of the subjects had been satisfied with their GERD symptom control while on
      antisecretory therapy. At 12 months, 75% of the patients were satisfied with
      their GERD symptom control after undergoing the Plicator procedure, and 86% would
      recommend the procedure to family or friends. There were no serious adverse
      events and no late onset of any adverse events. CONCLUSIONS: In this multicenter
      study, the Plicator procedure effectively improved GERD quality-of-life scores,
      reduced GERD symptoms and medication use, and yielded higher treatment
      satisfaction than with the use of chronic antisecretory therapy. These effects
      all were seen 12 months after plication, and no major adverse effects were
      observed.

PMID- 18814009
TI  - Sexual function after sacrospinous fixation for vaginal vault prolapse: bad or
      mad?
AB  - BACKGROUND: The main indication for sacrospinous ligament suspension is to
      correct either total procidentia, a posthysterectomy vaginal vault prolapse with
      an associated weak cardinal uterosacral ligament complex, or a posthysterectomy
      enterocele. This study aimed to evaluate sexual function and anatomic outcome for
      patients after sacrospinous ligament suspension. METHODS: For this study, 52
      patients who had undergone sacrospinous ligament fixation during the preceding 5
      years were asked to complete the Female Sexual Function Index (FSFI)
      questionnaire. The patients were vaginally examined using the ICS POP score, and
      the results were compared with their preoperative status. For statistical
      analysis, GraphPad for Windows, version 4.0, was used. RESULTS: The 52 patients
      were examined during a follow-up period of 38 months. No major intraoperative
      complications were noted. Recurrence of symptomatic apical descent was noted in
      6% of the patients and de novo prolapse in 13.5%. Only one patient was
      symptomatic. Three patients experienced de novo dyspareunia, which resolved in
      two cases after stitch removal. Sexual function was good, rating higher than
      three points for each of the domains including satisfaction, lubrication, desire,
      orgasm, and pain. CONCLUSION: Sacrospinous ligament fixation still is a valuable
      option for the treatment of vaginal vault prolapse. Sexual function is
      satisfactory, with few cases of de novo dyspareunia.

PMID- 18814010
TI  - Effect of laparoscopic grasper force transmission ratio on grasp control.
AB  - BACKGROUND: Surgeons may cause tissue damage by incorrect laparoscopic pinch
      force control. Unpredictable tissue and grasper properties may cause slips or
      ruptures. This study investigated how different forms of haptic feedback
      influence the surgeon's ability to generate a safe laparoscopic grasp while
      pulling tissues of variable stiffness using graspers with different force
      transmission ratios. The results will help define design requirements for
      training facilities and instruments. METHODS: For this study, 10 participants
      lifted an object barehanded, with tweezers, or with one of two laparoscopic
      graspers until they where able to complete five consecutive safe lifts under
      different tissue stiffness conditions. The participants were presented with
      indirect visual feedback of pinch force, object location, and target location.
      RESULTS: Lifting with instruments (tweezers or graspers) required 4.5 to 14.5
      times as many practice trials as barehanded lifting, where no slips were
      recorded. Additionally, slips occurred more often with a decreasing force
      transmission ratio of the graspers and with increasing tissue stiffness. The
      maximal pinch force was higher in lifting with instruments than in barehanded
      lifting (26-60%) irrespective of the stiffness conditions. Using a grasper, the
      slip margin often was not high enough in the stiffest condition, resulting in
      slippage of up to 84%. CONCLUSIONS: Without the direct tactile feedback that
      occurs with normal skin-tissue contact, subjects using graspers have trouble
      anticipating slippage when lifting tissue with variable stiffness. Performance
      drops with a decreased force transmission ratio of the instrument and increased
      tissue stiffness. Furthermore, the pinch forces are not adapted to the variable
      stiffness conditions. The same pinch force is applied irrespective of tissue
      stiffness. It takes participants longer to learn a safe laparoscopic grasp than
      to learn barehanded lifts. Additionally, to perform safe laparoscopic surgery,
      care should be taken when graspers with a low force transmission ratio are used.

PMID- 18814011
TI  - Multimedia article. Upper mediastinal lymph node dissection for esophageal cancer
      through a thoracoscopic approach.

PMID- 18814012
TI  - Functional luminal imaging probe geometric and histomorphologic analysis of
      abdominal wall wound induced by different trocars in pigs.
AB  - BACKGROUND: This study aimed to investigate wound geometry and tissue damage
      caused by several different trocar types using a quantitative functional luminal
      imaging probe (FLIP) geometric profile and histomorphologic analysis. METHODS:
      Four pigs were used in this study. After general anesthesia, six different
      trocars were randomly inserted at preselected locations in the porcine abdominal
      wall. The hydration status of the animals was monitored and maintained. A bag
      mounted on a FLIP was used to profile the geometry of the trocar holes during
      distension. After the FLIP study, the abdominal wall surrounding the trocar holes
      was harvested. The tissue was fixed in neutral 10% buffered formalin solution for
      more than 24 h. The samples contained control tissue (undamaged) and test tissue
      (damaged) through the entire rectangular tissue block. Approximately four to
      seven slides were cut parallel to the surface from each sample. Each slide was
      photographed, and the morphometry of the hole and damaged areas were measured and
      displayed three-dimensionally. The histologic sections were analyzed with regard
      to acute damage, bleeding, and acute inflammation of the skin, muscle, and
      fascia. RESULTS: The FLIP study demonstrated differences between the six trocars.
      These were mainly due to differences between the Versaport Plus V2 bladed trocar
      with the smooth cannula, the Applied Medical Separator nonbladed access system
      with threaded cannula, and the VersaStep Plus trocar. The morphometry data showed
      the smallest hole and damage areas for the Versaport Plus V2 bladed trocar with
      the smooth cannula. The damaged area divided by the trocar hole area was smallest
      for the VersaStep plus trocar and the Ethicon Endopath bladed trocar with a
      stability cannula (p < 0.05). The histologic analysis showed that the VersaStep
      Plus trocar and the Ethicon Endopath bladed trocar with a stability cannula gave
      the least bleeding and inflammation (p < 0.05). CONCLUSION: An agreement was
      found between the geometric data obtained by FLIP, the morphometric analysis, and
      the histology.

PMID- 18814013
TI  - Laparoscopic hernia repair with the patient under combined spinal epidural
      anesthesia: cardiac arrest.

PMID- 18814014
TI  - The role of diagnostic laparoscopy for acute abdominal conditions: an evidence
      based review.
AB  - Diagnostic laparoscopy is minimally invasive surgery for the diagnosis of
      intraabdominal diseases. This study aim was a critical examination of the
      available literature on the role of laparoscopy for the diagnosis and treatment
      of acute intraabdominal conditions. A systematic literature search of English
      language articles on MEDLINE, the Cochrane database of evidence-based reviews,
      and the Database of Abstracts of Reviews of Effects was performed for the period
      1995-2006. The level of evidence in the identified articles was graded. This
      review examines the role of diagnostic laparoscopy for acute nonspecific
      abdominal pain, trauma, and the acute abdomen experienced by the critically ill
      patient. The indications, contraindications, risks, benefits, diagnostic accuracy
      of the procedure, and associated morbidity are discussed. The limitations of the
      available literature are highlighted, and evidence-based recommendations for the
      use of diagnostic laparoscopy to determine acute intraabdominal conditions are
      provided.

PMID- 18814015
TI  - Natural orifice translumenal endoscopic surgery (NOTES) applied totally to
      sigmoidectomy: an original technique with survival in a porcine model.
AB  - BACKGROUND: Natural orifice translumenal endoscopic surgery (NOTES) continues to
      evolve. This study investigated the feasibility and outcome of performing
      localized sigmoidectomy in its entirety via NOTES. METHODS: A survival study of
      five male minipigs (mean weight, 30 kg) was conducted. After anesthesia, a
      gastrotomy was created by a per os double-channel endoscope, and full
      peritoneoscopy was performed. A Berci needle then was inserted transparietally to
      allow maintenance and monitoring of the pneumoperitoneum. Using a transanal probe
      to facilitate intestinal retraction, the mesentery was dissected with instruments
      worked through the channels of the transgastric endoscope. The anvil of a
      circular stapler then was passed per anum into the colon above the point of
      intended transection. A penetrating transrectal trocar was placed to allow entry
      of a linear stapler into the peritoneum through a colotomy, and the sigmoid was
      cross-stapled proximally. The strut of the anvil then was snugged into a colotomy
      made at this staple line. The specimen was delivered via the anus by a "pull
      through" technique. The distal sigmoidal margin was cross-stapled
      extracorporeally, ensuring that the colotomy was included within the specimen.
      Retrograde passage of the circular stapler head per anus allowed colocolonic
      reanastomosis by its mating with the anvil already in situ. The gastrotomy was
      closed with a previously validated prosthesis. Postoperatively, all the animals
      were recovered and monitored for well-being during convalescence. Endoscopy
      (gastroscopy and sigmoidoscopy), laparoscopy, and laparotomy were performed on
      postoperative day 14 as follow-up measures. RESULTS: Each operation was
      satisfactorily completed. The mean operative time was 76 min (range, 44-95 min).
      All the animals prospered postoperatively. Follow-up examination showed full
      healing of all anastomoses and gastrotomy sites. There was no evidence of luminal
      stricturing, peritonitis, or intraabdominal sepsis in any animal. CONCLUSIONS:
      Using this experimental model, colonic resection and reanastomosis can be
      performed safely within the NOTES format.

PMID- 18814016
TI  - Epidural analgesia diminished pain but did not otherwise improve enhanced
      recovery after laparoscopic sigmoidectomy: a prospective randomized study.
AB  - BACKGROUND: The primary hypothesis for this study was that epidural analgesia
      reduces the use of opioids and thus advances bowel function and oral intake and
      shortens hospital stay after laparoscopic sigmoidectomy performed according to
      principles of enhanced recovery after surgery. METHODS: For this study, 60
      patients with complicated diverticular disease were randomized to the epidural
      anesthesia group or the control group before surgery. Postoperative oxycodone
      consumption, pain, and recovery parameters were followed for 14 days. RESULTS:
      The epidural group needed less oxycodone than the control group until 12 h
      postoperatively. They experienced significantly less pain related to coughing and
      motion until postoperative day 2. In the epidural group, fewer patients
      experienced significant pain, and the duration of postoperative pain was shorter.
      Postoperative oral intake, bowel function, hospital stay, and overall
      complication rate were similar in the two groups. However, the control group had
      more postoperative hematomas. CONCLUSIONS: Epidural analgesia significantly
      alleviates pain, reducing the need for opioids during the first 48 h after
      laparoscopic sigmoidectomy. However, epidural analgesia does not alter
      postoperative oral intake, mobilization, or length of hospital stay.

PMID- 18814017
TI  - Characterization and its potential application of two esterases derived from the
      arctic sediment metagenome.
AB  - Two esterase genes (designated as estAT1 and estAT11, respectively) were cloned
      by activity-based screening of a fosmid library constructed with seashore
      sediment sample of the Arctic. The sequence analysis of the genes revealed that
      these esterase genes encoded proteins of 303 and 312 amino acids, respectively,
      and showed 40-50% identities to members of the hormone-sensitive lipase (HSL)
      family retaining a catalytic triad with a conserved GDSAG sequence and an
      oxyanion hole (HGGG). The esterases genes were overexpressed in Escherichia coli
      by co-expressing GroEL-GroES chaperonine, and the recombinant proteins (rEstAT1
      and rEstAT11) were purified to homogeneity. The purified EstAT1 and EstAT11 were
      active in a broad range of temperature from 20 to 40 degrees C with an optimum
      temperature at 30 degrees C. The activation energies of rEstAT1 and rEstAT11 to
      hydrolyze p-nitrophenyl esters of butyrate were determined to be 12.65 kcal/mol
      and 11.26 kcal/mol, respectively, indicating that they are cold-adapted
      esterases. The purified EstAT1 and EstAT11 could hydrolyze racemic ofloxacin
      esters, and further rEstAT11 hydrolyzed preferentially (S)-racemic ofloxacin
      butyl ester with an enantiomeric excess (ee(p)) value of 70.3%. This work
      represents an example that develops enzymes from the Arctic using metagenomic
      approach, potentially applicable to chiral resolution of heat-labile substrates.

PMID- 18814018
TI  - Local cooling provides muscle flaps protection from ischemia-reperfusion injury
      in the event of venous occlusion during the early reperfusion period.
AB  - Clinicians often place patients in heated rooms following muscle flap transfers.
      We hypothesize that exposure of flaps to heated room temperatures could result in
      an unnecessary hyperthermic ischemic insult if the flaps were to be compromised
      by venous outflow obstruction, while exposure of elective flaps to local cooling
      during early perfusion may provide protection in the event of venous occlusion.
      The rat rectus femoris muscle flap was elevated and clamped for 1 h. The muscle
      was then exposed to various temperatures for 1 h of perfusion followed by
      complete venous occlusion for 3 h. Occlusion clamps were removed and flaps were
      allowed to reperfuse for 24 h. Flaps were assessed for muscle necrosis and edema.
      Venous occluded muscles demonstrated decreased muscle necrosis and edema in the
      locally cooled group (8.5 +/- 6.7%, 3.06 +/- 0.14; P < 0.001) compared to the
      room temperature group (76.2 +/- 23.0%, 3.73 +/- 0.13), and the local warming
      group (97.3 +/- 1.4%, 3.84 +/- 0.29) respectively. No difference was noted in
      muscle necrosis nor edema amongst non-ischemic muscles irrespective of
      temperature exposure. These results suggest a beneficial role for exposure of
      elective flaps to local cooling during the early perfusion period in order to
      provide protection from ischemia reperfusion injury in the event of a venous
      occlusion insult. The prophylactic exposure of flaps to local cooling is further
      supported by the lack of a harmful effect when flaps were not compromised by
      venous occlusion.

PMID- 18814019
TI  - Effect of porcine brain growth factor on primary cell cultures and BHK-21 [C-13]
      cell line.
AB  - Growth factors from neural tissues have been described as potent mitogens for a
      wide variety of mesoderm- and ectoderm-derived cells in vitro. We used porcine
      brain extract for in vitro testing of proliferation properties on primary ovarian
      cells, uterine cells, and cardiomyocytes in culture as well as for BHK-21 [C-13]
      cell line. The addition of this extract accelerates proliferation in all examined
      cultures. It also lowers serum requirement and shortens the cultivation period
      for BHK-21 [C-13] cells. Fibroblast growth factors from brain of different
      species, but not porcine, are already characterized and their proliferative
      effect proved. Therefore, we purified, determined, and confirmed the presence of
      basic fibroblast growth factor in porcine brain extract by Western blot analysis
      and showed its biological activity on BHK-21 [C-13] cells.

PMID- 18814020
TI  - Safety and efficacy of Privigen, a novel 10% liquid immunoglobulin preparation
      for intravenous use, in patients with primary immunodeficiencies.
AB  - PURPOSE: The present study was designed to evaluate the efficacy and safety of a
      novel, 10% liquid formulation of intravenous immunoglobulin, stabilized with 250
      mmol/L L-proline (Privigen), in patients with primary immunodeficiency disease.
      MATERIALS AND METHODS: Eighty adults and children diagnosed with common variable
      immunodeficiency or X-linked agammaglobulinemia received intravenous Privigen
      infusions (200-888 mg/kg) at 3- or 4-week intervals over a 12-month period,
      according to their previously established maintenance dose. The primary endpoint
      was the annual rate of acute serious bacterial infections. RESULTS: There were
      six episodes of acute serious bacterial infections, corresponding to an annual
      rate of 0.08; the annual rate for all infections was 3.55. Mean serum IgG trough
      levels were between 8.84 and 10.27 g/L. A total of 1,038 infusions were
      administered, most of them at the maximum rate permitted (8.0 mg kg(-1) min(-1)).
      Temporally associated adverse events, possibly or probably related to study drug,
      occurred in 9% of infusions, either during or within 72 h after infusion end.
      CONCLUSION: Privigen is well tolerated and effective for the treatment of primary
      immunodeficiency.

PMID- 18814021
TI  - Mitochondria in malaria and related parasites: ancient, diverse and streamlined.
AB  - Parasitic organisms have emerged from nearly every corner of the eukaryotic
      kingdom and hence display tremendous diversity of form and function. This
      diversity extends to their mitochondria and mitochondrion-derived organelles.
      While the principles of the chemiosmotic theory apply to all these pathogens, the
      differences from their hosts provide opportunities for therapeutic development.
      In this review we discuss examples of mitochondrial systems from a deep-branching
      phylum, Apicomplexa. Many important human pathogens, such as malaria parasites,
      belong to this phylum. Unique features of their mitochondria are validated
      targets for drugs that are selectively toxic to the parasites.

PMID- 18814022
TI  - Affect and sexual behavior in the transition to university.
AB  - This research applied a lifespan developmental framework to the study of sexual
      behavior among late adolescents by examining monthly covariations of penetrative
      and oral sex with positive and negative affect across the first year of
      university. Participants were 177 Canadian students who completed baseline
      questionnaires, followed by six monthly, web-based questionnaires assessing
      sexual behaviors and affect. Multilevel analyses revealed an average positive
      relation between oral sex and positive affect. Of six variables, five predicted
      individual differences in covariation between sex and affect: psychosocial
      maturity (immature and semi-mature status), attitudes toward sex, prior sexual
      experience, and living situation. During months when participants reported sexual
      behavior, psychosocially mature students reported more positive affect than did
      less mature students; students with more permissive attitudes reported more
      positive affect than did students with less permissive attitudes; students with
      no penetrative sexual experience reported more positive affect than students who
      had penetrative sexual experience; and living away from parents was associated
      with less negative affect. Implications for further study of sexual behavior from
      a developmental perspective are discussed.

PMID- 18814023
TI  - The effects of different concentrations of sodium selenite on the in vitro
      maturation of preantral follicles in serum-free and serum supplemented media.
AB  - PURPOSE: This study was to investigate the effect of sodium selenite (SS) on in
      vitro maturation of mouse preantral follicles. METHODS: The isolated preantral
      follicles were cultured in TCM 199 medium supplemented with different
      concentrations (0, 5, 10, 15 ng/ml) of SS and 3 mg/ml bovine serum albumin (BSA)
      or 5% Fetal Bovine Serum (FBS). The ovulation was induced by addition of 1.5
      IU/ml human chorionic gonadotropin. The size and development of follicles and
      oocytes were assessed by calibrated eyepiece. RESULTS: The survival rates of
      follicles in FBS supplemented groups containing 5 and 10 ng/ml SS (88.23%,
      90.83%) were higher than other groups (P < 0.05 and P < 0.001 respectively). The
      mean diameter of follicles (199.84 +/- 15.58 microm) and the percentage of MII
      oocyte (33.08%) were higher in FBS supplemented group containing 10 ng/ml SS (P <
      0.001). CONCLUSION: The sodium selenite and FBS improve the in vitro growth and
      maturation of mouse preantral follicles.

PMID- 18814024
TI  - The binding of donepezil with external mouth of K+-channels of molluscan neurons.
AB  - Earlier, we have shown a strong inhibitory effect of donepezil on K+-current of
      molluscan neurons (Solntseva et al., Comp Biochem Physiol 144, 319-326, 2007). In
      the present work, a possible interaction of donepezil with the external mouth of
      the channel was examined using, as a tool, tetraethylammonium (TEA), a classical
      antagonist of potassium channels. Experiments were conducted in isolated neurons
      of snail Helix aspersa using the two-microelectrode voltage-clamp technique. A
      high-threshold slow-inactivating K+-current involving Ca2+-dependent (I (C)) and
      Ca2+-independent (I (K)) components was recorded. The I (C) was estimated at 30
      mV, and I (K) at 100 mV. The IC(50) values for blocking effect of donepezil on I
      (C) varied from 5.0 to 8.9 microM in different cells. Corresponding values for I
      (K) varied from 4.9 to 9.9 microM. The IC(50) values for blocking effect of TEA
      on I (C) lied in the range of 200 to 910 microM, and on I (K) lied in the range
      of 100 to 990 microM. The comparison of the effects of donepezil and TEA on the
      same cells revealed significant correlation between IC(50) values of these
      effects. The value of Spearman coefficient of correlation (r) was 0.77 for I (C)
      (P < 0.05), and 0.82 for I (K) (P < 0.05). In the presence of TEA, the effect of
      donepezil, both on I (C) and I (K), appears significantly weaker than in control
      solution. Dose-response curves of donepezil effect both on I (C) and I (K) were
      shifted right along horizontal axis when donepezil was applied in combination
      with TEA. Results suggest that TEA interferes with donepezil and precludes the
      occupation by donepezil of its own site. We suppose that the site for donepezil
      is situated near the TEA site with possible overlap.

PMID- 18814025
TI  - L-carnitine blood levels and oxidative stress in treated phenylketonuric
      patients.
AB  - AIMS: L-carnitine exerts an important role by facilitating the mitochondrial
      transport of fatty acids, but is also a scavenger of free radicals, protecting
      cells from oxidative damage. Phenylketonuria (PKU), an inborn error of
      phenylalanine (Phe) metabolism, is currently treated with a special diet
      consisting of severe restriction of protein-enriched foods, therefore potentially
      leading to L-carnitine depletion. The aim of this study was to determine L
      carnitine levels and oxidative stress parameters in blood of two groups of PKU
      patients, with good and poor adherence to treatment. METHODS: Treatment of
      patients consisted of a low protein diet supplemented with a synthetic amino
      acids formula not containing Phe, L-carnitine, and selenium. L-carnitine
      concentrations and the oxidative stress parameters thiobarbituric acid reactive
      species (TBARS) and total antioxidant reactivity (TAR) were measured in blood of
      the two groups of treated PKU patients and controls. RESULTS: We verified a
      significant decrease of serum L-carnitine levels in patients who strictly adhered
      to the diet, as compared to controls and patients who did not comply with the
      diet. Furthermore, TBARS measurement was significantly increased and TAR was
      significantly reduced in both groups of phenylketonuric patients relatively to
      controls. We also found a significant negative correlation between TBARS and L
      carnitine levels and a significant positive correlation between TAR and L
      carnitine levels in well-treated PKU patients. CONCLUSIONS: Our results suggest
      that L-carnitine should be measured in plasma of treated PKU patients, and when a
      decrease of this endogenous component is detected in plasma, supplementation
      should be considered as an adjuvant therapy.

PMID- 18814026
TI  - Silencing of estrogen receptor alpha (ERalpha) gene by promoter hypermethylation
      is a frequent event in Chinese women with sporadic breast cancer.
AB  - Usually, the function of estrogen receptor alpha (ERalpha) could be silenced by
      ERalpha gene promoter hypermethylation. However, frequency of ERalpha promoter
      methylation and the clinicopathological characteristics of ERalpha methylation in
      Chinese women with sporadic breast cancer are unknown. The aim of this study was
      to determine the methylation status of ERalpha promoter and its possible
      correlation with clinicopathological features in a series of 138 sporadic breast
      cancers in Chinese women. ER1, ER3, ER4, and ER5 primers were used for
      methylation-specific polymerase chain reaction (MSP) to analyze the CpG
      methylation of promoter region of ERalpha gene. In general, we found that ERalpha
      was methylated in 60.1% (83/138) tumors, including 57 of 69 ERalpha negative
      tumors (82.6%, P < 0.00001). Specifically within each region the methylation
      percentage of ER1, ER3, ER4 and ER5 were 34.8%, 35.5%, 39.1%, and 36.9%
      respectively. The degree of methylation at four CpG sites was higher in breast
      cancer compared with benign breast hyperplasia (P < 0.00001). In addition, the
      levels of ERalpha protein expression diminished with the frequency of ERalpha
      methylation (P < 0.0001, r = -0.469), the probability of methylation was
      increased for cases with ERalpha and PgR negativity (P < 0.00001). Our
      preliminary findings demonstrate, for what we believe to be the first time, that
      ERalpha methylation occurs in high frequency and is one of the mechanisms of
      ERalpha expression silence in a subset of sporadic breast cancers from Chinese
      women. Epigenetic alteration of the ERalpha gene may play an important role in
      the pathogenesis of breast cancer.

PMID- 18814027
TI  - Endothelial cell-laminin interaction: modulation of LDH expression involves
      alpha6beta4 integrin-FAK-p38MAPK pathway.
AB  - One of the possible mechanisms of the angiogenic effect of laminin (Ln) involves
      modulation of the biological activity of VEGF by regulating poly ADP ribosylation
      (PAR). PAR modification of VEGF was found to be related with the changes in
      NAD(+) associated with a shift in LDH isoenzymes. Further investigations on LDH
      gene expression in HUVECs suggested that the effect of Ln was mediated through
      alpha(6)beta(4) integrin-FAK-src-p38 MAPK pathway. This was evidenced by (a) co
      immunoprecipitation of beta(4) integrin with alpha(6) subunit, (b) activation by
      tyrosine phosphorylation of beta(4) integrin and FAK, (c) co-immunoprecipitation
      of FAK with beta(4) and with adapter protein, src, (d) increased phosphorylation
      of p38 MAPK in cells maintained on Ln and (e) blocking of effect of Ln on LDH-B
      gene expression by inhibition of p38 MAPK. Increase in serine phosphorylation of
      c-fos and c-jun and higher levels of heterodimers of AP-1 in the nucleus in cells
      maintained on Ln suggested activation of AP-1 transcription factor. These results
      provide evidence for modulation of endothelial cell function relevant to
      angiogenesis by Ln through alpha(6)beta(4) integrin.

PMID- 18814028
TI  - Language preference and perceptions of healthcare providers' communication and
      autonomy making behaviors among Hispanics.
AB  - BACKGROUND: To examine influence of language preference-English versus Spanish-on
      Hispanics' perceptions of their healthcare providers' communication behaviors.
      METHODS: Using the 2005 Medical Expenditure Panel Survey (MEPS), we observed non
      institutionalized Hispanics (n = 5197; US population estimate = 27,070,906), aged
      >or=18 years, reporting visiting a healthcare provider within the past 12 months.
      RESULTS: When compared to Spanish responders (reference group), English
      responders were more likely to report that their healthcare provider "always"
      listened to them carefully (adjusted odds ratio (OR) = 1.39, 95% confidence
      interval (CI) 1.09-1.78), "always" explained things so that they understood
      (adjusted OR 1.37, 95% CI 1.08-1.73), "always" spent enough time with them
      (adjusted OR = 1.62, 95% CI 1.24-2.11),"always" asked them to help make decisions
      (adjusted OR 1.37, 95% CI 1.03-1.82), and "always" showed respect for treatment
      decisions (adjusted OR = 1.66, 95% CI 1.27-2.19). DISCUSSION: Healthcare
      providers should consider the complex needs of Hispanic patients whose language
      of choice is not English.

PMID- 18814030
TI  - A risk and prevention counselor training program model: theory and practice.
AB  - The need for training mental health counselors in risk and prevention is
      presented, and justification of the development of an innovative and integrative
      prevention training program is offered. Theoretical underpinnings that connect
      the counseling discipline to the field of prevention are described. A risk and
      prevention training model from Harvard Graduate School of Education is presented
      as a case example that illustrates the integration of prevention practices into a
      counselor training curriculum. Prevention research initiatives are described as
      vehicles for interactive learning and training. Challenges and future
      opportunities for programmatic implementation are reviewed with attention towards
      systematic planning and program design.

PMID- 18814029
TI  - Coronary artery diseases in South Asian immigrants: an update on high density
      lipoprotein role in disease prevention.
AB  - Over the past several years, the overall prevalence and incidence of
      cardiovascular diseases (CVD) including coronary artery diseases (CAD) have
      declined in the United States (US) and in many developed countries. However,
      among South Asian in general and South Asian immigrants (SAIs) in particular, a
      disturbing trend toward high rates of CAD has been noted. This trend is
      associated with a high prevalence of conventional risk factors and metabolic
      syndrome in this population, yet these conventional risk factors may not account
      for the greater CAD risk among SAIs. A search for additional markers is
      warranted, to enable early detection and prevention of CAD in this high risk
      group. High density lipoprotein (HDL) is one of the predictor of CAD and is
      considered to be cardio-protective. However, some of the recent studies have
      shown that HDL is not only ineffective as an antioxidant but, paradoxically,
      appears to be pro-oxidant, and has been found to be associated with CAD. Such HDL
      is called dysfunctional HDL. We present here an overview CAD and CAD risk factors
      in general and dyslipidemias in particular in SAIs. In addition, the evolving
      theories on dysfunctional HDL and its impact on CAD are also briefly presented.

PMID- 18814031
TI  - From acquaintance to engagement: support in confronting primary prevention
      hassles.
AB  - For many students the importance of primary prevention is unquestionable.
      However, once they are exposed to the large number of problems that prevention
      practitioners and prevention scientists face, their preliminary enthusiasm
      decreases. It is suggested that in order to keep students' positive attitude
      toward primary prevention and to empower them professionally, exposure to six
      components is needed (e.g., personalizing prevention), resembling a relapse
      prevention activity.

PMID- 18814032
TI  - Machine vision based stochastic analysis of cancer cell mitochondrial dysfunction
      induced by a BH3 domain.
AB  - We have developed a versatile and rapid method for the quantitative estimation of
      cell death kinetics, following direct single-shot activation of the mitochondrial
      death pathway by a cell permeable BH3 activator peptide (D-R(8)BH3(BID)). This
      approach employs timelapse epifluorescent imaging of live cells and a machine-
      vision based feature extraction algorithm, to measure unidirectional stochastic
      transitions associated with mitochondrial inner membrane potential depolarization
      and/or permeability transition, at single cell resolution. This data is
      transformed to enable construction of a right step-wise survival function using
      the product limit estimator, and estimation of a median latency parameter
      (lambda), defined for the entire imaged cell population. Estimates of lambda
      computed for cells exhibiting two-colour fluorescence can be compared
      statistically using the Mantel-Hansel test. This general method has been applied
      to measure the kinetics and temporal ordering of BH3 domain induced mitochondrial
      depolarization and inner membrane permeabilization in cancer cells, and
      demonstrates the robustness of this technique in resolving temporally distinct
      intracellular events within individual cells.

PMID- 18814033
TI  - Critical issues in cultural neuropsychology: profit from diversity.

PMID- 18814034
TI  - Measurement in cross-cultural neuropsychology.
AB  - The measurement of cognitive abilities across diverse cultural, racial, and
      ethnic groups has a contentious history, with broad political, legal, economic,
      and ethical repercussions. Advances in psychometric methods and converging
      scientific ideas about genetic variation afford new tools and theoretical
      contexts to move beyond the reflective analysis of between-group test score
      discrepancies. Neuropsychology is poised to benefit from these advances to
      cultivate a richer understanding of the factors that underlie cognitive test
      score disparities. To this end, the present article considers several topics
      relevant to the measurement of cognitive abilities across groups from diverse
      ancestral origins, including fairness and bias, equivalence, diagnostic validity,
      item response theory, and differential item functioning.

PMID- 18814036
TI  - Severe hypernatraemia associated with growth hormone replacement therapy in a
      patient with septo-optic dysplasia.
AB  - BACKGROUND: The anti-natriuretic properties of growth hormone (GH) are well
      established. Growth hormone deficiency (GHD) results in salt and water depletion
      and studies confirm that replacement leads to sodium and vasopressin-mediated
      water retention in patients with intact posterior pituitary function. METHODS: We
      report the case of a 20-year-old male patient with septo-optic dysplasia, fixed
      cranial diabetes insipidus (DI) and an abnormal thirst threshold. With careful
      parental support, his sodium levels remained stable for many years on a fixed
      dose of DDAVP and a supervised fluid intake of 2.5 l/day. Several years after the
      original diagnosis, he was found to be ACTH deficient and following commencement
      of hydrocortisone replacement therapy became hypernatraemic. A new sodium
      homoeostasis was established with a higher dose of DDAVP. Subsequently, he
      developed symptoms typical of GHD and, after biochemical confirmation, GH
      replacement was commenced. RESULTS: There was an immediate clinical improvement
      (increased alertness, improved concentration) but severe hypernatraemia developed
      (peak 169 mmol/l) necessitating revision of his desmopressin and fluid intake
      regimen. CONCLUSION: Most GHD patients have intact posterior pituitary function.
      This case report highlights the powerful anti-natriuretic properties of GH.
      Endocrine physicians should be alert to this in patients with fixed DI and an
      abnormal thirst threshold.

PMID- 18814035
TI  - Exploring visual-spatial working memory: a critical review of concepts and
      models.
AB  - The ability to retain and process an object's identity and spatial location is
      essential for many daily tasks, often referred to as visual-spatial working
      memory. Research investigating visual-spatial processing has concentrated on
      three aspects or mechanisms thought to sub-serve this process; perceptual
      processes, anatomical correlates and working memory functions. An approach
      integrating all three areas has largely been neglected. Hence, this review sought
      to (1) outline some of the advances made to the understanding by these three
      concepts or models of visual-spatial processing, (2) establish the relationship
      between these processes, and discuss the challenges faced by researchers
      attempting to dissociate this functions from other visual-spatial processes as
      well as other working memory functions. It is suggested that a more comprehensive
      and integrative understanding of visual-spatial working memory has implications
      for research seeking to investigate visual-spatial memory, and to relate visual
      spatial memory to other cognitive functions, such as executive function and
      attention.

PMID- 18814037
TI  - A bayesian approach for quantifying trace amounts of antibody aggregates by
      sedimentation velocity analytical ultracentrifugation.
AB  - Sedimentation velocity analytical ultracentrifugation (SV-AUC) has become an
      important tool for the characterization of the purity of protein therapeutics.
      The work presented here addresses a need for methods orthogonal to size-exclusion
      chromatography for ensuring the reliable quantitation of immunogenic oligomers,
      for example, in antibody preparations. Currently the most commonly used approach
      for SV-AUC analysis is the diffusion-deconvoluted sedimentation coefficient
      distribution c(s) method, previously developed by us as a general purpose
      technique and implemented in the software SEDFIT. In both practical and
      theoretical studies, different groups have reported a sensitivity of c(s) for
      trace oligomeric fractions well below the 1% level. In the present work we
      present a variant of c(s) designed for the purpose of trace detection, with
      customized Bayesian regularization. The original c(s) method relies on maximum
      entropy regularization providing the most parsimonious distribution consistent
      with the data. In the present paper, we use computer simulations of an antibody
      system as example to demonstrate that the standard maximum entropy
      regularization, due to its design, leads to a theoretical lower limit for the
      detection of oligomeric traces and a consistent underestimate of the trace
      populations by approximately 0.1% (dependent on the level of regularization).
      This can be overcome with a recently developed Bayesian extension of c(s) (Brown
      et al., Biomacromolecules, 8:2011-2024, 2007), utilizing the known regions of
      sedimentation coefficients for the monomer and oligomers of interest as prior
      expectation for the peak positions in the distribution. We show that this leads
      to more clearly identifiable and consistent peaks and lower theoretical limits of
      quantization by approximately an order of magnitude for some experimental
      conditions. Implications for the experimental design of SV-AUC and practical
      detection limits are discussed.

PMID- 18814038
TI  - Mineralization of methyl tert-butyl ether and other gasoline oxygenates by
      Pseudomonads using short n-alkanes as growth source.
AB  - Biodegradation of methyl tert-butyl ether (MTBE) by cometabolism has shown to
      produce recalcitrant metabolic intermediates that often accumulate. In this work,
      a consortium containing Pseudomonads was studied for its ability to fully degrade
      oxygenates by cometabolism. This consortium mineralized MTBE and TBA with C3-C7 n
      alkanes. The highest degradation rates for MTBE (75 +/- 5 mg g(protein) (-1) h(
      1)) and TBA (86.9 +/- 7.3 mg g(protein) (-1) h(-1)) were obtained with n-pentane
      and n-propane, respectively. When incubated with radiolabeled MTBE and n-pentane,
      it converted more than 96% of the added MTBE to (14)C-CO(2). Furthermore, the
      consortium degraded tert-amyl methyl ether, tert-butyl alcohol (TBA), tert-amyl
      alcohol, ethyl tert-butyl ether (ETBE) when n-pentane was used as growth source.
      Three Pseudomonads were isolated but only two showed independent MTBE degradation
      activity. The maximum degradation rates were 101 and 182 mg g(protein) (-1) h(-1)
      for Pseudomonas aeruginosa and Pseudomonas citronellolis, respectively. The
      highest specific affinity (a degrees (MTBE)) value of 4.39 l g(protein) (-1) h(
      1) was obtained for Pseudomonas aeruginosa and complete mineralization was
      attained with a MTBE: n-pentane ratio (w/w) of 0.7. This is the first time that
      Pseudomonads have been reported to fully mineralize MTBE by cometabolic
      degradation.

PMID- 18814039
TI  - Evaluation of "alperujo" composting based on organic matter degradation,
      humification and compost quality.
AB  - The main by-product generated by the Spanish olive oil industry, a wet solid
      lignocellulosic material called "alperujo" (AL), was evaluated as a composting
      substrate by using different aeration strategies and bulking agents. The
      experiments showed that composting performance was mainly influenced by the type
      of bulking agent added, and by the number of mechanical turnings. The bulking
      agents tested in this study were cotton waste, grape stalk, a fresh cow bedding
      and olive leaf; the latter showed the worse performance. Forced ventilation alone
      was revealed to work inadequately in most of the experiments. The composting
      process involved a substantial degradation of the organic substrate with average
      losses of 48.4, 28.6, 53.7 and 57.0% for total organic matter, lignin, cellulose
      and hemicellulose, respectively. Both organic matter biodegradation and
      humification were greatly influenced by the lignocellulosic nature of the
      starting material, which led to low organic matter and nitrogen loss rates and a
      progressive increase in more humified substances, as revealed by the end-values
      of the humification indices. The resulting composts were of good quality in terms
      of nutrient content, stabilised and non-phytotoxic organic matter and low heavy
      metal content. This demonstrates that composting technology can be used as an
      alternative treatment method to turn AL into compost that can be used as organic
      amendments or fertilisers for agricultural systems.

PMID- 18814040
TI  - Are different measures of self-rated health comparable? An assessment in five
      European countries.
AB  - OBJECTIVE: Self-rated health (SRH) is widely used to compare population health
      across countries, but comparability is often hampered by the use of different
      versions of this item. This study compares the WHO recommended version (ranging
      from 'very good' to 'very bad') with the US version (ranging from 'excellent' to
      'poor') in European countries. METHODS: Data came from the Survey of Health,
      Ageing and Retirement in Europe (SHARE). Both the WHO and US versions of SRH were
      measured in representative samples of Europeans aged 50+ (n = 11,643) in five
      countries. Concordance between the two SRH versions and differences in their
      associations with demographics, chronic diseases, functioning and depression were
      assessed using ordered probit regression. RESULTS: The US version has a more
      symmetric distribution and larger variance than the WHO version. Although the WHO
      version discriminates better at the positive end, the US version shows better
      discrimination at the positive end of the scale. Sixty-nine percent of
      respondents provided literally concordant answers, while only about one-third
      provided relatively concordant answers. Overall, however, less than 10% of
      respondents were discordant in either sense. The two versions were strongly
      correlated (polychoric correlation = 0.88), had similar associations with
      demographics and health indicators, and showed a similar pattern of international
      variation. CONCLUSION: Health levels based on different measurements of SRH are
      not directly comparable and require rescaling of items. However, both versions
      represent parallel assessments of the same latent health variable. We did not
      find evidence that the WHO version is preferable to the US version as standard
      measure of SRH in European countries.

PMID- 18814041
TI  - Inhibition of osteolytic bone metastasis by unfractionated heparin.
AB  - In the current study, we examine heparin's anti-metastatic properties by using a
      well-defined mouse model of osteolytic bone metastasis. C57BL/6 mice were treated
      with increasing doses of unfractionated heparin (15, 20, or 25 units/mouse) 30
      min prior to the left ventricular injection of GFP-transfected B16F10 melanoma
      cells. Heparin's effect on tumour burden and bone strength was then quantified 14
      days later by bone histomorphometry and biomechanical testing, respectively.
      Based on histomorphometric analysis of the femurs, injection of GFP-transfected
      melanoma cells resulted in a 37% decrease in cancellous bone volume and a 68%
      increase in osteoclast surface. This was associated with a 13% reduction in bone
      strength as measured by biomechanical testing. However, when the mice were first
      pre-treated with 25 units of heparin, tumour burden was decreased by 73% and
      tumour cell-dependent decreases in both cancellous bone volume and bone strength
      were prevented. Based on these observations, we conclude that heparin inhibits
      the ability of tumour cells to metastasize to bone and that as such, prevents
      tumour cell-induced decreases in bone strength.

PMID- 18814042
TI  - Role of the CXCR4/CXCL12 signaling axis in breast cancer metastasis to the brain.
AB  - Breast cancer is the most common malignancy and second leading cause of cancer
      death in women. Ninety percent of mortality in breast cancer is often associated
      with metastatic progression or relapse in patients. Critical stages in the
      development of aggressive breast cancer include the growth of primary tumors and
      their ability to spread to foreign organs and form metastases, as well as the
      establishment of an independent blood supply within the new tumors. Hence, it is
      imperative to characterize the key molecules that regulate the metastasis of
      human breast cancer cells. The expression of CXCR4/CXCL12 in breast tumors has
      been correlated with a poor prognosis, increased metastasis, resistance to
      conventional therapeutic agents and a poor outcome in the pathogenesis of breast
      cancer. However, effective anti-CXCR4 therapy remains a challenge. Here, we will
      review the putative involvement of the CXCR4/CXCL12 signaling axis in breast
      cancer metastasis to the brain. Characterization of signaling events important
      for breast cancer cell growth and their metastasis to the brain should provide
      insights into breast cancer therapies and improved, successful treatments for
      breast cancer.

PMID- 18814043
TI  - Three-dimensional context regulation of metastasis.
AB  - Tumor progression ensues within a three-dimensional microenvironment that
      consists of cellular and non-cellular components. The extracellular matrix (ECM)
      and hypoxia are two non-cellular components that potently influence metastasis.
      ECM remodeling and collagen cross-linking stiffen the tissue stroma to promote
      transformation, tumor growth, motility and invasion, enhance cancer cell
      survival, enable metastatic dissemination, and facilitate the establishment of
      tumor cells at distant sites. Matrix degradation can additionally promote
      malignant progression and metastasis. Tumor hypoxia is functionally linked to
      altered stromal-epithelial interactions. Hypoxia additionally induces the
      expression of pro-migratory, survival and invasion genes, and up-regulates
      expression of ECM components and modifying enzymes, to enhance tumor progression
      and metastasis. Synergistic interactions between matrix remodeling and tumor
      hypoxia influence common mechanisms that maximize tumor progression and cooperate
      to drive metastasis. Thus, clarifying the molecular pathways by which ECM
      remodeling and tumor hypoxia intersect to promote tumor progression should
      identify novel therapeutic targets.

PMID- 18814044
TI  - Immunohistochemical localization of caspase-3, caspase-9 and Bax in U87
      glioblastoma xenografts.
AB  - Development of new therapies for glioblastoma requires animal models that mimic
      the biological characteristics of human brain tumors. On the other hand,
      potential antitumoral effects of a new therapeutic strategy are often established
      by evaluation of tumor cells apoptosis. Caspases are key mediators in the
      regulation and execution of apoptosis. Caspase-9 is activated during the
      intrinsic pathway downstream of mitochondria while caspase-3 is an effector
      caspase that initiates degradation of the cell in the final stages of apoptosis.
      Bax is a pro-apoptotic member of the Bcl-2 family that play key roles in the
      regulation of intrinsic apoptotic signaling. In the present study we investigated
      the immunohistochemical distribution of caspase 3, 9 and Bax in intracranial U87
      glioblastoma xenograft. Immunohistochemistry showed that the glioblastoma
      xenografts contain cells positive for caspase-3, caspase-9, and Bax.

PMID- 18814045
TI  - Low circulating adiponectin and resistin, but not leptin, levels are associated
      with multiple myeloma risk: a case-control study.
AB  - Accumulating evidence supports a role for obesity in the etiology of multiple
      myeloma (MM). The distinct possibility exists that obesity may be linked to MM
      through altered adipokine secretion and circulating levels, one of which,
      adiponectin, has a protective role in several malignancies, including leukemia.
      In this case-control study, we investigated the role of serum adiponectin,
      resistin, and leptin levels in the etiopathogenesis of MM and we explored their
      association with several established prognostic factors. Seventy three patients
      with incident, histologically confirmed MM and 73 controls matched on gender and
      age were studied between 2001 and 2007, and blood samples were collected. Serum
      adiponectin, leptin, resistin, as well as MM prognostic parameters were
      determined. Statistical analysis of the data was performed using univariate and
      multivariate analyses. Lower serum adiponectin and resistin levels were
      associated with higher risk of MM by bivariate analysis and after adjusting for
      age, gender, BMI, and serum levels of leptin (p < 0.0001). Adiponectin may have a
      protective role in MM, whereas leptin was not associated with risk for MM at a
      comparable level of significance and resistin levels may be decreased via a
      compensatory mechanism. Further studies are needed to confirm these associations
      and to explore the mechanisms underlying adiponectin's role in MM and plasma cell
      dyscrasias.

PMID- 18814046
TI  - Anthropometric characteristics and mammographic parenchymal patterns in post
      menopausal women: a population-based study in Northern Greece.
AB  - OBJECTIVE: To examine the effects of various anthropometric determinants on
      mammographic patterns at postmenopausal ages, accounting for reproductive
      differences. METHODS: Mammograms from 900 post-menopausal women classified into
      high- (P2/DY) versus low-density (N1/P1) groups using the Wolfe criteria were
      associated with changes in body figure, reported and measured height and weight,
      body mass index, hip, waist and chest circumferences, chest/hip ratio, waist/hip
      ratio (WHR), breast size, and leg length. Reproductive factors included ages at
      menarche, first pregnancy and menopause, years since menopause, parity, and
      breast feeding duration. The study was nested within a large cross-sectional
      survey of a population-based breast cancer screening program in Northern Greece.
      RESULTS: Increasing chest circumference (p = 0.002), change in body build during
      adulthood to a heavier profile (p = 0.04), and heavy somatotype at age 18 (p =
      0.007) were the anthropometric determinants significantly associated with low
      density mammographic patterns. CONCLUSIONS: Chest circumference as a measure of
      upper body fat adiposity appears to be a stronger determinant of mammographic
      patterns than body fat distribution (measured as WHR). A heavy body build in
      adulthood is associated with decreased mammographic density. Further studies are
      necessary to confirm our results, ideally prospective cohorts, looking at the
      effect of anthropometric determinants on mammographic pattern changes over time
      and breast cancer risk.

PMID- 18814047
TI  - A functional SNP in the MDM2 promoter, pigmentary phenotypes, and risk of skin
      cancer.
AB  - The MDM2 oncoprotein is a key negative regulator of the tumor suppressor p53. A
      functional MDM2 single nucleotide polymorphism (SNP309) in the promoter region
      increases the affinity of transcription activator Sp1 for the MDM2 gene promoter,
      resulting in higher expression of MDM2 and thus inhibition of p53 transcriptional
      activity. UV-induced p53 activation promotes cutaneous transient pigmentation,
      and the common p53 Arg72Pro polymorphism alters the protein's transcriptional
      activity. We evaluated the effect of MDM2 SNP309 and its interaction with the p53
      Arg72Pro polymorphism on pigmentary phenotypes and skin cancer risk in a nested
      case-control study within the Nurses' Health Study (NHS) among 219 melanoma
      cases, 286 squamous cell carcinoma (SCC) cases, 300 basal cell carcinoma (BCC)
      cases, and 873 controls, and among controls from other studies. We found that the
      G allele of the MDM2 SNP309 was inversely associated with the presence/absence of
      moles on the arm among 3,207 women pooled from controls of three nested case
      control studies within the NHS. Compared with the MDM2 SNP309 T/T genotype,
      adjusted odds ratios (ORs) of having moles on the arms for T/G and G/G genotypes
      were 0.92 (95% confidence interval (CI), 0.78-1.08) and 0.68 (95% CI, 0.53-0.87),
      respectively (p, trend, 0.005). We observed suggestive evidence of the
      association between the carriage of the MDM2 SNP309 G allele and childhood
      tanning tendency (adjusted OR, 1.30; 95% CI, 1.01-1.68). No significant
      associations were found between the MDM2 SNP309 and any of the three types of
      skin cancer. For SCC, the trend of increased risk across the three genotypes of
      MDM2 was stronger among p53 Pro carriers (p, trend, 0.05) than p53 Arg/Arg wild
      type group (p, trend, 0.99; p, interaction, 0.07). These results provide evidence
      for the potential involvement of MDM2 SNP309 in pigmentary traits.

PMID- 18814048
TI  - Tobacco smoking and chewing as risk factors for multiple human papillomavirus
      infections and cervical squamous intraepithelial lesions in two countries (Cote
      d'Ivoire and Finland) with different tobacco exposure.
AB  - Our objective was to compare the association between tobacco smoking and chewing
      and the risk of multiple human papillomavirus (HPV) infections and cervical
      squamous intraepithelial lesions (SILs) in two populations with different tobacco
      exposure. We studied 2,162 women from Cote d'Ivoire, West Africa, and 419 women
      from Finland, Northern Europe, with baseline data on cervical screening, HPV DNA
      status and smoking and chewing habits. The proportion of women who smoked and/or
      chewed tobacco was higher in Finland (36.8%) than in Cote d'Ivoire (3.7%), where
      tobacco chewing (2.6%) was more common than tobacco smoking (1.4%). Having
      multiple HPV infections was common in HPV16 and/or 18-infected women (60.4% in
      Finland and 47.2% in Cote d'Ivoire). There was no increased risk of multiple HPV
      infections among tobacco consumers. We found that women >or=30 years of age
      exposed to tobacco through smoking in Finland (OR: 2.2, 95% CI: 0.5-8.7) and
      chewing in Cote d'Ivoire (OR: 5.5, 95% CI: 2.1-14) had a moderately or highly
      increased risk of high-grade SIL, respectively. In the latter, the risk was
      statistically significant. Our findings emphasize the need for health initiatives
      targeted to prevent tobacco smoking or chewing among women especially in less
      industrialized countries.

PMID- 18814049
TI  - Season of interview and self-report of summer sun protection behaviors.
AB  - Self-report of past behavior may be affected by recall biases that result in over
      or under-reporting. This study explored whether the season an interview was
      conducted affected individuals' self-reported frequency of past summer sun
      protection behaviors, including the use of sunscreen, hats, long sleeves, and
      shade. We examined two existing datasets--National Health Interview Survey (NHIS)
      and the Behavioral Risk Factor Surveillance System (BRFSS) with sample sizes of
      31,428 and 21,122, respectively. Weighted logistic regression models adjusting
      for survey design estimated the influence of interview season on the odds of
      consistent summer sun protection behaviors, while controlling for age, sex, sun
      sensitivity, and geographic region. For NHIS, significant seasonal differences
      were found for all protection behaviors that were measured. For the BRFSS items,
      significant seasonal differences were found only for staying in the shade. Based
      on these findings, when interviewing adults about summer sun safety behavior, we
      recommend conducting the interviews during the summer season or shortly
      thereafter to reduce potential recall biases.

PMID- 18814050
TI  - Proteomic analysis of mammary tissues from healthy cows and clinical mastitic
      cows for identification of disease-related proteins.
AB  - To investigate the disease-related proteins and understand molecular mechanism of
      mastitis at the protein level, this project presents the protein changes in the
      mammary gland between healthy cows and clinical mastitic cows using two
      dimensional gel electrophoresis (2-DE), after stained with colloidal Coomassie
      Bright Blue, six spots of differentially expressed protein were detected by
      PDQuest software and subjected to ion trap mass spectrometer equipped with a HPLC
      system, and five proteins were identified. Hemoglobin beta, kappa-casein and
      tryptophanyl-tRNA-synthetase (TrpRS) in healthy dairy cows, while hemoglobin
      beta, cytochrome C oxidase and annexin V in clinical mastitic cows were
      identified, they were involved in binding, transport and catalytic activity. The
      results may provide valuable information for the investigating of the host
      mammary immune system response to defense against pathogens at the protein level
      and potential protein targets for treatment.

PMID- 18814051
TI  - Age-related difference of site-specific histone modifications in rat liver.
AB  - Aging is associated with decrease in activities of the transcription, replication
      and DNA repair that can result in deterioration of cellular and tissue functions.
      Changes of chromatin structures with age are likely major underling mechanisms
      for the functional decline. Chromatin consists of DNA and histones as well as non
      histone proteins. While age-associated change of DNA methylation is well
      documented, little information is available on site-specific histone
      modifications in aging. We studied here age-related change of selected
      modifications of rat liver histone, i.e., histone H3 Lys9 acetylation (H3K9ac),
      H3 Lys9 methylation (H3K9me), H3 Ser10 phosphorylation (H3S10ph) and H3 Lys14
      acetylation (H3K14ac). H3K9ac was decreased and H3S10ph was increased with age
      significantly. In view of reports indicating that decrease in acetylation and
      increase in phosphorylation of H3 histones can suppress gene activity, our
      findings suggest that a mechanism of decreased chromatin functions with age is
      due to such epigenetic changes.

PMID- 18814052
TI  - Decoupling of the processes of molecular oxygen synthesis and electron transport
      in Ca2+-depleted PSII membranes.
AB  - Extraction of Ca(2+) from the O(2)-evolving complex (OEC) of photosystem II
      (PSII) membranes with 2 M NaCl in the light (PSII(-Ca/NaCl)) results in 90%
      inhibition of the O(2)-evolution reaction. However, electron transfer from the
      donor to acceptor side of PSII, measured as the reduction of the exogenous
      acceptor 2,6-dichlorophenolindophenol (DCIP) under continuous light, is inhibited
      by only 30%. Thus, calcium extraction from the OEC inhibits the synthesis of
      molecular O(2) but not the oxidation of a substrate we term X, the source of
      electrons for DCIP reduction. The presence of electron transfer across PSII(
      Ca/NaCl) membranes was demonstrated using fluorescence induction kinetics, a
      method that does not require an artificial acceptor. The calcium chelator, EGTA
      (5 mM), when added to PSII(-Ca/NaCl) membranes, does not affect the inhibition of
      O(2) evolution by NaCl but does inhibit DCIP reduction up to 92% (the reason why
      electron transport in Ca(2+)-depleted materials has not been noticed before).
      Another chelator, sodium citrate (citrate/low pH method of calcium extraction),
      also inhibits both O(2) evolution and DCIP reduction. The role of all buffer
      components (including bicarbonate and sucrose) as possible sources of electrons
      for PSII(-Ca/NaCl) membranes was investigated, but only the absence of chloride
      anions strongly inhibited the rate of DCIP reduction. Substitution of other
      anions for chloride indicates that Cl(-) serves its well-known role as an OEC
      cofactor, but it is not substrate X. Multiple turnover flash experiments have
      shown a period of four oscillations of the fluorescence yield (both the maximum
      level, F(max), and the fluorescence level measured 50 s after an actinic flash in
      the presence of DCMU) in native PSII membranes, reflecting the normal function of
      the OEC, but the absence of oscillations in PSII(-Ca/NaCl) samples. Thus, PSII(
      Ca/NaCl) samples do not evolve O(2) but do transfer electrons from the donor to
      acceptor sides and exhibit a disrupted S-state cycle. We explain these results as
      follows. In Ca(2+)-depleted PSII membranes, obtained without chelators, the
      oxidation of the OEC stops after the absorption of three quanta of light (from
      the S1 state), which should convert the native OEC to the S4 state. An one
      electron oxidation of the water molecule bound to the Mn cluster then occurs (the
      second substrate water molecule is absent due to the absence of calcium), and the
      OEC returns to the S3 state. The appearance of a sub-cycle within the S-state
      cycle between S3-like and S4-like states supplies electrons (substrate X is
      postulated to be OH(-)), explains the absence of O(2) production, and results in
      the absence of a period of four oscillation of the normal functional parameters,
      such as the fluorescence yield or the EPR signal from S2. Chloride anions
      probably keep the redox potential of the Mn cluster low enough for its oxidation
      by Y(Z)(*).

PMID- 18814054
TI  - Dynamic MR based analysis of tumor movement in upper and mid lobe localized lung
      cancer.
AB  - BACKGROUND AND PURPOSE: Tumor motion is a very important factor in the
      radiotherapy of lung cancer. Uncertainty resulting from tumor movement must be
      considered in 3D therapy planning especially in case of IMRT or stereotactic
      therapy. The aim of our dynamic MR based study was to detect tumor movements in
      upper and mid lobe lung tumors. PATIENT AND METHODS: Twenty-four patients with
      newly diagnosed stage II-IV lung cancer were enrolled into the study. According
      to tumor localization in the right S1-S3 segments 9, in the right S4-S6 segments
      2, in the left S1-S3 segments 9 and in the left S4-S6 segments 4 lesions were
      detected. In normal treatment position individual dynamic MR examinations were
      performed in axial, sagittal and coronal planes (100 slices/30 sec). For tumor
      motion analysis E-RAD PAC's software was used. RESULTS: Movements of the tumor
      under normal breathing conditions were registered in the three main directions.
      The mean antero-posterior deviation was 0,109 cm (range: 0,063 cm-0,204 cm), the
      mean medio-lateral deviation was 0,114 cm (range: 0,06 cm- 0,244 cm). The
      greatest deviation was measured in cranio-caudal direction (mean: 0,27 cm, range:
      0,079 cm- 0,815 cm). The mean direction independent deviation was 0,18 cm (range:
      0,09 cm- 0,48 cm). CONCLUSION: Dynamic MR is a sensitive and well tolerated
      method for tumor motion monitoring in high precision 3D therapy planning of lung
      cancer patients. Our results demonstrate that tumors located in the upper and mid
      lobes have moderate breath synchronous movements. The greatest deviation occur in
      cranio-caudal direction.

PMID- 18814053
TI  - Candida albicans VPS4 is required for secretion of aspartyl proteases and in vivo
      virulence.
AB  - Candida albicans secretes aspartyl proteases (Saps) during infection. Although
      Saps are secretory proteins, little is known about the intracellular trafficking
      and secretion of these proteins. We previously cloned and analyzed the C.
      albicans pre-vacuolar protein sorting gene VPS4, and demonstrated that
      extracellular Sap2p is absent in the culture supernatants of the vps4delta null
      mutant. We therefore investigated the role of the C. albicans pre-vacuolar
      secretion pathway in the trafficking of Sap4-6p and in vivo virulence. The C.
      albicans vps4delta mutant failed to produce extracellular Sap4-6p. Next, when
      tested in a mouse model of disseminated candidiasis, the vps4delta mutant was
      greatly attenuated in virulence. Histopathological analysis indicated that
      infection with the vps4delta mutant did not cause renal microabscess formation,
      in contrast to the wild-type strain. Our results imply that VPS4 is required for
      extracellular secretion of Sap4-6p, and that C. albicans requires an intact pre
      vacuolar secretory pathway for wild-type virulence in vivo.

PMID- 18814055
TI  - [Results of a prospective multicenter trial for treatment of acromioclavicular
      dislocation].
AB  - OBJECTIVE AND METHODS: The treatment of the acromioclavicular joint dislocation
      is a topic of constant debate. Objective of the study was to analyze if operative
      treatment of Rockwood types 3 and 5 acromioclavicular joint dislocations is
      superior to nonoperative treatment. Treatment outcomes of 100 patients (91 male,
      9 female, median age 33.7 +/- 8.6) from 4 different hospitals/departments of
      trauma surgery were analyzed. Clinicofunctional, radiological, as well as
      subjective parameters were taken into consideration. RESULTS: Clinicofunctional
      outcome of the operative treatment of acromioclavicular joint dislocation was
      very good in 91.2 % of patients. 87.7 % of the operated patients had a
      subjectively stable joint. The patients operated on for the acromioclavicular
      joint dislocation were capable of exercising after 13 weeks post surgery. versus
      25.3 weeks in nonoperatively treated patients. The operated patients had a Rowe
      score and Constant score as high as 90.7 and 91.8 respectively, reflecting an
      excellent treatment outcome. CONCLUSION: Operative anatomic reconstruction of the
      injured acromioclavicular joint leads to very good clinicofunctional outcomes.
      The operative technique plays only a minor role in achieving these outcomes. The
      rate of complications is low for all operative techniques listed here. Demanding
      patients and multimedia education of patients are the reasons for a majority of
      operated patients in this study (97 %).

PMID- 18814056
TI  - [Shoulder injuries in overhead athletes: utility of MR arthrography].
AB  - INTRODUCTION: The goal of this work was to assess the accuracy of the MR
      Arthrografie in the evaluation of over head athletes injuries in comparison with
      athroscopy. MATERIAL AND METHODS: In 29 patients (middle age: 30 years, 21 male,
      8 female, age 16 - 53 years) with persistent pain after conservative therapy an
      Arthro-MRI with intraarticular application of gadolinum was performed prior to
      arthroscopic surgery. The MRI was retrospectivly analysed of three examiners
      independently from one another. The result were compared to the results of the
      Arthroscopy. Interrater Reliability was calculated by using of Cohens Kappa.
      RESULTS: The MR-Arthrography could demonstrate 8 of 9 (88.9 %) partial tears of
      he rotator cuff. All SLAP (Superiores Labrum from Anterior to Posterior) Lesions
      as well as all bankart type Lesions were recognized through the MR-Arthrography.
      However, dependent upon the experience of the examiner in a span between 33.3 %
      (fellow radiologist) and 93.3 % (consultant radiologist). We found a high
      agreement between consultant radiologist and shoulder surgeon with Kappa of 0.79
      for rotator cuff tear-, 0.86 for Bankart- and 0.82 for SLAP-Lasionen.

PMID- 18814057
TI  - [Winter sports and shoulder arthroplasty].
AB  - Nowadays, a general negative evaluation of sportive activity regarding different
      kinds of sport following arthroplasty is at present no more scientifically
      supported. However, at present no valid guidelines regarding sportive activity of
      patients after implantation of shoulder joint arthroplasty exist. The question
      regarding the ability of performing winter sports activities of patients treated
      with shoulder joint endoprothesis has not been answered so far. Therefore the aim
      of the presented work was to identify winter sports-specific risks for patients
      treated with shoulder joint endoprothesis as well as to critically discuss the
      actual literature in refer to winter sport activities. Criteria for the education
      of patients with shoulder joint endoprothesis as well as consultation regarding
      winter sport activities will be provided for the orthopaedic surgeon.

PMID- 18814058
TI  - [Hip injuries in professional and amateur soccer goalkeepers].
AB  - Soccer goalkeeper often dive to the side loading their hip. Different hip
      injuries might result. Within the scope of this study the hip injury rate of
      professional and amateur soccer goalkeepers was investigated. Most often players
      suffer from contusions and abrasions. Bursitis is reported from professional
      players, but hardly from amateur players. Generally amateur players are injured
      more often than professional players. For all players the injury risk during
      exercise is significantly higher than during a match. The exercise frequency
      showed a weak link to incidence rate only. For age, gender and exercise intensity
      no influence of the injury rate was found. Artificial playground resulted in a
      higher injury rate than natural grass, although the difference was not
      statistically significant. It was noted that team coachs and players indicated a
      different perception of the injury rate. The use of protective sports wear (hip
      protectors) did not significantly influence the injury rate.

PMID- 18814059
TI  - [Effects of soccer-specific strains on the locomotor system].
AB  - PROBLEMS: Soccer as a Stop-and-Go-sport goes along with a high level of physical
      strain on the locomotor system. Compared to similar kinds of sports, soccer is
      characterized by a high prevalence of overloads/injuries in the pelvic region.
      Since soccer frequently involves one-sided shot-training, modifications in the
      pelvic statics are possible. METHODS: In a pilot study including 15 football
      players-FP (age 26.9 +/- 3.1 yrs; 4.4 +/- 0.4 training units/week+ 1 leaque game)
      the pelvic statics was measured using the 3-d-recording system CMS70 (Zebris,
      Germany) directly before and after a defined shot training. The positions of the
      right and the left posterior superior iliac spines - PSIS were compared.
      Additionally, the stiffness of selective muscles was analyzed. RESULTS: Before
      intervention the right PSIS was heightened in 8 FP. In 4 FP the pelvic statics
      was balanced and in 3 FP the right PSIS was abased. After the shot training, the
      pelvic statics was balanced in 4 FP. In contrast, 10 FP showed a higher right
      PSIS and 1 FP had a lower right PSIS. However, modifications of the pelvic
      statics were detected in all directions. DISCUSSION: Our study demonstrates
      modification of the pelvic statics by asymmetric soccer-specific strains, but the
      reactions were individually different. It is possible, that changes in the pelvic
      statics may lead to changed function or overstrain of advertising muscles.

PMID- 18814060
TI  - [Damping inserts have no load reducing effect in the fatigued state].
AB  - Overload injuries to the lower limbs may be attributed to repetitive, non
      physiological load stimuli. However, these impact loads acting on the
      musculoskeletal can be reduced by wearing damping inserts. To date, however,
      there is only little evidence as to whether this positive effect can be assigned
      to the damping insert and, furthermore, whether this effect is detectable in
      states of muscle fatigue. Therefore, the influence of muscle fatigue in
      combination with the wearing of damping inserts was investigated in 13 subjects.
      The parameters examined in this study were ground reaction forces during walking
      and the muscular activation profile of the lower limb in the phase of initial
      ground contact. The results showed that neither in comparisons with and without
      damping inserts nor in states of muscular fatigue could significant differences
      were found in the ground reaction forces. Wereas, no significant differences
      could be detected in the investigated muscles, with and without damping inserts,
      preactivation in the peroneal and biceps femoris muscles were significantly
      earlier, in states of muscular fatigue with damping inserts, while no changes
      could be found in the anterior tibial, soleus, vastus lateralis and gastrocnemius
      muscles. The present results demonstrate that wearing damping inserts does not
      lead to a positive effect with regard to a reduction of the ground reaction
      forces. The earlier preactivation in the case of muscle fatigue with a damping
      insert is indicative of an increased energy expenditure which may be possibly
      associated with increased knee and ankle joint control. The high satisfaction
      concerning the comfort of wearing such inserts revealed by a questionnaire did
      not correlate with a reduction in loading condition. On the basis of the present
      results we cannot recommend the wearing of damping soft sole inserts in the
      context of a reduction in load condition.

PMID- 18814063
TI  - Antiphospholipid antibodies and the antiphospholipid syndrome II: limitations,
      standardization, and clinical utility of laboratory testing.

PMID- 18814064
TI  - A quarter of a century in anticardiolipin antibody testing and attempted
      standardization has led us to here, which is?
AB  - The anticardiolipin (aCL) test has been widely used by physicians since the mid
      1980s for diagnosing patients with antiphospholipid syndrome (APS). Establishment
      of this diagnosis has enabled effective management of patients with recurrent
      thrombosis and recurrent pregnancy losses. The test was first established in 1983
      as a radioimmunoassay and soon thereafter converted into an enzyme-linked
      immunosorbent assay (ELISA). The other test commonly used in the diagnosis of APS
      is the lupus anticoagulant (LA) test. The aCL ELISA is sensitive for the
      diagnosis of APS but lacks specificity. On the other hand, the LA assay, although
      more specific, is not as sensitive as the aCL ELISA. More specific tests are now
      available such as the anti-beta2 glycoprotein I (anti-beta2GPI) assay, the
      antiprothrombin assay, and other ELISAs that use negatively charged phospholipids
      instead of cardiolipin to coat the plates. In the past 25 years, there have been
      numerous efforts to standardize aCL, LA, and anti-beta2GPI tests but there are
      still reports of significant intra- and interlaboratory variation in results for
      all three assays. This article discusses in detail the clinical value of these
      tests, technical problems associated with their use, the current laboratory
      classification criteria for diagnosis of APS, and possible new and better assays
      that will be available in the near future for diagnosis of APS.

PMID- 18814065
TI  - Clinical utility of laboratory tests used to identify antiphospholipid antibodies
      and to diagnose the antiphospholipid syndrome.
AB  - The antiphospholipid syndrome (APS) is defined by thrombotic and/or obstetric
      events together with the presence of antiphospholipid antibodies in plasma of
      patients. The original laboratory criteria of APS included lupus anticoagulants
      (LA) and/or IgG/IgM anticardiolipin antibodies (aCL). They were recently updated
      with the addition of IgG/IgM anti-beta2 glycoprotein I antibodies (anti
      beta2GPI), a better definition of "medium to high antibody titer," and the
      extension to 12 weeks of the "persistence in time." The revised criteria
      represent an improvement; however, the potential overdiagnosis of APS remains
      possible, thus putting patients at risk of overtreatment. To reduce this
      possibility, proposals have been made to implement strict guidelines for the
      performance of the LA assay, to exclude aCL measurements in their current
      application from the criteria, and to limit the measurement of anti-beta2GPI to
      the G isotype. This should also help in simplifying the laboratory workup of
      patients being investigated for APS.

PMID- 18814066
TI  - Antiprothrombin antibody testing: detection and clinical utility.
AB  - Anticardiolipin antibody (aCL), anti-beta2 glycoprotein I antibodies, and lupus
      anticoagulant (LA) are the only laboratory tests considered within the revised
      criteria for the classification of the antiphospholipid syndrome (APS). Recently,
      antibodies against phosphatidylserine-prothrombin complex (aPS/PT) have been
      detected, and these antibodies, rather than antibodies against prothrombin alone,
      are closely associated with APS and LA. The sensitivity and specificity of aPS/PT
      for the diagnosis of APS were assessed in a population of patients with a variety
      of autoimmune disorders. aCL and aPS/PT have similar diagnostic value for APS,
      therefore aPS/PT should be further explored, not only for research purposes but
      also as a candidate for one of the laboratory criteria for the classification of
      the APS.

PMID- 18814067
TI  - Technical aspects in laboratory testing for antiphospholipid antibodies: is
      standardization an impossible dream?
AB  - Anticardiolipin (aCL) and anti-beta2 glycoprotein I (anti-beta2GPI) assays are
      widely performed because they are part of the laboratory criteria for the
      antiphospholipid syndrome (APS). Despite several standardization workshops and
      the availability of a worldwide accepted calibrator material for aCL, a high
      variability in numerical assay results and in sample classification is still
      observed in comparative studies and external quality control surveys. For anti
      beta2GPI assays, comparison of numerical values is impeded by the absence of a
      common calibrator material, and external quality surveys similarly show a large
      overlap in sample classification. Numerous variables impact assay results, among
      them the source and integrity of beta2GPI, the secondary calibration process, and
      the assessment and derivation of cutoff values. For both assays, the vast
      majority of laboratories use commercial kits whose number has risen considerably
      in the past years. However, many problems persist, and there is a need to improve
      the comparability in assay results. The use of monoclonal antibodies as reference
      calibrators has to be especially considered, with their suitability evaluated by
      future collaborative studies and external quality controls surveys. Manufacturers
      should provide more precise information on results obtained when testing control
      groups for establishing reference ranges and cutoff values. From the customers'
      perspective, it is important that each laboratory, even if using commercial kits,
      assesses its local cutoff value whenever possible. In the field of autoimmunity,
      assay standardization is a difficult but nevertheless important task. Much more
      effort is needed to reduce the high interlaboratory variability in assay results
      even if absolute standardization cannot be feasibly achieved.

PMID- 18814068
TI  - Twenty-two years of failure to set up undisputed assays to detect patients with
      the antiphospholipid syndrome.
AB  - The antiphospholipid syndrome is defined by the persistent presence of
      antiphospholipid antibodies in plasma of patients with a history of thrombosis
      and/or pregnancy morbidity. From the definition in 1985 onwards, confusion has
      arisen concerning who has the syndrome and who has not. Although the clinical
      criteria are well defined, there is ongoing discussion regarding serologic
      criteria. Lack of standardization of the assays that define the serologic
      criteria, notably phospholipids-dependent coagulation assays, and enzyme-linked
      immunosorbent assays (ELISAs) for anticardiolipin and anti-beta2 glycoprotein I,
      have led to heated arguments regarding which population(s) of antibodies should
      be measured to detect a patient at risk for (recurrent) thrombosis or pregnancy
      complications. Everybody agrees on the need to better standardize the assays, but
      different views are held on how this should be achieved, and commercial interests
      have hampered consensus on which assays should be applied, how they should be
      performed, and the cutoff values that discriminate between pathologic and
      nonpathologic results. New prospective cohort studies to reevaluate the clinical
      significance of the available assays are essential, but the lack of sufficient
      patient numbers visiting single hospital facilities frustrates progress. This
      review discusses shortcomings of the current serologic assays, provides
      strategies to solve these shortcomings, and discusses new developments/assays to
      improve the specificity of such assays for thrombosis and pregnancy
      complications.

PMID- 18814069
TI  - Are the current attempts at standardization of antiphospholipid antibodies still
      useful? Emerging technologies signal a shift in direction.
AB  - The pathogenic role of antiphospholipid antibodies (aPL) has been widely
      established over past years in several experimental models and clinical studies.
      Accordingly, the detection of aPL by immunoassays (anticardiolipin antibodies;
      anti-beta2 glycoprotein I antibodies) has become a routine practice in the
      clinical workup of patients with systemic autoimmune diseases. aPL are mostly
      assayed using commercial ELISA kits, whose performance has not been found to be
      sufficiently concordant among the different manufacturers. In the past years,
      collaborative groups have spent considerable effort to reach some form of
      standardization but this process is still ongoing. Such lack of standardization
      has recently become even more crucial, as manufacturers have had to face an
      increasing demand for fully automated tests for aPL, like those test systems that
      have been developed for other autoantibodies (e.g., antinuclear antibodies, anti
      ENA antibodies). We therefore report our recent experience with two newly
      developed automated methods for anticardiolipin antibodies testing. In
      particular, we discuss the results obtained using routine samples, as we believe
      that these better reflect the "real-life" situation in which those automated
      methods will operate. We also mention other emerging technologies in the field of
      aPL detection.

PMID- 18814070
TI  - A consensus approach to the formulation of guidelines for laboratory testing and
      reporting of antiphospholipid antibody assays.
AB  - Despite numerous past and ongoing efforts, there remains significant variation in
      results from assays for the major antiphospholipid antibodies (aPL), namely
      anticardiolipin (aCL), anti-beta2 glycoprotein I (anti-beta2GPI), and lupus
      anticoagulant (LA). There is therefore a need to produce comprehensive guidelines
      on laboratory testing and reporting of aPL assays. However, because of the
      paucity of good-quality published evidence, there is a heavy reliance on expert
      opinion, and thus the existing consensus guidelines for aPL testing and reporting
      are largely eminence based rather than evidence based. This may potentially bias
      recommendations to reflect the personal preferences of those who have the
      greatest influence during the guideline formulation process. This article largely
      details the experience of the Australasian Anticardiolipin Working Party in
      undertaking a consensus approach to formulation of guidelines on aCL and anti
      beta2GPI testing and reporting, including measures taken to minimize these
      issues. Despite the time-consuming nature of the process, given the paucity of
      good-quality published evidence, formulation of guidelines by the consensus
      process remains an important initiative to improve the standardization of aPL
      testing and reporting.

PMID- 18814071
TI  - Laboratory testing for lupus anticoagulants: diagnostic criteria and use of
      screening, mixing, and confirmatory studies.
AB  - The presence of lupus anticoagulants (LA) in plasma is a strong risk factor for
      thromboembolism and fetal loss. Because of this, demand for testing for LA is
      increasing, but the performance of clinical laboratories in terms of its
      detection is still a matter of concern. This is due in part to the lack of
      specific tests but also to the lack of standardization and application of the
      diagnostic criteria. The aim of this article is to review the diagnostic criteria
      and the many issues that may affect test results.

PMID- 18814072
TI  - Laboratory testing for lupus anticoagulants: pre-examination variables, mixing
      studies, and diagnostic criteria.
AB  - The latest international guidelines for the laboratory diagnosis of lupus
      anticoagulants (LA) date back to 1995 and are in need of revision. Various
      patterns of practice and interpretation by clinical laboratories have altered the
      intent or usage of the criteria and recommendations made at that time. Moreover,
      various topics in the preexamination phase of LA testing (such as the role of the
      clinician in test ordering, the impact of direct thrombin inhibitors or oral
      anticoagulant therapy, and patient biologic variation) need to be considered in
      future guidelines. In like fashion, examination issues relating to mixing studies
      will need critical review. Mixing studies have been applied to a variety of low
      phospholipid LA screening assays, and no uniformity or standardization exists as
      to how these test results should be interpreted or if in fact they are suitable
      for identifying weak lupus anticoagulants.

PMID- 18814073
TI  - Laboratory testing and identification of antiphospholipid antibodies and the
      antiphospholipid syndrome: a potpourri of problems, a compilation of possible
      solutions.
AB  - The antiphospholipid syndrome (APS) is an autoimmune condition characterized by
      vascular thromboses and/or pregnancy morbidity, and its diagnosis currently
      requires laboratory evidence of the presence of antiphospholipid antibodies
      (aPL). aPL are in turn identified using a large number of laboratory procedures
      based on one of two distinct test processes, namely solid-phase assays and liquid
      phase assays. The former includes anticardiolipin antibodies and anti-beta2
      glycoprotein I antibodies, and the latter are centered on clot-based tests that
      are used to identify the so-called lupus anticoagulant. The current article
      provides an overview of the laboratory testing and identification of aPL, and in
      particular the limitations, standardization, and clinical utility of such
      testing. We also review preanalytical, analytical, and postanalytical issues that
      compromise the clinical utility of these tests. Finally, we provide a list of
      recommendations aimed to foster broader international cooperation to assist in
      the preparation of integrated guidelines, for both solid-phase and liquid-phase
      assays, and for laboratory testing, clinical ordering, and interpretation.

PMID- 18814076
TI  - Vascular diseases of the liver.

PMID- 18814077
TI  - Ischemic cholangiopathy.
AB  - Bile ducts are supplied with blood exclusively via hepatic arteries. Obstruction
      of large arteries is rapidly compensated for by the opening of preexisting
      intrahepatic or transcapsular collateral arteries, which prevents ischemic
      damage. Ischemic bile duct injury may occur when small hepatic arteries or the
      peribiliary vascular plexus are injured, or when all possible arterial blood
      supplies are interrupted, as is the case in transplanted liver with hepatic
      artery thrombosis. Most causes of bile duct ischemia are iatrogenic. Systemic
      diseases involving small hepatic arteries may also be implicated. Depending on
      the extent and velocity of the arterial obstructive process, ischemic
      cholangiopathy may present as acute formation of biliary casts, bile duct
      necrosis, or chronic disease resembling primary sclerosing cholangitis. In many
      patients, correction of arterial obstruction is not possible. When biliary
      drainage or reconstruction is not possible or has failed, liver transplantation
      is the only means of providing potential cure.

PMID- 18814078
TI  - Hepatic vascular malformations in hereditary hemorrhagic telangiectasia.
AB  - Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant vascular
      disorder that can involve the liver diffusely in the form of vascular
      malformations ranging from small telangiectases to discrete arteriovenous
      malformations. Anatomically, three different patterns of abnormal vascular
      communications can occur in liver: portal vein to hepatic vein (portovenous),
      hepatic artery to hepatic vein (arteriovenous) and hepatic artery to portal vein
      (arterioportal), with the most common being arteriovenous. Only 5 to 8% of
      patients with these vascular malformations are symptomatic. When symptomatic,
      patients present with high-output cardiac failure, biliary ischemia (which, when
      severe, can progress to biliary and hepatic necrosis and lead to acute liver
      failure), or portal hypertension. Other less common presentations include
      portosystemic encephalopathy and abdominal angina. Diagnosis is confirmed by
      Doppler ultrasonography or multidetector computed tomography. The hallmark
      findings are intrahepatic hypervascularization and an enlarged common hepatic
      artery. Focal nodular hyperplasia and nodular regenerative hyperplasia are common
      findings. Symptomatic patients are treated with intensive medical treatment aimed
      at the predominant clinical presentation. Patients who fail aggressive medical
      therapy and those with acute biliary/hepatic necrosis should be considered for
      liver transplantation.

PMID- 18814079
TI  - Budd-Chiari syndrome.
AB  - Primary Budd-Chiari syndrome is related to thrombosis of hepatic veins or the
      terminal portion of the inferior vena cava. This rare disease is usually caused
      by multiple concurrent factors, including acquired and inherited thrombophilias.
      Half of the patients with primary Budd-Chiari syndrome are affected with a
      myeloproliferative disease, the recognition of which is largely based on the
      assessment of V617F Janus tyrosine kinase 2 (JAK2) mutation in peripheral
      granulocytes. A diagnosis of Budd-Chiari syndrome should be considered in any
      patient presenting with acute or chronic liver disease, as clinical
      manifestations are extremely diverse. Spontaneous outcome in symptomatic patients
      is poor. Diagnosis can be made in most patients noninvasively when imaging shows
      venous obstruction and/or collaterals. A treatment strategy is recommended where
      anticoagulation is given first, followed by angioplasty when appropriate, then
      TIPS in patients not responding to previous measure, and finally liver
      transplantation. This strategy has achieved 5-year survival rates close to 90%.

PMID- 18814080
TI  - Intrahepatic portal venopathy and related disorders of the liver.
AB  - Intrahepatic portal venopathy leads to various entities that are important causes
      of portal hypertension. Noncirrhotic portal fibrosis (NCPF) occurs in the Indian
      subcontinent, whereas idiopathic portal hypertension (IPH) occurs in Japan
      although the pathogenesis and presentation of both are similar. NCPF presents
      mainly with upper gastrointestinal bleeding; IPH presents with massive
      splenomegaly. The liver functions are preserved. Wedged hepatic venous pressure
      is normal, but portal venous pressure is high indicating a presinusoidal block.
      Patients are best managed with endoscopic therapy or surgery, with better results
      than in patients with cirrhosis. Nodular regenerative hyperplasia is a
      histological diagnosis characterized by development of nodules in the liver due
      to uneven perfusion of the portal venous blood. These patients may develop portal
      hypertension and if they bleed would require treatment as in NCPF/IPH.
      Schistosomiasis produces portal hypertension by the development of fibrous tissue
      around the portal veins as a response to schistosome eggs. Gratifying results
      have been reported with praziquantel therapy. Rarely sarcoidosis and chronic
      biliary obstruction may also produce portal venopathy.

PMID- 18814081
TI  - Extrahepatic portal vein thrombosis.
AB  - Noncirrhotic, nontumoral portal vein thrombosis (PVT) is the second most-frequent
      cause of portal hypertension in the world. General thrombophilic factors can be
      identified in approximately 60% of patients. PVT may manifest as an acute
      process. However, the acute episode more frequently is asymptomatic or
      paucisymptomatic and portal vein thrombosis is misdiagnosed until the development
      of complications secondary to portal hypertension, such as variceal bleeding or
      portal biliopathy. Although no randomized controlled trials have been performed,
      after the diagnosis of acute PVT early initiation of anticoagulation (within 30
      days of the onset of symptoms) is recommended to achieve recanalization. In
      patients with portal cavernoma, anticoagulation is aimed to prevent the
      progression and recurrence of thrombosis. Because of the lack of data in this
      specific population, variceal bleeding is managed as in cirrhotic patients.
      Ursodeoxycholic acid has been proposed empirically for the treatment of patients
      with symptomatic portal biliopathy. Choledocholithiasis might be present,
      complicating a bile duct stenosis. Accordingly, an endoscopic retrograde
      cholangiopancreatography with sphincterotomy, extraction with balloon catheter,
      and stent placement is indicated. Mortality among patients with PVT is low (5
      year mortality rate of 5 to 10%) and is mainly related to associated diseases
      rather than to complications of portal hypertension.

PMID- 18814082
TI  - The role of thrombophilia in splanchnic vein thrombosis.
AB  - In the last few years, the mechanistic role of thrombophilia due to
      hypercoagulability and of clonal disorders of hemopoiesis such as chromosome
      Philadelphia-negative chronic myeloproliferative disorders has been increasingly
      recognized in primary splanchnic vein thrombosis. As in deep venous thrombosis of
      the lower limbs, the frequent finding of several prothrombotic disorders in the
      same individual has led to the concept of primary splanchnic vein thrombosis as a
      multifactorial disease. Significant progress has been made in determining the
      molecular bases of inherited thrombophilia, and particularly in the
      identification of molecular markers of clonal disease in the so-called occult or
      latent myeloproliferative disorders. In this review article, the authors discuss
      the current knowledge on the role of thrombophilia in extrahepatic portal vein
      obstruction and in the Budd-Chiari syndrome, two of the most clinically relevant
      splanchnic vein thromboses.

PMID- 18814083
TI  - Benign and malignant vascular tumors of the liver in adults.
AB  - Vascular tumors of the liver in adult patients include cavernous hemangioma, a
      common benign tumor; epithelioid hemangioendothelioma, a rare, usually low-grade
      malignant tumor; and angiosarcoma, a rare and very aggressive tumor. All these
      primary mesenchymal tumors develop on a normal liver and may also affect other
      organs. Their pathogenesis remains largely unknown. Hepatic tumors are
      increasingly detected incidentally due to widespread use of modern abdominal
      imaging techniques. Therefore, reliable noninvasive characterization and
      differentiation of such liver tumors is of major importance for clinical
      practice. Hemangioma follows a benign course, and a nonoperative approach for the
      majority of these lesions is recommended. A definitive diagnosis of epithelioid
      hemangioendothelioma and angiosarcoma requires histopathologic examination. Liver
      transplantation at an early stage has greatly improved the prognosis of
      epithelioid hemangioendothelioma. The prognosis of angiosarcoma remains dismal.
      Designing a worldwide database that contains all data about patients with these
      rare diseases is recommended.

PMID- 18814084
TI  - Hepatic vascular involvement related to pregnancy, oral contraceptives, and
      estrogen replacement therapy.
AB  - Both pregnancy and oral contraception (mainly when estrogen is included) may
      precipitate the development of Budd-Chiari syndrome in patients with underlying
      thrombophilia. By contrast, there is little evidence for such a role of pregnancy
      and oral contraception in women with portal vein thrombosis. In pregnant women,
      special modalities for anticoagulation are required, whereas the management of
      portal hypertension can be similar to that recommended in other diseases and
      settings. Hereditary hemorrhagic telangiectasia may deteriorate during pregnancy
      and improve after delivery. Hepatic sinusoidal dilatation and hepatic peliosis
      are classic complications of long-term use of oral contraceptives. The impact of
      pregnancy or oral contraceptives on the natural history on hemangioma and focal
      nodular hyperplasia appears to be limited. Preeclampsia, a liver disease unique
      to pregnancy, may be complicated by life-threatening liver vascular involvement,
      especially when the syndrome of hemolysis, elevated liver enzymes, and low
      platelet count (HELLP syndrome) is present.

PMID- 18814085
TI  - A 56-year-old man with sudden onset of portosystemic encephalopathy years after
      severe electrocution trauma.
AB  - A 56-year-old white male painter, with a history of major electrocution and deep
      thermal injury, developed mental status changes initially ascribed to an acute
      neurological event. Unexpectedly, magnetic resonance imaging (MRI) of the head
      showed areas of high signal intensity in the basal ganglia, which can be observed
      in advanced liver disease. An electroencephalogram (EEG) suggested metabolic
      encephalopathy and coexistent elevation of ammonia, indicative of significant
      liver disease. The patient had had a long history of right upper quadrant pain
      and fluctuation in liver tests following the electrocution trauma. For these
      symptoms, he underwent surgery 7 years prior to his current presentation of
      portosystemic encephalopathy, and was found to have a gangrenous acalculous
      cholecystitis. Intraoperative cholangiogram suggested possible strictures within
      the right hepatic ducts. Multiple liver biopsies, however, showed only steatosis.
      Current evaluation including liver biopsy, MRI, magnetic resonance angiography
      (MRA), and magnetic resonance cholangiopancreatography (MRCP), revealed
      progression to biliary cirrhosis with large bile duct obstruction, and hepatic
      artery thrombosis/occlusion with evidence of left lobe atrophy and right lobe
      compensatory hypertrophy. The pathobiology of ischemic bile duct injury is
      discussed herein. The case is an example of serious late sequelae of an
      occupational injury.

PMID- 18814086
TI  - [World Conference 2008 in Dana Point: important developments in the field of
      pulmonary hypertension].

PMID- 18814087
TI  - [Novel concepts in the pathobiology of pulmonary arterial hypertension].
AB  - Pulmonary arterial hypertension (PAH) is a devastating disease that is
      characterized by a high mortality. The pathogenesis of PAH is multifactorial. In
      addition to hereditary factors (e. g., BMPR2 mutations), numerous environmental
      factors may trigger the onset and progression of the disease. An imbalance
      between vasoconstrictive and vasodilative factors leads to vasoconstriction in
      the pulmonary circuit, resulting in an increase of pulmonary vascular resistance
      and pulmonary artery pressure. Alterations of several signaling pathways (i. e.;
      endothelin, nitric oxide and prostacyclin pathways) contribute to an increase of
      pulmonary vascular tone, and these pathways represent the targets of the current
      therapeutic interventions. However, PAH is increasingly recognized as a chronic
      proliferative disease particularly of the small pulmonary arteries, that is
      primarily characterized by morphological changes of the vascular wall ("vascular
      remodeling"). These changes are particularly induced by peptide growth factors
      such as platelet-derived growth factor (PDGF) that elicit their signals via
      activation of membrane-bound receptor tyrosine kinases (RTK). Accordingly, there
      is both experimental and clinical evidence for a therapeutic efficacy of tyrosine
      kinase inhibitors (TKI), which provide the basis for "reverse remodeling"
      strategies and indeed represent a promising novel approach for the treatment of
      PAH. Epidermal growth factor (EGF), soluble guanylate cyclase (sGC), and
      phosphodiesterase type 1 (PDE1) may represent additional future target molecules.
      PAH leads to progressive right heart failure which determines the outcome of PAH
      patients. The pathomechanisms of right heart failure should therefore also be
      considered for the development of novel therapeutic concepts.

PMID- 18814088
TI  - [Update in basic research in the therapy of pulmonary arterial hypertension].
AB  - Pulmonary hypertension is a vasculoproliferative disorder which is characterized
      by vasoconstriction and proliferation of vascular cells within the vessel wall.
      Mostly addressing the increased vascular tone, prostacyclin and its analogues,
      endothelin-receptor antagonists and phosphodiesterase type 5 inhibitors have been
      approved for treatment of PAH and represent the current therapeutic options.
      Currently, research focuses on the development of causal treatment regimens
      aiming a normalization of the vessel structure. Mechanistically, increased
      proliferation, migration and a resistance to apoptosis of vascular cells
      represent key events in disease progression. In clinical relevant animal models
      of pulmonary hypertension, new non-vasoactive drugs could not only attenuate
      ("Anti-Remodeling") but reverse ("Reverse-Remodeling") the disease. These
      compound classes include tyrosine kinase inhibitors, elastase inhibitors, and
      phosphodiesterase inhibitors. For some of these agents clinical trials are
      already initiated which will address safety and efficacy. In addition, there is
      further development of new vasodilators addressing well known and new signaling
      pathways. Taken together, there is advanced research in the field of pulmonary
      vascular diseases and the efficacy of several new drugs is currently addressed in
      clinical trials.

PMID- 18814089
TI  - [Echocardiography and magnetic resonance imaging in patients suffering from
      pulmonary arterial hypertension].
AB  - The therapeutic options for pulmonary arterial hypertension (PAH) have
      significantly improved in the last few years. But the disease is still too often
      diagnosed late in its course. In more than 80% of patients the diagnosis is made
      and treatment started when the condition is already in NYHA class III-IV with a
      very poor prognosis. According to the EARLY study, beginning treatment 3 - 6
      months earlier can improve prognosis and progression of the PHT. Late diagnosis
      is first of all due to the fact that it is asymptomatic in the early stages, such
      symptoms as dyspnoea, peripheral edema or syncope frequently occurring only when
      there are already signs of heart failure. Secondly, there is as yet no method for
      the early diagnosis of PHT. But echocardiography and magnetic resonance imaging
      (MRI) are non-invasive modes that are important for screening and follow-up.
      Among noninvasive methods echocardiography shows the greatest diagnostic
      sensitivity and specificity. It should be undertaken in all patients in whom
      pulmonary hypertension (PHT) is suspected. But because of the particular geometry
      of the right ventricle its examination is difficult. New diagnostic techniques
      allow for assessment of additional information of right ventricular function.
      Right heart catheterization is essential for further elucidating PHT.

PMID- 18814090
TI  - [The role of cardiopulmonary exercise testing in the assessment of pulmonary
      hypertension].
AB  - Cardiopulmonary exercise testing (CPET) is an important diagnostic instrument for
      early detection, differential diagnosis and follow-up evaluation in pulmonary
      hypertension (PH). A pulmonary vasculopathy as the underlying cause for pulmonary
      arterial hypertension (PAH) can be detected in early stages by measuring gas
      exchange during exercise. There are characteristic patterns which are typically
      seen in patients with PAH. Regarding follow-up assessments, CPET can quantify
      cardiopulmonary exercise capacity in a more differentiated way than global
      exercise tests like the 6-minute walking distance. Different pathophysiological
      mechanisms accounting for pulmonary hypertension can be separately evaluated by
      CPET. Although tremendous progress has been made regarding sensor technology and
      data processing, CPET is still a method that is technically challenging. In order
      to obtain reliable results, strict quality control is of crucial importance.
      Additionally, standardization of result display, independent of equipment
      manufacturers or institutions, is desirable, in order to ensure a uniform
      interpretation of results.

PMID- 18814091
TI  - [Dana Point: what is new in the diagnosis of pulmonary hypertension?].
AB  - The hemodynamic definition of pulmonary hypertension (PH) has not been evidence
      based. Normal individuals have a pulmonary pressure of about 14 mm Hg. The
      respective normal range is up to 20 mm Hg. It was decided in Dana Point 2008 to
      introduce new thresholds for mean pulmonary arterial pressure with < 21 mm Hg =
      normal, 21 - 25 mm Hg = borderline, and > 25 mm Hg = manifest PH.
      Correspondingly, echocardiographic systolic tricuspid regurgitant velocity
      thresholds will be < 2.5 m/s = normal, 2.5 - 2.8 = borderline, > 2.8 m/s =
      manifest PH. Confirmation by right heart catheterization is mandatory as many
      false positive readings and patients with undetected diastolic filling
      disturbance can be expected, based on current literature. During exercise, PA
      pressure is strongly age-dependent. Therefore exercise values were left out of
      the definition. Cardiac magnetic resonance imaging (MRI) is expected to gain
      importance for routine examinations in the next years, although currently right
      heart catheterization regains territory. Genetic analysis of BMPR2 gene
      represents an important option for patients with idiopathic PAH and their
      relatives. However, it is not suitable for screening in the general population.
      Follow-up examinations in patients with targeted therapy are very important for
      the definition of specific therapy goals in order to improve prognosis. Future IN
      VIVO tests of vessel properties and right heart function could improve our
      understanding and the development of new therapies.

PMID- 18814092
TI  - [Specific drugs for the treatment of pulmonary arterial hypertension - current
      status].
AB  - For some years drugs of several different classes have been available in Germany
      for the treatment of pulmonary arterial hypertension (PHT): prostanoids,
      endothelin-receptor antagonists and phosphodiesterase inhibitors. To-date all
      relevant studies have consistently shown improvement in the 6-minute walking test
      (Iloprost, Treprostinil, Bosentan, Sitaxentan, Ambrisentan, Sildenafil). Results
      have not been consistent when the end-point has been an improvement in New York
      Heart Association (NYHA) class III or in the time to clinical worsening. Despite
      the good safety data for all drugs approved in Germany in the treatment of PHT,
      there are some clinically relevant interactions and significant
      contraindications. The availability of several options demands a detailed
      knowledge of studies to optimize safety and success in the treatment of PHT.
      Placebo-control mortality studies are not available for ethical reasons for those
      drugs that have been approved in Germany. But cohort analyses using historical
      survival rates have demonstrated a impressive improvement in survival of patients
      with PHT. Although there has been great progress in the treatment of PHT, a cure
      of this grave disease is not yet possible.

PMID- 18814093
TI  - [Combination therapy in patients with pulmonary arterial hypertension].
AB  - Despite recent remarkable efforts in the medical treatment options of patients
      with pulmonary arterial hypertension (PAH) a considerable number of patients need
      escalations to improve disease related symptoms and pulmonary hemodynamics. Most
      of the pulmonary vascular vasodilators have been approved in its potency as an
      initial and sole medical option. However, there is increasing scientific evidence
      on the reliability, safety and effectiveness of possible combinations. This paper
      reviews the current scientific literature about medical escalations and
      combination therapy in patients with PAH.

PMID- 18814094
TI  - [Dana Point: what is new in the treatment of pulmonary hypertension?].
AB  - The treatment algorithm that has recently been developed at the 4th World
      Conference on Pulmonary Hypertension (PH) in Dana Point will contain a number of
      important innovations for patients with pulmonary arterial hypertension (PAH),
      but also for those with other forms of PH. In PAH patients, a targeted therapy
      with ERA or PDE5 inhibitors is now recommended for patients in functional class
      II. Combination therapy (ERA and/or PDE5i and/or prostanoids) is proposed if the
      clinical response to monotherapy is not adequate. In addition, supervised
      training programs are recommended for patients with PAH. For other forms of PH
      such as PH due to left heart disease or chronic lung disease, it remains valid
      that the underlying disease should be treated as efficiently as possible.
      However, a targeted PAH therapy may be beneficial in selected patients with "out
      of proportion PH", but these treatments should exclusively be initiated in expert
      centers. Pulmonary endarterectomy (PEA) remains the treatment of choice for
      chronic thromboembolic pulmonary hypertension (CTEPH). If patients are inoperable
      and/or if surgical treatment is not an option, targeted PAH therapy may be
      considered, but these patients should at present be included into clinical
      trials. Since there is currently no cure for PH/PAH, further development and
      progress in medical treatment are highly desirable. A number of promising novel
      compounds are currently under investigation. These include sGC stimulators,
      tyrosine kinase inhibitors, and serotonin antagonists.

PMID- 18814095
TI  - [Pulmonary hypertension in lung diseases].
AB  - Pulmonary hypertension (PH) eventually occurs during the course of obstructive as
      well as restrictive lung diseases, with highly variable prevalences between the
      different entities. Early detection of PH in patients with manifest lung diseases
      is difficult as PH and lung disease share most clinical symptoms in common.
      Diagnostic hints may come from clinical symptoms - out of proportion dyspnea and
      disability as well as exaggerated hypoxemia with hyperventilation - radiologic,
      ECG, echocardiographic findings, lung function test results, and laboratory
      parameters such as BNP and NT-proBNP are potential indicators of PH. In any case,
      right heart catheter is obligatory to make a firm diagnosis of PH. Optimal
      therapy of the underlying disease including long-term oxygen therapy is the
      mainstay of treatment. In eligible patients lung transplantation is a potentially
      life saving procedure. Specific PAH medications are so far not approved for the
      use in PH associated with lung diseases. Based on pathophysiological similarities
      with PAH and successful case reports specific PAH therapies may be employed "off
      label" in an individual case by case decision. Adequately designed and powered
      clinical trials are urgently needed to confirm the role of PH specific therapies
      in patients with lung disease associated PH.

PMID- 18814096
TI  - [Update in pulmonary hypertension associated with connective tissue diseases - a
      systematic literature review].
AB  - Pulmonary hypertension (PH) is a common complication of connective tissue
      disease. While there are no reliable epidemiological data, the prevalence of
      systemic sclerosis (SSc) has been estimated as being 8-12%. Mixed connective
      tissue disease (MCTD) and systemic lupus erythematodes (SLE) are thought to have
      a lower prevalence. PH associated with SSc has a poor prognosis, a two-year
      survival rate of approximately 50%, if untreated. Systematic literature search
      for studies of PH and CTD between 02/2007 and 02/2008 found 38 articles, a
      selection of which is reviewed here. One epidemiological study showed that
      nowadays PH is together with interstitial pulmonary fibrosis the most common
      cause of death in patients with SSc. Before the introduction of angiotensin-
      converting enzyme inhibitors the most frequent cause of death was acute renal
      crisis. Investigations of the pathogenesis of PH in CTD revealed that in patients
      with a severe, treatment-resistant course there is frequent histological evidence
      of pulmonary veno-occlusive disease. A prospective study on diagnosis revealed
      that transthoracic echocardiography (TTE) is better than magnetic resonance
      imaging or pulmonary function tests especially in screening for PH in patients
      with SSc, because of its high specificity and good predictive value at higher
      pulmonary pressures. But because of the low sensitivity of TTE right heart
      catheterization is the gold standard for verifying PH also in patients with SSc.
      A therapeutic uncontrolled trial indicated that treatment with bosentan combined
      with sildenafil results in clinical stabilization, but patients with idiopathic
      PHT responded better.

PMID- 18814097
TI  - ["Pulmonary hypertension" of the gastrointestinal tract in patients with systemic
      sclerosis: thoughts on a not (yet) existing disease entity].
AB  - Vascular changes are often found in numerous organs of patients with systemic
      sclerosis (SSc). It has been shown that, e.g. Raynaud's syndrome, ulcers of the
      digits and pulmonary arterial hypertension have similar patterns of endothelial
      dysfunction. There is evidence of gastrointestinal complications in almost all
      patients with SSc, most often caused by abnormal motility and fibrosis.
      Immunohistological studies have shown that gastric and intestinal mucosae have
      not only activation of classical activation markers and adhesion molecules, but
      also of growth factors demonstrated in pulmonary hypertension as well as
      overexpression of endothelin-1. The possible common pathogenesis of he
      vasculopathies in the lung and gastrointestinal tract suggests that explorative
      studies should be undertaken in which endothelin-receptor antagonists are
      administered to patients with abnormal gastrointestinal motility and SSc.

PMID- 18814098
TI  - [Chronic thromboembolic pulmonary hypertension (CTEPH)].
AB  - The spectrum of venous thromboembolism encompasses deep vein thrombosis, acute
      thrombus passing through the right heart, acute pulmonary embolism and chronic
      thromboembolic pulmonary hypertension (CTEPH). Pulmonary embolism may recur and
      have severe sequelae, such as the post-thrombotic syndrome and CTEPH. It is
      thought at present, based on a long-term prospective study of about 300 patients,
      that CTEPH results within two years in 3.8% of patients who had survived the
      first symptomatic pulmonary embolism. Previous incidence of pulmonary embolism,
      young age, a large perfusion deficit and no known cause were associated with an
      increased probability of subsequent CTEPH. The diagnosis and treatment of CTEPH
      call for an interdisciplinary approach, the former still relying on finding a
      positive perfusion scan together with pulmonary hypertension. Treatment of choice
      is surgical endarterectomy of the pulmonary obstruction which will result in
      functional healing in 80% of patients.

PMID- 18814099
TI  - [Pharmacological treatment of pulmonary hypertension in patients with congenital
      heart disease].
AB  - The development of drugs for lowering pressures in pulmonary arterial
      hypertension (PHT) has provided possible therapeutic application in patients with
      pulmonary hypertension associated with congenital heart disease (CHD).
      Prostanoids, both nonselective and selective endothelin-receptor antagonists and
      phosphodiesterase-V inhibitors have been used for this purpose. The efficacy of
      these drugs - from different classes of bioactivity - in this context have been
      shown in several studies. However, the long-term effects of drug treatment on
      prognosis and course of PHT have not yet been adequately investigated. The
      current status of drug treatment of PHT in patients with CHD is reviewed in this
      article.

PMID- 18814100
TI  - [Pulmonary veno-occlusive disease - a rare form of pulmonary arterial
      hypertension].
AB  - Pulmonary veno-occlusive disease (PVOD) is a rare cause of pulmonary
      hypertension. So far some 200 cases have been published worldwide. Since the
      latest classification, agreed at a meeting in Venice in 2003, PVOD is included in
      the group of pulmonary arterial hypertension (PAH). It has been hypothesized that
      it represents endothelial dysfunction of unknown cause. Although it has many
      features in common with idiopathic PAH, it partially differs from it
      phenotypically. After exclusion of known causes of pulmonary hypertension, such
      as diseases of pulmonary interstitial tissue, acral clubbing and rales suggest
      PVOD. The findings typical in the computed tomogram of the chest include
      prominent septal lines, centro-acinar opacities and mediastinal lymphadenopathy.
      In addition to arterial lesions PVOD is particularly characterized by lesions in
      the venous vascular bed. PVOD has a poor prognosis. Treatment with medication
      approved for PAH may carry the risk of pulmonary edema. Currently the immediate
      listing for lung- or combined lung-heart-transplantation is recommended, once the
      diagnosis of PVOD has been established.

PMID- 18814101
TI  - [Decompensated pulmonary hypertension].
AB  - Right ventricular failure may result from an newly developed disease (e.g. as a
      consequence of acute respiratory distress syndrome [ARDS] or of severe pulmonary
      embolism) or of already present pulmonary hypertension (PHT). There is as yet no
      generally recognized definition of acute or chronic right ventricular failure.
      The particular clinical picture and the associated hemodynamics determine this
      condition. Right ventricular failure in the course of PHT represents a great
      challenge in clinical and intensive care practice. Once the vicious circle of
      right heart failure is reached an optimal balance has to be found between preload
      and afterload. In addition to optimizing blood volume, positive inotropic drugs
      (e.g. dobutamine) are available to maintain systemic blood pressure. Furthermore
      an increase in right ventricular contractility by inodilators is aimed at. The
      central goal in the treatment of right heart failure as part of PHT is to lower
      pulmonary vascular resistance and thus decrease right ventricular afterload.
      However, it is very difficult to break the vicious circle involved in the acute
      right heart syndrome, it must be the primary aim of treatment to recognize as
      early as possible any worsening of PHT and prevent acute right heart failure.
      Lung transplantation or surgical atrioseptostomy may represent possible ultimate
      therapeutic options for patients with PHT.

PMID- 18814102
TI  - Unicuspid aortic valve disease: a magnetic resonance imaging study.
AB  - PURPOSE: Congenitally malformed aortic valves are a common finding in adults with
      aortic valve disease. Most of these patients have bicuspid aortic valve disease.
      Unicuspid aortic valve disease (UAV) is rare. The aim of our study was to
      describe valve morphology and the dimensions of the proximal aorta in a cohort of
      12 patients with UAV in comparison to tricuspid aortic valve disease (TAV) using
      magnetic resonance imaging (MRI). MATERIALS AND METHODS/RESULTS: MRI studies were
      performed on a 1.5 T scanner in a total of 288 consecutive patients with aortic
      valve disease. 12 aortic valves were retrospectively classified as UAV. Annulus
      areas and dimensions of the thoracic aorta were retrospectively compared to a
      cohort of 103 patients with TAV. In UAV, valve morphology was unicuspid
      unicommissural with a posterior commissure in all patients. Mean annulus areas
      and mean diameters of the ascending aorta were significantly greater in UAV
      compared to TAV (12.6 +/- 4.7 cm (2) vs. 8.7 +/- 2.3 cm (2), p < 0.01 and 4.6 +/-
      0.7 cm vs. 3.6 +/- 0.5 cm, p < 0.0001, respectively), while no differences were
      observed in the mean diameters of the aortic arch (2.3 +/- 0.6 cm vs. 2.3 +/- 0.4
      cm, p = 0.69). The diameters of the descending aorta were slightly smaller in UAV
      compared to TAV (2.2 +/- 0.5 cm vs. 2.6 +/- 0.3 cm, p < 0.05). CONCLUSION: In
      UAV, visualization of valve morphology by MRI is possible with good image
      quality. Valve morphology was classified as unicuspid unicommissural in all UAV
      patients. Dilatation of the proximal aorta > 4.5 cm is a frequent finding in UAV.
      Additional assessment of aortic dimensions is therefore recommended in patients
      with UAV.

PMID- 18814103
TI  - [Assessment of the solid-liquid behavior of the liver for the diagnosis of
      diffuse disease using magnetic resonance elastography].
AB  - PURPOSE: Recent magnetic resonance elastography (MRE) studies have reported the
      potential of this noninvasive method for diagnosing hepatic fibrosis based on the
      elastic properties of liver tissue. However, in many cases biological tissue
      responds to mechanical vibrations as a combined solid-liquid body causing MRE
      derived elastic parameters to become functions of the applied vibration
      frequency. Therefore a multi-frequency MRE study of liver was performed and the
      potential of the method for separating healthy from fibrotic liver was
      investigated. The aim of this study was the increase of the accuracy of liver
      elastography by analyzing multi-frequency MRE examinations using the springpot
      model. MATERIALS AND METHODS: 18 healthy volunteers and 10 patients were examined
      by multi-frequency MRE of the liver in a frequency range between 25 Hz and 62.5
      Hz. The liver was mechanically excited with four harmonic vibrations
      simultaneously. The measured dispersion of the complex modulus was analyzed using
      the springpot model which accounts for both elastic and viscous properties of a
      material with 2 independent parameters. RESULTS: The mechanical stimulation and
      the motion encoding according to the multi-frequency approach was implemented
      successfully. Significant differences (p < 0.05) were found in the hepatic
      viscoelasticities of normal livers. The separation of healthy volunteers and
      patients was achieved with a sensitivity and specificity of 80 and 100 %,
      respectively. CONCLUSION: Using the springpot model, multi-frequency MRE is
      sensitive to interindividual differences in the hepatic viscoelastic properties
      of healthy volunteers. The obtained accuracy of the technique in separating
      healthy from fibrotic livers opens the possibility of applying multi-frequency
      MRE as a noninvasive method for diagnosing liver fibrosis in the future.

PMID- 18814104
TI  - [Neurogenic communication disorders: how effective are relaxation therapy and
      acupuncture?].
AB  - Not only neurologists but also ENT-physicians and phoniatricians have to
      prescribe speech and language therapy for patients with communication disorders.
      Complementary and alternative medicine (CAM) has gained increasing popularity
      among patients. Many studies have investigated these procedures and positive
      effects on certain physical e. g., chronic pain and anxiety disorders could be
      validated. Unfortunately only few empirical investigations have targeted the use
      of CAM to treat neurogenic disorders of communication or cognition. In this
      review we provide an overview over general therapeutical principals of two widely
      used approaches, relaxation therapy and acupuncture. Then we survey the
      literature and summarize existent research literature regarding the effects of
      the treatment of neurogenic disorders including dementia.

PMID- 18814105
TI  - [Two- and three-dimensional, morphologic and functional MR-imaging in smelling
      disorders].
AB  - Olfactory dysfunction is a frequent diagnosis. This overview describes recent
      standards in structural imaging related to olfactory dysfunction, with magnetic
      resonance imaging being the most significant imaging tool both quantitatively and
      qualitatively. Relevant MRI-techniques to be applied in patients during routine
      clinical workup and the consecutive imaging evaluation are presented and
      discussed.

PMID- 18814106
TI  - [Selective internal radiotherapy for advanced liver tumors and metastases].

PMID- 18814107
TI  - The importance of macroprolactinemia in the differential diagnosis of
      hyperprolactinemic patients.
AB  - OBJECTIVE: Hypersecretion of prolactin (PRL) by lactotroph cells of the anterior
      pituitary may lead to hyperprolactinemia in physiological or pathological
      conditions. However, some of the patients may present with another cause of
      hyperprolactinemia, described by various authors as macroprolactinemia. PATIENTS
      AND METHODS: The clinical, radiological and biochemical assessment of 124
      patients were carefully evaluated for differential diagnosis in light of the
      literature. Macroprolactinemia was assessed by the polyethylene glycol (PEG)
      method in all of the patients, with high PRL level but without significant
      symptomatology, presenting to our clinic between 2004 and 2006. RESULTS: The sera
      from 124 patients with hyperprolactinemia were screened for macroprolactinemia
      using the PEG method and macroprolactinemia was detected in 10 patients (8%). The
      average age of the patients was 35 years (range 23-46). Nine of the ten patients
      were female (90%) and one was male (10%). All of the patients had MRI. An
      intrasellar mass and stalk lipoma were found in three of the ten patients (30%).
      CONCLUSIONS: In conclusion, macroprolactinemia should be taken into consideration
      as a probable cause of high serum prolactin levels to avoid repeated hormone
      assessments, neuroradiological examinations and unnecessary medical and surgical
      treatments.

PMID- 18814108
TI  - The incidence of berry aneurysm in the Iranian population: an autopsy study.
AB  - Intracranial berry aneurysms are the most common kind of aneurysms in the brain,
      and are caused by head trauma in 1% of cases. They may remain asymptomatic for a
      long time or may rupture and cause intracranial hemorrhage. These aneurysms are
      associated with a high mortality rate. A definitive diagnosis can be made by
      angiography or autopsy. We studied the cadavers of 425 people who passed away
      accidentally. The number and location of berry aneurysms were recorded. Twelve
      cases (2.82%) were found to have a single berry aneurysm and two (0.47%) had
      multiple aneurysms. The aneurysms had a tendency to occur in the frontal half of
      the Circle of Willis and in approximation of the bifurcation of arteries. The
      main characteristics of cases of berry aneurysm in the Iranian population were in
      agreement with that reported in previous Western studies.

PMID- 18814109
TI  - A rare case of pituitary adenoma with calcification: a case report.
AB  - Though craniopharyngioma remains the most common sellar suprasellar tumor with
      calcification, it can be seen very rarely in pituitary adenomas and Rathke's
      cleft cysts. Appreciation of the pattern of calcification in a sellar suprasellar
      lesion can give a clue to the nature of the lesion. The authors describe a 53
      yearold male with a cystic sellar suprasellar lesion and curvilinear
      calcification that was managed by successful transsphenoidal surgery. The present
      case highlights the occurrence of calcification in a pituitary adenoma and the
      importance of recognizing the calcification pattern for pre-operative diagnosis
      of sellar suprasellar lesions that can help plan the surgical strategy and
      management.

PMID- 18814110
TI  - A non-bleeding complex intracerebral giant aneurysm case: case report.
AB  - An intracranial aneurysm with a diameter larger than 25 mm is considered a giant
      aneurysm (GA), and represent about 3-5% of all aneurysms. They are divided into
      two forms, specifically saccular and fusiform. Fusiform aneurysms are rare,
      making up only 1% of all intracranial aneurysms. They frequently involve the
      internal carotid artery (ICA) or the basilar or vertebral arteries, and rarely
      bleed. Treatment of huge aneurysms that have not bled is still controversial.
      Unlike the saccular huge aneurysms that lead to death of 80% of the patients few
      years after diagnosis, fusiform huge aneurysms, particularly those presenting
      with mass effect, have a better prognosis. In this manuscript, we discuss the
      infrequently seen intracranial fusiform giant aneurysms in light of the pertinent
      literature.

PMID- 18814111
TI  - Cervical intradural ventral arachnoid cyst resected via anterior corpectomy with
      reconstruction: a case report.
AB  - Intradural arachnoid cysts are rare lesions that frequently arise posterior to
      the spinal cord in the thoracic spine region. Those located at the cervical spine
      level, anterior to the spinal cord are even rarer. The usual treatment of
      symptomatic intradural spinal cysts involves surgical removal through a posterior
      approach using a laminectomy or laminotomy. However, ventrally located intradural
      cysts are frequently not amenable to complete resection without undue
      manipulation of the cord and aggressive removal through a posterior approach may
      result in spinal cord injury. The authors present a 29-year-old male harbouring
      an intradural ventral cervical arachnoid cyst which was successfully resected via
      an anterior approach with corpectomy and reconstruction. CONCLUSION: For purely
      ventral cervical intradural arachnoid cysts, which compress the spinal cord
      dorsally, an anterior approach can allow access to the lesion without any need
      for intraoperative manipulation of the spinal cord. For such cases, the anterior
      approach prevents the consequent risk of neurological injury due to posterior
      approaches.

PMID- 18814112
TI  - Iliocaval arteriovenous fistula following lumbar disc surgery: endovascular
      treatment with a Stent-graft.
AB  - Arteriovenous (AV) fistulae, pseudoaneurysms, and lacerations may occur during
      disc surgery. AV fistula after lumbar disc surgery is rare. Early diagnosis and
      treatment of vascular complications associated with disc surgery is essential due
      to their high mortality and morbidity rates. We report a case report who was
      presented with fistulous shunt between right common iliac artery and inferior
      vena cava fifteen days after operation for herniated discs at L4-L5 and L5-S1
      levels. Treatment was transcatheter covered stent placement at the fistulous site
      of right common iliac artery using a self expandable stent-graft. We suggest use
      of minimally invasive interventional techniques in the management of suitable
      vascular injuries following lumbar disc surgery.

PMID- 18814113
TI  - Chondromyxoid fibroma of frontal bone: a case report and review of the
      literature.
AB  - Chondromyxoid fibroma is an unusual benign tumor of cartilaginous tissues that
      may be confused with other some malign tumors. It is rarely seen in the skull. A
      45-year-old female was admitted with painless bony swelling in the forehead.
      Computerized tomography demonstrated a well-defined expansive lesion with a
      sclerotic margin measuring approximately 3 cm in diameter in the right frontal
      bone. On MRI, T1-weighted images revealed a well circumscribed, lobulated and
      strongly enhancing lesion. On the T2-weighted images, the lesion showed high
      heterogeneous signal intensity. The patient underwent tumor excision with
      craniectomy, then acrylic cranioplasty. The histopathological diagnosis was
      chondromyxoid fibroma. There was no recurrence in a period of 22-months. In
      conclusion, chondromyxoid fibroma is a benign primary bone tumor that is located
      extremely rarely in the frontal bone. Accurate initial diagnosis of such tumors
      are important for appropriate treatment. En block surgical resection of the tumor
      is the cornerstone of treatment.

PMID- 18814114
TI  - The shrinking of an anterior sacral meningocele in time following transdural
      ligation of its neck in a case of the Currarino triad.
AB  - In this paper we present an adult patient with the Currarino triad, associated
      with six habitual abortuses and chronic constipation. Our aim is to report the
      effectiveness of a simple surgical technique in the treatment of anterior sacral
      meningocele in the Currarino Syndrome. The presentation of the Currarino Syndrome
      in adulthood is extremely uncommon. We performed a posterior procedure via lumbar
      and sacral partial laminectomy and transdural ligation of the neck of the
      meningocele mass. There were no additional neurological deficits and no
      recurrence of the presacral mass over the 2-year follow up period. When an adult
      female with habitual abortus and chronic constipation is seen, the possible
      presence of the Currarino Triad should be investigated and treated. The anterior
      sacral meningocele in a case of the Currarino Triad regresses over time following
      transdural ligation of its neck.

PMID- 18814115
TI  - Gangliocytoma associated with focal cortical dysplasia in a young-adult: a case
      report.
AB  - Neoplasms and (non-neoplastic) focal dysplasias may coexist as a cause of
      seizures in both the developing and mature brain. Low grade neoplastic lesions
      (ganglioglioma/gangliocytoma) may present with seizures, and distinction of these
      lesions from focal cortial dysplasia is difficult on standard radiological
      imaging. We report a 24-year-old man who had complaints of tonic-clonic seizures
      for one week duration and was admitted to department of neurosurgery. He did not
      have any neurological deficit on his examination. Cranial computerized tomography
      and magnetic resonance imaging of the patient revealed a calcified, cystic lesion
      with contrast enhancement, in the left temporoparietal region. Subtotal resection
      of the mass was performed. Pathological examination revealed focal cortical
      dysplasia associated with gangliocytoma.

PMID- 18814116
TI  - Transient lesion in the splenium of the corpus callosum due to carbamazepine.
AB  - Keeping in mind that lesions located in the splenium of the corpus callosum can
      sometimes be temporary may help us avoid invasive diagnostic and therapeutic
      methods. Transient lesion in the splenium of the corpus related to using or
      withdrawal of antiepileptic drugs are rarely encountered. In this article, we
      present a non-epileptic patient found to have a centrally located isolated lesion
      in the splenium of the corpus callosum on the tenth day following the sudden
      withdrawal of carbamazepine after two weeks of use. The lesion was observed to
      disappear two months later and the carbamazepine treatment or sudden withdrawal
      of the drug was thought to be responsible for this reversible splenial lesion.

PMID- 18814117
TI  - Transmandibular approach for upper cervical pathologies: report of 2 cases and
      review of the literature.
AB  - In routine surgical practice, anterior approaches are not often used to treat
      upper cervical pathologies. Such lesions can be difficult to access surgically.
      This article describes 2 cases in which the transmandibular approach was used to
      address anterior upper cervical pathology. One case was a chordoma invading the
      C2-C3 vertebrae and the other case was atlanto-axial instability. Neurological
      examination revealed myelopathy in both cases. Each patient had already undergone
      occipito-cervical fusion at a different center and, thus, had limited neck
      extension and mouth-opening ability. In the first case, the tumor was totally
      excised. In the second, the dens was removed. We believe that the transmandibular
      approach is the best option for patients with limited neck mobility and
      restricted mouth-opening ability.

PMID- 18814118
TI  - Unusual massive spinal metastasis of an intracranial oligodendroglioma.
AB  - Herein, we present a case of anaplastic oligodendroglioma with massive spinal
      metastasis in the first post-operative year without any residual tumor or
      recurrence in the primary tumor site. Along with the reported literature, our
      case highlights the importance of periodic radiological evaluation of the spinal
      canal including the pre- and post-treatment period, in patients with
      intracerebral oligodendroglioma.

PMID- 18814119
TI  - Meningoencephalocele formation after nasal septoplasty and management of this
      complication.
AB  - OBJECTIVE: Patients undergoing nasal septoplasty can face many complications.
      Some of these complications are rare but their results are life threatening.
      Being aware of this complication could prevent further problems such as
      enlargement of the bone and dural defect, herniation of the meninges and brain
      tissue through the defect by pulsation of the brain and ascending infection. With
      early diagnosis, a less aggressive method could be used to treat this
      complication. CASE DESCRIPTION: A 50-year-old woman was admitted our hospital
      with the complaint of loss of consciousness. Her Glasgow coma score was 7 on
      admission. She had no lateralizing signs, but had nuchal rigidity. Blood pressure
      was 200/110mm Hg, the respiratory pattern was apneic, complete blood count
      revealed 12000 leucocytes/mm3 and arterial blood gases showed respiratory
      acidosis and other biochemical parameters were within normal limits. Computerized
      cranial tomography (CCT) showed diffuse brain edema without evidence of other
      signs. Lumbar puncture was performed revealing purulent and highly viscous
      cerebrospinal fluid (CSF). CONCLUSION: Late diagnosis and late repair of
      arachnoidodural tearing could lead to life-threatening complications, and cases
      with meningitis and larger defects may require more extensive surgery instead of
      transnasal endoscopic repair.

PMID- 18814120
TI  - Surgical treatment of lesions involving the supplementary motor area: clinical
      results of 12 patients.
AB  - AIM: Surgical resection of lesions involving the dominant supplementary motor
      area (SMA) may result in immediate postoperative motor and speech deficits which
      in most cases are reversible.We report 12 patients with frontal lesions involving
      the SMA and aim to analyse the clinical data and the correlation of neurological
      deficit with the extent of SMA resection. MATERIAL AND METHODS: 12 patients
      (5M/7F, mean age 30.5) harbouring lesions involving the SMA who underwent surgery
      between 2002-2007 were evaluated retrospectively. Eloquent cortical areas were
      determined by functional MRI studies and/or invasive monitoring with subdural
      grids and depth electrodes and/or awake craniotomy with continuous intraoperative
      monitoring. RESULTS: The evaluation of postoperative MRI's revealed total and
      subtotal resection of the lesion in 9(75%) and 3(25%) patients respectively. The
      extent of SMA resection was complete in 5 patients (41,6%) and incomplete in 7
      patients (58,3%). Immediately postoperatively, all patients where the resection
      of SMA was complete displayed the typical characteristics of SMA syndrome. The
      degree of deficits was consistent with the extent of the SMA resection in all
      patients. CONCLUSION: Proper diagnostic methods aiming to localise the
      sensorimotor area can minimize the risk of deficit in the surgical treatment of
      SMA lesions. The results suggest a relationship between the incidence of SMA
      syndrome and the extent of SMA resection.

PMID- 18814121
TI  - Isolated spinal neurocysticercosis with clinical pleomorphism.
AB  - Neurocysticercosis, involvement of the central nervous system by taenia solium,
      is one of the most common parasitic diseases worldwide. However, isolated spinal
      involvement by neurocysticercosis, either intramedullary or extramedullary, is
      uncommon. The authors report a case of C1-C2 intradural extramedullary
      neurocysticercosis in a young male that presented initially with signs of raised
      intracranial pressure followed by high cervical myelopathy. Transventricular
      migration of the neurocysticercal cyst along the cerebrospinal pathways leading
      to clinical pleomorphism as described by the authors can perplex the best of
      clinicians leading to a missed diagnosis as in the present case. Diagnosis was
      confirmed after surgical excision and the patient is doing well at six months
      follow up with no neurological deficits. Spinal neurocysticercosis should be
      considered in the differential diagnosis in high-risk populations with new
      symptoms suggestive of a spinal mass lesion.

PMID- 18814122
TI  - Stab injury of the thoracic spinal cord: case report.
AB  - Stab injuries of the spinal cord are rare. We report a case of a 22-year-old male
      who was hospitalized because of a spinal cord injury resulting from a stab wound
      in the posterior thoracolumbar area. On admission, the patient had 2/5 muscle
      strength of the right leg (monoparesis) and hypoesthesia below the L1 level.
      Radiological investigation revealed the retained tip of a knife that penetrated
      the spinal canal at the T12 level. An urgent right T12 hemilaminotomy was
      performed and retained knife fragment was removed. Six months after operation,
      the motor deficit had completely improved although hypoesthesia was still
      present. Surgery should be considered as the first-line treatment in cases of
      incomplete injuries of the spinal cord with retained metallic object.

PMID- 18814123
TI  - A large choroid plexus papilloma removed by the cerebellomedullary fissure
      approach. Case report and review of the literature.
AB  - We report a case of large choroid plexus papilloma of the fourth ventricle in a
      23-year-old woman. She presented with severe headache, dysphagia, and gait
      disturbances. Horizontal nystagmus, ataxic gait and quadriparesis were detected
      on initial examination. Imaging studies showed a large mass in the left side of
      brain stem and a marked hydrocephalus. The tumour was removed by microsurgical
      dissection of the cerebellomedullary fissure. We have discussed the effectiveness
      of this approach for removal of bulky tumors of the fourth ventricle and reviewed
      the literature about its benefits and potential hazards.

PMID- 18814124
TI  - CT-guided corticosteroid injection as a therapeutic management for the pyriformis
      syndrome: case report.
AB  - The pyriformis syndrome is a rare entrapment neuropathy in which the sciatic
      nerve is compromised by the pyriformis muscle or other local structures. It is an
      important cause of buttock pain that may often be accompanied by sciatica. The
      pain is usually increased by muscular contraction, palpation or prolonged
      sitting. The diagnosis relies on the clinical presentation and the
      electromyelography (EMG) findings. Other causes of symptoms should be excluded by
      careful examination and detailed neuroradiological studies of the lumbosacral
      spine, sacro-iliac and hip joints. A case of this syndrome seen in a 36-year-old
      man who recovered by CT-guided corticosteroid injection is reported.

PMID- 18814125
TI  - Repair of wide myelomeningocele defects with the bilateral fasciocutaneous flap
      method.
AB  - OBJECTIVE: Five large myelomeningocele defects repaired by bilateral
      fasciocutaneous flaps are presented in this article. PATIENTS AND METHODS: After
      the neurological repair, bilateral fasciocutaneous flaps were raised, transposed
      over the midline, and sutured to each other. RESULTS: All operations lasted
      shorter than one hour and no major complication was noted in the follow-up. Three
      of the defects were in the thoracolumbar and two in the lumbosacral regions. The
      areas of the defects were between 5x6 cm (30 cm2) and 8x10 cm (80 cm2).
      CONCLUSION: The bilateral fasciocutaneous flap technique offers a shorter
      operation duration and lower bleeding rate; it is simple to learn and practice
      and does not abolish alternative operation techniques.

PMID- 18814126
TI  - Tentorium schwannoma mimicking meningioma: an unusual location.
AB  - A 60-year-old female was admitted to our clinic complaining of a long-lasting
      headache. Cranial magnetic resonance imagining examination of the patient
      revealed a 22x24 mm extra-axial, well-demarcated, mass lesion based on the left
      tentorium. The patient underwent a craniotomy and the tumor was totally excised
      with the adjacent tentorium. The histopathological examination of the tumor
      complied with the diagnosis of schwannoma. The rest of the clinical course was
      uneventful and the patient was released from the hospital without any
      neurological deficit. Intracranial schwannomas can rarely originate from atypical
      dural locations and radiological techniques are not always helpful in
      distinguishing tentorial schwannoma from tentorial meningioma. We presented a
      patient with a tentorium schwannoma mimicking meningioma and discussed the
      current literature.

PMID- 18814127
TI  - Spinal schwannomatosis: case report of a rare condition.
AB  - Schwannomatosis is a rare tumour syndrome characterized by more than one
      schwannoma without any sign of neurofibromatosis (NF). A 22-year-old male patient
      was admitted with weakness in his extremities. Neurological examination revealed
      a tetraparesis syndrome below the C6 level. Magnetic resonance (MR) imaging
      showed a demarcated mass with strong enhancement at the C4-7 levels. The patient
      improved rapidly after removal of the tumour. The histological diagnosis was
      schwannoma. Two years later, the same patient was admitted with the complaint of
      severe low back and leg pains. The neurological examination was normal except
      bilateral positive straight leg raising test and dysesthesia at the L3,4 and 5
      dermatomes. MR showed a wellcircumscribed lesion at L4-5. Laminectomy and tumour
      excision relieved his complaints. The histological diagnosis was schwannoma. A
      detailed clinical examination and MR scanning of the central nervous syndrome
      excluded NF2. In conclusion, although schwannomatosis is a benign condition,
      symptomatic tumours should be resected surgically.

PMID- 18814128
TI  - Spinal subdural hematoma: a rare complication of spinal anesthesia: a case
      report.
AB  - Spinal hematoma is an infrequently described complication of spinal anaesthesia.
      It has been described in the literature in patients with a deranged coagulation
      profile in the form of systemic diseases (e.g. chronic renal failure, liver
      failure) or anticoagulant therapy. Whatever the reason, it will have disastrous
      consequences in the form of permanent paraplegia or persistent neurological
      deficit if not treated promptly. One therefore needs to maintain a high index of
      suspicion at all times in any patient who has undergone spinal anesthesia and who
      exhibits any sign or symptom of a neuraxial hematoma We report a case of post
      spinal puncture subdural hematoma in an otherwise healthy male without any
      predisposing factor.

PMID- 18814129
TI  - CT and MRI findings in X-linked progressive deafness.
AB  - Congenital X-linked mixed deafness is a rare anomaly that has typical features
      and can be diagnosed on the basis of progressive mixed hearing loss and the
      typical imaging findings. Recognition of these findings may alter the course of
      treatment and perilymph gushing can be avoided. A 10-year-old male patient
      presented with a history of progressive hearing loss. Computed tomography of the
      temporal bones showed bulbous dilatation of the fundi of the internal auditory
      canals (IAC) and the absence of the bony plates separating the basal turn of the
      cochleas and IAC. Magnetic resonance imaging demonstrated obliteration of the
      labyrinthine spaces at the right side.

PMID- 18814130
TI  - Fallen lung sign: radiographic findings.
AB  - The term "fallen lung sign" refers to the collapsed lung in a dependent position,
      hanging on the hilum only by its vascular attachments. This is usually the result
      of the complete rupture of a bronchus. On chest radiograph, the diagnosis of
      bronchial tear is usually suspected with the persistence of a pneumothorax after
      chest tube insertion. An 8-year-old male patient had radiographic findings of
      persistence of right pneumothorax which was due to complete rupture of the right
      main bronchus, resulting in fallen lung.

PMID- 18814131
TI  - Variations in breast doses for an automatic mammography unit.
AB  - PURPOSE: To assess variations of glandular doses for a group of patients when
      different dose modes are selected for a specific system. MATERIALS AND METHODS:
      All measurements were obtained with a Senographe DMR mammography unit (GE Medical
      Systems). Automatic exposure control with either contrast or standard mode was
      routinely used in patient examinations. Entrance surface air kerma (ESAK) values
      were estimated from the postexposure mAs and from the recorded data. Subsequently
      the mean glandular dose (MGD) for each view was calculated using the conversion
      factors assuming 50% glandular and 50% adipose tissue composition. RESULTS: The
      average MGD for the right craniocaudal view for all beam qualities was 1.65 mGy,
      and 46.7 mm was the average compressed breast thickness for this view. Average
      MGDs were 1.61, 1.76, and 1.35 mGy for Mo-Mo, Mo-Rh, and Rh-Rh anode filter
      selections, respectively. Conversely, 2.18 and 1.47 of breast doses were measured
      for contrast and standard dose modes at the most often used (Mo-Mo) anode filter
      selection. CONCLUSION: Breast dose measurement techniques with the standard
      phantom or on real patients are easy to implement for the mammography users.
      Obtaining ESAK versus breast thickness relationship is useful for retrospective
      dose evaluation; better correlation can be established (67% vs. 52%) if they are
      generated separately for each dose modes.

PMID- 18814132
TI  - Vacuum-assisted breast biopsy in nonpalpable solid breast lesions without
      microcalcifications: the Greek experience.
AB  - PURPOSE: To present the initial Greek experience with vacuumassisted breast
      biopsy (VABB) in the diagnosis of nonpalpable solid mammographic lesions without
      microcalcifications. MATERIALS AND METHODS: We performed 83 VABB procedures
      (using a Fischer table and 11-guage Mammotome probes) in an 18- month period on
      women with nonpalpable solid breast tumors. We performed VABB procedures on women
      with breast imaging reporting and data system (BI-RADS) categories 3 and 4. VABB
      procedures excised more than 24 cores. RESULTS: Eighty-three women with
      nonpalpable lesions identified on mammography were evaluated; 42.2% were BI-RADS
      category 3, and 57.8% were BI-RADS 4. Of all solid tumors excised, 83.1% were
      benign, 3.6% were precursor lesions, and 13.3% of the lesions were malignant. No
      underestimation occurred. Clinically important hematoma developed in 4.8% of
      cases. CONCLUSION: VABB is an effective method for the diagnosis of nonpalpable
      solid lesions because of the lack of underestimation, although it is technically
      more difficult to focus on lesions without microcalcifications than those with
      microcalcifications on the Fischer table.

PMID- 18814133
TI  - A simple method to decrease surgical trauma in wire localization procedures.
AB  - Minimally invasive breast biopsies of nonpalpable lesions are used for early
      diagnosis and treatment of breast cancer. This report describes a simple method
      to decrease surgical trauma in wire localization procedures. After wire
      localization with mammography or ultrasound, the course of the wire in the breast
      was marked on the skin to guide the surgeon. As a result, fewer tissue samples
      were taken and smaller hematomas occurred. This method is particularly useful in
      deep lesions and in large breasts, leading to shortened surgery time and improved
      cosmetic results. This technique can be used in any wire-guided procedure.

PMID- 18814134
TI  - Prevalence of abdominal ultrasonographic abnormalities in patients with sickle
      cell disease.
AB  - PURPOSE: The aim of this study was to evaluate the type and prevalence of
      abdominal ultrasonographic abnormalities in patients with sickle cell disease.
      MATERIALS AND METHODS: A total of 102 patients with sickle cell disease at the
      Center of Hemoglobinopathy of the Antakya State Hospital were screened for intra
      abdominal abnormalities by abdominal ultrasonography (US). Eightyfour patients
      were homozygous for sickle-cell disease (S/S), and 18 patients were compound
      heterozygotes for sickle cell-Beta thalassemia (S/Beta(thal)). At the time of
      examination, 15.7% (16/102) of patients had undergone splenectomy, and 18.6%
      (19/102) of patients had undergone cholecystectomy. RESULTS: The most frequent US
      findings (expressed as percentages of all patients) were hepatomegaly (71.6%),
      renal enlargement (30.4%), autosplenectomy (33.3%), cholelithiasis (30.4%) and
      splenomegaly (17.4%). A bright liver was identified in 6 patients (5.9%), an
      echogenic pancreas in 4 patients (3.9%), and pancreatic punctate echogenic foci
      were identified in 5 patients (4.9%). Medullary or diffusely increased renal
      echogenicity was observed in 16 patients (15.7%). Sonographic findings typical of
      renal papillary necrosis were observed in one patient with S/S. Periportal
      lymphadenopathy was detected in 10 (11.9%) of 84 patients of the S/S group, and 2
      (11.1%) of 18 patients of S/Beta(thal) group. CONCLUSION: Abdominal
      ultrasonographic imaging of patients with sickle cell disease revealed a high
      prevalence of abdominal abnormalities, especially in solid organs.

PMID- 18814135
TI  - Effect of subclinical Helicobacter pylori infection on gastric wall thickness:
      multislice CT evaluation.
AB  - PURPOSE: To evaluate the effect of subclinical Helicobacter pylori infection on
      the gastric wall thickness with multislice computed tomography (MSCT). MATERIALS
      AND METHODS: In 99 subjects without gastric disease, CT scans of the abdomen were
      obtained after water ingestion and intravenous contrast administration. CT images
      were evaluated for degree of luminal distention and the thickness of the walls of
      the gastric antrum and body. We also looked for other radiological signs of
      gastritis such as the presence of fold thickening, mucosal enhancement,
      submucosal hypodensity, focal gastric mass-like lesion, and focal wall
      thickening. All subjects were tested with rapid urease test or stool antigen test
      and grouped as H. pylori positive or negative according to the results. RESULTS:
      The average gastric body and antrum wall thicknesses did not show statistically
      significant difference between H. pylori positive and negative groups. The
      average antral wall thickness was greater than the gastric body wall thickness in
      68.5% of cases, independent of H. pylori positivity; and antral wall thickness
      was more than 5 mm in more than 50% of cases. There were no significant
      differences between the groups in terms of other signs of gastritis. CONCLUSION:
      Wall thickening of gastric antrum relative to gastric body is a common finding
      even in the use of MSCT, and antral thickness commonly exceeds 5 mm. Subclinical
      H. pylori infection has no effect on gastric wall thickness.

PMID- 18814136
TI  - MRI findings in parosteal osteosarcoma: correlation with histopathology.
AB  - PURPOSE: To assess the role of magnetic resonance imaging (MRI), particularly
      signal intensity changes, in predicting the dedifferentiation of parosteal
      osteosarcoma, and to evaluate other factors that may affect grading on MRI.
      MATERIALS AND METHODS: MRI of 12 patients with parosteal osteosarcoma diagnosed
      on plain radiography were reviewed with regard to size, location, extent, soft
      tissue component, intramedullary invasion, and signal characteristics. The
      findings are correlated with histopathologic results. RESULTS: By
      histopathological examination there were 6 Grade I, 3 Grade II, and 3 Grade III
      tumors. Average size was 11 cm. All cases had a soft tissue component.
      Intramedullary extension was evident in 3/6 of the Grade I cases, 2/3 of the
      Grade II cases, and all (3/3) of the Grade III cases. T1-weighted images revealed
      lesions of marked hypointensity. Signal intensity on T2-weighted images varied
      with the presence of necrosis and hemorrhage in relation to size, regardless of
      the grade of the tumor. Contrast-enhanced images revealed enhancement of the
      solid components; no enhancement was observed in the necrotic or hemorrhagic
      parts. CONCLUSION: High and heterogeneous signal on T2-weighted images of Grade
      I, II, and III tumors is not specific for the dedifferentiated component, due to
      hemorrhage and necrosis in large masses. Therefore, high signal intensity on T2
      weighted images is not always a reliable way to predict the grade of the tumor.
      Contrast enhanced T1-weighted images can be valuable to show the solid component
      in the heterogeneous areas on T2-weighted images, and can be useful in guiding
      the biopsy.

PMID- 18814137
TI  - Abernethy malformation with portal vein aneurysm.
AB  - We present the case of a 24-year-old man who was incidentally diagnosed with
      congenital extrahepatic portosystemic shunt with portal vein aneurysm during an
      investigation for non-specific abdominal pain. These are rare anomalies, and to
      the best of our knowledge, this is the first case reported with both anomalies
      associated together. Ultrasound, including color Doppler, computed tomography,
      and magnetic resonance imaging were performed which revealed a side-to-side shunt
      between the extrahepatic portal vein and the inferior vena cava, with aneurysmal
      fusiform dilatation of the proximal intrahepatic portal vein which ended
      abruptly. Etiology, clinical significance, and management strategies with regard
      to these abnormalities are discussed.

PMID- 18814138
TI  - Accuracy of MR coronary angiography in the evaluation of coronary artery
      stenosis.
AB  - PURPOSE: To examine the accuracy of magnetic resonance (MR) coronary angiography
      for the evaluation of coronary artery stenoses, and to compare the results with
      conventional angiography as the reference standard. MATERIALS AND METHODS:
      Eighteen patients were examined. The pulse sequence was an ECG-triggered, T2
      prepared, fat-suppressed 3D true fast imaging with steady state precession
      sequence with navigator respiratory gating. No contrast material was used. The 3D
      slabs were oriented axially, covering the whole heart. The MR images were
      evaluated for the presence of stenoses exceeding 50% luminal narrowing. The
      diagnostic accuracy of MR angiography was calculated, and was compared with
      conventional coronary angiography. All patients gave informed consent, and the
      study was approved by the institutional ethics committee. RESULTS: In
      conventional angiography, 16 stenoses were detected in 11 patients, and 7
      patients were normal. The sensitivity, specificity, positive predictive value
      (PPV), negative predictive value (NPV), and accuracy of MR coronary angiography
      for detecting coronary stenosis on segment-based analysis were 75%, 98%, 80%,
      97%, and 96%, respectively. McNemar test demonstrated no significant difference
      between MR and conventional angiography (P = 0.62). CONCLUSION: MR coronary
      angiography is a non-invasive diagnostic method currently in a state of
      evolution. It has limitations, but can be regarded as an alternative noninvasive
      modality to detect coronary artery disease in selected patient in whom invasive
      angiography may be hazardous.

PMID- 18814139
TI  - Angiographic signs in specific vasculitides.
AB  - Vasculitis, defined by inflammation in the blood vessel wall and reactive mural
      damage, may present with various clinical signs, depending on the organs
      involved. Infection, collagen vascular disease, and granulomatous disease or
      idiopathic inflammation of the vessels may result in various degrees of stenosis,
      obstruction, aneurysmal dilatation, or rupture. The definitive pathologic
      diagnosis is established by biopsy; however, the biopsy may pose significant risk
      to the patient; and the biopsy sample may not be adequate. Knowledge of the
      angiographic signs of various vasculitides should help in interpreting the
      clinical picture and reducing the need for biopsy. In this article, we describe
      the angiographic signs of the most common vasculitides, and review their clinical
      signs.

PMID- 18814140
TI  - Congenital anomalies of the aorta and vena cava: 16-detector-row CT imaging
      findings.
AB  - Cardiovascular specialists should be aware of the common types of congenital
      vascular anomalies and understand their implications for the patient's treatment
      and the likelihood of associated morbidity. Conventional angiography, the gold
      standard in vascular imaging, is an invasive and expensive method. Therefore, in
      recent years, less invasive techniques such as computed tomography angiography
      (CTA) and magnetic resonance angiography have become more widely used. Because of
      the recent advances in CT technology, multi-detector CTA has replaced
      conventional angiography in most clinical applications. Multi-detector CTA is a
      relatively new method and is very useful in the diagnosis and management of
      congenital aorta and vena cava anomalies. This study presents the radiological
      images of congenital anomalies of the aorta and vena cava, obtained through multi
      detector CTA.

PMID- 18814141
TI  - Platelet-derived growth factor stimulates osteoprotegerin production in
      osteoblastic cells.
AB  - Osteoprotegerin (OPG) is a major regulator of osteoclastogenesis, bone resorption
      and vascular calcification. OPG is produced by various cell types including
      mesenchymally derived cells, in particular, osteoblastic cells. Here we show OPG
      production by osteoblastic cells was stimulated by platelet-derived growth factor
      (PDGF) in two human osteosarcoma cell lines (MG63, Saos-2), a mouse pre
      osteoblastic cell line (MC3T3-E1) and human bone marrow stromal cells (hMSC) by
      152%, 197%, 113% and 45% respectively over 24 h. OPG was measured in the cell
      culture medium by immunoassay. PDGF isoforms AA, BB and AB show similar
      stimulation of OPG production. Message for OPG was also increased similarly to
      the increased secretion into the culture medium. Using specific inhibitors of
      cell signalling we demonstrate that PDGF acts through the PDGF receptor, PKC,
      PI3K, ERK and P38 and not via NF-kB or JNK. The importance of PDGF in fracture
      healing suggests a role for OPG production in countering bone resorption during
      the early phase of this process.

PMID- 18814142
TI  - Functional expression of beta2 adrenergic receptors responsible for protection
      against oxidative stress through promotion of glutathione synthesis after Nrf2
      upregulation in undifferentiated mesenchymal C3H10T1/2 stem cells.
AB  - Adrenaline is believed to play a dual role as a neurotransmitter in the central
      nervous system and an adrenomedullary hormone in the peripheral tissues. In
      contrast to accumulating evidence for the involvement in endochondral
      ossification, osteoblastogenesis, and osteoclastogenesis, little attention has
      been paid to the role of adrenergic signals in the mechanisms underlying
      proliferation and differentiation of mesenchymal stem cells with self-renewal
      capacity and multi-potentiality to differentiate into osteoblast, chondrocyte,
      adipocyte, and myocyte lineages. Expression of mRNA was seen for different
      adrenergic receptor (AdR) subtypes, including beta(2)AdR, in the mesenchymal stem
      cell line C3H10T1/2 cells and mouse bone marrow mesenchymal stem cells before
      differentiation. Exposure to adrenaline not only increased cAMP formation,
      phosphorylation of cAMP responsive element (CRE) binding protein (CREB) on
      serine133 and CRE reporter activity in a manner sensitive to propranolol, but
      also rendered C3H10T1/2 cells resistant to the cytotoxicity of hydrogen peroxide,
      but not of either 2,4-dinitirophenol or tunicamycin. Adrenaline induced a rapid
      but transient increase in mRNA expression of the antioxidative gene nuclear
      factor E2 p45-related factor-2 (Nrf2) along with an increase in the
      cystine/glutamate antiporter subunit xCT mRNA expression. Hydrogen peroxide was
      less cytotoxic in cells overexpressing Nrf2, moreover, while adrenaline
      significantly increased xCT promoter activity with an increase in endogenous
      glutathione levels. These results suggest that adrenaline may selectively protect
      mesenchymal C3H10T1/2 cells from oxidative stress through a mechanism related to
      the promoted biosynthesis of glutathione in association with transient Nrf2
      expression after activation of beta(2)AdR.

PMID- 18814143
TI  - Stromal cell-derived factor-1 increase alphavbeta3 integrin expression and
      invasion in human chondrosarcoma cells.
AB  - Chondrosarcoma is a type of highly malignant tumor with a potent capacity to
      invade locally and cause distant metastasis. Chondrosarcoma shows a predilection
      for metastasis to the lungs. The stromal cell-derived factor 1 (SDF-1),
      constitutively secreted by human lung epithelium cells, has been shown to
      function in a key role for recruitment of neutrophils. Here, we found that human
      chondrosarcoma tissues and chondrosarcoma cell lines had significant expression
      of CXCR4 (SDF-1 receptor), which was higher than normal cartilage and human
      chondrocyte. SDF-1alpha and lung epithelium cells conditioned medium (LECM)
      induced the invasiveness of chondrosarcoma cells. SDF-1 siRNA inhibited LECM
      induced invasion of chondrosarcoma cells and SDF-1alpha also directly induced the
      cell surface expression of alphavbeta3 but not alpha2beta1 and alpha5beta1
      integrin. Activations of ERK and NF-kappaB pathways after SDF-1 treatment was
      demonstrated, and SDF-1alpha-induced expression of alphavbeta3 integrin and
      invasion activity was inhibited by the specific inhibitor and mutant of ERK and
      NF-kappaB cascades. Taken together, our results indicate that lung derived-SDF
      1alpha enhances the invasiveness of chondrosarcoma cells by increasing
      alphavbeta3 integrin expression through the CXCR4/ERK/NF-kappaB signal
      transduction pathway.

PMID- 18814144
TI  - Modulation of mouse RANKL gene expression by Runx2 and vitamin D3.
AB  - The expression of receptor activator of nuclear factor-kappaB ligand (RANKL) is
      regulated by bone-seeking hormones such as PTH and 1alpha,25-dihydroxyvitamin D3
      (1,25(OH)2D3). Runx2, a master gene for osteoblastic differentiation, also
      modulates osteoclastogenesis by regulating the RANKL gene. To elucidate the
      mechanism whereby runx2 and 1,25(OH)2D3 regulate RANKL expression, we studied the
      function of runx2 on the chromatin structure and on the proximal binding sites
      using osteoblastic cell lines derived from normal (ST2) and runx2-deficient mice
      (RD-C6). Although the expression of RANKL in the steady-state was higher in RD-C6
      than in ST2, 1,25(OH)2D3-treatment of the cells increased it 20-fold in ST2 but
      only 1.8-fold in RD-C6. Transient transfection studies with proximal RANKL 2kb
      promoter, runx2 knock-down in ST2, and forced expression of runx2 in RD-C6 all
      confirmed that runx2 set the steady-state expression of the RANKL gene at a low
      level, but exerted a positive effect on enhanced transcriptional activity in
      response to 1,25(OH)2D3. Also, assessment of the acetylation status of the area
      spanning 40 kb upstream of the basic promoter in ST2 and RD-C6 by ChIP assay
      revealed that whereas H3 and H4 histone acetylation was detected even in the
      steady-state in RD-C6, it was detected only with 1,25(OH)2D3 in ST2. In the
      steady-state, runx2 may suppress RANKL gene by condensing the chromatin
      structure; however, it exerts a positive effect on 1,25(OH)2D3-induced RANKL
      transcription when the proximal runx2 sites are accessible. Thus, RANKL
      expression in stromal/osteoblastic cells is keenly regulated by 1,25(OH)2D3 which
      transactivates the gene at two different levels

PMID- 18814145
TI  - Cross-regulation between distinct natural killer T cell subsets influences immune
      response to self and foreign antigens.
AB  - Natural killer T (NKT) cells generally recognize lipid-antigens presented in the
      context of the MHC class I-like molecule CD1d. CD1d-restricted NKT cells consist
      of two broad subsets: Type I, which express an invariant T cell receptor (TCR)
      and type II, which utilize diverse TCR gene segments. A major type II NKT subset
      has been shown to recognize a self-glycolipid, sulfatide. Both subsets play
      important roles in autoimmune diseases, tumor surveillance, and infectious
      diseases. While type I NKT cells protect from tumor growth by enhancing tumor
      surveillance, type II NKT cells may suppress anti-tumor immune responses. In a
      murine autoimmune hepatitis model, type I NKT cells contribute to pathogenesis,
      whereas activation of sulfatide-reactive type II NKT cells protects from disease.
      Sulfatide-mediated activation of type II NKT cells results in modification of
      dendritic cells and induction of anergy in type I NKT cells. Elucidation of this
      novel pathway of cross-regulation among NKT cell subsets will provide tools for
      intervention in autoimmune diseases and for designing strategies for effective
      anti-tumor immunity.

PMID- 18814146
TI  - Gene profiling and pathway analysis of neuroendocrine transdifferentiated
      prostate cancer cells.
AB  - BACKGROUND: Neuroendocrine (NE) cells are present in both normal prostate and
      prostate cancer. In addition, NE differentiation can be induced by various
      factors, such as IL-6, in vitro and in vivo. However, the mechanism of this
      differentiation and the role of NE cells in prostate cancer are not well
      understood. In this study, we evaluated the gene expression and analyzed the
      pathways in prostate cancer cells exposed to various NE differentiation inducing
      factors in vitro. METHODS: Gene expression signatures between control LNCaP cells
      and each treatment induced NE cell line were compared using Affymetrix GeneChip
      with network and pathway analysis. RESULTS: All treatments were able to
      transdifferentiate LNCaP cells into NE phenotype as shown by morphology changes
      and NE marker measurements. Of the 54,675 oligonucleotide-based probe sets in
      microarray, 44,975 were mapped into the Ingenuity Pathway Analysis database and
      were filtered according to the t-test P value. At P < 0.002, the number of genes
      that were differentially expressed included 302 of the IL-6 treated cells, 201 of
      genistein, 233 of epinephrine, and 191 of the charcoal stripped serum ones. A
      pooled data approach also showed 346 differentially expressed genes at the same P
      value. Gene ontology analysis showed that cancer-related function had the highest
      significance. CONCLUSIONS: Despite some overlap, each NE transdifferentiation
      inducing treatment was associated with a changed expression of a unique set of
      genes, and such gene profiling may help to elucidate the molecular mechanisms
      involved in NE transdifferentiation of prostate cancer cells.

PMID- 18814147
TI  - Photoelectrochemistry with ordered CdS nanoparticle/relay or
      photosensitizer/relay dyads on DNA scaffolds.

PMID- 18814148
TI  - An immobilization method of chiral quaternary ammonium salts onto polymer
      supports.

PMID- 18814149
TI  - Self-propelled oil droplets on metal surfaces during electrodeposition.

PMID- 18814150
TI  - Binding of DNA nucleobases and nucleosides with graphene.
AB  - Interaction of two different samples of graphene with DNA nucleobases and
      nucleosides is investigated by isothermal titration calorimetry. The relative
      interaction energies of the nucleobases decrease in the order guanine (G)>adenine
      (A)>cytosine (C)>thymine (T) in aqueous solutions, although the positions of C
      and T seem to be interchangeable. The same trend is found with the nucleosides.
      Interaction energies of the A-T and G-C pairs are somewhere between those of the
      constituent bases. Theoretical calculations including van der Waals interaction
      and solvation energies give the trend G>A approximately T>C. The magnitudes of
      the interaction energies of the nucleobases with graphene are similar to those
      found with single-walled carbon nanotubes.

PMID- 18814151
TI  - Shape development and structure of a complex (otoconia-like?) calcite-gelatine
      composite.

PMID- 18814152
TI  - Si@Al56[N(2,6-iPr2C6H3)SiMe3]12: the largest neutral metalloid aluminum cluster,
      a molecular model for a silicon-poor aluminum-silicon alloy?

PMID- 18814154
TI  - A proton-conducting fuel cell operating with hydrocarbon fuels.

PMID- 18814153
TI  - Tip-enhanced near-field optical microscopy.
AB  - Spectroscopic methods with high spatial resolution are essential for
      understanding the physical and chemical properties of nanoscale materials,
      including quantum structures and biological surfaces. An optical technique is
      reviewed that relies on the enhanced electric fields in the proximity of a sharp,
      laser-irradiated metal tip. These fields are utilized for spatially confined
      probing of various optical signals, thus allowing for a detailed sample
      characterization far below the diffraction limit. In addition, tip-enhanced
      fields also provide the sensitivity crucial for the detection of nanoscale
      volumes. After outlining the principles of near-field optics, the mechanisms
      contributing to local field enhancement and how it can be used to enhance optical
      signals are discussed. Different experimental methods are presented and several
      recent examples of Raman and fluorescence microscopy with 10 nm spatial
      resolution of single molecules are reviewed.

PMID- 18814155
TI  - It all began with an error: the nomofungin/communesin story.
AB  - The communesin/nomofungin/perophoramidine story is an impressive example of how
      biogenetic considerations can lead to the correction of structural misassignments
      and inspire synthetic chemists with new, fruitful ideas. Intensive studies by a
      number of research groups culminated in the total synthesis of perophoramidine by
      the Funk research group in 2004. In 2007, Qin and co-workers completed the first
      total synthesis of a communesin.

PMID- 18814156
TI  - Ruthenium-catalyzed cycloaddition of nitrile oxides and alkynes: practical
      synthesis of isoxazoles.

PMID- 18814157
TI  - Postsynthetic DNA modification through the copper-catalyzed azide-alkyne
      cycloaddition reaction.
AB  - The attachment of labels onto DNA is of utmost importance in many areas of
      biomedical research and is valuable in the construction of DNA-based functional
      nanomaterials. The copper(I)-catalyzed Huisgen cycloaddition of azides and
      alkynes (CuAAC) has recently been added to the repertoire of DNA labeling
      methods, thus allowing the virtually unlimited functionalization of both small
      synthetic oligonucleotides and large gene fragments with unprecedented
      efficiency. The CuAAC reaction yields the labeled polynucleotides in very high
      purity after a simple precipitation step. The reviewed technology is currently
      changing the way in which functionalized DNA strands are generated cost
      efficiently in high quality for their application in molecular diagnostics
      systems and nanotechnological research.

PMID- 18814158
TI  - Semisynthesis of a glycosylphosphatidylinositol-anchored prion protein.

PMID- 18814159
TI  - High internal phase emulsions stabilized solely by functionalized silica
      particles.

PMID- 18814160
TI  - Cooperativity between the halogen bond and the hydrogen bond in H3N...XY...HF
      complexes (X, Y=F, Cl, Br).
AB  - Ab initio calculations are used to provide information on H(3)N...XY...HF triads
      (X, Y=F, Cl, Br) each having a halogen bond and a hydrogen bond. The investigated
      triads include H(3)N...Br(2)-HF, H(3)N...Cl(2)...HF, H(3)N...BrCl...HF,
      H(3)N...BrF...HF, and H(3)N...ClF...HF. To understand the properties of the
      systems better, the corresponding dyads are also investigated. Molecular
      geometries, binding energies, and infrared spectra of monomers, dyads, and triads
      are studied at the MP2 level of theory with the 6-311++G(d,p) basis set. Because
      the primary aim of this study is to examine cooperative effects, particular
      attention is given to parameters such as cooperative energies, many-body
      interaction energies, and cooperativity factors. The cooperative energy ranges
      from -1.45 to -4.64 kcal mol(-1), the three-body interaction energy from -2.17 to
      -6.71 kcal mol(-1), and the cooperativity factor from 1.27 to 4.35. These results
      indicate significant cooperativity between the halogen and hydrogen bonds in
      these complexes. This cooperativity is much greater than that between hydrogen
      bonds. The effect of a halogen bond on a hydrogen bond is more pronounced than
      that of a hydrogen bond on a halogen bond.

PMID- 18814161
TI  - New insight into the properties of proton-conducting oxides from neutron total
      scattering.

PMID- 18814162
TI  - Sensing on a molecular level--chemistry at the interface of information
      technology.

PMID- 18814163
TI  - Colossal pressure-induced lattice expansion of graphite oxide in the presence of
      water.

PMID- 18814164
TI  - Depolymerization of cellulose using solid catalysts in ionic liquids.

PMID- 18814165
TI  - Catalytic enantioselective Michael addition of 1-fluorobis(phenylsulfonyl)methane
      to alpha,beta-unsaturated ketones catalyzed by cinchona alkaloids.

PMID- 18814166
TI  - Catalytic asymmetric hydroperoxidation of alpha,beta-unsaturated ketones: an
      approach to enantiopure peroxyhemiketals, epoxides, and aldols.

PMID- 18814167
TI  - Copper-catalyzed asymmetric conjugate addition of aryl aluminum reagents to
      trisubstituted enones: construction of aryl-substituted quaternary centers.

PMID- 18814168
TI  - Asymmetric cross-coupling of non-activated secondary alkyl halides.

PMID- 18814169
TI  - Experimental and theoretical study of helium broadening and shift of HCO+
      rotational lines.
AB  - An experimental and theoretical study of pressure broadening and pressure shift
      of HCO(+) rotational lines perturbed by collisions with He is presented. Results
      are reported from measurements at 88 K for the lines j=4<--3, 5<--4 and 6<--5
      with frequencies ranging from 0.35 to 0.54 THz. Using a new CCSD(T)/aug-cc-pVQZ
      potential energy surface for the He-HCO(+) interaction, the collisional line
      shape parameters are studied from fully quantum and semiclassical calculations.
      Results from the quantum treatment are in satisfactory agreement with experiments
      whereas the semiclassical approach can lead to appreciable differences. A study
      of the dependence of line width Gamma and shift s as a function of the
      translational energy shows the presence of quantum oscillations. Calculations on
      a previous Hartree-Fock-based potential energy surface lead to quite similar
      results for the collisional line shape parameters. Using a simplified version of
      the potential morphing method it is found that the line width Gamma is
      particularly sensitive to the long-range part of the potential energy surface.
      This also explains the success of the first line-broadening calculations which
      date back to the 1950s.

PMID- 18814170
TI  - Towards a quantitative understanding of protein hydration and volumetric
      properties.
AB  - Herein, we probe by pressure perturbation calorimetry (PPC) the coefficient of
      thermal expansion, the volumetric and the hydration properties of variants of a
      hyperstable variant of staphylococcal nuclease (SNase), Delta+PHS. The
      temperature-dependent volumetric properties of the folded and unfolded states of
      the wild-type protein are calculated with previously published data. The present
      PPC results are used to interpret the volume diagram and expansivity at a
      molecular level. We conclude that the expansivity of the unfolded state is, to a
      first approximation, temperature independent, while that of the folded state
      decreases with increasing temperature. Our data suggest that at low temperature
      the defining contribution to DeltaV comes mainly from excluded volume differences
      and DeltaV for unfolding is negative. In contrast, at high temperatures,
      differential solvation due to the increased exposed surface area of the unfolded
      state and, in particular, its larger thermal volume linked to the increased
      conformational dynamics of the unfolded state ensemble takes over and DeltaV for
      unfolding eventually becomes positive.

PMID- 18814171
TI  - Fluoride binding in water: a new environment for a known receptor.

PMID- 18814172
TI  - SERS and multiphoton-induced luminescence of gold micro- and nanostructures
      fabricated by NIR femtosecond-laser irradiation.

PMID- 18814173
TI  - Self-assembly of peptide-based colloids containing lipophilic nanocrystals.

PMID- 18814174
TI  - Multiplexed lipid dip-pen nanolithography on subcellular scales for the
      templating of functional proteins and cell culture.
AB  - Molecular patterning processes taking place in biological systems are challenging
      to study in vivo because of their dynamic behavior, subcellular size, and high
      degree of complexity. In vitro patterning of biomolecules using nanolithography
      allows simplification of the processes and detailed study of the dynamic
      interactions. Parallel dip-pen nanolithography (DPN) is uniquely capable of
      integrating functional biomolecules on subcellular length scales due to its
      constructive nature, high resolution, and high throughput. Phospholipids are
      particularly well suited as inks for DPN since a variety of different functional
      lipids can be readily patterned in parallel. Here DPN is used to spatially
      pattern multicomponent micro- and nanostructured supported lipid membranes and
      multilayers that are fluid and contain various amounts of biotin and/or
      nitrilotriacetic acid functional groups. The patterns are characterized by
      fluorescence microscopy and photoemission electron microscopy. Selective
      adsorption of functionalized or recombinant proteins based on streptavidin or
      histidine-tag coupling enables the semisynthetic fabrication of model peripheral
      membrane bound proteins. The biomimetic membrane patterns formed in this way are
      then used as substrates for cell culture, as demonstrated by the selective
      adhesion and activation of T-cells.

PMID- 18814178
TI  - High frequency of prostate antigen-directed T cells in cancer patients compared
      to healthy age-matched individuals.
AB  - BACKGROUND: In order to obtain a sustained cytotoxic T lymphocyte (CTL) response
      against cancer cells it is preferable to have CTLs directed against multiple
      peptide epitopes from numerous tumor-associated antigens. METHODS: We used a Flow
      Cytometry-based interferon (IFN)-gamma secretion assay with peptide-pulsed C1R-A2
      as antigen-presenting cells to analyze whether CD8+ T cells directed against any
      of 24 HLA-A*0201-binding peptides from 15 prostate-associated proteins can be
      found in the peripheral blood of patients with localized prostate cancer. We also
      investigated whether multiple prostate antigen-specific CD8+ T cells can be
      generated simultaneously, from a naive T cell repertoire. In that case, dendritic
      cells (DCs) from peripheral blood of healthy donors were divided in six portions
      and separately pulsed with six peptides. The peptide-pulsed DCs were then pooled
      and used to stimulate autologous T cells. The T cells were re-stimulated with
      peptide-pulsed monocytes. RESULTS: We found prostate antigen-restricted CD8+ T
      cells in the peripheral blood in 48 out of 184 (26.1%) analyzed samples from 25
      cancer patients. This is significantly higher than 17 out of 214 analyzed samples
      (7.9%) from 10 healthy age-matched male individuals (P = 0.0249). In the cases
      when antigen-specific T cells could not be detected, we were able to generate IFN
      gamma-producing CD8+ T cells specific for up to three prostate antigens
      simultaneously from a naive T cell repertoire. CONCLUSIONS: CD8+ T cells directed
      against prostate antigen peptides can be found in, or generated from, peripheral
      blood. This indicates that such T cells could be expanded ex vivo for adoptive
      transfer to prostate cancer patients.

PMID- 18814177
TI  - CB1 cannabinoid receptor-dependent and -independent inhibition of depolarization
      induced calcium influx in oligodendrocytes.
AB  - Regulation of Ca(2+) homeostasis plays a critical role in oligodendrocyte
      function and survival. Cannabinoid CB(1) and CB(2) receptors have been shown to
      regulate Ca(2+) levels and/or K(+) currents in a variety of cell types. In this
      study we investigated the effect of cannabinoid compounds on the Ca(2+) influx
      elicited in cultured oligodendrocytes by transient membrane depolarization with
      an elevated extracellular K(+) concentration (50 mM). The CB(1) receptor agonist
      arachidonoyl-chloro-ethanolamide (ACEA) elicited a concentration-dependent
      inhibition of depolarization-evoked Ca(2+) transients in oligodendroglial somata
      with a maximal effect (94+/-3)% and an EC(50) of 1.3+/-0.03 microM. This activity
      was mimicked by the CB(1)/CB(2) agonist CP55,940, as well as by the
      endocannabinoids N-arachidonoyl-ethanolamine (anandamide, AEA) and 2
      arachidonoylglycerol (2-AG), whereas the CB(2) receptor selective agonist JWH133
      was ineffective. The CB(1) receptor antagonist AM251 (1 microM) also reduced the
      Ca(2+) response evoked by high extracellular K(+) and did not prevent the
      inhibition elicited by ACEA (3 microM). Nevertheless, the ability of ACEA and AEA
      to reduce depolarization-evoked Ca(2+) transients was significantly reduced in
      oligodendrocytes from CB(1) receptor knockout mice, as well as by pretreatment
      with pertussis toxin. Bath application of the inwardly rectifying K(+) channels
      (Kir channels) blockers BaCl(2) (300 microM) and CsCl(2) (1 mM) reduced the size
      of voltage-induced Ca(2+) influx and partially prevented the inhibitory effect of
      ACEA. Our results indicate that cannabinoids inhibit depolarization-evoked Ca(2+)
      transients in oligodendrocytes via CB(1) receptor-independent and -dependent
      mechanisms that involve the activation of PTX-sensitive G(i/o) proteins and the
      blockade of Kir channels.

PMID- 18814179
TI  - The EphA3 receptor is expressed in a subset of rhabdomyosarcoma cell lines and
      suppresses cell adhesion and migration.
AB  - Elevated expression of the Eph receptor tyrosine kinase EphA3 is associated with
      lymphocytic leukaemia, but little is known about its expression or function in
      solid tumours. Out of a panel of cancer cell lines, we found that EphA3 was
      expressed only on two rhabdomyosarcoma (RMS) cell lines of the embryonal
      histological subtype and on one of the alveolar RMS subtype, whereas it was not
      detected on two other cell lines of the alveolar subtype. Other EphA receptors (1
      7) were, either not expressed in any, or expressed in all five RMS cell lines.
      Stimulation of EphA3-expressing TE671 and RD RMS cells with ephrinA5 resulted in
      loss of adhesion to fibronectin, decreased migration towards the stromal cell
      derived growth factor-I (SDF-I), increased EphA3 phosphorylation, and increased
      Rho GTPase activity. In contrast, ectopic expression of EphA3 in the EphA3
      negative CRL2061 cell line resulted in decreased cell adhesion. Finally,
      suppression of EphA3 expression by siRNA in RD cells results in increased SDF-I
      mediated motility. These data indicate that EphA3 expression may define subsets
      of RMS tumours, and that EphA3 suppresses motility through regulation of Rho
      GTPases in RMS cells.

PMID- 18814180
TI  - Elk-1, CREB, and MKP-1 regulate Egr-1 expression in gonadotropin-releasing
      hormone stimulated gonadotrophs.
AB  - Stimulation of gonadotropin-releasing hormone (GnRH) receptors with the GnRH
      analogue buserelin enhances expression of the zinc finger transcription factor
      Egr-1 in a pituitary gonadotroph cell line. The signaling cascade is blocked by
      overexpression of MAP kinase phosphatase-1 that dephosphorylates extracellular
      signal-regulated protein kinase in the nucleus. Chromatin immunoprecipitation
      experiments revealed that the phosphorylated form of Elk-1, a key regulator of
      gene transcription driven by serum response element (SRE), binds to the 5'
      upstream region of the Egr-1 gene in buserelin-stimulated gonadotrophs.
      Expression of a dominant-negative mutant of Elk-1 completely blocked Egr-1
      expression, indicating that Elk-1 connects the intracellular signaling cascade
      elicited by activation of GnRH receptors with transcription of the Egr-1 gene.
      GnRH receptor activation additionally induced the phosphorylation of CREB, which
      in its phosphorylated form bound to the Egr-1 gene. Expression of a dominant
      negative mutant of CREB reduced GnRH receptor-induced upregulation of Egr-1
      expression, indicating that CREB plays a role in the signaling pathway that
      regulates Egr-1 expression in gonadotrophs. We further identified the genes
      encoding basic fibroblast growth factor, tumor necrosis factor alpha, and
      transforming growth factor beta as bona fide target genes of Egr-1 in
      gonadotrophs. The analysis of gonadotroph cells that express--in addition to GnRH
      receptors--muscarinic M(3) acetylcholine receptors revealed that the nuclear
      events connecting GnRH receptors and muscarinic M(3) acetylcholine receptors with
      the Egr-1 gene are indistinguishable.

PMID- 18814181
TI  - Catalytically inactive SHIP2 inhibits proliferation by attenuating PDGF signaling
      in 3T3-L1 preadipocytes.
AB  - Inadequate proliferation and/or differentiation of preadipocytes may lead to
      adipose tissue dysfunction characterized by hypertrophied, insulin-resistant
      adipocytes. Platelet-derived growth factor (PDGF) may alter adipose tissue
      function by promoting proliferation of preadipocytes. Two principal signaling
      pathways that regulate proliferation are PI3K/PI(3,4,5)P3/Akt and Shc/Ras/ERK1/2.
      SH2 domain-containing inositol 5-phosphatase 2 (SHIP2) dephosphorylates
      PI(3,4,5)P3, and also binds to Shc. Our goal was to determine how SHIP2 affects
      these PDGF signaling routes. To assess the role of the 5-phosphatase domain, we
      expressed wild-type or catalytically inactive dominant-negative SHIP2 (P686A
      D690A-R691A; PDR/AAA) in 3T3-L1 preadipocytes. Surprisingly, SHIP2 PDR/AAA
      inhibited proliferation more potently than wild-type SHIP2. After three days of
      proliferation, phospho-Akt, phospho-ERK1/2, and PDGF receptor (PDGFR) levels were
      reduced in PDR/AAA-expressing preadipocytes. SHIP2 PDR/AAA interference with
      PDGFR signaling was demonstrated using imatinib, an inhibitor of PDGFR tyrosine
      kinase. The anti-proliferative effect of imatinib observed in control
      preadipocytes was not significant in SHIP2 PDR/AAA-expressing preadipocytes,
      indicating a pre-existing impairment of PDGFR-dependent mitogenesis in these
      cells. The inhibition of PDGF-activated mitogenic pathways by SHIP2 PDR/AAA was
      consistent with a decrease in PDGFR phosphorylation caused by a drop in receptor
      levels in SHIP2 PDR/AAA-expressing cells. SHIP2 PDR/AAA promoted ubiquitination
      of the PDGFR and its degradation via the lysosomal pathway independently of the
      association between the E3 ubiquitin ligase c-Cbl and PDGFR. Overall, our
      findings indicate that SHIP2 PDR/AAA reduces preadipocyte proliferation by
      attenuating PDGFR signaling.

PMID- 18814182
TI  - Predicting cardiac vagal regulation in early childhood from maternal-child
      relationship quality during toddlerhood.
AB  - The aim of this study was to examine the influence of maternal-child relationship
      quality during toddlerhood on early childhood physiological regulation. A
      community sample of 447 children (215 males) was recruited at age 2 for
      participation in the study using the Child Behavior Checklist [Achenbach [1992]
      Manual for the child behavior checklist/2-3 & 1992 profile. Burlington, VT:
      University of VT Department of Psychiatry]. Mothers and children were observed
      across several interactions in the laboratory at age 2 and mothers completed the
      Parenting Stress Index [Abidin [1995] Manual for the parenting stress index.
      Odessa, FL: Psychological Assessment Resources]. Relationship quality was
      assessed using laboratory measures of hostility, positive guidance, and stress
      related to the quality of the relationship as reported by mothers. Cardiac vagal
      regulation at age 2 was assessed across six challenge tasks, three in which the
      child and mother worked together and three in which the child worked
      independently, and was indexed by the magnitude of vagal withdrawal (decrease in
      respiratory sinus arrhythmia, RSA) to challenge. Results indicated that children
      displayed greater cardiac vagal regulation and heart rate acceleration during
      collaborative tasks versus independent tasks. In addition, maternal-child
      relationship quality predicted the degree of vagal regulation in children at age
      5, even after controlling for early and concurrent level of behavior problems as
      well as 2-year cardiac vagal regulation. Children with poorer quality
      relationships displayed significantly poorer vagal regulation and lower heart
      rate acceleration (p < .01). These findings are discussed in terms of the
      implications of environmental factors for the acquisition of fundamental self
      regulatory skills.

PMID- 18814183
TI  - Iron deficiency anemia and affective response in rhesus monkey infants.
AB  - Infant iron deficiency anemia (IDA) occurs spontaneously in monkey populations as
      it does in humans, providing a model for understanding effects on brain and
      behavior. A set of 34 monkey infants identified as IDA (hemoglobin <11 g/dl) over
      a 5-year period at the California National Primate Research Center (CNPRC) was
      compared to a set of 57 controls (hemoglobin >12 g/dl) matched for age and caging
      location. The infants had participated in a Biobehavioral Assessment conducted at
      3-4 months of age at CNPRC that included measures of behavioral and
      adrenocortical response to a novel environment. IDA males differed from control
      males in two factors ("activity," "emotionality") derived from observational data
      taken on the first and second day of the exposure to the novel environment. In
      the male infants, IDA was associated with less restriction of activity in the
      novel environment on both days and less emotionality on the second day (p < .05).
      IDA males also displayed less response to approach by a human (human intruder
      test) than did control males. IDA females did not differ from controls.
      Adrenocortical response was not significantly affected. These findings may be
      relevant to functional deficits in human infants with IDA that influence later
      behavior.

PMID- 18814184
TI  - The tyrosine kinase receptor HER2 (erbB-2): from oncogenesis to adipogenesis.
AB  - Recent experimental evidences begin to support the notion that the proto-oncogene
      HER2 (erbB-2) might unexpectedly function to modulate the adipogenic conversion
      of preadipocytes. Two opposing scenarios have been proposed, however, to explain
      the influence of HER2 on adipocyte differentiation. In one hand, down-modulation
      of HER2 expression and pharmacological reduction of HER2 activity have been
      related to enhanced adipocyte differentiation. On the contrary, an increased
      abundance in HER2 has been described in differentiated adipocytes compared with
      preadipocytes. Considering that expression and activity of the lipogenic enzyme
      Fatty Acid Synthase (FASN) become up-regulated during adipogenic conversion, we
      recently hypothesized that a "HER2 --> FASN axis" -a "lipogenic benefit" that has
      been shown to enhance cancer cell proliferation, survival, chemoresistance and
      metastasis in biologically aggressive subgroups of breast carcinomas-might also
      naturally work during the differentiation of preadipocytes. To definitely clarify
      if the discrepancy between the opposing theories for a role of HER2 during
      adipocyte differentiation related to the experimental approach utilized to
      compare the abundance of HER2 in undifferentiated and differentiated adipocytes
      (i.e., cell lysates containing equivalent protein content versus cell lysates
      generated from similar cell numbers), we here took advantage of a high content
      microscopy approach. Using an automated confocal imaging platform, we monitored
      the expression status of the adipogenic marker FASN and its timing relationship
      with HER2 not only in individual 3T3-L1 cells but further in whole cultures of
      3T3-L1 preadipocytes undergoing adipogenic conversion. Our findings not only
      confirm a non-oncogenic role for HER2 in the process of adipose differentiation
      but further suggest that HER2 might represent a previously unrecognized target to
      manage obesity via the lipogenic enzyme FASN.

PMID- 18814186
TI  - Retraction. Nootropic-like effect of ashwagandha (Withania somnifera L.) in mice.

PMID- 18814185
TI  - Maternal endothelial function and serum concentrations of placental growth factor
      and soluble endoglin in women with abnormal placentation.
AB  - OBJECTIVES: To determine whether maternal serum concentrations of placental
      growth factor (PlGF) and soluble endoglin (sEng) are altered in women who
      subsequently develop pre-eclampsia (PE) or have small-for-gestational-age (SGA)
      infants, and whether these changes are associated with maternal endothelial
      dysfunction. METHODS: Maternal serum PlGF and sEng were measured in two groups of
      pregnant women at 23-25 weeks' gestation: Group A (n = 40), with normal uterine
      artery Doppler waveforms and Group B (n = 43) with abnormal Doppler. Maternal
      endothelial dysfunction was assessed by flow-mediated dilatation (FMD) of the
      brachial artery. Comparisons between groups were performed using one-way analysis
      of variance. RESULTS: In Group B, 16 women had normal outcome, 15 delivered SGA
      infants and 12 developed PE. Women who developed PE had lower levels of PlGF
      (154.8 +/- 150.8 vs. 423.3 +/- 230.5 pg/mL; P < 0.001) (data given as mean +/-
      SD) and higher levels of sEng (8.1 (7.0-14.1) vs. 6.5 (4.9-7.9) pg/mL; P < 0.05)
      (data given as median (interquartile range)) than Group A. Similar were the
      findings in women who delivered SGA infants. In women who subsequently developed
      PE, there was no correlation between FMD and either PlGF or sEng. CONCLUSIONS:
      Maternal serum concentrations of PlGF and sEng are altered in women who develop
      PE. However, these alterations do not correlate directly with maternal
      endothelial dysfunction.

PMID- 18814187
TI  - Study on the interaction between nitroxide free radical and conjugated
      polyelectrolytes by fluorimetry.
AB  - In this work, we studied the fluorescence quenching of the anionic conjugated
      polyelectrolyte PPE-SO(3) by the paramagnetic species 2,2,6,6
      tetramethylpiperidine-N-oxide free radical (TEMPO) in aqueous solution. At low
      quencher concentration the Stern-Volmer constant is 94 mol/L; as the quencher
      concentration increases the Stern-Volmer plots become superlinear. Ascorbic acid
      is used to reduce TEMPO to the corresponding hydroxylamine and the PPE-SO(3)
      fluorescence is fully recovered. Under a large excess of ascorbic acid over
      TEMPO, the rise of fluorescence followed pseudo-first-order kinetics. The second
      order rate constant calculated from this time course is 0.7 mol/L/s.

PMID- 18814188
TI  - A critical evaluation of a flow-cell based on a liquid core waveguide for
      chemiluminescence measurements.
AB  - Liquid-core waveguides (LCWs), devices that constrain the emitted radiation
      minimizing losses during the transport, are an alternative to maximize the amount
      of detected radiation in luminescence. In this work, the performance of a LCW
      flow-cell was critically evaluated for chemiluminescence measurements, by using
      as model the oxidation of luminol by hydrogen peroxide or hypochlorite. An
      analytical procedure for hypochlorite determination was also developed, with
      linear response in the range 0.2-3.8 mg/L (2.7-51 micromol/L), a detection limit
      estimated as 8 microg/L (0.64 micromol/L) at the 99.7% confidence level and
      luminol consumption of 50 microg/determination. The coefficients of variation
      were 3.3% and 1.6% for 0.4 and 1.9 mg/L ClO(-), respectively, with a sampling
      rate of 164 determinations/h. The procedure was applied to the analysis of
      Dakin's solution samples, yielding results in agreement with those obtained by
      iodometric titration at the 95% confidence level.

PMID- 18814189
TI  - Quantum dots light up pathology.
AB  - Quantum dots (QDs) are novel nanocrystal fluorophores with extremely high
      fluorescence efficiency and minimal photobleaching. They also possess a constant
      excitation wavelength together with sharp and symmetrical tunable emission
      spectra. These unique optical properties make them near-perfect fluorescent
      markers and there has recently been rapid development of their use for
      bioimaging. QDs can be conjugated to a wide range of biological targets,
      including proteins, antibodies, and nucleic acid probes, rendering them of
      particular interest to pathology researchers. They have been used in multiplex
      immunohistochemistry and in situ hybridization, which when combined with
      multispectral imaging, has enabled quantitative measurement of gene expression in
      situ. QDs have also been used for live in vivo animal imaging and are now being
      applied to an ever-increasing range of biological problems. These are detailed in
      this review, which also acts to outline the important advances that have been
      made in their range of applications. The relative novelty of QDs can present
      problems in their practical use and guidelines for their application are given.

PMID- 18814190
TI  - Long-term sustained benefits of clozapine treatment in refractory early onset
      schizophrenia: a retrospective study in Korean children and adolescents.
AB  - OBJECTIVE: Treatment resistance in early onset schizophrenia (EOS) is one of the
      most challenging problems in child and adolescent psychiatry. We retrospectively
      examined the therapeutic dosage, clinical response, and side effect profiles of
      long-term clozapine treatment in Korean children and adolescents with refractory
      EOS or very early onset schizophrenia (VEOS). METHOD: 26 refractory patients
      treated with clozapine for more than 1 year were analyzed. Efficacy was
      determined by comparing hospitalization rate and duration, before and after
      clozapine treatment. Tolerability was assessed through review of documented
      adverse events. RESULTS: A significant reduction in hospital days per year was
      observed in 25 (96.2%) patients after clozapine treatment compared to before
      clozapine. Long-term benefit of the treatment was supported by a further
      reduction of the hospitalization rate in 14 patients treated with clozapine for
      more than 3 years. Neutropenia developed in 26.9% patients at 1 year and there
      was no agranulocytosis. Overall, eight male patients (8/12, 66.7%) and one female
      patient (1/14, 7%) developed neutropenia and out of the nine patients, seven
      patients were maintained and two patients were successfully rechallenged on
      clozapine. CONCLUSION: These findings suggest that long-term clozapine treatment
      may effectively reduce the amount of time Asian patients with refractory EOS or
      VEOS spend in the hospital. However careful monitoring of adverse events is
      required.

PMID- 18814191
TI  - Maternal varicella infection during pregnancy in a vaccinated patient.

PMID- 18814192
TI  - Liquid chromatographic method for the determination of sirolimus in blood using
      electrochemical detection.
AB  - Therapeutic drug monitoring of sirolimus (rapamycin) is important for
      immunosuppressive therapy in solid organ transplantation. We have developed a
      simple and reliable method for determining blood concentrations of sirolimus
      using reversed-phase HPLC with electrochemical detection (ECD). The E(2)
      potential was set at +900 mV. The potential of guard cell was set at +950 mV and
      that of the E(1) cell at +400 mV. The method was linear for a concentration range
      of 1-50 ng/mL when 0.5 mL blood was used. The correlation coefficients of all
      standard curves were greater than or equal to 0.999. The limit of detection was
      0.5 ng/mL. The inter-assay precision ranged from 3.22 to 7.48%, and the
      coefficient of variation (CV) for a quality control sample at 10 ng/mL was 7.48%
      with a bias of 8.4% from the target value. The intra-assay precision ranged from
      0.72 to 3.71%, and the CV for a quality control sample at 10 ng/mL was 0.72% with
      a bias of 6.8% from the target value. In a solid organ transplant recipient,
      trough concentrations of sirolimus were well within the analytic range of the
      HPLC/ECD procedure. The method described here is suitable for management of
      sirolimus therapy in solid organ transplantation.

PMID- 18814193
TI  - Development and validation of a sensitive LC-MS/MS method with electrospray
      ionization for quantitation of pramipexole in human plasma: application to a
      clinical pharmacokinetic study.
AB  - A highly sensitive and specific LC-MS/MS method has been developed and validated
      for the estimation of pramipexole (PPX) with 500 microL human plasma using
      memantine as an internal standard (IS). The API-4000 was operated under multiple
      reaction monitoring mode (MRM) using the electrospray ionization technique. Solid
      phase extraction was used to extract PPX and IS from human plasma. The resolution
      of peaks was achieved with 0.01 m ammonium acetate buffer (pH 4.4):acetonitrile
      (30:70, v/v) on a Discovery CN column. The total chromatographic run time was 3.0
      min and the elution of PPX and IS occurred at approximately 2.32 and 2.52,
      respectively. The MS/MS ion transitions monitored were 212.10 --> 153.10 for PPX
      and 180.20 --> 107.30 for IS. The method was proved to be accurate and precise at
      linearity range of 20-3540 pg/mL with a correlation coefficient (r) of > or
      =0.999. The intra- and inter-day precision and accuracy values found to be within
      the assay variability limits as per the FDA guidelines. The developed assay
      method was applied to a pharmacokinetic study in human volunteers following oral
      administration of 0.25 mg PPX tablet.

PMID- 18814194
TI  - Determination of serotonin, melatonin and metabolites in gastrointestinal tissue
      using high-performance liquid chromatography with electrochemical detection.
AB  - In this paper we show a simple isocratic chromatographic method for the detection
      of serotonin and its precursors and metabolites from various types of
      gastrointestinal tissue. The paper measures for the first time basal measurements
      of melatonin in the gastrointestinal tract, which has recently been shown to be
      released from the musosal lining of the gut. Tissue samples were stable following
      sample preparation in either 0.1 m perchloric acid or mobile phase. Analysis was
      carried out using a mobile phase consisting of 10% acetonitrile-90% acetate acid
      buffer pH 4.0 with 2 mm decane-sulfonic acid sodium salt at a column temperature
      of 50 degrees C. Electrochemical detection was utilized at a potential of +850 mV
      vs Ag/AgCl reference electrode at 10 microA full-scale deflection. The detection
      limit of 5-HT and melatonin was 241 and 308 nm respectively for a 10 microL
      injection. As a result of the method optimization, total analysis was reduced to
      30 min. Accurate responses of the tissue samples following sample preparation
      could be obtained following a week after storage at -80 degrees C. This method is
      capable of preparing and analysing of samples from all regions of the
      gastrointestinal tract.

PMID- 18814195
TI  - Separation of flavins and nicotinamide cofactors in Chinese hamster ovary cells
      by capillary electrophoresis.
AB  - Simultaneous extraction, separation and quantitation of reduced nicotinamide
      adenine dinucleotide (NADH), reduced nicotinamide adenine dinucleotide phosphate
      (NADPH), flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN) in
      Chinese Hamster Ovary (CHO) cells were investigated. The separation of flavins
      and nicotinamide cofactors was performed by capillary electrophoresis with laser
      induced fluorescence detection at the excitation wavelength of 325 nm. The
      separation protocol was established by investigating the excitation wavelength,
      high voltage and effects of buffer nature, pH and concentration. All endogenous
      fluorophores riboflavin, FAD, FMN, NADH and NADPH show wide linear range of
      quantitation. The limits of detection for the five compounds ranged from 4.5 to
      23 nM. Extraction conditions were optimized for high-efficiency recovery of all
      endogenous fluorophores from CHO cells. To account for the complex matrix of cell
      extracts, a standard addition method was used to quantify FAD, FMN, NADH and
      NADPH in CHO cells. The quantitative results should be useful to reveal the
      metabolic status of cells. The protocols for extraction, separation and
      quantitation are readily adaptable to normal and cancer cell lines for the
      analysis of endogenous fluorophores.

PMID- 18814196
TI  - Optimizing high-performance liquid chromatography method for quantification of
      glucosamine using 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate derivatization
      in rat plasma: application to a pharmacokinetic study.
AB  - A sensitive and reliable HPLC method with fluorescence detection based on the
      precolumn derivatization of glucosamine with 6-aminoquinolyl-N
      hydroxylsuccinimidyl carbamate (AQC) was established for the quantitative
      determination of glucosamine in rat plasma. The plasma protein was precipitated
      by acetonitrile, followed by vortex mixing and centrifugation. The supernatant
      was divided into the organic layer and aqueous layer by adding sodium chloride,
      and then the aqueous layer was derivatized with AQC in 0.2 M borate buffer of pH
      8.8 before the HPLC analysis. An amino acid analysis column (3.9 x 150 mm, 4
      microm) was applied, with 140 mM sodium acetate buffer (pH = 5.25) and
      acetonitrile as mobile phase at a flow rate of 1 mL/min. A linear correlation
      coefficient of 0.9987 was calculated within the range of 0.1-30 microg/mL of the
      standard curve for glucosamine. The limit of detection was 30 ng/mL. The intra-
      and inter-day precisions (as RSD) were less than 7.38 and 12.72%, respectively.
      The intra- and inter-day accuracy ranged from 91.8 to 110.0%. Extraction
      recoveries of glucosamine in plasma were more than 90%. The validated method was
      successfully applied for the quantitative determination of glucosamine in rat
      plasma and evaluation for pharmacokinetic study of glucosamine. It was also
      possible to be applied for the quantitative determination of other compounds
      containing amino group in biological samples.

PMID- 18814197
TI  - Helping carers to care--the 10/66 dementia research group's randomized control
      trial of a caregiver intervention in Russia.
AB  - OBJECTIVES: Dementia is a rapidly growing public health problem in low and middle
      income countries. There is an urgent need, in the absence of formal services, to
      develop interventions designed to improve the lives of people with dementia, and
      their families. This study tests the effectiveness of the 10/66 caregiver
      intervention among people with dementia, and their carers. DESIGN: A single blind
      parallel group randomized controlled trial (ISRCTN41039907). SETTING: Moscow.
      PARTICIPANTS: Sixty family caregivers of people aged 65 and over with dementia
      were randomized to receive the intervention and medical care as usual (n = 30) or
      medical care as usual only (n = 30). Caregiver and person with dementia outcomes
      were assessed at baseline and after 6 months. INTERVENTION: The caregiver
      education and training intervention was delivered over five, weekly, half-hour
      sessions and was made up of three modules: (i) assessment (one session); (ii)
      basic education about dementia (two sessions); and (iii) training regarding
      specific problem behaviors (two sessions). MEASUREMENTS: Dementia was diagnosed
      using DSM-IV criteria. Caregiver: Zarit Carer Burden Interview; carer
      psychological distress (SRQ 20); and carer Quality of Life (WHOQOL-BREF). Person
      with dementia: Behavioural and Psychological symptoms (NPI-Q); quality of life
      (DEMQOL). RESULTS: Caregivers in the intervention group reported large and
      statistically significant net improvements at 6-month follow-up in burden
      compared to controls. No group differences were found on caregiver psychological
      distress and patient and caregiver quality of life. CONCLUSIONS: The low-level
      intervention seems to be as, if not more, effective than similar interventions
      applied in high income countries.

PMID- 18814198
TI  - Persistent apathy in Alzheimer's disease as an independent factor of rapid
      functional decline: the REAL longitudinal cohort study.
AB  - OBJECTIVE: To determine the role of persistent apathy in rapid loss of autonomy
      in Instrumental Activities of Daily Living (IADL) in women with Alzheimer s
      disease (AD), taking into account the grade of cognitive decline. METHODS: The
      study was conducted on 272 women from the French REAL cohort. At inclusion
      patients had a Mini-Mental State Examination (MMSE) score between 10-26. A rapid
      functional decline was defined as a yearly drop of 4 points or more on the 14
      point IADL Lawton scale. Persistent apathy was defined as a frequency score equal
      to 3 or 4 on the Neuro-Psychiatric Inventory at the three consecutive 6-monthly
      assessments. RESULTS: 27.6% of women had rapid functional decline in 1 year and
      22.1% of them had persistent apathy. A logistic regression analysis showed that,
      in addition to cognitive decline, persistent apathy plays a role in rapid
      functional decline in 1 year. For example, for a 3-point decline in MMSE in 1
      year, the probability of a rapid loss in IADL is 0.45 for women with persistent
      apathy compared with 0.28 for those without persistent apathy. CONCLUSIONS: In
      this study, a rapid loss in IADL score was partly explained by persistent apathy.

PMID- 18814199
TI  - Smell test predicts performance on delayed recall memory test in elderly with
      depression.
AB  - INTRODUCTION: Elderly with depression are at increased risk for cognitive
      dysfunction and dementia. Smell tests are correlated with performance on
      cognitive tests in the elderly and therefore might serve as a screening test for
      cognitive impairment in depressed elderly. PURPOSE: To assess the validity of the
      CC-SIT (Cross-Cultural Smell Identification Test) as a screening test for
      cognitive impairment in elderly with depression. METHODS: Forty-one patients,
      aged 60 and over, were assessed with the CC-SIT and CVLT (California Verbal
      Learning Test) after 3 months treatment of a Major Depressive Episode (DSM-IV) at
      the Day Hospital for Depression, Baycrest. Patients already diagnosed with
      dementia, or other psychiatric and neurological disorders, were excluded.
      Receiver Operating Characteristics (ROC) analysis was applied to assess the CC
      SIT's accuracy in identifying individuals with impairment (2 SD below the mean
      for age and education or less) on CVLT delayed recall trials. RESULTS: Forty-one
      patients (33 women and eight men) were assessed. Mean age was 76.8 (SD: 6.5),
      mean HRSD scores before treatment was 22.0 (SD: 5.1). Nine patients had
      impairment on CVLT delayed recall measures. The area under the ROC curve was
      0.776 (95% CI = 0.617-0.936). CONCLUSIONS: Our results support the use of the CC
      SIT as a screening tool for cognitive impairment among elderly with depression as
      an indicator for the need of a comprehensive neuropsychological evaluation.
      Replication with larger samples is necessary.

PMID- 18814200
TI  - A cross cultural review of the ethical issues in dementia care in Kerala, India
      and The Netherlands.
AB  - BACKGROUND: The paper explores the diverse ethical issues in the care of persons
      with dementia, in the Netherlands and Kerala, India. These cross-cultural data
      are used to suggest newer ways for addressing the ethical issues in a mutually
      enhancing manner. METHODS: A thorough review of the literature focusing on
      ethical aspects of the care for persons with dementia. RESULTS: The medical
      paradigm is dominant in the Netherlands and awareness of dementia as an organic
      brain disease is low in Kerala. Institutionalized care is more common in the
      Netherlands and home-based care is the norm in Kerala. Institutional care is
      costly, whereas home-based care is stressful for caregivers. The advanced
      directive plays an influential role in the Netherlands, but this mechanism is yet
      to evolve in Kerala. The legal and social setting of the Netherlands has a strong
      influence on physician decision-making concerning end of life issues. In Kerala,
      discussion of these matters is nearly unknown. CONCLUSION: Limited awareness of
      dementia in Kerala should be addressed in public forums, which can then be used
      to garner governmental support. The predominantly institutional model of care
      giving in the Netherlands and home-based care-giving in Kerala, each have their
      strengths; policy makers in both societies can usefully apply the values and
      merits inherent in both models. A culturally appropriate implementation of the
      advanced directive will have beneficial medical, social, and economic impacts in
      Kerala. The remarkable disparity between the Netherlands and Kerala in dealing
      with end-of-life issues will allow more philosophically and socially informed
      ways of addressing the ethical questions that arise in those situations.

PMID- 18814201
TI  - Cytotoxic xenicane diterpenes from the brown alga Padina pavonia (L.) Gaill.
AB  - Column chromatography of the hexane fraction of a methanol extract of Padina
      pavonia (L.) Gaill. collected from the Red Sea at Hurghada, Egypt yielded 18,19
      epoxyxenic-19-methoxy-18-hydroxy-4-acetoxy-6,9,13-triene (1) and 18,19-epoxyxenic
      18,19-dimethoxy-4-hydroxy-6,9,13-triene (2). The isolated compounds have various
      antitumor activities against lung carcinoma (H460) and liver carcinoma (HepG2)
      human cell lines (in vitro).

PMID- 18814202
TI  - Studies on the antioxidant and analgesic activities of Aztec marigold (Tagetes
      erecta) flowers.
AB  - Commercially available Aztec marigold (Tagetes erecta) flower extract (Af.Cr) was
      evaluated for the in vitro antioxidant activity and in vivo analgesic effect on
      acetic-acid-induced abdominal writhing. The results revealed the presence of
      pronounced antioxidant potential in Aztec marigold flowers and a dose-dependent
      (100 and 300 mg/kg) analgesic effect. The antioxidant and analgesic activities
      obtained seem to be in good accordance with the medicinal uses of Aztec marigold
      as an anti-inflammatory and analgesic.

PMID- 18814203
TI  - Kinetics of enzyme inhibition by active molluscicidal agents ferulic acid,
      umbelliferone, eugenol and limonene in the nervous tissue of snail Lymnaea
      acuminata.
AB  - Ferulic acid, umbelliferone (Ferula asafoetida), eugenol (Syzygium aromaticum)
      and limonene (Carum carvi) are active molluscicidal components that inhibited the
      activity of alkaline phosphatase and acetylcholinesterase in in vivo and in vitro
      exposure of Lymnaea acuminata. It was observed that ferulic acid, umbelliferone
      and eugenol are competitive and limonene is a competitive-non-competitive
      inhibitor of alkaline phosphatase. Ferulic acid and umbelliferone are
      competitive, whereas eugenol and limonene are competitive-non-competitive and
      uncompetitive inhibitors of acetylcholinesterase, respectively.

PMID- 18814204
TI  - Effect of traditional Chinese medicine Shu-mai-tang on angiogenesis,
      arteriogenesis and cardiac function in rats with myocardial ischemia.
AB  - Ischemic heart disease is one of the leading causes of morbidity and mortality
      worldwide. Shu-mai-tang (SMT) is a traditional Chinese medicine for the treatment
      of ischemic heart disease. To better understand the underlying cardioprotection
      mechanisms of SMT on myocardial ischemia (MI), the effect of SMT on angiogenesis,
      arteriogenesis and cardiac function was investigated in a rat model of MI, as
      well as the potential mechanism. Rats with a ligated left anterior descending
      coronary artery (MI model) were randomized (24 rats/group) to receive
      SMT/LY294002 [phosphatidylinositol 3-kinase (PI3K) inhibitor], SMT or no
      treatment. A sham-operation group was included. It was demonstrated that 2 and 4
      weeks after treatment the oral administration of SMT significantly increased
      capillaries and arterioles, suppressed myocardial fibrosis, as well as
      significantly increased cardiac phosphorylation of Akt, vascular endothelial
      growth factor (VEGF) and platelet-derived growth factor (PDGF-BB) levels and
      functional improvement. PI3K inhibitor down-regulated SMT-induced angiogenesis
      and arteriogenesis. These novel therapeutic properties of SMT to induce the
      reconstitution of stable blood supply networks, reverse LV remodeling may offer
      an alternative therapy for the treatment of ischemic heart disease. The potential
      mechanism may be that SMT promotes VEGF and PDGF-BB-mediated angiogenesis and
      arteriogenesis through the PI3K/Akt signaling pathway.

PMID- 18814205
TI  - Inhibitory effects of xanthohumol from hops (Humulus lupulus L.) on human
      hepatocellular carcinoma cell lines.
AB  - Xanthohumol is one of the main flavonoids in hop extracts and in beer. Very few
      investigations of xanthohumol have studied hepatocellular carcinoma. In this
      study, the inhibitory effects of xanthohumol on human hepatocellular carcinoma
      cell lines were investigated. The IC(50) values of xanthohumol for two
      hepatocellular carcinoma cell lines and one normal hepatocyte cell line were 108,
      166 and 211 microm, respectively. Normal murine hepatocyte cell line had more
      resistance to xanthohumol than hepatocellular carcinoma cell lines. Besides, the
      inhibitory effects of xanthohumol on human hepatocellular carcinoma cell lines
      were attributed to apoptosis as indicated in the results of flow cytometry,
      fluorescent nuclear staining and electrophoresis of oligonucleosomal DNA
      fragments. Hop xanthohumol was more efficient in the growth inhibition of
      hepatocellular carcinoma cell lines than the flavonoids silibinin and naringin
      from thistle and citrus. It was shown for the first time that xanthohumol from
      hops effectively inhibits proliferation of human hepatocellular carcinoma cells
      in vitro.

PMID- 18814206
TI  - Antioxidant and free-radical scavenging activities of Allium roseum and Allium
      subhirsutum.
AB  - This study was designed to examine the antioxidant and free-radical scavenging
      activities of two Allium species, Allium roseum and Allium subhirsutum. This
      study reports the results concerning bulb, stalk and leaf antioxidant enzyme
      activities (superoxide dismutase, catalase, guaiacol peroxidase and glutathione
      peroxidase), quantities of malonyldialdehyde, (*)OH and O(2) (*-) radicals and
      total antioxidant capacity determined by the FRAP method. Scavenging activities
      were determined by ESR method. The total antioxidant capacity was the highest in
      the leaves of Allium roseum. Among the investigated organs the leaves exhibited
      the highest antioxidant activities in all investigated Allium species. The
      highest ESR (84.61%) scavenger activity was observed in the leaves of Allium
      roseum.

PMID- 18814207
TI  - In vitro effects of beetroot juice and chips on oxidative metabolism and
      apoptosis in neutrophils from obese individuals.
AB  - Oxidative stress and inflammation are involved in the development of obesity.
      Beetroot (Beta vulgaris var. rubra) is a food ingredient containing betalain
      pigments that show antioxidant activity. The in vitro effect of beetroot juice
      and chips on oxidative metabolism and apoptosis in neutrophils from obese
      individuals has been investigated. Fifteen obese women (aged 45 +/- 9 years, BMI
      >30 kg/m2) and nine healthy controls (women, aged 29 +/- 11 years, BMI = 22.2 +/-
      1.6 kg/m2) were examined. The investigated products were used as concentrates and
      after transport and digestion in an artificial gastrointestinal tract. Neutrophil
      oxidant production, in response to phorbol 12-myristate 13-acetate, was
      characterized by luminol-dependent chemiluminescence and a flow cytometric
      dichlorofluorescin oxidation assay. Caspase-3 activity, a marker of apoptosis,
      was measured by cleavage of the fluorogenic substrate Ac-DEVD-AMC. Neutrophils
      from obese individuals had a significantly higher ROS production compared with
      the controls (p < 0.05). Beetroot products inhibited neutrophil oxidative
      metabolism in a concentration-dependent manner. Also observed were the pro
      apoptotic effects of beetroot at a concentration range of 0.1-10% in 24 h culture
      of stimulated neutrophils. These natural products (in both the liquid and solid
      state) have antioxidant and antiinflammatory capacity, and could be an important
      adjunct in the treatment of obesity.

PMID- 18814208
TI  - The effect of Anethum graveolens L. (dill) on corticosteroid induced diabetes
      mellitus: involvement of thyroid hormones.
AB  - An investigation was made to evaluate the role of Anethum graveolens L. (dill)
      leaf extract in the regulation of corticosteroid-induced type 2 diabetes mellitus
      in female rats. In dexamethasone-treated animals (1 mg/kg for 22 days) an
      increase in serum concentration of insulin and glucose and in hepatic lipid
      peroxidation (LPO) was observed. However, there was a decrease in serum
      concentration of thyroid hormones and in the endogenous antioxidant enzymes, such
      as superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH) in
      liver. In animals treated with an equivalent amount of dexamethasone for a
      similar period (22 days) when received the leaf extract (100 mg/kg b.wt/d.) for
      last 15 days a decrease in the concentration of both serum glucose and insulin
      was observed, indicating the potential of the plant extract in the regulation of
      corticosteroid-induced diabetes. Dexamethasone-induced alterations in the levels
      of thyroid hormones as well as in hepatic LPO, SOD, CAT and GSH were also
      reversed by the plant extract.

PMID- 18814209
TI  - Effects of hyperin, isoquercitrin and quercetin on lipopolysaccharide-induced
      nitrite production in rat peritoneal macrophages.
AB  - The extract of the root of Acanthopanax chiisanensis Nakai is used for the
      treatment of inflammation. To analyse the action mechanism of this extract, the
      effect of hyperin (quercetin-3-O-beta-d-galactose) isolated from the ethyl
      acetate fraction of the root of A. chiisanensis on nitrite production and
      induction of inducible nitric oxide synthase (iNOS) in lipopolysaccharide (LPS, 1
      microg/mL)-stimulated rat peritoneal macrophages were examined. The effect of the
      structurally related compounds, isoquercitrin (quercetin-3-O-beta-d-glucose) and
      quercetin (an aglycone of the two compounds) isolated from the extract of the
      leaves of Vaccinium koreanum Nakai was also examined to compare the effect. It
      was shown that hyperin inhibited the LPS-induced iNOS expression and nitrite
      production. Of the three compounds, quercetin showed the most potent inhibitory
      activity. The phosphorylation of p44/42 mitogen activated protein kinase (MAPK),
      p38 MAPK and c-Jun N-terminal kinase (JNK) were also inhibited by these
      compounds. These findings suggested that hyperin in the extract of the root of A.
      chiisanensis inhibits nitric oxide (NO) production through inhibition of the
      expression of iNOS by attenuation of p44/p42 MAPK, p38 MAPK and JNK, and thus
      participates in the antiinflammatory activity of the extract.

PMID- 18814210
TI  - Effect of Peganum harmala or its beta-carboline alkaloids on certain antibiotic
      resistant strains of bacteria and protozoa from poultry.
AB  - In the present study the antimicrobial potential of various extracts from 12
      medicinal plants has been investigated in vitro on multiple antibiotic resistant
      pathogens and some selected protozoa isolated from poultry. The initial
      examination was performed on E. coli (n = 10) using disc and agar well diffusion
      assays. Only two plants, Peganum harmala (seeds) and Eucalyptus globulus (leaves)
      showed positive responses. The active extracts were also investigated against an
      additional 19 bacteria and the clonal cultures of three protozoa (Histomonas
      meleagridis, Tetratrichomonas gallinarum and Blastocystis sp.). Only Peganum
      harmala was found to inhibit the growth of all bacteria and protozoa at 0.38-1.55
      mg/mL and 0.63-1.65 mg/mL, respectively. To investigate the potential role of
      alkaloids in crude extracts of Peganum harmala, four known beta-carbolin
      alkaloids were quantified and their antimicrobial activity was compared using a
      microdilution assay. Harmaline was found to be in the highest concentration
      followed by harmine and harmalol, whereas harmane could not be detected. The
      activity of the pure alkaloids was in the order harmane > harmaline > harmalol >
      or = harmine for all bacteria, while for protozoa, it was different depending on
      the microorganism. It is concluded that Peganum harmala or its alkaloids could
      probably be used for the control of antibiotic resistant isolates of bacteria as
      well as protozoa.

PMID- 18814211
TI  - Antibacterial activity of [10]-gingerol and [12]-gingerol isolated from ginger
      rhizome against periodontal bacteria.
AB  - Ginger (Zingiber officinale Roscoe) has been used widely as a food spice and an
      herbal medicine. In particular, its gingerol-related components have been
      reported to possess antimicrobial and antifungal properties, as well as several
      pharmaceutical properties. However, the effective ginger constituents that
      inhibit the growth of oral bacteria associated with periodontitis in the human
      oral cavity have not been elucidated. This study revealed that the ethanol and n
      hexane extracts of ginger exhibited antibacterial activities against three
      anaerobic Gram-negative bacteria, Porphyromonas gingivalis ATCC 53978,
      Porphyromonas endodontalis ATCC 35406 and Prevotella intermedia ATCC 25611,
      causing periodontal diseases. Thereafter, five ginger constituents were isolated
      by a preparative high-performance liquid chromatographic method from the active
      silica-gel column chromatography fractions, elucidated their structures by
      nuclear magnetic resonance spectroscopy and electrospray ionization mass
      spectrometry and their antibacterial activity evaluated. In conclusion, two
      highly alkylated gingerols, [10]-gingerol and [12]-gingerol effectively inhibited
      the growth of these oral pathogens at a minimum inhibitory concentration (MIC)
      range of 6-30 microg/mL. These ginger compounds also killed the oral pathogens at
      a minimum bactericidal concentration (MBC) range of 4-20 microg/mL, but not the
      other ginger compounds 5-acetoxy-[6]-gingerol, 3,5-diacetoxy-[6]-gingerdiol and
      galanolactone.

PMID- 18814212
TI  - The antiinflammatory, gastroprotective and antioxidant activities of Hieracium
      gymnocephalum extract.
AB  - The present study investigated the antiinflammatory, gastroprotective and
      antioxidant activities of a CH(2)Cl(2) extract of western Balkan endemic
      Hieracium gymnocephalum Griseb. ex Pant. (Compositae). The carrageenan-induced
      rat paw oedema test was used as an experimental model for screening the
      antiinflammatory activity. The extract was administrated p.o. in doses of 25, 50,
      100 and 200 mg/kg to rats and its effects compared with indomethacin, used p.o.
      as a reference drug. The results showed that the investigated extract reduced the
      oedema in a concentration-dependent manner. The obtained antiinflammatory effect
      was 5.9%, 11.7%, 31.2% and 44.1% at doses of 25, 50, 100 and 200 mg/kg,
      respectively, being statistically significant at a dose of 100 mg/kg.
      Indomethacin had a strong antiinflammatory effect of 73.4% at a dose of 8 mg/kg,
      but caused large gastric lesions. When the plant extract in the highest tested
      dose (200 mg/kg) was concomitantly given with indomethacin, the antiinflammatory
      effect was slightly enhanced, but the gastric lesions were significantly reduced.
      The antioxidant activity of the H. gymnocephalum extract, investigated using DPPH
      radical assay, OH-radical assay and TBA-test, was not substantial.

PMID- 18814213
TI  - Chemical composition and antiproliferative activity of essential oil from the
      leaves of a medicinal herb, Schefflera heptaphylla.
AB  - Schefflera heptaphylla (L.) Frodin is a medicinal herb widely used as a main
      ingredient of the popular health tea formulation against infections in Southern
      China. Twenty-seven volatile compounds were identified by GC-MS analysis from the
      essential oil obtained from the leaves of S. heptaphylla, and 17 of them belonged
      to monoterpenes or sesquiterpenes. The main volatile constituent in S.
      heptaphylla was found to be a monoterpene, beta-pinene, comprising about 22% of
      the total volatile components. The essential oil showed significant
      antiproliferative activity against three cancer cell lines, MCF-7, A375 and HepG2
      cells, with IC50 values of 7.3 microg/mL, 7.5 microg/mL and 6.9 microg/mL,
      respectively. The result of the cytotoxicity assay indicates that (-)-beta-pinene
      and (+)-beta-pinene (commercially available from Sigma) also possessed
      antiproliferative activity against the cancer cells MCF-7, A375 and HepG2 with
      IC50 values ranging from 147.1 to 264.7 microm.

PMID- 18814214
TI  - Inhibition of cytochrome P450 enzymes by rhein in rat liver microsomes.
AB  - Rhein, an active ingredient extensively found in plants such as Aloe, Cassitora
      L., rhubarb and so on, has been used for a long time in China. Pharmacological
      tests revealed that rhein not only had a strong antibacterial action, but also
      may be useful in cancer chemotherapy as a biochemical modulator. Its therapeutic
      action and toxicity is still the subject of considerable research. With microsome
      incubation assays in vitro and HPLC methods, the inhibition of rat liver CYP1A2,
      CYP2C9, CYP2D6, CYP2E1 and CYP3A enzymes by rhein were studied kinetically. The
      results showed the most inhibition of CYP2E1 by rhein (K(i) = 10 microm, mixed);
      CYP3A and CYP2C9 were also inhibited by rhein, K(i) = 30 microm (mixed) and K(i)
      = 38 microm (mixed), respectively; rhein revealed some inhibition of CYP1A2 (K(i)
      = 62 microm, uncompetitive) and CYP2D6 (K(i) = 74 microm, mixed). Drug-drug
      interactions, especially cytochrome P450 (CYP)-mediated interactions, cause an
      enhancement or attenuation in the efficacy of co-administered drugs. Inhibition
      of the five major CYP enzymes observed for rhein suggested that changes in
      pharmacokinetics of co-administered drugs were likely to occur. Therefore,
      caution should be paid to the possible drug interaction of medicinal plants
      containing rhein and CYP substrates.

PMID- 18814215
TI  - Techniques for chorionic villus sampling and amniocentesis: a survey of practice
      in specialist UK centres.
AB  - OBJECTIVES: Guidelines exist for amniocentesis and chorionic villous sampling
      (CVS) practice, but there is no consensus regarding individual techniques. Our
      survey sought to review current practice within specialist centres in the United
      Kingdom. METHODS: RCOG sub-specialist training centres were invited to complete a
      postal questionnaire, seeking their consultants' primary choices for
      amniocentesis and CVS techniques. Information sought included needle choice,
      local anaesthetic (LA), suction methods, quantity of samples obtained; and with
      regard to CVS, preferred approach [transcervical (TC) or transabdominal (TA)].
      RESULTS: Response rate was 96% providing information on 111 consultants (111
      amniocentesis/90 CVS). During amniocentesis, 86% use 22G needles and 70% are
      helped by an assistant who aspirates a set liquor volume (69%). For CVS, 98% use
      a TA approach, 89% use LA, and 29% an 18G single needle with 38% preferring a
      17/19G double needle but no clear consensus regarding the use of assistants.
      CONCLUSIONS: There is some agreement among specialists in the United Kingdom
      regarding techniques for invasive prenatal diagnosis. For amniocentesis, most
      operators use 22G needles, with an assistant to aspirate a set volume of fluid
      regardless of gestation. For CVS, there is considerable variation in needle
      choice, although most operators use a TA approach with LA.

PMID- 18814216
TI  - Method validation for measurement of hair nicotine level in nonsmokers.
AB  - The development of strategies to address the growing worldwide burden of exposure
      to secondhand smoke (SHS) would be facilitated by sensitive and accurate methods
      for assessing SHS exposure. Hair provides a readily available matrix for
      assessing biomarkers of typical SHS exposure. We developed and applied an
      optimized analytical method using an isotope dilution gas chromatography-mass
      spectrometry (GC/MS) for hair nicotine measurement. The utility of this optimized
      method is illustrated by presenting data on SHS exposure of women and children
      from 31 countries. Using this isotope dilution method with spiked samples (3.3
      ng/mg), we found that the greatest hair nicotine extraction efficiency was
      obtained with a 60 min shaking time. In the field study (n = 2400), a positive
      association was evident between hair nicotine concentrations from nonsmokers and
      higher numbers of cigarettes smoked per day in a household.

PMID- 18814217
TI  - Usage patterns and 2-year outcomes with the TAXUS express stent: results of the
      US ARRIVE 1 registry.
AB  - BACKGROUND: It is unclear how well the long-term safety and effectiveness of drug
      eluting stents observed in tightly defined randomized controlled trials (RCT)
      translates to expanded use in routine practice. METHODS: The FDA-mandated TAXUS
      Express(2) ARRIVE 1 postmarket registry was designed to consecutively enroll
      patients receiving > or = 1 TAXUS stent in low-, medium-, and high-volume US
      sites (n = 50). All cardiac events plus an additional 20% sample of records were
      monitored and all endpoints were independently adjudicated. RESULTS: Detailed
      follow-up data through 2 years were compiled for 2,487 patients (95%). Simple-use
      (on-label) ARRIVE 1 patients (35%) had outcomes similar to 4 pooled TAXUS RCTs
      for death (3.5% vs. 3.4%, respectively, P = 0.78), Q-wave myocardial infarction
      (QWMI, 0.7% vs. 0.9%, P = 0.72), and stent thrombosis (ST, 2.2% vs. 1.2%, P =
      0.12), but lower target vessel revascularization (7.8% vs. 13.4%, P < 0.0001).
      Compared with simple-use, cases representing expanded use to treat broader
      patient/lesion characteristics showed higher 2-year rates for death (7.4% vs.
      3.5%, respectively, P = 0.0003), target lesion revascularization (9.4% vs. 5.8%,
      P = 0.0031), and ST (3.4% vs. 2.2%, P = 0.061, concentrated early in the first
      year). CONCLUSIONS: By including methods usually found in RCT, ARRIVE 1 captured
      a broad spectrum of disease treated in standard practice with high levels of
      ascertainment of clinical outcomes. In the more complicated cases, expectedly
      higher adverse event rates were seen compared to that found in the simple-use
      cases or pivotal RCT. These results have now been included in the Directions for
      Use, to aid in physician and patient decision-making.

PMID- 18814218
TI  - Complete versus incomplete revascularization in patients with multivessel disease
      undergoing percutaneous coronary intervention with drug-eluting stents.
AB  - OBJECTIVES: To investigate the long-term prognostic implications of complete
      versus incomplete revascularization in multivessel coronary artery disease (MVD)
      patients undergoing percutaneous coronary intervention (PCI) with drug-eluting
      stent (DES). BACKGROUND: Coronary artery bypass grafting (CABG) in patients with
      MVD provides better outcomes when complete revascularization is achieved. There
      is a paucity of data on the outcomes of complete versus incomplete
      revascularization of MVD patients undergoing PCI, and currently there is no data
      available with DES. METHODS: Patients with MVD undergoing PCI with DES (sirolimus
      or paclitaxel-eluting stent) were included. Comparisons of long-term outcomes
      between completely versus incompletely revascularized patients were made. The
      primary outcome measure was the composite of cardiac death, nonfatal myocardial
      infarction (MI), or any revascularization. Secondary endpoints were the
      components of the composite endpoint. RESULTS: A total of 508 patients were
      considered for this analysis: 212 (41.7%) and 296 (58.3%) had complete and
      incomplete revascularization, respectively. The median follow-up was 27.0
      (interquartile range: 23.0-37.1) months. After adjusting for baseline
      characteristics, the hazard ratio (HR, 95% confidence interval) for complete
      revascularization was 0.43 (0.29-0.63, P < 0.0001) for the primary composite
      endpoint. Complete revascularization was associated with better outcomes for
      components of the composite endpoint: 0.37 (0.15-0.92, P = 0.03) for cardiac
      death, 0.34 (0.16-0.75 P = 0.008) for the composite of cardiac death or MI and
      0.45 (0.29-0.69, P = 0.0003) for any repeat revascularization. This association
      was confirmed in a propensity-matched population. CONCLUSIONS: Complete
      revascularization with DES of MVD patients is associated with lower rates of long
      term adverse events.

PMID- 18814219
TI  - High incidence of recurrent in stent thrombosis after successful treatment of a
      first in stent thrombosis.
AB  - OBJECTIVES: We attempted to investigate incidence and predictors of recurrent in
      stent thrombosis (IST) after successful treatment of a first IST. BACKGROUND: The
      occurrence of recurrent IST after successful treatment of a first IST may be a
      decisive factor for patient clinical outcome. However, incidence and predictors
      of recurrent IST are currently poorly described in the literature. METHODS:
      Between 2003 and 2005, 2,190 patients underwent a percutaneous coronary
      intervention in our center. During a median follow-up of 19.4 months, 49 patients
      (2.24%) presented a first definite IST. Patients presenting with a first IST were
      followed during an additional median period of 40 months. Their baseline
      characteristics were listed and cardiovascular events especially recurrent IST as
      defined by the Academic Research Consortium definition were systematically
      indexed. RESULTS: Altogether 39 (80%) patients were successfully treated with an
      effective reperfusion after percutaneous coronary intervention. Fourteen (36%)
      patients presented a recurrent IST and three presented multiple recurrent IST.
      The median occurrence time of recurrent IST was 5 days, range between 1 and 11
      days. Multivariate analysis identified history of neoplasia (HR = 11.53, 95% CI
      2.32-57.37, P = 0.003), residual diameter stenosis (HR = 1.15, 95% CI 1.02-1.29,
      P = 0.02), and residual dissection after treatment (HR = 8.78, 95% CI 1.85-41.62,
      P = 0.006), as independent predictors of recurrent IST. CONCLUSION: Recurrent IST
      is a frequent and early event after successful treatment of a first IST. Our
      results suggest that mechanical factors like residual dissection and residual
      diameter stenosis should be carefully tracked down. In addition, patients with
      multiple recurrent IST and the early time course of recurrent IST also suggest a
      potential role of inadequate antiplatelet therapy.

PMID- 18814220
TI  - Influence of surface modification on the in vitro corrosion rate of magnesium
      alloy AZ31.
AB  - In recent years, magnesium alloys have been proposed as a new class of metallic
      bioabsorbable implant material. Unfortunately, the production of hydrogen gas and
      an increase in alkalinity are both by-products of the degradation process of
      these materials. This necessitates the development of magnesium alloys with
      controlled degradation rates. Furthermore, biocompatible coatings that can delay
      the onset of corrosion would ensure that the mechanical integrity of the implant
      remains intact in the early stages of healing. This article explores the
      influence of surface modification by biomimetic calcium phosphate coating,
      biodegradable polymer coatings, and acid etching on the corrosion rate of the
      AZ31 magnesium alloy in simulated body fluid. Our results indicate that all of
      these surface treatments have a positive impact on the corrosion rate of the
      material and that in the early stages of implantation it is possible to tailor
      the corrosion rate through an appropriate choice of surface treatment.

PMID- 18814221
TI  - Hemodynamic evaluation of coronary artery bypass graft lesions using fractional
      flow reserve.
AB  - BACKGROUND: Coronary angiography is limited by its inability to assess the
      hemodynamic significance of a coronary artery stenosis. The assessment of the
      physiological significance of saphenous vein graft (SVG) lesions with a pressure
      wire to determine the fractional flow reserve (FFR) is lacking. METHODS: FFR was
      determined in 10 SVG lesions of 10 males who had stress myocardial perfusion
      imaging (MPI) prior to referral for percutaneous coronary intervention for
      clinical indications. RESULTS: All SVGs had a diameter stenosis (DS) > 50% and
      30% had a DS > or = 70%. A significant FFR was present in 30% of patients.
      Ischemia along the territory of the SVG was present in 20% of patients. The
      sensitivity, specificity, positive predictive value, negative predictive value,
      and accuracy of FFR < 0.75 for the detection of ischemia on stress MPI were 50,
      75, 33, 85, and 70%, respectively. The sensitivity, specificity, positive
      predictive value, negative predictive value, and accuracy of FFR < 0.75 for
      detecting > or = 70% DS on angiography were 33, 71, 33, 71, and 60%,
      respectively. There was no significant correlation between FFR and % DS (R(2) =
      0.1, P = 0.35). CONCLUSION: The use of FFR to assess the physiological
      significance of SVG lesions is feasible and provides an acceptable specificity
      and negative predictive value compared to stress MPI.

PMID- 18814222
TI  - In vitro cell infiltration and in vivo cell infiltration and vascularization in a
      fibrous, highly porous poly(D,L-lactide) scaffold fabricated by cryogenic
      electrospinning technique.
AB  - One of the obstacles limiting the application of electrospun scaffolds for tissue
      engineering is the nanoscale pores that inhibit cell infiltration. In this
      article, we describe a technique that uses ice crystals as templates to fabricate
      cryogenic electrospun scaffolds (CES) with large three-dimensional and
      interconnected pores using poly(D,L-lactide) (PLA). Manipulating the humidity of
      the electrospinning environment the pore sizes are controlled. We are able to
      achieve pore sizes ranging from 900 +/- 100 microm(2) to 5000 +/- 2000 microm(2)
      depending on the relative humidity used. Our results show that cells infiltrated
      the CES up to 50 microm in thickness in vitro under static culture conditions
      whereas cells did not infiltrate the conventional electrospun scaffolds. In vivo
      studies demonstrated improved cell infiltration and vascularization in the CES
      compared with conventionally prepared electrospun scaffolds. In gaining control
      of the pore characteristics, we can then design CES that are optimized for
      specific tissue engineering applications.

PMID- 18814223
TI  - Distal myocardial protection with intracoronary beta blocker when added to a Gp
      IIb/IIIa platelet receptor blocker during percutaneous coronary intervention
      improves clinical outcome.
AB  - OBJECTIVE: The present study tested the hypothesis that intracoronary (IC)
      propranolol improves clinical outcomes with percutaneous coronary intervention
      (PCI) when used with background Gp IIb/IIIa receptor blockade. BACKGROUND: We
      have previously shown that administration of a relatively large weight-based IC
      dose of the beta blocker propranolol before PCI decreases the incidence of post
      PCI myocardial infarction (MI) and improves short- and long-term outcome. It has
      previously been shown that administration of a Gp IIb/IIIa receptor blocker
      decreases post-PCI MI and improves short- and long-term clinical outcome.
      METHODS: Patients undergoing PCI (n = 400) were randomized in a prospective
      double-blind fashion to IC propranolol (n = 200) or placebo (n = 200) with
      eptifibatide administered to all the patients. Myocardial isoform of creatine
      kinase was measured during the first 24 hr and clinical outcomes at 30 days and 1
      year. RESULTS: MI after PCI was seen in 21.5% of placebo and 12.5% of propranolol
      patients (relative risk reduction 0.42; 95%CI 0.09, 0.63; P = 0.016). At 30 days,
      the composite end point of death, post-procedural MI, urgent target lesion
      revascularization, or MI after index hospitalization occurred in 22.5% of placebo
      vs. 13.5% of propranolol patients (risk reduction 0.43; 95%CI 0.08, 0.65; P =
      0.018). Similar results were observed at 1 year with adverse outcomes in 21.5% of
      propranolol and 32.5% of placebo patients (P = 0.01). CONCLUSION: IC propranolol
      administration with the background Gp IIb/IIIa receptor blockade significantly
      reduces the incidence of post-PCI MI and improves the short- and long-term
      clinical outcome when compared with a Gp IIb/IIIa blocker alone.

PMID- 18814224
TI  - The off- versus on-label use of medical devices in interventional cardiovascular
      medicine: clarifying the ambiguity between regulatory labeling and clinical
      decision-making, Part 1: PCI.
AB  - The Food and Drug Administration convened a special public meeting of the
      Circulatory System Devices Advisory Panel in late 2006 in response to data
      suggesting a small but potentially significant increased risk of stent thrombosis
      with drug-eluting stents (DES). This panel concluded that "off-label" DES use was
      associated with an increased risk of adverse outcomes compared with "on-label"
      use. In this commentary, we will discuss the role of product labeling in clinical
      decision-making during percutaneous coronary intervention, elucidate the issues
      that may arise from the conflation of the responsibilities of regulatory bodies
      and physicians, and offer a potential framework for their resolution.

PMID- 18814225
TI  - Techniques to enhance guide catheter support.

PMID- 18814226
TI  - Left ventricular unloading with intra-aortic counter pulsation prior to
      reperfusion reduces myocardial release of endothelin-1 and decreases infarction
      size in a porcine ischemia-reperfusion model.
AB  - OBJECTIVES: We tested the hypothesis that unloading the left ventricle with intra
      aortic balloon counter-pulsation just prior to reperfusion provides infarct
      salvage compared with left ventricular (LV) unloading postreperfusion or
      reperfusion alone. BACKGROUND: Previous reports demonstrated infarct salvage with
      complete LV unloading with an LVAD prior to reperfusion; however, partial LV
      unloading using intra-aortic balloon pumps (IABPs) has not been evaluated.
      METHODS: Twenty-eight Yorkshire pigs were subjected to 1 hr of left anterior
      descending artery occlusion and 4 hr of reperfusion. An IABP was inserted and
      activated just prior to reperfusion (IABP-Pre), or 15 min after reperfusion (IABP
      Post), or not at all (control). RESULTS: At baseline, the hemodynamic data were
      similar in the three groups. Myocardial infarct size expressed a percentage of
      zone at risk in control animals was 44.9% +/- 4.8%, IAPB-Pre group 20.9% +/- 5.1%
      (P < 0.05 compared to control), and IABP-Post group 33.2 +/- 6.1% (P = 0.16 vs.
      control group). There was a correlation between transcardiac endothelin-1 release
      at 15 min postreperfusion and infarct size (r = 0.59). CONCLUSION: LV unloading
      with an IABP prior to reperfusion reduces the extent of myocardial necrosis in
      hearts subjected to 1 hr of left anterior descending artery occlusion and 4 hr of
      reperfusion compared with either reperfusion alone or LV unloading after
      reperfusion. Inhibition of myocardial ET-1 release by LV unloading may be a
      significant mechanism of myocardial protection. These data suggest that in high
      risk STEMI patients, IABP unloading prior to reperfusion might be more beneficial
      than IABP placement postreperfusion.

PMID- 18814227
TI  - Femoral artery occlusion after using a suture-mediated arterial puncture closure
      device.
AB  - A femoral artery occlusion is a very rare complication after using a suture
      mediated arterial puncture closing device (APCD). The mechanism of the femoral
      artery occlusion is unclear and its standard management has not been established.
      This case describes a mechanism of femoral artery occlusion by a suture-mediated
      APCD and suggests a method of prevention and treatment.

PMID- 18814228
TI  - Usefulness of multidetector CT imaging to assess vascular stents in children with
      congenital heart disease: an in vivo and in vitro study.
AB  - OBJECTIVE: To evaluate varying CT settings to visualize pediatric vascular stents
      in comparison to digital angiography (DA). BACKGROUND: There is a great clinical
      interest in substituting noninvasive methods to follow up children with
      congenital heart disease after interventional treatment. MATERIALS AND METHODS:
      CT studies in small children with transcatheter placed stents were reviewed,
      retrospectively. Furthermore, eight stents were implanted in tubes and partially
      obstructed. CT exams were performed on varying scanners (4 up to 64 slices) with
      corresponding tube settings. The effects of dose on image quality were evaluated
      regarding stent size, strut thickness, and in-stent stenoses in comparison to DA.
      RESULTS: Fourteen children with 28 implanted stents were identified. Significant
      differences between higher and lower radiation settings were not found,
      corresponding with the phantom, where moderate tube setting showed the best
      results. In vitro, there was an improvement with increasing number of detector
      rows, which resulted in a decrease of stent strut overestimation (295% down to
      201%; P < 0.0001) and a better agreement with DA measurements for mild (78% up to
      91%; P = 0.003) and moderate in-stent stenoses (80% up to 99%; P = 0.0001).
      CONCLUSION: Higher radiation exposure settings did not improve image quality,
      suggesting that the exams could be performed at a lower radiation dose.

PMID- 18814229
TI  - Feasibility and efficacy of stent redilatation in aortic coarctation.
AB  - OBJECTIVES: We evaluated the efficacy and safety of stent redilation in patients
      with aortic coarctation (COA). METHODS AND RESULTS: In our retrospective study of
      28 stent redilation procedures on 22 patients, the interval between implantation
      and redilation ranged from 2.5 month to 11 years (median 18 months). Ten patients
      had native COAs, one had repaired interrupted aortic arch. The remaining patients
      had residual COAs after surgery. Stent redilation was successful in 26
      procedures. Pressure gradients decreased from a mean of 26 +/- 13.8 mm Hg to 7.9
      +/- 6.52 mm Hg (P < 0.001). The mean diameter of the stents increased from 9.19
      +/- 3.29 mm to 12.1 +/- 3.68 mm (P < 0.001). In a patient with Williams-Beuren
      syndrome, massive neointimal proliferation made stent redilation impossible. One
      other patient developed aortic aneurysm after redilation and was operated after 3
      years. CONCLUSIONS: Stent redilation for aortic COA is a safe and successful
      procedure.

PMID- 18814230
TI  - ROCKs are expressed in brain tumors and are required for glioma-cell migration on
      myelinated axons.
AB  - The interactions between migrating glioma cells and myelinated fiber tracts are
      poorly understood. We identified that C6 glioma cells can migrate along
      myelinated chicken retinal axons in a novel coculture, thereby expressing small
      GTPases of the Rho family and serine/threonine Rho-associated kinases (ROCKs). We
      found that the ROCK1 isoform is also highly expressed in native human high-grade
      gliomas. Glioma cells migrated faster in vitro along myelinated axons than on
      laminin-1, with the former but not the latter being specifically and reversibly
      blocked by the ROCK inhibitor Y27632. These data suggest that the mechanisms
      underlying the migration of glioma cells on myelinated axons differ from those
      underlying the migration on extracellular matrix molecules such as laminin-1.

PMID- 18814231
TI  - Upregulation of p21Cip1 in activated glial cells.
AB  - The cdk inhibitor p21(Cip1), also named p21(Cip1/Waf1), is intimately involved in
      coupling growth arrest to cellular differentiation in several cell types.
      p21(Cip1) is a multifunctional protein that might regulate cell-cycle progression
      at different levels. In a recent study, we found no differences in the rate of
      proliferation between glial cells from wild-type and p21(Cip1-/-) mice. In the
      present study, we examined differences in glial activation between glial cells
      from wild-type and p21(Cip1-/-) mice, using mixed glial cultures, microglia
      enriched cultures, and astrocyte-enriched cultures. We compared the effect of
      lipopolysaccharide and two forms (oligomeric and fibrillar) of the 1-42 beta
      amyloid peptide on glial activation. We observed an attenuation of nuclear
      translocation of the nuclear factor kappa-B in p21(Cip1-/-) glial cells, when
      compared with glial cells from wild-type mice. In contrast, tumor necrosis factor
      alpha release was enhanced in p21(Cip1-/-)microglial cells. In addition glial
      activation induced by lipopolysaccharide and the fibrillar form of the 1-42 beta
      amyloid peptide upregulated p21(Cip1). Our results support a role for p21(Cip1)
      in the activation of glial cells, particularly in microglia.

PMID- 18814232
TI  - Enteric viruses in pediatric diarrhea in Saudi Arabia.
AB  - Between September 1st, 2002 and August 31st, 2003, a panel of 1,000 stool samples
      was collected from patients presenting with diarrhea in the three major urban
      centers of Saudi Arabia; Riyadh, Mecca, and Jeddah. Each sample was tested for
      rotavirus, and astrovirus by ELISA, G and P type was determined for all
      rotaviruses. Adenoviruses were sought by hexon-specific PCR and identified by
      RFLP. A subset of 253 samples was also tested for norovirus by ELISA. Data were
      analyzed for seasonality of infection, patient nationality and likelihood of
      hospitalization. Although the overall incidence of rotavirus identification in
      acute diarrheal stool continued to decline, this was still the virus identified
      most commonly (6%). Norovirus accounted for 3.5%, astrovirus, 1.9% and
      adenovirus, 1.4%. Type G9 rotavirus was found to be present (and already common)
      in 2003, predating its first reported identification in the country in 2004. Most
      of the virus infections (and most of the G9 detections) occurred in April, the
      month following the occurrence of the Hajj in the study year. Although most
      viruses were spread equally in the population, rotaviruses were significantly
      more common in non-Saudis than in Saudi citizens. Overall the data are consistent
      with an increase in all virus infections following al Hajj and the potential
      introduction of novel strains (such as the G9 rotaviruses) by pilgrims.
      Hospitalization was significantly associated only with norovirus infections.

PMID- 18814233
TI  - Frequency and genotype of GB virus C among Iranian patients infected with HIV.
AB  - GB virus C (GBV-C) infection is frequent in patients infected with the human
      immunodeficiency virus (HIV) due to similar transmission routes of these viruses.
      The aim of this study was to determine the rate of infection and genotypic
      characteristics of GBV-C in this population. The presence of GBV-C RNA was
      determined in serum samples of 106 patients infected with HIV by reverse
      transcriptase-nested polymerase chain reaction. GBV-C genotypes were determined
      by direct sequencing. Hepatitis B surface antigen (HBsAg), hepatitis B surface
      antibody (anti-HBs), hepatitis C antibody (anti-HCV), alanine aminotransferase
      (ALT) levels, HIV viral load and CD4(+) count were also tested in all patients.
      The overall prevalence of GBV-C infection was 11.3% in HIV patients. There was no
      significant difference between patients with and without GBV-C infection
      regarding age, sex, route of transmission, viral load, ALT levels, HBV and HCV co
      infection and treatment with antiretroviral drugs. 66.7% of patients with GBV-C
      had a CD4(+) count > or = 200 and 33.3% had a CD4(+) count < 200 cells/mm(3).
      Phylogenetic analysis revealed that all GBV-C isolates were genotype 2, and
      classified as subtype 2a. GBV-C infection is relatively common in patients
      infected with HIV. The prevailing GBV-C genotype 2a in this study group concurred
      with reports from other parts of the Middle East.

PMID- 18814234
TI  - Congenital aortic stenosis: a novel technique for ventricular pacing during
      valvuloplasty.
AB  - OBJECTIVES: The main objective of this study is to describe a new technique for
      rapid ventricular pacing to maintain balloon stability during balloon aortic
      valvuloplasty (BAV) without using transvenous temporary pacemaker electrode.
      BACKGROUND: The safety and efficacy of rapid right ventricular pacing to
      facilitate balloon stability during BAV has been previously reported. However, it
      necessitates an additional femoral venous access, an additional sheath, and a
      temporary pacemaker electrode. METHODS: This was a prospective pilot study. Rapid
      ventricular pacing was performed through back-up guidewires inserted into the
      left ventricle for balloon advancement and by an adhesive patch placed on the
      back of the patient. The technique was performed during BAV procedure in all of
      15 consecutive children diagnosed as congenital aortic stenosis. Pacing was
      performed at a rate decreasing systolic aortic pressure to the point of 40-50% of
      baseline. RESULTS: The technique was successful in all patients. Effective
      capture, stable pacing, and balloon stability were achieved in all children using
      very low outputs. No sustained arrhythmias or other procedure-related
      complications occurred. Mean aortic valve gradient decreased from 68.5 +/- 20.4
      mm Hg to 20.4 +/- 10.2 mm Hg. Degree of aortic regurgitation progressed from
      grade 0 to 1 in three patients and remained unchanged in 12 patients.
      CONCLUSIONS: This study demonstrated that back-up guidewires can be used
      effectively and safely for pacing during BAV procedures. This technique omits
      probable complications related to a second vascular access and may shorten the
      procedure time and decreases costs by eliminating the use of an additional sheath
      and a temporary pacemaker electrode.

PMID- 18814235
TI  - Promoting neurite outgrowth from spiral ganglion neuron explants using
      polypyrrole/BDNF-coated electrodes.
AB  - Release of neurotrophin-3 (NT3) and brain-derived neurotrophic factor (BDNF) from
      hair cells in the cochlea is essential for the survival of spiral ganglion
      neurons (SGNs). Loss of hair cells associated with a sensorineural hearing loss
      therefore results in degeneration of SGNs, potentially reducing the performance
      of a cochlear implant. Exogenous replacement of either or both neurotrophins
      protects SGNs from degeneration after deafness. We previously incorporated NT3
      into the conducting polymer polypyrrole (Ppy) synthesized with para-toluene
      sulfonate (pTS) to investigate whether Ppy/pTS/NT3-coated cochlear implant
      electrodes could provide both neurotrophic support and electrical stimulation for
      SGNs. Enhanced and controlled release of NT3 was achieved when Ppy/pTS/NT3-coated
      electrodes were subjected to electrical stimulation. Here we describe the release
      dynamics and biological properties of Ppy/pTS with incorporated BDNF. Release
      studies demonstrated slow passive diffusion of BDNF from Ppy/pTS/BDNF, with
      electrical stimulation significantly enhancing BDNF release over 7 days. A 3-day
      SGN explant assay found that neurite outgrowth from explants was 12.3-fold
      greater when polymers contained BDNF (p < 0.001), although electrical stimulation
      did not increase neurite outgrowth further. The versatility of Ppy to store and
      release neurotrophins, conduct electrical charge, and act as a substrate for
      nerve-electrode interactions is discussed for specialized applications such as
      cochlear implants.

PMID- 18814236
TI  - Single pediatric center experience with multiple device implantation for complex
      secundum atrial septal defects.
AB  - OBJECTIVES: We analyzed the efficacy and complications of placing multiple
      transcatheter devices to correct complex ASD in a primarily pediatric population.
      BACKGROUND: Limited pediatric information exists regarding the safety and
      efficacy of using multiple devices for secundum atrial septal defects (ASD) when
      multiple defects are present. METHODS: Cath lab, echo, and clinical data were
      reviewed for 238 patients who underwent device closure of secundum ASD from 2000
      to 2007 at a single pediatric center. Of those requiring multiple devices (n =
      15), residual shunting and complications were assessed. RESULTS: 238 patients
      (mean age 12 yrs; 80% < 16 yrs) underwent transcatheter ASD closure. 34 (14%) had
      multiple ASD, but only 15 received multiple devices (2 devices in 14 and 3
      devices in 1). The mean age and weight (12 yrs; 35 kg) represent a younger
      population than previously reported. Only 3 were > 15 yrs, with a median age of
      10.8 yrs (range 2-31). There was no compromise or obstruction to surrounding
      structures, and no device embolization or erosion was noted. A tiny thrombus was
      observed on the right sided screw of one device with no clinical sequelae. One
      patient (age 31 yrs) died at home 30 days post procedure from cardiac tamponade.
      Autopsy revealed the 3 intact devices in stable position without evidence of
      erosion. Latest available echo follow-up for the group revealed functional
      resolution of atrial level shunting in all patients. CONCLUSION: Multiple devices
      can safely and effectively be implanted in the pediatric population to close
      complex ASD.

PMID- 18814237
TI  - Transnasal transesophageal echocardiography: a new approach for the PFO occlusion
      in awake patients.
AB  - OBJECTIVES: To reduce risks, discomfort, cost, and operative time for
      percutaneous patent foramen ovale (PFO) closure, we propose to perform this
      procedure under transesophageal echo-guidance using a 10 Fr. catheter introduced
      through nasal way (TEENW). BACKGROUND: Transesophageal or intracardiac
      echocardiography is commonly used to guide percutaneous PFO closure. Sedation
      needed quite frequently during transesophageal echocardiography, increased
      patients' discomfort, procedure prolongation, costs, use of both femoral veins,
      and additional intracardiac manipulations are the main limitations of standard
      techniques. METHODS: We enrolled 20 consecutive patients with a history of
      cerebral ischemia and PFO with right-to-left shunt. In 15 patients Amplatzer PFO
      occluder was used, whereas in five patients with longer PFO tunnel (>10 mm)
      Cardia Intrasept was selected. Without sedation, a multifrequency monoplane
      probe, developed for intracardiac echocardiography, was introduced into the
      nostril and advanced forward the esophagus. Then under echo guidance, the closing
      device was presented, opened and released. RESULTS: Procedure lasted for an
      average of 33.3 min, and no complications were seen. At procedure's completion,
      six patients showed persistence of reduced shunt during Valsalva manoeuvre. At
      six-month follow-up, shunts disappeared in all patients. CONCLUSION: TEENW is
      safe and well tolerated, and images' quality is high enough to deserve widespread
      adoption of this technique for PFO closure.

PMID- 18814238
TI  - mRNAs of tyrosine hydroxylase and dopa decarboxylase but not of GD2 synthase are
      specific for neuroblastoma minimal disease and predicts outcome for children with
      high-risk disease when measured at diagnosis.
AB  - Several transcripts have been claimed to be clinically valuable for detecting
      minimal disease in neuroblastoma, but they have not been prospectively compared
      in a standardized manner. Tyrosine hydroxylase (TH), dopa decarboxylase (DDC) and
      GD2 synthase (GD2S) mRNAs were analyzed in 554 blood (PB) and bone marrow (BM)
      samples from 58 children with neuroblastoma. Samples from 44 children with other
      diseases served as controls. High transcript concentrations of TH, GD2S or DDC in
      PB or BM at diagnosis were associated with poor prognosis. TH in BM above median
      indicated worse outcome for a homogenous cohort with high-risk neuroblastoma
      (survival probability 91% for TH below median versus 33% for TH above median, p =
      0.009). The number of children with localized neuroblastoma with increased
      results in PB did not differ between the three transcripts. In these children,
      all without morphologically detectable neuroblastoma in BM, the number of
      patients with elevated GD2S in BM at diagnosis was significantly higher than for
      the other transcripts (10/16 elevated, p = 0.012). GD2S was elevated in PB from
      10/28 controls without neuroblastoma compared to 1/28 for TH and DDC (p < 0.001).
      In BM from these children GD2S was significantly elevated. We conclude that high
      expression of TH and DDC both in PB and BM corresponds to metastatic
      neuroblastoma at diagnosis, residual disease, and poor outcome. Children with
      high-risk neuroblastoma and low levels of TH in BM at diagnosis may be cured by
      current therapy. GD2S is less specific than TH and DDC mRNA for neuroblastoma
      detection in PB and BM.

PMID- 18814239
TI  - Risk factors for breast cancer in a black population--the Barbados National
      Cancer Study.
AB  - The Barbados National Cancer Study (BNCS) is a nationwide case-control study
      investigating environmental and genetic factors for breast cancer (BC) in a
      predominantly African-origin population with similar ancestry as African
      Americans. This report evaluates associations of incident BC in the BNCS to
      various factors, including demographic, anthropometric, reproductive and family
      history variables, not investigated previously in this population. The BNCS
      included 241 incident BC cases and 481 age-matched female controls, with mean
      ages of 57 and 56 years, respectively. In addition to a reported family history
      of BC in a close relative [odds ratios (OR) = 3.74, 95% CI (1.41, 9.90) in a
      parent; OR = 3.26 (1.47, 7.21) in a sibling], other factors associated with BC
      were older age at first full-term pregnancy [OR = 1.04 (1.00, 1.07)] and having a
      history of benign breast disease [OR = 1.88 (1.19, 2.99)]. Increased parity
      reduced the risk of BC [OR = 0.34 (0.15, 0.77) among those with >or=3 children].
      The reproductive patterns of African-Barbadian (AB) women tended to differ from
      those of African-American (AA) women (later age of menarche, earlier age at first
      pregnancy, higher frequency of lactation and infrequent use of exogenous
      hormones) and could help to explain their considerably lower postmenopausal
      incidence of BC. The relationship between reported family history and BC,
      combined with the associations noted for several reproductive and other
      variables, supports the genetic and environmental contributions to BC, which may
      vary in populations across the African diaspora. Further investigations of other
      populations may clarify these issues.

PMID- 18814240
TI  - Early aberrant insulin-like growth factor signaling in the progression to
      endometrial carcinoma is augmented by tamoxifen.
AB  - Tamoxifen is an important selective estrogen receptor (ER) modulator for
      treatment of steroid hormone positive breast cancer. In addition to the
      beneficial effect, tamoxifen is one risk factor for endometrial carcinoma (EnCa)
      development. We hypothesized that, (1) dysregulation of gene expression and
      protein phosphorylation of the insulin-like growth factor (IGF) and steroid
      hormone receptor-signaling occur early in benign endometrial tissues and (2)
      signaling differences would be detected between patients with or without
      tamoxifen treatment. Seventy-eight tissues, including 2 benign cohorts from
      patients treated with (n = 24) or without tamoxifen (n = 28) (hyperproliferative
      endometrium, hyperplasia, polyps), EnCa (n = 12) with endometrium controls (n =
      14) were analyzed for expression of 15 genes from the IGF and steroid hormone
      receptor-signaling, including the target genes Syncytin-1, PAX2 and c-myc. Total
      and phosphorylated protein expression were examined for ERalpha, PTEN, AKT, mTOR
      and Syncytin-1. Compared to controls similar significant deregulation of IGF and
      steroid hormone receptor-signaling, Syncytin-1 and PAX2 occurred in both benign
      cohorts, irrelevant of tamoxifen treatment. Comparing both benign cohorts with
      and without tamoxifen significant expression differences were noted. Increased
      total protein and phosphorylation of pERalpha-Ser118, pPTEN-Thr380, pAKT-Thr308,
      pAKT-Ser473, pmTOR-Ser2448 and Syncytin-1 were noted in early benign tissue
      stages associating with tamoxifen, especially polyps. Functional kinetic studies
      following tamoxifen treatment of the PTEN mutated RL95-2 EnCa cell line,
      demonstrated a doubling of phosphorylation of pERalpha-Ser118 and a 4.2-fold
      induction of pAKT-Thr308 along with Syncytin-1 induction. This study supports
      that dysregulated IGF and steroid hormone receptor signaling is prominent in
      endometrial benign stages and these alterations could represent clinical
      indicators for the risk of EnCa and also help in development of new therapies.

PMID- 18814241
TI  - Change of hepatitis B virus genotypes in acute and chronic infections in Japan.
AB  - During 35 years from 1971 to 2005, 153 patients with acute and 4,277 with chronic
      HBV infection visited the Toranomon Hospital in Tokyo, Japan. They were grouped
      into seven 5-year periods, and HBV genotypes/subgenotypes were determined.
      Patients with acute HBV infection were younger (P = 0.046), predominantly male (P
      = 0.004), possessed higher alanine aminotransferase levels (P < 0.001), positive
      more frequently for HBeAg (P < 0.001), and had lower HBV DNA loads (P = 0.014)
      than those with chronic infection. Sexual transmission was more frequent in
      patients with acute than chronic HBV infection (67% vs. 3%, P < 0.001). The
      number of patients with acute infection increased throughout 1971-2005. Patients
      with chronic infection increased since 1971, peaked in 1986-1990 and then
      decreased. The number of patients increased since 1990-2000 again, however,
      reflecting recent boost of acute HBV infection. The distribution of HBV genotypes
      was considerably different between patients with acute and chronic infections (A,
      B, and C: 28.6%, 10.3%, and 59.5% vs. 3.0%, 12.3%, and 84.5%, respectively, P <
      0.001). Since 1991, genotype A foreign to Japan started to increase sharply in
      patients with acute infection, and gradually in those with chronic infection.
      There was a trend for the foreign subgenotype B2/Ba to increase recently (P <
      0.05). Despite immunoprophylaxis of high-risk babies born to carrier mothers with
      hepatitis B e antigen, implemented nationally since 1986, acute and chronic
      infections with HBV have been increasing in Japan. Based on
      genotypes/subgenotypes changing with time, the resurgence of hepatitis B could be
      attributed to infections, with foreign HBV genotypes/subgenotypes, spreading
      swiftly by sexual contact.

PMID- 18814242
TI  - Clinical significance of a set of single nucleotide polymorphisms of hepatitis B
      virus core gene in Chinese Han patients with chronic hepatitis B.
AB  - To evaluate clinical significance of a set of SNPs of HBV core gene, a modified
      PCR-RFLP assay developed by Hannoun was adapted to determine HBV SNPs in 312
      Chinese Han patients with chronic hepatitis B. Five typical RFLP patterns were
      found and named RFLP patterns C, D, E, G, and C/G mixture. The distribution of
      RFLP patterns was as follows: C, 61.5%; D, 2.6%; E, 9.6%; G, 16.7%; C/G mixture,
      9.6%. The PCR amplicons of core gene were cloned into pGM-T, then colony PCR
      combined with RFLP and sequencing were used to confirm the presence of cleavage
      sites of Tsp509I and SNPs. 5 SNPs, A261T, A336C, A336T T337C and T385C, were
      found to be associated with RFLP patterns change and only SNP A336C or A336T
      caused the substitution of Glu-83 with Asp in HBcAg. The serum HBV DNA level in
      RFLP pattern C was higher than that in RFLP pattern G and C/G mixture,
      respectively, most possibly which associating with aminoacid change, Glu83Asp.
      The rate of elevated serum ALT levels in RFLP pattern C/G mixture was
      significantly lower than that in RFLP patterns C and G, respectively. The PCR
      amplicons of HBV S gene were sequenced and genotyped with HBV genotyping tools.
      It was found that RFLP patterns E and G were categorized into genotype B, RFLP
      pattern C showed two genotypes (B, C), and RFLP pattern D coincided with HBV
      genotype D, therefore, the modified PCR-RFLP can be adapted to determine HBV
      SNPs, not genotypes in Chinese Han patients with chronic hepatitis B.

PMID- 18814243
TI  - Intrafamilial transmission of hepatitis C virus: infection of the father predicts
      the risk of perinatal transmission.
AB  - The aims of the present study were to evaluate in a cohort of mothers infected
      with hepatitis C virus (HCV) the prevalence of HCV infection of their sexual
      partners, the influence of infection of the partners on perinatal transmission,
      and whether this influence is mediated by other well known risk factors for
      perinatal transmission. Forty-nine consecutive mothers infected with HCV who
      transmitted infection to their offspring and, as a control group, 557 consecutive
      mothers infected with HCV who did not transmit infection, together with their
      children and the fathers of the children who were also the sexual partners of the
      mothers were evaluated. History of intravenous drug use was significantly more
      frequent in women with partners infected with HCV than in women with partners not
      infected [115/180 (63.9%) vs. 87/401 (21.7%); relative risk (RR): 6.38, 95%
      confidence intervals (CI): 4.34-9.39, P < 10(-3)]. HCV infection was more
      frequent in the partners of mothers who transmitted perinatally HCV [23/49
      (46.9%) vs. 174/557 (31.2%); RR: 1.95, 95%CI: 1.08-3.51, P = 0.03]. Multivariate
      analysis demonstrated that paternal HCV infection is not a risk factor per se for
      perinatal HCV transmission, but its role is dependent on maternal intravenous
      drug use [adjusted RR: 1.23 (95%CI: 0.44-3.39, P = 0.6)]. In conclusion, the
      present study shows that partners of mothers infected with HCV with a history of
      intravenous drug use were at a higher risk of HCV infection. HCV infection of the
      father seems to be associated with perinatal transmission but this relationship
      is dependent on maternal history of intravenous drug use.

PMID- 18814244
TI  - Epstein-Barr virus encephalitis mimicking clinical and electroencephalographic
      characteristics of herpes simplex encephalitis.
AB  - A rare case of EBV encephalitis initially diagnosed as Herpes simplex infection
      is presented to highlight the importance of EBV specific intrathecal ELISA and
      liquor PCR based differential diagnosis when Herpes simplex encephalitis specific
      clinical symptoms, neuroimaging signs and electroencephalographic features are
      present. The case report also suggests that acyclovir treatment might be
      beneficial for the long term outcome in adult EBV encephalitis patients.

PMID- 18814245
TI  - GBV-C coinfection is negatively correlated to Fas expression and Fas-mediated
      apoptosis in HIV-1 infected patients.
AB  - Persistent coinfection with the apathogenic GB virus C (GBV-C) is associated with
      slower disease progression of human immunodeficiency virus (HIV)-1 infection. Aim
      of this study was to investigate whether Fas plays a role in this beneficial
      effect. Fas expression and susceptibility to Fas-mediated apoptosis (FMA) was
      analyzed in peripheral blood mononuclear cells (PBMCs) of HIV-1 patients
      coinfected and non-coinfected with GBV-C. Fas expression and function was
      evaluated in 42 GBV-C coinfected and 101 non-coinfected HIV-1 patients. Thirteen
      healthy and 11 Hepatitis C virus (HCV)-monoinfected individuals were analyzed as
      controls. Cell surface Fas expression was determined by flow cytometric analysis.
      Apoptosis was evaluated by staining with Annexin V and Viaprobe followed by
      multiparameter flow cytometry analysis. In untreated HIV-1 patients GBV-C
      coinfection was associated with significantly lower percentage of Fas expressing
      cells as compared to GBV-C non-coinfected individuals. Expression of Fas was
      directly correlated with sensitivity to Fas-mediated apoptosis. Sensitivity to
      FMA was unchanged in GBV-C coinfected patients. PBMCs of patients receiving
      highly active antiretroviral therapy (HAART) did not show such a difference.
      Untreated HIV-1 patients with GBV-C coinfection have reduced cell surface Fas
      expression. Lower FMA of T-cells might contribute to prolonged survival of GBV-C
      coinfected HIV-1 patients.

PMID- 18814246
TI  - Molecular characterization of influenza viruses circulating in Northern Italy
      during two seasons (2005/2006 and 2006/2007) of low influenza activity.
AB  - The influenza activity and circulation of influenza viruses in Lombardy (the most
      populous Italian region) were observed during two consecutive seasons (2005/2006
      and 2006/2007) characterized by low influenza activity by the Italian Influenza
      Surveillance Network. The molecular characteristics of circulating viruses were
      analyzed to evaluate the introduction of new variants and emergence of vaccine
      escape viruses. In both seasons, the epidemic in Lombardy was sustained almost
      exclusively by influenza A viruses, accounting for 80.5% and 93.6% of total
      detections, respectively, and the co-circulation of A/H3 viruses belonging to
      distinct phylogenetic groups was observed. The A/H1N1 viruses isolated during the
      2005/2006 season were closely related to A/New Caledonia/20/99, while the
      hemagglutinin (HA) sequences of the A/H1N1 viruses from the 2006/2007 season
      exhibited a greater diversity. These viruses were A/Solomon Islands/3/2006-like
      and showed several variants. All B isolates were similar to B/Malaysia/2506/2004
      belonging to the B/Victoria/2/87-lineage. Influenza B virus was the dominant
      virus in Europe in the 2005/2006 season and accounted for the 20% of total
      detections in Lombardy. Overall, the viruses studied presented heterogeneity in
      their HA sequences suggesting the circulation of a miscellaneous set of variants
      during the two seasons notwithstanding the medium-low activity of influenza. The
      importance of virological surveillance of influenza viruses is recognized widely
      and the molecular characterization of the viruses, especially in vaccinated
      subjects, is of particular importance to evaluate the introduction and
      circulation of new variants.

PMID- 18814247
TI  - Treatment with silybin-vitamin E-phospholipid complex in patients with hepatitis
      C infection.
AB  - The aim of this study was to evaluate the hepatoprotective and anti-inflammatory
      effects of silybin-phospholipids and vitamin E complex (SPV complex), by
      determining cytokine patterns and various markers of liver disease. Forty
      Caucasian patients with chronic HCV infection were recruited and divided into two
      groups: 30 were treated with SPV complex for 3 months, while the other 10 did not
      receive any treatment. Ten other subjects without HCV infection but with
      staeatosic diagnosis were recruited and treated with SPV complex. Biochemical and
      hepatic principal parameters were investigated at 0 (T0) and 3 months (T3). The
      group of HCV patients treated showed an improvement trend of hepatic indecises
      and viral load, and had a significant and persistent reduction of ALT (P = 0.02)
      and AST serum level (P = 0.01). In this group cytokines showed a statistically
      significant increase of IL-2 (P = 0.03) and IL-6 were significantly reduced (P =
      0.02) at T0 and T3. After the treatment the group of hepatic steatosics showed a
      significant decrease in ALT (P = 0.02), AST (0.008), gammaGT (0.004) alkaline
      phosphatase (0.05), total cholesterol (P = 0.03), fasting glucose (P = 0.008),
      insulinemia (0.0006), HOMA value (0.002) and C-reactive protein (CRP; 0.04).
      There was a significant reduction of IFN-gamma, TNF-alpha, and IL-6 (P = 0.02,
      0.05 and 0.04, respectively). The data suggest that the SPV complex exerts
      hepatoprotective, anti-inflammatory and antifibrotic effects. This new compound
      may therefore be useful in clinical practice in patients with chronic hepatitis C
      who cannot undergo conventional antiviral therapy.

PMID- 18814248
TI  - A pilot study on the distribution of human papillomavirus genotypes and HPV-16
      variants in cervical neoplastic lesions from Ecuadorian women.
AB  - Human papillomaviruses (HPVs) are the cause of cervical intraepithelial neoplasia
      and invasive carcinomas of the uterine cervix. The distribution of specific HPV
      genotypes varies greatly across populations and HPV surveys have been performed
      in different geographical regions in order to apply appropriate vaccine
      strategies. The aim of this study was to determine the spectrum of HPV genotypes
      and HPV-16 variants among women with cervical lesions living in Ecuador. A total
      of 71 cases have been analyzed, including 32 chronic cervicitis, 29 cervical
      intraepithelial neoplasia grade 1, and 10 cervical intraepithelial neoplasia
      grade 2-3. HPV sequences were detected by broad spectrum consensus-primer-pairs
      MY09/MY11 and GP5+/GP6+-based polymerase chain reaction and characterized by
      nucleotide sequence analysis. Overall, 31 (43.7%) cases were HPV positive with
      prevalence rates of 37.5%, 44.8%, and 60% in patients with chronic cervicitis,
      cervical intraepithelial neoplasia grade 1 and cervical intraepithelial neoplasia
      grade 2-3, respectively. Among the positive cases, the most common genotypes were
      HPV 16 (64.5%) and HPV 81 (29%) followed by HPV 31, 53, 56, and 58, in descending
      order of prevalence. Seventeen (85%) HPV-16 isolates were classified as European
      and three (15%) as African-1 variant on the basis of nucleotide signature present
      within the MY09/MY11 L1 sequence. The results suggest that HPV 16 has a very high
      prevalence among women with cervical lesions in Ecuador; therefore, an effective
      HPV-16 based vaccine should prevent the development of cervical cancer in a large
      proportion of Ecuadorian women.

PMID- 18814249
TI  - HTLV-1 infection in blood donors from the Western Brazilian Amazon region:
      seroprevalence and molecular study of viral isolates.
AB  - To determine the seroprevalence of HTLV-1 in Brazil, and to review the virus
      molecular epidemiology in this Amazon population (Rio Branco-Acre), 219 blood
      donors were screened for HTLV-1. Only one case of infection (0.46%
      seroprevalence) was detected during July 2004 screening at the Acre Hospital
      Foundation (FUNDACRE). Neighbor-joining and Maximum Likelihood phylogenetic
      analyses of two (n = 2) complete LTR region sequences were performed with the
      PAUP* software. Since the HTLV-1 envelope surface (gp46) and transmembrane (gp21)
      glycoproteins are important for virus fitness, three envelope glycoproteins
      sequences (n = 3) were analyzed using the Prosite tool to determinate potential
      protein sites. Phylogenetic analysis demonstrated that the new isolate described
      in this study, and the unpublished LTR strain described in a previous report
      belong to the Transcontinental subgroup of the Cosmopolitan subtype, inside the
      Latin American cluster. A similar result was obtained when submitting, to the
      Automated Genotyping System, three LTR partial sequences from a previous study of
      the seroprevalence of HTLV-1 in the same Amazon population. In all analyzed env
      sequences, the potential protein site was found: two PKC phosphorylation sites at
      amino acid (aa) positions 310-312 and 342-344, one CK2 phosphorylation site at
      194-197aa, three N-glycosylation sites at 222-225aa, 244-247aa and 272-275aa, and
      a single N-myristylation site at 327-338aa. In conclusion, potential protein
      sites described in HTLV-1 gp46 and gp21 confirm the presence of conserved sites
      in the HTLV-1 envelope proteins, likewise phylogenetic analysis suggests a
      possible recent introduction of the virus into North Brazil.

PMID- 18814250
TI  - Emergence of the GII4/2006b variant and recombinant noroviruses in China.
AB  - Noroviruses are an important cause of acute gastroenteritis. Increasing data
      showed that the GII-4 strains are predominant worldwide and new GII-4 variants
      emerge every 1-2 years causing major epidemics. Surveillance of gastroenteritis
      in hospitalized children under 5 years of age in China is described. Among 1,110
      specimens, 114 (10.3%) were positive for noroviruses, which was higher than
      adenoviruses (7.6%), astroviruses (3.5%), and sapoviruses (0.9%) and only lower
      than group A rotaviruses (40.6%). Thirty-eight of the 114 positive norovirus
      cases were co-infected with other enteric viruses. Five norovirus genotypes (GI
      2, GI-4, GII-3, GII-4, and GII-14) were detected, with GII-4/2006b the most
      predominant type (64.9%). The reported recombinant of GII-3 capsid and GII-4
      polymerase described previously was also detected frequently and a recombinant of
      GII-14 capsid and GII-6 polymerase was found for the first time. This study
      suggests that continual surveillance focusing on strain variation and dynamic
      change is important for understanding the epidemiology and development of a
      strategy for disease control and prevention.

PMID- 18814251
TI  - Tissue persistence of parvovirus B19 genotypes in asymptomatic persons.
AB  - Parvovirus B19 (B19V) can persist in immunocompetent symptomatic and non
      symptomatic individuals, as demonstrated by the finding of viral DNA in different
      tissues, in absence of viremia and of anti-B19V IgM. The spread and the nature of
      this phenomenon have not been clearly determined. In order to investigate the
      frequency of persistence and the tissue distribution of the three genotypes of
      B19V, the viral load of the persistent virus and its expression in the affected
      tissues, 139 tissue samples and 102 sera from 139 asymptomatic individuals have
      been analyzed by consensus PCRs and genotype specific PCRs for B19V detection and
      genotyping. Viral load was measured by real time PCR and viral mRNAs were
      detected by RT-PCR. Altogether, 51% individuals carried B19V DNA, more frequently
      in solid tissues (65%) than in bone marrow (20%). Genotype 1 was found in 28%
      tissue samples, genotype 2 in 68% and genotype 3 in 3% only. Viral load ranged
      from less then 10 copies to 7 x 10(4) copies per 10(6) cells, with the exception
      of two samples of myocardium with about 10(6) copies per 10(6) cells. mRNA of
      capsid proteins was present in two bone marrow samples only. In conclusion, in
      asymptomatic individuals B19V persistence is more common in solid tissues than in
      bone marrow, and genotype 2 persists more frequently than genotype 1. The results
      suggest that the virus persists without replicating, at sub-immunogenic levels.

PMID- 18814252
TI  - Phylogenetic and molecular analysis of HTLV-1 isolates from a medium sized town
      in northern of Brazil: tracing a common origin of the virus from the most endemic
      city in the country.
AB  - Salvador-Bahia has the highest prevalence of HTLV-1 infection in Brazil; about 2%
      of the population is infected. In this city, the prevalence of HTLV in pregnant
      women is 1%. There is no data of the HTLV-1 prevalence in others cities of the
      Bahia's Reconcavo, where the population has similar social and demography
      characteristics to those from Salvador. Our aim was to evaluate the
      seroprevalence of HTLV in pregnant women in Cruz das Almas-Bahia, a medium-sized
      city from the Bahia's Reconcavo. All individuals were tested for HTLV (ELISA) and
      the positive samples were confirmed by Western Blot. Phylogenetic analyses of the
      total LTR region were performed in all positive samples. We tested 408 samples
      (45.4% of the estimate pregnant women population) between June 1st and October
      31, 2005. The prevalence of HTLV-1 infection was 0.98%. In addition, all isolated
      virus were grouped in the subtype HTLV-1a, in the Latin American group. Our
      results suggest that the introduction of HTLV-1 occurred after the slave trade
      into Salvador. In addition, HTLV-1-infection should be screened during the
      pregnancy in women originating from HTLV-1 endemic areas.

PMID- 18814253
TI  - Interferon-alpha therapy does not modulate hepatic expression of classical type I
      interferon inducible genes.
AB  - Hepatitis C virus (HCV) infection is a major cause of chronic liver disease.
      Treatment with interferon-alpha(2) (IFN-alpha(2)) can induce viral clearance and
      marked biochemical and histological improvement. IFN-alpha(2) treatment has been
      shown to stimulate the expression of type I IFN regulated genes in peripheral
      blood mononuclear cells (PBMCs) of hepatitis C patients; however, whether it
      affects hepatic expression remains unknown. This study thus aimed at comparing
      hepatic gene expression with particular emphasis on type I IFN inducible genes in
      patients with chronic hepatitis C before and during an IFN-alpha(2) monotherapy.
      Responsiveness to IFN-alpha(2) therapy was monitored by determining serum and
      hepatic viral load. Differential gene expression analysis was performed by two
      different techniques, namely suppression subtractive hybridization (SSH) and
      differential display (DD). Expression of two prototype type I IFN regulated genes
      was quantified in further PBMC and liver samples. Among different genes found to
      be up-regulated during an effective, that is, virus clearing, IFN-alpha
      treatment, only a single one was identified which can be accounted to type I IFN
      responsive genes. Parallel quantitative real time PCR analyses demonstrated
      significant induction of the type I IFN regulated genes MxA and PKR in PBMC, but
      not in the liver. Taken together, while IFN-alpha treatment leads to the
      induction of type I IFN regulated genes in PBMC, such an induction appears not to
      occur in the liver of hepatitis C patients. The mechanism by which IFN-alpha
      treatment causes viral clearance might be independent of hepatic activation of
      type I IFN regulated genes.

PMID- 18814254
TI  - Functional polymorphism of the promoter region of the prostacyclin synthase gene
      and severity of RSV infection in hospitalized children.
AB  - Prostaglandin I(2) (PGI(2)) protects against RSV-induced illness in mice. A
      variable-number tandem repeat (VNTR) polymorphism has been detected in the
      promoter region of the PGI(2) synthase (PGIS) gene. We sought to determine if
      PGI(2) concentrations or polymorphisms of the PGIS gene correlate with severity
      of RSV lower respiratory tract infections (LRTI) in human infants. VNTR
      polymorphisms were studied in 81 previously healthy children between birth and 12
      months of age who were hospitalized for LRTI due to RSV and 98 healthy adult
      control subjects. The severity of RSV infection was quantified using a clinical
      scoring system, and infant urine samples were collected during the acute illness
      for measurement of the urinary metabolite of PGI(2). There were no significant
      differences in the overall distribution of alleles and genotypes between infants
      with RSV LRTI and the control subjects. The severity of RSV infection
      significantly inversely correlated with urinary PGI(2) metabolite concentrations.
      The urinary PGI(2) metabolite concentration correlated with the number of VNTR.
      The presence of a genotype with a low number VNTR repeats significantly
      correlated with the most severe RSV LRTI, and genotypes with the highest number
      of VNTR correlated with the least severe RSV LRTI. A functional polymorphism in
      the promoter region of the PGIS gene is associated with both significant
      differences in urinary PGI(2) concentrations during RSV LRTI, and severity of RSV
      infection in previously healthy infants.

PMID- 18814255
TI  - Whole genomic characterization of a human rotavirus strain B219 belonging to a
      novel group of the genus Rotavirus.
AB  - Novel rotavirus strains B219 and ADRV-N derived from adult diarrheal cases in
      Bangladesh and China, respectively, are considered to belong to a novel rotavirus
      group (species) distinct from groups A, B, and C, by genetic analysis of five
      viral genes encoding VP6, VP7, NSP1, NSP2, and NSP3. In this study, the
      nucleotide sequences of the remaining six B219 gene segments encoding VP1, VP2,
      VP3, VP4, NSP4, and NSP5 were determined. The nucleotide sequences of the group B
      human rotavirus VP1 and VP3 genes were also determined in order to compare the
      whole genome of B219 with those of group A, B, and C rotavirus genomes. The
      nucleotide and deduced amino acid sequences of all B219 gene segments showed
      considerable identity to the ADRV-N (strain J19) sequences (87.7-94.3% and 88.7
      98.7%, respectively). In contrast, sequence identity to groups A-C rotavirus
      genes was less than 61%. However, functionally important domains and structural
      characteristics in VP1-VP4, NSP4, and NSP5, which are conserved in group A, B, or
      C rotaviruses, were also found in the deduced amino acid sequences of the B219
      proteins. Hence, the basic structures of all B219 viral proteins are considered
      to be similar to those of the known rotavirus groups.

PMID- 18814256
TI  - Natural polymorphisms in HIV-1 protease: impact on effectiveness of a first-line
      lopinavir-containing antiretroviral therapy regimen.
AB  - Mutations on HIV protease lead to resistance to protease inhibitors. However,
      resistance development may be different according to primary, secondary or
      polymorphic mutations. The present study was designed to assess the impact of
      natural protease mutations on the effectiveness of a first-line antiretroviral
      therapy (ART), and secondarily, their effect on the initial viral load (VL). The
      study was conducted in 175 HIV-1-infected patients, who initiated a first-line
      lopinavir/r-containing ART regimen and who had an available genotype resistance
      testing before initiating therapy. We assessed the association between mutations
      (prevalence > or = 10%) and the initial VL. We assessed the association between
      mutations and ART effectiveness using two surrogate markers: the slope of VL
      decrease at 1 month and the time to VL undetectability. For the 175 patients, the
      initial median VL was 4.94 log(10) copies/ml [interquartile range: 4.44-5.47] and
      the initial median CD4 lymphocyte count, 219/microl [129-296]. Eighteen mutations
      had a prevalence > or = 10%. At 1 month, the median VL decrease was 2.35 log(10)
      copies/ml [1.76-2.82]. The median time to VL undetectability was 128 days [91
      196]. No mutation was associated significantly with the initial VL, the slope of
      VL decrease at 1 month or the time to VL undetectability. This study of
      antiretroviral-naive patients showed that protease polymorphisms had no impact on
      the effectiveness of a lopinavir/r-containing ART regimen. However, polymorphisms
      may affect ART effectiveness differently in other populations, such as ART
      experienced patients and/or patients treated with protease inhibitors other than
      the one used here.

PMID- 18814257
TI  - Role of long-term lamivudine treatment of hepatitis B virus recurrence after
      liver transplantation.
AB  - In this study, the long-term (>3 years) efficacy of combination therapy for
      hepatitis B virus (HBV) recurrence and the associated factors were investigated.
      One hundred and sixty-five consecutive HBsAg-positive patients (92 with liver
      cirrhosis, 73 with hepatocellular carcinoma; HCC) who underwent liver
      transplantation were assessed with a median follow-up time of 40 months. One
      hundred and twenty-one patients (121/165, 73.3%) were treated with lamivudine
      before transplantation for a mean of 8.4 months (range 0.1-72 months). The post
      transplantation treatment protocol consisted of a high dose intravenous hepatitis
      B immunoglobulin (HBIg) followed by a low dose intramuscular HBIg and lamivudine
      combination therapy. Seven (4.2%, 7/165) recipients experienced HBV recurrence at
      a median time of 19 months (range 5-36 months) following transplantation. Six of
      seven cases of HBV recurrence were treated with lamivudine before transplantation
      for a median period of 15 months (range 0.6-30 months). Eighteen (24.6%, 18/73)
      patients had HCC recurrences after transplantation. Of the four patients with
      both HCC and HBV recurrence, three experienced HBV recurrence after recurrence of
      HCC. The clinical factor associated with HBV recurrence in the total cohort (n =
      165) was the duration of antiviral treatment (over 6 months) before
      transplantation (P = 0.004). In the HCC group, HCC recurrence after
      transplantation (P = 0.002), tumor burden before transplantation (P = 0.005), and
      postoperative adjuvant chemotherapy (P = 0.002), were additional factors for HBV
      recurrence. Combination therapy of HBIg and antiviral drugs was effective over 3
      years regardless of the pretransplantation viral load. However, the possible
      recurrence of HBV needs to be monitored cautiously in patients treated with long
      term (over 6 months) lamivudine.

PMID- 18814258
TI  - Case report: T-cell responses during clearance of Andes virus from blood cells 2
      months after severe hantavirus cardiopulmonary syndrome.
AB  - Hantavirus Cardiopulmonary Syndrome (HCPS) due to Andes virus (ANDV) is endemic
      in Chile and Argentina and currently demonstrates a case-fatality rate of 37% in
      humans. By contrast to the chronically infected rodents, it is believed that ANDV
      in humans is cleared during the acute phase. Moreover, to date, both magnitude
      and quality of human T-cell responses during ANDV infection and clearance are
      unknown. Using IFN-gamma and granzyme B ELISPOT assays as well as flow cytometry,
      we prospectively studied the ANDV-specific T-cell responses in a 56-year-old
      convalescing survivor of severe HCPS, whose blood cells remained PCR-positive for
      ANDV-RNA until day 53 after hospital admission, that is, 67 days after infection
      and 42 days after discharge. PCR-negativity was closely related to the increase
      and function of (Gn(46-60))-specific IFN-gamma(+) granzyme B(+) CD8(+) T-cells,
      but not to neutralizing antibody titers. Concurrently, the phenotype of
      CD45RA(+)CCR7(-) Gn(46-60)-specific T-cells shifted from a CD28(-)CD27(+)
      "intermediate" to a CD28(-) CD27(-) "late" effector memory beyond day 53 after
      hospital admission. This is the first report that shows that ANDV can persist in
      the human hosts for more than 2 months. Moreover, the kinetics of T-cell
      responses during ANDV clearance may indicate a major role of T-cells for
      clearance of ANDV and human immunity to this pathogen.

PMID- 18814259
TI  - Comparing the antibody responses against recombinant hemagglutinin proteins of
      avian influenza A (H5N1) virus expressed in insect cells and bacteria.
AB  - The hemagglutinin (HA) of influenza A virus plays an essential role in mediating
      the entry of the virus into host cells. Here, recombinant full-length HA5 protein
      from a H5N1 isolate (A/chicken/hatay/2004(H5N1)) was expressed and purified from
      the baculovirus-insect cell system. As expected, full-length HA5 elicits strong
      neutralizing antibodies, as evaluated in micro-neutralization tests using HA5
      pseudotyped lentiviral particles. In addition, two fragments of HA5 were
      expressed in bacteria and the N-terminal fragment, covering the ectodomain before
      the HA1/HA2 polybasic cleavage site, was found to elicit neutralizing antibodies.
      But the C-terminal fragment, which covers the remaining portion of the
      ectodomain, did not. Neutralizing titer of the anti-serum against the N-terminal
      fragment is only four times lower than the anti-serum against the full-length HA5
      protein. Using a novel membrane fusion assay, the abilities of these antibodies
      to block membrane fusion were found to correlate well with the neutralization
      activities.

PMID- 18814260
TI  - Molecular characterization of VP6-encoding gene of group A human rotavirus
      samples from central west region of Brazil.
AB  - Group A rotaviruses are the main cause of acute gastroenteritis in children
      worldwide. The intermediate capsid protein VP6 encoded by segment 6 of the dsRNA
      genome is the major structural component of the virus and it is highly antigenic
      and immunogenic. VP6 is responsible for group and subgroup (SG) specificities,
      allowing classification of group A rotavirus into SG I, SG II, SG I + II, and SG
      non-I-non-II. VP6-encoding gene of 154 group A human rotavirus samples of
      different G and P genotypes recovered from children in three cities of Central
      West region of Brazil was amplified by reverse transcription-polymerase chain
      reaction followed by sequencing and phylogenetic analysis. Two distinct genetic
      groups could be recognized: VP6 genogroups I and II. Sequences analysis also
      revealed that all samples identified as VP6 genogroup I were associated with NSP4
      genotype A, whereas samples identified as VP6 genogroup II were associated with
      NSP4 genotype B. This is the first study in Central West region regarding genetic
      variability of the VP6 gene. Further molecular surveillance of rotavirus strains
      is needed to understand better the occurrence of VP6 gene diversity in Brazil and
      the significance of VP6 for the control and prevention of rotavirus
      gastroenteritis.

PMID- 18814261
TI  - Absence of transmission of potentially xenotic viruses in a prospective pig to
      primate islet xenotransplantation study.
AB  - Shortage of human donor organs for transplantation has prompted usage of animals
      as an alternative donor source. Pigs are the most acceptable candidate animals
      but issues of xenozoonoses remain. Despite careful monitoring of designated
      pathogen free pigs there is still a risk that their tissues may carry infectious
      agents. Thus xenotransplantation requires extensive pre-clinical study on safety
      of the graft especially for those viruses that are either potentially oncogenic
      and/or immunosuppressive, or can establish persistent infection. A prospective
      pig-to-primate islet xenotransplantation study was performed which includes
      monitoring for potentially xenotic viruses namely porcine endogenous retrovirus
      (PERV), porcine cytomegalovirus (PCMV), porcine lymphotropic herpesvirus (PLHV),
      and porcine circovirus (PCV) using both molecular diagnostic-PCR and RT-PCR and
      serology methods. There was no evidence of pig virus transmission into primate
      recipients. This preclinical study underlines the information concerning viral
      safety of islet cell xenograft in pig-to-primate xenotransplantation.

PMID- 18814262
TI  - Family history of cancer: pooled analysis in the International Head and Neck
      Cancer Epidemiology Consortium.
AB  - Alcohol and tobacco consumption are well-recognized risk factors for head and
      neck cancer (HNC). Evidence suggests that genetic predisposition may also play a
      role. Only a few epidemiologic studies, however, have considered the relation
      between HNC risk and family history of HNC and other cancers. We pooled
      individual-level data across 12 case-control studies including 8,967 HNC cases
      and 13,627 controls. We obtained pooled odds ratios (OR) using fixed and random
      effect models and adjusting for potential confounding factors. All statistical
      tests were two-sided. A family history of HNC in first-degree relatives increased
      the risk of HNC (OR=1.7, 95% confidence interval, CI, 1.2-2.3). The risk was
      higher when the affected relative was a sibling (OR=2.2, 95% CI 1.6-3.1) rather
      than a parent (OR=1.5, 95% CI 1.1-1.8) and for more distal HNC anatomic sites
      (hypopharynx and larynx). The risk was also higher, or limited to, in subjects
      exposed to tobacco. The OR rose to 7.2 (95% CI 5.5-9.5) among subjects with
      family history, who were alcohol and tobacco users. A weak but significant
      association (OR=1.1, 95% CI 1.0-1.2) emerged for family history of other tobacco
      related neoplasms, particularly with laryngeal cancer (OR=1.3, 95% CI 1.1-1.5).
      No association was observed for family history of nontobacco-related neoplasms
      and the risk of HNC (OR=1.0, 95% CI 0.9-1.1). Familial factors play a role in the
      etiology of HNC. In both subjects with and without family history of HNC,
      avoidance of tobacco and alcohol exposure may be the best way to avoid HNC.

PMID- 18814263
TI  - A prospective analysis of the association between dietary fiber intake and
      prostate cancer risk in EPIC.
AB  - Few studies have examined the association between dietary fiber intake and
      prostate cancer risk. We evaluated the association between dietary fiber intake
      and the risk of prostate cancer among 142,590 men in the European Prospective
      Investigation into Cancer and Nutrition (EPIC). Consumption of dietary fiber
      (total, cereal, fruit and vegetable fiber) was estimated by validated dietary
      questionnaires and calibrated using 24-hr dietary recalls. Incidence rate ratios
      were estimated using Cox regression and adjusted for potential confounding
      factors. During an average of 8.7 years follow-up, prostate cancer was diagnosed
      in 2,747 men. Overall, there was no association between dietary fiber intake
      (total, cereal, fruit or vegetable fiber) and prostate cancer risk, although
      calibrated intakes of total fiber and fruit fiber were associated with
      nonstatistically significant reductions in risk. There was no association between
      fiber derived from cereals or vegetables and risk and no evidence for
      heterogeneity in any of the risk estimates by stage or grade of disease. Our
      results suggest that dietary fiber intake is not associated with prostate cancer
      risk.

PMID- 18814265
TI  - Cytomics and nanobioengineering.
AB  - The finding that an individual's genome differs as much as by many million
      variants from that of the human reference assembly diminished the great
      enthusiasm that every disease could be predicted based on nucleotide
      polymorphisms. Even individual cells of an organ may be specifically equipped to
      perform specific tasks and that the information of individual cells in a cell
      system is key information to understand function or dysfunction. Therefore,
      cytomics received great attention during the last years as it allows to
      quantitatively and qualitatively analyzing great number of individual cells, cell
      constituents, and of their intracellular and functional interactions in a
      cellular system and also giving the concept of analysis of these data.Exhaustive
      data extraction from multiparametric assays and multiple tests are the
      prerequisite for prediction of drug toxicity. Cytomics, as novel approach for
      unsupervised data analysis give a chance to find the most predictive parameters,
      which describe best the toxicity of a chemical. Cytomics is intrinsically
      connected to drug development and drug discovery.Focused on small structures,
      nanobioengineering is the ideal partner of cytomics, the systems biological
      discipline for cell population analysis. Realizing the idea "from the molecule to
      the patient" develops and offers chemical compounds, proteins, and other
      biomolecules, cells as well as tissues as instruments and products for a wide
      variety of biotechnological and biomedical applications.The integrative
      nanobioengineering combining different disciplines of nanotechnology will promote
      the development of innovative therapies and diagnostic methods. It can improve
      the precision of the measurements with focus on single cell analysis. By
      nanobioengineering and whole body imaging techniques, cytomics covers the field
      from molecules through bacterial cells, eukaryotic tissues, and organs to small
      animal live analysis. Toxicological testing and medical drug development are
      currently strongly broadening. It harbors the promise to substantially impact on
      various fields of biomedicine, drug discovery, and predictive medicine.As the
      number of scientific data is rising exponentially, new data analysis tools and
      strategies like cytomics and nanobioengineering take a lead and get closer to
      application. Bionanoengineering may strongly support the quantitative data
      supply, thus strengthening the rational for cytomics approach.

PMID- 18814264
TI  - Follicular lymphoma B cells induce the conversion of conventional CD4+ T cells to
      T-regulatory cells.
AB  - There has been accumulating evidence that CD4(+)CD25(+) FoxP3 expressing
      regulatory T cells (Treg) are highly concentrated in tumors, thereby fostering an
      immune-privileged microenvironment. Some studies have shown that T-cell receptor
      (TCR) stimulation can convert conventional T cells into Treg. Follicular lymphoma
      (FL) B cells can enhance this Treg conversion. We investigated whether FL tumor B
      cells, as opposed to normal B cells, are unique in their ability to convert
      effector T cells into Treg. We found that tumor B cells alone, without artificial
      TCR stimulation, could induce conventional T cells to express FoxP3 and to
      acquire regulatory function. In contrast to their malignant counterpart, normal B
      cells did not induce Treg conversion. Treg conversion was independent of the T
      cell background, as T cells isolated from FL or normal peripheral blood were
      equally susceptible to being converted by tumor B cells. Our study provides
      evidence for a tumor-specific mechanism by which FL tumor cells promote immune
      escape through the induction of Treg.

PMID- 18814266
TI  - Lovastatin induces the formation of abnormal myelin-like membrane sheets in
      primary oligodendrocytes.
AB  - Statins, well-known inhibitors of cholesterol synthesis and protein
      isoprenylation, have been proposed as therapeutic drugs for multiple sclerosis
      (MS). As lovastatin and simvastatin, which are currently tested for their use in
      MS, can cross the blood-brain barrier, they may affect cellular processes in the
      central nervous system. This is especially relevant with respect to remyelination
      as a proposed additional treatment for MS, because cholesterol is a major
      component of myelin. Here, we show that primary oligodendrocytes, treated with
      lovastatin, form extensive membrane sheets, which contain galactosphingolipids.
      However, these membrane sheets are devoid of the major myelin proteins, myelin
      basic protein (MBP) and proteolipid protein (PLP). Reduced MBP protein expression
      was confirmed by SDS-PAGE and Western blotting, and in situ hybridization
      experiments revealed that lovastatin blocks MBP mRNA transport into
      oligodendrocyte processes. In contrast, PLP expression was only mildly affected
      by lovastatin. However, lovastatin treatment resulted in intracellular
      accumulation of PLP and prevented its translocation to the cell surface.
      Interestingly, another inhibitor of cholesterol synthesis (ro48-8071), which does
      not interfere with isoprenylation, had a similar effect on the localization of
      PLP, but it did not affect MBP expression and localization. These results suggest
      that lovastatin affects PLP transport predominantly by the inhibition of
      cholesterol synthesis, whereas reduced MBP expression is caused by impaired
      isoprenylation. Based on these results we recommend to carefully monitor the
      effect of statins on myelination prior to their use in demyelinating diseases.

PMID- 18814267
TI  - Leptin induces migration and invasion of glioma cells through MMP-13 production.
AB  - Leptin, the product of the obese gene, plays an important role in the regulation
      of body weight by coordinating metabolism, feeding behavior, energy balance, and
      neuroendocrine responses. However, regulation of leptin gene expression in the
      central nervous system is different from that in the adipocytes. In addition,
      leptin has been found in many tumor cell lines and has been shown to have
      mitogenic and angiogenic activity in a number of cell types. Glioma is the most
      common primary adult brain tumor with poor prognosis because of the spreading of
      tumor cell to the other regions of brain easily. Here we found that malignant C6
      glioma cells expressed more leptin and leptin receptors than nonmalignant
      astrocytes. Furthermore, it was found that exogenous application of leptin
      enhanced the migration and invasion of C6 glioma cells. In addition, we found
      that the expression of matrix metalloproteinase-13 (MMP-13) but not of MMP-2 and
      MMP-9 was increased in response to leptin stimulation. The leptin-induced
      increase of cell migration and invasion was antagonized by MMP-13 neutralizing
      antibody or silencing MMP-13. The up-regulation of MMP-13 induced by leptin was
      mainly through p38 MAP kinase and NF-kappaB pathway. In addition, migration-prone
      sublines demonstrate that cells with increasing migration ability had more
      expression of MMP-13 and leptin. Taken together, these results indicate that
      leptin enhanced migration and invasion of C6 glioma cells through the increase of
      MMP-13 production.

PMID- 18814268
TI  - Matrix metalloproteinase-2 is involved in myelination of dorsal root ganglia
      neurons.
AB  - Matrix metalloproteinases (MMPs) comprise a large family of endopeptidases that
      are capable of degrading all extracellular matrix components. There is increasing
      evidence that MMPs are not only involved in tissue destruction but may also exert
      beneficial effects during axonal regeneration and nerve remyelination. Here, we
      provide evidence that MMP-2 (gelatinase A) is associated with the physiological
      process of myelination in the peripheral nervous system (PNS). In a myelinating
      co-culture model of Schwann cells and dorsal root ganglia neurons, MMP-2
      expression correlated with the degree of myelination as determined by
      immunocytochemistry, zymography, and immunosorbent assay. Modulation of MMP-2
      activity by chemical inhibitors led to incomplete and aberrant myelin formation.
      In vivo MMP-2 expression was detected in the cerebrospinal fluid (CSF) of
      patients with Guillain-Barre syndrome as well as in CSF and sural nerve biopsies
      of patients with chronic inflammatory demyelinating polyneuropathy. Our findings
      suggest an important, previously unrecognized role for MMP-2 during myelination
      in the PNS. Endogenous or exogenous modulation of MMP-2 activity may be a
      relevant target to enhance regeneration in demyelinating diseases of the PNS.

PMID- 18814270
TI  - Human herpesvirus 6 integrates within telomeric regions as evidenced by five
      different chromosomal sites.
AB  - Fluorescent in situ hybridization (FISH) was used to investigate the chromosomal
      integration sites of human herpesvirus 6 (HHV-6) in phytohemagglutinin-stimulated
      leukocytes and B lymphocytes from Epstein-Barr virus transformed lymphoblastoid
      cell lines (LCLs). Five different chromosomal integration sites were found in
      nine individuals. Only one site was identified in each individual, each site was
      in the vicinity of the telomeric region and was on either the p or q arm of only
      one of the two chromosome homologues. The sites were 9q34.3, 10q26.3, 11p15.5,
      17p13.3, and 19q 13.4, of which three have not been previously identified. For
      9q34.3 the site of integration was further mapped using a locus-specific probe
      for 9q34.3 together with a pan-telomeric probe and both co-localized with the HHV
      6 signal. Similarly an arm-specific telomeric probe for 19q co-localized with the
      HHV-6 signal. It was therefore concluded that the site of integration is actually
      within the telomere. The number of viral DNA copies/cell was calculated in blood,
      LCL cells and hair follicles and was one or more in every case for each of the
      nine individuals. This result was confirmed by FISH where 100% of cells gave an
      HHV-6 signal. These findings add to previous reports suggesting that integrated
      HHV-6 DNA is found in every cell in the body and transmitted vertically. Finally,
      including our data, worldwide seven different chromosomal sites of HHV-6
      integration have now been identified. Large epidemiological studies of
      chromosomal integration are required to identify further telomeric sites,
      geographical or racial variation and possible clinical consequences.

PMID- 18814269
TI  - Human fetal radial glia cells generate oligodendrocytes in vitro.
AB  - Limited knowledge about human oligodendrogenesis prompted us to explore the
      lineage relationship between cortical radial glia (RG) cells and oligodendrocytes
      (OLs) in the human fetal forebrain. RG cells were isolated from cortical
      ventricular/subventricular zone and their progeny was followed in vitro. One
      portion of RG cells differentiated into cells of OL lineage identified by cell
      type specific antibodies, including platelet-derived growth factor receptor-alpha
      (PDGFRalpha), NG2, O4, myelin basic protein, and myelin oligodendrocyte
      glycoprotein. Moreover, using Cre Lox fate mapping (brain lipid binding protein
      Cre/Floxed-yellow fluorescent protein) we established a direct link between RG
      cells and OL progenitors. In vitro generation of RG-derived O4(+) OL progenitors
      was enhanced by addition of sonic hedgehog (SHH) and reduced by the SHH
      inhibitor, cyclopamine, suggesting the role of SHH signaling in this process. In
      summary, our in vitro experiments revealed that a portion of cortical RG cells
      isolated from human forebrain at the second trimester of gestation generates OL
      progenitors and this suggests a role of SHH in this process.

PMID- 18814271
TI  - Lack of cross-immune reactivity against influenza H5N1 from seasonal influenza
      vaccine in humans.
AB  - In a small pilot study, sera from 10 healthy human volunteers were taken pre
      vaccine, then 1, 3, and 6 months post-seasonal influenza immunization (using the
      2005/2006 Northern hemisphere vaccine: A/New Caledonia/20/99(H1N1)-like,
      A/California/7/2004(H3N2)-like, and B/Shanghai/361/2002-like strains). Eight out
      of 10 subjects demonstrated satisfactory HAI titers (> or = 40) after seasonal
      influenza vaccination between 1 and 6 months post-vaccine. These sera were then
      tested for inhibitory activity against A/HK/483/97 and A/Thailand/1(KAN-1)/04
      H5N1 influenza viruses using standard hemagglutination inhibition and
      microneutralization assays. In contrast to several other studies in both humans
      and animals on the cross-immunity between different influenza A viruses,
      antibodies produced to the influenza A(H1N1) component of the seasonal influenza
      vaccine showed no cross-reactivity to these avian influenza A(H5N1) viruses.
      Possible reasons for this contrasting result are discussed.

PMID- 18814272
TI  - Identification of the novel KI polyomavirus in the respiratory tract of an
      Italian patient.
AB  - Recently, a new human polyomavirus, KIV, was detected in respiratory specimens of
      patients with acute respiratory tract infection. Whether this reflects a causal
      role of the virus in the respiratory tract is still debated. To investigate the
      presence of KIV in respiratory samples of Italian patients and to determine the
      degree of similarity with other known polyomaviruses, 222 respiratory specimens
      collected by general practitioners between 2006 and 2007 were screened. The
      entire VP1 gene region was amplified and sequenced. Maximum Likelihood tree was
      generated by PAUP* software. One out of 222 samples tested was positive for KIV.
      Phylogenetic analysis indicated that this isolate clustered with other KIV
      isolates, while the WUV isolates seem to belong to a different lineage. The
      phylogenetic tree also showed that all other known polyomaviruses are quite
      distant from this isolate. This is the first report describing the presence of
      KIV in the respiratory tract of a 5-year-old Italian child with acute respiratory
      symptoms. Further investigations are needed to establish an etiological link of
      KIV with acute respiratory illness.

PMID- 18814273
TI  - Genome-wide autozygosity mapping in human populations.
AB  - Individuals are frequently observed to have long segments of uninterrupted
      sequences of homozygous markers. One of the major mechanisms that gives rise to
      such long homozygous segments is consanguineous marriages, where parents pass
      shared chromosomal segments to their child. Such chromosomal segments are also
      known as autozygous segments. The clinical evidence that progeny from inbred
      individuals may have reduced health and fitness because of homozygosity of
      recessive alleles is well known. As the length of such homozygous segments
      depends on the degree of parental consanguinity, it would be logical to observe
      shorter homozygous segments in more outbred populations. However, a recent study
      identified long homozygous regions, thus likely to be autozygous segments in the
      HapMap populations. While an abundance of homozygous segments may significantly
      reduce the ability to fine map disease genes using association studies, detecting
      tracts of extended homozygosity related to disease status seems the natural next
      step in genome-wide association studies beyond allele, genotype and haplotype
      association analyses. In this study, we propose a new algorithm to map disease
      related segments based on autozygosity using case-control data. The underlying
      rationale for the proposed method is that shared autozygosity regions that differ
      between diseased and healthy individuals may harbor mutations underlying
      diseases. Specifically, our algorithm uses a sliding-window framework and employs
      a logarithm of the odds score measure of autozygosity coupled with permutation
      based methods to identify disease-related regions. We illustrate the advantage of
      the algorithm with its application to a genome-wide association study on
      Parkinson's disease.

PMID- 18814274
TI  - Sirolimus-eluting stents versus bare-metal stents in patients with in-stent
      restenosis: results of a pooled analysis of two randomized studies.
AB  - BACKGROUND: Treatment of patients with in-stent restenosis (ISR) remains a
      challenge. We sought to compare results of sirolimus-eluting stents (SES) with
      those of bare-metal stents (BMS) in patients with ISR. METHODS: The results
      obtained in the stent arm of two randomized studies were analyzed. The RIBS I
      study (450 patients with ISR) allocated 224 patients to BMS; the RIBS II study
      (150 patients with ISR) allocated 76 patients to SES. Complete 1-year follow-up
      was obtained in all 300 patients treated with stents. RESULTS: Although
      inclusion/exclusion criteria were identical in the two studies, when compared
      with patients in the BMS group, patients in the SES arm had more adverse baseline
      characteristics, more diffuse lesions, and smaller vessels. However, late
      angiographic findings including in-segment recurrent restenosis rate (11 vs. 38%,
      P < 0.001), minimal lumen diameter (2.52 vs. 1.63 mm, P < 0.001), and late loss
      (0.13 vs. 1.04 mm, P < 0.001) were significantly better after SES. The 1-year
      event-free survival was also significantly improved in the SES group (88 vs. 78%,
      P < 0.05), as the result of a lower requirement for repeated revascularizations
      (10.5 vs. 19.6%, P < 0.05). Prespecified subgroup analyses were consistent with
      the main outcome measures. After adjusting for (a) imbalances in baseline
      characteristics (restenosis OR 0.11 [95% confidence interval (CI) 0.03-0.36];
      adverse events hazard ratios (HR) 0.33 [95% CI 0.13-0.84]) and (b) the propensity
      score (restenosis OR 0.08 [95% CI 0.03-0.28]; adverse events HR 0.24 [95% CI 0.09
      0.66]), results of the SES group were superior to those obtained in the BMS
      group. CONCLUSIONS: When compared with BMS, SES improved the long-term clinical
      and angiographic outcome of patients with ISR.

PMID- 18814275
TI  - Interactions with nanoscale topography: adhesion quantification and signal
      transduction in cells of osteogenic and multipotent lineage.
AB  - Polymeric medical devices widely used in orthopedic surgery play key roles in
      fracture fixation and orthopedic implant design. Topographical modification and
      surface micro-roughness of these devices regulate cellular adhesion, a process
      fundamental in the initiation of osteoinduction and osteogenesis. Advances in
      fabrication techniques have evolved the field of surface modification; in
      particular, nanotechnology has allowed the development of nanoscale substrates
      for the investigation into cell-nanofeature interactions. In this study human
      osteoblasts (HOBs) were cultured on ordered nanoscale pits and random nano
      "craters" and "islands". Adhesion subtypes were quantified by immunofluorescent
      microscopy and cell-substrate interactions investigated via immuno-scanning
      electron microscopy. To investigate the effects of these substrates on cellular
      function 1.7 k microarray analysis was used to establish gene profiles of
      enriched STRO-1+ progenitor cell populations cultured on these nanotopographies.
      Nanotopographies affected the formation of adhesions on experimental substrates.
      Adhesion formation was prominent on planar control substrates and reduced on
      nanocrater and nanoisland topographies; nanopits, however, were shown to inhibit
      directly the formation of large adhesions. STRO-1+ progenitor cells cultured on
      experimental substrates revealed significant changes in genetic expression. This
      study implicates nanotopographical modification as a significant modulator of
      osteoblast adhesion and cellular function in mesenchymal populations.

PMID- 18814276
TI  - Preliminary in vivo evaluation of the protein transduction domain-modified
      ATTEMPTS approach in enhancing asparaginase therapy.
AB  - Asparaginase (ASNase) is an enzyme drug presently approved for the induction of
      remission in the treatment of patients with acute lymphoblastic leukemia (ALL).
      The cytotoxic effect of ASNase is derived from its ability to deplete asparagine,
      an essential amino acid required by certain types of leukemia cells for protein
      synthesis and survival. Despite its efficacy in enhancing disease remission rate
      and prolonging complete remission duration in ALL patients, ASNase therapy is
      nevertheless confounded by a number of serious toxic effects, particularly to
      organs associated with high protein production (e.g., liver, pancreas), due to
      the systemic depletion of asparagine. Presented herein is a modified version of
      our previously established ATTEMPTS protein delivery system that carries the
      potential to permit a tumor specific, intracellular delivery of ASNase, thereby
      allowing for a significant reduction of ASNase-induced systemic toxicity. In a
      previous paper, we already demonstrated the in vitro feasibility of this
      heparin/protamine-regulated, TAT-mediated system in delivering ASNase directly
      into ASNase-sensitive murine lymphoma cells. In this article, we further
      validated the in vivo applicability of this system in animals harboring ASNase
      encapsulated L5178Y lymphoma cells. Preliminary results showed that animals
      inoculated with L5178Y cells containing TAT-ASNase exhibited an extended survival
      rate of approximately 13% over those harboring L5178Y cells without the
      encapsulation of ASNase. Furthermore, the TAT-ASNase-treated mice also displayed
      a significantly improved hematological and liver histological status than the
      control groups. These findings bring promise to the use of the modified ATTEMPTS
      delivery system in achieving enhanced ASNase therapy.

PMID- 18814277
TI  - Cancer-retina antigens as potential paraneoplastic antigens in melanoma
      associated retinopathy.
AB  - Melanoma-associated retinopathy is a rare paraneoplastic neurological syndrome
      characterized by retinopathy in melanoma patients. The main photoreceptor
      proteins have been found to be expressed as cancer-retina antigens in melanoma.
      Here we present evidence that these can function as paraneoplastic antigens in
      melanoma-associated retinopathy. Sera and one tumor cell line of such patients
      were studied and ret-transgenic mice spontaneously developing melanoma were used
      as a murine model for melanoma-associated retinopathy. Splenocytes and sera were
      used for adoptive transfer from tumor-bearing or control mice to wild-type mice.
      Retinopathy was investigated in mice by funduscopy, electroretinography and eye
      histology. Expression of photoreceptor proteins and autoantibodies against
      arrestin and transducin were detected in melanoma-associated retinopathy
      patients. In tumor-bearing ret-transgenic mice, retinopathy was frequently
      (13/15) detected by electroretinogram and eye histology. These pathological
      changes were manifested in degenerations of photoreceptors, bipolar cells and
      pigment epithelium as well as retinal detachment. Mostly these defects were
      combined. Cancer-retina antigens were expressed in tumors of these mice, and
      autoantibodies against arrestin were revealed in some of their sera. Adoptive
      transfer of splenocytes and sera from tumor-bearing into wild-type mice led to
      the induction of retinopathy in 4/16 animals. We suggest that melanoma-associated
      retinopathy can be mediated by humoral and/or cellular immune responses against a
      number of cancer-retina antigens which may function as paraneoplastic antigens in
      melanoma-associated retinopathy.

PMID- 18814278
TI  - Correlated waves of actin filaments and PIP3 in Dictyostelium cells.
AB  - Chemotaxis-deficient amiB-null mutant Dictyostelium cells show two distinct
      movements: (1) they extend protrusions randomly without net displacements; (2)
      they migrate persistently and unidirectionally in a keratocyte-like manner. Here,
      we monitored the intracellular distribution of phosphatidylinositol (3,4,5)
      trisphosphate (PIP(3)) to gain insight into roles PIP(3) plays in those
      spontaneous motilities. In keratocyte-like cells, PIP(3) showed convex
      distribution over the basal membrane, with no anterior enrichment. In stalled
      cells, as well as in wild type cells, PIP(3) repeated wave-like changes,
      including emergence, expansion and disappearance, on the basal membrane. The
      waves induced lamellipodia when they approached the cell edge, and the advancing
      speed of the waves was comparable to the migration speed of the keratocyte-like
      cells. LY294002, an inhibitor of PI3 kinase, abolished PIP(3) waves in stalled
      cells and stopped keratocyte-like cells. These results together suggested that
      keratocyte-like cells are "surfing" on the PIP(3) waves by coupling steady
      lamellipodial protrusions to the PIP(3) waves. Simultaneous live observation of
      actin filaments and PIP(3) in wild type or stalled amiB(-) cells indicated that
      the PIP(3) waves were correlated with wave-like distributions of actin filaments.
      Most notably, PIP(3) waves often followed actin waves, suggesting that PIP(3)
      induces local depolymerization of actin filaments. Consistent with this idea,
      cortical accumulation of PIP(3) was often correlated with local retraction of the
      periphery. We propose that the waves of PIP(3) and actin filaments are loosely
      coupled with each other and play important roles in generating spontaneous cell
      polarity.

PMID- 18814279
TI  - Imatinib mesylate suppresses bone metastases of breast cancer by inhibiting
      osteoclasts through the blockade of c-Fms signals.
AB  - Imatinib mesylate (imatinib) is a potent and selective inhibitor of the tyrosine
      kinases, Bcr-Abl, c-Kit and platelet-derived growth factor receptors (PDGFRs).
      Recently, it has been reported that imatinib also targets the macrophage colony
      stimulating factor (M-CSF) receptor c-Fms. M-CSF signals are essential for the
      differentiation of osteoclasts. Bone metastases of breast cancer are frequently
      associated with osteoclastic bone destruction. Furthermore, several lines of
      evidence suggest that osteoclasts play central roles in the development and
      progression of bone metastases. Thus, in the present study, we examined the
      effects of imatinib on bone metastases of breast cancer. Coimmunoprecipitation
      assays showed that imatinib inhibited the M-CSF-induced phosphorylation of c-Fms
      in osteoclast precursor cells as well as the PDGF-induced PDGFR phosphorylation
      in MDA-MB-231 human breast cancer cells. Imatinib also markedly reduced
      osteoclast formation in vitro. In contrast, those concentrations of imatinib did
      not affect osteoblast differentiation. We then examined the effects of imatinib
      on bone metastases of MDA-MB-231 cells in a nude mouse model. Radiographic and
      histomorphometric analyses demonstrated that imatinib significantly decreased
      bone metastases associated with the reduced number of osteoclasts. In support of
      the notion that the inhibition of c-Fms acts to suppress the development of bone
      metastases, we found that a specific inhibitor of c-Fms Ki20227 also decreased
      bone metastases. In conclusion, these results collectively suggest that imatinib
      reduced bone metastases, at least in part, by inhibiting osteoclastic bone
      destruction through the blockade of c-Fms signals. Our results also suggest that
      imatinib may have a protective effect against cancer treatment-induced bone loss.

PMID- 18814280
TI  - Phosphoglycerate kinase 1-overexpressing lung cancer cells reduce cyclooxygenase
      2 expression and promote anti-tumor immunity in vivo.
AB  - In addition to the known function in the glycolytic pathway, phosphoglycerate
      kinase 1 (PGK-1) promotes reduction of plasmin disulfide bonds leading to
      angiostatin formation and inhibition of tumor angiogenesis. In this study, the
      effects of PGK-1 on anti- tumor immunity against lung cancer were evaluated using
      the Tet-Off control of PGK-1 expression in the Lewis lung carcinoma (LLC-1).
      There was no significant difference in cell proliferation between parental LLC-1
      and LLC-1 transduced with PGK-1 (PGK-LLC-1). However, expression of PGK-1 was
      found to limit tumor growth in mice subcutaneously injected with the cell lines
      and tumor growth was restored after doxycycline treatment. In addition, the cell
      invasion ability of PGK-LLC-1 became weaker than that of LLC-1. Expressions of
      COX-2, TGF-beta1 and PGE2 were all found to be down-regulated in PGK-LLC-1. PGK
      LLC-1 cells treated with doxycycline recovered their COX-2 protein expression. In
      the presence of conditioned medium from PGK-LLC-1, the endothelial cell migration
      was reduced. Moreover, PGK-LLC-1 also stimulated T lymphocytes to express higher
      levels of Th1 cytokine (IFN-gamma) and lower levels of IL-10 in comparison with
      parental LLC-1. PGK-LLC-1 cells restored the growth rate in immunodeficient mice
      when compared with the growth rate in normal mice. In the tissue sections,
      reduced COX-2 expressions and marked infiltrated CD3 T lymphocytes were observed
      in the PGK-LLC-1 injected group. These findings indicate that overexpression of
      PGK-1 in LLC-1 reduces the COX-2 expression, and, in turn, affect PGE2, cell
      invasion, angiogenesis, and the immune functions, and finally inhibit the tumor
      progression.

PMID- 18814281
TI  - Oncogenic NRAS has multiple effects on the malignant phenotype of human melanoma
      cells cultured in vitro.
AB  - Activating mutations in the NRAS gene, which occur predominantly in codon 61
      (Q61R, Q61K) are among the most common genetic events in malignant melanoma. NRAS
      protein with oncogenic codon 61 mutations may therefore be good therapeutic
      targets. In the present study, we used gene expression profiling as a method for
      global characterization of gene expression alterations that resulted from
      treatment of melanoma cells with siRNA specifically targeting NRAS(Q61R). Sixteen
      probe sets representing 15 unique genes were identified whose expression was
      significantly altered by siRNA against NRAS(Q61R) in 2 melanoma cell lines. The
      genes with altered expression are involved in several functions, including
      modulation of cell growth, invasion and migration. The results suggest that
      downregulation of cyclin E2 and cyclin D1 and also upregulation of the negative
      cell-cycle regulator HBP1 in NRAS(Q61R) knockdown cells contribute to the
      inhibition of cell proliferation. Furthermore, suppression of oncogenic NRAS
      results in reduced migration and invasion, which is accompanied by downregulation
      of EphA2 (a receptor tyrosine kinase), uPAR (urokinase receptor) and cytoskeleton
      proteins such as leupaxin, paxillin and vinculin. These studies support the
      concept that suppression of oncogenic NRAS by siRNA can induce growth arrest and
      inhibit invasion of human melanoma cells by modulating the levels of these gene
      products.

PMID- 18814282
TI  - Quality assessment of cross-species hybridization of CHO transcriptome on a mouse
      DNA oligo microarray.
AB  - DNA microarray technology has been widely utilized for species with extensive
      genome sequence information available. Given the limited genomic information
      pertaining to Chinese hamster ovary (CHO) cell line, cross-species hybridization
      using mouse microarrays provides a viable alternative. In this study, the utility
      of mouse Affymetrix microarrays for transcriptome profiling in CHO cells was
      assessed by hybridizing identical sets of cRNA samples from CHO cells on both
      mouse and CHO Affymetrix microarrays. Expression level measured by probe sets for
      orthologous transcripts on the two microarrays was compared. Only a fraction of
      the orthologous probes which detected expression calls in same species
      hybridization were similarly called present in cross species hybridization. In
      further analysis at the 25-mer probe level, it was revealed that specific
      hybridization signals were detectable by the subset of mouse probes that have a
      high degree of homology to the corresponding CHO sequences. The feasibility of
      cross species hybridization for quantifying the extent of differential expression
      was assessed by comparing transcript levels of CHO cells cultivated with and
      without sodium butyrate. While same species hybridization gave consistent degree
      of differential expression calls in replicated runs, a much inferior ability in
      quantifying differential expression was seen with cross species hybridization.
      Our results demonstrate that through detailed analysis of homology at the probe
      pair level, a subset of probes on existing mouse Affymetrix oligo-array can be
      used successfully for transcriptome profiling of CHO cells.

PMID- 18814283
TI  - Cell inactivation and membrane damage after long-term treatments at sub-zero
      temperature in the supercooled and frozen states.
AB  - The survival of cells subjected to cooling at sub-zero temperature is of
      paramount concern in cryobiology. The susceptibility of cells to cryopreservation
      processes, especially freeze-thawing, stimulated considerable interest in better
      understanding the mechanisms leading to cell injury and inactivation. In this
      study, we assessed the viability of cells subjected to cold stress, through long
      term supercooling experiments, versus freeze-thawing stress. The viability of
      Escherichia coli, Saccharomyces cerevisiae, and leukemia cells were assessed over
      time. Supercooled conditions were maintained for 71 days at -10 degrees C, and
      for 4 h at -15 degrees C, and -20 degrees C, without additives or emulsification.
      Results showed that cells could be inactivated by the only action of sub-zero
      temperature, that is, without any water crystallization. The loss of cell
      viability upon exposure to sub-zero temperatures is suggested to be caused by
      exposure to cold shock which induced membrane damage. During holding time in the
      supercooled state, elevated membrane permeability results in uncontrolled mass
      transfer to and from the cell maintained at cold conditions and thus leads to a
      loss of viability. With water crystallization, cells shrink suddenly and thus are
      exposed to cold osmotic shock, which is suggested to induce abrupt loss of cell
      viability. During holding time in the frozen state, cells remain suspended in the
      residual unfrozen fraction of the liquid and are exposed to cold stress that
      would cause membrane damage and loss of viability over time. However, the
      severity of such a stress seems to be moderated by the cell type and the
      increased solute concentration in the unfrozen fraction of the cell suspension.

PMID- 18814284
TI  - Case study and application of process analytical technology (PAT) towards
      bioprocessing: II. Use of ultra-performance liquid chromatography (UPLC) for
      making real-time pooling decisions for process chromatography.
AB  - Process analytical technology (PAT) has been gaining a lot of momentum in the
      biopharmaceutical community due to the potential for continuous real-time quality
      assurance resulting in improved operational control and compliance. Two of the
      key goals that have been outlined for PAT are "variability is managed by the
      process" and "product quality attributes can be accurately and reliably predicted
      over the design space established for materials used, process parameters,
      manufacturing, environmental, and other conditions". Recently, we have been
      examining the feasibility of applying different analytical tools for designing
      PAT applications for bioprocessing. We have previously shown that a commercially
      available online high performance liquid chromatography (HPLC) system can be used
      for analysis that can facilitate real-time decisions for column pooling based on
      product quality attributes (Rathore et al., 2008). In this article we test the
      feasibility of using a commercially available ultra- performance liquid
      chromatography (UPLC) system for real-time pooling of process chromatography
      columns. It is demonstrated that the UPLC system offers a feasible approach and
      meets the requirements of a PAT application. While the application presented here
      is of a reversed phase assay, the approach and the hardware can be easily applied
      to other modes of liquid chromatography.

PMID- 18814286
TI  - Selected reviews on mass spectrometric topics--CXXXVII.

PMID- 18814285
TI  - Relationship between pattern of tumor enhancement and clinicopathologic
      characteristics in intrahepatic cholangiocarcinoma.
AB  - AIM: Common enhancement pattern of intrahepatic cholangiocarcinoma (ICC) on
      computed tomography (CT) is that of hypovascular enhancement; however, in some
      cases, tumor shows identical enhancement in the arterial phase to that in
      hepatocellular carcinoma. To identify the specific characteristics of different
      enhancement patterns, we examined the relationship between CT enhancement pattern
      and clinicopathological features or postoperative prognosis. METHOD: Subjects
      were 43 consecutive ICC patients who had undergone hepatectomy. Enhancement
      patterns were divided into two types: hypovascular or delayed enhancement (Type
      A), and early enhancement in the arterial phase (Type B). RESULTS: Type A
      enhancement was observed in 23 patients and Type B in 20. Accompanying chronic
      viral hepatitis was significantly more frequent in Type B than Type A. Well
      differentiated adenocarcinoma was significantly more frequent in Type B than Type
      A. Multiple tumors were significantly more frequent in Type A than Type B.
      Japanese TNM stage I and II was more frequent in patients with Type B than those
      with Type A. Disease-free or overall survival was significantly better in
      patients with Type B than those with Type A. CONCLUSION: Early enhancement in the
      arterial phase might be a useful indicator of lower malignant potential and
      better survival in ICC patients.

PMID- 18814287
TI  - High gas pressure effects on yeast.
AB  - Dried microorganisms are particularly resistant to high hydrostatic pressure
      effects. However, exposure to high pressures of nitrogen proved to be effective
      in inactivating dried yeasts. In this study, we tried to elucidate this mechanism
      on Saccharomyces cerevisiae. High-pressure treatments were performed using
      different inert gases at 150 MPa and 25 degrees C with holding time values up to
      12 months. The influence of cell hydration was also investigated. For fully
      hydrated cells, pressurized gases had little specific effect: cell inactivation
      was mainly due to compression effects. However, dried cells were sensitive to
      high pressure of gases. In this latter case, two inactivation kinetics were
      observed. For holding time up to 1 h, the inactivation rate increased to 4 log
      and was linked to a loss of membrane integrity and the presence of damage on the
      cell wall. In such case cell inactivation would be due to gas sorption and
      desorption phenomena which would rupture dried cells during a fast pressure
      release. Gas sorption would occur in cell lipid phases. For longer holding times,
      the inactivation rate increased more slightly due to compression effects and/or
      to a slower gas sorption. Water therefore played a key role in cell sensitivity
      to fast gas pressure release. Two hypotheses were proposed to explain this
      phenomenon: the rigidity of vitrified dried cells and the presence of glassy
      solid phases which would favor intracellular gas expansion. Our results showed
      that dried microorganisms can be ruptured and inactivated by a fast pressure
      release with gases.

PMID- 18814288
TI  - NS0 cell damage by high gas velocity sparging in protein-free and cholesterol
      free cultures.
AB  - Recent developments in high cell density and high productivity fed-batch animal
      cell cultures have placed a high demand on oxygenation and carbon dioxide removal
      in bioreactors. The high oxygen demand is often met by increasing agitation and
      sparging rates of air/O2 in the bioreactors. However, as we demonstrate in this
      study, an increase of gas sparging can result in cell damage at the sparger site
      due to high gas entrance velocities. Previous studies have showed that gas bubble
      breakup at the culture surface was primarily responsible for cell damage in
      sparged bioreactors. Such cell damage can be reduced by use of surfactants such
      as Pluronic F-68 in the culture. In our results, where NS0 cells were grown in a
      protein-free and cholesterol-free medium containing 0.5 g/L Pluronic F-68, high
      gas entrance velocity at the sparger site was observed as the second mechanism
      for cell damage. Experiments were performed in scaled-down spinners to model the
      effect of hydrodynamic force resulting from high gas velocities on antibody
      producing NS0 cells. Cell growth and cell death were described by first-order
      kinetics. Cell death rate constant increased significantly from 0.04 to 0.18 day(
      1) with increasing gas entrance velocity from 2.3 to 82.9 m/s at the sparger
      site. The critical gas entrance velocity for the NS0 cell line studied was found
      to be approximately 30 m/s; velocities greater than 30 m/s caused cell damage
      which resulted in reduced viability and consequently reduced antibody production.
      Observations from a second cholesterol-independent NS0 cell line confirmed the
      occurrence of cell damage due to high gas velocities. Increasing the
      concentration of Pluronic F-68 from 0.5 to 2 g/L had no additional protective
      effect on cell damage associated with high gas velocity at the sparger. The
      results of gas velocity analysis for cell damage have been applied in two case
      studies of large-scale antibody manufacturing. The first is a troubleshooting
      study for antibody production carried out in a 600 L bioreactor, and the second
      is the development of a gas sparger design for a large bioreactor scale (e.g.,
      10,000 L) for antibody manufacturing.

PMID- 18814289
TI  - Engineered enzymes for chemical production.
AB  - In order to enable competitive manufacturing routes, most biocatalysts must be
      tailor-made for their processes. Enzymes from nature rarely have the combined
      properties necessary for industrial chemical production such as high activity and
      selectivity on non-natural substrates and toleration of high concentrations of
      organic media over the wide range of conditions (decreasing substrate, increasing
      product concentrations, solvents, etc.,) that will be present over the course of
      a manufacturing process. With the advances in protein engineering technologies, a
      variety of enzyme properties can be altered simultaneously, if the appropriate
      screening parameters are employed. Here we discuss the process of directed
      evolution for the generation of commercially viable biocatalysts for the
      production of fine chemicals, and how novel approaches have helped to overcome
      some of the challenges.

PMID- 18814290
TI  - Anaerobic methanethiol degradation and methanogenic community analysis in an
      alkaline (pH 10) biological process for liquefied petroleum gas desulfurization.
AB  - Anaerobic methanethiol (MT) degradation by mesophilic (30 degrees C) alkaliphilic
      (pH 10) communities was studied in a lab-scale Upflow Anaerobic Sludge Bed (UASB)
      reactor inoculated with a mixture of sediments from the Wadden Sea (The
      Netherlands), Soap Lake (Central Washington), and Russian soda lakes. MT
      degradation started after 32 days of incubation. During the first 252 days,
      complete degradation was achieved till a volumetric loading rate of 7.5 mmol
      MT/L/day, and sulfide, methane, and carbon dioxide were the main reaction
      products. Temporary inhibition of MT degradation occurred after MT peak loads and
      in the presence of dimethyl disulfide (DMDS), which is the autooxidation product
      of MT. From day 252 onwards, methanol was dosed to the reactor as co-substrate at
      a loading rate of 3-6 mmol/L/day to stimulate growth of methylotrophic
      methanogens. Methanol was completely degraded and also a complete MT degradation
      was achieved till a volumetric loading rate of 13 mmol MT/L/day (0.77 mmol
      MT/gVSS/day). However, from day 354 till the end of the experimental run (day
      365), acetate was formed and MT was not completely degraded anymore, indicating
      that methanol-degrading homoacetogenic bacteria had partially outcompeted the
      methanogenic MT-degrading archea. The archeal community in the reactor sludge was
      analyzed by DGGE and sequencing of 16S rRNA genes. The methanogenic archea
      responsible for the degradation of MT in the reactor were related to Methanolobus
      oregonensis. A pure culture, named strain SODA, was obtained by serial dilutions
      in medium containing both trimethyl amine and dimethyl sulfide (DMS). Strain SODA
      degraded MT, DMS, trimethyl amine, and methanol. Flow sheet simulations revealed
      that for sufficient MT removal from liquefied petroleum gas, the extraction and
      biological degradation process should be operated above pH 9.

PMID- 18814291
TI  - Development and validation of a novel bioreactor system for load- and perfusion
      controlled tissue engineering of chondrocyte-constructs.
AB  - Osteoarthritis is a severe socio-economical disease, for which a suitable
      treatment modality does not exist. Tissue engineering of cartilage transplants is
      the most promising method to treat focal cartilage defects. However, current
      culturing procedures do not yet meet the requirements for clinical
      implementation. This article presents a novel bioreactor device for the
      functional tissue engineering of articular cartilage which enables cyclic
      mechanical loading combined with medium perfusion over long periods of time,
      under controlled cultivation and stimulation conditions whilst ensuring system
      sterility. The closed bioreactor consists of a small, perfused, autoclavable,
      twin chamber culture device with a contactless actuator for mechanical loading.
      Uni-axial loading is guided by externally applied magnetic fields with real-time
      feedback-control from a platform load cell and an inductive proximity sensor.
      This precise measurement allows the development of the mechanical properties of
      the cultured tissue to be monitored in real-time. This is an essential step
      towards clinical implementation, as it allows accounting for differences in the
      culture procedure induced by patient-variability. This article describes, based
      on standard agarose hydrogels of 3 mm height and 10 mm diameter, the technical
      concept, implementation, scalability, reproducibility, precision, and the
      calibration procedures of the whole bioreactor instrument. Particular attention
      is given to the contactless loading system by which chondrocyte scaffolds can be
      compressed at defined loading frequencies and magnitudes, whilst maintaining an
      aseptic cultivation procedure. In a "proof of principle" experiment, chondrocyte
      seeded agarose gels were cultured for 21 days in the bioreactor system.
      Intermittent medium perfusion at a steady flow rate (0.5 mL/min) was applied.
      Sterility and cell viability (ds-DNA quantification and fluorometric live/dead
      staining) were preserved in the system. Flow induced shear stress stimulated sGAG
      (sulfated glycosaminoglycan) content (DMMB assay) after 21 days, which was
      confirmed by histological staining of Alcian blue and by immunostaining of
      Aggrecan. Experimental data on mechanotransduction and long-term studies on the
      beneficial effects of combined perfusion and different mechanical loading
      patterns on chondrocyte seeded scaffolds will be published separately.

PMID- 18814292
TI  - Modified Escherichia coli B (BL21), a superior producer of plasmid DNA compared
      with Escherichia coli K (DH5alpha).
AB  - Plasmid DNA (pDNA) is an emerging experimental vaccine, produced in E. coli,
      initially targeted for viral diseases. Unlike traditional protein vaccines whose
      average dose is micrograms, the average dose of pDNA is on the scale of
      milligrams. Production yields are, therefore, important for the future
      development of this vaccine. The E. coli strains currently used for pDNA
      production, JM109 and DH5alpha, are both suitable for production of stable pDNA
      due to the deletion of recA and endA, however, these two E. coli K strains are
      sensitive to growth conditions such as high glucose concentration. On the other
      hand E. coli BL21 is less sensitive to growth conditions than E. coli JM109 or
      DH5alpha, this strain grows to higher densities and due to its active glyoxylate
      shunt and anaplerotic pathways is not sensitive to high glucose concentration.
      This strain is used for recombinant protein production but not for pDNA
      production because of its inability to produce stable pDNA. To adapt E. coli BL21
      for stable pDNA production, the strain was mutated by deleting both recA and
      endA, and a proper growth and production strategy was developed. Production
      values, reaching 2 g/L were obtained using glucose as a carbon source. The
      produced plasmid, which was constructed for HIV clinical study, was found to have
      identical properties to the plasmid currently produced by E. coli DH5alpha.

PMID- 18814293
TI  - Single-cell analysis demonstrates how nutrient deprivation creates apoptotic and
      quiescent cell populations in tumor cylindroids.
AB  - Understanding how quiescent and apoptotic populations form in tumors is necessary
      because these cell types can considerably diminish therapeutic efficacy. Most
      cancer therapeutics are ineffective against quiescent cells because they target
      rapidly proliferating cells. Distinguishing apoptosis is important because
      apoptotic cells are committed to death and do not require treatment. Regrowth of
      quiescent cell can lead to tumor re-occurrence and metastasis, which are the
      leading causes of cancer mortality. We hypothesized that cylindroid cultures and
      acridine orange staining could be used to determine how nutrient diffusion
      creates apoptotic and quiescent regions in tumors. To test this hypothesis we
      developed a microscopy technique to measure cellular DNA and RNA content in
      single cells using thin cylindroids and acridine orange staining. Cell
      classification was compared to flow cytometry of cells grown in defined monolayer
      cultures. The presence of apoptosis was confirmed by morphological nuclear
      analysis. The effect of diffusion was determined by varying incubation time,
      cylindroid size, and exposing cylindroids to nutrient-deficient media. Four
      overlapping regions were identified as a function of cylindroid radius: an outer
      viable/quiescent region; a second quiescent/apoptotic region; a third late-stage
      apoptotic region; and an inner dead region. In monolayer cultures the absence of
      glutamine and growth factors induced apoptosis and hypoxia induced quiescence.
      Treating with nutrient-deficient media suggested that cells became quiescent near
      the periphery because of glucose and oxygen limitations, and became apoptotic and
      died further from the edge because of glutamine and growth factor limitations.
      These results show that cellular microenvironments can be identified in
      cylindroids using simple acridine orange staining and that single cell
      fluorescence can be measured in three-dimensional culture. The developed
      techniques will be useful for developing cancer therapies and determining how
      cell death and apoptosis are induced in three-dimensional tumor tissue.

PMID- 18814294
TI  - Convective-diffusive mass transfer of agonist and the intracellular calcium
      response of endothelial cell.
AB  - Endothelial cell layer regulates several crucial physiological processes of the
      vascular system. The mechanism of the response of this cell layer to the flow of
      surrounding fluid is still largely unclear. In the present article, a comparison
      of the available experimental results for the intracellular calcium ion
      concentration and theoretical results for the extra-cellular ATP concentration
      obtained using a convective-diffusive mass transfer model, has been made which
      supports the mass transfer model for the endothelial cell response to the fluid
      flow. The experimental results are in excellent agreement with the calculated
      values assuming the effect of ATP concentration alone.

PMID- 18814295
TI  - Thermostability and molecular encapsulation within an engineered caged protein
      scaffold.
AB  - Self-assembling biological complexes such as viral capsids have been manipulated
      to function in innovative nanotechnology applications. The E2 component of
      pyruvate dehydrogenase from Bacillus stearothermophilus forms a dodecahedral
      complex and potentially provides another platform for these purposes. In this
      investigation, we show that this protein assembly exhibits unusual stability and
      can be modified to encapsulate model drug molecules. To distill the E2 protein
      down to its structural scaffold core, we synthesized a truncated gene optimized
      for expression in Escherichia coli. The correct assembly and dodecahedral
      structure of the resulting scaffold was confirmed with dynamic light scattering
      and transmission electron microscopy. Using circular dichroism and differential
      scanning calorimetry, we found the thermostability of the complex to be unusually
      high, with an onset temperature of unfolding at 81.1 +/- 0.9 degrees C and an
      apparent midpoint unfolding temperature of 91.4 +/- 1.4 degrees C. To evaluate
      the potential of this scaffold for encapsulation of guest molecules, we made
      variants at residues 381 and 239 which altered the physicochemical properties of
      the hollow internal cavity. These mutants, yielding 60 and 120 mutations within
      this cavity, assembled into the correct architecture and exhibited high
      thermostability that was comparable to the wild-type scaffold. To show the
      applicability of this scaffold, two different fluorescent dye molecules were
      covalently coupled to the cysteine mutant at site 381. We demonstrate that these
      mutations can introduce non-native functionality and enable molecular
      encapsulation within the cavity while still retaining the dodecahedral structure.
      The unusually robust nature of this scaffold and its amenability to internal
      changes reveal its potential for nanoscale applications.

PMID- 18814296
TI  - High-efficiency hydrogen production by an anaerobic, thermophilic enrichment
      culture from an Icelandic hot spring.
AB  - Dark fermentative hydrogen production from glucose by a thermophilic culture
      (33HL), enriched from an Icelandic hot spring sediment sample, was studied in two
      continuous-flow, completely stirred tank reactors (CSTR1, CSTR2) and in one semi
      continuous, anaerobic sequencing batch reactor (ASBR) at 58 degrees C. The 33HL
      produced H2 yield (HY) of up to 3.2 mol-H2/mol-glucose along with acetate in
      batch assay. In the CSTR1 with 33HL inoculum, H2 production was unstable. In the
      ASBR, maintained with 33HL, the H2 production enhanced after the addition of 6
      mg/L of FeSO4 x H2O resulting in HY up to 2.51 mol-H2/mol-glucose (H2 production
      rate (HPR) of 7.85 mmol/h/L). The H2 production increase was associated with an
      increase in butyrate production. In the CSTR2, with ASBR inoculum and FeSO4
      supplementation, stable, high-rate H2 production was obtained with HPR up to 45.8
      mmol/h/L (1.1 L/h/L) and HY of 1.54 mol-H2/mol-glucose. The 33HL batch enrichment
      was dominated by bacterial strains closely affiliated with Thermobrachium celere
      (99.8-100%). T. celere affiliated strains, however, did not thrive in the three
      open system bioreactors. Instead, Thermoanaerobacterium aotearoense (98.5-99.6%)
      affiliated strains, producing H2 along with butyrate and acetate, dominated the
      reactor cultures. This culture had higher H2 production efficiency (HY and
      specific HPR) than reported for mesophilic mixed cultures. Further, the
      thermophilic culture readily formed granules in CSTR and ASBR systems. In
      summary, the thermophilic culture as characterized by high H2 production
      efficiency and ready granulation is considered very promising for H2 fermentation
      from carbohydrates.

PMID- 18814297
TI  - Valorization of onion waste and by-products: MCR-ALS applied to reveal the
      compositional profiles of alcoholic fermentations of onion juice monitored by
      near-infrared spectroscopy.
AB  - The overall purpose of the project, of which this study is a part, was to examine
      the feasibility of onion waste as a support-substrate for the profitable
      production of food-grade products. This study focused on the efficient production
      of ethanol from worthless onions by transforming the onion juice into onion
      liquor via alcoholic fermentation with the yeast Saccharomyces cerevisiae. The
      onion bioethanol produced could be later used as a favorable substrate for acetic
      fermentation to finally obtain onion vinegar. Near-infrared spectroscopy (NIRS),
      coupled with the multivariate curve resolution-alternating least squares (MCR
      ALS) method, has been used to reveal the compositional and spectral profiles for
      both substrates and products of alcoholic fermentation runs, that is, total
      sugars, ethanol, and biomass concentration. The ambiguity associated with the ALS
      calculation was resolved by applying suitable inequality and equality
      constraints. The quality of the results provided by the NIR-based MCR-ALS
      methodology adopted was evaluated by several performance indicators, including
      the variance explained by the model, the lack of fit and the agreement between
      the MCR-ALS achieved solution and the results computed by applying previously
      validated PLS reference models. An additional fermentation run was employed to
      test the actual predictive ability of the ALS model developed. For all the
      components resolved in the fermentation system studied (i.e., total sugars,
      ethanol, and biomass), the final model obtained showed a high predictive ability
      and suitable accuracy and precision, both in calibration and external validation,
      confirmed by the very good agreement between the ALS responses and the reference
      values (the coefficient of determination was, in all cases, very close to 1, and
      the statistics confirmed that no significant difference was found between PLS
      reference models and the MCR-ALS methodology applied). Thus, the proven
      reliability of the MCR-ALS model presented in this study, based only on NIR
      measurements, makes it suitable for monitoring of the key species involved in the
      alcoholic fermentation of onion juice, allowing the process to be modeled and
      controlled in real time.

PMID- 18814299
TI  - Protonate3D: assignment of ionization states and hydrogen coordinates to
      macromolecular structures.
AB  - A new method, called Protonate3D, is presented for the automated prediction of
      hydrogen coordinates given the 3D coordinates of the heavy atoms of a
      macromolecular structure. Protonate3D considers side-chain "flip," rotamer,
      tautomer, and ionization states of all chemical groups, ligands, and solvent,
      provided suitable templates are available in a parameter file. The energy model
      includes van der Waals, Coulomb, solvation, rotamer, tautomer, and titration
      effects. The results of computational validation experiments suggest that
      Protonate3D can accurately predict the location of hydrogen atoms in
      macromolecular structures.

PMID- 18814300
TI  - Identification of selectivity-determining residues in cytochrome P450
      monooxygenases: a systematic analysis of the substrate recognition site 5.
AB  - The large and diverse family of cytochrome P450 monooxygenases (CYPs) was
      systematically analyzed to identify selectivity- and specificity-determining
      residues in the substrate recognition site 5, which is located in close vicinity
      to the heme center. A positively charged heme-interacting residue was identified
      in the structures of 29 monooxygenases and in 97.7% of the 6379 CYP sequences
      investigated here. This heme-interacting residue restricts the conformation of
      the substrate recognition site 5 and is preferentially located at position 10 or
      11 after the conserved ExxR motif (in 94.4% of the sequences), in 3.3% of the
      sequences at position 9 or 12. As a result, a classification by the position of
      the heme-interacting residue allows to predict residues that are closest to the
      heme center and restrict its accessibility. In 98.4% of all CYP sequences a
      preferentially hydrophobic residue is located at position 5 after the ExxR motif
      that is predicted to point close to the heme center. Replacing this residue by
      hydrophobic residues of different size has been shown to change substrate
      specificity and regioselectivity for CYPs of different superfamilies. Twenty
      seven percent of all CYPs are predicted to contain a second selectivity
      determining residue at position 9 after the ExxR motif that can be identified by
      the pattern EXXR-X(7)-{P}-x-P-[HKR].

PMID- 18814301
TI  - Crystal structure of an alkaline serine protease from Nesterenkonia sp. defines a
      novel family of secreted bacterial proteases.

PMID- 18814302
TI  - Correspondence to article: Closure of the femoral artery after cardiac
      catheterization--a comparison of Angio-Seal, StarClose, and manual compression.

PMID- 18814304
TI  - Relationships between patient-centered cancer nursing interventions and desired
      health outcomes in the context of the health care system.
AB  - A non-experimental longitudinal prospective study was conducted to examine the
      relationships between patient-centered nursing interventions (PCNIs), system
      characteristics, patient characteristics, and desired health outcomes (DHOs) for
      173 hematology-oncology patients. Forty-nine nurse participants provided system
      characteristics data. Confirmatory factor analyses yielded parsimonious scales to
      operationalize the variables. In the path model, one PCNI-individualization-was
      positively related to three subsequent DHOs: authentic self-representation,
      optimism, and sense of well-being. Two additional PCNIs-responsiveness and
      proficiency-were positively related to subsequent trust in nurses. PCNIs did not
      vary with patient race, ethnicity, age, gender, or educational level. Patient
      centeredness of care for cancer patients may be enhanced by quality improvement
      activities that measure and monitor these PCNIs and resultant outcomes.

PMID- 18814305
TI  - The "icefish paradox." Which is the task of neuroglobin in Antarctic hemoglobin
      less icefish?

PMID- 18814306
TI  - Beyond the nearest-neighbor Zimm-Bragg model for helix-coil transition in
      peptides.
AB  - The nearest-neighbor (micro = 1) variant of the Zimm and Bragg (ZB) model has
      been extensively used to describe the helix-coil transition in biopolymers. In
      this work, we investigate the helix-coil transition for a 21-residue alanine
      peptide (AP) with the ZB model up to fourth nearest neighbor (micro = 1, 2, 3,
      and 4). We use a matrix approach that takes into account combinations of any
      number of helical stretches of any length and therefore gives the exact
      statistical weight of the chain within the assumptions of the ZB model. The
      parameters of the model are determined by fitting the temperature-dependent
      circular dichroism and Fourier transform infrared experimental spectra of the AP.
      All variants of the model fit the experimental data, thus giving similar results
      in terms of the macroscopic observables, such as temperature-dependent fractional
      helicity. However, the resulting microscopic parameters, such as distributions of
      the individual residue helical probabilities and free energy surfaces, vary
      significantly depending on the variant of the model. Overall, the mean residue
      enthalpy and entropy (in the absolute value) both increase with micro, but
      combined yield essentially the same "effective" value of the ZB propagation
      parameters for all micro. Greater helical probabilities for individual residues
      are predicted for larger micro, in particular, near the center of the sequence.
      The ZB nucleation parameters increase with increasing micro, which results in a
      lower free energy barrier to helix nucleation and lower apparent "cooperativity"
      of the transition. The significance of the long-range interactions for the
      predictions of ZB model for helix-coil transition, the calculated model
      parameters and the limitations of the model are discussed.

PMID- 18814307
TI  - Power comparisons between similarity-based multilocus association methods,
      logistic regression, and score tests for haplotypes.
AB  - Recently, a genomic distance-based regression for multilocus associations was
      proposed (Wessel and Schork [2006] Am. J. Hum. Genet. 79:792-806) in which either
      locus or haplotype scoring can be used to measure genetic distance. Although it
      allows various measures of genomic similarity and simultaneous analyses of
      multiple phenotypes, its power relative to other methods for case-control
      analyses is not well known. We compare the power of traditional methods with this
      new distance-based approach, for both locus-scoring and haplotype-scoring
      strategies. We discuss the relative power of these association methods with
      respect to five properties: (1) the marker informativity; (2) the number of
      markers; (3) the causal allele frequency; (4) the preponderance of the most
      common high-risk haplotype; (5) the correlation between the causal single
      nucleotide polymorphism (SNP) and its flanking markers. We found that locus-based
      logistic regression and the global score test for haplotypes suffered from power
      loss when many markers were included in the analyses, due to many degrees of
      freedom. In contrast, the distance-based approach was not as vulnerable to more
      markers or more haplotypes. A genotype counting measure was more sensitive to the
      marker informativity and the correlation between the causal SNP and its flanking
      markers. After examining the impact of the five properties on power, we found
      that on average, the genomic distance-based regression that uses a matching
      measure for diplotypes was the most powerful and robust method among the seven
      methods we compared.

PMID- 18814309
TI  - Modeling and prediction of binding affinities between the human amphiphysin SH3
      domain and its peptide ligands using genetic algorithm-Gaussian processes.
AB  - In this article, we discuss the application of the Gaussian process (GP) and
      other statistical methods (PLS, ANN, and SVM) for the modeling and prediction of
      binding affinities between the human amphiphysin SH3 domain and its peptide
      ligands. Divided physicochemical property scores of amino acids, involving
      significant hydrogen bond, electronic, hydrophobic, and steric properties, was
      used to characterize the peptide structures, and quantitative structure-affinity
      relationship models were then constructed by PLS, ANN, SVM, and GP coupled with
      genetic algorithm-variable selection. The results show that: (i) since the
      significant flexibility and high complexity possessed in polypeptide structures,
      linear PLS method was incapable of fulfilling a satisfying behavior on SH3 domain
      binding peptide dataset; (ii) the overfitting involved in training process has
      decreased the predictive power of ANN model to some extent; (iii) both SVM and GP
      have a good performance for SH3 domain binding peptide dataset. Moreover, by
      combining linear and nonlinear terms in the covariance function, the GP is
      capable of handling linear and nonlinear-hybrid relationship, and which thus
      obtained a more stable and predictable model than SVM. Analyses of GP models
      showed that diversified properties contribute remarkable effect to the
      interactions between the SH3 domain and the peptides. Particularly, steric
      property and hydrophobicity of P(2), electronic property of P(0), and electronic
      property and hydrogen bond property of P(-3) in decapeptide
      (P(4)P(3)P(2)P(1)P(0)P(-1)P(-2)P(-3)P(-4)P(-5)) significantly contribute to the
      binding affinities of SH3 domain-peptide interactions.

PMID- 18814308
TI  - Power consequences of linkage disequilibrium variation between populations.
AB  - We quantify the degree to which LD differences exist in the human genome and
      investigates the consequences that variations in patterns of LD between
      populations can have on the power of case-control or family-trio association
      studies. Although only a small proportion of SNPs show significant LD differences
      (0.8-5%), these can introduce artificial signals of associations and reduce the
      power to detect true associations in case-control designs, even when meta
      analytic approaches are used to account for stratification. We show that
      combining trios from different populations in the presence of significant LD
      differences can adversely affect power even though the number of trios has
      increased. Our results have implications on genetic studies conducted in
      populations with substantial population structure and show that the use of meta
      analytic approaches or family-based designs to protect Type 1 error does not
      prevent loss of power due to differences in LD across populations.

PMID- 18814310
TI  - A novel role for anosmin-1 in the adhesion and migration of oligodendrocyte
      precursors.
AB  - At embryonic stages of development, oligodendrocyte precursors (OPCs) generated
      in the preoptic area colonize the entire optic nerve (ON). Different factors
      controlling migration of ON OPCs have been identified, including secreted growth
      factors, morphogens and guidance cues, as well as cell adhesion molecules. We
      have shown previously that the soluble form of the extracellular matrix (ECM)
      protein anosmin-1, impairs OPC migration induced by FGF-2. In the present work,
      we show that anosmin-1 is expressed by both migrating OPCs and axons of the
      retinal ganglion cells in the embryonic ON. In vitro, we observe that OPC
      migration is strongly impaired by contact with anosmin-1 when used as a substrate
      and, in contrast to previous results, this effect is independent of FGF-2/FGFR1
      signaling. We also show that OPCs preferentially adhere to anosmin-1 when
      compared with other ECM molecules used as substrates, and that when the
      endogenous anosmin-1 expressed by OPCs is blocked, OPC adhesion to all the
      different substrates (including anosmin-1), is significantly reduced. This novel
      effect of anosmin-1 on cell adhesion is also independent of FGF-2/FGFR1. We
      finally demonstrate that the blockade of the endogenous anosmin-1 expressed by
      OPCs impairs their migration. Our data suggest that the endogenous anosmin-1
      expressed by OPCs is necessary for the correct adhesion of these cells to the
      different components of the ECM (including anosmin-1 itself), contributing to the
      migration of these cells.

PMID- 18814311
TI  - New directions and resources in group psychotherapy: introduction to the issue.
AB  - Establishing an evidence-based practice (EBP) is a central byproduct of the ever
      increasing emphasis on accountability in mental health services. Though much has
      been written and developed for individual psychotherapists who wish to develop
      EBPs, there are far fewer resources for group psychotherapists. This article
      introduces a series of articles designed to provide EBPs and resources for group
      psychotherapists. We discuss how therapists can develop and apply the following
      aspects of EBPs: research-supported treatments (RSTs), practice guidelines,
      practice-based evidence, and multicultural competence.

PMID- 18814312
TI  - A clinician's take on evidence-based group psychotherapy: a commentary.
AB  - Each of the articles in this issue of the Journal of Clinical Psychology: In
      Session provides valuable resources to group psychotherapists looking to develop
      an evidence-based practice. This article provides a summary of and commentary on
      this information from a clinician's point of view. I discuss the clinical utility
      of these resources, while acknowledging and addressing the practitioner concerns
      associated with them.

PMID- 18814313
TI  - Patterns of p57Kip2 expression in embryonic rat brain suggest roles in progenitor
      cell cycle exit and neuronal differentiation.
AB  - In developing central nervous system, a variety of mechanisms couple cell cycle
      exit to differentiation during neurogenesis. The cyclin-dependent kinase (CDK)
      inhibitor p57Kip2 controls the transition from proliferation to differentiation
      in many tissues, but roles in developing brain remain uncertain. To characterize
      possible functions, we defined p57Kip2 protein expression in embryonic (E) day
      12.5 to 20.5 rat brains using immunohistochemistry combined with markers of
      proliferation and differentiation. The p57Kip2 was localized primarily in cell
      nuclei and positive cells formed two distinct patterns including wide dispersion
      and laminar aggregation that were brain region-specific. From E12.5 to E16.5,
      p57Kip2 expression was detected mainly in ventricular zone (VZ) and/or mantle
      zone of hippocampus, septum, basal ganglia, thalamus, hypothalamus, midbrain, and
      spinal cord. After E18.5, p57Kip2 was detected in select regions undergoing
      differentiation. The p57Kip2 expression was also compared with regional
      transcription factors, including Ngn2, Nkx2.1, and Pax6. Time course studies
      performed in diencephalon showed that p57Kip2 immunoreactivity colocalized with
      BrdU at 8 hr in nuclei exhibiting the wide dispersion pattern, whereas
      colocalization in the laminar pattern occurred only later. Moreover, p57Kip2
      frequently colocalized with neuronal marker, beta-III tubulin. Finally, we
      characterized relationships of p57Kip2 to CDK inhibitor p27Kip1: in proliferative
      regions, p57Kip2 expression preceded p27Kip1 as cells underwent differentiation,
      though the proteins colocalized in substantial numbers of cells, suggesting
      potentially related yet distinct functions of Cip/Kip family members during
      neurogenesis. Our observations that p57Kip2 exhibits nuclear expression as
      precursors exit the cell cycle and begin expressing neuronal characteristics
      suggests that the CDK inhibitor contributes to regulating the transition from
      proliferation to differentiation during brain development.

PMID- 18814314
TI  - Functional differentiation of a clone resembling embryonic cortical interneuron
      progenitors.
AB  - We have generated clones (L2.3 and RG3.6) of neural progenitors with radial glial
      properties from rat E14.5 cortex that differentiate into astrocytes, neurons, and
      oligodendrocytes. Here, we describe a different clone (L2.2) that gives rise
      exclusively to neurons, but not to glia. Neuronal differentiation of L2.2 cells
      was inhibited by bone morphogenic protein 2 (BMP2) and enhanced by Sonic Hedgehog
      (SHH) similar to cortical interneuron progenitors. Compared with L2.3,
      differentiating L2.2 cells expressed significantly higher levels of mRNAs for
      glutamate decarboxylases (GADs), DLX transcription factors, calretinin,
      calbindin, neuropeptide Y (NPY), and somatostatin. Increased levels of DLX-2,
      GADs, and calretinin proteins were confirmed upon differentiation. L2.2 cells
      differentiated into neurons that fired action potentials in vitro, and their
      electrophysiological differentiation was accelerated and more complete when
      cocultured with developing astroglial cells but not with conditioned medium from
      these cells. The combined results suggest that clone L2.2 resembles GABAergic
      interneuron progenitors in the developing forebrain.

PMID- 18814315
TI  - Organizational effects of maternal testosterone on reproductive behavior of adult
      house sparrows.
AB  - Despite the well-known, long-term, organizational actions of sex steroids on
      phenotypic differences between the sexes, studies of maternal steroids in the
      vertebrate egg have mainly focused on effects seen in early life. Long-term
      organizational effects of yolk hormones on adult behavior and the underlying
      mechanisms that generate them have been largely ignored. Using an experiment in
      which hand-reared house sparrows (Passer domesticus) from testosterone- or
      control-treated eggs were kept under identical conditions, we show that
      testosterone treatment in the egg increased the frequency of aggressive,
      dominance, and sexual behavior of 1-year-old, reproductively competent house
      sparrows. We also show that circulating plasma levels of progesterone,
      testosterone, 5alpha-dihydrotestosterone, and 17beta-estradiol did not differ
      between treatment groups. Thus, a simple change in adult gonadal hormone
      secretion is not the primary physiological cause of long-term effects of maternal
      steroids on adult behavior. Rather, differences in adult behavior caused by
      exposure to yolk testosterone during embryonic development are likely generated
      by organizational modifications of brain function. Furthermore, our data provide
      evidence that hormone-mediated maternal effects are an epigenetic mechanism
      causing intra-sexual variation in adult behavioral phenotype.

PMID- 18814316
TI  - Molecular interactions of isoxazolcurcumin with human serum albumin:
      spectroscopic and molecular modeling studies.
AB  - Curcumin is a nontoxic natural product with diverse pharmacological potencies. We
      report the interaction of a potent synthetic derivative of curcumin,
      isoxazolcurcumin (IOC) with human serum albumin (HSA) using various biophysical
      methods. The observed fluorescence quenching of HSA by IOC is due to a complex
      formation by a static quenching process with a quenching constant of the order of
      10(5) M(-1). The binding affinity and the number of binding sites were obtained
      from a Scatchard analysis. Thermodynamics reveals that the interaction is entropy
      driven with predominantly hydrophobic forces. From the observed Forster-type
      fluorescence resonance energy transfer (FRET), the donor (Trp 214 in HSA) to
      acceptor (IOC) distance is calculated to be 3.2 nm. The conformational changes of
      HSA due to the interaction were investigated qualitatively from synchronous
      fluorescence spectra along with a quantitative estimation of the secondary
      structure from Fourier Transform Infrared (FTIR) and circular dichroism (CD)
      spectroscopies. Molecular docking studies were performed to obtain information on
      the possible residues involved in the interaction process, and changes in
      accessible surface area of the interacting residues were calculated. The
      preferred binding site of IOC was analyzed by ligand displacement experiments
      with 1-anilino-8-naphthalenesulfonate (ANS) and warfarin-bound HSA.

PMID- 18814317
TI  - Anti-biofouling properties of polymers with a carboxybetaine moiety.
AB  - The resistance of random copolymers of BMA and CMB against biofouling was
      evaluated. The amount of proteins adsorbed onto the CMB copolymers was smaller
      than that onto other polymers (non-ionic polymers and copolymers of ordinary
      ionic monomers and BMA) and decreased with an increase in the content of CMB
      residues. Furthermore, there was a dramatic decrease in the number of cells
      (platelets and fibroblasts) that adhered to the CMB copolymers compared with that
      to other polymers. In contrast with this, CMB copolymers were slightly
      perturbative to both complement and coagulation systems. However, the overall
      results suggest that zwitterionic moieties are effective for making polymer
      materials biocompatible due to their excellent anti-biofouling property.

PMID- 18814318
TI  - Biodegradable nanogels prepared by self-assembly of poly(L-lactide)-grafted
      dextran: entrapment and release of proteins.
AB  - We showed previously that poly(L-lactide)-grafted dextran could form
      biodegradable nanogels in water. In this paper, various properties of Dex-g-PLLA
      nanogels were compared with Dex-Chol (dextran-cholesterol conjugate) nanogels to
      investigate the effects of hydrophobic units. Dex-g-PLLA nanogels exhibited
      significantly lower CAC and higher colloidal stability, indicating a strong
      tendency to form nanogels. We prepared lysozyme-loaded Dex-g-PLLA nanogels, and
      they exhibited a sustained release of lysozyme for 1 week without denaturation in
      PBS at 37 degrees C. The Dex-g-PLLA nanogels therefore have great potential as a
      delivery vehicle for therapeutic protein.

PMID- 18814319
TI  - Synergistic effect and hierarchical nanostructure formation in mixing two
      designer lipid-like peptide surfactants Ac-A6D-OH and Ac-A6K-NH2.
AB  - We here report the nanostructures from combinational self-assembly of two
      designer lipid-like peptides Ac-A6D-OH and Ac-A6K-NH2 using dynamic light
      scattering (DLS) and atomic force microscopy (AFM). The synergistic phenomenon is
      observed by measuring the critical aggregation concentrations (CACs) of these two
      mixed peptides, in different molar ratios by DLS. The nanoropes were observed in
      AFM images at a molar ratio of Ac-A6D-OH/Ac-A6K-NH2 = 1:1, and the thin film
      formation with aligned nanoropes is shown at a molar ratio of 2:1. The well
      aligned nanoropes at the molar ratio of Ac-A6D-OH/Ac-A6K-NH2 = 2:1 indicated the
      competition factor between the electrostatic repulsion according to DLVO theory
      and the hydrophobic interaction arising from the long side chains on lysine
      residues. This study will further our understanding for designing new
      nanomaterials based on designer lipid-like peptide surfactants.

PMID- 18814320
TI  - Carbenes stabilized by ylides: pushing the limits.

PMID- 18814321
TI  - Two-component liquid crystals as chiral reaction media: highly enantioselective
      photodimerization of an anthracene derivative driven by the ordered
      microenvironment.

PMID- 18814322
TI  - Calculated Raman optical activity signatures of tryptophan side chains.

PMID- 18814323
TI  - Peptide enrichment and protein fractionation using selective electrophoresis.
AB  - In recent times, the analysis of the peptidome has become increasingly valuable
      to gain a better understanding of the critical roles native peptides play in
      biological processes. Here, we show a technique using a novel electrophoretic
      device named MF10, for the fractionation of proteins and peptides based on size
      and also pH in low volume liquid phase under an electric field. A 1 microM, 7
      protein and peptide standard mix ranging from 1 to 25 kDa has been used to show
      peptide migration into a fraction contained by 1-5 kDa membranes. Simultaneous
      fractionation of the higher mass protein standards to the correct fraction also
      occurred. To assess the MF10's ability to fractionate more complex samples, human
      plasma was used to enrich for the peptidome below 5 kDa in the presence of the
      proteome. Peptide enrichment was achieved while simultaneously fractionating
      higher mass proteins to three other mass restricted fractions. The utility of
      this approach is demonstrated with the identification (with at least 2 ppm mass
      accuracy) of 76 unique peptides, equating to 22 proteins enriched to the 1-5 kDa
      fraction of the MF10.

PMID- 18814324
TI  - Determination of protein and RNA expression levels of common housekeeping genes
      in a mouse model of neurodegeneration.
AB  - The choice of housekeeping proteins or genes for internal standards should be
      made carefully, taking into account the cell and tissue type, the experimental
      conditions, and the healthy/disease state(s) under consideration. Furthermore, as
      the correlation between transcriptional and translational levels of commonly used
      housekeeping genes is often discussed, this study shed light on the
      transcriptional levels of beta-actin and glyceraldehyde-3-phosphate dehydrogenase
      (GAPDH) and the translational levels of beta-actin, GAPDH, and beta-tubulin in an
      amyotrophic lateral sclerosis mouse model.

PMID- 18814325
TI  - Comparative analysis of proteome differential regulation during cell
      dedifferentiation in Arabidopsis.
AB  - Cell dedifferentiation is a cell fate switching process in which differentiated
      cells undergo genome reprogramming to regain the competency of cell division and
      organ regeneration. The molecular mechanism underlying the cell dedifferentiation
      process remains obscure. In this report, we investigate the cell
      dedifferentiation process in Arabidopsis using a shotgun proteomics approach. A
      total of 758 proteins are identified by two or more matched peptides. Comparative
      analyses at four time points using two label-free methods reveal that 193
      proteins display up-regulation and 183 proteins display down-regulation within 48
      h. While the results of the two label-free quantification methods match well with
      each other, comparison with previously published 2-DE gel results reveal that
      label-free quantification results differ substantially from those of the 2-DE
      method for proteins with peptides common to multiple proteins, suggesting a
      limitation of the label-free methods in quantifying proteins with closely related
      family members in complex samples. Our results show that the shotgun approach and
      the traditional 2-DE gel approach complement each other in both protein
      identification and quantification. An interesting observation is that core
      histones and histone variants are subjected to extensive down-regulation,
      indicating that there is a dramatic change in the chromatin during cell
      differentiation.

PMID- 18814326
TI  - Phosphoproteomics, oncogenic signaling and cancer research.
AB  - The past 5 years have seen an explosion of phosphoproteomics methods development.
      In this review, using epidermal growth-factor signaling as a model, we will
      discuss how phosphoproteomics, along with bioinformatics and computational
      modeling, have impacted key aspects of oncogenic signaling such as in the
      temporal fine mapping of phosphorylation events, and the identification of novel
      tyrosine kinase substrates and phosphorylation sites. We submit that the next
      decade will see considerable exploitation of phosphoproteomics in cancer
      research. Such a phenomenon is already happening as exemplified by its use in
      promoting the understanding of the molecular etiology of cancer and target
      directed therapeutics.

PMID- 18814327
TI  - A novel method for isolation of membrane proteins: a baculovirus surface display
      system.
AB  - We have developed a novel baculovirus surface display (BVSD) system for the
      isolation of membrane proteins. We expressed a reporter gene that encoded
      hemagglutinin gene fused in frame with the signal peptide and transmembrane
      domain of the baculovirus gp64 protein, which is displayed on the surface of
      BmNPV virions. The expression of this fusion protein on the virion envelope
      allowed us to develop two methods for isolating membrane proteins. In the first
      method, we isolated proteins directly from the envelope of budding BmNPV virions.
      In the second method, we isolated proteins from cellular membranes that had
      disintegrated due to viral egress. We isolated 6756 proteins. Of these, 1883 have
      sequence similarities to membrane proteins and 1550 proteins are homologous to
      known membrane proteins. This study indicates that membrane proteins can be
      effectively isolated using our BVSD system. Using an analogous method, membrane
      proteins can be isolated from other eukaryotic organisms, including human beings,
      by employing a host cell-specific budding virus.

PMID- 18814328
TI  - Hemocyte-lineage marker proteins in a crustacean, the freshwater crayfish,
      Pacifastacus leniusculus.
AB  - To identify proteins associated with development of different hemocyte types in
      the freshwater crayfish Pacifastacus leniusculus, 2-DE followed by MS analysis
      was carried out with hematopoietic tissue (Hpt) cells, semigranular cells (SGC)
      and granular cells (GC). Within the hemocyte lineages one two-domain Kazal
      proteinase inhibitor (KPI) was found to be specific for SGC, while a superoxide
      dismutase (SOD) was specific for GC at protein as well as at mRNA level. The
      proliferation cell nuclear antigen (PCNA) was detected at the mRNA level in Hpt
      cells only. We also provide evidence that SGC and GC most likely differentiate to
      maturation as separate lineages. We found that after laminarin or
      lipopolysaccharide (LPS) injection into crayfish, the transcript levels of PCNA
      and SOD increased in the Hpt cells, whereas the KPI transcript never was present
      in Hpt regardless of any challenge. RNA interference of PCNA in the Hpt cells led
      to that most of the cells did not spread or attach to the tissue culture dish.
      These results suggest that PCNA, KPI and SOD can be used as markers for Hpt
      cells, SGC and GC, respectively, and in conjunction with these results, a model
      is proposed how the Hpt responds to a microbial challenge by proliferation and
      release of Hpt cells.

PMID- 18814329
TI  - Subproteomic tools to increase genome annotation complexity.
AB  - Comprehensive and precise annotations of short protein-coding genes are always a
      challenging task. Here we propose a new design to facilitate the characterization
      of previously overlooked short protein-coding genes by integrating a shotgun
      proteomics method and oligonucleotide array analysis. Using Shigella flexneri as
      a model, we validate 163 annotated ORFs and 51 hypothetical or putative
      transcripts at the protein level, and discover four novel short ORFs. This
      strategy will contribute significantly to comprehensive and accurate genome-wide
      annotation, and to our understanding of prokaryotic genome structure.

PMID- 18814330
TI  - Simplified validation of borderline hits of database searches.
AB  - Along with unequivocal hits produced by matching multiple MS/MS spectra to
      database sequences, LC-MS/MS analysis often yields a large number of hits of
      borderline statistical confidence. To simplify their validation, we propose to
      use rapid de novo interpretation of all acquired MS/MS spectra and, with the help
      of a simple software tool, display the candidate sequences together with each
      database search hit. We demonstrate that comparing hit database sequences and
      independent de novo interpretations of the same MS/MS spectra assists in rapid
      examination of ambiguous matches.

PMID- 18814331
TI  - Proteomic analysis of alterations in the secretome of Arabidopsis thaliana
      suspension cells subjected to nutritional phosphate deficiency.
AB  - A proteomic approach was applied to compare the secretome (culture filtrate
      proteome) of phosphate-sufficient (+Pi) and Pi-deficient (-Pi) Arabidopsis
      thaliana suspension cell cultures. Secretomes harvested from the +Pi and -Pi
      cells yielded dissimilar 2-DE maps. PMF via MALDI-TOF MS resulted in the
      identification of 50 protein spots representing 37 discrete proteins having
      unique gene identities. A total of 24 Pi-starvation responsive proteins were
      identified, with 18 of these being up-regulated and six down-regulated. Secreted
      proteins up-regulated by the -Pi cells included a ribonuclease involved in Pi
      scavenging from extracellular nucleic acids, as well as enzymes of cell wall
      modification, proteolysis, pathogen responses, and ROS metabolism. Enzyme
      activity assays and immunoblotting demonstrated that a pair of purple acid
      phosphatase isoforms having subunit M(r)s of 65 and 55 kDa was also secreted by
      the -Pi cells. Semiquantitative RT-PCR was used to assess the relationship
      between mRNA levels and relative amounts of selected secretome proteins. The
      results indicate that transcriptional control is but one of many factors
      contributing to Arabidopsis Pi starvation responses, and highlight the importance
      of parallel biochemical/proteomic studies of -Pi plants.

PMID- 18814332
TI  - Cerebrospinal fluid-optimized two-dimensional difference gel electrophoresis (2-D
      DIGE) facilitates the differential diagnosis of Creutzfeldt-Jakob disease.
AB  - So far only the detection of 14-3-3 proteins in cerebrospinal fluid (CSF) is
      included in the diagnostic criteria for sporadic Creutzfeldt-Jakob disease
      (sCJD). However, this assay cannot be used for screening because of the high rate
      of false positive results in sCJD, and often negative results in variant CJD. To
      facilitate the differential diagnosis of CJD, we applied 2-D differential gel
      electrophoresis (2-D DIGE) as a quantitative proteomic screening system for CSF
      proteins. We compared 36 patients suffering from sCJD with 30 patients suffering
      from other neurodegenerative diseases. Sample preparation was optimized in
      consideration of the fact that CSF is composed of blood- and brain-derived
      proteins, and an improved 2-D DIGE protocol was established. Using this method in
      combination with protein identification by MALDI-TOF-MS, several known surrogate
      markers of sCJD like 14-3-3 protein, neuron-specific enolase, and lactate
      dehydrogenase were readily identified. Moreover, a not yet identified protein
      with an approximate molecular mass of 85 kDa was found as marker for sCJD with
      high diagnostic specificity and sensitivity. We conclude that our proteomic
      approach is useful to differentiate CJD from other neurodegenerative diseases and
      expect that CSF-optimized 2-D DIGE will find broad application in the search for
      other brain derived proteins in CSF.

PMID- 18814333
TI  - Proteomics Data Collection - 3rd ProDaC workshop April 22nd 2008, Toledo, Spain.
AB  - The "Coordination Action" ProDaC (Proteomics Data Collection) - funded by the EU
      within the 6th framework programme - was created to support the dissemination,
      utilization and publication of proteomics data. Within this international
      consortium, standards are developed and maintained to support extensive data
      collection by the proteomics community. An important part of ProDaC are workshops
      organized on a regular basis (two per year) to allow discussions and
      communication between the ProDaC partners and to report on the progress of the
      project. The kick-off meeting took place in October 2006 in Long Beach, CA, USA.
      The 1st ProDaC workshop was held in Lyon, France (April 2007) and the 2nd in
      Seoul, Korea in October 2007. ProDaC organized the 3rd ProDaC workshop at the
      Beatriz Hotel, Toledo, on 22nd April, 2008, directly before the HUPO - PSI spring
      meeting (Human Proteome Organisation - Proteomics Standards Initiative). The work
      package coordinators presented talks about the progress achieved during the past
      six months. Additionally four external speakers presented their work on data
      conversion and data repositories. The concluding discussion session was chaired
      by the Journal's representative.

PMID- 18814334
TI  - 1st Irish proteomics workshop April 17th 2008, University College Dublin, Conway
      Institute, Dublin, Ireland.
AB  - The workshop assembled an excellent collection of speakers from across Ireland
      and beyond who presented many interesting and diverse topical issues. Various
      proteomic applications were discussed throughout the day ranging from 2-DE and 2
      D DIGE, to GeLC-MS/MS, high density Protein and Antibody Arrays, with a
      particular focus on the importance of quantitative mass spectrometry in
      proteomics.

PMID- 18814335
TI  - Annual spring meeting of the Proteomics Standards Initiative 23-25 April 2008,
      Toledo, Spain.
AB  - The role of the Human Proteome Organisation Proteomics Standards Initiative (HUPO
      PSI) is to produce and release community-accepted reporting requirements,
      interchange formats and controlled vocabularies for mass spectrometry proteomics
      and related technologies such as gel electrophoresis, column chromatography and
      molecular interactions. A number of significant advances were made at this
      workshop, with the new MS standard, mzML, being finalised prior to release on
      1(st) June 2008 and analysisXML, which will allow protein and peptide
      identifications and post-translational modifications to be captured, being
      prepared to enter the review process this summer. The accompanying controlled
      vocabularies are continuing to evolve and a number of standards papers are now
      being finalised prior to publication.

PMID- 18814336
TI  - Physiology of Streptococcus thermophilus during the late stage of milk
      fermentation with special regard to sulfur amino-acid metabolism.
AB  - Streptococcus thermophilus is a thermophilic lactic acid bacterium widely used as
      starter in the manufacture of dairy products in particular in yoghurt manufacture
      in combination with Lactobacillus delbrueckii ssp. bulgaricus. However, in spite
      of its massive use, the physiological state of S. thermophilus in milk has hardly
      been investigated. We established the first map of the cytosolic proteome of S.
      thermophilus LMG18311 grown in milk. It comprises 203 identified proteins
      corresponding to 32% of theoretical proteome. In addition, using proteomic and
      transcriptomic approaches, we analyzed the physiology of LMG18311 during its late
      stage of growth in milk (between 2h30 and 5h30). It revealed the up-regulation of
      (i) peptides and AA transporters and of specific AA biosynthetic pathways notably
      for sulfur AA and (ii) genes and proteins involved in the metabolism of various
      sugars. These two effects were also observed in LMG18311 grown in milk in
      coculture with L. bulgaricus although the effect on sugar metabolism was less
      pronounced. It suggests that the stimulatory effect of Lactobacillus on the
      Streptococcus growth is more complex than AA or peptides supply.

PMID- 18814337
TI  - Heat induced changes in protein expression profiles of Norway spruce (Picea
      abies) ecotypes from different elevations.
AB  - Although tree species typically exhibit low genetic differentiation between
      populations, ecotypes adapted to different environmental conditions can vary in
      their capacity to withstand and recover from environmental stresses like heat
      stress. Two month old seedlings of a Picea abies ecotype adapted to high
      elevation showed lower level of thermotolerance and higher level of tolerance to
      oxidative stress relative to a low elevation ecotype. Protein expression patterns
      following exposure to severe heat stress of the two ecotypes were compared by
      means of 2-DE. Several proteins exhibiting ecotype and tissue specific expression
      were identified by MS/MS. Among them, small heat shock proteins of the HSP 20
      family and proteins involved in protection from oxidative stress displayed
      qualitative and quantitative differences in expression between the ecotypes
      correlated with the observed phenotypic differences. On the basis of these
      results, it can be speculated that the observed interpopulation polymorphism of
      protein regulation in response to heat stress could underlie their different
      capacities to withstand and recover from heat stress. These local adaptations are
      potentially relevant for the species adaptation to the conditions predicted by
      the current models for climate change.

PMID- 18814338
TI  - Parameatal urethral cyst.
AB  - Cyst formation in the parameatal area of the urethra is an uncommon entity. It
      was first reported in two male cases as recently as 1956 by Thompson and Lantin.
      Further reports have been rare. Herein, we report a case of a 21 year-old male
      having a spherical, cystic swelling 1 cm in size at the external urethral meatus.
      The diagnosis of parameatal urethral cyst was made and the cyst was excised.
      Histopathological examination revealed a monolocular cyst lined with transitional
      cells. The postoperative period was uneventful.

PMID- 18814339
TI  - In-vitro activities of current antimicrobial agents against isolates of pyoderma.

PMID- 18814341
TI  - Proceedings of the annual meeting of the Society for Veterinary Epidemiology and
      Preventative Medicine (SVEPM). March 28-30, 2007. Helsinki, Finland.

PMID- 18814340
TI  - Hemorrhagic blisters in the mouth.

PMID- 18814342
TI  - Efficient differentiation of hESCs into endothelial cells in vitro is secured by
      epigenetic changes.
AB  - Human embryonic stem cells (hESCs) are to be considered as a valuable source for
      regenerative medicine because of their capacity to differentiate into all cell
      types. We have developed an efficient culture system to differentiate hECSs into
      endothelial cells without the formation of embryoid bodies Establishing
      appropriate culture conditions with a cocktail of growth factors allowed us to
      differentiate hESCs directly to endothelial primary culture with about 50%
      efficiency. CD31 immunomagnetic cell sorting was used to purify derived
      endothelium from the primary culture of hESCs. Isolated endothelial cells
      expressed immunological markers (vWF, CD105), specific genes (VE-cadherin, KDR,
      GATA-2, GATA-3, eNOS), and formed cord-like structures on collagen matrix and in
      Matrigel assay. During differentiation to endothelial lineage promoter regions of
      the genes involved in specific cell fate determination and homeostasis (GATA-2,
      3, and eNOS) underwent intensive hypomethylation which correlated with the gene
      expression. Overall our data demonstrate that direct differentiation of hESCs
      leads to endothelial cells that acquire epigenetic patterning similar to the
      functional endothelial cells of the organism.

PMID- 18814343
TI  - Proceedings of the European Workshop on Individual Monitoring of Ionising
      Radiation (IM2005). Vienna, Austria. April 11-15, 2005.

PMID- 18814344
TI  - Queering Norway. Special collection dedicated to Professor Jim Steakley for his
      contribution to gay, lesbian and queer scholarship in Europe and the USA.

PMID- 18814345
TI  - [Muscular hypotonia, developmental retardation, speech delay and mildly
      dysmorphic features: 22q13 deletion syndrome (Phelan-McDermid Syndrome) as an
      important differential diagnosis].
AB  - BACKGROUND: Clarifying the cause of global developmental and speech delay is of
      considerable significance in pediatrics. We present the clinical phenotype of the
      22q13 deletion syndrome - also known as Phelan-McDermid syndrome - and show the
      diagnostic options. PATIENT: We report on a female patient with muscular
      hypotonia, tall stature, minor facial dysmorphism, retarded motor and mental
      development, and severe speech delay. METHOD: Chromosomal analysis was performed
      first on peripheral lymphocytes on GTG-banded chromosomes. Fluorescence in situ
      hybridization (FISH) analysis was carried out using the dual-color LSI
      DiGeorge/VCFS Region Probe (TUPLE1, N25) (Vysis/Abbott) and the subtelomeric
      probe tel 22q13.3 (Tel Vysion 22q). RESULTS: The analysis of metaphase
      chromosomes at 450 band resolution showed a normal female karyotype 46,XX. FISH
      analysis revealed a 22q13 deletion. CONCLUSION: Muscular hypotonia and
      developmental delay are non-specific findings observed in many genetic syndromes.
      In association with severe speech delay and normal or advanced growth
      pediatricians should consider 22q13 deletion syndrome as a potential cause and
      initiate a genetic examination.

PMID- 18814346
TI  - Proceedings of the First Symposium on Cervical Cancer: challenging cervical
      cancer. Madrid, Spain. February 21-22, 2008.

PMID- 18814347
TI  - Myocardial metabolism-therapeutic aspects. Proceedings of the Fifth Annual
      Conference of the Society for Heart and Vascular Metabolism. June 18-20, 2007.
      Maastricht, The Netherlands.

PMID- 18814349
TI  - Proceedings of the X European Federation of Organizations for Medical Physics
      (EFOMP) Congress-First European Conference on Medical Physics. Il Ciocco, Italy.
      September 20-22, 2007.

PMID- 18814348
TI  - Proceedings of the 2007 Annual Meeting of the Society for the Study of Ingestive
      Behavior. June 24-28, 2007. Steamboat Springs, Colorado, USA.

PMID- 18814350
TI  - Proceedings of ExTech 2008-the 10th International Symposium on Advances in
      Extraction Techniques. January 28-30, 2008. Bruges, Belgium.

PMID- 18814351
TI  - Progress in dosimetry of neutrons and light nuclei. Proceedings of the Tenth
      International Symposium on Neutron Dosimetry. June 12-16, 2006. Uppsala, Sweden.

PMID- 18814352
TI  - Mechanisms and consequences of chromosomal translocation. Proceedings of a
      workshop. October 22-24, 2006. Warrenton, Virginia, USA.

PMID- 18814353
TI  - Mind on Canvas: anatomy, signs and neurosurgery in art.
AB  - Throughout the ages, art and neuroscience have had a delicate yet definite
      relationship with reciprocal influence. By virtue of their superior power of
      observation, artists have often preserved neurological signs through detailed
      brush strokes or meticulous carvings long before it is described in scientific
      literature. There has been an increasing tendency to use paintings and drawings
      as independent sources for investigation of scientific history. In neuroanatomy,
      these tools have helped reveal the complex interrelation between arts and
      neurosciences that on the surface often appear as highly polarized worlds. In
      this article we begin by giving a brief introduction to the general relationship
      between neuroscience and art as depicted in paintings and drawings, and describe
      the artistic tendencies of the early neuroanatomists. We aim to highlight the
      existence of neurosurgical themes within paintings and drawings from different
      eras.

PMID- 18814354
TI  - [Recommendations --antibiotic therapy strategy and prevention of bacterial
      resistance at health facilities].

PMID- 18814355
TI  - Mitochondria and cancer.
AB  - Mitochondria contained in cancer cells exhibit two major alterations. First, they
      are often relatively resistant to the induction of mitochondrial membrane
      permeabilization (MMP), which is the rate-limiting step of the intrinsic pathway
      of apoptosis. The mechanisms of MMP resistance have come under close scrutiny
      because apoptosis resistance constitutes one of the essential hallmarks of
      cancer. Second, cancer cell mitochondria often exhibit a reduced oxidative
      phosphorylation, meaning that ATP is generated through the conversion of glucose
      to pyruvate and excess pyruvate is then eliminated as the waste product lactate.
      This glycolytic mode of energy production is even observed in conditions of high
      oxygen tension and is hence called anaerobic glycolysis. Here, we discuss the
      molecular mechanisms accounting for inhibition of the mitochondrial apoptosis
      pathway in neoplasia and discuss possible mechanistic links between MMP
      resistance and anaerobic glycolysis.

PMID- 18814356
TI  - A view from the other side.

PMID- 18814357
TI  - Dr. Ness' E/M rule.

PMID- 18814358
TI  - Comparing anterior and posterior piggyback IOL power calculations in 2-optics and
      3-optics systems.

PMID- 18814359
TI  - Selected papers from the 14th European Carbohydrate Symposium, Lubeck, Germany,
      September 2007.

PMID- 18814360
TI  - HIV epidemic.  CDC issues revised number of new HIV infections.

PMID- 18814361
TI  - Report:  treatment, drug access for MSM still poor.

PMID- 18814362
TI  - Exposure.  Man's conviction for exposing teen to HIV upheld.

PMID- 18814363
TI  - HIV testing bill unanimously passes California Legislature.

PMID- 18814364
TI  - Asylum.  Deportation order upheld for 2 HIV-positive Colombian men.

PMID- 18814365
TI  - HIV-disclosure claim against prison guard dismissed.

PMID- 18814366
TI  - Financial.  Dismissal reversed for discharge of HIV-positive student's loans.

PMID- 18814367
TI  - Drug pricing.  AHF praises U.S. drugmaker for AIDS drug price freeze.

PMID- 18814368
TI  - Report from the XVII International HIV Drug Resistance Workshop.

PMID- 18814369
TI  - Guideline watch. Antiretroviral drug resistance testing--updated guidelines from
      the IAS-USA.

PMID- 18814370
TI  - Getting the most from available antiretroviral therapies.
AB  - Two decades after the approval of the first antiretroviral drugs, combination
      HAART has dramatically lowered the risk of illness and death for people with HIV.
      The year 2007 was another milestone, witnessing the approval of the first agents
      in two new anti-HIV drug classes--CCR5 antagonists and integrase inhibitors--that
      provide new options for treatment-experienced patients. Today, however, the anti
      HIV drug pipeline is relatively sparse, with no blockbusters in the foreseeable
      future. While the first HIV maturation inhibitor, bevirimat, continues to slowly
      make its way through clinical trials, another once-promising agent that works by
      a completely novel mechanism, Koronis Pharmaceuticals' KP-1461, was recently put
      on hold after laboratory tests indicated that it did not demonstrate the expected
      antiviral activity.

PMID- 18814371
TI  - When to start antiretroviral treatment: a changing equation.
AB  - The decision about when to start antiretroviral treatment is among the most
      vexing puzzles in the field of HIV management.HIV begins killing CD4 T-cells--key
      players in the body's immune response--from the time of initial infection, yet
      many HIV positive people go for years without experiencing clinical symptoms.
      Antiretroviral drugs effectively suppress viral replication and enable CD4 cell
      recovery, but also can lead to side effects that are at best bothersome and at
      worst debilitating or even fatal. While the optimal time to begin treatment for
      many diseases is as soon as possible after infection, in the case of HIV the
      decision involves balancing the benefits of preventing immune system decline--as
      well as other harmful effects of HIV infection that are only beginning to be
      understood--against the inconvenience, expense, and health risks associated with
      antiretroviral therapy.

PMID- 18814372
TI  - Trauma: frozen moments, frozen lives.

PMID- 18814373
TI  - Women and HIV. A new National Positive Women's Network.

PMID- 18814375
TI  - HIV prevention in Zambia: dropping the "C" from ABC.

PMID- 18814374
TI  - Confronting the 'evidence' in evidence-based HIV prevention: current scientific
      and political challenges.
AB  - Recent years have witnessed the increasing adoption of an evidence-based public
      health approach in HIV prevention science, yet this approach is limited by lack
      of consensus about what counts as "evidence." In 2007, the San Francisco AIDS
      Foundation (SFAF) launched an initiative to engage HIV/AIDS organizations,
      researchers, program implementers, policy makers, and funders in a robust
      discussion of what really constitutes "evidence" in evidence-based HIV
      prevention. The core of this initiative is a series of panel discussions about
      the gathering and interpreting of evidence for establishing efficacy and
      effectiveness in HIV prevention--evidence that is then used to inform decisions
      about which interventions to implement, fund, and scale up.

PMID- 18814377
TI  - Legal questions can arise when treating HIV-infected minors.

PMID- 18814376
TI  - D:A:D study shows that HIV therapy affects incidence rate of cardiac diseases.

PMID- 18814378
TI  - An in-depth look at the challenges of prescribing maraviroc.

PMID- 18814379
TI  - Starvation then binge-eating can cause obesity in the homeless.

PMID- 18814380
TI  - Personal reflections on  a 25-year career in HIV nursing.

PMID- 18814381
TI  - An approach for mapping the number and distribution of Salmonella contamination
      on the poultry carcass.
AB  - Mapping the number and distribution of Salmonella on poultry carcasses will help
      guide better design of processing procedures to reduce or eliminate this human
      pathogen from poultry. A selective plating media with multiple antibiotics
      (xylose-lysine agar medium [XL] containing N-(2-hydroxyethyl)piperazine-N'-(2
      ethanesulfonic acid) and the antibiotics chloramphenicol, ampicillin,
      tetracycline, and streptomycin [XLH-CATS]) and a multiple-antibiotic-resistant
      strain (ATCC 700408) of Salmonella Typhimurium definitive phage type 104 (DT104)
      were used to develop an enumeration method for mapping the number and
      distribution of Salmonella Typhimurium DT104 on the carcasses of young chickens
      in the Cornish game hen class. The enumeration method was based on the concept
      that the time to detection by drop plating on XLH-CATS during incubation of whole
      chicken parts in buffered peptone water would be inversely related to the initial
      log number (N0) of Salmonella Typhimurium DT104 on the chicken part. The sampling
      plan for mapping involved dividing the chicken into 12 parts, which ranged in
      average size from 36 to 80 g. To develop the enumeration method, whole parts were
      spot inoculated with 0 to 6 log Salmonella Typhimurium DT104, incubated in 300 ml
      of buffered peptone water, and detected on XLH-CATS by drop plating. An inverse
      relationship between detection time on XLH-CATS and N0 was found (r = -0.984).
      The standard curve was similar for the individual chicken parts and therefore, a
      single standard curve for all 12 chicken parts was developed. The final standard
      curve, which contained a 95% prediction interval for providing stochastic results
      for N0, had high goodness of fit (r2 = 0.968) and was N0 (log) = 7.78 +/- 0.61 -
      (0.995 x detention time). Ninety-five percent of N0 were within +/- 0.61 log of
      the standard curve. The enumeration method and sampling plan will be used in
      future studies to map changes in the number and distribution of Salmonella on
      carcasses of young chickens fed the DT104 strain used in standard curve
      development and subjected to different processing procedures.

PMID- 18814382
TI  - Differential magnification of rDNA gene types in bobbed mutants of Drosophila
      melanogaster.
AB  - In Drosophila melanogaster a partial loss of ribosomal genes leads to the bobbed
      phenotype. Magnification is a heritable increase in rDNA that may occur in males
      carrying a deleted X chromosome with a strong bobbed phenotype. The restriction
      patterns of X chromosome total rDNA, insertions and spacers from magnified bobbed
      strains were compared with those of the original bobbed mutations. It was found
      that magnification modifies restriction patterns and differentially affects gene
      types, increasing specific genes lacking insertions (INS-). Increases in copy
      number of genes with type I insertions are generally lower than the total number
      of INS- genes while type II insertion genes are not perceptibly increased. The
      recovery of homogeneous progeny from a single premagnified male indicates that
      the magnification event might take place and become stable very early in the germ
      line, arguing against magnification being due to extrachromosomal amplification.
      Additionally, some gene types increase 3.5-fold while others are eliminated,
      indicating that they could not result from a single unequal cross-over. These
      results are in good agreement with the existence of partial clustering of rDNA
      genes according to type, and suggest that magnification could result from local
      amplification of genes.

PMID- 18814384
TI  - Investigation of an outbreak of chikungunya in Malegaon Municipal areas of Nasik
      district, Maharashtra (India) and its control.

PMID- 18814383
TI  - Re: Diagnosis, screening, and treatment of root resorption in orthodontic
      practices in Greece and Sweden. Angle Orthodontist: Vol. 78, 248-253.

PMID- 18814385
TI  - Prescriptions for antipsychotic medications in schizophrenia.

PMID- 18814386
TI  - Preventing errors relating to commonly used anticoagulants.

PMID- 18814387
TI  - Trade-offs getting tougher: problems paying medical bills increase for U.S.
      families, 2003-2007.
AB  - About 57 million Americans were in families with problems paying medical bills in
      2007--an increase of 14 million people since 2003, according to a new national
      study by the Center for Studying Health System Change (HSC). Problems paying
      medical bills increased for both nonelderly insured and uninsured people.
      Although the rate of medical bill problems is much higher for uninsured people,
      most people with medical bill problems--42.5 million--had insurance coverage.
      About 2.2 million people with medical bill problems were in families that filed
      for bankruptcy as a result of their medical bills, and a much larger number
      reported other financial consequences, such as problems paying for other
      necessities and having to borrow money. The increase in medical bill problems-
      especially among insured people--is the main reason why more people reported
      unmet medical needs because of cost in 2007 than in 2003

PMID- 18814388
TI  - How do you know if it is really continuing education?

PMID- 18814389
TI  - Unmasking methamphetamine.

PMID- 18814390
TI  - Journaling: a strategy for developing reflective practitioners.

PMID- 18814391
TI  - Knowing who your partners are: terrorism-preparedness training for nurses.
AB  - Continuing education events addressing terrorism preparedness must be evaluated
      to measure their impact on knowledge acquisition and to assess changes in
      perceptions, attitudes, and beliefs. The purpose of this focus group study was to
      evaluate the effectiveness of a terrorism-preparedness training program. The
      majority of participants thought the training content was extensive, detailed,
      informative, and practical. Participants reported feeling increased confidence in
      their abilities to anticipate, recognize, and respond to a terrorist event, and
      said they made changes related to terrorism preparedness in their homes,
      workplaces, and communities. This evaluation was useful in identifying strengths
      and weaknesses of a statewide continuing education program and describing future
      training needs. Results may be useful to others who are planning terrorism
      preparedness training.

PMID- 18814392
TI  - Generational mentoring.
AB  - Healthcare organizations struggle with the best way to integrate new staff
      members, including novice and experienced nurses returning to practice, into the
      organization. One way of accomplishing this integration is mentoring. Mentoring
      is a process of guiding the development of another person. The methods used to
      mentor staff members can be influenced by the generation to which they belong.
      Each generation typically experiences different events that shape their
      expectations and responses. Consideration of the influence of these events can
      improve the effectiveness of the mentoring process.

PMID- 18814393
TI  - The financial impact of staff development.
AB  - Staff development educators need to refine their skills in measuring the impact
      of education activities on the organization's bottom line. Without this ability,
      when organizations are seeking to cut costs, the resources allocated to the
      education department are often reduced or eliminated. This article guides readers
      in identifying the organization's bottom line. Basic principles of budgeting, a
      template to calculate the actual costs of individual education activities, and
      methods to measure the impact of these activities on the organization's bottom
      line are included. A case study is used to demonstrate the process.

PMID- 18814394
TI  - An evaluation of preceptors' perceptions of educational preparation and
      organizational support for their role.
AB  - BACKGROUND: This longitudinal, descriptive study evaluated nurse preceptors'
      perceptions of a 2-day educational workshop and subsequent organizational support
      offered to prepare them for their roles as preceptors. METHODS: Thirty-six
      registered nurses who attended preceptor workshops and then acted as preceptors
      participated in focus groups or interviews 2 to 3 months and 6 to 9 months after
      their educational preparation to identify the usefulness of the preparation, the
      subsequent support by management, and the potential changes in their perceptions.
      RESULTS: Respondents identified intrinsic rewards and opportunities for growth
      for nurses who take on the preceptor role. However, adequate preparation and
      organizational support are essential to effectively perform their duties as
      clinicians and preceptors. CONCLUSION: Although a 2-day educational preparation
      program was perceived as adequate, the practice setting must be reorganized to
      provide greater support for preceptors. Preceptors should be supported by
      providing continuing education, effective scheduling, and adequate time for
      learning and feedback in the clinical environment.

PMID- 18814395
TI  - Cultural sensitivity education for nurses: a pilot study.
AB  - Health professionals need to be responsive to changing demographics, especially
      the growing Hispanic American population. This pilot project explored the effect
      that an education program about selected Hispanic health beliefs and practices
      had on nurses who provide care to this population. Seven white registered nurses
      employed at a small, rural health department completed a 10-item, researcher
      designed instrument, termed the Lee Cultural Sensitivity Tool: Hispanic Version,
      before and after an educational intervention. Findings showed that the
      intervention increased knowledge of selected Hispanic health beliefs and
      practices.

PMID- 18814396
TI  - Five year HIV plan still on course.

PMID- 18814397
TI  - HPV vaccination: taking the knowledge to the streets.

PMID- 18814398
TI  - The nation's sexual health--and how to improve it--is the subject of ongoing
      debate, and rightly so.

PMID- 18814399
TI  - Healthy, enjoyable and sustainable eating.

PMID- 18814400
TI  - Public health from the bottom up.

PMID- 18814401
TI  - Building bridges with young people.

PMID- 18814402
TI  - Making it real.

PMID- 18814403
TI  - Determinants of family size in a Gulf Arab state: a comparison between two areas.
AB  - AIMS: The rapid economic transition in the Gulf Arab countries has resulted in
      marked changes in fertility and marriage patterns and a decrease in the number of
      children per family. Yet little is known about the determinants of family size in
      urban and less urban areas. METHODS: A cross-sectional study was carried out on
      450 Kuwaiti women aged 20-60 years who attended health care centres in Al Asima
      and Al Jahra governorates. A semi-structured questionnaire was administered
      through face-to-face interview which included variables on socio-demographic
      characteristics, family size, actual and ideal spacing, marriage related
      variables, health conditions and utilization of health services. Both univariate
      and multivariate analyses were performed to identify the factors that affect
      family size. RESULTS: The socio-economic indicators were significantly better in
      Al Asima, the capital, than in Al Jahra, a less urbanized area. On average,
      family size for the total sample was 5.97 +/- 0.114 with a larger size (6.27 +/-
      0.242) in Al Jahra than in Al Asima (5.80 +/- 0.118) but without a significant
      difference. Al Jahra women reported a larger number of deliveries and past
      pregnancies but a lower usage of contraceptive measures. The total fertility rate
      was 3.65 in Al Asima, 3.84 in Al Jahra and 3.71 births per woman in the total
      population. Family size was inversely related to the educational level of women
      and their husbands. Currently employed women had a smaller family size (5.22 +/-
      0.119) than the unemployed (6.81 +/- 0.187); p < 0.0005. Health problems in the
      interviewee or her husband played a minor role in the decision to have more
      children. Families where the husband was the decision-maker on the number of
      children had a significantly larger family size (6.91 +/- 0.451) than families
      where the couple both participated in the decision (5.83 +/- 0.129; p = 0.032).
      The duration of marriage, ideal number of children, age of women at last
      delivery, number of rooms and the crowding index had significant positive effects
      on family size, whereas age at first delivery, duration between two consecutive
      pregnancies and history of past abortions were inversely related to family size
      in the stepwise multiple regression analysis. CONCLUSIONS: Although women in the
      less urbanized areas in the Gulf Arab populations are more disadvantaged with
      respect to socio-economic characteristics than women in the more urbanized areas,
      there were no significant differences in family size in these contrasting
      communities. The impact of socio-demographic characteristics on family size was
      minor compared to factors related to fertility and the husband's desire to have
      more children. Fertility and family planning policies should consider these
      issues in order to promote more effective programmes.

PMID- 18814404
TI  - Knowledge, beliefs and attitudes about HIV/AIDS-related issues, and the sources
      of knowledge among health care professionals in southern Nigeria.
AB  - The HIV/AIDS pandemic has become one of the most important public health problems
      in recent times and it is having a profound impact on the lives of infected
      people and their families. There is an acknowledged burden of HIV/AIDS in
      Nigeria. As the prevalence of HIV/AIDS infection rises, health care professionals
      worldwide can expect greater clinical exposure to infected patients. The care of
      people living with AIDS presents a significant challenge to the health care
      sector. This study seeks to explore the relationship between sources of HIV/AIDS
      information and knowledge, and the relationship between knowledge of HIV/AIDS and
      care for people with AIDS among health care providers in three different levels
      of health care institutions in the southern region of Nigeria. Health care
      workers from two states in southern Nigeria completed a questionnaire that was
      designed to assess knowledge, attitudes and practices about HIV/AIDS. The sample
      was composed of 277 (65%) females and 135 (31.7%) males. The results showed a
      fair level of knowledge among all health care professionals, with the highest
      level of knowledge among the doctors and the lowest among laboratory workers.
      There was a significant gender difference in the level of knowledge but the data
      suggested that knowledge did not differ by hospital settings. There were
      generally negative feelings and views about the care of HIV/AIDS patients among
      the professionals, these views being worst at the community health centers and
      best at the government hospital. The greatest source of information for the
      majority of professionals was health talks/seminars, and those respondents who
      got their information from school scored the highest on the items on general
      knowledge of HIV/AIDS incidence, cause, transmission, and clinical treatment.
      This has important implications for future interventions designed for health care
      professionals including doctors, nurses and laboratory workers.

PMID- 18814405
TI  - A call for mental health needs assessments in HIV positive children in Africa.
AB  - There is a worldwide pandemic of HIV infection. The WHO has compiled estimates of
      cases of HIV/AIDS for each country. In sub-Saharan Africa, HIV infection is
      causing decreased life expectancy. There is an overall increase in the number of
      orphans as a result of AIDS. Poverty, the lack of technologies and adequate
      resources are widening the gap between Africa and industrialized countries. In
      the instance of HIV positive children in Africa, we should aim to look into ways
      to identify and treat those with mental health issues or at risk for future
      mental health problems. This will help those affected to cope with the chronic
      illness associated with HIV infection, and to better comply with treatment that
      may lead to improved outcomes in terms of their quality of life.

PMID- 18814406
TI  - The prevalence of other sexually transmitted infections in confirmed HIV cases at
      a referral clinic in Jamaica.
AB  - Jamaica has the second highest number of acquired immunodeficiency syndrome
      (AIDS) cases and deaths in the Caribbean and a significant number of human
      immunodeficiency virus (HIV) infected individuals have a concomitant sexually
      transmitted infection (STI). The study determined the prevalence of non
      ulcerative and ulcerative STIs and their association with sexual risky behaviour
      in a sample of HIV seropositive men and women. This study was conducted at the
      Comprehensive Health Centre in Jamaica, a sexually transmitted infection referral
      centre. The sample comprised 138 men and 132 women age 15-49 years, of average
      29.5 years. The study was retrospective, from 2000 to 2002, and sample collection
      was randomized. The sexual behaviours of the subjects were assessed from the case
      records. In the 270 HIV diagnosed cases examined, the prevalence of STIs was
      51.1% in men and 48.9% in women, with 85.4% having one or more STIs with an
      average of four STIs per patient. There was a total occurrence of 744 STIs with
      non-gonococcal urethritis (19.4%), gonorrhoea (17.2%), candidiasis (13.4%),
      trichomonas (12.4%), genital ulcer (10.4%) and syphilis (7.3%) the most common in
      HIV infected men and women. The presence of STI was associated with continued
      practice of risky sexual behaviour. The age group most implicated was the 30-34
      year old, and 73.1% of the HIV infected patients had multiple sexual partners
      with only 16.4% reporting frequent condom use. The study demonstrates that there
      is a high prevalence of non-ulcerative and to a lesser extent ulcerative STIs in
      HIV infected patients in Jamaica. There are significant associations between STIs
      and continued high risk sexual practices in HIV infected men and women. The
      findings support the need for implementation of effective diagnosis and treatment
      strategies coupled with education about safe-sex practices in HIV prevention and
      STI control programmes.

PMID- 18814407
TI  - Targeted versus global approaches to the management of hypercholesterolaemia.
AB  - AIMS: The role of statins in secondary prevention of cardiovascular disease is
      well established. However, there is debate about the most effective approach to
      primary prevention. This study simulated the effects of directed versus global
      approaches for intervention on coronary heart disease (CHD) event rates. METHODS:
      A primary prevention population was generated by computer simulation derived from
      data from the National Health Survey for England. The efficacy of reductions in
      cholesterol, treatment to cardiovascular risk targets and effects of phytosterols
      or statins were assessed. RESULTS: A 0.5 mmol/L reduction in population total
      cholesterol would result in a 10.4% reduction in CHD events, while 1.0 mmol/L,
      1.5 mmol/L and 2.0 mmol/L reductions would achieve 21.0%, 30.6% and 41.9%
      reductions respectively. In statin-based cardiovascular risk targeted strategies,
      use of simvastatin 40 mg would result in 1.8% reduction by UK National Service
      Framework targets of 30%/decade CHD risk and 7.2% reduction in events for a
      20%/decade target assuming perfect adherence. Similarly, aggressive primary
      prevention with 40 mg atorvastatin would result in a 2.5% or 10% reduction in
      events. Universal use of 10 mg simvastatin following an over-the-counter approach
      would result in a 25% reduction in CHD events. In contrast, whole population
      consumption of sitostanol/sitosterol products would result in 11.8% reduction.
      CONCLUSION: Targeting and treating high-risk individuals may be beneficial for
      them and rewarding for medical practitioners. However, this approach has minimal
      effects on the population burden of atherosclerotic disease. This study suggests
      that universal therapy with phytosterols and/or wider availability of statins has
      the potential to dramatically decrease rates of CHD.

PMID- 18814408
TI  - Improved arthritic knee health in a pilot RCT of phytotherapy.
AB  - Although practitioner-prescribed 'western' herbal medicine (phytotherapy) is a
      popular complementary therapy in the UK, no clinical studies have been reported
      on patient-orientated outcomes. The objective of this pilot study was to
      investigate the effects of phytotherapy on symptoms of osteoarthritis of the
      knee. A previous study of Chinese herbal medicine for the treatment of irritable
      bowel syndrome, published in the Journal of the American Medical Association,
      acted as a model in the development of the protocol of this investigation. Twenty
      adults, previously diagnosed with osteoarthritis of the knee, were recruited from
      two Inner London GP practices into this randomized, double-blind, placebo
      controlled, pilot study carried out in a primary-care setting. All subjects were
      seen in consultation three times by a herbal practitioner who was blinded to the
      randomization coding. Each subject was prescribed treatment and given lifestyle
      advice according to usual practice: continuation of conventional medication where
      applicable, healthy-eating advice and nutrient supplementation. Individualized
      herbal medicine was prescribed for each patient, but only dispensed for those
      randomized to active treatment-- the remainder were supplied with a placebo. At
      baseline and outcome (after ten weeks of treatment), subjects completed a food
      frequency questionnaire and the Western Ontario and McMaster Universities
      Osteoarthritis Index (WOMAC) knee health and Measure Yourself Outcome Profile
      (MYMOP) wellbeing questionnaires. Subjects completing the study per protocol (n =
      14) reported an increased intake of wholegrain foods (p = 0.045) and oily fish (p
      = 0.039) compared to baseline, but no increase in fruit and vegetables and dairy
      products intakes. There was no difference in the primary outcome measure of knee
      health assessed as the difference in the mean response (baseline-week 10) in
      WOMAC score between the two treatment groups. However, there was, compared with
      baseline, improvement in the active group (n = 9) for the mean WOMAC stiffness
      sub-score at week 5 (p = 0.035) and week 10 (p = 0.060) but not in the placebo
      group (n = 5). Furthermore, for the active, but not the placebo group, the mean
      WOMAC total and sub-scores all showed clinically significant improvement (> or =
      20%) in knee symptoms at weeks 5 and 10 compared with baseline. Moreover, the
      mean MYMOP symptom 2 sub-score, mostly relating to osteoarthritis (OA), showed
      significant improvement at week 5 (p = 0.02) and week 10 (p = 0.008) compared
      with baseline for the active, but not for the placebo group. This pilot study
      showed that herbal medicine prescribed for the individual by a herbal
      practitioner resulted in improvement of symptoms of OA of the knee.

PMID- 18814409
TI  - Osteoporotic Caucasian and South Asian women: a qualitative study of general
      practitioners' support.
AB  - Health professionals face two complicated but contradictory epidemics: obesity
      and osteoporosis (OP). While obesity is obvious, OP progresses silently affecting
      one in two UK women. Both South Asian and Caucasian women are at OP risk. This
      study compared experiences of osteoporotic Caucasian and South Asian women in a
      purposive sample of 21 volunteers from south east England, aged 43 to 82 years.
      The women had been diagnosed for eight months to 40 years. Long disease duration
      was marked by complacent OP dialogue, although OP was objectionable and marked a
      loss of quality of life. Inductive content analysis of transcripts showed that
      'uncertainty'--about one another and about what constituted helpful self-care-
      affected both GPs and patients. Instead, support groups and the media supported
      learning about OP care. Beyond providing drug prescriptions, women reported
      desiring, but rarely feeling, that GPs fully supported their preferences for self
      care. Self-care often included specialist exercise classes. Some younger women
      led their GPs to better understand the range of self-care options. GPs were seen
      as being unsure about how and when to discuss physical activity (PA). In
      conclusion, women with OP in this sample are sensitive to their GP's hesitance
      about offering detailed PA recommendations. Regardless of ethnicity, younger
      women undertook PA based on personal initiative. Positive PA experiences
      stimulated an interest in discussing PA with GPs, and these dialogues broke the
      silence surrounding OP care. By providing important information regarding the OP
      patient experience, the findings highlight the unmet desire of OP sufferers for
      better and closer attention from GPs.

PMID- 18814410
TI  - Beyond claims processing.

PMID- 18814411
TI  - Benefits of automating and integrating your eligibility processes.

PMID- 18814412
TI  - Four more tips to reduce orthopedic implant costs and keep physicians happy.

PMID- 18814413
TI  - Sensitivity influencing decisions for surgical gloves.

PMID- 18814414
TI  - Go through your GPO's contracts for lower prices.

PMID- 18814415
TI  - Oil costs can cause your expenses to slip out of control.

PMID- 18814416
TI  - Researchers buoyed by new discoveries.

PMID- 18814418
TI  - Top 40 assisted living chains. 2007. Sunrise continues to hold top spot.

PMID- 18814417
TI  - Top 50 nursing facility chains. 2007. Steady growth.

PMID- 18814419
TI  - SNF reaps rewards of EMR adoption.

PMID- 18814420
TI  - HIT bill stalled over privacy concerns.

PMID- 18814421
TI  - Reinventing the wheelchair.

PMID- 18814422
TI  - Articles examining several exciting innovations in health care settings in
      Canada.

PMID- 18814423
TI  - Developing an innovative care delivery model: interprofessional practice teams.
AB  - An interprofessional project team at the University Health Network (UHN)
      completed a project to develop an Interprofessional Patient-Centred Practice
      (IPCP) Framework, explore enablers and barriers to collaborative practice and
      recommend a model of care delivery and interprofessional practice. The following
      recommendations were made: adopt proposed IPCP Framework as the basis for
      developing interprofessional teams, implement an IPCP tool kit as a resource,
      develop evidence-based interventions across health care teams, and educate health
      professionals on IPCP.

PMID- 18814424
TI  - From pilot project to annual success: creating an evidence-based leadership
      program for medical directors in long-term care.
AB  - Engaging physicians in health care administration is critical. Within Canada,
      physician leadership programs have not been designed to meet the needs of medical
      directors in Long-Term Care (LTC). This article explains how a pilot program for
      medical directors in LTC was created to develop their leadership skills, and how
      it has now become an annual event. The program must evolve to enable medical
      directors to participate in system change and innovation within LTC.

PMID- 18814425
TI  - Workplace wellness programs in Canada: an exploration of key issues.
AB  - Faced with the reality of rising health costs, Canadian employers are thinking
      beyond traditional notions of responsibility for employee health and have begun
      to embrace Workplace Wellness Programs (WWPs). This article investigates the
      critical issues of WWPs in the Canadian context from the perspective of key
      stakeholders. Using a combination of literature and key informant interviews,
      seven key themes are presented along with recommendations for wider
      implementation of WWPs in Canada.

PMID- 18814426
TI  - A review of evidence on the reliability and validity of Minimum Data Set data.
AB  - This paper reviews the reliability and validity of the Minimum Data Set (MDS)
      assessment, which is being used increasingly in Canadian nursing homes and
      continuing care facilities. The central issues that surround the development and
      implementation of a standardized assessment such as the MDS are presented,
      including implications for health care managers in how to approach data quality
      concerns. With other sectors such as home care and inpatient psychiatry using MDS
      for national reporting, these issues have importance in and beyond residential
      care management.

PMID- 18814427
TI  - Conversation with Ray J. Racette, CHE, President and CEO, CCHSE.

PMID- 18814428
TI  - Your ethics questions answered: sharing information with a job applicant's
      employer.

PMID- 18814429
TI  - Antagonistic effect of low deprenyl dose on the preimplantation embryo
      development in rat.
AB  - To investigate the role of potent MAO-B inhibitor deprenyl in fertilized females,
      we have evaluated the effect of chronic treatment with deprenyl at a low dosage
      on preimplantation embryo development in Wistar rats. We have found that the
      number of isolated embryos per rat did not differ between experimental and
      control groups. But morphological analysis of embryos isolated from deprenyl
      treated animals had revealed improved rates in the distribution pattern compared
      with controls. On the other hand, harmful impact of deprenyl administration on
      the mean cell number in blastocysts and on their cell proliferation has been
      recorded. To our knowledge this is the first paper describing antagonistic effect
      of deprenyl administration on the preimplantation embryo development in mammals.
      Potential mechanisms mediating biphasic deprenyl-induced impact on embryonic
      development are proposed (Tab. 3, Ref. 17). Full Text (Free, PDF) www.bmj.sk.

PMID- 18814430
TI  - Low density lipoprotein subclass distribution in children with diabetes mellitus.
AB  - BACKGROUND: The role of small dense low-density lipoprotein (sLDL) subclasses in
      atherosclerosis has been demonstrated in many studies. Among other metabolic
      changes, the alteration in LDL lipoprotein subclass distribution and size has
      been proved in diabetic adults. Because there is not enough literature data
      presenting LDL subclass distribution in childhood, the aim of this study was to
      examine LDL subclass profile in diabetic children compared with healthy control.
      MATERIAL AND METHODS: Plasma LDL subclasses in 30 children with type I diabetes
      mellitus and 100 healthy children aged 9-18 years were analyzed using non
      denaturing polyacrilamide gradient (3-31%) gel electrophoresis. Conventional
      plasma lipid and apoprotein parameters which are thought to affect LDL size were
      determined as well. RESULTS: Analysis of LDL phenotype has shown that a great
      percentage of healthy children (89%) yield bigger LDL1 with LDL2 subclasses being
      dominant (phenotype A), whereas 11 % of the children belong to phenotype B
      characterized by the presence of small, atherogenic LDL3 and LDL4 subclasses. In
      diabetic children despite no significant differences in their plasma lipid
      profile when compared with healthy control, the frequency of LDL phenotype B was
      increased (86.7 %), and the mean LDL diameter was smaller (p < 0.0001). LDL size
      was inversely correlated with plasma levels of triglycerides, and positively
      correlated with plasma HDL cholesterol and BMI. CONCLUSION: Although plasma
      levels for lipid and apoprotein were within the normal range, the increased
      frequency of LDL phenotype B confirms a grater risk of atherosclerosis
      development in children with diabetes mellitus. LDL size measurement may
      potentially help to assess cardiovascular risk and adapt the treatment goals
      thereafter (Tab. 3, Ref. 38). Full Text (Free, PDF) www.bmj.sk.

PMID- 18814431
TI  - Biochemical evaluation of the antiplatelet effect of aspirin in patients at
      different levels of cardiovascular risk.
AB  - BACKGROUND: The phenomenon called aspirin resistance is being intensively
      discussed. METHODS: To evaluate the biochemical aspirin response, the method of
      urinary 11-dehydro TXB2 levels measurement was used. Quantitative detection of
      TXB2 in urine was determined by competitive enzyme immunoassay, using human
      Thromboxane B2 ELISA-kit. We investigated the urine samples from 69 patients.
      RESULTS: The mean urinary levels of 11-dehydro TXB2 were significantly lower in
      patients in the primary and secondary types of aspirin prevention comparing with
      the control group of patients not taking aspirin. The difference in thromboxane
      concentrations between the two groups of patients taking aspirin did not reach
      statistical significance. Our results did not show significant differences in the
      biochemically measured aspirin response when comparing diabetics with non
      diabetics. Similarly, the observed tendency to higher thromboxane levels in women
      did not show to be significantly different from men. CONCLUSION: Our pilot study
      did not show any significant differences among patients at different
      cardiovascular risk. Since there is currently no standard laboratory method to
      detect aspirin non-responders available, the term aspirin resistance remains
      controversial and requires further research. Every effort should be done to
      improve patients' compliance and to prevent clinically relevant interactions of
      aspirin with ibuprofen. The elimination of these two factors as was the case in
      our study may provide better efficacy of the antithrombotic prevention by aspirin
      (Fig. 2, Tab. 4, Ref. 19). Full Text (Free, PDF) www.bmj.sk.

PMID- 18814432
TI  - The effectiveness for prevention of tuberculosis in patients with inflammatory
      rheumatic diseases treated with TNF inhibitors.
AB  - BACKGROUND: New biologic therapies blocking TNF undoubtly constitute a
      considerable advancement in the management mentioned diseases, but are also
      associated with higher risk of activation of tuberculosis. METHODS: An assessment
      of tuberculosis activation rate in the group of patients with rheumatoid
      arthritis, juvenile idiopatic arthritis, ankylosing spondylitis and psoriatic
      arthritis threated by anti-TNF inhibitors since January 1st 2001 to June 30th
      2007 in Slovakia and went in for special anti-tuberculosis screening before start
      of therapy. RESULTS: A total 537 rheumatic patients received the anti-TNF
      therapy. There were 346 rheumatoid arthritis patients, 68 juvenile idiopatic
      arthritis patients, 71 patients suffered from ankylosing spondylitis and 52 from
      psoriatic arthritis. Duration of anti-TNF therapy was 843 of patient-years.
      Infliximab took 203 patients with duration of therapy 348 patient-years,
      etanercept 201 patients with duration of therapy 331 patient-years and adalimumab
      133 patients with duration of therapy 164 patient-years. The activation of
      tuberculosis reached the incidence 0.37% (2 cases for 537 patients) representing
      0.237 cases for 100 patient-years. Both patients had extrapulmonary forms of
      tuberculosis which was in one patient disseminated, but they fully recovered
      after the anti-TNF drugs were stopped and chemotherapy was completed. CONCLUSION:
      Our results demonstrate a low incidence of tuberculosis activation during anti
      TNF treatment in patients with inflammatory rheumatic diseases in the Slovak
      Republic and confirm the high effectiveness ours specified complex screening
      measures (Tab. 3, Ref. 13). Full Text (Free, PDF) www.bmj.sk.

PMID- 18814433
TI  - Vertigo associated with Chiari I malformation and syringomyelia.
AB  - We report a rare case of a patient with late onset of Chiari I malformation with
      associated syringomyelia that was successfully treated with foramen magnum
      decompression. Our patient is presenting initially with vertigo and gradual
      weakening of the left-hand gross motor ability, gradual hypesthesia. Magnetic
      resonance imaging demonstrated a Chiari I malformation with syringomyelia.
      Posterior fossa decompression, C1 laminectomy and duroplasty were performed.
      After surgery, the vertigo completely resolved (Fig. 2, Ref. 13). Full Text
      (Free, PDF) www.bmj.sk.

PMID- 18814434
TI  - Nordic walking--is it suitable for patients with fractured vertebra?
AB  - This article brings the biomechanical analysis of sport--Nordic walking--for
      patients with osteoporotic fractured vertebrae and shows that it is suitable for
      them. Based on the biomechanical model of skeletal load we have developed a
      method of walking movement for patients, different from the method of walking
      movement for healthy people. And so came into being the "first sport" for
      patients with osteoporotic fractures. They can go for regular walks in easy
      terrains outdoors with friends and family, and so be liberated from social
      isolation. It requires only one-off financial costs of buying the poles and
      special footwear (Tab. 7, Fig. 3, Ref. 14). Full Text (Free, PDF) www.bmj.sk.

PMID- 18814435
TI  - Single parameter wrist ultrasonography as a first-line screening examination in
      suspected carpal tunnel syndrome patients.
AB  - Carpal tunnel syndrome (CTS) is the most common form of peripheral nerve
      entrapment. Electromyography with selected nerve conduction studies (NCS) is an
      accepted diagnostic tool in CTS patients. Ultrasonography presents a widely
      available and low cost investigation method and its position in CTS diagnostics
      needs further clarification with concrete recommendations for clinical practice.
      A prospective study of 37 patients with 74 wrists (59 wrists with suspected CTS)
      was done. Normative data were obtained from a control group of 25 healthy persons
      (50 wrists) age and sex matched. All persons underwent ultrasonographic
      examination (median nerve cross-sectional area at carpal tunnel entrance
      measurement--CSA) and median NCS studies (distal motor and sensory latency
      measurement--DML and DSL). RESULTS: CSA has a sensitivity of 93% (CI 84-97%) and
      specificity of 96% (CI 87-99%) in our patients group. Conventional first-line NCS
      studies results in our patients groupare as follows: DML sensitivity 58% (CI 45
      69%) and specificity 100% (CI 93-100%); DSL sensitivity 88% (CI 78-94%) and
      specificity 94% (CI 84-98%). CONCLUSION: We recommend the use of single-parameter
      wrist ultrasonography as a first-line screening laboratory method in suspected
      CTS diagnosis (Ref. 14). Full Text (Free, PDF) www.bmj.sk.

PMID- 18814436
TI  - The venous circle of Trolard.
AB  - A venous anastomotic network is occasionally found at the base of the brain,
      which closely resembles the vicinal arterial circle of Willis. When present, this
      venous polygon is composed of the anterior cerebral and communicating veins, the
      basal vein of Rosenthal and the posterior communicating and lateral mesencephalic
      veins. We propose that this anastomotic ring be termed the venous circle of
      Trolard. This venous circle might cause bleeding with such procedures as an
      endoscopic third ventriculostomy. We believe that information regarding this
      venous circle may be useful to neuroradiologists or neurosurgeons operating at
      the base of the brain (Fig. 1, Ref. 10). Full Text (Free, PDF) www.bmj.sk.

PMID- 18814437
TI  - Anomalous renal arteries and its clinical implications.
AB  - Often, the accessory renal arteries are observed near the hilum. Presence of
      anomalous accessory renal arteries may be associated with other underlying renal
      pathological conditions. We detected anomalous pattern of the renal arteries, in
      a 51 year old male cadaver, during routine undergraduate teaching program, in the
      department of Anatomy. The left renal artery originated at the level of the
      second lumbar vertebra and gave off two branches and each branch bifurcated into
      two branches which were destined to supply the suprarenal gland and the left
      kidney. However, the right renal artery displayed an early extra-renal division
      into two branches. The upper branch was found traversing to the upper pole,
      whereas the lower branch reached renal hilum by passing posterior to the renal
      pelvis. Anatomical description of this anomalous pattern of renal vasculature is
      presented in this case report, highlighting its clinical implications (Fig. 2,
      Ref. 10). Full Text (Free, PDF) www.bmj.sk.

PMID- 18814438
TI  - Central venous pressure--evaluation, interpretation, monitoring, clinical
      implications.
AB  - Physicians need to understand, evaluate and address hemodynamics in every patient
      and even more importantly in patients that are critically ill. Being able to
      determine and interpret central venous pressure is one of the most useful bedside
      evaluation skills, even in the 21st century (Fig. 3). Full Text (Free, PDF)
      www.bmj.sk.

PMID- 18814439
TI  - Marginalized populations and drug addiction research: realism, mistrust, and
      misconception.

PMID- 18814440
TI  - Continuing ethics review practices by Canadian research ethics boards.

PMID- 18814441
TI  - How independent are IRBs?

PMID- 18814442
TI  - Tree of heaven: Ailanthus altissima.

PMID- 18814443
TI  - Basic science for the practicing clinician.

PMID- 18814444
TI  - Noninvasive evaluation of airway inflammation in asthmatic patients who smoke:
      implications for application in clinical practice.
AB  - BACKGROUND: Despite the limited pathological data in asthmatic patients who
      smoke, it is thought that cigarette smoking may modify airway inflammation.
      OBJECTIVES: To summarize the major clinical studies that have used samples
      obtained by noninvasive techniques, such as blood, urine, exhaled breath
      condensate (EBC), fractional exhaled nitric oxide (FeNO), and induced sputum, for
      the evaluation of airway inflammation and the response to treatment in asthmatic
      patients who smoke and to evaluate which biomarkers have been adequately
      validated to be used in routine clinical practice. DATA SOURCES: In this review,
      we collected the available literature that addressed this topic. We searched the
      MEDLINE database using a combination of the following keywords: smoking or asthma
      or inflammation or mechanisms or exhaled nitric oxide or induced sputum or EBC.
      STUDY SELECTION: We selected the articles that most adequately addressed this
      topic for inclusion in this review. RESULTS: Smoking significantly influences
      FeNO and negatively affects its concentration, although FeNO can distinguish
      steroid-naive asthmatic smokers from nonasthmatic smokers. Sputum neutrophilia is
      the predominant finding in induced sputum in asthmatic patients who smoke but
      inflammatory mediators derived either from neutrophils or from a T(H)1 response
      can also be measured in the supernatants. EBC gives the opportunity to evaluate
      neutrophil-derived cytokines, airway acidification, and plausible protective
      mechanisms in smoking asthma. CONCLUSIONS: Despite the encouraging updated
      results, the introduction of noninvasive techniques in daily clinical practice
      requires the reworking of some methodologic pitfalls and the identification of a
      reliable biomarker that is reproducible, possesses normal values, and provides
      information for the underlying inflammatory process and the response to
      treatment.

PMID- 18814445
TI  - Asthma quality-of-care measures using administrative data: relationships to
      subsequent exacerbations in multiple databases.

PMID- 18814446
TI  - The burden of rhinitis in a managed care organization.
AB  - BACKGROUND: Rhinitis is a common health condition, but the extent of the burden
      in managed care organizations (MCOs) has not been well described. OBJECTIVE: To
      compare medical utilization in a large MCO of patients (1) with vs without
      rhinitis and (2) with allergic (AR) vs nonallergic (NAR) rhinitis. METHODS:
      Patients 4 years and older with 1 or more encounters with an International
      Classification of Diseases, Ninth Revision, code for rhinitis and patients
      treated for rhinitis but without a rhinitis encounter (rhinitis treatment-only
      group) were identified. Patients seen in allergy departments for rhinitis were
      categorized as having AR or NAR. RESULTS: Of 1,726,084 patients continuously
      enrolled for all 4 study years, 29% had 1 or more encounters for rhinitis (15%)
      or were treated for rhinitis (14%). Compared with patients without rhinitis,
      those with rhinitis encounters were significantly more likely to have encounters
      for asthma (odds ratio [OR], 2.7), acute sinusitis (OR, 4.4), chronic sinusitis
      (OR, 15.2), conjunctivitis (OR, 1.5), acute otitis media (OR, 1.9), chronic
      otitis media (OR, 4.3), sleep apnea (OR, 3.4), and fatigue (OR, 2.0). Results for
      rhinitis treatment-only patients (n = 242,565) were generally similar to those
      for rhinitis encounter patients. NAR was diagnosed in 21% of patients, who were
      significantly more likely than patients with AR to undergo sinus radiology and
      nasal surgery; to receive diagnoses of sinusitis, otitis media, sleep apnea, and
      fatigue; and to receive medications for nonrespiratory conditions (P < .001).
      CONCLUSIONS: Rhinitis was common in this large MCO. Patients with rhinitis,
      especially NAR, had significantly more respiratory and nonrespiratory comorbid
      conditions than did patients without rhinitis.

PMID- 18814447
TI  - Symptoms, spirometry, exhaled nitric oxide, and asthma exacerbations in clinical
      practice.
AB  - BACKGROUND: Patient symptoms, spirometry measurements, exacerbation rates, and
      exhaled nitric oxide (FE(NO)) levels have all been used to quantify asthma
      severity. OBJECTIVE: To determine the relationships among these disease
      surrogates in clinical practice. METHODS: Data were collected from 5 primary care
      asthma clinics on patient symptoms, reliever use, spirometry measurements,
      maintenance pharmacotherapy, disease severity (British Thoracic Society treatment
      step), and FE(NO) level. Exacerbation data (asthma-related unscheduled health
      care contact or rescue oral corticosteroid therapy) for the 12 months before and
      3 months after the clinic visit were then obtained. RESULTS: A total of 267 adult
      asthmatic patients (mean [SEM] age, 51.6 [1.1] years; forced expiratory volume in
      1 second, 86.3% [1.2%] of predicted) participated, and 157 exacerbations were
      captured. For the 12 months before the clinic visit, exacerbation rate was
      positively correlated with dose of inhaled corticosteroid (P < .001), treatment
      step (P < .001), reliever use (P = .002), and symptom score (P < .001) but was
      negatively correlated with FE(NO) level (P = .04); only symptom scores correlated
      with exacerbation rate in the 3 months after the visit. Levels of FE(NO) were
      significantly lower in frequently exacerbating patients receiving higher doses of
      maintenance inhaled corticosteroids compared with patients with mild disease who
      were corticosteroid naive (19.7 vs 40.4 ppb, P < .001). Measurement of FE(NO) was
      an insensitive method (sensitivity, 66.7%; specificity, 51.9% at a cutoff value
      of 20 ppb) for identifying patients who subsequently exacerbated. CONCLUSION:
      Levels of FE(NO) are paradoxically decreased in patients with more severe asthma
      and frequent exacerbations and may, therefore, be of limited utility in primary
      care.

PMID- 18814448
TI  - Racial disparities in asthma-related health outcomes in severe or difficult-to
      treat asthma.
AB  - BACKGROUND: The underlying reasons for racial disparities in asthma morbidity are
      not well understood. Multivariate epidemiologic studies evaluating the presence
      and extent of racial differences in a large cohort of adults with severe or
      difficult-to-treat asthma are lacking. OBJECTIVE: To analyze an extensive array
      of clinical and patient-reported outcomes, using multivariate analysis with a
      sequential approach, to explain racial differences in asthma-related outcomes in
      one of the largest cohorts of difficult-to-treat asthmatic patients. METHODS:
      Black and white patients (> or = 18-years-old at baseline) were included (n =
      2,128). Differences between the 2 racial groups were assessed using several
      outcome measures at month 12. Assessments were adjusted for confounding variables
      using a sequence of statistical models. RESULTS: Most patients were white
      (88.6%). Blacks were slightly younger, less educated, and more likely to live in
      urban areas than whites. Blacks were more likely to have severe asthma and to be
      treated with 3 or more long-term controllers. Poorer quality of life, more asthma
      control problems, and higher risk of emergency department visits were observed in
      blacks compared with whites; differences were not explained by adjustment for
      broad sets of confounding variables. Differences in asthma-related health
      outcomes remained statistically significant after adjusting for asthma severity.
      CONCLUSIONS: Asthma is a serious health problem in blacks and is not explained by
      differences in demographics, severity, or other health conditions.

PMID- 18814449
TI  - Barriers to adherence to asthma management guidelines among inner-city primary
      care providers.
AB  - BACKGROUND: Health care provider adherence to national asthma guidelines is
      critical in translating evidence-based recommendations into improved outcomes.
      Unfortunately, provider adherence to the National Heart, Lung, and Blood
      Institute (NHLBI) guidelines remains low. OBJECTIVE: To identify barriers to
      guideline adherence among primary care professionals providing care to inner
      city, minority patients with asthma. METHODS: We surveyed 202 providers from 4
      major general medicine practices in East Harlem in New York, New York. The study
      outcome was self-reported adherence to 5 NHLBI guideline components: inhaled
      corticosteroid (ICS) use, peak flow (PF) monitoring, action plan use, allergy
      testing, and influenza vaccination. Potential barriers included lack of agreement
      with guideline, lack of self-efficacy, lack of outcome expectancy, and external
      barriers. RESULTS: Most providers reported adhering to the NHLBI guidelines for
      ICS use (62%) and for influenza vaccinations (73%). Self-reported adherence was
      34% for PF monitoring, 9% for asthma action plan use, and 10% for allergy
      testing. Multivariate analyses showed that self-efficacy was associated with
      increased adherence to ICS use (odds ratio [OR], 2.8; P = .03), PF monitoring
      (OR, 2.3; P = .05), action plan use (OR, 4.9; P = .03), and influenza
      vaccinations (OR, 3.5; P = .05). Conversely, greater expected patient adherence
      was associated with increased adherence to PF monitoring (OR, 3.3; P = .03) and
      influenza vaccination (OR, 3.5; P = .01). Familiarity with specific guideline
      components and higher level of training were also predictors of adherence.
      CONCLUSIONS: Lack of outcome expectancy and poor provider self-efficacy prevent
      providers from adhering to national asthma guidelines. Efforts to improve
      provider adherence should address these specific barriers.

PMID- 18814450
TI  - Prenatal exposure to acetaminophen and respiratory symptoms in the first year of
      life.
AB  - BACKGROUND: Prevalence of asthma in developed countries increased between the
      1970s and the 1990s. One factor that might contribute to the trends in asthma is
      the increased use of acetaminophen vs aspirin in children and pregnant women.
      OBJECTIVE: To examine relationships between in utero exposure to acetaminophen
      and incidence of respiratory symptoms in the first year of life. METHODS: A total
      of 345 women were recruited in the first trimester of pregnancy and followed up
      with their children through the first year of life. Use of acetaminophen in
      pregnancy was determined by questionnaire and related to incidence of respiratory
      symptoms. RESULTS: Use of acetaminophen in middle to late but not early pregnancy
      was significantly related to wheezing (odd ratio, 1.8; 95% confidence interval,
      1.1-3.0) and to wheezing that disturbed sleep (odds ratio, 2.1; 95% confidence
      interval, 1.1-3.8) in the first year of life after control for potential
      confounders. CONCLUSION: This study suggests that use of acetaminophen in middle
      to late but not early pregnancy may be related to respiratory symptoms in the
      first year of life. Additional follow-up will examine relationships of maternal
      and early childhood use of acetaminophen with incidence of asthma at ages 3 to 5
      years, when asthma diagnosis is more firmly established.

PMID- 18814451
TI  - Studies of the mechanisms of bradykinin generation in hereditary angioedema
      plasma.
AB  - BACKGROUND: Factor XII-dependent bradykinin formation is thought to be
      responsible for the swelling associated with the various forms of C1 inhibitor
      deficiency, and complement activation is augmented during attacks of swelling.
      OBJECTIVES: To further elucidate the interactions of the kinin-forming cascade
      that lead to complement activation during attacks of swelling and to determine
      whether fibrinolysis is augmented as well. METHODS: We compared spontaneous and
      kaolin-induced activation of normal plasma with the plasma of patients with
      hereditary angioedema. RESULTS: Hereditary angioedema plasma demonstrated
      augmented factor XII activation, production of factor XIIf, prekallikrein
      activation, and high-molecular-weight kininogen cleavage, and, as a result,
      bradykinin formation was markedly increased. Baseline levels of C4a and plasmin
      alpha 2 antiplasmin complexes increased, and, on activation with kaolin, levels
      increased further. CONCLUSIONS: All parameters indicative of activation of the
      bradykinin-forming cascade are activated in hereditary angioedema plasma vs
      normal plasma. Production of factor XIIf, demonstrated for the first time in
      whole plasma, may be responsible for C1 activation based on C4a production. The
      factor XII-dependent fibrinolytic cascade is also activated.

PMID- 18814452
TI  - Efficacy comparison of levocetirizine vs montelukast in ragweed sensitized
      patients.
AB  - BACKGROUND: To date, no adequate data are available on direct comparison of the
      efficacy of levocetirizine, a recently approved histamine1-antihistamine, with
      that of a leukotriene antagonist in the treatment of seasonal allergic rhinitis
      (SAR) symptoms. OBJECTIVE: To compare the efficacy of therapeutic doses of 5 mg
      of levocetirizine and 10 mg of montelukast in ragweed sensitized patients.
      METHODS: A randomized, double-blind, placebo-controlled, parallel-group study was
      conducted between July and October 2006. Symptomatic patients with SAR were
      exposed to ragweed pollen under controlled conditions in an environmental
      exposure chamber for 4 to 5 hours after treatment with 5 mg of levocetirizine, 10
      mg of montelukast, or matched placebo on 2 consecutive days. The mean change from
      baseline in pollen-induced rhinitis symptoms, expressed as a major symptoms
      complex (MSC) score (sum of scores for rhinorrhea, itchy nose, sniffles, nose
      blows, sneezes, and watery eyes), in period 1 (first 5 hours after first drug
      intake) was the primary efficacy outcome. RESULTS: A total of 611 patients were
      screened, of whom 403 were randomized to receive treatment (102 placebo, 152
      levocetirizine, and 149 montelukast). The MSC score in period 1 was progressively
      decreased to a significantly greater extent in the levocetirizine group compared
      with the montelukast and placebo groups (adjusted mean differences, -2.18 [95%
      confidence interval, -3.35 to -1.01; P < .001] and -2.22 [95% confidence
      interval, -3.51 to -0.92; P < .001] for levocetirizine vs montelukast and vs
      placebo, respectively). The effect of 10 mg of montelukast was not significantly
      different compared with placebo. Levocetirizine also achieved a significantly
      faster onset of action within 2.5 hours of administration. Both products were
      well tolerated. CONCLUSIONS: This study in an environmental exposure chamber
      confirms the therapeutic efficacy of 5 mg of levocetirizine in improving symptoms
      of SAR, which was superior to 10 mg of montelukast.

PMID- 18814453
TI  - Onset of effect of budesonide and formoterol administered via one pressurized
      metered-dose inhaler in patients with asthma previously treated with inhaled
      corticosteroids.
AB  - BACKGROUND: Onset of bronchodilation of budesonide/formoterol in one pressurized
      metered-dose inhaler (pMDI) has not been evaluated in asthma. OBJECTIVE: To
      evaluate time to onset of clinically significant bronchodilation (> or = 15%
      improvement in forced expiratory volume in 1 second) and patient-perceived onset
      of effect (OE) in patients previously receiving inhaled corticosteroids. METHODS:
      In two 12-week studies, patients 12 years and older with moderate to severe
      (study 1; n = 596) and mild to moderate (study 2; n = 480) persistent asthma
      received budesonide/formoterol pMDI, budesonide pMDI plus formoterol dry powder
      inhaler (study 1 only), budesonide pMDI, formoterol dry powder inhaler, or
      placebo. Postdose time to 15% or greater improvement in forced expiratory volume
      in 1 second and patient-perceived OE (assessed in a subset of patients 18 years
      and older [study 1, n=553; study 2, n=405]) were evaluated [corrected] RESULTS:
      More budesonide/formoterol-treated patients achieved onset of clinically
      significant bronchodilation within 15 minutes (median, 13 minutes) of
      administration at randomization vs those taking budesonide or placebo (P < .001).
      More patients receiving budesonide/formoterol vs budesonide and placebo reported
      feeling their study medication begin to work right away (P < or = .004; end of
      week 1). Similar results (P < .001) were observed for patient satisfaction with
      how quickly they felt their medication begin to work (except
      budesonide/formoterol vs budesonide, study 1 [P = .073]). Time to onset of
      clinically significant bronchodilation and patient-perceived OE of
      budesonide/formoterol and formoterol were similar. CONCLUSION:
      Budesonide/formoterol demonstrated a more rapid onset of clinically significant
      bronchodilation and a greater percentage of patients who perceived their
      medication working right away vs budesonide or placebo.

PMID- 18814454
TI  - Frequency of acute systemic reactions in patients with allergic rhinitis and
      asthma treated with sublingual immunotherapy.
AB  - BACKGROUND: Several studies have demonstrated the efficacy and safety of
      sublingual immunotherapy in the treatment of respiratory allergy. OBJECTIVE: To
      determine the frequency of systemic adverse reactions in patients treated with
      standardized extracts of sublingual immunotherapy. METHODS: Allergic patients
      with rhinitis with or without asthma and sensitized to at least 1 allergen were
      included. Increasing doses of standardized allergens were administered until
      reaching an average dose accumulated of 7,200 U after 26 weeks of treatment.
      Adverse events were graded according to the European Academy of Allergy and
      Clinical Immunology immunotherapy position paper. RESULTS: Forty-three patients
      with a median age of 11 years (interquartile range, 8-20 years) were included.
      All the patients had allergic rhinitis, and 63% had asthma; they were sensitized
      mostly to Dermatophagoides pteronyssinus and Dermatophagoides farinae. Four
      patients (9%) presented with an immediate and 1 (2%) with a late systemic
      reaction. In total, 7 systemic reactions occurred in 23,154 doses, and all were
      associated with wheezing or worsening of nasal symptoms (grade 2); in addition, 1
      patient had angioedema and urticaria (grade 3). CONCLUSIONS: In this group,
      systemic reaction frequency was 11.6%, and all were classified as grade 2 or 3.
      Further assessments in larger samples of patients are required in the context of
      randomized controlled trials.

PMID- 18814455
TI  - Successful administration of a 1-day imported fire ant rush immunotherapy
      protocol.
AB  - BACKGROUND: Young children with a history of systemic reactions to imported fire
      ant (IFA) stings are at substantial risk of recurrent stings because of their
      maturational inability to practice appropriate avoidance techniques. OBJECTIVE:
      To present 3 cases in which patients 36 months or younger completed a 1-day rush
      immunotherapy (RIT) protocol with IFA whole-body extract (WBE). METHODS: The 1
      day RIT protocol used for these patients was modified from the Wilford Hall 2-day
      rush protocol previously published. A 1:1 vol/vol maintenance vial consisted of 1
      mL of IFA WBE and 9 mL of human serum albumin diluent in a 10-mL vial. RESULTS:
      All 3 patients had positive intradermal skin test results to IFA WBE. No systemic
      reactions occurred during the 1-day RIT. CONCLUSIONS: This case series provides
      data with which we can begin to assess the efficacy and safety of a 1-day IFA RIT
      protocol for the prevention of anaphylaxis in IFA allergic children. Further
      studies with larger numbers of patients are needed to confirm the findings.

PMID- 18814456
TI  - Cost-effectiveness of specific subcutaneous immunotherapy in patients with
      allergic rhinitis and allergic asthma.
AB  - BACKGROUND: Specific immunotherapy is the only potentially curative treatment in
      patients with allergic rhinitis and allergic asthma. Health economic evaluations
      on this treatment, particularly in a German context, are sparse. OBJECTIVE: To
      evaluate the cost-effectiveness of specific subcutaneous immunotherapy (SCIT) in
      addition to symptomatic treatment (ST) compared with ST alone in a German health
      care setting. METHODS: The analysis was performed as a health economic model
      calculation based on Markov models. In addition, we performed a concomitant
      expert board composed of allergy experts in pediatrics, dermatology, pneumology,
      and otolaryngology. The primary perspective of the study was societal. Additional
      sensitivity analyses were performed to prove our results for robustness. RESULTS:
      The SCIT and ST combination was associated with annual cost savings of Euro140
      per patient. After 10 years of disease duration, SCIT and ST reach the breakeven
      point. The overall incremental cost-effectiveness ratio (ICER) was Euro-19,787
      per quality-adjusted life-year (QALY), with a range that depended on patient age
      (adults, Euro-22,196; adolescents, Euro-14,747; children, Euro-12,750). From a
      third-party payer's perspective, SCIT was associated with slightly additional
      costs. Thus, the resulting ICER was Euro8,308 per QALY for all patients.
      CONCLUSIONS: Additional SCIT was associated with improved medical outcomes and
      cost savings compared with symptomatic treatment alone according to a societal
      perspective. Taking a European accepted ICER threshold of up to Euro50,000 per
      QALY into account, additional SCIT is considered clearly cost-effective compared
      with routine care in Germany. The degree of cost-effectiveness is strongly
      affected by costs related to SCIT and the target population receiving such
      treatment.

PMID- 18814457
TI  - Basic science for the practicing physician: gene expression microarrays.
AB  - OBJECTIVE: To provide a general overview of gene expression microarray technology
      and its relevance to physicians practicing allergy/immunology. DATA SOURCES: The
      PubMed interface to MEDLINE was searched for primary and review articles on gene
      expression microarrays. Specific articles on clinical applications of microarrays
      were retrieved, along with articles on use of microarrays in models of allergy,
      asthma, and immunologic diseases. STUDY SELECTION: The author's knowledge of the
      field was used to include sources of information other than those obtained
      through the MEDLINE search. RESULTS: A synopsis of gene expression microarray
      technology, with emphasis on the relevance to allergy, asthma, and immunology, is
      presented. CONCLUSIONS: Gene expression microarray technology allows
      investigators to measure gene expression across the genome. This has allowed
      researchers to improve our understanding of immunologic mechanisms in disease
      models. Initially used solely as a research tool, microarray-based clinical tests
      are now available, and many more are in development. Use of microarrays in
      allergy, asthma, and immunology will support the development of novel diagnostic
      tests for the physician and facilitate exploration of the basic mechanisms
      underlying allergic and immunologic diseases.

PMID- 18814458
TI  - Neuropsychiatric disorders during intranasal corticosteroid therapy.

PMID- 18814459
TI  - Fixed drug eruption caused by amoxicillin-clavulanic.

PMID- 18814460
TI  - Effects of anxiety on task switching: evidence from the mixed antisaccade task.
AB  - According to the attentional control theory of anxiety (Eysenck, Derakshan,
      Santos, & Calvo, 2007), anxiety impairs performance on cognitive tasks that
      involve the shifting function of working memory. This hypothesis was tested using
      a mixed antisaccade paradigm, in which participants performed single-task and
      mixed-task versions of the paradigm. The single task involved the completion of
      separate blocks of anti- and prosaccade trials, whereas in the mixed task,
      participants completed anti- and prosaccade trials in a random order within
      blocks. Analysis of switch costs showed that high-anxious individuals did not
      exhibit the commonly reported paradoxical improvement in saccade latency, whereas
      low-anxious individuals did. The findings are discussed within the framework of
      attentional control theory.

PMID- 18814461
TI  - Anxiety and cognitive efficiency: differential modulation of transient and
      sustained neural activity during a working memory task.
AB  - According to the processing-efficiency hypothesis (Eysenck, Derakshan, Santos, &
      Calvo, 2007), anxious individuals are thought to require greater activation of
      brain systems supporting cognitive control (e.g.,dorsolateral prefrontal cortex;
      DLPFC) in order to maintain equivalent performance to nonanxious subjects. A
      recent theory of cognitive control (Braver, Gray, & Burgess, 2007) has proposed
      that reduced cognitive efficiency might occur as a result of changes in the
      temporal dynamics of DLPFC recruitment. In this study, we used a mixed blocked/
      event-related fMRI design to track transient and sustained activity in DLPFC
      while high- and low-anxious participants performed a working memory task. The
      task was performed after the participants viewed videos designed to induce
      neutral or anxiety-related moods. After the neutral video, the high-anxious
      participants had reduced sustained but increased transient activation in working
      memory areas, in comparison with low-anxious participants. The high-anxious group
      also showed extensive reductions in sustained activation of "default-network"
      areas (possible deactivation). After the negative video,the low-anxiety group
      shifted their activation dynamics in cognitive control regions to resemble those
      of the high-anxious group. These results suggest that reduced cognitive control
      in anxiety might be due to a transient, rather than sustained, pattern of working
      memory recruitment. Supplementary information for this study may be found at
      www.psychonomic.org/archive.

PMID- 18814462
TI  - Intact implicit and reduced explicit memory for negative self-related information
      in repressive coping.
AB  - Voluntary emotional memory control has recently been shown to involve prefrontal
      down-regulation of medial temporal lobe activity during memory retrieval.
      However, little is known about instances of uninstructed, naturally occurring
      forgetting. In the present study, we examined whether memory suppression extends
      to involuntary, uninstructed down-regulation of memory in individuals thought to
      be experts in forgetting negative memories--those with a repressive coping style.
      We contrasted explicit and implicit memory for negative information in repressor
      and nonrepressor groups and examined whether self-relevance is a moderating
      variable. To delineate the specificity of repressors' selective memory
      reductions, we contrasted encoding and retrieval of emotional words as a function
      of self-reference, subjective self-relevance, and explicitness of the memory task
      in nonrepressors and repressors. Self-descriptiveness judgments, lexical
      decisions (implicit memory), and free recall (explicit memory) were investigated.
      Repressors had selectively lowered free recall only for negative, self-relevant
      information. Their implicit memory for the same information was unaffected. This
      pattern suggests that regulation of emotional memory in repressive individuals is
      a case of motivated forgetting, possibly sharing much of the neural underpinnings
      of voluntary memory suppression.

PMID- 18814463
TI  - Recognition of facial expressions is influenced by emotional scene gist.
AB  - Recognition of facial expressions has traditionally been investigated by
      presenting facial expressions without any context information. However, we rarely
      encounter an isolated facial expression; usually, we perceive a person's facial
      reaction as part of the surrounding context. In the present study, we addressed
      the question of whether emotional scenes influence the explicit recognition of
      facial expressions. In three experiments, participants were required to
      categorize facial expressions (disgust, fear, happiness) that were shown against
      backgrounds of natural scenes with either a congruent or an incongruent emotional
      significance. A significant interaction was found between facial expressions and
      the emotional content of the scenes, showing a response advantage for facial
      expressions accompanied by congruent scenes. This advantage was robust against
      increasing task load. Taken together, the results show that the surrounding scene
      is an important factor in recognizing facial expressions.

PMID- 18814464
TI  - Examinations of identity invariance in facial expression adaptation.
AB  - Faces provide a wealth of information essential to social interaction, including
      both static features, such as identity, and dynamic features, such as emotional
      state. Classic models of face perception propose separate neural-processing
      routes for identity and facial expression (Bruce & Young, 1986), but more recent
      models suggest that these routes are not independent of each other (Calder &
      Young, 2005). Using a perceptual adaptation paradigm in the present study, we
      attempted to further examine the nature of the relation between the neural
      representations of identity and emotional expression. In Experiment 1, adaptation
      to the basic emotions of anger, surprise, disgust, and fear resulted in
      significantly biased perception away from the adapting expression. A
      significantly decreased aftereffect was observed when the adapting and the test
      faces differed in identity. With a statistical model that separated surface
      texture and reflectance from underlying expression geometry, Experiment 2 showed
      a similar decrease in adaptation when the face stimuli had identical underlying
      prototypical geometry but differed in the static surface features supporting
      identity. These results provide evidence that expression adaptation depends on
      perceptual features important for identity processing and thus suggest at least
      partly overlapping neural processing of identity and facial expression.

PMID- 18814465
TI  - Depth of facial expression processing depends on stimulus visibility: behavioral
      and electrophysiological evidence of priming effects.
AB  - Participants performed a priming task during which emotional faces served as
      prime stimuli and emotional words served as targets. Prime-target pairs were
      congruent or incongruent, and two levels of prime visibility were obtained by
      varying the duration of the masked primes. To probe a neural signature of the
      impact of the masked primes, lateralized readiness potentials (LRPs) were
      recorded over motor cortex. In the high-visibility condition, responses to word
      targets were faster when the prime-target pairs were congruent than when they
      were incongruent, providing evidence of priming effects. In line with the
      behavioral results, the electrophysiological data showed that high-visibility
      face primes resulted in LRP differences between congruent and incongruent trials,
      suggesting that prime stimuli initiated motor preparation. Contrary to the above
      pattern, no evidence for reaction time or LRP differences was observed in the low
      visibility condition, revealing that the depth of facial expression processing is
      dependent on stimulus visibility.

PMID- 18814466
TI  - Differential activation patterns of occipital and prefrontal cortices during
      motion processing: evidence from normal and schizophrenic brains.
AB  - Visual motion perception is normally mediated by neural processing in the
      posterior cortex. Focal damage to the middle temporal area (MT), a posterior
      extrastriate region, induces motion perception impairment. It is unclear,
      however, how more broadly distributed cortical dysfunction affects this visual
      behavior and its neural substrates. Schizophrenia manifests itself in a variety
      of behavioral and perceptual abnormalities that have proved difficult to
      understand through a dysfunction of any single brain system. One of these
      perceptual abnormalities involves impaired motion perception. Motion processing
      provides an opportunity to clarify the roles of multiple cortical networks in
      both healthy and schizophrenic brains. Using fMRI, we measured cortical
      activation while participants performed two visual motion tasks (direction
      discrimination and speed discrimination) and one nonmotion task (contrast
      discrimination). Normal controls showed robust cortical activation (BOLD signal
      changes) in MT during the direction and speed discrimination tasks, documenting
      primary processing of sensory input in this posterior region. In patients with
      schizophrenia, cortical activation was significantly reduced in MT and
      significantly increased in the inferior convexity of the prefrontal cortex, an
      area that is normally involved in higher level cognitive processing. This shift
      in cortical responses from posterior to prefrontal regions suggests that motion
      perception in schizophrenia is associated with both deficient sensory processing
      and compensatory cognitive processing. Furthermore, this result provides evidence
      that in the context of broadly distributed cortical dysfunction, the usual
      functional specificity of the cortex becomes modified, even across the domains of
      sensory and cognitive processing.

PMID- 18814468
TI  - Cortical regions activated by the subjective sense of perceptual coherence of
      environmental sounds: a proposal for a neuroscience of intuition.
AB  - According to the Oxford English Dictionary, intuition is "the ability to
      understand or know something immediately, without conscious reasoning." In other
      words, people continuously, without conscious attention, recognize patterns in
      the stream of sensations that impinge upon them. The result is a vague perception
      of coherence, which subsequently biases thought and behavior accordingly. Within
      the visual domain, research using paradigms with difficult recognition has
      suggested that the orbitofrontal cortex (OFC) serves as a fast detector and
      predictor of potential content that utilizes coarse facets of the input. To
      investigate whether the OFC is crucial in biasing task-specific processing, and
      hence subserves intuitive judgments in various modalities, we used a difficult
      recognition paradigm in the auditory domain. Participants were presented with
      short sequences of distorted, nonverbal, environmental sounds and had to perform
      a sound categorization task. Imaging results revealed rostral medial OFC
      activation for such auditory intuitive coherence judgments. By means of a
      conjunction analysis between the present results and those from a previous study
      on visual intuitive coherence judgments, the rostral medial OFC was shown to be
      activated via both modalities. We conclude that rostral OFC activation during
      intuitive coherence judgments subserves the detection of potential content on the
      basis of only coarse facets of the input.

PMID- 18814467
TI  - Striatal outcome processing in healthy aging.
AB  - Functional MRI of young adults has implicated the striatum in the processing of
      rewarding and punishing events. To date, only two published experiments (Samanez
      Larkin et al., 2007; Schott et al., 2007) have explored similar phenomena in
      older adults, with both studies emphasizing the anticipation of monetary
      outcomes. To better understand older participants' striatal responses to
      delivered outcomes, we engaged 20 older adults and 13 younger adults in a card
      guessing task that rewarded correct guesses with monetary gain and punished
      incorrect guesses with monetary loss. Overall, the older adults retained most of
      the typical features of the striatal response, so that activity in the caudate
      head showed reliable differentiation between rewards and punishments during the 6
      to 9-sec postoutcome window. Comparison of the older and younger adults also
      pointed to some potential aging effects on outcome activity, including reductions
      in the magnitude and extent of striatal activation, and a trend for the older
      adults to show a decreased early punishment response. In sum, our data suggest
      that the signaling of outcome valence remains relatively stable into late
      adulthood, although more research is needed to understand some subtle changes
      that might occur across the life span.

PMID- 18814469
TI  - It all sounds the same to me: sequential ERP and behavioral effects during pitch
      and harmonicity judgments.
AB  - The representation of complex sounds was examined by comparing both behavioral
      and event-related brain potentials (ERPs) to the change or repetition of
      fundamental frequency (f0) and harmonicity. In the pitch task, participants were
      asked to categorize the incoming stimulus as either low or high, regardless of
      harmonicity, and in the harmonicity task, participants indicated whether the
      stimulus was tuned or mistuned, regardless of pitch. Over three experiments,
      participants were faster in responding to pitch than to harmonicity. As a result
      of this asymmetry, behavioral and ERP data showed that irrelevant changes in
      harmonicity had little impact on performance during the pitch task, whereas
      harmonicity judgments were impeded by irrelevant changes in f0. These data are
      consistent with both general horse-race accounts of processing and specific
      accounts of mistuning detection that posit prior f0 registration. In addition,
      ERP components N2 and P3 were modulated by both intertrial contingency and task
      instructions, revealing the further influence of top-down mechanisms on
      concurrent sound segregation.

PMID- 18814470
TI  - Health groups limber up to influence the political agenda.

PMID- 18814471
TI  - It takes time to get results.
AB  - The NHS National Programme for Information Technology in England has attracted
      many critics but has the potential to revolutionise patient care.

PMID- 18814472
TI  - Efficiency downgrade.
AB  - Despite problems, the NH National Programme for Information Technology could
      still deliver significant benefits if implemented correctly.

PMID- 18814473
TI  - Capacity for progress.
AB  - Information technology is set to transform health services in low resource
      countries, benefits which could filter down to their wealthier counterparts.

PMID- 18814474
TI  - Measure of success.

PMID- 18814475
TI  - Venous access in oncology and haematology patients: Part two.
AB  - AIM: To assess the validity and inter-rater reliability of two tools, Venous
      Assessment Tool (VAT) and Deciding on IntraVenous Access (DIVA), using thematic
      analysis of feedback from nurses who used the tools, METHOD: Analysis methods
      used in grounded theory were employed to investigate the written feedback
      provided by nurses. Inter-rater reliability was tested statistically using
      percentage agreement and the kappa (K) statistic. FINDINGS: Thematic analysis of
      the nurses' feedback generated themes concerning the role of clinical judgement,
      how theory translates to practice and the role of patient preference when using
      VAT and DIVA. Exploring these themes confirmed the validity of the tools and
      highlighted the importance of these considerations when evaluating the usefulness
      of assessment tools in the clinical environment. When VAT was used by a group of
      nurses to assess patients, the strength of agreement statistically was
      'moderate'. When using DIVA, the tool demonstrated 'very good' agreement
      statistically. CONCLUSION: When used with oncology and haematology patients, VAT
      and DIVA have been shown to generate agreement among the nurses who used them
      beyond that which would be expected by chance. As the only tools of this kind
      with evidence of inter-rater reliability, they provide clinicians with a useful
      resource which can be used in practice or research. However, the use of
      assessment tools cannot replace clinical judgement or override the preferences of
      patients.

PMID- 18814476
TI  - Deterioration in hospital patients: early signs and appropriate actions.
AB  - Early identification of clinical deterioration in hospitalised patients is
      important to prevent subsequent cardiopulmonary arrest and reduce mortality.
      Understanding where and why the care process fails, resulting in the inability to
      recognise patient deterioration, can help healthcare staff and organisations to
      prioritise and improve patient safety. This article is based on interagency work
      undertaken by the National Patient Safety Agency and guidelines produced by the
      National Institute for Health and Clinical Excellence.

PMID- 18814477
TI  - Haematuria: causes and management.
AB  - Most nurses are familiar with testing urine and many do so daily. The urine
      dipstick can reveal many abnormalities. The purpose of this article is to ensure
      that nurses are aware of the possible significance of finding blood in a
      patient's urine.

PMID- 18814478
TI  - Infusion therapy.

PMID- 18814479
TI  - Learning to change.

PMID- 18814480
TI  - Knowledge swap.

PMID- 18814481
TI  - Greater flexibility for learning.

PMID- 18814482
TI  - Prevention of postoperative microbial infection by synbiotics.
AB  - Prevention of infectious complications after major surgeries including those for
      cancer has been a major concern in the clinical field. To overcome this problem,
      probiotics and synbiotics (combination of probiotics and prebiotics have recently
      been introduced for post-operative treatment. Clinical application of synbiotics
      in severe cases, such as severe pediatric surgical cases, acute pancreatitis,
      liver transplantation, and biliary cancer, has been reported. The present article
      deals with the clinical effect of such synbiotic therapies for the patients under
      emergency medical care, and discusses the possible mechanism of action and
      prospect of synbiotic therapy.

PMID- 18814483
TI  - Effect of vitamin E on alcohol-induced changes in oxidative stress and expression
      of transcription factors NFkappaB and AP-1 in mice brain cerebral hemispheres.
AB  - Redox sensitive transcription factors nuclear factor kappaB (NF-kappaB) and
      activator protein-1 are involved in the pathogenesis of alcohol-induced
      disorders. Because of its antioxidative properties, vitamin E may help prevent
      oxidative stress-induced disorders. The aim of the present study was to delineate
      the molecular mechanisms associated with alcohol-induced oxidative stress and to
      see whether vitamin E supplementation counters the alcohol-induced adverse
      effects. The results showed that vitamin E supplementation restored the redox
      status and thus prevented the alcohol-induced oxidative stress. Further
      measurements of the mRNA expressions of cjun, cfos, p65 (NFkappaB) indicated an
      increase in their expression during oxidative stress. Although Vit E inhibited
      NFkappaB activation, it stimulated AP1 expression. The results support the
      findings that alcohol induces oxidative stress in nervous tissue. The data
      further show that vitamin E can mitigate the toxic effects of alcohol and thus
      can be suitable as a potential therapeutic agent for alcohol-induced oxidative
      damage in brain.

PMID- 18814484
TI  - Modulation of CYP4502E1 and oxidative stress by testosterone in liver and kidney
      of benzene treated rats.
AB  - Bilateral castration increased lipid peroxidation and consequently reduced
      glutathione in both liver and kidney. Testosterone administration reduced lipid
      peroxidation in the liver of castrated and benzene treated rats, however, reduced
      glutathione status could not be restored. Benzene depleted CYP4502E1 in castrated
      rats, however, the enzyme was restored in liver and kidney both after
      testosterone treatment. The results suggest that testosterone affects the
      metabolism and disposition of benzene by influencing CYP4502E1. Other hormonal
      and cellular/molecular factors may also alter the actions of testosterone.
      Testosterone dependent mechanism of toxicity of benzene in the liver and kidney
      has been discussed.

PMID- 18814485
TI  - Rapid detection and characterization of Chikungunya virus by RT-PCR in febrile
      patients from Kerala, India.
AB  - There has been a resurgence and prevalence of fever with symptoms of Chikungunya
      (CHIK) and increased death toll in Kerala, the southern-most state of India. The
      objective of this study was to develop a rapid detection method to determine the
      presence of CHIK- virus in the serum samples collected from febrile patients in
      Kerala, India. Serum specimens were analyzed for CHIK viral RNA by RT-PCR using
      primers specific for nsP1 and E1 genes. Five out of twenty clinical samples were
      positive for CHIK virus. The partial sequences of the E1 and nsP1 genes of the
      strain, IndKL01 were highly similar to the Reunion strains and the recently
      isolated Indian strains. A novel substitution, A148V, was detected in the E1 gene
      of the isolate, IndKL02. The detection procedure used in this study was simple,
      sensitive and rapid (less than 4 hr). This result suggests that CHIK viruses
      similar to the Reunion strains, which had resulted in high morbidity and
      mortality rates, may have caused the recent Chikungunya outbreak in India. The
      effect of the variant, E1-A148V, in the virulence and the rate of transmission of
      the virus deserves further investigation.

PMID- 18814486
TI  - Evaluation of four methods of DNA recovery from Mycobacterium avium subspecies
      paratuberculosis present in intestine tissue of goats and comparative sensitivity
      of IS900 PCR with respect to culture for diagnosis of Johne's disease.
AB  - Low sensitivity of PCR reaction for detection of Mycoobacterium avium subspecies
      paratuberculosis (MAP) in tissues and fecal samples is mainly attributed to false
      negative results. Present study was undertaken to compare four methods of DNA
      isolation from tissues of infected animals and to determine most sensitive
      protocol for the recovery of DNA, suitable for IS900 PCR based detection of
      Johne's disease infection. Method I, the traditional van Soolingen2 method of DNA
      isolation was adopted for the isolation of DNA from tissues. Method II was
      modification (hexadecyl pyridinium chloride-HPC treatment) of van Soolingen2
      method. Method III was traditional tissue DNA isolation method based on tissue
      lysis buffer. Method IV was modification of method III (HPC treatment). Using
      four methods of DNA isolation from 25 intestinal tissues of clinically infected
      goats, DNA was isolated from 15 (60.0%), 18 (72.0%), 13 (52.0%) and 13 (52.0%)
      tissues using method I, II, III and IV, respectively. All isolated DNA
      preparations were positive for MAP in IS900 PCR. HPC treatment enhanced the
      recovery of DNA from tissues of infected animals using method II. Therefore,
      method II can improve the diagnosis MAP infection using IS900 PCR.

PMID- 18814487
TI  - Effect of Manuka honey and sulfasalazine in combination to promote antioxidant
      defense system in experimentally induced ulcerative colitis model in rats.
AB  - Manuka honey (MH, 5g/kg) provided protection against trinitro-benzo-sulphonic
      acid induced colonic damage. Combination therapy (MH+sulfasalazine) also reduced
      colonic inflammation and all the biochemical parameters were significant compared
      to control and MH alone treated group. Combination therapy showed additive effect
      of the MH which restored lipid peroxidation and improvement of antioxidant
      parameters. Morphological and histological scores were significantly reduced in
      combination groups. In inflammatory model of colitis, oral administration of MH
      (5g/kg) and combination with sulfasalazine (360 mg/kg) with MH (5g/kg)
      significantly reduced the colonic inflammation. The results indicate the additive
      effect of Manuka honey with sulfasalazine in colitis.

PMID- 18814488
TI  - Nootropic activity of tuber extract of Pueraria tuberosa (Roxb).
AB  - Nootropic effect of alcoholic (ALE; 50, 75, 100 mg/kg) and aqueous (AQE; 100,
      200, 400 mg/kg) extracts of P. tuberosa was evaluated by using Elevated Plus Maze
      (EPM), scopolamine-induced amnesia (SIA), diazepam-induced amnesia (DIA),
      clonidine-induced (NA-mediated) hypothermia (CIH), lithium-induced (5-HT
      mediated) head twitches (LIH) and haloperidol-induced (DA- mediated) catalepsy
      (HIC) models. Piracetam was used as the standard drug. A significant increase in
      inflexion ratio (IR) was recorded in EPM, SIA and DIA models. A significant
      reversal effect was observed on rectal temperature in CIH model, reduction of
      head twitches in LIH models. However no significant reduction in catalepsy scores
      in HIC models were observed with test extracts and standard piracetam. The
      results indicate that nootropic activity observed with ALE and AQE of tuber
      extracts of P. tuberosa could be through improved learning and memory either by
      augmenting the noradrenaline (NA) transmission or by interfering with 5
      hydroxytryptamine (5-HT) release. Further, the extracts neither facilitated nor
      blocked release of the dopamine (DA). Thus ALE and AQE elicited significant
      nootropic effect in mice and rats by interacting with cholinergic, GABAnergic,
      adrenergic and serotonergic systems. Phytoconstituents like flavonoids have been
      reported for their nootropic effect and these are present in both ALE and AQE
      extracts of tubers of P. tuberosa (Roxb) and these active principles may be
      responsible for nootropic activity.

PMID- 18814489
TI  - Antidiabetic activity of a polyherbal formulation (DRF/AY/5001).
AB  - The herbal formulation, DRF/AY/5001, elicits hypoglycemic/antidiabetic effects in
      both normal and experimentally induced hyperglycemic (epinephrine and alloxan)
      rats. Further, herbal formulation treatment can significantly alter the pattern
      of glucose tolerance in normal and diabetic rats. It is possible that the herbal
      formulation may act through both, pancreatic and extra-pancreatic mechanism(s).
      The DRF/AY/5001 also elicited a significant antioxidant effect in alloxan
      diabetic rats as reflected by its ability to inhibit lipid peroxidation and to
      elevate the enzymatic antioxidants in pancreatic tissue. The histopathological
      studies during the long-term treatment have shown to ameliorate the alloxan
      induced histological damage of islets of Langerhans. The inhibitory effects on
      biochemical and histological parameters induced by herbal formulation at a dose
      of 600 mg/kg were almost comparable to that of standard drug, glibenclamide (4
      mg/kg). The present study demonstrates that herbal formulation exhibits
      promisisng antidiabetic activity and helps to maintain good glycemic and
      metabolic control.

PMID- 18814490
TI  - Antihyperglycaemic activity of aqueous extract of Embelia ribes Burm in
      streptozotocin-induced diabetic rats.
AB  - Forty days of orally feeding the aqueous E. ribes extract (100 and 200 mg/kg) to
      streptozotocin (40 mg/kg, iv, single dose) induced diabetic rats produced
      significant decrease in heart rate, systolic blood pressure, blood glucose, blood
      glycosylated hemoglobin, serum lactate dehydrogenase, creatine kinase and
      increase in blood glutathione levels as compared to pathogenic diabetic rats.
      Further, the extract significantly decreased the levels of pancreatic lipid
      peroxides and increased the levels of pancreatic superoxide dismutase, catalase
      and glutathione. The results suggest that aqueous E. ribes extract exhibits a
      significant blood glucose and blood pressure lowering potential. Further, it
      enhances endogenous antioxidant defense against free radicals produced under
      hyperglycaemic conditions, thereby, seemingly protects the pancreatic beta-cells
      against loss in streptozotocin induced diabetic rats.

PMID- 18814491
TI  - Hypoglycemic potential of Morus indica. L and Costus igneus. Nak.--a preliminary
      study.
AB  - Powdered leaves (500 mg/kg body weight) of medicinal plants M. indica and C.
      igneus known to possess therapeutic effect were supplemented to streptozotocin
      induced diabetic rats. Leaf powders of both the plants were able to reduce blood
      glucose levels in the animals by 38 and 21% respectively after 15 days of
      supplementation. The preliminary results suggest that both the plants possess
      potent hypoglycemic activity.

PMID- 18814492
TI  - Assessing the sensibility of two clinical decision support systems.
AB  - Clinicians in Emergency Medicine (EM) are increasingly exposed to guidelines and
      treatment recommendations. To help access and recall these recommendations,
      electronic Clinical Decision Support Systems (CDSS) have been developed. This
      study examined the use and sensibility of two CDSS designed for emergency
      physicians. CDDS for community acquired pneumonia (CAP) and neutropenic fever
      (NF) were developed by multidisciplinary teams and have been accessed via an
      intranet-based homepage (eCPG) for several years. Sensibility is a term coined by
      Feinstein that describes common sense aspects of a survey instrument. It was
      modified by emergency researchers to include four main headings: (1)
      Appropriateness; (2) Objectivity; (3) Content; and (4) Discriminative Power.
      Sensibility surveys were developed using an iterative approach for both the CAP
      and NF CDSS and distributed to all 25 emergency physicians at one Canadian site.
      The overall response rate was 88%. Respondents were 88% male and 83% were less
      than 40; all were attending EM physicians with specialty designations. A number
      reported never having used the CAP (21%) or NF (33%) CDSS; 54% (CAP) and 21% (NF)
      of respondents had used the respective CDSS less than 10 times. Overall, both
      CDSS were rated highly by users with a mean response of 4.95 (SD 0.56) for CAP
      and 5.62 (SD 0.62) for NF on a seven-point Likert scale. The majority or
      respondents (CAP 59%, NF 80%) felt that the NF CDSS was more likely than the CAP
      CDSS to decrease the chances of making a medical error in medication dose,
      antibiotic choice or patient disposition (4.61 vs. 5.81, p=0.008). Despite being
      in place for several years, CDSS for CAP and NF are not used by all EM
      clinicians. Users were generally satisfied with the CDSS and felt that the NF was
      more likely than the CAP CDSS to decrease medical errors. Additional research is
      required to determine the barriers to CDSS use.

PMID- 18814493
TI  - A new method for diagnosis of cirrhosis disease: complex-valued artificial neural
      network.
AB  - In this study, complex-valued artificial neural network (CVANN) that is a new
      technique for biomedical pattern classification was proposed for classifying
      portal vein Doppler signals recorded from 54 patients with cirrhosis and 36
      healthy subjects. Fast Fourier transform values of Doppler signals were
      calculated for pre-processing and obtained values, which include real and
      imaginary components, were used as the inputs of the CVANN for classification of
      Doppler signals. Classification results of CVANN show that Doppler signals were
      classified successfully with 100% correct classification rate using leave-one-out
      cross-validation. Besides, CVANN has 100% sensitivity and 100% specificity. These
      results were found to be compliant with the expected results that are derived
      from physician's direct diagnosis. This method would be to assist the physician
      to make the final decision.

PMID- 18814494
TI  - Pairwise ANFIS approach to determining the disorder degree of obstructive sleep
      apnea syndrome.
AB  - Obstructive sleep apnea syndrome (OSAS) is an important disease that affects both
      the right and the left cardiac ventricle. This paper presents a novel
      classification method called pairwise ANFIS based on Adaptive Neuro-Fuzzy
      Inference System (ANFIS) and one against all method for detecting the obstructive
      sleep apnea syndrome. In order to extract the features related with OSAS, we have
      used the clinical features obtained from Polysomnography device as a diagnostic
      tool for obstructive sleep apnea (OSA) in patients clinically suspected of
      suffering from this disease. The clinical features obtained from Polysomnography
      Reports are Arousals Index (ARI), Apnea and Hypoapnea Index (AHI), SaO2 minimum
      value in stage of REM, and Percent Sleep Time (PST) in stage of SaO2 intervals
      bigger than 89%. Since ANFIS has output with one class, we have extended the
      output of ANFIS to multi class by means of one against all method to diagnose the
      OSAS that has four classes consisting of normal (25 subjects), mild OSAS (AHI=5
      15 and 14 subjects), middle OSAS (AHI<15-30 and 18 subjects), and heavy OSAS
      (AHI>30 and 26 subjects). The classification accuracy, sensitivity and specifity
      analysis, mean square error, and confusion matrix have been used to test the
      performance of proposed method. The obtained classification accuracies are
      82.92%, 82.92%, 85.36%, and 87.80% for each class including normal, mild OSAS,
      middle OSAS, and heavy OSAS using ANFIS with one against all method with 50-50%
      train-test split, respectively. Combining ANFIS and one against all method that
      is firstly proposed by us was firstly applied for diagnosing the OSAS. The
      proposed method has produced very promising results in the detecting the
      obstructive sleep apnea syndrome.

PMID- 18814495
TI  - Process modeling of emergency department patient flow: effect of patient length
      of stay on ED diversion.
AB  - A discreet event simulation methodology has been used to establish a quantitative
      relationship between Emergency Department (ED) performance characteristics, such
      as percent of time on ambulance diversion and the number of patients in queue in
      the waiting room, and the upper limits of patient length of stay (LOS). A
      simulation process model of ED patient flow has been developed that took into
      account a significant difference between LOS distributions of patients discharged
      home and patients admitted into the hospital. Using simulation model it has been
      identified that ED diversion could be negligible (less than approximately 0.5%)
      if patients discharged home stay in ED not more than 5 h, and patients admitted
      into the hospital stay in ED not more than 6 h Using full factorial design of
      experiments with two factors and the model's predicted percent diversion as a
      response function, other combinations of LOS upper limits have been determined
      that would result in low ED percent diversion as well. It has also been
      determined that if the number of patients exceeds 11 in queue in ED waiting room
      then the diversion percent is rapidly increasing.

PMID- 18814496
TI  - A radial basis function neural network model for classification of epilepsy using
      EEG signals.
AB  - Epilepsy is a disorder of cortical excitability and still an important medical
      problem. The correct diagnosis of a patient's epilepsy syndrome clarifies the
      choice of drug treatment and also allows an accurate assessment of prognosis in
      many cases. The aim of this study is to evaluate epileptic patients and classify
      epilepsy groups such as partial and primary generalized epilepsy by using Radial
      Basis Function Neural Network (RBFNN) and Multilayer Perceptron Neural Network
      (MLPNNs). Four hundred eighteen patients with epilepsy diagnoses according to
      International League against Epilepsy (ILAE 1981) were included in this study.
      The correct classification of this data was performed by two expert neurologists
      before they were executed by neural networks. The neural networks were trained by
      the parameters obtained from the EEG signals and clinic properties of the
      patients. Experimental results show that the predictions of both neural network
      models are very satisfying for learning data sets. According to test results,
      RBFNN (total classification accuracy = 95.2%) has classified more successfully
      when compared with MLPNN (total classification accuracy = 89.2%). These results
      indicate that RBFNN model may be used in clinical studies as a decision support
      tool to confirm the classification of epilepsy groups after the model is
      developed.

PMID- 18814497
TI  - Software development for the analysis of heartbeat sounds with LabVIEW in
      diagnosis of cardiovascular disease.
AB  - In this paper, a time-frequency spectral analysis software (Heart Sound Analyzer)
      for the computer-aided analysis of cardiac sounds has been developed with
      LabVIEW. Software modules reveal important information for cardiovascular
      disorders, it can also assist to general physicians to come up with more accurate
      and reliable diagnosis at early stages. Heart sound analyzer (HSA) software can
      overcome the deficiency of expert doctors and help them in rural as well as urban
      clinics and hospitals. HSA has two main blocks: data acquisition and
      preprocessing, time-frequency spectral analyses. The heart sounds are first
      acquired using a modified stethoscope which has an electret microphone in it.
      Then, the signals are analysed using the time-frequency/scale spectral analysis
      techniques such as STFT, Wigner-Ville distribution and wavelet transforms. HSA
      modules have been tested with real heart sounds from 35 volunteers and proved to
      be quite efficient and robust while dealing with a large variety of pathological
      conditions.

PMID- 18814498
TI  - A data capture system for outcomes studies that integrates with electronic health
      records: development and potential uses.
AB  - In conventional clinical studies, the costs of data management for quality
      control tend to be high and collecting paper-based case report forms (CRFs) tends
      to be burdensome, because paper-based CRFs must be developed and filled out for
      each clinical study protocol. Use of electronic health records for this purpose
      could result in reductions in cost and improvements in data quality in clinical
      studies. The purpose of this study was to develop a data capture system for
      observational cancer clinical studies (i.e. outcomes studies) that would
      integrate with an electronic health records system, to enable evaluation of
      patient prognosis, prognostic factors, outcomes and drug safety. At the
      Outpatient Oncology Unit of Kyoto University Hospital, we developed a data
      capture system that includes a cancer clinical database system and a data
      warehouse for outcomes studies. We expect that our new system will reduce the
      costs of data management and analysis and improve the quality of data in clinical
      studies.

PMID- 18814499
TI  - A study on chronic obstructive pulmonary disease diagnosis using multilayer
      neural networks.
AB  - Chronic Obstructive Pulmonary Disease (COPD) is a disease state characterized by
      airflow limitation that is not fully reversible. The airflow limitation is
      usually both progressive and associated with an abnormal inflammatory response of
      the lungs to noxious particles or gases. COPD is important health problem and one
      of the most common illnesses in Turkey. It is generally accepted that cigarette
      smoking is the most important risk factor and genetic factors are believed to
      play a role in the individual susceptibility. In this study, a study on COPD
      diagnosis was realized by using multilayer neural networks (MLNN). For this
      purpose, two different MLNN structures were used. One of the structures was the
      MLNN with one hidden layer and the other was the MLNN with two hidden layers.
      Back propagation with momentum and Levenberg-Marquardt algorithms were used for
      the training of the neural networks. The COPD dataset were prepared from a chest
      diseases hospital's database using patient's epicrisis reports.

PMID- 18814500
TI  - Monitoring of physiological parameters from multiple patients using wireless
      sensor network.
AB  - This paper presents a wireless sensor network system that has the capability to
      monitor physiological parameters from multiple patient bodies. The system uses
      the Medical Implant Communication Service band between the sensor nodes and a
      remote central control unit (CCU) that behaves as a base station. The CCU
      communicates with another network standard (the internet or a mobile network) for
      a long distance data transfer. The proposed system offers mobility to patients
      and flexibility to medical staff to obtain patient's physiological data on demand
      basis via Internet. A prototype sensor network including hardware, firmware and
      software designs has been implemented and tested. The developed system has been
      optimized for power consumption by having the nodes sleep when there is no
      communication via a bidirectional communication.

PMID- 18814501
TI  - [Total antioxidant blood capacity in patients with type 2 diabetes mellitus and
      distal symmetrical polyneuropathy].
AB  - BACKGROUND/AIM: Reduced systemic antioxidant defence is considerd to play an
      important mediating role in pathogenesis of diabetic neuropathy. The aim of this
      study was to evaluate if the total antioxidant blood capacity (TAC) is reduced in
      patients with type 2 diabetes mellitus (DM) and diabetic distal symmetrical
      polyneuropathy (DDSP) and to correlate this antioxidant capacity with the degree
      of peripheral nerve dysfunction. METHODS: This study involved 100 patients with
      type 2 DM and signs of DDSP, as well as the control group of 50 healthy subjects.
      The evaluation of DDSP was based on physical examination and nerve conduction
      studies. The degree of peripheral nerve dysfunction was estimated by scoring and
      analysing sensory and motor nerve conduction parameters (distal latency and
      amplitude of evoked potential, conduction velocity). Laboratory analyses involved
      blood glucose and HbA1C levels, as well as plasma TAC. RESULTS: Blood glucose and
      HbA1C level was significantly higher in the patients than in the control group (p
      < 0.0001). The TAC was depleted in the diabetic group and the depletion was
      statistically significant (p < 0.0001). There was no significant correlation
      between the TAC and the serum glucose level, TAC and HbA1C level as well as
      between TAC and the duration of DM. There was no significant correlation between
      TAC and peripheral nerve conduction parameters. CONCLUSION: Total antioxidant
      blood capacity is reduced in patients with DDSP, but it does not correlate with
      blood sugar level, with the duration of DM or with the degree of functional nerve
      damage. These results show a reduced systemic antioxidant defence in patients
      with type 2 DM and DDSP. However, it is still unclear to what extent the
      oxidative stress is a contributing factor or leading cause of diabetic
      neuropathy, suggesting that further studies are necessary.

PMID- 18814502
TI  - [Asymptomatic renal damages in persons with chronic professional exposure to
      elementary mercury low concentrations].
AB  - BACKGROUND/AIM: Any forms of mercury have toxic action on the majority of organs,
      especially kidneys. The major source of professional exposure to mercury are
      departments for the production of chlorine which use mercury as catode. The aim
      of the study was to prove that chronic exposure to elementary mercury low
      concentrations could cause asymptomatic damages of the kidneys. METHODS: A total
      of 40 workers from the factory ,,HIP Petrohemija" Pancevo, of the mean age 45+/-8
      years, who were exposed to the effects of mercury for more than 20 years within
      the production procedure, and 20 workers from the factory "Panonijaplast"
      Pancevo, of the mean age 44+/-7 years, who were not exposed to mercury nor to
      other nephrotoxic agents, were submitted to laboratory analysis, renal function
      testing, and determination of mercury concentration in urine. Mercury
      concentration was also measured in the air of working premises of the factory.
      RESULTS: The performed measurements confirmed that the concentrations of mercury
      at any tested working place in the Department of Electrolysis were not more than
      the maximally permitted concentration for an 8-hour exposition. In the exposed
      group (40 examinees) 75% of the examinees had mercury in urine in the
      concentration < 0.1 micromol/l, while in 25% of them it was 0.1-0.75 micromol/l.
      In the control group (20 examinees) all of the examinees showed to have < 0.1
      mol/l mercury in urine. There was determined a positive corelation between the
      concentration of mercury in urine and the value of beta2-microglobulin (p <
      0.05), as well as between the corrcentration of mercury in urine and gammaGT
      activity (p < 0.05), and between the concentration of mercury in urine and the
      value of retinol-binding protein (p < 0.01). CONCLUSION: In 25% of the examinees
      excretion of mercury was significantly higher than in the control group. The
      frequency of asymptomatic renal tubular lesions and dysfunction of moderate
      extent were found to be higher in the exposed group than in the control one.

PMID- 18814503
TI  - [Caries risk estimation in children regarding values of saliva buffer system
      components and carboanhydrase activity].
AB  - BACKGROUND/AIM: One of the preconditions for efficacious systematic reduction of
      caries prevalence and prophylaxis is the determination of risks of this disease
      appearance. The aim of this study was to prove the significance of salivary
      carboanhydrase activity determination in estimation of caries risk in children.
      METHODS: The study included 123 children of average age of 13.4+/-0.3 years and
      permanent dentition. The children were divided into two groups according to
      caries risk (low and high caries risk groups). Two samples of saliva-
      unstimulated and stimulated one were taken from each child. Salivary
      carboanhydrase activity, as well as pH value, bicarbonate and phosphate buffer
      levels were estimated in both group of saliva samples. RESULTS: The investigation
      showed significantly higher carboanhydrase activity (p < 0.001) in both saliva
      samples in low caries risk group compared to high caries risk one. In children
      with low caries risk, both unstimulated and stimulated saliva show significantly
      higher bicarbonate and phosphate buffer concentrations (p < 0.001), as well as pH
      values. CONCLUSION: The lower caries incidence could be expected in children with
      high carboanhydrase activity and higher salivary buffer system parameters levels.
      The presented results suggest that salivary carboanhydrase activity represents
      the important marker of individual susceptibility for caries appearance in
      children.

PMID- 18814504
TI  - [Determination of fibrin glue with antibiotics on collagen production in colon
      anastomosis].
AB  - BACKGROUND/AIM: Fibrin glue is used as a matrix for local application of
      antibiotics. The aim of this study was to determine whether application of fibrin
      glue in combination with antibiotics can strengthen collagen production, prevent
      dehiscence of colon anastomoses due to infection, and reduce frequency of
      mortality and morbidity comparing to the control group and the group with fibrin
      glue application. METHODS: The adult male Wistar rats divided into three groups
      were used in the experiment. The group 1 was the control one (after partial colon
      resection, colonic anastomoses performed were not treated), while to the group 2
      and the group 3 were applied fibrin glue and fibrin glue with antibiotics
      (clindamycin and ceftriaxon) on the site of anastomoses, respectively. Quality of
      colonic anastomoses were estimated by means of determination of collagen (L
      hydroxyproline) amount in the collon wall with anastomoses and histological
      analysis of this colon segment using light and electronic microscope on the days
      5, 7 and 13 postoperatively. RESULTS: The highest morbidity rate was registered
      in the group 1 (30%), then in the group 2 (13.3%) and the lowest one in the group
      3 (3.33%; p < 0.05 vs group 1). Mortality rate was significantly higher in the
      group 1 than in the group 3 (20% and 0%, respectively; p < 0.05). In the
      postoperative course, the highest concentrations of collagen in the colon wall on
      the site of anastomoses, which was confirmed by both light and electronic
      microscopy, were found in the group 3. CONCLUSION: The application of fibrin glue
      with antibiotics on colon anastomoses reduces the number of dehiscence, provides
      good mechanical protection and shorten the time of anastomoses healing.

PMID- 18814505
TI  - [Lung involvement in systemic connective tissue diseases].
AB  - BACKGROUND/AIM: Systemic connective tissue diseases (SCTD) are chronic
      inflammatory autoimmune disorders of unknown cause that can involve different
      organs and systems. Their course and prognosis are different. All of them can,
      more or less, involve the respiratory sistem. The aim of this study was to find
      out the frequency of respiratory simptoms, lung function disorders, radiography
      and high-resolution computerized tomography (HRCT) abnormalities, and their
      correlation with the duration of the disease and the applied treatment. METHODS:
      In 47 non-randomised consecutive patients standard chest radiography, HRCT, and
      lung function tests were done. RESULTS: Hypoxemia was present in nine of the
      patients with respiratory simptoms (20%). In all of them chest radiography was
      normal. In five of these patients lung fibrosis was established using HRCT. Half
      of all the patients with SCTD had simptoms of lung involment. Lung function tests
      disorders of various degrees were found in 40% of the patients. The outcome and
      the degree of lung functin disorders were neither in correlation with the
      duration of SCTD nor with therapy used (p > 0.05 Spearmans Ro). CONCLUSION:
      Pulmonary fibrosis occures in about 10% of the patients with SCTD, and possibly
      not due to the applied treatment regimens. Hypoxemia could be a sing of existing
      pulmonary fibrosis in the absence of disorders on standard chest radiography.

PMID- 18814506
TI  - [Diabetes mellitus--a risk factor for the development of osteoporosis].

PMID- 18814507
TI  - Etiology and pathogenesis of chronic rhinosinusitis.

PMID- 18814508
TI  - [Disseminated subcutaneous fat necrosis and elbow joint arthritis as a
      complication of pancreatitis].
AB  - BACKGROUND: Intraabdominal fat necrosis of the retroperitoneum, mesenthery and
      omentum is a frequent complication of acute pancreatitis. Very rarely, during the
      disease multiple aseptic subcutaneous fat necrosis, polyarthritis, polyserositis,
      vasculitis, subcutaneous nodi and eosinophylia, isolated or in combination, may
      appear. They are known as "pancreatic disease syndrome". CASE REPORT: We
      presented a female patient, 43-year-old, in whom in the course of acute
      interstitial biliary pancreatitis had occur red multiple localized aseptic
      necrosis of subcutaneous fat tissue of extremities appeared mostly around the
      talocrural and wrist joints requiring multiple incision, as well as aseptic elbow
      joints arthritis requiring puncture of one elbow joint. The symptoms were
      followed by a prolonged febrility that settled within several weeks. CONCLUSION:
      Localized disseminated fat necrosis around joints, arthritis of major joints,
      alone or with some of other symptoms of the "pancreatic disease syndrome" have to
      be considered as a probable sign of pancreatitis, even in the abscence of major
      abdominal symptoms.

PMID- 18814509
TI  - [Acute abdomen in a patient with Mayer-Rokitansky-Kuster-Hauser syndrome].
AB  - BACKGROUND: Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome is a malformation of
      female genital tract (incidence 1 in 4000 female newborn children). It appears as
      a result of a disorder in the development of Millerian cannals. Etiology is
      unknown. Syndrome MRKH is the most frequent cause of primary amenorrhoea (90%).
      Patients with MRKH have a normal female phenotype, with normal pubic hairness and
      thelarche, and female karyotype (46XX) followed by primary amenorrhoea. Hormonal
      status corresponds to healthy women, where the appearance of ovarian tumors and
      tumors on rudiment parts of uterus is possible. CASE REPORT: We presented a case
      of acute abdomen in a patient with previously not diagnosed MRKH. The diagnosis
      was done during the operation. Small pelvis and an abdominal part were filled
      with torquated tumor lump, where ovaries, oviducts, uterus or something
      resembling rudiment of uterus were not recognized through careful examination.
      Furthemore, the patient had a short, dead-end vagina. Tumorectomy was done and
      hystopathological finding showed the presence of vascular leiomyoma. CONCLUSION:
      The diagnosis of complex syndromes, such as MRKH, can, despite modern
      diagnostics, be absent for non-medical and psycho-social reasons. We can expect
      ovarian and uterine pathology on hypoplastic structures in these patients, as
      well as in healthy women. Vascular leiomyoma in the patients with MRKH was not
      found in the available literature.

PMID- 18814510
TI  - [Vascular gastric anomalies as a cause of relapsing bleeding].
AB  - BACKGROUND: Although relatively rare, gastric vascular anomalies can be
      recognized as a source of both chronic and acute blood loss, most often
      presenting as long term iron deficiency anemia, rarely as severe acute
      gastrointestinal bleeding. CASE REPORT: We present five patients with various
      gastric vascular anomalies, diagnosed during the year of 2003. in the Clinical
      Hospital Center Zemun. The diagnosis was based on endoscopic appearances,
      clinical history and characteristic histological findings. Gastric vascular
      anomalies presented in our review were: portal hypertensive gastropathy, gastric
      antral vascular ectasia, angiodysplasia, hereditary hemorrhagic telangiectasia
      and Dieulafoy lesion. The used treatment modalities included surgery and various
      endoscopic techniques (schlerotherapy, argon plasma coagulation). CONCLUSION:
      Patients presented with chronic iron deficiency anemia or acute and recurrent
      gastrointestinal hemorrhage should be considered as having one of gastric
      vascular anomalies.

PMID- 18814511
TI  - [Bartolomeo Eustachius--the author of the first published book on dental
      medicine].

PMID- 18814512
TI  - A remark on the clinical experience in treatment of hypertensive patients.

PMID- 18814513
TI  - [Predictable surprise--the 2008 Sichuan earthquake].
AB  - A 7.9 magnitude earthquake struck Sichuan Province of China on Monday, May 12,
      2008. It was a predictable surprise and the most damaging earthquake since the
      2004 Tsunami disaster: over 70,000 dead, about 20,000 missing more than 200,000
      injured and almost ten million homeless. The devastating earthquake was
      accompanied by secondary disasters: multiple aftershocks, mudslides, landslides,
      rock slides, heavy rains, floods, fires, and hazardous source of chemicals and
      radiation. This paper represents search and rescue and medical aspects during the
      first ten days following the earthquake. Specific issues will be discussed such
      as: the secondary disasters, the prompt response of China leaders, the
      inexperience of military to cope with problems related to search and rescue,
      rejection of international assistance maltreatment and poor identification of the
      dead, collapse of the local health system, 'disappearance' of medical and
      paramedical personnel, and poor planning of evacuation routes and shelters. Once
      again we can see that professional first responders and medical personnel tend to
      respond first to their loved ones. The real first responders in the first 24
      hours are always the bystanders, who save more lives than the professionals.

PMID- 18814514
TI  - [Clinical implications and angiographic and electrocardiographic correlation of
      ST segment elevation in leads V7-V9 in patients with ST elevation myocardial
      infarction].
AB  - INTRODUCTION: The clinical significance and clinical characteristics of patients
      with myocardial infarction involving the posterior wall of the left ventricle is
      not well-defined. The angiographic findings and their correlation with the
      eletrocardiographic (ECG) findings may be of high therapeutic importance.
      METHODS: We retrospectively studied consecutive patients with ST elevation
      myocardial infarction on the admission ECG to the intensive cardiac care. We
      studied the clinical and demographic characteristics, the clinical course in
      hospital and the clinical outcome (including infarct size, congestive heart
      failure and significant mitral insufficiency). All patients underwent coronary
      angiography during the index admission. We correlated the ECG findings on
      admission to the angiographic findings. RESULTS: We studied 198 patients with
      mean age of 57 +/- 12 years (range 30-88 years), 158 men (79.8%) and 40 women
      (20.2%). Myocardial infarction involving the inferior wall was noted in 119
      patients, of whom 68 had inferior wall myocardial infarction only, and 51 had
      inferior and lateral wall involvement (leads I, AVL and/or V5-V6). Only 4
      patients (2%) had ST elevation in leads V7-V9 only. The left ventricular ejection
      fraction was lowest in patients with anterior wall myocardial infarction (41% +/-
      6) compared to myocardial infarction with the posterior wall involved (44% +/- 8)
      or myocardial infarction with the inferior wall only (54% +/- 6) (p = 0.023). The
      largest infarct size by peak creatine phosphokinase was found in the
      inferoposterior myocardial infarction group, significantly larger from inferior
      infarction only, and similar to that of anterior myocardial infarction. The
      incidence of congestive heart failure was slightly more in anterior myocardial
      infarction; however, significant mitral valve insufficiency was higher in
      patients with posterior wall involvement, yet with no statistical significance.
      The infarct related artery causing posterior myocardial infarction was
      significantly more frequent in the right coronary artery (57.1%) compared to the
      left circumflex artery (37.5%) (p < 0.01). CONCLUSIONS: The major artery causing
      involvement of the posterior wall is the right coronary artery. In patients with
      myocardial infarction involving the posterior wall, infarct size is similar to
      that of anterior wall myocardial infarction, and with similar complications rate.
      However, the incidence of significant mitral valve insufficiency and congestive
      heart failure is high in patients with posterior wall involvement. Posterior
      leads assessment should be conducted routinely in patients with suspected
      myocardial infarction.

PMID- 18814515
TI  - [Evaluation of ergonomic conditions of video display terminal operators in a
      general hospital].
AB  - Operating a computer terminal is currently an integral part of daily work of both
      administrative and medical personnel in every hospital. Extended work with video
      display terminals (VDTs) is often characterized by typical symptomatology termed
      as cumulative trauma disorders (CTD) or repetitive strain injuries (RSI). We have
      demonstrated that about 80% of the hospital VDT operators had complaints
      compatible with CTD/RSI and 16% were treated for these conditions. These findings
      indicate the need to incorporate ergonomists in planning or modifying current VDT
      work stations in order to minimize the development of such symptoms.

PMID- 18814516
TI  - [Prostatic abscess--diagnosis and treatment].
AB  - Prostatic abscess is an uncommon condition, often difficult to discern clinically
      from acute prostatitis. It results from focal accumulation of pus within the
      prostate gland. Historically, the common infecting organisms were Neisseria
      gonorrheae, Staphylococcus aureus and Mycobacterium tuberculosis. However, more
      recently, gram negative bacteria, such as Escherichia coli, are causative
      species. Prostatic abscess mainly affects diabetic and immunosuppressed patients.
      In the past, transurethral drainage was the first choice for therapy. Today,
      percutaneous transperineal or transrectal drainage under transrectal sonography
      is the first choice for therapy because of the low risk of complication. This is
      a case history of 47-year old male patient who was admitted due to prostatic
      abscess. On admission he complained of severe dysuria and high fever lasting 10
      days after antibiotic treatment for urinary tract infection. On rectal
      examination the prostate was enlarged and very tender. Both the CT-scan and
      transrectal ultrasound revealed well defined fluid collection areas compatible
      with an abscess in the right lobe of the prostate. Under general anesthesia and
      transrectal ultrasound guidance the abscess was aspirated transperineally. A 12-F
      drain was left for 6 days with complete remission in clinical and CT findings.
      Once an abscess of the prostate is diagnosed, anaerobic antimicrobial therapy
      should be added and transrectal or percutaneous transperineal aspiration and
      drainage is required. The authors consider the percutaneuos transperineal
      drainage to be the most effective and safest solution.

PMID- 18814517
TI  - [Ethiopia in Israel--an ethnopharmacological study of Ethiopian immigrants in
      Israel].
AB  - There is a large Ethiopian community in Israel which preserves its unique culture
      and customs. Many of the members of this community still use traditional methods
      of healing, such as blood-letting, burns, tattooing, amulets, healing water,
      incense and various medicinal herbs that are prescribed based on the diagnosis of
      the disease. This study deals with documenting the use of the medicinal drugs
      implemented by the Ethiopian community in Israel, which is a rapidly vanishing
      world. The study is based on interviews with hundreds of informants, among them
      traditional healers, and it surveyed some fifty shops which sell Ethiopian
      medicinal drugs and spices. The survey brought to light a list of medical
      materials which are found in the Ethiopian markets in Israel including 89 kinds
      of plants (some 85%); 6 different minerals (some 6%); 5 types of animals (some
      4.5%); and 5 substances of various origins (some 4.5%). Most of the drugs are
      imported from Ethiopia to Israel, since they are endemic. There are also other
      medicinal drugs that are gathered in the field in Israel or brought through
      personal import; in total, our estimate is that there are approximately 150
      different kinds of medicinal drugs in use in Israel. This is a relatively small
      number when compared to the inventory of drugs in the land of origin, Ethiopia.
      The decline in the use of traditional drugs, due to limited availability and
      processes of modernization in the Ethiopian community in Israel, heightens the
      importance of a study that documents this unique culture. The study is also of
      assistance to the modern medical authorities in order to better understand and
      become more familiar with the Ethiopian community and with its needs and special
      practices, in terms of both prevention and treatment.

PMID- 18814518
TI  - [Referral letters to the pediatric emergency department].
AB  - Referral letters to pediatric emergency departments (ED) may be an important
      source of information available to the emergency department staff. This mode of
      communication has been subject to relatively few studies. OBJECTIVES: Our
      objective was to canvass the expectations of ED physicians from referral letters
      and contrast these expectations with the actual content of referral letters.
      METHODS: A questionnaire containing different items of information that may
      appear in referral letters was distributed to ED pediatricians. The physicians
      scored these items and were asked to add other items that should, in their
      opinion, appear in referral letters. Scores given to the items ranged from "not
      important" (score = 1) to "very important" (score = 5). Information regarding the
      physician's experience in the field of pediatrics was obtained. Subsequently,
      sequential referral letters were collected from a pediatric ER. These letters
      were analyzed with respect to the items scored in the first part of the study.
      Letters were stratified to handwritten and form letters, and by language.
      RESULTS: A total of 21 physicians participated in the study. The mostly valued
      pieces of information were clinical information (principal complaint, physical
      examination prior to referral, past medical history) as well as demographic data
      and information regarding the referring physician. Lower scores were given to
      items regarding socioeconomic background of the patient, immunizations and
      tentative diagnosis. A total of 299 letters were collected. Items missing in more
      than 50 percent of letters were: socioeconomic background, family medical
      history, allergies, immunizations, current medications, referring physician's
      phone number, past medical history. Form letters contained more information than
      handwritten letters. CONCLUSION: Referral letters to pediatric ED's do not live
      up to the expectations of the receiving physicians. Specific expectations from,
      and shortcomings of letters may be pinpointed and addressed.

PMID- 18814519
TI  - [Lucentis versus Avastin--is there a light at the end of the tunnel for age
      related macular degeneration patients?].
AB  - Age-related macular degeneration is the leading cause of blindness and visual
      impairment in the developed world. The recently introduced anti-vascular
      endothelial growth factor (VEGF) intravitreal injections of Ranibizumab
      (Lucentis) and Bevacizumab (Avastin) generated a heated academic argument: on the
      one hand Lucentis is the only drug that was proven effective and relatively safe
      in large prospective double-blinded studies, albeit this drug is expensive and
      might cost up to $1000 per single injection. On the other hand, Avastin is widely
      used worldwide as a low cost alternative for Lucentis, with an estimated cost of
      about $120 per injection, although its efficacy and side effects were
      investigated only in smaller retrospective studies. The ophthalmic community
      still lacks definite information regarding which is the preferred drug, and
      awaits the results of a large prospective study comparing the two drugs.

PMID- 18814520
TI  - [Sick building syndrome].
AB  - Over the past 50 years, a new man-made ecosystem has developed--the controlled
      indoor environment within the sealed exterior shells of modern non-industrial
      buildings. Emitted toxic volatile compounds from building materials, furnishings,
      and equipment, and inappropriate ventilation (resulting from the need to reduce
      expenses) contribute to reduce indoor air quality (IAQ), which has considerable
      potential to affect public health. Consequently, health problems related to this
      ecosystem have emerged. "Building-related illnesses" (BRI) refers to a group of
      illnesses with a fairly homogeneous clinical picture, objective abnormalities on
      clinical or laboratory evaluation, and one or more identifiable sources or agents
      known to cause infectious, immunologic, or allergic diseases. The term "sick
      building syndrome" (SBS) is used to refer to a heterogeneous group of work
      related symptoms--including irritation of the skin and mucous membranes of the
      eyes, nose, and throat, headache, fatigue, and difficulty concentrating. These
      are considered illnesses because of the occurrence of symptoms, even though
      affected workers do not have objective clinical or laboratory abnormalities and
      causative agents cannot be found. The clinical symptoms of SBS, although not life
      threatening are disruptive: they reduce productivity and increase absenteeism
      from work. Noteworthy, the association of symptoms with psychosocial factors does
      not mean that "the problem is all in the workers' heads". The results of
      psychological testing of symptomatic and asymptomatic office workers are similar.
      To improve IAQ and reduce symptoms of SBS adequate ventilation and fresh air,
      which will reduce volatile compounds, maintaining thermal comfort (with humidity
      not exceeding 60%), and adequate lighting should be ensured.

PMID- 18814521
TI  - [Pre-participation screening of individuals engaging in noncompetitive physical
      activity].
AB  - There is accumulating data suggesting that physical activity is associated with
      reduced total mortality, sudden cardiac death, reduced risk of cardiovascular
      diseases, colon and breast cancer, osteoporosis, diabetes, hypertension, obesity,
      cognitive decline, dementia and depression. In addition, physical activity
      increases work productivity and well-being. Despite these health benefits, only
      approximately 30% of Israelis engage in regular physical activity. In Israel, the
      Physical Fitness Law requires a medical clearance prior to participation in
      physical activity in the gym. However, the medical community does not have
      written recommendations as to what type of examinations one should undergo. This
      paper was written following a request by the National Committee for the
      Prevention and Treatment of Cardiovascular Diseases, Israeli Ministry of Health,
      joined by the Israeli Heart Society to write new recommendations for the primary
      health care physician on the medical screening needed prior to the participation
      in a non-competitive physical activity among healthy Israelis. It includes a self
      report physical activity readiness questionnaire (PAR-Q), medical examinations,
      and exercise stress test. Since moderate types of physical activity performed
      under supervised conditions in a health/fitness facilities are safe, the
      recommendations for most individuals would be to complete the PAR-Q questionnaire
      with no further medical examinations. The position of the authors in the current
      article is similar to that approved by the National Committee for the Prevention
      and Treatment of Cardiovascular Diseases and the Israeli Heart Society and as was
      published by the Israel Medical Association.

PMID- 18814522
TI  - [Osteochondritis dissecans of the knee].
AB  - Osteochondritis dissecans of the knee is diagnosed at an increasing rate among
      adolescents and young adults. One of the reasons is due to the increasing number
      of sports participants among these populations. Although many theories exist, the
      cause of osteochondritis dissecans is unknown. Early diagnosis is very important.
      While adult type osteochondritis dissecans is unstable, in most young patients it
      is stable, and patients with an intact articular surface have a good chance to
      heal with non-operative treatment and cessation of physical activity. The value
      of complementary treatment (bed rest, partial weight bearing, bracing aimed at
      reducing weight bearing of the involved knee) is unknown. Patients with open
      physes and stable lesions, who failed non-operative treatment, may be treated
      with local bone drilling, encouraging lesion healing. As the disease progresses,
      more aggressive measures should to be taken, whilst decreasing success ratios are
      expected. The healing potential of the lesion may be evaluated by magnetic
      resonance imaging. Most adult type osteochondritis dissecans patients, as most
      young patients, with unstable lesions and loose bodies within their knees, are
      treated with fixation of the lesions and even bone grafting. Many unstable
      lesions will heal after fixation, but the long-term prognosis is elusive. Chronic
      loose bodies are very difficult to fix, with less favorable outcomes. Excision of
      large lesions originating from weight bearing cartilage is not favorable and
      different rehabilitation measures of local cartilage damage are not encouraging.

PMID- 18814523
TI  - [Cancer-related lymphedema in Israel].
AB  - Lymphedema, the accumulation of protein-rich fluid in an involved extremity or
      other body part, is a chronic life-long condition following many types of
      surgical procedures, most often breast cancer surgical therapy. The patient
      suffering from lymphedema faces difficult medical, social, psychological and
      aesthetic issues. The incidence of lymphedema after modern breast cancer surgical
      treatment has been reported for between 5 to 56% of patients. Taking into account
      the incidence of breast cancer in Israel, there could be a yearly incidence of
      over 1000 new patients per year in Israel suffering from arm lymphedema. The
      authors reviewed the literature concerning epidemiology, pathophysiology, risk
      factors, diagnosis and treatment strategy. In addition, some insights were
      provided regarding lymphedema treatment in Israel. This review aims to improve
      the awareness and knowledge of physicians and other health care professionals on
      this treatable but often forgotten condition.

PMID- 18814524
TI  - [Anxiety disorders in children and adolescents].
AB  - Anxiety disorders are the most common psychiatric illnesses in children and
      adolescents. They are associated with significant distress and impairment. Most
      of the children and adolescents with anxiety disorders are not detected and only
      a minority receives adequate treatment. Anxious children and adolescents often
      follow a chronic course of disease with elevated risk of depressive disorders,
      substance abuse and even suicide. Risk factors for anxiety disorders are complex
      and consist of intricate interplay of multiple factors, including genetic makeup
      and environmental risks. Effective, evidence-based treatments for anxiety
      disorders in children and adolescents consist of cognitive-behavioral therapy and
      pharmacotherapy with serotonin specific reuptake inhibitors. Further research is
      needed to design high-quality screening tools for anxiety disorders in the
      primary care setting.

PMID- 18814525
TI  - ["Injecting clean or being clean?" The international and Israeli experiences of
      Syringe Exchange Programs among injecting drug users].
AB  - Injecting drug users (IDU) are a hard-to-reach population. The treatment
      objectives are to reduce their risk factors, to guide them to total abstinence or
      to antagonist treatment. When IDU are not ready for detoxification, they are
      referred to Syringe Exchange Programs (SEP). The objective of SEP is harm
      reduction of blood-borne viruses (of HIV, HBV, HCV). The authors aimed to define
      the issues related to harm reduction, to discuss the results of SEP in the world,
      and to describe our experience. We analyzed the world literature and our
      experience. In this article, we describe the rehabilitation school of thought
      (which supports complete drug abstinence), the harm reduction school of thought
      (which refers to drug addiction as a chronic disease), and the possible continuum
      between these two schools of thought. The AIDS pandemic and the epidemiology of
      world drug addiction by injection are described, together with the principles of
      SEP and their evaluation in the world. In addition, we describe drug use in
      Israel and HIV infection among IDU. Finally, we analyze our preliminary results
      of the SEP pilot in Israel, during the years 2004-2005, and included 462 IDUs. In
      conclusion, considering the difficulties that exist with IDUs, most articles
      emphasize the importance of SEP in this population while sometimes also
      expressing its effectiveness in preventing transmissions of blood-borne viruses.
      In Israel, a pilot project has existed since the end of 2003, and has expanded
      progressively to three cities. An overall evaluation of this program is under
      preparation.

PMID- 18814526
TI  - [Radical prostatectomy--100 years of evolution].
AB  - Prostate cancer is the most common malignant disease in men. The incidence of
      prostate cancer has been rising since the early 1990s. Not all men inflicted by
      prostate cancer will develop clinical disease. Therefore, sorting these cases is
      a great clinical challenge. Radical prostatectomy has undergone evolution in the
      last 100 years. Better understanding of the pelvic anatomy has led to a decrease
      in the blood loss during surgery and in the rate of urinary incontinence and
      erectile dysfunction following surgery. The introduction of laparoscopy in the
      late 1990s to this surgery provided the surgeon with a magnified multi-angle
      field of view and facilitated accurate dissection and suturing. Decreased damage
      to neighboring tissue made recovery hastier. Nevertheless, laparoscopic radical
      prostatectomy is a technically challenging surgery and did not become popular.
      The last step in the evolution of radical prostatectomy is the introduction of
      robotic systems for assistance in laparoscopic radical prostatectomy. A master
      slave robotic system is composed of console and mechanical arms. The surgeon is
      provided with a magnified three dimensional view of the operative field and with
      two mechanical arms that accurately replicate its fingers movements. The initial
      results of robotic-assisted laparoscopic prostatectomy seem promising, however,
      long-term follow-up and comparison to open surgeries are lacking. Robotic systems
      were rapidly implemented in the American market and in the year 2006, 40% of all
      radical prostatectomies were robotic assisted. Future systems may reveal deep
      structures to the visualized surface by superimposing MRI images on the surgical
      field.

PMID- 18814527
TI  - [The crucial encounter between technology and medicine].
AB  - The technological revolution has characterized the past fifty years of medical
      care. Innovations in health services have dramatically improved patients' quality
      of life and longevity while reducing the rate of hospitalization and enhancing
      productivity. Nevertheless, it is clear that modern technological advances both
      represent and claim a large portion of current health expenditures. This article
      presents an historical review of the advances in health services in the USA and
      Israel, and the unique contribution of medical technology (MT) in determining the
      supply and demand in the health systems. It will outline the factors that
      influence the processes of health technology assessment and decision-making in
      allocating the appropriate utilization of MT in an era of limited resources.

PMID- 18814528
TI  - [The elderly and access to the intensive care unit: the battle for the last bed].

PMID- 18814529
TI  - Burkitt's lymphoma-- what is new?

PMID- 18814530
TI  - Burkitt's lymphoma in Uganda: the role of immunohistochemistry in diagnosis.
AB  - BACKGROUND: Haematoxylin and eosin staining has remained the standard diagnostic
      method for Burkitt's lymphoma. Ancillary tests including immunohistochemistry,
      not widely available in developing countries, are important tools in verifying
      the diagnosis of lymphomas with equivocal morphological findings. OBJECTIVE: To
      evaluate the reliability of haematoxylin and eosin staining in the diagnosis of
      Burkitt's lymphoma using immunohistochemistry as the gold standard. DESIGN: Cross
      sectional study. SETTING: Department of Pathology laboratory, Makerere University
      Medical School, Uganda. SUBJECTS: One hundred and thirty eight formalin fixed
      paraffin embedded biopsies of Burkitt's lymphoma diagnosed from January 2001 to
      December 2005. RESULTS: Of the 138 tumours, 88.4% were extra-nodal: jaw 36.2%,
      ovary 21%, gastrointestinal tract 12.3% other abdominal 11.6%. Males (55.8%)
      predominated. The sensitivity and specificity of haematoxylin and eosin were
      93.2% and 50% respectively. The positive and negative predictive values were
      91.7% and 55.6%. CONCLUSION: Histology using haematoxylin and eosin staining is
      sensitive in the diagnosis of Burkitt's lymphoma but not very specific.
      Immunohistochemical staining with CD20, Ki-67 and bcl-2 is necessary for
      difficult cases.

PMID- 18814531
TI  - Health facility and health worker readiness to deliver new national treatment
      policy for malaria in Kenya.
AB  - OBJECTIVE: To evaluate health facility and health worker readiness to deliver new
      artemether-lumefantrine (AL) treatment policy for uncomplicated malaria in Kenya.
      DESIGN: Cross-sectional survey. SETTING: Health facilities in four sentinel
      districts in Kenya. PARTICIPANTS: All government facilities in study districts (n
      = 211) and all health workers performing outpatient consultations (n = 654). MAIN
      OUTCOME MEASURES: Availability of antimalarial drugs on the survey day, stock
      outs in past six months, presence of AL wall charts, health worker's exposure to
      in-service training on AL and access to new national malaria guidelines. RESULTS:
      The availability of any tablets of AL, sulfadoxine-pyrimethamine and amodiaquine
      was nearly universal on the survey day. However, only 61% of facilities stocked
      all four weight-specific packs of AL. In the past six months, 67% of facilities
      had stock-out of at least one AL tablet pack and 15% were out of stock for all
      four packs at the same time. Duration of stock-out was substantial for all AL
      packs (median range: 27-39% of time). During the same period, the stock-outs of
      sulfadoxine-pyrimethamine and amodiaquine were rare. Only 19% of facilities had
      all AL wall charts displayed, AL in-service training was provided to 47% of
      health workers and 59% had access to the new guidelines. CONCLUSION: Health
      facility and health worker readiness to implement AL policy is not yet optimal.
      Continuous supply of all four AL pack sizes and removal of not recommended
      antimalarials is needed. Further coordinated efforts through the routine
      programmatic activities are necessary to improve delivery of AL at the point of
      care.

PMID- 18814532
TI  - Polio outbreak response in Ethiopia.
AB  - BACKGROUND: Ethiopia had been polio-free for almost four years until December
      2004. However, between December 2004 and February 2006, 24 children were
      paralysed as a result of infection with wild poliovirus imported from the
      neighbouring country of Sudan. In response, the country has attempted to document
      the impact of various response measures on the containment of wild poliovirus
      transmission. OBJECTIVES: This study aims at systematic and epidemiological
      assessment of the extent of the outbreak, its determinants, and the lessons
      learned as well as the implications for future control strategies to interrupt
      wild poliovirus transmission. DESIGN: A cross-sectional study design with
      qualitative and quantitative data collection approaches was used to conduct the
      epidemiologic assessment. SUBJECTS: All confirmed wild poliovirus cases, and
      reported acute flaccid paralysis cases in close proximity to the confirmed polio
      cases were the study subjects. Child caretakers and health service providers were
      interviewed as part of the investigation. RESULTS: Between December 2004 and
      February 2006, eight children from Tigray Regional State, nine children from
      Amhara Regional State and seven children from Oromia Regional State were
      paralysed as a result of infection with wild poliovirus type 1. Genetic
      sequencing demonstrated two separate importations to Ethiopia. Risk factors that
      may have facilitated spread of the outbreak within the country included gaps in
      vaccination coverage and interruption of the cold chain system, gaps in acute
      flaccid paralysis surveillance performance, high population mobility, poor
      environmental sanitation, crowded living conditions and unsafe drinking water. In
      response to the outbreak, Ethiopia conducted detailed outbreak investigations
      within two days of confirmation of the index cases. Large-scale, house-to-house
      vaccination campaigns were also implemented. As a result, the three regions
      interrupted the wild poliovirus transmission within the regions within one year
      of confirmation of the index case. CONCLUSION: Outbreak response activities were
      successful in interrupting the imported wild poliovirus transmission in Tigray,
      Amhara and Oromia Regional States of Ethiopia within a one-year period of time.
      In Ethiopia, programme strategies should be intensified to contain further spread
      and prevent future importation of wild poliovirus. Large-scale immunisation
      campaigns should reach every child, including those isolated by geography,
      poverty and security.

PMID- 18814533
TI  - Workload Indicators of Staffing Need method in determining optimal staffing
      levels at Moi Teaching and Referral Hospital.
AB  - BACKGROUND: There is an increasing demand for quality healthcare in the face of
      limited resources. With the health personnel consuming up to three quarters of
      recurrent budgets, a need arises to ascertain that a workforce for any health
      facility is the optimal level needed to produce the desired product. OBJECTIVE:
      To highlight the experience and findings of an attempt at establishing the
      optimal staffing levels for a tertiary health institution using the Workload
      Indicators of Staffing Need (WISN) method popularised by the World Health
      Organisation (WHO), Geneva, Switzerland. DESIGN: A descriptive study that
      captures the activities of a taskforce appointed to establish optimal staffing
      levels. SETTING: Moi Teaching and Referral Hospital (MTRH), Eldoret, Kenya, a
      tertiary hospital in the Rift Valley province of Kenya from September 2005 to May
      2006. MAIN OUTCOME MEASURES: The cadres of workers, working schedules, main
      activities, time taken to accomplish the activities, available working hours,
      category and individual allowances, annual workloads from the previous year's
      statistics and optimal departmental establishment of workers. RESULTS: There was
      initial resentment to the exercise because of the notion that it was aimed at
      retrenching workers. The team was given autonomy by the hospital management to
      objectively establish the optimal staffing levels. Very few departments were
      optimally established with the majority either under or over staffed. There were
      intradepartmental discrepancies in optimal levels of cadres even though many of
      them had the right number of total workforce. CONCLUSION: The WISN method is a
      very objective way of establishing staffing levels but requires a dedicated team
      with adequate expertise to make the raw data meaningful for calculations.

PMID- 18814534
TI  - Factors influencing the use of episiotomy during vaginal delivery in South
      Eastern Nigeria.
AB  - BACKGROUND: Given considerable evidence that routine episiotomy increases
      maternal morbidity and without evidence to support maternal or neonatal benefit,
      has episiotomy use changed among health care providers? To date, very limited
      information exists relating to the past and current practice of episiotomy in
      many developing countries. OBJECTIVE: To determine the prevalence of episiotomy
      at Aba in South Eastern Nigeria, examine factors influencing the performance of
      episiotomy and document complications associated with the procedure. DESIGN: A
      hospital based retrospective study. SETTING: The Abia State University Teaching
      Hospital (ABSUTH), Aba in South Eastern Nigeria, from January 2001 to December
      2005. SUBJECTS: Four thousand, one hundred and seventy two mothers who delivered
      vaginally within the study period. RESULTS: There were 1877 episiotomies, for an
      episiotomy rate of 45%. Ninety per cent of the primigravid parturients had
      episiotomy. Women undergoing episiotomy were younger (mean age 24.7 years; range
      16-37) than women without episiotomy (mean age 28.5 years, range 20-43). When
      controlled for parity and maternal age, other risk factors were occipito
      posterior position, vacuum extraction, forceps delivery, vaginal breech delivery,
      and a history of Caesarean section. Episiotomy use was also associated with major
      perineal lacerations and increased length of hospital stay. CONCLUSION: The
      episiotomy rate of 45 per 100 vaginal deliveries in this study is obviously
      higher than evidence-based recommendations for optimal patient care. A policy of
      systematic reduction in the incidence of episiotomy can be pursued in this
      hospital. Greater attention needs to be paid to selection of women to undergo
      episiotomy.

PMID- 18814535
TI  - Anatomical variations of the carotid arteries in adult Kenyans.
AB  - OBJECTIVE: To describe the topography and anatomical variations of the carotid
      arteries among Kenyans. DESIGN: A descriptive cross-sectional study. SETTING:
      Department of Human Anatomy, University of Nairobi. SUBJECTS: Eighty carotid
      arteries of forty cadavers were dissected. RESULTS: The bifurcation of the
      commonest carotid artery was high (above the reference points) in 63.8% of
      vessels and the external carotid was antero-lateral to the internal carotid
      artery in 30% of the vessels. A linguo-facial trunk was the most common variation
      of the external carotid artery. The origin of the right common carotid artery was
      high and low in 10% and 2.6% of vessels respectively. CONCLUSION: The carotid
      arteries show important variability and thus emphasise caution for clinicians
      during surgical procedures in the neck.

PMID- 18814536
TI  - Unusual presentation of idiopathic retroperitoneal fibrosis: case report.
AB  - Idiopathic retroperitoneal fibrosis (IRF) is an uncommon entity described as
      progressive proliferation of connective tissues leading to a fibrous plaque-like
      lesions that encases the aorta and inferior vena cava inferior to the level of
      the renal arteries. Mass forming retroperitoneal fibrosis is rare. We present a
      rare case of a unilateral focal retroperitoneal mass simulating a tumour encasing
      the middle third of the left ureter, with involvement of the ipsilateral scrotum.

PMID- 18814537
TI  - Therapeutic non-disclosure of adverse health information to an obstetric patient:
      case report.
AB  - The non-disclosure of foetal exomphalos discovered on intra-uterine ultrasound to
      the mother and anaesthesiologist in this case report, was based on the
      obstetricians' assumption that it will reduce maternal stress in the antenatal
      period. There was mis-information that all was well in the antenatal period in
      spite of maternal informed consent. However, it led to maternal stress and
      dissatisfaction with the physician. The patient was referred to the psychiatrist
      for management of her stressful encounter in the postoperative period. Ethical
      and medico-legal issues raised by therapeutic non disclosure of health
      information to the patient beforehand was addressed and physician knowledge
      updated by a review of current literature on the subject.

PMID- 18814538
TI  - Big orthopedic settlement could swing pricing pendulum toward hospitals.

PMID- 18814539
TI  - Supply chain exec pay higher in GPOs than hospitals. GPO-based execs report
      earning 3.3% more in 2008 salary survey.

PMID- 18814540
TI  - Little back pain: key spinal product prices remain steady while spine surgeries
      continue upward path. Increased use of BMP, not internal fixation products,
      pushes hospital budgets.

PMID- 18814541
TI  - Sterile processing comes out clean as complement to successful materials
      management. How Cedars-Sinai used a Lean strategy to help build materials-sterile
      processing teamwork.

PMID- 18814542
TI  - Characterization of Renibacterium salmoninarum with reduced susceptibility to
      macrolide antibiotics by a standardized antibiotic susceptibility test.
AB  - Three cohorts of juvenile and subadult Chinook salmon Oncorhynchus tshawytscha
      received multiple treatments with macrolide antibiotics for bacterial kidney
      disease (BKD) during rearing in a captive broodstock program. A total of 77
      mortalities among the cohorts were screened for Renibacterium salmoninarum, the
      etiologic agent of BKD, by agar culture from kidney, and isolates from 7 fish
      were suitable for growth testing in the presence of macrolide antibiotics. The
      minimum inhibitory concentration (MIC) of erythromycin and azithromycin was
      determined by a modification of the standardized broth assay using defined
      medium. The American Type Culture Collection (ATCC) type strain 33209 exhibited a
      MIC of 0.008 microg m(-1) to either erythromycin or azithromycin. Isolates from 3
      fish displayed MICs identical to the MICs for the ATCC type strain 33209. In
      contrast, isolates from 4 fish exhibited higher MICs, ranging between 0.125 and
      0.250 microg ml(-1) for erythromycin and between 0.016 and 0.031 microg ml(-1)
      for azithromycin. Sequence analysis of the mutational hotspots for macrolide
      resistance in the 23S rDNA gene and the open reading frames of ribosomal proteins
      L4 and L22 found identical sequences among all isolates, indicating that the
      phenotype was not due to mutations associated with the drug-binding site of 23S
      rRNA. These results are the first report of R. salmoninarum with reduced
      susceptibility to macrolide antibiotics isolated from fish receiving multiple
      antibiotic treatments.

PMID- 18814543
TI  - Portal of entry for pathogenic Vibrio alginolyticus into large yellow croaker
      Pseudosciaena crocea, and characteristics of bacterial adhesion to mucus.
AB  - The portal of entry for pathogenic Vibrio alginolyticus into large yellow croaker
      Pseudosciaena crocea is via the intestinal tract rather than gill or skin
      according to the kinetics of the bacterial adhesion to different mucus. The
      different effects on adhesion caused by proteolytic enzymes and heat treatment
      might be due to the different chemical compositions of mucus. Adhesion of V.
      alginolyticus to mucus depends on concerted action of bacterial surface
      structures such as cell-surface proteins, somatic antigens, flagella, etc. In
      addition, starvation and monosaccharides, especially fructose, inhibit the
      bacterial adhesion to the mucus. Knowledge of these adhesive characteristics
      should be very useful for designing more efficacious prophylactic strategies.

PMID- 18814544
TI  - Immune-relevant genes expressed in rainbow trout following immunisation with a
      live vaccine against Ichthyophthirius multifiliis.
AB  - Rainbow trout Oncorhynchus mykiss were immunised by intra-peritoneal injection
      using a live vaccine based on Ichthyophthirius multifiliis (Ich) theronts, which
      previously has shown protection against white spot disease. Samples were taken
      pre-vaccination and on Day 1, 7, 21 and 28 post-immunisation (p.i.). Expression
      of immune relevant genes in the liver, spleen and head kidney was monitored by
      qPCR. To describe the immune reaction following this immunisation, a series of
      genes encoding cytokines, complement factors, immunoglobulins and acute phase
      reactants were studied. Genes encoding acute phase reactants in the liver were up
      regulated with serum amyloid A (SAA) as the most pronounced with a 2299-fold
      increase at 24 h p.i. Hepcidin and pre-cerebellin were also up-regulated in the
      liver 24 h p.i., by 7- and 4-fold, respectively. Complement factors C3, C5 and
      factor B (Bf) were up-regulated in the spleen and the head kidney 24 h and 28 d
      p.i. Genes encoding immunoglobulins were not up-regulated, but a specific low
      titer IgM response (titer 25) against parasite antigens was detected by a
      modified ELISA 4 wk p.i.

PMID- 18814545
TI  - Myxidium scripta n. sp. identified in urinary and biliary tract of Louisiana
      farmed red-eared slider turtles Trachemys scripta elegans.
AB  - During a necropsy investigation of a mortality event occurring at a turtle farm
      in Assumption Parish, Louisiana, spores of a myxozoan were identified in the
      renal tubules in 3 of 6, the gall bladder lumen in 2 of 6, and the bile ductule
      in 1 of 6 red eared slider turtles Trachemys scripta elegans. In total, myxozoa
      were identified in 4 of 6 turtles. In 1 turtle, renal tubules contained numerous
      mature spores, had epithelial hyperplasia, granulomatous transformation,
      compression of adjacent tubules and interstitial lymphocytic nephritis. The genus
      of myxozoan was Myxidium, based on spore morphology in cytological preparations,
      in histologic section, and by electron microscopy. In cytological preparation the
      spores had mean dimensions of 18.8 x 5.1 microm and a mean polar capsule
      dimension of 6.6 x 3.5 microm. Electron microscopy showed renal tubules contained
      plasmodia with disporoblasts with spores in various stages of maturation.
      Ultrastructure of mature spores demonstrated a capsule containing 2 asymmetrical
      overlapping valves and polar capsules containing a polar filament coiled 6 to 8
      times and surrounded by a membrane composed of a double layer wall. The small
      subunit rDNA gene sequence was distinct from all other Myxidium species for which
      sequences are available. Additionally, this is the first Myxidium species
      recovered from a North American chelonian to receive genetic analysis. Although
      T. s. elegans is listed as a host for Myxidium chelonarum, this newly described
      species of Myxidium possessed larger spores with tapered ends; thus, we described
      it as a new species, Myxidium scripta n. sp. This report documents a clinically
      significant nephropathy and genetic sequence from a Myxidium parasite affecting a
      freshwater turtle species in North America.

PMID- 18814546
TI  - Marine killer yeasts active against a yeast strain pathogenic to crab Portunus
      trituberculatus.
AB  - Some marine yeasts have recently been recognised as pathogenic agents in crab
      mariculture, but may be inhibited or killed by 'killer' yeast strains. We
      screened multiple yeast strains from seawater, sediments, mud of salterns, guts
      of marine fish, and marine algae for killer activity against the yeast
      Metchnikowia bicuspidata WCY (pathogenic to crab Portunus trituberculatus), and
      found 17 strains which could secrete toxin onto the medium and kill the
      pathogenic yeast. Of these, 5 strains had significantly higher killing activity
      than the others; routine identification and molecular methods showed that these
      were Williopsis saturnus WC91-2, Pichia guilliermondii GZ1, Pichia anomala YF07b,
      Debaryomyces hansenii hcx-1 and Aureobasidium pullulans HN2.3. We found that the
      optimal conditions for killer toxin production and action of killer toxin
      produced by the marine killer yeasts were not all in agreement with those of
      marine environments and for crab cultivation. We found that the killer toxins
      produced by the killer yeast strains could kill other yeasts in addition to the
      pathogenic yeast, and NaCl concentration in the medium could change killing
      activity spectra. All the crude killer toxins produced could hydrolyze laminarin
      and the hydrolysis end products were monosaccharides.

PMID- 18814547
TI  - Brown muscle disease (BMD), an emergent pathology affecting Manila clam Ruditapes
      philippinarum in Arcachon Bay (SW France).
AB  - We describe an emerging pathology, brown muscle disease (BMD), which specifically
      affects the Manila clam Ruditapes philippinarum in Arcachon Bay (France). BMD
      induces a transformation of the posterior adductor muscle, which becomes infused
      by conchiolin and calcified, reducing the ability of clams to bury. The disease
      affects both types of muscular tissue, with striated muscle becoming affected to
      a higher degree than smooth muscle. Two indices were created to quantify the
      symptoms: the Muscle Print Index, used for empty and live shells, and the Final
      Disease Index, utilized for live clams only. Histological sections were made and
      observed under light microscopy to examine the muscular damage and to investigate
      a causal agent. Sections revealed an important inflammatory response with a large
      invasion of hemocytes into tissues and a heavy necrosis of muscular fibers.
      Additionally, molecular biology analyses were carried out to search for bacteria
      and protozoan agents using generic primers. In both histological and molecular
      assays, bacteria and protozoans were discounted. We monitored 4 sites scattered
      around the bay over 2 yr. The mean prevalence was <12% without seasonal variation
      in 3 sites against 30% and a winter peak in 1 site. The latter site was
      accurately surveyed and revealed that clams at the sediment surface (abnormal
      position) were affected 3 times more frequently than buried clams (normal
      position).

PMID- 18814548
TI  - First isolation of Nocardia crassostreae from Pacific oyster Crassostrea gigas in
      Europe.
AB  - In summer 2006 an extensive mortality of Pacific oysters Crassostrea gigas
      occurred in Lake Grevelingen, the Netherlands. A sample of Pacific oysters was
      investigated for the presence of shellfish pathogens as potential causes of the
      mortality. Yellow-green lesions were observed in several oysters upon clinical
      inspection. Histopathology showed that 6 out of 36 oysters had a suspected
      bacterial infection, including 4 Nocardia-like infections. Two bacterial species,
      Vibrio aestuarianus and Nocardia crassostreae, were isolated from haemolymph
      samples and identified using PCR and sequencing of the 16S rRNA gene. This is the
      first isolation of N. crassostreae from shellfish in European waters. The near
      full-length 16S rRNA sequence of this Dutch Nocardia sp. isolate was identical to
      other known N. crassostreae isolates from the west coast of North America. The
      primary cause of oyster mortality was thought to be the physiological stress from
      environmental conditions, including prolonged high water temperatures and low
      oxygen levels. The multiple bacterial species isolated from the diseased Pacific
      oysters may have been a secondary cause.

PMID- 18814549
TI  - Shellfish tissues evaluated for Perkinsus spp. using the Ray's fluid
      thioglycollate medium culture assay can be used for downstream molecular assays.
AB  - Ray's fluid thioglycollate medium (RFTM) culture assay is the standard,
      recommended method for surveillance of Perkinsus spp. infections in marine
      molluscs. In this assay, shellfish tissues are incubated in RFTM, stained with
      Lugol's iodine solution to render Perkinsus spp. cells blue-black, and evaluated
      microscopically to rate infection intensities. A limitation of this assay,
      however, is the lack of pathogen species specificity. Generally, identification
      of Perkinsus spp. requires DNA sequence analysis of parallel or additional
      samples since the exposure to iodine is believed to hamper DNA amplification from
      samples processed by the RFTM assay. However, we show that P. marinus DNA can be
      successfully amplified by PCR from Crassostrea virginica tissues cultured in RFTM
      and stained with Lugol's iodine. The beneficial consequence is that, where
      necessary, DNA sequence data may be obtained from RFTM-cultured tissues, allowing
      the identification of the Perkinsus sp. responsible for an observed infection.
      This would obviate further sampling, representing gain of time and reduction in
      cost, where a Perkinsus sp. is unexpectedly observed in new host(s) or
      location(s) but where parallel samples are not available for molecular
      diagnostics. Laboratories without molecular diagnostic tools for Perkinsus spp.
      may fix presumptive Perkinsus sp.-positive culture material in 95% ethanol for
      transport to, and subsequent analysis by, a laboratory that does have this
      capacity.

PMID- 18814550
TI  - The use of en-bloc pediatric donor transplants.

PMID- 18814551
TI  - Faces: the challenges of minorities with CKD. Part 2 of a four-part series.

PMID- 18814552
TI  - How understanding motivation can improve dialysis practices.

PMID- 18814553
TI  - The importance of self-determination in CKD.

PMID- 18814554
TI  - NxStage creates internet-based registry of HHD patients.

PMID- 18814555
TI  - Registry shows in-center nocturnal most popular.

PMID- 18814556
TI  - KEEP launches follow-up initiative aimed at predicting the future.

PMID- 18814557
TI  - CROWNWeb: the evolution of kidney data management. Part 3 of a three-part series.
AB  - The Centers for Medicare & Medicaid Services is developing a Web-based
      application, CROWNWeb, which is designed to facilitate the mandated entry and
      update of electronic data, and retrieve this data for dialysis facilities
      nationwide. Part III of this three-part series further explores the rationale
      behind CROWNWeb, discusses situations from the past where CROWNWeb could have
      benefited the renal community, and reviews how CROWNWeb can be used in CQI
      activities and to track and improve patient outcomes.

PMID- 18814558
TI  - Modular approach provides competitive edge in provider market.

PMID- 18814559
TI  - Do you know what condition your 'conditions' are in?

PMID- 18814560
TI  - Mentoring for leadership tomorrow: planning for succession today.

PMID- 18814561
TI  - Children's views of their adaptation to type 1 diabetes mellitus.
AB  - When a family learns their child has insulin-dependent type 1 diabetes mellitus,
      or type 1 diabetes, shock and anxiety are quickly followed by the reality of the
      demands of managing the condition. Demands include injections or continuous
      insulin infusion, blood glucose monitoring 2 to 4 times a day, regimented meal
      planning, and intensive planning of daily activities. Like many chronic
      illnesses, type 1 diabetes can have long-term effects on the child and family.
      Health providers must offer support in a number of ways. To determine the best
      way to approach children with diabetes mellitus, this study examined children's
      perceptions of their adaptation to type 1 diabetes. Recognizing children's own
      perceptions is critical for long-term understanding and management. The children
      in this study had overall positive self-perceptions and good attitudes toward
      illness. Even though many adults perceive diabetes mellitus in children as an
      overwhelming experience, the children's attitudes in this study were very
      positive.

PMID- 18814562
TI  - Parental satisfaction with nurses' communication and pain management in a
      pediatric unit.
AB  - This article addresses the relationship between nurses' communication and
      pediatric parents' satisfaction. The study was conducted on a pediatric unit of a
      tertiary care teaching hospital. The design was pre-experimental, measuring
      satisfaction before and after two interventions, without a control group. One
      intervention was an informational handout about pain management provided to
      parents of each child at the time of admission; the other intervention was a
      staff inservice regarding communication with parents. Fifty parents/families of
      discharged patients were randomly chosen for a pre and post-telephone survey,
      routinely conducted each quarter. Parental responses on three items on the
      satisfaction survey were analyzed for significant changes. There were positive
      trends showing increased satisfaction ratings on all three items, but none of the
      increases was statistically significant per t-test (p = 0.05). The authors
      suggest that staff education and a parent informational handout might be useful
      interventions.

PMID- 18814563
TI  - Nurse characteristics and inferences about children's pain.
AB  - The purpose of this study was to describe pediatric nurses' projected responses
      to children's pain as described in vignettes of hospitalized children and to
      explore nurse characteristics that might influence those responses. A survey was
      mailed to a national random sample of 700 RNs, and 334 nurses responded. The
      survey included case reports of three hospitalized school-aged children
      experiencing pain. Nurses were asked to rate their perceptions of the children's
      pain levels and to indicate how much analgesia they would recommend. Contrary to
      earlier studies, in response to the scenarios, nurses in this sample perceived
      high levels of pain, said they would administer doses of analgesia close to the
      maximum prescribed by physicians, and recommended an array of non-pharmacologic
      methods to treat pain. Variation in pain perceptions and decisions was not
      related to key personal and professional characteristics of the nurses, including
      their education level, race/ethnicity, age, years of clinical experience, and
      receipt of continuing education about pain. Findings from this large national
      study suggest that most nurses would make appropriate decisions relating to the
      treatment of children's pain, perhaps reflecting changes in the emphasis on pain
      management.

PMID- 18814564
TI  - Does your facility have a pediatric sedation team? If not, why not?
AB  - Children's hospitals across the country should consider the formation of
      pediatric sedation teams (PSTs) for both in-patient and outpatient pediatric
      procedures. As specialization increases and parents become more in-tune to
      available options, teams that focus on the alleviation of pain and providing a
      more pleasant procedural experience will become increasingly important to parents
      when choosing a facility. Regarding facility benefits, PSTs can assist to improve
      both patient and parent satisfaction, and allow for the relocation of procedures
      to ambulatory care settings or alternative pediatric inpatient suites. PSTs can
      also improve cost effectiveness when sedation is involved by decreasing the
      overall length of stay in procedure rooms and recovery areas, decreasing
      complications related to less experienced providers of pediatric sedation, and
      also decreasing incomplete procedure rates. Parents can be attracted by such
      specialized teams, viewing them as a sign of organizational excellence in the
      care of children's health.

PMID- 18814566
TI  - Ethical perspectives of children's assent for research participation: deontology
      and on utilitarianism.
AB  - Is a child's assent to participate in research that does not have the potential
      to directly benefit the child ethically mandated? Analysis of this particular
      dilemma of health care research in children using two competing theories results
      in different answers. Deontology (principle-based ethics) will be contrasted with
      utilitarianism (consequentialism). Historical cases of research with children
      will be used as exemplars of these two theoretical positions.

PMID- 18814565
TI  - A nurse practitioner's guide to the management of herpes simplex virus-1 in
      children.
AB  - This state of the science clinical article focuses on ways pediatric clinicians
      can manage herpes simplex virus-1 (HSV-1) infections in children and adolescents.
      HSV-1 infections can be transmitted during close contact with asymptomatic and
      symptomatic individuals (Waggoner-Fountain & Grossman, 2004). Recurrent HSV-1
      outbreaks are believed to be caused by various endogenous and exogenous triggers.
      These HSV-1 outbreaks cause physical and emotional consequences in children and
      their families. HSV-1 infections in children most commonly cause
      gingivostomatitis, but these infections can also cause various skin infections,
      including herpetic whitlow, herpes gladiatorum, eczema herpeticum, and herpes
      genitalis. It is critical for pediatric clinicians to be familiar with the
      pathophysiology and clinical manifestations in order to effectively identify,
      manage, and treat HSV-1 infections with a variety of topical or systemic
      medications, as well as with prevention strategies and nutritional
      supplementations.

PMID- 18814567
TI  - Gambling: normal adolescent activity or pathologic addiction?
AB  - A 15-year-old comes to the school counselor. He owes $4,000 in gambling debts to
      a sports-betting bookie, and he doesn't have the money. He is afraid. Yet, 2
      weeks later, he bet on the Super Bowl and won $3,000. A 14-year-old limits his
      betting to $20 and $30; he only bets what he has and he is happy with his
      successes. A 17-year-old was born with a malformed arm and cannot play sports;
      instead, he makes bets on sports games. He sells his belongings to get the money
      he needs; right now, he owes $700. Are the behaviors of these teens unusual?

PMID- 18814568
TI  - Nurses' role in children's environmental health protection.
AB  - There is a growing body of evidence regarding the presence of toxic pollutants in
      the air, water, soil, food, and indoor environments, and the health effects of
      these pollutants on humans. Children have special vulnerabilities to
      environmental risks in their homes, schools, and communities. Children's
      susceptibility to environmental risks stem from biological, behavioral, and socio
      economic factors. Environmental standards are not always protective of children's
      health, and in some instances, no standards exist. Addressing children's
      vulnerabilities and decreasing their exposures require a multi-faceted and multi
      disciplinary approach with clinical, public health, and policy interventions.
      Preventing exposure to hazardous levels of pollution is largely the role of the
      public health community, environmental protection agencies, and the policy makers
      who create the enabling laws. The Institute of Medicine (IOM) (1995) has
      recommended the integration of environmental health into nursing practice,
      education, research, and policy/advocacy work. This article identifies areas in
      each of these categories in which nurses can enhance their practice regarding
      children's environmental health. In addressing children's environmental health,
      nurses' expanded roles can include a range of activities, such as anticipatory
      guidance, health education, public health interface, improved health tracking,
      environmental health research, and legislative/regulatory engagement.

PMID- 18814569
TI  - The evidence on how to best treat sunburn in children: a common treatment
      dilemma.
AB  - While many have suggested that prevention is key regarding sun over exposure,
      individuals (including children) still frequently experience sunburn. The Skin
      Cancer Foundation (2008) reported that 42% of individuals polled endured at least
      one sunburn per year. Furthermore, the Centers for Disease Control and Prevention
      (CDC) reports indicate that the incidence of sunburn rose from 31.8% in 1999 to
      33.7% in 2004 (CDC, 2007). Children are more susceptible to skin damage because
      their skin is more sensitive than the skin of adults and it burns more easily
      (The Skin Cancer Foundation, 2008). Other risk factors include a fair complexion,
      found commonly in people with blueor green eyes, freckles, and light-colored hair
      (The Skin Cancer Foundation, 2008).

PMID- 18814570
TI  - Prediction of the environmental fate and aquatic ecological impact of
      nitrobenzene in the Songhua River using the modified AQUATOX model.
AB  - An accidental discharge of nitrobenzene happened in November 2005 in the Songhua
      River, China. The AQUATOX model was modified and adapted to simulate the time
      dependent nitrobenzene distribution in this multimedia aquatic system and its
      potential ecological impacts. Nitrobenzene concentrations in flowing water,
      sediment, and biota were predicted. Based on the initial concentrations of
      nitrobenzene observed in the field during the accidental discharge, that is,
      0.167-1.47 mg/L at different river segments, the predicted water concentrations
      of nitrobenzene would be lower than 0.02 and 0.002 mg/L after twenty days and one
      month, respectively. Both model prediction and field observation were in good
      agreement. The predicted nitrobenzene concentrations in sediments and aquatic
      organisms would be lower than 0.025 and 0.002 mg/kg, respectively, after two
      months. Among the environmental factors affecting nitrobenzene concentrations in
      water, inflow water dilution, water temperature, and initial concentration were
      the most important, by sensitivity analysis. Comparing the perturbed simulation
      and control simulation, the biomass changes for diatoms and mussel were
      significantly affected, whereas, no influence on other organisms could be
      predicted. Therefore the results indicated that nitrobenzene pollution in the
      Songhua River should have a limited impact on the benthos community.

PMID- 18814571
TI  - Nitrobenzene biodegradation ability of microbial communities in water and
      sediments along the Songhua River after a nitrobenzene pollution event.
AB  - More than 100 t of nitrobenzene (NB) and related compounds were discharged into
      the Songhua River, the fourth longest river in China, because of the world
      shaking explosion of an aniline production factory located in Jilin City on
      November 13, 2005. As one of the efforts to predict the fate of residual NB in
      the river, NB biodegradation abilities by microbes in the water and sediments
      from different river sections were evaluated systematically. The results
      indicated that microbial communities from any section of the river, including one
      section at the upper stream of the NB discharging point, had the ability to
      biodegrade NB under aerobic (for river water samples) conditions at 22 +/- 1
      degree C or anaerobic (for sediment samples) conditions at 10 +/- 1 degree C. NB
      degradation rates of microbial communities in the downstream sites were markedly
      higher than those in the upstream site, indicating that NB degradation abilities
      were enhanced because of the pollution of NB. Aerobic degradation got neglected
      at a temperature of 10 degrees C or lower. The production of nitrosobenzene and
      aniline during aerobic biodegradation suggested the existence of at least two
      different NB degradation pathways, and the occurrence of the catechol-2,3
      dioxygenase (C230) gene and the significant decrease of dissolved organic carbon
      (DOC) indicated that NB could be mineralized under aerobic conditions. Although
      it was a fact that the river have frozen-up during the NB accident, it was
      speculated that biodegradation was not the major process responsible for the
      decrease of NB flux in the river.

PMID- 18814572
TI  - Phototransformation of nitrobenzene in the Songhua River: kinetics and
      photoproduct analysis.
AB  - Nitrobenzene (NB) pollution of the Songhua River caused by an explosion at a
      petrochemical plant in Jilin City, Jilin Province, China, attracted public
      concern over the fate of NB in the river. As one of the efforts to predict the
      fate of residual NB in the river, the kinetics and mechanism of
      phototransformation of NB in natural water from four sections of the Songhua
      River were investigated. It was found that photodegradation of NB in water
      proceeded via pseudo-first-order reaction kinetics under simulated solar
      irradiation conditions, and the rate constant (k) in the ultrapure water system
      was 0.0168 h(-1), which was approximately half of those in the natural river
      water systems (0.323-0.402 h(-1)). The relatively short half-life of NB in
      natural river water systems (17.2-21.5 h) indicates that photodegradation might
      have played an important role in the loss of NB flux in the river. Nitrate
      concentration and alkalinity were the two main factors affecting the
      photochemical fate of NB, suggesting that decomposition of NB mediated by .OH was
      predominant in water solution with high nitrate concentrations. Three isomeric
      nitrophenols, o-, m-, and p-nitrophenols, as well as phenol were detected as the
      main organic products in natural water under natural and simulated solar
      irradiations.

PMID- 18814573
TI  - Characterization of the Songhua River sediments and evaluation of their
      adsorption behavior for nitrobenzene.
AB  - The explosion at a plant of the Jilin Petrochemical Corporation on 13 November,
      2005, and the spill of an estimated 100 t of toxic substances (nitrobenzene as
      the main component) into the Songhua River received worldwide attention. This
      study has focused on the adsorption behavior of nitrobenzene that spilled onto
      sediments along the Songhua River, which was one of the efforts to evaluate the
      fate of nitrobenzene after the spillage event. The organic carbon contents of
      these sediments along the Songhua River varied from 2.1 g TOC/kg at Hulanhekouxia
      to 86.1 g TOC/kg at Jiuzhan. The average volumetric particle diameter also varied
      largely from 11 microm at Jiangchuan to 311 microm at Hulanhekouxia. The sediment
      in the Jiuzhan section showed the highest potential for nitrobenzene adsorption
      (8.3 mg/kg sediment), whereas, that at Hulanhekouxia exhibited the lowest
      adsorption capacity, of 1.6 mg/kg sediment. The nitrobenzene adsorption potential
      is linearly related to the organic carbon content of sediments (R2 = 0.609),
      indicating that the organic carbon content is the main factor affecting the
      adsorption behavior of sediments along the Songhua River. Conclusively, the
      adsorption of nitrobenzene onto the sediments is insignificant, and the release
      of nitrobenzene from sediments is of minor importance.

PMID- 18814574
TI  - Concentration level and geographical distribution of nitrobenzene in Chinese
      surface waters.
AB  - Nitrobenzene was reported to occur at relatively high concentrations in some
      Chinese surface water and to cause an environmental pollution event in 2005. To
      map the distribution of nitrobenzene in the Chinese surface water throughout
      China, surface water samples were collected from over 600 sites in the 7 major
      watersheds and three drainage areas. The samples were analyzed for concentration
      of nitrobenzene. Overall, nitrobenzene was more frequently detected at higher
      concentrations in the rivers of North China, including Songhua River, Liaohe
      River, Haihe River, Yellow River, Huaihe River, and Northwest drainage area
      rivers, compared with those in the rivers of South China, including Yangtze
      River, Pearl River, Southeast drainage area rivers and Southwest drainage rivers.
      The detection rate of nitrobenzene was 83.2% for all the samples, with a mean
      value of 18.1 ng/L and a range of < 0.3-8450.0 ng/L. The highest mean
      concentration of nitrobenzene was observed in the Yellow River, followed by
      Huaihe River. The results of this investigation indicated that nitrobenzene
      should be of particular concern in China and its ecological and health risk
      should be assessed.

PMID- 18814575
TI  - Aqueous oxytetracycline degradation and the toxicity change of degradation
      compounds in photoirradiation process.
AB  - The extensive use of antibiotics has been a worldwide environmental issue. In
      this study the fate of oxytetracycline (OTC), under photoirradiation, was
      investigated. The results showed that OTC photolysis followed first order model
      kinetics. Direct photolysis rate was found to be dependent on the initial OTC
      concentration, with k value ranging from 0.0075 to 0.0141 min(-1), in the OTC
      concentration from 40 to 10 mg/L. OTC photolysis was highly pH-dependent and
      strongly enhanced at a high pH value, with a k value of 0.0629 min(-1) at pH 9.
      Enhanced OTC photolysis has also been observed in the presence of nitrate and low
      concentration of dissolved organic matter. Upon irradiation for 240 min, only
      13.5% reduction of TOC occured in spite of a rapid consumption of 90% of OTC. The
      byproducts from OTC photolysis have been analyzed using high-performance liquid
      chromatography electrospray ionization mass spectrometry (LC-ESI-MS), and the
      degradation pathway of OTC in the photo process was proposed. By employing
      luminescent bacterium to assess the adversity of the degradation compounds, an
      increased effect of toxicity occured in spite of the great consumption of OTC in
      the photoirradiation process. After irradiation for 240 min, the inhibition rate
      was 47%, significantly higher than the initial rate of 21% (p < 0.05), revealing
      a potentially higher adversity risk on the microorganism upon OTC photolysis.

PMID- 18814576
TI  - Heavy metal pollution in Tianjin Bohai Bay, China.
AB  - The contamination levels and distribution characters of heavy metals in coastal
      waters and sediments from Tianjin Bohai Bay, China were examined. Pb and Zn were
      found as the main heavy metal pollutants in the coastal waters of the bay. High
      levels of Pb and Zn appeared especially near the estuary, indicating that river
      discharge was the main pollution source. Moreover, atmospheric deposition
      resulted in Pb contamination in the middle of the embayment. Analysis of data for
      the period 1987-2004 indicated that Pb pollution in coastal waters of Tianjin
      Bohai Bay originated primarily from river discharge before 2001. Pb levels did
      not decrease after 2001 when annual runoff levels declined; indicating that Pb
      pollution by atmospheric deposition had increased due to the use of leaded petrol
      in motorcars. Pb, Zn, and Cd were the dominant polluting elements in surficial
      sediments from Tianjin Bohai Bay, with levels in excess of the corresponding
      upper limits of environmental background values. High concentrations of polluting
      elements were found in tidal sediments near water bodies such as Qihe and Dagu
      estuaries.

PMID- 18814577
TI  - Synthesis and application of lignin-based copolymer LSAA on controlling non-point
      source pollution resulted from surface runoff.
AB  - In this article, alkali lignin separated from paper pulp waste was grafted into a
      novel copolymer LSAA (a copolymer of lignin, starch, acrylamide, and acrylic
      acid). Its practical application effect and environmental safety were studied.
      The results of field simulation experiment indicated that the application of LSAA
      significantly affected the output of the runoff and pollutants. The runoff
      quantity was decreased by 16.67%-47.00% and the loads of total suspended solids
      (TSS), chemical oxygen demand (COD), total nitrogen (TN), and total phosphorus
      (TP) were reduced by 17.78%-62.14%, 26.32%-59.91%, 15.25%-47.42%, and 22.18%
      52.78%, respectively. The tests on its environmental safety showed that LSAA did
      no harm the soil. Compared with polyacrylamide (PAM), a dominant product in this
      field, LSAA exhibited similar effects and cheap cost. Thus, this study not only
      created a new product for controlling runoff water quality but also offered a
      beneficial application for industrial paper waste.

PMID- 18814578
TI  - Comparative equilibrium studies of sorption of Pb(II) ions by sodium and calcium
      alginate.
AB  - The absorption of Pb(II) ions from aqueous solution by different alginate
      compounds was studied in a batch sorption system. Water soluble sodium alginate
      and insoluble calcium alginate beads were investigated. The lead-binding capacity
      of both alginate compounds was highest within the pH range 6-8. The binding
      capacities and rates of Pb(II) ions by alginate compounds were evaluated. The
      Langmuir, Freundlich, and Bruneaur, Emmet and Teller (BET) sorption models were
      applied to describe the isotherms and isotherm constants. Sorption isothermal
      data could be well interpreted by the Langmuir model. The results obtained
      through the study suggest that alginate compounds are favorable sorbents. The
      largest amount of Pb(II) ions were bound by sodium alginate although the
      difference between two compounds was slight. Therefore, alginate substances may
      be considered as an alternative for sorption and removal of Pb(II) ions from
      wastewaters.

PMID- 18814579
TI  - Numerical study on the ozone formation inside street canyons using a chemistry
      box model.
AB  - Tropospheric ozone is a secondary air pollutant produced in the presence of
      nitrogen oxides (NOx), volatile organic compounds (VOCs), and solar radiation. In
      an urban environment, ground-level vehicular exhaust is the major anthropogenic
      source of ozone precursors. In the cases of street canyons, pollutant dilution is
      weakened by the surrounding buildings that creates localized high concentration
      of NOx and VOCs, and thus leads to high potential of ozone formation. By
      considering the major physical and chemical processes, a chemistry box model is
      employed to investigate the characteristics of ozone formation due to vehicular
      exhaust inside street canyons under the worst case scenario, i.e. the calm wind
      condition. It is found that a high level of ozone concentration, of the order of
      100 ppbv and higher, would occur inside the street canyons, in particular, when
      the emission rate (concentration) ratio of VOCs to NOx is greater than 10. This
      elevated ozone concentration appears at the transition from VOCs to NOx
      sensitivity and may extend to a few hundreds.

PMID- 18814580
TI  - Fog simulation using a mesoscale model in and around the Yodo River Basin, Japan.
AB  - In this study, fog simulations were conducted using the Fifth-Generation
      NCAR/Penn State Mesoscale Model (MM5) in and around the Yodo River Basin, Japan.
      The purpose is to investigate the MM5 performance of fog simulation for long-term
      periods. The simulations were performed for January, February, March, and July,
      2005 with a coarse 3-km and a nested fine 1-km grid domains. Results of the
      simulations were compared with data from ten meteorological observatories, fog
      sampling site in Mt. Rokko, and visibility measurement sites along the Second
      Meishin Expressway. At the meteorological observatories, the MM5 predictions
      agreed well with the observed temperature and specific humidity. In the Mt. Rokko
      region, MM5 generally reproduced the occurrence of relatively thick fog events
      but tended to overestimate liquid water content (LWC) of fog (by factors of 2.2
      3.3 in terms of monthly mean LWC). In the Second Meishin Expressway region, while
      MM5 identified the specific sites at which fog either frequently or seldom
      occurs, the model underestimated the monthly fog frequencies by factors of more
      than 1.5. Overall, MM5 reproduced the general trend of fog events, and the model
      performance may be improved by using more adequate land surface data and suitable
      physics options for our study.

PMID- 18814581
TI  - Horizontal distribution and levels of heavy metals in the biggest snowstorm in a
      century in Shenyang, China.
AB  - The horizontal distribution and levels of heavy metals in the biggest snowstorm
      in Shenyang since 1904 were investigated by analyzing 4 metals (As, Cd, Pb, and
      Cu) in a series of ultraclean samples collected from 17 sites distributed in
      different regions of the Shenyang area, China. The results showed that the
      concentrations of all the 4 heavy metals in snow from the industrial regions were
      high, up to 7.3 (As), 2.2 (Cd), 850.0 (Pb), and 0.197-20.2 (Cu) microg/kg,
      respectively. In the suburb, in contrast, their concentrations were not detected,
      except for As. Because of the long-term application of arsenical pesticides and
      herbicides, As was detected in the snow samples which collected on the farm. As,
      Cd, and Pb were also detected in the snow samples collected from the parks, the
      residential areas, and the commercial districts mainly by reason of human
      activities. In a sense, long-term industrial activities, traffic activities, coal
      combustion, and agricultural activities affected the horizontal distribution and
      levels of these heavy metals in snow differently. The data relating to the
      horizontal distribution and concentrations of heavy metals in the snow under
      extreme climatic conditions can provide with a unique snapshot of environmental
      pollution situation and behaviors in urban areas.

PMID- 18814582
TI  - Land-use induced changes in topsoil organic carbon stock of paddy fields using
      MODIS and TM/ETM analysis: a case study of Wujiang County, China.
AB  - Topsoil soil organic carbon (SOC) that plays an important role in mitigating
      atmospheric carbon dioxide (CO2) buildup is greatly affected by human activities.
      To evaluate the influence of land-use changes on SOC stocks in paddy soils, a new
      algorithm was developed by integrating MODIS (moderate resolution imaging
      spectral-radiometer) and TM/ETM data for timely monitoring the land-use change in
      Wujiang County. Thereafter, the land-use class-maps derived from MODIS and TM/ETM
      analyses were further used to estimate land use-induced carbon (C) pool changes
      in paddy topsoil of Wujiang County based upon the nationwide arable soil
      monitoring data and county level SOC reconnaissance data in 2003. The results
      showed that irrigation-based rice cultivation in Wujiang County has resulted in
      SOC content at an annual increasing rate of 0.01 g/kg over the period of 1984
      2003, while the density of SOC in uplands and woodlands has decreased. Annual
      decreasing rate of SOC content was estimated to be 0.03 g/kg in uplands and 0.06
      g/kg in woodlands. The total topsoil SOC stocks in paddy fields of Wujiang County
      have increased from 2.67 x 10(6) t C in 1984 to 2.69 x 10(6) t C in 2005. During
      1984-2005, the total SOC sequestrations in rice paddies were greater than the SOC
      losses in woodlands and uplands. The temporal C loss might have exceeded the SOC
      sequestration in rice paddies due to their conversion to nursery lands and
      uplands since 2001. The results of this study suggest that changes of land use
      have a great influence on soil C sequestration, particularly on C stocks and C
      sequestration potential in paddy fields in developed areas of China.

PMID- 18814583
TI  - Environmental behaviors of selenium in soil of typical selenosis area, China.
AB  - Daba Mountain area is one of the two endemic selenosis areas in China, which may
      relate with the environmental behaviors of selenium (Se) in soil. This study
      focuses on the concentraion and distribution of Se and its relationships with
      some other elements in natural soil in the area. The average concentration of Se
      in Daba Mountain soils was 14.3 times higher than the value cited for natural
      soil background worldwide, suggesting that soils in the region were contaminated
      by the element. The finding was confirmed by Miller geoaccumulation index
      assessment with 22% slightly polluted, 15% moderately polluted, 11% highly to
      very highly polluted and 8% moderately polluted to highly polluted. Soil Se is
      generally enriched in topsoil, and its distribution is extremely uneven and
      significantly site-specific. However, the concentrations of Se in soils have
      significant positive correlation with them in corresponding parent materials (r =
      0.995, P < 0.01). Besides of Se, the concentrations of elements, such as Ca, Sr,
      V, Cu, Zn, Ni, Mg, Co, and Fe are also obviously abnormal compared with their
      background values of Chinese soil. Selenium behaviors in the region were
      controlled by multifactors: in addition to the parent material, pedogenic
      processes, biologic processes, and element geochemical behaviors also impacted
      the concentration and distribution of selenium in soil.

PMID- 18814584
TI  - Location and PCR analysis of catabolic genes in a novel Streptomyces sp. DUT_AHX
      capable of degrading nitrobenzene.
AB  - A novel strain of Streptomyces sp. DUT_AHX was isolated from sludge contaminated
      with nitrobenzene and identified on the basis of physiological and biochemical
      tests and 16S ribosomal DNA (rDNA) sequence analysis. The optimal degradation
      conditions were as follows: temperature 30 degrees C, pH 7.0-8.0, shaking speed
      150-180 r/min, and inocula 10% (V/V). The strain, which possessed a partial
      reductive pathway with the release of ammonia, was also able to grow on mineral
      salts basal (MSB) medium plates with 2-aminophenol, phenol, or toluene as the
      sole carbon source. Furthermore, the enzyme activity tests showed crude extracts
      of nitrobenzene-grown DUTAHX contained 2-aminophenol 1,6-dioxygenase activity.
      The 17-kb plasmid was isolated by the modified alkaline lysis method and was
      further cured by sodium dodecyl sulphate (SDS) together with 37 degrees C. As a
      result, the cured derivative strain DUTAHX-4 lost the 2-aminophenol 1,6
      dioxygenase activity. The results suggested that the catabolic genes encoding the
      nitrobenzene-degrading enzymes were plasmid-associated. Moreover, the plasmid DNA
      was amplified with degenerate primers by touchdown PCR and an expected size
      fragment (471 bp) was generated. The Blast results revealed that the gene
      encoding a 157 amino acid polypeptide was 39%-76% identical to YHS domain
      protein. The further examination of the plasmid would demonstrate the molecular
      basis of nitrobenzene catabolism in Streptomyces, such as regulation and genetic
      organization of the catabolic genes.

PMID- 18814585
TI  - Soil fungistasis and its relations to soil microbial composition and diversity: a
      case study of a series of soils with different fungistasis.
AB  - Fungistasis is one of the important approaches to control soil-borne plant
      pathogens. Some hypotheses about the mechanisms for soil fungistasis had been
      established, which mainly focused on the soil bacterial community composition,
      structure, diversity as well as function. In this study, the bacterial community
      composition and diversity of a series of soils treated by autoclaving, which
      coming from the same original soil sample and showing gradient fungistasis to the
      target soil-borne pathogen fungi Fusarium graminearum, was investigated by soil
      bacterial 16S rDNA-PCR (polymerase chain reaction) cloning, restriction fragment
      length polymorphism (RFLP), and sequencing. The results showed that the soil
      fungistasis capacity was closely correlated with soil bacterial community
      composition and diversity, such as soil fungistasis declined with the decrease of
      soil bacterial diversity. Meanwhile, the bacterial community composition and
      structure were significantly different along the gradient of soil fungistasis
      tested. alpha-Proteobacteria, beta-Proteobacteria, Flexibacter, and some
      uncultured soil bacteria were contributed to soil fungistasis in combination with
      some other special bacteria (Pseudomonas and Acidobacteria) which were know to be
      key species in suppression of fungal growth.

PMID- 18814586
TI  - Biological transformation, kinetics and dose-response assessments of bound musk
      ketone hemoglobin adducts in rainbow trout as biomarkers of environmental
      exposure.
AB  - Low levels (ng/g) of musk ketone (MK), used as a fragrance additive in the
      formulation of personal care products, are frequently detected in the water and
      other environment. Thus, aquatic organisms can be continuously exposed to MK. In
      this study, kinetics and dose-response assessments of 2-amino-MK (AMK)
      metabolite, bound to cysteine-hemoglobin (Hb) in rainbow trout, formed by
      enzymatic nitro-reduction of MK have been demonstrated. Trout were exposed to a
      single exposure of 0.010, 0.030, 0.10, and 0.30 mg MK/g fish. Twenty-seven Hb
      samples were collected from exposed- and control fish subsequent to exposure
      intervals of 1 d (24 h), 3 d (72 h), and 7 d (168 h). Basic hydrolysis released
      bound AMK metabolite was extracted into n-hexane and then concentrated and
      analyzed by gas chromatography (GC) electron capture negative ion chemical
      ionization (NICI) mass spectrometry (MS) using selected ion monitoring (SIM). The
      presence of the AMK metabolite in Hb extracts was confirmed by agreement of
      similar mass spectral features and retention time with a standard. In the dose
      response study, maximum adduct formation was obtained at the 0.10 mg/g dose with
      an average AMK metabolite concentration of 2.2 ng/g. For kinetics, the highest
      concentration of the AMK metabolite was found to be 32.0 ng/g at 0.030 mg/g dose
      in 3-d sample. Further elimination of the metabolite showed kinetics with a half
      life estimated to be 2 d, assuming first-order kinetics. The metabolite was not
      detected in the control samples, non-hydrolyzed Hb, and reagent blank extracts.
      The detection limit for AMK in the Hb was approximately 0.30 ng/g, based on a
      signal to noise ratio of 3 (S/N = 3).

PMID- 18814587
TI  - Preliminary investigation on the role of microorganisms in the production of
      phosphine.
AB  - The relationships between the phosphine content and various microbial
      populations, activities of different enzymes were investigated firstly. The
      results indicated that the phosphine content of samples from various environments
      was positively related to total anaerobic microorganisms, organic phosphate
      compound-dissolving bacteria, denitrifying bacteria, and the activities of
      alkaline phosphatase and dehydrogenase, with correlation coefficients (R2) up to
      0.93, 0.90, 0.69, 0.79, and 0.82, respectively. Results also showed that the
      phosphine content was not related to total aerobic microorganisms, inorganic
      phosphate compound-dissolving bacteria, sulfate-reducing bacteria, and the acidic
      phosphatase activity. Nutrients such as yeast extract and glucose were added, at
      a time and individually, to normal or autoclaved soil samples. The soil samples
      were inoculated with sulfate-reducing bacterial (SRB) enrichments and/or
      denitrifying bacterial (DNB) enrichment. After incubation for one month at 30
      degrees C, the phosphane content of these samples was analyzed. The results
      indicated that the addition of glucose or yeast extract could greatly increase
      the phosphane content. Moreover, it was revealed that inoculation with SRB or DNB
      could also promote the formation of phosphine. The DNB, however, was more
      efficient in this regard. The highest phosphine content, about 5 times that of
      the control, was detected in the sample that was added with both glucose and
      yeast extract and inoculated with SRB and DNB simultaneously. SRB and DNB were
      enriched for several generations and the phosphane content of different
      generations was analyzed. Furthermore, SRB and DNB enrichments were inoculated
      into different media, in the beginning of enriching, the phosphane content was
      about the same for different enrichments, and differed more significantly as the
      enrichment process was carried further. In fourth generation, the phosphane
      content of DNB enrichment was about 3 times of that of SRB enrichment, indicating
      that the inoculation of different enrichments into different media caused the
      variations of the phosphine content. The highest phosphine content was detected
      in the sample which was inoculated with DNB enrichment into the denitrifying
      medium without nitrate. It is inferred from these results that microorganisms
      play an important role in the production of phosphine in different environments.

PMID- 18814588
TI  - Decomposition and phosphorus release from four different size fractions of
      Microcystis spp. taken from Lake Taihu, China.
AB  - Decomposition of Microcystis is accompanied by the release of phosphorus, during
      bacteria play an important role. A series of experiments were undertaken to
      evaluate the effect of bacteria on the decomposition of Microcystis taken from
      Lake Taihu, China, a lake that is suffering from dense Microcystis blooms. The 16
      experiments involved four size fractions of colonial Microcystis with or without
      the addition of lake sediment and Gram-negative bacterial inhibitor NaN3. The
      highest decomposition rates were recorded for the smallest size Microcystis
      fraction (< 25 microm) with the addition of the sediment. The lowest
      decomposition rates were recorded for the smallest Microcystis fraction without
      the sediment, but with the addition of Gram-negative bacterial inhibitor NaN3.
      The higher decomposition rates in the treatments with NaN3 and sediment suggest
      that Gram-positive bacteria in the sediment are important for the decomposition
      process. Additionally, higher concentrations of total dissolved phosphorus (TDP)
      in the treatments with NaN3 suggest that more phosphorus accumulates in the Gram
      negative bacterial cells around the colony, which may be an important source of
      phosphorus for Microcystis cells. In the no-sediment treatments, the ratios of
      TDP concentration to initial TP concentration were 64%-82%. The results of this
      experiment suggest that both Gram-negative and Gram-positive bacteria play an
      important role in the decomposition of Microcystis cells and the release of
      phosphorus from Microcystis colonies.

PMID- 18814589
TI  - What's your diagnosis? Osteochondritis dissecans.

PMID- 18814590
TI  - Current concepts in joint replacement.

PMID- 18814591
TI  - Arthroscopic double mattress repair in incomplete subscapularis tears.

PMID- 18814592
TI  - Mesenchymal stem cells and fracture healing.

PMID- 18814593
TI  - Results of an initial experience with custom-fit positioning total knee
      arthroplasty in a series of 48 patients.
AB  - The custom-fit approach to total knee arthroplasty in conjunction with removal of
      osteophytes and preservation of ligaments rapidly returned function; restored
      motion, stability, and postoperative mechanical axis alignment; effected high
      patient satisfaction; and had an acceptable clinical outcome.

PMID- 18814594
TI  - Continuous wound catheters: practical considerations for use.

PMID- 18814595
TI  - New concepts in the surgical management of ankle fractures.
AB  - Newer studies on surgical management of ankle fractures have given us a greater
      appreciation of the spectrum of stability for multiple patterns of injury, and
      newer fixation approaches and techniques may allow us to optimize fixation.

PMID- 18814596
TI  - Squeaking in total hip replacement: a cause for concern.

PMID- 18814597
TI  - Squeaking in total hip replacement: no cause for concern.

PMID- 18814598
TI  - Hip resurfacing: yet to be proven.

PMID- 18814599
TI  - The use of hydroxyapatite on press-fit tapered femoral stems.
AB  - The advantage of an HA coating includes superior proximal femoral
      osteointegration and reduced thigh pain, reduced subsidence risk, reduced distal
      wear particle migration, and better preservation of periprosthetic bone quality.
      Furthermore, the survivorship and clinical outcomes are at least comparable to
      cemented and uncoated uncemented systems without any substantial deleterious
      effect of the HA coating like third-body wear or late failures. In our opinion,
      these advantages justify the increased cost. With over 20 years of favorable
      cumulative data, the continued use of HA can be recommended as an effective and
      reliable adjunct to cementless tapered femoral fixation in primary THA.

PMID- 18814600
TI  - The short stem: a thinking man's alternative to surface replacement.

PMID- 18814601
TI  - Acetabular fixation options in total hip replacements.

PMID- 18814602
TI  - Femoral-acetabular impingement.

PMID- 18814603
TI  - Osteonecrosis: resuscitate or replace?

PMID- 18814604
TI  - Acetabular protrusio: a problem in depth.
AB  - We have found that positioning of the acetabular implant into the anatomic
      acetabular location is challenging and an important consideration. This can most
      easily be achieved with careful medial reaming, central bone grafting, and cup
      placement on the rim of the native socket supplemented with screw fixation. Our
      data suggest that uncemented acetabular components have better survivorship than
      cemented cups for the treatment of protrusio deformity about the hip.

PMID- 18814605
TI  - Acetabular cup position: the imperative of getting it right.

PMID- 18814606
TI  - Managing length and stability: the role of the modular neck.

PMID- 18814607
TI  - The chronic dislocator: early and late.

PMID- 18814608
TI  - Distally fixed scaffold technique for the management of Vancouver B3
      periprosthetic fractures.
AB  - Periprosthetic femoral fractures with associated severe bone loss are challenging
      problems to treat. High failure rates are reported throughout the literature for
      the various surgical options. The novel distally fixed scaffold technique is a
      rapid procedure with reduced blood loss and high versatility that allows early
      mobilization. Early results have been promising, but further long-term data are
      required.

PMID- 18814609
TI  - Infection following hip replacement: solution options.
AB  - The key to the optimal management of an acutely infected arthroplasty is an
      expeditious diagnosis with careful assessment of the mode of presentation and
      treatment variables to determine the appropriate management strategy. At our
      institution acute infection is managed early and aggressively with debridement
      and exchange of mobile parts and change of the implant if it is cementless. For
      established chronic infection, each case is considered individually, using single
      stage exchange in selected circumstances (1 in 6 cases). Two-stage exchange with
      an articulating spacer is used in the remainder. Single-stage revision offers
      clinical and economic advantages over a two-stage revision in selected patients,
      and although ongoing evaluation is still in place, currently we have had no
      reinfections in our single-stage revision cohort.

PMID- 18814610
TI  - Cement retention in revision total hip arthroplasty: filling the hole.

PMID- 18814611
TI  - Extensively porous-coated stems: avoiding modularity.

PMID- 18814612
TI  - The jumbo cup: the 95% solution.

PMID- 18814613
TI  - The consequences of isolated liner exchange.

PMID- 18814614
TI  - Arthroscopic facetectomy for severe isolated patellofemoral arthrosis.

PMID- 18814615
TI  - Patellofemoral replacement: the third compartment.

PMID- 18814616
TI  - Patient-based MIS TKA: for everything there is a season.

PMID- 18814617
TI  - Correcting flexion contractures: getting it straight.
AB  - Many factors play a role in causing a flexion contracture associated with TKA.
      The final goal of correction is to achieve and maintain a contracture that is <
      15 degrees. Contractures between 10 degrees and 15 degrees may still be
      symptomatic, and those < or = 10 degrees are rarely a problem. Perioperative and
      intraoperative treatment measures exist to alleviate flexion contractures.
      Intraoperative correction determines the final result in most cases, except in
      inflammatory cases where the preoperative contracture is > 40 degrees. In these
      cases, under anesthesia the preoperative contracture need only be corrected to
      within one-third of its initial amount, and the remainder will usually resolve
      with postoperative physical therapy and serial casting or splinting.

PMID- 18814618
TI  - Patient-specific approach in total knee arthroplasty.

PMID- 18814619
TI  - The Krackow suture: how, when, and why.

PMID- 18814620
TI  - Computer-assisted surgery: a wine before its time.

PMID- 18814621
TI  - Computer-assisted surgery: an evolving technology.

PMID- 18814622
TI  - Measured resection: an outdated technique in total knee arthroplasty.
AB  - Multiple methods may be used to determine correct femoral component rotation
      during TKA. Numerous reports document surgeon inability to precisely identify
      critical bone landmarks when deciding correct femoral component rotation using a
      measured resection methodology. While the author recommends using all available
      methods in combination, use of gap balancing provides a more accurate and
      reproducible way to obtain satisfactory flexion gap stability.

PMID- 18814623
TI  - Measured resection: a valuable tool in TKA.

PMID- 18814624
TI  - The top 10 ways to ruin a perfectly good total knee replacement.

PMID- 18814625
TI  - The consequences of malalignment: are there any?

PMID- 18814626
TI  - Management of bone loss: a potpourri of alternatives.

PMID- 18814627
TI  - Cementing an insert in a well-fixed tibial component.

PMID- 18814628
TI  - Stepping up. Is EMS a short career?

PMID- 18814629
TI  - Don't put that tube in!

PMID- 18814630
TI  - Staging strategy. Pausing too close to the scene forces an entry earlier than
      planned.

PMID- 18814631
TI  - Shocking success. ALS providers need clear understandings of what's behind
      defibrillation.

PMID- 18814632
TI  - Safety questions. Are you providing what your crews need to stay safe?

PMID- 18814633
TI  - The hope of RAES. Can Regional Accountable Emergency Systems transform
      healthcare?

PMID- 18814634
TI  - A good place to work.
AB  - Of the many problems facing EMS, recruitment and retention can seem among the
      most intractable. Google the term paramedic shortage, and you'll get more results
      than you can stand to read. There are no easy answers to this situation, but
      there are agencies out there that have had success in finding and keeping people.
      What are they doing right, and what can we learn from them? Here we examine some
      success stories featuring solutions to personnel paucities that are worth
      replicating.

PMID- 18814635
TI  - Cardiac arrest management: part 1. Understanding the role of Basic Life Support
      in the latest American Heart Association guidelines.
AB  - You've just finished renewing your CPR card at the firehouse, and now you're
      sitting in the day room with your classmates. One of them is frustrated that the
      guidelines keep changing. "First it's five compressions to one breath," he says.
      "Then it's 15 to two, and now 30 to two. And what about shocking first? They just
      can't seem to make up their minds." You liked the class, but you can't help
      thinking about all the cardiac arrests you've been on over the years. For all the
      changes in CPR and the new toys and drugs paramedics use now, very few patients
      seem to get pulses back and walk out of the hospital. You wonder if things will
      change with the new guidelines.

PMID- 18814636
TI  - Recognition and treatment of right ventricular myocardial infarction.
AB  - Thirty to 50% of patients experiencing an inferior wall infarct may also have
      involvement of the right ventricle. Right ventricular infarctions seldom exist
      alone they are almost always seen with an inferior infarct. The coronary artery
      involved is usually an occluded right coronary artery (RCA).

PMID- 18814637
TI  - Advanced clinical insights & practice: ischemic heart disease.
AB  - This issue sees the debut of a new series of continuing education articles. The
      series, Advanced Clinical Insights & Practice, is designed to provide continuing
      education to an ever-expanding realm of paramedicine that needs more of it: the
      critical care transport paramedic. Secondly, and equally important, are the
      benefits that can be reaped by other certification levels reading this feature.
      For EMT-Basics and Intermediates, it will provide a great enhancement to your
      core knowledge, although most of the interventions discussed will be beyond your
      traditional scope. For paramedics, it will augment both your pathophysiological
      understanding and clinical assessment/management skills of diseases and injuries
      discussed. Ultimately though, it is hoped that anyone who reads these articles
      will become a better clinician. The next article will appear in the July issue.

PMID- 18814638
TI  - Beyond the basics: lightning-strike injuries.
AB  - It is estimated that a lightning flash occurs approximately 8 million times per
      day throughout the world. Most strikes are benign and cause little damage to
      property and physical structures; however, when lightning strikes a person or
      group of people, it is a significant medical and potentially traumatic event that
      could lead to immediate death or permanent disability. By understanding some
      basic physics of lightning and pathophysiology of injuries associated with
      lightning strikes, EMS providers will be better prepared to identify assessment
      findings, anticipate complications and provide effective emergency care.

PMID- 18814639
TI  - Combined team training.
AB  - For professions that operate in dynarnic environments, developing and improving
      team performance is a significant issue. Paramedics often utilize advanced, high
      risk, low-frequency clinical procedures such as endotracheal intubation, rapid
      sequence induction, needle chest decompression and surgical airways. These
      procedures are performed in a team environment alongside EMTs and first
      responders. Though these groups (paramedics and EMTs/first responders) operate
      together on scenes, if they come from different organizations, they may rarely
      train together. By combining the training they receive, each of these groups can
      improve their cybernation, or the high degree of preparedness and skill achieved
      when a team performs its individual and collective tasks not only correctly, but
      also with the rapid and smooth automaticity that's the hallmark of high
      performance teams.

PMID- 18814640
TI  - Sowing the seeds. A study of employment expectations of EMT students reveals
      important info for EMS managers.
AB  - Although EMS recruitment and retention issues have been frequently discussed,
      little scientific research has been conducted to determine why people are
      entering and leaving the EMS field. To date no research has been done to analyze
      the demographics of people enrolling in EMT classes and determine what their
      attitudes and expectations are for employment.

PMID- 18814641
TI  - Another way. A public/private partnership brings AEDs to the people of Minnesota.

PMID- 18814642
TI  - Earthworms as ecosystem engineers and the most important detritivors in forest
      soils.
AB  - Earthworms are considered as soil engineers because of their effects on soil
      properties and their influence on the availability of resources for other
      organisms, including microorganisms and plants. However, the links between their
      impacts on the soil environment and the resulting modification of natural
      selection pressures on engineer as well as on other organisms have received
      little attention. Earthworms are known to have a positive influence on the soil
      fabric and on the decomposition and mineralization of litter by breaking down
      organic matter and producing large amounts of fasces, thereby mixing litter with
      the mineral soil. Therefore, they play an important part in changes from one
      humus from to another according to forest succession patterns. Consequently, they
      are also expected to be good bio-indicators for forest site quality and are thus
      useful when planning forest production improvement. Earthworm's populations are
      as indicator that in exploited regions is destruction indicator and reclamation
      plans is nature return indicator. In this study we summarized the current
      knowledge in relation to earthworm's ecology in forest soils as ecosystem
      engineers.

PMID- 18814643
TI  - Effect of mycorrhizae, Thiobacillus and sulfur nutrition on the chemical
      composition of soybean [Glycine max (L.)] Merr. seed.
AB  - A field experiment carried out in a calcareous soil with a low available
      phosphorus to evaluate effectiveness of biofertilizers, mycorrhizae (Glomus
      intraradices) and Thiobacillus sp. inoculation individually or in combination on
      seed yield, oil, protein and some elements (P, Fe, Mn, Zn) concentration in two
      soybean [Glycine max (L.) Merr.] cultivars. The applied treatments were different
      fertilizers with 6 levels (including: NP (control, 12 kg N ha(-1) as urea, 46 kg
      P2O5 ha(-1) as triple super phosphate); NPK (NP + 75 kg K2O ha(-1) as potassium
      sulphate); NPKS [NPK+ S (100 kg S ha(-1))]; NPKST (NPKS + seed inoculation with
      Thiobacillus bacteria); NPKM (NPK + Seed inoculation with mycorrhizae fungi) and
      NPKSTM (NPKS + seed inoculation with Thiobacillus and mycorrhizae) and two
      cultivars (JK and 032). Before planting, soybean seeds were inoculated by
      Bradyrhizobium japonicum in all treatments. Results showed that combined
      inoculation of biofertilizers increased yield, however the highest yield was
      observed in treatment NPKST. Increasing oil content (percentage) was more
      pronounced in treatments NPKM, while most protein content (percentage) increasing
      was observed in NPKS and NPKM. Fe and Zn concentrations were unaffected
      significantly by fertilizer treatments, but NPKSTM showed significantly higher
      value of seed's Mn concentration compared to treatments NP and NPK. Although no
      significant difference was observed in terms ofP concentration of 032 line among
      fertilizer treatments, JK cultivar and NPKSTM caused a significant increasing in
      P concentration compared to NP, NPKS and NPKM. Present results suggested that
      applying biofertilizers i.e., mycorrhizae and Thiobacillus increased soybean
      yield compared to control (NP). Overall, this study demonstrated that soybean
      seed yield and its chemical composition could be affected by biofertilizer
      inoculation.

PMID- 18814644
TI  - Effect of water quality indices on phytoplankton of a sluggish tidal creek in
      Lagos, Nigeria.
AB  - The phytoplankton of a tidal creek in Lagos was investigated for six months
      (September 1998-February 1999). The physico-chemical environment was essentially
      neutral (pH 7.00-7.30), relatively more transparent (> 0.23 m), expressed higher
      conductivity (> 0.10 mS cm(-1)), higher chloride values (> 23.48 mg L(-1)), lower
      nitrate content (< 0.70 mg L(-1)), lower sulphate values (< 0.45 mg L(-1)) and
      phosphate values (< 0.12 mg L(-1)) in the dry months. In the wet months,
      September to November 1998, conductivity (< 0.16 mS cm(-1)), transparency (< 0.80
      m), salinity (< 0.04%), dissolved oxygen (< 24.00 mg L(-1)), chloride (< 24.21 mg
      L(-1)) and phosphate (< 0.21 mg L(-1)) were recorded. The phytoplankton was
      dominated by diatoms (48 pennate forms and 23 centric forms). The other algal
      groups comprised six blue- green algae and six green algae. Species richness (d)
      was high in stations nearer the Lagos lagoon for the six sampling periods.
      Shannon-Weaver index (H1) was lowest in November 1998 and highest in October 1998
      and February 1999 while evenness of species J was low (< 0.71) throughout the
      period. Higher phytoplankton biomass was recorded in the dry months than wet
      months.

PMID- 18814645
TI  - Relationship of growth parameters and nutrients uptake with canola (Brassica
      napus L.) yield and yield contribution at different nutrients availability.
AB  - A field experiment was conducted to evaluate the effect of different nutrients on
      canola (Brassica napus L.) growth parameters, nutrient uptake and ultimately on
      seed yield. For this purpose a split plot experimental design, with 10 treatments
      in 4 replications was carried out in 2004-2005, in silt-clay soil at Baiecola
      Agricultural Research Station, Mazandaran Iran. Canola seed yield, growth
      parameters (CGR, LAI, RGR and NAR), dry matter accumulation and HI and nutrient
      content of the leaf were examined. NPK fertilizers together with S and Zn, singly
      or in combination were applied. The results showed that at treatments T5 (NP), T8
      (NPK), T9 (NPKS) and T10 (NPKZn) the higher seed yield (> 2600 kg ha(-1))
      coincided with TDM > 880 g m(-2) the peak CGR > or = 13.9 g m(-2) day(-1) and the
      maximum LAI > or = 4.1. The higher seed yield at T5, T8, T9 and T10 coincided
      with higher concentrations of nutrients: N, P, K, S and Zn in leaf at flowering
      having > or = 3.40%, > or = 0.25%, > or = 1.53%, > or = 110 ppm and > or = 22.7
      ppm, indicating substantial levels of translocation of nutrients at various
      stages of plant growth and higher number of pods per plant (> or = 179). Combined
      application of NPKZn at T10 resulted in maximum seed yield (3090 kg ha(-1)),
      coinciding with the maximum number of pods per plant (230), maximum TDM (1043 kg
      ha(-1)), maximum CGR (20.09 g m(-2) day(-1)) and maximum LAI (4.69).

PMID- 18814646
TI  - Life cycle characteristics of six Artemia populations from Iran.
AB  - The present study was conducted to achieve the life cycle characteristics of six
      Artemia populations (one bisexual and five parthenogenetic) from Iran. The cysts
      of parthenogenetic strains were collected from Maharlu, Incheh, Varmal and Qom
      salt lakes and Lagoons at the periphery of Lake Urmia. Cysts of the bisexual
      Artemia urmiana were collected from the Lake Urmia. All cysts strains were
      hatched using the standard procedures and the nauplii from all populations were
      reared at 80 g L(-1) at laboratory conditions. Survival and total length of the
      Artemia were measured on days 8, 11, 14, 17, 20 and 23 of culture. Randomly
      selected adult animals were studied for eight reproductive and four life span
      characteristics. The findings showed that parthenogenetic Artemia from Maharlu,
      Incheh lakes and from Lagoons at the vicinity of the Lake Urmia had significantly
      highest (p < 0.05) values of survival rate (73 and 62.8%, respectively) compared
      to bisexual A. urmiana and parthenogenetic strains from Qom and Varmal lakes
      (49.6, 29.2 and 23.2%). No significant differences were observed in all growth
      strain populations when cultured under similar laboratory conditions. Artemia
      populations from Maharlu, Qom lakes and from Lagoons in many occasions had
      significantly highest (p < 0.05) reproductive values compared to other three
      populations including the bisexual A. urmiana. The results showed the highest
      heterogeneity and intrapopulation variations among parthenogenetic population
      strains.

PMID- 18814647
TI  - Environmental parameters affecting the species diversity along the Aliakmon
      River, North Greece.
AB  - The annual distribution of aquatic and coastal macrophytes in five selected sites
      along the Aliakmon River was studied from January 2005 to December 2005 in
      Northern Greece. Soil and water chemical parameters in these sites were also
      evaluated. A total of 75 taxa were recorded belonging to 37 families and 53
      genera. The majority of the macrophytes belonged to coastal plants (76%), whereas
      the rest of the macrophytes belonged to aquatic plants (24%). Species of the
      family Asteraceae were dominant among coastal plants, whereas species of the
      family Potamogetonaceae were dominant among aquatic plants. Soil samples from the
      site of Dam of Veria had higher pH and electric conductivity (80-100 cm depth),
      whereas CaCO3 contents were significantly higher in soil samples from the area of
      P. Prodromos (60-80 cm depth). Most physicochemical water parameters as well as
      selected soil nutrients and major ionic components showed an increase during the
      low charge period (fall) compared to with the high charge period (spring),
      especially in parameters associated with agricultural activity. Furthermore,
      there was an increase in most examined values moving towards the delta of the
      river.

PMID- 18814648
TI  - The effect of intermittent hypoxia on bodyweight, serum glucose and cholesterol
      in obesity mice.
AB  - This article tests mice's indicators of body nutritional metabolism under
      tolerable hypoxic conditions, in order to explore the effects of moderate
      intermittent hypoxia on the bodyweight, blood sugar and blood cholesterol of
      obese mice and to identify the role of leptin in these effects; this study
      applies high-fat diet to establish Mice Obesity Models and observes the
      intervention effects of intermittent hypoxic training in this Model. Small
      healthy mice are classified in 4 groups at random, that is, Group A (Normal),
      Group B (Normal Hypoxia) fed with normal foods and undergoing Intermittent
      Hypoxic Training (IHT), Group C (Fatty-diet) fed with High-Fat and High-Sugar
      (HFHS) foods without IHT and Group D (Fatty-diet and Hypoxia) fed with HFHS foods
      with IHT. After 40 days of feeding and hypoxic training, weigh the mice, measure
      the levels of blood sugar and blood cholesterol with a full automatic biochemical
      analyzer, measure serum leptin concentration by enzyme-linked immunosorbent assay
      (ELISA) technique, inspect liver leptin receptor expression and liver fat slice
      by immunohistochemistry. It is found that compared to control group, after
      experiment, the average bodyweight, blood sugar, blood cholesterol and serum
      leptin concentration in Group C is increased significantly and numerous fat cells
      are distributed in the liver, which indicates that hyperlipemia model has been
      successfully established; after intermittent hypoxic training, the average
      bodyweight, blood sugar, blood cholesterol and liver fat cells distribution
      density and scope in Group B and D are lower than those in Group A and C, while
      serum leptin concentration is increased significantly; liver leptin receptor
      expression in Group D is higher than that in Group C. And hypoxia groups have no
      trauma conclusion. Moderate intermittent hypoxia can reduce bodyweight by
      increasing leptin concentration and enhancing liver leptin expression and it can
      also reduce the level of blood sugar and blood cholesterol and meanwhile prevent
      steatosis in liver cells effectively.

PMID- 18814649
TI  - Enumeration of lactobacilli in the fecal flora of infant using two different
      modified de-Man Rogosa Sharpe media under aerobic and anaerobic incubation.
AB  - Regarding the importance of the presence of intestinal lactobacilli and their
      population in infants, four different treatments were evaluated for Lactobacillus
      isolation efficiency via reduction in the growth of other groups of bacteria
      capable of growing on de-Man Rogosa Sharpe (MRS) medium from fecal samples of 11
      Iranian infants. MRS-Vancomycin (1 mg L(-l)) was used as a base medium and
      application of lactic acid and aerobic incubation of inoculated plates were
      performed as selective factors. Each fecal sample was cultivated as duplicate on
      to the base medium with or without lactic acid to reduce the pH to 5.4 +/- 0.2.
      Half of the plates were incubated aerobically and the rest of them incubated
      under 10% CO2 concentration. Total count and Lactobacillus count of all samples
      were recorded according to the age differences of infants. The counts of false
      positive colonies were recorded with respect to their cell morphology and gram
      reaction in all treatments. Anaerobic incubation of lactic acid modified MRS
      Vancomycin gave the most Lactobacillus percentage coverage, about 93% among the
      Lactobacillus positive samples. Using this treatment, the median Lactobacillus
      count yielded 8.29 log10 cfu g(-1) in the younger and 5.70 log10 cfu g(-1) in the
      elder group. It could be concluded that lactic acid might be a proper pH reducing
      agent when enumeration of lactobacilli from fecal samples is of interest.

PMID- 18814650
TI  - Effect of grape seed extract on lead induced hypertension and heart rate in rat.
AB  - The main objective of this study was to evaluate the potential protective effect
      of red Grape Seed Extract (GSE) on lead induced hypertension (HTN) and Heart Rate
      (HR) in male Wistar rats. The rats were randomly assigned to one of 4 groups:
      Each group received lead acetate (100 ppm in drinking water), GSE (100 mg kg(-1),
      orally) or Lead + GSE for 45 days. Another group assigned as control group
      provided with tap water and regular pellet food. The Systolic Blood Pressure
      (SBP) and heart rate were determined by tail plethysmography coupled to a
      computer system. There was a sustained elevation of SBP in lead exposed rats that
      significantly increased at day 18 (lead treated, 112.7 +/- 2.7 mmHg, vs. control,
      105.6 +/- 2.6 mmHg, n = 10, p < 0.05) and reached a maximum level at day 36 (lead
      treated, 124.9 +/- 2.3 mmHg, vs. control, 103.6 +/- 3.1 mmHg, n = 10, p < 0.001).
      However, the other three groups; showed no significant changes in SBP.
      Furthermore, the heart rate was increased sustainly in lead exposed animals that
      was statistically significant at days 36 and 45 (lead treated group, 404.5 +/-
      9.4 vs. control group, 381.7 +/- 6.7, n = 10, p < 0.05). The blood lead level in
      both lead and lead + GSE treated groups was increased significantly compared with
      control and GSE treated groups (p < 0.001). However, GSE administration had no
      effect on the blood lead level in lead treated group. According to the result of
      this study, it may be concluded that GSE could have beneficial effect in
      protecting the cardiovascular system through its antioxidant activity against
      oxidative stress.

PMID- 18814651
TI  - Fruit properties and genetic diversity of five ber (Ziziphus mauritiana Lamk)
      cultivars.
AB  - The present study was conducted on five ber (Ziziphus mauritiana Lamk) cultivars
      (Komethry, Pakstany, Um-sulaem, Toffahy and Peyuan) grown in Saudi Arabia during
      2005 and 2006 seasons. The aim of the present study was to investigate fruit
      properties (fruit weight, length, diameter, shape, specific gravity, seed weight,
      pulp percentage, total soluble solids (TSS), acidity percentage, TSS/acid,
      vitamin C content total, reducing and non-reducing sugars). Peyuan cv. had the
      heaviest fruit weight, fruit volume and reducing sugar content however, it was
      the lowest in pulp percentage and non-reducing sugars among the five cultivars in
      both seasons. Toffahy cv. had highest fruit diameter and seed weight while, had
      lowest TSS %, vitamin C and total sugars values. Um-sulaem cv. had highest
      acidity percentage and vitamin C content and lowest fruit weight, length and
      TSS/acid. On the other hand, Pakstany cv. had highest percentage of both pulp
      percentage, TSS, total and non-reducing sugars. Finally, Komethry had the longest
      fruit. The molecular characterization and fingerprint identification of the ber
      cultivars was conducted using the ISSR (Inter-Simple Sequence Repeats) technique.
      The ISSR technique was able to uniquely characterize and differentiate between
      the five ber genotypes. Moreover, the genetic similarity tree showed that the
      cultivar Um-slaem is genetically distant from the other four cultivars and the
      two cultivars Pakstany and Komethry were genetically identical.

PMID- 18814652
TI  - Microbial and sensory characteristics of camel meat during refrigerated storage
      as affected by gamma irradiation.
AB  - The present study was undertaken to assess the microbiological profile of fresh
      camel meat and the possibility of improving microbial quality and extending the
      refrigerated storage life of meat by using low-dose gamma irradiation. Camel meat
      samples were subjected to 0 (control), 1.5 and 3 kGy doses and stored at 3 +/- 1
      degrees C. the microbial and sensory attributes were evaluated. Exposure to 1.5
      kGy dose significantly reduced the initial counts of Aerobic Plate Counts (APCs),
      psychrophilic bacteria, Lactic Acid Bacteria (LAB), molds and yeasts,
      Staphylococcus aureus, Listeria monocytogenes and Enterococci. Moreover,
      Pseudomonas, coliforms and Escherichia coli were below the detection levels.
      Irradiation at 3 kGy significantly reduced the initial counts of APCs LAB and
      Enterococci by 99.5, 93.5 and 93.9%, respectively. Pseudomonas, coliforms, S.
      aureus, L. monocytogenes and E. coli were not found at dose of 3 kGy during
      entire storage period, also psychrophilic bacteria and molds and yeasts were
      below the detection levels during 6 days of storage. This study shows that
      irradiation had no significant effects on the sensory attributes of camel meat.
      Refrigerated shelf-life of the meat irradiated at 1.5 and 3 kGy were 15 and 21
      days, respectively, compared to 7 days for non-irradiated controls.

PMID- 18814653
TI  - Abiotic transmission of Rice yellow mottle virus through soil and contact between
      plants.
AB  - The roles of guttation fluid, irrigation water, contact between plants and
      transplantation into contaminated soil in the transmission of Rice yellow mottle
      virus (RYMV) were assessed. RYMV presence and infectivity were tested by Enzyme
      Linked Immunosorbent Assay (ELISA) and by inoculation to susceptible rice
      cultivar BG90-2. The virus was readily detected in guttation fluid collected from
      infected rice plants. Transmission tests from this fluid led to high disease
      incidence (86.6%). Irrigation water collected at the base of infected plants
      growing in pots was less infectious, as inoculations led to disease incidences
      below 40%. No virus was detected and could be transmitted from field-irrigation
      water. Up to 44% healthy rice plants whose leaves were in contact with those of
      infected plants became infected but, no transmission occurred through intertwined
      roots. Transplantation of rice seedling into virus-contaminated soil also led to
      plant infection. However, virus survival in the soil decrease rapidly and
      infectivity was completely lost 14 days after soil contamination. Altogether,
      these results indicated that high planting densities of rice are likely to favour
      secondary spread of rice yellow mottle disease. Transplantation of rice seedlings
      not earlier than 2 weeks after soil preparation should prevent soil transmission
      of the virus. Although guttation fluid is highly infectious its contribution to
      virus infectivity in irrigation water is negligible as field-irrigation water was
      not found to be an infectious source for RYMV.

PMID- 18814654
TI  - Antioxidant responses of two barley varieties to saline stress.
AB  - In this study, we investigated antioxidant responses of activities of Superoxide
      Dismutase (SOD), Catalase (CAT), Ascorbate Peroxidase (APX) and Guaiacol
      Peroxidase (GPX) to saline stress in two barley varieties named Hordeum vulgare
      L. var. Afzal and var. EMB82-12 treated with 50, 100, 200, 300 and 400 mM NaCl
      for 3 days. The MDA content of Afzal plants grown under different salt regimes
      remained nearly constant but it largely increased in EMB82-12 plants under the
      same conditions. There was a linear and significant correlation in CAT, APX, SOD,
      GPX activities in Afzal plants in response to increased salt concentration. The
      strong and positive correlation between antioxidant enzymes and salt
      concentrations, may account for the MDA level of Afzal plants remaining constant
      in response to different salt regimes. In general, the activities of antioxidant
      enzymes were increased in the root and shoot under saline stress. But the
      increase was more significant and consistent in the root. Among the antioxidant
      enzymes, CAT activity was increased the most drastically.

PMID- 18814655
TI  - Prevalence of hypertension among Iranian hemodialysis patients and associated
      risk factors: a nationwide multicenter study.
AB  - The aim of this study is to document the prevalence of HTN and characterize risk
      factors associated with HTN in Iranian hemodialysis patients. Three hundred and
      thirty seven HD patients from 5 university based HD centers around Iran were
      enrolled in the study. Urea reduction ratio was calculated using formula: 100 *
      (1-(urea before HD/urea after HD)). Pearson Chi-square test, independent sample t
      test and one way ANOVA were used for evaluations, where appropriate. Multivariate
      logistic regression model was used for defining independent risk factors. Two
      sided p < 0.05 were considered significant. Patients with diabetes mellitus and
      hypertension as causes of ESRD significantly were more likely to have
      hypertension before and after dialysis (p < 0.05). Patients with conventional
      thrice weekly dialysis (compared to twice), hemodialysis duration of more that 6
      months, acetate type of dialysate, ESRD cause when diabetes mellitus and
      hypertension, were significantly associated with having pre-HD hypertension. We
      also found that hemodialysis center of the capital city had a significant better
      measures compared to other cities (p < 0.05). This study revealed a relatively
      acceptable prevalence of hypertension in our HD population. Nevertheless, because
      of higher prevalence of HTN in HD centers out of capital city, it seems necessary
      that we should urgently pay more attention in promotion of these centers toward
      achieving better outcome with implementing strict guidelines to follow.

PMID- 18814656
TI  - Chemical stress induced by heliotrope (Heliotropium europaeum L.) allelochemicals
      and increased activity of antioxidant enzymes.
AB  - The aims of this study were to evaluate the allelopathic potential of heliotrope
      on some biochemical processes of dodder. The preliminary experiments revealed
      that the effect of aqueous extract of leaves of heliotrope is higher than its
      seeds and roots. So, the aqueous extract of leaves was used in remaining
      experiments. Leaf extracts of 5 g powder per 100 mL H2O inhibited the germination
      of dodder seeds up to 95% and that of radish up to 100%. While, the aqueous
      extract of vine leaves which is a non-allelopathic plant did not have any
      inhibitory effect on these seeds. Vine leaf was used as a control to show that
      the inhibitory effect of heliotrope is due to an inhibitory compound but not due
      to the concentration. The leaf extract of heliotrope at 0.0, 0.1, 1.0, 2, 3, 4
      and 5 g powder per 100 mL H2O reduced the radish seedling growth from 14 cm to
      about 0.5 cm and that of dodder from 7.5 cm to about 0.25 cm. The effects of
      heliotrope allelochemicals on some physiological and biochemical processes of
      radish was also Investigated. The activity of auxin oxidase increased in leaves
      and roots of radish. Suggesting that the reduced radish growth is due to the
      decreased active auxin levels in its leaves and roots. The activity of alpha
      amylase was reduced, so reduction of starch degradation and lack of respiratory
      energy is the prime reason of germination inhibition in dodder and radish seeds.
      The level of soluble sugars increased. This is an indication of reduction of the
      activity of some respiratory enzymes and reduced consumption of these sugars.
      Proline levels were also increased, indicating that, the chemical stress is
      induced by leaf extract. Finally, the activities of GPX and CAT which are
      antioxidant enzymes were increased, along with increased extract concentration.
      These finding shows that the chemical stress induced by leaf extract produces
      super oxide (O2*) and H2O2, which is neutralized to H2O and O2 by these enzymes.

PMID- 18814657
TI  - Hydrogen sulfide removal by Thiobacillus thioparus bacteria on seashell bed
      biofilters.
AB  - The aim of this research is to achieve an efficient and cheap methods to remove
      H2S from the factories emissions. Four serial cylinders are designed, 40 cm in
      height and 15 cm in diameter each. They are filled with bivalve seashells with
      63% porosity which contains Thiobacillus thioparus bacteria to the maximum height
      of 27.5 cm. By mixing phosphoric acid and sodium sulfide, H2S gas is released and
      its concentration is measured as mg m(-3) before injecting into the cylinders. A
      permanent measuring instrument is equipped to control the gas coming out of the
      cylinders. In order to prevent the outdoor environment from pollution, first the
      gas is sent through two activated carbon columns and then sent through a ferrous
      chloride scrubber. Finally it is burnt directly by flames. There were 550 sample
      readings in 15 weeks. The changes in the discharge of the air which carries the
      gas are considered between 1-12 L min(-1) and the concentration of the influent
      pollutant is considered between 1-140 mg m(-3). Also the humidity in the
      atmosphere is fixed between 77-93% and the optimum temperature required for
      growing of the microorganisms is retained between 20.5-30 degrees C. After
      feeding the system for three weeks the efficiency started to increase so that by
      the end of the final week of this research the efficiency reached to 90% with the
      discharge of 6 L min(-1) of the carrier gas. The results achieved from this
      research show that because of not using Filamentous bacteria, clogging did not
      occur in the biological system in biofilters. The amount of head loss in cylinder
      was only 2 mm water and during this research, head loss was the same due to
      unclogging of filter. On the other hand the traditional methods are expensive in
      terms of using chemicals, carbon recycling and using fuel and etc. Therefore
      researchers have started new studies in this field. The above mentioned method,
      according to high efficiency, inexpensiveness and easiness of control and
      maintenance is considered one of the best methods.

PMID- 18814658
TI  - A comparative study of inhibitory effect of human calprotectin on the growth of
      human gingival fibroblast and foreskin fibroblast.
AB  - In the present study, cytotoxicity effects of calprotectin on Human Gingival
      Fibroblast (HGF) and Human Foreskin Fibroblast (HFFF) were compared. For these
      evaluations, both cells were exposed to the different concentrations of
      calprotectin, for 24, 48 and 72 h. Cell proliferation was assessed using MTT
      assay. Our results revealed that growth inhibition of calprotectin on HGF and
      HFFF occur in a dose- and time-dependent manner. Results of this investigation
      showed that sensitivity of HGF cells to cytotoxic effect of human calprotectin
      was more than HFFF. The results indicate that drug resistance process is
      different for the two kinds of fibroblast cells.

PMID- 18814659
TI  - Immunogenicity of neonatal BCG vaccination in children entering primary school.
AB  - This study has been designed to evaluate the immunogenicity of neonatal BCG
      vaccination in children at the age of 7 to 8 years, by skin test using Purified
      Protein Derivative (PPD), as BCG vaccination at birth is a part of routine
      program of immunization in our country, Iran; we decided to study its efficacy
      and also tried to determine if there is any correlation between PPD-test results
      and BCG scar size. This is a comparative study on 150 children (94 males and 56
      females) at the age of 7 to 8 years, who possess neonatal-BCG scar. They were
      chosen from several primary schools in Tabriz-Iran, by simple random sampling and
      tested with 0.1 mL of 5-unit-PPD solution (a product of Iran Institute of Razi);
      then observations recorded. The average diameter of BCG scars were 7.03 mm in
      girls, 5.45 mm in boys and 6.05 for all. The diameter of induration area resulted
      from PPD-test after 72 h was less than 5 mm in 95.33% and 5-9 mm in 4.66% of
      studied children; there was no case with induration area of 10 mm or more at all.
      Every child who developed an induration area of 5 mm or more by PPD test, had a
      BCG scar with the diameter of 5 mm or more. There was a statistically meaningful
      direct correlation between sizes of neonatal-BCG scar and diameter of induration
      area after PPD-test (r = 0.21 and p = 0.008). This study shows that reactivity to
      PPD test (and probably immunity against tuberculosis) decreases as age increases;
      therefore it seems to be necessary to repeat BCG-vaccination in children at the
      age of entering primary school.

PMID- 18814660
TI  - Effect of drying temperature on essential oil content and composition of sweet
      wormwood (Artemisia annua) growing wild in Iran.
AB  - Studies were conducted to show the effect of different temperatures in the drying
      process on the amount and quality of essential oils of sweet wormwood (Artemisia
      annua L.). The sweet wormwood aerial parts were harvested in full blooming time
      from an area around the Siahkal city in north of Iran in September 2005. In order
      to complete drying, the aerial parts were placed at shade (room temperature) and
      in oven at 35, 45, 55 and 65 degrees C temperatures. The aerial parts essential
      oil was extracted by hydrodistillation in a Clevenger apparatus and analyzed by
      GC/MS. Results showed that higher drying temperatures decreased the essential oil
      content, from 1.12% (room temperature) 0.88% (35 degrees C), 0.55% (45 degrees C)
      to 0.50% (55 degrees C) and 0.37% (65 degrees C). Thirty-five components were
      determined in essential oils, which were mostly monoterpenes. The drying
      temperatures had a significant effect on the essential oils composition and
      proportion of the various components, as when the temperature increased, the
      monoterpenes content gradually decreased and vice versa for sesquiterpenes. The
      major components were artemisia ketone and 1, 8 cineol for room and 45 degrees C;
      artemisia ketone, 1, 8 cineol and camphor for 35 and 55 degrees C and beta
      caryophyllene and germacrene D for 65 degrees C temperatures.

PMID- 18814661
TI  - Pregnancy rate following transfer of in vitro produced lamb derived embryos in
      two embryonic stages.
AB  - Ovine embryos were produced by maturation, fertilization and in vitro culture
      (IVM/IVF/IVC) of oocytes collected from slaughtered prepubertal ewes. At 24 h
      post IVM, oocytes were fertilized with fresh semen collected from Lori-Bakhtiari
      breed at a concentration of 1.0 x l0(6) sperm mL(-1). The presumptive ova/embryos
      were transferred into the embryo culture medium at 22-24 h post IVF. Following 4
      to 7 day in culture, embryos (at morula and blastocyst stage, respectively) were
      transferred surgically to the uterine horn of synchronized recipients. Pregnancy
      was diagnosed at day 30 by hormonal assay and at days 55 and 140 of gestation by
      ultrasonography and pregnancies were allowed to go to term. A total of nine ewes
      received 27 embryos (3 embryos/ewe). Five ewes received 15 embryos at morula
      stage and four ewes received 12 embryos at blastocyst stage. From those received
      morula stage embryos one was pregnant on day 30 (20%), though no pregnancy was
      diagnosed on each of days 55 and 140. While from those received blastocyst stage
      embryos, three ewes were pregnant on day 30 (75%) and two ewes (50%) remained
      pregnant on each of days 55 and 140. In conclusion, day 4 IVM-IVF morula stage
      embryos had a lower survival rate than did day 7 IVM-IVF blastocysts embryos,
      following transfer to the synchronized recipient ewes.

PMID- 18814662
TI  - Neonatal jaundice: knowledge and practice of Iranian mothers with icteric
      newborns.
AB  - The present study was conducted on a group of Iranian mothers with icteric
      newborn in order to identify any wrong knowledge and improper practices related
      to the neonatal jaundice. Such an estimate of knowledge and practices of mothers
      may be required for implementing the educational programs on which the preventive
      measures of kernicterus are principally thought to be depended. Between June 2004
      and February 2007, 1666 mothers with icteric newborn hospitalized at a single
      center were enrolled. A questionnaire was used to assess the participants'
      knowledge and practice of neonatal jaundice. A knowledge score was calculated
      based on the responses. The mean knowledge score was 3.38 +/- 1.23 (out of 6).
      About 77% of the mothers had moderate-to-high level of knowledge of neonatal
      jaundice. Approximately one-third of the mothers consulted a physician within 24
      h of appearance of jaundice and 13.8% declared that they waited and managed their
      children with traditional remedies until they sought medical advices.
      Furthermore, 32.2% of the mothers discontinued feeding their icteric offspring
      with colored foods and colostrums. Hence, 42.8% of the mothers acted weakly with
      regard to their icteric offspring. The health care workers were the participants'
      major source of information about neonatal jaundice. The present study determined
      a fairly adequate knowledge of Iranian mothers about the neonatal jaundice with
      incomparable level of related practices. The findings of this study should be
      considered seriously by the local health centers and the medical professionals to
      provide consistent information about jaundice and its causes for the parents.

PMID- 18814663
TI  - Chemical composition of the essential oil of Artemisia absinthium growing wild in
      Iran.
AB  - Studies were conducted to investigate the composition of essential oil of
      wormwood (Artemisia absinthium L.) growing wild in Iran. The wormwood aerial
      parts were harvested in full blooming time from an area between Deylaman and
      Asiabar villages, at Alborz altitudes in Guilan province in September 2005.
      Aerial parts were dried at shade (room temperature) for several days and their
      essential oil was extracted by hydrodistillation method in a Clevenger apparatus
      and analyzed by GC/MS. Results showed that essential oil yield was 1.3%. Twenty
      eight components representing 93.3% of the oil were identified, which were mostly
      monoterpenes. beta-pinene and beta-thujone were the main components, which their
      contents were 23.8 and 18.6% respectively. The largest part of the essential oil
      was formed by hydrocarbon monoterpenes (47.8%). The results proved that chemotype
      of the studied wormwood essential oil was specific and different from other
      wormwood essential oil chemotypes, which have been reported so far.

PMID- 18814664
TI  - Callogenic studies of Achyranthes aspera leaf explant at different hormonal
      combinations.
AB  - With the objective to promote in vitro callus induction, leaf segments of
      Achyranthes aspera were inoculated on basal MS medium supplemented with 3.0%
      sucrose and 0.8% agar with different concentrations of 2,4-D alone and in
      combination with NAA, BAP, IAA, IBA and Zeatin. The explants were maintained in
      growth room at 25 +/- 1 degrees C and 16 h light cycle. The best callus induction
      was obtained with 2,4-D (1.0 and 2.0 mg L(-l)) in combination with NAA (0.5 mg L(
      1)). Callus induction and good texture from leaf explant was also observed at 2,4
      D with BAP. On these combinations morphologically, light green, soft, compact and
      non-embryogenic callus (Type III callus) was observed. While morphology of callus
      and callogenic response was poor at 2,4-D alone or in combination with other
      hormones at different concentrations.

PMID- 18814665
TI  - Final decision. People have a right to live--and a right to die.

PMID- 18814666
TI  - Recognizing and managing futility. Take a proactive approach with tragic events.

PMID- 18814667
TI  - The whole family's sick. A little girl's illness leads to the discovery of a
      lethal threat.

PMID- 18814668
TI  - Restrained behavior. Providers, patients and equipment should all be secured.

PMID- 18814669
TI  - Personnel credentialing. A process to assess competency of EMS providers.

PMID- 18814670
TI  - Something old, something new. Updates on important developments during 2007.

PMID- 18814671
TI  - What are those tubes for? What you need to know about central venous access
      devices.
AB  - Prehospital providers who are trained to access and utilize existing CVADs,
      including Groshong, Hickman, Broviac, PICC lines and implanted ports, will be
      able to establish rapid i.v.s. The CVADs, which should be used in critical
      scenarios like shock, cardiac arrest and critical medical conditions, will allow
      EMS to administer medications and fluids to patients in whom i.v. access may
      otherwise be impossible. Providers should review with their medical directors the
      feasibility and practical application of using these devices, ensuring they have
      the correct training and equipment to use these potentially lifesaving devices.

PMID- 18814672
TI  - Information technology 2008.

PMID- 18814673
TI  - Backbreaking work. What you need to know about lifting and back safety in EMS.
AB  - Geraldine did not look very heavy, but she was wedged between the toilet and bath
      tub. She had slipped while getting out of the tub and was complaining of severe
      hip pain. The room was only big enough for me, my partner and Geraldine, who
      needed to be lifted up and out of the room to the cot in the hallway. The
      question at hand was how to keep Geraldine as pain-free as possible while
      protecting our own backs during the lift and move. Nearly every patient contact
      involves lifting and carrying equipment and patients, which applies forces that
      can potentially injure your back. In this article, we explore lifting and back
      safety for EMS providers.

PMID- 18814674
TI  - Bariatric transport challenges: Part 2.
AB  - In Part 1 in the April issue, we reviewed some basics of bariatric lifting and
      moving. This article examines some practical scenarios of showing how these
      skills can be put to use. Think about how you would handle each of these patients
      if you experienced a clinical encounter with them during duty hours.

PMID- 18814675
TI  - Beyond the basics: the art of critical thinking. Part 2.
AB  - This two-part series has addressed the critical thinking process both through
      discussion and demonstration in the case studies presented here. Indeed, the
      process involves all of the decisions we make in assessment and treatment. It is
      not limited to advanced providers. With the exception of the ECG analysis
      mentioned earlier, all other decisions were based on history and physical exam
      and can be performed by any provider. Thinking is not limited to a particular
      license or certification level. We hope these articles have helped you cross a
      bridge into stronger critical decision-making and farther along the journey of
      being a true prehospital clinician at any level of certification.

PMID- 18814676
TI  - Pediatric toxicology: Part 2. What EMS providers need to know about "one-pill
      killers".

PMID- 18814677
TI  - When the message matters.

PMID- 18814678
TI  - PowerPoints to the people. Delivering quality EMS education to rural areas pays
      off for everyone.

PMID- 18814679
TI  - Parasite. Foreword.

PMID- 18814680
TI  - Prospects for elucidating the phylogeny of the Apicomplexa.
AB  - The Apicomplexa is traditionally considered to contain four clearly defined
      groups, but the phylogenetic relationships among these groups, and their
      subsequent taxonomic arrangement, are currently unclear. Here, I consider five of
      the important criteria that need to be met before radical taxonomic changes are
      made, in relation to phylogenetic analyses. Unfortunately, at least four of these
      criteria indicate that the prospects for elucidating the phylogeny and taxonomy
      of the Apicomplexa are not good in the short term. A lot more pertinent data need
      to be collected, both in terms of taxa sampled and genes sequenced, before any
      concordance among phylogenies is likely to emerge; and someone (e.g. a
      consortium) needs to coordinate the active collection and analysis of these data
      if any worthwhile progress is to be made.

PMID- 18814681
TI  - Molecular dissection of host cell invasion by the apicomplexans: the glideosome.
AB  - Gliding motility is an essential and fascinating apicomplexan-typical adaptation
      to an intracellular lifestyle. Apicomplexan parasites rely on gliding motility
      for their migration across biological barriers and for host cell invasion and
      egress. This unusual substratedependent mode of locomotion involves the concerted
      action of secretory adhesins, a myosin motor, factors regulating actin dynamics
      and proteases. During invasion, complexes of soluble and transmembrane micronemes
      proteins (MICs) and rhoptry neck proteins (RONs) are discharged to the apical
      pole of the parasite, some protein acts as adhesins and bind to host cell
      receptors whereas others are involved in the moving junction formation. These
      complexes redistribute towards the posterior pole of the parasite via a physical
      connection to the parasite actomyosin system and are eventually released from the
      parasite surface by the action of parasite proteases.

PMID- 18814682
TI  - Toxoplasma gondii gene expression is under the control of regulatory pathways
      acting through chromatin structure.
AB  - The activity state of a gene is determined by a complex regulatory network of co
      acting factors affecting the structure of the chromatin into which the gene is
      embedded. While significant changes of the transcriptome occur during cell
      differentiation in apicomplexan parasites, basic mechanisms controlling gene
      expression are still unknown. Recent studies support and expand the concept of
      the chromatin environment being key factor for the control of transcriptional
      activity in these lower eukaryotes organisms. Here, we review recent advances in
      the field of epigenetic gene regulation in Toxoplasma gondii, the model
      apicomplexan.

PMID- 18814683
TI  - Cellular and molecular interactions between the apicomplexan parasites Plasmodium
      and Theileria and their host cells.
AB  - Apicomplexan parasites of the genera Theileria and Plasmodium have complicated
      life cycles including infection of a vertebrate intermediate host and an
      arthropod definitive host. As the Plasmodium parasite progresses through its life
      cycle, it enters a number of different cell types, both in its mammalian and
      mosquito hosts. The fate of these cells varies greatly, as do the parasite and
      host molecules involved in parasite-host interactions. In mammals, Plasmodium
      parasites infect hepatocytes and erythrocytes whereas Theileria infects ruminant
      leukocytes and erythrocytes. Survival of Plasmodium-infected hepatocytes and
      Theileria-infected leukocytes depends on parasite-mediated inhibition of host
      cell apoptosis but only Theileria-infected cells exhibit a fully transformed
      phenotype. As the development of both parasites progresses towards the merozoite
      stage, the parasites no longer promote the survival of the host cell and the
      infected cell is finally destroyed to release merozoites. In this review we
      describe similarities and differences of parasite-host cell interactions in
      Plasmodium-infected hepatocytes and Theileria-infected leukocytes and compare the
      observed phenotypes to other parasite stages interacting with host cells.

PMID- 18814684
TI  - Discovery of new targets for antimalarial chemotherapy.
AB  - The understanding of the biology and the biochemistry of malaria parasites has
      considerably increased over the past two decades with the discovery of many
      potential targets for new antimalarial drugs. The decrypted genomes of several
      Plasmodium species and the new post-genomic tools further enriched our
      "reservoir" of targets and increased our ability to validate potential drug
      targets or to study the entire parasite metabolism. This review discusses targets
      involved in calcium metabolism, protein prenylation and apicoplast functions that
      have emerged by different approaches.

PMID- 18814685
TI  - Kinetoplastid phylogenetics, with special reference to the evolution of parasitic
      trypanosomes.
AB  - To fully understand the evolutionary history of parasitic kinetoplastids and to
      understand the context within which the evolution of each parasite group has
      developed, an understanding not just of the parasites, but of all kinetoplastids
      is required. Accordingly, this paper provides an overview of kinetoplastid
      evolution and systematics, including coverage of the proposal by Moreira et al.
      (2004) to divide kinetoplasts into Prokinetoplastina (Ichthyobodo and
      Perkinsiella) and Metakinetoplastina (other bodonids and trypanosomatids). The
      implications of such a revision, with regard to correctly identifying outgroup
      taxa for studies of evolution within taxa of medical importance, are addressed,
      together with a more detailed review of the evolution and origins of the
      trypanosomes in the light of new phylogenies, new approaches and revisions in
      kinetoplastid systematics.

PMID- 18814686
TI  - Molecular epidemiology of African trypanosomiasis: the contributions of David
      George Godfrey OBE to the biochemical characterization of trypanosomes.
AB  - The accurate identification of the causative organisms of disease is fundamental
      to the study of epidemiology. Hence molecular tools are now widely used to detect
      and distinguish pathogens, and have greatly improved our understanding of
      epidemiology. David Godfrey pioneered the use of molecular markers in the
      epidemiology of African trypanosomiasis, thus enabling the light of reliable
      evidence to shine on this previously problematic and controversial subject area.
      From the early 1970's David's group employed first isoenzyme electrophoresis and
      subsequently DNA-based characterization methods to aid identification of
      typanosomes collected from a range of endemic countries across Africa. These
      investigations had a major impact on our understanding of the zoonotic nature of
      human trypanosomiasis in Africa and of the genetic diversity of African
      trypanosomes.

PMID- 18814687
TI  - Molecular crosstalks in Leishmania-sandfly-host relationships.
AB  - Sandflies (Diptera: Phlebotominael are vectors of Leishmania parasites, causative
      agents of important human and animal diseases with diverse manifestations. This
      review summarizes present knowledge about the vectorial part of Leishmania life
      cycle and parasite transmission to the vertebrate host. Particularly, it focuses
      on molecules that determine the establishment of parasite infection in sandfly
      midgut. It describes the concept of specific versus permissive sandfly vectors,
      explains the epidemiological consequences of broad susceptibility of permissive
      sandflies and demonstrates that genetic exchange may positively affect Leishmania
      fitness in the vector. Last but not least, the review describes recent knowledge
      about circulating antibodies produced by hosts in response to sandfly bites.
      Studies on specificity and kinetics of antibody response revealed that anti
      saliva IgG could be used as a marker of host exposure to sandflies, i.e. as a
      useful tool for evaluation of vector control.

PMID- 18814688
TI  - Borrelia burgdorferi sensu lato, the agent of lyme borreliosis: life in the
      wilds.
AB  - In Europe, Borrelia burgdorferi sensu lato (sl) the agent of Lyme borreliosis
      circulates in endemic areas between Ixodes ricinus ticks and a large number of
      vertebrate hosts upon which ticks feed. Currently, at least 12 different Borrelia
      species belonging to the complex B. burgdorferi sl have been identified among
      which seven have been detected in I. ricinus: B. burgdorferi sensu stricto (ss),
      B. garinii, B. afzelii, B. valaisiana, B. spielmanii and B. bissettii. A few
      dozens of vertebrate hosts have been identified as reservoirs for these Borrelia
      species. Specific associations were rather early observed between hosts, ticks
      and borrelia species, like for example between rodents and B. afzelii and B.
      burgdorferi ss, and between birds and B. garinii and B. valaisiana. The
      complement present in the blood of the hosts is the active component in the
      Borrelia host specificity. Recent studies confirmed trends toward specific
      association between Borrelia species and particular host, but also suggested that
      loose associations may be more frequent in transmission cycles in nature than
      previously thought.

PMID- 18814689
TI  - Treatment of scabies infestations.
AB  - Scabies is an intensely pruritic disorder induced by an immune allergic response
      to infestation of the skin by the mite Sarcoptes scabiei. The biology of the
      mite, the clinical aspects and diagnosis of scabies infestations as well as the
      treatment of choice with 5% permethrin dermal cream and the use of scabicides
      based on other chemical substances are reviewed.

PMID- 18814690
TI  - Sandfly pheromones. Their biology and potential for use in control programs.
AB  - Lutzomyia longipalpis (Diptera: Psychodidae) is the vector of Leishmania chagasi
      the causative agent of visceral leishmaniasis (VL) in South and Central America,
      particularly Brazil, where the greatest incidence occurs. The disease is fatal if
      untreated. Although huge efforts have been made to control VL the incidence is
      increasing. Vector control remains an important element of disease control but
      residual spraying and other strategies have failed to make any lasting impact.
      Manipulation of sandfly chemical communication offers the opportunity to add new
      techniques and tools to reduce sandfly populations and thereby reduce Leishmania
      transmission. This paper reports the current understanding of several areas of
      sandfly chemical ecology and their prospects for application.

PMID- 18814691
TI  - Biodiversity and extinction versus control of oestrid causing myiasis in
      Mediterranean area.
AB  - Oestrid larvae causing myiasis display a wide degree of biodiversity, in terms of
      species of domestic and wild mammals infected and anatomical sites. The presence
      in some regions of southern Europe of a high number of different species of
      oestrids in domestic animals stimulated interest in exploring the basis of such
      degree of parasitic biodiversity in the Mediterranean region. However, broad
      spectrum anti-parasitic treatments (e.g. macrocyclic lactones) constitute a
      critical factor for the selection of species of Oestrids and for the maintenance
      of their biodiversity in a given area. The dynamic equilibrium that oestrid
      larvae have established with the host and the environment as well as the span of
      biodiversity they represent may be considered to be at odds with maintaining
      animal welfare and reducing animal production losses.

PMID- 18814692
TI  - Pathophysiology of enteric infections with Giardia duodenalius.
AB  - Giardia is the most prevalent human intestinal parasitic protist in the world,
      and one of the most common parasite of companion animals and young livestock.
      Giardia is a major cause of diarrhea in children and in travelers. The host
      microbial interactions that govern the outcome of infection remain incompletely
      understood. Findings available to date indicate that the infection causes
      diarrhea via a combination of intestinal malabsorption and hypersecretion.
      Malabsorption and maldigestion mainly result from a diffuse shortening of
      epithelial microvilli. This enterocytic injury is mediated by activated host T
      lymphocytes. Pathophysiological activation of lymphocytes is secondary to Giardia
      induced disruption of epithelial tight junctions, which in turn increases
      intestinal permeability. Loss of epithelial barrier function is a result of
      Giardia-induced enterocyte apoptosis. Recent findings suggest that these effects
      may facilitate the development of chronic enteric disorders, including
      inflammatory bowel disease, irritable bowel syndrome, and allergies, via
      mechanisms that remain poorly understood. A newly discovered SGLT-1 glucose
      uptake-mediated host cytoprotective mechanism may represent an effective
      modulator of the epithelial apoptosis induced by this parasite, and, possibly, by
      other enteropathogens. A better understanding of the pathogenesis of giardiasis
      will shed light on new potential therapeutic targets.

PMID- 18814693
TI  - Trophozoites of Entamoeba histolytica epigenetically silenced in several genes
      are virulence-attenuated.
AB  - The human intestinal parasite Entamoeba histolytica causes amoebic colitis and
      amoebic liver abscesses. Three classes of amoebic molecules have been identified
      as the major virulence factors, the Gal/GalNAc inhibitable lectin that mediates
      adherence to mammalian cells, the amoebapores which cause the formation of
      membrane ion channels in the target cells and the cysteine proteinases which
      degrade the matrix proteins, the intestinal mucus and secretory IgA.
      Transcriptional silencing of the amoebapore (Ehapa) gene occurred after
      transfection of trophozoites with a plasmid containing a segment of the 5'
      upstream region of the gene. Transcriptional silencing of the Ehap-a gene
      continued even after the removal of the plasmid and the cloned amoebae were
      termed G3. Transfection of G3 trophozoites with a plasmid construct containing
      the cysteine proteinase (EhCP-5) gene and the light subunit of the Gal- lectin
      (Ehlgl1) gene, each under the 5' upstream sequences of the amoebapore gene,
      caused the simultaneous epigenetic silencing of expression of these two genes.
      The resulting trophozoites, termed RB-9, were cured from the plasmid and they do
      not express the three types of virulent genes. The RB9 amoeba are virulence
      attenuated and are incapable of killing mammalian cells, they can not induce the
      formation of liver abscesses and they do not cause ulcerations in the cecum of
      experimental animals. The gene-silenced amoebae express the same surface antigens
      which are present in virulent strains and following intra peritoneal inoculation
      of live trophozoites into hamsters they evoked a protective immune response.
      Further studies are needed to find out if RB-9 trophozoites could be used for
      vaccination against amoebaisis.

PMID- 18814694
TI  - Drug treatment and novel drug target against Cryptosporidium.
AB  - Cryptosporidiosis emergence triggered the screening of many compounds for
      potential anti-cryptosporidial activity in which the majority were ineffective.
      The outbreak of cryptosporidiosis which occurred in Milwaukee in 1993 was not
      only the first significant emergence of Cryptosporidium spp. as a major human
      pathogen but also a huge waterborne outbreak thickening thousands of people from
      a major city in North America. Since then, outbreaks of cryptosporidiosis are
      regularly occurring throughout the world. New drugs against this parasite became
      consequently urgently needed. Among the most commonly used treatments against
      cryptosporidiosis are paromomycin, and azithromycin, which are partially
      effective. Nitazoxanide (NTZ)'s effectiveness was demonstrated in vitro, and in
      vivo using several animal models and finally in clinical trials. It significantly
      shortened the duration of diarrhea and decreased mortality in adults and in
      malnourished children. NTZ is not effective without an appropriate immune
      response. In AIDS patients, combination therapy restoring immunity along with
      antimicrobial treatment of Cryptosporidium infection is necessary. Recent
      investigations focused on the potential of molecular-based immunotherapy against
      this parasite. Others tested the effects of probiotic bacteria, but were unable
      to demonstrate eradication of C. parvum. New synthetic isoflavone derivatives
      demonstrated excellent activity against C. parvum in vitro and in a gerbil model
      of infection. Newly synthesized nitro- or non nitro- thiazolide compounds,
      derived from NTZ, have been recently shown to be at least as effective as NTZ
      against C. parvum in vitro development and are promising new therapeutic agents.

PMID- 18814695
TI  - Biodiversity of flukes.
AB  - As many others parasites, speciation of flukes depends on the genetic
      characteristics and on ploidia. Ploidia of flukes can be different in a same
      species. In Asia, diploid, triploid and hybrid (2n/3n) populations are
      encountered. The comparison of morphological parameters between diploid and
      triploid flukes showed that they were morphologically different. Nevertheless, a
      genetic relationship between parthenogenetic organisms would exist regardless of
      their ploidia. In the Fasciola genus, the main consequence of the high level of
      diversity is the frequent probability of development of resistance to
      anthelmintics and fast adaptation to climatic changes. In the Paragonimus genus,
      diversity can enhance different forms of pathogenicity, can also be related to
      the species of intermediate hosts, and to the definitive host. The strain of
      flukes plays a part in the visceral localization of P. westermani adults.

PMID- 18814696
TI  - The influence of host hormones and cytokines on Echinococcus multilocularis
      signalling and development.
AB  - Parasitic helminths display highly complex life-cycles in which the establishment
      of adults or larvae within host target organs as well as the transition of one
      developmental stage to the following is influenced by host-derived factors. Due
      to its approachability concerning in vitro cultivation, the larval stage of the
      fox-tapeworm Echinococcus multilocularis has recently emerged as a model system
      to study the molecular nature of such host-derived stimuli and their influence on
      developmental control in the parasite. Data obtained so far indicate that
      cytokines which are used by the host for cell-cell communication can also be
      exploited by the parasite as clues to find suitable target organs. This involves
      direct interactions of evolutionary conserved signalling systems of the receptor
      tyrosine--and the receptor serine/threonine-kinase pathways of the parasite with
      corresponding host cytokines of the insulin-, the epidermal growth factor-, and
      the transforming growth factor-beta-families. In the present article, we will
      briefly review in vitro cultivation approaches undertaken so far for E.
      multilocularis larvae as well as our current knowledge on the parasite's
      signalling systems and their interaction with host cytokines.

PMID- 18814697
TI  - Current trends in tissue-affecting helminths.
AB  - Some helminths have by their evolution learnt to systemically invade a host
      organism, and to select specific organs or host cell types as predilection site
      to reside, maturate or even proliferate. These parasites needed to develop
      complex and unique strategies to escape host immune reactions. The present work
      sheds some light into the strategy developed by three different helminths
      (Echinococcus multilocularis, Trichinella spiralis and Toxocara conis) to survive
      in the host organ or host cell, respectively. The crucial role of periparasitic
      host reactions that may help the host to control the parasite, but which may also
      be responsible for immunopathological events harmful to the host himself, are
      elucidated as well. Finally, for these three parasites selected, the murine host
      appears an acceptable model for carrying out experimental studies, as for these
      parasites, rodents as well as humans become infected in the parasites natural
      life cycle. Therefore, conclusions drawn from murine experiments may provide much
      more reliable data in view of their relevance for the human infection, a fact
      that frequently lacks when using mice as experimental model for other helminths.

PMID- 18814698
TI  - Penetration of Trichobilharzia cercariae into mammals: dangerous or negligible
      event?
AB  - Bird schistosomes and cases of human cercarial dermatitis occur worldwide, but
      the number of cases is not monitored. Experiments with two schistosomes, namely
      Trichobilharzia szidati and T. regenti, show that they possess potent tools to
      penetration bird and mammalian skin, as well as exhibit species-specific
      migration patterns within vertebrate bodies. Therefore, the infections may affect
      different organs/tissues e.g. lungs or spinal cord. In this minireview, the
      adaptations and pathogenic effects of bird schistosomes in experimental mammals
      are discussed, and some ideas/hypotheses on risks to humans from exposure to bird
      schistosome cercariae are expressed.

PMID- 18814699
TI  - The compatibiuty polymorphism in invertebrate host/trematodes interactions:
      research of molecular determinants.
AB  - The co-evolutionary dynamics that exist in many host-parasite interactions
      sometimes leads to compatibility polymorphism. This phenomenon is well documented
      in mollusc/trematodes interactions but its molecular base is unknown. In order to
      identify key molecules involved in this phenomenon, we developed several
      molecular approaches comparing compatible or incompatible strains of mollusc or
      parasite. These comparisons led to the identification of numerous candidate genes
      listed and discussed (some of them) in the present review.

PMID- 18814700
TI  - Plant-nematode interactions: environmental signals detected by the nematode's
      chemosensory organs control changes in the surface cuticle and behaviour.
AB  - Plant parasitic nematodes have developed the capacity to sense and respond to
      chemical signals of host origin and the ability to orientate towards plant roots
      enhances the nematode's chance of survival. Root exudates contain a range of
      compounds which mediate belowground interactions with pathogenic and beneficial
      soil organisms. Chemical components of root exudates may deter one organism while
      attracting another and these compounds alter nematode behaviour and can either
      attract nematodes to the roots or result in repellence, motility inhibition or
      even death. In vitro, plant signals present in root exudates, trigger a rapid
      alteration of the surface cuticle of Meloidogyne incognita and the same changes
      were also induced by indole-acetic acid (IAA). IAA binds to the chemosensory
      organs of M. incognito and it is possible that IAA acts as a signal that
      orientates the nematode on the root surface in the rhizosphere and/or inside the
      root tissue and thereby promotes nematode infection.

PMID- 18814701
TI  - Cryptic diversity in intestinal protists.
AB  - In the past few years our understanding of genetic variation within and between
      species of intestinal parasitic protists has changed significantly. New species
      names have been assigned and others have been dropped in response to new data. In
      this review, I summarise these findings and discuss their implications for future
      studies. In several cases the findings suggest that caution needs to be exercised
      to prevent premature conclusions being reached.

PMID- 18814702
TI  - Annelids in evolutionary developmental biology and comparative genomics.
AB  - Annelids have had a long history in comparative embryology and morphology, which
      has helped to establish them in zoology textbooks as an ideal system to
      understand the evolution of the typical triploblastic, coelomate, protostome
      condition. In recent years there has been a relative upsurge in embryological
      data, particularly with regard to the expression and function of developmental
      control genes. Polychaetes, as well as other annelids such as the parasitic
      leech, are now also entering the age of comparative genomics. All of this
      comparative data has had an important impact on our views of the ancestral
      conditions at various levels of the animal phylogeny, including the bilaterian
      ancestor and the nature of the annelid ancestor. Here we review some of the
      recent advances made in annelid comparative development and genomics, revealing a
      hitherto unsuspected level of complexity in these ancestors. It is also apparent
      that the transition to a parasitic lifestyle leads to, or requires, extensive
      modifications and derivations at both the genomic and embryological levels.

PMID- 18814703
TI  - Lophotrochozoan relationships and parasites. A snap-shot.
AB  - Lophotrochozoa has been consistently recovered in molecular phylogenetic analyses
      using different markers. Current knowledge of lophotrochozoan relationships is
      reviewed and the place that parasites occupy in this phylogeny is discussed. Two
      major taxa are identified within Lophotrochozoa: Platyzoa and Trochozoa.
      Monophyly of both taxa is still under debate. Relationships within Trochozoa
      remain largely unclear, however, there is strong evidence that the so called
      "minor phyla" Sipuncula, Echiura, and Myzostomida are all nested within annelids.
      Monophyly of the former "Lophophorata" is rejected, and a close relationship
      between phoronids and brachiopods, as well as between bryozoans and kamptozoans
      is suggested instead. The movement of the field of systematics into the genomic
      era will greatly improve our knowledge in the near future.

PMID- 18814704
TI  - Platyhelminth systematics and the emergence of new characters.
AB  - Since the inclusion of molecular data in modern phylogenetic analyses,
      significant progress in resolving the origins and radiation of flatworms has been
      made, although some key problems remain. Here I review developments in the supply
      and use of systematic characters that provide the basis for diagnosis and
      phylogeny reconstruction, that in turn have driven systematic revisions and the
      interpretation of broader evolutionary patterns and processes; focus is placed on
      the parasitic taxa. Although useful tools have been refined to the point of
      becoming established systematic markers of broad utility, attention to the need
      for denser gene and taxon sampling is addressed in the light of unresolved
      questions and current trends in molecular systematics, from nucleotide to genome.
      Tradition and the nature of available comparative information tends to dictate
      the choice of systematic markers, but faced with incongruent phylogenies, the
      emergence of new technologies and the need for rapid species diagnosis, there is
      a pressing need to assess and standardize our choice of tools so they are fit for
      purpose, available to all and used widely. I present a brief review of existing
      and potential sources of phylogenetic characters and discuss their likely value
      in the context of the systematics and diagnostics of parasitic flatworms.

PMID- 18814705
TI  - The nematoda Filarioidea: critical analysis linking molecular and traditional
      approaches.
AB  - The molecular analysis of the Filarioidea and the endobacteria Wolbachia is no
      more limited to the agents of human diseases and the diversified sampling permits
      a synthesis with the morphological and biological results. The validity of the
      genera with "uncoherent host range", such as Monsonella, Litomosoides and
      Cercopithifilaria, is confirmed and, consequently, their evolution by host
      switchings. Dirofilaria and Onchocerca, types of two subfamilies, appear more
      closely related than with other onchocercids. Waltonellinae from anurans and
      Oswaldofilariinae from reptiles have a basal position. These filariae, and some
      others also considered primitive, do not harbour Wolbachia. Evidence for
      transversal transmission of the bacteria and a second acquisition event is given
      with the supergroup F, identified in Monsonella, in one of the Cercopithifilaria
      species and in arthropods.

PMID- 18814706
TI  - Enterocytozoon bieneusi in human and animals, focus on laboratory identification
      and molecular epidemiology.
AB  - Human microsporidian infections have emerged following the onset of the AIDS
      pandemic. Microsporidia are unicellular eukaryotic parasites that form spores.
      They are an exceptionally diverse group of parasites that infect a wide range of
      eukaryotic cells in numerous invertebrate and vertebrate hosts. Of the 14 species
      newly described as pathogens in human, Enterocytozoon bieneusi, which causes
      gastrointestinal diseases, is the most common agent of human infections. In the
      past fifteen years, E. bieneusi was also identified in environmental sources,
      especially in surface water, as well as in wild, domestic and farm animals. These
      findings raised concerns for waterborne, foodborne and zoonotic transmission.
      Molecular analyses of the 243-bp internal Transcribed spacer-(ITS) of the rRNA
      gene have revealed a considerable genetic variation within E. bieneusi isolates
      of human and animal origins, supporting the potential for zoonotic transmission.
      The focus of this revue is to present and discuss recent advances in diagnosis
      and zoonotic potential of E. bieneusi infections.

PMID- 18814707
TI  - Nosocomial Pneumocystis jirovecii infections.
AB  - Airborne transmission of Pneumocystis sp. from host to host has been demonstrated
      in rodent models and several observations suggest that interindividual
      transmission occurs in humans. Moreover, it is accepted that the Pneumocystis
      organisms infecting each mammalian species are host specific and that the
      hypothesis of an animal reservoir for Pneumocystis jirovecii (P. jirovecii), the
      human-specific Pneumocystis species, can be excluded. An exosaprophytic form of
      the fungus cannot be strictly ruled out. However, these data point toward the
      potential for the specific host to serve as its own reservoir and for
      Pneumocystis infection in humans as an anthroponosis with humans as a reservoir
      for P. jirovecii. This review highlights the main data on host-to-host
      transmission of Pneumocystis in rodent models and in humans by the airborne route
      and provides a rationale for considering the occurrence of nosocomial infections
      and measures for their prevention

PMID- 18814708
TI  - Toxoplasma gondii, "new" genotypes and virulence.
AB  - Toxoplasma gondii has been described as a parasite with a low genetic diversity
      and a clonal population structure. The three main clonal lineages designated as
      type I, II or III largely predominate in Europe and North America. But strains
      not related to these main lineages circulate, notably, in other continents. They
      possess a shuffled combination of alleles that typify the three clonal types and
      unique polymorphisms detected by multilocus analysis. The population structure of
      Toxoplasma in these continents is also characterized by a higher genetic
      diversity associated with a lower linkage desequilibrium suggesting a role for
      genetic exchange. Due to their genomic diversity, it is difficult to draw global
      conclusions about their virulence. However, most of them are virulent in mice at
      isolation. Several reports also suggest a higher pathogenicity in humans and an
      association with ocular toxoplasmosis or severe cases of acquired toxoplasmosis
      in immunocompetent patients.

PMID- 18814709
TI  - Cryptosporidium: from laboratory diagnosis to surveillance and outbreaks.
AB  - The burden of disease caused by the protozoan parasite Cyptosporidium is unknown.
      However, routine laboratory diagnosis and surveillance enables the basic
      epidemiology to be described, changes to be monitored and under-ascertainment to
      be measured. Although the two main species involved in human disease in developed
      countries, Cryptosporidium parvum and Cryptosporidium hominis, have differing
      epidemiologies and risk factors, national surveillance is generally from isolates
      identified to the genus level only. Enhancing the data by typing, at least to
      identify the isolates to the species level, removes some of the noise generated
      and better identifies the risks than when reports are not species-specific. This
      level of identification is also valuable for outbreak investigations, but further
      investigation of the population genetics of C. parvum and C. hominis is required
      for the development of more readily applied subtyping tools.

PMID- 18814710
TI  - Protective immunity against malaria liver stage after vaccination with live
      parasites.
AB  - Despite nearly 100 years of research and control efforts, malaria remains one of
      the most important infectious diseases. An efficient vaccine would be a powerful
      to tool to reduce mortality and morbidity. Experimentally, induction of sterile
      immunity in humans after vaccination with attenuated sporozoites has been
      obtained. This observation has spurred the search for subunit vaccines that aim
      to reproduce this protection. As yet none of the current candidate subunit
      vaccines achieved complete protection reproducibly. This failure coupled to the
      recent advent of genetically modified Plasmodium parasites has led to a renewed
      interest in the use of live parasites for vaccination against malaria pre
      erythrocytic stages. In this article, we review and discuss the recent
      developments in this field.

PMID- 18814711
TI  - Role of natural killer T lymphocytes during helminthic infection.
AB  - Natural killer (NK)T cells are innate lymphocytes that release important amount
      of immunoregulatory cytokines (IFN-gamma and/or IL-4) shortly after T cell
      receptor engagement by (glyco)lipid antigens presented by the CD1d molecules.
      Through this property, NKT cells play pivotal role in many physiopathologic
      situations. Here, we review the current knowledge of the functions and mechanisms
      of activation of NKT cells during infection, with a particular emphasis on
      helminthic infections. Recent findings suggest that, although dispensable for
      host resistance, NKT cells play part in the development of the acquired immune
      response and in the control of the pathology during murine schistosomiasis.

PMID- 18814712
TI  - Mucosal immunity in Toxoplasma gondii infection.
AB  - Toxoplasma gondii is an intracellular parasite that frequently infects a large
      spectrum of warm-blooded animals. This parasite induces abortion and establishes
      both chronic and silent infections, particularly in the brain. Parasite
      penetration into the host activates a strong anti-parasite immune response. In
      the present paper, we will discuss the interplay between innate and adaptive
      immunity that occurs within the infected intestine to clear the parasite and to
      maintain intestinal homeostasis despite the exacerbation of an inflammatory
      immune response.

PMID- 18814713
TI  - Alternative life cycle strategies of Megalodiscus temperatus in tadpoles and
      metamorphosed anurans.
AB  - Megalodiscus temperatus (Stafford, 1905) is a common paramphistome trematode of
      North American amphibians with a two host life cycle and has been reported to
      infect frogs and rarely tadpoles. In this study we document the alternative life
      cycle strategy of M. temperatus in tadpoles and metamorphosed anurans. We show
      through field work and experimental infections that M. temperatus can establish
      in both anuran life stages and worms become gravid and release eggs in both
      tadpoles and metamorphosed frogs. However, worms exhibit differences in route of
      infection, development, egg production, and diet in tadpoles and metamorphosed
      anurans. These alternative life history strategies of M. temperatus suggest
      different selective pressures on the development and reproductive success of
      these worms in tadpoles and metamorphosed anurans, and we discuss the
      evolutionary avenues for and constraints on amphibian trematode life cycles
      presented by these two different anuran life stages.

PMID- 18814714
TI  - Use of nuclear and mitochondrial DNA PCR and sequencing for molecular
      identification of Diphyllobothrium isolates potentially infective for humans.
AB  - Tapeworms of the genus Diphyllobothrium (Cobold, 1858) are widely distributed all
      around the world and some of them are agents of human diphyllobothriasis.
      Approximately 50 species have been described within the Diphyllobothrium genus
      but only 13 are human pathogens. Species identification by using morphological
      criteria is very difficult. We determined the value of 18S ribosomal RNA gene,
      internal transcribed spacer (ITS) and cytochrome c oxidase subunit 1 gene (COI)
      sequences to differentiate between Diphyllobothrium isolates. Sequences from 18
      isolates (larvae or adults) of D. latum, D. nihonkaiense, D. ditremum, D.
      dentriticum and D. stemmacephalum species were obtained. COI region sequences
      analysis was clearly more discriminative than those of the ITS1 and 18S rRNA and
      was a useful tool for identifying specimens.

PMID- 18814715
TI  - Genetic relationships among species of Contracaecum Railliet & Henry, 1912 and
      Phocascaris Host, 1932 (Nematoda: Anisakidae) from pinnipeds inferred from
      mitochondrial cox2 sequences, and congruence with allozyme data.
AB  - The genetic relationships among 11 taxa, belonging to the genus Contracaecum (C.
      osculatum A, C. osculatum B, C. osculatum (s.s.), C. osculatum D, C. osculatum E,
      C. osculatum baicalensis, C. mirounga, C. radiatum, C. ogmorhini (s.s.), C.
      margolisi) and Phocascoris (Phocoscris cystophorae), parasites as adults of
      seals, were inferred from sequence analysis 1519 bp) of the mitochondrial
      cytochrome c oxidase subunit II (mtDNA cox2) gene. Phylogenetic analyses obtained
      from Parsimony (MP) and Neighbour-Joining (NJ) K2P distance values generated
      similar topologies, each well supported at major nodes. All analyses delineated
      two main clades: the first encompassing the parasites of the phocid seals, i.e.
      the C. osculatum species complex, C. osculatum boicolensis, C. mirounga and C.
      radiatum, with the latter two species forming a separate subclade; the second
      including the parasites of otarids, i.e. C. ogmorhini (s.s.) and C. margolisi. An
      overall high congruence between mtDNA inferred tree topologies and those produced
      from nuclear data sets (20 allozyme loci) was observed. Comparison of the
      phylogenetic hypothesis here produced for Controcaecum spp. plus Phocascaris with
      those currently available for their definitive hosts (pinnipeds) suggests
      parallelism between hosts and parasite phylogenetic tree topologies.

PMID- 18814716
TI  - Fish immune response to Myxozoan parasites.
AB  - Myxozoan parasites are responsible for important economic losses among fisheries
      and aquaculture industries, and hence the high interest in studying the immune
      response of fish against them. The most important data available concerning the
      immune response of fish against myxosporeans are reviewed, with emphasis on the
      different innate and adaptive immune mechanisms, their relationship with natural
      and acquired resistance and the strategies to control and prevent myxosporoses.
      Cellular effectors (lymphocytes, granulocytes, phagocytes, non-specific cytotoxic
      cells, rodlet cells) and humoral factors (lysozyme, peroxidades, antiproteases,
      complement, specific antibodies) have been examined for several myxosporoses, and
      some immune relevant genes have been studied. This information will be crucial
      for the future development of vaccines and other preventive strategies such as
      immunomodulation and selection of disease-resistant strains

PMID- 18814717
TI  - The inflammatory response of fish to helminth parasites.
AB  - Fish serve as a good model for studying vertebrate immune systems because they
      have a relatively simple system. Descriptions of histopathological effects of
      helminth parasites on fish are few and far between with limited observations made
      on the identification of the inflammatory cells involved in the host reaction.
      Recently, two cell types found within teleosts received a great deal of
      attention, namely mast cells and rodlet cells. Fish most cells also known as
      eosinophilic granule cells, are morphologically and functionally similar to their
      mammalian counterparts. Acute tissue damage causes mast cells degranulation and
      the release of mediators of inflammation, whereas, an increase in the number of
      these cells is usually found in chronically inflamed tissues. Rodlet cells,
      however, are exclusive to fish and are characterized by a distinct cell cortex
      and conspicuous inclusions, called rodlets, which accounts for their name.
      Piscidin has also been encountered within rodlet cells. As important cell types
      within the immune system of fish, both mast cells and rodlet cells have been seen
      to increase in number in infected fish, notably at the sites of pathogen
      attachment or infection. The present survey will provide data from studies with
      the light microscope on the response of mast cells and rodlet cells in a range of
      fish species (Anguilla anguilla, Oncorhynchus mykiss, Salmo trutta, Coregonus
      lavoretus) infected with a range of different parasite genera including
      representatives from the Digenea, Cestoda, Nematoda and Acanthocephala.

PMID- 18814718
TI  - Environmental parasitology. Interactions between parasites and pollutants in the
      aquatic environment.
AB  - In recent years there has been an increasing number of papers showing how
      parasitism and pollution can interact with each other in aquatic organisms. Among
      the variety of investigated aspects especially the combined effects of pollution
      and simultaneous infection on the health of aquatic hosts (molluscs, crustaceans,
      fish, mammals) is of considerable interest. Effects of pollution on the
      occurrence and distribution of parasites is another interesting field of
      "Environmental Parasitology" attracting increasing attention. This mini-review
      presents some promising examples of interdisciplinary studies paying attention to
      the fact that under natural conditions no organism will only be affected by
      either parasites or pollution.

PMID- 18814719
TI  - Parasite co-structure: broad and local scale approaches.
AB  - A co-structure study is a comparison of demographic and/or genetic structure
      between two or more species. Such a comparative analysis among a parasite and its
      host(s) or among multiple parasite species is useful to elucidate factors that
      shape genetic variation within and among parasite populations. I provide a brief
      review of how co-structure studies in parasite systems can be used to address
      ecological, evolutionary, and epidemiological questions. Subjects that can be
      addressed with parasite costructure studies range from broad-scale analyses that
      compare phylogeographical patterns to local scale analyses that examine among
      host transmission within a host population.

PMID- 18814720
TI  - The population genetic structure of vectors and our understanding of disease
      epidemiology.
AB  - Understanding and predicting disease epidemiology relies on clear knowledge about
      the basic biology of the organisms involved. Despite the key role that arthropod
      vectors play in disease dynamics and detailed mechanistic work on the vector
      pathogen interface, little information is often available about how these
      populations function under natural conditions. Population genetic studies can
      help fill this void by providing information about the taxonomic status of
      species, the spatial limits of populations, and the nature of gene flow among
      populations. Here, I briefly review different types of population genetic
      structure and some recent examples of where this information has provided key
      elements for understanding pathogen transmission in tick-borne systems.

PMID- 18814721
TI  - Population genetics of fungal diseases of plants.
AB  - Although parasitism is one of the most common lifestyles among eukaryotes,
      population genetics on parasites lag for behind those on free-living organisms.
      Yet, the advent of molecular markers offers great tools for studying important
      processes, such as dispersal, mating systems, adaptation to host and speciation.
      Here we highlight some studies that used molecular markers to address questions
      about the population genetics of fungal (including oomycetes) plant pathogens. We
      conclude that population genetics approaches have provided tremendous insights
      into the biology of a few fungal parasites and warrant more wide use in
      phytopathology. However, theoretical advances are badly needed to best apply the
      existing methods. Fungi are of prime interest not only because they are major
      parasites of plants and animals, but they also constitute tractable and highly
      useful models for understanding evolutionary processes. We hope that the emerging
      field of fungal evolution will attract more evolutionary biologists in the near
      future.

PMID- 18814722
TI  - The impact of clonalty on parasite population genetic structure.
AB  - In this paper, we briefly review the consequences of clonal reproduction on the
      apportionment of genetic diversity in parasite populations. We distinguish three
      kinds of parasite lifecycle where clonal reproduction occurs. The consequences of
      this mode of reproduction for the different kinds of parasite life-cycles are
      described. We here particularly focus on clonal diploids.

PMID- 18814723
TI  - Molecular markers and sentinel organisms for environmental monitoring.
AB  - Molecular methods are useful for both to monitor anthropogenic viral, bacterial,
      and protozoan enteropathogens, and to track pathogen specific markers in a
      complex environment in order to reveal sources of these pathogens. Molecular
      genetic markers for fecal viruses, bacteria, and protozoans hold promise for
      monitoring environmental pollution and water quality. The demand for
      microbiologically safe waters grows exponentially due to the global demographic
      rise of the human population. Economically important shellfish, such as oysters,
      which are harvested commercially and preferentially consumed raw can be of public
      health importance if contaminated with human waterborne pathogens. However, feral
      molluscan shellfish which do not have an apparent economic value serve as
      indicators in monitoring aquatic environments for pollution with human waterborne
      pathogens and for sanitary assessment of water quality. Current technology allows
      for multiplexed species-specific identification, genotyping, enumeration,
      viability assessment, and source-tracking of human enteropathogens which
      considerably enhances the pathogen source-tracking efforts.

PMID- 18814724
TI  - Spatial and temporal modelling for parasite transmission studies and risk
      assessment.
AB  - Spatial and temporal modelling of parasite transmission and risk assessment
      require relevant spatial information at appropriate spatial and temporal scales.
      There is now a large literature that demonstrates the utility of satellite remote
      sensing and spatial modelling within geographical information systems (GIS) and
      firmly establishes these technologies as the key tools for spatial epidemiology.
      This review outlines the strength of satellite remotely sensed data for spatial
      mapping of landscape characteristics in relation to disease reservoirs, host
      distributions and human disease. It is suggested that current satellite
      technology can fulfill the spatial mapping needs of disease transmission and risk
      modelling, but that temporal resolution, which is a function of the satellite
      data acquisition characteristics, may be a limitating factor for applications
      requiring information about landscape or ecosystem dynamics. The potential of the
      Modis sensor for spatial epidemiology is illustrated with reference to mapping
      spatial and temporal vegetation dynamics and small mammal parasite hosts on the
      Tibetan plateau. Future research directions and priorities for landscape
      epidemiology are considered.

PMID- 18814725
TI  - Multidisciplinary studies, systems approaches and parasite eco-epidemiology:
      something old, something new.
AB  - Parasite requires an understanding of complex transmission systems where
      individual, population and environmental factors and their interactions can
      hardly been considered separately. Moreover, the importance of space and time in
      host population and parasite transmission processes is increasingly recognised.
      The present review illustrates how epidemiology and transmission ecology have
      evolved in a multidisciplinary framework to a systems approach that includes both
      spatial and temporal dimensions. Focusing on population processes, three
      significant challenges are discussed: (i) integration of landscape ecology
      concepts and modelling across time-space scales, (ii) development of molecular
      methods that permits easy parasite/host identification and process tracking (e.g.
      host and parasite movements), and (iii) integration of sociology methods to
      estimate zoonotic risk and exposure.

PMID- 18814726
TI  - Evaluating parasite densities and estimation of parameters in transmission
      systems.
AB  - Mathematical modelling of parasite transmission systems can provide useful
      information about host parasite interactions and biology and parasite population
      dynamics. In addition good predictive models may assist in designing control
      programmes to reduce the burden of human and animal disease. Model building is
      only the first part of the process. These models then need to be confronted with
      data to obtain parameter estimates and the accuracy of these estimates has to be
      evaluated. Estimation of parasite densities is central to this. Parasite density
      estimates can include the proportion of hosts infected with parasites
      (prevalence) or estimates of the parasite biomass within the host population
      (abundance or intensity estimates). Parasite density estimation is often
      complicated by highly aggregated distributions of parasites within the hosts.
      This causes additional challenges when calculating transmission parameters. Using
      Echinococcus spp. as a model organism, this manuscript gives a brief overview of
      the types of descriptors of parasite densities, how to estimate them and on the
      use of these estimates in a transmission model.

PMID- 18814727
TI  - PCR-based methods to the diagnosis of imported malaria.
AB  - Rapid and precise diagnosis of malaria is needed to take care febrile patient
      returning from endemic areas. Since the first description of the diagnosis of
      Plasmodium infection by polymerase-chain-reaction (PCR), the role of this kind of
      molecular method in the laboratory diagnosis of imported malaria is still a
      topical question. PCR-based assays were found to be more sensitive and more
      specific than all conventional methods. The highest contribution of the molecular
      diagnosis is that a PCR negative result would ascertain the lack of any malaria
      infection, thus quickly orienting the investigations toward other aetiology. This
      technique should be now considered as the gold standard for the diagnosis of
      imported malaria.

PMID- 18814728
TI  - Current bioethical issues in parasitology.
AB  - Parasitic diseases constitute the most common infections among the poorest
      billion people, entailing high mortality rates and leading to long-term
      infirmities and poverty. Although the setting-up of public health programs
      implies many ethical consequences, the range of specific questions in
      parasitology that can be attributed to bioethics remains, to a large extent,
      unexplored. From the present analysis, it emerged three main issues which
      characterize ethical stakes in parasitology: accounting the complexity of the
      field of intervention, putting the principle of justice into practice and
      managing the changing context of research. From the research angle, medical
      parasitology-mycology, as other biological disciplines, is undergoing tensions
      derived from biological reductionism. Thanks to its links with the history and
      philosophy of the sciences, bioethics can help to clarify them and to explain the
      growing hold that technologies have over scientific thinking. On the whole,
      researchers as well as clinicians are called on to assume a specific
      responsibility, proportional to their competence and their place in the making of
      scientific, health, economic and social decisions.

PMID- 18814729
TI  - Manson's triple error.
AB  - The author discusses the significance, implications and limitations of Manson's
      work. How did Patrick Manson resolve some of the major problems raised by the
      filarial worm life cycle? The Amoy physician showed that circulating embryos
      could only leave the blood via the percutaneous route, thereby requiring a
      bloodsucking insect. The discovery of a new autonomous, airborne, active host
      undoubtedly had a considerable impact on the history of parasitology, but the way
      in which Manson formulated and solved the problem of the transfer of filarial
      worms from the body of the mosquito to man resulted in failure. This article
      shows how the epistemological transformation operated by Manson was indissociably
      related to a series of errors and how a major breakthrough can be the result of a
      series of false proposals and, consequently, that the history of truth often
      involves a history of error.

PMID- 18814730
TI  - The scientific research programmes of Lakatos and applications in parasitology.
AB  - The methodology of scientific research programme (MSRP) proposed by Lakatos was
      in the line of the proposals made by Popper. MSRP were intended for constructing
      and evaluating research programme, which is unique among philosophers of science.
      Surprisingly, scientists dedicated to research in mathematics, physic or biology
      have not used much MRSP. This could be due to the fact that scientists are not
      aware of the existence of MSRP, or they find it difficult to apply to their own
      investigations. That is why we present firstly the main characteristics of this
      methodology (hard core--the group of hypothesis that are admitted by experts in
      the field, auxiliary hypotheses--which are intended to protect and refine the
      hypotheses of the hard-core, and heuristics for mending and evaluating the MSRP)
      and, secondly, propose an example in helminthology. We think that the methodology
      of Lakatos, is a useful tool, but it cannot encompass the large flexibility of
      investigations pathways.

PMID- 18814731
TI  - Pro and cons of targeted selective treatment against digestive-tract strongyles
      of ruminants.
AB  - The increasing prevalence of resistance to anthelmintics among gastrointestinal
      nematodes and the desire for lower input agriculture have promoted the idea that
      targeted selective treatment (treating the animals in need of such a treatment
      and only them) could be a sustainable solution for controlling internal parasites
      of ruminants. The pros are the slowing of resistance prevalence, lower residues
      of anthelmintics in meat and milk, and lower cost; the cons are the difficulty
      and time spent on selecting animals in need of treatment and the possibility of
      lower production. Using actual experiments and modelling we show that targeted
      selective treatment can be used to sustainably control gastrointestinal nematode
      infections in flock.

PMID- 18814732
TI  - Onchocerciasis control: biological research is still needed.
AB  - Achievements obtained by the onchocerciasis control programmes should not lead to
      a relaxation in the biological research on Onchocerco volvulus. Issues such as
      the Loa loa-related post-ivermectin serious adverse events, the uncertainties as
      to whether onchocerciasis can be eliminated by ivermectin treatments, and the
      possible emergence of ivermectin-resistant O. volvulus populations should be
      addressed proactively. Doxycycline, moxidectin and emodepside appear to be
      promising as alternative drugs against onchocerciasis but support to researches
      in immunology and genomics should also be increased to develop new control tools,
      including both vaccines and macrofilaricidal drugs.

PMID- 18814733
TI  - Towards a vaccine against pregnancy-associated malaria.
AB  - The consequences of pregnancy-associated malaria on pregnant women (anaemia),
      their babies (birth weight reduction), and infants (increased morbidity and
      mortality) are well documented. Field observations during the last decade have
      underlined the key role of the interactions between P. falciparum variable
      surface antigens expressed on infected erythrocytes and a novel receptor:
      chondroitin sulfate A (CSA) for the placental sequestration of infected
      erythrocytes. Identification of a distinct P. folciparum erythrocyte membrane
      protein 1 (PfEMP1) variant, VAR2CSA, as the dominant variant surface antigen and
      as a clinically important target for protective immune response to
      pregnancyassociated malaria has raised hope for developing a new preventive
      strategy based on inducing these immune responses by vaccination. However,
      despite particular structure and interclonal conservation of VAR2CSA among other
      PfEMP1, significant challenges still exist concerning the development of a
      VAR2CSA-based vaccine with profound efficacy.

PMID- 18814734
TI  - Kinetoplastida: new therapeutic strategies.
AB  - New formulations and therapeutic switching of the established drugs, amphotericin
      B and paromomycin, together with the discovery of miltefosine, have significantly
      improved the opportunities for treatment of visceral leishmaniasis (VL)
      chemotherapy. However, for human African trypanosomiasis (HAT), Chagas disease
      and cutaneous leishmaniases there has been limited progress. For HAT, a novel
      diamidine, parfuramidine, is in phase III clinical trial for early-stage disease,
      but for the treatment of late-stage disease there are no new drugs and
      combinations of eflornithine with melarsoprol or nifurtimox have been the focus
      of clinical studies. For Chagas disease, different classes of compounds that have
      validated biochemical targets, sterol biosynthesis methylases and cysteine
      proteases, are in various stages of development. The genome sequences that are
      now available for the pathogens that cause the leishmaniases and trypanosomiases,
      and new methods for rapid validation of targets, are part of the solution to
      discover new drugs. The integration of medicinal chemistry, pharmacokinetics,
      project planning and interaction with the pharma/biotech sector are essential if
      progress is to be made. Although there are financial constraints, the appearance
      of new funding sources and not-for-profit product development partnerships offers
      hope for drug development.

PMID- 18814735
TI  - Hard times. People are struggling and our job's getting bigger.

PMID- 18814736
TI  - Lose your breath. Maintain your perspective on the things that really matter in
      life.

PMID- 18814737
TI  - The mess in the garage. An accident with a saw poses opportunities for great
      customer service.

PMID- 18814738
TI  - Talk to you tomorrow. Interview by Raphael M Barishansky.

PMID- 18814739
TI  - Who signs what, and how often? What you need to know about new signature
      requirements.

PMID- 18814740
TI  - "Level with me, sugar!" Dealing with diabetics and diabetic emergencies.

PMID- 18814741
TI  - It's about time. The mistake we make in this crazy business is to think that the
      small-time components are what matter the most.
AB  - Few things weave their way through all aspects of what we do like the clock. Make
      your response times (less than 8 minutes, 59 seconds 90% of the time), have fast
      hospital turn-around, do two minutes of compressions prior to shock, ventilate if
      you can't get the Stube in 15 seconds, transport people who are shot to the
      trauma center in less than 10 minutes after you reach them, give your estimated
      time of arrival to the hospital, count the minutes between contractions, give epi
      every 5 minutes, show up to work on time, donate time to plan the holiday party,
      work overtime, take time to relax, make time for your family, and, and, and. It's
      time we had a frank talk about stress, myths, tricks and traps of the most common
      unit of measurement in EMS.

PMID- 18814742
TI  - The air that you breathe. What you need to know about OSHA's Respiratory
      Protection Standard.

PMID- 18814743
TI  - Just point and click. Is your system ready for point-of-care testing?
AB  - Your ALS service is called to evaluate a 47-year-old female with epigastric pain
      that came on suddenly about six hours ago; she has vomited once. She thought it
      was the flu and that it would subside, but it has not. She smokes, is overweight
      and has a family history of early cardiac disease. Her vital signs are
      unremarkable and her belly is nontender. You perform a 12-lead ECG that shows
      nonspecific ST-T wave changes inferiorly. You place a few drops of blood obtained
      as part of your field-drawn bloods into an i-STAT cartridge. The result surprises
      you: Her cardiac enzyme (troponin I) is markedly elevated. Should she be
      transported to the closer facility without primary coronary intervention (PCI)
      capability or further down the road to a facility that has it?

PMID- 18814744
TI  - Beyond the basics: interpreting altered mental status assessment findings.
AB  - EMS providers frequently encounter patients who are not alert and present with an
      altered mental status, meaning their level of brain function is in question.
      Various physical examination techniques are employed during the assessment to
      determine the level of cerebral function and integrity of the brainstem. It is
      important to understand the limitations of these techniques, as well as potential
      findings that may cause you to erroreously interpret, re port and document the
      level of brain function. This information is often used to identify trends to
      determine if the patient's condition is deteriorating, remaining the same or
      improving.

PMID- 18814745
TI  - Navigating the generation gap.
AB  - Many EMS managers are struggling with a new workforce challenge that has snuck up
      on them: for the first time ever the workforce is populated with four distinct
      generations working side by side. Each has needs different from their managers'
      and unique ideas about their ideal workplace. How can you satisfy them all? By
      understanding and managing to each of the generations.

PMID- 18814746
TI  - Making connections. Voice and data solutions for EMS.
AB  - Communications used to be so simple-1) grab the radio, 2) push and talk. Now
      we're besieged by a confusing assortment of technology and terms-wideband,
      broadband, VoIP, RoIP, ect.- and a constand thrumming imperative to achieve and
      improve and perfect some mystical state of full interoperability. Frankly, it can
      all be a bit much. With this supplement, we hope to clarify you options. We
      examine the importance of broadband for EMS, with its potential for larger data
      "pipes" between the hospital and the field; advances in the promising
      technologies of Voice over IP and Radio over IP; and how some systems are
      improving their interconnectedness and resulting operations. The jargon can be
      overwhelming, but the ideas are worth understanding.

PMID- 18814751
TI  - Your ethical landmark.

PMID- 18814752
TI  - Fulfilling the ethics and jurisprudence requirements of licensure.

PMID- 18814753
TI  - How do I handle patient dental records?

PMID- 18814754
TI  - Can my assistant do that?

PMID- 18814755
TI  - Mandatory reporting for dentists.

PMID- 18814756
TI  - Called to serve: jury duty and medical review panels.

PMID- 18814757
TI  - Patient consent.

PMID- 18814758
TI  - Is your advertising ethical?

PMID- 18814759
TI  - The Americans with Disabilities Act: what you need to know.

PMID- 18814760
TI  - Do you know "Madison"?

PMID- 18814761
TI  - [Don't forget about heart disease in women].

PMID- 18814762
TI  - [What is the purpose of dual or triple inhibition of the renin-angiotensin
      aldosterone system?].
AB  - The blockade of the renin-angiotensin-aldosterone system (RAAS) is helpful in the
      management of arterial hypertension, congestive heart failure, post-myocardial
      infarction and diabetic nephropathy. Such blockade can be obtained with an
      angiotensin converting enzyme inhibitor, a specific antagonist of angiotensin II
      AT1 receptors, an aldosterone receptor antagonist and/or a direct inhibitor of
      renin such as aliskiren. Various studies have demonstrated that a dual or even
      triple RAAS inhibition may offer a better cardiorenal protection, in refractory
      congestive heart failure and in nephropathy with proteinuria. However, in the
      ONTARGET study, the dual inhibition with ramipril plus telmisartan did not
      provide any additional benefit compared to ramipril alone in high-risk
      cardiovascular patients, but showed a worse tolerance profile.

PMID- 18814763
TI  - [Therapeutic impact of screening for myocardial ischemia among asymptomatic type
      2 diabetic subjects].
AB  - Coronary artery disease is the major cause of mortality of type 2 diabetic
      subjects. Its early diagnosis to prevent progression and clinical events has
      intuitive appeal. Somehow, rationale for screening has not been clearly
      established. Screening should not modify the medical therapy because diabetic
      subjects have to be treated in a secondary prevention strategy. We have no data
      from randomized trials concerning a better outcome after revascularization in
      this specific population. The question how to select the high risk population to
      be screened has no response by now. SPECT and stress echocardiography seem
      valuable for screening but not for risk stratification. A large randomized
      clinical trial is required to confirm the cost-utility ratio of such a screening.

PMID- 18814764
TI  - [Coronary drug-eluting stents in diabetic patients].
AB  - In diabetic patients, the use of drug-eluting stents (paclitaxel-PES or sirolimus
      SES) reduces the risk of restenosis as compared to bare-metal stents. However,
      the risk of (very) late thrombosis is higher with drug-eluting stents than with
      bare-metal stents. All together, the incidence of major cardiovascular events is
      reduced with drug-eluting stents, mainly resulting from a diminution of
      revascularisation procedures rather than from a reduction in myocardial infarcts
      or cardiovascular deaths. Attempts to compare SES and PES gave discordant results
      in both randomised trials and registries. Efficacious antiplatelet therapy in the
      long run is mandatory in all diabetic patients treated with drug-eluting stents.

PMID- 18814765
TI  - [CB1 receptor inhibition and glucose metabolism: role of rimonabant in type 2
      diabetes].
AB  - Endocannabinoid system is overactivated in individuals with abdominal obesity.
      CBI receptors, first individualized in the brain, are also expressed in the
      adipocyte, the skeletal muscle, the liver, the gut, and the pancreas. Their
      blockade improves glucose tolerance and lipid profile, thanks increased insulin
      sensitivity and adiponectin levels. Rimonabant, a selective antagonist of CBI
      receptors, improves glucose control in patients with type 2 diabetes, treated
      with diet alone, metformin, sulfonylurea or insulin, while it also reduces body
      weight and other risk factors. Ongoing studies aim at further demonstrating the
      potential of rimonabant in the management of type 2 diabetes, in the prevention
      of type 2 diabetes and in the protection against cardiovascular complications in
      (diabetic) patients with abdominal obesity.

PMID- 18814766
TI  - [Clinical indications of radioimmunotherapy in lymphoma].
AB  - In their later stages low grade lymphoma are incurable. These lymphomas being
      radio-sensitive, a treatment of metabolic radioimmunotherapy, using monoclonal
      antibodies (anti-CD20) as the carrier has been developed. The aim of this
      treatment is to use these antibodies to target radiation to tumor tissues while
      limiting toxicity to normal cells. Ibritumomab tiuxetan (Zevalin) is currently
      prescribed for patients with relapsed or refractory low-grade follicular lymphoma
      after rituximab treatment. This outpatient treatment has a high level of overall
      response rate including complete response and that for a long period. The side
      effects are essentially hematological and reversible. In the near future many
      more indications should become apparent and Zevalin should become an important
      tool in the B-cell lymphoma (low and high grade).

PMID- 18814767
TI  - [Syphilis in 2008: practical aspects and controversies].
AB  - Rising incidence rate of syphilis is observed in economically advanced countries,
      particularly among homosexual men and subpopulation with low socioeconomic
      status. The various clinical presentations are divided into early and late
      stages, including neurosyphilis. The latter can occur during any stage of the
      disease, leading to the question "when to perform lumbar puncture", particularly
      in HIV positive patients. Penicillin continues to be the first-line therapy for
      all stages of syphilis. An alternative treatment should be considered as an
      exemption, after advice from a specialist. All patients require prolonged
      clinical and serological follow-up after treatment to rule out relapse or re
      infection. The diagnosis of syphilis is an opportunity to search and treat other
      sexually transmitted diseases in patients and their sexual partner(s).

PMID- 18814768
TI  - [Rimonabant helps in overweight patients with multiple cardiovascular risk
      factors such as type 2 diabetes].

PMID- 18814769
TI  - [Terrorist bomb attacks: injuries and response].

PMID- 18814770
TI  - [Public access defibrillation].
AB  - Placement of automated external defibrillators (AED) in public facilities and
      training of the lay persons in basic life support-defibrillation (BLS-D) was
      recommended by the American Heart Association for the treatment of out-of
      hospital cardiac arrest (OHCA). Immediate use of AED result in increase of
      survival to hospital discharge. Many observation and much less randomized trials
      describe clinical efficacy of this approach. However, "negative" trials have also
      been published and some recent data suggest that public access defibrillation
      (PAD) will have a minimal impact on population survival. In this article various
      PAD strategies were briefly reviewed. In our opinion installation of AED in
      public places should be based on the long-term study of local OHCA demography and
      preceded by widespread BLS training of lay population.

PMID- 18814771
TI  - [Definition of death and organ transplantation].

PMID- 18814772
TI  - [2008 and stem cells: corticogenesis].

PMID- 18814773
TI  - [United Nations report of HIV/AIDS epidemiology].

PMID- 18814774
TI  - [Cervical cancer vaccine: first French results].

PMID- 18814775
TI  - Cost of putting patients first: $0; professional credibility: priceless.

PMID- 18814776
TI  - Are extended show, venue change solutions to crowded Spring Session?

PMID- 18814777
TI  - Overfed but undernourished.

PMID- 18814778
TI  - Treatment planning: an art or a science?

PMID- 18814779
TI  - The influence of posterior occlusion when restoring anterior teeth.
AB  - When any type of esthetic restorative procedure is being considered or performed,
      a comprehensive diagnosis and treatment plan is required. Attention to the
      diagnostic signs of the loss of posterior support (LPS) and their influence on
      the anterior dentition will guarantee a more predictable outcome. Historical
      solutions and their inadequacies are addressed. Patient presentations are
      utilized to demonstrate contemporary treatment of patients requiring esthetic
      rehabilitations who are lacking posterior support.

PMID- 18814780
TI  - Multidisciplinary care: periodontal aspects to treatment planning the anterior
      esthetic zone.
AB  - The field of periodontology has changed dramatically during the past 30 years.
      The goal of periodontal therapy is not only to establish and maintain the
      dentition and the periodontium free of any oral infections, but also to provide
      an environment with optimal function and esthetics. Esthetics has become an
      integral portion of the overall treatment goal in periodontics. This article
      discusses the role of periodontal plastic and reconstructive surgery in treatment
      planning the anterior esthetic zone in interdisciplinary dental care.

PMID- 18814781
TI  - Integrating orthodontics for the optimal smile.
AB  - With the rapid and complex advancements in materials and technology in dentistry
      today, it has become difficult for the dental practitioner to stay current in one
      field, let alone more than one. In order to increase patient benefits and
      decrease the dentist's frustration, today's dental practice requires an
      interdisciplinary approach that integrates the knowledge, skills, and experience
      of all the disciplines of dentistry and its associated fields. This article
      highlights the advantage of an interdisciplinary treatment approach and how
      knowledge of basic orthodontic techniques can help in producing a more
      comprehensive treatment plan.

PMID- 18814782
TI  - Transitioning patients from teeth to implants utilizing fixed restorations.
AB  - The provisional phase of treatment can be the most challenging in implant
      dentistry. The choice of provisional restoration should be based on esthetic
      demands, functional requirements, duration, and ease of fabrication. One major
      obstacle to treatment with implants is the transitional phase between a tooth
      supported occlusion and an implant-supported occlusion. This is of particular
      concern when a patient with a failing dentition has not worn a removable
      prosthesis before and is planned to have a reconstruction supported by implants.

PMID- 18814784
TI  - Gold fever.

PMID- 18814783
TI  - The team approach: simplifying complex care.
AB  - In today's oral and maxillofacial surgery practice, the interaction between the
      oral and maxillofacial surgeon, the restorative dentist, and the rest of the
      dental and medical community is the foundation of daily patient care and
      management. The combination of the talents from each medical and dental
      discipline results in the highest quality of patient care. The following will
      illustrate the power of the comprehensive team approach.

PMID- 18814785
TI  - Health care ethics: changes on the way.

PMID- 18814786
TI  - Precision and certitude: laws governing laws.

PMID- 18814787
TI  - The future of evidence-based community benefit.

PMID- 18814788
TI  - Governance and management of community benefit.

PMID- 18814789
TI  - Using the dashboard technology properly.

PMID- 18814790
TI  - More than just numbers.

PMID- 18814791
TI  - Measuring the impact of community benefit.

PMID- 18814792
TI  - Incorporating quality assessment and improvement.

PMID- 18814793
TI  - Making multiple methods in evaluation work for Catholic hospitals.

PMID- 18814794
TI  - Explaining the new rules for measuring community benefit.

PMID- 18814795
TI  - From Idaho to Haiti: a medical mission story.

PMID- 18814796
TI  - Mission by the numbers.

PMID- 18814797
TI  - Spreading hope and faith to troubled women.

PMID- 18814798
TI  - [Clinical effects of biapenem on febrile neutropenia in patients with
      hematological malignancy].
AB  - BACKGROUND: Recent advances in the treatment of hematological malignancies often
      induce febrile neutropenia (FN) due to severe myelosuppression. The aim of this
      study was to evaluate the safety and efficacy of biapenem in such FN. METHODS:
      Candidate patients were admitted to our hospital and were treat of their
      hematological malignancy from February 2005 to March 2006. They gave written
      informed consent to enter this study in advance. When the diagnosis of FN was
      established among them, those patients received intravenous biapenem 0.6 g every
      12 hours. This trail was approved by our institutional review board. RESULTS: A
      total of 54 consecutive patients were registered and 49 patients were evaluable
      for response. The median age was 61. The underlying diseases were acute
      lymphocytic leukemia in 6 cases, acute myelocytic leukemia in 21, multiple
      myeloma in 3, and non-Hodgkin's lymphoma in 19. The response rate was 78%
      (excellent response: 51%, good response: 27%, minor response: 6%, no response:
      16%). In patients with neutrophil counts under 500/microl, the response rate was
      73%. Infectious death or other serious adverse events were not observed.
      CONCLUSION: Biapenem is effective and safe for treating FN.

PMID- 18814799
TI  - [Bacteria isolated from surgical infections and its susceptibilities to
      antimicrobial agents--special references to bacteria isolated between April 2006
      and March 2007].
AB  - Tendency of isolated bacteria from infections in abdominal surgery during the
      period from April 2006 to March 2007 were investigated in a multicenter study in
      Japan, and the following results were obtained. In this series, 474 strains
      including 23 strains of Candida spp. were isolated from 170 (75.2%) of 226
      patients with surgical infections. Two hundred and twenty-six strains were
      isolated from primary infections, and 224 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 Staphylococcus spp. was higher from postoperative
      infections, while Enterococcus spp. was higher from primary infections. Among
      aerobic Gram-negative bacteria, Escherichia coli was the most predominantly
      isolated from primary infections, followed by Klebsiella pneumoniae, Enterobacter
      cloacae and Pseudomonas aeruginosa, in this order, and from postoperative
      infections, P. aeruginosa was the most predominantly isolated, followed by E.
      coli and E. cloacae. Among anaerobic Gram-negative bacteria, the isolation rate
      of Bilophila wadsworthia was the highest from primary infections, followed by
      Bacteroides fragilis and from postoperative infections, B. fragilis was most
      predominately isolated, followed by Bacteroides caccae, Bacteroides
      thetaiotaomicron and B. wadsworthia in this order. In this series, we noticed no
      methicillin-resistant Staphylococcus aureus, nor multidrug-resistant P.
      aeruginosa. There were three strains of methicillin-resistant coagulase-negative
      Staphylococcus aureus, but all of them had good susceptibilities against various
      anti-MRSA antibiotics. We should carefully follow up B. wadsworthia.

PMID- 18814800
TI  - [PK/PD breakpoints and clinical/bacteriological effects of cefcapene pivoxil fine
      granules for children at free drug concentrations in pediatric patients with
      respiratory infection].
AB  - A post-marketing clinical study was previously conducted in pediatric patients
      with respiratory infection to evaluate the pharmacokinetics, efficacy and safety
      of cefcapene pivoxil (CFPN-PI) fine granules for children. Based on the results
      from this study, we evaluated PK/PD breakpoints and clinical/bacteriological
      effects of CFPN-PI at free drug concentrations in pediatric patients with
      respiratory infection to determine an effective and safe dosage regimen of CFPN
      PI. The following results were obtained from 61 pediatric patients evaluated in
      our research. 1) The response rate of pediatric respiratory infection to CFPN-PI
      was 100% for laryngopharyngitis, 84.6% for acute bronchitis, 100% for
      tonsillitis, 100% for pneumonia and 95.8% for all. 2) The bacteriological
      response (eradication rate of Haemophilus influenzae, Streptococcus pyogenes,
      Moraxella catarrhalis, Streptococcus pneumoniae, etc.) of pediatric respiratory
      infection to CFPN-PI was 87.5% for laryngopharyngitis, 66.7% for acute
      bronchitis, 75.0% for tonsillitis, 63.6% for pneumonia and 73.8% for all. 3) The
      blood concentration simulation demonstrated that the PK/PD breakpoint exceeding
      the time above MIC (TAM) of 40% after administration of CFPN-PI 3 mg/kg three
      times daily was 0.27 microg/mL. 4) The pediatric patients with respiratory
      infection were stratified by the TAM (%) of CFPN-PI into 40% to 100% (TAM > or =
      40% group) and 0% to 40% (TAM < 40% group) to compare the clinical and
      bacteriological effects of CFPN-PI. The clinical and bacteriological response
      rates, respectively, were 97.4% and 77.8% in the TAM > or = 40% group, and 88.9%
      and 62.5% in the TAM < 40% group. There was no difference in the clinical effect
      between the two TAM-stratified groups. On the other hand, the bacteriological
      effect, i.e., eradication rate, tended to be higher in the TAM > or = 40% group
      than in the TAM < 40% group, although the between-group difference was not
      statistically significant.

PMID- 18814801
TI  - [Search for microbial metabolites targeting apoptosis-control systems in tumor
      cells and their bioorganic chemistry].

PMID- 18814802
TI  - Effect of calcium salts of a mixture of conjugated linoleic acids containing
      trans-10, cis-12 in the diet on milk fat synthesis in goats.
AB  - Dietary supplements of conjugated linoleic acid (CLA) containing trans-10, cis-12
      CLA decrease milk fat secretion in the lactating cow and sheep, but their effects
      on mammary lipogenesis in the goat are less well defined. Eight lactating goats
      were used in two 4 x 4 Latin-square experiments with 14 d experimental periods to
      examine the effects of calcium salts of CLA methyl esters (CaCLA) containing
      trans-10, cis-12 on milk fat synthesis. Experimental treatments consisted of
      incremental inclusion of 0, 30, 60 or 90 g of CaCLA/d (corresponding to 7.47,
      14.9 and 22.4 g/d of trans-10, cis-12 CLA) offered during the first 10 d of each
      experimental period that replaced maize grain in concentrates (Experiment 1) or
      calcium salts of palm oil fatty acids (Experiment 2). Relative to the control,
      inclusion of 30, 60 or 90 g CaCLA/d in the diet reduced milk fat yield by 19.8,
      27.9 and 32.3 % and 17.5, 39.0 and 49.3 % in Experiments 1 and 2, respectively.
      Decreases in milk fat were due to reductions in the secretion of fatty acids
      synthesised de novo rather than the uptake of fatty acids from the peripheral
      circulation. Indirect comparisons with the studies in the lactating cow indicated
      a lower efficacy of CaCLA supplements on mammary lipogenesis in the goat. In
      conclusion, CaCLA in the diet inhibits milk fat synthesis in the goat, responses
      that are dependent on the supply of dietary fatty acids, with evidence that the
      caprine is less sensitive to the anti-lipogenic effects of trans-10, cis-12 CLA
      compared with the bovine or ovine.

PMID- 18814803
TI  - Prebiotics, immune function, infection and inflammation: a review of the
      evidence.
AB  - Beta2-1 fructans are carbohydrate molecules with prebiotic properties. Through
      resistance to digestion in the upper gastrointestinal tract, they reach the colon
      intact, where they selectively stimulate the growth and/or activity of beneficial
      members of the gut microbiota. Through this modification of the intestinal
      microbiota, and by additional mechanisms, beta2-1 fructans may have beneficial
      effects upon immune function, ability to combat infection, and inflammatory
      processes and conditions. In this paper, we have collated, summarised and
      evaluated studies investigating these areas. Twenty-one studies in laboratory
      animals suggest that some aspects of innate and adaptive immunity of the gut and
      the systemic immune systems are modified by beta2-1 fructans. In man, two studies
      in children and nine studies in adults indicate that the adaptive immune system
      may be modified by beta2-1 fructans. Thirteen studies in animal models of
      intestinal infections conclude a beneficial effect of beta2-1 fructans. Ten
      trials involving infants and children have mostly reported benefits on infectious
      outcomes; in fifteen adult trials, little effect was generally seen, although in
      specific situations, certain beta2-1 fructans may be beneficial. Ten studies in
      animal models show benefit of beta2-1 fructans with regard to intestinal
      inflammation. Human studies report some benefits regarding inflammatory bowel
      disease (four positive studies) and atopic dermatitis (one positive study), but
      findings in irritable bowel syndrome are inconsistent. Therefore, overall the
      results indicate that beta2-1 fructans are able to modulate some aspects of
      immune function, to improve the host's ability to respond successfully to certain
      intestinal infections, and to modify some inflammatory conditions.

PMID- 18814804
TI  - Effects of oral fat perception by modified sham feeding on energy expenditure,
      hormones and appetite profile in the postprandial state.
AB  - Previously, we have shown that satiety and metabolites increased after high-fat
      modified sham feeding (MSF). We assessed possible metabolic effects due to oral
      stimulation with a high-fat sham-fed 'meal', in comparison with a high-fat fed
      meal and with water, in the postprandial state. Fourteen healthy women (aged 18
      40 years; BMI 22.5 (SD 3) kg/m2) were fed in energy balance during 4 d with a 50
      % energy as carbohydrate, 15 % energy as protein and 35 % energy as fat menu. On
      day 4, subjects were given one out of three test lunches, 5 h after a high-fat
      breakfast, in random order: a high-fat MSF lunch, water (W) or the same lunch to
      be eaten (E), during their 36 h stay in the respiration chamber, where substrate
      oxidation, 24 h energy expenditure (EE) and appetite profile were measured. Oral
      fat stimulation by MSF increased EE (W 6.3 (SD 0.8) v. MSF 6.9 (SD 1.0) kJ/min
      and E 6.8 (SD 0.7) kJ/min; P < 0.04) for 1 h, increased plasma insulin
      concentrations (t = 15; W 10.0 (SD 3.4) v. MSF 13.2 (SD 4.0) v. E 22.3 (SD 3.3)
      units/l; P < 0.0001), attenuated changes in plasma NEFA concentrations (t = 15, W
      432 (SD 108) v. MSF 418 (SD 146) v. E 282 (SD 72) micromol/l; P < 0.0001), plasma
      TAG concentrations (t = 60; W 1092 (SD 548) v. MSF 1116 (SD 493) micromol/l and E
      1350 (SD 352) micromol/l; P < 0.02) and plasma glycerol concentrations (t = 15, W
      87 (SD 29) v. MSF 74 (SD 34) micromol/l and E 67 (SD 18) micromol/l; P < 0.03).
      Over a longer period of time, MSF had no effects on substrate oxidation, diet
      induced thermogenesis or total EE. In addition to the previously observed
      metabolic effects of oral stimulation with fat, EE is stimulated up to 1 h after
      the MSF meal.

PMID- 18814805
TI  - Glycaemic index database for the epidemiological Alpha-Tocopherol, Beta-Carotene
      Cancer Prevention (ATBC) Study.
AB  - Interest in the dietary glycaemic index (GI) and glycaemic load (GL) as risk
      factors for chronic diseases has grown in recent years but findings have been
      controversial. We describe the compilation of the GI database for the cohort
      studies within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study
      and the main characteristics associating with diet GI and GL. The ATBC Study
      enrolled 29 133 male smokers aged 50-69 years who filled in a dietary history
      questionnaire upon study entry. The dietary data included 1097 foods, of which
      195 foods with no or a negligible amount of available carbohydrates were assigned
      a GI of zero. Based on preset methodological criteria for published GI studies,
      the GI value of a similar food was available for 130 foods, and the GI of related
      food was assigned to 360 foods. The GI values of these foods served in the GI
      calculation of 412 composite foods. The median diet GI among the ATBC Study
      participants was 67.3 (interquartile range 64.8-70.0), and the median diet GL was
      175 (interquartile range 158-192). The intakes of carbohydrates, protein and fat
      decreased, and the intake of fibre increased, with increasing GI. The GL showed a
      positive correlation with intakes of carbohydrates and dietary fibre and a
      negative correlation with intakes of protein and fat. The GI studies available
      that fulfilled the minimum methodological requirements cover a sufficient amount
      of foods to form a meaningful GI database for epidemiological study. This,
      however, requires the availability of GI values for relevant local carbohydrate
      containing foods.

PMID- 18814806
TI  - Psychosocial treatments of behavior symptoms in dementia: a systematic review of
      reports meeting quality standards.
AB  - OBJECTIVE: To provide a systematic review of selected experimental studies of
      psychosocial treatments of behavioral disturbances in dementia. Psychosocial
      treatments are defined here as strategies derived from one of three
      psychologically oriented paradigms (learning theory, unmet needs and altered
      stress thresholds). METHOD: English language reports published or in press by
      December 2006 were identified by means of database searches, checks of previous
      reviews and contact with recognized experts. Papers were appraised with respect
      to study design, participants' characteristics and reporting details. Because
      people with dementia often respond positively to personal contact, studies were
      included only if control conditions entailed similar levels of social attention
      or if one treatment was compared with another. RESULTS: Only 25 of 118 relevant
      studies met every specification. Treatment proved more effective than an
      attention control condition in reducing behavioral symptoms in only 11 of the 25
      studies. Effect sizes were mostly small or moderate. Treatments with moderate or
      large effect sizes included aromatherapy, ability-focused carer education, bed
      baths, preferred music and muscle relaxation training. CONCLUSIONS: Some
      psychosocial interventions appear to have specific therapeutic properties, over
      and above those due to the benefits of participating in a clinical trial. Their
      effects were mostly small to moderate with a short duration of action. This
      limited action means that treatments will work best in specific, time-limited
      situations. In the few studies that addressed within-group differences, there
      were marked variations in response. Some participants benefited greatly from a
      treatment, while others did not. Interventions proved more effective when
      tailored to individuals' preferences.

PMID- 18814807
TI  - The relationship of excess cognitive impairment in MCI and early Alzheimer's
      disease to the subsequent emergence of psychosis.
AB  - BACKGROUND: Psychotic symptoms in Alzheimer disease (AD + P) identify a heritable
      phenotype associated with greater cognitive impairment. Knowing when the
      cognitive course of AD + P subjects diverges from that of subjects without
      psychosis would enhance understanding of how genetic variation results in AD + P
      and its associated cognitive burden. This study seeks to determine whether the
      degree of cognitive impairment and cognitive decline in early AD predicts
      subsequent AD + P onset. METHODS: 361 subjects with possible or probable AD or
      mild cognitive impairment (MCI) without psychosis were evaluated every 6 months
      until psychosis onset. RESULTS: Severity of cognitive dysfunction was a strong
      predictor of AD + P up to two years prior to psychosis onset. Cognition did not
      decline more rapidly prior to onset of AD + P. CONCLUSIONS: Individuals who will
      develop AD + P already demonstrate excess cognitive impairment during the mild
      stages of disease. Genetic variation and brain pathophysiology may lead to a
      cognitive risk phenotype which is present prior to dementia onset.

PMID- 18814808
TI  - The effects of social structure and sex-biased transmission on macroparasite
      infection.
AB  - Mathematical models of disease dynamics tend to assume that individuals within a
      population mix at random and so transmission is random, and yet, in reality
      social structure creates heterogeneous contact patterns. We investigated the
      effect of heterogeneity in host contact patterns on potential macroparasite
      transmission by first quantifying the level of assortativity in a socially
      structured wild rodent population (Apodemus flavicollis) with respect to the
      directly-transmitted macroparasitic helminth, Heligmosomoides polygyrus. We found
      the population to be disassortatively mixed (i.e. male mice mixing with female
      mice more often than same sex mixing) at a constant level over time. The
      macroparasite H. polygyrus has previously been shown to exhibit male-biased
      transmission so we used a Susceptible-Infected (SI) mathematical model to
      simulate the effect of increasing strengths of male-biased transmission on the
      prevalence of the macroparasite using empirically-derived transmission networks.
      When transmission was equal between the sexes the model predicted macroparasite
      prevalence to be 73% and infection was male biased (82% of infection in the male
      mice). With a male-bias in transmission ten times that of the females, the
      expected macroparasite prevalence was 50% and was equally prevalent in both
      sexes, results that both most closely resembled empirical dynamics. As such,
      disassortative mixing alone did not produce macroparasite dynamics analogous to
      those from empirical observations; a strong male-bias in transmission was also
      required. We discuss the relevance of our results in the context of network
      models for transmission dynamics and control.

PMID- 18814809
TI  - Invention, innovation, and evocation.

PMID- 18814810
TI  - Perfecting nerve-sparing radical prostatectomy: sailing in uncharted waters.

PMID- 18814811
TI  - Development of a near-infrared spectroscopy instrument for applications in
      urology.
AB  - INTRODUCTION: Near infrared spectroscopy (NIRS) is an established technology
      using photons of light in the near infrared spectrum to monitor changes in tissue
      of naturally occurring chromophores, including oxygenated and deoxygenated
      hemoglobin. Technology and methodology have been validated for measurement of a
      range of physiologic parameters. NIRS has been applied successfully in urology
      research; however current instruments are designed principally for brain and
      muscle study. OBJECTIVE: To describe development of a NIRS instrument
      specifically designed for monitoring changes in chromophore concentration in the
      bladder detrusor in real time, to facilitate research to establish the role of
      this non-invasive technology in the evaluation of patients with voiding
      dysfunction METHOD: The portable continuous wave NIRS instrument has a 3 laser
      diode light source (785, 808 and 830 nanometers), fiber optic cables for light
      transmission, a self adhesive patient interface patch with an emitter and sensor,
      and software to detect the difference between the light transmitted and received
      by the instrument. Software incorporated auto-attenuates the optical signals and
      converts raw optical data into chromophore concentrations displayed graphically.
      RESULTS: The prototype was designed, tested, and iteratively developed to achieve
      optimal suprapubic transcutaneous monitoring of the detrusor in human subjects
      during bladder filling and emptying. Evaluation with simultaneous invasive
      urodynamic measurement in men and women indicates good specificity and
      sensitivity of NIRS chromophore concentration changes by receiver operator curve
      analysis, and correlation between NIRS data and urodynamic pressures. CONCLUSION:
      Urological monitoring with this NIRS instrument is feasible and generates data of
      potential diagnostic value.

PMID- 18814812
TI  - Near-infrared spectroscopy: validation of bladder-outlet obstruction assessment
      using non-invasive parameters.
AB  - INTRODUCTION: Near infrared spectroscopy (NIRS) is a non-invasive optical
      technique able to monitor changes in the concentration of oxygenated and
      deoxygenated hemoglobin in the bladder detrusor during bladder filling and
      emptying. OBJECTIVE: To evaluate the ability of a new NIRS instrument and
      algorithm to classify male patients with LUTS as obstructed or unobstructed based
      on comparison with classification via conventional invasive urodynamics (UDS).
      METHOD: Male patients with LUTS were recruited and underwent uroflow and
      urodynamic pressure flow studies with simultaneous transcutaneous NIRS monitoring
      following measurement of post residual volume (PVR) via ultrasound. Data analysis
      first classified each subject as obstructed or unobstructed using the standard
      pressure flow data and nomogram, then compared these results with a
      classification derived via a customized algorithm which analyzed the pattern of
      change of the NIRS data plus measurements of PVR and Qmax. RESULTS: Seventy
      subjects enrolled: 57 data sets had all required parameters [13 incomplete sets
      due to: communication error between NIRS and urodynamics instruments (9); data
      saving error (1); damaged fiber optic cables (3)]. Two complete data sets were
      excluded [subjects with hematuria (2)]. Thus data from 55 subjects was analyzed.
      The NIRS algorithm correctly identified those diagnosed as obstructed by
      conventional urodynamic classification in 24 of 28 subjects (sensitivity =
      85.71%) and, and those diagnosed as unobstructed in 24 of 27 subjects
      (specificity = 88.89%). CONCLUSION: Scores derived from NIRS data plus PVR and
      Qmax are able to correctly identify > 85% of subjects classified as obstructed
      using UDS.

PMID- 18814813
TI  - Prevalence and predictive factors for the development of de novo psychiatric
      illness in patients receiving androgen deprivation therapy for prostate cancer.
AB  - OBJECTIVE: Androgen deprivation therapy (ADT) remains a widely utilized modality
      for treatment of localized and advanced prostate cancer. While ADT-induced
      alterations in testosterone have demonstrated impacts on quality of life, the
      effects on mental health remain ill-defined. We investigated the prevalence of de
      novo psychiatric illness and predictive factors following ADT induction for
      prostate cancer. MATERIALS AND METHODS: We retrospectively reviewed patients
      receiving ADT for prostate cancer at our institution between 1/1989-7/2005,
      excluding men receiving only neoadjuvant ADT. Variables included age, race, body
      mass index, prostate-specific antigen (PSA), Gleason sum, clinical stage, ADT
      type (medical/surgical) and schedule (continuous/intermittent), and presence of
      pre-ADT and newly diagnosed psychiatric illness. The cohort was divided into
      three groups for analysis: pre-ADT psychiatric illness, de novo psychiatric
      illness, and no psychiatric illness. Data analysis utilized statistical software
      with p < 0.05 considered significant. RESULTS: Three-hundred and ninety-five
      patients with a mean age of 71.7 years at ADT initiation were analyzed. Thirty
      four men (8.6%) were diagnosed with pre-ADT psychiatric illness. At mean follow
      up of 87.4 months, 101 (27.9%) men were diagnosed with de novo psychiatric
      illness, most commonly including: depression (n = 57; 56.4%), dementia (n = 14;
      13.9%), and anxiety (n = 9; 8.9%). On multivariate analysis, increasing pre-ADT
      PSA was predictive of post-ADT anxiety (p = 0.01). Overall and disease-specific
      survival outcomes were similar between groups. CONCLUSIONS: De novo psychiatric
      illness was identified in 27.9% of men. While no predictive factors were
      identified for de novo psychiatric illness, increasing PSA was associated with de
      novo anxiety. Prospective investigation using validated instruments is requisite
      to further delineate the relationship between ADT and psychiatric health.

PMID- 18814815
TI  - The prognostic value of vascular endothelial growth factor (VEGF)-A and its
      receptor in clinically localized prostate cancer: a prospective evaluation in 100
      patients undergoing radical prostatectomy.
AB  - OBJECTIVES: To study the prognostic value of vascular endothelial growth factor
      (VEGF)-A and its receptor VEGFR-1 in localized prostate cancer. METHODS: One
      hundred patients undergoing radical prostatectomy (RP) for clinically localized
      prostate cancer were prospectively included. Plasma levels of VEGF-A were
      measured preoperatively. After intervention, tissue microarrays were built from
      the RP specimens. VEGF-A and VEGFR-1 expressions in prostate cancer tissue were
      determined using immunochemistry. Then the associations between plasma levels of
      VEGF-A, VEGF-A and VEGFR-1 expressions in prostate cancer tissue, and the outcome
      of patients were analyzed. RESULTS: After a median follow-up of 22 months, 14
      patients experienced biological recurrence of prostate cancer. There was no
      correlation between plasma VEGF-A and the risk of recurrence following RP.
      Moreover, there was no correlation between VEGF-A expression or VEGFR-1
      expression in prostate cancer tissue and the risk of recurrence after RP.
      CONCLUSIONS: Plasma levels of VEGF-A, the expression of VEGF-A and that of VEGFR
      1 in prostate cancer tissue did not affect patients outcome following RP. VEGF-A
      and its receptor VEGFR-1 may have no prognostic value in localized prostate
      cancer. Further studies with longer follow-up are mandatory to confirm these
      findings.

PMID- 18814816
TI  - Robotic radical prostatectomy in patients with preexisting inflatable penile
      prosthesis (IPP).
AB  - PURPOSE: We present our initial experience with performing robotic-assisted
      prostatectomies in men with a 3-piece inflatable penile prosthesis with a pelvic
      reservoir. MATERIAL AND METHODS: Four patients underwent transperitoneal robotic
      assisted radical prostatectomies with a penile prosthetic implant in place. The
      reservoir was left inflated for easy identification. A flaccid reservoir may be
      more difficult to identify, and be prone to damage. The reservoir was left
      attached to the abdominal wall. Dissection was performed outside the fibrous
      capsule of the reservoir. The tissue around the capsule of the reservoir peeled
      off without difficulty. Cutting current close to the capsule can be used if
      needed as per American Medical System with no limit to voltage. The penile
      prosthesis is then inflated to empty the reservoir creating more prevesical space
      and preventing the reservoir from obscuring visualization. The remaining portion
      of the procedure is completed using our standard technique. After completing the
      urethrovesical anastomosis using the 16 French Foley, the prosthesis is cycled
      under direct vision and the penile prosthesis is deflated (reservoir full). The
      prosthesis is not used for 6 weeks to prevent stretching of the urethrovesical
      anastomosis. RESULTS: All patients (n = 4) had no reported complications and all
      prostheses are functioning properly. The margin status was negative
      postoperatively. CONCLUSION: Robotic prostatectomy is technically feasible in
      patients with inflatable penile prostheses by surgeons experienced in robotic
      surgery. However, the presence of an indwelling penile prosthesis does increase
      the complexity of surgery.

PMID- 18814817
TI  - Signet-ring cell carcinoma arising from the urinary bladder.
AB  - INTRODUCTION: Signet-ring cell carcinoma of the urinary bladder can be primary -
      arising from the bladder wall or urachus remnants - or metastatic from tumors
      originating in the stomach, colon, or breast. Saphir first described primary
      signet-ring cell cancer of the urinary bladder in 1955. Less than 100 cases have
      been reported in the literature since then. CASE REPORT: We report a case of a 45
      year-old woman who was admitted with gross hematuria. Cystoscopy revealed a
      necrotic tumor on the left bladder wall. A transurethral biopsy showed signet
      ring cell carcinoma. The bladder tumor was diagnosed as the primary one. Radical
      cystectomy was performed with ureterosigmoidostomy (Mainz pouch II). Histological
      examination showed a primary signet-ring cell carcinoma of the bladder
      (pT3bN0M0). Following surgery, the patient received adjuvant chemotherapy with
      cisplatin and fluorouracil. CONCLUSIONS: Primary signet-ring cell carcinoma of
      the urinary bladder is an extremely rare tumor, accounting for approximately
      0.24% of all bladder malignances. Patients with this type of cancer generally
      have a poor prognosis. However, our patient is free of disease 5 years after
      radical cystectomy.

PMID- 18814818
TI  - Vesicoenteric, vesicovaginal, vesicocutaneous fistula -an unusual complication
      with intravesical mitomycin.
AB  - Intravesical instillation of mitomycin C is a routine practice for treatment of
      superficial transitional cell carcinoma of bladder. Despite usual precautions
      serious side effects like fistulation can occur with diverse presentation as
      illustrated by this report. The pathology demonstrates a dense necrotic and
      massive inflammatory reaction in the peri vesical tissue following the
      extravasation of an intravesically administered chemotherapeutic agent. The
      severe inflammatory tissue response and the necrotic effect associated with the
      extravasated chemotherapeutic agent could potentially lead to local sepsis with a
      subsequent fistula formation.

PMID- 18814819
TI  - Delayed presentation of iliopsoas abscess from ureterosigmoidostomy stump
      fistulization 30 years following nephrectomy.
AB  - Although rarely used today for supravesical urinary diversion,
      ureterosigmoidostomy was commonly utilized in patients with bladder exstrophy. We
      report an unusual case of iliopsoas abscess developing 30 years after an
      ipsilateral nephrectomy in a patient with bladder exstrophy who had undergone
      ureterosigmoidostomy for urinary diversion more than 50 years prior. The etiology
      appeared to be persistent ureteral reflux and fistulization from a patent
      ureterosigmoidostomy stump. After percutaneous drainage of the abscess and
      intravenous antibiotic therapy, the patient was managed with complete excision of
      the ureterosigmoid anastomoses and creation of an ileal conduit urinary
      diversion.

PMID- 18814820
TI  - Chromophobe renal cell carcinoma presenting as hemorrhagic shock: case report.
AB  - The majority of patients with chromophobe renal cell carcinoma (CRCC) are
      determined to be asymptomatic, with a small minority of patients having the
      classic triad of flank pain, hematuria, and abdominal mass. This case report
      describes a 56-year-old man first seen with hemorrhagic shock from
      retroperitoneal bleeding attributable to a large renal mass. An emergent
      exploratory laparotomy and radical nephrectomy were performed and the patient has
      since remained disease free at 3 year follow-up.

PMID- 18814821
TI  - Office based non-oncology urology trials.

PMID- 18814822
TI  - Open clinical uro-oncology trials in Canada.

PMID- 18814823
TI  - North Central Section of the American Urological Association 82nd Annual Meeting,
      September 24-27, 2008, Chicago, Illinois, USA. Abstracts.

PMID- 18814824
TI  - Review of the pharmaceutical properties and clinical effects of the topical NSAID
      formulation, diclofenac epolamine.
AB  - BACKGROUND: Topical formulations of non-steroidal anti-inflammatory drugs
      (NSAIDs), in particular diclofenac (DI), have become popular for treating various
      acute and chronic painful inflammatory conditions. OBJECTIVE: To perform a
      literature review of (1) the use of topical NSAIDs; (2) the pharmaceutical,
      pharmacokinetic and pharmacodynamic properties of a medicated plaster (patch)
      containing diclofenac epolamine (DI-EP, Flector Tissugel, Flector patch) compared
      with other formulations of topical NSAIDs; and (3) evaluation of the clinical
      findings from studies with this novel DI-EP patch. OUTCOMES: (1) Pharmacokinetic
      studies involved determination of DI from DI-EP and separately epolamine (EP) and
      the epoxide metabolite (N-oxide-EP) in laboratory animals and humans; the latter
      being the major metabolite in humans. About 2% of DI is absorbed by the skin in
      humans and is excreted in the urine. Maximum plasma concentrations of 17.4 ng/mL
      DI are reached at 5.4 hours (approximate steady state conditions); the plasma
      elimination half-time (t(1/2)) being 26.4 hours. Low systemic levels of DI and EP
      are produced from DI-EP. Pronounced accumulation of DI occurs in the muscle
      layers and in synovial fluids of arthritic patients; (2) No significant toxicity
      occurs from EP nor N-oxide-EP, while that of oral DI-EP was similar to that from
      DI; and (3) In acute musculoskeletal conditions (sprains, tendonitis and sports
      injuries) and osteoarthritis DI-EP patches control pain and signs of joint or
      physical injury compared with placebo controls by 3-5 days with almost complete
      pain relief at 14 days. DI-EP was shown to have equivalent therapeutic effect to
      another DI diethylammonium gel formulation (Voltaren Emulgel). There were no
      reports of serious adverse events in the gastro-intestinal (GI) tract, kidneys or
      liver from DI-EP. Mild GI symptoms and skin reactions occur in 2 and 10% of
      patients, respectively. CONCLUSIONS: The patch delivery of DI in DI-EP affords
      controlled delivery of the active drug in contrast to that from application of
      gels or ointments of NSAIDs.

PMID- 18814825
TI  - Cost-effectiveness of venous thromboembolism prophylaxis in total hip and knee
      replacement surgery: the evolving application of health economic modelling over
      20 years.
AB  - OBJECTIVES: In the last two decades, there has been considerable evolution of
      methods for cost-effectiveness modelling. Some of the first models were developed
      in the area of venous thromboembolism (VTE) prophylaxis. Hence, this area can
      serve as an important example to illustrate evolving standards. Our objectives
      are to document evolving methodology by describing VTE models, assess their
      critical strengths and weaknesses, and inform future advances for models in this
      therapeutic area. RESEARCH DESIGN AND METHODS: A systematic review of economic
      models of primary VTE prevention following hip and knee replacement surgery was
      undertaken. Electronic searches of PubMed, EMBASE, the Cochrane library, and grey
      literature were conducted (1985-2006). Reference lists of included articles and
      reviews were examined for relevant studies. RESULTS: Twenty-nine cost
      effectiveness models were identified. Nineteen other cost-effectiveness analyses
      were excluded because they were not model-based; 16 were simple cost calculations
      and three were analyses of resource use data collected alongside clinical trials.
      The majority of models (24) were constructed as decision trees, frequently
      utilising previously published model structures, with some adaptation for new
      comparators, and/or addition of relevant events omitted by earlier models (e.g.,
      bleeding due to prophylactic treatment). Later models have included Markov
      processes to model potential long-term consequences of VTE (recurrent VTE and
      post-thrombotic syndrome) over longer time horizons. Systematic identification of
      clinical evidence and more sophisticated analysis methods (e.g., Bayesian mixed
      treatment comparisons and probabilistic sensitivity analyses) have recently been
      introduced. CONCLUSIONS: Model structures have evolved substantially in this
      highly studied therapeutic area, with improvements made to the model structure,
      the comprehensiveness of clinical evidence included, and the underlying
      calculation methodology.

PMID- 18814826
TI  - Therapeutic implications of implantable device-based monitoring of patients with
      heart failure.
AB  - Heart failure is one of the most common medical problems faced by patients and
      clinicians. It has the potential for high morbidity and mortality, and its
      overall financial cost to society is enormous. Management of heart failure is
      often difficult and time consuming, and is sometimes frustrating. The usual signs
      and symptoms of heart failure may not be obvious early in an exacerbation, which
      has prompted the development of other methods to identify early and subtle
      clinical changes to initiate early intervention. Current implantable devices,
      such as defibrillators and pacemakers, can monitor changes in heart rate and
      heart rate variability, patient activity, arrhythmia frequency, and thoracic
      impedance, all of which may be markers of clinical decline. Newer implantable
      devices can also measure right ventricular pressures, oxygen saturation, and
      pulmonary artery pressures. Many of these technologies have been shown to be
      feasible and potentially helpful, but outcomes data showing reductions in
      morbidity and mortality are currently limited. Importantly, none of these newer
      technologies should be used in isolation; all must be used in combination with
      clinical findings to provide effective disease management.

PMID- 18814827
TI  - Management of infections involving implanted cardiac electrophysiologic devices.
AB  - Indications for cardiac electrophysiologic device implantation have expanded, and
      the target demographic has widened. Unfortunately, these changes have been
      accompanied by an increase in cardiac device-associated infections out of
      proportion to the increase in implantation rate. Diagnosing a cardiac device
      infection may be challenging because of the spectrum of clinical manifestations,
      ranging from isolated generator pocket pain to frank sepsis with clear evidence
      of endocarditis. Any component of the device may be involved, but the cornerstone
      of therapy remains extraction of the device and its leads along with appropriate
      antibiotic treatment. Given the inherent risks of lead extraction, making the
      correct diagnosis is paramount. This review outlines the epidemiology,
      pathophysiology, clinical manifestations, diagnosis, and management of cardiac
      device infections.

PMID- 18814828
TI  - New developments in anticoagulation for atrial fibrillation.
AB  - The incidence of stroke in patients with atrial fibrillation (AF) is five times
      greater than that in age-matched controls. Warfarin reduces this incidence by two
      thirds and is the most effective agent for this indication. However, despite its
      efficacy, warfarin management is tedious and is useful only in a subsegment of
      the population who needs anticoagulation and has no contraindications. Many
      agents are poised to replace warfarin as an effective anticoagulant for stroke
      prevention in AF. The direct thrombin inhibitor dabigatran is furthest along in
      clinical development, followed by the factor Xa inhibitors rivaroxaban and
      apixaban. All these agents seem effective, and none appears mechanistically
      superior over another. Dabigatran's advantage is that it was tested in two
      dosages in a phase 3 evaluation based on earlier phase 2 studies in patients with
      AF, whereas dosage data for the other agents were extrapolated from phase 2
      programs for venous thromboembolism prevention. The vitamin K antagonist ATI-5923
      offers clinical benefits similar to warfarin's, but with no or fewer drug-drug
      interactions, potentially greater time in therapeutic range, and probably less
      need for dose adjustment and laboratory monitoring. It challenges the newer
      mechanistic agents in efficacy and raises the bar for comparison in future head
      to-head trials. Further analysis and clinical trial testing are still needed to
      determine whether one or all of these agents are effective anticoagulants for
      stroke prevention in patients with AF.

PMID- 18814829
TI  - Omega-3 fatty acid supplementation for the prevention of arrhythmias.
AB  - Fish oil, or omega-3 (n-3) polyunsaturated fatty acid (PUFA), supplements have
      been purported to produce potential health benefits. One of the strongest
      supported effects of n-3 PUFAs may be their potential benefits in reducing the
      risk of sudden cardiac death. This article reviews clinical and mechanistic
      studies that may explain the effects of these agents on ischemic arrhythmias,
      sudden death, and atrial fibrillation.

PMID- 18814830
TI  - Optimal Programming of ICDs for Prevention of Appropriate and Inappropriate
      Shocks.
AB  - Expansion of indications for implantable cardioverter-defibrillators (ICDs) has
      led to a significant increase in the number of patients receiving ICDs and the
      number of lives saved because of ICD therapy. However, appropriate or
      inappropriate shocks are frequent and may result in a significant decrease in
      quality of life in patients with ICDs. Atrial fibrillation with rapid ventricular
      response, sinus tachycardia, atrial tachycardia or atrial flutter with rapid
      conduction, and other supraventricular tachycardias are the most common
      arrhythmias causing inappropriate therapy. Other causes include oversensing of
      diaphragmatic potentials or myopotentials, T-wave oversensing, double or triple
      counting of intracardiac signals, lead fractures or header connection problems,
      lead chatter or noise, and electromagnetic interference. Strategies to reduce
      inappropriate therapy using device programming rely on the ability to distinguish
      supraventricular and atrial arrhythmias from ventricular tachycardia. Avoiding
      therapy for nonsustained ventricular arrhythmias and increasing the role of
      antitachycardia pacing to terminate ventricular tachycardia are key approaches to
      reducing shocks for ventricular arrhythmias. Optimal programming holds great
      promise for decreasing the overall incidence of shock therapy and increasing ICD
      acceptance.

PMID- 18814831
TI  - Cardiac MRI in the management of congenital heart disease in children,
      adolescents, and young adults.
AB  - Recent advances in MRI have made this modality an important tool for evaluating
      heart disease. Faster scanning techniques, high spatial resolution, lack of
      ionizing radiation, lack of dependence on contrast material, and capability for
      functional imaging have made it an emerging noninvasive diagnostic tool with
      great potential in younger patients with heart disease. This article discusses
      the role of cardiac MRI, methods of evaluation, and newer application of MRI in
      evaluating congenital heart disease in pediatric and young adult patients.

PMID- 18814832
TI  - CT in the evaluation of congenital heart disease in children, adolescents, and
      young adults.
AB  - Recent advances in multidetector CT have made this modality an important part of
      congenital heart disease (CHD) evaluation in young patients. Faster scanning
      techniques combined with improved spatial resolution allow for exquisite
      postprocessing, enabling accurate preoperative and postoperative anatomic
      depiction. To optimize this technique, one must have a structured approach to the
      patient with CHD.

PMID- 18814833
TI  - Therapeutic options in hypertrophic cardiomyopathy: a pediatric perspective.
AB  - Hypertrophic cardiomyopathy (HCM) is the most prevalent genetic cardiomyopathy in
      children and young adults. Despite advances in understanding the molecular
      etiology of this disorder, the clinical phenotypes vary widely from asymptomatic
      septal hypertrophy, to frank congestive heart failure due to left ventricular
      outflow tract obstruction (LVOTO), to unexpected sudden cardiac death. Thus,
      isolating a specific genetic defect in this disease does little to predict the
      clinical consequence. This is best seen in large families with several people
      affected by HCM who all have the identical mutation but who may have very
      different clinical phenotypes. Evaluating individuals with HCM consists of
      establishing the diagnosis through cardiac imaging, noninvasively assessing the
      risk for sudden death, and medically or surgically treating symptomatic LVOTO
      when it is present.

PMID- 18814834
TI  - Ventricular arrhythmia in children: diagnosis and management.
AB  - With increasing awareness of genetic abnormalities and the aging of patients with
      structural cardiac disease, particularly those who have had cardiac surgery,
      primary ventricular tachycardia is being recognized more frequently in children
      and adolescents and is becoming a larger management issue. The distinction of
      primary versus secondary is based on whether ventricular tachycardia is the
      inciting arrhythmia or the end result of a prolonged ischemic event, such as
      prolonged bradycardia with resultant ventricular tachycardia. This article
      discusses only primary ventricular tachycardia. The incidence clearly increases
      with age after cardiac surgery, particularly in specific cardiac abnormalities,
      such as tetralogy of Fallot post repair, transposition of the great arteries,
      post atrial switch operation, and hypertrophic obstructive cardiomyopathy. In
      addition, as genetic abnormalities are becoming better appreciated, conditions
      such as long QT syndrome, arrhythmogenic right ventricular cardiomyopathy, and
      Brugada syndrome, with their risk for ventricular tachycardia and fibrillation,
      are being seen increasingly in the pediatric population. Long-term treatment of
      ventricular tachycardia includes drug therapy, implantable device therapy,
      invasive ablation therapy, and combinations of these modalities. To choose the
      appropriate therapy, the clinician must consider the arrhythmia's effect on the
      patient's hemodynamic status and the potential for sudden cardiac death.

PMID- 18814835
TI  - Double-outlet left ventricle: diagnosis and management.
AB  - Double-outlet left ventricle (DOLV) is a rare congenital cardiac malformation in
      which both great arteries originate entirely or predominantly from the
      morphologic left ventricle. DOLV occurs most commonly in the form of atrial situs
      solitus with atrioventricular (AV) concordance. Ventricular septal defect (VSD)
      is most commonly subaortic, and 90% of these patients have associated pulmonary
      stenosis. In most cases, there is a right anterior position of the aorta relative
      to the pulmonary artery. Most patients with DOLV will have pulmonary outflow
      obstruction and present soon after birth with cyanosis. DOLV with two well
      developed ventricles is conventionally treated surgically by VSD closure, closure
      of the native left ventricle-to-pulmonary outflow, and placement of a right
      ventricle-to-pulmonary artery extracardiac conduit. However, pulmonary root
      translocation may be used as an alternative to biventricular repair of DOLV.
      Patients with DOLV and functionally single-ventricle or AV valve atresia will
      require a Fontan procedure.

PMID- 18814836
TI  - Development of an indirect method for measuring porcine pancreatic lipase in
      human duodenal fluid.
AB  - Patients with exocrine pancreatic insufficiency are usually treated with porcine
      pancreatic enzymes but the bioavailability of these enzymes in the gut remains a
      matter of discussion. In order to determine the duodenal availability of porcine
      pancreatic lipase (PPL) present in pancreatic extracts (PE) taken orally, we
      developed a method for quantifying PPL in samples containing both PPL and human
      pancreatic lipase (HPL). Total pancreatic lipase activity measurements using the
      pH-stat technique and tributyrin as substrate were combined with an HPL-specific
      ELISA. Based on the known specific activity of the purified HPL, its activity was
      deduced from the ELISA measurements, and the PPL activity was obtained by
      subtracting the HPL activity from the total pancreatic lipase activity. This
      assay was established and validated using various samples containing pure PPL and
      recombinant HPL or PE, mixed or not with human duodenal juice. Samples collected
      in vivo from patients treated with PE were also tested. It was found that PPL did
      not affect the HPL ELISA, and the indirect PPL assay gave a measurement accuracy
      of 6.6% with the samples containing pure PPL and 10% with those containing PE.
      This assay was also used successfully to discriminate between PPL and the
      endogenous HPL present in the duodenal contents of patients with severe
      pancreatic insufficiency treated with PE. This method might provide a useful
      means of assessing the availability of PEs at their site of action, in the
      absence of a PPL-specific ELISA.

PMID- 18814837
TI  - Characterization of PI3K class IA isoforms with regulatory subunit p55alpha using
      a scintillation proximity assay.
AB  - Differential activation of the phosphoinositide 3-kinase (PI3K)/AKT pathway has
      been linked to cancer. Activation occurs through gene amplification and
      activating mutations. High-frequency mutations in the gene encoding the p110alpha
      catalytic subunit of PI3K (PIK3CA) have been observed in a variety of tumors
      including colon, brain, breast, ovarian, and gastric. Inhibition of PI3K kinase
      activity may provide a specific way to treat multiple types of human cancer. A
      scintillation proximity assay (SPA) was developed to detect phosphatidylinositol
      3-kinase catalytic activity. Using this assay format, steady-state kinetic
      parameters were compared for the PI3K class IA enzymes p110alpha, p110beta, and
      p110delta, each coexpressed with the regulatory subunit p85alpha or splice
      variant p55alpha. Inhibition by the natural product wortmannin and LY294002 was
      detected with potencies consistent with alternate assay formats. Other
      biochemical assay formats have been described for phosphoinositide 3-kinases but
      each has its unique limitations. The simple, inexpensive, sensitive high
      throughput nature of the SPA format has advanced our knowledge of isoform
      specific enzymology and will facilitate the discovery of novel PI3K inhibitors.

PMID- 18814838
TI  - From 10,000 to 1: Selective synthesis and enzymatic evaluation of fluorescence
      resonance energy transfer peptides as specific substrates for chymopapain.
AB  - The synthesis and detailed enzymatic analysis of fluorescence resonance energy
      transfer (FRET)-based peptides as substrates for chymopapain are reported. The
      design of these substrates arose from a massively parallel high-throughput
      microarray screening process using peptide nucleic acid (PNA) encoding
      technology, allowing the identification of detailed substrate specificities of
      any protease. Two peptides so identified with chymopapain were observed to be
      excellent substrates with low micromolar K(m) values and turnover numbers on the
      order of hundreds per second. Mass spectroscopy studies showed unequivocally the
      specificity of chymopapain toward Ala, Pro, Val, and Lys for positions P(4) to
      P(1) while not presenting high specificity for residues in position P(1)'.

PMID- 18814839
TI  - Single-cell research: what determines its feasibility?
AB  - A general problem in single-cell research (SCR) is whether a representative cell
      is picked for analysis. In many cases, it may determine feasibility of SCR. Here,
      using a probability approach, we analyze this problem for laser tweezers Raman
      spectroscopy (LTRS), a promising technique for SCR. The results suggest that two
      main parameters determine the success and feasibility of SCR: the probability of
      picking a representative cell and the number of representative cells to be picked
      and analyzed. Both parameters determine the number of experiments required to
      obtain meaningful results. The approach is verified on several particular
      examples of SCR.

PMID- 18814840
TI  - Gene trapping identifies a putative tumor suppressor and a new inducer of cell
      migration.
AB  - Tumor necrosis factor alpha (TNFalpha) is a pleiotropic cytokine involved in
      apoptotic cell death, cellular proliferation, differentiation, inflammation, and
      tumorigenesis. In tumors it is secreted by tumor associated macrophages and can
      have both pro- and anti-tumorigenic effects. To identify genes regulated by
      TNFalpha, we performed a gene trap screen in the mammary carcinoma cell line MCF
      7 and recovered 64 unique, TNFalpha-induced gene trap integration sites. Among
      these were the genes coding for the zinc finger protein ZC3H10 and for the
      transcription factor grainyhead-like 3 (GRHL3). In line with the dual effects of
      TNFalpha on tumorigenesis, we found that ZC3H10 inhibits anchorage independent
      growth in soft agar suggesting a tumor suppressor function, whereas GRHL3
      strongly stimulated the migration of endothelial cells which is consistent with
      an angiogenic, pro-tumorigenic function.

PMID- 18814841
TI  - Generation of a 'humanized' hCYP1A1_1A2_Cyp1a1/1a2(-/-)_Ahrd mouse line harboring
      the poor-affinity aryl hydrocarbon receptor.
AB  - Herein, we describe generation of the hCYP1A1_1A2_Cyp1a1/1a2(-/-)_Ahr(d) mouse
      line, which carries human functional CYP1A1 and CYP1A2 genes in the absence of
      mouse Cyp1a1 and Cyp1a2 genes, in a (>99.8%) background of the C57BL/6J genome
      and harboring the poor-affinity aryl hydrocarbon receptor (AHR) from the DBA/2J
      mouse. We have characterized this line by comparing it to our previously created
      hCYP1A1_1A2_Cyp1a1/1a2(-/-)_Ahr(b1) line-which carries the same but has the high
      affinity AHR of the C57BL/6J mouse. By quantifying CYP1A1 and CYP1A2 mRNA in
      liver, lung and kidney of dioxin-treated mice, we show that dose-response curves
      in hCYP1A1_1A2_Cyp1a1/1a2(-/-)_Ahr(d) mice are shifted to the right of those in
      hCYP1A1_1A2_Cyp1a1/1a2(-/-)_Ahr(b1) mice-similar to, but not as robust as, dose
      response curves in DBA/2J versus C57BL/6J mice. This new mouse line is perhaps
      more relevant than the former to human risk assessment vis-a-vis human CYP1A1 and
      CYP1A2 substrates, because poor-affinity rather than high-affinity AHR occurs in
      the vast majority of the human population.

PMID- 18814842
TI  - Secretory and GM1 receptor binding role of N-terminal region of LTB in Vibrio
      cholerae.
AB  - Heat labile enterotoxin from enterotoxigenic Escherichia coli is similar to
      cholera toxin (CT) and is a leading cause of diarrhea in developing countries. It
      consists of an enzymatically active A subunit (LTA) and a carrier pentameric B
      subunit (LTB). In the current study, we evaluated the importance of the N
      terminal region of LTB by mutation analysis. Deletion of the glutamine (DeltaQ3)
      residue and a substitution mutation E7G in the alpha1 helix region led to defects
      in LTB protein secretion. Deletion of the proline residue (DeltaP2) caused a
      decrease in alpha helicity. The DeltaP2 mutant affected GM(1) ganglioside
      receptor binding activity without affecting LTB pentamer formation. Upon
      refolding/reassembly, the DeltaP2 mutant showed defective biological activity.
      The single substitution mutation (E7D) strengthened the helix, imparting
      structural stability and thereby improved the GM(1) ganglioside receptor binding
      activity. Our results demonstrate the important role of N-terminal alpha1 helix
      in maintaining the structural stability and the integrity of GM(1) ganglioside
      receptor binding activity.

PMID- 18814843
TI  - New case of long-term persistence of Paranosema locustae (Microsporidia) in
      melanopline grasshoppers (Orthoptera: Acrididae: Melanoplinae) of Argentina.
AB  - We report an additional case of long-term persistence of Paranosema locustae in
      grasshoppers of Argentina. The pathogen was introduced from North America on
      rangeland at Loncopue, Neuquen province. Microsporidia were not detected in pre
      introduction samples whereas infected grasshoppers were found 11 years after
      introduction. Affected grasshoppers were the melanoplines Dichroplus elongatus,
      Dichroplus maculipennis, and Scotussa lemniscata, some of them with high spore
      loads. The case highlights the ability of P. locustae to recycle in local
      grasshopper communities by parasitizing susceptible species other than the
      natural hosts.

PMID- 18814844
TI  - Strain differences in toxic effects of long-lasting isoflurane anaesthesia
      between Wistar rats and Sprague Dawley rats.
AB  - We investigated if long-lasting (5 h) anaesthesia with isoflurane has different
      pharmacological effects in two different rat strains: Wistar and Sprague Dawley.
      The mean blood pressure was 34% higher in Sprague Dawley rats as compared to the
      Wistar rats (p = 0.04). In Wistar rats, the pH value decreased to 7.1, lactate
      increased by 53%, creatinine increased 2.7-fold, alanine amino transferase and
      aspartate amino transferase increased more than 4-fold and lactate dehydrogenase
      increased 9-fold (p < 0.05). There were no changes in laboratory parameters in
      Sprague Dawley rats. This indicates that the Wistar rats were more sensitive to a
      5 h anaesthesia with isoflurane after a premedication with ketamin/xylazine in
      the described study design.

PMID- 18814845
TI  - Regeneration in axolotls: a model to aim for!
AB  - Urodele amphibians such as the axolotl are the champions of tissue regeneration
      amongst vertebrates. These animals have mastered the ability to repair and
      replace most of their tissues following damage or amputation even well into
      adulthood. In fact it seems that the ability of these organisms to regenerate
      perfectly is not affected by their age. In addition to being able to regenerate,
      these animals display a remarkable resistance to cancer. They therefore represent
      a unique model organism to study regeneration and cancer resistance in
      vertebrates. The need for this research is even more pressing at the dawn of the
      21st century as we are faced with an ever aging world population which has to
      deal with an increase in organ failure and cancer incidence. Hopefully, this mini
      review will put in perspective some of the reasons why studying tissue
      regeneration in salamanders could yield significant knowledge to help
      regenerative medicine achieve the desired goal of allowing humans to repair and
      regenerate some of their own tissues as they age.

PMID- 18814846
TI  - Peripheral lipopolysaccharide (LPS) challenge promotes microglial hyperactivity
      in aged mice that is associated with exaggerated induction of both pro
      inflammatory IL-1beta and anti-inflammatory IL-10 cytokines.
AB  - In the elderly, systemic infection is associated with an increased frequency of
      behavioral and cognitive complications. We have reported that peripheral
      stimulation of the innate immune system with lipopolysaccharide (LPS) causes an
      exaggerated neuroinflammatory response and prolonged sickness/depressive-like
      behaviors in aged BALB/c mice. Therefore, the purpose of this study was to
      determine the degree to which LPS-induced neuroinflammation was associated with
      microglia-specific induction of neuroinflammatory mediators. Here, we show that
      peripheral LPS challenge caused a hyperactive microglial response in the aged
      brain associated with higher induction of inflammatory IL-1beta and anti
      inflammatory IL-10. LPS injection caused a marked induction of mRNA expression of
      both IL-1beta and IL-10 in the cortex of aged mice compared to adults. In the
      next set of studies, microglia (CD11b(+)/CD45(low)) were isolated from the brain
      of adult and aged mice following experimental treatments. An age-dependent
      increase in major histocompatibility complex (MHC) class II mRNA and protein
      expression was detected in microglia. Moreover, peripheral LPS injection caused a
      more pronounced increase in IL-1beta, IL-10, Toll-like receptor (TLR)-2, and
      indoleamine 2,3-dioxygenase (IDO) mRNA levels in microglia isolated from aged
      mice than adults. Intracellular cytokine protein detection confirmed that
      peripheral LPS caused the highest increase in IL-1beta and IL-10 levels in
      microglia of aged mice. Finally, the most prominent induction of IL-1beta was
      detected in MHC II(+) microglia from aged mice. Taken together, these findings
      provide novel evidence that age-associated priming of microglia plays a central
      role in exaggerated neuroinflammation induced by activation of the peripheral
      innate immune system.

PMID- 18814847
TI  - Endothelin-1 promotes migration of endothelial cells through the activation of
      ARF6 and the regulation of FAK activity.
AB  - Several proteins act in concert to promote remodeling of the actin cytoskeleton
      during migration. This process is highly regulated by small GTP-binding proteins
      of the ADP-ribosylation factor (ARF) family of proteins. Here, we show that
      endothelin-1 (ET-1) can promote the activation of ARF6 and migration of
      endothelial cells through the activation of ET(B) receptors. Inhibition of ARF6
      expression using RNA interference markedly impairs basal and ET-1 stimulated cell
      migration. In contrast, depletion of ARF1 has no significant effect. In order to
      delineate the underlying mechanism, we examined the signaling events activated in
      endothelial cells following ET-1 stimulation. Here, we show that this hormone
      promotes the phosphorylation of focal adhesion kinase (FAK), Erk1/2, and the
      association of FAK to Src, as well as of FAK to GIT1. These have been shown to be
      important for the formation and turnover of focal adhesions. In non-stimulated
      cells, depletion of ARF6 leads to increased FAK and Erk1/2 phosphorylation,
      similar to what is observed in ET-1 treated cells. In these conditions, FAK is
      found constitutively associated with the soluble tyrosine kinase, Src. In
      contrast, depletion of ARF6 impairs the ability of GIT1 to form an agonist
      promoted complex with FAK, thereby preventing disassembly of focal adhesions. As
      a consequence, ARF6 depleted endothelial cells are impaired in their ability to
      form capillary tubes. Taken together, our data suggest that ARF6 is central in
      regulating focal adhesion turnover in endothelial cells. Our study provides a
      molecular mechanism by which, this small GTPase regulates cell motility, and
      ultimately angiogenesis.

PMID- 18814848
TI  - pTONA5: a hyperexpression vector in Streptomycetes.
AB  - We constructed the Streptomyces hyperexpression vector pTONA5 based on pIJ702
      vector; it includes a metalloendopeptidase (SSMP) promoter isolated from
      Streptomyces cinnamoneus TH-2 and a metalloendopeptidase terminator isolated from
      Streptomyces aureofaciens TH-3. The vector contains recognition sites for
      restriction enzymes NdeI and EcoRI/XbaI/HindIII between the promoter and
      terminator to facilitate heterologous gene cloning. The plasmids were transferred
      from Escherichia coli to streptomycetes via conjugation from oriT; the
      transformants were able to be selected using kanamycin and/or thiostrepton. The
      SSMP promoter functions constitutively in the presence of a rich inorganic
      phosphate source and glucose. We constructed expression plasmids including three
      Streptomyces aminopeptidases-leucine aminopeptidase, proline aminopeptidase
      (PAP), and aminopeptidase P (APP)-using the pTONA5 vector and Streptomyces
      lividans. Although they lack signal peptides for secretion, PAP and APP were
      secreted at high levels in the culture broth.

PMID- 18814849
TI  - A human cell-derived in vitro coupled transcription/translation system optimized
      for production of recombinant proteins.
AB  - The aim of this study was to develop an efficient cell-free protein expression
      system derived from mammalian cells. We established a HeLa cell-based in vitro
      coupled transcription/translation system with T7 RNA polymerase and a plasmid
      that harbored a T7 promoter/terminator unit. To enhance protein synthesis in the
      coupled system, we placed the encephalomyocarditis virus (EMCV) internal ribosome
      entry site (IRES) or the hepatitis C virus (HCV) IRES between the T7 promoter and
      the coding region of the plasmid. Remarkably, we found that these IRES-dependent
      systems were able to produce large proteins including GCN2 (160 kD), Dicer (200
      kD) and mTOR (260 kD) to levels detectable on SDS-PAGE by Comassie Brilliant Blue
      staining. We purified the synthesized proteins to near homogeneity, and validated
      their functionalities in the appropriate biochemical assays. In conclusion, the
      HeLa cell-based in vitro coupled transcription/translation system using the EMCV
      or HCV IRES is a convenient tool, particularly for the production of large
      recombinant proteins.

PMID- 18814850
TI  - Expression of Pisum sativum SAD polypeptides in production hosts and in planta:
      tetrameric organization of the protein.
AB  - In Pisum sativum, the short-chain alcohol dehydrogenase-like protein (SAD) gene
      family consists of at least three members (SAD-A, -B, and -C). Expression of two
      of these genes (SAD-A and -C) in Escherichia coli or Pichia pastoris resulted in
      full-length soluble proteins. Purified SAD-A was used as antigen for antibody
      production in rabbits. With these antibodies the recombinant SAD-C protein (which
      was most highly expressed of the two isoforms) was shown to be a tetramer
      consisting of a dimer of dimers. The SAD genes are transiently expressed in
      plants by short exposures to ultraviolet-B radiation (UV-B), as judged by
      northern blotting. In turn, mRNA accumulation leads to formation of SAD protein
      in leaf and stem tissue upon prolonged UV-B irradiation.

PMID- 18814851
TI  - Three-dimensional structure of human chromatin accessibility complex hCHRAC by
      electron microscopy.
AB  - ATP-dependent chromatin remodeling complexes modulate the dynamic assembly and
      remodeling of chromatin involved in DNA transcription, replication, and repair.
      There is little structural detail known about these important multiple-subunit
      enzymes that catalyze chromatin remodeling processes. Here we report a three
      dimensional structure of the human chromatin accessibility complex, hCHRAC, using
      single particle reconstruction by negative stain electron microscopy. This
      structure shows an asymmetric 15x10x12nm disk shape with several lobes protruding
      out of its surfaces. Based on the factors of larger contact area, smaller steric
      hindrance, and direct involvement of hCHRAC in interactions with the nucleosome,
      we propose that four lobes on one side form a multiple-site contact surface 10nm
      in diameter for nucleosome binding. This work provides the first determination of
      the three-dimensional structure of the ISWI-family of chromatin remodeling
      complexes.

PMID- 18814852
TI  - Mitochondrial and nuclear phylogeny of circum-Mediterranean tree frogs from the
      Hyla arborea group.

PMID- 18814853
TI  - Inhibition by lithium of the nitrergic relaxation of rat anococcygeus muscle.
AB  - In the present study, we evaluated the effect of lithium on the nitric oxide (NO)
      mediated nonadrenergic noncholinergic (NANC) relaxation of rat anococcygeus
      muscle. The isolated precontracted (phenylephrine, 7.5 microM) rat anococcygeus
      muscle were relaxed via electrical field stimulation (5 Hz) in the absence or
      presence of lithium (0.5, 1, and 5mM) or in tissues excised from ex vivo lithium
      (600 mg/L in drinking water for 30 days)-treated animals. Effects of the NO
      synthase (NOS) inhibitor L-NAME (0.03 and 100 microM) or guanylyl cyclase
      inhibitor ODQ (1 microM) and NO precursor L-arginine (1mM) on relaxations were
      investigated. Effect of either in vitro (1 and 5mM) or ex vivo lithium treatment
      on relaxation to the NO donor sodium nitroprusside (SNP; 0.1-1000 microM) was
      also investigated on phenylephrine-contracted strips. The NANC relaxation was
      significantly reduced by in vitro (1 and 5mM; up to P<0.01) and ex vivo lithium
      treatment (P<0.001). L-NAME (100 microM and 1mM) and ODQ (1 and 10 microM)
      significantly inhibited NANC relaxations in either control or lithium-treated
      strips. Combination of lithium (0.5mM) with L-NAME (0.03 microM) significantly
      (P<0.001) reduced the NANC relaxation. Although 1mM l-arginine had no effect on
      relaxations, it prevented their inhibition by both in vitro (1 and 5mM) and ex
      vivo lithium of relaxations. SNP produced concentration-dependent relaxation in
      precontracted rat anococcygeus muscle which was not altered by lithium treatment.
      Reverse transcription polymerase chain reaction (RT-PCR) revealed a significant
      increase in the neuronal NOS expression in the anococcygeus muscle of ex vivo
      lithium-treated animals compared with controls. Our experiments suggested that
      both ex vivo and in vitro lithium administration attenuated the NO-mediated
      neurogenic relaxation of isolated rat anococcygeus muscle.

PMID- 18814854
TI  - Validation of the Spanish version of the Side Effect and Life Satisfaction
      Inventory in patients with epilepsy.
AB  - OBJECTIVE: The goal of the study described here was to obtain psychometric
      validation of the Spanish version of the 38-item Side Effects and Life
      Satisfaction (SEALS) Inventory. METHODS: A cross-cultural adaptation of the
      inventory was performed. A total of 595 patients with epilepsy were included in a
      multicenter cross-sectional study. The SEALS Inventory was completed, together
      with the Hospital Anxiety and Depression Scale and SF-12 Health Survey. RESULTS:
      The mean SEALS score was 60.7. SEALS presented high internal consistency, with a
      Cronbach alpha coefficient of 0.93, and good test-retest reliability, with an
      intraclass correlation coefficient of 0.92. The pattern of correlations with the
      Hospital Anxiety and Depression Scale and SF-12 Health Survey indicated good
      convergent and divergent validity. SEALS scores discriminated patients according
      to epilepsy-related factors, emotional disturbances, and the generic quality of
      life. CONCLUSION: The Spanish version of the SEALS Inventory is a valid
      psychometric instrument. It may be used in routine clinical practice and in
      clinical trials in patients with epilepsy to capture the cognitive and behavioral
      aspects of quality of life.

PMID- 18814855
TI  - Dynamic transition of Dnmt3b expression in mouse pre- and early post-implantation
      embryos.
AB  - The de novo DNA methyltransferases, Dnmt3a and Dnmt3b, are responsible for the
      creation of DNA methylation patterns in mouse development. Dnmt3b is more highly
      expressed in early developmental stages than Dnmt3a, and is thought to have an
      important role in the epigenetic gene regulation during early embryogenesis.
      Previous reports suggest that Dnmt3b is expressed preferentially in the embryonic
      lineage, but less in the extra-embryonic lineage, in early post-implantation
      embryos. However, it is unclear when this lineage-specific differential
      expression is established. Here we demonstrate that Dnmt3b shows a dynamic
      expression change during pre- and early post-implantation development. Contrary
      to the expectation, Dnmt3b is preferentially expressed in the trophectoderm
      rather than the inner cell mass at the mid blastocyst stage. Subsequently, the
      spatial Dnmt3b expression gradually changes during pre- and early post
      implantation development, and finally Dnmt3b expression is settled in the
      embryonic lineage at the epiblast stage. The findings are consistent with the
      role for Dnmt3b in cell-lineage specification and the creation of lineage
      specific DNA methylation patterns.

PMID- 18814856
TI  - Electrostatic heteroaggregation regimes in colloidal suspensions.
AB  - Despite of their importance for many industrial applications and the
      understanding of natural phenomena, heteroaggregation processes have not been in
      the focus of attention of the scientific community until quite recently. Still
      nowadays, their tremendously complex nature turns a detailed experimental and
      theoretical treatment of these processes into a difficult task. Hence, we have
      limited the scope of this review to electrostatic heteroaggregation arising in
      symmetric two-component systems, i.e., those with the same concentration of
      cationic and anionic particles. The short and long-time aggregation kinetics will
      be addressed not only from an experimental but also from a theoretical and
      simulation point of view at almost six orders of magnitude of electrolyte
      concentration. The different aggregation regimes will be identified and described
      in detail.

PMID- 18814857
TI  - Cataract halos: a driving hazard in aging populations. Implication of the
      Halometer DG test for assessment of intraocular light scatter.
AB  - OBJECTIVE AND BACKGROUND: Cataract, regardless of etiology, results in light
      scatter and subjective glare. Senile cataract is emerging as a crucial factor in
      driving safely, particularly in night driving and adverse weather conditions. The
      authors examined this visual impairment using a new Halometer DG test in the eyes
      of older adult drivers with and without cataract. METHOD: Examined subjects
      consisted of n=65 older adults with cataract in one or both eyes and n=72 adult
      drivers who did not have a cataract in either eye. Subjects were examined for
      distance high contrast visual acuity (VA) and red/green disability glare (DG)
      with a new halo generating instrument. Subjects also completed a subjective
      Driving Habits Questionnaire (DHQ), designed to obtain information about driving
      during the past year. RESULTS: DG increased with age of the driver. VA and
      Halometer DG testing of better and worse eyes prognosticated impairments which
      significantly affect driving performance. Cataract subjects demonstrated
      increased Halometer DG scores and were two to four times more likely to report
      difficulty with driving at night and with challenging driving situations than
      were cataract-free drivers. CONCLUSION: DG is a specific cataract-induced
      functional age-related risk factor of driving difficulty, easily measured by a
      technician with a new Halometer DG device. APPLICATION: Optometrists and
      ophthalmologists should incorporate Halometer DG testing in their pre-examination
      vision testing rooms for patients over age 55, and also perform this test on
      others who complain about glare. Traffic safety engineers should incorporate
      automotive optical-microprocessor-aided tests for DG into cars, to alert drivers
      of mild functional impairments and progressive degrees of DG sensitization.

PMID- 18814858
TI  - Permanent reduction of mandibular size and bone stiffness induced in post-weaning
      rats by cyclophosphamide.
AB  - It has been previously reported that several doses of cyclophosphamide (CPA)
      reduce body weight gain, diaphyseal torsional strength and longitudinal femoral
      growth in the growing rat. The present study was thus designed to estimate both
      the initial and the possible long-term effects of CPA treatment, by analyzing
      mandibular dimensions and biomechanical performance of the bone in adulthood in
      rats treated with the drug around weaning. Female Sprague-Dawley rats (N=20), 26
      d of age, received 100mg/kg of CPA by the intraperitoneal route during days 0, 7
      and 21 of the experimental period. Controls (C) received saline. Groups of rats
      were sacrificed at day 28 to estimate initial changes induced by the drug and on
      day 126 in order to determine long-term effects. The dimensions of the excised
      mandibles were measured directly between anatomical points; the geometry and
      material biomechanical quality of mandibular bone were assessed using a three
      point bending mechanical test in an Instron Universal Testing Machine model 4442.
      CPA reduced body weight, body length and mandibular size (posterior part of the
      bone) significantly, when the parameters were measured at day 28. They did not
      recover with time, which means that catch-up growth did not occur and that the
      overall growth of the body was permanently affected by the drug. CPA treatment
      was also associated with a marked depression of the natural increase in the
      mandibular bone mass (cross-sectional area). The bending cross-sectional moment
      of inertia of the fracture sections (xCSMI) was also negatively affected by
      treatment. Significant decreases of both ultimate load and stiffness were also
      observed. The above structural parameters did not recover enough with time to
      attain control values at the end of the study. The intrinsic stiffness (E) of the
      mandibular bone was not affected by treatment. These findings suggest that CPA
      treatment during early postnatal life causes permanent changes in mandibular
      morphology and affects the adaptation of mandibular bone architecture to body
      growth, thus not allowing complete compensation at the end of the study because
      of an inadequate distribution of the resistive material through its cross-section
      rather than a qualitative impairment of cortical bone.

PMID- 18814859
TI  - Increased brain histamine H1 receptor binding in patients with anorexia nervosa.
AB  - BACKGROUND: The central histaminergic neuron system modulates various brain
      functions, including eating behavior. We hypothesized that women have higher
      density of histamine H1 receptor (H1R) in the limbic system than men and that the
      density of central H1R is increased in patients with anorexia nervosa (AN).
      METHODS: Subjects were 12 female AN patients, 12 healthy female subjects, and 11
      healthy male subjects. Positron emission tomography with H1R radioligand
      [(11)C]doxepin was performed on all subjects and regions of interest based
      analysis was conducted to evaluate brain H1R binding potential (BP). Abnormal
      eating behavior, depression, and anxiety of subjects were evaluated using the
      Eating Attitude Test-26 (EAT-26), Self-Rating Depression Scale (SDS), and State
      Trait Anxiety Inventory (STAI), respectively. RESULTS: Binding potential of
      [(11)C]doxepin in female subjects was significantly higher than that in male
      subjects at the following brain sites: amygdala, hippocampus, medial prefrontal
      cortex, orbitofrontal cortex, and temporal cortex. Anorexia nervosa patients
      showed significantly higher BP of [(11)C]doxepin in the amygdala and lentiform
      nucleus than the control female subjects. In AN patients, BP of [(11)C]doxepin in
      the amygdala and thalamus negatively correlated with EAT-26 scores. There was a
      significant negative correlation between BP of [(11)C]doxepin and SDS or STAI
      scores in the amygdala, anterior cingulate cortex, and orbitofrontal cortex of AN
      patients. CONCLUSIONS: These findings support the hypothesis that women have
      higher H1R density in the limbic system than men and suggest that AN patients may
      have higher expression of H1R in the limbic brain, particularly in the amygdala.

PMID- 18814860
TI  - Early and late components of error monitoring in violent offenders with
      psychopathy.
AB  - BACKGROUND: One of the most recognizable features of psychopathy is the reduced
      ability to successfully learn and adapt overt behavior. This might be due to
      deficient processing of error information indicating the need to adapt controlled
      behavior. METHODS: Event-related potentials (ERPs) and behavioral components of
      error-monitoring processes were investigated in 16 individuals with psychopathy
      and in 18 healthy subjects. A letter version of the Eriksen flanker task was used
      in two conditions. The first condition (normal condition) required participants
      to press one of two buttons depending on the identity of the target stimulus. The
      second condition (signaling condition) required them to signal each time they had
      committed an error by making a second press on a signaling button. Early stages
      of error monitoring were investigated by using the error-related negativity
      (ERN/Ne) and post-error slowing as indexes. Later stages were explored by
      examining the error positivity (Pe) and signaling rates. RESULTS: Both groups
      showed similar ERN amplitudes and amounts of post-error slowing. The psychopathic
      group exhibited both reduced Pe amplitudes and diminished error-signaling rates
      compared with the control group. CONCLUSIONS: Individuals with psychopathy show
      intact early error processing and automatic behavioral adaptation but have
      deficits in later stages of error processing and controlled behavioral
      adaptation. This is an indication that individuals with psychopathy are unable to
      effectively use error information to change their behavior adequately.

PMID- 18814861
TI  - White matter tractography in bipolar disorder and schizophrenia.
AB  - BACKGROUND: Abnormalities of white matter integrity have been repeatedly
      demonstrated in both schizophrenia and bipolar disorder with voxel based methods.
      Because these methods are limited in their ability to localize deficits to
      specific tracts, we sought to investigate alterations in fractional anisotropy
      (FA) in the uncinate fasciculus and anterior thalamic radiation with
      probabilistic tractography. METHODS: Individuals with schizophrenia (n = 25) or
      bipolar disorder (n = 40) were recruited from families with two or more affected
      members and age-matched to a control group (n = 49). All participants underwent
      diffusion tensor magnetic resonance imaging that was subsequently analyzed with
      probabilistic tractography. Mean FA was calculated bilaterally for the uncinate
      and anterior thalamic radiation and compared between groups with repeated
      measures analysis of variance. RESULTS: Patients with schizophrenia or bipolar
      disorder showed common reductions in the uncinate fasciculus and anterior
      thalamic radiation. These reductions were unrelated to age, duration of illness,
      current medication, or current psychiatric symptoms in all patients or the
      lifetime presence of psychotic symptoms in bipolar subjects. CONCLUSIONS:
      Patients with schizophrenia or bipolar disorder show common abnormalities in the
      uncinate fasciculus and anterior thalamic radiation that fail to respect
      traditional diagnostic boundaries. These deficits might be related to shared risk
      factors and disease mechanisms common to both disorders.

PMID- 18814862
TI  - Improved odor sensitivity in attention-deficit/hyperactivity disorder.
AB  - BACKGROUND: Deficits in olfactory function are common features in
      neurodegenerative and neuropsychiatric disorders. In Parkinson's disease,
      olfactory deficits were found in up to 90% of patients, and there is evidence for
      dopaminergic dysfunction underlying these deficits. Because of the involvement of
      the dopamine system in the pathophysiology of attention-deficit/hyperactivity
      disorder (ADHD), olfactory function was investigated in children with the
      disorder. METHODS: We assessed odor threshold, identification, and discrimination
      in 20 children and adolescents with ADHD without medication, 20 patients with
      ADHD treated with methylphenidate, and 20 healthy control subjects matched for
      IQ, age, and sex. RESULTS: Odor sensitivity was higher (lower threshold) in ADHD
      patients without medication than in healthy control subjects (p < .004; Cohen's d
      = 1.273), whereas medicated patients did not differ significantly from healthy
      control subjects. No significant differences between groups with regard to odor
      discrimination or identification were detected. CONCLUSIONS: Selectively improved
      odor sensitivity in children with ADHD is reported for the first time, whereas
      odor discrimination and identification were unaffected. Stimulant medication
      normalized the odor sensitivity threshold. It is proposed that dopaminergic
      dysregulation is involved in this phenomenon.

PMID- 18814863
TI  - Absence of embodied empathy during pain observation in Asperger syndrome.
AB  - BACKGROUND: Asperger syndrome (AS) is a neurodevelopmental condition within the
      autism spectrum conditions (ASC) characterized by specific difficulties in
      communication, social interaction, and empathy that is essential for sharing and
      understanding others' feelings and emotions. Although reduced empathy is
      considered a core feature of ASC, neurophysiological evidence of empathic
      deficits before and below mentalizing and perspective taking is lacking. We
      explored whether people with AS differ from neurotypical control participants in
      their empathic corticospinal response to the observation of others' pain and the
      modulatory role played by phenomenal experience of observed pain and personality
      traits. METHODS: Sixteen right-handed men with AS (aged 28.0+/-7.2 years) and 20
      neurotypical controls (aged 25.3+/-6.7 years) age, sex, and IQ matched, underwent
      single-pulse transcranial magnetic stimulation during observation of painful and
      nonpainful stimuli affecting another individual. RESULTS: When observing other's
      pain, participants with AS, in contrast to neurotypical control participants, did
      not show any amplitude reduction of motor-evoked potentials recorded from the
      muscle vicariously affected by pain, nor did their neurophysiological response
      correlate with imagined pain sensory qualities. Participants with AS represented
      others' pain in relation to the self-oriented arousal experienced while watching
      pain videos. CONCLUSIONS: Finding no embodiment of others' pain provides
      neurophysiological evidence for reduced empathic resonance in people with AS and
      indicates that their empathic difficulties involve not only cognitive dimensions
      but also sensorimotor resonance with others. We suggest that absence of embodied
      empathy may be linked to changes at very basic levels of neural processing.

PMID- 18814864
TI  - Epigenetic regulation in human brain-focus on histone lysine methylation.
AB  - Alterations in RNA levels are frequently reported in brain of subjects diagnosed
      with autism, schizophrenia, depression, and other psychiatric diseases, but it
      remains unclear whether the underlying molecular pathology involves changes in
      gene expression, as opposed to alterations in messenger RNA processing. Pre
      clinical studies have revealed that stress, drugs, and a variety of other
      environmental factors lead to changes in RNA levels in brain via epigenetic
      mechanisms, including modification of histone proteins. A number of site-specific
      modifications of the nucleosome core histones-including the trimethylated forms
      of histone H3 lysines K4, K9, and K27-are of particular interest for postmortem
      research, because these marks differentiate between active and inactive chromatin
      and seem to remain relatively stable during tissue autolysis. Therefore, histone
      methylation profiling at promoter regions could provide important clues about
      mechanisms of gene expression in human brain during development and in disease.
      Intriguingly, mutations within the genes encoding the H3K9-specific
      methyltransferase, EHMT1, and the H3K4-specific histone demethylase,
      JARID1C/SMCX, have been linked to mental retardation and autism, respectively. In
      addition, the H3K4-specific methyltransferase, MLL1, is essential for hippocampal
      synaptic plasticity and might be involved in cortical dysfunction of some cases
      of schizophrenia. Together, these findings emphasize the potential significance
      of histone lysine methylation for orderly brain development and also as a
      molecular toolbox to study chromatin function in postmortem tissue.

PMID- 18814865
TI  - Progressive deformation of deep brain nuclei and hippocampal-amygdala formation
      in schizophrenia.
AB  - BACKGROUND: Progressive decreases in cortical gray matter volume have been
      reported in schizophrenia. However, studies of progressive change in deep brain
      nuclei and hippocampal-amygdala formation have not yielded consistent findings.
      METHODS: Two high-resolution, T1-weighted magnetic resonance images were
      collected 2 years apart in 56 schizophrenia and 62 control subjects. Large
      deformation high-dimensional brain mapping was used to generate surfaces for deep
      brain nuclei and hippocampal-amygdala formation at baseline and follow-up.
      Repeated-measures analysis of variance was used to test for longitudinal changes
      in volume and shape. RESULTS: The pattern of progressive changes in the deep
      brain nuclei and hippocampal-amygdala formation in schizophrenia and control
      subjects was variable. Of the structures that receive direct projections from the
      cortex, the thalamus, caudate nucleus, nucleus accumbens, and hippocampus showed
      changes specific to subjects with schizophrenia, and changes in the amygdala and
      putamen were similar in both groups. Although different at baseline, no
      progressive change was observed in the globus pallidus, which does not receive
      direct projections from the cortex. CONCLUSIONS: These findings suggest that the
      disease process of schizophrenia is associated with progressive effects on brain
      structure and that brain structures that receive direct, excitatory connections
      from the cortex may be more likely to show progressive changes, compared with
      brain structures that receive indirect, inhibitory connections from the cortex.
      These findings are also somewhat consistent with the hypothesis that overactivity
      of excitatory pathways in the brain may contribute to the neural degeneration
      that occurs in at least a subgroup of individuals with schizophrenia.

PMID- 18814866
TI  - Fatty acid amide hydrolase inhibition heightens anandamide signaling without
      producing reinforcing effects in primates.
AB  - BACKGROUND: CB(1) cannabinoid receptors in the brain are known to participate in
      the regulation of reward-based behaviors. However, the contribution of each of
      the endocannabinoid transmitters, anandamide and 2-arachidonoylglycerol (2-AG),
      to these behaviors remains undefined. To address this question, we assessed the
      effects of URB597, a selective anandamide deactivation inhibitor, as a reinforcer
      of drug-seeking and drug-taking behavior in squirrel monkeys. METHODS: We
      investigated the reinforcing effects of the fatty acid amide hydrolase (FAAH)
      inhibitor URB597 in monkeys trained to intravenously self-administer Delta(9)
      tetrahydrocannabinol (THC), anandamide, or cocaine and quantified brain
      endocannabinoid levels using liquid chromatography/mass spectrometry. We measured
      brain FAAH activity using an ex vivo enzyme assay. RESULTS: URB597 (.3 mg/kg,
      intravenous) blocked FAAH activity and increased anandamide levels throughout the
      monkey brain. This effect was accompanied by a marked compensatory decrease in 2
      AG levels. Monkeys did not self-administer URB597, and the drug did not promote
      reinstatement of extinguished drug-seeking behavior previously maintained by THC,
      anandamide, or cocaine. Pretreatment with URB597 did not modify self
      administration of THC or cocaine, even though, as expected, it significantly
      potentiated anandamide self-administration. CONCLUSIONS: In the monkey brain, the
      FAAH inhibitor URB597 increases anandamide levels while causing a compensatory
      down-regulation in 2-AG levels. These effects are accompanied by a striking lack
      of reinforcing properties, which distinguishes URB597 from direct-acting
      cannabinoid agonists such as THC. Our results reveal an unexpected functional
      heterogeneity within the endocannabinoid signaling system and suggest that FAAH
      inhibitors might be used therapeutically without risk of abuse or triggering of
      relapse to drug abuse.

PMID- 18814868
TI  - X-ray crystallographic and high-resolution NMR spectroscopy characterization of
      4,6-di-O-acetyl-2,3-dideoxy-alpha-D-erythro-hex-2-enopyranosyl sulfamide.
AB  - Single crystal X-ray diffraction and high-resolution (1)H and (13)C NMR spectral
      data for 4,6-di-O-acetyl-2,3-dideoxy-alpha-D-erythro-hex-2-enopyranosyl
      sulfamide, a selective inhibitor of carbonic anhydrase isozyme IX, are reported.
      The (0)H(5) was found to be the preferred form for this glycosyl sulfamide, both
      in the crystal lattice and in solution.

PMID- 18814867
TI  - Cognitive control and white matter callosal microstructure in methamphetamine
      dependent subjects: a diffusion tensor imaging study.
AB  - BACKGROUND: Methamphetamine (MA) abuse causes damage to structures within the
      human cerebrum, with particular susceptibility to white matter (WM).
      Abnormalities have been reported in anterior regions with less evidence of
      changes in posterior regions. Methamphetamine abusers have also shown deficits on
      attention tests that measure response conflict and cognitive control. METHODS: We
      examined cognitive control with a computerized measure of the Stroop selective
      attention task and indices of WM microstructure obtained from diffusion tensor
      imaging (DTI) in the callosal genu and splenium of 37 currently abstinent MA
      abusers and 17 non-substance abusing control subjects. Measurements of fractional
      anisotropy (FA), apparent diffusion coefficient (ADC) of callosal fibers, and
      diffusion tensor eigenvalues were obtained in all subjects. RESULTS: The MA
      abusers exhibited greater Stroop reaction time interference (i.e., reduced
      cognitive control) (p = .04) compared with control subjects. After correcting for
      multiple comparisons, FA within the genu correlated significantly with measures
      of cognitive control in the MA abusers (p = .04, Bonferroni corrected) but not in
      control subjects (p = .26). Group differences in genu but not splenium FA were
      trend significant (p = .09). CONCLUSIONS: Methamphetamine abuse seems to alter
      anterior callosal WM microstructure with less evidence of change within posterior
      callosal WM microstructure. The DTI indices within the genu but not splenium
      correlated with measures of cognitive control in chronic MA abusers.

PMID- 18814869
TI  - Paranormal experience and the COMT dopaminergic gene: a preliminary attempt to
      associate phenotype with genotype using an underlying brain theory.
AB  - Paranormal belief and suggestibility seem related. Given our recent findings
      outlining a putative association between suggestibility and a specific
      dopaminergic genetic polymorphism, we hypothesized that similar exploratory
      genetic data may offer supplementary insights into a similar correlation with
      paranormal belief. With more affordable costs and better technology in the
      aftermath of the human genome project, genotyping is increasingly ubiquitous.
      Compelling brain theories guide specific research hypotheses as scientists begin
      to unravel tentative relationships between phenotype and genotype. In line with a
      dopaminergic brain theory, we tried to correlate a specific phenotype concerning
      paranormal belief with a dopaminergic gene (COMT) known for its involvement in
      prefrontal executive cognition and for a polymorphism that is positively
      correlated with suggestibility. Although our preliminary findings are
      inconclusive, the research approach we outline should pave the road to a more
      scientific account of elucidating paranormal belief.

PMID- 18814871
TI  - Effects of prenatal exposure to organochlorines on thyroid hormone status in
      newborns from two remote coastal regions in Quebec, Canada.
AB  - BACKGROUND: Several prospective studies have revealed that prenatal exposure to
      polychlorinated biphenyls (PCBs) and other organochlorine compounds (OCs) affect
      neurodevelopment during infancy. One of the mechanisms by which PCBs might
      interfere with neurodevelopment is a deficit in thyroid hormone (TH)
      concentrations. OBJECTIVES: We investigated the potential impact of
      transplacental exposure to PCBs and hexachlorobenzene (HCB) on TH concentrations
      in neonates from two remote coastal populations exposed to OCs through the
      consumption of seafood products. METHODS: Blood samples were collected at birth
      from the umbilical cord of neonates from Nunavik (n=410) and the Lower North
      Shore of the St. Lawrence River (n=260) (Quebec, Canada) for thyroid parameters
      [thyroid-stimulating hormone (TSH), free T4 (fT4), total T3 (tT3), and thyroxine
      binding globuline (TBG)] and contaminants analyses. RESULTS: In multivariate
      models, umbilical cord plasma concentrations of PCB 153, the predominant PCB
      congener, were not associated with TH and TSH levels in both populations.
      Prenatal exposure to HCB was positively associated with fT4 levels at birth in
      both populations (Nunavik, beta=0.12, p=0.04; St. Lawrence, beta=0.19, p<0.01),
      whereas TBG concentrations were negatively associated with PCB 153 concentrations
      (beta=-0.13, p=0.05) in the St. Lawrence cohort. CONCLUSION: OCs levels were not
      associated to a reduction in THs in neonates from our two populations. Essential
      nutrients derived from seafood such as iodine may have prevented the negative
      effects of OCs on the thyroid economy during fetal development.

PMID- 18814870
TI  - The transliminal brain at rest: baseline EEG, unusual experiences, and access to
      unconscious mental activity.
AB  - Transliminality reflects individual differences in the threshold at which
      unconscious processes or external stimuli enter into consciousness. Individuals
      high in transliminality possess characteristics such as magical ideation, belief
      in the paranormal, and creative personality traits, and also report the
      occurrence of manic/mystic experiences. The goal of the present research was to
      determine if resting brain activity differs for individuals high versus low in
      transliminality. We compared baseline EEG recordings (eyes-closed) between
      individuals high versus low in transliminality, assessed using The Revised
      Transliminality Scale of Lange et al. (2000). Identifying reliable differences at
      rest between high- and low-transliminality individuals would support a
      predisposition for transliminality-related traits. Individuals high in
      transliminality exhibited lower alpha, beta, and gamma power than individuals low
      in transliminality over left posterior association cortex and lower high alpha,
      low beta, and gamma power over the right superior temporal region. In contrast,
      when compared to individuals low in transliminality, individuals high in
      transliminality exhibited greater gamma power over the frontal-midline region.
      These results are consistent with prior research reporting reductions in left
      temporal/parietal activity, as well as the desynchronization of right temporal
      activity in schizotypy and related schizophrenia spectrum disorders. Further,
      differences between high- and low-transliminality groups extend existing theories
      linking altered hemispheric asymmetries in brain activity to a predisposition
      toward schizophrenia, paranormal beliefs, and unusual experiences.

PMID- 18814872
TI  - Mercury levels and fish consumption practices in women of child-bearing age in
      the Florida Panhandle.
AB  - The southeastern United States, and in particular the coastal areas along the
      Gulf of Mexico (Gulf Coast) in Florida, experience some of the highest levels of
      mercury deposition in the country. Although the State of Florida's coastal border
      is among the longest in the United States, and the State has issued fish
      consumption advisories due to mercury on multiple fish species, few data have
      been systematically collected to assess mercury levels in the human population of
      the state or to assess the efficacy of the consumption advisories. Because of the
      generally high rate of seafood consumption among coastal populations, the human
      population in the Florida Panhandle, near Pensacola, FL is potentially exposed to
      elevated levels of mercury. In the present study, we analyzed hair mercury levels
      in women of child-bearing age (16-49 years) who had resided near Pensacola, FL
      for at least 1 year. We also surveyed the fish consumption practices of the
      cohort and evaluated awareness of the Florida Fish Consumption Advisory. Hair
      mercury levels were significantly higher in women who consumed fish within the 30
      days prior to sampling (p<0.05) and in those women who were unaware of the
      consumption advisory (p<0.05). Only 31% of the women reported knowledge of the
      consumption advisory and pregnant women exhibited lower awareness of the advisory
      than non-pregnant women. The data suggest that public health interventions such
      as education and fish advisories have not reached the majority of women in the
      counties surrounding Pensacola who are most at risk from consumption of fish with
      high levels of mercury.

PMID- 18814873
TI  - Effects of aging and arm swing on the metabolic cost of stability in human
      walking.
AB  - To gain insight into the mechanical determinants of walking energetics, we
      investigated the effects of aging and arm swing on the metabolic cost of
      stabilization. We tested two hypotheses: (1) elderly adults consume more
      metabolic energy during walking than young adults because they consume more
      metabolic energy for lateral stabilization, and (2) arm swing reduces the
      metabolic cost of stabilization during walking in young and elderly adults. To
      test these hypotheses, we provided external lateral stabilization by applying
      bilateral forces (10% body weight) to a waist belt via elastic cords while young
      and elderly subjects walked at 1.3m/s on a motorized treadmill with arm swing and
      with no arm swing. We found that the external stabilizer reduced the net rate of
      metabolic energy consumption to a similar extent in elderly and young subjects.
      This reduction was greater (6-7%) when subjects walked with no arm swing than
      when they walked normally (3-4%). When young or elderly subjects eliminated arm
      swing while walking with no external stabilization, net metabolic power increased
      by 5-6%. We conclude that the greater metabolic cost of walking in elderly adults
      is not caused by a greater cost of lateral stabilization. Moreover, arm swing
      reduces the metabolic cost of walking in both young and elderly adults likely by
      contributing to stability.

PMID- 18814874
TI  - Simultaneous separation of inorganic anions and metal-citrate complexes on a
      zwitterionic stationary phase with on-column complexation.
AB  - The retention and separation selectivity of inorganic anions and on-column
      derivatised negatively charged citrate or oxalate metal complexes on reversed
      phase stationary phases dynamically coated with N-(dodecyl-N,N
      dimethylammonio)undecanoate (DDMAU) has been investigated. The retention
      mechanism for the metal-citrate complexes was predominantly anion exchange,
      although the amphoteric/zwitterionic nature of the stationary phase coating
      undoubtedly also contributed to the unusual separation selectivity shown. A
      mixture of 10 inorganic anions and metal cations was achieved using a 20 cm
      monolithic DDMAU modified column and a 1 mM citrate eluent, pH 4.0, flow rate
      equal to 0.8 mL/min. Selectivity was found to be strongly pH dependent, allowing
      additional scope for manipulation of solute retention, and thus application to
      complex samples. This is illustrated with the analysis of an acidic mine drainage
      sample with a range of inorganic anions and transition metal cations, varying
      significantly in their concentrations levels.

PMID- 18814875
TI  - Droplet-based microdialysis-Concept, theory, and design considerations.
AB  - The capability of continuously sampling the extracellular fluid opens up a wide
      range of applications of microdialysis in biological, pharmaceutical, and
      clinical studies. Existing microdialysis, however, faces challenges in sampling
      analytes with fast clearance and limited diffusivity because sampling resolution
      is limited by device size. Size reduction in probes and interconnected cannulae
      is a promising solution to improve temporal and spatial resolution. But the back
      pressure produced by resistance to laminar flows will be magnified in smaller
      channels, raising a concern as to whether it is feasible to operate continuous
      perfusion for miniaturized microdialysis. We demonstrate that a 10-fold smaller
      channel will exhibit 100-fold larger back pressure in response to the increase in
      the flow rate to maintain the relative recovery. In order to overcome the
      foreseen back pressure issue, this paper discusses a new concept using discrete
      droplets instead of continuous flows to operate dialysis in a miniaturized probe.
      This conceptual design is referred to as droplet-based digital microdialysis, in
      which droplets are produced, controlled and advanced within microchannels at a
      rate that in theory should allow for analytes to equilibrate with the
      extracellular fluid under no flow conditions. Expecting that a digital droplet
      design will entirely eliminate back pressure by introducing air between droplets,
      we numerically compare the equilibration kinematics of droplets to that of
      continuous flow. Results suggest equilibration of low molecular weight analytes
      between intermittently stationary droplets and the extracellular fluid in a few
      seconds. Considerations in design, prototyping, calibration and quantification,
      and the integration with other devices are suggested.

PMID- 18814876
TI  - Quality control of flavonoids in Ginkgo biloba leaves by high-performance liquid
      chromatography with diode array detection and on-line radical scavenging activity
      detection.
AB  - Flavonoids in plants used for the treatment of various cardiovascular, cancer
      diseases have been reported to possess potential protective effects against
      oxidative injury. Ginkgo biloba leaves, known for their antioxidant activity,
      were chosen for this study. In this paper, 12 flavonoids in G. biloba leaves were
      identified by HPLC-diode array detection (DAD)-electrospray ionization MS. HPLC
      DAD coupled with chemiluminescence detection was used to determine free radical
      scavenging activity of flavonoids. It was found that the flavonol glycosides
      could markedly inhibit the luminescent signal, which indicated that they are
      mainly responsible for the antioxidant activities of G. biloba leaves. Total
      antioxidant activity of these flavonoids was used to evaluate the differences of
      G. biloba leaves collected in 13 habitats. The combination of chemical and
      activity analysis can provide a valid method to quantify the bioactive components
      in G. biloba leaves, and this may be a more rational approach to the quality
      assessment of G. biloba leaves.

PMID- 18814877
TI  - Optimization of the single-step synthesis of hybrid C(8) silica monoliths
      dedicated to nano-liquid chromatography and capillary electrochromatography.
AB  - Hybrid silica monoliths functionalized with octyl groups and dedicated to
      chromatographic separations in the reversed-phase mode were directly synthesized
      within capillaries according to the protocol described by Yan et al. [L.J. Yan,
      Q.H. Zhang, Y.Q. Feng, W.B. Zhang, T. Li, L.H. Zhang, Y.K. Zhang, J. Chromatogr.
      A 1121 (2006) 92]. Although these monoliths allowed reaching high efficiencies in
      capillary electrochromatography (CEC), serious limitations prohibited their
      application in nano-liquid chromatography (nano-LC). Such limitations observed as
      poor performances in the nano-LC mode and the lack of reproducibility of the
      synthesis were related to the longitudinal morphological inhomogeneities of the
      hybrid material along the capillary. Thus, several modifications were conducted
      in the synthesis protocol in order to improve the resulting morphology of the
      monolith making it suitable for nano-LC separations. The influence of several
      critical parameters (such as the addition temperature of the basic catalyst and
      the hydrolysis duration) on the textural and chromatographic properties had been
      extensively studied. It was found that a decrease (i.e. 0 degrees C) of the
      temperature addition of the basic catalyst associated with a shorter hydrolysis
      duration (1h instead of 6h) allowed (i) delaying the gelation time and
      consequently facilitating the capillary filling step, (ii) increasing the
      structural homogeneity of the hybrid monoliths, i.e. their chromatographic
      performances in nano-liquid chromatography also (iii) greatly improving the
      reproducibility of the synthesis within the capillary without impairing the
      material's carbon load, i.e. the incorporation of the less hydrolysable C(8)
      precursor. The resulting hybrid monoliths afforded retention factors comparable
      to that previously obtained for C(18) grafted silica monoliths and efficiencies
      that are the best ever recorded in nano-LC with hybrid monoliths and that are
      close to the ones achieved with grafted silica monoliths. In fact, this modified
      protocol allowed a significant improvement of the performances in nano-LC which
      could be observed by the decrease of the mean value of H(min) going from 123
      microm (Yan's protocol) to 24 microm (modified protocol) for a same length of
      capillary (l = 8.5 cm). In addition, the reproducibility of the synthesis was
      greatly improved through a factor six of reduction on the calculated standard
      deviation of these efficiencies. The high permeability and longitudinal
      homogeneity of the synthesized monolith allowed increasing the capillary length
      (for example, a 75-cm capillary was conveniently filled with hybrid silica
      monolith) and the column could be eluted at a very low backpressure leading to
      chromatographic performances up to 40,000 plates. Finally, the good efficiencies
      in the nano-LC mode combined with the excellent performances already present in
      the CEC mode led to fast (less than 1 min) and high efficient separations in the
      pressurized capillary electrochromatography (p-CEC) mode.

PMID- 18814878
TI  - Matrix solid-phase dispersion extraction of carbadox and olaquindox in feed
      followed by hydrophilic interaction ultra-high-pressure liquid chromatographic
      analysis.
AB  - A new method involving matrix solid-phase dispersion (MSPD) extraction and
      hydrophilic interaction ultra-high-pressure liquid chromatography (HILIC-UHPLC)
      with photodiode array detection was developed for the determination of carbadox
      and olaquindox in feed. Separation of carbadox and olaquindox was achieved within
      1 min on the 1.7 microm Acquity UPLC BEH HILIC column by using isocratic elution
      with a mobile phase consisting of 10 mmol L(-1) ammonium acetate in acetonitrile
      water (95:5, v/v) at a flow rate of 0.5 mL min(-1). Optimization of MSPD
      extraction parameters, such as type of solid sorbent and elution solvent were
      carried out. Optimal conditions selected for MSPD extraction were: 0.25 g of feed
      sample, 0.5 g of octadecylsilica as solid sorbent and 10 mL of acetonitrile
      methanol (8:2, v/v) as eluting solvent. Both analytes provided average recoveries
      from spiked feed samples ranging from 89.1 to 98.4% with relative standard
      deviations less than 10%. Obtained performance characteristics are comparable to
      those achieved by liquid-liquid extraction-HPLC with the advantages of being
      simpler and significantly faster.

PMID- 18814879
TI  - Supercritical fluid extraction of aflatoxin B(1) from soil.
AB  - This research describes the development of a supercritical fluid extraction (SFE)
      method to recover aflatoxin B(1) from fortified soil. The effects of temperature,
      pressure, modifier (identity and percentage), and extraction type were assessed.
      Using the optimized SFE conditions, the mean recovery from air dried soil was
      72%. The variables associated with changes in recovery of aflatoxin were co
      solvents, static extraction, and temperature. Acetonitrile-2% acetic acid, used
      both in-cell and on-line, provided the most efficient recovery. The results
      indicate that desorption from the soil was the limiting factor in recovery and
      that the static phase was more important than the dynamic.

PMID- 18814880
TI  - Application of an improved proteomics method, fluorogenic derivatization-liquid
      chromatography-tandem mass spectrometry, to differential analysis of proteins in
      small regions of mouse brain.
AB  - To identify age-related proteins in small regions of mouse brain, we improved a
      proteomics approach, fluorogenic derivatization-liquid chromatography-tandem mass
      spectrometry (FD-LC-MS/MS), and applied the method to the differential proteome
      analysis of aging in cerebral cortex, hippocampus and brainstem. The method
      showed good accuracy with RSDs <10% for between-day protein peak heights, and
      much better sensitivity for the detection of proteins compared to other
      proteomics approaches. The existence of 28 regionally specific age-related
      proteins in mouse brain was demonstrated. These results verified that the small
      brain regions could be the targets for proteome analysis by the FD-LC-MS/MS
      method.

PMID- 18814881
TI  - Cold fiber solid-phase microextraction device based on thermoelectric cooling of
      metal fiber.
AB  - A new cold fiber solid-phase microextraction device was designed and constructed
      based on thermoelectric cooling. A three-stage thermoelectric cooler (TEC) was
      used for cooling a copper rod coated with a poly(dimethylsiloxane) (PDMS) hollow
      fiber, which served as the solid-phase microextraction (SPME) fiber. The copper
      rod was mounted on a commercial SPME plunger and exposed to the cold surface of
      the TEC, which was enclosed in a small aluminum box. A heat sink and a fan were
      used to dissipate the generated heat at the hot side of the TEC. By applying an
      appropriate dc voltage to the TEC, the upper part of the copper rod, which was in
      contact to the cold side of the TEC, was cooled and the hollow fiber reached a
      lower temperature through heat transfer. A thermocouple was embedded in the cold
      side of the TEC for indirect measurement of the fiber temperature. The device was
      applied in quantitative analysis of off-flavors in a rice sample. Hexanal,
      nonanal, and undecanal were chosen as three off-flavors in rice. They were
      identified according to their retention times and analyzed by GC-flame ionization
      detection instrument. Headspace extraction conditions (i.e., temperature and
      time) were optimized. Standard addition calibration graphs were obtained at the
      optimized conditions and the concentrations of the three analytes were
      calculated. The concentration of hexanal was also measured using a conventional
      solvent extraction method (697+/-143ng/g) which was comparable to that obtained
      from the cold fiber SPME method (644+/-8). Moreover, the cold fiber SPME resulted
      in better reproducibility and shorter analysis time. Cold fiber SPME with TEC
      device can also be used as a portable device for field sampling.

PMID- 18814882
TI  - Effect of n-octanol in the mobile phase on lipophilicity determination by
      reversed-phase high-performance liquid chromatography on a modified silica
      column.
AB  - In this study, we show that the addition of n-octanol to the mobile phase
      improves the chromatographic determination of lipophilicity parameters of
      xenobiotics (neutral solutes, acidic, neutral and basic drugs) on a Phenomenex
      Gemini C18 column. The Gemini C18 column is a new generation hybrid silica-based
      column with an extended pH range capability. The wide pH range (2-12) afforded
      the examination of basic drugs and acidic drugs in their neutral form.
      Extrapolated retention factor values, [Formula: see text] , obtained on the above
      column with the n-octanol-modified mobile phase were very well correlated (1:1
      correlation) with literature values of logP (logarithm of the partition
      coefficient in n-octanol/water) of neutral compounds and neutral drugs (69). In
      addition, we found good linear correlations between measured [Formula: see text]
      values and calculated values of the logarithm of the distribution coefficient at
      pH 7.0 (logD(7.0)) for ionized acidic and basic drugs (r(2)=0.95). The Gemini C18
      phase was characterized using the linear solvation energy relationship (LSER)
      model of Abraham. The LSER system constants for the column were compared to the
      LSER constants of n-octanol/water extraction system using the Tanaka radar plots.
      The comparison shows that the two methods are nearly equivalent.

PMID- 18814883
TI  - Improved method for fatty acid analysis in herbage based on direct
      transesterification followed by solid-phase extraction.
AB  - Direct transesterification (DT) and solvent extraction with acid or basic
      derivatization procedure for fatty acid (FA) analysis in herbage were compared.
      The highest total FA, alpha-linolenic and linoleic acid contents were obtained
      with DT. However, DT also produced the highest amount of interfering compounds,
      identified as phytadienes and sugar derivative products, which may co-elute with
      FA. An additional step based on solid-phase extraction to produce clean samples
      was proposed. This procedure is simple and gives good recoveries for the FA
      fortified samples. Additionally, structural characterization of 16:1 trans-3 was
      conducted by covalent adduct chemical ionization tandem mass spectrometry.

PMID- 18814884
TI  - Expression of platelet-derived growth factor-beta receptor and bovine
      papillomavirus E5 and E7 oncoproteins in equine sarcoid.
AB  - Equine sarcoids are benign fibroblastic skin tumours that are recognized
      throughout the world. Infection with bovine papillomavirus (BPV) types 1 and 2
      has been implicated as a major factor in disease development; however, the
      cellular mechanisms underlying fibroblast transformation remain poorly defined.
      The present study further characterizes aspects of the association with BPV in 15
      equine sarcoids. BPV DNA was demonstrated in 12/15 tumours collected from
      different areas of Italy. Nine of these 12 tumours expressed the BPV oncoproteins
      E5 and E7, but these oncoproteins were not expressed by normal equine cells. The
      BPV E5 protein is known to bind to the platelet-derived growth factor-beta
      receptor (PDGF-betaR) and this molecule was expressed by 11 of the 12 sarcoids in
      which E5 was demonstrated. These findings add further weight to the theory that
      BPV and the PDGF-betaR may have a role in the pathogenesis of this disease.

PMID- 18814885
TI  - Hypertensive diseases of pregnancy and the development of behavioral problems in
      childhood and adolescence: the Western Australian Pregnancy Cohort Study.
AB  - OBJECTIVE: To examine whether maternal gestational hypertension and preeclampsia
      are associated with behavioral problems in offspring throughout childhood and
      early adolescence. STUDY DESIGN: We conducted a prospective cohort study of 2804
      women in the Western Australian Pregnancy Cohort Study and their children
      observed at age 2, 5, 8, 10, and 14 years. The Child Behavior Checklist (CBCL)
      was used to measure problem child behavior with continuous z-scores and clinical
      cutoff points. Control variables included known biomedical, sociodemographic, and
      psychological factors. RESULTS: After adjustment, with general linear model
      analyses children of women with gestational hypertension were shown to be more
      likely to have higher CBCL z-scores, indicative of poorer behavior, from 8 years
      on, with the largest difference seen at 14 years. Children of mothers with
      preeclampsia were more likely to have lower CBCL z-scores, indicative of pro
      social behaviors. The multivariable logistic regression analysis showed that
      gestational hypertension was predictive of clinically significant CBCL T-scores
      from age 8 to 14 years. This association was significant for externalizing
      behavior, such as delinquent and aggressive behavior, and for internalizing
      behavior at age 14 years. Unexpectedly, preeclampsia reduced internalizing
      morbidity at ages 5 and 8 years. CONCLUSIONS: The opposing effect on child and
      adolescent behavior of gestational hypertension and preeclampsia warrants further
      attention.

PMID- 18814886
TI  - Retrospective study of the potential benefits and adverse events during growth
      hormone treatment in children with Prader-Willi syndrome.
AB  - OBJECTIVE: To assess the effectiveness of growth hormone (GH) treatment of
      children with Prader-Willi syndrome (PWS) in clinical practice. STUDY DESIGN:
      This was a review of 23 patients with PWS (14 males, 9 females) under age 18
      years, 10 of whom (5 males, 5 females) had been treated with GH for periods
      between 0.1 and 5.5 years. All of these patients had a GH level < 5.5 microg/L on
      2 GH stimulation tests. RESULTS: In the 8 patients treated with GH for more than
      1 year, median height velocity was 8.6 cm/year (range, 2.0 to 14.5 cm/year)
      during the first year, greater than that in the no-GH group (5.5 cm/year [range,
      0.8 to 7.0 cm/year]) (P < .05). The evolution of body mass index (BMI) was
      similar in both groups, however (GH group: 3.1 standard deviation score [SDS;
      range, -2.5 to +6.7] at GH initiation and 3.3 SDS [range, -0.4 to +8.9] at last
      visit; no-GH group: 3.2 SDS [range, -0.3 to +6.4] at first visit and 2.6 SDS
      [range, -0.1 to +6.4] at last visit). In 3 patients treated with GH, sequential
      body composition analysis by dual-energy X-ray absorptiometry revealed no
      benefit. In both groups, stabilization or diminution of BMI was more often
      observed in children of highly educated parents. Two of the 10 patients treated
      with GH developed obstructive sleep apnea (OSA) 1 to 2 months after starting GH,
      1 of whom died (reported previously). CONCLUSIONS: GH therapy in children with
      PWS in the clinical setting did not lead to any discernible improvement in BMI or
      body composition and appeared to be associated with OSA. Regardless of GH
      therapy, parental education was associated with better outcome.

PMID- 18814887
TI  - A randomized, controlled trial of the impact of early and rapid diagnosis of
      viral infections in children brought to an emergency department with febrile
      respiratory tract illnesses.
AB  - OBJECTIVES: Acute respiratory tract infections represent a significant burden on
      pediatric emergency departments (ED) and families. We hypothesized that early and
      rapid diagnosis of a viral infection alleviates the need for ancillary testing
      and antibiotic treatment. STUDY DESIGN: We conducted a randomized, controlled
      trial of children 3 to 36 months of age with febrile acute respiratory tract
      infections at a pediatric ED. Two hundred four subjects were randomly assigned to
      receive rapid respiratory viral testing on admission or a routine ED admission
      protocol. Outcome measures were: mean length of visits, rate of ancillary tests,
      and antibiotic prescription in the ED. A follow-up call was made to all study
      subjects to inquire about further healthcare visits, ancillary testing, and
      antibiotic prescription after ED discharge. RESULTS: We did not find a
      statistically significant difference in ED length of visits, rate of ancillary
      testing, or antibiotic prescription rate in the ED between the study groups.
      There was, however, a significant reduction in antibiotic prescription after ED
      discharge (in the group who had rapid viral testing RR = 0.36; 95% CI = 0.14,
      0.95). CONCLUSIONS: Rapid multi-viral testing in the ED did not significantly
      affect ED patient treatment but may reduce antibiotic prescription in the
      community after discharge from the ED, suggesting a novel strategy to alter
      community physician antibiotic prescription patterns.

PMID- 18814888
TI  - Cellular remyelinating therapy in multiple sclerosis.
AB  - Demyelination is a pathological hallmark of multiple sclerosis (MS), a chronic
      autoimmune disorder of the central nervous system (CNS) that affects mainly young
      people in western countries. Recent studies have shown that remyelination can be
      accomplished by supplying demyelinated regions with myelinogenic cells or neural
      stem cells via transplantation. The remyelinating effect of these cells may be
      via one or more mechanisms, including: 1) as an immunomodulator by producing
      soluble factors; 2) direct cell replacement by differentiating into neural and
      glial cells in the lesion; and 3) indirect action by promoting neural and glial
      differentiation of endogenous cells. Identifying these mechanisms will help in
      choosing an optimal and more effective approach for cell-based therapy. Here we
      present a brief view focusing on myelin-forming cell types that can be used for
      cell transplantation and draw on a variety of recent experimental findings to
      speculate on the likely future evolution of remyelinating therapies.

PMID- 18814889
TI  - Levodopa/carbidopa/entacapone-induced acute Pisa syndrome in a Parkinson's
      disease patient.
AB  - Pisa syndrome (PS) is a dystonic lateroflexion of the trunk with a postural
      disturbance resembling the leaning tower of Pisa. Initially reported as a side
      effect related to antipsychotic therapy, this original dystonic posture is also
      manifested in neurodegenerative disorders such as Alzheimer's disease and
      multiple system atrophy, or in rare idiopathic cases. Recent observations have
      described the onset of PS with subchronic course in patients affected by
      Parkinson's disease (PD). Here, we report on the acute development of PS in a
      parkinsonian patient during treatment with entacapone/levodopa/carbidopa
      combination. This case illustrates how, in contrast to previously well-known
      chronic/subchronic forms, this axial dystonic posture may occur in PD as an acute
      onset reversible type, related to levodopa treatment.

PMID- 18814890
TI  - Methane and nitrous oxide fluxes in the polluted Adyar River and estuary, SE
      India.
AB  - We measured dissolved N(2)O, CH(4), O(2), NH(4)(+), NO(3)(-) and NO(2)(-) on 7
      transects along the polluted Adyar River-estuary, SE India and estimated N(2)O
      and CH(4) emissions using a gas exchange relation and a floating chamber. High
      NO(2)(-) implied some nitrification of a large anthropogenic NH(4)(+) pool. In
      the lower catchment CH(4) was maximal (6.3+/-4.3 x 10(4)nM), exceeding the
      ebullition threshold, whereas strong undersaturation of N(2)O and O(2) implied
      intense denitrification. Emissions fluxes for the whole Adyar system
      approximately 2.5 x 10(8) g CH(4)yr(-1) and approximately 2.4 x 10(6)gN(2)O yr(
      1) estimated with a gas exchange relation and approximately 2 x 10(9) g CH(4)yr(
      1) derived with a floating chamber illustrate the importance of CH(4) ebullition.
      An equivalent CO(2) flux approximately 1-10 x 10(10)gy r(-1) derived using global
      warming potentials is equivalent to total Chennai motor vehicle CO(2) emissions
      in one month. Studies such as this may inform more effective waste management and
      future compliance with international emissions agreements.

PMID- 18814891
TI  - Consequences of spring phytodetritus sedimentation on the benthic compartment
      along a depth gradient in the Eastern English Channel.
AB  - Phaeocystis blooms are of major importance in the Eastern English Channel, where
      they significantly contribute to spring organic matter input with chlorophyll
      concentrations commonly higher than 30 microgl(-1) in the water column. Post
      bloom deposition of Phaeocystis derived mucilaginous compounds has been shown to
      have a major importance on benthic intertidal systems, but resulting
      mineralization processes and consequences on the macrobenthic compartment remain
      poorly documented in subtidal areas. In this frame, a study was performed along
      the French coast of the English Channel to quantify mineralization processes, as
      well as potential consequences on subtidal sediments, especially their
      geochemistry and associated macrofaunal communities. Seven stations were studied
      along a depth gradient during four cruises: before (March), during (April, May)
      and after (June) the spring bloom. Sediment characteristics and organic carbon
      content were described, as well as sediment-water fluxes of oxygen and ammonium.
      Macrofaunal characteristics were also analyzed. Stations were chosen as
      representative of the various benthic communities present in the area, which are
      directly linked to the granulometric characteristics of the sediments. To account
      for the general functioning of the water column, characterized by a coastal flow
      where higher concentrations of Phaeocystis are generally recorded, similar
      communities were sampled inshore and offshore, when possible: (i) the Abra alba
      community located only close to the coast, (ii) the Ophelia borealis community
      located inshore and offshore, and (iii) the Amphioxus lanceolatus community
      located inshore and offshore. Generally, low exchange rates of oxygen and
      ammonium were measured (respectively, in the range 50-150 micromol O2 m(-2)h(-1)
      and -25 to 35 micromol NH4+ m(-2)h(-1)) between the water column and the muddy
      sand to coarse sand permeable sediments, as a consequence of the low organic
      carbon content due to the high hydrodynamic forcing. As a consequence of organic
      matter accumulation in surficial sediments probably resulting from Phaeocystis
      post-bloom deposition, an increase of sediment oxygen demand and ammonium release
      was clearly evidenced up to 660 micromol O2 m(-2)h(-1) and 205 micromol NH4+ m(
      2)h(-1) in May, only in stations located close to the coast (<8 kms), in the A.
      alba community. Despite those significant biogeochemical changes in surficial
      sediments, no significant consequence was pointed out on macrofauna, neither in
      the O. borealis and A. lanceolatus communities, nor in the coastal A. alba
      community. Most of the temporal variations recorded might be attributed to the
      common spring population dynamics, but this study highlights the potential use of
      geochemical parameters as a forewarning signal of benthic disequilibrium.

PMID- 18814892
TI  - Diagnostic validity of an expert tuberculosis commission that assists the
      diagnosis of bacteriologically negative suspected TB cases in Havana, Cuba.
AB  - The Provincial Tuberculosis Commission of Havana, Cuba, a multi-speciality
      committee, assists clinicians in diagnosing bacteriologically negative
      tuberculosis (TB). At its weekly meetings, clinicians present the files of
      suspected TB cases for discussion, diagnosis and recommendations. This
      prospective study assessed the validity of the diagnoses made by the Commission
      by comparing the diagnoses made with diagnoses ascertained after one year of
      follow-up. Between October 2002 and December 2003, 126 patients suspected to have
      TB but who were bacteriologically negative completed diagnostic work at the
      Commission. Fifty-three (42%) were diagnosed as TB cases. The definite diagnosis
      of 116 patients (92%) was ascertained after one year of follow-up. Six patients
      diagnosed by the Commission as TB cases were suffering from other diseases, while
      one patient diagnosed with pneumonia had a definite diagnosis of pulmonary TB.
      The diagnostic sensitivity and specificity of the Commission were 98% (95% CI 93
      100) and 92% (95% CI 85-98), respectively. The Provincial Tuberculosis Commission
      of Havana can be considered a valuable tool for the diagnosis of TB in patients
      suspected of TB but who are bacteriologically negative. A comparable approach,
      adapted to the local conditions, could prove useful in other epidemiological and
      healthcare settings.

PMID- 18814893
TI  - Cytokines in central nervous system trypanosomiasis: cause, effect or both?
AB  - The late, or encephalitic, stage of human African trypanosomiasis (HAT), or
      sleeping sickness, is typified by a diffuse meningoencephalitis characterised
      neuropathologically by perivascular infiltration of inflammatory cells. While the
      cause of this neuroinflammatory reaction is not understood, there is evidence for
      the roles of pro-inflammatory cytokines such as IFN-gamma and TNF-alpha and
      counter-inflammatory cytokines such as IL-10, with the balance of these
      influencing disease outcome. Because of the practical difficulties of obtaining
      serial measurements in patients, it has proved difficult to assign either cause
      or effect properties to measured cytokines, but mechanistic animal modelling
      studies are proving helpful.

PMID- 18814894
TI  - High latrine coverage is not reducing the prevalence of soil-transmitted
      helminthiasis in Hoa Binh province, Vietnam.
AB  - A baseline epidemiological survey for parasite infections was conducted between
      December 2007 and January 2008 in 155 villagers in a rural commune in Hoa Binh
      province, Vietnam. The prevalence of Ascaris lumbricoides, Trichuris trichiura
      and hookworm infection was 13.5%, 45.2% and 58.1%, respectively. At least one of
      the parasites was detected in 72.3% of the samples. We found no association
      between infection with A. lumbricoides or T. trichiura and engagement in
      agriculture, while hookworm infection was more prevalent in populations having
      frequent contact with soil. Agricultural use of human faeces was not correlated
      with any of the infections. We suggest that the consumption of vegetables that
      are commonly fertilized with human faeces in the community has led to the high
      infection rates with A. lumbricoides and T. trichiura, rather than the
      manipulation of faeces in farming activity. This also explains the high infection
      prevalence, despite high latrine coverage (98.1%) in the study population. The
      presence of latrines alone is not sufficient to reduce the prevalence of
      helminthiasis in a rural agricultural community if fresh faeces are used as
      fertilizer.

PMID- 18814895
TI  - Costs and performance of early hearing detection programmes in Lagos, Nigeria.
AB  - In line with global progress towards early detection of permanent congenital and
      early-onset hearing loss (PCEHL), the costs and performance of hospital-based and
      community-based infant hearing screening models were evaluated in Lagos, Nigeria.
      The protocol consisted of two-stage screening with transient-evoked otoacoustic
      emissions and automated auditory brainstem response followed by diagnostic
      evaluation for all infants referred after the second-stage screening. The main
      outcome measures were referral rates at screening, cost per baby screened, cost
      per case detected and yield for PCEHL. First-stage referrals were 32.2% for
      universal and 31.7% for targeted screening in the hospital, compared with 14.3%
      and 15.2%, respectively for the community-based programme. Second-stage referrals
      ranged from 3.3% under hospital-based universal screening to 4.9% under community
      based targeted screening. The highest yields of 27.4 and 22.5 per 1000 were
      recorded under community-based targeted and universal screening, respectively.
      Screening cost per child was lowest (US$7.62) under community-based universal
      screening and highest (US$73.24) under hospital-based targeted screening.
      Similarly, cost per child detected with PCEHL was lowest (US$602.49) for
      community-based universal screening and highest (US$4631.33) for hospital-based
      targeted screening. Community-based universal screening of infants during routine
      immunisation clinics appears to be the most cost-effective model for early
      detection of PCEHL in low-income countries.

PMID- 18814896
TI  - Importance of cholesterol-rich membrane microdomains in the interaction of the S
      protein of SARS-coronavirus with the cellular receptor angiotensin-converting
      enzyme 2.
AB  - Cholesterol present in the plasma membrane of target cells has been shown to be
      important for the infection by SARS-CoV. We show that cholesterol depletion by
      treatment with methyl-beta-cyclodextrin (m beta CD) affects infection by SARS-CoV
      to the same extent as infection by vesicular stomatitis virus-based pseudotypes
      containing the surface glycoprotein S of SARS-CoV (VSV-Delta G-S). Therefore, the
      role of cholesterol for SARS-CoV infection can be assigned to the S protein and
      is unaffected by other coronavirus proteins. There have been contradictory
      reports whether or not angiotensin-converting enzyme 2 (ACE2), the cellular
      receptor for SARS-CoV, is present in detergent-resistant membrane domains. We
      found that ACE2 of both Vero E6 and Caco-2 cells co-purifies with marker proteins
      of detergent-resistant membranes supporting the notion that cholesterol-rich
      microdomains provide a platform facilitating the efficient interaction of the S
      protein with the cellular receptor ACE2. To understand the involvement of
      cholesterol in the initial steps of the viral life cycle, we applied a cell-based
      binding assay with cells expressing the S protein and cells containing
      angiotensin-converting enzyme 2 (ACE2). Alternatively, we used a soluble S
      protein as interaction partner. Depletion of cholesterol from the ACE2-expressing
      cells reduced the binding of S-expressing cells by 50% whereas the binding of
      soluble S protein was not affected. This result suggests that optimal infection
      requires a multivalent interaction between viral attachment protein and cellular
      receptors.

PMID- 18814897
TI  - Molecular and structural characterization of HIV-1 subtype B Brazilian isolates
      with GWGR tetramer at the tip of the V3-loop.
AB  - One of most intriguing features of the HIV-1 subtype B epidemic in Brazil is the
      high frequency of isolates exhibiting tryptophan (W) in the tetramer (GWGR) at
      the tip of the V3 loop. We observed that the frequencies of glutamic and aspartic
      acids at site 25 of the V3 loop are quite distinct in GWGR isolates compared with
      viruses with other tetramers. The basic amino acids at sites 11 and 25 of V3 are
      strongly linked with CCR5-to-CXCR4 coreceptor shift. We therefore predicted
      phenotype usage and found that GWGR isolates are exclusively CCR5-using. Further
      evidence of this came from intrahost sequences, where basic amino acid
      substitutions at sites 11 and 25 emerged only in isolates presenting a tryptophan
      to-glycine replacement at the tetramer of the V3. In addition, modeled 3D
      structures of the V3 loop of GWGR and GGGR in intrahost viruses differ
      essentially in the binding region of the coreceptor.

PMID- 18814898
TI  - Fate of a branched nonylphenol isomer in submerged paddy soils amended with
      nitrate.
AB  - Using a (14)C-labelled branched isomer of NP, the fate of NP was studied in two
      flooded typical paddy soils under anoxic conditions. Biodegradation of NP
      occurred under anoxic conditions and was accompanied by the production of polar
      metabolites and bound residues in alkaline soil extract and humin. The addition
      of nitrate (20mM) increased the degradation of NP in both soils, especially in
      soil derived from silt loam deposit, which contained high amounts of organic
      matter. Less than 1% NP mineralization was detected as free CO(2) in both soils,
      whereas up to 30, 21, 31% of NP residues comprised at least two polar
      metabolites, those extractable from humic substances and from the humin fraction,
      respectively. The denaturing gradient gel electrophoresis (DGGE) analysis of DNA
      extract of the soil microorganisms hinted differences of microbial community
      between soils with different degradation rates of NP. The present study provides
      for the first time information about the fate of a branched nonylphenol isomer in
      submerged soils amended with nitrate. The production of high amounts of polar
      metabolites under anoxic conditions suggests the necessity of also considering
      the fate and possible effects of the degradation products of NP in anoxic
      environment such as in waterlogged soil.

PMID- 18814899
TI  - Photocatalytic degradation of Acid Red 4 using a titanium dioxide membrane
      supported on a porous ceramic tube.
AB  - A photocatalytic membrane supported on a porous ceramic tube was described, in
      which permeation of solutes through the membrane and tube and photocatalytic
      reaction occur simultaneously. In this photocatalytic membrane reactor, TiO(2)
      catalyst was coated on the surface of a porous ceramic tube and all experiments
      were conducted in one pass dead-end system. The objectives of this study are to
      demonstrate the predominance of dead-end operation and to determine the reaction
      kinetics model of the photocatalytic reaction. Acid Red 4 (AR 4) dye was used as
      a model pollutant. A detailed study of physical parameters including flow
      configurations (dead-end and cross-flow), flow rate, initial dye concentration,
      light intensity and catalyst loading has been performed to obtain the reaction
      kinetics. The simultaneous effect of light intensity and catalyst loading was
      also determined experimentally. Experiments were also conducted to compare the
      photocatalytic degradation of AR 4 in the dead-end and cross-flow system. The
      major findings of this study are: (1) the decomposition ratios for dead-end
      system were three and five times higher than cross-flow system at flow rates of
      6.67x10(-8) and 4.00x10(-7)m(3)/s, respectively. (2) The decomposition ratio
      increased with increasing catalyst loading and light intensity, but remained
      constant at higher catalyst loading. (3) The decomposition ratio was found to be
      decreased with increasing flow rate.

PMID- 18814900
TI  - Treatment of PAHs in contaminated soil by extraction with aqueous DNA followed by
      biodegradation with a pure culture of Sphingomonas sp.
AB  - The biodegradation of polycyclic aromatic hydrocarbons (PAHs) in aqueous
      deoxyribonucleic acid (DNA) solution from contaminated soil washing was
      investigated. Initial data with a model effluent consisting of anthracene,
      phenanthrene, pyrene and benzo[a]pyrene that were individually dissolved in 1%
      aqueous DNA solution confirmed their positive degradation by Sphingomonas sp. at
      around 10(8)CFU mL(-1) initial cell loading. For anthracene and phenanthrene,
      complete removal was achieved within 1h treatment. Degradation of pyrene and
      benzo[a]pyrene took a relatively longer time of a few days and weeks,
      respectively. DNA-dissolved PAHs were also degraded relatively faster than PAH
      crystals in aqueous medium to suggest that the binding of the PAHs in the polymer
      does not pose serious constraint to bacterial uptake. The DNA was stable against
      the PAH-degrading bacteria. Parallel experiments with actual DNA solutions
      obtained during pyrene extraction from an artificially spiked soil also showed
      similar results. Close to 100% pyrene degradation was achieved after 1d
      treatment. With its chemical stability, the cell-treated DNA was re-used up to
      four cycles without a considerable decline in extraction performance.

PMID- 18814901
TI  - Concentrations and fluxes of dissolved organic carbon in UK topsoils.
AB  - Dissolved organic carbon (DOC) concentrations in soil water samples collected
      from depths of 5 to 20 cm at 10 moorland and 11 forest sites during the period
      2000-2006 were obtained from new measurements and from the monitoring programmes
      of the UK Environmental Change Network and the International Cooperative
      Programme (ICP) on Forests. Data on soil properties and vegetation type were also
      assembled. Considering data from Prenart tension collectors, which were used at
      nearly all the sites, mean annual concentrations ranged from 1.3 to 97.5 g m(-3)
      with means of 19.5 (standard deviation 15.2) and 27.6 (SD 23.3) g m(-3) for
      moorland and forest sites respectively. Interannual mean DOC concentration at an
      individual site varied by only 1.5-fold, averaged over all sites with at least
      three years' data. Concentrations during summer months (April to September) were
      on average 17% greater than those in winter (October to March). If data from two
      sites (the single peatland and an unusual forest site) were ignored, DOC
      concentrations were strongly inversely related to water flux, estimated from
      rainfall and evaporation data. Fluxes of DOC, calculated by combining
      concentration with water flux, ranged from 2.2 to 71.9 gC m(-2) yr(-1) over all
      sites and years, with overall means of 19.2 (SD 13.6) and 12.2 (SD 13.9) gC m(-2)
      yr(-1) for the moorland and forest sites respectively. However, if the two
      exceptional sites were omitted, the overall mean was 9.1 gC m(-)(2) yr(-1) with a
      standard deviation of only 4.9 gC m(-2) yr(-1). Annual DOC flux was strongly
      dependent upon annual water flux, varying by 3.5-fold between years when averaged
      over all sites. On average, 75.5% of the DOC was exported during the winter
      period (October to March).

PMID- 18814902
TI  - Priority pollutants in wastewater and combined sewer overflow.
AB  - Implementation of the European Water Framework Directive and its affiliated
      directives requires Member States to improve their understanding of priority
      pollutants (PPs) in urban areas and obviously within wastewater systems. As a
      direct consequence, this study is intended to furnish data on both PP occurrence
      and the significance of concentrations in wastewater during dry and wet periods
      within combined sewers. Various sampling sites within the Paris combined sewer
      network were selected; for each sample, a total of 66 determinants, including
      metals, polycyclic aromatic hydrocarbons (PAHs), pesticides, organotins, volatile
      organic compounds, chlorobenzenes, phthalates and alkylphenols, were analysed. A
      broad range of PPs was observed in wastewater during dry as well as wet weather
      periods. Of the 66 elements investigated, 33 and 40 priority substances could be
      observed in raw sewage and wet weather effluent, respectively. As expected, a
      majority of metals were present in all samples, reflecting their ubiquitous
      nature. For both periods, chlorobenzenes and most of the pesticides always
      remained below the limit of quantification, while the majority of other organic
      pollutants assessed were identified within the microg l(-1) range. As highlighted
      by the larger number of substances detected in wet weather samples and the
      significance of their concentrations, runoff via atmospheric inputs and/or
      surface leaching was found to induce a wider range of PPs (n=40) and lead to
      higher concentrations of certain metals, PAHs, pesticides and other individual
      compounds. The data generated during this survey, which constitutes one of the
      first studies conducted in Europe to report concentrations for a variety of
      priority substances in wastewater within combined sewers, may be used in the
      future to identify PPs of potential significance for dry and wet weather periods
      and targeted for further investigation.

PMID- 18814903
TI  - Point-of-care (POCT) prothrombin time monitors: is a periodical control of their
      performance useful?
AB  - INTRODUCTION: Point-of-care testing (POCT) prothrombin time monitors are now
      widely used to monitor oral anticoagulant treatment. Although portable
      coagulometers are extremely easy to use, checking the quality of their
      performance presents some difficulties. MATERIALS AND METHODS: The aims of this
      study were to investigate on a quarterly basis the performance of 95 Coagucheck S
      assigned to 99 anticoagulated patients at home. This was done checking the
      monitors versus a reference coagulometer in the laboratory at our Thrombosis
      Centre (TC). The other aims were to carry out an external quality assessment
      employing different sets of INR certified plasmas with 5 different ranges of
      anticoagulation and to assess the performance of the different lots of strips
      employed by the patients during the study. RESULTS: No difference between the PT
      INR obtained with both the systems at the first quarterly check was noted but a
      significant difference was found when the two systems were compared at the second
      and third quarterly checks. The Bland-Altman test showed increased disagreement
      between the first and the third controls. The percentage of INR values that
      showed a difference of more or less than 0.5 INR units in the PT values performed
      with both the systems was: 1.0% (first control), 7.5% (second control) and 11.5%
      (third control) (Chi-Square: 8.315, p=0.0156). Lots with differences higher than
      10% in terms of +/- 0.5 INR Units at the first, second and third controls were
      16%, 20.8% and 61%, respectively. Seven monitors (7.3%) failed to test one or two
      of the INR certified plasmas of one set but performed well using a second set of
      plasmas. Three monitors (3.1%) failed to test two sets of plasmas but performed
      well using a different lot of strips (from 279A to 483A). One monitor (1%) gave
      unsatisfactory results with different sets of plasmas and strips. All the other
      PT INR obtained with the monitors fell well within the different ranges of the
      INR certified plasmas. CONCLUSIONS: Anticoagulated patient in self-testing or
      self-management should periodically bring their portable coagulometer to a
      reference Thrombosis Centre especially when the lot of strips have to be changed.
      The role of Thrombosis Centre appears therefore crucial in this regard.

PMID- 18814904
TI  - Comparison of the clinical usefulness of two quantitative D-Dimer tests in
      patients with a low clinical probability of pulmonary embolism.
AB  - BACKGROUND: Quantitative D-Dimer tests are established methods in the non
      invasive diagnostic management to rule out venous thromboembolism (VTE). The
      diagnostic performance and the clinical efficiency different D-Dimer assays in
      the exclusion of pulmonary embolism (PE) have not yet been compared in a clinical
      outcome study. OBJECTIVE: Evaluation of the efficiency and safety of excluding
      the diagnosis of PE with two different quantitative D-Dimer assays in consecutive
      patients with clinically suspected PE. PATIENTS AND METHODS: We studied the VTE
      failure rate of 2206 consecutive patients with an unlikely clinical probability
      in whom VIDAS or Tinaquant D-Dimer tests were performed. RESULTS: The prevalence
      of PE in 1238 patients whose D-Dimer level was analyzed with Tinaquant assay was
      11%. The VIDAS assay group consisted of 968 patients with a PE prevalence of 13%.
      The VIDAS assay had a sensitivity of 99.2% (95%CI; 96- >99.9%), the Tinaquant
      assay of 97.3% (95%CI; 93 -99%). The negative predictive value (NPV) in the
      Tinaquant assay group was 99.4% (95%CI 98-99.8%) in comparison to 99.7% (95%CI 99
      >99.9%) in the VIDAS assay group. During 3 month of follow-up, there were no
      fatal cases of PE among patients with normal D-Dimer and unlikely clinical
      probability in both D-Dimer assay groups. In addition, the test efficiency of
      Tinaquant assay was significantly higher in comparison to VIDAS assay (52% vs
      42%, p<0.001). CONCLUSION: Both Tinaquant and VIDAS D-Dimer tests perform equally
      well in combination with an unlikely clinical probability in excluding PE. The
      Tinaquant test was shown to be more efficient.

PMID- 18814905
TI  - Polymorphisms of tumor necrosis factor alpha gene and coronary heart disease in a
      Chinese Han population: interaction with cigarette smoking.
AB  - INTRODUCTION: Tumor necrosis factor alpha (TNF-alpha) is a primary pro
      inflammatory cytokines and has been implicated in cardiovascular disease
      pathogenesis. Relationship between polymorphisms in TNF-alpha gene and coronary
      heart disease (CHD) has been reported, but remains a controversial one. MATERIALS
      AND METHODS: A single nucleotide polymorphism (SNP) discovery in a total of 4739
      base pairs in the promoter region, exon region and exon/intron boarding region of
      TNF-alpha gene in randomly selected 48 patients by direct sequencing was
      conducted. Four SNPs (-806C>T, -308G>A, -238G>A, and +467G>A) out of seven
      polymorphisms identified were further investigated for associations in 804 CHD
      patients (of which 504 patients with Myocardial infarction (MI)) and 905 age- and
      gender-matched controls. RESULTS: No main effects of loci and haplotypes reached
      statistical significance in the total sample. However, a significant gene-smoking
      interaction was observed. In nonsmokers, compared with individuals of G/G
      genotype, individuals carrying the A allele of the -238G>A polymorphism showed a
      lower risk of developing CHD (odds ratio 0.48, 95%CI 0.24-0.94, P=0.033), and an
      even lower risk of developing MI (odds ratio 0.36, 95%CI 0.15-0.88, P=0.026).
      Haplotype analysis confirmed the results of individual polymorphism analyses. In
      addition, the -806C>T polymorphism was found to be associated with MI in smokers
      (P=0.039). CONCLUSIONS: This study identified a significant interaction between
      TNF-alpha gene and smoking status. Both single locus and haplotype analyses
      indicated that A allele of the -238G>A polymorphism decreased the risk of CHD
      among nonsmokers in Chinese Han population.

PMID- 18814906
TI  - Nasal insulin to prevent type 1 diabetes in children with HLA genotypes and
      autoantibodies conferring increased risk of disease: a double-blind, randomised
      controlled trial.
AB  - BACKGROUND: In mouse models of diabetes, prophylactic administration of insulin
      reduced incidence of the disease. We investigated whether administration of nasal
      insulin decreased the incidence of type 1 diabetes, in children with HLA
      genotypes and autoantibodies increasing the risk of the disease. METHODS: At
      three university hospitals in Turku, Oulu, and Tampere (Finland), we analysed
      cord blood samples of 116 720 consecutively born infants, and 3430 of their
      siblings, for the HLA-DQB1 susceptibility alleles for type 1 diabetes. 17 397
      infants and 1613 siblings had increased genetic risk, of whom 11 225 and 1574,
      respectively, consented to screening of diabetes-associated autoantibodies at
      every 3-12 months. In a double-blind trial, we randomly assigned 224 infants and
      40 siblings positive for two or more autoantibodies, in consecutive samples, to
      receive short-acting human insulin (1 unit/kg; n=115 and n=22) or placebo (n=109
      and n=18) once a day intranasally. We used a restricted randomisation, stratified
      by site, with permuted blocks of size two. Primary endpoint was diagnosis of
      diabetes. Analysis was by intention to treat. The study was terminated early
      because insulin had no beneficial effect. This study is registered with
      ClinicalTrials.gov, number NCT00223613. FINDINGS: Median duration of the
      intervention was 1.8 years (range 0-9.7). Diabetes was diagnosed in 49 index
      children randomised to receive insulin, and in 47 randomised to placebo (hazard
      ratio [HR] 1.14; 95% CI 0.73-1.77). 42 and 38 of these children, respectively,
      continued treatment until diagnosis, with yearly rates of diabetes onset of 16.8%
      (95% CI 11.7-21.9) and 15.3% (10.5-20.2). Seven siblings were diagnosed with
      diabetes in the insulin group, versus six in the placebo group (HR 1.93; 0.56
      6.77). In all randomised children, diabetes was diagnosed in 56 in the insulin
      group, and 53 in the placebo group (HR 0.98; 0.67-1.43, p=0.91). INTERPRETATION:
      In children with HLA-conferred susceptibility to diabetes, administration of
      nasal insulin, started soon after detection of autoantibodies, could not be shown
      to prevent or delay type 1 diabetes.

PMID- 18814907
TI  - Prevention of type 1 diabetes: what next?

PMID- 18814908
TI  - Multifunctional nanocarriers for mammographic quantification of tumor dosing and
      prognosis of breast cancer therapy.
AB  - Nanoscale therapeutic interventions are increasingly important elements in the
      portfolio of cancer therapeutics. The efficacy of nanotherapeutics is dictated,
      in part, by the access they have to tumors via the leaky tumor vasculature. Yet,
      the extent of tumor vessel leakiness in individual tumors varies widely resulting
      in a correspondingly wide tumor dosing and resulting range of responses to
      therapy. Here we report the design of a multifunctional nanocarrier that
      simultaneously encapsulates a chemotherapeutic and a contrast agent which enables
      a personalized nanotherapeutic approach for breast cancer therapy by permitting
      tracking of the nanocarrier distribution by mammography, a widely used imaging
      modality. Following systemic administration in a rat breast tumor model, imaging
      demonstrated a wide range of intratumoral deposition of the nanocarriers,
      indicating variable tumor vessel leakiness. Notably, specific tumors that
      exhibited high uptake of the nanocarrier as visualized by imaging were precisely
      the animals that responded best to the treatment as quantified by low tumor
      growth and prolonged survival.

PMID- 18814909
TI  - The inhibition of Staphylococcus epidermidis biofilm formation by vancomycin
      modified titanium alloy and implications for the treatment of periprosthetic
      infection.
AB  - Peri-prosthetic infections are notoriously difficult to treat as the biomaterial
      implant is ideal for bacterial adhesion and biofilm formation, resulting in
      decreased antibiotic sensitivity. Previously, we reported that vancomycin
      covalently attached to a Ti alloy surface (Vanc-Ti) could prevent bacterial
      colonization. Herein we examine the effect of this Vanc-Ti surface on
      Staphylococci epidermidis, a Gram-positive organism prevalent in orthopaedic
      infections. By direct colony counting and fluorescent visualization of live
      bacteria, S. epidermidis colonization was significantly inhibited on Vanc-Ti
      implants. In contrast, the gram-negative organism Escherichia coli readily
      colonized the Vanc-Ti rod, suggesting retention of antibiotic specificity. By
      histochemical and SEM analysis, Vanc-Ti prevented S. epidermidis biofilm
      formation, even in the presence of serum. Furthermore, when challenged multiple
      times with S. epidermidis, Vanc-Ti rods resisted bacterial colonization. Finally,
      when S. epidermidis was continuously cultured in the presence of Vanc-Ti, the
      bacteria maintained a Vanc sensitivity equivalent to the parent strain. These
      findings indicate that antibiotic derivatization of implants can result in a
      surface that can resist bacterial colonization. This technology holds great
      promise for the prevention and treatment of periprosthetic infections.

PMID- 18814910
TI  - Ultraviolet light and photosensitising agents activate TRPA1 via generation of
      oxidative stress.
AB  - TRPA1, a Ca(2+)-permeable cation channel that is expressed in sensory neurones,
      is involved in the perception of chemical irritants and mechanical hyperalgesia.
      TRPA1 is activated by either covalent or reversible binding of various chemical
      compounds, including allylisothiocyanate or acrolein, and is further sensitised
      by increases in the intracellular Ca(2+) concentration. We here demonstrate that
      TRPA1 confers a sensitivity towards near ultraviolet (UVA) light, which rapidly
      causes Ca(2+) entry. In electrophysiological recordings in whole cell and inside
      out modes, exposure to UVA light activated typical TRPA1 currents in a wavelength
      dependent and membrane-delimited manner. In the presence of the photosensitising
      agents acridine orange (100 nM) or hypericin (10 nM), the sensitivity of light
      induced TRPA1 activation was increased and extended towards the visible spectrum.
      Since extracellular application of hydrogen peroxide mimicked the effect of UVA
      irradiation and since dithiothreitol partly reversed the activation by UVA
      exposure, we conclude that reactive oxygen species may mediate the light-induced
      activation of TRPA1. Accordingly, hydrogen peroxide induced a TRPA1 activation
      with a membrane-delimited mode of action that was attenuated by dithiothreitol.
      Intracellular but not extracellular application of FeSO(4), which catalyses the
      formation of highly reactive hydroxyl radicals potentiated the hydrogen peroxide
      stimulated TRPA1 activation. We conclude that, via generation of reactive oxygen
      species, light-induced TRPA1 activation provides an additional mode of
      activation, which renders TRPA1 a likely molecular candidate in processes leading
      to painful or burning sensations during photodynamic therapy or upon local
      application of hydrogen peroxide.

PMID- 18814911
TI  - Effect of polymyxin B and environmental conditions on isolation of Brucella
      species and the vaccine strain RB51.
AB  - Brucella are resistant to polymyxin B (PB), but their relative susceptibility to
      PB and its derivative, colistin (COL) has not been rigorously or systematically
      studied. Comparative susceptibility of Brucella reference strains, vaccine strain
      RB51, and Brucella isolates from marine mammals to these two cationic peptides
      were determined by Etest. Vast differences among Brucella species were found in
      susceptibility to both PB and COL. Brucella demonstrated similar pattern of
      relative susceptibility to PB as that of COL, but they were less susceptible to
      COL. Both B. melitensis and B. suis were the least susceptible to polymyxins and
      rough strains were more susceptible to both PB and COL than the smooth except for
      the BvrR mutant. Strains were generally less susceptible to PB when cultured in
      CO(2) rather than ambient air; some became more susceptible in acidified medium.
      Results show that environment cultural conditions must be considered when
      selecting for CO(2)-independent strains of Brucella especially the vaccine strain
      RB51 on selective media containing PB. Our observations extend basic knowledge of
      the differential resistance of Brucella to polymyxins.

PMID- 18814912
TI  - Lessons from a project to create performance measures for public health.
AB  - This paper uses a specific example to illustrate complications that arise in
      formulating and implementing performance measures. The context of this
      demonstration is a Centers for Disease Control and Prevention (CDC)-funded
      project to explore the feasibility of performance measures developed at the
      national level for local sexually transmitted disease (STD) prevention and
      control programs. Grantees provided local data and reported on their experience
      in eliciting the data and using the results for program development. The
      experience of this project suggests that measures can be made operationally
      feasible and programmatically useful only if terminologies are subjected to
      extensive definition and clarification activities. These activities must include
      development of common language, mapping of workflows, and clarification of
      spheres of influence. Finally, performance measures must be used with some
      caution, as they often unintentionally capture extraneous program elements.

PMID- 18814913
TI  - Estimating human exposure to transport noise in central Dublin, Ireland.
AB  - This paper reports on research conducted to determine estimates of the extent of
      environmental noise exposure from road transport on residents and workers in
      central Dublin, Ireland. The Harmonoise calculation method is used to calculate
      noise values for the study area while a Geographical Information System (GIS) is
      utilised as a platform upon which levels of noise exposure are estimated.
      Residential exposure is determined for L(den) and L(night) while worker exposure
      is determined for L(den). In order to analyse the potential of traffic management
      as a noise abatement measure, traffic was redirected from the main residential
      areas to alternative road links and the revised exposure levels were determined.
      The results show that the extent of noise exposure in Dublin is considerable, and
      in relative terms, it is worse for the night-time period. In addition, the
      results suggest also that traffic management measures have the potential to lead
      to significant reductions in the level of noise exposure provided that careful
      consideration is given to the impact of traffic flows on residential populations.

PMID- 18814914
TI  - High prevalence of Neisseria meningitidis hypervirulent lineages and emergence of
      W135:P1.5,2:ST-11 clone in Southern Brazil.
AB  - OBJECTIVES: The aim of this study was to characterize Neisseria meningitidis
      strains causing invasive disease in Rio Grande do Sul (RS), during 2003-2005,
      monitoring the occurrence of hypervirulent lineages, as well as to determine the
      diversity of PorA VR types for the corresponding isolates and clinical specimens.
      METHODS: Isolates and clinical specimens were characterized by MLST and PorA VR
      typing. RESULTS: This study demonstrated high prevalence of some hypervirulent
      lineages and emergence of new ones, including the emergence of lineages
      W135:P1.5,2:ST-11 complex, and C:P1.22,14-6:ST-103 complex. These lineages are
      probably responsible for the increasing incidence of serogroups C and W135,
      despite the overall decrease in serogroup B cases during the period. The most
      prevalent complex was serogroup B ST-32/ET-5 complex. The most prevalent PorA
      types found for serogroup B were P1.19,15, P1.7,16, and P1.18-1,3, representing a
      different distribution of PorA types compared to other states of Brazil.
      CONCLUSIONS: This study highlights the importance of monitoring each population,
      even within the same country. The different distribution of PorA VR types in RS
      has implications in vaccine design and efficacy. Detailed and accurate
      meningococcal characterization is an important element in studies of
      meningococcal epidemiology, population biology, and evolution and provides
      information for the design of control strategies.

PMID- 18814915
TI  - Axis II comorbidity in euthymic bipolar disorder patients: no differences between
      bipolar I and II subtypes.
AB  - BACKGROUND: Bipolar disorder type II (BDII) has been considered since its
      distinction from bipolar disorder type I (BDI) as a milder form, on the basis of
      cross-sectional symptoms intensity. Longitudinal data, on the contrary, do
      suggest that it is at least as severe as BDI, if not even more chronic and
      impairing. Few studies investigated differences in Axis II comorbidity in bipolar
      disorder patients according to bipolar subtypes, and none examined patients
      during prolonged euthymia. The aim of the study was to determine comorbidity
      rates for personality disorders in euthymic bipolar subjects, comparing bipolar
      type I and II disorders (BDI and BDII). METHODS: 186 DSM-IV (SCID-I) bipolar
      disorder subjects were enrolled; all patients were euthymic for at least two
      months, as confirmed by a HAM-D<8 and a YMRS<6. Axis II comorbidity was evaluated
      through SCID-II. Differences in Axis II comorbidity rates were examined with the
      Pearson's Chi-square test. RESULTS: Of the subjects included, 71 had BDI and 115
      BDII. At least a personality disorder was present in 42.5% of all bipolars, 43.7%
      of BDI and 41.7% of BDII. No differences were detected between the two subgroups
      for any single personality disorder. LIMITATIONS: We relied only on the patients'
      reports in assessing personality disorders; the sample was made of subjects
      referred to a tertiary centre who were able to maintain euthymia. CONCLUSIONS:
      Our study confirms the high comorbidity rates for personality disorders in
      bipolar subjects and provides evidence that BDII, with regard to Axis II
      comorbidity, is as severe as BDI.

PMID- 18814916
TI  - Chronic stress and stressful life events in the offspring of parents with bipolar
      disorder.
AB  - BACKGROUND: The stress generation theory suggests that depressed individuals and
      children of depressed mothers are prone to create stressors that are
      interpersonal and dependent on their own behaviour. Exposure to "self-generated"
      stress is believed to increase the risk for onset and recurrence of depression.
      Much less is known about stress in the offspring of parents with bipolar disorder
      (OBD). METHODS: As part of a longitudinal study, 37 OBD and 33 offspring of
      parents with no affective disorder (13 to 26 years old) were interviewed using
      the UCLA Life Stress Interview, assessing their current life circumstances
      (chronic stress) and recent negative life events (episodic stress). RESULTS: The
      OBD reported more difficulties in interpersonal and non-interpersonal domains of
      chronic stress than controls. The group differences remained significant after
      controlling for the presence of affective disorders, indicating that the effect
      of risk status on chronic stress is independent of the problems associated with
      having a disorder. With respect to episodic stress, the OBD were 3.9 times more
      likely to have experienced a moderate to severe interpersonal stressor compared
      to the control group. There was no group difference for dependent events, but the
      OBD experienced more severe independent events than controls. LIMITATIONS:
      Methodological limitations include a small sample size, large age range, and the
      absence of parent-reported stress and symptomatology. CONCLUSIONS: Although the
      findings do not support the stress generation theory, they suggest that elevated
      levels of episodic and chronic stress may be important markers of risk for
      affective disorders in high-risk participants.

PMID- 18814917
TI  - Comparison of clinical and research assessments of diagnosis, suicide attempt
      history and suicidal ideation in major depression.
AB  - A number of studies have compared clinical diagnostic and suicide assessments to
      standardized schedules to determine the level of agreement. At best there is only
      moderate diagnostic agreement, but most often it is fair. There are only a few
      reports comparing clinical assessments for suicidal behavior with standardized
      schedules. We present the data from 201 inpatient admissions for major depression
      that had both clinical diagnostic and suicide evaluations by PGYII resident
      physicians under supervision from an attending psychiatrist and research
      evaluations using standardized schedules for diagnosis and suicide by at least
      masters' level clinicians. There was moderate agreement for diagnosis and suicide
      attempt history but only fair agreement for the presence of suicidal ideation
      using Cohen's kappa statistic. In regards to suicide attempt history a cross
      tabulation demonstrated that 18.7% of those patients identified by a research
      schedule as having a past suicide attempt were not identified as such by the
      clinicians. A cross-tabulation demonstrated that 29.7% of those patients
      identified by structured interview as having suicidal ideation were not
      identified as such by the clinician. There was a statistically significant
      difference in the level of agreement for suicide attempt history between clinical
      and research assessments for attempts within a year of admission and those beyond
      a year. These findings suggest the importance of adding a structured diagnostic
      and suicide assessment to routine clinical care to improve the reliability and
      validity of clinical evaluations and to inform treatment planning to benefit our
      patients.

PMID- 18814918
TI  - Association of leptin with inflammatory cytokines and lymphocyte subpopulations
      in peritoneal fluid of patients with endometriosis.
AB  - INTRODUCTION: Endometriosis is a common, complex and chronic disease related to
      ectopic implantation and growth of endometrial tissue that may manifest by pelvic
      inflammatory reactions, chronic pelvic pain and subfertility. Endometriosis may
      be associated with increased peritoneal fluid leptin levels. Leptin is known to
      exert immunomodulatory effects; however, an association between leptin and
      inflammatory reactions in endometriosis has not been documented. Therefore, the
      aim of this study was to investigate a relationship between leptin concentrations
      in peritoneal fluid and the levels of peritoneal fluid inflammatory cytokines and
      mononuclear leukocyte subpopulations. MATERIALS AND METHODS: Peritoneal fluid was
      aspirated by laparoscopy from 46 women in whom endometriosis had been confirmed
      by clinical and histopathological examinations and from 10 control women
      qualified for ART in whom pelvic pathology has been excluded. Concentrations of
      leptin and inflammatory cytokines (IL-1beta, IL-6, IFN-gamma and TNF) in
      peritoneal fluid were evaluated by specific ELISAs. Percentage of peritoneal
      leukocyte subpopulations (CD3+, CD4+, CD8+ and CD14+) was analyzed by FACS using
      specific monoclonal antibodies. RESULTS: Leptin concentrations in peritoneal
      fluid correlated negatively with concentrations of IL-1beta and IFN-gamma (r(s)=
      0.38, p=0.01 and r(s)=-0.31, p=0.03, respectively) and correlated positively with
      the percentage of CD3+ pan-T cells (r(s)=0.69, p=0.009) and CD4+ T helper cells
      (r(s)=0.74, p=0.036). CONCLUSIONS: Increased leptin levels in peritoneal fluid
      from endometriosis patients may affect local inflammatory/immune reactions,
      especially infiltration of CD4+ T helper cells. Thus, leptin may play an
      important role in the immunopathogenesis of endometriosis.

PMID- 18814919
TI  - Mid-pregnancy circulating cytokine levels, histologic chorioamnionitis and
      spontaneous preterm birth.
AB  - Some spontaneous preterm deliveries (PTD) are caused by occult infections of the
      fetal membranes (histologic chorioamnionitis [HCA]). High levels of infection
      related markers, including some cytokines, sampled from maternal circulation in
      mid-pregnancy have been linked to PTD, but whether these specifically identify
      HCA has not been established. We have tested associations between 13 Th1, Th2 and
      Th17 cytokines and PTD with and without HCA in a prospective cohort study. The
      study sample included 926 Pregnancy Outcomes and Community Health Study subcohort
      women; women with medically indicated PTD or incomplete data excluded. A panel of
      cytokines was assessed using a multiplex assay in maternal plasma collected at 15
      27 weeks of gestation. Severe HCA was scored by a placental pathologist blinded
      to clinical variables. Multivariable polytomous logistic regression was used to
      estimate adjusted odds ratios (OR) per 1 standard deviation (S.D.) increase in
      cytokine levels using a 5 level outcome variable: PTD <35 weeks with HCA, PTD <35
      weeks without HCA, PTD 35-36 weeks with HCA, PTD 35-36 weeks without HCA, and
      term (referent). Interleukin (IL)-1beta, IL-2, IL-12, interferon-gamma, IL-4, IL
      6 and transforming growth factor-beta were all significantly associated with PTD
      <35 weeks with HCA, with ORs of 1.6-2.3 per S.D. increase. None of these were
      associated with PTD <35 weeks without HCA or PTD 35-36 weeks with HCA. Although
      the tissues of origin of circulating cytokines are unclear, the observed
      elevations across many cytokines among women who later delivered <35 weeks with
      HCA may represent a robust immune response to infection within gestational
      tissues. These results suggest that women with HCA could be identified using
      relatively non-invasive means.

PMID- 18814920
TI  - Chronic restraint stress promotes immune suppression through toll-like receptor 4
      mediated phosphoinositide 3-kinase signaling.
AB  - Stress, either psychological or physical, can have a dramatic impact on the
      immune system. Toll-like receptors (TLRs) play a pivotal role in the induction of
      innate and adaptive immune response. We have reported that stress modulates the
      immune response in a TLR4-dependent manner. However, the mechanisms underlying
      TLR4-mediated signaling in stress modulation of immune system have not been
      identified. Here, we demonstrate an essential role for the TLR4-mediated
      phosphoinositide 3-kinase (PI3K)/Akt signaling. PI3K inhibition by inhibitors
      wortmannin or LY294002 abrogated protection of stress-induced immune suppression
      in TLR4-deficient mice compared with TLR4-deficient mice that did not receive the
      inhibitors. The mechanisms by which PI3K are increased in the TLR4-deficient
      lymphocytes may involve increased phosphorylation of Akt as well as increased
      phosphorylation of glycogen synthase kinase-3 beta (GSK-3 beta). The stress
      mediated suppression of T help 1 (Th1) cytokine and increased production of Th2
      cytokine was greatly reduced in TLR4 deficient mice compared with the wild type
      mice. Moreover, inhibition of PI3K diminished protection of the above Th1 and Th2
      changes caused by stress in TLR4-deficient mice compared with non-stressed mice
      and the wild type mice. Our data demonstrated that TLR4 negatively regulates PI3K
      activity in wild type mice, leading to the observed the stress-induced immune
      response. The higher levels of PI3K prevent TLR4 deficient mice from the stress
      induced immune response. Therefore, stress modulates the immune system through
      TLR4-mediated PI3K/Akt signaling.

PMID- 18814921
TI  - Audiologic and vestibular findings in a sample of human immunodeficiency virus
      type-1-infected Mexican children under highly active antiretroviral therapy.
AB  - OBJECTIVE: There is little information about audiologic and vestibular disorders
      in pediatric patients infected with the Human Immunodeficiency Virus type-1 (HIV
      1). The aim of this study was to evaluate audiologic and vestibular disorders in
      a sample of HIV-1-infected children receiving Highly Active Antiretroviral
      Therapy. METHODS: Patients underwent pure tone audiometry, speech discrimination
      testing, auditory brainstem responses, electronystagmography, and rotatory
      testing. HIV-1 viral load and absolute CD4+ cell counts were registered. RESULTS:
      Twenty-three patients were included, aged 4.5 years (median, range 5 months to 16
      years). Pure tone audiometry was carried out in 12 children over 4 years of age:
      4 (33%) showed hearing loss, 2 were conductive. Auditory brainstem responses were
      measured in all 23 patients, suggesting conductive hearing loss in 6 and
      sensorineural hearing loss in 2. Most patients with conductive hearing loss had
      the antecedent of acute or chronic suppurative otitis media but with dry ears at
      the time of evaluation (p=0.003). Abnormal prolongations of interwave intervals
      in auditory brainstem responses were observed in 3 children (13%, 4 ears), an
      abnormal morphology in different components of auditory brainstem responses in 4
      (17.4%, 7 ears), and abnormal amplitude patterns in 11 patients (48%, 17 ears).
      Vestibular tests were abnormal in all six patients tested, with asymmetries in
      caloric and rotatory tests. Although differences were not significant, in
      general, audiologic abnormalities were more frequent in patients with more
      prolonged HIV-1 infections, higher viral loads, or lower absolute CD4+ cell
      counts. CONCLUSIONS: Conductive hearing loss associated with previous otitis
      media events, abnormalities in auditory brainstem responses suggesting disorders
      at different levels of the auditory pathways, and unilateral vestibular
      hyporeflexia were frequent findings in our sample of HIV-1-infected children
      under Highly Active Antiretroviral Therapy. These findings suggest that HIV-1
      infected children should be submitted to audiologic and vestibular evaluation as
      early as possible in order to reduce their impact on the psychosocial development
      of these patients.

PMID- 18814922
TI  - The use of buccal flap in the closure of posterior post-palatoplasty fistula.
AB  - OBJECTIVE: Palatal fistulation is a common complication after cleft palate
      repair, it could occur at any site along the line of cleft closure. Many
      techniques have been proposed for its repair. However, the incidence of
      recurrence after initial fistula closure is high. The aim of this study is to
      evaluate the efficacy of closure of posterior palatal fistula using buccal
      myomucosal flap. METHOD: Fifteen cases with posterior palatal fistulas - after
      cleft palate repair - were included in this study. Their fistulas were closed in
      two-layers; an oral mucoperiosteum hinge flap to reconstruct the nasal side and a
      buccal myomucosal flap from the inner surface of the cheek to reconstruct the
      oral side. Follow-up was carried out for 1 year. RESULTS: The fistulas were
      completely closed in all cases (100%) with no failure or recurrence. This was a
      single-stage operation in all cases, with no need for further procedure to divide
      the pedicle of the flap. CONCLUSIONS: Closure of posterior palatal fistula using
      buccal myomucosal flap in addition to mucoperiosteal flap is a useful method with
      high success rate and no morbidity.

PMID- 18814923
TI  - G(12)/G(13)-mediated signalling in mammalian physiology and disease.
AB  - The human genome encodes hundreds of G-protein-coupled receptors. Their
      intracellular effects, however, are mediated by only four families of
      heterotrimeric G proteins: G(s), G(i)/G(o), G(q)/G(11) and G(12)/G(13). Progress
      in the knowledge about the G(12)/G(13) family has somewhat lagged behind because
      their downstream effectors remained unknown for several years, and tools to
      specifically interfere with G(12)/G(13)-mediated signalling were, therefore,
      missing. However, with the identification of G(12)/G(13)-regulated signalling
      pathways and the recent application of new techniques, such as conditional gene
      inactivation, RNA interference or expression of inhibitory proteins, new insights
      into the in vivo functions of this G-protein family have been gained. It has
      become clear that this pathway regulates cellular proliferation, movement and
      morphology in many different organs and that it is centrally involved in various
      diseases including cancer and cardiovascular disorders. Here, we focus on recent
      progress made in the analyses of the in vivo functions of mammalian G(12)/G(13)
      mediated signalling.

PMID- 18814924
TI  - The health-care in the extreme longevity.
AB  - The increase in life expectancy, the decrease of birth rate, and of the death
      rate in advanced ages caused, particularly in the industrialized countries, a
      progressive demographic transformation of the society, characterized by an
      increased proportion of the elderly. We assist an inevitable increase of
      morbidity and disability, not only due to the global aging of the population, but
      mainly to the increase of the age class above 80 years. For this reason, it is
      necessary to create and/or effort, especially in the Western countries, an
      adequate health-caring network. This should integrate and interact between the
      hospitals and the territories, offering all sanitary services (e.g., assisted
      sanitary residences, day hospitals (DHs), hospices, Alzheimer centers, diurnal
      centers, integrated domiciliary care (IDC), general practitioners), required by
      the elderly, and particularly by the oldest old people. All this should be
      maintained by an adequate financial support of the social-economic sources, which
      are necessary not only to activate the health-care services, but also to favor
      the economic and fiscal stimulation toward the families maintaining the elderly
      patients.

PMID- 18814925
TI  - An alternative exercise and its beneficial effects on glycaemic control and
      oxidative stress in subjects with type 2 diabetes.
AB  - This study investigated the effect of arm swing exercise (ASE) on glycaemic
      control and oxidative stress in type 2 diabetic patients. The results suggest a
      protective effect of the ASE training on vascular complications by improving
      oxidative stress in according to either improved glycaemic control or exercise
      per se.

PMID- 18814926
TI  - Additive effect of diabetes mellitus and hypertension on coronary flow velocity
      reserve and aortic distensibility in patients with negative coronary angiograms.

PMID- 18814927
TI  - Prevalence of diabetes mellitus and other abnormalities of glucose tolerance in
      young adults aged 20-40 years in North India (Kashmir Valley).
AB  - AIMS: To assess the burden of type 2 diabetes mellitus (T2DM) and other
      abnormalities of glucose tolerance in young-adult (20-40 years) men and non
      pregnant women. METHODS: Prevalence of diagnosed T2DM, undiagnosed T2DM and other
      abnormalities of glucose tolerance studied in 3032 subjects from Kashmir Valley
      of India. The study included a questionnaire, anthropological measurements, blood
      sampling, and a standard OGTT. RESULTS: Eight (0.3%) of surveyed subjects were
      previously diagnosed to have diabetes. Of 3024 subjects screened, prevalence of
      diabetes, impaired glucose tolerance (IGT), and impaired fasting glycemia [IFG,
      World Health Organization, Definition, Diagnosis, and Classification of Diabetes
      Mellitus and its Complications. Part 1. Diagnosis and Classification of Diabetes
      Mellitus, World Health Organization, Geneva, 1999], IFG [American Diabetes
      Association, Diagnosis and classification of diabetes mellitus, Diabetes Care 27
      (Suppl. 1) (2004) S5-S10] was 2.5%, 2.0%, 11.9% and 26.7%, respectively. Overall,
      age-adjusted prevalence of T2DM (known plus unknown), IGT, IFG (WHO) and IFG
      (ADA) was 2.4% (95% CI: 1.9-3.0), 1.6% (95% CI: 1.3-2.2), 11.1% (95% CI: 10.0
      12.3), and 25.2% (95% CI: 23.7-26.8), respectively. The difference in diabetes
      prevalence was significant by age, habitat, family history of diabetes and BMI.
      The ratio of known-to-unknown diabetes was 1:10. CONCLUSIONS: This is the first
      large scale study from North India on prevalence of type 2 diabetes in the
      younger age group of 20-40 years. Abnormal glucose tolerance including
      undiagnosed T2DM is common in young adults.

PMID- 18814928
TI  - Incidental reduction in the size of liver hemangioma following use of VEGF
      inhibitor bevacizumab.
AB  - BACKGROUND/AIMS: Hepatic cavernous hemangioma is the second most common liver
      tumor after metastases. Vascular endothelial growth factor (VEGF) is recognized
      as an essential regulator of blood vessel growth. High VEGF expression leads to
      increased angiogenic activity in cavernous hemangioma endothelial cells. The use
      of specific antibodies directed against VEGF abolishes this vascular endothelial
      growth-promoting activity in vitro. Bevacizumab is a recombinant humanized
      monoclonal antibody directed against VEGF which is used for the treatment of
      metastatic colorectal cancer in combination with 5-fluorouracil-based regimens.
      METHODS: We report a patient with invasive colorectal adenocarcinoma and
      suspected liver metastasis on radiological examination, who showed a significant
      decrease in the size of his liver lesions after bevacizumab treatment. Histology
      of the liver lesions revealed hemangioma with a strong staining for VEGF and anti
      VEGFr2 antibody in the hemangioma endothelial cells. To date, surgical resection
      provides the only consistently effective method for treatment of hepatic
      hemangioma. CONCLUSIONS: This is the first documented case of hepatic hemangioma
      responsive to antiangiogenic therapy, suggesting a possible use for these agents
      in treating symptomatic patients without surgery. VEGF-signaling blockade
      including bevacizumab use poses a potential new treatment modality for vascular
      neoplasms in the liver and other sites.

PMID- 18814929
TI  - The undoing of differentiation by four defined factors: A big step forward
      towards generating patient specific pluripotent stem cells.

PMID- 18814930
TI  - Telbivudine: Taking into account baseline and on-therapy predictors.

PMID- 18814931
TI  - Hepatitis C infection and risk of diabetes: a systematic review and meta
      analysis.
AB  - BACKGROUND/AIMS: Several studies found hepatitis C (HCV) increases risk of Type
      II diabetes mellitus (DM). However, others found no or only sub-group specific
      excess risk. We performed meta-analyses to examine whether HCV infection does
      increase DM risk in comparison to the general population and in other sub-groups
      with increased liver disease rates including with hepatitis B (HBV). METHODS: We
      followed standard guidelines for performance of meta-analyses. Two independent
      investigators identified eligible studies through structured keyword searches in
      relevant databases including PubMed. RESULTS: We identified 34 eligible studies.
      Pooled estimators indicated significant DM risk in HCV-infected cases in
      comparison to non-infected controls in both retrospective (OR(adjusted)=1.68, 95%
      CI 1.15-2.20) and prospective studies (HR(adjusted)=1.67, 95% CI 1.28-2.06).
      Excess risk was also observed in comparison to HBV-infected controls
      (OR(adjusted)=1.80, 95% CI 1.20-1.40) with suggestive excess observed in
      HCV+/HIV+ cases in comparison to HIV+ controls (OR(unadjusted)=1.82, 95% CI 1.27
      2.38). CONCLUSIONS: Our finding of excess DM risk with HCV infection in
      comparison to non-infected controls is strengthened by consistency of results
      from both prospective and retrospective studies. The excess risk observed in
      comparison to HBV-infected controls suggests a potential direct viral role in
      promoting DM risk, but this needs to be further examined.

PMID- 18814932
TI  - Chromosomal instability is a risk factor for poor prognosis of adenocarcinoma of
      the lung: Fluorescence in situ hybridization analysis of paraffin-embedded tissue
      from Korean patients.
AB  - BACKGROUND: In this study, we sought to evaluate the prognostic importance of
      chromosomal instability (CIN) in adenocarcinoma (AC) of the lung. The
      relationship between CIN detected by fluorescence in situ hybridization (FISH)
      and survival in AC patients was examined. METHODS: Sixty-three surgical specimens
      of lung AC were analyzed. To identify tumors with CIN, p16 and multi-target DNA
      FISH assays for c-myc, chromosome 6, EGFR, and chromosome 5 (LAVysion, Vysis)
      were performed on nuclei extracted from paraffin-embedded tumor tissues. Survival
      rates were compared in terms of sex, age, histology, T factor, N factor, CIN, and
      smoking status. A sample was classified as CIN-positive if at least three of the
      five chromosomes were positive. RESULTS: Out of the 63 specimens, 32 (39.7%) were
      CIN-positive. The 5-year overall disease-free survival rate was 58.7% as a whole,
      46.9% for CIN-positive patients and 71.0% for the CIN-negative patients [hazard
      ratio (HR), 2.34; 95% confidence interval (CI), 1.04-5.26; p = 0.04]. The 5-year
      overall survival rate was 81.0%, 68.7% for CIN-positive patients and 93.5% for
      the CIN-negative patients (HR, 5.64; 95% CI, 1.23-25.70; p = 0.026). In
      multivariate analysis after adjusting for pathologic nodal staging, tumor
      staging, sex, age, and smoking history, compared with the CIN-negative patients,
      the CIN-positive status remained significantly associated with decreased overall
      survival (HR, 8.48; 95% CI, 1.66-43.42; p = 0.010). CONCLUSIONS: CIN can be
      effectively detected in primary AC of lung using FISH analysis. CIN is associated
      with poor prognosis for AC, and may thus be utilized as an independent prognostic
      factor for the disease.

PMID- 18814933
TI  - Reversing opinions on Dollo's Law.
AB  - Dollo's Law, the idea that the loss of complex features in evolution is
      irreversible, is a popular concept in evolutionary biology. Here we review how
      application of recent phylogenetic methods, genomics and evo-devo approaches is
      changing our view of Dollo's Law and its underlying mechanisms. Phylogenetic
      studies have recently demonstrated cases where seemingly complex features such as
      digits and wings have been reacquired. Meanwhile, large genomics databases and
      evo-devo studies are showing how the underlying developmental pathways and
      genetic architecture can be retained after the loss of a character. With
      dwindling evidence for the law-like nature of Dollo's Law, we anticipate a return
      to Dollo's original focus on irreversibility of all kinds of changes, not
      exclusively losses.

PMID- 18814934
TI  - Implication of phospholipase D in response of Hordeum vulgare root to short-term
      potassium deprivation.
AB  - To verify the possible involvement of lipids and several other compounds
      including hydrogen peroxide (H(2)O(2)) and glyceraldehyde-3-phosphate
      dehydrogenase (G3PDH) in the response of Hordeum vulgare to early potassium
      deprivation, plants were grown in hydroponic conditions for 30d with a modified
      Hewitt nutrient solution containing 3mM K(+). They were then incubated for
      increasing periods of time ranging from 2 to 36h in the same medium deprived of
      K(+). In contrast to leaves, root K(+) concentration showed its greatest decrease
      after 6h of treatment. The main lipids of the control barley roots were
      phospholipids (PL), representing more than 50% of the total lipids. PL did not
      change with treatment, whereas free sterols (FS) decreased following K(+)
      deprivation, showing a reduction of approximately 17% after 36h. With respect to
      the individual PL, 30h K(+) deprivation led to a reduction in phosphatidylcholine
      (PC), phosphatidylserine (PS), and phosphatidylinositol (PI) levels, whereas
      phosphatidylglycerol (PG), phosphatidylethanolamine (PE), and phosphatidic acid
      (PA) levels increased. The maximum PA accumulation and the highest phospholipase
      D (PLD) activation, estimated by an accumulation of phosphatidylbutanol (PtBut),
      were observed after 24h of K(+) starvation. At the root level, H(2)O(2) showed
      the maximum value after 6h of incubation in -K solution. In parallel, G3PDH
      activity reached its minimum. On the basis of a concomitant stimulation of PLD
      activity and, consequently, PA accumulation, enhancement of H(2)O(2) production,
      and inhibition of G3PDH activity, we suggest a possible involvement of these
      three compounds in an early response to K(+) deprivation.

PMID- 18814935
TI  - A randomized trial of diphenhydramine as prophylaxis against metoclopramide
      induced akathisia in nauseated emergency department patients.
AB  - STUDY OBJECTIVE: Akathisia, an adverse effect observed at times after
      administration of parenteral metoclopramide, is an unpleasant symptom complex
      characterized by restlessness and agitation. Some try to limit the development of
      akathisia by coadministering diphenhydramine when using parenteral
      metoclopramide. The goal of this investigation is to determine whether
      concomitant administration of diphenhydramine 25 mg decreased the rate of
      development of akathisia after administration of 10 mg or 20 mg of intravenous
      metoclopramide. METHODS: This was a randomized, double-blind, factorial design
      trial. Patients who presented to our emergency department with a primary or
      secondary chief complaint of nausea were randomized to one of the following 4
      groups: (1) metoclopramide 10 mg+diphenhydramine 25 mg; (2) metoclopramide 10
      mg+placebo; (3) metoclopramide 20 mg+diphenhydramine 25 mg; (4) metoclopramide 20
      mg+placebo. The medications were inserted into a 50-mL bag of normal saline
      solution and administered as an intravenous drip during 15 minutes. Primary
      outcome was development of akathisia within 60 minutes of medication
      administration, as measured by blinded assessors using a short akathisia
      instrument, or use of rescue medication for treatment of akathisia by blinded
      clinical staff. Patients were also asked at baseline and 30 minutes later whether
      they felt restless. RESULTS: Two hundred eighty-nine patients were randomized and
      286 patients were included in the final analysis. Within 1 hour of medication
      administration, 17 of 143 patients randomized to diphenhydramine (12%; 95%
      confidence interval [CI] 8% to 18%) and 17 of 143 (12%; 95% CI 8% to 18%)
      randomized to placebo developed akathisia (95% CI for difference of 0%: -8% to
      8%). Thirteen of 143 patients randomized to metoclopramide 10 mg (9%; 95% CI 5%
      to 15%) and 21 of 143 randomized to metoclopramide 20 mg (15%; 95% CI 10% to 22%)
      developed akathisia (95% CI for difference of 6%: -2% to 14%). In those
      administered prophylactic diphenhydramine, odds of akathisia relative to placebo
      were 1.0 (95% CI 0.5 to 2.0). Odds of akathisia in those administered 20 mg of
      metoclopramide relative to the 10-mg dose were 1.7 (95% CI 0.8 to 3.6). Among
      patients who received 20 mg of metoclopramide, subjective restlessness was
      reported by 7 of 72 (9.7%) patients who received diphenhydramine and 14 of 71
      (19.7%) patients who received placebo (95% CI for difference of 10%: -2% to 22%).
      CONCLUSION: Routine prophylaxis with diphenhydramine to prevent akathisia is
      unwarranted when intravenous metoclopramide is administered over 15 minutes. For
      patients administered 20 mg of metoclopramide, prophylactic diphenhydramine may
      decrease subjective restlessness.

PMID- 18814936
TI  - Letters, libel, and the law.
AB  - Authors of scientific articles and journal editors are subject to antidefamation
      publication laws. We describe our experience with an accusation of libel. We
      define libel as it involves the medical literature and explain the ways in which
      threats of libel influence editorial decisionmaking and lead to negative
      publication bias by presenting examples drawn from the medical and legal
      literature.

PMID- 18814938
TI  - [A pigmented erythema of the thighs].

PMID- 18814937
TI  - Subregional hippocampal atrophy predicts Alzheimer's dementia in the cognitively
      normal.
AB  - Atrophic changes of the hippocampus are typically regarded as an early sign of
      Alzheimer's dementia (AD). Using the radial distance atrophy mapping approach, we
      compared the longitudinal MRI data of 10 cognitively normal elderly subjects who
      remained normal at 3-year and 6-year follow-up (NL-NL) and 7 cognitively normal
      elderly subjects who were diagnosed with mild cognitive impairment (MCI) 2.8
      (range 2.0-3.9) and with AD 6.8 years (range 6.1-8.2) after baseline (NL
      MCI(AD)). 3D statistical maps revealed greater hippocampal atrophy in the NL
      MCI(AD) relative to the NL-NL group at baseline (left p=0.05; right p=0.06)
      corresponding to 10-15% CA1, and 10-25% subicular atrophy, and bilateral
      differences at 3-year follow-up (left p=0.001, right p<0.02) corresponding to 10
      30% subicular, 10-20% CA1, and 10-20% newly developed CA2-3 atrophy. This
      preliminary study suggests that excess CA1 and subicular atrophy is present in
      cognitively normal individuals predestined to decline to amnestic MCI, while
      progressive involvement of the CA1 and subiculum, and atrophy spreading to the
      CA2-3 subfield in amnestic MCI, suggests future diagnosis of AD.

PMID- 18814939
TI  - [Potentially inappropriate medications in the elderly: a list adapted to French
      medical practice].
AB  - Drug induced adverse effects are frequently encountered in geriatrics. Their
      occurrence can be limited by an adapted prescription. Potentially inappropriate
      medications are drugs with an unfavourable benefit to risk ratio when other safer
      or more efficient therapeutic alternatives are available. An expert consensus
      allowed us to establish a new list of potentially inappropriate medications for
      people aged 75 or over, taking into account French prescribing habits. The drugs
      or the drug-classes proposed in this list are, generally speaking, and when
      possible, to be avoided in the elderly, but can be prescribed at times, under
      special clinical conditions, provided that the benefit to risk ratio is assessed.
      The French list proposed here could be considered as (i) an epidemiological tool
      for evaluating the quality of drug prescription in geriatrics and as (ii) a
      prescription guide suggesting an alternative treatment whenever a therapeutic
      alarm is raised. This guide could be used both as a base for the education of
      prescribers and as a way of increasing patients awareness. This French list
      should be kept up-to-date so as to remain adapted to the evolution of the
      knowledge on the effect of drugs in the elderly and of the pharmaceutical market.

PMID- 18814940
TI  - [Resistance to curative treatment by unfractionned heparin].
AB  - Unfractionated heparin has been used as antithrombotic therapy for many years.
      Its main effect is attributed to the activation of antithrombin (AT), the
      heparin/AT complex inactivating both factor IIa (thrombin) and factor Xa.
      Resistance to unfractionated heparin with clinical or biological expression is
      uncommon. The occurrence of venous or arterial thrombosis or the extension of
      thrombosis in a patient receiving unfractionated heparin, should always raise
      suspicion of either AT deficiency or type 2 heparin-induced thrombocytopenia (HIT
      type 2). HIT type 2 is not a true heparin resistance but an immune complication
      that requires heparin discontinuation and the use of alternative anticoagulants.
      Biological heparin resistance is suspected in the presence of a normal or not
      prolonged activated partial thromboplastin time despite the administration of
      increasing dose of heparin. Measurement of anti-Xa activity is useful to adjust
      heparin treatment. Isolated biological heparin resistance is encountered in
      several physiological and pathological situations including inflammatory and
      infectious disorders, pregnancy and thrombocytosis. It also occurs in acquired
      antithrombin deficiency of nephrotic syndrome, l-asparaginase treatment or
      cardiopulmonary bypass. Biological heparin resistance is relatively common, but
      clinically significant resistance to heparin is rare and should always raise
      suspicion of either AT deficiency or type 2 heparin-induced thrombocytopenia.

PMID- 18814941
TI  - [Monoclonal gammopathy and primary colonic mantle cell lymphoma].
AB  - The association of a monoclonal gammopathy (MG) with a B cell non-Hodgkin's
      lymphoma (NHL) is a well-known phenomenon. It has been recognized in many
      subtypes of primary gastrointestinal lymphoma but its association with primary
      colonic mantle cell lymphoma has never been yet described. We report a 65-year
      old man who presented with an exudative ascites and constipation. Serum
      electrophoresis showed a monoclonal peak in the gamma region of 45g/L and
      immunoelectrophoresis confirmed the presence of monoclonal gammopathy of IgM
      kappa type. Bone marrow aspirate was normal. Radiologic and endoscopic
      investigations evidenced a primary colonic mantle cell lymphoma. Although the
      association of an MG with an NHL and, in particular, to a primitive digestive
      location appears a rare phenomenon, endoscopic investigations in patients with MG
      appears legitimate in the presence of any digestive sign.

PMID- 18814942
TI  - Nursing students' level of autonomy: a study from Turkey.
AB  - Nursing curriculum programs developed to train future professional nurses,
      methods of teaching and learning and practice can either prepare or be an
      obstacle to the students' thinking and acting like independent professionals.
      This study was conducted for the purpose of determining the level of autonomy of
      nursing students in the baccalaureate degree program at Cumhuriyet University
      School of Nursing. The research was conducted with a total of 326 students. Two
      forms were used for data collection in the research. The first was a 15-question
      personal information form. The second was the 30 item autonomy subscale from the
      Sociotropy/Autonomy Scale (SAS). The research data were entered into the
      Statistical Package for Social Sciences (SPSS) version 11.0 and frequency
      distribution, arithmetic mean, variance analysis (One-Way ANOVA) and Independent
      Samples t-test were used in the analysis of data. According to the General
      Autonomy (GA) score mean from the SAS administered in this study the nursing
      students' GA score mean was 83.03+/-14.51 and the highest level of autonomy was
      found to be in the 1st year students (84.87+/-14.44), followed consecutively by
      2nd year (83.18+/-15.09), 3rd year (82.72+/-15.80) and 4th year (81.47+/-12.81)
      students. The conclusion of the study is that the autonomy levels of the students
      who regarded the professional qualities given them by the nursing education as
      enough have been remarkably high. This suggests that the nursing curriculum
      program being used is not adequately supporting the development of autonomy in
      students.

PMID- 18814943
TI  - Natural radionuclide content in building materials and gamma dose rate in
      dwellings in Cuba.
AB  - An extensive research project to investigate the radioactive properties of Cuban
      building materials was carried out because there is a lack of information on the
      radioactivity of such materials in Cuba. In the framework of this project 44
      samples of commonly used raw materials and building products were collected in
      five Cuban provinces. The activity concentrations of natural radionuclides were
      determined by gamma ray spectrometry using a p-type coaxial high purity germanium
      detector and their mean values were in the ranges: 9-857Bqkg(-1) for (40)K; 6
      57Bqkg(-1) for (226)Ra; and 1.2-22Bqkg(-1) for (232)Th. The radium equivalent
      activity in the 44 samples varied from 4Bqkg(-1) (wood) to 272Bqkg(-1) (brick). A
      high pressure ionisation chamber was used to measure the indoor absorbed dose
      rate in 543 dwellings and workplaces in five Cuban provinces. The average
      absorbed dose rates in air ranged from 43nGyh(-1) (Holguin) to 73nGyh(-1)
      (Camaguey) and the corresponding population-weighted annual effective dose due to
      external gamma radiation was estimated to be 145+/-40microSv. This value is 51%
      lower than the effective dose due to internal exposure from inhalation of decay
      products of (222)Rn and (220)Rn and it is 16% higher than the calculated value
      for the typical room geometry of a Cuban house.

PMID- 18814944
TI  - Oral mucosal irritation with incorrect use of alendronate.

PMID- 18814945
TI  - Active moss biomonitoring of trace elements with Sphagnum girgensohnii moss bags
      in relation to atmospheric bulk deposition in Belgrade, Serbia.
AB  - Active biomonitoring with wet and dry moss bags was used to examine trace element
      atmospheric deposition in the urban area of Belgrade. The element accumulation
      capability of Sphagnum girgensohnii Russow was tested in relation to atmospheric
      bulk deposition. Moss bags were mounted for five 3-month periods (July 2005
      October 2006) at three representative urban sites. For the same period monthly
      bulk atmospheric deposition samples were collected. The concentrations of Al, V,
      Cr, Mn, Fe, Ni, Cu, Zn, As, Cd, and Pb were determined by instrumental neutron
      activation analyses and atomic absorption spectrometry. Significant accumulation
      of most elements occurred in the exposed moss bags compared with the initial moss
      content. High correlations between the elements in moss and bulk deposits were
      found for V, Cu, As, and Ni. The enrichment factors of the elements for both
      types of monitor followed the same pattern at the corresponding sites.

PMID- 18814946
TI  - Resolution of the EcoRII restriction endonuclease-DNA complex structure in
      solution using fluorescence spectroscopy.
AB  - The X-ray structure for the type IIE EcoRII restriction endonuclease has been
      resolved [X.E. Zhou, Y. Wang, M. Reuter, M. Mucke, D.H. Kruger, E.J. Meehan and
      L. Chen. Crystal structure of type IIE restriction endonuclease EcoRII reveals an
      autoinhibition mechanism by a novel effector-binding fold. J. Mol. Biol. 335
      (2004) 307-319.], but the structure of the R.EcoRII-DNA complex is still unknown.
      The aim of this article was to examine the structure of the pre-reactive R.EcoRII
      DNA complex in solution by fluorescence spectroscopy. The structure for the
      R.EcoRII-DNA complex was resolved by determining the fluorescence resonance
      energy transfer (FRET) between two fluorescent dyes, covalently attached near the
      EcoRII recognition sites, that were located at opposite ends of a lengthy two
      site DNA molecule. Analysis of the FRET data from the two-site DNA revealed a
      likely model for the arrangement of the two EcoRII recognition sites relative to
      each other in the R.EcoRII-DNA complex in the presence of Ca(2+) ions. According
      to this model, the R.EcoRII binds the two-site DNA and forms a DNA loop in which
      the EcoRII recognition sites are 20+/-10 A distant to each other and situated at
      an angle of 70+/-10 degrees.

PMID- 18814947
TI  - Classification of proteins based on similarity of two-dimensional protein maps.
AB  - Data reduction techniques are now a vital part of numerical analysis and
      principal component analysis is often used to identify important molecular
      features from a set of descriptors. We now take a different approach and apply
      data reduction techniques directly to protein structure. With this we can reduce
      the three-dimensional structural data into two-dimensions while preserving the
      correct relationships. With two-dimensional representations, structural
      comparisons between proteins are accelerated significantly. This means that
      protein-protein similarity comparisons are now feasible on a large scale. We show
      how the approach can help to predict the function of kinase structures according
      to the Hanks' classification based on their structural similarity to different
      kinase classes.

PMID- 18814948
TI  - Sequence and stability of the goat cytochrome c.
AB  - We have determined the sequence of mitochondrial cytochrome c (cyt-c) from the
      goat heart, and it was found to have a unique amino acid sequence among all amino
      acid sequences of cyt-c reported till date. Its sequence alignment with the
      bovine cytochrome c (b-cyt-c) led us to conclude that the goat cytochrome c (g
      cyt-c) differs in amino acid sequence from b-cyt-c at only one position, i.e.,
      Pro44(bovine) --> Ala44(goat). It has been observed that guanidinium chloride
      (GdmCl) induces a two-state transition between the native (N) and denatured (D)
      states of g-cyt-c. This conclusion is reached from the coincidence of GdmCl
      induced transition curves monitored by measurements of absorbance at 405, 530 and
      695 nm and circular dichroism (CD) at 222, 416 and 405 nm. Analysis of
      denaturation curves for the Gibbs energy of stabilization suggests that the
      stability of g-cyt-c is, within experimental errors, identical to that of b-cyt
      c. We have also measured the effect of temperature on the equilibrium, N state <-
      > D state of g-cyt-c in the presence of different GdmCl concentrations. These
      measurements gave values of transition temperature (T(m)), changes in enthalpy
      (DeltaH(m)) and heat capacity (DeltaC(p)) of g-cyt-c in the absence of GdmCl,
      which are compared with those of b-cyt-c. We have used crystal structure
      coordinates of b-cyt-c to predict the structure and stability of g-cyt-c, which
      are compared with those of the bovine protein.

PMID- 18814949
TI  - Estimation of the overall kinetic parameters of enzyme inactivation using an
      isoconversional method.
AB  - An isoconversional method is proposed in order to calculate the kinetic
      parameters of enzyme inactivation. The method provides an efficient and low-cost
      procedure to describe both operational and thermal inactivation. Unlike the
      ordinary kinetic assays performed at constant enzyme concentration and at various
      substrate concentrations, the isoconversional method requires several extended
      kinetic curves for constant initial substrate concentration and different enzyme
      concentrations. The procedure was tested and validated using simulated data
      obtained for several kinetic models frequently discussed in the literature. After
      the validation, the isoconversional method was used for the investigation of the
      thermoinactivation of urease during urea hydrolysis in self buffered medium and
      the operational inactivation (destructive oxidation by excess peroxide) of
      catalase at high concentration of hydrogen peroxide. The results showed that the
      isoconversional method gives good results of global inactivation constant for
      both simple and more complex models.

PMID- 18814950
TI  - Thrombopoietin regulates c-Myb expression by modulating micro RNA 150 expression.
AB  - OBJECTIVE: Mice harboring c-Myb hypomorphic mutations display enhanced
      thrombopoiesis because of increased numbers of megakaryocytes and their
      progenitors. Thrombopoietin induces these same effects, which lead us to
      hypothesize that the hormone acts through modulation of c-Myb expression, as c
      Myb levels falls during thrombopoietin-induced megakaryocyte (MK) maturation.
      Micro RNAs (miRs) downregulate gene expression by binding to the 3' untranslated
      region (UTR) of specific messenger RNAs (mRNAs); we noted that the 3'UTR of c-Myb
      contains four miR-150 binding sites. MATERIALS AND METHODS: We used quantitative
      reverse transcriptase polymerase chain reaction, Western blotting, and reporter
      gene analyses to assess the response of c-Myb to thrombopoietin stimulation and
      to gain of and loss of miR-150 expression. RESULTS: We found that thrombopoietin
      reduced c-Myb mRNA and protein levels within 7 hours in megakaryocytes and
      UT7/thrombopoietin (TPO) cells. Using a reporter gene containing the c-Myb 3'UTR
      region, including its four miR150 binding sites, we found that expression of
      miR150 reduced luciferase expression to 50% of baseline at 24 hours and to 25% at
      48 hours in UT7/TPO cells. Quantitative polymerase chain reaction and Western
      blotting also revealed that miR-150 reduced endogenous c-Myb mRNA and protein to
      50% in UT7/TPO cells, and to 65% in mature megakaryocytes. Converse experiments
      utilizing anti-miR150 increased luciferase activity twofold over control anti
      miR. Finally, TPO increased miR150 expression 1.8-fold within 24 hours and 3.4
      fold within 48 hours. CONCLUSIONS: These findings establish that miR150
      downmodulates c-Myb levels, and because TPO affects miR150 expression, our
      results indicate that, in addition to affecting MK progenitor cell growth, TPO
      downmodulates c-Myb expression through induction of miR-150.

PMID- 18814951
TI  - Gene-expression profiles of peripheral blood mononuclear cell subpopulations in
      acute graft-vs-host disease following cord blood transplantation.
AB  - OBJECTIVE: Compared with allogeneic hematopoietic stem cell transplantation using
      other sources, cord blood (CB) transplantation (CBT) has clinical advantages in
      terms of incidence and severity of acute graft-vs-host disease (GVHD), despite
      using allogeneic stem cells with more human leukocyte antigen mismatches.
      However, detailed pathophysiology of acute GVHD developed after CBT has not yet
      been elucidated. In this study, we aimed to clarify the molecular mechanism of
      acute GVHD after CBT. MATERIALS AND METHODS: We performed microarray expression
      profiling of immunoregulatory genes on each of four subpopulations (CD4+, CD8+,
      CD14+, and CD56+) of peripheral blood mononuclear cells (PBMCs), which were taken
      from eight patients with hematologic malignancies who suffered from acute GVHD
      after unrelated CBT. RESULTS: We identified 55 genes, which were differentially
      expressed during acute GVHD compared to recovery phase. Among them, 22 showed
      differential expression concurrently in multiple PBMC subpopulations. In
      particular, five genes (TNFSF10/TRAIL, IL1RN, IFI27, GZMB, and CCR5) were
      upregulated and three genes (CLK1, TNFAIP3 and BTG1) were downregulated in at
      least three out of four subpopulations during acute GVHD. In addition,
      downregulation of antiinflammatory factors, such as TNFAIP3, KLF2, ZFP36, and
      BTG1, seems to be involved in acceleration of immune response, thus exacerbation
      of acute GVHD. Meanwhile, differential expression of several genes, such as CCL5,
      TNFAIP3, KLRB1/CD161, BY55/CD160, and PTGS2/COX2, was assumedly affected by the
      developmental immaturity of CB-derived cells. CONCLUSIONS: These results will
      contribute to the understanding of molecular mechanism underlying the behavior of
      inflammatory cells during acute GVHD following CBT.

PMID- 18814952
TI  - Effect of impeller type and mechanical agitation on the mass transfer and power
      consumption aspects of ASBR operation treating synthetic wastewater.
AB  - The effect of flow type and rotor speed was investigated in a round-bottom
      reactor with 5 L useful volume containing 2.0 L of granular biomass. The reactor
      treated 2.0 L of synthetic wastewater with a concentration of 800 mgCOD/L in 8-h
      cycles at 30 degrees C. Five impellers, commonly used in biological processes,
      have been employed to this end, namely: a turbine and a paddle impeller with six
      vertical-flat-blades, a turbine and a paddle impeller with six-45 degrees 
      inclined-flat-blades and a three-blade-helix impeller. Results showed that
      altering impeller type and rotor speed did not significantly affect system
      stability and performance. Average organic matter removal efficiency was about
      84% for filtered samples, total volatile acids concentration was below 20 mgHAc/L
      and bicarbonate alkalinity a little less than 400 mgCaCO3/L for most of the
      investigated conditions. However, analysis of the first-order kinetic model
      constants showed that alteration in rotor speed resulted in an increase in the
      values of the kinetic constants (for instance, from 0.57 h(-1) at 50 rpm to 0.84
      h(-1) at 75 rpm when the paddle impeller with six-45 degrees -inclined-flat
      blades was used) and that axial flow in mechanically stirred reactors is
      preferable over radial-flow when the vertical-flat-blade impeller is compared to
      the inclined-flat-blade impeller (for instance at 75 rpm, from 0.52 h(-1) with
      the six-flat-blade-paddle impeller to 0.84 h(-1) with the six-45 degrees 
      inclined-flat-blade-paddle impeller), demonstrating that there is a rotor speed
      and an impeller type that maximize solid-liquid mass transfer in the reaction
      medium. Furthermore, power consumption studies in this reduced reactor volume
      showed that no high power transfer is required to improve mass transfer (less
      than 0.6 kW/10(3)m3).

PMID- 18814953
TI  - Influence of support material on the immobilization of biomass for the
      degradation of linear alkylbenzene sulfonate in anaerobic reactors.
AB  - Two horizontal-flow anaerobic immobilized biomass reactors (HAIB) were used to
      study the degradation of the LAS surfactant: one filled with charcoal (HAIB1) and
      the other with a mixed bed of expanded clay and polyurethane foam (HAIB2). The
      reactors were fed with synthetic substrate supplemented with 14 mg l(-1)of LAS,
      kept at 30+/-2 degrees C and operated with a hydraulic retention time (HRT) of
      12h. The surfactant was quantified by HPLC. Spatial variation analyses were done
      to quantify organic matter and LAS consumption along the reactor length. The
      presence of the surfactant in the load did not affect the removal of organic
      matter (COD), which was close to 90% in both reactors for an influent COD of 550
      mg l(-1). The results of a mass balance indicated that 28% of all LAS added to
      HAIB1 was removed by degradation. HAIB2 presented 27% degradation. Molecular
      biology techniques revealed microorganisms belonging the uncultured Holophaga
      sp., uncultured delta Proteobacterium, uncultured Verrucomicrobium sp.,
      Bacteroides sp. and uncultured gamma Proteobacterium sp. The reactor with biomass
      immobilized on charcoal presented lower adsorption and a higher kinetic
      degradation coefficient. So, it was the most suitable support for LAS anaerobic
      treatment.

PMID- 18814954
TI  - Sustainability, substance-flow management, and time, Part II: Temporal impact
      assessment (TIA) for substance-flow management.
AB  - High-quality food and general good health are fundamental needs that have to be
      satisfied if society is to attain a high standard of living. Accordingly, a great
      deal of effort is expended in order to guarantee a high quality of food and
      ensure healthy living conditions. Among other things, these efforts entail
      massive substance flows. Significant substance flows are connected with the
      production and consumption of food and can be regarded from an economic, social,
      or environmental point of view. Substance flows are a part of both nature and the
      anthroposphere. This study demonstrates that food production at present is not
      linked to societal issues of production and sustainability; rather, it shows that
      a systematic approach and an analysis of issues and measures to be taken are
      required. This interconnectedness can be described as a timescape, in analogy to
      a landscape. For proper orientation in a landscape, a map is helpful, especially
      in combination with a compass. In the same way, we need a temporal orientation.
      Time scales serve as a compass to give orientation. A complete temporal analysis
      that includes all relevant temporalities provides the information that is encoded
      in a map. What has to be learned and exercised is the reading of such temporal
      maps. One method of doing this is temporal impact analysis (TIA). Temporal impact
      analysis brings issues that are not normally focused on into the foreground. It
      allows a better understanding of the implications of certain substance flows and
      the measures necessary for their management, and it provides an opportunity to
      develop a more sustainable management of substance flows.

PMID- 18814955
TI  - Six-year follow-up of botulinum toxin A intradetrusorial injections in patients
      with refractory neurogenic detrusor overactivity: clinical and urodynamic
      results.
AB  - BACKGROUND: Most reports in the literature on botulinum toxin A (BoNTA) therapy
      for neurogenic detrusor overactivity (NDO) are based on the results of a single
      injection. Because most patients may require retreatment, the efficacy and safety
      of multiple injections must be addressed clearly. OBJECTIVE: To investigate the
      effectiveness and safety of BoNTA intradetrusorial injections in a group of
      spinal cord-injured (SCI) patients with refractory detrusor overactivity (DO).
      DESIGN, SETTING, AND PARTICIPANTS: Seventeen SCI patients were prospectively
      included in the study and followed up to 6 yr. INTERVENTION: All patients
      received repeat intradetrusorial injections of BoNTA 300 units (Botox, Allergan,
      Irvine, CA) under cystoscopic control on an inpatient basis. MEASUREMENTS: The
      preliminary assessment included voiding diary, urodynamics, kidney and bladder
      ultrasound, and cystourethrography. Patients also completed a standardised
      quality-of-life (QoL) questionnaire. Clinical evaluation, urodynamics, urinary
      tract imaging, and QoL assessment were repeated every year throughout the follow
      up. RESULTS AND LIMITATIONS: Before treatment, all patients complained of urinary
      incontinence and had DO. Bilateral and monolateral renal pelvis dilatation were
      detected in six and five patients, respectively, and a monolateral and third
      grade vesicoureteral reflux was observed in three. At 6-yr follow-up, a
      significant decrease in the frequency of daily incontinence episodes (p<0.01), a
      significant increase in first uninhibited detrusor contraction and in maximum
      bladder capacity (p<0.001 for both), and a significant decrease in maximum
      pressure of these contractions (p<0.01) were observed. Fifteen patients (88.2%)
      were completely continent. Renal pelvis dilatation and vesicoureteral reflux
      resolved in all cases, and the QoL index significantly increased. Limitations of
      the study are related to the small number of included patients. CONCLUSIONS: In
      SCI patients with refractory NDO who do not want or are unfit for invasive
      reconstructive surgery, BoNTA intravesical treatment represents a valid
      alternative to control DO and urinary incontinence and to preserve upper urinary
      tract function over a long-term follow-up.

PMID- 18814956
TI  - Editorial comment on: Six-year follow-up of botulinum toxin A intradetrusorial
      injections in patients with refractory neurogenic detrusor overactivity: clinical
      and urodynamic results.

PMID- 18814957
TI  - Medical students' exposure to urology in European medical schools: historical
      review and current proposals.

PMID- 18814958
TI  - Editorial comment on: Six-year follow-up of botulinum toxin A intradetrusorial
      injections in patients with refractory neurogenic detrusor overactivity: clinical
      and urodynamic results.

PMID- 18814959
TI  - Identification of novel p53 target genes by cDNA AFLP in glioblastoma cells.
AB  - The p53 plays critical role in cellular functions such as cell cycle arrest and
      apoptosis. We overexpressed wild-type p53 (wt-p53) in U87 glioblastoma cells via
      recombinant adenovirus Ad-GFP-P53 which encodes p53 and green fluorescent
      protein. The transcript profiles were investigated using cDNA amplified fragment
      length polymorphism approach. Semi-quantitative RT-PCR and DNA sequencing results
      for the selected genes showed that Cathepsin B and cell cycle associated protein
      1 or Caprin-I, genes were suppressed whereas Annexin-II gene overexpressed in
      response to the overexpression of wt-p53 gene. Our results suggest that these
      genes could be important mediators of p53-dependent tumor growth suppression in
      glioblastoma.

PMID- 18814960
TI  - Aluminum drinking water treatment residuals (Al-WTRs) as sorbent for mercury:
      Implications for soil remediation.
AB  - The potential of readily available and non-hazardous waste material, aluminum
      drinking water treatment residuals (Al-WTRs), to efficiently sorb and immobilize
      mercury (Hg) from aqueous solutions was evaluated. Al-WTR samples with average
      specific surface area of 48m(2)/g and internal micropore surface area of
      120m(2)/g were used in a series of batch sorption experiments. Obtained sorption
      isotherms indicated a strong affinity of Hg for Al-WTRs. Using the Langmuir
      adsorption model, a relatively high maximum sorption capacity of 79mg Hg/g Al
      WTRs was determined. Sorption kinetic data was best fit to a pseudo-first-order
      model, while the use of the Weber-Morris and Bangham models suggested that the
      intraparticle diffusion could be the rate-limiting step. Also, Al-WTRs
      effectively immoblized Hg in the pH range of 3-8. The results from these short
      term experiments demonstrate that Al-WTRs can be effectively used to remove Hg
      from aqueous solutions. This ability points to the potential of Al-WTRs as a
      sorbent in soil remediation techniques based on Hg-immobilization.

PMID- 18814961
TI  - Metabolic disorders of acute exposure to malathion in adult Wistar rats.
AB  - Malathion is a widely organphosphorus insecticide used in agriculture, which
      shows strong insecticidal effects. However, the use of this insecticide leads to
      disruption in metabolic pathways. The aim of this study is to evaluate the acute
      effects of malathion on metabolic parameters in Wistar rats. Malathion was
      administered orally to rats at a dose of 400mg/kg body weight dissolved in corn
      oil. Glucidic and lipidic status were analyzed in plasma, cholinesterase
      activities were also determined. Malathion induces a transitory hyperglycaemia
      which correlated with depletion on glycogen content. Plasma triglycerides and LDL
      level increased significantly in malathion treated-rats. HDL rate was unchanged
      and cholesterol plasma content decrease transitory but rapidly reached a normal
      level. Results of this study indicate, clearly, that malathion in acute exposure
      leads to a disruption of lipid metabolism with an enhancement in LDL and
      triglyceride contents and may play an important role in the development of
      atherosclerosis and cardiovascular disease. Disruption in plasma lipid profile
      may leads to a kind of insulin resistance which results in hyperglycaemia.

PMID- 18814962
TI  - Toxicity assessment of soil amended with tannery sludge, trivalent chromium and
      hexavalent chromium, using wheat, oat and sorghum plants.
AB  - This work assessed the effect of soil amended with tannery sludge (0, 500, 1000,
      2000, 4000 and 8000 mg Cr kg(-1)soil), Cr(3+) as CrCl(3).6H(2)O (0, 100, 250,
      500, 1000 and 2000 mg Cr kg(-1)soil), and Cr(6+) as K(2)Cr(2)O(7) (0, 25, 50,
      100, 200 and 500 mg Cr kg(-1)soil) on wheat, oat and sorghum plants. Seed
      germination, seedling growth (root and shoot) and Cr accumulation in dry tissue
      were measured. Toxicological parameters; medium effective concentration, no
      observed adverse effect concentration and low observed adverse effect
      concentration were determined. Root growth was the most sensitive assessment of
      Cr toxicity (P<0.05). There was a significant correlation (P<0.0001) between Cr
      accumulation in dry tissue and toxic effects on seedling growth. The three Cr
      sources had different accumulation and mobility patterns; tannery sludge was less
      toxic for all three plant species, followed by CrCl(3).6H(2)O and K(2)Cr(2)O(7).

PMID- 18814963
TI  - Valorization of stabilized river sediments in fired clay bricks: factory scale
      experiment.
AB  - The objective of this study is to demonstrate the practical use of polluted river
      sediments after treatment into brick production. Consequently, a full-scale
      industrial experiment was conducted at a brick factory in the north of France.
      Polluted sediment was stabilized by the Novosol process and then was introduced
      in the mix-design with a substitution ratio of 15% as a partial replacement of
      quartz sand. Approximately 15,000 perforated sediment-amended bricks were
      produced. The produced bricks were then subjected to several qualification tests
      (compressive strength, freeze and thaw resistance, water absorption). The results
      obtained showed that the substitution of quartz sand by treated sediment resulted
      in a significant increase in brick compressive strength and firing shrinkage, and
      in a decrease in porosity and water absorption. Moreover, leaching tests
      performed according to different standards on substituted brick samples showed
      that the quantities of heavy metals leached from crushed bricks were within the
      regulatory limits. Thus substituted bricks can be regarded as non-hazardous
      material.

PMID- 18814964
TI  - An environmentally friendly process; adsorption of radionuclide Tl-201 on fibrous
      waste tea.
AB  - This work presents an investigation of the adsorption of the radionuclide of Tl
      201 from waste water on the fibrous tea factory waste. The experimental
      parameters were chosen as temperature, pH, stirring speed, adsorbent dose and
      nominal particle size in the ranges of 10.0-40.0 degrees C, 2.0-10.0, 300-720
      rpm, 1.0-15.0 g/L and 0.15-0.71 mm, respectively. The most effective parameter on
      the adsorption yield was found to be pH of the solution. Fourier transforms
      infrared and electron paramagnetic resonance spectroscopy studies were performed
      for the characterisation of the adsorption on tea waste. The experimental data
      were found to be in good agreement with the isotherm models of Freundlich,
      Halsey, Handerson and Dubinin-Radushkevich. Thermodynamic analysis showed that
      the values of Delta G and Delta H are negative. It was obtained that the
      adsorption rate can be represented very well by second-order pseudo homogeneous
      kinetic model. All the results proved that fibrous tea plant waste makes an
      excellent adsorbent for Tl-201 radionuclide.

PMID- 18814965
TI  - Molecular dynamics study of binding energies, mechanical properties, and
      detonation performances of bicyclo-HMX-based PBXs.
AB  - To investigate the effect of polymer binders on the monoexplosive, molecular
      dynamics simulations were performed to study the binding energies, mechanical
      properties, and detonation performances of the bicyclo-HMX-based polymer-bonded
      explosives (PBXs). The results show that the binding energies on different
      crystalline surfaces of bicyclo-HMX decrease in the order of (010)>(100)>(001).
      On each crystalline surface, binding properties of different polymers with the
      same chain segment are different from each other, while those of the polymers in
      the same content decrease in the sequence of PVDF>F(2311)>F(2314) approximately
      PCTFE. The mechanical properties of a dozen of model systems (elastic
      coefficients, various moduli, Cauchy pressure, and Poisson's ratio) have been
      obtained. It is found that mechanical properties are effectively improved by
      adding small amounts of fluorine polymers, and the overall effect of fluorine
      polymers on three crystalline surfaces of bicyclo-HMX changes in the order of
      (010)>(001) approximately (100). In comparison with the base explosive,
      detonation performances of the PBXs decrease slightly, but they are still
      superior to TNT. These suggestions may be useful for the formulation design of
      bicyclo-HMX-based PBXs.

PMID- 18814966
TI  - Electrocoagulation treatment of black liquor from paper industry.
AB  - The procedure of electrocoagulation is an effective, fast and economic technique
      for treatment of black liquor resulting from paper industry. The effect of
      electrolysis time, current density, type of electrode material and initial pH
      were studied in an attempt to achieve a higher removal capacity. Under the
      optimal experimental conditions (initial pH 7, t=50 min and J=14 mA cm(-2)), the
      treatment of black liquor by electrocoagulation has led to a removal capacity of
      98% of COD, 92% of polyphenols and 99% of color intensity with a good
      repeatability (R.S.D.<3%) making it possible to highlight the industrial interest
      of this electrochemical process.

PMID- 18814967
TI  - Biotreatment of an effluent from a wood laminate industry using Lentinula edodes
      UEC 2019.
AB  - The aim of this work was to evaluate the performance of the fungus Lentinula
      edodes UEC 2019 in the treatment of an effluent derived from a wood laminate
      manufacturing process. The factorial design methodology was employed to verify
      the influence of the source of nitrogen, co-substratum and treatment time
      variables on the color and total phenols reduction. Assays were conducted in
      Erlenmeyer flasks and bench bioreactor and the obtained results showed that the
      best conditions for the effluent remediation were observed when using the
      effluent itself as the nitrogen source (1g/L) and glucose (79 g/L) as co
      substratum (glucose) during a treatment period of 30 days. It was possible the
      remove 92% phenol, 97% color and reduce the COD in the bioreactor by 99% while
      controlling the temperature, pH and feeding. These results demonstrate that the
      fungus was able to use the effluent components as substrate and that it has
      potential for use in wood lamination effluent remediation.

PMID- 18814968
TI  - Animal models and the prediction of efficacy in clinical trials of analgesic
      drugs: a critical appraisal and call for uniform reporting standards.

PMID- 18814969
TI  - Conflicts of interest in pain medicine: Practice patterns and relationships with
      industry.

PMID- 18814970
TI  - Antinociceptive effect of resveratrol in carrageenan-evoked hyperalgesia in rats:
      prolonged effect related to COX-2 expression impairment.
AB  - Resveratrol is a natural polyphenol that protects from cancer and cardiovascular
      diseases. Resveratrol is able to induce apoptotic cell death and it inhibits the
      cyclooxygenase (COX) cascade. We measured the antinociceptive effect of
      resveratrol on carrageenan-induced hyperalgesia, prostaglandin-E2 (PGE2)
      concentration in CSF and COX-1/COX-2 gene expression in the spinal cord and
      dorsal root ganglion (DRG) in rats. Resveratrol induced a prolonged
      antinociceptive effect, which was correlated to the inhibition of COX-2 mRNA
      increase in DRG and cord elicited by carrageenan. An increase in the basal
      threshold of mechanical nociception was also observed with resveratrol in the
      absence of any inflammatory insult. A rapid bilateralisation of COX-2 mRNA
      production, not accompanied by a parallel increase in c-Fos expression, was
      observed in spinal cord three hours after the inflammatory insult. This increase
      in COX-2 mRNA concentration in the spinal cord on the opposite side of the
      inflammatory insult was abolished by resveratrol. In conclusion, the
      antinociceptive effect exhibited by resveratrol was related to the prevention of
      COX-2 mRNA increase induced by carrageenan. Resveratrol also prevented the
      bilateralisation of COX-2 expression. The later effect, together with the
      prolonged analgesia induced by a single injection, may be of great benefit for
      preventing chronic pain states often seen after inflammatory insults.

PMID- 18814971
TI  - Column ratio mapping: a processing technique for atomic resolution high-angle
      annular dark-field (HAADF) images.
AB  - An image processing technique is presented for atomic resolution high-angle
      annular dark-field (HAADF) images that have been acquired using scanning
      transmission electron microscopy (STEM). This technique is termed column ratio
      mapping and involves the automated process of measuring atomic column intensity
      ratios in high-resolution HAADF images. This technique was developed to provide a
      fuller analysis of HAADF images than the usual method of drawing single intensity
      line profiles across a few areas of interest. For instance, column ratio mapping
      reveals the compositional distribution across the whole HAADF image and allows a
      statistical analysis and an estimation of errors. This has proven to be a very
      valuable technique as it can provide a more detailed assessment of the sharpness
      of interfacial structures from HAADF images. The technique of column ratio
      mapping is described in terms of a [110]-oriented zinc-blende structured
      AlAs/GaAs superlattice using the 1 angstroms-scale resolution capability of the
      aberration-corrected SuperSTEM 1 instrument.

PMID- 18814972
TI  - Usefulness of rNcGRA7- and rNcSAG4-based ELISA tests for distinguishing primo
      infection, recrudescence, and chronic bovine neosporosis.
AB  - Bovine reproductive failure caused by the parasite Neospora caninum is a major
      problem and is responsible for severe economic losses worldwide. Currently,
      appropriate control measures depend on the predominant transmission route in a
      particular herd. Therefore, the development of diagnostic tools capable of
      discriminating between primo-infection, recrudescence, re-infection, and chronic
      infection is a major challenge in the serodiagnosis of bovine neosporosis. Here,
      two recombinant protein-based ELISAs utilizing the immunodominant NcGRA7 dense
      granule protein and the NcSAG4 bradyzoite stage-specific protein were developed
      and showed good diagnostic performances. Their usefulness for discerning between
      primo-infection, recrudescence, re-infection, and chronic infection was also
      studied by analyzing an appropriate panel of serum samples belonging to different
      groups of experimentally and naturally infected bovines. Our results suggest that
      anti-rNcGRA7 antibody levels may be indicative of acute infection (primo
      infection, re-infection, and recrudescence), whereas the presence of anti-rNcSAG4
      antibodies may be associated with chronic infection and could be a good indicator
      of infection establishment (tachyzoite-bradyzoite conversion). Moreover, primo
      infection associated with a Neospora-associated epidemic abortion pattern is
      characterized by the detection of anti-rNcGRA7 antibodies together with the
      absence or detection of anti-rNcSAG4 antibody levels around the cut-off point. In
      contrast, the detection of antibody levels directed against both recombinant
      proteins may be quite indicative of recrudescence or re-infection associated with
      abortion and/or vertical transmission in herds with a Neospora-associated endemic
      abortion pattern. In conclusion, both serological tests developed in the present
      study offer additional information to conventional avidity tests and,
      consequently, improve the diagnosis of bovine neosporosis with perspectives for
      control measures.

PMID- 18814973
TI  - Blocking of beta-2 adrenergic receptors hastens recovery from hypoglycemia
      associated social withdrawal.
AB  - OBJECTIVE: Hypoglycemia is associated with a variety of adverse behaviors
      including fatigue, confusion and social withdrawal. While these clinical symptoms
      are well characterized, the mechanism of their cause is not understood. Here we
      investigated how insulin-induced hypoglycemia causes social withdrawal. RESEARCH
      DESIGN AND METHODS: Male 8-12-week-old C57BL/6J mice were injected
      intraperitoneally (IP) with or without and/or insulin, norepinephrine (NE) and
      epinephrine (Epi), terbutaline and butoxamine with subsequent measurement of
      blood glucose, social withdrawal and plasma catecholamines. RESULTS: Insulin
      generated (0.75h post-injection) significant hypoglycemia with blood glucose
      nadirs of 64+/-4 and 48+/-5mg/dl for 0.8 and 1.2units/kg of insulin,
      respectively. Insulin (0.8 or 1.2units/kg) caused near total social withdrawal at
      0.75h with full recovery not occurring until 4h (0.8units/kg) or 8h (1.2units/kg)
      post-insulin injection. Insulin also caused a marked elevation in plasma
      catecholamines. Basal 12h fasting NE and Epi were 287+/-38 and 350+/-47pg/ml,
      respectively. Insulin at 0.8units/kg increased plasma NE and Epi to 994+/-73 and
      1842+/-473pg/ml, respectively. Administration of exogenous NE or Epi caused
      social withdrawal similar in magnitude to insulin. Importantly, administration of
      the beta-2 adrenergic receptor agonist terbutaline also caused social withdrawal
      while administration of the beta-2 adrenergic receptor antagonist butoxamine
      blocked NE-induced social withdrawal. Finally, butoxamine blocked insulin-induced
      social withdrawal. CONCLUSIONS: These data demonstrate that hypoglycemia
      associated social withdrawal is dependent on catecholamines via a beta-2 receptor
      mediated pathway.

PMID- 18814974
TI  - Gender differences among smokers receiving interventions for tobacco dependence
      in a medical setting.
AB  - OBJECTIVE: The purpose of this study was to assess differences between women and
      men receiving treatment for tobacco dependence through a clinical treatment
      program. METHODS: We conducted a retrospective review of clinical data collected
      on 2139 ambulatory and 1259 hospitalized smokers receiving individualized tobacco
      dependence treatment from Jan 1, 2004 to Dec 31, 2005 through the Mayo Clinic
      Nicotine Dependence Center. RESULTS: Overall, female smokers smoked less than
      males (p<0.001); were less likely to have received treatment for alcoholism
      (p<0.001); were more likely to have received treatment for past depression
      (p<0.001); were also less likely to have started smoking prior to 18 years of age
      (p=0.004 and p=0.008 for ambulatory and hospitalized patients, respectively);
      were less likely to be married (p<0.001); were less likely to be tobacco
      dependent (hospitalized smokers only p=0.04); and were more likely to have
      received a prescription for a smoking cessation medication (ambulatory smokers
      only, p=0.034). After adjustment for baseline characteristics, women and men did
      not differ in tobacco abstinence outcomes. CONCLUSION: Although many gender
      differences are present among patients treated in a large ambulatory and hospital
      based tobacco treatment programs, gender is not associated with failure to
      achieve smoking abstinence.

PMID- 18814975
TI  - Retrospective study on swine Torque teno virus genogroups 1 and 2 infection from
      1985 to 2005 in Spain.
AB  - A retrospective study to detect evidence of swine Torque teno virus (TTV)
      genogroups 1 and 2 infection in sera of pigs from the Spanish livestock between
      years 1985 and 2005 was carried out by means of PCR. Also, the molecular
      evolution of TTV genogroups 1 and 2 during the 20-year period studied using a 250
      base sequence of the non-coding region of the viral genome was assessed. Both TTV
      genogroup genomes were found in pig sera from the first year of study. Taking
      into account the whole study period, 113 out of 162 animals (69.8%) were infected
      with one or the other genogroup, while 38 out of 162 pigs (23.5%) were co
      infected with both genogroups. Moreover, TTV genogroup 2 (90 out of 162, 55.6%)
      was significantly more prevalent than genogroup 1 (54 out of 162, 33.3%). The non
      coding region of swine TTV genome sequenced showed its adequacy as a molecular
      marker in swine TTV. This study represents the earliest evidence of TTV infection
      in pigs to date, 14 years before the initial description of this virus. Moreover,
      this is also the earliest evidence of TTV infection in any species.

PMID- 18814976
TI  - Reduced variability in motor behaviour: an indicator of impaired cerebral
      connectivity?
AB  - Evidence is accumulating that abundance in cerebral connectivity is the neural
      basis of human behavioural variability, i.e., the ability to select adaptive
      solutions from a large repertoire of behavioural options. Recently it was
      demonstrated that variability in motor behaviour- the hallmark of typical
      development--emerges coincident with the onset of synaptic activity in the
      embryonic cortex. This inspired the hypothesis that variability results from
      cortical activity and that its expression depends on integrity of cortical
      connectivity. Recent findings in preterm infants with cerebral white matter
      injury and in children with autism spectrum disorder (ASD) allow the elaboration
      of this hypothesis: diffuse damage of the cerebral white matter is associated
      with an overall reduction in variability, i.e., in a reduction of movement
      complexity and variation, whereas reduction in long-distance cortical
      connectivity, as described in children with ASD, is associated with reduced
      variability, in which movement complexity may be conserved.

PMID- 18814977
TI  - Reduced Sertoli cell number and altered pituitary responsiveness in male lambs
      undernourished in utero.
AB  - The nutritional status of females during pregnancy can have profound effects on
      the fetus reproductive system development that could affect the reproductive
      potential as later as in adulthood (fetal programming). The aim of the present
      study was to examine the effects of maternal nutrient restriction imposed during
      different periods of gestation on pituitary responsiveness at different ages
      postnatal and on Sertoli cell number in male offspring. Pregnant ewes were fed to
      100% of Metabolizable Energy and Crude Protein requirements throughout pregnancy
      (Control) or to 50% from 0 to 30 (R1) or from 31 to 100 days of gestation (R2).
      Male lambs were selected and fed to appetite throughout the study. At 2, 5.5 and
      10 months of age a GnRH challenge was conducted. At slaughter (10 months) testes
      were removed and examined histologically. Maternal undernutrition did not affect
      the time of the onset of puberty, defined as the first increase in plasma
      testosterone concentrations > or =1 ng/ml. The LH and FSH response to GnRH
      challenge did not differ between groups at 2 and 5.5 months but at 10 months of
      age a higher (P<0.05) FSH response was found in R2 group. Testes weight did not
      differ between groups at slaughter. Mean Sertoli cell number was significantly
      lower in animals of R2 group compared with Control (P<0.01). A smaller
      seminiferous tubules diameter was detected in R2 group (P<0.05), while the
      diameter of the lumen was similar in all groups. Collectively, these results
      provide clear evidence for a direct effect of nutrient restriction during
      pregnancy on Sertoli cell number in adulthood. The lower number of Sertoli cells
      is the most candidate factor for the higher pituitary activity through a
      reduction in the suppressive effect of inhibin.

PMID- 18814978
TI  - Index and ring finger ratio--a new sex determinant in south Indian population.
AB  - Identification of human remains is an imperative element of any medicolegal
      investigation, and a challenging task for forensic experts and physical
      anthropologists worldwide. Three hundred adult hands (150 males and 150 females)
      belonging to south Indian population were studied to investigate sexual
      dimorphism of the index and ring finger ratio. The index and ring finger ratio is
      derived by dividing the index finger length by ring finger length. The index and
      ring finger ratio is found to be higher in females. Index and ring finger ratio <
      or =0.9700 identified 80% of males for both hands, and ratio >0.9700 identified
      74% females for the right hand and 78% for the left hand accurately. This study
      may prove useful to determine the sex of an isolated hand when it is subjected
      for medicolegal examination.

PMID- 18814979
TI  - Pathological examination of cordectomy specimens: analysis of negative resection.
AB  - OBJECTIVE: Occasionally, after performing a cordectomy to treat a T1 glottic
      tumor, the pathologist does not detect carcinomatous cells in the surgical
      specimen. This study determined how often this happens and analyzed these cases
      to identify related variables. METHODS: Forty-six patients were studied. Data on
      patient age and gender, tumor T stage and macroscopic surface extension, device
      used (laser vs. microelectrode dissection (ME)), and presence/absence of a
      negative cordectomy were compiled. We performed excisional biopsies as a
      diagnostic procedure. RESULTS: Tumor stage was carcinoma in situ (Cis; 11 cases),
      T1a (28 cases), or T1b (7 cases). Nineteen tumors were limited, and 27 were
      extensive. Twenty-one patients underwent laser surgery, and 25 had ME. There were
      12, 21, 4, and 9 types II to V cordectomies, respectively. The pathologist
      reported 15 negative cordectomies (32.6%). Only tumor extension was significantly
      associated with a negative cordectomy (p=0.047). CONCLUSION: In 32.6% of our
      cases, the excisional biopsy was diagnostic and therapeutic. This percentage rose
      to 52.6% in the cases of limited tumors. We recommend performing an excisional
      biopsy and limited resection of the surgical bed with ME or laser surgery. A
      pathologist can examine the margins to determine whether the resection should be
      extended. When choosing radiotherapy, it is better to first perform an incisional
      biopsy to obtain a diagnosis of carcinoma.

PMID- 18814980
TI  - The effects of biotin supplementation on serum and liver tissue biotinidase
      enzyme activity and alopecia in rats which were administrated to valproic acid.
AB  - Valproic acid (VPA) is a widely used and well-tolerable antiepileptic drug in
      epileptic patients. However, VPA has many side effects dose-dependent or non-dose
      dependent. It is reported that VPA treatment may lead to biotin deficiency and
      low serum and liver tissue biotinidase enzyme activity (BEA). Major clinical
      manifestations in biotin deficiency are seborrheic dermatitis, dry skin, fine and
      brittle hair, and alopecia. We aimed to investigate the effects of biotin
      supplementation on serum and liver tissue BEA and alopecia during VPA therapy.
      Rats were randomly divided into 4 groups, each consisted of 15 rats (VPA-B1, VPA
      B2, VPA, and control). Except the control group, all groups were administrated
      VPA dose of 600 mg/kg/d per oral (PO) for 60 days with 12h intervals two divided
      doses. VPA-B1 was administrated biotin dose of 6 mg/kg/d and VPA-B2 was
      administrated biotin dose of 0.6 mg/kg/d. In the third week of the study, we
      determined alopecia in the study groups. Alopecia was seen in the subjects of
      13.3% of VPA-B1 (n=2), 13.3% of VPA-B2 (n=2), and 40% of VPA (n=6). But
      statistical significant effect on alopecia by biotin supplementation was not able
      to be determined between the study groups. In the control group, alopecia was not
      observed. The ratios of alopecia in the study groups were statistically higher
      than the control group (p=0.028). Itchiness was more obvious in the study groups
      compared with the control group. Serum biotin levels of the biotin supplemented
      groups (VPA-B1 and VPA-B2) were higher than the other groups (VPA and control
      group). Serum biotin levels of the VPA group were lower than the control group.
      There were significant decreases in the levels of serum and liver tissue BEA of
      the study groups compared with the control group. In conclusion we showed that
      VPA usage reduced the serum and liver tissue BEA and impaired the biotin
      utilization by affecting the liver. Partial biotinidase deficiency may lead to
      alopecia. It might be prevented by biotin supplementation in the patients
      receiving VPA therapy. We considered that further studies are necessary to find
      out the effective and safe biotin dose.

PMID- 18814981
TI  - [Susceptibility patterns of Pseudomonas aeruginosa strains isolated in the
      Monastir region, Tunisia].
AB  - The aim of this study was to determine the susceptibility rates and patterns in
      P. aeruginosa strains isolated from 2002 to 2005 in a teaching Hospital of
      Tunisia. Susceptibility to antibiotics was assessed according to CA-SFM
      guidelines. During this period, 1368 strains of P. aeruginosa were identified,
      they were isolated mainly from pus (52.9%), respiratory samples (19.5 %), urine
      (10.6%), and blood cultures (5%). The percentages of resistant isolates were as
      follows: ticarcilline: 26.2%; ceftazidime: 21.8%; imipenem: 19.6%; gentamicin:
      39.3%; amikacin: 19.2%, and ciprofloxacin: 21.6%. Nosocomial infections in P.
      aeruginosa are responsible for important morbidity and mortality rates, the
      survey of resistance to antibiotics is necessary for an efficient treatment.

PMID- 18814982
TI  - [Annular pancreas in adults: a case report].

PMID- 18814983
TI  - Positron Emission Tomography (PET) and breast cancer in clinical practice.
AB  - The landscape of oncologic practice has changed deeply during the past few years
      and there is now a need, through a multidisciplinary approach, for imaging to
      provide accurate evaluation of morphology and function and to guide treatment
      (Image Guided Therapy). Increasing emphasis has been put on Position Emission
      Tomography (PET) role in various cancers among clinicians [Juweid ME, Cheson BD.
      Positron-emission tomography and assessment of cancer therapy. N Engl J Med
      2006;354:496-507; Koh DM, Cook GJR, Husband JE. New horizons in oncologic
      imaging. N Engl J Med 2003;348:25; Tafra L, positron emission tomography (PET)
      and mammography (PEM) for breast cancer: importance to surgeons. Ann Surg Oncol
      2006;14(1):3-13] and patients despite a general context of healthcare expenditure
      limitation. Positron Emission Tomography has currently a limited role in breast
      cancer, but also general radiologists and specialists should be aware of these
      indications, especially when staging aggressive cancers and looking for
      recurrence. Currently, the hybrid systems associating PET and Computed Tomography
      (CT) and in the same device [Rohren EM, Turkington TG, Coleman RE. Clinical
      applications of PET in oncology. Radiology 2004;231:305-32; Blodgett TM, Meltzer
      CM, Townsend DW. PET/CT: form and function. Radiology 2007;242:360-85; von
      Schulthess GK, Steinert HC, Hany TF. Integrated PET/CT: current applications and
      futures directions. Radiology 2006;238(2):405-22], or PET-CT, are more commonly
      used and the two techniques are adding their potentialities. Other techniques,
      MRI in particular, may also compete with PET in some instance and as far as
      ionizing radiations dose limitation is considered, some breast cancers becoming
      some form of a chronic disease. Breast cancer is a very complex, non-uniform,
      disease and molecular imaging at large may contribute to a better knowledge and
      to new drugs development. Ongoing research, Positron Emission Mammography (PEM)
      and new tracers, are likely to bring improvements in patient care [Kelloff GJ,
      Hoffman JM, Johnson B, et al. Progress and promise of FDG-PET Imaging for cancer
      patient management and oncologic drug development. Clin Cancer Res 2005;1(April
      (8)): 2005].

PMID- 18814984
TI  - Sulphide oxidation to elemental sulphur in a membrane bioreactor: performance and
      characterization of the selected microbial sulphur-oxidizing community.
AB  - In leather tanning industrial areas sulphide management represents a major
      problem. However, biological sulphide oxidation to sulphur represents a
      convenient solution to this problem. Elemental sulphur is easy to separate and
      the process is highly efficient in terms of energy consumption and effluent
      quality. As the oxidation process is performed by specialized bacteria, selection
      of an appropriate microbial community is fundamental for obtaining a good yield.
      Sulphur oxidizing bacteria (SOB) represent a wide-ranging and highly diversified
      group of microorganisms with the capability of oxidizing reduced sulphur
      compounds. Therefore, it is useful to select new microbes that are able to
      perform this process efficiently. For this purpose, an experimental membrane
      bioreactor for sulphide oxidation was set up, and the selected microbial
      community was characterized by constructing 16S rRNA gene libraries and
      subsequent screening of clones. Fluorescence in situ hybridization (FISH) was
      then used to assess the relative abundance of different bacterial groups.
      Sulphide oxidation to elemental sulphur proceeded in an efficient (up to 79%
      conversion) and stable way in the bioreactor. Both analysis of clone libraries
      and FISH experiments revealed that the dominant operational taxonomic unit (OTU)
      in the bioreactor was constituted by Gammaproteobacteria belonging to the
      Halothiobacillaceae family. FISH performed with the specifically designed probe
      tios_434 demonstrated that this OTU constituted 90.6+/-1.3% of the bacterial
      community. Smaller fractions were represented by bacteria belonging to the
      classes Betaproteobacteria, Alphaproteobacteria, Deltaproteobacteria, Clostridia,
      Mollicutes, Sphingobacteria, Bacteroidetes and Chlorobia. Phylogenetic analysis
      revealed that clone sequences from the dominant OTU formed a stable clade (here
      called the TIOS44 cluster), within the Halothiobacillaceae family, with sequences
      from many organisms that have not yet been validly described. The data indicated
      that bacteria belonging to the TIOS44 cluster were responsible for the oxidation
      process.

PMID- 18814985
TI  - Pharmacokinetics of gadoversetamide injection, a gadolinium-based contrast agent,
      in pediatric patients.
AB  - OBJECTIVE: The pharmacokinetics of gadoversetamide were examined in pediatric
      patients scheduled to undergo contrast-enhanced MRI of the central nervous
      system. MATERIALS AND METHODS: One hundred patients received an intravenous
      injection of gadoversetamide at a dose of 0.1 mmol/kg for a contrast-enhanced MRI
      procedure. A subpopulation of 30 patients were enrolled to evaluate the
      pharmacokinetics of gadoversetamide in patients 2-11 and 12-18 years of age.
      Serial blood and urine samples were collected before and after the administration
      of gadoversetamide. RESULTS: The terminal half-life, initial concentration and
      area under the curve assessments for gadoversetamide showed no significant
      (P>.05) differences between the age groups or the sexes. Although no sex-related
      differences occurred in the volume of distribution or clearance, significant
      (P<.05) age-related differences were found, but once corrected for body mass or
      surface area the differences were no longer significant. CONCLUSIONS: The
      pharmacokinetic behavior of gadoversetamide was not significantly altered by
      differences in age or sex in pediatric patients from 2 to 18 years of age.
      Although significant differences in volumes of distribution, and clearance
      occurred between the age groups, these differences appeared to depend on body
      size rather than on age in pediatric patients between 2 and 18 years of age.

PMID- 18814986
TI  - Whole-body T2* mapping at 1.5 T.
AB  - This study investigated the feasibility of an MRI protocol providing whole-body
      T2* maps at 1.5 T. Seven healthy volunteers (mean age=30.1+/-3.7, three women and
      four men) and two patients (both male, 53 and 46 years old) affected by
      transfusion-dependent anemias participated in the study. Coronally oriented
      images of five subsequent body levels were acquired using a fat-suppressed
      multiecho 2D gradient-echo sequence (12 echo times ranging from 4.8 to 76.3 ms
      were selected) and afterwards composed. Parametrical T2* maps of the whole body
      were reconstructed on a pixel-by-pixel basis. For both, healthy volunteers and
      patients, representative T2* values were computed from extended regions of
      interest (ROIs). Good-quality whole-body T2* maps were computed in all volunteers
      and patients. In healthy volunteers, T2* values were assessed in the cerebral
      white (58.5+/-4.2 ms) and gray (81.4+/-5.5 ms) matter, liver (34.3+/-7.0 ms),
      spleen (63.5+/-3.3 ms), kidneys (65.4+/-10.3 ms) and skeletal muscles (~30 ms).
      The liver presented faster relaxation rates in males as compared to females. One
      patient (serum ferritin concentration=927 microg/dl) showed shortened T2* values
      in liver (3.6+/-5.5 ms), spleen (3.1+/-4.8 ms), kidneys (11.1+/-7.1 ms) and
      muscles (25.1+/-3.4 ms). The second patient (serum ferritin concentration=346
      microg/dl) presented reduced T2* values in liver (3.9+/-7.3 ms), spleen (20.1+/
      9.8 ms) and kidneys (24.6+/-7.7 ms). The presented technique may find clinical
      application in the assessment of the iron burden in the entire body, and in
      monitoring of chelation therapies in patients treated with frequent blood
      transfusions.

PMID- 18814987
TI  - Structural effect on degradability and in vivo contrast enhancement of
      polydisulfide Gd(III) complexes as biodegradable macromolecular MRI contrast
      agents.
AB  - The structural effect of biodegradable macromolecular magnetic resonance imaging
      (MRI) contrast agents, polydisulfide gadolinium (Gd)(III) chelates, on their in
      vitro degradability, and cardiovascular and tumor imaging were evaluated in mice.
      Polydisulfide Gd(III) chelates, Gd-DTPA cystamine copolymers (GDCC), Gd-DTPA l
      cystine copolymers (GDCP), Gd-DTPA d-cystine copolymers (dGDCP) and Gd-DTPA
      glutathione (oxidized) copolymers (GDGP), with different sizes and narrow
      molecular weight distribution were prepared and evaluated both in vitro and in
      vivo in mice bearing MDA-MB-231 tumor xenografts. GDGP with large steric
      hindrance around the disulfide bonds had greater T(1) and T(2) relaxivities than
      GDCC, GDCP and dGDCP. The degradability of the polydisulfide by the endogenous
      thiols decreased with increasing steric effects around the disulfide bonds in the
      order of GDCC>GDCP, dGDCP>GDGP. The size and degradability of the contrast agents
      had a significant impact on vascular contrast enhancement kinetics. The agents
      with a large size and low degradability resulted in more prolonged vascular
      enhancement than the agents with a small size and high degradability. It seems
      that the size and degradability of the agents did not significantly affect tumor
      enhancement. All agents resulted in significant contrast enhancement in tumor
      tissue. This study has demonstrated that the vascular enhancement kinetics of the
      polydisulfide MRI contrast agents can be controlled by their sizes and
      structures. The polydisulfide Gd(III) chelates are promising biodegradable
      macromolecular MRI contrast agents for magnetic resonance angiography and cancer
      imaging.

PMID- 18814988
TI  - Examining the acute effects of cediranib (RECENTIN, AZD2171) treatment in tumor
      models: a dynamic contrast-enhanced MRI study using gadopentate.
AB  - Cediranib (RECENTIN, AZD2171) is a highly potent inhibitor of the tyrosine kinase
      activity associated with all three vascular endothelial growth factor (VEGF)
      receptors and is currently in Phase II/III clinical trials. Preclinically,
      cediranib inhibits VEGF signaling and angiogenesis in vivo and impedes solid
      tumor growth significantly. Clinically, changes observed using dynamic contrast
      enhanced MRI (DCE-MRI) with gadopentate suggest that acute cediranib treatment
      compromises tumor hemodynamics. In this study, a DCE-MRI baseline scan using
      gadopentate was performed in nude rats bearing Lovo (human colorectal carcinoma)
      or C6 (rat glioma) tumors. Cediranib (3 mg/kg per day) or vehicle was then dosed
      orally (2, 26 and 50 h after the baseline scan; 12 rats per group) and a second
      scan acquired 2 h after the final dosing event. Mean values for K(trans) (Tofts
      and Kermode-derived) [Magn Reson Med 17 (1991) 357-67] and the initial area under
      the gadolinium concentration curve over the first 60 s (iAUC) were reduced
      significantly following cediranib treatment: K(trans) by 33% (P<.05) in both
      tumor models and iAUC by 23% (P>.05) and 33% (P>.005) in Lovo and C6,
      respectively. This is the first preclinical investigation to examine the effect
      of cediranib treatment on tumors by DCE-MRI with gadopentate.

PMID- 18814989
TI  - A simple and rapid high-performance liquid chromatographic method for the
      determination of bisoprolol fumarate and hydrochlorothiazide in a tablet dosage
      form.
AB  - A simple and precise high performance liquid chromatographic method has been
      developed and validated for the simultaneous determination of bisoprolol fumarate
      (BF), and hydrochlorothiazide (HCTZ) in a tablet formulation. Chromatography was
      carried out at 25 degrees C on a 4.6 mm x 250 mm, 5 microm cyano column with the
      isocratic mobile phase of 0.1M aqueous phosphate buffer, acetonitrile and
      tetrahydrofuran (85:10:5, v/v/v) at a flow rate of 1.0 ml/min. The UV detection
      was carried out at 225 nm. HCTZ and BF were separated in less than 10 min with
      good resolution and minimal tailing, without interference of excipients. The
      method was validated according to ICH guidelines and the acceptance criteria for
      accuracy, precision, linearity, specificity and system suitability were met in
      all cases. The method was linear in the range of 50-150 microg/ml for BF and 125
      375 microg/ml for HCTZ.

PMID- 18814990
TI  - Tigecycline in vitro activity against commonly encountered multidrug-resistant
      gram-negative pathogens in a Middle Eastern country.
AB  - The lack of data from the Middle East warranted studying tigecycline in vitro
      activity in Lebanon against consecutive multidrug-resistant (MDR) bacteria,
      including extended-spectrum beta-lactamases producing clinical isolates of
      Escherichia coli (n = 150), Klebsiella pneumoniae (n = 100), and Acinetobacter
      spp. (n = 64) using the standard disk diffusion method. Tigecycline-resistant and
      intermediate findings were as follows: E. coli, 0% and 0%; K. pneumoniae, 3% and
      16%; and Acinetobacter spp., 0% and 2%. These values were substantially lower
      than those determined for amikacin, gentamicin, tobramycin, ciprofloxacin,
      piperacillin/tazobactam, amoxicillin/clavulanic acid, and
      trimethoprim/sulfamethoxazole. This study demonstrates the excellent activity of
      tigecycline against the increasingly encountered MDR bacteria in Lebanon. The
      introduction of this effective and viable drug for the initial or recommended
      treatment of serious infections caused by such highly resistant pathogens is an
      asset for patients in this country and elsewhere.

PMID- 18814991
TI  - Comparison of 3 swab transport systems for direct release and recovery of aerobic
      and anaerobic bacteria.
AB  - The ability to directly release 5 aerobic and 5 anaerobic bacterial strains from
      3 swab transport systems was evaluated by a time zero roll-plate method. The
      Copan ESwab (Copan Diagnostics, Murrieta, CA), a new nylon-flocked swab with
      Amies liquid medium, yielded greater organism release and recovered approximately
      10-fold more microorganisms than the Becton Dickinson (Sparks, MD) CultureSwab
      MaxV and Remel (Lenexa, KS) BactiSwab.

PMID- 18814992
TI  - Investigation of qnr and aac(6')-Ib-cr in Enterobacter cloacae isolates from
      Anhui Province, China.
AB  - Eighty-one Enterobacter cloacae isolates collected from 20 hospitals in Anhui
      Province, China, from January to August 2005 were screened for plasmid-mediated
      quinolone resistance determinants by polymerase chain reaction and sequencing.
      qnrA1, qnrB4, qnrS1, and aac(6')-Ib-cr were present in 6.2% (5/81), 6.2% (5/81),
      8.6% (7/81), and 3.7% (3/81) of those isolates, respectively.

PMID- 18814993
TI  - Aeromedical retrieval for critical clinical conditions: 12 years of experience
      with the Royal Flying Doctor Service, Queensland, Australia.
AB  - BACKGROUND: The Royal Flying Doctor Service (RFDS) has been providing emergency
      aeromedical retrieval services in Queensland, Australia since 1928. STUDY
      OBJECTIVES: This article details service and delivery structure plus a
      description of 12 years of experience managing patients with critical clinical
      conditions. METHODS: This study is a retrospective longitudinal analysis of the
      demographics and diagnostic classification of all cases of critical clinical
      severity conducted March 1, 1994 through February 28, 2006. RESULTS: There were a
      total of 72,054 retrievals, with trauma the single most common clinical
      diagnosis. There were 4259 retrievals for patients with critical clinical
      conditions (6%). The most common categories of clinical diagnosis were: trauma
      with 1493 (35.1%), respiratory diseases 1386 (32.5%), and circulatory diseases
      908 (21.3%). Trauma accounted for 69 of the 90 (77%) primary retrievals from
      locations without health care facilities. The death rate in transport was 1%,
      with most of these involving males from locations with minimal health facilities.
      CONCLUSION: The RFDS in Queensland is an effective provider of fixed-wing
      aeromedical retrieval services, operating in an unusual environment with vast
      distances, low population density, and a high number of Indigenous people.

PMID- 18814994
TI  - Colloid cyst: a case report and literature review of a rare but deadly condition.
AB  - BACKGROUND: Colloid cysts are congenital benign tumors accounting for 0.2-2% of
      all intracranial neoplasms but representing 15-20% of all intraventricular
      masses. Emergency Physicians are more likely than any other group to encounter
      patients with a colloid cyst, a rare but life-threatening condition. The most
      common presenting complaint is severe episodic attacks of headache in a frontal
      location with associated nausea and vomiting. OBJECTIVES: To describe a rare but
      potentially life-threatening cause of headache so that clinicians will rapidly
      recognize the significance of the condition and institute timely appropriate
      therapy. CASE REPORT: We describe the case of a 40-year-old man with a severe
      headache accompanied by confusion who was diagnosed with obstructive
      hydrocephalus associated with a colloid cyst in the third ventricle. CONCLUSION:
      Recognition of this rare but important diagnosis should prompt the Emergency
      Physician to obtain timely treatment so that rapid neurologic deterioration,
      herniation, and death can be prevented. A review of the pathophysiology,
      diagnosis, and current management is discussed.

PMID- 18814995
TI  - Effects of age, race, and sex on door-to-electrocardiogram time in emergency
      department non-ST elevation acute coronary syndrome patients.
AB  - BACKGROUND: Chest pain is a frequent complaint in the Emergency Department (ED),
      and an electrocardiogram (ECG) should be performed quickly to detect acute ST
      segment elevation myocardial infarction. Previous studies have demonstrated
      disparities in cardiovascular care due to factors such as age, race, or sex;
      these studies have used non-homogenous populations across multiple sites of
      treatment, which may confound their results. STUDY OBJECTIVE: Our hypothesis was
      that, within a single center, demographic characteristics would not influence
      door-to-ECG time in ED patients with non-ST elevation acute coronary syndrome
      (NSTACS). METHODS: We performed a retrospective cohort study of patients
      presenting to the ED with NSTACS, requiring ECG changes or elevated cardiac
      biomarkers for inclusion, between 2001 and 2005. Multiple variable linear
      regression was used to evaluate the impact of race, sex, and age on door-to-ECG
      time. RESULTS: There were 247 patients who met inclusion criteria over the study
      period. The mean age was 62 +/- 14 years; 159 (64%) were white, and 151 (61%)
      were male. The mean time to ECG was 25.6 +/- 32.4 min. Neither age, sex, nor race
      had a significant impact on door-to-ECG time in either univariate or multiple
      variable modeling. A full model including age, sex, and race as well as all
      potential two-way interactions had minimal predictive ability (R(2) = 0.015).
      CONCLUSION: Within a single center, demographic characteristics had no impact on
      door-to-ECG performance time. We follow with a discussion of statistical methods
      available to adjust for clustering of observations in multicenter trials.

PMID- 18814996
TI  - Teleradiology interpretations of emergency department computed tomography scans.
AB  - BACKGROUND: Teleradiologist interpretation of radiographic studies during after
      hours Emergency Department (ED) care has the potential to influence patient
      management. STUDY OBJECTIVES: We sought to characterize frequencies of
      discrepancies between teleradiology and in-house radiology interpretations for
      computed tomography (CT) scans. METHODS: We conducted a prospective observational
      study comparing teleradiologist and in-house radiologist interpretations of CT
      scans obtained between 7:00 p.m. and 7:00 a.m. from the ED at a Level I trauma
      center. For each scan, discrepancies were characterized as major, minor, or no
      discrepancy. Follow-up data were used to characterize major discrepancies.
      RESULTS: Of 787 studies sent to teleradiology, 550 were scans of the head,
      cervical spine, chest, or abdomen and pelvis. Major discrepancies were identified
      in 32 of 550 studies (5.8%; 95% confidence interval 4.1%-8.1%), including 7 of
      160 head CT scans, 1 of 29 cervical spine CT scans, 3 of 64 chest CT scans, and
      21 of 297 abdominopelvic CT scans. We attributed 8 of the 32 major discrepancies
      to a teleradiology misinterpretation, with one case leading to an adverse event.
      CONCLUSIONS: We identified major discrepancies due to teleradiologist
      misinterpretation in 8 of 550 studies, with one patient suffering an adverse
      event. Our findings support the cautious use of teleradiology interpretations.

PMID- 18814997
TI  - Postpartum preeclampsia: emergency department presentation and management.
AB  - STUDY OBJECTIVE: Postpartum preeclampsia/eclampsia is the presence of
      hypertension and proteinuria, with or without seizures, occurring up to 4 weeks
      after delivery. We describe the Emergency Department (ED) presentation, signs and
      symptoms, results of diagnostic studies, management, and outcome in a cohort of
      patients diagnosed with postpartum preeclampsia/eclampsia at our institutions,
      and use this to review the diagnosis and management of postpartum
      preeclampsia/eclampsia. METHODS: A retrospective chart review was conducted at
      two urban teaching hospitals. Twenty-two cases were identified via ICD-9
      (International Classification of Diseases, 9(th) revision) codes of discharge
      diagnoses over an 8-year period. Only those patients who initially presented to
      an ED in the postpartum period after hospital discharge were included. A
      standardized data tool was used to extract demographic data, signs and symptoms
      of preeclampsia/eclampsia, ancillary studies previously associated with eclamptic
      pathology, and outcome during admission. RESULTS: Of the 22 women, over half
      (55%) had not been diagnosed with preeclampsia in the ante- or peripartum period.
      Common prodromal symptoms and signs in the postpartum presentation included
      headache, visual changes, hypertension, edema, proteinuria, elevated uric acid,
      and elevated liver function tests. All 4 patients who seized had prodromal
      symptoms. Women presented from 3 to 10 days postpartum (median: 5 days). Only 10
      women were primiparas. Nineteen women presented with diastolic blood pressures >
      90 mm, and only 3 of these had diastolic blood pressures of 110 mm Hg or greater.
      CONCLUSIONS: Postpartum preeclampsia/eclampsia often presents to the ED without a
      history of preeclampsia during the pregnancy. Further, not all women with this
      diagnosis who present to the ED in the postpartum period will have each of the
      "classic" features of this disease, including elevated blood pressure, edema,
      proteinuria, and hyperreflexia. This report is intended to inform emergency
      physicians of the presentation of preeclampsia/eclampsia in the postpartum
      period, including symptoms of headache, vision changes, elevated blood pressure,
      or seizure up to 4 weeks after delivery.

PMID- 18814998
TI  - Asphyxiation due to dry ice in a walk-in freezer.
AB  - BACKGROUND: Exposure to a high concentration of environmental carbon dioxide
      (CO2) can result in poisoning through direct toxicity and by displacing
      atmospheric oxygen (O2). Dry ice undergoes sublimation to a gaseous state at 
      78.5 degrees C (-109.3 degrees F), which is heavier than air and can accumulate
      in dependent areas. CASE REPORT: We report the case of a 59-year-old man found in
      cardiac arrest shortly after entering a recently repaired walk-in freezer that
      contained dry ice. First responders and bystanders did not recognize the
      proximate hazardous environment but were fortunately uninjured. A careful
      Emergency Department history coupled with rapid case investigation by the Medical
      Examiner's Office led to the determination of the cause of death and the
      elimination of the ongoing hazard. CONCLUSION: This case illustrates the lethal
      consequences of improper storage of dry ice and the need to consider toxic
      environmental exposure as a cause of sudden cardiac arrest.

PMID- 18814999
TI  - Peritoneal fluid cultures rarely alter management in patients with ascites.
AB  - STUDY OBJECTIVE: The objective of this study is to determine if the peritoneal
      fluid culture results in the ascites patient being evaluated for spontaneous
      bacterial peritonitis (SBP) in the Emergency Department (ED) are used by the
      inpatient physician to appropriately alter empiric antibiotic treatment. METHODS:
      We performed a retrospective study of all ascitic fluid samples sent from the ED
      between January 1, 2002 and December 31, 2004. Exclusion criteria included
      peritoneal fluid samples sent from peritoneal dialysis patients and those
      undergoing diagnostic peritoneal lavage for trauma. Medical records were examined
      to determine culture results, initial antibiotic choices, and subsequent changes
      in antibiotics by the inpatient physician in response to the culture results. The
      primary outcome measure was the percentage of cases in which ED peritoneal fluid
      culture results caused inpatient physicians to appropriately change antibiotic
      coverage. RESULTS: There were 201 ascitic fluid samples, of which 7 (3.5%; 95%
      confidence interval [CI] 1.4%-7.0%) had a pathogen identified. Of these, only 1
      (0.5%; 95% CI .01%-2.4%) resulted in an appropriate change in empiric antibiotic
      therapy. Although there were additional opportunities for appropriately using the
      culture results to change the antibiotic coverage in 2 (1%; 95% CI 0.1%-3.6%)
      patients, coverage was not changed. In fact, it was changed inappropriately in
      these 2 patients, and in an additional patient on appropriate empiric therapy.
      CONCLUSIONS: The yield from ascitic fluid cultures was low, and when positive,
      did not appropriately change management according to microbiologic criteria.

PMID- 18815000
TI  - A severe sore throat in a middle-aged man: calcific tendonitis of the longus
      colli tendon.
AB  - BACKGROUND: Neck pain is a common presentation to the Emergency Department (ED),
      requiring appropriate evaluation to exclude serious pathology. OBJECTIVES: To
      review an atypical clinical presentation of neck pain and to distinguish this
      case and its associated radiographic features from more common clinical entities.
      CASE REPORT: We present an ED case of calcific tendonitis of the longus coli
      muscle. SUMMARY: Acute calcific retropharyngeal tendinitis is a rare, benign
      etiology of non-traumatic neck pain that is poorly recognized and often mistaken
      for other conditions secondary to infection or trauma. The importance of this
      disorder, as well as a review of the literature on the subject, is presented.

PMID- 18815001
TI  - Axillary artery injury secondary to inferior shoulder dislocation.
AB  - BACKGROUND: Dislocation injuries of the glenohumeral joint are common in the
      general public and generally are corrected without complication. One serious
      complication with shoulder dislocations, or the subsequent reduction, is a lesion
      to the axillary artery. This specific complication is most frequently seen in the
      elderly population, where vascular structures have become less flexible. Also,
      these injuries are most common in association with anterior dislocations of the
      shoulder. OBJECTIVES: To bring awareness to the possibility of axillary artery
      injury with inferior dislocation of the shoulder, the treatment options, and a
      review. CASE REPORT: We report a 15-year-old male athlete who inferiorly
      dislocated his shoulder during wrestling practice. The injury was reduced at the
      scene with manual traction and the patient was transferred to our clinic for
      evaluation. The patient was determined to have a pseudoaneurysm of the axillary
      artery, and the history and treatment of the illness are presented. CONCLUSION:
      Axillary artery injuries secondary to shoulder dislocations are rare, especially
      in the young athlete, and proper recognition and treatment offer patients a full
      recovery.

PMID- 18815002
TI  - Anion gap as a screening tool for elevated lactate in patients with an increased
      risk of developing sepsis in the Emergency Department.
AB  - OBJECTIVES: Serum lactate levels are a useful tool in monitoring critically ill
      patients, especially those who are septic. However, lactate levels are often not
      routinely drawn or rapidly available in some institutions. The objective of this
      study was to determine if a readily available anion gap (AG) could be used as a
      surrogate marker for abnormal lactate level in Emergency Department (ED) patients
      at risk for sepsis. METHODS: Prospective, observational cohort study of
      consecutive ED patients seen at an urban university tertiary care referral center
      with 46,000 annual ED visits. ED patients aged 18 years or older presenting with
      clinically suspected infection were eligible for enrollment if a serum chemistry
      and lactate levels were drawn during the ED visit. During the 9-month study
      period, 1419 patients were enrolled. The initial basic chemistry panels,
      calculated AG, and lactate levels drawn in the ED were collected. We defined, a
      priori, an AG > 12 and a lactate > 4 mmol/L to be abnormal. Analysis was
      performed with Student's t-test, operating characteristics with 95% confidence
      intervals, and logistic regression. RESULTS: The mean AG was 11.8 (SD 3.6) and
      the mean lactate was 2.1 (SD 1.3). For an AG > 12, the mean lactate was 2.9 (SD
      1.7), compared with 1.8 (SD 0.8) for an AG < 12. The sensitivity of an elevated
      AG (> 12) in predicting elevated lactate levels (> 4 mmol/L) was 80% (72-87%) and
      the specificity was 69% (66-71%). Patients with a gap > 12 had a 7.3-fold (4.6
      11.4) increased risk of having a lactate > 4 mmol/L. The area under the curve was
      0.84. CONCLUSION: This study suggests that an elevated AG obtained in the ED is a
      moderately sensitive and specific means to detect elevated lactate levels in ED
      patients at risk for sepsis. This information may be somewhat helpful to
      Emergency Physicians to risk-stratify their patients to provide more aggressive
      early resuscitation.

PMID- 18815003
TI  - Metastatic laryngeal carcinoma with acute airway compression.

PMID- 18815004
TI  - Illness perceptions in patients with fibromyalgia.
AB  - OBJECTIVE: Former studies in chronic diseases showed the importance of patients'
      beliefs and perceptions. The Revised Illness Perception Questionnaire was
      developed to assess these illness perceptions. Our goal was to investigate
      psychometric properties of the IPQ-R for Fibromyalgia Dutch language version (IPQ
      R FM-Dlv) and to describe illness perceptions of participants with FM. METHODS:
      196 patients completed the IPQ-R FM-Dlv. Internal consistency, domain structure
      and inter domain correlations were calculated and compared to the IPQ-R English
      language version. Scores were compared with chronic fatigue syndrome (CFS),
      rheumatoid arthritis (RA), and coronary heart disease (CHD). RESULTS: Most
      psychometric properties were comparable to those of the original IPQ-R.
      Participants showed a lack of understanding of their illness, expected their FM
      to be chronic and to have a lot of negative consequences on functioning. In 17
      out of 24 domains significant differences were found between FM and CFS, RA, and
      CHD patients. CONCLUSION: The IPQ-R FM-Dlv showed acceptable psychometric
      properties, although some aspects need closer examination. Illness perceptions of
      FM patients on the Dutch questionnaire were non-comparable to CFS, RA, and CHD
      patients on the English questionnaire. PRACTICE IMPLICATIONS: The IPQ-R FM-Dlv
      can be used to assess illness perceptions of Dutch FM patients.

PMID- 18815005
TI  - Histological and sex steroid hormone receptor changes in testes of immature,
      mature, and aged chickens.
AB  - Sex steroid hormone receptors play a central role in the regulation of
      reproduction in male chickens. In this work, we evaluated by histomorphometric
      methods and Western blot analysis changes in the number of the different cell
      populations and in the content of sex steroid hormone receptors in testes from
      immature (1.5-month-old), mature (12-month-old), and aged (48-month-old)
      chickens. The number of Sertoli cells, germ cells, and Leydig cells per area of
      testicular tissue markedly changed according to chicken age. The highest number
      of Sertoli and Leydig cells was found in testes of immature chickens, with a
      dramatic decrease in those of mature chickens; however, the number of germ cells
      was the highest in mature chickens in comparison with other ages. The content of
      androgen receptor diminished in testes of mature and aged animals in comparison
      with that of immature chickens. In contrast, the content of estrogen receptor
      alpha and progesterone receptor was higher in testes of mature animals than in
      other ages. Both progesterone receptor isoforms were expressed in a similar
      proportion in testes of immature and mature animals. Interestingly, progesterone
      receptor isoform A was the predominant isoform in aged animals. These results
      suggest that there are marked age-dependent changes in chicken testes histology
      and in sex steroid hormone receptors content that should contribute to sex
      steroid hormone actions, in this tissue throughout the lifespan of chickens.

PMID- 18815006
TI  - Generalized anxiety disorder in a nonclinical sample of children: symptom
      presentation and predictors of impairment.
AB  - Presentation of generalized anxiety disorder (GAD) in a nonclinical sample of
      children (7-11 years old) and factors that predict overall impairment were
      examined. Symptom presentation was compared in children with GAD (n=49) and
      anxious children without GAD (n=42). Children with GAD endorsed significantly
      more worries, greater intensity of worries, and more DSM-IV associated symptoms
      than anxious children without GAD. Eighty-six percent of children with GAD had a
      comorbid diagnosis with 4% having a depressive disorder. Number of associated
      symptoms was most predictive of GAD impairment based on child perspective and
      intensity of worry was most predictive based on clinician perspective. Overall,
      findings from the current study are consistent with reports based on clinical
      samples. The DSM-IV-TR criteria for GAD were supported, with the exception that
      children with GAD typically present with several associated symptoms, rather than
      only one.

PMID- 18815007
TI  - Carotid chemodectomas: long-term results of subadventitial resection with
      deliberate external carotid resection.
AB  - The aim of this study was to evaluate the short-term and long-term results of the
      subadventitial resection of carotid chemodectomas and to validate the importance
      of deliberate resection of the external carotid artery (ECA). From 1981 to 2006,
      39 carotid chemodectomas of the carotid bifurcation or of the neighboring nerves
      were operated on in our department. There were 14 men and 22 women, with a mean
      age 44.4 +/- 5 (range 21-78) years. One of these operations was a redo surgery
      for local recurrence. One female patient presented with a bilateral tumor. Two
      tumors were secreting catecholamines. All these tumors affected the carotid body;
      10 of them were also affecting the vagus nerve, and one among these last 10
      affected the sympathetic nerve as well. In 11 cases, the tumor had spread into
      the subparotidal space and, in one case, into the skull. In two cases, the tumor
      had been revealed by hemispheric ischemia and in every case by tumoral syndrome.
      All the patients were followed up by clinical examination, duplex scan, or
      computed tomographic scan until the end of 2006. In 38 cases, complete resection
      was performed; an incomplete resection was performed in one case with cranial
      invasion. Under general anesthesia, and most of the time without pharmaceutical
      preparation, surgery consisted of a deliberate sacrifice of the ECA followed by
      subadventitial resection of the tumor. In one case, a previous embolization had
      been carried out to facilitate the cleavage, which in fact rendered it more
      complicated. In 22 cases, resection concerned the ECA; in seven cases, it
      concerned the common carotid artery and the internal carotid artery (ICA): in
      seven cases the superior laryngeal nerve, in nine cases the vagus nerve, in five
      cases the sympathetic nerve, and in four cases the jugular vein. In 13 cases,
      node clearing was associated. In 20 cases, an additional vascular procedure was
      performed: nine dilatations for spasm of the ICA, five autogenous vein grafts,
      two prosthetic bypasses, and one endarterectomy associated with a patch
      angioplasty. All patients were followed up until 2006. At 3 months, the observed
      complications were the sequelae of a homolateral hemispheric accident due to
      thrombosis of a vein graft, eight peripheral facial nerve palsies, 12 vocal
      palsies, seven Claude Bernard-Horner (CBH) syndromes, eight palatal paralyses,
      and 10 nociceptive pains. Some of these complications did persist: nine vocal
      cord paralyses that were successfully treated by speech therapy, three mild CBH
      syndromes, and nociceptive pains in 6% of the cases (15.4%), incapacitating in
      one case. With a follow-up of 115 +/- 27 (range 1-298) months, three local
      recurrences were recorded at 6 and 10 years. In two cases, local recurrence
      occurred when initial resection of the ECA had not been performed. Two patients
      presented with a contralateral lesion, at 12 and 16 years, respectively. At 40
      months, one patient had to be reoperated on for an atheromatous stenosis. At 51
      months, a female patient's death was not related to the operation. Subadventitial
      resection of carotid body tumors with deliberate resection of the ECA is a simple
      and efficient procedure. It is the preferential treatment for these slow-growing
      localized tumors.

PMID- 18815008
TI  - Implementing eigenvector methods/probabilistic neural networks for analysis of
      EEG signals.
AB  - A new approach based on the implementation of probabilistic neural network (PNN)
      is presented for classification of electroencephalogram (EEG) signals. In
      practical applications of pattern recognition, there are often diverse features
      extracted from raw data which needs recognizing. Because of the importance of
      making the right decision, the present work is carried out for searching better
      classification procedures for the EEG signals. Decision making was performed in
      two stages: feature extraction by eigenvector methods and classification using
      the classifiers trained on the extracted features. The aim of the study is
      classification of the EEG signals by the combination of eigenvector methods and
      the PNN. The purpose is to determine an optimum classification scheme for this
      problem and also to infer clues about the extracted features. The present
      research demonstrated that the power levels of the power spectral density (PSD)
      estimates obtained by the eigenvector methods are the features which well
      represent the EEG signals and the PNN trained on these features achieved high
      classification accuracies.

PMID- 18815009
TI  - Emotional balances in experimental consumer choices.
AB  - This paper presents an experiment, which builds a bridge over the gap between
      neuroscience and the analysis of economic behaviour. We apply the mathematical
      theory of Pavlovian conditioning, known as Recurrent Associative Gated Dipole
      (READ), to analyse consumer choices in a computer-based experiment. Supplier
      reputations, consumer satisfaction, and customer reactions are operationally
      defined and, together with prices, related to READ's neural dynamics. We recorded
      our participants' decisions with their timing, and then mapped those decisions on
      a sequence of events generated by the READ model. To achieve this, all constants
      in the differential equations were determined using simulated annealing with data
      from 129 people. READ predicted correctly 96% of all consumer choices in a
      calibration sample (n=1290), and 87% in a test sample (n=903), thus outperforming
      logit models. The rank correlations between self-assessed and dipole-generated
      consumer satisfactions were 89% in the calibration sample and 78% in the test
      sample, surpassing by a wide margin the best linear regression model.

PMID- 18815010
TI  - An examination of MUTED as a schizophrenia susceptibility gene.

PMID- 18815011
TI  - Interaction between SERTPR and stressful life events on response to
      antidepressant treatment.
AB  - A polymorphism within the serotonin transporter gene (SERTPR) has been repeatedly
      associated to mood disorders and response to SSRIs treatment. Recent evidence
      suggested that influence of genetic effect of SERTPR might be modulated by
      stress, particularly as regard the development of anxious-depressive symptoms.
      Nevertheless, there is no information about the role of stressors as potential
      modulator of SERTPR effects on depressive outcome during pharmacological
      treatment. In a sample of 159 mood disorder patients treated with fluvoxamine, we
      found stressors preceding the onset of the illness significantly influencing the
      genetic effect exerted by SERTPR on response after 6 weeks of treatment. This
      preliminary finding supports the idea of complex interaction between biological
      and environmental factors underlying the efficacy of biological treatments, other
      than liability for mood disorders. Nevertheless, many limitations characterize
      the present investigation and well-funded studies on larger samples are required.

PMID- 18815012
TI  - Solid-state NMR spectroscopy using the lost I spin magnetization in polarization
      transfer experiments.
AB  - A variation of the cross polarization (CP) experiment is discussed. The method
      requires two scans where the difference signal is equivalent to the I spin
      magnetization that is transferred to the S spins. The acquired signal is
      equivalent to F1 sum projection of a two-dimensional (2D) heteronuclear
      correlation experiment and is obtained by just two scans without the need to
      increment the indirect time domain t(1). Any polarization transfer method and any
      kind of spin manipulations during the t(1) incrementation period of a 2D NMR
      experiment can be applied. The method allows fast measurements of the CP
      transfer, particularly if various S spins signal overlap and is good for spectral
      editing of I spin signals with contact to S spins. Various examples for
      biomaterials are presented. Most importantly, this novel approach is ideal for
      detailed investigations of organic-mineral interfaces in bone, here demonstrated
      for O-phospho-l-serine as simple model compound.

PMID- 18815013
TI  - Spring constants and adhesive properties of native bacterial biofilm cells
      measured by atomic force microscopy.
AB  - Bacterial biofilms were imaged by atomic force microscopy (AFM), and their
      elasticity and adhesion to the AFM tip were determined from a series of tip
      extension and retraction cycles. Though the five bacterial strains studied
      included both Gram-negative and -positive bacteria and both environmental and
      laboratory strains, all formed simple biofilms on glass surfaces. Cellular spring
      constants, determined from the extension portion of the force cycle, varied
      between 0.16+/-0.01 and 0.41+/-0.01 N/m, where larger spring constants were
      measured for Gram-positive cells than for Gram-negative cells. The nonlinear
      regime in the extension curve depended upon the biomolecules on the cell surface:
      the extension curves for the smooth Gram-negative bacterial strains with the
      longest lipopolysaccharides on their surface had a larger nonlinear region than
      the rough bacterial strain with shorter lipopolysaccharides on the surface.
      Adhesive forces between the retracting silicon nitride tip and the cells varied
      between cell types in terms of the force components, the distance components, and
      the number of adhesion events. The Gram-negative cells' adhesion to the tip
      showed the longest distance components, sometimes more than 1 microm, whereas the
      shortest distance adhesion events were measured between the two Gram-positive
      cell types and the tip. Fixation of free-swimming planktonic cells by NHS and EDC
      perturbed both the elasticity and the adhesive properties of the cells. Here we
      consider the biochemical meaning of the measured physical properties of simple
      biofilms and implications to the colonization of surfaces in the first stages of
      biofilm formation.

PMID- 18815014
TI  - Surface modifications of Nitinol for biomedical applications.
AB  - Cathodic electrophoretic deposition (EPD) has been utilized for the fabrication
      of composite films for the surface modification of NiTi shape memory alloys
      (Nitinol). In the proposed method, chitosan (CH) was used as a matrix for the
      incorporation of other functional materials, such as heparin, hydroxyapatite and
      bioglass. Chitosan-heparin films were deposited from solutions of non
      stoichiometric chitosan-heparin complexes. It was found that the addition of
      anionic heparin to the solutions of cationic chitosan resulted in a significant
      increase in the cathodic deposition rate. The thickness of the films prepared by
      this method varied in the range of 0.1-3 microm. The ability of the chitosan
      heparin films to bind antithrombin, as measured by binding of (125)I-radiolabeled
      antithrombin, was much greater than that of pure chitosan films. Composite
      chitosan-hydroxyapatite films, with thickness of 1-30 microm, were obtained as
      monolayers or laminates, containing chitosan-hydroxyapatite layers, separated by
      layers of pure chitosan. The hydroxyapatite nanoparticles showed preferred
      orientation in the chitosan matrix with the c-axis parallel to the substrate
      surface. The films showed corrosion protection of the Nitinol substrates in
      Ringer's physiological solutions. The feasibility of the fabrication of composite
      films containing hydroxyapatite and bioglass in the chitosan matrix has been
      demonstrated. The method offers the advantages of room temperature processing.
      The deposition mechanisms and possible applications of the films are discussed.

PMID- 18815015
TI  - Static adhesion of cancer cells to glass surfaces coated with glycosaminoglycans.
AB  - Using a previously described method for the functionalization of glass substrates
      with glycosaminoglycans (GAGs), in vitro experimental comparison of adhesion
      levels of cancer cells to glycosaminoglycan-modified substrates was performed
      with non-treated and heparin-treated human cancer cells of different metastatic
      activity. For both non-treated and heparin-treated cells, our results indicate
      that heparan sulfate is the preferred substrate for adhesion while keratan
      sulfate shows anti-adhesive properties. The observed net effect of heparin is a
      cell-dependent reduction in the adhesion figures. Overall, our results suggest
      that tissues with higher composition of heparan sulfate chains may be
      preferential metastatic targets and indicate that the effective use of heparin as
      anti-metastatic or anti-inflammatory agent may also depend on glycosaminoglycan
      composition of the affected organs.

PMID- 18815016
TI  - Using brachial-ankle pulse wave velocity to associate arterial stiffness with
      cardiovascular risks.
AB  - BACKGROUND AND AIMS: This study aimed to elucidate the relationship between
      brachial-ankle pulse wave velocity (baPWV) and conventional cardiovascular risk
      factors. METHODS AND RESULTS: A total of 192 subjects with low to intermediate
      risk was enrolled in a cardiovascular evaluation program. A multiple regression
      model was built to find significant cardiovascular biomarkers for predicting
      baPWV. A logistic regression model was developed to associate baPWV and other
      biomarkers with the risk of cardiac diastolic dysfunction. A total of 123 men
      (mean age: 52.6+/-12.0) and 69 women (mean age: 51.7+/-10.4) was included. Age,
      blood pressure, C-reactive protein, serum homocysteine, heart rate, and blood
      urea nitrogen were positively predictive of increased pulse wave velocity. In
      turn, baPWV increased the risk (odds ratio: 1.257 for each m/s, 95% CI: 1.105
      approximately 1.430, p<0.001) and high-density lipoprotein decreased the risk for
      cardiac diastolic dysfunction (0.962 for each mg/dl, 95% CI: 0.925 approximately
      1.000, p=0.05). The correlation between baPWV and Framingham 10-year risk was
      moderate (men: r=0.306, p=0.002; women r=0.548, p<0.001). CONCLUSION: The results
      suggest that baPWV is a composite risk factor for early atherosclerotic change
      and a predictor for the development of diastolic dysfunction and long-term
      cardiovascular risk.

PMID- 18815017
TI  - Cranial shape differentiation in three closely related delphinid cetacean
      species: insights into evolutionary history.
AB  - The present study investigates the pattern of differentiation of cranial shape in
      three closely related delphinid cetacean species of the complex Delphinus
      Stenella-Tursiops: Delphinus delphis, Stenella coeruleoalba and Tursiops
      truncatus. Dorsal and ventral aspects of the cranium were analysed using landmark
      based geometric morphometric methods. While there was no evidence of sexual
      dimorphism for shape or size, multivariate statistical analyses showed that there
      were interspecific differences in skull morphology. Skull shape differences
      between the three studied species were related with cranial width and differences
      in the length of the rostrum relative to the cranial portion of the skull. D.
      delphis and S. coeruleoalba showed high cranial shape similarity, which is
      indicative of their evolutionary proximity when compared with T. truncatus.
      Phenetic clusters based on cranial shape similarities were found to be concordant
      with the molecular phylogenetic clades obtained from mitochondrial DNA genes.
      Geometric morphometric methods can thus be an exceptionally useful tool for the
      study of differentiation of delphinid cetacean species and therefore provide some
      insights into their evolutionary history.

PMID- 18815018
TI  - Willow bark extract (Salicis cortex) for gonarthrosis and coxarthrosis--results
      of a cohort study with a control group.
AB  - STUDY OBJECTIVE: The examination of the effectiveness and tolerance of willow
      bark extract in patients with gonarthrosis and coxarthrosis compared to
      conventional therapies. METHODS: In an open, multicentric observational study
      with reference treatment, 90 patients were treated with a standardised willow
      bark extract preparation, 41 patients with a standard therapy prescribed by a
      doctor and 8 patients with a combination of the two. After 3 and finally 6 weeks
      the effectiveness and tolerance were determined by the doctor (clinical findings,
      recording of adverse events, global tolerance) and by the patients (WOMAC
      questions concerning pain and stiffness, questions on general state of health).
      RESULTS: A total of 88 patients in the willow bark group and 40 patients in the
      reference group completed the study. The doctors and patients judged the
      effectiveness in both groups to be comparable. After 6 weeks the effectiveness of
      the willow bark extract tended to be assessed as better than in the group
      undergoing conventional therapy. Also in the subgroup of chronically sick
      patients (>3 months), after 6 weeks the effectiveness of both forms of treatment
      was comparable; however, the effect was slower to set in the willow bark group
      than in the reference group. Doctors and patients assessed the tolerance of the
      willow bark extract to be better than the conventional therapy. Adverse effects
      of the drugs did not occur in the willow bark group; one case each of reflux
      symptoms occurred in the reference group and the CONCLUSIONS: For treating mild
      or fairly severe cases of gonarthrosis and coxarthrosis the effect of willow bark
      extract is comparable to that of standard therapies, without the corresponding
      side effects having to be accepted.

PMID- 18815019
TI  - Achieving asthma control in practice: understanding the reasons for poor control.
AB  - Achieving asthma control remains an elusive goal for the majority of patients
      worldwide. Ensuring a correct diagnosis of asthma is the first step in assessing
      poor symptom control; this requires returning to the basics of history taking and
      physical examination, in conjunction with lung function measurement when
      appropriate. A number of factors may contribute to sub-optimal asthma control.
      Concomitant rhinitis, a common co-pathology and contributor to poor control, can
      often be identified by asking a simple question. Smoking too has been identified
      as a cause of poor asthma control. Practical barriers such as poor inhaler
      technique must be addressed. An appreciation of patients' views and concerns
      about maintenance asthma therapy can help guide discussion to address perceptual
      barriers to taking maintenance therapy (doubts about personal necessity and
      concerns about potential adverse effects). Further study into, and a greater
      consideration of, factors and patient characteristics that could predict
      individual responses to asthma therapies are needed. Finally, more clinical
      trials that enrol patient populations reflecting the real world diversity of
      patients seen in clinical practice, including wide age ranges, presence of
      comorbidities, current smoking, and differing ethnic origins, will contribute to
      better individual patient management.

PMID- 18815020
TI  - Genetic variation of IL13 as a risk factor of reduced lung function in children
      and adolescents: a cross-sectional population-based study in Korea.
AB  - BACKGROUND: Previous investigations have suggested that genetic variations are
      associated with reduced lung function in early childhood. This study was
      conducted to evaluate the association between IL13+2044G-->A, the functionally
      relevant single nucleotide polymorphism (SNP) in the gene coding IL13, and lung
      function in early childhood. PATIENTS AND METHODS: A total of 1900 subjects aged
      10-18 years living in Korea, were randomly recruited. Lung function test and
      methacholine bronchial provocation test were performed. Multiple regression
      analysis adjusting for sex, age, height, atopy, and history of passive smoking
      was done to evaluate effect of IL13+2044G-->A on lung function. RESULTS: Mean (+/
      SD) forced expiratory volume in 1 s (FEV(1)) was 2.66 L (+/-0.60) in subjects
      with the AA or AG genotype (n=982) and 2.75 L (+/-0.57) in subjects with the GG
      genotype (n=918). IL13+2044G-->A showed a significant association with FEV(1) [in
      the minor allele dominant model (GG vs. AG+AA), P<0.001]. Interestingly, the
      association between FEV(1) and IL13+2044G-->A remained still significant in
      subgroup analysis according to the presence of AHR (P<0.001 in subjects without
      AHR and P=0.002 in subjects with AHR). Moreover, FEV(1)/FVC (forced vital
      capacity) ratio also showed a significant association with IL13+2044G-->A in both
      groups (P<0.001 in subjects without AHR and P<0.001 in subjects with AHR). This
      cross-sectional study demonstrates that IL13+2044G-->A is significantly
      associated with a reduced lung function in Korean children and adolescents.

PMID- 18815021
TI  - Occupational hazard: treating cocaine body packers in Caribbean countries.
AB  - Body packing is a common method of smuggling cocaine where individuals ingest
      several drug-filled parcels for transport. When identified by the authorities,
      body packers are usually taken to hospital for evaluation. There are several
      points during management of these patients when the health care team may be
      placed at risk. We explore the hazards encountered during the management of these
      patients in developing Caribbean nations.

PMID- 18815022
TI  - Geotechnical properties of fresh municipal solid waste at Orchard Hills Landfill,
      USA.
AB  - This paper presents the results of a laboratory investigation to determine the
      geotechnical properties of fresh municipal solid waste (MSW) collected from the
      working phase of Orchard Hills Landfill located in Davis Junction (Illinois,
      USA). Laboratory testing was conducted on shredded MSW to determine the
      compaction, hydraulic conductivity, compressibility, and shear strength
      properties at in-situ gravimetric moisture content of 44%. In addition, the
      effect of increased moisture content during leachate recirculation on
      compressibility and shear strength of MSW was also investigated by testing
      samples with variable gravimetric moisture contents ranging from 44% to 100%.
      Based on Standard Proctor tests, a maximum dry density of 420 kg/m(3) was
      observed at 70% optimum moisture content. The hydraulic conductivity varied in a
      wide range of 10(-8)-10(-4)m/s and decreased with increase in dry density.
      Compression ratio values varied in a close range of 0.24-0.33 with no specific
      trend with the increase in moisture content. Based on direct shear tests, drained
      cohesion varied from 31 to 64 kPa and the drained friction angle ranged from 26
      to 30 degrees. Neither cohesion nor friction angle demonstrated any correlation
      with the moisture content, within the range of moisture contents tested. The
      consolidated undrained triaxial shear tests on saturated MSW showed the total
      strength parameters (c and phi) to be 32 kPa and 12 degrees, and the effective
      strength parameters (c' and phi') to be 38 kPa and 16 degrees. The angle of
      friction (phi) decreased and cohesion (c) value increased with the increase in
      strain. The effective cohesion (c') increased with increase in strain; however,
      the effective angle of friction (phi') decreased first and then increased with
      the increase in strain. Such strain-dependent shear strength properties should be
      properly accounted in the stability analysis of bioreactor landfills.

PMID- 18815023
TI  - Rapid and separation-free sandwich immunosensing based on accumulation of
      microbeads by negative-dielectrophoresis.
AB  - We report here a rapid and separation-free immunoassay using a dielectrophoresis
      (DEP) device consisting of an interdigitated microarray (IDA) electrode and a
      polydimethylsiloxane (PDMS) substrate. On applying an AC voltage to the IDA in a
      negative-DEP (n-DEP) frequency region, goat anti-mouse immunoglobulin (anti-mouse
      IgG)-immobilized microbeads moved to the surface of the PDMS substrate placed
      above the IDA. The microbeads accumulated at designated areas of the PDMS surface
      that had been precoated with anti-mouse IgG. When the fluorescence microbeads
      bearing anti-mouse IgG were suspended in an analyte (mouse IgG) solution, the
      microbeads trapped the analyte to form immunocomplexes on microbeads. The
      microbeads reacted with mouse IgG accumulated and were captured at the designated
      areas of the PDMS surface via an antibody-antigen-antibody (sandwich) reaction.
      The captured microbeads were detected selectively by fluorescence measurements at
      the focused designated areas, regardless of the presence of uncaptured microbeads
      suspended in solution. Thus, the separation and washing-out steps usually
      required for conventional immunoassay are eliminated in the presented procedure.
      Since the formation of the sandwich structures was accelerated significantly by n
      DEP, a period as short as 30s was sufficient to detect the immunoreaction at the
      surface. The fluorescence intensity of the captured microbeads at the designated
      areas increased with analyte concentration in the range 0.01-10ng/mL. The present
      procedure therefore yields a rapid, sensitive, and separation-free immunoassay in
      a simple device.

PMID- 18815024
TI  - Construction, assembling and application of a trehalase-GOD enzyme electrode
      system.
AB  - Trehalose is a disaccharide important in foods, serving as a glucose source in
      many and also as an additive in the food preparation. Because of its peculiar
      physico-chemical properties it plays an important role as preservative in drying
      and deep-freezing treatments. A new biosensor for trehalose determination has
      been realized by means of a flow system, based on a reactor in which the
      trehalase enzyme catalyses its hydrolysis into two alpha,d-glucose molecules, and
      a GOD (glucose oxidase) amperometric biosensor is employed for the glucose
      determination. The optimum operative conditions have been laid out and a
      particular attention has been paid to the immobilization procedure of the two
      enzymes. The electrode used is of the SPE (screen-printed electrode) type and has
      been activated with the Prussian Blue (PB) and then assembled using GOD
      immobilized with Nafion. The reactor has been prepared with the trehalase enzyme
      chemically immobilized on an Immunodyne ABC membrane. As demonstration of its
      utility, the biosensor has been tested on a real sample of Boletus edulis
      mushroom.

PMID- 18815025
TI  - Fully reversible optical biosensors for uric acid using oxygen transduction.
AB  - An optical biosensor is presented for continuous determination of uric acid. The
      scheme is based on the measurement of the consumption of oxygen during the
      oxidation of uric acid that is catalyzed by the enzyme uricase. The enzyme is
      immobilized in a polyurethane hydrogel next to a metal-organic probe whose
      fluorescence is quenched by oxygen. The consumption of oxygen was followed by
      measurement of changes of luminescence intensity of two kind of probes and can be
      related to the concentration of uric acid. Analytical ranges (0-2mM), the
      response times (80-100s), reproducibility, and long-term stability were
      investigated. The biosensors are stable for at least 1 month and are not
      interfered by common interferents. One kind of biosensor was applied to the
      determination of uric acid in human blood serum. The results agree with those of
      a commercial colorimetric detection kit.

PMID- 18815026
TI  - The effect of different substrates and humic acid on power generation in
      microbial fuel cell operation.
AB  - Electricity production from acetate, glucose and xylose with humic acid as
      mediator was investigated in two chambers microbial fuel cells (MFCs). Acetate
      produced the highest voltage (570 mV with 1000 Omega) and maximum power density
      (P(maxd)=123 mW/m(2)) due to a simpler metabolism than with glucose and xylose.
      Glucose and xylose resulted in P(maxd) of 28 mW/m(2) and 32 mW/m(2) at lower
      voltage of 380 mV and 414 mV, respectively. P(maxd) increased by 84% and 30%, for
      glucose and xylose respectively, when humic acid (2g/l) was present in the
      medium. No significant effect was found with acetate since the internal
      resistance possessed a limiting effect. The increase of P(maxd) due to humic acid
      presence was attributed to its ability to act as mediator. Even though pH
      decreased to 5 with glucose and xylose, due to production of acetate and
      propionate, the voltage remained on the same level of 250-350 mV.

PMID- 18815027
TI  - Biodegradation of diesel/biodiesel blends by a consortium of hydrocarbon
      degraders: effect of the type of blend and the addition of biosurfactants.
AB  - Biodegradation experiments for diesel/biodiesel blends in liquid cultures by
      petroleum degrading microbial consortium showed that for low amendments of
      biodiesel (10%) the overall biodegradation efficiency of the mixture after seven
      days was lower than for petroleum diesel fuel. Preferential usage of methyl
      esters in the broad biodiesel concentration range and diminished biodegradation
      of petroleum hydrocarbons for 10% biodiesel blend was confirmed. Rhamnolipids
      improved biodegradation efficiency only for blends with low content of biodiesel.
      Emulsion formation experiments showed that biodiesel amendments significantly
      affected dispersion of fuel mixtures in water. The presence of rhamnolipids
      biosurfactant affected stability of such emulsions and altered cell surface
      properties of tested consortium.

PMID- 18815028
TI  - Soda-anthraquinone pulping of palm oil empty fruit bunches and beating of the
      resulting pulp.
AB  - The influence of soda-anthraquinone pulping variables (temperature, time and soda
      concentration) and beating (number of PFI beating revolution) of palm oil empty
      fruit bunches (EFB) on the resulting paper sheets was studied, with a view to
      identifying the optimum operating conditions. Equations were derived that
      reproduced the properties of the paper sheets with errors less than 10-12% in 90
      95% of cases. An optimum compromise was found as regards operating conditions
      (15% soda, 170 degrees C, 70 min and 2400 number of PFI beating revolutions) that
      provided paper properties departing by less than 12% from their optimum values
      (59.63 Nm/g tensile index, 4.48% stretch, 4.17 kN/g burst index and 7.20 m
      Nm(2)/g tear index), and a beating grade of 47.5 degrees SR, acceptable to obtain
      paper sheets. Because these conditions involve a lower soda, temperature, time
      and beating than those required to maximize the studied paper properties, they
      can save chemical reagents, energy and immobilized capital for industrial
      facilities. On the other hand, the stretch properties of these pulp beaten are
      higher than those of others non-wood pulps, as wheat straw and olive wood.

PMID- 18815029
TI  - Synthesis of (3,4-dimethoxyphenoxy)alkylamino acetamides as orexin-2 receptor
      antagonists.
AB  - The discovery and synthesis of a series of (dimethoxyphenoxy)alkylamino
      acetamides as orexin-2 receptor antagonists from a small-molecule combinatorial
      library using a high-throughput calcium mobilization functional assay (HEK293
      human OX2-R cell line) is described. Active compounds show a good correlation
      between high-throughput single concentration screening data and measured IC(50)s.
      Specific examples exhibit IC(50) values of approximately 20 nM using human orexin
      A as the peptide agonist for the orexin-2 receptor.

PMID- 18815030
TI  - Pyrazolidine-3,5-dione derivatives as potent non-steroidal agonists of farnesoid
      X receptor: virtual screening, synthesis, and biological evaluation.
AB  - The identification of a novel pyrazolidine-3,5-dione based scaffold hit compound
      as Farnesoid X receptor (FXR) partial or full agonist has been accomplished by
      means of virtual screening techniques. A series of pyrazolidine-3,5-dione
      derivatives (1a-u and 7) was designed, synthesized, and evaluated by a cell-based
      luciferase transactivation assay for their agonistic activities against FXR. Most
      of them showed agonistic potencies and 10 of them (1a, 1b, 1d-f, 1j, 1n, 1t, 5b,
      and 7) exhibited lower EC(50) values than the reference drug CDCA. Molecular
      modeling studies for the representative compounds 1a, 1d, 1f, 1j, 1n, 1u, 5b, and
      7 were also presented. The novel structural scaffold has provided a new direction
      for finding potent and selective FXR partial and full agonists (referred to as
      'selective bile acid receptor modulators', SBARMs).

PMID- 18815031
TI  - Imidazoles: SAR and development of a potent class of cyclin-dependent kinase
      inhibitors.
AB  - An imidazole series of cyclin-dependent kinase (CDK) inhibitors has been
      developed. Protein inhibitor structure determination has provided an
      understanding of the emerging structure activity trends for the imidazole series.
      The introduction of a methyl sulfone at the aniline terminus led to a more orally
      bioavailable CDK inhibitor that was progressed into clinical development.

PMID- 18815032
TI  - Synthesis and evaluation of novel 4-amino-4,6-androstadiene-3,17-dione: an analog
      of formestane.
AB  - Synthesis of 4-amino-4,6-androstadiene-3,17-dione 7, an analog of formestane used
      in breast cancer therapy as an aromatase inhibitor, from 4-acetoxy-4-androstene
      3,17-dione 2 is described. This is the first report of a 4-amino diene (4,6)
      system in this series of molecules. The new (7) and reported molecules were
      screened by the National Cancer Institute (NCI, Bethesda, USA) for in vitro
      antitumor activity against 60 human cancer cell lines. Molecule 7 showed best
      activity against breast cancer cell line (MCF-7).

PMID- 18815033
TI  - Recent progress with FKBP-derived destabilizing domains.
AB  - The FKBP-derived destabilizing domains are increasingly being used to confer
      small molecule-dependent stability to many different proteins. The L106P domain
      confers instability to yellow fluorescent protein when it is fused to the N
      terminus, the C-terminus, or spliced into the middle of yellow fluorescent
      protein, however multiple copies of L106P do not confer greater instability.
      These engineered destabilizing domains are not dominant to endogenous degrons
      that regulate protein stability.

PMID- 18815034
TI  - Synthesis and antibacterial activity of 4''-O-heteroarylcarbamoyl derivatives of
      macrolide.
AB  - A series of novel 4''-position modified macrolide derivatives has been
      synthesized via a facile procedure. Their in vitro antibacterial activities
      against constitutively erythromycin-resistant strains were evaluated. Among the
      derivatives tested, compound 8a which has 11,12-carbamate and 4''-O
      heteroarylcarbamoyl groups was found to have potent activity against most
      resistant bacteria.

PMID- 18815035
TI  - Non-genomic effects of sex hormones on CLC-1 may contribute to gender differences
      in myotonia congenita.
AB  - Myotonia congenita is caused by mutations in the voltage-gated chloride channel
      ClC-1. It is more severe in men than women and often worsens during pregnancy,
      but the basis for these gender differences is not known. We show here that both
      testosterone and progesterone rapidly and reversibly inhibit wild-type ClC-1
      channels expressed in Xenopus oocytes by causing a prominent rightward shift in
      the voltage dependence of their open probability. In contrast, 17beta-estradiol
      at similar concentrations causes only a small shift. Progesterone and
      testosterone also profoundly inhibit ClC-1 channels containing the mutation F297S
      associated with dominantly inherited myotonia congenita. The effects of sex
      hormones are likely to be non-genomic because of their speed of onset and
      reversibility. These results suggest a possible mechanism to explain how the
      severity of myotonia congenita can be modulated by sex hormones.

PMID- 18815037
TI  - Sarcoidosis in a case of MuSK-positive myasthenia gravis.
AB  - Whereas the coexistence of different autoimmune or rheumatologic diseases with
      myasthenia gravis is well documented, the combination of myasthenia with
      sarcoidosis is extremely rare. There very few case reports of patients suffering
      from these two immune-mediated diseases. Nearly all had acetylcholine receptor
      antibodies. As far as we know myasthenia gravis with antibodies to muscle
      specific tyrosine kinase-MuSK--has not been associated with any form of
      sarcoidosis. We present probably the first case of MuSK-positive myasthenia
      gravis with concurrent, asymptomatic pulmonary sarcoidosis.

PMID- 18815038
TI  - Differential diagnosis of muscular hypotonia in infants: the kyphoscoliotic type
      of Ehlers-Danlos syndrome (EDS VI).

PMID- 18815039
TI  - Posture analysis on young women before and after 60 days of -6 degrees head down
      bed rest (Wise 2005).
AB  - Twenty-four women divided into three groups: control, exercise and nutrition,
      have been involved in a -6 degrees head down bed rest (HDBR) experiment for 60
      days. The objective was to analyse the effects of microgravity on balance
      function regulation. Group comparisons assessed the efficiency of countermeasures
      (specific exercises and in particular diet) on the deleterious effects of
      simulated microgravity. Measurements of orthostatic and dynamic balance were
      taken 9 and 2 days prior to the experiment, on the first day of getting up, the
      following day and 4 and 10 days after, under two visual conditions: eyes open and
      eyes closed. The results confirmed that, as in any other test performed with
      ordinary subjects, the postural balance performances are better with eyes open
      than with eyes closed. The static and dynamic postural performances were impaired
      on the first day of recovery (R0) following HDBR. This impairment lasted up to 4
      days after getting up and, afterwards the volunteers recovered their initial
      performances. The exercise group recovered static postural performances more
      quickly than the other groups whereas there were no differences in the recovery
      of the dynamic balance performances.

PMID- 18815040
TI  - Gaze stabilization and gait performance in vestibular dysfunction.
AB  - BACKGROUND: The gaze stability test (GST) quantifies the ability of a person to
      recognize a target projected on a personal computer monitor during active head
      movement. PURPOSE: The purpose of this study was to determine if there was a
      relationship between clinical measures of walking performance and the GST in
      patients with vestibular disorders and in healthy subjects. We hypothesized that
      impairment of the ability to keep objects in focus during active head movement
      would be correlated with walking performance. SUBJECTS: Twenty older asymptomatic
      adults acted as controls and 12 patients with either unilateral or bilateral
      vestibular disease participated. METHODS: The GST quantifies the maximum velocity
      that a person can move their head in the pitch and yaw planes while retaining the
      ability to read an optotype that is momentarily projected onto a computer screen.
      Subjects were scored while performing the Dynamic Gait Index (DGI) and the Timed
      "Up & Go" (TUG) tests. RESULTS: Walking performance on the DGI and TUG were
      significantly associated with GST results in subjects with vestibular disorders,
      but not in control subjects. Abnormalities of gait could be identified by GST
      cutoff values of 65 degrees s(-1) in the pitch plane and 63 degrees s(-1) in the
      yaw plane. DISCUSSION/CONCLUSION: In older subjects with vestibular disorders,
      gaze stability, as assessed by the GST, is associated with reduced test scores on
      measures of gait performance.

PMID- 18815041
TI  - Cluster analysis to classify gait alterations in rheumatoid arthritis using peak
      pressure curves.
AB  - OBJECTIVE: To detect gait alterations in rheumatoid arthritis (RA) patients using
      peak pressure curves (PPC) and normalized force curves (NFC) instead of clinical
      classification based on the health assessment questionnaire (HAQ). METHODS: Three
      RA groups--30 patients each--were classified according to their HAQ score.
      Cluster analysis based on a k-means algorithm was applied to PPCs and NFCs in
      order to classify RA patients with respect to amplitude and shapes of such gait
      parameters. RESULTS: The best gait pattern identification was obtained by
      clustering PPCs into three clusters. Peak pressures of the three identified
      patterns were 1169.5+/-99.4 kPa for cluster 1, 885.8+/-165.2 kPa for cluster 2
      and 402.0+/-128.5 kPa for cluster 3 (statistically different, Student's t-test,
      p<0.001). 41 patients were included in cluster 3, 31 in cluster 2 and only 18
      patients in cluster 1. Most RA3 patients--17 out of 30--showed low peak pressures
      and almost normal PPCs (cluster 3). Cluster 2, which incorporated altered PPCs,
      was mainly formed by RA1 and RA2 patients. CONCLUSIONS: PPC appears as a reliable
      gait parameter for a shape-based clustering algorithm. The proposed cluster
      analysis was proved to be reliable and the delivered classifications stable. The
      distribution of RA patients among the three identified PPC clusters showed only a
      partial agreement between clinical and functional classification, thus revealing
      the development of specific gait strategies related to the pathology more than to
      its clinical level of severity. This finding may be clinically relevant and
      support effective treatment of RA gait related pathologies.

PMID- 18815042
TI  - The use of rubber foam pads and "sensory ratios" to reduce variability in static
      posturography assessment.
AB  - Despite the numerous works published, static posturography has still a limited
      clinical use due to its intrinsic inter-individual high variability. For this
      reason, foam pads have been introduced but their use is still not standardized.
      Aim of the study was to define the variability of static posturography parameters
      in standard and foam standing. METHODS: 50 healthy subjects were studied with
      static posturography in four standing conditions: eyes open (EO) and eyes closed
      (EC), with and without foam pads. Unstable tests have been performed with two
      different types of rubber foam pads placed on the force platform. "Sensory
      ratios" have been calculated by the ratio of sway length among the four different
      conditions, adapted from dynamic posturography, in order to measure the relative
      contributions of vestibular, visual and somatosensory inputs. RESULTS: Static
      posturography in standard conditions showed unacceptable coefficients of
      variation (>than 15%) for all the parameters. The use of foam pads reduced the
      high intrinsic variability, in particular for LFS (12.6-15.4%). The use of
      "sensory ratios" led to decrease the inter-subject coefficient of variation of
      this measurement to about 9.47-14.42% using the bilayer foam pads. CONCLUSIONS:
      Further studies are needed to confirm these data by applying the ratio formulas
      in clinical practice.

PMID- 18815043
TI  - Recording scapular motion using an acromion marker cluster.
AB  - Disorders of the shoulder complex can be accompanied by changes in the movement
      pattern of the scapula. However, scapular motion is difficult to measure. A
      possible non-invasive method for dynamic three-dimensional kinematic measurement
      of the human scapula is the use of a marker cluster placed on the flat part of
      the acromion. A small light-weight acromion marker cluster (AMC) is presented in
      this study. In order to assess validity, kinematics obtained with the AMC were
      compared to simultaneous scapula locator (SL) recordings in a series of postures.
      The test/retest variability of replacement of the AMC, was also assessed.
      Measurement errors appeared to be sensitive for the plane of movement, the degree
      of humerus elevation, and replacement of the AMC. The AMC generally under
      estimated scapula motion, compared to the SL. Some significant differences were
      found between the two methods, although the absolute differences were small
      (maximum mean difference 8.4 degrees in extreme position). In humerus forward
      flexion and abduction the maximum mean differences were 6 degrees or lower. In
      conclusion, the AMC is a valid method of measuring scapular movement during arm
      elevation that could be used in shoulder pathologies. Placement and planes of
      movement should be carefully considered and elevation of the humerus should not
      exceed 100 degrees.

PMID- 18815044
TI  - Changes in axonal excitability and burst pattern behaviour in synkinesis.
AB  - Synkinesis after severe facial nerve paralysis has been related to the processes
      of aberrant reinnervation and increased excitability of the facial nucleus. We
      present the electrophysiological features of synkinesis in a 32-year-old woman
      who developed grouped 'myokymic-like' discharges with eye blinking in the absence
      of spontaneous muscle activity. With eye blinks, the interspike intervals of
      discharges in the orbicularis oris varied between 25-150Hz, overlapping with
      rates of myokymia and neuromyotonia. Analysis of the discharge patterns in the
      present case suggests that synkinesis reflects aberrant regeneration with effects
      mediated by properties of axonal excitability that determine the burst pattern
      characteristics.

PMID- 18815046
TI  - Prevalence of sporadic inclusion body myositis and factors contributing to
      delayed diagnosis.
AB  - The prevalence of sporadic inclusion body myositis (sIBM) is variable in
      different populations and ethnic groups. A previous survey in Western Australia
      in 2000 found a prevalence of 9.3 per million population. We have now performed a
      follow-up survey to determine whether there has since been any change in
      prevalence. The current prevalence was found to be 14.9 per million population,
      with a prevalence of 51.3 per million population in people over 50 years of age.
      This is the highest reported prevalence of sIBM and correlates with a high
      frequency of HLA-DR3 and the 8.1 major histocompatibility complex ancestral
      haplotype in this population. Review of a combined cohort of 57 sIBM cases from
      three Australian centres revealed a high rate of initial misdiagnosis and a mean
      time to diagnosis of 5.2 years, which suggests that even the latest prevalence
      figure may be an underestimate, and emphasising the need to increase the level of
      awareness of the condition among the medical community.

PMID- 18815045
TI  - Antidepressants modulate the in vitro inhibitory effects of propofol and ketamine
      on norepinephrine and serotonin transporter function.
AB  - Norepinephrine transporter (NET) and serotonin transporter (SERT) proteins
      regulate norepinephrine (NE) and serotonin via their reuptake function and are
      targets of antidepressants action. Several intravenous (IV) anesthetics have been
      shown to inhibit NET and SERT. The interactions between antidepressants and
      anesthetics on transporter function, however, are not well studied. We examined
      the effect of different IV anesthetics on NET and SERT function, with and without
      chronic antidepressant pretreatment, by measuring NE or 5-hydroxytryptamine (5
      HT) uptake and determined NET and SERT protein expression via immunoblotting.
      Both ketamine and propofol inhibited NET dose-dependently (propofol 10(-4)M 
      22%+/-5.6%, and propofol 10(-3)M -35%+/-5.7%; ketamine 10(-4)M -23%+/-4.1% and
      ketamine 10(-3)M -73%+/-2.9%); and SERT (propofol 10(-4)M -11%+/-4.3% and
      propofol 10(-3)M -23%+/-3.8%; ketamine 10(-4)M -29%+/-5.2% and ketamine 10(-3)M 
      63%+/-6.4%). Etomidate and thiopental had no effect on either NET or SERT
      function. Desipramine and fluoxetine, specific inhibitors of NET and SERT,
      respectively, both enhanced the inhibitory effects of propofol but reduced the
      inhibitory effects of ketamine on NET and SERT functions. IV anesthetics
      treatment did not change transporter protein expression in the presence of its
      respective inhibitor. Our results demonstrate that both ketamine and propofol
      inhibited SERT and NET function, but the inhibition was differentially modulated
      by antidepressants. Therefore, in the clinical context, this would suggest that
      patients receiving antidepressant treatments might have altered response to IV
      anesthetics in an agent-specific manner.

PMID- 18815047
TI  - Needle in the haystack: structure-based toxin discovery.
AB  - In the current data-rich era, making the leap from sequence data to knowledge is
      a task that requires an elegant bioinformatics toolset to pinpoint pressing
      research questions. Therefore, a strategy to expand important protein-family
      knowledge is required, particularly in cases in which primary sequence identity
      is low but structural conservation is high. For example, the mono-ADP
      ribosylating toxins fit these criteria and several approaches have been used to
      accelerate the discovery of new family members. The strategy evolved from
      conduction of PSI-BLAST searches through to the combination of secondary
      structure prediction with pattern-based searches. However, a newly developed
      tactic, in which fold recognition dominates, reduces reliance on sequence
      similarity and advances scientists toward a true structure-based protein-family
      expansion methodology.

PMID- 18815048
TI  - Knowledgebase for addiction-related genes: is it possible an extrapolation to
      rational multi-target drug design?
AB  - In recent years the single-probe-single-target approach in drug design has
      started to be smoothly replaced by the single-probe-multiple-target (or multi
      target) one, where a single drug is able to tackle different, but disease-related
      targets in a selective manner. However, the design of multi-target drugs has been
      hindered by a lack of a systematic network of disease-related common pathways.
      The recent development of the knowledgebase of addiction-related genes (KARG) has
      provided important hints on how to rationally design multi-target probes by
      connecting experimental techniques with available network models. In this
      perspective, the use of KARG as a template to build knowledgebases of disease
      related genes for the rational multi-target drug design is suggested. Moreover,
      it is proposed that building knowledgebases of disease-related genes will become
      a necessary and ubiquitous tool in the rational design of multi-target drugs.

PMID- 18815049
TI  - Synthesis and biological evaluation of immunosuppressive agent DZ2002 and its
      stereoisomers.
AB  - DZ2002 and its related stereoisomers were efficiently synthesized. The optical
      data of (R)- and (S)-DZ2002 were disclosed here for the first time. Their
      inhibitory potency was evaluated on SAHase and MLR assay in the mean time. In
      accordance with respective inhibitory potency of SAHase, the immunosuppressive
      potency order was demonstrated as (S)-DZ2002>(Rac)-DZ2002>(R)-DZ2002>(Keto)
      DZ2002. These results indicate (S)-configuration of 2-chiral center in DZ2002 is
      important for binding with SAHase.

PMID- 18815050
TI  - 4-Anilino-7-alkenylquinoline-3-carbonitriles as potent MEK1 kinase inhibitors.
AB  - A series of substituted 7-alkenyl 4[3-chloro-4-(1-methyl-1H-imidazol-2
      ylsulfanyl)]anilino-3-quinolinecarbonitrile analogs were synthesized and
      evaluated as MEK1 kinase inhibitors. The synthetic details, structure-activity
      relationships, biological activity, and selected oral exposure studies of these
      analogs are described. From these studies, compound 5m was chosen as a strong
      candidate for further evaluation. The selectivity of 5m was ascertained against a
      panel of 17 kinases, where activity was observed against EGFR, Src, Lyn, and IR
      kinases. Western blot studies in WM-266 cells demonstrated that 5m inhibited
      phosphorylation of ERK, while additional kinase pathways tested showed no
      inhibition at up to 10 microM of 5 m. PK studies, as well as a xenograft and in
      vivo biomarker studies are described for 5m.

PMID- 18815051
TI  - Bisphosphonated fluoroquinolone esters as osteotropic prodrugs for the prevention
      of osteomyelitis.
AB  - Osteomyelitis is a difficult to treat bacterial infection of the bone. Delivering
      antibacterial agents to the bone may overcome the difficulties in treating this
      illness by effectively concentrating the antibiotic at the site of infection and
      by limiting the toxicity that may result from systemic exposure to the large
      doses conventionally used. Using bisphosphonates as osteophilic functional
      groups, different forms of fluoroquinolone esters were synthesized and evaluated
      for their ability to bind bone and to release the parent antibacterial agent.
      Bisphosphonated glycolamide fluoroquinolone esters were found to present a
      profile consistent with effective and rapid bone binding and efficient release of
      the active drug moiety. They were assessed for their ability to prevent bone
      infection in vivo and were found to be effective when the free fluoroquinolones
      were not.

PMID- 18815052
TI  - Computational structure-activity relationship analysis of non-peptide inducers of
      macrophage tumor necrosis factor-alpha production.
AB  - Previously, we screened a series of arylcarboxylic acid hydrazide derivatives for
      their ability to induce macrophage tumor necrosis factor alpha (TNF-alpha)
      production and identified 16 such compounds. In the present study, we evaluated
      23 additional arylcarboxylic acid hydrazides and found that seven of these
      compounds also induced macrophage TNF-alpha production, representing novel
      compounds with this activity. The total set of active compounds was then used for
      computational structure-activity relationship (SAR) analysis to further optimize
      lead molecules. A sequence of (1) linear discriminant analysis, (2)
      classification tree analysis with linear combination, and (3) univariate splits
      based on atom pair descriptors led to the derivation of SAR rule-based algorithms
      with fitting accuracy of 96.5%, 91.9%, and 84.9%, respectively. The SAR rules
      obtained from classification tree analysis with univariate splits, which was
      based on three atom pair descriptors only, revealed that the main factors
      influencing agonist activity of arylcarboxylic acid hydrazide derivatives were
      the presence of a methyl or trifluoromethyl group in the benzene ring attached to
      the furan moiety, an alkoxy group in the aromatic ring near the
      methylenehydrazide linker, and two or more halogen atoms (chlorine or bromine) on
      one side of the dumbbell-shaped hydrazide molecule opposed by an aromatic moiety
      on the opposite side of the molecule. Thus, these rules represent a relatively
      simple classification approach for de novo design of small-molecule inducers of
      macrophage TNF-alpha production.

PMID- 18815053
TI  - Accuracy and repeatability of cone-beam computed tomography (CBCT) measurements
      used in the determination of facial indices in the laboratory setup.
AB  - AIM: To assess the three dimensional (3D) surface accuracy of a phantom's face
      acquired from a cone-beam computed tomography (CBCT) scan and to determine the
      reliability of selected cephalometric measurements performed with Maxilim
      software (Medicim N.V., Mechelen, Belgium). MATERIAL AND METHODS: A mannequin
      head was imaged with a CBCT (I-CAT, Imaging Sciences International, Inc.,
      Hatfield, USA). The data were used to produce 3D surface meshes (Maxilim and
      Mimics, Materialise N.V., Leuven, Belgium) which were compared with an optical
      surface scan of the head using Focus Inspection software (Metris N.V., Leuven,
      Belgium). The intra- and inter-observer reliability for the measurement of
      distances between facial landmarks with Maxilim 3D cephalometry were determined
      by calculating Pearson correlation coefficients and intraclass correlation (ICC).
      The Dahlberg formula was used to assess the method error (ME). RESULTS: (1) The
      maximal range of the 3D mesh deviations was 1.9 mm for Maxilim, and 1.8mm for
      Mimics segmentation. (2) Test-retest and inter-observer reliability were high;
      Pearson's correlation coefficient was 1.000 and the ICC was 0.9998. The ME of the
      vertical measurements was a little larger than that calculated for the width
      measurements. Maximum ME was 1.33 mm. CONCLUSIONS: The 3D surface accuracy of
      CBCT scans segmented with Maxilim and Mimics software is high. Maxilim also shows
      satisfactory intra- and inter-assessor reliability for measurement of distances
      on a rigid facial surface.

PMID- 18815054
TI  - The therapeutic effect of TNFR1-selective antagonistic mutant TNF-alpha in murine
      hepatitis models.
AB  - Tumor necrosis factor-alpha (TNF-alpha) is critically involved in a wide variety
      of inflammatory pathologies, such as hepatitis, via the TNF receptor-1 (TNFR1).
      To develop TNFR1-targeted anti-inflammatory drugs, we have already succeeded in
      creating a TNFR1-selective antagonistic mutant TNF-alpha (R1antTNF) and shown
      that R1antTNF efficiently inhibits TNF-alpha/TNFR1-mediated biological activity
      in vitro. In this study, we examined the therapeutic effect of R1antTNF in acute
      hepatitis using two independent experimental models, induced by carbon
      tetrachloride (CCl(4)) or concanavalin A (ConA). In a CCl(4)-induced model,
      treatment with R1antTNF significantly inhibited elevation in the serum level of
      ALT (alanine aminotransferase), a marker for liver damage. In a ConA-induced T
      cell-mediated hepatitis model, R1antTNF also inhibited the production of serum
      immune activated markers such as IL-2 and IL-6. These R1antTNF-mediated
      therapeutic effects were as good as or better than those obtained using
      conventional anti-TNF-alpha antibody therapy. Our results suggest that R1antTNF
      may be a clinically useful TNF-alpha antagonist in hepatitis.

PMID- 18815055
TI  - Positioning epidemiology in a changing environment over the next 25 years:
      introduction.

PMID- 18815056
TI  - Touchant-touche: the role of self-touch in the representation of body structure.
AB  - The "body image" is a putative mental representation of one's own body, including
      structural and geometric details, as well as the more familiar visual and
      affective aspects. Very little research has investigated how we learn the
      structure of our own body, with most researchers emphasising the canonical visual
      representation of the body when we look at ourselves in a mirror. Here, we used
      non-visual self-touch in healthy participants to investigate the possibility that
      primary sensorimotor experience may influence cognitive representations of one's
      own body structure. Participants used the fingers of one hand (the 'active'
      hand), to touch the fingers of the other (the 'passive' hand). A conflict between
      the experience of the active and passive hand was introduced by experimenter
      interleaving their fingers with the fingers of the participant's passive hand.
      This led to the active hand experiencing that it touched more fingers than the
      passive hand felt it was being touched by. The effects on representation of body
      structure were assessed using an implicit measure based on Kinsbourne and
      Warrington's 'in-between task'. We found an underestimation of the number of
      fingers in the central part of the hand specifically linked to the experience of
      self-touch. This pattern of results corresponds to the experience of the passive
      hand, but not the active hand. Nevertheless, comparable reorganisation of fingers
      within the hand representation was found for both active and passive hands. We
      show that primary sensorimotor experience can modify the representation of body
      structure. This modification is driven by the passive experience of being
      touched, rather than by the active experience of touching. We believe this is the
      first experimental study of effects of self-touch on the mental representation of
      the body.

PMID- 18815058
TI  - The GALA Trial--a summary of the findings.

PMID- 18815059
TI  - High performance liquid chromatography determination of cytochrome P450 1A and 2C
      activities in bovine liver microsomes.
AB  - This study reports fluorescence high performance liquid chromatography (HPLC) and
      UV-Vis HPLC methods for the determination of 7-ethoxyresorufin O-deethylase
      (EROD) and tolbutamide methylhydroxylase (TMH) activities, respectively, using
      bovine liver microsomes. The detection limits were 0.022 and 5.5 pmol on the
      column, respectively; intra-day and inter-day precisions (expressed as relative
      standard deviation) were <10%. Both methods showed enough sensitivity to allow
      for an accurate determination of enzyme kinetic parameters according to Michaelis
      Menten plots and the results were: K(m)=0.23+/-0.051 microM, V(max)=0.488+/-0.035
      nmol/min/mg protein for EROD activity, and K(m)=1010+/-155.7 microM,
      V(max)=0.089+/-0.006 nmol/min/mg protein for TMH activity. An Eadie-Hofstee plot
      analysis showed that in bovine liver microsomes, EROD and TMH activities followed
      a monophasic kinetic pattern. alpha-Naphthoflavone, a cytochrome P450 1A1/2
      (CYP1A1/2) inhibitor, and sulfaphenazole, a cytochrome P450 2C9 (CYP2C9)
      inhibitor, decreased EROD and TMH activities, respectively. The sensitivity of
      the methods allowed the use of microsomes with low enzyme activity, such as those
      from veal calf liver. Thus, EROD and TMH activities may be adopted as markers for
      the evaluation of CYP1A and CYP2C9-like activities in liver microsomes from veal
      and beef cattle.

PMID- 18815060
TI  - Solid state water motions revealed by deuterium relaxation in 2H2O-synthesized
      kanemite and 2H2O-hydrated Na+-zeolite A.
AB  - Deuterium NMR relaxation experiments, low temperature deuterium NMR lineshape
      analysis, and FTIR spectra are consistent with a new model for solid state jump
      dynamics of water in (2)H(2)O-synthesized kanemite and (2)H(2)O-hydrated Na(+)
      Zeolite A. Exchange occurs between two populations of water: one in which water
      molecules are directly coordinated to sodium ions and experience C(2) symmetry
      jumps of their OH bonds, and a population of interstitial water molecules outside
      the sodium ion coordination sphere that experience tetrahedral jumps of their OH
      bonds. For both samples the C(2) jump rate is much faster than the tetrahedral
      jump rate. (2)H NMR relaxation experiments match well with the fast exchange
      regime of the model over a wide range of temperatures, including room temperature
      and above. For hydrated Zeolite A, the kinetic activation parameters for the
      tetrahedral and C(2) symmetry jumps are Delta H tet++=+17 kJ/mol, Delta S tet++=
      109 J/(mol K), Delta H C2++=+19 kJ/mol, and Delta S C2++=-20 J/(mol K). For
      kanemite, Delta H tet++ =+23 kJ/mol, Delta S tet++=-69 J/(mol K), Delta H C2++
      =+23 kJ/mol, and Delta S C2++ =-11 J/(mol K).

PMID- 18815061
TI  - New ceramic EPR resonators with high dielectric permittivity.
AB  - New EPR resonators were developed by using a ceramic material with a high
      dielectric constant, epsilon=160. The resonators have a high quality factor,
      Q=10(3), and enhance the sensitivity of an EPR spectrometer up to 170 times. Some
      advantages of the new ceramic resonators are: (1) cheaper synthesis and
      simplified fabricating technology; (2) wider temperature range; and (3) ease of
      use. The ceramic material is produced with a titanate of complex oxides of rare
      earth and alkaline metals, and has a perovskite type structure. The resonators
      were tested with X-band EPR spectrometers with cylindrical (TE(011)) and
      rectangular (TE(102)) cavities at 300 and 77K. We discovered that EPR signal
      strength enhancement depends on the dielectric constant of the material,
      resonator geometry and the size of the sample. Also, an unusual resonant mode was
      found in the dielectric resonator-metallic cavity structure. In this mode, the
      directions of microwave magnetic fields of the coupled resonators are opposite
      and the resonant frequency of the structure is higher than the frequency of empty
      metallic cavity.

PMID- 18815063
TI  - Genetic variation may influence obesity only under conditions of diet: analysis
      of three candidate genes.
AB  - Under the hypothesis of obesity as a polygenetic disease numerous genes have been
      associated with an obese phenotype and metabolic co-morbidities. The cannabinoid
      receptor 1 (CB 1) is part of an underinvestigated system that participates in
      appetite control. Previous publications suggest that the endocannabinoid systems
      interact with the better understood leptin-melanocortin axis. Neuropeptide Y
      (NPY) is a player in the latter. Finally resistin has been shown to influence NPY
      expression in the brain. In a cohort of 1721 caucasion men and women with a BMI
      of 25kg/m(2) or more we therefore investigated three candidate polymorphisms at
      baseline and following 3 months low fat caloric restriction diet by polymerase
      chain reaction and restriction digestion: the 1359 G/A variant of the cannabinoid
      receptor 1 (CB1), the L7P variation in neuropeptide Y (NPY) and the -420C>G
      polymorphism in resistin. Comparing groups according to genotype for each gene
      separately revealed significant results at baseline only for the CB1 gene.
      However, upon dieting significant data was found for all 3 genes. Carriers of at
      least one A allele in CB1 lost more weight and reduced LDL cholesterol more than
      wildtype patients. LL homocygotes in NPY had a greater reduction in glucose,
      triglycerides, and LDL cholesterol whereas in resistin carriers of the G allele
      had a greater reduction in weight and triglycerides. Creating two groups defined
      by NPY and resistin genotype, respectively, with similar BMI values resulted in
      significant differences concerning weight loss and metabolic improvement. In
      conclusion, genetic polymorphisms associated with obesity may become relevant
      only under the condition of a low calory diet. The presence of a certain genotype
      may then be beneficial for obesity treatment.

PMID- 18815062
TI  - Characterization of common SMPD1 mutations causing types A and B Niemann-Pick
      disease and generation of mutation-specific mouse models.
AB  - Herein we describe detailed characterization of four common mutations (L302P,
      H421Y, R496L and DeltaR608) within the acid sphingomyelinase (ASM) gene causing
      types A and B Niemann-Pick disease (NPD). In vitro and in situ enzyme assays
      revealed marked deficiencies of ASM activity in NPD cell lines homoallelic for
      each mutation, although Western blotting and fluorescent microscopy showed that
      the mutant ASM polypeptides were expressed at normal levels and trafficked to
      lysosomes. Co-immunoprecipitation of the polypeptides with the ER chaperone, BiP,
      confirmed these findings, as did in vitro expression of the mutant cDNAs in
      reticulocyte lysates. We further developed a computer assisted, three-dimensional
      model of human ASM based on homologies to known proteins, and used this model to
      map each NPD mutation in relation to putative substrate binding, hydrolysis and
      zinc-binding domains. Lastly, we generated transgenic mice expressing the R496L
      and DeltaR608 mutations on the complete ASM knock-out background (ASMKO), and
      established breeding colonies for the future evaluation of enzyme enhancement
      therapies. Analysis of these mice demonstrated that the mutant ASM transgenes
      were expressed at high levels in the brain, and in the case of the DeltaR608
      mutation, produced residual ASM activity that was significantly above the ASMKO
      background.

PMID- 18815064
TI  - A case of Staphylococcus saccharolyticus pneumonia.
AB  - This paper reports a case of a very rare and dangerous disease, Staphylococcus
      saccharolyticus pneumonia. In this tragic case, a 21-year-old patient died after
      he did not receive timely diagnosis and proper treatment.

PMID- 18815065
TI  - [Hands and feet of prosimians primates. Attempts of morphologic
      characterization].
AB  - The length of the carpus and tarsus, the metacarpus and metatarsus, the fingers
      and toes of 142 prosimian apes was measured. The relationship expressed as a
      percentage was drawn up for each individual between the length of each osseous
      part and that of its third metacarpal in order to eliminate the differences
      related to the size of the rest of the body. This ratio was compared with that of
      man. The characteristic variations appeared at the level of the subfamilies.
      CONCERNING THE HAND: The carpus presented the same values as that of man except
      for that of the indris, which was shorter. The thumb had proportionally the same
      length as that of man, sometimes longer and sometimes smaller as in the Eulemurs,
      Hapalidea, Megalapidea, Indrises, Daubentonia and Perodictus. The different
      metacarpals, including the fourth, were a little shorter than the third. In these
      subfamilies, the second ray was also often shorter and even much shorter in the
      Megalapidea and the Perodictus. The other rays were a little longer, in
      particular the fourth which could exceed the third in rather many subfamilies.
      CONCERNING THE FOOT: The length of the tarsus was extremely variable. It was
      twice larger in the Galagoidae, definitely larger in the tarsius and discreetly
      in the Hapalidae, a little smaller in the other Lemurs and much smaller in the
      other Prosimian apes, joining in that the near totality of the simians. The
      hallux was proportionally as long as that of man and sometimes even longer. The
      metatarsals were sometimes a little longer, sometimes less long, but always
      appreciably of the same length between them. The other toes were short at the aye
      aye (daubentonia), of which the foot appeared even smaller than that of man. The
      toes of the other prosimious resembled much to the fingers and in the propithecus
      and the perodictus, the fourth took gigantic proportions. There has been
      establishment of an anatomical relation and functional calculus between the
      length of the last three rays of the hands and the feet of prosimian apes and the
      biomechanics of their trapezometacarpal and their first cuneometacarpal joints.

PMID- 18815066
TI  - Interleukin 23: a key cytokine in chronic inflammatory disease.

PMID- 18815067
TI  - [Turner's syndrome and procreation. Ovarian function and Turner's syndrome].
AB  - Ovarian failure is a typical feature in Turner's syndrome. The majority of
      follicles disappears prematurely after a normal determination of the ovary. This
      results from an accelerated loss of oocytes from the ovaries after the 18th week
      of fetal life or over a few postnatal years, usually before the onset of puberty.
      The cause and mechanism of this loss are unknown. X chromosomal anomaly due to
      deletions or haploinsufficiency of genes can explain the various degrees of
      ovarian failure. Spontaneous puberty occurs in 20-30% of Turner syndrome patients
      and their fertility rates vary from 5 to 10%. This indicates the possible
      presence and maturation of follicles in their ovaries in adolescence. In ovarian
      failure, the hormone replacement therapy (HRT) is necessary to achieve the
      development of normal female sexual characteristics, the self image or social
      functioning and to prevent osteoporosis. Pregnancy is now possible with oocyte
      donation. A careful cardiovascular follow-up is necessary. Cryoconservation
      represents one way for preserving the future fertility, but the optimal age of
      ovarian biopsy has to be studied.

PMID- 18815068
TI  - The importance of organ geometry and boundary constraints for planning of medical
      interventions.
AB  - Realistic modeling of medical interventions involving tool-tissue interactions
      has been considered to be a key requirement in the development of high-fidelity
      simulators and planners. Organ geometry, soft-tissue constitutive laws, and
      boundary conditions imposed by the connective tissues surrounding the organ are
      some of the factors that govern the accuracy of medical intervention planning. In
      this study it is demonstrated that, for needle path planning, the organ geometry
      and boundary constraints surrounding the organ are the most important factors
      influencing the deformation. As an example, the procedure of needle insertion
      into the prostate (e.g. for biopsy or brachytherapy) is considered. Image
      segmentation is used to extract the anatomical details from magnetic resonance
      images, while object-oriented finite element analysis (OOF) software is used to
      generate finite element (FE) meshes from the segmented images. Two-dimensional FE
      simulations that account for complex anatomical details along with relative
      motion between the prostate and its surrounding structure using cohesive zone
      models are compared with traditional simulation models having simple organ
      geometry and boundary constraints. Nodal displacements for these simpler models
      were observed to be up to 14 times larger than those obtained from the
      anatomically accurate models.

PMID- 18815069
TI  - Left ventricular solid body rotation in non-compaction cardiomyopathy: a
      potential new objective and quantitative functional diagnostic criterion?
AB  - BACKGROUND: Left ventricular (LV) twist originates from the interaction between
      myocardial fibre helices that are formed during the formation of compact
      myocardium in the final stages of the development of myocardial architecture.
      Since non-compaction cardiomyopathy (NCCM) is probably caused by intrauterine
      arrest of this final stage, it may be anticipated that LV twist characteristics
      are altered in NCCM patients, beyond that seen in patients with impaired LV
      function and normal compaction. AIMS: The purpose of this study was to assess LV
      twist characteristics in NCCM patients compared to patients with non-ischaemic
      dilated cardiomyopathy (DCM) and normal subjects. METHODS AND RESULTS: The study
      population consisted of 10 patients with NCCM, 10 patients with DCM, and 10
      healthy controls. LV twist was determined by speckle tracking echocardiography.
      In all controls and DCM patients, rotation was clockwise at the basal level and
      counterclockwise at the apical level. In contrast, in all NCCM patients the LV
      base and apex rotated in the same direction. CONCLUSIONS: These findings suggest
      that 'LV solid body rotation', with near absent LV twist, may be a new sensitive
      and specific, objective and quantitative, functional diagnostic criterion for
      NCCM.

PMID- 18815070
TI  - Telomere biology in heart failure.
AB  - The incidence and prevalence of cardiovascular disease increases progressively
      with advancing age. Cardiovascular disease is a major cause of morbidity and
      mortality in Western Countries. In the near future, as the population ages, it is
      expected that the population prevalence of cardiovascular disease will increase
      dramatically, imposing a major social and economical burden on society. Not only
      is age closely related to the development and progression of cardiovascular
      disease, but genetic and environmental factors also play an important role.
      Recently, a chromosomal mechanism, telomere shortening, has been considered a
      driving force by which genetic and environmental factors jointly affect
      biological aging, and possibly the risk for developing age-associated diseases.
      Telomeres are the extreme ends of chromosomes and shorten progressively during
      every cell cycle and therefore can be considered an indicator of biological age.
      In heart failure, telomere length is severely reduced. In the current review, we
      will discuss the emerging role of telomere biology in the pathophysiology of
      heart failure.

PMID- 18815072
TI  - Finding rule groups to classify high dimensional gene expression datasets.
AB  - Microarray data provides quantitative information about the transcription profile
      of cells. To analyze microarray datasets, methodology of machine learning has
      increasingly attracted bioinformatics researchers. Some approaches of machine
      learning are widely used to classify and mine biological datasets. However, many
      gene expression datasets are extremely high dimensionality, traditional machine
      learning methods cannot be applied effectively and efficiently. This paper
      proposes a robust algorithm to find out rule groups to classify gene expression
      datasets. Unlike the most classification algorithms, which select dimensions
      (genes) heuristically to form rules groups to identify classes such as cancerous
      and normal tissues, our algorithm guarantees finding out best-k dimensions
      (genes) to form rule groups for the classification of expression datasets. Our
      experiments show that the rule groups obtained by our algorithm have higher
      accuracy than that of other classification approaches.

PMID- 18815071
TI  - Cigarette smoke-induced left ventricular remodelling is associated with
      activation of mitogen-activated protein kinases.
AB  - AIM: To determine the effects of cigarette smoke (CS) exposure on the
      expression/activation of mitogen-activated protein kinases (MAPKs) (extracellular
      signal-regulated kinase [ERK1/2], p38-kinase [p38] and c-Jun NH2-terminal protein
      kinase [JNK]), norepinephrine (NE) levels and myocardial structure and function.
      METHODS: Rats were randomised to two groups: CS-exposed (n=12) or room air (CON)
      (n=10). After 5 weeks, the animals underwent echocardiography with pulse-wave
      Doppler flow measurements. Hearts were removed for microscopy and Western blot
      analysis. RESULTS: CS exposure was associated with significant increases in NE
      urinary levels and larger ventricular dimensions (mm) (CON=left ventricular end
      diastolic dimension [LVEDD] 7.99+/-0.10, LV end systolic dimension [LVESD] 4.55+/
      0.20, CS=LVEDD 8.3+/-0.10, LVESD 5.3+/-0.09, p=0.026, p=0.003). There was also
      evidence of systolic dysfunction in the CS-exposed group compared to the CON
      group (fractional shortening %, CON=43+/-2, CS=36+/-.09, p=0.010). In CS-exposed
      hearts, significant increases in phosphorylated p38/total p38 (0.975+/-0.05) and
      phosphorylated ERK1/2/totalERK1/2 (1.919+/-0.050) were found compared to CON
      hearts (0.464+/-0.008, 0.459+/-0.050, respectively). No significant differences
      were found in JNK levels between the groups. CONCLUSIONS: Increased NE levels and
      MAPK activation are associated with CS-related left ventricular remodelling.

PMID- 18815073
TI  - Genomic splice site prediction algorithm based on nucleotide sequence pattern for
      RNA viruses.
AB  - Splice site prediction on an RNA virus has two potential difficulties seriously
      degrading the performance of most conventional splice site predictors. One is a
      limited number of strains available for a virus species and the other is the
      diversified sequence patterns around the splice sites caused by the high mutation
      frequency. To overcome these two difficulties, a new algorithm called Genomic
      Splice Site Prediction (GSSP) algorithm, was proposed for splice site prediction
      of RNA viruses. The key idea of the GSSP algorithm was to characterize the
      interdependency among the nucleotides and base positions based on the eigen
      patterns. Identified by a sequence pattern mining technique, each eigen-pattern
      specified a unique composition of the base positions and the nucleotides
      occurring at the positions. To remedy the problem of insufficient training data
      due to the limited number of strains for an RNA virus, a cross-species strategy
      was employed in this study. The GSSP algorithm was shown to be effective and
      superior to two conventional methods in predicting the splice sites of five RNA
      species in the Orthomyxoviruses family. The sensitivity and specificity achieved
      by the GSSP algorithm was higher than 99 and 94%, respectively, for the donor
      sites, and was higher than 96 and 92%, respectively, for the acceptor sites.
      Supplementary data associated with this work are freely available for academic
      use at http://homepage.ntu.edu.tw/ approximately d91548013/.

PMID- 18815074
TI  - Diagnosis and management of placenta accreta.
AB  - The diagnosis of placenta accreta begins with clinical suspicion in patients at
      risk. Ultrasound and Doppler are first-choice diagnostic methods because of their
      accessibility and high sensitivity. Placental MRI is an accurate method of
      topographic stratification that makes it possible to define anatomy, to plan the
      surgical approach and to consider other therapeutic possibilities. Management of
      placenta percreta involves great technical dexterity and significant clinical
      support. The main challenges include controlling the haemorrhage and dissection
      of the invaded tissues. Nowadays, there are two treatment options: caesarean
      hysterectomy or a conservative approach. With the latter, there is a choice
      between leaving the placenta in situ and waiting for its later resolution, and a
      one-step surgery that addresses the problems of invasion, vascular control and
      myometrial damage in a single surgical act.

PMID- 18815075
TI  - Anti-inflammatory effect of miglustat in bronchial epithelial cells.
AB  - The role of CFTR deficiency in promoting inflammation remains unclear. Perez et
      al. [A. Perez, A.C. Issler, C.U. Cotton, T.J. Kelley, A.S. Verkman and P.B.
      Davis, CFTR inhibition mimics the cystic fibrosis inflammatory profile. Am J
      Physiol Lung Cell Mol Physiol 2007; 292:L383-L395.] recently demonstrated that
      the inhibition of function of w/t CFTR produces an inflammatory profile that
      resembles that observed in CF patients, whereas we found that correction of
      F508del-CFTR function with MPB-07 down-modulates the inflammatory response to P.
      aeruginosa in CF bronchial cells [M.C. Dechecchi, E. Nicolis, V. Bezzerri, A.
      Vella, M. Colombatti, B.M. Assael, et al., MPB-07 reduces the inflammatory
      response to Pseudomonas aeruginosa in cystic fibrosis bronchial cells. Am J
      Respir Cell Mol Biol 2007; 36, 615-624.]. Since both evidence support a link
      between CFTR function and inflammation, we extended our investigation to other
      F508del-CFTR correctors, such as miglustat (Norez, 2006), an approved drug for
      Gaucher disease, in comparison with the galactose analogue NB-DGJ. We report here
      that miglustat but not NB-DGJ restores F508del-CFTR function in CF bronchial
      epithelial IB3-1 and CuFi-1 cells. Miglustat and NB-DGJ reduce the inflammatory
      response to P. aeruginosa in both CF and non-CF bronchial cells, indicating that
      the anti-inflammatory effect is independent of the correction of F508del-CFTR
      function. Miglustat also inhibits the inflammatory response induced by the
      supernatant of mucopurulent material obtained from the lower airway tract of
      cystic fibrosis patients with chronic bacterial colonization (Ribeiro, 2005).
      Both compounds do not interfere with the adherence of P. aeruginosa to the cells
      and reduce the expression of IL-8 not only after challenge with P. aeruginosa but
      also after exposure to TNF alpha or IL-1 beta, suggesting an effect on
      transduction proteins downstream and in common with different receptors for
      pathogens. Finally, miglustat has no major effects on overall binding activity of
      transcription factors NF-kappaBNF-kB and AP-1. Since miglustat is an approved
      drug, it could be investigated as a novel anti-inflammatory molecule to
      ameliorate lung inflammation in CF patients.

PMID- 18815076
TI  - Direct and indirect separations of five isomers of Brivanib Alaninate using
      chiral high-performance liquid chromatography.
AB  - Brivanib Alaninate is a novel chiral prodrug possessing two stereogenic centers.
      Simultaneous HPLC separation of five isomers of Brivanib Alaninate was
      systematically investigated on a wide variety of polysaccharide-based chiral
      stationary phases (CSPs) using underivatization and pre-column derivatization
      methods. The influence of derivatizing groups and mobile phase composition on the
      enantioseparation and retention behavior of Brivanib Alaninate compounds was
      studied. To better understand the chiral recognition mechanism, the temperature
      effect was also evaluated. The results of these studies led to the first complete
      HPLC resolution of all five isomers of Brivanib Alaninate as carbobenzyloxy (CBZ)
      derivatives on a cellulose benzoate CSP (OJ-H).

PMID- 18815077
TI  - Arginine and methylated arginines in human plasma and urine measured by tandem
      mass spectrometry without the need for chromatography or sample derivatisation.
AB  - A method for the simultaneous analysis of asymmetric dimethylarginine, symmetric
      dimethylarginine, monomethylarginine and arginine in human plasma and urine, with
      short analysis time and isotopic internal standardisation for each analyte is
      described. The method requires neither sample derivatisation nor the need for
      chromatographic separation of analytes. The method described shows good precision
      and accuracy and is suited for both research purposes and implementation in the
      busy, routine clinical laboratory. In addition the synthesis and utilisation of
      isotopically labelled symmetric dimethylarginine and monomethylarginine is
      described for the first time, avoiding the use of surrogates such as homoarginine
      for internal standardisation.

PMID- 18815078
TI  - Single step purification of plasmid DNA using peptide ligand affinity
      chromatography.
AB  - Single step affinity chromatography was employed for the purification of plasmid
      DNA (pDNA), thus eliminating several steps compared with current commercial
      purification methods for pDNA. Significant reduction in pDNA production time and
      cost was obtained. This chromatographic operation employed a peptide-monolith
      construct to isolate pDNA from Escherichia coli (E. coli) impurities present in a
      clarified lysate feedstock. Mild conditions were applied to avoid any degradation
      of pDNA. The effect of some important parameters on pDNA yield was also evaluated
      with the aim of optimising the affinity purification of pDNA. The results
      demonstrate that 81% of pDNA was recovered and contaminating gDNA, RNA and
      protein were removed below detectable levels.

PMID- 18815079
TI  - Solvent-enhanced microwave-assisted derivatization following solid-phase
      extraction combined with gas chromatography-mass spectrometry for determination
      of amphetamines in urine.
AB  - An approach using microwave-assisted derivatization (MAD) following solid-phase
      extraction (SPE) combined with gas chromatography-mass spectrometry (GC-MS) was
      developed to determine amphetamines in urine samples. The parameters affecting
      the derivatization efficiency - including microwave power and irradiation time -
      were investigated. Besides, solvent is thought critically important to MAD.
      Derivatization performance was studied using various solvents and compared with
      the performance obtained without solvent. Derivatization efficiency was clearly
      found to be enhanced by the presence of solvent. The highest derivatization
      efficiencies were obtained in ethyl acetate (EA) under microwave power of 250W
      for 1min. Calibration curves for all amphetamines were linear over a range from 1
      to 1000ng/mL, with correlation coefficients above 0.9992. The intra-day and inter
      day precision were less than 15%. The applicability of the method was tested by
      analyzing amphetamine-abusing subjects urine samples. Accordingly, the solvent
      enhanced MAD-GC-MS method appears to be adequate for determining amphetamines in
      urine.

PMID- 18815080
TI  - Development and validation of a LC/MS/MS method for quantifying the next
      generation calcineurin inhibitor, voclosporin, in human whole blood.
AB  - A rapid, accurate, and reproducible liquid chromatography electrospray tandem
      mass spectrometry (LC/ESI-MS/MS) method was developed and validated for the
      therapeutic drug monitoring of voclosporin in human whole blood. Sample aliquots
      of 100muL were processed utilizing a protein precipitation procedure that
      contained a mixture of methanol, 0.2M ZnSO(4), and deuterated voclosporin
      internal standard. Supernatant was injected onto a Zorbax SB-C8, 2.1x12.5mm
      column (at 60 degrees C), and washed with water-acetonitrile, supplemented with
      0.02% glacial acetic acid and 0.02mM sodium acetate, to remove poorly retained
      components. After washing, water-MeOH (with 0.02% glacial acetic acid and 0.02mM
      sodium acetate) was used to elute the voclosporin and internal standard to the
      Applied Biosystems/MDS-Sciex API3000 mass spectrometer for detection in multiple
      reaction monitoring. Analytical performance was assessed in the range of 1
      200ng/ml in whole blood. This method has been used to quantify concentrations of
      voclosporin in whole blood from healthy volunteers participating in a
      pharmacokinetic study.

PMID- 18815081
TI  - Nanocomposite hydroxyapatite formation on a Ti-13Nb-13Zr alloy exposed in a MEM
      cell culture medium and the effect of H2O2 addition.
AB  - Titanium alloys are known to nucleate an apatite layer when in contact with
      simulated body fluid. This improves the bioactivity of titanium implants and
      accelerates osseointegration. Promoting the formation of hydroxyapatite on
      biocompatible metals is, therefore, a very important topic of biomaterials
      research. In this paper, the formation of hydroxyapatite (HA) on the near-beta Ti
      13Nb-13Zr alloy by immersion in minimal essential medium (MEM), with and without
      H(2)O(2) addition, has been studied using electrochemicals methods, scanning
      electron microscopy and X-ray photoelectron spectroscopy. The in vitro
      biocompatibility of this alloy was evaluated by cytotoxicity tests. The Ti-13Nb
      13Zr alloy exhibits passive behaviour over a wide potential range in MEM and the
      passive film is composed of an inner barrier layer and an outer porous layer. The
      addition of H(2)O(2) leads to a thickening of the outer porous layer and strongly
      reduced current density. With regard to the surface composition, immersion in MEM
      solution results in the formation of an island-like distribution of HA+amino
      acids. Addition of H(2)O(2) to the MEM solution strongly promotes the formation
      of a thicker, continuous but porous nanocomposite layer of HA+amino acids. The Ti
      13Nb-13Zr alloy is non-toxic and the nanocomposite HA+amino acid layer formed in
      the MEM solution favours the growth of osteoblast cells. For Ti alloys, the
      release of H(2)O(2) in the anti-inflammatory response appears to be an important
      beneficial process as it accelerates osseointegration.

PMID- 18815082
TI  - Our experience of vascular malformations masquerading as gastric stromal tumours.

PMID- 18815083
TI  - 'An approach to complex tracheostomal complications' by CJ Baldwin and MI
      Liddington--comment.

PMID- 18815084
TI  - Searching for the right timing of surgical delay: angiogenesis, vascular
      endothelial growth factor and perfusion changes in a skin-flap model.
AB  - BACKGROUND: The angiogenic potential of vascular endothelial growth factor (VEGF)
      and its oxygen pressure-dependent regulation suggest a strong connection between
      this growth factor and the 'delay phenomenon'. In this study we focused on the
      chronological changes in VEGF concentration and flap perfusion in order to
      optimise the duration of surgical delay. METHODS: The VEGF concentration in skin
      and underlying muscle was measured in oversized, random-pattern flaps on 38 male
      Sprague-Dawley rats after 3, 5 or 7 days of surgical delay. Additionally, flaps
      were raised 5 or 7 days past preconditioning. The effect on flap perfusion was
      measured using indocyanine green fluoroscopy and the size of surviving and
      necrotic areas of the flaps were analysed. Microvessel density was assessed using
      a monoclonal CD31 antibody, and vessel diameter and morphometry were appraised by
      means of corrosion casting. RESULTS: VEGF expression in the distal half of the
      flaps was significantly increased 3 days after preconditioning and perfusion was
      significantly enhanced after day 5. An interval of 5 days between preconditioning
      and flap transposition resulted in a significantly reduced average necrosis rate.
      Microvessel density was significantly increased and vessel diameters were
      enlarged (P<0.05). CONCLUSIONS: We illustrated the chronology of events from the
      ischaemic procedure to the rise in VEGF concentration and changes in flap
      perfusion, and demonstrated vasodilatation and the formation of new vessels. Most
      significantly, we were able to further specify the optimal length of surgical
      delay based on alterations on a molecular level as well as changes in
      vascularisation and perfusion.

PMID- 18815085
TI  - 'That's not erythema ab igne, that's a burn'.

PMID- 18815086
TI  - Easily obtainable clinical features increase the diagnostic accuracy for latent
      autoimmune diabetes in adults: an evidence-based report.
AB  - BACKGROUND: Latent autoimmune diabetes in adults (LADA) represents a subgroup of
      diabetes mellitus. LADA is characterised by adult-onset diabetes and circulating
      autoimmune antibodies. LADA patients may need a different therapeutic approach
      than the usual type 2 diabetes mellitus. When LADA is inadequately diagnosed as
      type 2 diabetes mellitus, LADA patients will mistakenly be exposed to a high dose
      of oral glucose lowering drugs and their possible side effects. AIM: To assess
      which clinical features predict the presence or absence of LADA in patients older
      than 25 years presenting with hyperglycemia. METHODS: A structured Medline and
      Embase search was conducted. Titles and abstracts were screened using
      predetermined selection criteria. Critical appraisal was based on standardized
      validity criteria for diagnostic research. RESULTS: One-hundred and eighty-four
      papers were retrieved of which after assessment of relevance and validity 2
      studies remained for further analysis. One study reported a probability of LADA
      of 0.99 with one or two out of the following five clinical features: age at onset
      <50 years; acute symptoms; BMI<25 kg/m(2); a history of autoimmune disease; a
      family history positive for diabetes mellitus. The other study reported a
      probability of LADA of zero with none of the following clinical features and of
      0.32 with one out of three: fasting blood glucose> or =15 mmol/l and/or HbA(1c)>
      or =10%; 10% reduction in body weight in the previous 3 months; BMI<25 kg/m(2).
      CONCLUSION: Further testing for LADA by measurement of autoimmune antibodies
      appears to be unnecessary in the absence of a specific set of clinical features.
      Before initiating therapy applying the above criteria may help to separate LADA
      from usual type 2 diabetes.

PMID- 18815087
TI  - [Atherosclerotic renal artery disease management update].
AB  - In the case of atherosclerotic renal artery disease, the best conclusive results
      lie principally not in the degree of the stenosis but rather in the degree the
      renal parenchymal disease beyond the stenosis itself. These determining factors
      involve the controlling of the patients blood pressure, the improvement in the
      renal function and the beneficial results to the cardiovascular system. Besides
      the indispensable medical treatment, a revascularisation by angioplasty may be
      indicated. This procedure with or without vascular stent often allows
      satisfactory angiographic results. A treatment by surgical revascularisation is
      only recommended in the case of extensive atherosclerotic lesions of the aorta,
      complex lesions of the latter or an abdominal aortic aneurism. Although the
      frequency of restenosis of angioplasty with stent remains extremely low, the risk
      of cholesterol emboli due to the diffuse atherosclerotic lesions of the abdominal
      aorta, must be considered at the time of each aortic catheterization. The
      therapeutic approach of atherosclerotic renal artery disease must be dictated by
      the whole cardiovascular risk factors and by the threat of target organs. The
      control of the blood pressure and the maintenance of the renal function must be
      integrated in the decisional algorithm as well as the possible risks in carrying
      out an eventual revascularisation procedure. Finally, the renal angioplasty
      should in numerous situations be integrated in the overall assumption of
      responsibility of the atherosclerotic vascular diseases, and should be part of
      the medical treatment. Several questions still do exist; at what moment an
      atherosclerotic renal artery stenosis should and e considered critical, and which
      procedure should be considered for which patient? The purpose of this review is
      to propose a decisional tool for individualized treatments in the light of
      results from randomized and controlled studies.

PMID- 18815088
TI  - [Dialin: infection surveillance network for haemodialysis patients. First
      results].
AB  - AIM AND BACKGROUND: To show results of the first year of an infection
      surveillance network for haemodialysis patients (Dialin). In order to improve the
      security and quality of care, six haemodialysis centers have organized an
      infection watching network. The purpose of the network is to compare of the
      watching results between centers. This comparison includes vascular access
      infection (VAI), bacteraemia and C viral hepatitis. The heterogeneous pattern has
      been also taken into account. SURVEY TYPE: Multicenter prospective permanent
      survey. POPULATION: Six hundred and sixty-four haemodialyzed chronic patients,
      followed during one year (2005), in six voluntary haemodialysis centers. This
      survey has based on 71,688 treatment sessions corresponding to 6257.5 months of
      haemodialysis (HM). METHODS: As with the heterogeneity among centers, the
      acquired infection standardized ratios (observed/expected) (AISR) and 95%
      confidence interval are computed with Cox model which includes confounding
      factors found in literature or in the preliminary stage of the survey. RESULTS:
      VAI crude rate was 0.47 per 100HM, 0.10 per 1000 native fistulae utilisation
      days, 0.45 per 1000 days of prosthetic graft utilisation and 0.44 per 1000 days
      of catheter utilisation. Bacteraemia crude incidence rate was 0.69 per 100HM,
      0.02 per 1000 days of native fistulae utilisation, 0.00 per 1000 days of
      prosthetic graft utilisation and 0.39 per 1000 days of catheter utilisation. No
      new case of C viral hepatitis was found. Prevalence rate at the beginning of the
      survey was 5.3% (35 over 664). Two centers had a significantly high AISR for VAI
      and two centers had a significantly low AISR for VAI. One center had a
      significantly high AISR for bacteraemia and one center had a significantly low
      AISR for bacteraemia. CONCLUSIONS: The first year of Dialin running demonstrates
      the importance of standardised surveillance method in VAI and bacteraemia
      surveillance but not for viral hepatitis.

PMID- 18815089
TI  - Ultrasound elastography: a dynamic programming approach.
AB  - This paper introduces a 2-D strain imaging technique based on minimizing a cost
      function using dynamic programming (DP). The cost function incorporates
      similarity of echo amplitudes and displacement continuity. Since tissue
      deformations are smooth, the incorporation of the smoothness into the cost
      function results in reduced decorrelation noise. As a result, the method
      generates high-quality strain images of freehand palpation elastography with up
      to 10% compression, showing that the method is more robust to signal
      decorrelation (caused by scatterer motion in high axial compression and nonaxial
      motions of the probe) in comparison to the standard correlation techniques. The
      method operates in less than 1 s and is thus also potentially suitable for real
      time elastography.

PMID- 18815090
TI  - A "twisting and bending" model-based nonrigid image registration technique for 3
      D ultrasound carotid images.
AB  - Atherosclerosis at the carotid bifurcation resulting in cerebral emboli is a
      major cause of ischemic stroke. Most strokes associated with carotid
      atherosclerosis can be prevented by lifestyle/dietary changes and pharmacological
      treatments if identified early by monitoring carotid plaque changes. Registration
      of 3-D ultrasound (US) images of carotid plaque obtained at different time points
      is essential for sensitive monitoring of plaque changes in volume and surface
      morphology. This registration technique should be nonrigid, since different head
      positions during image acquisition sessions cause relative bending and torsion in
      the neck, producing nonlinear deformations between the images. We modeled the
      movement of the neck using a "twisting and bending" model with only six
      parameters for nonrigid registration. We evaluated the algorithm using 3-D US
      carotid images acquired at two different head positions to simulate images
      acquired at different times. We calculated the mean registration error (MRE)
      between the segmented vessel surfaces in the target image and the registered
      image using a distance-based error metric after applying our "twisting and
      bending" model-based nonrigid registration algorithm. We achieved an average
      registration error of 0.80 +/-0.26 mm using our nonrigid registration technique,
      which was a significant improvement in registration accuracy over rigid
      registration, even with reduced degrees-of-freedom compared to the other nonrigid
      registration algorithms.

PMID- 18815091
TI  - Restoration of DWI data using a Rician LMMSE estimator.
AB  - This paper introduces and analyzes a linear minimum mean square error (LMMSE)
      estimator using a Rician noise model and its recursive version (RLMMSE) for the
      restoration of diffusion weighted images. A method to estimate the noise level
      based on local estimations of mean or variance is used to automatically
      parametrize the estimator. The restoration performance is evaluated using quality
      indexes and compared to alternative estimation schemes. The overall scheme is
      simple, robust, fast, and improves estimations. Filtering diffusion weighted
      magnetic resonance imaging (DW-MRI) with the proposed methodology leads to more
      accurate tensor estimations. Real and synthetic datasets are analyzed.

PMID- 18815092
TI  - Electrical impedance tomography problem with inaccurately known boundary and
      contact impedances.
AB  - In electrical impedance tomography (EIT) electric currents are injected into a
      body with unknown electromagnetic properties through a set of contact electrodes
      at the boundary of the body. The resulting voltages are measured on the same
      electrodes and the objective is to reconstruct the unknown conductivity function
      inside the body based on these data. All the traditional approaches to the
      reconstruction problem assume that the boundary of the body and the electrode
      skin contact impedances are known a priori. However, in clinical experiments one
      usually lacks the exact knowledge of the boundary and contact impedances, and
      therefore, approximate model domain and contact impedances have to be used in the
      image reconstruction. However, it has been noticed that even small errors in the
      shape of the computation domain or contact impedances can cause large systematic
      artefacts in the reconstructed images, leading to loss of diagnostically relevant
      information. In a recent paper (Kolehmainen , 2006), we showed how in the 2-D
      case the errors induced by the inaccurately known boundary can be eliminated as
      part of the image reconstruction and introduced a novel method for finding a
      deformed image of the original isotropic conductivity using the theory of
      TeichmUller mappings. In this paper, the theory and reconstruction method are
      extended to include the estimation of unknown contact impedances. The method is
      implemented numerically and tested with experimental EIT data. The results show
      that the systematic errors caused by inaccurately known boundary and contact
      impedances can efficiently be eliminated by the reconstruction method.

PMID- 18815093
TI  - Reduced encoding diffusion spectrum imaging implemented with a bi-Gaussian model.
AB  - Diffusion spectrum imaging (DSI) can map complex fiber microstructures in tissues
      by characterizing their 3-D water diffusion spectra. However, a long acquisition
      time is required for adequate q-space sampling to completely reconstruct the 3-D
      diffusion probability density function. Furthermore, to achieve a high q-value
      encoding for sufficient spatial resolution, the diffusion gradient duration and
      the diffusion time are usually lengthened on a clinical scanner, resulting in a
      long echo time and low signal-to-noise ratio of diffusion-weighted images. To
      bypass long acquisition times and strict gradient requirements, the reduced
      encoding DSI (RE-DSI) with a bi-Gaussian diffusion model is presented in this
      study. The bi-Gaussian extrapolation kernel, based on the assumption of the bi
      Gaussian diffusion signal curve across biological tissue, is applied to the
      reduced q-space sampling data in order to fulfill the high q-value requirement.
      The crossing phantom model and the manganese-enhanced rat model served as
      standards for accuracy assessment in RE-DSI. The errors of RE-DSI in estimating
      fiber orientations were close to the noise limit. Meanwhile, evidence from a
      human study demonstrated that RE-DSI significantly decreased the acquisition time
      required to resolve complex fiber orientations. The presented method facilitates
      the application of DSI analysis on a clinical magnetic resonance imaging system.

PMID- 18815094
TI  - Multispectral co-occurrence with three random variables in dynamic contrast
      enhanced magnetic resonance imaging of breast cancer.
AB  - Presented is a new computer-aided multispectral image processing method which is
      used in three spatial dimensions and one spectral dimension where the dynamic,
      contrast enhanced magnetic resonance parameter maps derived from voxel-wise model
      fitting represent the spectral dimension. The method is based on co-occurrence
      analysis using a 3-D window of observation which introduces an automated
      identification of suspicious lesions. The co-occurrence analysis defines 21
      different statistical features, a subset of which were input to a neural network
      classifier where the assessments of the voxel-wise majority of a group of
      radiologist readings were used as the gold standard. The voxel-wise true positive
      fraction (TPF) and false positive fraction (FPF) results of the computer
      classifier were statistically indistinguishable from the TPF and FPF results of
      the readers using a one sample paired t-test. In order to observe the generality
      of the method, two different groups of studies were used with widely different
      image acquisition specifications.

PMID- 18815095
TI  - A 4-channel coil array interconnection by analog direct modulation optical link
      for 1.5-T MRI.
AB  - Optical glass fiber shows great advantages over coaxial cables in terms of
      electromagnetic interference, thus, it should be considered a potential
      alternative for magnetic resonance imaging (MRI) receive coil interconnection,
      especially for a large number coil array at high field. In this paper, we propose
      a 4-channel analog direct modulation optical link for a 1.5-T MRI coil array
      interconnection. First, a general direct modulated optical link is compared to an
      external modulated optical link. And then the link performances of the proposed
      direct modulated optical link, including power gain, frequency response, and
      dynamic range, are analyzed and measured. Phantom and in vivo head images
      obtained using this optical link are demonstrated for comparison with those
      obtained by cable connections. The signal-to-noise (SNR) analysis shows that the
      optical link achieves 6%-8% SNR a improvement over coaxial cables by elimination
      of electrical interference between cables during MR signal transmission.

PMID- 18815096
TI  - Robust linearized image reconstruction for multifrequency EIT of the breast.
AB  - Electrical impedance tomography (EIT) is a developing imaging modality that is
      beginning to show promise for detecting and characterizing tumors in the breast.
      At Rensselaer Polytechnic Institute, we have developed a combined EIT
      tomosynthesis system that allows for the coregistered and simultaneous analysis
      of the breast using EIT and X-ray imaging. A significant challenge in EIT is the
      design of computationally efficient image reconstruction algorithms which are
      robust to various forms of model mismatch. Specifically, we have implemented a
      scaling procedure that is robust to the presence of a thin highly-resistive layer
      of skin at the boundary of the breast and we have developed an algorithm to
      detect and exclude from the image reconstruction electrodes that are in poor
      contact with the breast. In our initial clinical studies, it has been difficult
      to ensure that all electrodes make adequate contact with the breast, and thus
      procedures for the use of data sets containing poorly contacting electrodes are
      particularly important. We also present a novel, efficient method to compute the
      Jacobian matrix for our linearized image reconstruction algorithm by reducing the
      computation of the sensitivity for each voxel to a quadratic form. Initial
      clinical results are presented, showing the potential of our algorithms to detect
      and localize breast tumors.

PMID- 18815097
TI  - Hepatic perfusion imaging using factor analysis of contrast enhanced ultrasound.
AB  - Contrast enhanced ultrasound imaging provides a real-time tool for evaluating
      vasculature in the liver. Primary liver cancer is known to be perfused
      exclusively by blood from the hepatic artery, whereas normal liver is also
      supplied by the portal vein. Visual separation of two different phases of
      enhancement from the independent feeding vessels is important for diagnosis but
      remains a challenge. This paper presents a method of using factor analysis for
      extracting distinct time-intensity curves. A key component to this extraction is
      the clustering of measured bolus curves and their projection onto a positivity
      domain to obtain nonnegative curves. This technique provides complementary images
      representing spatial loadings on each curve. As little as 1% of the data is
      required to contain unmixed signals to extract time-intensity curves that
      correlate well with true curves. A method of combining this information to
      display a regional hepatic perfusion image is proposed, and results are tested on
      a set of 10 patients. Region of interest analysis suggests it is possible to
      detect changes in the hepatic perfusion index of liver lesions relative to normal
      liver parenchyma using contrast ultrasound.

PMID- 18815098
TI  - DT-MRI fiber tracking: a shortest paths approach.
AB  - We derive a new fiber tracking algorithm for DT-MRI that parts with the locally
      "greedy" paradigm intrinsic to conventional tracking algorithms. We demonstrate
      the ability to precisely reconstruct a diverse range of fiber trajectories in
      authentic and computer-generated DT-MRI data, for which well-known conventional
      tracking algorithms are shown to fail. Our approach is to pose fiber tracking as
      a problem in computing shortest paths in a weighted digraph. Voxels serve as
      vertices, and edges are included between neighboring voxels. We assign
      probabilities (weights) to edges using a Bayesian framework. Higher probabilities
      are assigned to edges that are aligned with fiber trajectories in their close
      proximity. We compute optimal paths of maximum probability using computationally
      scalable shortest path algorithms. The salient features of our approach are:
      global optimality--unlike conventional tracking algorithms, local errors do not
      accumulate and one "wrong-turn" does not spell disaster; a target point is
      specified a priori; precise reconstruction is demonstrated for extremely low
      signal-to-noise ratio; impartiality to which of two endpoints is used as a seed;
      and, faster computation times than conventional all-paths tracking. We can use
      our new tracking algorithm in either a single-path tracking mode (deterministic
      tracking) or an all-paths tracking mode (probabilistic tracking).

PMID- 18815099
TI  - Analysis of fMRI data using improved self-organizing mapping and spatio-temporal
      metric hierarchical clustering.
AB  - The self-organizing mapping (SOM) and hierarchical clustering (HC) methods are
      integrated to detect brain functional activation; functional magnetic resonance
      imaging (fMRI) data are first processed by SOM to obtain a primary merged neural
      nodes image, and then by HC to obtain further brain activation patterns. The
      conventional Euclidean distance metric was replaced by the correlation distance
      metric in SOM to improve clustering and merging of neural nodes. To improve the
      use of spatial and temporal information in fMRI data, a new spatial distance
      (node coordinates in the 2-D lattice) and temporal correlation (correlation
      degree of each time course in the exemplar matrix) are introduced in HC to merge
      the primary SOM results. Two simulation studies and two in vivo fMRI data that
      both contained block-design and event-related experiments revealed that brain
      functional activation can be effectively detected and that different response
      patterns can be distinguished using these methods. Our results demonstrate that
      the improved SOM and HC methods are clearly superior to the statistical
      parametric mapping (SPM), independent component analysis (ICA), and conventional
      SOM methods in the block-design, especially in the event-related experiment, as
      revealed by their performance measured by receiver operating characteristic (ROC)
      analysis. Our results also suggest that the proposed new integrated approach
      could be useful in detecting block-design and event-related fMRI data.

PMID- 18815100
TI  - Regularized field map estimation in MRI.
AB  - In fast magnetic resonance (MR) imaging with long readout times, such as echo
      planar imaging (EPI) and spiral scans, it is important to correct for the effects
      of field inhomogeneity to reduce image distortion and blurring. Such corrections
      require an accurate field map, a map of the off-resonance frequency at each
      voxel. Standard field map estimation methods yield noisy field maps, particularly
      in image regions with low spin density. This paper describes regularized methods
      for field map estimation from two or more MR scans having different echo times.
      These methods exploit the fact that field maps are generally smooth functions.
      The methods use algorithms that decrease monotonically a regularized least
      squares cost function, even though the problem is highly nonlinear. Results show
      that the proposed regularized methods significantly improve the quality of field
      map estimates relative to conventional unregularized methods.

PMID- 18815101
TI  - Intraretinal layer segmentation of macular optical coherence tomography images
      using optimal 3-D graph search.
AB  - Current techniques for segmenting macular optical coherence tomography (OCT)
      images have been 2-D in nature. Furthermore, commercially available OCT systems
      have only focused on segmenting a single layer of the retina, even though each
      intraretinal layer may be affected differently by disease. We report an automated
      approach for segmenting (anisotropic) 3-D macular OCT scans into five layers.
      Each macular OCT dataset consisted of six linear radial scans centered at the
      fovea. The six surfaces defining the five layers were identified on each 3-D
      composite image by transforming the segmentation task into that of finding a
      minimum-cost closed set in a geometric graph constructed from edge/regional
      information and a priori determined surface smoothness and interaction
      constraints. The method was applied to the macular OCT scans of 12 patients (24 3
      D composite image datasets) with unilateral anterior ischemic optic neuropathy
      (AION). Using the average of three experts' tracings as a reference standard
      resulted in an overall mean unsigned border positioning error of 6.1 +/- 2.9
      microm, a result comparable to the interobserver variability (6.9 +/- 3.3
      microm). Our quantitative analysis of the automated segmentation results from
      AION subject data revealed that the inner retinal layer thickness for the
      affected eye was 24.1 microm (21%) smaller on average than for the unaffected eye
      (p < 0.001), supporting the need for segmenting the layers separately.

PMID- 18815102
TI  - A note on the validity of statistical bootstrapping for estimating the
      uncertainty of tensor parameters in diffusion tensor images.
AB  - Diffusion tensors are estimated from magnetic resonance images (MRIs) that are
      diffusion-weighted, and those images inherently contain noise. Therefore, noise
      in the diffusion-weighted images produces uncertainty in estimation of the
      tensors and their derived parameters, which include eigenvalues, eigenvectors,
      and the trajectories of fiber pathways that are reconstructed from those
      eigenvalues and eigenvectors. Although repetition and wild bootstrap methods have
      been widely used to quantify the uncertainty of diffusion tensors and their
      derived parameters, we currently lack theoretical derivations that would validate
      the use of these two bootstrap methods for the estimation of statistical
      parameters of tensors in the presence of noise. The aim of this paper is to
      examine theoretically and numerically the repetition and wild bootstrap methods
      for approximating uncertainty in estimation of diffusion tensor parameters under
      two different schemes for acquiring diffusion weighted images. Whether these
      bootstrap methods can be used to quantify uncertainty in some diffusion tensor
      parameters, such as fractional anisotropy (FA), depends critically on the
      morphology of the diffusion tensor that is being estimated. The wild and
      repetition bootstrap methods in particular cannot quantify uncertainty in the
      principal direction (PD) of isotropic (or oblate) tensor. We also examine the use
      of bootstrap methods in estimating tensors in a voxel containing multiple
      tensors, demonstrating their limitations when quantifying the uncertainty of
      tensor parameters in those locations. Simulation studies are also used to
      understand more thoroughly our theoretical results. Our findings raise serious
      concerns about the use of bootstrap methods to quantify the uncertainty of fiber
      pathways when those pathways pass through voxels that contain either isotropic
      tensors, oblate tensors, or multiple tensors.

PMID- 18815103
TI  - A real-time 2-D vector Doppler system for clinical experimentation.
AB  - A real-time hardware software 2-D vector Doppler system has been realized by
      means of the FEMMINA platform. The system operates by performing two independent
      1-D Doppler estimations on the scan plane of a linear array probe along different
      directions; the probe is connected to a commercial scanner. The reconstructed
      velocity is presented in real-time as superposition on the conventional B-mode
      images. Two different scanning techniques have been implemented, in order to
      carry out the 2-D Doppler investigation in the area of interest. These techniques
      allow to use the system both in vivo and in vivo. An extensive set of simulations
      has been performed in order to establish a gold standard regarding vector Doppler
      2-D techniques, and to be able to assess the performance of the 2-D Doppler
      system by comparing simulated and experimental results. The whole real-time 2-D
      vector Doppler system is fully certified as hospital equipment, and thus it can
      be employed to carry out an experimental characterization of the 2-D Doppler
      technique in the clinical environment.

PMID- 18815104
TI  - Efficient segmentation by sparse pixel classification.
AB  - Segmentation methods based on pixel classification are powerful but often slow.
      We introduce two general algorithms, based on sparse classification, for
      optimizing the computation while still obtaining accurate segmentations. The
      computational costs of the algorithms are derived, and they are demonstrated on
      real 3-D magnetic resonance imaging and 2-D radiograph data. We show that each
      algorithm is optimal for specific tasks, and that both algorithms allow a speedup
      of one or more orders of magnitude on typical segmentation tasks.

PMID- 18815105
TI  - Toward realistic and practical ideal observer (IO) estimation for the
      optimization of medical imaging systems.
AB  - The ideal observer (IO) employs complete knowledge of the available data
      statistics and sets an upper limit on observer performance on a binary
      classification task. However, the IO test statistic cannot be calculated
      analytically, except for cases where object statistics are extremely simple.
      Kupinski have developed a Markov chain Monte Carlo (MCMC) based technique to
      compute the IO test statistic for, in principle, arbitrarily complex objects and
      imaging systems. In this work, we applied MCMC to estimate the IO test statistic
      in the context of myocardial perfusion SPECT (MPS). We modeled the imaging system
      using an analytic SPECT projector with attenuation, distant-dependent detector
      response modeling and Poisson noise statistics. The object is a family of
      parameterized torso phantoms with variable geometric and organ uptake parameters.
      To accelerate the imaging simulation process and thus enable the MCMC IO
      estimation, we used discretized anatomic parameters and continuous uptake
      parameters in defining the objects. The imaging process simulation was modeled by
      precomputing projections for each organ for a finite number of discretely
      parameterized anatomic parameters and taking linear combinations of the organ
      projections based on continuous sampling of the organ uptake parameters. The
      proposed method greatly reduces the computational burden and allows MCMC IO
      estimation for a realistic MPS imaging simulation. We validated the proposed IO
      estimation technique by estimating IO test statistics for a large number of input
      objects. The properties of the first- and second-order statistics of the IO test
      statistics estimated using the MCMC IO estimation technique agreed well with
      theoretical predictions. Further, as expected, the IO had better performance, as
      measured by the receiver operating characteristic (ROC) curve, than the Hotelling
      observer. This method is developed for SPECT imaging. However, it can be adapted
      to any linear imaging system.

PMID- 18815106
TI  - [Conservative treatment of benign prostatic hyperplasia].
AB  - Medical treatment of benign prostatic hyperplasia is reviewed by the author.
      Experiences with herbal extracts have been known for more than 2 decades.
      Treating benign prostatic hyperplasia with these extracts is recommended in
      initial phase. Prostate volume is decreased and mechanical component of dysuria
      is improved by treating for a long time (months, years) with 5-alpha-reductase
      finasteride which contains hormone. This drug is indicated when volume of the
      prostate is over 40 g. Dynamical component of benign prostatic hyperplasia is
      treated with alpha-receptor blockers which act on the bladder neck. These
      medicines have effects earlier and are recommended for all patients with benign
      prostatic hyperplasia independently of prostate volume. These might have some
      side effects like hypotension. The improving effects of 5-phosphodiesterase
      inhibitors on BPH have been discovered recently. The same effect has been
      described of alpha-blockers on sexual activity.

PMID- 18815107
TI  - [Reasons for proton-pump-inhibitor failure in the treatment of gastroesophageal
      reflux disease].
AB  - The introduction of proton pump inhibitors (PPI) has facilitated the successful
      management of patients with gastroesophageal reflux disease (GERD). In a minor,
      but still relevant proportion of patients with GERD-like symptoms, PPI therapy
      has also proved to be ineffective. In such cases, the first question to be
      answered is if the symptoms and complaints are related to GERD indeed, or another
      disorder should be searched for. If GERD is still the most likely diagnosis,
      patients' compliance should be thoroughly investigated before any further
      diagnostic and therapeutic measure is taken. If PPI failure is not a result of
      inadequate management of GERD, there are several other disorders to be ruled out.
      In our review, we summarize the most important differential diagnostic issues of
      PPI failure.

PMID- 18815108
TI  - [Surgical management with mitral valve replacement in young infants with
      congenital mitral valve diseases and complete atrioventricular septal defect].
AB  - OBJECTIVES: The mechanical valve replacement may be the only option if the
      failing mitral valve cannot be repaired in complete AV septal defect (CAVSD), or
      congenital mitral valve stenosis and regurgitation in infants. In young infants
      the small mitral annulus-prosthesis mismatch is a big problem. AIM: To assess the
      possibility of the left AV orifice repair and the necessity of mechanical valve
      replacement in CAVSD in young infants. METHODS: Single center, retrospective
      study of 82 infants (13 pts under 3 months) who underwent complete repair of
      CAVSD between 2001 and 2007. Mechanical (bileaflet) valve replacement was
      required in 7 pts (5 weeks-7 months, 3.5-5 kg). The time interval between the two
      operations was 0-7 days, but the smallest baby spent 38 days in the intensive
      care unit waiting for increasing of his mitral annulus size from 11 to 15 mm.
      (Types of implanted valves: 2 Carbomedics 16 mm, 3 ATS 16 mm, 1 Sorin 17 mm, 1
      Sorin 19 mm.) ATS 16 mm valves were implanted in 2 infants each with congenital
      mitral valve stenosis and regurgitation. RESULTS: Early mortality (30 days) was
      0, but 2 pts died in sepsis on the 46th and 71st postoperative day, respectively.
      In the follow-up period of 1-6 (mean 3) years 1 child (18 months later) needed
      reoperation (pannus removal), now all pts are doing well. Anticoagulation therapy
      was difficult in some cases without complication. CONCLUSIONS: The surgical
      repair of congenital mitral valve diseases and CAVSD can be performed
      successfully in very young infants. If the anatomic characteristics of the mitral
      valve is not suitable for repair, only mechanical mitral valve replacement can be
      performed successfully even in sometimes hopeless situation (one of our pts of
      3.5 kg weight, is the smallest baby mentioned in the literature). Our early and
      mid-time results are good, but the re-replacement will be an unavoidable problem
      in the future.

PMID- 18815109
TI  - [Beautiful girls' ugly malady--selected passages from the history of guilty sex
      and syphilis].
AB  - In Budapest at the end of the 19th century, visiting brothels was an important
      part of night life, including the risk of some venereal disease (v.d.) like
      syphilis, the in-vogue illness of the age. The expansion of prostitution could be
      explained with the continuous growth of economy and social development as a
      consequence of urbanization. Prostitution has grown in innumerable forms, levels
      and places in order to meet all requirements since this was the only tolerated
      form of sexuality "out of homes". The police headquarters' duty was to control
      the observation of rules prescribed for prostitutes. Data and information were
      available only on registered "professional" prostitutes because references on
      hidden prostitution were hard to find. Liberalization of the strict rules and
      regalements on brothels and "staff" began at the time when the increase of
      prostitution and simultaneously, of syphilis overreached the capacity of the
      Police and the Health Care System.

PMID- 18815110
TI  - [Double anniversary of ophthalmology professor Karoly Hoor (1858-1927)].

PMID- 18815111
TI  - [Memories and data related to the Hungarian Immunology Society, organized 50
      years ago].

PMID- 18815116
TI  - Extremely low genetic diversity in the endangered Hawaiian monk seal (Monachus
      schauinslandi).
AB  - Hunted to near extinction in the late 19th century, the endangered and endemic
      Hawaiian monk seal (Monachus schauinslandi) exhibits low variation at all
      molecular markers tested to date. Here we confirm extreme paucity of genetic
      diversity, finding polymorphisms at only 8 of 154 microsatellite loci tested (143
      novel species-specific loci, 10 loci from Antarctic seals, and 1 previously
      characterized locus). This screening revealed unprecedentedly low levels of
      allelic diversity and heterozygosity (A = 1.1, H(e) = 0.026). Subsequent analyses
      of 2409 Hawaiian monk seals at the 8 polymorphic loci provide evidence for a
      bottleneck (P = 0.002), but simulations indicate low genetic diversity (H(e) <
      0.09) prior to recorded human influence. There is little indication of
      contemporary inbreeding (F(IS) = 0.018) or population structure (K = 1
      population). Minimal genetic variation did not prevent partial recovery by the
      late 1950s and may not be driving the current population decline to approximately
      1200 seals. Nonetheless, genotyping nearly every individual living during the
      past 25 years sets a new benchmark for low genetic diversity in an endangered
      species.

PMID- 18815117
TI  - On the genetic control of heterosis for fruit shape in melon (Cucumis melo L.).
AB  - The objective of the present work is to study the genetic basis of heterosis for
      fruit shape (FS) in melon observed in a cross between the Spanish cultivar "Piel
      de Sapo" (PS) and the Korean accession PI 161375 (Songwang Charmi [SC]) using a
      set of near-isogenic lines (NILs) with contrasting phenotypes for FS, each
      carrying a single chromosomal introgression from SC within the genetic background
      of PS. We investigated the FS of homozygous NILs, hybrids NIL x PS, and all 2-way
      crosses between NILs to test the main heterosis hypotheses (dominance,
      overdominance, and epistatic interactions). Gene action of alleles of
      quantitative trait loci inducing fruit enlargement was dominance, whereas those
      inducing rounder fruit were additive or recessive. Only minor epistatic
      interactions were found. Therefore, the most plausible explanation for FS
      heterosis in this cross is in agreement with the dominance complementation
      hypothesis. Over 70% of the hybrid heterosis could be achieved by combining just
      2 loci, indicating that the genetic control of FS heterosis in this cross is
      relatively simple. FS is proposed as a reproductive trait in melon because of the
      high correlation to the number of seeds produced along the fruit longitudinal
      axis.

PMID- 18815118
TI  - Genetic variation revealed in the chloroplast-encoded RNA polymerase beta'
      subunit of downy mildew-resistant genotype of opium poppy.
AB  - Two accessions of opium poppy, Pps-1 (dark green leaves, highly resistant to
      downy mildew [DM]) and H-9 (yellowish green leaves, susceptible to DM), which
      originated from common progenitor SPS49 were selected, and their F(1) and F(2)
      progenies showed that leaf color trait was governed by single recessive nuclear
      gene, whereas DM resistance appeared to be the interaction between cytoplasmic
      and nuclear genes. Chloroplast DNA (cpDNA) analysis of these 2 accessions through
      arbitrarily-primed polymerase chain reaction generated a unique fragment in Pps
      1. Subsequent sequence analysis upon cloning of this cpDNA fragment revealed its
      similarity with the plastid-encoded RNA polymerase beta' subunit (rpoCI). Full
      length rpoCI DNA was therefore isolated from both the genotypes that was 2707 bp
      long with a 658-bp intron (436-1093) and a 2049-bp open reading frame encoding
      682 amino acid long polypeptide. Comparative sequence analysis of the rpoC1 gene
      from both the genotypes, revealed 4 single-nucleotide substitutions at 4
      positions that caused 3 amino acid changes in the protein sequence--1) A to C
      transversion at position 825 (Glu275Asp), 2) A to G transition at position 1203
      (Ile401Met), and 3) T to C transition at position 1422 and G to A transition at
      position 1423 both in same codon of the reading frame (Ala475Thr). This
      investigation is the first report indicating base substitution changes in the
      plastid-encoded rpoCI gene in DM-resistant genotypes of opium poppy. This finding
      may lead to implication of possible role of RNA polymerase beta' subunit in
      resistance to DM caused by Peronospora arborescens.

PMID- 18815119
TI  - Regulatory role of NKp44, NKp46, DNAM-1 and NKG2D receptors in the interaction
      between NK cells and trophoblast cells. Evidence for divergent functional
      profiles of decidual versus peripheral NK cells.
AB  - During the first trimester of pregnancy NK cells represent >50% of the lymphoid
      cells present in the human decidua where they reside in close contact with
      trophoblast cells. Because in decidual tissues NK cell activation and function
      may be induced by this interaction, we analyzed the cellular ligands recognized
      by activating NK receptors expressed on trophoblast cells. We show that these
      cells primarily express the NKp44 and DNAM-1 ligands and that interaction between
      these ligands and their corresponding receptors results in NK cell triggering.
      While activated peripheral blood NK (pNK) cells lysed the trophoblast cell lines
      JAR and JEG3, decidual NK (dNK) cells did not. On the other hand, they released
      VEGF, SDF-1, IP10 and large amounts of IL-8. Interaction with K562 target cells
      was exploited to induce optimal NK cell triggering, allowing a parallel,
      quantitative assessment of both cytolytic activity and cytokine production
      elicited by dNK cells. While dNK cells were unable to kill K562 even at high
      effector:target (E:T) ratios, they released large amounts of IL-8 also at low E:T
      ratios, a scenario compatible with dNK trophoblast cells interaction occurring
      within decidual tissues.

PMID- 18815120
TI  - Survival of human pre-antral follicles after cryopreservation of ovarian tissue,
      follicular isolation and in vitro culture in a calcium alginate matrix.
AB  - BACKGROUND: Ovarian tissue cryopreservation is a promising technique to safeguard
      fertility in cancer patients. However, in some types of cancer, there is a risk
      of transmitting malignant cells present in the cryopreserved tissue. To avoid
      such a risk, pre-antral follicles could be isolated from ovarian tissue and grown
      in vitro. On the basis of this assumption, the aim of our study was to
      investigate in vitro survival and growth of pre-antral follicles after
      cryopreservation of ovarian tissue and follicular isolation, followed by
      encapsulation in alginate beads. METHODS: Ovarian biopsies from four patients
      were frozen and thawed. Pre-antral follicles were then isolated and embedded in
      an alginate matrix before in vitro culture for 7 days. RESULTS: Small pre-antral
      follicles (42.98 +/- 9.06 microm) from frozen-thawed tissue can survive and
      develop after enzymatic isolation and in vitro culture. A total of 159 follicles
      were incubated in a three-dimensional system (alginate hydrogel) and, after 7
      days, all of them showed an increase in size (final size 56.73 +/- 13.10 microm).
      The survival rate of the follicles was 90% (oocyte and all granulosa cells
      viable). CONCLUSION: Our preliminary results indicate that alginate hydrogels may
      be a suitable system for in vitro culture of isolated human pre-antral follicles.
      However, more studies are required to establish whether follicular morphology and
      functionality can be maintained using this matrix.

PMID- 18815121
TI  - Genetic damage in wood dust-exposed workers.
AB  - Exposure to wood dust is common in carpentry workshops. Wood dust is known to be
      a human carcinogen, with a very high relative risk of adenocarcinoma of the nasal
      cavities and paranasal sinuses. The goal of this investigation was to conduct
      genotoxicity monitoring of carpenters involved in wooden furniture industry in
      order to test possible wood dust-induced genotoxic effects due to occupational
      exposure. The level of genetic damage was determined by comet, micronucleus and
      chromosomal aberration (CA) assays in peripheral blood lymphocytes (PBL) of 60
      carpentry workers. In addition, the micronucleus test in buccal epithelial cells
      was carried out in the same subjects. Total antioxidant enzyme activities were
      measured by the indices: superoxide dismutase, glutathione peroxidase and
      catalase. A group of 60 non-exposed subjects matched by age, smoking and alcohol
      consumption habits were chosen as controls. The effect of age, smoking, alcohol
      consumption and duration of exposure was also analysed in the subjects of the
      present study. The results showed a statistically significant increase in mean
      DNA damage by comet assay, micronuclei frequency in buccal cells as well as PBL
      and frequency of CA in the exposed workers when compared to controls (P < 0.05).
      Analysis of the data showed that all the confounding factors had a significant
      effect on DNA damage and micronucleus frequency in buccal epithelial cells and
      PBL. Smoking and alcohol consumption did not have any significant effect by
      chromosomal aberration test. Antioxidant enzyme levels significantly decreased in
      the exposed subjects. Our findings indicate enhanced levels of genotoxicity in
      carpenters. Hence, these workers may have an increased cancer risk.

PMID- 18815122
TI  - Modulation of genotoxicity and cytotoxicity by radish grown in metal-contaminated
      soils.
AB  - Members of the Brassicaceae family are known for their anticarcinogenic and
      genetic material protective effects. However, many of the species of this family
      accumulate high amounts of metals, which is an undesirable feature. Radish
      (Raphanus sativus L.) has shown to accumulate metals in roots to a higher extent
      than others members of Brassicaceae. The main objectives of this work are (i) to
      study the distribution of the accumulated As, Pb and Cd in radish plants and (ii)
      to establish the genotoxic, antigenotoxic and cytotoxic activities of the root
      and shoot of this vegetable. Results indicate that (i) the shoots of radish
      accumulate higher concentrations of metal(oid)s than roots; (ii) the shoots were
      genotoxic at the different concentrations studied, with the root showing such
      genotoxic effect only at the highest concentration assayed; (iii) the
      antigenotoxic potential of radish is reduced in plants with high metal content
      and (iv) the tumouricide activities of the radish plants were negatively
      correlated to their metal(oid) contents. An interaction between metal(oid)s and
      the isotyocianates (hydrolysis products of the glucosinolates) contained in the
      radish is suggested as the main modulator agents of the genotoxic activity of the
      plants grown in contaminated soils with metal(oid)s.

PMID- 18815123
TI  - Quantitative proteomics analysis of macrophage rafts reveals compartmentalized
      activation of the proteasome and of proteasome-mediated ERK activation in
      response to lipopolysaccharide.
AB  - Lipopolysaccharide (LPS), a glycolipid component of the outer membrane of Gram
      negative bacteria, is a potent initiator of the innate immune response of the
      macrophage. LPS triggers downstream signaling by selectively recruiting and
      activating proteins in cholesterol-rich membrane microdomains called lipid rafts.
      We applied proteomics analysis to macrophage detergent-resistant membranes (DRMs)
      during an LPS exposure time course in an effort to identify and validate novel
      events occurring in macrophage rafts. Following metabolic incorporation in cell
      culture of heavy isotopes of amino acids arginine and lysine ([(13)C(6)]Arg and
      [(13)C(6)]Lys) or their light counterparts, a SILAC (stable isotope labeling with
      amino acids in cell culture)-based quantitative, liquid chromatography-tandem
      mass spectrometry proteomics approach was used to profile LPS-induced changes in
      the lipid raft proteome of RAW 264.7 macrophages. Unsupervised network analysis
      of the proteomics data set revealed a marked representation of the ubiquitin
      proteasome system as well as changes in proteasome subunit composition following
      LPS challenge. Functional analysis of DRMs confirmed that LPS causes selective
      activation of the proteasome in macrophage rafts and proteasome inactivation
      outside of rafts. Given previous reports of an essential role for proteasomal
      degradation of IkappaB kinase-phosphorylated p105 in LPS activation of ERK
      mitogen-activated protein kinase, we tested for a role of rafts in
      compartmentalization of these events. Immunoblotting of DRMs revealed proteasome
      dependent activation of MEK and ERK specifically occurring in lipid rafts as well
      as proteasomal activity upon raft-localized p105 that was enhanced by LPS.
      Cholesterol extraction from the intact macrophage with methyl-beta-cyclodextrin
      was sufficient to activate ERK, recapitulating the LPS-IkappaB kinase-p105-MEK
      ERK cascade, whereas both it and the alternate raft-disrupting agent nystatin
      blocked subsequent LPS activation of the ERK cascade. Taken together, our
      findings indicate a critical, selective role for raft compartmentalization and
      regulation of proteasome activity in activation of the MEK-ERK pathway.

PMID- 18815124
TI  - Temporal perturbation of tyrosine phosphoproteome dynamics reveals the system
      wide regulatory networks.
AB  - Signal transduction systems are known to widely regulate complex biological
      events such as cell proliferation and differentiation. Because phosphotyrosine
      dependent networks play a key role in transmitting signals, a comprehensive and
      fine description of their dynamic behavior can lead us to systematically analyze
      the regulatory mechanisms that result in each biological effect. Here we
      established a mass spectrometry-based framework for analyzing tyrosine
      phosphoproteome dynamics through temporal network perturbation. A highly time
      resolved description of the epidermal growth factor-dependent signaling pathways
      in human A431 cells revealed a global view of their multiphase network
      activation, comprising a spike signal transmission within 1 min of ligand
      stimulation followed by the prolonged activation of multiple Src-related
      molecules. Temporal perturbation of Src family kinases with the corresponding
      inhibitor PP2 in the prolonged activation phase led to the down-regulation of the
      molecules related to cell adhesion and receptor degradation, whereas the
      canonical cascades as well as the epidermal growth factor receptor relatively
      maintained their activities. Our methodology provides a system-wide view of the
      regulatory network clusters involved in signal transduction that is essential to
      refine the literature-based network structures for a systems biology analysis.

PMID- 18815125
TI  - Regulation dynamics of WGD genes during yeast metabolic oscillation.
AB  - Saccharomyces cerevisiae and its close relatives are characterized by their
      propensity to ferment even in the presence of oxygen. It was hypothesized that
      whole-genome duplication (WGD) led to the development of this efficient
      fermentative lifestyle (WGD-fermentation hypothesis, Piskur 2001. In this study,
      we found that a significantly higher proportion of WGD genes than non-WGD genes
      are dynamically regulated during metabolic oscillation in response to oxygen
      change. The same data set also shows that the WGD genes, as compared with the
      smaller scale duplicate genes, are enriched with pairs where both copies have
      cyclic expression during the metabolic oscillation (either with the same or
      different phases). These results provide new evidences for the WGD-fermentation
      hypothesis and new insights into the relationship between the genome duplication
      and the evolution of new lifestyles in eukaryotic organisms.

PMID- 18815126
TI  - Histone N-terminal tails interfere with nucleosome traversal by RNA polymerase
      II.
AB  - We determined the effect of the N-terminal histone tails on nucleosome traversal
      by yeast and human RNA polymerase II (pol II). Removal of H2A/H2B tails, H3/H4
      tails, or all tails increased complete traversal of the nucleosome by human pol
      II, although the increase varied considerably depending on the template and on
      which tails were removed. Human pol II achieved >80% traversal of one nucleosomal
      template lacking the H2A/H2B tails, but even in those reactions, the transcript
      elongation rate was lower than the rate on pure DNA templates. For yeast pol II,
      transcription proceeded much farther into the nucleosome in the absence of tails,
      but complete read-through was not substantially increased by tail removal.
      Transcription factor IIS provided roughly the same level of read-through
      stimulation for transcript elongation in the presence or absence of tails. FACT
      also stimulated elongation on nucleosomal templates, and this effect was similar
      regardless of the presence of tails. For both polymerases, removal of the H2A/H2B
      tails reduced pausing throughout the nucleosome, suggesting that histone tails
      affect a common step at most points during nucleosome traversal. We conclude that
      histone tails provide a significant part of the nucleosomal barrier to pol II
      transcript elongation.

PMID- 18815127
TI  - Kinase networks integrate profiles of N-methyl-D-aspartate receptor-mediated gene
      expression in hippocampus.
AB  - The postsynaptic N-methyl-d-aspartate (NMDA) receptor activates multiple kinases
      and changes the phosphorylation of many postsynaptic proteins organized in
      signaling networks. Because the NMDA receptor is known to regulate gene
      expression, it is important to examine whether networks of kinases control
      signaling to gene expression. We examined the requirement of multiple kinases and
      NMDA receptor-interacting proteins for gene expression in mouse hippocampal
      slices. Protocols that induce long-term depression (LTD) and long-term
      potentiation (LTP) activated common kinases and overlapping gene expression
      profiles. Combinations of kinases were required for induction of each gene.
      Distinct combinations of kinases were required to up-regulate Arc, Npas4, Egr2,
      and Egr4 following either LTP or LTD protocols. Consistent with the combinatorial
      data, a mouse mutant model of the human cognition disease gene SAP102, which
      couples ERK kinase to the NMDA receptor, showed deregulated expression of
      specific genes. These data support a network model of postsynaptic integration
      where kinase signaling networks are recruited by differential synaptic activity
      and control both local synaptic events and activity-dependent gene expression.

PMID- 18815128
TI  - CHP2 activates the calcineurin/nuclear factor of activated T cells signaling
      pathway and enhances the oncogenic potential of HEK293 cells.
AB  - CHP2 (calcineurin B homologous protein 2) was initially identified as a tumor
      associated antigen highly expressed in hepatocellular carcinoma. Its biological
      function remains largely unknown except for a potential role in transmembrane
      Na(+)/H(+) exchange. In the present study, we observed that ectopic expression of
      CHP2 promoted the proliferation of HEK293 cells, whereas knockdown of endogenous
      CHP2 expression in HepG2 inhibited cell proliferation. When inoculated into nude
      mice, CHP2 transfected HEK293 cells displayed markedly increased oncogenic
      potential. In analysis of the underlying molecular mechanisms, we found that like
      calcineurin B, CHP2 was able to bind to and stimulate the phosphatase activity of
      calcineurin A. In accord with this, CHP2-transfected cells showed increased
      nuclear presence of NFATc3 (nuclear factor of activated T cells) and enhanced
      NFAT activity. Finally, both accelerated cell proliferation and NFAT activation
      following CHP2 transfection could be suppressed by the calcineurin inhibitor
      cyclosporine A, suggesting an intrinsic connection between these events. Taken
      together, our results highlighted a potential role of CHP2 in tumorigenesis and
      revealed a novel function of CHP2 as an activator of the calcineurin/NFAT
      signaling pathway.

PMID- 18815129
TI  - Effects of grape seed-derived polyphenols on amyloid beta-protein self-assembly
      and cytotoxicity.
AB  - Epidemiological evidence suggests that moderate consumption of red wine reduces
      the incidence of Alzheimer disease (AD). To study the protective effects of red
      wine, experiments recently were executed in the Tg2576 mouse model of AD. These
      studies showed that a commercially available grape seed polyphenolic extract,
      MegaNatural-AZ (MN), significantly attenuated AD-type cognitive deterioration and
      reduced cerebral amyloid deposition (Wang, J., Ho, L., Zhao, W., Ono, K.,
      Rosensweig, C., Chen, L., Humala, N., Teplow, D. B., and Pasinetti, G. M. (2008)
      J. Neurosci. 28, 6388-6392). To elucidate the mechanistic bases for these
      observations, here we used CD spectroscopy, photo-induced cross-linking of
      unmodified proteins, thioflavin T fluorescence, size exclusion chromatography,
      and electron microscopy to examine the effects of MN on the assembly of the two
      predominant disease-related amyloid beta-protein alloforms, Abeta40 and Abeta42.
      We also examined the effects of MN on Abeta-induced cytotoxicity by assaying 3
      [4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide metabolism and lactate
      dehydrogenase activity in Abeta-treated, differentiated pheochromocytoma (PC12)
      cells. Initial studies revealed that MN blocked Abeta fibril formation.
      Subsequent evaluation of the assembly stage specificity of the effect showed that
      MN was able to inhibit protofibril formation, pre-protofibrillar oligomerization,
      and initial coil --> alpha-helix/beta-sheet secondary structure transitions.
      Importantly, MN had protective effects in assays of cytotoxicity in which MN was
      mixed with Abeta prior to peptide assembly or following assembly and just prior
      to peptide addition to cells. These data suggest that MN is worthy of
      consideration as a therapeutic agent for AD.

PMID- 18815130
TI  - Stabilization and characterization of a heme-oxy reaction intermediate in
      inducible nitric-oxide synthase.
AB  - Nitric-oxide synthases (NOS) are heme-thiolate enzymes that N-hydroxylate L
      arginine (L-Arg) to make NO. NOS contain a unique Trp residue whose side chain
      stacks with the heme and hydrogen bonds with the heme thiolate. To understand its
      importance we substituted His for Trp188 in the inducible NOS oxygenase domain
      (iNOSoxy) and characterized enzyme spectral, thermodynamic, structural, kinetic,
      and catalytic properties. The W188H mutation had relatively small effects on l
      Arg binding and on enzyme heme-CO and heme-NO absorbance spectra, but increased
      the heme midpoint potential by 88 mV relative to wild-type iNOSoxy, indicating it
      decreased heme-thiolate electronegativity. The protein crystal structure showed
      that the His188 imidazole still stacked with the heme and was positioned to
      hydrogen bond with the heme thiolate. Analysis of a single turnover L-Arg
      hydroxylation reaction revealed that a new heme species formed during the
      reaction. Its build up coincided kinetically with the disappearance of the enzyme
      heme-dioxy species and with the formation of a tetrahydrobiopterin (H4B) radical
      in the enzyme, whereas its subsequent disappearance coincided with the rate of l
      Arg hydroxylation and formation of ferric enzyme. We conclude: (i) W188H iNOSoxy
      stabilizes a heme-oxy species that forms upon reduction of the heme-dioxy species
      by H4B. (ii) The W188H mutation hinders either the processing or reactivity of
      the heme-oxy species and makes these steps become rate-limiting for l-Arg
      hydroxylation. Thus, the conserved Trp residue in NOS may facilitate formation
      and/or reactivity of the ultimate hydroxylating species by tuning heme-thiolate
      electronegativity.

PMID- 18815131
TI  - Role of the HIV gp120 conserved domain 1 in processing and viral entry.
AB  - The importance of the N-terminal region of HIV gp120 conserved domain 1 (gp120
      C1) to envelope function has been examined by alanine-scanning mutagenesis and
      subsequent characterization of the mutagenic effects on viral entry; envelope
      expression, processing, and incorporation; and gp120 association with gp41. With
      respect to the wild-type gp120, mutational effects on viral entry fall into two
      classes: functional, as defined by >20% entry with respect to wild type, and
      impaired, as defined by <20% entry with respect to wild type. Based on Western
      blot analyses of cell lysates and virions, the entry impairment of W35A, V38A,
      Y39A, Y40A, G41A, V42A, and I52A is due primarily to disruption of envelope
      processing. The entry impairment of P43A and W45A is apparently due to a
      combination of effects on processing and incorporation into virions. In contrast,
      the entry impairment of V44A and F53A is primarily due to disruption of the gp120
      gp41 interaction, which results in dissociation of gp120 from the virion. We
      present a model for gp120-C1 interactions with gp120-C5 and the gp41 disulfide
      loop in unprocessed gp160 and processed gp120/gp41.

PMID- 18815132
TI  - The catalytic activity of protein-disulfide isomerase requires a conformationally
      flexible molecule.
AB  - Protein-disulfide isomerase (PDI) catalyzes the formation of the correct pattern
      of disulfide bonds in secretory proteins. A low resolution crystal structure of
      yeast PDI described here reveals large scale conformational changes compared with
      the initially reported structure, indicating that PDI is a highly flexible
      molecule with its catalytic domains, a and a', representing two mobile arms
      connected to a more rigid core composed of the b and b' domains. Limited
      proteolysis revealed that the linker between the a domain and the core is more
      susceptible to degradation than that connecting the a' domain to the core. By
      restricting the two arms with inter-domain disulfide bonds, the molecular
      flexibility of PDI, especially that of its a domain, was demonstrated to be
      essential for the enzymatic activity in vitro and in vivo. The crystal structure
      also featured a PDI dimer, and a propensity to dimerize in solution and in the ER
      was confirmed by cross-linking experiments and the split green fluorescent
      protein system. Although sedimentation studies suggested that the self
      association of PDI is weak, we hypothesize that PDI exists as an interconvertible
      mixture of monomers and dimers in the endoplasmic reticulum due to its high
      abundance in this compartment.

PMID- 18815133
TI  - Depurination of Brome mosaic virus RNA3 in vivo results in translation-dependent
      accelerated degradation of the viral RNA.
AB  - Pokeweed antiviral protein (PAP) is a ribosome-inactivating protein isolated from
      the pokeweed plant (Phytolacca americana) that exhibits antiviral activity
      against several plant and animal viruses. We have shown previously that PAP
      depurinates Brome mosaic virus (BMV) RNAs in vitro and that prior incubation of
      these RNAs with PAP reduced their synthesis in barley protoplasts. To investigate
      the post-transcriptional effect of PAP on viral RNA in vivo, we transcribed BMV
      RNA3 and expressed PAP in the yeast, Saccharomyces cerevisiae, which is a
      surrogate host for BMV. With an inducible transcription system, we show that the
      half-life of RNA3 in PAP-expressing cells was significantly less than in cells
      expressing PAPx, its enzymatically inactive form. PAP bound to RNA3 and
      depurinated the RNA within open reading frames 3 and 4 and within untranslated
      regions of the RNA. The depurinated RNA was associated with polysomes, caused
      ribosomes to stall at the point of depurination, and was targeted for accelerated
      degradation by components of the No-go decay pathway. As a consequence of
      translation elongation arrest and increased RNA degradation, expression of PAP in
      yeast also decreased the level of protein 3a, encoded by the 5'-proximal open
      reading frame 3 of BMV RNA3. These data provide the first evidence of viral RNA
      depurination in vivo by any ribosome-inactivating protein and support our
      hypothesis that depurination contributes to the antiviral activity of PAP, by
      enhancing viral RNA degradation and reducing translation of viral protein
      product.

PMID- 18815134
TI  - COP1 functions as a FoxO1 ubiquitin E3 ligase to regulate FoxO1-mediated gene
      expression.
AB  - COP1 is a Ring-Finger E3 ubiquitin ligase that is involved in plant development,
      mammalian cell survival, growth, and metabolism. Here we report that COP1, whose
      expression is enhanced by insulin, regulates FoxO1 protein stability. We found
      that in Fao hepatoma cells, ectopic expression of COP1 decreased, whereas
      knockdown of COP1 expression increased the level of endogenous FoxO1 protein
      without impacting other factors such as C/EBPalpha and CREB (cAMP-response
      element-binding protein). We further showed that COP1 binds FoxO1, enhances its
      ubiquitination, and promotes its degradation via the ubiquitin-proteasome
      pathway. To determine the biological significance of COP1-mediated FoxO1 protein
      degradation, we have examined the impact of COP1 on FoxO1-mediated gene
      expression and found that COP1 suppressed FoxO1 reporter gene as well as FoxO1
      target genes such as glucose-6-phosphatase and phosphoenolpyruvate carboxykinase,
      two key targets for FoxO1 in the regulation of gluconeogenesis, with
      corresponding changes of hepatic glucose production in Fao cells. We suggest that
      by functioning as a FoxO1 E3 ligase, COP1 may play a role in the regulation of
      hepatic glucose metabolism.

PMID- 18815135
TI  - Removal of the N-terminal extension of cardiac troponin I as a functional
      compensation for impaired myocardial beta-adrenergic signaling.
AB  - Although beta-adrenergic stimuli are essential for myocardial contractility, beta
      blockers have a proven beneficial effect on the treatment of heart failure, but
      the mechanism is not fully understood. The stimulatory G protein alpha-subunit
      (Gsalpha) couples the beta-adrenoreceptor to adenylyl cyclase and the
      intracellular cAMP response. In a mouse model of conditional Gsalpha deficiency
      in the cardiac muscle (Gsalpha-DF), we demonstrated heart failure phenotypes
      accompanied by increases in the level of a truncated cardiac troponin I (cTnI-ND)
      from restricted removal of the cTnI-specific N-terminal extension. To investigate
      the functional significance of the increase of cTnI-ND in Gsalpha-DF cardiac
      muscle, we generated double transgenic mice to overexpress cTnI-ND in Gsalpha-DF
      hearts. The overexpression of cTnI-ND in Gsalpha-DF failing hearts increased
      relaxation velocity and left ventricular end diastolic volume to produce higher
      left ventricle maximum pressure and stroke volume. Supporting the hypothesis that
      up-regulation of cTnI-ND is a compensatory rather than a destructive myocardial
      response to impaired beta-adrenergic signaling, the aberrant expression of beta
      myosin heavy chain in adult Gsalpha-DF but not control mouse hearts was reversed
      by cTnI overexpression. These data indicate that the up-regulation of cTnI-ND may
      partially compensate for the cardiac inefficiency in impaired beta-adrenergic
      signaling.

PMID- 18815136
TI  - Direct interaction between NM23-H1 and macrophage migration inhibitory factor
      (MIF) is critical for alleviation of MIF-mediated suppression of p53 activity.
AB  - Macrophage migration inhibitory factor (MIF) is a pluripotent cytokine that is
      involved in host immune and inflammatory responses, as well as tumorigenesis.
      However, the regulatory mechanism of MIF function is unclear. Here we report that
      the NM23-H1 interacts with MIF in cells, as demonstrated by cotransfection and
      coimmunoprecipitation experiments. Analysis of cysteine (Cys) to serine (Ser)
      substitution mutants of NM23-H1 (C4S, C109S, and C145S) and MIF (C57S, C60S, and
      C81S) revealed that Cys(145) of NM23-H1 and Cys(60) of MIF are responsible for
      complex formation. NM23-H1-MIF complexes were dependent on reducing conditions,
      such as the presence of dithiothreitol or beta-mercaptoethanol, but not H(2)O(2).
      NM23-H1 alleviated the MIF-mediated suppression of p53-induced apoptosis and cell
      cycle arrest by promoting the dissociation of MIF from MIF-p53 complexes. In
      addition, NM23-H1 significantly inhibited the MIF-induced proliferation of
      quiescent NIH 3T3 cells through a direct interaction with MIF, and decreased the
      MIF-induced activation of phosphatidylinositol 3-kinase/PDK1 and p44/p42
      extracellular signal-regulated (ERK) mitogen-activated protein kinase. The
      results of the current study suggest that the NM23-H1 functions as a negative
      regulator of MIF.

PMID- 18815137
TI  - Are all low molecular weight heparins equivalent in the management of venous
      thromboembolism?
AB  - Low molecular weight heparins are replacing unfractionated heparin in a number of
      clinical indications because of their improved subcutaneous bioavailability and
      more predictable antithrombotic response. Clinical trials have demonstrated that
      low molecular weight heparins are at least as safe and effective as
      unfractionated heparin for the initial treatment of venous thromboembolism, and
      unfractionated heparin and warfarin for primary and secondary thromboprophylaxis.
      The mechanism behind the antithrombotic action of low molecular weight heparins
      is not fully understood but is likely to involve inhibition of coagulation
      factors Xa and IIa (thrombin), release of tissue-factor-pathway inhibitor, and
      inhibition of thrombin activatable fibrinolytic inhibitor. Different low
      molecular weight heparins have been shown to have various effects on coagulation
      parameters. Seven low molecular weight heparins are currently marketed worldwide,
      each demonstrated distinct chemical entities with unique pharmacokinetic and
      pharmacodynamic profiles. Each low molecular weight heparin is approved for
      specific indications based on the available efficacy and safety data for that
      product. The relative efficacy and safety of the low molecular weight heparins
      are unclear because there have been very few direct comparisons in randomized
      clinical trials. While recommending low molecular weight heparins for the
      prevention and treatment of venous thromboembolism, clinical guidelines have not
      specified individual agents. National and international organizations recognize
      that low molecular weight heparins are distinct entities and that they should not
      be used interchangeably in clinical practice. Each low molecular weight heparin
      should be used at the recommended dose when efficacy and safety data exist for
      the condition being treated. When these data are not available, the dosing and
      administration of low molecular weight heparins must be adapted from existing
      data and recommendations.

PMID- 18815138
TI  - Contaminated heparin preparations, severe adverse events and the contact system.

PMID- 18815142
TI  - The respiratory local lymph node assay as a tool to study respiratory
      sensitizers.
AB  - The local lymph node assay (LLNA) is used to test the potential of low molecular
      weight (LMW) compounds to induce sensitization via the skin. In the present
      study, a respiratory LLNA was developed. Male BALB/c mice were exposed head/nose
      only during three consecutive days for 45, 90, 180, or 360 min/day to various LMW
      allergens. Ear application (skin LLNA) was used as a positive control. Negative
      controls were exposed to the vehicle. Three days after the last exposure,
      proliferation was determined in the draining mandibular lymph nodes, and the
      respiratory tract was examined microscopically. Upon inhalation, the allergens
      trimellitic anhydride, phthalic anhydride, hexamethylene diisocyanate, toluene
      diisocyanate, isophorone diisocyanate (IPDI), dinitrochlorobenzene, and oxazolone
      were positive and showed stimulation indices (SIs) up to 11, whereas trimeric
      IPDI, formaldehyde, and methyl salicylate were negative (viz. SI < 3). All
      compounds, except trimeric IPDI, induced histopathological lesions predominantly
      in the upper respiratory tract. Exposure by inhalation is a realistic approach to
      test respiratory allergens. However, based on the local toxicity, the dose that
      can be applied is (generally) much lower than can be achieved by skin
      application. It is concluded that strong LMW allergens, regardless their
      immunological nature, besides the skin can also sensitize the body via the
      respiratory tract. In addition, the contact allergens were as potent as the
      respiratory allergens, although the potency ranking differed from that in a skin
      LLNA.

PMID- 18815141
TI  - Methylmercury toxicity and Nrf2-dependent detoxification in astrocytes.
AB  - Methylmercury (MeHg) is a potent neurotoxicant and preferentially induces
      oxidative injury in astrocytes. In neuronal tissues, nuclear factor erythroid 2
      related factor 2 (Nrf2) is a key factor determining the protective antioxidant
      response against various environmental toxicants. Nrf2 is subjected to regulation
      by many other signaling pathways. The purpose of this study is to characterize
      its interaction with the phosphatidylinositol 3 (PI3) kinase in cultured rat
      neonatal primary astrocytes. The results showed that at pathologically relevant
      concentrations, exposure of primary astrocytes to MeHg led to Nrf2 activation and
      upregulation of its downstream antioxidant genes. Inhibition of the PI3 kinase
      resulted in decreased Nrf2 activity, decreased cellular glutathione, and
      increased cell death to high-dose MeHg. The functional interaction between the
      two signaling pathways underlined an important mechanism for astrocyte protection
      against MeHg toxicity. Modulation of Nrf2 by pharmacological modalities should
      afford a treatment to attenuate MeHg-induced neurotoxicity.

PMID- 18815143
TI  - Feel better. Live better. Get better.

PMID- 18815144
TI  - Biological mediators of effect of diet and stress reduction on prostate cancer.
AB  - BACKGROUND: A 6-month pilot intervention trial was conducted to determine whether
      adoption of a plant-based diet, reinforced by stress reduction, could reduce the
      rate of prostate-specific antigen (PSA) increase, a marker of disease
      progression, in asymptomatic, hormonally untreated patients experiencing
      consistently increasing PSA levels after surgery or radiation. METHODS: A pre
      post design was used to examine (1) the effect of intervention on potential
      mediators of disease progression, including body composition and weight-related
      biomarkers (sex steroid hormones and cytokines), and (2) whether changes in these
      variables were associated with change in rate of PSA increase. The baseline rate
      of PSA increase (from the time of posttreatment recurrence to the start of
      intervention) was ascertained from medical records. Body composition and
      biomarkers were assessed at baseline (prior to intervention), during the
      intervention (3 months), and at the end of the intervention (6 months). Changes
      in body composition and biomarkers were determined and compared with rates of PSA
      increase over the corresponding time intervals. RESULTS: There was a significant
      reduction in waist-to-hip ratio (P=.03) and increase in circulating sex hormone
      binding globulin (P=.04). The rate of PSA increase decreased from the
      preintervention period (PSA slope=0.059) to the period from 0 to 3 months (PSA
      slope=0.002, P<.01) and increased slightly, although not significantly, from 0 to
      3 months to the period from 3 to 6 months (0.029, P=.43). CONCLUSIONS: Adoption
      of a plant-based diet and stress reduction may reduce central adiposity and
      improve the hormonal milieu in patients with recurrent PC. Changes in the rate of
      increase in PSA were in the same direction as changes in waist-to-hip ratio and
      opposite those of sex hormone binding globulin, raising the possibility that the
      effect of the intervention may have been mediated, in part, by these variables.

PMID- 18815145
TI  - Role of religiosity and spirituality in complementary and alternative medicine
      use among cancer survivors in California.
AB  - OBJECTIVES: Cancer survivors often turn to religion, spirituality, and
      complementary and alternative medicine (CAM) because they perceive these areas as
      being more holistic and patient-centered than conventional medicine. Because
      increased religiosity and spirituality have been found to be associated with
      higher CAM use in the general population, it was hypothesized that these factors
      would be important predictors of CAM use in cancer survivors. DESIGN AND
      SUBJECTS: The study included a subsample of 1844 people with cancer or a history
      of cancer from the 2003 California Health Interview Survey of CAM, a cross
      sectional survey of a population-based sample of adults in California. Prevalence
      and predictors of religious/spiritual forms of CAM (R/S CAM) and
      nonreligious/nonspiritual forms of CAM (non-R/S CAM) were compared. Multivariate
      logistic regression was used to identify the predictors of R/S CAM and non-R/S
      CAM. RESULTS: Nearly two thirds of participants reported using at least 1 type of
      R/S CAM, and 85% reported ever using non-R/S CAM. The majority of cancer
      survivors reported that they were very/moderately religious or spiritual. Both
      religiosity and spirituality were strongly related to non-R/S CAM use, but in
      opposite directions. Very or moderately religious cancer survivors were less
      likely (odds ratio=0.30; 95% confidence interval, 0.12-0.40) than nonreligious
      cancer survivors to use non-R/S CAM. In contrast, very or moderately spiritual
      cancer survivors were more likely (odds ratio=2.42; 95% confidence interval, 1.16
      6.02) than nonspiritual cancer survivors to use non-R/S CAM. CONCLUSIONS: The use
      of R/S CAM and non-R/S CAM is very high in cancer survivors. It may be helpful
      for clinicians to ascertain their patients' use of these types of CAM to
      integrate all forms of care used to managing their cancer.

PMID- 18815146
TI  - Acute exercise protects against doxorubicin cardiotoxicity.
AB  - Numerous methods have been used to minimize the cardiotoxic effects of the
      chemotherapeutic agent doxorubicin (DOX), and most have had limited success.
      Chronic endurance exercise has been shown to protect against DOX cardiotoxicity,
      but little is known regarding the effects of acute exercise on DOX-induced
      cardiac dysfunction. PURPOSE: The purpose of this study was to determine the
      effects of a single bout of acute endurance exercise on the cardiac dysfunction
      associated with DOX treatment. METHODS: Male Sprague-Dawley rats either performed
      an acute exercise bout on a motorized treadmill for 60 minutes at a maximal speed
      of 25 m/min with a 5% grade (EX) or remained sedentary (SED) 24 hours before
      receiving either a 15-mg/kg DOX bolus dose or saline (SAL). Cardiac function was
      then analyzed 5 days post injection using a Langendorff isolated perfused heart
      model. In addition, myocardial lipid peroxidation was analyzed as an indicator of
      oxidative stress. RESULTS: Doxorubicin treatment alone (SED+DOX) promoted a
      significant decline in end-systolic pressure (-35%), left ventricular developed
      pressure (-59%), and the maximal rate of left ventricular pressure development (
      43%) as well as a 45% increase in lipid peroxidation products when compared with
      SED+SAL (P<.05). Acute exercise 24 hours before DOX treatment, however, had a
      cardioprotective effect, as end-systolic pressure, left ventricular developed
      pressure, and the maximal rate of left ventricular pressure development were
      significantly higher in EX+DOX compared with SED+DOX (P<.05) and EX+DOX had
      similar levels of lipid peroxidation products as SED+SAL CONCLUSIONS: An acute
      exercise bout performed 24 hours before DOX treatment protected against cardiac
      dysfunction, and this exercise-induced cardioprotection may partly be explained
      by a reduction in the generation of reactive oxygen species.

PMID- 18815147
TI  - Amelioration of radiation-induced hematological and biochemical alterations by
      Alstonia scholaris (a medicinal plant) extract.
AB  - The radioprotective efficacy of a hydro-alcoholic extracted material from the
      bark of Alstonia scholaris (ASE) was studied in mice against radiation-induced
      hematological and biochemical alterations. Swiss albino mice were administered
      ASE (100 mg/kg body weight/d for 5 consecutive day) orally prior to whole-body
      gamma irradiation (7.5 Gy). Radiation exposure resulted in a significant decline
      (P<.001) in erythrocytes and hemoglobin until the third day, following a gradual
      recovery (ie, day 7), but these values did not reach normal values during the
      remainder of the animals' life span. Hematocrit percentage declined significantly
      (P<.001) until day 15. In contrast, ASE-pretreated irradiated animals had
      significantly higher erythrocyte, hematocrit, and hemoglobin values than the
      irradiated controls. Furthermore, a significant elevation in lipid peroxidation
      level over normal was recorded in gamma-irradiated mice, whereas this increase
      was considerably lower in ASE-pretreated animals. Pretreatment with ASE caused a
      significant increase in glutathione levels in serum as well as in liver in
      comparison to irradiated animals. This study showed that ASE protects against
      radiation-induced hematological and biochemical alterations in Swiss albino mice.

PMID- 18815148
TI  - A retrospective evaluation of the effects of deuterium depleted water consumption
      on 4 patients with brain metastases from lung cancer.
AB  - HYPOTHESES: Because of the number of sufferers and high mortality rate, the
      standard care and new therapeutic options in the treatment of brain metastasis
      from lung cancer are the subject of intense research. A new concept based on the
      different chemical and physical behavior of protium and deuterium affecting cell
      signaling and tumor growth has been introduced in the treatment of cancer
      patients. The aim of this study was to investigate the impact of deuterium
      depleted water (DDW) consumption in addition to conventional forms of therapy on
      the survival of lung cancer patients with brain metastasis. STUDY DESIGN: A
      series of 4 case histories was retrospectively evaluated. The patients were
      diagnosed with brain metastasis deriving from a primary lung tumor and started
      consuming DDW at the time of or after the diagnosis of the brain metastasis,
      which was inoperable or the surgical intervention did not result in complete
      regression. The primary objective was survival. METHODS: The daily water intake
      of the patients was replaced with DDW, which complemented the conventional forms
      of treatment. Patients were consuming DDW for at least 3 months. The treatment
      was continued with DDW of 10 to 15 to 20 ppm lower deuterium (D) content every 1
      to 2 months and thus a gradual decrease was maintained in the D-concentration in
      the patient's body. RESULTS: DDW consumption integrated into conventional
      treatments resulted in a survival time of 26.6, 54.6, 21.9, and 33.4 months in
      the 4 patients, respectively. The brain metastasis of 2 patients showed complete
      response (CR), whereas partial response (PR) was detected in 1 patient, and the
      tumor growth was halted (no change or NC) in 1 case. The primary tumor of 2
      patients indicated CR, and the lung tumor in 2 patients showed PR. CONCLUSIONS:
      DDW was administered as an oral anticancer agent in addition to conventional
      therapy, and noticeably prolonged the survival time of all 4 lung cancer patients
      with brain metastasis. We suggest that DDW treatment, when integrated into other
      forms of cancer treatment, might provide a new therapeutic option.

PMID- 18815149
TI  - Review of the best case series methodology: best case series results of East-West
      Cancer Center.
AB  - PURPOSE: To assess the efficacy of the best case series program methodology as a
      preliminary evaluation of complementary and alternative programs. SETTING: East
      West Cancer Center (EWCC) is a traditional oriental cancer center located in
      Daejeon, Korea. Cancer patients received Wheel balance therapy (WBT), which
      focuses on rediscovering homeostatic harmony with dietary therapy, metabolism
      activating therapy, antiangiogenesis and immune system therapy, and controlled
      breathing and psychotherapy. METHODS: Summaries of 6 cases in which patients
      showed longer survival without progression and were treated with WBT without
      conventional treatments were submitted for review to the National Cancer
      Institute (NCI) Office of Cancer Complementary and Alternative Medicine. Each
      case was then classified by the NCI review panel with pathologic confirmation of
      disease and radiologic confirmation of complete response or partial response not
      attributable to conventional treatments. RESULTS: Two of 6 cases were classified
      as evaluable NCI best cases; the other 4 cases were classified as unevaluable.
      Except for a patient with squamous cell lung carcinoma, no patient showed further
      progression as of July 2007. CONCLUSION: The best case series program provides a
      preliminary evaluation of complementary and alternative medicine programs. But
      the method will only find treatments that have effects similar to those of
      conventional methods such as surgery, chemotherapy, and radiation therapy.
      Therefore, in future studies, BCSP reviewers should additionally consider
      assessing tumor dormancy and efficacy of combination therapies for Best Case
      qualification.

PMID- 18815150
TI  - Therapeutic actions of melatonin in cancer: possible mechanisms.
AB  - Melatonin is a phylogenetically well-preserved molecule with diverse
      physiological functions. In addition to its well-known regulatory control of the
      sleep/wake cycle, as well as circadian rhythms generally, melatonin is involved
      in immunomodulation, hematopoiesis, and antioxidative processes. Recent human and
      animal studies have now shown that melatonin also has important oncostatic
      properties. Both at physiological and pharmacological doses melatonin exerts
      growth inhibitory effects on breast cancer cell lines. In hepatomas, through its
      activation of MT1 and MT2 receptors, melatonin inhibits linoleic acid uptake,
      thereby preventing the formation of the mitogenic metabolite 1,3
      hydroxyoctadecadienoic acid. In animal model studies, melatonin has been shown to
      have preventative action against nitrosodiethylamine (NDEA)-induced liver cancer.
      Melatonin also inhibits the growth of prostate tumors via activation of MT1
      receptors thereby inducing translocation of the androgen receptor to the
      cytoplasm and inhibition of the effect of endogenous androgens. There is abundant
      evidence indicating that melatonin is involved in preventing tumor initiation,
      promotion, and progression. The anticarcinogenic effect of melatonin on
      neoplastic cells relies on its antioxidant, immunostimulating, and apoptotic
      properties. Melatonin's oncostatic actions include the direct augmentation of
      natural killer (NK) cell activity, which increases immunosurveillance, as well as
      the stimulation of cytokine production, for example, of interleukin (IL)-2, IL-6,
      IL-12, and interferon (IFN)-gamma. In addition to its direct oncostatic action,
      melatonin protects hematopoietic precursors from the toxic effect of anticancer
      chemotherapeutic drugs. Melatonin secretion is impaired in patients suffering
      from breast cancer, endometrial cancer, or colorectal cancer. The increased
      incidence of breast cancer and colorectal cancer seen in nurses and other night
      shift workers suggests a possible link between diminished secretion of melatonin
      and increased exposure to light during nighttime. The physiological surge of
      melatonin at night is thus considered a "natural restraint" on tumor initiation,
      promotion, and progression.

PMID- 18815151
TI  - Granulosa cell tumor of the ovary: tumor review.
AB  - Granulosa cell tumors of the ovary are rare neoplasms that originate from sex
      cord stromal cells. The long natural history of granulosa cell tumors and their
      tendency to recur years after the initial diagnosis are the most prominent of
      their characteristics. The secretion of estradiol is the reason for signs at
      presentation such as vaginal bleeding and precocious puberty. Abdominal pain and
      hemoperitoneum, which occasionally can occur, are attributable to tumor rupture.
      The most common finding in pelvic examination is a tumor mass, which is
      subsequently confirmed with imaging techniques. Surgery is the mainstay of
      initial management for histological diagnosis, appropriate staging, and
      debulking. A more conservative unilateral salpingo-oophorectomy is indicated in
      patients with stage I disease and patients of reproductive age. Total abdominal
      hysterectomy with bilateral salpingo-oophorectomy is the appropriate surgical
      treatment for postmenopausal women and those with more advanced disease. The
      stage of disease is the most important prognostic factor associated with the risk
      of relapse. There are no clear conclusions regarding the role of postoperative
      chemotherapy or radiotherapy in stage I disease and in those with completely
      resected tumor. The use of adjuvant chemotherapy or radiotherapy has sometimes
      been associated with prolonged disease-free survival and possibly overall
      survival. Chemotherapy is the treatment of choice for patients with advanced,
      recurrent, or metastatic disease, and BEP (bleomycin, etoposide, and cisplatin)
      is the preferred regimen. Although the overall rate of response to treatment is
      high, the impact of treatment on disease-free or overall survival is unknown.
      Prolonged surveillance is mandatory because tumors tend to recur years after the
      initial diagnosis.

PMID- 18815153
TI  - Effects of a modular behavioural arthritis education programme: a pragmatic
      parallel-group randomized controlled trial.
AB  - OBJECTIVES: Rheumatology guidelines recommend people with RA receive behavioural
      self-management education. This study developed a modular behavioural group
      programme and evaluated its longer term effects on pain, physical and
      psychological status. METHODS: People with RA or PsA were randomized to a modular
      behavioural or standard information-focused education programme, both delivered
      by experienced rheumatology health professionals at one large district general
      hospital. Outcome measures were pain, self-efficacy, fatigue, functional ability,
      psychological status and use of health behaviours (exercise, joint protection,
      fatigue and cognitive symptom management). Using an intent-to-treat analysis
      outcomes were compared at 6 and 12 months with analysis of covariance. RESULTS:
      Out of 498 referred patients, 218 agreed to participate, met entry criteria and
      were randomized; 51 withdrew before education. Of the remaining patients, 86
      attended the behavioural and 81 the standard programmes. Participants were aged
      55.4 yrs (s.d. 12.42) with disease duration of 7.39 (s.d. 6.88) yrs (53% <5 yrs).
      At 6 months, the behavioural group had better pain (P = 0.01), fatigue (P =
      0.01), functional ability (P = 0.05) and self-efficacy (P = 0.01) scores and
      greater use of health behaviours. At 12 months, they continued to have better
      pain (P = 0.03), self-efficacy (P = 0.001) and psychological status (P = 0.0001)
      scores and greater use of some health behaviours. CONCLUSION: Attending a modular
      behavioural education programme is effective for at least 1 yr in enabling people
      with RA and PsA to reduce pain, improve psychological status and self-manage
      their condition.

PMID- 18815152
TI  - Absence of the cellular prion protein exacerbates and prolongs neuroinflammation
      in experimental autoimmune encephalomyelitis.
AB  - Although the physiological roles of the cellular prion protein (PrP C) remain to
      be fully elucidated, PrP C has been proposed to represent a potential regulator
      of cellular immunity. To test this hypothesis, we evaluated the consequences of
      PrP C deficiency on the course of experimental autoimmune encephalomyelitis
      induced by immunization with myelin oligodendrocyte glycoprotein peptide.
      Consistent with augmented proliferative responses and increased cytokine gene
      expression by myelin oligodendrocyte glycoprotein-primed Prnp-/- T cells, PrP C
      deficient mice demonstrated more aggressive disease onset and a lack of clinical
      improvement during the chronic phase of experimental autoimmune
      encephalomyelitis. Acutely, Prnp-/- spinal cord, cerebellum, and forebrain
      exhibited higher levels of leukocytic infiltrates and pro-inflammatory cytokine
      gene expression, as well as increased spinal cord myelin basic protein and axonal
      loss. During the chronic phase, a remarkable persistence of leukocytic
      infiltrates was present in the forebrain and cerebellum, accompanied by an
      increase in interferon-gamma and interleukin-17 transcripts. Attenuation of T
      cell-dependent neuroinflammation thus represents a potential novel function of
      PrP C.

PMID- 18815154
TI  - Lack of association between Tenascin-C gene and spondyloarthritis.
AB  - OBJECTIVES: We previously identified a new susceptibility region linked to SpA in
      9q31-34. Tenascin-C (TNC) appears as one of the best positional and functional
      candidate genes lying within this SPA2 locus. The objectives of the present study
      were to identify TNC polymorphisms, and to examine their putative association
      with SpA. METHODS: We first performed variants screening in 20 independent SpA
      patients from families with high linkage score to the SPA2 locus, and three
      unrelated controls: TNCs coding regions (28 exons), intron-exon boundaries and 5'
      and 3'-flank regions were fully re-sequenced to identify polymorphisms. Then we
      genotyped selected variants in 183 independent trios, and assessed their
      intrafamilial association with SpA by transmission disequilibrium test. RESULTS:
      Variants screening allowed us to identify 26 polymorphisms, 7 of which were
      selected for further study, in addition to an intronic polymorphism previously
      reported as associated with Achilles tendon injuries. In intrafamilial
      association test, none of the variants showed significant transmission
      disequilibrium. Results from analysis restricted to AS were not different from
      those obtained on the whole SpA group. CONCLUSIONS: TNC was one of the best
      positional and functional candidate genes within the SPA2 locus. Nevertheless, we
      found no association between polymorphisms in this gene and SpA. However, we
      cannot exclude that variants located in intronic regions or in the vicinity of
      TNC, which were not tested in the present study, could be implicated in the
      predisposition to SpA.

PMID- 18815155
TI  - Increased susceptibility of serum amyloid A 1.1 to degradation by MMP-1:
      potential explanation for higher risk of type AA amyloidosis.
AB  - OBJECTIVE: Genetic polymorphisms in serum amyloid A (SAA) have been shown to
      substantially influence the risk of developing type AA amyloidosis. Recently, a
      role for MMP-1 has been suggested in the pathogenesis of AA amyloidosis.
      Therefore, we investigated if the SAA1 isotypes are differentially degraded by
      MMP-1. METHODS: Degradation of different SAA isotypes by MMP-1 was assessed by
      immunoblotting. MALDI-TOF mass spectrometry was used to identify degradation
      fragments. RESULTS: We found that SAA1.5 is more resistant to degradation by MMP
      1 than SAA1.1. This difference is caused by the capacity of MMP-1 to cleave at
      the site of the polymorphism at position 57. CONCLUSION: These results may
      explain the higher risk of amyloidosis in patients with a SAA1.1/1.1 genotype vs
      SAA1.5/1.5 or SAA1.1/1.5 genotype. In addition, the impaired degradation of
      SAA1.5 by MMP-1 could also explain the higher serum SAA concentrations in persons
      with a SAA1.5 genotype.

PMID- 18815156
TI  - A novel therapeutic approach to the treatment of scleroderma-associated pulmonary
      complications: safety and efficacy of combination therapy with imatinib and
      cyclophosphamide.
AB  - OBJECTIVE: Scleroderma-related interstitial lung disease (SSc-ILD) has limited
      therapeutic options due to unclear pathogenesis. Recently, PDGF receptor (PDGFR)
      amplification has been postulated to cause fibrosis. We hypothesized that a
      combination of immunosuppressive agents, e.g. cyclophosphamide (CYC) and imatinib
      (PDGFR inhibitor), might be useful for treating SSc-related ILD. Our objective
      was to evaluate the safety and efficacy of this combination therapy in
      scleroderma-related pulmonary disease. METHODS: Five patients with advanced SSc
      ILD underwent comprehensive cardiopulmonary evaluation, followed by
      administration of oral imatinib (200 mg/day) and intravenous CYC (500 mg every 3
      weeks). Safety was assessed by close monitoring of complete blood count, liver
      and cardiac functions. Efficacy was evaluated by measuring pulmonary functions at
      6 and 12 months. RESULTS: Of the five patients in the study, four had severe and
      one had mild restrictive lung disease. All patients tolerated the combination
      treatment without myelosuppression, deterioration of liver functions or cardiac
      status. Only one patient had mild fluid overload requiring diuretics. Two
      patients completed 1 yr of treatment. Only the patient with mild restrictive lung
      disease showed improvement in pulmonary function. CONCLUSION: The combination of
      intravenous CYC and oral imatinib was well-tolerated without major side effects.
      Clinical improvement was seen in only the patient with mild restrictive disease.
      To our knowledge, this is the first study examining the safety, tolerability and
      efficacy of imatinib in combination with CYC in scleroderma-related pulmonary
      disease. Large prospective trials are needed to further determine optimal timing,
      dose and duration of this regimen.

PMID- 18815157
TI  - Working ability in relation to disease severity, everyday occupations and well
      being in women with limited systemic sclerosis.
AB  - OBJECTIVE: To investigate how women with SSc and varying degrees of working
      ability differed regarding disease severity, everyday occupations and well-being.
      Working ability was operationalized according to the degree of sick leave.
      METHODS: Forty-four women of working age with lcSSc were assessed regarding
      sociodemographic characteristics, disease severity including organ manifestation,
      perceived physical symptoms, hand function, and satisfaction with everyday
      occupations, self-rated health and well-being. RESULTS: The subjects formed three
      groups with regard to reduction in working capacity. Twenty-one women (48%) had
      no sick leave, 15 women (34%) were on partial sick leave and eight women (18%)
      were temporarily on full-time sick leave or had a full disability pension. There
      were no statistically significant differences concerning sociodemographics
      between the groups. Women without sick leave had less physically demanding jobs
      (P = 0.026), and the hypothesis that working ability reflects lower disease
      severity was confirmed regarding dexterity grip force and perceived fatigue and
      breathlessness (P < 0.05). Greater working ability was associated with better
      capacity to perform activities of daily life (P < 0.01), greater satisfaction
      with occupations (P < 0.01), better well-being (P < 0.001) and better health (P <
      0.001). CONCLUSIONS: Fifty per cent of the women were restricted in their working
      ability; the lower the working ability, the lower their perceived well-being.
      This emphasizes the need for further research into the factors that promote
      working ability and the development of suitable methods to improve working
      ability.

PMID- 18815158
TI  - Two alternatively spliced GPR39 transcripts in seabream: molecular cloning,
      genomic organization, and regulation of gene expression by metabolic signals.
AB  - Two GPR39 transcripts, designated as sbGPR39-1a and sbGPR39-1b, were identified
      in black seabream (Acanthopagrus schlegeli). The deduced amino acid (aa) sequence
      of sbGPR39-1a contains 423 residues with seven putative transmembrane (TM)
      domains. On the other hand, sbGPR39-1b contains 284 aa residues with only five
      putative TM domains. Northern blot analysis confirmed the presence of two GPR39
      transcripts in the seabream intestine, stomach, and liver. Apart from seabream,
      the presence of two GPR39 transcripts was also found to exist in a number of
      teleosts (zebrafish and pufferfish) and mammals (human and mouse). Analysis of
      the GPR39 gene structure in different species suggests that the two GPR39
      transcripts are generated by alternative splicing. When the seabream receptors
      were expressed in cultured HEK293 cells, Zn(2)(+) could trigger sbGPR39-1a
      signaling through the serum response element pathway, but no such functionality
      could be detected for the sbGPR39-1b receptor. The two receptors were found to be
      differentially expressed in seabream tissues. sbGPR39-1a is predominantly
      expressed in the gastrointestinal tract. On the other hand, sbGPR39-1b is widely
      expressed in most central and peripheral tissues except muscle and ovary. The
      expression of sbGPR39-1a in the intestine and the expression of sbGPR39-1b in the
      hypothalamus were decreased significantly during food deprivation in seabream. On
      the contrary, the expression of the GH secretagogue receptors (sbGHSR-1a and
      sbGHSR-1b) was significantly increased in the hypothalamus of the food-deprived
      seabream. The reciprocal regulatory patterns of expression of these two genes
      suggest that both of them are involved in controlling the physiological response
      of the organism during starvation.

PMID- 18815161
TI  - Is prompt exploratory laparotomy the best attitude for mesenteric ischemia after
      cardiac surgery?
AB  - Mesenteric ischemia following cardiac surgery is a life-threatening complication.
      Early identification of patients may help optimizing management and improving
      outcome. Between January 2000 and July 2007, surgical exploration was realized
      when mesenteric ischemia was suspected after coronary-artery bypass grafts
      (CABG). Patients were divided in two groups according to diagnosis confirmation
      upon laparotomy. Peri-operative predictors of complication and death were
      analyzed. Of 1634 consecutive patients, 13 (0.8%) developed acute abdomen with
      suspicion of mesenteric ischemia. Seven (0.4%) underwent resection for ischemic
      lesions (group 1), of whom two were during a second look laparotomy. The other
      six patients had normal bowel (group 2). Both groups were comparable according to
      preoperative status, clinical signs, biological and radiological findings. Delays
      to laparotomy were 13.7+/-19.0 and 51.4+/-29.0 h in group 1 and 2, respectively
      (P=0.02). Mortality rates were 46.1% (6/13) overall, 42.8% for group 1 and 50%
      for group 2. All deaths occurred within the first nine postoperative days.
      Mesenteric ischemia following CABG is a fatal complication in almost half the
      cases. Diagnostic tools and timely laparotomy still need to be optimized. Low
      threshold-based strategy for prompt surgical intervention is efficient for both
      diagnosis and treatment.

PMID- 18815162
TI  - Penalised regression splines: theory and application to medical research.
AB  - Generalised additive models (GAMs) allow for flexible functional dependence of a
      response variable on covariates. The aim of this article is to provide an
      accessible overview of GAMs based on the penalised likelihood approach with
      regression splines. In contrast to the classical backfitting, the penalised
      likelihood framework taken here provides researchers with an efficient
      computational method for automatic multiple smoothing parameter selection, which
      can determine the functional form of any relationship from the data. We
      illustrate through an example how the use of this methodology can help to gain
      insights into medical research.

PMID- 18815163
TI  - A hierarchical zero-inflated log-normal model for skewed responses.
AB  - Although considerable attention has been given to zero-inflated count data,
      research on zero-inflated lognormal data is limited. In this article, we consider
      a study to examine human sperm cell DNA damage obtained from single-cell
      electrophoresis (COMET assay) experiment in which the outcome measures present a
      typical example of log-normal data with excess zeros. The problem is further
      complicated by the fact that each study subject has multiple outcomes at each of
      up to three visits separated by six-week intervals. Previous methods for zero
      inflated log-normal data are based on either simple experimental designs, where
      comparison of means of zero-inflated log-normal data across different experiment
      groups is of primary interest, or longitudinal measurements, where only one
      observation is available for each subject at each visit. Their methods cannot be
      applied when multiple observations per visit are possible and both inter- and
      intra-subject variations are present. Our zero-inflated model extends the
      previous methods by incorporating a hierarchical structure using latent random
      variables to take into account both inter- and intra-subject variations in zero
      inflated log-normal data. An EM algorithm has been developed to obtain the
      Maximum likelihood estimates of the parameters and their standard errors can be
      estimated by parametric bootstrap. The model is illustrated using the COMET assay
      data.

PMID- 18815164
TI  - Efficient sampling approaches to address confounding in database studies.
AB  - Administrative and other population-based databases are widely used in
      pharmacoepidemiology to study the unintended effects of medications. They allow
      investigators to study large case series, and they document prescription
      medication exposure without having to contact individuals or medical charts, or
      rely on human recall. However, such databases often lack information on
      potentially important confounding variables. This review describes some of the
      sampling approaches and accompanying data-analysis methods that can be used to
      assess, and deal efficiently with, such confounding.

PMID- 18815165
TI  - Evidence based medicine and the medical curriculum.

PMID- 18815170
TI  - Diagnosis and management of attention-deficit/hyperactivity disorder in children,
      young people, and adults: summary of NICE guidance.

PMID- 18815173
TI  - Guidelines call for HIV testing to be "normalised".

PMID- 18815171
TI  - Commentary: Controversies in NICE guidance on attention-deficit/hyperactivity
      disorder.

PMID- 18815174
TI  - London's catch-up vaccination campaign against measles, mumps, and rubella
      reaches less than a quarter of children who were unvaccinated.

PMID- 18815175
TI  - China's tainted infant formula sickens nearly 13,000 babies.

PMID- 18815176
TI  - Germany debates change to law on late abortions.

PMID- 18815177
TI  - Southall is allowed to return to child protection work.

PMID- 18815179
TI  - Headache and drowsiness in a 22 year old student.

PMID- 18815180
TI  - An interesting chest radiograph.

PMID- 18815183
TI  - A new rule-based algorithm for identifying metabolic markers in prostate cancer
      using tandem mass spectrometry.
AB  - MOTIVATION: Prostate cancer is the most prevalent tumor in males and its
      incidence is expected to increase as the population ages. Prostate cancer is
      treatable by excision if detected at an early enough stage. The challenges of
      early diagnosis require the discovery of novel biomarkers and tools for prostate
      cancer management. RESULTS: We developed a novel feature selection algorithm
      termed as associative voting (AV) for identifying biomarker candidates in
      prostate cancer data measured via targeted metabolite profiling MS/MS analysis.
      We benchmarked our algorithm against two standard entropy-based and correlation
      based feature selection methods [Information Gain (IG) and ReliefF (RF)] and
      observed that, on a variety of classification tasks in prostate cancer diagnosis,
      our algorithm identified subsets of biomarker candidates that are both smaller
      and show higher discriminatory power than the subsets identified by IG and RF. A
      literature study confirms that the highest ranked biomarker candidates identified
      by AV have independently been identified as important factors in prostate cancer
      development. AVAILABILITY: The algorithm can be downloaded from the following
      http://biomed.umit.at/page.cfm?pageid=516.

PMID- 18815184
TI  - Salvianolic acid B protects human endothelial cells from oxidative stress damage:
      a possible protective role of glucose-regulated protein 78 induction.
AB  - AIMS: The purposes of the present study were to both evaluate the protective
      effects of Salvianolic acid B (Sal B) and to determine the possible molecular
      mechanisms by which Sal B protects endothelial cells from damage caused by
      oxidative stress. METHODS AND RESULTS: Pretreatment with Sal B markedly
      attenuated H(2)O(2)-induced viability loss, lactate dehydrogenase leakage and
      apoptosis in human umbilical vein endothelial cells (HUVECs). The mechanism of
      Sal B protection was studied using two-dimensional gel electrophoresis coupled
      with hybrid quadrupole time-of-flight mass spectrometry. Database searching
      implicated that glucose-regulated protein 78 (GRP78), a central regulator for
      endoplasmic reticulum (ER) stress, was up-regulated in Sal B-exposed HUVECs.
      GRP78 expression regulation was confirmed by western blot and RT-PCR (reverse
      transcription-polymerase chain reaction) analyses. Additionally, GRP94, which
      shares significant sequence homology with GRP78, was also up-regulated in Sal B
      treated cells. Sal B caused pancreatic ER kinase (PKR)-like ER kinase (PERK)
      activation followed by the phosphorylation of eukaryotic translation initiation
      factor 2 alpha (eIF2 alpha) and the expression of activating transcription factor
      4 (ATF4). Knockdown of endogenous ATF4 expression partially repressed Sal B
      induced GRP78 induction. Further investigation showed that ATF6 was also
      activated by Sal B. Knockdown of GRP78 by siRNA significantly reduced the
      protective effects of Sal B. CONCLUSION: The results suggest that Sal B induces
      the expression of GRP78 by activating ATF6 and the PERK-eIF2 alpha-ATF4 pathway.
      Furthermore, up-regulation of GRP78 by Sal B may play an important role in
      protecting human endothelial cells from oxidative stress-induced cellular damage.

PMID- 18815185
TI  - Interaction between transcription factors Iroquois proteins 4 and 5 controls
      cardiac potassium channel Kv4.2 gene transcription.
AB  - AIMS: The homeobox transcription factor, Iroquois protein 5 (Irx5), plays an
      essential role in the generation of region-selective expression of Kv4.2 gene
      across the left ventricular wall of rodent hearts. Here, we analyse molecular
      mechanisms underlying the Irx5-induced regulation of the rat Kv4.2 promoter.
      METHODS AND RESULTS: The mRNA levels for Irx members in various heart regions
      were assessed by RT-PCR. A luciferase reporter gene with the rat Kv4.2 promoter
      was used to test the effects of Irx members on channel promoter activity. Irx3
      and Irx5 mRNAs were differentially distributed across the left ventricular wall,
      whereas Irx4 message was equally abundant in various ventricular regions. Irx5,
      but not Irx3 or Irx4, increased Kv4.2 promoter activity in 10T1/2 fibroblasts,
      whereas the transcription factor decreased promoter activity in neonatal
      ventricular myocytes. These effects were mediated by the C-terminal portion of
      Irx5. Irx4 appeared to inhibit the Irx5-induced increase in channel promoter
      activity in 10T1/2 cells. The N-terminal region of Irx4 was necessary and
      sufficient for this inhibition. Furthermore, when endogenous Irx4 expression was
      suppressed with siRNA, Irx5 increased channel promoter activity in neonatal
      myocytes. CONCLUSION: These results indicate that Irx5 possesses the ability to
      activate the Kv4.2 promoter. The abundant Irx4 expression throughout the rat
      ventricle may play a role in the inverse relationship between Irx5 and Kv4.2
      levels across the left ventricular wall.

PMID- 18815186
TI  - PARP-1 suppresses adiponectin expression through poly(ADP-ribosyl)ation of PPAR
      gamma in cardiac fibroblasts.
AB  - AIMS: Our aim was to explore the mechanism underlying the transcriptional
      regulation of adiponectin and its receptors (AdipoR) in cultured rat cardiac
      fibroblasts. METHODS AND RESULTS: Using western blot and real-time RT-PCR assays,
      the expression of adiponectin and its receptors was determined. Using
      Southwestern blot and electrophoretic mobility shift assays, the DNA binding
      activity of peroxisome proliferator activated receptor gamma (PPAR gamma) was
      determined. The results showed that adiponectin and AdipoR1 were highly expressed
      in cultured rat cardiac fibroblasts. Inhibition of poly(ADP-ribose) polymerase 1
      (PARP-1) by 3-aminobenzamide, PJ34, or PARP-1 siRNA markedly increased the
      transcription of adiponectin and AdipoR1 in cultured fibroblasts, mature 3T3 L1
      adipocytes, rat myocardium, and white adipose tissue. PPAR gamma was poly(ADP
      ribosyl)ated by PARP-1 in cardiac fibroblasts under basal conditions. Poly(ADP
      ribosyl)ation of PPAR gamma prevented its binding to DNA. Inhibition of PARP-1
      enhanced the DNA binding and transactivation of PPAR gamma and increased the
      transcription of PPAR gamma-target genes including CD36, lipoprotein lipase, and
      leptin in cultured fibroblasts. CONCLUSION: PARP-1 inhibits adiponectin and
      AdipoR1 expression as well as PPAR gamma transactivation through poly(ADP
      ribosyl)ation of PPAR gamma in cultured rat cardiac fibroblasts.

PMID- 18815187
TI  - Complete atrioventricular block in Duchenne muscular dystrophy.
AB  - Duchenne muscular dystrophy (DMD) is an inherited myogenic disorder due to
      mutations in the dystrophin gene on chromosome Xp21.1. It is characterized by
      progressive muscle wasting and weakness of variable distribution and severity.
      Heart is involved leading to heart failure. Conduction abnormalities are unusual.
      We report a case of complete atrio-ventricular block in a DMD patient.

PMID- 18815188
TI  - Discrimination of ventricular tachycardia from supraventricular tachycardia in
      implantable cardioverter defibrillators by automated electrogram morphology
      analysis: can leads finally replace the electrophysiologist?

PMID- 18815189
TI  - Nonsense mutations of the alpha-spectrin gene in hereditary pyropoikilocytosis.

PMID- 18815190
TI  - Enhanced alternative splicing of the FLVCR1 gene in Diamond Blackfan anemia
      disrupts FLVCR1 expression and function that are critical for erythropoiesis.
AB  - BACKGROUND: Diamond-Blackfan anemia is a fatal congenital anemia characterized by
      a specific disruption in erythroid progenitor cell development. Approximately 25%
      of patients have mutations in the ribosomal protein RPS19 suggesting that Diamond
      Blackfan anemia may be caused by a defect in ribosome biogenesis and translation.
      However, it is unclear how these defects specifically disrupt early
      erythropoiesis. Recent studies have shown that the retroviral receptor/heme
      exporter FLVCR1 is critical for early erythropoiesis. FLVCR1 null mice, despite
      dying in utero and having reduced myeloid and lymphoid cell growth, show a
      disruption in early erythropoiesis and have craniofacial and limb deformities
      similar to those found in some Diamond-Blackfan anemia patients. DESIGN AND
      METHODS: In this study, we recapitulated the Diamond-Blackfan anemia hematologic
      features of reduced erythropoiesis but normal myelopoiesis by disrupting FLVCR1
      in human hematopoietic stem cells. RESULTS: We found that CD71(high) cells, which
      are enriched for immature erythroid cells, from Diamond-Blackfan anemia patients
      negative for RPS19 gene mutations express alternatively spliced isoforms of
      FLVCR1 transcript which encode proteins whose expression and function are
      disrupted. More importantly, our results suggest alternative splicing of FLVCR1
      is significantly enhanced in Diamond-Blackfan anemia immature erythroid cells.
      Furthermore, we also observed enhanced FLVCR1 alternative splicing and a dramatic
      reduction of FLVCR1 protein expression in RPS19 down-regulated human K562 cells,
      which were used as a model to represent RPS19 gene mutated Diamond-Blackfan
      anemia. CONCLUSIONS: Taken together, our results suggest enhanced alternative
      splicing of FLVCR1 transcripts and subsequent FLVCR1 insufficiency as an
      additional contributing factor to the erythropoietic defect observed in Diamond
      Blackfan anemia.

PMID- 18815191
TI  - Anemia of chronic disease and defective erythropoietin production in patients
      with celiac disease.
AB  - BACKGROUND: Anemia due to hematinic deficiencies is common in patients with
      untreated celiac disease. Although celiac disease is a chronic condition
      characterized by an intense inflammatory response of the intestinal mucosa, scant
      data are available about the prevalence of anemia of chronic disease in celiac
      disease. DESIGN AND METHODS: One hundred and fifty-two patients with celiac
      disease at presentation were studied. Anemia was investigated by determining
      complete blood counts, body iron status, serum levels of the soluble transferrin
      receptor, erythropoietin, prohepcidin and interferon-gamma. Genotyping for HFE
      mutations associated with hereditary hemochromatosis was performed. Fifty-three
      anemic patients were re-evaluated for hematologic response after 1 year on a
      gluten-free diet. RESULTS: At the time of diagnosis of celiac disease the
      prevalence of anemia was 34%. Fifty-three out of 65 anemic patients had either
      iron and/or vitamin deficiency (folate, vitamin B(12)). Hereditary
      hemochromatosis mutations did not affect the prevalence of anemia. In 11 cases
      iron status parameters were indicative of anemia of chronic disease, sometimes in
      association with iron deficiency (6 patients). Patients with anemia of chronic
      disease had low levels of erythropoietin for the degree of anemia and increased
      serum interferon-gamma. In most cases anemia improved following a gluten-free
      diet, response rates being similar in anemia of chronic disease and in anemia due
      to hematinic deficiencies. CONCLUSIONS: Our study shows that, in addition to iron
      and vitamin deficiencies, anemia of chronic disease has a significant role in
      some patients with celiac disease. Suppression of intestinal inflammatory changes
      as a result of a gluten-free diet improves anemia by correcting iron and vitamin
      malabsorption as well as mechanisms contributing to anemia of chronic disease.

PMID- 18815192
TI  - The relevance of preferentially expressed antigen of melanoma (PRAME) as a marker
      of disease activity and prognosis in acute promyelocytic leukemia.
AB  - BACKGROUND: The gene for preferentially expressed antigen of melanoma (PRAME) has
      been shown to be over-expressed in acute promyelocytic leukemia, but its actual
      incidence and clinical impact are still unknown. DESIGN AND METHODS: We studied
      PRAME expression at diagnosis using real-time quantitative polymerase chain
      reaction in 125 patients with acute promyelocytic leukemia enrolled in the
      Spanish PETHEMA-96 (n=45) and PETHEMA-99 (n=80) clinical trials. In addition,
      PRAME expression was evaluated as a marker of disease activity in 225 follow-up
      samples from 67 patients with acute promyelocytic leukemia. RESULTS: At
      diagnosis, PRAME expression in patients with acute promyelocytic leukemia was
      significantly higher (p<0.001) than in patients with non-M3 acute myeloid
      leukemia (n=213) and in healthy controls (n=10). Furthermore, patients with acute
      promyelocytic leukemia with high PRAME expression had a favorable outcome. Thus,
      the 5-year relapse-free survival was better in patients with >100-fold PRAME
      expression (86% vs. 74%; p=0.03), and this cut-off established two sub-groups
      with different relapse-free survival rates among patients with a white cell count
      <10(9)/L (5-year relapse-free survival 94% vs. 80%, p=0.01). This effect was
      similar in patients with a white cell count >10(9)/L, although differences were
      not statistically significant. In multivariate analysis, white cell count
      >10(9)/L (p<0.001), bone marrow blasts >90% (p=0.001), and PRAME expression <100
      fold (p=0.009) were associated with short relapse-free survival. Samples at
      remission showed PRAME levels similar to those in normal controls while samples
      at relapse over-expressed PRAME again. Furthermore, 12/13 samples collected
      within the 6-month period preceding relapse showed a >10-fold increase in PRAME
      expression levels. CONCLUSIONS: Low PRAME expression defines a subgroup of
      patients with acute promyelocytic leukemia with a short relapse-free survival.
      This marker could be useful as a secondary marker for monitoring patients with
      acute promyelocytic leukemia.

PMID- 18815193
TI  - EVI1 overexpression in t(3;17) positive myeloid malignancies results from
      juxtaposition of EVI1 to the MSI2 locus at 17q22.
AB  - Chromosomal translocations involving the EVI1 locus are a recurrent finding in
      myeloid leukemia and are associated with poor prognosis. In this study, we
      performed a detailed molecular characterization of the recurrent translocation
      t(3;17)(q26;q22) in 13 hematologic malignancies. The EVI1 gene locus was
      rearranged in all 13 patients and was associated with EVI1 overexpression. In 9
      out of 13 patients, the 17q breakpoints clustered in a 250 kb region on band
      17q22 encompassing the MSI2 (musashi homologue 2) gene. Expression analyses
      failed to demonstrate ectopic MSI2 expression or the presence of an MSI2/EVI1
      fusion gene. In conclusion, we show for the first time that the t(3;17) is indeed
      a recurrent chromosomal aberration in myeloid malignancies. In keeping with
      findings in other recurrent 3q26 rearrangements, overexpression of the EVI1 gene
      appears to be the major contributor to leukemogenesis in patients with a t(3;17).

PMID- 18815194
TI  - Anemia and survival in childhood acute lymphoblastic leukemia.
AB  - BACKGROUND: Several studies have demonstrated that patients with childhood acute
      lymphoblastic leukemia presenting with mild anemia at diagnosis have an increased
      risk of poor outcome compared to patients with more severe anemia. However, it
      has not been reported whether there is any correlation between degree of anemia
      and leukemia subtype. DESIGN AND METHODS: In a cohort of 1162 patients with
      childhood acute lymphoblastic leukemia we analyzed whether there was a
      correlation between degree of anemia and leukemia subtype. We also studied the
      association between degree of anemia and event-free survival within the subtypes.
      RESULTS: Hemoglobin levels at diagnosis were distributed in a non-random pattern.
      The degree of anemia was significantly different for three distinct groups of
      patients compared to the remaining patients (mean hemoglobin; T-cell leukemia:
      106 g/L versus 76 g/L (precursor B-cell acute lymphoblastic leukemia); within
      precursor B-cell ALL: TEL-AML1 positive: 68 g/L versus 79 g/L; BCR-ABL positive:
      93 g/L versus 76 g/L; each p<0.05). Furthermore, in contrast to the entire study
      group, patients with T-cell leukemia, TEL-AML1(+), and BCR-ABL(+) precursor B
      cell leukemia had a more favorable prognosis if presenting with a higher
      hemoglobin level (>/=80 g/L). CONCLUSIONS: These observations indicate that the
      formerly reported direct correlation between severity of anemia and survival in
      childhood acute lymphoblastic leukemia mainly reflects differences in the degree
      of anemia between distinct biological subgroups with different treatment
      outcomes. On the other hand, the inverse relationship between severity of anemia
      and survival found within specific subgroups suggests that very low hemoglobin
      levels at diagnosis are associated with more advanced disease in these subgroups.

PMID- 18815195
TI  - Asthma is associated with acute chest syndrome, but not with an increased rate of
      hospitalization for pain among children in France with sickle cell anemia: a
      retrospective cohort study.

PMID- 18815196
TI  - Methylation of the suppressor of cytokine signaling 3 gene (SOCS3) in
      myeloproliferative disorders.
AB  - BACKGROUND: The JAK2 V617F mutation can be found in patients with polycythemia
      vera, essential thrombocythemia and idiopathic myelofibrosis. Mutation or
      methylation of other components of JAK/STAT signaling, such as the negative
      regulators suppressor of cytokine signaling 1 (SOCS1) and SOCS3, may contribute
      to the pathogenesis of both JAK2 V617F positive and negative myeloproliferative
      disorders. DESIGN AND METHODS: A cohort of patients with myeloproliferative
      disorders was assessed for acquired mutations, aberrant expression and/or CpG
      island hypermethylation of SOCS1 and SOCS3. RESULTS: No mutations were identified
      within the coding region of either gene in 73 patients with myeloproliferative
      disorders. No disease-specific CpG island methylation of SOCS1 was observed.
      SOCS1 expression was raised in myeloproliferative disorder granulocytes but the
      level was independent of JAK2 V617F status. Hypermethylation of the SOCS3
      promoter was identified in 16 of 50 (32%) patients with idiopathic myelofibrosis
      but not in patients with essential thrombocythemia, polycythemia vera or
      myelofibrosis preceded by another myeloproliferative disorder. Confirmation of
      methylation status was validated by nested polymerase chain reaction and/or
      bisulphite sequencing. SOCS3 transcript levels were highest in patients with
      polycythemia vera and other JAK2 V617F positive myeloproliferative disorders,
      consistent with SOCS3 being a target gene of JAK2/STAT5 signaling. There was a
      trend towards an association between SOCS3 methylation and lower SOCS3 expression
      in JAK2 V617F negative patients with idiopathic myelofibrosis but not in JAK2
      V617F positive ones. Finally, SOCS3 methylation was not significantly correlated
      with survival or other clinical variables. CONCLUSIONS: SOCS3 promoter
      methylation was detected in 32% of patients with idiopathic myelofibrosis
      suggesting a possible role for SOCS3 methylation in this disorder. The
      pathogenetic consequences of SOCS3 methylation in idiopathic myelofibrosis remain
      to be fully elucidated.

PMID- 18815197
TI  - Novel point mutation in a leucine-rich repeat of the GPIbalpha chain of the
      platelet von Willebrand factor receptor, GPIb/IX/V, resulting in an inherited
      dominant form of Bernard-Soulier syndrome affecting two unrelated families: the
      N41H variant.
AB  - In Italy, a significant proportion of patients with autosomal dominant
      inheritance of macrothrombocytopenia have been recognized as having heterozygous
      Bernard-Soulier syndrome carrying the Bolzano-type defect. This condition
      prompted a systematic review of our out-patients with chronic isolated
      macrothrombocytopenia. We recognized that the affected members of two unrelated
      families represented a new variant of heterozygous Bernard-Soulier Syndrome with
      autosomal dominant inheritance. Sequencing analysis of the GPIbalpha gene
      revealed a novel heterozygous mutation, A169C, resulting in an N41H substitution
      in the protein. This aminoacid belongs to the first leucine-rich repeat of the
      chain. The molecular modeling suggests that the replacement of the N41 with a
      histidine (N41H) drastically disturbs the structure of the first portion of
      GPIbalpha N-terminal, directly involved in von Willebrand factor binding. As a
      consequence, platelet aggregation to 1.2 mg/mL of ristocetin is slightly impaired
      and flow cytometry reveals a reduced binding of monoclonals directed against N
      terminal epitopes of the GPIbalpha.

PMID- 18815198
TI  - Mitochondrial ferritin limits oxidative damage regulating mitochondrial iron
      availability: hypothesis for a protective role in Friedreich ataxia.
AB  - Mitochondrial ferritin (FtMt) is a nuclear-encoded iron-sequestering protein that
      specifically localizes in mitochondria. In mice it is highly expressed in cells
      characterized by high-energy consumption, while is undetectable in iron storage
      tissues like liver and spleen. FtMt expression in mammalian cells was shown to
      cause a shift of iron from cytosol to mitochondria, and in yeast it rescued the
      defects associated with frataxin deficiency. To study the role of FtMt in
      oxidative damage, we analyzed the effect of its expression in HeLa cells after
      incubation with H(2)O(2) and Antimycin A, and after a long-term growth in glucose
      free media that enhances mitochondrial respiratory activity. FtMt reduced the
      level of reactive oxygen species (ROS), increased the level of adenosine
      5'triphosphate and the activity of mitochondrial Fe-S enzymes, and had a positive
      effect on cell viability. Furthermore, FtMt expression reduces the size of
      cytosolic and mitochondrial labile iron pools. In cells grown in glucose-free
      media, FtMt level was reduced owing to faster degradation rate, however it still
      protected the activity of mitochondrial Fe-S enzymes without affecting the
      cytosolic iron status. In addition, FtMt expression in fibroblasts from
      Friedreich ataxia (FRDA) patients prevented the formation of ROS and partially
      rescued the impaired activity of mitochondrial Fe-S enzymes, caused by frataxin
      deficiency. These results indicate that the primary function of FtMt involves the
      control of ROS formation through the regulation of mitochondrial iron
      availability. They are consistent with the expression pattern of FtMt observed in
      mouse tissues, suggesting a FtMt protective role in cells characterized by
      defective iron homeostasis and respiration, such as in FRDA.

PMID- 18815199
TI  - Health benefits in 2008: premiums moderately higher, while enrollment in consumer
      directed plans rises in small firms.
AB  - Our annual Employer Health Benefits Survey contains findings from interviews with
      1,927 public and private employers surveyed during the first five months of 2008.
      Average annual premiums in 2008 are $4,704 for single coverage and $12,680 for
      family coverage. These amounts are about 5 percent higher than premiums were last
      year. Enrollment in high-deductible health plans with a savings option increased
      to 8 percent of covered workers, up from 5 percent in 2007. Deductibles in
      preferred provider organizations, the plan type with the largest enrollment,
      increased from 2007 levels. This paper also provides new insights into firms'
      offering wellness programs and retiree health benefits.

PMID- 18815200
TI  - High levels of plasma malondialdehyde, protein carbonyl, and fibrinogen have
      prognostic potential to predict poor outcomes in patients with diabetic foot
      wounds: a preliminary communication.
AB  - Diabetic foot ulcer (DFU) is the leading cause of lower extremity amputation and
      is generally known to have poor prognosis. Oxidative stress is considered
      important in the pathogenesis of chronic wounds. Fibrinogen is a recognized
      marker in peripheral vascular disease; increasing levels predict an increased
      mortality and risk of amputation. The aim of this study was to evaluate if plasma
      malondialdehyde (MDA), protein carbonyl (PC) and fibrinogen levels can be used as
      prognostic markers in patients with DFU. The study design was prospective,
      nonrandomized, and controlled. A total of 41 DFU grade 1 and 20 DFU grade 2
      patients were studied in this case-control study. Diabetic controls without foot
      ulcers and healthy controls were also studied. Plasma MDA, PC, and fibrinogen
      levels were significantly higher in patients with DFU compared with those without
      ulcers (P < .05) and nondiabetic controls (P < .001). These parameters increased
      in association with DFU grade (P < .01). Increased levels of plasma fibrinogen,
      MDA, and PC correlated with worsened outcomes. An augmented oxidative stress and
      plasma fibrinogen level >300.4 mg% (95% confidence interval, 100% sensitivity,
      99.2% specificity) was correlated with a high risk of amputation in DFU.

PMID- 18815201
TI  - Leg wound infections following greater saphenous vein harvesting: minimally
      invasive vein harvesting versus conventional vein harvesting.
AB  - Wound complications associated with long incisions used to harvest the greater
      saphenous vein are common and well documented. We compared leg wound infection
      rates, wound healing disturbances (WHDs), length of vein harvested, vein harvest
      time, and total surgical time between minimally invasive saphenous vein
      harvesting (MIVH) and conventional vein harvesting (CVH) techniques. This meta
      analysis showed a significant reduction in wound infections in favor of the MIVH
      group (odds ratio = 0.19; 95% confidence interval = 0.14-0.25) and a significant
      reduction in WHDs in favor of the MIVH group (odds ratio = 0.26; 95% confidence
      interval = 0.20-0.34). The MIVH and CVH techniques are equivalent with respect to
      saphenous vein harvest time, saphenous vein harvest length, and total surgical
      time. A visual inspection of "funnel" plots suggests a mild to moderate
      publication bias. This meta-analysis suggests that leg wound infections and wound
      healing disturbances are reduced using MIVH techniques.

PMID- 18815202
TI  - Aggressive organ donor management protocol.
AB  - As of August 2007, 96 900 people are awaiting organ transplantation in the United
      States, while only 28 930 transplants were performed in 2006. With such a large
      gap between organ need and organ availability, it is inevitable that many will
      die while awaiting transplantation. This organ shortage has become a national
      public health crisis, and as a response, the United States Department of Health
      and Human Services launched the Organ Donation Breakthrough Collaborative, an
      ambitious campaign to dramatically increase the number of transplantable organs.
      One of the suggested strategies involves maximizing the number of organs obtained
      from the available cadaveric "brain dead'' donor pool by using donor management
      protocols that optimize and treat the profound physiological disturbances that
      are associated with brain death. The use of these standardized and aggressive
      donor management protocols has been shown to increase the number of transplanted
      organs and prevent the number of donors lost due to medical failures. A protocol
      driven approach by a dedicated organ donor management team should be considered a
      key component of any program designed to bridge the gap between organ supply and
      demand.

PMID- 18815203
TI  - B-cell cutaneous lymphoid hyperplasia representing progressive transformation of
      germinal center: a report of 2 cases.
AB  - Cutaneous lymphoid hyperplasia (CLH) is a reactive polyclonal benign
      lymphoproliferative process predominantly composed of B cells or T cells, either
      localized or disseminated. The authors report histomorphologic, immunophenotypic,
      and genotypic findings of 2 cases of B-cell CLH demonstrating progressive
      transformation of germinal center (PTGC). Histologically, most of the lymphoid
      follicles were PTGCs with a few hyperplastic germinal centers. PTGC was
      characterized by enlarged but well-circumscribed follicles without clear
      demarcation of the germinal center and mantle zone, which contained a
      predominance of small lymphocytes and variable numbers of centrocytes,
      centroblasts, and immunoblasts. However, there were no centroblasts and
      immunoblasts resembling lymphocytic and/or histiocytic Reed-Sternberg cell
      variants in nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) in either
      lesion. These unusual CLHs should be differentiated from the primary cutaneous
      marginal zone B-cell lymphoma, primary cutaneous follicular lymphoma,
      particularly "floral variant," or NLPHL. To avoid overdiagnosis and
      overtreatment, immunophenotypic and genotypic studies are required along with
      careful morphologic examination.

PMID- 18815204
TI  - Images in pathology. Art exemplified in pathology.

PMID- 18815205
TI  - Telemetric signal-driven servocontrol of renal perfusion pressure in acute and
      chronic rat experiments.
AB  - The present study was designed to take advantage of telemetry data acquisition
      and develop an easy and reliable system to servocontrol renal perfusion pressure
      (RPP). Digitized pressure signals from lower abdominal aorta in rats, reflecting
      RPP, was obtained by a telemetry device and dynamically exported into an Excel
      worksheet. A computer program (LabVIEW) compared the RPP data with a preselected
      pressure range and drove a bidirectional syringe pump to control the inflation of
      a vascular occluder around the aorta above renal arteries. When RPP was higher
      than the preselected range, the syringe pump inflated the occluder and decreased
      RPP, and vice versa. If RPP was within range, there was no action. In this way,
      RPP was servocontrolled within the desired range. In experiments with
      norepinephrine- or ANG II-induced acute increases in systemic arterial pressure
      (120-145 mmHg), the system controlled RPP at a constant range of 100-105 mmHg
      within 30-50 s and differentiated the pressure-dependent and -independent effects
      on renal functions. In Dahl S rats with high-salt-induced hypertension, this
      system maintained RPP at 100-120 mmHg over 10 days, while systemic arterial
      pressures were 150 +/- 5.9 mmHg in uncontrolled animals. This system also has the
      ability of simultaneity and multiplexing to control multiple animals. Our results
      suggest that this is an effective and reliable system to servocontrol RPP, which
      can be easily established with general computer knowledge. This system provides a
      powerful tool and may greatly facilitate the studies in pressure-dependent/
      independent effects of a variety of cardiovascular factors.

PMID- 18815206
TI  - Human vastus lateralis and soleus muscles display divergent cellular contractile
      properties.
AB  - The purpose of this study was to investigate potential differences in single
      fiber contractile physiology of fibers with the same myosin heavy chain isoform
      (MHC I and MHC IIa) originating from different muscles. Vastus lateralis (VL) and
      soleus biopsies were obtained from 27 recreationally active females (31 +/- 1 yr,
      59 +/- 1 kg). A total of 943 single fibers (MHC I = 562; MHC IIa = 301) were
      isolated and examined for diameter, peak tension (Po), shortening velocity (Vo),
      and power. The soleus had larger (P < 0.05) fibers (MHC I +18%; MHC IIa +19%),
      higher MHC I Vo (+13%), and higher MHC I Po (+18%) compared with fibers from the
      VL. In contrast, fibers from the VL had higher (P < 0.05) specific tension (MHC I
      +18%; MHC IIa +20%), and MHC I normalized power (+25%) compared with the soleus.
      There was a trend for MHC IIa soleus fibers to have higher Vo [MHC IIa +13% (P =
      0.058)], whereas VL MHC IIa fibers showed a trend for higher normalized power
      compared with soleus fibers [MHC IIa +33% (P = 0.079)]. No differences in
      absolute power were detected between muscles. These data highlight muscle
      specific differences in single-fiber contractile function that should serve as a
      scientific basis for consideration when extending observations of skeletal muscle
      tissue from one muscle of interest to other muscles of origin. This is important
      when examining skeletal muscle adaptation to physical states such as aging,
      unloading, and training.

PMID- 18815207
TI  - Insulin regulates hepatic leptin receptor expression in early lactating dairy
      cows.
AB  - Energy balance controls the expression of the leptin receptor (Lepr) in the
      ruminant hypothalamus but whether similar regulation occurs in peripheral tissues
      is unknown. To address this issue, we measured Lepr expression in the liver and
      adipose tissue of dairy cows during the transition from late pregnancy (LP) to
      early lactation (EL). This period is characterized by the development of a
      profound state of energy insufficiency and is associated with reduced plasma
      insulin and leptin and with increased plasma growth hormone. Hepatic expression
      of the short (Lepr-a) and long (Lepr-b) isoforms was 40% higher during EL (8 days
      postpartum) than LP (30 days prepartum). A similar effect was observed when
      negative energy balance was induced in nonpregnant, late-lactation dairy cows by
      food restriction, implicating energy insufficiency as a specific cause in EL. The
      stimulation of hepatic Lepr expression was reversed after a 48-h period of
      hyperinsulinemic euglycemia in EL. Changes in hepatic Lepr expression during
      chronic elevation of plasma leptin in EL or plasma growth hormone in nonpregnant,
      late-lactation cows did not support a role for these hormones in mediating the
      effects of energy insufficiency on hepatic Lepr expression. In adipose tissue,
      Lepr expression was increased 10-fold during the transition from LP to EL.
      Overall, these data indicate that hypoinsulinemia is partly responsible for the
      induction of Lepr expression in the liver, and perhaps adipose tissue, of energy
      deficient dairy cows.

PMID- 18815208
TI  - Rapid changes in glutamate levels in the posterior hypothalamus across sleep-wake
      states in freely behaving rats.
AB  - The histamine-containing posterior hypothalamic region (PH-TMN) plays a key role
      in sleep-wake regulation. We investigated rapid changes in glutamate release in
      the PH-TMN across the sleep-wake cycle with a glutamate biosensor that allows the
      measurement of glutamate levels at 1- to 4-s resolution. In the PH-TMN, glutamate
      levels increased in active waking (AW) and rapid eye movement (REM) sleep
      compared with quiet waking and nonrapid eye movement (NREM) sleep. There was a
      rapid (0.6 +/- 1.8 s) and progressive increase in glutamate levels at REM sleep
      onset. A reduction in glutamate levels consistently preceded the offset of REM
      sleep by 8 +/- 3 s. Short-duration sleep deprivation resulted in a progressive
      increase in glutamate levels in the PH-TMN, perifornical-lateral hypothalamus (PF
      LH), and cortex. We found that in the PF-LH, glutamate levels took a longer time
      to return to basal values compared with the time it took for glutamate levels to
      increase to peak values during AW onset. This is in contrast to other regions we
      studied in which the return to baseline values after AW was quicker than their
      rise with waking onset. In summary, we demonstrated an increase in glutamate
      levels in the PH-TMN with REM/AW onset and a drop in glutamate levels before the
      offset of REM. High temporal resolution measurement of glutamate levels reveals
      dynamic changes in release linked to the initiation and termination of REM sleep.

PMID- 18815209
TI  - Mechanisms mediating renal sympathetic activation to leptin in obesity.
AB  - Leptin plays a critical role in the control of energy homeostasis. The
      sympathetic cardiovascular actions of leptin have emerged as a potential link
      between obesity and hypertension. We previously demonstrated that in mice, modest
      obesity induced by 10 wk of a high-fat diet is associated with preservation of
      leptin ability to increase renal sympathetic nerve activity (SNA) despite the
      resistance to the metabolic effects of leptin. Here, we examined whether
      selective leptin resistance exists in mice with late-stage diet-induced obesity
      (DIO) produced by 20 wk of a high-fat diet. The decrease in food intake and body
      weight induced by intraperitoneal or intracerebroventricular injection of leptin
      was significantly attenuated in the DIO mice. Regional SNA responses to
      intravenous leptin were also attenuated in DIO mice. In contrast,
      intracerebroventricularly administered leptin caused contrasting effects on
      regional SNA in DIO mice. Renal SNA response to intracerebroventricular leptin
      was preserved, whereas lumbar and brown adipose tissue SNA responses were
      attenuated. Intact renal SNA response to leptin combined with the increased
      cerebrospinal fluid leptin levels in DIO mice represents a potential mechanism
      for the adverse cardiovascular consequences of obesity. Lastly, we examined the
      role of phosphoinositol-3 kinase (PI3K) and melanocortin receptors (MCR) in
      mediating the preserved renal SNA response to leptin in obesity. Presence of PI3K
      inhibitor (LY294002) or MC3/4R antagonist (SHU9119) significantly attenuated the
      renal SNA response to leptin in DIO and agouti obese mice. Our results
      demonstrate the importance of PI3K and melanocortin receptors in the transduction
      of leptin-induced renal sympathetic activation in obesity.

PMID- 18815210
TI  - Changes in brain mRNA levels of gonadotropin-releasing hormone, pituitary
      adenylate cyclase activating polypeptide, and somatostatin during ovulatory
      luteinizing hormone and growth hormone surges in goldfish.
AB  - In goldfish, circulating LH and growth hormone (GH) levels surge at the time of
      ovulation. In the present study, changes in gene expression of salmon
      gonadotropin-releasing hormone (sGnRH), chicken GnRH-II (cGnRH-II), somatostatin
      (SS) and pituitary adenylate cyclase activating polypeptide (PACAP) were analyzed
      during temperature- and spawning substrate-induced ovulation in goldfish. The
      results demonstrated that increases in PACAP gene expression during ovulation are
      best correlated with the GH secretion profile. These results suggest that PACAP,
      instead of GnRH, is involved in the control of GH secretion during ovulation.
      Increases of two of the SS transcripts during ovulation are interpreted as the
      activation of a negative feedback mechanism triggered by high GH levels. The
      results showed a differential regulation of sGnRH and cGnRH-II gene expression
      during ovulation, suggesting that sGnRH controls LH secretion, whereas cGnRH-II
      correlates best with spawning behavior. This conclusion is further supported by
      the finding that nonovulated fish induced to perform spawning behavior by
      prostaglandin F2alpha treatment increased cGnRH-II expression in both forebrain
      and midbrain, but decreased sGnRH expression in the forebrain.

PMID- 18815212
TI  - Comparison of TEM specimen preparation of perovskite thin films by tripod
      polishing and conventional ion milling.
AB  - In this article, the effects of the transmission electron microscopy (TEM)
      specimen preparation techniques, such as ion milling and tripod polishing on
      perovskite oxides for high-resolution TEM investigation, are compared.
      Conventional and liquid nitrogen cooled ion milling induce a new domain
      orientation in thin films of SrRuO(3) and LaFeO(3) grown on (001)-oriented
      SrTiO(3) substrates. This is not observed in tripod-polished specimens. Different
      ion milling rates for thin films and substrates in cross-section specimens lead
      to artefacts in the interface region, degrading the specimen quality. This is
      illustrated by SrRuO(3) and PbTiO(3) thin films grown on (001)-oriented SrTiO(3).
      By applying tripod polishing and gentle low-angle, low-energy ion milling while
      cooling the sample, the effects from specimen preparation are reduced resulting
      in higher quality of the TEM study. In the process of making face-to-face cross
      section specimens by tripod polishing, it is crucial that the glue layer
      attaching the slabs of material is very thin (<50 nm).

PMID- 18815211
TI  - Nitric oxide modulates the cardiovascular effects elicited by acetylcholine in
      the NTS of awake rats.
AB  - Microinjection of acetylcholine chloride (ACh) in the nucleus of the solitary
      tract (NTS) of awake rats caused a transient and dose-dependent hypotension and
      bradycardia. Because it is known that cardiovascular reflexes are affected by
      nitric oxide (NO) produced in the NTS, we investigated whether these ACh-induced
      responses depend on NO in the NTS. Responses to ACh (500 pmol in 100 nl) were
      strongly reduced by ipsilateral microinjection of the NOS inhibitor NG-nitro-L
      arginine methyl ester (L-NAME; 10 nmol in 100 nl) in the NTS: mean arterial
      pressure (MAP) fell by 50 +/- 5 mmHg before L-NAME to 9 +/- 4 mmHg, 10 min after
      L-NAME, and HR fell by 100 +/- 26 bpm before L-NAME to 20 +/- 10 bpm, 10 min
      after L-NAME (both P < 0.05). Microinjection of the selective inhibitor of
      neuronal nitric oxide synthase (nNOS), 1-(2-trifluoromethylphenyl) imidazole
      (TRIM; 13.3 nmol in 100 nl), in the NTS also reduced responses to ACh: MAP fell
      from 42 +/- 3 mmHg before TRIM to 27 +/- 6 mmHg, 10 min after TRIM (P < 0.05).
      TRIM also tended to reduce ACh-induced bradycardia, but this effect was not
      statistically significant. ACh-induced hypotension and bradycardia returned to
      control levels 30-45 min after NOS inhibition. Control injections with D-NAME and
      saline did not affect resting values or the response to ACh. In conclusion,
      injection of ACh into the NTS of conscious rats induces hypotension and
      bradycardia, and these effects may be mediated at least partly by NO produced in
      NTS neurons.

PMID- 18815213
TI  - Inhibitors of GlyT1 affect glycine transport via discrete binding sites.
AB  - In the forebrain, synaptic glycine concentrations are regulated through the
      glycine transporter GlyT1. Because glycine is a coagonist of the N-methyl-D
      aspartate (NMDA) receptor (NMDAR), which has been implicated in schizophrenia,
      inhibition of GlyT1 is thought to provide an option for the treatment of
      schizophrenia. In support of this hypothesis, GlyT1 inhibitors facilitate in vivo
      NMDAR function and demonstrate antipsychotic-like effects in animal models. Among
      the specific GlyT1 inhibitors, substituted N-methyl-glycine (sarcosine)
      derivatives (e.g., (R)-N[3-(4'fluorophenyl)-3-(4'phenyl-phenoxy)propyl]-sarcosine
      [NFPS], (R)-N[3-phenyl-3-(4'-(4-toluoyl)phenoxy)-propyl]sarcosine [(R)-NPTS], and
      (R,S)-(+/-)N-methyl-N-[(4-trifluoromethyl)phenoxy]-3-phenyl-propylglycine
      [Org24589]), and non-sarcosine-containing inhibitors, such as 2-chloro-N-[(S)
      phenyl[(2S)-piperidin-2-yl] methyl]-3-trifluoromethyl benzamide,
      monohydrochloride (SSR504734), have been described. In the present study, we
      analyzed the mode of interaction of these compounds with GlyT1 by using
      electrophysiological measurements in Xenopus laevis oocytes, and with two binding
      assays, using [(3)H](R)-NPTS or 2-chloro-N-[(S)-phenyl[(2S)-N-methylpiperidin-2
      yl]-methyl]-3-trifluoromethyl benzamide monohydrochloride ([(3)H]N-methyl
      SSR504734) as radioligands. Inhibition of electrogenic glycine transport by
      sarcosine-based compounds was apparently irreversible and independent of glycine
      concentration. The latter indicates a noncompetitive mode of action. In contrast,
      both SSR504734 and N-methyl-SSR504734 exhibited reversible and competitive
      inhibition of glycine transport. In GlyT1-expressing membranes, the binding of
      the novel radioligand [(3)H]N-methyl-SSR504734 to a single site on GlyT1 was
      competitively displaced by glycine and SSR504734 but noncompetitively by
      sarcosine-based compounds. Inversely, [(3)H](R)-NPTS binding was competitively
      inhibited by sarcosine-based compounds, whereas glycine, SSR504734, and N-methyl
      SSR504734 noncompetitively decreased maximal binding. Our data indicate that
      besides exerting an apparently irreversible or reversible inhibition, GlyT1
      inhibitors differ by exhibiting either a noncompetitive or competitive mode of
      inhibition. The divergent modes of inhibition may significantly affect the
      efficacy and tolerability of these drugs.

PMID- 18815214
TI  - Mechanisms of myocyte cytotoxicity induced by the multiple receptor tyrosine
      kinase inhibitor sunitinib.
AB  - The anticancer tyrosine kinase inhibitor sunitinib has been shown recently to be
      cardiotoxic. Using a neonatal rat myocyte model, we investigated various
      mechanisms that might be responsible for its cardiotoxicity. Sunitinib potently
      inhibited the enzyme activity of both AMP-activated protein kinase (AMPK) and the
      ribosomal S6 kinase RSK1 at therapeutically relevant concentrations. Heart tissue
      with its high energy needs might be particularly sensitive to inhibition of AMPK
      because of its role as an energy sensor regulating ATP levels. As measured by
      lactate dehydrogenase release, sunitinib treatment of myocytes caused dose
      dependent damage at therapeutic levels. Sunitinib treatment also caused a dose
      dependent reduction in myocyte protein levels of the phosphorylated alpha and
      beta isoforms of the AMPK phosphorylation target acetyl-Coenzyme A carboxylase.
      However, myocytes were not protected from sunitinib treatment by pretreating them
      with the AMPK-activating antidiabetic drug metformin. Sunitinib treatment of
      myocytes also did not affect cellular ATP levels. Together, these last two
      results do not suggest a major role for inhibition of AMPK in sunitinib-induced
      myocyte damage. Dexrazoxane, which is a clinically approved doxorubicin
      cardioprotective agent, also did not protect myocytes from damage, which suggests
      that sunitinib did not induce oxidative damage. In conclusion, even though
      sunitinib potently inhibits AMPK and RSK1, given the extreme lack of kinase
      selectivity that sunitinib exhibits, it is likely that inhibition of other
      kinases or combinations of kinases are responsible for the cardiotoxic effects of
      sunitinib.

PMID- 18815215
TI  - The selective Alzheimer's disease indicator-1 gene (Seladin-1/DHCR24) is a liver
      X receptor target gene.
AB  - The nuclear hormone receptors liver X receptor alpha (LXRalpha) and LXRbeta
      function as physiological receptors for oxidized cholesterol metabolites
      (oxysterols) and regulate several aspects of cholesterol and lipid metabolism.
      Seladin-1 was originally identified as a gene whose expression was down-regulated
      in regions of the brain associated with Alzheimer's disease. Seladin-1 has been
      demonstrated to be neuroprotective and was later characterized as 3beta
      hydroxysterol-Delta24 reductase (DHCR24), a key enzyme in the cholesterologenic
      pathway. Seladin-1 has also been shown to regulate lipid raft formation. In a
      whole genome screen for direct LXRalpha target genes, we identified an LXRalpha
      occupancy site within the second intron of the Seladin-1/DHCR24 gene. We
      characterized a novel LXR response element within the second intron of this gene
      that is able to confer LXR-specific ligand responsiveness to reporter gene in
      both HepG2 and human embryonic kidney 293 cells. Furthermore, we found that
      Seladin-1/DHCR24 gene expression is significantly decreased in skin isolated from
      LXRbeta-null mice. Our data suggest that Seladin-1/DHCR24 is an LXR target gene
      and that LXR may regulate lipid raft formation.

PMID- 18815216
TI  - Renoprotective mechanisms of soy protein intake in the obese Zucker rat.
AB  - We previously showed that long-term consumption of a soy protein diet (SoyP)
      reduces renal damage in obese Zucker (ObeseZ) rats by restoring urinary NO2 and
      NO3 excretion (UNO2/NO3V), suggesting that nitric oxide (NO) deficiency may
      contribute to the renal progression observed in this model. In addition, there is
      compelling evidence that hyperleptinemia produced deleterious effects on the
      kidney through its interaction with the short leptin receptor (ObRa). This study
      was designed to evaluate the contribution of the NO/endothelial NO synthase
      (eNOS) system, renal oxidative stress, and ObRa expression to the renoprotection
      conferred by the consumption of a SoyP in ObeseZ rats. Ten lean and ten male
      ObeseZ rats were included. One-half of each group was fed with a 20% SoyP and the
      other half with a 20% casein protein diet (CasP) over the course of 160 days.
      eNOS protein levels and phosphorylation, renal lipoperoxidation (rLPO), and
      antioxidant enzyme activity were assessed. In addition, renal ObRa, TGF-beta, and
      kidney injury molecule (Kim-1) mRNA levels, as well as urinary Kim-1 levels, were
      measured. Renal injury observed in ObeseZ rats fed with CasP was not associated
      with changes in eNOS expression or phosphorylation. However, this group did
      present with increased rLPO, reduced catalase activity, and upregulation of ObRa,
      TGF-beta1, and Kim-1. In contrast, ObeseZ rats fed with a SoyP exhibited a
      reduction in NOS-Thr495 phosphorylation and rLPO, as well as an enhanced catalase
      activity. These findings were associated with a significant reduction of ObRa,
      TGF-beta1, and Kim-1 mRNA levels and urinary Kim-1 protein. Our results show that
      renoprotection by SoyP in ObeseZ rats is in part mediated by increased NO
      availability secondary to a reduction in eNOS-T495 phosphorylation and oxidative
      stress, together with a significant reduction in ObRa and TGF-beta expression.

PMID- 18815217
TI  - Urothelial expression of neuropilins and VEGF receptors in control and
      interstitial cystitis patients.
AB  - Interstitial cystitis (IC) is a chronic and painful bladder syndrome of unknown
      cause with no reliable biological marker or effective therapy. Vascular
      endothelial growth factor (VEGF), which plays a key role in bladder inflammation,
      is closely associated with the vascular alterations observed in patients with IC.
      However, our recent findings of VEGF receptors (VEGF-Rs) and VEGF coreceptors on
      nonendothelial cells in human and mouse urothelium suggest that additional VEGF
      targets and functions are possible in IC bladders. We report here that VEGF-Rs
      and coreceptors (neuropilins; NRP) are strongly expressed in both the human
      bladder urothelium and in the human bladder cancer cell line (J82) and that the
      expression of NRP2 and VEGF-R1 is significantly downregulated in IC compared with
      control subjects. In addition, treatment of J82 cells with bacillus Calmette
      Guerin (BCG), a novel treatment strategy for IC, upregulates the messages for
      NRPs and VEGF-Rs. Furthermore, intravesical instillation of an internalizable
      VEGF fluorescent tracer (scVEGF/Cy5.5) into mouse urinary bladders results in a
      marked ligand accumulation in the urothelium and bladder parenchyma, indicating
      that urothelial VEGF-Rs are functionally active and capable of ligand interaction
      and internalization. Our results suggest that the VEGF pathway is altered in IC,
      that urinary VEGF may gain access to the bladder wall via these receptors, and
      that BCG treatment may replenish the missing VEGF-Rs/NRP receptors. Together,
      these results suggest that levels of NRPs, VEGF-Rs, and VEGF are new putative
      markers for the diagnosis of IC and that modulating these receptors can be
      exploited as therapeutic strategies.

PMID- 18815218
TI  - JAK2/Y343/STAT5 signaling axis is required for erythropoietin-mediated protection
      against ischemic injury in primary renal tubular epithelial cells.
AB  - Erythropoietin has emerged as a potential therapy for the treatment of ischemic
      tissue injury. In erythroid cells, the JAK2/Y343/STAT5 signaling axis has been
      shown to be necessary for stress but not steady-state erythropoiesis. The
      requirement for STAT5 activation in erythropoietin-mediated protection from
      ischemic injury has not been well-studied. To answer this question, we induced
      reproducible necrotic ischemic injury in primary mouse renal tubular epithelial
      cells (RTEC) in vitro. Using RTEC from erythropoietin receptor mutant mice with
      differential STAT5 signaling capabilities, we demonstrated first, that EPO
      administration either before or during injury significantly protects against mild
      moderate but not severe necrotic cell death; and second, the JAK2/Y343/STAT5
      signaling axis is required for protection against ischemic injury in primary
      mouse RTEC. In addition, we identified Pim-3, a prosurvival STAT5 target gene, as
      responsive to EPO in the noninjured kidney both in vitro and in vivo.

PMID- 18815219
TI  - p53 regulates renal expression of HIF-1{alpha} and pVHL under physiological
      conditions and after ischemia-reperfusion injury.
AB  - Ischemia-reperfusion injury (IRI) is a common cause of acute kidney injury (AKI)
      and is characterized by widespread tubular and microvascular damage. The tumor
      suppressor p53 is upregulated after IRI and contributes to renal injury in part
      by promoting apoptosis. Acute, short-term inhibition of p53 with pifithrin-alpha
      conveys significant protection after IRI. The hypoxia-inducible factor-1 (HIF-1)
      pathway is also activated after IRI and has opposing effects to those promoted by
      p53. The balance between the HIF-1 and p53 responses can determine the outcome of
      IRI. In this manuscript, we investigate whether p53 regulates the HIF-1 pathway
      in a rodent model of IRI. HIF-1alpha is principally expressed in the collecting
      tubules (CT) and thick ascending limbs (TAL) under physiological conditions.
      However, inhibition of p53 with pifithrin-alpha increases the faint expression of
      HIF-1alpha in proximal tubules (PT) under physiological conditions. Twenty-four
      hours after IRI, HIF-1alpha expression is decreased in both CT and TAL. HIF
      1alpha expression in the PT is not significantly altered after IRI. Acute
      inhibition of p53 significantly increases HIF-1alpha expression in the PT after
      IRI. Additionally, pifithrin-alpha prevents the IRI-induced decrease in HIF
      1alpha in the CT and TAL. Parallel changes are observed in the HIF-1alpha
      transcriptive target, carbonic anhydrase-9. Finally, inhibition of p53 prevents
      the dramatic changes in Von Hippel-Lindau protein morphology and expression after
      IRI. We conclude that activation of p53 after IRI mitigates the concomitant
      activation of the protective HIF-1 pathway. Modulating the interactions between
      the p53 and HIF-1 pathway can provide novel options in the treatment of AKI.

PMID- 18815220
TI  - Lipocalin-2-induced renal regeneration depends on cytokines.
AB  - This study investigated whether the renal regeneration occurring in the recovery
      phase of kidney ischemia-reperfusion (I/R) is mediated by endogenously generated
      lipocalin-2 (Lcn2). A second objective was to examine whether Lcn2-mediated cell
      effects could be regulated by the inflammatory cytokines in the environment
      through their action on Lcn2 receptors (Lcn2R and megalin). Male Swiss mice were
      subjected to 30 min of renal ischemia with a reperfusion period of 24 h (early
      reperfusion, expected time for maximum inflammation) and 96 h (late reperfusion,
      expected time for maximum regeneration). Different experimental groups underwent
      I/R, I/R with iv anti-mouse Lcn2 monoclonal antibody injected during the
      early/inflammatory or late/recovery phase, and I/R with proinflammatory cytokine
      cocktail administration (recombinant mouse IL-1beta, TNF-alpha, and IFN-gamma).
      Compared with control nonischemic mice, the expression of three proliferation
      markers (stathmin, PCNA, and Ki-67, analyzed by quantitative RT-PCR) increased
      significantly in the I/R-treated animals. Blockade of Lcn2 by addition of anti
      Lcn2 antibody significantly decreased the expression of these three proliferation
      markers when administered in the late/reparative phase, but had the opposite
      effect when administered in the early/inflammatory phase. Proinflammatory
      cytokine cocktail administration reduced the proliferative effects of Lcn2, and
      repressed Lcn2R and megalin expression. In conclusion, endogenously generated
      Lcn2 induces renal cell regeneration depending on the inflammatory cytokines in
      kidney I/R.

PMID- 18815221
TI  - High glucose activates PKC-zeta and NADPH oxidase through autocrine TGF-beta1
      signaling in mesangial cells.
AB  - Conversion of normally quiescent mesangial cells into extracellular matrix
      overproducing myofibroblasts in response to high ambient glucose and transforming
      growth factor (TGF)-beta(1) is central to the pathogenesis of diabetic
      nephropathy. Previously, we reported that mesangial cells respond to high glucose
      by generating reactive oxygen species (ROS) from NADPH oxidase dependent on
      protein kinase C (PKC) -zeta activation. We investigated the role of TGF-beta(1)
      in this action of high glucose on primary rat mesangial cells within 1-48 h. Both
      high glucose and exogenous TGF-beta(1) stimulated PKC-zeta kinase activity, as
      measured by an immune complex kinase assay and immunofluorescence confocal
      cellular imaging. In high glucose, Akt Ser473 phosphorylation appeared within 1 h
      and Smad2/3 nuclear translocation was prevented with neutralizing TGF-beta(1)
      antibodies. Neutralizing TGF-beta(1) antibodies, or a TGF-beta receptor kinase
      inhibitor (LY364947), or a phosphatidylinositol 3,4,5-trisphosphate (PI3) kinase
      inhibitor (wortmannin), prevented PKC-zeta activation by high glucose. TGF
      beta(1) also stimulated cellular membrane translocation of PKC-alpha, -beta(1), 
      delta, and -epsilon, similar to high glucose. High glucose and TGF-beta(1)
      enhanced ROS generation by mesangial cell NADPH oxidase, as detected by 2,7
      dichlorofluorescein immunofluorescence. This response was abrogated by
      neutralizing TGF-beta(1) antibodies, LY364947, or a specific PKC-zeta
      pseudosubstrate peptide inhibitor. Expression of constitutively active PKC-zeta
      in normal glucose caused upregulation of p22(phox), a likely mechanism of NADPH
      oxidase activation. We conclude that very early responses of mesangial cells to
      high glucose include autocrine TGF-beta(1) stimulation of PKC isozymes including
      PI3 kinase activation of PKC-zeta and consequent generation of ROS by NADPH
      oxidase.

PMID- 18815222
TI  - Impact of overexpression of metallothionein-1 on cell cycle progression and zinc
      toxicity.
AB  - Metallothioneins (MTs) have an important role in zinc homeostasis and may
      counteract the impact of oversupply. Both intracellular zinc and MT expression
      have been implicated in proliferation control and resistance to cellular stress,
      although the interdependency is unclear. The study addresses the consequences of
      a steady-state overexpression of MT-1 for intracellular zinc levels, cell cycle
      progression, and protection from zinc toxicity using a panel of cell lines with
      differential expression of MT-1. The panel comprised parental Chinese hamster
      ovary-K1 cells with low endogenous expression of MT and transfectants with
      enhanced expression of mouse MT-1 on an autonomously replicating expression
      vector with a noninducible promoter. Cell cycle progression, determined by flow
      cytometry and time-lapse microscopy, revealed that enhanced cytoplasmic
      expression of MT-1 does not impact on normal cell cycle operation, suggesting
      that basal levels of MT-1 expression are not limiting for background levels of
      oxidative stress. MT-1 overexpression correlated with a steady-state increase in
      cytoplasmic free Zn(2+), assessed using the fluorescent zinc-sensor Zinquin,
      particularly at high levels of overexpression, further suggesting that zinc
      availability is normally not limiting for cell cycle progression. Enhanced MT-1
      expression, over a 10-fold range, had a clear impact on resistance to Cd(2+) and
      Zn(2+) toxicity. In the case of Zn(2+), the degree of protection afforded was
      less, indicating that MT-1 has a limited range and saturable capacity for
      effecting resistance. The results have implications for the use of cellular
      stress responses to exogenously supplied zinc and zinc-based systemic therapies.

PMID- 18815223
TI  - The monomeric G proteins AGS1 and Rhes selectively influence Galphai-dependent
      signaling to modulate N-type (CaV2.2) calcium channels.
AB  - Activator of G protein Signaling 1 (AGS1) and Ras homologue enriched in striatum
      (Rhes) define a new group of Ras-like monomeric G proteins whose signaling
      properties and physiological roles are just beginning to be understood. Previous
      results suggest that AGS1 and Rhes exhibit distinct preferences for
      heterotrimeric G proteins, with AGS1 selectively influencing Galphai and Rhes
      selectively influencing Galphas. Here, we demonstrate that AGS1 and Rhes trigger
      nearly identical modulation of N-type Ca(2+) channels (Ca(V)2.2) by selectively
      altering Galphai-dependent signaling. Whole-cell currents were recorded from
      HEK293 cells expressing Ca(V)2.2 and Galphai- or Galphas-coupled receptors. AGS1
      and Rhes reduced basal current densities and triggered tonic voltage-dependent
      (VD) inhibition of Ca(V)2.2. Additionally, each protein attenuated agonist
      initiated channel inhibition through Galphai-coupled receptors without reducing
      channel inhibition through a Galphas-coupled receptor. The above effects of AGS1
      and Rhes were blocked by pertussis toxin (PTX) or by expression of a Gbetagamma
      sequestering peptide (masGRK3ct). Transfection with HRas, KRas2, Rap1A-G12V,
      Rap2B, Rheb2, or Gem failed to duplicate the effects of AGS1 and Rhes on
      Ca(V)2.2. Our data provide the first demonstration that AGS1 and Rhes exhibit
      similar if not identical signaling properties since both trigger tonic Gbetagamma
      signaling and both attenuate receptor-initiated signaling by the Gbetagamma
      subunits of PTX-sensitive G proteins. These results are consistent with the
      possibility that AGS1 and Rhes modulate Ca(2+) influx through Ca(V)2.2 channels
      under more physiological conditions and thereby influence Ca(2+)-dependent events
      such as neurosecretion.

PMID- 18815224
TI  - Anisotropic diffusion of fluorescently labeled ATP in rat cardiomyocytes
      determined by raster image correlation spectroscopy.
AB  - A series of experimental data points to the existence of profound diffusion
      restrictions of ADP/ATP in rat cardiomyocytes. This assumption is required to
      explain the measurements of kinetics of respiration, sarcoplasmic reticulum
      loading with calcium, and kinetics of ATP-sensitive potassium channels. To be
      able to analyze and estimate the role of intracellular diffusion restrictions on
      bioenergetics, the intracellular diffusion coefficients of metabolites have to be
      determined. The aim of this work was to develop a practical method for
      determining diffusion coefficients in anisotropic medium and to estimate the
      overall diffusion coefficients of fluorescently labeled ATP in rat
      cardiomyocytes. For that, we have extended raster image correlation spectroscopy
      (RICS) protocols to be able to discriminate the anisotropy in the diffusion
      coefficient tensor. Using this extended protocol, we estimated diffusion
      coefficients of ATP labeled with the fluorescent conjugate Alexa Fluor 647 (Alexa
      ATP). In the analysis, we assumed that the diffusion tensor can be described by
      two values: diffusion coefficient along the myofibril and that across it. The
      average diffusion coefficients found for Alexa-ATP were as follows: 83 +/- 14
      microm(2)/s in the longitudinal and 52 +/- 16 microm(2)/s in the transverse
      directions (n = 8, mean +/- SD). Those values are approximately 2 (longitudinal)
      and approximately 3.5 (transverse) times smaller than the diffusion coefficient
      value estimated for the surrounding solution. Such uneven reduction of average
      diffusion coefficient leads to anisotropic diffusion in rat cardiomyocytes.
      Although the source for such anisotropy is uncertain, we speculate that it may be
      induced by the ordered pattern of intracellular structures in rat cardiomyocytes.

PMID- 18815225
TI  - The use of BeWo cells as an in vitro model for placental iron transport.
AB  - BeWo cells are a placental cell line that has been widely used as an in vitro
      model for the placenta. The b30 subclone of these cells can be grown on permeable
      membranes in bicameral chambers to form confluent cell layers, enabling rates of
      both nutrient uptake into the cells from the apical surface and efflux from the
      basolateral membrane to be determined. The aim of this study was to evaluate
      structural and functional properties of confluent b30 BeWo cell layers grown in
      bicameral chambers, focusing on the potential application for studying receptor
      mediated uptake and transport of transferrin (Tf)-bound iron (Fe-Tf). While it
      proved extremely difficult to establish and maintain an intact BeWo cell
      monolayer, it was possible to grow the cells to a confluent multilayer. Iron,
      applied as Fe-Tf, was rapidly transported across this cell layer; 9.3 +/- 0.5% of
      the total dose was transported after 8 h, equivalent to 38.8 +/- 2.1 pmol.cm(
      2).h(-1). Transfer of Tf across the cell layer was much more limited; 2.4 +/-
      0.2% of the total dose was transported after 8 h, equivalent to 5.0 +/- 0.4
      pmol.cm(-2).h(-1). Compartmental modeling of these data suggested that iron was
      transported across the cell layer predominantly, if not exclusively, via a
      transcellular route, whereas Tf taken up into the cells was predominantly
      recycled back to the apical compartment. The results suggest that these cells are
      very efficient at transporting iron and, under carefully controlled conditions,
      can be a valuable tool for the study of iron transport in the placenta.

PMID- 18815226
TI  - Regulation of cell proliferation by intermediate-conductance Ca2+-activated
      potassium and volume-sensitive chloride channels in mouse mesenchymal stem cells.
AB  - Bone marrow mesenchymal stem cells (MSCs) are a promising cell source for
      regenerative medicine; however, their cellular physiology is not fully
      understood. The present study aimed at exploring the potential roles of the two
      dominant functional ion channels, intermediate-conductance Ca(2+)-activated
      potassium (IK(Ca)) and volume-sensitive chloride (I(Cl.vol)) channels, in
      regulating proliferation of mouse MSCs. We found that inhibition of IK(Ca) with
      clotrimazole and I(Cl.vol) with 5-nitro-1-(3-phenylpropylamino) benzoic acid
      (NPPB) reduced cell proliferation in a concentration-dependent manner. Knockdown
      of KCa3.1 or Clcn3 with specific short interference (si)RNAs significantly
      reduced IK(Ca) or I(Cl.vol) density and channel protein and produced a remarkable
      suppression of cell proliferation (by 24.4 +/- 9.6% and 29.5 +/- 7.2%,
      respectively, P < 0.05 vs. controls). Flow cytometry analysis showed that mouse
      MSCs retained at G(0)/G(1) phase (control: 51.65 +/- 3.43%) by inhibiting IK(Ca)
      or I(Cl.vol) using clotrimazole (2 microM: 64.45 +/- 2.20%, P < 0.05) or NPPB
      (200 microM: 82.89 +/- 2.49%, P < 0.05) or the specific siRNAs, meanwhile
      distribution of cells in S phase was decreased. Western blot analysis revealed a
      reduced expression of the cell cycle regulatory proteins cyclin D1 and cyclin E.
      Collectively, our results have demonstrated that IK(Ca) and I(Cl.vol) channels
      regulate cell cycle progression and proliferation of mouse MSCs by modulating
      cyclin D1 and cyclin E expression.

PMID- 18815227
TI  - Ammonia excretion by the skin of zebrafish (Danio rerio) larvae.
AB  - The mechanism of ammonia excretion in freshwater teleosts is not well understood.
      In this study, scanning ion-selective electrode technique was applied to measure
      H(+) and NH(4)(+) fluxes in specific cells on the skin of zebrafish larvae.
      NH(4)(+) extrusion was relatively high in H(+) pump-rich cells, which were
      identified as the H(+)-secreting ionocyte in zebrafish. Minor NH(4)(+) extrusion
      was also detected in keratinocytes and other types of ionocytes in larval skin.
      NH(4)(+) extrusion from the skin was tightly linked to acid secretion. Increases
      in the external pH and buffer concentration (5 mM MOPS) diminished H(+) and
      NH(4)(+) gradients at the larval surface. Moreover, coupled decreases in NH(4)(+)
      and H(+) extrusion were found in larvae treated with an H(+)-pump inhibitor
      (bafilomycin A1) or H(+)-pump gene (atp6v1a) knockdown. Knockdown of Rhcg1 with
      morpholino-oligonucleotides also decreased NH(4)(+) excretion. This study
      demonstrates ammonia excretion in epithelial cells of larval skin through an acid
      trapping mechanism, and it provides direct evidence for the involvement of the
      H(+) pump and an Rh glycoprotein (Rhcg1) in ammonia excretion.

PMID- 18815228
TI  - Essential role of EP3 subtype in prostaglandin E2-induced adhesion of mouse
      cultured and peritoneal mast cells to the Arg-Gly-Asp-enriched matrix.
AB  - Accumulating evidence has indicated that mast cells can modulate a wide variety
      of immune responses. Migration and adhesion play a critical role in regulation of
      tissue mast cell function, in particular, under inflammatory conditions. We
      previously demonstrated that prostaglandin (PG) E(2) stimulates adhesion of a
      mouse mastocytoma cell line, P-815, to the Arg-Gly-Asp (RGD)-enriched matrix
      through cooperation between two PGE(2) receptor subtypes: EP3 and EP4 (Hatae N,
      Kita A, Tanaka S, Sugimoto Y, Ichikawa A. J Biol Chem 278: 17977-17981, 2003). We
      here investigated PGE(2)-induced adhesion of IL-3-dependent bone marrow-derived
      cultured mast cells (BMMCs). In contrast to the elevated cAMP-dependent adhesion
      of P-815 cells, EP3-mediated Ca(2+) mobilization plays a pivotal role in PGE(2)
      induced adhesion of BMMCs. Adhesion and Ca(2+) mobilization induced by PGE(2)
      were abolished in the Ptger3(-/-) BMMCs and were significantly suppressed by
      treatment with pertussis toxin, a phospholipase C inhibitor, U-73122, and a store
      operated Ca(2+) channel inhibitor, SKF 36965, indicating the involvement of G(i)
      mediated Ca(2+) influx. We then investigated PGE(2)-induced adhesion of
      peritoneal mast cells to the RGD-enriched matrix. EP3 subtype was found to be the
      dominant PGE receptor that expresses in mouse peritoneal mast cells. PGE(2)
      induced adhesion of the peritoneal mast cells of the Ptger3(+/+) mice, but not
      that of the Ptger3(-/-) mice. In rat peritoneal mast cells, PGE(2) or an EP3
      agonist stimulated both Ca(2+) mobilization and adhesion to the RGD-enriched
      matrix. These results suggested that the EP3 subtype plays a pivotal role in
      PGE(2)-induced adhesion of murine mast cells to the RGD-enriched matrix through
      Ca(2+) mobilization.

PMID- 18815229
TI  - Electrogenic NBCe1 (SLC4A4), but not electroneutral NBCn1 (SLC4A7), cotransporter
      undergoes cholinergic-stimulated endocytosis in salivary ParC5 cells.
AB  - Cholinergic agonists are major stimuli for fluid secretion in parotid acinar
      cells. Saliva bicarbonate is essential for maintaining oral health. Electrogenic
      and electroneutral Na(+)-HCO(3)(-) cotransporters (NBCe1 and NBCn1) are abundant
      in parotid glands. We previously reported that angiotensin regulates NBCe1 by
      endocytosis in Xenopus oocytes. Here, we studied cholinergic regulation of NBCe1
      and NBCn1 membrane trafficking by confocal fluorescent microscopy and surface
      biotinylation in parotid epithelial cells. NBCe1 and NBCn1 colocalized with E
      cadherin monoclonal antibody at the basolateral membrane (BLM) in polarized ParC5
      cells. Inhibition of constitutive recycling with the carboxylic ionophore
      monensin or the calmodulin antagonist W-13 caused NBCe1 to accumulate in early
      endosomes with a parallel loss from the BLM, suggesting that NBCe1 is
      constitutively endocytosed. Carbachol and PMA likewise caused redistribution of
      NBCe1 from BLM to early endosomes. The PKC inhibitor, GF-109203X, blocked this
      redistribution, indicating a role for PKC. In contrast, BLM NBCn1 was not
      downregulated in parotid acinar cells treated with constitutive recycling
      inhibitors, cholinergic stimulators, or PMA. We likewise demonstrate striking
      differences in regulation of membrane trafficking of NBCe1 vs. NBCn1 in resting
      and stimulated cells. We speculate that endocytosis of NBCe1, which coincides
      with the transition to a steady-state phase of stimulated fluid secretion, could
      be a part of acinar cell adjustment to a continuous secretory response. Stable
      association of NBCn1 at the membrane may facilitate constitutive uptake of
      HCO(3)(-) across the BLM, thus supporting HCO(3)(-) luminal secretion and/or
      maintaining acid-base homeostasis in stimulated cells.

PMID- 18815230
TI  - Human neutrophil surface protrusion under a point load: location independence and
      viscoelasticity.
AB  - Mechanical properties of neutrophils have been recognized as key contributors to
      stabilizing neutrophil rolling on the endothelium during the inflammatory
      response. In particular, accumulating evidence suggests that surface protrusion
      and tether extraction from neutrophils facilitate stable rolling by relieving the
      disruptive forces on adhesive bonds. Using a customized optical trap setup, we
      applied piconewton-level pulling forces on targeted receptors that were located
      either on the microvillus tip (CD162) or intermicrovillus surface of neutrophils
      (CD18 and CD44). Under a constant force-loading rate, there always occurred an
      initial tent-like surface protrusion that was terminated either by rupture of the
      adhesion or by a "yield" or "crossover" to tether extraction. The corresponding
      protrusional stiffness of neutrophils was found to be between 0.06 and 0.11
      pN/nm, depending on the force-loading rate and the cytoskeletal integrity, but
      not on the force location, the medium osmolality, nor the temperature increase
      from 22 degrees C to 37 degrees C. More importantly, we found that neutrophil
      surface protrusion was accompanied by force relaxation and hysteresis. In
      addition, the crossover force did not change much in the range of force-loading
      rates studied, and the protrusional stiffness of lymphocytes was similar to that
      of neutrophils. These results show that neutrophil surface protrusion is
      essentially viscoelastic, with a protrusional stiffness that stems primarily from
      the actin cortex, and the crossover force is independent of the receptor
      cytoskeleton interaction.

PMID- 18815231
TI  - Exposure of cord blood to Mycobacterium bovis BCG induces an innate response but
      not a T-cell cytokine response.
AB  - Despite routine vaccination with Mycobacterium bovis bacillus Calmette-Guerin
      (BCG) soon after birth, tuberculosis in babies and adults remains epidemic in
      South Africa. The immune responses of the naive newborn child and how they are
      affected by vaccination with BCG are as yet not fully understood. Immunity during
      pregnancy and in healthy human newborns may be skewed toward type 2 cytokine
      production; however, it is type 1 cytokines that are required for protection
      against M. tuberculosis infection. To better understand neonatal cytokine
      responses prior to and following exposure to mycobacteria, we have collected cord
      blood and peripheral blood samples and evaluated the cytokine response following
      ex vivo incubation with BCG. Gamma interferon (IFN-gamma), interleukin 10 (IL
      10), IL-12, and low levels of IL-13 and IL-5 but no IL-4 were secreted into the
      culture supernatant of cord blood mononuclear cells. Intracellular staining
      showed that IL-10 and IL-12 were produced by monocytes and that IFN-gamma was
      produced by natural killer (NK) cells but not by CD4(+) or CD8(+) T cells. In
      contrast, in the peripheral blood samples collected from babies 13 weeks post-BCG
      vaccination, IFN-gamma was detected within CD4(+) and CD8(+) cells. Taken
      together, the data suggest a central role for Th1 cytokines in naive as well as
      BCG-vaccinated neonates in the protective immune response to tuberculosis. NK
      cell-derived IFN-gamma produced in naive neonates likely plays a key protective
      role via monocyte activation and the priming of a subsequent adaptive Th1
      response.

PMID- 18815232
TI  - Kinetics of decline of maternal measles virus-neutralizing antibodies in sera of
      infants in France in 2006.
AB  - The optimal age for measles vaccination is an important health issue, since
      maternal antibodies may neutralize the vaccine antigen before a specific immune
      response develops, while delaying vaccination may increase the risk of
      complicated diseases in infants. However, measles vaccination impacts the
      duration of protection afforded by transplacental transfer of maternal
      antibodies: vaccination-induced maternal antibodies disappear faster than disease
      induced antibodies. In order to maintain protection against measles in infants,
      it is important to monitor the dynamics of this phenomenon in vaccinated
      populations. To assess the current situation in France, a multicenter,
      prospective seroepidemiological study was conducted in seven French hospitals
      between October 2005 and January 2007. Maternal measles antibody concentrations
      from 348 infants 0 to 15 months old were measured using the plaque reduction
      neutralization assay. Geometric mean concentrations and the percentage of infants
      with maternal measles antibody concentrations above the protection threshold
      (>or=120 mIU/ml) were assessed according to age. Results show that after more
      than 20 years of routine measles vaccination in France, maternal measles
      neutralizing antibodies decrease dramatically in French infants by 6 months of
      age, from 1,740 mIU/ml for infants 0 to 1 month old to 223 mIU/ml for infants 5
      to 6 months old, and that 90% of infants are not protected against measles after
      6 months of age. Infant protection against measles could be optimized both by
      increasing herd immunity through an increased vaccine coverage and by lowering
      the age of routine vaccination from 12 to 9 months.

PMID- 18815233
TI  - Antibody responses of cervids (Cervus elaphus) following experimental
      Mycobacterium bovis infection and the implications for immunodiagnosis.
AB  - Captive and free-ranging wildlife animals are implicated in the maintenance and
      transmission of bovine tuberculosis and therefore pose a significant obstacle to
      eradication of the disease from domestic livestock. The current antemortem
      diagnostic method, the intradermal tuberculin skin test, is impractical for
      routine use with many wild animals. Antibody-based assays are particularly
      attractive because the animals are handled only once and immediate processing of
      the sample is not required. This report characterizes the antibody responses of
      red deer-elk hybrids (Cervus elaphus) against Mycobacterium bovis and
      subsequently evaluates the diagnostic performance of select antigens in a rapid
      test format. Sequential serum samples were collected from 10 animals
      experimentally infected with M. bovis and 5 noninfected animals over a 7-month
      period postinfection (p.i.). Samples were evaluated by enzyme-linked
      immunosorbent assays, immunoblot analyses, and multiantigen print immunoassays
      for seroreactivity to mycobacterial antigens. Although all infected animals
      produced antibodies to M. bovis protein antigens, there was significant animal-to
      animal variation in the kinetics and magnitudes of responses and the antigens
      recognized. The most frequently recognized antigens included MPB83, ESAT-6,
      CFP10, and MPB70. Responses to some antigens, such as MPB83, were consistently
      detected as early as 4 weeks after inoculation, whereas other antigens were
      detected only much later (>140 days p.i.). Antibody responses were boosted by
      injection of tuberculin for intradermal tuberculin skin testing. Comparison of
      single-antigen (fluorescence polarization assay) with multiantigen (CervidTB STAT
      PAK) rapid tests demonstrated that a highly sensitive and specific serodiagnostic
      test for tuberculosis in cervids will require multiple and carefully selected
      seroreactive antigens covering a broad spectrum of antibody specificities.

PMID- 18815234
TI  - Potentially exposed but uninfected individuals produce cytotoxic and
      polyfunctional human immunodeficiency virus type 1-specific CD8(+) T-cell
      responses which can be defined to the epitope level.
AB  - We measured CD8(+) T-cell responses in 12 potentially exposed but uninfected men
      who have sex with men by using cytokine flow cytometry. Four of the individuals
      screened exhibited polyfunctional immune responses to human immunodeficiency
      virus type 1 Gag or Vif. The minimum cytotoxic T lymphocyte epitope was mapped in
      one Gag responder.

PMID- 18815235
TI  - Role of the N-terminal amino acid of Bacillus anthracis lethal factor in lethal
      toxin cytotoxicity and its effect on the lethal toxin neutralization assay.
AB  - The cytotoxic activity of lethal factor (LF), a critical reagent used in the cell
      based lethal toxin neutralization assay to assess anthrax vaccines, was shown to
      depend on the identity of its N-terminal amino acid, which plays a role in the
      targeting of LF to the proteasome for degradation. These results demonstrate that
      care must be taken to ensure that LF preparations used in standardized cell-based
      assays are not altered at their N-terminal ends.

PMID- 18815236
TI  - Hindlimb growth after a transphyseal reconstruction of the anterior cruciate
      ligament: a study in skeletally immature sheep with wide-open physes.
AB  - BACKGROUND: There is a lot of controversy in the recent literature with regard to
      the optimal treatment of anterior cruciate ligament (ACL) injuries during growth.
      Iatrogenic growth disturbance due to physeal damage is a potential complication,
      forcing many orthopaedic surgeons to treat these injuries conservatively.
      HYPOTHESIS: It is possible to perform a fully transphyseal ACL reconstruction in
      an ovine model with wide-open physes without creating growth disturbances. STUDY
      DESIGN: Descriptive laboratory study. MATERIALS AND METHODS: Four-month-old
      skeletally immature sheep underwent a transphyseal ACL reconstruction of the
      right knee. The surgical technique followed the criteria known to be essential to
      avoid growth disturbances in humans; the tibial tuberosity was spared to prevent
      a genu recurvatum, thermal damage to the growth plates was avoided, the physes
      were perforated with a small-diameter drill in the center of the growth plate, a
      soft tissue graft was used, graft fixation was achieved far away from the growth
      plates, the perforated growth plates were filled by the soft tissue graft, and
      the graft was moderately pretensioned before fixation. The left knee served as a
      control. A computer-assisted evaluation of long radiographs (frontal and sagittal
      plane) of the exarticulated hindlimbs was performed to exactly evaluate the limb
      alignment, joint orientation, and leg length. The animals were sacrificed in
      groups of 6 after 3, 6, 12, and 24 weeks. RESULTS: No angular deformities or leg
      length discrepancies occurred after this transphyseal ACL reconstruction
      procedure throughout the remaining growth. CONCLUSION: This large-animal study
      supports the clinical observation that it is possible to perform an ACL
      reconstruction without creating growth disturbances as long as a number of key
      principles are followed. CLINICAL RELEVANCE: Previous animal studies argued
      against ACL reconstruction in skeletally immature patients. This large-animal
      study provides support for early operative treatment of ACL ruptures even in
      young patients with open physes.

PMID- 18815237
TI  - Native anterior cruciate ligament obliquity versus anterior cruciate ligament
      graft obliquity: an observational study using navigated measurements.
AB  - BACKGROUND: The goal of anterior cruciate ligament reconstruction is to attain a
      graft that closely resembles the native anterior cruciate ligament anatomy. By
      reconstructing the original anatomy, one hopes to eliminate issues related to
      graft elongation, impingement, and excessive tension while achieving ideal knee
      kinematics. HYPOTHESIS: Clinical grafts placed using the transtibial technique
      will differ in the sagittal and coronal planes when compared with obliquity of
      the anatomic anterior cruciate ligament. STUDY DESIGN: Controlled laboratory
      study/case series; Level of evidence, 4. METHODS: With the assistance of computer
      navigation, our study compared the anterior cruciate ligament orientation of 5
      cadaver knees with 12 clinical anterior cruciate ligament-reconstructed knees
      using the transtibial technique. RESULTS: Clinical graft obliquity differed from
      the anatomic anterior cruciate ligament in all flexion angles: 0 degrees, 30
      degrees, 60 degrees, and 90 degrees. In the sagittal plane, the clinical graft
      obliquity differed from the anatomic anterior cruciate ligament by 13.6 degrees,
      12.7 degrees, 16.7 degrees, and 17 degrees, respectively. In the coronal plane,
      the clinical graft obliquity differed from the anatomic anterior cruciate
      ligament by 4.9 degrees, 7.6 degrees, 8.9 degrees, and 12.7 degrees,
      respectively. Paired t tests demonstrated that the difference between the
      clinical and anatomic anterior cruciate ligament was significant (P <.05), except
      in the coronal plane at 0 degrees of flexion. In spite of this, all patients
      demonstrated a negative pivot shift and Lachman at the conclusion of their
      reconstructions and at 6-month follow-up. CONCLUSION: The sagittal and coronal
      plane obliquity of well-functioning grafts placed using the transtibial technique
      were more vertical than anatomic fibers. CLINICAL RELEVANCE: Graft obliquity, in
      both the coronal and sagittal plane, may be an important means to target
      appropriate anterior cruciate ligament graft position and can be monitored using
      surgical navigation systems.

PMID- 18815238
TI  - Effects of medial meniscus posterior horn avulsion and repair on tibiofemoral
      contact area and peak contact pressure with clinical implications.
AB  - BACKGROUND: Avulsion of the posterior horn attachment of the medial meniscus can
      compromise load-bearing ability, produce meniscus extrusion, and result in
      tibiofemoral joint-space narrowing, articular cartilage damage, and
      osteoarthritis. HYPOTHESIS: Avulsion of the posterior horn of the medial meniscus
      will increase peak contact pressure and decrease contact area in the medial
      compartment of the knee, and posterior horn repair will restore contact area and
      peak contact pressures to values of the control knee. STUDY DESIGN: Controlled
      laboratory study. METHODS: Eight fresh-frozen human cadaveric knees had
      tibiofemoral peak contact pressures and contact area measured in the control
      state. The posterior horn of the medial meniscus was avulsed from its insertion
      and knees were retested. The meniscal avulsion was repaired by suture through a
      transosseous tunnel and the knees were tested a third time. RESULTS: Avulsion of
      the posterior horn attachment of the medial meniscus resulted in a significant
      increase in medial joint peak contact pressure (from 3841 kPa to 5084 kPa) and a
      significant decrease in contact area (from 594 mm(2) to 474 mm(2)). Repair of the
      avulsion resulted in restoration of the loading profiles to values equal to the
      control knee, with values of 3551 kPa for peak pressure and 592 mm(2) for contact
      area. CONCLUSION: Posterior horn medial meniscal root avulsion leads to
      deleterious alteration of the loading profiles of the medial joint compartment
      and results in loss of hoop stress resistance, meniscus extrusion, abnormal
      loading of the joint, and early knee medial-compartment degenerative changes.
      CLINICAL RELEVANCE: The repair technique described restores the ability of the
      medial meniscus to absorb hoop stress and eliminate joint-space narrowing,
      possibly decreasing the risk of degenerative disease.

PMID- 18815239
TI  - Association of visceral and subcutaneous adiposity with kidney function.
AB  - BACKGROUND AND OBJECTIVES: Obesity is a risk factor for incident chronic kidney
      disease (CKD). Visceral (VAT) and subcutaneous adipose tissue (SAT) may confer
      differential metabolic risk profiles. The relations of VAT and SAT were analyzed
      with CKD as estimated by creatinine- and cystatin-based estimating equations.
      DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Participants from the Framingham
      Offspring Study who underwent abdominal computed tomography for VAT and SAT
      quantification were included (n = 1299; 53% women; mean age 60 yr). CKD was
      defined as estimated GFR <60 ml/min per 1.73 m(2), as estimated using creatinine
      (n = 89) in the Modification of Diet in Renal Disease (MDRD) formula or by
      cystatin C (n = 136). Regression models evaluated the cross-sectional relations
      between VAT and SAT with CKD and cystatin C, with age and gender adjustment and
      cardiovascular risk factor adjustment. RESULTS: Neither VAT nor SAT was
      associated with CKD as estimated by the MDRD equation. In contrast, both VAT and
      SAT were associated with CKD when defined using cystatin-based equations. The
      estimated decrease in estimated GFR by cystatin C per 1-SD increase of VAT was
      1.9 ml/min per 1.73 m(2) and for SAT was 2.6 ml/min per 1.73 m(2) in a
      multivariable-adjusted model. CONCLUSIONS: VAT and SAT were associated with CKD
      when defined using cystatin C estimating equations but not when using a
      creatinine-based estimating equation. Mechanisms linking adipose tissue to
      cystatin C warrant further research.

PMID- 18815240
TI  - Media calcification and intima calcification are distinct entities in chronic
      kidney disease.
AB  - Calcification of the vascular tree is common in physiologic and pathologic
      conditions, i.e., aging, diabetes, dyslipidemia, genetic diseases, and diseases
      with disturbances of calcium metabolism. In chronic kidney disease, vascular
      calcification is even more common, develops early, and contributes to the
      markedly increased cardiovascular risk in this particular population.
      Pathomorphologically, atherosclerosis (i.e., plaque-forming degenerative changes
      of the aorta and of large elastic arteries) and arteriosclerosis (i.e.,
      concentric media thickening of muscular arteries) can be distinguished.
      Increasing knowledge about calcification together with improved imaging
      techniques provided evidence that also vascular calcification has to be divided
      into two distinct entities according to the specific sites of calcification
      within the vascular wall: Patchy calcification of the intima in the vicinity of
      lipid or cholesterol deposits as present in plaque calcification and
      calcification of the media in the absence of such lipid or cholesterol deposits,
      known as Monckeberg-type atherosclerosis. The two types of calcification may vary
      according to the type of vessel (large elastic versus smaller muscular type
      artery) and proximal versus distal sites of the arterial tree. Furthermore,
      clinical studies showed that it is not purely academic to distinguish between
      intimal and medial calcification but rather relevant for the clinical
      presentation, treatment, and prognosis because each type leads to different
      clinical consequences. In vivo studies in animal models provided evidence in
      favor of common pathomechanisms between vascular calcification and
      atherosclerosis; however, there is other, strong experimental and clinical
      evidence that pleads for the continued distinction between intimal and medial
      calcification.

PMID- 18815241
TI  - Age, gender, and race effects on cystatin C levels in US adolescents.
AB  - BACKGROUND AND OBJECTIVES: The objective of this study was to describe the normal
      range of serum cystatin C and identify factors associated with variability in
      serum cystatin C contrasting with factors that are known to influence creatinine
      levels in the general US adolescent population. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: Serum cystatin C and creatinine were measured in 719 participants
      aged 12 to 19 yr in the Third National Health and Nutrition Examination Survey, a
      national cross-sectional survey conducted in 1988 through 1994. We calculated
      gender- and race/ethnicity-specific cystatin C and creatinine ranges and
      conducted multivariable linear regression analyses to assess factors that
      contribute to variability in cystatin C and creatinine levels. RESULTS: Overall,
      the mean serum cystatin C level was 0.84 mg/L and was higher in male than female
      individuals and higher in non-Hispanic white versus non-Hispanic black and
      Mexican American individuals. The mean serum creatinine was 0.71 mg/dl and was
      higher in male than in female individuals but lower in non-Hispanic white and
      Mexican American compared with non-Hispanic black individuals. Unlike creatinine,
      which increases with age from 12 to 19 yr, cystatin C levels decrease,
      particularly in female individuals. After adjustment for age, gender, and
      race/ethnicity, uric acid and blood urea nitrogen were significantly associated
      with cystatin C levels. CONCLUSIONS: Serum cystatin C is significantly related to
      gender, age, race/ethnicity, uric acid, and blood urea nitrogen in adolescents.

PMID- 18815242
TI  - Peritoneal phosphate clearance is influenced by peritoneal dialysis modality,
      independent of peritoneal transport characteristics.
AB  - BACKGROUND AND OBJECTIVES: Hyperphosphatemia is an independent risk factor for
      mortality in ESRD, but factors regulating phosphate clearance on peritoneal
      dialysis (PD) are incompletely understood. The objective of this study was to
      test the hypothesis that peritoneal phosphate clearance is better with continuous
      ambulatory PD (CAPD) as compared with continuous cyclic PD (CCPD) after adjusting
      for membrane transport status. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In
      this cross-sectional and retrospective study, measurements of peritoneal
      phosphate clearance of 129 prevalent PD patients were reviewed. Patients were
      divided according to membrane transport status (high, high average, low average
      low categories) and PD modality (CAPD or CCPD). RESULTS: Among high transporters,
      peritoneal phosphate clearances were comparable in both modalities. However,
      treatment with CAPD was associated with increased peritoneal phosphate clearance
      compared with CCPD among high-average transporters (42.4 +/- 11.4 versus 36.4 +/-
      8.3 L/wk/1.73 m(2), P = 0.01), and low-average-low transporters (35.6 +/- 5.9
      versus 28.9 +/- 11 L/wk/1.73 m(2), P = 0.034). On multivariate linear regression,
      PD modality, membrane transport category, and peritoneal creatinine clearance,
      but not Kt/V urea, were independently associated with peritoneal phosphate
      clearance. CONCLUSIONS: Peritoneal phosphate clearance is determined by PD
      modality and membrane transport category, suggesting that PD regimes with longer
      dwell times may help control hyperphosphatemia in lower transporters.

PMID- 18815243
TI  - Glomerular function, structure, and number in renal allografts from older
      deceased donors.
AB  - The 5-yr survival rate of renal allografts is significantly lower for grafts from
      older deceased donors than from younger deceased donors. For evaluation of the
      potential contribution of renal senescence in this shortened graft survival,
      glomerular function and structure were analyzed in allografts from deceased
      donors older than 55 yr ("aging") or younger than 40 yr ("youthful"). Aging
      donors had a significantly higher prevalence of sclerotic glomeruli (P < 0.002),
      and their nonsclerotic glomeruli tended to be larger, had a larger filtration
      surface area (P = 0.02), and had a higher single-nephron ultrafiltration
      coefficient (K(f); P = 0.07), suggesting a compensatory response to functional
      loss of glomeruli. After serum creatinine reached a stable nadir in the
      transplant recipients, GFR and its hemodynamic determinants were evaluated and
      the whole allograft K(f) was computed. Compared with the allografts from youthful
      donors, allografts from aging donors exhibited a 32% lower GFR, which was
      exclusively attributable to a 45% reduction in allograft K(f) (both P < 0.001).
      In addition, the number of functioning glomeruli per allograft was profoundly
      lower in grafts from aging donors than from youthful donors (3.6 +/- 2.1 x 10(5)
      versus 8.5 +/- 3.4 x 10(5); P < 0.01), and this could not be explained by the
      relatively modest 17% prevalence of global glomerulosclerosis in the aging group.
      The marked reduction in overall glomerular number in many aging donors may lead
      to a "remnant kidney" phenomenon, potentially explaining the shorter mean
      survival of these allografts.

PMID- 18815244
TI  - IL-18 contributes to renal damage after ischemia-reperfusion.
AB  - IL-18 is a proinflammatory cytokine produced by macrophages and other cell types
      present in the kidney during ischemia-reperfusion injury (IRI), but its role in
      this injury is unknown. Here, compared with wild-type mice, IL-18(-/-) mice
      subjected to kidney IRI demonstrated better kidney function, less tubular damage,
      reduced accumulation of neutrophils and macrophages, and decreased expression of
      proinflammatory molecules that are downstream of IL-18. For determination of the
      relative contributions of leukocytes and parenchymal cells to IL-18 production
      and subsequent kidney damage during IRI, bone marrow-chimeric mice were
      generated. Wild-type mice engrafted with IL-18(-/-) hemopoietic cells showed less
      kidney dysfunction and tubular damage than IL-18(-/-) mice engrafted with wild
      type bone marrow. In vitro, macrophages produced IL-18 mRNA and protein in
      response to ischemia. These data suggest bone marrow-derived cells are the key
      contributors to IL-18-mediated effects of renal IRI. Finally, similar to IL-18(-/
      ) mice, pretreatment of wild-type mice with IL-18-binding protein was
      renoprotective in this model of IRI. In conclusion, IL-18, derived primarily from
      cells of bone marrow origin, contributes to the renal damage observed during IRI.
      IL-18-binding protein may have potential as a renoprotective therapy.

PMID- 18815245
TI  - Zag expression during aging suppresses proliferation after kidney injury.
AB  - Recovery after acute kidney injury is impaired in the elderly, but mechanistic
      information regarding why this occurs is limited. In this study, aged mouse
      kidneys displayed a reduced epithelial proliferative reserve in vivo and in
      vitro. Microarray analysis identified increased expression of zinc-alpha (2)
      glycoprotein (Zag) in aged proximal tubular cells. The addition of recombinant
      Zag to primary renal epithelial cell cultures decreased proliferation, whereas
      knockdown of Zag increased proliferation. In vivo, systemic small interference
      RNA suppressed expression of Zag in the mouse proximal tubule; this increased the
      rate of epithelial cell proliferation after renal ischemia/reperfusion in aged
      mice but also increased parenchymal fibrosis. These results demonstrate that
      increased Zag expression in the aged kidney acts to suppress the proliferative
      response to injury and introduce Zag as a modifier of the aging phenotype.

PMID- 18815246
TI  - Schwann cells promote synaptogenesis at the neuromuscular junction via
      transforming growth factor-beta1.
AB  - Recent studies suggest that glial cells actively participate in the formation,
      function, maintenance, and repair of the chemical synapse. However, the molecular
      mechanisms of glia-synapse interactions are largely unknown. We have shown
      previously that Schwann cell-conditioned medium (SC-CM) promotes synaptogenesis
      in Xenopus nerve-muscle cocultures. The present study aimed to identify the
      synaptogenic molecules in SC-CM. Combining biochemical approaches and in vitro
      bioassays, we found that SC-CM contains transforming growth factor (TGF)-beta1,
      which is expressed in Schwann cells both in vivo and in vitro. Similar to SC-CM,
      TGF-beta1 doubled the size of acetylcholine receptor (AChR) clusters at nerve
      muscle contacts and significantly increased the percentage of nerve-muscle
      contacts that show AChR clusters to approximately 60%, compared with
      approximately 20% seen in control cultures. The synaptogenic effects of SC-CM
      were abolished if SC-CM was immunodepleted of TGF-beta1 or if the latency
      associated protein or a TGF-beta1 receptor kinase inhibitor was added to block
      the bioactivity of TGF-beta1. Similar to frog SC-CM, mammalian SC-CM also showed
      synaptogenic effects, which were prevented by immunodepletion of TGF-beta1. TGF
      beta1 upregulated agrin expression in spinal neurons, which could explain the
      increase in AChR clusters in cultures treated with SC-CM. These results suggest
      that Schwann cells express TGF-beta1, which is both sufficient and necessary for
      mediating the synapse-promoting effects of Schwann cells at the developing
      neuromuscular junction. Schwann cell-derived TGF-beta1 thus joins other astrocyte
      derived synaptogenic factors in further strengthening the emerging concept that
      glial cells contribute to synaptogenesis in both the PNS and the CNS.

PMID- 18815247
TI  - Consolidation patterns of human motor memory.
AB  - Can memories be unlearned, or is unlearning a form of acquiring a new memory that
      competes with the old, effectively masking it? We considered motor memories that
      were acquired when people learned to use a novel tool. We trained people to reach
      with tool A and quantified recall in error-clamp trials, i.e., trials in which
      the memory was reactivated but error-dependent learning was minimized. We
      measured both the magnitude of the memory and its resistance to change. With
      passage of time between acquisition and reactivation (up to 24 h), memory of A
      slowly declined, but with reactivation remained resistant to change. After
      learning of tool A, brief exposure to tool B brought performance back to
      baseline, i.e., apparent extinction. Yet, for up to a few minutes after A+B
      training, output in error-clamp trials increased from baseline to match those who
      had trained only in A. This spontaneous recovery and convergence demonstrated
      that B did not produce any unlearning of A. Rather, it masked A with a new memory
      that was very fragile. We tracked the memory of B as a function of time and found
      that within minutes it was transformed from a fragile to a more stable state.
      Therefore, a sudden performance error in a well-learned motor task does not
      produce unlearning, but rather installs a competing but fragile memory that with
      passage of time acquires stability. Learning not only engages processes that
      adapt at multiple timescales, but once practice ends, the fast states are
      partially transformed into slower states.

PMID- 18815248
TI  - Tripartite mechanism of extinction suggested by dopamine neuron activity and
      temporal difference model.
AB  - Extinction of behavior enables adaptation to a changing world and is crucial for
      recovery from disorders such as phobias and drug addiction. However, the brain
      mechanisms underlying behavioral extinction remain poorly understood. Midbrain
      dopamine (DA) neurons appear to play a central role in most acquisition processes
      of appetitive conditioning. Here, we show that the responses of putative DA
      neurons to conditioned reward predicting cues also dynamically encode two
      classical features of extinction: decrement in amplitude of previously learned
      excitatory responses and rebound of responding on subsequent retesting
      (spontaneous recovery). Crucially, this encoding involves development of
      inhibitory responses in the DA neurons, reflecting new, extinction-specific
      learning in the brain. We explored the implications of this finding by adding
      such inhibitory inputs to a standard temporal difference model of DA cell
      activity. We found that combining extinction-triggered plasticity of these inputs
      with a time-dependent spontaneous decay of weights, equivalent to a forgetting
      process as described in classical behavioral extinction literature, enabled the
      model to simulate several classical features of extinction. A key requirement to
      achieving spontaneous recovery was differential rates of spontaneous decay for
      weights representing original conditioning and for subsequent extinction
      learning. A testable prediction of the model is thus that differential decay
      properties exist within the wider circuits regulating DA cell activity. These
      findings are consistent with the hypothesis that extinction processes at both
      cellular and behavioral levels involve a dynamic interaction between new
      (inhibitory) learning, forgetting, and unlearning.

PMID- 18815249
TI  - Cortical plasticity induced by short-term unimodal and multimodal musical
      training.
AB  - Learning to play a musical instrument requires complex multimodal skills
      involving simultaneous perception of several sensory modalities: auditory,
      visual, somatosensory, as well as the motor system. Therefore, musical training
      provides a good and adequate neuroscientific model to study multimodal brain
      plasticity effects in humans. Here, we investigated the impact of short-term
      unimodal and multimodal musical training on brain plasticity. Two groups of
      nonmusicians were musically trained over the course of 2 weeks. One group
      [sensorimotor-auditory (SA)] learned to play a musical sequence on the piano,
      whereas the other group [auditory (A)] listened to and made judgments about the
      music that had been played by participants of the sensorimotor-auditory group.
      Training-induced cortical plasticity was assessed by recording the musically
      elicited mismatch negativity (MMNm) from magnetoencephalographic measurements
      before and after training. SA and A groups showed significantly different
      cortical responses after training. Specifically, the SA group showed significant
      enlargement of MMNm after training compared with the A group, reflecting greater
      enhancement of musical representations in auditory cortex after sensorimotor
      auditory training compared with after mere auditory training. Thus, we have
      experimentally demonstrated that not only are sensorimotor and auditory systems
      connected, but also that sensorimotor-auditory training causes plastic
      reorganizational changes in the auditory cortex over and above changes introduced
      by auditory training alone.

PMID- 18815250
TI  - Identification of transmembrane domain 5 as a critical molecular determinant of
      menthol sensitivity in mammalian TRPA1 channels.
AB  - TRPA1 is a member of the transient receptor potential (TRP) family of ion
      channels and is expressed in a subset of nociceptive neurons. An increasing body
      of evidence suggests that TRPA1 functions as a chemical nocisensor for a variety
      of reactive chemicals, such as pungent natural compounds and environmental
      irritants. Activation of TRPA1 by reactive compounds has been demonstrated to be
      mediated through covalent modification of cytoplasmic cysteines located in the N
      terminus of the channel, rather than classical lock-and-key binding. TRPA1
      activity is also modulated by numerous nonreactive chemicals, but the underlying
      mechanism is unknown. Menthol, a natural nonreactive cooling compound, is best
      known as an activator of TRPM8, a related TRP ion channel required for cool
      thermosensation in vivo. More recently, menthol has been shown to be an activator
      of mouse TRPA1 at low concentrations, and a blocker, at high concentrations.
      Here, we show that human TRPA1 is only activated by menthol, whereas TRPA1 from
      nonmammalian species are insensitive to menthol. Mouse-human TRPA1 chimeras
      reveal the pore region [including transmembrane domain 5 (TM5) and TM6] as the
      critical domain determining whether menthol can act as an inhibitor. Furthermore,
      chimeras between Drosophila melanogaster and mammalian TRPA1 highlight specific
      residues within TM5 critical for menthol responsiveness. Interestingly, this TM5
      region also determines the sensitivity of TRPA1 to other chemical modulators.
      These data suggest separable structural requirements for modulation of TRPA1 by
      covalent and nonreactive molecules. Whether this region is involved in binding or
      gating of TRPA1 channels is discussed.

PMID- 18815251
TI  - Driver or coincidence detector: modal switch of a corticothalamic giant synapse
      controlled by spontaneous activity and short-term depression.
AB  - Giant synapses between layer 5B (L5B) neurons of somatosensory (barrel) cortex
      and neurons of the posteromedial nucleus (POm) of thalamus reside in a key
      position of the cortico-thalamo-cortical (CTC) loop, yet their synaptic
      properties and contribution to CTC information processing remain poorly
      understood. Fluorescence-guided local stimulation of terminals were combined with
      postsynaptic whole-cell recordings in thalamus to study synaptic transmission at
      an identified giant synapse. We found large EPSCs mediated by Ca(2+)-permeable
      AMPA and NMDA receptors. A single presynaptic electrical stimulus evoked a train
      of postsynaptic action potentials, indicating that a single L5B input can
      effectively drive the thalamic neuron. Repetitive stimulation caused strong short
      term depression (STD) with fast recovery. To examine how these synaptic
      properties affect information transfer, spontaneous and evoked activity of L5B
      neurons was recorded in vivo and played back to giant terminals in vitro. We
      found that suprathreshold synaptic transmission was suppressed because of
      spontaneous activity causing strong STD of the L5B-POm giant synapse. Thalamic
      neurons only spiked after intervals of presynaptic silence or when costimulating
      two giant terminals. Therefore, STD caused by spontaneous activity of L5B neurons
      can switch the synapse from a "driver mode" to a "coincidence mode." Mechanisms
      decreasing spontaneous activity in L5B neurons and inputs synchronized by a
      sensory stimulus may thus gate the cortico-thalamo-cortical loop.

PMID- 18815252
TI  - Time-specific contribution of the supplementary motor area to intermanual
      transfer of procedural knowledge.
AB  - The supplementary motor area (SMA) makes a crucial contribution to intermanual
      transfer: the ability to use one hand to perform a skill practiced and learned
      with the other hand. However, the timing of this contribution relative to
      movement remains unknown. Here, 33 healthy volunteers performed a 12 item
      sequence in the serial reaction time task. During training, each participant
      responded to a sequence of visual cues presented at 1 Hz by pressing one of four
      keys with their right hand. The measure of intermanual transfer was response time
      (RT) during repetition of the trained sequence with the left hand, which was at
      rest during learning. Participants were divided into three groups, which did not
      differ in their learning rates or amounts. In two groups, 1 Hz repetitive
      transcranial magnetic stimulation induced transient virtual lesions of the SMA
      during training, either 100 ms before each cue (the premovement group) or during
      each key press (the movement group). The third group received sham stimulation
      (the sham group). After training with the right hand, RTs for performance with
      the left (transfer) hand were longer for the premovement group than for the
      movement or sham groups. Thus, the most crucial contribution of SMA to
      intermanual transfer occurs in the interval between movements, when the memory of
      a previous movement plays a role in encoding specific sequences. These results
      provide insight into frontal lobe contributions to procedural knowledge.

PMID- 18815253
TI  - Region-specific changes in the subcellular distribution of AMPA receptor GluR1
      subunit in the rat ventral tegmental area after acute or chronic morphine
      administration.
AB  - Opiate addiction is characterized by progressive increases in drug intake over
      time suggesting maladaptive changes in motivational and reward systems. These
      behaviors are mediated by dopaminergic neurons originating from the ventral
      tegmental area (VTA), and long-term changes of these dopaminergic neurons are
      attributed to increased postsynaptic glutamatergic activation. Indeed, chronic
      morphine administration is known to increase AMPA receptor glutamate receptor 1
      (GluR1) subunit in the VTA. However, there is no ultrastructural evidence that
      morphine affects the expression or surface availability of GluR1 subunits in VTA
      neurons of defined distribution or transmitter phenotype. Therefore, we examined
      electron microscopic immunolabeling of GluR1 and tyrosine hydroxylase (TH) in two
      VTA regions of rats perfused 1 h after a single injection of morphine, or chronic
      morphine in intermittent-escalating doses for 14 d, and appropriate saline
      controls. Acute morphine administration produced a significant increase in GluR1
      immunogold particles at the plasma membrane and postsynaptic densities in both TH
      and non-TH-containing dendrites in the parabrachial VTA, a region that contains
      mainly prefrontal-cortical-projecting dopaminergic neurons involved in motivation
      and drug-seeking behavior. Chronic morphine administration maintained the
      increased synaptic GluR1 labeling in the parabrachial VTA, but also increased the
      number of GluR1-labeled synapses and TH immunoreactivity in dendrites of the
      paranigral VTA where substantially more dopaminergic neurons project to limbic
      structures implicated in locomotor activation and reward. These results
      demonstrate a region- and dose-dependent redistribution of GluR1-containing AMPA
      receptors, which is consistent with acute morphine activation of cortical
      projecting VTA neurons and chronic morphine activation of limbic-projecting VTA
      neurons.

PMID- 18815254
TI  - Mitochondria modulate Ca2+-dependent glutamate release from rat cortical
      astrocytes.
AB  - Vesicular glutamate release from astrocytes depends on mobilization of free
      Ca(2+) from the endoplasmic reticulum (ER), and extracellular space to elevate
      cytosolic Ca(2+) (Ca(2+)(cyt)). Although mitochondria in neurons, and other
      secretory cells, have been shown to sequester free Ca(2+) and have been
      implicated in the modulation of Ca(2+)-dependent transmitter release, the role of
      mitochondria in Ca(2+)-dependent glutamate release from astrocytes is not known.
      A pharmacological approach was taken to manipulate Ca(2+) accumulation in
      mitochondria and thereby affect Ca(2+)(cyt) of solitary astrocytes in response to
      mechanical stimuli. Ca(2+)(cyt) responses and levels of glutamate release were
      measured optically in parallel experiments using a fluorescent Ca(2+) indicator
      and an enzyme-linked assay, respectively. It was observed that inhibiting
      mitochondrial Ca(2+) accumulation is correlated to increased Ca(2+)(cyt) and
      glutamate release, whereas enhancing mitochondrial Ca(2+) accumulation is
      correlated to decreased Ca(2+)(cyt) and glutamate release. These observations
      suggest that, in addition to the activity of ER and plasma membrane ion channels,
      mitochondria modulate Ca(2+)(cyt) dynamics in astrocytes and play a role in
      Ca(2+)-dependent glutamate release from astrocytes.

PMID- 18815255
TI  - Numbers, densities, and colocalization of AMPA- and NMDA-type glutamate receptors
      at individual synapses in the superficial spinal dorsal horn of rats.
AB  - Ionotropic glutamate receptors play important roles in spinal processing of
      nociceptive sensory signals and induction of central sensitization in chronic
      pain. Here we applied highly sensitive freeze-fracture replica labeling to
      laminae I-II of the spinal dorsal horn of rats and investigated the numbers,
      densities, and colocalization of AMPA- and NMDA-type glutamate receptors at
      individual postsynaptic membrane specializations with a high resolution. All
      glutamatergic postsynaptic membranes in laminae I-II expressed AMPA receptors,
      and most of them (96%) were also immunoreactive for the NR1 subunit of NMDA
      receptors. The numbers of gold particles for AMPA and NMDA receptors at
      individual postsynaptic membranes showed a linear correlation with the size of
      postsynaptic membrane specializations and varied in the range of 8-214 and 5-232
      with median values of 37 and 28, whereas their densities varied in the range of
      325-3365/microm(2) and 102-2263/microm(2) with median values of 1115/microm(2)
      and 777/microm(2), respectively. Virtually all (99%) glutamatergic postsynaptic
      membranes expressed GluR2, and most of them (87%) were also immunoreactive for
      GluR1. The numbers of gold particles for pan-AMPA, NR1, and GluR2 subunits showed
      a linear correlation with the size of postsynaptic surface areas. Concerning
      GluR1, there may be two populations of synapses with high and low GluR1
      densities. In synapses larger than 0.1 microm(2), GluR1 subunits were recovered
      in very low numbers. Differential expression of GluR1 and GluR2 subunits suggests
      regulation of AMPA receptor subunit composition by presynaptic mechanism.

PMID- 18815256
TI  - Activating parabrachial cannabinoid CB1 receptors selectively stimulates feeding
      of palatable foods in rats.
AB  - The endocannabinoid system is emerging as an integral component in central and
      peripheral regulation of feeding and energy balance. Our investigation analyzed
      behavioral roles for cannabinoid mechanisms of the pontine parabrachial nucleus
      (PBN) in modulating intake of presumably palatable foods containing fat and/or
      sugar. The PBN serves to gate neurotransmission associated with, but not limited
      to, the gustatory properties of food. Immunofluorescence and in vitro
      [(35)S]GTPgammaS autoradiography of rat tissue sections containing the PBN
      revealed the presence of cannabinoid receptors and their functional capability to
      couple to their G-proteins after incubation with the endocannabinoid 2
      arachidonoyl glycerol (2-AG). The selective cannabinoid 1 receptor (CB(1)R)
      antagonist AM251 [N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4
      methyl-1H-pyrazole-3-carboxamide] prevented the response, demonstrating CB(1)R
      mediation of 2-AG-induced coupling. Microinfusions of 2-AG into the PBN in
      behaving rats robustly stimulated feeding of pellets high in content of fat and
      sucrose (HFS), pure sucrose, and pure fat (Crisco), during the first 30 min after
      infusion. In contrast, 2-AG failed to increase consumption of standard chow, even
      when the feeding regimen was manipulated to match baseline intakes of HFS.
      Orexigenic responses to 2-AG were attenuated by AM251, again indicating CB(1)R
      mediation of 2-AG actions. Furthermore, responses were regionally specific,
      because 2-AG failed to alter intake when infused into sites approximately 500 mum
      caudal to infusions that successfully stimulated feeding. Our data suggest that
      hedonically positive sensory properties of food enable endocannabinoids at PBN
      CB(1)Rs to initiate increases in eating, and, more generally, these pathways may
      serve a larger role in brain functions controlling behavioral responses for
      natural reward.

PMID- 18815257
TI  - Precise and fuzzy coding by olfactory sensory neurons.
AB  - The exact nature of the olfactory signals that arrive in the brain from the
      periphery, and their reproducibility, remain essentially unknown. In most
      organisms, the sheer number of olfactory sensory neurons (OSNs) makes it
      impossible to measure the individual responses of the entire population. We
      measured the individual in situ electrophysiological activity of OSNs in
      Drosophila larvae, in response to stimulation with 10 aliphatic odors (alcohols
      and esters). We studied control larvae (a total of 296 OSNs) and larvae with a
      single functional OSN, created using the Gal4-upstream activator sequence system.
      Most OSNs showed consistent, precise responses (either excitation or inhibition)
      in response to a given odor. Some OSNs also showed qualitatively variable
      responses ("fuzzy coding"). This robust variability was an intrinsic property of
      these neurons: it was not attributable to odor type, concentration, stimulus
      duration, genotype, or interindividual differences, and was seen in control
      larvae and in larvae with one and two functional OSNs. We conclude that in
      Drosophila larvae the peripheral code combines precise coding with fuzzy,
      stochastic responses in which neurons show qualitative variability in their
      responses to a given odor. We hypothesize that fuzzy coding occurs in other
      organisms, is translated into differing degrees of activation of the glomeruli,
      and forms a key component of response variability in the first stages of
      olfactory processing.

PMID- 18815258
TI  - Dysregulation of gene expression in primary neuron models of Huntington's disease
      shows that polyglutamine-related effects on the striatal transcriptome may not be
      dependent on brain circuitry.
AB  - Gene expression changes are a hallmark of the neuropathology of Huntington's
      disease (HD), but the exact molecular mechanisms of this effect remain uncertain.
      Here, we report that in vitro models of disease comprised of primary striatal
      neurons expressing N-terminal fragments of mutant huntingtin (via lentiviral gene
      delivery) faithfully reproduce the gene expression changes seen in human HD.
      Neither viral infection nor unrelated (enhanced green fluorescent protein)
      transgene expression had a major effect on resultant RNA profiles. Expression of
      a wild-type fragment of huntingtin [htt171-18Q] also caused only a small number
      of RNA changes. The disease-related signal in htt171-82Q versus htt171-18Q
      comparisons was far greater, resulting in the differential detection of 20% of
      all mRNA probe sets. Transcriptomic effects of mutated htt171 are time- and
      polyglutamine-length dependent and occur in parallel with other manifestations of
      polyglutamine toxicity over 4-8 weeks. Specific RNA changes in htt171-82Q
      expressing striatal cells accurately recapitulated those observed in human HD
      caudate and included decreases in PENK (proenkephalin), RGS4 (regulator of G
      protein signaling 4), dopamine D(1) receptor (DRD1), DRD2, CNR1 (cannabinoid
      CB(1) receptor), and DARPP-32 (dopamine- and cAMP-regulated phosphoprotein-32;
      also known as PPP1R1B) mRNAs. HD-related transcriptomic changes were also
      observed in primary neurons expressing a longer fragment of mutant huntingtin
      (htt853-82Q). The gene expression changes observed in cultured striatal neurons
      are not secondary to abnormalities of neuronal firing or glutamatergic,
      dopaminergic, or brain-derived neurotrophic factor signaling, thereby
      demonstrating that HD-induced dysregulation of the striatal transcriptome might
      be attributed to intrinsic effects of mutant huntingtin.

PMID- 18815260
TI  - Absence of 2-hydroxylated sphingolipids is compatible with normal neural
      development but causes late-onset axon and myelin sheath degeneration.
AB  - Sphingolipids containing 2-hydroxylated fatty acids are among the most abundant
      lipid components of the myelin sheath and therefore are thought to play an
      important role in formation and function of myelin. To prove this hypothesis, we
      generated mice lacking a functional fatty acid 2-hydroxylase (FA2H) gene. FA2H
      deficient (FA2H(-/-)) mice lacked 2-hydroxylated sphingolipids in the brain and
      in peripheral nerves. In contrast, nonhydroxylated galactosylceramide was
      increased in FA2H(-/-) mice. However, oligodendrocyte differentiation examined by
      in situ hybridization with cRNA probes for proteolipid protein and PDGFalpha
      receptor and the time course of myelin formation were not altered in FA2H(-/-)
      mice compared with wild-type littermates. Nerve conduction velocity measurements
      of sciatic nerves revealed no significant differences between FA2H(-/-) and wild
      type mice. Moreover, myelin of FA2H(-/-) mice up to 5 months of age appeared
      normal at the ultrastructural level, in the CNS and peripheral nervous system.
      Myelin thickness and g-ratios were normal in FA2H(-/-) mice. Aged (18-month-old)
      FA2H(-/-) mice, however, exhibited scattered axonal and myelin sheath
      degeneration in the spinal cord and an even more pronounced loss of stainability
      of myelin sheaths in sciatic nerves. These results show that structurally and
      functionally normal myelin can be formed in the absence of 2-hydroxylated
      sphingolipids but that its long-term maintenance is strikingly impaired. Because
      axon degeneration appear to start rather early with respect to myelin
      degenerations, these lipids might be required for glial support of axon function.

PMID- 18815259
TI  - TIMELESS is an important mediator of CK2 effects on circadian clock function in
      vivo.
AB  - Circadian oscillations in clock components are central to generation of self
      sustained 24-h periodicity. In the Drosophila molecular clock, accumulation,
      phosphorylation, and degradation of PERIOD (PER) and TIMELESS (TIM) proteins
      govern period length. Yet little is known about the kinases that phosphorylate
      TIM in vivo. It has been shown previously that the protein kinase CK2
      phosphorylates TIM in vitro. Here, we identify a role for CK2 in TIM regulation
      in vivo. Induction of a dominant-negative CK2alpha, CK2alpha(Tik) (Tik),
      increases TIM protein and tim transcript levels, reduces oscillation amplitude,
      and results in persistent cytoplasmic TIM localization. Exposure to light and
      subsequent TIM degradation results in an increase in the fraction of the
      transcriptional repressor PER that is nuclear and suppression of per and tim RNA
      levels. TIM protein, but not tim transcript, levels are elevated in Tik mutants
      in a per(01) background. In contrast, Tik effects on PER are undetectable in a
      tim(01) background, suggesting that TIM is required for CK2 effects on PER. To
      identify potential CK2 target sites, we assayed TIM phosphorylation rhythms in a
      deletion mutant that removes a conserved serine-rich domain and found that TIM
      protein does not show robust rhythmic changes in mobility by Western blotting, a
      hallmark of rhythmic phosphorylation. The period lengthening effects in Tik
      heterozygotes are reduced in a tim(UL) mutant that disrupts a putative CK2
      phosphorylation site. Together, these data indicate that TIM is an important
      mediator of CK2 effects on circadian rhythms.

PMID- 18815261
TI  - The glycine transporter GlyT2 controls the dynamics of synaptic vesicle refilling
      in inhibitory spinal cord neurons.
AB  - At inhibitory synapses, glycine and GABA are accumulated into synaptic vesicles
      by the same vesicular transporter VGAT/VIAAT (vesicular GABA
      transporter/vesicular inhibitory amino acid transporter), enabling a continuum of
      glycine, GABA, and mixed phenotypes. Many fundamental aspects of the presynaptic
      contribution to the inhibitory phenotypes remain unclear. The neuronal
      transporter GlyT2 is one of the critical presynaptic factors, because glycinergic
      transmission is impaired in knock-out GlyT2(-/-) mice and mutations in the human
      GlyT2 gene slc6a5 are sufficient to cause hyperekplexia. Here, we establish that
      GlyT2-mediated uptake is directly coupled to the accumulation of glycine into
      recycling synaptic vesicles using cultured spinal cord neurons derived from GlyT2
      enhanced green fluorescent protein transgenic mice. Membrane expression of GlyT2
      was confirmed by recording glycine-evoked transporter current. We show that GlyT2
      inhibition induces a switch from a predominantly glycine to a predominantly GABA
      phenotype. This effect was mediated by a reduction of glycinergic quantal size
      after cytosolic depletion of glycine and was entirely reversed by glycine
      resupply, illustrating that the filling of empty synaptic vesicles is tightly
      coupled to GlyT2-mediated uptake. Interestingly, high-frequency trains of stimuli
      elicit two phases of vesicle release with distinct kinetic requirements for
      glycine refilling. Thus, our results demonstrate the central role played by GlyT2
      in determining inhibitory phenotype and therefore in the physiology and pathology
      of inhibitory circuits.

PMID- 18815262
TI  - Connexin45-containing neuronal gap junctions in rodent retina also contain
      connexin36 in both apposing hemiplaques, forming bihomotypic gap junctions, with
      scaffolding contributed by zonula occludens-1.
AB  - Mammalian retinas contain abundant neuronal gap junctions, particularly in the
      inner plexiform layer (IPL), where the two principal neuronal connexin proteins
      are Cx36 and Cx45. Currently undetermined are coupling relationships between
      these connexins and whether both are expressed together or separately in a
      neuronal subtype-specific manner. Although Cx45-expressing neurons strongly
      couple with Cx36-expressing neurons, possibly via heterotypic gap junctions, Cx45
      and Cx36 failed to form functional heterotypic channels in vitro. We now show
      that Cx36 and Cx45 coexpressed in HeLa cells were colocalized in
      immunofluorescent puncta between contacting cells, demonstrating
      targeting/scaffolding competence for both connexins in vitro. However, Cx36 and
      Cx45 expressed separately did not form immunofluorescent puncta containing both
      connexins, supporting lack of heterotypic coupling competence. In IPL, 87% of
      Cx45-immunofluorescent puncta were colocalized with Cx36, supporting either
      widespread heterotypic coupling or bihomotypic coupling. Ultrastructurally, Cx45
      was detected in 9% of IPL gap junction hemiplaques, 90-100% of which also
      contained Cx36, demonstrating connexin coexpression and cotargeting in virtually
      all IPL neurons that express Cx45. Moreover, double replicas revealed both
      connexins in separate domains mirrored on both sides of matched hemiplaques. With
      previous evidence that Cx36 interacts with PDZ1 domain of zonula occludens-1 (ZO
      1), we show that Cx45 interacts with PDZ2 domain of ZO-1, and that Cx36, Cx45,
      and ZO-1 coimmunoprecipitate, suggesting that ZO-1 provides for coscaffolding of
      Cx45 with Cx36. These data document that in Cx45-expressing neurons of IPL, Cx45
      is almost always accompanied by Cx36, forming "bihomotypic" gap junctions, with
      Cx45 structurally coupling to Cx45 and Cx36 coupling to Cx36.

PMID- 18815263
TI  - Function and structure of the right inferior frontal cortex predict individual
      differences in response inhibition: a model-based approach.
AB  - The ability to suppress one's impulses and actions constitutes a fundamental
      mechanism of cognitive control, thought to be subserved by the right inferior
      frontal cortex (rIFC). The neural bases of more selective inhibitory control when
      selecting between two actions have thus far remained articulated with less
      precision. Selective inhibition can be explored in detail by extracting
      parameters from response time (RT) distributions as derived from performance in
      the Simon task. Individual differences in RT distribution parameters not only can
      be used to probe the efficiency and temporal dynamics of selective response
      inhibition, but also allow a more detailed analysis of functional neuroimaging
      data. Such model-based analyses, which capitalize on individual differences, have
      demonstrated that selective response inhibition is subserved by the rIFC. The aim
      of the present study was to specify the relationship between model parameters of
      response inhibition and their functional and structural underpinnings in the
      brain. Functional magnetic resonance imaging (fMRI) data were obtained from
      healthy participants while performing a Simon task in which irrelevant
      information can activate incorrect responses that should be selectively inhibited
      in favor of selecting the correct response. In addition, structural data on the
      density of coherency of white matter tracts were obtained using diffusion tensor
      imaging (DTI). The analyses aimed at quantifying the extent to which RT
      distribution measures of response inhibition are associated with individual
      differences in both rIFC function and structure. The results revealed a strong
      correlation between the model parameters and both fMRI and DTI characteristics of
      the rIFC. In general, our results reveal that individual differences in
      inhibition are accompanied by differences in both brain function and structure.

PMID- 18815264
TI  - Critical role of the prefrontal cortex in the regulation of hippocampus-accumbens
      information flow.
AB  - The nucleus accumbens (NAc) is an integral part of limbic circuits proposed to
      play a central role in the pathophysiology of schizophrenia, and is positioned to
      integrate information from limbic and cortical regions, including the medial
      prefrontal cortex (mPFC) and the hippocampus. The ventral subiculum (vSub) of the
      hippocampus, in particular, is proposed to gate information flow within the NAc,
      a factor that is disrupted in models of schizophrenia. Using in vivo
      extracellular recordings in anesthetized rats, we examined the response of NAc
      neurons to vSub stimulation and how this is modulated by the mPFC. We found that
      inactivation of mPFC by tetrodotoxin attenuates the ability of the vSub to drive
      spike firing in the NAc. Thus, a contribution of the mPFC is required for the
      activation of NAc by the vSub. However, when long-term potentiation is induced in
      the vSub-NAc pathway, the vSub is now capable of driving the NAc without the
      participation of the mPFC. Moreover, this interaction is dependent on activation
      of dopaminergic D(2) receptors in the NAc. This work demonstrates the critical
      role of the mPFC in the ability of vSub to drive NAc neurons in normal
      anesthetized animals. One model of schizophrenia posits that vSub hyperactivity
      may underlie both the hyperdopaminergic state and disruption of information flow
      in this circuit in schizophrenia. Therefore, inactivation of the mPFC, as would
      occur with mPFC leukotomy in schizophrenia, may prevent the abnormal vSub drive
      of the NAc.

PMID- 18815265
TI  - Facilitatory mechanisms underlying selectivity for the direction and rate of
      frequency modulated sweeps in the auditory cortex.
AB  - Neurons selective for frequency modulated (FM) sweeps are common in auditory
      systems across different vertebrate groups and may underlie representation of
      species-specific vocalizations. Studies on mechanisms of FM sweep selectivity
      have primarily focused on sideband inhibition. Here, we present the first
      evidence for facilitatory mechanisms of FM sweep selectivity. Facilitatory
      interactions were found in 46 of 264 (17%) neurons tuned in the echolocation
      range (25-60 kHz) in the auditory cortex of the pallid bat. These neurons respond
      poorly to individual tones but are facilitated by combinations of tones with
      specific spectral and temporal intervals. Facilitation neurons show remarkable
      sensitivity to sub-millisecond differences in time delays between the two tones.
      Interestingly, the range of delays eliciting facilitation is not fixed but varies
      systematically with frequency difference between the two tones. Properties of
      facilitation strongly predict selectivity for the direction and rate of FM
      sweeps. Together with previous studies, there appear to be at least three
      mechanisms underlying FM rate and direction selectivity: sideband inhibition,
      duration tuning, and facilitation. Interestingly, similar mechanisms underlie
      direction and velocity tuning in the visual system, suggesting the evolution of
      similar computations across sensory systems to process dynamic sensory stimuli.

PMID- 18815266
TI  - Experience-dependent plasticity from eye opening enables lasting, visual cortex
      dependent enhancement of motion vision.
AB  - Developmentally regulated plasticity of vision has generally been associated with
      "sensitive" or "critical" periods in juvenile life, wherein visual deprivation
      leads to loss of visual function. Here we report an enabling form of visual
      plasticity that commences in infant rats from eye opening, in which daily
      threshold testing of optokinetic tracking, amid otherwise normal visual
      experience, stimulates enduring, visual cortex-dependent enhancement (>60%) of
      the spatial frequency threshold for tracking. The perceptual ability to use
      spatial frequency in discriminating between moving visual stimuli is also
      improved by the testing experience. The capacity for inducing enhancement is
      transitory and effectively limited to infancy; however, enhanced responses are
      not consolidated and maintained unless in-kind testing experience continues
      uninterrupted into juvenile life. The data show that selective visual experience
      from infancy can alone enable visual function. They also indicate that plasticity
      associated with visual deprivation may not be the only cause of developmental
      visual dysfunction, because we found that experientially inducing enhancement in
      late infancy, without subsequent reinforcement of the experience in early
      juvenile life, can lead to enduring loss of function.

PMID- 18815267
TI  - Developmental regulation of neuromodulator function in the stomatogastric
      ganglion of the lobster, Homarus americanus.
AB  - Neuromodulatory substances have profound effects on the two motor patterns
      generated by the adult crustacean stomatogastric ganglion (STG), the gastric mill
      rhythm and the pyloric rhythm. Developmentally regulated changes in the
      modulatory functions of neuromodulators could therefore play an important role in
      the maturation of the output from the developing STG. We compared the effects of
      neuromodulators on isolated embryonic and adult STG of the lobster, Homarus
      americanus. Bath application of Val(1)-SIFamide, a peptide whose expression is
      different in embryos and adults, activated different neuron classes in embryos
      and adults. Cancer borealis tachykinin-related peptide 1a, a peptide that does
      not appear in the terminals of modulatory neurons in the STG until after
      embryonic development, also produced different motor patterns in embryos and
      adults. In contrast, red pigment concentrating hormone, a peptide with a similar
      distribution in the STNS across development, produced similar motor patterns in
      embryonic and adult STG. Proctolin, serotonin, and allatostatin were also
      physiologically active on the isolated embryonic STG. Together, these results
      demonstrate that receptors to many neuromodulators are present and functional on
      STG neurons before the motor patterns of the stomatogastric nervous system are
      mature. Moreover, neuromodulator responses change during development, perhaps
      contributing to the maturation of the output from the stomatogastric nervous
      system.

PMID- 18815268
TI  - Involvement of the limbic basal ganglia in ethanol withdrawal convulsivity in
      mice is influenced by a chromosome 4 locus.
AB  - Physiological dependence and associated withdrawal episodes are thought to
      constitute a motivational force that sustains ethanol (alcohol) use/abuse and may
      contribute to relapse in alcoholics. Although no animal model duplicates
      alcoholism, models for specific factors, like the withdrawal syndrome, are useful
      for identifying potential genetic and neural determinants of liability in humans.
      We generated congenic mice that confirm a quantitative trait locus (QTL) on
      chromosome 4 with a large effect on predisposition to alcohol withdrawal. Using c
      Fos expression as a high-resolution marker of neuronal activation, congenic mice
      demonstrated significantly less neuronal activity associated with ethanol
      withdrawal than background strain mice in the substantia nigra pars reticulata
      (SNr), subthalamic nucleus (STN), rostromedial lateral globus pallidus, and
      ventral pallidum. Notably, neuronal activation in subregions of the basal ganglia
      associated with limbic function was more intense than in subregions associated
      with sensorimotor function. Bilateral lesions of caudolateral SNr attenuated
      withdrawal severity after acute and repeated ethanol exposures, whereas
      rostrolateral SNr and STN lesions did not reduce ethanol withdrawal severity.
      Caudolateral SNr lesions did not affect pentylenetetrazol-enhanced convulsions.
      Our results suggest that this QTL impacts ethanol withdrawal via basal ganglia
      circuitry associated with limbic function and that the caudolateral SNr plays a
      critical role. These are the first analyses to elucidate circuitry by which a
      confirmed addiction-relevant QTL influences behavior. This mouse QTL is syntenic
      with human chromosome 9p. Given the growing body of evidence that a gene(s) on
      chromosome 9p influences alcoholism, our results can facilitate human research on
      alcohol dependence and withdrawal.

PMID- 18815269
TI  - Increased vesicular monoamine transporter binding during early abstinence in
      human methamphetamine users: Is VMAT2 a stable dopamine neuron biomarker?
AB  - Animal data indicate that methamphetamine can damage striatal dopamine terminals.
      Efforts to document dopamine neuron damage in living brain of methamphetamine
      users have focused on the binding of [(11)C]dihydrotetrabenazine (DTBZ), a
      vesicular monoamine transporter (VMAT2) positron emission tomography (PET)
      radioligand, as a stable dopamine neuron biomarker. Previous PET data report a
      slight decrease in striatal [(11)C]DTBZ binding in human methamphetamine users
      after prolonged (mean, 3 years) abstinence, suggesting that the reduction would
      likely be substantial in early abstinence. We measured striatal VMAT2 binding in
      16 recently withdrawn (mean, 19 d; range, 1-90 d) methamphetamine users and in 14
      healthy matched-control subjects during a PET scan with (+)[(11)C]DTBZ.
      Unexpectedly, striatal (+)[(11)C]DTBZ binding was increased in methamphetamine
      users relative to controls (+22%, caudate; +12%, putamen; +11%, ventral
      striatum). Increased (+)[(11)C]DTBZ binding in caudate was most marked in
      methamphetamine users abstinent for 1-3 d (+41%), relative to the 7-21 d (+15%)
      and >21 d (+9%) groups. Above-normal VMAT2 binding in some drug users suggests
      that any toxic effect of methamphetamine on dopamine neurons might be masked by
      an increased (+)[(11)C]DTBZ binding and that VMAT2 radioligand binding might not
      be, as is generally assumed, a "stable" index of dopamine neuron integrity in
      vivo. One potential explanation for increased (+)[(11)C]DTBZ binding is that
      VMAT2 binding is sensitive to changes in vesicular dopamine storage levels,
      presumably low in drug users. If correct, (+)[(11)C]DTBZ might be a useful
      imaging probe to correlate changes in brain dopamine stores and behavior in users
      of methamphetamine.

PMID- 18815271
TI  - Induction of proneurotrophins and activation of p75NTR-mediated apoptosis via
      neurotrophin receptor-interacting factor in hippocampal neurons after seizures.
AB  - Seizure-induced damage elicits a loss of hippocampal neurons mediated to a great
      extent by the p75 neurotrophin receptor (NTR). Proneurotrophins, which are potent
      apoptosis-inducing ligands for p75(NTR), were increased in the hippocampus,
      particularly in astrocytes, by pilocarpine-induced seizures; and infusion of anti
      pro-NGF dramatically attenuated neuronal loss after seizures. The p75(NTR) is
      expressed in many different cell types in the nervous system, and can mediate a
      variety of different cellular functions by recruiting specific intracellular
      binding proteins to activate distinct signaling pathways. In this study, we
      demonstrate that neurotrophin receptor-interacting factor (NRIF) mediates
      apoptotic signaling via p75(NTR) in hippocampal neurons in vitro and in vivo.
      After seizure-induced injury, NRIF(-/-) mice showed an increase in p75(NTR)
      expression in the hippocampus; however, these neurons failed to undergo apoptosis
      in contrast to wild-type mice. Treatment of cultured hippocampal neurons with
      proneurotrophins induced association of NRIF with p75(NTR) and subsequent
      translocation of NRIF to the nucleus, which was dependent on cleavage of the
      receptor. Neurons lacking NRIF were resistant to p75(NTR)-mediated apoptosis in
      vitro and in vivo. In addition, we demonstrate some mechanistic differences in
      p75(NTR) signaling in hippocampal neurons compared with other cell types.
      Overall, these studies demonstrate the requirement for NRIF to signal p75(NTR)
      mediated apoptosis of hippocampal neurons and that blocking pro-NGF can inhibit
      neuronal loss after seizures.

PMID- 18815270
TI  - The neurotrophin-inducible gene Vgf regulates hippocampal function and behavior
      through a brain-derived neurotrophic factor-dependent mechanism.
AB  - VGF is a neurotrophin-inducible, activity-regulated gene product that is
      expressed in CNS and PNS neurons, in which it is processed into peptides and
      secreted. VGF synthesis is stimulated by BDNF, a critical regulator of
      hippocampal development and function, and two VGF C-terminal peptides increase
      synaptic activity in cultured hippocampal neurons. To assess VGF function in the
      hippocampus, we tested heterozygous and homozygous VGF knock-out mice in two
      different learning tasks, assessed long-term potentiation (LTP) and depression
      (LTD) in hippocampal slices from VGF mutant mice, and investigated how VGF C
      terminal peptides modulate synaptic plasticity. Treatment of rat hippocampal
      slices with the VGF-derived peptide TLQP62 resulted in transient potentiation
      through a mechanism that was selectively blocked by the BDNF scavenger TrkB-Fc,
      the Trk tyrosine kinase inhibitor K252a (100 nm), and tPA STOP, an inhibitor of
      tissue plasminogen activator (tPA), an enzyme involved in pro-BDNF cleavage to
      BDNF, but was not blocked by the NMDA receptor antagonist APV, anti-p75(NTR)
      function-blocking antiserum, or previous tetanic stimulation. Although LTP was
      normal in slices from VGF knock-out mice, LTD could not be induced, and VGF
      mutant mice were impaired in hippocampal-dependent spatial learning and
      contextual fear conditioning tasks. Our studies indicate that the VGF C-terminal
      peptide TLQP62 modulates hippocampal synaptic transmission through a BDNF
      dependent mechanism and that VGF deficiency in mice impacts synaptic plasticity
      and memory in addition to depressive behavior.

PMID- 18815272
TI  - The genomic response of the retinal pigment epithelium to light damage and
      retinal detachment.
AB  - The retinal pigment epithelium (RPE) plays an essential role in maintaining the
      health of the retina. The RPE is also the site of pathologic processes in a wide
      variety of retinal disorders including monogenic retinal dystrophies, age-related
      macular degeneration, and retinal detachment. Despite intense interest in the
      RPE, little is known about its molecular response to ocular damage or disease. We
      have conducted a comprehensive analysis of changes in transcript abundance (the
      "genomic response") in the murine RPE after light damage. Several dozen
      transcripts, many related to cell-cell signaling, show significant increases in
      abundance in response to bright light; transcripts encoding visual cycle proteins
      show a decrease in abundance. Similar changes are induced by retinal detachment.
      Environmental and genetic perturbations that modulate the RPE response to bright
      light suggest that this response is controlled by the retina. In contrast to the
      response to bright light, the RPE response to retinal detachment overrides these
      modulatory affects.

PMID- 18815273
TI  - Attenuation of neural responses in primary visual cortex during the attentional
      blink.
AB  - Information-processing bottlenecks are characteristic of many cognitive and
      neural systems. One such bottleneck is revealed by tasks in which rapidly
      successive stimulus events must be reported. Here, observers missed the second of
      two visual targets if it occurred within 700 ms of the first [an "attentional
      blink" (AB)], even though this second target could be reported accurately when
      the first item was ignored. Isolating neural responses to such rapid events has
      proven difficult because current magnetic resonance imaging methods rely on
      relatively sluggish changes in the brain's physiological response to sensory
      inputs. Here, we overcame this limitation by presenting successive visual targets
      at different spatial locations, thereby exploiting the retinotopic organization
      of early cortical visual areas to distinguish neural activity associated with
      successive target events. We show that neural activity in primary visual cortex
      is significantly modulated during the AB, and that this activity mirrors
      behavioral measures of target identification accuracy. The findings suggest that
      the neural signature of perceptual suppression during processing of rapidly
      successive stimuli is evident at the earliest stages of cortical sensory
      processing.

PMID- 18815274
TI  - Glycosylated SV2A and SV2B mediate the entry of botulinum neurotoxin E into
      neurons.
AB  - Botulinum neurotoxin E (BoNT/E) can cause paralysis in humans and animals by
      blocking neurotransmitter release from presynaptic nerve terminals. How this
      toxin targets and enters neurons is not known. Here we identified two isoforms of
      the synaptic vesicle protein SV2, SV2A and SV2B, as the protein receptors for
      BoNT/E. BoNT/E failed to enter neurons cultured from SV2A/B knockout mice; entry
      was restored by expressing SV2A or SV2B, but not SV2C. Mice lacking SV2B
      displayed reduced sensitivity to BoNT/E. The fourth luminal domain of SV2A or
      SV2B alone, expressed in chimeric receptors by replacing the extracellular domain
      of the low-density lipoprotein receptor, can restore the binding and entry of
      BoNT/E into neurons lacking SV2A/B. Furthermore, we found disruption of a N
      glycosylation site (N573Q) within the fourth luminal domain of SV2A rendered the
      mutant unable to mediate the entry of BoNT/E and also reduced the entry of
      BoNT/A. Finally, we demonstrate that BoNT/E failed to bind and enter ganglioside
      deficient neurons; entry was rescued by loading exogenous gangliosides into
      neuronal membranes. Together, the data reported here demonstrate that
      glycosylated SV2A and SV2B act in conjunction with gangliosides to mediate the
      entry of BoNT/E into neurons.

PMID- 18815275
TI  - Filamin B serves as a molecular scaffold for type I interferon-induced c-Jun NH2
      terminal kinase signaling pathway.
AB  - Type I interferons (IFNs) activate Janus tyrosine kinase-signal transducer and
      activator of transcription pathway for exerting pleiotropic biological effects,
      including antiviral, antiproliferative, and immunomodulatory responses. Here, we
      demonstrate that filamin B functions as a scaffold that links between activated
      Rac1 and a c-Jun NH(2)-terminal kinase (JNK) cascade module for mediating type I
      IFN signaling. Filamin B interacted with Rac1, mitogen-activated protein kinase
      kinase kinase 1, mitogen-activated protein kinase kinase 4, and JNK. Filamin B
      markedly enhanced IFNalpha-dependent Rac1 activation and the sequential
      activation of the JNK cascade members. Complementation assays using M2 melanoma
      cells revealed that filamin B, but not filamin A, is required for IFNalpha
      dependent activation of JNK. Furthermore, filamin B promoted IFNalpha-induced
      apoptosis, whereas short hairpin RNA-mediated knockdown of filamin B prevented
      it. These results establish a novel function of filamin B as a molecular scaffold
      in the JNK signaling pathway for type I IFN-induced apoptosis, thus providing the
      biological basis for antitumor and antiviral functions of type I IFNs.

PMID- 18815276
TI  - INF1 is a novel microtubule-associated formin.
AB  - Formin proteins, characterized by the presence of conserved formin homology (FH)
      domains, play important roles in cytoskeletal regulation via their abilities to
      nucleate actin filament formation and to interact with multiple other proteins
      involved in cytoskeletal regulation. The C-terminal FH2 domain of formins is key
      for actin filament interactions and has been implicated in playing a role in
      interactions with microtubules. Inverted formin 1 (INF1) is unusual among the
      formin family in having the conserved FH1 and FH2 domains in its N-terminal half,
      with its C-terminal half being composed of a unique polypeptide sequence. In this
      study, we have examined a potential role for INF1 in regulating microtubule
      structure. INF1 associates discretely with microtubules, and this association is
      dependent on a novel C-terminal microtubule-binding domain. INF1 expressed in
      fibroblast cells induced actin stress fiber formation, coalignment of
      microtubules with actin filaments, and the formation of bundled, acetylated
      microtubules. Endogenous INF1 showed an association with acetylated microtubules,
      and knockdown of INF1 resulted in decreased levels of acetylated microtubules.
      Our data suggests a role for INF1 in microtubule modification and potentially in
      coordinating microtubule and F-actin structure.

PMID- 18815277
TI  - Smoothened signaling in vertebrates is facilitated by a G protein-coupled
      receptor kinase.
AB  - Smoothened, a heptahelical membrane protein, functions as the transducer of
      Hedgehog signaling. The kinases that modulate Smoothened have been thoroughly
      analyzed in flies. However, little is known about how phosphorylation affects
      Smoothened in vertebrates, mainly, because the residues, where Smoothened is
      phosphorylated are not conserved from Drosophila to vertebrates. Given its
      molecular architecture, Smoothened signaling is likely to be regulated in a
      manner analogous to G protein-coupled receptors (GPCRs). Previously, it has been
      shown, that arrestins and GPCR kinases, (GRKs) not only desensitize G protein
      dependent receptor signaling but also function as triggers for GPCR trafficking
      and formation of signaling complexes. Here we describe that a GRK contributes to
      Smoothened-mediated signaling in vertebrates. Knockdown of the zebrafish homolog
      of mammalian GRK2/3 results in lowered Hedgehog transcriptional responses,
      impaired muscle development, and neural patterning. Results obtained in zebrafish
      are corroborated both in cell culture, where zGRK2/3 phosphorylates Smoothened
      and promotes Smoothened signal transduction and in mice where deletion of GRK2
      interferes with neural tube patterning. Together, these data suggest that a GRK
      functions as a vertebrate kinase for Smoothened, promoting Hedgehog signal
      transduction during early development.

PMID- 18815278
TI  - Aftiphilin and gamma-synergin are required for secretagogue sensitivity of Weibel
      Palade bodies in endothelial cells.
AB  - Formation of secretory organelles requires the coupling of cargo selection to
      targeting into the correct exocytic pathway. Although the assembly of regulated
      secretory granules is driven in part by selective aggregation and retention of
      content, we recently reported that adaptor protein-1 (AP-1) recruitment of
      clathrin is essential to the initial formation of Weibel-Palade bodies (WPBs) at
      the trans-Golgi network. A selective co-aggregation process might include
      recruitment of components required for targeting to the regulated secretory
      pathway. However, we find that acquisition of the regulated secretory phenotype
      by WPBs in endothelial cells is coupled to but can be separated from formation of
      the distinctive granule core by ablation of the AP-1 effectors aftiphilin and
      gamma-synergin. Their depletion by small interfering RNA leads to WPBs that fail
      to respond to secretagogue and release their content in an unregulated manner. We
      find that these non-responsive WPBs have density, markers of maturation, and
      highly multimerized von Willebrand factor similar to those of wild-type granules.
      Thus, by also recruiting aftiphilin/gamma-synergin in addition to clathrin, AP-1
      coordinates formation of WPBs with their acquisition of a regulated secretory
      phenotype.

PMID- 18815279
TI  - Posttranslational regulation of NF-YA modulates NF-Y transcriptional activity.
AB  - NF-Y binds to CCAAT motifs in the promoter region of a variety of genes involved
      in cell cycle progression. The NF-Y complex comprises three subunits, NF-YA, -YB,
      and -YC, all required for DNA binding. Expression of NF-YA fluctuates during the
      cell cycle and is down-regulated in postmitotic cells, indicating its role as the
      regulatory subunit of the complex. Control of NF-YA accumulation is
      posttranscriptional, NF-YA mRNA being relatively constant. Here we show that the
      levels of NF-YA protein are regulated posttranslationally by ubiquitylation and
      acetylation. A NF-YA protein carrying four mutated lysines in the C-terminal
      domain is more stable than the wild-type form, indicating that these lysines are
      ubiquitylated Two of the lysines are acetylated in vitro by p300, suggesting a
      competition between ubiquitylation and acetylation of overlapping residues.
      Interestingly, overexpression of a degradation-resistant NF-YA protein leads to
      sustained expression of mitotic cyclin complexes and increased cell
      proliferation, indicating that a tight regulation of NF-YA levels contributes to
      regulate NF-Y activity.

PMID- 18815280
TI  - Oxidative folding and assembly with transthyretin are sequential events in the
      biogenesis of retinol binding protein in the endoplasmic reticulum.
AB  - Retinol-binding protein (RBP) is secreted out of the cell in its ligand-bound
      holo-form. The apo-form of RBP is selectively retained within the endoplasmic
      reticulum (ER) by a mechanism that remains unknown. Using isolated microsomal
      system, we have recapitulated the biogenesis of RBP involving its oxidative
      folding and assembly with transthyretin in the ER. In addition to dissecting its
      pathway of disulfide oxidation, we have analyzed association of its early folding
      intermediates with ER-chaperones. Our results show that of the three
      intramolecular disulfides present in RBP (4-160, 70-174, and 120-129) the
      smallest loop (120-129) was most critical for RBP to fold. Its absence caused RBP
      to aggregate into an intermolecular disulfide-linked structure. After acquisition
      of the small loop, formation of one of the two big disulfides (4-160 or 70-174)
      was sufficient for RBP to acquire a folded state. Using cross-linking in intact
      microsomes and sedimentation on sucrose gradients, we show that newly synthesized
      RBP is associated with a complex of chaperones consisting of Grp94, BiP, PDI, and
      calnexin. The complex was constitutively present in the ER, independent of the
      presence of folding substrates. RBP dissociated from this complex coincident with
      the formation of one of the two big disulfide loops, whereas RBP mutant lacking
      both the large disulfides showed persistent association. While highlighting the
      matrix-like characteristics of ER in isolated microsomal system our results
      provide insight into RBP folding and assembly mechanisms that will aid our
      understanding of its complex secretion properties.

PMID- 18815281
TI  - Epstein-Barr virus latent membrane protein 2A exploits Notch1 to alter B-cell
      identity in vivo.
AB  - Expression of latent membrane protein 2 (LMP2A) during B-cell development leads
      to global alterations in gene transcription similar to those seen in Hodgkin Reed
      Sternberg cells of Hodgkin lymphoma (HL). Along with the consistent detection of
      LMP2A in Epstein-Barr virus-associated HL, this implicates a role for LMP2A in
      the pathogenesis of HL. We have shown that LMP2A constitutively activates the
      Notch1 pathway to autoregulate the LMP2A promoter. To determine whether
      constitutive activation of the Notch pathway is important for LMP2A-mediated
      alterations in B-cell development in vivo, TgE-LMP2A-transgenic mice were
      intercrossed with mice expressing loxP-flanked Notch1 genes and Cre recombinase.
      B cells from TgE Notch1(lox/lox)-CD19(+/Cre) mice have an increase in
      immunoglobulin M and CD43 and a decrease in CD5 expression in the bone marrow
      compared with TgE Notch1(lox/lox) mice, indicating the LMP2A signal for
      developmental aberrations is impaired in the absence of Notch1. Real-time reverse
      transcribed polymerase chain reaction analysis reveals that LMP2A requires the
      Notch1 pathway to alter levels of B cell-specific transcription factors, E2A and
      EBF. Interestingly, Notch1 appears to be important for LMP2A-mediated survival in
      low interleukin-7. We propose that LMP2A and the Notch1 pathway may cooperate to
      induce the alterations in B-cell identity seen in Hodgkin Reed-Sternberg cells.

PMID- 18815282
TI  - Curcumin, a cancer chemopreventive and chemotherapeutic agent, is a biologically
      active iron chelator.
AB  - Curcumin is a natural product currently in human clinical trials for a variety of
      neoplastic, preneoplastic, and inflammatory conditions. We previously observed
      that, in cultured cells, curcumin exhibits properties of an iron chelator. To
      test whether the chelator activity of curcumin is sufficient to induce iron
      deficiency in vivo, mice were placed on diets containing graded concentrations of
      both iron and curcumin for 26 weeks. Mice receiving the lowest level of dietary
      iron exhibited borderline iron deficiency, with reductions in spleen and liver
      iron, but little effect on hemoglobin, hematocrit, transferrin saturation, or
      plasma iron. Against this backdrop of subclinical iron deficiency, curcumin
      exerted profound 2 effects on systemic iron, inducing a dose-dependent decline in
      hematocrit, hemoglobin, serum iron, and transferrin saturation, the appearance of
      microcytic anisocytotic red blood cells, and decreases in spleen and liver iron
      content. Curcumin repressed synthesis of hepcidin, a peptide that plays a central
      role in regulation of systemic iron balance. These results demonstrate that
      curcumin has the potential to affect systemic iron metabolism, particularly in a
      setting of subclinical iron deficiency. This may affect the use of curcumin in
      patients with marginal iron stores or those exhibiting the anemia of cancer and
      chronic disease.

PMID- 18815284
TI  - Anti-CD3 prevents factor VIII inhibitor development in hemophilia A mice by a
      regulatory CD4+CD25+-dependent mechanism and by shifting cytokine production to
      favor a Th1 response.
AB  - Non-Fc-receptor binding anti-CD3 Ab therapy, in the setting of several different
      autoimmune disorders, can induce antigen-specific and long-lasting immunologic
      tolerance. Because factor VIII (FVIII) inhibitor formation is the most serious
      treatment-related complication for hemophilia A patients, we tested the efficacy
      of anti-CD3 to prevent FVIII inhibitor formation in hemophilia A BALB/c and
      C57BL/6 mice. A short course of low-dose anti-CD3 significantly increased
      expression of CD25 and the proportion of CD4+CD25+ regulatory T cells in the
      spleen and potently prevented the production of inhibitory and non-neutralizing
      anti-FVIII antibodies in both strains of mouse. Depleting the CD4+CD25+ cells
      during anti-CD3 therapy completely ablated tolerance to FVIII. Further phenotypic
      characterization of regulatory cells in tolerant mice showed a consistently
      higher number of CD4+GITR+ and CD4+FoxP3+ cells in both strains of mice. In
      addition, in tolerant C57BL/6 mice we observed an increase in CD4+CD25+ CTLA-4+
      and CD4+CD25+mTGF-beta1+ cells. Finally, in vitro cytokine profiling demonstrated
      that splenocytes from tolerant BALB/c and C57BL/6 were polarized toward a Th1
      immune response. Taken together, these findings indicate that anti-CD3 induces
      tolerance to FVIII and that the mechanism(s) regulating this response almost
      certainly occurs through the generation of several distinct regulatory T-cell
      lineages and by influencing cytokine production and profile.

PMID- 18815283
TI  - Distinct roles of helper T-cell subsets in a systemic autoimmune disease.
AB  - Imbalance of T-helper cell (Th) differentiation and subsequent cytokine
      dysregulation is implicated in inflammatory and autoimmune diseases. In
      particular, 2 cytokines produced by different Th cell populations, interferon
      gamma (IFN-gamma) and interleukin-17 (IL-17), have been shown to play a critical
      role in autoimmunity. We have examined the roles of these cytokines in a mouse
      model of systemic autoimmunity resulting from the deletion of IL-2 in which
      autoimmune hemolytic anemia (AIHA) is a prominent feature. We demonstrate that,
      in IL-2-knockout (KO) BALB/c mice, elimination of the Th1 cytokine, IFN-gamma,
      delays the development of AIHA. Further, CD4(+) T cells from IL-2/IFN-gamma-KO
      mice produce elevated levels of IL-17 compared with wild-type (WT) and IL-2-KO,
      and these mice eventually develop intestinal inflammation. In contrast,
      elimination of the Th17 cytokine, IL-17, from IL-2-KO mice fails to suppress
      early acute AIHA development. These results suggest that in a systemic autoimmune
      disease with multiple manifestations, Th1 cells drive the early autoantibody
      response and IL-17-producing cells may be responsible for the more chronic tissue
      inflammation.

PMID- 18815285
TI  - Defective synthesis or association of T-cell receptor chains underlies loss of
      surface T-cell receptor-CD3 expression in enteropathy-associated T-cell lymphoma.
AB  - Enteropathy-associated T-cell lymphoma, an often fatal complication of celiac
      disease, can result from expansion of aberrant intraepithelial lymphocytes in
      refractory celiac disease type II (RCD II). Aberrant intraepithelial lymphocytes
      and lymphoma cells are intracellularly CD3epsilon(+) but lack expression of the T
      cell receptor (TCR)-CD3 complex on the cell surface. It is unknown what causes
      the loss of TCR-CD3 expression. We report the isolation of a cell line from an
      RCD II patient with the characteristic phenotype of enteropathy-associated T-cell
      lymphoma. We demonstrate that in this cell line the TCR-alpha and -beta chains as
      well as the CD3gamma, CD3delta, CD3epsilon, and zeta-chains are present
      intracellularly and that assembly of the CD3gammaepsilon, CD3deltaepsilon, and
      zetazeta-dimers is normal. However, dimerization of the TCR chains and proper
      assembly of the TCR-CD3 complex are defective. On introduction of exogenous TCR
      beta chains, but not of TCR-alpha chains, assembly and functional cell surface
      expression of the TCR-CD3 complex were restored. Defective synthesis of both TCR
      chains was found to underlie loss of TCR expression in similar cell lines
      isolated from 2 additional patients. (Pre)malignant transformation in RCD II thus
      correlates with defective synthesis or defective association of the TCR chains,
      resulting in loss of surface TCR-CD3 expression.

PMID- 18815286
TI  - CD44-specific antibody treatment and CD44 deficiency exert distinct effects on
      leukocyte recruitment in experimental arthritis.
AB  - CD44, the leukocyte adhesion receptor for hyaluronan, has been considered a
      therapeutic target on the basis of the robust anti-inflammatory effect of CD44
      specific antibodies in animal models of immune-mediated diseases. However, CD44
      deficiency does not provide substantial protection against inflammation. Using
      intravital video microscopy in a murine model of rheumatoid arthritis, we show
      that CD44 deficiency and anti-CD44 antibody treatment exert disparate effects on
      leukocyte recruitment in inflamed joints. Leukocyte rolling, which is increased
      in CD44-deficient mice, is promptly abrogated in anti-CD44-treated wild-type
      mice. CD44-specific antibodies also trigger platelet deposition on granulocytes
      and subsequent depletion of this leukocyte subset in the circulation. These in
      vivo effects require CD44 cross-linking and are reproducible with an antibody
      against Gr-1, a molecule that, like CD44, is highly expressed on granulocytes.
      Anticoagulant pretreatment, which prevents platelet deposition, mitigates both
      granulocyte depletion and the suppressive effect of CD44-specific antibody on
      joint swelling. Our observations suggest that cross-linking of prominent cell
      surface molecules, such as CD44 or Gr-1, can initiate a rapid self-elimination
      program in granulocytes through engagement of the coagulation system. We conclude
      that the robust anti-inflammatory effect of CD44-specific antibodies in arthritis
      is primarily the result of their ability to trigger granulocyte depletion.

PMID- 18815287
TI  - Prox1 physically and functionally interacts with COUP-TFII to specify lymphatic
      endothelial cell fate.
AB  - Specification of endothelial cell (EC) fate during vascular development is
      controlled by distinct key regulators. While Notch plays an essential role in
      induction of arterial phenotypes, COUP-TFII is required to maintain the venous EC
      identity. Homeodomain transcription factor Prox1 functions to reprogram venous
      ECs to lymphatic endothelial cells (LECs). Here, we report that the venous EC
      fate regulator COUP-TFII is expressed in LECs throughout development and
      physically interacts with Prox1 to form a stable complex in various cell types
      including LECs. We found that COUP-TFII functions as a coregulator of Prox1 to
      control several lineage-specific genes including VEGFR-3, FGFR-3, and neuropilin
      1 and is required along with Prox1 to maintain LEC phenotype. Together, we
      propose that the physical and functional interactions of the 2 proteins
      constitute an essential part in the program specifying LEC fate and may provide
      the molecular basis for the hypothesis of venous EC identity being the
      prerequisite for LEC specification.

PMID- 18815288
TI  - Adhesive activity of Lu glycoproteins is regulated by interaction with spectrin.
AB  - The Lutheran (Lu) and Lu(v13) blood group glycoproteins function as receptors for
      extracellular matrix laminins. Lu and Lu(v13) are linked to the erythrocyte
      cytoskeleton through a direct interaction with spectrin. However, neither the
      molecular basis of the interaction nor its functional consequences have
      previously been delineated. In the present study, we defined the binding motifs
      of Lu and Lu(v13) on spectrin and identified a functional role for this
      interaction. We found that the cytoplasmic domains of both Lu and Lu(v13) bound
      to repeat 4 of the alpha spectrin chain. The interaction of full-length spectrin
      dimer to Lu and Lu(v13) was inhibited by repeat 4 of alpha-spectrin. Further,
      resealing of this repeat peptide into erythrocytes led to weakened Lu
      cytoskeleton interaction as demonstrated by increased detergent extractability of
      Lu. Importantly, disruption of the Lu-spectrin linkage was accompanied by
      enhanced cell adhesion to laminin. We conclude that the interaction of the Lu
      cytoplasmic tail with the cytoskeleton regulates its adhesive receptor function.

PMID- 18815290
TI  - Inherited and acquired variations in the hyaluronan synthase 1 (HAS1) gene may
      contribute to disease progression in multiple myeloma and Waldenstrom
      macroglobulinemia.
AB  - To characterize genetic contributions toward aberrant splicing of the hyaluronan
      synthase 1 (HAS1) gene in multiple myeloma (MM) and Waldenstrom macroglobulinemia
      (WM), we sequenced 3616 bp in HAS1 exons and introns involved in aberrant
      splicing, from 17 patients. We identified a total of 197 HAS1 genetic variations
      (GVs), a range of 3 to 24 GVs/patient, including 87 somatic GVs acquired in
      splicing regions of HAS1. Nearly all newly identified inherited and somatic GVs
      in MM and/or WM were absent from B chronic lymphocytic leukemia, nonmalignant
      disease, and healthy donors. Somatic HAS1 GVs recurred in all hematopoietic cells
      tested, including normal CD34(+) hematopoietic progenitor cells and T cells, or
      as tumor-specific GVs restricted to malignant B and plasma cells. An in vitro
      splicing assay confirmed that HAS1 GVs direct aberrant HAS1 intronic splicing.
      Recurrent somatic GVs may be enriched by strong mutational selection leading to
      MM and/or WM.

PMID- 18815289
TI  - Rapidly proliferating CD44hi peripheral T cells undergo apoptosis and delay
      posttransplantation T-cell reconstitution after allogeneic bone marrow
      transplantation.
AB  - Delayed T-cell recovery is an important complication of allogeneic bone marrow
      transplantation (BMT). We demonstrate in murine models that donor BM-derived T
      cells display increased apoptosis in recipients of allogeneic BMT with or without
      GVHD. Although this apoptosis was associated with a loss of Bcl-2 and Bcl-X(L)
      expression, allogeneic recipients of donor BM deficient in Fas-, tumor necrosis
      factor-related apoptosis-inducing ligand (TRAIL)- or Bax-, or BM-overexpressing
      Bcl-2 or Akt showed no decrease in apoptosis of peripheral donor-derived T cells.
      CD44 expression was associated with an increased percentage of BM-derived
      apoptotic CD4(+) and CD8(+) T cells. Transplantation of RAG-2-eGFP-transgenic BM
      revealed that proliferating eGFP(lo)CD44(hi) donor BM-derived mature T cells were
      more likely to undergo to apoptosis than nondivided eGFP(hi)CD44(lo) recent
      thymic emigrants in the periphery. Finally, experiments using carboxyfluorescein
      succinimidyl ester-labeled T cells adoptively transferred into irradiated
      syngeneic hosts revealed that rapid spontaneous proliferation (as opposed to slow
      homeostatic proliferation) and acquisition of a CD44(hi) phenotype was associated
      with increased apoptosis in T cells. We conclude that apoptosis of newly
      generated donor-derived peripheral T cells after an allogeneic BMT contributes to
      delayed T-cell reconstitution and is associated with CD44 expression and rapid
      spontaneous proliferation by donor BM-derived T cells.

PMID- 18815291
TI  - Focus on antivirally active sulfated polysaccharides: from structure-activity
      analysis to clinical evaluation.
AB  - In recent years, many compounds having potent antiviral activity in cell culture
      have been detected and some of these compounds are currently undergoing either
      preclinical or clinical evaluation. Among these antiviral substances, naturally
      occurring sulfated polysaccharides and those from synthetic origin are
      noteworthy. Recently, several controversies over the molecular structures of
      sulfated polysaccharides, viral glycoproteins, and cell-surface receptors have
      been resolved, and many aspects of their antiviral activity have been elucidated.
      It has become clear that the antiviral properties of sulfated polysaccharides are
      not only a simple function of their charge density and chain length but also
      their detailed structural features. The in vivo efficacy of these compounds
      mostly corresponds to their ability to inhibit the attachment of the virion to
      the host cell surface although in some cases virucidal activity plays an
      additional role. This review summarizes experimental evidence indicating that
      sulfated polysaccharides might become increasingly important in drug development
      for the prevention of sexually transmitted diseases in the near future.

PMID- 18815293
TI  - Estimating in vivo death rates of targets due to CD8 T-cell-mediated killing.
AB  - Despite recent advances in immunology, several key parameters determining virus
      dynamics in infected hosts remain largely unknown. For example, the rate at which
      specific effector and memory CD8 T cells clear virus-infected cells in vivo is
      hardly known for any viral infection. We propose a framework to quantify T-cell
      mediated killing of infected or peptide-pulsed target cells using the widely used
      in vivo cytotoxicity assay. We have reanalyzed recently published data on killing
      of peptide-pulsed splenocytes by cytotoxic T lymphocytes and memory CD8 T cells
      specific to NP396 and GP276 epitopes of lymphocytic choriomeningitis virus (LCMV)
      in the mouse spleen. Because there are so many effector CD8 T cells in spleens of
      mice at the peak of the immune response, NP396- and GP276-pulsed targets are
      estimated to have very short half-lives of 2 and 14 min, respectively. After the
      effector numbers have diminished, i.e., in LCMV-immune mice, the half-lives
      become 48 min and 2.8 h for NP396- and GP276-expressing targets, respectively.
      Analysis of several alternative models demonstrates that the estimates of half
      life times of peptide-pulsed targets are not affected when changes are made in
      the model assumptions. Our report provides a unifying framework to compare
      killing efficacies of CD8 T-cell responses specific to different viral and
      bacterial infections in vivo, which may be used to compare efficacies of various
      cytotoxic-T-lymphocyte-based vaccines.

PMID- 18815292
TI  - Profiling the specificity of neutralizing antibodies in a large panel of plasmas
      from patients chronically infected with human immunodeficiency virus type 1
      subtypes B and C.
AB  - Identifying the viral epitopes targeted by broad neutralizing antibodies (NAbs)
      that sometimes develop in human immunodeficiency virus type 1 (HIV-1)-infected
      subjects should assist in the design of vaccines to elicit similar responses.
      Here, we investigated the activities of a panel of 24 broadly neutralizing
      plasmas from subtype B- and C-infected donors using a series of complementary
      mapping methods, focusing mostly on JR-FL as a prototype subtype B primary
      isolate. Adsorption with gp120 immobilized on beads revealed that an often large
      but variable fraction of plasma neutralization was directed to gp120 and that in
      some cases, neutralization was largely mediated by CD4 binding site (CD4bs) Abs.
      The results of a native polyacrylamide gel electrophoresis assay using JR-FL
      trimers further suggested that half of the subtype B and a smaller fraction of
      subtype C plasmas contained a significant proportion of NAbs directed to the
      CD4bs. Anti-gp41 neutralizing activity was detected in several plasmas of both
      subtypes, but in all but one case, constituted only a minor fraction of the
      overall neutralization activity. Assessment of the activities of the subtype B
      plasmas against chimeric HIV-2 viruses bearing various fragments of the membrane
      proximal external region (MPER) of HIV-1 gp41 revealed mixed patterns, implying
      that MPER neutralization was not dominated by any single specificity akin to
      known MPER-specific monoclonal Abs. V3 and 2G12-like NAbs appeared to make little
      or no contribution to JR-FL neutralization titers. Overall, we observed
      significant titers of anti-CD4bs NAbs in several plasmas, but approximately two
      thirds of the neutralizing activity remained undefined, suggesting the existence
      of NAbs with specificities unlike any characterized to date.

PMID- 18815294
TI  - Phylogenetic analysis of the species Theilovirus: emerging murine and human
      pathogens.
AB  - The Cardiovirus genus of the family Picornaviridae includes two distinct species,
      Encephalomyocarditis virus and Theilovirus. We now report the complete nucleotide
      sequences of three Theiler's murine encephalomyelitis virus (TMEV) strains (TO
      Yale, TOB15, and Vie 415HTR) and of Vilyuisk human encephalomyelitis virus
      (VHEV). This information, together with the recently reported sequences of
      divergent theiloviruses (Theiler's-like rat virus [TRV] and Saffold viruses 1 and
      2 [SAFV-1 and SAFV-2]), enables an updated phylogenetic analysis as well as a
      reexamination of several gene products important in the pathogenesis of this
      emerging group of viruses. In the light of the known neurotropism of TMEV and the
      new human SAFV-1 and SAFV-2, the resulting data suggest the existence of
      theiloviruses that cause human central nervous system infections. Our
      phylogenetic analyses point to the classification of presently known
      theiloviruses into five types: TMEV, VHEV, TRV, SAFV-1, and SAFV-2.

PMID- 18815295
TI  - Evolution of CCR5 use before and during coreceptor switching.
AB  - The envelope gene (env) of human immunodeficiency virus type 1 (HIV-1) undergoes
      rapid divergence from the transmitted sequence and increasing diversification
      during the prolonged course of chronic infection in humans. In about half of
      infected individuals or more, env evolution leads to expansion of the use of
      entry coreceptor from CCR5 alone to CCR5 and CXCR4. The stochastic nature of this
      coreceptor switch is not well explained by host selective forces that should be
      relatively constant between infected individuals. Moreover, differences in the
      incidence of coreceptor switching among different HIV-1 subtypes suggest that
      properties of the evolving virus population drive the switch. We evaluated the
      functional properties of sequential env clones from a patient with evidence of
      coreceptor switching at 5.67 years of infection. We found an abrupt decline in
      the ability of viruses to use CCR5 for entry at this time, manifested by a 1- to
      2-log increase in susceptibility to CCR5 inhibitors and a reduced ability to
      infect cell lines with low CCR5 expression. There was an abnormally rapid 5.4%
      divergence in env sequences from 4.10 to 5.76 years of infection, with the V3 and
      V4/V5 regions showing the greatest divergence and evidence of positive selection.
      These observations suggest that a decline in the fitness of R5 virus populations
      may be one driving force that permits the emergence of R5X4 variants.

PMID- 18815296
TI  - Cellular transcription factors Sp1 and Sp3 suppress varicella-zoster virus origin
      dependent DNA replication.
AB  - The varicella-zoster virus (VZV) origin of DNA replication (oriS) contains a 46
      bp AT-rich palindrome and three consensus binding sites for the VZV origin
      binding protein (OBP) encoded by VZV ORF51. All three OBP binding sites are
      upstream of the palindrome in contrast to the sequence of the herpes simplex
      virus oriS, which has required OBP binding sites upstream and downstream of the
      AT-rich region. We are investigating the roles that sequences downstream of the
      palindrome play in VZV oriS-dependent DNA replication. Computer analysis
      identified two GC boxes, GC box 1 and GC box 2, in the downstream region which
      were predicted to be binding sites for the cellular transcription factor Sp1.
      Electrophoretic mobility shift assay and supershift assays showed that two
      members of the Sp family (Sp1 and Sp3) stably bind to GC box 1, but not to GC box
      2. A predicted binding site for the cellular factor Yin Yang 1 (YY1) that
      overlaps with GC box 2 was also identified. Supershift and mutational analyses
      confirmed the binding of YY1 to this site. Mutation of GC box 1 resulted in loss
      of Sp1 and Sp3 binding and an increase in origin-dependent replication efficiency
      in DpnI replication assays. In contrast, mutation of the YY1 site had a
      statistically insignificant effect. These results suggest a model where origin
      dependent DNA replication and viral transcription are coupled by the binding of
      Sp1 and Sp3 to the downstream region of the VZV replication origin during lytic
      infection. They may also have implications regarding establishment or
      reactivation of viral latency.

PMID- 18815297
TI  - Murine coronaviruses encoding nsp2 at different genomic loci have altered
      replication, protein expression, and localization.
AB  - Partial or complete deletion of several coronavirus nonstructural proteins
      (nsps), including open reading frame 1a (ORF1a)-encoded nsp2, results in viable
      mutant proteins with specific replication defects. It is not known whether
      expression of nsps from alternate locations in the genome can complement
      replication defects. In this report, we show that the murine hepatitis virus nsp2
      sequence was tolerated in ORF1b with an in-frame insertion between nsp13 and
      nsp14 and in place of ORF4. Alternate encoding or duplication of the nsp2 gene
      sequence resulted in differences in nsp2 expression, processing, and
      localization, was neutral or detrimental to replication, and did not complement
      an ORF1a Deltansp2 replication defect. The results suggest that wild-type genomic
      organization and expression of nsps are required for optimal replication.

PMID- 18815298
TI  - Borna disease virus P protein affects neural transmission through interactions
      with gamma-aminobutyric acid receptor-associated protein.
AB  - Borna disease virus (BDV) is one of the infectious agents that causes diseases of
      the central nervous system in a wide range of vertebrate species and, perhaps, in
      humans. The phosphoprotein (P) of BDV, an essential cofactor of virus RNA
      dependent RNA polymerase, is required for virus replication. In this study, we
      identified the gamma-aminobutyric acid receptor-associated protein (GABARAP) with
      functions in neurobiology as one of the viral P protein-interacting cellular
      factors by using an approach of phage display-based protein-protein interaction
      analysis. Direct binding between GABARAP and P protein was confirmed by
      coimmunoprecipitation, protein pull-down, and mammalian two-hybrid analyses.
      GABARAP originally was identified as a linker between the gamma-aminobutyric acid
      receptor (GABAR) and the microtubule to regulate receptor trafficking and plays
      important roles in the regulation of the inhibitory neural transmitter gamma
      aminobutyric acid (GABA). We showed that GABARAP colocalizes with P protein in
      the cells infected with BDV or transfected with the P gene, which resulted in
      shifting the localization of GABARAP from the cytosol to the nucleus. We further
      demonstrated that P protein blocks the trafficking of GABAR, a principal GABA
      gated ion channel that plays important roles in neural transmission, to the
      surface of cells infected with BDV or transfected with the P gene. We proposed
      that during BDV infection, P protein binds to GABARAP, shifts the distribution of
      GABARAP from the cytoplasm to the nucleus, and disrupts the trafficking of GABARs
      to the cell membranes, which may result in the inhibition of GABA-induced
      currents and in the enhancement of hyperactivity and anxiety.

PMID- 18815299
TI  - The proto-oncogene Bcl3, induced by Tax, represses Tax-mediated transcription via
      p300 displacement from the human T-cell leukemia virus type 1 promoter.
AB  - The etiology of human T-cell leukemia virus type 1 (HTLV-1)-induced adult T-cell
      leukemia is linked to the expression of the viral oncoprotein Tax. Although the
      mechanism of retroviral transformation is unknown, Tax interferes with
      fundamental cellular processes, including proliferation and apoptosis, and these
      events may directly link Tax to early steps in malignant progression. In this
      study, we examined the interplay between Tax and the potent proto-oncogene B-cell
      chronic leukemia protein 3 (Bcl3). Bcl3 is a critical regulator of cell survival
      and proliferation and is overexpressed in HTLV-1-infected cells. We found that
      Tax induced Bcl3 expression through stimulation of the NF-kappaB pathway. An
      intronic NF-kappaB binding site within the Bcl3 gene served as the primary target
      of Tax-induced NF-kappaB activation. We next considered the consequence of Bcl3
      overexpression on Tax function. Interestingly, we found that Bcl3 formed a stable
      complex with Tax and that this complex potently inhibited Tax-dependent HTLV-1
      transcription. Importantly, Bcl3 associated with the HTLV-1 promoter in a Tax
      dependent manner and inhibited the binding of the critical cellular coactivator
      p300. The conserved ankyrin repeat domain of Bcl3 mediated both Tax binding and
      inhibition of p300 recruitment to the HTLV-1 promoter. Together, these data
      suggest that Tax-induced Bcl3 overexpression benefits the virus in two important
      ways. First, Bcl3 may promote cell division and thus clonal proliferation of the
      virus. Second, Bcl3 may attenuate virion production, facilitating immune evasion.
      One consequence of this regulatory loop may be Bcl3-induced malignant
      transformation of the host cell.

PMID- 18815300
TI  - Vesicular stomatitis virus matrix protein impairs CD1d-mediated antigen
      presentation through activation of the p38 MAPK pathway.
AB  - Natural killer T (NKT) cells are unique T lymphocytes that recognize CD1d-bound
      lipid antigens and play an important role in both innate and acquired immune
      responses against infectious diseases and tumors. We have already shown that a
      vesicular stomatitis virus (VSV) infection results in the rapid inhibition of
      murine CD1d-mediated antigen presentation to NKT cells. In the present study, it
      was found that the VSV matrix (VSV-M) protein is an important element in this
      decrease in antigen presentation postinfection. The VSV-M protein altered the
      intracellular distribution of murine CD1d molecules, resulting in qualitative
      (but not quantitative) changes in cell surface CD1d expression. The M protein was
      distributed throughout the infected cell, and it was found to activate the
      mitogen-activated protein kinase (MAPK) p38 very early postinfection. Infection
      of CD1d(+) cells with a temperature-sensitive VSV-M mutant at the nonpermissive
      temperature both substantially reversed the inhibition of antigen presentation by
      CD1d and delayed the activation of p38. Thus, the VSV-M protein plays an
      important role in permitting the virus to evade important components of the
      innate immune response by regulating specific MAPK pathways.

PMID- 18815301
TI  - Kaposi's sarcoma-associated herpesvirus disrupts adherens junctions and increases
      endothelial permeability by inducing degradation of VE-cadherin.
AB  - Kaposi's sarcoma (KS) is a vascular tumor of proliferative endothelial cells
      caused by KS-associated herpesvirus (KSHV) infection. Aberrant vascular
      permeability is a hallmark of KS manifested as multifocal edematous skin and
      visceral lesions with dysregulated angiogenesis and vast inflammatory
      infiltrations. In this study, we showed that KSHV infection increased the
      permeability of confluent endothelial monolayers to serum albumin, blood-derived
      cells, KSHV-infected cells, and KSHV virions. KSHV-induced permeability was
      associated with the disruption of adherens junctions and the degradation of
      vascular endothelial cadherin (VE-cadherin) protein. Both the inactivation of
      KSHV virions by UV irradiation and the blockage of de novo protein synthesis with
      cycloheximide failed to reverse the KSHV-induced disruption of adherens
      junctions. However, soluble heparin that blocked KSHV entry into cells completely
      inhibited KSHV-induced permeability. Furthermore, the KSHV-induced degradation of
      VE-cadherin was dose dependent on the internalized virus particles. Together,
      these results indicate that KSHV infection induces vascular permeability by
      inducing VE-cadherin degradation during virus entry into cells. KSHV-induced
      aberrant vascular permeability could facilitate virus spread, promote
      inflammation and angiogenesis, and contribute to the pathogenesis of KSHV-induced
      malignancies.

PMID- 18815302
TI  - Interaction of parvovirus B19 with human erythrocytes alters virus structure and
      cell membrane integrity.
AB  - The unique region of the capsid protein VP1 (VP1u) of B19 virus (B19V) elicits a
      dominant immune response and has a phospholipase A(2) (PLA(2)) activity required
      for the infection. Despite these properties, we have observed that the VP1u
      PLA(2) motif occupies an internal position in the capsid. However, brief exposure
      to increasing temperatures induced a progressive accessibility of the PLA(2)
      motif as well as a proportional increase of the PLA(2) activity. Similarly, upon
      binding on human red blood cells (RBCs), a proportion of the capsids externalized
      the VP1u-PLA(2) motif. Incubation of B19V with RBCs from 17 healthy donors
      resulted in extensive virus attachment ranging between 3,000 and 30,000 virions
      per cell. B19V empty capsids represent an important fraction of the viral
      particles circulating in the blood (30 to 40%) and bind to RBCs in the same way
      as full capsids. The extensive B19V binding to RBCs did not cause direct
      hemolysis but an increased osmotic fragility of the cells by a mechanism
      involving the PLA(2) activity of the exposed VP1u. Analysis of a blood sample
      from an individual with a recent B19V infection revealed that, at this particular
      moment of the infection, the virions circulating in the blood were mostly
      associated to the RBC fraction. However, the RBC-bound B19V was not able to
      infect susceptible cells. These observations indicate that RBCs play a
      significant role during B19V infection by triggering the exposure of the
      immunodominant VP1u including its PLA(2) constituent. On the other hand, the
      early exposure of VP1u might facilitate viral internalization and/or uncoating in
      target cells.

PMID- 18815303
TI  - Epstein-Barr virus BGLF4 kinase induces disassembly of the nuclear lamina to
      facilitate virion production.
AB  - DNA viruses adopt various strategies to modulate the cellular environment for
      efficient genome replication and virion production. Previously, we demonstrated
      that the BGLF4 kinase of Epstein-Barr virus (EBV) induces premature chromosome
      condensation through the activation of condensin and topoisomerase IIalpha (C. P.
      Lee, J. Y. Chen, J. T. Wang, K. Kimura, A. Takemoto, C. C. Lu, and M. R. Chen, J.
      Virol. 81:5166-5180, 2007). In this study, we show that BGLF4 interacts with
      lamin A/C and phosphorylates lamin A protein in vitro. Using a green fluorescent
      protein (GFP)-lamin A system, we found that Ser-22, Ser-390, and Ser-392 of lamin
      A are important for the BGLF4-induced disassembly of the nuclear lamina and the
      EBV reactivation-mediated redistribution of nuclear lamin. Virion production and
      protein levels of two EBV primary envelope proteins, BFRF1 and BFLF2, were
      reduced significantly by the expression of GFP-lamin A(5A), which has five Ser
      residues replaced by Ala at amino acids 22, 390, 392, 652, and 657 of lamin A.
      Our data indicate that BGLF4 kinase phosphorylates lamin A/C to promote the
      reorganization of the nuclear lamina, which then may facilitate the interaction
      of BFRF1 and BFLF2s and subsequent virion maturation. UL kinases of alpha- and
      betaherpesviruses also induce the disassembly of the nuclear lamina through
      similar sites on lamin A/C, suggesting a conserved mechanism for the nuclear
      egress of herpesviruses.

PMID- 18815304
TI  - Cymbidium ringspot virus harnesses RNA silencing to control the accumulation of
      virus parasite satellite RNA.
AB  - Cymbidium ringspot virus (CymRSV) satellite RNA (satRNA) is a parasitic subviral
      RNA replicon that replicates and accumulates at the cost of its helper virus.
      This 621-nucleotide (nt) satRNA species has no sequence similarity to the helper
      virus, except for a 51-nt-long region termed the helper-satellite homology (HSH)
      region, which is essential for satRNA replication. We show that the accumulation
      of satRNA strongly depends on temperature and on the presence of the helper virus
      p19 silencing suppressor protein, suggesting that RNA silencing plays a crucial
      role in satRNA accumulation. We also demonstrate that another member of the
      Tombusvirus genus, Carnation Italian ringspot virus (CIRV), supports satRNA
      accumulation at a higher level than CymRSV. Our results suggest that short
      interfering RNA (siRNA) derived from CymRSV targets satRNA more efficiently than
      siRNA from CIRV, possibly because of the higher sequence similarity between the
      HSH regions of the helper and CIRV satRNAs. RNA silencing sensor RNA carrying the
      putative satRNA target site in the HSH region was efficiently cleaved when
      transiently expressed in CymRSV-infected plants but not in CIRV-infected plants.
      Strikingly, replacing the CymRSV HSH box2 sequence with that of CIRV restores
      satRNA accumulation both at 24 degrees C and in the absence of the p19 suppressor
      protein. These findings demonstrate the extraordinary adaptation of this virus to
      its host in terms of harnessing the antiviral silencing response of the plant to
      control the virus parasite satRNA.

PMID- 18815305
TI  - Clearance of adenovirus by Kupffer cells is mediated by scavenger receptors,
      natural antibodies, and complement.
AB  - Kupffer cells (KCs) rapidly remove intravenously injected adenovirus (Ad) vectors
      from the circulation. A better understanding of the mechanisms involved could
      suggest strategies to improve Ad gene delivery by suppressing or evading KC
      uptake. We recently showed that clearance of Ad type 5 vectors by KCs does not
      involve the interaction of Ad with the well-established Ad receptors, namely,
      integrins or the coxsackievirus and Ad receptor (J. S. Smith, Z. Xu, J. Tian, S.
      C. Stevenson, and A. P. Byrnes, Hum. Gene Ther. 19:547-554, 2008). In the current
      study, we systematically quantified the contributions of various receptors and
      plasma proteins to the clearance of Ad by KCs. We found that scavenger receptors
      are a predominant mechanism for the clearance of Ad by KCs. In addition, we found
      that Ad is opsonized by natural immunoglobulin M antibodies and complement and
      that these opsonins play a contributory role in the clearance of Ad by KCs. We
      also examined additional mechanisms that have been postulated to be involved in
      the clearance of Ad, including the binding of Ad to platelets and vitamin K
      dependent coagulation factors, but we found that neither of these were required
      for the clearance of Ad by KCs.

PMID- 18815306
TI  - The immune evasion paradox: immunoevasins of murine cytomegalovirus enhance
      priming of CD8 T cells by preventing negative feedback regulation.
AB  - Cytomegaloviruses express glycoproteins that interfere with antigen presentation
      to CD8 T cells. Although the molecular modes of action of these "immunoevasins"
      differ between cytomegalovirus species, the convergent biological outcome is an
      inhibition of the recognition of infected cells. In murine cytomegalovirus,
      m152/gp40 retains peptide-loaded major histocompatibility complex class I
      molecules in a cis-Golgi compartment, m06/gp48 mediates their vesicular sorting
      for lysosomal degradation, and m04/gp34, although not an immunoevasin in its own
      right, appears to assist in the concerted action of all three molecules. Using
      the L(d)-restricted IE1 epitope YPHFMPTNL in the BALB/c mouse model as a
      paradigm, we provide here an explanation for the paradox that immunoevasins
      enhance CD8 T-cell priming although they inhibit peptide presentation in infected
      cells. Adaptive immune responses are initiated in the regional lymph node (RLN)
      draining the site of pathogen exposure. In particular for antigens that are not
      virion components, the magnitude of viral gene expression providing the antigens
      is likely a critical parameter in priming efficacy. We have therefore focused on
      the events in the RLN and have related priming to intranodal viral gene
      expression. We show that immunoevasins enhance priming by downmodulating an early
      CD8 T-cell-mediated "negative feedback" control of the infection in the cortical
      region of the RLN, thus supporting the model that immunoevasins improve antigen
      supply for indirect priming by uninfected antigen-presenting cells. As an
      important consequence, these findings predict that deletion of immunoevasin genes
      in a replicative vaccine virus is not a favorable option but may, rather, be
      counterproductive.

PMID- 18815307
TI  - Mutational analysis of cis-acting RNA signals in segment 7 of influenza A virus.
AB  - The genomic viral RNA (vRNA) segments of influenza A virus contain specific
      packaging signals at their termini that overlap the coding regions. To further
      characterize cis-acting signals in segment 7, we introduced synonymous mutations
      into the terminal coding regions. Mutation of codons that are normally highly
      conserved reduced virus growth in embryonated eggs and MDCK cells between 10- and
      1,000-fold compared to that of the wild-type virus, whereas similar alterations
      to nonconserved codons had little effect. In all cases, the growth-impaired
      viruses showed defects in virion assembly and genome packaging. In eggs, nearly
      normal numbers of virus particles that in aggregate contained apparently
      equimolar quantities of the eight segments were formed, but with about fourfold
      less overall vRNA content than wild-type virions, suggesting that, on average,
      fewer than eight segments per particle were packaged. Concomitantly, the
      particle/PFU and segment/PFU ratios of the mutant viruses showed relative
      increases of up to 300-fold, with the behavior of the most defective viruses
      approaching that predicted for random segment packaging. Fluorescent staining of
      infected cells for the nucleoprotein and specific vRNAs confirmed that most
      mutant virus particles did not contain a full genome complement. The specific
      infectivity of the mutant viruses produced by MDCK cells was also reduced, but in
      this system, the mutations also dramatically reduced virion production. Overall,
      we conclude that segment 7 plays a key role in the influenza A virus genome
      packaging process, since mutation of as few as 4 nucleotides can dramatically
      inhibit infectious virus production through disruption of vRNA packaging.

PMID- 18815308
TI  - Role of T cells in virus control and disease after infection with pneumonia virus
      of mice.
AB  - Infection of mice with pneumonia virus of mice (PVM) is used as a natural host
      experimental model for studying the pathogenesis of infection with the closely
      related human respiratory syncytial virus. We analyzed the contribution of T
      cells to virus control and pathology after PVM infection. Control of a sublethal
      infection with PVM strain 15 in C57BL/6 mice was accompanied by a 100-fold
      increase in pulmonary cytotoxic T lymphocytes, 20% of which were specific for
      PVM. T-cell-deficient mice failed to eliminate PVM and became virus carriers in
      the absence of the clinical or histopathological signs of pneumonia that occurred
      after infection of control mice. Mice with limited T-cell numbers did not achieve
      virus control without weight loss, indicating that T-cell-mediated virus control
      was closely linked to immunopathology. Both CD4 and CD8 T cells independently
      contributed to virus elimination and disease. Virus control and disease were
      similar in the absence of perforin, gamma interferon, or tumor necrosis factor
      alpha. Interestingly, disease and mortality after lethal high-dose PVM infection
      were independent of T cells. These data illustrate a key role for T cells in
      control of PVM infection and demonstrate that both T-cell-dependent and 
      independent pathways contribute to disease in a viral dose-dependent fashion.

PMID- 18815309
TI  - Escape from HLA-B*08-restricted CD8 T cells by hepatitis C virus is associated
      with fitness costs.
AB  - The inherent sequence diversity of the hepatitis C virus (HCV) represents a major
      hurdle for the adaptive immune system to control viral replication. Mutational
      escape within targeted CD8 epitopes during acute HCV infection has been well
      documented and is one possible mechanism for T-cell failure. HLA-B*08 was
      recently identified as one HLA class I allele associated with spontaneous
      clearance of HCV replication. Selection of escape mutations in the immunodominant
      HLA-B*08-restricted epitope HSKKKCDEL(1395-1403) was observed during acute
      infection. However, little is known about the impact of escape mutations in this
      epitope on viral replication capacity. Their previously reported reversion back
      toward the consensus residue in patients who do not possess the B*08 allele
      suggests that the consensus sequence in this epitope is advantageous for viral
      replication in the absence of immune pressure. The aim of this study was to
      determine the impact of mutational escape from this immunodominant epitope on
      viral replication. We analyzed it with a patient cohort with chronic HCV genotype
      1b infection and in a single-source outbreak (genotype 1b). Sequence changes in
      this highly conserved region are rare and selected almost exclusively in the
      presence of the HLA-B*08 allele. When tested in the subgenomic replicon (Con1),
      the observed mutations reduce viral replication compared with the prototype
      sequence. The results provide direct evidence that escape mutations in this
      epitope are associated with fitness costs and that the antiviral effect of HLA
      B*08-restricted T cells is sufficiently strong to force the virus to adopt a
      relatively unfavorable sequence.

PMID- 18815310
TI  - Human cytomegalovirus glycoproteins gB and gH/gL mediate epithelial cell-cell
      fusion when expressed either in cis or in trans.
AB  - Herpesviruses use a cascade of interactions with different cell surface molecules
      to gain entry into cells. In many cases, this involves binding to abundant
      glycosaminoglycans or integrins followed by interactions with more limited cell
      surface proteins, leading to fusion with cellular membranes. Human
      cytomegalovirus (HCMV) has the ability to infect a wide variety of human cell
      types in vivo. However, very little is known about which HCMV glycoproteins
      mediate entry into various cell types, including relevant epithelial and
      endothelial cells. For other herpesviruses, studies of cell-cell fusion induced
      by viral proteins have provided substantial information about late stages of
      entry. In this report, we describe the fusion of epithelial, endothelial,
      microglial, and fibroblast cells in which HCMV gB and gH/gL were expressed from
      nonreplicating adenovirus vectors. Fusion frequently involved the majority of
      cells, and gB and gH/gL were both necessary and sufficient for fusion, whereas no
      fusion occurred when either glycoprotein was omitted. Coexpression of UL128,
      UL130, and UL131 did not enhance fusion. We concluded that the HCMV core fusion
      machinery consists of gB and gH/gL. Coimmunoprecipitation indicated that HCMV gB
      and gH/gL can interact. Importantly, expression of gB and gH/gL in trans (gB
      expressing cells mixed with other gH/gL-expressing cells) resulted in substantial
      fusion. We believe that this is the first description of a multicomponent viral
      fusion machine that can be split between cells. If gB and gH/gL must interact for
      fusion, then these molecules must reach across the space between apposing cells.
      Expression of gB and gH/gL in trans with different cell types revealed surface
      molecules that are required for fusion on HCMV-permissive cells but not on
      nonpermissive cells.

PMID- 18815311
TI  - Crystal structure and carbohydrate analysis of Nipah virus attachment
      glycoprotein: a template for antiviral and vaccine design.
AB  - Two members of the paramyxovirus family, Nipah virus (NiV) and Hendra virus
      (HeV), are recent additions to a growing number of agents of emergent diseases
      which use bats as a natural host. Identification of ephrin-B2 and ephrin-B3 as
      cellular receptors for these viruses has enabled the development of
      immunotherapeutic reagents which prevent virus attachment and subsequent fusion.
      Here we present the structural analysis of the protein and carbohydrate
      components of the unbound viral attachment glycoprotein of NiV glycoprotein (NiV
      G) at a 2.2-A resolution. Comparison with its ephrin-B2-bound form reveals that
      conformational changes within the envelope glycoprotein are required to achieve
      viral attachment. Structural differences are particularly pronounced in the 579
      590 loop, a major component of the ephrin binding surface. In addition, the 236
      245 loop is rather disordered in the unbound structure. We extend our structural
      characterization of NiV-G with mass spectrometric analysis of the carbohydrate
      moieties. We demonstrate that NiV-G is largely devoid of the oligomannose-type
      glycans that in viruses such as human immunodeficiency virus type 1 and Ebola
      virus influence viral tropism and the host immune response. Nevertheless, we find
      putative ligands for the endothelial cell lectin, LSECtin. Finally, by mapping
      structural conservation and glycosylation site positions from other members of
      the paramyxovirus family, we suggest the molecular surface involved in
      oligomerization. These results suggest possible pathways of virus-host
      interaction and strategies for the optimization of recombinant vaccines.

PMID- 18815312
TI  - Compatibility among polymerase subunit proteins is a restricting factor in
      reassortment between equine H7N7 and human H3N2 influenza viruses.
AB  - Reassortment is an important driving force for influenza virus evolution, and a
      better understanding of the factors that affect this process could improve our
      ability to respond to future influenza pandemics and epidemics. To identify
      factors that restrict the generation of reassortant viruses, we cotransfected
      human embryonic kidney cells with plasmids for the synthesis of viral RNAs of
      both A/equine/Prague/1/56 (Prague; H7N7) and A/Yokohama/2017/03 (Yokohama; H3N2)
      viruses together with the supporting protein expression plasmids. Of the possible
      256 genotypes, we identified 29 genotypes in 120 randomly plaque-picked
      reassortants examined. Analyses of these reassortants suggested that the
      formation of functional ribonucleoprotein (RNP) complexes was a restricting
      factor, a finding that correlated with the activities of RNP complexes composed
      of different combinations of the proteins from the two viruses, as measured in a
      minigenome assay. For at least one nonfunctional RNP complex (i.e., Prague PB2,
      Prague PB1, Yokohama PA, and Prague NP), the lack of activity was due to the
      inability of the three polymerase subunit proteins to form a heterotrimer.
      Adaptation of viruses possessing a gene encoding a chimera of the PA proteins of
      the two viruses and the remaining genes from Prague virus resulted in
      compensatory mutations in the PB2 and/or PA protein. These results indicate
      substantial incompatibility among the gene products of the two test viruses, a
      critical role for the RNP complex in the generation of reassortant viruses, and a
      functional interaction of PB2 and PA.

PMID- 18815313
TI  - Equine herpesvirus 1 entry via endocytosis is facilitated by alphaV integrins and
      an RSD motif in glycoprotein D.
AB  - Equine herpesvirus 1 (EHV-1) is a member of the Alphaherpesvirinae, and its broad
      tissue tropism suggests that EHV-1 may use multiple receptors to initiate virus
      entry. EHV-1 entry was thought to occur exclusively through fusion at the plasma
      membrane, but recently entry via the endocytic/phagocytic pathway was reported
      for Chinese hamster ovary cells (CHO-K1 cells). Here we show that cellular
      integrins, and more specifically those recognizing RGD motifs such as
      alphaVbeta5, are important during the early steps of EHV-1 entry via endocytosis
      in CHO-K1 cells. Moreover, mutational analysis revealed that an RSD motif in the
      EHV-1 envelope glycoprotein D (gD) is critical for entry via endocytosis. In
      addition, we show that EHV-1 enters peripheral blood mononuclear cells
      predominantly via the endocytic pathway, whereas in equine endothelial cells
      entry occurs mainly via fusion at the plasma membrane. Taken together, the data
      in this study provide evidence that EHV-1 entry via endocytosis is triggered by
      the interaction between cellular integrins and the RSD motif present in gD and,
      moreover, that EHV-1 uses different cellular entry pathways to infect important
      target cell populations of its natural host.

PMID- 18815315
TI  - Critical appraisal of cost-effectiveness and cost-utility studies in health care.

PMID- 18815316
TI  - Evidence-based practice targets the individual patient. Part 1: how clinicians
      can use study results to determine optimal individual care.

PMID- 18815317
TI  - Review: home-made and commercial spacers did not differ for delivery of inhaled
      beta2 agonists in children with asthma or wheezing.

PMID- 18815318
TI  - A needle-free powder lignocaine delivery system reduced the pain of venipuncture
      in children.

PMID- 18815319
TI  - Topical aqueous 2% lignocaine eardrops reduced ear pain in children with acute
      otitis media.

PMID- 18815320
TI  - Review: contraceptive patch and vaginal ring are as effective as oral
      contraceptives.

PMID- 18815321
TI  - Review: evidence on the effectiveness of interventions to improve patient
      adherence to prescribed medications is limited.

PMID- 18815314
TI  - Cellular and molecular basis of deiodinase-regulated thyroid hormone signaling.
AB  - The iodothyronine deiodinases initiate or terminate thyroid hormone action and
      therefore are critical for the biological effects mediated by thyroid hormone.
      Over the years, research has focused on their role in preserving serum levels of
      the biologically active molecule T(3) during iodine deficiency. More recently, a
      fascinating new role of these enzymes has been unveiled. The activating
      deiodinase (D2) and the inactivating deiodinase (D3) can locally increase or
      decrease thyroid hormone signaling in a tissue- and temporal-specific fashion,
      independent of changes in thyroid hormone serum concentrations. This mechanism is
      particularly relevant because deiodinase expression can be modulated by a wide
      variety of endogenous signaling molecules such as sonic hedgehog, nuclear factor
      kappaB, growth factors, bile acids, hypoxia-inducible factor-1alpha, as well as a
      growing number of xenobiotic substances. In light of these findings, it seems
      clear that deiodinases play a much broader role than once thought, with great
      ramifications for the control of thyroid hormone signaling during vertebrate
      development and metamorphosis, as well as injury response, tissue repair,
      hypothalamic function, and energy homeostasis in adults.

PMID- 18815322
TI  - Review: screening or case-finding questionnaires used alone are not effective for
      management of depression.

PMID- 18815323
TI  - Review: preprocedure information, breast cushions, and patient-controlled breast
      compression reduce mammography pain.

PMID- 18815324
TI  - Review: reflexology improved urinary symptoms in multiple sclerosis but was not
      effective for other outcomes in various conditions.

PMID- 18815325
TI  - An automated external defibrillator in the home did not reduce all-cause
      mortality in patients at risk of cardiac arrest.

PMID- 18815326
TI  - Review: some interventions may reduce catheter-related bloodstream infections and
      colonisation in the ICU.

PMID- 18815327
TI  - Review: evidence of the effectiveness of hydrocolloids for healing pressure
      ulcers is limited.

PMID- 18815328
TI  - Negative pressure wound therapy promoted healing of diabetic foot ulcers more
      than advanced moist wound therapy.

PMID- 18815329
TI  - Review: low-molecular-weight heparin prevented recurrent VTE more than oral
      anticoagulants in patients with cancer.

PMID- 18815330
TI  - Review: walking aids, chest-wall vibration, and neuroelectrical muscle
      stimulation relieve breathlessness in COPD.

PMID- 18815331
TI  - Automatic stop orders reduced duration of indwelling urinary catheterisation in
      hospital.

PMID- 18815332
TI  - A multifactorial intervention did not prevent falls or fractures in elderly
      patients during short hospital stays.

PMID- 18815333
TI  - Review: simple questions and clinical tests are moderately useful for diagnosing
      urinary incontinence.

PMID- 18815334
TI  - Chorioamnionitis, gestational age, male sex, birth weight, and illness severity
      predicted positive autism screening scores in very-low-birth-weight preterm
      infants.

PMID- 18815335
TI  - Enalapril and captopril increased mortality compared with ramipril in elderly
      patients with heart failure.

PMID- 18815336
TI  - Protocol-directed sedation did not reduce duration of mechanical ventilation or
      hospital stay in ICU patients.

PMID- 18815337
TI  - In teenagers with diabetes, transition toward autonomy in self-management
      involved growth in self-reliance and support from others.

PMID- 18815338
TI  - 4 themes described the experiences of patients before, during, and immediately
      after awake craniotomy.

PMID- 18815339
TI  - Many patients with coronary heart disease believed that stress and lifestyle
      factors caused their illness.

PMID- 18815340
TI  - Patients with terminal illness and their healthcare providers preferred a dosed
      and gradual process of truth-telling.

PMID- 18815341
TI  - Transient enhancement of spike-evoked calcium signaling by a serotonergic
      interneuron.
AB  - Enhancement of presynaptic Ca(2+) signals is widely recognized as a potential
      mechanism for heterosynaptic potentiation of neurotransmitter release. Here we
      show that stimulation of a serotonergic interneuron increased spike-evoked Ca(2+)
      in a manner consistent with its neuromodulatory effect on synaptic transmission.
      In the gastropod mollusk, Tritonia diomedea, stimulation of a serotonergic dorsal
      swim interneuron (DSI) at physiological rates heterosynaptically enhances the
      strength of output synapses made by another swim interneuron, C2, onto neurons in
      the pedal ganglion. Using intracellular electrophysiological recording combined
      with real-time confocal imaging of C2 (loaded with Oregon Green Bapta 1), it was
      determined that DSI stimulation increases the amplitude of spike-evoked Ca(2+)
      signals in C2 without altering basal Ca(2+) signals. This neuromodulatory action
      was restricted to distal neurites of C2 where synapses with pedal neurons are
      located. The effect of DSI stimulation on C2 spike-evoked Ca(2+) signals
      resembled DSI heterosynaptic enhancement of C2 synapses in several measures: both
      decayed within 15 s, both were abolished by the serotonin receptor antagonist,
      methysergide, and both were independent of DSI's depolarizing actions on C2. A
      brief puff of serotonin could mimic the enhancement of spike-evoked Ca(2+)
      signals in the distal neurites of C2, but larger puffs or bath-applied serotonin
      elicited nonphysiological effects. These results suggest that DSI heterosynaptic
      enhancement of C2 synaptic strength may be mediated by a local enhancement of
      spike-evoked Ca(2+) signals in the distal neurites of C2.

PMID- 18815342
TI  - G protein betagamma subunits modulate the number and nature of exocytotic fusion
      events in adrenal chromaffin cells independent of calcium entry.
AB  - G-protein-coupled receptors (GPCR) play important roles in controlling
      neurotransmitter and hormone release. Inhibition of voltage-gated Ca(2+) channels
      (Ca(2+) channels) by G protein betagamma subunits (Gbetagamma) is one prominent
      mechanism, but there is evidence for additional effects distinct from those on
      calcium entry. However, relatively few studies have investigated the Ca(2+)
      channel-independent effects of Gbetagamma on transmitter release, so the impact
      of this mechanism remains unclear. We used carbon fiber amperometry to analyze
      catecholamine release from individual vesicles in bovine adrenal chromaffin
      cells, a widely used neurosecretory model. To bypass the effects of Gbetagamma on
      Ca(2+) entry, we stimulated secretion using ionomycin (a Ca(2+) ionophore) or
      direct intracellular application of Ca(2+) through a patch pipette. Activation of
      endogenous GPCR or transient transfection with exogenous Gbetagamma significantly
      reduced the number of amperometric spikes (the number of vesicular fusion
      events). The charge ("quantal size") and amplitude of the amperometric spikes
      were also significantly reduced by GPCR/Gbetagamma. We conclude that independent
      from effects on calcium entry, Gbetagamma can regulate both the number of
      vesicles that undergo exocytosis and the amount of catecholamine released per
      fusion event. We discuss possible mechanisms by which Gbetagamma might exert
      these novel effects including interaction with the soluble N-ethylmaleimide
      sensitive factor attachment protein receptor (SNARE) complex.

PMID- 18815343
TI  - Selective spike propagation in the central processes of an invertebrate neuron.
AB  - Within a neuron, spike propagation can occur in a complex manner, with spikes
      propagating into some processes but not others. We study this phenomenon in an
      experimentally advantageous mechanoafferent in Aplysia, neuron B21. B21 has two
      processes within the CNS. One is ipsilateral to the soma and is referred to as
      the lateral process. The second travels into the contralateral hemiganglion and
      is referred to as the contralateral process. Previously we characterized spike
      propagation to the lateral process, which is an output region that contacts
      follower motor neurons. Spikes fail to actively propagate to the lateral process
      when B21 is peripherally activated at its resting potential. This propagation
      failure can be relieved if the medial regions of B21 are centrally depolarized
      during peripheral activation. This study examines spike propagation to the
      contralateral process. We show that, unlike the lateral process, active spike
      propagation in the contralateral process occurs when B21 is peripherally
      activated at its resting membrane potential. Thus spike propagation occurs
      selectively, favoring the contralateral process. Interestingly, the contralateral
      process of one B21 is immediately adjacent to the medial region of the
      bilaterally symmetrical cell. The B21 neurons are electrically coupled,
      suggesting that spikes propagating in the contralateral process of one cell could
      modify propagation in the sister neuron. Consistent with this idea, we show that
      lateral process propagation failures observed when a single B21 is peripherally
      activated can be relieved by central coactivation of the contralateral cell.
      These results imply that stimuli that coactivate the B21 neurons bilaterally are
      more apt to generate afferent activity that is transmitted to followers than
      stimuli that activate one cell.

PMID- 18815344
TI  - Speed and temperature dependences of mechanotransduction in afferent fibers
      recorded from the mouse saphenous nerve.
AB  - Here we have systematically characterized the stimulus response properties of
      mechanosensitive sensory fibers in the mouse saphenous nerve. We tested
      mechanoreceptors and nociceptors with defined displacement stimuli of varying
      amplitude and velocity. For each sensory afferent investigated we measured the
      mechanical latency, which is the delay between the onset of a ramp displacement
      and the first evoked spike, corrected for conduction delay. Mechanical latency
      plotted as a function of stimulus strength was very characteristic for each
      receptor type and was very short for rapidly adapting mechanoreceptors (<11 ms)
      but very long in myelinated and unmyelinated nociceptors (49-114 ms). Increasing
      the stimulus speed decreased mechanical latency in all receptor types with the
      notable exception of C-fiber nociceptors, in which mean mechanical latency was
      not reduced less, similar100 ms, even with very fast ramp stimuli (2,945
      microm/s). We examined stimulus response functions and mechanical latency at two
      different temperatures (24 and 32 degrees C) and found that stimulus response
      properties of almost all mechanoreceptors were not altered in this range. A
      notable exception to this rule was found for C-fibers in which mechanical latency
      was substantially increased and stimulus response functions decreased at lower
      temperatures. We calculated Q(10) values for mechanical latency in C-fibers to be
      5.1; in contrast, the Q(10) value for conduction velocity for the same fibers was
      1.4. Finally, we examined the effects of short-term inflammation (2-6 h) induced
      by carrageenan on nociceptor and mechanoreceptor sensitivity. We did not detect
      robust changes in mechanical latency or stimulus response functions after
      inflammation that might have reflected mechanical sensitization under the
      conditions tested.

PMID- 18815345
TI  - High-resolution three-dimensional microelectrode brain mapping using stereo
      microfocal X-ray imaging.
AB  - Much of our knowledge of brain function has been gleaned from studies using
      microelectrodes to characterize the response properties of individual neurons in
      vivo. However, because it is difficult to accurately determine the location of a
      microelectrode tip within the brain, it is impossible to systematically map the
      fine three-dimensional spatial organization of many brain areas, especially in
      deep structures. Here, we present a practical method based on digital stereo
      microfocal X-ray imaging that makes it possible to estimate the three-dimensional
      position of each and every microelectrode recording site in "real time" during
      experimental sessions. We determined the system's ex vivo localization accuracy
      to be better than 50 microm, and we show how we have used this method to
      coregister hundreds of deep-brain microelectrode recordings in monkeys to a
      common frame of reference with median error of <150 microm. We further show how
      we can coregister those sites with magnetic resonance images (MRIs), allowing for
      comparison with anatomy, and laying the groundwork for more detailed
      electrophysiology/functional MRI comparison. Minimally, this method allows one to
      marry the single-cell specificity of microelectrode recording with the spatial
      mapping abilities of imaging techniques; furthermore, it has the potential of
      yielding fundamentally new kinds of high-resolution maps of brain function.

PMID- 18815346
TI  - Opioid receptors on bulbospinal respiratory neurons are not activated during
      neuronal depression by clinically relevant opioid concentrations.
AB  - Opioids depress the activity of brain stem respiratory-related neurons, but it is
      not resolved whether the mechanism at clinical concentrations consists of direct
      neuronal effects or network effects. We performed extracellular recordings of
      discharge activity of single respiratory neurons in the caudal ventral
      respiratory group of decerebrate dogs, which were premotor neurons with a
      likelihood of 90%. We used multibarrel glass microelectrodes, which allowed
      concomitant highly localized picoejection of opioid receptor agonists or
      antagonists onto the neuron. Picoejection of the mu receptor agonist [d-Ala(2), N
      Me-phe(4), gly-ol(5)]-enkephalin (DAMGO, 1 mM) decreased the peak discharge
      frequency (mean +/- SD) of expiratory neurons to 68 +/- 22% (n = 12), the
      delta(1) agonist d-Pen(2,5)-enkephalin (DPDPE, 1 mM) to 95 +/- 11% (n = 15), and
      delta(2) receptor agonist [d-Ala(2)] deltorphin-II to 86 +/- 17% (1 mM, n = 15).
      The corresponding values for inspiratory neurons were: 64 +/- 12% (n = 11), 48 +/
      30% (n = 12), and 75 +/- 15% (n = 11), respectively. Naloxone fully reversed
      these effects. Picoejection of morphine (0.01-1 mM) depressed most neurons in a
      concentration dependent fashion to maximally 63% (n = 27). Picoejection of
      remifentanil (240-480 nM) did not cause any significant depression of inspiratory
      (n = 11) or expiratory neurons (n = 9). 4. Intravenous remifentanil (0.2-0.6
      microg.kg(-1).min(-1)) decreased neuronal peak discharge frequency to 60 +/- 12%
      (inspiratory, n = 7) and 58 +/- 11% (expiratory, n = 11). However, local
      picoejection of naloxone did not reverse the neuronal depression. Our data
      suggest that mu, delta(1), and delta(2) receptors are present on canine
      respiratory premotor neurons. Clinical concentrations of morphine and
      remifentanil caused no local depression. This lack of effect and the inability of
      local naloxone to reverse the neuronal depression by intravenous remifentanil
      suggest that clinical concentrations of opioids produce their depressive effects
      on mechanisms upstream from respiratory bulbospinal premotor neurons.

PMID- 18815347
TI  - Conductances mediating intrinsic theta-frequency membrane potential oscillations
      in layer II parasubicular neurons.
AB  - Ionic conductances that generate membrane potential oscillations in neurons of
      layer II of the parasubiculum were studied using whole cell current-clamp
      recordings in horizontal slices from the rat brain. Blockade of ionotropic
      glutamate and GABA synaptic transmission did not reduce the power of the
      oscillations, indicating that oscillations are not dependent on synaptic inputs.
      Oscillations were eliminated when cells were hyperpolarized 6-10 mV below spike
      threshold, indicating that they are mediated by voltage-dependent conductances.
      Application of TTX completely eliminated oscillations, suggesting that Na(+)
      currents are required for the generation of the oscillations. Oscillations were
      not reduced by blocking Ca(2+) currents with Cd(2+) or Ca(2+)-free artificial
      cerebrospinal fluid, or by blocking K(+) conductances with either 50 microM or 5
      mM 4-aminopyridine (4-AP), 30 mM tetraethylammonium (TEA), or Ba(2+)(1-2 mM).
      Oscillations also persisted during blockade of the muscarinic-dependent K(+)
      current, I(M), using the selective antagonist XE-991 (10 microM). However,
      oscillations were significantly attenuated by blocking the hyperpolarization
      activated cationic current I(h) with Cs(+) and were almost completely blocked by
      the more potent I(h) blocker ZD7288 (100 microM). Intrinsic membrane potential
      oscillations in neurons of layer II of the parasubiculum are therefore likely
      driven by an interaction between an inward persistent Na(+) current and time
      dependent deactivation of I(h). These voltage-dependent conductances provide a
      mechanism for the generation of membrane potential oscillations that can help
      support rhythmic network activity within the parasubiculum during theta-related
      behaviors.

PMID- 18815348
TI  - Delayed synaptic transmission in Drosophila cacophonynull embryos.
AB  - Ca(2+) influx through the Drosophila N-type Ca(2+) channel, encoded by cacophony
      (cac), triggers fast synaptic transmission. We now ask whether the cac Ca(2+)
      channel is the Ca(2+) channel solely dedicated for fast synaptic transmission.
      Because the cac(null) mutation is lethal, we used cac(null) embryos to address
      this question. At the neuromuscular junction in HL3 solution, no fast synchronous
      synaptic transmission was detected on nerve stimulation. When the wild-type cac
      gene was introduced in the cac(null) background, fast synaptic transmission
      recovered. However, even in cac(null) embryos, nerve stimulation infrequently
      induced delayed synaptic events in the minority of cells in 1.5 mM [Ca(2+)](e)
      and in the majority of cells in 5 mM [Ca(2+)](e). The number of delayed quantal
      events per stimulus was greater in 5 mM [Ca(2+)](e) than in 1.5 mM. Thus the
      delayed release is [Ca(2+)](e) dependent. Plectreurys toxin II (PLTXII) (10 nM; a
      spider toxin analog) depressed the frequency of delayed events, suggesting that
      voltage-gated Ca(2+) channels, other than cac Ca(2+) channels, are contributing
      to them. However, delayed events were not affected by 50 microM La(3+). The
      frequency of miniature synaptic currents in cac(null) embryos was approximately
      1/2 of control, whereas in high K(+) solutions, it was approximately 1/135. The
      hypertonicity response was approximately 1/10 of control. These findings indicate
      that the number of release-ready vesicles is smaller in cac(null) embryos. Taken
      together, the cac Ca(2+) channel is indispensable for fast synaptic transmission
      in normal conditions, and another type of Ca(2+) channel, the non-cac, PLTXII
      sensitive Ca(2+) channel, is contributing to delayed release in cac(null)
      embryos.

PMID- 18815349
TI  - Control of predictive error correction during a saccadic double-step task.
AB  - We explored the nature of control during error correction using a modified
      saccadic double-step task in which subjects cancelled the initial saccade to the
      first target and redirected gaze to a second target. Failure to inhibit was
      associated with a quick corrective saccade, suggesting that errors and
      corrections may be planned concurrently. However, because saccade programming
      constitutes a visual and a motor stage of preparation, the extent to which
      parallel processing occurs in anticipation of the error is not known. To estimate
      the time course of error correction, a triple-step condition was introduced that
      displaced the second target during the error. In these trials, corrective
      saccades directed at the location of the target prior to the third step suggest
      motor preparation of the corrective saccade in parallel with the error. To
      estimate the time course of motor preparation of the corrective saccade, further,
      we used an accumulator model (LATER) to fit the reaction times to the triple-step
      stimuli; the best-fit data revealed that the onset of correction could occur even
      before the start of the error. The estimated start of motor correction was also
      observed to be delayed as target step delay decreased, suggesting a form of
      interference between concurrent motor programs. Taken together we interpret these
      results to indicate that predictive error correction may occur concurrently while
      the oculomotor system is trying to inhibit an unwanted movement and suggest how
      inhibitory control and error correction may interact to enable goal-directed
      behaviors.

PMID- 18815350
TI  - A cerebellar deficit in sensorimotor prediction explains movement timing
      variability.
AB  - A popular theory is that the cerebellum functions as a timer for clocking motor
      events (e.g., initiation, termination). Consistent with this idea, cerebellar
      patients have been reported to show greater deficits during hand movements that
      repeatedly start and stop (i.e., discontinuous movements) compared with
      continuous hand movements. Yet, this finding could potentially be explained by an
      alternate theory in which the cerebellum acts as an internal model of limb
      mechanics. We tested whether a timing or internal model hypothesis best explains
      results from a circle-drawing task, where individuals trace a circle with the
      hand at a desired tempo. We first attempted to replicate prior results showing
      greater impairment for discontinuous versus continuous circling movements, and
      then asked whether we could improve patient performance by reducing demands in
      each domain. First, we slowed the movement down to reduce the need to predict and
      compensate for limb dynamics. Second, we supplied external timing information to
      reduce the need for an internal event timer. Results showed that we did not
      replicate the previous findings-cerebellar patients were impaired in both
      discontinuous and continuous movements. Slowing the movement improved cerebellar
      performance to near control values. The addition of an external visual timing
      signal paradoxically worsened timing deficits rather than mitigating them. One
      interpretation of these combined results is that the cerebellum is indeed
      functioning as an internal model and is needed to make appropriate predictions
      for movement initiation and termination.

PMID- 18815351
TI  - Involvement of ST1B subfamily of cytosolic sulfotransferase in kynurenine
      metabolism to form natriuretic xanthurenic acid sulfate.
AB  - Natriuretic substances are a group of molecules affecting sodium homeostasis in
      the body. Recently, two new molecules having natriuresis effects, xanthurenic
      acid 8-O-beta-d-glucoside and xanthurenic acid 8-O-sulfate (XA sulfate), have
      been isolated from human urine. In the present study, we have investigated the
      sulfation of xanthurenic acid (XA) in mouse tissues to assess the contribution of
      specific sulfotransferases (STs) to the reaction. Cytosols from tissues of both
      sexes of C57BL/6N mice (liver, stomach, jejunum, colon, and kidney) were capable
      of forming XA sulfate, with various K(m) values. Jejunum cytosol showed the
      lowest K(m) value, and its V(max)/K(m) value was much greater than those of other
      tissues. The kinetic analyses with recombinant mouse (m) STs (Sult1a1, Sult1b1,
      Sult1c2, and Sult1d1) showed the lowest K(m) value for mSult1b1, and the value
      was comparable with that for jejunum cytosol. The highest expression of mSult1b1
      in small intestine was confirmed at the mRNA and protein levels. mSult1b1 is thus
      suggested as a major enzyme responsible for XA sulfation in jejunum. Similar to
      mSult1b1, human SULT1B1 and rat Sult1b1 mediated XA sulfation efficiently. Thus,
      XA is likely to be an endogenous substrate for ST1B members. In contrast to XA,
      an XA-related compound, kynurenic acid strongly inhibited mSult1b1-mediated
      sulfations, with IC(50) values at a micromolar range. These results indicate the
      functional role of ST1B subfamily of ST in XA sulfate formation in the body.

PMID- 18815353
TI  - Abstracts of the College of Emergency Medicine and the Irish Association for
      Emergency Medicine Autumn Meeting. September 24-25, 2008.

PMID- 18815352
TI  - Inhibition of soluble epoxide hydrolase does not protect against endotoxin
      mediated hepatic inflammation.
AB  - Epoxyeicosatrienoic acids (EETs) are derived from cytochrome P450-catalyzed
      epoxygenation of arachidonic acid and have emerged as important mediators of
      numerous biological effects. The major elimination pathway for EETs is through
      soluble epoxide hydrolase (sEH)-catalyzed metabolism to dihydroxyeicosatrienoic
      acids (DHETs). Based on previous studies showing that EETs have anti-inflammatory
      effects, we hypothesized that chronic inhibition of sEH would attenuate a
      lipopolysaccharide (LPS)-induced inflammatory response in vivo. Continuous dosing
      of the sEH inhibitors 12-(3-adamantan-1-ylureido)-dodecanoic acid (AUDA), a
      polyethylene glycol ester of AUDA, and 1-adamantan-1-yl-3-(5-(2-(2
      ethoxyethoxy)ethoxy)-pentyl)urea resulted in robust exposure to the inhibitor and
      target engagement, as evidenced by significant increases in plasma EET/DHET
      ratios following 6 days of inhibitor treatment. However, sEH inhibitor treatment
      was not associated with an attenuation of LPS-induced inflammatory gene
      expression in the liver, and AUDA did not protect from LPS-induced neutrophil
      infiltration. Furthermore, Ephx2-/-mice that lack sEH expression and have
      significantly increased plasma EET/DHET ratios were not protected from LPS
      induced inflammatory gene expression or neutrophil accumulation in the liver. LPS
      did have an effect on sEH expression and function, as evident from a significant
      down-regulation of Ephx2 mRNA and a significant shift in plasma EET/DHET ratios 4
      h after LPS treatment. In conclusion, there was no evidence that increasing EET
      levels in vivo could modulate an LPS-induced inflammatory response in the liver.
      However, LPS did have significant effects on plasma eicosanoid levels and hepatic
      Ephx2 expression, suggesting that in vivo EET levels are modulated in response to
      an inflammatory signal.

PMID- 18815354
TI  - Identification of two isoforms of the Kisspeptin-1 receptor (kiss1r) generated by
      alternative splicing in a modern teleost, the Senegalese sole (Solea
      senegalensis).
AB  - The KISSPEPTIN-1 receptor (KISS1R) and its ligands (KISSPEPTINS) are implicated
      in the regulation of the onset of puberty. We report the coding region and
      genomic structure of the kiss1r gene of a modern teleost, the Senegalese sole
      (Ss). Ss kiss1r cDNA contained an opening frame of 1137 bp, which results in a
      predicted 378 amino acid protein. Searching genomic databases allowed the
      identification of kiss1r orthologues in six new species belonging to three
      vertebrate groups and established the evolutionary relationships of all KISS1R
      sequences available to date. Analysis of Ss kiss1r revealed for the first time in
      any vertebrate KISS1R gene the presence of features that are characteristic of a
      mechanism of alternative splicing. This was confirmed by the identification of
      two transcripts, Ss kiss1r_v1 and Ss kiss1r_v2. The latter, arising from intron
      III retention, contained a 27 codons insert in transmembrane region 4 with two
      stop codons, suggesting it may lead to a truncated protein. The mRNA of the two
      variants was differently expressed in several tissues. In the brain, levels of
      the Ss kiss1r_v1 were higher than those of Ss kiss1r_v2. In the gonads, the
      opposite was observed. Both isoforms exhibited changes depending on sex and
      maturity stage. The presence of two variants may help to explain some
      discrepancies observed in past studies regarding KISS1R expression during
      puberty. Thus, the existence of alternative splicing for the KISS1R gene may
      contribute to our understanding of the many physiological functions suspected to
      be mediated by KISSPEPTIN-KISS1R signaling.

PMID- 18815355
TI  - Successful cryopreservation of mouse oocytes by using low concentrations of
      trehalose and dimethylsulfoxide.
AB  - Sugars such as trehalose, sucrose, and glucose are effectively used by a variety
      of animals (e.g., brine shrimp, tardigrades, some frogs, and insects), as well as
      by bacteria, yeasts, and plant seeds to survive freezing and extreme drying. The
      objective of this study was to examine the potential application of sugars to
      mammalian oocyte cryopreservation. To this end, we used trehalose, a nonreducing
      disaccharide, and mouse metaphase II oocytes as models. Our experiments show that
      extracellular trehalose alone affords some protection at high subzero
      temperatures (e.g., -15 degrees C), which diminishes with further cooling of the
      oocytes to -30 degrees C and below. When present both intracellularly and
      extracellularly, trehalose dramatically improves the cryosurvival with increasing
      extracellular concentrations to 0.5 M, even after cooling to -196 degrees C.
      Furthermore, the combination of intracellular and extracellular trehalose with
      small amounts of a conventional penetrating cryoprotectant (i.e., 0.5 M
      dimethylsulfoxide) provide high survival, fertilization, and embryonic
      development rates statistically similar to untreated controls. When transferred
      to foster mothers, cryopreserved oocytes give rise to healthy offspring showing
      the proof of principle. Our experiments with differential scanning calorimetry
      indicate that when cooled using the same cryopreservation protocol, the mixture
      of 0.5 M trehalose and cryopreservation medium undergoes glass transition at high
      subzero temperatures, which further substantiates the use of sugars as
      intracellular and extracellular cryoprotectants. Taken together, our results are
      in agreement with the survival schemes in nature and demonstrate the successful
      use of sugars in cryopreservation of mammalian oocytes.

PMID- 18815356
TI  - Steroidogenic enzyme and key decidualization marker dysregulation in endometrial
      stromal cells from women with versus without endometriosis.
AB  - Identification of mechanisms underlying endometriosis pathogenesis will
      facilitate understanding and treatment of infertility and pain associated with
      this disorder. Herein, we investigated the expression of steroidogenic pathway
      enzymes and key decidualization biomarkers in endometrial tissue and in eutopic
      endometrial stromal fibroblasts (hESFs) from women with vs. those without
      endometriosis, and subsequently treated in vitro with 8-bromo-cAMP (8-Br-cAMP) or
      progesterone (P4). Real-time quantitative PCR, immunohistochemistry, ELISA, and
      radiometric aromatase activity assay were used. The results demonstrate
      significantly increased (14.5-fold; P=0.037) expression of aromatase in eutopic
      endometrium of women with disease. In 8-Br-cAMP-treated hESF from eutopic
      endometrium of women with endometriosis, the balance in estradiol (E2) and P4
      biosynthetic and metabolizing enzymes is disturbed (decreased HSD3B1 and HSD17B2,
      and increased HSD17B1 and aromatase), with the equilibrium being shifted towards
      an E2-enriched milieu. However, hESF from the same group of women treated with P4
      did not demonstrate such responsiveness. Lower expression of IGFBP1 and prolactin
      mRNA and protein was observed in hESF from women with vs. those without
      endometriosis in response to 8-Br-cAMP, but not P4, suggesting a blunted response
      of these decidual biomarkers to activation of the PKA pathway in eutopic
      endometrium in women with disease. The dichotomy of 8-Br-cAMP regulation of
      select steroidogenic enzymes leading to an enriched E2 milieu within the
      endometrium and a blunted response of decidual biomarkers to this decidualizing
      agent of hESF from women with endometriosis suggests resistance to full
      decidualization of the stromal fibroblasts and mechanisms underlying implantation
      failure and the pathophysiology of this disorder.

PMID- 18815357
TI  - Expression and activity of Toll-like receptors 1-9 in the human term placenta and
      changes associated with labor at term.
AB  - Inflammatory processes are involved in the initiation and maintenance of labor,
      suggesting that Toll-like receptor (TLR) activity within gestation-associated
      tissues, such as the placenta, might contribute to the process of parturition.
      Expression of transcripts for TLR1-TLR10 was examined in term (>37 wk of
      gestation) human placentas collected in the absence of labor (elective caesarean
      sections; ECS; n = 11) and after the completion of labor (normal vaginal
      delivery; NVD; n = 12). Placental explants were cultured in the presence of
      agonists for TLR2, TLR3, TLR4, TLR5, TLR7, TLR8, and TLR9, and cytokine
      production after 24 h was examined. All placentas expressed transcripts for TLR1
      TLR10. Reactivity to all agonists except CpG oligonucleotides was observed,
      indicating that, other than TLR9, all of the receptors studied yielded functional
      responses. Placental explants prepared from NVD placentas (n = 17) produced
      significantly more TNFA in response to lipopolysaccharide (TLR4 agonist) and
      resiquimod (TLR7/8 agonist) than explants from ECS placentas (n = 17). In
      contrast, gene expression analysis revealed that only transcripts for TLR2 and
      TLR5 were significantly elevated in association with labor. The human term
      placenta expresses a variety of functional TLRs, indicating that this family of
      receptors has an important role in parturition via as yet undetermined cell types
      and signaling pathways.

PMID- 18815358
TI  - Hypoxia-inducible factor 1alpha (HIF1A) mediates distinct steps of rat
      trophoblast differentiation in gradient oxygen.
AB  - Defective differentiation of invasive, placental trophoblast cells has been
      associated with several pregnancy-related disorders. This study examines the
      molecular, functional, and morphological differentiation of lineage-specific,
      trophoblast giant cells under a gradient of oxygen concentrations. Low oxygen
      (3%) inhibited differentiation, but this inhibition was relieved in a stepwise
      fashion with increasing levels of oxygen. The oxygen-sensitive hypoxia-inducible
      factor 1alpha (HIF1A) is a major transcriptional regulator of the cellular
      response to low oxygen, and increased HIF1A protein levels and activity
      corresponded with the maintenance of the stem cell-like state and inhibition of
      trophoblast differentiation in low oxygen. Furthermore, constitutive expression
      of an oxygen-insensitive, active form of HIF1A protein mimicked the effects of
      low oxygen, inhibiting the differentiation of trophoblast giant cells. This study
      is the first to delineate the stepwise effects of oxygen on the activation of the
      trophoblast giant cell differentiation process and establishes a new paradigm
      from which to investigate trophoblast differentiation. In addition, this is the
      first reported study to demonstrate that constitutive HIF1A activity mediates
      oxygen's inhibition of differentiation. These results suggest that a
      dysregulation of HIF1A could contribute to impaired placental development.

PMID- 18815359
TI  - A role for sphingosine kinase 1 in dextran sulfate sodium-induced colitis.
AB  - The bioactive lipid sphingosine-1-phosphate (S1P) is emerging as an important
      mediator of immune and inflammatory responses. S1P formation is catalyzed by
      sphingosine kinase (SK), of which the SK1 isoenzyme is activated by tumor
      necrosis alpha (TNF-alpha). SK1 has been shown to be required for mediating TNF
      alpha inflammatory responses in cells, including induction of cyclooxygenase 2
      (COX-2). Because TNF-alpha and COX-2 are increased in patients with inflammatory
      bowel disease (IBD), we investigated the role of SK1 in a murine model of
      colitis. SK1(-/-) mice treated with dextran sulfate sodium (DSS) had
      significantly less blood loss, weight loss, colon shortening, colon histological
      damage, and splenomegaly than did wild-type (WT) mice. In addition, SK1(-/-) mice
      had no systemic inflammatory response. Moreover, WT but not SK1(-/-) mice treated
      with dextran sulfate sodium had significant increases in blood S1P levels, colon
      SK1 message and activity, and colon neutrophilic infiltrate. Unlike WT mice, SK1(
      /-) mice failed to show colonic COX-2 induction despite an exaggerated TNF-alpha
      response; thus implicating for the first time SK1 in TNF-alpha-mediated COX-2
      induction in vivo. Inhibition of SK1 may prove to be a valuable therapeutic
      target by inhibiting systemic and local inflammation in IBD.

PMID- 18815360
TI  - Functional analysis of monocyte MHC class II compartments.
AB  - Circulating monocytes, as dendritic cell and macrophage precursors, exhibit
      several functions usually associated with antigen-presenting cells, such as
      phagocytosis and presence of endosomal/lysosomal degradative compartments
      particularly enriched in Lamp-1, MHC class II molecules, and other proteins
      related to antigen processing and MHC class II loading [MHC class II compartments
      (MIICs)]. Ultrastructural analysis of these organelles indicates that,
      differently from the multivesicular bodies present in dendritic cells, in
      monocytes the MIICs are characterized by a single perimetral membrane surrounding
      an electron-dense core. Analysis of their content reveals enrichment in
      myeloperoxidase, an enzyme classically associated with azurophilic granules in
      granulocytes and mast cell secretory lysosomes. Elevation in intracellular free
      calcium levels in monocytes induced secretion of beta-hexosaminidase, cathepsins,
      and myeloperoxidase in the extracellular milieu; surface up-regulation of MHC
      class II molecules; and appearance of lysosomal resident proteins. The Ca(2+)
      regulated surface transport mechanism of MHC class II molecules observed in
      monocytes is different from the tubulovesicular organization of the
      multivesicular bodies previously reported in dendritic cells and macrophages.
      Hence, in monocytes, MHC class II-enriched organelles combine degradative
      functions typical of lysosomes and regulated secretion typical of secretory
      lysosomes. More important, Ca(2+)-mediated up-regulation of surface MHC class II
      molecules is accompanied by extracellular release of lysosomal resident enzymes.

PMID- 18815361
TI  - Chemical targeting of the innate antiviral response by histone deacetylase
      inhibitors renders refractory cancers sensitive to viral oncolysis.
AB  - Intratumoral innate immunity can play a significant role in blocking the
      effective therapeutic spread of a number of oncolytic viruses (OVs). Histone
      deacetylase inhibitors (HDIs) are known to influence epigenetic modifications of
      chromatin and can blunt the cellular antiviral response. We reasoned that
      pretreatment of tumors with HDIs could enhance the replication and spread of OVs
      within malignancies. Here, we show that HDIs markedly enhance the spread of
      vesicular stomatitis virus (VSV) in a variety of cancer cells in vitro, in
      primary tumor tissue explants and in multiple animal models. This increased
      oncolytic activity correlated with a dampening of cellular IFN responses and
      augmentation of virus-induced apoptosis. These results illustrate the general
      utility of HDIs as chemical switches to regulate cellular innate antiviral
      responses and to provide controlled growth of therapeutic viruses within
      malignancies. HDIs could have a profoundly positive impact on the clinical
      implementation of OV therapeutics.

PMID- 18815362
TI  - cAMP/PKA signaling and RIM1alpha mediate presynaptic LTP in the lateral amygdala.
AB  - NMDA receptor-dependent long-term potentiation (LTP) of glutamatergic synaptic
      transmission in sensory pathways from auditory thalamus or cortex to the lateral
      amygdala (LA) underlies the acquisition of auditory fear conditioning. Whereas
      the mechanisms of postsynaptic LTP at thalamo-LA synapses are well understood,
      much less is known about the sequence of events mediating presynaptic NMDA
      receptor-dependent LTP at cortico-LA synapses. Here, we show that presynaptic
      cortico-LA LTP can be entirely accounted for by a persistent increase in the
      vesicular release probability. At the molecular level, we found that signaling
      via the cAMP/PKA pathway is necessary and sufficient for LTP induction. Moreover,
      by using mice lacking the active-zone protein and PKA target RIM1alpha
      (RIM1alpha(-/-)), we demonstrate that RIM1alpha is required for both chemically
      and synaptically induced presynaptic LTP. Further analysis of cortico-LA synaptic
      transmission in RIM1alpha(-/-) mice revealed a deficit in Ca(2+)-release coupling
      leading to a lower baseline release probability. Our results reveal the molecular
      mechanisms underlying the induction of presynaptic LTP at cortico-LA synapses and
      indicate that RIM1alpha-dependent LTP may involve changes in Ca(2+)-release
      coupling.

PMID- 18815364
TI  - Opening the climate envelope reveals no macroscale associations with climate in
      European birds.
AB  - Predicting how species distributions might shift as global climate changes is
      fundamental to the successful adaptation of conservation policy. An increasing
      number of studies have responded to this challenge by using climate envelopes,
      modeling the association between climate variables and species distributions.
      However, it is difficult to quantify how well species actually match climate.
      Here, we use null models to show that species-climate associations found by
      climate envelope methods are no better than chance for 68 of 100 European bird
      species. In line with predictions, we demonstrate that the species with
      distribution limits determined by climate have more northerly ranges. We conclude
      that scientific studies and climate change adaptation policies based on the
      indiscriminate use of climate envelope methods irrespective of species
      sensitivity to climate may be misleading and in need of revision.

PMID- 18815363
TI  - Control of feeding behavior in C. elegans by human G protein-coupled receptors
      permits screening for agonist-expressing bacteria.
AB  - G protein-coupled receptors (GPCRs) have a key role in many biological processes
      and are important drug targets for many human diseases. Therefore, understanding
      the molecular interactions between GPCRs and their ligands would improve drug
      design. Here, we describe an approach that allows the rapid identification of
      functional agonists expressed in bacteria. Transgenic Caenorhabditis elegans
      expressing the human chemokine receptor 5 (CCR5) in nociceptive neurons show
      avoidance behavior on encounter with the ligand MIP-1alpha and avoid feeding on
      Escherichia coli expressing MIP-1alpha compared with control bacteria. This
      system allows a simple activity screen, based on the distribution of transgenic
      worms in a binary food-choice assay, without a requirement for protein
      purification or tagging. By using this approach, a library of 68 MIP-1alpha
      variants was screened, and 13 critical agonist residues involved in CCR5
      activation were identified, four of which (T8, A9, N22, and A25) have not been
      described previously, to our knowledge. Identified residues were subsequently
      validated in receptor binding assays and by calcium flux assays in mammalian
      cells. This approach serves not only for structure/function studies as
      demonstrated, but may be used to facilitate the discovery of agonists within
      bacterial libraries.

PMID- 18815365
TI  - Higher criticism thresholding: Optimal feature selection when useful features are
      rare and weak.
AB  - In important application fields today-genomics and proteomics are examples
      selecting a small subset of useful features is crucial for success of Linear
      Classification Analysis. We study feature selection by thresholding of feature Z
      scores and introduce a principle of threshold selection, based on the notion of
      higher criticism (HC). For i = 1, 2, ..., p, let pi(i) denote the two-sided P
      value associated with the ith feature Z-score and pi((i)) denote the ith order
      statistic of the collection of P-values. The HC threshold is the absolute Z-score
      corresponding to the P-value maximizing the HC objective (i/p -
      pi((i)))/sqrt{i/p(1-i/p)}. We consider a rare/weak (RW) feature model, where the
      fraction of useful features is small and the useful features are each too weak to
      be of much use on their own. HC thresholding (HCT) has interesting behavior in
      this setting, with an intimate link between maximizing the HC objective and
      minimizing the error rate of the designed classifier, and very different behavior
      from popular threshold selection procedures such as false discovery rate
      thresholding (FDRT). In the most challenging RW settings, HCT uses an
      unconventionally low threshold; this keeps the missed-feature detection rate
      under better control than FDRT and yields a classifier with improved
      misclassification performance. Replacing cross-validated threshold selection in
      the popular Shrunken Centroid classifier with the computationally less expensive
      and simpler HCT reduces the variance of the selected threshold and the error rate
      of the constructed classifier. Results on standard real datasets and in
      asymptotic theory confirm the advantages of HCT.

PMID- 18815366
TI  - An insect symbiosis is influenced by bacterium-specific polymorphisms in outer
      membrane protein A.
AB  - Beneficial bacterial symbioses are ubiquitous in nature. However, the functional
      and molecular basis of host tolerance to resident symbiotic microbes, in contrast
      to resistance to closely related bacteria that are recognized as foreign, remain
      largely unknown. We used the tsetse fly (Glossina morsitans), which depends on
      symbiotic flora for fecundity and has limited exposure to foreign microbes, to
      investigate the tolerance phenomenon exhibited during symbiosis. We examined the
      potential role of bacterium-specific polymorphisms present in the major bacterial
      surface protein, outer-membrane protein A (OmpA), on host infection outcomes.
      Tsetse were successfully superinfected with their mutualistic facultative
      symbiont, Sodalis glossinidius, whereas infections with Escherichia coli K12 were
      lethal. In contrast, tsetse were resistant to an E. coli OmpA mutant strain,
      whereas recombinant Sodalis expressing E. coli OmpA became pathogenic. Profiling
      of tsetse immunity-related gene expression incriminated peptidoglycan recognition
      protein (pgrp)-lb as a determinant of the infection outcomes we observed. RNAi
      induced knockdown of tsetse pgrp-lb significantly reduced host mortality after
      infection with otherwise lethal E. coli K12. Our results show that polymorphisms
      in the exposed loop domains of OmpA represent a microbial adaptation that
      mediates host tolerance of endogenous symbiotic bacteria.

PMID- 18815368
TI  - Drug interactions modulate the potential for evolution of resistance.
AB  - Antimicrobial treatments increasingly rely on multidrug combinations, in part
      because of the emergence and spread of antibiotic resistance. The continued
      effectiveness of combination treatments depends crucially on the frequency with
      which multidrug resistance arises. Yet, it is unknown how this propensity for
      resistance depends on cross-resistance and on epistatic interactions-ranging from
      synergy to antagonism-between the drugs. Here, we analyzed how interactions
      between pairs of drugs affect the spontaneous emergence of resistance in the
      medically important pathogen Staphylococcus aureus. Resistance is selected for
      within a window of drug concentrations high enough to inhibit wild-type growth
      but low enough for some resistant mutants to grow. Introducing an experimental
      method for high-throughput colony imaging, we counted resistant colonies arising
      across a two-dimensional matrix of drug concentrations for each of three drug
      pairs. Our data show that these different drug combinations have significantly
      different impacts on the size of the window of drug concentrations where
      resistance is selected for. We framed these results in a mathematical model in
      which the frequencies of resistance to single drugs, cross-resistance, and
      epistasis combine to determine the propensity for multidrug resistance. The
      theory suggests that drug pairs which interact synergistically, preferred for
      their immediate efficacy, may in fact favor the future evolution of resistance.
      This framework reveals the central role of drug epistasis in the evolution of
      resistance and points to new strategies for combating the emergence of drug
      resistant bacteria.

PMID- 18815367
TI  - Distinct size distribution of endogeneous siRNAs in maize: Evidence from deep
      sequencing in the mop1-1 mutant.
AB  - Small RNAs from plants are known to be highly complex and abundant, with this
      complexity proportional to genome size. Most endogenous siRNAs in Arabidopsis are
      dependent on RNA-DEPENDENT RNA POLYMERASE 2 (RDR2) for their biogenesis. Recent
      work has demonstrated that the maize MEDIATOR OF PARAMUTATION1 (mop1) gene is a
      predicted ortholog of RDR2. The mop1 gene is required for establishment of
      paramutation and maintenance of transcriptional silencing of transposons and
      transgenes, suggesting the potential involvement of small RNAs. We analyzed small
      RNAs in wild-type maize and in the isogenic mop1-1 loss-of-function mutant by
      using Illumina's sequencing-by-synthesis (SBS) technology, which allowed us to
      characterize the complement of maize small RNAs to considerable depth. Similar to
      rdr2 in Arabidopsis, in mop1-1, the 24-nucleotide (nt) endogenous heterochromatic
      short-interfering siRNAs were dramatically reduced, resulting in an enrichment of
      miRNAs and transacting siRNAs. In contrast to the Arabidopsis rdr2 mutant, the
      mop1-1 plants retained a highly abundant heterochromatic approximately 22-nt
      class of small RNAs, suggesting a second mechanism for heterochromatic siRNA
      production. The enrichment of miRNAs and loss of 24-nt heterochromatic siRNAs in
      mop1-1 should be advantageous for miRNA discovery as the maize genome becomes
      more fully sequenced.

PMID- 18815369
TI  - Salmonella pathogenesis reveals that BMP signaling regulates blood cell
      homeostasis and immune responses in Drosophila.
AB  - Intercellular signaling by bone morphogenetic proteins (BMPs) regulates
      developmental decisions in virtually all animals. Here, we report that
      Decapentaplegic (Dpp; a Drosophila BMP family member) plays a role in blood cell
      homeostasis and immune responses by regulating a transcription factor cascade.
      The cascade begins with Dpp repression of Zfh1, continues with Zfh1 activation of
      Serpent (Srp; a GATA factor), and terminates with Srp activation of U-shaped
      (Ush) in hematopoietic cells. Hyperactivation of Zfh1, Srp, and Ush in dpp
      mutants leads to hyperplasia of plasmatocytes. Salmonella challenge revealed that
      in dpp mutants the misregulation of this cascade also prevents the generation of
      lamellocytes. These findings support the hypothesis that Ush participates in a
      switch between plasmatocyte and lamellocyte fate in a common precursor and
      further suggests a mechanism for how all blood cell types can arise from a single
      progenitor. These results also demonstrate that combining Drosophila and
      Salmonella genetics can provide novel opportunities for advancing our knowledge
      of hematopoiesis and innate immunity.

PMID- 18815370
TI  - RNAi screening for kinases and phosphatases identifies FoxO regulators.
AB  - Forkhead box class O (FoxO) transcription factors are key regulators of growth,
      metabolism, life span, and stress resistance. FoxOs integrate signals from
      different pathways and guide the cellular response to varying energy and stress
      conditions. FoxOs are modulated by several signaling pathways, e.g., the insulin
      TOR signaling pathway and the stress induced JNK signaling pathway. Here, we
      report a genome wide RNAi screen of kinases and phosphatases aiming to find
      regulators of dFoxO activity in Drosophila S2 cells. By using a combination of
      transcriptional activity and localization assays we identified several enzymes
      that modulate dFoxO transcriptional activity, intracellular localization and/or
      protein stability. Importantly, several currently known dFoxO regulators were
      found in the screening, confirming the validity of our approach. In addition,
      several interesting new regulators were identified, including protein kinase C
      and glycogen synthase kinase 3beta, two proteins with important roles in insulin
      signaling. Furthermore, several mammalian orthologs of the proteins identified in
      Drosophila also regulate FOXO activity in mammalian cells. Our results contribute
      to a comprehensive understanding of FoxO regulatory processes.

PMID- 18815371
TI  - Estrogens directly potentiate neuronal L-type Ca2+ channels.
AB  - L-type voltage-gated Ca(2+)channels (VGCC) play an important role in dendritic
      development, neuronal survival, and synaptic plasticity. Recent studies have
      demonstrated that the gonadal steroid estrogen rapidly induces Ca(2+) influx in
      hippocampal neurons, which is required for neuroprotection and potentiation of
      LTP. The mechanism by which estrogen rapidly induces this Ca(2+) influx is not
      clearly understood. We show by electrophysiological studies that extremely low
      concentrations of estrogens acutely potentiate VGCC in hippocampal neurons,
      hippocampal slices, and HEK-293 cells transfected with neuronal L-type VGCC, in a
      manner that was estrogen receptor (ER)-independent. Equilibrium, competitive, and
      whole-cell binding assays indicate that estrogen directly interacts with the
      VGCC. Furthermore, a L-type VGCC antagonist to the dihydropyridine site displaced
      estrogen binding to neuronal membranes, and the effects of estrogen were markedly
      attenuated in a mutant, dihydropyridine-insensitive L-type VGCC, demonstrating a
      direct interaction of estrogens with L-type VGCC. Thus, estrogen-induced
      potentiation of calcium influx via L-type VGCC may link electrical events with
      rapid intracellular signaling seen with estrogen exposure leading to modulation
      of synaptic plasticity, neuroprotection, and memory formation.

PMID- 18815372
TI  - Analysis and synthesis of high-amplitude Cis-elements in the mammalian circadian
      clock.
AB  - Mammalian circadian clocks consist of regulatory loops mediated by Clock/Bmal1
      binding elements, DBP/E4BP4 binding elements, and RevErbA/ROR binding elements.
      As a step toward system-level understanding of the dynamic transcriptional
      regulation of the oscillator, we constructed and used a mammalian
      promoter/enhancer database (http://promoter.cdb.riken.jp/) with computational
      models of the Clock/Bmal1-binding elements, DBP/E4BP4 binding elements, and
      RevErbA/ROR binding elements to predict new targets of the clock and subsequently
      validated these targets at the level of the cell and organism. We further
      demonstrated the predictive nature of these models by generating and testing
      synthetic regulatory elements that do not occur in nature and showed that these
      elements produced high-amplitude circadian gene regulation. Biochemical
      experiments to characterize these synthetic elements revealed the importance of
      the affinity balance between transactivators and transrepressors in generating
      high-amplitude circadian transcriptional output. These results highlight the
      power of comparative genomics approaches for system-level identification and
      knowledge-based design of dynamic regulatory circuits.

PMID- 18815373
TI  - Spontaneous neural activity during human slow wave sleep.
AB  - Slow wave sleep (SWS) is associated with spontaneous brain oscillations that are
      thought to participate in sleep homeostasis and to support the processing of
      information related to the experiences of the previous awake period. At the
      cellular level, during SWS, a slow oscillation (<1 Hz) synchronizes firing
      patterns in large neuronal populations and is reflected on electroencephalography
      (EEG) recordings as large-amplitude, low-frequency waves. By using simultaneous
      EEG and event-related functional magnetic resonance imaging (fMRI), we
      characterized the transient changes in brain activity consistently associated
      with slow waves (>140 microV) and delta waves (75-140 microV) during SWS in 14
      non-sleep-deprived normal human volunteers. Significant increases in activity
      were associated with these waves in several cortical areas, including the
      inferior frontal, medial prefrontal, precuneus, and posterior cingulate areas.
      Compared with baseline activity, slow waves are associated with significant
      activity in the parahippocampal gyrus, cerebellum, and brainstem, whereas delta
      waves are related to frontal responses. No decrease in activity was observed.
      This study demonstrates that SWS is not a state of brain quiescence, but rather
      is an active state during which brain activity is consistently synchronized to
      the slow oscillation in specific cerebral regions. The partial overlap between
      the response pattern related to SWS waves and the waking default mode network is
      consistent with the fascinating hypothesis that brain responses synchronized by
      the slow oscillation restore microwake-like activity patterns that facilitate
      neuronal interactions.

PMID- 18815374
TI  - Fabrication of ZnPc/protein nanohorns for double photodynamic and hyperthermic
      cancer phototherapy.
AB  - Multifunctionalization of carbon nanotubules is easily achieved by attaching
      functional molecules that provide specific advantages for microscopic
      applications. We fabricated a double photodynamic therapy (PDT) and
      photohyperthermia (PHT) cancer phototherapy system that uses a single laser. Zinc
      phthalocyanine (ZnPc) was loaded onto single-wall carbon nanohorns with holes
      opened (SWNHox), and the protein bovine serum albumin (BSA) was attached to the
      carboxyl groups of SWNHox. In this system, ZnPc was the PDT agent, SWNHox was the
      PHT agent, and BSA enhanced biocompatibility. The double phototherapy effect was
      confirmed in vitro and in vivo. When ZnPc-SWNHox-BSA was injected into tumors
      that were subcutaneously transplanted into mice, the tumors almost disappeared
      upon 670-nm laser irradiation. In contrast, the tumors continued to grow when
      only ZnPc or SWNHox-BSA was injected. We conclude that carbon nanotubules may be
      a valuable new tool for use in cancer phototherapy.

PMID- 18815375
TI  - In vivo enzymatic modulation of IgG glycosylation inhibits autoimmune disease in
      an IgG subclass-dependent manner.
AB  - IgG antibodies are potent inducers of proinflammatory responses. During
      autoimmune diseases such as arthritis and systemic lupus erythematosus, IgG
      autoantibodies are responsible for the chronic inflammation and destruction of
      healthy tissues by cross-linking Fc receptors on innate immune effector cells.
      The sugar moiety attached to the asparagine-297 residue in the constant domain of
      the antibody is critical for the overall structure and function of the molecule.
      Removal of this sugar domain leads to the loss of the proinflammatory activity,
      suggesting that in vivo modulation of antibody glycosylation might be a strategy
      to interfere with autoimmune processes. In this work, we investigated whether
      removal of the majority of the IgG-associated sugar domain by endoglycosidase S
      (EndoS) from Streptococcus pyogenes is able to interfere with autoimmune
      inflammation. We demonstrate that EndoS injection efficiently removes the IgG
      associated sugar domain in vivo and interferes with autoantibody-mediated
      proinflammatory processes in a variety of autoimmune models. Importantly,
      however, we observed a differential impact of EndoS-mediated sugar side chain
      hydrolysis on IgG activity depending on the individual IgG subclass.

PMID- 18815376
TI  - Computational prediction of RNA structural motifs involved in posttranscriptional
      regulatory processes.
AB  - Messenger RNA molecules are tightly regulated, mostly through interactions with
      proteins and other RNAs, but the mechanisms that confer the specificity of such
      interactions are poorly understood. It is clear, however, that this specificity
      is determined by both the nucleotide sequence and secondary structure of the
      mRNA. Here, we develop RNApromo, an efficient computational tool for identifying
      structural elements within mRNAs that are involved in specifying
      posttranscriptional regulations. By analyzing experimental data on mRNA decay
      rates, we identify common structural elements in fast-decaying and slow-decaying
      mRNAs and link them with binding preferences of several RNA binding proteins. We
      also predict structural elements in sets of mRNAs with common subcellular
      localization in mouse neurons and fly embryos. Finally, by analyzing pre-microRNA
      stem-loops, we identify structural differences between pre-microRNAs of animals
      and plants, which provide insights into the mechanism of microRNA biogenesis.
      Together, our results reveal unexplored layers of posttranscriptional regulations
      in groups of RNAs and are therefore an important step toward a better
      understanding of the regulatory information conveyed within RNA molecules. Our
      new RNA motif discovery tool is available online.

PMID- 18815377
TI  - Experimental characterization of shear transformation zones for plastic flow of
      bulk metallic glasses.
AB  - We report experimental characterization of shear transformation zones (STZs) for
      plastic flow of bulk metallic glasses (BMGs) based on a newly developed
      cooperative shearing model [Johnson WL, Samwer K (2005) A universal criterion for
      plastic yielding of metallic glasses with a (T/T(g))(2/3) temperature dependence.
      Phys Rev Lett 95: 195501]. The good agreement between experimental measurements
      and theoretical predictions in the STZ volumes provides compelling evidence that
      the plastic flow of metallic glasses occurs through cooperative shearing of
      unstable STZs activated by shear stresses. Moreover, the ductility of BMGs was
      found to intrinsically correlate with their STZ volumes. The experiments
      presented herein pave a way to gain a quantitative insight into the atomic-scale
      mechanisms of BMG mechanical behavior.

PMID- 18815378
TI  - Opposing functions of IKKbeta during acute and chronic intestinal inflammation.
AB  - NF-kappaB is a key transcriptional regulator of inflammatory responses, but also
      controls expression of prosurvival genes, whose products protect tissues from
      damage and may thus act indirectly in an antiinflammatory fashion. The variable
      importance of these two distinct NF-kappaB-controlled responses impacts the
      potential utility of NF-kappaB inhibition as a treatment strategy for intractable
      inflammatory conditions, such as inflammatory bowel disease. Here, we show in
      murine models that inhibition of IKKbeta-dependent NF-kappaB activation
      exacerbates acute inflammation, but attenuates chronic inflammatory disease in
      the intestinal tract. Acute ulcerating inflammation is aggravated because of
      diminished NF-kappaB-mediated protection against epithelial cell apoptosis and
      delayed mucosal regeneration secondary to reduced NF-kappaB-dependent recruitment
      of inflammatory cells that secrete cytoprotective factors. In contrast, in IL-10
      deficient mice, which serve as a model of chronic T cell-dependent colitis,
      ablation of IKKbeta in the intestinal epithelium has no impact, yet IKKbeta
      deficiency in myeloid cells attenuates inflammation and prolongs survival. These
      results highlight the striking context and tissue dependence of the
      proinflammatory and antiapoptotic functions of NF-kappaB. Our findings caution
      against the therapeutic use of IKKbeta/NF-kappaB inhibitors in acute inflammatory
      settings dominated by cell loss and ulceration.

PMID- 18815379
TI  - Role of selection in the emergence of lineages and the evolution of virulence in
      Neisseria meningitidis.
AB  - Neisseria meningitis is a human commensal bacterium that occasionally causes life
      threatening disease. As with a number of other bacterial pathogens, meningococcal
      populations comprise distinct lineages, which persist over many decades and
      during global spread in the face of high rates of recombination. In addition, the
      propensity to cause invasive disease is associated with particular
      "hyperinvasive" lineages that coexist with less invasive lineages despite the
      fact that disease does not contribute to host-to-host transmission. Here, by
      combining a modeling approach with molecular epidemiological data from 1,108
      meningococci isolated in the Czech Republic over 27 years, we show that
      interstrain competition, mediated by immune selection, can explain both the
      persistence of multiple discrete meningococcal lineages and the association of a
      subset of these with invasive disease. The model indicates that the combinations
      of allelic variants of housekeeping genes that define these lineages are
      associated with very small differences in transmission efficiency among hosts.
      These findings have general implications for the emergence of lineage structure
      and virulence in recombining bacterial populations.

PMID- 18815380
TI  - Preneoplastic lesion growth driven by the death of adjacent normal stem cells.
AB  - Clonal expansion of premalignant lesions is an important step in the progression
      to cancer. This process is commonly considered to be a consequence of sustaining
      a proliferative mutation. Here, we investigate whether the growth trajectory of
      clones can be better described by a model in which clone growth does not depend
      on a proliferative advantage. We developed a simple computer model of clonal
      expansion in an epithelium in which mutant clones can only colonize space left
      unoccupied by the death of adjacent normal stem cells. In this model, competition
      for space occurs along the frontier between mutant and normal territories, and
      both the shapes and the growth rates of lesions are governed by the differences
      between mutant and normal cells' replication or apoptosis rates. The behavior of
      this model of clonal expansion along a mutant clone's frontier, when apoptosis of
      both normal and mutant cells is included, matches the growth of UVB-induced p53
      mutant clones in mouse dorsal epidermis better than a standard exponential growth
      model that does not include tissue architecture. The model predicts precancer
      cell mutation and death rates that agree with biological observations. These
      results support the hypothesis that clonal expansion of premalignant lesions can
      be driven by agents, such as ionizing or nonionizing radiation, that cause cell
      killing but do not directly stimulate cell replication.

PMID- 18815381
TI  - Endosymbiont gene functions impaired and rescued by polymerase infidelity at
      poly(A) tracts.
AB  - Among host-dependent bacteria that have evolved by extreme reductive genome
      evolution, long-term bacterial endosymbionts of insects have the smallest (160
      790 kb) and most A + T-rich (>70%) bacterial genomes known to date. These genomes
      are riddled with poly(A) tracts, and 5-50% of genes contain tracts of 10 As or
      more. Here, we demonstrate transcriptional slippage at poly(A) tracts within
      genes of Buchnera aphidicola associated with aphids and Blochmannia
      pennsylvanicus associated with ants. Several tracts contain single frameshift
      deletions; these apparent pseudogenes showed patterns of constraint consistent
      with purifying selection on the encoded proteins. Transcriptional slippage
      yielded a heterogeneous population of transcripts with variable numbers of As in
      the tract. Across several frameshifted genes, including B. aphidicola cell wall
      biosynthesis genes and a B. pennsylvanicus histidine biosynthesis gene, 12-50% of
      transcripts contained corrected reading frames that could potentially yield full
      length proteins. In situ immunostaining confirmed the production of the cell wall
      biosynthetic enzyme UDP-N-acetylmuramyl pentapeptide synthase encoded by the
      frameshifted murF gene. Simulation studies indicated an overrepresentation of
      poly(A) tracts in endosymbiont genomes relative to other A + T-rich bacterial
      genomes. Polymerase infidelity at poly(A) tracts rescues the functionality of
      genes with frameshift mutations and, conversely, reduces the efficiency of
      expression for in-frame genes carrying poly(A) regions. These features of
      homopolymeric tracts could be exploited to manipulate gene expression in small
      synthetic genomes.

PMID- 18815382
TI  - Further evidence for the mandatory nature of polysaccharide debranching for the
      aggregation of semicrystalline starch and for overlapping functions of
      debranching enzymes in Arabidopsis leaves.
AB  - Four isoforms of debranching enzymes are found in the genome of Arabidopsis
      (Arabidopsis thaliana): three isoamylases (ISA1, ISA2, and ISA3) and a
      pullulanase (PU1). Each isoform has a specific function in the starch pathway:
      synthesis and/or degradation. In this work we have determined the levels of
      functional redundancy existing between these isoforms by producing and analyzing
      different combinations of mutations: isa3-1 pu1-1, isa1-1 isa3-1, and isa1-1 isa3
      1 pu1-1. While the starch content strongly increased in the isa3-1 pu1-1 double
      mutant, the latter decreased by over 98% in the isa1-1 isa3-1 genotype and almost
      vanished in triple mutant combination. In addition, whereas the isa3-1 pu1-1
      double mutant synthesizes starch very similar to that of the wild type, the
      structure of the residual starch present either in isa1-1 isa3-1 or in isa1-1
      isa3-1 pu1-1 combination is deeply affected. In the same way, water-soluble
      polysaccharides that accumulate in the isa1-1 isa3-1 and isa1-1 isa3-1 pu1-1
      genotypes display strongly modified structure compared to those found in isa1-1.
      Taken together, these results show that in addition to its established function
      in polysaccharide degradation, the activity of ISA3 is partially redundant to
      that of ISA1 for starch synthesis. Our results also reveal the dual function of
      pullulanase since it is partially redundant to ISA3 for degradation and to ISA1
      for synthesis. Finally, x-ray diffraction analyses suggest that the crystallinity
      and the presence of the 9- to 10-nm repetition pattern in starch precisely depend
      on the level of debranching enzyme activity.

PMID- 18815383
TI  - Molecular characterization of organelle-type Nudix hydrolases in Arabidopsis.
AB  - Nudix (for nucleoside diphosphates linked to some moiety X) hydrolases act to
      hydrolyze ribonucleoside and deoxyribonucleoside triphosphates, nucleotide
      sugars, coenzymes, or dinucleoside polyphosphates. Arabidopsis (Arabidopsis
      thaliana) contains 27 genes encoding Nudix hydrolase homologues (AtNUDX1 to -27)
      with a predicted distribution in the cytosol, mitochondria, and chloroplasts.
      Previously, cytosolic Nudix hydrolases (AtNUDX1 to -11 and -25) were
      characterized. Here, we conducted a characterization of organelle-type AtNUDX
      proteins (AtNUDX12 to -24, -26, and -27). AtNUDX14 showed pyrophosphohydrolase
      activity toward both ADP-ribose and ADP-glucose, although its K(m) value was
      approximately 100-fold lower for ADP-ribose (13.0+/-0.7 microm) than for ADP
      glucose (1,235+/-65 microm). AtNUDX15 hydrolyzed not only reduced coenzyme A
      (118.7+/-3.4 microm) but also a wide range of its derivatives. AtNUDX19 showed
      pyrophosphohydrolase activity toward both NADH (335.3+/-5.4 microm) and NADPH
      (36.9+/-3.5 microm). AtNUDX23 had flavin adenine dinucleotide
      pyrophosphohydrolase activity (9.1+/-0.9 microm). Both AtNUDX26 and AtNUDX27
      hydrolyzed diadenosine polyphosphates (n=4-5). A confocal microscopic analysis
      using a green fluorescent protein fusion protein showed that AtNUDX15 is
      distributed in mitochondria and AtNUDX14 -19, -23, -26, and -27 are distributed
      in chloroplasts. These AtNUDX mRNAs were detected ubiquitously in various
      Arabidopsis tissues. The T-DNA insertion mutants of AtNUDX13, -14, -15, -19, -20,
      -21, -25, -26, and -27 did not exhibit any phenotypical differences under normal
      growth conditions. These results suggest that Nudix hydrolases in Arabidopsis
      control a variety of metabolites and are pertinent to a wide range of
      physiological processes.

PMID- 18815384
TI  - Powdery mildew resistance conferred by loss of the ENHANCED DISEASE RESISTANCE1
      protein kinase is suppressed by a missense mutation in KEEP ON GOING, a regulator
      of abscisic acid signaling.
AB  - Loss-of-function mutations in the Arabidopsis (Arabidopsis thaliana) ENHANCED
      DISEASE RESISTANCE1 (EDR1) gene confer enhanced resistance to infection by
      powdery mildew (Golovinomyces cichoracearum). EDR1 encodes a protein kinase, but
      its substrates and the pathways regulated by EDR1 are unknown. To identify
      components of the EDR1 signal transduction pathway(s), we conducted a forward
      genetic screen for mutations that suppressed edr1-mediated disease resistance.
      Genetic mapping and cloning of one of these suppressor mutations revealed a
      recessive missense mutation in the KEEP ON GOING gene (KEG; At5g13530), which we
      designated keg-4. KEG encodes a multidomain protein that includes a RING E3
      ligase domain, a kinase domain, ankyrin repeats, and HERC2-like repeats. The KEG
      protein has previously been shown to have ubiquitin ligase activity and to
      negatively regulate protein levels of the transcription factor ABCISIC ACID
      INSENSITIVE5. KEG mRNA levels were found to be 3-fold higher in edr1 mutant
      plants compared to wild type. Loss-of-function mutations in KEG are seedling
      lethal and are hypersensitive to glucose and abscisic acid (ABA). The keg-4
      mutation, in contrast, conferred resistance to 6% glucose and suppressed edr1
      mediated hypersensitivity to ABA, suggesting that the keg-4 mutation suppresses
      ABA signaling by altering KEG function. Several ABA-responsive genes were found
      to be further up-regulated in the edr1 mutant following ABA treatment, and this
      up-regulation was suppressed by the keg-4 mutation. We conclude that edr1
      mediated resistance to powdery mildew is mediated, in part, by enhanced ABA
      signaling.

PMID- 18815385
TI  - Immunotherapy-responsive seizure-like episodes with potassium channel antibodies.

PMID- 18815386
TI  - Atrial fibrillation detected by mobile cardiac outpatient telemetry in
      cryptogenic TIA or stroke.
AB  - OBJECTIVE: Atrial fibrillation (AF) may be present within a subset of patients
      with presumed cryptogenic TIA or stroke and remains undetected by standard
      diagnostic methods. We hypothesized that AF may be an under-recognized mechanism
      for cryptogenic TIA/stroke. METHODS: A consecutive series of 56 patients with
      cryptogenic TIA/stroke was analyzed after diagnostic evaluation and Mobile
      Cardiac Outpatient Telemetry (MCOT) for up to 21 days. Demographic, radiographic,
      echocardiographic, and MCOT results were reviewed. Predictors of AF detection by
      MCOT were determined by univariate analysis including Student t test and Fisher
      exact tests and multivariate analysis. RESULTS: The median MCOT monitoring
      duration was 21 (range 5-21) days resulting in an AF detection rate of 23%
      (13/56). AF was first detected after a median of 7 (range 2-19) days of
      monitoring. Twenty-seven asymptomatic AF episodes were detected in the 13
      patients, of which 85% (23/27) were <30 seconds and the remaining 15% (4/27) were
      4-24 hours in duration. Diabetes was predictive of AF detection by both
      univariate (p = 0.024) and multivariate analysis (OR 6.15; 95% CI 1.16 to 32.73;
      p = 0.033). CONCLUSIONS: There is a high rate of atrial fibrillation (AF)
      detection by Mobile Cardiac Outpatient Telemetry (21 days) in patients with
      cryptogenic TIA/stroke that may be related to extended monitoring duration,
      patient selection, and inclusion of all new onset AF episodes. Brief AF episodes
      (<30 seconds) may be biomarkers of more prolonged and clinically significant AF.

PMID- 18815387
TI  - Cognitive impairment and structural brain damage in benign multiple sclerosis.
AB  - OBJECTIVE: Although in benign multiple sclerosis (BMS) locomotor disability is
      absent or only minimal, subclinical cognitive impairment seems to occur in many
      cases. Diffusion tensor (DT) MRI enables us to quantify the extent of "actual"
      tissue damage, which goes undetected when using conventional MRI. Against this
      background, we investigated the extent of structural brain damage underlying
      cognitive dysfunction in BMS, with the ultimate aim to move a first step toward a
      more reliable definition of this disease phenotype. METHODS: Conventional and DT
      MRI scans of the brain were acquired from 62 BMS patients. Thirty-six secondary
      progressive multiple sclerosis (SPMS) patients and 19 healthy subjects served as
      controls. In BMS patients, neuropsychological tests exploring memory, attention,
      and frontal lobe functions were administered. Normalized brain volume (NBV), mean
      diffusivity (MD), and fractional anisotropy (FA) of the normal-appearing white
      matter (NAWM) and MD of the gray matter (GM) were computed. RESULTS: Twelve BMS
      patients (19%) fulfilled predefined criteria for cognitive impairment. BMS
      patients had abnormal MD and FA values from both NAWM and GM. Whereas BMS
      patients without cognitive impairment had lower T2 LV (p = 0.03), higher NBV (p =
      0.006), and lower average GM MD (p = 0.03) than SPMS patients, BMS patients with
      cognitive impairment did not significantly differ from SPMS patients for any MRI
      derived metric. CONCLUSIONS: In benign multiple sclerosis (BMS), cognitive
      dysfunction is associated with severe structural brain damage, which resembles
      that of patients with a much more disabling disease course. A reliable definition
      of BMS should, therefore, include the preservation of cognitive functioning as an
      additional requisite.

PMID- 18815388
TI  - Modern health care for all Americans.

PMID- 18815389
TI  - Access to quality and affordable health care for every American.

PMID- 18815390
TI  - Health care in the next administration.

PMID- 18815391
TI  - Primum non nocere--the McCain plan for health insecurity.

PMID- 18815392
TI  - Symptomatic relief, but no cure--the Obama health care reform.

PMID- 18815393
TI  - Images in clinical medicine. New-onset clubbing associated with lung cancer.

PMID- 18815394
TI  - Storm over statins--the controversy surrounding pharmacologic treatment of
      children.

PMID- 18815395
TI  - Campaign contributions, lobbying, and the U.S. health sector--an update.

PMID- 18815396
TI  - Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke.
AB  - BACKGROUND: Intravenous thrombolysis with alteplase is the only approved
      treatment for acute ischemic stroke, but its efficacy and safety when
      administered more than 3 hours after the onset of symptoms have not been
      established. We tested the efficacy and safety of alteplase administered between
      3 and 4.5 hours after the onset of a stroke. METHODS: After exclusion of patients
      with a brain hemorrhage or major infarction, as detected on a computed
      tomographic scan, we randomly assigned patients with acute ischemic stroke in a
      1:1 double-blind fashion to receive treatment with intravenous alteplase (0.9 mg
      per kilogram of body weight) or placebo. The primary end point was disability at
      90 days, dichotomized as a favorable outcome (a score of 0 or 1 on the modified
      Rankin scale, which has a range of 0 to 6, with 0 indicating no symptoms at all
      and 6 indicating death) or an unfavorable outcome (a score of 2 to 6 on the
      modified Rankin scale). The secondary end point was a global outcome analysis of
      four neurologic and disability scores combined. Safety end points included death,
      symptomatic intracranial hemorrhage, and other serious adverse events. RESULTS:
      We enrolled a total of 821 patients in the study and randomly assigned 418 to the
      alteplase group and 403 to the placebo group. The median time for the
      administration of alteplase was 3 hours 59 minutes. More patients had a favorable
      outcome with alteplase than with placebo (52.4% vs. 45.2%; odds ratio, 1.34; 95%
      confidence interval [CI], 1.02 to 1.76; P=0.04). In the global analysis, the
      outcome was also improved with alteplase as compared with placebo (odds ratio,
      1.28; 95% CI, 1.00 to 1.65; P<0.05). The incidence of intracranial hemorrhage was
      higher with alteplase than with placebo (for any intracranial hemorrhage, 27.0%
      vs. 17.6%; P=0.001; for symptomatic intracranial hemorrhage, 2.4% vs. 0.2%;
      P=0.008). Mortality did not differ significantly between the alteplase and
      placebo groups (7.7% and 8.4%, respectively; P=0.68). There was no significant
      difference in the rate of other serious adverse events. CONCLUSIONS: As compared
      with placebo, intravenous alteplase administered between 3 and 4.5 hours after
      the onset of symptoms significantly improved clinical outcomes in patients with
      acute ischemic stroke; alteplase was more frequently associated with symptomatic
      intracranial hemorrhage. (ClinicalTrials.gov number, NCT00153036.)

PMID- 18815397
TI  - Drug-eluting or bare-metal stents for acute myocardial infarction.
AB  - BACKGROUND: Studies comparing percutaneous coronary intervention (PCI) with drug
      eluting and bare-metal coronary stents in acute myocardial infarction have been
      limited in size and duration. METHODS: We identified all adults undergoing PCI
      with stenting for acute myocardial infarction between April 1, 2003, and
      September 30, 2004, at any acute care, nonfederal hospital in Massachusetts with
      the use of a state-mandated database of PCI procedures. We performed propensity
      score matching on three groups of patients: all patients with acute myocardial
      infarction, all those with acute myocardial infarction with ST-segment elevation,
      and all those with acute myocardial infarction without ST-segment elevation.
      Propensity-score analyses were based on clinical, procedural, hospital, and
      insurance information collected at the time of the index procedure. Differences
      in the risk of death between patients receiving drug-eluting stents and those
      receiving bare-metal stents were determined from vital-statistics records.
      RESULTS: A total of 7217 patients were treated for acute myocardial infarction
      (4016 with drug-eluting stents and 3201 with bare-metal stents). According to
      analysis of matched pairs, the 2-year, risk-adjusted mortality rates were lower
      for drug-eluting stents than for bare-metal stents among all patients with
      myocardial infarction (10.7% vs. 12.8%, P=0.02), among patients with myocardial
      infarction with ST-segment elevation (8.5% vs. 11.6%, P=0.008), and among
      patients with myocardial infarction without ST-segment elevation (12.8% vs.
      15.6%, P=0.04). The 2-year, risk-adjusted rates of recurrent myocardial
      infarction were reduced in patients with myocardial infarction without ST-segment
      elevation who were treated with drug-eluting stents, and repeat revascularization
      rates were significantly reduced with the use of drug-eluting stents as compared
      with bare-metal stents in all groups. CONCLUSIONS: In patients presenting with
      acute myocardial infarction, treatment with drug-eluting stents is associated
      with decreased 2-year mortality rates and a reduction in the need for repeat
      revascularization procedures as compared with treatment with bare-metal stents.

PMID- 18815398
TI  - Lung cancer.

PMID- 18815399
TI  - Images in clinical medicine. Periungual fibromas.

PMID- 18815400
TI  - Case records of the Massachusetts General Hospital. Case 30-2008. A 47-year-old
      woman with a mass in the breast and a solitary lesion in the spine.

PMID- 18815401
TI  - Thrombolytic therapy for acute stroke--not a moment to lose.

PMID- 18815402
TI  - Calcific aortic stenosis--time to look more closely at the valve.

PMID- 18815403
TI  - Cell therapies for muscular dystrophy.

PMID- 18815404
TI  - Polygenes, risk prediction, and targeted prevention of breast cancer.

PMID- 18815405
TI  - Graves' disease.

PMID- 18815406
TI  - Zoledronic acid infusion and orbital inflammatory disease.

PMID- 18815407
TI  - Retraction: Barlogie et al. Duration of survival in patients with myeloma treated
      with thalidomide. N Engl J Med 2008;359:210-2.

PMID- 18815408
TI  - Environmental interventions to prevent falls in community-dwelling older people:
      a meta-analysis of randomized trials.
AB  - Objective. This study seeks to determine the efficacy of environmental
      interventions in reducing falls in community-dwelling older people. Method. A
      systematic review and meta-analysis of randomized trials was performed. Results.
      Pooled analysis of six trials (N = 3,298) demonstrated a 21% reduction in falls
      risk (relative risk [RR] = 0.79; 0.65 to 0.97). Heterogeneity was attributable to
      the large treatment effect of one trial. Analysis of a subgroup of studies with
      participants at high risk of falls (four trials, n = 570) demonstrated a
      clinically significant 39% reduction of falls (RR = 0.61; 0.47 to 0.79), an
      absolute risk difference of 26% for a number needed to treat four people.
      Discussion. Home assessment interventions that are comprehensive, are well
      focused, and incorporate an environmental-fit perspective with adequate follow-up
      can be successful in reducing falls with significant effects. The highest effects
      are associated with interventions that are conducted with high-risk groups.

PMID- 18815409
TI  - Gender, social ties, and cancer screening among elderly persons.
AB  - Objective. This study examines the association of social ties and cancer
      screening. Method. Data from the Longitudinal Study on Aging II include 4,419
      respondents (70 to 85) who completed Wave 2. The dependent variable is receipt of
      screening within the past 2 years, measured at Wave 2. Social network variables
      include marital status, interaction with friends, relatives, and children, and
      church attendance. Results. Women were higher on most social tie measures, except
      marriage, and less likely to have mammography than men were to have prostate
      cancer screening. Also, the decline of screening with age was greater for women.
      For women, screening was related to contact with friends, relatives, and children
      but not marital status or church attendance. For men, screening was higher in the
      married and church attendees, but contact with friends, relatives, and children
      was not associated with screening. Discussion. Cancer screening interventions
      that use interpersonal communication channels should target distinct
      relationships for older women and men

PMID- 18815410
TI  - Social networks and health-related quality of life among Chinese older adults
      with vision impairment.
AB  - OBJECTIVE: This study examines the associations between social networks and
      vision-specific health-related quality of life (HRQOL) among Chinese older
      adults. METHOD: Urban older adults with visual problems (N = 167) were
      interviewed using a structured questionnaire to assess self-reported visual
      functioning, general health, social networks, and vision-specific HRQOL.
      Objective visual function was clinically measured by ophthalmologists in terms of
      distance visual acuity. RESULTS: Findings indicate that age-related vision loss
      is significantly associated with older adults' social networks. Multiple
      regression analyses show that social networks are mildly related to vision
      specific HRQOL even after controlling for other variables, and that friendship
      network was a significant predictor, independent of family network, of vision
      specific HRQOL. DISCUSSION: Previous studies have emphasized the importance of
      family network, whereas this study finds that friendship network correlates more
      strongly with HRQOL measures among Chinese visually impaired older adults. This
      suggests a need to expand intervention beyond the family system.

PMID- 18815411
TI  - Home accidents in the community-dwelling elderly in Izmir, Turkey: how do
      prevalence and risk factors differ between high and low socioeconomic districts?
AB  - OBJECTIVE: To determine and compare the prevalence of and risk factors for home
      accidents in the elderly in two different districts. METHOD: This cross-sectional
      study involves 497 older participants ages 65 and older. Sociodemographic
      characteristics of the elderly and characteristics of the houses in two different
      regions are evaluated. Data are analyzed by chi-square and t test. RESULTS: The
      prevalence of home accidents was 39.3% in the low socioeconomic region and 13.1%
      in the high socioeconomic region within the past 6 months (p = .000). The most
      common type of home accident was fall (61.8%), followed by cut or piercing
      (22.0%). Home accidents are associated with being female and increasing age in
      the higher socioeconomic region, whereas being female, being unmarried, and
      living in a squatter house are associated with home accidents in the low
      socioeconomic region. DISCUSSION: The prevalence of home accidents in the elderly
      population who live in low socioeconomic region was higher.

PMID- 18815413
TI  - Leisure activities and mortality: does gender matter?
AB  - OBJECTIVES: This study examines the association between participation in leisure
      activities and mortality risk among older men and women. METHODS: A
      representative sample of 1,246 men and women ages 65 to 95, interviewed in 1991
      1992, were followed for 12 years. Cox regressions analyzed mortality risk.
      RESULTS: Participating in only a few activities doubled mortality risk compared
      to those with the highest participation levels, even after controlling for age,
      education, walking ability, and other health indicators. Women had a dose
      response relationship between overall participation and survival. Strong
      associations with survival were found for engagement in organizational activities
      and study circles among women and hobby activities and gardening among men.
      DISCUSSION: Results suggest gender differences in the association between leisure
      activities and mortality. Women display a decreasing mortality risk for each
      additional activity. Social activities have the strongest effects on survival
      among women, whereas men seem to benefit from solitary activities.

PMID- 18815412
TI  - Does the presence of a dementia special care unit improve nursing home quality?
AB  - OBJECTIVE: This study quantifies the effect of a new dementia special care unit
      (D-SCU) on the provision of care to all residents in a nursing home (NH). METHOD:
      The authors use data from the On-line Survey Certification and Reporting system
      to identify free-standing NHs that first reported a D-SCU between 1996 and 2003
      (N = 1,519). Fixed-effects models estimate the effect of a new D-SCU on the
      prevalence of each outcome (physical restraints, feeding tubes, and psychotropic
      medications) while controlling for secular trends. RESULTS: For all NHs, the use
      of physical restraints declined, the use of antipsychotics increased, and other
      measures remained relatively constant. The introduction of a D-SCU was not
      associated with changes in trends for any measure. DISCUSSION: Differences in
      care processes between NHs with and without D-SCUs are the result of differences
      in their underlying approach to care, not the result of care practice diffusion
      from the D-SCU.

PMID- 18815414
TI  - Differential associations of social support and social connectedness with
      structural features of social networks and the health status of older adults.
AB  - OBJECTIVE: This study explores the extent to which the constructs of social
      support and social connectedness differ in terms of their associations with the
      structural characteristics of social networks and the health status of older
      adults. METHOD: Trained interviewers conducted 126 face-to-face interviews with
      community-dwelling older adults aged 65 to 85 years. RESULTS: Having frequent
      contact with network members was positively associated with social support.
      Network density and having network members living in close proximity were
      positively associated with perceived social connectedness. Furthermore, perceived
      social connectedness had a significant positive association with health status,
      whereas social support did not. DISCUSSION: Perceived social connectedness may be
      relatively more important to the health and well-being of older adults than the
      perceived availability of social support. Efforts to enhance older adults' social
      relationships can be focused on developing friends and companions, allowing them
      to feel socially engaged in society.

PMID- 18815415
TI  - Crystal structures of Mycobacterium tuberculosis S-adenosyl-L-homocysteine
      hydrolase in ternary complex with substrate and inhibitors.
AB  - S-adenosylhomocysteine hydrolase (SAHH) is a ubiquitous enzyme that plays a
      central role in methylation-based processes by maintaining the intracellular
      balance between S-adenosylhomocysteine (SAH) and S-adenosylmethionine. We report
      the first prokaryotic crystal structure of SAHH, from Mycobacterium tuberculosis
      (Mtb), in complex with adenosine (ADO) and nicotinamide adenine dinucleotide.
      Structures of complexes with three inhibitors are also reported: 3'-keto
      aristeromycin (ARI), 2-fluoroadenosine, and 3-deazaadenosine. The ARI complex is
      the first reported structure of SAHH complexed with this inhibitor, and confirms
      the oxidation of the 3' hydroxyl to a planar keto group, consistent with its
      prediction as a mechanism-based inhibitor. We demonstrate the in vivo enzyme
      inhibition activity of the three inhibitors and also show that 2-fluoradenosine
      has bactericidal activity. While most of the residues lining the ADO-binding
      pocket are identical between Mtb and human SAHH, less is known about the binding
      mode of the homocysteine (HCY) appendage of the full substrate. We report the 2.0
      A resolution structure of the complex of SAHH cocrystallized with SAH. The most
      striking change in the structure is that binding of HCY forces a rotation of
      His363 around the backbone to flip out of contact with the 5' hydroxyl of the ADO
      and opens access to a nearby channel that leads to the surface. This complex
      suggests that His363 acts as a switch that opens up to permit binding of
      substrate, then closes down after release of the cleaved HCY. Differences in the
      entrance to this access channel between human and Mtb SAHH are identified.

PMID- 18815416
TI  - Solution structure of the extraterminal domain of the bromodomain-containing
      protein BRD4.
AB  - BRD4, which is a member of the BET (bromodomains and extraterminal) protein
      family, interacts preferentially with acetylated chromatin and possesses multiple
      cellular functions in meiosis, embryonic development, the cell cycle, and
      transcription. BRD4 and its family members contain two bromodomains known to bind
      acetylated lysine, and a conserved ET domain whose function is unclear. Here we
      show the solution structure of the ET domain of mouse BRD4, which provides the
      first three-dimensional structure of an ET domain in the BET family. We
      determined the NMR structure of BRD4-ET with a root-mean-square deviation of 0.41
      A for the backbone atoms in the structured region of residues 608-676 on the
      basis of 1793 upper distance limits derived from NOE intensities measured in
      three-dimensional NOESY spectra. The structure of the BRD4-ET domain comprises
      three alpha-helices and a characteristic loop region of an irregular but well
      defined structure. A DALI search revealed no close structural homologs in the
      current Protein Data Bank. The BRD4-ET structure has an acidic patch that forms a
      continuous ridge with a hydrophobic cleft, which may interact with other proteins
      and/or DNA.

PMID- 18815418
TI  - Full or partial hypermetropic correction for accommodative esotropia: does it
      matter?

PMID- 18815419
TI  - Cover illustration. Abu Bakr Razi.

PMID- 18815421
TI  - Emergence of diplopia and oscillopsia due to Heimann-Bielschowsky phenomenon
      after cataract surgery.
AB  - The Heimann-Bielschowsky phenomenon (HBP) refers to coarse vertical oscillation
      of the eye with impaired vision. The ocular movements are strictly monocular,
      occurring only in the eye with amblyopia. The vertical oscillation is of equal
      velocity in both vertical directions, or may sometimes be greater in the downward
      than upward direction. HBP develops several years after loss of vision. It can be
      differentiated from dissociated nystagmus in spasmus nutans, congenital nystagmus
      and internuclear ophthalmoplegia based on the strict unilaterality, vertical
      direction and low frequency. Previously, only a few reports described the
      development of oscillopsia due to HBP after cataract surgery, which resolved
      spontaneously or responded to gabapentin. However, visual impairments due to
      diplopia or oscillopsia from HBP after cataract surgery have received little
      attention. We report a man who developed persistent vertical diplopia and
      oscillopsia due to HBP after a cataract operation, which markedly impaired his
      vision.

PMID- 18815422
TI  - Cicatrising conjunctivitis with anti-basement membrane autoantibodies in
      ectodermal dysplasia.
AB  - AIMS: To report circulating and mucosa-deposited anti-basement membrane zone
      autoantibodies in a series of six ectodermal dysplasia patients with severe
      bilateral cicatrising conjunctivitis and blindness due to both corneal disease
      and intractable surface inflammation. We also report clinical improvement with
      steroid-sparing systemic immunosuppression combined with clearance of bacterial
      colonisation. METHODS: Conjunctival and buccal immunohistopathology, and
      serological analysis using a panel of epithelial basement membrane zone proteins
      including the bullous pemphigoid antigen 180 (BP180) were carried out as part of
      an ocular pemphigoid work-up in each patient. The degree of photophobia,
      conjunctival inflammation and visual acuity were monitored to evaluate the
      response to immunosuppression. The mean duration of follow-up was 31 (SD 6)
      months. RESULTS: Four of the six patients showed positive immunopathology: direct
      immunofluorescence testing of the conjunctiva in one patient demonstrated linear
      IgA deposition along the basement membrane zone, and IgG and IgM in the buccal
      mucosa of another patient. Circulating autoantibodies to BP180 were detected in
      two other patients. Treatment with systemic immunosuppression, combined with
      clearance of bacterial colonisation, reduced the severity of photophobia and
      degree of conjunctival inflammation in 5/6 (83%) patients. CONCLUSIONS: Systemic
      immunosuppression, used as steroid-sparing therapy, combined with clearance of
      bacterial colonisation can control inflammation and disabling photophobia, and
      allow improvement in vision, in a subgroup of ectodermal dysplasia patients who
      have severe cicatrising conjunctivitis which shares clinical and
      immunopathological features with ocular mucous membrane pemphigoid.

PMID- 18815423
TI  - The elasticity and rigidity of the outer coats of the eye.
AB  - AIMS: The aim of this study was to measure the elastic moduli of the cornea and
      sclera and the rigidity of the eyeball. METHODS: Elastic moduli of the cornea and
      sclera were measured on 22 fresh intact porcine eyes using the relationship
      between elasticity and changes in pressure and volume applicable to pressure
      vessel models. Rigidity was determined from the relationship between changes in
      volume and intraocular pressure (IOP). Induced volume changes were up to 300 mul
      and within the physiological range of IOP (12-25 mm Hg). IOP readings taken with
      a transducer were used in calculations. Tonometric values were taken for
      comparison. RESULTS: For cornea and sclera, the relationship between
      circumferential stress and volumetric strain (which defines the elastic modulus)
      was closely approximated to linear (R(2) = 0.96), but better fitted with a second
      order polynomial (R(2) = 1.00). Elastic moduli ranged from 0.05 to 0.24 MPa and
      0.15 to 0.83 MPa for the cornea and sclera, respectively. The mean value of
      ocular rigidity was found to be 0.0024. The effect of increasing IOP on the
      average corneal radius of curvature was not statistically significant, but it
      altered the scleral radius of curvature by 0.07 mm/mmHg. CONCLUSION: The
      elasticity of the porcine cornea and sclera could be approximated to constant
      over the physiological range, but showed a tendency to non-linearity. The modulus
      of elasticity for the sclera is 3 to 3.5 times that of the cornea. The cornea is
      more resistant than the sclera to IOP changes within the physiological range.

PMID- 18815424
TI  - Novel splice donor site mutation in MERTK gene associated with retinitis
      pigmentosa.
AB  - BACKGROUND/AIM: Mutations in MERTK, a member of the MER/AXL/TYRO3 receptor kinase
      family, have been associated with disruption of the Retinal Pigment Epithelium
      (RPE) phagocytosis pathway and settling of autosomal recessive RP (arRP) in
      humans. This study reports a novel MERTK mutation (IVS16+1G>T) in a Spanish
      consanguineous family presenting arRP. METHODS: 21 genes were screened by high
      throughput SNP multiplexing assay. Subsequent direct sequencing was performed in
      exons and intronic boundaries of the cosegregating gene. The effect of the
      mutation in mRNA splicing was confirmed by cDNA analysis. RESULTS: Haplotypic
      data revealed MERTK cosegregation with RP in affected individuals. MERTK
      sequencing showed a G-to-T substitution at the first nucleotide of intron 16.
      Finally, cDNA analysis confirmed the lack of exon 16 in the mRNA splicing
      process. CONCLUSIONS: IVS16+1G>T disrupts the splice donor site causing exon 16
      skipping. Absence of exon 16 causes a frameshift and, subsequently, the
      introduction of a premature termination codon into exon 17 creating an altered
      mRNA transcript with a seriously affected tyrosine kinase domain.

PMID- 18815425
TI  - Immunohistochemical localisation of intravitreally injected bevacizumab at the
      posterior pole of the primate eye: implication for the treatment of retinal vein
      occlusion.
AB  - AIM: To locate bevacizumab in the posterior pole within 1-14 days after
      intravitreal injection in the primate eye. METHODS: Four Cynomolgus monkeys
      received an intravitreal injection of 1.25 mg of bevacizumab. The eyes were
      enucleated on days 1, 4, 7 and 14 for immunohistochemistry using donkey anti
      human Cy3-IgG. Control eyes remained untreated. RESULTS: In the optic nerve,
      immunoreactivity for bevacizumab was most prominent on day 1 after injection and
      diminished rapidly. In the blood vessels of the nerve fibre layer, the staining
      was intense in the walls and weak in the lumen from day 1 to 4, and was only
      localised in the lumen thereafter. In the macula, an accumulation of bevacizumab
      was observed 1 day after injection in the nerve fibre layer, the ganglion cell
      layer and in the photoreceptors at the level of the outer nuclear layer in the
      fovea centralis. CONCLUSION: Bevacizumab penetrates quickly into the macula, the
      retinal veins and the optic nerve after intravitreal injection in the primate
      eye, and accumulates preferentially and specifically on the vessel walls and
      inside the photoreceptors localised in the fovea centralis 1 day after injection.
      Our finding supports the clinically observed rapid effect in the treatment of
      retinal vein occlusion and macular oedema.

PMID- 18815426
TI  - Keratocyte apoptosis increases in human corneal allografts during immune-mediated
      graft rejection.

PMID- 18815427
TI  - Idiopathic intracranial hypertension and congenital ocular melanocytosis: a new
      association.

PMID- 18815428
TI  - Efficacy of intravitreal bevacizumab as adjunctive treatment with pars plana
      vitrectomy, endolaser photocoagulation, and trabeculectomy for neovascular
      glaucoma.

PMID- 18815429
TI  - Suprachoroidal fluid as a complication of 23-gauge vitreous surgery.

PMID- 18815430
TI  - Sulfation patterns of keratan sulfate in different macular corneal dystrophy
      immunophenotypes using three different probes.

PMID- 18815432
TI  - Learning disability: challenging behaviour.

PMID- 18815433
TI  - Fifty years of advances in bile acid synthesis and metabolism.
AB  - There are two major pathways that mammalian cells use to supply themselves with
      cholesterol, one involving the synthesis of sterols from acetyl-CoA and the other
      the metabolism of cholesterol-rich lipoprotein particles via receptor-mediated
      endocytosis. There also are several pathways that mammalian cells use to break
      down cholesterol, and these disposal pathways are equal in physiological
      importance to the supply pathways. A major catabolic route involves conversion of
      cholesterol into conjugated bile salts, a transformation mediated by 16 or more
      liver enzymes. This review highlights findings in cholesterol catabolism from the
      last five decades with special emphasis on advances in bile acid synthesis,
      transport, and regulation.

PMID- 18815434
TI  - TNF-{alpha} plays a role in hepatocyte apoptosis in Niemann-Pick type C liver
      disease.
AB  - Niemann-Pick type C (NPC) is a fatal autosomal recessive lysosomal storage
      disease clinically characterized by neurodegeneration and liver disease.
      Heterogeneous mutations in the NPC1 and NPC2 genes cause impaired egress of free
      cholesterol from lysosomes, leading to accumulation of cholesterol and
      glycosphingolipids. Key features of NPC liver disease include hepatic apoptosis,
      inflammation, and fibrosis. It is unclear what signaling events regulate these
      disease processes in NPC. We hypothesize that tumor necrosis factor alpha (TNF
      alpha), which is involved in both proinflammatory and apoptotic signaling
      cascades, is a key mediator of inflammation, apoptosis, and fibrosis in NPC liver
      disease. In this study, we evaluated the role of TNF-alpha signaling in NPC liver
      disease by utilizing NPC1-specific antisense oligonucleotides to knock down NPC1
      expression in control and TNF-alpha knockout mice. In the absence of TNF-alpha,
      NPC1 knockdown produced liver disease with significantly less inflammation,
      apoptosis, and fibrosis.

PMID- 18815435
TI  - Chylomicrons promote intestinal absorption of lipopolysaccharides.
AB  - Recent data suggest that dietary fat promotes intestinal absorption of
      lipopolysaccharides (LPS) from the gut microflora, which might contribute to
      various inflammatory disorders. The mechanism of fat-induced LPS absorption is
      unclear, however. Intestinal-epithelial cells can internalize LPS from the apical
      surface and transport LPS to the Golgi. The Golgi complex also contains newly
      formed chylomicrons, the lipoproteins that transport dietary long-chain fat
      through mesenteric lymph and blood. Because LPS has affinity for chylomicrons, we
      hypothesized that chylomicron formation promotes LPS absorption. In agreement
      with our hypothesis, we found that CaCo-2 cells released more cell-associated LPS
      after incubation with oleic-acid (OA), a long-chain fatty acid that induces
      chylomicron formation, than with butyric acid (BA), a short-chain fatty acid that
      does not induce chylomicron formation. Moreover, the effect of OA was blocked by
      the inhibitor of chylomicron formation, Pluronic L-81. We also observed that
      intragastric triolein (TO) gavage was followed by increased plasma LPS, whereas
      gavage with tributyrin (TB), or TO plus Pluronic L-81, was not. Most intestinally
      absorbed LPS was present on chylomicron remnants (CM-R) in the blood. Chylomicron
      formation also promoted transport of LPS through mesenteric lymph nodes (MLN) and
      the production of TNFalpha mRNA in the MLN. Together, our data suggest that
      intestinal epithelial cells may release LPS on chylomicrons from cell-associated
      pools. Chylomicron-associated LPS may contribute to postprandial inflammatory
      responses or chronic diet-induced inflammation in chylomicron target tissues.

PMID- 18815436
TI  - Highly sensitive quantification of key regulatory oxysterols in biological
      samples by LC-ESI-MS/MS.
AB  - We describe a highly sensitive and specific method for the quantification of key
      regulatory oxysterols in biological samples. This method is based upon a stable
      isotope dilution technique by liquid chromatography-tandem mass spectrometry (LC
      MS/MS). After alkaline hydrolysis of human serum (5 microl) or rat liver
      microsomes (1 mg protein), oxysterols were extracted, derivatized into picolinyl
      esters, and analyzed by LC-MS/MS using the electrospray ionization mode. The
      detection limits of the picolinyl esters of 4beta-hydroxycholesterol, 7alpha
      hydroxycholesterol, 22R-hydroxycholesterol, 24S-hydroxycholesterol, 25
      hydroxycholesterol, 27-hydroxycholesterol, and 24S,25-epoxycholesterol were 2-10
      fg (5-25 amol) on-column (signal-to-noise ratio = 3). Reproducibilities and
      recoveries of these oxysterols were validated according to one-way layout and
      polynomial equation, respectively. The variances between sample preparations and
      between measurements by this method were calculated to be 1.8% to 12.7% and 2.9%
      to 11.9%, respectively. The recovery experiments were performed using rat liver
      microsomes spiked with 0.05 ng to 12 ng of oxysterols, and recoveries of the
      oxysterols ranged from 86.7% to 107.3%, with a mean recovery of 100.6%. This
      method provides reproducible and reliable results for the quantification of
      oxysterols in small amounts of biological samples.

PMID- 18815437
TI  - Do attention deficits influence IQ assessment in children and adolescents with
      ADHD?
AB  - OBJECTIVE: To characterize the relationship between IQ and attention deficits in
      children with ADHD and to estimate the inattention-related mean influence on IQ
      when children are tested before stimulant drug treatment has been initiated.
      METHOD: Studies of various methodologies are reviewed. RESULTS: Correlation
      studies show mostly weak associations between IQ scores and attention deficits.
      Meta-analyses report the average short-term stimulant treatment effect on IQ in
      children with ADHD to be 2 to 7 IQ points. CONCLUSION: The associations between
      IQ and attention deficits in ADHD are generally modest, with the mean influence
      on IQ probably amounting to 2 to 5 IQ points. This may serve as a benchmark when
      clinicians interpret the validity of IQ in this clinical population.

PMID- 18815438
TI  - Simulated driving changes in young adults with ADHD receiving mixed amphetamine
      salts extended release and atomoxetine.
AB  - BACKGROUND: Psychostimulant treatment may improve simulated driving performance
      in young adults with attention-deficit/hyperactivity disorder (ADHD). METHOD:
      This was a randomized, double-blind, placebo-controlled, crossover study of
      simulated driving performance with mixed amphetamine salts-extended release (MAS
      XR) 50 mg/day (Cohort 1) and atomoxetine 80 mg/day (Cohort 2) in young adults
      with ADHD. RESULTS: Adults aged 19 to 25 years with AD/HD (N = 19) who were
      administered MAS XR significantly improved overall simulated driving performance
      versus placebo up to 12 hours after dosing. In contrast, there were no
      statistically significant differences in simulated-driving-performance scores
      between atomoxetine and placebo. At endpoint, MAS XR reduced ADHD Rating Scale
      scores > or = 30% in 80% of subjects, whereas atomoxetine achieved this level of
      improvement for 40%. LIMITATIONS: Small sample size and use of simulated driving
      may limit generalizability of the findings. CONCLUSION: MAS XR in young adults
      with ADHD yields significant improvements in simulated driving performance and
      ADHD symptoms.

PMID- 18815439
TI  - Cell derived hierarchical assembly of a novel phosphophoryn-based biomaterial.
AB  - Phosphophoryn (PP) is an acidic phosphoprotein belonging to the small integrin
      bindingligand N-linked glycoprotein (SIBLING) protein family. PP is highly
      phosphorylated with approximately 200 phosphates per molecule and has a high
      affinity for calcium. The aim of this manuscript is to demonstrate that PP has
      the ability to self-assemble when it is overexpressed in a mammalian cell in the
      presence of calcium. Our data show that when PP is overexpressed using an
      adenovirus, the self-assembly occurs in the endoplasmic reticulum (ER) which
      contains high calcium concentration. We hypothesize that the physicochemical
      properties of the highly phosphorylated state and acidic nature of PP are playing
      an important role in its assembly in the ER. It appears that when a critical
      concentration of PP is reached, the assembly is then favored and facilitated.
      This self-assembly could be due to several factors. (1) The ER provides an ideal
      environment for this phenomenon to occur, since the ER environment usually
      promotes aggregation [Stevens and Argon: Semin Cell Dev Biol 1999;10:443-454].
      (2) In addition to PP's physicochemical properties, the unfolded protein response
      could also be playing a role in this self-assembly [Schroder and Kaufman: Mutat
      Res 2005;569:29-63]. Unfolded protein response could be activated by a broad
      spectrum of insults that result in protein misfolding and ultimately blocking of
      the protein synthesis progression to the Golgi apparatus resulting in an
      accumulation of the protein in the ER. In summary, our data show that PP has the
      ability to self-assemble in a hierarchical manner.

PMID- 18815440
TI  - Hippocampal estrogen receptor-alpha splice variant TADDI in the human brain in
      aging and Alzheimer's disease.
AB  - BACKGROUND/AIMS: Estrogen receptor-alpha (ER alpha) splice variants are important
      for understanding estrogen effects on the brain and estrogen therapy pitfalls. We
      addressed the question whether a novel ER alpha splice variant TADDI is expressed
      at the protein level in the human brain and whether it changes in relation to
      aging and Alzheimer's disease (AD). METHODS: Immunoreactivity (-ir) for TADDI was
      assessed on postmortem human brain material from a total of 116 cases. RESULTS:
      The highest levels of this splice form were found in the hypothalamic supraoptic
      nucleus (SON), pontine nuclei, medulla oblongata, gray matter of the spinal cord,
      the hippocampus, glomeruli of the cerebellum, the nucleus basalis of Meynert
      (NBM), and the tuberomamillary nucleus (TMN). TADDI-ir was mainly confined to the
      cytoplasm but was also determined in the nuclei of hippocampal neurons from young
      patients. In the hippocampus, the NBM, and the TMN, TADDI-ir was higher in
      postmenopausal women than in women <or=50 years old. In these brain areas and in
      the SON, it was diminished in AD women. In the NBM of AD men, TADDI-ir was
      enhanced. CONCLUSION: Aging- and AD-related changes in TADDI-ir show that it
      should be considered for the sensitivity of the neural tissue to estrogen
      therapy.

PMID- 18815441
TI  - Expression of collagen types I, II and III in juvenile angiofibromas.
AB  - Extracellular matrix components have rarely been the focus of interest in
      juvenile angiofibroma (JA) studies. Although JAs are known to be collagen-rich
      tumours, single collagens have not been analysed so far. This investigation aimed
      to study the expression of the fibrillar collagen types I, II and III in JAs
      using quantitative RT-PCR (n = 15), Western blot analysis (n = 7) and
      immunohistochemical staining (n = 9). Nasal mucosa (NM) specimens were used as
      control tissues. ELISA investigation (n = 3) was performed to determine the
      concentration of C-terminal propeptide of type I collagen in blood serum before
      and after JA resection. Quantitative RT-PCR found significantly elevated Col1A1
      (p < 0.001), Col1A2 (p < 0.001) and Col3A1 (p < 0.001) mRNA levels in JAs,
      compared with NM. Western blot analysis and immunohistochemical staining proved
      that there is a significant collagen type I and III protein expression in JAs. In
      none out of 3 patients, ELISA investigation found evidence for elevated
      concentrations of C-terminal propeptide of type I collagen before tumour
      resection, compared with postsurgical measurements. Results of the findings using
      quantitative RT-PCR, Western blot analysis and immunohistochemistry determined
      that type II collagen is practically absent in JAs. Based on these findings, type
      I and III collagen are confirmed as being major components of the extracellular
      matrix in JAs. However, our findings are not encouraging as regards the use of C
      terminal Col I propeptide as a suitable serum tumour marker. Our findings
      confirming that collagen type II expression is practically absent in JAs refutes
      the theory that JAs originate in cartilage tissue.

PMID- 18815442
TI  - Organization of projection-specific interneurons in the spinal cord of the red
      eared turtle.
AB  - Using differential retrograde axonal tracing, we identified motoneurons (MNs) and
      projection-specific interneuron (IN) classes in lumbar segment D9 of the adult
      red-eared turtle spinal cord. We characterized the distribution of these neurons
      in the transverse plane, and estimated their numbers and proportions. Different
      labeling paradigms allowed us to distinguish ipsilateral INs (IINs) from
      commissural INs (CINs), and to identify IINs and CINs with either ascending (a)
      axons, descending (d) axons, or axons that bifurcate to both ascend and descend
      (ad). Local interneurons with axons shorter than 1 segment in length were not
      studied. We show that most retrogradely labeled INs are located dorsal to the
      MNs, in the ventral horn, the intermediate zone and the dorsal horn. IINs
      predominate in the dorsal horn. CINs are located on average more medially than
      the IINs in the ventral horn and intermediate zone. Within the IIN and CIN
      populations, aINs and dINs overlap extensively. The adIINs and adCINs make up
      only a small fraction of the total number of INs and are scattered throughout
      much of the respective IIN and CIN domains. The proportions of IINs and CINs are
      about equal, as are the proportions of aIINs versus dIINs, of aCINs versus dCINs,
      and of adIINs versus adCINs. The findings are compared to the organization of
      lumbar spinal INs in other vertebrate species.

PMID- 18815443
TI  - Comparative study of TPep-like immunoreactive neurons in the central nervous
      system of nudibranch molluscs.
AB  - In the sea slug Tritonia diomedea, mucociliary crawling is controlled partly by
      two pairs of bilaterally symmetrical neurons located in the pedal ganglia. These
      neurons, known as the Pedal 5 and Pedal 6 cells, produce a class of neuropeptides
      called TPeps. Using immunohistochemistry we identified TPep-like immunoreactive
      (TPep-LIR) neurons in diverse nudibranch species. All species examined had 2-7
      large, TPep-LIR cells located in each pedal ganglion. The absolute size of the
      largest TPep-LIR neuron was correlated with foot size. Species with a bigger foot
      size tended to have larger TPep-LIR cells. However, the number of cells in a
      given species was not correlated with the size of the adult foot. The presence of
      large, TPep-LIR cells across the nudibranchs suggests that part of the neural
      circuitry controlling mucociliary locomotion has been conserved, although the
      size and number of cells is variable across species. We conclude that the motor
      circuit underlying crawling might adapt to changes in foot size by changing the
      size of motor neurons in the circuit, but that changes in cell number are not
      directly related to foot size.

PMID- 18815444
TI  - Noradrenergic deficits alter processing of communication signals in female
      songbirds.
AB  - During acoustic communication, animals must attend to sounds from a particular
      source while simultaneously rejecting intrusion from other sources. One possible
      candidate mechanism for this process is the noradrenergic system. Noradrenaline
      is a neuromodulator that tunes sensory processing systems and regulates
      attention. We examined whether pharmacological degradation of the noradrenergic
      system using N-(2-chloroethyl)-N-2-bromobenzyl-amine hydrochloride (DSP-4)
      modifies processing of species-typical auditory signals in female canaries
      (Serinus canaria). We measured auditory responses to conspecific and
      heterospecific songs using ZENK protein expression within the caudomedial
      nidopallium (NCM) and the mesopallium caudomedial (CMM). Song-induced ZENK
      expression in these auditory forebrain areas is typically higher in birds exposed
      to conspecific songs as opposed to heterospecific songs. Our results reveal that
      this differential ZENK induction is abolished specifically within dNCM and CMM in
      female canaries treated with DSP-4. Furthermore, in DSP-4-treated birds,
      conspecific song-induced ZENK expression is significantly reduced when compared
      to saline-treated birds. This suggests that the noradrenergic system modifies
      auditory processing by enhancing neuronal responses to signals relevant to
      survival and reproduction rather than inhibiting neuronal responses to signals
      that are less relevant. Overall, our results reveal that noradrenaline plays a
      significant neuromodulatory role during the reception of species-typical
      communication signals.

PMID- 18815445
TI  - Treatment of stable atrial fibrillation in the emergency department: a population
      based comparison of electrical direct-current versus pharmacological
      cardioversion or conservative management.
AB  - OBJECTIVE: To compare the success rates and short-term complications of three
      treatment approaches, pharmacological and direct-current cardioversion (DCC), or
      'wait-and-watch' among stable atrial fibrillation (AF) patients in the emergency
      department (ED). METHODS: All AF-related ED admissions during a 1-year period
      were retrospectively reviewed, and those meeting criteria of eligibility for
      immediate cardioversion, based on clinical stability, AF duration and adequacy of
      anticoagulation, were included. The propensity score approach generalized for the
      three groups was used to adjust for the observational non-randomized study
      nature. RESULTS: Among 374 eligible patients, the rate of successful
      cardioversion was higher in DCC than in pharmacological or wait-and-watch groups
      (78.2, 59.2 and 37.9% respectively, p < 0.001), with corresponding percentages of
      patients discharged from ED (52.9, 47.9 and 32.1%, p < 0.01) and respective odds
      ratios of 6.00, 2.47 and 1, adjusting for seniority of the treating physician,
      age, gender and patient comorbidities. DCC was 2.43 times more effective than
      pharmacological treatment in achieving sinus rhythm (95% confidence interval =
      1.36-4.33, p = 0.003). Rehospitalization within 14 days due to probable AF
      treatment-related complications of home-discharged patients was 3.4%.
      CONCLUSIONS: DCC was found to be the most effective treatment, with few short
      term complications following conversion of stable AF patients to sinus rhythm in
      the ED.

PMID- 18815446
TI  - Berberine-induced upregulation of circulating endothelial progenitor cells is
      related to nitric oxide production in healthy subjects.
AB  - OBJECTIVES: Berberine (BR) has a beneficial effect on endothelial function by
      increasing nitric oxide (NO), as NO plays a pivotal role in the regulation of
      endothelial progenitor cell (EPC) mobilization and function. The aim of the
      present study was to investigate whether BR-induced upregulation of circulating
      EPCs is related to NO production in healthy subjects. METHODS: Twenty volunteers
      were recruited and received 400 mg of BR 3 times a day for 30 days. We assessed
      the number of EPC colony-forming units (EPC-CFUs), as well as the proliferative,
      adhesive and migratory activities of circulating EPCs before and after the 30-day
      BR therapy. The level of plasma NO was also measured before and after the 30-day
      BR therapy. RESULTS: After 30 days of BR therapy, the number of EPC-CFUs was
      increased and the function of EPCs, including proliferation, adhesion and
      migration, was augmented. In parallel, BR therapy enhanced the plasma NO level.
      There was a significant linear regression relationship between the enhanced
      plasma NO level and the increased number and function of circulating EPCs.
      CONCLUSIONS: BR-induced upregulation of the number and function of circulating
      EPCs in healthy subjects is related to NO production.

PMID- 18815447
TI  - Systemic and local cytokine kinetics after total hip replacement surgery.
AB  - BACKGROUND: Trauma induces local and subsequent systemic inflammatory reactions.
      Aberrant reactions can lead to a systemic inflammatory response syndrome, with a
      potentially lethal outcome. Our aim was to investigate the early local cytokine
      kinetic compared to systemic changes in a standardized surgical trauma. METHODS:
      In 7 patients with total hip replacement, drained blood samples and venous blood
      samples were taken 3 times within the first day after the operation. Interleukin
      (IL) release was assessed by a multiplex antibody bead kit and compared to pre
      operative values. RESULTS: The major findings were significant increases in
      systemic levels of IL-6 and in local levels of IL-6, IL-8 and IL-1 receptor
      antagonist (IL-1Ra), and that the local levels of these cytokines were
      significantly higher than the systemic ones after surgery. Besides, there were
      only modest changes in local and systemic levels of tumour necrosis factor alpha,
      IL-1 beta, IL-2, IL-2Ra, IL-4, IL-5, IL-7, IL-10, IL-12, IL-13, IL-15 and IL-17.
      CONCLUSIONS: The acute sterile inflammation after major orthopaedic surgery is
      principally characterized by significantly increased local and systemic levels of
      IL-6 and significantly increased local levels of IL-8 and IL-1Ra. Furthermore,
      the concentrations are higher at the local site of injury. Hence, we conclude
      that systemic cytokine levels might not reflect local reactions.

PMID- 18815449
TI  - Association between changes in N-terminal pro-brain natriuretic peptide levels
      and changes in left ventricular mass index in stable hemodialysis patients.
AB  - BACKGROUND/AIMS: Left ventricular (LV) hypertrophy is a powerful predictor of
      mortality in dialysis patients. Serial measurements of LV mass provide prognostic
      information. We evaluated the association between changes in biomarkers and
      changes in LV mass index (LVMI) in hemodialysis (HD) patients. METHODS: This was
      a prospective study of 21 stable HD patients with preserved LV ejection fraction
      (> or =50%). Echocardiography and measurements of N-terminal pro-brain
      natriuretic peptide (NT-proBNP), brain natriuretic peptide (BNP) and cardiac
      troponin T were performed on the same day and repeated 6 and 12 months later.
      RESULTS: At baseline, the NT-proBNP and BNP levels correlated with LVMI. Percent
      changes in LVMI were positively associated with those in log-transformed NT
      proBNP levels during both the first (baseline vs. month 6, r = 0.78, p < 0.001)
      and the second 6 months (months 6 vs. 12, r = 0.73, p < 0.001). Among the 3
      biomarkers, NT-proBNP was the only one that was related to changes in LVMI by
      multivariate correlation analysis, including age, sex, blood pressure,
      predialysis weight and use of angiotensin-converting enzyme inhibitor or
      angiotensin II receptor blocker. CONCLUSION: Our results show that changes in
      LVMI are closely correlated with variation in NT-proBNP levels in HD patients.
      These data have significant implications for the application of NT-proBNP as a
      biomarker for assessing changes in LVMI in HD patients.

PMID- 18815450
TI  - Modifier effect of the Glu298Asp polymorphism of endothelial nitric oxide
      synthase gene in autosomal-dominant polycystic kidney disease.
AB  - Autosomal-dominant polycystic kidney disease (ADPKD) is one of the most common
      monogenic diseases. It is characterized by a substantial variability in the
      severity of renal phenotype, primarily assessed by the age at end-stage renal
      disease (ESRD). The role of modifier genes has been shown in various hereditary
      diseases, including ADPKD. The gene coding for the endothelial nitric oxide
      synthase (NOS3) is considered to have a modifier effect on the severity of ADPKD,
      even if there are studies among different populations that have shown
      contradictory results. In this study, we investigated the influence of one of the
      most studied polymorphisms of the NOS3 gene, the Glu298Asp polymorphism, on the
      age at ESRD in ADPKD. We analyzed a total of 100 ADPKD unrelated patients and 107
      healthy cohorts from the Greek population. ADPKD patients were classified into
      two subgroups: patients with early (rapid progressors) and late (slow
      progressors) age at ESRD. The results suggested that the Glu298Asp polymorphism
      of NOS3 gene is associated with the onset age of ESRD. The distribution of C/T
      alleIes is significantly different between rapid and slow ADPKD progressors
      leading to the conclusion that the T allele of the Glu298Asp polymorphism of NOS3
      gene is associated with earlier progression to ESRD in ADPKD patients.

PMID- 18815451
TI  - Evaluation of the impact of memantine treatment initiation on psychotropics use:
      a study from the French national health care database.
AB  - BACKGROUND: Clinical studies reported that treatments for Alzheimer's disease may
      have an impact on behavioral and psychiatric disorders. We tested the hypothesis
      that memantine treatment initiation modifies psychotropic medication in real-life
      practice patients. METHODS: A 2-year follow-up cohort study was performed. A
      sample of patients treated in the general population, extracted from the database
      of the French national healthcare system (CNAM-TS), was examined. The sample
      included 4,600 memantine-treated patients (mean age 79.8 years, 69% women)
      randomly selected from the database of the CNAM-TS covering 69% of the French
      population aged 65 years and over. The follow-up rate was 95.0%. This database
      includes exhaustive data on drug consumption. We used interrupted time series
      analysis of the proportion of psychotropics users (all psychotropic drugs and
      specific categories) before and after onset of memantine. RESULTS: There was a 39
      50% regular increase in patients treated with psychotropic drugs before memantine
      initiation This increasing trend stopped after memantine initiation, the
      proportion of psychotropic users remaining stable around 53% up to the end. The
      trends before and after memantine onset were significantly different (p < 0.001).
      CONCLUSIONS: Our results suggest a temporal relationship between the onset of
      memantine and the stabilization of psychotropic drugs use in this large sample of
      elderly patients.

PMID- 18815452
TI  - Loss of the sense of self-ownership for perceptions of objects in a case of right
      inferior temporal, parieto-occipital and precentral hypometabolism.
AB  - Philosophers define the 'minimal self' as the immediate awareness of being the
      agent and owner of one's actions and perceptions. Here, we describe a patient
      with a selective loss of one part of this 'minimal self', namely the immediate
      sense of self-ownership for perceptions of objects. In contrast, his sense of
      self-ownership for body perceptions and for self-agency during actions remained
      intact. 18-Fluorodeoxyglucose positron emission tomography revealed predominantly
      right inferior temporal hypometabolism in comparison with healthy controls
      (parahippocampal and fusiform gyri). In addition, dysfunction of the right
      parieto-occipital junction and precentral cortex were detected. Taken together,
      we demonstrate selective changes in the quality of the sense of self-ownership
      for perceptions of objects but not actions and an intact sense of self-agency,
      which points to anatomically separable systems underpinning different aspects of
      the 'minimal self'. The associated hypometabolism in inferior temporal, parieto
      occipital and motor regions, but not in medial prefrontal areas most consistently
      associated with self-referential processing, are most parsimoniously explained
      when self-consciousness is not assumed to be an anatomically localized cognitive
      function, but instead is conceived as emerging from integration across
      anatomically distributed networks of regions with different functional
      specializations, not all of which need to be special for the 'self'.

PMID- 18815453
TI  - [Anti-tumor mechanisms and regulation of survivin by selective cyclooxygenase-2
      inhibitor].

PMID- 18815454
TI  - [Clinical application of stem cells in liver diseases].
AB  - Most liver diseases lead to hepatic dysfunction with organ failure. Liver
      transplantation is the best curative therapy, but it has some limitations such as
      donor shortage, possibility of rejection, and maintenance of immunosuppressant.
      New therapies have been actively searched for over several decades, primarily in
      the form of artificial liver support devices and hepatocyte transplantation, but
      both of these modalities remain experimental. Stem cells have recently shown
      promise in cell therapy because they have the capacity for self-renewal and
      multilineage differentiation, and are applicable to human diseases. Very recent
      reports of unexpected plasticity in adult bone marrow have raised hopes of stem
      cell therapy offering exciting therapeutic possibilities for patients with
      chronic liver disease. Both rodent and human embryonic stem cells, bone marrow
      hematopoietic stem cells, mesenchymal stem cells, umbilical cord blood cells,
      fetal liver progenitor cells, adult liver progenitor cells, and mature
      hepatocytes have been reported to be capable of self-renewal, giving rise to
      daughter hepatocytes both in vivo and in vitro. These cells can repopulate livers
      in animal models of liver injury and appear to be able to improve liver function.
      However, significant challenges still exist before these cells can be used in
      humans, such as the lack of consensus about the immunophenotype of liver
      progenitor cells, uncertainty of the physiological role of reported candidate
      stem/progenitor cells, practicality of obtaining sufficient quantity of cells for
      clinical use, and concerns over ethics, long-term efficacy, and safety. There
      have been reports of phase 1 trials using stem cell transplantation in humans for
      liver diseases, but more effective trials are needed. We review the use of stem
      cells (focusing on adult ones) and the reported human clinical trials, and
      highlight the challenges facing clinicians in their quest to use liver stem cells
      to save lives.

PMID- 18815455
TI  - [Effects of pegylated interferon and ribavirin in Korean patients with chronic
      hepatitis C virus infection].
AB  - BACKGROUND/AIMS: We assessed the efficacy and safety of pegylated interferon
      (peginterferon) plus ribavirin and identified the predictors of a sustained
      virologic response (SVR) in Korean patients with chronic hepatitis C virus
      infection. METHODS: A total of 192 patients with chronic hepatitis C, treated
      with both peginterferon (n=141) or conventional interferon (n=51) and ribavirin,
      were analyzed retrospectively. Peginterferon alfa-2a (180 microgram/week) or -2b
      (1.5 microgram/kg/week) or interferon alfa-2a (3 MIU thrice weekly) was
      administered in combination with ribavirin at 1,000-1,200 mg/day for 48 weeks for
      genotype 1 and at 800 mg/day for 24 weeks for genotypes 2 and 3. RESULTS: The
      overall SVR rate was 80.9% (114/141) in the peginterferon group and 52.9% (27/51)
      in the interferon group (P=0.0001). The SVR rate in genotype 1 was 69.5% (41/59)
      in the peginterferon group and 31.6% (6/19) in the interferon group (P=0.0033),
      whereas in genotype 2 or 3 it was 89.0% (73/82) in the peginterferon group and
      65.6% (21/32) in the interferon group (P=0.0032). The predictors of SVR in the
      peginterferon group were genotype, absence of cirrhosis, and early virologic
      response (P<0.05). CONCLUSIONS: In Korean patients with chronic hepatitis C, a
      regimen of peginterferon and ribavirin was more effective than a regimen of
      conventional interferon and ribavirin. This result is comparable to those from
      studies on Western patients as an initial treatment for chronic hepatitis C.

PMID- 18815456
TI  - [Natural history of gastric varices and risk factors for bleeding].
AB  - BACKGROUND/AIMS: Gastric varices (GV) are one of the most serious complications
      of portal hypertension, but there is limited information on the clinical course
      of GV in Korea. The aim of this study was to elucidate the natural history of GV
      bleeding in Korean patients. METHODS: Of 604 patients with GV diagnosed between
      May 1995 and May 2005 at the Samsung Medical Center, 237 patients without a
      history of variceal bleeding or previous intervention for varices were
      investigated. The cumulative incidence rates of GV bleeding, long-term survival
      rates, and risk factors for GV bleeding were evaluated. RESULTS: The cumulative
      incidence rates of GV bleeding were 4.8%, 19.9%, and 23.2% at 1, 3, and 5 years
      after diagnosis, respectively. The overall survival rates were 88.6%, 53.2%, and
      37.2% at 1, 5, and 10 years. In the univariate analysis, fundal varices, large
      (F3) GV, red color sign, and poor liver function (Child-Pugh class B or C) were
      significant risk factors for GV bleeding. In the multivariate analysis, large GV
      (hazard ratio 2.49) and poor liver function (hazard ratio 3.95) were the
      independent risk factors. CONCLUSIONS: GV bleeding was more frequent in patients
      with fundal varices than in patients with type 1 gastroesophageal varices, and
      large GV and poor liver function were risk factors for GV bleeding. Close
      observation and prophylaxis for variceal bleeding might be warranted in high-risk
      patients.

PMID- 18815457
TI  - [Usefulness of liver stiffness measurement for predicting the presence of
      esophageal varices in patients with liver cirrhosis].
AB  - BACKGROUND/AIMS: Bleeding from esophageal varices (EV) is a major cause of death
      in patients with liver cirrhosis. Endoscopic screening is recommended for
      diagnosing EV, but various noninvasive parameters can also be used to predict EV.
      The liver stiffness measurement (LSM), a noninvasive technique for estimating
      liver fibrosis, was recently reported to be strongly correlated with the hepatic
      venous pressure gradient. This study evaluated the usefulness of LSM for
      predicting the presence and size of EV in patients with cirrhosis. METHODS: The
      relationships of LSM with the presence and size of EV were analyzed in 112
      patients with liver cirrhosis. Liver cirrhosis was diagnosed histologically or
      clinically. The presence and size of EV were assessed by endoscopy, and LSM was
      determined by the Fibroscan technique. RESULTS: LSM was strongly correlated with
      the presence of EV (P<0.0001): the LSM value was 42.7+/-21.9 kPa (mean+/-standard
      deviation) in patients with EV (n=82) and 19.1+/-12.6 kPa in patients without EV
      (n=30). The area under the receiver operating characteristic curve was 0.818 (95%
      CI, 0.732-0.904) for predicting the presence of EV, and an LSM value of 19.7 kPa
      was predictive of the presence of EV with a sensitivity of 87%, a specificity of
      70%, a PPV of 89%, and a NPV of 66%. However, there was a weak correlation
      between LSM and the size of EV. CONCLUSIONS: LSM is useful for predicting the
      presence of EV in patients with cirrhosis but not their size.

PMID- 18815458
TI  - [Down-regulation of survivin in growth inhibition of hepatoma cells induced by a
      selective cyclooxygenase-2 inhibitor].
AB  - BACKGROUND/AIMS: Cyclooxygenase-2 (COX-2) inhibitors reportedly inhibit the
      growth of hepatocellular carcinoma (HCC) via caspase-dependent or caspase
      independent apoptosis, which is due to COX-2 being associated with
      hepatocarcinogenesis. Survivin is highly expressed in most human cancers, but the
      mechanism regulating survivin expression remains unclear. We investigated the
      regulatory expression of survivin in selective-COX-2-inhibitor-induced growth
      inhibition of hepatoma cells. METHODS: After treatment with NS-398 (a selective
      COX-2 inhibitor) at various concentrations (10, 50, 100, 150, and 200
      micrometer), the growth inhibition of Hep3B hepatoma cells was assessed by an MTT
      cell-viability assay, DNA fragmentation gel analysis, and flow cytometry. The
      expression of survivin transcript was analyzed by reverse-transcription
      polymerase chain reactions. RESULTS: NS-398 inhibited the growth of hepatoma
      cells by an amount dependent on the concentration and the time since treatment.
      Apoptotic DNA ladder and flow-cytometry shifting to the sub-G1 phase were
      revealed in NS-398-induced growth inhibition of hepatoma cells. NS-398 suppressed
      the expression of the survivin gene in a concentration- and time-dependent
      manner. CONCLUSIONS: Survivin was down-regulated in the growth inhibition of
      hepatoma cells induced by a selective COX-2 inhibitor, NS-398, in a concentration
      and time-dependent manner. These results suggest the therapeutic inhibition of
      COX-2 via suppression of survivin in HCC.

PMID- 18815459
TI  - [Clinical outcomes of systemic chemotherapy in hepatocellular carcinoma patients
      with multiple lung metastases].
AB  - BACKGROUND/AIMS: Advanced hepatocellular carcinoma (HCC) with multiple lung
      metastases has a poor prognosis with no effective treatment having been
      established. This study evaluated the outcomes of systemic chemotherapy for
      advanced HCC with multiple lung metastases. METHODS: Between January 2000 and
      December 2006, 68 patients were diagnosed with HCC presenting with multiple lung
      metastases. Sixteen patients in the terminal stage, such as Child-Pugh grade ;C'
      or an Eastern Cooperative Oncology Group performance status exceeding grade 2,
      were excluded from the analysis. The following treatment modalities were applied:
      26 patients received primary tumor treatment (transarterial chemoembolization or
      intra-arterial chemotherapy) with systemic chemotherapy, 10 patients received
      primary treatment only, 8 patients received systemic chemotherapy only, and 8
      patients received highly supportive care. The treatment responses and median
      survival times for the modalities were analyzed and compared. RESULTS: The median
      age of the 52 analyzed patients (45 males) was 52.4 years. The most common
      etiology of HCC was chronic hepatitis B virus infection (n=44, 84.6%) followed by
      hepatitis C virus infection (n=2, 3.8%), with the etiology being unknown in 6
      cases (11.5%). The treatment modality had no significant effect on the treatment
      response rate (P=0.432) or median survival time (133, 66, 74, and 96 days for
      primary tumor treatment with systemic chemotherapy, primary tumor treatment only,
      systemic chemotherapy only, and highly supportive care, respectively; P=0.067).
      CONCLUSIONS: We found that systemic chemotherapy was not effective in treating
      HCC presenting with multiple lung metastases. Improving the effectiveness of
      systemic treatment and selecting patients who would benefit from such treatment
      remains a major challenge.

PMID- 18815460
TI  - [Risk factors for early recurrence after surgical resection for hepatocellular
      carcinoma].
AB  - BACKGROUND/AIMS: Early recurrence (ER) after liver resection is one of the most
      important factors impacting the prognosis and survival of patients with
      hepatocellular carcinoma (HCC). This study aimed to identify the factors
      associated with ER after curative hepatic resection for HCC. METHODS: From the
      July 2000 to July 2006, 144 patients underwent hepatic resection for HCC at a
      single institution. After excluding those with ruptured HCC, combined or mixed
      HCC, and who died during admission, 116 patients were analyzed. Patients with ER
      (defined as within 1 year) were compared with those who remained free of disease
      for more than 1 year. Various clinical characteristics including tumor and
      operative factors were evaluated to determine the factors predicting
      postoperative ER using univariate and multivariate analyses. RESULTS: ER occurred
      in 51 patients (44%). In the univariate analysis, tumor size (P=0.001),
      microvascular invasion (P=0.003), portal vein invasion (P=0.001), TNM stage
      (P=0.010), serum levels of alpha-fetoprotein (AFP) (P=0.002) and aspartate
      aminotransferase (AST) (P=0.011), and operative time (P=0.033) were significantly
      associated with ER. AFP and AST were the independent predictors of ER in the
      multivariate analysis (P<0.05). CONCLUSIONS: Preoperative serum AFP and AST
      levels were the independent risk factors for ER after surgical resection for HCC.
      Close postoperative surveillance is recommended for early detection of recurrence
      and additional treatments in patients with these factors.

PMID- 18815461
TI  - [A case of severe hypophosphatemia related to adefovir dipivoxil treatment in a
      patient with liver cirrhosis related to hepatitis B virus].
AB  - Adefovir dipivoxyl (ADV) effectively suppresses hepatitis B virus (HBV)
      replication but exhibits nephrotoxicity with severe hypophosphatemia when
      administered at a high dosage. This is the first report of severe
      hypophosphatemic osteomalacia induced by ADV at 10 mg/day. A 42-year-old man with
      HBV-related chronic liver disease presented with generalized bone pain,
      especially in the left ankle. He had been taking ADV for more than 1.5 years
      following a clinical breakthrough due to lamivudine-resistant HBV. Aggravating
      severe hypophosphatemia and elevated serum alkaline phosphatase levels with high
      bone fraction had been noted after 6 months of ADV therapy. Bone densitometry,
      simple bone X-rays, and a whole-body bone scan demonstrated osteoporosis and
      multiple areas with hot uptake, especially in the left ankle. All the image
      findings and symptoms improved after correcting the hypophosphatemia.

PMID- 18815462
TI  - [Three cases of multiple infarcted regenerative nodules in liver cirrhosis after
      gastrointestinal hemorrhage].
AB  - An infarction of regenerative nodules in liver cirrhosis is a rare abnormality
      characterized by their coagulative necrosis. We presume that ischemic necrosis is
      induced by a sudden reduction in the portal and arterial blood flows after blood
      loss or shock. Most patients with infarcted regenerative nodules have experienced
      previous episodes of gastrointestinal hemorrhage. Awareness of the entity of
      infarcted regenerative nodules and its inclusion in the differential diagnosis of
      multiple hepatic nodules in liver cirrhosis is important, particularly in
      patients with an episode of gastrointestinal bleeding. The possible difficulty of
      differentiating infarcted regenerative nodules in liver cirrhosis from
      hypovascular hepatocellular carcinoma by initial imaging findings alone means
      that a liver biopsy and serial imaging might be helpful in the differential
      diagnosis. We report three cases of multiple infarcted regenerative nodules in
      liver cirrhosis after gastrointestinal hemorrhage.

PMID- 18815463
TI  - [Hepatocellular carcinoma with lymphoid stroma: report of two cases].
AB  - We report two cases of hepatocellular carcinoma with prominent lymphocytic
      infiltration, which has been described as a subtype of hepatocellular carcinoma
      with good prognosis. One case showed lymphoid follicles and dense lymphocytic
      infiltrates within the tumor and its periphery, and the other case showed marked
      lymphocytic infiltration in the cancerous tissue. Piecemeal necrosis of cancer
      cells and atypical reactive changes were evident. The two cases were seronegative
      for hepatitis B surface antigen, antibody to hepatitis C virus, and Epstein-Barr
      virus DNA. One of the cases showed Clonorchis infestation. The prognostic
      significance of lymphocytic stroma in hepatocellular carcinoma requires further
      investigation.

PMID- 18815464
TI  - [Epithelioid hemangioendothelioma of the liver].

PMID- 18815465
TI  - [Imaging findings of hepatic adenoma].

PMID- 18815467
TI  - From the editor-in-chief; it's time to recognize good things.
AB  - It's time to celebrate some of the very good things that are happening for
      nursing and for nurses.

PMID- 18815468
TI  - What else does the box say?
AB  - Have you ever thought about why - if you do - you read the combination of
      ingredients found in a particular product? Usually, you want to know what makes
      something good for you or not; what enhances the palatability of the chosen item;
      or, sometimes, it's sheer curiosity as to whether you have made a good choice.
      More often than not, you buy something by virtue of its popularity and market
      penetration or its personal appeal. The successful launch of a product is
      frequently linked to creative and targeted marketing. But let's face it, there
      are times when we throw caution to the wind and simply ignore the caloric,
      saturated fat, sodium and sugar counts of a chosen product. In so doing, we
      accept the associated potential risks to our well-being.

PMID- 18815469
TI  - Reorganizing nursing work on surgical units: a time-and-motion study.
AB  - A time-and-motion study was conducted in response to perceptions that the
      surgical nursing staff at a Montreal hospital was spending an excessive amount of
      time on non-nursing care. A sample of 30 nurse shifts was observed by trained
      observers who timed nurses' activities for their entire working shift using a
      hand-held Personal Digital Assistant. Activities were grouped into four main
      categories: direct patient care, indirect patient care, non-nursing and personal
      activities. Break and meal times were excluded from the denominator of total
      worked hours. A total of 201 working hours were observed, an average of 6 hours,
      42 minutes per nurse shift. The mean proportions of each nurse shift spent on the
      main activity categories were: direct care 32.8%, indirect care 55.7%, non
      nursing tasks 9.0% and personal 2.5%. Three activities (communication among
      health professionals, medication verification/preparation and documentation)
      comprised 78.9% of indirect care time. Greater time on indirect care was
      associated with work on night shifts and on the short-stay surgical unit.
      Subsequent work reorganization focused on reducing time spent on communication
      and medications. The authors conclude that time-and-motion studies are a useful
      method of monitoring appropriate use of nursing staff, and may provide results
      that assist in restructuring nursing tasks.

PMID- 18815470
TI  - "I'm a different kind of nurse": advice from nurses in rural and remote Canada.
AB  - The sustainability of the rural and remote nursing workforce in Canada is
      increasingly at issue as the country becomes more urbanized and the nursing
      workforce ages. In order to support the retention of nurses in rural and remote
      communities and the recruitment of nurses to these communities, we require a
      better understanding of what is important to rural and remote nurses themselves.
      As part of the in-depth interviews conducted within The Nature of Nursing
      Practice in Rural and Remote Canada, a national research project, registered
      nurses (RNs) were asked what advice they would have for new nurses, educators,
      administrators and policy makers. This is the first of two papers describing that
      advice. It focuses on RNs in acute care, long-term care, home care, community
      health/public health and primary care roles in rural and remote communities
      across the country. The RNs were generous with their advice and gave many rich
      examples. While they were enthusiastic about their nursing practice and
      encouraging of other nurses to work in rural settings, they were intent that
      improvements be made in several key areas: education available to new
      practitioners and themselves, working conditions for rural and remote nurses,
      leadership, organizational supports and policies that better support rural and
      remote practice and communities.

PMID- 18815471
TI  - "There's rural, and then there's rural": advice from nurses providing primary
      healthcare in northern remote communities.
AB  - Nursing practice in remote northern communities is highly complex, with unique
      challenges created by isolation, geography and cultural dynamics. This paper, the
      second of two focusing on the advice offered by nurses interviewed in the
      national study, The Nature of Nursing Practice in Rural and Remote Canada,
      considers suggestions from outpost nurses. Their advice to new nurses was: know
      what you are getting into; consider whether your personal qualities are suited
      for northern practice; learn to listen and listen to learn; expect a steep
      learning curve, even if you are experienced; and take action to prevent burnout.
      Recommendations for educators were to offer programs that prepare nurses for the
      realities of outpost nursing and provide opportunities for accessible, flexible,
      relevant continuing education. The outpost nurses in this study counselled
      administrators to stay in contact with and listen to the perspectives of nurses
      at the "grassroots," and not merely to fill positions but instead to recruit
      outpost nurses effectively and remunerate them fairly. The study findings
      highlighted the multiple interrelated strategies that nurses, educators and
      administrators can use to optimize practice in remote northern communities.

PMID- 18815472
TI  - Developing leadership in nurse managers: the British Columbia Nursing Leadership
      Institute.
AB  - The British Columbia Nursing Administrative Leadership Institute for First Line
      Nurse Leaders (BC NLI) is a collaborative partnership among British Columbia's
      Chief Nursing Officers, the Ministry of Health Nursing Directorate and the
      University of British Columbia School of Nursing. This initiative consists of a
      four-day residential program and a year-long leadership project between BC NLI
      participants and their organizational mentors. The evidence-based curriculum
      covers universal leadership and management concepts, but it also addresses
      leadership issues of relevance to nurse leaders in today's complex healthcare
      environments. The BC NLI is part of a provincial health human resources endeavour
      to ensure sufficient nursing leaders - for now and in the future. This paper will
      discuss the development, implementation and evaluation of the BC NLI. Unique
      aspects of the program, such as its online networking component, will be
      described, and its role in nursing leadership research will be briefly examined.

PMID- 18815473
TI  - Decision rationale for common problems. Foreword.

PMID- 18815474
TI  - Renal replacement therapy in the critical care unit.
AB  - Acute renal failure is common in critically ill patients. Many intensive care
      unit patients require renal replacement therapy (RRT). Hemodialysis can be
      performed as intermittent treatments or as continuous RRT, which can be
      customized to clinical goals by the use of carefully designed replacement fluids
      and hemodialysates. The available forms of RRT are reviewed, with emphasis on the
      clinical indications that contribute to the choice and design of therapy.
      Practical issues and troubleshooting are discussed, as are available options for
      anticoagulation during RRT. Consideration is given to modality choice,
      hemodynamic issues, costs, and physiologic outcomes.

PMID- 18815475
TI  - Gastrointestinal prophylaxis in critically ill patients.
AB  - Physiologic stress associated with illness and hospitalization is known to result
      in gastrointestinal ulceration, especially among the critically ill. The
      complication of this stress-related mucosal disease could be prevented with
      appropriate application of pharmacologic prophylaxis. Vigilance by the nursing
      staff is required to properly detect and manage the condition.

PMID- 18815476
TI  - Prevention of nosocomial infections in the intensive care unit.
AB  - Infections are considered nosocomial if they occur 48 hours or more after
      hospital admission or within 30 days after discharge. One third of these
      infections are considered preventable. Many studies have shown that with proper
      education and use of strict guidelines, we can prevent nosocomial infections in
      the intensive care unit. In this article, we will review the literature on
      preventing catheter-associated urinary tract infection, central line-associated
      blood stream infection, and ventilator-associated pneumonia.

PMID- 18815477
TI  - Sleep in the intensive care unit setting.
AB  - Sleep is essential to human life. Sleep patterns are significantly disrupted in
      patients who are hospitalized, particularly those in the intensive care unit.
      Sleep deprivation is pervasive in this patient population and impacts health and
      recovery from illness. Immune system dysfunction, impaired wound healing, and
      changes in behavior are all observed in patients who are sleep deprived. Various
      factors including anxiety, fear, and pain are responsible for the sleep
      deprivation. Noise, light exposure, and frequent awakenings from caregivers also
      add to these effects. Underlying medical illnesses and medications can also
      dramatically affect a patient's ability to sleep efficiently. Therapy with
      attempts to minimize sleep disruption should be integrated among all of the
      caregivers. Minimization of analgesics and other medications known to adversely
      affect sleep should also be ensured. Although further research in the area of
      sleep deprivation in the intensive care unit setting needs to be conducted,
      effective protocols can be developed to minimize sleep deprivation in these
      settings.

PMID- 18815479
TI  - Chronic obstructive pulmonary disease and cytokines.
AB  - Chronic obstructive pulmonary disease is a leading cause of morbidity and
      mortality. Understanding what happens at a cellular level will lead to more
      effective treatments. Interleukins and transforming growth factor-beta are
      important inflammatory mediators that may be significant in the evolution of
      chronic obstructive pulmonary disease.

PMID- 18815480
TI  - Aspirin for the primary prevention of adverse cardiovascular events.
AB  - There is consideration controversy regarding the use of aspirin for the
      prophylaxis of certain cardiovascular conditions, such as coronary thrombosis and
      stroke. An exploration of current literature suggests that the decision to adopt
      a routine aspirin regimen must follow a careful analysis of potential risks as
      well as benefits. Nurses share a vital role in patient education related to
      aspirin regimens, to guard against potential complications of low-dose aspirin
      therapy, including gastrointestinal bleeding and stroke.

PMID- 18815481
TI  - An exploratory examination of medical gas booms versus traditional headwalls in
      intensive care unit design.
AB  - Should power, medical gases, and monitoring and communications systems be located
      in a headwall or a ceiling-mounted boom in intensive care unit (ICU) rooms?
      Often, only the financial costs could be determined for the options, whereas data
      regarding its potential influence on teamwork, safety, and efficiency are
      lacking. Hence, purchase decisions are more arbitrary than evidence based. This
      study simulated care delivery in settings with a traditional headwall and a
      ceiling boom. Observed were the way the following elements were managed and the
      extent either system affected flexibility, ergonomics, and teamwork: tubing for
      intravenous fluids, medical gases, and suction drainage; monitoring leads and
      equipment power cords; and the medical equipment itself. Simulation runs
      involving 6 scenarios were conducted with the voluntary participation of 2
      physicians, 2 nurse practitioners, 2 respiratory therapists, and 4 registered
      nurses at a children's tertiary care center in December 2007. Analysis suggests
      that booms have an advantage over headwalls in case of high-acuity ICU patients
      and when procedures are performed inside patient rooms. However, in case of lower
      acuity ICU patients, as well as when procedures are not typically conducted in
      the patient room, booms may not provide a proportionate level of advantage when
      compared with the additional cost involved in its procurement.

PMID- 18815484
TI  - Emerging technology, physical activity, and sedentary behavior.

PMID- 18815485
TI  - The evolving definition of "sedentary".
AB  - Studies that did not directly measure sedentary behavior often have been used to
      draw conclusions about the health effects of sedentariness. Future claims about
      the effects of sedentary, light, and moderate-to-vigorous activities on health
      outcomes should be supported by data from studies in which all levels of physical
      activity are differentiated clearly and measured independently.

PMID- 18815486
TI  - Does AMP-activated protein kinase negatively mediate aged fast-twitch skeletal
      muscle mass?
AB  - The activity of 5'-adenosine monophosphate (AMP)-activated protein kinase (AMPK),
      a negative regulator of cell size, is up-regulated with age in resting and
      overloaded fast-twitch skeletal muscle but not slow-twitch muscle. Here, we
      provide evidence to support the hypothesis that elevated AMPK activity plays a
      potentially important integrative role in the age-related atrophy and diminished
      capacity for growth specific to fast-twitch skeletal muscle.

PMID- 18815487
TI  - Nhlh2: a basic helix-loop-helix transcription factor controlling physical
      activity.
AB  - In mice, targeted deletion of the basic helix-loop-helix transcription factor,
      nescient helix-loop-helix 2 (Nhlh2), leads to adult-onset obesity and reduced
      physical activity. We propose the novel hypothesis that transcriptional activity
      by Nhlh2 (NHLH2 in humans) controls either the ability or the motivation for
      exercise.

PMID- 18815488
TI  - Muscle fascicle and tendon behavior during human locomotion revisited.
AB  - High-speed ultrasonography has revealed that, in human locomotion, the nature of
      fascicle and tendon length changes varies depending on the task, contraction
      intensity, and the muscles involved. The findings emphasize that the active
      fascicles of the gastrocnemius muscle are suddenly stretched, although they are
      shortening. This short-lasting stretch triggers the stretch reflex, timing of
      which is dependent on running speed.

PMID- 18815489
TI  - The structure of variability in human walking and running is speed-dependent.
AB  - The variability of gait in human walking and running is not random but shows self
      similarity that is dependent on the speed of locomotion. The strength of the long
      range correlations for each gait pattern follows a U-shaped function that is
      centered on the respective preferred speed of locomotion.

PMID- 18815490
TI  - Exploring the mechanism of skilled overarm throwing.
AB  - Although the kinematics and dynamics of overarm throws, such as baseball
      pitching, have been studied extensively, the relations between these measures
      remain largely unknown. This review uses a three-dimensional analysis to
      characterize the mechanical basis of skilled overarm throws by focusing on how
      each joint angular acceleration is produced by the muscle torques, gravity
      torques, and velocity-dependent torques.

PMID- 18815491
TI  - "Self-sustainable" gym clubs tackling obesity: "exercise" for "energy".

PMID- 18815493
TI  - Does the physician's emotional intelligence matter? Impacts of the physician's
      emotional intelligence on the trust, patient-physician relationship, and
      satisfaction.
AB  - BACKGROUND: Much of the literature pertinent to management indicates that service
      providers with high emotional intelligence (EI) receive higher customer
      satisfaction scores. Previous studies offer limited evidence regarding the impact
      of physician's EI on patient-physician relationship. PURPOSES: Using a multilevel
      and multisource data approach, the current study aimed to build a model that
      demonstrated the impact of a physician's EI on the patient's trust and the
      patient-physician relationship. METHODOLOGY: The survey sample included 983
      outpatients and 39 physicians representing 11 specialties. FINDINGS: Results of
      path analyses demonstrated that the ratio of patient's follow-up visits (p < .01)
      and the nurse-rated EI for physicians (p < .05) had positive effects on the
      patient's trust. The impact of patient's trust on patient's satisfaction was
      mediated by the patient-physician relationship at a significant level (p < .01).
      The patient-physician relationship had a significantly positive effect on
      patient's satisfaction (p < .001). The model accounted for 37% of the variance of
      patient's trust, 67% of the PDR, and 58% of patient's satisfaction on physician
      services. PRACTICE IMPLICATIONS: This study suggests that nurses had the
      sensitivity and intellectual skills in assessing the physician's performance and
      the patient's need. Our findings suggest that patient's trust is the cornerstone
      of the patient-physician relationship; however, mutual trust and professional
      respect between nurses and physicians play a critical role in reinforcing the
      patient-physician relationship to effect improvements in the provision of patient
      centered care.

PMID- 18815494
TI  - Clinician- and organization-level factors in the adoption of evidence-based care
      for depression in primary care.
AB  - BACKGROUND AND PURPOSE: Although more individuals are receiving care for
      depression than those in the past, they often do not receive high-quality care.
      Strategies to improve quality have focused on changing clinician behavior and
      more recently on reducing practice barriers. Both strategies hold promise but
      have had widely varying success either because practices have not successfully
      removed barriers or because removing barriers alone is not sufficient for
      improving care. It is unknown under which circumstances clinicians with a high
      propensity toward recognizing depression and providing depression care can
      overcome barriers. We explore organizational and clinician factors affecting
      patient receipt of guideline-concordant services. METHODOLOGY/APPROACH: We use
      data from adult patients with major depression receiving care in a geographically
      diverse group of primary care practices participating in the Quality Improvement
      for Depression study. We estimate the effects of barriers and clinician
      propensity on six aspects of depression care and adequate treatment. FINDINGS:
      Barriers and propensity interact in affecting depression services. In comparison
      with similar clinicians in practices with few barriers, high-propensity
      clinicians working in practices with more barriers are less likely to provide
      depression education and are likely to provide fewer follow-up calls and fewer
      follow-up visits. High-propensity clinicians are more likely to offer
      antidepressants in practices with more barriers. PRACTICE IMPLICATIONS: To
      improve the quality of care, efforts should both eliminate practice barriers and
      increase clinician propensity to provide care. Future research on factors
      associated with quality improvement can benefit from an approach which specifies
      how organizational and clinician factors interact to enact change.

PMID- 18815495
TI  - Consensus guidelines: improving the delivery of clinical preventive services.
AB  - BACKGROUND: Medical directors from the largest competing health plans in the
      state came together in a noncompetitive way to collaborate on improving the
      delivery of clinical preventive service (CPS) among their provider base. They
      identified one consistent set of CPS guidelines based on U.S. Preventive Services
      Task Force recommendations, the health plan consensus guidelines (HPCG), that
      they could endorse as priority for guideline implementation. PURPOSE: The
      purposes of this study were to assess clinicians' knowledge and use of CPS
      recommendations as a guide to delivering preventive care services to their
      patients and, most importantly, to test the effectiveness of providing the HPCG
      to clinicians in an effort to increase knowledge and use of CPS guidelines.
      DESIGN: Within-subjects repeated-measures design was used. We hypothesized an
      increase in clinician's knowledge and use of CPS after the provision of the HPCG.
      METHODS: Survey methodology, including two surveys that assessed clinicians'
      knowledge and use of CPS in practice, was used. Health plan clinician databases
      were obtained from the health plans that participated in the development of the
      HPCG. Health plan clinicians directly involved in delivering preventive services
      were invited to participate in the study. Final sample included 163 clinicians.
      Spearman's rho correlation coefficients were determined to examine the
      relationships between clinician's knowledge and clinician's use of CPS
      guidelines. Differences between knowledge and use of CPS before and after HPCG
      were examined by t tests. FINDINGS: No difference was found in the familiarity
      with U.S. Preventive Services Task Force guidelines before and after receipt of
      HPCG. However, clinician's use increased significantly. PRACTICE IMPLICATIONS: A
      consistent set of CPS guidelines provided by competing health plans can improve
      the delivery of CPS among contracted health plan clinicians. This approach
      provides a template for competing health plans nationwide to come to consensus on
      guidelines that support clinicians in the delivery of CPS ().

PMID- 18815496
TI  - Structural and process factors affecting the implementation of antimicrobial
      resistance prevention and control strategies in U.S. hospitals.
AB  - BACKGROUND: To address increases in the incidence of infection with antimicrobial
      resistant pathogens, the National Foundation for Infectious Diseases and Centers
      for Disease Control and Prevention proposed two sets of strategies to (a)
      optimize antibiotic use and (b) prevent the spread of antimicrobial resistance
      and control transmission. However, little is known about the implementation of
      these strategies. PURPOSE: Our objective is to explore organizational structural
      and process factors that facilitate the implementation of National Foundation for
      Infectious Diseases/Centers for Disease Control and Prevention strategies in U.S.
      hospitals. METHODS: We surveyed 448 infection control professionals from a
      national sample of hospitals. Clinically anchored in the Donabedian model that
      defines quality in terms of structural and process factors, with the structural
      domain further informed by a contingency approach, we modeled the degree to which
      National Foundation for Infectious Diseases and Centers for Disease Control and
      Prevention strategies were implemented as a function of formalization and
      standardization of protocols, centralization of decision-making hierarchy,
      information technology capabilities, culture, communication mechanisms, and
      interdepartmental coordination, controlling for hospital characteristics.
      FINDINGS: Formalization, standardization, centralization, institutional culture,
      provider-management communication, and information technology use were associated
      with optimal antibiotic use and enhanced implementation of strategies that
      prevent and control antimicrobial resistance spread (all p < .001). However,
      interdepartmental coordination for patient care was inversely related with
      antibiotic use in contrast to antimicrobial resistance spread prevention and
      control (p < .0001). IMPLICATIONS: Formalization and standardization may
      eliminate staff role conflict, whereas centralized authority may minimize
      ambiguity. Culture and communication likely promote internal trust, whereas
      information technology use helps integrate and support these organizational
      processes. These findings suggest concrete strategies for evaluating current
      capabilities to implement effective practices and foster and sustain a culture of
      patient safety.

PMID- 18815497
TI  - Hospital ethical climate and teamwork in acute care: the moderating role of
      leaders.
AB  - BACKGROUND: Health care delivery teams have received much attention in recent
      years from researchers and practitioners. Recent empirical research has
      demonstrated that objective and subjective outcomes tend to be improved when care
      teams function smoothly and efficiently. However, little is known about how the
      work environment, or care context, influences team processes that lead to better
      outcomes. PURPOSE: The purposes of this study were to explore acute care staff's
      perceptions of how two components of the work environment, the ethical climate
      and continuous quality improvement leadership, influence teamwork and to begin to
      identify actionable approaches for improving teamwork. Although ethical climate
      influences have been studied in several sectors, research is lacking in health
      care. METHODOLOGY/APPROACH: A cross-sectional field study explored how the
      ethical climate impacted teamwork in an acute care setting and how continuous
      quality improvement leadership behaviors moderated the relationship between the
      ethical climate and teamwork. FINDINGS: Results indicated that clinicians who
      perceived the ethical climate to be benevolent were significantly more likely to
      say that teamwork was better. Furthermore, we found that continuous quality
      improvement leadership styles moderated the relationship between the ethical
      climate and teamwork. PRACTICE IMPLICATIONS: Although a benevolent ethical
      climate appears to be associated with effective teamwork, it appears that the
      proximate continuous quality improvement behaviors exhibited by leaders have a
      significant impact as well, above and beyond the climate. Implications for
      research and practice are discussed.

PMID- 18815498
TI  - The impact of charismatic leadership on followers' initiative-oriented behavior:
      a study in German hospitals.
AB  - BACKGROUND: Organizations in the health care sector are undergoing extensive
      structural reforms. To face these challenges, management initiatives that foster
      employees' commitment to and support for organizational change are needed in
      hospitals. PURPOSES: In literature, a charismatic leadership style has proved to
      be especially helpful in times of crisis and change as well as an essential
      antecedent of followers' discretionary behavior in organizations. Thus, the aim
      of the study was to investigate charismatic leadership as a means to enhance
      followers' initiative-oriented behavior in hospitals. In the hospital context,
      two situational conditions have to be taken into account. We hypothesized that
      both employees' job autonomy and stress in the workplace will moderate the
      positive relationship between charismatic leadership and followers' initiative
      oriented behavior. METHODOLOGY/APPROACH: We investigated 543 members of medical
      staff (physicians and nurses) in six German hospitals by using a questionnaire.
      The hypotheses were tested by conducting hierarchical regression analyses and
      interpreting main effects and interactions effects. FINDINGS: Charismatic
      leadership significantly predicted followers' initiative-oriented behavior.
      Moreover, our study confirmed the moderating effect of job autonomy. However, the
      moderating effect of followers' stress was not confirmed by our data. PRACTICE
      IMPLICATIONS: First, the results of our investigation point at the positive
      impact that charismatic leaders have on followers' initiative-oriented behavior
      in the hospital. Several studies have shown that training can improve leaders'
      abilities in charismatic leadership. Thus, a suggestion for supervisor
      development from this is not only to provide professional training but also to
      intensify efforts in training specialized on charismatic leadership. Second, to
      support followers' participation in change processes, hospital managers should
      consider if and how the degree of followers' job autonomy can be enhanced.

PMID- 18815499
TI  - Testing the hospital value proposition: an empirical analysis of efficiency and
      quality.
AB  - PURPOSES: To assess the relationship between hospitals' X-inefficiency levels and
      overall care quality based on the National Quality Forum's 27 safe practices
      score and to improve the analytic strategy for assessing X-inefficiency.
      METHODOLOGY: The 2005 versions of the American Hospital Association and Leapfrog
      Group's annual surveys were the basis of the study. Additional case mix indices
      and market variables were drawn from the Centers for Medicare and Medicaid
      Services data sources and the Area Resource File. Data envelopment analysis was
      used to determine hospitals' X-inefficiency scores relative to their market-level
      competitors. Regression was used to assess the relationship between X
      inefficiency and quality, controlling for organizational and market
      characteristics. Expenses (total and labor expenditures), case-mix-adjusted
      admissions, length of stay, and licensed beds defined the X-inefficiency
      function. The overall National Quality Forum's safe practice score, health
      maintenance organization penetration, market share, and teaching status served as
      independent control variables in the regression. FINDINGS: The National Quality
      Forum's safe practice scores are significantly and positively correlated to
      hospital X-inefficiency levels (beta = .105, p < or = .05). The analysis of the
      value proposition had very good explanatory power (adjusted R(2) = .414; p < or =
      .001; df = 7, 265). Contrary to earlier findings, health maintenance organization
      penetration and being a teaching hospital were positively related to X
      inefficiency. Similar with others' findings, greater market share and for-profit
      ownership were negatively associated with X-inefficiency. PRACTICE IMPLICATIONS:
      Measurement of overall hospital quality is improving but can still be made
      better. Nevertheless, the National Quality Forum's measure is significantly
      related to efficiency and could be used to create differential pay-for
      performance programs. A market-segmented analytic strategy for studying
      hospitals' efficiency yields results with a high degree of explanatory power.

PMID- 18815500
TI  - Searching for a business case for quality in Medicaid managed care.
AB  - BACKGROUND: Despite the prevalence of evidence-based interventions to improve
      quality in health care systems, there is a paucity of documented evidence of a
      financial return on investment (ROI) for these interventions from the perspective
      of the investing entity. PURPOSES: To report on a demonstration project designed
      to measure the business case for selected quality interventions in high-risk high
      cost patient populations in 10 Medicaid managed care organizations across the
      United States. METHODOLOGY/APPROACH: Using claims and enrollment data gathered
      over a 3-year period and data on the costs of designing, implementing, and
      operating the interventions, ROIs were computed for 11 discrete evidence-based
      quality-enhancing interventions. FINDINGS: A complex case management program to
      treat adults with multiple comorbidities achieved the largest ROI of 12.21:1.
      This was followed by an ROI of 6.35:1 for a program which treated children with
      asthma with a history of high emergency room (ER) use and/or inpatient admissions
      for their disease. An intervention for high-risk pregnant mothers produced a
      1.26:1 ROI, and a program for adult patients with diabetes resulted in a 1.16:1
      return. The remaining seven interventions failed to show positive returns,
      although four sites came close to realizing sufficient savings to offset
      investment costs. PRACTICE IMPLICATIONS: Evidence-based interventions designed to
      improve the quality of patient care may have the best opportunity to yield a
      positive financial return if it is focused on high-risk high-cost populations and
      conditions associated with avoidable emergency and inpatient utilization.
      Developing the necessary tracking systems for the claims and financial
      investments is critical to perform accurate financial ROI analyses.

PMID- 18815501
TI  - Factors influencing physician use of clinical electronic information technologies
      after adoption by their medical group practices.
AB  - BACKGROUND: A major factor limiting efficiency and quality gains from clinical
      information technologies is the lack of full use by the clinicians. PURPOSE: To
      identify the practice and physician characteristics that influence the use of e
      scripts after adoption. METHODS: Data were obtained from 27 primary care medical
      group practices that had e-script technology for 2 years. Physician and practice
      characteristics were obtained from the clinics, and the proportion of each
      physician's prescriptions sent electronically was calculated from the
      prescription records. Practice culture data were obtained from a survey of the
      physicians in each practice. Data were analyzed using hierarchal regression.
      FINDINGS: Practice-level variables explain most of the variance in the use of e
      scripts by physicians, although there are significant differences in use among
      specialties as well. General internists have slightly lower use rates and
      pediatricians have the highest rates. Larger practices and multispecialty
      practices have higher use rates, and five practice culture dimensions influence
      these rates; two have a negative influence and three (organizational trust,
      adaptive, and a business orientation) have a positive influence. PRACTICE
      IMPLICATIONS: While previous studies have identified physician characteristics
      and product deficiencies as factors limiting the use of electronic information
      technologies in medical practices, our data indicate that the influence of these
      factors may be highly dependent on the culture of the practice. Consequently,
      practice administrators can improve physician acceptance and use of these
      technologies by making sure that there is a culture/technology fit before
      deciding on a product.

PMID- 18815503
TI  - The interdisciplinary team.

PMID- 18815504
TI  - Collaboration between neuropsychologists and speech-language pathologists in
      rehabilitation settings.
AB  - OBJECTIVE: The purpose of this study was to understand the barriers and
      facilitators of communication and collaboration between speech-language
      pathologists (SLPs) and neuropsychologists (NPs) in rehabilitation settings.
      METHOD: Focus groups were held at 3 rehabilitation hospitals. Participants were a
      convenience sample and were considered representatives of acquired brain injury
      rehabilitation teams that include SLPs and NPs. There were a total of 28 SLPs and
      10 NPs in the sample. The study used a semistructured interview guide for the
      focus group discussions, using questions centered on major areas known to be
      related to interdisciplinary collaboration. Written notes and audio recordings
      were analyzed for recurring and strongly stated themes. RESULTS: Consistent
      themes emerged across focus groups, which included (1) structure of
      collaboration, (2) perceived roles of NPs and SLPs in assessment and
      intervention, (3) similarities and differences in training and philosophic
      perspectives, (4) barriers to successful collaboration, and (5) facilitators of
      collaboration. CONCLUSION: The SLPs and NPs valued the contributions of both
      professions in the management of patients with acquired brain injuries. Effective
      collaboration appeared to be influenced by several factors and is discussed. It
      was evident that effective communication was a key and powerful element in
      successful collaboration.

PMID- 18815505
TI  - Preliminary evaluation of the Cognitive and Linguistic Scale: a measure to assess
      recovery in inpatient rehabilitation following pediatric brain injury.
AB  - OBJECTIVE: A preliminary investigation of the psychometric properties of the
      Cognitive and Linguistic Scale (CALS), a measure of cognitive and linguistic
      recovery following brain injury in children and adolescents. PARTICIPANTS: One
      hundred children and adolescents (aged 2-19 years) with acquired or traumatic
      brain injury were included. METHODS: The CALS was administered at inpatient
      rehabilitation admission and discharge. RESULTS: Internal consistency and
      interrater reliability were high. Factor analysis revealed 2 factors (basic
      responding, higher-level cognitive skills). Correlations with the Functional
      Independence Measure for Children (WeeFIM) ranged from 0.51 to 0.89; highest
      correlation was between WeeFIM cognitive domain and CALS total score. CALS scores
      improved significantly between admission and discharge. CONCLUSION: On the basis
      of these preliminary analyses, the CALS is a promising measure to track cognitive
      and linguistic recovery in children and adolescents with brain injury during
      inpatient rehabilitation.

PMID- 18815506
TI  - Long-term outcome after severe traumatic brain injury: the McGill
      interdisciplinary prospective study.
AB  - OBJECTIVE: To obtain a comprehensive understanding of long-term outcome after
      severe traumatic brain injury (sTBI). PARTICIPANTS: Forty-six patients with sTBI.
      DESIGN: Comparison of interdisciplinary evaluation results at discharge from
      acute care and at 2 to 5 year follow-up. MAIN MEASURES: Extended Glasgow Outcome
      Scale, the FIM instrument, and the Neurobehavioral Rating Scale-Revised. RESULTS:
      Significant improvement was observed on the FIM instrument, the Extended Glasgow
      Outcome Scale, and on 3 factors of the Neurobehavioral Rating Scale-Revised.
      These measures at discharge were significant predictors of outcome. CONCLUSION:
      Patients with sTBI 2 to 5 years postinjury showed relatively good physical and
      functional outcome but poorer cognitive and emotional outcome.

PMID- 18815507
TI  - Behavior management on an acute brain injury unit: evaluating the effectiveness
      of an interdisciplinary training program.
AB  - OBJECTIVE: To measure the effect of behavior management training on restraint use
      and prn medication delivery on an acute inpatient brain injury unit.
      SETTING/PARTICIPANTS: Interdisciplinary staff and hospitalized brain injury
      patients on a 20-bed unit within a freestanding rehabilitation hospital.
      INTERVENTION: Staff participated in the Nonviolent Crisis Intervention (NCI)
      program from the Crisis Prevention Institute. MAIN OUTCOME MEASURES: Applied
      physical restraints and delivered prn medications. RESULTS: Despite comparable
      patient levels of agitation severity across the duration of the study, the use of
      physical restraints initially declined and then increased after training. Data
      collected on prn medication delivery also indicated a trend for an increase in
      the delivery of select medication categories across time. CONCLUSION: NCI
      training resulted in a temporary, short-lived reduction in physical restraint
      use, but had an inverse effect on prn medication delivery for select categories
      of medication. Medication delivery significantly increased over time and
      restraint use eventually exceeded baseline level. Ramifications of these results
      are discussed.

PMID- 18815508
TI  - Benefits of categorization training in patients with traumatic brain injury
      during post-acute rehabilitation: additional evidence from a randomized
      controlled trial.
AB  - BACKGROUND: Preliminary research with the Categorization Program (CP) indicated
      that this therapeutic modality is beneficial in improving cognitive abilities in
      survivors of moderate-to-severe traumatic brain injury (TBI). This study provides
      additional evidence for the use of the CP in postacute TBI cognitive
      rehabilitation. METHODS: Twenty-one participants in the experimental group
      received the CP training, and 14 participants in the control group received the
      conventional treatment used at their rehabilitation center. Following
      neuropsychological testing, participants began their therapy program. RESULTS:
      There was no significant difference in the baseline performance of the 2 TBI
      groups on any of the measures. CP-dependent measures correlated significantly
      with several neuropsychological tests. Both groups improved in their
      neuropsychological test performance and on functional outcomes tests. However,
      subjects in the experimental group improved on more tests than participants in
      the control group. Posttest performance of subjects in the TBI control group was
      significantly lower on the CP Test 1 and CP Test 2 as compared with the
      experimental group. Furthermore, the performance of participants in the CP group
      improved across the 3 probe tasks demonstrating generalizability to new tasks;
      the performance of participants in the control group did not improve.
      CONCLUSIONS: The CP is an effective therapy method to reduce categorization
      impairment and improve cognitive performance of survivors of TBI who are enrolled
      in postacute rehabilitation. This study contributes to the growing body of
      evidence supporting cognitive rehabilitation efforts after TBI.

PMID- 18815509
TI  - Evaluation of an interdisciplinary team intervention to improve therapeutic
      alliance in post-acute brain injury rehabilitation.
AB  - OBJECTIVE: Evaluate an intervention to improve an alliance between an
      interdisciplinary team and clients with traumatic brain injury attending post
      acute brain injury rehabilitation. DESIGN: Prospective design, 2 consecutive
      samples-historical control (CNT) and treatment (TX). METHODS: Sample of 104
      clients (69 CNT, 35 TX) admitted to post-acute brain injury rehabilitation
      completed admit/discharge questionnaires. RESULTS: The TX group had higher
      functional status at discharge than the CNT group. Stronger team alliance was
      associated with program completion, return to productivity, stronger client
      alliance, less family discord, and fewer depressive symptoms. CONCLUSIONS:
      Findings provide direction for a larger study examining the effectiveness of this
      intervention to improve outcome after traumatic brain injury.

PMID- 18815516
TI  - The role of citizenship, employment, and socioeconomic characteristics in health
      insurance coverage among Asian subgroups in the United States.
AB  - BACKGROUND: Asians are the third largest and one of the fastest growing minority
      groups in the United States. OBJECTIVE: We present health insurance data for the
      6 largest national subgroups: Chinese, Filipino, Indian, Korean, Vietnamese, and
      Japanese. We also contrast the characteristics that result in differences in
      coverage, including the role of citizenship. RESEARCH DESIGN: Cross-sectional
      analysis of data from the 2006 Current Population Survey. MEASURES: We used
      responses to questions on nativity and parental nativity to categorize Asian
      respondents into subgroups. SUBJECTS: The 2006 CPS sampled 8918 Asians including
      1923 Chinese, 2210 Filipino, 1302 Indian, 951 Korean, 903 Vietnamese, and 808
      Japanese. RESULTS: Koreans had the highest proportion lacking coverage at 29.8%,
      followed by Vietnamese at 21.5% and Chinese at 16.8%. Indians, Filipinos, and
      Japanese had rates of coverage similar to or better than non-Hispanics whites
      (NHWs). The proportion of US-born Chinese with employer coverage (65%) was
      similar to NHWs, but only 50% of Chinese noncitizens had employer coverage and
      27% of these were uninsured. Among Koreans and Vietnamese, noncitizens were most
      vulnerable, with 41% and 31%, respectively, being uninsured. In contrast, 70% of
      noncitizen Indian had employer coverage and only 15% were uninsured. Gaps in
      coverage among Koreans and Vietnamese were largely due to employment in service
      industry and blue collar occupations as well as small firms, which are less
      likely to provide coverage. CONCLUSIONS: The current system of employer coverage
      is not succeeding in covering Asian groups equitably. Distinct initiatives to
      expand health coverage would have variable effects on these diverse subgroups.

PMID- 18815517
TI  - Introduction to special theme issue on health insurance in the United States.

PMID- 18815518
TI  - Thinking clearly about the issue of health insurance.

PMID- 18815519
TI  - Separate and unequal: self-segregation in health insurance.

PMID- 18815520
TI  - Access, primary care, and the medical home: rights of passage.

PMID- 18815521
TI  - To preserve and strengthen Medicare.

PMID- 18815522
TI  - The Veterans Health Administration in the context of health insurance reform.

PMID- 18815523
TI  - The causal effect of health insurance on utilization and outcomes in adults: a
      systematic review of US studies.
AB  - BACKGROUND: No current consensus exists on the causal effect of gaining or losing
      health insurance on health care utilization and health outcomes. OBJECTIVE: To
      systemically search and review available evidence of estimated causal effects of
      health insurance on health care utilization and/or health outcomes among
      nonelderly adults in the United States. RESEARCH DESIGN: A systematic search of 3
      electronic databases (PubMed, JSTOR, EconLit) was performed. To be included in
      the review, studies had to have a publication date after 1991; a population of
      nonelderly adults; analyses comparing an uninsured group to an appropriate
      control group; and 1 of 3 study designs that account for potential reverse
      causality and provide estimates of causal effects (longitudinal cohort,
      instrumental variable analysis, or quasi-experimental design). RESULTS: A total
      of 9701 studies, including duplicates, were primarily screened. Fourteen studies
      fulfilled the criteria to be included in this review-4 longitudinal cohort
      studies using standard regression or fixed effects analysis, 5 longitudinal
      cohort studies using instrumental variable regression analysis, and 5 quasi
      experimental studies. CONCLUSIONS: Results of our review of empirical studies
      that estimate causal relationships between health insurance and health care
      utilization and/or health outcomes consistently show that health insurance
      increases utilization and improves health. Specifically, health insurance had
      substantial effects on the use of physician services, preventive services, self
      reported health status, and mortality conditional on injury and disease. These
      results both confirm and contradict comparable results from the RAND Health
      Insurance Experiment, the gold standard on relationships between health
      insurance, utilization, and health.

PMID- 18815524
TI  - Effect of premium, copayments, and health status on the choice of health plans.
AB  - OBJECTIVE: Explore effects of comorbidity and prior health care utilization on
      choice of employee health plans with different levels of cost sharing. DATA
      SOURCES/STUDY SETTING: Mayo Clinic employees in Rochester, Minnesota (MCR) under
      age 65 in January 2004; N = 20,379. STUDY DESIGN: Assessment of a natural
      experiment where self-funded medical care benefit options were changed to contain
      costs within a large medical group practice. Before the change, most employees
      were enrolled in a plan with first dollar coverage, while 18% had a plan with
      copays and deductibles. In 2004, 3 existing plans were replaced by 2 new options,
      one with lower premiums and higher out-of-pocket costs and the other with higher
      premiums, a lower coinsurance rate, and lower out-of-pocket maximums. DATA
      COLLECTION/EXTRACTION METHODS: Data on employees were merged across insurance
      claims, medical records, eligibility files, and employment files for 2003 and
      2004. PRINCIPAL FINDINGS: As the number of chronic comorbidities among family
      members increased, the probability of choosing high-premium option also
      increased. Seventy-two percent of employees with at least 1 family member with
      comorbidity chose the high-cost option versus 54.7% of employees with no
      comorbidities. High-premium and low-premium plans seem to subdivide population
      into discrete risk categories, which may adversely affect the future stability of
      the insurance plan options. CONCLUSIONS: Various factors affect decision making
      of employees regarding the choice of plan with different levels of cost-sharing.
      In a natural experiment setting where all options were redesigned, the health
      status of employees and their dependents played a very significant role in plan
      choice.

PMID- 18815525
TI  - A usual source of care: supplement or substitute for health insurance among low
      income children?
AB  - OBJECTIVES: To examine the separate and combined effects of having health
      insurance and a usual source of care (USC) on access to healthcare for low-income
      children and to determine if one or the other is superior in ensuring better
      access to necessary services. METHODS: We conducted cross-sectional,
      multivariable analyses of data from a mail-return survey of Oregon's food stamp
      program. Results from 2681 completed surveys were weighted back to a population
      of 84,087 families with adjustments for oversampling techniques and nonresponse.
      RESULTS: Among low-income Oregon children, those with health insurance and a USC
      reported the best access to healthcare. In multivariable comparisons to this
      reference group, insured children without a USC had higher rates of unmet medical
      need [odds ratio (OR) = 2.18; 95% confidence interval (CI): 1.27-3.73]; no doctor
      visits in 12 months (OR = 6.77; 95% CI: 3.80-12.06); and problems obtaining
      specialty care (OR = 4.12; 95% CI: 1.59-10.68). Similarly, having a USC but not
      health insurance was associated with an even higher likelihood of unmet medical
      needs (OR = 4.33; 95% CI: 2.85-6.57); as well as unmet prescription needs (OR =
      2.64, 95% CI: 1.77-3.94), and problems obtaining dental care (OR = 4.83; 95% CI:
      3.31-7.06). CONCLUSIONS: Incremental policy solutions are being proposed that
      focus on either health insurance coverage for children or expanded access to
      primary care. However, neither approach displaces the need for the other. The
      effects of a USC and health insurance, together, are additive predictors of the
      likelihood that children have optimal access to necessary healthcare services.

PMID- 18815526
TI  - Medicaid re-enrollment policies and children's risk of hospitalizations for
      ambulatory care sensitive conditions.
AB  - BACKGROUND: Many poor children rotate through the Medicaid program with periods
      of being uninsured. OBJECTIVE: To determine health and cost consequences of a
      Medicaid policy change that extended the Medicaid eligibility redetermination
      period for children in California from 3 to 12 months. RESEARCH DESIGN: A
      pre/postevaluation with a comparison group of a natural experiment. SUBJECTS: All
      California children ages 1-17 years who received a minimum of 1 month of Medicaid
      coverage in 1999-2000 (3,288,171) and/or 2001-2002 (3,230,120). MEASURES: The
      percentage of children with continuous Medicaid coverage and the hospitalization
      rate and costs for ambulatory care sensitive conditions in each time period.
      RESULTS: In the 2 years before the policy change, 49% of children had continuous
      Medicaid coverage compared with 62% in the 2 years afterward (P < 0.0001). After
      adjusting for demographic and programmatic differences in the population of
      children in each time period, the relative hazard of a hospitalization for an
      ambulatory care sensitive condition for a child with at least 1 month of Medicaid
      coverage decreased to 0.74 (P < 0.0001) after the extension of the Medicaid
      enrollment period. There was dollars 17 million less in estimated hospitalization
      costs for ambulatory care sensitive conditions with less frequent eligibility
      redetermination that partially offset the estimated dollars 150 million in
      additional costs to Medicaid for providing more continuous coverage. CONCLUSIONS:
      Reducing the frequency of eligibility redetermination for children in Medicaid
      was associated with higher costs to the program but more continuity of insurance
      coverage, improvements in health, and lower hospital spending.

PMID- 18815527
TI  - Switching health insurance and its effects on access to physician services.
AB  - BACKGROUND: This study examines the factors associated with discontinuous health
      insurance coverage without periods of uninsurance during the past year (ie,
      switching coverage), and whether it has a detrimental effect on basic access to
      care. RESEARCH DESIGN: We analyze the 2003 California Health Interview Survey
      samples of adults, ages 19-64 (n = 32,850) and children, ages 0-18 (n = 13,062),
      using weighted bivariate and multivariate analyses. We stratified the population
      first by age (modeling adults separately from children) and then by health status
      (modeling the full population and the population reporting fair or poor health
      separately). RESULTS: Income, race/ethnicity, age, gender, and rural status were
      significant factors associated with switching coverage. Adults who switched
      insurance had significantly reduced odds of having a usual source of care [odds
      ratio (OR) = 0.63, P < 0.001)] compared with those with continuous coverage. In
      addition, adults and children who switched coverage were significantly more
      likely to report delaying care because of cost or insurance issues (adults: OR =
      1.65, P < 0.001; children: OR = 2.00, P < 0.001). Children in fair or poor health
      who switched insurance coverage had much higher odds of reporting a delay in care
      (OR = 5.48, P < 0.001). CONCLUSIONS: Children and adults had disruptions in their
      basic access to health care when they experienced discontinuous insurance. These
      findings highlight the advantages of retention of enrollees as one means of
      promoting access to health care, in the short term, and the benefit of a
      continuous national health insurance program in the long term.

PMID- 18815528
TI  - Does public insurance provide better financial protection against rising health
      care costs for families of children with special health care needs?
AB  - BACKGROUND: Health care costs grew rapidly since 2001, generating substantial
      economic pressures on families, especially those with children with special
      health care needs (CSHCN). OBJECTIVE: To examine how the growth of health care
      costs affected financial burden for families of CSHCN between 2001 and 2004 and
      to determine the extent to which health insurance coverage protected families of
      CSHCN against financial burden. RESEARCH DESIGN AND SUBJECTS: In 2001-2004, 5196
      families of CSHCN were surveyed by the national Medical Expenditure Panel Survey
      (MEPS). MEASURES: The main outcome was financial burden, defined as the
      proportion of family income spent on out-of-pocket (OOP) health care expenditures
      for all family members, including OOP costs and premiums. Family insurance
      coverage was classified as: (1) all members publicly insured, (2) all members
      privately insured, (3) all members uninsured, (4) partial coverage, and (5) a mix
      of public and private with no uninsured periods. RESULTS: An upward trend in
      financial burden for families of CSHCN occurred and was associated with growth of
      economy-wide health care costs. A multivariate analysis indicated that, given the
      economy-wide increase in medical costs between 2001 and 2004, a family with CSHCN
      was at increased risk in 2004 for having financial burden exceeding 10% of family
      income [odds ratio (OR) = 1.39; P < 0.01]. Similar findings were noted for
      financial burden exceeding 20% of family income. Over 15% of families with public
      insurance had financial burden exceeding 10% of family income compared with 20%
      of families with private insurance (P < 0.05; chi2 test). After controlling for
      covariates, publicly-insured families of CSHCN had significantly lower likelihood
      of financial burden of >10% or 20% of family income than privately-insured
      families. CONCLUSIONS: Rising health care costs increased financial burden on
      families of CSHCN in 2001-2004. Public insurance coverage provided better
      financial protection than private insurance against the rapidly rising health
      care costs for families of CSHCN.

PMID- 18815529
TI  - The State Children's Health Insurance Program (SCHIP) and prepregnancy coverage
      of teenage mothers.
AB  - BACKGROUND: The 1997 State Children's Health Insurance Program (SCHIP) program
      allowed states to expand Medicaid to uninsured children through age 18 in
      families under 200% of the federal poverty level. Prepregnancy insurance coverage
      of adolescents may help reduce unintended pregnancies, address other medical
      issues, and allow for early and adequate prenatal care for those carrying to
      term. OBJECTIVES: We tested the effects of SCHIP implementation on insurance
      coverage for teenage mothers and investigated whether these effects varied by
      type of state SCHIP program--Medicaid expansion, stand-alone program, or some
      combination of these. RESEARCH DESIGN: We used Pregnancy Risk Assessment
      Monitoring System data from 1996 through 2000 and difference-in-differences
      analysis to analyze coverage changes for teenage mothers (age <20) relative to
      those for mothers aged 20-24 years old, a group whose Medicaid eligibility was
      not affected by SCHIP policies. POPULATION STUDIED: Our raw sample of teenage and
      older mothers in Alaska, Oklahoma, South Carolina, Florida, Maine, New York, and
      West Virginia equaled 23,171 (811,638 weighted). RESULTS: SCHIP implementation
      was associated with an almost 10 percentage point increase in prepregnancy
      coverage among teens under age 17. Although there were increases in both public
      and private coverage only the latter was statistically significant. The only
      statistically significant increase in Medicaid coverage, equal to almost 16
      percentage points, was among 18-year-olds in states with Medicaid expansion
      programs. CONCLUSIONS: The temporary extension of SCHIP allows time to consider
      how to maintain the program's potentially positive effect on the reproductive
      health of adolescents.

PMID- 18815530
TI  - Racial disparities in Medicaid enrollment and prenatal care initiation among
      pregnant teens in Florida: comparisons between 1995 and 2001.
AB  - BACKGROUND: Teens and racial and ethnic minority women are less likely to
      initiate prenatal care (PNC) in the first trimester of pregnancy than their
      counterparts. OBJECTIVE: This study examines the impact of Medicaid program
      changes in the late 1990s on the timing of Medicaid enrollment and PNC initiation
      among pregnant teens by race and ethnicity. RESEARCH DESIGN: Using Medicaid
      enrollment and claims data and a difference-in-differences method, we examine how
      the patterns of prepregnancy Medicaid enrollment, PNC initiation, and racial and
      ethnic disparities in PNC changed over time after controlling for person- and
      county-level characteristics. SUBJECTS: We included 14,089 teens in Florida with
      a Medicaid-covered delivery in fiscal years 1995 and 2001. MEASURES: Prepregnancy
      enrollment was defined as enrollment 9 or more months before delivery; late or no
      PNC was defined as initiation of PNC within 3 months of delivery or not at all.
      RESULTS: For teens enrolled in traditional welfare-related categories, the
      proportion with prepregnancy Medicaid enrollment increased and the proportion
      with late or no PNC declined from 1995 to 2001. Teens enrolled under the Omnibus
      Budget Reconciliation Act (OBRA) expansion category in 2001 were less likely than
      welfare-related teen enrollees to have prepregnancy coverage but were more likely
      to initiate PNC early. Racial disparities were found in PNC initiation among the
      1995 welfare-related group and the 2001 expansion group but were eliminated or
      greatly reduced among the 2001 welfare-related group. CONCLUSIONS: Providing
      public insurance coverage improves access to care but is not sufficient to meet
      Healthy People 2010 goals or eliminate racial and ethnic disparities in PNC
      initiation.

PMID- 18815531
TI  - Hispanics and health insurance coverage: the rising disparity.
AB  - BACKGROUND: Many reports have focused attention on the rising percentage of
      adults in the United States without health insurance. This hides the fact that
      the uninsured rate for non-Hispanic nonelderly adults has held fairly steady
      since 1983, while the rate for Hispanics has increased. OBJECTIVES: To document
      the trends in the coverage rate by source of coverage for different population
      groups between 1983 and 2003 and suggest how changes in the composition of these
      groups have contributed to these trends. RESEARCH DESIGN: We stack panels of the
      Survey of Income and Program Participation to create a nationally representative
      20-year pooled cross-section of nonelderly adults. We calculate actual trends in
      insurance coverage as well as 2 hypothetical time series that disentangle the
      effect of the decreasing coverage rate for Hispanics from the growth of the
      Hispanic adult population. RESULTS: Although the increase in uninsured rate is
      largest for Hispanic noncitizens, US-born Hispanics also have a significant
      upward trend, primarily driven by a decrease in private coverage, with little
      change in public coverage. Although the increase in the Hispanic population
      contributed to the increase in the number of uninsured adults, the widening
      coverage disparity was more important. CONCLUSIONS: Hispanic nonelderly adults,
      both US-born and immigrants, have fallen behind non-Hispanic nonelderly adults in
      insurance coverage. Although combinations of economic growth and private and
      public insurance policy changes have maintained, and in some cases improved,
      overall coverage rates for non-Hispanics, these changes have not helped Hispanic
      adults, leading to increased disparities in coverage.

PMID- 18815532
TI  - Minding the gap: a decomposition of emergency department use by Medicaid
      enrollees and the uninsured.
AB  - OBJECTIVE: To examine differences in Emergency Department (ED) utilization
      between Medicaid enrollees and the uninsured. DATA AND METHODS: We use nationally
      representative data for adults age 19-64 from the 2004 Medical Expenditure Panel
      Survey. We calculate descriptive statistics highlighting differences in
      distributions of measurable characteristics and logit regressions describing
      differences in the coefficients of the characteristics between the 2 groups.
      Blinder-Oaxaca nonlinear decomposition methods are applied to quantify the effect
      that differences in measurable characteristics between the groups have on the
      differences in ED utilization, as well as examine the magnitude of the effect on
      utilization of differences in behavior between the groups. RESULTS: Twenty-seven
      percent of Medicaid enrollees had an ED visit, whereas 10% of those uninsured the
      entire year had an ED visit. Roughly half of the utilization gap can be explained
      by differences in measurable characteristics. Although predisposing factors such
      as demographic and socioeconomic characteristics explain little of the gap, the
      variables capturing health limitations reflecting need explain a more substantial
      amount of the gap. Specifically, the higher presence of chronic conditions
      reported by Medicaid enrollees accounts for 18 percentage points of the gap, and
      reporting fair or poor health status explains 10 percentage points of the
      disparity. CONCLUSIONS: Decomposition analysis results show that differences in
      measurable characteristics between the groups explain half of the disparity in
      visits. The remaining portion of the gap in ED utilization is driven by
      differences in unmeasured or unobserved characteristics between the groups such
      as care-seeking behavioral differences.

PMID- 18815533
TI  - Comparison of cancer diagnosis and treatment in Medicare fee-for-service and
      managed care plans.
AB  - OBJECTIVE: To compare the Medicare managed care (MC) and fee-for-service (FFS)
      sectors on stage at diagnosis and treatment patterns for prostate, female breast,
      and colorectal cancers, and to examine patterns across MC plans. DATA:
      Surveillance, Epidemiology, and End Results-Medicare linked data. METHODS: Among
      cases diagnosed at ages 65-79 between 1998 and 2002, we selected all MC enrollees
      (n = 42,467) and beneficiaries in FFS (n = 82,998) who resided in the same
      counties. MC and FFS samples were compared using logistic regression, adjusting
      for demographic, geographic, and clinical covariates. RESULTS: The percentage of
      late stage cases was similar in MC and FFS for prostate and colorectal cancers;
      there were slightly fewer late stage breast cancer cases in MC after adjustment
      (7.3% vs. 8.5%, P < 0.001). Within MC, radical prostatectomy was performed less
      frequently for clinically localized prostate cancer (18.3% vs. 22.4%, P <
      0.0001), and 12 or more lymph nodes were examined less often for resected colon
      cancer cases (40.9% vs. 43.0%, P < 0.05). Treatment patterns for early stage
      breast cancer were similar in MC and FFS. Analyses of treatment patterns at the
      individual plan level revealed significant variation among plans, as well as
      within the FFS sector, for all 3 types of cancer. CONCLUSIONS: On average, there
      are few significant differences in cancer diagnosis and treatment between MC and
      FFS. Such comparisons, however, mask the wide variability among MC plans, as well
      as FFS providers. Observed variation in patterns of care may be related to
      patient selection, but can potentially lead to outcome differences. These
      findings support the need for quality measures to evaluate plan practices and
      performance.

PMID- 18815534
TI  - Effects of reaching the drug benefit threshold on Medicare members' healthcare
      utilization during the first year of Medicare Part D.
AB  - BACKGROUND: Information on the effects of reaching the Medicare Part D standard
      drug benefit threshold is limited. OBJECTIVES: Describe and compare pre- and post
      threshold healthcare and medication utilization of Medicare beneficiaries who
      reach threshold relative to those who do not reach threshold and those who do not
      have a threshold. RESEARCH DESIGN: Retrospective study of 21,349 beneficiaries
      enrolled into a Medicare Direct Pay Plan with a standard threshold and 9088 Part
      D-eligible beneficiaries without a threshold. We used Poisson methods to compare
      utilization and conditional Poisson models to assess utilization changes.
      Medication adherence was determined. RESULTS: The 1237 (6%) beneficiaries who
      reached threshold were older, had greater morbidity, received more medications,
      and had more medical office visits (all P < 0.001) than beneficiaries who did not
      reach threshold. After adjustment, those who reached threshold had greater
      incidences of inpatient [risk ratio (IRR) = 1.85; 95% confidence interval (CI):
      1.64-2.09] and emergency department use (IRR = 1.60; 95% CI: 1.40-1.83). After
      reaching threshold, primary care visits decreased compared with the same time
      frame in 2005 for those who reached threshold (IRR = 0.86; 95% CI: 0.79-0.93) and
      a matched group with no threshold (IRR = 0.88; 95% CI: 0.84-0.92). Adherence to
      chronic medications declined over time in both groups, but adherence decline was
      greater for beneficiaries who reached threshold. CONCLUSIONS: Beneficiaries who
      reach threshold are older, have more morbidity, and use more medications.
      Although medication adherence declines after reaching threshold, its association
      with changes in other healthcare utilization is not clear.

PMID- 18815535
TI  - Back to third grade: a vision of health care for all.

PMID- 18815536
TI  - Chronic high-fat diets induce oxide injuries and fibrogenesis of pancreatic cells
      in rats.
AB  - OBJECTIVES: The mechanism of pancreatic damages induced by chronic high-fat diets
      (HFDs) remains unknown. The current study was to detect the involvement of free
      fatty acids (FFAs) and lipid peroxidation in pancreatic injuries in rats induced
      by a long-term HFD. METHODS: Rats of HFD groups (n = 12) were fed with an HFD for
      2, 4, 6, 10, and 18 weeks, respectively. Pancreatic malondialdehyde content and
      the concentration of FFA were measured. Histopathologic changes were observed by
      Sirius red staining for fibrosis and immunostaining of the pancreatic stellate
      cells for desmin, alpha-smooth muscle actin, platelet-derived growth factor
      receptor type beta, and transforming growth factor beta1. RESULTS: Pancreatic
      malondialdehyde content, the number of desmin and alpha-SMA positive cells
      significantly increased in all the HFD groups (P < 0.05). The levels of
      pancreatic FFA, platelet-derived growth factor receptor type beta, and
      transforming growth factor beta1 increased in rats of 2-, 4-, and 6-week HFD
      groups (P < 0.05). These enhancements were accompanied with sequential
      histopathology alterations that resulted from acute inflammatory response in the
      early stages of secondary pancreatic fibrosis. CONCLUSIONS: The results indicate
      that chronic HFD increased pancreatic FFA and lipid peroxidation associated with
      pancreatic injuries and collagen synthesis by activated pancreatic stellate cells
      in rats.

PMID- 18815537
TI  - Pdx-1-driven overexpression of aurora a kinase induces mild ductal dysplasia of
      pancreatic ducts near islets in transgenic mice.
AB  - OBJECTIVES: To further explore the oncogenic activity of Aurora A kinase while
      attempting to develop a useful mouse model for pancreatic cancer, Aurora A kinase
      was targeted to pancreatic duodenal homeobox gene-1 (Pdx-1)-positive cells.
      METHODS: Aurora A kinase overexpression was targeted to mouse pancreas tissues
      using the Pdx-1 promoter in a transgenic model. The pancreas tissues of 7- to 11
      month-old transgenic animals were evaluated for metastatic adenocarcinomas,
      preinvasive ductal neoplasia, or other histological anomalies. RESULTS:
      Examination of pancreatic tissue from Pdx-1-Aurora A transgenic mice revealed
      abnormalities, such as mild islet cell hyperplasia, lymphocytic infiltration, and
      general dysplasia between ductal/islet cell interfaces. However, most tissues
      from these transgenic mice were normal. CONCLUSIONS: The overexpression of Aurora
      A can potentially initiate the development of mild abnormalities in pancreatic
      tissue; however, neither preinvasive ductal neoplasia nor fully metastatic
      adenocarcinomas were observed. Combining the Pdx-1-Aurora A transgenic model with
      other genetic alterations may provide additional insight.

PMID- 18815538
TI  - Effect of celecoxib and the novel anti-cancer agent, dimethylamino-parthenolide,
      in a developmental model of pancreatic cancer.
AB  - OBJECTIVES: Cancer of the exocrine pancreas is the fourth leading cause of cancer
      related deaths in the United States. The efficacy of a novel bioavailable
      anticancer agent, dimethylamino-parthenolide (DMAPT), and the cyclooxygenase 2
      inhibitor, celecoxib, was evaluated in a carcinogen-induced developmental model
      of pancreatic cancer. METHODS: Syrian golden hamsters were injected with N
      nitrosobis(2-oxopropyl)amine, once weekly for 6 weeks. Upon the first injection,
      hamsters were randomized as follows: placebo, low-/high-dose DMAPT (20 and 40
      mg/kg per day), low-/high-dose celecoxib (10and 50 mg/kg per day), or combination
      DMAPT/celecoxib (low/low, high/high). RESULTS: The 32-week trial showed that 40
      mg/kg DMAPT alone significantly decreased the size of gross pancreatic cancers
      relative to placebo. No significant difference in gross tumor number was observed
      between the treatment groups and placebo with the exception of 50 mg/kg celecoxib
      with a higher tumor incidence; this group also exhibited lower lymphotactin
      levels suggestive of decreased immune surveillance. Tumor invasion into adjacent
      organs and metastasis were not observed in the DMAPT/celecoxib treatment groups.
      Drug targets including prostaglandin E2, prostaglandin E2 metabolite and
      activated nuclear factor kappaB were significantly decreased. CONCLUSIONS:
      Dimethylamino-parthenolide and celecoxib have the potential to be novel
      chemotherapeutic agents for pancreatic cancer; however, further optimization or
      the use of other modalities may be required for chemoprevention.

PMID- 18815539
TI  - Predictors of severity and survival in acute pancreatitis: validation of the
      efficacy of early warning scores.
AB  - OBJECTIVES: Early Warning Scores (EWS) is a widely used scoring system monitoring
      patient progress, which we have previously shown to predict outcome from acute
      pancreatitis. This study examined EWS from a larger group of patients to confirm
      if this predictive value held true. METHODS: The EWS scores were compared with
      the Acute Physiology and Chronic Health Evaluation II (APACHE II) scores,
      modified organ dysfunction scores, Imrie scores, computed tomography grading
      scores, and Ranson criteria for 181 admissions with acute pancreatitis. The
      accuracy of EWS in predicting outcome was determined by receiver operator
      characteristics. RESULTS: A total of 181 patients were identified with acute
      pancreatitis. On day 1 of admission, APACHE II scores were the most accurate
      predictor of mortality with an area under curve (AUC) values of 0.876, closely
      followed by EWS (AUC, 0.827). By day 2 and 3 after admission, the EWS was the
      most accurate predictor of mortality (AUC, 0.910 and 0.934, respectively). The
      APACHE II was the second most accurate scoring system at 48 and 72 hours (AUC,
      0.892 and 0.911, respectively). CONCLUSIONS: The EWSs on days 2 and 3 after
      admission are sensitive and specific in predicting mortality from acute
      pancreatitis. It is as accurate as the APACHE II scores and easier to implement
      in daily practice.

PMID- 18815540
TI  - Strategy for differentiating autoimmune pancreatitis from pancreatic cancer.
AB  - OBJECTIVES: It is of utmost importance that autoimmune pancreatitis (AIP) be
      differentiated from pancreatic cancer (PC) because some AIP cases undergo
      unnecessary laparotomy or pancreatic resection on suspicion of PC. This study
      aimed to develop an appropriate strategy for differentiating between AIP and PC.
      METHODS: Clinical, serological, and radiological features of 17 AIP patients
      forming a masslike lesion on pancreas head and 70 patients with pancreatic head
      cancer were compared. RESULTS: Numerous findings can be used to distinguish
      between AIP and PC, and the following are more likely in AIP: fluctuating
      jaundice; elevated serum IgG4 levels; delayed enhancement of the enlarged
      pancreas and a capsule-like low-density rim on computed tomography; long or
      skipped narrowed portion with side branches of the main pancreatic duct without
      upstream dilatation on endoscopic retrograde pancreatography, extrapancreatic
      lesions, such as stenosis of the intrahepatic bile duct, salivary gland swelling,
      and retroperitoneal mass; and responsiveness to steroid therapy. CONCLUSIONS: In
      elderly male patients presenting with obstructive jaundice and a pancreatic mass,
      AIP should be considered in the differential diagnosis. Based on a combination of
      clinical, serological, and radiological findings, AIP can be differentiated from
      PC. An algorithm for management of patients with a masslike lesion on pancreas
      head is presented.

PMID- 18815541
TI  - Higher islet amyloid load in men than in women with type 2 diabetes mellitus.
AB  - OBJECTIVES: Type 2 diabetes mellitus is characterized histopathologically by
      islet amyloid deposits formed from islet amyloid polypeptide. The aim of this
      study was to investigate sex difference in islet amyloid of type 2 diabetic
      patients. METHODS: Pancreas specimens were collected from 235 autopsies with type
      2 diabetes mellitus. Islet amyloid was identified with Congo red stain. The load
      of islet amyloid deposits was assessed by prevalence (percentage of cases with
      islet amyloid deposits), frequency (percentage of islets containing amyloid
      deposits), and severity (percentage of islet area occupied by amyloid deposits).
      RESULTS: Women (n = 80) and men (n = 155) had similar age of death, duration of
      diabetes, body mass index, and hemoglobin (Hb)A1c level. Islet amyloid was found
      in 30.0% of the women and in 44.5% of the men (P = 0.035). None of 9 women
      younger than 50 years had islet amyloid. Frequency of amyloid-affected islets was
      31.5% +/- 13.1% in women and 41.1% +/- 14.3% in men (P = 0.008). Severity of
      amyloid-affected islet area was 29.0% +/- 12.5% in women and 38.5% +/- 14.6% in
      men (P = 0.007). CONCLUSIONS: Sex is a determinant of the development of islet
      amyloid in type 2 diabetes mellitus. This sex difference in islet amyloid may be
      related to a potential benefit of female sex hormones.

PMID- 18815542
TI  - Study of the protective effects of dexamethasone on ileum mucosa injury in rats
      with severe acute pancreatitis.
AB  - OBJECTIVES: To study the protecting effects of dexamethasone on ileum mucosa
      injury of rats with severe acute pancreatitis (SAP). METHODS: The SAP rats were
      prepared by improved Aho's methods. The plasma endotoxin and inflammatory
      mediators in serum were determined. The rat mortality, pathological changes of
      terminal ileum, nuclear factor kappa B (NF-kappaB), apoptotic indexes, and
      apoptotic related protein expression were observed. RESULTS: The plasma
      endotoxin, inflammatory mediators, and NF-kappaB protein expression as well as
      pathological scores of the treatment group of ileum mucosa were lower than those
      of the model group at different time points. P selectin in model group
      significantly exceeded the dexamethasone treatment group at 3 and 6 hours (P <
      0.01, P < 0.05). Caspase-3 protein expression in dexamethasone treatment group
      significantly exceeded the model group at 3 and 6 hours (P < 0.05), and apoptotic
      indexes were higher than those of the model group at 6 hours (P < 0.05), but Bax
      protein has shown no marked difference among groups. CONCLUSIONS: Dexamethasone
      can reduce the endotoxin level and inflammatory mediators and down-regulate NF
      kappaB protein expression of ileum mucosa, and ileum mucosa epithelial cell
      apoptosis induction was involved as well. The tissue microarrays technique is of
      advantage in SAP study.

PMID- 18815543
TI  - Prophylactic octreotide administration does not prevent post-endoscopic
      retrograde cholangiopancreatography pancreatitis: a meta-analysis of randomized
      controlled trials.
AB  - There is no consensus whether octreotide can prevent post-endoscopic retrograde
      cholangiopancreatography (ERCP) pancreatitis. We performed a meta-analysis
      comparing octreotide with placebo in randomized controlled trials. METHODS: :
      Electronic databases, including MEDLINE, EMBASE, Cochrane controlled trials
      register, the Cochrane Library, and the Science Citation Index updated to January
      2007, were searched to retrieve relevant randomized controlled trials. Outcome
      measures were post-ERCP pancreatitis. RESULTS: : Fifteen trials were identified,
      and statistical homogeneity was present among these selected trials. After all
      the trials were pooled, post-ERCP pancreatitis occurred in 7.0% of controls (92
      of 1320) versus 5.5% of treated patients (72 of 1301), without statistical
      significance (odds ratio, 0.78; 95% confidence interval, 0.57-1.08). Subsequent
      sensitivity analyses and subgroup analyses also produced no significant effect.
      Only in large-scale trials (>200 cases) that octreotide could statistically,
      significantly prevent pancreatitis (odds ratio, 0.50; 95% confidence interval,
      0.32-0.79). CONCLUSIONS: : On the basis of current best evidence, octreotide
      cannot prevent post-ERCP pancreatitis.

PMID- 18815544
TI  - Meta-analysis of prophylactic allopurinol use in post-endoscopic retrograde
      cholangiopancreatography pancreatitis.
AB  - The aim of this study was to evaluate the effectiveness and the safety of
      allopurinol in the prophylaxis of post-endoscopic retrograde
      cholangiopancreatography (ERCP) pancreatitis. METHODS: : We used the method
      recommended by the Cochrane Collaboration to perform a meta-analysis of
      randomized controlled trials (RCTs) of allopurinol in the prevention of post-ERCP
      pancreatitis (PEP), including 6 RCTs conducted all over the world. RESULTS: : Six
      RCTs totaling 1554 patients undergoing ERCP were included. When the RCTs were
      analyzed, odds ratios of allopurinol were 0.74 (95% confidence interval [CI],
      0.37-1.48; P = 0.40) for PEP, 0.87 (95% CI, 0.33-2.28; P = 0.78) for severe PEP,
      0.88 (95% CI, 0.37-2.11; P = 0.78) for post-ERCP hyperamylasemia, and 0.19 (95%
      CI, 0.01-3.91; P = 0.28) for case-fatality ratio of PEP, thus indicating no
      beneficial effects of allopurinol on acute pancreatitis, PEP death rate, and
      hyperamylasemia. No evidence of publication bias was found. CONCLUSIONS: :
      Allopurinol cannot prevent the pancreatic injury after ERCP. Allopurinol is not
      recommended in the prophylaxis of PEP.

PMID- 18815545
TI  - Cystic neoplasms of the exocrine pancreas: an update of a nationwide survey in
      Korea.
AB  - OBJECTIVE: The purpose of this study was to update a previous study of cystic
      neoplasms of the pancreas (PCNs) conducted in Korea by the authors. METHODS:
      Clinicopathologic data and factors associated with malignancy were evaluated from
      PCNs originating from the exocrine pancreas diagnosed between January 1993 and
      June 2005 in 30 university hospitals throughout Korea. RESULTS: A total of 1064
      pathologically confirmed PCNs, which consisted of the following diagnoses, were
      collected: intraductal papillary mucinous neoplasm (IPMN), 436; mucinous cystic
      neoplasm (MCN), 268; solid pseudopapillary neoplasm (SPN), 195; serous cystic
      neoplasm (SCN), 162; acinar cell cystic neoplasm 2; and mature teratoma, 1. No
      malignant SCNs were diagnosed. In IPMN, advanced age, pancreatic head
      involvement, and hyperbilirubinemia were associated with malignancy based on
      multivariate analysis. In MCN, pancreatic head involvement was associated with
      malignancy based on multivariate analysis. CONCLUSIONS: Intraductal papillary
      mucinous neoplasms were the most common PCN observed in Korea. Solid
      pseudopapillary neoplasms were observed more frequently than those in studies
      from western countries. In IPMNs, advanced age was associated with malignancy,
      suggesting an adenoma-carcinoma sequence. Involvement of the pancreatic head was
      associated with malignancy in both IPMNs and MCNs, possibly warranting prompt
      surgical interventions.

PMID- 18815546
TI  - Ultrasonographic imaging of bile duct lesions in autoimmune pancreatitis.
AB  - OBJECTIVES: Patients with autoimmune pancreatitis (AIP) commonly have lesions in
      the bile duct itself and show stenosis of the bile duct system; however, no
      detailed study has evaluated the ultrasonographic findings of bile duct lesions
      in AIP. In this study, we monitored the clinical course and imaging findings,
      mainly ultrasonographic, of bile duct lesions in AIP. METHODS: We retrospectively
      analyzed the incidence of bile duct lesions, imaging findings, and clinical
      course in 37 patients with AIP. RESULTS: Characteristic bile duct and gallbladder
      wall thickening was recognized on ultrasound in 37.8% (14/37) of AIP patients. We
      divided the patients into 2 types according to the ultrasonographic findings of
      bile duct wall thickening: (1) 3-layer type (64.3%) and (2) parenchymal-echo type
      (35.7%). All 14 cases were treated with prednisolone, with immediate resolution
      of the bile duct lesions. CONCLUSION: Sclerosing cholangitis is one of the
      extrapancreatic lesions that are commonly detected in AIP patients; it is
      detected on ultrasonographic imaging as characteristic wall thickening. Our
      ultrasonographic findings reflect the fact that bile duct wall thickening in AIP
      is an inflammatory process that responds to prednisolone therapy. Ultrasonography
      is a useful tool in detecting biliary tract lesions in AIP.

PMID- 18815547
TI  - Resectable pancreatic adenocarcinoma: depiction of tumoral margins at contrast
      enhanced ultrasonography.
AB  - To evaluate if contrast-enhanced ultrasonography (CEUS) improves the depiction of
      tumoral margins of pancreatic adenocarcinoma in relation to tumor enhancement,
      using pathology as criterion standard. METHODS: Two hundred forty-one patients
      affected by pancreatic ductal adenocarcinoma were investigated at CEUS with a
      second-generation contrast medium of sulfur-hexafluoride microbubbles. Sixty
      seven (27.8%) of 241 tumors were resected. By consensus, 2 radiologists reviewed
      the CEUS examination results of the 67 tumors judging the enhancement as low
      (hypovascular lesions, hypoechoic tothe adjacent parenchyma) or high (iso- or
      hypervascular lesions, iso- or hyperechoic to the adjacent parenchyma). The
      resected tumors were evaluated at pathology for the presence of positive
      neoplastic (R+) or negative neoplastic (R-) resected margins. RESULTS: Of the 67
      resected tumors, 35 (52.3%) were R-, whereas 32 (47.7%) were R+. Moreover, at
      CEUS, of the 67 resected tumors, 43 (64.1%) were hypovascular with low
      enhancement and 24 (35.8%) were iso-hypervascular with high enhancement. In the R
      group, 27 (77.1%) of 35 tumors were hypovascular. In the R+ group, 16 (50%) of
      32 lesions were hypovascular. CONCLUSIONS: At CEUS the depiction of tumoral
      margins of pancreatic adenocarcinoma is more accurate in low enhancement than in
      high enhancement. The pattern of enhancement of pancreatic adenocarcinoma
      influences the depiction of tumoral margins at CEUS.

PMID- 18815548
TI  - Serum CA19-9 decline compared to radiographic response as a surrogate for
      clinical outcomes in patients with metastatic pancreatic cancer receiving
      chemotherapy.
AB  - OBJECTIVE: Serum carbohydrate antigen 19-9 (CA19-9) has never been compared to
      radiographic objective response as a surrogate for clinical outcomes in patients
      receiving chemotherapy for metastatic pancreatic cancer. METHODS: We compared
      CA19-9 decline to objective response as surrogate end points for both time to
      progression (TTP) and overall survival (OS) in patients with metastatic
      pancreatic cancer receiving fixed-dose rate gemcitabine. RESULTS: A total of 75
      patients from 2 studies were eligible for analysis. Significant correlations were
      observed between maximum CA19-9 decline and both TTP (P < 0.0001) and OS (P <
      0.0001). Median OS was 12.2 months for patients with more than a 75% decline in
      CA19-9, 7.5 months for those with 0% to 75% decline, and 3.5 months for those
      with no decline. Correlations between best radiographic response and both TTP (P
      < 0.0001) and OS (P=0.0013) were also observed. Median OS was 12.8 months for
      patients with partial or complete response, 8.0 months for those with stable
      disease, and 4.6 months for those with progressive disease. CONCLUSIONS: CA19-9
      decline compares favorably with objective response as a strong predictor of TTP
      and OS. CA19-9 could represent amore cost-effective tool for the evaluation of
      new therapies and guidance of clinical management in patients with metastatic
      pancreatic cancer.

PMID- 18815549
TI  - Specific expression of endoglin (CD105) in endothelial cells of intratumoral
      blood and lymphatic vessels in pancreatic cancer.
AB  - Endoglin, a component of the transforming growth factor beta receptor expressed
      in embryonic vascular endothelial cells, is expressed in vascular endothelial
      cells in several types of cancer tissues and is involved in tumor angiogenesis.
      The aim of this study was to analyze the expression pattern of endoglin in
      pancreatic cancer and assess the involvement of this molecule in cancer
      progression. METHODS: Pancreatic cancer and adjacent normal tissues obtained from
      36 patients were subjected to immunostaining with anti-endoglin antibody, and the
      microvessel density (MVD) was assessed based on the number of endoglin-positive
      vessels. RESULTS: Endoglin was expressed in endothelial cells of small capillary
      like vessels in pancreatic cancer tissues from all 36 patients, and lymphatic
      endothelial cells in the tumors also expressed endoglin. In contrast, endothelial
      cells of vascular and lymphatic vessels in normal pancreatic tissue did not
      express endoglin. Patients with a higher MVD of endoglin-positive vessels had
      shorter disease-free and overall survival. CONCLUSIONS: Endoglin is specifically
      expressed in endothelial cells of small vascular and lymphatic vessels in cancer
      tissues. The MVD of endoglin-positive vessels may also be a useful prognostic
      marker in pancreatic cancer patients.

PMID- 18815550
TI  - Islet auto transplantation following total pancreatectomy: a long-term assessment
      of graft function.
AB  - Total pancreatectomy is considered the final resort in the treatment of chronic
      pancreatitis; however, here we show that simultaneous islet autotransplantation
      can abrogate the onset of diabetes. METHODS: : In Leicester, 46 patients have now
      undergone total pancreatectomy with immediate islet auto transplant, and they
      have received a median of 2246 islet equivalent (IEQ)/kg body weight (range, 405
      20,385 IEQ/kg body weight). RESULTS: : Twelve patients have shown periods of
      insulin independence, for a median of 16.5 months (range, 2-63 months), and 5
      remain insulin independent. Over the 10 years of follow-up, there has been a
      notable increase in insulin requirement per kilogram per day, and percentage of
      glycosylated hemoglobin levels have increased significantly (r = 0.66, P = 0.01).
      However, 100% of patients tested were C-peptide positive at their most recent
      assessment, and high fasting and stimulated C-peptide values recorded at 10 years
      after transplantation, 1.44 (range, 1.09-1.8 ng/mL) and 2.86 ng/mL (range, 1.19
      4.53 ng/mL), respectively, suggest significant graft function in the long term.
      In addition, median serum creatinine has increased very little after the
      operation (71 nmol/L [range, 49-125 nmol/L] atpreoperation vs 76.5 nmol/L [range
      72-81 nmol/L] at year 10), suggesting no diabetic nephropathy. CONCLUSIONS: :
      Although there is a notable decline in islet function after islet auto
      transplant, there is still evidence of significant long-term insulin secretion
      and possible protection against diabetic complications.

PMID- 18815551
TI  - Long-term nicotine exposure causes increased concentrations of trypsinogens and
      amylase in pancreatic extracts in the rat.
AB  - To develop radioimmunoassays (RIAs) for rat trypsinogens 1 and 2 and to
      investigate the effect of nicotine exposure on concentration and production of
      pancreatic zymogens in the rat. METHODS: Male Sprague-Dawley rats were supplied
      with either normal or nicotine-containing (0.77 mM) water for 28 days and were
      then killed. Rabbit antibodies for the activation peptides of trypsinogens 1 and
      2 were obtained for use in the RIAs. Concentrations of the both trypsinogens in
      pancreatic extracts were measured by the RIAs after activation by enterokinase.
      DNA and amylase were measured using commercial kits. mRNA for trypsinogens 1 and
      2, procolipase, and cholecystokinin receptor was measured by in situ
      hybridization. RESULTS: The specificity of the RIA for the trypsinogen 1
      activation peptide was satisfactory. The RIA for the trypsinogen 2 activation
      peptide showed a limited cross-reaction toward the synthetic trypsinogen 1
      activation peptide, but the importance of this cross-reaction was moderate when
      investigated in samples of activated trypsinogens. Weight gain was reduced in
      nicotine-treated animals. Concentrations of amylase, trypsinogen 1, trypsinogen
      2, and the ratio of trypsinogen 2 to 1 were all increased in pancreatic extracts
      of nicotine-fed animals. Total DNA and mRNA for the trypsinogens, procolipase,
      and cholecystokinin receptor were not affected by nicotine exposure. CONCLUSIONS:
      The combination of increased proenzyme concentrations and unaffected mRNA levels
      suggests that nicotine impairs secretion rather than production of pancreatic
      zymogens.

PMID- 18815552
TI  - Cytokine genotypes in acute pancreatitis: association with etiology, severity,
      and cytokine levels in blood.
AB  - The circumstances that determine how acute pancreatitis (AP) becomes severe are
      unknown. Differences in cytokine genetic encoding may determine the severity or
      influence the etiology of AP. This article investigates the relationship between
      different polymorphisms of tumor necrosis factor alpha (TNF-alpha), interleukin 1
      (IL-1), IL-1 receptor antagonist, IL-6, and IL-10 with the severity and etiology
      of AP and the serum levels of the cytokine encoded. METHODS: Patients with AP
      were included prospectively. Severity of the disease was determined according to
      Atlanta classification. Serum levels of these cytokines were determined within
      the first 72 hours after the onset of symptoms. The following polymorphisms were
      determined by polymerase chain reaction: IL-1a -889, IL-1b +3954, IL-1b -511,
      variable number tandem repeats, IL-6 -174, IL-6 -597, IL-10 -592, TNF-alpha 308,
      TNF-alpha 238, and TNF-B250. RESULTS: Eighty-four patients were included. The GA
      genotype of the TNF-alpha 238 polymorphism was associated with more frequent
      respiratory failure and shock than the GG genotype. Gallstone pancreatitis was
      associated with the CC genotype of the IL-6 -174 CC polymorphism. CONCLUSIONS: AG
      genotype of the TNF-alpha 238 polymorphism is associated with organic failure in
      patients with AP. The CC genotype of the IL-6 174 polymorphism is associated with
      biliary etiology of acute pancreatitis.

PMID- 18815553
TI  - Dual effect of ATP on glucose-induced insulin secretion in HIT-T15 cells.
AB  - OBJECTIVES: : The study investigated the dual effect of purinergic nucleotides on
      the secretion of insulin from pancreatic beta cells. METHODS: : The level of
      insulin secretion in HIT-T15 cells of static incubation was measured using a
      radioimmunoassay. RESULTS: : The adenine nucleotides reduced the level of glucose
      induced insulin secretion in a concentration-dependent manner, and the relative
      potency order (IC50; muM) was BzATP (6.9) > ATP (20.4) >/= alpha, beta-methylene
      ATP (23.3) >/= 2-methylthio-ATP (24.9). Suramin and PPADS (200 muM), which are
      blockers of the purinergic receptors, had a little influence on the activity of
      ATP. However, the inhibitory effect of ATP was reversed by preincubation with
      oxidized ATP (200 muM), which is a P2X7 antagonist. The level of insulin
      secretion in these preincubated cells exposed to the purinergic nucleotides
      increased in the following order: ATP > alpha, beta-methylene ATP >/= 2
      methylthio-ATP. A pretreatment with foskolin and PDBu (100 nM) potentiated the
      increasing effect of ATP on insulin secretion. The Western blotting showed the
      expression of P2X7 and P2Y11 receptors. CONCLUSIONS: : Purinergic stimulation has
      inhibitory activity on glucose-dependent insulin secretion through the activation
      of the P2X7 receptor, whereas it has enhancing effect through the activation of
      the P2Y11 receptor in HIT-T15 cells.

PMID- 18815554
TI  - Involvement of phosphatidylinositol-3 kinase/AKT/PKCzeta/lambda pathway in the
      effect of palmitate on glucose-induced insulin secretion.
AB  - OBJECTIVES: In the present study, a novel pathway by which palmitate potentiates
      glucose-induced insulin secretion by pancreatic beta cells was investigated.
      METHODS: Groups of freshly isolated islets were incubated in 10 mM glucose with
      palmitate, LY294002, wortmannin, and fumonisin B1 for measurement of insulin
      secretion by radioimmunoassay (RIA). Also, phosphorylation and content of AKT and
      PKC proteins were evaluated by immunoblotting. RESULTS: Glucose plus palmitate
      and glucose plus LY294002 or wortmannin (PI3K inhibitors) increased glucose
      induced insulin secretion by isolated pancreatic islets. Glucose at 10 mM induced
      AKT and PKCzeta/lambda phosphorylation. Palmitate (0.1 mM) abolished glucose
      stimulation of AKT and PKCzeta/lambda phosphorylation possibly through PI3K
      inhibition because both LY294002 (50 microM) and wortmannin (100 nM) caused the
      same effect. The inhibitory effect of palmitate on glucose-induced AKT and
      PKCzeta/lambda phosphorylation and the stimulatory effect of palmitate on glucose
      induced insulin secretion were not observed in the presence of fumonisin B1, an
      inhibitor of ceramide synthesis. CONCLUSIONS: These findings support the
      proposition that palmitate increases insulin release in the presence of 10 mM
      glucose by inhibiting PI3K activity through a mechanism that involves ceramide
      synthesis.

PMID- 18815555
TI  - The effect of synacthen on acute necrotizing pancreatitis in rats.
AB  - OBJECTIVES: This study investigates the hypothesis that an adrenocorticotropic
      hormone-analog therapy may ameliorate relative adrenal insufficiency in the early
      phase of acute necrotizing pancreatitis (NP) by boosting endogenous
      glucocorticoid production. METHODS: Forty Wistar rats with taurocholate-induced
      NP were divided into 5 groups: the first group received low-dose Synacthen (0.5
      mg/kg); the second, high-dose Synacthen (5mg/kg); the third,low-dose cortisol (10
      mg/kg); the fourth, high-dose cortisol (100 mg/kg); and the fifth, the control
      group, received no treatment. All animals were killed after 6 hours:
      concentrations of plasma corticosterone, interleukin 1 (IL-1), IL-6, IL-10, tumor
      necrosis factor alpha, amylase, and lipase in ascites, myeloperoxidase activity
      in the pancreas, and a histological score were evaluated. RESULTS: Corticosterone
      increased neither in the low-dose nor in the high-dose Synacthen group. Synacthen
      did not improve the early course of NP in terms of laboratory and histological
      results. A reduction of pancreatic necrosis and inflammation was observed in the
      low-dose cortisol group. CONCLUSIONS: Endogenous glucocorticoid release seemed to
      be at its maximum during the early stage of NP and could not be further increased
      by Synacthen. Low-dose exogenous cortisol ameliorated the disease. These findings
      support the existence of relative adrenal insufficiency in the early phase of
      acute NP.

PMID- 18815556
TI  - Pancreas carcinoma antigen fused to invariant chain elicits T-cell response and
      tumor growth inhibition.
AB  - OBJECTIVES: The major histocompatibility complex class II chaperone invariant
      chain (Ii) is widely used as a carrier for inserted antigenic sequences and their
      introduction into the class II processing pathway. The tumor-associated antigen
      core 2beta 1,6 N-acetylglucosaminyltransferase (C2GnT), a glycosyltransferase
      present in human pancreatic tumor cells, is not expressed by normal pancreatic
      tissues. METHODS: A set of expression vectors was engineered where the class II
      binding region of Ii was replaced by C2GnT-derived sequences. We investigated in
      vitro whether dendritic cells transfected with Ii-C2GnT constructs were capable
      to stimulate proliferation of CD4 T cells. We also tested whether vaccination
      with Ii-C2GnT would protect mice from tumor development. RESULTS: Invariant chain
      C2GnT fusion proteins bind to human DR1, DR3, DR4 and to mouse I-A molecules. Our
      results demonstrate that the plasmid DNA encoding the C2GnT epitope embedded in
      Ii induces tumor-specific T-cell responses. Mice immunized with the Ii constructs
      showed reduced growth of Panc02 pancreatic tumor cells. CONCLUSIONS: Therefore,
      Ii clipped with the tumor-associated antigen C2GnT shows promise for the
      treatment of pancreatic cancer.

PMID- 18815557
TI  - Pancreatic ischemia/reperfusion injury: impact of different preservation
      temperatures.
AB  - OBJECTIVES: Pancreatic ischemia/reperfusion injury (IRI) can influence the
      results after transplantation. Temperature during ischemia can affect IRI. A
      temperature of 4 degrees C is assumed as optimal for graft preservation. There
      are no data about the impact of different ischemia temperatures in pancreatic
      IRI. METHODS: Ischemia/reperfusion injury was induced in pancreatic tail segments
      (2-hour ischemia, 2-hour reperfusion), with rats (7/group) without ischemia
      served as control. Animals were randomized to the different experimental groups.
      To achieve the desired temperature (4, 18, or 37 degrees C and 37 degrees C
      control), pancreatic tail segments were superfused with temperated saline. After
      reperfusion, microcirculation was observed by intravital fluorescence microscopy.
      Functional capillary density (FCD), leukocyte adherence in post-capillary
      venules, and histological damage were analyzed. RESULTS: In IRI groups, decrease
      of FCD 1 and 2 hours after reperfusion compared with baseline measurements was
      significant. Functional capillary density in 4 degrees C was better as compared
      with 18 and 37 degrees C after reperfusion. Lower adherent leukocytes were seen
      in 4 and 18 degrees C, compared with 37 degrees C and also to CO. In 4 degrees C,
      histological damage was lower as compared with 18 and 37 degrees C. CONCLUSIONS:
      We could demonstrate that also in pancreatic IRI, tissue injury is temperature
      dependent. Compared with 37 degrees C, although a protective effect is
      established already at 18 degrees C, more protection is achieved with storage at
      4 degrees C. Our data suggest that 4 degrees C has the best protective effect on
      pancreatic IRI.

PMID- 18815559
TI  - Prognosis of invasive intraductal papillary mucinous neoplasm.

PMID- 18815560
TI  - Comments on "Clinical value of monitoring plasma octreotide levels during chronic
      octreotide long-acting repeatable therapy in carcinoid patients".

PMID- 18815562
TI  - Octreotide LAR in carcinoid: how to dose?

PMID- 18815565
TI  - A novel multipurpose monoclonal antibody for evaluating human c-Met expression in
      preclinical and clinical settings.
AB  - The inappropriate expression of the c-MET cell surface receptor in many human
      solid tumors necessitates the development of companion diagnostics to identify
      those patients who could benefit from c-MET targeted therapies. Tumor tissues are
      formalin fixed and paraffin embedded (FFPE) for histopathologic evaluation,
      making the development of an antibody against c-MET that accurately and
      reproducibly detects the protein in FFPE samples an urgent need. We have
      developed a monoclonal antibody (mAb), designated MET4, from a panel of MET-avid
      mAbs, based on its specific staining pattern in FFPE preparations. The accuracy
      of MET4 immunohistochemistry (MET4-IHC) was assessed by comparing MET4-IHC in
      FFPE cell pellets with immunoblotting analysis. The technical reproducibility of
      MET4-IHC possessed a percentage coefficient of variability of 6.25% in intra
      assay and interassay testing. Comparison with other commercial c-MET antibody
      detection reagents demonstrated equal specificity and increased sensitivity for c
      MET detection in prostate tissues. In cohorts of ovarian cancers and gliomas,
      MET4 reacted with ovarian cancers of all histologic subtypes (strong staining in
      25%) and with 63% of gliomas. In addition, MET4 bound c-MET on the surfaces of
      cultured human cancer cells and tumor xenografts. In summary, the MET4 mAb
      accurately and reproducibly measures c-MET expression by IHC in FFPE tissues and
      can be used for molecular imaging in vivo. These properties encourage further
      development of MET4 as a multipurpose molecular diagnostics reagent to help to
      guide appropriate selection of patients being considered for treatment with c-MET
      antagonistic drugs.

PMID- 18815566
TI  - Effect of storage on p63 immunohistochemistry: a time-course study.
AB  - One of the problems with immunohistochemistry is that storage of unstained slides
      can have a detectable negative effect on the intensity of staining for various
      antigens. This has not been well studied for the p63 antigen. A time-course study
      was performed to evaluate the effect of storage on the intensity of p63
      immunohistochemical staining. Slides from various breast lesions/foci were
      stained with a p63 antibody on day 0 and after storage at room temperature for 2,
      4, and 8 weeks. A p63 intensity score, ranging from 0 to 300, was calculated
      using the intensity (0, 1, 2, or 3+) and percentage of peripheral myoepithelial
      cell staining (0% to 100%). There was a progressive decline in the p63 intensity
      score with time with the differences between day 0 and 2 weeks and 2 and 4 weeks
      being statistically significant (P=0.037 and 0.001, respectively), whereas that
      between 4 and 8 weeks was not (P=0.075). These findings confirm a time-dependent
      decline in p63 immunostaining intensity evident as early as with 2 weeks of
      storage and still present after 8 weeks. This should be considered in the
      evaluation of p63 immunostains performed on stored unstained sections, both in
      diagnostic surgical pathology and in translational research studies.

PMID- 18815567
TI  - Translocations involving MUM1 are rare in diffuse large B-cell lymphoma.
AB  - Diffuse large B-cell lymphoma (DLBCL) comprises a diverse group of neoplasms that
      have recently been subdivided by gene expression profiling and
      immunohistochemical studies into at least 2 subgroups [germinal center (GC) type
      and non-GC type]. The non-GC subtype has a post-GC activated phenotype and
      typically expresses MUM1 by immunohistochemistry. We hypothesized that MUM1 may
      be dysregulated/up-regulated in these tumors by a chromosomal translocation, as
      is seen in many cases of plasma cell myeloma [where MUM1 is juxtaposed with the
      immunoglobulin heavy chain gene (IgH)]. Therefore, using a novel MUM1 break-apart
      probe constructed in our laboratory, we performed fluorescence in situ
      hybridization on 33 cases of DLBCL (17 GC type and 16 non-GC type) for a MUM1
      translocation. We identified 1 case of a MUM1 translocation out of 31 cases with
      successful fluorescence in situ hybridization. This case was a non-GC DLBCL
      (1/15). We conclude that genetic abnormalities involving MUM1 are rare in DLBCL
      and that a mechanism of deregulation of the MUM1 protein other than by a
      translocation event is involved in the majority of non-GC cases.

PMID- 18815568
TI  - Are acute effects of maximal dynamic contractions on upper-body ballistic
      performance load specific?
AB  - This study investigated the acute effects of upper-body maximal dynamic
      contractions on maximal throwing speed with 0.55- and 4-kg medicine balls. It was
      hypothesized that heavy preloading would transiently improve throwing performance
      only when overcoming the heavier of the two loads. Twenty-three male volunteers
      were randomly allocated into experimental (n = 11) and control (n = 12) groups.
      Both groups performed initial and final seated medicine ball throws from the
      chest, and the maximal medicine ball speed was measured by means of a radar gun.
      Between the two measurements, the control group rested passively for 15 minutes,
      and the experimental group performed three sets of three-repetition maximum bench
      presses. For the 0.55-kg load, a 2 x 2 repeated-measures analysis of variance
      revealed no significant effect of time x group interaction (p = 0.22), as well as
      no significant time (p = 0.22) or group (p = 0.72) effects. In contrast, for the
      4-kg load, a significant time x group interaction (p = 0.004) and a significant
      time (p = 0.035) but not group (p = 0.77) effect were observed. Analysis of
      simple main effects revealed that the experimental group significantly (8.3%; p <
      0.01) improved maximal throwing speed with the 4-kg load. These results support
      our research hypothesis and suggest that the acute effects of heavy preloading on
      upper-body ballistic performance might be load specific. In a practical sense,
      our findings suggest that the use of upper-body heavy resistance exercise before
      ballistic throwing movements against moderate external loads might be an
      efficient training strategy for improving an athlete's upper-body explosive
      performance.

PMID- 18815569
TI  - The influence of multiple administration of a psychomotor test on performance and
      learning.
AB  - Exercise scientists frequently use criterion measure tests to assess levels of
      motor performance and physical fitness or to evaluate the success of their
      intervention programs. During this process, the same motor test might be
      administered multiple times. The aim of the present study was to examine whether
      familiarization with a psychomotor test would influence performance and/or
      learning. One hundred thirty (n = 130) primary school students participated in
      the study. Participants were randomly divided into two groups, experimental (n =
      60, mean age = 10.74 years old, minimum = 9.08, maximum = 11.83) and control (n =
      70, mean age = 10.68 years old, minimum = 9.5, maximum = 11.79). The flamingo
      balance test was used to examine the postulated hypothesis. Initially, both
      groups executed the balance test. Then, only the experimental group performed two
      additional trials, one trial every 3 days. A final trial was administered to all
      participants, followed by a retention trial 1 week later. The results revealed
      that both groups improved their performance. The experimental group outperformed
      the control group. The retention trial showed that performance levels for both
      groups continued to improve, suggesting that familiarization with the test
      influenced not only performance but learning as well. Exercise scientists who
      implement psychomotor tests, such as balance tests, for evaluative purposes
      should be aware that performance improvement does not necessary represent changes
      in individuals' performance, but it may reflect individuals' familiarization with
      the test.

PMID- 18815570
TI  - Validity and reliability of the medicine ball throw for kindergarten children.
AB  - The purpose of this study was to establish validity and reliability evidence for
      the medicine ball throw test for kindergarten students, an underrepresented group
      in the literature. The subjects were 105 students, 5-7 years old, BMI 17.44 +/-
      3.17 kg x m(-2), 43% female and 57% male. Intraclass correlation coefficients
      (ICCs) were used to examine reliability, and Pearson correlation coefficients and
      a paired t-test were used to examine validity. To accomplish this, the
      kindergarten students completed the medicine ball throw test on two different
      days and the modified pull-up test, the "criterion" measure, on another day. For
      the medicine ball throw, each student sat on the floor before throwing the
      medicine ball forward like a chest pass three times. The medicine ball throw was
      highly reliable both within 1 day (ICCs = 0.93 and 0.94 for day 1 and day 2,
      respectively) and across 2 days (ICC = 0.88), with all reliability estimates over
      the acceptable level of 0.80. The medicine ball throw scores were positively
      related with height (r = 0.34) and weight (r = 0.34), and there was a significant
      difference between the 5-year-old group (mean +/- SD; 111.78 +/- 34.93) and the 6
      year-old group (135.60 +/- 39.77), t = -3.23, p = 0.002, which supports
      correlational and known-difference evidence of validity for the medicine ball
      throw test. Even though no correlation was found between the medicine ball throw
      test and the modified pull-up test, r = -0.04, other forms of validity evidence
      (i.e., known-difference and correlational) were apparent. In conclusion, the
      medicine ball throw test seems to be a valid and reliable measure of upper-body
      strength for kindergarten children.

PMID- 18815571
TI  - Eight weeks of ballistic exercise improves power independently of changes in
      strength and muscle fiber type expression.
AB  - This study investigated the effects of ballistic resistance training and strength
      training on muscle fiber composition, peak force (PF), maximal strength, and peak
      power (PP). Fourteen males (age = 21.3 +/- 2.9, body mass = 77.8 +/- 10.1 kg)
      with 3 months of resistance training experience completed the study. Subjects
      were tested pre and post for their squat one-repetition maximum (1RM) and PP in
      the jump squat (JS). Peak force and rate of force development (RFD) were tested
      during an isometric midthigh pull. Muscle biopsies were obtained from the vastus
      lateralis for analysis of muscle fiber type expression. Subjects were matched for
      strength and then randomly selected into either training (T) or control (C)
      groups. Group T performed 8 weeks of JS training using a periodized program with
      loading between 26 and 48% of 1RM, 3 days per week. Group T showed significant
      improvement in PP from 4088.9 +/- 520.6 to 5737.6 +/- 651.8 W. Rate of force
      development improved significantly in group T from 12687.5 +/- 4644.0 to 25343.8
      +/- 12614.4 N x s(-1). PV improved significantly from 1.59 +/- 0.41 to 2.11 +/-
      0.75 m x s(-1). No changes occurred in PF, 1RM, or muscle fiber type expression
      for group T. No changes occurred in any variables in group C. The results of this
      study indicate that using ballistic resistance exercise is an effective method
      for increasing PP and RFD independently of changes in maximum strength (1RM, PF),
      and those increases are a result of factors other than changes in muscle fiber
      type expression.

PMID- 18815572
TI  - The effects of proprioceptive neuromuscular facilitation and dynamic stretching
      techniques on vertical jump performance.
AB  - The purpose of this study was to investigate the effects of 3 different warm-ups
      on vertical jump performance. The warm-ups included a 600-m jog, a 600-m jog
      followed by a dynamic stretching routine, and a 600-m jog followed by a
      proprioceptive neuromuscular facilitation (PNF) routine. A second purpose was to
      determine whether the effects of the warm-ups on vertical jump performance varied
      by gender. Sixty-eight men and women NCAA Division I athletes from North Dakota
      State University performed 3 vertical jumps on a Just Jump pad after each of the
      3 warm-up routines. The subjects were split into 6 groups and rotated between 3
      warm-up routines, completing 1 routine each day in a random order. The results of
      the 1-way repeated measures analysis of variance showed no significant
      differences in the combined (p = 0.927), men's (p = 0.798), or women's (p =
      0.978) results. The results of this study showed that 3 different warm-ups did
      not have a significant affect on vertical jumping. The results also showed there
      were no gender differences between the 3 different warm-ups.

PMID- 18815573
TI  - Lessons from the modern battlefield: successful upper extremity injury
      reconstruction in the subacute period.
AB  - BACKGROUND: Reconstructive techniques and protocols for limb salvage of upper
      extremity battlefield injuries remains poorly defined. Our study describes the
      types of flaps, the timing of reconstruction, and success rates of war upper
      extremity reconstruction during a 30-month period using the Bethesda limb salvage
      protocol. METHODS: Soldiers with significant upper extremity injuries with
      complex open fractures from Operation Iraqi Freedom and Operation Enduring
      Freedom-Afghanistan who underwent tissue transfer flaps were reviewed (n = 26,
      free flaps n = 6). Data analysis included mechanism of injury, associated
      injuries, types of flap, postoperative complications, wound infection rates, and
      outcome data. RESULTS: The cause of injury consisted of improvised explosive
      device (61%), rocket-propelled grenades (15%), motor vehicle crash (8%), land
      mine (8%), and gunshot wound (4%). Mean age was 25 years. Mean number of
      prereconstructive washouts was six (range, 3-22). Forty-six percent of wounds
      were culture positive at admission (75% were Acinetobacter species). All patients
      had other coexisting extremity, trunk or facial injuries. Average time to flap
      reconstruction was 31 days (range, 9-161). In 66% of the cases, a fasciocutaneous
      flap was used, and in the remaining cases, muscle (19%) and adipofascial (15%)
      flaps were performed. Flap success rate was 96%, with one flap loss because of
      venous congestion (managed with limb shortening). Infection rate was 8%. Complete
      coverage was achieved in all upper extremity wounds and early occupational
      therapy resulted in improved return to function. CONCLUSIONS: Despite massive
      bone and soft tissue defects, high preoperative wound colonization, and delays in
      definitive reconstruction, devastating war wounds can be successfully
      reconstructed in the subacute period with low flap failure, infection, and
      amputation rates.

PMID- 18815574
TI  - Immunmodulation of serum in orthopaedic trauma.
AB  - BACKGROUND: The aim of this study was to test the hypothesis that inhibitory
      substances circulating in the patient's serum after trauma might impair leukocyte
      function by evaluating the effect of such serum on cytokine release in a whole
      blood model. METHODS: Hip replacement surgery was considered a standardized
      musculoskeletal trauma, and seven women and three men undergoing elective total
      hip replacement were included in the study. Ex vivo lipopolysaccharide (LPS) and
      peptidoglycan (PepG) induced tumor necrosis factor-alpha (TNF-alpha) and
      interleukin (IL-10) releases were measured in whole blood sampled preoperatively
      and added serum taken before, at the end of operation and at postoperative day 1
      and 6. Saline was used as negative control to serum. RESULTS: LPS and PepG
      induced a significant release of TNF-alpha and IL-10 in whole blood. Addition of
      preoperative serum, postoperative serum or day 1 postoperative serum did not
      alter the LPS-induced release of TNF-alpha as compared with saline control.
      Addition of preoperative serum significantly increased the PepG-induced release
      of TNF-alpha as compared with saline control (p = 0.011). This increase was not
      significantly changed with addition of postoperative serum or day 1 postoperative
      serum. When serum from postoperative day 6 was added, both LPS and PepG induced
      expression of TNF-alpha was significantly reduced as compared with preoperative
      serum (p = 0.018 and 0.008, respectively). Preoperative serum also increased the
      PepG induced expression of IL-10 (p = 0.007) in relation to saline control, and
      this increase was not significantly changed by addition of postoperative serum or
      day 1 and day 6 postoperative serum. Neither of the serum samples altered the LPS
      induced expression of IL-10 as compared with saline control (p = 0.212).
      CONCLUSION: Our data show that in trauma patients, serum expresses activity that
      inhibits LPS and PepG induced release of TNF-alpha in a whole blood model, and
      our study, then, corroborates the hypothesis that inhibitory substances
      circulating in the patients' serum after trauma impair leukocyte function.

PMID- 18815575
TI  - Complete thoracic cage disruption associated with anterior lung herniation.

PMID- 18815576
TI  - Successful nystatin powder treatment of posttraumatic invasive Aspergillus
      fumigatus wound infection refractory to systemic antifungal therapy.

PMID- 18815577
TI  - Sonographic depiction of posttraumatic alveolar-interstitial disease: the hand
      held diagnosis of a pulmonary contusion.

PMID- 18815578
TI  - Complete bilateral tracheobronchial disruption in a child with blunt chest
      trauma.

PMID- 18815579
TI  - Use of combined modified Mason-Allen and perimeter stitches for repair of a
      quadriceps femoris laceration: a case report.

PMID- 18815580
TI  - Intracorporeal laparoscopic management of mesenteric avulsion in a blunt trauma
      patient.

PMID- 18815581
TI  - Pellet embolization to the heart presenting as a massive myocardial infarction.

PMID- 18815582
TI  - Neural representation of preference relationships.
AB  - This paper indicates that the human product-preference relationship can, using a
      product selection task, be predicted to an extent on the basis of changes in the
      oxygenated hemoglobin concentration in the ventromedial prefrontal cortex and
      that functional near-infrared spectroscopy allows this prediction despite the
      shallow depth at which brain information is measured. A Bayesian three-layer
      perceptron was used as a predictive model. Results of this work help to lay the
      foundations for the concept of utility in economics and marketing theories from
      the perspective of neuroscience and have important significance from a practical
      standpoint as well.

PMID- 18815583
TI  - Neuromagnetic responses in silence after musical chord sequences.
AB  - Neuromagnetic responses in silence after chord sequences ending in three kinds of
      musical cadences were investigated. The magnetoencephalographic signals of
      musically trained participants showed clear peaks around the bilateral temporal
      areas during the period of silence when the cadences were musically premature.
      Maximum global moment during the silent period was estimated in the auditory
      cortices. The time course of the source activities revealed two components, first
      around 80 ms and second around 150 or 200 ms, the latency of which differed
      depending on the cadence. These auditory cortical activities, particularly the
      second components, are suggested to reflect the participants' internal generation
      of a sound image associated with temporal or temporal-spectral expectations
      induced as a function of musical cadence.

PMID- 18815584
TI  - Multipotency of human neural stem cells from fetal striatum.
AB  - We had reported that neural stem cells from human fetal striatum (hsNSCs)
      expressed neural stem cell markers, and were capable of differentiation into
      neurons, astrocytes, and oligodendrocytes in vitro. To examine multipotency of
      hsNSCs, some experiments of transgerm layer differentiation in vitro were carried
      out. Our data indicated that hsNSCs could also generate osteocytes, adipocytes,
      and hepatocyte-like cells in vitro. Meanwhile, we injected hsNSCs into murine
      blastocysts at embryonic day 3.5 of gestation. Microinjection of hsNSCs led to
      the generation of chimeric embryos. Embryos at embryonic day 3.5 of gestation
      were shown to contribute to the hsNSC-derived cells by PCR-southern blot of
      17alphamod, a special method to discover human cells from animals. Analysis of
      the donor distribution in different tissues showed that donor-derived cells
      seeded to various tissues. The cellular nature of the human donor cells in
      chimeric tissues is, however, currently unknown, and further work will be done to
      identify what differentiated phenotypes have developed from the human cells.

PMID- 18815585
TI  - Induction of fibroblast growth factor-2 by electrical stimulation in cultured
      retinal Mueller cells.
AB  - It has been demonstrated that retinal Mueller cells, the predominant glial cells,
      produce neurotrophic factors including basic fibroblast growth factor (FGF-2),
      and that electrical stimulation enhances the transcription of FGF-2 in the
      central nervous system. In this study, the effect of electrical stimulation on
      the induction of FGF-2 in cultured rat Mueller cells was investigated by
      quantitative real-time polymerase chain reaction and western blotting. Both the
      messenger RNA and protein of FGF-2 were significantly upregulated after
      electrical stimulation compared with that of controls. These results suggest that
      electrical stimulation may directly induce the production of FGF-2 in the retina.

PMID- 18815586
TI  - Carbon monoxide-prostaglandin E2 interaction in the hypothalamic circulation.
AB  - The heme oxygenase (HO)-carbon monoxide pathway was earlier shown to increase
      hypothalamic blood flow after inhibition of nitric oxide synthesis in rats. We
      hypothesized that this effect is mediated by prostaglandin E2 (PGE2). Inhibition
      of constitutive HO activity decreased cerebral PGE2 production and simultaneously
      increased hypothalamic nitric oxide synthase (NOS) activity without changing
      hypothalamic blood flow. Furthermore, HO blockade induced cyclooxygenase
      dependent decrease and NOS-mediated increase of the hypothalamic blood flow after
      inhibition of NOS and cyclooxygenase, respectively. Therefore, constitutive
      carbon monoxide release seems to have two indirect effects on the hypothalamic
      circulation: vasodilation mediated by PGE2 and vasoconstriction as a result of
      NOS inhibition.

PMID- 18815587
TI  - Impaired recovery of dysferlin-null skeletal muscle after contraction-induced
      injury in vivo.
AB  - The protein, dysferlin, mediates sarcolemmal repair in vitro, implicating
      defective membrane repair in dysferlinopathies. To study the role of dysferlin in
      vivo, we assessed contractile function, sarcolemmal integrity, and myogenesis
      before and after injury from large-strain lengthening contractions in dysferlin
      null and control mice. We report that dysferlin-null muscles produce higher
      contractile torque, and are equally susceptible to initial injury but recover
      from injury more slowly. Two weeks after injury, control muscles retain
      fluorescein dextran and do not show myogenesis. Dysferlin-null muscles do not
      retain fluorescein dextran, and show necrosis followed by myogenesis. Our data
      indicate that recovery of control muscles from injury primarily involves
      sarcolemmal repair whereas recovery of dysferlin-null muscles primarily involves
      myogenesis without repair and long-term survival of myofibers.

PMID- 18815588
TI  - Auditory word perception in sentence context in reading-disabled children.
AB  - Reading difficulties seem to be related to a phonological deficit that has its
      origin in poor speech perception. As such, disabled readers may use contextual
      cues to compensate for their weak speech perception abilities. We compared good
      and poor readers, 7-13 years old, on auditory perception of words varying in
      phonological contrast, in congruent versus incongruent sentence contexts. Both
      groups did worse in the phonologically similar than in the phonologically
      dissimilar incongruent condition. Magnetoencephalography revealed differential
      activation between the groups as a function of phonological contrast in left
      superior temporal gyrus between 200 and 300 ms, suggesting that poor readers may
      have processed phonologically similar incongruent stimuli as congruent. The
      results are consistent with a phonological account of reading disability.

PMID- 18815589
TI  - A paucimorphic variant in the HMG-CoA reductase gene is associated with lipid
      lowering response to statin treatment in diabetes: a GoDARTS study.
AB  - BACKGROUND: Considerable interindividual variation exists in cholesterol-lowering
      response to 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) inhibitors
      (statins). HMGCR catalyzes the rate-limiting step in cholesterol biosynthesis,
      and also plays a significant role in cholesterol homeostasis. We evaluated the
      association of a single nucleotide polymorphism (rs17238540) in the HMGCR gene
      with lipid-lowering response to statins in a large population-based cohort of
      patients with diabetes. METHODS: One thousand six hundred and one patients
      commencing statins between 1993 and 2006 were identified from the Genetics of
      Diabetes Audit and Research in Tayside Scotland database. Statin response was
      determined by both percentage change in lipids, and whether patients failed to
      reach a total cholesterol target of less than or equal to 4 mmol/l. Covariates
      included HMGCR genotype, baseline lipids, age, sex, adherence and statin dose.
      All patients were genotyped for rs17238540 using a TAQMAN-based allelic
      discrimination assay. RESULTS: Twenty-eight percent of individuals homozygous for
      the more frequent T allele failed to reach target compared with 51% of the
      individuals with a single copy of the minor G allele (carrier frequency 3.3%),
      with an adjusted odds ratio (95% confidence interval) for failure of 2.93 (1.61
      5.34) mmol/l, P = 0.0005. In addition, we found that the heterozygotes had a 13%
      smaller reduction in total cholesterol (-32.3 vs. -37.1%, P = 0.0081) and a 27%
      smaller reduction in triglycerides (-27.5 vs. -37.6%, P = 0.0046). CONCLUSION:
      Individuals heterozygous for the G allele of rs17238540 in the HMGCR gene may
      respond less well to statin therapy in terms of total cholesterol and
      triglyceride lowering.

PMID- 18815590
TI  - Characterization of intron-1 haplotypes of the G protein beta 4 subunit gene-
      association with survival and progression in patients with urothelial bladder
      carcinoma.
AB  - PURPOSE: Polymorphisms in genes encoding subunits of heterotrimeric G proteins
      have been repeatedly associated with various cancers. As G beta gamma signaling
      is presumed to be involved in proliferation and invasion processes, we analyzed
      genetic variations in regulatory regions of GNB4, which encodes the G beta 4
      subunit, for their potential influence on cancer progression. EXPERIMENTAL
      DESIGN: We characterized the promoter of GNB4 and screened the promoter as well
      as exon 1 and intron 1 for single nucleotide polymorphisms by sequencing 100
      healthy controls. Following a haplotype analysis, we determined the functional
      impact upon gene expression of the defined haplotypes by reporter assays,
      electrophoretic mobility shift assay and western blot. In addition, these
      haplotypes were tested for their relation to the disease course of urothelial
      bladder cancer. RESULTS: Whereas the promoter of GNB4 revealed no polymorphisms,
      33 single nucleotide polymorphisms located in exon 1 and intron 1 were identified
      and together with a common exon-4 polymorphism implemented in haplotype analysis,
      which resulted in the determination of distinct haplotype blocks. Reporter
      activity was haplotype-dependently different (P=0.001). 1*1/1*1 showed increased
      G beta 4 protein (P=0.003), and bladder cancer patients carrying this diplotype
      displayed more progressive disease (P=0.046) and a significantly increased
      mortality (P=0.046). In multivariate analysis,the diplotypes were independent
      prognostic factors for survival and progression. CONCLUSION: Intron-1 haplotypes
      of GNB4 may, thus, serve as predictive markers for progression and survival of
      patients suffering from bladder cancer.

PMID- 18815591
TI  - Dose-response of ritonavir on hepatic CYP3A activity and elvitegravir oral
      exposure.
AB  - Ritonavir, a potent inhibitor of cytochrome P450 isoform 3A (CYP3A) activity, is
      frequently used to boost the effects of protease inhibitors at doses of 100-400
      mg per day; however, human data regarding the optimal dose required for boosting
      are limited. This study systematically evaluated the ritonavir dose-response
      relationship on presystemic and systemic CYP3A metabolism using the human
      immunodeficiency virus integrase inhibitor elvitegravir and midazolam as probe
      substrates. Ritonavir administered once daily with elvitegravir exhibited
      nonlinear pharmacokinetics, with a 119-fold increase in the area under the plasma
      concentration-time curve over the dosing interval over a 20- to 200-mg dose
      range. The 20-mg dose of ritonavir substantially reduced CYP3A-mediated clearance
      (CL), as evidenced by a 66% reduction in midazolam CL that plateaued to 17% of
      baseline activity at a 100-mg dose. Maximum inhibition of elvitegravir apparent
      oral CL was achieved with ritonavir doses of 50-100 mg. Elvitegravir and
      ritonavir were generally well tolerated in this study. These data provide a
      critical understanding of ritonavir's dose-response relationship for inhibition
      of CYP3A activity in humans.

PMID- 18815592
TI  - Activity-dependent regulation of inhibitory synapse development by Npas4.
AB  - Neuronal activity regulates the development and maturation of excitatory and
      inhibitory synapses in the mammalian brain. Several recent studies have
      identified signalling networks within neurons that control excitatory synapse
      development. However, less is known about the molecular mechanisms that regulate
      the activity-dependent development of GABA (gamma-aminobutyric acid)-releasing
      inhibitory synapses. Here we report the identification of a transcription factor,
      Npas4, that plays a role in the development of inhibitory synapses by regulating
      the expression of activity-dependent genes, which in turn control the number of
      GABA-releasing synapses that form on excitatory neurons. These findings
      demonstrate that the activity-dependent gene program regulates inhibitory synapse
      development, and suggest a new role for this program in controlling the
      homeostatic balance between synaptic excitation and inhibition.

PMID- 18815593
TI  - GILT is a critical host factor for Listeria monocytogenes infection.
AB  - Listeria monocytogenes is a gram-positive, intracellular, food-borne pathogen
      that can cause severe illness in humans and animals. On infection, it is actively
      phagocytosed by macrophages; it then escapes from the phagosome, replicates in
      the cytosol, and subsequently spreads from cell to cell by a non-lytic mechanism
      driven by actin polymerization. Penetration of the phagosomal membrane is
      initiated by the secreted haemolysin listeriolysin O (LLO), which is essential
      for vacuolar escape in vitro and for virulence in animal models of infection.
      Reduction is required to activate the lytic activity of LLO in vitro, and we show
      here that reduction by the enzyme gamma-interferon-inducible lysosomal thiol
      reductase (GILT, also called Ifi30) is responsible for the activation of LLO in
      vivo. GILT is a soluble thiol reductase expressed constitutively within the
      lysosomes of antigen-presenting cells, and it accumulates in macrophage
      phagosomes as they mature into phagolysosomes. The enzyme is delivered by a
      mannose-6-phosphate receptor-dependent mechanism to the endocytic pathway, where
      amino- and carboxy-terminal pro-peptides are cleaved to generate a 30-kDa mature
      enzyme. The active site of GILT contains two cysteine residues in a CXXC motif
      that catalyses the reduction of disulphide bonds. Mice lacking GILT are deficient
      in generating major histocompatibility complex class-II-restricted CD4(+) T-cell
      responses to protein antigens that contain disulphide bonds. Here we show that
      these mice are resistant to L. monocytogenes infection. Replication of the
      organism in GILT-negative macrophages, or macrophages expressing an enzymatically
      inactive GILT mutant, is impaired because of delayed escape from the phagosome.
      GILT activates LLO within the phagosome by the thiol reductase mechanism shared
      by members of the thioredoxin family. In addition, purified GILT activates
      recombinant LLO, facilitating membrane permeabilization and red blood cell lysis.
      The data show that GILT is a critical host factor that facilitates L.
      monocytogenes infection.

PMID- 18815594
TI  - Histone H2A.Z and DNA methylation are mutually antagonistic chromatin marks.
AB  - Eukaryotic chromatin is separated into functional domains differentiated by post
      translational histone modifications, histone variants and DNA methylation.
      Methylation is associated with repression of transcriptional initiation in plants
      and animals, and is frequently found in transposable elements. Proper methylation
      patterns are crucial for eukaryotic development, and aberrant methylation-induced
      silencing of tumour suppressor genes is a common feature of human cancer. In
      contrast to methylation, the histone variant H2A.Z is preferentially deposited by
      the Swr1 ATPase complex near 5' ends of genes where it promotes transcriptional
      competence. How DNA methylation and H2A.Z influence transcription remains largely
      unknown. Here we show that in the plant Arabidopsis thaliana regions of DNA
      methylation are quantitatively deficient in H2A.Z. Exclusion of H2A.Z is seen at
      sites of DNA methylation in the bodies of actively transcribed genes and in
      methylated transposons. Mutation of the MET1 DNA methyltransferase, which causes
      both losses and gains of DNA methylation, engenders opposite changes (gains and
      losses) in H2A.Z deposition, whereas mutation of the PIE1 subunit of the Swr1
      complex that deposits H2A.Z leads to genome-wide hypermethylation. Our findings
      indicate that DNA methylation can influence chromatin structure and effect gene
      silencing by excluding H2A.Z, and that H2A.Z protects genes from DNA methylation.

PMID- 18815595
TI  - Promoter-driven splicing regulation in fission yeast.
AB  - The meiotic cell cycle is modified from the mitotic cell cycle by having a pre
      meiotic S phase that leads to high levels of recombination, two rounds of nuclear
      division with no intervening DNA synthesis and a reductional pattern of
      chromosome segregation. Rem1 is a cyclin that is only expressed during meiosis in
      the fission yeast Schizosaccharomyces pombe. Cells in which rem1 has been deleted
      show decreased intragenic meiotic recombination and a delay at the onset of
      meiosis I (ref. 1). When ectopically expressed in mitotically growing cells, Rem1
      induces a G1 arrest followed by severe mitotic catastrophes. Here we show that
      rem1 expression is regulated at the level of both transcription and splicing,
      encoding two proteins with different functions depending on the intron retention.
      We have determined that the regulation of rem1 splicing is not dependent on any
      transcribed region of the gene. Furthermore, when the rem1 promoter is fused to
      other intron-containing genes, the chimaeras show a meiotic-specific regulation
      of splicing, exactly the same as endogenous rem1. This regulation is dependent on
      two transcription factors of the forkhead family, Mei4 (ref. 2) and Fkh2 (ref.
      3). Whereas Mei4 induces both transcription and splicing of rem1, Fkh2 is
      responsible for the intron retention of the transcript during vegetative growth
      and the pre-meiotic S phase.

PMID- 18815596
TI  - ROS3 is an RNA-binding protein required for DNA demethylation in Arabidopsis.
AB  - DNA methylation is an important epigenetic mark for transcriptional gene
      silencing (TGS) in diverse organisms. Recent studies suggest that the methylation
      status of a number of genes is dynamically regulated by methylation and
      demethylation. In Arabidopsis, active DNA demethylation is mediated by the ROS1
      (repressor of silencing 1) subfamily of 5-methylcytosine DNA glycosylases through
      a base excision repair pathway. These demethylases have critical roles in erasing
      DNA methylation and preventing TGS of target genes. However, it is not known how
      the demethylases are targeted to specific sequences. Here we report the
      identification of ROS3, an essential regulator of DNA demethylation that contains
      an RNA recognition motif. Analysis of ros3 mutants and ros1 ros3 double mutants
      suggests that ROS3 acts in the same genetic pathway as ROS1 to prevent DNA
      hypermethylation and TGS. Gel mobility shift assays and analysis of ROS3
      immunoprecipitate from plant extracts shows that ROS3 binds to small RNAs in
      vitro and in vivo. Immunostaining shows that ROS3 and ROS1 proteins co-localize
      in discrete foci dispersed throughout the nucleus. These results demonstrate a
      critical role for ROS3 in preventing DNA hypermethylation and suggest that DNA
      demethylation by ROS1 may be guided by RNAs bound to ROS3.

PMID- 18815597
TI  - The science of medical education.

PMID- 18815598
TI  - Postgraduate education in women's health in New Zealand.

PMID- 18815599
TI  - Workplace bullying of junior doctors: cross-sectional questionnaire survey.
AB  - AIM: Workplace bullying is a growing concern amongst health professionals. Our
      aim was to explore the frequency, nature, and extent of workplace bullying in an
      Auckland Hospital (Auckland, New Zealand). METHOD: A cross-sectional
      questionnaire survey of house officers and registrars at a tertiary hospital was
      conducted. RESULTS: There was an overall response rate of 33% (123/373). 50% of
      responders reported experiencing at least one episode of bullying behaviour. The
      largest source of workplace bullying was consultants and nurses in equal
      frequency. The most common bullying behaviour was unjustified criticism. Only 18%
      of respondents had made a formal complaint. CONCLUSION: Workplace bullying is a
      significant issue with junior doctors. We recommend education about unacceptable
      behaviours and the development of improved complaint processes.

PMID- 18815600
TI  - Bilingual medical students as interpreters--what are the benefits and risks?
AB  - AIMS: To identify the frequency of medical students interpreting in healthcare
      settings and to explore the issues related to the use of non-professional
      interpreters. METHODS: All 4th and 5th year University of Otago medical students
      were surveyed to identify bilingual medical students who have interpreted for
      patients. Students and key informants were interviewed and audiotaped. RESULTS:
      Of the 102 bilingual students identified, 59 interpreted for patients. We
      analysed 39 student interviews. Most reported a 'good' interpreting experience
      and thought student interpreting was 'a good idea', but some encountered 'bad'
      experiences. Stakeholders (professional interpreters, DHB policy staff, and
      clinicians who use interpreters) thought students should not interpret. Issues
      explored were: student comfort, clinician's choice, the interpreter's role,
      cultural competency, awareness, and provision of interpreting services.
      CONCLUSIONS: A considerable proportion of bilingual clinical medical students
      have interpreted for patients contrary to Capital and Coast District Health Board
      policy and professional interpreter recommendations. In conjunction with
      published literature and after consulting with interpreter trainers, we have
      developed a document which canvasses the issues involved and proposed practical
      guidelines, to better prepare healthcare professionals and non-professional
      interpreters for interpreting situations. More research is required to find out
      why clinicians are asking medical students and others to interpret rather than
      engaging professional interpreters.

PMID- 18815601
TI  - Future practice of graduates of the New Zealand Diploma of Obstetrics and
      Gynaecology or Certificate in Women's Health.
AB  - AIM: To determine: why Diploma of Obstetrics (DipObs), Diploma of Obstetrics and
      Medical Gynaecology (DipOMG), or Certificate in Women's Health graduates
      enrolled; course usefulness; and subsequent practice. METHODS: 588 University of
      Otago DipObs, DipOMG, and Certificate in Women's Health graduates (1992-2006)
      plus Auckland University graduates (1996-2006) were identified. All were doctors.
      Questionnaires were sent to the 477 with New Zealand medical registration and
      responses analysed. RESULTS: 334 of the 477 graduates returned completed
      questionnaires--70% response rate. 73% had worked as GPs, 10% at family planning
      clinics, 6% at sexual health clinics; and 13% specialised in OandG. 80% enrolled
      to further knowledge in women's health, 20% in children's health, and 43% to
      practise GP obstetrics. Most respondents who enrolled in the 1990s intended to
      practise GP obstetrics but by 2000 most did not. Of 137 New Zealand-based GP
      respondents who enrolled to practise GP obstetrics, only 5 (3.6%) currently
      practise intrapartum obstetric care. Twenty-three GPs still practise shared
      maternity care. Of 220 primary care practitioners, 90% provide early antenatal
      care. 93% described the course as useful-extremely useful. CONCLUSIONS: The
      DipObs, Dip OMG and Certificate in Women's Health have continued to provide
      useful postgraduate training in women's health during a changing time in New
      Zealand pregnancy care. While many graduates of the 1990s enrolled to practise GP
      obstetrics, most recent graduates did not, and few GPs still practise intrapartum
      obstetrics.

PMID- 18815602
TI  - Is incidental Meckel's diverticulum resected safely?
AB  - AIM: Meckel's diverticulum (MD) is the most common congenital anomaly of the
      small intestine. The majority of MD cases are discovered incidentally. On the
      other hand, there is disagreement about the management of incidentally discovered
      asymptomatic MD. The aim of the study was to compare the clinicopathologic
      characteristics of incidentally found and symptomatic cases of MD, and to compare
      morbidity and mortality in symptomatic and asymptomatic patients. PATIENTS AND
      METHODS: Records of patients whose MD was resected at our institution between
      1989 and 2004 were reviewed and 76 patients were found. The patients were divided
      into two groups. The incidental group included patients in whom the MDs were
      found incidentally during the course of laparotomy performed for reasons not
      related to the diverticular complications. The symptomatic group included
      patients who presented with complications related to the MDs. We compared the
      clinicopathologic characteristics of the patients between the two groups RESULTS:
      The incidental group included 40 patients (34 males) and the symptomatic group
      included 36 patients (30 males). There was no significant difference between the
      two groups with respect to age, gender, APACHE scores, postoperative
      complications, and hospital stay. There were two deaths in the symptomatic group.
      There was a significant correlation between operative mortality and APACHE II
      scores. CONCLUSIONS: Resection of incidentally found MD is not associated with
      increased operative morbidity or mortality.

PMID- 18815603
TI  - Shifting perceptions and challenging the profession's paradigms: reflections from
      an undergraduate week of population health.
AB  - The perception that population health is a poor cousin of the clinically
      orientated medical specialties has occurred despite a growing acknowledgement of
      the importance of a population health approach to the provision of medical care
      in the 21st Century. This perception appears entrenched within academic and
      clinical institutions, and is inherited by undergraduate students as they move
      through their training. Competing philosophies within modern medical curricula,
      medical socialisation, and historical professional belief structures have all
      contributed to both a covert and an overt scepticism towards population based
      approaches as being 'soft' and largely irrelevant. In May 2007, the University of
      Auckland introduced a new initiative for Year 5 medical students, called
      'Population Health Intensive'. This was a week aimed at increasing medical
      undergraduate student's exposure to population health perspectives and
      initiatives. It challenged students and academic staff alike to reflect on their
      perceptions of the role of population health in medical practice and raised
      questions about the relevance of current medical education in light of the
      changing face of health and healthcare delivery. In this paper we consider the
      drivers of change and argue that population health has an important and
      legitimate place in both undergraduate medical training and clinical practice,
      thus widening the professions' understanding of health and disease.

PMID- 18815604
TI  - What can the history tell us? An argument for observed history-taking in the
      trainee intern long case assessment.
AB  - History-taking is one of the most important clinical skills for the medical
      student to learn and remains the core component of a doctor's diagnostic
      'toolkit'. Yet, it is one of the most difficult clinical skills to assess.
      Clinical assessment at a trainee intern level has typically focussed on
      examination skills, and case presentation, which are more easily measured.
      History-taking is assumed to be of an adequate standard on the basis of the case
      presentation rather than by direct observation. In this paper we discuss the
      importance of assessing the patient-doctor encounter directly through
      observation, in the context of the trainee intern long case examination. Despite
      changing assessment trends in medical education, these authors argue for the
      retention of the long case as an assessment tool for final year medical students
      on the basis of its high face validity and close resemblance to "real life"
      patient encounters. However, we believe addition of an observing examiner during
      the history-taking and physical examination augments the inherent value of the
      longcase and is recommended in order to increase the reliability of the
      assessment. Observation allows for direct assessment of the student-patient
      interaction and the hypothetico-deductive approach taken by the student to
      diagnosis. It provides opportunity to reconcile the multiple interactions
      occurring between the context and the construct (skills and knowledge) measured
      in an assessment. Importantly, at a trainee intern level it provides students
      with a final opportunity to receive feedback on their history taking and
      diagnostic skills, an integral part of all medical practice, prior to their
      graduation as junior doctors.

PMID- 18815605
TI  - The folly of rewarding silence while hoping for open reporting of adverse medical
      events--how to realign the rewards.
AB  - The recent release under the Official Information Act (OIA) of Capital and Coast
      District Health Board's (CandC DHB) Serious and Sentinel Event Report, the
      subsequent national report, and the commitment to fund a New Zealand-wide
      incident reporting system raise a number of important issues. This paper
      discusses the barriers to incident reporting and the folly of attempting to
      reward system improvements while the barriers are still in place. Suggestions are
      also made to help guide the development of appropriate systems which will
      eliminate barriers and realign the rewards.

PMID- 18815606
TI  - Superior canal benign positional vertigo.

PMID- 18815607
TI  - Medical image. Fatal tyre blast injuries including bowel evisceration and forearm
      amputation.

PMID- 18815608
TI  - Medical image. An unusual cause of left iliac fossa mass.

PMID- 18815609
TI  - Medical image. Ruptured globe.

PMID- 18815610
TI  - Successful therapy for a patient with an infected ascending aortic graft and
      sternal osteomyelitis without graft removal.
AB  - OBJECTIVE: Following open-heart surgery, sternal osteomyelitis or infection of
      the graft may be a serious complication with high mortality rates. The
      recommended treatment of an infected graft is its explantation. Because of the
      poor performance status of the patient, this may not always be an option. We
      report a successful treatment concept without removal of the infected graft.
      METHODS: The infected ascending aortic graft and the remaining sternum of a
      critically ill 60-year-old man were covered with a bilateral pectoralis muscle
      flap. RESULTS: Postoperatively, the laboratory test values normalized and the
      patient was discharged 1 month after the intervention. One year after surgery,
      the patient was in good condition and the examination showed no signs of
      infection. CONCLUSION: The thus demonstrated treatment concept with insertion of
      well-vascularized tissues in combination with a specific antibiotic regime in our
      hands proved to be an additional option for the successful management of life
      threatening infections of a sternal osteomyelitis in combination of an infected
      aortic graft.

PMID- 18815611
TI  - Pilot study of diagnostic potential of the Mycobacterium tuberculosis recombinant
      HBHA protein in a vaccinated population in Finland.
AB  - BACKGROUND: In recent years T cell based interferon gamma release assays (IGRA)
      have been developed for immunodiagnosis of M. tuberculosis infection. At present
      these assays do not discriminate between disease and latency. Therefore, more
      promising antigens and diagnostic tools are continuously being searched for
      tuberculosis immunodiagnostics. The heparin binding hemagglutinin (HBHA) is a
      surface protein of M. tuberculosis which promotes bacterial aggregation and
      adhesion to non-phagocytic cells. It has been previously assumed that native,
      methylated form of this protein would be a promising antigen to discriminate
      latent from active infection. METHODOLOGY AND PRINCIPAL FINDINGS: We performed a
      pilot investigation to study humoral and T-cell mediated immunological responses
      to recombinant HBHA produced in M. smegmatis or to synthetic peptides in patients
      with recent or past tuberculosis, with atypical mycobacteriosis, or in healthy
      vaccinated individuals. The T cell reactivities to HBHA were compared to the
      respective reactivities towards Purified Protein Derivative (PPD) and two surface
      secreted proteins, ie. Early Secretory Antigen Target-6 (ESAT-6) and Culture
      Filtrate Protein-10 (CFP-10). Our pilot results indicate that methylated
      recombinant HBHA induced a strong T cell mediated immune response and the
      production of IgG and IgM-class antibodies in all patient groups, most
      surprisingly in young Finnish vaccinees, as well. We observed a positive
      correlation between the reactivities to HBHA and non-specific PPD among all
      studied subjects. As expected, ESAT-6 and CFP-10 were the most powerful antigens
      to discriminate disease from immunity caused by vaccination. CONCLUSIONS: On the
      basis of results of this exploratory investigation we raise concerns that in
      countries like Finland, where BCG vaccination was routinely used, HBHA utility
      might not be sufficient for diagnostics because of inability to explicitly
      discriminate tuberculosis infection from immunoreactivity caused by previous BCG
      vaccination.

PMID- 18815612
TI  - Genetic analysis of the role of protein kinase Ctheta in platelet function and
      thrombus formation.
AB  - BACKGROUND: PKCtheta is a novel protein kinase C isozyme, predominately expressed
      in T cells and platelets. PKCtheta(-/-) T cells exhibit reduced activation and
      PKCtheta(-/-) mice are resistant to autoimmune disease, making PKCtheta an
      attractive therapeutic target for immune modulation. Collagen is a major agonist
      for platelets, operating through an immunoreceptor-like signalling pathway from
      its receptor GPVI. Although it has recently been shown that PKCtheta positively
      regulates outside-in signalling through integrin alpha(IIb)beta(3) in platelets,
      the role of PKCtheta in GPVI-dependent signalling and functional activation of
      platelets has not been assessed. METHODOLOGY/PRINCIPAL FINDINGS: In the present
      study we assessed static adhesion, cell spreading, granule secretion, integrin
      alpha(IIb)beta(3) activation and platelet aggregation in washed mouse platelets
      lacking PKCtheta. Thrombus formation on a collagen-coated surface was assessed in
      vitro under flow. PKCtheta(-/-) platelets exhibited reduced static adhesion and
      filopodia generation on fibrinogen, suggesting that PKCtheta positively regulates
      outside-in signalling, in agreement with a previous report. In contrast,
      PKCtheta(-/-) platelets also exhibited markedly enhanced GPVI-dependent alpha
      granule secretion, although dense granule secretion was unaffected, suggesting
      that PKCtheta differentially regulates these two granules. Inside-out regulation
      of alpha(IIb)beta(3) activation was also enhanced downstream of GPVI stimulation.
      Although this did not result in increased aggregation, importantly thrombus
      formation on collagen under high shear (1000 s(-1)) was enhanced.
      CONCLUSIONS/SIGNIFICANCE: These data suggest that PKCtheta is an important
      negative regulator of thrombus formation on collagen, potentially mediated by
      alpha-granule secretion and alpha(IIb)beta(3) activation. PKCtheta therefore may
      act to restrict thrombus growth, a finding that has important implications for
      the development and safe clinical use of PKCtheta inhibitors.

PMID- 18815613
TI  - Species specificity in major urinary proteins by parallel evolution.
AB  - Species-specific chemosignals, pheromones, regulate social behaviors such as
      aggression, mating, pup-suckling, territory establishment, and dominance. The
      identity of these cues remains mostly undetermined and few mammalian pheromones
      have been identified. Genetically-encoded pheromones are expected to exhibit
      several different mechanisms for coding 1) diversity, to enable the signaling of
      multiple behaviors, 2) dynamic regulation, to indicate age and dominance, and 3)
      species-specificity. Recently, the major urinary proteins (Mups) have been shown
      to function themselves as genetically-encoded pheromones to regulate species
      specific behavior. Mups are multiple highly related proteins expressed in
      combinatorial patterns that differ between individuals, gender, and age; which
      are sufficient to fulfill the first two criteria. We have now characterized and
      fully annotated the mouse Mup gene content in detail. This has enabled us to
      further analyze the extent of Mup coding diversity and determine their potential
      to encode species-specific cues.Our results show that the mouse Mup gene cluster
      is composed of two subgroups: an older, more divergent class of genes and
      pseudogenes, and a second class with high sequence identity formed by recent
      sequential duplications of a single gene/pseudogene pair. Previous work suggests
      that truncated Mup pseudogenes may encode a family of functional hexapeptides
      with the potential for pheromone activity. Sequence comparison, however, reveals
      that they have limited coding potential. Similar analyses of nine other completed
      genomes find Mup gene expansions in divergent lineages, including those of rat,
      horse and grey mouse lemur, occurring independently from a single ancestral Mup
      present in other placental mammals. Our findings illustrate that increasing
      genomic complexity of the Mup gene family is not evolutionarily isolated, but is
      instead a recurring mechanism of generating coding diversity consistent with a
      species-specific function in mammals.

PMID- 18815614
TI  - Analysis of area-specific expression patterns of RORbeta, ER81 and Nurr1 mRNAs in
      rat neocortex by double in situ hybridization and cortical box method.
AB  - BACKGROUND: The mammalian neocortex is subdivided into many areas, each of which
      exhibits distinctive lamina architecture. To investigate such area differences in
      detail, we chose three genes for comparative analyses, namely, RORbeta, ER81 and
      Nurr1, mRNAs of which have been reported to be mainly expressed in layers 4, 5
      and 6, respectively. To analyze their qualitative and quantitative coexpression
      profiles in the rat neocortex, we used double in situ hybridization (ISH)
      histochemistry and cortical box method which we previously developed to integrate
      the data of different staining and individuals in a standard three-dimensional
      space. PRINCIPAL FINDINGS: Our new approach resulted in three main observations.
      First, the three genes showed unique area distribution patterns that are mostly
      complementary to one another. The patterns revealed by cortical box method
      matched well with the cytoarchitectonic areas defined by Nissl staining. Second,
      at single cell level, RORbeta and ER81 mRNAs were coexpressed in a subpopulation
      of layer 5 neurons, whereas Nurr1 and ER81 mRNAs were not colocalized. Third,
      principal component analysis showed that the order of hierarchical processing in
      the cortex correlates well with the expression profiles of these three genes.
      Based on this analysis, the dysgranular zone (DZ) in the somatosensory area was
      considered to exhibit a profile of a higher order area, which is consistent with
      previous proposal. CONCLUSIONS/SIGNIFICANCE: The tight relationship between the
      expression of the three layer specific genes and functional areas were revealed,
      demonstrating the usefulness of cortical box method in the study on the cerebral
      cortex. In particular, it allowed us to perform statistical evaluation and
      pattern matching, which would become important in interpreting the ever
      increasing data of gene expression in the cortex.

PMID- 18815615
TI  - Single-species microarrays and comparative transcriptomics.
AB  - BACKGROUND: Prefabricated expression microarrays are currently available for only
      a few species but methods have been proposed to extend their application to
      comparisons between divergent genomes. METHODOLOGY/PRINCIPAL FINDINGS: Here we
      demonstrate that the hybridization intensity of genomic DNA is a poor basis on
      which to select unbiased probes on Affymetrix expression arrays for studies of
      comparative transcriptomics, and that doing so produces spurious results. We used
      the Affymetrix Xenopus laevis microarray to evaluate expression divergence
      between X. laevis, X. borealis, and their F1 hybrids. When data are analyzed with
      probes that interrogate only sequences with confirmed identity in both species,
      we recover results that differ substantially analyses that use genomic DNA
      hybridizations to select probes. CONCLUSIONS/SIGNIFICANCE: Our findings have
      implications for the experimental design of comparative expression studies that
      use single-species microarrays, and for our understanding of divergent expression
      in hybrid clawed frogs. These findings also highlight important limitations of
      single-species microarrays for studies of comparative transcriptomics of
      polyploid species.

PMID- 18815616
TI  - Cross-Species Differential Plasma Protein Binding of MBX-102/JNJ39659100: A Novel
      PPAR-gamma Agonist.
AB  - Drug binding to plasma proteins restricts their free and active concentrations,
      thereby affecting their pharmacokinetic properties. Species differences in plasma
      protein levels complicate the understanding of interspecies pharmacodynamic and
      toxicological effects. MBX-102 acid/JNJ39659100 is a novel PPAR-gamma agonist in
      development for the treatment of type 2 diabetes. Studies were performed to
      evaluate plasma protein binding to MBX-102 acid and evaluate species differences
      in free drug levels. Equilibrium dialysis studies demonstrated that MBX-102 acid
      is highly bound (>98%) to human, rat and mouse albumin and that free MBX-102 acid
      levels are higher in rodent than in human plasma. Interspecies differences in
      free drug levels were further studied using PPAR-gamma transactivation assays and
      a newly developed PPAR-gamma corepressor displacement (biochemical) assay. PPAR
      gamma transactivation and corepressor displacement by MBX-102 acid was higher in
      rat and mouse serum than human serum. These results confirm the relevance of
      interspecies differences in free MBX-102 acid levels.

PMID- 18815617
TI  - Photodynamic therapy and the development of metal-based photosensitisers.
AB  - Photodynamic therapy (PDT) is a treatment modality that has been used in the
      successful treatment of a number of diseases and disorders, including age-related
      macular degeneration (AMD), psoriasis, and certain cancers. PDT uses a
      combination of a selectively localised light-sensitive drug (known as a
      photosensitiser) and light of an appropriate wavelength. The light-activated form
      of the drug reacts with molecular oxygen to produce reactive oxygen species (ROS)
      and radicals; in a biological environment these toxic species can interact with
      cellular constituents causing biochemical disruption to the cell. If the
      homeostasis of the cell is altered significantly then the cell enters the process
      of cell death. The first photosensitiser to gain regulatory approval for clinical
      PDT was Photofrin. Unfortunately, Photofrin has a number of associated
      disadvantages, particularly pro-longed patient photosensitivity. To try and
      overcome these disadvantages second and third generation photosensitisers have
      been developed and investigated. This Review highlights the key photosensitisers
      investigated, with particular attention paid to the metallated and non-metallated
      cyclic tetrapyrrolic derivatives that have been studied in vitro and in vivo;
      those which have entered clinical trials; and those that are currently in use in
      the clinic for PDT.

PMID- 18815618
TI  - Viral infection: a potent barrier to transplantation tolerance.
AB  - Transplantation of allogeneic organs has proven to be an effective therapeutic
      for a large variety of disease states, but the chronic immunosuppression that is
      required for organ allograft survival increases the risk for infection and
      neoplasia and has direct organ toxicity. The establishment of transplantation
      tolerance, which obviates the need for chronic immunosuppression, is the ultimate
      goal in the field of transplantation. Many experimental approaches have been
      developed in animal models that permit long-term allograft survival in the
      absence of chronic immunosuppression. These approaches function by inducing
      peripheral or central tolerance to the allograft. Emerging as some of the most
      promising approaches for the induction of tolerance are protocols based on
      costimulation blockade. However, as these protocols move into the clinic, there
      is recognition that little is known as to their safety and efficacy when
      confronted with environmental perturbants such as virus infection. In animal
      models, it has been reported that virus infection can prevent the induction of
      tolerance by costimulation blockade and, in at least one experimental protocol,
      can lead to significant morbidity and mortality. In this review, we discuss how
      viruses modulate the induction and maintenance of transplantation tolerance.

PMID- 18815619
TI  - PPAR Gamma Activators: Off-Target Against Glioma Cell Migration and Brain
      Invasion.
AB  - Today, there is increasing evidence that PPARgamma agonists, including
      thiazolidinediones (TDZs) and nonthiazolidinediones, block the motility and
      invasiveness of glioma cells and other highly migratory tumor entities. However,
      the mechanism(s) by which PPARgamma activators mediate their antimigratory and
      anti-invasive properties remains elusive. This letter gives a short review on the
      debate and adds to the current knowledge by applying a PPARgamma inactive
      derivative of the TDZ troglitazone (Rezulin) which potently counteracts
      experimental glioma progression in a PPARgamma independent manner.

PMID- 18815620
TI  - Regulation of Cell Proliferation and Differentiation by PPARbeta/delta.
AB  - Peroxisome proliferator-activated receptor-beta/delta (PPARbeta/delta) is a
      ligand-activated transcription factor with essential functions in the regulation
      of lipid catabolism, glucose homeostasis, and inflammation, which makes it a
      potentially relevant drug target for the treatment of major human diseases. In
      addition, there is strong evidence that PPARbeta/delta modulates oncogenic
      signaling pathways and tumor growth. Consistent with these observations, numerous
      reports have clearly documented a role for PPARbeta/delta in cell cycle control,
      differentiation, and apoptosis. However, the precise role of PPARbeta/delta in
      tumorigenesis and cell proliferation remains controversial. This review
      summarizes our current knowledge and proposes a model corroborating the
      discrepant data in this area of research.

PMID- 18815621
TI  - In situ observation of modulated light emission of fiber fuse synchronized with
      void train over hetero-core splice point.
AB  - BACKGROUND: Fiber fuse is a process of optical fiber destruction under the action
      of laser radiation, found 20 years ago. Once initiated, opical discharge runs
      along the fiber core region to the light source and leaves periodic voids whose
      shape looks like a bullet pointing the direction of laser beam. The relation
      between damage pattern and propagation mode of optical discharge is still unclear
      even after the first in situ observation three years ago. METHODOLOGY/PRINCIPAL
      FINDINGS: Fiber fuse propagation over hetero-core splice point (Corning SMF-28e
      and HI 1060) was observed in situ. Sequential photographs obtained at intervals
      of 2.78 micros recorded a periodic emission at the tail of an optical discharge
      pumped by 1070 nm and 9 W light. The signal stopped when the discharge ran over
      the splice point. The corresponding damage pattern left in the fiber core region
      included a segment free of periodicity. CONCLUSIONS: The spatial modulation
      pattern of the light emission agreed with the void train formed over the hetero
      core splice point. Some segments included a bullet-shaped void pointing in the
      opposite direction to the laser beam propagation although the sequential
      photographs did not reveal any directional change in the optical discharge
      propagation.

PMID- 18815622
TI  - A functionalized poly(ethylene glycol)-based bioassay surface chemistry that
      facilitates bio-immobilization and inhibits non-specific protein, bacterial, and
      mammalian cell adhesion.
AB  - This paper describes a new bioassay surface chemistry that effectively inhibits
      non-specific biomolecular and cell binding interactions, while providing a
      capacity for specific immobilization of desired biomolecules. Poly(ethylene
      glycol) (PEG) as the primary component in nonfouling film chemistry is well
      established, but the multicomponent formulation described here is unique in that
      it (1) is applied in a single, reproducible, solution-based coating step; (2) can
      be applied to diverse substrate materials without the use of special primers; and
      (3) is readily functionalized to provide specific attachment chemistries. Surface
      analysis data are presented, detailing surface roughness, polymer film thickness,
      and film chemistry. Protein non-specific binding assays demonstrate significant
      inhibition of serum, fibrinogen, and lysozyme adsorption to coated glass, indium
      tin oxide, and tissue culture polystyrene dishes. Inhibition of S. aureus and K.
      pneumoniae microbial adhesion in a microfluidic flow cell, and inhibition of
      fibroblast cell adhesion from serum-based cell culture is shown. Effective
      functionalization of the coating is demonstrated by directing fibroblast adhesion
      to polymer surfaces activated with an RGD peptide. Batch-to-batch reproducibility
      data are included. The in situ cross-linked PEG-based coating chemistry is unique
      in its formulation, and its surface properties are attractive for a broad range
      of in vitro bioassay applications.

PMID- 18815623
TI  - Beyond the Gene Chip.
AB  - We describe a prospective strategy for reading the encyclopedic information
      encoded in the genome: using a nanopore in a membrane formed from an MOS
      capacitor to sense the charge in DNA. In principle, as DNA permeates the
      capacitor-membrane through the pore, the electrostatic charge distribution
      characteristic of the molecule should polarize the capacitor and induce a voltage
      on the electrodes that can be measured. Silicon nanofabrication and molecular
      dynamic simulations with atomic detail are technological linchpins in the
      development of this detector. The sub-nanometer precision available through
      silicon nanotechnology facilitates the fabrication of the detector, and molecular
      dynamics provides us with a means to design it and analyze the experimental
      outcomes.

PMID- 18815624
TI  - Intermittent child employment and its implications for estimates of child labour.
AB  - Using longitudinal data from urban Brazil, the authors track the employment
      patterns of thousands of children aged 10-16 during four months of their lives in
      the 1980s and 1990s. The proportion of children who work at some point during a
      four-month period is substantially higher than the fraction observed working in
      any single month. The authors calculate an intermittency multiplier to summarize
      the difference between employment rates in one reference week vs. four reference
      weeks over a four-month period. They conclude that intermittent employment is a
      crucial characteristic of child labour which must be recognized to capture levels
      of child employment adequately and identify child workers.

PMID- 18815625
TI  - LINKING POVERTY AND INCOME SHOCKS TO RISKY SEXUAL BEHAVIOUR: EVIDENCE FROM A
      PANEL STUDY OF YOUNG ADULTS IN CAPE TOWN.
AB  - Is there a link between household income and income stress, and risky sexual
      behaviour of young people? Anecdotal and qualitative evidence suggests this may
      be the case, but there is little quantitative research measuring this
      relationship. We use two waves of new data from the Cape Area Panel Study to
      investigate this link for 2,993 African and coloured youths aged 14 to 22 in
      2002. In the process, we discuss one type of research design that could allow for
      a causal interpretation of the effect of income poverty on HIV risk. This design
      plausibly separates out the effect of income stress from the effect of living in
      a poor household by comparing behaviours across households with and without
      negative economic shocks, conditional on baseline income. Our results indicate
      that females in poorer households are more likely to be sexually active in 2002
      and more likely to sexually debut by 2005. In addition, girls in households
      experiencing negative economic shocks are more likely to reduce condom use
      between 2002 and 2005. However, they are less likely to have multiple partners in
      2002 or have transitioned to multiple partners by 2005. Males who experienced a
      negative shock are more likely to have multiple partners. Despite the tight
      research design for assessing shocks, the findings on the impacts of shocks do
      not generate clear recommendations for policy. There appears to be no systematic
      difference in condom use at last sex by household income levels or income shocks.

PMID- 18815626
TI  - The sensitivity to key data imputations of recent estimates of income poverty and
      inequality in South Africa.
AB  - Existing literature using South African censuses reports an increase in both
      poverty and inequality over the 1996 to 2001 period. This paper assesses the
      robustness of these results to a number of weaknesses in the personal income
      variable. We use a sequential regression multiple imputation approach to impute
      missing values and to explicitly assess the influence of implausible income
      values and different rules used to convert income that is measured in bands into
      point incomes. Overall our results for 1996 and 2001 confirm the major findings
      from the existing literature while generating more reliable confidence intervals
      for the key parameters of interest than are available elsewhere.

PMID- 18815627
TI  - Intensive Intervention for Students with Mathematics Disabilities: Seven
      Principles of Effective Practice.
AB  - The focus of this article is intervention for third - grade students with serious
      mathematics deficits at third grade. In third grade, such deficits are clearly
      established, and identification of mathematics disabilities typically begins. We
      provide background information on two aspects of mathematical cognition that
      present major challenges for students in the primary grades: number combinations
      and story problems. We then focus on seven principles of effective intervention.
      First, we describe a validated, intensive remedial intervention for number
      combinations and another for story problems. Then, we use these interventions to
      illustrate the first six principles for designing intensive tutoring protocols
      for students with mathematics disabilities. Next, using the same validated
      interventions, we report the percentage of students whose learning outcomes were
      inadequate despite the overall efficacy of the interventions and explain how
      ongoing progress monitoring represents a seventh, and perhaps the most essential,
      principle of intensive intervention. We conclude by identifying issues and
      directions for future research in the primary and later grades.

PMID- 18815628
TI  - Comparative study of regulatory T cell function of human CD25CD4 T cells from
      thymocytes, cord blood, and adult peripheral blood.
AB  - CD25(+)CD4(+) regulatory T cells suppress T cell activation and regulate multiple
      immune reactions in in vitro and in vivo studies. To define the regulatory
      function of human CD25(+)CD4(+) T cells at various stages of maturity, we
      investigated in detail the functional differences of CD25(+)CD4(+) T cells from
      thymocytes, cord blood (CB), and adult peripheral blood (APB). CB CD25(+)CD4(+) T
      cells displayed low-FOXP3 protein expression level and had no suppressive
      activity. In contrast, CD25(+)CD4(+) T cells from thymocytes or APB expressed
      high expression level of FOXP3 protein associated with significant suppressive
      activity. Although CB CD25(+)CD4(+) T cells exhibited no suppressive activity,
      striking suppressive activity was observed following expansion in culture
      associated with increased FOXP3 expression and a shift from the CD45RA(+) to the
      CD45RA(-) phenotype. These functional differences in CD25(+)CD4(+) T cells from
      Thy, CB, and APB hence suggest a pathway of maturation for Treg in the peripheral
      immune system.

PMID- 18815629
TI  - Tandemly arrayed genes in vertebrate genomes.
AB  - Tandemly arrayed genes (TAGs) are duplicated genes that are linked as neighbors
      on a chromosome, many of which have important physiological and biochemical
      functions. Here we performed a survey of these genes in 11 available vertebrate
      genomes. TAGs account for an average of about 14% of all genes in these
      vertebrate genomes, and about 25% of all duplications. The majority of TAGs (72
      94%) have parallel transcription orientation (i.e., they are encoded on the same
      strand) in contrast to the genome, which has about 50% of its genes in parallel
      transcription orientation. The majority of tandem arrays have only two members.
      In all species, the proportion of genes that belong to TAGs tends to be higher in
      large gene families than in small ones; together with our recent finding that
      tandem duplication played a more important role than retroposition in large
      families, this fact suggests that among all types of duplication mechanisms,
      tandem duplication is the predominant mechanism of duplication, especially in
      large families. Finally, several species have a higher proportion of large tandem
      arrays that are species-specific than random expectation.

PMID- 18815630
TI  - Peroxisome Proliferator-Activated Receptor Delta: A Conserved Director of Lipid
      Homeostasis through Regulation of the Oxidative Capacity of Muscle.
AB  - The peroxisome proliferator-activated receptors (PPARs), which are ligand
      inducible transcription factors expressed in a variety of tissues, have been
      shown to perform key roles in lipid homeostasis. In physiological situations such
      as fasting and physical exercise, one PPAR subtype, PPARdelta, triggers a
      transcriptional program in skeletal muscle leading to a switch in fuel usage from
      glucose/fatty acids to solely fatty acids, thereby drastically increasing its
      oxidative capacity. The metabolic action of PPARdelta has also been verified in
      humans. In addition, it has become clear that the action of PPARdelta is not
      restricted to skeletal muscle. Indeed, PPARdelta has been shown to play a crucial
      role in whole-body lipid homeostasis as well as in insulin sensitivity, and it is
      active not only in skeletal muscle (as an activator of fat burning) but also in
      the liver (where it can activate glycolysis/lipogenesis, with the produced fat
      being oxidized in muscle) and in the adipose tissue (by incrementing lipolysis).
      The main aim of this review is to highlight the central role for activated
      PPARdelta in the reversal of any tendency toward the development of insulin
      resistance.

PMID- 18815631
TI  - Acute abdomen in an asbestos factory worker.

PMID- 18815632
TI  - Burkitt's lymphoma of the ileum with renal cell carcinoma.

PMID- 18815633
TI  - Giant retroperitoneal sarcoma.

PMID- 18815634
TI  - Hepatic artery aneurysm secondary to epithelioid angiosarcoma.

PMID- 18815635
TI  - Jejunojejunal intussusception by a known jejunal adenocarcinoma.

PMID- 18815636
TI  - Primary squamous cell carcinoma of the main hepatic bile duct.

PMID- 18815637
TI  - Radiolucent foreign body visible on plain radiography.

PMID- 18815638
TI  - Supradiaphragmatic perforated duodenal ulcer in a giant hiatus hernia.

PMID- 18815639
TI  - Aortic arch aneurysm rupture into the lung misdiagnosed as lung carcinoma.

PMID- 18815640
TI  - Robot-assisted minimally invasive common bile duct exploration: a Canadian first.

PMID- 18815641
TI  - Spontaneous bilateral fracture of the proximal humerus: an unusual presentation
      of multiple myeloma.

PMID- 18815642
TI  - Giant left atrial myxoma causing mitral valve obstruction and pulmonary
      hypertension.

PMID- 18815643
TI  - Broadening the mandate for international surgery.

PMID- 18815644
TI  - Surgeons and astronauts: so close, yet so far apart.

PMID- 18815645
TI  - International surgery and the Canadian Journal of Surgery.

PMID- 18815646
TI  - Prognostic variables in adult Wilms tumour.
AB  - OBJECTIVE: To identify outcomes and prognostic variables that predict survival
      outcomes in adult Wilms tumour patients. METHODS: We collected data on 128
      patients with adult Wilms tumour treated between 1973 and 2006. Six cases from
      our 2 Canadian centres have not been previously reported. We collected data on
      the remaining 122 patients from published case reports or case series. Analyzed
      factors included age, sex, favourable or unfavourable histopathology, clinical
      stage (I, II, III or IV) and chemotherapy and radiotherapy received. The outcomes
      studied included overall survival (OS) and disease-specific survival (DSS).
      Univariate analysis with Kaplan-Meier actuarial methodology and multivariate
      analyses with Cox regression were used to determine outcomes and predictive
      clinical factors. RESULTS: The patients' mean age was 26 (range 15-73) years.
      After a mean follow-up of 54 (range 2-240) months, the OS and DSS of the entire
      cohort were both 68%. Favourable histopathology predicted superior OS and DSS
      (both p < 0.001). Higher clinical stage predicted inferior OS and DSS (both p <
      0.001). CONCLUSION: Adult Wilms tumour has a poorer prognosis than pediatric
      Wilms tumour. In adults with Wilms tumour, more aggressive patient-and tumour
      specific surveillance and adjunctive therapies than those advocated by pediatric
      National Wilms Tumor Study guidelines may be warranted, especially in patients
      with an unfavourable histopathology and higher clinical stage.

PMID- 18815647
TI  - Ten-year follow-up of a province-wide cohort of surgical lung cancer patients in
      Nova Scotia.
AB  - BACKGROUND: After a diagnosis of lung carcinoma, survival is poor for all
      patients. We sought to assess 10-year survival and predictors of outcome after
      surgery for lung cancer in Nova Scotia. METHODS: We identified all patients n =
      130) undergoing resection for lung cancer in Nova Scotia in 1994 from the Nova
      Scotia Cancer Registry and hospital charts and followed them prospectively for 10
      years. We used Cox proportional hazards modelling to identify predictors of
      survival. RESULTS: The patients' mean age at operation was 67.7 (standard
      deviation [SD] 8.2) years, and 70% of the patients were men. Most of the
      operations n = 80, 61.5%) were performed in Halifax, and adenocarcinoma n = 55,
      42.3%) was the most common histologic type. At the time of surgery, 66.9% of the
      cases were stage 1, 20.0% were stage 2 and 13.1% were stage 3. Survival at 5 and
      10 years was 34% and 13%, respectively. Age of 70 years or older (hazard ratio
      [HR] 1.79, 95% confidence interval [CI] 1.20-2.68), large cell carcinoma (HR
      2.27, 95% CI 1.31-3.94) and stage 3 cancer (HR 2.21, 95% CI 1.25-3.90) were
      significant independent predictors of survival. Hospital site was not associated
      with any difference in survival (p = 0.66), although there was a trend toward
      differential rates of lymph node sampling across sites (p = 0.06). The presence
      of node sampling was associated with improved survival in a separate multivariate
      model (HR 0.51, 95% CI 0.29-0.89). CONCLUSION: Actuarial survival after resection
      of lung carcinoma in Nova Scotia in 1994 was 34% at 5 years and 13% after 10
      years. Age, stage and histology are independent predictors of survival; lymph
      node sampling was associated with greater survival.

PMID- 18815648
TI  - Hardware removal after tibial fracture has healed.
AB  - BACKGROUND: Tibial fractures are the most common long bone fracture. The standard
      of care for the treatment of diaphyseal tibial fractures is an intramedullary
      nail (IMN). Implant removal is one of the most common procedures in bone and
      joint surgery, and criteria for implant removal are typically left to the
      treating surgeon. Currently, no clear criteria exist to guide a surgeon's
      decision to remove implanted tibial IMNs after healing. METHODS: We undertook a
      retrospective chart review of a single surgeon's practice from January 1996 to
      February 2005. We identified patients aged 16-70 years with a tibial fracture
      treated with an IMN. Patients were followed until fracture union and/or request
      for IMN removal. The following parameters were recorded: reason for implant
      removal, age, sex, mechanism of fracture, location of fracture, diameter of IMN,
      Workers' Compensation Board (WCB) status, activity level, litigation status,
      insurance involvement, height, weight and body mass index (BMI). RESULTS: Factors
      influencing the likelihood of removal were sex and litigation. Factors not
      influencing the likelihood of removal were age, weight, height, BMI, diameter of
      IMN, patients' level of activity, insurance claim involvement and WCB
      involvement. Overall, 72.2% of patients had an improvement in their symptoms
      after IMN removal. CONCLUSION: Sex and litigation are positive predictive factors
      for patient requests to have tibial IMNs removed after healing.

PMID- 18815649
TI  - Autologous bone marrow cell transplantation combined with off-pump coronary
      artery bypass grafting in patients with ischemic cardiomyopathy.
AB  - BACKGROUND: Clinical studies have demonstrated that intracoronary or
      intramyocardial transplantation of bone marrow mononuclear cells (BMMNCs) into
      ischemic myocardium improves cardiac function. The objective of the present study
      was to evaluate the safety and feasibility of intramyocardial BMMNC
      transplantation into nongraftable areas in combination with off-pump coronary
      artery bypass grafting in patients with ischemic cardiomyopathy. METHODS: Five
      male patients with myocardial infarction lasting for more than 1 month and with
      nongraftable myocardium received autologous mononuclear cell transplantation
      during off-pump coronary artery bypass grafting. Autologous bone marrow was
      aspirated from the iliac crest. BMMNCs (mean 1.6, standard error [SE] 0.3 x
      10(9)) including CD34-positive cells (mean 6.8, SE 1.1 x 10(6)) and AC133
      positive cells (mean 3.1, SE 1.7 x 10(6)) were injected into the nongraftable
      ischemic myocardium. Heart function was evaluated with the use of
      echocardiography, and myocardial perfusion was examined with single photon
      emission computed tomography technetium-99mTc sestamibi scans. RESULTS: Two
      months after cell transplantation, the mean ejection fraction had increased by
      7.4%, SE 1.9% (p = 0.016) compared with that before cell transplantation and off
      pump coronary artery bypass grafting. The increase in ejection fraction was not
      correlated with the number of transplanted total mononuclear cells, CD34-positive
      cells and AC133-positive cells. Myocardial perfusion at the cell-transplanted
      area increased after cell transplantation and off-pump coronary artery bypass
      grafting. No arrhythmia was observed. CONCLUSION: The present clinical study
      suggests that intramyocardial transplantation of autologous BMMNCs into the
      ischemic area during off-pump coronary artery bypass grafting is both feasible
      and safe and has beneficial effects on cardiac function.

PMID- 18815650
TI  - Laparoscopic compared with open adrenalectomy for resection of pheochromocytoma:
      a review of 47 cases.
AB  - OBJECTIVE: We conducted a retrospective cohort study to determine whether
      laparoscopic adrenalectomy (LA) is a safe and effective therapy for the
      management of pheochromocytoma, as compared with open adrenalectomy (OA).
      METHODS: We collected pertinent data on 47 pheochromocytoma resections from 44
      patient charts. Perioperative outcomes of 30 LAs were compared with 14 OAs.
      RESULTS: Median (and standard deviation [SD]) length of postoperative stay was
      shorter in the laparoscopic group (3.0, SD 3.3 d v. 6.0, SD 1.1 d; p < 0.05), and
      tumour size was smaller (3.9, SD 2.7 cm v. 5.0, SD 2.9 cm; p < 0.05). No
      statistically significant differences were found for operative time or rate of
      postoperative complications. There were no statistically significant between
      group differences in intraoperative hypertensive episodes (systolic blood
      pressure > 180 and/or diastolic blood pressure > 90) or hypotensive episodes
      (systolic blood pressure < 100 and/or diastolic blood pressure < 60) or in the
      need for antihypertensive or vasopressive agents. There were no intraoperative
      complications related to extremes of blood pressure. There were no perioperative
      mortalities in this series, nor was there an increased risk of recurrent disease
      with the laparoscopic technique. CONCLUSION: LA is safe and effective for the
      management of pheochromocytoma.

PMID- 18815651
TI  - Endoscopic plantar fasciotomy in the treatment of chronic heel pain.
AB  - OBJECTIVE: To evaluate endoscopic plantar fasciotomy for the treatment of
      recalcitrant heel pain. METHOD: We undertook a retrospective study of the use of
      endoscopic plantar fasciotomy in the treatment of chronic heel pain that was
      unresponsive to conservative treatment. Over a 10-year period, we reviewed the
      charts of 55 patients with a minimum 12-month history of heel pain that failed to
      respond to standard nonoperative methods and had undergone the procedure
      described. All patients were clinically reviewed and completed a questionnaire
      based on the American Orthopaedic Foot and Ankle Society (AOFAS) score for ankle
      and hindfoot. RESULTS: The mean follow-up was 18 months. The mean preoperative
      AOFAS score was 66.5; the mean postoperative AOFAS score was 88.2. The mean
      preoperative pain score was 18.6; the mean postoperative pain score was 31.1.
      Complications were minimal (2 superficial wound infections). Overall, results
      were favourable in over 80% of patients. CONCLUSION: We conclude that endoscopic
      plantar fasciotomy is a reasonable option in the treatment of chronic heel pain
      that fails to respond to a trial of conservative treatment.

PMID- 18815652
TI  - Pathological reporting of colorectal cancer specimens: a retrospective survey in
      an academic Canadian pathology department.
AB  - OBJECTIVE: To survey and improve the pathological reporting of colorectal cancer
      (CRC) specimens in a tertiary care pathology department. METHODS: We identified
      CRC specimens reported in a 6-month period before and after educational sessions
      and the introduction of a standardized CRC synoptic reporting protocol. Gross and
      microscopic descriptions were analyzed according to published guidelines for
      important staging and prognostic features. We then reexamined these parameters
      for a further 6-month period 15 months later to ensure that the quality of
      reporting had been maintained. RESULTS: In total, 108 and 166 cases were analyzed
      before and after standardization, respectively. Many features were reported
      appropriately, including tumour size, type and grade, depth of invasion, nodal
      status and proximal and distal margin status. Several underreported features
      showed significant improvement after standardization, including serosal
      involvement (reporting increased from 22% to 84%), distance to radial margin
      (from 14% to 64%), extramural venous invasion (from 18% to 88%), host response
      (from 19% to 94%) and mean number of nodes retrieved (mean numbers retrieved
      increased from 11 to 16). The subsequent review 15 months later showed continued
      long-term improvement in these areas. CONCLUSION: Education and synoptic
      reporting significantly improved CRC reporting at our centre.

PMID- 18815653
TI  - Using CanMEDS to guide international health electives: an enriching experience in
      Uganda defined for a Canadian surgery resident.
AB  - BACKGROUND: Surgery residents who wish to travel during their residency will
      often seek an elective experience in a low-or middle-income country. Objectives
      for international health electives (IHEs) are often vague and poorly defined.
      Further, feedback to, and evaluation of, the resident after the IHE are often not
      specific because international preceptors are not familiar with the desired
      educational outcomes of Canadian residency programs. Residents who choose an
      elective in a low-income country usually anticipate that they will contribute
      some medical service to an existing impoverished health care system, and in this
      setting, they hope to gain exposure to a high operative volume with potentially
      fewer institutional and administrative obstacles. METHODS: In this paper, we
      describe one resident's elective experience in Mbarara, Uganda. In addition to
      her clinical experience, the resident performed a retrospective audit of surgical
      admissions. After her elective, we asked the resident to reflect on her
      experience and to use the Canadian Medical Education Directives for Specialists
      (CanMEDS) framework to describe the challenges she encountered and to define the
      learning outcomes gained with respect to each CanMEDS role. RESULTS: We
      discovered that the resident had a rich and insightful educational experience
      when discussed in this context. As a result, we have created a guide for
      structuring postgraduate IHEs around the CanMEDS roles, using them to ask pre-and
      postelective questions to develop relevant and practical IHE objectives.
      CONCLUSION: We propose that this guide has the potential to improve both resident
      preparation before international experience and also subsequent evaluation of
      resident performance in this ill-defined area. More important, we found that IHEs
      are a useful vehicle to evaluate resident achievement of the CanMEDS competencies
      in a way that is reflective, realistic and representative of the multiple
      challenges involved when working in international health.

PMID- 18815654
TI  - CUSUM analysis of J-pouch surgery reflects no learning curve after board
      certification.
AB  - OBJECTIVE: To investigate changes in morbidity and mortality associated with
      ileal J-pouch surgery performed during the first 3 years of a single surgeon's
      practice to determine the presence or absence of a learning curve after
      fellowship training. METHODS: From July 2002 to July 2005, an observational study
      of postoperative outcomes was undertaken, in which 30-day and inhospital
      morbidity and mortality were assessed. A total of 37 patients (17 women and 20
      men) underwent the surgery; their average age was 32 (range 16-51) years. The
      operation was performed for ulcerative colitis n = 31), familial adenomatous
      polyposis n = 4) and indeterminate colitis n = 2); 32 were diverted and 5 were
      not. Predicted morbidity and mortality were 31.66% and 1.47%, respectively.
      Observed morbidity and mortality were 29.7% and 0%, respectively. I used a risk
      adjusted cumulative sum (CUSUM) model to compare observed outcomes with predicted
      outcomes according to a validated scoring system and to analyze outcomes with
      adjusting for risk on a case-by-case basis. RESULTS: CUSUM analysis revealed a
      flat curve trending down over the duration. CONCLUSION: CUSUM methodology permits
      documentation of quality control during the first 3 years of practice. The
      experience of a single board-certified colorectal surgeon reveals acceptable
      results in the first 3 years of practice, with no obvious learning curve. The
      results suggest that fellowship training and board certification conferred
      reasonable proficiency in J-pouch surgery before the onset of practice.

PMID- 18815657
TI  - Safety and efficiency of left hemihepatectomy combined with hepatic artery
      resection for hilar cholangiocarcinoma with artery infiltration: report of 2
      cases.

PMID- 18815660
TI  - The computerized tomography scans and their dosimetric safety.
AB  - In recent years, the volume of diagnostic procedures involving the use of
      ionizing radiation has rapidly increased. Technological advances in computed
      tomography (CT) equipment, with the availability of multi-slice acquisition and
      the introduction of hybrid systems, have made this modality extremely popular
      among other diagnostic procedures, especially in pediatrics and as a screening
      procedure for asymptomatic adults. Physicians' major radiation-related concern
      regarding diagnostic imaging, is possible iatrogenic malignancy. According to
      major national and international organizations responsible for evaluating
      radiation risks, there is no low-radiation threshold for inducing cancer. This
      means that no amount of radiation should be considered absolutely safe. Although,
      the risk of radiation-induced cancer is much smaller than the risk of cancer from
      natural sources, it can become a public health concern if large numbers of the
      population undergo increased numbers of CT screening procedures that may even be
      of uncertain benefit. In order to reduce the overall radiation dose from CT
      procedures in the population, it is important to keep radiation dose as low as
      reasonably achievable, by adjusting scanner parameters separately for each
      individual. In addition, it is crucial to eliminate the inappropriate referrals
      for CT tests and choose other diagnostic modalities, such as sonography, magnetic
      resonance imaging systems, or nuclear medicine procedures. While CT remains an
      important diagnostic procedure, it is important for health care community to
      reconsider the indications of a CT scan, especially in children and asymptomatic
      patients. Physicians who prescribe CT could assess its use on a case-by-case
      basis. When used prudently and optimally, CT remains a very valuable imaging
      modalitiy for both children and adults.

PMID- 18815661
TI  - Recent international regulations: low dose-low rate radiation protection and the
      demise of reason.
AB  - The radiation protection measures suggested by the International Committee for
      Radiation Protection (ICRP), national regulating bodies and experts, have been
      becoming ever more strict despite the decrease of any information supporting the
      existence of the Linear no Threshold model (LNT) and of any adverse effects of
      Low Dose Low Rate (LDLR) irradiation. This tendency arises from the
      disproportionate response of human society to hazards that are currently in
      fashion and is unreasonable. The 1 mSv/year dose limit for the public suggested
      by the ICRP corresponds to a 1/18,181 detriment-adjusted cancer risk and is much
      lower than other hazards that are faced by modern societies such as e.g. driving
      and smoking which carry corresponding rate risks of 1/2,100 and 1/2,000. Even
      worldwide deadly work accidents rate is higher at 1/ 8,065. Such excessive safety
      measures against minimal risks from man made radiation sources divert resources
      from very real and much greater hazards. In addition they undermine research and
      development of radiation technology and tend to subjugate science and the quest
      for understanding nature to phobic practices.

PMID- 18815662
TI  - Preparation and pharmacological evaluation of a new radiopharmaceutical,
      technetium-99m-5-fluorouracil, for tumor scintigraphy.
AB  - 5-fluorouracil (5-FU) has been used for cancer chemotherapy since more than four
      decades. There are reports of use of (18)F and (19)F analogues of 5-FU for tumor
      studies using PET and NMR respectively. However, study pertaining to its use in g
      scintigraphy is still lacking. In the present study, we have optimized the
      methodology to radiolabel it with technetium-99m ((99m)Tc) efficiently and
      evaluated its physicochemical and biological properties. METHODS: 5-FU was
      radiolabeled with (99m)Tc and evaluated for physicochemical properties. Blood
      kinetics were studied in rabbits and biodistribution was carried out in normal as
      well as tumor bearing mice. In vivo and in vitro tumor uptake of the radiocomplex
      was evaluated in Ehrlich Ascites Tumor (EAT) bearing mice and human breast cancer
      cell line (MDA-MB-468). RESULTS: The resultant radiopharmaceutical ((99m)Tc-5-FU)
      has been found to be stable up to 24 h in both in vitro normal and physiological
      conditions. The blood clearance of the (99m)Tc-5-FU showed a bi-phasic pattern.
      High extraction of (99m)Tc-5-FU by the liver (36.41+/-2.79% of injected dose/g
      tissue) has been observed in mice, along with time dependent increase in the
      solid tumor to muscle ratio (2:1) measured at 4 h. Incubation of the radiocomplex
      with human breast cancer cells lines also showed time dependent increase in the
      uptake of the tracer. CONCLUSION: It can be concluded that the (99m)Tc-5-FU
      possesses selectivity towards solid tumor tissue.

PMID- 18815663
TI  - Colonic transit studies with 99mTc-rhenium sulfide colloid in live rats. A
      preliminary study.
AB  - Abnormal colonic motility is associated with clinical relevant conditions such as
      irritable bowel syndrome or constipation. Accurate assessment of colonic transit
      in an animal model would be useful in studying these conditions and screen
      potential drug candidates. The aim of this study was to assess if scintigraphic
      analyses could reliably evaluate total and segmental colonic transit as a measure
      of colonic motility of a non-absorbable radiotracer in rats. Normal Lewis rats
      (250-300 g) were given oral technetium-99m-rhenium sulfide colloid (15-20 MBq;
      0.5 mL; n=4) followed by a rinse with water for injection (1.0 mL). Rats were fed
      and hydrated ad libitum. After 30 min, each rat was contained inside an 'imaging'
      tube then placed on a g-camera collimator. Whole body 5 min static images were
      acquired every 30 min up to 9 h, and then finally at 25 hours. Region of interest
      analyses were applied to the caecum/proximal colon, sigmoidal loop and distal
      colon/rectum. The tracer entered into the colon at approximately 4 hours, and the
      rats remained static to permit 'live' imaging. At 4 hours the % whole body
      activity was: 51% caecum/proximal colon, 39% sigmoidal loop, 6% distal
      colon/rectum; at 8 hours, 30% caecum/proximal colon, 13% sigmoidal loop, 7%
      distal colon/rectum. In the whole colon there was < or =1% of total activity
      present at 25 hours, and the half clearance time was determined as 4.0 hours.
      These results suggest this is a reliable technique of measuring regional colonic
      transit as a measure of colonic motility in normal rats. This methodology might
      be well suited to screen potential motility effects of drug candidates.

PMID- 18815664
TI  - A new approach for the development of tracers: data base screening and in silico
      modeling for the identification of new ligands for SSTR2.
AB  - New ligands are needed to improve diagnostics and treatment of SSTR2 expressing
      tumors. We implemented a procedure to identify ligands based on computer
      processing methods. A multistep procedure was used. Search entries were taken
      from National Cancer Institute database. Application of criteria defined by the
      Lipinski rules reduced the initial data set. Then a pharmacophore criterion
      including Lys and Trp residues was the next step of the hierarchical filtering,
      and the ligands considered were transformed from 2D to 3D. Finally, dedicated
      software was applied for docking ligand studies. Our results have shown that by
      virtual screening and trial docking, we identified novel ligands with better
      scores of docked poses compared with previously reported ligands. In conclusion,
      the use of a focused library that incorporates an initial probe, improved the
      possibility of a successful virtual screening as compared with random screening
      and is cost efficient by further combination of trial docking.

PMID- 18815665
TI  - Amiodaron treatment and thyroid autoimmunity markers.
AB  - Autoimmune diseases of the thyroid gland (ADTG) which include, Graves' disease,
      Hashimoto thyroiditis, primary hypothyroidism with atrophic thyroiditis,
      postpartum thyroiditis and 'silent' thyroiditis, are characterized by the
      presence of serum thyroid autoantibodies (TAB). Thyroid autoantibodies are not
      rare even in the general population of all ages, and their presence in women is 5
      times more than in men. The aim of our study was to define the prevalence of
      thyroid autoantibodies in patients on chronic treatment by amiodarone (AMD), an
      antiarrhythmic drug rich in iodine, with a potential cytotoxic effect. We have
      used a section study during a period of two years. Ninety six consecutive
      patients under AMD treatment were studied, 55 men and 41 women (mean age 62.2
      years, range 26-82 years) who referred to us to study their thyroid function. Our
      results showed that antithyroid antibodies in patients under AMD treatment, with
      or without thyroid dysfunction, were in similar concentrations as in the general
      population. A statistically significant greater frequency of increased thyroid
      peroxidase antibodies (TPOAb) was present in female patients under AMD treatment.
      When AMD treatment lasted longer than 24 months, the TPOAb were statically higher
      as compared to those patients under AMD treatment for less than 24 months.

PMID- 18815666
TI  - 99mTc-hexakis methoxy isobutyl isonitrile MIBI scintigraphy and bronchoalveolar
      fluid lactic dehydrogenase in pulmonary tuberculosis.
AB  - In cases of chronic pulmonary tuberculosis (PTB) with negative sputum smears,
      particularly when they are symptomatic, physicians encounter problems in
      differentiating the active from the inactive stage of the disease. This study was
      undertaken to determine the usefulness of technetium-99m hexakis methoxy isobutyl
      isonitrile ((99m)Tc-MIBI) pulmonary scintigraphy and lactic dehydrogenase (LDH)
      in bronchoalveolar lavage fluid (BALF), in differentiating active from inactive
      PTB. According to the methods we used, BALF LDH level was measured in 12 patients
      with documented active PTB (Group 1) before of treatment and in 7 patients with
      treated PTB (Group 2) after treatment. Lung scan with (99m)Tc-MIBI was performed
      in 7/12 patients of Group 1 (Group 1a) and in all of Group 2. Five patients of
      Group 1 refused the lung scan (Group 1b). Five adults who had a normal myocardial
      perfusion scan were considered as normal lung cases (Group 3). Our results showed
      that the mean LDH level in BALF was not statistically higher in Group 1 (252.42+/
      189.06 mIU/ml) than in Group 2 (106.28+/-139.99 mIU/ml). Very low values, less
      than 24 mIu/ml, excluded active PTB. Of the 7 patients of Group 1a, 6 had a
      positive lung scan (85.7%). Of the 7 patients of Group 2, 6 had negative lung
      scan (85.7%). Both tests had a positive correlation in differentiating active and
      inactive PTB. In conclusion, although none of the tests were specific for PTB,
      low BALF LDH of less than 24 mIUL and negative (99m)Tc-MIBI pulmonary
      scintigraphy, seemed to indicate inactive PTB. If our findings are confirmed by
      others with more related cases, these tests can be shown useful in the follow up
      of treated PTB patients.

PMID- 18815667
TI  - Brain scintigraphy with 99mTc-tetrofosmin for the differential diagnosis of a
      posterior fossa tumor.
AB  - A 60-year-old woman harbouring a tumour in the cerebellum. Anatomic brain imaging
      by computed tomography and magnetic resonance imaging were not conclusive of the
      lesion's nature. Imaging by (99m)Tc-tetrofosmin single-photon emission tomography
      (SPET) showed increased radiotracer accumulation in the lesion, indicating a
      vascular supply, membrane permeability and cellular metabolic activity, which is
      suggested to facilitate tracer uptake by lesions located in the posterior fossa.
      The patient underwent surgery and haemangioblastoma was confirmed by histology.
      Differential diagnosis is discussed. (99m)Tc-tetrofosmin scintiscan contributed
      to diagnostic information.

PMID- 18815668
TI  - Sporadic differentiated thyroid carcinoma in a 3 years old child.

PMID- 18815670
TI  - Atypical subacute thyroiditis causing fever of unknown origin: the value of
      gallium-67 imaging.

PMID- 18815671
TI  - Anticancer effects on leiomyosarcoma-bearing Wistar rats after electromagnetic
      radiation of resonant radiofrequencies.

PMID- 18815672
TI  - Anticancer effects on leiomyosarcoma-bearing Wistar rats after electromagnetic
      radiation of resonant radiofrequencies.

PMID- 18815673
TI  - Anticancer effects on leiomyosarcoma-bearing Wistar rats after electromagnetic
      radiation of resonant radiofrequencies.

PMID- 18815675
TI  - 99mTc-hexakis methoxy isobutyl isonitrile uptake patterns in nursing mothers and
      related dosimetry.

PMID- 18815676
TI  - A typical (111)In-diaethylenotriamino pentaacetic acid-octreotide and (99m)Tc-(V)
      dimercapto succinic acid uptake patterns, after radiation treatment.

PMID- 18815677
TI  - (18)F-FDG uptake in undescended testis mimicking inguinal adenopathy in a case of
      melanoma.

PMID- 18815678
TI  - Synthetic indole, carbazole, biindole and indolocarbazole-based receptors:
      applications in anion complexation and sensing.
AB  - Indole, biindole, carbazole and indolocarbazole-based receptors are rapidly
      emerging as an important new class of anion-binding agents. This Feature Article
      provides a comprehensive overview of the molecular recognition and structural
      chemistry of these neutral, yet highly effective, anion receptors and sensors.

PMID- 18815679
TI  - Heterocalixaromatics, new generation macrocyclic host molecules in supramolecular
      chemistry.
AB  - Heterocalixaromatics, the heteroatom bridged calix(hetero)arenes, have been
      emerging as new generation macrocyclic host molecules in supramolecular chemistry
      recently. Being different from the conventional calixarenes in which the aromatic
      rings are linked by methylene units, heterocalixaromatics assemble various
      aromatic rings by different heteroatoms. Owning to the intrinsic nature of
      heteroatoms that can adopt different electronic configurations to form various
      degrees of conjugation with their neighboring aromatic rings,
      heterocalixaromatics exhibit unique structural features and versatile recognition
      properties in comparison to conventional calixarenes. This feature article
      highlights recent advances in the synthesis, functionalization, structure and
      molecular recognition of nitrogen- and/or oxygen-bridged calixaromatics, with a
      primary focus on our own work.

PMID- 18815680
TI  - Structural studies in aqueous solution of new binuclear lanthanide luminescent
      peptide conjugates.
AB  - The synthesis, NMR and luminescent analysis of a novel polypeptide possessing a
      sensitising naphthalimide antenna at the amino terminus, and a model compound
      with a Trp moiety, and their Eu(iii) and Tb(iii) complexes are described.

PMID- 18815681
TI  - An aromatic coupling motif for two-dimensional supramolecular architectures.
AB  - We show, using scanning tunneling microscopy, how a coupling motif based on self
      complementary helical aromatic units is able to drive the formation of a chiral
      porous supramolecular network and chains based on lateral aromatic interactions
      in two dimensions.

PMID- 18815682
TI  - Modular construction of a series of heteronuclear metallamacrocycles.
AB  - High modularity in a series of heteronuclear d(8)-d(10) metallamacrocycles built
      on differentiated ligands is demonstrated.

PMID- 18815683
TI  - An interdigitated functionally rigid [2]rotaxane.
AB  - The synthesis of a functionally rigid [2]rotaxane incorporating pi-electron rich
      1,5-disubstituted naphthalene (NP) ring systems, encircled by the pi-electron
      deficient tetracationic cyclophane, cyclobis(paraquat-p-phenylene), is described;
      in the solid state, the molecules of this donor-acceptor [2]rotaxane line
      themselves up in parallel pi-pi stacks of alternating NP ring systems and
      bipyridinium units, affording an interdigitated superstructure.

PMID- 18815684
TI  - Bis(benzimidazole)pyridine derivative as a new class of G-quadruplex inducing and
      stabilizing ligand.
AB  - Two new bis(benzimidazole)aryl derivatives have been prepared and one of them has
      been shown to induce and stabilize formation of a G-quadruplex.

PMID- 18815685
TI  - Weighting non-covalent forces in the molecular recognition of C(60). Relevance of
      concave-convex complementarity.
AB  - The relative contributions of several weak intermolecular forces to the overall
      stability of the complexes formed between structurally related receptors and
      [60]fullerene are compared, revealing a discernible contribution from concave
      convex complementarity.

PMID- 18815686
TI  - Surface binding vs. sequestration; the uptake of benzohydroxamic acid at
      iron(iii) oxide surfaces.
AB  - Benzohydroxamic acid is shown to be an unexpectedly good ligand for iron(iii)
      oxides, favouring surface attachment to the formation of trisbenzohydroxamato
      complexes, which are known to have very high thermodynamic stability in solution.

PMID- 18815687
TI  - Detection of mismatched DNAs via the binding affinity of MutS using a gold
      nanoparticle-based competitive colorimetric method.
AB  - A gold nanoparticle-based competitive colorimetric assay can detect mismatched
      DNAs using MutS, a mismatch binding protein, and determine their relative binding
      affinities for this protein by a simple color change and the melting temperature
      of DNA-functionalized nanoparticle assemblies.

PMID- 18815688
TI  - An organopalladium chromogenic chemodosimeter for the selective naked-eye
      detection of Hg(2+) and MeHg(+) in water-ethanol 1 : 1 mixture.
AB  - An organopalladium chemical dosimeter of Hg(2+) that methylates Hg(2+),
      undergoing a colour change in 1 : 1 ethanol-water with submicromolar sensitivity,
      gives rise to an aqua-palladium complex that is methylated by MeHg(+) in the
      presence of a dithiol compound, undergoing another colour change, thus making the
      system suitable for the naked-eye detection of Hg(2+) and MeHg(+), two
      environmentally important species of Hg(2+).

PMID- 18815689
TI  - Apoferritin protein cages: a novel drug nanocarrier for photodynamic therapy.
AB  - A methylene blue-encapsulated apoferritin complex shows cytotoxic effects on MCF
      7 human breast adenocarcinoma cells when irradiated at the appropriate
      wavelength.

PMID- 18815690
TI  - Mesogenic dipyrrins-building blocks for the fabrication of fluorescent and metal
      containing materials.
AB  - A new class of mesogenic dipyrrins is reported and their use in the fabrication
      of fluorescent and metal-containing self assembling materials is demonstrated.

PMID- 18815691
TI  - Type-II CdS nanoparticle-ZnO nanowire heterostructure arrays fabricated by a
      solution process: enhanced photocatalytic activity.
AB  - We report a two-step, solution-based synthetic method to fabricate CdS
      nanoparticles-sensitized ZnO nanowire heterostructure arrays which showed
      enhanced photocatalytic activities in comparison with bare ZnO nanowire arrays.

PMID- 18815692
TI  - A simple route for fabricating poly(para-phenylene vinylene) (PPV) particles by
      using ionic liquids and a solvent evaporation process.
AB  - Particles of a poly(para-phenylenevinylene) (PPV) precursor were prepared from an
      aqueous solution of the polymer by simple evaporation of water from the solution,
      which also contained an ionic liquid as a poor solvent (self-organized
      precipitation (SORP) method); PPV precursor nanoparticles were successfully
      converted to PPV nanoparticles after annealing at 240 degrees C under reduced
      pressure, this simple process constituting a novel route to nanoparticles of
      functional polymeric materials.

PMID- 18815693
TI  - [60]Fullerene-based liquid crystals acting as acid-sensitive fluorescent probes.
AB  - Functionalization of [60]fullerene with liquid-crystalline dendrimers and a
      dibutylaniline-based phenylenevinylene moiety leads to supramolecular materials,
      the fluorescence of which responds to acid-base stimuli.

PMID- 18815694
TI  - Borenium cations derived from BODIPY dyes.
AB  - Fluoride abstraction from a BODIPY dye gives a well defined borenium ion which
      can be converted to a borenium hydride via treatment with DIBAL-H.

PMID- 18815695
TI  - A BODIPY boronium cation for the sensing of fluoride ions.
AB  - In the presence of iodide ions, the cationic p-dimethylaminopyridine adduct of
      1,3,5,7,8-pentamethylpyrromethene-boron fluoride [-DMAP](+) reacts with fluoride
      ions to afford the corresponding brightly fluorescent difluoride -F.

PMID- 18815696
TI  - Direct observation of time and temperature dependent transition from spherical
      micelles to vesicles.
AB  - An interesting transition from spherical micelles to vesicles, which was time and
      temperature dependent, was observed for the first time; it is tentatively
      attributed to the thermal hysteresis of temperature-responsive poly(N
      isopropylacrylamide).

PMID- 18815697
TI  - Nanostructured polymers with embedded self-assembled reactive gel networks.
AB  - Generating polymers in the presence of a self-assembling gelator with terminal
      double bonds yields polymeric materials with embedded reactive nano-skeletons
      subsequent washing gives nanoscale imprinted materials with fibrillar
      architectures.

PMID- 18815698
TI  - Spontaneous formation of a chiral supramolecular superhelix in the crystalline
      state using a single-stranded tetranuclear metallohelicate.
AB  - An unprecedented one-handed coiled-coil structure was formed in the crystal of a
      Zn(3)La tetranuclear metallohelicate, in which the handedness of both the helical
      component and the helical array was well controlled by the chiral auxiliary of
      the flexible acyclic ligand.

PMID- 18815699
TI  - A facile method of achieving low surface coverage of Au nanoparticles on an
      indium tin oxide electrode and its application to protein detection.
AB  - Low surface coverage of Au nanoparticles on an indium tin oxide electrode for
      sensitive electrochemical detection was achieved using electrostatic adsorption
      of AuCl(4)(-) followed by reduction.

PMID- 18815700
TI  - Sulfate anion-templated assembly of a [2]catenane.
AB  - The sulfate anion's templating role in catenane formation is demonstrated for the
      first time; a novel bis-pyridinium nicotinamide [2]catenane is prepared in a
      remarkable high yield and is shown to exhibit selectivity for sulfate, the
      templating anion.

PMID- 18815701
TI  - The role of heterogeneous nucleation in the self-assembly of oligothiophenes.
AB  - The cooperative self-assembly of oligothiophenes can be characterized by
      heterogeneous nucleation caused by trace amounts of impurities leading to a
      manifold of supramolecular arrangements.

PMID- 18815702
TI  - Grating of single Lu@C(82) molecules using supramolecular network.
AB  - A supramolecular grating of single Lu@C(82) molecules was obtained by depositing
      Lu@C(82) molecules onto a room temperature PTCDI-melamine network.

PMID- 18815703
TI  - Diversity-oriented synthesis of novel polycyclic scaffolds using polymer-bound
      reagents.
AB  - A concise sequence utilizing a Petasis three component reaction followed by a
      tandem aza-Cope-Mannich cyclization afforded novel polycyclic heterocycles in
      good yield; alternative iminium cyclization based on a Pictet-Spengler reaction
      or aminal formation led to divergent pathways affording skeletal diversity.

PMID- 18815704
TI  - Superparamagnetic iron oxide nanoparticles with photoswitchable fluorescence.
AB  - The incorporation of superparamagnetic iron oxide nanoparticles with sulfur
      oxidized diarylethene molecules resulted in a novel multifunctional nanosystem,
      in which the fluorescent performance and flocculation and dispersion are
      reversibly switched by light irradiation and external magnetic field,
      respectively.

PMID- 18815705
TI  - The fragmentation of gold nanoparticles induced by small biomolecules.
AB  - Spherical gold nanoparticles (3-5 nm) undergo a surprising fragmentation without
      extra energy input and are converted into ultrasmall particles (less than 1.5
      nm), which is a direct result of electron transfer between gold nanoparticles and
      cysteine.

PMID- 18815706
TI  - Total synthesis of a potent hybrid of the anticancer natural products
      dictyostatin and discodermolide.
AB  - A potent dictyostatin-discodermolide hybrid was designed and synthesised; it
      showed enhanced cell growth inhibitory activity relative to discodermolide in
      four human cancer cell lines including the Taxol-resistant NCI/ADR-Res cell line.

PMID- 18815707
TI  - Synergy between Bronsted acid sites and Lewis acid sites.
AB  - Synergy between Bronsted acid sites and Lewis acid sites in mesoporous Al-Zr-TUD
      1 was demonstrated to exist in Bronsted acid catalysed reactions, but not in
      Lewis acid catalysed reactions.

PMID- 18815708
TI  - Photocatalytic hydroxylation of aromatic ring by using water as an oxidant.
AB  - Electrophilic oxygen species photocatalytically derived from water molecules can
      selectively react with the aromatic ring of both benzene and its derivatives to
      produce the corresponding phenols and hydrogen over platinum-loaded titanium
      oxide when illuminated with light of appropriate wavelength in the absence of
      oxygen.

PMID- 18815709
TI  - Highly enantioselective organocatalytic formation of a quaternary carbon center
      via chiral Bronsted acid catalyzed self-coupling of enamides.
AB  - The enantioselective BINOL-phosphate catalyzed formation of a quaternary carbon
      center, bearing a N-atom has been achieved through the self-coupling reaction of
      enamides; the corresponding products have been isolated in up to >99% ee and
      their application for the synthesis of versatile synthetic building blocks-beta
      aminoketones-has been demonstrated.

PMID- 18815710
TI  - Synthesis of nanoscale carceplexes from deep-cavity cavitands.
AB  - Deep-cavity cavitands were shown to undergo carceplex reactions in which two
      cavitand tetrols were covalently linked using bromochloromethane; the efficiency
      of the "dimerization" was closely tied to the templating guest molecule
      incarcerated within the host.

PMID- 18815711
TI  - Ge(14)[Ge(SiMe(3))(3)](5)Li(3)(THF)(6): the largest metalloid cluster compound of
      germanium: on the way to fullerene-like compounds?
AB  - The reaction of GeBr with LiGe(SiMe(3))(3) yields the largest metalloid cluster
      compound of germanium Ge(14)[Ge(SiMe(3))(3)](5)Li(3)(THF)(6), in which 14
      germanium atoms are arranged as a hollow sphere in the cluster core, showing that
      in the case of germanium also fullerene-like compounds might be present in the
      borderland between the molecular and solid states.

PMID- 18815712
TI  - Partial sick leave--review of its use, effects and feasibility in the Nordic
      countries.
AB  - Partial sick leave and partial sickness benefits are currently available in
      Sweden, Norway, Denmark, and Finland. The literature was reviewed to determine
      their use, describe their recipients, find evidence of their effects, and explore
      attitudes towards and experiences with their use. Eight databases were searched.
      National sickness absence statistics and other relevant sources were also
      reviewed. Of the sickness benefits, partial benefits accounted for approximately
      one-fifth in Norway, less than 10% in Denmark, and over a third in Sweden. In
      Finland, partial sick leave was seldom used during the first year (2007) of
      benefit availability. Few peer-reviewed studies on its effects were identified,
      and scientific evidence was scarce. Its acceptance was good in all four
      countries. Most of the recipients were women and over 45 years of age. Studies of
      its feasibility seem congruent in reporting hindrances due to inflexible work
      arrangements and poor collaboration between actors. More research and more
      rigorous study designs are needed to determine whether partial sick leave is
      feasible and beneficial in keeping those with reduced work ability in worklife.

PMID- 18815713
TI  - Are occupational factors important determinants of socioeconomic inequalities in
      musculoskeletal pain?
AB  - OBJECTIVES: The aim of this study was to quantify socioeconomic inequalities in
      low-back pain, neck-shoulder pain, and arm pain in the general working population
      in Oslo and to examine the impact of job characteristics on these inequalities.
      METHODS: All economically active 30-, 40-, and 45-year-old persons who attended
      the Oslo health study in 2000-2001 and answered questions on physical job
      demands, job autonomy, and musculoskeletal pain were included (N=7293).
      Occupational class was used as an indicator of socioeconomic status. The lower
      occupational classes were compared with higher grade professionals, and
      prevalences, prevalence ratios, prevalence differences, and population
      attributable fractions were calculated. RESULTS: There were marked, stepwise
      socioeconomic gradients for musculoskeletal pain, steeper for the men than for
      the women. The relative differences (prevalence ratios) were larger for low-back
      pain and arm pain than for neck-shoulder pain. The absolute differences
      (prevalence differences) were the largest for low-back pain. Physical job demands
      explained a substantial proportion of the absolute occupational class
      inequalities in low-back pain, while job autonomy was more important in
      explaining the inequalities in neck-shoulder pain and arm pain. The estimated
      population attributable fractions supported the impact of job characteristics at
      the working population level, especially for low-back pain. CONCLUSIONS: In this
      cross-sectional study, physical job demands and job autonomy explained a
      substantial proportion of occupational class inequalities in self-reported
      musculoskeletal pain in the working population in Oslo. This finding indicates
      that the workplace may be an important arena for preventive efforts to reduce
      socioeconomic inequalities in musculoskeletal pain.

PMID- 18815714
TI  - Exposure to environmental tobacco smoke and health effects among hospitality
      workers in Sweden--before and after the implementation of a smoke-free law.
AB  - OBJECTIVES: This study attempted to identify changes in exposure to environmental
      tobacco smoke, as well as symptoms and attitudes among hospitality workers after
      the introduction of extended smoke-free workplace legislation. METHODS: A total
      of 37 volunteers working in bingo halls and casinos (gaming workers) and 54 bars
      and restaurant employees (other workers) in nine Swedish communities participated
      in the study. Altogether 71 of 91 persons (14 daily smokers and 57 nonsmokers)
      participated in both the pre-ban baseline survey and the follow-up 12 months
      after the ban. Exposure to environmental tobacco smoke, smoking habits,
      respiratory and sensory symptoms, and attitudes towards the ban were recorded,
      and spirometry was carried out. RESULTS: The frequency of reported respiratory
      and sensory symptoms was approximately halved among the nonsmokers in both
      occupational groups after the introduction of the ban. Initially 87% had exposure
      to environmental tobacco smoke that was over the nicotine cut-off level chosen to
      identify possible health risk ( <0.5 microg/m3) while, after the ban, it was only
      22%, a relative risk of 0.25 (95% confidence interval 0.15-0.41). The risk
      decreased in both occupational groups, but gaming workers experienced the highest
      pre-ban exposure levels. Attitudes towards the legislation were largely positive,
      particularly after the ban. However, there was no notable change in lung
      function, and there was no notable reduction in the number of cigarettes consumed
      by smokers. CONCLUSIONS: The introduction of smoke-free legislation was
      associated with a substantial reduction in respiratory and sensory symptoms, as
      well as reduced exposure to environmental tobacco smoke at work, particularly
      among gaming workers.

PMID- 18815715
TI  - Influence of job strain on changes in body mass index and waist circumference--6
      year longitudinal study.
AB  - OBJECTIVES: This study examined the effect of changes in psychosocial workplace
      characteristics on weight gain and abdominal obesity. METHODS: Twice, at an
      interval of 6 years, the authors conducted examinations of job demand-control
      support and measurements of body mass index and waist circumference among 2200
      men and 1371 women aged 30-53 years and working in a factory. The scores of the
      psychosocial work characteristics in each examination were dichotomized at the
      median values for the men and women separately and then categorized into three
      groups as follows: group I: low score in both the first and second examinations,
      group II: low score in the first examination and high score in the second (or
      high at the first and low at the second), and group III: high in both the first
      and second examinations. RESULTS: Although there was no statistically significant
      association between psychosocial work characteristics and the change in body mass
      index, for both genders, the change in waist circumference increased more in
      group III than in group I. Similarly, the odds ratios for the change in waist
      circumference above the 75th percentile for groups II and III increased more than
      in group I, being 1.13 [95% confidence interval (95% CI) 0.87-1.46 and 1.39 (95%
      CI 1.07-1.79) for the men in groups II and III, respectively, and 1.27 (95% CI
      0.90-1.78) and 1.78 (95% CI 1.26-2.52) for the women in groups II and III,
      respectively. CONCLUSIONS: The results suggest that high job strain is a risk
      factor for increased abdominal obesity.

PMID- 18815716
TI  - Blue-enriched white light in the workplace improves self-reported alertness,
      performance and sleep quality.
AB  - OBJECTIVES: Specifications and standards for lighting installations in
      occupational settings are based on the spectral sensitivity of the classical
      visual system and do not take into account the recently discovered melanopsin
      based, blue-light-sensitive photoreceptive system. The authors investigated the
      effects of exposure to blue-enriched white light during daytime workhours in an
      office setting. METHODS: The experiment was conducted on 104 white-collar workers
      on two office floors. After baseline assessments under existing lighting
      conditions, every participant was exposed to two new lighting conditions, each
      lasting 4 weeks. One consisted of blue-enriched white light (17 000 K) and the
      other of white light (4000 K). The order was balanced between the floors.
      Questionnaire and rating scales were used to assess alertness, mood, sleep
      quality, performance, mental effort, headache and eye strain, and mood throughout
      the 8-week intervention. RESULTS: Altogether 94 participants [mean age 36.4 (SD
      10.2) years] were included in the analysis. Compared with white light (4000 K),
      blue-enriched white light (17 000 K) improved the subjective measures of
      alertness (P<0.0001), positive mood (P=0.0001), performance (P<0.0001), evening
      fatigue (P=0.0001), irritability (P=0.004), concentration (P<0.0001), and eye
      discomfort (P=0.002). Daytime sleepiness was reduced (P=0.0001), and the quality
      of subjective nocturnal sleep (P=0.016) was improved under blue-enriched white
      light. When the participants' expectation about the effect of the light
      treatments was entered into the analysis as a covariate, significant effects
      persisted for performance, alertness, evening fatigue, irritability, difficulty
      focusing, concentrating, and blurred vision. CONCLUSIONS: Exposure to blue
      enriched white light during daytime workhours improves subjective alertness,
      performance, and evening fatigue.

PMID- 18815717
TI  - Impact of retirement on risky driving behavior and attitudes towards road safety
      among a large cohort of French drivers (the GAZEL cohort).
AB  - OBJECTIVES: This study investigated changes in driving behavior and attitudes
      towards road safety, following retirement, in a large cohort of road users.
      METHODS: In 2001, 14 226 participants of the GAZEL cohort in France reported
      their attitudes towards road safety and driving behavior using a self
      administered driving behavior and road safety questionnaire. In 2004, 82% of the
      group (N=11 706) responded to the same questionnaire. Two complementary logistic
      regression analyses were performed to assess the association of (i) retirement
      with change in safe driving behavior and attitudes towards road safety between
      2001 and 2004 and (ii) time since retirement with risky driving behavior and
      negative attitudes towards road safety in 2001. RESULTS: Among the participants
      who were active in 2001 (N=3927), those retiring between 2001 and 2004 (66%) were
      more likely to have discontinued sleepy driving [adjusted odds ratio (aOR) 2.12,
      P<0.001] and phone use while driving (aOR 1.74, P=0.006) than those who remained
      professionally active. The second analysis showed that the likelihood of sleepy
      driving and phone use while driving decreased soon after retirement, whereas that
      of speedy driving decreased over a longer interval. Retirement had no influence
      on driving while intoxicated or attitudes towards road safety. CONCLUSIONS: The
      results suggest that any professional activity may account for some risky road
      behavior. As work-related road traffic accidents are responsible for one out of
      every four road casualties in France, the monitoring and prevention of sleepy
      driving and phoning while driving among workers should be further considered.

PMID- 18815718
TI  - Meteorological conditions and the diagnosis of occupationally related contact
      sensitizations.
AB  - OBJECTIVES: An accurate diagnosis of (occupational) contact sensitization by
      patch testing is a prerequisite for efficient preventive management. However,
      previously observed seasonal fluctuations in patch-test reactions indicate some
      influence of meteorological conditions. The present analysis aims at quantifying
      the possible impact of temperature and humidity on patch-test reactions to
      occupationally related allergens. METHODS: Clinical data from 61 780 patients
      tested with standard series allergens potentially related to occupational
      exposure from 1993 through 2001 were collected by a contact sensitization
      surveillance network.The association between the patch-test results and
      meteorological data (air temperature and humidity) collected at the time and the
      approximate location of the testing was analyzed in a multinomial logistic
      regression analysis. RESULTS: For three allergens (a dye and two biocides), the
      odds of irritant or doubtful allergic reactions increased during cold and arid
      conditions. Two of them (pphenylenediamine and formaldehyde) also showed an
      association between weak positive allergic reactions and such weather. In
      contrast, reactions to various adhesive, plastic, and rubber-related allergens
      were not associated with weather conditions. CONCLUSIONS: An overall increase in
      skin irritation, brought on by cold and dry conditions, may instigate an increase
      in positive reactions by leading doubtful allergic reactions to be (falsely)
      categorized as allergic for at least two of the considered allergens. For the
      most part, however, weather conditions were not associated with reactions to
      occupational allergens. Thus the validity of patch testing does not largely seem
      to be compromised by ambient meteorological conditions.

PMID- 18815719
TI  - PCB contamination assessment of yusho patients by using preserved human umbilical
      cord.
AB  - PCB concentrations in umbilical cord preserved from the time when Yusho patients
      and healthy subjects gave birth were examined. The total concentration of the 12
      DL-PCB isomers ranged from 130 to 12,000 pg/g in the umbilical samples, was about
      700 pg/g around 1950 but began to increase in the mid 1960s, reached about 12,000
      pg/g between 1968 and 1970 immediately after the Yusho incident. However, the DL
      PCB concentration was high between 1968 and 1970 in not only the designated Yusho
      patients but also healthy subjects, and the maximum DL-PCB concentration was
      close between the two groups.

PMID- 18815720
TI  - Bladder erosion after 2 years from cystocele repair with type I polypropylene
      mesh.
AB  - Type I polypropylene mesh have been widely used in gynaecologic surgery for the
      treatment of pelvic organ prolapse and stress urinary incontinence. Such devices
      produced positive results compared to the equivalent non-mesh-based operation but
      erosions into adjacent viscera, especially the vagina, have also been reported.
      We describe the case of bladder erosion that manifested two years after the
      initial cystocele repair surgery and the management adopted.

PMID- 18815722
TI  - Body composition obtained from the body mass index: an Italian study.
AB  - BACKGROUND: Since obesity and related diseases are now considered epidemic, new
      and more accurate formulas for epidemiological studies are of interest to the
      scientific community. Several equations have been proposed to estimate the body
      composition simply from anthropometric measurements. However, with time, the body
      composition of the populations studied changes in relation to their food habits
      and lifestyle, and, therefore, the equations must be regularly updated and
      corrected. AIM OF THE STUDY: The aim of the study was to develop new equations to
      determine the body composition among the Italian population using the body mass
      index and independently by variables such as age and body structure. METHODS:
      Bioelectrical impedance and anthropometric analysis of 764 Italian Caucasian
      subjects (342 females and 422 males), 11 to 80 years of age, were analysed.
      Females and males were analysed separately. Multiple regression analyses were
      performed in order to estimate the body composition of the subjects. The
      estimated masses were then compared with the measured masses using Bland and
      Altman plots. We also calculated the differences between the estimated and
      measured masses, reported as % of the body weight, for the 95, 85 and 75 degrees
      percentile of the female and male groups. Finally we compared our formulas with
      the Watson equations, which are used to estimate the total body water. RESULTS:
      All body masses estimated were positively correlated to the measured values.
      Moreover, at any percentile analysed, our formulas resulted more precise than the
      Watson formula. Equations: Females: FM = 1.9337 BMI - 26.422; FFM = BW - FM; BCM
      = 0.3655 FFM + 4.865; TBW = 0.5863 FFM + 7.1732; Males: FM = 1.407 BMI - 21.389;
      FFM = BW - FM; BCM = 0.4485 FFM + 3.3534; TBW = 0.6997 + 1.4567. CONCLUSIONS:
      Although an inevitable inaccuracy must be expected in epidemiological studies,
      our equations are adequate to analyze the body composition state and changes
      occurring among the Italian population by simply considering weight and height.

PMID- 18815723
TI  - Ascorbic acid uptake affects ferritin, Dcytb and Nramp2 expression in Caco-2
      cells.
AB  - BACKGROUND: Ascorbic acid (vitamin C) enhances iron uptake in human intestinal
      cells. It is commonly believed that the enhancement is due to the capacity of
      ascorbic acid to reduce ferric iron to ferrous iron. Other suggestions have
      recently been made about the effects of ascorbic acid on the cellular metabolism
      of iron. These effects must be investigated for several reasons. One important
      issue is to study whether ascorbic acid has effects on iron metabolism in the
      absence of extracellular iron in the intestinal lumen. AIM OF THE STUDY: The aim
      of this investigation was to determine whether cellular uptake of ascorbic acid
      affects iron acquisition in the Caco-2 cell line. The possible event was
      investigated by studying the expression of the iron storage protein ferritin, the
      iron uptake protein Nramp2 and a duodenal ferric reductase Dcytb after incubating
      ascorbic acid deficient or ascorbic acid fed cells with iron and/or ascorbic
      acid. METHODS: The above stated interactions were studied in the human Caco-2
      cell model. Cell lysates were collected and subjected to SDS-PAGE and Western
      blotting. The blotted samples were stained with specific antibodies (Rabbit alpha
      human-Nramp2 and Goat alpha-human Dcytb) against the respective proteins and the
      bands achieved were analysed by reflective density measurements. The cellular
      ferritin content was analysed with a commercial kit and the intracellular
      ascorbic acid concentration was measured by HPLC. RESULTS: The results indicate
      that ascorbic acid uptake induces both iron independent and iron dependent
      ferritin formation, but the effect on iron dependent ferritin expression was
      significantly greater (470% compared to 19%). Western Blot analyses revealed a
      long term down-regulating effect of ascorbic acid on iron independent and iron
      dependent Nramp2 and Dcytb expression. However, the down-regulation of Dcytb was
      in general more extensive than that of Nramp2 (31-50% compared to 8-29%). In a
      second study of short term Nramp2 and Dcytb expression, the results suggested
      that both proteins were significantly up-regulated by ascorbic acid, regardless
      of intracellular ascorbic acid status. However, the impact of iron alone on
      Nramp2 up-regulation seems to be greater in the absence of ascorbic acid.
      CONCLUSIONS: The influence of intracellular ascorbic acid status on ferritin
      formation must be considered in iron uptake studies in Caco-2 cells. This could
      be a cause of diverging inter-laboratory results. The long term down-regulation
      of Nramp2 and Dcytb seems to correlate with results of human studies, where long
      term ascorbic acid supplementation does not affect iron status. Similarly, the
      short term up-regulation of Nramp2 and Dcytb seems to agree with the improvement
      in iron uptake shown in humans when single doses of ascorbic acid were
      administrated. These results are important for the understanding of the impact of
      ascorbic acid on iron status and will hopefully lead to further investigations on
      the matter.

PMID- 18815724
TI  - Complete nucleotide sequence analysis of a Dengue-1 virus isolated on Easter
      Island, Chile.
AB  - Dengue-1 viruses responsible for the dengue fever outbreak in Easter Island in
      2002 were isolated from acute-phase sera of dengue fever patients. In order to
      analyze the complete genome sequence, we designed primers to amplify contiguous
      segments across the entire sequence of the viral genome. RT-PCR products obtained
      were cloned, and complete nucleotide and deduced amino acid sequences were
      determined. This report constitutes the first complete genetic characterization
      of a DENV-1 isolate from Chile. Phylogenetic analysis shows that an Easter Island
      isolate is most closely related to Pacific DENV-1 genotype IV viruses.

PMID- 18815725
TI  - Methotrexate for the treatment of juvenile idiopathic arthritis: process to
      approval for JIA indication in Japan.
AB  - Methotrexate (MTX), the primary treatment for the articular-type juvenile
      idiopathic arthritis (JIA), is effective and brings about radiological
      improvement. Patient compliance is good, and it is recognized that its known side
      effects, namely, disruption of liver function and induction of pulmonary lesions,
      are unlikely to be severe at the low MTX doses that are administered. In Japan,
      MTX was granted approval in 1999 by the then Ministry of Health and Welfare
      specifically for treating rheumatoid arthritis in adult patients, allowing it be
      generally used in medical institutions for patients having National Health
      Insurance. However, in the pediatric field, its use outside the indications has
      so far been unavoidable, and has been left to the discretion of the physician.
      Finally, at the present conference, expansion of the indications of MTX for JIA
      was approved in Japan. It is noteworthy that this expansion of indications was
      achieved without requiring clinical trials on children sponsored by the
      pharmaceutical company: it was achieved rather by collecting necessary
      information through ongoing efforts (including collection and analysis of
      information about approval status in foreign countries, adequate evidence from
      the literature, implementation of a clinical use survey in Japan, etc.). It also
      merits attention that the maximum dose (10 mg/m2) was set on the basis of
      pharmacokinetic data from children, rather than relying on the dosing method and
      dose for adults.

PMID- 18815726
TI  - Multicentric Castleman's disease presenting with multiple nodes in lungs: a case
      report and literature review.
AB  - We report a rare multicentric Castleman's disease case whose lung manifestation
      is severe than any known report. This is a 64-year-old woman, she had repeated
      cough, fever and breathlessness for more than 1 year. CT imaging showed multiple
      small nodules in both the lungs at the first onset. Large nodes and masses in
      both the lungs evolved 1 year later. After three times of lung biopsies (one
      video-assisted thoracoscopic surgery and two CT-guided percutaneous
      transthoracic), she was finally diagnosed as multicentric Castleman's disease.
      She got surprising relief after combination chemotherapy in spite of her severe
      lung changes.

PMID- 18815727
TI  - Tolerability and efficacy of a combination of paracetamol and caffeine in the
      treatment of tension-type headache: a randomised, double-blind, double-dummy,
      cross-over study versus placebo and naproxen sodium.
AB  - The main aim of this study was to confirm in an Italian population affected by
      tension-type headache (TTH) the good profile of safety and tolerability of the
      combination paracetamol 1,000 mg-caffeine 130 mg (PCF) observed in previous
      studies, by a comparison with naproxen sodium 550 mg (NAP) and placebo (PLA). A
      secondary objective was to assess the efficacy of PCF in the acute treatment of
      TTH. This was a multicentre, randomised, double-blind, double-dummy, crossover,
      placebo-controlled trial. Tolerability was assessed by recording adverse events
      by the patient in the 4-h post-dose treatment. To assess the efficacy, the sum of
      pain intensity differences (SPID) and the total pain relief (TOTPAR) were
      calculated. Comparing PCF and NAP and PCF and PLA for tolerability, the
      difference was nonsignificant but the result regarding noninferiority was
      inconclusive, whilst NAP was noninferior to PLA. As regards SPID and TOTPAR, both
      PCF and NAP were better than placebo (P < 0.05), but not significantly different
      from each other. In conclusion, PCF was well-tolerated and effective in the
      treatment of acute TTH.

PMID- 18815728
TI  - A phase II study of S-1 plus irinotecan and oxaliplatin in heavily-treated
      patients with metastatic colorectal cancer.
AB  - Three-drug combination of fluoropyrimidine, irinotecan and oxaliplatin has shown
      survival benefits in patients with metastatic colorectal cancer (mCRC). Recently
      we performed a phase II study of a new 3-drug regimen, TIROX (S-1 plus irinotecan
      and oxaliplatin) to evaluate efficacy and safety in refractory mCRC patients.
      Patients with refractory to all of 3 drugs, age > or = 18 years, PS 0-2, > or = 1
      measurable lesion(s) and adequate organ functions were eligible. S-1 was given 40
      mg/m(2) twice a day on D1-14, oxaliplatin 85 mg/m(2) and irinotecan 150 mg/m(2)
      on D1 every 3 weeks. The primary endpoint was overall response rate (ORR).
      Between Mar 2007 and Nov 2007, 19 patients (of 18 planned) were enrolled; median
      age 50 years; M/F 12/7; PS 0/1/2 5/13/1; colon/rectum 11/8. By intent-to-treat
      analysis, ORR was 21.1% (95% CI, 8.7-43.7) and disease control rate was 52.6%
      (95% CI 31.5-72.8) with four PRs and six SDs. Median duration of disease control
      was 4.3 months (95% CI 1.7-6.9). Median PFS was 2.6 months (95% CI 2.2-2.9) and
      median OS was 9.8 months (95% CI 5.3-14.4) after median F/U of 15.4 months. G3/4
      toxicities per pt included neutropenia (five, 26.3%), febrile neutropenia (two,
      10.5%), thrombocytopenia (one, 5.3%), diarrhea (two, 10.5%) and fatigue (two,
      10.5%). TIROX seemed to be feasible and efficacious for refractory mCRC patients,
      and could be an alternative for patients with good PS but no further treatment
      options.

PMID- 18815729
TI  - Rhodamine-loaded poly(lactic-co-glycolic acid) nanoparticles for investigation of
      in vitro interactions with breast cancer cells.
AB  - Nanoparticle-based drug delivery systems are considered promising for the
      delivery of imaging agents and drugs for the detection and treatment of
      illnesses, including cancer. Investigation of nanoparticle interactions with the
      diseased cells can lead to better designs. In this work, poly(lactic-co-glycolic
      acid) nanoparticles loaded with rhodamine 6G were prepared by nanoprecipitation
      with high encapsulation efficiency. In vitro release studies demonstrated that
      rhodamine escaped from the nanoparticles at a very slow rate at physiological pH,
      thus making it ideal for imaging studies. At acidic pH this agent was released
      quickly, suggesting charge interactions between the polymer and rhodamine.
      Microscopy and flow cytometry studies show higher uptake in MDA-MB-231 breast
      cancer cells when exposed to rhodamine-loaded nanoparticles than to rhodamine in
      solution.

PMID- 18815730
TI  - Enhancing growth and proliferation of human gingival fibroblasts on chitosan
      grafted poly (epsilon-caprolactone) films is influenced by nano-roughness
      chitosan surfaces.
AB  - The bioactivity of poly (epsilon-caprolactone) (PCL) films is improved by
      grafting chitosan (CS) surfaces with various values of nano-roughness on PCL
      surfaces. To examine the effects of the design, growing human gingival
      fibroblasts (HGFs) on the films was conducted. Various values of nano-rough CS
      surfaces were cast using nano-rough PCL molds that had been fabricated using a
      solvent-etched technique. The features of nano-CS/PCL surfaces were characterized
      using an atomic force microscope (AFM) to observe the topography and to determine
      the value of centerline average roughness of a surface, R(a). The R(a) values of
      the nano-CS/PCL films were 36.8 +/- 1.6, 100.0 +/- 3.0, and 148 +/- 7.0 nm, while
      that of the smooth CS/PCL film was 12.5 +/- 1.6 nm. The growth and proliferation
      of HGFs on the films are elucidated by fluorescent staining and analyzed by MTT
      viability assay following three and 7 days of culture. The viability assay of the
      cells reveals that the growth rates of HGFs on both CS/PCL and nano-CS/PCL films
      significantly exceed (95% or more; P < 0.001) those of PCL on both days,
      demonstrating the improvement of the bioactivity of PCL films by grafting CS.
      Additionally, the growth rates and proliferations of HGFs on nano-CS/PCL films of
      roughness 100 and 148 nm markedly exceed (15% or more; P < 0.001) those on 36.8
      nm nano-CS/PCL and CS/PCL films, after both periods of culturing, indicating that
      the high nano-roughness CS surfaces further enhance the growth rate of HGFs. In
      conclusion, markedly improving the bioactivity of PCL films by grafting CS is
      demonstrated. Moreover, high nano-roughness of nano-CS/PCL films can further
      accelerate the growth and proliferation of HGFs compared with those of CS/PCL
      films. This work presents a new concept for designing biomaterials in tissue
      engineering.

PMID- 18815731
TI  - Degradable and bioresorbable polymers in surgery and in pharmacology: beliefs and
      facts.
AB  - The number of articles dealing with degradable polymers and macromolecules is
      increasing rapidly and the number of proposed compounds as well. However, not all
      have a high potential for effective applications. This contribution examines
      first the criteria to be taken into account when commercialisation of polymeric
      compounds and devices aimed at helping the body for a limited period of time,
      i.e. the healing time, is the main goal. What is really known is tentatively
      analysed by considering some of the candidates present in literature confronted
      to the targeted potential applications. Tentative comments are made on what
      should be done to qualify a candidate. Last but not least, trends in the search
      for polymers to be exploited in presently attracting areas such as bioresorbable
      stents, hydrogels to deliver bioactive macromolecules like proteins and
      polynucleotides or polyelectrolytes to temporarily complex charged
      biomacromolecules like proteins or genes are considered.

PMID- 18815732
TI  - Effect of ultrasound on the setting characteristics of glass ionomer cements
      studied by Fourier transform infrared spectroscopy.
AB  - OBJECTIVE: To investigate the effect of ultrasound (US) application, US staring
      time and US duration on the setting of glass ionomer cement (GIC) by using
      Attenuated Total Reflectance Fourier Transform Infrared (ATR/FTIR) spectrometer.
      METHODS: Two conventional GICs, Fuji IX Fast and Ketac Molar were studied. US
      application was started at 30 s or 40 s after mixing and was applied for times
      between 15 and 55 s on samples of two different thicknesses. The samples were
      analysed using ATR/FTIR. RESULTS: US accelerated the curing process in both
      cements, US needed to be applied for more than 15 s. Both Fuji IX and Ketac Molar
      showed increased setting on increasing the US application duration from 15 s to
      55 s. Increased setting of the GICs was produced when US application started 40 s
      after mixing rather than 30 s after mixing. CONCLUSIONS: The significant findings
      of the study include that US application accelerated the setting processes, by
      accelerating the formation of the acid salts. The salt formation increased with
      increase time of US application. The effect of application of US to setting GICs
      is influenced by time of the start of application of the US. The effects appear
      to material specific, with Ketac Molar showing a greater effect than Fuji IX.

PMID- 18815733
TI  - Transfer of a minimal linear marker-free and vector-free smGFP cassette into
      soybean via ovary-drip transformation.
AB  - A tissue culture-independent plant transformation method, called ovary-drip
      transformation, was established in which a minimal linear gene cassette [35S CaMV
      promoter, open reading frame of soluble modified green fluorescent protein
      (smGFP), and NOS terminator] was transformed into soybean. The method is
      characterized by directly dripping a DNA solution, which is supplemented with a
      surfactant, onto the ovary wound 6-8 h after self-pollination. The growth of the
      pollen tube was measured after self-pollination. The movement of smGFP across the
      passageway toward the embryo sac was monitored using fluorescein isothiocyanate
      labeled DNA. The transformation frequency reached 3.2% by PCR analysis. Southern
      analysis of the primary transformants denoted the integration of a single site
      smGFP. The transgenic plants exhibited a high level of smGFP expression which was
      visible in the immature embryos of the transgenic soybean.

PMID- 18815734
TI  - Effect of dimerization of a beta-turn antimicrobial peptide, PST13-RK, on
      antimicrobial activity and mammalian cell toxicity.
AB  - PST13-RK (KKKFPWWWPFKKK-NH(2)) is an improved derivative of tritrpticin adopting
      a beta-turn structure. In order to investigate the effect of dimerization of
      PST13-RK on antimicrobial activity and mammalian cell toxicity, we designed and
      synthesized its Cys- and Lys-linked dimers. The dimerization of PST13-RK resulted
      in a 2-4 fold decreased antimicrobial activity against Gram-positive and Gram
      negative bacteria. However, the dimers showed a large increase in mammalian cell
      toxicity against mouse NIH-3T3, human MDA-MB-361, and human A549 cells. These
      results suggested that PST13-RK is active as a monomer to bacterial cells but as
      an oligomer to mammalian cells. Since the dimeric PST13-RK is much more effective
      against the cancer cells than the monomer, it might be an attractive candidate
      for anticancer chemotherapeutic drugs.

PMID- 18815736
TI  - Bioavailability of olive oil phenolic compounds in humans.
AB  - Olive oil is a functional food, which in addition to having a high level of
      monounsaturated fatty acids (MUFA), also contains multiple minor components,
      among them several phenolic compounds. Oleuropeine and its glycoside are the main
      sources of a simple phenol hydroxytyrosol with a strong antioxidant activity.
      Hydroxytyrosol is well absorbed in the gastrointestinal tract but its
      bioavailability is poor because an important first past metabolism both in gut
      and liver, leading to the formation of sulphate and glucuronide conjugates, to
      the extent that concentrations in body fluids of its free form are almost
      undetectable. This is a major drawback in our understanding of the antioxidant
      activity of this compound in vivo and the potential health benefits derived from
      its consumption. The picture is further compounded by the fact that
      hydroxytyrosol is also a dopamine metabolite and body fluids concentrations
      combine exogenous and endogenous sources.

PMID- 18815735
TI  - The challenge of developing green tea polyphenols as therapeutic agents.
AB  - The health benefits of green tea and its main constituent (-)-epigallocatechin
      gallate [(-)-EGCG] have been widely supported by results from epidemiological,
      cell culture, animal and clinical studies. On the other hand, there are a number
      of issues, such as stability, bioavailability and metabolic transformations under
      physiological conditions, facing the development of green tea polyphenols into
      therapeutic agents. We previously reported that the synthetic peracetate of (-)
      EGCG has improved stability and better bioavailability than (-)-EGCG itself and
      can act as pro-drug under both in vitro and in vivo conditions. Analogs of
      catechins have been synthesized and their structure activity relationship
      provides an understanding to the mechanism of proteasome inhibition. Metabolic
      methylation of catechins leading to methylated (-)-EGCG may alter the biological
      activities of these compounds.

PMID- 18815737
TI  - Health benefits of isoflavones in functional foods? Proteomic and metabonomic
      advances.
AB  - There is currently considerable interest in the potential health benefits of
      isoflavones in functional foods and in the future prospects for the development
      of new products of benefit to the consumer. The potential health benefits of
      isoflavones may include protection against age-related diseases including
      cardiovascular disease, osteoporosis, hormone-dependent cancer and loss of
      cognitive function. The mechanisms involved may include weak oestrogenic action
      and antioxidant activity. Our proteomic investigations of changes in the human
      serum profile in response to the consumption of isoflavones in soya functional
      foods suggest potentially beneficial modulation of the levels of a number of
      serum proteins, including increased apolipoprotein E (involved in lipid
      metabolism) and caeruloplasmin (antioxidant and copper regulatory properties)
      levels and decreased alpha-1-acid glycoprotein (involved in immunomodulation)
      levels that may contribute to vascular protection. Furthermore, preliminary
      metabonomic data indicates an alteration in the urinary metabolite profile after
      isoflavone consumption, which may be of significance.

PMID- 18815738
TI  - Tea polyphenols benefit vascular function.
AB  - Tea, the most popular beverage worldwide, is consumed in three basic forms; green
      tea, black tea and oolong tea. Tea contains over 4,000 chemicals some of which
      are bioactive. In recent years there has been a mounting interest in
      understanding the cardiovascular and metabolic benefits of polyphenolic
      flavonoids in tea, which can be used as a supplement among patients. Diverse
      cardioprotective effects of consuming tea or tea polyphenols have been described
      on pathological conditions, e. g. hypertension, atherosclerosis, diabetics,
      hypercholesterolemia, obesity, and are attributed to antioxidative, anti
      thrombogenic, anti-inflammatory, hypotensive and hypocholesterolemic properties
      of tea polyphenols. This review focuses on cardiovascular benefits of tea
      polyphenols based on in vitro and in vivo studies on experimental animal models
      and on studies of human subjects in four areas: (1) vasorelaxant effect; (2)
      protective effect against endothelial dysfunction; (3) antioxidant effect and (4)
      hypolipidemic effect. We will briefly discuss the effects of tea on
      atherosclerosis and hypertension.

PMID- 18815739
TI  - Soy consumption for reduction of menopausal symptoms.
AB  - AIMS: To review current research on the effects of soy consumption on menopausal
      symptoms. METHODS: To review results of recent meta-analyses and individual
      clinical trials. MAIN RESULTS: One recent meta-analysis reported that isoflavone
      supplementation was associated with a 34% reduction in hot flashes, with
      increased efficacy as the baseline number of flashes and isoflavone dose
      increased. A second review concluded that consumption of at least 15 mg
      genistein, rather than total isoflavones, is responsible for the reduction in
      symptoms. Results of these two reviews are supported by most subsequent
      randomized controlled trials. CONCLUSIONS: Consumption of 30 mg/day of soy
      isoflavones (or at least 15 mg genistein) reduces hot flashes by up to 50 %. This
      total reduction includes that provided by "the placebo effect". The greatest
      benefit may be realized when the isoflavone-rich food or supplement is taken in
      divided doses by subjects who experience at least four hot flashes/day.

PMID- 18815740
TI  - Phytoestrogens and breast cancer: a complex story.
AB  - Genistein is an isoflavone with oestrogenic activity that is present in a variety
      of soy products as a constituent of complex mixtures of bioactive compounds,
      whose matrix profiles play an important role in determining the overall
      oestrogenic bioactivity of genistein. We review data on how the profile of soy
      bioactive compounds can modulate genistein-stimulated oestrogen-dependent tumour
      growth. Our research has focused on the effects of dietary genistein on the
      growth of oestrogen (E)-dependent mammary tumours both in vitro and in vivo.
      Genistein enhances the proliferation of E-dependent human breast cancer tumour
      growth. In a similar manner, dietary genistein stimulates tumour growth in the
      chemically-induced (NMU) mammary cancer rodent model. Genistin, the glycoside of
      genistein, simulates growth similar to that of genistein and withdrawal of either
      genistein or genistin results in tumour regression. The extent of soy processing
      modulates the effects of dietary genistein in vivo as soy protein isolate, a
      highly purified and widely used source of protein that is processed to contain
      low, medium, and high amounts of isoflavones, stimulate the growth of the E
      dependent mammary tumours in a dose dependent manner. In contrast to the more
      purified diets, studies with soy flour of equivalent genistein levels did not
      stimulate the growth of E-dependent breast cancer tumours in vivo. However, the
      size of these tumours also did not regress as is observed in control groups in
      which oestrogen and genistein have been withdrawn. The expression of the
      oestrogen-target genes of pS2, progesterone receptor, and cyclin D1 correlates
      with the growth of E-dependent tumours and has been consistently observed to be
      induced in response to treatment with dietary genistein. To evaluate whether
      dietary genistein interacts with current anti-oestrogen breast cancer therapies
      such as tamoxifen (TAM), we implanted E-dependent tumours into ovariectomized
      athymic mice and administered oestradiol, oestradiol plus TAM, or oestradiol,
      TAM, and dietary genistein. In these studies dietary genistein was able to negate
      the inhibitory effect of TAM on E-stimulated tumour growth. In summary, genistein
      can act as an oestrogen agonist resulting in proliferation of E-dependent human
      breast cancer tumours in vivo and its activity can be modulated by the presence
      of other bioactive components in complex soy foods. Additionally, dietary
      genistein can negate the inhibitory effects of TAM on E-stimulated growth of MCF
      7 cell tumours implanted into ovariectomized athymic mice.

PMID- 18815741
TI  - Bioactive effects of olive oil phenolic compounds in humans: reduction of heart
      disease factors and oxidative damage.
AB  - Oxidative stress is defined as an imbalance between the oxidant and antioxidant
      systems of the body, in favour of the oxidants. Oxidative stress produced by free
      radicals has been linked to the development of several diseases such as
      cardiovascular, cancer, and neurodegenerative diseases. Olive oil is the main
      source of fat of the Mediterranean diet which has been shown to be effective
      against oxidative stress associated diseases and also with the ageing. Besides
      its richness in monounsaturated fatty acid, the oleic acid, olive oil contains
      minor components with antioxidant properties. Here, we update the state of the
      art, and degree of evidence, of the body of knowledge concerning the protective
      role on lipids and lipid oxidative damage in humans of the olive oil phenolic
      compounds.

PMID- 18815742
TI  - Soy isoflavones and their bone protective effects.
AB  - Several observational studies have suggested that populations with a high dietary
      soy intake have a lower incidence of osteoporosis-related fractures when compared
      to Western populations. However, there has not been consistent data to show that
      soy isoflavones protect against or lessen bone loss. Studies in our laboratory
      showed that genistein, the major soy isoflavone, could stimulate osteoblastic
      functions as well as human breast cancer cell growth. These studies raised the
      concern of whether it would be safe for women who have a prior history of breast
      cancer to consume soy isoflavone for management of postmenopausal osteoporosis.
      As increasing the purity of genistein is known to increase its ability to induce
      human breast cancer cell growth, current effort in our laboratory is to determine
      if the in vivo bone protective effects will be affected by the complexity of the
      soy isoflavones extract in ovariectomized mice.

PMID- 18815743
TI  - Green tea polyphenols as a natural tumour cell proteasome inhibitor.
AB  - The cancer-preventive effects of green tea and its main constituent (-)
      epigallocatechin gallate [(-)-EGCG] are widely supported by results from
      epidemiological, cell culture, animal and clinical studies although the molecular
      target has not been well defined. We previously reported that ester bond
      containing tea polyphenols, e. g. (-)-EGCG, and their synthetic analogs potently
      and specifically inhibited the proteasomal activity. Subsequently, we further
      demonstrated that methylation on green tea polyphenols under physiological
      conditions decreased their proteasome-inhibitory activity, contributing to
      decreased cancer-preventive effects of tea consumption. Since (-)-EGCG is
      unstable under physiological conditions, we also developed the peracetate
      protected or prodrug form of (-)-EGCG, Pro-EGCG (1), and shown that Pro-EGCG (1)
      increases the bioavailability, stability, and proteasome-inhibitory and
      anticancer activities of (-)-EGCG in human breast cancer cells and xenografts,
      suggesting its potential use for cancer prevention and treatment.

PMID- 18815744
TI  - Antioxidative activities and the total phenolic contents of tonic Chinese
      medicinal herbs.
AB  - Chinese medicated diet is an everyday practice in China. In this study, 16
      commonly used soup making tonic Chinese medicinal herbs were selected for
      antioxidative capacities by 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical
      scavenging activity and ferric reducing antioxidant power (FRAP), and the total
      phenolic contents of these herbal extracts were measured by the Folin-Ciocalteu
      method. It confirmed that drinking tonic soups could supplement total
      antioxidants intake. Amongst the tested herbal extracts, extracts of Canarium
      album Raeusch., Flos caryophylli and Fructus amomi were found to have the highest
      antioxidative activities in both DPPH and FRAP assays. Their antioxidative
      activities were comparable to ascorbic acid and butylated hydroxytoluene. Thus,
      these herbs are safe and inexpensive sources of natural antioxidants. A
      significant relationship between the antioxidative effects and total phenolic
      contents were found, indicating phenolic compounds are the major contributor of
      antioxidative capacities of these herbs. In addition, a strong correlation
      between DPPH assay and FRAP assay implied that antioxidants in these herbs were
      capable of scavenging free radicals and reducing oxidants.

PMID- 18815745
TI  - X-linked lymphoproliferative disease (XLP): a model of impaired anti-viral, anti
      tumor and humoral immune responses.
AB  - A major focus of our research is to understand the molecular and cellular basis
      of X-linked lymphoproliferative disease (XLP), a rare and often fatal
      immunodeficiency caused by mutations in the SH2D1A gene, which encodes the
      adaptor molecule SAP. Recently, we observed that SAP is essential for the
      development of natural killer T (NKT) cells, a lymphocyte population that
      participates in protection against certain tumors, infections, and autoimmune
      states. In this review, we describe the approaches that we are taking to
      understand the role of SAP in immune cells, including NKT cells. By using SAP as
      the focal point of our studies, we hope to identify novel signaling pathways that
      could be targeted to improve the treatment for patients with XLP as well as more
      common disorders, such as autoimmunity and cancer.

PMID- 18815746
TI  - Novel alpha-KTx sites in the BK channel and comparative sequence analysis reveal
      distinguishing features of the BK and KV channel outer pore.
AB  - The alpha-KTx peptide toxins inhibit different types of potassium channels by
      occluding the outer channel pore composed of four identical alpha subunits. The
      large-conductance, calcium-activated (BK or Slo1) and voltage-dependent (KV)
      potassium channels differ in their specificity for the different alpha-KTx
      subfamilies. While many different alpha-KTx subfamilies of different sizes
      inhibit KV1 channels with high affinity, only one subfamily, alpha-KTx 1.x,
      inhibits BK channels with high affinity. Two solvent-exposed regions of the outer
      pore that influence alpha-KTx binding, the turret and loop, display high sequence
      variability among different potassium channels and may contribute to differences
      in alpha-KTx specificity. While these alpha-KTx domains have been studied in KV1
      channels, little is known about the corresponding BK alpha-KTx domains. To define
      alpha-KTx sites in the BK outer pore, we examined the effect of 19 outer pore
      mutations on specific binding of 125I-labeled iberiotoxion (IbTX or alpha-KTx
      1.3) and on their cell-surface expression. Similar to alpha-KTx sites in the
      Shaker KV1 loop, site-directed mutations in the BK loop disrupted specific IbTX
      binding. In contrast, mutations in the BK turret region revealed three novel
      alpha-KTx sites, Q267, N268, and L272, which are distinct from alpha-KTx sites in
      the KV1 turret. The BK turret region shows no sequence identity with KV1 and MthK
      turrets of known 3D structure. To define the BK turret, we used secondary
      structure prediction methods that incorporated information from sequence
      alignment of 30 different Slo1 and Slo3 turret sequences from 5 of the 7 major
      animal phyla representing 27 different species. Results of this analysis suggest
      that the BK turret contains 18 amino acids and is defined by a cluster of
      strictly conserved polar residues at the N-terminal side of the turret. Thus, the
      BK turret is predicted to have six more amino acids than the KV1 turret. Results
      of this work suggest that BK and KV1 outer pores have a similar alpha-KTx domain
      in the loop preceding the inner helix, but that the BK turret comprises a unique
      alpha-KTx interaction surface that likely contributes to the exclusive
      selectivity of BK channels for alpha-KTx1.x toxins.

PMID- 18815749
TI  - Effects of the activities of key enzymes involved in starch biosynthesis on the
      fine structure of amylopectin in developing rice (Oryza sativa L.) endosperms.
AB  - The dynamic changes of the activities of enzymes involving in starch
      biosynthesis, including ADP-glucose pyrophosphorylase (AGPase), soluble starch
      synthases (SSS), starch branching enzyme (SBE) and starch debranching enzymes
      (DBE) were studied, and changes of fine structure of amylopectin were
      characterized by isoamylase treatment during rice grain development, using trans
      anti-waxy gene rice plants. The relationships between the activities of those key
      enzymes were also analyzed. The amylose synthesis was significantly inhibited in
      transgenic Wanjing 9522, but the total starch content and final grain weight were
      less affected as compared with those of non-transgenic Wanjing 9522 rice
      cultivar. Analyses on the changes of activities of enzymes involving in starch
      biosynthesis showed that different enzyme activities were expressed differently
      during rice endosperm development. Soluble starch synthase is relatively highly
      expressed in earlier stage of endosperm development, whilst maximal expression of
      granule-bound starch synthase (GBSS) occurred in mid-stage of endosperm
      development. No obvious differences in changes of the activities of AGPase and
      SBE between two rice cultivars investigated, except the DBEs. Distribution
      patterns of branches of amylopectin changed continually during the development of
      rice grains and varied between two rice cultivars. It was suggested that
      amylopectin synthesis be prior to the synthesis of amylose and different enzymes
      have different roles in controlling syntheses of branches of amylopectin.

PMID- 18815750
TI  - Immunological dynamics in response to two anthrax vaccines in mice.
AB  - In order to understand the variation of humoral and cellular immune responses to
      A16R live spore and AVA vaccine and to identify efficient immunological
      parameters for the early evaluation of post immunization in mice, we dynamically
      monitored the antibody production and cellular responses after the vaccination of
      Balb/C mice with the anthrax vaccines. The results show that both anti-AVA and
      anti-Spore antibodies were detectable in the A16R live spore vaccinated group
      while high titers of anti-AVA antibodies but not anti-Spore antibodies existed in
      the AVA-immunized group. IgG1 and IgG2 were the major subtypes of IgG in both of
      the two groups. However, the IgG2a level was significantly higher in the A16R
      group than in the AVA group. At the cellular level, responses of antigen-specific
      TH2, TH1 and plasma cells were detected. The peripheral T(H)2 responses could be
      seen on day 5 after vaccination, and remained at a high level throughout the
      experiment (from day 5 post primary immunization to day 60 post the tertiary
      immunization); the T(H)1 responses to A16R vaccine appeared on day 5, while the
      responses to AVA could only be detected by day 7 after the secondary
      immunization; a low level of T(H)1 responses could be observed at the end of the
      experiment. Antigen-specific plasma cells could be found in the peripheral blood
      of both the immunized groups, however, the responses in the A16R group appeared
      earlier, lasted longer, and shown an ascending tendency until the end of the
      experiment when the plasma cell responses in the AVA group were reduced to a very
      low level. The results suggest that the multiple antigen containing A16R live
      spore vaccine induces better immune responses than AVA. Combined with serum
      antibody titers, T(H)2, T(H)1 and plasma cell responses could be used as
      immunological parameters for the evaluation of vaccine efficacy. These findings
      may afford new insight into the early evaluation of vaccination as well as being
      a powerful strategy for vaccine development.

PMID- 18815751
TI  - Gene analysis of an antiviral protein SP-2 from Chinese wild silkworm, Bombyx
      mandarina Moore and its bioactivity assay.
AB  - The cDNA encoding an antiviral protein SP-2 against BmNPV was cloned from the
      midgut of Chinese wild silkworm, Bombyx mandarina Moore (GenBank access AY945210)
      based on the available information of the domesticated silkworm. Its cDNA was 855
      bp encoding 284 amino acids with predicted molecular weight of 29.6 kDa. Its full
      length in genomics was 1376 bp, including 5 exons and 4 introns. The expression
      analysis indicated that it was only expressed in midgut, and its expression level
      was higher during feeding stage of larval instars while very lower during the
      moltism and mature stages. The deduced amino acid sequence of this protein showed
      eight-amino-acid variation compared with the counterpart of domesticated
      silkworm. Its antiviral activity was assayed through in vitro test. The results
      indicated that it showed strong bioactivity against BmNPV, and its activity was
      1.6 fold higher that the counterpart of domesticated silkworm.

PMID- 18815752
TI  - Phototoxic effect of UVR on wild type, ebony and yellow mutants of Drosophila
      melanogaster: life span, fertility, courtship and biochemical aspects.
AB  - Melanin plays an important role in protecting organisms from ultraviolet
      radiation (UVR). Therefore, it is possible that differently colored strains can
      show different sensitivities to UVR. In the present work, life span, fertility
      and courtship behavior of wild type (w), ebony (e) and yellow (y) strains of
      Drosophila melanogaster were studied to evaluate their sensitivity to ultraviolet
      (UV). Because a range of phototoxic effects of UVR are mediated through
      generation of free radicals, levels of free radicals, lipid peroxide
      (malondialdehyde, MDA) and superoxide dismutase (SOD) activity of three strains
      were examined to indicate their antioxidant defending ability and oxidative
      status. It was shown that w always had the highest lifespan and fertility not
      only in the control but also in UV-exposed groups. Moreover, lifespan and
      fertility of e were significantly higher (P<0.0001) than those of y in the UV
      exposed groups, but not for the control. On the other hand, UV exposure had an
      adverse effect on courtship of flies. Stronger electron paramagnetic resonance
      (EPR) signals could be detected in w, e and y exposed to 5 min UV. And there were
      more significant changes of EPR signals in y than in w and e. UVR had no
      significant (P=0.1782) effect on the SOD activities. After pooling data from the
      control and UV-exposed groups, we found that w had a significantly (P<0.05)
      higher level of SOD activity, but e and y were nearly at the same levels
      (P>0.05). MDA levels were increased in the UV dose-dependent manner (P=0.0495).
      In conclusion, our results suggested that UVR can decrease life span and
      fertility of flies and do harm to courtship, which may be due to oxidative damage
      to flies tissues (e.g. central nervous system) induced by free radicals. w had
      the highest tolerance to UVR, which may be ascribed to its advantage of survival
      under the natural condition and at high level of SOD activity. Then differences
      of pigment between e and y in absorbing UV, shielding against UV and scavenging
      free radicals produced by UVR should be responsible for their different
      sensitivity to UVR.

PMID- 18815753
TI  - Coupling between elytra of some beetles: mechanism, forces and effect of surface
      texture.
AB  - Lightweight materials, structures and coupling mechanisms are very important for
      realizing advanced flight vehicles. Here, we obtained the geometric structures
      and morphologies of the elytra of beetles and ascertained its coupling zone by
      using the histological section technique and SEM. We set up a three-dimensional
      motion observing system to monitor the opening and closing behaviour of elytra in
      beetles and to determine the motion mechanism. We constructed a force measuring
      system to measure the coupling forces between elytra. The results show that
      elytra open and close by rotating about a single axle, where the coupling forces
      may be as high as 160 times its own bodyweight, the elytra coupling with the
      tenon and mortise mechanism, surface texture and opening angle between elytra
      heavily influence the coupling forces. These results may provide insights into
      the design mechanism and structure for future vehicles of flight.

PMID- 18815754
TI  - The universal fuzzy logical framework of neural circuits and its application in
      modeling primary visual cortex.
AB  - Analytical study of large-scale nonlinear neural circuits is a difficult task.
      Here we analyze the function of neural systems by probing the fuzzy logical
      framework of the neural cells' dynamical equations. Although there is a close
      relation between the theories of fuzzy logical systems and neural systems and
      many papers investigate this subject, most investigations focus on finding new
      functions of neural systems by hybridizing fuzzy logical and neural system. In
      this paper, the fuzzy logical framework of neural cells is used to understand the
      nonlinear dynamic attributes of a common neural system by abstracting the fuzzy
      logical framework of a neural cell. Our analysis enables the educated design of
      network models for classes of computation. As an example, a recurrent network
      model of the primary visual cortex has been built and tested using this approach.

PMID- 18815755
TI  - Simulation of blood flow in a small-diameter vascular graft model with a swirl
      (spiral) flow guider.
AB  - Small-diameter vascular grafts are in large demand for coronary and peripheral
      bypass procedures, but present products still fail in long-term clinical
      application. In the present communication, a new type of small-diameter graft
      with a swirl flow guider was proposed to improve graft patency rate. Flow pattern
      in the graft was simulated numerically and compared with that in a conventional
      graft. The numerical results revealed that the swirl flow guider could indeed
      make the blood flow rotate in the new graft. The swirling flow distal to the flow
      guider significantly altered the flow pattern in the new graft and the velocity
      profiles were re-distributed. Due to the swirling flow, the blood velocity near
      the vessel wall and wall shear rate were greatly enhanced. We believe that the
      increased blood velocity near the wall and the wall shear rate can impede the
      occurrence of acute thrombus formation and intimal hyperplasia, hence can improve
      the graft patency rate for long-term clinical use.

PMID- 18815756
TI  - Tracheal compliance and limit flow rate changes in a murine model of asthma.
AB  - Trachea is the unique passage for air to flow in and out. Its tone is of
      importance for the respiration system. However, investigation on how tracheal
      tone changes due to asthma is limited. Aiming at studying how the mechanical
      property changes due to asthma as well as the compliance and flow limitation, the
      following methods are adopted. Static and passive pressure-volume tests of rats'
      trachea of the asthmatic and control groups are carried out and a new type of
      tube law is formulated to fit the experimental data, based on which changes of
      compliance and limit flow rate are investigated. In order to give explanation to
      such changes, histological examinations with tracheal soft tissues are made. The
      results show that compliance, limit flow rate and material constants included in
      the tube law largely depend on the longitudinal stretching ratio. Compared with
      the control group, the tracheal compliance of asthmatic animals decreases
      significantly, which results in an increased limit flow rate. Histological
      studies indicate that asthma can lead to hyperplasia/hypertrophy of smooth muscle
      cells, and increase elastin and collagen fibres in the muscular membrane. Though
      decreasing compliance increases stability, during the onset of asthma, limit flow
      rate is much smaller due to the lower transmural pressure. Asthma leads to a
      stiffer trachea and the obtained results reveal some aspects relevant to asthma
      induced tracheal remodelling.

PMID- 18815757
TI  - Highly efficient transformation of intact yeast-like conidium cells of Tremella
      fuciformis by electroporation.
AB  - Tremella fuciformis is one of higher basidiomycetes. Its basidiospore can
      reproduce yeast-like conidia, also called the blastospore by budding. The yeast
      like conidia of T. fuciformis is monokaryotic and easy to culture by submerged
      fermentation similar to yeast. So it is a good recipient cell for exogenous gene
      expression. In this study, two expression vectors pGlg-gfp containing gpd-Gl
      promoter and gfp gene and pGlg-hph containing gpd-Gl promoter and hph gene were
      constructed. The lowest sensitive concentration of hygromycin for the blastospore
      was determined on three types of media. Our experiments showed that the lowest
      sensitive concentration of hygromycin for the blastospore was 5 microg/mL on MA
      medium. The intact blastospores were transformed with the expression vector pGlg
      hph by electroporation. The putative transformants were obtained by the MA
      selective medium. Experimental results showed that the most effective parameters
      for the electroporation of intact blastospores were obtained by using STM buffer,
      1.0x10(8) cells/mL of blastospores, 200 microL in transformation volume, 6 microg
      plasmid, 2.0 kV/cm of electric pulse voltage, stillness culturing on MB liquid
      medium for 48 h after electroporation. In these transformation conditions, the
      efficiency reached 277 colonies/microg DNA. Co-transformation of plasmid pGlg-gfp
      and pGlg-hph with ratio of 1:1 was performed by electroporation with the optimal
      parameters. The putative co-transformants were obtained by the MA selective
      medium. Eight randomly selected colonies from the vast putative co-transformants
      were analyzed by PCR detection and Southern blotting. The experiments showed that
      the gfp was integrated into the genomes of three transformants. The co
      transformation efficiency was 37.5%. Green fluorescence was observed under laser
      scanning confocal microscope in these gfp positive transformants. This indicates
      that the exogenous gfp can be expressed effectively in the yeast-like conidia of
      T. fuciformis.

PMID- 18815758
TI  - Antibacterial, antifungal and cytotoxic activity of terrestrial cyanobacterial
      strains from Serbia.
AB  - Cyanobacteria are known to be a rich source of biologically active compounds some
      of which can have pharmaceutical importance. In this work we present the
      screening results of cyanobacterial strains for their antibacterial, antifungal,
      and cytotoxic activity. Cyanobacterial strains were isolated from various soil
      types in province of Vojvodina and Central Serbia, Republic of Serbia. The
      screening included 9 strains of Anabaena and 9 strains of Nostoc. Both,
      extracellular products (from the culture liquid) and cellular crude lipophilic
      extracts were tested against 13 bacterial strains and 8 fungal strains. Cytotoxic
      activity was tested against three human cell lines. Methanol extracts were
      prepared according to Ostensvik. Antibacterial and antifungal activities were
      determined measuring inhibition zone, 48 h after inoculation. The cytotoxic
      activity was determined by sulforhodamine B (SRB) colorimetric assay. Of all
      cyanobacterial strains tested, 52% showed some antifungal and 41% antibacterial
      activity. Two out of six tested strains possessed cytotoxic activity. The
      cytotoxic activity of Anabaena strain S12 was found both in culture liquid and
      crude cell extract. It occurred specifically between the 21st and 42nd day of
      cultivation against HeLa and MCF7 cells, but had no activity against cell line
      derived from a healthy tissue. A high percentage of the active strains among the
      tested strains justify the effort of screening cyanobacteria that are isolated
      from terrestrial environments. The most promising strains for the further study
      are Anabaena strain S12 which showed strong cytotoxic and antibacterial activity
      and Anabaena strain S20 which produces a potent antifungal compound. The future
      work, besides further screening and chemical identification of the active
      compounds, should also include the development of culture techniques that would
      lead to more efficient production of biologically active compounds.

PMID- 18815759
TI  - Long-term protection effects of National Reserve to forest vegetation in 4
      decades: biodiversity change analysis of major forest types in Changbai Mountain
      Nature Reserve, China.
AB  - The Changbai Mountain Nature Reserve (CNR) was established in 1960 to protect the
      virgin Korean pine mixed hardwood forest, a typical temperate forest of northeast
      China. We conducted systematic studies of vascular diversity patterns on the
      north slope of the CNR mountainside forests (800-1700 m a.s.l.) in 1963 and 2006
      respectively. The aim of this comparison is to assess the long-term effects of
      the protection on plant biodiversity of CNR during the interval 43 years. The
      research was carried out in three types of forests: mixed coniferous and broad
      leaved forest (MCBF), mixed coniferous forest (MCF), and sub-alpine coniferous
      forest (SCF), characterized by different dominant species. The alpha diversity
      indicted by species richness and the Shannon-Wiener index were found different in
      the same elevations and forest types during the 43-year interval. The floral
      composition and the diversity of vascular species were generally similar along
      altitudinal gradients before and after the 43-year interval, but some substantial
      changes were evident with the altitude gradient. In the tree layers, the dominant
      species in 2006 were similar to those of 1963, though diversity declined with
      altitude. The indices in the three forest types did not differ significantly
      between 1963 and 2006, and these values even increased in the MCBF and MCF from
      1963 to 2006. However, originally dominant species, P. koraiensis for example,
      tended to decline, while the proportion of broad-leaved trees increased, and the
      species turnover in the succession layers trended to shift to higher altitudes.
      The diversity pattern of the under canopy fluctuated along the altitudinal
      gradient due to micro-environmental variations. Comparison of the alpha diversity
      in the three forests shows that the diversity of the shrub and herb layer
      decreased with time. During the process of survey, we also found some rare and
      medicinal species disappeared. Analysis indicates that the changes of the
      diversity pattern in this region are caused by both nature and human factors.
      Meteorological records revealed that climate has changed significantly in the
      past 43 years. We also found the most severe human disturbance to the CNR forests
      in the process of another field survey that is the exploitation of herb medicines
      and Korean pine nuts. We hope this research would give some guidance to the
      future reserve management in Changbai Mountain area.

PMID- 18815760
TI  - [Exudate capacity of modern wound dressings during compression therapy for
      chronic venous leg ulcers].
AB  - Major components in the conservative treatment of patients with chronic venous
      leg ulcers are compression therapy and modern wound dressings. Both therapies are
      used simultaneously. Consequently it is important to know the exudate capacity of
      modern wound dressings changes during compression therapy. In the first part of
      our study we analyzed the maximum exudate capacity of 15 modern wound dressings.
      In the second part we showed that under compression stockings of class 2, a
      reduction of 44.08% and under compression stockings of class 3, a reduction of
      50.49% occurred. In the third part we pointed out that all the investigated wound
      dressings released absorbed fluid when under compression. Again the effect was
      higher when using compression class 3 with 40.78% compared to compression class 2
      with 40.50%. Our results show for the first time the broad variability of exudate
      capacity of modern wound dressings. Our results show that compression therapy has
      a considerable effect on the ability of modern wound dressings to absorb and
      retain exudate and suggests that more frequent changes may be required.

PMID- 18815762
TI  - [Thromboembolic events, abortions and a sick infant--unusual presentation of a
      vitamin deficiency].
AB  - Homocysteine is a risk factor for the development of thromboembolic disorders and
      vascular diseases. Furthermore, complications during pregnancy have been ascribed
      to hyperhomocysteinemia. We report on a pregnant woman being substituted by high
      doses folic acid for hyperhomocysteinemia. Thereby, the underlying pernicious
      anemia was masked. After birth, the neonate was exclusively breastfed. At the age
      of 5 months, the infant had to be admitted to hospital due to severe vitamin
      B(12)-deficiency. Using parenteral vitamin B(12) substitution, homocystein levels
      of the mother normalized and the infant throve and prospered again.

PMID- 18815763
TI  - [A 78-year-old woman suffering from diarrhea, abnormal fatigue, and depression].
AB  - A 78-year-old woman was admitted with diarrhea, abnormal fatigue, and depression.
      Routine diagnostic tests were to a large extent without pathological findings.
      Suppressed TSH was initially considered as subclinical hyperthyreosis because of
      substitution with L-thyroxin. The endocrinological diagnostics showed
      hypopituitarism because of an empty sella. After substitution with hydrocortisone
      and adapted L-thyroxin the patient recovered promptly. Diarrhea, abnormal
      fatigue, and depression might be hints for hypopituitarism with hypocortisolism.

PMID- 18815764
TI  - [Endoscopic asthma therapy. Sense and nonsense].
AB  - In this review a new therapeutic procedure, named bronchial thermoplasty, for
      patients suffering from asthma will be discussed. The technology targets the
      smooth airway muscles, which play an important role especially during an acute
      asthma attack. By means of thermal energy the muscles are destroyed and the
      contractility minimized. Initial studies demonstrated the effectiveness of this
      new approach; in particular, the number of symptom-free days or the frequency of
      exacerbation could be positively influenced. However, a short-term increase in
      morbidity due to bronchoscopy is to be expected. Further trials are needed to
      investigate the value of this method, particularly with regard to long-term
      effects.

PMID- 18815765
TI  - [Forensic radiology].
AB  - Forensic radiology includes both clinical and postmortem forensic radiology.
      Clinical forensic radiology deals with imaging of healthy people from a legal
      point of view, such as for determining age or to prove and document injuries in
      victims of crime. Postmortem forensic radiology deals with the application of
      modern radiological methods in order to optimise post-mortem diagnosis. X-ray
      examination has for decades been routinely used in postmortem diagnosis. Newer
      developments include the application of postmortem computer tomography and
      magnetic resonance imaging; these are the methods with the greatest information
      potential but also with the greatest deviations from diagnostics in living
      persons. Application of radiological methods for securing evidence in criminal
      procedures is still in its infancy. Radiologists' technical understanding and
      forensic doctors' knowledge of postmortem changes in a corpse must be synergised.

PMID- 18815766
TI  - Quantitative trait loci for non-race-specific, high-temperature adult-plant
      resistance to stripe rust in wheat cultivar Express.
AB  - Wheat cultivar Express has durable, high-temperature adult-plant (HTAP)
      resistance to stripe rust (Puccinia striiformis f. sp. tritici). To elucidate the
      genetic basis of the resistance, Express was crossed with 'Avocet Susceptible'
      (AVS). A mapping population of 146 F(5) recombinant inbred lines (RILs) was
      developed using single-seed descent. The RILs were evaluated at two sites near
      Pullman in eastern Washington and one site near Mount Vernon in western
      Washington in 2005, and were evaluated near Pullman in 2006 under natural stripe
      rust infection of predominant races virulent on seedlings of Express. Infection
      type (IT) and disease severity (DS) were recorded three times for each line
      during each growing season. The DS data were used to calculate relative area
      under the disease progress curve (rAUDPC) values. Both IT and rAUDPC data showed
      continuous distributions, indicating that the Express HTAP resistance was
      controlled by quantitative trait loci (QTL). Resistance gene analog polymorphism
      (RGAP) and simple sequence repeat (SSR) techniques were used to map the HTAP
      resistance QTL. Three QTL were detected with significant additive effects,
      explaining 49.5-69.6% of the phenotypic variation for rAUDPC. Two of the QTL
      explained 30.8-42.7% of the phenotypic variation for IT. The three QTL were
      mapped to wheat chromosomes 6AS, 3BL and 1BL, and were designated as QYrex.wgp
      6AS, QYrex.wgp-3BL and QYrex.wgp-1BL, respectively. QYrex.wgp-6AS and QYrex.wgp
      3BL, which had higher effects than QYrex.wgp-1BL, were different from previously
      reported QTL/genes for adult-plant resistance. Markers Xgwm334-Xwgp56 and Xgwm299
      Xwgp66 flanking the two major QTL were highly polymorphic in various wheat
      genotypes, suggesting that these markers are useful in marker-assisted selection.

PMID- 18815767
TI  - Identification of differentially expressed proteins between hybrid and parents in
      wheat (Triticum aestivum L.) seedling leaves.
AB  - In spite of commercial use of heterosis in agriculture, the molecular basis of
      heterosis is poorly understood. To gain a better understanding of the molecular
      basis of wheat heterosis, we carried out a comparative proteomic analysis in
      seedling leaves between wheat hybrid and parents. Common wheat (Triticum aestivum
      L., 2n = 6x = 42, AABBDD) Line 3338 and spelt wheat (Triticum spelta L., 2n = 6x
      = 42, AABBDD) Line 2463 were used to produce a heterotic F(1) hybrid. The
      expression patterns of the total proteins were compared in seedling leaves
      between hybrid and its parents by using two-dimensional gel electrophoresis with
      two pH ranges for the first dimension separation. Among ~900 protein spots
      reproducibly detected, 49 protein spots were identified as being differentially
      expressed between hybrid and its parental lines (P < 0.05) for more than 1.5
      folds. Six possible modes of differential expression were observed, including
      high- and low-parent dominance, underdominance, and overdominance, uniparent
      silencing and uniparent dominance. Moreover, 30 of the 49 differentially
      expressed protein spots were identified, which were involved in metabolism,
      signal transduction, energy, cell growth and division, disease and defense,
      secondary metabolism. These results indicated that wheat hybridization can cause
      protein expression differences between hybrid and its parents; these proteins
      were involved in diverse physiological process pathways, which might be
      responsible for the observed heterosis.

PMID- 18815768
TI  - Analysis of a diverse global Pisum sp. collection and comparison to a Chinese
      local P. sativum collection with microsatellite markers.
AB  - Twenty-one informative microsatellite loci were used to assess and compare the
      genetic diversity among Pisum genotypes sourced from within and outside China.
      The Chinese germplasm comprised 1243 P. sativum genotypes from 28 provinces and
      this was compared to 774 P. sativum genotypes that represented a globally diverse
      germplasm collection, as well as 103 genotypes from related Pisum species. The
      Chinese P. sativum germplasm was found to contain genotypes genetically distinct
      from the global gene pool sourced outside China. The Chinese spring type
      genotypes were separate from the global gene pool and from the other main Chinese
      gene pool of winter types. The distinct Chinese spring gene pool comprised
      genotypes from Inner Mongolia and Sha'anxi provinces, with those from Sha'anxi
      showing the greatest diversity. The other main gene pool within China included
      both spring types from other northern provinces and winter types from central and
      southern China, plus some accessions from Inner Mongolia and Sha'anxi. A core
      collection of Chinese landraces chosen to represent molecular diversity was
      compared both to the wider Chinese collection and to a geographically diverse
      core collection of Chinese landraces. The average gene diversity and allelic
      richness per locus of both the micro-satellite based core and the wider
      collection were similar, and greater than the geographically diverse core. The
      genetic diversity of P. sativum within China appears to be quite different to
      that detected in the global gene pool, including the presence of several rare
      alleles, and may be a useful source of allelic variation for both major gene and
      quantitative traits.

PMID- 18815769
TI  - The Danish National Diabetes Register: trends in incidence, prevalence and
      mortality.
AB  - AIMS/HYPOTHESIS: The aim of the study was to describe trends in the incidence
      rate, prevalence and mortality rate for diabetes in Denmark. METHODS: Healthcare
      registers at the National Board of Health were used to compile a register of
      diabetic patients in the Danish population (5.4 million people). Age- and sex
      specific prevalence, incidence rates, mortality rates and standardised mortality
      ratios relative to the non-diabetic part of the population were calculated.
      RESULTS: The register contains records for about 360,000 persons with diabetes;
      230,000 were alive at 1 January 2007, corresponding to an overall prevalence of
      4.2%. The prevalence increased by 6% per year. In 2004 the incidence rates were
      1.8 per 100,000 at age 40 years and 10.0 per 100,000 at age 70 years. The
      incidence rate increased 5% per year before 2004 and then stabilised. The
      mortality rate in the diabetic population decreased 4% per year, compared with 2%
      per year in the non-diabetic part of the population. The mortality rate decreased
      40% during the first 3 years after inclusion in the register. The standardised
      mortality ratio decreased with age, from 4.0 at age 50 years to 2.5 at age 70
      years and just under 2 at age 85 years, identically for men and women. The
      standardised mortality ratio decreased 1% per calendar year. The lifetime risk of
      diabetes was 30%. CONCLUSIONS/INTERPRETATION: The prevalence of diabetes in
      Denmark rose in 1995-2006, but the mortality rate in diabetic patients decreased
      faster than that of the non-diabetic population. The mortality rate decreased
      markedly just after inclusion in the register. Incidence rates have shown a
      tendency to decrease during the last few years, but this finding should be viewed
      with caution.

PMID- 18815770
TI  - Adaptive support ventilation is a patented technology.

PMID- 18815771
TI  - The use of Fluoro-Jade in primary neuronal cell cultures.
AB  - Fluoro-Jade (FJ) and its derivatives are widely used for histological staining of
      neurons undergoing neurodegeneration. With this dye, the entire structure of
      these neurons can be stained in a fast and reliable way in histopathological
      slices of the brain, with results comparable to those obtained with other methods
      such as the Nissle technique or silver staining. The question arose as to whether
      this method might be useful for in vitro neuronal cell cultures. Primary cortical
      neuronal cell cultures have been used as a sensitive and reliable system to
      detect compounds which induce neurodegenerative lesions (Schmuck et al. 2000).
      Additionally, various biochemical endpoints in this system allow the mode of
      action of these compounds to be identified. The target mechanism of FJ staining
      is unknown, and it may therefore be useful to compare FJ staining with one of the
      central endpoints in compound-induced neurodegeneration, interaction with the
      cytoskeleton as demonstrated by accumulations of neurofilaments (200 kD).
      Cortical neuronal cells were cultivated under standardized serum-free conditions.
      Once they had developed a stable network, the cells were treated with acrylamide,
      mipafox, diethyldithiocarbamate, glutamate, paraquat, paraoxon, and IDPN (ss,ss
      imino dipropionitrile) for 7 days in the concentration range of 0.1-50 microg/ml.
      One half of the cell culture samples were tested directly after 7 days, the
      others were allowed to recover during a 7-day treatment-free period. Subsequently
      viability testing and quantification for FJ staining were performed. All
      compounds except paraoxon increased FJ staining after 7 days, and this signal
      increased slightly during the recovery period with glutamate and acrylamide. With
      mipafox and IDPN the signal decreased slightly. Paraoxon increased FJ staining
      only after the recovery period. The intensity of FJ staining did not always
      correlate with neurofilament destruction or cytotoxicity. It can therefore be
      assumed that FJ targets a different cellular endpoint. Interestingly, paraoxon, a
      compound which does not induce neurodegeneration, increased FJ staining only in
      the recovery phase; this pointed to a neurotoxic mechanism which sets it apart
      from the other model compounds.

PMID- 18815772
TI  - Positive effects of nicotine on cognition: the deployment of attention for
      prospective memory.
AB  - RATIONALE: Human and animal studies over the last two decades report that
      nicotine can improve cognitive performance. Prospective memory (PM), the
      retrieval and implementation of a previously encoded intention, is also improved
      by pre-administration of nicotine. As with other nicotine effects, however,
      predicting precisely how and when nicotine improves the processes engaged by PM
      has proved less straightforward. OBJECTIVE: We present two studies that explore
      the source of nicotine's enhancement of PM. Experiment 1 tests for effects of
      nicotine on preparatory attention (PA) for PM target detection. Experiment 2 asks
      whether nicotine enhances processing of the perceptual attributes of the PM
      targets. MATERIALS AND METHODS: Young adult non-smokers matched on baseline
      performance measures received either 1 mg nicotine or matched placebo via nasal
      spray. Volunteers completed novel PM tasks at 15 min post-administration.
      RESULTS: Experiment 1 confirmed that pre-administration of nicotine to non
      smokers improved detection rate for prospective memory targets presented during
      an attention-demanding ongoing task. There was no relationship between PM
      performance and measures of preparatory attention. In experiment 2, salient
      targets were more likely to be detected than non-salient targets, but nicotine
      did not confer any additional advantage to salient targets. CONCLUSION: The
      present study suggests that nicotinic stimulation does not work to enhance
      perceptual salience of target stimuli (experiment 2), nor does it work through
      better deployment of preparatory working attention (experiment 1). An alternative
      explanation that nicotine promotes PM detection by facilitating disengagement
      from the ongoing task is suggested as a future line of investigation.

PMID- 18815773
TI  - The determination of glutathione-4-hydroxynonenal (GSHNE), E-4-hydroxynonenal
      (HNE), and E-1-hydroxynon-2-en-4-one (HNO) in mouse liver tissue by LC-ESI-MS.
AB  - Glutathione (GSH) conjugation of 4-hydroxy-2(E)-nonenal (HNE) is an efficient
      means of cellular detoxification. HNE is a byproduct of lipid peroxidation which
      has shown toxicity but also signaling roles. E-1-hydroxynon-2-en-4-one (HNO) is
      another byproduct of lipid peroxidation which has the same molecular weight as
      HNE. This study presents the LC-MS detection of GS-HNE, HNE, and HNO in tissue
      samples without derivatization and with minimal sample preparation. Tissue
      samples were taken from wild-type mice and knock-out mice, which have been bred
      without the RLIP76 transfer protein. Extraction procedures were developed to
      determine GS-HNE and HNE levels in the mouse liver tissue. A gradient elution LC
      MS method was developed for GS-HNE analysis using electrospray ionization and
      selected ion monitoring (SIM). The HNE/HNO method involves isocratic elution due
      to instability issues. Higher levels of GSHNE, HNE, and HNO were found in the
      knock-out animals, due to the absence of the RLIP76 transport mechanism.

PMID- 18815774
TI  - fMR-adaptation reveals separate processing regions for the perception of form and
      texture in the human ventral stream.
AB  - We recently demonstrated that attending to the form of objects and attending to
      their surface properties activated anatomically distinct regions of occipito
      temporal cortex (Cant and Goodale, Cereb Cortex 17:713-731, 2007). Specifically,
      attending to form activated the lateral occipital area (LO), whereas attending to
      texture activated the collateral sulcus (CoS). Although these regions showed
      preferential activation to one particular stimulus dimension (e.g. texture in
      CoS), they also showed activation to other, non-preferred stimulus dimensions
      (e.g. form in CoS). This raises the question as to whether the activation
      associated with attention to form in CoS, for example, represents the actual
      processing of object form or instead represents the obligatory processing of
      object texture that occurred when people attended to form. To investigate this,
      we conducted an fMR-adaptation experiment which allowed us to examine the
      response properties of regions specialized for processing form, texture, and
      colour when participants were not explicitly attending to a particular stimulus
      dimension. Participants passively viewed blocks where only one dimension varied
      and blocks where no dimensions varied, while fixating a cross in the centre of
      the display. Area LO was most sensitive to variations in form, whereas the CoS
      was most sensitive to variations in texture. As in our previous study, no regions
      were found that were most sensitive to variations in colour, but unlike the
      results from that study, medial regions of the ventral stream along the fusiform
      gyrus and CoS showed some selectivity to colour. Taken together, these results
      replicate the findings from our previous study and provide additional evidence
      for the existence of separate processing pathways for form and surface properties
      (particularly texture) in the ventral stream.

PMID- 18815775
TI  - Effects of cerebellar TMS on motor cortex of patients with focal dystonia: a
      preliminary report.
AB  - Recent evidence suggests a role for cerebellum in pathophysiology of dystonia.
      Here we explored, the cerebellar modulation of motor cortex in patients with
      focal upper limb dystonia. Eight patients and eight controls underwent a
      transcranial magnetic stimulation protocol to study the cerebellar-brain
      inhibition (CBI): a conditioning cerebellar stimulus (CCS) was followed 5 ms
      after by the contralateral motor cortex stimulation (test stimulus: TS). We
      explored the effects of CBI on MEP amplitude, short intracortical inhibition
      (SICI) and intracortical facilitation (ICF) measures. At baseline no differences
      in TS-MEP amplitude, SICI or ICF were found between patients and controls.
      Cerebellar-conditioning significantly reduced TS-MEP amplitude, increased ICF,
      and decreased SICI in control subjects. In contrast, no changes in these
      neurophysiological measures were observed in the motor cortex of patients,
      regardless of which side was tested. If further confirmed, these findings suggest
      a reduced cerebellar modulation of motor cortex excitability in patients with
      focal dystonia.

PMID- 18815776
TI  - Unconscious perception of a flash can trigger line motion illusion.
AB  - When a flash of light precedes a static line segment, an illusory motion
      sensation is observed with the line propagating away from the flash's location
      towards the opposite side (Hikosaka et al. in Vision Res 33:1219-1240, 1993).
      Here we report that a similar illusory motion percept can be triggered by a non
      consciously perceived flash. Observers reported illusory line motion (ILM)
      arising from the flash's location when a stationary line was presented and the
      flash was not detected. The results imply that the line motion illusion does not
      depend on conscious awareness of the flash and suggest that processing of
      unconscious information can modulate the responses of the neural mechanisms
      involved in motion perception.

PMID- 18815777
TI  - Cytochrome P450 and gene activation--cholesterol elimination and regression of
      atherosclerosis: author reply to the commentary.

PMID- 18815778
TI  - Hajdu-Cheney syndrome associated with serpentine fibulae and polycystic kidney
      disease.
AB  - Six patients who presented with craniofacial anomalies, musculoskeletal anomalies
      including elongated and bowed (serpentine) fibulae, and polycystic kidneys are
      reported. This association of anomalies is referred to as serpentine fibula
      polycystic kidney syndrome (SFPKS) and is currently interpreted as a
      manifestation of Hajdu-Cheney syndrome (HCS). We report a new instance of this
      association of anomalies and review the clinical and radiographic features of HCS
      and of the reported cases of SFPKS.

PMID- 18815779
TI  - Infracardiac total anomalous pulmonary venous return (TAPVR).

PMID- 18815780
TI  - Primary hypothyroidism mimicking a pituitary macroadenoma: regression after
      thyroid hormone replacement therapy.
AB  - We report a 9-year-old girl with pituitary hyperplasia due to primary
      hypothyroidism. She presented with growth arrest, abnormal thyroid function
      studies, and a pituitary mass on MRI. With thyroxine therapy, the pituitary mass
      regressed and her symptoms resolved. Primary hypothyroidism should be considered
      in the differential diagnosis of solid mass lesions of the pituitary gland.

PMID- 18815781
TI  - Functional expression of porcine aminoacylase 1 in E. coli using a codon
      optimized synthetic gene and molecular chaperones.
AB  - Efficient recombinant expression of N-acyl-L-aminoacylase 1 from pig kidney
      (pAcy1) was achieved in the prokaryotic host Escherichia coli. An optimized
      nucleotide sequence (codon adaptation index 0.95 for E. coli), was cloned into
      vector pET-52(b) yielding an E. coli-expressible pAcy1 gene. Formation of
      inclusion bodies was alleviated by co-expression of molecular chaperones
      resulting in 2.7- and 4.2-fold increased recovery of active pAcy1 using trigger
      factor or GroEL-GroES, respectively. Facile purification was achieved via
      StrepTag affinity chromatography. Overall, more than 80 mg highly active pAcy1
      (94 U/mg) was obtained per liter of cultivation broth. The protein was analyzed
      for structural and functional identity, and the performances of further described
      expression and purification systems for pAcy1 were compared.

PMID- 18815782
TI  - Enantioselective resolution of 2-(1-hydroxy-3-butenyl)-5-methylfuran by
      immobilized lipase.
AB  - An efficient and convenient strategy for synthesis of enantiomerically pure S-2
      (1-hydroxy-3-butenyl)-5-methylfuran was for the first time described utilizing a
      lipase-mediated asymmetric acylation in organic solvents. Rhizopus arrhizus
      lipase was chosen as the biocatalyst, and different immobilization methods
      including sol-gel encapsulation and covalent attachment were adopted to improve
      its catalytic characteristics. Various influential factors of the reaction were
      also investigated. Finally, the results showed that the lipase covalently
      attached onto epoxy resin exhibited the highest enantioselectivity and
      operational stability. Under optimized reaction conditions, i.e., n-hexane as the
      solvent, 5/1 (mol/mol) of vinyl acetate to 2-(1-hydroxy-3-butenyl)-5-methylfuran
      and 30 degrees C, the ee value of S-1 reached up to above 98% at 52% conversion
      with an E value of 99.

PMID- 18815783
TI  - A dormancy state in nonspore-forming bacteria.
AB  - While cultivation is a convenient way of proliferating and understanding
      bacteria, studies have shown the formation of nonculturable cells in nonspore
      forming bacteria in response to environmental stress and thus in turn have
      generated immense interest. Whether these cells are in a state of dormancy or in
      a stage preceding cell death has been considered of paramount importance for the
      past couple of decades. In this study, osmotic-stress-induced dormant bacterial
      cells were separated by cell sorting and revived by osmotic down-shift in the
      absence of nutrients, source(s) that potentially could supply nutrients, and/or
      the external addition of resuscitation factor(s). Reversal of dormancy followed a
      definite pattern akin to population asynchrony of dormant cells, and the
      phenomenon was observed across three species, namely, Enterobacter sp. strain
      mcp11b, Klebsiella pneumonia strain mcp11d and Escherichia coli. In addition, our
      study precisely forecasted the presence of multiple subpopulations in dormant
      cells, which is explained by an emerging theory of survival mechanisms in
      stressful environments. These observations reveal that the state of dormancy
      induced by environmental stress in these nonspore-forming bacteria is
      "reversible" and also implies that it is an orderly and spontaneous adaptation to
      circumvent adverse conditions.

PMID- 18815784
TI  - Hydroxylation of naphthalene by aromatic peroxygenase from Agrocybe aegerita
      proceeds via oxygen transfer from H2O2 and intermediary epoxidation.
AB  - Agrocybe aegerita peroxidase/peroxygenase (AaP) is an extracellular fungal
      biocatalyst that selectively hydroxylates the aromatic ring of naphthalene. Under
      alkaline conditions, the reaction proceeds via the formation of an intermediary
      product with a molecular mass of 144 and a characteristic UV absorption spectrum
      (A(max) 210, 267, and 303 nm). The compound was semistable at pH 9 but
      spontaneously hydrolyzed under acidic conditions (pH<7) into 1-naphthol as major
      product and traces of 2-naphthol. Based on these findings and literature data, we
      propose naphthalene 1,2-oxide as the primary product of AaP-catalyzed oxygenation
      of naphthalene. Using (18)O-labeled hydrogen peroxide, the origin of the oxygen
      atom transferred to naphthalene was proved to be the peroxide that acts both as
      oxidant (primary electron acceptor) and oxygen source.

PMID- 18815785
TI  - Low-dose radiation enhances therapeutic HPV DNA vaccination in tumor-bearing
      hosts.
AB  - Current therapeutic approaches to treatment of patients with bulky cervical
      cancer are based on conventional in situ ablative modalities including cisplatin
      based chemotherapy and radiation therapy. The 5-year survival of patients with
      nonresectable disease is dismal. Because over 99% of squamous cervical cancer is
      caused by persistent infection with an oncogenic strain of human papillomavirus
      (HPV), particularly type 16 and viral oncoproteins E6 and E7 are functionally
      required for disease initiation and persistence, HPV-targeted immune strategies
      present a compelling opportunity in which to demonstrate proof of principle.
      Sublethal doses of radiation and chemotherapeutic agents have been shown to have
      synergistic effect in combination with either vaccination against cancer-specific
      antigens, or with passive transfer of tumor-specific cytotoxic T lymphocytes
      (CTLs). Here, we explored the combination of low-dose radiation therapy with DNA
      vaccination with calreticulin (CRT) linked to the mutated form of HPV-16 E7
      antigen (E7(detox)), CRT/E7(detox) in the treatment of E7-expressing TC-1 tumors.
      We observed that TC-1 tumor-bearing mice treated with radiotherapy combined with
      CRT/E7(detox) DNA vaccination generated significant therapeutic antitumor effects
      and the highest frequency of E7-specific CD8(+) T cells in the tumors and spleens
      of treated mice. Furthermore, treatment with radiotherapy was shown to render the
      TC-1 tumor cells more susceptible to lysis by E7-specific CTLs. In addition, we
      observed that treatment with radiotherapy during the second DNA vaccination
      generated the highest frequency of E7-specific CD8(+) T cells in the tumors and
      spleens of TC-1 tumor-bearing mice. Finally, TC-1 tumor-bearing mice treated with
      the chemotherapy in combination with radiation and CRT/E7(detox) DNA vaccination
      generate significantly enhanced therapeutic antitumor effects. The clinical
      implications of the study are discussed.

PMID- 18815786
TI  - A mathematical model for brain tumor response to radiation therapy.
AB  - Gliomas are highly invasive primary brain tumors, accounting for nearly 50% of
      all brain tumors (Alvord and Shaw in The pathology of the aging human nervous
      system. Lea & Febiger, Philadelphia, pp 210-281, 1991). Their aggressive growth
      leads to short life expectancies, as well as a fairly algorithmic approach to
      treatment: diagnostic magnetic resonance image (MRI) followed by biopsy or
      surgical resection with accompanying second MRI, external beam radiation therapy
      concurrent with and followed by chemotherapy, with MRIs conducted at various
      times during treatment as prescribed by the physician. Swanson et al. (Harpold et
      al. in J Neuropathol Exp Neurol 66:1-9, 2007) have shown that the defining and
      essential characteristics of gliomas in terms of net rates of proliferation (rho)
      and invasion (D) can be determined from serial MRIs of individual patients. We
      present an extension to Swanson's reaction-diffusion model to include the effects
      of radiation therapy using the classic linear-quadratic radiobiological model
      (Hall in Radiobiology for the radiologist. Lippincott, Philadelphia, pp 478-480,
      1994) for radiation efficacy, along with an investigation of response to various
      therapy schedules and dose distributions on a virtual tumor (Swanson et al. in
      AACR annual meeting, Los Angeles, 2007).

PMID- 18815787
TI  - Expression analysis of a plum pathogenesis related 10 (PR10) protein during brown
      rot infection.
AB  - Plant PR10 is one of the pathogenesis related proteins, induced upon exposure to
      different stress conditions including fungal infection. PR10 proteins have been
      implicated in fungal disease resistance in some species; however its
      transcriptional regulation is not well understood. In the present work we cloned
      a PR10 gene from European plums (Prunus domestica L.) and monitored the
      quantitative changes in its transcript levels as a result of fungal infection in
      two varieties. We also studied the possible involvement of the membrane degrading
      enzyme phospholipase D-alpha (PLDalpha). In the susceptible variety, 'Veeblue',
      infection with the brown rot fungus Monilinia fructicola induced PLDalpha and
      PR10 expression, while in the resistant variety, 'Violette', a constitutive
      expression of PLDalpha and PR10 transcripts levels were observed. Resistance to
      M. fructicola also coincides with a sharp decrease in the expression of ABI1, a
      protein phosphatase and elevated hydrogen peroxide content after infection.
      Further, inhibition of PLDalpha by hexanal treatment, up-regulated ABI1 and
      decreased PR10 expression, suggesting a possible relationship between the two. We
      further confirm these results in Arabidopsis abi1 mutant that shows a higher
      level of PR10 transcripts.

PMID- 18815788
TI  - The marker SCK13(603) associated with resistance to ascochyta blight in chickpea
      is located in a region of a putative retrotransposon.
AB  - The sequence characterized amplified region (SCAR) marker SCK13(603), associated
      with ascochyta blight resistance in a chickpea recombinant inbred line (RIL)
      population, was used as anchored sequence for genome walking. The PCRs performed
      in the walking steps to walk in the same direction produced eight bands in 5'
      direction and five bands in 3' direction with a length ranking from 530 to 2,871
      bp. The assembly of the bands sequences along with the sequence of SCK13(603)
      resulted in 7,815 bp contig. Blastn analyses showed stretches of DNA sequence
      mainly distributed from the nucleotides 1,500 to 4,500 significantly similar to
      Medicago truncatula genomic DNA. Three open reading frames (ORFs) were identified
      and blastp analysis of predicted amino acids sequences revealed that ORF1, ORF2
      and ORF3 had significant similarity to a CCHC zinc finger protein, to an
      integrase, and to a precursor of the glucoamylase s1/s2, respectively, from M.
      truncatula. The high homology of the putative proteins derived from ORF1 and ORF2
      with retrotransposon proteins and the prediction of the existence of conserved
      domains usually present in retrotransposon proteins indicate that the marker
      SCK13(603) is located in a region of a putative retrotransposon. The information
      generated in this study has contributed to increase the knowledge of this
      important region for blight resistance in chickpea.

PMID- 18815789
TI  - Tumour and tumour-like lesions of the patella--a multicentre experience.
AB  - Fifty-nine cases of lesions presenting in the patella were identified after
      review of the databases of four European bone tumour registries. Of the 59 cases,
      46% were non neoplastic, 39% were benign and 15% were malignant. The commonest
      benign neoplasm was giant cell tumour (GCT) (11 cases). Younger patients were
      more likely to have a benign neoplasm. Lesions in patients less than 40 years of
      age included giant cell tumour, chondroblastoma, aneurysmal bone cyst (ABC),
      osteomyelitis, osteoid osteoma and solitary bone cyst. In patients older than 40
      years, the following were common lesions: intra-osseous gout, metastasis and
      intra-osseous ganglion. Expansion of the patella with thinning of cortex was seen
      more commonly in GCT and brown tumour in hyperparathyroidism. There was
      associated soft tissue extension in gout and malignant lesions.

PMID- 18815790
TI  - The added diagnostic value of 64-row multidetector CT combined with contrast
      enhanced US in the evaluation of hepatocellular nodule vascularity: implications
      in the diagnosis of malignancy in patients with liver cirrhosis.
AB  - The aim of this study was to assess the added diagnostic value of contrast
      enhanced US (CEUS) combined with 64-row multidetector CT (CT) in the assessment
      of hepatocellular nodule vascularity in patients with liver cirrhosis. One
      hundred and six cirrhotic patients (68 male, 38 female; mean age +/- SD, 70 +/- 7
      years) with 121 biopsy-proven hepatocellular nodules (72 hepatocellular
      carcinomas, 10 dysplastic and 15 regenerative nodules, 12 hemangiomas, and 12
      other benignancies) detected during US surveillance were prospectively recruited.
      Each nodule was scanned by CEUS during the arterial (10-40 s), portal venous (45
      90 s), and delayed sinusoidal phase (from 100 s after microbubble injection to
      microbubble disappearance). Nodule vascularity at CEUS, CT, and combined CEUS/CT
      was evaluated side-by-side by two independent blinded readers who classified
      nodules as benign or malignant according to reference diagnostic criteria. The
      combined assessment of CEUS/CT provided higher sensitivity (97%, both readers)
      than did separate assessment of CEUS (88% reader 1; 87% reader 2) and CT (74%
      reader 1; 71% reader 2; P < 0.05), while no change in specificity was provided by
      combined analysis. The combined assessment of hepatocellular nodule vascularity
      at CT and CEUS improved sensitivity in the diagnosis of malignancy in patients
      with liver cirrhosis.

PMID- 18815791
TI  - US examination of the appendix in children with suspected appendicitis: the
      additional value of secondary signs.
AB  - This study evaluated the additional value of secondary signs in the diagnosing of
      appendicitis in children with ultrasound. From May 2005 to June 2006, 212
      consecutive paediatric patients with suspected appendicitis were examined.
      Ultrasonographic depiction of the appendix was classified into four groups: 1,
      normal appendix; 2, appendix not depicted, no secondary signs of appendicitis; 3,
      appendix not depicted with one of the following secondary signs: hyperechoic
      mesenteric fat, fluid collection, local dilated small bowel loop; 4, depiction of
      inflamed appendix. We classified 96 patients in group 1, 41 in group 2, 13 in
      group 3, and 62 in group 4. Prevalence of appendicitis was 71/212 (34%). Negative
      predictive values of groups 1 and 2 were 99% and 100%, respectively. Positive
      predictive values of groups 3 and 4 were 85% and 95%, respectively. In groups 3
      and 4, hyperechoic mesenteric fat was seen in 73/75 (97.3%), fluid collections
      and dilated bowel loops were seen in 12/75 (16.0%) and 5/75 (6.6%), respectively.
      This study shows that in case of non-visualization of the appendix without
      secondary signs, appendicitis can be safely ruled out. Furthermore, secondary
      signs of appendicitis alone are a strong indicator of acute appendicitis.

PMID- 18815792
TI  - [Light exposition in vitreoretinal surgery. I. Basics].
AB  - Due to its function of light perception, the eye is exposed to high levels of
      radiation of the optical spectrum. Most of the ultraviolet and infrared radiation
      is absorbed in the cornea and lens, and mostly only radiation of the visible
      spectrum can reach the retina. Visible light can cause retinal damage by
      photomechanical, photothermal, and photochemical mechanisms. The most important
      mechanism of light damage to the retina under daily conditions or when using
      ophthalmologic light sources is the photochemical light toxicity caused by light
      induced chemical reactions. The extent of damage depends on several factors, such
      as wavelength, exposure time, and irradiance. Particularly the shorter portion of
      the visible light spectrum (blue light) is responsible for photochemical damage
      to the retina.

PMID- 18815794
TI  - Survival and metabolism of Rana arvalis during freezing.
AB  - Freeze tolerance and changes in metabolism during freezing were investigated in
      the moor frog (Rana arvalis) under laboratory conditions. The data show for the
      first time a well-developed freeze tolerance in juveniles of a European frog
      capable of surviving a freezing exposure of about 72 h with a final body
      temperature of -3 degrees C. A biochemical analysis showed an increase in liver
      and muscle glucose in response to freezing (respectively, 14-fold and 4-fold
      between 4 and -1 degrees C). Lactate accumulation was only observed in the liver
      (4.1+/-0.8 against 16.6+/-2.4 micromol g(-1) fresh weight (FW) between 4 and -1
      degrees C). The quantification of the respiratory metabolism of frozen frogs
      showed that the aerobic metabolism persists under freezing conditions (1.4+/-0.7
      microl O(2) g(-1) FW h(-1) at -4 degrees C) and decreases with body temperature.
      After thawing, the oxygen consumption rose rapidly during the first hour (6-fold
      to 16-fold) and continued to increase for 24 h, but at a lower rate. In early
      winter, juvenile R. arvalis held in an outdoor enclosure were observed to emerge
      from ponds and hibernate in the upper soil and litter layers. Temperature
      recordings in the substratum of the enclosure suggested that the hibernacula of
      these juvenile frogs provided sheltering from sub-zero air temperatures and
      reduced the time spent in a frozen state corresponding well with the observed
      freeze tolerance of the juveniles. This study strongly suggests that freeze
      tolerance of R. arvalis is an adaptive trait necessary for winter survival.

PMID- 18815795
TI  - Cerebrospinal fluid levels of interleukin-6 and interleukin-12 in children with
      meningitis.
AB  - PURPOSE: Certain cytokines play important roles in the pathophysiology of
      meningitis. The main purpose of this study was to investigate if the levels of
      interleukin-6 (IL-6) and interleukin-12 (IL-12) in cerebrospinal fluid (CSF)
      could be diagnostic predictors of bacterial meningitis in children. METHODS: CSF
      was obtained from 95 patients suspected with meningitis. These cases were
      classified to the bacterial meningitis (n = 12), aseptic meningitis (n = 41), and
      nonmeningitis (n = 42) groups. The levels of IL-6 and IL-12 in CSF were measured
      using the enzyme-linked immmunosorbent assays test. RESULTS: The CSF IL-6 levels
      in the bacterial meningitis group (45.2 +/- 50.0 pg/ml) were significantly higher
      than those in the aseptic meningitis group (12.9 +/- 10.2 pg/ml) and the
      nonmeningitis group (6.5 +/- 7.8 pg/ml; p < 0.05). The CSF IL-12 levels in the
      bacterial meningitis group (69.8 +/- 67.1 pg/ml) were significantly higher than
      those in the aseptic meningitis group (22.9 +/- 10.8 pg/ml) and the nonmeningitis
      group (15.3 +/- 11.2 pg/ml; p < 0.05). With regard to diagnosis, the measurement
      of CSF IL-6 and IL-12 levels showed sensitivities of 96% and 96%, respectively,
      and specificities of 51% and 75%, respectively. CONCLUSION: It is suggested that
      the CSF IL-6 and IL-12 levels are useful markers for distinguishing bacterial
      meningitis from aseptic meningitis.

PMID- 18815796
TI  - The "creeping fat sign"-really diagnostic for Crohn's disease?
AB  - BACKGROUND: Focal or regionally prominent mesenteric fat adjacent to wall
      thickened bowel loops can be readily identified by computed tomography. The so
      called creeping fat of the right lower quadrant is usually considered to be an
      important clue for diagnosing Crohn's disease. However, when the sign is
      isolated, indistinct, and not set in the proper clinical context, the radiologist
      should consider other inflammatory conditions of the bowel and its appendages.
      CONCLUSION: Controlled studies are needed to confirm the diagnostic use of the
      "creeping fat sign" in clinical practice.

PMID- 18815797
TI  - Selective reduction of Von Economo neuron number in agenesis of the corpus
      callosum.
AB  - Von Economo neurons (VENs) are large spindle-shaped neurons localized to anterior
      cingulate cortex (ACC) and fronto-insular cortex (FI). VENs appear late in
      development in humans, are a recent phylogenetic specialization, and are
      selectively destroyed in frontotemporal dementia, a disease which profoundly
      disrupts social functioning and self-awareness. Agenesis of the corpus callosum
      (AgCC) is a congenital disorder that can have significant effects on social and
      emotional behaviors, including alexithymia, difficulty intuiting the emotional
      states of others, and deficits in self- and social-awareness that can impair
      humor, comprehension of non-literal or affective language, and social judgment.
      To test the hypothesis that VEN number is selectively reduced in AgCC, we used
      stereology to obtain unbiased estimates of total neuron number and VEN number in
      postmortem brain specimens of four normal adult controls, two adults with
      isolated callosal dysgenesis, and one adult whose corpus callosum and ACC were
      severely atrophied due to a non-fatal cerebral arterial infarction. The partial
      agenesis case had approximately half as many VENs as did the four normal
      controls, both in ACC and FI. In the complete agenesis case the VENs were almost
      entirely absent. The percentage of neurons in FI that are VENs was reduced in
      callosal agenesis, but was actually slightly above normal in the stroke patient.
      These results indicate that the VEN population is selectively reduced in AgCC,
      but that the VENs do not depend on having an intact corpus callosum. We conclude
      that in agenesis of the corpus callosum the reduction in the number of VENs is
      not the direct result of the failure of this structure to develop, but may
      instead be another consequence of the genetic disruption that caused the
      agenesis. The reduction of the VEN population could help to explain some of the
      social and emotional deficits that are seen in this disorder.

PMID- 18815798
TI  - Reconstruction of the articular surface of the humeral head after locked
      posterior shoulder dislocation: a case report.
AB  - Posterior dislocations of the glenohumeral joint are extremely rare (2-4% of all
      shoulder dislocations) and often associated with bone or ligamentary injuries.
      Though the reverse Hill-Sachs lesion is a common injury associated with posterior
      shoulder dislocation, there have been only few articles describing specific
      treatments for this type of humeral head defect. This article describes the
      successful operative treatment of an acute locked posterior shoulder dislocation
      by reconstructing the articular surface of the humeral head with the use of
      autologous bone graft taken from the iliac crest. The patient was doing quite
      well with no complaints, good range of shoulder motion and no recurrence of
      posterior shoulder dislocation despite several epileptic seizures, 1.5 years
      after surgical reconstruction of the anatomy of the humeral head. His right
      shoulder function revealed to be "excellent" or "good", assessed with an absolute
      Constant Score of 76 points and a relative Score of 88% when compared with an age
      and sex-matched normal population.

PMID- 18815799
TI  - Porous-coated femoral components with or without hydroxyapatite in primary
      uncemented total hip arthroplasty: a systematic review of randomized controlled
      trials.
AB  - The purpose of this systematic review was to determine the clinical and
      radiologic benefit of hydroxyapatite coating in uncemented primary total hip
      arthroplasty. A database of Medline articles published up to September 2007 was
      compiled and screened. Eight studies involving 857 patients were included in the
      review. Pooled analysis for Harris hip score as a clinical outcome measure
      demonstrated no advantage of the hydroxyapatite coating (WMD: 1.49, P = 0.44).
      Radiologically, both groups showed equal presence of endosteal bone ingrowth (RR:
      1.04, P = 0.66) and radioactive lines (RR: 1.02, P = 0.74) in the surface area of
      the prosthesis. This meta-analysis demonstrates neither clinical nor radiologic
      benefits on the application of a hydroxyapatite coating on a femoral component in
      uncemented primary total hip arthroplasty.

PMID- 18815800
TI  - Prediction and prevention of autoimmune skin disorders.
AB  - Autoimmune diseases can be preceded by a symptom-free phase which is defined by
      the presence of autoantibodies, and may last for many years. These autoantibodies
      may have a high positive predictive value for disease onset, severity and organ
      specific complications, especially in genetically prone individuals.
      Characteristic autoantibodies and susceptible genes have been identified in many
      autoimmune systemic and mucocutaneous diseases such as systemic lupus
      erythematosus, pemphigus, vitiligo, dermatitis hepretiformis and even psoriasis.
      Prevention of overt disease may be achieved once high-risk individuals are
      identified and triggering factors are avoided. Numerous environmental factors,
      such as vitamin D deficiency, ultraviolet light, smoking, drugs, etc., that may
      trigger autoimmunity have been found. Alternatively, even if the autoimmune
      disease cannot be prevented, it may be postponed or attenuated. Thus, although
      large body of evidence has accumulated on characteristic autoantibodies,
      susceptible genes and environmental factors, many more large scale studies are
      needed to assess their predictive value, the preventive measurements and the
      means to apply them to clinical management of healthy population and high-risk
      individuals.

PMID- 18815801
TI  - Pregnancy outcomes in women complicated by thalassemia syndrome at Maharaj Nakorn
      Chiang Mai Hospital.
AB  - OBJECTIVE: To determine the maternal and fetal outcomes of women complicated with
      thalassemia syndrome. STUDY DESIGN: Retrospective descriptive study. MATERIALS
      AND METHODS: The database of Maternal-Fetal Medicine unit and medical records,
      between January 2001 and April 2008, were reviewed to search for pregnant women
      complicated with thalassemia syndrome and medical records were reviewed for
      patient's baseline characteristics and pregnancy outcomes. The inclusion criteria
      consisted of (1) pregnant women diagnosed for thalassemia syndrome by
      hematologist either during or before pregnancy based on hemoglobin typing, (2)
      attending the antenatal care clinic and delivery at Maharaj Nakorn Chiang Mai
      hospital, and (3) available data of pregnancy outcomes. RESULTS: During the study
      period, 80 pregnant women with thalassemia syndrome were recruited, including 52
      (65%) cases of HbH disease, 23 (28.8%) cases of beta-thalassemia/HbE disease, 2
      cases of AE Bart's disease, 2 cases of EF Bart's disease and 1 case of beta
      thalassemia major. Excluding 2 twin pregnancies and 1 case with beta-thalassemia
      major, 77 were available for analysis of the outcomes. The mean gestational age
      (+/-SD) at delivery was 37.40 (+/-2.6) weeks, range 27-42 weeks. Twenty-five
      (32.5%) had delivery by cesarean section and the remainder had successful vaginal
      delivery. Fetal growth restriction was found in 21 cases (27.3%), 16 (20.8%) had
      preterm births and the rate of low birth weight (<2,500 g) was 44.1%. Regard to
      the type of thalassemia, baseline hemoglobin levels and mean birth weight of
      women with beta-thal/Hb E was significantly lower than the levels of those with
      Hb H disease. CONCLUSION: This series indicates that, in spite of an attempt to
      keep hemoglobin levels above 7.0 g/dl, pregnancy with thalassemia is likely to be
      associated with an increased rate of fetal growth restriction, preterm birth and
      low birth weight.

PMID- 18815802
TI  - The association of lymph node volume with cervical metastatic lesions in head and
      neck cancer patients.
AB  - The aim of this study was to determine if volume of cervical lymph node measured
      via computed tomography (CT) could differentiate metastatic from benign lesions
      in head and neck cancer patients. We conducted a retrospective review of chart
      and images in a tertiary referring center in Taiwan. Patients with head and neck
      cancers underwent radical, modified radical or functional neck dissection were
      enrolled. The CT images before operation were reassessed by a radiologist and
      were compared with the results of pathological examination. A total of 102
      patients were included for final analyses. Most patients were male (n = 96, 94%)
      and average age was 50.1 years. Although the average nodal volume in patients
      with cervical metastases was higher than those of patients without cervical
      metastases, it was not an independent factor associated with cervical metastasis
      after controlling for other variables; however, central nodal necrosis on
      enhanced CT image [odds ratio (OR) 18.95, P = 0.008) and minimal axial diameter
      >7.5 mm (OR 6.868, P = 0.001) were independent factors correlated with cervical
      metastasis. Therefore, the volume of cervical lymph node measured from CT images
      cannot predict cervical metastases in head and neck cancer patients. Measurement
      of minimal axial diameter of the largest lymph node is a simple and more accurate
      way to predict cervical metastasis instead.

PMID- 18815803
TI  - Upregulation of Semaphorin 3A and the associated biochemical and cellular events
      in a rat model of retinal detachment.
AB  - BACKGROUND: Retinal detachment, as a result of injury or disease, is a severe
      disorder that may ultimately lead to complete blindness. Despite advanced
      surgical repair techniques, the visual acuity of patients is often limited. We
      investigated some of the biochemical and morphological alterations following
      experimental retinal detachment in laboratory animals. METHODS: Unilateral
      retinal detachment was induced in male Wistar rats; contralateral untreated eyes
      served as a control. Approximately half of the retinal area was detached by a sub
      retinal injection of 5 mul Saline. The incidence and extent of the retinal
      detachment was evaluated using MRI analysis and fundus images. The retinas were
      collected at intervals of 24 hours, 7, 14 and 28 days following the procedure.
      Using Western blot and immunohistochemical analysis, the expression levels of
      Semaphorin3A, Neuropilin1, GAP43 and NF-H were studied. In addition,
      morphological changes in Muller and microglial cells were examined. TUNEL
      staining was used to assess apoptosis. RESULTS: We found that the expression
      level of Semaphorin3A was up-regulated and reached its peak at two time points:
      24 hours and 14 days after surgery. A similar pattern of expression was found for
      Neuropilin1. TUNEL-positive cells, indicating apoptotic processes, were evident
      24 hours post retinal detachment and increased after 7 days. On the other hand,
      GAP43 expression was up-regulated 14 days after retinal detachment, and further
      intensified 28 days post-surgery. Microglial cells were activated shortly after
      detachment and concentrated mostly at the inner plexiform layer. GFAP staining
      revealed hypertrophy of Muller cells. CONCLUSIONS: The biochemical and
      morphological changes suggest that apoptosis as well as axonal regrowth take
      place following retinal detachment. Collectively, these findings may explain the
      limited success following repair surgery in terms of visual acuity and
      physiological function of the retina. Our study may open a new approach for
      treatment of early phase retinal detachment, as well as improve post-operative
      care that may, in turn, improve the functional result of the surgery. In
      addition, further study is required on several other factors that may affect
      visual acuity, such as size and location of the detached area and the time lapse
      between detachment and surgery.

PMID- 18815804
TI  - Short-term hypoxia reduces arterial stiffness in healthy men.
AB  - This study examined the effects of hypoxia (80% arterial oxyhaemoglobin
      saturation for 20 min) and the accompanying changes in heart rate and blood
      pressure on two components of arterial stiffness in healthy men. Augmentation
      index (AIx) and time to reflection (Tr) representing measures of muscular artery
      and aortic stiffness, respectively, were continuously measured. At first,
      subjects were exposed to either hypoxia (n = 12) or room air (n = 5). During
      early hypoxia AIx increased by 6% before decreasing to baseline. After hypoxia
      AIx decreased by a further 6%. In contrast there was no change in Tr. Six
      subjects were then exposed to hypoxia following infusion with the nitric oxide
      (NO) synthase inhibitor NG-mono-methyl-L: -arginine (L-NMMA) or saline. During
      hypoxia AIx decreased by 12% following saline but increased by 14% after L-NMMA
      and Tr did not change. These findings suggest that hypoxia may induce NO-mediated
      vasodilatation of small muscular arteries but not the aorta.

PMID- 18815805
TI  - Identification of soybean microRNAs and their targets.
AB  - The microRNAs (miRNAs) are a newly identified class of small non-protein-coding
      regulatory RNA. Using comparative genomics, we identified 69 miRNAs belonging to
      33 families in the domesticated soybean (Glycine max) as well as five miRNAs in
      the soybean wild species Glycine soja and Glycine clandestine. TaqMan((R))
      MicroRNA Assay analyses demonstrated that these miRNAs were differentially
      expressed in soybean tissues, with certain classes expressed preferentially in
      both a spatiotemporal and a tissue-specific manner. Detailed sequence analyses
      revealed that soybean pre-miRNAs vary in length from 44 to 259 nt with an average
      of 106 +/- 45 nt, harbor mature miRNAs that differ in their physical location
      within the pre-miRNAs, and encode more than a single mature miRNA. Comparative
      sequence analyses of soybean miRNA sequences showed that uracil is the dominant
      base in the first position at the 5' end of the mature miRNAs while cytosine is
      dominant at the 19th position, which is indicative that these two bases may have
      an important functional role in miRNA biogenesis and/or miRNA-mediated gene
      regulation. Soybeans were unique among plants in the frequency of occurrence of
      miRNA clusters. For the first time, antisense miRNAs were identified in plants.
      The five antisense miRNAs and their sense partners from soybean belonged to three
      miRNA families (miR-157, miR-162 and miR-396). Antisense miRNAs were also
      identified in soybean wild species. Mature antisense miRNA products appeared to
      have 1-3 nucleotide changes compared to their sense partners, which suggests that
      both strands of a miRNA gene can produce functional mature miRNAs and that
      antisense transcripts may differ functionally from their sense partners. Based on
      previously established in silico methods, we predicted 152 miRNA-targeted mRNAs,
      which included a large percentage of mRNAs that encode transcription factors that
      regulate plant growth and development as well as a lesser percentage of mRNAs
      that encode environmental signal transduction proteins and central metabolic
      processes.

PMID- 18815806
TI  - Nuclear hormone receptor signaling in amphioxus.
AB  - The nuclear hormone receptors (NRs) form a superfamily of transcription factors
      unified by conserved protein structure and mode of function. While most members
      of this superfamily are activated by ligands, such as thyroid hormones, steroids,
      vitamin D or retinoic acid, other NRs are called orphan receptors because they
      have no known ligand. NR-dependent signaling is crucial for vertebrate
      development with the majority of receptors being expressed in the developing
      embryo. Due to massive gene duplications during vertebrate diversification, there
      are usually more NRs in vertebrates than in invertebrates. In this study, we
      examine the evolutionary diversification of the NR superfamily and of NR
      dependent signaling in chordates (vertebrates, tunicates, and amphioxus). We take
      advantage of the unique features of the genome of the invertebrate amphioxus,
      which is characterized by a vertebrate-like gene content without having undergone
      massive duplications, to assess the NR signaling complement (NRs and NR
      coregulators) of the ancestral chordate. We find 33 NRs in amphioxus, which are
      more NRs than originally anticipated. This increase is mainly due to an amphioxus
      specific duplication of genes encoding receptors of the NR1H group. In addition,
      there are three heterologous NRs in amphioxus that could not be placed within the
      framework of the NR superfamily. Apart from these exceptions, there is usually
      one amphioxus NR or NR signaling coregulator for each paralogous group of two,
      three, or four human receptors suggesting that the ancestral chordate had a set
      of 22 different NRs plus one copy of each NR coregulator.

PMID- 18815807
TI  - Conservation of linkage and evolution of developmental function within the
      Tbx2/3/4/5 subfamily of T-box genes: implications for the origin of vertebrate
      limbs.
AB  - T-box genes encode a family of DNA-binding transcription factors implicated in
      numerous developmental processes in all metazoans. The Tbx2/3/4/5 subfamily genes
      are especially interesting because of their key roles in the evolution of
      vertebrate appendages, eyes, and the heart, and, like the Hox genes, the
      longevity of their chromosomal linkage. A BAC library derived from the single
      male amphioxus (Branchiostoma floridae) used to sequence the amphioxus genome was
      screened for AmphiTbx2/3 and AmphiTbx4/5, yielding two independent clones
      containing both genes. Using comparative expression, genomic linkage, and
      phylogenetic analyses, we have reconstructed the evolutionary histories of these
      members of the T-box gene family. We find that the Tbx2-Tbx4 and Tbx3-Tbx5 gene
      pairs have maintained tight linkage in most animal lineages since their birth by
      tandem duplication, long before the divergence of protostomes and deuterostomes
      (e.g., arthropods and vertebrates) at least 600 million years ago, and possibly
      before the divergence of poriferans and cnidarians (e.g., sponges and jellyfish).
      Interestingly, we find that the gene linkage detected in all vertebrate genomes
      has been maintained in the primitively appendage-lacking, basal chordate,
      amphioxus. Although all four genes have been involved in the evolution of
      developmental programs regulating paired fin and (later) limb outgrowth and
      patterning, and most are also implicated in eye and heart development, linkage
      maintenance--often considered due to regulatory constraints imposed by limb, eye,
      and/or heart associated gene expression--is undoubtedly a consequence of other,
      much more ancient functional constraints.

PMID- 18815808
TI  - Implantable cardioverter defibrillator as a bridge to recovery in an infant with
      cardiac rhabdomyoma.
AB  - Multiple cardiac rhabdomyomas in an infant presented with recurrent life
      threatening ventricular arrhythmias refractory to medical treatment and
      necessitating the placement of an implantable cardioverter defibrillator (ICD).
      The device functioned effectively as a bridge to recovery during a 2-year follow
      up period, when the tumor showed spontaneous regression, along with an almost
      complete resolution of the ventricular arrhythmias. We conclude that childhood
      cardiac rhabdomyomas causing severe drug-refractory ventricular arrhythmias can
      be managed by ICD therapy.

PMID- 18815809
TI  - Quality assessment of clinical practice guidelines for the prevention and
      treatment of childhood overweight and obesity.
AB  - BACKGROUND: The prevalence of childhood overweight and obesity is increasing at
      dramatic rates in children and adolescents worldwide. Clinical practice
      guidelines (CPGs) are "systematically developed statements to assist practitioner
      and patient decisions about appropriate health care for specific clinical
      circumstances." Their objective is to provide explicit recommendations for
      clinical practice based on current evidence for best practice in the management
      of diseases. MATERIALS AND METHODS: The aim of this study was to identify and
      assess the quality of CPGs for the prevention and treatment of obesity and
      overweight in childhood. We developed a search to identify CPGs published between
      January 1998 and August 2007. We considered for inclusion documents that provided
      recommendations for clinical practice referring to children and adolescents.
      Three independent appraisers assessed the quality of the1 CPGs using the AGREE
      (Appraisal of Guidelines Research and Evaluation) instrument. We identified 376
      references and selected 22 for further assessment. RESULTS: The overall agreement
      among reviewers using the intraclass correlation coefficient was 0.856 (95%
      confidence interval [CI] 0.731-0.932). Six of the 22 initial guidelines were
      recommended and a further eight were recommended with conditions or provisos. We
      concluded that the number of documents with recommendations on the prevention and
      treatment of childhood obesity published during the 10-year study period was
      considerable, but only a few of them could be considered as high quality. CPGs
      were deficient in areas such as applicability, editorial independence and rigor
      in development. CONCLUSION: Due to the increasing burden of obesity among
      children and the potential for long-term comorbidities, clinicians need to be
      critical in assessing the rigor of how these are developed and their
      appropriateness for use in the clinician's own practice. There is a need to
      improve the methodology and the quality of CPGs on childhood obesity to help
      clinicians and other decision-makers to tackle this disease.

PMID- 18815810
TI  - Reference genes for quantitative analysis on Clonorchis sinensis gene expression
      by real-time PCR.
AB  - The accuracies of relative gene expressions as determined by quantitative real
      time polymerase chain reaction are largely dependent on the variabilities of the
      reference genes used. Validation of the stabilities of reference genes under
      experimental conditions is an essential initial step for comparative studies on
      the expression levels of target genes in experimental groups. Using three total
      RNA samples extracted independently from Clonorchis sinensis metacercariae and
      adults, we determined the gene expression stabilities of eight reference gene
      candidates and the relative transcript levels of three target genes using the
      geNorm program. The reference genes found to be stably expressed in metacercariae
      and adults were phosphoglycerate kinase, beta-actin, and calcyphosine; reference
      genes found to be stably expressed under gamma-irradiated and non-irradiated
      conditions were succinate dehydrogenase, small nuclear ribonucleoprotein, and
      beta-actin; and those stably expressed regardless of bile treatment were small
      nuclear ribonucleoprotein, phosphoglycerate kinase, and succinate dehydrogenase.
      According to our data, the expression levels of target genes are dependent on
      normalization factors, such as the C (T) values of single reference genes and the
      geometric mean of the C (T) values of three reference genes. When comparing C.
      sinensis gene expressions, we propose to employ the geometric mean of the C (T)
      values of more than three reference genes validated in the same experimental
      setting.

PMID- 18815811
TI  - Dynamic development of parasitophorous vacuole of Eimeria tenella transfected
      with the yellow fluorescent protein gene fused to different signal sequences from
      apicomplexan parasites.
AB  - Intracellular stages of Eimeria tenella reside within a membrane-bound
      parasitophorous vacuole (PV). PVs of apicomplexan parasites like E. tenella play
      important roles in nutrient acquisition, multiplication, and evasion of host
      immune responses. Different signal sequences from apicomplexan parasites were
      investigated in the transfected E. tenella for their functions in targeting
      yellow fluorescent protein (YFP) to subcompartments and the dynamic development
      of the PV of E. tenella was studied. Two 5' terminal signal sequences derived
      from Toxoplasma gondii GRA8 protein and Plasmodium falciparum repetitive
      interspersed family protein, respectively, were confirmed to target YFP to the
      PVs of the transfected E. tenella, suggesting that signal sequences are
      functionally conserved among Apicomplexa. Three structurally different types of
      PVs were observed during the endogenous development of the transfected E. tenella
      in vitro. In addition, three subcompartments in the PV, namely, membranous
      extensions into the host cell cytosol, membranous extensions into the vacuolar
      lumen, and particle-like bodies, were detected during schizogony of the parasite.

PMID- 18815812
TI  - Src family kinases as mediators of endothelial permeability: effects on
      inflammation and metastasis.
AB  - Src family kinases (SFKs) are signaling enzymes that have long been recognized to
      regulate critical cellular processes such as proliferation, survival, migration,
      and metastasis. Recently, considerable work has elucidated mechanisms by which
      SFKs regulate normal and pathologic processes in vascular biology, including
      endothelial cell proliferation and permeability. Further, when inappropriately
      activated, SFKs promote pathologic inflammatory processes and tumor metastasis,
      in part through their effects on the regulation of endothelial monolayer
      permeability. In this review, we discuss the roles of aberrantly activated SFKs
      in mediating endothelial permeability in the context of inflammatory states and
      tumor cell metastasis. We further summarize recent efforts to translate Src
      specific inhibitors into therapy for systemic inflammatory conditions and
      numerous solid organ cancers.

PMID- 18815814
TI  - The concurrent presentation of minimal change nephrotic syndrome and aplastic
      anemia.
AB  - Minimal change nephrotic syndrome (MCNS) has been associated with primary
      immunological disorders, such as lymphoma and thymoma. While several different
      explanations have been proposed, much of the literature has implicated activated
      T-lymphocytes in the pathogenesis. We report a patient with minimal change
      nephrotic syndrome presenting concurrently with thrombocytopenia and anemia, with
      a subsequent diagnosis of aplastic anemia. To our knowledge, this is the first
      such case described in the literature.

PMID- 18815815
TI  - Kidney growth in children with congenital hypothyroidism.
AB  - The effect of hypothyroidism on kidney size has not been studied in children. The
      aim of this study was to examine the role of congenital hypothyroidism and
      levothyroxine (L-thyroxine) treatment on renal growth. Forty children with
      congenital hypothyroidism and 37 healthy controls were prospectively included.
      The mean age of patients was 8.2+/-4.7 years. Patients had lower height and
      weight standard deviation scores compared with controls. The mean L-thyroxine
      initial age and treatment duration were 37.0 and 60.5 months, respectively. In
      62.5% of patients, L-thyroxine was initiated after 6 months of age, and 60.0% of
      patients had severe hypothyroidism. Patients had lower kidney length and total
      kidney volume compared with controls (P < 0.05). No significant differences were
      found in kidney volume/body weight and kidney volume/ body height ratios between
      patients and controls (P > 0.05). Multiple regression analysis showed significant
      relationship between relative kidney volume and average free thyroxine level (P <
      0.05). No significant differences in kidney sizes were found between patients who
      had L-thyroxine initiated before and after 6 months of age or between
      mild/moderate and severe hypothyroidism at diagnosis (P > 0.05). In conclusion,
      normal renal growth can be accomplished with L-thyroxine replacement despite
      considerable delay in treatment initiation and/or severe hypothyroidism.

PMID- 18815813
TI  - Targeted delivery of therapeutics to endothelium.
AB  - The endothelium is a target for therapeutic and diagnostic interventions in a
      plethora of human disease conditions including ischemia, inflammation, edema,
      oxidative stress, thrombosis and hemorrhage, and metabolic and oncological
      diseases. Unfortunately, drugs have no affinity to the endothelium, thereby
      limiting the localization, timing, specificity, safety, and effectiveness of
      therapeutic interventions. Molecular determinants on the surface of resting and
      pathologically altered endothelial cells, including cell adhesion molecules,
      peptidases, and receptors involved in endocytosis, can be used for drug delivery
      to the endothelial surface and into intracellular compartments. Drug delivery
      platforms such as protein conjugates, recombinant fusion constructs, targeted
      liposomes, and stealth polymer carriers have been designed to target drugs and
      imaging agents to these determinants. We review endothelial target determinants
      and drug delivery systems, describe parameters that control the binding of drug
      carriers to the endothelium, and provide examples of the endothelial targeting of
      therapeutic enzymes designed for the treatment of acute vascular disorders
      including ischemia, oxidative stress, inflammation, and thrombosis.

PMID- 18815816
TI  - Diagnostic accuracy of urine dipsticks for detecting albuminuria in indigenous
      and non-indigenous children in a community setting.
AB  - Albuminuria predicts cardiovascular and end-stage kidney disease in indigenous
      populations. Early detection in indigenous children may identify those who could
      benefit from early treatment. Community-based detection of albuminuria needs to
      be performed using a reliable, inexpensive, and widely available test, such as a
      proteinuria dipstick. Dipstick accuracy for detecting albuminuria in a community
      setting has not been evaluated. We assessed the accuracy of Multistix 10 SG
      dipsticks to detect baseline albuminuria and predict for persistent albuminuria
      at a 2-year follow-up in a population-based cohort of Australian Aboriginal and
      non-Aboriginal elementary-school-aged children. Variability in the accuracy of
      dipsticks in subgroups of higher risk children was analyzed using the relative
      diagnostic odds ratio (RDOR). Using Multistix 10 SG dipsticks, index-test
      positive cases were defined as >/=0.30 g/L (1+) proteinuria and index-test
      negative cases as <0.30 g/L (negative or trace) proteinuria. Referent-test
      positive cases were defined as spot albumin:creatinine (ACR) >/=3.4 mg/mmol, and
      referent-test-negative cases as ACR <3.4 mg/mmol. There were 2,266 children
      (55.1% Aboriginal, 51.0% boys, mean age 8.9 years) enrolled. At the 2-year follow
      up, 1,432 (63.0%) children were retested (54.0% Aboriginal, 50.5% boys, mean age
      10.5 years). Prevalence of baseline albuminuria was 7.3%, and persistent
      albuminuria was 1.5%. Dipsticks had a sensitivity of 62% and specificity of 97%
      at baseline. In predicting persistent albuminuria, sensitivity was 75% and
      specificity 93%. Accuracy did not vary with ethnicity, gender, or body mass
      index. Accuracy was less in younger children (4.0-7.9 years), and in those with
      hematuria. The performance characteristics of Multistix dipsticks make them
      suitable for albuminuria detection in Aboriginal and other higher-risk groups of
      children. More than two thirds of children detected at a single test will have
      transient rather than persistent albuminuria. Multistix dipsticks are
      particularly useful for detecting children who will have persistent albuminuria.

PMID- 18815817
TI  - Ureteric jet Doppler waveform: is it a reliable predictor of vesicoureteric
      reflux in children?
AB  - The purpose of our prospective study was to find out whether ureteric jet Doppler
      waveform (UJDW) could be a reliable predictor of vesicoureteral reflux (VUR) in
      children, compared with echo-enhanced voiding ultrasonography (VUS). Echo
      enhanced VUS was performed in 75 children, 57 girls and 18 boys, aged 3 years to
      12 years, following the accepted indications for this procedure. During the same
      procedure the measurement of UJDW was also performed and was considered to be
      successful (in 70 children) when at least ten UJDWs were recorded per ureteric
      unit. Depending on the shape of the UJDWs, the sequences were classified into
      three groups: monophasic, suggestive of VUR; complex, not suggestive of VUR; and
      mixed sequence, suggestive of VUR when a certain ratio between monophasic and
      complex UJDWs was achieved. When all three sequences were taken into account, the
      overall sensitivity and specificity of this method in detecting VUR were 88.5%
      and 82.3%, respectively. These values seem high enough for this method to be
      considered as a good alternative to invasive micturating cystographies in
      screening children for VUR.

PMID- 18815818
TI  - Transplanted xenogenic bone marrow stem cells survive and generate new bone
      formation in the posterolateral lumbar spine of non-immunosuppressed rabbits.
AB  - Bone marrow stem cells (BMSCs) are pluripotent cells that have been used to
      facilitate bone repair because of their capability of differentiating into
      osteoblasts. However, it is well known that the number of BMSCs with osteogenic
      potential decreases in patients with old age, osteoporosis, and metabolic
      diseases. In such conditions, xenogenic BMSCs may provide an alternative to
      autologous BMSCs. In the current study, we investigated the potential of
      transplanted xenogenic BMSCs to survive and generate new bone formation in the
      posterolateral lumbar spine of non-immunosuppressed rabbits. The BMSCs were
      obtained from bilateral femurs of four male rats, cultured and expanded in medium
      with osteoinduction supplement. The BMSCs (1,000,000 cells) of male rats loaded
      onto 5 cc compression resistant matrix (CRM; Medtronic Sofamor Danek, USA) were
      implanted bilaterally onto the L4-5 intertransverse processes of 16 female
      rabbits (xenogenic BMSCs + CRM group). The 16 female rabbits that received 5 cc
      CRM alone were used as controls (CRM alone group). To exclude the possibility of
      migration of BMSCs from the transverse processes of the recipient rabbits, we did
      not decorticate the transverse processes. No rabbits received any
      immunosuppressive medications during the experiment. Four rabbits each in both of
      the experimental and control groups were killed at 1, 2, 4, and 6 months
      postimplantation, and the lumbar spine underwent radiological and histological
      analyses for evaluation of new bone formation. The polymerase chain reaction
      (PCR) for Sry gene (Y-chromosome-specific marker) was used to evaluate the
      survival of transplanted xenogenic BMSCs. The expression of Sry gene was clearly
      identified in the lumbar spines of all the 16 rabbits in the xenogenic BMSCs +
      CRM group at 1-6 months postimplantation. Serial plain radiographs showed gradual
      resorption of CRM; however, it was difficult to clearly identify the presence of
      new bone formation due to the radiopacity of the remaining CRM. Histologically,
      mature lamellar and woven bone with osteoblasts and osteocytes were identified in
      all eight rabbits in the xenogenic BMSCs + CRM group at 4 and 6 months
      postimplantation, but in none of the eight rabbits at 1 and 2 months
      postimplantation. None of CRM alone group showed new bone formation at 1-6 months
      postimplantation. Mild-to-moderate infiltration of inflammatory cells was
      identified around the CRM carriers in both the groups. No post-operative wound
      infection was found in either group. Our results indicate that xenogenic BMSCs
      loaded onto CRM survive and generate new bone formation when placed into the
      posterolateral lumbar spine of rabbits without immunosuppression. To determine if
      a solid fusion can be achieved with such techniques, further studies are needed
      to investigate the appropriate dose of xenogenic BMSCs, amounts of CRM, and the
      requisite incubation time.

PMID- 18815819
TI  - NF1 diagnosis criteria and associated sarcomatous tumor review of the literature
      and case report.
AB  - AIM: This paper reports the case of a sarcomatous tumor (probably a pleomorphic
      sarcoma) in a patient with Neurofibromatosis type 1 (NF1) and discusses the
      association between these two diseases. BACKGROUND: NF1 is an autosomal dominant
      tumor predisposition syndrome. Malignant transformation is observed in patients
      with this disease, usually in the form of malignant peripheral nerve sheath
      tumors (MPNSTs). REPORT: A 72-year-old female patient with diagnosis of NF1
      presented with left mandibular region enlarged for about 6 months, intra-oral
      examination revealed a mass growth on the floor of the lower left posterior area
      of the oral cavity measuring 5 cm in its greatest diameter and covered by
      ulcerated mucosa. SUMMARY: Few cases of association of neurofibromatosis with
      other types of soft tissue sarcomas have been reported. Undifferentiated
      pleomorphic sarcomas are the most common of these tumors. We intend to call
      attention to the importance of patient follow-up and counseling.

PMID- 18815820
TI  - Alternaria infectoria brain abscess in a child with chronic granulomatous
      disease.
AB  - In the present report, we describe the first case of a phaeohyphomycotic brain
      abscess in a 5-year-old boy with chronic granulomatous disease (CGD) admitted to
      hospital with seizures. A computed tomography (CT) scan revealed a cerebral
      abscess and the microbiology study showed a dark, melanin-pigmented fungus,
      exhibiting only sterile hyphae. This fungus was identified by the amplification
      and sequencing of the 5.8S RNA gene and of the adjacent internal transcriber
      spacer domains, ITS1 and ITS2, as Alternaria infectoria. Due to the impossibility
      of a surgical excision, and although several therapeutic strategies were
      attempted, the patient died. Limitations in the routine identification procedures
      and therapeutic options of this emerging opportunistic agent are highlighted in
      this report.

PMID- 18815821
TI  - Surgical management of foramen magnum meningiomas.
AB  - The objective of the study is to describe our experience in the surgical
      management of foramen magnum meningiomas with regard to the clinical-radiological
      findings, the surgical approach and the outcomes after mid-term follow up. Over a
      5-year period, 15 patients presenting with meningiomas of the foramen magnum
      underwent surgical treatment. The medical records were reviewed in order to
      analyze the clinical-radiological aspects, as well as the surgical approach and
      the outcomes. Based on the preoperative magnetic resonance imaging exams, the
      tumors were classified as anterior or anterolateral in the axial slices and
      clivospinal or spinoclival in the sagittal slices. The lateral approach was used
      in all cases. However, the extent of bone removal and the management of the
      vertebral artery were tailored to each patient. Fourteen patients were females,
      and one was male, ranging in age from 42 to 74 years (mean 55,9 years). The
      occipital condyle was partially removed in eight patients, and in seven patients,
      removal was not necessary. Total removal of the tumor was achieved in 12
      patients, subtotal in two, and partial resection in one patient. Postoperative
      complications occurred in two patients. Follow-up ranged from 6 to 56 months
      (mean 23.6 months).There was no surgical mortality in this series. The extent of
      the surgical approach to foramen magnum meningiomas must be based on the main
      point of dural attachment and tailored individually case-by-case. The
      differentiation between the clivospinal and spinoclival types, as well as
      anterior and anterolateral types, is crucial for the neurosurgical planning of
      foramen magnum meningiomas.

PMID- 18815822
TI  - Enhanced removal of dimethyl sulfide from a synthetic waste gas stream using a
      bioreactor inoculated with Microbacterium sp. NTUT26 and Pseudomonas putida.
AB  - The removal of dimethyl sulfide (DMS) from industrial gas streams has received a
      high priority due to its very low odorous threshold value and relatively low
      biodegradability compared to other reduced sulfur compounds. A variety of
      bacteria that utilize DMS as a carbon/energy source have been studied and the
      degradation pathway elucidated. However, to date, there have been few reports on
      the industrial application of such bacteria inoculated into a bioreactor for DMS
      treatment. An additional problem of such systems is the accumulation of
      intermediate metabolites that strongly impact on DMS removal by the microbe. The
      results reported here were obtained using a bioreactor inoculated with the H(2)S
      degrader Pseudomonas putida and the DMS-degrader Microbacterium sp. NTUT26 to
      facilitate removal of metabolic intermediates and DMS. This bioreactor performed
      well (1.71 g-S/day/kg-dry packing material) in terms of DMS gas removal, based on
      an evaluation of the apparent kinetics and maximal removal capacity of the
      system. Under varying conditions (changes in start-up, inlet loading, shutdown,
      and re-start), the bioreactor inoculated with Microbacterium sp. NTUT26 and P.
      putida enhanced removal of high concentrations of DMS. Our results suggest that
      this type of bioreactor system has significant potential applications in treating
      (industrial) DMS gas streams.

PMID- 18815823
TI  - Short- and long-term effects of CPAP on upper airway anatomy and collapsibility
      in OSAH.
AB  - RATIONALE AND AIM: In obstructive sleep apnea hypopnea (OSAH) patients, an
      increase of upper airway (UA) collapsibility has been described together with a
      reduced UA caliber due to inflammation, edema, and fat accumulation in pharyngeal
      walls. CPAP is the main treatment of OSAH and acts mechanically by increasing
      pressure inside UA. The aim of this study was to assess the short- and long-term
      effects of CPAP on UA caliber and collapsibility in severe OSAH patients.
      PATIENTS AND METHODS: Ten obese patients (nine male, age 55+/- 9 yr, BMI 35.1 +/-
      6.1, Epworth sleepiness scale 12.3 +/- 3.6 point, AHI 58.8 +/- 27.1) had
      measurements of oropharingeal junction area (OPJ), mean pharyngeal area (APmean),
      maximal pharyngeal area (APmax) by acoustic pharyngometry and determination of
      expired volume in the first 0.5 s after the application at the mouth of -5
      cmH(2)O negative expiratory pressure (V,NEP(0.5)) during wakefulness in the
      supine position under basal conditions (baseline) and after 1 week and 6 months
      of CPAP treatment. RESULTS: OPJ was 0.74 +/- 0.28 cm(2) at baseline, 0.90 +/-
      0.24 cm(2) after 1 week and 1.05 +/- 0.31 cm(2) after 6 months (1 week and 6
      months vs baseline p < 0.05). APmax was 2.28 +/- 0.74 cm(2) at baseline, 2.79 +/-
      0.90 cm(2) after 1 week and 2.94 +/- 0.33 cm(2) after 6 months (1 week and 6
      months vs baseline p < 0.05). APmean was 1.43 +/- 0.46 cm(2) at baseline, 1.82 +/
      0.45 cm(2) after 1 week and 1.94 +/- 0.35 cm(2) after 6 months (1 week vs
      baseline p < 0.01; 6 months vs baseline; p < 0.05). V,NEP(0.5) was 290 +/- 73 mL
      at baseline, 291 +/- 65 mL after 1 week and 338 +/- 67 mL after 6 months (6
      months vs baseline p < 0.05; 1 week vs 6 months p < 0.01). CONCLUSIONS: Our data
      suggest that CPAP treatment might be effective in OSAH patients not only by
      causing a mechanical splint of UA but also by inducing an improvement on
      anatomical (early) and functional (later on) aspects of UA that can be observed
      during wakefulness.

PMID- 18815824
TI  - Habitual and low-impact activities are associated with better bone outcomes and
      lower body fat in older women.
AB  - The influence of habitual and low-impact physical activity (PA) on bone health
      and soft tissue including bone-free lean (BFL) and fat mass is less elucidated
      than the influence of high-impact activities. This study examines the interactive
      effects of PA and soft tissue on bone mineral density (BMD) and content (BMC) in
      healthy Caucasian women, aged 68.6 +/- 7.1 years, with body mass index (BMI) of
      26.0 +/- 3.8 kg/m(2) evaluated at baseline and every 6 months for 3 years.
      Measurements/assessments included BMD/BMC and soft tissue (by dual-energy X-ray
      absorptiometry), anthropometrics, dietary intake, and PA. Activities assessed
      were past activity, present heavy housework, gardening, do-it-yourself
      activities, stair-climbing, walking, walking pace, sports/recreation, and total
      activity. Baseline analyses revealed significant positive associations between
      past activity, heavy housework, faster-paced walking, BFL, and BMD/BMC of various
      skeletal sites. Prospective analyses showed subjects with more walking hours/week
      had significantly higher BMD/BMC of several skeletal sites (P < 0.05).
      Stratification by cumulative (over 3 years) median for heavy housework, walking,
      sports/recreational, and total activities revealed higher BMD and BMC in the
      femur and spine (P = 0.01) in subjects with those activities above median.
      Multivariate analysis of covariance results revealed that weight had the
      strongest influence on BMD and BMC, followed by BFL. Various modes of PA were
      negatively associated with BMI and fat but not with BFL. In conclusion, heavy
      housework, walking (faster pace), sports/recreational activities, and overall
      total participation in low-impact PA were beneficial for bone and for achieving
      more favorable body weight and fat but were not associated with BFL. The results
      indicate that even habitual activities engaged in by older women could benefit
      their bone and diminish body fat.

PMID- 18815825
TI  - Whole-genome duplications in the ancestral vertebrate are detectable in the
      distribution of gene family sizes of tetrapod species.
AB  - A clustering of all protein coding genes from the complete genomes of five
      tetrapod species into gene families shows a clear deviation from the expected
      power-law distribution of gene family size. We hypothesize that at least part of
      the deviation is the result of the two whole-genome duplications (WGDs) that are
      now known, with reasonable certainty, to have occurred prior to the fish-tetrapod
      split. We build a model of homologous gene family evolution and perform
      simulations to show that speciations alone cannot produce a distribution that
      resembles the empirical data. In order to replicate the features of the empirical
      distribution, the simulation must incorporate two WGD events. These WGDs must be
      such that a significant number of the gene duplicates generated in the WGDs have
      a higher retention rate than they do following small-scale duplication (SSD).
      This requirement is consistent with what is known about duplicate retention
      following a WGD, namely, that genes belonging to specific functional classes,
      such as genes regulating transcription, are much more likely to be retained
      following WGD than SSD. We conclude that the deviation from the power-law that we
      observe in the empirical data is the result of the two WGDs that occurred in the
      ancestral chordate. This implies that the two ancient WGDs continue to have a
      structural effect on gene families approximately 500 million years after the
      initial events. On the one hand, this is a surprising result, given the limited
      retention of duplicates generated by a WGD and the continual SSD, which further
      weakens the signal created by the fraction of duplicate pairs that are retained.
      On the other hand, WGD's capacity to fundamentally change the architecture of
      gene families in a profound and lasting way is consistent with the observed
      correlation between WGDs and important evolutionary transitions.

PMID- 18815826
TI  - Fibrous stroma and vascularity of pancreatic carcinoma: correlation with
      enhancement patterns on CT.
AB  - OBJECTIVE: To demonstrate the contrast-enhancement behavior of pancreatic
      carcinoma on dynamic contrast-enhanced CT (DCE-CT), and the relationship between
      the degree of contrast-enhancement and the vascularity (vessel density) and
      amount of fibrous stroma (fibrosis within the tumor) on pathological specimen.
      METHODS: The contrast-enhancement values were measured by producing the
      subtracting images for obtaining largest region of interests to reduce
      measurement errors and variability. Vascularity was determined by immunostaining
      of the tissue sections with factor 8 and the fibrous stroma was determined by
      picrosirius staining. Correlation of the findings of DCE-CT with pathological
      findings was performed in 21 patients with pancreatic carcinoma. RESULTS: All but
      one patient exhibited a gradually increasing enhancement, but there was
      considerably wide range in contrast-enhancement values of tumors. Examination of
      the overall relationship between vascularity and fibrous stroma with contrast
      enhancement behavior showed that tumor with more fibrosis and higher vascularity
      had a higher contrast effect through all phases of dynamic study. Tumors having
      liver metastases tended to be less fibrotic than tumors without liver metastases.
      CONCLUSION: The contrast-enhancement behavior of pancreatic carcinoma may be
      helpful in estimating vascularity and the extent of tumor fibrosis and
      possibility of liver metastases.

PMID- 18815827
TI  - Cumulative industrial activity alters lotic fish assemblages in two boreal forest
      watersheds of Alberta, Canada.
AB  - We evaluated the cumulative effects of land use disturbance resulting from forest
      harvesting, and exploration and extraction of oil and gas resources on the
      occurrence and structure of stream fish assemblages in the Kakwa and Simonette
      watersheds in Alberta, Canada. Logistic regression models showed that the
      occurrence of numerically dominant species in both watersheds was related to two
      metrics defining industrial activity (i.e., percent disturbance and road
      density), in addition to stream wetted width, elevation, reach slope, and percent
      fines. Occurrences of bull trout, slimy sculpin, and white sucker were negatively
      related to percent disturbance and that of Arctic grayling, and mountain
      whitefish were positively related to percent disturbance and road density.
      Assessments of individual sites showed that 76% of the 74 and 46 test sites in
      the Kakwa and Simonette watersheds were possibly impaired or impaired. Impaired
      sites in the Kakwa Watershed supported lower densities of bull trout, mountain
      whitefish, and rainbow trout, but higher densities of Arctic grayling compared to
      appropriate reference sites. Impaired sites in the Simonette Watershed supported
      lower densities of bull trout, but higher densities of lake chub compared to
      reference sites. Our data suggest that current levels of land use disturbance
      alters the occurrence and structure of stream fish assemblages.

PMID- 18815828
TI  - Rights and conflicts in the management of fisheries in the Lower Songkhram River
      Basin, Northeast Thailand.
AB  - A complex, pre-existing local property rights system, characterized by overlap
      and conflict, comprises the local basis for managing inland fisheries in
      communities of the Lower Songkhram River Basin (LSRB) of Northeastern Thailand.
      The components, conflicts and changes of the system are analyzed for fourteen
      communities, focusing on the auction system for barrages, an illegal and
      destructive, yet tolerated, fishery. These rights, adapted to gear type,
      seasonality, and habitat of the LSRB fisheries, are a critical social resource
      and proven management system that should be legitimized. Recommendations are made
      for both improving general inland fisheries policy and reforming the barrage
      fishery.

PMID- 18815829
TI  - Fluorescence spectroscopy as a promising tool for a polyphasic approach to
      pseudomonad taxonomy.
AB  - Fluorescence spectroscopy is an emerging tool for the analysis of biomolecules
      from complex matrices. We explored the potentialities of the method for the
      pseudomonad taxonomic purpose at the genus and species level. Emission spectra of
      three intrinsic fluorophores (namely, NADH, tryptophan, and the complex of
      aromatic amino acids and nucleic acid) were collected from whole bacterial cells.
      Their comparisons were performed through principal component analysis and
      factorial discriminant analysis. Reference strains from the Xanthomonas,
      Stenotrophomonas, Burkholderia, and Pseudomonas genera were well separated, with
      sensitivity and selectivity higher than 90%. At the species level, P. lundensis,
      P. taetrolens, P. fragi, P. chlororaphis, and P. stutzeri were also well
      separated, in a distant group, from P. putida, P. pseudoalcaligenes, and P.
      fluorescens. These results are in agreement with the generally admitted rRNA and
      DNA bacterial homology grouping but they also provide additional information
      about strain relatedness. In the case of environmental isolates, the method
      allows good discrimination, even for strains for which ambiguity still remained
      after PCR and API 20NE identification. Rapid, easy to perform, and low cost,
      fluorescence spectroscopy provides substantial information on cell components.
      Statistical analysis of collected data allows in-depth comparison of strains. Our
      results strongly support the view that fluorescence spectroscopy fingerprinting
      can be used as a powerful tool in a polyphasic approach to pseudomonad taxonomy.

PMID- 18815830
TI  - Biodegradation of chlorpyrifos in soil by enriched cultures.
AB  - Three aerobic bacterial consortia, AC, BC, and DC, developed from pesticide
      contaminated soils of Punjab were able to degrade chlorpyrifos after 21 days of
      incubation in basal medium by 54, 46, and 61% and chlorpyrifos (50 mg/L) in soil
      after 30 days by 50, 56, and 64%. Pseudomonas aeruginosa, Bacillus cereus,
      Klebsiella sp., and Serratia marscecens obtained from these consortia showed 84,
      84, 81, and 80% degradation of chlorpyrifos (50 mg/L) in liquid medium after 20
      days and 92, 60, 56, and 37% degradation of chlorpyrifos (50 mg/L) in soil after
      30 days. Populations of Bacillus cereus, Klebsiella sp., and Serratia marscecens
      remained steady in soil experiments except for P. aeruginosa, where the
      population showed a substantial increase. Formation of 3,5,6-trichloro-2
      pyridinol, the major metabolite of chlorpyrifos degradation, was observed during
      the degradation of chlorpyrifos by P. aeruginosa, which disappeared to negligible
      amounts.

PMID- 18815831
TI  - Effect of the inoculum size on carbapenem susceptibilities of beta-lactamase
      negative, ampicillin-resistant Haemophilus influenzae.
AB  - A higher inoculum size of beta-lactamase-positive Haemophilus influenzae is
      reported to increase minimum inhibitory concentrations (MICs) for beta-lactams.
      However, the effect of inoculum size of beta-lactamase-negative, ampicillin
      resistant H. influenzae (BLNAR) on MICs for carbapenems has not been
      investigated. This study evaluated the effect of inoculum size on MICs for
      carbapenems and other beta-lactams in nine clinical isolates of BLNAR. The MICs
      were determined by both the standard method described by the Clinical and
      Laboratory Standards Institute (final inoculum size of 5 x 10(5) colony-forming
      units [CFU]/ml) and a modified method (final inoculum size of 5 x 10(6) CFU/ml)
      using viable cell counts. The findings showed that the higher inoculum size
      increased MICs for imipenem, meropenem, panipenem, biapenem, ampicillin,
      ceftazidime, and ceftriaxone. The inoculum effect (4 log(2) dilution or a greater
      increase in the MIC) with imipenem, meropenem, panipenem, and biapenem was found
      in three, five, two, and two isolates, respectively. The magnitude of the
      inoculum effect for panipenem significantly increased with the levels of MICs,
      but correlation between them for the others was not statistically significant.
      The mutations of penicillin-binding protein genes had little relevance to the
      reduced susceptibility to carbapenems or to the magnitude of the inoculum effect.
      These results suggest that MIC determination using turbidity can produce
      interpretive errors in the antimicrobial susceptibility testing of BLNAR for
      carbapenems because of their inoculum effect. Thus, accurate adjustment of
      inoculum size, such as viable cell count, is helpful for confirming the true MICs
      when the isolates are interpreted as "resistant" by turbidity-based MIC
      determination.

PMID- 18815832
TI  - The lysis system of the Streptomyces aureofaciens phage mu1/6.
AB  - Previously, two genes, designated as lyt and hol, were identified in the lysis
      module of phage mu1/6. They were cloned and expressed in Escherichia coli. An
      additional candidate holin gene, hol2, was found downstream from the hol gene
      based on one predicted transmembrane domain and a highly charged C-terminal
      sequence of the encoded protein. Expression of hol or hol2 in E. coli was shown
      to cause cell death. The concomitant expression of lambda endolysin (R) and mu1/6
      holin resulted in cell lysis. Similarly, the coexpression of the endolysin and
      holin of phage mu1/6 led to lysis, apparently due to the ability of mu1/6
      endolysin to hydrolyze the peptidoglycan layer of this bacterium. In contrast,
      the simultaneous expression of mu1/6 hol2 and the endolysin gene (lambdaR or
      mu1/6 lyt) did not cause detectable lysis of the host cells. Demonstration of the
      holin function in streptomycetes was achieved by providing for the release of
      mu1/6 endolysin to the periplasm and subsequent cleavage of the peptidoglycan,
      which strongly suggested that the holin produces lesions in the streptomycete
      membrane.

PMID- 18815834
TI  - Heart rate variability and disease characteristics in patients with COPD.
AB  - Heart rate variability (HRV) is reduced in patients with chronic obstructive
      pulmonary disease (COPD). However, the relationships among HRV and
      characteristics of COPD are unknown. The aim of this study was to characterize
      HRV in patients with COPD and to verify the correlation of HRV measured during
      rest with disease severity and pulmonary, muscular, and functional impairment.
      Thirty-one patients with COPD (16 male; 66 +/- 8 years; BMI = 24 +/- 6 kg/m(2);
      FEV(1) = 46 +/- 16% predicted) without severe cardiac dysfunction were included.
      HRV assessment was performed by the head-up tilt test (HUTT), and the main
      variables used for analysis were SDNN index, LF/HF ratio, and R-R intervals.
      Other tests included spirometry, bioelectrical impedance, cardiopulmonary
      exercise test, 6-minute walk test, respiratory and peripheral muscle force,
      health-related quality of life and functional status questionnaires, and
      objective quantification of physical activity level in daily life with the
      DynaPort and SenseWear armband activity monitors, besides calculation of the BODE
      index. There was a statistical difference in all variables of HRV between the
      HUTT positions (lying and standing). There was no correlation of HRV with BODE
      index or FEV(1). Out of the BODE index, just the BMI was correlated with SDNN and
      R-R intervals (r = 0.44; p < 0.05 and r = 0.37; p < 0.05, respectively). There
      was correlation between HRV reduction and a lower level of physical activity in
      daily life, besides worse health-related quality of life, functional status, and
      respiratory and peripheral muscle force. Cardiac autonomic function of patients
      with COPD is not related to disease severity but mainly to the level of physical
      activity in daily life.

PMID- 18815833
TI  - Imprinted noncoding RNAs.
AB  - Imprinted genes are silenced in a parental-specific manner and tend to occur in
      clusters. All well-characterised imprinted clusters contain noncoding RNAs that
      are silenced according to parental origin. These can be broadly classified into
      long noncoding RNAs and short regulatory RNAs. Functional testing has shown that
      long noncoding RNAs can be crucial imprinting elements and act in cis throughout
      the cluster to silence protein-coding genes. Whether silencing occurs via
      transcription of the noncoding RNA or the actual transcript is not clear. The
      short regulatory RNAs, both small nucleolar RNAs and microRNAs, act in trans,
      generally outside the cluster from which they arise. As these RNAs are expressed
      according to parental origin, the regulation of their targets is also parental
      specific. We review knowledge of imprinted noncoding RNAs and models for how they
      function.

PMID- 18815835
TI  - Designing safety into the minimally invasive surgical revolution: a commentary
      based on the Jacques Perissat Lecture of the International Congress of the
      European Association for Endoscopic Surgery.
AB  - Surgical errors with minimally invasive surgery differ from those in open
      surgery. Perforations are typically the result of trocar introduction or
      electrosurgery. Infections include bioburdens, notably enteric viruses, on
      complex instruments. Retained foreign objects are primarily unretrieved device
      fragments and lost gallstones or other specimens. Fires and burns come from
      illuminated ends of fiber-optic cables and from electrosurgery. Pressure ischemia
      is more likely with longer endoscopic surgical procedures. Gas emboli can occur.
      Minimally invasive surgery is more dependent on complex equipment, with high
      likelihood of failures. Standardization, checklists, and problem reporting are
      solutions for minimizing failures. The necessity of electrosurgery makes
      education about best electrosurgical practices important. The recording of
      minimally invasive surgical procedures is an opportunity to debrief in a way that
      improves the reliability of future procedures. Safety depends on reliability,
      designing systems to withstand inevitable human errors. Safe systems are
      characterized by a commitment to safety, formal protocols for communications,
      teamwork, standardization around best practice, and reporting of problems for
      improvement of the system. Teamwork requires shared goals, mental models, and
      situational awareness in order to facilitate mutual monitoring and backup. An
      effective team has a flat hierarchy; team members are empowered to speak up if
      they are concerned about problems. Effective teams plan, rehearse, distribute the
      workload, and debrief. Surgeons doing minimally invasive surgery have a unique
      opportunity to incorporate the principles of safety into the development of their
      discipline.

PMID- 18815836
TI  - Single-incision laparoscopic cholecystectomy: surgery without a visible scar.
AB  - Laparoscopic cholecystectomy has been recognized since 1992 as the gold standard
      procedure for gallbladder surgery. The authors propose a single-incision
      laparoscopic (SILS) cholecystectomy as a step toward less invasive surgical
      procedures. A single intraumbilical 12-mm incision is made, and the umbilicus is
      pulled out, exposing the fascia. Pneumoperitoneum is induced with the Versastep
      Veress access needle. A 5-mm trocar then is introduced, and the abdominal cavity
      is explored with a 5-mm 30 degrees optic. Second and third trocars are introduced
      respectively at the left and right sides, near the first trocar. Two sutures are
      used to suspend the gallbladder and to ensure optimal exposure of the Triangle of
      Calot. Dissection is performed as a normal retrograde cholecystectomy using an
      Endoshear roticulator in the left trocar and an Endograsp roticulator in the
      right hand. The cystic artery and cystic duct are clipped separately with a
      standard 5-mm clip applier and then excised. The gallbladder is removed through
      the umbilical incision. Of the 12 patients who underwent SILS cholecystectomy
      without major complications, 8 had previously undergone other laparoscopic
      surgeries. The body mass index (BMI) exceeded 35 in three cases. Operative time
      decreased and stabilized from the first 3-h SILS cholecystectomy to approximately
      50 min after the first five cases. At this writing, the authors find SILS
      cholecystectomy to be feasible, safe, and effective.

PMID- 18815837
TI  - Endoscopic implantation of polymethylmethacrylate augments the gastroesophageal
      antireflux barrier: a short-term study in a porcine model.
AB  - BACKGROUND AND AIMS: Endoscopic injection of filler agents into the
      esophagogastric junction has been developed to augment the antireflux barrier and
      decrease gastroesophageal reflux (GER). However, evidence of efficacy is lacking
      and serious complications have been reported in humans. The aim of this study was
      to assess whether endoscopic implantation of polymethylmethacrylate augments the
      antireflux barrier in a porcine model for GER. METHODS: Large White pigs
      underwent esophageal manometry, gastric yield pressure (GYP), and gastric yield
      volume (GYV) measurements and implantation of PMMA in the distal esophagus under
      general anesthesia. After follow-up of 28 days, esophageal manometry and gastric
      yield measurements were repeated and animals sacrificed. RESULTS: Implantation of
      PMMA was performed in 18 animals, and 14 animals survived 28 days. There was a
      significant increase in GYP (10.7 mmHg versus 8.1 mmHg; p = 0.017) and GYV (997
      ml versus 393 ml; p < 0.001) after PMMA implantation, whereas resting LES
      pressure did not change significantly. Acute inflammatory changes and fibrous
      tissue deposits were found surrounding the PMMA implants during histology. One
      animal died after esophageal perforation and three others due to pneumonia (two)
      and colon perforation (one) in the postoperative period. CONCLUSIONS: Endoscopic
      implantation of PMMA in the distal esophagus augments the antireflux barrier 28
      days after the procedure. However, esophageal perforation points to the need for
      technical refinements to make the procedure safer.

PMID- 18815838
TI  - Ergonomic risk associated with assisting in minimally invasive surgery.
AB  - BACKGROUND: Given the physical risks associated with performing laparoscopic
      surgery, ergonomics to date has focused on the primary minimally invasive
      surgeon. Similar studies have not extended to other operating room staff.
      Simulation of the assistant's role as camera holder and retractor during a Nissen
      fundoplication allowed investigation of the ergonomic risks involved in these
      tasks. METHODS: Seven subjects performed camera navigation and retraction tasks
      using a box trainer on an operating room table that simulated an adult patient in
      low lithotomy position. Each subject stood on force plates at the simulated
      patient's left side. A laparoscope was introduced through a port into the
      training box with four 2-cm circles as rear-panel targets located in relation to
      the assistant as distal superior, proximal superior, distal inferior, and
      proximal inferior target effects. The subjects held the camera with their left
      hand, pointing it at a target. The task was to match the target to a circle
      overlaid on the monitor. Simultaneously, a grasper in the right hand grasped and
      pulled a panel-attached band. A minute signal moved the subject to the next
      target. Each trial had three four-target repetitions (phase effect). The subjects
      performed two separate trials: one while holding the camera from the top and one
      while holding it from the bottom (grip effect). A 4 x 3 x 2 (target x phase x
      grip) repeated-measures design provided statistics. Dividing the left force-plate
      vertical ground reaction forces (VGRF) by the total VGRF from both plates
      provided a weight-loading ratio (WLR). RESULTS: The WLR significantly increased
      (p < 0.005) with proximal targets (2 by 80% and 4 by 79%). The WLR decreased 75%,
      74%, and 71% over time. No difference existed between the grip strategies (grip
      effect, p > 0.5). CONCLUSIONS: A high-risk ergonomic situation is created by the
      assistant's left or caudal leg disproportionately bearing 70-80% of body weight
      over time. A distance increase between the camera head location and the camera
      holder increases ergonomic risk. The phase effect was interpreted as a
      compensatory rebalancing to reduce ergonomic risk. Ergonomic solutions minimizing
      ergonomic risks associated with laparoscopic assistance should be considered.

PMID- 18815840
TI  - Exudation of alcohol and aldehyde sugars from roots of defoliated Lolium perenne
      L. grown under sterile conditions.
AB  - Root exudates were collected over a 27 day period from defoliated and non
      defoliated Lolium perenne L. plants grown under sterile conditions in
      microlysimeters. Eleven individual sugars, including both aldehyde and alcohol
      sugars, were identified and quantified with a gas chromatograph-mass spectrometer
      (GC-MS). There was no change in the number of sugars present between 7 and 27
      days, but the exudation of alcohol sugars decreased rapidly at about day 12.
      Xylose and glucose were present in the largest amounts. Defoliation initially
      increased the total amount of sugars in the exudates, but continuous defoliation
      reduced total sugar exudation by 16% and induced changes in the exudation
      patterns of individual sugars. Defoliation enhanced exudation of erythritol,
      threitol, and xylitol, reduced exudation of glucose and arabitol, but had little
      effect on the amounts of other sugars exuded. The more complex 6 C, 5 OH aldehyde
      sugars, especially glucose, showed changes earlier and to a greater extent (17
      days), than the 5 C, 4 OH (xylose and ribose) and 6 C 4 OH (fucose) aldehyde
      groups. These findings confirm the general finding that repeated defoliation
      reduces the quantity of total sugars exuded, but the pattern of release of
      individual sugars is complex and variable.

PMID- 18815839
TI  - Functional annotation and analysis of expressed sequence tags from the
      hepatopancreas of mitten crab (Eriocheir sinensis).
AB  - Due to its popularity as a traditional food, intensive harvesting of the mitten
      crab (Eriocheir sinensis) is common and has lead to an increase in disease
      incidence, resulting in catastrophic losses to crab aquaculture. The
      hepatopancreas of E. sinensis is not only an important digestive organ but also
      an indispensable immune organ. We constructed a nonnormalized cDNA library from
      the hepatopancreas of E. sinensis and acquired 3,297 high-quality expressed
      sequence tags representing 1,178 unigenes. More than half of these unigenes were
      novel genes for this species; the remaining had homologs in public databases,
      which is of great importance for future functional research. We also investigated
      the association of these genes with immune processes for insight into one of the
      main functions of the hepatopancreas besides metabolism. Despite the relatively
      low sampling scalar of our cDNA library, we were able to demonstrate several
      important properties of the hepatopancreatic transcriptome and identified
      numerous genes that were closely associated with immune responses. These results
      might serve as the basis for an in-depth genomics study of E. sinensis, including
      transcriptome analysis, physical mapping, and whole genome sequencing.

PMID- 18815841
TI  - Lymphovascular invasion and lobular histology are associated with increased
      incidence of isolated tumor cells in sentinel lymph nodes from early-stage breast
      cancer patients.
AB  - BACKGROUND: Isolated tumor cells (ITC) are more likely to be identified when
      serial sectioning and immunohistochemical staining are used to evaluate sentinel
      lymph nodes (SLN). Our goal was to identify clinicopathologic features associated
      with ITC in patients undergoing sentinel lymph node dissection (SLND). METHODS:
      We reviewed clinicopathologic data for 3557 patients with no clinical evidence of
      lymph node metastases undergoing SLND between November 1993 and March 2007.
      Patients were staged according to the 6th edition of the American Joint Committee
      on Cancer staging system, with metastasis <or=.2 mm classified as ITC. RESULTS: A
      SLN was identified in 3475 patients (97.7%), including 2518 (72.4%) with negative
      nodes and 169 (4.9%) with ITC. A statistically significant association existed
      between lobular histology and the identification of ITC; 13.6% of patients with
      ITC had lobular histology versus 7.3% of patients with a negative SLN (P = .003).
      The presence of lymphovascular invasion (LVI) was also associated with ITC; 18.3%
      of patients with ITC had LVI in the primary tumor versus 8.5% of patients with a
      negative SLN (P < .001). No difference existed between patients with and without
      ITC with respect to T stage, grade, estrogen receptor, progesterone receptor,
      HER2/neu status, or biopsy method. CONCLUSION: The association between ITC and
      LVI, a known predictor of poor outcome, suggests ITC may have clinical relevance.
      The relationship between lobular histology and ITC is consistent with the known
      pattern of lobular metastases, which frequently present as small foci requiring
      immunohistochemistry for detection. Longer follow-up is needed to determine
      whether ITC have prognostic significance.

PMID- 18815842
TI  - Optimizing detection of major depression among patients with coronary artery
      disease using the patient health questionnaire: data from the heart and soul
      study.
AB  - BACKGROUND: Clinical guidelines recommend depression screening in patients with
      coronary artery disease (CAD), but how to accomplish this is unclear. OBJECTIVE:
      We evaluated the test characteristics of the two-item Patient Health
      Questionnaire (PHQ-2), the nine-item Patient Health Questionnaire (PHQ-9), and a
      two-step screening approach (PHQ-2 then PHQ-9 if positive on PHQ-2), compared
      with the Computerized Diagnostic Interview Schedule (C-DIS) for major depression.
      We also evaluated a "PHQ diagnosis" of depression, requiring five of nine
      symptoms "more than half the days," compared with the C-DIS. DESIGN: Cross
      sectional study of 1,024 outpatients with CAD. MAIN RESULTS: Two hundred twenty
      four patients (22%) had current major depression. Optimal cutpoints were >or=2
      for the PHQ-2 (82% sensitive, 79% specific) and >or=6 for the PHQ-9 (83%
      sensitive, 76% specific). The two-step screening approach was less sensitive
      (75%), but more specific (84%), than the PHQ-2 or PHQ-9 alone. The "PHQ
      diagnosis" had low sensitivity (28%), but high specificity (96%). CONCLUSIONS:
      Cutpoints of >or=2 on the PHQ-2 and >or=6 on the PHQ-9 had similar test
      characteristics. A two-step approach using the PHQ-2 followed by the PHQ-9 was no
      better than either instrument alone. A "PHQ diagnosis" of depression had high
      specificity, but poor sensitivity.

PMID- 18815843
TI  - A randomized controlled trial of team-based care: impact of physician-pharmacist
      collaboration on uncontrolled hypertension.
AB  - OBJECTIVE: Evaluate the effectiveness of collaborative management of hypertension
      by primary care-pharmacist teams in community-based clinics. STUDY DESIGN: A 12
      month prospective, single-blind, randomized, controlled trial in the Providence
      Primary Care Research Network of patients with hypertension and uncontrolled
      blood pressure. METHODS: As compared to usual primary care, intervention
      consisted of pharmacy practitioners participating in the active management of
      hypertension in the primary care office according to established collaborative
      treatment protocols. At baseline, there was no significant difference in blood
      pressure between groups. Primary outcome measures were the differences in mean
      systolic and diastolic blood pressures between arms at study end. Secondary
      measures included blood pressure goal attainment (<140/90 mmHg), hypertension
      related knowledge, medication adherence, home blood pressure monitoring, resource
      utilization, quality of life, and satisfaction. RESULTS: A total of 463 subjects
      were enrolled (n = 233 control, n = 230 intervention). Subjects receiving the
      intervention achieved significantly lower systolic (p = 0.007) and diastolic (p =
      0.002) blood pressures compared to control (137/75 mmHg vs. 143/78 mmHg). In
      addition, 62% of intervention subjects achieved target blood pressure compared to
      44% of control subjects (p = 0.003). The intervention group received more total
      office visits (7.2 vs. 4.9, p < 0.0001), however had fewer physician visits (3.2
      vs. 4.7, p < 0.0001) compared to control. Intervention subjects were prescribed
      more antihypertensive medications (2.7 vs. 2.4, p = 0.02), but did not take more
      antihypertensive pills per day (2.4 vs. 2.5, p = 0.87). There were minimal
      differences between groups in hypertension-related knowledge, medication
      adherence, quality of life, or satisfaction. CONCLUSIONS: Patients randomized to
      collaborative primary care-pharmacist hypertension management achieved
      significantly better blood pressure control compared to usual care with no
      difference in quality of life or satisfaction.

PMID- 18815844
TI  - Pancreatic adenocarcinoma in the pregnant patient: a case report and literature
      review.
AB  - Pancreatic cancer is the fifth most common cause of cancer-related death in the
      USA. However, the antepartum diagnosis of pancreatic adenocarcinoma in the
      pregnant patient is exceedingly rare, with only six cases previously reported in
      the literature. Optimizing both maternal and fetal health outcomes is
      particularly challenging when surgical procedures are necessary for staging
      and/or therapeutic purposes--as these interventions often pose significant risks
      to both the mother and the developing fetus. In this article, we report a case of
      pancreatic adenocarcinoma diagnosed during pregnancy and review the literature on
      the management issues confronted in this unique clinical situation.

PMID- 18815846
TI  - Farewell.

PMID- 18815845
TI  - Recombinant collagen for animal product-free dextran microcarriers.
AB  - Manufacturers of vaccines and other biologicals are under increasing pressure
      from regulatory agencies to develop production methods that are completely animal
      component-free. In order to comply with this demand, alternative cell culture
      substrates to those now on the market, primarily collagen or gelatin, must be
      found. In this paper, we have tested a number of possible substitutes including
      recombinant collagen, a 100-kDa recombinant gelatin fragment and a peptide
      derived from a cell-binding region of type I collagen. The small 15-amino acid
      peptide did not support attachment of human fibroblasts in monolayer culture. The
      100-kDa gelatin fragment supported cell attachment in monolayer culture, but was
      significantly less active than intact porcine gelatin. Recombinant type I
      collagen was as successful in promoting cell attachment as native collagen, and
      both were more effective than porcine gelatin. Based on these data, dextran
      microspheres were treated with the same attachment proteins--porcine gelatin,
      native collagen, or recombinant collagen. The same trends were observed as in
      monolayer culture. Concentrations of the recombinant collagen (as well as native
      collagen) supported cell attachment on dextran microspheres at concentrations as
      low as 0.01 microg/cm(2). Treatment of the dextran with a low level of
      polyethylenimine, a cationic moiety, further enhanced attachment when used in
      conjunction with the low concentration of recombinant collagen. Where there was
      increased cell attachment, increased proliferation followed. We are confident,
      based on these findings, that a fully recombinant substitute could replace
      gelatin in current microcarrier preparations without losing the cell growth
      benefits provided by the native protein.

PMID- 18815847
TI  - Laparoscopically assisted ERCP in a case of acute cholangitis in a patient with
      biliopancreatic diversion with distal gastric preservation.
AB  - Roux-en-Y gastric bypass, biliopancreatic diversion (BPD; Scopinaro's technique),
      and BPD with distal gastric preservation (BPDGP) are different surgical
      procedures, currently performed with laparoscopic assistance, successfully used
      as a treatment for morbid obesity. All of these modalities bear the burden of a
      difficult access when it comes to explore and work within the biliary tract. We
      present a case of acute cholangitis due to choledocholithiasis in a patient with
      BPDGP for morbid obesity successfully managed by laparoscopy-assisted endoscopic
      retrograde cholangiopancreatography through the gastric remnant.

PMID- 18815848
TI  - Morbid obesity and subsequent pancreatic cancer: pylorus-preserving
      pancreatoduodenectomy after laparoscopic sleeve gastrectomy.
AB  - Morbid obesity is a recognized risk factor for gastrointestinal cancer. Little is
      known about pancreatic cancer developing after gastric bypass surgery or about
      surgery for this type of tumor following bariatric surgery. This report describes
      a case of pancreatic head cancer identified 3 months after laparoscopic sleeve
      gastrectomy for morbid obesity. During routine follow-up, mild abdominal pain and
      elevated pancreatic enzymes prompted computed tomography, which revealed mild
      edematous pancreatitis. Hyperbilirubinemia developed, and magnetic resonance
      imaging showed a pancreatic head tumor. CA19-9 was elevated. After a pylorus
      preserving pancreatic head resection, the postoperative course was uneventful.
      The patient received adjuvant chemotherapy. Unfortunately, at the time of writing
      (9 months postoperatively), a local recurrence and hepatic metastases were
      diagnosed. Patients treated with bariatric surgery who develop new symptoms or
      report constant mild symptoms should be evaluated using endoscopy and
      radiomorphological imaging. Interdisciplinary obesity treatment can then offer
      significant benefits for the patient, particularly in the case of pancreatic
      cancer, which is still difficult to diagnose. In addition, there is a need for
      epidemiological studies of patients who undergo bariatric surgery and
      subsequently develop cancer.

PMID- 18815849
TI  - GLP-1 and adiponectin: effect of weight loss after dietary restriction and
      gastric bypass in morbidly obese patients with normal and abnormal glucose
      metabolism.
AB  - BACKGROUND: It has been proposed that there is improvement in glucose and insulin
      metabolism after weight loss in patients who underwent diet restriction and
      bariatric surgery. METHODS: Eleven normal glucose tolerant (NGT) morbidly obese
      patients [body mass index (BMI), 46.1+/-2.27 g/m2] and eight abnormal glucose
      metabolism (AGM) obese patients (BMI, 51.20 kg/m2) were submitted to diet
      restriction and bariatric surgery. Prospective study on weight loss changes, over
      the glucose, insulin metabolism, glucagon-like peptide-1 (GLP-1), and adiponectin
      levels were evaluated by oral glucose tolerance test during three periods: T1
      (first evaluation), T2 (pre-surgery), and T3 (9 months after surgery). RESULTS:
      Insulin levels improved after surgery. T1 was 131.1+/-17.60 pmol/l in the NGT
      group and 197.57+/-57.94 pmol/l in the AGM group, and T3 was 72.48+/-3.67 pmol/l
      in the NGT group and 61.2+/-9.33 pmol/l in the AGM group. The major reduction was
      at the first hour of the glucose load as well as fasting levels. At 9 months
      after surgery (T3), GLP-1 levels at 30 and 60 min had significantly increased in
      both groups. It was observed that the AGM group had higher levels of GLP-1 at 30
      min (34.06+/-6.18 pmol/l) when compared to the NGT group (22.69+/-4.04 pmol/l).
      Homeostasis model assessment of insulin resistance from the NGT and AGM groups
      had a significant reduction at periods T3 in relation to T1 and T2. Adiponectin
      levels had increased concentration in both groups before and after surgical
      weight loss. However, it did not have any statistical difference between periods
      T1 vs. T2. CONCLUSIONS: Weight loss by surgery leads to improvement in the
      metabolism of carbohydrates in relation to sensitivity to the insulin,
      contributing to the reduction of type 2 diabetes incidence. This improvement also
      was expressed by the improvement of the levels of adiponectin and GLP-1.

PMID- 18815850
TI  - Computer navigation-assisted versus minimally invasive TKA: benefits and
      drawbacks.
AB  - Computer-navigated and minimally invasive TKAs are emerging technologies that
      have distinct strengths and weaknesses. We compared duration of surgery, length
      of hospitalization, Knee Society scores, radiographic alignments, and
      complications in two unselected groups of 81 consecutive knees that underwent TKA
      using either a minimally invasive approach or computer navigation. The two groups
      were operated on by two different surgeons over differing timeframes. The mean
      surgical time was longer in the navigated group by 63 minutes. The Knee Society
      scores and lengths of hospitalization of the two groups were similar. The
      postoperative component alignments of the two groups were similar; the mean
      femoral valgus and tibial varus angles of the navigation group changed from 96
      degrees and 88 degrees preoperatively to 95 degrees and 89 degrees
      postoperatively, respectively, and in the minimally invasive group, the mean
      femoral valgus angles and tibial varus angles changed from 97 degrees and 88
      degrees preoperatively to 95 degrees and 89 degrees postoperatively,
      respectively. There were 11 major and three minor complications in the navigation
      group, including one revision, two femoral shaft fractures, four reoperations for
      knee stiffness, and four instances of bleeding from tracker sites. We believe the
      higher incidence of complications in addition to the longer operative time in the
      navigated group may outweigh any potential radiographic benefits. LEVEL OF
      EVIDENCE: Level II, therapeutic study. See the Guidelines for Authors for a
      complete description of levels of evidence.

PMID- 18815851
TI  - The Hospital for the Ruptured and Crippled Eugene H. Pool, fourth Surgeon-in
      Chief 1933-1935 followed by Philip D. Wilson, fifth Surgeon-in-Chief 1935.
AB  - In 1933, for the second time in the history of the Hospital for the Ruptured and
      Crippled (R & C), a general surgeon, Eugene Hillhouse Pool, MD, was appointed
      Surgeon-in-Chief by the Board of Managers of the New York Society for the Relief
      of the Ruptured and Crippled. R & C (whose name was changed to the Hospital for
      Special Surgery in 1940), then the oldest orthopaedic hospital in the country,
      was losing ground as the leading orthopaedic center in the nation. The R & C
      Board charged Dr. Pool with the task of recruiting the nation's best orthopaedic
      surgeon to become the next Surgeon-in-Chief. Phillip D. Wilson, MD, from the
      Massachusetts General Hospital in Boston and the Harvard Medical School was
      selected and agreed to accept this challenge. He joined the staff of the Hospital
      for the Ruptured and Crippled in the spring of 1934 as Director of Surgery and
      replaced Dr. Pool as Surgeon-in-Chief the next year. It was the time of the Great
      Depression, which added a heavy financial toll to the daily operations of the
      hospital. With a clear and courageous vision, Dr. Wilson reorganized the
      hospital, its staff responsibilities, professional education and care of
      patients. He established orthopaedic fellowships to support young orthopaedic
      surgeons interested in conducting research and assisted them with the initiation
      of their new practices. Recognizing that the treatment of crippling conditions
      and hernia were becoming separate specialties, one of his first decisions was to
      restructure the Hernia Department to become the General Surgery Department. His
      World War I experiences in Europe helped develop his expertise in the fields of
      fractures, war trauma and amputations, providing a broad foundation in
      musculoskeletal diseases that was to be beneficial to him in his future role as
      the leader of R & C.

PMID- 18815852
TI  - Similar wear in total hip arthroplasties with metallic or zirconia femoral heads.
AB  - Ceramic femoral heads have been used in an attempt at reducing polyethylene wear
      of total hip arthroplasties. Clinical results with zirconia femoral heads have
      been mixed. This study was undertaken to compare the polyethylene wear and
      incidence of periprosthetic osteolysis in total hip replacements performed using
      a 28-mm zirconia versus a 28-mm cobalt chromium femoral head. Thirty-five hips
      with a 28-mm cobalt chromium head and 68 hips with a 28-mm zirconia head were
      evaluated after a minimum follow-up of 2 years (average, 4.0 years; range, 2.0 to
      9.1 years). A monoblock acetabular component was used in all patients.
      Polyethylene wear was measured in serial radiographs from 58 of the hips
      utilizing a computer-assisted vector wear technique. Periacetabular osteolysis
      developed in three patients (two with a zirconia head and one with a cobalt
      chromium head). The total wear and the annual wear rate were 0.48 mm and 0.11
      mm/year for the cobalt chromium heads and 0.53 mm and 0.14 mm/year for the
      zirconia heads, respectively. We found no benefit with respect to the rate of
      polyethylene wear or incidence of osteolysis with the use of zirconia femoral
      heads.

PMID- 18815853
TI  - The Kathryn O. and Alan C. Greenberg Center for Skeletal Dysplasias: an
      interdisciplinary approach.
AB  - Skeletal dysplasias are a group of over 300 genetic conditions often marked by
      short stature and a range of orthopedic problems. To meet the diverse medical,
      orthopedic, and psychosocial needs of individuals with skeletal dysplasias, the
      Kathryn O. and Alan C. Greenberg Center for Skeletal Dysplasias was organized at
      Hospital for Special Surgery in 2003. The center is the only one of its kind in
      the New York City metropolitan area and is dedicated to providing comprehensive
      medical care for individuals with skeletal dysplasias. The center is staffed by
      an interdisciplinary core team of health professionals consisting of an
      orthopedic surgeon, a medical geneticist, a genetic counselor/clinical
      coordinator, and a social worker. This interdisciplinary team of health
      professionals is committed to improving the quality of life for people with
      skeletal dysplasias through clinical care, research, education, and patient
      advocacy. Goals are achieved through a collaborative process that utilizes the
      expertise of the different professionals.

PMID- 18815854
TI  - One- versus two-incision technique for distal biceps tendon repair.
AB  - There are several techniques that have been described for distal biceps tendon
      repair but there is still controversy regarding the optimal technique. Our
      hypothesis is that the single-incision technique will have a similar complication
      rate and functionally equivalent restoration of function compared with the two
      incision approach. A retrospective review of consecutive biceps tendon repairs
      was performed at one institution over a 5-year period. Thirty-six patients met
      the inclusion criteria and 26 were available for follow-up including subjective
      assessment, physical examination, and strength testing. Patients were divided
      into two groups based on the surgical approach utilized: 12 patients underwent
      single-incision repair and 14 had a two-incision repair. The average follow-up
      was 33 months (minimum 13; maximum 75). There were no statistically significant
      differences in regards to flexion strength or endurance, supination strength or
      endurance, or complication rates between the two techniques. In conclusion, both
      surgical techniques led to adequate restoration of strength with a low
      complication rate. Both techniques are safe to perform and should be guided by
      surgeon comfort with the approach.

PMID- 18815855
TI  - Case report of spontaneous, nonspinal fractures in a multiple myeloma patient on
      long-term pamidronate and zoledronic acid.
AB  - Pamidronate and zoledronic acid are two potent intravenous bisphosphonates used
      in the treatment of multiple myeloma as well as osteoporosis. While the concern
      for heightened fracture risk in a patient on long-term bisphosphonate treatment
      for malignancy has been previously noted, we present the first case of
      spontaneous, nonspinal fractures in a patient undergoing treatment for multiple
      myeloma. The patient had a positive 9-year history of bisphosphonate treatment
      and presented with sequential subtrochanteric stress fractures of the left and
      right femurs. Pathological reports of fracture site biopsies demonstrate signs
      consistent with ametabolic bone and no malignancy. These findings point to
      extreme inhibition of bone turnover by bisphosphonates as the cause of this
      patient's morbidity. This is a single retrospective case study (level IV
      evidence).

PMID- 18815856
TI  - A review of the treatment of pelvic discontinuity.
AB  - Pelvic discontinuity is a complex entity with a high surgical complication rate
      and no standardized treatment to date. Revision hip arthroplasty in cases of
      massive bone loss remains a difficult and unsolved problem. The goal of the
      surgeon is to preserve limb function by restoring bone stock and the biomechanics
      of the hip. In cases of severe acetabular bone loss, biologic fixation is often
      inadequate, requiring extensive bone grafting and reconstructive cages.
      Reconstructive cages are the most commonly used devices and are designed to
      bridge bone defects, protect the bone graft, and reestablish the rotation center
      of the hip. A major limitation of current cages is that they do not allow for
      biologic fixation. We review the options for treating patients with massive bone
      loss and pelvic discontinuity and discuss therapeutic options and the clinical
      and radiological criteria for success.

PMID- 18815857
TI  - Volar dislocation of the fourth and fifth carpometacarpal joints: a case report
      and review of the literature.
AB  - We report the treatment of a volar dislocation to the fourth and fifth
      carpometacarpal (CMC) joints. Plain radiographs were used to evaluate this
      unusual injury before surgery. Open reduction and internal fixation using K-wires
      restored the normal anatomic relationships of the CMC joints. This very rare
      injury is often difficult to recognize. A careful neurologic assessment of the
      patient is a necessity, as well as obtaining proper radiographs of the hand. A
      review of the literature is presented.

PMID- 18815858
TI  - Vitamin D deficiency: a common occurrence in both high-and low-energy fractures.
AB  - As a consequence of newly elevated standards for normal vitamin D levels, there
      is a renewed interest in vitamin D insufficiency and deficiency (<32 and <20
      ng/ml, respectively) in the orthopedic patient population. This study tests the
      hypothesis that vitamin D insufficiency is comparably prevalent among both high-
      and low-energy fracture patients. A retrospective analysis of the medical records
      for 44 orthopedic trauma in-patients with non-vertebral fractures was conducted
      from June 1, 2006 to February 1, 2007. The obtained data included a 25
      hydroxyvitamin D level, age, gender, and reason for admission; high-energy vs.
      low-energy fracture. Vitamin D insufficiency, 25(OH)D <32 ng/ml, was found in
      59.1% of the patients. Significantly, more women (75%) than men (40%) were
      vitamin D insufficient among all fracture patients and specifically among high
      energy fractures, 80% women insufficient vs. 25% men insufficient. In women, both
      high- and low-energy fractures present with vitamin D insufficiency (80% of high
      energy fractures and 71.4% of low-energy fractures). In men, the mean vitamin D
      level was lower for low-energy fractures (16 ng/ml) compared to high-energy
      fractures (32 ng/ml). In addition, men with low-energy fractures were
      significantly older than men with high-energy fractures and women with low-energy
      fractures were also older. Statistically, more vitamin D insufficiency is seen in
      women and our results are consistent with the gender difference seen in the
      general population. Even among younger men who sustain a high-energy fracture,
      25% are vitamin D insufficient. Women with fractures regardless of age or
      fracture energy level have low vitamin D levels. Levels of 25(OH)D should be
      measured in all orthopedic trauma patients and the American Society for Bone and
      Mineral Research and National Osteoporosis Foundation currently recommend that
      vitamin D levels should be corrected.

PMID- 18815859
TI  - Ultrasound-guided ganglion cyst aspiration.

PMID- 18815860
TI  - Magnetic resonance imaging of adhesive capsulitis: correlation with clinical
      staging.
AB  - The purpose of this study was to evaluate non-contrast magnetic resonance imaging
      (MRI) findings of adhesive capsulitis and correlate them with clinical stages of
      adhesive capsulitis. This will hopefully define a role for shoulder MR imaging in
      the diagnosis of adhesive capsulitis as well as in potentially directing
      appropriate treatment. Forty-seven consecutive non-contrast magnetic resonance
      imaging examinations of 46 patients with a clinical diagnosis of adhesive
      capsulitis were retrospectively reviewed and correlated with clinical staging.
      Specific MRI criteria correlated with the clinical stage of adhesive capsulitis,
      including the thickness and signal intensity of the joint capsule and synovium as
      well as the presence and severity of scarring in the rotator interval. Routine
      MRI of the shoulder without intraarticular administration of gadolinium can be
      used to diagnose all stages of adhesive capsulitis, including stage 1, where
      findings may be subtle on clinical examination. We believe that future studies
      assessing the role of MRI in guiding the initiation of appropriate treatment
      should be undertaken.

PMID- 18815861
TI  - Von Willebrand factor, red cell fragmentation, and disease activity in systemic
      lupus erythematosus.
AB  - This study sought to determine whether the plasma levels of Von Willebrand factor
      (vWf) and the degree of red blood cell (RBC) fragmentation on peripheral smear
      correlate with disease activity in systemic lupus erythematosus (SLE). Forty
      consecutive patients who fulfilled the criteria for SLE were studied
      prospectively for 1 year. Patients were categorized according to the SLE Disease
      Activity Index (SLEDAI) as either active (>2) or inactive disease and followed up
      monthly (active) or quarterly (inactive). At each visit, patients were examined
      fully and had complete blood count, tests on antibodies to double-stranded DNA,
      C3, and C4 levels, and urinalysis. Citrated plasma was analyzed for vWf antigen
      by standard enzyme-linked immunosorbent assay. A Wright's stained blood smear was
      obtained and schistocytes were quantitated on blood smear. The number of
      schistocytes per 500 RBCs was determined and a schistocyte index (SI) was
      calculated. At baseline, vWf correlated with SLEDAI (r = 0.64, p < 0.01), SI
      correlated with SLEDAI (r = 0.62, p < 0.01), and vWf and SI correlated with each
      other (r = 0.41, p = 0.01). There was an inverse correlation between baseline C3
      levels and vWf (r = 0.49, p = 0.0013) and C3 levels and SI (r = 0.40, p = 0.01).
      Over time, there was also a correlation of SLEDAI with vWf (r = 0.53, p = 0.002)
      and SI (r = 0.57;p = 0.002). The relation of vWf with SI approached but did not
      reach statistical significance (r = 0.37, p = 0.06). We found that the plasma
      levels of vWf and the degree of RBC fragmentation correlate with lupus disease
      activity over time. Therefore, inflammation in SLE may be associated with
      endothelial injury.

PMID- 18815862
TI  - Facioscapulohumeral dystrophy: case report and discussion.
AB  - Facioscapulohumeral dystrophy (FSHD) is often cited as the third most common form
      of muscular dystrophy. Therefore, it should be considered in patients with
      complaints of progressive weakness. We present the case of a man with facial,
      truncal, and leg weakness that initially sought medical attention for lower back
      pain. Electrodiagnostic testing revealed findings in the trapezius, serratus
      anterior, biceps, triceps, pectoralis major, tibialis anterior, and gastrocnemius
      muscles consistent with a myopathic disorder. Subsequent genetic testing
      identified a FSHD allele size consistent with a FSHD deletion mutation.
      Therefore, confirming the diagnosis of FSHD. Unfortunately, no effective
      treatments currently exist for FSHD. However, supportive measures involving
      physical therapy and the use of orthotics may aid in improving function and
      mobility.

PMID- 18815863
TI  - Lumbar zygapophysial joint radiofrequency denervation: a long-term clinical
      outcome study.
AB  - Zygapophysial joint (z-joint) pain has long been suggested to be one of the
      sources of low back pain. Radiofrequency denervation of the medial branches of
      the dorsal rami to treat z-joint pain is an outpatient minimally invasive
      treatment option. There have been many short-term studies to determine the
      outcome of the procedure, but few long-term studies have been conducted. Our goal
      is to clarify whether radiofrequency denervation has any long-term clinical
      benefit. In this retrospective cohort study, a total of 42 patients (25 women and
      17 men), with an average follow-up of 3.5 years, with clinical signs of
      zygapophysial joint involvement who had failed conservative treatment (pre
      procedure symptom duration mean 6.03 years; range 5 months to 48 years) and had a
      favorable response to a diagnostic medial branch block or zygapophysial joint
      injection, were identified. The identified subjects underwent radiofrequency
      denervation at the Hospital for Special Surgery Physiatry Department from 1998 to
      2006. Patient's records were reviewed, and a questionnaire was provided,
      completed on phone call follow-up, or mailed by the patient. The success of this
      intervention in providing improvement in pain and function was analyzed using the
      Numerical Rating Scale (NRS)-11, North American Spine Society (NASS) four-point
      satisfaction index, and a modified Roland-Morris Disability Questionnaire (RMDQ).
      Fifty-two percent of patients reported a successful outcome with improved
      function at a minimum follow-up period of 2 years (mean 3.5 years, range 2-8.8
      years). Patients in the failure group were more likely to be older and have
      moderate to severe neuroforaminal stenosis (77.8%) compared to patients in the
      success group (24.2%). Radiofrequency denervation in selected patients with
      chronic zygapophysial joint-mediated low back pain provides long-term reduction
      in pain and improved function with minimum morbidity.

PMID- 18815866
TI  - Rapid genotyping of tumor necrosis factor alpha with fluorogenic hybridization
      probes on the LightCycler.
AB  - Genotyping of tumor necrosis factor alpha (TNF-alpha) has become an important
      procedure in the selection of high-risk population of septic shock and prevention
      from death due to septic shock. We present a single-tube method for TNF-alpha
      genotyping that performed on the LightCycler by melting curve analysis with
      allele-specific fluorescent probe. A fragment covering the polymorphic site is
      amplified in the presence of two fluorescently labeled hybridization probes.
      During amplification, probe hybridization is observed as fluorescence increases
      every cycle as the product accumulates during amplification. A single base
      mismatch resulted in a melting temperature (Tm) shift of 7-8 degrees C, allowing
      for the easy distinction of a common type allele from the polymorphic allele.
      Using this method, genotyping of 104 samples was completed within 1 h without the
      need for any post-PCR sample manipulation, thereby eliminating the risks of end
      product contamination and sample tracking errors. The genotypes determined with
      the LightCycler were identical when compared with a conventional sequencing. The
      simplicity, speed, and accuracy of real-time PCR analysis using FRET probes make
      it the method of choice in the clinical laboratory for genotyping of a variety of
      human DNA polymorphisms and mutations.

PMID- 18815867
TI  - Induction of multidrug resistance proteins in lymphocytes from patients with
      arthritic disorders.

PMID- 18815868
TI  - Serovar-specific immune responses to peptides of variable regions of Chlamydia
      trachomatis major outer membrane protein in serovar D-infected women.
AB  - The role of major outer membrane protein (MOMP) variable regions in the
      interaction of chlamydiae and host cells has been evaluated and their role in
      neutralization of antibodies has been clearly demonstrated. There are also
      studies that delineate the contribution of these regions to the cell-mediated
      immune response of the host and suggest that serovar E elicits serovar-specific
      immune responses in infected humans. However, further studies with other serovars
      are required to confirm these findings and to elucidate the role and importance
      of serovar-specific responses of variable regions of MOMP in other serovars. We,
      therefore, performed a detailed analysis of the humoral and cellular immune
      responses against the serovar D-specific variable segments (VS) of MOMP in women
      infected with Chlamydia trachomatis. We found that VS4 elicits significantly
      higher responses (both humoral and cellular) than other VS peptides (VS1, VS2 and
      VS3). VS4 elicited significantly higher (P < 0.0001) proliferative responses,
      interferon-gamma levels (P < 0.0001) as well as higher prevalence (P < 0.0001) of
      IgG antibodies against VS4 in serovar D-infected patients as compared to patients
      infected with other serovars, suggesting its role in serovar-specific immune
      responses.

PMID- 18815869
TI  - Polymorphisms of methylenetetrahydrofolate reductase and methionine synthase
      genes and bladder cancer risk: a case-control study with meta-analysis.
AB  - Folate deficiency due to the methylenetetrahydrofolate reductase (MTHFR) and
      methionine synthase (MS) variants leads to carcinogenesis by affecting DNA
      synthesis, repair, and methylation. We hypothesized that the MTHFR C677T, A1298C,
      and MS A2756G polymorphisms are associated with risk of bladder cancer. In a case
      control study of 239 bladder cancer cases and 250 cancer-free controls, we found
      that the MTHFR 677TT genotype was statistically significantly associated with an
      increased risk of bladder cancer compared with the 677CC genotype (OR = 2.06, 95%
      CI = 1.16-3.64). Furthermore, the TA haplotype was associated with a
      significantly increased bladder cancer risk (OR = 1.38, 95% CI = 1.05-1.81) than
      was the most common haplotype, CA (e.g., CA denotes MTHFR 677C -1298A). We also
      found that the combined genotypes with 4-6 variant (risk) alleles (i.e., MTHFR
      677T, 1298A, and MS 2756G alleles) were associated with an increased risk of
      bladder cancer (OR = 1.62, 95% CI = 1.03-2.53) compared with those with 0-3
      variants, and this increased risk was more pronounced among subgroup of older
      people (OR = 1.71, 95% CI = 1.03-2.83). A meta-analysis of seven studies did not
      show a significant risk of bladder cancer in the MTHFR polymorphisms. The MTHFR
      polymorphisms and their haplotypes appear to jointly contribute to risk of
      bladder cancer.

PMID- 18815870
TI  - Administration of pigment epithelium-derived factor prolongs bleeding time by
      suppressing plasminogen activator inhibitor-1 activity and platelet aggregation
      in rats.
AB  - We have recently found that pigment epithelium-derived factor (PEDF), a
      glycoprotein with potent neuronal differentiating activity, not only inhibits
      endothelial cell damage, smooth muscle cell proliferation and platelet
      aggregation in vitro, but also suppresses occlusive thrombus formation in rats.
      These observations suggest PEDF may play a protective role against
      atherothrombosis. However, effects of PEDF on hemostasis, fibrinolysis and
      platelet function in vivo are not fully understood. In this study, we examined
      the effects of PEDF on tail vein bleeding time, plasminogen activator inhibitor-1
      (PAI-1) activity and ex vivo-platelet aggregation in rats. Intravenous injection
      of 30 microg PEDF significantly prolonged the tail vein bleeding time by about
      25%. Administration of 30 microg PEDF was also found to reduce the PAI-1 activity
      in rats. Further, ADP-induced platelet aggregation was suppressed in PEDF-treated
      rats. The present study demonstrated first that PEDF exerted anti-hemostatic
      effects in rats, at least in part by suppressing PAI-1 activity and platelet
      aggregation. PEDF may be a novel therapeutic target for the treatment of patients
      with thrombogenic tendency and hypercoagulability.

PMID- 18815871
TI  - Improved self-exclusion program: preliminary results.
AB  - The gambling industry has offered self-exclusion programs for quite a long time.
      Such measures are designed to limit access to gaming opportunities and provide
      problem gamblers with the help they need to cease or limit their gambling
      behaviour. However, few studies have empirically evaluated these programs. This
      study has three objectives: (1) to observe the participation in an improved self
      exclusion program that includes an initial voluntary evaluation, phone support,
      and a mandatory meeting, (2) to evaluate satisfaction and usefulness of this
      service as perceived by self-excluders, (3) to measure the preliminary impact of
      this improved program. One hundred sixteen self-excluders completed a
      questionnaire about their satisfaction and their perception of the usefulness
      during the mandatory meeting. Among those participants, 39 attended an initial
      meeting. Comparisons between data collected at the initial meeting and data taken
      at the final meeting were made for those 39 participants. Data showed that
      gamblers chose the improved self-exclusion program 75% of the time; 25% preferred
      to sign a regular self-exclusion contract. Among those who chose the improved
      service, 40% wanted an initial voluntary evaluation and 37% of these individuals
      actually attended that meeting. Seventy percent of gamblers came to the mandatory
      meeting, which was a required condition to end their self-exclusion. The majority
      of participants were satisfied with the improved self-exclusion service and
      perceived it as useful. Major improvements were observed between the final and
      the initial evaluation on time and money spent, consequences of gambling, DSM-IV
      score, and psychological distress. The applicability of an improved self
      exclusion program is discussed and, as shown in our study, the inclusion of a
      final mandatory meeting might not be so repulsive for self-excluders. Future
      research directives are also proposed.

PMID- 18815872
TI  - Spectrofluorimetric determination of second critical micellar concentration of
      SDS and SDS/Brij 30 systems.
AB  - Potentially useful stead-state fluorimetric technique was used to determine the
      critical micellar concentrations (CMC(1) and CMC(2)) for two micellar media, one
      formed by SDS and the other by SDS/Brij 30. A comparative study based on
      conductimetric and surfacial tension measurements suggests that the CMC(1)
      estimated by the fluorimetric method is lower than the value estimated by these
      other techniques. Equivalent values were observed for SDS micelles without Brij
      30 neutral co-surfactant. The use of acridine orange as fluorescent probe
      permitted to determine both CMC(1) and CMC(2). Based on it an explanation on
      aspects of micelle formation mechanism is presented, particularly based on a
      spherical and a rod like structures.

PMID- 18815873
TI  - Effects of the HIV treatment drugs nevirapine and efavirenz on brain creatine
      kinase activity.
AB  - Nevirapine (NVP) and efavirenz (EFV) are antiretroviral drugs belonging to potent
      class of non-nucleoside reverse transcriptase inhibitors (NNRTIs) widely used for
      the treatment human immunodeficiency virus (HIV) infection. It has been
      demonstrated that NVP and EFV are able to cross the blood-brain barrier and
      arrive at the central nervous system (CNS), causing important adverse effects
      related to their presence within this tissue. Considering that the exact
      mechanisms responsible for CNS toxicity associated with NVP and EFV remain
      unknown and that creatine kinase (CK) plays an important role in cell energy
      homeostasis, in the present work we evaluated CK activity in brain of mice after
      chronic administration of these drugs. Our results demonstrated that NVP and EFV
      significantly inhibited CK activity in cerebellum, hippocampus, striatum and
      cortex of mice. Although it is difficult to extrapolate our findings to the human
      condition, the inhibition of brain CK activity by NVP and EFV may be associated
      with neurological adverse symptoms of these drugs.

PMID- 18815874
TI  - Successful cryoablation in the noncoronary aortic cusp for a left anteroseptal
      accessory pathway.
AB  - Catheter ablation of anteroseptal accessory pathways may be difficult because of
      the neighboring conduction tissue that may be damaged with ablation. We report a
      case of an accessory pathway localized to the anteroseptal region. A pathway
      potential found in the noncoronary cusp of the aortic valve was successfully
      targeted for ablation with cryo energy. Observations during tachycardia and
      pacing maneuvers suggest that the supravalvar aortic musculature may be an
      integral component of left anteroseptal pathways that can be safely targeted for
      cryoablation without injury of the atrioventricular conduction system.

PMID- 18815875
TI  - An ancient Indian method of penis lengthening.

PMID- 18815876
TI  - HIV and sexual risk behavior among commercial sex workers in the Netherlands.
AB  - In 2002-2005, a cross-sectional study to assess the potential for HIV
      transmission was carried out among 557 female and male-to-female transgender
      commercial sex workers (CSW) in three cities in the Netherlands. Female CSW (F
      CSW), drug-using female CSW (DU), and transgender sex workers were recruited in
      street-based and establishment-based sites. An anonymous questionnaire was
      administrated by interviewers and a saliva sample was collected for HIV antibody
      testing. The overall HIV prevalence was 5.7% (31/547; 10 samples were excluded
      because of "intermediate" test results). HIV was more prevalent among transgender
      (18.8%, 13/69) and DU (13.6%, 12/88) sex workers than among F-CSW (1.5%, 6/390).
      Of the HIV positive CSW, 74% were unaware of their infection. Consistent condom
      use with clients was 81%. Regular condom failure with clients was reported by
      39%. In multivariate analyses, transgender sex workers (OR = 22.9), drug-using
      CSW who ever injected drugs (OR = 31.1), African (OR = 19.0), and South European
      ethnicity (OR = 7.2) were independently associated with HIV. Condom failure (PRR
      = 2.0), anal sex (PRR = 2.1), and drug use (PRR = 3.8) were associated with
      inconsistent condom use with clients. There is a potential risk for further
      spread of HIV, through clients and (private) partners of sex workers, to the
      general population. Targeted health promotion activities are indicated for
      transgender sex workers and drug-using female CSW; active HIV testing must be
      continued.

PMID- 18815877
TI  - Perceived control and psychological distress in women with breast cancer: a
      longitudinal study.
AB  - The relationship between perceived control and psychological distress in cancer
      patients has been widely studied, but longitudinal designs are scarce. The aim of
      this study was to examine whether perceived control could predict changes in the
      evolution of psychological distress in breast cancer patients at stages I or II.
      One hundred and one women were assessed on five occasions: one week after
      surgery, and again 1, 3, 6 and 12 months later, using the Mental Adjustment to
      Cancer (MAC) Scale, a Self-Efficacy Scale, the Personal Competence Scale, the
      Hospital Anxiety and Depression Scale (HADS), the Profile of Mood Sates (POMS),
      and the EORTC questionnaire of quality of life. Latent growth curve (LGC) model
      analysis was used to test the relationship between perceived control and
      psychological distress in a longitudinal, 1-year study. The results showed that
      perceived control increases linearly and that distress also decreases linearly.
      Moreover, the evolution of distress can be predicted from the initial value and
      the rate of change of perceived control. This close relationship between
      perceived control and psychological distress was found to be independent of the
      evolution of the physical state. These findings suggest that perceived control
      could be used as an early predictor of psychological adjustment to illness.

PMID- 18815878
TI  - Size matters: community size, HIV stigma, & gender differences.
AB  - Conclusions regarding HIV stigma in rural areas are hampered by lack of agreement
      about rural classification. This investigation examined perceptions of HIV stigma
      among males and females with HIV/AIDS in metropolitan, micropolitan, and rural
      areas. Two-hundred people with HIV/AIDS completed a measure of perceived HIV
      stigma. Their county or town of residence was used to classify community size.
      Results indicated that community size was related to one aspect of perceived
      stigma, disclosure concerns, differently for men and women. Rural women reported
      more disclosure concerns than did metropolitan and micropolitan women. They also
      reported more disclosure concerns than rural men. Men in micropolitan communities
      reported more disclosure concerns than men in rural areas and tended to report
      more disclosure concerns than men in metropolitan areas. Understanding the
      relationship of community size to HIV stigmatization requires acknowledging that
      many communities are neither urban nor rural, and it requires considering gender
      differences.

PMID- 18815879
TI  - Metaplastic breast carcinomas are basal-like breast cancers: a genomic profiling
      analysis.
AB  - BACKGROUND: Metaplastic breast carcinomas (MBCs) comprise a group of aggressive
      and chemotherapy resistant cancers characterised by neoplastic cells displaying
      differentiation towards squamous epithelium or mesenchymal elements. Previous
      histopathological and immunohistochemical analysis of MBCs suggested that these
      cancers would have a basal-like profile. METHODS: We investigated the molecular
      subtype of 20 MBCs using microarray-based expression profiling data. These data
      were compared with those of 79 invasive ductal carcinomas (IDCs) of basal-like
      phenotype by unsupervised hierarchical clustering, supervised analysis and
      pathway analysis. RESULTS: We demonstrate that 95% of all MBCs are of basal-like
      molecular subtype. Furthermore, unsupervised hierarchical clustering analysis and
      pathway analysis of the profiles of MBCs revealed that MBCs are part of the
      spectrum of basal-like breast cancers. Significance analysis of microarrays (SAM)
      identified 1,385 transcripts differentially expressed between MBCs and IDCs of
      basal-like phenotype. Pathway analysis using these genes revealed that DNA repair
      pathways, including BRCA1 pathway, PTEN, a gene whose loss of function is
      associated with resistance to chemotherapy, and TOP2A, the molecular target of
      anthracyclines, are significantly downregulated in MBCs compared to basal-like
      IDCs. These findings may at least in part explain the reported poor responses to
      chemotherapy of MBCs. Furthermore, MBCs showed significantly higher expression of
      genes related to myoepithelial differentiation and epithelial to mesenchymal
      transition (EMT). CONCLUSIONS: Our results demonstrate that MBCs are part of the
      spectrum of basal-like breast carcinomas and display a myoepithelial and EMT-like
      molecular make-up. The reported poorer response to chemotherapeutic agents in
      patients with MBCs may stem from downregulated DNA damage response pathways, PTEN
      and TOP2A.

PMID- 18815880
TI  - Factors predicting in-breast tumor recurrence after breast-conserving surgery.
AB  - PURPOSE: The main objectives of this study were to identify risk factors for
      local in-breast tumor recurrence after breast-conservation and to evaluate the
      impact of IBTR (in-breast tumor recurrence) on overall survival. METHODS: A total
      of 335 consecutive patients with 346 invasive and in situ breast cancers were
      treated with breast conserving therapy. Univariate and multivariate statistical
      analysis were performed and survival rates were calculated and analyzed using the
      Kaplan-Meier method. RESULTS: With a median follow-up period of 70.6 months 14
      patients (4%) developed an IBTR. Overall survival and the disease-free 8-year
      actuarial survival of patients were 95% and 93%, respectively. The overall
      survival of patients with tumour recurrence on any site was significantly shorter
      than of those without recurrence (64% versus 85% after 8 years of follow-up; P <
      0.0001). Similarly, overall survival was significantly reduced in patients with
      distant metastases compared to all others without distant disease (88% versus 40%
      after 8 years; P < 0.0001). In contrast, overall survival of patients who
      experienced IBTR did not differ significantly from the group of patients who
      never developed IBTR (87% versus 70% after 8 years of follow-up). By univariate
      analysis, lobular carcinoma, high grade tumours, multifocality, concomitant LCIS
      and DCIS, the absence of estrogene and progesterone receptor status, as well as
      R1-status, were significant predictors of IBTR. By multivariate analysis, only R1
      status (P < 0.002) and the presence of LCIS around the invasive tumour (P < 0.03)
      remained as significant factors predicting IBTR. CONCLUSIONS: Concomitant lobular
      carcinomas in situ, as well as R1 surgical status are independent significant
      risk factors for in breast tumor recurrence after breast conserving therapy.

PMID- 18815881
TI  - Survivin plays as a resistant factor against tamoxifen-induced apoptosis in human
      breast cancer cells.
AB  - Tamoxifen has been the mainstay of endocrine therapy for estrogen receptor
      positive breast cancer. However, approximately 40% of breast cancer patients do
      not respond to tamoxifen treatment. Further, most tumors eventually acquire
      tamoxifen resistance. Therefore, it is necessary to develop effective modalities
      to enhance the efficacy of tamoxifen in breast cancer treatment. In this study,
      we investigated the mechanism by which breast cancer cells develop resistance
      against tamoxifen from the viewpoint of tamoxifen-induced apoptosis.
      Overexpression of the anti-apoptotic molecule survivin rendered the human breast
      cancer cells MCF-7 resistant to tamoxifen-induced apoptosis. To examine whether
      the down-regulation of survivin can enhance tamoxifen-induced apoptosis, we
      introduced siRNA targeting the survivin gene (survivin-siRNA) into MCF-7 cells.
      Survivin-siRNA transfection not only induced apoptosis without tamoxifen
      treatment but also augmented the tamoxifen-induced apoptosis. We have previously
      demonstrated that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors
      (HRIs), which are widely used to reduce the serum cholesterol levels in
      hypercholesterolemia patients, decreases survivin expression in colon cancer
      cells. To develop a pharmacological approach for improving the efficacy of
      tamoxifen treatment, we determined whether HRIs can enhance tamoxifen-induced
      apoptosis. Lovastatin, an HRI, down-regulated the expression of survivin protein
      in MCF-7 cells in a dose-dependent manner. In addition, the proportion of
      apoptotic cells induced by the tamoxifen and lovastatin combination was greater
      than the theoretical additive effect. These results suggest that survivin may
      function as a factor inducing resistance against tamoxifen-induced apoptosis, and
      the combined use of tamoxifen and HRI may be a novel approach to overcome
      tamoxifen resistance in breast cancer.

PMID- 18815882
TI  - Biochemical characterization of human and murine isoforms of UDP-N
      acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE).
AB  - The bifunctional enzyme UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine
      kinase (GNE) is the key enzyme for the biosynthesis of sialic acids, terminal
      components of glycoconjugates associated with a variety of physiological and
      pathological processes. Different protein isoforms of human and mouse GNE,
      deriving from splice variants, were predicted recently: GNE1 represents the GNE
      protein described in several studies before, GNE2 and GNE3 are proteins with
      extended and deleted N-termini, respectively. hGNE2, recombinantly expressed in
      insect and mamalian cells, displayed selective reduction of UDP-GlcNAc 2
      epimerase activity by the loss of its tetrameric state, which is essential for
      full enzyme activity. hGNE3, which had to be expressed in Escherichia coli, only
      possessed kinase activity, whereas mGNE1 and mGNE2 showed no significant
      differences. Our data therefore suggest a role of GNE1 in basic supply of cells
      with sialic acids, whereas GNE2 and GNE3 may have a function in fine-tuning of
      the sialic acid pathway.

PMID- 18815883
TI  - Screening for intestinal parasitic infections among Myanmar migrant workers in
      Thai food industry: a high-risk transmission.
AB  - The impact of intestinal parasitic infections on public health has been
      neglected. Millions of Myanmar natives have migrated to work in Thailand. We
      performed a study of intestinal parasitic infections in Myanmar-migrants working
      in the Thai food industry. A total of 338 Myanmar migrant workers in a food plant
      at Samut Sakhon Province, Thailand, were recruited for this study. 284 (84%)
      returned requested stool samples. Samples were examined for intestinal parasites
      by means of simple smear, formalin-ether concentration, Locke-Egg-Serum medium,
      and Harada-Mori culture methods. We found parasites in 177 (62.3%) migrants (29
      of 46 males; 148 of 238 females). The majority (89.3%) were infected with
      parasites transmitted by fecal-oral route, including Blastocystis hominis
      (41.5%), Trichuris trichiura (22.2%), Giardia lamblia (14.1%), and Ascaris
      lumbricoides (1.8%). Mixed infections were common (40.7%). The highest prevalence
      (73.3%) was found among migrants from Kohsong city, Myanmar. This high parasite
      infection rate in Myanmar migrant workers is an obvious public health hazard.

PMID- 18815884
TI  - An integrated fiberoptic-microfluidic device for agglutination detection and
      blood typing.
AB  - In this paper, an integrated fiberoptic-microfluidic device for the detection of
      agglutination for blood type cross-matching has been described. The device
      consists of a straight microfluidic channel through with a reacted RBC suspension
      is pumped with the help of a syringe pump. The flow intersects an optical path
      created by an emitter-received fiber optic pair integrated into the microfluidic
      device. A 650 nm laser diode is used as the light source and a silicon photodiode
      is used to detect the light intensity. The spacing between the tips of the two
      optic fibers can be adjusted. When fiber spacing is large and the concentration
      of the suspension is high, scattering phenomenon becomes the dominant mechanism
      for agglutination detection while at low concentrations and small spacing,
      optointerruption becomes the dominant mechanism. An agglutination strength factor
      (ASF) is calculated from the data. Studies with a variety of blood types indicate
      that the sensing method correctly identifies the agglutination reaction in all
      cases. A disposable integrated device can be designed for future implementation
      of the method for near-bedside pre-transfusion check.

PMID- 18815885
TI  - Controlling two-dimensional movement of microparticles over an electrode array
      surface.
AB  - This paper presents an original microchip device that manipulates planar x- and y
      positions of dielectric microbeads over an electrode array with dielectrophoresis
      (DEP) effects. Implemented with a simple single-layer metal process, the
      microchip device consists of two parallel arrays of triangular-shaped electrodes.
      The two arrays of electrodes are arranged such that they locked into each other
      to form interdigitated electrodes. The unique geometry and placement of the
      electrodes can produce different configurations of DEP waveforms. The different
      DEP waveforms will, in turn, allow the strength and the locations of the electric
      field maxima and minima to be manipulated. Our experiments showed that with a
      quad-pole traveling wave, the microbeads can be moved across the electrode array
      surface in directions parallel to the fluid flow to establish their x-positions
      via traveling wave dielectrophoresis (TWD) effect. In addition, the microbeads
      can be moved in directions perpendicular to the fluid flow to establish their y-
      positions via activating one or both sets of electrode arrays with DEP waveforms.
      A line of microbeads can be held indefinitely at the predetermined location or be
      immediately moved to an arbitrary location on the electrode array. With a
      functional transportation of particles along two planar axes, the "teeth-like"
      electrode structure can be easily integrated into a microfluidic system where an
      accurate position control of particles is required.

PMID- 18815886
TI  - Micro-electroporation of mesenchymal stem cells with alternating electrical
      current pulses.
AB  - Micro-electroporation is an electroporation technology in which the electrical
      field that induces cell membrane poration is focused onto a single cell contained
      in a micro-electromechanical structure. Micro-electroporation has many unique
      attributes including that it facilitates real time control over the process of
      electroporation at the single cell level. Flow-through micro-electroporation
      expands on this principle and was developed to facilitate electroporation of a
      large numbers of cells with control over the electroporation of every single
      cell. However, our studies show that when electroporation employs conventional
      direct current (DC) electrical pulses the micro-electroporation system fails,
      because of electrolysis induced gas bubble formation. We report in this study
      that when certain alternating currents (AC) electrical pulses are used for micro
      electroporation it becomes possible to avoid electrolytic gas bubble formation in
      a micro-electroporation flow-through system. The effect of AC micro
      electroporation on electrolysis was found to depend on the AC frequency used.
      This concept was tested with mesenchymal stem cells and preliminary results show
      successful electroporation using this system.

PMID- 18815887
TI  - Application of a numerical simulation to improve the separation efficiency of a
      sperm sorter.
AB  - This paper describes a study in which numerical simulations were applied to
      improve the separation efficiency of a microfluidic-based sperm sorter.
      Initially, the motion of 31 sperm were modeled as a sinusoidal wave. The modeled
      sperm were expected to move while vibrating in the fluid within the microchannel.
      In this analysis, the number of sperm extracted at the outlet channel and the
      rate of movement of the highly motile sperm were obtained for a wide range of
      flow velocities within the microchannel. By varying the channel height, and the
      width and the position of the sperm-inlet channel, we confirmed that the
      separation efficiency was highly dependent on the fluid velocity within the
      channel. These results will be valuable for improving the device configuration,
      and might help to realize further improvements in efficiency in the future.

PMID- 18815888
TI  - State of multicultural neuropsychological assessment in children: current
      research issues.
AB  - Scientific attention to cultural considerations in child neuropsychological
      assessment has not developed parallel to the focus these issues have received in
      adult and elderly neuropsychological assessment. There are limited data on the
      presence, magnitude, etiology, and implications of culture-related differences in
      cognitive test performance among children. This preliminary report reviews the
      available empirical literature on the current state of multicultural
      neuropsychological assessment in children. The review identified articles by
      searching PubMed and PsycINFO databases, and the tables of contents of
      Developmental Neuropsychology and Child Neuropsychology from 2003-2008. Of the
      1,834 abstracts reviewed, ten papers met inclusion criteria for the review. Five
      studies were completed in America; four of these compared performance between
      ethnic groups while the fifth examined neighborhood level poverty indicators
      exclusively within African-American children. Of the five international studies,
      all established local normative data and/or were exploratory investigations of
      neuropsychological functions in specific cultural groups, including Taiwanese
      infants, South African youth, and bilingual British children. Taken together, the
      results yield important clinical and research data that begin to inform many of
      the complex and fascinating mechanisms by which ethnic identity and culture
      impact cognitive development and the neuropsychological assessment of children. A
      critique of the existing literature and directions for future research are
      provided.

PMID- 18815890
TI  - CCL5/RANTES gene deletion attenuates opioid-induced increases in glial CCL2/MCP-1
      immunoreactivity and activation in HIV-1 Tat-exposed mice.
AB  - To assess the role of CC-chemokine ligand 5 (CCL5)/RANTES in opiate drug abuse
      and human immunodeficiency virus type 1 (HIV-1) comorbidity, the effects of
      systemic morphine and intrastriatal HIV-1 Tat on macrophage/microglial and
      astroglial activation were assessed in wild-type and CCL5 knockout mice. Mice
      were injected intrastriatally with vehicle or Tat and assessed after 7 days.
      Morphine was administered to some Tat-injected mice via time-release implant (5
      mg/day, s.c. for 5 days) starting at 2 days post injection. Glial activation was
      significantly reduced in CCL5(-/-) compared to wild-type mice at 7 days following
      combined Tat and morphine exposure. Moreover, the percentage of 3-nitrotyrosine
      immunopositive macrophages/microglia was markedly reduced in CCL5(-/-) mice
      injected with Tat +/- morphine compared to wild-type counterparts, suggesting
      that CCL5 contributes to nitrosative stress in HIV-1 encephalitis. In CCL5(-/-)
      mice, the reductions in Tat +/- morphine-induced gliosis coincided with
      significant declines in the proportion of CCL2/MCP-1-immunoreactive astrocytes
      and macrophages/microglia compared to wild-type counterparts. In knockout mice,
      neither Tat alone nor in combination with morphine increased the proportion of
      CCL2-immunoreactive astrocytes above percentages seen in vehicle-injected
      controls. Macrophages/microglia differed showing modest, albeit significant,
      increases in the proportion of CCL2-positive cells with combined Tat and morphine
      exposure, suggesting that CCL5 preferentially affects CCL2 expression by
      astroglia. Thus, CCL5 mediates glial activation caused by Tat and morphine,
      thereby aggravating HIV-1 neuropathogenesis in opiate abusers and non-abusers.
      CCL5 is implicated as mediating the cytokine-driven amplification of CCL2
      production by astrocytes and resultant macrophage/microglial recruitment and
      activation.

PMID- 18815891
TI  - Analysis of the protein expression profiling during rice callus differentiation
      under different plant hormone conditions.
AB  - Plant hormones function to coordinate plant growth and development. While the
      plant hormones, mainly auxin and cytokinin, are exogenously added to various
      plant tissue cultures, their effects on the organogenesis are apparent, but
      little is known concerning the molecular mechanisms by which they function in
      cultured cells. Rice, as a model plant in monocots, is also suitable to tissue
      culture studies. Here, we used four types of regeneration mediums with different
      relative concentrations of cytokinin and auxin for rice callus differentiation,
      the calli at different differentiation stages were collected for proteomic
      analysis. 2-dimensional electrophoresis revealed that 213 protein spots
      significantly differentially expressed during callus differentiation under
      different hormone conditions. By using mass spectrometry, 183 differentially
      expressed protein spots were identified to match 157 unique proteins. Most of
      these differential proteins were cellular/metabolic process-related proteins,
      whose different expression patterns may be correlated with the cytokinin and
      auxin regulation. Several hormone-related proteins were prominently featured in
      differentiated calli as compared with the initiated calli, such as alpha-amylase
      isoforms, mannose-binding rice lectin, putative dehydration stress-induced
      protein, cysteine endopeptidase and cystatin. All these results provide a novel
      insight into how the two plant hormones effect the callus differentiation in rice
      on the proteomic level.

PMID- 18815889
TI  - Lifecourse social conditions and racial and ethnic patterns of cognitive aging.
AB  - A lifecourse perspective is key for understanding and interpreting racial and
      ethnic patterns in neuropsychological test performance. In this article, we
      discuss contextual factors that shape the environmental conditions encountered by
      racial and ethnic minorities in the United States, in particular African
      Americans. These conditions include geographic segregation at the level of
      regions, metropolitan areas, and neighborhoods; intra- and inter-national
      migration patterns; socioeconomic position, including financial resources, and
      occupational and educational opportunities; discrimination; and group resources.
      Each of these exposures sets in course a cascade of individual mediators that
      ultimately manifest in neuropsychological outcomes. The physiological and
      behavioral consequences of these pathways likely accumulate across the
      lifecourse. We focus on cognitive aging, although the processes discussed here
      begin in infancy and likely influence cognitive outcomes throughout life from
      childhood into old age. A lifecourse framework can help inform clinical
      encounters, neuropsychological research, and surveillance regarding the
      population prevalence of cognitive impairments.

PMID- 18815892
TI  - Comparative analysis of distinct non-coding characteristics potentially
      contributing to the divergence of human tissue-specific genes.
AB  - To further elucidate the characteristics and potential functions of non-coding
      region of certain genes, we here systematically examined alternative promoter
      regions and repeated elements in non-coding regulatory regions of human tissue
      specific genes. The results demonstrated that the different types of tissue
      specific gene show distinct characteristics, such as the type of alternative
      promoters, CpG islands, initiating intervallic dinucleotides, and repeat
      elements. Surprisingly, 74.8% of selected genes contain more than one putative
      alternative promoter (PAP), and about 92.11% of signal receptors (membrane-bound)
      possess PAPs. Moreover, a specific PAP type (GC-GC type: both the downstream
      (+300) and the upstream (-700) regions of transcription start sites are GC-rich)
      is dominant in human tissue-specific genes and the tissue-specific transcription
      factors have significantly higher proportion of GC-GC type PAPs. Notably, our
      data indicated that more than 80% of PAPs are CpG-poor in the considered genes.
      Furthermore, our findings revealed an inverse tendency between transposable
      elements and other repeated elements in the 5' flanking regions. These results
      seem to imply that the distinct alternative promoters and repeated elements may
      contribute to the regulation and divergence of human tissue-specific genes.

PMID- 18815893
TI  - Comparative analysis of mitochondrial control region in polyploid hybrids of red
      crucian carp (Carassius auratus) x blunt snout bream (Megalobrama amblycephala).
AB  - The entire sequences of the mitochondrial (mt)DNA control region (CR) and
      portions of its flanking genes in the red crucian carp (RC) and blunt snout bream
      (BSB) as well as their polyploid hybrids (3nRB, 4nRB and 5nRB) were determined
      and subjected to a comparative analysis. The mtDNA-CRs of these five fish species
      ranged from 923 to 937 bp in length, they had the same flanking gene arrangement
      as other vertebrates and the pattern of nucleotide substitution bias was also
      similar to that in other vertebrates. Our data are consistent with the viewpoint
      of three domains [extended terminal associated sequence (ETAS domain), central
      conserved sequence block domain and conserved sequence block (CSB) domain] within
      the mtDNA-CR of mammals. On the basis our comparative analysis of the mtDNA-CRs
      of these five fish species, we were able to identify the consensus sequences of
      functional conserved units, including the ETAS, CSB-F, CSB-D, CSB-E, CSB1, CSB2
      and CSB3 and putative promoter. The percentage of variable nucleotide positions
      (41.98%) in the central domain was lower than those in the ETAS and conserved
      domain (71.70 and 47.12%, respectively), suggesting that the central domain was
      the most conserved part of the mtDNA-CR. These results provide useful and
      important information for the further study of mtDNA-CR structure in fish. The
      sequence similarities of mtDNA-CR among the 3nRB, 4nRB, 5nRB hybrids and their
      respective female parents were higher than those among the 3nRB, 4nRB, 5nRB
      hybrids and their respective male parents, providing the direct evidence of
      stringent maternal inheritance of mtDNA-CR in the 3nRB, 4nRB and 5nRB hybrids.

PMID- 18815894
TI  - Goat farming systems in Martinique: management and breeding strategies.
AB  - To be successful, initiatives to improve farmer's goat production should directly
      address the needs and objectives of the keepers while promoting rational use of
      local genetic resources. A survey was carried out to implement a genetic policy
      governing meat goat farming in Martinique (11,400 heads and 33,400 ha arable
      land). The questionnaire comprised a total of 27 items with 306 modalities, and
      included questions on farm structure, crop and animal productions, management of
      feeding, reproduction and health control. The sample consisted of 33 farmers with
      644 ha and 2,680 goats (1,286 does and 52 bucks), 97% of does in the studied
      sample were crossbred, 56% of bucks were" imported" breeds (Boer or Anglo
      Nubian). The number of goats per farm varied from 16 to 582. The feeding system
      was predominantly grazing, according to a rotation (55% of cases) or continuous
      grazing system (42%). On 62% of farms, the males remained with the females
      permanently, also 83% of farmers did not resort to methods of controlled-mating.
      The first criteria used for choosing animals (80 to 90% of answers) of both sex,
      were development and conformation. Assuming that adaptive together with
      productive traits are important in tropical zones, it is advisable to better
      define the maternal lineage of the local livestock (presently very sparse
      records), to improve reproduction management and culling strategies (poor and
      inadequate management practices do not support any genetic improvement
      programme), and to guide the farmers in their decisions by employing concerted
      interprofessional actions (choice of meat breed, market studies).

PMID- 18815896
TI  - Stress goes Far East: meeting report of the Sixth International Workshop on the
      Molecular Biology of Stress Responses.

PMID- 18815895
TI  - Mitochondrial DNA variability modulates mRNA and intra-mitochondrial protein
      levels of HSP60 and HSP75: experimental evidence from cybrid lines.
AB  - To explore possible relationships between mitochondrial DNA (mtDNA) polymorphism
      and the expression levels of stress-responder nuclear genes we assembled five
      cybrid cell lines by repopulating 143B.TK(-) cells, depleted of their own mtDNA
      (Rho(0) cells), with foreign mitochondria with different mtDNA sequences (lines
      H, J, T, U, X). We evaluated, at both basal and under heat stress conditions,
      gene expression (mRNA) and intra-mitochondrial protein levels of HSP60 and HSP75,
      two key components in cellular stress response. At basal conditions, the levels
      of HSP60 and HSP75 mRNA were lower in one cybrid (H) than in the others (p =
      0.005 and p = 0.001, respectively). Under stress conditions, the H line over
      expressed both genes, so that the inter-cybrid difference was abolished.
      Moreover, the HSP60 intra-mitochondrial protein levels differed among the cybrid
      lines (p = 0.001), with levels higher in H than in the other cybrid lines. On the
      whole, our results provide further experimental evidence that mtDNA variability
      influences the cell response to stressful conditions by modulating components
      involved in this response. Sentence summary of the article: the results reported
      in the present study provide important experimental evidence that in human cells
      mtDNA variability is able to influence the cellular response to heat stress by
      modulating both the transcription of genes involved in this response and their
      intra-mitochondrial protein levels.

PMID- 18815897
TI  - Taxonomic revision and phylogenetic analysis of the cestode genus
      Paraprogynotaenia Rysavy, 1966 (Cyclophyllidea: Progynotaeniidae).
AB  - The type-series of Paraprogynotaenia jimenezi Rysavy, 1966 [type-species of
      Paraprogynotaenia Rysavy, 1966] from Charadrius wilsonia Ord in Cuba and P.
      charadrii (Yamaguti, 1956) (= Proterogynotaenia charadrii Yamaguti, 1956) from C.
      alexandrinus L. in Japan are redescribed. Two new species are described:
      Paraprogynotaenia minuta n. sp. from C. alexandrinus on the Black Sea coast of
      Bulgaria [type-host and type-locality, based on specimens previously reported as
      P. charadrii], from the same host species in Tunisia and from "Tringa totanus"
      (the host identification is uncertain) in France [the latter two samples were
      previously reported as Progynotaenia odhneri Nybelin, 1916]; and
      Paraprogynotaenia canarisi n. sp. from C. marginatus Vieillot in the Republic of
      South Africa [type-host and type-locality] and from C. alexandrinus and Pluvialis
      dominica (Muller) in Taiwan [specimens from both localities were previously
      reported as Paraprogynotaenia charadrii]. P. jimenezi can be distinguished from
      its congeners by having 12 hooks of equal length. Among the remaining species
      with 18-22 hooks of varying length, P. minuta n. sp. can be distinguished by the
      smaller number of proglottides: up to 8 vs 15-20 for P. charadrii and P. canarisi
      n. sp. The latter two species can be differentiated from one another by the blade
      length/total length ratio of the smallest (lateral) rostellar hooks, which is
      less than 0.5 for P. canarisi n. sp. and 0.5 or more for P. charadrii. An
      identification key to the species of Paraprogynotaenia is provided and the
      generic diagnosis is amended. A phylogenetic analysis based on 17 morphological
      characters resulted in the following hypothesis for the relationships within the
      genus: (P. jimenezi (P. minuta (P. charadrii, P. canarisi))).

PMID- 18815898
TI  - Mathevotaenia niuguiniensis n. sp. (Cestoda: Anoplocephalidae: Linstowiinae) from
      the water-rat Parahydromys asper (Thomas) in Papua New Guinea, with a list of
      species of Mathevotaenia Akumyan, 1946.
AB  - A new species of cestode, Mathevotaenia niuguiniensis n. sp. (Anoplocephalidae:
      Linstowiinae), is described from the hydromyine rodent Parahydromys asper
      (Thomas) in Papua New Guinea. This is the third species of the genus reported
      from the Australasian region. The new species differs from all congeners in
      rodents by having an elongate cirrus-sac, which crosses the osmoregulatory canals
      and extends into the medulla, compared with a short, ovoid cirrus-sac which does
      not penetrate into the medulla in congeners. It differs from the known Australian
      species, M. antechini (Beveridge, 1977) and M. nyctophili (Hickman, 1954), found
      in dasyurid marsupials and bats respectively, by lacking a complex of
      anastomosing osmoregulatory canals in each segment. A list of all known species
      of Mathevotaenia Akumyan, 1946, their host genera, host families and geographical
      distribution is provided. New combinations proposed in this report are: M.
      dipodomi (Bienek & Grundmann, 1973) n. comb. (transferred from Schizorchodes
      Bienek & Grundman, 1973), M. genettae (Ortlepp, 1937) n.comb., M. mephitis
      (Skinker, 1935) n. comb., M. pedunculata (Chandler, 1952) n. comb., M. wallacei
      (Chandler, 1952) n. comb. (transferred from Oschmarenia Spasskii, 1951) and M.
      oedipomidatis (Stunkard, 1965) n. comb. (transferred from Paratriotaenia
      Stunkard, 1965).

PMID- 18815899
TI  - Longidorus kheirii n. sp. (Nematoda: Longidoridae) from Iran.
AB  - Longidorus kheirii n. sp., a parthenogenetic species, was found in soil samples
      collected from the rhizosphere of Rosa sp. growing in a natural mountainous
      region close to Maragheh city, northwestern Iran. It is characterised by having a
      long body (6.7-9 mm), a 19.5-23 mum wide head continuous with the body contour, a
      truncate and slightly concave lip region with convex sides between the anterior
      end and the guide-ring, an odontostyle 113-130 mum long, an odontophore 69-97.5
      mum long, a body width of 90.5-117.5 mum at the mid-body, a long, wide
      oesophageal bulb (149.5-193.5 x 39.5-48 mum), a tail length of 47-72 mum, a male
      with 11 ventromedian supplements and spicules of 85 mum in length, and four
      juvenile stages. The ribosomal 18S rDNA gene of L. kheirii n. sp., L.
      leptocephalus Hooper, 1961, L. profundorum Hooper, 1966 L. euonymus Mali &
      Hooper, 1973 and two unidentified species listed as Longidorus sp. 1 and
      Longidorus sp. 2, all recovered from northwestern Iran in the same survey, and
      the ITS1 of L. kheirii n. sp. and Longidorus sp. 1 were sequenced in order to
      investigate the phylogenetic relationships with other previously sequenced
      Longidorus species.

PMID- 18815900
TI  - Two new species of Paraorygmatobothrium Ruhnke, 1994 (Tetraphyllidea:
      Phyllobothriidae) from the smooth-hound Mustelus mustelus (L.) and the gummy
      shark M. antarcticus Gunther (Carcharhiniformes: Triakidae).
AB  - Two new tetraphyllidean species, Paraorygmatobothrium bai n. sp. and P. rodmani
      n. sp., are described from the smooth-hound shark Mustelus mustelus (Linnaeus)
      and the gummy shark M.s antarcticus Gunther, respectively. The two species are
      generally consistent in morphology with the nine existing species of
      Paraorygmatobothrium Ruhnke, 1994. P. bai n. sp. and P. rodmani n. sp. differ
      from the existing species of Paraorygmatobothrium in exhibiting gravid
      proglottids on the strobila. P. bai n. sp. differs from P. rodmani n. sp. in
      testicular shape and number, in addition to significant differences in body
      length, and terminal and subterminal proglottis length to width ratios.
      Description of these two new species increases the known number of species of
      Paraorygmatobothrium to 11.

PMID- 18815901
TI  - Two new species of Eimeria Schneider, 1875 (Apicomplexa: Eimeriidae) from
      Gerbilliscus guineae Thomas (Rodentia: Gerbillinae) in the Niokolo Koba National
      Park, Senegal.
AB  - We describe two new species of Eimeria Schneider, 1875 from the gerbiline rodent
      Gerbilliscus guineae in the Niokolo Koba National Park, Senegal. Faecal
      examination of samples revealed the presence of sporulated oocysts of two
      eimerian coccidia, both possessing an oocyst residuum. Eimeria permira n. sp. is
      remarkable in terms of oocyst size and oocyst wall texture. Sporulated oocysts
      are ellipsoidal, 45.8 (42-50) x 32.5 (31-38) mum; the oocyst wall is 3-4 mum
      thick, composed of three layers, with the outer layer sheathed by rough granular
      material; and the sporocysts are broadly ellipsoidal, 15.4 (15-16) x 11 and with
      a Stieda body present. Oocysts of Eimeria gerbillisci n. sp. are subspherical,
      22.5 (19.5-24) x 18.8 (16.5-20) mum, with a colourless, faintly granulated oocyst
      wall 1.5 thick; and the sporocysts are 10.1 (10-12) x 6.7 (6-8), broadly
      ellipsoidal and often somewhat pointed towards both ends.

PMID- 18815902
TI  - Proctocaecum gairhei n. sp. (Digenea: Cryptogonimidae: Acanthostominae) from
      Gavialis gangeticus (Gmelin) in Nepal and a revised cladogram of Proctocaecum
      Baugh, 1957.
AB  - Proctocaecum gairhei n. sp. is described from the gharial Gavialis gangeticus
      (Gmelin) in Nepal. The new taxon can be distinguished from all other species of
      Proctocaecum Baugh, 1957 by the combination of the following morphological
      characters: a single row of 23 cephalic spines, lateral anal pores opening at
      uneven levels, a forebody accounting for 16% of the total body length (TBL), an
      oral to ventral sucker width ratio of 1:0.7, an oral sucker to pharynx width
      ratio of 1:0.6 and uterine loops that occupy 59-67% of the TBL. While sharing
      some morphological characteristics with Acanthostomum slusarskii Kalyankar, 1977
      from Crocodylus palustris (Lesson) in India, P. gairhei n. sp. is distinguished
      from the latter by possessing the solid muscular gonotyl diagnostic for
      Proctocaecum, by the number of cephalic spines, position of the anal pores and
      egg size. The existing cladogram for Proctocaecum was expanded using the
      character information of P. gairhei n. sp. The host range of Proctocaecum is now
      known to include all three families of the order Crocodylia.

PMID- 18815903
TI  - Degradation of phytates in distillers' grains and corn gluten feed by Aspergillus
      niger phytase.
AB  - Distillers' dried grains with solubles (DDGS) and corn gluten feed (CGF) are
      major coproducts of ethanol production from corn dry grind and wet milling
      facilities, respectively. These coproducts contain important nutrients and high
      levels of phytates. The phytates in these products cannot be digested by
      nonruminant animals; consequently, large quantities of phytate phosphorus (P) are
      deposited into the soil with the animal wastes which potentially could cause P
      pollution in soil and underground water resources. To reduce phytates in DDGS and
      CGF, a phytase from Aspergillus niger, PhyA, was investigated regarding its
      capability to catalyze the hydrolysis of phytates in light steep water (LSW) and
      whole stillage (WS). LSW and WS streams are the intermediate streams in the
      production of CGF and DDGS, respectively, and contribute to most of the P in
      these streams. Enzyme loadings with activity of 0.1, 1, 2, and 4 FTU/g substrate
      and temperatures of 35 and 45 degrees C were investigated regarding their
      influences on the degree of hydrolysis. The analysis of the hydrolyzate suggested
      to a sequentially degradation of phytates to lower order myo-inositol phosphate
      isomers. Approximately 90% phytate P of LSW and 66% phytate P of WS were
      released, suggesting myo-inositol monophosphate as the end product. The maximum
      amount of released P was 4.52 +/- 0.03 mg/g LSW and 0.86 +/- 0.01 mg/g WS.

PMID- 18815904
TI  - Purification and characterization of a glycoside hydrolase family 43 beta
      xylosidase from Geobacillus thermoleovorans IT-08.
AB  - The gene encoding a glycoside hydrolase family 43 beta-xylosidase (GbtXyl43A)
      from the thermophilic bacterium Geobacillus thermoleovorans strain IT-08 was
      synthesized and cloned with a C-terminal His-tag into a pET29b expression vector.
      The recombinant gene product termed GbtXyl43A was expressed in Escherichia coli
      and purified to apparent homogeneity. Michaelis-Menten kinetic parameters were
      obtained for the artificial substrates p-nitrophenyl-beta-D: -xylopyranose (4NPX)
      and p-nitrophenyl-alpha-L: -arabinofuranose (4NPA), and it was found that the
      ratio k (cat)/K (m) 4NPA/k (cat)/K (m) 4NPX was approximately 7, indicting
      greater catalytic efficiency for 4NP hydrolysis from the arabinofuranose aglycon
      moiety. Substrate inhibition was observed for the substrates 4-methylumbelliferyl
      xylopyranoside (muX) and the arabinofuranoside cogener (muA), and the ratio k
      (cat)/K (m) muA/k (cat)/K (m) muX was approximately 5. The enzyme was
      competitively inhibited by monosaccharides, with an arabinose K (i) of 6.8 +/-
      0.62 mM and xylose K (i) of 76 +/- 8.5 mM. The pH maxima was 5.0, and the enzyme
      was not thermally stable above 54 degrees C, with a t (1/2) of 35 min at 57.5
      degrees C. GbtXyl43A showed a broad substrate specificity for hydrolysis of
      xylooligosaccharides up to the highest degree of polymerization tested
      (xylopentaose), and also released xylose from birch and beechwood arabinoxylan.

PMID- 18815905
TI  - Optimization of RNA isolation from Brittle Leaf Disease affected date palm leaves
      and construction of a subtractive cDNA library.
AB  - A simple and efficient method was described here for the isolation of high
      quality RNA from date palm leaves affected with Brittle Leaf Disease (BLD) and
      containing high amount of phenolic compounds. The procedure was based on the use
      of a non-ionic detergent Nonidet-P40 (NP-40), Polyvinylpyrrolidone (PVP), and
      beta-mercaptoethanol in the extraction buffer in order to isolate cytoplasmic RNA
      and to prevent the oxidation of phenolic compounds. This method allowed the
      isolation of intact RNA, suitable for cDNA synthesis and library construction.
      Differential screening of the subtractive cDNA library from affected leaf RNA led
      to the identification of some BLD-induced genes.

PMID- 18815907
TI  - [Clinical prevalence and reason for visit of patients with generalized anxiety
      disorder seen in the psychiatry out-patient clinics in Spain. Results of the
      LIGANDO study].
AB  - INTRODUCTION: Generalized anxiety disorder (GAD) is frequent and has a great
      impact on quality of life. Its prevalence in the general population and in
      primary care has been established previously in Spain; however it still must be
      determined in the mental health. METHODS: An epidemiological, multicenter and
      cross-sectional study was carried out, collecting demographic data, reason for
      consultation and presence of GAD diagnosis according to ICD-10 criteria of their
      first 75 visiting patients on a randomly selected representative sample of 312
      psychiatrists. RESULTS: Data from 20,347 subjects was recorded. Clinic prevalence
      of GAD was 13.7% (95% confidence interval: 13.3-14.2). The most frequent reason
      for psychiatric consultation was depressive symptoms (26.7%) followed by symptoms
      of anxiety (18.2%). In 71.4% of GAD patients, the reason for consultation was
      anxiety symptoms. CONCLUSIONS: GAD clinic prevalence in Spain is high. Almost one
      out of three GAD-patients visits the psychiatrist office for a reason other than
      this condition.

PMID- 18815908
TI  - Study of personality disorders and the use of services in the clinical population
      attended in the mental health network of a community area.
AB  - INTRODUCTION: Personality disorders (PD) are a growing clinical and health care
      problem. In Spain, the studies of PD and utilization of the Mental Health
      Services (MHS) in the clinical population are scant. However, these data are
      necessary in the planning of MHS for PD. METHOD: We studied all the patients
      attended throughout one year in all the psychiatric departments (n=2701), and
      separately in the inpatient (n=193) and outpatient (n=2649) psychiatric services.
      All the patients diagnosed with PD by clinical interview (DSM-IV-TR criteria)
      were included. Demographic and clinical variables as well as use of MHS were
      studied. RESULTS: The proportion of PD in the population attended was 11% (95%
      CI: 9.8%-12.2%) and in the inpatient and outpatient psychiatric services 17.6%
      (95% CI: 12.9%- 23.6%) and 10.3% (95% CI: 9.2%-11.5%), respectively. The most
      representative PD were borderline (25.7%), histrionic (24%) and obsessive
      compulsive (6.4%) and 19.6% were not otherwise specified PD. PD accounted for an
      extensive use of mental health resources (inpatient, outpatient and emergency
      units). The most comorbid conditions in axis I were affective, anxiety and
      substance-related disorders. CONCLUSIONS: The study of PD attended in the MHS in
      a community area by means of clinical evaluation is an economical instrument,
      which is easily applied and replicated in planning of MHS for PD.

PMID- 18815911
TI  - Bladder cancer: from pathogenesis to prevention.

PMID- 18815912
TI  - Chairmen's summary.

PMID- 18815913
TI  - The epidemiology of bladder cancer in Russia.
AB  - This study assessed the epidemiology of bladder cancer in Russia. The available
      publications in Russian were analysed, as well as information from the database
      of N. N. Blokhin Cancer Research Center, accumulating non-uniform data from
      different cities and regions of Russia. In 2006 there were 68 129 patients with
      bladder cancer in Russia, accounting for 2.8% of all cancer cases, with unknown
      proportions of males and females. In the same year 11 973 new bladder cancer
      cases were diagnosed, with morphological confirmation in 82.3% of cases. From
      1999 to 2004 the incidence of bladder carcinoma increased by 5.3% in males and by
      12.5% in females. In 2006 57.4% of patients with newly diagnosed disease were
      staged as T1 and T2, 26.8% as T3 and 11.4% as T4 bladder cancer cases. The
      mortality rate of patients with bladder carcinoma increased by 10.9% in males
      from 1999 to 2004 and did not change in females. In conclusion, over the past 10
      years both the prevalence and incidence of bladder carcinoma have increased in
      Russia. There was a trend towards detecting less advanced cases of the disease,
      and stages T3 and T4 are diagnosed less frequently today than in 1996. As a
      result the mortality rate of bladder cancer patients within the first year from
      diagnosis has decreased, although the overall mortality rate in males has risen.

PMID- 18815914
TI  - Nutrition, total fluid and bladder cancer.
AB  - Bladder cancer is a major health concern for older males in Western populations.
      About 30 years ago there was a suggestion that nutrition may have a role in the
      aetiology of the disease. Although the literature has been accumulating since
      then, owing to heterogeneity between studies results have often been inconsistent
      and unclear. The aim of this paper was to present an updated summary of the
      scientific evidence on the association between nutrition, total fluid intake and
      bladder cancer. A search of computerized databases, PubMed, ISI, Embase and
      Cochrane Library, was conducted to identify all epidemiological studies published
      between 1966 and October 2007. The level of scientific evidence for the various
      nutritional factors and total fluid intake was ranked according to the number of
      studies reporting a statistically significant association and the existence of
      mechanistic evidence. The levels of association were based on a ranking of
      statistically significant relative risks. Fruit and yellow-orange vegetables,
      particularly carrots and selenium, are probably associated with a moderately
      reduced risk of bladder cancer. Citrus fruits and cruciferous vegetables were
      also identified as having a possible protective effect. Possible risk factors are
      salted and barbecued meat, pork, total fat, pickled vegetables, salt, soy
      products, spices and artificial sweeteners. No clear association could be
      determined for beef, eggs, processed meats and total fluid intake. In conclusion,
      specific fruit and vegetables may act to reduce the risk of bladder cancer.
      Future studies on bladder cancer should investigate the effect of food
      categorization, amount and gender.

PMID- 18815915
TI  - Coffee and alcohol consumption and bladder cancer.
AB  - Epidemiological studies on coffee, alcohol and bladder cancer risk published up
      to 2007 were reviewed. Coffee drinkers have a moderately higher relative risk of
      bladder cancer compared to non-drinkers. The association may partly be due to
      residual confounding by smoking or dietary factors, but the interpretation
      remains open to discussion, although the absence of dose and duration-risk
      relations weighs against the presence of a causal association. Most studies of
      alcohol and bladder cancer found no association, with some studies finding a
      direct and other an inverse one. This again may be due to differential
      confounding effect of tobacco smoking--the major risk factor for bladder cancer-
      in various populations. Thus, epidemiological findings on the relation between
      alcohol drinking and bladder cancer exclude any meaningful association.

PMID- 18815916
TI  - Tobacco smoking and risk of bladder cancer.
AB  - Tobacco smoking is the main known cause of urinary bladder cancer in humans. In
      most populations, over half of cases in men and a sizeable proportion in women
      are attributable to this habit. Epidemiological studies conducted in different
      populations have shown a linear relationship between intensity and duration of
      smoking and risk. Quitting smoking reduces the risk of bladder cancer. Smoking
      black (air-cured) cigarettes results in a higher risk than smoking blond (flue
      cured) tobacco cigarettes; results on inhalation patterns and use of filter are
      not consistent. Cigar and pipe smoking also increases the risk of bladder cancer;
      data on other tobacco products are limited. The evidence for non-transitional
      bladder carcinoma is limited, but consistent with an increased risk. The
      available evidence does not point towards a different carcinogenic effect of
      tobacco smoking in men and women or in whites and blacks. Data on involuntary
      smoke and use of smokeless tobacco products are limited, but do not suggest an
      increased risk of bladder cancer.

PMID- 18815917
TI  - Smoking prevention: obstacles and possibilities.
AB  - A brief overview is given of the disastrous effects of tobacco smoking on health,
      the environment and the economy. Obstacles for prevention are exemplified by the
      strong addictive property of nicotine, the ruthlessness and greed of the tobacco
      industry, and the ambivalence still demonstrated by the political and the health
      professional community in the fight against tobacco. A successful comprehensive
      tobacco control strategy is recognized and promoted by the first global health
      convention, the World Health Organization (WHO) Framework Convention on Tobacco
      Control. WHO has great expectations of the health community to support the
      implementation of the convention: who else has a greater responsibility?

PMID- 18815918
TI  - Occupational risk factors.
AB  - The association between exposure to selected chemical carcinogens, occupations or
      industries and bladder cancer is well established, and it is estimated that 20
      27% of bladder cancers are attributable to occupational exposures. The risk of
      bladder cancer stemming from an occupational exposure depends not only on
      compound carcinogenicity, exposure intensity and workplace characteristics, but
      also on individual susceptibility to these cancers. Regulatory controls in
      industrialized nations have resulted in a decreased burden of exposure to bladder
      carcinogens in the workplace. Unfortunately, the same is unlikely in many
      developing countries, where risky technologies may have been transferred from
      more developed countries, and where enforcement of regulations and worker
      protection are likely to be less stringent.

PMID- 18815919
TI  - A meta-analysis on the association between bladder cancer and occupation.
AB  - To date, many epidemiological studies have been conducted to examine the
      association between occupation and bladder cancer incidence. However, results
      from these studies often have been inconsistent, and significant associations
      have rarely been found, possibly owing to the lack of adequate statistical power
      in these studies. This meta-analysis summarizes the relevant literature regarding
      occupation and bladder cancer incidence to increase the statistical power to
      detect associations. The Medline and Embase databases were searched to retrieve
      epidemiological studies published up until May 2008. Individual risk estimates
      for subjects with an employment history in the occupation of interest were
      extracted from each included publication. For each occupation, a summary relative
      risk (SRR) was calculated by means of a random effects model. Significantly
      increased risks with an SRR greater than 1.20 were identified for miners
      [SRR=1.31, 95% confidence interval (CI) 1.09-1.57], bus drivers (SRR=1.29, 95% CI
      1.08-1.53), rubber workers (SRR=1.29, 95% CI 1.06-1.58), motor mechanics
      (SRR=1.27, 95% CI 1.10-1.46), leather workers (SRR=1.27, 95% CI 1.07-1.49),
      blacksmiths (SRR=1.27, 95% CI 1.02-1.58), machine setters (SRR=1.24, 95% CI 1.09
      1.42), hairdressers (SRR=1.23, 95% CI 1.11-1.37) and mechanics (SRR=1.21, 95% CI
      1.12-1.31). In conclusion, the studies reviewed provide consistent support for a
      small but significant increased risk of bladder cancer among workers in these
      nine occupations. Although the relative risk of bladder cancer associated with
      these occupations is small, the public health impact may be significant,
      considering the substantial number of people who were and are employed in these
      occupations.

PMID- 18815920
TI  - Infection: is it a cause of bladder cancer?
AB  - This article reviews the literature regarding the possible correlation between
      infection and occurrence of bladder cancer. The PubMed literature database was
      searched from inception to January 2008. Keywords of bladder, cancer, parasitic,
      bacterial, viral and infection, were used. Forty studies were included in the
      review. Several investigators support the idea that schistosomiasis is
      aetiologically related to the development of bladder cancer in individuals
      infected with Schistosoma haematobium. Approximately 70% of those with chronic
      schistosomiasis who have bladder cancer develop squamous cell rather than
      transitional cell carcinoma. Several investigators suggest that bacteria may play
      a role in inducing bladder cancer. Clinically, researchers have linked the
      development of infection, urinary stones and indwelling catheters with bladder
      cancer. Nevertheless, to date, no prospective study has examined the association
      between urinary tract infection and bladder cancer risk. The possibility that
      infection by human papilloma virus (HPV) is a risk factor contributing to bladder
      cancer has been investigated but no definite conclusions have been drawn. Thus,
      the debate remains open as to whether there is any direct link between chronic
      HPV infection and bladder cancer. Only 15 cases of vesical carcinoma have been
      reported, to date, in the setting of human immunodeficiency virus (HIV). The rare
      occurrence of bladder cancer during HIV infection and the lack of correlation
      with the laboratory markers of HIV disease progression may suggest a trivial
      association between two unrelated disorders. BK virus is oncogenic in newborn
      hamsters and can transfer to mammalian cells in vitro, but there is little
      consistent evidence of a link with human bladder cancer. Studies showed no
      correlation between herpes simplex virus (HSV) and bladder cancer, but bladder
      cancer becomes infected with HSV much more easily than non-neoplastic urothelium.
      In conclusion, with the exception of chronic infection with S. haematobium, the
      association between the occurrence of bladder cancer and chronic bacterial or
      viral infections could not be confirmed. Prospective studies with large numbers
      of patients and controls are required to confirm this issue.

PMID- 18815921
TI  - Radiation-associated urinary bladder cancer.
AB  - A few data sets have been used for assessing the risk of radiation-associated
      bladder cancer. The most important are the Japanese atomic bomb survivors and
      patients exposed to ionizing radiation for medical purposes. According to a
      report from the United Nations Commission on the Effect of Ionizing Radiation,
      there is convincing evidence of a relationship between exposure to ionizing
      radiation and bladder cancer. In contrast to many other malignancies it is not
      clear how age at exposure and gender affect the risk of bladder cancer.
      Furthermore, the potential interaction between smoking and radiation exposure
      needs to be studied in greater detail.

PMID- 18815922
TI  - Chemotherapy-induced bladder cancer.

PMID- 18815923
TI  - Bladder cancer: pathogenesis.

PMID- 18815924
TI  - Bladder cancer: clinical and pathological profile.
AB  - Bladder tumours represent a heterogeneous group of cancers. The natural history
      of these bladder cancers is that of recurrence of disease and progression to
      higher grade and stage disease. Furthermore, recurrence and progression rates of
      superficial bladder cancer vary according to several tumour characteristics,
      mainly tumour grade and stage. The most recent World Health Organization (WHO)
      classification of tumours of the urinary system includes urothelial flat lesions:
      flat hyperplasia, dysplasia and carcinoma in situ. The papillary lesions are
      broadly subdivided into benign (papilloma and inverted papilloma), papillary
      urothelial neoplasia of low malignant potential (PUNLMP) and non-invasive
      papillary carcinoma (low or high grade). The initial proposal of the 2004 WHO has
      been achieved, with most reports supporting that categories are better defined
      than in previous classifications. An additional important issue is that PUNLMP,
      the most controversial proposal of the WHO in 2004, has lower malignant behaviour
      than low-grade carcinoma. Whether PUNLMP remains a clinically useful category, or
      whether this category should be expanded to include all low-grade, stage Ta
      lesions (PUNLMP and low-grade papillary carcinoma) as a wider category of less
      aggressive tumours not labelled as cancer, needs to be discussed in the near
      future. This article summarizes the recent literature concerning important issues
      in the pathology and the clinical management of patients with bladder urothelial
      carcinoma. Emphasis is placed on clinical presentation, the significance of
      haematuria, macroscopic appearance (papillary, solid or mixed, single or
      multiple) and synchronous or metachronous presentation (field disease vs
      monoclonal disease with seeding), classification and microscopic variations of
      bladder cancer with clinical significance, TNM distribution and the pathological
      grading according to the 2004 WHO proposal.

PMID- 18815925
TI  - Hereditary bladder cancer.
AB  - First degree relatives of patients with bladder cancer have a two-fold increased
      risk of bladder cancer but high-risk bladder cancer families are extremely rare.
      There is no clear Mendelian inheritance pattern that can explain the increased
      familial risk. This makes classical linkage studies for the mapping of
      susceptibility genes impossible. The disease is probably caused by a combination
      of exposure to exogenous carcinogens and a large number of susceptibility genes
      with modest effects. Genome-wide association studies are better suited to
      identify these genes. Three such studies are currently underway and are expected
      to report their results in 2008.

PMID- 18815926
TI  - Bladder cancer subtypes defined by genomic alterations.
AB  - Bladder tumours comprise a heterogeneous group with respect to both
      histopathology and clinical behaviour. Although many features of bladder tumours
      have been studied, assessment of risk for recurrence and progression to invasive
      disease is not precise and response to specific therapies cannot be predicted
      accurately. It is anticipated that a thorough knowledge of the molecular
      alterations that are involved in the development and progression of bladder
      cancer will lead to greater predictive power and the application of novel
      individualized therapies. This review summarizes the current state of knowledge
      of genomic alterations found in transitional cell carcinoma and putative
      precursor lesions.

PMID- 18815927
TI  - Genetic epidemiology of bladder cancer: scaling up in the identification of low
      penetrance genetic markers of bladder cancer risk and progression.
AB  - Bladder cancer is an increasingly important international public health problem.
      As a multifactorial disease, both environmental and genetic factors are involved
      in its development and progression. This neoplasm is a paradigm for the
      participation of low-penetrance genetic variants (GSTM1-null and NAT2-slow) and
      provides the best established gene-environment interaction in cancer (NAT2-slow *
      tobacco). Genetic variants in nucleotide excision and double strand break DNA
      repair pathways have provided promising results, ERCC2-XPD rs238406 being the
      most consistent variant associated with an increased of bladder cancer risk, by
      itself and by interacting with tobacco. Variants in other pathways such as cell
      cycle control, 1-C metabolism and inflammation have been studied, although the
      results are inconsistent. Three very large whole genome association studies are
      being undertaken using the same genotyping platform. Their results will be
      available soon. Genetic variants have seldom been considered as markers of
      prognosis or response to therapy in this tumour. The results of these studies are
      inconclusive. Other issues that need to be addressed are the role of genetic
      variants in different population subgroups--defined by ethnicity, gender and age,
      among others--and the association with bladder cancer subphenotypes according to
      clinical, pathological and molecular characteristics of the tumour. This
      endeavour can only be achieved by integrating multidisciplinary tools and
      information. Can this information be applied better to identify high-risk
      populations? Can the information be used to better assess prognosis or predict
      response to therapy? These questions require large, well-designed, multicentre
      studies to be conducted. Funding agencies should be aware of these needs.

PMID- 18815928
TI  - Tissue microarray studies in bladder cancer.
AB  - The introduction of tissue microarray (TMA) methodology 10 years ago has provided
      a valuable tool for high-throughput genomic and proteomic analyses. Using this
      method hundreds of minute tissue samples can be investigated on one microscopic
      glass slide. Several studies demonstrated that these small tissue areas are
      representative for the entire tumour block and can provide reliable information
      on the relation of molecular markers and clinical outcome of the patient. Types
      of TMA used in bladder cancer research include defined clinical case series,
      stage-specific series (e.g. pT1), stage progression series, TMAs containing all
      specimens from clinical trials for specific therapies, flat (pre)neoplastic
      lesions, cell culture pellets and mouse model TMAs. The TMA technique has
      frequently been used in bladder cancer research to evaluate immunohistochemical
      candidate markers for prognosis and to reveal the amplification frequency of
      candidate oncogenes in regions with copy number alterations detected by
      comparative genomic hybridization and array-based methods. In addition,
      multimarker expression studies of several specific biological functions (e.g.
      apoptosis or cell-cycle proteins) or signal transduction pathways have been
      performed. TMAs are also used for validation of array-based gene expression
      studies on the protein level. TMA technology represents a crucial technique for
      translating new information on molecular changes in bladder cancer into clinical
      practice.

PMID- 18815929
TI  - Detection of tumours of the urinary tract in voided urine.
AB  - Patients with non-muscle-invasive bladder cancer are treated by transurethral
      resection. About 60-70% of these patients will develop recurrences and in 11% of
      these cases progression to a muscle-invasive tumour occurs. Surveillance of
      patients by cystoscopy is therefore carried out every 3-4 months in the first 2
      years and yearly thereafter. Several biomarkers have been developed that
      potentially can detect recurrent bladder cancer in voided urine samples and may
      present an alternative for the invasive cystoscopy procedure. Recently, van Rhijn
      reviewed the performance of several of these biomarkers regarding detection of
      recurrent disease in patients under surveillance. In general, sensitivities were
      much lower when only patients under surveillance were taken into account than
      when the patient cohorts included patients with primary disease or patients with
      high-grade tumours. In this article recent new data on those markers that
      displayed a sensitivity and specificity of at least 70% as mentioned in the
      review by van Rhijn are reviewed. The literature selected was limited to those
      papers in which the performance of makers was assayed only on urine samples of
      patients under surveillance. The markers with sensitivity and specificity over
      70% that were selected from the previous study are Lewis X, NMP22, microsatellite
      analysis (MA), CYFRA 21.1, cytokeratin 20 and the UroVysion fluorescence in situ
      hybridization (FISH) test. Recent new developments such as the use of FGFR3
      mutation analysis and methylation detection are also discussed. In conclusion,
      tests such as the UroVysion FISH test and MA are able to detect most concomitant
      recurrences and to predict recurrent disease. In general, lesions that are missed
      are pTa and low grade. With MA several upper tract recurrences were identified
      that were missed by cystoscopy. The value of the most promising urine tests needs
      to be established in longitudinal studies and exclusively on patients under
      surveillance for recurrent disease. A longitudinal setting allows subsequent
      urine samples to be tested and this increases sensitivity because a negative test
      outcome sometimes occurs between positive ones. Stratification of patients
      according to the genetic status of their primary tumours and smoking habits
      should be investigated. Decision models should be developed that recommend at
      which points in time cystoscopy or urine testing should be performed.

PMID- 18815930
TI  - Molecular alterations associated with bladder cancer initiation and progression.
AB  - Bladder cancer is the fifth most commonly diagnosed non-cutaneous solid
      malignancy, and the second most commonly diagnosed genitourinary malignancy
      amongst people living in the United States, where it is estimated that more than
      61,000 new cases of bladder cancer will be diagnosed in the year 2008.
      Approximately 90% of malignant tumors arising in the urinary bladder are of
      epithelial origin, the majority being transitional cell carcinomas. Early stage
      bladder tumors have been classified into two groups with distinct behavior and
      unique molecular profiles: low grade tumors (always papillary and usually
      superficial), and high-grade tumors (either papillary or non-papillary, and often
      invasive). Clinically, superficial bladder tumors (stages Ta and Tis) account for
      75% to 85% of neoplasms, while the remaining 15% to 25% are invasive (T1, T2-T4)
      or metastatic lesions at the time of initial presentation. Studies from the
      author's group and others have revealed that distinct genotypic and phenotypic
      patterns are associated with early versus late stages of bladder cancer. Most
      importantly, early superficial diseases appear to segregate into two main
      pathways. Superficial papillary bladder tumors are characterized by gain-of
      function mutations, mainly affecting classical oncogenes such as RAS and FGFR3.
      Deletions of chromosome 9, mainly allelic losses on the long arm (9q) are also
      frequent events in these tumors. Such genetic alterations are observed in most if
      not all superficial papillary non-invasive tumors (Ta), but only in a small
      subset of invasive bladder neoplasms. Flat carcinoma in situ (Tis) and invasive
      tumors are characterized by loss-of-function mutations, affecting the prototype
      tumor suppressor genes, including p53, RB and PTEN. These alterations are absent
      or very rare in the Ta tumors analyzed, but have been frequently identified in
      invasive bladder carcinomas. Based on these data, a novel model for bladder tumor
      progression has been proposed in which two separate genetic pathways characterize
      the evolution of superficial bladder neoplasms. Numerous individual molecular
      markers have been identified in the tissue specimens that correlate to some
      extent with tumor stage, and possibly with prognosis in bladder cancer. However,
      these molecular prognosticators do not play a role in the clinical routine
      management of patients with bladder tumors, mainly due to lack of large
      prospective validation studies. Thus, the need for development of specific tissue
      and serum tumor markers for prognostic stratification remains. The advent of high
      throughput microarrays technologies allows comprehensive discovery of targets
      relevant in bladder cancer progression, which could be translated into new
      approaches for drug and biomarker development. Further investigation is warranted
      to define novel biomarkers specific for bladder cancer patients based on the
      molecular alterations of tumor progression, and multiplexed strategies for
      clinical management.

PMID- 18815931
TI  - Gene signatures for risk-adapted treatment of bladder cancer.
AB  - A major challenge for molecular diagnosis of bladder cancer is the subdivision of
      tumors beyond histological classifications into clinical relevant molecular
      subgroups. The evolution of molecular high-throughput techniques assessing a
      large number of molecular features at the same time has made comprehensive
      investigation of these subgroups possible. Molecular signatures for disease
      stage, grade, progression, carcinoma in situ, presence of metastases, and
      treatment response have been reported. Some of these molecular signatures are now
      being tested in multicenter studies with the purpose of introducing these into
      the clinic, for planning of follow-up and treatment selection. In this review, we
      define the clinical relevant subgroups and give an overview of recent advances in
      marker identification in the field of non-muscle invasive and invasive bladder
      cancer. Furthermore, we stress the methods and materials needed to translate such
      molecular profiles into clinically useful tests.

PMID- 18815932
TI  - How to combine the molecular profile with the clinicopathological profile of
      urothelial neoplastic lesions.
AB  - The current World Health Organization (WHO) 2004 classification of urothelial
      neoplasms was based on an attempt to reconcile molecular-genetic and pathology
      findings. This article provides an overview of the more recent molecular-genetic
      findings in the field and critically appraises their relationship with each of
      the WHO 2004 disease categories. Most of the WHO 2004 categories were
      successfully distinguished by means of expression and genome profiling and by
      distinct genetic alterations. Regarding urothelial papilloma, clinical and
      limited molecular-genetic data seem to suggest that they may not represent a
      precursor lesion for bladder cancer. It is more likely that urothelial papilloma
      is a benign neoplasm sharing mutations in the fibroblast growth factor-3 gene
      with seborrhoeic keratosis, allegedly its epidermal counterpart. Genetic
      alterations in papillary urothelial neoplasia of low malignant potential are
      identical to those found in non-invasive low-grade papillary urothelial
      carcinoma, implying that they are within a spectrum of the same neoplasm.
      Expression profiling data corroborate the view that (secondary) carcinoma in situ
      may act not only as a precursor lesion for invasive non-papillary urothelial
      carcinoma, but also as a precursor for non-muscle-invasive papillary urothelial
      carcinoma. Given the significant molecular genetic differences between non
      invasive and invasive papillary urothelial carcinomas and their analogy with
      exophytic neoplastic precursor lesions in other organ systems, an alternative
      nomenclature is proposed, replacing papillary urothelial carcinoma with papillary
      intraurothelial neoplasm for the non-invasive (pTa) papillary carcinomas.

PMID- 18815934
TI  - Screening for bladder cancer: theoretical and practical issues in considering the
      treated and untreated natural history of the various forms of the disease.
AB  - Screening is used to detect disease earlier in its course, allow earlier
      treatment, and presumably decrease morbidities and potential mortality associated
      with the later expression of more advanced disease and presumably more complex
      treatments consequently required. Judicious screening in bladder cancer depends
      on an understanding of how the different forms of bladder cancer express their
      biological potential, whether the tools available for screening have sufficient
      sensitivity and specificity to have accurate predictive value in accurately
      diagnosing and assessing each cancer diathesis earlier in its course, and how
      this may influence the morbidities and mortality associated with each. The
      principles of screening, potential biases that can affect their accuracy and the
      interpretation of outcomes, tools currently available for screening, their
      efficacies and pitfalls, and lessons learned from studies of the role of
      screening in prostate cancer will be reviewed to offer an understanding of the
      potential role that screening may play in the different forms of bladder cancer
      in the context of their preclinical and treated natural history.

PMID- 18815933
TI  - Combining a molecular profile with a clinical and pathological profile:
      biostatistical considerations.
AB  - The use of molecular markers and gene expression profiling provides a promising
      approach for improving the predictive accuracy of current prognostic indices for
      predicting which patients with non-muscle-invasive bladder cancer will progress
      to muscle-invasive disease. There are many statistical pitfalls in establishing
      the benefit of a multigene expression classifier during its development. First,
      there are issues related to the identification of the individual genes and the
      false discovery rate, the instability of the genes identified and their
      combination into a classifier. Secondly, the classifier should be validated,
      preferably on an independent data set, to show its reproducibility. Next, it is
      necessary to show that adding the classifier to an existing model based on the
      most important clinical and pathological factors improves the predictive accuracy
      of the model. This cannot be determined based on the classifier's hazard ratio or
      p-value in a multivariate model, but should be assessed based on an improvement
      in statistics such as the area under the curve and the concordance index.
      Finally, nomograms are superior to stage and risk group classifications for
      predicting outcome, but the model predicting the outcome must be well calibrated.
      It is important for investigators to be aware of these pitfalls in order to
      develop statistically valid classifiers that will truly improve our ability to
      predict a patient's risk of progression.

PMID- 18815935
TI  - Bladder cancer: chemoprevention, complementary approaches and budgetary
      considerations.
AB  - Bladder cancer results from complex and only partially understood host
      environmental interactions. Tobacco smoking is the greatest risk factor for
      bladder cancer, but the actual risk to an individual reflects not only the amount
      of exposure to the carcinogens in tobacco smoke but also host susceptibility to
      these carcinogens and possibly other factors. Lifestyle may have a significant
      effect on the incidence of this disease. The forms of chemoprevention and their
      relevance to bladder cancer, the impact of lifestyle and complementary medicine,
      and the costs of diagnosing and treating bladder cancer are reviewed to provide a
      base for advances in decreasing the incidence, recurrence and costs of this
      disease.

PMID- 18815936
TI  - Intratympanic administration of methylprednisolone reduces impact of experimental
      intensive impulse noise trauma on hearing.
AB  - CONCLUSION: The present findings demonstrated that intratympanic
      methylprednisolone (MP) reduces the impact of impulse noise trauma on hearing and
      in part preserves the hair cells from death 1 h after exposure to intensive
      impulse noise. OBJECTIVE: To examine the treatment efficiency of intratympanic MP
      (IT-MP) with different methods of administration on cochlear injury induced by
      exposure to intensive impulse noise. MATERIALS AND METHODS: Fifty-five guinea
      pigs were assigned into six groups and exposed to intensive impulse noise, i.e.
      60 impulses at 165 dB SPL peak pressure with 0.5 ms duration and 2 s intervals.
      The auditory brainstem response (ABR) was used to examine the hearing thresholds.
      Cochlear morphology was examined to estimate the inner and outer hair cell loss
      induced by impulse noise exposure. MP was applied as a rescue agent via different
      modalities of administration. RESULTS: The ABR threshold value of IT-MP1 or IT
      MP4 groups significantly decreased at 4 weeks as compared with the IT-NS (IT 0.9%
      physiological saline) group. The ABR threshold value of the group that received
      intramuscular administration of MP (IM-MP) also decreased at 4 weeks as compared
      with the IT-NS group. Significant hair cell loss was observed at the region 40
      50% from the apex in the present model. Within this region, the residual hair
      cell number in the IT-MP1 or IT-MP4 groups was significantly greater than that in
      the IT-NS group.

PMID- 18815937
TI  - Health-related quality of life (SF-36) during telemonitoring of home blood
      pressure in hypertensive patients: a randomized, controlled study.
AB  - Telemonitoring of home blood pressure (BP) is a new advance in home BP monitoring
      (HBPM) and has proved effective in improving BP control. The impact of
      telemedical HBPM on health-related quality of life (HRQOL) has not yet been
      studied. The purpose of this study is to compare HRQOL using a generic scale (SF
      36) in patients with antihypertensive treatment based on telemedical HBPM and in
      patients with antihypertensive treatment based on conventional monitoring of
      office BP. Hypertensive patients (n = 223) recruited by general practitioners
      participated in the study. In the intervention group, antihypertensive treatment
      was based on telemedical HBPM. In the control group, patients (n = 118) received
      usual care with office visits to monitor BP. After 6 months, participants filled
      out SF-36 questionnaires. Patients in the telemonitoring group (T) had higher
      mean scores in the bodily pain domain than patients in the control group (C),
      indicating less pain and interference with activities among telemonitored
      patients [T: 85.3(20.2), C: 78.3(26.4), p = 0.026)]. Patients were more likely to
      feel their general health had worsened during the last year if antihypertensive
      treatment was based on conventional office measurements. In the bodily pain
      domain and health transition scale, scores were slightly better among
      telemonitored patients compared with control patients.

PMID- 18815938
TI  - Management of cocaine-induced cardiac arrhythmias due to cardiac ion channel
      dysfunction.
AB  - Cocaine use is common in many areas of the world, particularly the United States
      and Western Europe. Toxicity following the use of cocaine is associated with a
      wide range of clinical features. In this review, we will focus on the cocaine
      associated cardiac arrhythmias and, in particular, some of the controversies in
      their etiology and management. Cocaine can produce arrhythmias either through the
      production of myocardial ischemia or as a direct result of ion channel
      alterations. Excessive catecholamines, combined with sodium and potassium channel
      blockades, give rise to a wide variety of supra-ventricular and ventricular
      rhythms. The animal and human evidence for ion channel dysfunction is reviewed,
      and the effects of catecholamines are followed from the cardiac action potential
      to the development of arrhythmias. Finally, theoretical constructs are combined
      with existing evidence to develop a rational treatment strategy for patients with
      cocaine-induced cardiac arrhythmias. In particular, we review the evidence
      concerning the controversies relating to the use of lidocaine in comparison with
      sodium bicarbonate, in terms of QRS prolongation secondary to sodium channel
      blockade.

PMID- 18815939
TI  - Patients' and relatives' experience of difficulties following severe traumatic
      brain injury: the sub-acute stage.
AB  - The present study aimed to (1) identify the difficulties most frequently reported
      by individuals with severe traumatic brain injury (TBI) at the time of discharge
      from a sub-acute rehabilitation brain injury unit as well as difficulties
      reported by their relatives, (2) compare patients' and relatives' reports of
      patient difficulties, and (3) explore the role of injury severity, disability and
      other factors on subjective experience of difficulties. The primary measure was
      the European Brain Injury Questionnaire (EBIQ) administered to patients and to
      one of their close relatives at discharge. Results from 52 patients and 50
      relatives indicate that the most frequent complaints in both groups related to
      somatic and cognitive problems. Relatives reported significantly more
      difficulties than patients on all subscales of the EBIQ. However, the level of
      complaints in both patients and relatives was low compared to other studies using
      the EBIQ. Furthermore, the effects of injury severity and general level of
      functioning had limited impact on the subjective experience of difficulties.
      Implications of these findings, specifically as they pertain to the sub-acute
      stage are discussed.

PMID- 18815940
TI  - Identification and characterization of potential impurities of quetiapine
      fumarate.
AB  - Seven potential impurities, including by-products, starting materials and
      intermediates were identified in pharmaceutical substance quetiapine fumarate and
      characterized by spectroscopic methods (MS, IR, NMR). Based on these methods the
      structures of the impurities were assigned or confirmed as: impurity I: 2
      (phenylthio)aniline; impurity II: phenyl N-[2-(phenylthio)phenyl]carbamate;
      impurity III: N,N'-bis[2-(phenylthio) phenyl]urea; impurity IV: N-[2
      (phenylthio)phenyl]-1-piperazinecarboxamide hydrochloride; impurity V: N,N'
      bis[(2-phenylthio)phenyl]-1,4-piperazinedicarboxamide; impurity VI: 11-(1
      piperazinyl) dibenzo[b,f][1,4]thiazepine fumarate; impurity VII: 1,4
      bis(dibenzo[b,f][1,4] thiazepin-11-yl)piperazine. Structural elucidation of
      compounds, proposed MS fragmentation pathway and possible ways of formation of
      the impurities are also discussed.

PMID- 18815941
TI  - Prophylactic antibiotic treatment in acute necrotizing pancreatitis: East wind
      blows no good.

PMID- 18815942
TI  - Epigenetic silencing of LRRC3B in colorectal cancer.
AB  - OBJECTIVE: Tumor suppressor gene silencing via promoter hypermethylation is an
      important event in the pathogenesis of colorectal cancer (CRC). Some aberrant DNA
      hypermethylation has high tumor specificity, so it may contribute to early
      diagnosis of CRC. The objective of this study was to establish novel therapeutic
      and diagnostic strategies against CRC by identifying the novel methylation
      related genes. MATERIAL AND METHODS: Two microarray-based approaches were used to
      identify novel methylation-related genes in CRC. We identified methylation
      sensitive genes in colon cancer cell line SW1116 by comparing differential
      expression genes after treatment with the methylation inhibiting drug, 5-aza-2'
      deoxycytidine (5-aza-dC) using gene expression microarray. Promoter microarray
      analysis was performed to identify cancer-specific, methylation-related genes in
      two patients with CRC. Gene promoter methylation was identified by methylation
      specific polymerase chain reaction (PCR) (MSP) in primary CRC. Gene expression
      level was assessed using real-time PCR analysis. RESULTS: By using gene
      expression microarray, up-regulation of 253 genes was detected in the CRC cell
      line, SW1116, after treatment with 5-aza-dC. Of the 253 genes identified by gene
      expression microarray analysis, LRRC3B (leucine-rich repeat containing 3B) was
      isolated as a potential methylation-specific gene by promoter microarray
      analysis. MSP analysis showed frequent methylation of LRRC3B in primary CRC
      (24/31 cases, 77%). In addition, the LRRC3B methylation intensity was
      significantly higher in cancer tissues than in the corresponding non-cancerous
      tissues. Decreased LRRC3B expression (17/31, 55%) was observed in the cancer
      tissues by real-time PCR. CONCLUSIONS: LRRC3B may be a novel methylation
      sensitive tumor suppressor gene in CRC. LRRC3B methylation has significant tumor
      specificity and may be a biomarker of CRC.

PMID- 18815943
TI  - Behavioral regulation as a predictor of response to Children's Friendship
      Training in children with fetal alcohol spectrum disorders.
AB  - Children with fetal alcohol spectrum disorders (FASDs) evidence an array of
      structural brain abnormalities and neurocognitive deficits. Furthermore, previous
      research suggests that deficits in executive functioning (EF) may be associated
      with significant difficulties in the formation of positive peer relationships in
      this population. The purpose of the current study was to examine the role of EF
      as a predictor of treatment response to a controlled social skills intervention
      for children with FASDs. A total of 100 children between the ages of 6 and 12
      received Children's Friendship Training (CFT). Prior to treatment, parents
      completed the Behavior Rating Inventory of Executive Functioning (BRIEF).
      Treatment outcome was measured using parent report on the Social Skills Rating
      System (SSRS). The results demonstrated that behavioral regulation as measured on
      the BRIEF predicted the effectiveness of CFT for children with FASDs, regardless
      of general intellectual functioning. Specifically, the ability to control
      impulses, solve problems flexibly, and monitor emotional responses significantly
      predicted improvement in social skills and reduction in problem behaviors
      following CFT.

PMID- 18815944
TI  - How states of mind change in psychotherapy: an intensive case analysis of Lisa's
      case using the Grid of Problematic States.
AB  - This study uses the Grid of Problematic States (GPS) to examine Lisa's case, one
      of the most successful in the York Psychotherapy Depression Project. This study
      tried to assess whether the contents of mental experience form stable clusters
      consistent with a diagnosis of depression. It was possible with the GPS to
      pinpoint problematic states typical of depression and trace the transitional
      states occurring in Lisa between two different mental states: depressive and well
      being. The GPS analysis suggested that the treatment successfully managed to deal
      with symptoms and to change the patient's thought themes and emotions. At the end
      of treatment, Lisa was less sad and displayed some anger, and a state of being
      nurtured emerged.

PMID- 18815945
TI  - The case of Lisa and the assimilation model: the interrelatedness of problematic
      voices.
AB  - This study examines Lisa, a successful case of emotion-focused therapy, using the
      assimilation model as a lens to view and understand her changes. The assimilation
      model construes problems as voices, or parts of the self, that are unwanted and
      kept separate from other voices in the community that constitute the self.
      Progress in therapy, then, is construed as increasing the assimilation or
      integration of problematic voices into the community. Lisa made significant
      progress assimilating two distinct but related voices, described as movement
      through the Assimilation of Problematic Experiences Sequence. In the course of
      the analysis, the case of Lisa also informed the assimilation model by raising
      issues concerning the interrelatedness of problems and the dynamic nature of
      assimilation in the context of a multivoiced self.

PMID- 18815946
TI  - "You were always on my mind": therapists' intersession experiences in relation to
      their therapeutic practice, professional characteristics, and quality of life.
AB  - The experience of "being held in the mind of another" is a powerful metaphor for
      any relationship and is particularly pertinent to the therapist-patient bond.
      This study explores the frequency of therapists' thoughts and feelings about
      their patients between sessions (intersession experiences) and the relation of
      these to therapists' professional and demographic characteristics, difficulties
      experienced and coping strategies used in practice, and personal quality of life.
      Therapists (N=1,040) from the United States, Canada, and New Zealand completed
      the Therapist Intersession Experience Scale included in a survey with the
      Development of Psychotherapists Common Core Questionnaire (Orlinsky & Ronnestad,
      2005). Controlling for nationality, analyses showed that frequency of
      intersession experiences was associated most strongly with therapists' general
      level of difficulties in practice (10.3% of variance), use of constructive coping
      strategies (3.4%), and a few professional characteristics (3.9% combined).
      Implications of these findings for clinical theory and practice are discussed.

PMID- 18815947
TI  - Analysis of the therapist's verbal behavior during cognitive restructuring
      debates: a case study.
AB  - This paper reports a case study in which the authors analyze the application of
      the debate technique in cognitive restructuring so as to obtain a deeper
      understanding of the relevant behavioral processes. The authors examined the
      recordings of a clinical case of low mood disorder and selected five debates that
      dealt with the same problem. After their transcription, the authors analyzed the
      client-therapist verbal interaction. Results show changes in the verbalizations
      of both parties as the treatment progresses. The authors propose a new
      explanation of these changes, constituting a step forward in the theoretical
      explanation of the debate technique within the cognitive-behavioral approach.

PMID- 18815948
TI  - Beyond the individual: group effects in mindfulness-based stress reduction.
AB  - The authors explored the group as a source of change in mindfulness-based stress
      reduction (MBSR). Participants consisted of 606 adults in 59 groups who completed
      an 8-week MBSR program. The authors examined change in the General Symptom Index
      (GSI) of the Symptom Checklist-90-Revised and the Medical Symptom Checklist (MSC)
      from pre- to postintervention. Multilevel models were used to examine the extent
      to which groups differed in the amount of change reported by the participants.
      After controlling for pretreatment severity, group accounted for 7% of the
      variability in the GSI and 0% in the MSC. The authors discuss the implications of
      these findings for the practice of MBSR as well as for research investigating the
      effects of MBSR and other programs or psychotherapies.

PMID- 18815949
TI  - How do intake clinicians use patient characteristics to select treatment for
      patients with personality disorders?
AB  - Treatment selection in clinical practice is a poorly understood, often largely
      implicit decision process, perhaps especially for patients with personality
      disorders. This study, therefore, investigated how intake clinicians use
      information about patient characteristics to select psychotherapeutic treatment
      for patients with personality disorder. A structured interview with a forced
      choice format was administered to 27 experienced intake clinicians working in
      five specialist mental health care institutes in the Netherlands. Substantial
      consensus was evident among intake clinicians. The results revealed that none of
      the presented patient characteristics were deemed relevant for the selection of
      the suitable treatment setting. The appropriate duration and intensity are
      selected using severity or personal strength variables. The theoretical
      orientation is selected using personal strength variables.

PMID- 18815950
TI  - The narrative reconstruction of psychotherapy and psychological health.
AB  - When people complete psychotherapy, they carry the story of the experience with
      them. This retrospective reconstruction serves several psychological purposes,
      including contributing to narrative identity and influencing the maintenance of
      therapeutic gains after termination. Based on a prior qualitative investigation
      of therapy narratives (Adler & McAdams, 2007a), a new sample of 104 former
      clients wrote about their psychotherapy after treatment end. Quantitative
      analyses indicated that the retrospective narratives of participants high in
      subjective well-being focused on the protagonist's agency in struggling with a
      discrete problem. In addition, the narratives of participants high in ego
      development described a coherent story of growth. These findings suggest that the
      stories clients construct about psychotherapy reliably vary depending on their
      psychological health.

PMID- 18815951
TI  - Alliance ruptures and rupture resolution in cognitive-behavior therapy: a
      preliminary task analysis.
AB  - An initial ideal, rational model of alliance rupture and rupture resolution
      provided by cognitive-behavioral therapy (CBT) experts was assessed and compared
      with empirical observations of ruptures and their resolution in two cases of
      successful CBT. The initial rational model emphasized nondefensive acknowledgment
      and exploration of the rupture. Results indicated differences between what
      therapists think they should do to resolve ruptures and what they actually do and
      suggested that the rational model should be expanded to emphasize client
      validation and empowerment. Therapists' ability to attend to ruptures emerged as
      an important clinical skill.

PMID- 18815952
TI  - An intensive case analysis of client metacognition in a good-outcome
      psychotherapy: Lisa's case.
AB  - The authors analyzed the successful case of Lisa, a client with major depression,
      using the Metacognitive Assessment Scale (MAS). Consistently with the literature
      on depression, the authors hypothesize that Lisa's ability to reflect on mental
      states--here metacognition--is marginally affected. The authors found that Lisa
      was better at describing her own mind rather than understanding the mind of the
      others. Furthermore, the most severe impairment was in using metacognition to
      cope with mental state source of distress and to enact strategies to solve
      interpersonal problems. During the therapy such difficulties improved
      progressively. Limitations and implications of these findings are discussed.

PMID- 18815953
TI  - Patient interpersonal factors and the therapeutic alliance in two treatments for
      bulimia nervosa.
AB  - Although the therapeutic alliance is robustly associated with psychotherapy
      outcomes, less is known about factors that influence its development. This study
      examined the association between baseline patient interpersonal factors and
      patient-rated alliance in a randomized trial comparing cognitive-behavioral
      therapy (CBT) and interpersonal therapy (IPT) for bulimia nervosa. Using
      hierarchical linear modeling, early and middle alliance were negatively
      associated with interpersonal distress and positively associated with
      interpersonal affiliation. Middle alliance was also related to treatment group
      interactions with rigidity, affiliation, and control. Overall, alliance growth
      was higher in IPT than CBT. Using group-based trajectory analysis, three
      divergent alliance trajectories emerged (high and improving, low and improving,
      and low and stable), with group mean differences between two of them in terms of
      interpersonal distress and hostile-submissiveness.

PMID- 18815954
TI  - Attachment disorganization and borderline patients' metacognitive responses to
      therapists' expressed understanding of their states of mind: A pilot study.
AB  - This study explores the relationship between psychotherapists' validation
      interventions and patients' metacognitive responses at the beginning of treatment
      of borderline personality disorder (BPD). A model of BPD based on disorganized
      attachment provides the hypothesis that, before patients' internal working model
      of attachment has been corrected within the therapeutic relationship, therapist
      interventions that are likely to activate patients' attachment system are also
      likely to induce temporary disorganization of patients' metacognitive functions.
      Any validation intervention implies that therapists openly display an
      understanding and accepting attitude when they comment on patients' reported
      experiences and is, therefore, likely to activate the patients' attachment
      system. Linehan's (1993) manual of dialectic-behavioral therapy (DBT) was used as
      a guideline to assess validation interventions adopted by therapists. The
      transcripts of the second individual session in the psychotherapy of 19
      consecutive patients were analyzed. Checklists based on the DBT manual were used
      to identify therapists' validating, supportive, and neutral interventions. The
      Metacognitive Assessment Scale was used to assess changes in specific aspects of
      patients' metacognitive processes during therapeutic dialogues. Following
      validation interventions, patients' responses revealed significantly higher rates
      of temporary metacognitive failure in comparison to the responses solicited by
      neutral intervention.

PMID- 18815955
TI  - Comparison study of full and subthreshold bulimia nervosa: Personality, clinical
      characteristics, and short-term response to therapy.
AB  - This study compared symptomatological and personality differences between
      individuals with threshold bulimia nervosa (BN; n=39) and those with subthreshold
      BN (n=39) and their short-term response to a brief outpatient intervention.
      Participants were matched using a pairwise matching procedure, taking into
      account age, age of onset, and duration of the disorder. Both groups received the
      same brief outpatient psychoeducational therapy. The same assessment measures
      were used before and after treatment. With the exception of some clinical and
      psychopathological symptoms (higher depression and phobic anxiety in threshold
      BN), there were no significant between-group differences on scales of general
      psychopathology or personality traits. At the end of treatment, there were no
      significant between-group differences on abstinence rates for binge eating and
      vomiting, number of sessions attended, or dropout rates. Threshold BN and
      subthreshold BN share common psychopathological symptoms and personality traits.
      No differences in therapy outcome were observed for the two groups after a brief
      group psychoeducational intervention.

PMID- 18815956
TI  - What's on the therapist's mind? A grounded theory analysis of family therapist
      reflections during individual therapy sessions.
AB  - The authors used a videotape-assisted recall procedure to study the content of
      family therapists' inner conversations during individual sessions with a
      standardized client. Grounded theory was used to analyze therapists' reflections,
      resulting in a taxonomy of 282 different codes in a hierarchical tree structure
      of six levels, organized into four general domains: attending to client process;
      processing the client's story; focusing on therapists' own experience; and
      managing the therapeutic process. In addition to providing a descriptive model of
      therapists' inner conversation, this research led to an appreciation of the
      wealth of therapists' inner conversation. In particular, the authors found that
      therapists work hard to create an intersubjective space within which to talk by
      trying to be in tune with their clients and by using clients as a guide.

PMID- 18815957
TI  - A qualitative and quantitative study of psychotherapists' congruence in
      Singapore.
AB  - This study explores the phenomenological world of 11 Satir-based Singaporean
      Chinese therapists with regard to their experience of congruence. A mixed
      qualitative-cum-quantitative research method was used in this study. A
      phenomenological methodology was used to explore (a) the phenomenological world
      of therapists with regard to their lived experience of congruence in their
      personal or inner lives, (b) how this congruence is used in psychotherapy, and
      (c) how therapists can enhance their level of congruence. Quantitative findings
      include (a) significant nonparametric correlations among the intrapersonal,
      interpersonal, and transpersonal levels of congruence with overall congruence;
      (b) significant nonparametric correlation between intrapersonal congruence and
      interpersonal congruence; (c) significant nonparametric correlations between
      overall congruence and interpersonal congruence with self-esteem and life
      satisfaction; and (d) significant nonparametric correlations between
      intrapersonal congruence and self-esteem. These results may have research and
      clinical implications for the practice of psychotherapy.

PMID- 18815958
TI  - Responding mindfully to distressing psychosis: A grounded theory analysis.
AB  - This study investigates the psychological process involved when people with
      current distressing psychosis learned to respond mindfully to unpleasant
      psychotic sensations (voices, thoughts, and images). Sixteen participants were
      interviewed on completion of a mindfulness group program. Grounded theory
      methodology was used to generate a theory of the core psychological process using
      a systematically applied set of methods linking analysis with data collection.
      The theory inducted describes the experience of relating differently to psychosis
      through a three-stage process: centering in awareness of psychosis; allowing
      voices, thoughts, and images to come and go without reacting or struggle; and
      reclaiming power through acceptance of psychosis and the self. The conceptual and
      clinical applications of the theory and its limits are discussed.

PMID- 18815959
TI  - New prospects for process research in group therapy: Text-based process variables
      in psychotherapeutic Internet chat groups.
AB  - This study focuses on the operationalization and validation of text-based process
      variables in psychotherapeutic Internet chat groups. The process variables
      activity, outdegree (OD; i.e., the frequency at which a group member addresses
      others in the group), and indegree (ID; i.e., the frequency at which a group
      member's name is mentioned by other group members or by the therapist [IDT]) were
      operationalized. Using 1,046 session transcripts from 130 participants of an
      Internet chat aftercare program, the authors studied the concurrent and
      predictive validity of activity, OD, ID, and IDT and of 52 text-based variables
      comprising linguistic, emotional, and cognitive aspects. Results showed
      consistent correlations between psychometric group ratings and the text-based
      variables ID, OD, and activity. The predictive validity of the variables IDT, ID,
      and activity was rather low but as good as the predictive validity of the
      psychometric ratings. The clinical implications of the results are discussed.

PMID- 18815960
TI  - Generating nonnegative attitudes among parents of depressed adolescents: The
      power of empathy, concern, and positive regard.
AB  - Parental negativity is associated with the onset and maintenance of adolescent
      depression. Reducing parental negativity is a primary focus of family-based
      treatments for this clinical population. This study examined the association
      between therapist relationship-facilitating and attachment-oriented interventions
      and the valence (i.e., positivity-negativity) of parents' attitudes toward their
      depressed adolescent in a sample of 13 sessions of attachment-based family
      therapy. Lag sequential analyses revealed that in good alliance sessions
      relationship-facilitating interventions, such as empathy and positive regard for
      the parent, were associated with parents' nonnegative attitudes toward their
      adolescent in the five speech turns subsequent to the intervention. Attachment
      oriented interventions, such as relational reframes, addressing core relational
      themes, and highlighting vulnerable emotions, were also intermittently associated
      with nonnegative parental attitudes in good alliance sessions. No such effects
      were evident for the comparison interventions. This study represents a first step
      in the process of testing specific strategies for reducing parental negativity in
      family therapy.

PMID- 18815961
TI  - Child and adolescent psychotherapy research: Introduction to the special section.

PMID- 18815962
TI  - Direct comparisons of treatment modalities for youth disorders: a meta-analysis.
AB  - A meta-analysis was conducted to determine whether differences in efficacy exist
      among treatment approaches applied to youth. Included were all studies published
      between 1980 and 2005 involving participants 18 years of age or younger with
      diagnoses of depression, anxiety, conduct disorder, and attention
      deficit/hyperactivity disorder that contained direct comparisons among two or
      more treatment methods intended to be therapeutic. Effect sizes were found to
      vary significantly, providing some evidence that differences in efficacy exist
      among treatments for these disorders in youth. However, the upper bound of the
      true difference in effects among treatments was small. Furthermore, researcher
      allegiance was found to be strongly associated with the difference in effect
      sizes so that when allegiance was controlled there was no evidence of any
      differences among treatments.

PMID- 18815963
TI  - First-session pathways to the working alliance in cognitive-behavioral therapy
      for adolescent depression.
AB  - In the current study of cognitive-behavioral therapy for 54 depressed
      adolescents, chained p-technique was applied to 14 therapist behaviors that were
      rated in each 10-min segment of Session 1 provided by eight female therapists.
      Four underlying factors were identified: experiential socialization, therapist
      responsiveness, therapist lapse, and remoralization. Analysis of changes in the
      prominence of these factors revealed significant Factor X Session Segment trends.
      Therapist responsiveness and remoralization growth curves across Session
      [corrected] accounted for significant variance in Session 4 [corrected] therapist
      rated alliance. Experiential socialization growth curves across Session 1 also
      accounted for significant variance in Session 3 adolescent-rated alliance.
      Results are discussed in terms of the importance of Session 1 therapist behaviors
      for adolescent alliance formation.

PMID- 18815964
TI  - Relationship of differentiation of self to adult clients' perceptions of the
      alliance in brief family therapy.
AB  - The authors examined differentiation of self, a multidimensional construct in
      Murray Bowen's (1976, 1978) family systems theory, as a predictor of clients'
      perceptions of the therapeutic alliance. Adult clients (N=38) in brief family
      therapy completed the Differentiation of Self Inventory-Revised (Skowron &
      Schmitt, 2003) during prescreening and the self-report version of the System for
      Observing Family Therapy Alliances (Friedlander & Escudero, 2002) after Session
      3. More differentiated adults reported significantly more positive overall
      alliances. In a canonical correlation analysis, four roots were extracted that
      together accounted for 56% of the shared variance. Interpretation of the single
      significant canonical root suggested that clients reporting less emotional
      reactivity were more likely to have strong feelings of safety in the family
      therapy context.

PMID- 18815965
TI  - The Bielefeld attachment questionnaires: overview and empirical results of an
      alternative approach to assess attachment.
AB  - The Bielefeld Client Expectations Questionnaire and the Bielefeld Partnership
      Expectations Questionnaire are two parallel German language self-report tools of
      adult attachment. The Bielefeld questionnaires are different from others in two
      important ways: (a) Attachment patterns are operationalized as configurations of
      scale scores, which allow qualitative distinctions in terms of functioning; and
      (b) five empirically identified attachment patterns are distinguished. A
      partially-secure pattern is described for the first time. Both instruments yield
      good psychometric properties, and the current results support their validity. The
      aim of the present article is to inform an international audience about an
      original approach for assessing attachment and to encourage its adaptation and
      standardization in other languages.

PMID- 18815966
TI  - Pretreatment clinical and psychosocial predictors of remission from depression
      after short-term psychodynamic psychotherapy and solution-focused therapy: a 1
      year follow-up study.
AB  - The mutual importance of different predictors of remission was studied in 163
      outpatients with depression receiving either short-term psychodynamic
      psychotherapy or solution-focused therapy. After a 1-year follow-up, the
      percentage of remission significantly varied between sociodemographic subgroups
      and was dependent on severity of symptoms, personality disorder, and psychosocial
      factors but not on psychiatric history, previous psychiatric treatment, or type
      of therapy received. Simultaneous study showed that the most significant
      predictors were sense of coherence (based on Sense of Coherence Scale [SOCS]),
      symptom severity (based on Symptom Checklist-90 [SCL-90] Global Severity Index
      [GSI]), and education. The relative risks of remission between the lowest and
      highest quartiles of SOCS and SCL-90 GSI were 0.06 and 0.22 (95% confidence
      intervals = 0.01-0.35 and 0.05-0.97), respectively. In conclusion, several
      background factors, especially sense of coherence, predict remission.

PMID- 18815967
TI  - Do you see what I see? A study about the interrater reliability in art therapy.
AB  - There are many clinical reports on art therapy, but there are few data from
      experimental research. The main goal of this study was to investigate the
      interrater agreement of 86 raters who evaluated a picture created during an art
      therapy session. This rating was based on formal (color, lines, shapes) and
      contextual criteria. The resulting interrater agreement was not satisfying
      (intraclass correlation coefficient = 0.18-0.52). The authors also address the
      question of whether raters are able to determine which picture was created at the
      beginning of the art therapy and which was created at the end. On the basis of
      the examination of five sets of pictures, it became apparent that they were not
      able to do so.

PMID- 18815968
TI  - Characteristics of effective psychological treatments of depression: a
      metaregression analysis.
AB  - Although many meta-analyses have shown that psychological therapies are effective
      in the treatment of depression, no comprehensive metaregression analysis has been
      conducted to examine which characteristics of the intervention, target
      population, and study design are related to the effects. The authors conducted
      such a metaregression analysis with 83 studies (135 comparisons) in which a
      psychological treatment was compared with a control condition. The mean effect
      size of all comparisons was 0.69 (95% confidence interval = 0.60-0.79). In
      multivariate analyses, several variables were significant: Studies using problem
      solving interventions and those aimed at women with postpartum depression or
      specific populations had higher effect sizes, whereas studies with students as
      therapists, those in which participants were recruited from clinical populations
      and through systematic screening, and those using care-as-usual or placebo
      control groups had lower effect sizes.

PMID- 18815969
TI  - Resonating minds: a school-independent theoretical conception and its empirical
      application to psychotherapeutic processes.
AB  - The resonating minds theory will be introduced as a means to describe
      psychotherapeutic processes and change. It builds on the mind-brain interface
      with psychotherapeutic interventions causing change in the brain, an altered
      brain causes changes in the emotional, cognitive, and behavioral regulation, and
      this again will change the types of subsequent therapeutic interventions. For the
      empirical assessment of this theory the therapeutic cycles model will be used. It
      is based on computer assisted analysis of verbatim transcripts using emotional
      tone, abstraction and narrative style as language measures. Sample applications
      and studies are shortly presented in order to provide evidence for the
      applicability and face validity of this approach.

PMID- 18815970
TI  - Underutilization of short-term group therapy: enigmatic or understandable?
AB  - Given the evidence for the efficacy, applicability, and efficiency of the group
      therapies, they appear to be underutilized by clinicians, therapists, and
      researchers. This article considers reasons for their underutilization. The
      article also considers procedures for lessening patient and therapist tendencies
      to resist participating in the group therapies relative to individual therapies.
      Underutilization not only deprives patients of effective treatment for a wide
      range of problems but deprives therapists from experiencing fascinating and
      rewarding therapeutic processes. That has been the experience of the author after
      more than 35 years of conducting and studying group therapies.

PMID- 18815971
TI  - A psychotherapy researcher's perspective on therapist self-awareness and self
      focused attention after a decade of research.
AB  - In this Early Career Award paper, the interplay between quantitative and
      qualitative approaches to self-awareness in the psychotherapy literature is
      described. In addition, the linkages between therapist self-awareness and self
      focused attention discussed in the cognitive and social psychology literatures
      are also addressed. Contradictory sets of findings are examined; for example,
      momentary states of therapist self-awareness have at times been associated with
      anxiety or poor performance and at other times with positive interpersonal
      processes and client perceptions. Some of the studies on the management of
      distracting self-awareness are also reviewed, and suggestions for future research
      in the areas of mindfulness, attentional flexibility, and the person of the
      therapist are provided.

PMID- 18815972
TI  - Avoidance motivation in psychological problems and psychotherapy.
AB  - Avoidance of aversive experiences is common to all human beings. However, when
      avoidance is too strong, it might be associated with impaired psychological
      functioning and psychopathology. This article examines the role of avoidance
      motivation in psychological problems and psychotherapy from conceptual,
      assessment, and empirical perspectives. The concept of avoidance motivation is
      introduced, and measures of the intensity and satisfaction of avoidance
      motivation that the author developed are presented. Empirical findings generated
      using these measures are also reported. The findings address the role of
      avoidance motivation in relation to well-being, psychological problems, and
      psychotherapy outcome. The theoretical and practical implications of these
      findings are discussed and avenues for further research explored.

PMID- 18815973
TI  - Helping alliance and outcome in psychotherapy: what predicts what in routine
      outpatient treatment?
AB  - This naturalistic longitudinal study analyzed the reciprocal dependency of the
      helping alliance and symptom outcome over the course of mid- and long-term
      outpatient psychotherapy as practiced in routine care in Germany. Patient-rated
      helping alliance and symptom distress were assessed repeatedly over a 2-year
      period in a sample of 259 outpatients in psychodynamic, cognitive-behavioral, and
      psychoanalytic psychotherapy. Hierarchical linear models showed that initial
      symptom distress negatively predicted subsequent quality of the helping alliance
      but not vice versa. Only initial symptom distress affected symptom status at the
      last treatment session. These results raise doubts about the helping alliance
      being a strong predictor of outcome and indicate that other patient and therapist
      variables might be more important for treatment success.

PMID- 18815974
TI  - Case studies of the attainment of insight in dream sessions: replication and
      extension.
AB  - To replicate and extend the Hill, Knox, et al. (2007) case study of a client who
      attained insight in one session of dream work, the authors examined two
      additional single-session cases: one in which a client gained insight and another
      in which a client did not. The observations across all three cases suggest that
      the two clients who acquired insight had positive attitudes toward dreams; were
      motivated and involved in session; and were nonresistant, trusting, and
      affectively present but not overwhelmed. The client who did not gain insight
      questioned the value of dreams and was resistant, untrusting, and emotionally
      overwhelmed. Therapist adherence and competence using the dream model, ability to
      manage countertransference, and effective use of probes for insight distinguished
      the therapists whose clients gained insight from the therapist whose client did
      not.

PMID- 18815976
TI  - Research on client experiences of therapy: introduction to the special section.

PMID- 18815977
TI  - Clients' experiences of moments of sadness in psychotherapy: a grounded theory
      analysis.
AB  - Although few studies have examined the experience of depression, no research has
      been conducted on the experience of sadness in psychotherapy. In this study,
      clients were interviewed about their experience of sadness using an interpersonal
      process recall method, these interviews were subjected to grounded theory
      analysis, and a model of sadness experienced in psychotherapy was derived. The
      resulting core category--in therapy, the experience of sadness is a struggle
      against the fear of becoming trapped within the painful, existential question
      "Who am I?"--captures the essence of the experience of the clients' sadness and
      describes the struggle, the causes of sadness, and ways therapists facilitated
      sadness exploration. The findings are discussed in reference to clinical
      application and future psychotherapy research.

PMID- 18815978
TI  - Clients' experiences of difference with therapists: sustaining faith in
      psychotherapy.
AB  - Informed by the research literatures on values and multiculturalism, this study
      was designed to investigate clients' experiences of difference with therapists.
      Using a qualitative method--grounded theory--a model was developed to capture the
      essence of these experiences of difference. Five clusters highlight the client
      processes of being vigilant for differences, feeling threatened by differences,
      minimizing differences and focusing on positive relational factors, discussing
      differences, and beneficial personal growth resulting from differences. The core
      category describes the importance of clients maintaining faith in themselves, the
      therapist, and the therapeutic technique as differences are negotiated.
      Contributions and implications for practice and research on issues of managing
      values, multicultural differences, and transference are discussed.

PMID- 18815979
TI  - Participants' perspectives on cognitive-behavioral therapy for adherence and
      depression in HIV.
AB  - As part of the process of developing cognitive-behavioral therapy (CBT) for
      medical adherence and depression (Safren, Gonzalez, & Soroudi, 2007), the authors
      conducted exit interviews among 14 HIV-infected patients who received the
      intervention, and transcribed, coded, and analyzed these data. The authors
      concluded that CBT was structured yet flexible, developed self-awareness
      emphasized social support, and involved therapist empathy and supportiveness.
      Limitations included the discomfort of discussing personal information and the
      impact of feeling ill on attendance and homework completion. Suggestions included
      more sessions, more flexibility in scheduling appointments, and more realistic
      and clear expectations regarding homework. These results provide insights about
      strengths and limitations of this psychotherapy with medically ill patients and
      may help to maximize intervention effectiveness and client acceptability.

PMID- 18815980
TI  - Client experiences of helpful factors in a day treatment program: a qualitative
      approach.
AB  - The goal of the present study is to provide more information about which specific
      aspects of a day treatment program are experienced as most helpful by the
      patients. A semistructured interview was conducted. The narrated episodes were
      analyzed using a combination of grounded theory (Strauss & Corbin, 1997) and
      qualitative content analysis (Mayring, 2000). The authors collected 69 interviews
      of 26 patients over a 12-month period. The results show eight groups of helpful
      factors (the transfer factors being the most specific day clinical group) that
      are embedded in a conceptual frame of other categories. The discussion shows how
      they can be linked to other theoretical and empirical concepts, including the
      Assimilation of Problematic Experiences Scale (Stiles et al., 1990).

PMID- 18815981
TI  - Helpful and unhelpful therapy experiences of LGBT clients.
AB  - The purpose of this study was to identify a broad range of variables that
      characterize the helpful and unhelpful therapy experiences of lesbian, gay,
      bisexual, and transgender (LGBT) individuals. Interviews were completed with a
      diverse sample of 42 LGBT individuals who have been in therapy, and a content
      analysis was conducted. Results indicated that basic counseling skills and
      relationships were key determinants of the quality of LGBT clients' therapy
      experiences. Also important to the helpfulness of the therapy experience were
      therapist variables such as professional background and attitudes toward client
      sexual orientation/gender identity; client variables such as stage of identity
      development, health status, and social support; and environmental factors such as
      confidentiality of the therapy setting.

PMID- 18815982
TI  - Patients' experiences of self-disclosure in psychotherapy: the effects of gender
      and gender role identification.
AB  - This study examined the effects of gender and gender role identification on 223
      patients' experiences of self-disclosure in psychotherapy. Factor analysis of the
      Disclosure-to-Therapist Inventory-IV revealed two dimensions: a distress factor,
      reflecting the perceived difficulty and the anticipated impact of disclosures on
      the therapist, and an openness factor, reflecting the extent and perceived
      importance of disclosures and the interpersonal connection experienced during
      them. Female patients working with female therapists experienced greater distress
      in disclosure than male patients working with female therapists; in addition,
      patients with more flexible gender role identifications (i.e., androgynous)
      experienced greater openness than those with more traditional gender
      identifications. Findings suggest a need for greater discussion in therapy of the
      effects of gender on disclosure.

PMID- 18815983
TI  - Mental health characteristics of patients assigned to long-term ambulatory
      psychoanalytic psychotherapy and psychoanalysis in the Netherlands.
AB  - The present study investigated mental health characteristics of 170 patients
      assigned to long-term psychoanalytic psychotherapy (PP) versus psychoanalysis
      (PA) across treatment and studies. Both univariate and multivariate statistics
      showed that the main difference between treatments was found in the interpersonal
      domain. PA patients reported significantly more interpersonal problems (as
      measured by the Inventory for Interpersonal Problems-64), scored higher on the
      avoidant coping style and lower on the perceptual thinking index of the Rorschach
      Comprehensive System, and scored lower on Aggressiveness and Psychoticism
      Minnesota Multiphasic Personality Inventory-2 PSY-5 scales compared with PP
      patients. Compared with psychoanalytic patients in other studies, our patients
      had similar levels of mental health problems, although not always in the same
      health areas. Limitations of the study were noted, such as the lack of outcome
      data and other comparison groups.

PMID- 18815984
TI  - Tattoos, body piercings, and self-injury: is there a connection? Investigations
      on a core group of participants practicing body modification.
AB  - Reliable psychosocial data about practitioners of body piercing and tattooing are
      few and controversial. The goal of this study was to reinvestigate the issue by
      studying a large sample of individuals with body modifications (BMs), focusing on
      the motives and relations to biographical events. A 55-item anonymous self-report
      questionnaire was distributed among volunteers of what is considered to be a core
      group of individuals wearing BMs (N=432). Results show that BMs changed the
      participants' attitude toward their body considerably, and 34% of all
      participants reported BM practices in conjunction with decisive biographical
      events. Twenty-seven percent of the participants admitted self-cutting during
      childhood. This group differed from the group without self-cutting with respect
      to several features before, during, and after BM. The rate of medical
      complications of BM was 16% in the total sample, with a remarkably higher rate
      (26%) among participants with a history of self-cutting. The data suggest that
      the significance of BMs ranges from simple peer group imitations to highly
      informative symptoms of possibly severe psychopathological conditions. In the
      latter case, BMs sometimes serve as therapeutic substitutes.

PMID- 18815985
TI  - Assessing living skills in forensic mental health care with the behavioural
      status index: a European network study.
AB  - Assessment of living skills and violence risk in forensic psychiatric patients is
      a priority for clinicians. Suitably fine-grained instruments are rare. The goal
      of this study was to compare a norm-based psychometric assessment battery (the
      Behavioural Status [BEST] Index) with known valid instruments. Parallel cohort
      studies were undertaken in four European countries. Inpatients from 24 forensic
      psychiatric clinics were assessed three times using five instruments measuring
      living skills, psychological symptoms, aggression, and violence risk. Positive
      clinical changes were noted in insight, empathy, and some behaviors related to
      communication and living skills, with little change in violence risk, which was
      low to medium for most patients. Clinical congruence was observed between
      logically cognate items of the BEST Index and comparison instruments. Evidence
      for the scientific and clinical utility of the BEST Index as an effective tool
      for forensic psychiatric practice is discussed.

PMID- 18815986
TI  - Therapeutic factors and language patterns in group therapy application of
      computer-assisted text analysis to the examination of microprocesses in group
      therapy: preliminary findings.
AB  - The aim of this single-case-design study was to examine the relationships between
      therapeutic factors in group therapy and the language features of the group
      dialogue. Forty-two transcripts from a group treatment were investigated. Emotion
      abstraction patterns (EAPs) were identified for the group as a whole using
      computer-assisted text analysis, and therapeutic factors were rated by external
      judges using the Kiel Group Psychotherapy Process Scale. Significant positive
      relationships were found between insight and the EAP connecting and between
      catharsis and the EAP experiencing. Interpersonal learning-output, catharsis, and
      self-disclosure showed higher scores in connection with the therapeutic cycle,
      which, according to the therapeutic cycle model, represents a sequence of EAP
      related to a successful therapeutic process. The current findings show that the
      use of EAPs allows the identification of key moments in a group therapy process.

PMID- 18815987
TI  - Language and therapeutic change: a speech acts analysis.
AB  - Drawing on the speech acts theory, a linguistic pattern was identified that could
      be expected to be associated to therapeutic change, characterized by being
      uttered in the first person singular and present indicative, and by being self
      referential in its propositional content. The frequency of the pattern was
      examined among verbalizations defined as change moments in three therapies with
      different theoretical orientation. Results show that the majority of change
      moments have the specified pattern, and that this pattern is significantly more
      frequent in change moments than in random non-change-related verbalizations, and
      so, it does not pertain to therapeutic conversation in general. Implications are
      discussed concerning the possibility of using the linguistic pattern as an
      additional and complementary criterion in the identification of moments of change
      in the therapeutic process.

PMID- 18815989
TI  - Statistical analysis of group-administered intervention data: reanalysis of two
      randomized trials.
AB  - Group-administered interventions often create statistical dependencies, which, if
      ignored, increase the rate of Type I errors. The authors analyzed data from two
      randomized trials involving group interventions to document the impact of
      statistical dependency on tests of intervention effects and to provide estimates
      of statistical dependency. Intraclass correlations ranged from .02 to .12.
      Adjusting for dependencies increased p values for the tests of intervention
      effects. The increase in the p values depended on the magnitude of the
      statistical dependence and available degrees of freedom. Results suggest that the
      literature may overstate the efficacy of group interventions and imply that it
      will be important to study why groups create dependencies. The authors discuss
      how dependencies impact statistical power and how researchers can address this
      concern.

PMID- 18815990
TI  - An in-session exploration of ruptures in working alliance and their associations
      with clients' core conflictual relationship themes, alliance-related discourse,
      and clients' postsession evaluations.
AB  - This exploratory study examined (a) the relationship among the occurrence of
      ruptures in the working alliance, the emergence of client's core conflictual
      relationship themes (CCRT), and focus of discourse within therapeutic sessions
      and (b) the relationship between ruptures in the working alliance and client's
      postsession evaluations of session's smoothness and depth. The authors included
      151 sessions from five therapies conducted in a student counseling center.
      Sessions were content analyzed by independent raters, and a self-report
      questionnaire was given to clients after each session. Ruptures were positively
      related to the emergence of clients' CCRT during the session, but only when the
      therapist was addressed as the "other." Sessions with ruptures were characterized
      by heightened discussion of working alliance components and were evaluated as
      less smooth than sessions without ruptures. Findings are discussed, and the
      importance of ruptures in working alliance for therapeutic change is emphasized.

PMID- 18815991
TI  - Written emotional disclosure: a controlled study of the benefits of expressive
      writing homework in outpatient psychotherapy.
AB  - The current study investigated the extent to which outpatient psychotherapy
      clients benefited from Pennebaker's expressive writing protocol (Pennebaker &
      Beall, 1986) adapted for use as a homework intervention. Participants were
      randomly assigned to written emotional disclosure or writing control conditions.
      Pre- and postintervention outcome measures were collected for three consecutive
      therapy sessions. Clients in the written emotional disclosure group showed
      significantly greater reductions in anxiety and depressive symptoms as well as
      greater overall progress in psychotherapy in comparison to the writing control
      group. Results suggest that emotional disclosure writing homework, in conjunction
      with outpatient psychotherapy, facilitates therapeutic process and outcome.

PMID- 18815992
TI  - Predoctoral interns' nondisclosure in supervision.
AB  - In interviews with 14 counseling center predoctoral interns regarding a
      significant nondisclosure in supervision, eight interns reported good supervisory
      relationships and six indicated that they experienced problematic supervisory
      relationships. Nondisclosures for the interns in good supervisory relationships
      related to personal reactions to clients, whereas nondisclosures for interns in
      problematic supervisory relationships related to global dissatisfaction with the
      supervisory relationship. In both groups, interns mentioned concerns about
      evaluation and negative feelings as typical reasons for nondisclosure. Additional
      reasons for nondisclosure for interns in problematic supervision were power
      dynamics, inhibiting demographic or cultural variables, and the supervisor's
      theoretical orientation. Both groups described negative effects of nondisclosure
      on themselves and their relationships with clients. Interns in problematic
      supervision also reported that nondisclosures had negative effects on the
      supervisory relationship.

PMID- 18815993
TI  - Does habitual body avoidance and checking behavior influence the decrease of
      negative emotions during body exposure in eating disorders?
AB  - The aim of the present study was to assess whether habitual body avoidance and
      body-checking behavior influences the decrease of negative emotions during body
      exposure. Twenty-one eating-disordered female participants completed the Body
      Image Avoidance Questionnaire and the Body Checking Questionnaire. On another
      day, a 40-min body exposure session was conducted under standardized conditions.
      Every 10 min, negative emotions were assessed. It was shown that the extent of
      decrease in negative emotions during the body exposure session could be predicted
      by a lower degree of body checking. Results indicate that habitual checking
      behavior seems to negatively influence the effect of body exposure. Therefore, an
      adaptation of body exposure to patients with a higher degree of body-checking
      behavior might be promising.

PMID- 18815994
TI  - Treatment failure in psychotherapy: the pull of hostility.
AB  - Client-therapist interactions were studied in 14 positive-change (PC) and 14
      negative-change or nonchange (NC) therapies with the same therapists and similar
      clients. Aggregated structural analysis of social behavior (SASB) scores showed
      increasingly dissimilar interaction styles between client and therapist in NC
      therapies. First-lag transition analyses of SASB codings of Sessions 3, 12, and
      20 showed the following differences: Stable hostile complementarity characterized
      NC within and across sessions. Hostile complementarity was nevertheless
      relatively rare. Therapists met clients' invitations to hostile responses most
      frequently in nonhostile ways, yet they initiated more belittling and ignoring
      interactions with NC clients, pointing to the subtly hostile therapeutic climate
      created. Rejection of therapists' interventions predicted negative outcome most
      strongly and escalated with time. Clients' skepticism may make therapists
      vulnerable to feelings of inadequacy and, if not dealt with therapeutically, may
      easily release the therapists' own hostility.

PMID- 18815995
TI  - Short form of the revised Vanderbilt therapeutic alliance scale: development,
      reliability, and validity.
AB  - This study presents the development and psychometric properties of a five-item
      version of the revised Vanderbilt Therapeutic Alliance Scale (VTAS-R Short Form).
      A total of 255 alliance ratings, derived from therapy sessions from 86 cases of
      family therapy for substance-abusing adolescents, were used to generate two
      separate subsamples. The first subsample was used to develop the five-item form
      and the second subsample to estimate the measure's reliability and concurrent and
      predictive validity. The VTAS-R Short Form evidenced high internal consistency,
      was highly correlated with the full-length VTAS-R, and predicted treatment
      completion and adolescents' days of cannabis use at 3 months follow-up. The
      findings suggest that the VTAS-R Short Form is a reliable and valid alternative
      to the full-length form.

PMID- 18815996
TI  - Tumor patients in psychodynamic psychotherapy including daydreaming: can imagery
      enhance primary process and positive emotions?
AB  - This therapy process study investigates the use of guided affective imagery for
      tumor patients. The therapeutic access to tumor patients is generally described
      as complex and challenging because of a disturbed emotion regulation and a
      defensive focus on reality. After autologous blood stem cell transplantation, 29
      patients were treated with psychotherapy, including two daydreaming imagery
      sessions. Three text-analytical measures--Affective Dictionary Ulm, Regressive
      Imagery Dictionary, and Computerized Referential Activity for verbatim session
      transcripts--as well as the Quality of Life Questionnaire and the Karnofsky
      Performance Status were administered. Results show that guided affective imagery
      was able to enhance the psychotherapeutic process in tumor patients by activating
      the primary process, decreasing anxiety, and increasing referential activity. The
      positive emotional shift during imagery was achieved by the patients irrespective
      of their oncological severity status. Study limitations and future directions for
      research are discussed.

PMID- 18815997
TI  - Randomized control trial of an integrated therapy for comorbid anger and
      gambling.
AB  - This study evaluated an integrated treatment for comorbid problem gambling,
      anger, and substance use. Problem gamblers with comorbid anger problems (N=42),
      half of whom also had substance use disorders, were randomized to either a 14
      week integrated treatment targeting anger and addictions (i.e., both gambling and
      substance use) or a specialized treatment-as-usual (TAU) for gambling and
      substance use. Participants were assessed at baseline (Tl), 14 weeks (T2), and 12
      weeks follow-up (T3). Relative to the TAU, participants in the integrated anger
      and addictions treatment reported significantly less gambling at T2 and T3 and
      less trait anger and substance use at T3. Findings suggest that it is important
      to screen gambling clients for the presence of comorbid anger and substance use
      problems and that, when present, these problems need to be addressed concurrently
      in gambling treatment in order to optimize treatment outcomes.

PMID- 18815998
TI  - States of minds in narcissistic personality disorder: three psychotherapies
      analyzed using the grid of problematic states.
AB  - The subjective experience of patients suffering from narcissistic personality
      disorder (NPD) has been studied using various methods. However, there has not
      been an analysis of psychotherapy session transcripts. It is much more likely
      that the facets of experience surface in this context than during a single
      interview or in a self-administered questionnaire. Using the Grid of Problematic
      States, designed to assess contents emerging in patients' transcripts, the
      authors analyzed the first 18 psychotherapy sessions with three female patients
      suffering from NPD and treated by therapists of the cognitive-constructivist
      school specializing in personality disorders. The three patients' dominant states
      of mind were characterized by anger, feeling excluded from groups, feelings of
      being harmed, and distrust toward others. The authors discuss the results and
      their implications for future research and for the definition of NPD in future
      editions of the Diagnostic and Statistical Manual of Mental Disorders.

PMID- 18815999
TI  - Patients' outcome expectancies and their impression of suitability as predictors
      of treatment outcome.
AB  - In treatment studies, the correlation of patients' outcome expectancies and their
      impression of treatment suitability with treatment outcome shows a contradictory
      pattern. It seems that a significant correlation can be shown only if outcome is
      measured with posttherapy scores or with retrospective success ratings but not if
      outcome is operationalized as any form of pre-post change scores. This study with
      499 outpatients (222 with anxiety disorders, 63 with affective disorders, 136
      with both anxiety and depression, and 78 with other disorders) examines whether
      this difference in the correlation pattern can be replicated by simultaneously
      using three kinds of outcome assessment. Three subscales of the Patients' Therapy
      Expectation and Evaluation questionnaire (Hope of Improvement, Fear of Change,
      and Suitability) were correlated with the treatment outcome. Results confirm the
      hypothesized model. Possible explanations of this pattern of results are
      discussed.

PMID- 18816001
TI  - Group interpersonal psychotherapy for low-income women with posttraumatic stress
      disorder.
AB  - The aim of this study was to assess the efficacy of group interpersonal
      psychotherapy (IPT) for low-income women with chronic posttraumatic stress
      disorder (PTSD) subsequent to interpersonal trauma. Non-treatment-seeking
      predominantly minority women were recruited in family planning and gynecology
      clinics. Individuals with interpersonal trauma histories (e.g., assault, abuse,
      and molestation) who met criteria for current PTSD (N=48) were randomly assigned
      to treatment or a wait list. Assessments were conducted at baseline, treatment
      termination, and 4-month follow-up; data analysis used a mixed-effects regression
      approach with an intent-to-treat sample. The results showed that IPT was
      significantly more effective than the wait list in reducing PTSD and depression
      symptom severity. IPT participants also had significantly lower scores than
      waitlist individuals on four interpersonal functioning subscales: Interpersonal
      Sensitivity, Need for Social Approval, Lack of Sociability, and Interpersonal
      Ambivalence.

PMID- 18816002
TI  - Psychotherapy expertise in Singapore: A qualitative investigation.
AB  - Personal characteristics, developmental influences, and therapy practices of nine
      peer-nominated expert psychotherapists practicing in the diverse country of
      Singapore were identified using qualitative methods. Sixteen themes were
      organized within four categories: (a) personal characteristics (empathic,
      nonjudgmental, respectful); (b) developmental influences (experience, self
      awareness, humility, self-doubt); (c) approach to practice (balance between
      support and challenge, flexible therapeutic stance, empowerment/strength-based
      approach, primacy of the therapeutic alliance, comfortable addressing
      spirituality, embraces working within a multicultural context); and (d) ongoing
      professional growth (professional development practices, benefits of
      teaching/training others, challenges to professional development in Singapore).
      Cross-cultural comparisons between this study and Jennings and Skovholt's (1999)
      study of Minnesota expert psychotherapists found considerable overlap of themes.
      Implications for research and practice of psychotherapy are offered.

PMID- 18816003
TI  - Mental states as part of countertransference responses in psychotherapists facing
      reports of traumatic events of mourning and sexual violence.
AB  - The study aims to compare the mental states and countertransference responses of
      92 psychodynamically oriented psychotherapists, male and female, experienced and
      inexperienced, facing written reports of real patients who experienced traumatic
      events. Two vignettes were presented: one of a sexual violence, the other the
      sudden death of a significant person. The Mental States Rating System (MSRS;
      Bouchard, Picard, Audet, Brisson, & Carrier, 1998), the MSRS Self-Report
      (Goldfeld & Bouchard, 2004), and the Inventory of Countertransference Behavior
      (ICB; Friedman & Gelso, 2000) were used. Results showed that the mourning
      vignette led to more reflective responses (MSRS) and the rape case was associated
      with more negative countertransference reactions (ICB). Female participants were
      more reflective (MSRS); male therapists used less mentalized states (MSRS Self
      Report) and expressed more negative reactions (ICB) for both scenarios.
      Experienced therapists showed more positive reactions on the ICB. The construct
      validity of the instruments is discussed in relation to the findings.

PMID- 18816004
TI  - Predictors of therapeutic outcome and process.
AB  - This article presents an intensive study of the outcome and process of the
      psychotherapeutic treatments conducted at the Blanquerna Psychotherapy Service in
      Barcelona. It analyzes in detail the relation between outcome (improvement) and
      process (therapeutic alliance). Specifically, it discusses (a) the therapeutic
      process in terms of the relation between therapeutic alliance and psychotherapy
      outcome and (b) the effects of the temporary weakening of the therapeutic
      alliance and temporary symptomatic relapse on therapeutic outcome and process.
      Two hundred thirty-nine clients were included in the study, and the assessment
      instruments were the CORE Outcome Measure and the short version of the Working
      Alliance Inventory. In addition to good outcome of psychotherapy and maintenance
      of therapeutic change after treatment, the results also demonstrated the
      significance of different aspects of the therapeutic alliance as predictors of
      the therapeutic outcome and process.

PMID- 18816005
TI  - Supervisors' reports of the effects of supervisor self-disclosure on supervisees.
AB  - Using consensual qualitative research, researchers interviewed 16 supervisors
      regarding their use of self-disclosure in supervision. Supervisors reported that
      their prior training in supervisor self-disclosure (SRSD) came via didactic
      sources and encouraged judicious use of SRSD. Supervisors used SRSD to enhance
      supervisee development and normalize their experiences; supervisors did not use
      SRSD when it derailed supervision or was developmentally inappropriate for
      supervisees. In describing specific examples of the intervention, SRSD occurred
      in good supervision relationships, was stimulated by supervisees struggling, was
      intended to teach or normalize, and focused on supervisors' reactions to their
      own or their supervisees' clients. SRSD yielded largely positive effects on
      supervisors, supervisees, the supervision relationship, and supervisors'
      supervision of others.

PMID- 18816006
TI  - Structural changes in counselor trainee intention use and clients' session
      evaluation.
AB  - Profile analysis and Pathfinder Network Analysis (Schvaneveldt, 1990) were used
      to examine changes in procedural knowledge and procedural structural knowledge,
      respectively, of 32 counselor trainees and to examine convergence in their
      procedural knowledge and procedural structural knowledge with the procedural
      knowledge structure of 42 experienced counselors. Procedural knowledge was
      derived from the pattern and level of intention use (Hill & O'Grady, 1985) in a
      pre- and posttraining counseling session. Procedural structural knowledge was
      derived from the co-occurrence of the intentions used in these two counseling
      sessions. Only counselor trainees' structure of intention use changed from pre-
      to posttraining, becoming more similar to the structure of intention use of the
      experienced counselors. At both pre- and posttraining, when trainees' structure
      of intention use was more similar to that of experienced counselors, their
      clients rated counseling sessions as smoother (pre- and posttraining) and deeper
      (posttraining only). The use of knowledge structures as a criterion for assessing
      the effectiveness of counseling skills training is discussed.

PMID- 18816007
TI  - Letters in cognitive analytic therapy: The patient's experience.
AB  - Patient perspectives on how therapeutic letters contributed to their experience
      of cognitive analytic therapy (CAT) were investigated. Eight patients took part
      in semistructured interviews. A grounded, thematic analysis of their accounts
      suggested four general processes. First, letters offered a tangible, lasting
      framework for the assimilation of a new perspective about themselves and their
      relationships and facilitated coping with a complex range of emotions and risks
      this awareness required. Second, they demonstrated therapists' commitment to
      patients' growth. Third, they helped to teach participants about the therapy
      process as an example of an interpersonal exchange. Fourth, they helped
      participants consider how they wished to share personal information. These data
      offer a more complex understanding of this standard CAT intervention. Although
      some findings are consistent with CAT theory, the range of emotional dilemmas
      associated with letters has not received specific attention. Clinical
      implications are discussed.

PMID- 18816008
TI  - An empirical analysis of autobiographical memory specificity subtypes in brief
      emotion-focused and client-centered treatments of depression.
AB  - Overgeneral autobiographical memory (ABM) disclosure has been established as a
      key cognitive marker of clinical depression in experimental research studies. To
      determine the ecological validity of these findings for psychotherapy treatments
      of depression, the present study investigated the relationship between change in
      level of depression and ABM specificity in the context of early, middle, and late
      therapy session transcripts selected from 34 clients undergoing emotion-focused
      therapy and client-centered therapy in the York I Depression Study. A
      hierarchical linear modeling analysis demonstrated that clients disclosed
      significantly more specific ABMs over the course of therapy. There were no
      differences in ABM specificity between treatment groups. There was also no
      evidence that increased specificity differentiated between recovered and
      unchanged clients at treatment termination.

PMID- 18816009
TI  - Guided self-help for binge eating/purging anorexia nervosa before inpatient
      treatment.
AB  - The goal of this study was to develop a cognitive-behavioral self-help manual for
      anorexia nervosa. Patients diagnosed with anorexia nervosa (N=102), binge
      eating/purging type (AN-B/P), were consecutively assigned to one of two
      conditions: 6-week manualized guided self-help or a wait-list control. All
      patients thereafter received inpatient treatment in a hospital for behavioral
      medicine. The primary outcome variable was the number of days in inpatient
      treatment. Secondary outcome variables were measures of psychopathology. Results
      showed that duration of inpatient treatment was significantly shorter (by 5.2
      days) among participants receiving guided self-help. Body image, slimness ideal,
      general psychopathology, and some bulimic symptoms improved significantly during
      self-help. The authors conclude that, to increase effects of therapist-guided
      self-help in AN-B/P, additional variants of a self-help manual should be tried in
      different therapeutic settings.

PMID- 18816010
TI  - Individual versus group cognitive-behavioral treatment for obsessive-compulsive
      disorder: a controlled pilot study.
AB  - This study sought to examine the effectiveness of group and individual cognitive
      behavioral treatment (CBT) and to compare the results with those of a wait-list
      control group among a sample of patients with obsessive-compulsive disorder
      (OCD). Fifty-seven individuals diagnosed with OCD were evaluated pre- and
      posttreatment with the Yale-Brown Obsessive Compulsive Scale and the Hamilton
      Rating Scales for Anxiety and Depression. Both group and individual CBT obtained
      statistically significant reductions in anxiety and depressive symptoms. Patients
      in individual treatment achieved a statistically significant reduction in OCD
      symptoms compared with those in group treatment, but their dropout rate was twice
      as high. Patients with symmetry and order rituals presented less improvement in
      anxiety symptoms than those with other rituals. Associated general symptoms were
      lower in patients receiving either mode of CBT compared with wait-list
      participants. The authors found that individual treatment is more effective in
      reducing obsessive-compulsive symptoms than group treatment.

PMID- 18816011
TI  - From symptom relief to interpersonal change: Treatment outcome and effectiveness
      in inpatient psychotherapy.
AB  - This study evaluated the impact of psychodynamic inpatient psychotherapy on
      patients' psychological distress and interpersonal problems during the course of
      treatment and 1 year later. A total of 156 patients were assessed with the
      Symptom Checklist-90-Revised and the Inventory of Interpersonal Problems at
      intake, 4 weeks later, and at the end of therapy. The follow-up assessment was
      conducted 1 year later. Results support psychodynamic approaches as well as the
      phase model, which stresses that the goals to be achieved by psychotherapeutic
      interventions are not only improvement of well-being and symptoms but also
      changes in interpersonal behavior. Consequently, on a long-term basis, the first
      4 weeks of therapy seem to be insufficient, especially for adequate changes on
      the interpersonal level.

PMID- 18816013
TI  - Bayesian analysis of heterogeneity in the distribution of binding properties of
      immobilized surface sites.
AB  - Once a homogeneous ensemble of a protein ligand is taken from solution and
      immobilized to a surface, for many reasons the resulting ensemble of surface
      binding sites to soluble analytes may be heterogeneous. For example, this can be
      due to the intrinsic surface roughness causing variations in the local
      microenvironment, nonuniform density distribution of polymeric linkers, or
      nonuniform chemical attachment producing different protein orientations and
      conformations. We previously described a computational method for determining the
      distribution of affinity and rate constants of surface sites from analysis of
      experimental surface binding data. It fully exploits the high signal/noise ratio
      and reproducibility provided by optical biosensor technology, such as surface
      plasmon resonance. Since the computational analysis is ill conditioned, the
      previous approach used a regularization strategy assuming a priori all binding
      parameters to be equally likely, resulting in the broadest possible parameter
      distribution consistent with the experimental data. We now extended this method
      in a Bayesian approach to incorporate the opposite assumption, i.e., that the
      surface sites a priori are expected to be uniform (as one would expect in free
      solution). This results in a distribution of binding parameters as close to
      monodispersity as possible given the experimental data. Using several model
      protein systems immobilized on a carboxymethyl dextran surface and probed with
      surface plasmon resonance, we show microheterogeneity of the surface sites in
      addition to broad populations of significantly altered affinity. The
      distributions obtained are highly reproducible. Immobilization conditions and the
      total surface density of immobilized sites can have a substantial impact on the
      functional distribution of the binding sites.

PMID- 18816014
TI  - Synthesis and self-assembly of thio derivatives of calix[4]arene on noble metal
      surfaces.
AB  - Self-assembled monolayers (SAMs) provide a simple route to functionalize
      electrode surfaces with organic molecules. Herein we use cavity-containing
      derivatives of calix[4]arenes in SAMs. Bound to noble metal surface, the
      assembled molecules are candidates to serve as molecular sieves for H 2 molecules
      and H (+) ions, which could have relevance for fuel cell applications. Tetra- O
      alkylated calix[4]arenes with thiolacetate and thiolamide wide-rim anchoring
      groups in cone and partial-cone conformations were designed, synthesized and self
      assembled onto Au, Pt, and Pd surfaces. The resulting SAMs were systematically
      examined. Single crystal X-ray diffraction of 5,11,17,23-tetrakis(thioacetyl)
      25,26,27,28-tetra- i-propoxycalix[4]arene confirmed the cone conformation and
      revealed the cavity dimensions of the SAMs that were formed by immersing noble
      metal substrates (Au, Pt and Pd deposited on Si-wafers) in solutions of
      calix[4]arenes. Surface characterization techniques including ellipsometry,
      cyclic voltammetry (CV) and X-ray photoelectron spectroscopy (XPS) were used,
      indicating that the metal surface is terminated with a monomolecular layer.
      Experimental thicknesses obtained from the ellipsometry are consistent with the
      calculated values. CV results showed 50 to 80% physical passivation against the
      Fe(CN) 6 (3-/4-) couple, implying an overall relatively low concentration of
      defects and pinholes in the films. The binding energies of the S2p core level in
      the XPS were consistent with the literature values and revealed that up to 3.2
      out of four anchoring groups were bonded to the noble metal surface.

PMID- 18816015
TI  - Microemulsions with alkyldimethyl phosphine oxides and alkyldiethyl phosphine
      oxides.
AB  - Alkyldimethyl phosphine oxides (C n DMPO) as well as alkyldiethyl phosphine
      oxides (C n DEPO) with chain lengths of n = 10 (decyl), 12 (dodecyl), and 14
      (tetradecyl) were synthesized and purified to study how the formation of
      microemulsions depends on the size of the headgroup and on the length of the
      alkyl chain. For that purpose, equal amounts of water and n-octane were taken and
      surfactant was added to solubilize the two solvents. The resulting fish-shaped
      phase diagrams for C 10DEPO, C 12DEPO, and C 14DEPO show that the longer the
      hydrophobic chain the more efficient the surfactant. Simultaneously, the
      extension of the lamellar phase (L alpha) shifts toward lower total mass
      fractions gamma of the surfactant, i.e., the tendency to form lyotropic liquid
      crystals (LCs) increases. These trends are well-known for nonionic alkyl ethylene
      oxides and can thus be interpreted accordingly. What is astonishing, however, is
      the significant influence the size of the short side chains has. Replacing two
      methyl groups by two ethyl groups leads to a drastic drop of the three-phase
      region toward lower temperatures, while the efficiency remains nearly unchanged.
      Moreover, the tendency to form LCs decreases significantly.

PMID- 18816016
TI  - Structure of self-organized multilayer nanoparticles for drug delivery.
AB  - The combined use of cryo-TEM, dynamic light scattering, and small-angle X-ray and
      neutron scattering techniques allows a detailed structural model of complex
      pharmaceutical preparations of soybean lecithin/chitosan nanoparticles used as
      drug vectors to be worked out. Charge-driven self-organization of the lipid(
      )/polysaccharide(+) vesicles occurs during rapid injection, under mechanical
      stirring, of an ethanol solution of soybean lecithin into a chitosan aqueous
      solution. We conclude that beyond the charge inversion region of the phase
      diagram, i.e., entering the redissolution region, the initial stages of particle
      formation are likely to be affected by a re-entrant condensation effect at the
      nanoscale. This behavior resembles that at the mesoscale which is well-known for
      polyion/amphiphile systems. Close to the boundary of the charge inversion region,
      nanoparticle formation occurs under a maximum condensation condition at the
      nanoscale and the complexation-aggregation process is driven toward a maximum
      multilamellarity. Interestingly, the formulation that maximizes vesicle
      multilamellarity corresponds to that displaying the highest drug loading
      efficiency.

PMID- 18816017
TI  - Size ratio effects on interparticle interactions and phase behavior of
      microsphere-nanoparticle mixtures.
AB  - We investigate the interparticle interactions and phase behavior of microsphere
      nanoparticle mixtures of high charge asymmetry and varying size ratio. In the
      absence of nanoparticles, negligibly charged microspheres flocculate as a result
      of van der Waals interactions. Upon addition of a lower critical nanoparticle
      volume fraction, the microspheres are stabilized by the formation of nanoparticle
      halos around each microsphere. , A weak attraction between the two species leads
      to a pronounced enhancement of the effective nanoparticle concentration near the
      microsphere surface relative to the bulk solution. Above an upper critical
      nanoparticle volume fraction, the microspheres undergo reentrant gelation. Binary
      mixtures, in which the effective nanoparticle size is reduced at a fixed
      microsphere diameter, exhibit a narrow window of stability that ultimately
      disappears with increasing ionic strength. By contrast, binary mixtures of
      varying microsphere diameter are stabilized at similar nanoparticle volume
      fractions and exhibit a broader window of stability with decreasing size ratio.
      This unexpected observation may arise from the reduced attraction between smaller
      microspheres because negligible differences in nanoparticle halo formation are
      observed in these mixtures.

PMID- 18816018
TI  - Aqueous foam drainage characterized by terahertz spectroscopy.
AB  - Aqueous foam drainage has been studied using terahertz (THz) spectroscopy. Water
      is highly absorbing of THz radiation, allowing drainage to be determined based on
      water content at respective foam height. These drainage profiles were validated
      using a model constructed from published equations and tailored to this specific
      study. In addition, a slow-draining foam was scanned to produce a two-dimensional
      foam image.

PMID- 18816019
TI  - Rapid estimation of bacteria by a fluorescent gold nanoparticle-polythiophene
      composite.
AB  - Herein we present a facile method for rapid quantitation of bacterial cells over
      several logarithmic dilutions. The quantitation is based on loss of the
      fluorescence intensity of a positively charged Au nanoparticle-polythiophene
      composite in the presence of bacterial cells. The present method allowed
      estimation of both Gram-positive and Gram-negative bacteria with cells as low as
      1000. Transmission electron microscopic investigations revealed attachment of the
      composite with bacteria with no discernible change in the morphology of the
      cells. Further, dynamic light scattering experiments indicated preferential
      attachment of smaller composite particles over larger ones, which were also
      attached at higher bacterial concentrations. The ease of operation with minimal
      sample manipulation steps, high sensitivity, quantitative detection, and its
      generality offer specific advantages over conventional methods.

PMID- 18816020
TI  - pH-dependent self-assembly of polystyrene-block-poly((sulfamate
      carboxylate)isoprene) copolymer in aqueous media.
AB  - The amphiphilic polystyrene- block-poly((sulfamate-carboxylate)isoprene) (PS
      PISC) diblock copolymer was synthesized from the precursor diblock copolymer
      polystyrene- block-isoprene by reaction with chlorosulfonyl isocyanate. The
      structure and behavior of self-assembled PS-PISC nanoparticles was studied in
      alkaline and acidic aqueous solutions by a combination of static and dynamic
      light scattering, analytical ultracentrifugation, atomic force and cryogenic
      transmission electron microscopies, NMR spectroscopy, potentiometric titration,
      and fluorometry using pyrene as a polarity-sensitive fluorescent probe. It was
      found that PS-PISC exists in aqueous solutions in the form of micellar
      aggregates. The aggregation tendency increases with decreasing effective charge
      density in the shell, that is, with decreasing pH of the solution, and aggregates
      found in alkaline aqueous media have much smaller molar masses than those formed
      in acidic media. The latter are dense, collapsed structures with immobile PISC
      domains in which most of the COOH and NH 2 (+)SO 3 (-) groups are buried inside
      of the nanoparticles. The swelling of PISC domains and disentanglement of PISC
      chains after addition of a base are slow processes occurring on the time scale of
      days.

PMID- 18816021
TI  - Hydrogen-bonded polymer multilayers probed by neutron reflectivity.
AB  - We present a neutron reflectivity study of the internal structure of multilayers
      made of a weak polyelectrolyte and a neutral component where interactions between
      adjacent layers are controlled by hydrogen-bonding. We found the degree of
      interpenetration of polymer layers expressed as the interlayer roughness to be
      strongly correlated with the strength of intermolecular interactions between the
      adjacent layers. In addition, polymer layers become more diffuse with a distance
      from the substrate. Our results demonstrate that hydrogen-bonded films exhibit a
      close correlation between their structure and properties, which is essential for
      various applications.

PMID- 18816022
TI  - Entrapping desired amounts of actin filaments and molecular motor proteins in
      giant liposomes.
AB  - We have successfully prepared cell-sized giant liposomes encapsulating desired
      amounts of actoHMM, a mixture of actin filament (F-actin) and heavy meromyosin
      (HMM, an actin-related molecular motor), in the presence of 5 mM MgCl 2 and 50 mM
      KCl. We employed a spontaneous transfer method to prepare those liposomes. In the
      absence of HMM, F-actin was distributed homogeneously inside the liposomes. In
      contrast, when F-actin was encapsulated in liposomes together with HMM, network
      structures were generated. Such network structures are attributable to the cross
      linking of F-actin by HMM.

PMID- 18816023
TI  - Electronic structure study of thermal intraconversions of some dicyclopenta-fused
      polycyclic aromatic compounds.
AB  - The electronic structure of dicyclopenta[de,mn]anthracene (P1), dicyclopenta[
      de,kl]anthracene (P2), and dicyclopenta[jk,mn]phenanthrene (P3) and their mutual
      isomerization processes are investigated using density functional theory. Two
      mechanisms for the thermal intraconversion of P1 to P2 were found. The first
      mechanism occurs via ethynylaceanthrylene (I0), and the second involves a 1,2
      hydrogen shift. It is supposed that I0 is initially formed during the flash
      vacuum pyrolysis experiments, eventually rearranging to P2 on high temperatures.
      The energetics of the latter mechanism also indicate that P1 isomerizes to P2.
      The mechanism for a transformation of P2 to P3 is based on a ring
      contraction/ring conversion process and requires extremely high temperatures. Our
      investigation is in accord with the experimental results: unsuccessful synthesis
      of P1, stability of P2 at high temperature, and formation of P3 under extreme
      temperature regime.

PMID- 18816024
TI  - Using molecular docking, 3D-QSAR, and cluster analysis for screening structurally
      diverse data sets of pharmacological interest.
AB  - In this study, we propose a drug design approach which includes docking,
      molecular fingerprints based cluster analysis, and 'induced' descriptors based
      receptor-dependent 3D-QSAR. The method was shown to be very useful for screening
      and modeling structurally diverse data sets of pharmacological interest.
      Different from other receptor-dependent 3D-QSAR, no ambiguous alignments are
      required for the construction of the models, and the computational cost is
      relatively lower. Moreover, 'induced' descriptors were shown to be very powerful
      in "capturing" ligand-receptor intermolecular interactions. The methodology was
      validated for eight data sets sampled from the literature and from public
      databases: human sex hormone-binding globulin, human corticosteroid-binding
      globulin, anthrax lethal factor, HIV-1 reverse transcriptase, neuraminidase A,
      thrombin, trypsin, and Pneumocystis carinii dihydrofolate reductase data sets.
      The resulting models were interpretable; the constructed QSAR equations have high
      statistical significance and predictive strength; and the drug design solutions
      were shown to be useful for guiding ligand modification for the development of
      new inhibitors for a broad range of molecular targets.

PMID- 18816025
TI  - A study of the photochemistry of Diazo Meldrum's acid by ultrafast time-resolved
      spectroscopies.
AB  - The photochemistry of Diazo Meldrum's acid (DM) was investigated by fs time
      resolved UV-vis and IR spectroscopic methods. UV (266 nm) excitation of DM pumps
      the molecule to the S 5 and S 7 excited states. After fast internal conversion
      (IC), the S 2 state is formed, which will undergo Wolff rearrangement to form
      vibrationally excited ketene, which relaxes in 9 ps. The S 2 state will also
      relax to the S 1 state, which isomerizes to diazirine, fragments to form carbene,
      and relaxes further to the ground state of DM. The singlet carbene absorbs at 305
      nm, is formed within 300 fs of the laser pulse, and has a lifetime of 2.3 ps in
      acetonitrile. The lifetime of DM in the S 2 and S 1 states is less than 300 fs.
      The quantum efficiency of DM decomposition is approximately 50% in chloroform
      with 266 nm excitation.

PMID- 18816026
TI  - Thermochemistry of 2- and 3-thiopheneacetic acids: calorimetric and computational
      study.
AB  - The enthalpies of formation in the condensed and gas states, Delta f H m degrees
      (cd) and Delta f H m degrees (g), of 2- and 3-thiopheneacetic acids were derived
      from their respective enthalpies of combustion in oxygen, measured by a rotating
      bomb calorimeter, and the variation of vapor pressure with temperature determined
      by the Knudsen effusion technique. Theoretical calculations at the G3 level were
      performed, and a study on molecular and electronic structure of the compounds has
      been carried out. Calculated Delta f H m degrees (g) values using atomization and
      isodesmic reactions are compared with the experimental data. Experimental and
      theoretical results show that the 3-thiopheneacetic acid is thermodynamically
      more stable than the 2-isomer.

PMID- 18816027
TI  - Comprehensive analysis of the hydrogen bond network morphology and OH stretching
      vibrations in protonated methanol-water mixed clusters, H(+)(MeOH)1(H2O)n (n = 1
      8).
AB  - Density functional theory (DFT) calculations of protonated methanol-water mixed
      clusters, H (+)(MeOH) 1(H 2O) n ( n = 1-8), were extensively carried out to
      analyze the hydrogen bond structures of the clusters. Various structural isomers
      were energy optimized, and their relative energies with zero point energy
      corrections and temperature dependence of the free energies were examined.
      Coexistence of different morphological isomers was suggested. Infrared spectra
      were simulated on the basis of the optimized structures. The infrared spectra
      were also experimentally measured for n = 3-9 in the OH stretching vibrational
      region. The observed broad bands in the hydrogen-bonded OH stretch region were
      assigned in comparison with the simulations. From the DFT calculations, the
      preferential proton location was also investigated. Clear correlations between
      the excess proton location and the cluster morphology were found.

PMID- 18816028
TI  - Infrared multiple photon dissociation spectra of proton- and sodium ion-bound
      glycine dimers in the N-H and O-H stretching region.
AB  - The proton- and the sodium ion-bound glycine homodimers are studied by a
      combination of infrared multiple photon dissociation (IRMPD) spectroscopy in the
      N-H and O-H stretching region and electronic structure calculations. For the
      proton-bound glycine dimer, in the region above 3100 cm (-1), the present
      spectrum agrees well with one recorded previously. The present work also reveals
      a weak, broad absorption spanning the region from 2650 to 3300 cm (-1). This
      feature is assigned to the strongly hydrogen-bonded and anharmonic N-H and O-H
      stretching modes. As well, the shared proton stretch is observed at 2440 cm (-1).
      The IRMPD spectra for the proton-bound glycine dimer confirms that the lowest
      energy structure is an ion-dipole complex between N-protonated glycine and the
      carboxyl group of the second glycine. This spectrum also helps to eliminate the
      existence of any of the higher-energy structures considered. The IRMPD spectrum
      for the sodium ion-bound dimer is a much simpler spectrum consisting of three
      bands assigned to the O-H stretch and the asymmetric and symmetric NH 2
      stretching modes. The positions of these bands are very similar to those observed
      for the proton-bound glycine dimer. Numerous structures were considered and the
      experimental spectrum agrees with the B3LYP/6-31+G(d,p) predicted spectrum for
      the lowest energy structure, two bidentate glycine molecules bound to Na (+).
      Though some of the structures cannot be completely ruled out by comparing the
      experimental and theoretical spectra, they are energetically disfavored by at
      least 20 kJ mol (-1).

PMID- 18816029
TI  - Investigating the proton transferring route in a heteroaromatic compound part I:
      a trial to develop di- and trifunctional benzimidazole model compounds inducing
      the molecular packing structure with a hydrogen bond network.
AB  - Di- and trifunctional benzimidazole molecules, 1 and 2, have been synthesized as
      the model compounds to identify their molecular packing structure and hydrogen
      bond network, which is possibly involved in the proton transfer system belonging
      to its heteroaromatic functional groups. By carrying out the simple reaction
      between acid chloride and diamine, the desired benzimidazole model compounds are
      obtained with high yield above 60%. The comparison studies between the model
      compounds and benzimidazole reveal that the model compounds show well-packing
      structure with intermolecular hydrogen bonds similar to those observed in
      benzimidazole. The presence of solvent with 2 leads to the unique intermolecular
      hydrogen bonds between one molecule of 2 and six molecules of solvent (i.e., 2
      propanol) resulting in the solvent-assisted intramolecular hydrogen bond network
      among benzimidazole functional groups. The comparative studies of the effect of
      temperature on the packing structure and hydrogen bond in the model compounds
      indicate that the development of the benzimidazole unit from monofunctional to
      difunctional and finally trifunctional enhances the intermolecular interaction
      between the molecules and results in the stronger molecular packing structure of
      the compounds. A study on proton conductivity by preparing the sulfonated
      poly(ether ether ketone) (SPEEK) membranes with benzimidazole, 1, and 2 for 15
      phr equivalent to benzimidazole group clarifies (i) incorporation of
      benzimidazole compounds improves the proton conductivity of SPEEK in dry
      condition and (ii) the increase in proton conductivity is relevant to the number
      of benzimidazole group on molecule.

PMID- 18816030
TI  - Electronic state of the molecular oxygen released by catalase.
AB  - In catalases, the high redox intermediate known as compound I (Cpd I) is reduced
      back to the resting state by means of hydrogen peroxide in a 2-electron reaction
      [Cpd I (Por(*+)-Fe(IV)O) + H(2)O(2) --> Enz (Por-Fe(III)) + H(2)O + O(2)]. It has
      been proposed that this reaction takes place via proton transfer toward the
      distal His and hydride transfer toward the oxoferryl oxygen (H(+)/H(-) scheme)
      and some authors have related it to singlet oxygen generation. Here, we consider
      the possible reaction schemes and qualitatively analyze the electronic state of
      the species involved to show that the commonly used association of the H(+)/H(-)
      scheme with singlet oxygen production is not justified. The analysis is
      complemented with density functional theory (DFT) calculations for a gas-phase
      active site model of the reactants and products.

PMID- 18816031
TI  - A computational study on some viable targets for gas-phase synthesis of metal
      complexes of the cyclic (B6C)-2 and their bonding pattern.
AB  - In this account, a detailed computational study is conducted to verify the
      geometric, energetic, and electronic properties of the planar cyclic (B 6C) (-2)
      (as the simplest carrier of hexacoordinate carbon) within some metal complexes.
      The [M(B 6C)] ((-)) (M = Li, Na, K) and [M(B 6C)] (M = Be, Mg, Ca) series are
      employed for this purpose. Relevant ab initio calculations at both DFT and post
      HF levels vividly demonstrate that this dianion is stabilized considerably in the
      electric field generated by cations, whereas the geometrical and electronic
      properties of this ring remain almost intact in these complexes. The
      complementary topological analysis of charge densities confirms that cyclic (B
      6C) (-2) within these complexes exhibits the same topological patterns as the
      naked dianion, thus confirming the presence of an unusual charge density
      distribution in this dianion. An electrostatic model is proposed that not only
      qualitatively but also quantitatively explains the observed computational trends
      in these complexes. This model successfully traces the polarization of the
      central carbon atom of the ring in the presence of a hard, multiply charged
      cation. To facilitate experimental detection, the photoelectron spectra of the
      [M(B 6C)] ((-)) (M = Li, Na, K) series are computed and the dominant features are
      extracted. Although considered species are not global minima on their potential
      energy hypersurfaces, their kinetic stabilities are verified and demonstrated
      unequivocally.

PMID- 18816032
TI  - Transient phenomena in the pulse radiolysis of oxoisoaporphine derivatives in
      acetonitrile.
AB  - The absorption-spectral and kinetic behavior of radical ions and triplet states
      of two oxoisoaporphine derivatives, 2,3-dihydrooxoisoaporphine (2,3-DHOA) and 5
      methoxy-2,3-dihydrooxoisoaporphine (5-MeO-2,3-DHOA), have been studied by UV-vis
      spectrophotometric pulse radiolysis in a neat acetonitrile saturated with argon
      and oxygen at room temperature. The radical anions of 2,3-DHOA and 5-MeO-2,3-DHOA
      are characterized by intense absorption maxima located at lambda max = 605 and
      590 nm, with molar absorption coefficients 605 = 5600 M (-1) cm (-1) and 590 =
      4900 M (-1) cm (-1), respectively. Both radical anions decay via first-order
      kinetics with the rate constants in the range (1.5-2.6) x 10 (5) s (-1),
      predominantly through protonation by adventitious water forming neutral
      hydrogenated radicals. Oxygen insensitive, the radical cations of 2,3-DHOA are
      characterized by a strong nondescript absorption band with no distinct lambda max
      in the range 350-450 nm. On the other hand, the radical cations of 5-MeO-2,3-DHOA
      are characterized by the distinctive absorption band with lambda max = 420 nm.
      The experimental spectra of the neutral-hydrogenated radicals and the triplet
      excited states derived from 2,3-DHOA and 5-MeO-2,3-DHOA are in accordance with
      the spectra observed previously during laser flash photolysis ( De la Fuente, J.
      R. ; et al. J. Phys. Chem. 2005, 109, 5897 ). Most of the transient spectra
      generated radiolytically are adequately reproduced by quantum mechanical
      semiempirical PM3 and ZINDO/S methods.

PMID- 18816033
TI  - Vibrational spectra of alpha-amino acids in the zwitterionic state in aqueous
      solution and the solid state: DFT calculations and the influence of hydrogen
      bonding.
AB  - The zwitterionic forms of the two simplest alpha-amino acids, glycine and l
      alanine, in aqueous solution and the solid state have been modeled by DFT
      calculations. Calculations of the structures in the solid state, using PW91 or
      PBE functionals, are in good agreement with the reported crystal structures, and
      the vibrational spectra computed at the optimized geometries provide a good fit
      to the observed IR and Raman spectra in the solid state. DFT calculations of the
      structures and vibrational spectra of the zwitterions in aqueous solution at the
      B3-LYP/cc-pVDZ level were found to require both explicit and implicit solvation
      models. Explicit solvation was modeled by inclusion of five hydrogen-bonded water
      molecules attached to each of the five possible hydrogen-bonding sites in the
      zwitterion and the integration equation formalism polarizable continuum model
      (IEF-PCM) was employed, providing a satisfactory fit to observed IR and Raman
      spectra. Band assignments are reported in terms of potential-energy
      distributions, which differ in some respects to those previously reported for
      glycine and l-alanine.

PMID- 18816034
TI  - Comment on "Local lattice structure study of the octahedral (CrO6)9- clusters for
      Cr3+ ion doping in a variety of oxide crystals by simulating the corresponding
      EPR and optical spectra".

PMID- 18816035
TI  - Vibrational spectra of anhydrous and monohydrated caffeine and theophylline
      molecules and crystals.
AB  - Density functional theory and classical molecular dynamics simulations are used
      to investigate the vibrational spectra of caffeine and theophylline anhydrous and
      monohydrate molecules and those of their crystalline anhydrous and monohydrated
      states, with emphasis in the terahertz region of the spectra. To better
      understand the influence of water in the monohydrate crystal spectra, we analyze
      the vibrational spectra of water monomer, dimer, tetramer, and pentamer, and also
      those of liquid water at two different temperatures. In small water clusters, we
      observe the progressive addition of translational and librational modes to the
      terahertz region of the spectra. The water spectra predicted by rigid and
      flexible water models is examined with classical molecular dynamics, and the
      respective peaks, especially in the terahertz region, are compared with those
      found in the small clusters. Similar analysis done for caffeine and theophylline
      monohydrate molecules using density functional theory clearly shows the presence
      of water modes in the librational states and in the water stretching region.
      Molecular dynamics of caffeine and theophylline anhydrous and monohydrate
      crystals reveal the influence of vibrations from the molecule-molecule (caffeine
      or theophylline) crystal stacks and those from the water-molecule interactions
      found in the monohydrate molecules and new modes from molecule-molecule, water
      molecule, and water-water hydrogen bonding interactions arising from collective
      effects in the crystal structure. Findings illustrate challenges of terahertz
      technology for the detection of specific substances in condensed phases.

PMID- 18816037
TI  - Mechanism of the hydration of carbon dioxide: direct participation of H2O versus
      microsolvation.
AB  - Thermochemical parameters of carbonic acid and the stationary points on the
      neutral hydration pathways of carbon dioxide, CO 2 + nH 2O --> H 2CO 3 + ( n -
      1)H 2O, with n = 1, 2, 3, and 4, were calculated using geometries optimized at
      the MP2/aug-cc-pVTZ level. Coupled-cluster theory (CCSD(T)) energies were
      extrapolated to the complete basis set limit in most cases and then used to
      evaluate heats of formation. A high energy barrier of approximately 50 kcal/mol
      was predicted for the addition of one water molecule to CO 2 ( n = 1). This
      barrier is lowered in cyclic H-bonded systems of CO 2 with water dimer and water
      trimer in which preassociation complexes are formed with binding energies of
      approximately 7 and 15 kcal/mol, respectively. For n = 2, a trimeric six-member
      cyclic transition state has an energy barrier of approximately 33 (gas phase) and
      a free energy barrier of approximately 31 (in a continuum solvent model of water
      at 298 K) kcal/mol, relative to the precomplex. For n = 3, two reactive pathways
      are possible with the first having all three water molecules involved in hydrogen
      transfer via an eight-member cycle, and in the second, the third water molecule
      is not directly involved in the hydrogen transfer but solvates the n = 2
      transition state. In the gas phase, the two transition states have comparable
      energies of approximately 15 kcal/mol relative to separated reactants. The first
      path is favored over in aqueous solution by approximately 5 kcal/mol in free
      energy due to the formation of a structure resembling a (HCO 3 (-)/H 3OH 2O (+))
      ion pair. Bulk solvation reduces the free energy barrier of the first path by
      approximately 10 kcal/mol for a free energy barrier of approximately 22 kcal/mol
      for the (CO 2 + 3H 2O) aq reaction. For n = 4, the transition state, in which a
      three-water chain takes part in the hydrogen transfer while the fourth water
      microsolvates the cluster, is energetically more favored than transition states
      incorporating two or four active water molecules. An energy barrier of
      approximately 20 (gas phase) and a free energy barrier of approximately 19 (in
      water) kcal/mol were derived for the CO 2 + 4H 2O reaction, and again formation
      of an ion pair is important. The calculated results confirm the crucial role of
      direct participation of three water molecules ( n = 3) in the eight-member cyclic
      TS for the CO 2 hydration reaction. Carbonic acid and its water complexes are
      consistently higher in energy (by approximately 6-7 kcal/mol) than the
      corresponding CO 2 complexes and can undergo more facile water-assisted
      dehydration processes.

PMID- 18816038
TI  - Determining the transition-state structure for different SN2 reactions using
      experimental nucleophile carbon and secondary alpha-deuterium kinetic isotope
      effects and theory.
AB  - Nucleophile (11)C/ (14)C [ k (11)/ k (14)] and secondary alpha-deuterium [( k H/
      k D) alpha] kinetic isotope effects (KIEs) were measured for the S N2 reactions
      between tetrabutylammonium cyanide and ethyl iodide, bromide, chloride, and
      tosylate in anhydrous DMSO at 20 degrees C to determine whether these isotope
      effects can be used to determine the structure of S N2 transition states.
      Interpreting the experimental KIEs in the usual fashion (i.e., that a smaller
      nucleophile KIE indicates the Nu-C alpha transition state bond is shorter and a
      smaller ( k H/ k D) alpha is found when the Nu-LG distance in the transition
      state is shorter) suggests that the transition state is tighter with a slightly
      shorter NC-C alpha bond and a much shorter C alpha-LG bond when the substrate has
      a poorer halogen leaving group. Theoretical calculations at the B3LYP/aug-cc-pVDZ
      level of theory support this conclusion. The results show that the experimental
      nucleophile (11)C/ (14)C KIEs can be used to determine transition-state structure
      in different reactions and that the usual method of interpreting these KIEs is
      correct. The magnitude of the experimental secondary alpha-deuterium KIE is
      related to the nucleophile-leaving group distance in the S N2 transition state (
      R TS) for reactions with a halogen leaving group. Unfortunately, the calculated
      and experimental ( k H/ k D) alpha's change oppositely with leaving group
      ability. However, the calculated ( k H/ k D) alpha's duplicate both the trend in
      the KIE with leaving group ability and the magnitude of the ( k H/ k D) alpha's
      for the ethyl halide reactions when different scale factors are used for the high
      and the low energy vibrations. This suggests it is critical that different
      scaling factors for the low and high energy vibrations be used if one wishes to
      duplicate experimental ( k H/ k D) alpha's. Finally, neither the experimental nor
      the theoretical secondary alpha-deuterium KIEs for the ethyl tosylate reaction
      fit the trend found for the reactions with a halogen leaving group. This
      presumably is found because of the bulky (sterically hindered) leaving group in
      the tosylate reaction. From every prospective, the tosylate reaction is too
      different from the halogen reactions to be compared.

PMID- 18816039
TI  - Matrix isolation infrared spectroscopic and density functional theoretical
      studies on the reactions of lanthanum atoms with acetylene.
AB  - Laser-ablated lanthanum atoms have been codeposited at 4 K with acetylene in
      excess argon. Products, La(C 2H 2), LaCCH 2, HLaCCH, and La 2(C 2H 2), 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 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- 18816040
TI  - Ozonolysis of oleic acid adsorbed to polar and nonpolar aerosol particles.
AB  - Single-particle kinetic studies of the reaction between oleic acid and O 3 have
      been conducted on two different types of core particles: polystyrene latex (PSL)
      and silica. Oleic acid was found to adsorb to both particle types in multilayer
      islands that resulted in an adsorbed layer of a total volume estimated to be less
      than one monolayer. The rate of the surface reaction between surface-adsorbed
      oleic acid and O 3 has been shown for the first time to be influenced by the
      composition of the aerosol substrate in a mixed organic/inorganic particle. A
      Langmuir-Hinshelwood mechanism was applied to the observed dependence of the
      pseudo-first-order rate constant with [O 3], and the resulting fit parameters for
      the ozone partition coefficient ( K O 3 ) and maximum first order rate constant (
      k 1,max ) suggest that the reaction proceeded faster on the less polar PSL core
      at lower [O 3] due to the increased residence time of O 3 on the PSL surface, but
      the reaction was ultimately more efficient on the silica surface at high [O 3].
      Values for the uptake coefficient, gamma oleic , for reaction of oleic acid on
      PSL spheres decrease from 2.5 x 10 (-5) to 1 x 10 (-5) with increasing [O 3] from
      4 to 25 ppm and overlap at high [O 3] with the estimated values for gamma oleic
      on silica, which decrease from 1.6 x 10 (-5) to 1.3 x 10 (-5). The relationship
      between gamma oleic and the more common expression for gamma O 3 is discussed.

PMID- 18816041
TI  - Photoprocesses of chloro-substituted p-benzoquinones.
AB  - The photochemistry of chloro-(ClBQ), dichloro-(2,5- and 2,6-Cl 2BQ), and
      trichloro-1,4-benzoquinone (Cl 3BQ) was studied in aqueous solution and/or in
      mixtures with acetonitrile. Final products are the corresponding hydroquinones
      (QH 2s) and 2-hydroxy-1,4-benzoquinones (QOHs). Three transients were detected by
      UV-vis absorption spectroscopy. The triplet state appears within the 20 ns 248 nm
      pulse and is converted within 0.1-1 micros into a photohydrate (HI aq). HI aq
      which is spectroscopically and kinetically separated from the triplet state
      decays within 5 ms, whereas the anion of the hydroxyquinone (QO (-)) grows in at
      ca. 500 nm in the 0.1-1 s time range. The proton formation and decay kinetics
      within 0.1-10 micros were observed by transient conductivity in the course of the
      reaction of the triplet state with water en route to HI aq at pH 4-9. Formation
      of QO (-) results in a permanent conductance. The efficient photoconversion of Cl
      n BQs at low concentrations (<0.2 mM) into QH 2s and HOQs is due to a redox
      reaction of Q with rearranged HI aq. The quantum yield of photoconversion at
      lambda irr = 254 nm is 0.8-1.2 for ClBQ or Cl 2BQs in aqueous acetonitrile and
      smaller (0.4) for Cl 3BQ. The yield of semiquinone radical ( (*)QH/Q (*-)) of Cl
      n BQs ( n = 1-4) in acetonitrile-water (1:1) is low (<20%) at low substrate
      concentration but is significantly increased upon addition of an H-atom donor,
      for example, 2-propanol. Other mechanisms involving (*)QH/Q (*-) radicals, such
      as quenching of the triplet state at enhanced Cl n BQ concentrations and H-atom
      abstraction from an organic solvent in mixtures with water, have also to be
      considered.

PMID- 18816042
TI  - Kinetics and mechanism of the NCN + NO2 reaction studied by experiment and
      theory.
AB  - The rate constant for the NCN + NO 2 reaction has been measured by a laser
      photolysis/laser-induced fluorescence technique in the temperature range of 260
      296 K at pressures between 100 and 500 Torr with He and N 2 as buffer gases. The
      NCN radical was produced from the photolysis of NCN 3 at 193 nm and monitored by
      laser-induced fluorescence with a dye laser at 329.01 nm. The rate constant was
      found to increase with pressure but decrease with temperature, indicating that
      the reaction occurs via a long-lived intermediate stabilized by collisions with
      buffer gas. The reaction mechanism and rate constant are also theoretically
      predicted for the temperature range of 200-2000 K and the He and N 2 pressure
      range of 10 (-4) Torr to 1000 atm based on dual-channel Rice-Ramsperger-Kassel
      Marcus (RRKM) theory with the potential energy surface evaluated at the
      G2M//B3LYP/6-311+G(d) level. In the low-temperature range (<700 K), the most
      favorable reaction is the barrierless association channel that leads to the
      intermediate complex (NCN-NO 2). At high temperature, the direct O-abstraction
      reaction with a barrier of 9.8 kcal/mol becomes the dominant channel. The rate
      constant calculated by RRKM theory agrees reasonably well with experimental data.

PMID- 18816043
TI  - A multinuclear solid-state NMR study of alkali metal ions in tetraphenylborate
      salts, M[BPh4] (M = Na, K, Rb and Cs): what is the NMR signature of cation-pi
      interactions?
AB  - We report a multinuclear solid-state ( (23)Na, (39)K, (87)Rb, (133)Cs) NMR study
      of tetraphenylborate salts, M[BPh 4] (M = Na, K, Rb, Cs). These compounds are
      isostructural in the solid state with the alkali metal ion surrounded by four
      phenyl groups resulting in strong cation-pi interactions. From analyses of solid
      state NMR spectra obtained under stationary and magic-angle spinning (MAS)
      conditions at 11.75 and 21.15 T, we have obtained the quadrupole coupling
      constants, C Q, and the chemical shift tensor parameters for the alkali metal
      ions in these compounds. We found that the observed quadrupole coupling constant
      for M (+) in M[BPh 4] is determined by a combination of nuclear quadrupole
      moment, Sternheimer antishielding factor, and unit cell dimensions. On the basis
      of a comparison between computed paramagnetic and diamagnetic contributions to
      the total chemical shielding values for commonly found cation-ligand
      interactions, we conclude that cation-pi interactions give rise to significantly
      lower paramagnetic shielding contributions than other cation-ligand interactions.
      As a result, highly negative chemical shifts are expected to be the NMR signature
      for cations interacting exclusively with pi systems.

PMID- 18816044
TI  - Thiophene bioisosteres of spirocyclic sigma receptor ligands. 1. N-substituted
      spiro[piperidine-4,4'-thieno[3,2-c]pyrans].
AB  - Herein, the synthesis and pharmacological evaluation of thiophene bioisosteres of
      the highly potent spirocyclic benzopyran 1 are detailed. The synthesis of 1
      benzyl-6'-methoxy-6',7'-dihydrospiro[piperidine-4,4'-thieno[3.2- c]pyran] (2a)
      was performed starting with 3-bromothiophene (3). After introduction of the
      acetaldehyde substructure (7), halogen metal exchange, addition of 1
      benzylpiperidin-4-one, and cyclization led to the spirocyclic thienopyran 2a. The
      removal of the benzyl group afforded the secondary amine 2f, which was
      substituted with various residues. With respect to sigma 1 affinity the N-benzyl
      derivative 2a, the N-cyclohexylmethyl derivative 2d, and the N-p-fluorobenzyl
      derivative 2i represent the most potent compounds of this series binding with K i
      values of 0.32, 0.29, and 0.62 nM, respectively. Electronic properties of the
      substituents have only little impact on sigma 1 affinity. The most potent sigma 1
      ligands display high selectivity against sigma 2, 5-HT 1A, 5-HT 6, 5-HT 7, alpha
      1A, alpha 2, and NMDA receptors. The activity of 2a in the mouse capsaicin assay
      seems to indicate sigma 1 antagonistic activity.

PMID- 18816045
TI  - Design and synthesis of a novel series of pyranonaphthoquinones as topoisomerase
      II catalytic inhibitors.
AB  - On the basis of previous pharmacophore modeling studies of naphthoquinones
      derivatives, we have designed and synthesized a new set of pyranonaphthoquinones.
      These compounds were obtained through a direct and highly efficient approach
      based on an intramolecular domino Knoevenagel hetero Diels-Alder reaction from
      lawsone (2-hydroxynaphthoquinone) and a variety of aldehydes containing an
      alkene. The synthesized pyranonaphthoquinones were evaluated against the alpha
      isoform of human topoisomerase II (hTopoIIalpha). Among the 11 derivatives
      studied, we found that six of them act as catalytic inhibitors of the enzyme in
      vitro. These six derivatives strongly preclude the enzyme from decatenating or
      relaxing suitable substrates. Finally, we correlate their active/inactive status
      with docking studies of these novel compounds into the ATPase domain of
      hTopoIIalpha.

PMID- 18816046
TI  - Fully automated molecular mechanics based induced fit protein-ligand docking
      method.
AB  - We describe a method for docking a ligand into a protein receptor while allowing
      flexibility of the protein binding site. The method employs a multistep procedure
      that begins with the generation of protein and ligand conformations. An initial
      placement of the ligand is then performed by computing binding site hotspots.
      This initial placement is followed by a protein side-chain refinement stage that
      models protein flexibility. The final step of the process is an energy
      minimization of the ligand pose in the presence of the rigid receptor. Thus the
      algorithm models flexibility of the protein at two stages, before and after
      ligand placement. We validated this method by performing docking and cross
      docking studies of eight protein systems for which crystal structures were
      available for at least two bound ligands. The resulting rmsd values of the 21
      docked protein-ligand complexes showed values of 2 A or less for all but one of
      the systems examined. The method has two critical benefits for high throughput
      virtual screening studies. First, no user intervention is required in the docking
      once the initial binding site selection has been made in the protein. Second, the
      initial protein conformation generation needs to be performed only once for a
      given binding region. Also, the method may be customized in various ways
      depending on the particular scenario in which dockings are being performed. Each
      of the individual steps of the method is fully independent making it
      straightforward to explore different variants of the high level workflow to
      further improve accuracy and performance.

PMID- 18816047
TI  - The layered thiostannate (dienH2)Cu2Sn2S6: a photoconductive inorganic-organic
      hybrid compound.
AB  - The new inorganic-organic hybrid compound (dienH2)Cu2Sn2S6 (dien =
      diethylenetriamine) was synthesized under solvothermal conditions. It
      crystallizes in the tetragonal space group I4m2 with a = 7.8793(3) A, c =
      24.9955(15) A, and V = 1551.80(13) A(3). The structure consists of anionic
      [Cu2Sn2S6](2-) layers extending in the (001) plane and protonated amine molecules
      as charge compensating ions sandwiched between the layers. The layered
      [Cu2Sn2S6](2-) anion is composed of a single layer of edge-sharing CuS4
      tetrahedra which is joined above and below to straight chains constructed by
      corner-sharing SnS4 tetrahedra. The material is a semiconductor with an optical
      band gap of 1.51 eV. More interestingly, preliminary results demonstrate that the
      compound exhibits photoconductive properties with an increase of the conductivity
      by a factor of 3 when irradiated with UV light. Upon heating in an inert
      atmosphere the compound starts to decompose at about 256 degrees C.

PMID- 18816048
TI  - Strong rail spin 1/2 antiferromagnetic ladder systems: (dimethylammonium)(3,5
      dimethylpyridinium)CuX4, X = Cl, Br.
AB  - The mixed cation salts, (dimethylammonium)(3,5-dimethylpyridinium)CuX4 (X = Cl,
      Br), henceforth (DMA)(35DMP)CuX4, are new examples of spin-ladders based on
      nonbonded halide...halide interactions between CuX4(2-) anions. In these
      structures, double rows of the CuX4(2-) anions are sheathed by the 35DMP(+)
      cations, while the edges are capped by the DMA(+) cations. For the Br salt, the
      Br...Br contacts that define the rungs of the ladder are 4.017 A in length, while
      those that define the rails are 3.983 A. For the Cl salt, the corresponding
      lengths are 3.967 and 4.045 A. The susceptibility data for the Br salt exhibits a
      maximum at approximately 5.5 K, and fitting the data to the spin 1/2
      antiferromagnetic ladder model yields 2J(rail)/k = -7.95 K and 2J(rung)/k = -4.07
      K. The exchange coupling is much weaker in the Cl salt, no maximum in chi is
      observed down to 1.8 K, and the corresponding exchange constants are -1.59 and 
      1.25 K, respectively. An analysis is made of the structural factors involved in
      the J(rung) pathway.

PMID- 18816049
TI  - Co(C2O4)(HO(CH2)3OH): an antiferromagnetic neutral zigzag chain compound showing
      long-range ordering of spin canting.
AB  - A centrosymmetric compound consisting of neutral zigzag chains of
      [Co(C2O4)(HO(CH2)3OH)]n displays strong intrachain antiferromagnetic interaction
      and 3D weak ferromagnetic ordering at 10.6 K.

PMID- 18816050
TI  - Cationic methyl complexes of the rare-earth metals: an experimental and
      computational study on synthesis, structure, and reactivity.
AB  - Synthesis, structure, and reactivity of two families of rare-earth metal
      complexes containing discrete methyl cations [LnMe(2-x)(thf)n]((1+x)+) (x = 0, 1;
      thf = tetrahydrofuran) have been studied. As a synthetic equivalent for the
      elusive trimethyl complex [LnMe3], lithium methylates of the approximate
      composition [Li3LnMe6(thf)n] were prepared by treating rare-earth metal
      trichlorides [LnCl3(thf)n] with 6 equiv of methyllithium in diethyl ether.
      Heteronuclear complexes of the formula [Li3Ln2Me9L(n)] (Ln = Sc, Y, Tb; L = Et2O,
      thf) were isolated by crystallization from diethyl ether. Single crystal X-ray
      diffraction studies revealed a heterometallic aggregate of composition
      [Li3Ln2Me9(thf)n(Et2O)m] with a [LiLn2Me9](2-) core (Ln = Sc, Y, Tb). When
      tris(tetramethylaluminate) [Ln(AlMe4)3] (Ln = Y, Lu) was reacted with less than 1
      equiv of [NR3H][BPh4], the dimethyl cations [LnMe2(thf)n][BPh4] were obtained.
      The coordination number as well as cis/trans isomer preference was studied by
      crystallographic and computational methods. Dicationic methyl complexes of the
      rare-earth metals of the formula [LnMe(thf)n][BAr4]2 (Ln = Sc, Y, La-Nd, Sm, Gd
      Lu; Ar = Ph, C6H4F-4) were synthesized, by protonolysis of either the ate complex
      [Li3LnMe6(thf)n] (Ln = Sc, Y, Gd-Lu) or the tris(tetramethylaluminate)
      [Ln(AlMe4)3] (Ln = La-Nd, Sm, Dy, Gd) with ammonium borates [NR3H][BAr4] in thf.
      The number of coordinated thf ligands varied from n = 5 (Ln = Sc, Tm) to n = 6
      (Ln = La, Y, Sm, Dy, Ho). The configuration of representative examples was
      determined by X-ray diffraction studies and confirmed by density-functional
      theory calculations. The highly polarized bonding between the methyl group and
      the rare-earth metal center results in the reactivity pattern dominated by the
      carbanionic character and the pronounced Lewis acidity: The dicationic methyl
      complex [YMe(thf)6](2+) inserted benzophenone as an electrophile to give the
      alkoxy complex [Y(OCMePh2)(thf)5](2+). Nucleophilic addition of the soft anion X(
      ) (X(-) = I(-), BH4(-)) led to the monocationic methyl complexes
      [YMe(X)(thf)5](+).

PMID- 18816053
TI  - How the pi conjugation length affects the fluorescence emission efficiency.
AB  - How the pi conjugation length affects the fluorescence emission efficiency is
      elucidated by examination of the theoretical and experimental relationship
      between absolute quantum yield (Phi(f)) and magnitude (Api) of the pi conjugation
      length in the excited singlet state, which provides a novel concept for molecular
      design for highly fluorescent organic compounds. As a tool to predict Phi(f) from
      a structural model, (nu(a) - nu(f))1/2 x a3/2 (nu(a): wavenumber of absorption
      maximum, nu(f): wavenumber of emission maximum, a: molecular radius) could be
      used instead of Api. The concept should be valuable for potential applications to
      (1) examination of an excited singlet state structure (for example, coplanarity
      of excited-state molecules) and (2) molecular design of novel materials, in which
      the excited singlet state plays an important role, such as highly efficient
      fluorophores, electroluminescent materials, photoconducting materials, and
      nonlinear optical materials. A remarkably intense green fluorophore (Phi(f) 0.88,
      log epsilon 4.72, lambda(em) 527 nm) is created based on this concept, which is
      of great interest in relation to a green fluorescent protein (Topaz, T203Y type,
      Phi(f) 0.60, log epsilon 4.98, lambda(em) 527 nm).

PMID- 18816054
TI  - Glycine exists mainly as monomers, not dimers, in supersaturated aqueous
      solutions: implications for understanding its crystallization and polymorphism.
AB  - Glycine, the simplest amino acid, is described as existing as hydrogen-bonded
      cyclic dimers in supersaturated aqueous solutions and, as a result, crystallizing
      in a centrosymmetric polymorph (polymorph alpha) for which the dimer can be
      viewed as the building unit, in favor of other polymorphs of polar structures. In
      exhibiting this relation between polymorphic selectivity and self-association in
      solution, glycine is thought to illustrate a general principle. We measured the
      freezing-point depression of glycine-water up to 30% supersaturation and found
      that glycine exists mainly as monomers, not dimers, and that the dimer stability
      constant K D is smaller than 0.1 kg of H 2O/mol if the observed osmotic
      abnormality is attributed to dimerization. We also revisited a report cited as
      evidence for glycine dimerization: the slowdown of glycine diffusion with
      solution age. Pulsed gradient spin-echo NMR spectroscopy was used in place of the
      previous method of Gouy interferometry to avoid perturbations to sloution
      structure caused by the interdiffusion between two solutions of different
      concentrations. No aging effect was observed on glycine diffusion up to 24%
      supersaturation after five days. The solute size calculated from diffusivity,
      viscosity, and the Stokes-Einstein relation showed no increase with concentration
      or solution age. We conclude that glycine exists in supersaturated aqueous
      solutions mainly as monomers, not dimers, and remains so upon aging. This result
      does not invalidate the theories of how pH and additives affect glycine's
      polymorphic preference, because they begin with the assumption that alpha glycine
      is the preferred polymorph under normal conditions, but requires a new
      explanation for that assumption itself.

PMID- 18816055
TI  - Tetrazoles are potent anion recognition elements that emulate the disfavored anti
      conformations of carboxylic acids.
AB  - We report here the first study of the protonated, neutral form of tetrazoles as
      anion binding functional groups. Our studies reveal them to be capable of binding
      anions with extremely high potency in polar solutions. In studying carboxylic
      acid-containing congeners, we find a remarkable discrepancy: a strictly analogous
      acid-containing host binds anions > or = 50,000-fold more weakly than the
      tetrazole under study. We can explain this functional difference by considering
      tetrazole tautomerization equilibria and carboxylic acid conformational
      preferences.

PMID- 18816056
TI  - Changes in free amino acid and sugar levels of dried figs during aflatoxin B1
      production by Aspergillus flavus and Aspergillus parasiticus.
AB  - An aqueous slurry of gamma-irradiated sterilized dried figs was inoculated with
      toxigenic strains of Aspergillus flavus and Aspergillus parasiticus. During
      incubation at 28 degrees C, pH, fructose, glucose, and free amino acids were
      determined by high-performance liquid chromatography and liquid chromatography
      (LC)/mass spectrometry, respectively, over 13 time points (1-20 days). At the
      same 13 time points using a LC/time-of-flight mass spectrometry screening method,
      aflatoxin B 1 and other secondary metabolites were simultaneously monitored.
      During the course of incubation, the pH significantly decreased and aflatoxin B 1
      formation correlated with a reduction in proline content for both fungi. Of the
      22 free amino acids that were monitored, only proline and cystine were found to
      be critical in supporting aflatoxin production. Levels of fructose and glucose
      steadily declined during incubation, until glucose was almost exhausted after 21
      days. These time-course experiments confirmed the need for carbon and nitrogen
      sources for aflatoxin production in dried figs, and the favorable composition of
      figs as a fungal growth medium.

PMID- 18816057
TI  - Treatment with taurine attenuates hepatic apoptosis in NZB/W F1 mice fed with a
      high-cholesterol diet.
AB  - Cholesterol-rich diets are known to cause hepatic apoptosis, which has been
      associated with the pathogenesis of systemic lupus erythematosus (SLE). However,
      the mechanisms and treatments for hepatic apoptosis in SLE are poorly understood.
      To clarify the effects of taurine on hepatic apoptosis in SLE, NZB/W F1 mice
      received control, cholesterol, and cholesterol/taurine diets. Significant
      reductions of caspase-3 activity, TUNEL-positive cells, and Fas- and
      mitochondrial- dependent apoptosis were detected in liver from the
      cholesterol/taurine group as compared to the cholesterol group. Moreover,
      significant increases of phosphorylated AKT, NF-kappaB (p65), and ERK1/2 proteins
      were detected in liver from the cholesterol/taurine group as compared to the
      cholesterol group. In contrast, a significant reduction of phosphorylated p38
      protein was observed in the cholesterol/taurine group. These experimental results
      demonstrated positive effects of taurine against hepatic apoptosis in NZB/W F1
      mice fed a high-cholesterol diet and suggested the therapeutic potential of
      taurine in SLE.

PMID- 18816058
TI  - Strawberry extract caused endothelium-dependent relaxation through the activation
      of PI3 kinase/Akt.
AB  - Polyphenolic compounds are vasodilators and help to lower the risk of
      cardiovascular diseases. We hypothesized that a freeze-dried strawberry powder
      that is rich in polyphenolic compounds would cause an endothelium-dependent
      relaxation (EDR) through the activation of phosphatidylinositol-3 (PI3)
      kinase/protein kinase B (Akt) in rabbit aorta. The powder was prepared by freeze
      drying a homogenate of ripe California strawberry fruits. An aqueous extract of
      strawberry powder was applied to rabbit aortic rings suspended in organ baths
      containing Krebs-Henseleit buffer maintained at 37 degrees C. In aortic rings
      precontacted with norepinephrine, the extract produced a dose-dependent
      relaxation. The maximum relaxations elicited by the extract (73.1 +/- 1.0%) were
      similar to those elicited by acetylcholine (68.2 +/- 1.5%) ( n = 14 for each).
      The relaxation by strawberry extract was abolished by removal of the endothelium
      and by prior incubation with N omega-nitro- l-arginine methyl ester hydrochloride
      (L-NAME), confirming the essential role of endothelial nitric oxide synthase
      (eNOS). The responses to the strawberry were also abolished by incubation with
      wortmannin and LY294002, which are inhibitors of PI3 kinase. Using
      immunoblotting, we also demonstrated that the strawberry extract induced the
      phosphorylation of both Akt and eNOS in human umbilical vein endothelial cells
      (HUVECs) via PI3 kinase/Akt pathway. Taken together, our novel findings suggest
      that the EDR induced by the strawberry extract was mediated by activation of the
      PI3 kinase/Akt signaling pathway, resulting in phosphorylation of eNOS.

PMID- 18816059
TI  - Batatinosides II-VI, acylated lipooligosaccharides from the resin glycosides of
      sweet potato.
AB  - Sweet potato ( Ipomoea batatas) belongs to the Convolvulaceae (morning glory
      family) and is native to Mexico and Central America. Its edible tuberous roots
      have been much appreciated since pre-Hispanic times in Mesoamerica and now play
      an important role as a basic diet staple and a medicinal plant worldwide. The
      hexane-soluble extract from roots, through preparative-scale recycling HPLC,
      yielded five new lipophilic oligosaccharides of jalapinolic acid, batatinosides
      II-VI ( 1- 5), as well as the known pescapreins I ( 6) and VII ( 7) and
      murucoidin I ( 8), which are part of the purgative resin glycoside mixture. NMR
      spectroscopy and FAB mass spectrometry were used to characterize their
      structures. Compounds 1 and 2 are tetraglycosidic lactones of operculinic acid C.
      The pentasaccharide structures for compounds 3 and 4 were confirmed to be
      macrolactones of simonic acid B, and that characterized for 5 was derived from
      operculinic acid A. The lactonization site of the aglycone was placed at C-3 of
      the second saccharide unit in all compounds except 4, where it was placed at C-2.
      All compounds contain an esterifying residue that is composed of a long-chain
      fatty acid, n-decanoic acid (capric) or n-dodecanoic acid (lauric). In compound
      3, an additional short-chain fatty acid, (2 S)-methylbutyric acid, was also
      identified.

PMID- 18816060
TI  - Anti-inflammatory activity of an orange peel polymethoxylated flavone,
      3',4',3,5,6,7,8-heptamethoxyflavone, in the rat carrageenan/paw edema and mouse
      lipopolysaccharide-challenge assays.
AB  - The anti-inflammatory properties of 3',4',3,5,6,7,8-heptamethoxyflavone (HMF), a
      citrus polymethoxylated flavone, were studied in the bacterial lipopolysaccharide
      (LPS)-challenge/tumor necrosis factor-alpha (TNFalpha) response in mice and in
      the carrageenan/paw edema assay in rats. In each of these trials, HMF
      administered by intraperitoneal (ip) injection exhibited anti-inflammatory
      activity, whereas HMF administered orally (po) produced no effects. The
      inhibition observed in the LPS-challenge/TNFalpha assay correlated with the HMF
      levels in the blood sera of mice dosed (ip) with either 33 or 100 mg/kg body
      weight. Low levels of HMF (0.035 +/- 0.024 ppm) were detected in the blood sera
      of mice dosed orally [100 mg of HMF (suspended in vegetable oil)/kg], whereas ip
      injection led to higher levels (0.517 +/- 0.051 ppm). This may account for the
      different levels of anti-inflammatory effects observed in mice following ip vs
      oral HMF administration. HMF metabolites, including a number of mono- and di
      demethylated HMF metabolites and their glucuronic acid conjugates, were also
      detected, but results of these studies suggest that the glucuronidated
      metabolites of HMF are inactive in these inflammation models.

PMID- 18816061
TI  - Effect of heating oxymyoglobin and metmyoglobin on the oxidation of muscle
      microsomes.
AB  - Myoglobin (Mb) and its iron have been proposed to be major prooxidants in cooked
      meats. To understand the mechanisms and differentiate between the prooxidant and
      antioxidant potential of oxymyoglobin (OxyMb) and metmyoglobin (MetMb), their
      prooxidant activity, iron content, solubility, free radical scavenging activity,
      and iron binding capacity were determined as a function of thermal processing.
      The ability of native and heat denatured OxyMb and MetMb to promote the oxidation
      of muscle microsomes was different. MetMb promoted lipid oxidation in both its
      native and denatured states. Conversely, OxyMb became antioxidative when the
      protein was heated to temperatures >or=75 degrees C. The increased antioxidant
      activity of heat denatured OxyMb was likely due to a decrease in its prooxidative
      activity due to its loss of solubility. These data show that the impact on
      oxidative reactions of Mb is the result of the balance between its antioxidant
      and prooxidant activities.

PMID- 18816062
TI  - Engineering a camelid antibody fragment that binds to the active site of human
      lysozyme and inhibits its conversion into amyloid fibrils.
AB  - A single-domain fragment, cAb-HuL22, of a camelid heavy-chain antibody specific
      for the active site of human lysozyme has been generated, and its effects on the
      properties of the I56T and D67H amyloidogenic variants of human lysozyme, which
      are associated with a form of systemic amyloidosis, have been investigated by a
      wide range of biophysical techniques. Pulse-labeling hydrogen-deuterium exchange
      experiments monitored by mass spectrometry reveal that binding of the antibody
      fragment strongly inhibits the locally cooperative unfolding of the I56T and D67H
      variants and restores their global cooperativity to that characteristic of the
      wild-type protein. The antibody fragment was, however, not stable enough under
      the conditions used to explore its ability to perturb the aggregation behavior of
      the lysozyme amyloidogenic variants. We therefore engineered a more stable
      version of cAb-HuL22 by adding a disulfide bridge between the two beta-sheets in
      the hydrophobic core of the protein. The binding of this engineered antibody
      fragment to the amyloidogenic variants of lysozyme inhibited their aggregation
      into fibrils. These findings support the premise that the reduction in global
      cooperativity caused by the pathogenic mutations in the lysozyme gene is the
      determining feature underlying their amyloidogenicity. These observations
      indicate further that molecular targeting of enzyme active sites, and of protein
      binding sites in general, is an effective strategy for inhibiting or preventing
      the aberrant self-assembly process that is often a consequence of protein
      mutation and the origin of pathogenicity. Moreover, this work further
      demonstrates the unique properties of camelid single-domain antibody fragments as
      structural probes for studying the mechanism of aggregation and as potential
      inhibitors of fibril formation.

PMID- 18816063
TI  - Using an amino acid fluorescence resonance energy transfer pair to probe protein
      unfolding: application to the villin headpiece subdomain and the LysM domain.
AB  - Previously, we have shown that p-cyanophenylalanine (Phe CN) and tryptophan (Trp)
      constitute an efficient fluorescence resonance energy transfer (FRET) pair that
      has several advantages over commonly used dye pairs. Here, we aim to examine the
      general applicability of this FRET pair in protein folding-unfolding studies by
      applying it to the urea-induced unfolding transitions of two small proteins, the
      villin headpiece subdomain (HP35) and the lysin motif (LysM) domain. Depending on
      whether Phe CN is exposed to solvent, we are able to extract either qualitative
      information about the folding pathway, as demonstrated by HP35, which has been
      suggested to unfold in a stepwise manner, or quantitative thermodynamic and
      structural information, as demonstrated by LysM, which has been shown to be an
      ideal two-state folder. Our results show that the unfolding transition of HP35
      reported by FRET occurs at a denaturant concentration lower than that measured by
      circular dichroism (CD) and that the loop linking helix 2 and helix 3 remains
      compact in the denatured state, which are consistent with the notion that HP35
      unfolds in discrete steps and that its unfolded state contains residual
      structures. On the other hand, our FRET results on the LysM domain allow us to
      develop a model for extracting structural and thermodynamic parameters about its
      unfolding, and we find that our results are in agreement with those obtained by
      other methods. Given the fact that Phe CN is a non-natural amino acid and, thus,
      amenable to incorporation into peptides and proteins via existing peptide
      synthesis and protein expression methods, we believe that the FRET method
      demonstrated here is widely applicable to protein conformational studies,
      especially to the study of relatively small proteins.

PMID- 18816064
TI  - The ClpP N-terminus coordinates substrate access with protease active site
      reactivity.
AB  - Energy-dependent protein degradation machines, such as the Escherichia coli
      protease ClpAP, require regulated interactions between the ATPase component
      (ClpA) and the protease component (ClpP) for function. Recent studies indicate
      that the ClpP N-terminus is essential in these interactions, yet the dynamics of
      this region remain unclear. Here, we use synchrotron hydroxyl radical
      footprinting and kinetic studies to characterize functionally important
      conformational changes of the ClpP N-terminus. Footprinting experiments show that
      the ClpP N-terminus becomes more solvent-exposed upon interaction with ClpA. In
      the absence of ClpA, deletion of the ClpP N-terminus increases the initial
      degradation rate of large peptide substrates 5-15-fold. Unlike ClpAP, ClpPDeltaN
      exhibits a distinct slow phase of product formation that is eliminated by the
      addition of hydroxylamine, suggesting that truncation of the N-terminus leads to
      stabilization of the acyl-enzyme intermediate. These results indicate that (1)
      the ClpP N-terminus acts as a "gate" controlling substrate access to the active
      sites, (2) binding of ClpA opens this "gate", allowing substrate entry and
      formation of the acyl-enzyme intermediate, and (3) closing of the N-terminal
      "gate" stimulates acyl-enzyme hydrolysis.

PMID- 18816065
TI  - Kinetic and mechanistic characterization and versatile catalytic properties of
      mammalian glutaredoxin 2: implications for intracellular roles.
AB  - Glutaredoxin (Grx)-catalyzed deglutathionylation of protein-glutathione mixed
      disulfides (protein-SSG) serves important roles in redox homeostasis and signal
      transduction, regulating diverse physiological and pathophysiological events.
      Mammalian cells have two Grx isoforms: Grx1, localized to the cytosol and
      mitochondrial intermembrane space, and Grx2, localized primarily to the
      mitochondrial matrix [Pai, H. V., et al. (2007) Antioxid. Redox Signaling 9, 2027
      2033]. The catalytic behavior of Grx1 has been characterized extensively, whereas
      Grx2 catalysis is less well understood. We observed that human Grx1 and Grx2
      exhibit key catalytic similarities, including selectivity for protein-SSG
      substrates and a nucleophilic, double-displacement, monothiol mechanism
      exhibiting a strong commitment to catalysis. A key distinction between Grx1- and
      Grx2-mediated deglutathionylation is decreased catalytic efficiency ( k cat/ K M)
      of Grx2 for protein deglutathionylation (due primarily to a decreased k cat),
      reflecting a higher p K a of its catalytic cysteine, as well as a decreased
      enhancement of nucleophilicity of the second substrate, GSH. As documented
      previously for hGrx1 [Starke, D. W., et al. (2003) J. Biol. Chem. 278, 14607
      14613], hGrx2 catalyzes glutathione-thiyl radical (GS (*)) scavenging, and it
      also mediates GS transfer (protein S-glutathionylation) reactions, where GS (*)
      serves as a superior glutathionyl donor substrate for formation of GAPDH-SSG,
      compared to GSNO and GSSG. In contrast to its lower k cat for deglutathionylation
      reactions, Grx2 promotes GS-transfer to the model protein substrate GAPDH at
      rates equivalent to those of Grx1. Estimation of Grx1 and Grx2 concentrations
      within mitochondria predicts comparable deglutathionylation activities within the
      mitochondrial subcompartments, suggesting localized regulatory functions for both
      isozymes.

PMID- 18816066
TI  - Structural and thermodynamic characterization of T4 lysozyme mutants and the
      contribution of internal cavities to pressure denaturation.
AB  - Using small-angle X-ray scattering (SAXS) and tryptophan fluorescence
      spectroscopy, we have identified multiple compact denatured states of a series of
      T4 lysozyme mutants that are stabilized by high pressures. Recent studies imply
      that the mechanism of pressure denaturation is the penetration of water into the
      protein rather than the transfer of hydrophobic residues into water. To
      investigate water penetration and the volume change associated with pressure
      denaturation, we studied the solution behavior of four T4 lysozyme mutants having
      different cavity volumes at low and neutral pH up to a pressure of 400 MPa (0.1
      MPa = 0.9869 atm). At low pH, L99A T4 lysozyme expanded from a compact folded
      state to a partially unfolded state with a corresponding change in radius of
      gyration from 17 to 32 A. The volume change upon denaturation correlated well
      with the total cavity volume, indicating that all of the molecule's major
      cavities are hydrated with pressure. As a direct comparison to high-pressure
      crystal structures of L99A T4 lysozyme solved at neutral pH [Collins, M. D.,
      Hummer, G., Quillin, M. L., Matthews, B. W., and Gruner, S. M. (2005) Proc. Natl.
      Acad. Sci. U.S.A. 102, 16668-16671], pressure denaturation of L99A and the
      structurally similar L99G/E108V mutant was studied at neutral pH. The pressure
      denatured state at neutral pH is even more compact than at low pH, and the small
      volume changes associated with denaturation suggest that the preferential filling
      of large cavities is responsible for the compactness of the pressure-denatured
      state. These results confirm that pressure denaturation is characteristically
      distinct from thermal or chemical denaturation.

PMID- 18816067
TI  - In situ amplified electrochemical immunoassay for carcinoembryonic antigen using
      horseradish peroxidase-encapsulated nanogold hollow microspheres as labels.
AB  - Methods based on sandwich-type electrochemical enzyme immunoassay protocol have
      been extensively developed for the detection of biomolecules, but most often
      exhibit low detection signals and low detection sensitivity, and are unsuitable
      for routine use. In this study, we initially synthesized specially horseradish
      peroxidase-encapsulated nanogold hollow microspheres (HRP-GHS), and then the
      prepared HRP-GHS was conjugated to the secondary carcinoembryonic antibody (HRP
      GHS- anti-CEA). Carcinoembryonic antigen (CEA), as a model protein, was monitored
      by using the electrochemical sandwich-type enzyme immunoassay format. Under
      optimized conditions, the linear range of the immunoassay by using single HRP
      labeled anti-CEA (HRP- anti-CEA) as secondary antibodies is 2.5-120 ng/mL with a
      detection limit of 1.5 ng/mL CEA, while the assay sensitivity by using HRP-GHS-
      anti-CEA as secondary antibodies is further increased from 0.01 to 200 ng/mL with
      a lower detection limit of 1.5 pg/mL CEA. The intra- and interassay
      reproducibility is acceptable. The CEA concentrations of the clinical serum
      specimens assayed by the developed immunoassay show consistent results in
      comparison with those obtained by commercially available enzyme-linked
      immunosorbent assay. This immunoassay system has many desirable merits including
      sensitivity, accuracy, and little required instrumentation. Significantly, the
      new protocol may be quite promising, with potentially broad applications for
      clinical immunoassays.

PMID- 18816068
TI  - Electrochemical biosensor for detection of BCR/ABL fusion gene using locked
      nucleic acids on 4-aminobenzenesulfonic acid-modified glassy carbon electrode.
AB  - In this study, an electrochemical DNA biosensor was developed for detection of
      the breakpoint cluster region gene and the cellular abl (BCR/ABL) fusion gene in
      chronic myelogenous leukemia by using 18-mer locked, nucleic acid-modified,
      single-stranded DNA as the capture probe. The capture probe was covalently
      attached on the sulfonic-terminated aminobenzenesulfonic acid monolayer-modified
      glassy carbon electrode through the free amines of DNA bases based on the acyl
      chloride cross-linking reaction. The covalently immobilized capture probe could
      selectively hybridize with its target DNA to form double-stranded DNA (dsDNA) on
      the LNA/4-ABSA/GCE surface. Differential pulse voltammetry was used to monitor
      the hybridization reaction on the capture probe electrode. The decrease of the
      peak current of methylene blue, an electroactive indicator, was observed upon
      hybridization of the probe with the target DNA. The results indicated that, in pH
      7.0 Tris-HCl buffer solution, the peak current was linear with the concentration
      of complementary strand in the range of 1.0 x 10 (-12)1.1 x 10 (-11) M with a
      detection limit of 9.4 x 10 (-13) M. This new method demonstrates its excellent
      specificity for single-base mismatch and complementary dsDNA after hybridization,
      and this probe has been used for assay of PCR real sample with satisfactory
      results.

PMID- 18816069
TI  - A fundamental study on electrowetting by traditional and multifunctional ionic
      liquids: possible use in electrowetting on dielectric-based microfluidic
      applications.
AB  - Water or aqueous electrolytes are the dominant components in electrowetting on
      dielectric (EWOD)-based microfluidic devices. Low thermal stability, evaporation,
      and a propensity to facilitate corrosion of the metal parts of integrated
      circuits or electronics are drawbacks of aqueous solutions. The alternative use
      of ionic liquids (ILs) as electrowetting agents in EWOD-based applications or
      devices could overcome these limitations. Efficient EWOD devices could be
      developed using task-specific ILs. In this regard, a fundamental study on the
      electrowetting properties of ILs is essential. Therefore electrowetting
      properties of 19 different ionic liquids, including mono-, di-, and tricationic,
      plus mono- and dianionic ILs were examined. All tested ILs showed electrowetting
      of various magnitudes on an amorphous flouropolymer layer. The effects of IL
      structure, functionality, and charge density on the electrowetting properties
      were studied. The enhanced stability of ILs in electrowetting on dielectric at
      higher voltages was studied in comparison with water. Deviations from classical
      electrowetting theory were confirmed. The physical properties of ILs and their
      electrowetting properties were tabulated. These data can be used as references to
      engineer task-specific electrowetting agents (ILs) for future electrowetting
      based applications.

PMID- 18816070
TI  - In situ determination of bacterial growth by multiple headspace extraction gas
      chromatography.
AB  - This paper demonstrated an in situ headspace gas chromatography (GC) technique
      for monitoring bacterial growth using a commercial GC system with a multiple
      headspace extraction (sampling) mode. The technique was based on measuring the
      carbon dioxide mass in the headspace of a closed sample vial during the bacteria
      growth. A mathematic equation was derived in order to calculate the integrated
      amount of carbon dioxide produced by bacterial growth during the incubation. The
      method can be used to monitor the bacterial growth rate in a given cultural
      medium. The present method is very simple, sensitive, and safe.

PMID- 18816071
TI  - Kinetics of antigen-antibody interactions employing a MALDI mass spectrometry
      immunoassay.
AB  - Time-course MALDI mass spectrometry immunoassays have been shown to be able to
      detect differences in the relative rates of binding of peptides, both from within
      and across epitopic domains, with antibodies in non-competitive and competitive
      experiments. A monoclonal antibody raised to target the HA1 subunit of the
      hemagglutinin antigen of type A H3N2 influenza strains is found to recognize two
      epitopic peptides comprising residues 109-125 and 158-166 that likely form part
      of an extended discontinuous domain. Time-course experiments show the smaller
      peptide binds antibody at a rate that is 5-fold faster than that for the larger
      peptide. A shorter segment of this larger peptide, comprised of residues 119-125,
      is also found to bind at twice the rate of the extended peptide. Studies of
      modified peptide variants and synthetic variants of HA peptide 119-125 has
      enabled important contact residues to be identified whose accessibilities in the
      native protein are in accord with the mass spectrometry results.

PMID- 18816072
TI  - Probing inhibitory effects of Antrodia camphorata isolates using insect cell
      based impedance spectroscopy: inhibition vs chemical structure.
AB  - A continuous online technique based on electric cell-substrate impedance sensing
      (ECIS) was used for probing inhibitory effects on Spodoptera frugiperda Sf9
      insect cells exposed to structurally similar compounds isolated and purified from
      the fruiting bodies of the fungus Antrodia camphorata. Such chemicals consisted
      of three ergostane-related steroids and five lanosta-related triterpenes, which
      are known for their diverse properties and use in the formulation of
      nutraceuticals and functional foods. The half-inhibition concentration
      (ECIS(50)), the level at which 50% inhibition of the resistance response was
      obtained, was determined from the response function to establish inhibitory
      effects of the different isolates. A slight change in their chemical structures
      resulted in significant effects on inhibition as probed by impedance
      spectroscopy. The ergostane-related steroids were mostly inhibitory, but
      replacing their ketone groups with hydrogen or hydroxyl groups significantly
      reduced the inhibition. Similarly, the addition of methyl or carboxymethyl groups
      also lowered the inhibition. Removal of the double bond conjugation within the
      rings (sulfurenic acid) of the isolate drastically reduced the inhibition.

PMID- 18816073
TI  - Theoretical and experimental studies of tyrosyl hydroperoxide formation in the
      presence of H-bond donors.
AB  - Oxidative damage to biomolecules such as lipids, proteins, nucleotides, and
      sugars has been implicated in the pathogenesis of various diseases. Superoxide
      radical anion (O 2 (*-)) addition to nitrones bearing an amide N-H has been shown
      to be more favored as compared to other nitrones [ Villamena, F. A. , ( 2007) J.
      Am. Chem. Soc. 129, 8177- 8191 ]. It has also been demonstrated by others [
      Winterbourn, C. C. , ( 2004) Biochem. J. 381, 241- 248 ] that O 2 (*-) addition
      to tyrosine to form hydroperoxide is favored in the presence of basic amino
      groups, but the mechanism for this observation remains obscure. We, therefore,
      hypothesized that the alpha-effect resulting from the interaction of O 2 (*-)
      with N-H can play a crucial role in the enhancement of hydroperoxide formation.
      Understanding this phenomenon is important in the elucidation of mechanisms
      leading to oxidative stress in cellular systems. Computational (at the
      PCM/B3LYP/6-31+G**//B3LYP/6-31G level of theory) as well as experimental studies
      were carried out to shed insights into the effect of amide or amino N-H on the
      enhancement (or stabilization) of hydroperoxide formation in tyrosine. H-bond
      interaction of amino acid group with O 2 (*-) results in the perturbation of the
      spin and charge densities of O 2 (*-). A similar phenomenon has been predicted
      for non-amino acids bearing H-bond donor groups. Using the FOX assay, tyrosyl
      hydroperoxide formation was enhanced in the presence of H-bond donors from amino
      acids and non-amino acids. The role of H-bonding in either stabilizing the
      hydroperoxide adduct or facilitating O 2 (*-) addition via an alpha-effect was
      further theoretically investigated, and results show that the latter mechanism is
      more thermodynamically preferred. This study provides new mechanistic insights in
      the initiation of oxidative modification to tyrosyl radical.

PMID- 18816074
TI  - Chemical forms of mercury and selenium in fish following digestion with simulated
      gastric fluid.
AB  - Fish is a major dietary source of potentially neurotoxic methylmercury compounds
      for humans. It is also a rich source of essential selenium. We have used in situ
      mercury L(III)-edge and selenium K-edge X-ray absorption spectroscopy to
      chemically characterize the methylmercury and selenium in both fresh fish and
      fish digested with simulated gastric fluid. For the mercury, we confirm our
      earlier finding [ Harris et al. ( 2003 ) Science 301 , 1203 ] that the
      methylmercury is coordinated by a single thiolate donor, which resembles
      cysteine, and for the selenium, we find a mixture of organic forms that resemble
      selenomethionine and an aliphatic selenenyl sulfide such as Cys-S-Se-Cys. We find
      that local chemical environments of mercury and selenium do not change upon
      digestion of the fish with simulated gastric fluid. We discuss the toxicological
      implications for humans consuming fish.

PMID- 18816075
TI  - Trimethoprim: novel reactive intermediates and bioactivation pathways by
      cytochrome p450s.
AB  - Trimethoprim (TMP) is a widely used antibacterial agent that is usually
      considered as a safe drug. TMP has, however, been implicated in rare adverse drug
      reactions (ADRs) in humans. Bioactivation to a reactive iminoquinone methide
      intermediate has been proposed as a possible cause for the toxicity of the drug.
      However, little is known about the cytochrome P450s (P450s) involved in this
      bioactivation and in the metabolism of TMP in general. In this study, we have
      investigated the metabolism and bioactivation of TMP by human liver microsomes
      (HLM) and rat liver microsomes, by recombinant human cytochrome P450s, and by the
      bacterial P450 BM3 mutant M11(his). In addition to non GSH-dependent metabolites,
      five GSH adducts were identified in the HLM incubations. Next to two major GSH
      adducts probably originating from the iminoquinone methide intermediate described
      previously, three minor GSH adducts were also identified, indicating that other
      types of reactive intermediates are formed by HLM, such as ortho-quinones and
      para-quinone methide intermediates. The major GSH adducts were produced by P450
      1A2 and P450 3A4, while the minor GSH adducts were mainly formed by P450 1A2,
      P450 3A4, and P450 2D6. Although preliminary, these results might implicate that
      genetic polymorphisms in P450 enzymes could play a role in the onset of TMP
      related ADRs in humans.

PMID- 18816076
TI  - Microfluidic synthesis and catalytic application of PVP-stabilized, approximately
      1 nm gold clusters.
AB  - Small PVP-stabilized gold clusters were successfully prepared by the homogeneous
      mixing of continuous flows of aqueous AuCl 4 (-) and BH 4 (-) in a micromixer.
      Spectroscopic characterization revealed that microfluidic synthesis could yield
      monodisperse Au:PVP clusters with an average diameter of approximately 1 nm,
      which is smaller than clusters produced by conventional batch methods. These
      approximately 1 nm Au:PVP clusters exhibited higher catalytic activity for the
      aerobic oxidation of p-hydroxybenzyl alcohol than did Au:PVP clusters prepared by
      batch methods.

PMID- 18816077
TI  - Probing fibronectin-surface interactions: a multitechnique approach.
AB  - The development of adhesive as well as antiadhesive surfaces is essential in
      various biomaterial applications. In this study, we have used a multidisciplinary
      approach that combines biological and physicochemical methods to progress in our
      understanding of cell-surface interactions. Four model surfaces have been used to
      investigate fibronectin (Fn) adsorption and the subsequent morphology and
      adhesion of preosteoblasts. Such experimental conditions lead us to distinguish
      between anti- and proadhesive substrata. Our results indicate that Fn is not able
      to induce cell adhesion on antiadhesive materials. On adhesive substrata, Fn did
      not increase the number of adherent cells but favored their spreading. This work
      also examined Fn-surface interactions using ELISA immunoassays, fluorescent
      labeling of Fn, and force spectroscopy with Fn-modified tips. The results
      provided clear evidence of the advantages and limitations of each technique. All
      of the techniques confirmed the important adsorption of Fn on proadhesive
      surfaces for cells. By contrast, antiadhesive substrata for cells avoided Fn
      adsorption. Furthermore, ELISA experiments enabled us to verify the accessibility
      of cell binding sites to adsorbed Fn molecules.

PMID- 18816079
TI  - Thermal stability and structural characterization of organic/inorganic hybrid
      nonlinear optical material containing a two-dimensional chromophore.
AB  - In this study, two nonlinear optic hybrid materials with different dimensional
      alkoxysilane dyes were prepared and characterized. One NLO silane (Cz2PhSO 2OH-
      TES), a two-dimensional structure based on carbazole, had a larger rotational
      volume than the other (DR19-TES). Second harmonic ( d 33) analysis verified there
      is an optimum heating process for the best poling efficiency. The maximum d 33
      value of NLO hybrid film containing Cz2PhSO 2OH was obtained for 10.7 pm/V after
      precuring at 150 degrees C for 3 h and poling at 210 degrees C for 60 min. The
      solid-state (29)Si NMR spectrum shows that the main factor influencing poling
      efficiency and thermal stability was cross-linking degree of NLO silane, but not
      that of TMOS. In particular, the two-dimensional sol-gel system has a greater
      dynamic and temporary stability than the one-dimensional system due to Cz2PhSO
      2OH-TES requiring a larger volume to rotate in the hybrid matrix after cross
      linking.

PMID- 18816080
TI  - Cell adhesion to nanoligands: effects of ligand size and concentration in
      solution.
AB  - Cells interact with both tethered and motile ligands in their extracellular
      environment to initiate and regulate signaling, adhesion, and migration. A
      quantitative and fundamental understanding of these receptor-ligand interactions
      is necessary for drug discovery, tissue engineering, and biomaterial fabrication.
      In this paper, we present a mean field approach to quantify the fundamental
      thermodynamics of interaction between the cell surface receptors and motile
      ligands in solvent. Our studies show that the free energy of interaction between
      the receptors and the nanosized ligands depends strongly on the ligand size and
      the effects at lower and higher concentrations show completely opposite trends
      that cannot be explained by simple scaling laws. In addition, we also observe
      various regimes of strong and weak adhesion as a function of ligand size and
      concentration. Our calculations provide insights into understanding cell-matrix
      interactions at a fundamental level as well as to identify potential avenues for
      fabrication of nanoligands for therapeutic and biotechnological purposes.

PMID- 18816081
TI  - Shotgun proteomics of the haloarchaeon Haloferax volcanii.
AB  - Haloferax volcanii, an extreme halophile originally isolated from the Dead Sea,
      is used worldwide as a model organism for furthering our understanding of
      archaeal cell physiology. In this study, a combination of approaches was used to
      identify a total of 1296 proteins, representing 32% of the theoretical proteome
      of this haloarchaeon. This included separation of (phospho)proteins/peptides by 2
      dimensional gel electrophoresis (2-D), immobilized metal affinity chromatography
      (IMAC), metal oxide affinity chromatography (MOAC), and Multidimensional Protein
      Identification Technology (MudPIT) including strong cation exchange (SCX)
      chromatography coupled with reversed phase (RP) HPLC. Proteins were identified by
      tandem mass spectrometry (MS/MS) using nanoelectrospray ionization hybrid
      quadrupole time-of-flight (QSTAR XL Hybrid LC/MS/MS System) and quadrupole ion
      trap (Thermo LCQ Deca). Results indicate that a SCX RP HPLC fractionation coupled
      with MS/MS provides the best high-throughput workflow for overall protein
      identification.

PMID- 18816082
TI  - Neuropeptidomics study profiles hypothalamic "nucleus", individual cells.

PMID- 18816083
TI  - Proteome analysis of multidrug resistance of human oral squamous carcinoma cells
      using CD147 silencing.
AB  - There is a correlation between the multidrug-resistance (MDR) of cancer cells and
      their enhanced invasive or metastatic potential. We studied the expression of
      CD147, a plasma membrane glycoprotein that plays a key role in tumor metastasis
      by stimulating the production of matrix metalloproteinases (MMPs), in sensitive
      human oral squamous KB and MDR derivative KB/V cells. Reverse transcription-PCR
      and flow cytometric analysis revealed that KB/V cells expressed CD147 at
      significantly higher levels than their parental KB cells. Using stable RNA
      interference, we succeeded in establishing a CD147 knock-down KB/V cell line
      (KB/VsiCD147). MTT colorimetric assay showed an increase in the chemosensitivity
      to vincristine (VCR), all transretinoic acid (ATRA), taxol, and 5-fluorouracil (5
      Fu) of KB/VsiCD147 cells. Proteome analysis of KB, KB/V, and KB/VsiCD147 cell
      lines identified 21 differently expressed proteins. The enhanced expression of
      representative active proteins, GRP75 and CyPA, was confirmed by Western blotting
      and RT-PCR. In addition, pretreatment of KB/V cells with a CyPA-binding
      immunosuppressive drug, cyclosporine A (CsA), enhanced their chemosensitivity to
      VCR and 5-Fu. We document an abundance of molecules that interact with CD147 in
      the MDR of human oral squamous carcinoma cells. Additional studies are needed to
      investigate these novel target proteins of CD147.

PMID- 18816084
TI  - Screening for EphB signaling effectors using SILAC with a linear ion trap
      orbitrap mass spectrometer.
AB  - Erythropoietin-producing hepatocellular carcinoma (Eph) receptors play important
      roles in development, neural plasticity, and cancer. We used an Orbitrap mass
      spectrometer and stable isotope labeling by amino acids in cell culture (SILAC)
      to identify and quantify 204 proteins with significantly changed abundance in
      antiphosphotyrosine immunoprecipitates after ephrinB1-Fc stimulation. More than
      half of all known effectors downstream of EphB receptors were identified in this
      study, as well as numerous novel candidates for EphB signaling.

PMID- 18816085
TI  - Neuropeptidomics of the supraoptic rat nucleus.
AB  - The mammalian supraoptic nucleus (SON) is a neuroendocrine center in the brain
      regulating a variety of physiological functions. Within the SON, peptidergic
      magnocellular neurons that project to the neurohypophysis (posterior pituitary)
      are involved in controlling osmotic balance, lactation, and parturition, partly
      through secretion of signaling peptides such as oxytocin and vasopressin into the
      blood. An improved understanding of SON activity and function requires
      identification and characterization of the peptides used by the SON. Here, small
      volume sample preparation approaches are optimized for neuropeptidomic studies of
      isolated SON samples ranging from entire nuclei down to single magnocellular
      neurons. Unlike most previous mammalian peptidome studies, tissues are not
      immediately heated or microwaved. SON samples are obtained from ex vivo brain
      slice preparations via tissue punch and the samples processed through sequential
      steps of peptide extraction. Analyses of the samples via liquid chromatography
      mass spectrometry and tandem mass spectrometry result in the identification of 85
      peptides, including 20 unique peptides from known prohormones. As the sample size
      is further reduced, the depth of peptide coverage decreases; however, even from
      individually isolated magnocellular neuroendocrine cells, vasopressin and several
      other peptides are detected.

PMID- 18816086
TI  - Insight into the phosphoryl transfer of the Escherichia coli glucose
      phosphotransferase system from QM/MM simulations.
AB  - Phosphoryl transfer is a key reaction in many aspects of metabolism, gene
      regulation, and signal transduction. One prominent example is the
      phosphoenolpyruvate:sugar phosphotransferase system (PTS), which represents an
      integral part of the bacterial sugar metabolism. The transfer between the enzymes
      IIA (Glc) and IIB (Glc) in the glucose-specific branch of the PTS is of
      particular interest due to the unusual combination of donor and acceptor residues
      involved in phosphoryl transfer: The phosphoryl group is initially attached to
      the Nepsilon2 atom of His 90 in IIA (Glc) and then transferred to the S gamma
      atom of Cys 35 in IIB (Glc). To gain insight into the details of the transfer
      mechanism, we have performed a QM/MM simulation which treats the entire active
      site quantum-mechanically. The transfer has a high dissociative character, and
      the Nepsilon2-P bond gets immediately destabilized after complex formation by
      numerous interactions formed between residues of IIB (Glc) and the phosphoryl
      group. The final formation of a tight S gamma-P bond is accompanied by a
      reorientation of the side chain of the phosphoryl donor. This reorientation
      results in the loss of interaction between the imidazole ring and the phosphate
      group thus hindering the reverse transfer. A comparison to the transfer in
      protein tyrosine phosphatases, which also use a cysteine as acceptor of the
      phosphoryl group, reveals significant similarities in the conformation of the
      active site, the energy profile of the reaction, and in the pattern of
      interactions that stabilize the phosphoryl group during the transfer.

PMID- 18816087
TI  - Systematic kinetics study of FoF1-ATPase: analytic results and comparison with
      experiments.
AB  - The systematic kinetics of the holoenzyme F oF 1-ATPase has been investigated by
      a tri-site filled, random binding order, and stochastic mechanochemical tight
      coupling model. The connection between the mechanical rotation speed and the
      chemical quantities such as the concentrations of substrates, the proton motive
      force, and the mechanical damping coefficient, has been analytically derived. The
      enzymatics based on ensemble experiments and single-molecule assays can be
      discussed systematically. Our model predictions agree well with both ensemble and
      single-molecule experimental results. Furthermore, this model can be used to
      study the dynamics of F oF 1-ATPase in a vesicle system.

PMID- 18816089
TI  - Heme electron transfer in peroxidases: the propionate e-pathway.
AB  - Computational modeling offers a new insight about the electron transfer pathway
      in heme peroxidases. Available crystal structures have revealed an intriguing
      arrangement of the heme propionate side chains in heme-heme and heme-substrate
      complexes. By means of mixed quantum mechanical/molecular mechanics calculations,
      we study the involvement of these propionate groups into the substrate oxidation
      in ascorbate peroxidase and into the heme to heme electron transfer in bacterial
      cytochrome c peroxidase. By selectively turning on/off different quantum regions,
      we obtain the electron transfer pathway which directly involves the porphyrin
      ring and the heme propionates. Furthermore, in ascorbate peroxidase the presence
      of the substrate appears to be crucial for the activation of the electron
      transfer channel. The results might represent a general motif for electron
      transfer from/to the heme group and change our view for the propionate side
      chains as simple electrostatic binding anchors. We name the new mechanism "the
      propionate e-pathway".

PMID- 18816090
TI  - Crystallization behaviors of n-octadecane in confined space: crossover of rotator
      phase from transient to metastable induced by surface freezing.
AB  - In this paper, the confined crystallization and phase transition behaviors of n
      octadecane in microcapsules with a diameter of about 3 microm were studied with
      the combination of differential scanning calorimetry (DSC), temperature dependent
      Fourier transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD). The
      main discovery is that the microencapsulated n-octadecane crystallizes into a
      stable triclinic phase via a mestastable rotator phase (R I), which emerges as a
      transient state for the bulk n-octadecane and is difficult to be detected by the
      commonly used characterization methods. As evident from the DSC measurement, a
      surface freezing monolayer, which is formed at the interface between the
      microcapsule inner wall and n-octadecane, induces the crossover of the R I from
      transient to metastable. We argue that the existence of the surface freezing
      monolayer decreases the nucleating potential barrier of the R I phase, and
      consequently the lower relative nucleation barrier in the confined geometry turns
      the transient R I phase into a metastable one.

PMID- 18816091
TI  - Detergent-associated solution conformations of helical and beta-barrel membrane
      proteins.
AB  - Membrane proteins present major challenges for structural biology. In particular,
      the production of suitable crystals for high-resolution structural determination
      continues to be a significant roadblock for developing an atomic-level
      understanding of these vital cellular systems. The use of detergents for
      extracting membrane proteins from the native membrane for either crystallization
      or reconstitution into model lipid membranes for further study is assumed to
      leave the protein with the proper fold with a belt of detergent encompassing the
      membrane-spanning segments of the structure. Small-angle X-ray scattering was
      used to probe the detergent-associated solution conformations of three membrane
      proteins, namely bacteriorhodopsin (BR), the Ste2p G-protein coupled receptor
      from Saccharomyces cerevisiae, and the Escherichia coli porin OmpF. The results
      demonstrate that, contrary to the traditional model of a detergent-associated
      membrane protein, the helical proteins BR and Ste2p are not in the expected,
      compact conformation and associated with detergent micelles, while the beta
      barrel OmpF is indeed embedded in a disk-like micelle in a properly folded state.
      The comparison provided by the BR and Ste2p, both members of the 7TM family of
      helical membrane proteins, further suggests that the interhelical interactions
      between the transmembrane helices of the two proteins differ, such that BR, like
      other rhodopsins, can properly refold to crystallize, while Ste2p continues to
      prove resistant to crystallization from an initially detergent-associated state.

PMID- 18816092
TI  - Fluorescence resonance energy transfer in polydiacetylene liposomes.
AB  - Conjugated polydiacetylene (PDA) possessing stimuli-responsive properties has
      been intensively investigated for developing efficient sensors. We report here
      fluorescence resonance energy transfer (FRET) in liposomes synthesized using
      different molar ratios of dansyl-tagged diacetylene and diacetylene-carboxylic
      acid monomers. Photopolymerization of diacetylene resulted in cross-linked PDA
      liposomes. We used steady-state electronic absorption, emission, and fluorescence
      anisotropy (FA) analysis to characterize the thermal-induced FRET between dansyl
      fluorophores (donor) and PDA (acceptor). We found that the monomer ratio of
      acceptor to donor ( R ad) and length of linkers (functional part that connects
      dansyl fluorophores to the diacetylene group in the monomer) strongly affected
      FRET. For R ad = 10 000, the acceptor emission intensity was amplified by more
      than 18 times when the liposome solution was heated from 298 to 338 K. A decrease
      in R ad resulted in diminished acceptor emission amplification. This was
      primarily attributed to lower FRET efficiency between donors and acceptors and a
      higher background signal. We also found that the FRET amplification of PDA
      emissions after heating the solution was much higher when dansyl was linked to
      diacetylene through longer and flexible linkers than through shorter linkers. We
      attributed this to insertion of dansyl in the bilayer of the liposomes, which led
      to an increased dansyl quantum yield and a higher interaction of multiple
      acceptors with limited available donors. This was not the case for shorter and
      more rigid linkers where PDA amplification was much smaller. The present studies
      aim at enhancing our understanding of FRET between fluorophores and PDA-based
      conjugated liposomes. Furthermore, receptor tagged onto PDA liposomes can
      interact with ligands present on proteins, enzymes, and cells, which will produce
      emission sensing signal. Therefore, using the present approach, there exist
      opportunities for designing FRET-based highly sensitive and selective chemical
      and biochemical sensors.

PMID- 18816094
TI  - A vibrational probe for local nucleic acid environments: 5-cyano-2'-deoxyuridine.
AB  - Nitriles have been shown to be effective vibrational probes of local environments
      in proteins but have yet to be fully utilized for the study of nucleic acids. The
      potential utility of 5-cyano-2'-deoxyuridine ( 1) as a probe of local nucleic
      acid environment was investigated by measuring the dependence of the IR nitrile
      stretching frequency (nu CN), line shape, and absorbance on solvent and
      temperature. The nu CN was found to be sensitive to solvent with an observed blue
      shift of 9.2 cm (-1) in going from THF to water. The dependence of the nitrile IR
      absorbance band was further investigated in water-THF mixtures. Global line shape
      analysis, difference FTIR spectroscopy, and singular value decomposition (SVD)
      were used to show the presence of three distinct local environments around the
      nitrile group of 1 in these mixtures. A modest blue shift in nu CN was observed
      upon a hydrogen-bond-mediated heterodimer formation between 2 (a silyl ether
      analogue of 1) and 2,6-diheptanamido-pyridine ( 3a) in chloroform. The intrinsic
      temperature dependence of the nu CN was found to be minimal and linear over the
      temperature range studied. The experimental studies were complemented by density
      functional theory (DFT) calculations on the dependence of the nitrile stretching
      frequency on solute-solvent interactions and upon heterodimer formation with
      model systems.

PMID- 18816095
TI  - Generic schemes for single-molecule kinetics. 1: Self-consistent pathway
      solutions for renewal processes.
AB  - In this paper, we discuss a strategy for reducing a complex single molecule
      kinetic process to a set of generic structures (motifs) that are building blocks
      for a general kinetic scheme. In general, these motifs have complex kinetics
      (i.e., waiting time distribution functions) which are composed of fundamental
      kinetic steps. (1) First, we treat four different experimental single molecule
      measurements within both the usual kinetic framework (i.e., using the rate
      matrix) and the waiting time distribution function framework. The two frameworks
      are then shown to be equivalent and can be formulated on the basis of the first
      passage time distribution function of monitored single molecule events. (2)
      Second, to calculate this basic quantity, we decompose a complex kinetic scheme
      with the help of two kinetic motifs, sequential and branching, and derive self
      consistent equations by convoluting waiting time distributions and first passage
      time distribution(s) along the reaction pathway(s). (3) As examples, two
      experimental systems, a chain reaction model with a special case of enzymatic
      reactions and a general kinetic model for fluorescence emission, are analyzed on
      the basis of a generic scheme composed of a monitored link, controlled link, and
      unknown link, each representing a possible subscheme associated with a complex
      waiting time distribution function. As a result, single molecule measurements of
      the generic scheme retain the same functional form when a kinetic link is altered
      within a subscheme, and different measurements can be classified and analyzed
      within the same framework. (4) Finally, to explore the physical reasons for
      nonexponential waiting time distribution, we use the example of blinking
      phenomena to discuss several scenarios of dynamic and static disorder and their
      implications for observed memory effects. The self-consistent pathway formalism
      is presented in this paper for renewal processes and will be generalized to
      nonrenewal processes with memory effects in a future publication.

PMID- 18816096
TI  - Investigating the effect of increasing charge density on the hemolytic activity
      of synthetic antimicrobial polymers.
AB  - The current study is aimed at investigating the effect of fine-tuning the
      cationic character of synthetic mimics of antimicrobial peptides (SMAMPs) on the
      hemolytic and antibacterial activities. A series of novel norbornene monomers
      that carry one, two, or three Boc-protected amine functionalities was prepared.
      Ring-opening metathesis polymerization (ROMP) of the monomers, followed by
      deprotection of the amine groups resulted in cationic antimicrobial
      polynorbornenes that carry one, two, and three charges per monomer repeat unit.
      Increasing the number of amine groups on the most hydrophobic polymer reduced its
      hemolytic activity significantly. To understand the membrane activity of these
      polymers, we conducted dye leakage experiments on lipid vesicles that mimic
      bacteria and red blood cell membranes, and these results showed a strong
      correlation with the hemolysis data.

PMID- 18816097
TI  - End-functionalized phosphorylcholine methacrylates and their use in protein
      conjugation.
AB  - Polymer-protein conjugation was performed using N-hydroxysuccinimide and aldehyde
      terminated zwitterionic polymers, and the resulting polymer-protein conjugates
      were characterized by gel electrophoresis and fast protein liquid chromatography.
      Methacryloyloxyethyl phosphorylcholine (MPC) polymers were prepared by atom
      transfer radical polymerization in which the requisite functional end-groups for
      protein conjugation were embedded within the polymerization initiators. These
      phosphorylcholine polymers were conjugated to lysozyme as a model protein, as
      well as two therapeutic proteins, granulocyte colony stimulating factor (G-CSF)
      and erythropoietin (EPO). These MPC polymer-protein conjugates represent
      alternatives to PEGylated proteins, with the potential to provide improved
      efficacy in a therapeutic treatment relative to the protein itself.

PMID- 18816098
TI  - Immobilization of growth factors on collagen scaffolds mediated by polyanionic
      collagen mimetic peptides and its effect on endothelial cell morphogenesis.
AB  - Angiogenesis, a morphogenic event endothelial cells (ECs) undergo in response to
      3-D environmental triggers, is critical to the survival and ultimate functional
      capacity of engineered tissue constructs. Here we present a new collagen mimetic
      peptide (CMP) architecture consisting of multiple anionic charges at the
      peptide's N-terminus designed to attract growth factors by charge-charge
      interactions and bind to collagen by CMP-collagen interaction. The anionic CMPs
      exhibited specific binding affinity to type I collagen substrates while
      attracting vascular endothelial growth factors (VEGFs), which led to enhanced
      morphological features of ECs, indicative of tubulogenesis. The results show that
      these new CMPs could be used to direct proliferation and differentiation of cells
      in collagen scaffolds by localization and sustained delivery of growth factors
      and other morphogens.

PMID- 18816099
TI  - Carboxymethyl chitosan as a matrix material for platinum, gold, and silver
      nanoparticles.
AB  - Carboxymethyl chitosan (CMC) was evaluated for its use in the synthesis and
      stabilization of catalytic nanoparticles for the first time. Many studies have
      reported on the ability of chitosan to bind with metal ions and support metal
      nanoparticles. CMC has a higher reported chelation capacity than chitosan, which
      has potential implications for improved catalyst formation and immobilization.
      Platinum, gold, and silver nanoparticles were synthesized in both chitosan and
      CMC. Particle size, morphology, and aggregation were examined using transmission
      electron microscopy (TEM). Complexation of nanoparticles was studied through
      Fourier transform infrared spectroscopy (FTIR). Similar nanoparticle size
      distributions were observed in the two polymers; however, CMC was observed to
      have higher rates of aggregation. This indicates that the carboxymethyl groups
      did not change nanoparticle formation; however, poor cross-linking and a limited
      anchoring ability of CMC led to the inability to immobilize the catalyst
      materials effectively.

PMID- 18816100
TI  - Novel genipin-cross-linked chitosan/silk fibroin sponges for cartilage
      engineering strategies.
AB  - The positive interaction of materials with tissues is an important step in
      regenerative medicine strategies. Hydrogels that are obtained from
      polysaccharides and proteins are expected to mimic the natural cartilage
      environment and thus provide an optimum milleu for tissue growth and
      regeneration. In this work, novel hydrogels composed of blends of chitosan and
      Bombyx mori silk fibroin were cross-linked with genipin (G) and were freeze dried
      to obtain chitosan/silk (CSG) sponges. CSG sponges possess stable and ordered
      structures because of protein conformational changes from alpha-helix/random-coil
      to beta-sheet structure, distinct surface morphologies, and pH/swelling
      dependence at pH 3, 7.4, and 9. We investigated the cytotoxicity of CSG sponge
      extracts by using L929 fibroblast-like cells. Furthermore, we cultured ATDC5
      cells onto the sponges to evaluate the CSG sponges' potential in cartilage repair
      strategies. These novel sponges promoted adhesion, proliferation, and matrix
      production of chondrocyte-like cells. Sponges' intrinsic properties and
      biological results suggest that CSG sponges may be potential candidates for
      cartilage tissue engineering (TE) strategies.

PMID- 18816101
TI  - A three-step route to a tricyclic steroid precursor.
AB  - 2-Alkyl cyclohexenones are useful intermediates for organic synthesis. The Wittig
      reaction of a series of aldehydes with (cyclopropylmethyl)triphenylphosphonium
      bromide delivered the corresponding alkenyl cyclopropanes. UV irradiation in the
      presence of Fe(CO)5 converted the alkenyl cyclopropanes to the 2-substituted
      cyclohexenones. This approach enabled a three-step synthesis of the tricyclic
      core of estrone methyl ether.

PMID- 18816102
TI  - In-adamantane, a small inside-out molecule.
AB  - The hydrocarbon in-adamantane (1), a high-energy adamantane isomer in which one
      methine hydrogen atom is inside the cage, is predicted by ab initio calculations
      to be isolable at dry ice temperature. It has 440 kJ/mol of hydrogenic strain but
      appears to be stable against dimerization, moisture, and air. The inverted CH
      bond is compressed, and the IR and NMR spectra are unusual. The symmetrical
      pentadecafluoro derivative (2) has an estimated half-life of 100 years at room
      temperature.

PMID- 18816103
TI  - A route to 1,4-disubstituted aromatics and its application to the synthesis of
      the antibiotic culpin.
AB  - A method is described for converting tert-butyl benzoates or tert-butyl 1
      naphthoates into derivatives having an alkyl or substituted alkyl group in a 1,4
      relationship to an alkyl, aryl, alkenyl, or alkynyl group. Key steps in the
      sequence are (i) addition of an organometallic species to a cross-conjugated
      cyclohexadienone obtained by Birch alkylation of a tert-butyl benzoate or a tert
      butyl 1-naphthoate, followed by allylic oxidation, and (ii) treatment with BiCl3
      x H2O, which results in removal of the tert-butyl group and spontaneous
      decarboxylative aromatization. The method was applied to the synthesis of the
      antimicrobial fungal metabolite culpin.

PMID- 18816104
TI  - Regiochemical effects of sulfur oxidation on the electronic and solid-state
      properties of planarized oligothiophenes containing thieno[3,2-b]thiophene units.
AB  - The effect of position and degree of sulfur oxidation on the fundamental
      properties of a series of planarized thieno[3,2-b]thiophene S,S-dioxides
      derivatives was studied. The optical data reveal a red shift in the longest
      wavelength of absorption relative to the nonoxidized analogues that is indicative
      of a reduced HOMO-LUMO gap. The position of oxidation rather than the extent of
      oxidation is the most critical factor in controlling electronic properties.
      Single-crystal analysis reveals that some of the oligothiophene S,S-dioxides
      studied present pi-pi interactions which are completely absent in the nonoxidized
      analogue.

PMID- 18816105
TI  - Photoinduced three-component reactions of tetracyanobenzene with alkenes in the
      presence of 1,3-dicarbonyl compounds as nucleophiles.
AB  - Photoinduced three-component reactions between tetracyanobenzene (TCNB), an
      aromatic olefin, and a beta-dicarbonyl compound afford products composed of the
      three components via formal elimination of hydrogen cyanide, leading to the
      vicinal dialkylation of the olefin and the alpha-alkylation of the beta
      dicarbonyl compounds. It is shown that these reactions are initiated by
      photoinduced electron transfer (PET) from the olefin to the singlet excited TCNB
      and proceed by a nucleophile-olefin combination, aromatic substitution (NOCAS)
      reaction sequence with the enolized beta-dicarbonyl compound as a nucleophile.
      Therefore, aromatic olefins are suitable substrates in photo-NOCAS reactions when
      TCNB is used as the electron acceptor. In addition, these results show that the
      enol of beta-dicarbonyl compound serves as a carbon nucleophile to trap the
      alkene cation radical in PET reactions to lead to C-C bond formation.

PMID- 18816107
TI  - Charge-dependent cavity radii for an accurate dielectric continuum model of
      solvation with emphasis on ions: aqueous solutes with oxo, hydroxo, amino,
      methyl, chloro, bromo, and fluoro functionalities.
AB  - Dielectric continuum solvation models are widely used because they are a
      computationally efficacious way to simulate equilibrium properties of solutes.
      With advances that allow for molecular-shaped cavities, they have reached a high
      level of accuracy, in particular for neutral solutes. However, benchmark tests
      show that existing schemes for defining cavities are unable to consistently
      predict accurately the effects of solvation on ions, especially anions. This work
      involves the further development of a protocol put forth earlier for defining the
      cavities of aqueous solutes, with resulting advances that are most striking for
      anions. Molecular cavities are defined as interlocked spheres around atoms or
      groups of atoms in the solute, but the sphere radii are determined by simple
      empirically based expressions involving the effective atomic charges of the
      solute atoms (derived from molecular electrostatic potential) and base radii.
      Both of these terms are optimized for the different types of atoms or functional
      groups in a training set of neutral and charged solutes. Parameters in these
      expressions for radii were fitted by minimizing residuals between calculated and
      measured standard free energies of solvation (DeltaG(s)*), weighted by the
      uncertainty in the measured value. The calculations were performed using density
      functional theory with the B3LYP functional and the 6-311+G** basis set and the
      COnductor-like Screening MOdel (COSMO). The optimized radii definitions reproduce
      DeltaG(s)* of neutral solutes and singly charged ions in the training set to
      within experimental uncertainty and, more importantly, accurately predict
      DeltaG(s)* of compounds outside the training set, in particular anions (J. Phys.
      Chem. A 2003, 107, 5778). Inherent to this approach, the cavity definitions
      reflect the strength of specific solute-water interactions. We surmise that this
      feature underlies the success of the model, referred to as the CD-COSMO model for
      Charge-Dependent (also Camaioni-Dupuis) COSMO model. These findings offer
      encouragement that we can keep extending this scheme to other functional groups
      and obtain better accuracy in using continuum solvation models to predict
      equilibrium properties of aqueous ionic solutes. The approach is illustrated for
      a number of test cases, including the determination of acidities of an amine
      base, a study of the tautomerization equilibrium of a zwitterionic molecule
      (glycine), and calculating solvation energies of transition states toward a full
      characterization of reaction pathways in aqueous phase, here in S(N)2 exchange
      reactions. The calculated reaction barriers in aqueous solution are in excellent
      agreement with experimental values.

PMID- 18816108
TI  - Synthetic and immunological studies of 5'-N-phenylacetyl sTn to develop
      carbohydrate-based cancer vaccines and to explore the impacts of linkage between
      carbohydrate antigens and carrier proteins.
AB  - 5'- N-Phenylacetyl sTn (sTnNPhAc), an unnatural derivative of sTn antigen
      expressed by many tumors, and its alpha-linked protein conjugates were prepared
      and investigated to explore glycoconjugate cancer vaccines. sTnNPhAcalpha-KLH
      elicited a robust T cell dependent immunity. The antiserum derived from
      sTnNPhAcalpha- or sTnNPhAcbeta-KLH-inoculated mice was similarly reactive to
      sTnNPhAcalpha and sTnNPhAcbeta but showed very little reactivity to sTn,
      NeuNPhAcalpha(2,3)GalNAc--a regioisomer of sTnNPhAc, isolated phenylacetyl group,
      and the linker employed to conjugate sTnNPhAc and carrier protein. It was
      concluded that the sTnNPhAc-elicited immunity was specific for the whole antigen
      rather than the phenylacetyl group or other partial structures of sTnNPhAc and
      that the reducing end configuration or linkage of sTnNPhAc did not affect its
      immunological identity. It was also concluded that a new linker designed to
      conjugate carbohydrates and proteins did not provoke any immune reaction and that
      the linker, as well as the associated new and convenient coupling strategy, can
      be safely used for the development of glycoconjugate vaccines.

PMID- 18816109
TI  - Ni(II), Cu(II), and Zn(II) diethyldithiocarbamate complexes show various
      activities against the proteasome in breast cancer cells.
AB  - A series of three complexes with diethyldithiocarbamate ligand and three
      different metals (Ni, Cu, Zn) was prepared, confirmed by X-ray crystallography,
      and tested in human breast cancer MDA-MB-231 cells. Zinc and copper complexes,
      but not nickel complex, were found to be more active against cellular 26S
      proteasome than against purified 20S proteasome core particle. One of the
      possible explanations is inhibition of JAMM domain in the 19S proteasome lid.

PMID- 18816110
TI  - Soluble 3',6-substituted indirubins with enhanced selectivity toward glycogen
      synthase kinase -3 alter circadian period.
AB  - Glycogen synthase kinase -3 (GSK-3) is a key enzyme involved in numerous
      physiological events and in major diseases, such as Alzheimer's disease,
      diabetes, and cardiac hypertrophy. Indirubins are bis-indoles that can be
      generated from various natural sources or chemically synthesized. While rather
      potent and selective as GSK-3 inhibitors, most indirubins exhibit low water
      solubility. To address the issue of solubility, we have designed novel analogues
      of 6-bromo-indirubin-3'-oxime with increased hydrophilicity based on the GSK
      3/indirubins cocrystal structures. The new derivatives with an extended amino
      side chain attached at position 3' showed potent GSK-3 inhibitory activity,
      enhanced selectivity, and dramatically increased water solubility. Furthermore,
      some of them displayed little or no cytotoxicity. The new indirubins inhibit GSK
      3 in a cellular reporter model. They alter the circadian period measured in
      rhythmically expressing cell cultures, suggesting that they might constitute
      tools to investigate circadian rhythm regulation.

PMID- 18816111
TI  - Gedunin, a novel hsp90 inhibitor: semisynthesis of derivatives and preliminary
      structure-activity relationships.
AB  - Gedunin (1), a tetranortriterpenoid isolated from the Indian neem tree (
      Azadirachta indica), was recently shown to manifest anticancer activity via
      inhibition of the 90 kDa heat shock protein (Hsp90) folding machinery and to
      induce the degradation of Hsp90-dependent client proteins similar to other Hsp90
      inhibitors. The mechanism of action by which gedunin induces client protein
      degradation remains undetermined, however, prior studies have demonstrated that
      it does not bind competitively versus ATP. In an effort to further probe the
      mechanism of action, 19 semisynthetic derivatives of gedunin were prepared and
      their antiproliferative activity against MCF-7 and SkBr3 breast cancer cells
      determined. Although no compound was found to exhibit antiproliferative activity
      more effective than the natural product, functionalities critical for
      antiproliferative activity have been identified.

PMID- 18816113
TI  - Donors and acceptors based on triangular dehydrobenzo[12]annulenes: formation of
      a triple-layered rosette structure by a charge-transfer complex.
AB  - We present here the results of studies of the synthesis and properties of donors
      and acceptors based on triangular dehydrobenzo[12]annulene ([12]DBA) system as a
      pi core. These studies were aimed at controlling the supramolecular crystal
      structure. Toward this end, the tricyano[12]DBA 2 and dodecafluoro[12]DBA ( 3)
      were synthesized as acceptors (A) and the tris(dialkylamino)[12]DBAs 4a-d as
      donors (D), and their electronic properties were determined by electronic
      absorption spectroscopy and electrochemical measurements. The main focus, though,
      was the formation of supramolecular structures in crystals. These compounds form
      distinct packing patterns as a result of the different intermolecular
      interactions. Tricyano[12]DBA 2 forms a two-dimensional (2D) sheet structure via
      hydrogen-bonding interactions, whereas a tilted-stack structure was found for 3
      because of the lack of significant intermolecular interactions.
      Tris(dibutylamino)[12]DBA 4b exhibits a ladder-type 2D structure, probably
      because of van der Waals interactions between the butyl groups. The most
      significant finding is that charge-transfer interactions between donor 4a and
      acceptor 3 combined with their triangular molecular shapes and lateral CH...F
      hydrogen bonding result in the formation of a 2D rosette structure consisting of
      two different trimeric (DAD- and ADA-type) sandwich structures with 1:2 and 2:1
      A/D ratios, respectively.

PMID- 18816114
TI  - Design of liquid crystals with "de Vries-like" properties: organosiloxane mesogen
      with a 5-phenylpyrimidine core.
AB  - According to a new design strategy for "de Vries-like" liquid crystal materials,
      we report the synthesis and characterization of an organosiloxane mesogen with a
      5-phenylpyrimidine core that forms SmA and SmC liquid crystal phases. This new
      material is characterized by a maximum layer contraction of 1.2% upon SmA-SmC
      phase transition and is comparable to the best "de Vries-like" materials reported
      heretofore.

PMID- 18816115
TI  - Organocatalytic asymmetric transferhydrogenation of beta-nitroacrylates:
      accessing beta2-amino acids.
AB  - We describe a highly efficient and enantioselective Hantzsch ester mediated
      conjugate reduction of beta-nitroacrylates that is catalyzed by a Jacobsen
      thiourea catalyst as a key step in a new route to optically active beta2-amino
      acids.

PMID- 18816116
TI  - One-dimensional optoelectronic nanostructures derived from the aqueous self
      assembly of pi-conjugated oligopeptides.
AB  - The aqueous self-assembly of oligopeptide-flanked pi-conjugated molecules into
      discrete one-dimensional nanostructures is described. Unique to these molecules
      is the fact that the pi-conjugated unit has been directly embedded within the
      peptide backbone by way of a synthetic amino acid with pi-functionality that is
      compatible with standard Fmoc-based peptide synthesis. The peptide-based
      molecular design enforces intimate pi-pi communication within the aggregate after
      charge-screening and self-assembly, making these nanostructures attractive for
      optical or electronic applications in biological environments. The synthesis and
      assembly are reported along with spectroscopic and morphological characterization
      of the new nanomaterials.

PMID- 18816117
TI  - Extraordinary circularly polarized luminescence activity exhibited by cesium
      tetrakis(3-heptafluoro-butylryl-(+)-camphorato) Eu(III) complexes in EtOH and
      CHCl3 solutions.
AB  - The largest CPL activity ever measured was observed for cesium tetrakis(3
      heptafluoro-butylryl-(+)-camphorato) Eu(III) complexes in EtOH and CHCl3
      solutions substantiating the stereospecific formation of chiral Delta-SAPR-(C4)
      configuration with the aid of Cs+...FC (fluorocarbon) interactions more clearly
      than the exciton CD spectra.

PMID- 18816118
TI  - Catalytic use of indium(0) for carbon-carbon bond transformations in water:
      general catalytic allylations of ketones with allylboronates.
AB  - We have discovered the unprecedented catalytic use of In(0) for catalytic C-C
      bond transformations. Remarkably, these general catalytic allylations of ketones
      proceeded smoothly in water as a sole solvent under mild conditions, and water
      proved to be essential for these reactions. Both the displayed substrate scope
      and the functional group tolerance were excellent. Importantly, the In metal
      catalyst could be easily recovered and reused without loss of catalytic activity.
      Moreover, when an alpha-substituted allylboronate was used, an unusual
      constitutional selectivity was observed providing exclusively the formal alpha
      adduct. Additionally, the resulting tertiary homoallylic alcohols were obtained
      with exceptionally high diastereoselectivities. The applicability of this concept
      to asymmetric catalysis in water by using In(0) combined with a chiral
      bis(oxazoline) ligand was demonstrated as well.

PMID- 18816119
TI  - Synthesis of the tricyclic core of alkaloid securinol B using a cascade of
      Vilsmeier-Haack and Mannich cyclizations.
AB  - Iminium ions generated upon amide activation were trapped sequentially with
      tethered nucleophiles. This cascade of cyclizations constitutes a new synthetic
      strategy that was applied to the construction of the tricyclic core of alkaloid
      securinol B.

PMID- 18816120
TI  - Isolation, structure determination, and synthesis of galaxamide, a rare cytotoxic
      cyclic pentapeptide from a marine algae Galaxaura filamentosa.
AB  - Galaxamide (1), a rare cyclic pentapeptide, was isolated from the marine algae
      Galaxaura filamentosa. A preliminary bioassay of Galaxamide showed remarkable in
      vitro antiproliferative activities against GRC-1 and HepG2 cell lines. The first
      total synthesis of the cyclic peptide was achieved for further biological
      evaluation.

PMID- 18816121
TI  - Manipulating replication processes within a dynamic covalent framework.
AB  - The reaction of an amine bearing an amidopyridine recognition site and an
      aldehyde bearing a carboxylic acid recognition site affords an imine that is
      capable of directing its own formation through a dynamic covalent replication
      cycle. Additionally, the amine, formed by reduction of the replicating imine, is
      a more efficient catalyst for the formation of the replicating imine than the
      imine is a catalyst for its own formation.

PMID- 18816122
TI  - (1-Naphthyl)(trifluoromethyl) O-carboxy anhydride as a chiral derivatizing agent:
      eclipsed conformation enforced by hydrogen bonding.
AB  - The preparation of the (1-naphthyl)(trifluoromethyl) O-carboxy-anhydride 1 and
      its use as a chiral derivatizing agent with several alpha-chiral primary amines
      are reported. The very large Delta delta(RS) values observed in (1)H NMR have
      been correlated with a marked preference of the corresponding alpha-hydroxy
      amides for the eclipsed conformation. In comparison, the related O-methylated
      amides are shown to adopt staggered conformations, which substantiates the
      critical role of intramolecular hydrogen bonding in maximizing the anisotropic
      effect.

PMID- 18816123
TI  - A chemoenzymatic total synthesis of the structure assigned to the alkaloid (+)
      montabuphine.
AB  - An enantioselective synthesis of the structure, 3, assigned to the alkaloid (+)
      montabuphine has been achieved using the readily available metabolite 4 as
      starting material. A comparison of the physical and spectral data recorded on
      compound 3 with those reported for (+)-montabuphine suggests that they are
      different compounds.

PMID- 18816124
TI  - Enantiopure 2-substituted glyceraldehyde derivatives by aza-Claisen rearrangement
      or C-alkylation of enamines.
AB  - 2-Alkyl derivatives of butane-2,3-diacetal (BDA) protected glyceraldehyde were
      stereoselectively prepared by aza-Claisen rearrangement of N-allyl-enammonium
      ions or C-alkylation of enamines. This allows rapid and convenient access to
      densely functionalized chiral building blocks.

PMID- 18816125
TI  - Synthesis of anthracene and azaanthracene fluorophores via [2+2+2]
      cyclotrimerization reactions.
AB  - A highly convergent [2+2+2] cyclotrimerization approach to anthracenes and 2
      azaanthracenes has been developed. It allows for the facile introduction of the
      anthracene moiety on alkyne and nitrile bearing molecules and the rapid
      construction of compound arrays. This is showcased in the assembly of a
      collection of fluorophores and their photochemical evaluation.

PMID- 18816126
TI  - 1-substituted 5-aminotetrazoles: syntheses from CNN3 with primary amines.
AB  - 1-Substituted 5-aminotetrazoles were prepared in situ by an excellent reaction of
      cyanogen azide and primary amines to generate an imidoyl azide as an intermediate
      in acetonitrile/water. After cyclization, the intermediate gave 1-substituted
      aminotetrazole in good yield. This protocol also was utilized in the syntheses of
      bis- and tris(1-substituted 5-aminotetrazole) derivatives.

PMID- 18816127
TI  - Potassium t-butoxide alone can promote the biaryl coupling of electron-deficient
      nitrogen heterocycles and haloarenes.
AB  - The biaryl coupling of electron-deficient nitrogen heterocycles and haloarenes
      can be promoted by potassium t-butoxide alone, without the addition of any
      exogenous transition metal species. Electron-deficient nitrogen heterocycles such
      as pyridine, pyridazine, pyrimidine, pyrazine, and quinoxaline are arylated with
      haloarenes. Control experiments support a radical-based mechanism. Taking these
      findings into account, radical processes may be partially involved in the
      reported transition-metal-catalyzed arylation reactions employing t-butoxide
      bases and haloarenes under elevated temperatures or under microwave irradiation.

PMID- 18816128
TI  - The first synthesis of a novel 5:7:5-fused diimidazodiazepine ring system and
      some of its chemical properties.
AB  - The first synthesis of a novel 5:7:5-fused heterocyclic ring system, a
      diimidazodiazepine, is reported. The propensity of the ring system to undergo
      facile, acid-catalyzed nucleophilic addition reactions by neutral carbon and
      nitrogen nucleophiles has been explored. The ring system has potential future
      applications in mechanistic studies of formation and repair of DNA interstrand
      cross-links.

PMID- 18816129
TI  - Total synthesis of neolaulimalide and isolaulimalide.
AB  - The first total syntheses of the potential antitumoral leads neolaulimalide (2)
      and isolaulimalide (3) have been achieved. Key steps in our convergent, fully
      stereocontrolled route are a Yamaguchi macrolactonization, a Julia-Lythgoe
      Kocienski olefination, a Kulinkovich reaction, and a cyclopropyl-allyl
      rearrangement to install the exo-methylene group. Overall, we synthesized 2 in 21
      linear steps (3% yield) and 3 in 24 steps (2% yield).

PMID- 18816130
TI  - Trans-stereoselectivity in the reaction between homophthalic anhydride and
      imines.
AB  - The reaction between homophthalic anhydride and imines in the presence of TiCl4
      and diisopropyl ethyl amine is trans-selective. Under these conditions, the
      reaction using homochiral imines can be highly diastereoselective, thus allowing
      the synthesis of enantiopure 1,2,3,4-tetrahydro-1-oxoquinoline-4-carboxylic
      acids.

PMID- 18816131
TI  - B,O-chelated azadipyrromethenes as near-IR probes.
AB  - Complementary synthetic routes to a new class of near-IR fluorophores are
      described. These allow facile access (four synthetic steps) to the core
      fluorophore and substituted derivatives with emissions between 740 and 780 nm in
      good quantum yields.

PMID- 18816132
TI  - Cationic and fluorescent "Janus" dendrimers.
AB  - Two synthetic routes to "Janus"-type dendrimers possessing ammonium groups on one
      side and fluorescent dansyl derivatives on the other side are described. These
      surface-block dendrimers are obtained by the coupling of two different dendrons,
      built from the hexafunctional cyclotriphosphazene core. Their characterization
      and their photophysical behavior are reported. The largest compound possesses 10
      ammonium groups and 5 dansyl groups; it is potentially useful as a fluorescent
      label in materials science and biology.

PMID- 18816133
TI  - Rhenium(VII) catalysis of Prins cyclization reactions.
AB  - The rhenium(VII) complex O3ReOSiPh3 is a particularly effective catalyst for
      Prins cyclizations using aromatic and alpha,beta-unsaturated aldehydes. The
      reaction conditions are mild, and the highly substituted 4-hydroxytetrahydropyran
      products are formed stereoselectively. Rhenium(VII) complexes appear to
      spontaneously form esters with alcohols and to directly activate electron-rich
      alcohols for solvolysis. Re2O7 and perrhenic acid are equally effective in
      catalyzing these cyclizations.

PMID- 18816134
TI  - Total synthesis of (+/-)-calcaridine A and (+/-)-epi-calcaridine A.
AB  - The first total synthesis of the Leucetta alkaloid calcaridine A is described
      based on a biosynthetic postulate. Application of an oxidative rearrangement of a
      4,5-disubstituted imidazole leads to the formation of both calcaridine A and epi
      calcaridine A. An X-ray crystal structure determination on the latter has allowed
      the assignment of the relative configuration of the epimeric natural product and
      calcaridine A by extrapolation.

PMID- 18816135
TI  - Copper-catalyzed one-pot multicomponent coupling reaction of phenols, amides, and
      4-bromphenyl iodide.
AB  - An efficient copper-catalyzed multicomponent reaction of phenols, amides, and 4
      bromphenyl iodide was developed that uses commercially available N,N
      dimethylglycine as the ligand. This multicomponent reaction proceeds in moderate
      to good yields for a range of phenols and amides. The simple experimental
      procedure and high levels of functional group compatibility make this method
      attractive for applications on pesticides.

PMID- 18816136
TI  - High temperature metalation of functionalized aromatics and heteroaromatics using
      (tmp)2Zn x 2 MgCl2 x 2 LiCl and microwave irradiation.
AB  - A wide range of polyfunctional aryl and heteroaryl zinc reagents were efficiently
      prepared in THF via direct zincation using (tmp)2Zn x 2 MgCl2 x 2 LiCl and
      microwave irradiation. Ester and cyano functions as well as ketones are
      compatible with the high temperatures of the zincation. The resulting bis-organo
      zinc species undergo a number of subsequent reactions leading to highly
      functionalized aromatics and heteroaromatics in good to excellent yields.

PMID- 18816137
TI  - Diastereoselective synthesis of cyclopentapyridazinones via radical cyclization:
      synthetic studies toward halichlorine.
AB  - The pyridazinone ring system serves as an excellent scaffold for the
      diastereoselective preparation of novel cis-fused cyclopentapyridazinones
      utilizing the directed 5-exo radical cyclization approach. This overall approach
      was successfully employed in the preparation of a functionalized aza-spirocycle.

PMID- 18816138
TI  - Synthesis of D- and L-carbocyclic nucleosides via rhodium-catalyzed asymmetric
      hydroacylation as the key step.
AB  - D- and L-carbocyclic nucleosides were obtained by a new procedure involving an
      enantioselective rhodium/duphos-catalyzed hydroacylation reaction as the key
      step. The 3-hydroxymethyl-cyclopentanol intermediate was obtained by
      stereoselective reduction of ketone and by dynamic kinetic resolution (DKR).

PMID- 18816139
TI  - Evidence for the mechanism of action of the antifungal phytolaccoside B isolated
      from Phytolacca tetramera Hauman.
AB  - Phytolaccoside B (1), an antifungal monodesmoside triterpenoid glycoside isolated
      from berries of Phytolacca tetramera Hauman (Phytolaccaceae), alters the
      morphology of yeasts and molds. The malformations were similar to those produced
      by enfumafungin, a known inhibitor of (1-->3)-beta-D-glucan synthase, an enzyme
      that catalyzes the synthesis of (1-->3)-beta-D-glucan, one of the major polymers
      of the fungal cell wall. However, enzymatic assays revealed that 1 did not
      inhibit (1-->3)-beta-D-glucan synthase, but it did produce a notable enhancement
      of the chitin synthase 1 activity and, concomitantly, a rise in chitin, another
      important polymer of the fungal cell walls. This finding was corroborated by
      fluorescence microscopy and also by quantification of the chitin. In addition, a
      2-fold increase in the thickness of the fungal cell wall was observed with
      transmission electronic microscopy. On the other hand, 1 neither bound to
      ergosterol nor caused hemolysis of red blood cells, although some fungal membrane
      damage was observed at the MIC of 1.

PMID- 18816140
TI  - Formal cycloaddition of disubstituted ketenes with 2-oxoaldehydes catalyzed by
      chiral N-heterocyclic carbenes.
AB  - Chiral N-hetereocyclic carbenes were found to be efficient catalysts for the
      formal [2 + 2] cycloaddition reactions of alkyl(aryl)ketenes with 2-oxoaldehydes
      to afford beta-lactones with alpha-quaternary-beta-tertiary stereocenters in high
      yields with good diastereoselectivities and excellent enantioselectivities (up to
      99% ee). Both alkyl(aryl)ketenes and diarylketene worked well in this reaction.

PMID- 18816141
TI  - Enantiopure quaternary alpha-trifluoromethyl-alpha-alkoxyaldehydes from L
      tartaric acid derived ketoamides.
AB  - The diastereoselective nucleophilic trifluoromethylation of a range of ketoamides
      derived from L-tartaric acid has been studied. TMSCF3 in the presence of a
      catalytic amount of K2CO3 in DMF has been identified as the conditions leading to
      the highest diastereoselectivities. A sequential one-pot reaction
      trifluoromethylation-etherification of the trifluoromethylcarbinol has been
      developed. Only one further one-pot reaction, ketal hydrolysis-oxidative
      cleavage, led to the final alpha-trifluoromethylated alpha-alkoxyaldehydes. This
      procedure was applied to the preparation of a series of enantiopure aryl,
      heteroaryl, and alkyl alpha-trifluoromethyl-alpha-alkoxyaldehydes.

PMID- 18816142
TI  - Self-assembly of quantum dots and carbon nanotubes for ultrasensitive DNA and
      antigen detection.
AB  - A highly selective, ultrasensitive, fluorescence detection method for DNA and
      antigen based on self-assembly of multiwalled carbon nanotubes (CNTs) and CdSe
      quantum dots (QDs) via oligonucleotide hybridization is reported.
      Mercaptoalkyloligonucleotide molecules bind to the quantum dots, while
      amineoalkyloligonucleotides bind to CNTs with -COCl surface groups. QDs and CNTs
      further assemble into nanohybrids through DNA hybridization in the presence of
      target complementary oligonucleotides. The method is achieved with good
      repeatability with the detection limit of 0.2 pM DNA molecules and 0.01 nM
      antigen molecules. This novel detection system can also be used for
      multicomponent detection and antigen-antibody immunoreaction. The novel system
      has great potential in applications such as ultrasensitive pathogen DNA or
      antigen or antibody detection, molecular imaging, and photoelectrical biosensors.

PMID- 18816143
TI  - Identification of recombinant equine growth hormone in horse plasma by LC-MS/MS:
      a confirmatory analysis in doping control.
AB  - Equine growth hormone (eGH) has been available since 1998 as an approved drug
      (EquiGen-5, Bresagen) containing recombinant eGH (reGH). It is suspected of being
      illegally administered to racehorses in order to improve physical performance and
      to speed-up wound healing. Thus it may be considered a doping agent which would
      require a sensitive and reliable method of identification and confirmation in
      order to regulate its use in racehorses. reGH differs from the native eGH by an
      additional methionine at the N-terminal (met-eGH) and has never been
      unambiguously detected in any type of biological matrix at trace concentrations
      (1-10 microg/L). A plasma sample (4 mL) was treated with ammonium sulfate at the
      reGH isoelectric point and the pellet was purified by solid-phase extraction.
      Specific peptides were generated by trypsin digestion and analyzed by LC-MS/MS.
      The detection limit was 1 microg/L. The method was validated according to
      European Union regulation (DEC/2002/657/EC) and the Association of Official
      Racing Chemists (AORC) requirements. Furthermore, it was successfully applied to
      determining the plasma concentrations of reGH with time using linear ion trap
      mass analyzer. The presence of this prohibited hormone (reGH) was also
      successfully detected by triple quadrupole mass spectrometry up to 48 h
      postadministration of reGH to a horse. The present LC-MS/MS method is the first
      with adequate sensitivity and specificity for detection of reGH, rbGH, and
      endogenous eGH. Hence, an efficient analytical tool is proposed as a means to
      fulfilling the regulation of reGH abuse in the horse racing industry.

PMID- 18816144
TI  - Singly bonded catenated germanes: eighty years of progress.

PMID- 18816146
TI  - Novel one-dimensional organometallic half metals: vanadium-cyclopentadienyl,
      vanadium-cyclopentadienyl-benzene, and vanadium-anthracene wires.
AB  - By using the density functional theory, we find that organometallic multidecker
      sandwich clusters V(2 n+1)Cp(2 n+2), Vn(FeCp2)(n+1) (Cp=cyclopentadienyl), and
      V(2n)Ant(n+1) (Ant=anthracene) may have linear structures, and their total
      magnetic moments generally increase with the cluster size. The one-dimensional
      (VCp)infinity, (VBzVCp)infinity (Bz=benzene), and (V2Ant)infinity wires are
      predicted to be ferromagnetic half-metals, while the one-dimensional
      (VCpFeCp)infinity wire is a ferromagnetic semiconductor. The spin transportation
      calculations show that the finite V2(n+1)Cp2(n+2) and Vn(FeCp2)(n+1) sandwich
      clusters coupled to gold electrodes are nearly perfect spin-filters.

PMID- 18816147
TI  - Biodegradable quantum dot nanocomposites enable live cell labeling and imaging of
      cytoplasmic targets.
AB  - Semiconductor quantum dots (QDs) offer great promise as the new generation of
      fluorescent probes to image and study biological processes. Despite their
      superior optical properties, QDs for live cell monitoring and tracking of
      cytoplasmic processes remain limited due to inefficient delivery methods
      available, altered state or function of cells during the delivery process and the
      requirement of surface-functionalized QDs for specific labeling of subcellular
      structures. Here, we present a noninvasive method to image subcellular structures
      in live cells using bioconjugated QD nanocomposites. By incorporating antibody
      coated QDs within biodegradable polymeric nanospheres, we have designed a
      bioresponsive delivery system that undergoes endolysosomal to cytosolic
      translocation via pH-dependent reversal of nanocomposite surface charge polarity.
      Upon entering the cytosol, the polymer nanospheres undergo hydrolysis thus
      releasing the QD bioconjugates. This approach facilitates multiplexed labeling of
      subcellular structures inside live cells without the requirement of cell fixation
      or membrane permeabilization. As compared to conventional intracellular delivery
      techniques, this approach allows the high throughput cytoplasmic delivery of QDs
      with minimal toxicity to the cell. More importantly, this development
      demonstrates an important rational strategy for the design of a multifunctional
      nanosystem for biological applications.

PMID- 18816145
TI  - Calcium orthophosphates: crystallization and dissolution.

PMID- 18816148
TI  - Low-temperature nanocrystal unification through rotations and relaxations probed
      by in situ transmission electron microscopy.
AB  - Through the mechanism of "oriented attachment", small nanocrystals can fuse into
      a wide variety of one- and two-dimensional nanostructures. This fusion phenomenon
      is investigated in detail by low-temperature annealing of a two-dimensional array
      of 10 nm-sized PbSe nanocrystals, in situ in the transmission electron
      microscope. We have revealed a complex chain of processes; after coalescence, the
      connected nanocrystals undergo consecutive rotations in three-dimensional space,
      followed by drastic interfacial relaxations whereby full fusion is obtained.

PMID- 18816149
TI  - Pain and the brain: diabetic neuropathic pain.
AB  - Pain and depression are commonly comorbid in primary care patients. This may be
      particularly true in patients experiencing diabetic peripheral neuropathic pain,
      a complication that affects many patients with diabetes in which nerve damage
      causes their pain perception to be enhanced. When treating patients who present
      with this type of pain or with generalized aches and pains, clinicians should be
      vigilant in inquiring about possible mood complaints that patients may be
      reticent to discuss. Some current antidepressant medications may be more
      effective in treating depression and comorbid pain than others.

PMID- 18816150
TI  - Treating depressive mixed States in bipolar disorders.
AB  - Although not recognized as a diagnostic entity in the DSM-IV-TR, mixed depression
      is a common clinical presentation. To treat depressive mixed states, clinicians
      in both Europe and the United States have developed valuable, yet different,
      therapeutic strategies. For example, the European model focuses on resolving
      patients' hypomanic symptoms, while the American model treats patients in
      depressive mixed episodes similarly to those who have bipolar II disorder. Common
      treatment practices between the 2 paradigms include the art of adopting
      pharmacotherapeutic regimens that are tailored to the needs of each patient and
      frequent evaluation of the patient's progress.

PMID- 18816151
TI  - Effect of hyperprolactinemia during development in children and adolescents.
AB  - Increased levels of prolactin associated with some antipsychotic treatment can
      potentially lead to serious adverse events including gynecomastia, galactorrhea,
      oligomenorrhea, amenorrhea, and pituitary tumors. Clinicians may need to employ
      pharmacotherapeutic interventions such as reducing dosage, switching
      antipsychotics, or prescribing adjunctive agents to minimize or prevent these
      negative side effects and improve patients' outcomes.

PMID- 18816152
TI  - Mentorship: the genuine article.

PMID- 18816153
TI  - The impact of mentorship.

PMID- 18816154
TI  - ADHD and comorbid disorders in adults.

PMID- 18816155
TI  - Who put the tyramine in Mrs. Murphy's fava bean?

PMID- 18816156
TI  - A randomized trial of brief cognitive-behavioral therapy for prevention of
      generalized anxiety disorder.

PMID- 18816157
TI  - Management of obsessive-compulsive disorder-related skin picking with gamma knife
      radiosurgical anterior capsulotomies: a case report.

PMID- 18816162
TI  - Ethical and practical issues associated with aggregating databases.

PMID- 18816163
TI  - Publication of clinical trials supporting successful new drug applications: a
      literature analysis.
AB  - BACKGROUND: The United States (US) Food and Drug Administration (FDA) approves
      new drugs based on sponsor-submitted clinical trials. The publication status of
      these trials in the medical literature and factors associated with publication
      have not been evaluated. We sought to determine the proportion of trials
      submitted to the FDA in support of newly approved drugs that are published in
      biomedical journals that a typical clinician, consumer, or policy maker living in
      the US would reasonably search. METHODS AND FINDINGS: We conducted a cohort study
      of trials supporting new drugs approved between 1998 and 2000, as described in
      FDA medical and statistical review documents and the FDA approved drug label. We
      determined publication status and time from approval to full publication in the
      medical literature at 2 and 5 y by searching PubMed and other databases through
      01 August 2006. We then evaluated trial characteristics associated with
      publication. We identified 909 trials supporting 90 approved drugs in the FDA
      reviews, of which 43% (394/909) were published. Among the subset of trials
      described in the FDA-approved drug label and classified as "pivotal trials" for
      our analysis, 76% (257/340) were published. In multivariable logistic regression
      for all trials 5 y postapproval, likelihood of publication correlated with
      statistically significant results (odds ratio [OR] 3.03, 95% confidence interval
      [CI] 1.78-5.17); larger sample sizes (OR 1.33 per 2-fold increase in sample size,
      95% CI 1.17-1.52); and pivotal status (OR 5.31, 95% CI 3.30-8.55). In
      multivariable logistic regression for only the pivotal trials 5 y postapproval,
      likelihood of publication correlated with statistically significant results (OR
      2.96, 95% CI 1.24-7.06) and larger sample sizes (OR 1.47 per 2-fold increase in
      sample size, 95% CI 1.15-1.88). Statistically significant results and larger
      sample sizes were also predictive of publication at 2 y postapproval and in
      multivariable Cox proportional models for all trials and the subset of pivotal
      trials. CONCLUSIONS: Over half of all supporting trials for FDA-approved drugs
      remained unpublished >/= 5 y after approval. Pivotal trials and trials with
      statistically significant results and larger sample sizes are more likely to be
      published. Selective reporting of trial results exists for commonly marketed
      drugs. Our data provide a baseline for evaluating publication bias as the new FDA
      Amendments Act comes into force mandating basic results reporting of clinical
      trials.

PMID- 18816164
TI  - Control of jasmonate biosynthesis and senescence by miR319 targets.
AB  - Considerable progress has been made in identifying the targets of plant
      microRNAs, many of which regulate the stability or translation of mRNAs that
      encode transcription factors involved in development. In most cases, it is
      unknown, however, which immediate transcriptional targets mediate downstream
      effects of the microRNA-regulated transcription factors. We identified a new
      process controlled by the miR319-regulated clade of TCP (TEOSINTE
      BRANCHED/CYCLOIDEA/PCF) transcription factor genes. In contrast to other miRNA
      targets, several of which modulate hormone responses, TCPs control biosynthesis
      of the hormone jasmonic acid. Furthermore, we demonstrate a previously
      unrecognized effect of TCPs on leaf senescence, a process in which jasmonic acid
      has been proposed to be a critical regulator. We propose that miR319-controlled
      TCP transcription factors coordinate two sequential processes in leaf
      development: leaf growth, which they negatively regulate, and leaf senescence,
      which they positively regulate.

PMID- 18816165
TI  - A mutual support mechanism through intercellular movement of CAPRICE and GLABRA3
      can pattern the Arabidopsis root epidermis.
AB  - The patterning of the Arabidopsis root epidermis depends on a genetic regulatory
      network that operates both within and between cells. Genetic studies have
      identified a number of key components of this network, but a clear picture of the
      functional logic of the network is lacking. Here, we integrate existing genetic
      and biochemical data in a mathematical model that allows us to explore both the
      sufficiency of known network interactions and the extent to which additional
      assumptions about the model can account for wild-type and mutant data. Our model
      shows that an existing hypothesis concerning the autoregulation of WEREWOLF does
      not account fully for the expression patterns of components of the network. We
      confirm the lack of WEREWOLF autoregulation experimentally in transgenic plants.
      Rather, our modelling suggests that patterning depends on the movement of the
      CAPRICE and GLABRA3 transcriptional regulators between epidermal cells. Our
      combined modelling and experimental studies show that WEREWOLF autoregulation
      does not contribute to the initial patterning of epidermal cell fates in the
      Arabidopsis seedling root. In contrast to a patterning mechanism relying on local
      activation, we propose a mechanism based on lateral inhibition with feedback. The
      active intercellular movements of proteins that are central to our model underlie
      a mechanism for pattern formation in planar groups of cells that is centred on
      the mutual support of two cell fates rather than on local activation and lateral
      inhibition.

PMID- 18816166
TI  - It's not how fat you are, it's what you do with it that counts.

PMID- 18816167
TI  - Advancing science through conversations: bridging the gap between blogs and the
      academy.

PMID- 18816168
TI  - Of mice and men, and chandeliers.
AB  - How does the human neocortex reliably propagate information through neural
      circuits? One mechanism appears to involve relying on strong connections from
      pyramidal neurons to interneurons and a depolarizing action of cortical
      chandelier cells.

PMID- 18816169
TI  - New source of muscle-derived stem cells with potential for alveolar bone
      reconstruction in cleft lip and/or palate patients.
AB  - Cleft lip and palate (CLP), one of the most frequent congenital malformations,
      affects the alveolar bone in the great majority of the cases, and the
      reconstruction of this defect still represents a challenge in the rehabilitation
      of these patients. One of the current most promising strategy to achieve this
      goal is the use of bone marrow stem cells (BMSC); however, isolation of BMSC or
      iliac bone, which is still the mostly used graft in the surgical repair of these
      patients, confers site morbidity to the donor. Therefore, in order to identify a
      new alternative source of stem cells with osteogenic potential without conferring
      morbidity to the donor, we have used orbicular oris muscle (OOM) fragments, which
      are regularly discarded during surgery repair (cheiloplasty) of CLP patients. We
      obtained cells from OOM fragments of four unrelated CLP patients (CLPMDSC) using
      previously described preplating technique. These cells, through flow cytometry
      analysis, were mainly positively marked for five mesenchymal stem cell antigens
      (CD29, CD90, CD105, SH3, and SH4), while negative for hematopoietic cell markers,
      CD14, CD34, CD45, and CD117, and for endothelial cell marker, CD31. After
      induction under appropriate cell culture conditions, these cells were capable to
      undergo chondrogenic, adipogenic, osteogenic, and skeletal muscle cell
      differentiation, as evidenced by immunohistochemistry. We also demonstrated that
      these cells together with a collagen membrane lead to bone tissue reconstruction
      in a critical-size cranial defects previously induced in nonimmunocompromised
      rats. The presence of human DNA in the new bone was confirmed by PCR with human
      specific primers and immunohistochemistry with human nuclei antibodies. In
      conclusion, we showed that cells from OOM have phenotypic and behavior
      characteristics similar to other adult stem cells, both in vitro and in vivo. Our
      findings suggest that these cells represent a promising source of stem cells for
      alveolar bone grafting treatment, particularly in young CLP patients.

PMID- 18816170
TI  - Three-dimensional synthetic niche components to control germ cell proliferation.
AB  - Spermatogonial stem cells (SSCs) are increasingly studied for potential use in
      tissue regeneration due to their ability to dedifferentiate into embryonic stem
      cell-like cells. For their successful therapeutic use, these cells must first be
      expanded in vitro using an appropriate culture system. We hypothesized that a
      hydrogel with proper biochemical and biomechanical properties may mimic the
      composition and structure of the native basement membrane onto which SSCs reside,
      thus allowing us to control SSC proliferation. This hypothesis was examined in
      two-dimensional (2D) and three-dimensional (3D) cultures using hydrogels formed
      from calcium cross-linked alginate molecules conjugated with synthetic
      oligopeptides containing the Arg-Gly-Asp sequence (RGD peptides). The RGD peptide
      density (N(RGD)) in gel matrices was controlled by mixing alginate molecules
      modified with RGD peptides and unmodified alginate molecules at varied ratios.
      The mechanical stiffness was controlled with the cross-linking density of gel
      matrices. Interestingly, the RGD peptide density modulated cell proliferation in
      both 2D and 3D cultures as well as the number and size of SSC colonies formed in
      3D cultures. In contrast, cell proliferation was minimally influenced by
      mechanical stiffness in 2D cultures. Overall, the results of this study elucidate
      an important factor regulating SSC proliferation and also present a bioactive
      hydrogel that can be used as a 3D synthetic basement membrane. In addition, the
      results of this study will be broadly useful in controlling the proliferation of
      various stem cells.

PMID- 18816171
TI  - Glutathione-S-transferase and microsomal epoxide hydrolase polymorphism and viral
      related hepatocellular carcinoma risk in India.
AB  - Hepatocellular carcinoma (HCC) is the fourth most common cancer worldwide, the
      main etiological factors being chronic infections with hepatitis B and C viruses.
      Genetic polymorphic forms of glutathione-S-transferase (GST) and microsomal
      epoxide hydrolase (mEPHX) have been associated with risk for various
      malignancies. The present study was undertaken to evaluate the association of
      GSTT1 and GSTM1 null genotypes and mEPHX polymorphisms with hepatitis virus
      related HCC risk in an Indian population. Three groups of subjects were
      considered, control (n = 169), chronic viral hepatitis (n = 174), and HCC (n =
      63). Polymerase chain reaction-restriction fragment length polymorphism (PCR
      RFLP) was used for this polymorphic study. Genotype distributions between
      categories were compared using the chi2 test; odds ratios (ORs) and 95%
      confidence interval were calculated to express the relative risk. GSTT1 null
      genotype was associated with 2.23-fold (p < 0.05) increased risk for HCC
      development as compared to the control group. However, GSTM1 null genotype was
      found to have a protective effect when hepatitis patients were considered. In
      case of mEPHX, R139R imposed a risk factor for HCC with both control (OR = 1.81)
      and chronic hepatitis-infected (OR = 2.06) subjects. Combination of heterozygous
      mutant genotypes at mEPHX exons 3 and 4 revealed a twofold risk (nonsignificant)
      for HCC. Further, combination of GSTM1 and T1 genotypes with either of exon 3 or
      4 polymorphism of mEPHX displayed synergistic associations (risk or protective)
      for HCC development. GST and mEPHX variants share a positive association with
      viral-related HCC risk in Indian population, although a larger sample size is
      still required to confirm the results.

PMID- 18816173
TI  - Abstracts from AIDS Vaccine 2008. Cape Town, South Africa. October 13-16, 2008.

PMID- 18816176
TI  - Thyrotoxicosis-induced ventricular arrhythmias.
AB  - BACKGROUND: Cardiac arrhythmias associated with thyrotoxicosis tend to be
      supraventricular in nature with atrial fibrillation being the most common.
      Ventricular arrhythmias are rarely associated with thyrotoxicosis and are
      considered to be secondary to intrinsic cardiac disease. SUMMARY: We present
      three patients with thyrotoxicosis and stable coronary disease in whom the
      primary cardiac rhythm disturbance was ventricular tachycardia. In all of these
      patients, the ventricular arrhythmias terminated with achievement of a euthyroid
      state. We hypothesize that the thyrotoxic state contributed to the etiology of,
      or lowered the threshold for the ventricular arrhythmias. CONCLUSION: Prompt
      attention to the management of thyrotoxicosis in patients with a history of
      significant heart disease is warranted in order to avoid potentially fatal
      arrhythmias.

PMID- 18816177
TI  - Thyroid hormone resistance and pituitary enlargement after thyroid ablation in a
      woman on levothyroxine treatment.
AB  - We report a patient with inappropriate secretion of thyrotropin (TSH) and a
      pituitary mass. Although she had been treated for biochemical hyperthyroidism
      with thyroid surgery and radioiodine ablation, she had never complained of
      specific symptoms or demonstrated signs of overt thyroid dysfunction. On
      evaluation, she had increased free thyroxine and TSH levels, normal serum
      glycoprotein alpha-subunit levels, and a significant TSH over-response to
      exogenous thyrotropin-releasing hormone stimulation. Magnetic resonance imaging
      with gadolinium enhancement showed a pituitary enlargement with suprasellar
      extension. An indium In 111 pentetreotide scan showed an abnormal focus of
      radionuclide accumulation in the pituitary area. Sequencing of the TRbeta gene
      showed that the patient was heterozygous for a new single nucleotide substitution
      resulting in the replacement of the normal arginine with a serine at amino acid
      320 (R320S). We review the difficulties encountered in establishing a correct
      diagnosis in patients with inappropriate secretion of TSH in combination with
      pituitary enlargement. Due to its possible false-negative results, we do not
      recommend the use of indium In 111 pentetreotide as a tool in the differential
      diagnosis of inappropriate secretion of TSH.

PMID- 18816178
TI  - Thyroid function and exposure to styrene.
AB  - BACKGROUND: Many natural substances and drugs have long been known to cause
      goiter or thyroid dysfunction. More recently, several environmental pollutants,
      such as pesticides and industrial compounds, have been investigated for their
      thyroid-disrupting activity and related adverse effects on human health. The aim
      of this study was to evaluate the effects of styrene on the thyroid axis in
      occupationally exposed workers. METHODS: Thirty-eight exposed (E) and 123
      nonexposed (NE) male workers (controls) were assessed. Serum concentrations of
      thyrotropin (TSH; basal and after thyrotropin-releasing hormone [TRH]
      administration.), free thyroxine (FT(4)), free triiodothyronine (FT(3)), anti
      thyroglobulin, thyroid peroxidase antibody, and calcitonin were measured. Thyroid
      ultrasound examination was also performed. In E workers, urinary creatinine,
      mandelic acid (MA), and phenylglyoxylic acid (PGA) were also measured. RESULTS:
      No significant differences between E and NE workers were demonstrated, as far as
      thyroid volume, nodularity, serum thyroid antibodies, and calcitonin were
      analyzed. However, in the E group a positive correlation between duration of
      exposure and thyroid volume was detected. After exclusion of subjects with
      nodular or autoimmune thyroid diseases, serum concentrations of FT(4), FT(3), and
      TSH did not differ between the two groups. In E workers there was a positive
      correlation between the urinary concentrations of styrene metabolites (MA plus
      PGA) and FT(4) or FT(4)/FT(3) ratio (p < 0.05; r = 0.45 and p < 0.005; r = 0.61,
      respectively), while no correlation was observed between urinary concentrations
      of MA plus PGA and serum TSH (either basal and stimulated). CONCLUSIONS: Chronic
      exposure to styrene is not associated with an increase in nodular or autoimmune
      thyroid diseases. However, styrene could interfere with peripheral metabolism of
      thyroid hormones by inhibiting T(4) to T(3) conversion. Whether this is a direct
      effect on iodothyronine deiodinases or a consequence of a general distress, such
      as in nonthyroidal illnesses, remains to be established. Further studies in a
      larger population of exposed workers are needed to confirm these preliminary
      observations.

PMID- 18816179
TI  - Radiofrequency ablation of hepatic metastases from thyroid carcinoma.
AB  - BACKGROUND: Radiofrequency ablation (RFA) is performed for various types of liver
      tumors. It might also have a role in the palliative treatment of liver metastases
      from thyroid carcinoma. SUMMARY: Three patients with liver metastases of thyroid
      carcinoma were retrieved from our database of 125 patients who had been treated
      with RFA for liver tumors. In all three patients, the metastases were a sign of
      widespread disease, and several other treatment modalities had been performed
      earlier. Two patients had metastases from medullary thyroid carcinoma and had
      severe diarrhea. The third patient had a rapidly progressive metastasis of a
      follicular thyroid carcinoma. The aim of the treatment was cytoreduction with
      amelioration of symptoms (n = 2) and debulking with increased sensitivity for
      subsequent (131)I treatment. The ablation was performed via laparotomy (n = 1),
      laparoscopically (n = 1), or percutaneously (n = 1). One patient experienced
      superficial burn wounds after a long-lasting RFA procedure. Severity of symptoms
      was reduced significantly after RFA for a prolonged period of time. RFA induced
      partial tumor necrosis because of hypervascularization of the tumor in one
      patient. After arterial embolization the second RFA treatment induced total tumor
      necrosis. Local recurrences at the site of the ablated liver metastases were not
      encountered during follow-up. CONCLUSIONS: RFA is a useful treatment modality in
      patients with liver metastases from thyroid carcinoma. It should be considered an
      adjunct to other types of treatment or for those patients in whom more regular
      treatment modalities are not effective or possible or are associated with
      increased risks.

PMID- 18816180
TI  - Type 3 deiodinase is highly expressed in infiltrating neutrophilic granulocytes
      in response to acute bacterial infection.
AB  - BACKGROUND: Macrophages and polymorphonuclear cells (PMNs) play an important role
      in the first line of defense against bacteria by infiltrating the infected organ
      in order to clear the harmful pathogen. Our earlier studies showed that
      granulocytes express type 3 deiodinase (D3) when activated during a turpentine
      induced abscess. We hypothesized that D3 expression by granulocytes may also
      occur during bacterial infection. METHODS: In order to test this hypothesis, we
      used the following experimental infection models: peritonitis induced by
      Escherichia coli and acute pneumonia induced by Streptococcus pneumoniae.
      RESULTS: E. coli-induced peritonitis was characterized by infiltration in the
      liver by inflammatory cells with abundant immunocytochemical D3 expression while
      no staining was present in hepatocytes of infected or control mice. Acute
      pneumonia induced by S. pneumoniae resulted in inflamed lungs characterized by
      numerous infiltrating granulocytes expressing D3 while no D3 staining was present
      in lung sections without an infiltrate. Serum thyroid hormones were negatively
      correlated to bacterial outgrowth in both lung and spleen, and thus to the
      severity of illness. CONCLUSION: Infiltrating granulocytes during acute bacterial
      infection express D3. Our work supports the hypothesis that D3 plays an important
      role during chemical and bacterial inflammation. Whether the resulting decreased
      local bioavailability of thyroid hormones or rather the increased local
      availability of iodide is an important element of the innate immune response
      remains to be studied.

PMID- 18816181
TI  - Dramatic response to cholestyramine in a patient with Graves' disease resistant
      to conventional therapy.
AB  - BACKGROUND: Resistance to the conventional treatment of hyperthyroidism with
      antithyroid drugs is not commonly found in clinical practice, and only few other
      treatment options have been reported on in detail. For example, surgery or
      radioiodine ablation are well-accepted interventions that must be always
      considered. The euthyroid state is strongly recommended before both of these as
      this might reduce complications. There are few studies indicating that bile acid
      sequestrants, when added to antithyroid drugs, produce a more rapid decline in
      serum thyroid hormone levels and that this effect is maintained for at least 4
      weeks. Complete normalization of serum thyroid hormone levels is generally not
      expected, however. SUMMARY: We report a patient whose thyrotoxicosis failed to
      respond to conventional treatment. The patient remained persistently
      hyperthyroid, both clinically and biochemically, despite several months of
      methimazole and propranolol and the addition of iodine. Cholestyramine, a bile
      acid sequestrant, was then added, and a dramatic improvement was observed.
      CONCLUSION: We report a patient who was resistant to conventional antithyroid
      drugs in whom thyroid hormone levels completely normalized after 1 week of
      additional treatment with cholestyramine.

PMID- 18816182
TI  - Antithyroid drug-induced aplastic anemia.
AB  - BACKGROUND: Antithyroid drugs have been used for more than 50 years for the
      management of hyperthyroidism. Most patients tolerate treatment well but some may
      develop life threatening side effects such as agranulocytosis and aplastic anemia
      (AA). We review all cases of antithyroid drug induced AA and describe, as
      illustrative cases, two women with Graves' disease who developed AA after 8 and
      24 weeks of carbimazole (CBM) and methimazole (MMI) treatment respectively.
      PATIENT FINDINGS AND SUMMARY: To date, at least 34 cases of aplastic anemia (AA)
      due to antithyroid drugs [(1 with CMZ, 31 with MMI, and 2 with propylthiouracil
      (PTU)] have been published, not including the two patients described here. In
      addition, at least another 14 patients in whom AA developed after treatment with
      antithyroid drugs (11 with CMZ, and 3 with MMI) have been reported in Yellow Card
      Scheme data analysis. Patients with AA usually exhibit sudden onset of symptoms
      after a relative short time of exposure to the drugs, and all have concomitant
      agranulocytosis. Most have a rapid recovery following discontinuation of the drug
      and supportive treatment. Although only two antithyroid drug induced AA deaths
      have been published, the mortality rate was higher in the Yellow Card Scheme data
      analysis. CONCLUSIONS: Aplastic anemia associated with antithyroid drug treatment
      is rarer than antithyroid drug associated agranulocytosis. The prognosis of
      patients with antithyroid drug induced AA is good overall, but may not be as
      favorable as that of antithyroid drug induced isolated agranulocytosis.

PMID- 18816183
TI  - Differentiating alternative splice variant patterns of human telomerase reverse
      transcriptase in thyroid neoplasms.
AB  - BACKGROUND: Although fine-needle aspiration (FNA) biopsy of thyroid nodules is
      very sensitive in detecting thyroid malignancy, it remains ambiguous in 20-30% of
      cases. Current biomarkers for thyroid cancer lack either the sensitivity or
      specificity to substantially address this clinical problem. The aim of this study
      was to investigate the gene expression patterns of human telomerase reverse
      transcriptase (hTERT) alternative splice variants in benign and malignant thyroid
      tumors in an attempt to find a more reliable biomarker in the differential
      diagnosis of thyroid nodules. METHODS: One hundred and thirty-three thyroid
      tumors from eight histopathological tumor types were collected from patients
      undergoing thyroid surgery at Johns Hopkins Hospital. Gene expression patterns of
      hTERT alternative splice variants were investigated in the tumors by nested
      reverse transcriptase-PCR. Telomerase enzyme activity was evaluated in a subset
      of 16 samples associated with the different hTERT patterns. Association of c-myc
      expression and hTERT patterns was also examined. RESULTS: Malignant thyroid
      tumors exhibited a greater proportion of the active full-length hTERT transcript
      (0.57 +/- 0.15) than inactive splice variants, alpha(-) (0.13 +/- 0.02), or beta(
      )/alpha(-)beta(-) deletion transcripts (0.30 +/- 0.11; p < 0.001). The opposite
      was observed in benign tumors, which exhibited greater proportions of beta(
      )/alpha(-)beta(-) deletion transcripts (0.64 +/- 0.08) than either the full
      length (0.19 +/- 0.06) or alpha(-) deletion transcripts (0.17 +/- 0.02; p <
      0.001). Similar results were observed among a diagnostically challenging subset
      of 50 thyroid tumors that were suspicious for malignancy on FNA. Further,
      increased telomerase enzymatic activity was only associated with expression of
      the full-length hTERT isoform. In contrast, c-myc expression, which has been
      implicated in hTERT regulation, correlated with overall hTERT transcription
      without specificity for expression of the full-length isoform. CONCLUSIONS: These
      differences in gene expression patterns of hTERT alternative splice variants may
      provide a useful adjunct to FNA diagnosis of suspicious thyroid tumors.

PMID- 18816184
TI  - Predictive value of recombinant human TSH stimulation and neck ultrasonography in
      differentiated thyroid cancer patients.
AB  - BACKGROUND: Serum thyroglobulin (Tg) stimulation by recombinant human TSH
      (rhTSH), in combination with neck ultrasonography (US), is an important tool in
      the first follow-up of differentiated epithelial cell thyroid carcinoma (DTC)
      patients. The objective of this study was to investigate if a second rhTSH
      stimulation, performed 2-3 years later, is of clinical utility in the follow-up
      of these patients. METHODS: One hundred and one consecutive ambulatory DTC
      patients were studied. The great majority of them (89/101) were low-risk
      patients, being stage I or II at tumor node metastasis (TNM) staging
      classification. All study patients had been treated by surgery and radioiodine
      ablation, and exhibited, at first rhTSH follow-up, either undetectable Tg (<or=1
      ng/mL) (rhTSH1-Tg-, n = 89 patients considered as free of disease) or low Tg (>1
      5 ng/mL) (rhTSH1-Tg+, n = 12 patients considered with uncertain prognosis), with
      no US evidence of residual disease. In all patients, serum Tg measurement after a
      second rhTSH stimulation and neck US were performed. RESULTS: At the second
      follow-up, all 89 rhTSH1-Tg-patients showed a negative US, and Tg became low
      positive only in one case, whereas it remained undetectable in the other
      patients. The overall negative predictive value of rhTSH1-Tg- was, then, 98.9%.
      Out of the remaining 12 patients (i.e., rhTSH1-Tg+ patients), 2 showed disease
      persistence/recurrence (with a positive predictive value of rhTSH1-Tg+ of 16.7%)
      and 6 became Tg-. CONCLUSIONS: A second rhTSH stimulation is useless in DTC
      patients who were rhTSH-Tg and imaging negative at first follow-up, while it is
      suggested in patients with detectable, although low, rhTSH-Tg levels at first
      follow-up: in the absence of clinical or US evidence of disease persistence,
      these patients should not be retreated by radioiodine, but simply scheduled for a
      later rhTSH stimulation.

PMID- 18816185
TI  - Cross-talk between pulmonary injury, oxidant stress, and gap junctional
      communication.
AB  - Gap junction channels interconnect several different types of cells in the lung,
      ranging from the alveolar epithelium to the pulmonary vasculature, each of which
      expresses a unique subset of gap junction proteins (connexins). Major lung
      functions regulated by gap junctional communication include coordination of
      ciliary beat frequency and inflammation. Gap junctions help enable the alveolus
      to regulate surfactant secretion as an integrated system, in which type I cells
      act as mechanical sensors that transmit calcium transients to type II cells.
      Thus, disruption of epithelial gap junctional communication, particularly during
      acute lung injury, can interfere with these processes and increase the severity
      of injury. Consistent with this, connexin expression is altered during lung
      injury, and connexin-deficiency has a negative impact on the injury response and
      lung-growth control. It has recently been shown that alcohol abuse is a
      significant risk factor associated with acute respiratory distress syndrome.
      Oxidant stress and hormone-signaling cascades in the lung induced by prolonged
      alcohol ingestion are discussed, as well as the effects of these pathways on
      connexin expression and function.

PMID- 18816187
TI  - Materials in surgery: a review of biomaterials in postsurgical tissue adhesion
      and seroma prevention.
AB  - Postoperative tissue adhesion is a complex inflammatory disorder in which tissues
      that normally remain separated in the body grow into each other. Seroma is a
      common postoperative complication that arises when serous fluid collects in the
      space generated following surgeries that require extensive dissection and that
      create large empty spaces. Postsurgical tissue adhesion and seroma formation are
      two serious surgical complications that have received more attention recently
      from the biomaterials community. This paper provides a review of the pathogenesis
      and treatment of these surgical complications, with a thorough overview of
      biomaterial-based treatment and prevention methods.

PMID- 18816188
TI  - A simplified and standardized polymerase chain reaction format for the diagnosis
      of leishmaniasis.
AB  - BACKGROUND: Definite diagnosis of Leishmania infections is based on demonstration
      of the parasite by microscopic analysis of tissue biopsy specimens or aspirate
      samples. However, microscopy generally shows low sensitivity and requires
      invasive sampling. METHODS: We describe here the development of a simple and
      rapid test for the detection of polymerase chain reaction-amplified Leishmania
      DNA. A phase 1 evaluation of the text was conducted in clinical samples from 60
      nonendemic and 45 endemic control subjects and from 44 patients with confirmed
      cutaneous leishmaniasis (CL), 12 with mucocutaneous leishmaniasis (MCL), and 43
      with visceral leishmaniasis (VL) from Peru, Kenya, and Sudan. RESULTS: The lower
      detection limits of the assay are 10 fg of Leishmania DNA and 1 parasite in 180
      microL of blood. The specificity was 98.3% (95% confidence interval [CI], 91.1%
      99.7%) and 95.6% (95% CI, 85.2%-98.8%) for nonendemic and endemic control
      samples, respectively, and the sensitivity was 93.2% (95% CI, 81.8%-97.7%), 91.7%
      (95% CI, 64.6%-98.5%), and 86% (95% CI, 72.7%-93.4%) for lesions from patients
      with CL or MCL and blood from patients with VL, respectively. CONCLUSIONS: The
      Leishmania OligoC-TesT showed high specificity and sensitivity in clinical
      samples and was able to detect the parasite in samples obtained by less invasive
      means, such as blood, lymph, and lesion scrapings. The assay is a promising new
      tool for simplified and standardized molecular detection of Leishmania parasites.

PMID- 18816189
TI  - Interleukin-12p70 deficiency increases survival and diminishes pathology in
      Trypanosoma congolense infection.
AB  - To determine the immunological role played by interleukin (IL)-12 family members
      in Trypanosoma congolense infection, IL-12p35(-/-), IL-12p40(-/-), and IL-12p35(
      /-)/p40(-/-) mice were used. While the latter 2 strains lack all IL-12
      homologues, IL-12p35(-/-) mice still produce IL-12p80 homodimers and IL-23.
      Compared with wild-type mice, all infected IL-12-deficient mouse strains showed
      prolonged survival, whereas parasitemia levels were unaltered. Interferon (IFN)
      gamma production in IL-12-deficient mice was strikingly reduced during the acute
      and chronic stages of infection, coinciding with significantly reduced chronic
      stage hepatocellular damage, as demonstrated by histological analysis and plasma
      aspartate transaminase measurements. In contrast, IL-10 production was not
      affected by the absence of IL-12. Taken together, these results show that, during
      T. congolense infection, the absence of IL-12, but not the IL-12p80 homodimer or
      IL-23, leads to a reduction in IFN-gamma production, which reduces hepatic
      pathology and improves host survival in conjunction with IL-10 without negatively
      affecting parasitemia control.

PMID- 18816186
TI  - Modulation of brain hemichannels and gap junction channels by pro-inflammatory
      agents and their possible role in neurodegeneration.
AB  - In normal brain, neurons, astrocytes, and oligodendrocytes, the most abundant and
      active cells express pannexins and connexins, protein subunits of two families
      forming membrane channels. Most available evidence indicates that in mammals
      endogenously expressed pannexins form only hemichannels and connexins form both
      gap junction channels and hemichannels. Whereas gap junction channels connect the
      cytoplasm of contacting cells and coordinate electric and metabolic activity,
      hemichannels communicate the intra- and extracellular compartments and serve as a
      diffusional pathway for ions and small molecules. A subthreshold stimulation by
      acute pathological threatening conditions (e.g., global ischemia subthreshold for
      cell death) enhances neuronal Cx36 and glial Cx43 hemichannel activity, favoring
      ATP release and generation of preconditioning. If the stimulus is sufficiently
      deleterious, microglia become overactivated and release bioactive molecules that
      increase the activity of hemichannels and reduce gap junctional communication in
      astroglial networks, depriving neurons of astrocytic protective functions, and
      further reducing neuronal viability. Continuous glial activation triggered by low
      levels of anomalous proteins expressed in several neurodegenerative diseases
      induce glial hemichannel and gap junction channel disorders similar to those of
      acute inflammatory responses triggered by ischemia or infectious diseases. These
      changes are likely to occur in diverse cell types of the CNS and contribute to
      neurodegeneration during inflammatory process.

PMID- 18816190
TI  - Intracellular survival of Leishmania species that cause visceral leishmaniasis is
      significantly reduced by HIV-1 protease inhibitors.
AB  - Visceral leishmaniasis is now recognized as an opportunistic disease in
      individuals infected with human immunodeficiency virus type 1 (HIV-1). Although
      the usefulness of HIV-1 protease inhibitors (PIs) in antiretroviral regimens is
      well documented, little is known about their potential impact in the setting of
      Leishmania/HIV-1 coinfections. We now report that, although selected PIs do not
      inhibit the growth of Leishmania infantum promastigotes alone in culture, these
      drugs significantly inhibit the intracellular survival of parasites in phorbol
      myristate acetate-differentiated THP-1 macrophages and human primary monocyte
      derived macrophages (MDMs). Furthermore, a field isolate of Leishmania donovani
      resistant to sodium stibogluconate (SbV), one of the drugs most commonly used to
      treat leishmaniasis, is equally susceptible to the tested PIs compared with a
      sensitive strain, thus suggesting that resistance to SbV does not result in cross
      resistance to PIs. Importantly, the efficacy of PIs to reduce the intracellular
      growth of Leishmania parasites is also observed in MDMs coinfected with HIV-1.

PMID- 18816191
TI  - Progressive telomere shortening of Epstein-Barr virus-specific memory T cells
      during HIV infection: contributor to exhaustion?
AB  - Individuals infected with human immunodeficiency virus (HIV) have low numbers of
      functional Epstein-Barr virus (EBV)-specific CD8+ T cells in the face of a high
      EBV load, suggesting that these cells have become exhausted. We investigated
      whether the observed chronic EBV loads during HIV infection could cause
      exhaustion of EBV-specific T cells by using flow-FISH (flow cytometry in
      combination with fluorescence in situ hybridization) to analyze the telomere
      length of EBV-specific CD8+ T cells. Enhanced telomere shortening of EBV-specific
      T cells was observed during HIV infection, compared with the decline in telomere
      length observed in the CD8+ T cells of healthy subjects. Thus, chronic exposure
      to high antigen levels may lead to the progressive shortening of telomeres of
      antigen-specific T cells, which may impair viral control.

PMID- 18816192
TI  - The theoretical influence of immunity between strain groups on the progression of
      drug-resistant tuberculosis epidemics.
AB  - BACKGROUND: Emerging research suggests that genetically distinct strains of
      Mycobacterium tuberculosis may modulate the immune system differently. This may
      be of importance in high-burden settings where > or =1 genetic group of M.
      tuberculosis confers significant morbidity. METHODS: A dynamic mathematical model
      was constructed to evaluate how different degrees of cross-immunity among M.
      tuberculosis groups could affect epidemics of drug-resistant tuberculosis (TB).
      RESULTS: Simulated populations with immunogenically distinct TB strain groups
      experienced a heightened risk of drug-resistant TB, compared with populations
      without such strain diversity, even when the same rates of case detection and
      treatment success were achieved. The highest risks of infection were observed in
      populations in which HIV was prevalent. Drug-resistant strains with very low
      transmission fitness could still propagate in environments with reduced cross
      immunity among different strain groups, even after common targets for case
      detection and treatment success are reached. CONCLUSIONS: It is possible that the
      propagation of drug-resistant strains could depend not only on the rate of
      development of resistance and the fitness of the drug-resistant strains but,
      also, on the diversity of the strains in the region. The risk of infection with
      drug-resistant strains could be amplified in locations where there is reduced
      cross-immunity between originating strain groups. This amplification may be most
      profound during the first few decades of TB treatment expansion.

PMID- 18816198
TI  - Introduction: Fifth Annual NIH Interdisciplinary Women's Health Research
      Symposium, November 19, 2008.

PMID- 18816202
TI  - Preferences and perceived barriers to treatment for depression during the
      perinatal period.
AB  - BACKGROUND AND METHODS: Little is understood about why few women during the
      perinatal period will use depression treatment. In particular, beliefs and
      barriers related to depression treatment use have not been studied. In this
      study, African American and white pregnant women (n = 108) who screened > or =10
      on the Edinburgh Postnatal Depression Scale (EPDS) were asked about recent formal
      and informal treatment use in prenatal care settings. Confidence in the
      helpfulness of treatment, providers, and settings and perceived barriers to
      treatment were assessed and compared between African American and white women.
      RESULTS: Pregnant women overall reported low rates of formal treatment use but
      frequently sought help from informal sources, such as friends, family, and
      printed materials. All women expressed greatest confidence in psychosocial
      treatments and lowest confidence in antidepressants. African American women
      reported less confidence in advice from family and friends and in antidepressants
      than did white women. Women expressed greatest confidence in treatments delivered
      by mental health professionals and religious leaders. African American women
      sought help more frequently and had significantly more confidence in religious
      leaders as treatment deliverers than white women. Women had greatest confidence
      in treatments delivered in professional and home settings, with African American
      women expressing greater confidence in religious settings than white women. All
      women reported greatest concern with structural barriers, compared with
      attitudinal and knowledge barriers. CONCLUSIONS: Understanding patterns of
      treatment use, beliefs, and barriers to depression treatment provides important
      information for tailoring and improving appropriate use of mental health
      treatment in women during the perinatal period.

PMID- 18816204
TI  - [The essential role of water treatment system (WTS) in the qualify of water for
      hemodialysis].

PMID- 18816205
TI  - [HIV and dialysis: unfounded optimism or real change].

PMID- 18816206
TI  - [The role of immunocompetent cell renal infiltration in the pathogenesis of
      arterial hypertension].

PMID- 18816207
TI  - [Monitoring on-line treated water and dialysate quality].
AB  - INTRODUCTION: On line-treated water has been designed to obtain ultrapure water.
      This quality of water is obviously necessary to obtain ultrapure dialysate,
      although this is not the only condition. To keep the quality of the process, is
      necessary the continuous monitoring of the water treatment, dialysate and
      haemodialysis machines. METHOD: After the installation of a water treatment with
      these characteristics, we developed a protocol to follow up its quality. The
      measures included in the protocol were: a) Microbiologic, endotoxin and chemical
      controls of the water on different stage: before and at the end of the treatment,
      pre-treatment and network of distribution. The chemical analysis included
      analytical and colorimetric measures. b) Control of specific mechanical functions
      of the facilities. c) Microbiologic and endotoxin analysis of the dialysate
      produced by haemodialysis machines. d) Control and maintenance of haemodialysis
      machines, according to the technical indications. RESULTS: We analyse the initial
      five years of water treatment with the aim to evaluate quality parameters and
      efficiency. We explain the reasons of the modifications introduced in the system.
      During this period we have not any episodes of global or partial contamination.
      We refer here some incidents related with the quality of raw water supply before
      the treatment, but in any case it was necessary neither to stop the water supply
      or to reduce the water quality. We observed a persistent contamination of one
      haemodialysis monitor due to the port used to get the samples. CONCLUSIONS: On
      line-treated water is at present the most appropriate system to obtain high
      quality water for haemodialysis. The process must be continuously monitored
      through specific protocols developed to evaluate the raw water's characteristics
      and the treated water.

PMID- 18816208
TI  - [Outcome of HIV-infected patients of peritoneal dialysis: experience in a center
      and literature review].
AB  - Overall survival of HIV-infected has increased over the last ten years. In
      parallel a higher need for renal replacement therapy (RRT) in this population has
      been more observed. RRT associated complications and outcomes greatly varied
      since the introduction of highly active antiretroviral therapy (HAART) and scarce
      data is available regarding the outcome of peritoneal dialysis (PD) in HIV
      infected patients under HAART. We described 8 HIV-infected patients who were
      admitted at the Peritoneal Dialysis Unit at our institution from November-95 to
      November-07. Mean age was 40.7 +/- 5.3. Causes of end-stage renal disease were
      diabetes mellitus type 1 (2), focal and segmental glomerular sclerosis (2), IgA
      nephropathy (1) and unknown origin (3). High blood pressure was detected in 62,5%
      of the patients. Mean follow-up was 41.2 +/- 32.1 months (range 12-103). One, two
      and three year survival was 100, 62.5 and 50% respectively. Overall mortality was
      62.5% and cardio-vascular events were the main cause of death (2 patients, 25%).
      Infective peritonitis rate was 0.36 IP/year, and Staphylococcus epidermidis was
      the most common pathogen identified. Hospital admission rate was 0.69
      admission/year and the main cause of admission was respiratory tract infection.
      All patients received HAART. Lamivudine, stavudine and nelfinavir were the most
      frequent treatment prescribed. During the first year in PD undetectable viral
      load and CD4 % were not modified. A significant weight gain was observed during
      the first year of the study (60.6 kg. vs 64.9 kg. p > or = 0.016). Our results
      suggest that PD is a suitable choice for RRT in HIV-infected. Compared to
      previous studies, an increase in overall survival and a decrease in PD-associated
      complications were seen. The significance of cardio-vascular risk factors in the
      outcome of PD in HIV-infected patients is not completely determined. A
      multidisciplinary approach and a management of patients in individual basis
      remains mandatory.

PMID- 18816209
TI  - [Is Cinacalcet a cost-effective treatment in severe secondary hyperparathyroidism
      in patients on hemodialysis?].
AB  - BACKGROUND: A previous study using cinacalcet, as compared to vitamin D alone,
      showed a better reduction response of PTH levels and a significant diminution of
      secondary effects. The objective of present study was to evaluate the additional
      cost of adding cinacalcet to the standard treatment of patients with severe
      secondary hyperparathyroidism (SHPT) taking into account the treatment goals
      achieved. METHODS: 12 month prospective study of 23 patients with severe SHPT.
      Two treatment regimens were considered: standard treatment (m 0) and standard
      treatment plus cinacalcet (m 12). Four consequences of inadequate control of SHPT
      were registered: parathiroid hormone (PTH), Calcium (Ca), Phosphorus (P) and the
      Ca x P product serum levels. Treatment effectiveness was measured as percentage
      of patients who achieved treatment goal according to each indicator: PTH < 800
      pg/mL, PTH between 150 and 300 pg/mL, Calcium < 9.5 mg/dL, Phosphorus < 5.5
      mg/dL, and Ca x P product < 55. Annual and monthly costs were calculated for both
      treatment regimens using Spanish 2007 tariffs, and taking into account the dose
      reduction in some other treatments. Results are presented as incremental costs
      and cost per patient who achieved treatment goal. RESULTS: At 12 month it was
      observed a higher percentage of patients who achieved simultaneously the 4
      therapeutic goals with respect to basal moment, from 0% to 52.1%. Cinacalcet
      allowed to save costs in concomitant drugs, achieving a total saving of 149 euros
      per patient and month. At 12 month, Cinacalcet achieved a reduction of percentage
      of patients with PTH > 800 pgr/mL with half of costs than standard treatment
      (651.35 euros vs 1363.68 euros). It was not possible to calculate the cost for
      PTH indicator since at the study onset, there was no patient who achieved a level
      between 150 and 300 pg/mL. Cinacalcet allowed reaching treatment goals in
      Calcium, Phosphorus and Ca x P product in a more cost-effective way (2164.2 euros
      vs 2684.8 euros). CONCLUSIONS: Although Cinacalcet is expensive,p atients treated
      with Cinacalcet showed a minor cost per patient who achieved treatment goal than
      patients without Cinacalcet. The ability of cinacalcet to reduce PTH secretion,
      along with the reductions in the serum Ca, P, and Ca x P product, provides an
      alternative to the traditional treatment paradigm, and should be a welcomed
      addition in the management of SHPT.

PMID- 18816210
TI  - [Reduced nocturnal systolic blood pressure dip in obese children].
AB  - Ambulatory blood pressure monitoring (ABPM) allows evaluation not only of casual
      daytime elevations of blood pressure (BP) but also alterations in the 24-hour
      circadian patterns of BP. The aim of the present study was to assess 24-hour BP
      patterns in a population of obese children who were referred to our outpatient
      clinic, in relation to the degree of obesity, body fat distribution and insulin
      resistance, and considering other cardiovascular risk factors. METHODS: Office
      and ambulatory BP measurements, and fasting serum glucose, insulin and HOMA
      determinations were obtained in 119 obese children (7-15 years old). Urinary
      albumin excretion was measured in the first morning urine. The extend of obesity
      was quantified using body mass index z score adjusted by age and gender. RESULTS:
      The prevalence of office hypertension in only one set of blood pressure
      measurements was 47%. This value was not confirmed on further separate occasions.
      The prevalence of global ambulatory hypertension was 36%. Diurnal systolic
      hypertension was found in 14%, while 39 patients (33%) had nocturnal systolic
      hypertension. Twenty five of them (64%) were only hypertensive at nightime and
      the rest (n = 14), were also hypertensive during the day. Only 4 patients were
      exclusively systolic hypertensive at daytime (table III). None of the patients
      were exclusively diastolic at day or nighttime. Of the total 119 subjects 47% non
      systolic dippers. This abnormal BP pattern was associated with the degree of
      obesity (p < 0.001) and insulinresistance (HOMA values; p < 0.001). The
      anthropometric and metabolic characteristics of the population studied are shown
      in table I and II respectively. The correlations coefficients and regression
      analysis between anthropometric and metabolic parameters are shown in table IV
      and V. CONCLUSION: Reduced nocturnal systolic blood pressure dip and nightime
      systolic hypertension were the most frequent forms of hypertension in our cohort
      of severe obese children. These alterations in the 24-hour circadian patterns of
      BP were related to the degree of obesity and insulin resistance.

PMID- 18816211
TI  - [Renal involvement in benign monoclonal gammopathies: an underdiagnosed
      condition].
AB  - Renal involvement is observed frequently in association with malignant
      gammopathies, mainly those related to light chain deposition, although has also
      been described in non-malignant monoclonal gammopathy. This study reports the
      clinicopathological findings and outcome in 9 patients with nephropaty secondary
      to monoclonal immunoglobulin deposit in absence of malignancy. They were three
      men and six women and they were 59.2+/-12 years old. All patients presented
      proteinuria and different levels of renal insufficiency (mean creatinin = 315+/
      187 micromol/L) at the moment of diagnostic. Two patients required dialysis at
      the time of renal biopsy. The pathology studies revealed a nodular sclerosing
      glomerulopathy in four cases, mesangiocapilary glomerulonephritis in three cases,
      only tubular lesions in one and mesangial lesions in the other one. The treatment
      applied was: Prednisone alone (two cases), with chemotherapy associated (melfalan
      in two, clorambucil in one and ciclophosphamide in another one). One patient
      received plasmapheresis and mycophenolate and another patient undergone a bone
      marrow authotransplant associated to mycophenolate and prednisone. One of the two
      patients who required dialysis at the moment of presentation was not treated.
      After a follow-up of more than 4 years (4.89 +/-DE: 3.69) renal function improved
      or remained stable in three patients and proteinuria was disappeared in more than
      50% of patients. Four patients had a worsening of renal function and they
      required dialysis during the time of follow-up (in 2,4 years +/- DE: 4,3). In any
      case malignitation was observed. Chemotherapy stabilized or improved renal
      function in 3 of nine patients (33%) with non-malignant monoclonal gammopathy.
      Non-malignant monoclonal gammopathy could go unnoticed. Appearance of
      abnormalities in renal routine tests deserves more in-depth diagnostic
      procedures, including renal biopsy. Evolution to end stage renal disease could
      probably be avoided or reduced in severity with early detection and treatment of
      this entity.

PMID- 18816212
TI  - [Changes in vascular access in a dialysis unit in recent years: planning
      problems, change in preferences, or demographic change?].
AB  - BACKGROUND: Evidence on the reasons for the general and discouraging
      overutilization of catheters in DOPPS countries is lacking. METHODS: We analysed
      the changes in distribution of the different types of vascular access in all 398
      patients ongoing hemodialysis at our unit, from January 2000 until December 2005,
      as well as patients' characteristics. Secondly, risk factors associated with the
      use of permanent catheters were evaluated in all 95 patients who used that kind
      of vascular access from January 1997 until April 2006. RESULTS: The percentage of
      fistulas in prevalent patients diminished from year 2000 until year 2005 (from
      95% to 77.9%); concurrently there was an increase in the use of permanent
      catheters (from 4.2% to 21.5%). The percentage of incident patients having a
      usable fistula or graft at the beginning of hemodialysis diminished progressively
      (83.4% in 2000; 69.3% in 2005), and there was a significant increase in the
      percentage of incident patients using a permanent catheter (from 0 to 23%).
      Coincidentally, there was a change in patients characteristics: increasing age
      (71.3 vs. 60.5 years); greater diabetes percentage (7.1% vs. 18.5%) and less time
      on dialysis (93.2 vs 37 months; p < 0.03). Causes of permanent catheter insertion
      varied, exhaustion of all other arteriovenous options being the most frequent in
      the first period of the study and the presence of an unsuitable vascular anatomy
      in the second. CONCLUSIONS: Despite our policy favoring arteriovenous
      angioaccess, our results with regards to vascular access worsened in both
      prevalent and incident patients, coinciding with a change in patients'
      characteristics. We believe that reversing this trend may become more complicated
      as the population on dialysis grows older and becomes more prone to diabetes.

PMID- 18816213
TI  - [Light chain deposition disease. Experience in our environment].
AB  - The Light chain deposition disease (LCDD) is a strange entity characterised by
      the deposition of only one type of light chain in the renal tubular basement
      membranes. It can be associated to a plasma cell dyscrasia, however, it can occur
      in the absence of any detectable hematological disorder and it is called
      idiopathic LCDD. The clinical manifestation is renal insufficiency and nephrotic
      proteinuria, it does not have a clearly fixed treatment and has a severe
      prognosis. The aim of this work is to analyse the characteristics of the LCDD
      cases diagnosed within our environment. Six cases were identified, all of them
      between 1999 and 2005, from a total amount of 640 renal biopsies performed during
      this period, 4 women and 2 men, average age of 57. Multiple myeloma in 3 patients
      were detected (50%). The acute renal failure or rapidly progressive renal
      insufficiency was the most frequent clinical presentation (66%) together with
      nephrotic proteinuria (66%). All the biopsies showed tubular basement membranes
      thickening and kappa chains with a linear distribution within the same. The most
      frequent glomerular pathological finding was the nodular sclerosing
      glomerulopathy (83%). In one of the cases the affectation was exclusively tubular
      interstitial with tubular casts. 3 patients were treated, 2 with multiple
      myeloma. 5 patients needed dialysis: 3 with idiopathic LCDD within an average
      time of 7 days from the diagnosis to its reception and 2 with myeloma, who
      started needing dialysis in an average of 46 days. 4 patients died, 2 of them
      with myeloma. The monitoring time until the death was 13 weeks for the patients
      with myeloma and 110 weeks for the rest. CONCLUSION: The LCDD seems to be more
      frequent than what has been published and it is associated to the myeloma in half
      of the cases. It appears together with severe renal insufficiency and the
      patient's and renal prognosis is poor.

PMID- 18816214
TI  - [Tunneled catheters. Complications during insertion].
AB  - INTRODUCTION: The creation of vascular accesses for hemodialysis in patients
      affected with terminal kidney failure affections, is presented periodically as a
      problem. Because of it, the availability of alternatives to the arteriovein
      fistula is something necessary; different types of tunnelled dialysis catheters
      are being developed, among which the Tesio catheter is the most well known and
      most widely utilized. Often it is implanted by vascular surgeons or radiologists;
      this creates dependence for the nephrology services that can delay obtaining the
      new vascular access and initiating or reinitiating the treatment. MATERIAL AND
      METHODS: A descriptive study with the objective of analyzing the immediate
      complications during the insertion of tunnelled central catheters for
      hemodialysis and to evaluate the possibility of its attainment was carried out by
      nephrologists and personnel specialized in dialysis. Between January of 2003 and
      December of 2005, 175 Tesio tunnelled central catheters were implanted in our
      hemodialysis unit. Age and sex of the patient was registered, time in dialysis,
      diagnosis of hypertension, diabetes mellitus or prior heart disease, previous
      anticoagulant or platelet antiaggregate treatment, difficulty perceived by the
      nephrologist for the development of the technique, bleeding, systolic and
      diastolic arterial pressure, cardiac frequency, oxygen saturation and changes in
      the monitoring of electrocardiogram, at the beginning of the intervention, during
      the channelling of the vein, insertion of the dilatators and catheter, and at the
      end of it. RESULTS: The patients were 88 men and 82 women, with an average of age
      of 64. 21% of the patients habitually followed a treatment with platelet
      antiaggregate or anticoagulant, which had been withdrawn in the prior days. The
      ultrasound size of the vein was greater than one cm in 79% of the cases. Of 175
      insertions only three patients (2%) presented signs of hemodynamic instability,
      two of them due to a descent of arterial tension and one by oxygen saturation
      descent; none of them required assisted backup, neither hemorrhage nor other
      complications appeared. CONCLUSIONS: The implant of tunnelled catheters, under
      local anesthesia, presents minimal complications and incidents during its
      insertion. It can be carried out by a nephrologist and specialized personnel, in
      hospitals with backup units that can undertake any possible complications.

PMID- 18816215
TI  - [Hereditary disorders of magnesium reveal new proteins implicated in its renal
      transport].

PMID- 18816216
TI  - [Lupus nephritis and antiphospholipid syndrome].

PMID- 18816217
TI  - [Acute renal failure after intake of mushrooms].
AB  - The picking and consumption of wild mushrooms is a frequent practice in our
      region and may lead to accidental poisoning when confused with edible mushrooms.
      We describe the case of a 9-year-old boy who, following the ingestion of a
      poisonous mushroom, presented with uncontrollable vomiting and subsequent
      hepatic, haematological and renal failure some hours later. The patient required
      haemodialysis. The clinical course, laboratory findings and renal histology,
      which showed tubular necrosis with basal membrane preserved and lymphocytic
      interstitial infiltrate, confirmed the diagnosis of a severe mixed syndrome. The
      patient evolved favourably after the poisoning, recovering renal and liver
      function. In any case of acute renal failure of unknown cause in children, it
      would be necessary to rule out ingestion of mushrooms, since the patient could
      benefit from early treatment with haemoperfusion and thus prevent the
      deterioration of the renal function and other organs. In our patient,
      haemoperfusion was not carried out due to the lengthy period of latency since the
      ingestion of the toxic substance until diagnosis.

PMID- 18816218
TI  - [Comments on the comparison and agreement of equations to estimate glomerular
      filtration rate in diagnosis of occult chronic kidney disease].

PMID- 18816219
TI  - [Kidney transplant from a living donor provides the same results as kidney
      transplant from a cadaveric donor].

PMID- 18816220
TI  - [Renal function recovery on hemodialysis].

PMID- 18816221
TI  - [Rhabdomyolysis after correction of severe hyponatremia due to an attack of acute
      intermittent porphyria].

PMID- 18816222
TI  - [Recovery of total inmunoglobulin and immunoglobulin subclasses in nephrotic
      syndrome: deflazacort vs methylprednisone].

PMID- 18816223
TI  - [Biliptysis as the initial symptom of a rare complication of autosomal dominant
      polycystic kidney disease].

PMID- 18816224
TI  - [Metastatic pulmonary calcinosis].

PMID- 18816225
TI  - [Cryptococcosis in a patient with IgA nephropathy treated with corticosteroids].

PMID- 18816226
TI  - [Intracranial hypertension as presentation of neurobrucellosis in a patient on
      hemodialysis].

PMID- 18816227
TI  - [Genetic and environment: pathogenetic factors of vasculitis?].

PMID- 18816228
TI  - [Hypokalemia, distal renal tubular acidosis, and Hashimoto's thyroiditis].

PMID- 18816229
TI  - [Hyponatremia secondary to cerebral salt-wasting syndrome associated to bacterial
      meningitis].

PMID- 18816230
TI  - [Disseminated histoplasmosis in a kidney transplant patient].

PMID- 18816231
TI  - [Autoimmune thyroiditis, subclinical hypothyroidism, and nephrotic syndrome
      caused by membranous nephropathy].

PMID- 18816234
TI  - Living-related liver transplantation in an adult and a child.

PMID- 18816235
TI  - Risk factors for biliary complications after living-donor liver transplant: a
      single-center experience.
AB  - OBJECTIVES: Biliary complications remain a major concern in living-donor liver
      transplant. They can lead to patient and graft loss. In this study, we
      retrospectively analyzed patients' records to identify factors that increase the
      frequency of biliary complications in living-donor liver transplant with an aim
      toward decreasing this frequency. MATERIALS AND METHODS: We performed 53 living
      donor liver transplants between November 2002 and September 2007. Five cases were
      excluded because of graft or patient loss within 2 weeks resulting in 48 cases
      available for analysis. The effect of the following variables on the frequency of
      biliary complications was analyzed: recipient age, liver lobe used, number of
      graft bile ducts, number of biliary anastomoses, type of biliary anastomosis, and
      bile duct diameter 4 mm or smaller. RESULTS: Biliary complications were seen in
      14 cases (29.1%). These included 9 biliary strictures, 3 bile leaks, and 2 bile
      leaks eventually healing as biliary strictures. The presence of more than 1 graft
      bile duct increased the frequency of biliary complications (P = .03). The other
      variables did not have a statistically significant effect on the frequency of
      biliary complications. CONCLUSIONS: The rate of complications in our experience
      is comparable to that already published. The presence of more than 1 bile duct in
      the graft is a risk factor for biliary complications in living-donor liver
      transplant. A review of the data suggests additional risk factors.

PMID- 18816236
TI  - Interventional radiology in liver transplant.
AB  - An increased number of transplant centers now actively perform deceased-donor as
      well as living-related liver transplants. Although postoperative vascular and
      nonvascular complications after liver transplant have been well documented, early
      diagnosis and intervention are important to increase graft and recipient
      survival. With improvements in interventional radiologic techniques and a
      multidisciplinary approach to liver transplant, management of complications by
      percutaneous and endovascular techniques is possible with less morbidity and
      mortality. This article outlines the recent developments in, and applications of,
      interventional radiologic techniques in liver transplant patients.

PMID- 18816237
TI  - A retrospective study of conversion from tacrolimus-based to sirolimus-based
      immunosuppression in orthotopic liver transplant recipients.
AB  - OBJECTIVES: Calcineurin inhibitors are used widely in liver transplant
      recipients. Sirolimus is a new, potent immunosuppressant considered to be
      nonnephrotoxic. There is limited experience with the use of sirolimus in liver
      transplant recipients. This study aimed to investigate the clinical experience of
      conversion from tacrolimus-based to sirolimus-based immunosuppression in liver
      transplant recipients. Patients switched to cyclosporine-based immunosuppression
      during the same period were enrolled as controls. MATERIALS AND METHODS: This
      retrospective study examined liver transplant recipients who had been switched
      from tacrolimus-based to sirolimus-based or cyclosporine-based immunosuppressive
      therapy between January 2004 and January 2007 in the First Affiliated Hospital of
      Sun Yat-sen University. Patients were divided into 3 groups: those switched to
      sirolimus-based immunosuppression owing to acute rejection (group SIR-AR; n=11);
      those switched to sirolimus-based immunosuppression owing to renal insufficiency
      (group SIR-RI; n=18), and those switched to cyclosporine-based immunosuppression
      owing to acute rejection (group CsA-AR; n=15). RESULTS: In patients switched
      owing to acute rejection, the rate of successful conversion was 54.5% in group
      SIR-AR (6/11) compared with 60% in group CsA-AR (9/15); this difference was not
      statistically significant (P > .05). After conversion, renal function in patients
      in group SIR-AR remained normal. Conversely, renal function in patients in group
      CsA-AR became abnormal 3 months after conversion. In patients who were switched
      owing to renal insufficiency in group SIR-RI, renal function improved
      significantly after conversion (P < .05). In the sirolimus groups, some sirolimus
      associated adverse effects occurred but were limited and well controlled.
      CONCLUSIONS: Sirolimus can be used safely in liver transplant recipients. In the
      early stages after liver transplant, sirolimus combination therapy is recommended
      to prevent acute rejection. For patients with tacrolimus-related adverse effects,
      a sirolimus-based immunosuppression regimen is a rescue therapy.

PMID- 18816238
TI  - Influence of long chain polyunsaturated fatty acids and ornithine concentrations
      on complications after renal transplant.
AB  - OBJECTIVES: The present study, registered at clinicaltrials.gov with the unique
      registration number NCT00560014, sought to evaluate the relations between fatty
      acid concentrations in red blood cells or plasma and amino acid concentrations in
      plasma on rejection, calcineurin inhibitor toxicity, and new-onset diabetes
      mellitus. MATERIALS AND METHODS: Lipid profiles on plasma or red blood cell
      samples were performed preoperatively and postoperatively in 54 patients. Plasma
      amino acid profiles were obtained in 49 of these patients. RESULTS: High
      concentrations of total omega-3 fatty acids, eicosapentaenoic and docosahexaenoic
      acids in red blood cells, and ornithine in plasma, all were associated with a
      significantly lower incidence of rejection, whereas high total omega-6 fatty
      acids were associated with a high rejection rate. Calcineurin inhibitor toxicity
      was associated with low levels of docosahexaenoic acid, ornithine, and the omega
      3 index, and high total omega-6 and omega-3/omega-6 ratios. Inhibition of new
      onset diabetes mellitus was seen only with high levels of ornithine. Peak
      concentrations of fatty acids in red blood cells were not obtained until after 30
      days. High levels of arginine were not associated with reduced complications.
      CONCLUSIONS: The levels of selected nutrients in plasma and red blood cell
      membranes appear to have a profound effect on complications after renal
      transplant. These preliminary results need confirmation in prospective randomized
      clinical trials.

PMID- 18816239
TI  - Orthostatic hypotension in kidney pancreas transplant patients and its relation
      to preexisting autonomic neuropathy.
AB  - OBJECTIVES: Orthostatic hypotension is a known complication of pancreas
      transplant. This retrospective study of 25 kidney-pancreas transplant patients at
      our center was done to determine the incidence and course of postoperative
      orthostatic hypotension. MATERIALS AND METHODS: A chart review was done for all
      patients who received a kidney-pancreas transplant between January 1997 and
      December 2005. Patients with orthostatic hypotension after surgery were selected
      and compared with patients without orthostatic hypotension for preexisting
      autonomic and peripheral neuropathy status. The kidney-pancreas transplant group
      was then compared with a group of diabetic kidney-only transplant recipients to
      assess the contribution of the renal transplant in this process. RESULTS: Seven
      kidney-pancreas transplant patients (28%) developed orthostatic hypotension after
      the transplant. It occurred with much higher frequency in kidney-pancreas
      transplant patients than it did in kidney transplant patients (P = .002). The
      onset of orthostatic hypotension was between 8 and 20 days after transplant. Six
      patients required midodrine for symptomatic relief. Orthostasis resolved
      completely within 3 weeks to 9 months in all but 1 patient. There was no
      correlation between postoperative orthostasis and preoperative history of
      orthostatic hypotension, gastroparesis, or peripheral neuropathy. Orthostasis was
      related to posttransplant polyuria in only 1 patient. In the remaining patients,
      orthostasis seemed to be related to the presence of the pancreas transplant. The
      exact pathogenesis of orthostasis is unclear but may be related to
      hyperinsulinemia after transplant or neuropeptides involved in the regenerative
      process. CONCLUSIONS: Orthostatic hypotension is common after kidney-pancreas
      transplant. It is unrelated to preexisting autonomic neuropathy or posttransplant
      polyuria in most patients. This complication requires further study.

PMID- 18816240
TI  - Cytomegalovirus disease in renal transplant recipients: an Iranian experience.
AB  - BACKGROUND: Cytomegalovirus is considered the most important infectious cause of
      mortality and morbidity in organ transplant recipients. In the current study, we
      evaluate the potential impact of cytomegalovirus infection and cytomegalovirus
      disease on the outcomes of renal allograft recipients under different conditions.
      MATERIALS AND METHODS: We retrospectively analyzed the data from 48 renal
      transplant recipients who had undergone a transplant at the Baqiyatallah Hospital
      in Tehran, Iran, between 1984 and 2007. We included all patients with valid
      laboratory test results for cytomegalovirus infection. Values for P less than .05
      were considered statistically significant. RESULTS: Overall, 48 patients (2.1%)
      were documented as developing cytomegalovirus disease. From these, 1 patient (2%)
      died, and 3 (6%) lost their allograft function. Compared with mycophenolic-acid
      based triple immunosuppressive therapy, azathioprine was less likely to induce
      cytomegalovirus disease and also promised better survival (P < .0001 and P <
      .001). Being negative for the anti-cytomegalovirus IgG antibody and receiving an
      allograft from a positive donor also were associated with cytomegalovirus disease
      development and poorer patient survival (P = .03 and P < .0001). CONCLUSIONS:
      Cytomegalovirus infection induces unfavorable outcomes in renal allograft
      recipients, especially when the infection occurs early on in the posttransplant
      phase. We suggest close monitoring of cytomegalovirus-positive patients and the
      use of less-intensive immunosuppressive treatments. Future prospective studies
      seem necessary.

PMID- 18816241
TI  - Parvovirus B19 microepidemic in renal transplant recipients with thrombotic
      microangiopathy and allograft vasculitis.
AB  - Parvovirus B-19 (B-19) can lead to various clinical scenarios in renal transplant
      recipients. Here, we report a B-19 microepidemic that occurred between January
      and March 2007, involving renal transplant recipients from a single center in
      Tabriz, Iran. We observed 6 patients in whom there was a temporal association
      between active B-19 infection and thrombotic microangiopathy and intrarenal small
      and medium-sized vessel vasculitis. Patients typically presented with
      deteriorating renal allograft function and anemia, and laboratory findings
      revealed thrombotic microangiopathy. Ultimately, extensive endothelial injury and
      renal allograft vasculitis that mimicked a vascular rejection ensued. In
      conclusion, B-19-related thrombotic microangiopathy may precede allograft
      vasculitis in renal transplant recipients. A high index of suspicion is required
      for early diagnosis and treatment of B-19 infection. To the best of our
      knowledge, this series represents the first report of B-19-related renal
      allograft vasculitis in the English literature.

PMID- 18816242
TI  - Modification of Diet in Renal Disease equation underestimates glomerular
      filtration rate in Egyptian kidney donors.
AB  - OBJECTIVES: Inulin clearance and radioisotope studies are the most accurate means
      of measuring glomerular filtration rates (GFRs). The Kidney Disease Outcomes
      Quality Initiative guidelines recommend estimating GFRs with the Modification of
      Diet in Renal Disease (MDRD) or the Cockcroft- Gault equation. We examined the
      accuracy of the MDRD equation and creatinine clearance based on 24-hour urine
      collection to predict GFRs in a group of healthy donors. MATERIALS AND METHODS:
      We examined the medical records of 100 kidney donors who had undergone 99mTc
      diethylenetriamine-pentaacetic acid (DTPA) renal clearance and creatinine
      clearance measurements at the transplant outpatient clinic of Cairo University
      Hospital in Cairo, Egypt, between June 2002 and July 2006. GFR was predicted with
      the abbreviated MDRD formula. We examined significant differences, potential
      correlations, and agreements between GFR as predicted and as measured. RESULTS:
      The mean eGFRMDRD was 8.16% lower than the 99mTc-DTPA GFR (116.11 -/+
      25.44mL/min/1.73m2 vs 126.32 -/+ 24.21 mL/min/1.73 m2; difference range, -84 to
      +61 mL/min/1.73 m2; P = .002). Creatinine clearance was 13.14% higher than the
      99mTc-DTPA GFR (142.90 -/+ 27.51 mL/min/1.73 m2; difference range, +65 to -60
      mL/min/1.73 m2; P < .001). A significant positive correlation was observed when
      creatinine clearance and 99mTc-DTPA-measured GFR were compared (R=0.451; P =
      .000). No significant correlation was noted between eGFRMDRD and 99mTc-DTPA
      measured GFRs (R=0.126; P = .211). A Bland-Altman analysis showed poor agreement
      between GFRMDRD and creatinine clearance on the one hand and measured GFR on the
      other. CONCLUSIONS: Neither the MDRD equation nor creatinine clearance is
      accurate in predicting GFRs in healthy donors.

PMID- 18816243
TI  - Comparison of antigenemia assay and semiquantitative polymerase chain reaction
      test for monitoring active cytomegalovirus infection in allogeneic hematopoietic
      cell transplant recipients.
AB  - OBJECTIVES: We sought to compare the antigenemia assay and in-house
      semiquantitative polymerase chain reaction to monitor human cytomegalovirus
      infection after transplant in hematopoietic cell transplant recipients. MATERIALS
      AND METHODS: A pp65 antigen test for polymorphonuclear leukocytes and a
      semiquantitative polymerase chain reaction for whole blood were performed for 201
      samples obtained from 26 hematopoietic cell transplant recipients over a 3-month
      surveillance period. RESULTS: Fourteen episodes of antigenemia positivity were
      detected in 7 patients in whom human cytomegalovirus DNA loads and pp65-positive
      cells ranged between < 102 to 2.96 x 104 copies/mL and 0-35/ 5 x 104
      polymorphonuclear leukocytes, respectively. A significant correlation was
      detected between human cytomegalovirus DNA load and the antigenemia test. A
      receiver operating characteristic analysis determined 5000 copies/mL of human
      cytomegalovirus as the threshold value for initiation of ganciclovir therapy.
      CONCLUSIONS: Based on a comparison of the pp65 antigenemia assay, quantification
      of human cytomegalovirus DNA in whole blood can be used to guide clinical
      management of hematopoietic cell transplant recipients. This approach may have
      important advantages including superior sensitivity and efficient monitoring of
      preemptive therapy, allowing inclusion of kinetic criteria in clinical
      guidelines. Furthermore, a high human cytomegalovirus load among patients with
      grade II-IV acute graft-versus-host disease may indicate a high risk of human
      cytomegalovirus disease among hematopoietic cell transplant patients. Human
      cytomegalovirus reactivation must be monitored using more-sensitive assays such
      as real-time polymerase chain reaction.

PMID- 18816244
TI  - Characteristics of recipients whose kidney allograft has functioned for more than
      20 years.
AB  - OBJECTIVES: To study the characteristics of, and predictors for, survival in
      renal transplant recipients with an allograft functioning for more than 20 years.
      MATERIALS AND METHODS: Of 144 renal transplants done between 1976 and 1985, 31
      allografts were still functioning for more than 20 years (range, 21- 28.5 years).
      The characteristics of the patients and determinants of the outcomes were
      obtained by reviewing the patients' medical records. RESULTS: Fourteen patients
      were treated with cyclosporine, while 17 patients had primary immunosuppression
      with azathioprine-based regimens. Episodes of acute rejection occurred in 17
      patients (58%), 7 of these experienced 2 or more episodes. At most-recent follow
      up, the mean serum creatinine level was 132 +/- 44 micromol/L . Four patients
      were assessed by graft biopsy 15 or more years after the transplant, revealing 2
      cases of mild glomerulosclerosis and 2 cases of moderate chronic allograft
      nephropathy. The most common complication was hypertension (54%). The independent
      determinants of long-term graft survival were donor age and source, hypertension
      both before and after renal transplant, and histopathological findings of chronic
      allograft nephropathy. CONCLUSIONS: Renal transplant offers a near-normal life to
      patients with end-stage renal disease soon after transplant and for upwards of 20
      years and more. We found no significant benefit to cyclosporine-based
      immunosuppression on long-term graft survival.

PMID- 18816245
TI  - Serial resistive index and pulsatility index for diagnosing renal complications
      in the early posttransplant phase: improving diagnostic efficacy by considering
      maximum values.
AB  - OBJECTIVES: To present new approaches to using duplex Doppler scanning to detect
      kidney complications in the early posttransplant period. MATERIALS AND METHODS:
      We assessed the resistive index and the pulsatility index in 127 renal transplant
      patients (73 men, mean age, 35.2 +/- 14 years) who underwent duplex Doppler
      scanning on the first, third, and fifth days after transplant. Biopsies were
      performed in patients suspected of having graft dysfunction owing to clinical and
      laboratory findings. To differentiate complicated from healthy grafts, a receiver
      operating characteristic curve analysis was done, and an area under the curve was
      calculated for each variable. RESULTS: In total, 47 grafts (37%) became
      complicated (40 rejections). The mean resistive index and mean pulsatility
      indexwere statistically significantly higher on the first, third, and fifth days
      after transplant in patients with complicated grafts than they were in patients
      with noncomplicated grafts (P < .0001). The mean resistive index and mean
      pulsatility index showed a significant rise from the first to the fifth day in
      patients with complicated grafts (P = .014). The area under the curve of the
      receiver operating characteristic curve for resistive index and pulsatility index
      on successive days was statistically significant (P < .0001). The resistive index
      and the pulsatility index area under the curve were statistically significantly
      lower on the first day than they were on subsequent days. Considering the maximum
      value of a serially measured resistive index and pulsatility index (which were
      determined by comparing 3 measurements on the fifth day and selecting the highest
      one) as a new variable showed a better area under the curve compared with that
      calculated on the third day (P = .05 for resistive index; P = .012 for
      pulsatility index). CONCLUSIONS: The resistive index and the pulsatility index
      are effective means of diagnosing posttransplant renal complications. Including a
      serial assessment and considering the maximum values could improve the diagnostic
      efficacy on the fifth day after transplant.

PMID- 18816246
TI  - End-stage vascular access: direct intra-atrial insertion of a dialysis catheter.
AB  - Central venous occlusions are a frequent problem in hemodialysis patients. We
      describe the case of a patient with end-stage vascular access in whom we
      successfully inserted a direct intra-atrial dialysis line during coronary artery
      bypass grafting. This technique could be a significant contribution to patients
      in whom alternative vascular access options are exhausted.

PMID- 18816247
TI  - IGF-I/IGFBP-3 ratio: a mechanistic insight into the metabolic syndrome.
AB  - Recent reports suggest that IGF (insulin-like growth factor)-I and IGFBP-3 (IGF
      binding protein-3) have independent and opposing mechanistic effects on insulin.
      The aim of the present study was to assess the relationship between the IGF
      I/IGFBP-3 ratio and the metabolic syndrome. We examined 3281 subjects (1463 men
      and 1818 women, aged 20-49 years), otherwise healthy adults, who participated in
      NHANES III (Third National Health and Nutrition Examination Survey), which has
      released measurements of IGF-I and IGFBP-3. Insulin resistance was estimated
      using the computer HOMA2 (homoeostatic model assessment 2) model. The updated ATP
      III (Adult Treatment Panel III) definition of the metabolic syndrome was used. We
      applied adjusted logistic and linear regression models. After adjusting for age
      and race, men and women in the lowest quartile of the IGF-I/IGFBP-3 ratio were 3
      fold more likely to meet the ATP-III definition of the metabolic syndrome and
      twice as likely to be insulin-resistant. Mean values of the IGF-I/IGFBP-3 ratio
      decreased significantly as the number of metabolic syndrome components increased
      (P<0.0001, as determined by ANOVA). The area under the ROC (receiver operating
      characteristic) curve for detecting insulin resistance using the IGF-I/IGFBP-3
      ratio was 0.760, significantly improving upon either protein alone (P=0.01). In
      conclusion, the IGF-I/IGFBP-3 ratio is significantly associated with the
      metabolic syndrome. Calculating the ratio of these two proteins may provide
      insight into the metabolic syndrome clustering phenomenon.

PMID- 18816248
TI  - Vascular endothelial growth factor acts through novel, pregnancy-enhanced
      receptor signalling pathways to stimulate endothelial nitric oxide synthase
      activity in uterine artery endothelial cells.
AB  - During pregnancy, VEGF (vascular endothelial growth factor) regulates in part
      endothelial angiogenesis and vasodilation. In the present study we examine the
      relative roles of VEGFRs (VEGF receptors) and associated signalling pathways
      mediating the effects of VEGF(165) on eNOS (endothelial nitric oxide synthase)
      activation. Despite equal expression levels of VEGFR-1 and VEGFR-2 in UAECs
      (uterine artery endothelial cells) from NP (non-pregnant) and P (pregnant) sheep,
      VEGF(165) activates eNOS at a greater level in P- compared with NP-UAEC,
      independently of Akt activation. The selective VEGFR-1 agonist PlGF (placental
      growth factor)-1 elicits only a modest activation of eNOS in P-UAECs compared
      with VEGF(165), whereas the VEGFR-2 kinase inhibitor blocks VEGF(165)-stimulated
      eNOS activation, suggesting VEGF(165) predominantly activates eNOS via VEGFR-2.
      Although VEGF(165) also activates ERK (extracellular-signal-regulated kinase)
      1/2, this is not necessary for eNOS activation since U0126 blocks ERK-1/2
      phosphorylation, but not eNOS activation, and the VEGFR-2 kinase inhibitor
      inhibits eNOS activation, but not ERK-1/2 phosphorylation. Furthermore, the
      inability of PlGF to activate ERK-1/2 and the ability of the VEGFR-2 selective
      agonist VEGF-E to activate ERK-1/2 and eNOS suggests again that both eNOS and ERK
      1/2 activation occur predominantly via VEGFR-2. The lack of VEGF(165)-stimulated
      Akt phosphorylation is consistent with a lack of robust phosphorylation of
      Ser(1179)-eNOS. Although VEGF(165)-stimulated eNOS phosphorylation is observed at
      Ser(617) and Ser(635), pregnancy does not significantly alter this response. Our
      finding that VEGF(165) activation of eNOS is completely inhibited by wortmannin
      but not LY294002 implies a downstream kinase, possibly a wortmannin-selective
      PI3K (phosphoinositide 3-kinase), is acting between the VEGFR-2 and eNOS
      independently of Akt.

PMID- 18816250
TI  - The effects of different concentrations of acetylsalicylic acid on proliferation
      and viability of lymphocytes in cell culture.
AB  - Numerous studies conducted on acetylsalicylic acid (ASA, aspirin) confirmed that
      ASA inhibits proliferation and induces apoptosis in various types of human cells.
      Therefore, it was of interest to examine possible effects of different
      concentrations of ASA on viability and proliferation of lymphocytes in the cell
      culture. After separation from blood, lymphocytes were suspended in RPMI 1640
      medium and cultured at 37 degrees C. Solution of ASA was added to cultures after
      24 h, in final concentrations of 1, 3 and 5 mmol/l. After 48 h, proliferative
      response was evaluated by WST-1 assay. Significant difference in viability
      between controls and cell cultures treated with ASA in three different
      concentrations was observed (p<0.01). Percents of viable cells in cultures after
      application of 1, 3 and 5 mmol/l ASA were 9.9%, 2.5% and 16.9% (compared to
      controls), respectively. To determine whether this cytotoxic effect was result of
      induction of apoptosis, DNA from cell cultures was isolated and subjected to
      agarose gel electrophoresis. Fragmentation of DNA was not detected, excluding
      apoptosis as possible cause of cytotoxic effects. Addition of ASA caused change
      of initial extracellular pH value for each treated culture. After addition of 1
      mmol/l ASA, pH of culture was 7.19, after 3 mmol/L, 6.99 and after addition of 5
      mmol/l solution, pH was 6.75. Decreased lymphocyte viability could be attributed
      to either the effects of the added substance or possible further acidification of
      cell cultures during three days of incubation.

PMID- 18816251
TI  - Effects of fixed combination of lisinopril plus hydrochlorothiazide on regression
      of left ventricular hypertrophy in patients with essential hypertension: an
      opened, multi-centre, prospective clinical trial.
AB  - The aim of this trial was to examine the effects of antihypertensive fixed
      combination of lisinopril plus hydrochlorothiazide (Lopril H, Bosnalijek dd,
      Bosnia and Herzegovina) on regression of left ventricular hypertrophy in patients
      with essential arterial hypertension. We included 297 patients in our trial, aged
      54.65+/-9.6 years, with treated or untreated hypertension and with high risk of
      cardiac events, in an opened trial of therapy based on lisinopril plus
      hydrochlorothiazide. Patients from five European countries were followed up for a
      period of 12 weeks. Duration of treatment was 12 weeks. We adjusted daily doses
      of lisinopril plus hydrochlorothiazide after every clinical examination and
      recorded adverse effects of drugs. In the beginning and after 12 weeks of
      treatment, 277 patients (93.2%) underwent 2-dimensional echocardiography and
      there were 186 patients evaluated for efficacy of treatment on left ventricular
      hypertrophy (LVH). We recorded a regression of index mass LVH (168.56 vs 161.51
      g/m2, P<0.0001), and regression was something more in women vs men. We recorded
      average reduction of left ventricular mass index for patients with LVH (N=186) by
      7.05 g/m2 (4.18%) in all patients, by 6.73 g/m2 (3.93%) in men and 7.27 g/m2
      (4,37%) in women. The proportion of patients who attained a regression of left
      ventricular mass tended to be greater in men (54.55% vs 53.21%). This research
      has proved regression of LVH in more than 53% patients after using fixed
      combination of lisinopril plus hydrochlorothiazide.

PMID- 18816252
TI  - In vitro examination of degenerative evolution of adrenergic nerve endings in
      pulmonary inflammatory [corrected] processes in newborns.
AB  - Morphological aspect of tracheal preparations and pulmonary tissue was studied in
      vitro. The material was obtained from autopsy of newborns that died from
      different causes. Examinations were made in different gestational periods
      (immature 23-29 weeks; premature 30-37 weeks; mature >38 weeks). Material for
      examination was obtained up to 6 hours after death. Pulmonary and tracheal tissue
      was incubated for fixation in buffered formalin (10%). Special histochemical and
      histoenzymatic methods were used for coloring of pulmonary and tracheal tissue
      and the activity of ATP-ase and dopaoxidase was monitored. Cut out models were
      made in series of 7 micro, 10 micro and 20 micro. In peripheral axons of
      tracheobronchial pathways, degenerative alterations of adrenergic nerve endings
      in lung inflammatory processes were documented. These morphologic neuronal
      changes were described: Walerians degeneration, neuro-axonal degeneration and
      segment demyelinisation. These changes are well seen with argentafine coloring
      (Sevier-Munger modification for nerve endings) and with dopaoxidase reaction. In
      mature newborns that died from respiratory distress syndrome, we found different
      forms of metabolic and toxic degenerative damage in peripheral axons, such as:
      segment demyelinisation, neurotubular fragmentation, Schwann cell proliferation,
      fragmentation and bulging out of axonal neurotubules and neurofilaments. In
      tracheo-bronchial tissue, chromafine granules are homogeneously distributed on
      Lamina propria layer and through glandular structures. This gives as a
      contradiction, according to some authors, that adrenergic nerve fibers for muscle
      tissue are absent and that adrenaline and noradrenaline diffuse in muscle tissue
      from interstice.

PMID- 18816253
TI  - Third coronary artery.
AB  - The human hart is in most cases vascularized by two coronary arteries, the right
      and the left one. Supernumerary or added coronary arteries are also present
      sometimes. The aim of this paper is to ascertain presence of supernumerary
      coronary arteries that arise directly from aorta, their frequency, flow, way of
      branching, and possibly their anastomoses with other coronary arteries. Out of 25
      hearts, examined by dissection, 8 of them (32%) had conal artery. According to
      our opinion, the most suitable term for this artery, in order to differ it
      clearly from the conal branch of the right coronary artery, is third coronary
      artery. One heart (4%) had four coronary arteries. Both supernumerary coronary
      arteries arose from the right aortic sinus. The third coronary artery represents
      a significant way of collateral coronary circulation, as it frequently
      anastomoses with anterior interventricular branch.

PMID- 18816254
TI  - Treatment of IgA nephropathy of adults presented by nephrotic syndrome.
AB  - The aim of this retrospective study was to evaluate the results of the
      immunosuppressive regiment in managing of IgA nephropathy associated with primary
      nephrotic syndrome at the Nephrology Clinic, University of Sarajevo Clinics
      Centre in period of 1997-2007. We studied 19 patients (4 women and 15 men) with
      idiopathic nephrotic syndrome, where pathomorphologic changes of IgA nephropathy
      were proved by kidney biopsy. The levels of diuresis, proteinuria, albuminemia,
      lipidemia and kidney function, as measure of efficiency of used therapy, were
      monitored. The IgA nephropathy present with the nephrotic syndrome was shown in
      15.8% (19) patients underwent renal biopsy due to primary nephrotic syndrome in
      the period of observation. The average age of patients with IgA nephropathy was
      34.9+/-14.1 years. Eight patients from this group were treated with
      corticosteroid therapy (1-1.5 mg/kg of body weight for 4 weeks, followed by 0.5
      mg/ kg of body weight until therapeutic response was achieved, and finally
      gradual exclusion of therapy after eight weeks in responsive patients), 6
      patients with corticosteroids and bolus cyclophosphamide (10-15 mg/kg BW), and in
      5/19 patients cyclosporine therapy was used (3 mg/kg BW). Complete remission of
      nephrotic syndrome was achieved in 42.1% of the patients. In conclusion, in
      adults patients with primary nephrotic syndrome associated with IgA nephropathy,
      used immunosuppressive therapy resulted in a high percentage of achieved
      remissions.

PMID- 18816255
TI  - Cardiac sarcoidosis mimicking Takotsubo syndrome.
AB  - An unusual case of cardiac sarcoidosis is described. A woman with biopsy proven
      lung sarcoidosis was presented on admission in hospital as ventricular
      tachycardia and non Q myocardial infarction. Ultrasound of the heart and
      coronarography examination presented Takotsubo syndrome, "ballooning heart", and
      normal blood vessels. Cardiac sarcoidosis and Takotsubo syndrome are diseases
      where definitive etiological factor was not found. This case report suggests the
      existence of their similar pathogenesis. As far as we know, this is the first
      described connection between Takotsubo syndrome and cardiac sarcoidosis.

PMID- 18816256
TI  - Genetic characterisation of rabies virus isolates in Bosnia and Herzegovina.
AB  - Serotyping of five rabies virus isolates with monoclonal anti-nucleoprotein
      antibodies for classical rabies virus and rabies-related viruses and phylogenetic
      relationships among sequences indicate that viruses circulating in population of
      animals in Bosnia and Herzegovina belong to the sero-genotype 1 of classical
      rabies virus. Phylogenetic relationships among sequences of our viruses have
      shown the presence of two phylogenetic lines, one which is present in the
      northwestern part and other which is present in the northeastern part of the
      country. Our viruses are closely related to Westeuropean isolates of rabies
      virus.

PMID- 18816257
TI  - Optimization of diagnostic ELISA-based tests for the detection of auto-antibodies
      against tumor antigens in human serum.
AB  - Colorectal cancer is one of the most common cancer types worldwide and it
      continues to be a serious public health problem. Early detection and diagnosis
      are of great importance in cancer management. At present, diagnostic blood tests
      are based on the detection of tumor-associated markers such as carcino-embryonic
      antigen (CEA), the cancer antigen CA19-9 for gastrointestinal cancer, CA15-3 for
      breast cancer or CA125 for ovarian cancer. The lack of sensitivity and
      specificity of these markers prevents their general use in cancer screening of an
      average risk population. Therefore, new cancer biomarkers or better screening
      methods are necessary to improve the diagnostics of the disease. This study was
      directed to the optimization of a diagnostic, enzyme linked immunosorbent assay
      (ELISA) based test to identify and validate new serum markers, such as
      extracellular Protein Kinase A (ecPKA) and Nicotinamide N-Methyltransferase
      (NNMT). In this type of assay, the cancer antigens are quantified indirectly - by
      detecting the presence of auto-antibodies against tumor proteins in human serum.
      The result of the optimization and validation process was in the case of ecPKA a
      reproducible and stable assay. In case of NNMT the assay was probably not
      sensitive enough.

PMID- 18816258
TI  - Doppler sonography characteristics of vertebrobasilar circulation in patients
      with Parkinson's disease.
AB  - The objective of the study was to analyze the doppler sonography findings of
      vertebrobasilar circulation (VB) in patients with Parkinson's disease. 40
      patients were analyzed (25 men's and 15 women) with Parkinson's disease, average
      age was 61.9 years (SD=11.43), treated at the Clinic for Neurology in Tuzla.
      Device for doppler sonography was Multidop x 4. Doppler sonography findings of VB
      circulation were analyzed in order to computerized tomography (CT) findings of
      the brain (with or without ischemic lacunar lesions) and in order to presence of
      postural disturbances as one of dominant Parkinson's disease symptoms during
      actual hospitalization. Our results suggest that vertebrobasilar insufficiency is
      more frequent in patients with Parkinson's disease (no matter of type) and
      postural disturbances as a dominant symptom comparing to group of Parkinson's
      disease patients without postural disturbances. These results implicate the
      importance of doppler sonography findings of vertebrobasilar circulation in
      patients with Parkinson's disease and possibility of considering role of
      vertebrobasilar insufficiency in development of postural disturbances.

PMID- 18816259
TI  - Stability of anthocyanins from commercial black currant juice under simulated
      gastrointestinal digestion.
AB  - Anthocyanins are effective antioxidants but they have also been proposed to have
      other biological activities independent of their antioxidant capacities that
      produce health benefits. Examples range from inhibition of cancer cell growth in
      vitro, induction of insulin production in isolated pancreatic cells, reduction of
      starch digestion through inhibition of a-glucosidase activity, suppression of
      inflammatory responses as well as protection against age-related declines in
      cognitive behavior and neuronal dysfunction in the central nervous system.
      However, to achieve any biological effect in a specific tissue or organ,
      anthocyanins must be bioavailable; i.e. effectively absorbed from the
      gastrointestinal tract (GIT) into the circulation and delivered to the
      appropriate location within the body. In this study, we assess the stability of
      anthocyanins from commercial Black currant (Ribes nigrum L.) juice using an in
      vitro digestion procedure that mimics the physiochemical and biochemical
      conditions encountered in the gastrointestinal tract (GIT). The main objective of
      this work was the evaluation of stability of anthocyanins during in vitro
      digestion in gastric and intestinal fluid regarding whether appropriate enzyme
      (pepsin or pancreatin) was added or not. Anthocyanins present in commercial black
      currant juice remain stable during in vitro digestion in gastric fluid regardless
      whether pepsin was added into the medium or not. Also, they remain stable during
      in vitro digestion in simulated intestinal fluid without pancreatin. The
      stability studies of anthocyanins in the intestinal fluid containing pancreatin
      indicated reduced stability, which also mainly contribute to slight reduction of
      total anthocyanins content (-1.83%) in commercial black currant juice.

PMID- 18816260
TI  - Epidemiologic genotyping of methicillin-resistant Staphylococcus aureus (MRSA) by
      pulsed-field gel electrophoresis (PFGE).
AB  - Staphylococcus aureus has long been recognized as one of the leading cause of
      hospital infections all over the world. Increased frequency of methicillin
      resistant Staphylococcus aureus (MRSA) in hospitalized patients and possibility
      of vancomycin resistance requires rapid and reliable characterization of isolates
      and control of MRSA spread in hospitals. Typing of isolates helps to understand
      pathogenesis and route of the hospital pathogen spread. In this study, in the
      analysis of an outbreak of MRSA infections in one surgical ward, we used pulsed
      field gel electrophoresis (PFGE) as a method of typing. PFGE revealed one
      epidemic strain type A in 13 out of 16 patients, and another two types (type B in
      two patients and type C in one patient). Discussing the typing results in the
      ward has changed the admission policy of patients with infected vascular ulcers
      who were then cured as outpatients, and admitted for surgery after that. This
      policy resulted with the stopping of the outbreak; during next 2.5 year there was
      no further MRSA outbreak in the ward. PFGE also showed subtypes which enabled the
      insight into dynamics of MRSA strain changes during the outbreak. PFGE could be
      recommended as a screening method in the MRSA outbreak analysis. Because of it's
      high discriminatory power still remains the gold standard for MRSA typing.

PMID- 18816261
TI  - Management [corrected] of conversions to cardiopulmonary bypass in beating heart
      coronary surgery.
AB  - This study investigated outcomes in patients undergoing coronary artery bypass
      grafting (CABG) without cardiopulmonary bypass (CPB), who needed conversion to
      CPB. Between September, 1998 and September, 2003, 1000 CABG procedures were
      performed in a Cardiovascular Clinic, University Clinical Centre Tuzla.
      Multivessel CABG were selected arbitrarily for CABG without CPB (OPCAB) or CABG
      with CPB (ONCAB). Patients who required conversion due to technical difficulty
      with grafting were performed with ONCAB including cardioplegic arrest. Patients
      with severe hemodynamic instability and cardiac arrest were performed as ONCAB
      without crossclamping, while patients converted for mild to moderate hemodynamic
      instability were given cardioplegic arrest or not, depending on surgeon
      preference. 493 operations were scheduled and performed as ONCAB (49.3%), 468 as
      OPCAB (46.8%) and 39 originally scheduled OPCAB operations were converted to
      ONCAB (7.7% of originally scheduled OPCAB patients or 3.9% of total number of
      CABG). Reasons for conversions were: mild to severe hemodynamic instability--28
      (71.8%); poor vessels or difficult graft revision--11 (28.2%). Patients converted
      because of technical difficulty or mild hemodynamic instability behaved as
      regular ONCAB patients. In the 9 patients who were emergently converted due to
      cardiac arrest or ventricular fibrillation, 3 patients had stroke and 3 severe
      myocardial ischemia requiring intraaortic balloon pump. It is of great importance
      to keep conversions to CPB due to cardiac arrest at a low level. The serious
      complications seen in such patients can significantly impede the overall benefits
      of a successful OPCAB program.

PMID- 18816262
TI  - Importance of isolation and biotypization of Gardnerella vaginalis in diagnosis
      of bacterial vaginosis.
AB  - The natural habitat of Gardnerella vaginalis is a vagina since it could be
      located among 69% of women who have no signs of vaginal infection and in the
      vagina of as many as 13.5% girls. G. vaginalis is almost certainly identified
      among women diagnosed with bacterial vaginosis as well as in the urethra of their
      sexual partner. The increase in prevalence and concentration of G. vaginalis
      among patients diagnosed with this syndrome confirms that G. vaginalis plays a
      significant role in its pathogenesis. In our research, based on Amsel criteria
      for three or more clinical signs of bacterial vaginosis, it was diagnosed in
      20.5% of women with subjective problems of vaginal infection, and in 48.80% of
      women with subjective symptoms characteristic of this disease. G. vaginalis was
      isolated from vaginal secretion of women without clinical signs characteristic of
      bacterial vaginosis. In 2.58% of cases it was solitary, while in 1.28% it was
      found in combination with other aerobic and anaerobic bacteria and, in 1.28%
      women combined with Candida albicans. The isolation of G. vaginalis was
      significantly increased (p<0.05) in the group of women with clinical signs of
      bacterial vaginosis in comparison to the group of women without these signs.
      Frequent recurrence of bacterial vaginosis, which is found in 20-30% of women
      within a three months treatment, is explained as reinfection with other biotype
      of G. vaginalis, different from a source biotype or as a consequence of wrong
      treatment. Following Piot biotype scheme, biotypes 2., 3. and 7. G. vaginalis are
      significantly more often isolated from women who suffer from bacterial vaginosis.
      Biotype 7. G. vaginalis, isolated from the group of women without clinical signs
      of bacterial vaginosis, accounted for 2.58% cases. Following Benit biotype
      scheme, biotypes IVa, IVc and IIc were identified in 12.90% cases, while biotypes
      IIIa, IIa, Ia, IVb, IIb were found in 6.45% cases. Lipase-positive isolates of G.
      vaginalis were significantly more frequently accompanied by the syndrome of
      bacterial vaginosis.

PMID- 18816263
TI  - The synthesis and antimicrobial activity of some 4-hydroxycoumarin derivatives.
AB  - Due to exceptional reactivity of 4-hydroxycoumarin, the synthesis of new coumarin
      derivatives of dimer and tetramer type has been carried out. The synthesis was
      carried out from 4-hydroxycoumarin and various aromatic aldehydes. In this way,
      compounds of the dimer 3,3'-(benzilidene)bis (4-hydroxycoumarin) type, as well as
      of the tetramer 3,3',3'',3'''-(1,4-dimethylenphenyl)tetra (4-hydroxycoumarin)
      type were prepared. The newly synthesized derivatives contain different
      functional groups, and as such they could exhibit microbiological activity.
      Therefore, we tested the microbiological activity of these derivatives on various
      species of bacteria and fungi. The tested compounds have shown different activity
      in terms of growth inhibition of microorganisms. Newly synthesized derivatives
      exhibit antibacterial activities, manifested as growth inhibition on Gram
      positive bacteria types (Bacillus, Staphylococcus), while the activity against
      Candida was much weaker. The same compound did not show any antimicrobial
      activity against two Gram-negative bacteria types (Escherichia coli, Pseudomonas
      aeruginosa). The compound 1 showed the best microbiological activity. The
      obtained results confirmed its good antibacterial and antimycotic activities
      against different microorganisms.

PMID- 18816264
TI  - Amino-terminal pro-brain natriuretic peptid in prediction of left ventricular
      ejection fraction.
AB  - We aimed to evaluate levels of amino-terminal pro-brain natriuretic peptid (NT
      proBNP) in prediction of left ventricular ejection fraction (LVEF) in heart
      failure patients. Prospective study on 60 consecutive patients with symptoms and
      signs of heart failure was performed. Blood samples for NT-proBNP analysis was
      taken from all test subjects and echocardiography was also done in all of them.
      According to LVEF value, patients were divided into four groups; those with
      <or=30%, 31 to 39%, 40 to 49% and >or=50%. NT-proBNP values correlated with LVEF
      value. Regression analysis was used to evaluate how well NT-proBNP values predict
      LVEF. We used Receiver Operating Characteristic Curve calculation to evaluate
      diagnostic performance of NT-proBNP in estimation of LVEF. Average value of NT
      proBNP in test group was 3191.69+/-642.89 pg/ml (p<0.001). Average value of NT
      proBNP decreased with higher LVEF categories with significant (p<0.001) and high
      negative correlation (r= -0,75). Stepwise multivariate linear regression analysis
      showed that logarithmic value of NT-proBNP was excellent predictor of LVEF value
      (p<0.05). Model equation based on regression analysis was LVEF=88.645-15.311 x
      log (NT-proBNP). Predictive model for LVEF yielded from regression analysis had
      sensitivities of 98% and 81%, specificities of 20% and 90%, positive predictive
      values of 86% and 78% and negative predictive values of 67% and 92% for
      predicting patients with LVEF<50% and LVEF<40%, respectively. There was negative
      linear correlation between NT-proBNP and LVEF. NT-proBNP was excellent predictor
      of LVEF value (p<0.05).

PMID- 18816265
TI  - Phenotype manifestations of polysomy X at males.
AB  - Klinefelter Syndrome is the most frequent form of male hypogonadism. It is an
      endocrine disorder based on sex chromosome aneuploidy. Infertility and
      gynaecomastia are the two most common symptoms that lead to diagnosis. Diagnosis
      of Klinefelter syndrome is made by karyotyping. Over 20 years period (1985-2004)
      124 patients have been sent to "Center for Human Genetics" of Faculty of Medicine
      in Sarajevo from different medical centres within Federation of Bosnia and
      Herzegovina with diagnosis suspecta Klinefelter syndrome, azoospermia, sterilitas
      primaria and hypogonadism for cytogenetic evaluation. Normal karyotype was found
      in 99 (79.8%) subjects, and karyotype was changed in 25 (20.2%) subjects.
      Polysomy X was found in 14 (11.3%) examinees. Polysomy X was expressed at the age
      of sexual maturity in the majority of the cases. Our results suggest that
      indication for chromosomal evaluation needs to be established at a very young
      age.

PMID- 18816266
TI  - Comparative study of operative treatment [corrected] of varicose veins according
      to the Klapp and Smetana method versus Myers method.
AB  - Venous abnormalities in lower extremities are among the most frequent disorders
      that affects general population with significant morbidity and mortality.
      Usually, the problem consists of a mild form of varicose veins and
      teleangiectasis. Treatment in this stage of disease is highly recommended since
      progression can lead to chronic venous insufficiency and chronic disability with
      very few effective treatment options. The most effective and popular treatment of
      varicose veins is operative treatment; specifically two different operative
      procedures: method according to Myers and method according to Klapp and Smetana.
      We designed this study in order to determine which method is superior based on
      clinical parameters and patients satisfaction. Our evidence strongly support
      clinical superiority, as well as patient satisfaction, of Klapp and Smetana
      method.

PMID- 18816267
TI  - Control techniques for Culicoides biting midges and their application in the U.K.
      and northwestern Palaearctic.
AB  - The recent emergence of bluetongue virus (Reoviridae: Orbivirus) (BTV) in
      northern Europe, for the first time in recorded history, has led to an urgent
      need for methods to control the disease caused by this virus and the midges that
      spread it. This paper reviews various methods of vector control that have been
      employed elsewhere and assesses their likely efficacy for controlling vectors of
      BTV in northern Europe. Methods of controlling Culicoides spp. (Diptera:
      Ceratopogonidae) have included: (a) application of insecticides and pathogens to
      habitats where larvae develop; (b) environmental interventions to remove larval
      breeding sites; (c) controlling adult midges by treating either resting sites,
      such as animal housing, or host animals with insecticides; (d) housing livestock
      in screened buildings, and (e) using repellents or host kairomones to lure and
      kill adult midges. The major vectors of BTV in northern Europe are species from
      the Culicoides obsoletus (Meigen) and Culicoides pulicaris (L.) groups, for which
      there are scant data on breeding habits, resting behaviour and host-oriented
      responses. Consequently, there is little information on which to base a rational
      strategy for controlling midges or for predicting the likely impact of
      interventions. However, data extrapolated from the results of vector control
      operations conducted elsewhere, combined with some assessment of how acceptable
      or not different methods may be within northern Europe, indicate that the
      treatment of livestock and animal housing with pyrethroids, the use of midge
      proofed stabling for viraemic or high-value animals and the promotion of good
      farm practice to at least partially eliminate local breeding sites are the best
      options currently available. Research to assess and improve the efficacy of these
      methods is required and, in the longer term, efforts should be made to develop
      better bait systems for monitoring and, possibly, controlling midges. All these
      studies will need better methods of analysing the ecology and behaviour of midges
      in the field than are currently in use. The paucity of control options and basic
      knowledge serve to warn us that we must be better prepared for the possible
      emergence of other midge-borne diseases, particularly African horse sickness.

PMID- 18816268
TI  - Insecticide resistance in the horn fly: alternative control strategies.
AB  - The horn fly, Haematobia irritans (Linnaeus 1758) (Diptera: Muscidae) is one of
      the most widespread and economically important pests of cattle. Although
      insecticides have been used for fly control, success has been limited because of
      the development of insecticide resistance in all countries where the horn fly is
      found. This problem, along with public pressure for insecticide-free food and the
      prohibitive cost of developing new classes of compounds, has driven the
      investigation of alternative control methods that minimize or avoid the use of
      insecticides. This review provides details of the economic impact of horn flies,
      existing insecticides used for horn fly control and resistance mechanisms.
      Current research on new methods of horn fly control based on resistant cattle
      selection, semiochemicals, biological control and vaccines is also discussed.

PMID- 18816269
TI  - Effect of dengue vector control interventions on entomological parameters in
      developing countries: a systematic review and meta-analysis.
AB  - The aim of this review was to compare the effects of different dengue vector
      control interventions (i.e. biological control, chemical control, environmental
      management and integrated vector management) with respect to the following
      entomological parameters: Breteau index (BI), container index (CI), and house
      index (HI). We systematically searched PubMed, ISI Web of Science, Science
      Direct, the Dengue Bulletin of the World Health Organization and reference lists
      of retrieved articles on dengue vector control interventions in developing
      countries. We extracted data on the effectiveness of different dengue vector
      control interventions (defined as the relative reduction of an entomological
      measure caused by the intervention compared with the control or pre-intervention
      phase) and calculated a measure of combined relative effectiveness, with 95%
      confidence intervals (95% c.i.). We identified 56 publications covering 61 dengue
      vector control interventions. Integrated vector management was found to be the
      most effective method to reduce the CI, HI and BI, resulting in random combined
      relative effectiveness values of 0.12 (95% c.i. 0.02-0.62), 0.17 (95% c.i. 0.02
      1.28) and 0.33 (95% c.i. 0.22-0.48), respectively. Environmental management
      showed a relatively low effectiveness of 0.71 (95% c.i. 0.55-0.90) for the BI,
      0.49 (95% c.i. 0.30-0.79) for the CI and 0.43 (95% c.i. 0.31-0.59) for the HI.
      Biological control (relative effectiveness for the CI: 0.18) usually targeted a
      small number of people (median population size: 200; range 20-2500), whereas
      integrated vector management focused on larger populations (median: 12 450;
      range: 210-9 600 000). In conclusion, dengue vector control is effective in
      reducing vector populations, particularly when interventions use a community
      based, integrated approach, which is tailored to local eco-epidemiological and
      sociocultural settings and combined with educational programmes to increase
      knowledge and understanding of best practice. New research should assess the
      density-dependent effectiveness of each control measure in order to estimate
      whether reducing vector numbers has an impact on dengue transmission when
      populations are at a critical threshold.

PMID- 18816270
TI  - Structure of some East African Glossina fuscipes fuscipes populations.
AB  - Glossina fuscipes fuscipes Newstead 1910 (Diptera: Glossinidae) is the primary
      vector of human sleeping sickness in Kenya and Uganda. This is the first report
      on its population structure. A total of 688 nucleotides of mitochondrial
      ribosomal 16S2 and cytochrome oxidase I genes were sequenced. Twenty-one variants
      were scored in 79 flies from three geographically diverse natural populations.
      Four haplotypes were shared among populations, eight were private and nine were
      singletons. The mean haplotype and nucleotide diversities were 0.84 and 0.009,
      respectively. All populations were genetically differentiated and were at
      demographic equilibrium. In addition, a longstanding laboratory culture
      originating from the Central African Republic (CAR-lab) in 1986 (or before) was
      examined. Haplotype and nucleotide diversities in this culture were 0.95 and
      0.012, respectively. None of its 27 haplotypes were shared with the East African
      populations. A first approximation of relative effective population sizes was
      Uganda > CAR-lab > Kenya. It was concluded that the structure of G. f. fuscipes
      populations in East Africa is localized.

PMID- 18816271
TI  - Rates of bluetongue virus transmission between Culicoides sonorensis and sheep.
AB  - Two experiments were undertaken to estimate the transmission rates of bluetongue
      virus (BTV) serotype 1 between a biting midge vector, Culicoides sonorensis
      (Wirth & Jones) (Ceratopogonidae), and a natural host, sheep. In an experiment to
      measure the transmission rate from vector to host (V-->H), six batches of one,
      five and 20 intrathoracically infected midges were fed on a total of 18
      bluetongue (BT)-naive sheep. The sheep were then monitored for 21 days for
      clinical signs of BT, viraemia and antibody response. All sheep fed on by five or
      20 midges and five of six sheep fed on by just one midge showed signs of BT, were
      viraemic and developed antibody. The sixth sheep fed on by a single infected
      midge did not show signs of BT or have detectable viraemia; it did, however,
      develop a weak antibody response. A bite from a single infected midge is
      therefore able to transmit BTV to naive sheep with 80-100% efficiency. Sheep fed
      upon by larger numbers of infected midges took less time to reach maximum
      viraemia and developed stronger antibody responses. Sheep exposed to greater
      amounts of BTV in feeding midges developed a higher level of viraemia and
      stronger antibody responses. In a second experiment to measure the transmission
      rate from host to vector (H-->V), batches of up to 500 uninfected female C.
      sonorensis fed every 1-2 days on two experimentally infected sheep during the
      course of infection. Of 3929 engorged midges that were individually titrated
      after surviving the extrinsic incubation period, only 23 (0.6%) were infected
      with BTV. Viraemia in the sheep extended for up to 19 days post-inoculation. No
      infected midges, however, were detected from 14 days post-infection.

PMID- 18816272
TI  - Trends in ixodid tick abundance and distribution in Great Britain.
AB  - The popular, but rarely documented, view in Britain is that ticks have increased
      in distribution and abundance over recent years. To assess this, we gathered
      evidence for changes in tick distribution and abundance by distributing a survey
      questionnaire throughout Britain and by analysing trends in the prevalence of
      tick infestation on red grouse chicks Lagopus lagopus scoticus Latham
      (Galliformes: Tetranoidae), gathered over 19 years at three Scottish sites, and
      on deer (Cetartiodactyla: Cervidae) culled over 11 years on 26 Ministry of
      Defence (MoD) estates. Based on the survey, the current known distribution of
      Ixodes ricinus Linnaeus (Acari: Ixodidae) has expanded by 17% in comparison with
      the previously known distribution. The survey indicated that people perceive
      there to be more ticks today than in the past at 73% of locations throughout
      Britain. Reported increases in tick numbers coincided spatially with perceived
      increases in deer numbers. At locations where both tick and deer numbers were
      reported to have increased, these perceived changes occurred at similar times,
      raising the possibility of a causal link. At other locations, tick numbers were
      perceived to have increased despite reported declines in deer numbers. The
      perceptions revealed by the survey were corroborated by quantitative data from
      red grouse chicks and culled deer. Tick infestation prevalence increased over
      time on all grouse moors and 77% of MoD estates and decreased at six locations.

PMID- 18816273
TI  - An assessment of the effect of data partitioning on the performance of modelling
      algorithms for habitat suitability for ticks.
AB  - A comparison of the performance of five modelling methods using presence/absence
      (generalized additive models, discriminant analysis) or presence-only (genetic
      algorithm for rule-set prediction, ecological niche factor analysis, Gower
      distance) data for modelling the distribution of the tick species Boophilus
      decoloratus (Koch, 1844) (Acarina: Ixodidae) at a continental scale (Africa)
      using climate data was conducted. This work explicitly addressed the usefulness
      of clustering using the normalized difference vegetation index (NDVI) to split
      original records and build partial models for each region (cluster) as a method
      of improving model performance. Models without clustering have a consistently
      lower performance (as measured by sensitivity and area under the curve [AUC]),
      although presence/absence models perform better than presence-only models. Two
      cluster-related variables, namely, prevalence (commonness of tick records in the
      cluster) and marginality (the relative position of the climate niche occupied by
      the tick in relation to that available in the cluster) greatly affect the
      performance of each model (P < 0.05). Both sensitivity and AUC are better for
      NDVI-derived clusters where the tick is more prevalent or its marginality is low.
      However, the total size of the cluster or its fragmentation (measured by
      Shannon's evenness index) did not affect the performance of models. Models
      derived separately for each cluster produced the best output but resulted in a
      patchy distribution of predicted occurrence. The use of such a method together
      with weighting procedures based on prevalence and marginality as derived from
      populations at each cluster produced a slightly lower predictive performance but
      a better estimation of the continental distribution of the tick. Therefore,
      cluster-derived models are able to effectively capture restricting conditions for
      different tick populations at a regional level. It is concluded that data
      partitioning is a powerful method with which to describe the climate niche of
      populations of a tick species, as adapted to local conditions. The use of this
      methodology greatly improves the performance of climate suitability models.

PMID- 18816274
TI  - Reduced susceptibility to DDT in field populations of Anopheles quadriannulatus
      and Anopheles arabiensis in Malawi: evidence for larval selection.
AB  - Bioassays for insecticide resistance in adult mosquitoes were conducted on
      samples of Anopheles gambiae Giles s.l. (Diptera: Culicidae) species collected as
      larvae from breeding sites in the lower Shire Valley, Malawi. The results
      indicate full susceptibility to permethrin, deltamethrin and malathion, but
      reduced susceptibility to DDT in one sample from Thom (LT(50) of 8.39 min for
      females and 25.09 min for males). Polymerase chain reaction-based species
      identification of the mosquitoes assayed revealed a mixture of Anopheles
      arabiensis Patton and Anopheles quadriannulatus (Theobold). The LT(50) did not
      differ significantly between species. Genotyping of the L1014F and L1014S kdr
      alleles showed all mosquito specimens to be homozygous wild type; thus the
      reduced susceptibility detected is not attributable to target site insensitivity
      and instead is likely to be metabolic in nature. Anopheles quadriannulatus is
      characteristically zoophagic and exophilic. Indeed, of 82 Anopheles collected
      through knockdown collections within dwellings, only one was An. quadriannulatus
      and the rest were An. arabiensis. They are unlikely, therefore, to have been
      exposed to selection pressure arising from insecticide-treated net usage or to
      DDT indoor residual spraying. Therefore, it is suggested that this example of
      reduced susceptibility to DDT in An. quadriannulatus reflects selection in the
      larval stages.

PMID- 18816275
TI  - In vitro efficacy of over-the-counter botanical pediculicides against the head
      louse Pediculus humanus var capitis based on a stringent standard for mortality
      assessment.
AB  - Infestation of the head louse Pediculus humanus var capitis DeGeer (Phthiraptera:
      Pediculidae) is an important public health problem in Australia, with up to a
      third of children infested in some primary schools. Insecticide resistance and
      inadequate attention to the application instructions of topical pediculicides are
      common reasons for treatment failure. This study evaluated six popular Australian
      over-the-counter products against head lice, primarily comprised of different
      botanical extracts, and compared them with permethrin 1% (Quellada) and a non
      treatment control in order to assess their in vitro efficacy. We also assessed
      commonly used criteria for evaluating pediculicide efficacy in vitro. All tested
      products failed to demonstrate high levels of efficacy with the exception of Tea
      Tree Gel((R)), which outperformed 1% permethrin. Permethrin had a high level of
      efficacy, but using stringent criteria 18% of lice were not dead at 3 h,
      indicating some resistance to Quellada. Commonly used less stringent criteria
      were shown to overestimate mortality of head lice as a result of the protective
      phenomenon of stasis or sham death observed in exposed lice that may recover
      after some time. Using two different levels of stringency resulted in different
      rankings of efficacy for most products, with the exception of the first ranked
      product, Tea Tree Gel. Rankings of efficacy also varied over time, even within
      the different assessment criteria. Government regulatory agencies should require
      standard in vitro tests using stringent mortality criteria, with an observation
      period of >or= 6 h, to determine the efficacy of new pediculicides, and only
      products that cause a minimum mortality rate (e.g. 80%) in head lice collected
      from the target population should be licensed for sale.

PMID- 18816276
TI  - Environmental and demographic factors determining the spatial distribution of
      Triatoma guasayana in peridomestic and semi-sylvatic habitats of rural
      northwestern Argentina.
AB  - Triatoma guasayana (Wygodzinsky & Abalos), a sylvatic vector of Chagas' disease,
      occurs in natural and peridomestic habitats of the dry Chaco region of Argentina,
      Bolivia and Paraguay. Ten-year retrospective spatial analyses of peridomestic T.
      guasayana abundance in the rural community of Amama were expanded to the
      neighbouring community of Trinidad in northwestern Argentina. The distribution of
      T. guasayana in domiciles, peridomiciles (storerooms, chicken coops and corrals)
      and natural habitats (bromeliads, dry cacti and logs) around houses (i.e. 'semi
      sylvatic' habitats) was analysed. The distribution of the 316 T. guasayana
      specimens collected in domestic and peridomestic sites during 1993-2002 was
      significantly clustered in both communities. Searches confirmed that the spatial
      distribution of semi-sylvatic and peridomestic T. guasayana was determined by the
      joint effects of the local abundance of goats and the density of semi-sylvatic
      habitats. The integration of detailed entomological and demographic longitudinal
      data with geographic information system data, high-resolution satellite imagery,
      appropriate spatial and temporal analyses and field observations allowed us to
      infer the underlying processes determining the distribution of T. guasayana in
      rural communities. This approach may be applied to other sylvatic and
      peridomestic vectors of Chagas' disease in order to identify high-risk areas for
      targeted control or environmental management.

PMID- 18816277
TI  - Identification of the intermediate hosts of Habronema microstoma and Habronema
      muscae under field conditions.
AB  - A polymerase chain reaction (PCR)-based assay was used for the specific detection
      of Habronema microstoma and Habronema muscae (Nematoda, Spirurida) in order to
      identify the intermediate hosts of both nematode species under field conditions.
      A total of 1087 netted and 165 laboratory-bred flies were tested. Flies were
      identified as Musca domestica Linnaeus 1758, Musca autumnalis De Geer 1776,
      Haematobia irritans (Linnaeus 1758), Haematobia titillans (De Geer 1907) and
      Stomoxys calcitrans (Linnaeus 1758) (Muscidae). Genomic DNA was extracted from
      pools of fly heads, thoraces and abdomens, and 703 samples were subjected to a
      duplex two-step semi-nested PCR assay to specifically detect diagnostic regions
      within the ribosomal ITS2 sequence of both H. microstoma and H. muscae. Stomoxys
      calcitrans specimens were positive for H. microstoma DNA and M. domestica
      specimens were positive for H. muscae DNA. In particular, PCR-positive samples
      derived from both farm-netted and laboratory-bred flies. The present study
      represents the first evidence of the vectorial competence of different fly
      species as intermediate hosts of Habronema stomachworms under field conditions.
      We discuss the roles of S. calcitrans and M. domestica in transmitting H.
      microstoma and H. muscae.

PMID- 18816278
TI  - Analysis of the activity patterns of two sympatric sandfly siblings of the
      Lutzomyia longipalpis species complex from Brazil.
AB  - Lutzomyia longipalpis s.l. (Lutz & Neiva) (Diptera: Psychodidae) is the main
      vector of visceral leishmaniasis in Latin America. Differences in copulation
      songs, pheromones and molecular markers show that L. longipalpis is a species
      complex in Brazil. The patterns of activity of insect vectors are important in
      disease transmission. In addition, differences in activity rhythms have a
      potential role as a temporal reproductive isolation mechanism in closely related
      species. We compared the activity patterns of males and females of two sympatric
      species of the Longipalpis complex from Sobral (Ceara State, Brazil) in
      controlled laboratory conditions. We observed small but significant differences
      between the two species in the activity phase in both males and females.

PMID- 18816279
TI  - Lasting false beliefs and their behavioral consequences.
AB  - False beliefs and memories can affect people's attitudes, at least in the short
      term. But can they produce real changes in behavior? This study explored whether
      falsely suggesting to subjects that they had experienced a food-related event in
      their childhood would lead to a change in their behavior shortly after the
      suggestion and up to 4 months later. We falsely suggested to 180 subjects that,
      as children, they had gotten ill after eating egg salad. Results showed that,
      after this manipulation, a significant minority of subjects came to believe they
      had experienced this childhood event even though they had initially denied having
      experienced it. This newfound autobiographical belief was accompanied by the
      intent to avoid egg salad, and also by significantly reduced consumption of egg
      salad sandwiches, both immediately and 4 months after the false suggestion. The
      false suggestion of a childhood event can lead to persistent false beliefs that
      have lasting behavioral consequences.

PMID- 18816280
TI  - Death without God: religious struggle, death concerns, and depression in the
      terminally ill.
AB  - Religious worldviews often provide comfort near the end of life, but they can
      cause distress if life circumstances are perceived as evidence of God's disfavor.
      This study, the first to test terror management theory (TMT) with terminally ill
      participants, examined the hypothesis that concerns about death mediate the
      relationship between religious struggle (and religious comfort) and depression in
      the terminally ill. Ninety-eight patients with end-stage congestive heart failure
      (CHF) completed measures of religious comfort, religious struggle, belief in an
      afterlife, concerns about death, and depression. In separate hierarchical linear
      regression models that controlled for degree of belief in an afterlife, death
      concerns fully mediated the relationships between religious struggle and
      depression and between religious comfort and depression. These findings suggest
      that religious struggle is a breakdown in the terror management system that
      leaves the individual vulnerable to the terror of death, and that properly
      functioning religious worldviews offer comfort by buffering the individual
      against death concerns.

PMID- 18816281
TI  - Chinese children excel on novel mathematics problems even before elementary
      school.
AB  - Kindergartners in China showed greater numerical knowledge than their age peers
      in the United States, not only when tested with arithmetic problems, which
      Chinese parents present to their children more often than U.S. parents do, but
      also when tested with number-line estimation problems, which were novel to the
      children in both countries. The Chinese kindergartners' number-line estimates
      were comparable to those of U.S. children 1 to 2 years more advanced in school.
      Individual differences in arithmetic and number-line-estimation performance were
      positively correlated within each country. These results indicate that
      performance differences between Chinese and U.S. children on both practiced and
      unpracticed mathematical tasks are substantial even before the children begin
      elementary school.

PMID- 18816282
TI  - Submitting to defeat: social anxiety, dominance threat, and decrements in
      testosterone.
AB  - Although theory suggests a link between social anxiety and social dominance,
      direct empirical evidence for this link is limited. The present experiment tested
      the hypothesis that socially anxious individuals, particularly men, would respond
      to a social-dominance threat by exhibiting decrements in their testosterone
      levels, an endocrinological change that typically reflects pronounced social
      submission in humans and other animals. Participants were randomly assigned to
      either win or lose a rigged face-to-face competition with a confederate. Although
      no zero-order relationship between social anxiety and level of testosterone was
      observed, testosterone levels showed a pronounced drop among socially anxious men
      who lost the competition. No significant changes were observed in nonanxious men
      or in women. This research provides novel insight into the nature and
      consequences of social anxiety, and also illustrates the utility of integrating
      social psychological theory with endocrinological approaches to psychological
      science.

PMID- 18816283
TI  - When the referee sees red...

PMID- 18816284
TI  - How to accurately detect autobiographical events.
AB  - We describe a new method, based on indirect measures of implicit autobiographical
      memory, that allows evaluation of which of two contrasting autobiographical
      events (e.g., crimes) is true for a given individual. Participants were requested
      to classify sentences describing possible autobiographical events by pressing one
      of two response keys. Responses were faster when sentences related to truly
      autobiographical events shared the same response key with other sentences
      reporting true events and slower when sentences related to truly autobiographical
      events shared the same response key with sentences reporting false events. This
      method has possible application in forensic settings and as a lie-detection
      technique.

PMID- 18816285
TI  - Sleep preferentially enhances memory for emotional components of scenes.
AB  - Central aspects of emotional experiences are often well remembered at the expense
      of background details. Previous studies of such memory trade-offs have focused on
      memory after brief delays, but little is known about how these components of
      emotional memories change over time. We investigated the evolution of memory for
      negative scenes across 30 min, 12 daytime hours spent awake, and 12 nighttime
      hours including sleep. After 30 min, negative objects were well remembered at the
      expense of information about their backgrounds. Time spent awake led to
      forgetting of the entire negative scene, with memories of objects and their
      backgrounds decaying at similar rates. Sleep, in contrast, led to a preservation
      of memories of negative objects, but not their backgrounds, a result suggesting
      that the two components undergo differential processing during sleep. Memory for
      a negative scene develops differentially across time delays containing sleep and
      wake, with sleep selectively consolidating those aspects of memory that are of
      greatest value to the organism.

PMID- 18816286
TI  - When hurt will not heal: exploring the capacity to relive social and physical
      pain.
AB  - Recent discoveries suggest that social pain is as real and intense as physical
      pain, and that the social-pain system may have piggybacked on the brain structure
      that had evolved earlier for physical pain. The present study examined an
      important distinction between social and physical pain: Individuals can relive
      and reexperience social pain more easily and more intensely than physical pain.
      Studies 1 and 2 showed that people reported higher levels of pain after reliving
      a past socially painful event than after reliving a past physically painful
      event. Studies 3 and 4 found, in addition, that people performed worse on
      cognitively demanding tasks after they relived social rather than physical pain.
      Implications for research on social pain and theories about social pain are
      discussed.

PMID- 18816287
TI  - A wrinkle in time: asymmetric valuation of past and future events.
AB  - A series of studies shows that people value future events more than equivalent
      events in the equidistant past. Whether people imagined being compensated or
      compensating others, they required and offered more compensation for events that
      would take place in the future than for identical events that had taken place in
      the past. This temporal value asymmetry (TVA) was robust in between-persons
      comparisons and absent in within-persons comparisons, which suggests that
      participants considered the TVA irrational. Contemplating future events produced
      greater affect than did contemplating past events, and this difference mediated
      the TVA. We suggest that the TVA, the gain-loss asymmetry, and hyperbolic time
      discounting can be unified in a three-dimensional value function that describes
      how people value gains and losses of different magnitudes at different moments in
      time.

PMID- 18816288
TI  - Search in external and internal spaces: evidence for generalized cognitive search
      processes.
AB  - There is compelling molecular and behavioral evidence that goal-directed
      cognition is an evolutionary descendant of spatial-foraging behavior. Across
      animal species, similar dopaminergic processes modulate between exploratory and
      exploitative foraging behaviors and control attention. Consequently, we
      hypothesized that spatial-foraging activity could prime attentional cognitive
      activity. We examined how searching in physical space influences subsequent
      search in abstract cognitive space by presenting participants with a spatial
      foraging task followed by a repeated Scrabble task involving search for words
      that could be made from letter sets. Participants who searched through clumpier
      distributions in space behaved as if words were more densely clumped in the
      Scrabble task. This was not a function of arousal, but was consistent with
      predictions of optimal-foraging theory. Furthermore, individual differences in
      exploratory search were conserved across the two types of tasks. Along with the
      biological evidence, our results support the idea that there are generalized
      cognitive search processes.

PMID- 18816289
TI  - From sucker to saint: moralization in response to self-threat.
AB  - When people's rationality and agency are implicitly called into question by the
      more expedient behavior of others, they sometimes respond by feeling morally
      superior; this is referred to as the sucker-to-saint effect. In Experiment 1,
      participants who completed a tedious task and then saw a confederate quit the
      same task elevated their own morality over that of the confederate, whereas
      participants who simply completed the task or simply saw the confederate quit did
      not. In Experiment 2, this effect was eliminated by having participants
      contemplate a valued personal quality before encountering the rebellious
      confederate, a result suggesting a role for self-threat in producing
      moralization. These studies demonstrate that moral judgments can be more deeply
      embedded in judges' immediate social contexts-and driven more by motivations to
      maintain self-image-than is typically appreciated in contemporary moral
      psychology research. Rather than uphold abstract principles of justice, moral
      judgment may sometimes just help people feel a little less foolish.

PMID- 18816290
TI  - I am too just like you: nonconscious mimicry as an automatic behavioral response
      to social exclusion.
AB  - Research across various disciplines has demonstrated that social exclusion has
      devastating psychological, emotional, and behavioral consequences. Excluded
      individuals are therefore motivated to affiliate with others, even though they
      may not have the resources, cognitive or otherwise, to do so. The current
      research explored whether nonconscious mimicry of other individuals-a low-cost,
      low-risk, automatic behavior-might help excluded individuals address threatened
      belongingness needs. Experiment 1 demonstrated that excluded people mimic a
      subsequent interaction partner more than included people do. Experiment 2 showed
      that individuals excluded by an in-group selectively (and nonconsciously) mimic a
      confederate who is an in-group member more than a confederate who is an out-group
      member. The relationship between exclusion and mimicry suggests that there are
      automatic behaviors people can use to recover from the experience of being
      excluded. In addition, this research demonstrates that nonconscious mimicry is
      selective and sensitive to context.

PMID- 18816291
TI  - Motion, not masking, provides the medium for feature attribution.
AB  - Understanding the dynamics of how separate features combine to form holistic
      object representations is a central problem in visual cognition. Feature
      attribution (also known as feature transposition and feature inheritance) refers
      to the later of two stimuli expressing the features belonging to the earlier one.
      Both visual masking and apparent motion are implicated in feature attribution. We
      found that when apparent motion occurs without masking, it correlates positively
      with feature attribution. Moreover, when apparent motion occurs with masking,
      feature attribution remains positively correlated with apparent motion after the
      contribution of masking is factored out, but does not correlate with masking
      after the contribution of apparent motion is similarly factored out. Hence,
      motion processes on their own provide the effective medium for feature
      attribution. Our results clarify the dynamics of feature binding in the formation
      of integral and unitary object representations in human vision.

PMID- 18816292
TI  - Thymoquinone ameliorates renal oxidative damage and proliferative response
      induced by mercuric chloride in rats.
AB  - We tested the hypothesis if thymoquinone (2-isopropyl-5-methyl-1,4-benzoquinone)
      could ameliorate renal oxidative damage and proliferative response induced by
      mercuric chloride (HgCl2) in rats. HgCl2 (3 mg/kg) was administered
      subcutaneously to each one of two groups of rats: (i) HgCl2-thymoquinone group
      that received thymoquinone (10 mg/kg/day); and (ii) HgCl2 group that received
      vehicle instead of thymoquinone. A third group of rats was reserved as control
      group. Rats were killed 24, 48 and 72 hr after HgCl2 administration for
      histological and biochemical studies. Our findings show that treatment with
      thymoquinone offers imperative protection from HgCl2-induced nephrotoxicity. The
      deterioration of antioxidant enzymes, increment of serum creatinine and
      histological damage caused by HgCl2 are markedly improved by thymoquinone
      treatment. Apoptosis and proliferative reactions are also reduced. The maximal
      protection offered by thymoquinone treatment was particularly noticeable 48 and
      72 hr after administration of the toxic agent at the time when histological
      damage, renal cell apoptosis and proliferative reactions reached their maximum.
      These observations may be attributed partially to the antioxidant effect of
      thymoquinone and suggest that it may be a clinically valuable agent in the
      prevention of acute renal failure caused by inorganic mercury intoxication.

PMID- 18816293
TI  - The influence of acetylcholinesterase reactivators on selected hepatic functions
      in rats.
AB  - The aim of our study was to evaluate the impact of acetylcholinesterase
      reactivators--K027 [1-(4-carbamoyl pyridinium)-3-(4-hydroxyiminomethyl
      pyridinium) propane dibromide], HI-6 [1-(4-carbamoylpyridinium)-3-(2-hydroxyimino
      methylpyridinium) oxapropane dichloride] and obidoxime [1,3-bis(4
      hydroxyiminomethyl pyridinium)oxapropane dichloride] on hepatic functions in
      vivo. Male Wistar rats were randomly divided to seven groups and intramuscularly
      administered with saline and acetylcholinesterase reactivators (K027, HI-6 and
      obidoxime) at doses of 5% LD(50) and 50% LD(50). Liver tissue samples were taken
      24 hr after administration. Histochemical detection of lipid droplets and
      immunohistochemical detection of multidrug resistance protein 2 (Mrp2) were
      provided. Lipid droplet count in rat liver did not show any significant
      differences in animals administered with K027, HI-6 and obidoxime in comparison
      with the control group. Mrp2 protein expression significantly decreased when
      animals were administered with K027 at a dose of 50% LD(50) and HI-6 and
      obidoxime at doses of 5% LD(50) and 50% LD(50), when compared to the controls. No
      statistical differences of Mrp2 expression were measured when animals were
      administered with K027 at a dose of 5% LD(50) in comparison with control animals.
      We found impaired hepatic transporter function after administration of HI-6,
      obidoxime and higher concentration of K027, which might be the underlying
      mechanism of acetylcholinesterase reactivators' hepatotoxicity.

PMID- 18816294
TI  - L-arginine inhibits isoproterenol-induced cardiac hypertrophy through nitric
      oxide and polyamine pathways.
AB  - Polyamines (putrescine, spermidine and spermine) are essential for cell growth
      and differentiation. Nitric oxide exhibits antihypertrophic functions and
      inhibits cardiac remodelling. However, the metabolism of polyamines and the
      potential interactions with nitric oxide in cardiac hypertrophy remain unclear.
      We randomly divided Wistar rats into four treatment groups: controls,
      isoproterenol (ISO), ISO and L-arginine, and L-arginine. Isoproterenol (5
      mg/kg/day, subcutaneously) and/or L-arginine (800 mg/kg/day, intraperitoneally)
      was administered once daily for 7 days. The expression of atrial natriuretic
      peptide mRNA was determined by reverse transcription-polymerase chain reaction,
      and fibrogenesis of heart was assessed by Van Gieson staining. Polyamines were
      measured with high-performance liquid chromatography, and plasma nitric oxide
      content and lactate dehydrogenase (LDH) activity were determined with a
      spectrophotometer. The expression levels of ornithine decarboxylase,
      spermidine/spermine N1-acetyltransferase (SSAT), endothelial nitric oxide
      synthase (eNOS) and inducible nitric oxide synthase (iNOS) were analysed by
      Western blot. Heart-to-body weight ratio, left ventricle-to-body weight ratio,
      atrial natriuretic peptide mRNA expression, collagen fibres and LDH activity were
      elevated, both ornithine decarboxylase and SSAT proteins were up-regulated, and
      total polyamines were increased in the group treated with ISO. Additionally, the
      expression of iNOS was up-regulated, eNOS was down-regulated, and nitric oxide
      levels were low. Notably, cotreatment with L-arginine reversed most of these
      changes except for SSAT expression,which was further up-regulated. We propose
      that increased polyamines and decreased nitric oxide are involved in cardiac
      hypertrophy induced by ISO and suggest that L-arginine pre-treatment can
      attenuate cardiac hypertrophy through the regulation of key enzymes of the
      polyamine and nitric oxide pathways.

PMID- 18816295
TI  - Effect of D256N and Y483D on propofol glucuronidation by human uridine 5'
      diphosphate glucuronosyltransferase (UGT1A9).
AB  - Uridine 5'-diphosphate glucuronosyltransferases (UGTs) are part of a major
      elimination pathway for endobiotics and xenobiotics. UGT1A9 is a UGT that
      catalyses the conjugation of endogenous oestrogenic and thyroid hormones,
      acetaminophen, SN-38 (an active metabolite of irinotecan) and phenols. UGT1A9 is
      the only isoform that catalyses the glucuronidation of propofol (2,6
      diisopropylphenol) in the liver. In the present study, we analysed polymorphisms
      of UGT1A9 in 100 healthy adult Japanese volunteers. A transversion of 766G > A
      resulting in the amino acid substitution of D256N was detected in exon 1. The
      allele frequency of D256N is 0.005. We investigated the effects of D256N and
      Y483D, which is located on the common exon of UGT1, on propofol glucuronidation
      by an in vitro expression study. The K(m) of wild-type, D256N and Y483D for
      propofol glucuronidation were 111.2, 43.6 and 64.5 microM, respectively. The
      V(max) of D256N and Y483D were 8.1% and 28.8%, and the efficiencies (V(max)/K(m))
      were 19.1% and 57.1% of the wild-type, respectively. For mycophenolic acid, 1
      naphthol and naringenin, the D256N variant lowered glucuronidation activity
      considerably, compared to Y483D. The V(max) value of D256N variant for
      mycophenolic acid was only 9.5% of the wild-type. This study shows the importance
      of D256N in differences between individuals concerning adverse effects of drugs
      that are catalysed primarily by UGT1A9. Carriers of D256N may be at risk of
      suffering adverse effects of propofol and other substrates that are primarily
      metabolized by UGT1A9.

PMID- 18816296
TI  - Cytoprotective effect of mangiferin on benzo(a)pyrene-induced lung carcinogenesis
      in swiss albino mice.
AB  - Antioxidants are one of the key players in tumourigenesis, and several natural
      and synthetic antioxidants have been shown to have anticancer effects. In the
      present investigation, the efficacy of mangiferin on the antioxidant status of
      benzo(a)pyrene-induced lung carcinogenesis in Swiss albino mice was assessed. The
      animals were divided into five groups. The animals in groups I and V were normal
      control and mangiferin control, respectively. Groups II, III and IV were
      administered with benzo(a)pyrene (50 mg/kg body weight, orally) for 4 weeks
      (twice a week) to induced lung carcinogenesis. Starting 1 week prior to
      benzo(a)pyrene administration, group III animals were treated with mangiferin
      (100 mg/kg body weight) in the diet for 18 weeks; 12 weeks after benzo(a)pyrene
      administration, group III animals were treated with mangiferin that continued
      until the end of the experiment period (18 weeks). At the end of the experiment
      period, the reactive oxygen species, glutathione and the activities of
      antioxidant enzymes were assessed in both lung and liver tissues. The levels of
      glutathione, superoxide dismutase, catalase, glutathione peroxidase, glutathione
      reductase, vitamin E and vitamin C were decreased in group II animals. However,
      in the mangiferin + benzo(a)pyrene-treated groups III and IV, the levels of GSH
      and the activities of antioxidant enzymes in both lung and liver were improved
      when compared with benzo(a)pyrene-induced group II animals. In addition, the
      finding that mangiferin decreased reactive oxygen species levels and enhanced
      antioxidant status suggests that this polyphenol might also be of value in the
      prevention of benzo(a)pyrene-induced lung carcinogenesis.

PMID- 18816297
TI  - Protective effect of extract from Paeonia lactiflora and Astragalus membranaceus
      against liver injury induced by bacillus Calmette-Guerin and lipopolysaccharide
      in mice.
AB  - Paeonia lactiflora and Astragalus membranaceus are two popular traditional
      Chinese medicines, commonly used in Chinese herb prescription to treat liver
      disease. The extract from the roots of P. lactiflora and A. membranaceus
      demonstrated better hepatoprotective activity than the herbs used individually as
      shown in our previous studies. The present study was carried out to investigate
      the effects of P. lactiflora and A. membranaceus extract on immunological liver
      injury in mice induced by Bacillus Calmette-Guerin and lipopolysaccharide
      (BCG/LPS) and to explore a possible mechanism. After administration of P.
      lactiflora and A. membranaceus (60, 120 and 240 mg/kg, intragastrically) daily
      for 10 days, the extract significantly reduced the degree of liver damage in
      BCG/LPS-induced liver injury, as well as the elevation of serum transaminase
      activities and level of nitric oxide in live injury mice. The extract also
      restored the decrease in superoxide dismutase and glutathione peroxidase
      activities and inhibited the formation of lipid peroxidative products. Moreover,
      P. lactiflora and A. membranaceus (60, 120 and 240 mg/kg, intragastrically)
      repressed high levels of tumour necrosis factor-alpha (TNF-alpha) and interleukin
      1 (IL-1) from peritoneal macrophages. In the primary cultured Kupffer cells, P.
      lactiflora and A. membranaceus also significantly decreased the production of TNF
      alpha and IL-1 in cells stimulated with LPS (5 microg/ml). These results suggest
      that P. lactiflora and A. membranaceus have a protective effect on BCG/LPS
      induced liver injury mice, which might be associated with the antioxidant
      properties, ability to reduce nitric oxide production and suppression of Kupffer
      cell activity and pro-inflammatory mediator and cytokines production.

PMID- 18816298
TI  - The effects of cannabidiol and tetrahydrocannabinol on motion-induced emesis in
      Suncus murinus.
AB  - The effect of cannabinoids on motion-induced emesis is unknown. The present study
      investigated the action of phytocannabinoids against motion-induced emesis in
      Suncus murinus. Suncus murinus were injected intraperitoneally with either
      cannabidiol (CBD) (0.5, 1, 2, 5, 10, 20 and 40 mg/kg), Delta(9)
      tetrahydrocannabinol (Delta(9)-THC; 0.5, 3, 5 and 10 mg/kg) or vehicle 45 min.
      before exposure to a 10-min. horizontal motion stimulus (amplitude 40 mm,
      frequency 1 Hz). In further investigations, the CB(1) receptor antagonist, N
      (piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3
      carboxamide (AM 251; 5 mg/kg), was injected 15 min. prior to an injection of
      Delta(9)-THC (3 mg/kg). The motion stimulus was applied 45 min. later. The number
      of emetic episodes and latency of onset to the first emetic episode were
      recorded. Pre-treatment with the above doses of CBD did not modify the emetic
      response to the motion stimulus as compared to the vehicle-treated controls.
      Application of the higher doses of Delta(9)-THC induced emesis in its own right,
      which was inhibited by AM 251. Furthermore, pre-treatment with Delta(9)-THC dose
      dependently attenuated motion-induced emesis, an effect that was inhibited by AM
      251. AM 251 neither induced an emetic response nor modified motion-induced
      emesis. The present study indicates that Delta(9)-THC, acting via the CB(1)
      receptors, is anti-emetic to motion, and that CBD has no effect on motion-induced
      emesis in Suncus murinus.

PMID- 18816299
TI  - In vitro inhibition of CYP1A2 by model inhibitors, anti-inflammatory analgesics
      and female sex steroids: predictability of in vivo interactions.
AB  - The cytochrome P450 enzyme CYP1A2 is crucial for the metabolism of many drugs,
      for example, tizanidine. As the effects of several non-steroidal anti
      inflammatory drugs (NSAID) and female sex steroids on CYP1A2 activity in vitro
      are unknown, their effects on phenacetin O-deethylation were studied and compared
      with the effects of model inhibitors in human liver microsomes, followed by
      prediction of their interaction potential with tizanidine in vivo. In vitro,
      fluvoxamine, tolfenamic acid, mefenamic acid and rofecoxib potently inhibited
      CYP1A2 [the 50% inhibitory concentration (IC(50)) < 10 microM].
      Ethinyloestradiol, celecoxib, desogestrel and zolmitriptan were moderate (IC(50)
      20-200 microM), and etodolac, ciprofloxacin, etoricoxib and gestodene weak
      inhibitors of CYP1A2 (IC(50) > 200 microM). At 100 microM, the other tested
      NSAIDs and steroids inhibited CYP1A2 less than 35%. Pre-incubation increased the
      inhibitory effects of rofecoxib, progesterone and desogestrel. Using the free
      portal plasma inhibitor concentration and the competitive inhibition model, the
      effect of fluvoxamine and the lack of effects of tolfenamic acid and celecoxib on
      tizanidine pharmacokinetics in human beings were well predicted. However, the
      effects of ciprofloxacin, rofecoxib and oral contraceptives were greatly
      underestimated even when the predictions were based on their total portal plasma
      concentration. Besides rofecoxib, and possibly mefenamic acid, other NSAIDs were
      predicted not to significantly inhibit CYP1A2 in human beings. The type of enzyme
      inhibition, particularly metabolism-dependent inhibition, free inhibitor
      concentration and accumulation of the inhibitor into the hepatocytes should be
      considered in extrapolations of in vitro results to human beings.

PMID- 18816300
TI  - Topiramate and vitamin e modulate antioxidant enzyme activities, nitric oxide and
      lipid peroxidation levels in pentylenetetrazol-induced nephrotoxicity in rats.
AB  - Previous studies have shown that generation of free radicals is increased
      following pentylenetetrazol kindling, due to increased cytosolic Ca2+
      concentrations. Topiramate, a voltage-gated calcium channel inhibitor, has an
      evident effect in the treatment of childhood epilepsy; however, topiramate may
      cause nephrotoxicity. We investigated the effects of topiramate and vitamin E
      administration on pentylenetetrazol-induced nephrotoxicity in rats by evaluation
      of lipid peroxidation, nitric oxide, glutathione peroxidase, catalase and
      superoxide dismutase values. Forty male Wistar rats were randomly divided into
      five equal groups. Group 1 was used as control and group II received a single
      dose of pentylenetetrazol. Fifty and 100 mg/kg topiramate daily were
      intragastrically administered to rats in groups III and IV for 7 days,
      respectively. Intragastric 100 mg topiramate (daily for 7 days) and
      intraperitoneal vitamin E (150 mg/kg, daily for 3 days) combination were given to
      animals in group V before a single-dose pentylenetetrazol administration. Serum
      and kidney samples were taken after 3 hr of pentylenetetrazol administration.
      Pentylenetetrazol resulted in a significant increase in nitric oxide levels of
      serum and kidney, and lipid peroxidation levels of kidney although superoxide
      dismutase and catalase activities in the kidney was reduced by pentylenetetrazol
      administration. The lipid peroxidation levels in serum and kidneys and the nitric
      oxide levels in kidneys of groups III, IV and V were decreased by topiramate
      although the superoxide dismutase and catalase activities in the kidneys were
      increased. Lipid peroxidation and nitric oxide levels were reduced by the
      topiramate and vitamin E combination compared to only topiramate. Glutathione
      peroxidase activity was not affect by pentylenetetrazol, topiramate and vitamin E
      administrations. In conclusion, topiramate and vitamin E have protective effects
      on pentylenetetrazol-induced nephrotoxicity by inhibition of free radicals and by
      support of the antioxidant redox system.

PMID- 18816301
TI  - Effects of short-term exposure to manganese on the adult rat brain antioxidant
      status and the activities of acetylcholinesterase, (Na,K)-ATPase and Mg-ATPase:
      modulation by L-cysteine.
AB  - Manganese (Mn) is an essential metalloenzyme component that in high doses can
      exert serious oxidative and neurotoxic effects. The aim of this study was to
      investigate the potential effect of the antioxidant L-cysteine (Cys, 7 mg/kg) on
      the adult rat brain total antioxidant status (TAS) and the activities of
      acetylcholinesterase (AChE), Na+,K+-ATPase and Mg2+-ATPase induced by short-term
      Mn administration (as Mn chloride, 50 mg/kg). Twenty-eight male Wistar rats were
      divided into four groups: A (saline-treated control), B (Mn), C (Cys) and D (Mn
      and Cys). All rats were treated once daily, for 1 week with intraperitoneal
      injections of the tested compounds. Rats were killed by decapitation and
      mentioned parameters were measured spectrophotometrically. Rats treated with Mn
      exhibited a significant reduction in brain TAS (-39%, P < 0.001, B versus A) that
      was partially reversed by Cys co-administration (-13%, P < 0.01, D versus A),
      while Cys (group C) had no effect on TAS. The rat brain AChE activity was found
      significantly increased by both Mn (+21%, P < 0.001, B versus A) and Cys (+61%, P
      < 0.001, C versus A), while it was adjusted into the control levels by the co
      administration of Mn and Cys. The activity of rat brain Na+,K+-ATPase was not
      affected by Mn administration, while Mg2+-ATPase exhibited a slight but
      statistically significant reduction in its activity (-9%, P < 0.01, B versus A)
      due to Mn, which was further reduced by Cys co-administration. The above findings
      suggest that short-term Mn in vivo administration causes a statistically
      significant decrease in the rat brain TAS and an increase in AChE activity. Both
      effects can be, partially or totally, reversed into the control levels by Cys co
      administration (which could thus be considered for future applications as a
      neuroprotective agent against chronic exposure to Mn and the treatment of
      manganism). The activity of Na+,K+-ATPase is not affected by Mn, while Mg2+
      ATPase activity is slightly (but significantly) inhibited by Mn, possibly due to
      Mg replacement.

PMID- 18816302
TI  - Disposition of a CYP2C9 phenotyping agent, losartan, is not influenced by the
      common 3435C > T variation of the drug transporter gene ABCB1 (MDR1).
AB  - Losartan is oxidized to E3174 by cytochrome P450 2C9 (CYP2C9); it has been
      suggested as a useful probe drug for CYP2C9 activity. It has also been shown to
      be a substrate for the drug-efflux transporter ATP-binding cassette sub-family B
      member 1 (ABCB1, MDR1). Both CYP2C9 and ABCB1 genes are polymorphic. The aim of
      the study was to determine if losartan disposition was influenced by the 3435C >
      T polymorphism of ABCB1 in healthy persons. These participants (n = 58) whose
      CYP2C9 genotypes and phenotypes were determined previously were genotyped for
      3435C > T polymorphism in ABCB1. The concentrations of losartan and E3174 were
      compared across genotypes for ABCB1 3435C > T variation. For persons with the
      ABCB1 3435 CC, CT, TT genotypes, the concentrations (microM, means +/- S.D.) of
      neither losartan (1.76 +/- 0.87, 1.68 +/- 0.84 and 1.80 +/- 0.85, respectively, P
      = 0.70) nor E3174 (2.97 +/- 2.49, 2.53 +/- 2.09 and 3.18 +/- 2.75, respectively,
      P = 0.65) were significantly different. These results suggest that ABCB1 3435C >
      T polymorphism does not have any influence on losartan disposition. Therefore,
      ABCB1 3435C > T polymorphism is probably not a confounding factor in the
      prediction of CYP2C9 activity by using losartan as a probe agent.

PMID- 18816303
TI  - Effects of subchronic versus acute in utero exposure to dexmedetomidine on foetal
      developments in rats.
AB  - Dexmedetomidine is a highly selective and specific alpha-2 adrenergic agonist
      with sedative, analgesic and sympathetic activities. This study was undertaken to
      investigate the effects of in utero exposure of dexmedetomidine on foetal
      development and postnatal behaviour in the offspring. Pregnant Sprague-Dawley
      rats were chronically treated with dexmedetomidine (0, 5, 10 and 20 microg/kg,
      subcutaneously) daily from gestation day 7 to day 19. Another group of animals
      received only a single acute dose of dexmedetomidine (20 microg/kg) on
      gestational day 19 to mimic a model for systemic analgesia during labour.
      Administration of dexmedetomidine did not affect the frequency of implantations.
      Chronic administration of 10 and 20 microg/kg of dexmedetomidine significantly
      reduced the body weight and crown-rump length of pups, whereas a single acute
      dose (20 microg/kg) did not affect these parameters. None of the pups exhibited
      any external malformations or skeletal abnormalities irrespective of treatment
      assigned. All the pups showed a normal postnatal weight gain during the
      developmental phase. No significant differences were observed among any of the
      groups with respect to behavioural performances of offspring in beam balance,
      grip strength and inclined plane tests as well as motor activity. In conclusion,
      acute exposure to dexmedetomidine at the anticipated delivery time does not exert
      any adverse effects on perinatal morphology of pups, their birth weight, crown
      rump length, physical growth and postnatal behavioural performances. Since this
      study was conducted in rats, its clinical relevance in human beings remains to be
      unclear and warrants further studies.

PMID- 18816304
TI  - Amelioration of cyclosporine A-induced renal, hepatic and cardiac damages by
      ellagic acid in rats.
AB  - Treatment with cyclosporine A has significantly improved long-term survival after
      organ transplantations. Cyclosporine A also causes a dose-related decrease in
      body functions in experimental animals and human beings. The generation of
      reactive oxygen species has been implicated in cyclosporine A-induced
      dysfunctions. The aim of this study was to determine the effects of ellagic acid
      on cyclosporine A-induced alterations in the kidney, liver and heart
      oxidant/antioxidant system. The control group was treated with placebo and
      subcutaneous injection of 0.5 ml isotonic saline + 0.5 ml slightly alkaline
      solution for 21 days. The cyclosporine A group received a subcutaneous injection
      of cyclosporine A (15 mg/kg) + 0.5 ml slightly alkaline solution for 21 days. The
      ellagic acid group was treated with a subcutaneous injection of 0.5 ml isotonic
      saline + ellagic acid (10 mg/kg) for 21 days. The cyclosporine A plus ellagic
      acid group received a subcutaneous injection of cyclosporine A + ellagic acid for
      21 days. Ellagic acid and slightly alkaline solution were administered by gavage.
      The rats were killed at the end of the treatment period. Malondialdehyde (MDA)
      and reduced glutathione (GSH) levels, glutathione peroxidase (GSH-Px) and
      catalase (CAT) activities were determined in kidney, liver and heart tissues.
      While administration of cyclosporine A increased the MDA levels in kidney, liver
      and heart tissues, it decreased the GSH, GSH-Px and CAT in these samples when
      compared to the control group. However, the simultaneously administration of
      ellagic acid markedly normalized the cyclosporine A-induced liver and heart MDA
      levels, liver CAT activities and GSH-Px activities of all samples. Cyclosporine A
      caused marked damages in the histopathological status of kidney, liver and heart
      tissues, which were partially ameliorated by ellagic acid administration. In
      conclusion, ellagic acid may be used in combination with cyclosporine A in
      transplantation treatment to improve the cyclosporine A-induced oxidative stress
      parameters and other adverse effects.

PMID- 18816305
TI  - Serious anaphylactic reactions due to protamine sulfate: a systematic literature
      review.
AB  - Anaphylactic reactions caused by injection of protamine sulfate during cardiac
      surgery are a well-known complication. A systematic literature review was
      therefore conducted to gather evidence of the knowledge concerning these side
      effects, and to see if any prospective randomized studies supported this. Studies
      investigating the effect of protamine sulfate in human beings were extracted from
      MEDLINE, Embase and the Cochrane Library, retrieving 487 articles. Abstracts were
      evaluated by both authors, and referred articles not found in the primary search
      were furthermore extracted from reviews and case reports, resulting in a total of
      272 relevant articles. Of these, 9 retrospective studies and 16 prospective
      studies were performed in an evidence-based manner. However, only 3 of the 16
      prospective articles had an optimal design as far as inclusion criteria,
      randomization, and description of symptoms were concerned. Incidence of
      anaphylactic reactions in the prospective studies was 0.69% compared to 0.19% in
      the retrospective studies, but caution should be taken due to a pronounced
      heterogeneity of those studies. One study found heparinase I unsuitable as
      replacement for protamine sulfate. Overall, our findings support the low
      incidence of anaphylactic reactions reported in previous studies, but of note
      only few prospective investigations was conducted on the subject. Our study also
      emphasizes the need for critical appraisal of many routine procedures: in all
      aspects of medical care, systematic literature review conducted in a well
      structured, repeated manner should be given high priority.

PMID- 18816306
TI  - Improving organ donation rates - what can be done?

PMID- 18816307
TI  - Care to remember? Why it's just common sense.

PMID- 18816308
TI  - Asymmetry in the intensive care unit: redressing imbalance and meeting the needs
      of family.
AB  - AIMS AND OBJECTIVES: The purpose of this study was to develop a way for nurses to
      understand how they negotiate and work with families in the intensive care unit
      (ICU). BACKGROUND: The importance of family to the critically ill patient is
      described in previous research; however, research exploring how to work with
      families in the clinical context of ICU is modest and there is little information
      and research to understand how the nurse might work to integrate family and
      understand family needs in the clinical context. DESIGN: The study was designed
      using action research methodology where an action research group of registered
      nurses from ICU proposed changes to how the family are defined, assessed and
      understood. METHODS: In the action research group and reflective conversations,
      the group planned new assessment tools to use in ICU to work with the family.
      RESULTS: Exploring their pragmatic knowledge of the context, the action research
      group suggested ways of working with families that did not impede the clinical
      work of the ICU. Families provided information about themselves and the patient
      that helped the nurse to plan care that redressed some of the asymmetrical nature
      of the relationship in the ICU. CONCLUSIONS: This research created novel ways of
      viewing family and offers strategies to address asymmetry between families and
      ICU professionals. RELEVANCE TO CLINICAL PRACTICE: Positive steps to redress
      asymmetrical relationships can help ensure that family care is better integrated
      into ICU practice.

PMID- 18816309
TI  - Endotracheal suctioning in children with severe traumatic brain injury: a
      literature review.
AB  - AIM: This paper aims to present an overview of the literature relating to the
      effects of endotracheal suctioning (ETS) in children and adults with severe
      traumatic brain injury (TBI). BACKGROUND: TBI is the leading cause of death in
      children worldwide and continues to result in widespread mortality and morbidity.
      In intensive care, ETS is an essential nursing procedure that is undertaken but
      is known to produce some adverse effects in children. METHOD: A comprehensive
      literature search was undertaken using a Parahoo and quality of reporting of meta
      analyses (QUOROM) approach. A range of databases was searched to identify
      published papers with key search terms. The databases searched included Cochrane
      Library, Medline, PubMed Central, CINAHL, Proquest and Science Direct. FINDINGS:
      This review is based on 21 papers (with 433 patients in total), but specific
      papers in paediatric head injury children were extremely limited, and the
      evidence was largely dated and inconclusive. Although the majority of papers
      demonstrate an increase in intracranial pressure (ICP) with ETS, there are
      contradictory results with regard to recovery times. CONCLUSIONS: Further
      research is needed specifically into the effect of ETS on ICP and cerebral
      perfusion pressure of children with severe TBI, taking into account all the known
      confounding variables.

PMID- 18816310
TI  - Ventilator-associated pneumonia in paediatric intensive care: a literature
      review.
AB  - BACKGROUND: Ventilator-associated pneumonia (VAP) has been identified as the most
      common nosocomial infection in intensive care units (ICUs) with associated health
      and financial costs. To date, more research has been carried out in adult ICUs
      than in paediatric units, thus prompting a review and investigation of the
      implications for paediatric practice. AIMS: To identify relevant paediatric
      literature surrounding VAP and use this in association with research carried out
      in the adult environment to establish the implications of VAP and possible
      management strategies. SEARCH STRATEGIES: A literature search was undertaken
      using databases within DialogDatastar to identify the extent to which VAP has
      been researched in both paediatric and adult centres. This information was used
      to try and gain a clearer concept of the impact and management of VAP in the
      paediatric setting. Key words and combinations included VAP, intensive care,
      paediatric, antibiotics, positioning, suction, economics, management, nosocomial
      and morbidity and mortality. RESULTS OF ANALYSIS: Despite the documented
      significance of VAP in terms of its financial and health implications,
      discrepancies and inconsistencies exist surrounding the identification and
      treatment of VAP. This is reflected in paediatric centres by a dearth of
      literature on the subject and the lack of a national standard as to the
      management and prevention of VAP. Inappropriate management of VAP plays an
      important role in the development and spread of multiresistant bacteria within
      hospitals. CONCLUSIONS: While inadequate paediatric research exists,
      extrapolating from adult research suggests that the financial and health costs of
      VAP are substantial and can be reduced by introducing simple low-cost measures.
      Such measures include improving education surrounding VAP and its implications
      and making small changes in practice to improve and maintain oral hygiene
      standards. IMPLICATIONS: With a growing cohort of paediatric patients requiring
      short- and long-term ventilation, progress must be made in identifying the extent
      and impact of VAP in paediatric ICUs and among the community ventilated patients.
      This will require changes in practice and attitudes towards VAP for which an
      appropriate knowledge base would need to be established using audit and research.
      These issues are particularly relevant in the current environment given the links
      with multiresistant strains of bacteria within hospitals and the community.

PMID- 18816311
TI  - Multiple organ dysfunction syndrome pathogenesis and care: a complex systems'
      theory perspective.
AB  - AIMS AND OBJECTIVES: To discuss multiple organ dysfunction syndrome (MODS) from a
      complex systems' theory perspective and to delineate a conceptual framework for
      the development and care of MODS. BACKGROUND: MODS is an intricate and
      devastating manifestation of critical illness characterized by widespread
      aberrant molecular, cellular and systemic responses. DESIGN AND METHODS:
      Narrative literature review (MEDLINE, CINAHL databases) and knowledge synthesis
      with the theoretical assertions of chaos and complex systems' theory. Cellular
      and systemic response paradoxes in MODS (including cellular hypoxia, cell death
      and signalling) are reviewed. RESULTS: The diseased person is depicted as a
      complex adaptive system. The relevancy of some of the principles of complex
      chaotic systems' theory to the proposed model is illustrated, including sensitive
      dependence on initial conditions, emergence, attractors, self-organization, self
      organized criticality and emerging order. The transition from life-supporting to
      death-related organismic responses is illustrated as a critical event in MODS and
      care implications are drawn. CONCLUSIONS: Patient responses in MODS appear to
      conform to the principles of chaotic systems. Death is illustrated not as a
      consequence of homeostatic failure but as a 'deliberate' self-organized
      phenomenon entailing multiple dynamically evolving mechanisms. RELEVANCE TO
      CLINICAL PRACTICE: Some of the principles of chaotic complex systems may need to
      be taken into account to advance care in MODS. An alternative theoretical
      perspective may support nurses to conceptualize both MODS and their role in a way
      that will help them to cope better with this devastating syndrome and develop
      practice.

PMID- 18816312
TI  - The LoTrach system: its role in the prevention of ventilator-associated
      pneumonia.
AB  - OBJECTIVES: To discuss the development of the LoTrach system in light of current
      evidence around the prevention of ventilator-associated pneumonia (VAP) and its
      practical application in the intensive care setting. BACKGROUND: VAP causes
      substantial morbidity and mortality in ventilated patients in the Intensive Care
      Unit (ICU), increases length of stay in ICU and is extremely costly. Strategies
      are needed to reduce the risk of VAP. METHOD: We examine the need for an
      endotracheal tube (ETT) specifically designed for the critically-ill patient, the
      development of the LoTrach system from conception to production, and the role of
      the various components of the system in preventing VAP. Early issues in
      implementing this revolutionary equipment into ICU are explored and three case
      studies highlight advantages of this system. CONCLUSION: The LoTrach system has
      been designed to facilitate the provision of a number of evidence-based
      interventions that have been shown to reduce VAP. Pulmonary aspiration is
      ubiquitous with conventional cuffs but prevented by the cuff of the LoTrach
      system when held at a constant and safe pressure against the tracheal wall with a
      cuff pressure controller. Other aspects incorporated in the ETT are aimed at
      clearing the secretions from the subglottic space, preventing tube occlusion and
      accidental extubation, and avoiding damage to the airway. In this way the LoTrach
      system employs a multifactorial approach to the prevention of VAP and the cost
      savings from LoTrach rather than a standard ETT will be considerable because of
      an average 3 day reduction in ICU length of stay related to this. It thus has the
      potential to be a very useful tool in the ICU setting in the prevention of VAP.

PMID- 18816313
TI  - Mentoring in times of change.
AB  - OBJECTIVE: The aim of this study was to establish the barriers to nurses
      performing the mentor role in three critical care wards. BACKGROUND: Imminent
      changes affecting mentors to preregistration students in our wards and our
      awareness of their ill-preparedness prompted us to design interventions to
      prepare colleagues for the changes. Literature shows a range of perceived
      barriers to mentoring, we wanted to compare these to our colleagues' perceptions
      DESIGN: Prospective, self-administered service evaluation questionnaire of a
      saturation sample of nurses in intensive care and high dependency wards. RESULTS:
      Of the 118 questionnaire proformas issued, 43 were returned (36%). Key results
      include: lack of time to perform the mentor role because of patient care
      workload, lack of opportunity to update knowledge and skills of mentoring and
      lack of familiarity with the programme of study and the documents used to record
      assessment of a student's proficiency. CONCLUSIONS: Mentor update opportunities
      must be delivered alongside the competing demands of safe and effective patient
      care and the need to ensure the development of individuals as well as the
      profession as a whole through fostering its students. RELEVANCE TO PRACTICE: To
      ensure future generations of patients enjoy quality critical care, we must invest
      time and resources in mentoring the nurses who will deliver critical care in the
      future.

PMID- 18816314
TI  - Commentary: Hugonnet S et al. (2007). The effect of workload on infection risk in
      critically ill patients.

PMID- 18816315
TI  - A case study of severe malaria: implications for practice.

PMID- 18816317
TI  - Supporting participation in clinical research: decision aids for trial
      recruitment?

PMID- 18816318
TI  - When doctors disagree: a qualitative study of doctors' and parents' views on the
      risks of childhood food allergy.
AB  - OBJECTIVE: To examine the views of doctors which underpin clinical practice
      variation concerning an uncertain health risk, and the views of parents who had
      sought advice from these doctors, using the example of childhood food allergy.
      STUDY DESIGN: Qualitative study involving in-depth interviews and participant
      observation over 16 months. Focus groups and consultation audio-recordings
      provided corroborative data. SETTING: Three specialist allergy clinics located in
      one metropolitan area. PARTICIPANTS: Eighteen medical specialists and trainees in
      allergy, and 85 parents (from 69 families) with food allergic children. RESULTS:
      Doctors expressed a spectrum of views. The most divergent views were
      characterized by: scientific scepticism rather than precaution in response to
      uncertainty; emphasis on quantifiable physical evidence rather than parental
      histories; professional roles as providers of physical diagnosis and treatment
      rather than of information and advocacy; libertarian rather than communitarian
      perspectives on responsibility for risk; and values about allergy as a disease
      and normal childhood. Parents held a similar, but less divergent range of views.
      The majority of parents preferred more moderate doctors' views, with 43% (30 of
      69) of families expressing their dissatisfaction by seeking another specialist
      opinion. Many were confused by variation in doctors' opinions, preferring
      relationships with doctors that recognized their concerns, addressed their
      information needs, and confirmed that they were managing their child's allergy
      appropriately. CONCLUSIONS: In uncertain clinical situations, parents do not
      expect absolute certainty from doctors; inflexible certainty may not allow
      parental preferences to be acknowledged or accommodated, and is associated with
      the seeking of second opinions.

PMID- 18816319
TI  - BRCA mutation-negative women from hereditary breast and ovarian cancer families:
      a qualitative study of the BRCA-negative experience.
AB  - BACKGROUND: When women from families with a known BRCA1 or BRCA2 mutation test
      negative for the family mutation, it is assumed that they will transition their
      personal cancer risk perception from high to average risk. However, there are
      scant data regarding the experience of mutation-negative women after genetic
      testing disclosure, particularly related to the shift of risk perception from
      assumed mutation-positive to actual mutation-negative. This study was designed to
      explore cancer risk perception and the experience of being a mutation-negative
      woman within a known BRCA1/2 mutation-positive family. METHODS: We employed a
      qualitative descriptive design and convened a sample of 13 women who contributed
      in-depth, semi-structured telephone interviews (audio-recorded and transcribed
      verbatim) and performed qualitative content analysis with NVivo 2.0 software.
      RESULTS: Six major content areas emerged from interview data: (i) rationale for
      initial involvement in the breast imaging study, (ii) rationale for continued
      participation, (iii) experience of living in a multiple-case family, (iv) risk
      perception: the personal meaning of mutation-negative status, (v) opinions
      regarding cancer aetiology and (vi) communication patterns between mutation
      negative and mutation-positive family members. CONCLUSIONS: Living in a
      hereditary breast and ovarian cancer family is a complex experience that affects
      cognitive, emotional and social functioning. Our findings indicate that mutation
      negative women may have unmet psychosocial needs that must be addressed by health
      care professionals, particularly in the primary-care setting following genetic
      disclosure of a potentially reassuring result regarding their lack of the very
      high cancer risks associated with BRCA1/2 mutations.

PMID- 18816321
TI  - Improving informed consent: pilot of a decision aid for women invited to
      participate in a breast cancer prevention trial (IBIS-II DCIS).
AB  - BACKGROUND: Patients and clinicians report difficulties with the process of
      informed consent to clinical trials and audiotape audits show that critical
      information is often omitted or poorly presented. Decision aids (DAs) may assist
      in improving consent. AIMS: This study piloted a DA booklet for a high priority
      breast cancer prevention trial, IBIS-II DCIS, which compares the efficacy of an
      aromatase inhibitor (anastrozole) with tamoxifen in women who have had surgery
      for ductal carcinoma in situ (DCIS). METHOD: Thirty-one Australian women
      participating in the IBIS-I breast cancer prevention trial and who are currently
      in follow-up agreed to read the IBIS-II DCIS participant information sheet and
      the DCIS DA booklet, complete a set of standardized questionnaires, and provide
      feedback on the DA via a semi-structured phone interview. RESULTS: Women found
      the DA helpful in deciding about trial participation, reporting that it aided
      their understanding over and above the approved IBIS-II DCIS participant
      information sheet and was not anxiety provoking. Women's understanding of the
      rationale and methods of clinical trials and the IBIS-II DCIS trial was very
      good; with more than 80% of items answered correctly. The only areas that were
      not understood well were the concepts of randomization and blinding. CONCLUSIONS:
      This study suggests that the DA will be acceptable to and valued by potential
      participants in the IBIS-II DCIS study. The revised DA is currently being
      evaluated prospectively in a randomized controlled trial. If successful, such DAs
      could transform the consent process to large clinical trials and may also reduce
      dropout rates.

PMID- 18816320
TI  - A systematic review of decision support needs of parents making child health
      decisions.
AB  - OBJECTIVE: To identify the decision support needs of parents attempting to make
      an informed health decision on behalf of a child. CONTEXT: The first step towards
      implementing patient decision support is to assess patients' information and
      decision-making needs. SEARCH STRATEGY: A systematic search of key bibliographic
      databases for decision support studies was performed in 2005. Reference lists of
      relevant review articles and key authors were searched. Three relevant journals
      were hand searched. INCLUSION CRITERIA: Non-intervention studies containing data
      on decision support needs of parents making child health decisions. DATA
      EXTRACTION AND SYNTHESIS: Data were extracted on study characteristics, decision
      focus and decision support needs. Studies were quality assessed using a pre
      defined set of criteria. Data synthesis used the UK Evidence for Policy and
      Practice Information and Co-ordinating Centre approach. MAIN RESULTS: One-hundred
      and forty nine studies were included across various child health decisions,
      settings and study designs. Thematic analysis of decision support needs indicated
      three key issues: (i) information (including suggestions about the content,
      delivery, source, timing); (ii) talking to others (including concerns about
      pressure from others); and (iii) feeling a sense of control over the process that
      could be influenced by emotionally charged decisions, the consultation process,
      and structural or service barriers. These were consistent across decision type,
      study design and whether or not the study focused on informed decision making.

PMID- 18816322
TI  - Considering patient non-participation in health care.
AB  - OBJECTIVE: The aim of this study was to depict patient non-participation as
      described by a diverse group with recent experiences of being patients.
      BACKGROUND: Patient participation is regarded as a primary condition for optimal
      quality of care, suggesting that non-participation should be avoided. A common
      understanding of the concept of patient non-participation is needed. A
      discrepancy in definitions of patient non-participation has been found in health
      care interactions, health-care classifications and health-care research, and
      little is known of what patient non-participation represents to patients. STUDY
      DESIGN: A survey consisting of closed-ended and open-ended questions was
      administered to persons that had recently been patients to gather respondents'
      descriptions of what they considered as patient non-participation. Qualitative
      content analysis was used to analyse free-text descriptions, and descriptive
      statistics were used for the close-ended alternatives. FINDINGS: Lacking
      information (e.g. not being provided with appropriate information) and lacking
      recognition (e.g. not being listened to and/or lacking recognition as an
      individual with individual needs and concerns) were significant aspects of
      patient non-participation. Furthermore, non-participation encompassed facing
      organization-centred, as opposed to patient-centred, health care as well as
      feeling insecure in health care interactions. CONCLUSION: The findings provide
      input for a better understanding of what patients experience as non
      participation. Organising for the caregivers to be able to thoroughly listen to
      the patients' illness narratives would easily reduce the risk of patient's
      experiencing what is described as non-participation and would provide a sound
      base for patient learning needs.

PMID- 18816323
TI  - Citizens' juries in planning research priorities: process, engagement and
      outcome.
AB  - BACKGROUND: Involving members of the public in setting priorities for health
      research in becoming increasingly common practice. One method used in public
      involvement exercises is the citizens' jury. OBJECTIVE: This article examines
      some challenges and benefits of citizens' juries, including issues relating to
      process, public engagement and outcome. DESIGN: In Bristol, UK, a citizens' jury
      was held with the aim of identifying local priorities for research into health
      and social care. This jury is used as an example through which key issues in
      public involvement and jury processes are explored. SETTING AND PARTICIPANTS: The
      Bristol Citizens' Jury comprised 20 members of the public ('jurors'), an
      oversight panel and a steering group. The jurors met at 11 consecutive sessions
      during 2006 over a period of 16 weeks, which culminated in a written report. All
      the sessions were audio-recorded, five sessions were observed and video-recorded,
      and 16 jurors completed written feedback forms at the end of the jury process.
      FINDINGS AND CONCLUSION: In this article we discuss degree and timing of public
      involvement in the process of health research; the role of context;
      representation of communities; processes of deliberation and knowledge
      production; and how constraints of time and cost may affect public involvement.
      It was clear that jurors who took part in the Bristol Citizens' Jury were engaged
      and committed. This engagement may be related to jurors' belief in their ability
      to shape future research alongside concern about the relevance of the issues
      under discussion. Opposing emotions of tension and harmony are a crucial part of
      the deliberation process.

PMID- 18816324
TI  - Engaging the public in priority-setting for health technology assessment:
      findings from a citizens' jury.
AB  - OBJECTIVES: To assess the feasibility of using a citizens' jury to elicit public
      values on health technologies and to develop criteria for setting priorities for
      health technology assessment (HTA). METHODS: Sixteen individuals were selected
      from 1600 randomly sampled residents of the Capital Health Region in Alberta,
      Canada. They participated in a 2 (1/2) day jury which comprised presentations by
      'expert witnesses', who represented innovators, patients, health-care policy
      makers and clinicians, as well as a series of small and large group priority
      setting exercises based on actual examples of technologies that had recently been
      considered for assessment by local and national HTA bodies. The session was audio
      taped, and transcripts were independently reviewed by two researchers using
      content analytical techniques in order to ensure that no important concepts
      expressed by individual jurors were missed during group development of the final
      list of priority-setting criteria. Jurors evaluated the process by completing
      self-administered, semi-structured questionnaires at the end of the session.
      Responses were analysed using qualitative methods. RESULTS: The jury identified
      13 criteria, which they subsequently ranked in order of importance. The top two
      criteria included 'potential to benefit a number of people' and 'extends life
      with quality'. Based on feedback from questionnaires, jurors valued the
      opportunity to become engaged in such a process, and expressed interest in
      participating in future juries. CONCLUSIONS: Citizens' juries offer a feasible
      approach to involving the public in priority-setting for HTA. Furthermore,
      technologies that may benefit a number of people and improve quality of life
      appear to be of greatest importance to the public.

PMID- 18816325
TI  - Hospital inpatients' experiences of access to food: a qualitative interview and
      observational study.
AB  - BACKGROUND: Hospital surveys indicate that overall patients are satisfied with
      hospital food. However undernutrition is common and associated with a number of
      negative clinical outcomes. There is little information regarding food access
      from the patients' perspective. PURPOSE: To examine in-patients' experiences of
      access to food in hospitals. METHODS: Qualitative semi-structured interviews with
      48 patients from eight acute wards in two London teaching hospitals. Responses
      were coded and analysed thematically using NVivo. RESULTS: Most patients were
      satisfied with the quality of the meals, which met their expectations. Almost
      half of the patients reported feeling hungry during their stay and identified a
      variety of difficulties in accessing food. These were categorized as:
      organizational barriers (e.g. unsuitable serving times, menus not enabling
      informed decision about what food met their needs, inflexible ordering systems);
      physical barriers (not in a comfortable position to eat, food out of reach,
      utensils or packaging presenting difficulties for eating); and environmental
      factors (e.g. staff interrupting during mealtimes, disruptive and noisy behaviour
      of other patients, repetitive sounds or unpleasant smells). Surgical and elderly
      patients and those with physical disabilities experienced greatest difficulty
      accessing food, whereas younger patients were more concerned about choice, timing
      and the delivery of food. CONCLUSIONS: Hospital in-patients often experienced
      feeling hungry and having difficulty accessing food. These problems generally
      remain hidden because staff fail to notice and because patients are reluctant to
      request assistance.

PMID- 18816328
TI  - A look at the significance of the AAPM-AMA relationship.

PMID- 18816326
TI  - Patient Advice and Liaison Services: results of an audit survey in England.
AB  - OBJECTIVE: To assess the extent national standards for Patient Advice and Liaison
      Services (PALS) were achieved across England. CONTEXT: PALS are an important
      element of patient and public involvement strategy in England. Seven national
      standards for PALS were identified. Previous research has not assessed PALS
      across all trust types in England. DESIGN: Audit survey as part of a mixed method
      'realistic evaluation' in which regularities of context, mechanism and outcome
      are hypothesized and tested. SETTING AND PARTICIPANTS: PALS based in 570 NHS
      trusts in England between October and December 2005. MAIN OUTCOME MEASURES: Self
      reported achievement against PALS national standards. RESULTS: Three hundred and
      thirty-six valid responses were received, a response rate of 65%. However because
      some PALS serve more than one trust, this represents an estimated 76% of trusts.
      Overall, PALS rated themselves highly against all the standards, though somewhat
      less highly against standard 2 (seamlessness across health and social care) and
      standard 6 (acting as a catalyst for culture change). There was a wide range of
      responses with regard to PALS budget, staffing and activity levels, and
      statistically significant associations between levels of funding and staffing and
      higher levels of performance. CONCLUSIONS: The overall response rate was good so
      there can be a high degree of confidence in the reliability of the results. The
      results indicate the challenging context in which PALS are operating. Although
      the majority of PALS are single trust PALS, there is a high degree of variation
      in key mechanism factors such as budget and staffing.

PMID- 18816329
TI  - Pain and addiction interface.

PMID- 18816330
TI  - The self-administered 24-item geriatric pain measure (GPM-24-SA): psychometric
      properties in three European populations of community-dwelling older adults.
AB  - OBJECTIVE: To explore the feasibility and psychometric properties of a self
      administered version of the 24-item Geriatric Pain Measure (GPM-24-SA). DESIGN:
      Secondary analysis of baseline data from the Prevention in Older People
      Assessment in Generalists' practices trial, an international multi-center study
      of a health-risk appraisal system. PARTICIPANTS: One thousand seventy-two
      community dwelling nondisabled older adults self-reporting pain from London, UK;
      Hamburg, Germany; and Solothurn, Switzerland. OUTCOME MEASURES: GPM-24-SA as part
      of a multidimensional Health Risk Appraisal Questionnaire including self-reported
      demographic and health-related information. RESULTS: Among the 1,072 subjects,
      655 had complete GPM-24-SA data, 404 had <or=30% missing GPM-24-SA data, and 13
      had >30% missing GPM-24-SA data. In psychometric analyses across the three
      European populations with complete GPM-24-SA data, the measure exhibited stable
      internal consistency, good convergent, divergent and discriminant validity, and
      produced stable pain measurements. However, factor analysis indicated differences
      in the GPM-24-SA across sites with discrepancies mainly related to items of a
      single subscale that failed to load appropriately. Analyses including imputation
      for subjects with <or=30% missing data demonstrated psychometric properties
      comparable to complete data analyses suggesting that imputation in cases with
      <or=30% missing GPM-24-SA data provides sufficient information to generate a
      valid score. CONCLUSION: The GPM-24-SA is a promising tool for self-administered
      assessment of pain in community dwelling older adults. However, because of
      incomplete response and uncertainty in factor structure, further refinement and
      psychometric evaluation of the GPM-24-SA is needed before it could be recommended
      for widespread use.

PMID- 18816331
TI  - Source of drugs for prescription opioid analgesic abusers: a role for the
      Internet?
AB  - OBJECTIVE: There has been a sharp increase in the abuse of prescription opioid
      analgesics in the United States in the past decade. It has been asserted,
      particularly by several governmental and regulatory agencies, that the Internet
      has become a significant source of these drugs which may account to a great
      extent for the surge in abuse. We have studied whether this is correct. DESIGN:
      We asked 1,116 prescription drug abusers admitted for treatment, through
      standardized questionnaires, where they obtained their drugs. We also attempted
      to purchase scheduled II and III drugs from a random sample of Internet sites
      offering such sales. RESULTS: Dealers, friends or relatives, and doctors'
      prescriptions were listed as a source of drugs with equal frequency (
      approximately 50-65%), with theft and forgery far behind at 20%. The Internet was
      mentioned by fewer than 6% of the total responders. Because these data suggest
      either lack of availability or that our sample has not yet realized that the
      Internet is a potential source, we attempted to purchase scheduled II and III
      opioids and the unscheduled opioid, tramadol, from a random sample of 10% of the
      sites listing such sales. We were unsuccessful in purchasing a single scheduled
      opioid analgesic, but found that tramadol, as an unscheduled drug, was freely
      available. CONCLUSIONS: The assertion that the Internet has become a dangerous
      new avenue for the diversion of scheduled prescription opioid analgesics appears
      to be based on no empirical evidence and is largely incorrect.

PMID- 18816333
TI  - Assessing legal risk.

PMID- 18816332
TI  - Improved opioid analgesic effect following opioid dose reduction.
AB  - INTRODUCTION: Traditionally, opioids have been the cornerstone of therapy for
      patients suffering from cancer pain, regardless of the potential to develop
      opioid tolerance. In chronic pain patients who experience worsening pain despite
      increasing doses of opioids, the clinical role of opioid-induced hyperalgesia is
      gaining more recognition. CASE: Presented here is the case of a 56-year-old man
      with recurrent squamous cell lung carcinoma and spinal metastases, suffering with
      intractable 8/10 pain on the visual analog scale in his chest, lower thoracic
      spine, and upper lumbar spine. He was admitted five times for pain control. In
      spite of escalating doses of oxycodone, morphine, and hydromorphone, the patient
      continued to experience severe pain. Also, he endured undesirable sedation,
      fatigue, and generalized weakness. The clinical picture suggested the possibility
      of opioid-induced hyperalgesia. We decreased the hydromorphone dose by 40-50% and
      started methadone. The patient's pain level dropped to a more acceptable 3/10. He
      was more alert, and his pain was tolerable until his death. DISCUSSION: Opioid
      induced hyperalgesia might be considered in a patient who has no evidence of
      disease progression, who is on clinically reasonable doses of opioids, and whose
      pain escalates as opioid doses are increased. A reduction of opioids and the
      addition of a low-dose N-methyl-D-aspartate receptor antagonist may provide a
      favorable clinical outcome in those patients who have failed to benefit from
      opioid rotation and other adjunctive pain treatments.

PMID- 18816334
TI  - Pain and the courtroom--paving the way for a long-overdue showdown.

PMID- 18816337
TI  - The logic of turmoil: some epistemological and clinical considerations on
      emotional experience and the infinite.
AB  - The idea of the infinite has its origins in the very beginnings of western
      philosophy and was developed significantly by modern philosophers such as Galileo
      and Leibniz. Freud discovered the Unconscious which does not respect the laws of
      classical logic, flouting its fundamental principle of non-contradiction. This
      opened the way to a new epistemology in which classical logic coexists with an
      aberrant logic of infinite affects. Matte Blanco reorganized this Freudian
      revolution in logic and introduced the concept of bi-logic, which is an
      intermingling of symmetric and Aristotelic logics. The authors explore some
      epistemological and clinical aspects of the functioning of the deep unconscious
      where the emergence of infinity threatens to overwhelm the containing function of
      thought, connecting this topic to some of Bion's propositions. They then suggest
      that bodily experiences can be considered a prime source of the logic of turmoil,
      and link a psychoanalytic consideration of the infinite to the mind-body
      relation. Emotional catastrophe is seen both as a defect-a breakdown of the
      unfolding function which translates unconscious material into conscious
      experience-and as the consequence of affective bodily pressures. These pressures
      function in turn as symmetrizing or infinitizing operators. Two clinical
      vignettes are presented to exemplify the hypotheses.

PMID- 18816338
TI  - 'Don't save her'- Sigmund Freud meets Project Pat: the rescue motif in hip-hop.
AB  - Freud originally explicated the dynamics of rescue wishes by describing men who
      fell in love with prostitutes. He saw this attempt at attachment as driven by the
      man's wish to repay his parents for giving him life. Many subsequent writers
      shift this emphasis, seeing rescue wishes as motivated by aggressive oedipal
      competition with the father. This article highlights the attachment aspects of
      Freud's original conception and traces how writers in the last three decades use
      the family romance rather than Oedipus as a model to view rescue wishes as having
      a more tender aspect. Rescue wishes are especially characteristic of the
      developmental stage of young adulthood. They at once attempt to repay the
      parental debt the young adult feels and serve as practice for the vicissitudes of
      the couple bond and the benign sacrifices of parenthood. Popular culture contains
      many vivid examples of Freud 's original description of the rescue-motif. A
      detailed examination of the rap song, Don't save her, demonstrates all the
      elements of Freud's original conception and the interpersonal risks of the rescue
      relationship. Three additional rap songs by other artists are briefly analyzed to
      show the extensive occurrence of the wish to rescue and its psychic and
      interpersonal dangers.

PMID- 18816339
TI  - Grievance: the underlying oedipal configuration.
AB  - In this paper the author describes some of the clinical features encountered in
      patients who seem to 'nurture' a persistent grievance. He gives clinical
      examples, and discusses the nature of the powerful underlying dynamics. He
      suggests that contained within the patient's grievance is a set of phantasies
      that constitute the expression of his fear and hatred of reality, particularly
      the reality of the oedipal situation, the child's relationship to the creative
      parental couple, which Money-Kyrle (1968, 1971) has characterised as an essential
      element of 'the facts of life'. The phantasies the patient has evolved serve to
      protect him from envy and jealousy, anxiety and guilt. The primitive oedipal
      phantasies on which the grievance rests also contribute to the excitement and
      gratification that are characteristic of the grievance. The analysis of the
      underlying state of mind helps to account for the persistent grip the grievance
      has on the patient, and the way this interferes with development.

PMID- 18816340
TI  - Transference symptom.
AB  - Transference symptom is a hazy notion in Freud's writings. The notion is
      presented here as a particular moment in the crystallization of the transference
      neurosis. It results from a double cathexis of the analytic frame and the analyst
      resulting in a symbolic distortion that is represented plastically within the
      session, as occurs in dreams. The transference symptom proceeds from two
      different preconscious cathexes, one attached to the reality of the frame, the
      other to the drive linked to the analyst. A psychic space is thereby opened up
      for interpreting both the resistance and the unconscious derivatives of infantile
      conflict. The transference symptom is a compromise formation that includes the
      analyst and questions the countertransference stance. Three different analytic
      situations give rise to transference symptoms according to the relative balance
      between frame and process in the analytic encounter. The concept is compared with
      enactment.

PMID- 18816341
TI  - Introduction to the paper by Madeleine and Willy Baranger: the analytic situation
      as a dynamic field.

PMID- 18816342
TI  - Some notes on the English translation of The analytic situation as a dynamic
      field by Willy and Madeleine Baranger.

PMID- 18816343
TI  - The analytic situation as a dynamic field. 1969.

PMID- 18816344
TI  - From Psychical treatment to psychoanalysis: considerations on the misdating of an
      early Freud text and on a hitherto overlooked addition to it (here reproduced).
AB  - Freud's early paper Psychical (or mental) treatment, first published in a family
      reference book for educated lay persons, was reproduced in the Gesammelte Werke
      with a stated publication date of 1905. This date was subsequently called into
      question owing to certain parts of the subject-matter (the use of hypnosis and
      suggestion in 'mental treatment'), and the contribution was erroneously assigned,
      for instance by James Strachey, to the year 1890. This error is corrected in the
      present paper. Furthermore, the existence of a second edition of this reference
      book, which contains an addition to Freud's text and appeared in 1918-19, has
      previously gone unnoticed. The first edition had been published in 1905-6.
      Freud's contribution must, however, have been written at an appreciably earlier
      date. The probable time of its genesis is discussed. Freud's new text is
      reproduced (in English translation) for the first time in an appendix to this
      paper.

PMID- 18816345
TI  - From psychosocial equilibrium to catastrophic breakdown: Cyprus 1955-1974.
AB  - The recent history of Cyprus presents an example of a society in which a
      centuries-long peaceful coexistence of diverse populations gave way to violence
      and murderous hate, with devastating end results. This paper tries to understand
      and describe the process by which Cypriot society slid from a position of
      psychosocial equilibrium and integration towards one of disintegration,
      fragmentation and catastrophic breakdown. This paper draws from work by social
      anthropologists, sociologists, historians and others, and from my own personal
      experience. To these I applied insights afforded by psychoanalysis to identify
      and explore the psychic processes and states of mind that characterized a
      psychosocial disintegrative process. I came to see external political events and
      internal psychological processes as inseparably intertwined and dynamically
      interdependent, each emanating from and catalysing the other. The factual details
      of the process described are of course unique in their local specificity, but the
      psychic phenomena that characterized it are not: at both the individual and group
      levels they are replicated in other societies undergoing similar processes of
      self-destruction.

PMID- 18816354
TI  - Disparity and responsibility.

PMID- 18816355
TI  - In response to the published article "Application of the community readiness
      model for childhood obesity prevention (Findholt, 2007)".

PMID- 18816356
TI  - Risk factors for low birth weight infants of Hispanic, African American, and
      White women in Bexar County, Texas.
AB  - OBJECTIVES: The aim of this study was to compare the risk factors in women who
      delivered an infant of low birth weight (LBW, <2,500 g) versus women who
      delivered an infant weighing >2,500 g in a large metropolitan county (Bexar) in
      South Texas. DESIGN: An exploratory case comparison design was used to identify
      factors related to LBW outcomes in women receiving prenatal care. SAMPLE: The
      cases were obtained from community hospitals. A stratified random sample was
      selected from a population of 38,064 infant births, of which 2,910 were
      identified as LBW. The final sample size was N=321 (<2,500 g, n=151; >or=2,500 g,
      n=170). MEASUREMENTS: Dependent variable of infant birth weight; independent
      variables of maternal age, maternal race/ethnicity, education, smoking, prior
      pregnancy history, timing of and number of prenatal visits, prepregnancy body
      mass index and weight gain during pregnancy, and past medical history and medical
      problems during pregnancy. RESULTS: Independent variables found to be predictive
      of LBW in this study included maternal race/ethnicity, timing of first prenatal
      visit, number of prenatal visits, prior pregnancy history, and maternal weight
      gain. CONCLUSIONS: This study confirmed previous findings that African American
      women are at a higher risk for LBW deliveries and demonstrated that Anglo and
      Hispanic women have similar rates of LBW deliveries.

PMID- 18816357
TI  - Deciding to opt out of childhood vaccination mandates.
AB  - OBJECTIVES: We explore the attitudes and beliefs of parents who consciously
      choose not to vaccinate their children and the ways in which these parents
      process information on the pros and cons of vaccines. DESIGN: In-depth,
      semistructured interviews were conducted. SAMPLE: The study population consisted
      of 25 parents who do not vaccinate their children, identified through snowball
      and targeted sampling. METHODS: Participants were asked about their processes and
      actions when choosing not to vaccinate their children. Interviews were taped and
      transcribed, and the content was analyzed for emergent themes. RESULTS: Two
      predominant themes emerged in our data: a desire to collect information on
      vaccines and trust issues with the medical community. Evidence of sophisticated
      data collection and information processing was a repeated theme in the interview
      data. Simultaneously, while participants placed a high value on scientific
      knowledge, they also expressed high levels of distrust of the medical community.
      CONCLUSIONS: The challenge for public health is to balance scientific data with
      popular epidemiology and to maintain legitimacy. Understanding the differences in
      lay versus expert knowledge has implications for crafting health messages. How
      experts frame knowledge for consumption has an important impact on this group and
      their decision-making processes.

PMID- 18816358
TI  - Relationship of symptoms, perceived health, and stigma with quality of life among
      urban HIV-infected African American men.
AB  - OBJECTIVES: To explore the relationship of symptom prevalence and intensity,
      perceptions of health, and stigma on quality of life (QOL) among HIV-infected
      African American men. DESIGN: Cross-sectional correlational descriptive study.
      SAMPLES: The sample consisted of HIV-infected African American men (N=55), all
      urban, age range 23-66 years (M=48.84, SD=7.67), average length of time since HIV
      diagnosis 10.79 years (SD=6.4). MEASUREMENTS: A questionnaire consisting of 5
      instruments was used: (a) sociodemographic characteristics, (b) Holzemer Signs
      and Symptom Checklist for HIV, (c) perceptions of health, (d) Berger HIV Stigma
      Scale, and (e) Holmes HIV/AIDS-Targeted Quality of Life Scale. RESULTS: Prevalent
      symptoms were fatigue (98%), fear (92.7%), shortness of breath (92.7%),
      gastrointestinal upset (85.5%), numbness (80.0%), and headache (76.4%). Symptoms
      with the highest intensity were gastrointestinal upset, body changes, fear, and
      fatigue. Symptom intensity was significantly associated with the measures of
      stigma and QOL. CONCLUSIONS: The results underscore the importance of
      incorporating a holistic view of the relationship of symptoms with QOL for HIV
      infected African American men. Without efforts to ameliorate stigmatizing
      effects, however, nurses may be falling short in helping individual African
      American men with HIV infection achieve a better QOL.

PMID- 18816359
TI  - Experiences of homeless people in the health care delivery system: a descriptive
      phenomenological study.
AB  - OBJECTIVE: The objective of this research is to understand the experiences of
      homeless people with the health care system. DESIGN: A descriptive
      Phenomenological research design is used. Phenomenology is the philosophical
      underpinning of this research. SAMPLE: The purposive sample consists of 15
      homeless adults. METHOD: Interviews were conducted, tape-recorded, transcribed,
      and then analyzed the transcripts using Colaizzi's descriptive phenomenological
      method. RESULTS: 4 major themes emerged: (1) living without essential resources
      compromises health; (2) putting off health care until a crisis arises; (3)
      encountering barriers to receiving health care to include (a) social triage, (b)
      feeling labeled and stigmatized, (c) a nonsystem for health care for the
      homeless, (d) being treated with disrespect, and (e) feeling invisible to health
      care providers; and (4) developing underground resourcefulness. CONCLUSIONS AND
      IMPLICATIONS: Although homeless persons articulated many problems in the health
      care system encounters, they also described their own resourcefulness and the
      strategies they employ to manage being marginalized by society and the health
      care system. An increased understanding of health care experiences from the
      homeless persons' perspective can guide public health nursing emancipatory
      actions.

PMID- 18816360
TI  - Strengthening new fathers' skills in interaction with their 5-month-old infants:
      who benefits from a brief intervention?
AB  - OBJECTIVES: To determine the utility of a parenting education program for fathers
      of infants, and to determine which fathers benefited. DESIGN: Fathers'
      perceptions of the program's utility were captured in a brief, structured
      interview. Using secondary data analysis, pretest/posttest father-infant
      interaction scores of fathers who improved were compared with those of fathers
      who did not. Demographic predictors of improvement were identified using multiple
      regression. SAMPLE: Community sample of 81 adult, English-speaking, primarily
      European Canadian, first-time fathers of 5-month-old infants, who participated in
      the intervention group of a randomized controlled trial. INTERVENTION: When
      infants were 5 and 6 months old, videotaped self-modeling and positive feedback
      about father-infant interaction were provided by specially trained nurses.
      MEASUREMENTS: Father-infant interaction was assessed at baseline (5 months) and
      outcome (8 months) using the Nursing Child Assessment Teaching Scale. RESULTS:
      Fathers found the program useful, indicating that their needs for educational
      programs are different from mothers. Controlling for baseline interactions,
      demographic variables did not significantly predict fathers' outcome
      interactions. CONCLUSIONS: The program may prove useful in public health settings
      where implementing programs for fathers of infants is a priority. Future research
      needs to explore other predictors to identify fathers who will benefit from the
      program.

PMID- 18816361
TI  - Influence of communicator's race on efficacy of an HIV/STD prevention
      intervention among African American and Caucasian college students.
AB  - OBJECTIVES: The present research examined the influence of communicator's race on
      the efficacy of intervention videos in the reduction of human immunodeficiency
      virus (HIV) and other sexually transmitted diseases (STDs) among African American
      and Caucasian college females. DESIGN: Experimental HIV/STD prevention digital
      versatile disks (DVDs) featured a White female as a primary or a secondary
      communicator relative to a Black female, while a control DVD featured 2 Black
      females. Respondents watched 1 DVD and completed questionnaires before and after
      viewing the DVD as well as 2 and 4 weeks later. SAMPLE: 79 African American
      females and 88 Caucasian females participated. MEASUREMENTS: Perceptions of the
      DVDs, HIV/STD risk, intentions to use condoms, and number of condoms purchased
      after viewing the videos were assessed. RESULTS: The intervention was effective
      in increasing intentions to use condoms with a current partner across the follow
      up periods. There was no effect of race of communicator on any variable for
      African American or Caucasians. CONCLUSIONS: While communicator's race did not
      affect this intervention, more research is necessary. Future studies should use
      multiple Black and White communicators to isolate the role of race and should be
      conducted where larger samples of African American college students can be
      recruited.

PMID- 18816362
TI  - Social support for physical activity of middle school students.
AB  - OBJECTIVE: To explore gender and age differences in social support and their
      relationship with physical activity. DESIGN AND SAMPLE: This cross-sectional
      study with enhanced reliability due to repeated measures involved 105 boys and
      101 girls. MEASUREMENTS: Information on sources and forms of social support, as
      well as physical activity, was obtained from students, who completed the same
      questionnaire twice, 2 weeks apart. RESULTS: Boys, compared with girls, were more
      likely to name fathers and less likely to identify sisters. Compared with older
      boys, older girls were less likely to identify fathers. Older girls were less
      likely than both younger girls and older boys to name brothers. Students who
      identified fathers reported more minutes and days of physical activity and had a
      stronger physical activity self-definition than those who did not name fathers.
      Students who selected peers and sisters had more minutes of physical activity and
      a stronger physical activity self-definition, respectively, than those who did
      not name peers and sisters. Transportation and encouragement were related to
      physical activity. CONCLUSIONS: Gender differences in social support are not
      uniform across age groups. Awareness of these differences can inform the
      development of appropriate physical activity programs.

PMID- 18816363
TI  - Culture brokerage strategies in diabetes education.
AB  - The purpose of this article is to describe the elements of culture brokerage as
      applied in a recent educational pilot study among rural African Americans with
      type 2 diabetes mellitus. Culture Brokerage is a nursing intervention consisting
      of mediation between the traditional health beliefs and practices of a patient's
      culture and the health care system. The intervention of Culture Brokerage holds
      particular relevance for clinicians who work with chronically ill patients,
      including those with diabetes. Diabetes prevalence rates continue to rise with
      alarming swiftness, affecting people of all age groups and ethnicities. The
      burden of disease, however, disproportionately falls on ethnic minority groups,
      including African Americans. Notable health disparities in the prevalence and
      long-term complications of diabetes warrant the attention of health care
      professionals. One way in which public health nurses can address these
      disparities is to apply strategies of culture brokerage.

PMID- 18816364
TI  - Factors affecting satisfaction levels of Japanese volunteers in meal delivery
      services for the elderly.
AB  - OBJECTIVES: The purpose of this study was to investigate the factors affecting
      satisfaction with volunteer work of participants in a meal delivery service for
      the elderly. DESIGN: A cross-sectional study with a self-administered survey was
      carried out. SAMPLE: Of 364 volunteers assisting with a meal delivery service for
      the elderly in rural towns A (80), B (159), and C (125), 247 responded (response
      rate: 68%). METHOD: An anonymous self-administered questionnaire survey was
      administered seeking information about basic attributes, sense of satisfaction
      with volunteer work, and working circumstances such as human relationships with
      fellow volunteers, meal service users or professional staff members,
      opportunities for meetings or workshop, publicity through public relations
      magazines, and the like. RESULTS: In multivariate logistic analysis, the sense of
      satisfaction of volunteers was closely associated with human relations among
      volunteers (odds ratio [OR] 5.15, 95% Confidence Interval (CI) 1.84-14.40,
      p<.01), meal service users (OR 3.84, 95% CI 1.37-10.77, p<.05), and professional
      staff members supervising the meal delivery service (OR 3.53, 95% CI 1.27-9.84,
      p<.05). Human relations were also affected by the emphasis on communication,
      consultation with supervisory staff members, having opportunities for meetings,
      having friends with whom to confer, and publicity through public relations
      magazines. CONCLUSION: Satisfaction levels of volunteers in meal delivery
      services for the elderly were most affected by human relations with fellow
      volunteers, meal service users, and professional staff members. Increasing
      opportunities for communication may be important to promote good human
      relationships among volunteers and volunteer activities.

PMID- 18816366
TI  - Home or nursing home: does place of residence affect longevity in patients with
      Alzheimer's disease? The experience of CERAD patients.
AB  - There is concern that life is curtailed when patients with Alzheimer's disease
      (AD) are institutionalized. To determine whether placement in a nursing home
      reduces their remaining years of life, we examined the experience of White
      patients with AD (n=890) enrolled in the Consortium to Establish a Registry for
      Alzheimer's Disease (CERAD). Proportional hazards survival analysis using the
      landmark approach (with the landmark set to 12 months after CERAD entry and
      reevaluated at succeeding 6-month time intervals through 5 years) indicated that
      longevity at home and in the nursing home was comparable. Thus, in these patients
      enrolled at tertiary care medical centers, living at home or in a nursing home
      did not affect time to death. These data suggest that when home care is no longer
      feasible, families and nurses counseling them should not feel that they are
      curtailing life by placing an AD patient in a nursing home.

PMID- 18816365
TI  - Translation of the multidimensional health locus of control scales for users of
      American sign language.
AB  - This paper describes the translation of the Multidimensional Health Locus of
      Control (MHLC) scales into American Sign Language (ASL). Translation is an
      essential first step toward validating the instrument for use in the Deaf
      community, a commonly overlooked minority community. This translated MHLC/ASL can
      be utilized by public health nurses researching the Deaf community to create and
      evaluate targeted health interventions. It can be used in clinical settings to
      guide the context of the provider-patient dialogue. The MHLC was translated using
      focus groups, following recommended procedures. 5 bilingual participants
      translated the MHLC into ASL; 5 others back-translated the ASL version into
      English. Both focus groups identified and addressed language and cultural
      problems before the final ASL version of the MHLC was permanently captured by
      motion picture photography for consistent administration. Nine of the 24 items
      were directly translatable into ASL. The remaining items required further
      discussion to achieve cultural equivalence with ASL expressions. The MHLC/ASL is
      now ready for validation within the Deaf community.

PMID- 18816367
TI  - Legacy leadership: the Beverly Flynn Public Health Nursing Mentorship: tribute to
      a nursing mentor.
AB  - The manuscript presents the background and history of the Beverly C. Flynn Legacy
      Leadership Award sponsored by the American Public Health Association's (APHA)
      Public Health Nursing Section. The Flynn Legacy Leadership program recognizes
      graduate students majoring in public health/community health nursing, and novice
      public health nurses for their potential to be future leaders in public health
      nursing. The importance of the mentoring relationship in promoting the standards
      of practice for public health nursing is explored. The Flynn Legacy Leadership
      Program fosters meaningful connections in the public health nursing community
      beyond the scope of the annual meeting. Award winners from the three years of the
      program are showcased with examples of scholarship fostered through the Beverly
      C. Flynn Legacy Leadership Award.

PMID- 18816368
TI  - Experimental observations of rapid Maize streak virus evolution reveal a strand
      specific nucleotide substitution bias.
AB  - BACKGROUND: Recent reports have indicated that single-stranded DNA (ssDNA)
      viruses in the taxonomic families Geminiviridae, Parvoviridae and Anellovirus may
      be evolving at rates of approximately 10(-4) substitutions per site per year
      (subs/site/year). These evolution rates are similar to those of RNA viruses and
      are surprisingly high given that ssDNA virus replication involves host DNA
      polymerases with fidelities approximately 10,000 times greater than those of
      error-prone viral RNA polymerases. Although high ssDNA virus evolution rates were
      first suggested in evolution experiments involving the geminivirus maize streak
      virus (MSV), the evolution rate of this virus has never been accurately measured.
      Also, questions regarding both the mechanistic basis and adaptive value of high
      geminivirus mutation rates remain unanswered. RESULTS: We determined the short
      term evolution rate of MSV using full genome analysis of virus populations
      initiated from cloned genomes. Three wild type viruses and three defective
      artificial chimaeric viruses were maintained in planta for up to five years and
      displayed evolution rates of between 7.4 x 10(-4) and 7.9 x 10-4 subs/site/year.
      CONCLUSION: These MSV evolution rates are within the ranges observed for other
      ssDNA viruses and RNA viruses. Although no obvious evidence of positive selection
      was detected, the uneven distribution of mutations within the defective virus
      genomes suggests that some of the changes may have been adaptive. We also
      observed inter-strand nucleotide substitution imbalances that are consistent with
      a recent proposal that high mutation rates in geminiviruses (and possibly ssDNA
      viruses in general) may be due to mutagenic processes acting specifically on
      ssDNA molecules.

PMID- 18816369
TI  - Familiarity between patient and general practitioner does not influence the
      content of the consultation.
AB  - BACKGROUND: Personal continuity in general practice is considered to be a
      prerequisite of high quality patient care based on shared knowledge and mutual
      understanding. Not much is known about how personal continuity is reflected in
      the content of GP - patient communication. We explored whether personal
      continuity of care influences the content of communication during the
      consultation. METHODS: Personal continuity was defined as the degree of
      familiarity between GP and patient, rated by both the GP and the patient. 394
      videotaped consultations between GPs and patients aged 18 years and older were
      analyzed. GP - patient communication was evaluated with an observation checklist,
      which rated the following topics of conversation: (1) medical issues, (2)
      psychological themes, and (3) the social environment of the patient. For each of
      these topics we coded whether or not it received attention, and was built upon
      prior knowledge. Data were analyzed using multilevel logistic regression
      analyses. RESULTS: No relationship was found between GP - patient familiarity and
      the discussion of medical issues, psychological themes, or the social environment
      of the patient. But if the patient and the GP knew each other very well, the GP
      more often displayed prior knowledge with the topic in question. Few patient and
      GP characteristics were associated with differences in content of communication.
      CONCLUSION: Given the relatively small sample size, we carefully conclude that
      familiarity between a GP and a patient does not influence the content of the
      communication (medical issues, psychological themes nor topics relating to the
      social environment). This is remarkable because we expected that familiarity
      would 'open up the communication' for more psychological and social themes. GPs
      seem to have the communication skills to put both familiar and non-familiar
      patients at ease enabling them to freely raise any issue they think necessary.

PMID- 18816370
TI  - Immunity, ageing and cancer.
AB  - Compromised immunity contributes to the decreased ability of the elderly to
      control infectious disease and to their generally poor response to vaccination.
      It is controversial as to how far this phenomenon contributes to the well-known
      age-associated increase in the occurrence of many cancers in the elderly.
      However, should the immune system be important in controlling cancer, for which
      there is a great deal of evidence, it is logical to propose that dysfunctional
      immunity in the elderly would contribute to compromised immunosurveillance and
      increased cancer occurrence. The chronological age at which immunosenescence
      becomes clinically important is known to be influenced by many factors, including
      the pathogen load to which individuals are exposed throughout life. It is
      proposed here that the cancer antigen load may have a similar effect on "immune
      exhaustion" and that pathogen load and tumor load may act additively to
      accelerate immunosenescence. Understanding how and why immune responsiveness
      changes in humans as they age is essential for developing strategies to prevent
      or restore dysregulated immunity and assure healthy longevity, clearly possible
      only if cancer is avoided. Here, we provide an overview of the impact of age on
      human immune competence, emphasizing T-cell-dependent adaptive immunity, which is
      the most sensitive to ageing. This knowledge will pave the way for rational
      interventions to maintain or restore appropriate immune function not only in the
      elderly but also in the cancer patient.

PMID- 18816371
TI  - A pilot study using Tissue Velocity Ultrasound Imaging (TVI) to assess muscle
      activity pattern in patients with chronic trapezius myalgia.
AB  - BACKGROUND: Different research techniques indicate alterations in muscle tissue
      and in neuromuscular control of aching muscles in patients with chronic localized
      pain. Ultrasound can be used for analysis of muscle tissue dynamics in clinical
      practice. AIM: This study introduces a new muscle tissue sensitive ultrasound
      technique in order to provide a new methodology for providing a description of
      local muscle changes. This method is applied to investigate trapezius muscle
      tissue response - especially with respect to specific regional deformation and
      deformation rates - during concentric shoulder elevation in patients with chronic
      trapezius myalgia and healthy controls before and after pain provocation.
      METHODS: Patients with trapezius myalgia and healthy controls were analyzed using
      an ultrasound system equipped with tissue velocity imaging (TVI). The patients
      performed a standardized 3-cm concentric shoulder elevation before and after pain
      provocation/exercise at a standardized elevation tempo (30 bpm). A standardized
      region of interest (ROI), an ellipsis with a size that captures the upper and
      lower fascia of the trapezius muscle (4 cm width) at rest, was placed in the
      first frame of the loop registration of the elevation. The ROI was re-anchored
      frame by frame following the same anatomical landmark in the basal fascia during
      all frames of the concentric phase. In cardiac measurement, tissue velocities are
      measured in the axial projection towards and against the probe where red colour
      represents shortening and red lengthening. In the case of measuring the trapezius
      muscle, tissue deformation measurements are made orthogonally, thus, indirectly.
      Based on the assumption of muscle volume incompressibility, blue represents
      tissue contraction and red relaxation. Within the ROI, two variables were
      calculated as a function of time: deformation and deformation rate. Hereafter,
      max, mean, and quadratic mean values (RMS) of each variable were calculated and
      compared before and after pain provocation/exercise. RESULTS: This new
      methodology seems valuable when looking at local muscle changes and studying the
      mechanism behind chronic muscle pain. The univariate analyses indicate that
      patients with chronic trapezius myalgia after pain provocation due to exercise at
      group level showed decreased strain and unchanged strain rate while healthy
      controls had unchanged strain and increased strain rate. However, the
      multivariate analysis indicates that most patients showed lower levels according
      to both strain and strain rate after exercise compared to most controls.
      CONCLUSION: Tissue velocity imaging can help describe musculoskeletal tissue
      activity and dynamics in patients with chronic pain conditions. An altered muscle
      tissue dynamic after pain provocation/exercise among the majority of trapezius
      myalgia patients compared with the healthy controls was found.

PMID- 18816372
TI  - Prevalence of obesity and abdominal obesity in the Lausanne population.
AB  - BACKGROUND: Obesity can be defined using body mass index (BMI) or waist
      (abdominal obesity). Little information exists regarding its prevalence and
      determinants in Switzerland. Hence, we assessed the levels of obesity as defined
      by BMI or waist circumference in a Swiss population-based sample. METHODS: Cross
      sectional, population-based non-stratified random sample of 3,249 women and 2,937
      men aged 35-75 years living in Lausanne, Switzerland. Overall participation rate
      was 41%. RESULTS: In men, the prevalences of overweight (BMI > or =25 kg/m2) and
      obesity (BMI > or =30 kg/m2) were 45.5% and 16.9%, respectively, higher than in
      women (28.3% and 14.3%, respectively). The prevalence of abdominal obesity (waist
      > or =102 in men and > or =88 cm in women) was higher in women than in men (30.6%
      vs. 23.9%). Obesity and abdominal obesity increased with age and decreased with
      higher educational level in both genders. In women, the prevalence of obesity was
      lower among former and current smokers, whereas in men the prevalence of obesity
      was higher in former smokers but did not differ between current and never
      smokers. Multivariate analysis showed age to be positively related, and education
      and physical activity to be negatively related with obesity and abdominal obesity
      in both genders, whereas differential effects of smoking were found between
      genders. CONCLUSION: The prevalence of abdominal obesity is higher than BMI
      derived obesity in the Swiss population. Women presented with more abdominal
      obesity than men. The association between smoking and obesity levels appears to
      differ between genders.

PMID- 18816373
TI  - Bed net ownership, use and perceptions among women seeking antenatal care in
      Kinshasa, Democratic Republic of the Congo (DRC): opportunities for improved
      maternal and child health.
AB  - BACKGROUND: To describe malaria knowledge, attitudes toward malaria and bed net
      use, levels of ownership and use of bed nets, and factors associated with
      ownership and use among pregnant women attending their first antenatal care (ANC)
      visit in Kinshasa, DRC. METHODS: Women attending their first ANC visit at one
      maternity in Kinshasa were recruited to take part in a study where they were
      given free insecticide treated bed nets (ITNs) and then followed up at delivery
      and 6 months post delivery to assess ITN use. This study describes the baseline
      levels of bed net ownership and use, attitudes towards net use and factors
      associated with net use RESULTS: Among 351 women interviewed at baseline, 115
      (33%) already owned a bed net and 86 (25%) reported to have slept under the net
      the previous night. Cost was reported as the reason for not owning a net by 48%
      of the 236 women who did not own one. In multivariable analyses, women who had
      secondary school or higher education were 3.4 times more likely to own a net (95%
      CI 1.6-7.3) and 2.8 times more likely to have used a net (95% CI 1.3-6.0)
      compared to women with less education CONCLUSION: Distribution of ITNs in
      antenatal clinics in this setting is needed and feasible. The potential for ITN
      use by this target population is high.

PMID- 18816374
TI  - Pattern of humoral immune response to Plasmodium falciparum blood stages in
      individuals presenting different clinical expressions of malaria.
AB  - BACKGROUND: The development of protective immunity against malaria is slow and to
      be maintained, it requires exposure to multiple antigenic variants of malaria
      parasites and age-associated maturation of the immune system. Evidence that the
      protective immunity is associated with different classes and subclasses of
      antibodies reveals the importance of considering the quality of the response. In
      this study, we have evaluated the humoral immune response against Plasmodium
      falciparum blood stages of individuals naturally exposed to malaria who live in
      endemic areas of Brazil in order to assess the prevalence of different specific
      isotypes and their association with different malaria clinical expressions.
      METHODS: Different isotypes against P. falciparum blood stages, IgG, IgG1, IgG2,
      IgG3, IgG4, IgM, IgE and IgA, were determined by ELISA. The results were based on
      the analysis of different clinical expressions of malaria (complicated,
      uncomplicated and asymptomatic) and factors related to prior malaria exposure
      such as age and the number of previous clinical malaria attacks. The occurrence
      of the H131 polymorphism of the FcgammaIIA receptor was also investigated in part
      of the studied population. RESULTS: The highest levels of IgG, IgG1, IgG2 and
      IgG3 antibodies were observed in individuals with asymptomatic and uncomplicated
      malaria, while highest levels of IgG4, IgE and IgM antibodies were predominant
      among individuals with complicated malaria. Individuals reporting more than five
      previous clinical malaria attacks presented a predominance of IgG1, IgG2 and IgG3
      antibodies, while IgM, IgA and IgE antibodies predominated among individuals
      reporting five or less previous clinical malaria attacks. Among individuals with
      uncomplicated and asymptomatic malaria, there was a predominance of high-avidity
      IgG, IgG1, IgG2 antibodies and low-avidity IgG3 antibodies. The H131 polymorphism
      was found in 44.4% of the individuals, and the highest IgG2 levels were observed
      among asymptomatic individuals with this allele, suggesting the protective role
      of IgG2 in this population. CONCLUSION: Together, the results suggest a
      differential regulation in the anti-P. falciparum antibody pattern in different
      clinical expressions of malaria and showed that even in unstable transmission
      areas, protective immunity against malaria can be observed, when the appropriated
      antibodies are produced.

PMID- 18816375
TI  - Development of a luciferase-based reporter system to monitor Bifidobacterium
      breve UCC2003 persistence in mice.
AB  - BACKGROUND: Probiotics such as bifidobacteria have been shown to maintain a
      healthy intestinal microbial balance and help protect against infections.
      However, despite these benefits, bifidobacteria still remain poorly understood at
      the biochemical, physiological and especially the genetic level. Herein we
      describe, for the first time, the development of a non-invasive luciferase-based
      reporter system for real-time tracking of Bifidobacterium species in vivo.
      RESULTS: The reporter vector pLuxMC1 is based on the recently described theta
      type plasmid pBC1 from B. catenatulatum 1 and the luxABCDE operon from pPL2lux 2.
      Derivatives of pLuxMC1, harbouring a bifidobacterial promoter (pLuxMC2) as well
      as a synthetically derived promoter (pLuxMC3) 3 placed upstream of luxABCDE, were
      constructed and found to stably replicate in B. breve UCC2003. The subsequent
      analysis of these strains allowed us to assess the functionality of pLuxMC1 both
      in vitro and in vivo. CONCLUSION: Our results demonstrate the potential of
      pLuxMC1 as a real-time, non-invasive reporter system for Bifidobacterium. It has
      also allowed us, for the first time, to track the colonisation potential and
      persistence of this probiotic species in real time. An interesting and
      significant outcome of the study is the identification of the caecum as a niche
      environment for B. breve UCC2003 within the mouse gastrointestinal tract (GI)
      tract.

PMID- 18816376
TI  - Surgical difficulties for Total Knee Replacement in Stickler syndrome: A case
      report.
AB  - Stickler syndrome is believed to be the most common connective tissue disorder
      in Europe and the USA. Severe osteoarthritis sets in at very early age in 3rd to
      4th decade of life necessitating joint arthroplasty. This case report highlights
      the intraoperative surgical difficulties faced by the surgeon and the planning
      needed for the operation.

PMID- 18816377
TI  - The chemokine CXCL1/growth related oncogene increases sodium currents and
      neuronal excitability in small diameter sensory neurons.
AB  - BACKGROUND: Altered Na+ channel expression, enhanced excitability, and
      spontaneous activity occur in nerve-injury and inflammatory models of
      pathological pain, through poorly understood mechanisms. The cytokine GRO/KC
      (growth related oncogene; CXCL1) shows strong, rapid upregulation in dorsal root
      ganglion in both nerve injury and inflammatory models. Neurons and glia express
      its receptor (CXCR2). CXCL1 has well-known effects on immune cells, but little is
      known about its direct effects on neurons. RESULTS: We report that GRO/KC
      incubation (1.5 nM, overnight) caused marked upregulation of Na+ currents in
      acutely isolated small diameter rat (adult) sensory neurons in vitro. In both IB4
      positive and IB4-negative sensory neurons, TTX-resistant and TTX-sensitive
      currents increased 2- to 4 fold, without altered voltage dependence or kinetic
      changes. These effects required long exposures, and were completely blocked by co
      incubation with protein synthesis inhibitor cycloheximide. Amplification of cDNA
      from the neuronal cultures showed that 3 Na channel isoforms were predominant
      both before and after GRO/KC treatment (Nav 1.1, 1.7, and 1.8). TTX-sensitive
      isoforms 1.1 and 1.7 significantly increased 2 - 3 fold after GRO/KC incubation,
      while 1.8 showed a trend towards increased expression. Current clamp experiments
      showed that GRO/KC caused a marked increase in excitability, including resting
      potential depolarization, decreased rheobase, and lower action potential
      threshold. Neurons acquired a striking ability to fire repetitively; IB4-positive
      cells also showed marked broadening of action potentials. Immunohistochemical
      labelling confirmed that the CXCR2 receptor was present in most neurons both in
      dissociated cells and in DRG sections, as previously shown for neurons in the
      CNS. CONCLUSION: Many studies on the role of chemokines in pain conditions have
      focused on their rapid and indirect effects on neurons, via release of
      inflammatory mediators from immune and glial cells. Our study suggests that
      GRO/KC may also have important pro-nociceptive effects via its direct actions on
      sensory neurons, and may induce long-term changes that involve protein synthesis.

PMID- 18816378
TI  - Clearing up the hazy road from bench to bedside: a framework for integrating the
      fourth hurdle into translational medicine.
AB  - BACKGROUND: New products evolving from research and development can only be
      translated to medical practice on a large scale if they are reimbursed by third
      party payers. Yet the decision processes regarding reimbursement are highly
      complex and internationally heterogeneous. This study develops a process-oriented
      framework for monitoring these so-called fourth hurdle procedures in the context
      of product development from bench to bedside. The framework is suitable both for
      new drugs and other medical technologies. METHODS: The study is based on expert
      interviews and literature searches, as well as an analysis of 47 websites of
      coverage decision-makers in England, Germany and the USA. RESULTS: Eight key
      steps for monitoring fourth hurdle procedures from a company perspective were
      determined: entering the scope of a healthcare payer; trigger of decision
      process; assessment; appraisal; setting level of reimbursement; establishing
      rules for service provision; formal and informal participation; and publication
      of the decision and supplementary information. Details are given for the English
      National Institute for Health and Clinical Excellence, the German Federal Joint
      Committee, Medicare's National and Local Coverage Determinations, and for Blue
      Cross Blue Shield companies. CONCLUSION: Coverage determination decisions for new
      procedures tend to be less formalized than for novel drugs. The analysis of
      coverage procedures and requirements shows that the proof of patient benefit is
      essential. Cost-effectiveness is likely to gain importance in future.

PMID- 18816379
TI  - A novel reverse transduction adenoviral array for the functional analysis of
      shRNA libraries.
AB  - BACKGROUND: The identification of novel drug targets by assessing gene functions
      is most conveniently achieved by high-throughput loss-of-function RNA
      interference screening. There is a growing need to employ primary cells in such
      screenings, since they reflect the physiological situation more closely than
      transformed cell lines do. Highly miniaturized and parallelized approaches as
      exemplified by reverse transfection or transduction arrays meet these
      requirements, hence we verified the applicability of an adenoviral microarray for
      the elucidation of gene functions in primary cells. RESULTS: Here, we present
      microarrays of infectious adenoviruses encoding short hairpin RNA (shRNA) as a
      new tool for gene function analysis. As an example to demonstrate its
      application, we chose shRNAs directed against seven selected human protein
      kinases, and we have performed quantitative analysis of phenotypical responses in
      primary human umbilical vein cells (HUVEC). These microarrays enabled us to
      infect the target cells in a parallelized and miniaturized procedure without
      significant cross-contamination: Viruses were reversibly immobilized in spots in
      such a way that the seeded cells were confined to the area of the viral spots,
      thus simplifying the subsequent addressing of genetically modified cells for
      analysis. Computer-assisted image analysis of fluorescence images was applied to
      analyze the cellular response after shRNA expression. Both the expression level
      of knock-down target proteins as well as the functional output as measured by
      caspase 3 activity and DNA fractionation (TUNEL) were quantified. CONCLUSION: We
      have developed an adenoviral microarray technique suitable for miniaturized and
      parallelized analysis of gene function. The practicability of this technique was
      demonstrated by the analysis of several kinases involved in the activation of
      programmed cell death, both in tumor cells and in primary cells.

PMID- 18816380
TI  - Did the post war repatriation of Lebanese physicians drive recent Lebanese
      medical graduates to emigrate? An observational study.
AB  - BACKGROUND: A significant number of Lebanese medical graduates have emigrated
      from Lebanon. The objective of this study was to evaluate the hypothesis that the
      repatriation of Lebanese physicians educated abroad has contributed to the
      international emigration of recent Lebanese medical graduates. METHODS: We
      analyzed the demographic and educational characteristics and the year of
      registration of physicians registered with the two physician associations in
      Lebanon as of 2007. We then analyzed the number of new and total registrants and
      the physician density for the years 1977-2006. Finally we calculated the
      percentage of Lebanese graduates of the years 1977-2006 registered as of 2007.
      RESULTS: As of 2007, 10,918 physicians were registered in Lebanon. Most were male
      (80.4%) and graduated from either Lebanese (36.4%) or Eastern European (30.6%)
      medical schools. The top three regions of specialty training were Western Europe
      (31.8%), Eastern Europe (28.4%) and Lebanon (25.7%). About half the physicians
      registered with the Lebanese Order of Physicians as of 2007 joined during the
      1990 s decade; only 26.2% of these graduated from Lebanese medical schools during
      that decade. The number of new registrants increased dramatically in the early
      1990 s and started decreasing in the early 2000s. About 60% of Lebanese medical
      graduates of the years 1977-2006 were registered in Lebanon as of 2007.
      Categorizing Lebanese medical graduates by their year of graduation, the
      percentage registered in Lebanon as of 2007 showed a "dip" for those who
      graduated in the early 1990 s. CONCLUSION: The high number of physicians educated
      abroad returning to Lebanon after the end of the civil war may have driven recent
      Lebanese medical graduates to emigrate.

PMID- 18816381
TI  - Process factors explaining the ineffectiveness of a multidisciplinary fall
      prevention programme: a process evaluation.
AB  - BACKGROUND: Falls are a major health threat to older community-living people, and
      initiatives to prevent falls should be a public health priority. We evaluated a
      Dutch version of a successful British fall prevention programme. Results of this
      Dutch study showed no effects on falls or daily functioning. In parallel to the
      effect evaluation, we carried out a detailed process evaluation to assess the
      feasibility of our multidisciplinary fall prevention programme. The present study
      reports on the results of this process evaluation. METHODS: Our fall prevention
      programme comprised a medical and occupational-therapy assessment, resulting in
      recommendations and/or referrals to other services if indicated. We used self
      administered questionnaires, structured telephone interviews, structured
      recording forms, structured face-to-face interviews and a plenary group
      discussion to collect data from participants allocated to the intervention group
      (n = 166) and from all practitioners who performed the assessments (n = 8). The
      following outcomes were assessed: the extent to which the multidisciplinary fall
      prevention programme was performed according to protocol, the nature of the
      recommendations and referrals provided to the participants, participants' self
      reported compliance and participants' and practitioners' opinions about the
      programme. RESULTS: Both participants and practitioners judged the programme to
      be feasible. The programme was largely performed according to protocol. The
      number of referrals and recommendations ensuing from the medical assessment was
      relatively small. Participants' self-reported compliance as regards contacting
      their GP to be informed of the recommendations and/or referrals was low to
      moderate. However, self-reported compliance with such referrals and
      recommendations was reasonable to good. A large majority of participants reported
      they had benefited from the programme. CONCLUSION: The results of the present
      study show that the programme was feasible for both practitioners and
      participants. Main factors that seem to be responsible for the lack of
      effectiveness are the relatively low number of referrals and recommendations
      ensuing from the medical assessments and participants' low compliance as regards
      contacting their GP about the results of the medical assessment. We do not
      recommend implementing the programme in its present form in regular care. TRIAL
      REGISTRATION: ISRCTN64716113.

PMID- 18816382
TI  - Comprehensive study of proteasome inhibitors against Plasmodium falciparum
      laboratory strains and field isolates from Gabon.
AB  - BACKGROUND: The emergence and spread of Plasmodium falciparum resistance to
      almost all available antimalarial drugs necessitates the search for new
      chemotherapeutic compounds. The ubiquitin/proteasome system plays a major role in
      overall protein turnover, especially in fast dividing eukaryotic cells including
      plasmodia. Previous studies show that the 20S proteasome is expressed and
      catalytically active in plasmodia and treatment with proteasome inhibitors
      arrests parasite growth. This is the first comprehensive screening of proteasome
      inhibitors with different chemical modes of action against laboratory strains of
      P. falciparum. Subsequently, a selection of inhibitors was tested in field
      isolates from Lambarene, Gabon. METHODS: Epoxomicin, YU101, YU102, MG132, MG115,
      Z-L(3)-VS, Ada-Ahx(3)-L(3)-VS, lactacystin, bortezomib (Velcade), gliotoxin, PR11
      and PR39 were tested and compared to chloroquine- and artesunate-activities in a
      standardized in vitro drug susceptibility assay against P. falciparum laboratory
      strains 3D7, D10 and Dd2. Freshly obtained field isolates from Lambarene, Gabon,
      were used to measure the activity of chloroquine, artesunate, epoxomicin, MG132,
      lactacystin and bortezomib. Parasite growth was detected through histidine-rich
      protein 2 (HRP2) production. Raw data were fitted by a four-parameter logistic
      model and individual inhibitory concentrations (50%, 90%, and 99%) were
      calculated. RESULTS: Amongst all proteasome inhibitors tested, epoxomicin showed
      the highest activity in chloroquine-susceptible (IC50: 6.8 nM [3D7], 1.7 nM
      [D10]) and in chloroquine-resistant laboratory strains (IC50: 10.4 nM [Dd2]) as
      well as in field isolates (IC50: 8.5 nM). The comparator drug artesunate was even
      more active (IC50: 1.0 nM), whereas all strains were chloroquine-resistant (IC50:
      113 nM). CONCLUSION: The peptide alpha',beta'-epoxyketone epoxomicin is highly
      active against P. falciparum regardless the grade of the parasite's chloroquine
      susceptibility. Therefore, inhibition of the proteasome is a highly promising
      strategy to develop new antimalarials. Epoxomicin can serve as a standard to
      compare new inhibitors with species-specific activity.

PMID- 18816383
TI  - Familial hypomagnesaemia with hypercalciuria and nephrocalcinosis (FHHNC):
      compound heterozygous mutation in the claudin 16 (CLDN16) gene.
AB  - BACKGROUND: Familial hypomagnesaemia with hypercalciuria and nephrocalcinosis
      (FHHNC) is an autosomal recessive disorder of renal calcium and magnesium wasting
      frequently complicated by progressive chronic renal failure in childhood or
      adolescence. METHODS: A 7 year old boy was investigated following the findings of
      marked renal insufficiency and nephrocalcinosis in his 18-month old sister. He
      too was found to have extensive nephrocalcinosis with increased fractional
      excretion of magnesium: 12.4% (<4%) and hypercalciuria: 5.7 mmol (< 2.5/24
      hours). He had renal impairment, partial distal renal tubular acidosis and
      defective urinary concentrating ability. Therapy with thiazide diuretics and
      magnesium supplements failed to halt the progression of the disorder. Both
      children subsequently underwent renal transplantation. Both children's parents
      are unaffected and there is one unaffected sibling. RESULTS: Mutation analysis
      revealed 2 heterozygous mutations in the claudin 16 gene (CLDN16) in both
      affected siblings; one missense mutation in exon 4: C646T which results in an
      amino acid change Arg216Cys in the second extracellular loop of CLDN16 and loss
      of function of the protein and a donor splice site mutation which changes intron
      4 consensus splice site from 'GT' to 'TT' resulting in decreased splice
      efficiency and the formation of a truncated protein with loss of 64 amino acids
      in the second extracellular loop. CONCLUSION: The mutations in CLDN16 in this
      kindred affect the second extra-cellular loop of claudin 16. The clinical course
      and molecular findings suggest complete loss of function of the protein in the 2
      affected cases and highlight the case for molecular diagnosis in individuals with
      FHHNC.

PMID- 18816384
TI  - Impairment of the CD8+ T cell response in lungs following infection with human
      respiratory syncytial virus is specific to the anatomical site rather than the
      virus, antigen, or route of infection.
AB  - BACKGROUND: A subset of the virus-specific CD8+ cytotoxic T lymphocytes (CTL)
      isolated from the lungs of mice infected with human respiratory syncytial virus
      (RSV) is impaired in the ability to secrete interferon gamma (IFNgamma), a
      measure of functionality. It was suggested that the impairment specifically
      suppressed the host cellular immune response, a finding that could help explain
      the ability of RSV to re-infect throughout life. RESULTS: To determine whether
      this effect is dependent on the virus, the route of infection, or the type of
      infection (respiratory, disseminated, or localized dermal), we compared the CTL
      responses in mice following intranasal (IN) infection with RSV or influenza virus
      or IN or intradermal (ID) infection with vaccinia virus expressing an RSV CTL
      antigen. The impairment was observed in the lungs after IN infection with RSV,
      influenza or vaccinia virus, and after a localized ID infection with vaccinia
      virus. In contrast, we observed a much higher percentage of IFNgamma secreting
      CD8+ lymphocytes in the spleens of infected mice in every case. CONCLUSION: The
      decreased functionality of CD8+ CTL is specific to the lungs and is not dependent
      on the specific virus, viral antigen, or route of infection.

PMID- 18816385
TI  - FAF-Drugs2: free ADME/tox filtering tool to assist drug discovery and chemical
      biology projects.
AB  - BACKGROUND: Drug discovery and chemical biology are exceedingly complex and
      demanding enterprises. In recent years there are been increasing awareness about
      the importance of predicting/optimizing the absorption, distribution, metabolism,
      excretion and toxicity (ADMET) properties of small chemical compounds along the
      search process rather than at the final stages. Fast methods for evaluating ADMET
      properties of small molecules often involve applying a set of simple empirical
      rules (educated guesses) and as such, compound collections' property profiling
      can be performed in silico. Clearly, these rules cannot assess the full
      complexity of the human body but can provide valuable information and assist
      decision-making. RESULTS: This paper presents FAF-Drugs2, a free adaptable tool
      for ADMET filtering of electronic compound collections. FAF-Drugs2 is a command
      line utility program (e.g., written in Python) based on the open source chemistry
      toolkit OpenBabel, which performs various physicochemical calculations,
      identifies key functional groups, some toxic and unstable molecules/functional
      groups. In addition to filtered collections, FAF-Drugs2 can provide, via Gnuplot,
      several distribution diagrams of major physicochemical properties of the screened
      compound libraries. CONCLUSION: We have developed FAF-Drugs2 to facilitate
      compound collection preparation, prior to (or after) experimental screening or
      virtual screening computations. Users can select to apply various filtering
      thresholds and add rules as needed for a given project. As it stands, FAF-Drugs2
      implements numerous filtering rules (23 physicochemical rules and 204
      substructure searching rules) that can be easily tuned.

PMID- 18816386
TI  - Determination Of The Efficacy And Side-effect Profile Of Lower Doses Of
      Intrathecal Morphine In Patients Undergoing Total Knee Arthroplasty.
AB  - BACKGROUND: Intrathecal (IT) morphine provides excellent post-operative
      analgesia, but causes multiple side effects including nausea and vomiting (PONV),
      pruritus and respiratory depression, particularly at higher doses. The lowest
      effective dose of spinal morphine in patients undergoing total knee arthroplasty
      is not known. METHODS: We evaluated the analgesic efficacy and side effect
      profile of 100 - 300 MUg IT morphine in patients undergoing elective total knee
      replacement in this prospective, randomized, controlled, double-blind study.
      Sixty patients over the age of 60 undergoing elective knee arthroplasty were
      enrolled. Patients were randomized to receive spinal anaesthesia with 15 mg
      Bupivacaine and IT morphine in three groups: (i) 100 MUg; (ii) 200 MUg; and (iii)
      300 MUg. RESULTS: Both 200 MUg and 300 MUg IT morphine provided comparable levels
      of postoperative analgesia. However, patients that received 100 MUg had greater
      pain postoperatively, with higher pain scores and a greater requirement for
      supplemental morphine. There were no differences between groups with regard to
      PONV, pruritus, sedation, respiratory depression or urinary retention.
      CONCLUSION: Both 200 MUg and 300 MUg provided comparable postoperative analgesia,
      which was superior to that provided by 100 mug IT morphine in patients undergoing
      total knee arthroplasty. Based on these findings, we recommend that 200 MUg IT
      morphine be used in these patients. TRIAL REGISTRATION: ClinicalTrials.gov
      Identifier NCT00695045.

PMID- 18816387
TI  - A large waterborne outbreak of campylobacteriosis in Norway: the need to focus on
      distribution system safety.
AB  - BACKGROUND: On 7 May 2007 the medical officer in Roros (population 5600) reported
      15 patients with gastroenteritis. Three days later he estimated hundreds being
      ill. Untreated tap water from a groundwater source was suspected as the vehicle
      and chlorination was started 11 May. Campylobacter was isolated from patients'
      stool samples. We conducted an investigation to identify the source and describe
      the extent of the outbreak. METHODS: We undertook a retrospective cohort study
      among a random sample of customers of Roros and neighbouring Holtalen waterworks.
      Holtalen, which has a different water source, was used as a control city. We
      conducted telephone interviews to gather data on illness from all household
      members. One randomly selected household member was asked about detailed exposure
      history. The regional hospital laboratory tested patients' stools for
      enteropathogens. Campylobacter isolates were typed by AFLP for genetic similarity
      at the Norwegian Institute of Public Health. Local authorities conducted the
      environmental investigation. RESULTS: We identified 105 cases among 340
      individuals from Roros and Holtalen (Attack Rate = 31%). Tap water consumption
      was the only exposure associated with illness. Among randomly selected household
      members from Roros, a dose-response relationship was observed in daily consumed
      glasses of tap water (chi2 for trend = 8.1, p = 0.004). Campylobacter with
      identical AFLP was isolated from 25 out of 26 submitted stool samples. No
      pathogens were detected in water samples. We identified several events that might
      have caused pressure fall and influx of contaminated water into the water
      distribution system. On two occasions, pressure fall was noticed and parts of the
      distribution system were outdated. CONCLUSION: The investigation confirmed a
      waterborne outbreak of campylobacteriosis in Roros. Although no single event was
      identified as the cause of contamination, this outbreak illustrates the
      vulnerability of water distribution systems. Good quality source water alone is
      not enough to ensure water safety. For a better risk management, more focus
      should be put on the distribution system security. Waterworks personnel should
      monitor the pressure regularly; reduce the leakage by upgrading the distribution
      network and use chlorination when conducting maintenance work.

PMID- 18816388
TI  - Alcohol use and misuse: what are the contributions of occupation and work
      organization conditions?
AB  - BACKGROUND: This research examines the specific contribution of occupation and
      work organization conditions to alcohol use and misuse. It is based on a social
      action model that takes into account agent personality, structures of daily life,
      and macro social structures. METHODS: Data come from a representative sample of
      10,155 workers in Quebec, Canada. Multinomial regression models corrected for
      sample design effect have been used to predict low-risk and high-risk drinking
      compared to non-drinkers. The contribution of occupation and work organization
      conditions (skill used, decision authority, physical and psychological demands,
      hours worked, irregular work schedule, harassment, unionization, job insecurity,
      performance pay, prestige) have been adjusted for family situation, social
      network outside the workplace, and individual characteristics. RESULTS: Compared
      to non-qualified blue-collars, both low-risk and high-risk drinking are
      associated with qualified blue-collars, semi-qualified white-collars, and middle
      managers; high-risk drinking is associated with upper managers. For constraints
      resources related to work organization conditions, only workplace harassment is
      an important determinant of both low-risk and high-risk drinking, but it is
      modestly moderated by occupation. Family situation, social support outside work,
      and personal characteristics of individuals are also associated with alcohol use
      and misuse. Non-work factors mediated/suppressed the role of occupation and work
      organization conditions. CONCLUSION: Occupation and workplace harassment are
      important factors associated with alcohol use and misuse. The results support the
      theoretical model conceptualizing alcohol use and misuse as being the product of
      stress caused by constraints and resources brought to bear simultaneously by
      agent personality, structures of daily life, and macro social structures.
      Occupational alcohol researchers must expand their theoretical perspectives to
      avoid erroneous conclusions about the specific role of the workplace.

PMID- 18816390
TI  - Negative exploration for pyloric stenosis--is it preventable?
AB  - BACKGROUND: The diagnosis of infantile hypertrophic pyloric stenosis (IHPS),
      although traditionally clinical, is now increasingly dependent on radiological
      corroboration. The rate of negative exploration in IHPS has been reported as 4%.
      The purpose of our study was to look at elements of supportive clinical evidence
      leading to positive diagnosis, and to review these with respect to misdiagnosed
      cases undergoing negative exploration. METHODS: All infants undergoing surgical
      exploration for IHPS between January 2000 and December 2004 were retrospectively
      analysed with regard to clinical symptoms, examination findings, investigations
      and operative findings. RESULTS: During the study period, 343 explorations were
      performed with a presumptive diagnosis of IHPS. Of these, 205 infants (60%) had a
      positive test feed, 269 (78%) had a positive ultrasound scan and 175 (55%) were
      alkalotic (pH >or=7.45 and/or base excess >or=2.5). The positive predictive value
      for an ultrasound (US) diagnosis was 99.1% for canal length >or=14 mm, and 98.7%
      for muscle thickness >or=4 mm. Four infants (1.1%) underwent a negative surgical
      exploration; Ultrasound was positive in 3, and negative in 1(who underwent
      surgery on the basis of a positive upper GI contrast). One US reported as
      positive had a muscle thickness <4 mm. Two false positive US were performed at
      peripheral hospitals. One infant had a false positive test feed following a
      positive ultrasound diagnosis. Two infants had negative test feeds. CONCLUSION: A
      1% rate of negative exploration in IHPS compares favourably with other studies.
      However potential causes of error were identified in all 4 cases. Confident
      diagnosis comprises a combination of positive test feed and an 'in house US' in
      an alkalotic infant. UGI contrast study should not be used in isolation to
      diagnose IHPS. If the test feed is negative, strict diagnostic measurements
      should be observed on US and the pyloric 'tumour' palpated on table under
      anaesthetic before exploration.

PMID- 18816389
TI  - Predicting protein linkages in bacteria: which method is best depends on task.
AB  - BACKGROUND: Applications of computational methods for predicting protein
      functional linkages are increasing. In recent years, several bacteria-specific
      methods for predicting linkages have been developed. The four major genomic
      context methods are: Gene cluster, Gene neighbor, Rosetta Stone, and Phylogenetic
      profiles. These methods have been shown to be powerful tools and this paper
      provides guidelines for when each method is appropriate by exploring different
      features of each method and potential improvements offered by their combination.
      We also review many previous treatments of these prediction methods, use the
      latest available annotations, and offer a number of new observations. RESULTS:
      Using Escherichia coli K12 and Bacillus subtilis, linkage predictions made by
      each of these methods were evaluated against three benchmarks: functional
      categories defined by COG and KEGG, known pathways listed in EcoCyc, and known
      operons listed in RegulonDB. Each evaluated method had strengths and weaknesses,
      with no one method dominating all aspects of predictive ability studied. For
      functional categories, as previous studies have shown, the Rosetta Stone method
      was individually best at detecting linkages and predicting functions among
      proteins with shared KEGG categories while the Phylogenetic profile method was
      best for linkage detection and function prediction among proteins with common COG
      functions. Differences in performance under COG versus KEGG may be attributable
      to the presence of paralogs. Better function prediction was observed when using a
      weighted combination of linkages based on reliability versus using a simple
      unweighted union of the linkage sets. For pathway reconstruction, 99 complete
      metabolic pathways in E. coli K12 (out of the 209 known, non-trivial pathways)
      and 193 pathways with 50% of their proteins were covered by linkages from at
      least one method. Gene neighbor was most effective individually on pathway
      reconstruction, with 48 complete pathways reconstructed. For operon prediction,
      Gene cluster predicted completely 59% of the known operons in E. coli K12 and 88%
      (333/418)in B. subtilis. Comparing two versions of the E. coli K12 operon
      database, many of the unannotated predictions in the earlier version were updated
      to true predictions in the later version. Using only linkages found by both Gene
      Cluster and Gene Neighbor improved the precision of operon predictions.
      Additionally, as previous studies have shown, combining features based on
      intergenic region and protein function improved the specificity of operon
      prediction. CONCLUSION: A common problem for computational methods is the
      generation of a large number of false positives that might be caused by an
      incomplete source of validation. By comparing two versions of a database, we
      demonstrated the dramatic differences on reported results. We used several
      benchmarks on which we have shown the comparative effectiveness of each
      prediction method, as well as provided guidelines as to which method is most
      appropriate for a given prediction task.

PMID- 18816391
TI  - Analysis of queries sent to PubMed at the point of care: observation of search
      behaviour in a medical teaching hospital.
AB  - BACKGROUND: The use of PubMed to answer daily medical care questions is limited
      because it is challenging to retrieve a small set of relevant articles and time
      is restricted. Knowing what aspects of queries are likely to retrieve relevant
      articles can increase the effectiveness of PubMed searches. The objectives of our
      study were to identify queries that are likely to retrieve relevant articles by
      relating PubMed search techniques and tools to the number of articles retrieved
      and the selection of articles for further reading. METHODS: This was a
      prospective observational study of queries regarding patient-related problems
      sent to PubMed by residents and internists in internal medicine working in an
      Academic Medical Centre. We analyzed queries, search results, query tools (Mesh,
      Limits, wildcards, operators), selection of abstract and full-text for further
      reading, using a portal that mimics PubMed. RESULTS: PubMed was used to solve
      1121 patient-related problems, resulting in 3205 distinct queries. Abstracts were
      viewed in 999 (31%) of these queries, and in 126 (39%) of 321 queries using query
      tools. The average term count per query was 2.5. Abstracts were selected in more
      than 40% of queries using four or five terms, increasing to 63% if the use of
      four or five terms yielded 2-161 articles. CONCLUSION: Queries sent to PubMed by
      physicians at our hospital during daily medical care contain fewer than three
      terms. Queries using four to five terms, retrieving less than 161 article titles,
      are most likely to result in abstract viewing. PubMed search tools are used
      infrequently by our population and are less effective than the use of four or
      five terms. Methods to facilitate the formulation of precise queries, using more
      relevant terms, should be the focus of education and research.

PMID- 18816392
TI  - Ultraconserved coding regions outside the homeobox of mammalian Hox genes.
AB  - BACKGROUND: All bilaterian animals share a general genetic framework that
      controls the formation of their body structures, although their forms are highly
      diversified. The Hox genes that encode transcription factors play a central role
      in this framework. All Hox proteins contain a highly conserved homeodomain
      encoded by the homeobox motif, but the other regions are generally assumed to be
      less conserved. In this study, we used comparative genomic methods to infer
      possible functional elements in the coding regions of mammalian Hox genes.
      RESULTS: We identified a set of ultraconserved coding regions (UCRs) outside the
      homeobox of mammalian Hox genes. Here a UCR is defined as a region of at least
      120 nucleotides without synonymous and nonsynonymous nucleotide substitutions
      among different orders of mammals. Further analysis has indicated that these UCRs
      occur only in placental mammals and they evolved apparently after the split of
      placental mammals from marsupials. Analysis of human SNP data suggests that these
      UCRs are maintained by strong purifying selection. CONCLUSION: Although mammalian
      genomes are known to contain ultraconserved non-coding elements (UNEs), this
      paper seems to be the first to report the UCRs in protein coding genes. The
      extremely high degree of sequence conservation in non-homeobox regions suggests
      that they might have important roles for the functions of Hox genes. We speculate
      that UCRs have some gene regulatory functions possibly in relation to the
      development of the intra-uterus child-bearing system.

PMID- 18816393
TI  - Non-steroidal anti-inflammatory drugs, Cyclooxygenase-2 inhibitors and
      paracetamol use in Queensland and in the whole of Australia.
AB  - BACKGROUND: Cross national drug utilization studies can provide information about
      different influences on physician prescribing. This is important for medicines
      with issues around safety and quality of use, like non selective non-steroidal
      anti-inflammatory drugs (ns-NSAIDs) and cyclo-oxygenase-2 (COX-2) inhibitors. To
      enable comparison of prescription medicine use across different jurisdictions
      with a range of population sizes, data first need to be compared within Australia
      to understand whether use in a smaller sub-population may be considered as
      representative of the total use within Australia. The aim of this study was to
      compare the utilization of non selective NSAID, COX-2 inhibitors and paracetamol
      between Queensland and Australia. METHOD: Dispensing data were obtained for
      concession beneficiaries for Australia for ns-NSAIDs, COX-2 inhibitors and
      paracetamol subsidized by the PBS over the period 1997-2003. The same data were
      purchased for Queensland. Data were converted to Defined Daily Dose (DDD)/1000
      beneficiaries/day (World Health Organization anatomical therapeutic chemical
      classification, 2005). RESULTS: Total NSAID and paracetamol consumption were
      similar in Australia and Queensland. Ns-NSAID use decreased sharply with the
      introduction of COX-2 inhibitors (from approximately 80 to 40 DDD/1000
      beneficiaries/day). Paracetamol was constant (approximately 45 DDD/1000
      beneficiaries/day). COX-2 inhibitors consumption was initially higher in
      Queensland than in the whole of Australia. CONCLUSION: Despite initial divergence
      in celecoxib use between Queensland and Australia, the use of ns-NSAIDs, COX-2
      inhibitors and paracetamol overall, in concession beneficiaries, was comparable
      in Australia and Queensland.

PMID- 18816394
TI  - Tuberculous meningitis presenting with unusual clinical features in Nigerians:
      Two case reports.
AB  - BACKGROUND: Tuberculous meningitis is common in developing countries and accounts
      for about 7.8% to 14% of all cases of tuberculosis in Nigeria. CASE PRESENTATION:
      Case 1 was a 17-year-old woman who presented with a 3-week history of weakness of
      the right upper and lower limbs, a 6-hour history of inability to speak and
      irrational behaviour. She had no remarkable past medical history. Physical
      examination revealed pyrexia (temperature of 38.2 degrees C) and altered level of
      consciousness (Glasgow coma score = 7/15). The signs of meningeal irritation were
      present and she had anisocoria and right spastic hemiparesis. Other aspects of
      physical examination were normal. Laboratory investigations showed an elevated
      erythrocyte sedimentation rate, normal cerebrospinal fluid protein and reduced
      glucose. The brain computed tomography scan showed features in keeping with
      obstructive hydrocephalus and she was immediately commenced on antituberculous
      drugs, intravenous steroids and mannitol. She made a remarkable clinical recovery
      and was discharged home 6 weeks after admission. Case 2 was a 40-year-old man who
      presented with a 6-week history of headache and fever and a 2-week history of
      alteration in level of consciousness. There was no history of neck pain and/or
      stiffness, nausea or vomiting. He had no other remarkable past medical history.
      He had been placed on various intravenous antibiotics in private hospitals before
      presentation, with no clinical improvement. Physical examination showed a young
      man in a coma (Glasgow coma score = 4/15) and febrile (temperature of 38.5
      degrees C) with signs of meningeal irritation. The brain stem reflexes were
      impaired and he had spastic quadriparesis. Further physical examination was
      essentially normal. The cerebrospinal fluid analysis showed features in keeping
      with meningeal inflammation and he had a raised erythrocyte sedimentation rate.
      The brain computed tomography scan showed features in keeping with obstructive
      hydrocephalus. He was placed on antituberculous drugs and intravenous steroids
      but despite this his clinical condition deteriorated and he died on the sixth day
      after admission. CONCLUSION: Late presentation of tuberculous meningitis is not
      rare in Nigerians and we report two cases of tuberculous meningitis that
      presented late to our health care facility. This report is intended to make
      clinicians aware of the unusual clinical presentations of tuberculous meningitis.

PMID- 18816395
TI  - A comparative analysis of metal transportomes from metabolically versatile
      Pseudomonas.
AB  - BACKGROUND: The availability of complete genome sequences of versatile
      Pseudomonas occupying remarkably diverse ecological niches enabled to gain
      insights into their adaptative assets. The objective of this study was to analyze
      the complete genetic repertoires of metal transporters (metal transportomes) from
      four representative Pseudomonas species and to identify metal transporters with
      "Genomic Island" associated features. METHODS: A comparative metal transporter
      inventory was built for the following four Pseudomonas species: P.putida (Ppu)
      KT2440, P.aeruginosa (Pae) PA01, P.fluorescens (Pfl) Pf-5 and P.syringae
      (Psy)pv.tomato DC3000 using TIGR-CMR and Transport DB. Genomic analysis of
      essential and toxic metal ion transporters was accomplished from the above
      inventory. Metal transporters with "Genomic Island" associated features were
      identified using Islandpath analysis. RESULTS: Dataset cataloguing has been
      executed for 262 metal transporters from the four spp. Additional metal ion
      transporters belonging to NiCoT, Ca P-type ATPase, Cu P-type ATPases, ZIP and
      MgtC families were identified. In Psy DC3000, 48% of metal transporters showed
      strong GI features while it was 45% in Ppu KT2440. In Pfl Pf-5 and Pae PA01 only
      26% of their metal transporters exhibited GI features. CONCLUSION: Our
      comparative inventory of 262 metal transporters from four versatile Pseudomonas
      spp is the complete suite of metal transportomes analysed till date in a
      prokaryotic genus. This study identified differences in the basic composition of
      metal transportomes from Pseudomonas occupying diverse ecological niches and also
      elucidated their novel features. Based on this inventory we analysed the role of
      horizontal gene transfer in expansion and variability of metal transporter
      families.

PMID- 18816396
TI  - Effort angina in a patient with advanced coronary artery disease. Role played by
      coronary angiography, Ivus and cardiac CT: case report.
AB  - Coronary angiography is considered to be the gold standard technique for
      assessing the severity of obstructive luminal narrowing; however, in a few
      circumstances it may be misleading. In these cases, cardiac computed tomography
      (CT) and intravascular ultrasound (IVUS) may help to give a correct
      interpretation.In this report, we describe the case of a 62-year-old man whose
      effort angina was first evaluated with coronary angiography, but whose severe
      stenosis of the right coronary artery was only observed on cardiac CT and IVUS.
      This additional diagnosis promptly resulted in a therapeutic approach with
      percutaneous transluminal coronary angioplasty (PTCA).

PMID- 18816397
TI  - Stability of methylnicotinate in aqueous solution as utilized in the 'niacin
      patch test'.
AB  - BACKGROUND: The topical application of methylnicotinate results in a localized
      vasodilatatory response which has been found to differ from that observed to
      occur in healthy controls in a variety of medical conditions. The stability of
      the drug in aqueous solution is unclear while difficulties can be encountered
      when preparing methylnicotinate solutions for this purpose. To aid in the
      determination of how long solutions of the drug should be stored before
      discarding we have used a collection of aged batches of methylnicotinate to
      determine the stability of the drug in aqueous solution. FINDINGS: The
      degradation of methylnicotinate was determined in batches which had been stored
      at 4 degrees C for between 5 and 1062 days prior to analysis by High Performance
      Liquid Chromatography. The major degradation product of methylnicotinate was
      nicotinic acid which formed at an approximate rate of 0.5% of the starting
      methylnicotinate concentration per annum. Furthermore, the ability of
      methylnicotinate solutions of different ages to induce vasodilatation was
      assessed in healthy volunteers. No significant difference in vasodilatatory
      response was apparent between batches which had been stored for between zero and
      1057 days. CONCLUSION: Methylnicotinate exhibits excellent chemical and
      biological stability in solution facilitating its use in clinical applications.

PMID- 18816398
TI  - Locally induced neural stem cells/pluripotent stem cells for in vivo cell
      replacement therapy.
AB  - Neural stem cells hold the key to innovative new treatments for age-associated
      degeneration and traumatic injury to the brain and spinal cord. We hypothesized
      that the in vivo induced pluripotent stem cells or neural stem cells through
      "forced gene expression" can be used to repair damaged brain areas or treat
      degenerative diseases. Hopefully, these in vivo patient-specific stem cells can
      bring a new avenue for cell replacement therapies.

PMID- 18816399
TI  - Evolution of the holozoan ribosome biogenesis regulon.
AB  - BACKGROUND: The ribosome biogenesis (RiBi) genes encode a highly-conserved
      eukaryotic set of nucleolar proteins involved in rRNA transcription, assembly,
      processing, and export from the nucleus. While the mode of regulation of this
      suite of genes has been studied in the yeast, Saccharomyces cerevisiae, how this
      gene set is coordinately regulated in the larger and more complex metazoan
      genomes is not understood. RESULTS: Here we present genome-wide analyses
      indicating that a distinct mode of RiBi regulation co-evolved with the E(CG)
      binding, Myc:Max bHLH heterodimer complex in a stem-holozoan, the ancestor of
      both Metazoa and Choanoflagellata, the protozoan group most closely related to
      animals. These results show that this mode of regulation, characterized by an
      E(CG)-bearing core-promoter, is specific to almost all of the known genes
      involved in ribosome biogenesis in these genomes. Interestingly, this holozoan
      RiBi promoter signature is absent in nematode genomes, which have not only
      secondarily lost Myc but are marked by invariant cell lineages typically
      producing small body plans of 1000 somatic cells. Furthermore, a detailed
      analysis of 10 fungal genomes shows that this holozoan signature in RiBi genes is
      not found in hemiascomycete fungi, which evolved their own unique regulatory
      signature for the RiBi regulon. CONCLUSION: These results indicate that a Myc
      regulon, which is activated in proliferating cells during normal development as
      well as during tumor progression, has primordial roots in the evolution of an
      inducible growth regime in a protozoan ancestor of animals. Furthermore, by
      comparing divergent bHLH repertoires, we conclude that regulation by Myc but not
      by other bHLH genes is responsible for the evolutionary maintenance of E(CG)
      sites across the RiBi suite of genes.

PMID- 18816400
TI  - Robotic assisted laparoscopic partial nephrectomy for suspected renal cell
      carcinoma: retrospective review of surgical outcomes of 35 cases.
AB  - BACKGROUND: A standard of care for the treatment of small renal masses is partial
      nephrectomy. The open and laparoscopic approaches have been well described in the
      literature. Robotic assistance may augment partial nephrectomy by aiding in
      dissection and renal reconstruction. In this communication we describe the
      surgical outcomes of 35 patients undergoing robotic partial nephrectomy. METHODS:
      Patient records and databases were reviewed for 35 consecutive patients
      undergoing RPN. Clinical, pathological, and radiographic data were obtained. The
      data was deidentified. RESULTS: Thirty five patients successfully underwent RPN.
      An additional 2 patients were converted to other nephron sparing procedures. Mean
      tumor size was 2.8 cm, and mean OR time was 142 minutes. Mean warm ischemia time
      was 20 minutes. All margins were negative. There were 4 complications, and no
      patients required reoperation. CONCLUSION: Robotic partial nephrectomy can
      produce excellent initial results. Further studies should be performed to compare
      the outcomes to laparoscopic and open operations.

PMID- 18816401
TI  - Dynamic activation of bone morphogenetic protein signaling in collagen-induced
      arthritis supports their role in joint homeostasis and disease.
AB  - INTRODUCTION: Rheumatoid arthritis is a chronic systemic autoimmune disease
      affecting peripheral joints and leading to loss of joint function. The severity
      and outcome of disease are dependent on the balance between
      inflammatory/destructive and homeostatic or repair pathways. Increasing evidence
      suggests a role for bone morphogenetic protein (BMP) signaling in joint
      homeostasis and disease. METHODS: Activation of BMP signaling in collagen-induced
      arthritis as a model of rheumatoid arthritis was studied by immunohistochemistry
      and Western blot for phosphorylated SMAD1/5 at different time points. Expression
      of different BMP ligands and noggin, a BMP antagonist, was determined on synovium
      and cartilage extracts of arthritic knees, at different time points, with
      quantitative polymerase chain reaction. At the protein level, BMP2 and BMP7 were
      studied with immunohistochemistry. Finally, the effect of anti-tumor necrosis
      factor-alpha (TNFalpha) treatment on the expression of BMP2, BMP7, and growth and
      differentiation factor-5 (GDF5) in synovium and cartilage of arthritic knees was
      investigated. RESULTS: A time-dependent activation of the BMP signaling pathway
      in collagen-induced arthritis was demonstrated with a dynamic and characteristic
      expression pattern of different BMP subfamily members in synovium and cartilage
      of arthritic knees. As severity increases, the activation of BMP signaling
      becomes more prominent in the invasive pannus tissue. BMP2 is present in
      cartilage and the hyperplastic lining layer. BMP7 is found in the sublining zone
      and inflammatory infiltrate. Treatment with etanercept slowed down progression of
      disease, but no change in expression of GDF5, BMP2, and BMP7 in synovium was
      found; in the cartilage, however, blocking of TNFalpha increased the expression
      of BMP7. CONCLUSIONS: BMP signaling is dynamically activated in collagen-induced
      arthritis and is partly TNFalpha-independent. TNFalpha blocking increased the
      expression of BMP7 in the articular cartilage, possibly enhancing anabolic
      mechanisms. Different types of source and target cells are recognized. These data
      further support a role for BMP signaling in arthritis.

PMID- 18816402
TI  - Fatigue testing of three peristernal median sternotomy closure techniques.
AB  - BACKGROUND: Failure of a sternotomy closure because of closure system fatigue is
      a complication that may result in dehiscence and put the individual at risk for
      serious complications. The purpose of this study was to assess the fatigue
      performance of three peristernal median sternotomy closure techniques (figure-of
      eight stainless-steel wires, figure-of-eight stainless-steel cables, or Pectofix
      Dynamic Sternal Fixation [DSF] stainless-steel plates) in order to quantify the
      potential risk of fatigue failure of these devices when subject to cyclic loads
      in physiologically relevant loading directions. STUDY DESIGN: All tests were
      conducted on polyurethane foam sternal models. A cardiothoracic surgeon divided
      each sternal model longitudinally and repaired it with a closure device. Tests
      were performed using a materials testing system that applied cyclic loading in a
      uniaxial direction until the test model catastrophically broke or data run-out
      occurred. For each loading direction (lateral distraction and longitudinal
      shear), five trials of each closure technique were tested. Life data and location
      of device failure (if present) were evaluated. Statistical analysis was performed
      using regression with life data allowed for correlation between life data and the
      various closure techniques to develop risk assessment curves for each device.
      RESULTS: The data show that the figure-of-eight stainless-steel cable and the DSF
      plate systems are considerably less likely to fail under both lateral distraction
      and longitudinal shear cyclic loading conditions as compared to the figure-of
      eight stainless-steel wire system. Moreover, the figure-of-eight stainless-steel
      cable system is the most resistant to failure, particularly for high cycle
      counts. CONCLUSION: This study in addition to Cohen and Griffin's earlier
      published biomechanical comparison of the ultimate strength of these same three
      closure techniques provide extensive experimental evidence regarding the
      mechanical differences among these three peristernal median sternotomy closure
      techniques. All data support the hypothesis that both the DSF plate system and
      the stainless-steel cable system offer important advantages over figure-of-eight
      wire closure techniques; although twisted wires are the weak-link in the systems
      we tested.

PMID- 18816403
TI  - Could lymphatic mapping and sentinel node biopsy provide oncological providence
      for local resectional techniques for colon cancer? A review of the literature.
AB  - BACKGROUND: Endoscopic resectional techniques for colon cancer are undermined by
      their inability to determine lymph node status. This limits their application to
      only those lesions at the most minimal risk of lymphatic dissemination whereas
      their technical capacity could allow intraluminal or even transluminal address of
      larger lesions. Sentinel node biopsy may theoretically address this breach
      although the variability of its reported results for this disease is worrisome.
      METHODS: Medline, EMBASE and Cochrane databases were interrogated back to 1999 to
      identify all publications concerning lymphatic mapping for colon cancer with
      reference cross-checking for completeness. All reports were examined from the
      perspective of in vivo technique accuracy selectively in early stage disease
      (i.e. lesions potentially within the technical capacity of endoscopic resection).
      RESULTS: Fifty-two studies detailing the experiences of 3390 patients were
      identified. Considerable variation in patient characteristics as well as in
      surgical and histological quality assurances were however evident among the
      studies identified. In addition, considerable contamination of the studies by
      inclusion of rectal cancer without subgroup separation was frequent. Indeed such
      is the heterogeneity of the publications to date, formal meta-analysis to pool
      patient cohorts in order to definitively ascertain technique accuracy in those
      with T1 and/or T2 cancer is not possible. Although lymphatic mapping in early
      stage neoplasia alone has rarely been specifically studied, those studies that
      included examination of false negative rates identified high T3/4 patient
      proportions and larger tumor size as being important confounders. Under selected
      circumstances however the technique seems to perform sufficiently reliably to
      allow it prompt consideration of its use to tailor operative extent. CONCLUSION:
      The specific question of whether sentinel node biopsy can augment the oncological
      propriety for endoscopic resective techniques (including Natural Orifice
      Transluminal Endoscopic Surgery [NOTES]) cannot be definitively answered at
      present. Study heterogeneity may account for the variability evident in the
      results from different centers. Enhanced capacity (perhaps to the level necessary
      to consider selective avoidance of en bloc mesenteric resection) by its
      confinement to only early stage disease is plausible although not proven.
      Specific study of the technique in early stage tumors is clearly essential before
      proffering this approach.

PMID- 18816404
TI  - Identification and analysis of evolutionary selection pressures acting at the
      molecular level in five forkhead subfamilies.
AB  - BACKGROUND: Members of the forkhead gene family act as transcription regulators
      in biological processes including development and metabolism. The evolution of
      forkhead genes has not been widely examined and selection pressures at the
      molecular level influencing subfamily evolution and differentiation have not been
      explored. Here, in silico methods were used to examine selection pressures acting
      on the coding sequence of five multi-species FOX protein subfamily clusters;
      FoxA, FoxD, FoxI, FoxO and FoxP. RESULTS: Application of site models, which
      estimate overall selection pressures on individual codons throughout the
      phylogeny, showed that the amino acid changes observed were either neutral or
      under negative selection. Branch-site models, which allow estimated selection
      pressures along specified lineages to vary as compared to the remaining
      phylogeny, identified positive selection along branches leading to the FoxA3 and
      Protostomia clades in the FoxA cluster and the branch leading to the FoxO3 clade
      in the FoxO cluster. Residues that may differentiate paralogs were identified in
      the FoxA and FoxO clusters and residues that differentiate orthologs were
      identified in the FoxA cluster. Neutral amino acid changes were identified in the
      forkhead domain of the FoxA, FoxD and FoxP clusters while positive selection was
      identified in the forkhead domain of the Protostomia lineage of the FoxA cluster.
      A series of residues under strong negative selection adjacent to the N- and C
      termini of the forkhead domain were identified in all clusters analyzed
      suggesting a new method for refinement of domain boundaries. Extrapolation of
      domains among cluster members in conjunction with selection pressure information
      allowed prediction of residue function in the FoxA, FoxO and FoxP clusters and
      exclusion of known domain function in residues of the FoxA and FoxI clusters.
      CONCLUSION: Consideration of selection pressures observed in conjunction with
      known functional information allowed prediction of residue function and
      refinement of domain boundaries. Identification of residues that differentiate
      orthologs and paralogs provided insight into the development and functional
      consequences of paralogs and forkhead subfamily composition differences among
      species. Overall we found that after gene duplication of forkhead family members,
      rapid differentiation and subsequent fixation of amino acid changes through
      negative selection has occurred.

PMID- 18816405
TI  - Gene expression profiling of liver from dairy cows treated intra-mammary with
      lipopolysaccharide.
AB  - BACKGROUND: Liver plays a profound role in the acute phase response (APR)
      observed in the early phase of acute bovine mastitis caused by Escherichia coli
      (E. coli). To gain an insight into the genes and pathways involved in hepatic APR
      of dairy cows we performed a global gene expression analysis of liver tissue
      sampled at different time points before and after intra-mammary (IM) exposure to
      E. coli lipopolysaccharide (LPS) treatment. RESULTS: Approximately 20% target
      transcripts were differentially expressed and eight co-expression clusters were
      identified. Each cluster had a unique time-dependent expression profile and
      consisted of genes involved in different biological processes. Our findings
      suggest that APR in the liver is triggered by the activation of signaling
      pathways that are involved with common and hepatic-specific transcription factors
      and pro-inflammatory cytokines. These mediators in turn stimulated or repressed
      the expression of genes encoding acute phase proteins (APP), collectins,
      complement components, chemokines, cell adhesion molecules and key metabolic
      enzymes during the APR. Hormones, anti-inflammatory and other hypothalamus
      pituitary-adrenal axis (HPAA) linked mediators also seemed to participate in APR.
      CONCLUSION: Performing global gene expression analysis on liver tissue from IM
      LPS treated cows verified that the liver plays a major role in the APR of E. coli
      mastitis, and that the bovine hepatic APR follows the same pattern as other
      mammals when they are challenged with LPS. Our work presents the first insight
      into the dynamic changes in gene expression in the liver that influences the
      induction, kinetics and clinical outcome of the APR in dairy cows.

PMID- 18816406
TI  - Tracheal diverticulum in an asymptomatic male: a case report.
AB  - INTRODUCTION: An air filled lesion can be a diagnostic dilemma and a careful
      investigation must be following to clarity any underlining pathology. CASE
      PRESENTATION: A 62-year old male, ex smoker, with a history of chronic cough was
      examined with helical CT tomography and an air filled lesion was demonstrated at
      the right paratracheal region at the thoracic inlet. A narrow connection to
      trachea lumen was also visible, a critical element to establish the diagnosis of
      ttracheal diverticulosis. CONCLUSION: This malformation is a rare anomaly with
      two types, the congenital and the acquired one. It must be included into the
      differential diagnosis of any air filled lesion at the thoracic inlet. Computed
      tomography scans (with thin section and reconstructed images) seem the proper
      imagine. Bronchoscopy can also visualize the diverticulum although sometimes the
      connection with trachea can't be detected. In most cases is asymptomatic and
      needs no special treatment. A possible danger of repeated respiratory infections
      and insufficient intubation and/or ventilation must be in mind.

PMID- 18816407
TI  - Sister Mary Joseph's nodule: Three case reports.
AB  - BACKGROUND: An umbilical metastatic lesion is called 'Sister Mary Joseph's
      nodule'. It is an uncommon clinical or radiographic finding, and it is rare as
      the first sign of a malignant disease. CASE PRESENTATION: We report three cases
      of Sister Mary Joseph's nodule. In the three cases presented, the primary tumor
      was an adenocarcinona of the sigmoid colon, a carcinoma of the bladder, and an
      adenocarcinoma of the gallbladder, respectively. CONCLUSION: The differential
      diagnosis of an umbilical lesion should always include metastatic disease apart
      from benign lesions and primary neoplasms.

PMID- 18816408
TI  - Modifying the DPClus algorithm for identifying protein complexes based on new
      topological structures.
AB  - BACKGROUND: Identification of protein complexes is crucial for understanding
      principles of cellular organization and functions. As the size of protein-protein
      interaction set increases, a general trend is to represent the interactions as a
      network and to develop effective algorithms to detect significant complexes in
      such networks. RESULTS: Based on the study of known complexes in protein
      networks, this paper proposes a new topological structure for protein complexes,
      which is a combination of subgraph diameter (or average vertex distance) and
      subgraph density. Following the approach of that of the previously proposed
      clustering algorithm DPClus which expands clusters starting from seeded vertices,
      we present a clustering algorithm IPCA based on the new topological structure for
      identifying complexes in large protein interaction networks. The algorithm IPCA
      is applied to the protein interaction network of Sacchromyces cerevisiae and
      identifies many well known complexes. Experimental results show that the
      algorithm IPCA recalls more known complexes than previously proposed clustering
      algorithms, including DPClus, CFinder, LCMA, MCODE, RNSC and STM. CONCLUSION: The
      proposed algorithm based on the new topological structure makes it possible to
      identify dense subgraphs in protein interaction networks, many of which
      correspond to known protein complexes. The algorithm is robust to the known high
      rate of false positives and false negatives in data from high-throughout
      interaction techniques. The program is available at
      http://netlab.csu.edu.cn/bioinformatics/limin/IPCA.

PMID- 18816409
TI  - Empyema associated with community-acquired pneumonia: a Pediatric Investigator's
      Collaborative Network on Infections in Canada (PICNIC) study.
AB  - BACKGROUND: Although the incidence of serious morbidity with childhood pneumonia
      has decreased over time, empyema as a complication of community-acquired
      pneumonia continues to be an important clinical problem. We reviewed the
      epidemiology and clinical management of empyema at 8 pediatric hospitals in a
      period before the widespread implementation of universal infant heptavalent
      pneumococcal vaccine programs in Canada. METHODS: Health records for children<18
      years admitted from 1/1/00-31/12/03 were searched for ICD-9 code 510 or ICD-10
      code J869 (Empyema). Empyema was defined as at least one of: thoracentesis with
      microbial growth from pleural fluid, or no pleural fluid growth but compatible
      chemistry or cell count, or radiologist diagnosis, or diagnosis at surgery.
      Patients with empyemas secondary to chest trauma, thoracic surgery or esophageal
      rupture were excluded. Data was retrieved using a standard form with a data
      dictionary. RESULTS: 251 children met inclusion criteria; 51.4% were male. Most
      children were previously healthy and those<or=5 years of age comprised 57% of the
      cases. The median length of hospitalization was 9 days. Admissions occurred in
      all months but peaked in winter. Oxygen supplementation was required in 77% of
      children, 75% had chest tube placement and 33% were admitted to an intensive care
      unit. While similarity in use of pain medication, antipyretics and antimicrobial
      use was observed, a wide variation in number of chest radiographs and invasive
      procedures (thoracentesis, placement of chest tubes) was observed between
      centers. The most common organism found in normally sterile samples (blood,
      pleural fluid, lung biopsy) was Streptococcus pneumoniae. CONCLUSION: Empyema
      occurs most commonly in children under five years and is associated with
      considerable morbidity. Variation in management by center was observed. Enhanced
      surveillance using molecular methods could improve diagnosis and public health
      planning, particularly with regard to the relationship between immunization
      programs and the epidemiology of empyema associated with community-acquired
      pneumonia in children.

PMID- 18816410
TI  - Efficient inhibition of murine breast cancer growth and metastasis by gene
      transferred mouse survivin Thr34-->Ala mutant.
AB  - BACKGROUND: Metastasis in breast cancer is a vital concern in treatment because
      most women with primary breast cancer have micrometastases to distant sites at
      diagnosis. As a member of the inhibitor of apoptosis protein (IAP) family,
      survivin has been proposed as an attractive target for new anticancer
      interventions. In this study, we investigated the role of the plasmid encoding
      the phosphorylation-defective mouse survivin threonine 34-->alanine mutant
      (Msurvivin T34A plasmid) in suppressing both murine primary breast carcinomas and
      pulmonary metastases. METHODS: In vitro study, induction of apoptosis by
      Msurvivin T34A plasmid complexed with cationic liposome (DOTAP/Chol) was examined
      by PI staining fluorescence microscopy and flow cytometric analysis. The anti
      tumor and anti-metastases activity of Msurvivin T34A plasmid complexed with
      cationic liposome (DOTAP/Chol) was evaluated in female BALB/c mice bearing 4T1
      s.c. tumors. Mice were treated twice weekly with i.v. administration of Msurvivin
      T34A plasmid complexed with cationic liposome (DOTAP/Chol), PORF-9 null plasmid
      complexed with cationic liposome (DOTAP/Chol), 0.9% NaCl solution for 4 weeks.
      Tumor volume was observed. After sacrificed, tumor net weight was measured and
      Lung metastatic nodules of each group were counted. Assessment of apoptotic cells
      by TUNEL assay was conducted in tumor tissue. Microvessel density within tumor
      tissue was determined by CD31 immunohistochemistry. Alginate-encapsulated tumor
      cells test was conducted to evaluate the effect on angiogenesis. By experiment of
      cytotoxicity T lymphocytes, we test whether Msurvivin T34A plasmid complexed with
      cationic liposome (DOTAP/Chol) can induce specific cell immune response. RESULTS:
      Administration of Msurvivin T34A plasmid complexed with cationic liposome
      (DOTAP/Chol) resulted in significant inhibition in the growth and metastases of
      4T1 tumor model. These anti-tumor and anti-metastases responses were associated
      with triggering the apoptosis of tumor cells directly, inhibiting angiogenesis
      and inducing specific cellular immune response. CONCLUSION: The present findings
      suggest that the Msurvivin T34A plasmid complexed with cationic liposome may
      provide an effective approach to inhibit the growth and metastases of a highly
      metastatic mouse breast cancer model with minimal side effects.

PMID- 18816411
TI  - Attitudes towards those bereaved by a suicide: a population-based, cross
      sectional study in rural Japan.
AB  - BACKGROUND: Family or friends bereaved by suicide are at risk of experiencing
      complications because of attitudes regarding suicide. It is important that
      individuals close to those grieving after a death by suicide demonstrate adequate
      knowledge and compassionate attitudes. To this end, we examined the factors that
      contribute to attitudes toward persons bereaved by the suicide of a family member
      or friend, and perceptions of suicide prevention and the promotion of mental
      health. METHODS: A total of 5154 residents of a rural town in northern Japan aged
      30-69 years completed a cross-sectional questionnaire. The questionnaire gathered
      data about demographic variables, depressive symptoms, and issues related to
      suicide including personal experience of an acquaintance's suicide, attitudes
      towards those bereaved by suicide, and perceptions regarding suicide prevention.
      Factors related to these attitudes and perceptions were analysed using logistic
      regression models. RESULTS: Overall, 67.5% of respondents demonstrated
      appropriate attitudes towards those bereaved by suicide; 30.4% of responses were
      undetermined, and 2.1% were inappropriate. Undetermined attitudes were associated
      with male gender (adjusted OR 1.42, 95%CI = 1.26-1.61), younger age (2.64, 2.12
      3.29), lower education level (1.32, 1.07-1.62), greater severity of depression
      (3.81, 2.80-5.20), and lack of personal experience of an acquaintance's suicide
      (1.39, 1.22-1.57). Inappropriate attitudes were associated with male gender
      (adjusted OR 1.98, 95%CI = 1.33-2.94), lower education level (2.55 1.34-4.83),
      and greater severity of depression (6.93, 3.52-13.67). Overall, 16.0%
      demonstrated passive thoughts regarding suicide prevention and the promotion of
      mental health in the community, and were associated with male gender (1.22, 1.04
      1.42), younger age (2.72, 2.03-3.65), lower education level (1.32, 1.02-1.71),
      and greater severity of depression (4.94, 3.58-6.82). CONCLUSION: Factors that
      contributed to undetermined attitudes included male gender, younger age, lower
      education level, greater severity of depression, and lack of personal experience
      of an acquaintance's suicide. Passive thoughts regarding suicide prevention and
      the promotion of mental health were associated with male gender, younger age,
      lower education level, and greater severity of depression.

PMID- 18816412
TI  - Bordetella pertussis isolates in Finland: serotype and fimbrial expression.
AB  - BACKGROUND: Bordetella pertussis causes whooping cough or pertussis in humans. It
      produces several virulence factors, of which the fimbriae are considered adhesins
      and elicit immune responses in the host. B. pertussis has three distinct
      serotypes Fim2, Fim3 or Fim2,3. Generally, B. pertussis Fim2 strains predominate
      in unvaccinated populations, whereas Fim3 strains are often isolated in
      vaccinated populations. In Finland, pertussis vaccination was introduced in 1952.
      The whole-cell vaccine contained two strains, 18530 (Fim3) since 1962 and strain
      1772 (Fim2,3) added in 1976. After that the vaccine has remained the same until
      2005 when the whole-cell vaccine was replaced by the acellular vaccine containing
      pertussis toxin and filamentous hemagglutinin. Our aims were to study serotypes
      of Finnish B. pertussis isolates from 1974 to 2006 in a population with > 90%
      vaccination coverage and fimbrial expression of the isolates during infection.
      Serotyping was done by agglutination and serotype-specific antibody responses
      were determined by blocking ELISA. RESULTS: Altogether, 1,109 isolates were
      serotyped. Before 1976, serotype distributions of Fim2, Fim3 and Fim2,3 were 67%,
      19% and 10%, respectively. From 1976 to 1998, 94% of the isolates were Fim2
      serotype. Since 1999, the frequency of Fim3 strains started to increase and
      reached 83% during a nationwide epidemic in 2003. A significant increase in level
      of serum IgG antibodies against purified fimbriae was observed between paired
      sera of 37 patients. The patients infected by Fim3 strains had antibodies which
      blocked the binding of monoclonal antibodies to Fim3 but not to Fim2. Moreover,
      about one third of the Fim2 strain infected patients developed antibodies capable
      of blocking of binding of both anti-Fim2 and Fim3 monoclonal antibodies.
      CONCLUSION: Despite extensive vaccinations in Finland, B. pertussis Fim2 strains
      were the most common serotype. Emergence of Fim3 strains started in 1999 and
      coincided with nationwide epidemics. Results of serotype-specific antibody
      responses suggest that Fim2 strains could express Fim3 during infection, showing
      a difference in fimbrial expression between in vivo and in vitro.

PMID- 18816413
TI  - Patients' perception and actual practice of informed consent, privacy and
      confidentiality in general medical outpatient departments of two tertiary care
      hospitals of Lahore.
AB  - BACKGROUND: The principles of informed consent, confidentiality and privacy are
      often neglected during patient care in developing countries. We assessed the
      degree to which doctors in Lahore adhere to these principles during outpatient
      consultations. MATERIAL & METHOD: The study was conducted at medical out-patient
      departments (OPDs) of two tertiary care hospitals (one public and one private
      hospital) of Lahore, selected using multi-stage sampling. 93 patients were
      selected from each hospital. Doctors' adherence to the principles of informed
      consent, privacy and confidentiality was observed through client flow analysis
      performed by trained personnel. Overall patient perception was also assessed
      regarding these practices and was compared with the assessment made by our data
      collectors. RESULTS: Some degree of informed consent was obtained from only 9.7%
      patients in the public hospital and 47.8% in the private hospital. 81.4% of
      patients in the public hospital and 88.4% in the private hospital were accorded
      at least some degree of privacy. Complete informational confidentiality was
      maintained only in 10.8% and 35.5% of cases in public & private hospitals
      respectively. Informed consent and confidentiality were better practiced in the
      private compared to the public hospital (two-sample t-test > 2, p value < 0.05).
      There was marked disparity between the patients' perspective of these ethical
      practices and the assessment of our trained data collectors. CONCLUSION:
      Observance of medical ethics is inadequate in hospitals of Lahore. Doctors should
      be imparted formal training in medical ethics and national legislation on medical
      ethics is needed. Patients should be made aware of their rights to medical
      ethics.

PMID- 18816414
TI  - Abrasions and lameness in piglets born in different farrowing systems with
      different types of floor.
AB  - BACKGROUND: The quality of the floor is essential to the welfare of piglets as
      abrasions often are recorded in newborn piglets, and such lesions may lead to
      lameness. Apart from animal suffering, lameness contributes to losses in form of
      dead piglets, decreased growth, and increased use of antibiotics and manual
      labour. METHODS: In a herd with three different farrowing systems, 37 litters
      (390 piglets) were studied until the age of 3 weeks with respect to presence of
      skin wounds and abrasions. Lameness was registered until the age of 7 weeks.
      Eight lame piglets were sacrificed before medical treatment and subjected to
      necropsy including histopathological and microbiological examinations. Isolates
      of streptococci, staphylococci and E. coli were tested with respect to
      antimicrobial resistance. Mastitis was observed in ten sows. RESULTS: The most
      severe abrasions at carpus and soles were seen in the system with a new solid
      concrete floor with a slatted floor over the dunging area. The lowest magnitude
      was observed in the deep litter system with peat. Sole bruising was more common
      in the systems with concrete floor compared to the deep litter system with peat,
      and the differce in prevalence was significant at all examination days. The
      lesions decreased with time and about 75% of the treatments for lameness were
      performed during the first three weeks of life. The overall prevalence of
      lameness was highest in the system with new solid concrete floor with a slatted
      floor over the dunging area (9.4%) followed by the old solid concrete floor
      (7.5%). A lower (p < 0.05) prevalence was seen in the deep litters system with
      peat (3.3%). No significant relationship between mastitis and abrasions or
      lameness in the offspring was observed. CONCLUSION: There were large differences
      in the prevalence of abrasions and lameness between the floor types. The deep
      litter system with peat provided a soft and good floor for piglets. The overall
      prevalence of lameness was only diagnosed in every fourth litter in that system
      compared to in every second litter in the systems with concrete floor. In
      contrast, the incidence of mastitis in the sows during the first week after
      farrowing was higher than in the systems with concrete floor.

PMID- 18816415
TI  - Investigating the effects of climate variations on bacillary dysentery incidence
      in northeast China using ridge regression and hierarchical cluster analysis.
AB  - BACKGROUND: The effects of climate variations on bacillary dysentery incidence
      have gained more recent concern. However, the multi-collinearity among
      meteorological factors affects the accuracy of correlation with bacillary
      dysentery incidence. METHODS: As a remedy, a modified method to combine ridge
      regression and hierarchical cluster analysis was proposed for investigating the
      effects of climate variations on bacillary dysentery incidence in northeast
      China. RESULTS: All weather indicators, temperatures, precipitation, evaporation
      and relative humidity have shown positive correlation with the monthly incidence
      of bacillary dysentery, while air pressure had a negative correlation with the
      incidence. Ridge regression and hierarchical cluster analysis showed that during
      1987-1996, relative humidity, temperatures and air pressure affected the
      transmission of the bacillary dysentery. During this period, all meteorological
      factors were divided into three categories. Relative humidity and precipitation
      belonged to one class, temperature indexes and evaporation belonged to another
      class, and air pressure was the third class. CONCLUSION: Meteorological factors
      have affected the transmission of bacillary dysentery in northeast China.
      Bacillary dysentery prevention and control would benefit from by giving more
      consideration to local climate variations.

PMID- 18816416
TI  - Medico-legal reasoning in disability assessment: a focus group and validation
      study.
AB  - BACKGROUND: Decisions on disability pensions are based, among others, on medical
      reports. The way these medical assessments are performed is largely unclear. The
      aim of the study was to determine which grounds are used by social insurance
      physicians (SIPs) in these assessments and to determine if the identification of
      these grounds can help improve the quality of assessments in social insurance
      practice. The article describes a focus group study and a questionnaire study
      with SIPs in four different countries. METHOD: Using focus group discussions of
      SIPs discussing the same case in Belgium, the Netherlands, Norway and Slovenia (N
      = 29) we determined the arguments and underlying grounds as used by the SIP's. We
      used a questionnaire study among other SIPs (N = 60) in the same countries to
      establish a first validation of these grounds. RESULTS: Grounds in the focus
      groups were comparable between the countries studied. The grounds were also
      recognized by SIPs who had not participated in the focus groups. SIPs agreed most
      on grounds with regard to the claimant's health condition, and about the
      claimant's duty to explore rehabilitation and work resumption, but less on
      accepting permanent incapacity when all options for treatment were exhausted.
      CONCLUSION: Grounds that SIPs use refer to a limited group of key elements of
      disability evaluation. SIPs interpret disability in social insurance according to
      the handicapped role and strive at making their evaluation fair trials. ICF is
      relevant with regard to the health condition and to the process of evaluation.
      Identification of grounds is a valuable instrument for controlling the quality of
      disability evaluation. The grounds also appear to be internationally comparable
      which may enhance scientific study in this area.

PMID- 18816417
TI  - Upregulation of CD94 on CD8+T cells in anterior chamber-associated immune
      deviation.
AB  - BACKGROUND: CD8+ regulatory T cells (Treg) have been considered to be involved in
      a model of ocular-induced tolerance, known as anterior chamber-associated immune
      deviation (ACAID). The phenotype and characteristics of CD8+Treg in ACAID remain
      only poorly understood. Recent studies have reported that the CD94-Qa-1 system is
      implicated in the induction of ACAID CD8+Treg, but the functions and
      characteristics of CD8+CD94+T cells remain unclear. RESULTS: Both mRNA and
      protein of CD94 and NKG2A were markedly up-regulated on splenic CD8+T cells of
      ACAID mice compared with controls. Flow cytometric analysis showed that very few
      CD8+CD94+T cells express granzyme B, perforin and Foxp3. CD8+CD94+T cells, but
      not CD8+CD94-T cells, magnetically isolated from the spleens of ACAID mice,
      produced large amounts of TGF-beta1 and exhibited suppressive activity in vitro.
      Neutralization of TGF-beta1 caused reversal of suppression mediated by CD8+CD94+T
      cells. CONCLUSION: CD8+CD94+T cells from ACAID mice exhibited suppressive
      activity in association with enhanced expression of TGF-beta1, suggesting that
      CD8+Treg are mainly distributed in CD94+T cell subpopulations.

PMID- 18816418
TI  - Measuring care of the elderly: psychometric testing and modification of the Time
      in Care instrument for measurement of care needs in nursing homes.
AB  - BACKGROUND: Aging entails not only a decrease in the ability to be active, but
      also a trend toward increased dependence to sustain basic life functions. An
      important aspect for appropriately elucidating the individual's care needs is the
      ability to measure them both simply and reliably. Since 2006 a new version of the
      Time in Care needs (TIC-n) instrument (19-item version) has been explored and
      used in one additional municipality with the same structure as the one described
      in an earlier study. METHODS: The TIC-n assessment was conducted on a total of
      1282 care recipients. Factor analysis (principal component) was applied to
      explore the construct validity of the TIC-n. Cronbach's alpha was calculated to
      test reliability and for each of the items remaining in the instrument after
      factor analysis, an inter-rater comparison was carried out on all recipients in
      both municipalities. Independently of each other, a weighted Kappa (Kw) was
      calculated. Results. The mean of each weighted Kappa (Kw) for the dimensions in
      the two municipalities was 0.75 and 0.76, respectively. Factor analysis showed
      that all 19 items had a factor loading of >or=0.40. Three factors (General Care,
      Medical Care and Cognitive Care) were created. CONCLUSION: The TIC-n instrument
      has now been tested for validity and reliability in two municipalities with
      satisfactory results. However, TIC-n can not yet be used as a golden standard,
      but it can be recommended for use of measurement of individual care needs in
      municipal elderly care.

PMID- 18816419
TI  - Cochlear prostheses: L'enfant terrible of auditory rehabilitation.

PMID- 18816420
TI  - Cochlear implants and hearing aids: some personal and professional reflections.

PMID- 18816421
TI  - Personal reflections on the multichannel cochlear implant and a view of the
      future.
AB  - The multichannel cochlear implant is the first neural prosthesis to effectively
      and safely bring electronic technology into a direct physiological relation with
      the central nervous system and human consciousness. It is also the first cochlear
      implant to give speech understanding to tens of thousands of persons with
      profound deafness and spoken language to children born deaf in more than 80
      countries. In so doing, it is the first major advance in research and technology
      to help deaf children communicate since Sign Language of the Deaf was developed
      at the Paris deaf school (L'Institut National de Jeunes Sourds de Paris) >200
      years ago. Furthermore, biomedical research has been fundamental for ensuring
      that the multielectrode implant is safe as well as effective. More recent
      research has also shown that bilateral implants confer the benefits of binaural
      hearing. Future research using nanotechnology should see high-fidelity sound
      received, which would help deaf persons communicate in noise and enjoy music.
      Research should also lead to implants in ears with useful hearing.

PMID- 18816422
TI  - Cochlear implants: current designs and future possibilities.
AB  - The cochlear implant is the most successful of all neural prostheses developed to
      date. It is the most effective prosthesis in terms of restoration of function,
      and the people who have received a cochlear implant outnumber the recipients of
      other types of neural prostheses by orders of magnitude. The primary purpose of
      this article is to provide an overview of contemporary cochlear implants from the
      perspective of two designers of implant systems. That perspective includes the
      anatomical situation presented by the deaf cochlea and how the different parts of
      an implant system (including the user's brain) must work together to produce the
      best results. In particular, we present the design considerations just mentioned
      and then describe in detail how the current levels of performance have been
      achieved. We also describe two recent advances in implant design and performance.
      In concluding sections, we first present strengths and limitations of present
      systems and then offer some possibilities for further improvements in this
      technology. In all, remarkable progress has been made in the development of
      cochlear implants but much room still remains for improvements, especially for
      patients presently at the low end of the performance spectrum.

PMID- 18816423
TI  - Considerations for design of future cochlear implant electrode arrays: electrode
      array stiffness, size, and depth of insertion.
AB  - The level of hearing rehabilitation enjoyed by cochlear implant (CI) recipients
      has increased dramatically since the introduction of these devices. This
      improvement is the result of continual development of these systems and the
      inclusion of subjects with less severe auditory pathology. Developments include
      advanced signal processing, higher stimulation rates, greater numbers of
      channels, and more efficient electrode arrays that are less likely to produce
      insertion damage. New directions in the application of CIs, particularly in
      combined acoustic and electrical stimulation, and increasing performance
      expectations will place greater demands on future electrode arrays. Specifically,
      the next generation of arrays must be reliably inserted without damage, must
      maintain residual acoustic function, and may need to be inserted more deeply. In
      this study, we measured the mechanical properties of eight clinical and prototype
      human CI electrode arrays and evaluated insertion trauma and insertion depth in
      79 implanted cadaver temporal bones. We found that the size and shape of the
      array directly affect the incidence of observed trauma. Further, arrays with
      greater stiffness in the plane perpendicular to the plane of the cochlear spiral
      are less likely to cause severe trauma than arrays with similar vertical and
      horizontal stiffness.

PMID- 18816424
TI  - Restoring hearing symmetry with two cochlear implants or one cochlear implant and
      a contralateral hearing aid.
AB  - With today's technology and the demonstrated success of cochlear implantation,
      along with expanded candidacy criteria, the opportunity to provide optimal
      hearing to both ears for individuals with severe-to-profound hearing loss is
      greater than ever. This article reviews the advantages of binaural hearing and
      the disadvantages of hearing with only one ear or hearing with two ears with
      significantly different sound thresholds. A case study is presented that
      demonstrates the benefit of bimodal hearing (i.e., a cochlear implant [CI] in one
      ear and a contralateral hearing aid [HA]) in a nontraditional CI candidate with
      asymmetrical hearing thresholds. Then, selected studies in adult recipients who
      use a CI and contralateral HA or who use two CIs are summarized. The data overall
      demonstrate that bilateral CI recipients, traditional bimodal recipients, and
      nontraditional bimodal recipients experience substantial binaural hearing
      advantages, including improved speech recognition in noise, localization, and
      functional everyday communication. These results indicate that bilateral
      stimulation of the auditory system through a CI and contralateral HA or two CIs
      is beneficial and should become standard clinical practice.

PMID- 18816425
TI  - Integration of acoustic and electrical hearing.
AB  - For some individuals with severe high-frequency hearing loss, hearing aids cannot
      provide a satisfactory improvement in speech recognition. However, these same
      patients often have too much residual hearing to qualify as candidates for a
      cochlear implant. Here we describe results with the Iowa/Nucleus Hybrid cochlear
      implant, which is designed to preserve the patient's residual low-frequency
      hearing while at the same time supplementing their high-frequency hearing through
      electrical stimulation. The advantages of this approach are presented, including
      improved speech recognition in competing backgrounds as compared with traditional
      cochlear implants. The results with the Iowa/Nucleus Hybrid device demonstrate
      the ability of the auditory system to integrate acoustic and electrical
      stimulation, even under conditions of severe distortions to the normal cochlear
      place-frequency mapping.

PMID- 18816426
TI  - Music perception in cochlear implant users and its relationship with
      psychophysical capabilities.
AB  - This article describes issues concerning music perception with cochlear implants,
      discusses why music perception is usually poor in cochlear implant users, reviews
      relevant data, and describes approaches for improving music perception with
      cochlear implants. Pitch discrimination ability ranges from the ability to hear a
      one-semitone difference to a two-octave difference. The ability to hear rhythm
      and tone duration is near normal in implantees. Timbre perception is usually
      poor, but about two-thirds of listeners can identify instruments in a closed set
      better than chance. Cochlear implant recipients typically have poor melody
      perception but are aided with rhythm and lyrics. Without rhythm or lyrics, only
      about one-third of implantees can identify common melodies in a closed set better
      than chance. Correlations have been found between music perception ability and
      speech understanding in noisy environments. Thus, improving music perception
      might also provide broader clinical benefit. A number of approaches have been
      proposed to improve music perception with implant users, including encoding
      fundamental frequency with modulation, "current-steering," MP3-like processing,
      and nerve "conditioning." If successful, these approaches could improve the
      quality of life for implantees by improving communication and musical and
      environmental awareness.

PMID- 18816427
TI  - NAD(P)H oxidase and endothelial dysfunction.
AB  - The regulation of endothelial function plays an important role in the development
      and progression of metabolic and cardiovascular diseases. A critical determinant
      of endothelial function is the balance between nitric oxide and reactive oxygen
      species. Endothelium-derived NO availability can be limited by enhanced formation
      of reactive oxygen species. Major sources of reactive oxygen species in the
      vessel wall are NAD(P)H oxidase complexes. This review summarizes the impact of
      vascular NAD(P)H oxidase-derived reactive oxygen species on atherosclerosis and
      endothelial dysfunction. Changes in NAD(P)H oxidase expression and activity have
      clinical implications. Mutations in NAD(P)H oxidase subunits can lead to impaired
      oxidative burst in leukocytes and chronic granulomatous disease. In contrast,
      normalization of increased expression and activity of NAD(P)H oxidase in
      endothelial dysfunction and vascular disorders can be considered as a novel
      therapeutic strategy in the treatment of cardiovascular diseases.

PMID- 18816428
TI  - Quantitative transcript profiling reveals down-regulation of A sterol pathway
      relevant gene and overexpression of artemisinin biogenetic genes in transgenic
      Artemisia annua plants.
AB  - To investigate the dynamic fluctuation of terpenoid relevant transcriptomics in
      transgenic ARTEMISIA ANNUA plants that express the genomic integrated antisense
      squalene synthase gene ( ASSS), we have quantified the transcript levels of the
      sterol anabolic SS gene as well as artemisinin biogenetic amorphadiene synthase
      (ADS), cytochrome P450 monooxygenase (CYP71AV1) and cytochrome P450 reductase
      (CPR) genes by real-time fluorescent quantitative polymerase chain reaction (RFQ
      PCR). The SS mRNA level in transgenic plants sharply droped to 7.4 % - 55.3 % (i.
      e., 44.7 - 92.6 % reduction as the wild-type control), strongly implying that the
      expression of endogenous SS gene is significantly suppressed by the exogenous
      ASSS gene. In a synchronous fashion, ADS, CYP71AV1 and CPR mRNA levels elevated
      with the decline of SS mRNA level in transgenic plants, and the maximal ADS,
      CYP71AV1 and CPR mRNA levels in transgenic plants were 3.0-, 4.4- and 2.5-fold,
      respectively, higher than those in the control. Without a lethal effect but with
      a distinguishable impact on the organogenesis and morphology of transgenic
      plants, the down-regulation of SS gene has also led to the coordinated
      overexpression of ADS, CYP71AV1 and CPR genes together with the overproduction of
      artemisinin although no fully perfect correlation among the available
      experimental data has been shown.

PMID- 18816429
TI  - Flavonoids from Iris songarica and their antioxidant and estrogenic activity.
AB  - A new dihydroflavonol, songaricol ( 1) and seven known flavonoids, ayamenin A (
      2), irisflavone A ( 3), 5,7-dihydroxy-2',6-dimethoxyisoflavone ( 4), irilin B (
      5), 5,3'-dihydroxy-7,8,2'-trimethoxyisoflavone ( 6) and irisoid A ( 7) were
      isolated from rhizome and roots of IRIS SONGARICA. Structure elucidation of 1 was
      achieved through extensive NMR and circular dichroism techniques. Compounds 1, 5
      and 7 showed antioxidant activity in HL-60 cells (IC50 values of 21, 11 and 3.8
      microg/mL), whereas 2, 5 and the previously isolated irisone B were able to show
      estrogenic response (EC50 values of 305.5, 159.7 and 322.0 microg/mL) in yeast
      cells expressing human estrogen receptor (ER-alpha).

PMID- 18816430
TI  - Structure-activity relationship of pentacylic triterpene esters from Uncaria
      rhynchophylla as inhibitors of phospholipase Cgamma1.
AB  - A systematic structure-activity relationship of 3beta-hydroxy-27- P- E
      coumaroyloxyurs-12-en-28-oic acid ( 7), a triterpene ester isolated from UNCARIA
      RHYNCHOPHYLLA as a phospholipase Cgamma1 inhibitor, was undertaken with a view
      toward elucidating its chemical mode of action on PLCgamma1. Related derivatives
      and analogues of 7 were synthesized and their inhibitory activities against
      PLCgamma1 were evaluated IN VITRO. The results indicate that 3-OH and 27
      esterification may be essential, and that 28-COOH and the 2' double bond appear
      to be important for activity. Furthermore, the compound possessing a P
      coumaroyloxy at position 27 rather than at the 3 and 28 positions shows the
      greatest inhibitory activity against PLCgamma1. Therefore, this inhibitor will be
      providing a chemical lead for the further development of cancer chemopreventive
      or cancer chemotherapeutic agents that have lower toxicity against normal
      tissues.

PMID- 18816431
TI  - Effect of safranal on extracellular hippocampal levels of glutamate and aspartate
      during kainic Acid treatment in anesthetized rats.
AB  - In this study, the effect of safranal, a constituent of CROCUS SATIVUS L.,
      pretreatment on concomitant changes in the extracellular hippocampal levels of
      EAA (glutamate and aspartate) following systemic administration of KA was
      investigated in anesthetized rats. Safranal (72.75 mg/kg or 291 mg/kg, I. P.) was
      injected 40 min before KA (15 mg/kg, I. P.). A group of rats also received DZP
      (15 mg/kg, I. P.) 20 min prior to KA administration. The basal hippocampal
      concentrations of glutamate and aspartate were estimated to be 0.51 +/- 0.02
      microM and 0.28 +/- 0.01 microM, respectively. Basal EAA levels were not affected
      by pretreatment with safranal. Following KA injection, there was a significant
      increase (p < 0.001) in the extracellular glutamate and aspartate levels (about 5
      fold and 3-fold, respectively) at 80 min after injection. However, the kainite
      evoked release of EAA was significantly reduced by DZP (p < 0.001) and safranal
      (291 mg/kg, I. P.; p < 0.001). The results of this study show that acute systemic
      injection of safranal reduces the extracellular concentrations of glutamate and
      aspartate in the rat hippocampus following KA administration.

PMID- 18816432
TI  - [A "simple" method for correction of the Apert's hand].
AB  - In view of the multiple malformations in patients with Apert syndrome, numerous
      operations need to be carried out on the skull, midface, jaws, hands and in some
      cases also feet. We describe here a simplified surgical approach to hand surgery
      that enables several operative steps to be performed during one session and thus
      reduces the total number of surgical interventions. After visualising with MSCT
      angiography the bone and soft-tissue malformations and blood vessels, the
      operation is planned carefully. Transection and removal of the bony and
      cartilaginous bridges between the symphalangeal fingers is followed by placement
      of silastic sheets between the separated fingers for a period of 2 - 3 weeks to
      help form well-vascularised tissue over the spongy bone, which is then covered by
      full-thickness skin graft to promote healing. Depending on the severity of the
      Apert hand, numerous surgical procedures can be performed together at one and the
      same session. This is a simplified method in which the thumb is also straightened
      either during the same intervention or at a later date. This approach is
      explained with the help of three of our cases.

PMID- 18816435
TI  - New amides of 5-(4-chlorobenzoyl)aminoorotic acid: their synthesis and biological
      activity.
AB  - The synthesis and in-vitro biological evaluation of the amide series 4 of 5-(4
      chlorobenzoyl)aminoorotic acid 2 are presented. The biological properties of a
      few 5-(4-chlorobenzoyl)amino-2,6-dihydroxy-N-substituted-4-pyrimidinecarboxamide
      derivatives 4 tested here were compared with those of the isosteric isothiazole
      derivative MR-2/94 (5-(4-chlorobenzoyl)amino-N-(4-chlorophenyl)-3-methyl-4
      isothiazolecarboxamide), which possesses a strong immunosuppressive and anti
      inflammatory activity [1, 2], It must be suggested that replacement of the
      isothiazole by a pyrimidine core ring system resulted in considerable lowering of
      the anti-inflammatory and immunotropic actions of the obtained amides.
      Physicochemical properties of 2-(4-chlorophenyl)-6,8-dihydroxy-4H-pyrimido[5,4-d]
      1,3-oxazin-4-on 3 are also briefly described.

PMID- 18816436
TI  - Recombinant glycans on an S-layer self-assembly protein: a new dimension for
      nanopatterned biomaterials.
AB  - Crucial biological phenomena are mediated through carbohydrates that are
      displayed in a defined manner and interact with molecular scale precision. We lay
      the groundwork for the integration of recombinant carbohydrates into a
      "biomolecular construction kit" for the design of new biomaterials, by utilizing
      the self-assembly system of the crystalline cell surface (S)-layer protein SgsE
      of Geobacillus stearothermophilus NRS 2004/3a. SgsE is a naturally O-glycosylated
      protein, with intrinsic properties that allow it to function as a nanopatterned
      matrix for the periodic display of glycans. By using a combined
      carbohydrate/protein engineering approach, two types of S-layer neoglycoproteins
      are produced in Escherichia coli. Based on the identification of a suitable
      periplasmic targeting system for the SgsE self-assembly protein as a cellular
      prerequisite for protein glycosylation, and on engineering of one of the natural
      protein O-glycosylation sites into a target for N-glycosylation, the
      heptasaccharide from the AcrA protein of Campylobacter jejuni and the O7
      polysaccharide of E. coli are co- or post-translationally transferred to the S
      layer protein by the action of the oligosaccharyltransferase PglB. The degree of
      glycosylation of the S-layer neoglycoproteins after purification from the
      periplasmic fraction reaches completeness. Electron microscopy reveals that
      recombinant glycosylation is fully compatible with the S-layer protein self
      assembly system. Tailor-made ("functional") nanopatterned, self-assembling
      neoglycoproteins may open up new strategies for influencing and controlling
      complex biological systems with potential applications in the areas of
      biomimetics, drug targeting, vaccine design, or diagnostics.

PMID- 18816437
TI  - Interpretation of positive transcription-mediated amplification test results from
      polymerase chain reaction-negative samples obtained after treatment of chronic
      hepatitis C.
AB  - The Siemens VERSANT transcription-mediated amplification (TMA) assay is extremely
      sensitive for the detection of hepatitis C virus (HCV) RNA in serum. Eleven of
      180 subjects in the Hepatitis C Antiviral Long-term Treatment against Cirrhosis
      (HALT-C) Trial who achieved polymerase chain reaction (PCR)-defined sustained
      virological response (SVR) at week 72 also had TMA-positive results from the same
      blood draw; six were positive on repeat testing. We report the follow-up on these
      11 patients, and the reproducibility of TMA test results from PCR-negative
      samples in relationship to antiviral treatment outcome. Peginterferon and
      ribavirin treatment was initiated in 1145 prior interferon nonresponders with
      advanced hepatic fibrosis. Treatment was continued for 48 weeks if patients had
      undetectable HCV RNA by PCR at treatment week 20. Frozen serum samples from weeks
      12, 20, 24, 48, and 72 were subsequently tested by TMA. Nine of the 11 patients
      returned for testing (median, 30 months after the week 72 visit), and all had
      undetectable HCV RNA by TMA and PCR. Among 759 PCR-negative samples obtained
      during treatment that were tested twice by TMA, 17% overall exhibited
      consistently positive results, and 21% exhibited inconsistently positive results.
      SVR was more likely if TMA was consistently negative than if consistently or
      inconsistently positive. With continued treatment, patients with inconsistently
      positive TMA results were more likely to become TMA-negative than TMA-positive (P
      < 0.0001). CONCLUSION: In PCR-negative samples, positive TMA results may indicate
      the presence of low levels of HCV RNA. However, because patients with positive
      TMA results may achieve SVR, management decisions during therapy should not be
      based on a single positive TMA test result.

PMID- 18816438
TI  - Expression profile and estrogenic regulation of anti-Mullerian hormone during
      gonadal development in pejerrey Odontesthes bonariensis, a teleost fish with
      strong temperature-dependent sex determination.
AB  - Pejerrey is a teleost fish presenting a strong temperature-dependent sex
      determination. This study was conducted to clone pejerrey amh cDNA, analyze its
      expression profile during thermal and endocrine manipulation of gonadal
      differentiation, and compare its expression with that of gonadal aromatase
      (cyp19a1). Amh displayed higher expression at masculinizing than at feminizing
      temperatures during the gonadal differentiation period. Its expression at an
      intermediate temperature (females 1:1 males), was high in half of the larvae and
      low in the other half. Cyp19a1 showed a reciprocal expression pattern to that of
      amh both individually- and temperature-wise. Increased cyp19a1 and amh expression
      was observed before morphological gonadal differentiation. Amh expression in
      larvae feminized by administration of estradiol or masculinized by the
      administration of an aromatase inhibitor was down- and up-regulated,
      respectively. These results show that amh plays a critical role in testicular
      differentiation and it is apparently modulated by estrogens in this species.

PMID- 18816439
TI  - Nuclear receptor BgFTZ-F1 regulates molting and the timing of ecdysteroid
      production during nymphal development in the hemimetabolous insect Blattella
      germanica.
AB  - Postembryonic development of holometabolous and hemimetabolous insects occurs
      through successive molts triggered by 20-hydroxyecdysone (20E). The molecular
      action of 20E has been extensively studied in holometabolous insects, but data on
      hemimetabolous are scarce. We have demonstrated that during the nymphal
      development of the hemimetabolous insect Blattella germanica, 20E binds to the
      heterodimeric receptor formed by the nuclear receptors BgEcR-A and BgRXR
      activating a cascade of gene expression, including the nuclear receptors BgE75
      and BgHR3. Herein, we report the characterization of BgFTZ-F1, another nuclear
      hormone receptor involved in 20E action. BgFTZ-F1 is activated at the end of each
      instar, and RNAi has demonstrated that BgHR3 is needed for BgFTZ-F1 activation,
      and that BgFTZ-F1 has critical functions of during the last nymphal instar.
      Nymphs with silenced BgFTZ-F1 cannot ecdyse, arrest development, and show
      structures of ectodermal origin duplicated. BgFTZ-F1 also controls the timing of
      the ecdysteroid molting pulse.

PMID- 18816440
TI  - Expression of the fras1/frem gene family during zebrafish development and fin
      morphogenesis.
AB  - Mouse studies have highlighted the requirement of the extracellular matrix Fras
      and Frem proteins for embryonic epidermal adhesion. Mutations of the genes
      encoding some of these proteins underlie the blebs mouse mutants, whereas
      mutations in human FRAS1 and FREM2 cause Fraser syndrome, a congenital disorder
      characterized by embryonic blistering and renal defects. We have cloned the
      zebrafish homologues of these genes and characterized their evolutionary
      diversification and expression during development. The fish gene complement
      includes fras1, frem1a, frem1b, frem2a, frem2b, and frem3, which display complex
      overlapping and complementary expression patterns in developing tissues including
      the pharyngeal arches, hypochord, musculature, and otic vesicle. Expression
      during fin development delineates distinct populations of epidermal cells which
      have previously only been described at a morphological level. We detect
      relatively little gene expression in epidermis or pronephros, suggesting that the
      essential role of these proteins in mediating their development in humans and
      mice is recently evolved.

PMID- 18816441
TI  - Differential survival response of neurons to exogenous GDNF depends on the
      presence of skeletal muscle.
AB  - Glial cell line-derived neurotrophic factor (GDNF) is known as a potent survival
      factor for neurons in vitro and in vivo. The current study investigated the
      effects of a single in utero injection with GDNF in both wild-type and Myf5-/
      :MyoD-/- embryos. The embryos in the latter group, denoted double mutants (DM),
      do not contain skeletal muscle and associated neurotrophic factors due to lack of
      myogenesis and, therefore, neurons of the central and peripheral nervous system
      undergo excessively occurring programmed cell death (EPCD). We found that
      treatment with GDNF had no effect on wild type neuronal numbers in any of the
      anatomic locations investigated. However, GDNF rescued the neurons of the facial
      motor nucleus, the mesencephalic nucleus and the median motor column in the
      absence of skeletal muscle. The findings of the current study agree with previous
      reports that compromised mouse neurons have increased survival response to GDNF.

PMID- 18816442
TI  - Multiple evolutionarily conserved enhancers control expression of Eya1.
AB  - Eya1 is a homolog of eyes absent in Drosophila, and essential for various organ
      formations in vertebrates. Mouse and chick Eya1 shows dynamic expression pattern
      in early development. We identified ten independent Eya1 enhancers by screening
      evolutionarily conserved sequences. They exhibited enhancer activities in
      Hensen's node, neural tube, migrating neural crest cells, otic vesicle, olfactory
      placode, cranial ganglia, and somites at HH6-17 of chick embryo. The sum of the
      enhancer activities of the enhancers covers the endogenous expression domains of
      Eya1 common to chick and mouse. Enhancer activities were also observed in species
      specific expression domains such as trigeminal ganglia and brain. Mutational
      study of one of the enhancers revealed that the enhancer is composed of positive
      and negative cis-regulatory elements. Thus, we successfully identified a
      comprehensive group of enhancers around Eya1 locus, which are probably involved
      in the control of the complex expression pattern of Eya1 in vivo.

PMID- 18816443
TI  - Endoscopic anatomy of sphenoid sinus for pituitary surgery.
AB  - Endoscopic endonasal transsphenoidal approach to the sellar region yields an
      alternative to classical microsurgical approaches. Endoscopes provide images that
      differ from microscopic view. This study aimed to highlight surgical landmarks
      and their anatomical relationships for pituitary surgery through endoscopic
      perspective. Ten sides of five adult cadaveric heads with red-colored latex
      injected arteries were evaluated. Endoscopic dissections were performed and
      measurements were done in the sphenoid sinuses before and after the removal of
      bony structures in all the aspects. Endoscopic vision of the sellar region
      enabled a wide panoramic perspective and detailed inspection. The measurements,
      in general, indicated the variations in the bony structures and soft tissues. The
      width of the pituitary, which is the distance between the medial margins of the
      carotid prominences, was measured as 21 +/- 2.5 mm and the distance between the
      medial margin of the carotid prominences at the lower margin of the pituitary was
      18 +/- 3.1 mm. After the bony structures were removed, further measurements were
      done. The width of the pituitary, which is the distance between the medial
      margins of the anterior curvature of the ICA, was measured as 23.2 +/- 3 mm,
      while the distance between the posterior curvature of the ICA was 19.7 +/- 4.9
      mm. Endoscopic view provided superior detailed visualization of the close
      relationships between pituitary gland, internal carotid arteries, and optic
      nerves. This facilitated exact evaluation for variations, which could result in
      more effective and safe surgery. However, these variations again emphasize the
      necessity of preoperative radiological evaluation in each case.

PMID- 18816444
TI  - Absence of the long head of the biceps tendon associated with glenoid dysplasia
      and posterior labral tear.
AB  - Anatomic variations in the insertion of the long head of the biceps tendon and
      superior labral complex have been described (Erickson et al. [1992] AJR Am. J.
      Roentgenol. 158:1091-1096; Kreitner et al. [1998] AJR Am. J. Roentgenol. 170:599
      605; Mariani et al. [1997] Arthroscopy 13:499-501; Vangsness Jr. et al. [1994] J.
      Bone Joint Surg. Br. 76:951-954). To the authors' knowledge, there have been only
      five reported cases of congenital absence of the long head of the biceps tendon.
      Three of these cases were associated with anterior shoulder instability, one with
      a superior labral anterior posterior lesion and one simply with shoulder pain.
      This is the first reported case of congenital absence of the biceps tendon
      associated with glenoid dysplasia and a posterior labral tear.

PMID- 18816445
TI  - Re: Dr. Holzheimer's affirmation of the findings of McVay and Anson (1940) and
      Condon(1964).

PMID- 18816447
TI  - Diverse roles of E-cadherin in the morphogenesis of the submandibular gland:
      insights into the formation of acinar and ductal structures.
AB  - The formation of acinar and ductal structures during epithelial tissue branching
      morphogenesis is not well understood. We report that in the mouse submandibular
      gland (SMG), acinar and ductal cell fates are determined early in embryonic
      morphogenesis with E-cadherin playing pivotal roles in development. We identified
      two morphologically distinct cell populations at the single bud stage, destined
      for different functions. The outer layer of columnar cells with organized E
      cadherin junctions expressed the neonatal acinar marker B1 by E13.5,
      demonstrating their acinar fate. The interior cells initially lacked distinct E
      cadherin junctions, but with morphogenesis formed cytokeratin 7 (K7) -positive
      ductal structures with organized E-cadherin junctions and F-actin filaments.
      Inhibition of E-cadherin function with either siRNA or function blocking antibody
      caused extensive apoptosis of ductal cells and aberrantly dilated lumens,
      providing the first evidence that E-cadherin regulates ductal lumen formation
      during branching morphogenesis of the salivary gland.

PMID- 18816448
TI  - Activation of the Wnt/beta-catenin signaling reporter in developing mouse
      olfactory nerve layer marks a specialized subgroup of olfactory ensheathing
      cells.
AB  - Wnt reporter TOPgal mice carry a beta-galactosidase (betagal) gene under the
      control of the Wnt/beta-catenin signaling responsive elements. We found that the
      intensely immunolabeled betagal+ cells were co-immunolabeled with Nestin and
      formed a tangentially oriented single-cell layer in the "connecting or docking
      zone" where the olfactory sensory axons attached to the brain surface during mid
      gestation. During early postnatal development, betagal+ cells were located in the
      inner olfactory nerve layer (ONLi) and co-labeled with olfactory ensheathing cell
      (OEC) markers S100beta and NPY but not with lineage-specific markers for neurons,
      oligodendrocytes, astrocytes, and microglia, demonstrating that the TOPgal marked
      a subpopulation of OECs. By confocal microscopy, we found that TOPgal activated
      processes extended along the developing glomerulus and formed multiple tunnel
      like structures that ensheathe and bridge olfactory sensory axonal bundles from
      ONLi to the glomerulus, which may play a key role in glomerulus formation and
      convergent sorting of the peripheral olfactory axons.

PMID- 18816449
TI  - Experience in identifying the venous drainage of the adrenal gland during
      laparoscopic adrenalectomy.
AB  - Laparoscopic adrenalectomy (LA) is the procedure of choice for most adrenal
      tumors. An important part of LA is the early identification and ligation of the
      adrenal veins. The venous drainage from each adrenal gland is usually via a
      single vein: the right vein draining into the inferior vena cava (IVC) and the
      left vein into the left renal vein. Although infrequent, variable venous drainage
      has been documented. The aim of the study was to clarify if LA identified venous
      drainage and its variants. Between January 1999 and January 2008, 142 consecutive
      patients underwent LA. Adrenal vein anatomy was documented on a prospective
      database. In total, 142 patients underwent 162 LA (right = 62, left = 66,
      bilateral = 17). All adrenal veins were identified at the time of laparoscopy.
      For 157 LA, the adrenal venous drainage was constant: right vein drained into the
      IVC and left vein drained into left renal vein. Five patients had adrenal vein
      variants: two right veins draining separately into IVC (n = 1), two right veins
      draining into the IVC and right renal vein (n = 1), and two left veins draining
      separately into the left renal vein (n = 3). Adrenal vein variants were present
      in patients with phaeochromocytomas (n = 4) or adrenocortical carcinoma (n = 1).
      The laparoscopic approach allowed an excellent view of the main adrenal venous
      anatomy. This has helped confirm the constant nature of the venous drainage and
      successfully identify variant adrenal veins.

PMID- 18816450
TI  - Anatomical variations of the iliolumbar vein with application to the anterior
      retroperitoneal approach to the lumbar spine: a cadaver study.
AB  - Objectives of this study include identification of lumbosacral venous variations,
      designation of a critical area of dissection for surgical exposure, and
      comparison between both male/female and right/left-sided anatomy. Attempts were
      made to provide anatomic nomenclature that accurately describes these structures.
      Thirty-eight iliolumbar venous systems in 20 cadavers (11 females/9 males) were
      dissected. Each system was identified as one of three patterns of variation:
      common venous trunk (combining ascending lumbar and iliolumbar venous systems)
      with distal veins, common venous trunk without distal veins, and venous systems
      without a common venous trunk. Dimensions including distances to the inferior
      vena cava (IVC) confluence, the obturator nerve, and the lumbosacral trunk, and
      venous stem length were obtained to aid surgical dissection. Differences between
      males and females and those between right and left sides were compared. Anterior
      lumbosacral venous variations could be organized into three groups. A Type 1
      venous system (common venous trunk with distal veins) was most common (53% of
      systems). The anatomical name "lateral lumbosacral veins" adequately describes
      the anatomical location of these veins and does not assume a direction of venous
      flow or the lack of individual distal veins. A critical area bordered by the
      obturator nerve anteriorly, the psoas muscle laterally, the spinal column
      medially, and sacrum posteriorly within 8.2 cm of the IVC confluence should be
      defined to adequately dissect the lateral lumbosacral veins. Differences in male
      and female lateral lumbosacral venous anatomy do not alter surgeon's approach to
      the anterior lumbar spine.

PMID- 18816451
TI  - Anatomical development of urinary bladder during the fetal period.
AB  - The aim of this study was to determine the development, location, and size of the
      urinary bladder during the fetal period. The study was performed on 149 human
      fetuses between 9 and 40 weeks of gestation. The location of the urinary bladder
      with respect to transverse plane between the highest point of pubic symphysis and
      the sacral promontory and median sagittal plane was first determined. The
      dimensions and the angle of the urinary bladder were measured, and bladder shapes
      were determined. In addition, the edges of the vesical trigone were measured.
      There was no significant difference between sexes for any of the parameters (P >
      0.05). A significant correlation was observed between all parameters and
      gestational age (P < 0.001). The urinary bladder was located above the transverse
      plane in most of the cases (83%) and in the median sagittal plane in every case.
      It was determined that the angle of bladder did not change and the mean value of
      the angle was 151 degrees during the fetal period. Bladder was categorized into
      four different shapes (ellipsoid, round, cuboid, and triangular), and the most
      common shape found during the fetal period was cuboid. The vesical trigone was an
      isosceles triangle during the fetal period. The new data provided by this study
      will enable evaluation of the development of the fetal urinary bladder, and
      should be useful in several fields such as anatomy, fetopathology, medical
      imaging, obstetrics, and pediatric urology.

PMID- 18816452
TI  - Transport proteins (carriers) of mitochondria.
AB  - Mitochondria are subcellular structures essential to the aerobic eukaryotic cell.
      Their role extends much beyond their basic reactions of oxidative
      phosphorylation. It encompasses the steps critical for cellular metabolic
      pathways, for apoptosis, and for other processes such as antiviral signaling.
      This short review is limited to transport proteins (carriers) that catalyze the
      transport of metabolites across the inner mitochondrial membrane and thus link
      metabolic pathway reactions in the cytosol and the mitochondrial matrix. Such
      transport must minimally affect the electrochemical proton gradient essential for
      oxidative phosphorylation (chemiosmotic mechanism of oxidative phosphorylation).
      Many of these transport proteins belong to a family of membrane proteins, and the
      major part of this review will consider their structures and functions. First
      studies of these transporters were carried out with intact mitochondria and with
      inhibitors that appeared transporter-specific. Such an inhibitor was then
      utilized in the first purification of one of these transporter proteins. Its
      substrate-specificity was then established after functionally active
      incorporation into liposomes. Questions about copurification of other
      transporters and thus a definitive identification of transported substrate with
      the purified protein were resolved definitively only after heterologous
      expression in bacteria, most generally as inclusion bodies, and followed by
      reconstitution in liposomes. Site-specific mutations permitted the identification
      of amino acids essential to their transport function. These mutagenesis studies
      then also helped interpret human diseases with mutations in these transport
      proteins. The high-resolution structure of a member of this transporter protein
      family dramatically advanced these studies. It raised new questions because this
      structure complexed with a high-affinity inhibitor showed a monomeric protein,
      while purification and inhibitor stoichiometry studies suggest a functional
      homodimeric transport protein. Remaining key questions need to address: the
      homodimeric nature of the transporters, details of their transport mechanism, and
      the functional identification of many members of this family whose existence has
      only been suggested from genomic data.

PMID- 18816453
TI  - Enantioselective analysis of primaquine and its impurity quinocide by capillary
      electrophoresis.
AB  - A capillary electrophoretic (CE) method for the baseline separation of the
      enantiomers of primaquine diphosphate (PQ) and quinocide (QC) (a major
      contaminant) in pharmaceutical formulations is proposed. Both components were
      separated under the following conditions: 50 mm tris phosphate buffer (pH 3.0)
      containing 15 mm hydroxypropyl-gamma-cyclodextrin (HP-gamma-CD) as background
      electrolyte; applied voltage, 16 kV; capillary temperature, 25 degrees C;
      detection wavelength, 254 nm; hydrostatic injection, 10 s. The separations were
      conducted using a 35 cm length and 50 microm i.d. uncoated fused silica capillary
      column. Under the optimized conditions, the components were successfully
      separated in about 5 min. Intraday precision of migration time and corrected peak
      areas when expressed as relative standard deviation ranged from 0.17 to 0.45 and
      2.60 to 3.94%, respectively, while the interday precision ranged from 2.59 to
      4.20 and 3.15 to 4.21%, respectively. After the validation exercise, the proposed
      method was applied for the determination of QC impurity in PQ formulations.

PMID- 18816454
TI  - Simultaneous determination of triptolide, tripdiolide and tripterine in human
      urine by high-performance liquid chromatography coupled with ion trap atmospheric
      pressure chemical ionization mass spectrometry.
AB  - An accurate and selective method for the simultaneous determination of
      triptolide, tripdiolide and tripterine in human urine using hydrocortisone as an
      internal standard (IS) by high-performance liquid chromatography coupled with
      atmospheric-pressure chemical ionization mass spectrometry in negative ion mode
      has been developed. After triptolide, tripdiolide and tripterine in human urine
      were extracted with ethyl acetate and cleaned by solid-phase extraction with
      C(18) cartridges, a satisfactory separation was achieved on an XDB C(18) short
      column (30 x 2.1 mm i.d., 3 microm) using the mobile phase of acetic acid
      ammonium acetate (5 mmol/L, pH = 4.5)-acetonitrile-methanol in gradient elution.
      Detection was operated by APCI in selected ion monitoring mode. The target ions
      m/z 359, m/z 375, m/z 449 and m/z 419 were selected for the quantification of
      triptolide, tripdiolide, tripterine and IS, respectively. The linear range was
      1.0-100.0 ng mL(-1), and the limits of quantification in human urine were found
      to be 0.1-0.5 ng mL(-1) for the three compounds. The precisions (CV%) and
      accuracies were 6.6-12.9 and 85.1-97.0%, respectively. The developed method could
      be applied to the determination of triptolide, tripdiolide and tripterine in
      human urine for diagnosis of the intoxication and for forensic purposes.

PMID- 18816455
TI  - Measurement of xenobiotics in saliva: is saliva an attractive alternative matrix?
      Case studies and analytical perspectives.
AB  - The use of saliva for measuring xenobiotic concentrations has been practiced for
      a number of years. While the use of saliva has been generally reserved for the
      analysis of diagnostic and forensic/toxicology samples, attempts have been made
      to further enhance the value of saliva as an alternate matrix to those of plasma
      and serum. It is understood that saliva represents a handy tool for therapeutic
      drug monitoring (TDM) as it offers certain distinctive advantages. This scope of
      this review encompasses the following: (a) a comprehensive view of saliva as an
      alternate matrix for either plasma or serum to understand the
      pharmacokinetic/pharmacodynamic (PK/PD) characteristics; (b) an account of the
      factors contributing to the observed variability in salivary monitoring; (c) a
      tabular compilation of diverse case studies of xenobitoics belonging to different
      therapeutic classes with emphasis on assay methodology and applicable
      analytical/biopharmaceutical/pharmacokinetic findings; (d) relevant thoughts on
      assay procedures as they relate to salivary monitoring; and (e) some
      representative case studies highlighting the new thinking on the use of saliva
      outside of traditional TDM. Overall, based on the review, saliva represents a
      valuable TDM tool for a number of xenobiotics. While parent compound and phase I
      metabolite(s) for many xenobiotics have been generally quantifiable in saliva,
      phase II metabolites have not generally been detected in saliva. Therefore saliva
      samples could also be used to answer some specific PK/PD questions during the
      drug development process, if applicable. However, the development and validation
      of the assay in saliva needs to be carried out carefully with particular focus on
      proper sample collection, processing and storage to ensure the stability of the
      xenobiotics and with the same rigor as applied to plasma, serum and urine
      matrices.

PMID- 18816456
TI  - Preparative isolation and purification of alkannin/shikonin derivatives from
      natural products by high-speed counter-current chromatography.
AB  - Alkannin and shikonin (A/S) and their derivatives have been found in the roots of
      several Boraginaceous species and are also produced through plant tissue
      cultures. The chiral compounds A/S are potent pharmaceutical substances with a
      wide spectrum of biological and pharmacological activities like wound healing,
      antimicrobial, anti-inflammatory, anticancer and antioxidant activity. High-speed
      counter-current chromatography (HSCCC) was applied for the first time to the
      separation, preparative isolation and purification of A/S and their esters from
      extracts of Alkanna tinctoria roots, as well as commercial samples. The
      constituents of HSCCC fractions and their purity were determined by high
      performance liquid chromatography-diode array detection-mass spectrometry (HPLC
      DAD-MS), since DAD cannot detect oligomeric A/S derivatives that are present in
      most of the samples containing the respective monomeric derivatives. The purity
      of HSCCC fractions was compared with the one of fractions isolated by column
      chromatography (CC) using as stationary phases silica gel and Sephadex LH-20. As
      shown, the purity of monomeric alkannin/shikonin was greater by HSCCC than CC
      separation of commercial A/S samples.

PMID- 18816457
TI  - Molecular dynamics with restrictions derived from optical spectra.
AB  - The information about molecular structure coded in the optical spectra must often
      be deciphered by complicated computational procedures. A combination of spectral
      modeling with the molecular dynamic simulations makes the process simpler, by
      implicit accounting for the inhomogeneous band broadening and Boltzmann averaging
      of many conformations. Ideally, geometries of studied systems can be deduced by a
      direct confrontation of such modeling with the experiment. In this work, the
      comparison is enhanced by restrictions to molecular dynamics propagations based
      on the Raman and Raman optical activity spectra. The methodology is introduced
      and tested on model systems comprising idealized H(2)O(2), H(2)O(3) molecules,
      and the alanine zwitterion. An additional gradient term based on the spectral
      overlap smoothed by Fourier transformation is constructed and added to the
      molecular energy during the molecular dynamics run. For systems with one
      prevalent conformation the method did allow to enrich the Boltzmann ensemble by a
      spectroscopically favored structure. For systems with multiconformational
      equilibria families preferential conformations can be selected. An alternative
      algorithm based on the comparison of the averaged spectra with the reference
      enabling iterative updates of the conformer probabilities provided even more
      distinct distributions in shorter times. It also accounts for multiconformer
      equilibria and provided realistic spectra and conformer distribution for the
      alanine.

PMID- 18816458
TI  - High-performance liquid chromatographic determination of creatine kinase activity
      influenced by methylglyoxal.
AB  - Protein glycation has been implicated in the development of diabetic
      complications and other health disorders, which mainly arise from accumulation of
      advanced glycation endproducts (AGEs) in vivo. Methylglyoxal (MGO), a typical
      reactive intermediate carbonyl formed in early glycation process, can react non
      enzymatically with N-terminal amino groups on proteins, leading to their
      inactivation and generation of detrimental AGEs. Recently, it was reported that
      activity of creatine kinase (CK, EC 2.7.3.2) could be reduced or even eliminated
      completely after incubation with MGO in vitro. CK activity is usually determined
      by conventional colorimetric assays. However, these methods are not appropriate
      for monitoring the influence of MGO on CK activity since MGO can also directly
      react with creatine, a substrate of CK. In this study, an efficient and much more
      accurate HPLC approach was established to investigate the effect of MGO on CK
      activity. Aminoguanidine was utilized to eliminate interference from the
      undesirable reaction between residual MGO and creatine. It was found that higher
      concentrations of MGO and longer incubation time for CK and MGO caused more
      pronounced reduction in CK activity. This HPLC method greatly facilitates
      acquisition of kinetic data about CK reaction and through further improvement it
      may be adopted to rapidly screen potential inhibitors of MGO-induced glycation.

PMID- 18816459
TI  - High-performance liquid chromatography determination of nitrated polycyclic
      aromatic hydrocarbons by indirect fluorescence detection.
AB  - A high-performance liquid chromatography (HPLC) method for the analysis of
      nitrated polcyclic aromatic hydrocarbons (NPAHs) is reported. NPAH mixtures were
      pre-concentrated using solid-phase extraction and well resolved on a C(18)
      column. They were detected using an indirect method involving the quenching of
      the emission from the fluorophores 5,6,7,8-tetrahydronaphthol (5,6,7,8-THN-1-OH),
      7-amino-4-methyl coumarin (Coumarin 120, COU-120) and 3-hydroxy-4-(2-hydroxy-4
      sulfo-1-naphthylazo)2-naphthalene carboxylic acid (Calcon carboxylic acid, CCA).
      Linear calibration curves were obtained in the range 1.1 x 10(-9) to 1.1 x 10(-8)
      mol/L. Using COU 120 as the fluorophore, the detection limit was 2.9 x 10(-10)
      mol/L for 1-nitronaphthalene and 2.1 x 10(-11) mol/L for 2-nitrofluorene.
      Recoveries of NPAHs from spiked tap water samples were between 88 and 100%.

PMID- 18816460
TI  - Conformational transitions of cyclic D,L-peptides.
AB  - Conformational transitions of cyclic D,L-hexapeptides have been studied by first
      principles calculations. Geometry optimizations for 20 types of homoresidue
      cyclic D,L-hexapeptide revealed that the cyclic peptides have two types of
      energetically stable backbone (extended (E) and bound (B) types); and for each
      type, the amino acid side chains have two orientations (equatorial and axial).
      Among the four types of isomer [E-type equatorial (E(eq)), B-type equatorial
      (B(eq)), E-type axial (E(ax)), and B-type axial (B(ax))], B(ax) is the
      energetically most preferred by most of the 20 encoded amino acid residues,
      whereas E(ax) is the least preferred. A search for transition states indicated
      that six types of conformational transition are possible between the isomers of
      the cyclic peptide, i.e., the backbone-backbone conversions (E(eq)-B(eq) and
      E(ax)-B(ax) transitions), the side chain-side chain conversions (E(eq)-E(ax) and
      B(eq)-B(ax) transitions), and the simultaneous conversions of the backbone and
      the side-chain orientation (E(eq)-B(ax) and E(ax)-B(eq) transitions). All the six
      transitions proceed with the breaking of the high molecular symmetry (S(6)) and
      go through the triangular (C(3)) intermediate structure with either equatorial or
      axial side-chain orientation.

PMID- 18816461
TI  - Quantitative determination of capsaicin, a transient receptor potential channel
      vanilloid 1 agonist, by liquid chromatography quadrupole ion trap mass
      spectrometry: evaluation of in vitro metabolic stability.
AB  - Capsaicin is the most abundant pungent molecule present in red peppers and it is
      widely used for food flavoring, in pepper spray in self-defense devices and more
      recently in ointments for the relief of neuropathic pain. Capsaicin is a
      selective agonist of transient receptor potential channel, vanilloid subfamily
      member 1. A selective and sensitive quantitative method for the determination of
      capsaicin by LC-ESI/MS/MS was developed. The method consisted of a protein
      precipitation extraction followed by analysis using liquid chromatography
      electrospray quadrupole ion trap mass spectrometry. The chromatographic
      separation was achieved using a 100 x 2 mm C(18) Waters Symmetry column combined
      with a gradient mobile phase composed of acetonitrile and 0.1% formic acid
      aqueous solution at a flow rate of 220 microL/min. The mass spectrometer was
      operating in full-scan MS/MS mode using two-segment analysis. An analytical range
      of 10-5000 ng/mL was used in the calibration curve constructed in rat plasma. The
      interbatch precision and accuracy observed were 6.5, 6.7, 5.3 and 101.2, 102.7,
      103.5% at 50, 500 and 5000 ng/mL, respectively. An in vitro metabolic stability
      study was performed in rat, dog and mouse liver microsomes and the novel
      analytical method was adapted and used to determine intrinsic clearance of
      capsaicin. Results suggest very rapid degradation with T(1/2) ranging from 2.3 to
      4.1 min and high clearance values suggesting that drug bioavailability will be
      considerably reduced, consequently affecting drug response and efficacy.

PMID- 18816462
TI  - Medicine utilisation review in selected non-governmental organisations primary
      healthcare clinics in the West Bank in Palestine.
AB  - BACKGROUND: Information on prescribing practices in Palestine is lacking,
      however, still essential for strategic planning. PURPOSE: To characterise
      prescribing patterns and specific medicine use indicators in selected non
      governmental organisations' (NGO) primary healthcare clinics/centres (PHC) in the
      West Bank (WB) in Palestine. METHODOLOGY: A prospective cross-sectional survey of
      prescribing practices based on medical records of 6032 patients with acute
      symptoms frequenting 41 NGO PHCs in the WB, between July and September 2004. A
      systematic random sample of every 10th patient appearing on the patient
      registration list was selected. Direct observation of consultation and dispensing
      practices and times in a sub-group of patients was completed utilising special
      forms. RESULTS: Respiratory tract infections were the most commonly occurring
      conditions. On average, 1.9 drugs were prescribed per encounter and antibiotics
      were the most commonly prescribed medications, followed by Analgesics and NSAIDs
      accounting for 46 and 20% of the total medications expenditures, respectively.
      Injections and combined medications use per encounter was 16 and 8%,
      respectively. Most commonly prescribed medications were of local production.
      Consultation (6.4 +/- 4.6 minutes) and dispensing times (1.6 +/- 1.5 minutes)
      were short with inadequate labelling. Provision of reference sources and
      treatment guidelines implementation were also inadequate. CONCLUSION: The results
      suggest that prescribing practices could be improved through wider implementation
      of treatment guidelines, a review of antibiotic prescribing, and increased time
      spent with patients to promote concordance. Strategies aimed at improving
      prescribing and dispensing practices should be addressed through new innovative
      capacity building models based on problem solving and feedback mechanisms.

PMID- 18816463
TI  - Truncation of small matrix elements based on the Euclidean norm for blocked data
      structures.
AB  - Methods for the removal of small symmetric matrix elements based on the Euclidean
      norm of the error matrix are presented in this article. In large scale Hartree
      Fock and Kohn-Sham calculations it is important to be able to enforce matrix
      sparsity while keeping errors under control. Truncation based on some unitary
      invariant norm allows for control of errors in the occupied subspace as described
      in (Rubensson et al. J Math Phys 49, 032103). The Euclidean norm is unitary
      invariant and does not grow intrinsically with system size and is thus suitable
      for error control in large scale calculations. The presented truncation schemes
      repetitively use the Lanczos method to compute the Euclidean norms of the error
      matrix candidates. Ritz value convergence patterns are utilized to reduce the
      total number of Lanczos iterations.

PMID- 18816464
TI  - Application of a lanthanide composite nanoparticle-sensitized luminescence method
      for the determination of salicylic acid in pharmaceutical formulations and human
      plasma.
AB  - Terbium-acetylacetone (Tb-acac) composite nanoparticles were synthesized using
      the ultrasonic method. The nanoparticles are water-soluble, stable and have
      extremely narrow emission bands and high internal quantum efficiencies. They were
      used as fluorimetric probes in the determination of salicylic acid (SA), based on
      the fluorescence enhancement of nanoparticles through fluorescence resonance
      energy transfer (FRET). The influence of buffer solution was investigated. Under
      the optimum conditions, a linear calibration graph was obtained over the SA
      concentration range 5 x 10(-7)-1 x 10(-4) mol/L. The limit of detection was found
      to be 2.5 x 10(-8) mol/L. The relative standard deviation (RSD) for six repeated
      measurements of 1 x 10(-4) mol/LSA was 1.75%. The method was applied to the
      determination of SA in pharmaceutical formulations and human plasma. We believe
      that the proposed approach has great potential for clinical purposes.

PMID- 18816466
TI  - Harnessing the interaction of ultrasound with tissue for therapeutic benefit:
      high-intensity focused ultrasound.

PMID- 18816468
TI  - Ultrasound: providing the physiological basis for fetal medicine.

PMID- 18816471
TI  - Semiquantitative study of tracheal fluid flow in a fetus with pulmonary
      hypoplasia: a possible prognostic factor?

PMID- 18816472
TI  - Abstracts of the 59th Annual Meeting of the American Association for the Study of
      Liver Diseases, 2008. October 31-November 4, 2008. San Francisco, California,
      USA.

PMID- 18816474
TI  - Immunochromatographic assay for the detection of pseudojujubogenin glycosides.
AB  - INTRODUCTION: Bacopa monnieri contains pseudojujubogenin glycosides as
      pharmacologically active compounds. In order to screen large numbers of plant
      samples for the presence of pseudojujubogenin glycosides, a rapid and simple
      assay system is required for application to small quantities of test materials.
      Immunoassays using monoclonal antibodies could be useful for the determination of
      small quantities of pseudojujubogenin glycosides in plant extracts. OBJECTIVE:
      The objective of this work was to develop a simple method for the detection of
      pseudojujubogenin glycosides by the immunochromatographic strip test using anti
      bacopaside I monoclonal antibody. METHODOLOGY: The qualitative assay was based on
      a competitive immunoassay in which the detector reagent consisted of a colloidal
      gold particle coated with the respective anti-bacopaside I MAb. The capture
      reagent was a bacopaside I-human serum albumin conjugate immobilised onto a test
      strip membrane. RESULTS: The sample containing pseudojujubogenin glycosides and
      the detection reagent were incubated with the immobilised capture reagent. The
      glycosides in the sample competed in binding to the limited amount of antibodies
      in the detection reagent with the immobilised bacopaside I-HSA conjugates and,
      hence, positive samples showed no colour in the capture spot zone. The detection
      limit for the strip test was 125 ng/mL. CONCLUSION: The assay system was found to
      be useful as a rapid and simple screening method for the detection of
      pseudojujubogenin glycosides in plants.

PMID- 18816476
TI  - Cervical length and maternal factors in expectantly managed prolonged pregnancy:
      prediction of onset of labor and mode of delivery.
AB  - OBJECTIVE: To examine the value of combining cervical length and maternal
      characteristics in a prolonged-pregnancy clinic in the prediction of the
      probability of firstly, spontaneous onset of labor within the subsequent 10 days
      and secondly, the need for Cesarean section. METHODS: This was a prospective
      study of women with singleton pregnancies attending an ultrasound-based prolonged
      pregnancy clinic at 40 + 4 to 41 + 6 weeks of gestation. The policy was to delay
      induction of labor by 7-10 days unless there was evidence of a specific medical
      or obstetric indication or the mother wanted earlier delivery. The measurement of
      cervical length was not given to the obstetrician, midwife or patient. Regression
      analysis was used to determine which of the following factors had a significant
      contribution in predicting induction of labor: maternal age, body mass index
      (BMI), ethnic origin, parity and cervical length. Regression analysis was also
      used to determine which of the factors amongst the maternal characteristics,
      onset of labor and cervical length provided significant prediction of Cesarean
      section. RESULTS: We examined 2316 pregnancies but we excluded from further
      analysis 452 (19.5%) cases because iatrogenic delivery was carried out within the
      subsequent 6 days, including 427 cases of induction of labor (340 at the request
      of the mother and 87 for medical indications) and 25 cases of Cesarean section.
      In the remaining 1864 cases there was spontaneous onset of labor and delivery
      within 10 days in 1536 (82.4%) and induction of labor in 7-10 days in 328
      (17.6%). The rate of Cesarean section was 15.2% (233 of 1536) in those with
      spontaneous onset of labor and 36.0% (118 of 328) in those whose labor was
      induced. Regression analysis demonstrated that in the prediction of induction of
      labor there were significant contributions from cervical length, BMI, parity and
      gestational age, and in the prediction of Cesarean section there were significant
      contributions from onset of labor, cervical length, BMI, parity and ethnicity.
      CONCLUSION: Ultrasonographic measurement of cervical length at 41 weeks together
      with maternal factors can define the patient-specific probability of spontaneous
      onset of labor in the subsequent week and the risk of Cesarean section.

PMID- 18816477
TI  - Butyl benzyl phthalate: effects on immune responses to ovalbumin in mice.
AB  - During recent decades the prevalence of IgE-mediated (atopic) allergic diseases
      in Western Europe and the USA has been increasing dramatically. It has been
      suggested that one possible cause is the presence in the environment of chemicals
      that may act as adjuvants, enhancing immune and allergic responses. Certain
      commonly used phthalate plasticizers such as butyl benzyl phthalate (BBP) have
      been implicated in this way. In the current experiments, the impact of BBP,
      applied by a physiologically relevant exposure route, on the vigour of immune
      responses induced in BALB/c strain mice has been examined. Mice were immunized
      via subcutaneous injection with the reference allergen ovalbumin (OVA) and
      received concurrent topical treatment with doses of BBP that induced significant
      changes in liver weight. The generation of specific anti-OVA IgE and IgG1
      antibodies was measured by passive cutaneous anaphylaxis and by enzyme-linked
      immunosorbant assays, respectively. Topical administration of BBP was without
      impact on anti-OVA IgE antibody responses, regardless of whether BBP was applied
      locally or distant to the site of OVA immunization. However, same-site treatment
      with high-dose BBP (100 mg) did result in a modest elevation in anti-OVA IgG1
      antibody production, a subclass of antibody used as a surrogate marker of IgE
      responses. Taken together with human exposure data, these results suggest that
      the doses of phthalate encountered in the home environment are unlikely to be a
      major factor contributing to the increased incidence of asthma and allergy in the
      developed world.

PMID- 18816478
TI  - Lipophilicity of some guaianolides isolated from two endemic subspecies of
      Amphoricarpos neumayeri (Asteraceae) from Montenegro.
AB  - In this study 10 guaianolide-type sesquiterpene gamma-lactones named
      amphoricarpolides, isolated from the aerial parts of two endemic subspecies of
      Amphoricarpos neumayeri (ssp. neumayeri and ssp. murbeckii Bosnjak), were
      investigated by means of reversed-phase thin-layer chromatography. Methanol-water
      and tetrahydrofuran-water binary mixtures were used as mobile phase in order to
      determine lipophilicity parameters R (0) (M) and C(0). Some of the investigated
      compounds were screened for their cytotoxic activity against HeLa and B16 cells.
      Chromatographically obtained lipophilicity parameters were correlated with
      calculated logP values and IC(50) values. Principal component analysis identified
      the dominant pattern in the chromatographically obtained data.

PMID- 18816479
TI  - Development of an immunochromatographic assay for rapid detection of 1
      Aminohydantoin in urine specimens.
AB  - A rapid immunochromatographic assay was developed and validated for detection of
      1-aminohydantoin (AHD) in urine specimens. Colloidal gold-labeled polyclonal
      antibody specific to AHD derivative was used as the marker; based on the
      competitive reactivity theory, the metabolite of nitrofurantoin after
      derivatization with benzaldehyde would compete with carboxyphenyl AHD derivative
      conjugated ovalbumin. The test strip could efficaciously detect the novel analyte
      with a visual detection limit of 10 ng mL(-1) and high specificity. The
      reliability of the assay was determined by testing 80 standard samples comparing
      with enzyme-linked immunosorbent assay. The semi-quantitative detection was
      accomplished in less than 15 min with low cost, especially for requirements of
      rapid and simple screening. This is the first publication of an
      immunochromatographic assay for detection of nitrofuran residues.

PMID- 18816480
TI  - Citicoline enhances frontal lobe bioenergetics as measured by phosphorus magnetic
      resonance spectroscopy.
AB  - Citicoline supplementation has been used to ameliorate memory disturbances in
      older people and those with Alzheimer's disease. This study used MRS to
      characterize the effects of citicoline on high-energy phosphate metabolites and
      constituents of membrane synthesis in the frontal lobe. Phosphorus ((31)P)
      metabolite data were acquired using a three-dimensional chemical-shift imaging
      protocol at 4 T from 16 healthy men and women (mean +/- SD age 47.3 +/- 5.4
      years) who orally self-administered 500 mg or 2000 mg Cognizin Citicoline (Kyowa
      Hakko Kogyo Co., Ltd, Ibaraki, Japan) for 6 weeks. Individual (31)P metabolites
      were quantified in the frontal lobe (anterior cingulate cortex) and a comparison
      region (parieto-occipital cortex). Significant increases in phosphocreatine
      (+7%), beta-nucleoside triphosphates (largely ATP in brain, +14%) and the ratio
      of phosphocreatine to inorganic phosphate (+32%), as well as significant changes
      in membrane phospholipids, were observed in the anterior cingulate cortex after 6
      weeks of citicoline treatment. These treatment-related alterations in phosphorus
      metabolites were not only regionally specific, but tended to be of greater
      magnitude in subjects who received the lower dose. These data show that
      citicoline improves frontal lobe bioenergetics and alters phospholipid membrane
      turnover. Citicoline supplementation may therefore help to mitigate cognitive
      declines associated with aging by increasing energy reserves and utilization, as
      well as increasing the amount of essential phospholipid membrane components
      needed to synthesize and maintain cell membranes.

PMID- 18816481
TI  - Dendrimer/DNA complexes encapsulated functional biodegradable polymer for
      substrate-mediated gene delivery.
AB  - BACKGROUND: To overcome the extracellular barriers in gene delivery and direct
      gene delivery to target tissues, substrate-mediated transfection, which sustains
      the release of naked DNA or vector/DNA complexes, and also supports cell growth,
      has been developed. METHODS: In the present study, polyamidoamine (PAMAM)
      dendrimer/DNA complexes encapsulated functional biodegradable polymer films for
      substrate-mediated gene delivery were prepared. To maintain the activity of DNA
      during dehydration, the dendrimer/DNA complexes were encapsulated in a water
      soluble polymer, poly alpha,beta-[N-(2-hydroxyethyl)-(L)-aspartamide], and then
      deposited on or sandwiched in functional polymer films with a fast degradation
      rate to mediate gene transfection. The in vitro gene transfections of pGL3-Luc
      and pEGFP-C1 plasmids in HEK293 cells mediated by different films were studied.
      For comparison, the transfection mediated by the film fabricated by conventional
      linear poly((DL)-lactide) was also investigated. RESULTS: The expression of pGL3
      Luc and pEGFP-C1 plasmids could effectively be mediated by the PAMAM/DNA
      complexes deposited or sandwiched polymer films, with transfection efficiencies
      comparable to that of solution-based transfections. The cells on the
      functionalized star poly((DL)-lactide) film exhibited much higher gene expression
      compared to the cells on the conventional linear poly((DL)-lactide) film because
      the fast degradation rate of star poly((DL)-lactide) facilitated the access of
      PAMAM/DNA complexes for the cells seeded on the film. In addition, the films did
      not exhibit any additional cytotoxicity to the cells during the degradation and
      transfection. CONCLUSIONS: The fast degrading functional polymer has great
      potential for localized transfection.

PMID- 18816482
TI  - Vaccination with a Modified Vaccinia Virus Ankara-based vaccine protects mice
      from allergic sensitization.
AB  - BACKGROUND: Currently, no treatment is available for food allergy and strict
      avoidance of the allergenic food remains the only way to manage the allergy. New
      strategies leading to a safe and efficacious food allergy treatment are required.
      Modified vaccinia virus Ankara (MVA), which allows high levels of expression of
      recombinant protein in vivo and gives rise to a Th1-biased specific immune
      response, was used as a prophylactic vaccine in a murine model of ovalbumin (OVA)
      allergy. METHODS: An MVA-OVA vector vaccine was prepared. Female BALB/c mice were
      vaccinated twice with a MVA-OVA vector vaccine, followed by sensitization with
      OVA plus alum. OVA-specific immunoglobulin E(IgE) activity was measured by
      mediator release from rat basophilic leukaemia cells, whereas specific IgG
      subclass titers were determined by enzyme-linked immunosorbent assay. RESULTS:
      Expression of immunological active OVA in mammalian cells was demonstrated. OVA
      specific IgE levels in sera from MVA-OVA-vaccinated mice were reduced and
      appeared delayed. The vaccine-mediated immune modulation was dose-dependent; the
      highest vaccine dose protected 50% of the animals from allergic sensitization.
      Upon sensitization, similar OVA-specific IgG1 titers were found in all mice, but
      the OVA-specific IgG2a antibody levels were strongly increased in MVA-OVA
      vaccinated mice, signifying a Th1-biased and, non-allergic immune response.
      CONCLUSIONS: Prophylactic vaccination with MVA-OVA delays and in part even
      prevents the onset of a successful allergen-specific sensitization. Recombinant
      MVA, which fulfills the requirements for clinical application, is a promising
      candidate vector for the development of novel approaches to allergen-specific
      prophylactic vaccination and specific immunotherapy.

PMID- 18816483
TI  - Targeting of interleukin-10 is superior to cytotoxic T-lymphocyte associated
      antigen 4 with human immunoglobulin G(1) for the prevention of chronic allograft
      deterioration in organ transplantation.
AB  - BACKGROUND: Genetic manipulation of the allograft is an attractive approach to
      prevent the graft against chronic deterioration through stable expression of
      immunomodulatory or protective genes. However, the best strategy for prevention
      of chronic allograft deterioration remains unclear. METHODS: The efficacies of
      adeno-associated viral vector-mediated stable expression of indoleamine 2,3
      dioxygenase (IDO), cytotoxic T-lymphocyte associated antigen 4 with human
      immunoglobulin G(1) (CTLA4Ig) or interleukin-10 (IL-10) in the prevention of
      chronic allograft deterioration were compared in a rat heart transplantation
      model. RESULTS: Transduction of grafts with IL-10 significantly prolonged
      allograft survival, whereas transduction of grafts with IDO did not improve graft
      survival compared to controls. Analysis of long-term survived heart allografts
      showed that both CTLA4Ig and IL-10 could significantly reduced the T cells and
      macrophage infiltration. However, stable expression of CTLA4Ig failed to prevent
      the development of transplant arteriosclerosis. By contrast, IL-10 suppressed the
      development of transplant arteriosclerosis effectively. The suppressive effects
      of IL-10 in preventing the development of chronic allograft deterioration were
      associated with lower transcript levels of transforming tumor growth factor beta
      1 and macrophage migration inhibitory factor in the graft. In addition, higher
      transcript levels of heme oxygenase-1 were found in IL-10-transduced allograft.
      CONCLUSIONS: Targeting on IL-10 is superior to CTLA4Ig or IDO for the treatment
      of chronic allograft deterioration.

PMID- 18816484
TI  - Involvement of glycosaminoglycans in vesicular stomatitis virus G glycoprotein
      pseudotyped lentiviral vector-mediated gene transfer into airway epithelial
      cells.
AB  - BACKGROUND: The involvement of surface molecules in HIV-1-derived lentivirus (LV)
      mediated transduction of airway epithelial cells has not been studied so far. The
      present study aimed to evaluate the role of glycosaminoglycans (GAGs) in gene
      transfer mediated by a third generation vesicular stomatitis virus G glycoprotein
      (VSV-G) pseudotyped LV vector in an in vitro model of polarized airway epithelial
      cells. METHODS: Human bronchial (16HBE-S1) and tracheal (CFT1-C2) epithelial
      cells were grown either on plastic or on filters and transduced with the LV
      vector polypurine tract (PPT)-green fluoresecent protein (GFP). Zonula Occludens
      (ZO)-1, a marker of tight junction, and GAG localization were assessed by
      cytofluorimetry and confocal microscopy. Soluble GAGs and removal of cell surface
      GAGs were used to affect LV-mediated transduction. RESULTS: Extensive
      optimization of experimental parameters (presence of polybrene during the
      infection, the incubation time in the presence of LV particles, period of time
      intercurring between infection and gene expression analysis) was carried out in
      plastic-adherent cells. Polybrene resulted to be cytotoxic and was not further
      used. In CFT1-C2 polarized cells, EGTA treatment determined a 20% decrease in
      transepithelial resistance, a diminished ZO-1 localization at the tight junction
      location and a 31% increase in GFP positive cells. Heparane sulfate was
      distributed evenly on the cell surface. Heparin and soluble chondroitin sulfate A
      and B inhibited LV-mediated transduction in a dose-dependent fashion. These
      results were confirmed upon enzymatic removal of GAGs from the cell surface.
      CONCLUSIONS: Taken together, these results show that GAGs are involved in VSV-G
      LV transduction of airway epithelial cells.

PMID- 18816485
TI  - Galactosylated multimodular lipoplexes for specific gene transfer into primary
      hepatocytes.
AB  - BACKGROUND: Numerous synthetic cationic vectors have been synthesized and are
      successfully used for in vitro gene transfer but an excess of positive charges
      can lead to cytotoxicity and does not enable specific transfection. METHODS: We
      decided to develop alternative molecular systems consisting of neutral,
      colloidally stable bioassemblies equipped with ligands for specific cell
      targeting. Consequently, we directed our efforts toward the development of a
      multimodular non-viral gene delivery system consisting of a condensed core of DNA
      with cationic liposomes of bis(guanidinium)-tren-cholesterol and an external
      corona of poly(ethylene oxide) stretches harbored by the steric stabilizers used
      to stabilize lipoplexes colloidally. A ligand capable of cell targeting by
      receptor-mediated endocytosis was covalently linked at the poly(ethylene oxide)
      extremity of steric stabilizers. Steric stabilizers were functionalized by a one
      step enzymatic galactosylation to develop new supramolecular assemblies of
      lipoplexes able to target asialoglycoprotein receptors located on primary
      hepatocytes. RESULTS: Cryo-TEM and fluorescence experiments showed that DNA was
      condensed within lamellar complexes whose size ranged between 100 to 300 nm in
      diameter. Bis(guanidinium)-tren-cholesterol-DNA lipoplexes, colloidally
      stabilized by galactosylated steric stabilizers at a galactosylated steric
      stabilizer/DNA ratio of 300, led to specific transfection of primary hepatocytes
      whereas ungalactosylated steric stabilizer did not transfect. CONCLUSIONS: Our
      findings confirm the receptor-mediated endocytosis pathway of galactosylated
      multimodular lipoplexes. Thus, we conclude that the fabrication of a multimodular
      assembly harboring a ligand without non-specific interaction with cell membranes
      is possible and a highly promising system to transfect other primary or cultured
      cells specifically through a receptor-dependent mechanism.

PMID- 18816486
TI  - Prevalence of scleroderma in Spain: an approach for estimating rare disease
      prevalence using a disease model.
AB  - PURPOSE: To estimate scleroderma prevalence in Spain. METHODS: As no data were
      available for Spain we used reported scleroderma incidence (Silman's study on UK
      and Alamanos' on Greece), scleroderma cause-specific mortality, obtained through
      the National Institute of Statistics (codes included in M34 of the International
      Classification of Diseases, 10th revision) in Spain and remission data. Estimates
      were applied to the Spanish population and to all-cause mortality for 2004,
      broken down by age group and gender. Estimators were assumed to follow a Poisson
      distribution. DisMod-II software was used for this purpose. RESULTS: Estimated
      prevalence was 0.23 and 0.71 cases per 10,000 people for men and women,
      respectively, based on UK incidence, and 0.28 and 2.58 cases per 10,000 people,
      respectively, based on Greek incidence. Estimated age at disease onset ranged
      from 50 to 58 years among men and from 52 to 55 among women, according to UK and
      Greek data, respectively. Mean duration of the disease was estimated to be in the
      range of 17-20 years for men and 19-20 for women. CONCLUSIONS: DisMod-II is
      useful for obtaining, modelling and confirming variability ranges of prevalence
      found in literature. It also provides information for orphan drug designation and
      for supporting public health decisions regarding rare diseases.

PMID- 18816487
TI  - Determination of bergenin in human plasma after oral administration by HPLC-MS/MS
      method and its pharmacokinetic study.
AB  - A highly sensitive, simple and selective high-performance liquid chromatography
      tandem mass spectrometry (HPLC-MS/MS) method was developed and applied to the
      determination of bergenin concentration in human plasma. Bergenin and the
      internal standard (IS) thiamphenicol in plasma were extracted with ethyl acetate,
      separated on a C(18 )reversed-phase column, eluted with mobile phase of
      acetonitrile-water, ionized by negative ion pneumatically assisted electrospray
      and detected in the multi-reaction monitoring mode using precursor --> product
      ions of m/z 327.1 --> 192 for bergenin and 354 --> 185.1 for the IS,
      respectively. The linear range of the calibration curve for bergenin was 0.25-60
      ng mL(-1), with the lowest limit of quantification of 0.25 ng mL(-1), and the
      intra/inter-day relative standard deviation (RSD) was less than 10%. The method
      is suitable for the determination of low bergenin concentration in human plasma
      after therapeutic oral doses, and has been first and successfully used for its
      pharmacokinetic studies in healthy Chinese volunteers.

PMID- 18816489
TI  - Travelling wave ion mobility mass spectrometry studies of protein structure:
      biological significance and comparison with X-ray crystallography and nuclear
      magnetic resonance spectroscopy measurements.
AB  - The three-dimensional conformation of a protein is central to its biological
      function. The characterisation of aspects of three-dimensional protein structure
      by mass spectrometry is an area of much interest as the gas-phase conformation,
      in many instances, can be related to that of the solution phase. Travelling wave
      ion mobility mass spectrometry (TWIMS) was used to investigate the biological
      significance of gas-phase protein structure. Protein standards were analysed by
      TWIMS under denaturing and near-physiological solvent conditions and cross
      sections estimated for the charge states observed. Estimates of collision cross
      sections were obtained with reference to known standards with published cross
      sections. Estimated cross-sections were compared with values from published X-ray
      crystallography and nuclear magnetic resonance (NMR) spectroscopy structures. The
      cross-section measured by ion mobility mass spectrometry varies with charge
      state, allowing the unfolding transition of proteins in the gas phase to be
      studied. Cross-sections estimated experimentally for proteins studied, for charge
      states most indicative of native structure, are in good agreement with
      measurements calculated from published X-ray and NMR structures. The relative
      stability of gas-phase structures has been investigated, for the proteins
      studied, based on their change in cross-section with increase in charge. These
      results illustrate that the TWIMS approach can provide data on three-dimensional
      protein structures of biological relevance.

PMID- 18816490
TI  - Observation of allicin-cysteine complex by reactive desorption electrospray
      ionization mass spectrometry for garlic.

PMID- 18816491
TI  - Transperineal versus transvaginal sonographic cervical length measurement in
      second- and third-trimester pregnancies.
AB  - OBJECTIVE: To investigate the reliability of, and patient satisfaction with,
      transperineal cervical length measurement during the third trimester of pregnancy
      and to compare these with measurement during the mid-trimester, using
      transvaginal sonographic imaging of the cervix as a reference. METHODS: Women
      attending an outpatient clinic for cervical length measurement before 29 weeks or
      after 35 weeks of gestation were examined by transvaginal and transperineal
      ultrasound and the results compared. Preference for either method was indicated
      by both sonographers and patients. RESULTS: Seventy-one patients participated in
      the study, 23 in the second and 48 in the third trimester of pregnancy. There was
      failure to obtain a clear image on transperineal ultrasound in 30% of mid
      trimester pregnancies, and in 19% of third-trimester cases. Elevation of the
      patient's hips improved the image in five out of 10 women in whom the scan was
      repeated following a postural change. Transvaginal cervical length measurements
      could be obtained in all cases. There was a strong correlation between
      transvaginal and transperineal measured cervical length (Pearson's correlation
      coefficient = 0.85). Sonographers preferred transvaginal images of the cervix
      irrespective of whether they were obtained in the second or third trimester.
      Transperineal ultrasound was judged as not or mildly painful by most women, but
      transvaginal ultrasound was preferred. CONCLUSIONS: Transvaginal ultrasound is
      the least painful, most feasible, and probably most accurate method with which to
      measure cervical length in the third trimester of pregnancy. Transperineal
      ultrasound is a feasible alternative, although its application in clinical
      practice is restricted by the need for an experienced sonographer.

PMID- 18816492
TI  - Low-dose aspirin reduces uteroplacental vascular impedance in early and mid
      gestation in IVF and ICSI patients: a randomized, placebo-controlled double-blind
      study.
AB  - OBJECTIVE: To determine whether low-dose aspirin improves uteroplacental
      hemodynamics in unselected in-vitro fertilization/intracytoplasmic sperm
      injection (IVF/ICSI) subjects when medication is started concomitantly with
      controlled ovarian hyperstimulation. METHODS: Thirty-seven pregnant women who had
      undergone IVF/ICSI and had been randomized to receive 100 mg aspirin (n = 17) or
      placebo (n = 20) daily, started concomitantly with controlled ovarian
      hyperstimulation, were included in this study. Doppler ultrasound examination was
      performed at 6, 10, 13 and 18 weeks' gestation. Uterine artery (UtA) pulsatility
      index (PI) was calculated and bilateral UtA notching was noted. Subplacental
      arcuate artery PI was obtained at 6 and 10 weeks' gestation. Umbilical artery
      (UA) PI and mean velocity were calculated at 10, 13 and 18 weeks' gestation. In
      the aspirin group there was one early pregnancy miscarriage, and one patient
      discontinued the study medication owing to early pregnancy bleeding. A total of
      15 women in the aspirin group and 20 women in the placebo group underwent the
      complete ultrasound protocol. RESULTS: At 6 weeks' gestation, arcuate artery PI
      and at 18 weeks' gestation, UtA PI were lower (P < 0.05) in the aspirin group
      than in the placebo group. At 18 weeks' gestation, bilateral UtA notching tended
      to be more common in the placebo group (40%) than in the aspirin group (13%) (P =
      0.06). UA PI and mean velocity did not differ significantly between the groups.
      CONCLUSION: Low-dose aspirin reduces uteroplacental vascular impedance in early
      and mid pregnancy in unselected IVF/ICSI subjects when medication is started
      concomitantly with controlled ovarian hyperstimulation.

PMID- 18816493
TI  - Maternal serum inhibin-A and activin-A levels in the first trimester of
      pregnancies developing pre-eclampsia.
AB  - OBJECTIVE: To evaluate whether measurement of maternal serum inhibin-A and
      activin-A at 11 + 0 to 13 + 6 weeks of gestation, alone or in combination with
      second-trimester uterine artery pulsatility measured by Doppler velocimetry, is
      useful in predicting those women who will develop pre-eclampsia. METHODS: This
      was a nested case-control study of pre-eclampsia cases with controls matched for
      gestational age and storage time for the maternal serum. Samples were collected
      as part of a first-trimester prenatal chromosomal anomaly screening program.
      Activin-A and inhibin-A were measured using a commercial enzyme-linked
      immunosorbent assay and the clinical outcomes were blinded to the operator. All
      the patients underwent uterine artery Doppler flow velocimetry to measure the
      mean pulsatility index at 22-24 weeks' gestation. RESULTS: In total there were 64
      cases with pre-eclampsia, with 34 delivering prior to 35 weeks of gestation. The
      control group included 240 cases. In the control group the levels of activin-A
      and inhibin-A did not change across the narrow gestational window and the median
      levels were 2.16 ng/mL and 231.13 pg/mL, respectively. In the pre-eclamptic group
      levels of activin-A and inhibin-A were significantly increased, at 2.52 ng/mL and
      286.64 pg/mL (1.24 multiples of the median (MoM) and 1.17 MoM, respectively).
      There was no difference in the median MoM in those delivering prior to 35 weeks
      and those delivering later. At cut-offs of the 90(th) centile of normal, activin
      A and inhibin-A levels would have identified 20% and 35%, respectively, of cases
      that would develop pre-eclampsia. When combined with uterine artery Doppler,
      activin-A measurement could have increased the detection rate from 55% to 63% and
      inhibin-A measurement could have increased it to 68% at a 5% false positive rate.
      CONCLUSION: Although increased in the first trimester, levels of activin-A and
      inhibin-A are probably too low to make a significant contribution to screening
      for pre-eclampsia at this time.

PMID- 18816494
TI  - Use of transvaginal ultrasonography to predict preterm birth in women with a
      history of preterm birth.
AB  - OBJECTIVE: To investigate whether cervical length measured by transvaginal
      ultrasonography predicts spontaneous preterm birth at < 35 weeks' gestation in
      women with a history of spontaneous preterm birth, stratified by spontaneous
      preterm birth history subtype (preterm premature rupture of membranes (PPROM) or
      preterm labor with intact membranes at onset of labor). METHODS: This
      retrospective cohort study included women with a history of spontaneous preterm
      birth that were subsequently pregnant with singleton gestations, compared with a
      low-risk control group. Transvaginal ultrasonographic cervical lengths were
      measured at 24 to 30 weeks of gestation. The primary outcome was spontaneous
      preterm birth at < 35 weeks. Secondary outcomes included spontaneous preterm
      birth at < 37 weeks and < 34 weeks, low birth weight, Cesarean delivery and
      perinatal morbidity and mortality. Multiple logistic regression analysis was used
      to control for potential confounders and calculate odds ratios and 95% confidence
      intervals. Receiver-operating characteristics (ROC) curves were used to determine
      the best cut-off for transvaginal ultrasound cervical length in predicting
      spontaneous preterm birth at < 35 weeks. RESULTS: Women with a history of
      spontaneous preterm birth with intact membranes at onset of labor (n = 42) had a
      shorter cervical length (3.28 cm) than women with a history of spontaneous
      preterm birth with PPROM at onset of labor (n = 48, cervical length 3.77 cm; P =
      0.019), and both subgroups had shorter cervical lengths than the low-risk control
      group (n = 103, cervical length 4.30 cm; P < 0.0001). Both subgroups were
      associated with spontaneous preterm birth at < 35 weeks, < 37 weeks, < 34 weeks
      and birth weight < 2500 g. ROC curves determined that the best cut-off for
      cervical length to predict spontaneous preterm birth at < 35 weeks was 3.0 cm. By
      multiple logistic regression analysis, the only independent predictors of
      spontaneous preterm birth at < 35 weeks were cervical length < 3.0 cm, a history
      of spontaneous preterm birth and antepartum bleeding in the current pregnancy. In
      women with a history of spontaneous preterm birth, a cervical length as measured
      by transvaginal ultrasonography of < 3.0 cm had a sensitivity of 63.6%,
      specificity of 77.2%, positive predictive value of 28.0% and negative predictive
      value of 93.8%, for preterm birth at < 35 weeks. CONCLUSION: Women with a history
      of spontaneous preterm birth with preterm labor and intact membranes at the onset
      of labor have shorter cervices than women with a history of spontaneous preterm
      birth and PPROM at the onset of labor, and both groups have shorter cervices than
      a low-risk control group. Both groups of women with a history of spontaneous
      preterm birth have an increased risk of recurrent spontaneous preterm birth at <
      35 weeks, and this is predicted by a transvaginal ultrasound cervical length of <
      3.0 cm.

PMID- 18816495
TI  - First-trimester screening in pregnancies conceived by assisted reproductive
      technology: significance of gestational dating by oocyte retrieval or sonographic
      measurement of crown-rump length.
AB  - OBJECTIVES: To evaluate, in pregnancies conceived by assisted reproductive
      technology, whether determination of gestational age (GA) by date of oocyte
      aspiration (DOA) or crown-rump length (CRL) at first-trimester screening
      influences the distribution of serum and sonographic markers or the performance
      of first-trimester screening for chromosomal abnormalities. METHODS: GA was
      calculated using either DOA or CRL at blood sampling and nuchal translucency
      thickness (NT) measurement in 729 singleton pregnancies conceived by in-vitro
      fertilization (IVF) or intracytoplasmic sperm injection (ICSI). Weight-corrected
      log multiples of the median (MoM) marker distributions specific for IVF pregnancy
      were established using multiple log regression and compared for DOA- and CRL
      based GA calculation. RESULTS: GA determined by CRL was significantly larger,
      albeit slightly, than was GA determined by DOA, with a mean difference of 1.50
      (SD, 2.4) days (P < 0.001). Log MoM distributions of free beta-human chorionic
      gonadotropin and NT showed that GA dating by CRL resulted in significantly
      higher, albeit slightly, mean log MoM values compared with DOA dating. The
      reverse was the case for mean log MoM pregnancy-associated plasma protein-A. The
      SDs were similar for CRL and DOA dating. According to Monte Carlo simulation, the
      use of DOA or CRL for GA dating did not appreciably influence the performance of
      first-trimester screening. CONCLUSIONS: DOA and CRL are practically equivalent
      when calculating GA for first-trimester screening. The correct method of GA
      dating for other purposes (e.g. estimated time of delivery) in IVF/ICSI
      pregnancies is still unresolved.

PMID- 18816496
TI  - Joint analysis of multiple longitudinal outcomes: application of a latent class
      model.
AB  - We address the problem of joint analysis of more than one series of longitudinal
      measurements. The typical way of approaching this problem is as a joint mixed
      effects model for the two outcomes. Apart from the large number of parameters
      needed to specify such a model, perhaps the biggest drawback of this approach is
      the difficulty in interpreting the results of the model, particularly when the
      main interest is in the relation between the two longitudinal outcomes. Here we
      propose an alternative approach to this problem. We use a latent class joint
      model for the longitudinal outcomes in order to reduce the dimensionality of the
      problem. We then use a two-stage estimation procedure to estimate the parameters
      in this model. In the first stage, the latent classes, their probabilities and
      the mean and covariance structure are estimated based on the longitudinal data of
      the first outcome. In the second stage, we study the relation between the latent
      classes and patient characteristics and the other outcome(s). We apply the method
      to data from 195 consecutive lung cancer patients in two outpatient clinics of
      lung diseases in The Hague, and we study the relation between denial and
      longitudinal health measures. Our approach clearly revealed an interesting
      phenomenon: although no difference between classes could be detected for
      objective measures of health, patients in classes representing higher levels of
      denial consistently scored significantly higher in subjective measures of health.

PMID- 18816497
TI  - Blood pressure estimation in the human fetal descending aorta.
AB  - OBJECTIVES: The objectives of this study were to estimate fetal blood pressure
      non-invasively from two-dimensional color Doppler-derived aortic blood flow and
      diameter waveforms, and to compare the results with invasively derived human
      fetal blood pressures available from the literature. METHODS: Aortic pressures
      were calculated from digitally recorded color Doppler cineloops of the fetal
      descending aorta by applying the Womersley model in combination with the two
      element Windkessel model, assuming constant pulse wave velocity during the second
      half of pregnancy. The results were compared with invasively derived human fetal
      blood pressures obtained from the literature. RESULTS: In 21 normal pregnancies
      the estimated mean aortic pressure regression line increased linearly from 28
      mmHg at 20 weeks of gestation to 45 mmHg at 40 weeks of gestation. The pulse
      pressure based on the regression line increased linearly from 21 mmHg at 20 weeks
      of gestation to 29 mmHg at 40 weeks of gestation. The aortic compliance exhibited
      a log linear relationship with the gestational age and a statistically
      significant eightfold increase was observed between 20 and 40 weeks. The aortic
      downstream peripheral resistance exhibited an exponentially decaying relationship
      across the same gestational age range. Non-invasively derived aortic systolic and
      diastolic aortic pressures were comparable with previously reported invasively
      derived systolic and diastolic umbilical arterial pressures; however, the mean
      pressures differed significantly from those reported in the umbilical artery in a
      separate study. The aortic systolic pressures calculated in this study were
      significantly higher than invasively derived left ventricular systolic pressures
      that have been previously reported in the literature. CONCLUSIONS: This study
      demonstrates the feasibility of estimating arterial blood pressure in the human
      fetus. The method described is of potential use in assessing fetal blood pressure
      non-invasively, particularly for studying relative changes with time.

PMID- 18816498
TI  - Re: Outcome of fetuses with antenatally diagnosed short femur.

PMID- 18816500
TI  - Fetal celiac and splenic artery flow velocity and pulsatility index: longitudinal
      reference ranges and evidence for vasodilation at a low portocaval pressure
      gradient.
AB  - OBJECTIVES: To establish longitudinal reference ranges for the fetal celiac and
      splenic arteries flow velocity and pulsatility index (PI), and to determine their
      hemodynamic relationship to venous liver perfusion and distribution and to other
      essential arteries. METHODS: This was a prospective longitudinal study of 161 low
      risk pregnancies. Doppler recordings of the celiac and splenic arteries were made
      on three to five occasions at 3-5-week intervals to establish reference ranges
      for blood velocity and PI measurements. Peak systolic velocity in the ductus
      venosus, a shunt between the umbilical and inferior caval veins, was used to
      represent the umbilicocaval (i.e. portocaval) pressure gradient, and the left
      portal vein blood velocity represented the umbilical distribution to the right
      liver lobe. The correlations between the celiac, splenic and hepatic arteries
      were determined, and their association with the middle cerebral and umbilical
      artery PIs (MCA-PI and UA-PI) was assessed. RESULTS: Longitudinal reference
      ranges for the fetal celiac and splenic arteries were established based on 510
      and 521 observations, respectively, during gestational weeks 21-39. Terms for
      calculating conditional reference ranges to be used for repeat observations are
      provided. Celiac and splenic artery PIs were low when portocaval pressure and
      umbilical supply to the right lobe were low (P < 0.0001). Their peak systolic
      velocity and PI were correlated (r = 0.7 (95% CI, 0.6-0.8) and r = 0.5 (95% CI,
      0.3-0.6), respectively), while the PI of the hepatic artery correlated weakly
      with those of the celiac and splenic arteries. They were positively associated
      with the MCA-PI and UA-PI (P < 0.0001). CONCLUSION: We provide longitudinal
      reference ranges for the fetal celiac and splenic arteries Doppler measurements
      and show that they are involved in maintaining portal liver perfusion
      independently from the hepatic artery.

PMID- 18816501
TI  - A comparison of three random effects approaches to analyze repeated bounded
      outcome scores with an application in a stroke revalidation study.
AB  - Discrete bounded outcome scores (BOS), i.e. discrete measurements that are
      restricted on a finite interval, often occur in practice. Examples are compliance
      measures, quality of life measures, etc. In this paper we examine three related
      random effects approaches to analyze longitudinal studies with a BOS as response:
      (1) a linear mixed effects (LM) model applied to a logistic transformed modified
      BOS; (2) a model assuming that the discrete BOS is a coarsened version of a
      latent random variable, which after a logistic-normal transformation, satisfies
      an LM model; and (3) a random effects probit model. We consider also the
      extension whereby the variability of the BOS is allowed to depend on covariates.
      The methods are contrasted using a simulation study and on a longitudinal
      project, which documents stroke rehabilitation in four European countries using
      measures of motor and functional recovery.

PMID- 18816502
TI  - Avoiding infinite estimates of time-dependent effects in small-sample survival
      studies.
AB  - We address the phenomenon of monotone likelihood in Cox regression with time
      dependent effects. Monotone likelihood occurs in the fitting process of a Cox
      model if at least one parameter estimate diverges to +/- infinity. We show that
      the probability of monotone likelihood is increased by the inclusion of time
      dependent effects, particularly in small samples with several unbalanced and
      highly predictive covariates, and with a high percentage of censoring. Firth's
      bias reduction procedure was shown to provide an ideal solution to monotone
      likelihood. Here we extend his idea to Cox regression with time-dependent
      effects. By penalized maximum likelihood estimation, finite hazard ratio
      estimates of constant and time-dependent effects can be obtained. Penalized
      likelihood ratio tests and profile penalized likelihood confidence intervals are
      proposed as tools for inference. A Monte Carlo study of Cox regression with time
      dependent effects confirms advantages of Firth-corrected (FC) over standard Cox
      analysis in terms of average bias and median absolute deviation. We also compare
      the FC and standard Cox approaches by means of analyses of two studies with time
      dependent effects. An SAS macro and an R package for FC Cox regression with time
      varying covariates and time-dependent effects are available at:
      http://www.muw.ac.at/msi/biometrie/programs.

PMID- 18816503
TI  - Hepatitis B and liver transplantation: 2008 update.
AB  - The ultimate goal of treatment is suppression of viral replication to
      undetectable HBV-DNA levels prior to and after liver transplantation (LT) to
      prevent infection of the newly transplanted liver. Most published data are
      available from therapy with lamivudine (LAM) in pre- and post-transplant HBV
      patients. Add-on therapy with adefovir dipivoxil (ADV) in pre-transplant LAM
      resistant patients has been shown to represent an effective antiviral strategy
      leading to hepatic recompensation in many cases and, eventually, removal from the
      waiting list. Newer nucleos(t)ide analogues such as entecavir, tenofovir and
      telbivudine have shown lower resistance rates than LAM and more antiviral potency
      in studies in the non-transplant setting. Combined hepatitis B immune globulin
      (HBIG) and nucleos(t)ide analogue therapy have been widely adopted as the most
      effective treatment strategy against recurrent HBV disease after LT. Many
      programs have evaluated lower doses or a shorter duration of HBIG and
      intramuscular versus intravenous routes of administration. Active immunisation
      using recombinant HBV vaccines, including the S, pre-S1 and pre-S2 regions, and
      those with immunostimulatory adjuvants, seem to be more immunogenic than the
      currently available vaccines and have been used in studies to replace HBIG.
      Furthermore, it has been shown that immune memory against HBV can be adoptively
      transferred from organ donors to transplant recipients. Nucleos(t)ide analogue
      combination therapies might provide an alternative to the current treatment
      paradigm with costly HBIG; however, experience with this new treatment regimen is
      very limited and controlled clinical studies are urgently warranted to
      investigate its safety and efficacy and to determine which nucleos(t)ide analogue
      combinations will be the most promising in the long term after LT.

PMID- 18816504
TI  - Quetiapine augmentation in depressed patients with partial response to
      antidepressants.
AB  - OBJECTIVE: Clinical trials suggest between 30-50% of depressed patients have an
      inadequate outcome to antidepressant pharmacotherapy. Among the approaches to
      improve outcome has been augmentation with antipsychotic medications. We aim to
      investigate the efficacy and tolerability of augmentation with quetiapine in
      depressed patients with a partial response to antidepressants. METHODS: Patients
      with a Major Depressive Disorder (DSMIV) who had partial/no response to a stable
      dose of an Selective Serotonin Reuptake Inhibitors (SSRI)/SNRI were recruited.
      All patients received add-on quetiapine (200-600 mg nocte) in a 6-week trial.
      Outcome measures (HAMD, MADRS) were assessed at screening, baseline, weeks 1, 2,
      4 and 6. Extrapyramidal symptoms (EPSEs) were assessed at baseline, weeks 2, 4
      and 6. A neuropsychological battery of tests was administered at baseline, weeks
      3 and 6. RESULTS: Nineteen patients entered the trial and 18 completed the trial
      per protocol. We report a rapid improvement in depression ratings over 6 weeks (p
      < 0.0005) and remission rates of 67% at week 1 and 94% at week 6. There was no
      evidence of EPSE and no worsening (and some improvement) of cognition.
      CONCLUSION: This suggests clinical benefits of quetiapine augmentation of
      SSRI/SNRI antidepressants with no worsening, and possible improvements in
      cognition.

PMID- 18816505
TI  - Simultaneous determination of mifepristone and monodemethyl-mifepristone in human
      plasma by liquid chromatography-tandem mass spectrometry method using
      levonorgestrel as an internal standard: application to a pharmacokinetic study.
AB  - A rapid and sensitive liquid chromatography/tandem mass spectrometry (LC-MS/MS)
      method was developed and validated to simultaneously determine mifepristone and
      monodemethyl-mifepristone in human plasma using levonorgestrel as the internal
      standard (IS). After solid-phase extraction of the plasma samples, mifepristone,
      monodemethyl-mifepristone and the IS were subjected to LC-MS/MS analysis using
      electro-spray ionization (ESI) in the multiple reaction monitoring (MRM) mode.
      Chromatographic separation was performed on an XTERRA MS C(18) column (150 x 2.1
      mm i.d., 5 microm). The method had a chromatographic run time of 4.5 min and
      linear calibration curves over the concentration ranges of 5-2000 ng/mL for
      mifepristone and monodemethyl-mifepristone. The recoveries of the method were
      found to be 94.5-103.7% for mifepristone and 70.7-77.3% for monodemethyl
      mifepristone. The method had a lower limit of quantification (LLOQ) of 5.0 ng/mL
      and a lower limit of detection (LOD) of 1.0 ng/mL for both mifepristone and
      monodemethyl-mifepristone. The intra- and inter-batch precision was less than 15%
      for all quality control samples at concentrations of 10, 100 and 1000 ng/mL.
      These results indicate that the method was efficient with a short run time (4.5
      min) and acceptable accuracy, precision and sensitivity. The validated LC-MS/MS
      method was successfully used in a pharmacokinetic study in healthy female
      volunteers after oral administration of 25 mg mifepristone tablet.

PMID- 18816506
TI  - Simultaneous determination of main taxoids in Taxus needles extracts by solid
      phase extraction-high-performance liquid chromatography with pentafluorophenyl
      column.
AB  - A simple and accurate RP-HPLC method with pentafluorophenyl (PFP) column was
      developed for the simultaneous determination of six taxoids, i.e. paclitaxel, 10
      deacetylbaccatin III (10-DAB III), 7-xylosyl-10-deacetyltaxol (7-xyl-10-DAT), 10
      deacetyltaxol (10-DAT), cephalomannine and 7-epi-10-deacetyltaxol (7-epi-10-DAT),
      in the extracts from the needles of three Taxus species. The mobile phase
      consisted of acetonitrile (A) and water (B), and the extracts were separated
      using gradient elution program: 30% A at the first 7 min, and then ramped to 42%
      A at 8 min, held until 38 min. The developed method was validated with
      satisfactory precision (RSD < 2.61%), repeatability (RSD < 2.92%) and recovery
      (95.19-104.47%). The above taxoids in the extracts of Taxus cuspidata, T.
      chinensis and T. media were analyzed with the developed RP-HPLC method, and the
      results showed that the contents of different taxoids in three mentioned species
      were distinct. Maximal amounts of 10-DAB III, 7-xyl-10-DAT and 7-epi-10-DAT
      appeared in T. chinensis, while T. media possessed the highest content of 10-DAT,
      cephalomannine and paclitaxel. The developed method is accurate and efficient. It
      can be reliably used in the improved determination of taxoids for the quality
      control of Taxus species.

PMID- 18816507
TI  - Determination of two metabolites of calycosin-7-O-beta-D-glucopyranoside in rat
      urine by HPLC.
AB  - A simple and specific analytical method for the simultaneous determination of the
      two metabolites of calycosin-7-O-beta-D-glucopyranoside, calycosin-7-O-beta-D
      glucuronic acid methyl ester (M-1) and calycosin (M-2), in rat urine was
      developed using high-performance liquid chromatography. Quercetin was employed as
      an internal standard. The correlation coefficients of the calibration curves were
      higher than 0.999; both intra- and inter-day precisions of two metabolites were
      determined and their RSD did not exceed 10%. The accuracy and linear range were
      investigated in detail. The cumulative urinary excretions of two metabolites were
      measured.

PMID- 18816508
TI  - Meta-analysis of diagnostic test studies using individual patient data and
      aggregate data.
AB  - A meta-analysis of diagnostic test studies provides evidence-based results
      regarding the accuracy of a particular test, and usually involves synthesizing
      aggregate data (AD) from each study, such as the 2 by 2 tables of diagnostic
      accuracy. A bivariate random-effects meta-analysis (BRMA) can appropriately
      synthesize these tables, and leads to clinical results, such as the summary
      sensitivity and specificity across studies. However, translating such results
      into practice may be limited by between-study heterogeneity and that they relate
      to some 'average' patient across studies.In this paper we describe how the meta
      analysis of individual patient data (IPD) from diagnostic studies can lead to
      clinical results more tailored to the individual patient. We develop IPD models
      that extend the BRMA framework to include study-level covariates, which help
      explain the between-study heterogeneity, and also patient-level covariates, which
      allow one to assess the effect of patient characteristics on test accuracy. We
      show how the inclusion of patient-level covariates requires a careful separation
      of within-study and across-study accuracy-covariate effects, as the latter are
      particularly prone to confounding. Our models are assessed through simulation and
      extended to allow IPD studies to be combined with AD studies, as IPD are not
      always available for all studies. Application is made to 23 studies assessing the
      accuracy of ear thermometers for diagnosing fever in children, with 16 IPD and 7
      AD studies. The models reveal that between-study heterogeneity is partly
      explained by the use of different measurement devices, but there is no evidence
      that being an infant modifies diagnostic accuracy.

PMID- 18816509
TI  - Computational studies on the backbone-dependent side-chain orientation induced by
      the (S,S)-CXC motif.
AB  - Disulfide cyclization is a well-known procedure to impose conformational
      restriction to peptides undergoing backbone flexibility. Rigid conformations are
      induced only for small rings with a specific combination of amino acids. In this
      work, we present a computational search of the backbone and backbone-dependent
      side-chain orientation of two series of linear and cyclic peptide analogs. The 
      C[XY]C- scaffold (where X,Y is arginine, aspartic acid or alanine residue) in its
      open and (S,S) cyclic form was used for the design of the studied analogs. Thirty
      six compounds, resulting from the extension with one residue at either the N- or
      the C-terminus were studied with classical MD. The local backbone conformation
      and the relative orientation of the X and Y side chains induced by either
      cyclization and/or the presence of the charged residues are discussed. From the
      present study it is concluded that cyclization has a great impact on the
      synplanar orientation of the X and Y side chains in the (S,S)Ac-XCYC-NH2 series
      of compounds while charge-charge interaction has only a weak synergic effect. On
      the contrary, the antiplanar orientation is favored in the case of (S,S)Ac-CXCY
      NH2.

PMID- 18816510
TI  - Curtailed two-stage designs in Phase II clinical trials.
AB  - When the accrual rate is low and the treatment period is long, a long
      observational period is required before information concerning the primary end
      point, such as binary response, becomes available in the study. Simon's two-stage
      designs are often employed in Phase II clinical trials to avoid giving patient an
      ineffective drug. Thus, if the new drug is ineffective then this design would
      certainly accelerate the process of drug discovery and development. However, for
      a promising new drug this design may still require a long observational period.
      Therefore, when drug safety is not a primary concern, this paper proposes
      curtailed two-stage designs to shorten the drug development process as soon as
      the treatment either shows lack of efficacy or is very effective. The proposed
      design is superior to Simon's two-stage designs in terms of savings in expected
      sample size and is much easier to implement in practice than stochastically
      curtailed Simon's designs.

PMID- 18816511
TI  - An R2 statistic for fixed effects in the linear mixed model.
AB  - Statisticians most often use the linear mixed model to analyze Gaussian
      longitudinal data. The value and familiarity of the R(2) statistic in the linear
      univariate model naturally creates great interest in extending it to the linear
      mixed model. We define and describe how to compute a model R(2) statistic for the
      linear mixed model by using only a single model. The proposed R(2) statistic
      measures multivariate association between the repeated outcomes and the fixed
      effects in the linear mixed model. The R(2) statistic arises as a 1-1 function of
      an appropriate F statistic for testing all fixed effects (except typically the
      intercept) in a full model. The statistic compares the full model with a null
      model with all fixed effects deleted (except typically the intercept) while
      retaining exactly the same covariance structure. Furthermore, the R(2) statistic
      leads immediately to a natural definition of a partial R(2) statistic. A mixed
      model in which ethnicity gives a very small p-value as a longitudinal predictor
      of blood pressure (BP) compellingly illustrates the value of the statistic. In
      sharp contrast to the extreme p-value, a very small R(2) , a measure of
      statistical and scientific importance, indicates that ethnicity has an almost
      negligible association with the repeated BP outcomes for the study.

PMID- 18816512
TI  - Evaluating the coupling efficiency of phosphorylated amino acids for SPOT
      synthesis.
AB  - A high demand of interest concerning binding assays to study the consequences of
      posttranscriptional phosphorylation may be addressed by peptide array-based
      methods. A crucial factor for de novo chemical approaches to generate such arrays
      is the possibility to rationally permutate phosphorylation events along a huge
      number of sequences. The simple principle behind this advantage is the stepwise
      synthesis of peptides, which allows the incorporation of either phosphorylated or
      nonphosphorylated derivates at serine, threonine, and tyrosine positions. In
      spite of several reported applications of phosphopeptide arrays, there is, to our
      best knowledge, no reported analysis of the efficiency of the involved
      techniques. Here, we analyze different coupling conditions to introduce
      phosphoamino acids in standard SPOT synthesis. Our results clearly indicate that
      EEDQ is the preferable activator and can also be used in fully automated SPOT
      synthesis.

PMID- 18816513
TI  - Peptaibiomics: towards a myriad of bioactive peptides containing C(alpha)
      dialkylamino acids?
AB  - Fungi are generally regarded as a literally infinite resource of bioactive
      secondary metabolites displaying remarkable structural diversity. Research on a
      particular group of linear and cyclic peptide antibiotics comprehensively named
      peptaibiotics--as result of the abundance of the non-proteinogenic C(alpha)
      dialkylated alpha-amino acids alpha-aminoisobutyric acid (Aib) and isovaline
      (Iva)--has been started 50 years ago. These peptides have gained constantly
      increasing interest because of their unique bioactivities and conformations. This
      review, reflecting the history of peptaibiotic research from 1958 to 2008, is
      focussed on introducing both the structural diversity and natural
      microheterogeneity of the peptaibiotics, as well as the biodiversity of their
      fungal producers. Recently introduced state-of-the-art methods for rapid
      screening and sequencing of peptaibiotics, such as peptaibiomics and intact-cell
      MALDI-TOF mass spectrometry, are discussed. Finally, future prospects in
      peptaibiotic research are presented. Owing to the ubiquity and biodiversity of
      the fungal producers in the biosphere, the discovery of a myriad of peptaibiotics
      within the next decade is predicted.

PMID- 18816514
TI  - {[1-(Arylmethyl)piperidin-4-yl]oxy}-(trifluoromethyl)-pyridines: ketanserin
      analogues with insect growth regulating activity.
AB  - A series of {[1-(arylmethyl)piperidin-4-yl]oxy}-(trifluoromethyl)-pyridine
      derivatives were designed and synthesized on the basis of the ketanserin (1)
      framework, a prototypic mammalian 5-HT(2A) receptor antagonist, and the structure
      activity relationship (SAR) was also discussed. The result of the bioassay showed
      that most of the title compounds inhibited the insect growth and exhibited
      moderate-to-good growth regulating activity against the armyworm Pseudaletia
      separata Walker. Furthermore, the SAR study revealed that, when the determinant
      feature, interacting with mammalian 5-HT(2A) receptor, was preserved, a
      simplified ArCH(2) group greatly contributed to insect growth inhibitory
      activities. It was also found that the substituted position of the CF(3) group at
      the pyridine ring played a key role, and that the introduction of 1-[bis(4
      fluorophenyl)methyl]piperazine, an equivalent of the benzoylpiperidine moiety of
      ketanserin, resulted in bioactivities similar to those of the title compounds,
      which were in agreement with the model of ketanserin analogues binding to
      mammalian 5-HT(2) receptors.

PMID- 18816515
TI  - Pentacyclic triterpenoids from the aerial parts of Lantana camara and their
      nematicidal activity.
AB  - Two new olean-12-ene triterpenoids, camarolic acid (1) and lantrigloylic acid
      (2), have been isolated from the aerial parts of Lantana camara, along with ten
      known triterpenes, namely, camaric acid, lantanolic acid, lantanilic acid,
      pomolic acid, camarinic acid, lantoic acid, camarin, lantacin, camarinin, and
      ursolic acid. The new compounds have been characterized as 3,25-epoxy-3alpha
      hydroxy-22beta-{[(S)-3-hydroxy-2-methylidenebutanoyl]oxy}olean-12-en-28-oic acid
      (1) and 3,25-epoxy-3alpha-hydroxy-22beta-[(3-methylbut-2-enoyl)oxy]olea-9(11),12
      dien-28-oic acid (2) through spectroscopic studies and a chemical transformation.
      Seven of the constituents, namely pomolic acid, lantanolic acid, lantoic acid,
      camarin, lantacin, camarinin, and ursolic acid, were tested for nematicidal
      activity against root-knot nematode Meloidogyne incognita. Pomolic acid,
      lantanolic acid, and lantoic acid showed 100% mortality at 1 mg/ml concentration
      after 24 h, while camarin, lantacin, camarinin, and ursolic acid exhibited 100%
      mortality at this concentration after 48 h. These results are comparable to those
      obtained with the conventional nematicide furadan (100% mortality at 1 mg/ml
      concentration after 24 h).

PMID- 18816516
TI  - The influence of the nitrogen substitution in three cytisine derivatives as
      ligands for the neuronal nAChRs: a structural and theoretical study.
AB  - Three cytisine derivatives, (-)-(7R,9S)-1-phenyl-3-(cytisin-12-yl)propan-1-one
      (1), (-)-(7R,9S)-1-phenyl-2-(cytisin-12-yl)ethane (2), and (-)-(7R,9S)-1,2
      bis(cytisin-12-yl)ethane (3), with different electronic and steric features have
      been characterized by X-ray analysis and theoretical calculations in order to
      evaluate how structural modulations affect the intrinsic binding affinity at the
      neuronal nicotinic receptors (nAChRs). The crystal structures of 1 and 2, which
      display comparable affinities, are characterized by the same conformation of the
      cytisine moiety with different orientations of the substituent at N2. In 3, two
      independent molecules have the pyridinone rings diversely oriented. This compound
      has a lower affinity with respect to 1 and 2, but it increases the expression of
      neuronal nAChRs. Compounds 1, 2, and 3 retain the key prerequisite of the
      classical pharmacophoric models, with sp(3)-N-atom--HBA distances close to the
      expected value, both in solid state and in solution (theoretical calculations),
      where, in contrast with the extended in the crystal state, a curled-up
      conformation has been found, though maintaining the N-substituent in equatorial
      position.

PMID- 18816517
TI  - Compounds from viburnum species and their biological activities.

PMID- 18816519
TI  - Marine drugs--macrolactins.
AB  - The increasing demands for new lead compounds in pharmaceutical and agrochemical
      industries have driven scientists to search for new bioactive natural products.
      Marine microorganisms are rich sources of novel, bioactive secondary metabolites,
      and have attracted much attention of chemists, pharmacologists, and molecular
      biologists. This mini-review mainly focuses on macrolactins, a group of 24
      membered lactone marine natural products, aiming at giving an overview on their
      sources, structures, biological activities, as well as their potential medical
      applications.

PMID- 18816520
TI  - Dendritic nucleotides: interaction with an aliphatic acid monolayer.
AB  - Dendrimeric-T and dendrimeric-A with 36 nucleotides were synthesized using
      phosphoramidite reagents. These dendrimers contain the nucleosides dA and dT,
      which are the components of the dA-dT base pair. Branching was obtained using a
      bifurcated and trifurcated reagent. The dendrimers were purified by ion-exchange
      chromatography. No specific interactions between these dendrimers were observed
      using atomic force microscopy. However, the dendrimeric-T is able to disrupt
      monolayers of fatty acids, resulting in a reorientation of the lipids (from head
      to-tail to head-to-head) as demonstrated by scanning tunneling microscopy (STM).

PMID- 18816521
TI  - Capnellenes from the soft coral Dendronephthya rubeola.
AB  - Four new acetoxycapnellenes 1-4, the first epoxyprecapnellene 5, along with the
      known dihydroxycapnellene 6 and monoacetoxycapnellene 7, have been isolated from
      the soft coral Dendronephthya rubeola. The structures were determined primarily
      by NMR spectroscopy. The compounds 6 and 7 showed a good antiproliferative
      activity against the cell line L-929 (murine fibroblasts) and a good cytotoxic
      activity against the HeLa (human cervix carcinoma) cell line. Compound 6 strongly
      inhibits the interaction of the oncogenic transcription factor Myc with its
      partner protein Max. Myc/Max-Interaction inhibitors are therapeutically
      interesting compounds in oncology.

PMID- 18816522
TI  - The production and characterisation of trichotoxin peptaibols, by Trichoderma
      asperellum.
AB  - Trichoderma spp. are regularly found as a constituent of the mycoflora of many
      soils and are noted for their antagonistic activity against bacteria and other
      fungi. This latter property is the basis for the widespread interest in their use
      in the biological control of soil-borne fungal plant pathogens. This antagonism
      is partly based on their ability to produce an impressive inventory of secondary
      metabolites. An important group of bioactive metabolites produced by Trichoderma
      spp. are the non-ribosomal peptides (NRPs), especially the peptaibols. A virulent
      antagonistic strain, T. asperellum, which had been used in biological control
      strategies in Malaysia and previously examined for mycolytic enzyme production,
      has been studied for its potential for peptaibol production. The present research
      demonstrated the ability of T. asperellum to produce at least two metabolites
      which were identified as acid trichotoxin 1704E (Ac-Aib-Gly-Aib-Leu-Aib-Gln-Aib
      Aib-Aib-Ala-Ala-Aib-Pro-Leu-Aib-Iva-Glu-Vol) and neutral trichotoxin 1717A (Ac
      Aib-Gly-Aib-Leu-Aib-Gln-Aib-Aib-Aib-Ala-Aib-Aib-Pro-Leu-Aib-Iva-Gln-Vol).
      Addition of free Aib to the culture medium enhanced the production of
      trichotoxins. Biological activity of these substances was investigated against
      Bacillus stearothermophilus. The general characteristics of peptaibols, also
      found in the trichotoxins, include the presence of high proportions of the
      uncommon amino acid Aib, the protection of the N- and C-termini by an acetyl
      group and reduction of the C-terminus to 2-amino alcohols, respectively,
      amphipathy and microheterogeneity.

PMID- 18816523
TI  - A recombination-based model for the origin and early evolution of genetic
      information.
AB  - Recombination is the exchange of groups of subunits between two entities. It is
      argued here that this process was central to the origin of life, because it
      allowed for the creation of useful information from a random pool of linear
      polymers. The length distribution of such a pool could be broadened if these
      polymers, such as RNA strands, have the capability of interacting and performing
      a cross-strand nucleophilic attack of a hydroxy group on a phosphate. Both the
      formation of stable secondary structures such as stem-loops and selection for
      self-replication can operate to push the equilibrium length distribution of the
      pool to longer and more catalytically proficient oligomers. There is empirical
      and theoretical support for these operations. Finally, in a collection of
      recombining linear oligomers, the advent of short recognition sequences that
      favor certain interactions over others, the property of a genotypic 'self' could
      develop, which later can shed its collective nature and be subject to Darwinian
      evolution. This could have given rise to true replicase enzymes, for example.

PMID- 18816524
TI  - Alkaloids from the roots of Zanthoxylum nitidum and their antiviral and
      antifungal effects.
AB  - Five alkaloids, 5,6-dihydro-6-methoxynitidine (1), dictamnine (2), gamma-fagarine
      (3), skimmianine (4), and 5-methoxydictamnine (5), were isolated from the roots
      of Zanthoxylum nitidum. Their structures and configurations were elucidated by
      spectroscopic methods and X-ray analysis. Compounds 1, 4, and 5 showed in vitro
      antiviral effect against hepatitis B virus, and compounds 2, 3, and 5
      demonstrated marked antimitotic and antifungal activity.

PMID- 18816525
TI  - Iridoid and aromatic glycosides from Scrophularia ningpoensis Hemsl. and their
      inhibition of [Ca2+](i) increase induced by KCl.
AB  - Bioassay-guided fractionation of EtOH extract of the roots of Scrophularia
      ningpoensis Hemsl. resulted in the isolation of three new iridoid glycosides,
      i.e., 6''-O-caffeoylharpagide (1), 6''-O-feruloylharpagide (2), and 6''-O-beta
      glucopyranosylharpagoside (3), and five new aromatic glycosides, i.e., 2-(3
      hydroxy-4-methoxyphenyl)ethyl O-alpha-arabinopyranosyl-(1-->6)-O-alpha
      rhamnopyranosyl-(1-->3)-O-beta-glucopyranoside (4), phenyl O-beta-xylopyranosyl
      (1-->6)-O-beta-glucopyranoside (5), 3-methylphenyl O-beta-xylopyranosyl-(1-->6)-O
      beta-glucopyranoside (6), 6-O-cinnamoyl beta-fructofuranosyl-(2-->1)-O-alpha
      glucopyranosyl-(6-->1)-O-alpha-glucopyranoside (7), and 6-O-feruloyl beta
      fructofuranosyl-(2-->1)-O-alpha-glucopyranosyl-(6-->1)-O-alpha-glucopyranoside
      (8), together with four known compounds, i.e., 6''-O-alpha-D-galactopyranosyl
      harpagoside (9), 6''-O-(p-coumaroyl) harpagide (10), harpagoside (11), and
      angoroside C (12). Activity of the isolated compounds on [Ca2+](i) increase
      induced by KCl was evaluated on rat cardiac myocytes using confocal laser
      scanning microscopy. Iridoid glycosides 1, 10, and 11, and aromatic glycosides 5
      and 6 significantly inhibited the increase of [Ca2+](i) induced by KCl at 100
      microM.

PMID- 18816526
TI  - Sesquiterpene Glucosides from Chloranthus japonicus Sieb.
AB  - A new lindenane sesquiterpene glucoside named yinxiancaoside A (1), a new, rare
      bidesmosidic megastigmane sesquiterpene glucoside named yinxiancaoside B (5), and
      three known sesquiterpene glucosides, chloranoside A (2), pisumionoside (3), and
      sarcaglaboside A (4), were isolated from the whole plant of Chloranthus japonicus
      Sieb. The structures of the new compounds were established by an extensive study
      of their spectral data, especially 1D- and 2D-NMR. The cytotoxic activity of the
      isolated compounds against human hepatoma (Hepg-2), human ovarian carcinoma
      (OV420), and human breast cancer (MCF-7) cells was investigated.

PMID- 18816527
TI  - Synthesis and cytotoxic evaluation of novel dimethyl [1,1'-biphenyl]-2,2'
      dicarboxylates bearing 1,3,4-thiadiazole moieties.
AB  - In search of novel anticancer agents, two series of dimethyl [1,1'-biphenyl]-2,2'
      dicarboxylate derivatives, 8a-8k and 9a-9k, containing both methylenedioxy and
      1,3,4-thiadiazole moieties were designed and synthesized. Cytotoxicity of these
      compounds was evaluated in vitro against five human tumor cell lines, i.e.,
      HepG2, KB, A549, K562, and MCF-7. The results indicated that 8h, 8j, 8k, 9d, 9g,
      9h, 9j, and 9k showed notable anticancer activities comparable to or stronger
      than that of 5-fluorouracil, a canonical anticancer drug. Structure-activity
      relationships were also discussed based on the experimental data obtained.

PMID- 18816528
TI  - Rat growth-hormone release stimulators from fenugreek seeds.
AB  - Bioassay-guided fractionation of MeOH extract from fenugreek (Trigonella foenum
      graecum L.) seeds resulted in the isolation of two rat growth-hormone release
      stimulators in vitro, fenugreek saponin I (1) and dioscin (9), along with two
      new, i.e., 2 and 3, and five known analogues, i.e., 4-8. The structures of the
      new steroidal saponins, fenugreek saponins I, II, and III (1-3, resp.), were
      determined as gitogenin 3-O-beta-D-xylopyranosyl-(1-->6)-beta-D-glucopyranoside,
      sarsasapogenin 3-O-beta-D-xylopyranosyl-(1-->6)-beta-D-glucopyranoside, and
      gitogenin 3-O-alpha-L-rhamnopyranosyl-(1-->2)-beta-D-glucopyranoside,
      respectively. Fenugreek saponin I (1) and dioscin (9) caused ca. 12.5- and 17.7
      fold stimulation of release, respectively, of rat growth hormone from rat
      pituitary cells, whereas gitogenin (5) showed moderate activity. To our
      knowledge, this is the first study to demonstrate that steroidal saponins
      stimulate rat growth-hormone release in rat pituitary cells.

PMID- 18816529
TI  - Pyridyl derivatives of benzaldehyde as potential antisickling agents.
AB  - Compounds that bind to sickle hemoglobin (Hb S) producing an allosteric shift to
      the high-affinity Hb S that does not polymerize are being developed to treat
      sickle cell anemia (SCA). In this study, three series of pyridyl derivatives of
      substituted benzaldehydes (Classes I-III) that combine structural features of two
      previously determined potent antisickling agents, vanillin and pyridoxal, were
      synthesized. When analyzed with normal human whole blood, the compounds form
      Schiff-base adducts with Hb and left shift the oxygen equilibrium curve (OEC) to
      the more soluble high-affinity Hb, more than vanillin or pyridoxal. Generally,
      Class-I compounds with an aromatic aldehyde located ortho to the pyridyl
      substituent are the most potent, followed by the Class-II compounds with the
      aldehyde at the meta-position. Class-III compounds with the aldehyde at the para
      position show the weakest activity. The structure-activity studies of these
      pyridyl derivatives of substituted benzaldehydes demonstrate significant
      allosteric potency that may be useful for treating SCA.

PMID- 18816530
TI  - Synthesis and biological evaluation of 4beta-[(4-substituted)-1,2,3-triazol-1
      yl]podophyllotoxins as potential anticancer agents.
AB  - A series of novel 4beta-[(4-substituted)-1,2,3-triazol-1-yl]podophyllotoxin
      derivatives were synthesized by employing Cu(I)-catalyzed click chemistry and
      evaluated for their anticancer activity against a panel of seven human cancer
      cell lines (HT-29, HCT-15, 502713, HOP-62, A-549, MCF-7, and SF-295). The
      compounds 9b, 9c, 9e, 9f, and 9h showed significant cytotoxic activities
      especially against HT-29, HCT-15, 502713 cell lines.

PMID- 18816531
TI  - Cytotoxicity of new stilbenoids from Pholidota chinensis and their spin-labeled
      derivatives.
AB  - Chemical investigation of the leave and stem of Pholidota chinensis Lindl has
      resulted in the isolation and characterization of three new stilbenoids. Their
      structures were established on the basis of spectroscopic evidence. A series of
      spin-labeled stilbene derivatives were synthesized. All of the new compounds were
      tested for cytotoxicity, and the results revealed that most of the spin-labeled
      stilbene derivatives showed superior cytotoxicity in vitro.

PMID- 18816532
TI  - Two cyathane-type diterpenoids from the liquid culture of Strobilurus tenacellus.
AB  - The structures of two new cyathane-type diterpenoids isolated from a liquid
      culture of Strobilurus tenacellus have been elucidated. The chemical structures
      of the new compounds 1 and 2 were identified as (12S)-11alpha,14alpha-epoxy
      13alpha,14beta,15-trihydroxycyath-3-ene and (12R)-11alpha,14alpha-epoxy
      13alpha,14beta,15-trihydroxycyath-3-ene, respectively, by spectral methods,
      including HR-EI-MS, and 1D- and 2D-NMR techniques. Compounds 1 and 2 show
      antimicrobial activity against Pseudomonas aeruginosa. In addition, both
      compounds were also tested for activity against human cancer cells, and 2 showed
      growth inhibitory activity against YMB and COLO 201 cells.

PMID- 18816533
TI  - Science in drug control: the alkaloid content of afghan opium.
AB  - Opium samples from Afghanistan were analyzed by HPLC for their content of
      morphine and three further alkaloids (codeine, thebaine, and papaverine). To our
      knowledge, this is the largest set of authentic opium samples analyzed in one
      study until now. The purpose was to assess possible correlations between samples
      and selected external factors, such as region of origin within Afghanistan, year
      of harvest, or intra-batch variation. In the investigated samples, a trend
      towards higher morphine concentrations in opium from the North-Eastern parts of
      Afghanistan was observed in the period from 2003 to 2005. More than 75% of the
      samples contained above 10% of morphine, the overall average was 14.4%.

PMID- 18816534
TI  - Chemical characterization of new oxylipins from Cestrum parqui, and their effects
      on seed germination and early seedling growth.
AB  - Isolation, chemical characterization, and phytotoxicity of five new oxylipins,
      together with seven already known related compounds, from Cestrum parqui L' Herl.
      is reported. All the structures were elucidated on the basis of their spectral
      data, especially 1D-(1H- and 13C-NMR, DEPT) and 2D-NMR (COSY, TOCSY, HSQC, HMBC,
      and NOESY). The configurations of the stereogenic C-atoms were determined by the
      Mosher's method. The compounds have been assayed for their phytotoxicity on
      Lactuca sativa at concentrations ranging between 10(-4) and 10(-8) M. The results
      of the phytotoxicity tests on the germination and growth of the test species,
      obtained by a cluster analysis, showed interesting relationship between the
      chemical structures of the compounds and their biological effects.

PMID- 18816535
TI  - Comparative photostability studies of BODIPY and fluorescein dyes by using
      fluorescence correlation spectroscopy.
AB  - In single-molecule applications, the photostability of fluorescent molecules is a
      key parameter. We apply fluorescence correlation spectroscopy to compare the
      photostability of four fluorescein and four borondipyrromethene (BODIPY) dyes of
      similar structure but different triplet yields. The latter class of dyes are more
      stable. In the kinetic analysis the, diffusion and photobleaching are treated as
      competitive processes. Corrections, which account for saturation and for
      experimental artefacts, are achieved solely by using experimental data.
      Photobleaching is found to occur mainly through the first excited singlet state
      S(1), in contrast to previous findings.

PMID- 18816536
TI  - Concerted and stepwise proton-coupled electron transfers in aquo/hydroxo complex
      couples in water: oxidative electrochemistry of [Os(II)(bpy)(2)(py)(OH(2))](2+).
AB  - Successive oxidation of transition metal(II) aqua complexes (M(II)OH(2) to
      M(III)OH) is a domain in which proton-coupled electron transfer reactions are
      extremely common. The mechanism of these PCET reactions-concerted or stepwise-is
      an important issue in the understanding and design of natural or artificial
      systems catalyzing the formation of dioxygen by four-electron oxidation of water.
      Concerted proton-coupled electron transfer from an aqua metal(II) to a hydroxo
      metal(III) complex requires the close proximity of a proton-accepting group with
      a pK value between those of the aqua complexes. Otherwise, stepwise electron
      proton or proton-electron pathways involving high-energy intermediates are
      followed. Concerted proton-electron pathways involving water as proton-acceptor
      or proton-donor group are inefficient. Cyclic voltammetry of the title complex in
      buffered aqueous solution and re-examination of previous results for the same
      complex attached to an electrode surface are used to establish these conclusions,
      which provide a starting point on the route to higher degrees of oxidation, such
      as those involved in the catalysis of water oxidation.

PMID- 18816537
TI  - Synthesis of aromatase inhibitors and dual aromatase steroid sulfatase inhibitors
      by linking an arylsulfamate motif to 4-(4H-1,2,4-triazol-4-ylamino)benzonitrile:
      SAR, crystal structures, in vitro and in vivo activities.
AB  - 4-(((4-Cyanophenyl)(4H-1,2,4-triazol-4-yl)amino)methyl)phenyl sulfamate (6 a) was
      the first dual aromatase-sulfatase inhibitor (DASI) reported. Several series of
      its derivatives with various linker systems between the steroid sulfatase (STS)
      and the aromatase inhibitory pharmacophores were synthesised and evaluated in JEG
      3 cells. The X-ray crystal structures of the aromatase inhibitors, DASI
      precursors 42 d and 60, and DASI 43 h were determined. Nearly all derivatives
      show improved in vitro aromatase inhibition over 6 a but decreased STS
      inhibition. The best aromatase inhibitor is 42 e (IC(50)=0.26 nM) and the best
      DASI is 43 e (IC(50 aromatase)=0.45 nM, IC(50 STS)=1200 nM). SAR for aromatase
      inhibition shows that compounds containing an alkylene- and thioether-based
      linker system are more potent than those that are ether-, sulfone-, or
      sulfonamide-based, and that the length of the linker has a limited effect on
      aromatase inhibition beyond two methylene units. Compounds 43 d-f were studied in
      vivo (10 mg kg(-1), single, p.o.). The most potent DASI is 43 e, which inhibited
      PMSG-induced plasma estradiol levels by 92 % and liver STS activity by 98 % 3 h
      after dosing. These results further strengthen the concept of designing and
      developing DASIs for potential treatment of hormone-related cancers.

PMID- 18816538
TI  - Diazoniapolycyclic ions inhibit the activity of topoisomerase I and the growth of
      certain tumor cell lines.

PMID- 18816539
TI  - Structures and solvatochromic phosphorescence of dicationic terpyridyl
      platinum(II) complexes with foldable oligo(ortho-phenyleneethynylene) bridging
      ligands.
AB  - A series of binuclear organoplatinum(II) complexes, [(tBu3tpy)Pt--(C[triple
      chemical bond]C--1,2-C6H4)n--C[triple chemical bond]C--Pt(tBu3tpy)][ClO4]2 (1-7,
      n=1, 2, 3, 4, 5, 6, 8; tBu3tpy=4,4',4''-tri-tert-butyl-2,2':6',2''-terpyridine)
      with foldable oligo(ortho-phenyleneethynylene) linkers were prepared and
      characterized by spectroscopic methods and/or X-ray crystallographic analyses. In
      the crystal structures of 32.5 CH3OH, 5CH3CN, and 64 CH3CN, each of the bridging
      ortho-phenyleneethynylene ligands has a partially folded conformation. In aerated
      water/acetonitrile mixtures with water percentages larger than 40 %, the emission
      of complexes 3-7 are red-shifted and enhanced when compared to those recorded in
      acetonitrile. The red-shift in emission energy and enhanced emission intensity
      can be attributed to the inter- and/or intramolecular interactions induced by the
      addition of water to solutions of the platinum(II) complexes in acetonitrile.
      Data from dynamic light scattering and transmission electron microscopy studies
      revealed that these binuclear platinum(II) complexes aggregated into nanosized
      particles in acetonitrile/water mixtures. Hydrophobic folding of the ortho
      phenyleneethynylene linkers in acetonitrile/water mixtures is postulated.

PMID- 18816540
TI  - A synthesis-driven structure revision of berkelic acid methyl ester.

PMID- 18816541
TI  - An efficient approach to substituted 1,5,7,8,9-pentahydrocyclopenta[h]-2
      benzopyran-3-one derivatives by a palladium-catalyzed tandem reaction of 2,7
      alkadiynylic carbonates with 2,3-allenoic acids.

PMID- 18816542
TI  - Synthesis of an energetic nitrate ester.

PMID- 18816543
TI  - Distinctly different reactivities of two similar polyoxoniobates with hydrogen
      peroxide.

PMID- 18816544
TI  - Engineering cytochrome P450 enzymes for improved activity towards biomimetic 1,4
      NADH cofactors.

PMID- 18816545
TI  - A simple cytosine to G-clamp nucleobase substitution enables chiral gamma-PNAs to
      invade mixed-sequence double-helical B-form DNA.

PMID- 18816546
TI  - A general and selective copper-catalyzed cross-coupling of tertiary Grignard
      reagents with azacyclic electrophiles.

PMID- 18816547
TI  - Formation mechanism of mesostructured silica in confined space: an in situ GISAXS
      study.
AB  - The structural evolution of periodic mesoporous material within the channels of
      anodic alumina membranes (AAMs) by evaporation-induced self-assembly (EISA) is
      investigated by a combination of in situ grazing-incidence small-angle X-ray
      scattering (GISAXS) with parallel detection of solvent evaporation and ex situ
      transmission electron microscopy (TEM). Kinetically controlled and equilibrium
      controlled structural evolution can be distinguished for these EISA processes. A
      new mechanism for formation of mesostructures in the confined environment of AAMs
      is proposed. Data are presented for samples synthesized with nonionic surfactants
      at various surfactant:silica ratios and relative humidities. The formation of and
      transformations between circular or columnar 2D hexagonal and tubular lamellar
      structures are observed. The circular hexagonal phase is kinetically favored over
      the columnar hexagonal orientation. The TEM images provide evidence that phase
      transformations, depending on their type, either start preferentially at the
      channel wall or in the center of the mesostructured fibers.

PMID- 18816548
TI  - Sonochemical synthesis under a magnetic field: fabrication of nickel and cobalt
      particles and variation of their physical properties.
AB  - We report on the variation of the physical properties of nickel and cobalt
      nanoparticles prepared by using ultrasound irradiation as energy source. First,
      we describe a sonochemical method for preparing aggregated particles. Second, we
      interpret the results on the basis of Einstein's theory (1905), which deals with
      a mathematical expression for the diffusivity of particles into solvents. This
      theory explains the stability of organosols of nickel and cobalt nanoparticles in
      polyethylene glycol. Finally, the effect of applying an external magnetic field
      during sonochemical formation of both aggregated particles and their stable
      colloids is investigated.

PMID- 18816549
TI  - Actinide polyoxometalates: incorporation of uranyl-peroxo in U-shaped 36-tungsto
      8-phosphate.

PMID- 18816550
TI  - Highly enantioselective hydrogenation of enol ester phosphonates: a versatile
      procedure for the preparation of chiral beta-hydroxyphosphonates.

PMID- 18816551
TI  - A general and environmentally benign catalytic reduction of nitriles to primary
      amines.

PMID- 18816552
TI  - A genetically encoded boronate-containing amino acid.

PMID- 18816553
TI  - Enantioselective synthesis of the carbocyclic D-ring subunit of massadine.

PMID- 18816554
TI  - Development of highly chemoselective bulky zincate complex, tBu4ZnLi2: design,
      structure, and practical applications in small-/macromolecular synthesis.
AB  - We present full details of the unique reactivities of the newly developed dianion
      type bulky zincate, dilithium tetra-tert-butylzincate (tBu(4)ZnLi(2)). With this
      reagent, halogen-zinc exchange reaction of variously functionalized haloaromatics
      and anionic polymerization of N-isopropylacrylamide (NIPAm)/styrene with
      excellent chemoselectivity were realized. Halogen-zinc exchange reaction followed
      by electrophilic trapping with propargyl bromide provided a convenient route to
      functionalized phenylallenes, particularly those with electrophilic functional
      groups (such as cyano, amide and halogens). Spectral and computational studies of
      the structure in the gas and liquid phases indicated extraordinary stabilization
      of this dianion-type zincate by its bulky ligands.

PMID- 18816555
TI  - Stannylated polynorbornenes as new reagents for a clean Stille reaction.
AB  - New functionalized polynorbornenes have been obtained in good yields by vinylic
      copolymerization of norbornene with a (norbornenyl)SnBu(2)Cl monomer, catalyzed
      by [Ni(C(6)F(5))(2)(SbPh(3))(2)]. Subsequent functionalization produces a wide
      variety of polymers with different --SnBu(2)R groups (R=aryl, vinyl, alkynyl).
      The polymers can be used as R-transfer reagents in Stille couplings, thereby
      providing easy workup and separation of the polymeric tin byproducts from the
      coupling products. Tin contents of around 0.05 wt % are found in the Stille
      products. The stannylated polymers can be recycled and reused with good
      efficiency.

PMID- 18816556
TI  - Models of the ox1 state of methylcoenzyme M reductase: where are the electrons?
AB  - The nature of the nickel center in the ox1 form of methylcoenzyme M reductase
      (MCR(ox1)), the enzyme that catalyzes the last step of biological methanogenesis,
      has long been controversial. A recent pulse electron paramagnetic resonance (EPR)
      study suggested a Ni(III)-thiolate, or equivalently a high-spin Ni(II) thiyl
      radical, description. The MCR(ox1) hyperfine parameters are best interpreted in
      terms of a Ni d(x(2)-y(2) ) SOMO, although a pure d(x(2)-y(2) ) SOMO does not
      explain the fact that about 7 % of the spin-density resides on the sulfur. The
      key goals of this DFT (PW91) study were to judge whether the Ni(III)-thiolate
      description is chemically sensible and, if so, to provide a detailed molecular
      orbital (MO) description of MCR(ox1). An Ni(III)-thiolate description was indeed
      found to be reasonable and was obtained as the ground state for symmetrized
      (C(s)) oxaporphyrin-, pyriporphyrin-, and isoporphyrin-based model complexes, as
      well as for a more realistic, biomimetic model. The model calculations yielded a
      number of insights, key among which are the following: 1) Although the SOMO
      topology may be viewed as d(x(2)-y(2) )-like, this MO also has a substantial
      amount of metal d(z(2) ) character, allowing it to overlap with a thiolate sigma
      lone pair, which would otherwise be orthogonal. 2) In one case (isoporphyrin), we
      were able to exploit the symmetry of the molecule to independently optimize the
      (d(x(2)-y(2) ))(1) and (d(z(2) ))(1) Ni(III) states, which turned out to be very
      close in energy. 3) The near-degeneracy of these two states provides an elegant
      explanation for the tendency of these two orbitals to hybridize. Admixture of
      substantial d(z(2) ) character into the d(x(2)-y(2) )-type SOMO of our most
      realistic model of MCR(ox1) results in a small but distinct spin population of
      about 0.04 on the sulfur, apparently nicely confirming the conclusions derived
      from the pulse EPR study. Other pure functionals also confirm this picture,
      although the hybrid functional B3LYP yields a spin-density profile that is
      clearly at odds with the EPR study.

PMID- 18816557
TI  - Protein nanotubes comprised of an alternate layer-by-layer assembly using a
      polycation as an electrostatic glue.
AB  - We present the synthesis and structure of various protein nanotubes comprised of
      an alternate layer-by-layer (LbL) assembly using a polycation as an electrostatic
      glue. The nanotubes were fabricated by sequential LbL depositions of positively
      charged polycations and negatively charged proteins into a porous polycarbonate
      (PC) membrane, followed by release of the cylindrical core by quick dissolution
      of the template with CH(2)Cl(2). This procedure provides a variety of protein
      nanotubes without interlayer cross-linking. The three-cycle depositions of poly-L
      arginine (PLA) and human serum albumin (HSA, M(w)=66.5 kDa) into the porous PC
      template (pore diameter, D(p)=400 nm) yielded well-defined (PLA/HSA)(3) nanotubes
      with an outer diameter of 419+/-29 nm and a wall thickness of 46+/-8 nm, revealed
      by scanning electron microscopy (SEM) and transmission electron microscopy (TEM)
      observations. The outer diameter of the tubules can be controlled by the pore
      size of the template (200-800 nm), whereas the wall thickness is always constant,
      independent of the D(p) value. The (PEI/HSA)(3) (PEI: polyethylenimine) nanotubes
      showed a slightly thin wall of 39+/-5 nm. CD spectra of the multilayered
      (PEI/HSA)(n) film on a flat quartz plate suggested that the secondary structure
      of HSA between the polycations was almost the same as that in aqueous solution.
      The three-cycle LbL depositions of PLA and ferritin (M(w)=460 kDa) or myoglobin
      (Mb, M(w)=1.7 kDa) into the porous PC membrane also gave cylindrical hollow
      structures. The wall thickness of the (PLA/ferritin)(3) and (PLA/Mb)(3) nanotubes
      were 55+/-5 nm and 31+/-4 nm; it depends on the globular size of the protein
      (ferritin>HSA>Mb). The individual ferritin molecule was clearly seen in the
      tubular walls by SEM and TEM measurements.

PMID- 18816558
TI  - Solvent-dependent changes in the triazolinedione-alkene ene reaction mechanism.
AB  - The influence of the solvent on the triazolinedione-alkene ene reaction mechanism
      has been investigated. Both inter- and intramolecular kinetic isotope effects
      with tetramethylethylenes and 2,2,2-(trideuterio)methyl-7-methyl-2,6-octadiene
      [D3]-1,1,1 provide, for the first time, strong evidence for changes in the
      mechanism of the reaction on going from non-protic to polar protic solvents. In
      non-protic polar or apolar solvents, an aziridinium imide that equilibrates to an
      insignificant extent with an open intermediate (a dipolar or a polarized
      biradical) is formed irreversibly in the first, rate-determining step of the
      reaction, which is followed by fast hydrogen abstraction. On the contrary, in
      polar protic solvents, hydrogen abstraction is rate limiting, allowing the main
      dipolar intermediate to equilibrate with its open intermediate(s) as well as with
      the starting reagents.

PMID- 18816559
TI  - Poly(p-phenylene ethynylene)s with facially amphiphilic pendant groups:
      solvatochromism and supramolecular assemblies.
AB  - Novel functionalized poly(p-phenylene ethynylene)s (PPEs) bearing facially
      amphiphilic cholic and deoxycholic acid units are synthesized by a Pd-catalyzed
      Sonogashira cross-coupling reaction. Some interesting properties, particularly
      their optical and self-assembly characteristics, are unraveled. The PPEs that
      carry bile acid substituents exhibit remarkable solvatochromism in a wide range
      of solvent systems, and judicious choice of the solvents can adjust the size and
      morphology of the formed nanoscale supramolecular aggregates. The incorporation
      of these naturally occurring building blocks can also impart biocompatibility to
      the conjugated system and stimulate the growth of living cells.

PMID- 18816560
TI  - Stereoconversion of amino acids and peptides in uryl-pendant binol schiff bases.
AB  - (S)-2-Hydroxy-2'-(3-phenyluryl-benzyl)-1,1'-binaphthyl-3-carboxaldehyde (1) forms
      Schiff bases with a wide range of nonderivatized amino acids, including unnatural
      ones. Multiple hydrogen bonds, including resonance-assisted ones, fix the whole
      orientation of the imine and provoke structural rigidity around the imine C==N
      bond. Due to the structural difference and the increase in acidity of the alpha
      proton of the amino acid, the imine formed with an L-amino acid (1-l-aa) is
      converted into the imine of the D-amino acid (1-D-aa), with a D/L ratio of more
      than 10 for most amino acids at equilibrium. N-terminal amino acids in dipeptides
      are also predominantly epimerized to the D form upon imine formation with 1.
      Density functional theory calculations show that 1-D-Ala is more stable than 1-L
      Ala by 1.64 kcal mol(-1), a value that is in qualitative agreement with the
      experimental result. Deuterium exchange of the alpha proton of alanine in the
      imine form was studied by (1)H NMR spectroscopy and the results support a
      stepwise mechanism in the L-into-D conversion rather than a concerted one; that
      is, deprotonation and protonation take place in a sequential manner. The
      deprotonation rate of L-Ala is approximately 16 times faster than that of D-Ala.
      The protonation step, however, appears to favor L-amino acid production, which
      prevents a much higher predominance of the D form in the imine. Receptor 1 and
      the predominantly D-form amino acid can be recovered from the imine by simple
      extraction under acidic conditions. Hence, 1 is a useful auxiliary to produce D
      amino acids of industrial interest by the conversion of naturally occurring L
      amino acids or relatively easily obtainable racemic amino acids.

PMID- 18816562
TI  - Investigation of a possible solvent cage effect in the reduction of 4
      aminocyclohexanone by a hydroxycyclopentadienyl ruthenium hydride.
AB  - No solvent cage effect could be found in the reduction of 4-aminocyclohexanone 3
      by Shvo's hydroxycyclopentadienyl ruthenium hydride 2. No preference was observed
      in the complex formation from trapping by aminoalcohol product 4 over external
      trapping by aminoketone 3 or by Shvo hydride 2. A solvent cage effect has
      previously been proposed to support an outer-sphere mechanism in the reduction of
      imines by 2; this was based on the observation that there was >90% preference for
      complexation of the newly formed amine over an external amine. Since alcohols
      form stronger hydrogen bonds than amines a larger cage effect would be expected
      in the present study. The lack of a cage effect in the present reduction suggests
      that the previous results from imine reduction require an additional explanation
      (other than a solvent cage effect).

PMID- 18816561
TI  - Switchable nanoassemblies from macroions and multivalent dye counterions.

PMID- 18816563
TI  - Why platinum catalysts involving ligands with large bite angle are so efficient
      in the allylation of amines: design of a highly active catalyst and comprehensive
      experimental and DFT study.
AB  - The platinum-catalyzed allylation of amines with allyl alcohols was studied
      experimentally and theoretically. The complexes [Pt(eta(3)-allyl)(dppe)]OTf (2)
      and [Pt(eta(3)-allyl)(DPP-Xantphos)]PF(6) (5) were synthesized and structurally
      characterized, and their reactivity toward amines was explored. The bicyclic
      aminopropyl complex [Pt(CH(2)CH(2)CH(2)NHBn-kappa-C,N)(dppe)]OTf (3) was obtained
      from the reaction of complex 2 with an excess of benzylamine, and this complex
      was shown to be a deactivated form of catalyst 2. On the other hand, reaction of
      complex 5 with benzylamine and allyl alcohol led to formation of the 16-VE
      platinum(0) complex [Pt(eta(2)-C(3)H(5)OH)(DPP-Xantphos)] (7), which was
      structurally characterized and appears to be a catalytic intermediate. A DFT
      study showed that the mechanism of the platinum-catalyzed allylation of amines
      with allyl alcohols differs from the palladium-catalyzed process, since it
      involves an associative ligand-exchange step involving formation of a
      tetracoordinate 18-VE complex. This DFT study also revealed that ligands with
      large bite angles disfavor the formation of platinum hydride complexes and
      therefore the formation of a bicyclic aminopropyl complex, which is a
      thermodynamic sink. Finally, a combination of 5 and a proton source was shown to
      efficiently catalyze the allylation of a broad variety of amines with allyl
      alcohols under mild conditions.

PMID- 18816564
TI  - Platinum(II) complexes with non-innocent ligands: solid-phase synthesis, redox
      chemistry and luminescence.

PMID- 18816565
TI  - Mechanism of the palladium-catalyzed carbohydroxylation of allene-substituted
      conjugated dienes: rationalization of the recently observed nucleophilic attack
      by water on a (pi-allyl)palladium intermediate.
AB  - The mechanism of the palladium-catalyzed oxidative carbohydroxylation of allene
      substituted 1,3-cyclohexadiene was studied by DFT calculations. All intermediates
      and transition states of the reaction were identified and their structures were
      calculated. The calculations confirm the mechanism previously proposed and show
      that the C--C bond-forming step occurs via insertion of one of the double bonds
      of 1,3-cyclohexadiene into a Pd--vinyl bond of a vinylpalladium intermediate.
      This reaction leads to a (pi-allyl)palladium intermediate, and coordination of
      benzoquinone and a double bond in the molecule to Pd creates a highly reactive
      cationic pi-allyl complex, which is readily attacked by water according to the
      calculations.

PMID- 18816566
TI  - Gold-film-catalysed hydrosilylation of alkynes by microwave-assisted, continuous
      flow organic synthesis (MACOS).
AB  - Thin gold films on the surface of glass capillaries have proven to be highly
      active catalysts for the rapid hydrosilylation of alkynes that are flowed through
      the reactor while being heated by microwave irradiation. The films are able to be
      reused at least five times with no loss of activity and with no detectable levels
      of gold showing up in the hydrosilylated products.

PMID- 18816567
TI  - Carbon pyramidalization in fullerene cages induced by the endohedral cluster: non
      scandium mixed metal nitride clusterfullerenes.

PMID- 18816568
TI  - Investigation of pH-dependent collagen triple-helix formation.

PMID- 18816569
TI  - Incorporating phosphaalkenes into oligoacetylenes.

PMID- 18816570
TI  - Dipositively charged protonated a3 and a2 ions: generation by fragmentation of
      [La(GGG)(CH3CN)2]3+.

PMID- 18816571
TI  - Stepwise cosensitization of nanocrystalline TiO2 films utilizing Al2O3 layers in
      dye-sensitized solar cells.

PMID- 18816572
TI  - A freight train of nanotubes for cargo transport on the nanoscale.

PMID- 18816573
TI  - DNA-assisted long-lived excimer formation in a cyclophane.

PMID- 18816574
TI  - A palladium-catalyzed dehydrogenative diamination of terminal olefins.

PMID- 18816579
TI  - Tactile devices to sense touch on a par with a human finger.
AB  - Our sense of touch enables us to recognize texture and shape and to grasp
      objects. The challenge in making an electronic skin which can emulate touch for
      applications such as a humanoid robot or minimally invasive and remote surgery is
      both in mimicking the (passive) mechanical properties of the dermis and the
      characteristics of the sensing mechanism, especially the intrinsic digital nature
      of neurons. Significant progress has been made towards developing an electronic
      skin by using a variety of materials and physical concepts, but the challenge of
      emulating the sense of touch remains. Recently, a nanodevice was developed that
      has achieved the resolution to decipher touch on a par with the human finger;
      this resolution is over an order of magnitude improvement on previous devices
      with a sensing area larger than 1 cm(2). With its robust mechanical properties,
      this new system represents an important step towards the realization of
      artificial touch.

PMID- 18816580
TI  - Competition between brand-name and generics--analysis on pricing of brand-name
      pharmaceutical.
AB  - The objective of this paper is to provide two-stage game models explaining the
      'Generic Competition Paradox' that demonstrates an increase of brand-name drug
      price in response to generic entry. Under the assumption that there are two
      groups of consumers who are segmented by their insurance status, high insurance
      coverage and low insurance coverage consumers, the models indicate that the
      decisive factor is the market share of the high insurance coverage consumer and
      the size of cross-substitute factor relative to certain characteristics of market
      demand. The paper analyses both the case of only true generic entry and the case
      of pseudo-generic and true generic entry. The models prove that a brand-name
      price will increase when both the market share of high insurance coverage
      consumer and the factor of cross-substitute are small. Also, the 'Generic
      Competition Paradox' more likely occurs in the market where less pseudo-generic
      products are produced.

PMID- 18816581
TI  - What has influenced patient health-care expenditures in Japan?: variables of age,
      death, length of stay, and medical care.
AB  - This study considers variables related to health-care expenditures associated
      with aging and long-term hospitalization in Japan. We focused on daily per capita
      inpatient health-care expenditures, and examined the impact of inpatient
      characteristics such as sex, age, survived or deceased, length of stay, adult
      disease, and type of medical care received during the duration of each stay. We
      analyzed data from the Survey of Medical-Care Activities in Public Health
      Insurance by multinomial logistic regression analyses. Age of patient had little
      impact on per capita inpatient health-care expenditures per day. As regards
      length of stay, inpatient stays of 8-14 days had a little impact on health-care
      expenditures. This study suggested that these results might be due to the kind of
      medical care received. More research is needed to determine the appropriate
      medical services to reduce long-term hospitalization. In the last month of care
      for patients who died, medical examinations had a great influence on health-care
      expenditures. This study showed that increasing medical examinations in the end
      of-life care needs further investigation.

PMID- 18816582
TI  - Why has the health inequality among infants in the US declined? Accounting for
      the shrinking gap.
AB  - Given that wealthier people are healthier, the increase in income inequality over
      the past two decades has led to fears that inequalities in health have also
      increased. Indeed, some papers have found that health disparities have become
      more salient among some adult populations. Using the US Vital Statistics 1983
      2000, this paper presents a new stylized fact: the infant health disparity, as
      measured by Apgar score, neonatal mortality and infant mortality, has been
      narrowing over the past two decades. This is in sharp contrast to the increasing
      disparities in health among adults of different educational backgrounds. Using a
      decomposition method, I find that the most important factor in explaining the
      closing gap is an increase in access to medical care. All else being equal,
      access to proper medical care is the most important factor in explaining the
      narrowing infant health gap. Demographic shifts and maternal behavior changes are
      also significant factors, together explaining 42.2% of the closing gap in low
      Apgar score, 41.4% of the closing gap in neonatal death, and 45.6% of the closing
      gap in infant death.

PMID- 18816583
TI  - Multivariate logit copula model with an application to dental data.
AB  - Applications of copulas for multivariate continuous data abound but there are
      only a few that treat multivariate binary data. In the present paper, we model
      multivariate binary data based on copulas using mixtures of max-infinitely
      divisible copulas, introduced by Joe and Hu (J. Multivar. Anal. 1996; 57(2): 240
      265). When applying copulas to binary data the marginal distributions also
      contribute to the dependence measures. We propose the use of covariate
      information in the copula parameters to obtain a direct effect of a covariate on
      dependence. To deal with model uncertainty due to selecting among several
      candidate models, we use a model averaging technique. We apply the model to data
      from the Signal-Tandmobiel dental study and, in particular, to four binary
      responses that refer to caries experience in the mandibular and maxillary left
      and right molars. We aim to model Kendall's tau associations between them, and
      examine how covariate information affects these associations. We found that there
      are systematically larger associations between the two mandibular and the two
      maxillary molars. Using covariates to model these associations more closely, we
      found that the systematic fluoride and age of the children affect the
      associations. Note that such relationships could not have been revealed by
      methods that focus on the marginal models.

PMID- 18816584
TI  - Studies on the molecular recognition between bioactive peptides and angiotensin
      converting enzyme.
AB  - High blood pressure or hypertension is a condition affecting many individuals and
      represents a controllable risk factor for cardiovascular diseases such as
      coronary heart disease and stroke. A non-pharmacological approach to manage these
      includes the application of food components with antihypertensive activity. Milk
      protein-derived peptides have been exploited as natural hypotensive agents,
      namely the peptides Val-Pro-Pro (VPP) and Ile-Pro-Pro (IPP), already
      commercialized in functional foods as a potential alternative to synthetic drugs.
      These bioactive peptides inhibit in vitro and in vivo the Angiotensin I
      converting enzyme (ACE), a protein with an important role in blood pressure
      regulation. In this work, we attempted to elucidate the possible mode of
      interaction between the peptides and ACE, including mechanisms of binding to the
      cofactor Zn2+, and further contrast this with the known mode of inhibition
      exerted by synthetic drugs (Captopril, Enalaprilat and Lisinopril). The bioactive
      peptide Ala-Leu-Pro-Met-His-Ile-Arg (ALPMHIR), also known to inhibit the enzyme
      ACE but with a lower efficiency than VPP and IPP, was utilized in the docking
      studies for comparison. It was observed that the best docking poses obtained for
      VPP and IPP were located at the ACE catalytic site with very high resemblance to
      the drugs mode of interaction, including the coordination with Zn2+. As for
      ALPMHIR, the best docking poses were located in the narrow ACE channel outside
      the catalytic site, representing higher affinity energies and fewer resemblances
      with the interaction established by drugs.

PMID- 18816585
TI  - Refined docking as a valuable tool for lead optimization: application to
      histamine H3 receptor antagonists.
AB  - Drug-discovery projects frequently employ structure-based information through
      protein modeling and ligand docking, and there is a plethora of reports relating
      successful use of them in virtual screening. Hit/lead optimization, which
      represents the next step and the longest for the medicinal chemist, is very
      rarely considered. This is not surprising because lead optimization is a much
      more complex task. Here, a homology model of the histamine H(3) receptor was
      built and tested for its ability to discriminate ligands above a defined
      threshold of affinity. In addition, drug safety is also evaluated during lead
      optimization, and "antitargets" are studied. So, we have used the same
      benchmarking procedure with the HERG channel and CYP2D6 enzyme, for which a
      minimal affinity is strongly desired. For targets and antitargets, we report here
      an accuracy as high as at least 70%, for ligands being classified above or below
      the chosen threshold. Such a good result is beyond what could have been
      predicted, especially, since our test conditions were particularly stringent.
      First, we measured the accuracy by means of AUC of ROC plots, i. e. considering
      both false positive and false negatives. Second, we used as datasets extensive
      chemical libraries (nearly a thousand ligands for H(3)). All molecules considered
      were true H(3) receptor ligands with moderate to high affinity (from microM to nM
      range). Third, the database is issued from concrete SAR (Bioprojet H(3) BF2.649
      library) and is not simply constituted by few active ligands buried in a chemical
      catalogue.

PMID- 18816586
TI  - Synthesis and studies on antidepressant and anticonvulsant activities of some 3
      (2-thienyl)pyrazoline derivatives.
AB  - In this study, the synthesis of twelve 3-(2-thienyl)pyrazoline derivatives are
      described. The structures of all compounds were confirmed by UV, IR, (1)H-NMR,
      mass spectral data, and microanalyses. In the pharmacological studies,
      antidepressant and anticonvulsant activities of these compounds have been
      screened. The antidepressant activities of the compounds were investigated by
      Porsolt's behavioral despair test (forced swimming) on albino mice and compared
      with tranylcypromine. Among the compounds examined, the compounds 9 and 12 showed
      significant antidepressant activity. Anticonvulsant activities of the compounds
      were determined by maximal electroshock seizure (MES) and subcutaneous
      pentylenetetrazole (metrazol) (scMet.) tests, neurotoxicities were determined by
      rotarod toxicity test on albino mice. Compound 8 was found to be protective
      against MES in the range of 30-300 mg/kg dose levels at four hours. None of the
      synthesized compounds showed neurotoxicity at 30-300 mg/kg dose levels.

PMID- 18816587
TI  - Synthesis and SAR study of T-type calcium channel blockers. Part II.
AB  - 3,4-Dihydroquinazoline derivatives have been known to be the novel and potent T
      type calcium channel blockers. From a systematic variation of 3,4
      dihydroquinazoline derivative 5c (KYS05043), plausible SAR results were
      established. It was revealed that a 5-(dimethylamino)pentylamino group at R(1), a
      biphenyl group at R(2), and a benzyl amido group at R(3)in the 3,4
      dihydroquinazoline backbone are closely related with the channel selectivity (T/N
      type) as well as the potency based on the discovery of 6k (KYS05090).

PMID- 18816588
TI  - 2-sulfonyliminodihydropyrimidines: a novel class of analgesic compounds.
AB  - A series of 2-sulfonyliminodihydropyrimidine derivatives have been synthesized
      and evaluated in vivo for their antinociceptive and anti-inflammatory activities.
      The results were compared with that of acetyl salicylic acid. Compounds 6Ab-d and
      6Be displayed an interesting analgesic profile in the acetic acid-induced
      abdominal contractions test. Based on the results of the carrageenan-hind paw
      edema test, compound 6Af showed potential anti-inflammatory activity.

PMID- 18816589
TI  - Synthesis and biochemical characterization of new phenothiazines and related
      drugs as MDR reversal agents.
AB  - Chemotherapy is one of the most important methods in the treatment of cancer.
      However, development of drug resistance during chemotherapy is the leading cause
      of treatment failure and decreased survival in cancer patients. Multidrug
      resistance (MDR) is one of the extensively studied forms of drug resistance for
      more than 30 years. The members of ATP-binding cassette protein family are
      responsible for multidrug resistance with P-glycoprotein as most representative
      transporter. To overcome multidrug resistance, pharmacological modulation of the
      transporters by efflux pump inhibitors seem to be the first choice, but
      preclinical studies did not lead to clinical applications. Therefore, a
      systematical research for pharmacophor structures is a promising strategy to
      increase the efficacy of those drugs still influencing multidrug resistance. In
      this study a range of phenothiazine derivatives was synthesizied with
      systematical variation of three molecule domains. The biochemical determination
      of multidrug resistance reversal activity was achieved with the crystalviolet
      assay on LLC-PK1/MDR1 cells. The results will be discussed considering of
      hypotheses in the literature directed to new structure-acitivity relationships to
      overcome drug resistance in the future.

PMID- 18816590
TI  - Convenient synthesis and antimicrobial activity of new 3-substituted 5
      (benzofuran-2-yl)-pyrazole derivatives.
AB  - The reaction of ethyl 4-(benzofuran-2-yl)-2,4-dioxobutanoate 2 with two moles of
      hydrazine hydrate afforded 5-(benzofuran-2-yl)-1H-pyrazole-3-carbohydrazide 4a,
      while its reaction with equimolar amount of phenylhydrazine gave ester 3b which
      then converted to 5-(benzofuran-2-yl)-1-phenyl-1H-pyrazole-3-carbohydrazide 4b.
      Various new compounds such as imides 5 and 6, acyl hydrazones 7 and 8, bi
      pyrazoles 9-12, and 1,3-thiazole derivatives 14 and 15 were prepared from
      carbohydrazide derivatives 4a, b. The new compounds are tested for their
      antimicrobial activity. Compounds 2, 5, 7, and 8 showed antifungal activities
      against C. albicans. Also, compounds 2, 6, 8, and 15 showed antibacterial
      activities.

PMID- 18816591
TI  - Clinical features of late-onset Pompe disease: a prospective cohort study.
AB  - The objective of this 12-month study was to describe the clinical features of
      late-onset Pompe disease and identify appropriate outcome measures for use in
      clinical trials. Assessments included quantitative muscle testing (QMT),
      functional activities (FAA), 6-min walk test (6MWT), and pulmonary function
      testing (PFT). Percent predicted values indicated quantifiable upper and lower
      extremity weakness, impaired walking ability, and respiratory muscle weakness.
      Significant declines in arm and leg strength and pulmonary function were observed
      during the study period. The outcome measures were demonstrated to be safe and
      reliable. Symptom duration was identified as the best predictor of the extent of
      skeletal and respiratory muscle weakness.

PMID- 18816592
TI  - Notice of duplicate publication.

PMID- 18816594
TI  - mrtl-A translation/localization regulatory protein encoded within the human c-myc
      locus and distributed throughout the endoplasmic and nucleoplasmic reticular
      network.
AB  - mrtl (myc-related translation/localization regulatory factor) is a previously
      uncharacterized protein synthesized from the first open reading frame contained
      within the human c-myc P0 transcript, approximately 800 nucleotides upstream of
      the Myc coding sequence. The mrtl protein, 114 amino acids in length, is
      projected to contain an N-terminal transmembrane domain and a highly charged C
      terminal interaction domain with homology to numerous RNA-binding proteins. Using
      monoclonal antibodies raised against the hydrophilic C-terminal domain,
      endogenous mrtl was visualized in human breast tumor cell lines and primary
      mammary epithelial cells at the nuclear envelope and contiguous
      endoplasmic/nucleoplasmic reticulum. mrtl colocalizes and coimmunoprecipitates
      with translation initiation factor eIF2alpha and the 40S ribosomal protein RACK1,
      and appears capable of binding specifically to the c-myc RNA. Inducible ectopic
      overexpression of wild-type mrtl interferes with the function of endogenous mrtl,
      which results in loss of Myc from the nucleus. Furthermore, treatment of cells
      with a peptide derived from the C-terminal domain displaces endogenous mrtl and
      causes a dramatic reduction in total cellular Myc protein levels. Together with
      our previous work demonstrating complete loss of tumorigenicity in association
      with ectopic expression of the c-myc P0 5'-UTR (containing the mrtl coding
      sequence), these results suggest that mrtl may serve an important function in
      regulating Myc translation and localization to the nucleus, perhaps ultimately
      contributing to the role of the c-myc locus in oncogenesis.

PMID- 18816596
TI  - Randomized trial to assess the efficacy of intraoperative steroid use in
      decreasing acute urinary retention after transperineal radioactive iodine-125
      implantation for prostate cancer.
AB  - BACKGROUND: Acute urinary retention is a potential complication of brachytherapy,
      with the literature estimating that 5% to 22% of patients require catheterization
      within 48 hours after implantation. In theory, postimplantation edema could be
      reduced by using intraoperative steroids. A prospective trial was conducted
      randomizing patients to a single intraoperative dose of dexamethasone versus no
      steroid use. METHODS: In all, 196 evaluable patients who received iodine-125
      (I(125)) interstitial brachytherapy alone as definitive treatment for low-to
      intermediate risk prostate cancer were randomized to receive either dexamethasone
      at a dose of 6 mg administered intravenously intraoperatively (Arm A) or no
      steroids (Arm B). All patients completed the International Prostate Symptom Score
      before treatment. Patients were contacted by telephone 72 to 96 hours after
      treatment and the need for catheterization was reported. RESULTS: Between 2003
      and 2005, 99 patients received steroids on treatment Arm A and 97 patients were
      treated according to control Arm B. Treatment arms were balanced with respect to
      pretreatment characteristics. A total of 3 patients required catheterization (2
      in Arm A and 1 in Arm B). The overall rate of catheterization was 1.5%, with no
      statistically significant difference noted between treatment arms. The 3 patients
      requiring catheterization had no statistical differences from other patients with
      respect to pretreatment characteristics, number of seeds/needles used, or
      postimplantation computed tomography volume of the prostate. CONCLUSIONS: There
      was no statistically significant difference noted between treatment arms in the
      current study, leading the authors to conclude that intraoperative dexamethasone
      did not decrease the rate of catheterization required after brachytherapy. The
      overall rate of postimplantation catheterization in the current study was 1.5%,
      which is lower than reported elsewhere in the literature and in a retrospective
      review from the study institution.

PMID- 18816597
TI  - Ultrafast optical pulse delivery with fibers for nonlinear microscopy.
AB  - Nonlinear microscopies including multiphoton excitation fluorescence microscopy
      and multiple-harmonic generation microscopy have recently gained popularity for
      cellular and tissue imaging. The optimization of these imaging methods for
      minimally invasive use requires optical fibers to conduct light into tight space,
      where free-space delivery is difficult. The delivery of high-peak power laser
      pulses with optical fibers is limited by dispersion resulting from nonlinear
      refractive index responses. In this article, we characterize a variety of
      commonly used optical fibers in terms of how they affect pulse profile and
      imaging performance of nonlinear microscopy; the following parameters are
      quantified: spectral bandwidth and temporal pulse width, two-photon excitation
      efficiency, and optical resolution. A theoretical explanation for the measured
      performance of these fibers is also provided.

PMID- 18816598
TI  - Morphological alterations of radicular dentine pretreated with different
      irrigating solutions and irradiated with 980-nm diode laser.
AB  - BACKGROUND: The topographical features of intraradicular dentine pretreated with
      sodium hypochlorite (NaOCl) or ethylenediamine tetraacetic acid (EDTA) followed
      by diode laser irradiation have not yet been determined. PURPOSE: To evaluate the
      alterations of dentine irradiated with 980-nm diode laser at different parameters
      after the surface treatment with NaOCl and EDTA. STUDY DESIGN: Roots of 60
      canines were biomechanically prepared and irrigated with NaOCl or EDTA. Groups
      were divided according to the laser parameters: 1.5 W/CW; 1.5 W/100 Hz; 3.0 W/CW;
      3.0 W/100 Hz and no irradiation (control). The roots were splited longitudinally
      and analyzed by scanning electron microscopy (SEM) in a quali-quatitative way.
      The scores were submitted to two-way Kruskal-Wallis and Dunn's tests. RESULTS:
      The statistical analysis demonstrated that the specimens treated only with NaOCl
      or EDTA (control groups) were statistically different (P < 0.05) from the laser
      irradiated specimens, regardless of the parameter setting. The specimens treated
      with NaOCl showed a laser-modified surface with smear layer, fissures, and no
      visible tubules. Those treated with EDTA and irradiated by laser presented
      absence of smear layer, tubules partially exposed and melting areas. CONCLUSIONS:
      The tested parameters of 980-nm diode laser promoted similar alterations on
      dentine morphology, dependent to the type of surface pretreatment.

PMID- 18816599
TI  - Epidermal glands in the abdomen of a basal ant Dinoponera lucida (Formicidae:
      Ponerinae).
AB  - The basal ant Dinoponera (Hymenoptera: Ponerinae) has lost the morphologic queen
      caste so that all females may be potential reproductive individuals, and the
      nestmate recognition results from cuticular hydrocarbons cues. However, data
      about the origin of that substance in Ponerinae ants are scarce. This study
      reports the occurrence of epidermal glands in the abdomen of the ant Dinoponera
      lucida. In this ant, the epidermis of the abdominal sternites has tall cells with
      well-developed nucleus contrasting with flattened and collapsed epidermis in the
      tergites, suggesting a glandular function in the epidermis of the sternites. The
      possible role of the glandular epidermis in the synthesis of cuticular
      hydrocarbons for the nestmate recognition is discussed.

PMID- 18816600
TI  - Sensory physiology assessed by evoked potentials in survivors of poliomyelitis.
AB  - Evidence suggests that sensory loss may occur in a proportion of patients
      affected by poliomyelitis. We hypothesize that sensory problems may be a lasting
      sequela in some polio survivors. Sensory pathways in polio survivors were
      evaluated clinically and electrophysiologically using sensory evoked potentials
      (SEPs). Patients with sensory deficits or abnormal SEPs were further evaluated by
      magnetic resonance imaging (MRI). Twenty-two patients were studied. The mean age
      was 64.7 years (age range: 56-81 years). Clinically, sensory impairments were
      found in 4 patients. Upper limb SEPs were normal. Lower limb SEPs were abnormal
      in 10 patients. In 1 patient, clinical and electrographic findings correlated
      with a patch of atrophy in the spinal cord, as shown by MRI. Sensory derangements
      may be found in a proportion of aging polio survivors. SEP studies may add
      sensitivity when evaluating sensory function in this cohort. It remains unclear
      whether these sensory abnormalities are related to remote poliomyelitis. Further
      studies are necessary.

PMID- 18816602
TI  - A novel LMNA gene mutation Leu162Pro and the associated clinical characteristics
      in a family with autosomal-dominant emery-dreifuss muscular dystrophy.
AB  - We report the clinical characteristics, genetic analysis, and muscle biopsy
      findings of a family with Emery-Dreifuss muscular dystrophy and a novel mutation
      (Leu162Pro) in the LMNA gene. Within this single family, the age of onset and
      disease severity varied among the family members. In addition, focal defects of
      nuclear membranes with chromatin blebs in endothelial cells was shown via
      electron microscopy.

PMID- 18816601
TI  - Adaptive and nonadaptive responses to voluntary wheel running by mdx mice.
AB  - The purpose of this study was to determine the extent to which hindlimb muscles
      of mdx mice adapt to a voluntary endurance type of exercise. mdx and C57BL mice
      engaged in 8 weeks of wheel running or maintained normal cage activities.
      Beneficial adaptations that occurred in mdx mice included changes in muscle mass,
      fiber size, and fiber types based on myosin heavy chain (MHC) isoform expression.
      These adaptations occurred without increases in fiber central nuclei and
      embryonic MHC expression. An undesirable outcome, however, was that muscle
      mitochondrial enzyme activities did not improve with exercise in mdx mice as they
      did in C57BL mice. Cellular remodeling of dystrophic muscle following exercise
      has not been studied adequately. In this study we found that some, but not all,
      of the expected adaptations occurred in mdx mouse muscle. We must better
      understand these (non)adaptations in order to inform individuals with DMD about
      the benefits of exercise.

PMID- 18816603
TI  - Collateral reinnervation by the superior laryngeal nerve after recurrent
      laryngeal nerve injury.
AB  - This study investigates the role of the intact superior laryngeal nerve (SLN) in
      the reinnervation process of one of the laryngeal muscles, the posterior
      cricoarytenoid muscle (PCA), following recurrent laryngeal nerve (RLN) injury.
      Using a chronic RLN injury model in the adult rat, PCA reinnervation was assessed
      by retrograde double-tracing techniques in combination with electrophysiology and
      immunohistochemistry of muscle sections. The results demonstrate that the PCA
      receives dual innervation from both laryngeal nerves even in the uninjured
      system. Functionally significant collateral reinnervation originates from intact
      SLN fibers following RLN injury, mainly due to intramuscular sprouting rather
      than by recruitment of more motor neurons. This may be important when choosing
      surgical and/or medical treatment for patients with RLN injury.

PMID- 18816604
TI  - Improvement with rituximab in a patient with both rheumatoid arthritis and
      myasthenia gravis.

PMID- 18816605
TI  - Epithelial and pseudoepithelial differentiation in glioblastoma and gliosarcoma:
      a comparative morphologic and molecular genetic study.
AB  - BACKGROUND: Glioblastomas exhibit a remarkable tendency toward morphologic
      diversity. Although rare, pseudoepithelial components (adenoid or epithelioid) or
      true epithelial differentiation may occur, posing a significant diagnostic
      challenge. METHODS: Hematoxylin and eosin-stained slides were reviewed, and
      immunohistochemistry and fluorescence in situ hybridization were performed.
      RESULTS: The patients included 38 men and 20 women. The median age at diagnosis
      was 57 years (interquartile range [IQR], 50 years-67 years), and the median
      overall survival was 7 months (IQR, 4 months-11 months). "Adenoid" glioblastomas
      (A-GBM) predominated (48%). True epithelial glioblastomas (TE-GBM) were next most
      frequent based on morphology and immunohistochemistry (35%), followed by
      epithelioid glioblastomas (E-GBM) (17%). Overall, 25 (43%) tumors featured a
      sarcomatous component. Molecular cytogenetic abnormalities identified by
      fluorescent in situ hybridization in A-GBM, E-GBM, and TE-GBM, respectively,
      included p16 deletion/-9 (60%, 71%, 64%); chromosome 10 loss (40%, 63%, 57%),
      chromosome 7 gain without EGFR amplification (70%, 38%, 40%), EGFR amplification
      (10%, 50%, 27%), PTEN deletion (10%, 25%, 29%), PDGFRA amplification (10%, 25%,
      0%), and RB1 deletion/-13q (50%, 0%, 14%). Abnormalities identified by
      immunohistochemistry included p21 immunonegativity (60%, 25%, 93%), which was
      most frequent in TE-GBM (P = .008), strong nuclear p53 staining (29%, 29%, 41%),
      strong membranous staining for epidermal growth factor receptor (EGFR) (21%, 63%,
      19%), which was most frequent in E-GBM (P = .03), and an increased frequency of
      p27 immunonegativity in gliosarcomas (15% negative, 85% focal) compared with
      tumors without sarcoma (38% strongly positive) (P = .009). CONCLUSIONS:
      Pseudoepithelial and true epithelial morphology are rare phenomena in GBM and may
      be associated with a similar poor prognosis. These tumors demonstrate proportions
      of molecular genetic abnormalities varying somewhat from conventional GBM.

PMID- 18816606
TI  - Preferential central nucleation of type 2 myofibers is an invariable feature of
      myotonic dystrophy type 2.
AB  - The clinical features of myotonic dystrophy type 1 (DM1) and type 2 (DM2) may
      present striking similarity, whereas, in some cases, the DM2 phenotype may be so
      mild that the diagnosis may be missed. Therefore, the identification of disease
      specific histopathological patterns for DM1 and DM2 may help clinicians to
      correctly address genetic studies. We performed a comparative morphological and
      morphometric analysis on muscle biopsies from 10 DM1 and 11 DM2 patients,
      comparing type 1 and type 2 fibers as to: fiber type predominance, transverse
      diameter, atrophy and hypertrophy factors, and prevalence of central nuclei. In
      DM1 cases we observed preferential type 1 fiber atrophy and a higher prevalence
      of central nucleation among type 1 fibers in all cases. In DM2 muscle biopsies,
      high rates of atrophic and hypertrophic type 2 fibers were observed in most
      cases, and preferential central nucleation in type 2 fibers was present in all
      cases. As opposed to DM1, in which type 1 fibers display most of the histological
      changes, preferential atrophy and hypertrophy of type 2 fibers may be considered
      as markers of DM2. A higher prevalence of central nuclei among hypertrophic type
      2 fibers has a predictive value for the diagnosis of DM2. Thus, morphometric and
      fiber type-based histological analysis of muscle biopsies may help differentiate
      between DM1 and DM2 and guide molecular analysis.

PMID- 18816607
TI  - Hepatocyte growth factor (HGF) and the satellite cell response following muscle
      lengthening contractions in humans.
AB  - The time-courses of satellite cell (SC) activation and protein expression of
      hepatocyte growth factor (HGF), HGF activator (HGFA), HGFA inhibitor-1 (HAI-1),
      and HGFA inhibitor-2 (HAI-2) in human skeletal muscle, as well as serum HGF
      following a single bout of muscle lengthening contractions, were determined.
      Eight recreationally active participants were recruited for the study. Subjects
      performed 300 lengthening contractions involving the quadriceps femoris muscles
      of a single leg at a fixed velocity of 180 degrees/s. Percutaneous muscle
      biopsies were taken before (PRE) and at 4 h (T4), 24 h (T24), 72 h (T72), and 120
      h (T120) following the exercise. The protocol resulted in an increase in the
      number of SCs [neural cell adhesion molecule (NCAM)-labeled cells] expressed
      relative to total myonuclei, at T24, compared with both PRE and T4 (P<0.05), and
      peaked at T72 (approximately 80% increase vs. PRE, P<0.05). HGF protein increased
      significantly in serum from baseline (PRE) to T4 (P<0.05). Active HGF protein was
      detected in skeletal muscle at rest [14.4+/-1.3 average integrated density value
      (IDV)/actin average IDV] and tended to increase at early time-points (P=0.12).
      HGFA protein increased significantly from PRE to T24 (P<0.05). HAI-1 protein
      increased significantly from PRE to T24 (P<0.05). HAI-2 (32 kDa) increased
      significantly from baseline (PRE) by T24 (P<0.05), and also by T72 and T120
      (P<0.05). We conclude that a single bout of lengthening muscle contractions is
      sufficient to activate SCs, which may involve both a local and systemic HGF
      response to contraction-induced injury.

PMID- 18816608
TI  - Substantial family history of prostate cancer in black men recruited for prostate
      cancer screening: results from the Prostate Cancer Risk Assessment Program.
AB  - BACKGROUND: Black men are at increased risk for prostate cancer (PCA),
      particularly with a family history (FH) of the disease. Previous reports have
      raised concern for suboptimal screening of black men with an FH of PCA. The
      extent of FH of PCA are reported from a prospective, longitudinal PCA screening
      program for high-risk men. METHODS: Black men ages 35 to 69 years are eligible
      for PCA screening through the Prostate Cancer Risk Assessment Program (PRAP)
      regardless of FH. Rates of self-reported FH of PCA, breast, and colon cancer at
      baseline were compared with an age-matched sample of black men from the 2005
      National Health Interview Survey (NHIS) using standard statistical methods.
      RESULTS: As of January 2007, 332 black men with pedigree information were
      enrolled in PRAP and FH of PCA was compared with 838 black men from the 2005
      NHIS. Black men in PRAP reported significantly more first-degree relatives with
      PCA compared with black men in the 2005 NHIS (34.3% [95% confidence interval (95%
      CI), 29.2-39.7] vs 5.7% [95% CI, 3.9-7.4]). Black men in PRAP also had more FH of
      breast cancer compared with those in the 2005 NHIS (11.5% [95% CI, 8.2-15.4] vs
      6.3% [95% CI, 4.6-8.0]). CONCLUSIONS: FH of PCA appears to be a motivating factor
      for black men seeking PCA screening. Targeted recruitment and education among
      black families should improve PCA screening rates. Efforts to recruit black men
      without an FH of PCA are also needed.

PMID- 18816609
TI  - Renal tumor ablation is a function of patient selection and technique--not the
      ablation technology.

PMID- 18816610
TI  - Long-term outcomes and clinicopathologic differences of African-American versus
      white patients treated with breast conservation therapy for early-stage breast
      cancer.
AB  - BACKGROUND: African-American (AA) and white patients with early-stage disease who
      were treated with breast conservation therapy (BCT) were examined to detect
      differences in clinicopathologic features and outcomes as a function of race.
      METHODS: Clinical data from the charts of 2164 white and 207 AA patients treated
      with BCT, and p53 expression status on 444 patients (from an existing tissue
      database), were analyzed to detect differences between the 2 cohorts. RESULTS:
      The median follow-up was 7 years. There were no differences in the method of
      tumor detection, lymph nodes excised, surgical margin status, or
      chemotherapy/radiotherapy delivered, reflecting similar screening and treatment
      policies for AA women in the study community. Despite this, AA patient presented
      at a younger age, with higher T and N classifications, and more estrogen and
      progesterone negative and "triple negative" tumors (all P values < .016). Tumors
      in AA patients were p53 positive more often than tumors in white patients (P=
      .0003). At 10 years, AA patients had a higher rate of distant metastasis (20% vs
      17%; P= .042), lymph node recurrence (6% vs 2%; P= .004), and breast recurrence
      (17% vs 13%; P= .036). There was no difference in overall survival between the 2
      groups. On multivariate analysis, only lymph node recurrence (risk ratio of
      3.140; 95% confidence interval, 1.396-7.063 [P= .0057]) remained significantly
      higher among AA women. CONCLUSIONS: In this cohort of uniformly treated patients,
      the authors found the expected clinicopathologic differences, but race was not
      found to be an independent predictor of local recurrence for AA patients when
      other confounding variables were taken into account in the multivariate model.
      These findings suggest that BCT is a reasonable option for appropriately selected
      AA patients. To the authors' knowledge, this is the largest study addressing
      outcomes after BCT for AA women published to date.

PMID- 18816611
TI  - American Association of Neuromuscular & Electrodiagnostic Medicine evidenced
      based review: use of surface electromyography in the diagnosis and study of
      neuromuscular disorders.
AB  - Surface electromyography (sEMG) measures myoelectrical signals recorded from
      sensors placed on the skin surface. The non-invasive nature of sEMG makes it a
      potentially useful technology for studying diseases of muscle and nerve. Reviews
      published by the American Association of Neuromuscular and Electrodiagnostic
      Medicine (AANEM) and the Therapeutics and Technology Assessment Subcommittee of
      the American Academy of Neurology (AAN), covering 1964-1994 and 1952-1998,
      respectively, concluded that sEMG adds no clinical utility over conventional
      needle EMG (nEMG) for the diagnosis of neuromuscular disease. The AANEM sEMG task
      force reevaluated the diagnostic utility and added value of this technology for
      the study of neuromuscular disease based on a contemporary review of relevant
      literature published between January 1994 and February 2006. The present review
      concludes that sEMG may be useful to detect the presence of neuromuscular disease
      (level C rating, class III data), but there are insufficient data to support its
      utility for distinguishing between neuropathic and myopathic conditions or for
      the diagnosis of specific neuromuscular diseases. sEMG may be useful for
      additional study of fatigue associated with post-poliomyelitis syndrome and
      electromechanical function in myotonic dystrophy (level C rating, class III
      data).

PMID- 18816612
TI  - Allograft inflammatory factor-1: a pathogenetic factor for vasculitic neuropathy.
AB  - Allograft inflammatory factor-1 (AIF-1) is a cytokine that plays a major role in
      the immune response and proliferative vasculopathy that occur during chronic
      allograft rejection. The purpose of this study was to characterize the cellular
      expression pattern and pathogenetic role of AIF-1 in nerve biopsies from patients
      with vasculitic neuropathy. We performed immunohistochemistry in human nerve
      biopsies of 10 patients with vasculitic neuropathies (VASs), 6 with chronic
      inflammatory demyelinating polyneuropathies (CIDPs), 5 with noninflammatory
      axonal neuropathies (NIANs), and 3 control nerves (CNs). In the CIDP and VAS
      nerves, AIF-1 expression was higher than in CN and NIAN nerves (P < 0.05). AIF-1
      was increased in the arterial walls of VAS compared with CIDP nerves (P < 0.05).
      Vascular smooth muscle cells in vasculitic nerve express AIF-1 at a higher level
      compared with CIDP and NIAN. AIF-1 plays a role in inflammatory nerve disease and
      vascular smooth muscle cell proliferation and may be a new molecular target for
      treatment.

PMID- 18816613
TI  - Long-term intensive electrically stimulated cycling by spinal cord-injured
      people: effect on muscle properties and their relation to power output.
AB  - Inactivity and muscular adaptations following spinal cord injury (SCI) result in
      secondary complications such as cardiovascular disease, obesity, and pressure
      sores. Functional electrically stimulated (FES) cycling can potentially reduce
      these complications, but previous studies have provided inconsistent results. We
      studied the effect of intensive long-term FES cycle training on muscle properties
      in 11 SCI subjects (mean +/- SEM: 41.8 +/- 2.3 years) who had trained for up to 1
      hour/day, 5 days/week, for 1 year. Comparative measurements were made in 10 able
      bodied (AB) subjects. Quadriceps maximal electrically stimulated torque increased
      fivefold (n = 5), but remained lower than in AB individuals. Relative force
      response at 1 HZ decreased, relaxation rate remained unchanged, and fatigue
      resistance improved significantly. Power output (PO) improved to a lesser extent
      than quadriceps torque and not to a greater extent than has been reported
      previously. We need to understand the factors that limit PO in order to maximize
      the benefits of FES cycling.

PMID- 18816614
TI  - Axial myoclonus in paraproteinemic polyneuropathy.
AB  - We describe a patient with a paraproteinemic anti-myelin-associated glycoprotein
      (anti-MAG) antibody polyneuropathy and concomitant axial myoclonic jerks.
      Neurophysiological investigation revealed that axial jerks were asymmetrical and
      exaggerated by lying in bed. They disappeared during mental arousal and sleep.
      Analysis of axial myoclonus showed that the first activated muscle was the left
      rectus abdominis with subsequent rostral and caudal propagation of a
      propriospinal type. Plasmapheresis substantially reduced the frequency and
      intensity of axial myoclonic jerks. In our patient, propriospinal myoclonus was
      associated with anti-MAG polyneuropathy, but the causal relationship remains
      unclear.

PMID- 18816618
TI  - Histologic associations and long-term cancer risk in columnar cell lesions of the
      breast: a retrospective cohort and a nested case-control study.
AB  - BACKGROUND: Mammary columnar cell lesions with atypia have been receiving
      increased scrutiny in view of their association with atypical hyperplasia (AH)
      and carcinoma. However, the few retrospective outcome studies performed have
      failed to establish an increased risk for recurrence or carcinoma on long-term
      follow-up. METHODS: The authors evaluated the overall cancer risk for 1261
      biopsies with columnar cell lesions (CCL) in 4569 women from the Nashville Breast
      Cohort who were biopsied between 1969 and 1988. On the basis of Schnitt and
      Vincent-Salomon's classification, they also classified 229 biopsies with CCL into
      3 categories: without hyperplasia or atypia, with hyperplasia lacking atypia, and
      with atypia. By using a nested case-control design, they compared the risks of
      invasive cancer associated with these 3 categories. RESULTS: A 2- to 3-fold
      increase in the occurrence of AH in the presence of CCL versus in their absence
      (P< .005) was observed. Relative risk of invasive breast cancer for women with
      both AH and CCL compared with those with AH alone did not differ significantly
      (risk ratio [RR]=1.55; P= .29). The presence of CCL alone was associated with a
      mild increase in the overall cancer risk (RR=1.47; P= .05). In the nested case
      control study, no significant risk difference was observed among the 3 categories
      of CCL. CONCLUSIONS: The authors observed a positive association between CCL and
      AH. The possibility that CCL by themselves significantly elevate breast cancer
      risk is not well supported. However, a finding of CCL on benign breast biopsy may
      indicate the presence of AH, a more worrisome lesion.

PMID- 18816619
TI  - Guideline implementation for breast healthcare in low-income and middle-income
      countries: overview of the Breast Health Global Initiative Global Summit 2007.
AB  - Breast cancer outcomes in low- and middle-income countries (LMCs) correlate with
      the degree to which 1) cancers are detected at early stages, 2) newly detected
      cancers can be diagnosed correctly, and 3) appropriately selected multimodality
      treatment can be provided properly in a timely fashion. The Breast Health Global
      Initiative (BHGI) invited international experts to review and revise previously
      developed BHGI resource-stratified guideline tables for early detection,
      diagnosis, treatment, and healthcare systems. Focus groups addressed specific
      issues in breast pathology, radiation therapy, and management of locally advanced
      disease. Process metrics were developed based on the priorities established in
      the guideline stratification. The groups indicated that cancer prevention through
      health behavior modification could influence breast cancer incidence in LMCs.
      Diagnosing breast cancer at earlier stages will reduce breast cancer mortality.
      Programs to promote breast self-awareness and clinical breast examination and
      resource-adapted mammographic screening are important early detection steps.
      Breast imaging, initially with ultrasound and, at higher resource levels with
      diagnostic mammography, improves preoperative diagnostic assessment and permits
      image-guided needle sampling. Multimodality therapy includes surgery, radiation,
      and systemic therapies. Government intervention is needed to address drug
      delivery problems relating to high cost and poor access. Guideline dissemination
      and implementation research plays a crucial role in improving care. Adaptation of
      technology is needed in LMCs, especially for breast imaging, pathology, radiation
      therapy, and systemic treatment. Curricula for education and training in LMCs
      should be developed, applied, and studied in LMC-based learning laboratories to
      aid information transfer of evidence-based BHGI guidelines.

PMID- 18816620
TI  - Cognitive impairment and cerebellar atrophy in typical onset 4Q35
      fascioscapulohumeral dystrophy.

PMID- 18816621
TI  - Withdrawal reflexes in adductor muscles elicited by electrical and magnetic
      stimulation of the obturator nerve.
AB  - The withdrawal reflex in the short head of the biceps femoris muscle after
      electrical stimulation of the sural nerve at the ankle has been investigated in
      numerous studies. These studies have described two distinct responses: early (R
      II) and late (R-III). However, withdrawal reflex activity of the adductor muscles
      in the legs has not been studied systematically. Adductor muscle reflex activity
      is important because it can produce serious clinical problems, such as adductor
      spasticity and spasms, during bladder surgery. The present study examined
      withdrawal reflex features of adductor muscles obtained by electrical and
      magnetic stimulation of the obturator nerve (ON) in 34 normal healthy subjects.
      Early adductor muscle withdrawal reflex responses were elicited by ipsilateral ON
      electrical stimulation with a mean latency of 45.7+/-2.0 ms (responses in 94% of
      subjects). Reflex responses were also obtained using magnetic stimulation at a
      similar incidence rate. Contralateral ON electrical stimulation resulted in a
      similar reflex, but with a lower incidence. ON and femoral nerve electrical and
      magnetic coil stimulation produced similar low-incidence responses in the vastus
      medialis. These findings indicate that short latency adductor withdrawal reflexes
      are easily obtained on both sides following electrical or magnetic stimulation of
      the ON, and they can be elicited by both nociceptive and nonnociceptive stimuli.
      These reflexes prepare the body for a proper response to incoming signals and
      likely serve to protect the pelvic floor and pelvic organs.

PMID- 18816622
TI  - Cetuximab in combination with carboplatin and docetaxel for patients with
      metastatic or advanced-stage nonsmall cell lung cancer: a multicenter phase 2
      study.
AB  - BACKGROUND: Cetuximab, an immunoglobulin (Ig) G1 chimeric monoclonal antibody
      against the epidermal growth factor receptor, has demonstrated evidence of
      activity in nonsmall cell lung cancer (NSCLC). When administered in combination
      with carboplatin and docetaxel, a commonly used regimen for advanced NSCLC,
      cetuximab has exhibited synergistic interaction in preclinical studies.
      Therefore, a phase 2 study was conducted to evaluate the efficacy of the
      combination of cetuximab, carboplatin, and docetaxel for the treatment of
      advanced NSCLC. METHODS: Chemotherapy-naive patients aged >or=18 years with stage
      IIIB (with effusion) or stage IV NSCLC received cetuximab (at a dose of 400
      mg/m(2) on Day 1 and 250 mg/m(2) on Days 8 and 15) plus docetaxel (at a dose of
      75 mg/m(2) on Day 1) and carboplatin (area under the concentration vs time curve
      [AUC]=6 on Day 1) every 21 days for up to 6 cycles (graded according to the
      American Joint Committee on Cancer Staging System). Thereafter, patients without
      evidence of disease progression were continued on single-agent cetuximab for a
      maximum of 1 year or until disease progression. The primary endpoint was response
      rate. RESULTS: Eighty patients were enrolled. The median number of cycles
      administered was 4 (range, 1-6 cycles). The objective response rate was 15.2%,
      with a median progression-free survival of 4.6 months and a median overall
      survival of 10.3 months. The salient grades 3 of 4 adverse events were
      neutropenia (30%), hypotension (3%), hypokalemia (4%), and hypomagnesemia (3%).
      Twenty-five patients received single-agent cetuximab (median duration, 12 weeks)
      and this was well tolerated. CONCLUSIONS: The results of this large, multicenter,
      phase 3 study indicate that the novel combination of cetuximab with docetaxel and
      carboplatin demonstrate modest anticancer activity for patients with advanced and
      metastatic NSCLC and has an acceptable toxicity profile.

PMID- 18816623
TI  - Comparison of parametric and nonparametric reference data in motor unit potential
      analysis.
AB  - For calculation of outlier reference intervals, by definition nonparametric
      statistics are applied, while for mean value reference intervals parametric or
      nonparametric statistics can be used. The aim of this study was to compare the
      mean value reference intervals and their sensitivity for diagnosis of myopathy.
      Quantitative concentric needle electromyography (EMG) of the biceps brachii
      muscle was performed using multi-motor unit potential (MUP) analysis. In 34
      healthy subjects both parametric (mean+/-2SD) and nonparametric (2.5th-97.5th
      percentiles) reference intervals were calculated for mean values of MUP
      parameters, while for outliers nonparametric reference intervals (5th-95th
      percentiles) were calculated. Their sensitivity was tested in 29 patients with
      facioscapulohumeral muscular dystrophy. Nonparametric reference intervals were
      narrower than parametric intervals, which resulted in slightly higher
      sensitivities when combined with outlier limits (e.g., thickness=86% and 83%,
      respectively).

PMID- 18816625
TI  - Location of collateral sprouting of donor nerve following end-to-side
      neurorrhaphy.
AB  - Various studies have demonstrated collateral regeneration of the donor nerve
      following end-to-side neurorrhaphy, but the location of collateral sprouting
      remains controversial. In a rat end-to-side neurorrhaphy model we isolated nerve
      fibers from the donor nerve at the neurorrhaphy site utilizing a micro-tease
      technique. We found that axons sprouted collaterally from a myelinated nerve
      fiber at the node of Ranvier. Based on this preliminary result we conclude that
      myelinated nerve fibers could sprout collateral branches at the node of Ranvier
      at an end-to-side neurorrhaphy site. These findings show that end-to-side
      neurorrhaphy may be an alternative for peripheral nerve repair.

PMID- 18816624
TI  - Cryoablation or radiofrequency ablation of the small renal mass : a meta
      analysis.
AB  - BACKGROUND: The incidence of renal cell carcinoma is rising because of incidental
      detection of small renal masses (SRMs). Although surgical resection remains the
      standard of care, cryoablation and radiofrequency ablation (RFA) have emerged as
      minimally invasive treatment alternatives. The authors of this report performed a
      comparative meta-analysis evaluating cryoablation and RFA as primary treatment
      for SRMs. METHODS: A search of the MEDLINE database was performed reviewing the
      world literature for clinically localized renal masses treated by cryoablation or
      RFA. RESULTS: Forty-seven studies representing 1375 kidney lesions treated by
      cryoablation or RFA were analyzed. No differences were detected between ablation
      modalities with regard to mean patient age (P = .17), tumor size (P = .12), or
      duration of follow-up (P = .53). Pretreatment biopsy was performed more often for
      cryoablated lesions (82.3%) than for RFA (62.2%; P < .0001). Unknown pathology
      occurred at a significantly higher rate for SRMs that underwent RFA (40.4%)
      versus cryoablation (24.5%; P < .0001). Repeat ablation was performed more often
      after RFA (8.5% vs 1.3%; P < .0001), and the rates of local tumor progression
      were significantly higher for RFA (12.9% vs 5.2%; P < .0001) compared with
      cryoablation. The higher incidence of local tumor progression was found to be
      correlated significantly with treatment by RFA on univariate analysis (P = .001)
      and on multivariate regression analysis (P = .003). Metastasis was reported less
      frequently for cryoablation (1.0%) versus RFA (2.5%; P = .06). Cryoablation
      usually was performed laparoscopically (65%), whereas 94% of lesions that were
      treated with RFA were approached percutaneously. CONCLUSIONS: Ablation of SRMs is
      a viable strategy based on short-term oncologic outcomes. Although extended
      oncologic efficacy remains to be established for ablation modalities, the current
      data suggest that cryoablation results in fewer retreatments and improved local
      tumor control, and it may be associated with a lower risk of metastatic
      progression compared with RFA.

PMID- 18816627
TI  - Fatigue-induced changes in tonic vibration response (TVR) in humans:
      relationships between electromyographic and biochemical events.
AB  - Fatigue-induced changes in the proprioceptive reflex loop were explored in humans
      by using the tonic electromyographic (EMG) response to vibration (TVR) and
      relating it to lactic acidosis (LA) and oxidative stress. TVR was measured in
      flexor digitorum superficialis before and after sustained or intermittent
      handgrip at maximal voluntary contraction (MVC). TVR variations were compared
      with the changes in EMG power spectrum preceding contractile fatigue, the Hoffman
      reflex (H-reflex), and plasma concentrations of LA and thiobarbituric acid
      reactive substances (TBARS). After both sustained and intermittent handgrips, TVR
      amplitude first declined then increased, independently from the changes in EMG
      power spectrum and H-reflex. TVR depression and facilitation were respectively
      concomitant with increases in LA and TBARS. The TVR depression was proportional
      to the increased LA level. The origin of TVR changes after muscle fatigue is
      questioned because the relationship between TVR depression and LA accumulation
      might be temporal, not causal, and changes in muscle stiffness were not explored.

PMID- 18816628
TI  - Defining potency: a comparison of the International Index of Erectile Function
      short version and the Expanded Prostate Cancer Index Composite.
AB  - BACKGROUND: Both the 5-item short version of the International Index of Erectile
      Function (IIEF-5) and the Expanded Prostate Cancer Index Composite (EPIC) have
      been used to assess erectile function. In this study, the authors compared
      various definitions of potency according to the IIEF-5 and the EPIC. METHODS:
      Patients with prostate cancer who had completed the IIEF-5 and the EPIC within 7
      days of each other were included. The Spearman correlation coefficient (rho) was
      calculated to assess the relation between IIEF-5 and EPIC sexual domain scores.
      Concordance of potency rates by IIEF-5 and EPIC was assessed in cross
      tabulations. By calculating the area under the receiver operator characteristics
      (ROC) curve (AUC), the authors ascertained the discriminative ability of the IIEF
      5 score to identify potent men as defined by the EPIC. RESULTS: Analyzing 102
      questionnaire pairs, IIEF-5 and EPIC domain scores were found to be highly
      correlated (rho = 0.776). EPIC sexual domain scores > or =60 had high concordance
      with IIEF-5 scores > or =17 (98%) and with nearly all single-item definitions of
      potency (> or =71%). However, an EPIC sexual domain score > or =80 was a very
      strict definition of potency, and only 54% of patients with IIEF-5 scores > or
      =22 met this threshold. On the basis of ROC analysis (AUC = 0.90), an IIEF-5
      score > or =20 was identified as the ideal cutoff for defining potency and
      corresponded with an EPIC sexual domain score > or =60. CONCLUSIONS: IIEF-5 and
      EPIC scores were highly correlated, but potency rates varied widely, depending on
      the definition of potency. The current results help with the interpretation of
      sexual function outcomes data in patients with prostate cancer.

PMID- 18816629
TI  - Recessive CLCN1 mutation presenting as Thomsen disease.
AB  - This case report describes a young man referred for electrodiagnostic evaluation
      for hand stiffness and intermittent numbness. His needle electromyography
      revealed diffusely increased insertional and spontaneous motor activity in the
      form of myotonic discharges. Given the finding of symptomatic myotonia also in
      his mother, Thomsen myotonia was suspected. Investigations not only confirmed
      Thomsen myotonia, but also led to the identification of a previously reported
      heterozygous Becker mutation in both the proband and his mother.

PMID- 18816630
TI  - The hepatic apelin system: a new therapeutic target for liver disease.
AB  - Apelin is a peptide that plays an important role in heart physiology and
      pathophysiology, inflammation, and angiogenesis. We evaluated whether the
      endogenous apelin system is involved in the pathogenesis of the hepatic
      remodeling and cardiovascular and renal complications occurring in advanced liver
      disease. The circulating levels of apelin, the messenger RNA (mRNA) and protein
      expression of apelin and apelin receptor, the immunohistological detection of
      apelin and apelin receptor, and the effects induced by the chronic administration
      of an apelin receptor antagonist on fibrosis and vessel density were evaluated in
      rats with cirrhosis and ascites and in control rats. The serum levels of apelin
      in patients with cirrhosis were also measured. Apelin levels were higher in rats
      with cirrhosis than in controls. Apelin mRNA showed a four-fold rise only in
      hepatic tissue, but not in the lung, heart, or kidney of rats with cirrhosis.
      These animals also showed hepatic apelin receptor mRNA levels 300 times higher
      than controls. Apelin was highly expressed by stellate cells, whereas apelin
      receptor was overexpressed in the hepatic parenchyma of animals with cirrhosis.
      Rats with cirrhosis treated with the apelin receptor antagonist showed diminished
      hepatic fibrosis and vessel density, improved cardiovascular performance, and
      renal function and lost ascites. Human patients also showed a marked increase in
      apelin levels. CONCLUSION: The selective hepatic activation of the apelin system,
      together with the drop in fibrosis and neoangiogenesis and the improvement in
      cardiovascular and excretory function resulting from apelin receptor blockade,
      points to the hepatic apelin system as a novel therapeutic target in liver
      disease.

PMID- 18816631
TI  - Family history and breast cancer tumour characteristics in screened women.
AB  - Women with a family history of breast cancer have an increased risk of the
      disease. However, since they tend to experience greater surveillance for the
      disease, their breast cancers may be detected at an earlier stage, thus making it
      difficult to assess reliably whether tumour characteristics vary by family
      history. Information on 9,731 Million Women Study participants with screen
      detected breast cancer, diagnosed in 1996-2003, and 37,983 matched controls, who
      also attended routine screening but were not diagnosed with breast cancer, was
      used to estimate adjusted relative risks (RRs) of screen-detected breast cancer
      in women with a family history of the disease. Women with a family history of
      breast cancer had an increased risk of screen-detected breast cancer (RR 1.57;
      95% CI:1.47-1.68) compared with those without such a family history. The RRs were
      1.58 (1.46-1.71) and 1.55 (1.34-1.80) for invasive and in situ breast cancer;
      1.63 (1.49-1.79) and 1.55 (1.32-1.83) for node-negative and node-positive
      disease; and 1.56 (1.42-1.70), 1.75 (1.39-2.21) and 1.71 (1.28-2.29) for ductal,
      lobular and tubular cancers. There was no significant difference in the RR of
      screen-detected breast cancer associated with a family history of the disease
      according to invasiveness, size, nodal status, malignancy grade or morphological
      type of the breast cancer.

PMID- 18816632
TI  - Absence of ESR1 amplification in a series of breast cancers.

PMID- 18816633
TI  - Crohn's disease of the ileal pouch: reality, diagnosis, and management.
AB  - Restorative proctocolectomy with ileal pouch-anal anastomosis has become the
      surgical treatment of choice for patients with ulcerative colitis or
      indeterminate colitis who require surgery. A subset of patients with ileal
      pouches may develop Crohn's disease or a Crohn's disease-like condition of the
      pouch after the surgery. Diagnosis, differential diagnosis, and management can be
      challenging. A combined assessment of endoscopy, histology, radiography, and
      examination under anesthesia is often necessary for an accurate diagnosis. A
      multidisciplinary approach by a medical and surgical team is advocated. It is
      advisable to inform ulcerative colitis patients before the surgery of the
      potential risk for Crohn's disease along with other inflammatory and
      noninflammatory complications.

PMID- 18816634
TI  - Components of cure: treatment of acute lymphoblastic leukemia in Indonesia and
      other low-income countries.

PMID- 18816635
TI  - CT, MRI and ultrasound scanning rates: evaluation of cancer diagnosis, staging
      and surveillance in Ontario.
AB  - OBJECTIVE: To examine practice patterns and rates of computed tomography (CT),
      magnetic resonance imaging (MRI), and abdominal ultrasound (AUS) during staging,
      treatment and surveillance for cancer patients. METHODS: Using Ontario Health
      Insurance Plan billing data linked to the Ontario Cancer Registry, we determined
      rates of CT, MRI, and AUS by body site for breast, colorectal, lung, lymphoma,
      and prostate cancer, from 1998 to 2002. Rates of scans were additionally examined
      by region of patient residence and time from cancer diagnosis. RESULTS: The
      frequency of imaging increased in nearly all scans and tumors over the study
      period. Rates of peri-diagnosis scans varied substantially by region, ranging
      from 1.7-fold variation (CT for lung cancer) to 50-fold variation (MRI for breast
      cancer). For breast cancer, there is possible over-utilization of CT, but overall
      rates of scanning appear reasonable for the other four cancers. CONCLUSIONS:
      Considerable regional variation in imaging rates suggests utilization guidelines
      should be developed or knowledge transfer initiatives are needed to improve
      compliance to existing guidelines. In breast cancer, there appears to be over
      utilization of imaging. Further studies are necessary to determine utilization
      for each stage, the reason scans were obtained, and the impact of scans on
      patient outcomes.

PMID- 18816636
TI  - Vitamin D receptor polymorphisms and the risk of cutaneous melanoma: a systematic
      review and meta-analysis.
AB  - It has been hypothesized that polymorphisms in the vitamin D receptor (VDR) gene
      affect the risk of developing melanoma. However, results often are conflicting,
      and no meta-analysis has been performed to date on published data. Six studies
      (cases, 2152; controls, 2410) that investigated the association between 5 VDR
      polymorphisms (TaqI, FokI, BsmI, EcoRV, and Cdx2) and the risk of melanoma were
      retrieved and analyzed. The model-free approach was applied to meta-analyze these
      molecular association studies. Available data suggested a significant association
      between the BsmI VDR polymorphism and melanoma risk (pooled odds ratio [OR],
      1.30; 95% confidence interval [CI], 1.11-1.53; P= .002; heterogeneity Cochran Q
      test, P> .1), and the population-attributable risk was 9.2%. In contrast, the
      FokI polymorphism did not appear to be associated with such risk (OR, 1.09; 95%
      CI, 0.99-1.21; P= .07; heterogeneity Cochran Q test, P> .1). For the TaqI and the
      EcoRV polymorphisms, significant between-study heterogeneity did not support
      genotype data pooling. Only 1 study investigated the Cdx2 variant, and the
      findings were negative. Current evidence is in favor of an association between 1
      VDR gene polymorphism (BsmI) and the risk of developing melanoma. The current
      findings prompt further investigation on this subject and indirectly support the
      hypothesis that sun exposure may have an antimelanoma effect through activation
      of the vitamin D system.

PMID- 18816637
TI  - Novel biomarkers for risk of prostate cancer: results from a case-control study.
AB  - BACKGROUND: Although the estrogens estrone and estradiol are recognized to play
      very important roles in the risk of developing prostate cancer (Pca), the
      molecular mechanism by which estrogens initiate and/or promote Pca is still
      unknown. Substantial evidence supports that specific metabolites of estrogens,
      catechol estrogen quinones, can react with DNA to form depurinating estrogen-DNA
      adducts. Apurinic sites derived from depurination of these adducts can induce
      mutations leading to cancer. Once released from DNA, depurinating estrogen-DNA
      adducts are shed from cells into the bloodstream and excreted in urine. By
      analyzing profiles of estrogen metabolites, conjugates, and depurinating DNA
      adducts in urine from men with and without prostate cancer, potential biomarkers
      of Pca can be detected. The goal of this case-control study was to detect and
      identify potential biomarkers of Pca. METHODS: Urine samples from fourteen cases,
      men diagnosed with Pca, and 125 controls, men who had not been diagnosed with
      Pca, were partially purified by solid phase extraction and analyzed by
      ultraperformance liquid chromatography/tandem mass spectrometry. The urinary
      levels of androgens, estrogens, estrogen metabolites, conjugates and depurinating
      DNA adducts were measured. RESULTS: The ratio of depurinating estrogen-DNA
      adducts to the sum of the corresponding estrogen metabolites and conjugates was
      significantly higher in cases (median: 57.34) compared to controls (median:
      23.39) (P < 0.001). CONCLUSIONS: This study suggests that depurinating estrogen
      DNA adducts could serve as potential biomarkers to predict risk of Pca. They also
      could be useful tools for early clinical diagnosis and development of suitable
      strategies to prevent Pca.

PMID- 18816641
TI  - Health-care providers' compliance with childhood acute lymphoblastic leukemia
      protocol in Indonesia.
AB  - BACKGROUND: Non-compliance with childhood acute lymphoblastic leukemia (ALL)
      protocol is an important determinant of poor treatment outcome. Non-compliance
      with protocol may not only concern parents or patients, but may also concern
      health-care providers (HCP). Our study examines the accuracy of leukemia risk
      classification and attitude of HCP toward protocol compliance in Indonesia.
      PROCEDURE: A combined retrospective study of medical records (MR) and a cross
      sectional questionnaire study with HCP were conducted. Accurate ALL risk
      classification in MR was assessed. HCP' knowledge of risk classification and
      their attitude toward protocol compliance were examined. RESULTS: A total of 164
      MR patients with ALL were assessed and 97 HCP were interviewed. The protocol
      criteria for high-risk (HR) were not complete in 82 MR (50%). Of 97 HCP, 95% did
      not mention all five protocol criteria for HR. Both in the MR as well as in the
      questionnaires lymphoblast count on day 8 of chemotherapy, as early response to
      treatment, was the most frequently missed item (missing in 35% of MR and 85% of
      questionnaires). Only 14% of respondents actually checked with parents whether
      they administered the prescribed medicines. CONCLUSIONS: Our study shows that HCP
      should improve their knowledge and assessment of childhood ALL risk
      classification, especially lymphoblast count on day 8 of chemotherapy. Proper
      risk classification and subsequent correct treatment may enable more children to
      be cured of leukemia.

PMID- 18816642
TI  - Congenital lipomatous overgrowth, vascular malformations, and epidermal nevi
      (CLOVE) syndrome: CNS malformations and seizures may be a component of this
      disorder.
AB  - A newborn girl was found to have a massive lymphatic truncal vascular
      malformation with overlying cutaneous venous anomaly associated with overgrown
      feet and splayed toes. These manifestations comprise the recently described CLOVE
      syndrome. She also had cranial asymmetry and developed generalized seizures,
      which were treated with anticonvulsants. Cranial CT showed encephalomalacia,
      widening of the ventricles and the sulci, hemimegalencephaly (predominantly white
      matter) and partial agenesis of corpus callosum. Review of the literature
      identified several other patients with CLOVE syndrome, some of whom were
      misdiagnosed as having Proteus syndrome, with strikingly similar manifestations.
      We conclude that CNS manifestations including hemimegalencephaly, dysgenesis of
      the corpus callosum, neuronal migration defects, and the consequent seizures, may
      be an rarely recognized manifestation of CLOVE syndrome.

PMID- 18816645
TI  - Unusual presentation of a severe autosomal recessive anhydrotic ectodermal
      dysplasia with a novel mutation in the EDAR gene.
AB  - We report on an 18-year-old woman, born to first-cousin parents, presenting with
      a severe form of anhydrotic ectodermal dysplasia (EDA/HED). She had sparse hair,
      absent limb hair, absent sweating, episodes of hyperpyrexia, important
      hypodontia, and hyperconvex nails. She also showed unusual clinical
      manifestations such as an absence of breasts, a rudimentary extranumerary areola
      and nipple on the left side, and marked palmo-plantar hyperkeratosis. Light
      microscopy of skin biopsies showed orthokeratotic hyperkeratosis and absence of
      sweat glands. A novel homozygous mutation (IVS9 + 1G > A) in the EDAR gene was
      identified. This mutation results in a total absence of EDAR transcripts and
      consequently of the EDAR protein, which likely results in abolition of all
      ectodysplasin-mediated NF-kappaB signaling. This is the first complete loss-of
      function mutation in the EDAR gene reported to date, which may explain the
      unusual presentation of HED in this patient, enlarging the clinical spectrum
      linked to the dysfunction of the ectodysplasin mediated NF-kappaB signaling.

PMID- 18816644
TI  - Metabotropic glutamate receptor 5 activation inhibits microglial associated
      inflammation and neurotoxicity.
AB  - The Group I metabotropic glutamate receptor 5 (mGluR5) can modulate addiction,
      pain, and neuronal cell death. Expression of some mGluRs, such as Group II and
      III mGluRs, has been reported in microglia and may affect their activation.
      However, the expression and role of mGluR5 in microglia is unclear. Using
      immunocytochemistry and Western blot, we demonstrate that mGluR5 protein is
      expressed in primary microglial cultures. Activation of mGluR5 using the
      selective agonist (RS)-2-chloro-5-hydroxyphenylglycine (CHPG) significantly
      reduces microglial activation in response to lipopolysaccharide, as indicated by
      a reduction in nitric oxide, reactive oxygen species, and TNFalpha production.
      Microglial induced neurotoxicity is also markedly reduced by CHPG treatment. The
      anti-inflammatory effects of CHPG are not observed in microglial cultures from
      mGluR5 knockout mice and are blocked by selective mGluR5 antagonists, suggesting
      that these actions are mediated by the mGluR5 receptor. Anti-inflammatory actions
      of mGluR5 activation are attenuated by phospholipase C and protein kinase C
      inhibitors, as well as by calcium chelators, suggesting that the mGluR5
      activation in microglia involves the G(alphaq)-protein signal transduction
      pathway. These data indicate that microglial mGluR5 may represent a novel target
      for modulating neuroinflammation, an important component of both acute and
      chronic neurodegenerative disorders.

PMID- 18816647
TI  - Do extraintestinal manifestations predict disease course, severity, and/or
      activity in IBD?

PMID- 18816648
TI  - Are antibiotics useful in the treatment of IBD?

PMID- 18816649
TI  - Is there a role for multidrug therapy in active Crohn's disease?

PMID- 18816650
TI  - Why are molecular mechanisms of immune activation important in IBD?

PMID- 18816651
TI  - Nf-kappa B signaling cascade and IBD: turn it down?

PMID- 18816652
TI  - Could stress play a role in IBD?

PMID- 18816653
TI  - How do you avoid and treat steroid side effects?

PMID- 18816654
TI  - Why study animal models of IBD?

PMID- 18816655
TI  - How can IBD be distinguished from IBS?

PMID- 18816656
TI  - Should patients with Crohn's disease be in colonoscopic surveillance programs?

PMID- 18816657
TI  - Poststroke restless legs syndrome and lesion location: anatomical considerations.
AB  - Several case studies have reported on restless legs syndrome (RLS) associated
      with stroke. In this study, we investigated the prevalence and the lesion
      topography of poststroke RLS. There were 137 patients with ischemic stroke
      included in this study. The diagnosis of RLS was made 1 month after the index
      stroke using the criteria established by the International RLS Study Group. All
      patients enrolled underwent magnetic resonance imaging within 7 days of the onset
      of the stroke. The prevalence of stroke-related RLS was calculated, and the
      topography of the associated ischemic lesions was analyzed. Among 137 patients,
      17 patients (12.4%) were diagnosed with RLS after a stroke. Stroke-related RLS
      was found in 10 out of 33 patients with a basal ganglia/corona radiata infarct
      (30.3%), 1 out of 8 patients with an internal capsular infarct (12.5%), and 1 out
      of 7 patients with a thalamic infarct (14.3%). In addition, one out of 54 with a
      cortical lesion with/without subcortical involvement (1.9%), and 4 out of 18
      patients with a pontine lesion (22.2%) had RLS. The analysis of the lesions in
      the cortical and subcortical group showed only 1 patient in the cortical group
      had stroke-related RLS, whereas 16 in the subcortical group had stroke-related
      RLS. The results of this study suggest that lesions of the subcortical brain
      areas such as the pyramidal tract and the basal ganglia-brainstem axis, which are
      involved in motor functions and sleep-wake cycles, may lead to RLS symptoms in
      patients after an ischemic stroke.

PMID- 18816658
TI  - Is there a role for infliximab in the treatment of severe ulcerative colitis?:
      the American experience.

PMID- 18816659
TI  - Management of perianal fistula in Crohn's disease.

PMID- 18816660
TI  - IBD and pregnancy.

PMID- 18816661
TI  - Is genomic analysis relevant to IBD?

PMID- 18816662
TI  - Can loss of immune tolerance cause IBD?

PMID- 18816663
TI  - Is there a threshold for the deleterious effect of smoking in Crohn's disease?

PMID- 18816664
TI  - How often do patients with IBD have symptom recurrence?

PMID- 18816665
TI  - What are the critical histologic features in the diagnosis of ulcerative colitis?

PMID- 18816666
TI  - Do heat shock proteins play any role in gut inflammation?

PMID- 18816667
TI  - What are the minimal requirements for a diagnosis of inflammatory bowel disease?

PMID- 18816668
TI  - Radiologic testing in Crohn's disease.

PMID- 18816669
TI  - Adverse events of IBD therapies.

PMID- 18816670
TI  - What are the guidelines for treating adenoma-like DALMs in UC?

PMID- 18816671
TI  - Medical induction of active Crohn's ileitis: evidence-based management.

PMID- 18816672
TI  - Which type of treatment is advisable in the prevention of recurrence after
      surgery in Crohn's disease?

PMID- 18816673
TI  - How often and for how long are IBD patients expected to be sick, off work, or in
      hospital each year?

PMID- 18816674
TI  - Do antibodies have a role in IBD pathogenesis?

PMID- 18816675
TI  - What is the prognosis of ulcerative colitis?

PMID- 18816676
TI  - What is the role of endoscopy in the postoperative management of Crohn's disease?

PMID- 18816677
TI  - What is the role of endoscopy in predicting Crohn's disease relapse or course?

PMID- 18816678
TI  - What is the role and significance of serum and stool biomarkers in the diagnosis
      of IBD?
AB  - Biomarkers hold promise for identifying high-risk individuals who may go on to
      develop IBD as well as prognosticate disease behavior. Stool markers have not
      been readily accepted but may be more sensitive and specific than our serum
      biomarkers for evaluating disease activity. Ultimately, genomic and proteomic
      approaches will be used to identify novel biomarkers in IBD.

PMID- 18816679
TI  - What is the optimal maintenance treatment for ulcerative colitis?

PMID- 18816680
TI  - Is it always necessary to treat CD patients?

PMID- 18816681
TI  - What is the time for surgery in severe Crohn's disease?

PMID- 18816682
TI  - Is IBD different in the elderly?

PMID- 18816683
TI  - What is the link between the use of tobacco and IBD?

PMID- 18816684
TI  - Why are cytokines targeted for biological therapy in IBD?

PMID- 18816685
TI  - What is the effect of inflammation on intestinal function?

PMID- 18816686
TI  - How long is it advisable to continue maintenance treatment of Crohn's disease?

PMID- 18816687
TI  - Does smoking decrease the response to infliximab in patients with Crohn's
      disease?

PMID- 18816688
TI  - Is diet a factor in the pathogenesis of IBD?

PMID- 18816689
TI  - Breastfeeding and inflammatory bowel disease.

PMID- 18816690
TI  - Does the behavior of Crohn's disease change over time?

PMID- 18816691
TI  - What is the cancer risk in Crohn's disease?

PMID- 18816692
TI  - Management of Wilms tumors in Drash and Frasier syndromes.
AB  - BACKGROUND: Children with WT1 gene-related disorders such as Denys-Drash syndrome
      (DDS) and Frasier syndrome (FS) are at increased risk of Wilms tumor and end
      stage renal disease. We investigated whether Wilms tumors in these patients
      displayed a specific phenotype or behavior and whether nephron-sparing surgery
      was beneficial. PROCEDURE: We retrospectively studied all patients with DDS, FS,
      or other WT1 mutations treated at our institutions between 1980 and 2007.
      RESULTS: We identified 20 patients, of whom 18 had benign or malignant tumors.
      Wilms tumors occurred in 15 patients, being unilateral in 10 and bilateral in 5
      (20 tumors). Median age at Wilms tumor diagnosis was 9 months. No patients had
      metastases. According to the International Society of Pediatric Oncology Working
      Classification, there were 19 intermediate-risk tumors and one high-risk tumor;
      no tumor was anaplastic. In patients with nephropathy who underwent unilateral
      nephrectomy for Wilms tumor or nephron-sparing surgery for bilateral Wilms tumor,
      mean time to dialysis was 11 or 9 months, respectively. Other tumors included
      three gonadoblastomas (in two patients), one retroperitoneal soft-tissue tumor,
      and one transitional cell papilloma of the bladder. Two patients, both with stage
      I Wilms tumor, died from end-stage renal disease-related complications. The
      median follow-up time for the 18 survivors was 136 months (range, 17-224 months).
      CONCLUSION: Most Wilms tumors in children with WT1-related disorders were early
      stage and intermediate-risk tumors, with a young age at diagnosis. In patients
      without end-stage renal disease, nephron-sparing surgery should be considered for
      delaying the onset of renal failure.

PMID- 18816693
TI  - Atypical parkinsonism in the Caribbean island of Guadeloupe: etiological role of
      the mitochondrial complex I inhibitor annonacin.
AB  - On the French West Indian island of Guadeloupe, atypical parkinsonian patients
      represent two-thirds of all cases of parkinsonism, which is exceptionally
      frequent compared to epidemiological data from European countries where atypical
      parkinsonism accounts for only approximately 5% of all cases. The clinical entity
      was a unique combination of levodopa-resistant parkinsonism, tremor, myoclonus,
      hallucinations, REM sleep behavior disorder and fronto-subcortical dementia.
      Based on the presence or the absence of supranuclear gaze palsy, two subgroups of
      patients were distinguished. In patients with oculomotor signs that came to
      autopsy, neuronal loss was found to predominate in the substantia nigra and the
      striatum but other brain areas were also affected, including the frontal cortex.
      In addition, tau-containing lesions were detected throughout the brain.
      Epidemiological data suggested a close association of the disease with the
      regular consumption of soursop, a tropical annonaceous plant. Experimental
      studies performed in midbrain cell cultures identified annonacin, a selective
      mitochondrial complex I inhibitor contained in the fruit and leaves of soursop,
      as a probable etiological factor. Consistent with this view, chronic
      administration of annonacin to rats through Alzet osmotic minipumps showed that
      annonacin was able to reproduce the brain lesions characteristic of the human
      disease.

PMID- 18816694
TI  - Total body bone measurements: a cross-sectional study in children with acute
      lymphoblastic leukemia during and following completion of therapy.
AB  - BACKGROUND: Abnormalities in bone mineral density (BMD) occur in children treated
      for acute lymphoblastic leukemia (ALL). However, BMD estimates have been
      performed using varied instruments, reference data, and interpretations. This
      exploratory cross sectional study to evaluate bone mass in children with ALL,
      uses an algorithm that serially adjusts for variables known to affect pediatric
      bone measures by dual energy X-ray absorptiometry (DXA), based on models
      developed in 1,218 healthy children and adolescents. PROCEDURE: Anthropometry,
      DXA scans, and factors with possible influence on bone mass were evaluated in 21
      ALL patients receiving chemotherapy and 20 in the follow-up phase. Main outcome
      was treatment group differences in Z-scores for total body bone mineral content
      (BMC), bone area (Area), and areal BMD (aBMD). RESULTS: Mean Z-scores for the
      entire study population for BMC, Area, and aBMD were significantly less than
      zero. Among possible contributing factors, only calcium intake was a significant
      co-variate. Comparison between treatment groups showed that least-square mean Z
      scores for patients on-therapy for at least 12 months were significantly lower
      than those off therapy for at least 12 months (P: 0.0008-0.044), except for BMC
      at last step of the algorithm (adjusted for sex, age, ethnicity, height, weight,
      and bone area). CONCLUSIONS: Evaluation of total body DXA by this algorithm is
      consistent with better general bone status in those off-therapy. However, in this
      small exploratory study, the lack of significant difference between Z-scores for
      fully adjusted BMC in on- versus off-therapy groups suggests possible risk of low
      peak bone mass. Additional longitudinal evaluation is warranted.

PMID- 18816695
TI  - Pseudochoreoathetosis can be the first clinical manifestation of anti-Hu
      neuropathy associated with squamous cell carcinoma.

PMID- 18816696
TI  - Optimizing algorithms to identify Parkinson's disease cases within an
      administrative database.
AB  - Patients assigned the diagnostic ICD-9-CM code for Parkinson's disease (PD) in an
      administrative database may not truly carry that diagnosis because of the various
      error sources. Improved ability to identify PD cases within databases may
      facilitate specific research goals. Experienced chart reviewers abstracted the
      working diagnosis of all 577 patients assigned diagnostic code 332.0 (PD) during
      1 year at a VA Healthcare System. We then tested the ability of various
      algorithms making use of PD and non-PD diagnostic codes, specialty of clinics
      visited, and medication prescription data to predict the abstracted working
      diagnosis. Chart review determined 436 (75.6%) patients to be PD or Possibly PD,
      and 141 (24.4%) to be Not PD. Our tiered consensus algorithm preferentially used
      data from specialists over nonspecialists improved PPV to 83.2% (P = 0.003 vs.
      baseline). When presence of a PD prescription was an additional criterion, PPV
      increased further to 88.2% (P = 0.04 vs. without medication criterion), but
      sensitivity decreased from 87.4 to 77.1% (P = 0.0001). We demonstrate that
      algorithms provide better identification of PD cases than using a single
      occurrence of the diagnostic code for PD, and modifications of such algorithms
      can be tuned to maximize parameters that best meet the goals of a particular
      database query.

PMID- 18816697
TI  - Nordic walking improves mobility in Parkinson's disease.
AB  - Nordic walking may improve mobility in Parkinson's disease (PD). Here, we
      examined whether the beneficial effects persist after the training period. We
      included 19 PD patients [14 men; mean age 67.0 years (range 58-76); Hoehn and
      Yahr stage range 1-3] who received a 6-week Nordic walking exercise program.
      Outcome was assessed prior to training (T1), immediately after the training
      period (T2) and-in a subgroup of 9 patients--5 months after training (T3). At T2,
      we observed a significant improvement in timed 10-m walking, the timed get-up-and
      go-test (TUG), the 6-min walking test and quality of life (PDQ-39). All treatment
      effects persisted at T3. Compliance was excellent, and there were no adverse
      effects. These preliminary findings suggest that Nordic walking could provide a
      safe, effective, and enjoyable way to reduce physical inactivity in PD and to
      improve the quality of life. A large randomized clinical trial now appears
      justified.

PMID- 18816698
TI  - A study of rituximab and ifosfamide, carboplatin, and etoposide chemotherapy in
      children with recurrent/refractory B-cell (CD20+) non-Hodgkin lymphoma and mature
      B-cell acute lymphoblastic leukemia: a report from the Children's Oncology Group.
AB  - BACKGROUND: To estimate the response rate and therapy related toxicities of the
      anti-CD20 monoclonal antibody rituximab when combined with chemotherapy including
      ifosfamide, carboplatin, and etoposide (ICE) in patients with relapsed and
      refractory B-cell non-Hodgkin lymphoma and mature B-cell acute lymphoblastic
      leukemia (B-ALL). METHODS: Patients received rituximab and ICE for 1-3 cycles,
      depending upon response. Rituximab (375 mg/m(2)) was given on day 1 and 3 of each
      cycle (day 1 only for cycle 3), with ifosfamide (3,000 mg/m(2)) and etoposide
      (100 mg/m(2)) given on days 3, 4, and 5 and carboplatin (635 mg/m(2)) given on
      day 3 only. RESULTS: Twenty-one patients were enrolled, of whom 20 were eligible
      and evaluable. Although hematologic toxicities were common, only one patient was
      removed from study due to prolonged myelosuppression. Toxicities related to
      infusions of rituximab were frequent but manageable. Of the six eligible patients
      with diffuse large B-cell lymphoma, three achieved complete remission (CR), one
      had stable disease (SD), and two had progressive disease (PD). Of the 14 eligible
      patients with Burkitt lymphoma and B-ALL, there were four complete responses
      (CR), five partial responses (PR), one SD, and four with PD. Thus, the CR/PR rate
      for the entire group was 12/20 (60%). Following completion of protocol therapy
      six patients were able to proceed to consolidation with high-dose therapy and
      stem cell rescue. CONCLUSIONS: The combination of rituximab and ICE chemotherapy
      was associated with an encouraging objective response (OR) rate and an acceptable
      toxicity profile.

PMID- 18816699
TI  - Applying diagnostic criteria for type 1 von Willebrand disease to a pediatric
      population.
AB  - BACKGROUND: Definitive diagnosis of type 1 von Willebrand disease (VWD) remains
      elusive in clinical practice. Both the International Society on Thrombosis and
      Haemostasis (ISTH) and the Hospital for Sick Children (HSC) have proposed
      diagnostic criteria for type 1 VWD, which include abnormal laboratory values,
      significant mucocutaneous bleeding history, and/or positive family history. The
      objective of this study was to apply ISTH and HSC criteria to a large pediatric
      population previously diagnosed with type 1 VWD. We hypothesized that a
      substantial number of patients would not meet these diagnostic criteria.
      PROCEDURE: We performed a retrospective medical record review of all type 1 VWD
      patients at a single children's hospital. Frequencies of fit for ISTH and HSC
      diagnostic criteria were calculated. RESULTS: Of 201 patients, 4.5% and 34% met
      the ISTH and HSC definitions, respectively. An additional 15% (ISTH) and 56%
      (HSC) met the definition of possible disease. For each definition, criteria for
      significant bleeding were most likely to be met, while criteria for abnormal
      laboratory values were least likely. When defined as simply VWF:Ag 5-20 IU/ml, as
      recently proposed by the ISTH, only 9% of patients met the definition of type 1
      VWD. CONCLUSIONS: ISTH criteria failed to identify the majority of children and
      adolescents who presented to medical attention with significant mucocutaneous
      bleeding. Further work is needed to develop diagnostic criteria with improved
      clinical validity in the pediatric setting.

PMID- 18816700
TI  - Hemophagocytic lymphohistiocytosis in very young infants.
AB  - We report three cases of hemophagocytic lymphohistiocytosis (HLH) in infants
      within the first 6 weeks of life. Diagnosis of HLH was made early after symptoms
      started. All three cases were successfully treated with dexamethasone and none
      relapsed, indicating that not all cases of HLH in very young infants are
      familial.

PMID- 18816701
TI  - Inflammatory bowel disease: does disease location at presentation predict disease
      course?

PMID- 18816702
TI  - What are innate and acquired immunity, and why are they important in IBD?

PMID- 18816703
TI  - Are clinical outcomes in IBD improved by multidisciplinary clinics?

PMID- 18816704
TI  - Should family members of IBD patients be screened for CARD15/NOD2 mutations?

PMID- 18816705
TI  - How long is it advisable to prolong maintenance treatment of patients with
      ulcerative colitis?

PMID- 18816706
TI  - What can we expect from endoscopic dilation of the stenotic tract in Crohn's
      disease?

PMID- 18816707
TI  - Is IBD associated with a stressful lifestyle?

PMID- 18816708
TI  - What is the risk that a child will develop inflammatory bowel disease if 1 or
      both parents have IBD?

PMID- 18816709
TI  - Is there a role for defensins in IBD?

PMID- 18816710
TI  - What is the role of growth factors in IBD?

PMID- 18816711
TI  - Are physicians biased in their choices of therapy to recommend to patients with
      IBD?

PMID- 18816712
TI  - In the case of nonresponse, what is the second-level treatment for induction of
      remission in Crohn's disease?

PMID- 18816713
TI  - How do you judge relapse in Crohn's disease?

PMID- 18816714
TI  - What new endoscopic imaging modalities will become important in the diagnosis of
      IBD?

PMID- 18816715
TI  - How often is IBD diagnosed incidentally at screening colonoscopy done for
      colorectal cancer surveillance or other reasons?

PMID- 18816716
TI  - Are there epidemiological differences between Crohn's disease and ulcerative
      colitis?

PMID- 18816717
TI  - Is IBD caused by a Helicobacter pylori infection?

PMID- 18816718
TI  - What is the role of apoptosis in the normal and inflamed intestine?

PMID- 18816719
TI  - What is the role of cytokines and chemokines in IBD?

PMID- 18816720
TI  - How have animal models of IBD contributed to advance IBD therapy?

PMID- 18816721
TI  - Future of IBD pathogenesis: how much work is left to do?

PMID- 18816722
TI  - Flare factor: are there any triggering factors associated with onset of clinical
      symptoms or disease relapse?

PMID- 18816723
TI  - Are there any ethnic groups that are more likely to develop IBD?

PMID- 18816724
TI  - Does the mucosal microcirculation play a role in IBD?

PMID- 18816725
TI  - What histologic features best differentiate Crohn's disease from ulcerative
      colitis?

PMID- 18816726
TI  - Is colorectal cancer surveillance cost-effective in patients with ulcerative
      colitis?

PMID- 18816727
TI  - What are the rules when treatment with 6-MP/AZA is started?

PMID- 18816728
TI  - Is IBD an autoimmune disorder?

PMID- 18816729
TI  - Does inflammatory bowel disease develop in infants?

PMID- 18816730
TI  - Does the incidence of IBD increase when persons move from a low- to a high-risk
      area?

PMID- 18816731
TI  - Does the phenotype of Crohn's disease in an individual remain stable over time?

PMID- 18816732
TI  - Is Mycobacterium paratuberculosis or any other infectious agent involved in the
      pathogenesis of IBD?

PMID- 18816733
TI  - What are toll-like receptors and what role may they have in IBD?

PMID- 18816734
TI  - Is the Th1/Th2 paradigm of immune regulation applicable to IBD?

PMID- 18816735
TI  - Is there a gender difference in the prevalence of Crohn's disease or ulcerative
      colitis?

PMID- 18816736
TI  - What is the importance of appendectomy in the natural history of IBD?

PMID- 18816737
TI  - What is the function of cyclooxygenases in the normal and inflamed intestine?

PMID- 18816738
TI  - What are the mechanisms of fibrosis in IBD?

PMID- 18816739
TI  - Do metalloproteinases contribute to tissue destruction or remodeling in the
      inflamed gut?

PMID- 18816740
TI  - How useful is the Vienna Classification in clinical practice?

PMID- 18816741
TI  - What kind of advice regarding way of life should be given to patients with IBD?

PMID- 18816742
TI  - How to judge the response to treatment in ulcerative colitis?

PMID- 18816743
TI  - Adhesion molecule therapeutics in IBD.

PMID- 18816744
TI  - What is the optimal maintenance treatment for Crohn's disease?

PMID- 18816745
TI  - What is the peak age for onset of IBD?

PMID- 18816746
TI  - What is the role of patient education in the care of IBD?

PMID- 18816747
TI  - What is the optimal interval of surveillance colonoscopy in patients with long
      standing ulcerative colitis?

PMID- 18816748
TI  - Which therapies are advisable in pouchitis?

PMID- 18816749
TI  - What do the terms "genetic predisposition" and "genetic heterogeneity" mean in
      relation to inflammatory bowel disease?

PMID- 18816750
TI  - Are patients with IBD knowledgeable about the risks of their medications?

PMID- 18816751
TI  - Do different animal models of IBD serve different purposes?

PMID- 18816752
TI  - What's the best way to differentiate infectious colitis (acute self-limited
      colitis) from IBD?

PMID- 18816753
TI  - What are the differences in treatment of ulcerative colitis between pediatric and
      adult patients?

PMID- 18816754
TI  - In the case of nonresponse to steroids, what is the second level of treatment in
      ulcerative colitis?

PMID- 18816755
TI  - Crohn's surgery: are there differences between the types of anastomosis?

PMID- 18816756
TI  - Inflammatory bowel disease: the difference between children and adults.

PMID- 18816757
TI  - Does IBD run in families?

PMID- 18816758
TI  - Do HLA antigens predict the occurrence of extraintestinal manifestations of IBD?

PMID- 18816759
TI  - Does the phenotype at diagnosis (e.g., fibrostenosing, inflammatory, perforating)
      predict the course of Crohn's disease?

PMID- 18816760
TI  - Is it always therapeutically important to distinguish between Crohn's disease and
      ulcerative colitis?

PMID- 18816761
TI  - What is the optimal maintenance treatment for perianal Crohn's disease?

PMID- 18816762
TI  - How often do IBD patients require resection of their intestine?

PMID- 18816763
TI  - Are there different types of Crohn's disease?

PMID- 18816764
TI  - Do non-immune cells have a role in IBD?

PMID- 18816765
TI  - What is the incidence, prevalence, and natural history of indeterminate colitis?

PMID- 18816766
TI  - Do changes in intestinal permeability predict disease relapse in Crohn's disease?

PMID- 18816767
TI  - Which are the 5-ASA compound side effects and how is it possible to avoid them?

PMID- 18816768
TI  - Use of combination therapy in IBD.

PMID- 18816769
TI  - What is the optimal therapy for severe ulcerative colitis?

PMID- 18816770
TI  - What are the guidelines for using biologics in pediatric patients?

PMID- 18816771
TI  - How do genetics help an understanding of IBD epidemiology?

PMID- 18816772
TI  - What is "physiological" intestinal inflammation and how does it differ from
      "pathological" inflammation?

PMID- 18816773
TI  - What is the role of the enteric commensal flora in IBD?

PMID- 18816774
TI  - How often is a diagnosis of ulcerative colitis changed to Crohn's disease and
      vice versa?

PMID- 18816775
TI  - Are there differences in type, dosage, and method of administration for the
      systemic steroids in IBD treatment?

PMID- 18816776
TI  - Why are genetic studies important in IBD?

PMID- 18816777
TI  - What role does intestinal permeability have in IBD pathogenesis?

PMID- 18816778
TI  - Is virtual colonography useful in the diagnosis or management of inflammatory
      bowel diseases?

PMID- 18816779
TI  - How prevalent are extraintestinal manifestations at the initial diagnosis of IBD?

PMID- 18816780
TI  - Is there a role for infliximab in severe ulcerative colitis?: the European
      experience.

PMID- 18816781
TI  - When is it time for surgery in severe ulcerative colitis?

PMID- 18816782
TI  - I am Jewish: what is my risk of developing Crohn's disease?

PMID- 18816783
TI  - What is the prognosis of Crohn's disease?

PMID- 18816784
TI  - How does IBD affect quality of life?

PMID- 18816785
TI  - Is narcotic addiction more prevalent in IBD patients?

PMID- 18816786
TI  - Does rectal sparing ever occur in ulcerative colitis?

PMID- 18816787
TI  - What is the role of serological markers in the diagnosis of IBD?
AB  - Research and technological advancements have fostered a novel approach to
      understanding the intricate relationship between genetic and clinical expression
      of disease. Both genetic and serum antibody markers hold the most promise in
      helping researchers better comprehend disease heterogeneity and natural history.
      Although our current gold standard diagnostic tests do not possess this
      capability, exciting preliminary research suggests IBD-specific antibody markers
      may serve as predictors of an individual's disease course. Thus, the foundation
      has been laid upon which the discovery of novel IBD-specific and IBD-sensitive
      markers will enable researchers to identify at-risk individuals, as well as
      diagnose IBD and stratify patients into homogeneous subtypes with certainty.
      Clinicians can then create and implement individual treatment plans designed to
      improve the long-term prognosis of these chronic diseases.

PMID- 18816788
TI  - Differential alteration of hippocampal excitatory synaptic transmission by
      cannabinoid ligands.
AB  - Cannabinoid compounds affect synaptic activity and plasticity in numerous brain
      areas by activating CB1 receptors (CB1). In hippocampus, varying results have
      been obtained on the extent and site of cannabinoid actions on excitatory
      transmission, ranging from no effect to complete obliteration of synaptic
      responses. Here we used the rat hippocampal slice preparation to study and
      compare the effect of various synthetic and endogenous CB1 ligands on excitatory
      synaptic transmission. The full CB1 agonist WIN55212-2 (WIN2) greatly decreased
      excitatory synaptic transmission by 62%. The effect of WIN-2 was concentration
      dependent (EC50 of 200 nM) and completely prevented by CB1 antagonists. The
      nondegradable partial CB1 agonist R1-methanandamide (mAEA) decreased transmission
      by 25% and the endocannabinoids 2-arachidonylglycerol (2-AG) and anandamide (AEA)
      had no significant effect. The action of AEA was improved by inhibiting its
      degradation but not its transport. The effect of 2-AG was enhanced upon
      inhibition of COX-2 but remained unchanged with blockade of monoacylglycerol
      lipase (MAGL). The observed effects were prevented by CB1 antagonists regardless
      of the ligand used, and paired-pulse paradigms pointed to presynaptic mechanisms
      of cannabinoid action. Our results show that cannabinoid effects on neuronal
      activity differ widely according to the CB1 ligand used. We observed large
      differences between full (synthetic) and partial (endogenous) CB1 agonists in
      altering synaptic transmission, notably because of the involvement of active
      degradation mechanisms.

PMID- 18816789
TI  - Light- and dark-dependent orexinergic neuronal signals promote neurodegenerative
      phenomena accounting for distinct behavioral responses in the teleost Thalassoma
      pavo.
AB  - The neuropeptides hypocretins/orexins (ORX) are known to control state-dependent
      activities such as sleep-wakefulness, energy homeostasis, thermoregulation, and
      maternal behaviors. To date, interests regarding environmental-related ORX-ergic
      neuronal functions have dealt with mammals; only recently is attention beginning
      to be directed toward aquatic vertebrates. Here, photoperiod-dependent effects of
      ORX-A on behavioral, neurodegenerative and transcriptional activities were
      evaluated in some forebrain areas of a teleost Labridae (ornate wrasse,
      Thalassoma pavo). The ornate wrasse, when treated intraperitoneally with a high
      physiological dose (100 ng/g) of ORX-A and exposed to a natural photoperiod
      (12L:12D), exhibited very high (P < 0.001) locomotion and feeding behaviors. ORX
      A in the presence of a constant light photoperiod accounted for numerically even
      greater (>500%) feeding frequencies. Conversely, constant dark conditions very
      strongly reduced feeding habits and moderately (P < 0.05) increased resting
      states. In this case, the same ORX-A and photoperiodic conditions responsible for
      altered behaviors also induced neurodegenerative processes in the different
      hypothalamic, mesencephalic, and telencephalic neuronal fields. Interestingly,
      this ORX-A treatment seemed to be correlated to greater up-regulatory patterns of
      ORX receptor mRNA in these same brain areas, above all under constant light
      conditions rather than natural photoperiod. On the other hand, telencephalic
      sites provided a very active expression capacity during the dark phase. Overall,
      these results suggest for the first time that at least in the ornate wrasse,
      light- and dark-dependent ORX-ergic neuronal activities are able to cause short-
      and long-term abnormal motor behaviors, likely through neurodegenerative and
      transcriptional events in a brain regional manner.

PMID- 18816790
TI  - Interaction between protein kinase C and protein kinase A can modulate
      transmitter release at the rat neuromuscular synapse.
AB  - We used intracellular recording to investigate the functional interaction between
      protein kinase C (PKC) and protein kinase A (PKA) signal transduction cascades in
      the control of transmitter release in the neuromuscular synapses from adult rats.
      Our results indicate that: 1) PKA and PKC are independently involved in
      asynchronous release. 2) Evoked acetylcholine (ACh) release is enhanced with the
      PKA agonist Sp-8-BrcAMP and the PKC agonist phorbol ester (PMA). 3) PKA has a
      constitutive role in promoting a component of normal evoked transmitter release
      because, when the kinase is inhibited with H-89, the release diminishes. However,
      the PKC inhibitor calphostin C (CaC) does not affect ACh release. 4) PKA
      regulates neurotransmission without PKC involvement because, after PMA or CaC
      modulation of the PKC activity, coupling to the ACh release of PKA can normally
      be stimulated with Sp-8-BrcAMP or inhibited with H-89. 5) After PKA inhibition
      with H-89, PKC stimulation with PMA (or inhibition with CaC) does not lead to any
      change in evoked ACh release. However, in PKA-stimulated preparations with Sp-8
      BrcAMP, PKC becomes tonically active, thus potentiating a component of release
      that can now be blocked with CaC. In normal conditions, therefore, PKA was able
      to modulate ACh release independently of PKC activity, whereas PKA stimulation
      caused the PKC coupling to evoked release. In contrast, PKA inhibition prevent
      PKC stimulation (with the phorbol ester) and coupling to ACh output. There was
      therefore some dependence of PKC on PKA activity in the fine control of the
      neuromuscular synaptic functionalism and ACh release.

PMID- 18816791
TI  - Recruitment of pericytes and astrocytes is closely related to the formation of
      tight junction in developing retinal vessels.
AB  - During retinal development, retinal vascularization begins in the inner retinal
      layer and sprouts radially from the optic nerve to reach the periphery of the
      retina. Subsequently, retinal vessels sprout into the deep retinal layer to form
      three parallel of the nerve fiber layer and two plexiform layers. In this
      process, endothelial cells are closely related to astrocytes and pericytes with
      strict chronological order. Here, we provide that the recruitment of pericytes
      and astrocytes to vascular tube of endothelial cells is closely associated with
      the formation of tight junction in developing retinal vessels. At P4, endothelial
      cells of retinal vessels behind the invading front directly contact to pericytes,
      but not to foot processes of astrocytes, where ZO-1 was already weakly
      immunoreactive along retinal endothelial cells. With the progression of retinal
      development, foot processes of astrocytes are gathered around retinal vessels and
      the maturation of tight junction in endothelial cells is clearly defined, which
      was temporally and spatially accordant to the expression of a tight junction
      protein, ZO-1. In addition, tight junction could be formed with contact of
      pericytes to endothelial cells without the prominent ensheathment of astrocytic
      foot processes, which coincided with the appearance of a tight junction protein,
      ZO-1. Therefore, these data demonstrate that the tight junction of endothelial
      cells in the blood-retina barrier could be developed by cellular interactions
      between pericytes, astrocytes, and endothelial cells. Moreover, ZO-1 as well as
      occludin or claudin might demonstrate the tightness of blood-retina barrier in
      developing retina.

PMID- 18816792
TI  - Guanosine improves motor behavior, reduces apoptosis, and stimulates neurogenesis
      in rats with parkinsonism.
AB  - Parkinson's disease (PD) is characterized by progressive degeneration of
      dopaminergic neurons in the substantia nigra pars compacta (SNc) caused by an
      abnormal rate of apoptosis. Endogenous stem cells in the adult mammalian brain
      indicate an innate potential for regeneration and possible resource for
      neuroregeneration in PD. We previously showed that guanosine prevents apoptosis
      even when administered 48 hr after the toxin 1-methyl-4-phenylpyridinium
      (MPP(+)). Here, we induced parkinsonism in rats with a proteasome inhibitor.
      Guanosine treatment reduced apoptosis, increased tyrosine hydroxylase-positive
      dopaminergic neurons and expression of tyrosine hydroxylase in the SNc, increased
      cellular proliferation in the SNc and subventricular zone, and ameliorated
      symptoms. Proliferating cells in the subventricular zone were nestin-positive
      adult neural progenitor/stem cells. Fibroblast growth factor-2-expressing cells
      were also increased by guanosine. Thus, guanosine protected cells from apoptosis
      and stimulated "intrinsic" adult progenitor/stem cells to become dopaminergic
      neurons in rats with proteasome inhibitor-induced PD. The cellular/molecular
      mechanisms underlying these effects may open new avenues for development of novel
      therapeutics for PD.

PMID- 18816793
TI  - Protection against kainate neurotoxicity by ginsenosides: attenuation of
      convulsive behavior, mitochondrial dysfunction, and oxidative stress.
AB  - We previously demonstrated that kainic acid (KA)-mediated mitochondrial oxidative
      stress contributed to hippocampal degeneration and that ginsenosides attenuated
      KA-induced neurotoxicity and neuronal degeneration. Here, we examined whether
      ginsenosides affected KA-induced mitochondrial dysfunction and oxidative stress
      in the rat hippocampus. Treatment with ginsenosides attenuated KA-induced
      convulsive behavior dose-dependently. KA treatment increased lipid peroxidation
      and protein oxidation and decreased the reduced glutathione/oxidized glutathione
      (GSH/GSSG) ratio to a greater degree in the mitochondrial fraction than in the
      hippocampal homogenate. KA treatment resulted in decreased Mn-superoxide
      dismutase expression and diminished the mitochondrial membrane potential.
      Furthermore, KA treatment increased intramitochondrial Ca(2+) and promoted
      ultrastructural degeneration in hippocampal mitochondria. Treatment with
      ginsenosides dose-dependently attenuated convulsive behavior and the KA-induced
      mitochondrial effects. Protection appeared to be more evident in mitochondria
      than in tissue homogenates. Collectively, the results suggest that ginsenosides
      prevent KA-induced neurotoxicity by attenuating mitochondrial oxidative stress
      and mitochondrial dysfunction.

PMID- 18816794
TI  - Seizures increase importin-beta1 expression in NG2+ cells in the rat hippocampus.
AB  - Importins, also called karyopherins, belong to a large family of proteins
      involved in cytoplasm-to-nucleus transport. Transport machinery generally
      involves a complex formed by two different importin subtypes (alpha and beta).
      Both alpha and beta importins are expressed in the brain, and their expression
      and localization is regulated by physiological neuronal activity. Little is known
      about regulation of importin expression in brain pathological conditions. Here we
      studied the expression of importin beta1 (imp beta 1) in the rat hippocampus
      after acute and chronic seizures induced by the glutamate agonist kainic acid
      (KA). The overall content of imp beta 1 mRNA and protein did not change after
      acute KA seizures. However, acute KA seizures rapidly induced the translocation
      of imp beta 1 protein from the cytoplasm to the nucleus in pyramidal CA1 neurons.
      KA-induced imp beta 1 translocation was prevented by the NMDA (N-methyl-D
      aspartic acid) receptor blocker MK-801. After chronic seizures, the overall
      levels of imp beta 1 mRNA and protein did not change in the whole hippocampus.
      Immunohistochemistry revealed a massive loss of imp beta 1-positive neurons in
      pyramidal layers (that degenerated after KA), whereas an increased number of imp
      beta 1-positive cells was detected in the stratum radiatum of rats with chronic
      seizures compared with control animals. Double-labeling experiments identified
      these cells as glial cells expressing the chondroitin sulfate proteoglycan NG2
      (neuron/glial antigen 2), a glial subtype recently shown to regulate hippocampal
      neuron excitability. These data show a differential regulation of imp beta 1
      expression after acute and chronic seizure activity in the rat hippocampus.

PMID- 18816795
TI  - 1,25-Dihydroxyvitamin D3 administration to 6-hydroxydopamine-lesioned rats
      increases glial cell line-derived neurotrophic factor and partially restores
      tyrosine hydroxylase expression in substantia nigra and striatum.
AB  - It has previously been demonstrated that 1,25-dihydroxyvitamin D(3)
      [1,25(OH)(2)D(3)] administration, whether in cell cultures or in vivo to rats,
      increases glial cell line-derived neurotrophic factor (GDNF) expression levels,
      suggesting that this hormone may have beneficial effects in neurodegenerative
      disorders. This study was carried out to explore the effects of 1,25(OH)(2)D(3)
      administration in a 6-OHDA-lesioned rat model of Parkinson's disease on GDNF and
      tyrosine hydroxylase (TH) expression in substantia nigra (SN) and striatum. Two
      groups of animals received 1,25(OH)(2)D(3) intraperitoneally, the first group 7
      days before the unilateral injection of 6-OHDA into the medial forebrain bundle
      (MFB) and the second group 21 days (days 21-28) after the unilateral injection of
      6-OHDA. Animals of both groups were sacrificed on day 28. In addition, two other
      groups received a unilateral injection of either saline or 6-OHDA into the MFB.
      Rats were killed, and the SN and striatum were then removed for GDNF and TH
      determination. Striatal GDNF protein expression was increased on the ipsilateral
      with respect to the contralateral side after 6-OHDA injection alone as well as in
      1,25(OH)(2)D(3)-treated rats before or after 6-OHDA administration. As expected,
      6-OHDA injection induced an ipsilateral decrease in TH-immunopositive neuronal
      cell bodies and axonal terminals in the SN and striatum. However, treatment with
      1,25(OH)(2)D(3) before and after 6-OHDA injection partially restored TH
      expression in SN. These data suggest that 1,25(OH)(2)D(3) may help to prevent
      dopaminergic neuron damage.

PMID- 18816796
TI  - M4 muscarinic receptors are involved in modulation of neurotransmission at
      synapses of Schaffer collaterals on CA1 hippocampal neurons in rats.
AB  - All five subtypes of muscarinic acetylcholine receptors (mAChR; M(1)-M(5)) are
      expressed in the hippocampus, where they are involved both in cognitive functions
      and in synaptic plasticity, such as long-term potentiation (LTP). Muscarinic
      toxins (MTs) are small proteins from mamba snake venoms that display exquisite
      discrimination between mAChRs. MT1 acts as an agonist at M(1) and an antagonist
      at M(4) receptors, with similar affinities for both. MT3, the most selective
      antagonist available for M(4) receptors, infused into the CA1 region immediately
      after training caused amnesia in the rat, indicating the participation of M(4)
      receptors in memory consolidation. Our goal was to investigate the participation
      of M(4) receptor in neurotransmission at the hippocampal Schaffer collaterals-CA1
      synapses. Two different preparations were used: 1) field potential recordings in
      freshly prepared rat hippocampal slices with high-frequency stimulation to induce
      potentiation and 2) whole-cell voltage clamp in cultured hippocampal organotypic
      slices with paired stimuli. In preparation 1, a dose of MT3 that was previously
      shown to cause amnesia blocked LTP; the nonselective antagonist scopolamine
      blocked LTP without affecting basal transmission, although it was depressed with
      higher concentration. In preparation 2, basal transmission was decreased and LTP
      induction was prevented by an MT3 concentration that would bind mainly to M(4)
      receptors. Although M(1) receptors appeared to modulate transmission positively
      at these excitatory synapses, M(1) activation concomitant with M(4) blockade (by
      MT1) only allowed a brief, short-term potentiation. Accordingly, M(4) blockade by
      MT3 strongly supports a permissive role of M(4) receptors and suggests their
      necessary participation in synaptic plasticity at these synapses.

PMID- 18816797
TI  - Developmental regulation of metabotropic glutamate receptor 1 splice variants in
      olfactory bulb mitral cells.
AB  - Alternative splicing of the metabotropic glutamate receptor 1 (mGluR1) receptor
      gene generates two major receptor isoforms, mGluR1a and mGluR1b, differing in
      intracellular function and distribution. However, little is known on the
      expression profiles of these variants during development. We examined the mRNA
      expression profile of mGluR1a/b in microdissected layers and acutely isolated
      mitral cells in the developing mouse olfactory bulb. This analysis showed that
      the two mGluR1 variants are differentially regulated within each bulb layer.
      During the first postnatal week, the mGluR1a isoform replaces GluR1b in the
      microdissected mitral cell layer (MCL) and in isolated identified mitral cells,
      coinciding with a developmental epoch of mitral cell dendritic reorganization.
      Although mGluR1a mRNA is expressed at high levels in both the adult external
      plexiform layer (EPL) and MCL, Western blotting analysis reveals a marked
      reduction of the mGluR1a protein in the MCL, where mitral cell bodies are
      located, and strong labeling in the EPL, which contains mitral cell dendrites.
      This suggests that there is increased dendritic trafficking efficiency of the
      receptor in adult. The temporal and spatial shift in mGluR1b/a expression
      suggests distinct roles of the mGluR1 isoforms, with mGluR1b potentially involved
      in the early mitral cell maturation and mGluR1a in dendritic and synapse
      function.

PMID- 18816798
TI  - Genetic fate mapping of Olig2 progenitors in the injured adult cerebral cortex
      reveals preferential differentiation into astrocytes.
AB  - Olig2 is a basic helix-loop-helix (bHLH) transcription factor essential for
      development of motoneurons and oligodendrocytes. It is known that Olig2(+) cells
      persist in the central nervous system (CNS) from embryonic to adult stages and
      that the number of Olig2(+) progenitors increases in the injured adult CNS.
      Recent studies have demonstrated an inhibitory action of Olig2 on neurogenesis in
      adult CNS, but the fate of Olig2(+) cells in the injured state remains largely
      unknown. To trace directly the fate of Olig2 cells in the adult cerebral cortex
      after injury, we employed the CreER/loxP system to target the olig2 locus. In
      this genetic tracing study, green fluorescent protein (GFP) reporter-positive
      cells labeled after cryoinjury coexpressed glial fibrillary acidic protein
      (GFAP), an astrocytic marker. Electron microscopy also showed that GFP(+) cells
      have the ultrastructural characteristics of astrocytes. Furthermore, GFP(+) cells
      labeled before injury, most of which had been NG2 cells, also produced bushy
      astrocytes. Here we show direct evidence that Olig2(+) cells preferentially
      differentiate into astrocytes, which strongly express GFAP, in response to injury
      in the adult cerebral cortex. These results suggest that reactive astrocytes,
      known to be the main contributors to glial scars, originate, at least in part,
      from Olig2(+) cells.

PMID- 18816799
TI  - Improving NMR protein structure quality by Rosetta refinement: a molecular
      replacement study.
AB  - The structure of human protein HSPC034 has been determined by both solution
      nuclear magnetic resonance (NMR) spectroscopy and X-ray crystallography.
      Refinement of the NMR structure ensemble, using a Rosetta protocol in the absence
      of NMR restraints, resulted in significant improvements not only in structure
      quality, but also in molecular replacement (MR) performance with the raw X-ray
      diffraction data using MOLREP and Phaser. This method has recently been shown to
      be generally applicable with improved MR performance demonstrated for eight NMR
      structures refined using Rosetta (Qian et al., Nature 2007;450:259-264).
      Additionally, NMR structures of HSPC034 calculated by standard methods that
      include NMR restraints have improvements in the RMSD to the crystal structure and
      MR performance in the order DYANA, CYANA, XPLOR-NIH, and CNS with explicit water
      refinement (CNSw). Further Rosetta refinement of the CNSw structures, perhaps due
      to more thorough conformational sampling and/or a superior force field, was
      capable of finding alternative low energy protein conformations that were equally
      consistent with the NMR data according to the Recall, Precision, and F-measure
      (RPF) scores. On further examination, the additional MR-performance shortfall for
      NMR refined structures as compared with the X-ray structure were attributed, in
      part, to crystal-packing effects, real structural differences, and inferior
      hydrogen bonding in the NMR structures. A good correlation between a decrease in
      the number of buried unsatisfied hydrogen-bond donors and improved MR performance
      demonstrates the importance of hydrogen-bond terms in the force field for
      improving NMR structures. The superior hydrogen-bond network in Rosetta-refined
      structures demonstrates that correct identification of hydrogen bonds should be a
      critical goal of NMR structure refinement. Inclusion of nonbivalent hydrogen
      bonds identified from Rosetta structures as additional restraints in the
      structure calculation results in NMR structures with improved MR performance.

PMID- 18816800
TI  - Walking speed during single and dual tasks in Parkinson's disease: which
      characteristics are important?
AB  - The impact of dual tasks on gait in Parkinson's disease (PD) reveals lack of
      automaticity and increased cognitive demands. We explored which characteristics
      explained walking speed with and without dual task interference and if they
      reflected the cognitive demands of the task. In 130 people with PD, gait
      performance was quantified in the home using accelerometers allowing estimates of
      single and dual task walking speed and interference (difference between dual and
      single task). Multiple regression analysis was used to explore the effect of 12
      characteristics representing four domains (personal, motor symptoms, cognitive,
      affective) on gait outcomes. Thirty-seven percent of variance in single task
      speed was explained by increased fear of falling, sex, age, disease severity, and
      depression; 34% of variance in dual task speed was explained by increased fear of
      falling, disease severity, medication, and depression; 12% of variance in
      interference scores was explained by greater disease severity and impaired
      executive function. Personal, motor, affective, and cognitive characteristics
      contribute to walking speed and interference, highlighting the multifactorial
      nature of gait. Different patterns of characteristics for each outcome indicates
      the impact of cognitive demand and task complexity, providing cautious support
      for dual task speed and interference as valid proxy measures of cognitive demand
      in PD gait.

PMID- 18816801
TI  - Motor re-training does not need to be task specific to improve writer's cramp.
AB  - Previous studies showed a beneficial effect of motor re-training in task-specific
      hand dystonia. Here we examined whether re-training needs to specifically focus
      on the task affected by dystonia. 21 patients with writer's cramp were randomly
      assigned to two types of re-training: One group of patients trained drawing and
      writing movements using a pen attached to the bottom of a finger splint. The
      second group used therapeutic putty to train finger movements without exercises
      of drawing and writing movements. Training lasted for 8 weeks. Before re
      training, affected hand and forearm were immobilized for 4 weeks to facilitate
      the responsiveness to re-training. Dystonia was assessed during handwriting using
      the Writer's Cramp Rating Scale. Although no clinical improvement was observed
      immediately after immobilization, 8 weeks of re-training improved task-specific
      dystonia relative to baseline (P = 0.005). Both training modalities were equally
      effective. More severely affected patients benefited most. There was no
      correlation between disease duration and the individual treatment response. Re
      training also improved hand function as indexed by the Arm Dystonia Disability
      Scale (P = 0.008). Kinematic handwriting analysis showed that re-training lowered
      vertical force level and enhanced the fluency of handwriting. We conclude that re
      training does not need to specifically focus on the task affected by dystonia to
      be clinically effective.

PMID- 18816802
TI  - Huntington's disease-like 2 in Brazil--report of 4 patients.
AB  - Huntington's disease-like 2 (HDL2) is a neurodegenerative disorder found in
      people of African ancestry with clinical, radiological, and neuropathological
      manifestations similar to Huntington's disease (HD). HDL2 is caused by a
      pathological expansion of CAG/CTG triplets in exon 2A of the JPH3 gene. We
      describe four cases of HDL2 from four unrelated families, and discuss their
      clinical findings. HDL2 should be considered in every patient with an HD-like
      phenotype who tests negative for the HD mutation, even if African ancestry is not
      immediately apparent.

PMID- 18816803
TI  - Apparent diffusion coefficient of the superior cerebellar peduncle differentiates
      progressive supranuclear palsy from Parkinson's disease.
AB  - The early diagnosis of progressive supranuclear palsy (PSP) may be challenging,
      because of clinical overlapping features with Parkinson's disease (PD) and other
      parkinsonian syndromes such as the Parkinsonian variant of multiple system
      atrophy (MSA-P). Conventional MRI can help in differentiating parkinsonian
      disorders but its diagnostic accuracy is still unsatisfactory. On the basis of
      the pathological demonstration of superior cerebellar peduncle (SCP) atrophy in
      patients with PSP, we assessed the SCP apparent diffusion coefficient (ADC)
      values in patients with PSP, PD, and MSA-P in order to evaluate its differential
      diagnostic value in vivo. Twenty-eight patients with PSP (14 with possible-PSP
      and 14 with probable-PSP), 15 PD, 15 MSA-P, and 16 healthy subjects were studied
      by using diffusion weighted imaging (DWI). ADC was calculated in regions of
      interest defined in the left and right SCP by two clinically blinded operators.
      Intrarater (r = 0.98, P < 0.001) and interrater reliability (r = 0.97; P < 0.001)
      for SCP measurements were high. Patients with PSP had higher SCP rADC values
      (median 0.98 x 10(-3)mm(2)/s) than patients with PD (median 0.79 x 10(-3)
      mm(2)/s, P < 0.001), MSA-P (median 0.79 x 10(-3) mm(2)/s, P < 0.001), and healthy
      controls (median 0.80 x 10(-3) mm(2)/s, P < 0.001). DWI discriminated patients
      with PSP from PD and healthy subjects on the basis of SCP rADC individual values
      (100% sensitivity and specificity) and from patients with MSA-P (96.4%
      sensitivity and 93.3% specificity). The higher values of rADC in SCP of patients
      with PSP correspond with the in vivo microstructural feature of atrophy detected
      postmortem and provide an additional support for early discrimination between PSP
      and other neurodegenerative parkinsonisms.

PMID- 18816804
TI  - Pediatric squamous cell carcinoma arising in an alpha-fetoprotein-producing
      mature cystic teratoma of the mandible.
AB  - Teratomas, most often diagnosed in younger patients, represent the most
      frequently identified subtype of pediatric germ cell tumors. It is very uncommon
      for teratomas to present in the head and neck region and demonstrate malignant
      transformation. We present a case of squamous cell carcinoma arising in an alpha
      fetoprotein-producing cystic teratoma of the mandible in a 2-year-old female that
      is, to the best of our knowledge, the first such published report. The patient
      was treated with surgical excision along with chemotherapy and has remained
      disease-free 2 years after the conclusion of therapy.

PMID- 18816805
TI  - Isolated central nervous system recurrence of acute promyelocytic leukemia in
      children.
AB  - The incidence of isolated central nervous system (iCNS) relapse in pediatric
      acute promyelocytic leukemia (APL) is debated. We analyzed the literature,
      focusing on clinical trials reported since the advent of ATRA use. Only 2/218
      (0.92%) good risk patients (diagnostic WBC <10,000/microl) had truly iCNS
      relapse. This incidence does not support the use of intrathecal CNS prophylaxis
      for all children with APL. We also identified multiple deficiencies in these
      reports. Additional reporting of these events could provide insight into the true
      incidence and pathogenesis of iCNS relapse and might allow for identification of
      risk factors associated with such extramedullary relapse.

PMID- 18816806
TI  - Treating children with acute lymphoblastic leukemia and Down syndrome:
      pharmacokinetics provides insight into vincristine therapy.

PMID- 18816807
TI  - Thalassemia major in a child with Dubowitz syndrome.

PMID- 18816808
TI  - Validation of oxygen extraction fraction measurement by qBOLD technique.
AB  - Measurement of brain tissue oxygen extraction fraction (OEF) in both baseline and
      functionally activated states can provide important information on brain
      functioning in health and disease. The recently proposed quantitative BOLD
      (qBOLD) technique is MRI-based and provides a regional in vivo OEF measurement
      (He and Yablonskiy, MRM 2007, 57:115-126). It is based on a previously developed
      analytical BOLD model and incorporates prior knowledge about the brain tissue
      composition including the contributions from grey matter, white matter,
      cerebrospinal fluid, interstitial fluid and intravascular blood. The qBOLD model
      also allows for the separation of contributions to the BOLD signal from OEF and
      the deoxyhemoglobin containing blood volume (DBV). The objective of this study is
      to validate OEF measurements provided by the qBOLD approach. To this end we use a
      rat model and compare qBOLD OEF measurements against direct measurements of the
      blood oxygenation level obtained from venous blood drawn directly from the
      superior sagittal sinus. The cerebral venous oxygenation level of the rat was
      manipulated by utilizing different anestheisa methods. The study demonstrates a
      very good agreement between qBOLD approach and direct measurements.

PMID- 18816809
TI  - A phase-sensitive method of flip angle mapping.
AB  - A radiofrequency (RF) excitation scheme is presented in which flip angle is
      encoded in the phase of the resulting excitation. This excitation is implemented
      with nonselective hard pulses, and is used to give flip angle maps over three
      dimensional volumes. This phase-sensitive B1 mapping excitation can be combined
      with various acquisition methods such as gradient recalled echo (GRE) and echo
      planar (EP) readouts. Imaging time depends primarily on the readout method, and
      is roughly equivalent to the imaging time of conventional double-angle techniques
      for three-dimensional acquisition. The phase-sensitive method allows imaging over
      a much wider range of flip angles than double-angle methods. Phantom and in vivo
      results are presented comparing the phase-sensitive method with the conventional
      double-angle method, demonstrating the ability of the phase-sensitive method to
      measure a wider range of flip angles than double-angle methods.

PMID- 18816810
TI  - Comprehensive quantification of signal-to-noise ratio and g-factor for image
      based and k-space-based parallel imaging reconstructions.
AB  - Parallel imaging reconstructions result in spatially varying noise amplification
      characterized by the g-factor, precluding conventional measurements of noise from
      the final image. A simple Monte Carlo based method is proposed for all linear
      image reconstruction algorithms, which allows measurement of signal-to-noise
      ratio and g-factor and is demonstrated for SENSE and GRAPPA reconstructions for
      accelerated acquisitions that have not previously been amenable to such
      assessment. Only a simple "prescan" measurement of noise amplitude and
      correlation in the phased-array receiver, and a single accelerated image
      acquisition are required, allowing robust assessment of signal-to-noise ratio and
      g-factor. The "pseudo multiple replica" method has been rigorously validated in
      phantoms and in vivo, showing excellent agreement with true multiple replica and
      analytical methods. This method is universally applicable to the parallel imaging
      reconstruction techniques used in clinical applications and will allow pixel-by
      pixel image noise measurements for all parallel imaging strategies, allowing
      quantitative comparison between arbitrary k-space trajectories, image
      reconstruction, or noise conditioning techniques.

PMID- 18816811
TI  - Exponential excitation pulses for improved water content mapping in the presence
      of background gradients.
AB  - Several water content mapping techniques are based on the acquisition of multiple
      gradient echoes (GE) with different echo times (TE). However, in the presence of
      linear magnetic field gradients G(susc) the signal decay is no longer exponential
      but in the case of a rectangular slice profile weighted by a sinc function,
      giving rise to erroneous initial amplitudes S(0) in monoexponential fitting.
      Generally, it can be shown that the signal decay is weighted by the time profile
      of the excitation pulse. Thus, for an excitation pulse with an exponential time
      profile, i.e., a Lorentzian slice profile, the signal decay remains exponential
      and exponential fitting still yields the correct amplitude S(0). Multiecho GE
      images of a gel phantom and five human volunteers were acquired at 3 T using a
      sinc-shaped and an exponential excitation pulse. In addition, simulations were
      performed to investigate the influence of saturation effects due to distortion of
      the ideal Lorentzian slice profile. A considerable overestimation of S(0) when
      using a sinc-shaped excitation pulse was observed. Errors were greatly reduced
      with an exponential excitation pulse. We thus propose the use of excitation
      pulses with exponential time profile to obtain accurate estimates for S(0) from
      exponential fitting.

PMID- 18816812
TI  - Performance of a miniature high-temperature superconducting (HTS) surface coil
      for in vivo microimaging of the mouse in a standard 1.5T clinical whole-body
      scanner.
AB  - The performance of a 12-mm high-temperature superconducting (HTS) surface coil
      for in vivo microimaging of mice in a standard 1.5T clinical whole-body scanner
      was investigated. Systematic evaluation of MR image quality was conducted on
      saline phantoms with various conductivities to derive the sensitivity improvement
      brought by the HTS coil compared with a similar room-temperature copper coil. The
      observed signal-to-noise ratio (SNR) was correlated to the loaded quality factor
      of the radio frequency (RF) coils and is theoretically validated with respect to
      the noise contribution of the MR acquisition channel. The expected in vivo SNR
      gain was then extrapolated for different anatomical sites by monitoring the
      quality factor in situ during animal imaging experiments. Typical SNR gains of
      9.8, 9.8, 5.4, and 11.6 were found for brain, knee, back, and subcutaneous
      implanted tumors, respectively, over a series of mice. Excellent in vivo image
      quality was demonstrated in 16 min with native voxels down to (59 microm)(3) with
      an SNR of 20. The HTS coil technology opens the way, for the first time at the
      current field strength of clinical MR scanners, to spatial resolutions below 10(
      3) mm(3) in living mice, which until now were only accessible to specialized high
      field MR microscopes.

PMID- 18816813
TI  - Three-frequency RF coil designed for optimized imaging of hyperpolarized, 13C
      labeled compounds.
AB  - Imaging exams involving hyperpolarized, (13)C-labeled compounds require novel RF
      coils for efficient signal utilization. While (13)C coils are required for
      mapping the spatial distribution of the hyperpolarized compounds, imaging/pulsing
      at different frequencies is also needed for scan setup steps prior to the image
      acquisition. Imaging/pulsing at the (1)H frequency is typically used for
      anatomical localization and shimming. Flip angle (FA) calibration, which is
      difficult or impossible to achieve at the (13)C frequency, can be accurately
      performed at the (23)Na frequency using the natural abundance signal that exists
      in any living tissue. We demonstrate here a single RF resonant structure that is
      capable of operating linearly at the (1)H and (23)Na frequencies for scan setup
      steps, and in quadrature at the (13)C frequency for imaging. Images at the three
      resonant frequencies of this coil are presented from an exam involving
      hyperpolarized (13)C compounds in vivo.

PMID- 18816814
TI  - Effects of image noise in muscle diffusion tensor (DT)-MRI assessed using
      numerical simulations.
AB  - Diffusion tensor (DT)-MRI studies of skeletal muscle provide information about
      muscle architecture, microstructure, and damage. However, the effects of noise,
      the diffusion weighting (b)-value, and partial volume artifacts on the estimation
      of the diffusion tensor (D) are unknown. This study investigated these issues
      using Monte Carlo simulations of 3 x 9 voxel regions of interest (ROIs)
      containing muscle, adipose tissue, and intermediate degrees of muscle volume
      fractions (f(M)). A total of 1000 simulations were performed for each of eight b
      values and 11 SNR levels. The dependencies of the eigenvalues (lambda(1-3)), mean
      diffusivity (lambda), and fractional anisotropy (FA), and the angular deviation
      of the first eigenvector from its true value (alpha) were observed. For moderate
      b-values (b = 435-725 s/mm(2)) and f(M) = 1, an accuracy of 5% was obtained for
      lambda(1-3), lambda, and FA with an SNR of 25. An accuracy of 1% was obtained for
      lambda(1-3), lambda, and FA with f(M) = 1 and SNR = 50. For regions with f(M) =
      8/9, 5% accuracy was obtained with SNR = 40. For alpha, SNRs of >or=25 and >or=45
      were required for +/-4.5 degrees uncertainty with f(M) = 1 and f(M) = 0.5,
      respectively; SNR >or= 60 was required for +/-9 degrees uncertainty in single
      muscle voxels. These findings may influence the design and interpretation of DT
      MRI studies of muscle microstructure, damage, and architecture.

PMID- 18816815
TI  - Predictive modeling in glioma grading from MR perfusion images using support
      vector machines.
AB  - The advantages of predictive modeling in glioma grading from MR perfusion images
      have not yet been explored. The aim of the current study was to implement a
      predictive model based on support vector machines (SVM) for glioma grading using
      tumor blood volume histogram signatures derived from MR perfusion images and to
      assess the diagnostic accuracy of the model and the sensitivity to sample size. A
      total of 86 patients with histologically-confirmed gliomas were imaged using
      dynamic susceptibility contrast (DSC) MRI at 1.5T. Histogram signatures from 53
      of the 86 patients were analyzed independently by four neuroradiologists and used
      as a basis for the predictive SVM model. The resulting SVM model was tested on
      the remaining 33 patients and analyzed by a fifth neuroradiologist. At optimal
      SVM parameters, the true positive rate (TPR) and true negative rate (TNR) of the
      SVM model on the 33 patients was 0.76 and 0.82, respectively. The interobserver
      agreement and the TPR increased significantly when the SVM model was based on an
      increasing sample size (P < 0.001). This result suggests that a predictive SVM
      model can aid in the diagnosis of glioma grade from MR perfusion images and that
      the model improves with increasing sample size.

PMID- 18816816
TI  - Gibbs tracking: a novel approach for the reconstruction of neuronal pathways.
AB  - Reconstruction of neuronal fibers using diffusion-weighted (DW) MRI is an
      emerging method in biomedical research. Existing fiber-tracking algorithms are
      commonly based on the "walker principle." Fibers are reconstructed as
      trajectories of "walkers," which are guided according to local diffusion
      properties. In this study, a new method of fiber tracking is proposed that does
      not engage any "walking" algorithm. It resolves a number of inherent problems of
      the "walking" approach, in particular the reconstruction of crossing and
      spreading fibers. In the proposed method, the fibers are built with small line
      elements. Each line element contributes an anisotropic term to the simulated DW
      signal, which is adjusted to the measured signal. This method demonstrates good
      results for simulated fibers. A single in vivo result demonstrates the successful
      reconstruction of the dominant neuronal pathways. A comparison with the diffusion
      tensor imaging (DTI)-based fiber assignment with continuous tracking (FACT)
      method and the probabilistic index of connectivity (PICo) method based on a
      multitensor model is performed for the callosal fibers. The result shows a strong
      increase in the number of reconstructed fibers. These almost fill the total white
      matter (WM) volume and connect a large area of the cortex. The method is very
      computationally expensive. Possible ways to address this problem are discussed.

PMID- 18816817
TI  - Comparative reliability of proton spectroscopy techniques designed to improve
      detection of J-coupled metabolites.
AB  - Improved detection of J-coupled neurometabolites through the use of modified
      proton magnetic resonance spectroscopy (1H-MRS) techniques has recently been
      reported. TE-averaged point-resolved spectroscopy (PRESS) uses the J modulation
      effects by averaging FIDs with differing echo times to improve detection of
      glutamate, while standard PRESS detection of glutamate can be improved by using
      an appropriate single echo determined from J-modulation simulations. In the
      present study, the reliabilities of TE-averaged PRESS, standard PRESS with TE =
      40 ms, and standard PRESS with TE = 30 ms in detecting metabolite levels in the
      cingulate gyrus of the human brain at 3T were compared in six subjects. TE
      averaged PRESS measures showed a mean variability of 9% for N-acetyl aspartate,
      choline, and creatine, compared with < 4% for the 30- and 40-ms PRESS techniques.
      The coefficients of variation for glutamate were 10%, 7%, and 5% for TE-averaged,
      30-ms, and 40-ms PRESS, respectively. PRESS with a TE of 40 ms also demonstrated
      improved reliability for GABA and glutamine concentrations. These results show
      that with the appropriate selection of echo time standard PRESS can be a reliable
      (1)H-MRS technique for the measurement of J-coupled neurometabolites in the human
      brain and, moreover, compares favorably with at least one J-edited technique.

PMID- 18816818
TI  - Four-dimensional transcatheter intraarterial perfusion (TRIP)-MRI for monitoring
      liver tumor embolization in VX2 rabbits.
AB  - Transcatheter intraarterial perfusion (TRIP)-MRI is an intraprocedural technique
      to iteratively monitor liver tumor perfusion changes during transcatheter
      arterial embolization (TAE) and chemoembolization (TACE). However, previous TRIP
      MRI approaches using two-dimensional (2D) T(1)-weighted saturation-recovery
      gradient-recalled echo (GRE) sequences provided only limited spatial coverage and
      limited capacity for accurate perfusion quantification. In this preclinical
      study, a quantitative 4D TRIP-MRI technique (serial iterative 3D volumetric
      perfusion imaging) with rigorous radiofrequency (RF) B(1) field calibration and
      dynamic tissue longitudinal relaxation rate R(1) measurement is presented for
      monitoring intraprocedural liver tumor perfusion during TAE. 4D TRIP-MRI and TAE
      were performed in five rabbits with eight VX2 liver tumors (N = 8). After B(1)
      calibrated baseline and dynamic R(1) quantification, subsequent tissue contrast
      agent concentration time curves were derived. A single-input flow-limited
      pharmacokinetic model and peak gradient method were applied for perfusion
      analysis. The perfusion Frho reduced significantly from pre-TAE 0.477 (95%
      confidence interval [CI]: 0.384-0.570) to post-TAE 0.131 (95% CI: 0.080-0.183
      ml/min/ml, P < 0.001).

PMID- 18816819
TI  - Single-shot 3D GRASE with cylindrical k-space trajectories.
AB  - Development of GRASE (gradient- and spin-echo) pulse sequences for single-shot 3D
      imaging has been motivated by physiologic studies of the brain. The duration of
      echo-planar imaging (EPI) subsequences between RF refocusing pulses in the GRASE
      sequence is determinant of image distortions and susceptibility artifacts. To
      reduce these artifacts the regular Cartesian trajectory is modified to a circular
      trajectory in 2D and a cylindrical trajectory in 3D for reduced echo train time.
      Incorporation of "fly-back" trajectories lengthened the time of the subsequences
      and proportionally increased susceptibility artifact but the unipolar readout
      gradients eliminate all ghost artifacts. The modified cylindrical trajectory
      reduced susceptibility artifact and distortion artifact while raising the signal
      to-noise ratio in both phantom and human brain images.

PMID- 18816820
TI  - Advantage of sampling density weighted apodization over postacquisition filtering
      apodization for sodium MRI of the human brain.
AB  - For sodium imaging of the human brain, Gibbs' ringing can degrade image
      appearance and confound image analysis; k-space filtering is generally required.
      In this work, the signal to noise ratio (SNR) advantage of sampling density
      weighted apodization (SDWA) over uniform k-space sampling with postacquisition
      filtering apodization (UPFA) is quantified for sodium three-dimensional (3D)
      twisted projection imaging (TPI) of the human brain. A direct comparison was
      conducted with the creation of two TPI projection data sets (each with an equal
      number of projections of equal length): one generating uniform sampling density,
      and the other a "generalized Hamming" sampling density that conformed to 3D-TPI
      constraints for full k-space sampling. In this work it is shown theoretically,
      and then experimentally with sodium imaging of the human brain, that an SNR
      advantage of 17% is associated with the use of SDWA over UPFA for the filter
      presented, along with a significant noise-coloring benefit.

PMID- 18816821
TI  - Anesthetic effects on regional CBF, BOLD, and the coupling between task-induced
      changes in CBF and BOLD: an fMRI study in normal human subjects.
AB  - Functional MR imaging was performed in sixteen healthy human subjects measuring
      both regional cerebral blood flow (CBF) and blood oxygen level dependent (BOLD)
      signal when visual and auditory stimuli were presented to subjects in the
      presence or absence of anesthesia. During anesthesia, 0.25 mean alveolar
      concentration (MAC) sevoflurane was administrated. We found that low-dose
      sevoflurane decreased the task-induced changes in both BOLD and CBF. Within the
      visual and auditory regions of interest inspected, both baseline CBF and the task
      induced changes in CBF decreased significantly during anesthesia. Low-dose
      sevoflurane significantly altered the task-induced CBF-BOLD coupling; for a unit
      change of CBF, a larger change in BOLD was observed in the anesthesia condition
      than in the anesthesia-free condition. Low-dose sevoflurane was also found to
      have significant impact on the spatial nonuniformity of the task-induced
      coupling. The alteration of task-induced CBF-BOLD coupling by low-dose
      sevoflurane introduces ambiguity to the direct interpretation of functional MRI
      (fMRI) data based on only one of the indirect measures-CBF or BOLD. Our
      observations also indicate that the manipulation of the brain with an anesthetic
      agent complicates the model-based quantitative interpretation of fMRI data, in
      which the relative task-induced changes in oxidative metabolism are calculated by
      means of a calibrated model given the relative changes in the indirect vascular
      measures, usually CBF and BOLD.

PMID- 18816822
TI  - Kinetic and mechanical analysis of live tube morphogenesis.
AB  - Ribbon is a nuclear Broad Tramtrack Bric-a-brac (BTB) -domain protein required
      for morphogenesis of the salivary gland and trachea. We recently showed that
      ribbon mutants exhibit decreased Crumbs and Rab11-coincident apical vesicles and
      increased apical Moesin activity and microvillar structure during tube
      elongation. To learn how these molecular and morphological changes affect the
      dynamics of tubulogenesis, we optimized an advanced two-photon microscope to
      enable high-resolution live imaging of the salivary gland and trachea. Live
      imaging revealed that ribbon mutant tissues exhibit slowed and incomplete lumenal
      morphogenesis, consistent with previously described apical defects. Because
      Moesin activity correlates with cortical stiffness, we hypothesize that ribbon
      mutants suffer from increased apical stiffness during morphogenesis. We develop
      this hypothesis through mechanical analysis, using the advantages of live imaging
      to construct computational elastic and analytical viscoelastic models of tube
      elongation, which suggest that ribbon mutant tubes exhibit three- to fivefold
      increased apical stiffness and twofold increased effective apical viscosity.

PMID- 18816823
TI  - Analysis of the IKKbeta/NF-kappaB signaling pathway during embryonic
      angiogenesis.
AB  - The nuclear factor-kappaB (NF-kappaB) signaling pathway regulates cellular
      growth, survival, differentiation and development. In this study, the functions
      of IkappaB kinase (IKK)beta in angiogenesis during mouse development were
      examined. Conditional disruption of the Ikkbeta locus in endothelial cells using
      the well-characterized Tie2-Cre transgene resulted in embryonic lethality between
      embryonic day (E) 13.5 and E15.5. Examination of the mutant embryos revealed that
      while deletion of Ikkbeta occurred in endothelial cells throughout the embryo,
      only the vascular network in the fetal liver was affected. Disruption of the
      fetal liver vasculature was accompanied by decreased cell proliferation and
      increased apoptosis of hepatocytes, but hematopoiesis was not affected. Increased
      apoptosis was not observed outside of fetal liver in the mutant embryos. These
      results indicate that the IKKbeta/NF-kappaB pathway plays a previously
      unappreciated role in development of the sinusoidal vasculature in the fetal
      liver and additionally that this pathway is critical in the crosstalk between
      endothelial cells and hepatocytes during mouse development.

PMID- 18816824
TI  - Generation of oocyte-specifically expressed cre transgenic zebrafish for female
      germline excision of loxP-flanked transgene.
AB  - In this communication, we report the generation of a cre transgenic zebrafish
      line under an oocyte-specific promoter, zp3. The transgenic line Tg(zp3:cre;
      krt8:rfp) also contains a co-integrated rfp transgene under the skin epithelial
      promoter krt8 to allow selection of cre transgenic fish based on RFP fluorescence
      in the skin. We demonstrated in this transgenic line that cre mRNA was
      specifically expressed in growing oocytes like endogenous zp3 mRNA. When
      Tg(zp3:cre; krt8:rfp) was crossed with a loxP transgenic line, the floxed DNA was
      specifically eliminated from female, but not male, germline. Tg(zp3:cre;
      krt8:rfp) fish also have maternal cre mRNA in early embryos to cause Cre-mediated
      recombination; this feature can be used to activate other loxP transgenic lines
      in early embryos. Furthermore, after crossing with another loxP transgenic line,
      Tg(EF:loxP-mCherry-loxP-egfp), we confirmed that our cre line was capable of
      activating a loxP-blocked EGFP reporter gene by both maternal and oocyte
      expressed Cre.

PMID- 18816825
TI  - Baf60c is a component of the neural progenitor-specific BAF complex in developing
      retina.
AB  - Remodeling of the chromatin network plays an important role regulating embryonic
      development as well as differentiation. The SWI/SNF complex is an ATP-dependent
      chromatin-remodeling complex. It consists of several proteins, including an
      ATPase subunit, either Brg1 or Brm. Two subunits of this complex, Baf53a and
      Baf45, have been previously identified as being neural progenitor-specific. In
      this study, we show that Baf60c, another important part of this large complex,
      acts in a similar neural progenitor-specific manner. We show that during
      development Baf60c is expressed in neural progenitors in human retinas as well as
      mouse retina, cortex and spinal cord. Baf60c expression is lost during neural
      differentiation and its overexpression keeps the progenitors in a proliferative
      state through its interaction with the Notch pathway. Finally, we show that
      Baf60c is re-expressed in the Muller glial cells that re-enter the cell cycle
      after neurotoxic damage.

PMID- 18816826
TI  - Sex-specific expression of SOX9 during gonadogenesis in the amphibian Xenopus
      tropicalis.
AB  - To investigate the role of SOX9 gene in amphibian gonadogenesis, we analyzed its
      expression during male and female gonadogenesis in Xenopus tropicalis. The
      results showed that in both sexes SOX9 mRNA and protein were first detectable
      after metamorphosis when the gonads were well differentiated and remained present
      until the adult stage. In the testis, SOX9 expression was restricted to the
      nucleus of Sertoli-like cells, similarly to what has been observed in other
      vertebrates suggesting a conserved role in vertebrate testicular differentiation.
      In the ovary, in sharp contrast with what has been observed in all vertebrates
      examined so far, the SOX9 protein was localized in the cytoplasm of
      previtellogenic oocytes before being translocated into the nucleus of
      vitellogenic oocytes suggesting an unexpected role during oogenesis. These
      results suggest that the SOX9 gene may not be a sex-determining gene in X.
      tropicalis and may play different functions in testicular and ovarian
      differentiation.

PMID- 18816827
TI  - Estimation of the orientation distribution function from diffusional kurtosis
      imaging.
AB  - The Orientation Distribution Function (ODF) is used to describe the
      directionality of multimodal diffusion in regions with complex fiber architecture
      present in brain and other biological tissues. In this study, an approximation
      for the ODF of water diffusion from diffusional kurtosis imaging (DKI) is
      presented. DKI requires only a relatively limited number of diffusion
      measurements and, for the brain, b values no higher than 2500 s/mm(2). The DKI
      based ODF approximation is decomposed into two components representing the
      Gaussian and non-Gaussian (NG) diffusion contributions, respectively. Simulations
      of multiple fiber configurations show that both the total and the NG-ODF are able
      to resolve the orientations of the component fibers, with the NG-ODF being the
      most sensitive to profiling the fibers' directions. Orientation maps obtained for
      in vivo brain imaging data demonstrate multiple fiber components in brain regions
      with complex anatomy. The results appear to be in agreement with known white
      matter architecture.

PMID- 18816828
TI  - Myoinositol content in the human brain is modified by transcranial direct current
      stimulation in a matter of minutes: a 1H-MRS study.
AB  - Brain content of myoinositol (mI) has been shown to be altered in several
      neuropsychiatric conditions. Likewise, various forms of electric currents have
      been applied to the human brain for therapeutic purposes in neuropsychiatric
      diseases. In this study we aimed to depict the effects of low-power transcranial
      direct current stimulation (tDCS) on brain mI by proton magnetic resonance
      spectroscopy ((1)H-MRS). We studied two groups of five healthy subjects by (1)H
      MRS: the first group was studied before and after both anodal and sham (placebo)
      tDCS over the right frontal lobe, and the second group was studied at the same
      intervals without undergoing either sham or anodal tDCS. Anodal tDCS induced a
      significant increase of mI content at 30 min after stimulation offset (141.5 +/-
      16.7%, P < 0.001) below the stimulating electrode but not in distant regions,
      such as the visual cortex, whereas sham tDCS failed to induce changes in mI.
      Neither N-acetyl-aspartate (NAA) nor the other metabolite contents changed after
      anodal or sham stimulation. (1)H-MRS represents a powerful tool to follow the
      regional effects of tDCS on brain mI and, possibly, on the related
      phosphoinositide system.

PMID- 18816829
TI  - Three-dimensional high-resolution magnetic resonance spectroscopic imaging for
      absolute quantification of 31P metabolites in human liver.
AB  - Liver dysfunction correlates with alterations of intracellular concentrations of
      (31)P metabolites. Localization and absolute quantification should help to trace
      regional hepatic metabolism. An improved protocol for the absolute quantification
      of (31)P metabolites in vivo in human liver was developed by employing three
      dimensional (3D) k-space weighted spectroscopic imaging (MRSI) with B(1)
      insensitive adiabatic excitation. The protocol allowed for high spatial
      resolution of 17.8 +/- 0.22 cm(3) in 34 min at 3 T. No pulse adjustment prior to
      MRSI measurement was necessary due to adiabatic excitation. The protocol geometry
      was identical for all measurements so that one calibration data set, acquired
      from phantom replacement measurement, was applied for all quantifications. The
      protocol was tested in 10 young, healthy volunteers, for whom 57 +/- 7 spectra
      were quantified. Concentrations per liter of liver volume (reproducibilities)
      were 2.24 +/- 0.10 mmol/L (1.8%) for phosphomonoesters (PME), 1.37 +/- 0.07
      mmol/L (7.9%) for inorganic phosphate (Pi), 11.40 +/- 0.96 mmol/L (2.9%) for
      phosphodiesters (PDE), and 2.14 +/- 0.10 mmol/L (1.6%) for adenosine triphosphate
      (ATP), respectively. Taken together, this approach provides fast, simple, and
      reproducible high-resolution absolute quantification and detailed mapping of the
      spatial distribution of hepatic (31)P metabolites. This method allows for
      examination of regional deviations of energy metabolism in human liver diseases.

PMID- 18816830
TI  - New "multicolor" polypeptide diamagnetic chemical exchange saturation transfer
      (DIACEST) contrast agents for MRI.
AB  - An array of 33 prototype polypeptides was examined as putative contrast agents
      that can be distinguished from each other based on the chemical exchange
      saturation transfer (CEST) mechanism. These peptides were chosen based on
      predictions of the chemical exchange rates of exchangeable amide, amine, and
      hydroxyl protons that produce this contrast, and tested at 11.7T for their CEST
      suitability. Artificial colors were assigned to particular amino acid units
      (lysine, arginine, threonine, and serine) based on the separate resonance
      frequencies of these exchangeable protons. The magnitude of the CEST effect could
      be fine-tuned by altering the amino acid sequence, and these three exchangeable
      groups could be distinguished in an MR phantom based on their different chemical
      shifts ("colors"). These new diamagnetic CEST (DIACEST) agents possess a wide
      range of electrostatic charges, compositions, and protein stabilities in vivo,
      making them potentially suitable for a variety of biological applications such as
      designing MR reporter genes for imaging cells and distinguishing multiple targets
      within the same MR image.

PMID- 18816831
TI  - Age dependence of regional proton metabolites T2 relaxation times in the human
      brain at 3 T.
AB  - Although recent studies indicate that use of a single global transverse
      relaxation time, T(2), per metabolite is sufficient for better than +/-10%
      quantification precision at intermediate and short echo-time spectroscopy in
      young adults, the age-dependence of this finding is unknown. Consequently, the
      age effect on regional brain choline (Cho), creatine (Cr), and N-acetylaspartate
      (NAA) T(2)s was examined in four age groups using 3D (four slices, 80 voxels 1
      cm(3) each) proton MR spectroscopy in an optimized two-point protocol. Metabolite
      T(2)s were estimated in each voxel and in 10 gray and white matter (GM, WM)
      structures in 20 healthy subjects: four adolescents (13 +/- 1 years old), eight
      young adults (26 +/- 1); two middle-aged (51 +/- 6), and six elderly (74 +/- 3).
      The results reveal that T(2)s in GM (average +/- standard error of the mean) of
      adolescents (NAA: 301 +/- 30, Cr: 162 +/- 7, Cho: 263 +/- 7 ms), young adults
      (NAA: 269 +/- 7, Cr: 156 +/- 7, Cho: 226 +/- 9 ms), and elderly (NAA: 259 +/- 13,
      Cr: 154 +/- 8, Cho: 229 +/- 14 ms), were 30%, 16%, and 10% shorter than in WM,
      yielding mean global T(2)s of NAA: 343, Cr: 172, and Cho: 248 ms. The elderly
      NAA, Cr, and Cho T(2)s were 12%, 6%, and 10% shorter than the adolescents, a
      change of under 1 ms/year assuming a linear decline with age. Formulae for T(2)
      age-correction for higher quantification precision are provided.

PMID- 18816832
TI  - In vivo quantification of transvascular water exchange during the acute phase of
      permanent stroke.
AB  - Mechanisms that underlie early ischemic damages to the blood-brain-barrier (BBB)
      are not well understood. This study presents a novel magnetic resonance imaging
      (MRI) technique using a widely available pulse sequence and a long-circulating
      intravascular contrast agent to quantify water movements across the BBB at early
      stages of stroke progression. We characterized the integrity of the BBB by
      measuring the flip angle dependence of the water exchange-affected MRI signal
      intensity, to generate an efficient quantitative index of vascular permeability
      (WEI, or water exchange index). We performed in vivo MRI experiments to measure
      the transvascular WEI immediately after the permanent filament occlusion of the
      middle cerebral artery of mice (n = 5), in which we monitored changes in blood
      volume (V(b)), apparent diffusion coefficient (ADC), and intra-/extravascular WEI
      for 4 hours. Statistically significant elevations (P < 0.05) of WEI in the
      ischemic tissue were observed as early as 1 hour after ischemic onset. Initial
      reduction of the apparent blood volume (V(app)) in the infarct cortex was
      followed by a continuous increase of V(app) over time. Although the measured ADC
      in the ipsilesional cortex continuously decreased, the abnormally high intra
      /extravascular WEI remained constant at a significantly elevated level,
      indicating apparent BBB injury at this early stage of stroke.

PMID- 18816833
TI  - Design and use of tailored hard-pulse trains for uniformed saturation of
      myocardium at 3 Tesla.
AB  - Complete and uniform saturation of myocardium is essential for quantitative
      myocardial perfusion imaging using the first pass of a contrast agent. At 3 T,
      inhomogeneities of both the static (B(0)) and radiofrequency (B(1)) magnetic
      fields have led to the use of adiabatic B(1)-insensitive rotation type 4 (BIR-4)
      pulses, which in practice are constrained by radiofrequency (RF) heating. In this
      study, we propose the use of trains of weighted hard pulses that are optimized
      for the measured variation of B(0) and B(1) fields in the myocardium. These
      pulses are simple to design, and require substantially lower RF power when
      compared with BIR-4 pulses. In volunteers, at 3 T, we demonstrated that the
      proposed saturation pulse with three subpulses results in lower peak and lower
      average residual longitudinal magnetization over the heart, as compared with 8
      msec BIR-4 pulses and conventional hard pulse trains (P < 0.05).

PMID- 18816834
TI  - Quantitative MR susceptibility mapping using piece-wise constant regularized
      inversion of the magnetic field.
AB  - Magnetic properties characterized by susceptibility and chemical shift linearly
      modify the local magnetic field experienced by spins. A piece-wise constant
      solution using magnetic resonance imaging is found to the challenging inversion
      problem from field to magnetic properties. The magnetic field shifts were
      estimated from MR phase images. The MR magnitude images were segmented into many
      regions of uniform magnetic properties. Standard linear regression using the
      calculated magnetic field from each region allowed accurate susceptibility
      quantification. The technique was experimentally validated on a variety of
      samples including water, vegetable oil, air, Gadolinium, and superparamagnetic
      iron oxides. Susceptibility was measured with a precision better than 0.1 ppm, in
      a range of 10 ppm. In vivo feasibility was shown on the forearm for which soft
      tissue, cortical bone, and bone marrow susceptibility, and chemical shift values
      in good agreement with literature data were obtained.

PMID- 18816835
TI  - VEGF-mediated fusion in the generation of uniluminal vascular spheroids.
AB  - Embryonic mouse allantoic tissue (E8.5) was cultured in hanging drops to generate
      a three-dimensional vascular micro-tissue. The resulting tissue spheroids had an
      inner network of small diameter vessels expressing platelet endothelial cell
      adhesion molecule-1 (PECAM-1) and an outer layer of cells expressing SMalphaA,
      SM22-alpha, and SM-MHC. In a subsequent phase of culture, the fusion-promoting
      activity of vascular endothelial growth factor (VEGF) was used to transform the
      inner network of small diameter endothelial tubes into a contiguous layer of
      cells expressing PECAM-1, CD34, and VE-cadherin that circumscribed a central
      lumen-like cavity. The blood vessel-like character of the VEGF-treated spheroids
      was further demonstrated by their physiologically relevant vasodilatory and
      contractile responses, including contraction induced by KCl and relaxation
      stimulated by high-density lipoproteins and acetylcholine-induced nitric oxide
      production.

PMID- 18816836
TI  - Mouse Fem1b interacts with the Nkx3.1 homeoprotein and is required for proper
      male secondary sexual development.
AB  - Previous studies of epithelial cell growth and differentiation in the prostate
      gland have identified the homeodomain protein Nkx3.1 as a central regulator of
      prostate development and carcinogenesis. To understand the molecular mechanisms
      of Nkx3.1 function, we have used yeast two-hybrid analysis to identify Nkx3.1
      interacting proteins, and have isolated Fem1b, a mammalian homolog of the C.
      elegans sex-determining gene Fem-1. In mice, the Fem1b and Nkx3.1 genes encode
      proteins that interact in glutathione-S-transferase (GST) pull-down and co
      immunoprecipitation assays, and are co-expressed in the prostate and testis of
      neonatal mice. Null mutants for Fem1b generated by gene targeting display defects
      in prostate ductal morphogenesis and secretory protein expression, similar to
      phenotypes found in Nkx3.1 mutants. We propose that Fem1b may have a conserved
      role in the generation of sexual dimorphism through its interaction with Nkx3.1
      in the developing prostate gland.

PMID- 18816837
TI  - Essential role for fibrillin-2 in zebrafish notochord and vascular morphogenesis.
AB  - Recent studies demonstrate that lysyl oxidase cuproenzymes are critical for
      zebrafish notochord formation, but the molecular mechanisms of copper-dependent
      notochord morphogenesis are incompletely understood. We, therefore, conducted a
      forward genetic screen for zebrafish mutants that exhibit notochord sensitivity
      to lysyl oxidase inhibition, yielding a mutant with defects in notochord and
      vascular morphogenesis, puff daddygw1 (pfdgw1). Meiotic mapping and cloning
      reveal that the pfdgw1 phenotype results from disruption of the gene encoding the
      extracellular matrix protein fibrillin-2, and the spatiotemporal expression of
      fibrillin-2 is consistent with the pfdgw1 phenotype. Furthermore, each aspect of
      the pfdgw1 phenotype is recapitulated by morpholino knockdown of fibrillin-2.
      Taken together, the data reveal a genetic interaction between fibrillin-2 and the
      lysyl oxidases in notochord formation and demonstrate the importance of fibrillin
      2 in specific early developmental processes in zebrafish.

PMID- 18816838
TI  - Development of lymphatic vessels in mouse embryonic and early postnatal hearts.
AB  - We aimed to study the spatiotemporal pattern of lymphatic system formation in the
      embryonic and early postnatal mouse hearts. The first sign of the development of
      lymphatics are Lyve-1-positive cells located on the subepicardial area. Strands
      of Lyve-1-positive cells occur first along the atrioventricular sulcus of the
      diaphragmatic surface and then along the great arteries. Lumenized tubules
      appear, arranged in rows or in a lattice. They are more conspicuous in dorsal
      atrioventricular junction, along the major venous and coronary artery branches
      and at the base of the aorta and the pulmonary trunk extending toward the heart
      apex. At later stages, some segments of the lymphatic vessels are partially
      surrounded by smooth muscle cells. Possible mechanisms of lymphangiogenesis are:
      addition of Lyve-1-positive cells to the existing tubules, elongation of the
      lymphatic lattice, sprouting and coalescence of tubules. We discuss the existence
      of various subpopulations of endothelial cells among the Lyve-1-positive cells.

PMID- 18816840
TI  - Leading edge-secreted Dpp cooperates with ACK-dependent signaling from the
      amnioserosa to regulate myosin levels during dorsal closure.
AB  - Dorsal closure of the Drosophila embryo is an epithelial fusion in which the
      epidermal flanks migrate to close a hole in the epidermis occupied by the
      amnioserosa, a process driven in part by myosin-dependent cell shape change. Dpp
      signaling is required for the morphogenesis of both tissues, where it promotes
      transcription of myosin from the zipper (zip) gene. Drosophila has two members of
      the activated Cdc42-associated kinase (ACK) family: DACK and PR2. Overexpression
      of DACK in embryos deficient in Dpp signaling can restore zip expression and
      suppress dorsal closure defects, while reducing the levels of DACK and PR2
      simultaneously using mutations or amnioserosa-specific knock down by RNAi results
      in loss of zip expression. ACK function in the amnioserosa may generate a signal
      cooperating with Dpp secreted from the epidermis in driving zip expression in
      these two tissues, ensuring that cell shape changes in dorsal closure occur in a
      coordinated manner.

PMID- 18816841
TI  - Androgen receptor gene expression in the developing and adult zebrafish brain.
AB  - Androgens play a central role in the regulation of male sexual differentiation
      and behavior in many vertebrates, including zebrafish. Their signaling is
      mediated by activation of the androgen receptor. A single androgen receptor (ar)
      gene was recently identified in zebrafish, which encodes a protein that binds
      androgens in vitro. However, the tissue-specific expression pattern of this
      receptor in vivo has not been described. Using whole-mount RNA in situ
      hybridization, we characterized expression of the ar gene in developing zebrafish
      and in the adult brain. In embryos, transcripts were found in the presumptive
      pronephros and in olfactory placodes. By 3-5 days postfertilization, ar
      transcripts were also detected in the pineal organ anlage and the retina. In the
      adult brain, ar was expressed in discrete regions of the telencephalon, in the
      preoptic area, and throughout the periventricular hypothalamus, regions
      previously implicated in the regulation of sexually dimorphic behaviors in
      mammals.

PMID- 18816842
TI  - Comparison of delayed gadolinium enhanced MRI of cartilage (dGEMRIC) using
      inversion recovery and fast T1 mapping sequences.
AB  - The delayed Gadolinium Enhanced MRI of Cartilage (dGEMRIC) technique has shown
      promising results in pilot clinical studies of early osteoarthritis. Currently,
      its broader acceptance is limited by the long scan time and the need for
      postprocessing to calculate the T1 maps. A fast T1 mapping imaging technique
      based on two spoiled gradient echo images was implemented. In phantom studies, an
      appropriate flip angle combination optimized for center T1 of 756 to 955 ms
      yielded excellent agreement with T1 measured using the inversion recovery
      technique in the range of 200 to 900 ms, of interest in normal and diseased
      cartilage. In vivo validation was performed by serially imaging 26 hips using the
      inversion recovery and the Fast 2 angle T1 mapping techniques (center T1 756 ms).
      Excellent correlation with Pearson correlation coefficient R2 of 0.74 was seen
      and Bland-Altman plots demonstrated no systematic bias.

PMID- 18816843
TI  - Toward understanding the morphogenesis of siliceous spicules in freshwater
      sponge: differential mRNA expression of spicule-type-specific silicatein genes in
      Ephydatia fluviatilis.
AB  - Siliceous spicules of sponges are morphologically diverse and provide good models
      for understanding the morphogenesis of biomineralized products. The silica
      deposition enzyme silicatein is a component of siliceous spicules of sponges and
      is thought to be the key molecule determining the morphology of spicules. Here,
      we focused on the silicateins of the freshwater sponge Ephydatia fluviatilis,
      which has two types of morphologically and functionally different spicules,
      called megascleres and gemmoscleres. We isolated six isoforms of silicateins and
      examined their mRNA expression in the cells producing megascleres and
      gemmoscleres. The spicule-type-specific mRNA expression of these isoforms and
      differential expression during spicule development suggest that the
      characteristic morphology of spicules is due to the specific properties and
      combinatory functions of silicatein isoforms.

PMID- 18816844
TI  - Development of the proepicardium in Xenopus laevis.
AB  - The proepicardium (PE) is an embryonic progenitor cell population, which provides
      the epicardium, the majority of the cardiac interstitium, the coronary
      vasculature and possibly some cardiomyocytes. Recent studies have documented (1)
      the presence of bilaterally paired PE anlagen in several vertebrates, and (2)
      species-specific differences in the fate of the left and right PE anlagen. Here,
      we document PE development in Xenopus laevis (stages 37-46). The PE appears at
      stage 41 in the form of a cone-shaped accumulation of mesothelial cells covering
      the pericardial surface of the right horn of the sinus venosus. No such structure
      appears on the left sinus horn. At the end of stage 41, the tip of the PE
      establishes a firm contact with the developing ventricle. A secondary tissue
      bridge is established facilitating the transfer of PE cells to the heart. During
      stages 41-46, this tissue bridge is visible in vivo through the transparent body
      wall. Corresponding to the morphological data, the PE marker gene Tbx18 is
      expressed only on the right sinus horn suggesting a right-sided origin of the PE.
      Left-right lineage tracing has confirmed this idea. These results show that
      Xenopus PE development proceeds in a bilaterally asymmetric pattern as previously
      observed in chicks. We speculate that asymmetric PE development is controlled by
      signals from left-right signaling pathways and that the PE is an indicator for
      right-sidedness in Xenopus embryos. Xenopus might be a good model to uncover the
      role of left-right signaling pathways in the control of asymmetric PE
      development.

PMID- 18816845
TI  - Dynamic GATA6 expression in primitive endoderm formation and maturation in early
      mouse embryogenesis.
AB  - The derivation of the primitive endoderm layer from the pluripotent cells of the
      inner cell mass is one of the earliest differentiation and morphogenic events in
      embryonic development. GATA4 and GATA6 are the key transcription factors in the
      formation of extraembryonic endoderms, but their specific contribution to the
      derivation of each endoderm lineage needs clarification. We further analyzed the
      dynamic expression and mutant phenotypes of GATA6 in early mouse embryos. GATA6
      and GATA4 are both expressed in primitive endoderm cells initially. At embryonic
      day (E) 5.0, parietal endoderm cells continue to express both GATA4 and GATA6;
      however, visceral endoderm cells express GATA4 but exhibit a reduced expression
      of GATA6. By and after E5.5, visceral endoderm cells no longer express GATA6. We
      also found that GATA6 null embryos did not form a morphologically recognizable
      primitive endoderm layer, and subsequently failed to form visceral and parietal
      endoderms. Thus, the current study establishes that GATA6 is essential for the
      formation of primitive endoderm, at a much earlier stage then previously
      recognized, and expression of GATA6 discriminates parietal endoderm from visceral
      endoderm lineages.

PMID- 18816846
TI  - Maternal Tgif1 regulates nodal gene expression in Xenopus.
AB  - In Xenopus, the maternal transcription factor VegT is necessary and sufficient to
      initiate the expression of nodal-related genes, which are central to many aspects
      of early development. However, little is known about regulation of VegT activity.
      Using maternal loss-of-function experiments, we show that the maternal
      homeoprotein, Tgif1, antagonizes VegT and plays a central role in anteroposterior
      patterning by negatively regulating a subset of nodal-related genes. Depletion of
      Tgif1 causes the anteriorization of embryos and the up-regulation of nodal
      paralogues nr5 and nr6. Furthermore, Tgif1 inhibits activation of nr5 by VegT in
      a manner that requires a C-terminal Sin3 corepressor-interacting domain. Tgif1
      has been implicated in the transcriptional corepression of transforming growth
      factor-beta (TGFbeta) and retinoid signaling. However, we show that Tgif1 does
      not inhibit these pathways in early development. These results identify an
      essential role for Tgif1 in the control of nodal expression and provide insight
      into Tgif1 function and mechanisms controlling VegT activity.

PMID- 18816847
TI  - Development of diverse lateral line patterns on the teleost caudal fin.
AB  - The lateral line is composed of mechanoreceptors, the neuromasts, which are
      distributed over the body surfaces of fish. We examine the development of
      neuromast patterns on the caudal fins of medaka and zebrafish. In medaka, the
      terminal neuromast is established just prior to the caudal fin formation. The
      terminal neuromast subsequently gives rise to a cluster of accessory neuromasts.
      In zebrafish, the terminal neuromasts vary in terms of both number and position,
      and they achieve their final positions relative to the caudal fin structures
      through migration. Subsequently, they give rise to four lines of accessory
      neuromasts that extend along the caudal fin. We show that developmental processes
      similar to those observed in medaka and zebrafish may account for a large variety
      of patterns in other teleost species. These results establish terminal neuromast
      patterning as a new model for the study of the developmental mechanisms
      underlying diverse lateral line patterns.

PMID- 18816849
TI  - Fgf16 is required for cardiomyocyte proliferation in the mouse embryonic heart.
AB  - Fibroblast growth factor (Fgf) signaling plays important roles in development and
      metabolism. Mouse Fgf16 was predominantly expressed in cardiomyocytes. To
      elucidate the physiological roles of Fgf16, we generated Fgf16 knockout mice.
      Although the mice were apparently normal and fertile, heart weight and
      cardiomyocyte cell numbers were slightly decreased at 6 months of age. However,
      blood pressure, heart rate, and cardiac performance were essentially unchanged.
      In addition, the expression of most cardiac marker genes examined was also
      essentially unchanged. However, the expression of Bnp was significantly
      decreased, indicating potential roles of Fgf16 in the heart under pathological
      conditions. In contrast, the proliferation of embryonic cardiomyocytes was
      significantly decreased, indicating that Fgf16 is a growth factor for these
      cells. The embryonic heart phenotype is similar to that of the Fgf9 knockout
      heart, indicating Fgf9 and Fgf16 to synergistically act as growth factors for
      embryonic cardiomyocytes.

PMID- 18816850
TI  - Altered white matter diffusion anisotropy in normal and preterm infants at term
      equivalent age.
AB  - To investigate white matter (WM) development, voxelwise analyses of diffusion
      tensor MRI (DTMRI) data, acquired from 12 very preterm and 11 preterm infants
      with gestational ages (GA) ranging from 25 to 29 and 29 to 32 weeks,
      respectively, and 10 newborn normal term infants were performed. T(2) relaxation
      measures were also generated to assess brain water content. Compared with newborn
      term infants, very preterm infants were found to possess reduced fractional
      anisotropy (FA) within the frontal lobe, and a number of anterior and posterior
      commissural pathways. Preterm infants possessed reduced FA mainly within the
      posterior regions of the corpus callosum. Unexpectedly, we observed significantly
      reduced FA and increased T(2) within a number of corticospinal projections in the
      newborn term infants compared to the preterm groups. This finding may reflect
      increased water concentration and/or a lowering of FA due to the presence of
      crossing interhemispheric WM projections. These findings indicate that care
      should be taken when interpreting FA indices without knowledge of the possible
      effects of water concentration in the newborn infant brain.

PMID- 18816851
TI  - The developmental sequence of gene expression within the rod photoreceptor
      lineage in embryonic zebrafish.
AB  - In postembryonic zebrafish, rod photoreceptors are continuously generated from
      progenitors in the inner nuclear layer, which are derived from radial Muller glia
      that express the transcription factor pax6. We used BrdU incorporation, in
      combination with in situ hybridization for cell-specific transcription factors,
      to establish the patterns of gene expression during rod lineage maturation in the
      embryonic zebrafish. Downregulation of pax6 expression was accompanied by
      sporadic upregulation of expression of the transcription factors NeuroD/nrd, rx1,
      crx, and Nr2e3/pnr. As cells of the rod lineage entered the outer nuclear layer,
      they became homogeneous, coordinately expressing NeuroD, rx1, crx, and Nr2e3.
      Postmitotic, maturing rods also expressed nrl, rod opsin, and rod
      transducin/gnat1. The presence of rx1 within the rod lineage and in maturing rods
      indicates that rx1 is not cone-specific, as previously reported, and suggests a
      high degree of molecular similarity between rod and cone progenitor populations
      in the zebrafish.

PMID- 18816853
TI  - Properties of branchiomeric and somite-derived muscle development in Tbx1 mutant
      embryos.
AB  - Vertebrate craniofacial and trunk myogenesis are regulated by distinct genetic
      programs. Tbx1, homologue of the del22q11.2 syndrome candidate gene TBX1,
      controls branchiomeric craniofacial muscle development. Here, we demonstrate
      using immunohistochemistry that myogenic regulatory factors are activated in Tbx1
      positive cells within pharyngeal mesoderm. These cells are also Islet1 and
      Capsulin-positive and in the absence of Tbx1 persist in the core of the first
      arch. Sporadic hypoplastic mandibular muscles in Tbx1-/- embryos contain Pax7
      positive myocytes with indistinguishable differentiation properties from wild
      type muscles and have normal tendon attachments and fiber-type patterning. In
      contrast to TBX1 haploinsufficient del22q11.2 syndrome patients, no alteration in
      fiber-type distribution was detected in Tbx1+/- adult masseter and pharyngeal
      constrictor muscles. Furthermore, Tbx1-expressing limb muscles display normal
      patterning, differentiation, fiber-type growth, fiber-type distribution and fetal
      maturation in the absence of Tbx1. The critical requirement for Tbx1 during
      muscle development is thus in the robust onset of myogenic specification in
      pharyngeal mesoderm.

PMID- 18816852
TI  - How degrading: Cyp26s in hindbrain development.
AB  - The vitamin A derivative retinoic acid performs many functions in vertebrate
      development and is thought to act as a diffusible morphogen that patterns the
      anterior-posterior axis of the hindbrain. Recent work in several systems has led
      to insights into how the spatial distribution of retinoic acid is regulated.
      These have shown local control of synthesis and degradation, and computational
      models suggest that degradation by the Cyp26 enzymes plays a critical role in the
      formation of a morphogen gradient as well as its ability to compensate for
      fluctuations in RA levels.

PMID- 18816854
TI  - Gli3-deficient mice exhibit cleft palate associated with abnormal tongue
      development.
AB  - Palatogenesis depends on appropriate growth, elevation, and fusion of the palatal
      shelves and aberration in these processes can lead to palatal clefting. We
      observed a high incidence of palate clefting in mice deficient in Gli3, known for
      its role as a repressor in the absence of Shh signaling. In contrast with several
      current mouse models of cleft palate, Meckel's cartilage extension, cranial
      neural crest migration, palatal shelf proliferation, apoptosis, and key signaling
      components mediated by Shh, Bmp, Fgf, and Tgfbeta, appeared unaffected in Gli3-/-
      mice. Palatal clefting in Gli3-/- mice was consistently associated with tongue
      abnormalities such as failure to flatten and improper positioning, implicating a
      critical role of Gli3 and normal tongue morphogenesis for timely palatal shelf
      elevation and joining. Furthermore, Gli3-/- palatal shelves grown in roller
      cultures without tongue can fuse suggesting that the abnormal tongue is likely an
      impediment for palatal shelf joining in Gli3-/- mutants.

PMID- 18816855
TI  - Thyroid hormone-up-regulated hedgehog interacting protein is involved in larval
      to-adult intestinal remodeling by regulating sonic hedgehog signaling pathway in
      Xenopus laevis.
AB  - Sonic hedgehog (Shh) was previously shown to be involved in the larval-to-adult
      remodeling of the Xenopus laevis intestine. While Shh is transcriptionally
      regulated by thyroid hormone (TH), the posttranscriptional regulation of Shh
      signaling during intestinal remodeling is largely unknown. In the present study,
      we focused on a role of the pan-hedgehog inhibitor, hedgehog interacting protein
      (Hip), in the spatiotemporal regulation of Shh signaling. Using real-time reverse
      transcriptase-polymerase chain reaction and in situ hybridization, we show that
      Hip expression is transiently up-regulated during both natural and TH-induced
      metamorphosis and that Hip mRNA is localized in the connective tissue adjacent to
      the adult epithelial primordia expressing Shh. Interestingly, the expression of
      bone morphogenetic protein-4, a Shh target gene, is hardly detectable where Hip
      is strongly expressed. Finally, we demonstrate that Hip binds to the N-terminal
      fragment of processed Shh in vivo, suggesting that Hip suppresses Shh signaling
      through sequestering Shh.

PMID- 18816856
TI  - Drosophila SIN3 is required at multiple stages of development.
AB  - SIN3 is a component of a histone deacetylase complex known to be important for
      transcription repression. While multiple isoforms of SIN3 have been reported,
      little is known about their relative expression or role in development. Using a
      combination of techniques, we have determined that SIN3 is expressed throughout
      the Drosophila life cycle. The pattern of expression for each individual isoform,
      however, is distinct. Knock down of all SIN3 expression reveals a requirement for
      this protein in embryonic and larval periods. Taken together, the data suggest
      that SIN3 is required for multiple developmental events during the Drosophila
      life cycle.

PMID- 18816857
TI  - Temporal and spatial expression of collagens during murine atrioventricular heart
      valve development and maintenance.
AB  - Heart valve function is achieved by organization of matrix components including
      collagens, yet the distribution of collagens in valvular structures is not well
      defined. Therefore, we examined the temporal and spatial expression of select
      fibril-, network-, beaded filament-forming, and FACIT collagens in endocardial
      cushions, remodeling, maturing, and adult murine atrioventricular heart valves.
      Of the genes examined, col1a1, col2a1, and col3a1 transcripts are most highly
      expressed in endocardial cushions. Expression of col1a1, col1a2, col2a1, and
      col3a1 remain high, along with col12a1 in remodeling valves. Maturing neonate
      valves predominantly express col1a1, col1a2, col3a1, col5a2, col11a1, and col12a1
      within defined proximal and distal regions. In adult valves, collagen protein
      distribution is highly compartmentalized, with ColI and ColXII observed on the
      ventricular surface and ColIII and ColVa1 detected throughout the leaflets.
      Together, these expression data identify patterning of collagen types in
      developing and maintained heart valves, which likely relate to valve structure
      and function.

PMID- 18816858
TI  - Retinoic acid down-regulates Tbx1 expression and induces abnormal differentiation
      of tongue muscles in fetal mice.
AB  - Excess retinoic acid (RA) during pregnancy can cause various developmental
      anomalies in both humans and rodents. We investigated the mechanisms underlying
      the aberrant differentiation of tongue muscles in fetal mice exposed to exogenous
      RA in utero. RA-degrading enzymes (Cyp26a1 and Cyp26b1) were expressed at early
      stages of normal tongue development, but exogenous RA perturbed their expression
      in the fetal tongue. RA is normally distributed in the developing tongue muscles
      but its localization was disrupted by exogenous RA. After RA treatment, myogenic
      determination factors were reduced and the differentiation was significantly
      suppressed in tongue muscles. Tbx1, a candidate gene of DiGeorge syndrome, was
      down-regulated in the fetal tongue in response to excess RA. Moreover, Tbx1 as
      well as myogenic determination factors were not observed in tongue muscle
      primordia of Cyp26b1-/- fetuses. Our study suggests that RA signaling may play an
      essential role in tongue muscle differentiation via the regulation of Tbx1.

PMID- 18816860
TI  - Perplexing Pax: from puzzle to paradigm.
AB  - Pax transcription factors are critical for the development of the central nervous
      system (CNS) where they have a biphasic role, initially dictating CNS
      regionalization, while later orchestrating differentiation of specific cell
      subtypes. While a plethora of expression, misexpression, and mutation studies
      lend support for this argument and clarify the importance of Pax genes in CNS
      development, less well understood, and more perplexing, is the continued Pax
      expression in the adult CNS. In this article we explore the mechanism of action
      of Pax genes in general, and while being cognizant of existing developmental
      data, we also draw evidence from (1) adult progenitor cells involved in
      regeneration and tissue maintenance, (2) specific expression patterns in fully
      differentiated adult cells, and (3) analysis of direct target genes functioning
      downstream of Pax proteins. From this, we present a more encompassing theory that
      Pax genes are key regulators of a cell's measured response to a dynamic
      environment.

PMID- 18816863
TI  - Primer and interview: epithelial to mesenchymal transition. [Interview by Julie
      Kiefer].
AB  - A complex body plan would not be possible without the evolution of the epithelial
      to mesenchymal (EMT) transition. This primer introduces the hallmarks of EMT,
      molecular mechanisms underlying the process, and its role in development and
      disease. Accompanying the primer is a discussion of current topics in the field
      with EMT experts Angela Nieto, Ph.D., and Jean Paul Thiery, Ph.D.

PMID- 18816861
TI  - Inhibition of mammalian muscle differentiation by regeneration blastema extract
      of Sternopygus macrurus.
AB  - Tissue regeneration through stem cell activation and/or cell dedifferentiation is
      widely distributed across the animal kingdom. By comparison, regeneration in
      mammals is poor and this may reflect a limited dedifferentiation potential of
      mature cells. Because mammalian myotubes can dedifferentiate in the presence of
      newt blastema extract, the present study tested the dedifferentiation induction
      capability of the blastema from the teleost Sternopygus macrurus (SmBE). Our in
      vitro data showed that SmBE did not induce cell cycle reentry of myonuclei in
      myotubes. Instead, SmBE caused myotubes to detach and time-lapse imaging analyses
      characterized the cellular events before their detachment. Furthermore, SmBE
      enhanced myoblast proliferation and reversibly inhibited their differentiation.
      These data suggest the presence of protein factors in SmBE that regulate
      mammalian muscle physiology and differentiation, but do not support the
      conservation of a dedifferentiation induction capability by the blastema of S.
      macrurus.

PMID- 18816864
TI  - Origin and fate of cardiac mesenchyme.
AB  - The development of the embryonic heart is dependent upon the generation and
      incorporation of different mesenchymal subpopulations that derive from intra- and
      extra-cardiac sources, including the endocardium, epicardium, neural crest, and
      second heart field. Each of these populations plays a crucial role in
      cardiovascular development, in particular in the formation of the valvuloseptal
      apparatus. Notwithstanding shared mechanisms by which these cells are generated,
      their fate and function differ profoundly by their originating source. While most
      of our early insights into the origin and fate of the cardiac mesenchyme has come
      from experimental studies in avian model systems, recent advances in transgenic
      mouse technology has enhanced our ability to study these cell populations in the
      mammalian heart. In this article, we will review the current understanding of the
      role of cardiac mesenchyme in cardiac morphogenesis and discuss several new
      paradigms based on recent studies in the mouse.

PMID- 18816866
TI  - Macromolecular dynamic contrast-enhanced (DCE)-MRI detects reduced vascular
      permeability in a prostate cancer bone metastasis model following anti-platelet
      derived growth factor receptor (PDGFR) therapy, indicating a drop in vascular
      endothelial growth factor receptor (VEGFR) activation.
AB  - The antivascular function of the platelet-derived growth factor receptor (PDGFR)
      inhibitor imatinib combined with paclitaxel has been demonstrated by invasive
      immunohistochemistry. The purpose of this study was to 1) noninvasively monitor
      the response to anti-PDGFR treatment, and 2) understand the underlying mechanism
      of this response. Thus, response to treatment was studied in a prostate cancer
      bone metastasis model using macromolecular (biotin-bovine serum albumin [BSA]-Gd
      diethylene triamine pentaacetic acid [GdDTPA]) dynamic contrast-enhanced magnetic
      resonance imaging (DCE-MRI). Human prostate cancer (PC-3MM2) bone metastases that
      caused osteolysis and grew in neighboring muscle showed a high blood-volume
      fraction (fBV) and vascular permeability (PS) at the tumor periphery compared to
      muscle tissue and intraosseous tumor. Imatinib alone or with paclitaxel
      significantly reduced PS by 35% (one-tailed paired t-test, P = 0.045) and 40% (P
      = 0.0003), respectively, whereas paclitaxel alone or no treatment had no effect.
      Based on changes in PS, we hypothesized that imatinib interferes with the
      signaling pathway of vascular endothelial growth factor (VEGF). This mechanism
      was verified by immunohistochemistry. It demonstrated reduced activation of both
      PDGFR-beta and VEGF receptor 2 (VEGFR2) in imatinib-treated mice. Our study
      therefore demonstrates that macromolecular DCE-MRI can be used to detect early
      vascular effects associated with response to therapy targeted to PDGFR, and
      provides insight into the role played by VEGF in anti-PDGFR therapy.

PMID- 18816867
TI  - Investigation of optimizing and translating pH-sensitive pulsed-chemical exchange
      saturation transfer (CEST) imaging to a 3T clinical scanner.
AB  - Chemical exchange saturation transfer (CEST) MRI provides a sensitive detection
      mechanism that allows characterization of dilute labile protons usually
      undetectable by conventional MRI. Particularly, amide proton transfer (APT)
      imaging, a variant of CEST MRI, has been shown capable of detecting ischemic
      acidosis, and may serve as a surrogate metabolic imaging marker. For preclinical
      CEST imaging, continuous-wave (CW) radiofrequency (RF) irradiation is often
      applied so that the steady state CEST contrast can be reached. On clinical
      scanners, however, specific absorption rate (SAR) limit and hardware preclude the
      use of CW irradiation, and instead require an irradiation scheme of repetitive RF
      pulses (pulsed-CEST imaging). In this work, CW- and pulsed-CEST MRI were
      systematically compared using a tissue-like pH phantom on an imager capable of
      both CW and pulsed RF irradiation schemes. The results showed that the maximally
      obtainable pulsed-CEST contrast is approximately 95% of CW-CEST contrast, and
      their optimal RF irradiation powers are equal. Moreover, the pulsed-CEST sequence
      was translated to a 3 Tesla clinical scanner and detected pH contrast from the
      labile creatine amine groups (1.9 ppm). Furthermore, pilot endogenous APT imaging
      of normal human volunteers was demonstrated, warranting future APT MRI of stroke
      patients to elucidate its diagnostic value.

PMID- 18816868
TI  - Practical data acquisition method for human brain tumor amide proton transfer
      (APT) imaging.
AB  - Amide proton transfer (APT) imaging is a type of chemical exchange-dependent
      saturation transfer (CEST) magnetic resonance imaging (MRI) in which amide
      protons of endogenous mobile proteins and peptides in tissue are detected.
      Initial studies have shown promising results for distinguishing tumor from
      surrounding brain in patients, but these data were hampered by magnetic field
      inhomogeneity and a low signal-to-noise ratio (SNR). Here a practical six-offset
      APT data acquisition scheme is presented that, together with a separately
      acquired CEST spectrum, can provide B(0)-inhomogeneity corrected human brain APT
      images of sufficient SNR within a clinically relevant time frame. Data from nine
      brain tumor patients at 3T shows that APT intensities were significantly higher
      in the tumor core, as assigned by gadolinium-enhancement, than in contralateral
      normal-appearing white matter (CNAWM) in patients with high-grade tumors.
      Conversely, APT intensities in tumor were indistinguishable from CNAWM in
      patients with low-grade tumors. In high-grade tumors, regions of increased APT
      extended outside of the core into peripheral zones, indicating the potential of
      this technique for more accurate delineation of the heterogeneous areas of brain
      cancers.

PMID- 18816869
TI  - BOLD imaging in the mouse brain using a turboCRAZED sequence at high magnetic
      fields.
AB  - Functional MRI (fMRI) based on the detection of intermolecular double-quantum
      coherences (iDQC) has previously been shown to provide pronounced activation
      signal. For fMRI in small animals at very high magnetic fields, the essential
      fast gradient echo-based readout methods become problematic. Here, rapid
      intermolecular double-quantum coherence (iDQC) imaging was implemented, combining
      the iDQC preparation sequence with a Turbo spin echo-like readout. Four-step
      phase cycling and a novel intensity-ordered k-space encoding scheme with separate
      acquisition of odd and even echoes were essential to optimize signal to noise
      ratio efficiency. Compared with a single echo readout of iDQC signal,
      acceleration of factor 16 was achieved in phantoms using the novel method at 17.6
      Tesla. In vivo, echo trains consisting of 32 echoes were possible and images of
      the mouse brain were obtained in 30 s. The blood oxygen level dependent (BOLD)
      effect in the mouse brain upon change of breathing gas was observed as average
      signal change of (6.3 +/- 1.1)% in iDQC images. Signal changes in conventional
      multi spin echo images were (4.4 +/- 2.3)% and (8.3 +/- 3.8)% with gradient echo
      methods. Combination of T(2)*-weighting with the fast iDQC sequence may yield
      higher signal changes than with either method alone, and establish fast iDQC
      imaging a robust tool for high field fMRI in small animals.

PMID- 18816870
TI  - Measurement of myocardial frequency offsets during first pass of a gadolinium
      based contrast agent in perfusion studies.
AB  - MRI of myocardial perfusion observed with an extracellular contrast agent has
      proven valuable for the detection of coronary artery disease. During contrast
      enhancement transient dark rim artifacts are sometimes visible, complicating
      diagnosis and quantification. In this work a quantification of the frequency
      offsets caused solely by the first pass of Gd-DTPA in a typical perfusion setup
      was made in vivo and compared with both phantom work and numerical simulations
      data. The results show that numerically simulated and phantom data agree well
      with in vivo frequency offsets. During the first pass main field distortion
      occurs mainly in the subendocardium, and the same pattern is always observed:
      positive for posterior/anterior regions, negative for septal/lateral regions
      (from -69 to 85 Hz). The larger myocardial frequency offsets were measured for
      patients with greater angles between the long axis of the heart and the direction
      of the main field. From these results it would appear that the frequency offsets
      are too weak to cause dark rim artifacts due simply to intravoxel dephasing in a
      typical perfusion sequence. However, when added to other sources of off-resonance
      it can cause dark rims in particular regions of the myocardium wall in balanced
      SSFP sequences.

PMID- 18816871
TI  - Transient MR elastography (t-MRE) using ultrasound radiation force: theory,
      safety, and initial experiments in vitro.
AB  - The purpose of our study was to assess the feasibility of using ultrasound
      radiation force as a safe vibration source for transient MR elastography (t-MRE).
      We present a theoretical framework to predict the phase shift of the complex MRE
      signal, the temperature elevation due to ultrasound, and safety indicators
      (I(SPPA), I(SPTA), MI). Next, we report wave images acquired in porcine liver
      samples in vitro. MR thermometry was used to estimate the temperature elevation
      induced by ultrasound. Finally, we discuss the implications of our results with
      regard to the feasibility of using radiation force for t-MRE in a clinical
      setting, and a specific echo-planar imaging (EPI) MRE sequence is proposed.

PMID- 18816872
TI  - Recent advances in membrane proteomics.

PMID- 18816873
TI  - Exclusion of immortal person-time.

PMID- 18816874
TI  - Extensions to decomposition of the redistributive effect of health care finance.
AB  - The total redistributive effect (RE) of health-care finance has been decomposed
      into vertical, horizontal and reranking effects. The vertical effect has been
      further decomposed into tax rate and tax structure effects. We extend this latter
      decomposition to the horizontal and reranking components of the RE. We also show
      how to measure the vertical, horizontal and reranking effects of each component
      of the redistributive system, allowing analysis of the RE of health-care finance
      in the context of that system. The methods are illustrated with application to
      the RE of health-care financing in Canada.

PMID- 18816875
TI  - A population survey on the use of 24 common medicinal herbs in Australia.
AB  - BACKGROUND: Herbal medicine use is common in Australia but little is known about
      the use of individual herbs. METHODS: A cross-sectional population survey
      conducted in 2007 with a sample of 2526, in the Australian state of Victoria.
      RESULTS: Almost a quarter (22.6%, 95% confidence interval (CI): 20.9-24.2%) of
      survey participants had used at least one medicinal herb in the preceding 12
      months. Aloe vera, garlic and green tea were the most popular, each used by about
      10% of participants. Health enhancement was the most common reason for herbal
      medicine use (69.6% of users) but relatively high proportions of users sought
      relief of specific medical conditions. Over 90% considered their herbal medicine
      to be very or somewhat helpful. Less than half (46.6%) the users were aware that
      there were potential risks associated with herbal medicine. Relatively high
      proportions of female users had taken herbal medicine whilst pregnant (14.4%)
      and/or whilst breast feeding (10.0%). Over half (50.9%) of herbal medicine users
      had also used Western medicine for the same medical condition in the 12-month
      period. Almost the same proportion (49.9%) had used both forms of medication on
      the same day. In deciding whether or not to use herbal medicine, the vast
      majority of survey participants indicated that they would accept the advice of
      their medical practitioner. CONCLUSIONS: In addition to health enhancement,
      specific herbs are commonly used to treat a range of medical conditions, without
      clear evidence of efficacy. Concurrent use of herbal and conventional medicine is
      relatively common and the majority of herbal medicine users are not aware of
      potential adverse effects. It appears that medical practitioners could exert
      significant influence on their patients' decisions about herbal medicine use.

PMID- 18816876
TI  - Use of cyclo-oxygenase 2 inhibitors (COX-2) and prescription non-steroidal anti
      inflammatory drugs (NSAIDS) in UK and USA populations.

PMID- 18816877
TI  - Inmates' possible HIV-exposure claim dismissed.

PMID- 18816878
TI  - Prisoner's HIV, scabies exposure claim survives dismissal.

PMID- 18816879
TI  - Housing. Policy for HIV-positive applicants deemed nondiscriminatory.

PMID- 18816880
TI  - Exposure.  Sentence for criminal transmission of HIV affirmed.

PMID- 18816881
TI  - Which immunizations are safe for HIV patients?

PMID- 18816882
TI  - Rhinoscleroma in a young adult with chronic rhinitis and dyspnea.

PMID- 18816883
TI  - You can lead a horse to water, but you can't make him brush.

PMID- 18816884
TI  - Attitudes regarding vaccination among practitioners of clinical biochemical
      genetics.

PMID- 18816886
TI  - Belgium Royal Academy of Medicine membership list.

PMID- 18816885
TI  - Nutrition and fitness: cultural, genetic and metabolic aspects.

PMID- 18816887
TI  - Bibliography. Current world literature. Cystic fibrosis.

PMID- 18816888
TI  - Curbing rampant cross-contamination and misidentification of cell lines.
AB  - A son's challenge started an emeritus professor of biology on a three-year
      odyssey to get biological researchers to correct a decades-long problem with
      cross-contaminated and misidentified cell lines. These errors may account for
      more than 15% of mammalian cultures, wasting resources and undermining the
      integrity of research.

PMID- 18816889
TI  - [Use of tumor marker CA50].

PMID- 18816891
TI  - [Prioritization of the column space].

PMID- 18816890
TI  - [Ezetimibe=cost effectiveness. Science or a debate contribution from MSD?].

PMID- 18816892
TI  - Inhibition of adenylate cyclase activity in the goldfish melanophore is mediated
      by alpha2-adrenoceptors and a pertussis toxin-sensitive GTP-binding protein.
AB  - The signal-transduction system that mediates the melanosome-aggregating response
      in melanophores of the black-moor goldfish, Carassius auratus, was investigated
      by examining the inhibition of adenylate cyclase activity mediated by alpha
      adrenoceptors in cultured cells. When the melanophores were incubated with 1
      mmol.1-1 3-isobutyl-1-methylxanthine for 5 min, the intracellular level of cyclic
      adenosine-3',5'-monophosphate increased two- to three-fold. Norepinephrine at 100
      nmol. 1-1 and naphazoline at 1 MUmol. 1-1 inhibited the 3-isobutyl-1
      methylxanthine-induced accumulation of cyclic adenosine-3',5'-monophosphate in
      the cells in both the presence and the absence of isoproterenol, a beta
      adrenergic agonist. Methoxamine and phenylephrine also reduced the extent of
      accumulation of cyclic adenosine-3',5'-monophosphate, but only when they were
      present at relatively high concentrations (above 100 MUmol.1-1). The range of
      concentrations at which norepinephrine inhibited the accumulation of cyclic
      adenosine-3',5'-monophosphate was consistent with the range at which it induced
      the aggregation of melanosomes. Pretreatment of the cells with pertussis toxin (1
      MUg.m1-1) for 15 h or treatment with 100 nmol.1-1 yohimbine (an alpha2-adrenergic
      antagonist) inhibited the effects of the alpha-adrenergic agonists on both the
      aggregation of melanosomes and the 3-isobutyl-1-methylxanthine-induced
      accumulation of cyclic adenosine-3',5'-monophosphate, but prazosin (an alpha1
      adrenergic antagonist) at 100 nmol.1-1 was not inhibitory. These results indicate
      that the melanosome-aggregating response of the goldfish melanophore is induced
      mainly via inhibition of the activity of adenylate cyclase,which occurs as a
      result of stimulation of a pathway that involves alpha2-adrenoceptors and a
      inhibitory GTP-binding protein.

PMID- 18816893
TI  - Editorial comments--"West Bank barrier decreases access to schools and health
      services".

PMID- 18816894
TI  - Editorial comments--Disasters, women's health and conservative society: working
      in Pakistan with the Turkish Red Crescent following the earthquake in Southeast
      Asia.

PMID- 18816895
TI  - Editorial comments--Staff procedure skills in management groups during exercises
      in disaster medicine.

PMID- 18816896
TI  - Editorial comment: soft tissue infection after missile injuries to the
      extremities--a non-randomized, prospective study in Gaza City.

PMID- 18816897
TI  - Flexible structure multiple modeling using irregular self-organizing maps neural
      network.
AB  - The MMSOM identification method, which had been presented by the authors, is
      improved to the multiple modeling by the irregular self-organizing map (MMISOM)
      using the irregular SOM (ISOM). Inputs to the neural networks are parameters of
      the instantaneous model computed adaptively at every instant. The neural network
      learns these models. The reference vectors of its output nodes are estimation of
      the parameters of the local models. At every instant, the model with closest
      output to the plant output is selected as the model of the plant. ISOM used in
      this paper is a graph of all the nodes and some of the weighted links between
      them to make a minimum spanning tree graph. It is shown in this paper that it is
      possible to add new models if the number of models is initially less than the
      appropriate one. The MMISOM shows more flexibility to cover the linear model
      space of the plant when the space is concave.

PMID- 18816898
TI  - Editorial comments--"But for the hurricane": measuring natural disaster mortality
      over the long term.

PMID- 18816899
TI  - Re: Beaulieu AD, Peloso PM, Haraoui B, et al. Once-daily, controlled-release
      tramadol and sustained-release diclofenac relieve chronic pain to to
      osteoarthritis: a randomized controlled trial. Pain Res Manage 2008; 13:103-10,
      and Thorne C, Beaulieu AD, Callaghan DJ, et. al. A randomized, double-blind,
      crossover comparison of the efficacy and safety of oral controlled-release
      tramadol and placebo in patients with painful osteoarthritis. Pain Res Manage
      2008; 13:93-102.

PMID- 18816900
TI  - Abstracts of the 19th Ljudevit Jurak International Symposium on Comparative
      Pathology, June 6-7, 2008, Zagreb, Croatia.

PMID- 18816901
TI  - Induction of p27(kip1) by 2,4,3',5'- tetramethoxystilbene is regulated by protein
      phosphatase 2A-dependent Akt dephosphorylation in PC-3 prostate cancer cells.
AB  - trans-Stilbenes induce cytochrome P450 1B1 (CYP1B1) inhibition and cell death.
      2,4,3',5' tetramethoxystilbene (TMS), a synthetic trans-stilbene analog, induced
      apoptotic cell death in PC-3 prostate cancer cells, as evidenced by a decrease in
      the mitochondrial membrane potential. TMS-induced apoptosis was associated with
      an increase in the level of cell cycle inhibitor, p27(kip1), through reduction of
      Akt-mediated Skp2 expression. TMS-induced activation of protein phosphatase 2A
      (PP2A) inhibited Akt phosphorylation and p27(kip1) expression, indicating that
      PP2A is involved in the induction of p27(kip1) via Akt inhibition. These results
      suggest that TMS may inhibit the cell cycle through induction of p27(kip1),
      leading to apoptotic cell death in PC-3 prostate cancer cells.

PMID- 18816902
TI  - The production of care for the elderly.

PMID- 18816903
TI  - Life quality promotion to childhood and adolescence.

PMID- 18816904
TI  - The history of health workers as public policy.

PMID- 18816905
TI  - Poverty, social inequalities and health: challenges for public policies.

PMID- 18816906
TI  - Vacant niches and the possible operation of natural laws in ecosystems.

PMID- 18816907
TI  - Ideal partnerships.

PMID- 18816908
TI  - Now and then: the trouble with students.

PMID- 18816909
TI  - Effectiveness of a tool to improve role negotiation and communication between
      parents and nurses.
AB  - Family-centred care philosophies are promoted by policy makers and nurse leaders,
      although how this ideal is put in practice often remains unclear. Checklists or
      guidelines may be useful tools to assist nurses in determining a parent's desire
      for involvement in their child's care. AIM: To evaluate the effectiveness of a
      documentary tool designed to formalise role negotiation and improve communication
      between parents and nurses. METHODS: A quasi-experimental pre/post-intervention
      study design was used to determine nurses' perceptions of the effectiveness of a
      documentary tool in facilitating nurse-parent discussion about parental desire
      for involvement in the daily care activities of their child while in hospital.
      Nurses in randomly selected wards were assigned to usual practice (control group)
      or the implementation of a Negotiated Care Tool (intervention group) during a
      three-month period. RESULTS: Pre- and post-intervention surveys were completed by
      69 nurses. The tool was associated with attitudinal changes in the desired
      direction for 12 of the 24 nurse responses: nurses in the intervention group were
      significantly more likely to include parents in decision making (p = 0.007);
      encourage parents to ask questions during their child's hospital stay (p =
      0.005); and invite extended family members to participate in care with parental
      permission (p = 0.03). CONCLUSION: The Negotiated Care Tool raised staff
      awareness of the importance of effective communication and negotiation of care
      with parents in busy clinical practice areas. Transparent communication and
      negotiation of roles between nurses and parents are integral to family-centred
      care provision.

PMID- 18816910
TI  - Celebrating child health nursing.

PMID- 18816911
TI  - How to make good children's nurses: children's view.
AB  - A consultation was held to seek children's views on how to make better children's
      nurses to influence a new curriculum. In one-to-one sessions, ten hospitalised
      children were asked to complete body outlines of 'good' and 'not so good' nurses.
      Based on this the children were asked about how good children's nurses could be
      made. They agreed that although children's nurses are special people with some
      innate characteristics, they also needed education to make them good at nursing
      children. The children were able to identify three areas of learning that could
      help to make a good children's nurse. The researchers categorised these as:
      attitudinal and professional persona; Cognitive and psychomotor learning;
      experiential learning. The consultation highlighted methodological issues in
      consulting children about curriculum development, as well as drawing our
      attention to how children are represented in the children's nursing curriculum.
      Child nurse lecturers should work in collaboration with clinical colleagues and,
      more importantly, children to develop teaching and learning in children's
      nursing.

PMID- 18816912
TI  - Why did you do it like that? Examining clinical decisions.
AB  - Clinical decisions are often informed by the experience and expertise of
      colleagues but this may not be enough to ensure safe, effective practice. Two
      decisions made about the care of an infant in a special care baby unit are
      analysed to demonstrate the importance of basing decisions, not just on
      experience, but also on published research as well as protocols, guidelines and
      textbooks that are informed by research. A seven-stage model of decision making
      is used as a framework to support the analysis, which identifies the importance
      of cognitive skills such as generating and testing hypotheses in the process of
      making effective decisions.

PMID- 18816913
TI  - Asthma guideline update.

PMID- 18816914
TI  - Chastising a child--the legal position.
AB  - Chastisement of children can take many forms, some of which could be offences
      under law. If the child was afraid of a physical attack because the parent was
      shouting at them, this could constitute an assault. A parent or other adult could
      face a charge of battery for physically striking a child. Under English law,
      reasonable chastisement is a defence available to a parent who may face legal
      prosecution for the action they take against their child. This article reviews
      the nature of chastisement and the current legal situation using relevant cases
      and related legislation. At present, a parent is entitled under English law to
      chastise their child; this includes smacking them where doing so leaves no mark
      on the child.

PMID- 18816915
TI  - Benchmarks for children's orthopaedic nursing.
AB  - Variability in practice and quality of care for children and young people with
      orthopaedic conditions was identified by a network of nurses working in this
      specialty. Nine benchmarks were developed to help address this variability by
      providing support for nurses to evaluate and improve practice where necessary.
      The process of developing the benchmarks is described and lessons learnt are
      discussed, including the challenges for experts of making the nature of their
      work explicit. Following publication and dissemination of the benchmarks, an
      evaluation of their usefulness is planned.

PMID- 18816916
TI  - Sampling in quantitative research.

PMID- 18816917
TI  - A feasibility study of an educational intervention for children with daytime
      wetting.
AB  - Daytime wetting in children is a common problem and though behavioural and
      educational interventions have been recommended, they have not been extensively
      evaluated. AIM: To evaluate the feasibility and usefulness of an educational
      intervention (home workbook) for daytime wetting in children aged six to ten
      years. METHODS: The workbook was piloted with two groups of children with daytime
      wetting. One group (n = 10) received verbal information only, while the other
      group (n = 10) received the same verbal information and the workbook supporting
      the verbal information. Telephone surveys were undertaken every two weeks to
      monitor the child's progress. RESULTS: The workbook was acceptable and usable by
      both children and parents, and was positively evaluated. Though the results do
      not show a clinically meaningful improvement in symptoms, they suggest a larger
      trial is worthwhile. CONCLUSION: A simple, paper-based educational intervention
      for children and parents on the management of daytime wetting is acceptable and
      usable.

PMID- 18816918
TI  - Day case surgery admission packs.

PMID- 18816919
TI  - Look out doctor, you may be getting framed: heuristics in medical decision
      making.

PMID- 18816920
TI  - Metabolic demands of body armor on physical performance in simulated conditions.
AB  - The purpose of this study was to examine physical work performance, energy cost,
      and physiological fatigue in military personnel during simulated operational
      conditions. Using a within-subject, repeated-measures design, 34 military
      personnel volunteered to undergo two experimental conditions: with body armor
      (BA+) and without BA (BA-). Subjects walked on a treadmill for 30 minutes and
      completed a physical performance battery during each of two sessions, which were
      separated by > or = 5 days. Subjects with BA+ as compared with BA- had
      significantly greater increases in: oxygen uptake (VO2) at slow (16.8 +/- 1.5 vs.
      18.8 +/- 1.7 mL x kg(-1) x min(-1)) and moderate paces (34.8 +/- 3.9 vs. 40.8 +/-
      5.0 mL x kg(-1) x min(-1)); blood lactate at a moderate pace (4.0 +/- 2.4 vs. 6.7
      +/- 2.6 mmol/L); heart rate at slow (107 +/- 14 vs. 118 +/- 16 beats per minute)
      and moderate paces (164 +/- 16 vs. 180 +/- 13 beats per minute); and ratings of
      perceived physical exertion at slow (8.4 +/- 1.5 vs. 10.4 +/- 1.8) and moderate
      paces (14.3 +/- 2.3 vs. 16.7 +/- 2.1). Physical tasks were significantly affected
      by BA: under BA+, men performed 61% fewer pull-ups and women's hang time was
      reduced by 63%; stair stepping was reduced by 16% for both men and women. BA
      significantly impacted the physical work capacity of militarily relevant tasks.
      Specifically, wearing BA significantly increased VO2 when walking at both slow
      and moderate paces. The potential for physical exhaustion is high and performance
      of physical tasks is markedly impaired when wearing BA.

PMID- 18816921
TI  - U.S. Army disease and nonbattle injury model, refined in Afghanistan and Iraq.
AB  - Previous analysis of Operation Desert Shield/Operation Desert Storm data yielded
      a disease and nonbattle injury (DNBI) model using distinct 95th percentile daily
      admission rates during the three phases of a war-fighting operation to predict
      medical requirements. This study refines the model with data from Operation
      Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF). Inpatient health care
      records of U.S. Army soldiers deployed to OEF and OIF who were admitted with DNBI
      diagnoses were analyzed. DNBI admission rates for OEF and OIF were compared with
      rates for Operation Desert Shield/Operation Desert Storm. DNBI admission rates
      for OEF and OIF were lower than those for Operation Desert Shield/Operation
      Desert Storm. Rates among the phases of OIF were distinctly different. DNBI
      admission rates have been reduced during recent deployments. The concepts of the
      original model based on Operation Desert Shield/Operation Desert Storm data were
      validated by experiences during OEF and OIF. Continuous surveillance of DNBI
      admission rates is recommended.

PMID- 18816922
TI  - Reference data from the automated Neuropsychological Assessment Metrics for use
      in traumatic brain injury in an active duty military sample.
AB  - The current study examined the performance of active duty soldiers on the
      Automated Neuropsychological Assessment Metrics (ANAM) traumatic brain injury
      test battery, to expand the reference data for use in military settings. The
      effects of age and gender on cognitive performance also were explored. The ANAM
      traumatic brain injury battery, consisting of six performance tests and two
      subjective scales, was administered to a sample of healthy active duty soldiers
      (N = 5,247) as part of a concussion surveillance program. Performance means and
      SDs, stratified according to age and gender, are reported as reference data. In
      addition, the impact of age and gender on performance measures was analyzed.
      Because ANAM is rapidly being adopted for use in many military medical and
      research applications, the establishment of these reference values is invaluable,
      particularly for assisting with rapid accurate evaluation and treatment in
      clinical settings.

PMID- 18816923
TI  - Acceptability of adverse childhood experiences questions for health surveillance
      in U.S. Armed Forces.
AB  - BACKGROUND: Research has documented a consistent and strong association between
      adverse childhood experiences (ACE) and negative health outcomes in adulthood.
      The Department of Defense is expanding health surveillance of military members
      and considering the inclusion of ACE questions. OBJECTIVE: To explore the
      perceptions and attitudes of service members and spouses regarding the use of ACE
      questions in routine health surveillance. METHOD: Forty-one active duty service
      members and spouses were interviewed at two Army troop medical centers.
      Semistructured qualitative interviews were used to examine their views regarding
      the use of ACE questions in military health surveillance. RESULTS: Participants
      believe there is value in health surveillance; however, they are cautious about
      providing ACE or other information that may be perceived negatively, without
      confidentiality reassurances. CONCLUSION: Successful employment of ACE questions
      in active duty military health surveillance will depend on the ability of
      military health officials to ensure confidentiality and to communicate the
      relevance of ACE to health status.

PMID- 18816924
TI  - Establishing and maintaining a volunteer victim advocate program to assist
      victims of domestic violence in the U.S. Army.
AB  - A descriptive evaluation of a volunteer victim advocacy (VA) program was
      conducted to assist domestic violence victims on the scene of a domestic violence
      incident on a 24-hour per day basis at a U.S. Army installation. A total of 87
      volunteers contributed data to this evaluation. The VAs conducted on-the-spot
      client safety planning using risk factor assessment. Additional information was
      given to the client about post programs and services. VAs were evaluated and
      monitored through initial, periodic, and exit interviews. They were asked about
      their training needs, the most difficult situations they confronted, what they
      did best, and whether the VA program met their personal needs. While the Army
      supports victim advocacy by regulation, it often does not provide sufficient
      funds to support the hiring of the necessary staff. Hence, a volunteer program
      may be the only feasible approach to provide advocacy assistance for abused
      spouses in the Army above a minimum level. Drawing on the services of trained
      volunteers allowed the Family Advocacy Program at this installation to accomplish
      its mandated mission. Suggestions for further research in VA programs are
      presented.

PMID- 18816925
TI  - Characteristics of domestic violence incidents reported at the scene by volunteer
      victim advocates.
AB  - At a single U.S. Army installation from 1997 to 2005, domestic violence volunteer
      victim advocates assisted 1,417 clients in 1,380 physical and 301 verbal abuse
      incidents. The average soldier and spouse population during this time was
      slightly less than 10,000. Advocates went to the scene of the incident to talk to
      the victim to ensure that her/his rights were observed, to determine whether the
      victim was safe, was referred to the hospital social work service for assessment,
      and had the information necessary to negotiate the complex military and community
      systems. The advocate inquired of the victim the characteristics of the incident
      and risk factors in the history of the relationship. In many incidents, risk
      factors indicated a history of serious violence by the offender including an
      increasing level of violence, stalking, and assaults. Frequently reported
      precipitants of incidents were relationship problems, jealously, and infidelity.
      Spouses often reported previous attempts to leave and to get help. Advocates play
      an important role in gathering information uniquely available at the scene that
      can be useful in planning education and intervention programs to reduce domestic
      violence in the Army, the military services, and civilian society.

PMID- 18816926
TI  - Referrals for alcohol use problems in an overseas military environment:
      description of the client population and reasons for referral.
AB  - Being stationed in an overseas installation has been associated with increased
      risk for alcohol use problems. Okinawa is a unique overseas environment that
      often challenges service members with separation from family and friends, limited
      resources and recreational activities, a high rate of deployment, and restrictive
      local laws. Single, young, male services members in the junior ranks are at
      increased risk for poor coping, particularly relying on alcohol use. Maladaptive
      alcohol use places them at increased risk for engaging in illegal behavior and
      other negative consequences that subsequently lead them to be referred for an
      evaluation for alcohol use problems. Alcohol use problems negatively affect
      health, safety, morale, and mission readiness. Findings from this study strongly
      suggest that prevention and wellness programs should target young service members
      in the junior ranks for training on responsible alcohol use, alcohol use
      problems, and basic coping for improved impact on health and mission readiness.

PMID- 18816927
TI  - The relation between good communication skills on the part of the physician and
      patient satisfaction in a military setting.
AB  - OBJECTIVE: The objective of this study was to assess the correlation between
      patients' view of the consultation and the assessment of an auditing physician on
      the same consultation. METHODS: A prospective study in military clinics was
      conducted. A board-certified family physician made a real-time semistructured
      assessment of the medical consultation. At the end of it, the patient was asked
      to fill in the Consultation Satisfaction Questionnaire. The degree of correlation
      between patients' satisfaction from consultation and the scores given by the
      auditing physician was evaluated. RESULTS: Twelve primary care physicians were
      evaluated. A total of 117 (76.5%) of 153 patients returned their questionnaires.
      A positive correlation was found between physician's communication skills and
      general satisfaction (r = 0.614), professional care (r = 0.367), and depth of
      relationship (r = 0.275) calculated from the Consultation Satisfaction
      Questionnaire. No correlation was found between patient satisfaction and other
      consultation skills. CONCLUSIONS: Good communication skills may enhance patient
      satisfaction. It may be advisable to investigate whether a training program to
      enhance the physician's communication skills can improve patient satisfaction.

PMID- 18816928
TI  - Evaluation of dermatologic conditions by primary care providers in deployed
      military settings.
AB  - Dermatologic illnesses have historically been a significant source of morbidity
      and resource utilization in fielded military forces. The impact of cutaneous
      diseases during U.S. military conflicts is reviewed, and recent data from Craig
      Joint Theater Hospital at Bagram Air Field in Afghanistan are presented,
      confirming previous experience. A discussion of the difficulties of diagnosing
      and treating dermatologic conditions for deployed primary care providers is
      provided, including recommendations to improve patient care and military unit
      readiness.

PMID- 18816929
TI  - Changes in maximum muscle strength and rapid muscle force characteristics after
      long-term special support and reconnaissance missions: a preliminary report.
AB  - PURPOSE: The purpose of the present study was to examine the impact of 8 days of
      immobilization during a Special Support and Reconnaissance mission (SSR) on
      muscle mass, contraction dynamics, maximum jump height/power, and body
      composition. METHODS: Unilateral maximal voluntary contraction, rate of force
      development, and maximal jump height were tested to assess muscle strength/power
      along with whole-body impedance analysis before and after SSR. RESULTS: Body
      weight, fat-free mass, and total body water decreased (4-5%) after SSR, along
      with impairments in maximal jump height (-8%) and knee extensor maximal voluntary
      contraction (-10%). Furthermore, rate of force development was severely affected
      (-15-30%). CONCLUSIONS: Eight days of immobilization during a covert SSR mission
      by Special Forces soldiers led to substantial decrements in maximal muscle force
      and especially in rapid muscle force capacity. This may negatively influence the
      ability for rapid exfiltration and redeployment, respectively.

PMID- 18816930
TI  - Federally employed physician assistants.
AB  - The federal government is the largest single employer of clinically active
      physician assistants (PAs) in the United States, with > 3,000 PAs in 2008. PAs
      are present within the Departments of Defense, Veterans Affairs, Health and Human
      Services, Justice, and Homeland Security. Most are civil servants or hold a
      commission in the uniformed services. Most employing agencies have expanding
      needs for PAs. This overview presents a framework of how PAs are being used and
      the critical roles they play in the federal health care system. Because civilian
      job opportunities for PAs are plentiful, the federal system is seeking strategies
      for recruitment and retention. A centralized plan may be one useful
      recommendation.

PMID- 18816931
TI  - Health indicators in children from Meulaboh, Indonesia, following the tsunami of
      December 26, 2004.
AB  - The French Army medical service carried out an epidemiological survey to estimate
      health indicators in children living in Meulaboh, Indonesia, in the weeks
      following the tsunami of December 26, 2004, within a sample from refugee camps,
      schools, and quarters of the town. Thirty-four percent of the children in camps,
      21.9% in schools, and 49.5% from quarters presented psychological trauma.
      Malnutrition affected 20.5% in camps and 34.4% in the town between 6 and 59
      months, 11.3% in camps, and 7.6% in schools between 6 and 15 years. The children
      had suffered various symptoms since the tsunami; access to care was possible for
      53.9% in the camps, 23.8% from schools, and 39.3% from the town. Those results
      have been subsequently used by the local health authorities to improve child
      health care. The method used for this survey could be applied for future disaster
      scenarios.

PMID- 18816932
TI  - Military and leisure-time noise exposure and hearing thresholds of Finnish
      conscripts.
AB  - This study presents an evaluation of the total cumulative noise exposure of
      Finnish conscripts (N = 416) during military service. All of the conscripts
      underwent a hearing screening and filled out a noise exposure questionnaire at
      the beginning and end of their military service. Eighty-nine percent of the
      conscripts were exposed weekly to military noise of over 85 dBA during the
      service. Eighteen percent of the conscripts had already reached at the end of
      their military service a cumulative noise dose corresponding to noise exposure of
      85 dB for 40 years. During military service, permanent hearing loss of > 20 dB in
      the frequency range of 0.5 to 8 kHz increased from 19 to 27% among the
      conscripts.

PMID- 18816933
TI  - Distribution of ametropia among military beneficiaries.
AB  - In addition to active duty military members and their dependents, retired
      military members and the members of their immediate families are eligible for eye
      care in military medical treatment facilities. We recorded refractive errors,
      age, sex, and race for 4,595 individual beneficiaries visiting optometry clinics
      at two U.S. Air Force medical treatment facilities during 2005 to 2006.
      Evaluation revealed most patients requiring optical correction were myopic, or
      near-sighted, and there was an increase in the degree of myopia between ages 4
      and 23. That trend is reversed at age 30 and, by age 60, most patients are
      hyperopic, or far-sighted. Both trends were true for both sexes and all
      ethnicities studied. The degree of astigmatism was distributed similarly between
      races and age groups. Presbyopia occurred at similar ages and progressed at
      similar rates in all ethnicities and both sexes.

PMID- 18816934
TI  - ON-Q anesthetic pump in gynecologic oncology: feasibility study of a novel
      placement technique at an army hospital.
AB  - OBJECTIVES: The goals were (1) to describe a novel placement technique for the ON
      Q anesthetic system based on somatic neural anatomy and (2) to determine its
      feasibility, efficacy, and associated morbidity among surgical patients on a
      gynecologic oncology service. METHODS: A retrospective observational study of 100
      consecutive patients who underwent a vertical laparotomy and received an ON-Q
      system was performed. The ON-Q system was composed of a soaker catheter (threaded
      longitudinally within the rectus sheaths) and an elastomer pump that infused 0.5%
      bupivacaine at 2 mL/hour for up to 5 days. RESULTS: The average duration of ON-Q
      system use was 4.4 days (range, 2-5 days). The median numeric pain scores (range,
      0-10) were 3, 2, 1, 0, and 0 on postoperative days 1, 2, 3, 4, and 5,
      respectively. Complications encountered included suturing of the catheter to the
      fascia (n = 1), wound hematomas (n = 2), and device failure (n = 1). CONCLUSIONS:
      Intrafascial placement of the ON-Q soaker catheter for bupivacaine infusion
      appears effective for incisional analgesia, with negligible wound morbidity and
      device failure rates.

PMID- 18816935
TI  - Interlaminar discectomy in lumbar disc herniation: shorten postoperative return
      to work period in recruits undergoing military training.
AB  - The operative treatment of lumbar disc disease has long challenged spine
      surgeons. In this study, we aimed to show that recruits with lumbar disc
      herniation managed by the interlaminar approach could return to work after 6
      weeks. Forty male recruits were included in this study and interlaminar
      discectomy was adequate in 40 cases. Early postoperative rehabilitation had a
      positive effect on early return to work. We believe that interlaminar lumbar
      discectomy is an effective technique for treating patients with herniated lumbar
      discs; with early postoperative rehabilitation, recruits can return to work 6
      weeks after surgery.

PMID- 18816936
TI  - Successful treatment of vancomycin-resistant enterococcal ventriculitis in a
      pediatric patient with linezolid.
AB  - Although vancomycin-resistant Enterococcus infection of the central nervous
      system is not common, this organism is becoming an increasing problem in
      nosocomial infections. We report a 17-month-old male infant with an externalized
      ventricular peritoneal shunt secondary to infection who subsequently developed a
      vancomycin-resistant Enterococcus faecium ventriculitis. This infection was
      successfully treated with a 28-day course of linezolid while monitoring linezolid
      drug levels in both the cerebral spinal fluid and serum. This case supports the
      use of linezolid in treating such resistant infections. However, our drug level
      results suggest that further investigation is needed to determine the optimal
      dosing of linezolid in treatment of central nervous system infection in pediatric
      patients.

PMID- 18816937
TI  - Polyp inside the concha bullosa: unusual manifestation of chronic rhinosinusitis.
AB  - Chronic rhinosinusitis has complex pathophysiological features. The role of
      anatomic variations in the development of sinusitis remains unclear. We describe
      a rare manifestation of this disease, a polyp inside the pneumatized concha
      polyposa. A 23-year-old male patient had been suffering from headache, nasal
      obstruction, loss of the sense of smell, and postnasal discharge. Computed
      tomographic scans of the sinuses showed bilateral conchae bullosae, with a polyp
      inside the left one. Therapy included endoscopic nasal surgery and postoperative
      topical corticosteroid and macrolide treatment. We discuss the influence of
      sinusitis on the phenomenon of "sinus headache." We also comment on the use of
      topical corticosteroids and macrolides in preoperative and postoperative
      treatment of chronic rhinosinusitis with nasal polyposis.

PMID- 18816938
TI  - Severe epistaxis from an intracranial vascular bleed from grenade injury.

PMID- 18816939
TI  - Are parental concerns about children's inactivity warranted, and are they
      associated with a supportive home environment?
AB  - This paper explores parental concern about children's activity levels and whether
      parents who are concerned about their child's activity provide a supportive
      environment. A sample of 615 parents of 5-6-year-old children and 947 parents of
      10-12-year-old children completed a questionnaire. Just over 50% of parents
      reported they were concerned their child was not getting enough activity.
      Children of concerned parents were less active than those whose parents were not
      concerned. These findings suggest that parents who are concerned about their
      child's physical activity levels provided a less supportive environment for
      physical activity than parents who are not concerned. The challenge for public
      health will be to harness parental concerns and translate them into action.

PMID- 18816940
TI  - Psychometric evaluation of the exercise identity scale among Greek adults and
      cross-cultural validity.
AB  - The present study reported on translating the Exercise Identity Scale (EIS:
      Anderson & Cychosz, 1994) into Greek and examining its psychometric properties
      and cross-cultural validity based on U.S. individuals' EIS responses. Using four
      samples comprising 33, 103, and 647 Greek individuals, including exercisers and
      nonexercisers, and a similar sample comprising 800 U.S. individuals, the
      concurrent validity, factor structure, internal reliability, test-retest
      reliability, external validity, gender invariance, and cross-cultural validity of
      the EIS responses were examined using confirmatory factor analytical procedures.
      The results supported the concurrent validity, an adequate unidimensional factor
      structure for the translated EIS and the internal reliability and test-retest
      reliability over a 6-week interval. Further, cross-gender configural, partial
      metric, partial strong factorial, and partial strict factorial invariance and
      cross-cultural configural and partial metric invariance supported the cross
      cultural equivalence of the EIS versions. Moreover, the external validity of the
      translated EIS responses was also supported. Overall, the findings supported the
      validity of the exercise identity construct outside North American boundaries and
      the EIS items' equivalence, providing initial evidence for its cross-cultural
      applicability.

PMID- 18816941
TI  - A confirmatory study of rating scale category effectiveness for the Coaching
      Efficacy Scale.
AB  - This study extended validity evidence for measures of coaching efficacy derived
      from the Coaching Efficacy Scale (CES) by testing the rating scale
      categorizations suggested in previous research. Previous research provided
      evidence for the effectiveness of a four-category (4-CAT) structure for high
      school and collegiate sports coaches; it also suggested that a five-category (5
      CAT) structure may be effective for youth sports coaches, because they may be
      more likely to endorse categories on the lower end of the scale. Coaches of youth
      sports (N = 492) responded to the CES items with a 5-CAT structure. Across rating
      scale category effectiveness guidelines, 32 of 34 evidences (94%) provided
      support for this structure. Data were condensed to a 4-CAT structure by
      collapsing responses in Category 1 (CAT-1) and Category 2 (CAT-2). Across rating
      scale category effectiveness guidelines, 25 of 26 evidences (96%) provided
      support for this structure. Findings provided confirmatory, cross-validation
      evidence for both the 5-CAT and 4-CAT structures. For empirical, theoretical, and
      practical reasons, the authors concluded that the 4-CAT structure was preferable
      to the 5-CAT when CES items are used to measure coaching efficacy. This
      conclusion is based on the findings of this confirmatory study and the more
      exploratory findings of Myers, Wolfe, and Feltz (2005).

PMID- 18816942
TI  - Memory drum theory's C movement: revelations from Franklin Henry.
AB  - Franklin Henry's "memory drum" theory of neuromotor reaction (Henry & Rogers,
      1960) was one of the most influential studies of the response programming stage
      of information processing. The paper is the most-cited study ever published in
      the Research Quarterly for Exercise and Sport. However, few people know there is
      a noteworthy error in the paper, namely in the description of the C movement, the
      most complicated of the three responses studied. Henry himself was unaware of the
      error for nearly 20 years after the paper's publication. The purpose of our paper
      is to accord the factual record its due respect by revealing the history about
      the error and its correction. The data are in the form of the original 1960 paper
      which describes the C movement, a paper by Howell (1953), and personal letters
      from Henry dating from 1979, when the error was first discovered, and continuing
      through 1986. In one letter, Henry attributed the error to a mild and specific
      form of aphasia, manifested by word reversals, from which he suffered throughout
      his scholarly life. Such a revelation makes the career of this remarkable scholar
      even more remarkable.

PMID- 18816943
TI  - Attentional focus effects in balance acrobats.
AB  - Performing and learning motor skills has been shown to be enhanced if the
      performer adopts an external relative to internal focus (or no focus) of
      attention (Wulf 2007). The present study examined the generalizability of this
      effect to top-level performers (balance acrobats). Participants performed a
      balance task (standing on an inflated rubber dish) under each of three
      attentional focus conditions: (a) external focus (i.e., minimize movements of the
      disk), (b) internal focus (i.e., minimize movements of the feet), and (c) control
      conditions (no focus instructions). While there were no differences between
      conditions in the amount of postural sway, the frequency of movement adjustments
      was higher in the control condition, relative to both external and internal focus
      conditions. This suggests that movement automaticity and postural stability were
      greatest when the balance experts were free to adopt their "normal" focus of
      attention. The finding implies that there may be a limit to the performance
      enhancing effects of external focus instructions for top-level performers. The
      findings are discussed in terms of action control levels and possible changes in
      the optimal attentional focus with the performer's level of expertise.

PMID- 18816944
TI  - Are preschool children active enough? Objectively measured physical activity
      levels.
AB  - The present study aimed to describe accelerometer-based physical activity levels
      in 4- and 5-year-old children (N = 76) on 2 weekdays and 2 weekend days. The
      children were sedentary for 9.6 hr (85%) daily, while they engaged in moderate to
      vigorous physical activity (MVPA) for 34 min (5%). Only 7% of the children
      engaged in MVPA for 60 min per day, and only 26% reached the standard of 120 min
      of total activity. Their engagement in MVPA did not significantly differ between
      weekend and weekdays. Mean activity counts and minutes in MVPA did not differ
      between genders. Physical activity levels in this sample of preschool children
      were far lower than recommended.

PMID- 18816945
TI  - The influence of domain specificity on motivation in physical education.
AB  - With the assumption that domain specificity would significantly influence
      students' motivation, our study was designed to investigate between- and within
      domain relations of task value, perceived autonomy and competence, and
      achievement goal orientations across physical education and mathematics. Urban
      adolescents (N = 273, ages 12-14 years) completed questionnaires assessing these
      motivational constructs in both subjects. Based on our confirmatory factor
      analyses and fit indexes, all motivational constructs demonstrated strong subject
      specificity. Strengths of associations between physical education and mathematics
      differed by individual motivational constructs. Within-domain interrelations of
      these constructs were not consistent across physical education and mathematics.
      Our findings suggest that domain specificity in physical education plays a
      significant role in students' motivation.

PMID- 18816946
TI  - Children's experiences of fun and enjoyment during a season of sport education.
AB  - This paper reports on a 16-week sport education (SE) unit with just over 70 year
      5 students (M age = 10.04 years) in one United Kingdom school during the spring
      and summer terms and discusses students' SE experiences. Student interviews were
      conducted throughout the season and a questionnaire on different motivation
      aspects was administered prior to and before completing the SE season. We report
      and examine the data in relation to hypothesized influences on fun and enjoyment,
      including being part of a team, autonomy, and improving game play. The principal
      reasons SE may be more enjoyable than previous physical education lessons include
      the greater opportunities for autonomy, affiliation, and competition, plus
      perceived learning.

PMID- 18816947
TI  - Cardiovascular fitness in obese versus nonobese 8-11-year-old boys and girls.
AB  - The purpose of this study was to compare cardiovascular fitness between obese and
      nonobese children. Based on body mass index, 118 were classified as obese (boys
      [OB] = 62, girls [OG] = 56), while 421 were nonobese (boys [NOB] = 196, girls
      [NOG] = 225). Cardiovascular fitness was determined by a 1-mile [1.6 km] run/walk
      (MRW) and estimated peak oxygen uptake (VO2peak) and analyzed using two-way
      analyses of variance (Gender x Obese/Nonobese). MRW times were significantly
      faster (p < .05) for the NOB (10 min 34 s) compared to the OB (13 min 8 s) and
      the NOG (13 min 15 s.) compared to the OG (14 min 44 s.). Predicted VO2peak
      values (mL x kg(-1) x min(-1)) were significantly higher (p < .05) for the NOB
      (48.29) compared to the OB (41.56) and the NOG (45.99) compared to the OG
      (42.13). MRW was compared between obese and nonobese participants on the
      President's Challenge (2005), the National Children and Youth Fitness Study, and
      FITNESSGRAM HFZ standards. The nonobese boys and girls scored higher on all
      three, exhibiting better cardiovascular fitness as compared to obese
      counterparts.

PMID- 18816948
TI  - Basic psychological skills usage and competitive anxiety responses: perceived
      underlying mechanisms.
AB  - This study examined the relationship between basic psychological skills usage
      (i.e., goal-setting, imagery, self-talk, and relaxation) and the intensity and
      directional dimensions of competitive anxiety. Semistructured interviews were
      used on a sample of 15 elite athletes (M age = 24.3 years, SD = 4.2) from a
      variety of team and individual sports. Findings revealed that the participants
      maintained the intensity of their anxiety response prior to competition and could
      deploy goal-setting, imagery, or self-talk to enable facilitative interpretations
      of anxiety-related symptoms to performance. Higher levels of self-confidence and
      an optimistic outlook toward forthcoming competition were also expressed. The
      underlying mechanisms perceived to be responsible for these effects included
      effort and motivation, attentional focus, and perceived control over the anxiety
      response.

PMID- 18816949
TI  - Explaining long-term exercise adherence in women who complete a structured
      exercise program.
AB  - The purpose of this study was to qualitatively examine factors related to
      physical activity adherence to understand why women continue to participate in
      long-term exercise after completing a structured exercise program. Data were
      collected from focus groups, interviews, and e-mails, and analysis used grounded
      theory. The central category related to physical activity adherence was self
      worth. Motivation, activity enjoyment, priorities, body image, ability to access
      support, and self-regulation skills had an impact on the self-worth of
      nonadherers and adherers. Women must value themselves enough to continue to
      participate in physical activity once they start. Exercise and fitness
      professionals are encouraged to use strategies to increase self-worth and long
      term adherence to physical activity. Some recommended strategies include (a)
      increasing motivation and enjoyment relative to activity, (b) making activity a
      high priority in a woman's life, (c) improving or deemphasizing body image, (d)
      increasing a woman's ability to access support, and (e) facilitating the use of
      self-regulation strategies. This study is the first to examine qualitative
      perspectives of exercise adherence among women who completed a structured
      exercise program. Several concepts related to adherence presented in the
      quantitative literature are confirmed and enhanced in this study.

PMID- 18816950
TI  - Beating the bunker: the effect of PETTLEP imagery on golf bunker shot
      performance.
AB  - The aim of this study was to compare the effects of physical practice with
      PETTLEP-based (Physical, Environment, Task, Timing, Learning, Emotion and
      Perspective; Holmes & Collins, 2001) imagery and PETTLEP + physical practice
      interventions on golf bunker shot performance. Thirty-two male county- or
      international-level golfers were assigned to one of four groups; PETTLEP imagery,
      physical practice, PETTLEP + physical practice, or control. The PETTLEP imagery
      group imaged 15 bunker shots, their interventions incorporating PETTLEP
      components, such as physical, environment, and emotion, twice a week. The
      physical practice group physically performed their 15 bunker shots twice per
      week; the PETTLEP + physical practice group performed PETTLEP imagery once per
      week and physical practice once per week. Each group performed their respective
      tasks for 6 weeks. Pre- and posttests consisted of 15 bunker shots, with points
      awarded according to the ball proximity to the pin. All groups improved
      significantly (p < .01) from pre- to posttest, and the PETTLEP + physical
      practice group improved more (p < .05) than the PETTLEP and physical practice
      groups. However, there was no significant difference between the physical
      practice and PETTLEP groups (p > .05). Findings, therefore, support the
      effectiveness of PETTLEP in enhancing golf performance, especially when combined
      with physical practice.

PMID- 18816951
TI  - How do expert soccer players encode visual information to make decisions in
      simulated game situations?
AB  - The aim of this study was to determine what visual information expert soccer
      players encode when they are asked to make a decision. We used a repetition
      priming paradigm to test the hypothesis that experts encode a soccer pattern's
      structure independently of the players' physical characteristics (i.e., posture
      and morphology). The participants were given either realistic (digital photos) or
      abstract (three-dimensional schematic representations) soccer game patterns. The
      results showed that the experts benefited from priming effects regardless of how
      abstract the stimuli were. This suggests that an abstract representation of a
      realistic pattern (i.e., one that does not include visual information related to
      the players'physical characteristics) is sufficient to activate experts'specific
      knowledge during decision making. These results seem to show that expert soccer
      players encode and store abstract representations of visual patterns in memory.

PMID- 18816952
TI  - Gaze behavior in basketball shooting: further evidence for online visual control.

PMID- 18816953
TI  - Learning benefits of self-controlled knowledge of results in 10-year-old
      children.

PMID- 18816954
TI  - Puberty and physical self-perceptions of competitive female figure skaters II:
      maturational timing, skating context, and ability status.

PMID- 18816955
TI  - Relationship of social physique anxiety to indicators of physique.

PMID- 18816956
TI  - Physical Activity Enjoyment Scale short form--does it fit for children?

PMID- 18816957
TI  - Domain specificity,task specificity, and expert performance.

PMID- 18816958
TI  - Physician executive job market appears strong.

PMID- 18816959
TI  - Do you need that second degree?

PMID- 18816960
TI  - NASA doc treats patients out of this world.

PMID- 18816961
TI  - The expanding roles of the chief medical officer.

PMID- 18816962
TI  - Adopting the CEO model--why physician executives should not be required to
      practice medicine.

PMID- 18816963
TI  - Wake-up call leads to organizational transformation.
AB  - We've all heard the buzzwords--organizational transformation, corporate
      compliance, culture change, transparency. We may tire of the jargon, but as
      pressure continues to mount, organizations--particularly those viewed as
      performing public service--are being forced to rethink old habits, find truly
      measurable ways to evaluate performance, and become more accountable in every
      aspect of their operations.

PMID- 18816964
TI  - Physician leader, be careful not to let arrogance stand in for competence.
AB  - At various points in your physician leadership career you may feel such a sense
      of mastery that you delude yourself into believing that you are better than you
      are. Depending on the size of your ego, that time may come sooner or later than
      in your peers, but, be mindful, it could come.

PMID- 18816965
TI  - Customer satisfaction in health care--time for transparency.

PMID- 18816966
TI  - A new tool for hospital/ physician strategic alignment: the subsidiary physician
      corporation.
AB  - Physicians' and hospitals' strategies often diverge--with poor results for both.
      The causes of this divergence are many. They include different methods of
      payment, divisive governmental regulations (like Stark) and cultural differences.

PMID- 18816967
TI  - Retrospective audits: facing the black white problems of a gray process.

PMID- 18816968
TI  - Medical malpractice: preparing for trial.
AB  - In the last column (The Physician Executive, 34(3), May/June 2008) I discussed
      the intricacies of your deposition. Assuming that both parties still feel their
      cases have merit, your next task is to prepare for the trial.

PMID- 18816969
TI  - In search morally intelligent health care reform.
AB  - The health care policy debate is bitterly divisive because so much money is
      involved. Politicians want to keep the passionate debate going instead of acting.
      Why commit political suicide by opposing insurance and drug companies instead of
      prospering by hooking up with them?

PMID- 18816970
TI  - How do we achieve service excellence?

PMID- 18816971
TI  - Baseline measurement of running away among youth in foster care.
AB  - The current study evaluated the use of various behavioral measures of running
      away with regard to (a) the differential utility of interval- versus event-based
      measures, (b) the differential utility of rate versus duration measures, (c) the
      utility of correcting for occurrence opportunity, and (d) the influence of unit
      of analysis (i.e., single-subject vs. grouped data). Seven different baseline
      measures were calculated for 84 runaways, and a unit-size analysis was conducted
      by constructing groups of various sizes from the original sample. An expert panel
      evaluated the suitability of the baseline measures for treatment evaluation.
      Results demonstrate the utility of evaluating duration-based measures and
      correcting for occurrence opportunity. Results also indicate that single-subject
      baselines may often be unacceptable for treatment evaluations, regardless of the
      type of measure selected for use.

PMID- 18816972
TI  - Progressing toward data intimacy: a review of within-session data analysis.
AB  - Visual inspection of data is a common method for understanding, responding to,
      and communicating important behavior-environment relations in single-subject
      research. In a field that was once dominated by cumulative, moment-to-moment
      records of behavior, a number of graphic forms currently exist that aggregate
      data into larger units. In this paper, we describe the continuum of aggregation
      that ranges from distant to intimate displays of behavioral data. To aid in an
      understanding of the conditions under which a more intimate analysis is warranted
      (i.e., one that provides a richer analysis than that provided by condition or
      session aggregates), we review a sample of research articles for which within
      session data depiction has enhanced the visual analysis of applied behavioral
      research.

PMID- 18816973
TI  - An exploratory analysis of task-interspersal procedures while teaching object
      labels to children with autism.
AB  - Research has demonstrated that interspersing mastered tasks with new tasks
      facilitates learning under certain conditions; however, little is known about
      factors that influence the effectiveness of this treatment strategy. The initial
      purpose of the current investigation was to evaluate the effects of similar
      versus dissimilar interspersed tasks while teaching object labels to children
      diagnosed with autism or developmental delays. We then conducted a series of
      exploratory analyses involving the type of reinforcer delivered for correct
      responses on trials with unknown or known object labels. Performance was enhanced
      under the interspersal condition only when either brief praise was delivered for
      all correct responses or presumably more preferred reinforcers were provided for
      performance on known trials rather than on unknown trials.

PMID- 18816974
TI  - Further evaluation of leisure items in the attention condition of functional
      analyses.
AB  - Research suggests that including leisure items in the attention condition of a
      functional analysis may produce engagement that masks sensitivity to attention.
      In this study, 4 individuals' initial functional analyses indicated that behavior
      was maintained by nonsocial variables (n = 3) or by attention (n = 1). A
      preference assessment was used to identify items for subsequent functional
      analyses. Four conditions were compared, attention with and without leisure items
      and control with and without leisure items. Following this, either high- or low
      preference items were included in the attention condition. Problem behavior was
      more probable during the attention condition when no leisure items or low
      preference items were included, and lower levels of problem behavior were
      observed during the attention condition when high-preference leisure items were
      included. These findings suggest how preferred items may hinder detection of
      behavioral function.

PMID- 18816975
TI  - Using real-time visual feedback to improve posture at computer workstations.
AB  - The purpose of the current study was to examine the effects of a multicomponent
      intervention that included discrimination training, real-time visual feedback,
      and self-monitoring on postural behavior at a computer workstation in a simulated
      office environment. Using a nonconcurrent multiple baseline design across 8
      participants, the study assessed the effects of the intervention across three
      postural variables. Following an information phase, the intervention started for
      the lowest stable postural variable. The intervention led to substantial
      improvements in safety behavior for most targeted postural variables. A reversal
      to the information phase for 2 participants did not lead to decreases in safety.
      Postures self-monitored with high accuracy improved to a greater degree than
      postures self-monitored with low accuracy.

PMID- 18816976
TI  - Teaching children with autism to respond to and initiate bids for joint
      attention.
AB  - A multiple baseline design across 3 children with autism was used to assess the
      effects of prompting and social reinforcement to teach participants to respond to
      an adult's bid for joint attention and to initiate bids for joint attention.
      Participants were taught to respond to an adult's bid for joint attention by
      looking in the direction of an object at which the adult pointed, by making a
      comment about the object, and by looking back at the adult. Additional training
      and reinforcement were needed to teach the participants to initiate bids for
      joint attention. Findings are discussed in terms of the social relevance of
      teaching children with autism to respond to and initiate bids for joint
      attention.

PMID- 18816977
TI  - The role of overt and covert self-rules in establishing a daily living skill in
      adults with mild developmental disabilities.
AB  - The purpose of the current study was to explore the use of overt and covert self
      rules in the acquisition, maintenance, and generalization of a chained task by
      adults with mild developmental disabilities. This research differed from previous
      research in that the experimenter did not deliver reinforcement for correct
      responses during training, and we examined the correspondence between each self
      rule statement and each subsequent response on each trial. Results showed that
      the self-rules participated in control over participants' responding, in that the
      skill was acquired and shown to generalize in the absence of experimenter
      delivered reinforcement. Moreover, performance was shown to deteriorate when the
      emission of overt, but not covert, self-rules was blocked.

PMID- 18816978
TI  - A Social Stories intervention package for students with autism in inclusive
      classroom settings.
AB  - A Social Stories intervention package was used to teach 2 students with autism to
      read Social Stories, answer comprehension questions, and engage in role plays.
      Appropriate social behaviors increased and inappropriate behaviors decreased for
      both participants, and the effects were maintained for up to 10 months. This
      intervention package appears to be useful in inclusive classroom environments and
      does not require intensive supervision of the child's behavior.

PMID- 18816979
TI  - The effects of tact and listener training on the emergence of bidirectional intra
      verbal relations.
AB  - We evaluated the effects of 2 types of training on the emergence of bidirectional
      intraverbal relations with 4 typically developing children. Tact training
      involved reinforcing foreign-language vocalizations in the presence of visual
      stimuli, and listener training involved reinforcing selections of visual stimuli
      following vocal presentations of foreign-language words. Intraverbal relations
      were tested by instructing participants to vocalize native-language equivalents
      of foreign-language words or vice versa. Both types of training produced
      increases in intraverbal responding, but the emergent relations were not always
      bidirectional.

PMID- 18816980
TI  - Using performance feedback to improve treatment integrity of classwide behavior
      plans: an investigation of observer reactivity.
AB  - The current study replicated the positive effects of performance feedback on
      treatment integrity and extended previous work by examining reactivity using a
      multiple baseline design with alternating treatments for observer-present and
      observer-absent conditions on teachers' implementation of a classwide behavior
      plan. No differences were found between conditions, and treatment integrity
      improved across all teachers, suggesting that performance feedback, rather than
      observer reactivity, was responsible for reported behavior changes.

PMID- 18816981
TI  - Decreasing problem behavior associated with a walking program for an individual
      with developmental and physical disabilities.
AB  - In the current investigation, a functional analysis suggested that positive
      reinforcement in the form of physical contact maintained the self-injurious
      behavior of a girl with developmental and physical disabilities. We used the
      information obtained from the functional analysis to develop a treatment for
      noncompliance with walking in which a therapist removed physical interaction
      following inappropriate behavior during walks.

PMID- 18816982
TI  - A preliminary analysis of instructional control in the maintenance of appropriate
      behavior.
AB  - This bridge study evaluated the effects of contingency-specifying instructions
      (CSIs) and incomplete instructions (IIs) in terms of establishing instructional
      control of appropriate behavior. Results suggested that instructional control and
      maintenance were achieved with CSIs but not with IIs. Results are discussed in
      terms of the potential use of instructional control in the maintenance of
      appropriate behavior for children with attention deficit hyperactivity disorder.

PMID- 18816983
TI  - Some effects of noncontingent positive reinforcement on multiply controlled
      problem behavior and compliance in a demand context.
AB  - Functional analysis suggested that the problem behavior of an 8-year-old girl
      with autism was maintained by escape from demands and access to edible items.
      Noncontingent delivery of an edible item was sufficient to increase compliance
      and reduce the rate of problem behavior without the use of escape extinction in a
      demand context. Leaner and richer schedules of noncontingent reinforcement were
      equally effective, and there were minimal differences between noncontingent
      reinforcement and differential reinforcement of compliance.

PMID- 18816984
TI  - A preliminary comparison of functional analysis results when conducted in
      contrived versus natural settings.
AB  - A preliminary evaluation of the correspondence between functional analysis
      outcomes across settings was conducted with 2 children who had been diagnosed
      with autism and who engaged in challenging behavior. Differences across settings
      (a therapy room and a classroom) were demonstrated in ABAB reversal designs.
      Three potential patterns of results that may occur when comparing functional
      analyses across environments are described, and one possible explanation for the
      occurrence of discrepancies between environments (differing learning histories
      within separate environments) is offered.

PMID- 18816985
TI  - Evaluating preference assessments for use in the general education population.
AB  - This study compared the effectiveness of a multiple-stimulus-without-replacement
      (MSWO) preference assessment and teacher preference ranking in identifying
      reinforcers for use in a general education setting with typically developing
      elementary-school children. The mean number of digits correctly answered was
      greater in the MSWO-selected reward and the teacher-selected reward conditions
      relative to the no-reward condition for 2 of the 4 participants, but there were
      no differences between the MSWO-selected and teacher-selected reward conditions
      for any participant.

PMID- 18816986
TI  - An evaluation of the high-probability instruction sequence with and without
      programmed reinforcement for compliance with high-probability instructions.
AB  - We assessed the effects of reinforcement and no reinforcement for compliance to
      high-probability (high-p) instructions on compliance to low-probability (low-p)
      instructions using a reversal design. For both participants, compliance with the
      low-p instruction increased only when compliance with high-p instructions was
      followed by reinforcement. These results suggest that providing reinforcement for
      high-p instructions may result in increased compliance to low-p instructions.

PMID- 18816987
TI  - Caregiver-conducted experimental functional analyses of inappropriate mealtime
      behavior.
AB  - The purpose of the current study was to replicate the use of parents as
      therapists for experimental functional analyses of inappropriate mealtime
      behavior with multiple participants while measuring procedural integrity. Clear
      functions were identified, and high percentages of procedural integrity were
      obtained.

PMID- 18816988
TI  - Contextual control of slot-machine gambling: replication and extension.
AB  - Participants were trained and tested to select stimuli of differing physical
      quantities in the presence of 2 color contextual cues for more than and less
      than. Following more than and less than relational training, participants
      allocated the majority of their responses to the slot machine that shared formal
      properties of color with the contextual cue for more than, despite the identical
      payout probabilities of the slot machines.

PMID- 18816989
TI  - 2007 North American zoo and aquarium veterinary employment survey.
AB  - A web-based survey was presented to 158 Association of Zoos and Aquariums (AZA)
      accredited zoos and 31 AZA-accredited aquariums or marine-life parks in the
      United States and Canada via e-mail. The survey included questions about
      veterinary employment and salaries. Representatives from 124 zoos and 15
      aquariums responded. Zoos and aquariums with higher operating budgets were more
      likely to employ full-time veterinarians. The number and percentage of zoos
      employing full-time zoo veterinarians have increased since the previous job
      survey that took place in 1988, with 59.6% of all responding zoos employing at
      least one full-time veterinarian. During the same time span, the proportion of
      male to female zoo veterinarians has shifted from a predominantly male group to
      an almost equal ratio. Salaries for full-time zoo and aquarium veterinarians
      ranged from $20,800 to $150,000.

PMID- 18816990
TI  - Electrocardiography of Grevy's zebras (Equus grevyi).
AB  - Electrocardiograms (ECGs) are a good baseline test for assessing cardiac rhythm.
      ECGs have not been reported in any zebra species and in very few Perissodactyla
      species. Standard limb, six-lead ECGs were recorded in 23 anesthetized Grevy's
      zebras (Equus grevyi). Heart rate, RR interval, P-wave duration, RR
      maximum/minimum, PR interval, QRS duration, QT interval, ST segment deviation, P
      wave amplitude, QRS amplitude, and T-wave amplitude were measured and calculated
      from lead II ECGs from these Grevy's zebras. Several variables were tested,
      including gender, age (0-24, 24-48, 48-180, and >180 mo), weight (<350 kg or >350
      kg), pregnancy status, and anesthetic differences (standard dose or supplemented
      dose), to see if they affected ECG values in these animals. There were no
      significant differences in any of the ECG parameters between genders. RR and QT
      intervals were longer in older zebras; heart rates were faster in younger zebras.
      The RR and PR intervals, as well as the QRS duration, were greater in heavier
      zebras; heart rates were faster in lighter zebras. The RR interval was
      significantly longer in pregnant zebras. There were no significant differences in
      any of the ECG parameters for zebras anesthetized with a standardized dose of the
      drug combination etorphine-detomidine-acepromazine compared to those receiving
      additional supplements of these drugs and/or ketamine. All other parameters were
      not significantly different among groups, except where noted previously. The
      results of this research indicate that differences in ECG parameters in zebras
      may occur between animals of different ages, weights, and pregnancy status and
      that these factors should be considered when interpreting the respective ECGs of
      these zebras.

PMID- 18816991
TI  - Aleutian disease serology, protein electrophoresis, and pathology of the European
      mink (Mustela lutreola) from Navarra, Spain.
AB  - The European mink, Mustela lutreola, has suffered a dramatic decline in Europe
      during the 20th century and is one of the most endangered carnivores in the
      world. The subpopulation of European mink from Navarra, Spain, estimated to
      number approximately 420, represents approximately two thirds of the total number
      of mink in Spain. Aleutian Disease Virus (ADV) is a parvovirus with a high degree
      of variability that can infect a broad range of mustelid hosts. The pathogenesis
      of this virus in small carnivores is variable and can be influenced by both host
      factors (e.g., species, American mink genotype, and immune status) and viral
      strain. A cross-sectional study was conducted during the pre-reproductive period
      of February-March 2004 and 2005 and the postreproductive period of September
      December 2004. Mink were intensively trapped along seven rivers that were
      representative of the European mink habitat in Navarra. Antibody counter
      immunoelectrophoresis against ADV was performed on 84 European mink blood
      samples. All the samples were negative. Protein electrophoresis was performed on
      93 plasma samples. Nine of those samples (9.6%) had gamma globulin levels
      exceeding 20% of the total plasma protein. Complete necropsies were performed on
      23 cadavers of European mink collected in the area between 2000 and 2005.
      Seventeen of the mink (74%) had traumatic and hemorrhagic lesions compatible with
      vehicular impact injuries. Although there were no histopathologic lesions
      associated with ADV, this study documents the first description of a naturally
      occurring canine distemper virus infection in a European mink. In addition,
      pulmonary adiaspiromycosis in three European mink from Spain was reported.

PMID- 18816992
TI  - Electrocardiographic parameters of captive lions (Panthera leo) and tigers
      (Panthera tigris) immobilized with ketamine plus xylazine.
AB  - Twenty-seven healthy captive lions (Panthera leo) and 13 healthy captive tigers
      (Panthera tigris) from Sao Paulo Zoo (Fundacao Parque Zoologico de Sa Paulo, Sao
      Paulo, Brazil) collection were selected for this study. They were anesthetized
      with ketamine (10 mg/kg) combined with xylazine (1-2 mg/kg) for physical
      examinations, hematologic and serum chemical analysis and electrocardiogram
      recording. The main aim of this research was to gather initial information about
      normal electrocardiographic parameters of large felids. Standard P-QRS-T
      deflections on leads described for domestic carnivores were analyzed, and they
      did not greatly differ from those of large felids, taking into account the
      greater weight and corporal mass of large felids. Heart rate of lions ranged from
      42 to 76 beats per minute (bpm). Heart rate of tigers ranged from 56 to 97 bpm.
      In both species, the most common rhythm detected was normal sinus rhythm followed
      by sinus arrhythmia; wandering pacemaker was also observed with normal sinus
      rhythm or sinus arrhythmia. Mean electrical axis lay between +60 degrees and +120
      degrees. QRS complexes were predominantly positive in leads DI, DII, DIII, and
      AVF, and negative in AVR and AVL. This study provides insights into normal
      electrocardiograms of large felids. Wider investigations on the same subject are
      necessary to establish criteria for the recognition of abnormalities in these
      species and should include other anesthetic drug(s) combinations and reports of
      electrocardiographic features of animals with cardiac disease and electrolytes
      disturbances.

PMID- 18816993
TI  - Distal limb radiography, ossification, and growth plate closure in the juvenile
      Asian elephant (Elephas maximus).
AB  - Eleven juvenile Asian elephants (Elephas maximus) were evaluated radiographically
      to determine the relative times of growth plate closure and phalangeal
      ossification in the bones of the distal forelimb. Specifically, the first,
      second, and third phalanges of the third digit (D3) were evaluated, as well as
      the third phalanx of digits 1, 2, 4, and 5. All elephants were healthy at the
      time of examination. A retrospective evaluation of radiographs from six of the 11
      juvenile elephants was also completed to augment the data set. This study reports
      the methods used to obtain high-quality radiographs of the distal juvenile
      elephant limb, ossification characteristics of the phalanges, relative times of
      growth plate closure within the proximal phalanges of D3, and a method for age
      estimation based on radiographic findings. This study will help clinicians in
      conducting elephant foot radiography, in evaluating foot radiographs in juvenile
      elephants, in recognizing normal versus pathologic change, and in estimating
      juvenile elephant age based on radiographic ossification characteristics and
      growth plate closure times. Consistent use of the proposed foot radiograph
      technique is recommended to facilitate foot disease recognition and as part of
      the annual examination of captive Asian elephants.

PMID- 18816994
TI  - Seroprevalence of retrovirus in North American captive macropodidae.
AB  - Laboratory records of serology results from captive macropodidae sampled between
      1997 and 2005 were reviewed to assess the seroprevalence of retrovirus exposure.
      Serum samples from 269 individuals (136 males, 133 females) representing 10
      species of macropods housed in 31 North American captive collections were
      analyzed for retrovirus antibody using an indirect immunofluorescent assay. The
      prevalence of positive antibody titers comparing male versus female, between
      species, between age groups, and among animals with identified parentage was
      examined by nonparametric statistical analyses. Median age of animals at time of
      sample collection was 36 mo (range 2-201 mo). Total percentage seropositive was
      20.4%. Serum antibody was detected in 31 of 47 (66.0%) tammar wallaby (Macropus
      eugenii), nine of 24 (37.5%) yellow-footed rock wallaby (Petrogale xanthopus),
      four of 11 (36.4%) swamp wallaby (Wallabia bicolor), 10 of 80 (12.5%) red-necked
      wallaby (Macropus rufogriseus), and one of 54 (1.9%) parma wallaby (Macropus
      parma). No individuals of western gray kangaroo (n=3) (Macropus fuliginosus),
      eastern gray kangaroo (n=19) (Macropus giganteus), common wallaroo (n=6)
      (Macropus robustus), red kangaroo (n=11) (Macropus rufus), or Matschie's tree
      kangaroo (n=14) (Dendrolagus matschiei) were positive for retrovirus antibody.
      These results demonstrate that five species of captive macropods have a history
      of exposure to retrovirus, with the highest percentage seropositive and highest
      statistical correlation in M. eugenii (pair-wise Fisher's exact test, alpha =
      0.05). Additionally, one wild-caught M. eugenii was confirmed seropositive during
      quarantine period, indicating that retrovirus exposure may exist in wild
      populations.

PMID- 18816995
TI  - Comparison of the somatotropic axis in free-ranging and rehabilitated harbor seal
      pups (Phoca vitulina).
AB  - The somatotropic axis, including growth hormone (GH), insulin-like growth factor
      (IGF)-I, and IGF binding proteins (IGFBP), is a bridge between growth physiology,
      developmental age, and nutritional status in domestic animals. However, the
      importance of the somatotropic axis in nutrition, growth, and development of
      harbor seals has not been previously explored. Given the difficulty of conducting
      longitudinal studies in free-ranging harbor seals, this study focused on the
      potential use of harbor seals in rehabilitation facilities as a model for free
      ranging seals. The purpose of this research was to compare concentrations of
      components of the somatotropic axis in free-ranging versus rehabilitated harbor
      seal pups. The hypothesis was that measurements of the somatotropic axis will be
      similar between individuals of comparable age and nutritional status (fasting
      versus feeding). To investigate this hypothesis, harbor seal pups (n=8) brought
      to The Marine Mammal Center (Sausalito, California, USA) or Mystic Aquarium
      (Mystic, Connecticut, U.S.A.) were initially assessed and determined to be
      healthy but abandoned. All pups were less than 2 wk of age upon arrival at
      rehabilitation facilities. Standard length was assessed at the time of arrival
      and again at release. Body mass was measured every week and blood samples were
      collected from each pup at 0, 4, and 8 wk of rehabilitation. Blood was collected
      and morphometrics assessed in free-ranging harbor seal pups (n=8) from the Gulf
      of Maine. Sera were analyzed for GH, IGF-I, and IGFBP concentrations.
      Concentrations of GH, IGF-I, and IGFBP-2 and -3 in rehabilitated pups were within
      a similar range compared with free-ranging pups when considered in the context of
      presumed nutrient intake. These data suggest that rehabilitated harbor seals may
      provide a useful model to investigate the effects of nutrient intake on growth
      and development of harbor seals, and will provide insight into phocid
      endocrinology and metabolism.

PMID- 18816996
TI  - Urinalysis in three species of captive rhinoceros (Rhinoceros unicornis,
      Dicerorhinus sumatrensis, and Diceros bicornis).
AB  - This study reports urinalysis values for three species of captive rhinoceros
      (Rhinoceros unicornis, Dicerorhinus sumatrensis, and Diceros bicornis) and
      evaluates individual and species differences. Repeated urinalysis was conducted
      on 11 individuals to establish normal reference ranges. Although no individual or
      species differences existed in urinary values for pH, all species differed in
      specific gravity. Rhinoceros urine demonstrated many physical and chemical
      properties similar to that of the horse, but reliability of this comparison was
      limited. Urinary pH in the rhinoceros was within range of that established for
      the horse and other large herbivores. However, all rhinoceros species exhibited
      urinary specific gravities below the lower limit of the normal equine reference
      range. Comparative urinalysis using an outside laboratory source confirmed the
      results of this study and illustrated the value of conducting in-house analysis.
      These results are the first data available on reference ranges for urine
      parameters in the greater one-horned, Sumatran, and African black rhinoceros and
      provide a useful diagnostic tool for the veterinary care of individuals in
      captivity.

PMID- 18816997
TI  - Measuring agreement and discord among hemagglutination inhibition assays against
      different ophidian paramyxovirus strains in the Eastern massasauga (Sistrurus
      catenatus catenatus).
AB  - At present, the hemagglutination inhibition (HI) assay is the sole commercially
      available serologic method available to detect exposure to ophidian paramyxovirus
      (OPMV) in snakes. During 2006, 26 eastern massasaugas (Sistrurus catenatus
      catenatus) were collected, and blood was sampled to determine their OPMV status.
      Samples from each snake were divided into 3 aliquots and tested by using
      commercially available HI assays against the 4 OPMV isolates used in the 3
      laboratories that offer the service. All snakes were tested for antibodies by
      using HI assays against the green tree python (GTP), San Lucan rattlesnake (SLR),
      and Aruba Island rattlesnake (AIR) isolates. Twenty-five snakes were tested for
      antibodies against the western diamondback rattlesnake (WDR) isolate. All samples
      tested against the GTP and SLR were positive (26/26), whereas 56% (14/25) of the
      WDR assays were positive, and none (0/26) of the AIR assays yielded a positive
      result. There was 100% agreement between the GTP and SLR assays, and complete
      disagreement between the SLR and AIR, as well as the GTP and AIR assays. Kappa
      statistics for the GTP-WDR, SLR-WDR, GTP-AIR, SLR-AIR, and WDR-AIR indicated that
      the assays had less than chance agreement. The results demonstrate that current
      HI assays are not reliable as a sole diagnostic assay in the eastern massasauga.
      Furthermore, HI assays need to be evaluated by using other parameters to
      determine OPMV exposure in eastern massasaugas.

PMID- 18816998
TI  - Fatal toxoplasmosis in sand cats (Felis margarita).
AB  - The sand cat (Felis margarita) is a small-sized felid occurring in the United
      Arab Emirates (UAE). The sand cat captive-breeding program at the Breeding Centre
      for Endangered Arabian Wildlife in Sharjah, UAE, has until recently been severely
      compromised by very high newborn mortality rates. Two different pairs of sand
      cats gave birth, respectively, to one and two litters (with a total of eight
      kittens) between 1999 and 2006. Seven out of eight kittens died between the third
      and 21st wk of life. Toxoplasmosis was confirmed as the cause of death in these
      two litters. Adult cats had high antibody titers to Toxoplasma gondii before
      pregnancy, suggesting that maternal immunity did not protect the kittens against
      infection with T. gondii and that maternal immunity might not have prevented
      transplacental transmission of the parasite. This observation contrasts with what
      is seen in domestic cats. To date, this is the first report on confirmed fatal
      toxoplasmosis and prevalence of T. gondii in sand cats.

PMID- 18816999
TI  - A survey of amoebic infections and differentiation of an Entamoeba histolytica
      like variant (JSK2004) in nonhuman primates by a multiplex polymerase chain
      reaction.
AB  - A pathogenic Entamoeba histolytica-like variant (JSK2004 strain) with genetic
      variations and a novel isoenzyme pattern isolated from a De Brazza's guenon in a
      Tokyo zoo in Japan has previously been documented. In this study, a multiplex
      polymerase chain reaction (PCR) assay that could distinguish the JSK2004-type E.
      histolytica-like variant (JSK04-Eh-V) from E. histolytica and Entamoeba dispar
      using three newly designed primer sets for amplifying each specific DNA fragment
      from their small-subunit ribosomal RNA genes was developed and established. Forty
      seven primates (11 species) from the zoo were surveyed by multiplex PCR to assess
      the prevalence of JSK04-Eh-V infection, which was recognized in six individuals
      of four species, including an Abyssinian colobus monkey, a De Brazza's guenon
      (including the individual from whom JSK2004 was isolated), a white-faced saki,
      and a Geoffroy's spider monkey. In addition, the autopsied individuals of an
      Abyssinian colobus and Geoffroy's spider monkey that died of amoebic liver
      abscess were also evaluated. DNA samples were also analyzed for specific
      genotypes based on the nucleotide sequencing of two protein-coding (chitinase and
      serine-rich E. histolytica protein) genes and the protein-noncoding locus 1-2
      that was used for fingerprinting of the E. histolytica strain. These studies
      indicated that the E. histolytica-like variant infection in this zoo was caused
      by the same type (i.e., JSK04-Eh-V). An axenic culture medium (yeast extract-iron
      maltose-dihydroxyacetone-serum) was developed based on the yeast extract-iron
      gluconic acid-dihydroxyacetone-serum medium, which is designed for axenic culture
      of E. dispar. This new medium could be used for axenically culturing E.
      histolytica, JSK04-Eh-V, and E. dispar in a single medium.

PMID- 18817000
TI  - Development of a management program for a mixed species wildlife park following
      an occurrence of malignant catarrhal fever.
AB  - During late 2001 and early 2002, a mixed species wildlife park in North Carolina
      experienced an acute outbreak of morbidity and mortality in Pere David's deer
      (Elaphurus davidianus), axis deer (Axis axis), blackbuck antelope (Antelope
      cervicapra), white-tailed deer (Odocoileus virginianus), and Rocky Mountain elk
      (Cervus elaphus). Clinical signs varied from fulminant disease, progressing from
      depression to bloody scours to death in fewer than 4 days in Pere David's deer,
      to a more protracted form of disease, ranging from 2 wk to 3 mo, in axis deer. In
      moribund axis deer, high levels of anti-malignant catarrhal fever (MCF) virus
      antibody by competitive-inhibition enzyme-linked immunosorbent assay were
      detected. Ovine herpesvirus 2 (OvHV-2) DNA was detected in peripheral blood
      leukocytes of the affected axis deer. No other MCF viruses were detected.
      Retrospective examination of frozen tissue samples from the affected Pere David's
      deer and blackbuck antelope also confirmed the presence of OvHV-2 DNA. Initial
      control efforts were directed at preventing further deaths of clinically
      susceptible animals by removing MCF virus reservoir species, particularly ovine
      species. The most prevalent ovine species in the wildlife park was mouflon sheep
      (Ovis musimon). All sheep were removed from the park by June 2002, and the last
      MCF death occurred in October 2002. Since mouflon sheep had been a prominent
      attraction in the wildlife park, the owner wanted a means to reintroduce this
      species to the park. Derivation of OvHV-2-uninfected mouflon lambs was undertaken
      using the previously described program for production of OvHV-2-free sheep (Ovis
      ovis). The rederived MCF virus-negative mouflon sheep were introduced into the
      park in approximately January 2004. As of December 2007, no further cases of MCF
      have occurred since the removal of OvHV-2-positive mouflon sheep and
      reintroduction of the virus-free lambs. This paper describes the successful
      management and control of MCF in a densely populated mixed species animal park.

PMID- 18817001
TI  - Disseminated tuberculosis in hyrax (Procavia capensis) caused by Mycobacterium
      africanum.
AB  - Tuberculosis due to Mycobacterium africanum was diagnosed in an adult female
      hyrax (Procavia capensis). Pathologic examination revealed disseminated
      tuberculous lesions. The same pathologic changes were also found in a male hyrax
      that died a year later. Both animals were imported from the United Arab Emirates
      and were held in captivity at the Zagreb Zoo in Croatia. The source of infection
      remains unknown. The acid-fast bacteria isolated from the lungs of the female
      hyrax were identifyed by polymerase chain reaction as Mycobacterium tuberculosis
      complex and Geno Type MTBC test confirmed the strain to be M. africanum I.

PMID- 18817002
TI  - Spontaneous neoplasia in four captive greater hedgehog tenrecs (Setifer setosus).
AB  - Little information is available about diseases and pathology of species within
      the family Tenrecidae, including the greater hedgehog tenrec (Setifer setosus), a
      Madagascan insectivore. This report summarizes necropsy and histopathologic
      findings of neoplasia in four captive greater hedgehog tenrecs. Although only
      four animals are included in this report, neoplasia seems to be a common and
      significant source of morbidity and mortality in greater hedgehog tenrecs. Types
      of neoplasia identified include a thyroid follicular-solid carcinoma, two urinary
      bladder transitional cell carcinomas, uterine endometrial polyps, and
      multicentric B-cell lymphoma. Due to small sample size, no etiology could be
      determined, but genetics, viral infection, pesticide treatment, nutrition, or
      other environmental factors might contribute to the development of neoplasia in
      this species. This is the first report of neoplasia in greater hedgehog tenrecs.

PMID- 18817003
TI  - Idiopathic infertility in two captive male gerenuk (Litocranius walleri walleri).
AB  - Two adult male gerenuk (Litocranius walleri walleri) were confirmed infertile
      with distinctly varying clinical presentations. One animal had unilateral
      testicular degeneration/hypoplasia, and within 8 mo experienced
      atrophy/degeneration of the remaining testicle. The second animal had been
      previously treated with melengesterol acetate (MGA) milled in feed for 1 yr
      during puberty as part of an aggression-control study. The testes in this
      individual appeared normal both visually and on palpation; however, repeated
      semen collection consistently produced ejaculates containing high numbers of
      immotile spermatozoa, all of a single abnormal morphology: shortened tails, with
      normal total sperm counts for this species. Both gerenuk had cortisol
      concentrations within normal ranges for adult male gerenuk. Analysis of serum
      mineral concentration revealed zinc levels that would be considered low in
      domestic cattle. Testosterone levels were low for the animal discussed in case 1,
      but were within normal range for the animal in case 2 compared with other
      gerenuk. Investigations into endocrine causes, such as abnormal thyroid hormone
      concentrations and adrenal function, were unrewarding. Both animals discussed in
      this report are maternally related; therefore, a genetic cause of infertility
      cannot be ruled out. Further investigation into MGA, as well as the dietary zinc
      requirements for gerenuk, and resulting effects on spermatogenesis and testicular
      development are warranted.

PMID- 18817004
TI  - Chytridiomycosis in an aquarium collection of frogs: diagnosis, treatment, and
      control.
AB  - The introduction of a new group of dendrobatid frogs to an established captive
      amphibian collection was followed by several acute mortalities in both resident
      and introduced frog populations. Chytridiomycosis, caused by Batrachochytrium
      dendrobatidis, was diagnosed by histology in two of the dead frogs. Following the
      diagnosis, all amphibians were moved to a specially made quarantine room with
      strict handling protocols and treated with itraconazole. Frogs, being terrestrial
      amphibians, were treated with itraconazole (Sporanox, 10 mg/ml) at 0.01% in 0.6%
      saline in a 5-min bath for 11 consecutive days. Axolotls (Ambystoma mexicanum)
      and Kaup's caecilians (Potymotyphlus kaupii), being aquatic amphibians, were
      treated with itraconazole administered directly in their primary tank water to
      achieve a concentration of 0.01% for 30 min every 5 days for four treatments.
      Itraconazole was removed from the tank water after 30 min by high-rate-of-flow
      activated charcoal filters. The treatment and quarantine procedures were
      successful in eradicating the disease. The few amphibian mortalities that
      occurred in the 18 mo after the start of the treatment have been histologically
      negative for the presence of chytrid fungi. The collection is now considered free
      of chytridiomycosis.

PMID- 18817005
TI  - Disseminated panniculitis in a bottlenose dolphin (Tursiops truncatus) due to
      Mycobacterium chelonae infection.
AB  - A 14-year-old female bottlenose dolphin was diagnosed with mycobacterial
      panniculitis based on punch biopsy specimens. The necropsy revealed numerous
      pyogranulomas in the blubber, as well as marked acute multifocal necrosuppurative
      pneumonia and lymphadenitis. In addition, the animal had marked scoliosis, which
      had first been noted clinically in the dolphin at about 1 mo of age. The animal
      had been treated with low-dose dexamethasone for approximately the last 19 mo to
      reduce perceived discomfort from spondyloarthritis and with the progestational
      agent altrogenest for approximately 8 yr to prevent pregnancy. Acid-fast positive
      bacilli were detected in the dermis but not in lung or lymph nodes. Mycobacterium
      chelonae was isolated from pooled skin, lung, and peripheral lymph-node tissue.
      Mycobacterial infection may be considered as a differential diagnosis in
      bottlenose dolphins with generalized cutaneous inflammation, particularly if
      chronic steroid and progesterone treatments were administered, both of which may
      have an immunomodulatory effect.

PMID- 18817006
TI  - Diagnosis and surgical treatment of a Chiari I-like malformation in an African
      lion (Panthera leo).
AB  - A 13-mo-old intact male African lion (Panthera leo) presented with a 3-mo history
      of lethargy, ventral flexion of the neck, abnormal vocalization, and ataxia.
      Hemogram and serum biochemistries were within normal limits except for the
      presence of hypokalemia (2.7 mEq/L) and hypochloridemia (108 mEq/L). When no
      improvement was noted with oral potassium gluconate supplementation, a computed
      tomography scan of the brain and skull was performed, and no abnormalities were
      noted. However, magnetic resonance imaging detected occipital bone thickening,
      crowding of the caudal cranial fossa with cerebellar compression and herniation,
      and cervical syringohydromyelia, which was consistent with a Chiari I-like
      malformation. Foramen magnum decompression was performed to relieve the
      compression of the cerebellum. The animal recovered well with subsequent
      resolution of clinical signs. Hypovitaminosis A has been proposed previously as
      the underlying etiology for this malformation in lions with similar clinical
      presentations. This lion's serum and liver vitamin A concentrations were low (100
      ng/ml and 25.31 microg/g, respectively) compared to concentrations reported for
      domestic carnivores and support hypovitaminosis A as the underlying cause of this
      animal's Chiari I-like malformation.

PMID- 18817007
TI  - Mycotic proventriculitis in gray partridges (Perdix perdix) on two game bird
      farms.
AB  - Proventriculitis and chronic respiratory disease were diagnosed in two flocks of
      gray partridges (Perdix perdix) on unrelated Swedish game bird farms. Affected
      birds showed loss of condition, respiratory signs, and flock mortality rates of
      50 and 98%, respectively. The proventricular lesions were associated closely with
      fungal organisms that were microscopically indistinguishable from the
      ascomycetous yeast Macrorhabdus ornithogaster (former provisional name
      "megabacterium"). At necropsy, the proventriculi were swollen and hyperemic, and
      viscous mucus adhered to the mucosa. Proventricular hemorrhages were commonly
      detected, and one bird had proventricular rupture and peritonitis.
      Microscopically, mild to severe subacute to chronic lymphoplasmacytic
      proventriculitis, microabscesses, necrosis, epithelial metaplasia, disrupted
      koilin, ulcers, and hemorrhages were observed. Transmission electron microscopy
      of the proventricular microorganisms revealed a membrane-bound nucleus, vacuoles,
      ribosomes, microtubules in parallel arrays, and a two-layered cell wall but no
      mitochondria. Scanning electron microscopy of the proventricular epithelium
      demonstrated masses of organisms with occasional constrictions in parallel
      arrangement. Many of the birds also suffered from concurrent respiratory
      bacterial infections and/or gastrointestinal candidiasis. The clinical course and
      gross and microscopic proventricular lesions were similar to those described in
      psittacine and passerine pet birds colonized by M. ornithogaster-like
      microorganisms but differed from published case reports and experimental
      infections of chickens in which the clinical signs and lesions have been
      considerably milder. The findings presented in this paper suggest that mycotic
      proventriculitis, presumably associated with M. ornithogaster, may be a serious
      but possibly opportunistic, although unusual, disease problem in gray partridges
      on game farms.

PMID- 18817008
TI  - Antibiotic intravenous regional perfusion for successful resolution of distal
      limb infections: two cases.
AB  - Intravenous regional perfusion is a common technique for treating infections of
      the extremities in humans and horses. It has the advantage of achieving very high
      antibiotic concentrations in affected tissues. This technique was used to
      clinically resolve deep, mixed infections involving bones and joints in a swamp
      wallaby and a lesser kudu. Both infections were severe and considered life
      threatening, because amputation was not feasible, systemic antibiotic treatment
      had failed, and both animals were in pain and had evidence of the systemic
      effects of the infections. In the wallaby, once daily treatments with imipenem
      for 5 days resulted in a return to normal function within 1 mo. In the kudu, four
      treatments using both ampicillin/sulbactam followed by enrofloxacin were
      performed every 2 days, followed by two treatments with ampicillin/sulbactam
      alone 2 wk later. Resolution of this case was achieved in less than 2 mo. The
      only adverse effect noted was phlebitis in the kudu, which resolved with
      conservative therapy. Healing was rapid in both cases and was apparent after two
      treatments. This report demonstrates the efficacy and flexibility of intravenous
      regional perfusion for the treatment of severe infections of the digits in
      nondomestic species.

PMID- 18817009
TI  - Concurrent infection with ranavirus, Batrachochytrium dendrobatidis, and
      Aeromonas in a captive anuran colony.
AB  - Four species (Dendrobates auratus, Phyllobates terribilis, Pyxicephalus
      adspersus, and Rhacophorus dennysi) of captive anurans with a clinical history of
      lethargy and inappetence were found dead and were submitted for necropsy. Gross
      lesions included irregular patches of sloughed skin and rare dermal ulcerations.
      Histologic findings included epidermal proliferation that was most pronounced on
      the digits and that included intracytoplasmic chytrid organisms. Bacteria were
      often associated with the epidermal lesions. Intracytoplasmic inclusion bodies
      were observed in hepatocytes. Real-time polymerase chain reaction yielded
      positive results for both Ranavirus and Batrachochytrium dendrobatidis (Bd).
      Bacterial culture of internal organs yielded Aeromonas hydrophila. This is the
      first report of concurrent infections in anurans by Ranavirus and Bd and A.
      hydrophila.

PMID- 18817010
TI  - Molecular findings of disseminated histoplasmosis in two captive snow leopards
      (Uncia uncia).
AB  - This paper reports two cases of disseminated histoplasmosis in captive snow
      leopards (Uncia uncia). Histoplasmosis was diagnosed based on histopathology,
      immunohistochemistry, transmission electron microscopy, and molecular findings.

PMID- 18817011
TI  - Sub-occipital craniectomy in a lion (Panthera leo) with occipital bone
      malformation and hypovitaminosis A.
AB  - Neurologic dysfunction accompanied by malformation of both the skull and the
      cervical vertebrae has been previously described in lions kept in captivity
      worldwide, and this dysfunction and malformation were most often related to
      vitamin A deficiency. Diagnosis of the bone malformation and its effects on the
      neural tissue was until recently limited to postmortem examination, with
      characteristic thickening of the bones of the cranial vault, cerebellar
      herniation, compression of the foramen magnum, and enlargement of the lateral
      ventricles. For some mildly affected lion cubs with neurologic signs, improvement
      was reported with excessive vitamin A supplementation. However, definitive
      diagnosis was only available for those that eventually died or were euthanized.
      This case documents the antemortem diagnosis of the disease using computed
      tomographic imaging and liver biopsy. While conservative treatment failed,
      suboccipital craniectomy removed the thickened occipital bone and was
      demonstrated to be a successful surgical intervention that can be used to treat
      more severely affected lions.

PMID- 18817012
TI  - Hematology of the Pascagoula map turtle (Graptemys gibbonsi) and the southeast
      Asian box turtle (Cuora amboinensis).
AB  - Turtle populations are decreasing dramatically due to habitat loss and collection
      for the food and pet market. This study sought to determine hematologic values in
      two species of turtles to help assess health status of captive and wild
      populations. Blood samples were collected from 12 individuals of the Pascagoula
      map turtle (Graptemys gibbonsi) and seven individuals of the southeast Asian box
      turtle (Cuora amboinensis) from the Savannah River Ecology Laboratory (South
      Carolina, USA). The hematologic data included hematocrit, total solids,
      erythrocyte count, leukocyte count, and differential and percentage leukocyte
      counts. Low hematocrit values and high basophil counts were found in both
      species. The basophil was the most abundant leukocyte in the Pascagoula map
      turtle (median = 0.80 x 10(9)/L), whereas in the Southeast Asian box turtle the
      most abundant leukocyte was the heterophil (median = 2.06 x 10(9)/L).

PMID- 18817013
TI  - Complicated urethral rupture and scrotal urethrostomy in a Bongo antelope
      (Tragelaphus eurycerus isaaci).
AB  - A 4-yr-old, 300-kg male Bongo antelope presented a fluctuant swelling on the
      ventral abdomen surrounding the penis, which was confirmed later as compatible
      with urethral rupture. Initial treatment included broad-spectrum antibiotic and
      radical surgical debridement. Total prepuce and partial penile amputation with
      orchidectomy was performed and normal micturition was restored. At a later stage,
      when the extent of the lesion was controlled, a permanent scrotal urethrostomy
      was performed. Complete healing by second intention was achieved 2 mo after the
      last surgery. Although the outcome was very good, considering the extent and
      severity of the tissue damage, prompt permanent urethrostomy when urethral
      rupture was first suspected would have prevented deterioration of the condition
      and prevented the need for extensive surgery.

PMID- 18817014
TI  - Continuous lumbar hemilaminectomy for intervertebral disc disease in an Amur
      tiger (Panthera tigris altaica).
AB  - A 13-yr-old Amur tiger (Panthera tigris altaica) was presented for an acute onset
      of paraplegia. Spinal imaging that included plain radiographs, myelography, and
      computed tomography performed under general anesthesia revealed lateralized
      spinal cord compression at the intervertebral disc space L4-5 caused by
      intervertebral disc extrusion. This extrusion was accompanied by an extensive
      epidural hemorrhage from L3 to L6. Therefore, a continuous hemilaminectomy from
      L3 to L6 was performed, resulting in complete decompression of the spinal cord.
      The tiger was ambulatory again 10 days after the surgery. This case suggests that
      the potential benefit of complete spinal cord decompression may outweigh the risk
      of causing clinically significant spinal instability after extensive
      decompression.

PMID- 18817015
TI  - Chemotherapy and radiotherapy for treatment of cutaneous lymphoma in a ground
      cuscus (Phalanger gymnotis).
AB  - A 15-year-old female ground cuscus (Phalanger gymnotis) was presented with an
      isolated ulcerated, nonhealing lesion on the lateral thorax. Histopathology and
      immunohistochemistry were diagnostic for cutaneous T-cell lymphoma with
      incomplete excision. Oral chemotherapy with CCNU (lomustine) resulted in clinical
      remission that lasted 255 days, with no appreciable toxicity. Tumor recurrence
      was treated with radiation therapy, which resulted in 120 additional days of
      clinical remission. Subsequently, the tumor developed at a distant site and the
      cuscus was humanely euthanized. A slight decrease in appetite early in disease
      progression was the only adverse effect noted throughout the treatment period.
      Oral, minimally invasive chemotherapy, and adjunct radiation therapy were viable
      treatment options for this ground cuscus and should be considered for treatment
      of neoplasia in other nontraditional species.

PMID- 18817016
TI  - Repeat laparotomy for the treatment of septic peritonitis in a Bornean orangutan
      (Pongo pygmaeus pygmaeus).
AB  - A 9-yr-old female Bornean orangutan (Pongo pygmaeus pygmaeus) presented with a 48
      hr history of depression, lethargy, anorexia, and mucoid discharge from the
      rectum. Clinical, radiographic, and ultrasonographic examination demonstrated the
      presence of multiple distended loops of intestine, intestinal adhesions, and free
      gas within the abdomen. During exploratory laparotomy, fibrinopurulent diffuse
      peritonitis as a result of a ruptured intrapelvic abscess with associated large
      bowel adhesions was evident. The abdomen was thoroughly lavaged, necrotic debris
      and abscess wall removed, and fibrinous adhesions disrupted. The orangutan was
      kept sedated for 48 hr to allow for intensive care. Six months later, when the
      orangutan presented with similar clinical signs, ultrasonographic examination
      demonstrated the presence of a pelvic abscess. The previous procedure was
      repeated with the addition of a hysterectomy. This report is the first
      documentation of long-term management following surgical intervention for
      internal abdominal abscessation and septic peritonitis in a great ape.

PMID- 18817017
TI  - Evaluation of intramuscular butorphanol, azaperone, and medetomidine and nasal
      oxygen insufflation for the chemical immobilization of white-tailed deer,
      Odocoileus virginianus.
AB  - Chemical immobilization of wildlife often includes opioids or cyclohexamines.
      These substances are problematic as a result of their required storage, handling,
      and record-keeping protocols. A potentially useful alternative sedation protocol
      includes a combination of butorphanol, azaperone, and medetomidine (BAM: 0.43
      mg/kg butorphanol, 0.36 mg/kg azaperone, 0.14 mg/kg medetomidine). One risk of
      wildlife immobilization with any drug combination is hypoxemia. This may be of
      particular importance when using an alpha 2 agonist such as medetomidine because
      of its powerful vasoconstrictive effect. In this prospective study, the BAM
      combination was evaluated for chemical immobilization of white-tailed deer.
      Additionally, selected physiologic parameters associated with BAM immobilization,
      including oxygen saturation via pulse oximetry and arterial blood gas
      measurement, with and without nasal insufflation of oxygen at a relatively low
      flow of 3 L/min, were evaluated. The BAM combination resulted in a predictable
      onset of sedation, with a mean induction time to lateral recumbency of 9.8 +/-
      3.6 min. All deer recovered smoothly within a range of 5-20 min after reversal
      with intramuscular administration of naltrexone, atipamazole, and tolazoline
      (NAT). Clinically relevant decreases in arterial partial pressure of oxygen
      (PaO2) and oxygen saturation (SpO2) were observed in animals not receiving
      supplemental oxygen, while both parameters significantly improved for oxygen
      supplemented deer. Pulse oximetry with this protocol was an unreliable indicator
      of oxygen saturation. In this study, altitude, recumbency, hypoventilation,
      butorphanol- and medetomidine-specific effects, as well as the potential for
      alpha 2 agonist-induced pulmonary changes all may have contributed to the
      development of hypoxemia. Overall, capture of white-tailed deer with the BAM/NAT
      protocol resulted in excellent chemical immobilization and reversal. Because the
      BAM combination caused significant hypoxemia that is unreliably detected by pulse
      oximetry but that may be resolved with nasal oxygen insufflation, routine use of
      oxygen supplementation is recommended.

PMID- 18817018
TI  - Mermithid nematode infection in a colony of blue-winged grasshoppers (Tropidacris
      collaris).
AB  - A die-off occurred in a captive colony of blue-winged grasshoppers (Tropidacris
      collaris) at the Toronto Zoo. One fourth of the colony died within a year due to
      infection with worms initially mistaken for nematomorphs but later identified as
      nematodes belonging to the Mermithidae, genus Mermis. Mortality persisted and the
      grasshopper population dwindled over the following years. Mermithid larvae
      developed in the hemocoel of the insects until they eventually emerged from a
      hollowed-out exoskeleton. Circumstantial evidence suggests that the parasites
      were introduced with raspberry browse that was grown on site and contaminated
      with mermithid eggs.

PMID- 18817019
TI  - Analysis of commercial Entamoeba histolytica ELISA kits for the detection of
      Entamoeba invadens in reptiles.
AB  - Entamoeba invadens is pathogenic in multiple reptile species and has caused
      severe outbreaks in zoos and other facilities worldwide. Infections can be
      difficult to diagnose and to differentiate from other reptilian Entamoeba
      species. The goal of this study was to determine if kits developed to identify
      the human pathogen Entamoeba histolytica could be used to detect E. invadens in
      reptile species at the Maryland Zoo. The E. histolytica II antigen enzyme-linked
      immunosorbent assay and the ProSpecT E. histolytica microplate assay did not
      react with cultured E. invadens controls or with fecal samples from multiple
      reptiles, demonstrating the need for a sensitive and specific test for E.
      invadens.

PMID- 18817020
TI  - Diagnostic challenges in detection of colorectal cancer.

PMID- 18817021
TI  - Correlation of clinical data, anatomical site and disease stage in colorectal
      cancer.
AB  - OBJECTIVE: To evaluate the colorectal cancer clinical data with respect to the
      anatomical location and stage of disease. DESIGN: Retrospective observational
      study. SETTING: Kenyatta National Hospital (KNH), Nairobi, Kenya. SUBJECTS: Two
      hundred and fifty three tumours were categorised as right colonic (RCC), left
      colonic (LCC) and rectal (RC) lesions. The distribution of symptoms (rectal
      bleeding, tenesmus, change in bowel habits, abdominal pain, intestinal
      obstruction, rectal mass), anaemia, transfusion requirement, and the Dukes'
      stages were compared for right colon, left colon and rectal tumours. RESULTS:
      There were 54 RCC, 59 LCC, 140 RC lesions. Patient delay from onset of symptom(s)
      to presentation was a mean of 26.6 +/- 43, 20 +/- 25 and 33.7 +/- 42 weeks for
      right, left and rectal lesions respectively (p = 0.092). The proportion of
      patients presenting with rectal bleeding was 21%, 44% and 79% for RCC, LCC and RC
      lesions, respectively. The prevalence of intestinal obstruction was 14.8%, 27.1%
      and 43.6% in right, left and rectal lesions, respectively. The haemoglobin levels
      were significantly lower for right sided lesions (p = 0.05 for right colon/rectum
      pair; p = 0.059 for right colon/left colon pair). The sites of the lesions had no
      relationship to the stage of disease at presentation. CONCLUSION: In patients
      with colorectal cancer, the duration of symptoms was prolonged irrespective of
      the anatomical sub-sites. Symptoms were evenly distributed across the anatomical
      regions except for bleeding and obstruction which predominated in rectal and left
      colon cancers respectively. This underlines the need for early investigations in
      patients with rectal bleeding, change of bowel habit, intestinal obstruction and
      anaemia.

PMID- 18817022
TI  - Causes of delay in diagnosis of pulmonary tuberculosis in patients attending a
      referral hospital in Western Kenya.
AB  - OBJECTIVE: To determine the length of delays from onset of symptoms to initiation
      of treatment of pulmonary tuberculosis (PTB). DESIGN: Cross-sectional study.
      SETTING: Chest/TB clinic, Moi Teaching and Referral Hospital (MTRH), Eldoret,
      Kenya. SUBJECTS: Newly diagnosed smear positive pulmonary tuberculosis (PTB)
      patients. RESULTS: Two hundred and thirty patients aged between 12 and 80
      (median; 28.5) years were included in the study. They comprised 148 (64.3%,
      median 30 years) males and 82 (35.7%, median 28 years) females. One hundred and
      two (44%) came from urban and 128 (56%) came from rural setting covering a median
      distance of 10 (range 0-100) kilometres and paying Kshs 20 (range 0-200) to
      facility. Cough was the commonest symptom reported by 228 (99.1%) of the patients
      followed by chest pain in 214 (80%). The mean patient delay was 11 +/- 17 weeks
      (range: 1-78 weeks) with no significant difference between males and females, the
      mean system delay was 3 +/- 5 weeks (range: 0-39 weeks). The median patient,
      health systems and total delays were 42, 2, and 44 days respectively for all the
      patients. Marital status, being knowledgeable about TB, distance to clinic and
      where help is sought first had significant effect on patient delay. CONCLUSION:
      Patient delay is the major contributor to delay in diagnosis and initiation of
      treatment of PTB among our patients. Therefore TB control programmes in this
      region must emphasise patient education regarding symptoms of tuberculosis and
      timely health seeking behaviour.

PMID- 18817023
TI  - Bacteriological and clinical evaluation of twelve cases of post-surgical sepsis
      of odontogenic tumours at a referral centre.
AB  - OBJECTIVE: To determine the bacterial aetiology of sepsis occurring following
      surgery of odontogenic tumours and assess the effect of prompt and proper
      antibiotic usage. DESIGN: A prospective study. SETTING: A tertiary referral
      centre in Lagos, Nigeria. SUBJECTS: Twelve patients with odontogenic tumours that
      developed sepsis postoperatively. Eight of the patients were referred from
      private hospitals, the remaining were in-patients who sought for alternative
      medical attention following interruption of health care services at the referral
      centre. INTERVENTION: Adequate review of patient's medical history,
      bacteriological investigations and antibiotic therapy. MAIN OUTCOME MEASURES:
      Bacteriological and clinical cure following antibiotic therapy based on
      susceptibility test results. RESULTS: Two categories of patients were identified;
      those who completed the course of antibiotics prescribed post-surgery and
      patients who failed to conform to antibiotic prescription. Sepsis developed in
      the non-compliance group much earlier than in the group that complied (p<0.001).
      Infections were polybacterial with aerobes accounting for 77.4% (alpha-haemolytic
      streptococci 29.0%, Streptococcus pyogenes 16.1%, Staphylococcus aureus 16.1%,
      diphtheroids 9.7%, Klebsiella pneumoniae 6.5%) and anaerobes 22.6% (Porphyromonas
      gingivalis 9.7%, Peptostreptococcus spp. 6.5%, Prevotella melaninogenica 3.2%,
      Clostridium perfringens 3.2%). Mixed aerobic and anaerobic aetiology occurred
      more in osteosarcoma and fibrosarcoma. Clostridium perfringens was isolated from
      a case of osteosarcoma with necrotic tissues. The anaerobic bacteria were 100%
      sensitive to metronidazole, ciprofloxacin and augmentin, 65-85% sensitivity to
      ampicloxacillin, amoxicillin and erythromycin. Over 92% of the streptococci were
      sensitive to the beta-Lactams contrast low susceptibility with S. aureus and K.
      pneumoniae. CONCLUSION: Interruption of healthcare service was the sole factor
      identified in the development of sepsis as the patients could not be monitored to
      ensure compliance to prescription.

PMID- 18817024
TI  - Birth preparedness among antenatal clients.
AB  - OBJECTIVE: To evaluate birth preparedness and complication readiness among
      antenatal care clients. DESIGN: A descriptive cross- sectional study. SETTING:
      Antenatal care clinic at Kenyatta National Hospital, Nairobi, Kenya. SUBJECTS:
      Three hundred and ninety four women attending antenatal care at Kenyatta National
      hospital were interviewed using a pre-tested questionnaire between May 2006 and
      August 2006. Clients who were above 32 weeks gestation and had attended the
      clinic more than twice were recruited. Systematic sampling was used to select the
      study participants with every third client being interviewed. MAIN OUTCOME
      MEASURES: Health education on birth preparedness, knowledge of danger signs,
      preparations for delivery and emergencies. RESULTS: Over 60% of the respondents
      were counselled by health workers on various elements of birth preparedness.
      Eighty seven point three per cent of the respondents were aware of their expected
      date of delivery, 84.3% had set aside funds for transport to hospital during
      labour while 62.9% had funds for emergencies. Sixty seven per cent of the
      respondents knew at least one danger sign in pregnancy while only 6.9% knew of
      three or more danger signs. One hundred and nine per cent of the respondents did
      not have a clear plan of what to do in case of an obstetric emergency. Level of
      education positively influenced birth preparedness. CONCLUSIONS: Education and
      counselling on different aspects of birth preparedness was not provided to all
      clients. Respondents knowledge of danger signs in pregnancy was low. Many
      respondents did not know about birth preparedness and had no plans for
      emergencies.

PMID- 18817025
TI  - Environmental and occupational exposure to lead.
AB  - OBJECTIVE: To determine the status of environmental and occupational lead
      exposure in selected areas in Nairobi, Kenya. DESIGN: Cross sectional study.
      SETTING: Kariobangi North, Babadogo, Waithaka and Pumwani for assessment of
      environmental exposure to lead (Pb) and Ziwani Jua Kali works for assessment of
      occupational lead exposure. Olkalou in Nyandarua District was the covariate study
      area. SUBJECTS: Three hundred and eight children and adults participated.
      RESULTS: Blood lead levels (BLLs) obtained for the entire sample (n = 308) ranged
      from 0.4 to 65 microg/dl of blood. One hundred and sixty nine (55%) of the total
      sample had levels equal to or below 4.9 microg/dl, while 62 (20%) of the sample
      had levels ranging from 5.0 to 9.9 microg/dl. Blood lead levels above 10
      microg/dl were recorded in 77 (25%) of the total sample. Within Nairobi, 32
      (15.3%) of the study subjects in areas meant for assessment of environmental lead
      exposure had levels above the WHO/CDC action levels of 10 microg/dl of blood. The
      mean BLL for the occupationally exposed (Ziwani Jua kali) was 22.6 +/- 13.4
      microg/dl. Among the workers, 89% had BLLs above 10 microg/dl. In general, 15% of
      the entire sample (for both environmental and occupational groups) in Nairobi had
      BLLs above 15 microg/dl. The covariate group at Olkalou had a mean BLL of 1.3 +/-
      0.9 microg/dl. CONCLUSION: The prevalence of environmental lead exposure to the
      general public is high in Nairobi compared to Olkalou where non exposure was
      reported. Occupational lead exposure has been identified to be at alarming levels
      and urgent intervention measures are recommended.

PMID- 18817026
TI  - HIV/AIDS: the first 25 years--a view from Nairobi.
AB  - HIV infections are zoonoses occurring in communities that hunt chimpanzees (HIV
      1) and sooty mangabeys (HIV 2) in the forests of equatorial and West Africa
      respectively. Most cross species transmission to man probably fizzles out, but
      the transmission of HIV 1 type M around 1930 eventually resulted in a pandemic
      that has spread around the world. HIV 2 types A and B have caused epidemics in
      West Africa. HIV infections are characterised by three phases (i) an initial,
      primary infective phase with rising viraemia, asymptomatic and silent, lasting
      for some 10 weeks, (ii) a long quiescent phase with the viraemia and illness
      mostly held in check by the immune response and lasting some 10 years in HIV 1
      and 20 years or so in HIV 2 and (iii) a terminal third phase lasting some 10
      months with rising viraemia, falling CD4 levels and multiple opportunistic
      infections recognised in a community by the onset of a florid AIDS epidemic. The
      silent primary epidemic reached Nairobi around 1980, with the florid secondary
      AIDS epidemic peaking here around 1992 and overwhelming the hospitals and other
      health services. The introduction of highly active antiretroviral therapy (HAART)
      has dramatically improved the prognosis for individual patients with AIDS, but it
      has been education and a changing attitude to condoms that has led to a
      progressive fall in incidence, so that the worst of the epidemic may now be over.
      Modifying the immunological response during the quiescent phase with the hope of
      prolonging this phase indefinitely may be the way forward for those who are
      already infected. Steroids have been shown to have a possible role here rather
      than anti-retroviral drugs (ARVs) which are not curative and prone to the
      development of drug resistance. Limited personal experience suggests that
      steroids may also have a role in salvaging critically ill AIDS patients, who need
      to be treated as emergencies. With an educated public and attention to
      alternative routes of infection such as blood transfusion, the epidemic should be
      increasingly contained during the next 25 years, and may even fizzle out.

PMID- 18817027
TI  - Successful pregnancy outcome following laparoscopic myomectomy: case report.
AB  - Laparoscopic myomectomy is now widely used as an alternative to laparotomy in the
      management of symptomatic uterine fibroids. The advantages of this minimal access
      approach outweigh those of the open techniques. The pregnancy outcomes between
      the two methods have been studied and are comparable, but there still exists a
      lot of scepticism locally concerning this. It is against this background that we
      present a 31 year old nulliparous lady who had a two year history of primary
      infertility secondary to multiple uterine fibroids, the largest being fundal and
      measuring 6.6cm. She underwent a successful laparoscopic myomectomy in November,
      2006 and conceived spontaneously in February 2007. Her antenatal follow up was
      uneventful. She delivered a live male, 2,650 grams by Caesarean section in
      October, 2007 and had an unremarkable peuperium. With the availability of proper
      equipment, instruments, and adequately developing skills, laparoscopic myomectomy
      is feasible locally and with proper patient selection could result in favourable
      outcome as it is elsewhere.

PMID- 18817028
TI  - Primary cerebral angitis of the central nervous system: case report.
AB  - We report a case of a 28 year old female who presented with variedly progressive
      stroke like illness and raised intracranial pressure. Brain MRI scans revealed
      pericallosal and periventricular hyperintensities with oedema. Various
      medications like intravenous immunoglobulin, antibiotics, acyclovir, methyl
      prednisolone and management for raised intracranial pressure were instituted. She
      rapidly deteroriated and died on tenth hospital day. Only at autopsy was the
      diagnosis of primary angitis of central nervous system established.

PMID- 18817029
TI  - [The time-dependent changes of phospho-JNK expression during the skin incised
      wound healing in mice].
AB  - OBJECTIVE: To investigate the changes of phospho-JNK (p-JNK) during the incised
      wound healing of the skin in mice and to explore the rule of the time-dependent
      change of p-JNK in wound age determination. METHODS: The changes of p-JNK
      expression in incised skin wound were detected by immunohistochemistry and
      Western blot. RESULTS: There was a minimal baseline staining of p-JNK in control
      mouse skin. Changes of p-JNK expression were mainly detectable in neutrophils in
      the wound specimens from 3 hours to 12 hours after injury. Afterwards, the p-JNK
      positive cells were mostly mononuclear cells and fibroblasts between post-injury
      day 1 and day 5, whereas the p-JNK positive cells were mostly fibroblasts between
      post-injury day 7 and day 14. Morphometrically, the ratio of the p-JNK positive
      cells to the total increased gradually in the wound specimens from 3 hours to day
      1, and maximized at day 1 with a slight decrease from post-injury day 3 to day 5.
      The ratio showed a second peak in the specimens of day 7, and then decreased
      gradually from post-injury day 10 to day 14. The changes of p-JNK expression were
      observed throughout the wound healing stages by Western blot as well, with a peak
      expression occurring between 12 hour and day 3 after injury. CONCLUSION: p-JNK
      may play a pivotal role in inducing apoptosis of neutrophils, mononuclear cells,
      and fibroblasts during skin wound healing and meanwhile, p-JNK may be a
      potentially useful marker for wound age determination.

PMID- 18817030
TI  - [The expressions of HSP 70 mRNA and c-fos mRNA in the skeletal muscle and cardiac
      muscle of rabbits by electrocuted].
AB  - OBJECTIVE: To study the changes of HSP 70 mRNA and c-fos mRNA expression and to
      find a method to differentiate antemortem from postmortem electrocution. METHODS:
      Fifteen New Zealand rabbits were randomly divided into three groups, the
      antemortem electrocution group, the postmortem electrocution group, and the
      control group. Each group consists of five rabbits. The levels of HSP 70 mRNA and
      c-fos mRNA in skeletal muscle and cardiac muscle were examined with quantitative
      fluorescent RT-PCR. RESULTS: The levels of HSP 70 mRNA and c-fos mRNA in the
      antemortem electrocution group increased significantly (P<0.05), compared with
      that of the postmortem electrocution group. CONCLUSION: The changes of HSP 70
      mRNA and c-fos mRNA expression in skeletal muscle and cardiac muscle can be used
      as an indicator to distinguish antemortem from postmortem electrocution.

PMID- 18817031
TI  - [Comparison of thresholds acquired with ASSR and PTA in normal-hearing subjects].
AB  - OBJECTIVE: To provide new objective technology in evaluating hearing loss for
      forensic expert by comparing the thresholds acquired with auditory steady-state
      responses (ASSR) and pure tone audiometry (PTA) in our laboratory. METHODS:
      Twenty-seven subjects with normal hearing (54 ears, 18-28 years) were tested with
      PTA and ASSR at 500, 1000, 2000 and 4000 Hz. Paired t-test analysis was performed
      on threshold of ASSR and PTA at difference frequency (500, 1000, 2000 and 4000
      Hz). RESULTS: At each frequency (500, 1000, 2000 and 4000 Hz), the thresholds
      acquired with ASSR were higher than those acquired with PTA (P<0.05). The mean
      difference of each frequency were (22.04+/-5.79) dB (500 Hz), (11.02+/-5.44) dB
      (1000 Hz), (12.59+/-5.89) dB (2000 Hz) and (17.78+/-7.25) dB (4000 Hz). The mean
      difference between the system automatically adjusted threshold of ASSR and PTA
      were (-3.96+/-5.79) dB at 500 Hz, (0.02+/-5.44) dB at 1000 Hz, (-0.41+/-5.89) dB
      at 2000 Hz, and(-1.25+/-7.25) dB at 4000 Hz. CONCLUSION: At each frequency (500,
      1000, 2000 and 4000 Hz), the thresholds acquired with ASSR were higher than those
      acquired with PTA. The mean difference is 16.9 dB. As an objective and mature
      method, ASSR could be used in evaluation of hearing-loss degree for forensic
      expert. But adjusted threshold value should be established when ASSR is used to
      estimate hearing threshold in each laboratory.

PMID- 18817032
TI  - [Assessment of skeletal age in Chinese male adolescents].
AB  - OBJECTIVE: To develop medicolegal expertise standard to assess skeletal age of
      Chinese male adolescents by joint X-ray. METHODS: Radiographs of male adolescent
      aged 11 to 20 years were obtained in Southern, Central, and Eastern China. The
      bone development process were graded according to morphology characteristics in
      radiograph based on the appearance of secondary ossification centers and the
      arrest of epiphysises. All statistical analysis was carried out with SPSS and
      SAS. RESULTS: Most indexes were correlated to age. Optimization multiple
      regression equation was created to estimate age of adolescent. Discriminatory
      equations were established to distinguish the age of 14, 16 or 18 years.
      CONCLUSION: More anatomical site evaluation and more index application can
      improve the accuracy rate. The methods can be used in age determination by
      skeleton in Chinese male adolescents.

PMID- 18817033
TI  - [An examination of the self-reported scale of brief psychopathological symptoms
      to detect malingering in forensic psychiatric subjects].
AB  - OBJECTIVE: To examine the self-reported scale of brief psychopathological
      symptoms (SBPS) to detect malingering in forensic psychiatric cases. METHODS: Two
      hundred and six cases with different types of psychiatric problems were tested by
      SBPS. All cases were separately evaluated by two experts. RESULTS: About 34.5%
      cases (71/206) were classified as malingering by the cut-off 13 scores of SBPS.
      Compared with expert's evaluation, SBPS showed a false negative rate of 19.8% and
      a false positive rate of 1.7%, respectively, with a total accuracy rate of 90.8%.
      Cases involved in compensations including working injury and traffic accidence
      showed the highest rate of malingering (51%). CONCLUSION: SBPS is useful for
      detecting malingering psychopathological symptoms.

PMID- 18817034
TI  - [Multiple amplification of 16S rRNA gene and Cytb gene in mitochondrial DNA for
      species identification].
AB  - OBJECTIVE: To establish a fluorescent multiple amplification system of 16S rRNA
      and Cytb genes located in mitochondrial DNA for species identification. METHODS:
      A pair of primers of 16S rRNA gene and Cytb gene of the mitochondrial DNA was
      designed with the software Primer 5.0 to construct a multiple amplification
      system. The amplified products from human and five species of animals, including
      cattle, pig, dog, chicken and grass carp were analyzed by 310 Genetic Analyzer.
      RESULTS: The amplified products of these samples showed two peaks. The common one
      was 358bp and the specific one different in unique species was between 231bp and
      256bp. CONCLUSION: The multiplex amplification system can exactly distinguish the
      species of human from five common animals.

PMID- 18817035
TI  - [DNA polymorphism detection of Papaver somniferum L using fluorescent amplified
      fragment length polymorphism].
AB  - OBJECTIVE: To detect DNA polymorphism of Papaver somniferum L using fluorescent
      Amplified Fragment Length Polymorphism. METHODS: Genomic DNA was isolated using
      the AxyPrep DNA Kit, double-digested by two restrictional endonucleases (Eco RI
      and Mse I) and ligated to oligonucleotide adapters. After Pre-amplification and
      selective amplification, the DNA fragments were separated by capillary
      electrophoresis using the CEQ8000 DNA Fragment Analyzer. RESULTS: More than 20
      fragments of highly polymorphic products were obtained by 8 pairs of primer from
      64 selective amplifying primer pairs. CONCLUSION: The fluorescent AFLP technique
      can be used to detect the DNA polymorphism of Papaver somniferum.

PMID- 18817036
TI  - [The relation of blood alcohol concentration and neurobehavioral functions after
      drinking].
AB  - OBJECTIVE: To research the relation between blood alcohol concentration (BAC) and
      neurobehavioral function after drinking. METHODS: The neurobehavioral ability
      index (NAI) of 233 volunteers were measured with computer-administered
      neurobehavioral evaluation system-Chinese3 (NES-C3). RESULTS: The NAI of simple
      visual reaction time and mental arithmetic declined when BAC was more than 0.157
      mg/mL, the NAI of benton visual retention, length discrimination and digit cancel
      declined significantly when BAC was more than 0.204 mg/mL. CONCLUSION: The
      neurobehavioral function declined significantly when BAC increased and recovered
      gradually when BAC declined due to the elimination of alcohol in blood.

PMID- 18817037
TI  - [Simultaneous analyses of cocaine and its metabolite benzoylecgonine in urine by
      LC-MS/MS].
AB  - OBJECTIVE: To establish a liquid chromatography-tandem mass spectrometry (LC
      MS/MS) method for the simultaneous analysis of cocaine (COC) and its metabolite
      benzoylecgonine(BZE) in urine samples. METHODS: A single dose of COC (10 mg/kg)
      was injected intraperitoneally into guinea pigs and urine samples were collected
      for 7 days. The urine samples were extracted by auto solid phase extraction
      (SPE), separated by the Allure PFP propyl column with a mobile phase consisting
      of methanol and 20 mmol/L ammonium acetate buffer [0.1% formic acid (80:20,
      V/V)], and then analyzed by LC-MS/MS. Multiple reaction monitoring (MRM) mode was
      used to analyze COC (m/z 304.2-->182.3, m/z 304.2-->150.1) and BZE (m/z 290.2-
      >168.3, m/z 290.2-->105.0). RESULTS: COC and BZE showed a fairly good linearity
      over the range of 2.0-100 ng/mL (r=0.9995). The detection limit was 0.5 ng/mL.
      The recovery rate was greater than 90% and the deviation of intra- and inter-day
      precision was less than 6%. BZE was the major target detected in urine samples,
      and its detection window was longer than COC. CONCLUSION: This newly developed
      method shows high sensitivity and selectivity, and is suitable for the
      simultaneous analysis of cocaine and benzoylecgonine in urine samples.

PMID- 18817038
TI  - [A forensic pathological study of eighty-two cases of adrenal hemorrhage].
AB  - OBJECTIVE: To analyze the relationship between adrenal hemorrhage and the cause
      of death, age and gender. METHODS: Eighty-two cases of adrenal hemorrhage were
      statistically analyzed. RESULTS: Adrenal hemorrhage occurred mostly in cases of
      sudden death, infection, trauma and asphyxia. Male had more chance than female to
      have adrenal hemorrhage. Adrenal hemorrhage caused by sudden death, trauma and
      poisoning was more frequently seen in young adults, whereas adrenal hemorrhage in
      children as well as in fetus and newborns was often caused by infection as well
      as sudden death and asphyxia respectively. Adrenal hemorrhage caused by sudden
      death and asphyxia was mainly located in medulla, while the infection usually
      induced hemorrhage in cortex. Adrenal hemorrhage caused by trauma showed an equal
      opportunity in either the cortex or medulla. CONCLUSION: Our data indicate that
      adrenal hemorrhage might provide some clues in searching for the cause of death.

PMID- 18817039
TI  - [Advances in research of diagnosis of drowning in forensic medicine].
AB  - The current macroscopical and microscopical signs in the fresh drowning victim
      are non-specific. Moreover, putrefaction will vanish these autopsy findings quite
      rapidly. The study of additional detecting methods to diagnose drowning has
      become one of the hottest topics in forensic medicine. This article reviewed
      several methods commonly used in the determination of drowning in forensic
      practice. The advantages and disadvantages of various methods were also
      discussed.

PMID- 18817040
TI  - [Electrophysiological examination of peripheral nerve injury and its significance
      in forensic medicine].
AB  - Assessment of peripheral nerve injury is a common task in forensic practice. As
      an objective assistance of inspection, electrophysiological examination is
      significant in the evaluation of peripheral nerve function after injury. There
      are currently several methods of electrophysiological examination, including I-T
      curve, EMG, NCV and SEP. Because electrophysiological examination can assess the
      injury and regeneration of peripheral nerve injury at different times, it is
      valuable to estimate prognosis of peripheral nerve injury in forensic medicine.
      Besides the electrophysiological examination, evaluation of the peripheral nerve
      injury needs to combine other clinical manifestations to provide an accurate
      appraisal.

PMID- 18817041
TI  - [The relationship between SNP of cholecystokinin gene and certain mental status
      and its forensic significance].
AB  - Cholecystokinin (CCK) is a brain-gut peptide with broad biological activities. It
      is one of the main regulating hormones in the digestive system, and it plays an
      important physiological role in the central and peripheral nervous system as a
      neurotransmitter or a neuromodulator. Recently, many reports have demonstrated
      that there were a number of SNPs on CCK gene, of which -45C/T and -196G/A showed
      certain correlation with a variety of psychiatric states such as schizophrenia,
      depressive disorder, suicidal behavior, Parkinson's disease, etc. These SNPs may
      be used in paternity testing and personal identification. In addition, it may
      also become one of the auxiliary indicators in some special cases of forensic
      pathology.

PMID- 18817042
TI  - [Detection of malingering post-traumatic stress disorder].
AB  - Assessment of post-traumatic stress disorder is a frequently encountered problem
      in forensic practices. Detection of malingering has become a focus in these
      assessments. While it is a difficult task due to kinds of traumatic events,
      complex clinical symptoms, subjective medical information, and presence of
      diverse psychotic disorders. The clinical traits, detecting methods and testing
      instruments of PTSD malingering were reviewed so as to help practical management
      and assessment.

PMID- 18817043
TI  - [Tramadol intoxication and its toxicological effect].
AB  - Tramadol is a centrally acting analgesic with a dual mode of action. Its
      analgesic efficacy is attributed to its partial affinity for the mu-opiate
      receptor and its inhibition of norepinephrine and serotonin reuptake. Acting in a
      synergistic manner and being more efficacious, tramadol is used worldwide for the
      treatment of moderate to severe acute or chronic pain. Abuse and dependence of
      tramadol as well as tramadol-related deaths have been increasingly reported,
      either ingested alone or taken in combination with other potentially interacting
      drugs. The possible toxic effect of tramadol was reviewed from aspects of its
      analgesic mechanisms, adverse effect, dependence, and abuse.

PMID- 18817044
TI  - [Discussion on medical malpractice in traumatic injury].
AB  - By reviewing five medical tangle cases after traumatic injury, the characters of
      these cases and the cause of medical malpractice had been discussed. After the
      analysis of the responsibility to the death caused by traumatic injury and
      medical malpractice, the assessment principle of cooperative competition of
      causes and degree of participation had been introduced. Meanwhile, it is believed
      that if comprehensive postmortem examination and pathologic examination were
      carried out to verify the death cause at first, they would play more important
      role in the appraisal of medical tangle cases after traumatic injury.

PMID- 18817045
TI  - The relationship between gallstone disease and gall bladder volume.
AB  - BACKGROUND: The role of a large gallbladder volume with regards to a
      predisposition to gallstones is unknown. It is likely that an increase in
      gallbladder volume could result in impaired gallbladder motility and bile stasis
      which may encourage gallstone formation. This study is therefore to determine the
      relationship between the presence of gallstone disease and gall bladder volume.
      METHODOLOGY: One hundred type 2 diabetic patients and 100 age and sex-matched
      controls underwent real time ultrasonography to determine the relationship
      between the presence of gallstone disease and gallbladder volume. Their
      demographic characteristics were recorded and compared. The ultrasound
      examinations was done in the morning following an overnight fast (to prevent gall
      bladder contraction) without sedation. Longitudinal and transverse scans of the
      right upper quadrant was done in both the supine and left lateral positions The
      gallbladder volume was measured. RESULT: The mean gallbladder volume in diabetic
      patients with gallstone disease 28.4 +/- 18.6 ml was higher than in those without
      gallstone disease 27.4 +/- 14.8 ml p = 0.844. The mean gallbladder volume in the
      controls with gallstone disease 26.5 +/- 14.7 ml was also higher than in those
      without gallstone disease 24.1 +/- 12.7 ml p = 0.189. CONCLUSION: The fasting
      gallbladder volume tended to be larger in patients with gallstones (i.e. both
      diabetic patients and controls).

PMID- 18817046
TI  - Hepatitis C virus infection in Nigerians with diabetes mellitus.
AB  - BACKGROUND/AIMS: Studies from mainly Caucasian populations have shown
      epidemiological evidence of an association between diabetes mellitus and
      Hepatitis C virus (HCV) infection. The aim of this study was to determine whether
      any such association exists in a blackAfrican population with diabetes mellitus.
      METHOD: This was a cross sectional study of consecutive diabetic patients seen at
      the diabetes clinic of the University of Nigeria Teaching Hospital Enugu, Nigeria
      between September 1, 2004 and April 30, 2005. Patients who underwent upper
      gastrointestinal endoscopy during the same period for dyspeptic symptoms were
      used as controls after matching for age and sex. Structured questionnaire on risk
      factors for HCV infection was administered to the participants. Blood test for
      HCV antibodies was carried out on the diabetic patients as well as the control
      subjects. RESULTS: Out of 191 diabetic patients, 27(14.1%) were HCV antibody
      positive compared to the control group in which 5 out of 134 (3.7%) subjects had
      HCV antibodies (p = 0.0046). CONCLUSION: Hepatitis C virus infection is more
      common in Nigerian patients with diabetes mellitus than in control subjects. The
      nature of the association between diabetes mellitus and HCV infection remains to
      be elucidated.

PMID- 18817047
TI  - Reasons for preference of delivery in spiritual church-based clinics by women of
      south-south Nigeria.
AB  - OBJECTIVES: To investigate the various reasons for patronizing the spiritual
      church-based clinics by women from South-South Nigeria. DESIGN: Forty seven
      spiritual church-based clinics were studied between 1st February 2003 and 31st
      July 2003. SETTING: Forty seven spiritual church-based clinics in both Akwa Ibom
      and Cross River State in South-South Nigeria. PATIENTS: Two thousand and sixty
      three pregnant women who were regular attendants of the spiritual church-based
      clinics. RESULTS: Various reasons for preferring church delivery included:
      Spiritual protection against satanic attacks and safe delivery in 975 (36.8%)
      lack of funds in 629 (30.5%), harsh attitude of health workers in 249 (12.1%),
      convenience in 212 (10.3%), faith in God and previous delivery in church 83
      (4.0%) each help and good care guaranteed in 48 (2.35). CONCLUSION: It is
      suggested that the spiritual churches with interest in obstetric care establish
      properly staffed and well equipped health clinics as an annex to the church.

PMID- 18817048
TI  - Early postnatal growth of preterm low birth weight, appropriately-sized infants.
AB  - BACKGROUND: Postnatal growth monitoring is useful in assessing the health
      ofpreterm babies but their growth patterns have not been sufficiently studied in
      Africans. AIM: To describe the growth achievements ofpreterm, low birth weight,
      appropriately-sized, Nigerian infants. STUDY DESIGN: The subjects were
      prospectively recruited from two centers Olabisi Onabanjo University Teaching
      Hospital (January 1994 to June 1995) and Havana Specialist Hospital (June 1995 to
      June 1997). The weight, length and occipito-frontal circumference of 89 preterm,
      low birth weight, appropriate-for-dates infants were monitored from birth until
      53 post-conceptual weeks. Growth velocities were compared with 46 term infants.
      RESULTS: Initial weight loss, age at regaining birth weight and growth rate in
      the early postnatal weeks were inversely related to gestational age. Subsequent
      weight gain was directly related to gestational age. Between birth and 40 weeks
      post conception, growth rates for different gestational age groups were 129 to
      207 g/week (weight), 0.78 to 0.93 cm/week (length) and 0.62 to 0.65 cm/week (head
      circumference). After 40 weeks, the corresponding rates were 188 to 238 g/week,
      0.86 to 0.96 cm week and 0.48 to 0.50 cm/week, respectively. Head growth
      demonstrated a faster catch-up than weight and body length in that order. The
      observed growth rates were slower in some respects than Caucasian figures but
      faster than reported for the Japanese. CONCLUSION: Study subjects had growth
      patterns within previously defined ranges. The better profile of western babies
      is probably related to better infrastructure while the advantage over Asian
      babies is probably racial.

PMID- 18817049
TI  - Changing trends in maternal mortality in a developing country.
AB  - OBJECTIVE: To have a 5-year review of the maternal mortality ratio in the largest
      centrally located Mission hospital in Benin City where a large proportion of
      women deliver yearly. METHOD: This was a 5-year (January 1, 1996 through December
      31, 2000) review of the causes of maternal mortality at the Saint Philomena
      Catholic Hospital, Benin City. The case notes of those that suffered maternal
      mortality were retrieved and thoroughly perused. Information on all cases of
      maternal mortality were extracted from the patients' case-notes; the labour ward
      Registers; the antenatal, postnatal, the female ward and the theatre registers.
      The midwifery/nurses' reports were also examined. The duplicate copies of the
      death certificates were examined and the necessary information was also
      extracted. The total deliveries for the period were extracted from the delivery
      registers. RESULTS: There were 7055 women who gave birth during the 5-year
      period. There were 32 maternal deaths; Maternal Mortality Ratio (MMR) of 454/
      100,000 live births. Unbooked emergencies accounted for 68.7% of all deaths, and
      were more than doubled the booked women. The MMR increased progressively from 325
      in 1996 to peak at 765 in 1999 (P < 0.0001) with an insignificant drop in 1998 (P
      > 0.06). It was lowest in 2000 (241) (P < 0.0001). Paradoxically, as the number
      of deliveries decreased progressively from 1530 in 1996 to 1247 in 2000, the MMR
      increased progressively from 327 in 1996 to 675 in 1999. There were no postmortem
      examinations and no coroner's inquests. More than 76% of the women spent 48 hours
      or less from time of admission to death and majority of them were of low parity.
      Nulliparity was 37.5%. The mean parity was one. Young women 20-39 years old
      accounted for 81.3% with 9.4% teenage deaths due to illegally induced abortions.
      Eclampsia (34.4%), hemorrhage (25.0%), Infections (18.8%) and abortions 12.5%)
      were the four leading causes of death. Puerperal deaths were 56.3%. Five short
      case scenarios were presented to highlight the tortuous pathway the women passed
      to end in maternal mortality. CONCLUSION: The MMR ratio was still unacceptably
      high. The causative factors were largely preventable. The puerperium was the most
      dangerous period. Women empowerment, free or highly subsidized universal
      antenatal care services, and provision of adequate emergency obstetric services
      with effective contraceptive backup is suggested. Re-orientation of care givers
      and community leaders to enhance awareness and early recognition of the danger
      signs and risk factors associated with pre-eclampsia and eclampsia with prompt
      and adequate management or referral is emphasized.

PMID- 18817050
TI  - Adult nephrectomy: our experience at Ile-Ife.
AB  - OBJECTIVES: To determine indications for adult nephrectomy in our community and
      the outcome of the procedure in our Institution. MATERIALS AND METHOD: Records of
      adult patients scheduled for nephrectomy at Obafemi Awolowo University Teaching
      Hospital from January 1993 to December 2004 were reviewed. Information extracted
      and analysed included age of patient, sex, presentation, investigations,
      indication, type and outcome of nephrectomy, histopathology result and duration
      of follow up. RESULTS: During the period, thirty adult patients mean age 42.73
      yrs (range 16-80 yrs, M:F = 2:1) were scheduled for nephrectomy. Indications
      included suspicion of malignancy in 19 (63.3%) patients, protracted loin pain in
      non-functioning kidney in 2 (6.7%), uncontrollable bleeding in a patient with
      bilateral polycystic kidney (3.3%), pyonephrosis with septicaemia in a patient
      (3.3%), kidney injury (grade 5) in 2(6.7%) and kidney donation for
      transplantation in 3(10%). Ultrasound and intravenous urography were useful in
      the patients' evaluation. Twenty-seven (90%) patients were operated upon, but
      only 25 (83.3%) had nephrectomy. Sixteen (53.3%) had radical nephrectomy, 5
      (16.7%) had simple nephrectomy, 3 (10%) had nephro-ureterectomy, and one (3.3%)
      had partial nephrectomy. Major surgical complications included wound sepsis
      (18.5%) and primary haemorrhage (7.4%). The overall morbidity and mortality rates
      were 7.4% and 3.7% respectively. Postuninephrectomy, patients' renal function
      remained stable after an average of 34.05 months follow-up. CONCLUSION: Renal
      tumours constitute the main indication for adult nephrectomy in our community.
      Kidney injury, kidney donation, and pyonephrosis are relatively uncommon
      indications. Open nephrectomy, which remains our local practice, is safe and
      unilateral nephrectomy is compatible with normal life.

PMID- 18817051
TI  - Improving the safety of room air pneumoperitoneum for diagnostic laparoscopy.
AB  - BACKGROUND: Laparoscopic examination is a useful investigation in the evaluation
      of infertile women. To perform this test, pneumoperitoneum is required to distend
      the abdomen, improve visibility and displace the intestines out of the pelvis.
      Several gases have been used to achieve this purpose including Nitrous Oxide
      (N2O), Carbondioxide (CO2), Helium, Xenon andAir. STUDY DESIGN AND METHOD: This
      was a prospective study in a private fertility centre in Nnewi, Nigeria aimed at
      reducing the morbidities inherent in the use Room Air pneumoperitoneum for
      diagnostic laparoscopy. This was sequel to an earlier study, which revealed that
      women who had Room Air pneumoperitoneum had a higher port wound infection rate,
      abdominal discomfort (feeling of retained gas in the abdomen) and shoulder pain
      with resultant delayed return to normal activity than women who had Co2
      pneumoperitoneum. RESULTS: This study demonstrated that the use of soda lime to
      purify the Room Air and a low pressure suction pump to evacuate the air after the
      procedure significantly reduced the wound infection rate and virtually eliminated
      the abdominal discomfort and shoulder pain associated with Room Air
      pneumoperitoneum. This was followed by early return to normal activity.
      CONCLUSION: Therefore, use of Room Air for pneumoperitoneum is safe and
      affordable. It is recommended for low resource settings.

PMID- 18817052
TI  - Placenta praevia at the Obafemi Awolowo University Teaching Hospitals Complex,
      Ile-Ife. A ten year analysis.
AB  - CONTEXT: Placenta preavia is one of the obstetric emergencies associated with
      maternal mortality and morbidity. It is also a major cause ofprematurity. With
      prompt and appropriate management the complication can be drastically reduced.
      OBJECTIVE: The objective of this study is to document the pattern of
      presentation, mode of management and the outcome of the management of placenta
      praevia at Obafemi Awolowo Teaching Hospitals Complex (I.H.U.), Ile-Ife between
      January, 1996 to December, 2005. The outcome will help in identifying the women
      at risk and offer suggestions to reduce the associated complications. MATERIALS
      AND METHODS: The study involved a ten-year retrospective analysis of the data
      collected from the case records of all the cases diagnosed as having placenta
      praevia during the period under review. RESULTS: During this period there were
      7515 deliveries and a total of 128 cases of placenta praevia giving an incidence
      of 1.65% i.e. 3 in 200 births. Majority (58.2%) of patients with placenta praevia
      were unbooked and 77.4% of them were multiparous. Only 20.2% were accessible for
      diagnosis by ultrasound scanning, while 25.8% of them were delivered before 36
      weeks of gestation. The perinatal mortality rate was 177 per 1000 births.
      CONCLUSION: Placenta praevia is still a major cause of obstetric morbidity and
      mortality. The diagnosis can be made with routine ultrasound scanning which then
      allows patient identification and institution of appropriate and comprehensive
      treatment aimed at minimizing complications. The role of good referral system, 24
      hours blood banking services and facilities for caesarean section and adequate
      neonatal backup in preventing morbidity and mortality associated with the
      condition can not be over emphasized.

PMID- 18817053
TI  - Hydatidiform mole in gombe: a five year Histopathological review.
AB  - OBJECTIVE: The purpose of this study is to do a histopathological review of all
      cases ofhydatidiform moles seen in pathology department of Federal Medical
      Centre, Gombe between June 2000 and May 2005. METHODS: All the relevant request
      forms, slides and paraffin embedded tissue blocks were retrieved. The slides
      stained with routine Haematoxylin and Eosin were then reviewed. RESULTS: Thirty
      four cases of hydatidiform moles were studied and these formed 7.5% of all
      products of conception seen during the review period. There were 18 cases of
      complete hydatidiform mole and 16 cases of partial hydatidiform mole. No invasive
      or tubal mole was seen during this period. The frequency of hydatidiform moles
      was 1 in 166 delivaries. The age range for all the molar pregnancies was 15-44
      years with vaginal bleeding as their leading mode of presentation between 11-18
      weeks ofgestatation. CONCLUSION: Molar gestation was found to be a common
      gynaecological problem in Gombe affecting women mainly in their third decade of
      life.

PMID- 18817054
TI  - Overview of contraceptive use in Jos University Teaching Hospital, north central
      Nigeria.
AB  - BACKGROUND: Modern contraceptive methods accepted by 17,846 new clients in Jos
      University Teaching Hospital, a tertiary health institution, over two decades are
      presented. METHODS: This was a review of the contraceptive trend in new clients
      who used the various methods of contraception over an 18-year period, 1985-2002.
      RESULTS: The accepted methods were the intrauterine device (26.1%), oral
      contraceptive pills (23.5%), female sterilization (21.7%), the Injectable
      (14.2%), male condom (9.5%), Norplant implants (4.9%) and vasectomy (0.1%).
      Reversible methods were used by 78.2% and the permanent forms by 21.8%. The women
      were the acceptors of the methods in 90.5%, while men contributed only 9.5% of
      the new acceptors. Ten men only had vasectomy over the period of study.
      CONCLUSION: The Intrauterine device was the leading method of contraception
      accepted by the women and male vasectomy was the least accepted by men. There is
      the need for increased male involvement in contraceptive issues.

PMID- 18817055
TI  - Health effects of night shift duty on nurses in a university teaching hospital in
      Benin City, Nigeria.
AB  - OBJECTIVE: This study is aimed at identifying the effects of night shift duty on
      the health and wellbeing of nurses in order to make recommendations on ways of
      ameliorating them. METHODS: The study was ofa cross sectional descriptive type
      using a total sample of nurses in the hospital. Data collection was by means of a
      semi-structured self-administered questionnaire and the analysis by the computer
      Programme for Epidemiologists (PEPI). RESULTS: The response rate was 79.3% with a
      total of 211 (68.1%) having one or more health complaints, which included muscle
      ache and pains (58.7%), frequent headaches (21.9%), lack of concentration (21.3%)
      and a negative effect on social life (66.1%). The younger nurses disliked night
      shift more than the older ones (2 = 57.5, df=6, p = 0.000) and 57.7% felt they
      were less productive during night shift. The shorter the period of sleep after
      the night shift, the lesser the level of productivity and the more the
      manifestation of health symptoms (2 = 45.5, df = 4, p = 0.000 and 2 = 29.0, df =
      2, p = 0.000 respectively). CONCLUSION: Night shift duty caused both medical and
      psychological problems on the nurses. There is a need for medical surveillance,
      educational programme and the application of sleep hygiene techniques for shift
      working nurses.

PMID- 18817056
TI  - Knowledge, use and promotion of insecticide treated nets by health workers in a
      suburban town in south western Nigeria.
AB  - BACKGROUND: Morbidity and mortality associated with malaria can be significantly
      reduced by widespread use of insecticide treated nets. Health workers can
      increase acceptability of ITN by promoting its use and serving as role model.
      OBJECTIVE: To assess the knowledge, use and promotion of insecticide treated bed
      net by health workers. METHOD: This descriptive, cross sectional study was
      carried out among health care workers in Sagamu (Ogun State) between November
      2004 and January 2005. Data was collected from 263 health workers using a
      pretested, structured questionnaire. RESULT: Two hundred and forty six (93.5%)
      were aware of insecticide treated bednets (ITN) but many did not have adequate
      knowledge about it, only 52 (20.9%) knew that ITN should be retreated every 6
      months. Sixty (22.8%) were currently using ITN. In the homes where they were
      currently using ITN, children were the main users (59%). The major reasons given
      for not using an ITN were that it had not occurred to them (23.2%), 13.3% were
      satisfied with the method they were using and 12.1% felt it was not convenient to
      use. Less than one-third (32.3%) indicated that ITN was available in their health
      facility. Fifty-seven percent (56.7%) had recommended it for patients before. The
      main reasons given by those who had not recommended it before were: lack of
      knowledge about it (52.5%), while 20% indicated that they were not familiar with
      it. CONCLUSION: Awareness about ITN is high among the health workers but the
      knowledge about it is inadequate. The major challenges to use and promotion of
      ITN by health workers are lack of conviction about the unique benefits of ITN,
      inadequate knowledge and poor access to the nets.

PMID- 18817057
TI  - Salvaging twin 2 after abortion of twin 1: a case report.
AB  - We present intentional delayed delivery of twin 2 after a spontaneous membrane
      rupture and abortion oftwin1 in a dichorionic twin pregnancy at 14 weeks. As
      signs of infection were missing, we adopted a conservative (not expectant)
      management. The pregnancy was prolonged to 35 weeks' gestation. In the absence of
      additional risk factors, the role of conservative management of multiple
      pregnancies after loss of one fetus in prolonging the pregnancy to fetal
      viability in resource-poor setting is highlighted. The gained gestational age of
      20 weeks and 4 days (144 days in all), for the remaining fetus and the healthy
      mother and child pair after delivery at 35 weeks are discussed. The perinatal,
      economic and psychological implications are highlighted. The importance of good
      clinical assessment in the diagnosis of cervical incompetence and using
      ultrasound scan as a complimentary instrument is emphasized.

PMID- 18817058
TI  - Cervical plexus block for thyroidectomy: experience with a giant goitre: case
      report.
AB  - Local or regional anaesthesia has long been recognised as a useful anaesthetic
      option for thyroidectomy. A few authors have reported the successful use of local
      infiltration anaesthesia for thyroidectomy in our environment. The technique is
      said to be particularly suitable for simple giant goitres. Cervical plexus block
      has also been found useful for this operation in other parts of the world.
      However, we are unaware of any report on the use of cervical plexus block for
      thyroidectomy in our environment. We used bilateral superficial cervical plexus
      block for thyroidectomy in a 20-year old girl with a simple multinodular goitre.
      Surgery was performed with the patient in the classical thyroidectomy position.
      Though the patient was lightly sedated during the operation, the anaesthetist
      maintained communication with her throughout the procedure. Anaesthesia was
      generally effective, except for minor complaints of pressure symptoms during
      mobilization of the gland and postural aches. These, the patient described as
      tolerable. Surgery, which lasted 2 hours 45 minutes, was uneventful. The patient
      was allowed oral fluid intake within 2 hours postoperatively. Superficial
      cervical plexus block is simple, safe, effective and cheap for thyroidectomy for
      Simple Giant Goitre.

PMID- 18817059
TI  - Glaucomatocyclitic crisis in Edo State, Nigeria: report of two cases.
AB  - OBJECTIVE: To report two classical cases of glaucomatocylitic crisis in tertiary
      Health Centres in Edo State, Nigeria. METHOD: Two cases of glaucomatocylitic
      crisis seen at Irrua Specialist Teaching Hospital, Irrua, and University of Benin
      Teaching Hospital, Benin City, both in Edo State, Nigeria are reported. Diagnosis
      was based on typical history and findings on examination. RESULTS: The first was
      a female who presented in December 2002 at Irrua Specialist Teaching Hospital and
      the second was a male who presented at the University of Benin Teaching Hospital,
      in March 2004. Both presented with blurring of vision in the affected eye and
      seeing halos around light. The intraocular pressures in the affected eyes were
      markedly elevated, there were fine keratic precipitates in the corneal
      endothelium of the involved eyes and the optic discs and visual fields were
      normal. Repeated episodes of the symptoms confirmed the diagnosis
      ofglaucomatocyclitic crisis. CONCLUSION: This report shows that typical cases of
      glaucomatocylitic crisis occur in Nigerians but require a high index of suspicion
      for the diagnosis.

PMID- 18817060
TI  - High voltage electrical injuries in the University of Calabar Teaching Hospital.
AB  - BACKGROUND: Burn injuries are a common presentation in Nigerian hospitals and
      result from a variety of causes. Recently, many have resulted from Petroleum
      related fire incidents. High voltage electrical injuries are relatively rare;
      lightning strikes even rarer. In traditional societies where Traditional medicine
      practitioners are usually the first to be contacted and where late presentation
      to hospitals is the rule, complications such as the wet gangrene necessitating
      amputation are common. Even when patients present relatively early and are
      resuscitated and treated, complete prosthetic rehabilitation is difficult because
      of poverty and lack of social support systems. CASE REPORT: This review presents
      three cases of high voltage electrical burns resulting from typical 11KVA burns
      as well as lightning strike. It also highlights the role of prompt presentation
      in a health facility with appropriate resuscitation in determining good treatment
      outcomes.

PMID- 18817061
TI  - Retained products of conception in a utero cutaneous fistula: a case report.
AB  - This is a case report of a patient with utero-cutaneous fistula following
      Caesarean Section and criminal abortion. Her case was further complicated by the
      discovery of products of conception within the fistula. At laparotomy,
      adhesiolysis with the freeing of the uterus and fistulectomy were performed. She
      had an uneventful recovery.

PMID- 18817062
TI  - Antibiotic-associated pseudomembraneous colitis in a Nigerian--case report.

PMID- 18817063
TI  - Use and misuse of mobile phone in hospitals.

PMID- 18817064
TI  - Strategies to improve patients follow-up in developing countries.

PMID- 18817065
TI  - Profiling of microbial communities in a bioreactor for treating hydrocarbon
      sulfide-containing wastewater.
AB  - A technology of polymerase chain reaction-denaturing gradient gel electrophoresis
      (PCR-DGGE) was used to profile the structure and dynamic changes of microbial
      communities in a bioreactor for treating hydrocarbon-sulfide-containing (HSC)
      wastewater. The results showed that the heterotrophic genus of Acinetobacter and
      the autotrophic genera of Thiobacillus and Thiomonas could survive well in all of
      three operating conditions. Some special genera were also observed with changes
      of micro-ecoenvironment in the reactor, such as the halophilic genus of
      Nesterenkonia. Further, a new genus was found in the reactor, which was likely to
      have the ability to degrade sulfide and hydrocarbon at the same time. All of
      these detected and the new found genera have widely applicable potential in the
      treatment of HSC wastewater.

PMID- 18817066
TI  - Effects of Cd2+ and Pb2+ on the substrate biofilms in the integrated vertical
      flow constructed wetland.
AB  - The effects of single Cd2+ and Pb2+, and combined Cd2+ and Pb2+ on dehydrogenase
      activity and polysaccharide content of the substrate biofilms in the integrated
      vertical-flow constructed wetland (IVCW) were studied. Dehydrogenase activities
      decreased linearly with the increasing concentrations of Cd2+ and Pb2+ at
      different times (6, 24, 72, and 120 h). The activities at both 6 and 24 h were
      significantly higher than that at 72 and 120 h in the case of single and combined
      treatments. The single Cd2+ and Pb2+ treatments significantly inhibited
      dehydrogenase activities at concentrations in excess of 20 micromol/L Cd2+ and 80
      micromol/L Pb2+, respectively. The inhibitory effect of Cd2+ was much greater
      than that of Pb2+. At the same time, the combined treatment of Cd2+ and Pb2+
      significantly inhibited dehydrogenase activities at all five concentrations
      studied and the lowest combined concentration was 1.25 micromol/L Cd2+ and 5
      micromol/L Pb2+. A synergistic effect of Cd2+ and Pb2+ was observed. On the other
      hand, polysaccharide contents varied unpredictably with the increasing
      concentrations of Cd2+ and Pb2+ and extended experimental time. There were no
      significant statistical differences within the range of concentration and time
      studied, whether singly or in combination. These results implied that the effects
      of heavy metals on biofilms should be a concern for the operation and maintenance
      of constructed wetlands.

PMID- 18817067
TI  - Effects of low temperature on aluminum(III) hydrolysis: theoretical and
      experimental studies.
AB  - In this study, the effects of low temperature on aluminum(III) (Al) hydrolysis
      were examined both theoretically and experimentally by constructing a solubility
      diagram for amorphous aluminum hydroxide (Al(OH)3(am)) and a distribution diagram
      of hydrolyzed Al species. First, thermodynamic data of Al species at 4 degrees C
      were calculated from that at 25 degrees C. A well confirmed polymeric Al species,
      AlO4Al12(OH)24(7+)(Al13), was involved in building the diagrams and,
      correspondingly, the non-linear simultaneous equations with 13 degrees were
      resolved. Secondly, polarized Zeeman atomic absorption spectrophotometry (AAS),
      27Al nuclear magnetic resonance (NMR) spectroscopy, and ferron-based
      spectrophotometry were applied for constructing the practical diagrams. The
      results show that a decrease of temperature from 25 to 4 degrees C caused the
      Al(OH)3(am) boundary on the solubility diagram to shift toward the alkaline side
      by about 1.0 pH unit and the minimum solubility of Al(OH)3(am) to reduce by 1.0
      log unit. The distribution diagram indicates that the monomeric Al, Al13, and
      solid-phase Al(OH)3 were alternately the predominant species with the increase of
      pH value during Al hydrolysis. At 25 degrees C, Al13 was the dominant species in
      a pH range of 4.0 to 4.5, whereas at 4 degrees C, All3 was the leading species in
      a pH range spaced from 4.5 to 6.3. The predominant species changed from the
      monomeric Al to the solid-phase Al(OH)3 over the range of 1.8 pH units at 4
      degrees C in comparison with the range of 0.5 pH unit at 25 degrees C.

PMID- 18817068
TI  - Reduction of nitrobenzene by the catalyzed Fe/Cu process.
AB  - The polarization behavior of the couple Fe/Cu in 100 mg/L nitrobenzene aqueous
      solution was studied using Evans coupling diagrams. The results indicated that
      the iron corrosion was limited by both anodic and cathodic half-cell reactions
      under the neutral conditions, and cathodically controlled under the alkaline
      conditions. Batch experiments were performed to study the effect of solution pH,
      reaction duration, concentration, type of electrolyte, and dissolved oxygen (DO)
      on the reduction of nitrobenzene by the catalyzed Fe/Cu process. This process
      proved effective in the pH range of 3 to 11. The conversion efficiency of
      nitrobenzene at pH around 10.1 was almost the same as that under highly acid
      conditions (pH around 3). The degradation of nitrobenzene fell into two phases:
      adsorption and surface reduction, and the influence of adsorption and mass
      transfer became more extensive with solution concentration. The reduction rate
      decreased in the presence of DO in the solution, indicating that a need for
      aeration was eliminated in the catalyzed Fe/Cu process. Accordingly, spending on
      energy consumption would be reduced. Economic analysis indicated that merely 0.05
      kg was required for the treatment of a ton of nitrobenzene-containing water with
      pH from 3 to 11. The catalyzed Fe/Cu process is cost-effective and of practical
      value.

PMID- 18817069
TI  - Activated sludge-mediated biodegradation of dimethyl phthalate under fermentative
      conditions.
AB  - The biodegradation of dimethyl phthalate (DMP) was investigated under
      fermentative conditions in this study. The nature of the intermediate compounds
      and the extent of mineralization were probed using high-pressure liquid
      chromatography (HPLC) and liquid chromatography-mass spectrometry (LC-MS)
      methods. The fermentative bacteria were able to biodegrade the DMP under
      anaerobic conditions, with the biodegradation rate of 0.36 mg DMP/(L x h). The
      results demonstrated that the DMP degradation under fermentative conditions
      followed the modified Gompertz model with the correlation coefficient of 0.99.
      Monomethyl phthalate (MMP) and phthalic acid (PA) were detected as the
      intermediates of DMP biodegradation. During the experiment, MMP was rapidly
      produced and removed; however, PA accumulated as the biodegradation was slower
      throughout the course of the experiment. The COD(Cr) concentration decreased from
      245.06 to 72.01 mg/L after the experimental operation of 20 d. The volume of
      methane produced was 3.65 ml over a period of 20 d and the amount of methane
      recovered corresponded to 40.2% of the stoichiometric value. The COD(Cr)
      variation and methane production showed that the DMP could not be completely
      mineralized under the fermentative conditions, which implied that the
      fermentative bacteria were not able to biodegrade DMP entirely.

PMID- 18817070
TI  - De-colorization of Reactive Brilliant Orange X-GN by a novel rotating
      electrochemical disc process.
AB  - A novel electrochemical setup for wastewater treatment-rotating electrochemical
      disc process (RECDP) was developed in this article. The anode and cathode are
      distributed alternatively and evenly on a flat round disc, which was designed to
      improve mass transfer of organics from bulk solution to electrode surface, while
      at the same time increasing oxygen transfer from air to the liquid to benefit the
      organics oxidization. The color removal of dye Reactive Brilliant Orange X-GN
      (RBO) was experimentally investigated using the setup. The results show that the
      RECDP could efficiently remove the color by 99.5% after 60-min electrolysis. The
      influence of factors such as the disc rotating speed, current intensity, pH, and
      treating time was also explored, and the de-colorization mechanism was studied
      with electron paramagnetic resonance (EPR), UV-Vis, and IR. It has been confirmed
      that the free radicals oxidization leads to the dye de-coloration.

PMID- 18817071
TI  - Effects of COD/N ratio and DO concentration on simultaneous nitrification and
      denitrification in an airlift internal circulation membrane bioreactor.
AB  - The effects of chemical oxygen demand and nitrogen (COD/N) ratio and dissolved
      oxygen concentration (DO) on simultaneous nitrification and denitrification (SND)
      were investigated using an airlift internal circulation membrane bioreactor (AIC
      MBR) with synthetic wastewater. The results showed that the COD efficiencies were
      consistently greater than 90% regardless of changes in the COD/N ratio. At the
      COD/N ratio of 4.77 and 10.04, the system nitrogen removal efficiency became
      higher than 70%. However, the nitrogen removal efficiency decreased to less than
      50%, as the COD/N ratio shifted to 15.11. When the operating DO concentration was
      maintained at 1.0 mg/L in AIC-MBR, a satisfying SND was achieved. Either low or
      high DO concentration could restrain SND.

PMID- 18817072
TI  - Effect of inorganic carbon on anaerobic ammonium oxidation enriched in sequencing
      batch reactor.
AB  - The present lab-scale research reveals the enrichment of anaerobic ammonium
      oxidation microorganism from methanogenic anaerobic granular sludge and the
      effect of inorganic carbon (sodium bicarbonate) on anaerobic ammonium oxidation.
      The enrichment of anammox bacteria was carried out in a 7.0-L sequencing batch
      reactor (SBR) and the effect of bicarbonate on anammox was conducted in a 3.0-L
      SBR. Research results, especially the biomass, showed first signs of anammox
      activity after 54 d cultivation with synthetic wastewater, when the pH was
      controlled between 7.5 and 8.3, the temperature was 35 degrees C. The anammox
      activity increased as the influent bicarbonate concentration increased from 1.0
      to 1.5 g/L, and then, was inhibited as the bicarbonate concentration approached
      2.0 g/L. However, the activity could be restored by the reduction of bicarbonate
      concentration to 1.0 g/L, as shown by rapid conversion of ammonium, and nitrite
      and nitrate production with normal stoichiometry. The optimization of the
      bicarbonate concentration in the reactor could increase the anammox rate up to
      66.4 mgN/(L x d).

PMID- 18817073
TI  - Dechlorination of disinfection by-product monochloroacetic acid in drinking water
      by nanoscale palladized iron bimetallic particle.
AB  - Nanoscale palladized iron (Pd/Fe) bimetallic particles were prepared by reductive
      deposition method. The particles were characterized by X-ray diffraction (XRD), X
      ray fluorescence (XRF), scanning electron microscope (SEM), transmission electron
      microscope (TEM), and Brunauer-Emmett-Teller-nitrogen (BET-N2) method. Data
      obtained from those methods indicated that nanoscale Pd/Fe bimetallic particles
      contained alpha-Fe0. Detected Pd to Fe ratio by weight (Pd/Fe ratio) was close to
      theoretical value. Spherical granules with diameter of 47 +/- 11.5 nm connected
      with one another to form chains and the chains composed nanoscale Pd/Fe
      bimetallic particles. Specific surface area of particles was 51 m2/g. The
      factors, such as species of reductants, Pd/Fe ratio, dose of nanoscale Pd/Fe
      bimetallic particles added into solutions, solution initial pH, and a variety of
      solvents were studied. Dechlorination effect of monochloroacetic acid by
      different reductants followed the trend: nanoscale Pd/Fe bimetallic particles of
      0.182% Pd/Fe > nanoscale Fe > reductive Fe. When the Pd/Fe ratio was lower than
      0.083%, increasing Pd/Fe ratio would increase dechlorination efficiency (DE) of
      MCAA. When the Pd/Fe ratio was higher than 0.083%, increasing Pd/Fe ratio caused
      a decrease in DE. Adding more nanoscale Pd/Fe bimetallic particles to solution
      would enhance DE. The DE of MCAA decreased as initial pH of solution increased.

PMID- 18817074
TI  - Combination of adsorption and biodegradation processes for textile effluent
      treatment using a granular activated carbon-biofilm configured packed column
      system.
AB  - The objective of this study was to investigate the feasibility of using a
      granular activated carbon-biofilm configured packed column system in the
      decolorization of azo dye Acid Orange 7-containing wastewater. The Acid Orange 7
      degrading microbial from anaerobic sequencing batch reactor which treating the
      azo dye-containing wastewater for more than 200 d was immobilized on spent
      granular activated carbon (GAC) through attachment. The GAC-biofilm configured
      packed column system showed the ability to decolorize 100% of the azo dye when
      working at high loading rate of Acid Orange 7 at 2.1 g/(L x d) with treatment
      time of 24 h. It was observed that the decolorization rate increased along with
      the increasing of initial Acid Orange 7 concentrations, until it reached an
      optimum point at about 0.38 g/h with initial Acid Orange 7 concentrations of
      1,150 mg/L and the decolorization rate tend to be declined beyond this
      concentration.

PMID- 18817075
TI  - Intercross real-time control strategy in alternating activated sludge process for
      short-cut biological nitrogen removal treating domestic wastewater.
AB  - To develop technically feasible and economically favorable dynamic process
      control (DPC) strategies for an alternating activated sludge (AAS) system, a
      bench-scale continuous-flow alternating aerobic and anoxic reactor, performing
      short-cut nitrogen removal from real domestic wastewater was operated under
      different control strategies for more than five months. A fixed-time control
      (FTC) study showed that bending-points on pH and oxidation-reduction potential
      (ORP) profiles accurately coincided with the major biological activities.
      "Ammonia valley" on the pH profile represented the end of nitrification, whereas,
      the "nitrite knee" on the ORP profile and "nitrite apex" on the pH profile both
      indicated the end of denitrification. Therefore, a new reliable and effective
      real-time control strategy was developed using pH and ORP as control parameters,
      to improve the performance of the AAS process. The online control strategy could
      achieve up to 87% of the total nitrogen (TN) removal efficiency on an average,
      and saving approximately 20% aeration energy, as compared to the conventional
      steady-state control systems. Moreover, stable short-cut nitrification and
      denitrification were successfully achieved with an average nitrite accumulation
      ratio of above 95%.

PMID- 18817076
TI  - Treatment of tunnel wash waters--experiments with organic sorbent materials. Part
      I: Removal of polycyclic aromatic hydrocarbons and nonpolar oil.
AB  - Tunnel wash waters characterize all waters that run off after washing procedures
      of tunnels are performed. These waters represent a wide spectrum of organic and
      inorganic pollutants, such as polycyclic aromatic hydrocarbons (PAHs) and toxic
      metals. Removal of such contaminants from water runoff was investigated using
      laboratory tests after washing procedure was performed on two road tunnels in
      eastern Norway (Hanekleiv and Bragernes). Due to diverse character of both,
      treatment media and treated wash waters, the whole investigation was divided into
      two separate laboratory experiments. The treatment efficiencies were established
      based on the levels of concentrations and reductions of the measured contaminants
      in the effluents released from the tested media. In the first part of the
      article, the contents of nonpolar oil (NPO), 16 individual PAHs, and total PAHs
      are described. This part revealed that the combination of two organic sorbent
      materials provided the highest treatment efficiency for wash waters released from
      the road tunnel and from electrostatic filters. The greatest reduction levels
      reached 97.6% for NPO, 97.2% for benzo[a]pyrene, and 96.5% for the total PAHs. In
      the second part of the article, the concentrations and the removal rates of toxic
      metals are reported.

PMID- 18817077
TI  - Extraction of copper from sewage sludge using biodegradable chelant EDDS.
AB  - [S,S]-Ethylenediaminedisuccinic acid (EDDS), a biodegradable chelant, was used to
      separate the heavy metals from the sewage sludge based on chemical extraction
      technology. Under various conditions, the extraction experiments were carried out
      for the sewage sludge from Shanghai Taopu Municipal Wastewater Plant, China. The
      influences of pH and the concentration of EDDS on the extraction efficiency for
      copper (Cu) were discussed. The results showed that EDDS had higher extraction
      efficiency for Cu from the sewage sludge than other heavy metals. The system pH
      and the concentration of EDDS had a significant effect on the extraction
      efficiency. The extraction efficiency of Cu increased gradually with the increase
      of system pH and reached a higher efficiency within pH range of 3-10. The
      extraction efficiency maintained at approximately 70% when the pH > or = 4.5 and
      the molar ratio of EDDS to total heavy metals was 10:1. From the fractional
      analysis of the heavy metals in sewage sludge before and after the extraction, it
      was found that the extracted Cu mainly came from the following four fractions,
      i.e. water soluble, acid-soluble, reducible, and oxidizable fractions.

PMID- 18817078
TI  - Stimulatory effects of biosurfactant produced by Pseudomonas aeruginosa BSZ-07 on
      rice straw decomposing.
AB  - Biosurfactant, produced by Pseudomonas aeruginosa BSZ-07, was added to the rice
      straw decomposing process to enhance the production of reducing sugars. Observed
      by Fourier Transform InfraRed (FT-IR) and Nuclear Magnetic Resonance (NMR)
      analysis, the purified biosurfactant was considered as a mixture of RL1 and RL2,
      which are two different types of rhamnolipids. Two different adding methods,
      adding the purified rhamnolipid and the on-site production of it were compared.
      The results showed that 0.5 g/L was the optimum concentration for adding purified
      rhamnolipid and the optimum temperature for on-site production was 30 degrees C
      for the first 48 h and 34 degrees C for the next 48 h. Under the optimum
      conditions, these two adding methods could improve the production of reducing
      sugar to 2.730 and 2.504 g/L, which was 22.30% and 12.20% higher than that of the
      rhamnolipid-free sample, respectively, which indicated that both of them were
      more effective than any other kind of surfactant discussed in this article. As
      the on-site production of rhamnolipid could omit the purification process, thus
      reducing the production cost effectively, it seemed to be a prospective adding
      method of the biosurfactant for enhancing rice straw decomposing.

PMID- 18817079
TI  - Microbial community diversity in the profile of an agricultural soil in northern
      China.
AB  - The soil microorganisms at different depths play an important role in soil
      formation, ecosystem biogeochemistry, recycling of nutrients, and degradation of
      waste products. The aims of this study were to observe the microbial diversity in
      the profile of an agricultural soil in northern China, and to research the
      correlation between soil microbes and geochemistry. First, the soil geochemistry
      of the profile was investigated through 25 chemical elements. Secondly, the
      various physiological groups of microorganisms were studied by traditional
      culture methods. Thirdly, the functional diversity on sole carbon source
      utilization (SCSU) was evaluated by the BIOLOG system. Finally, the correlation
      between the soil microbial diversity and geochemistry was analyzed statistically.
      The results showed that the amounts and proportions of various physiological
      groups of microorganisms changed with depth. The bacterial functional diversity
      on SCSU decreased with increasing depth, but evenness of the substrate
      utilization increased. Although the microbial metabolic diversity was different
      at every depth, it could be classified into three main groups by principal
      component analysis and cluster analysis. The various physiological groups of
      microorganisms showed remarkable correlation with relevant soil chemical
      elements. The sensitive microbial indicators of soil health were expected to be
      screened out from actinomyces or ammonifying bacteria.

PMID- 18817080
TI  - A risk assessment system for alien plant bio-invasion in Xiamen, China.
AB  - Bio-invasion has caused serious ecosystem damage and enormous economic losses in
      China, and it has been the greatest factor to island bio-diversity reduction.
      Xiamen, as an important seaport with a relatively high conservation value, is
      particularly vulnerable to bio-invasion for its typical island ecosystem as well
      as frequent human-made disturbance. As a result of field surveys, literature
      review, and consultation with experts, a list of 67 alien plants identified as
      major invaders (12 species) and emerging invaders (55 species) in Xiamen has been
      compiled. Based on the analysis of the current situation of bio-invasion in
      Xiamen, a risk assessment system for alien plant invasion has been designed using
      a ranking system and an analytic hierarchy process. The system consists of 17
      secondary indices, grouped into 6 primary indices reflecting the different stages
      in the bio-invasion process: introduction, establishment, dispersion, current
      range, infestation, and artificial control. Biogeographical, ecological, and
      experience-linked aspects of the species as well as artificial disturbance were
      taken into account in the index selection and criterion development. The system
      was then validated (and worked well) using fifty well-known alien plant species
      as candidates. Appropriate recommendations are proposed to help local policy
      makers prioritize their decisions on such alien plants.

PMID- 18817081
TI  - Environmental monitoring and fuzzy synthetic evaluation of municipal solid waste
      transfer stations in Beijing in 2001-2006.
AB  - Transfer station (TS) is an integral part of present-day municipal solid waste
      (MSW) management systems. To provide information for the incorporation of waste
      facilities within the current integrated waste management system, the authors
      measured the existing environmental quality at five MSW TSs. Discharged
      wastewater, air, and noise were monitored and assayed at the five TSs in Beijing
      in 2001-2006 during rainy seasons (RSs) and dry seasons (DSs). Except Ammonia
      (NH3) and hydrogen sulfide (H2S), the analytical results of total suspended
      particles (TSPs), odor, noise, ammonium nitrogen (NH4(+)-N), chemical oxygen
      demand (COD(Cr)), biochemical oxygen demand (BOD5), suspended solid (SS), and
      fecal coliform concentrations were all degree-varied higher than the criteria
      limit in China. Using fuzzy mathematics, the environmental quality of MSW TSs in
      Beijing was classified into five categories, with levels of certainty of
      belonging to different categories and evaluations. The result indicated that the
      whole environmental quality of Datun TS, Majialou TS, and Xiaowuji TS, in
      Beijing, were bad during 2001-2006 in RSs and DSs. Except in 2002, the entire
      environmental quality of the Wuluju TS during 2001-2006 in RSs was poor. Only in
      the DSs of 2002 and 2003 was the whole environmental quality of the Wuluju TS
      good. The whole environmental quality of the Yamenkou TS during 2001-2006 in DSs
      was bad, which was lower than that of 2001-2006 DSs.

PMID- 18817082
TI  - Study on superoxide and hydroxyl radicals generated in indirect electrochemical
      oxidation by chemiluminescence and UV-Visible spectra.
AB  - The generation and transformation of radicals on the cathode of indirect
      electrochemical oxidation were studied by chemiluminescence (CL) and UV-Visible
      spectra in the reactor with a salt bridge that connected the separated chambers.
      The CL intensity of 4 x 10(-9) mol/L luminol on the cathode with bubbling oxygen
      was about seven times that of the intensity without it, which was because of the
      generation of reactive oxygen species (ROS). The existence of ROS, especially the
      generation of the superoxide radical, could be affirmed by the fact that the CL
      intensity of 4 x 10(-9) mol/L 2-methyl-6-(4-methoxyphenyl)-3,7-dihydroimidazo[1,2
      a]pyrazin-3-one with bubbling oxygen was about four times that of the intensity
      without it. However, there was no chemiluminescence on the anode under the same
      condition. The change in the UV-Visible spectra of nitro blue tetrazolium and N,N
      dimethyl-4-nitrosoaniline at the cathode chamber affirmed the transformation from
      oxygen to superoxide and hydroxyl radicals. The mechanism of the superoxide and
      hydroxyl radical generation and transformation on the cathode was discussed with
      the help of the experimental results and relative references.

PMID- 18817083
TI  - Naphthalene emissions from moth repellents or toilet deodorant blocks determined
      using head-space and small-chamber tests.
AB  - The present study investigated the emissions of naphthalene and other compounds
      from several different moth repellents (MRs) and one toilet deodorant block (TDB)
      currently sold in Korea, using a headspace analysis. The emission factors and
      emission rates of naphthalene were studied using a small-scale environmental
      chamber. Paper-type products emitted a higher concentration of the total volatile
      organic compounds (VOCs) (normalized to the weight of test piece) than ball-type
      products, which in turn emitted higher concentration than a gel-type product. In
      contrast, naphthalene was either the most or the second highest abundant compound
      for the four ball products, whereas for paper and gel products it was not
      detected or was detected at much lower levels. The abundance of naphthalene
      ranged between 18.4% and 37.3% for ball products. The results showed that the
      lower the air changes per hour (ACH) level was, the higher the naphthalene
      concentrations became. In general, a low ACH level suggests a low ventilation
      rate. The emission factor for naphthalene was nearly 100 times higher for a ball
      MR than for a gel or a paper MR. For the ball MR, the lower ACH level resulted in
      higher emission rate.

PMID- 18817084
TI  - Urea hydrolysis and recovery of nitrogen and phosphorous as MAP from stale human
      urine.
AB  - Laboratory-scale tests for magnesium ammonium phosphate (MAP) precipitation
      following urea hydrolysis of human urine were conducted using orthogonal
      experiment design. The effects of initial pH, temperature and the volumetric
      ratios of stale urine to fresh urine, on urea hydrolysis in urine were studied to
      determine the final hydrolysis time to recover most nitrogen from separated human
      urine by MAP. With a volumetric ratio of stale to fresh urine > 10% and at
      temperature > or = 20 degrees C, urea hydrolysis could be completed in two days.
      Alkaline pH inhibited urea hydrolysis progress. The final pH values were all
      around 9.0 following urine hydrolysis, while the suspension pH might act as an
      indicator to detect the start and extent of urea hydrolysis. Over 95% of ammonium
      nitrogen and over 85% of phosphorus from hydrolyzed urine as MAP precipitate were
      obtained using MgCl2.6H2O and Na2HPO4 x 12H2O as precipitation agents at pH 8.5,
      molar ratio of Mg2+:NH4(+)-N:PO4(3-)-P at (1.2-1.3):1:1, mixing speed of 120
      r/min, and precipitation time and reaction time of 3 h and 15 min, respectively.
      The precipitate has a structure resembling pure MAP crystal.

PMID- 18817085
TI  - Metastases of clinically occult testicular seminoma mimicking primary
      extragonadal retroperitoneal germ cell tumors.
AB  - BACKGROUND: Whether extragonadal germ cell tumors develop primarily in the
      retroperitoneum or whether they are essentially metastases of a primary
      testicular tumor has long been debated and remains controversial. PATIENTS AND
      METHODS: Three patients presenting with apparent primary extragonadal
      retroperitoneal germ cell tumors are reported. Ipsilateral testicular evaluation
      was extended with palpation, ultrasonography and finally histological
      examination. RESULTS: The retroperitoneal extragonadal tumors were found during
      abdominal MSCT. It was a fortuitous finding in the two first patients.The third
      patient presented with abdominal pain attributed to necrosis of the large mass
      which was subsequently firstly drained through endoscopic ultrasound-guided
      transduodenal puncture. The seminomatous nature of the retroperitoneal tumors was
      obtained through transduodenal echoendoscopic-guided cytopuncture in the first
      case, celioscopic resection in the second case and delayed percutaneous CT guided
      biopsy in the third symptomatic case. The first two patients had a history of
      cryptorchidism with substantial clinical testicular atrophy; ultrasonography
      showed microlithiasis and a small intratesticular tumor in the first patient and
      an hypoechoic but rather homogeneous atrophic testis in the other; orchiectomy
      confirmed small seminomatous intratesticular tumors in the two cases. The third
      patient had an atypical hypoechoic area on testicular ultrasound and
      histopatholgy revealed a burn-out primary tumor. CONCLUSIONS: So-called primary
      extragonadal retroperitoneal germ cell tumors are extremely rare and should first
      be considered as metastases of a viable or burned-out testicular cancer until
      proven otherwise. All ipsilateral testicular abnormalities revealed by the
      patient's history, clinical examination and mostly by testicular ultrasound must
      be treated adequately with orchiectomy because they may act as a sanctuary for
      later tumor growth.

PMID- 18817086
TI  - The use of duplex doppler ultrasound in a case of multifocal hepatic hemangioma.
AB  - A one-month-old girl presented with multiple cutaneous hemangiomas, abnormal
      weight gain, hepatomegaly, and symptoms of bleeding disorder. Abdominal
      ultrasound and CT revealed a multifocal hypervascular hepatic tumor and signs of
      vascular overload. Biopsy confirmed the presence of an infantile hepatic
      hemangioma. Conservative treatment with high dose steroids showed regression of
      the hepatic lesions and the signs of vascular congestion. Ultrasound was used for
      follow-up and its role in treatment monitoring is discussed in this manuscript.

PMID- 18817087
TI  - Ileal inflammatory fibroid polyp causing ileocolic intussusception.
AB  - Inflammatory Fibroid Polyp (IFP) is an extremely rare tumour involving the
      gastrointestinal tract (GI) and especially the stomach and small bowel. It
      presents either as a solitary large or sessile lesion arising from the submucosa
      and despite a large size and sometimes infiltrating growth, the tumour is always
      benign and has a good prognosis. Histogenesis remains unknown and controversial.
      We report an ileal case presenting classically and typically with ileocolic
      intussusception. Diagnosis was made preoperatively with abdominal mdCT. The polyp
      itself does not have noteworthy radiological signs but must be included in the
      large essentially histological differential diagnosis of GI tumours.

PMID- 18817088
TI  - Isolated noncompaction of ventricular myocardium. Diagnosis with multidetector
      computed tomography.
AB  - Noncompaction of the ventricular myocardium is a cardiomyopathy thought to be
      caused by arrest of normal embryogenesis of the endocardium and myocardium. Non
      compaction presents as an isolated form or in association with other congenital
      anomalies, such as obstruction of the right or left ventricular outflow tracts,
      complex cyanotic congenital heart disease and coronary artery anomalies. Contrast
      enhanced CT is capable of showing the abnormal architecture of the left
      ventricular wall in non-compaction but is also able to evaluate the coronary
      arteries to exclude anomalies or significant stenosis, which is usually not
      possible with MRI or echocardiography.

PMID- 18817089
TI  - Multivesicular mediastinal hydatid cyst presenting with left recurrent and
      phrenic nerve palsy.
AB  - Hydatid disease caused by Echinococcus granulosus is endemic in Indian
      subcontinent and a common surgical problem. Although hydatid cyst is common in
      the liver and lung, it can be encountered in almost every part of the body.
      Mediastinal hydatid disease is a rare occurrence and only a few cases have been
      reported in the literature.The present article reports a case of a multivesicular
      mediastinal hydatid cyst associated with nerve palsies.The patient presented with
      left recurrent nerve and phrenic nerve palsy. Ultrasonography (US) and computed
      tomography (CT) of the thorax revealed a multivesicular cyst in the superior
      mediastinum, the cyst fluid was aspirated and sent for cytology which confirmed
      the echinococcus as the cause of cystic lesion. Surgical exploration was done by
      left anterolateral thoracotomy and the cyst was excised. The aim of the present
      article is to make the reader aware of such rare presentation of hydatid disease
      especially in endemic areas.

PMID- 18817090
TI  - Acute calcific prevertebral tendinitis.
AB  - Acute calcific prevertebral tendinitis, also known as retropharyngeal calcific
      tendinitis and longus colli tendinitis, is an uncommon benign condition
      presenting as acute neck pain.Typical characteristics of this entity are
      calcifications at the superior insertion of the longus colli tendons at C1-C2
      level and a fluid collection in the retropharyngeal space. Differential diagnosis
      consists of retropharyngeal abscess, traumatic injury or infectious spondylitis.
      Knowledge of the clinical and imaging findings can prevent misdiagnosis with
      inappropriate attempts at surgical drainage.

PMID- 18817091
TI  - Exotic pathology of the hand and foot. A pictorial review.
AB  - In this article, the imaging findings of the most frequently encountered import
      pathology of the hand and foot are reviewed, including leprosy, loiasis, snake
      bites or penetration of spines of sea urchins in the hand and foot. Our objective
      is to familiarize the radiologist of the Western countries with these diseases,
      which are still prevalent in developing areas. Due to the rising traveling to
      foreign countries and continuous immigration, it is important that these
      disorders be considered in the differential diagnosis in a specific population of
      asylum-seekers, economic refugees and any other group of persons traveling around
      the globe. Imaging findings on conventional radiography will be emphasized.

PMID- 18817092
TI  - Current management of lobular in situ neoplasia.
AB  - Although the term of lobular neoplasia was first proposed in 1978 and the term
      Lobular In situ Neoplasia (LIN) has been incorporated in the current World Health
      Organisation (WHO) classification to cover both atypical lobular hyperplasia
      (ALH) and lobular carcinoma in situ (LCIS), the clinical significance and the
      natural history of lobular neoplasia is far from being fully understood.
      Furthermore problems and confusion still remain surrounding (1) the most
      appropriate terminology and classification for these lesions, (2) the best course
      of long-term management after diagnosis.This article summarizes the opinions on
      LCIS management of a group of Belgian experts.

PMID- 18817093
TI  - INTERLUDE: A duck in a dog.

PMID- 18817094
TI  - INTERLUDE: pseudo-metastases on whole body bone scan.

PMID- 18817095
TI  - A stroke-like episode in a young patient with MELAS syndrome.

PMID- 18817096
TI  - Giant sigmoid diverticulum: not an innocent finding.

PMID- 18817097
TI  - Sternal insufficiency fracture.

PMID- 18817098
TI  - The Mount Fuji sign in tension pneumocephalus.

PMID- 18817099
TI  - Popcorn calcifications in osteogenesis imperfecta.

PMID- 18817100
TI  - Large mammographic opacity due to hamartoma.

PMID- 18817101
TI  - Massive inguinoscrotal hernia of the bladder.

PMID- 18817102
TI  - Nasopalatine duct cyst.

PMID- 18817103
TI  - Textiloma on PET-CT.

PMID- 18817104
TI  - A special issue of JA&WMA on agricultural air quality: state of the science.

PMID- 18817105
TI  - Air emissions of ammonia and methane from livestock operations: valuation and
      policy options.
AB  - The animal husbandry industry is a major emitter of ammonia (NH3), which is a
      precursor of fine particulate matter (PM2.5)--arguably, the number-one
      environment-related public health threat facing the nation. The industry is also
      a major emitter of methane (CH4), which is an important greenhouse gas (GHG). We
      present an integrated process model of the engineering economics of technologies
      to reduce NH3 and CH4 emissions at dairy operations in California. Three policy
      options are explored: PM offset credits for NH3 control, GHG offset credits for
      CH4 control, and expanded net metering policies to provide revenue for the sale
      of electricity generated from captured methane (CH4) gas. Individually these
      policies vary substantially in the economic incentives they provide for farm
      operators to reduce emissions. We report on initial steps to fully develop the
      integrated process model that will provide guidance for policy-makers.

PMID- 18817106
TI  - Characterizing ammonia emissions from swine farms in eastern North Carolina: part
      1--conventional lagoon and spray technology for waste treatment.
AB  - Ammonia (NH3) fluxes from waste treatment lagoons and barns at two conventional
      swine farms in eastern North Carolina were measured. The waste treatment lagoon
      data were analyzed to elucidate the temporal (seasonal and diurnal) variability
      and to derive regression relationships between NH3 flux and lagoon temperature,
      pH and ammonium content of the lagoon, and the most relevant meteorological
      parameters. NH3 fluxes were measured at various sampling locations on the lagoons
      by a flowthrough dynamic chamber system interfaced to an environmentally
      controlled mobile laboratory. Two sets of open-path Fourier transform infrared
      (FTIR) spectrometers were also used to measure NH3 concentrations for estimating
      NH3 emissions from the animal housing units (barns) at the lagoon and spray
      technology (LST) sites. Two different types of ventilation systems were used at
      the two farms. Moore farm used fan ventilation, and Stokes farm used natural
      ventilation. The early fall and winter season intensive measurement campaigns
      were conducted during September 9 to October 11, 2002 (lagoon temperature ranged
      from 21.2 to 33.6 degrees C) and January 6 to February 2, 2003 (lagoon
      temperature ranged from 1.7 to 12 degrees C), respectively. Significant
      differences in seasonal NH3 fluxes from the waste treatment lagoons were found at
      both farms. Typical diurnal variation of NH3 flux with its maximum value in the
      afternoon was observed during both experimental periods. Exponentially increasing
      flux with increasing surface lagoon temperature was observed, and a linear
      regression relationship between logarithm of NH3 flux and lagoon surface
      temperature (T1) was obtained. Correlations between lagoon NH3 flux and chemical
      parameters, such as pH, total Kjeldahl nitrogen (TKN), and total ammoniacal
      nitrogen (TAN) were found to be statistically insignificant or weak. In addition
      to lagoon surface temperature, the difference (D) between air temperature and the
      lagoon surface temperature was also found to influence the NH3 flux, especially
      when D > 0 (i.e., air hotter than lagoon). This hot-air effect is included in the
      statistical-observational model obtained in this study, which was used further in
      the companion study (Part II), to compare the emissions from potential
      environmental superior technologies to evaluate the effectiveness of each
      technology.

PMID- 18817107
TI  - Characterizing ammonia emissions from swine farms in eastern North Carolina: part
      2--potential environmentally superior technologies for waste treatment.
AB  - The need for developing environmentally superior and sustainable solutions for
      managing the animal waste at commercial swine farms in eastern North Carolina has
      been recognized in recent years. Program OPEN (Odor, Pathogens, and Emissions of
      Nitrogen), funded by the North Carolina State University Animal and Poultry Waste
      Management Center (APWMC), was initiated and charged with the evaluation of
      potential environmentally superior technologies (ESTs) that have been developed
      and implemented at selected swine farms or facilities. The OPEN program has
      demonstrated the effectiveness of a new paradigm for policy-relevant
      environmental research related to North Carolina's animal waste management
      programs. This new paradigm is based on a commitment to improve scientific
      understanding associated with a wide array of environmental issues (i.e., issues
      related to the movement of N from animal waste into air, water, and soil media;
      the transmission of odor and odorants; disease-transmitting vectors; and airborne
      pathogens). The primary focus of this paper is on emissions of ammonia (NH3) from
      some potential ESTs that were being evaluated at full-scale swine facilities.
      During 2-week-long periods in two different seasons (warm and cold), NH3 fluxes
      from water-holding structures and NH3 emissions from animal houses or barns were
      measured at six potential EST sites: (1) Barham farm--in-ground ambient
      temperature anaerobic digester/energy recovery/greenhouse vegetable production
      system; (2) BOC #93 farm--upflow biofiltration system--EKOKAN; (3) Carrolls farm-
      aerobic blanket system--ISSUES-ABS; (4) Corbett #1 farm--solids separation/
      gasification for energy and ash recovery centralized system--BEST; (5) Corbett #2
      farm--solid separation/ reciprocating water technology--ReCip; and (6) Vestal
      farm--Recycling of Nutrient, Energy and Water System--ISSUES-RENEW. The ESTs were
      compared with similar measurements made at two conventional lagoon and spray
      technology (LST) farms (Moore farm and Stokes farm). A flow-through dynamic
      chamber system and two sets of open-path Fourier transform infrared (OP-FTIR)
      spectrometers measured NH3 fluxes continuously from water-holding structures and
      emissions from housing units at the EST and conventional LST sites. A statistical
      observational model for lagoon NH3 flux was developed using a multiple linear
      regression analysis of 15-min averaged NH3 flux data against the relevant
      environmental parameters measured at the two conventional farms during two
      different seasons of the year. This was used to compare the water-holding
      structures at ESTs with those from lagoons at conventional sites under similar
      environmental conditions. Percentage reductions in NH3 emissions from different
      components of each potential EST, as well as the whole farm on which the EST was
      located were evaluated from the estimated emissions from water-holding
      structures, barns, etc., all normalized by the appropriate nitrogen excretion
      rate at the potential EST farm, as well as from the appropriate conventional
      farm. This study showed that ammonia emissions were reduced by all but one
      potential EST for both experimental periods. However, on the basis of our
      evaluation results and analysis and available information in the scientific
      literature, the evaluated alternative technologies may require additional
      technical modifications to be qualified as unconditional ESTs relative to NH3
      emissions reductions.

PMID- 18817108
TI  - Footprints on ammonia concentrations from environmental regulations.
AB  - Releases of ammonia (NH3) to the atmosphere contribute significantly to the
      deposition of nitrogen to both terrestrial and aquatic ecosystems. This is the
      background for the national NH3 emission ceilings in Europe. However, in some
      countries the national legislation aims not only to meet these ceilings but also
      to reduce the atmospheric nitrogen deposition to local ecosystems. Such measures
      to reduce the load of nitrogen to local ecosystems were introduced in Denmark in
      1994. In this paper we demonstrate that this regulation is reflected in the NH3
      concentrations in Denmark. The Danish legislation forces farmers to applying
      manure to the fields during the crop-growing season. We have analyzed the
      seasonal variation in local NH3 concentrations over the time period of 1989-2003.
      During this period the seasonal variation has changed from having moderate spring
      and autumn concentration peaks to having a single and much more pronounced spring
      peak. In the analysis we apply an NH3 emission model to demonstrate that these
      changes in the seasonal variation are a result of the changes in the Danish
      legislation. The analysis demonstrates the strength of using a high-resolution
      emission model in the analysis of routine monitoring data.

PMID- 18817109
TI  - Dispersion modeling to compare alternative technologies for odor remediation at
      swine facilities.
AB  - The effectiveness of 18 alternative technologies for reducing odor dispersion at
      and beyond the boundary of swine facilities was assessed in conjunction with an
      initiative sponsored through agreements between the Attorney General of North
      Carolina and Smithfield Foods, Premium Standard Farms, and Frontline Farmers. The
      trajectory and spatial distribution of odor emitted at each facility were modeled
      at 200 and 400 m downwind from each site under two meteorological conditions
      (daytime and nighttime) using a Eulerian-Lagrangian model. To predict the
      dispersion of odor downwind, the geographical area containing the odorant sources
      at each facility was partitioned into 10-m2 grids on the basis of satellite
      photographs and architectural drawings. Relative odorant concentrations were
      assigned to each grid point on the basis of intensity measurements made by the
      trained odor panel at each facility using a 9-point rating scale. The results of
      the modeling indicated that odor did not extend significantly beyond 400 m
      downwind of any of the test sites during the daytime when the layer of air above
      the earth's surface is usually turbulent. However, modeling indicated that odor
      from all full-scale farms extended beyond 400 m onto neighboring property in the
      evenings when deep surface cooling through long-wave radiation to space produces
      a stable (nocturnal) boundary layer. The results also indicated that swine
      housing, independent of waste management type, plays a significant role in odor
      downwind, as do odor sources of moderate to moderately high intensity that
      emanate from a large surface area such as a lagoon. Human odor assessments were
      utilized for modeling rather than instrument measurements of volatile organic
      compounds (VOCs), hydrogen sulfide, ammonia, or particulates less than 10 microm
      in diameter (PM10) because these physical measurements obtained simultaneously
      with human panel ratings were not found to accurately predict human odor
      intensity in the field.

PMID- 18817110
TI  - The development of industry-specific odor impact criteria for feedlots using
      models.
AB  - Emissions from feedlot operations are known to vary by environmental conditions
      and few if any techniques or models exist to predict the variability of odor
      emission rates from feedlots. The purpose of this paper is to outline and
      summarize unpublished reports that are the result of a collective effort to
      develop industry-specific odor impact criteria for Australian feedlots. This
      effort used over 250 olfactometry samples collected with a wind tunnel and past
      research to develop emission models for pads, sediment basins, holding ponds, and
      manure storage areas over a range of environmental conditions and tested using
      dynamic olfactometry. A process was developed to integrate these emission models
      into odor dispersion modeling for the development of impact criteria. The
      approach used a feedlot hydrology model to derive daily feedlot pad moisture,
      temperature, and thickness. A submodel converted these daily data to hourly data.
      A feedlot pad emissions model was developed that predicts feedlot pad emissions
      as a function of temperature, moisture content, and pad depth. Emissions from
      sediment basins and holding ponds were predicted using a basin emissions model as
      a function of days since rain, inflow volume, inflow ratio (pond volume), and
      temperature. This is the first attempt to model all odor source emissions from a
      feedlot as variable hourly emissions on the basis of climate, management, and
      site-specific conditions. Results from the holding pond, sediment basin, and
      manure storage emission models performed well, but additional work on the pad
      emissions model may be warranted. This methodology mimics the variable odor
      emissions and odor impact expected from feedlots due to climate and management
      effects. The main outcome of the work is the recognition that an industry
      specific odor impact criterion must be expressed in terms of all of the
      components of the assessment methodology.

PMID- 18817111
TI  - Chemical-sensory characterization of dairy manure odor using headspace solid
      phase microextraction and multidimensional gas chromatography mass spectrometry
      olfactometry.
AB  - Livestock operations are associated with emissions of odor, gases, and
      particulate matter. The majority of previous livestock odor studies focused on
      swine operations whereas relatively few relate to dairy cattle. Identifying the
      compounds responsible for the primary odor impact is a demanding analytical
      challenge because many critical odor components are frequently present at very
      low concentrations within a complex matrix of numerous insignificant volatiles.
      The objective of this study was to describe a chemical-sensory profile of dairy
      manure odor using headspace solid-phase microextraction (HS-SPME) and
      multidimensional gas chromatography-mass spectrometry-olfactometry (MDGC-MS-O).
      Two analytical approaches were used: (1) HS-SPME time-series extractions (from
      seconds up to 20 hr) followed by gas chromatography-mass spectrometry
      olfactometry (GC-MS-O) analyses, and (2) relatively short HS-SPME extractions (30
      min) followed by MDGC-MS-O analyses on selected chromatogram heart-cuts. Dairy
      manure was collected at research dairy farms in the United States and Israel.
      Volatile organic compounds (VOCs) resolved from multiple analyses included sulfur
      containing compounds, volatile fatty acids, ketones, esters, and phenol/indole
      derivatives. A total of 86 potential odorants were identified. Of them, 17
      compounds were detected by the human nose only. A greater number of VOCs and
      odorous compounds were detected, as well as higher mass loading, on solid-phase
      microextraction (SPME) fibers observed for longer extractions with SPME. However,
      besides sulfur-containing compounds, other selected compounds showed no apparent
      competition and displacement on the SPME fiber. The use of MDGC-MS-O increased
      chromatographic resolution even at relatively short extractions and revealed 22
      additional odorants in one of the regions of the chromatogram. The two analytical
      approaches were found to be parallel to some extent whereas MDGC-MS-O can also be
      considered as a complementary approach by resolving more detailed chemical
      sensory odor profiles.

PMID- 18817112
TI  - Modeling studies of ammonia dispersion and dry deposition at some hog farms in
      North Carolina.
AB  - A modeling study was conducted on dispersion and dry deposition of ammonia taking
      one hog farm as a unit. The ammonia emissions used in this study were measured
      under our OPEN (Odor, Pathogens, and Emissions of Nitrogen) project over a waste
      lagoon and from hog barns. Meteorological data were also collected at the farm
      site. The actual layout of barns and lagoons on the farms was used to simulate
      dry deposition downwind of the farm. Dry deposition velocity, dispersion, and dry
      deposition of ammonia were studied over different seasons and under different
      stability conditions using the short-range dispersion/air quality model, AERMOD.
      Dry deposition velocities were highest under near-neutral conditions and lowest
      under stable conditions. The highest deposition at short range occurred under
      nighttime stable conditions and the lowest occurred during daytime unstable
      conditions. Significant differences in deposition over crop and grass surfaces
      were observed under stable conditions.

PMID- 18817113
TI  - Measurement, analysis, and modeling of fine particulate matter in eastern North
      Carolina.
AB  - An analysis of fine particulate data in eastern North Carolina was conducted to
      investigate the impact of the hog industry and its emissions of ammonia into the
      atmosphere. The fine particulate data are simulated using ISORROPIA, an
      equilibrium thermodynamic model that simulates the gas and aerosol equilibrium of
      inorganic atmospheric species. The observational data analyses show that the
      major constituents of fine particulate matter (PM2.5) are organic carbon,
      elemental carbon, sulfate, nitrate, and ammonium. The observed PM2.5
      concentration is positively correlated with temperature but anticorrelated with
      wind speed. The correlation between PM2.5 and wind direction at some locations
      suggests an impact of ammonia emissions from hog facilities on PM2.5 formation.
      The modeled results are in good agreement with observations, with slightly better
      agreement at urban sites than at rural sites. The predicted total inorganic
      particulate matter (PM) concentrations are within 5% of the observed values under
      conditions with median initial total PM species concentrations, median relative
      humidity (RH), and median temperature. Ambient conditions with high PM precursor
      concentrations, low temperature, and high RH appear to favor the formation of
      secondary PM.

PMID- 18817114
TI  - Back-trajectory analysis and source-receptor relationships: particulate matter
      and nitrogen isotopic composition in rainwater.
AB  - The southeastern portion of North Carolina features a dense crop and animal
      agricultural region; previous research suggests that this agricultural presence
      emits a significant portion of the state's nitrogen (i.e., oxides of nitrogen and
      ammonia) emissions. These findings indicate that transporting air over this
      region can affect nitrogen concentrations in precipitation at sites as far as 50
      mi away. The study combined nitrate nitrogen isotope data with back-trajectory
      analysis to examine the relationship between regional nitrogen emission estimates
      independent of pollutant concentration information. In 2004, the Hybrid Single
      Particle Lagrangian Integrated Trajectory (HYSPLIT) model was used to determine
      potential sources of nitrogen in rainwater collected at an urban receptor site in
      Raleigh, NC. The delta 15N isotope ratio signatures of each sample were used to
      further differentiate between sources of the rainwater nitrate. This study
      examined the importance of pollution sources, including animal agricultural
      activity, and meteorology on rainfall chemistry as well as the implications in
      fine particulate matter (PM2.5) formation. Samples that transited the dense crop
      and animal (swine) agricultural region of east-southeastern North Carolina (i.e.,
      the source region) had lower delta 15N isotope ratios in the nitrate ion (average
      = -2.1 +/- 1.7 per thousand) than those from a counterpart nonagricultural region
      (average = 0.1 +/- 3 per thousand.) An increase in PM2.5 concentrations in the
      urban receptor site (yearly average = 15.1 +/- 5.8 microg/m3) was also found to
      correspond to air transport over the dense agricultural region relative to air
      that was not subjected to such transport (yearly average = 11.7 +/- 5.8
      microg/m3).

PMID- 18817115
TI  - Evidence of enhanced atmospheric ammoniacal nitrogen in Hells Canyon national
      recreation area: implications for natural and cultural resources.
AB  - Agriculture releases copious fertilizing pollutants to air sheds and waterways of
      the northwestern United States. To evaluate threats to natural resources and
      historic rock paintings in remote Hells Canyon, Oregon and Idaho, deposition of
      ammonia (NH3), nitrogen oxides (NOx), sulfur dioxide (SO2), and hydrogen sulfide
      (H2S) at five stations along 60 km of the Snake River valley floor were passively
      sampled from July 2002 through June 2003, and ozone data and particulate
      chemistry were obtained from the Interagency Monitoring of Protected Visual
      Environments (IMPROVE) station at Hells Canyon. NH3 concentrations were high;
      biweekly averages peaked at 5-19 ppb in spring and summer and the nutrient-laden
      Snake River is a likely source. Fine particulate ammonium nitrate (NH4NO3)
      averaged 2.6 microg/m3 during the 20% of worst visibility days with winter
      drainage of air masses from the Snake River Basin and possibly long distance
      transport from southern California. Other pollutants were within background
      ranges. NH3 is corrosive to clay-based pictographs; nitrogen deposition can alter
      natural biotic communities and terrestrial ecosystem processes at levels reported
      here.

PMID- 18817116
TI  - Monitoring agricultural burning in the Mississippi River Valley region from the
      moderate resolution imaging spectroradiometer (MODIS).
AB  - The 2003 active fire observations from the Moderate Resolution Imaging
      Spectroradiometer (MODIS), on board NASA's Terra and Aqua satellites, were
      analyzed to assess burning activity in the cropland areas of the Mississippi
      River Valley region. Agricultural burning was found to be an important
      contributor to fire activity in this region, accounting for approximately one
      third of all burning. Agricultural fire activity showed two seasonal peaks: the
      first, smaller peak, occurring in June during the spring harvesting of wheat; and
      the second, bigger peak, in October during the fall harvesting of rice and soy.
      The seasonal signal in agricultural burning was predominantly evident in the
      early afternoon MODIS Aqua fire detections. A strong diurnal agricultural fire
      signal was prevalent during the fall harvesting months, as suggested by the
      substantially higher number (approximately 3.5 times) of fires detected by MODIS
      Aqua in the early afternoon, compared with those detected by MODIS Terra in the
      morning. No diurnal variations in agricultural fire activity were apparent during
      the springtime wheat-harvesting season. The seasonal and diurnal patterns in
      agricultural fire activity detected by MODIS are supported by known crop
      management practices in this region. MODIS data provide an important means to
      characterize and monitor agricultural fire dynamics and management practices.

PMID- 18817117
TI  - Air and groundwater pollution in an agricultural region of the Turkish
      Mediterranean coast.
AB  - Air pollution and groundwater pollution in conjunction with agricultural activity
      were investigated in Antayla province on the Turkish Mediterranean coast. The air
      pollution was investigated in terms of gas-phase nitric acid (HNO3), sulfur
      dioxide (SO2), ammonia (NH3), and particulate matter for a 6-month period in the
      atmosphere using a "filter pack" system, which was developed and optimized in our
      laboratory. Ozone was measured by using an automated analyzer. Among all of the
      gas-phase pollutants, HNO3 had the lowest concentration (0.42 microg x m(-3))
      followed by NH3. Agricultural activities seem to be the major source of observed
      NH3 in the air. The current state of water pollution was investigated in terms of
      organochlorine and organophosphorus pesticides around the greenhouses, in which
      mainly tomato, pepper, and eggplant are cultivated. Water samples were collected
      from 40 points, 28 of which were wells and 12 of which were surface water. The
      pesticide concentrations in water samples were determined by means of solid-phase
      extraction (SPE) followed by a gas chromatography (GC)-electron capture detector
      (ECD)/nitrogen phosphorus detector (NPD) system. In general, surface water
      samples were more polluted by the pesticides than groundwater samples. The most
      frequently observed pesticides were chlorpyriphos (57%) and aldrin (79%) in
      groundwater, and chlorpyriphos (75%), aldrin, and endosulfan sulfate (83%) in
      surface water samples. The highest concentrations were observed for fenamiphos
      (394.8 ng/L) and aldrin (68.51 ng/L) in groundwater, and dichlorvos (322.2 ng/L)
      and endosulfan sulfate (89.5 ng/L) in surface water samples. At least one
      pesticide had a concentration above the health limit in 38% of all the water
      samples analyzed.

PMID- 18817118
TI  - Use of random amplified polymorphic DNA markers to estimate heterosis and
      combining ability in tomato hybrids.
AB  - Random Amplified Polymorphic DNAs (RAPD) were used to estimate genetic distances
      and determine the correlation between genetic distance and hybrid performance of
      29 tomato lines that were the parents in a diallel mating design. Among 97
      observed bands, 69 showed polymorphism and were used for establishing genetic
      distances based on the Nei coefficient between parents. A UPGMA dendrogram and
      Multi-Dimensional Scaling (MDS) analysis based on Nei genetic distances clearly
      clustered each group, confirming the variation at a molecular level. Correlations
      between genetic distances of the parents and performances of hybrids were
      established for various quantitative traits. Significant correlations were found
      between RAPD markers estimated genetic distances and MPH, HPH, SCA for some
      traits. The low correlation between parental genetic distances and hybrid
      performances for some quantitative traits suggested that RAPD markers have low
      linkage to Quantitative Trait Loci (QTLs) or have inadequate genome coverage for
      these traits. The results indicated that RAPD markers can be used as a tool for
      determining the extent of genetic diversity among tomato lines, for allocating
      genotypes into different groups and also to aid in the choice of the superior
      crosses to be made among tomato lines, so reducing the number of crosses required
      under field evaluation.

PMID- 18817119
TI  - Characterization of midgut and salivary gland proteins of Hyalomma dromedarii
      females controlled by entomopathogenic nematodes.
AB  - Biological control of hard ticks, Hyalomma dromedarii (Acari: Ixodidae) using
      entomopathogenic nematode of two families; Heterorhabditidae and Steinernematidae
      was studied. The protective effect of controlled ticks including haemolymph and
      haemocytes against these biological agents were also investigated. It was found
      that heterorhabditid strains cause a higher effect in biological control of
      engorged female H. dromedarii than those of stienernematid strains. It induced
      mortality rates ranged from 12-92% versus 4-88% for stienernematid strains. It
      was also found that these entomopathogenic nematodes can not reproduce within the
      exposed ticks. SDS-PAGE of proteins extracted from midguts and salivary glands
      infected with 4000 IJs tick(-1) separated 21 and 25 protein bands versus 13 and
      19 protein bands from non-infected ones, respectively. It was concluded that
      entomopathogenic nematodes of family Heterorhabditidae proved to have a potential
      acaricidal effect in the control of hard ticks. Moreover, the controlled ticks
      released unknown proteins in their haemolymph that may promote the haemocytes to
      phagocyte the nematodes as a type of defense mechanism.

PMID- 18817120
TI  - An evaluation of water-yield relations in maize (Zea mays L.) in Turkey.
AB  - The objective of this study was to compare the responses of maize (Zea mays L.)
      to deficit irrigation. A field experiment was conducted during the 1999 and 2000
      growing seasons in western Turkey. Irrigation treatments were tested with 100,
      70, 50, 30 and 0% replenishment of water depleted at 120 cm soil profile from
      100% replenishment treatment at ten days intervals. The irrigation amount ranged
      between 0 and 323.20 mm in the first year and 0-466.61 mm in the second year of
      the experiment. Seasonal crop water use values were between 142.19 and 481.91 mm
      in 1999 and 136.25-599.45 mm in 2000. Average maximum and minimum yields were
      10639-10383 kg ha(-1) for full irrigated treatment (I100) and 3750-2136 kg ha(-1)
      for non-irrigated treatment (I0) in 1999 and 2000, respectively. Water deficit
      significantly affected maize yield. In both years, yield increased linearly with
      irrigation applied but the relationship varied from one year to the other. Water
      Use Efficiency (WUE) ranged from 1.49 to 2.71 kg m(-3), while Irrigation Water
      Use Efficiency (IWUE) varied from 1.44 to 2.55 kg m(-3) in both years. The yield
      response factor (ky) relating relative yield decrease to relative
      evapotranspiration deficit was found to be 0.99 for the data of the two
      experiments combined. Also, dry matter yields (DM) and leaf area index (LAI) were
      markedly affected by the irrigation treatments. The finding of this work showed
      that well-irrigated treatment should be used for maize grown in semi arid regions
      under no water scarcity.

PMID- 18817121
TI  - An identification in fish of the genus Puntius Hamilton 1822 (Cypriniformes:
      Cyprinidae) of some wetlands in northeast Thailand with the use of random
      amplified polymorphic DNA technique.
AB  - The experiment was carried out during the 2003 to 2006 at the Department of
      Fisheries, Khon Kaen University, Khon Kaen, Thailand in collaboration with the
      Department of Biosciences, the University of Hertfordshire, College Land,
      Hatfield, Herts, UK. Molecular RAPD technique was used for the determinations of
      DNA patterns of the fish genus Puntius Hamilton 1822. The fish samples of 1,500
      individual fish were collected from fifteen wetlands in Northeast Thailand and
      they were used for DNA extraction. Before the experiment was carried out the fish
      samples were morphologically identified and it was found that the collected fish
      consisted of 9 species i.e., Puntius altus, P. aurotaeniatus, P. binotatus, P.
      gonionotus, (e) P. leiacanthus, P. orphoides, P. partipentazona, P. schwanenfeldi
      and P. wetmorei. Genomic DNAs were extracted from 5 mg of muscle tissues
      (skeleton muscles) with the use of PUREGENE DNA Isolation Kit for Laboratory Use,
      Gentra Systems, USA. Eighty decamer primers from four kits were subjected to a
      preliminary test. It was found that only 10 decamer primers were most suited for
      this PCR amplification. The results showed that genetic distant values being
      established among and between pairs of the fishes of the 9 fish species ranged
      from 0.191 to 0.456 for a pair between Puntius gonionotus and Puntius altus and a
      pair between Puntius schwanenfeldi and Puntius leiacanthus, respectively.
      Similarity coefficient values within the 9 fish species ranged from 0.109 to
      0.231. The results on a Dendrogram of clusters showed that there were 5 minor
      groups of the 9 fish species but the 9 species could not be split or shifted into
      other genera of the fish due to small differences found within the values of
      similarity coefficients.

PMID- 18817122
TI  - Oxyeleotris marmoratus, predator or by-product in integrated aquaculture ponds.
AB  - Participating farms in the Muang district of Nong Khai Province, were selected
      for the investigation of management practices and yields of marble goby,
      Oxyeleotris marmoratus, in integrated culture with Nile tilapia (Oreochromis
      niloticus). The research took place from February to May, 2007. The observed
      production of O. marmoratus in integrated aquaculture ponds indicated a wide
      range of management practices. The yields of Oxyeleotris marmoratus were between
      22.1 to 316 kg ha(-1) (average 81+/-78 kg ha(-1)). The farmers tended to prefer
      Oxyeleotris marmoratus not only as a by-product, but also as the main product
      from their ponds. Most farmers realized that Oxyeleotris marmoratus predate Nile
      tilapia fingerlings from the natural spawning of mature Nile tilapia in the
      ponds. With respect to consumed prey, the frequency of occurrence of prawns was
      73.3%, whilst that of small fish was 43.3%. In terms of prey biomass, prawns were
      also the most abundant food item, giving the relative abundance of 56.0%. A
      preliminary trial on predation pressure was conducted to confirm the role of Nile
      tilapia fingerling as live feed for Oxyeleotris marmoratus in integrated
      aquaculture ponds and it was found that the daily predation pressure was between
      1.90 to 2.46 fish day(-1).

PMID- 18817123
TI  - Molecular characteristics of Anopheles maculipennis Meigen in Zanjan, north west
      of Iran, inferred from ITS2 sequence analysis.
AB  - The present study has been designed in order to verify the species composition
      within Anopheles maculipennis complex in North West of Iran. We determined
      ribosomal DNA sequences of the second internal transcribed spacer (ITS2) region
      from samples of Anopheles maculipennis Complex in Zanjan province. A total of
      1536 specimens within the Complex were tested by Multiplex PCR, only An.
      maculipennis was found in this area. One clone out of four different individual
      mosquitoes of each field was generated with ITS2 PCR and half of them (192
      samples) selected randomly for RFLPs. PCR-RFLP assay identified 2 haplotypes;
      haplotype I (99%) and haplotype II (1%). Twenty five sequences were generated
      comprising the 5.8S gene, the ITS2 and the 28S ribosomal gene. The alignment was
      422 in length and percentage of GC content was 50.3% (26.07% A, 23.59% T, 26.78%
      C, 23.7% G). The ITS2 was 290 bp in length and two haplotypes were revealed
      varying by a single base (T<-->C) at site 378. An. maculipennis is the dominant
      species anopheline of the province. ITS2 analysis revealed evidence of a slightly
      interaspecific variation among populations. However, further investigations on
      the genetic polymorphism among An. maculipennis populations and in particular
      within those belonging to the continental haplotype are required to support any
      hypothesis on differences in behavior across the distribution range for this
      potential malaria vector.

PMID- 18817124
TI  - Toxical effect of Peganum harmala L. leaves on the cotton leaf worm, Spodoptera
      littoralis Boisd and its parasitoids Microplitis rufiventris Kok.
AB  - The leaf extract and its fractions of Peganum harmala L. have shown pronounced
      mortal effect, decreased percent pupation and adult emergence of the cotton leaf
      worm, Spodoptera littoralis Boisd. The third instar larvae fed for two days on
      treated leaves were more susceptible to plant extract and its ethyl acetate and
      chloroform fractions. The active lowest concentration (5%) of the leaf fractions
      of P. harmala showed significant effect on the percentage of emerged adult
      parasitoids, Microplitis rufiventris Kok. GC/MS analysis showed the major
      constituent in ethyl acetate fraction was (23S) ethylcholest-5-en-3 beta-ol
      (28.04%) while those of chloroform fraction were hydroxyfuranocoumarin
      (Bergaptol) (15.68%), piperidinone (12.08%), thymol (11.82%), phosphoric acid,
      tributyl ester (9.80%) and trimethyl-nonenol (9.66%). The medicinal plant P.
      harmala could be carefully applied in integrated pest management due to its
      strong effect on cotton leaf worm pest.

PMID- 18817125
TI  - Mapping quantitative trait loci using the marker regression and the interval
      mapping methods.
AB  - The marker regression and the interval mapping methods were used for the
      detection of qualitative trait loci (QTL) in Arabidopsis thaliana in a cross
      between early flowering ecotypes Landsberg erecta and Columbia. The interval
      mapping method employs pairs of neighbouring markers to obtain maximum linkage
      information about the presence of a QTL within the enclosed segment of the
      chromosome, whereas the marker regression approach fits a model to all the marker
      means on a given chromosome simultaneously and obtains significance tests by
      simulation. The interval mapping method detected 22 QTL in seven traits and the
      marker regression method detected 22 QTL in six traits. The two methods detected
      sixteen QTL at similar positions of the Arabidopsis chromosomes and QTL for
      similar traits were localised to similar regions of the chromosomes and they
      showed similar mode of additive effect. This suggested that the two methods are
      similar in their QTL detection even though they employed different significant
      levels.

PMID- 18817126
TI  - The effect of the ground water of three different locations on some morphometric
      measurements of broiler chicken in Jeddah-Saudi Arabia.
AB  - In this study, the ground water from three different regions in Saudi Arabia;
      Hada El-Sham (G0), Om Al-Jood (G1) and El-Wazeria (G2) were tested to evaluate
      their suitability of using. For this purpose, the ground water were analysed and
      the physico-chemical characteristics were determined. The measured parameters
      were; pH, Total Dissolved Salts (TDS), Total Hardness (TH), Total Alkalinity
      (TA), cation (Na, K, Ca, Mg) and anion (NO3, SO4) concentrations. One hundred and
      currently from 21 day to six weeks broiler chicken were reared on the ground
      water of these locations and their morphometric measurements (body weight, feed
      and water consumption and feed assimilation) were recorded. From this study, it
      was noted that the ground water of G0 and G1 are very pure to be used in
      irrigation and drinking as they contain TDS less than 1100 ppm, whereas water of
      G2 cannot be used as the TDS value is 2650 ppm. However, the ground water of the
      three regions is not suitable for any kind of industry. Reared chicken in G0 were
      characterized by the highest growth rate despite of their lower rates of feed and
      water consumption. In G1, chicken had medium rates of growth and water
      consumption with higher rate of feed consumption. While chicken from G2 recorded
      the lowest growth rate and highest rate of water consumption due to the higher
      salt content of this water.

PMID- 18817127
TI  - Soil determinants for distribution of Halocnemum strobilaceum Bieb.
      (Chenopodiaceae) around Lake Tuz, Turkey.
AB  - In this study we aimed to reveal the ranges and effectiveness of soil parameters
      on the distribution of H. strobilaceum. Halocnemum strobilaceum Bieb. is a
      widespread species in saline habitats and the distribution pattern of this
      halophytic species around Lake Tuz in Central Anatolia was examined according to
      the soil characteristics. pH, electrical conductivity, soil humidity, salt
      percentage, soluble Ca2+, Mg2+, Na+, K+, CO3(2-), HCO3(-), Cl(-) and SO4(2-)
      values, total cations, cation exchange capacity, sodium adsorption ratio,
      exchangeable Na+, K+, Ca2+ and Mg2+ values were the examined soil properties. The
      most effective soil parameters for flowering period were found as Na, SO4, total
      cations, SAR and EC and for seed bearing period as EC, Mg, total cations, Cl, Na,
      SO4 and salt (%) content of the soil.

PMID- 18817128
TI  - Fibrinogen and ceruloplasmin in plasma and milk from dairy cows with subclinical
      and clinical mastitis.
AB  - The potential using of Acute Phase Proteins (APPs) in the assessment of mammary
      gland health was studied by examining the levels of Fibrinogen (Fb) and
      Ceruloplasmin (Cp) in plasma and milk from dairy cows with different grades of
      mastitis. Plasma samples were taken from jugular vein and milk samples were
      collected from quarters of cows with subclinical and clinical mastitis, as well
      as healthy controls. California Mastitis Test (CMT) were performed on each udder
      quarter of cows for detection of CMT2+ and CMT3+ quarters. CMT (0) and culture
      negative cases were considered healthy cows. Clinical mastitis, was graded as
      mild (clots in milk) or moderate (clots in milk and visible signs of inflammation
      in the mammary gland/s). The concentrations of Fb in the plasma of the cows with
      subclinical and clinical mastitis were higher than in the plasma of the healthy
      cows (p<0.01). There was no significant difference in plasma concentration of Cp
      between healthy and subclinical groups (p>0.05), but differences between clinical
      and healthy groups were significant (p<0.05). The concentrations of Fb and Cp in
      the milk of the cows with subclinical and clinical mastitis were higher than in
      the milk of the healthy cows (p<0.01). The results indicated that measurement of
      Fb in plasma and milk and Cp only in milk might be suitable for early diagnosis
      of mastitis in dairy cows.

PMID- 18817129
TI  - Trophic status and primary production in Lake Choghakhor, Chaharmahal-Bakhtiyari
      Province, Islamic Republic of Iran.
AB  - In this study, trophic state indicators, total phosphate, algal chlorophyll and
      Secchi disk transparency and zooplankton community of Lake Choghakhor was studied
      monthly between May 2003 and April 2004. This lake is a shallow ecologically and
      economically important water body in eastern part of Iran. Crop farming and
      recreational activities are examples of the human impact around and within the
      lake, leading to a loading of DIN (Dissolved Inorganic Nitrogen) and TP (Total
      Phosphate) into the lake. Now submerged plants especially Myriophyllum spicatum
      has covered almost the entire lake and dense macrophyte beds (Polygonom
      amphibium), located on the East Southern end of the lake appear to act as a sink
      for these nutrients. Lake Choghakhor appeared to be in a macrophyte dominated
      clear water state with low TP (annual mean: 24 +/- 15 microg L(-1)) and
      chlorophyll a (annual mean: 3 +/- 1.28 microg L(-1)) concentrations and very high
      Secchi depth. The grazing pressure of dominant pelagic filtering zooplankton
      Daphnia longespina did not seem to be significant in determining the low
      phytoplankton crop expressed as chlorophyll a. We expect that sequestering of
      nutrients by submerged plants and associated epiphytes are the dominant
      stabilizing mechanisms suppressing the phytoplankton crop of Lake Choghakhor.

PMID- 18817130
TI  - Digestion of rice straw and oil palm fronds by microflora from rumen and termite
      bacteria, in vitro.
AB  - The digestion and Volatile Fatty Acid (VFA) production from rice straw and oil
      palm fronds by cellulolytic bacteria isolated from the termite Coptotermes
      curvignathus were investigated. The bacteria were Acinetobacter strain
      Raminalimon, Enterobacter aerogenes strain Razmin C, Enterobacter cloacae strain
      Razmin B, Bacillus cereus strain Razmin A and Chryseobacterium kwangyangense
      strain Cb. Acinetobacter strain Raminalimon is an aerobic bacterium, while the
      other species are facultative anaerobes. There were significant differences
      (p<0.05) among the bacteria for Dry Matter (DM) lost and acetic acid production
      from rice straw and Acinetobacter strain Raminalimon showed the highest activity.
      The facultative bacteria C. kwangyangense strain Cb (cfu mL(-1) 231 x 10(-6), OD:
      0.5), E. cloacae (cfu mL(-1) 68 x 10(-7), OD: 0.5) and E. aerogenes (cfu mL(-1)
      33 x 10(-7), OD: 0.5) were used for digestion study with the rumen fluid
      microflora. The in vitro gas production technique was applied for the comparative
      study and the parameters measured were pH, gas (volume), dry matter lost, acetic
      acid, propionic acid and butyric acid concentrations. pH was not significantly
      (p<0.05) different among the five treatments. The bacterium C. kwangyangense
      strain Cb showed the highest activity (p<0.05) for DM lost, acetic acid,
      propionic acid and butyric acid production from rice straw when compared to the
      other bacterial activities. There was no significance (p<0.05) difference between
      the three bacteria for the dry matter lost of oil palm fronds but the production
      of Volatile Fatty Acids (VFA) was significantly (p<0.05) high in the treatment
      which was inoculated with C. kwangyangense strain Cb. The Gen Bank NCBI/EMBL
      accession numbers for the bacterial strains are EU332791, EU305608, EU305609,
      EU294508 and EU169201.

PMID- 18817131
TI  - Effects of oil pollution at Kuwait's Greater Al-Burgan oil field on the timing of
      morning emergence, basking and foraging behaviors by the sand lizard
      Acanthodactylus scutellatus.
AB  - An attempt was made to study the effects of oil pollution in a desert location
      (the Greater Al-Burgan oil fields, an area damaged in the second Gulf War) in
      Kuwait on the behaviour of the Sand lizard A. scutellatus. Polluted sites with
      apparently different degrees of contamination (namely tar mat, soot and clear
      sites) were compared with control areas outside this region. Between 2002 and
      2003, ten lizards (5 of each sex) on each polluted and each control site were
      observed in the field at a time of the year when they were highly active. Air,
      substrate and burrow temperatures were recorded and lizards were monitored for
      their morning emergence times, as well as their basking and foraging activities.
      The present study confirmed that the morning emergence times and the basking
      behavior varied in sand lizards among the different pollution site categories.
      Physical changes in the tar mat sites caused the substrate temperatures in these
      locations to rise more quickly in the morning in response to solar gain than was
      the case in the other sites. This gives lizards in these locations the
      opportunity to emerge earlier and to start eating more quickly, giving them an
      energetic advantage (perhaps, in turn, influencing their rates of growth and
      fecundity). The clear sites had the next earliest emergence and were the next
      hottest but it is difficult to account for this in terms of the physical
      characteristics of this site. The basking times were clearly shorter on the dark
      soot and tar mat sites that appeared to have higher solar gain than control or
      clear sites. There did not appear to be any obvious differences in foraging
      activity of lizards in the different locations. It appears that some aspects of
      simple behaviour in these lizards provides a reliable, noninvasive indices for
      assessing oil pollution in desert locations. The precise impact of these changes
      in these reptiles on their long-term viability needs to be evaluated.

PMID- 18817132
TI  - Practical methods for increasing light interception efficiency and root growth in
      soybean.
AB  - Determining the effect of different sources of nitrogen and weeds on two
      varieties of soybean, an experiment was conducted out at research station of
      Tabriz University, Iran. Treatments were two varieties (Williams and Harcor),
      four nitrogen levels (two levels of symbiotic bacteria and two levels of urea)
      and weeds (with and without control). Results showed that three various factors
      can significantly change the Photosynthetically Active Radiation (PAR) amount at
      different layers of canopy. Solar radiation decreased in a vertical profile of
      canopy because of increasing Leaf Area Index (LAI). At the bottom level of canopy
      only 6% of total arrived PAR was recorded. Increasing LAI caused a sharp decrease
      in Light Interception Efficiency (LIE) in the canopy. Weeds significantly
      affected root nodules in dry and fresh weights. So, in weedy condition of soybean
      canopy, accumulation of dry matter decreases due to decline in LIE. On the other
      hand, weeds can strongly affect on nodules activity and decrease potential of
      nitrogen fixation by symbiosis bacteria.

PMID- 18817133
TI  - Growth rates and milk production potential of Sahelian and Red Sokoto breeds of
      goats in northern Guinea Savannah.
AB  - The milk production potentials and growth rates of Red Sokoto and Sahelian goats
      fed basal diets of maize stover and Digitaria smutsii (wolly finger grass)
      supplemented with concentrate was investigated in two separate trials. In
      experiment 1, ten multi-parous does were allocated to intensive management
      following kidding. Does were hand-milked twice weekly and the milk production
      recorded. Body weight changes of dam and kid, milk fat, milk solid were
      determined weekly over 12 weeks period. The average birth weight of the Sahelian
      (2.2+/-0.23 kg) was significantly (p<0.05) higher than the Red Sokoto kids (1.0+/
      0.17). At weaning age, the average kid weight of the Sahelian (5.6+/-0.42 kg) was
      significantly higher than the Red Sokoto (3.9+/-0.44 kg). There was no
      significant difference (p>0.05) in daily milk yield and total lactation between
      the two breeds. The total solids and milk fat of 16.4+/-0.39 and 3.7+/-0.13% were
      significantly (p<0.05) higher for the Red Sokoto than the Sahelian (15.1+/-0.39
      and 3.2+/-0.13%). The second trial was to evaluate the comparative growth of the
      Sahelian and Red Sokoto breeds of goats. Animals were group-fed based on sex and
      fed Digitaria smutsii hay supplemented with concentrate. The growth trial lasted
      for 150 days with a 14 day digestibility trial. The Average Daily Gain (ADG) were
      significantly (p<0.05) different for breed, as well as sex. The Red Sokoto
      (66.9+/-1.59) kids had higher ADG than the Sahelian (46.6+/-1.59). Similarly the
      males of the Red Sokoto (61.9+/-1.59) had higher ADG than the Sahelian males
      (46.7+/-0.59) and the females of both breed. The experiments demonstrated a
      linear increase in weight gains of Red Sokoto over the Sahelian and a slightly
      higher milk yield obtained from the Sahelian providing the basis to conclude that
      the Sahelian goat can adapted and fit into the production systems of Sudan
      Savannah rural farmers.

PMID- 18817134
TI  - MR relaxivity measurement of iron oxide nano-particles for MR lymphography
      applications.
AB  - The aim of this study was to assess the T1, T2 and T2* relaxivity of Ultrasmall
      Super Paramagnetic Iron Oxide (USPIO) nano-particles in vitro and in vivo in rat
      models with magnetic resonance imaging at 1.5T. First, relaxation properties of
      USPIO nano-particles at different doses were measured using related SE and GRE MR
      imaging protocols. The relation between dose and relaxation were observed which
      is linear; Higher dose of the nano-particles means higher relaxivity. Based on
      this relation, an optimum protocol can be proposed for obtaining the best image
      contrast at each situation. Then detection ability of MRI protocols was studied
      for USPIO nano-particles with injection of the particles in the rat. The optimum
      MR protocols were used to observe the signal change of lymph nodes in rat.

PMID- 18817135
TI  - Obtaining of a symbiotic product based on lactic bacteria, pollen and honey.
AB  - This study presents the evolution of a Lactobacillus plantarum 2s strain and of a
      Lactobacillus acidophilus 1a strain on media containing pollen and honey. The
      following parameters were determined: CFU value, lactic acid production, sugar
      consumption and presentation of the final product. The researches were performed
      during 72 h, in tightly closed recipients, at a temperature of 37 degrees C,
      containing various quantities of milled or non-milled pollen (P1: 20 g non-milled
      pollen, 3 g honey, 5 mL distilled water; P2: 20 g milled pollen, 3 g honey, 5 mL
      distilled water; P3: 20% non-milled pollen, 3% honey; P4: 20% milled pollen, 3%
      honey). The media were very well homogenized before inoculation. The inoculation
      was made only after the medium gained a homogenous consistency. The inoculum
      consists of a 48 h culture of Lactobacillus plantarum 2s and Lactobacillus
      acidophilus, on LE medium, in equal proportions. The testing of the nutritive
      value of the symbiotic product was made on wistar rats, males and females,
      divided into lots of 10 animals each. The animals were administered symbiotic
      product every day, in their food, in intakes of 2 mg kg(-1) (lot I), 20 mg kg(-1)
      (lot II) and 200 mg kg(-1) (lot III), compared to a control. During the 4 weeks
      of the experiment, no lethality cases were recorded in any of lots, or in
      control. The animals involved in the experiment were examined daily and did not
      present changes of appetite, of behavior or clinical signs of disease.

PMID- 18817136
TI  - Characteristics, efficacy and safety testing of standardized extract of Croton
      tiglium seed from Indonesia as laxative material.
AB  - Identification and taxonomy analysis conducted at Herbarium Bogoriense at
      Research Centre for Biology, Indonesian Institute of Sciences Bogor. The name of
      the plant was C. tiglium L. The result of analysis on C. tiglium, ethanol extract
      as laxative material using the intestinal transit method showed treatment group
      that received dosage 0.06 mL/30 g b.wt. (72.5%) was significantly different
      compared to negative control (48.4%) or positive control (50.6%) which showed the
      weak effect as laxative at the dosage of 0.75 mL/30 g b.wt. It showed that
      ethanol extract of C. tiglium seed at dosage 0.06 mL/30 g is effective as
      laxative. The test result of the treatment using dosage 0.06, 0.04, 0.026 and
      0.07 mL/28 g of body weight showed the mice population response 100, 60, 40 and
      40% consecutively. The Thompson and Weil analysis result showed the ED50 was at
      0.027 mL or equal to 639,5 g kg(-1) b.wt. The LD50 was at 0.0707 equals with
      1674,5 mg kg(-1) b.wt. Safety limit is the range of dosage that cause the lethal
      effect and the dosage that gives the intended effect. The safety limit is
      represented by the comparison of LD50/ED50. Calculation result that the extract
      safety limit was LD50/ED50 = 0.0707/0.027 = 2.7.

PMID- 18817137
TI  - Plasma cortisol changes and body composition in Stizostedion lucioperca exposed
      to handling stress.
AB  - Stizostedion lucioperca aquaculture/stoking, remains a restrained industry due to
      several factors such as the paucity of freshwater resources and studies on the
      physiological responses of this species under environmental changes. The fish
      were subjected to handling stress by holding them out of the water in a hand-held
      dip net for 30 sec and netting the fish from the rearing tanks and transferring
      them to a small confinement tank. Sufficient aeration was supplied to the
      confinement tank to revert additional stress from oxygen depletion. Then measured
      changes in plasma cortisol levels and the growth ability (body composition) in
      Stizostedion lucioperca subjected to handling stress. Blood samples were
      collected from the fish after exposure to the handling stress. Crude protein
      (Nx6.25) was determined according to the Kjeldahl method, moisture content was
      determined by oven drying at 105+/-2 degrees C to constant weight and ash by
      heating in a muffle furnace at 550 degrees C to constant weight. Total lipids
      were extracted according to the Bligh and Dyer method. The results indicated
      that, handling stress significantly increased the plasma levels of cortisol 59.04
      ng mL(-1) versus 40.83 ng mL(-1) in control group. Also the decrease of the level
      of protein and lipid concentrations show a significant difference between
      treatment and control (p<0.05). As protein and lipid decreased, moisture
      increased from 78.19% in control to 80.40% in treatment groups. According to the
      results, there was no significant change in ash content in control and treatment
      groups which was about 9%. In other words, it could be emphasized that nutrition
      related behavior of Stizostedion lucioperca resulting from the activation of the
      hypothalamic/inter-renal axis in response to stress despite of different
      reactions bear resemblance to that of other fishes. Present data indicate that
      cortisol appears to be adequate to assess stress in Stizostedion lucioperca.

PMID- 18817138
TI  - Effects of different concentrations of bovine follicular fluid and estrous cow
      serum on development of murine 2-cell embryos.
AB  - Murine 2-cells embryos were isolated from murine oviducts at laboratory and
      transferred into Ham's F-10 medium containing 0.1 mg mL(-1) streptomycin and 100
      IU mL(-1) penicillin G and supplemented with 3 mg mL(-1) bovine serum albumin
      (BSA) or different concentrations of bovine follicular fluid (bFF) and estrous
      cow serum (ECS). Significantly higher (p<0.05) > or =4-cell embryos were
      developed when embryos were cultured 20% bFF (84.33%) comparing to 10 and 15% bFF
      (48.33 and 69.33%) as well as 3 mg mL(-1) BSA (65.66%). Morula rates were also
      lower in 10% bFF (22.33%) comparing to the other groups and were similar in 15
      and 20% bFF (62.66 and 72.33% morula rates) as well as BSA containing media
      (55.33%). The highest (p<0.05) blastocyst rates were obtained in medium
      containing 20% bFF (64.33%) and the lowest belonged to 10% bFF (15%) comparing to
      15% bFF (33.66%) or 3 mg mL(-1) BSA. When embryos were cultured in ECS, no
      significant different was observed in different culture media (76.66, 72.33, 82.5
      and 65.66% > or =4-cell embryos in 10, 15 and 20% bFF and 3 mg mL(-1) BSA,
      respectively). Morula and blastocyst rates were also similar in all groups
      (32.33, 41.66 and 66.25 and 55.33% morula rates and 15.33, 27, 44.50 and 29.66%
      blastocyst rates for 10, 15 and 20% bFF and 3 mg mL(-1) BSA, respectively). The
      results of the present study demonstrated that 20% bFF could be substituted for
      BSA when in vitro culture of murine embryos is carried.

PMID- 18817139
TI  - The effects of oral vitamin E on induction and consequence of experimental
      diabetes mellitus in rats.
AB  - Streptozotocin destroys the beta-cells of pancreas by generation of reactive
      oxygen species and vitamin E has documented antioxidant properties. To evaluate
      the preventive effect of vitamin E on induction of diabetes by streptozotocin and
      effect of oral vitamin E consumption on carbohydrate and lipid metabolism, forty
      male Wistar rats divided randomly to control, E1, E2 and E3 groups. The diet of
      E1, E2 and E3 groups were supplemented with 1, 2 and 4 g kg(-1) of vitamin E,
      respectively. Four days later all rats were made diabetic by IP injection of 45
      mg kg-' streptozotocin and blood glucose was measured 72 h later to determine the
      severity of blood glucose elevation. Glycosylated hemoglobin, triglyceride, total
      cholesterol and HDL-c were measured and LDL-c and VIDL-c calculated in plasma of
      6 diabetic rats with glucose more than 200 mg dL(-1) in each groups 21 days after
      streptozotocin injection. Vitamin E had no effect on diabetes induction by
      streptozotocin, but elevation of glycosylated Hb and reduction of LDL-c in group
      E3 were significant. Vitamin E also increased HDL-c although it was not
      statistically significant. We suggest that oral vitamin E consumption may have
      some beneficial effect on the correction of lipid metabolism disorders of
      diabetes, although it may worsen carbohydrate metabolism in mild diabetes.

PMID- 18817140
TI  - Effects of short and long term treatment of Ballota undulata on female albino
      rats fertility and pregnancy.
AB  - The objectives of this study is to investigate the toxic effects of Ballota
      undulata (300 mg kg(-1) b.wt.) on the reproductive system after administration to
      female Sprague-Dawley rats for two time periods 4 and 12 weeks. Forty adult
      female Sprague-Dawley rats were divided into two treatment and two control groups
      of 10 rats each. The two treated groups received 15 mg kg(-1) b.wt. of Ballota
      undulata for two periods of 4 and 12 weeks. Female rats were allowed mating with
      males after treatment. Several pregnancy parameters were investigated including:
      total number of pregnant rats, body weight and reproductive organ weight, number
      of implantation sites, number of resorption sites and number of viable fetuses.
      The significance of these results was calculated using student's t and Chi-square
      tests. Exposure to Ballota undulata for 4 weeks did not have significant effects
      on most parameters investigated. However, a slight decrease in the relative
      ovarian and embryo weights was observed. Administration of Ballota undulata for
      12 weeks significantly reduced the percentage of pregnancies and the number of
      implantation sites when compared with controls. In addition, a decrease in
      ovarian weights and in viable fetuses' number was also observed. Histological
      sections of ovaries of female treated with Ballota undulata were found to have
      congested blood vessels in cortical and medullary regions. We also noted the
      arrestment of developing follicles at primary and secondary stages in addition to
      presence of degenerative areas and hypercellullarity in medulla. Long term
      treatment with Ballota undulata might lead to diversified negative effects on
      fertility and pregnancy in female rats.

PMID- 18817141
TI  - Effects of yeast probiotic (Thepax) enrichment on biochemical parameters of A.
      urmiana nauplii.
AB  - Nauplii Artemia urmiana was enriched with Thepax--a commercial product containing
      yeast cells of Saccharomyces cerevisiae. The Thepax-induced changes in
      biochemical parameters such as crude protein, fat, fiber, ash and energy were
      determined in the nauplii enriched at different times (6, 12 and 18 h) after
      hatching. To identify these changes, each group of nauplii (6, 12 and 18 h post
      hatching) was enriched with 10(7) colony forming units (cfu mL(-1)) for a 24 h
      period. Enrichment with Thepax increased the ash content but decreased crude fat,
      protein and energy contents of Artemia urmiana nauplii (p<0.05). Thepax had no
      effects on crude fiber (p>0.05). As shown by the results of this study, it seems
      that probiotic enrichment with Thapax is favorable to improve the mineral (ash)
      content of Artemia urmiana nauplii. However, supplemented yeast probiotic with
      lipid emulsion and proteolytic enzymes is suggested for the nauplii enrichment.

PMID- 18817142
TI  - Evaluation of Bt (Bacillus thuringiensis) rice varieties against stem borer
      (Chilo suppressalis).
AB  - Three transgenic rice varieties namely Khazar, Neda and Nemat, all containing a
      cry1Ab gene, were evaluated through PCR analysis and field examinations for their
      resistance at natural infestation of insect pests during 2007. The results showed
      that all transgenic varieties produced 1.2 kb PCR product derived from
      application of cry1Ab gene. In field conditions, transgenic varieties exhibited
      high levels of resistance against natural infestation of stem borer and the
      damaged plants based on dead heart or white heat for them were less than 1%.
      Moreover, in stem-cut bioassay 100% of released larvae died within four days
      after infestation. These results demonstrate that expression of cry1Ab gene in
      the genome of transgenic varieties provided season-long protection from the
      natural infestation of lepidopteran insects.

PMID- 18817143
TI  - Selection of probiotic lactic acid bacteria isolated from fermented plant
      beverages.
AB  - Screening for probiotic bacteria from non-human sources were performed in this
      study. Three hundred and twenty-seven strains of Lactic Acid Bacteria (LAB) were
      isolated from 90 samples of Fermented Plant Beverages (FPBs) and pickles
      collected from around Thailand. Potentially useful probiotic properties were
      investigated in vitro in parallel with a commercial probiotic strain of
      Lactobacillus casei, R obtained from a dairy probiotic product in Thailand. An
      isolate SS2, selected from a fermented star fruit beverage, survived in the human
      biological barriers (0.15 and 0.30% bile salt, pH values between 3-8, presence or
      absence of oxygen), resistance to some antibiotics in general use and showed
      other benefits to the host (antibacterial activity, utilizations of protein and
      starch). The isolate SS2 had a higher specific growth rate and better inhibitory
      properties against food borne pathogenic bacteria and spoilage organisms than the
      commercial probiotic R strain. It also grew well in MRS and the SPY2 medium that
      is free from animal-derived ingredients, (r>0.8). The isolate SS2 was therefore
      considered to be a potentially useful probiotic LAB for a non dairy product such
      as FPBs and was provisionally identified as a strain of Lactobacillus plantarum.

PMID- 18817144
TI  - Ultrasonic studies on lamivudine: beta-cyclodextrin and polymer inclusion
      complexes.
AB  - The aim of the present study is to enhance the solubility and stability of drugs
      in addition of water-soluble polymer and carbohydrate complexes. The data show
      that the polymer polyvinyl alcohol (PVA) interacts with the free Lamivudine and
      with the Lamivudine; beta-cyclodextrin (beta-CD) inclusion complex, in both cases
      with particular intermolecular interaction was studied using ultrasonic technique
      under different concentrations at a temperature 303 K. Consequently, the reason
      of this study was to improve the biological performance of the drug through
      enhancing its solubility and stability. The binary and ternary mixtures prepared
      inclusion complexes of Lamivudine in beta-CD and PVA. The presence of PVA,
      changes the drug: beta-CD interaction, a Lamivudine: beta-CD: PVA complex was
      formed. In addition, the presence of PVA produces a strong increase in the
      binding constant at a particular concentration (1.25%). In the ternary complex,
      the Lamivudine is wrapped at both ends for the beta-CD. In this complex, the
      polymer seems to act as a bridge between both beta-CD molecules that bind the
      Lamivudine.

PMID- 18817145
TI  - Long term effects of one or two doses of hepatitis B vaccine in adults after five
      years.
AB  - The aim of this study is to evaluate hepatitis B vaccine protection in those
      adults who have taken one or two does of vaccine before. It was a retrospective
      cross sectional study was conducted on fifty-six military personnel in Tehran,
      Iran in the spring 2007. Demographic data such as age, marital status, education
      level, number of vaccine doses injected and, type of vaccine and date of last
      vaccination was collected. Their serum was tested for HBs Ab, HBc Ab and HBs Ag
      and finally the results were analyzed by SPSS software. All individuals were male
      with the mean age of 33.9+/-8.9 years. Twelve individuals who had only received
      one dose of injected vaccine had no antibody against HBsAg and no protection
      against hepatitis B virus. Of forty-four individuals that had received two doses
      of injected vaccine, 27 persons (61.4%) were protected and had serum HBsAb more
      than 10 MIU mL(-1). In conclusion one dose of HBV vaccine cannot produce immunity
      for five years but two doses of HBV vaccine can produce immunity for five years.
      However, HBsAb should be tested to make sure of immunity.

PMID- 18817146
TI  - Effect of salinity on growth and yield of Desi and Kabuli chickpea cultivars.
AB  - To evaluate the effects of different level of Na salinity (0, 3, 6 and 9 dS m(
      1)) on growth, yield and yield component of Kabuli (Hashem and Jam) and Desi
      (Kaka and Pirooz) chickpea cultivars a factorial experiment based on randomized
      complete block design with four replications was carried out in Research
      Greenhouse of Mokrian Agricultural Extension Center near Mahabad, Iran at 2006.
      Seeds of four chickpea cultivars were grown under 0, 3, 6 and 9 dS m(-1) levels
      of salinity until maturity. Salinity reduced the plant growth, flower, pod and
      seed number and seed weight. As increase in salinity, the undesirable effect of
      Na+ was more pronounced and reached the highest value at 9 dS m(-1) in all
      cultivars. Four chickpea cultivar have different responses to salinity and the
      Kabuli cultivars seemed to have a greater capacity for salt tolerance compared to
      Desi cultivars. Hahshem cultivar has the highest salinity tolerance among all
      cultivars.

PMID- 18817147
TI  - Effect of Metasystox-R on marine Nitrosomonas sp. as a nitrification inhibitor.
AB  - Metasystox-R is a systemic soluble liquid insecticide for the control of aphids
      on brassica vegetable crops, cotton and lupins and it is possible enter to the
      marine environment and may be have a hazard effects for the marine organisms and
      nitrification processes. Effect of Metasystox-R on ammonia oxidizing activity by
      marine Nitrosomonas sp. was investigated by determining nitrification inhibitor
      assay in the cell suspension. Results showed that 8 microg mL(-1) of Metasystox-R
      with PI50 = 4.48 significantly inhibited nitrite production by marine
      Nitrosomonas sp. These results suggested marine Nitrosomonas sp. may be one of
      the target bacteria which was inhibitor and decreasing nitrification in the
      marine environment.

PMID- 18817148
TI  - A method to study the effects of chemical and biological reduction of molybdate
      to molybdenum blue in bacteria.
AB  - In this research, we modify a previously developed assay for the quantification
      molybdenum blue to determine whether inhibitors to molybdate reduction in
      bacteria inhibits cellular reduction or inhibit the chemical formation of one of
      the intermediate of molybdenum blue; phosphomolybdate. We manage to prove that
      inhibition of molybdate reduction by phosphate and arsenate is at the level of
      phosphomolybdate and not cellular. We also prove that mercury is a physiological
      inhibitor to molybdate reduction. We suggest the use of this method to assess the
      effect of inhibitors and activators to molybdate reduction in bacteria.

PMID- 18817149
TI  - Effects of electron beam irradiation on dry matter degradation of wheat straw in
      the rumen.
AB  - The effect of electron beam irradiation at doses of 100, 200 and 300 kGy on
      ruminal dry matter degradation kinetics of wheat straw was investigated. Samples
      were irradiated by electron beam irradiator under identical conditions of
      temperature and humidity. Nylon bags of untreated or irradiated wheat straw were
      suspended in the rumen of three Taleshi steers for up to 96 h and resulting data
      were fitted to non-linear degradation model to calculate degradation parameters
      of dry matter. Results show that the washout fractions of dry matter increased
      linearly (p<0.001), but potentially degradable fraction and degradation rate
      decreased linearly (p<0.001) by electron beam irradiation. As a consequence, the
      effective degradability of dry matter increased linearly (p<0.001) with
      increasing irradiation dose. Electron beam irradiation at doses of 100, 200 and
      300 kGy increased the effective degradability of dry matter at rumen outflow rate
      of 0.05/h by about 7, 15 and 18%, respectively. In the condition of this study,
      electron beam irradiation at dose of 200 kGy appeared to be a suitable dose for
      improving dry matter degradability of wheat straw in the rumen.

PMID- 18817150
TI  - Effect of injecting with dexamethasone and progestagen-PMSG on reproduction and
      rearing of lambs in semi-intensive conditions.
AB  - The aim of the present study was to evaluate the effect of different doses
      dexamethasone and progestagen-PMSG on fertility and prolificacy in Kivircik ewes
      during the breeding season. For the experiment, 100 ewes were divided into four
      groups, with 25 females in each group. Groups were fluorgestone acetate (FGA, 30
      mg), administered via intravaginal sponges. Experimental groups 2, 3 and 4 mL
      dexamethasone injection were given 72 h before mating season. The fertility rates
      control, 2, 3 and 4 mL were 88.0, 92.0, 100.0 and 100.0%, respectively (p<0.05).
      The prolificacy rates for the same groups were 122.7, 130.4, 144.0 and 156.0%,
      respectively (p<0.01). The injections dexamethasone significantly increased lamb
      birth weight and daily weight gain for 60 days (p<0.05).

PMID- 18817151
TI  - Assaying of warfarin in Iranian warfarin resistance patients blood by HPLC.
AB  - A simple and rapid HPLC method with UV detecting system has been used in
      determination of warfarin level in plasma of Iranian patients who received
      different doses of this drug. Six resistance (10-70 mg day(-1)) and 5 sensitive
      patients (0.5-2.5 mg day(-1)) were selected for this study. Range of warfarin
      level in plasma was between 0.93 and 22.8. After determination of warfarin level
      in warfarin sensitive and especially, warfarin resistance patients, we are going
      to find a relationship between this level and pharmacokinetic or pharmacogenetic
      factors. In the separate study which was done in our laboratory on the gene that
      is possibly responsible for warfarin resistance we did not find any mutation in
      our patient with high warfarin concentration in their blood.

PMID- 18817152
TI  - Importance of seed-borne fungi of sorghum and pearl millet in Burkina Faso and
      their control using plant extracts.
AB  - Seed-borne fungi of sorghum and pearl millet in Burkina Faso were surveyed. A
      total of 188 seed samples from various locations, collected in 1989 (42) and 2002
      (146), were tested, using the blotter, dry inspection and washing methods.
      Infection experiments were carried out with the major fungi recorded on each crop
      by the blotter test. Six essential oils of plants were investigated for their
      inhibitory activity against eight pathogenic fungi. Thirty four and 27 fungal
      species were found in seed samples of sorghum and pearl millet, respectively.
      Phoma sp. and Fusarium moniliforme infected 95 to 100% of the seed samples of
      both sorghum and pearl millet. Sphacelotheca sorghi and Tolyposporium ehrenbergii
      were encountered in respectively, 75 and 33% of seed samples of sorghum. T.
      penicillariae, Sclerospora graminicola and Claviceps fusiformis were present in
      88, 41 and 32% of seed samples of pearl millet, respectively. Seeds inoculated
      with Acremonium strictum, Curvularia oryzae, F. equiseti, F. moniliforme and F.
      subglutinans and sown in sterilized soil, showed considerable mortality of the
      seedlings. Three essential oils inhibited in vitro the mycelial growth of all the
      fungi used by 85 to 100% and reduced significantly sorghum and pearl millet seed
      infection rates of Phoma sp., Fusarium sp., Curvularia sp., Colletotrichum
      graminicola and Exserohilum sp. Presence of many pathogenic fungi in considerable
      number of seed samples indicates the need of field surveys for these and other
      pathogens. Development of plant extracts for the control of seed-borne pathogens
      and public awareness on seed-borne diseases management measures for maintaining
      quality seed should be increased.

PMID- 18817153
TI  - Chemistry of groundwater of Al-Ahsa Oasis eastern region Saudi Arabia and its
      predictive effects on soil properties.
AB  - Saudi Arabia is an arid and the largest country in the middle east with a total
      land area of 2.253 x 10(6) km2. Recent urban and rural expansion has shown
      manifold increases in water use in various sectors. Water resources are limited
      and non-renewable coupled with unpredicted scanty rainfall. In order to meet the
      rising water needs, evaluation of water quality is important for allocation to
      various uses. A total of 101 well water samples were collected from Al-Ahsa
      Oasis. Water samples were analyzed for total salt concentration, pH, Ca, Mg, Na,
      K, HCO3, Cl, SO4, NO3, F and B contents. Soil Salinity Development (SSD),
      adjusted sodium adsorption ratio (adj.SAR), adjusted sodium adsorption ratio
      (adj. R(Na)) and Exchangeable Sodium Percentage (ESP) were calculated. The EC of
      groundwater ranged between 1.23 and 5.05 dS m(-1). Sodium was the most abundant
      cation followed by Ca, Mg and K in descending order. Chloride was the most
      abundant anion followed by SO4 and HCO3 in groundwater of Al-Ahsa Oasis. A
      significant correlation was found between Na and Cl (R2 = 0.936). Thermodynamics
      calculation revealed that an appreciable amount of Ca and Mg is associated with
      Cl and SO4 ions. The SAR and ESP values are within the permissible limits
      according to Ayers and Westcot, 1985. The NO3 concentration is within safe limits
      for drinking purpose according to WHO (1998) standards. The Saturation Indices
      (SI) indicated that groundwater is under-saturated (negative SI) with respect to
      certain minerals (for example: calcite, dolomite, gypsum, anhydrite, halite,
      pyrite, fluorite and aragonite) and oversaturated (positive SI) with respect to
      some other minerals (For example: Goethite, Siderite and hematite). The negative
      saturation index (SI) reveals that most of minerals are in un-saturated state and
      will dissolve more Ca and Mg into the soil solution after irrigation. A good
      relationship exists between Cl and other ions (Na, Ca and Mg) as well as between
      SO4 and Ca and Mg ion of groundwater. The salinity and sodicity hazards of
      groundwater of Al-Ahsa Oasis were classified as C3S1 and C4S2 i.e., high salinity
      with medium sodicity problems. The predicted soil salinity suggested application
      of 15-20% leaching requirements to keep soil salinity within permissible limits.
      Cultivation of slight to moderate salt and sodium tolerant crops is recommended
      for optimal agricultural production and efficient water use.

PMID- 18817154
TI  - Effects of cultural conditions on high temperature tolerance of Lentinula edodes
      mycelia.
AB  - The effects of several cultural conditions on high temperature tolerance of
      vegetative mycelia of five Lentinula edodes strains were investigated. Mycelium
      of longer culture age (70 days) was significantly shown high temperature
      tolerance compared to mycelium of shorter culture ages (14 and 30 days) for four
      strains, whereas SA142 that showed reverse. When the culture plates were
      pretreated at 30 and 33 degrees C for 48 h incubation before heat treatment (40
      degrees C, 8 h), mycelia of L. edodes strains were shown high temperature
      tolerance. Effects of nutritional factors in BM (basic medium) for the high
      temperature tolerance of L. edodes strains were also investigated. While yeast
      extract (as nitrogen source) and starch (as carbon source) were added to BM
      media, as a result cultured vegetative mycelia of L. edodes strains were
      significantly shown high temperature tolerance against heat treatment (40 degrees
      C, 6 and 8 h). Further more, addition of bases (adenine + cytosine), vitamin
      (biotin) and organic acid (tartaric acid) to BM media, consequently vegetative
      mycelia of some L. edodes strains were also effective to increase high
      temperature tolerance.

PMID- 18817155
TI  - Antioxidant activity of some Jordanian medicinal plants used traditionally for
      treatment of diabetes.
AB  - Medicinal plants are being used extensively in Jordanian traditional medicinal
      system for the treatment of diabetes symptoms. Twenty one plant samples were
      collected from different Jordanian locations and used for antioxidant evaluation.
      The level of antioxidant activity was determined by DPPH and ABTS assays in
      relation to the total phenolic contents of the medically used parts. The most
      frequently used plant parts as medicines were fruit, shoot and leaves. The total
      phenolic contents of methanol and aqueous extracts, from plants parts, ranged
      from 6.6 to 103.0 and 3.0 to 98.6 GAE mg g(-1) of plant part dry weight,
      respectively. DPPH-TEAC of the methanol extracts of plants parts were varied from
      4.1 to 365.0 mg g(-1) of plant dry weight versus 0.6 to 267.0 mg g(-1) in aqueous
      extracts. Moreover, the mean values of ABTS*- (IC50) varied from 6.9 to 400.0
      microg dry weight mL(-1) ABTS in methanol extracts versus 9.8 to 580.5 microg mL(
      1) in aqueous extracts. According to their antioxidant capacity, the plants were
      divided into three categories: high (DPPH-TEAC > or = 80 mg g(-1) ), (i.e.,
      Punica granatum peel, Quercus calliprinos leave, Quercus calliprinos fruit,
      Cinchona ledgeriana and Juniperus communis leave), moderate (DPPH-TEAC range 20
      80 mg g(-1)) (i.e., Salvia fruticosa shoot, Crataegus azarolus stem, Crataegus
      azarolus leave, Varthemia iphionoides shoot, Artemisia herba-alba shoot, Thymus
      capitatus shoot, Morus nigra leaves and Arum palaestinum leaves) and low
      antioxidant plants (DPPH-TEAC < 20 mg g(-1)), (i.e., Matricaria aurea shoot,
      Artemisia judaica shoot, Teucrium polium shoot, Pinus halepenss pollen grains,
      Sarcopoterium spinosum root, Crataegus azarolus fruit, Inula viscose shoot and
      Achillea fragrantissima shoot). The antioxidant activity of these plant's
      extracts and their potential rule in radical scavenging agreed with their
      potential use by Jordanian population as a traditional anti-diabetic agents.

PMID- 18817156
TI  - Randomized double blind comparison between sciatic-femoral nerve block and
      propofol-remifentanil, propofol-alfentanil general anesthetics in out-patient
      knee arthroscopy.
AB  - The aim of this study is the evaluation preparation and discharge times as well
      as the side-effects, patient satisfaction and costs after out-patient knee
      arthroscopy performed with a combined sciatic-femoral nerve block or a propofol
      remifentanil, propofol-alfentanil general anesthetics. Sixty patients,
      (remifentanil group 1, n = 20), (alfentanil group 2, n = 20) and a combined
      sciatic-femoral nerve block (PNB group 3, n = 20). In group 1, anesthesia was
      induced with remifentanil (1 mic kg(-1) followed by 0.5 mic kg(-1) min(-1) i.v),
      in group 2 alfentanil (20 mic kg(-1) followed by 2 mic kg(-1) min(-1) i.v, in
      both groups (group 1, 2) propofol was given 2 mg kg(-1) i.v followed by 9 mg kg(
      1) h(-1) i.v. Patients then received atracurium 0.6 mg kg(-1) i.v. to facilitate
      endotracheal intubation. In the PNB group (group 3), patients received a sciatic
      femoral nerve block with ropivacaine 25 mL 0.75 mg using a multiple injection
      technique aided by a nerve stimulator and a short, bevelled, Teflon-coated
      stimulating needle. There was no significant difference in the duration of stay
      in the post anesthesia care unit and day surgery unit between groups, there was
      significant increase in the time to first urination in PNB group than the other
      two groups. Also there was no significant difference in the stay in delay
      surgery. The cost of disposal materials, preoperative and post operative times
      were higher in PNB group. The cost of drugs was higher in remifentanil and
      alfentanil groups than PNB group; the total cost was insignificant in the three
      groups. In conclusion, this prospective randomized study suggests that in
      patients undergoing out-patient arthroscopy, a combined sciatic-femoral nerve
      block (using a small volume of ropivacaine 0.75%) compared with a propofol
      remifentanil or propofol-alfentanil general anesthetics techniques may provide
      similar intraoperative analgesic efficacy, a shorter length of stay in the PACU
      and an increased likelihood of bypassing the first phase of postoperative
      recovery.

PMID- 18817157
TI  - The use of principal component analysis in studying physical, chemical and
      biological soil properties in southern caspian forests (North of Iran).
AB  - This research was conducted in Khanikan forests located in lowland of Mazandaran
      province (North of Iran). Eighteen profiles were dug and several chemical,
      physical and biological soil properties were investigated. The soil properties
      evaluated were soil pH, bulk density, saturation moisture content, electrical
      conductivity, organic carbon, total nitrogen, cation exchangeable capacity,
      available phosphorous, soil texture, calcium carbonate content, number and
      biomass of earthworms, litter carbon and litter nitrogen. Principal Component
      Analysis (PCA) was used to identify the variation of soil properties. PCA, a
      technique which reduces the dimensionality of multivariate data by removing
      Interco relations among variables, has a number of useful applications in forest
      researches. The results showed significant relationships between some soil
      factors with PC1 and PC2 axes, also, among different soil factors, the
      distribution of forest types was most strongly controlled with some soil
      characteristics such as acidity, bulk density, texture, phosphorous, organic
      carbon, total nitrogen and cation exchangeable capacity.

PMID- 18817158
TI  - A survey on the faunal diversity of Savar Upazila, Dhaka, Bangladesh.
AB  - A survey was conducted during January to December 2006 to assess the status of
      faunal diversity of Savar Upazila, Dhaka, Bangladesh. A total of 30 species of
      birds, 24 species of winter birds, 7 species of reptiles, 3 species of
      amphibians, 15 species of mammalians and 32 species of fishes were recorded.
      Relative abundance of those species were determined. Of the birds, House Sparrow
      (Passer domesticus) was abundant while Blyth's Kingfisher (Alcedo hercules), Rock
      Eagle Owl (Bubo bengalensis), Hooded Pitta (Pitta sordida), Black-headed Oriole
      (Oriolus xanthornus), White-winged Duck (Cairina seululala) and Duck (Anser
      indicus) were rare. The relative abundance of winter bird could not be assessed
      because of their migratory habit. Striped keelback (Amphiesma stolata) and Common
      Smooth Water Snake (Enhydris enhydris) were very common while Black pond turtle
      (Geoclyms hamiltonii) and Pond tortoise (Melanochelys trijuga) were recorded as
      endangered. Common Toad (Bufo melanostictus) were abundant but Bull Frog (Rana
      tigrina) was rare. Asiatic Wild Dog (Cuon alpinus) and House Mouse (Mus musculus)
      were abundant while Common Otter, Large Indian Civet, Irrawaddy River Dolphin,
      Indian Hare were rare. Carpu, Silver carp, Tilapia, Nilotica were abundant while,
      Freshwater Garfish, One stripe spinyeel and Grey Featherback were rare.
      Landfilling, deforestation, poaching, industrial effluents and current jal were
      identified as major threats to the faunal diversity of Savar area.

PMID- 18817159
TI  - Restriction enzyme analysis and DNA sequencing comparison for alpha-toxin gene
      among different types of Clostridium perfringens.
AB  - Alpha-toxin is produced by all types of Clostridium perfringens. The genes
      encoding alpha-toxin from the available five types of Clostridium perfringens [A
      (chicken strain), A (rabbit strain), B, C and D] were PCR amplified using
      specific primers and the PCR products were examined on 1.5% (w/v) agarose gel and
      demonstrated the same bands comparable to the published alpha-toxin gene.
      Restriction enzyme analysis using two sets of enzymes (one set known to have
      recognition sites; Hinf1, EcoRV and Mse1 and the other set known to lack
      recognition sites Hind III, Pst1 and BamH1) were carried out. The first set of
      enzymes revealed the same cut specific for alpha-toxin gene. However, the second
      set of enzymes revealed no cut which is consistent to the published data. The PCR
      products of alpha-toxin gene from the five types were separately sequenced and
      aligned with all published alpha-toxin genes of Clostridium perfringens.
      Identities among all studied alpha-toxin gene sequences and with the published
      ones were nearly 96-98%. There are no any significant differences among these
      nucleotide sequences. It is concluded that alpha-toxin gene sequences among
      different types of Clostridium perfringens are similar and highly conserved.

PMID- 18817160
TI  - The effect of different hormones and incubation periods on in vitro proliferation
      of pineapple (Ananas comosus L.) Merr cv. smooth cayenne) shoot-tip culture.
AB  - Seven different hormone treatments, namely 6-benzylaminopurine (BAP) at 2, 3 mg
      L(-1) was applied singly and in combination with Indole Acetic Acid (IAA) at
      0.18, 0.8 and 1.8 mg L(-l), BAP at 3.3 mg L(-l) in combination with IAA at 1.8
      and 3.3 mg L(-l) and triple combination of BAP at 2.3, IAA at 1.8 and Gibberellic
      acid (GA3) at 1.0 mg L(-1) were tested, over four different incubation periods of
      30, 45, 60 and 75 days, for their effect in the proliferation and growth of
      Smooth cayenne pineapple shoot-tip culture. Combined application of BAP at 3.3
      and IAA at 1.8 mg L(-1) induced the highest proliferation of 19 shoots/explant
      and the highest total of 121 and 125 shoots over 4 cycles of multiplication.
      Raising the IAA to 3.3 mg L(-1) resulted in the lowest proliferation and stunted
      shoots. Incorporation of GA3 improved the shoot length but caused drastic
      reduction in proliferation. The other treatments showed an intermediate effect.

PMID- 18817161
TI  - Survival of Paramecium caudatum at various pH values and under normoxic and
      hypoxic conditions.
AB  - The objective of this study was to determine the survival of Paramecium caudatum,
      a protozoan ciliate, with different pH under normoxic and hypoxic conditions. P.
      caudatum was exposed to 18 treatments (in triplicate) of varying pH (4, 4.7, 5.7,
      6.7, 7.7, 8.7, 9.7, 10.7 and 11.7) with two different conditions of normoxic and
      hypoxic. Survival was examined every second day for three weeks. P. caudatum
      mortality was 100% immediately when exposed to pH 4, 10.7 and 11.7 either in
      normoxic or hypoxic conditions, whereas at other pH values tested this ciliate
      could survive mostly under hypoxic conditions. The results suggest that under
      hypoxic condition, 4.7-6.7 is the best pH range for survival of this species.

PMID- 18817162
TI  - Toxicological screening of lyophilized extract of some Nigerian wild mushrooms in
      mice.
AB  - Mushrooms are macrofungi widely consumed as food. However, many mushrooms rot
      away in the wild because of fear of toxicity. Therefore, lyophilized aqueous
      extracts of 6 mushroom species collected from Zaria, Nigeria and taxonomically
      identified as Chlorophyllum molybdites, Panaeolus subalteatus, Macrolepiota
      procera, Leucopaxillus albissmus, Hygrophoropsis aurantiacus and Pholiota aurea
      were screened for toxicity in mice. Lyophilized aqueous extract of each of these
      mushrooms was administered to three groups of 3 mice intraperitoneally (i.p.) at
      doses of 100, 1000 and 10, 000 mg kg(-1), respectively. Another group of three
      mice given distilled water served as control. The mice were examined for clinical
      signs of toxicity over a period of 72 h and pathological examinations conducted
      on dead animals. The severity of clinical signs, onset of death and pathological
      lesions were dose dependent. Death occurred within 10 min in all the mice dosed
      at 10,000 mg kg(-1) with the lyophilized extracts of all the mushrooms screened,
      with the exception of that of H. aurantiacus, which produced death 21-23 h post
      administration. This result showed that all the screened mushrooms, including the
      popular edible M. procera were found toxic. Therefore, since all the mushrooms
      screened were found toxic, it is recommended that extreme caution should be
      exercised in their consumption. Furthermore, in view of the regional differences
      in the toxicity of mushrooms, there is the need to screen more wild mushrooms
      found in Nigeria for toxicity. This will boost mushroom mycophagy, reduce
      poisoning incidence and reduce wastage of edible mushrooms in the wild.

PMID- 18817163
TI  - Histological assessment of Ghost crab's ovary (Ocypode saratan) in Chabahar Bay.
AB  - In this research, the histology of Flat crab's ovary (Ocypode saratan) is
      assessed in Chabahar Bay of Oman Sea during the period of December 2005 to
      December 2006. Ten ovaries of such species were sampled and fixed in the bouin
      solution. The samples were undergone the histology, preparation, dehydration,
      clearing and paraffination according to standard procedure. Then sections of 5
      micro were prepared and after coloration, they were studied under an electronic
      microscope. Gonad maturity stages of such species were determined in 6
      microscopic levels. In first and second stages, the crab is immature and third to
      sixth stages, the crab is mature. Oocyte diameter sizes in ovary through
      ovulation process are: Immature (< 20 microm), rudimentary (20-40 microm),
      developing (40-70 microm), intermediate (70-90 microm), advanced (90-160 microm)
      and resting (> 160 microm). Maximum dimension of oocyte frequency is 152.3 +/-
      0.5 micron. Salinity has complementary effect on temperature and increase in
      salinity results in complete maturityof gonads. Female sex has almost during May
      and September. The peak has been registered in May 4.12.

PMID- 18817164
TI  - Seasonal hair follicle cycle of Camelus dromedarius.
AB  - This experiment was conducted to identify the annual changes in hair follicle
      activity, changes at the follicular level and to characterize some of the fibre
      follicle characteristics of camels at different ages. A total of 28 camels were
      allocated at random on the basis of age to one of four groups (2, 4, 6 and older
      than 8 years). All groups of camels were fed a maintenance level of ration
      throughout the experiment. To determine hair follicle cycle and other follicle
      characteristics samples of skin were taken using a trephine from the right
      midside of animals at approximately 28 day intervals for a period of 12 months.
      Using a small hand clipper, 15 g of fibre sample was taken from the left midside
      region to determine fibre characteristics. Analysis of variance was performed
      using a one-way SAS package and the means and the standard deviations of means
      were generated with this program. Mean S/P ratio, primary and secondary and total
      follicle densities of all groups of camels were 6.85 +/- 0.75, 3.76 +/- 0.63,
      22.29 +/- 3.57 and 25.33 +/- 3.85, respectively. Mean fibre diameter, percentage
      of medullated and non-medullated fibre and clean wool percentage of all groups
      were 18.98 +/- 1.64, 18.10 +/- 1.65, 81.89 +/- 6.98 and 77.58 +/- 4.58,
      respectively. Mean percentage of active primary follicles significantly (p <
      0.05) decreased to lowest in February to a minimum of 83.1%, then significantly
      (p < 0.05) increased over spring. Secondary follicle activity decreased over
      winter and spring to a minimum of 60% in February.

PMID- 18817165
TI  - Effects of central histamine receptors blockade on GABA(A) agonist-induced food
      intake in broiler cockerels.
AB  - In this study, the effect of intracerebroventricular (i.c.v) injection of H1, H2
      and H3 antagonists on feed intake induced by GABA(A) agonist was evaluated. In
      Experiment 1, the animals received chloropheniramine, a H1 antagonist and then
      muscimol, a GABA(A) agonist. In Experiment 2, chickens received famotidine, a H2
      receptor antagonist, prior to injection of muscimol. Finally in Experiment 3, the
      birds were injected with thioperamide, a H3 receptor antagonist and muscimol.
      Cumulative food intake was measured 15, 30, 45, 60, 90, 120, 150 and 180 min
      after injections. The results of this study indicated that effects of muscimol on
      food intake inhibited by pretreatment with chloropheneramine maleate (p < or =
      0.05), significantly, while the famotidine and thioperamide were ineffective.
      These results suggest the existence of H1-receptor mediated histamine-GABA(A)
      receptor interaction on food intake in broiler cockerels.

PMID- 18817166
TI  - Epidemiology and antibacterial susceptibility patterns of bloodstream infections,
      2001-2004: an experience with BACTEC 9240 in Southern Iran.
AB  - This study was conducted to determine the prevalence of bacteria recovered from
      bloodstream samples by Bactec 9240 at our hospital wards and to evaluate their
      antibacterial susceptibility patterns. During January 2001 through December 2004,
      9407 referred blood samples in Bactec bottles from admitted patients at three
      main wards, neonates, pediatrics and adults at Nemazee Hospital, affiliated to
      Shiraz University of Medical Sciences in Shiraz were processed. Positive cultures
      were purified and identified according to standard methods. Sensitivity of
      bacteria to different antibiotics was determined by Kirby-Bauer disk diffusion
      method. Staphylococcus aureus 132(25%), Escherichia coli 64(12.1%) and
      Pseudomonas aeruginosa 52(9.8%) were the most pathogenic bacteria which were
      recovered from the blood samples. Pathogenic microorganisms were isolated from
      blood samples of 305 (57.8%) at pediatrics, from 181 (34.2%) at adults and from
      42 (8%) at neonates wards. The highest antibiotics activities against gram
      positive isolates observed for vancomycin (98.4%), chloramphenicol (86.4%) and
      ciprofloxacin (77.4%), while in gram negative bacteria imipenem (96.1%),
      ciprofloxacin (83%) and amikacin (77.9%), were effective antibiotics. Frequency
      of isolated bacteria at pediatrics compared to adults and neonates wards were
      approximately two and seven folds high, respectively which indicates special
      attention should be paid to pediatrics patients both in prevention and treatment
      aspects. Vancomycin and imipenim are the effective antibiotics and could cover
      majority of gram positive and negative bacteria. Therefore, combined
      administrations of these antibiotics seems mandatory for empirical therapy.

PMID- 18817167
TI  - Rapid detection of Salmonella enteritidis by PCR amplification of the SefA gene
      and it's cloning.
AB  - The emergence of Salmonella enteritidis as an important food-borne pathogenesis
      in humans, demands the development of novel detection and intervention
      strategies. It is generally accepted that fimbriae are an important factor in
      bacterial survival and persistence in the host. This study is directed towards
      the method of amplifying and cloning the SefA gene, which encode Salmonella
      enteritidis fimbrial protein. Strains used for these studies were S. enteritidis
      (E3), which were collected from Kermanshah region. Chromosomal DNA was extracted
      by boiling method and PCR reaction was performed and single band of 511 bp
      amplified by SefA-F and SefA-R primers. The resulting PCR product was inserted
      into the cloning vector (pTZ57R/T). In order to amplify the recombinant plasmid,
      E. coli DH5 alpha bacteria were transformed with SefA-pTZ57R/T. Recombinant
      clones were identified by blue/white selection and purified recombinant plasmids
      were indicated by an alkaline lysis procedure. Identity of the SefA-pTZ57R/T
      product was confirmed by RFLP and sequencing. Nucleotide and protein alignment
      with BLAST software showed that the sequence of the SefA gene derived from S.
      enteritidis (E3), which was cloned in the pTZ57R/T vector, was 99% identical to
      that of the Genbank (L11008). The sequence of the SefA gene from S. enteritidis
      (E3) differed only in two nucleotides and one amino acid. The cloned SefA gene
      from S. enteritidis (E3) was submitted to the NCBI Genbank (EF553334).

PMID- 18817168
TI  - The relationship between KCl infusion and changes of ECG, electrolytes of plasma
      and K content of donkey's red blood cells.
AB  - Sudden marked increases in the serum potassium concentration, up to 8 to 9 meq L(
      1), are the result of transcellular movement of potassium and are associated with
      profound electrocardiographic abnormalities and fluid shifts.
      Electrocardiographic changes associated with hyperkalemia have been described in
      the cat, the dog, the horse and are well documented in man. Since there is no
      research about the effects of hyperkalemia on electrocardiogram of donkey, the
      purpose of this study was to induce the experimentally hyperkalemia in donkey and
      studying the relationship between KCl infusion and changes of ECG, electrolytes
      of plasma and K content of donkey's red blood cells. This research was carried
      out in seven clinically healthy female donkeys, injected with 0.35 molar
      potassium chloride solutions to jugular vein. Results indicated that potassium
      content of RBC at 30, 45, 60, 75 and 90 min, blood potassium level at 30, 45, 60,
      75 and 90 min, blood calcium at 60, 75, 90 and 105, increased significantly and
      blood magnesium decreased significantly at 135 min. Electrocardiographic changes
      were first degree A-V block, wandering pacemaker, inversion of negative to
      positive T-wave, flattening of the P-wave, ventricular premature beat, sinus
      arrest, bradycardia and sinus tachycardia.

PMID- 18817169
TI  - Isolation of a novel mutated strain of Xanthomonas campestris for xanthan
      production using whey as the sole substrate.
AB  - This study was conducted to isolate novel lactose utilizing Xanthomonas
      campestris mutants. Such a mutant will assist the utilization of whey as the sole
      carbon source for xanthan gum production, lower costs of fermentation process and
      set a precise application for whey as a waste. In this study, a mutant strain
      (NA1) was isolated from Xanthomonas campestris cells exposed to nitrous acid
      mutagenesis Environmental conditions were optimized and maximum activity of the
      beta-galactosidase enzyme was obtained at pH 5.5 and 38 degrees C following which
      the beta-galactosidase activity in NA1 culture was increased 9.5 folds, compared
      to that of the wild type culture (336.1 U vs. 35.4 U). Xanthan gum production by
      NA1 using whey as carbon source was also studied. Using the experimental design
      of Plackett-Burman and statistical analysis, whey, as the main substrate and pH
      were the first factors affecting gum production among the seven parameters
      tested. Gum production using significant factors (such as substrate concentration
      and pH) was carried out in a lab-scale fermentor and 10 g L(-l) xanthan was
      obtained.

PMID- 18817170
TI  - Is there any association between overweight, obesity and symptoms of reflux
      disease?
AB  - The present study was aimed to identify the association of overweight and obesity
      with gastroesophageal reflux disease (GERD). This age- and sex-matched case
      control study was carried out in a sample of subjects referred to the specialized
      clinic of Tabriz University of Medical Sciences from November 2006 to March 2007.
      Data were collected using a demographic questionnaire and a checklist to
      determine reflux symptoms. Weight and height were measured and Body Mass Index
      (BMI) was calculated. Logistic regression was used to examine the association
      between overweight, obesity and reflux symptoms. The study population included
      106 cases (with reflux symptoms) and 111 controls with a mean age of 35.2 +/-
      12.9 years. The mean BMI was 2.4 units greater in cases than controls (p =
      0.0001). In unadjusted model, overweight (OR = 3.41, CI: 1.8-6.44) and obesity
      (OR = 2.84, CI: 1.38-5.82) were significantly associated with GERD. Results of
      multivariate logistic regression revealed significant association between
      overweight and GERD after adjusting for confounders (OR = 2.87, CI: 1.49-5.53).
      Given the increasing prevalence of patients with both overweight/obesity and
      GERD, Serious dietary intervention studies for weight loss as a therapeutic
      strategy should be carried out in GERD patients complicated with obesity.

PMID- 18817171
TI  - The distribution and coexistence of some wild plants in relation to mineral
      nutrient availability in a high sodium polluted site in central Sudan.
AB  - The factors affecting the distribution and coexistence of Cyperus laevigatus,
      Typha angustata and Paspalum viginatum, in a high sodium polluted site in central
      Sudan, were investigated. The high sodium content of the site was mainly due to
      effluents from a near by textile factory where high quantities of Na compounds,
      like: NaOH, Na2CO3, Na2SiO3 and NaHCO3 were used in the textile processes. The
      investigation was carried out by chemical analysis of soil and plant samples and
      computation of correlation coefficients between soil nutrients and ion uptake by
      the investigated plants. Soil and plant samples, from the investigated site, were
      collected from 35 sampling points of 80 x 120 m rectangular grid, each point is
      20 m distant from the other neighboring points. Soil chemical analysis data
      showed that the investigated site was moderately alkaline and characterized by
      very high content of Na, reasonably high content of Ca, adequate quantities of
      Mg, K and Fe, low content of NH4-N and P and very low content of Mn. The plant
      chemical analysis results clearly reflect the different nutritional requirements
      of the examined plant species. Correlation analysis between soil nutrients and
      ion uptake by the investigated plants showed that the uptake of a mineral ion by
      any of the three investigated plant species may be accelerated, slowed down, or
      may have no obvious effect by another ion in the soil. Moreover, correlation and
      regression analysis clearly reflect the different patterns of mineral nutrient
      uptake by the investigated species and hence niche differentiation and
      coexistence between the investigated species in the investigated site.

PMID- 18817172
TI  - Antioxidant activities of methanolic extract of Sapium ellipticum.
AB  - The stem bark extract of S. ellipticum (Hochst) Pax was investigated for its
      antioxidant properties in this study. The extract was evaluated for antioxidant
      activity in vitro in terms of its ability to inhibit lipid peroxidation and its
      free radical scavenging, reducing and metal chelation powers. The total amount of
      phenolic compounds in the extract was also determined in terms of gallic acid
      equivalent. The extract produced effective free radical scavenging and reducing
      activities in a dose dependent fashion. The extract exhibited noticeable
      inhibition of lipid peroxidation of linoleic acid emulsion. These activities were
      less than that of ascorbic acid and 2,6-Di-tert-butyl-4-methylphenol used as
      positive controls. The extract however demonstrated poor iron chelating ability
      compared to ethylene diamine tetraacetic acid. The total phenolic content of the
      extract was 50.61 +/- 0.08 mg g(-1) in terms of gallic acid. This study showed
      that the stem bark extract of S. ellipticum exhibits significant antioxidant
      activity and is a good source of natural antioxidants.

PMID- 18817173
TI  - Determination of soil conservation effects on shadow price of soil quality in dry
      farmed wheat in Iran (a case study).
AB  - This study attempts to measure the effects of soil conservation practices on soil
      quality in dry-farmed wheat in Iran (Zanjan province) using a bio-economic
      production function. Because of the nature of data (panel data) and information
      used in this study, error components approach (REM method) was used for
      estimating the production functions. The results indicate that the shadow price
      increases with soil depth and its magnitude is greater 72% in average--in
      conserved soils compared to non-conserved ones. In fact the results support the
      effectiveness of soil conservation in improving physical, chemical and
      biochemical properties of soil which contributes to sustainable agriculture.
      Finally, soil conservation benefits were estimated to be about 29.98 dollar pre
      hectare. That may be use for extension, payment of green subsidy, investment and
      adoption of new technologies for soil conservation. In this way, it will increase
      the real value of farm and farmer's welfare.

PMID- 18817174
TI  - The critical period of weed control in soybean (Glycine max (L.) Merr.) in north
      of Iran conditions.
AB  - A field study was conducted in 2006 at Sari Agricultural and Natural Resources
      University, in order to determine the best time for weed control in soybean
      promising line, 033. Experiment was arranged in randomized complete block design
      with 4 replications and two series of treatments. In the first series, weeds were
      kept in place until crop reached V2 (second trifoliolate), V4 (fourth
      trifoliolate), V6 (sixth trifoliolate), R1 (beginning bloom, first flower), R3
      (beginning pod), R5 (beginning seed) and were then removed and the crop kept weed
      free for the rest of the season. In the second series, crops were kept weed-free
      until the above growth stages after which weeds were allowed to grow in the plots
      for the rest of the season. Whole season weedy and weed-free plots were included
      in the experiment for yield comparison. The results showed that among studied
      traits, grain yield, pod numbers per plant and weed biomass were affected
      significantly by control and interference treatments. The highest number of pods
      per plant was obtained from plots which kept weed-free for whole season control.
      Results showed that weed control should be carried out between V2 (26 day after
      planting) to R1 (63 day after planting) stages of soybean to provide maximum
      grain yield. Thus, it is possible to optimize the timing of weed control, which
      can serve to reduce the costs and side effects of intensive chemical weed
      control.

PMID- 18817175
TI  - Molecular identification of Streptococcus equi subsp. equi and Streptococcus equi
      subsp. zooepidemicus in nasal swabs samples from horses suffering respiratory
      infections in Iran.
AB  - The objective of this study was to evaluate the existence of Streptococcus equi
      subsp. equi and Streptococcus equi subsp. zooepidemicus as probable agents
      associated with naturally occurring infection of the equine upper respiratory
      disease in Mashhad area. Nasal swabs samples from thirty horses with upper
      respiratory tract infections were collected. The bacteria isolated and identified
      were Streptococcus equi subsp. equi (1 isolate), Streptococcus equi subsp.
      zooepidemicus (25 isolates), Pasteurella sp. (11 isolates), Staphylococcus sp.
      (17 isolates), Bacillus sp. (4 isolates), Pseudomonas sp. (4 isolates), Proteus
      sp. (1 isolate), Neisseria sp. (1 isolate) and E. coli (1 isolate). All 25
      isolates of Streptococcus equi subsp. zooepidemicus and the isolate of
      Streptococcus equi subsp. equi were characterized by biochemical tests and
      molecular techniques. For molecular identification of the subspecies S. equi and
      S. zooepidemicus two genomic region SeM and sodA were amplified. This study is
      the first report of molecular identification of Streptococcus equi subsp. equi
      and Streptococcus equi subsp. zooepidemicus in Iran.

PMID- 18817176
TI  - Susceptibility of Sudanese Nubian goats, Nilotic dwarf goats and Garag ewes to
      experimental infection with a mechanically transmitted Trypanosoma vivax stock.
AB  - The present study was conducted to study the susceptibility of two different
      types of Sudanese goats namely: Black Nubian, the Nilotic dwarf goats and ewes of
      Garag type to experimental infection with Trypanosoma vivax stock isolated from
      cattle outside tsetse area. The infection caused parasitaemia, anaemia and
      pyrexia in the infected goats. However, the Nilotic dwarf goats were more
      tolerant to the infection than the Nubian goats, showing significantly higher
      values of packed cell volume, haemoglobin concentration, total red and white
      blood cells counts and significantly low parasitaemia and low body temperature.
      Garag ewes which were found to be susceptible to T. vivax infection showed
      different signs of anaemia and pyrexia; it is recommended that comparative
      studies on sensitivity of this type and other different Sudanese types of sheep
      to Trypanosomosis should be conducted.

PMID- 18817177
TI  - Nucleotide variability in the 5-enolpyruvylshikimate-3-phosphate synthase gene
      from Eleusine indica (L.) Gaertn.
AB  - This study reports the results of the partial DNA sequence analysis of the 5
      enolpyruvyl-shikimate-3-phosphate synthase (EPSPS) gene in glyphosate-resistant
      (R) and glyphosate-susceptible (S) biotypes of Eleusine indica (L.) Gaertn from
      Peninsular Malaysia. Sequencing results revealed point mutation at nucleotide
      position 875 in the R biotypes of Bidor, Chaah and Temerloh. In the Chaah R
      population, substitution of cytosine (C) to adenine (A) resulted in the change of
      threonine (Thr106) to proline (Pro106) and from C to thymidine (T) in the Bidor R
      population, leading to serine (Ser106) from Pro106. As for the Temerloh R, C was
      substituted by T resulting in the change of Pro106 to Ser106. A new mutation
      previously undetected in the Temerloh R was revealed with C being substituted
      with A, resulting in the change of Pro106 to Thr106 indicating multiple founding
      events rather than to the spread of a single resistant allele. There was no point
      mutation recorded at nucleotide position 875 previously demonstrated to play a
      pivotal role in conferring glyphosate resistance to E. indica for the Lenggeng,
      Kuala Selangor, Melaka R populations. Thus, there may be another resistance
      mechanism yet undiscovered in the resistant Lenggeng, Kuala Selangor and Melaka
      populations.

PMID- 18817178
TI  - Comparison of the performance, carcass characteristics and haematological
      parameters of broiler chicks reared in cage and floor.
AB  - This study was conducted to determine the effect of housing systems on the
      performance, carcass characteristics and the haematology of 150 four-week old
      Anak titan strains of broiler chicks in a completely randomized design. The birds
      were allocated randomly into two treatment (cage and floor) groups of three
      replications containing 25 birds per replicate. They were maintained for a period
      of 4 weeks and data were collected on; final body weight, weight gain, feed
      intake, feed:gain and mortality. At the 56th week, carcass yield, cut-up parts
      and organs weights as well as some parameters were measured. The results showed
      that feed intake and feed:gain were significantly (p < 0.05) higher in the cage
      system. Dressing percentage and breast weight were higher (p < 0.05) in the floor
      housing system while drumstick and lung weight were higher in the cage system. No
      significant (p > 0.05) difference was obtained in the haematology. It was then
      concluded that an improvement in the floor system could result into a better
      performance and an increased carcass yield.

PMID- 18817179
TI  - Presence of Aflatoxin M1 in raw milk at cattle farms in Babol, Iran.
AB  - In this study, raw cow milk samples were collected from milk churns at 40
      traditional and semi-industrial cattle farms located in Babol (Northern Iran) in
      winter 2006. In total, 120 raw milk samples were tested for Aflatoxin M1 (AFM1)
      contamination by competitive ELISA. In 68 out of 120 samples (56.7%) the presence
      of AFM1 was detected by concentration ranging from 50 to 352.3 ng L(-1). Fifty
      two samples (43.3%) contained AFM1 at levels of 4-50 ng L(-1) (The AFM1
      contamination levels were between 4-352.3 ng L(-1) by the average of 102.73 ng L(
      1)). In general, 56.7% of samples were beyond the limit of European community
      regulations (50 ng L(-1)). In other words, the AFM1 contamination levels in raw
      milk were more than twice over standard levels. The AFM1 contamination levels, (>
      50 ng L(-1)), in January, February and March were 40, 65 and 65%, respectively.
      Estimation of contamination of AFB1 using AFM1 in feed stuff showed that it was
      about 0.25 to 22 microg kg(-1) holding the average of 46.7%, being higher than
      European community limit (5 microg kg(-1)).

PMID- 18817180
TI  - Inhibitory effects of Sage extract on the growth of enteric bacteria.
AB  - Antibacterial activity of Sage extract at concentrations of 0.1, 0.05, 0.025,
      0.0125, 0.00625, 0.003125, 0.00156, 0.0005 and 0.00025 g dL(-1) against
      Salmonella typhi, Shigella sonnei, S. flexneri, Proteus vulgaris, Staphylococcus
      aureus, ETEC Escherichia coli and Pseudomonas aeruginosa was evaluated.
      Susceptibility testing of bacterial strains against 18 antibiotics was also
      performed for comparison. The results showed that P. aeruginosa and ETEC E. coli
      were completely resistant to Sage extract even at concentration of 0.1 g dL(-1).
      Its antibacterial activity (0.1 g dL(-1)) against P. vulgaris, S. flexneri and S.
      sonnei was the same as nitrofurantoin and ampicilline respectively. Sage extract
      (0.1 and 0.05 g dL(-1)) exhibited the same effects as ampicilline and
      streptomycin against S. typhi. Its antibacterial activity (0.1, 0.05 and 0.25 g
      dL(-1)) against S. aureus was the same as ceftazidim, chloramphenicol,
      gentamycin, neomycin and nitrofurantoin and was more significant compared to
      streptomycin and vancomycin. The results suggest Sage can be considered as an
      alternative herbal in the treatment of infections caused by the above-mentioned
      bacteria.

PMID- 18817181
TI  - Identification of the hyper accumulator plants in copper and iron mine in Iran.
AB  - The aim of present study was to identify accumulator plants that are effective
      for phytoremediation. We chose a mine of Iron and Copper named Hame Kasi that
      located western north of Hamedan city as a polluted area. In this region
      concentration of heavy metals is several times more than non-polluted area.
      Seventeen plant species and 6 soil samples were collected from this region for
      determination of heavy metals content. Atomic Absorption Spectrophotometer (AAS)
      was used for analysis of heavy metals in soil and plant samples, then tested
      plant species were grouped on the basis of their accumulation capability of heavy
      metals. The results of this research showed that there are some hyper accumulator
      plants in this area that can concentrate heavy metals in their different parts
      thus they can be used for remediation of polluted area.

PMID- 18817182
TI  - Ulcerative gingival granuloma: a condition for bone biopsy.
AB  - Osteomyelitis as a medical term defining a specific type of infection may be
      classified in acute and chronic form. In our case an acute mandibular
      osteomyelitis is reported with evaluation of the clinical and histological
      examination. The biological course of the disease determined on that basis. The
      significance of this report focused on the early diagnosis and the possible need
      for bone biopsy.

PMID- 18817183
TI  - Evaluation of a new CHROMagar medium for detection of methicillin-resistant
      Staphylococcus aureus.
AB  - Four laboratory methods including, E-test MIC, Oxacillin screen agar, manitol
      salt agar plus oxacillin and CHROMagar MRSA were compared for detection of
      methicilin resistant Staphylococcus aureus (MRSA). CHROMagar MRSA had a high
      sensitivity and specificity comparing to conventional E-test method. Sensitivity
      and specificity by manitol salt agar was 95 and 100%, respectively, while
      oxacillin screening agar method had 100% sensitivity and 95% specificity.

PMID- 18817184
TI  - Light and electron microscopic studies on the effect of a contraceptive drug on
      the stomach of mouse.
AB  - The present study was an investigation of the effect of the contraceptive drug,
      Nordette, on the stomach of the mouse when administered daily at a recommended
      therapeutic dose rate of 0.0026 mg kg(-1) for 30 days. Extensive light and
      electron microscopic changes were noticed. The drug caused enlargement in the all
      types of cells. The oxyntic cells appeared hypertrophied with irregular cell
      boundaries, enlarged nuclei and faintly stained cytoplasm. Their cytoplasm
      contained irregularly distributed mitochondria with dense matrix, decreased rER,
      obviously increased sER, disorganized intracellular canaliculi and some
      lysosomes. The peptic cells appeared enlarged and contained hypertrophied rough
      endoplasmic reticulum and an increase amount of ribosomes and secretory granules.
      There was an increase in the amount of the secretory granules in the lumen of the
      gastric gland. The mucus cells at the upper region of the gastric gland were
      greatly decreased. Smooth muscle fibers showed enlargement and degeneration. The
      submucosa and lamina propria showed vacuolation. The most pathological effects
      were restricted to the obvious decrease of the lymphoid cells in the submucosa
      and lamina propria. Dilatation and congestion of the blood vessels and blood
      capillaries were noticed. Blood capillaries lined by enlarged endothelial cells
      containing enlarged heterochromatic nuclei.

PMID- 18817185
TI  - Effects of salinity on survival, growth, reproductive and life span
      characteristics of Artemia populations from Urmia Lake and neighboring lagoons.
AB  - This study deals with effects of different salinities on the survival, growth,
      reproductive and lifespan characteristics of three Artemia populations from Urmia
      Lake and small lagoons at the vicinity of the lake under laboratory conditions.
      Experimental salinities ranged from 75 to 175 g L(-1). Salinity was proved to
      have significant impact on the majority of the characters studied in this survey.
      Growth and survival in bisexual A. urmiana and parthenogenetic Artemia from Lake
      Urmia were significantly higher with respect to the parthenogenetic Artemia from
      lagoons at most of the salinities tested. Reproductive characteristics such as
      total number of broods, total offspring number of offspring in each brood and
      number of offspring at each day of reproductive period reduced with increasing
      salinity. Moreover higher salinity prolonged the prereproductive period but
      shortened the total reproductive period. Higher salinities also affected the
      percentage of encystment and post-reproductive period, showing significantly
      higher values in parthenogenetic populations in comparison to bisexual A.
      urmiana.

PMID- 18817186
TI  - Effects of initial air removal methods on microorganisms and characteristics of
      fermented plant beverages.
AB  - The effects of 3 different methods for removing the initial air on the properties
      of fermented plant beverages produced from phom-nang seaweed (Gracilaria fisheri)
      and wild forest noni (Morinda coreia Ham.) were investigated. Only method M which
      covered the space above the fermentation liquid with a water filled plastic bag
      produced no surface film of yeast, had the highest acidity and also antibacterial
      activity from both plants after 90 days of fermentation. However, the yeast count
      still exceeded the standard guidelines for plant beverages. The fermented
      beverage from wild forest noni showed more antibacterial activity against 3 of 4
      pathogenic bacteria tested than that from the phomnang seaweed, probably for its
      higher levels of acidity and ethanol content. Lactic Acid Bacteria (LAB) isolated
      from the fermentation samples from days 1-5 using the method M from both
      fermented plant beverages were Leuconostoc mesenteroides supsp. mesenteroides and
      Leu. mesenteroides subsp. dextranicum while presence of Lactobacilus plantarum
      was only recorded at days 4-5 in the wild forest noni beverage. From days 6-14
      the isolates were Lactobacillus plantarum, Lactobacillus fermentum and
      Lactobacillus brevis from wild forest noni beverage, whereas only L. brevis was
      not detected in the seaweed beverage. During days 21-45 both beverages had a
      similar LAB population of L. plantarum and L. brevis while L. coryniformis was
      only found in the wild forest noni beverage. Between days 60-90 in both plant
      beverages only L. plantarum and Lactobacillius sp. were detected.

PMID- 18817187
TI  - Investigation of abundance and determination of dominant species of spider
      species in Iranian cotton fields.
AB  - In the present study, density of abundance of spiders explored and dominant
      species determined in the cotton major fields i.e., Ardebil, Fars, Golestan and
      Tehran provinces in 2003-2004. Through regular weekly, specimens collected by
      shaking bushes and they were carried out for the further study to the Araneae
      laboratory. A total of 632 specimens were classified in 76 species, 59 genera
      belonged to 19 families. Twenty seven species and 15 genera of them were new
      records for spider's fauna of Iran. The collected spiders counted and frequency
      of each species and dominant species determined. The following species Thanatus
      formicinus (Clerck), Cheiracanthium pennyi (O.P. Cambridge), Aulonia albimana
      (Walckenaer), Neoscona adianta (Walckenaer) were dominant species in Tehran,
      Ardebil, Fars and Golestan cotton fields, respectively.

PMID- 18817188
TI  - Comparison of heat shock response in Brucella abortus and Brucella melitensis.
AB  - Heat shock protein (hsp) is highly conserved, that serves a wide range of
      function in protein folding and transport. It protect from various type of stress
      including heat shocks. However, it is well known that the virulence of B.
      melitensis is more than B. abortus, but there is not any strong evidence to
      verify it. For this purpose, in refer to potent antigenicity of hsps in various
      infectious as well as some hsp molecules act as potent activator of macrophage
      (danger signal), we hypothesized that difference in virulence between B. abortus
      and B. melitensis may be originated from difference in pattern of response to
      heat shock induced by high degree of fever that usually present in brucellosis.
      To this end, five B. abortus and five B. melitensis strains isolated from cows
      and human, were subjected to 39, 40 and 42 degrees C heat shocks. The bacterial
      whole cell proteins were extracted and resolved by SDS-PAGE. Western blotting was
      used to detect antibody production against the extracted bacterial proteins
      especially hsp60 in both control and patient sera. SDS-PAGE gels revealed protein
      bands mainly in the range of 10-100 kDa. The amounts of a 60 kDa protein band
      (hsp60) was significantly enhanced following heat shock at 42 degrees C in
      relation to the unheated cells in both bacterial species. The heat shock
      responses in B. abortus and B. melitensis point to the higher production of a 60
      kDa protein (hsp60) in both bacterial species, especially in B. abortus. It seems
      that, lower hsp60 production by B. melitensis would induce a relatively much
      lower immune response against the bacterium leading to its greater virulence
      potentials; the sera from Brucellosis patients reacted with several of these cell
      derived protein bands in western blots, none of which were reactive with sera
      from healthy individuals. The western blot protein bands showed striking
      differences. This observation points to the immunogenic properties of hsps,
      specially the overwhelming response to hsp-60. Therefore, hsp-60 can be a good
      antigenic candidate for engineering subunit vaccine against Brucella, as well as
      for ELISA test development.

PMID- 18817189
TI  - Effect of shifting cultivation on distribution of nutrient elements and
      carbohydrates within water-stable aggregates in northern Iran.
AB  - This study attempts to evaluate the nutrient element and carbohydrate
      distribution within Water-Stable Aggregates (WSA) of two natural ecosystems,
      native forest and pasturelands, under different land uses. Soil samples were
      collected from depths of (0-20) cm in Typic Haploxeroll soils. The overall
      pattern indicated that Mean Weight Diameter (MWD) and WSA were greater in the
      pasture and forest soils compared with the adjacent cultivated soils and
      aggregates of > 1.0 mm size were dominant in the uncultivated soils, whereas the
      cultivated soils comprised aggregates of the size < or = 0.5 mm. Distribution of
      organic carbon, nitrogen, phosphorus and carbohydrates within the WSA showed
      preferential enrichment of these parameters in the macroaggregate fraction (4.75
      1.0 mm) for the uncultivated soils and microaggregate fraction (> 0.25 mm) for
      the cultivated soils. Average distribution of total exchangeable bases within WSA
      showed that cultivation of forest pastureland soils significantly led to reduce
      in these nutrient in the 4.75-2.0 mm fraction and increase in concentration of
      these cations in < 0.25 mm fraction. Since smaller aggregates are preferentially
      removed by erosion, this study emphasizes the need for sustainable soil
      management practices that they will minimize nutrient loss when forest or
      pastures lands are converted to cropland.

PMID- 18817190
TI  - Endo-parasitic helminthes of four mormyrid species (Osteichthyes: Mormyridae)
      from a West African flood river system.
AB  - Mormyrus rume rume, Hyperopisus bebe bebe, Campylomormyrus tamandua and
      Gnathonemus petersii sampled from the Anambra river with a fleet of gill nets,
      traps and hook and line were examined for endo-parasitic helminthes from October
      2005 to September 2006. Recovered helminthes were Rhadinorhynchus horridus from
      the intestine of H. bebe bebe and G. petersii; Procamallanus laeviconchus from
      the stomach of M. rume rume and C. tamandua; Spinitectus mormyri from the stomach
      of M. rume rume; Contracaecum sp. from the coelom of H. bebe bebe, G. petersii
      and C. tamandua, whereas an unidentified cestode infected the intestine of all
      the mormyrids. G. petersii constitutes a new host record for R. horridus; M. rume
      rume for S. mormyri and M. rume rume and C. tamandua for P. laeviconchus. In
      cases of mixed infection the parasites occupied their preferred habitats. The
      overall prevalence of the endo-parasites in the fish hosts was 41.9%, which is
      within the range (< 50%) typical of southern Nigerian freshwater lotic habitats.
      Prevalence, mean intensity and mean abundance of R. horridus in its host fishes
      were higher in the dry (October/November-March) than the rainy season (April
      September/October); in the nematodes (P. laeviconchus, S. mormyri and
      Contracaecum) the reverse was the case, whereas no definite pattern was exhibited
      by the unidentified cestode. P. laeviconchus appeared reddish from engorgement of
      blood but no damage was evident at the point of attachment. Local inflammation
      where R. horridus was attached to the mucosa of the intestine was not considered
      severe. R. horridus and P. laeviconchus are probably the most important parasites
      of the mormyrids in terms of fishery management in the Anambra river system.

PMID- 18817191
TI  - Purification and characterization of alcohol dehydrogenase from Gluconobacter
      suboxydans.
AB  - Purification and characterization of alcohol dehydrogenase (ADH) from
      Gluconobacter suboxydans was done in order to biotechnological and industrial
      application. Solubilization of enzyme from bacterial membrane fraction by Triton
      X-100 and subsequent fractionation on DEAE-Sephadex A-50 and Hydroxyapatite was
      successful in enzyme purification. Enzyme assay reaction mixture contained
      potassium ferricyanide 0.1 M, McIlvaine buffer 0.1 M (pH 5.5), Triton X-100 10%,
      ethanol 1 M and enzyme solution. The purified ADH Optimum pH activity was 5.5.
      The enzyme was in maximum stability in pH 5.8. The substrate specificity of the
      enzyme was determined using the same enzyme assay method as described above,
      except that various substrates (100 mM) were used instead of ethanol. The
      relative activity of the ADH for ethanol was higher than the others. The effects
      of metal ions and inhibitors on the activity of the enzyme were examined by
      measuring the activity using the same assay method as described above. Activity
      of purified enzyme was increased in the presence of Ca(+2) and was decreased in
      presence the of ethylenediamine tetra acetic acid (EDTA). Because the proper
      structure and function of the enzyme is related to structural Ca(+2) and EDTA can
      chelate Ca(+2). An apparent Michaelis constant for ethanol were examined to be
      1.7 x 10(-3) M for ethanol as substrate.

PMID- 18817192
TI  - Determining the uniformity coefficient and water distribution characteristics of
      some sprinklers.
AB  - The basic aim of the sprinkler irrigation method, as in other irrigation methods,
      is to apply irrigation water as uniformly as possible to the root zone. The
      uniform distribution of the applied water in sprinkler irrigation depends on
      factors such as sprinkler type, number and size of nozzles, arrangement of
      sprinklers, working pressure and the speed and direction of the wind. Sprinkler
      and lateral spacing should be determined by also taking the speed and direction
      of the wind into consideration. The aim of this study was to determine the
      application limits and the curves of water distribution under different working
      pressures, spatial arrangement and nozzle diameters under field conditions of
      some irrigation sprinklers which are widely used in Turkey. The objective was to
      determine the most appropriate system arrangement by using a computer program
      called CATCH3D. Five sprinklers were tested in the experimental area of Ondokuz
      Mayis University Campus and their water distribution characteristics identified.
      The most suitable operating parameters for Bereket 3: 12 x 18 m, Bereket 2: 12 x
      18 m, Egeyildiz 6 x 18m, Goktepe 6 x 12 m and for Atesler sprinkler 12 x 18 m
      arrangement type were determined.

PMID- 18817193
TI  - Using empirical equations to determine appropriate furrow length under field
      condition.
AB  - In this study, some of the empirical methods such as USDA-SCS and volume balance
      equations were used for determining furrow length. The main purpose was proving
      empirical equations application possibility. According to results, USDA-SCS and
      Volume Balance Equations can be used for determining furrow length at the Bafra
      Plain, Turkey. The field experiment and Volume Balance results are very close to
      each other. Experimental results are different from USDA-SCS equation results,
      but there is a relationship between both. There is a coefficient between field
      results and USDA-SCS equation result for furrow length. The coefficient (0.41)
      can multiply by UDSA-SCS result is 73 m which is very close to the field
      experimental result of 71 m.

PMID- 18817194
TI  - Effects of steckling weight and planting density on sugar beet (Beta vulgaris L.)
      monogerm seed yield and qualitative traits.
AB  - In order to determine the effects of steckling weight and planting density on
      sugar beet monogerm (Cv. 9597) seed quantitative and qualitative characteristics,
      this experiment was carried out in Ardabil Agricultural Research Station-Iran (38
      degrees 30'N and 48 degrees 30'E) during 2 years (2002-2003). In the study,
      steckling weight (main-plot) in three levels including 100, 100-200 and 200-300 g
      and planting density (sub-plot) in three levels including 40, 50 and 60 cm were
      used in a split-plot experiment based on the RCBD (Randomized Complete Blocks
      Design) with 5 replications. The measured characteristics were morphological and
      qualitative (velocity and uniformity of germination) characters, seed size
      distribution and monogerm seed percentage. According to the results of the
      experiment, the effect of planting density on the auxiliary branches No. and seed
      yield was significant at the probability levels of 1 and 5%, respectively. Seed
      yield increased by 43% as planting density was increased from 65 x 40 to 65 x 60
      cm. The increase in steckling weight led to the increase in standard seed portion
      (with 3.5-4.5 mm in diameter), germinable standard seed yield (11%) and decrease
      in germination velocity and germination uniformity; and increase in planting
      density was accompanied by increase in > 4.5 mm seed percentage, velocity and
      uniformity of germination and decrease in germinable standard seed yield.
      Eventually, the highest seed yield (1208 kg ha(-1)) was obtained by using
      steckling weight of 200-300 g and planting density of 65 x 60 cm.

PMID- 18817195
TI  - Impacts of fertilization systems on nitrogen loss and yield of oilseed rape
      (Brassica napus L.).
AB  - Farmyard manure is considered as a source of plant nutrient supply, but high N
      loss and low N use efficiency are often serious challenges facing this source of
      nutrient. It is supposed that a combination of manure with inorganic fertilizers
      can reduce this problem. A two year experiment was conducted in 2004-2005 at
      Mazandran province of Iran in order to study the effects of manure, inorganic
      nitrogen and combination of manure-inorganic nitrogen on N loss and yield of
      winter oilseed rape (Brassica napus L.) under rainfed conditions. Treatments
      included 0, 50, 100 and 150 kg N ha(-1) urea (F0, F50, F100, F150), 100 kg N ha(
      1) urea + 50 kg N ha(-1) manure (F100M50), 50 kg N ha(-1) urea + 100 kg N ha(-1)
      manure (F50M100), 150 kg N ha(-1) manure (M150). The highest grain yield (3 ton
      ha(-1)) was obtained with the 150 kg N ha(-1) as urea treatment in both years.
      Grain yield in M150 treatment was significantly lower (p < 0.05) than F150.
      However F100M50 and F50M100 resulted in similar yields compared with F150
      treatment. Results also showed that F100M50 and F50M100 treatments decreased N
      loss (4 and 3 kg N ha(-1) year(-1), respectively) compared to application of
      manure alone (33.5 kg N ha(-1) year(-1)) and F150 (36 kg N ha(-1) year(-1)).
      Overall, it could be conducted that F100M50 is the best treatment because it
      produced similar grain yield compared to F150 while resulted in lower N loss as
      well.

PMID- 18817196
TI  - Assessment of some soil properties by spatial variability in saline and sodic
      soils in Arsanjan plain, Southern Iran.
AB  - Spatial patterns for several soil parameters such soil texture, Exchangeable
      Sodium Percentage (ESP), Electrical Conductivity (ECe), soil pH, Cation Exchange
      Capacity (CEC) were examined in saline and sodic soils in Arsanjan plain,
      Southern Iran, in order to identify their spatial distribution for implementation
      of a site-specific management. Soil samples were collected from 0-30, 30-60 and
      60-90 cm soil depths at 85 sampling sites. Data were analyzed both statistically
      and geostatistically on the basis of the semivariogram. The spatial distribution
      model and spatial dependence level varied between soil parameters. Soil pH and
      ESP had the minimum and maximum variability at all depths, respectively. Soil
      properties indicated moderate to strong spatial dependence. ECe exhibited
      moderate spatial dependence at three depths; pH and ESP had a moderate spatial
      dependence at 0-30 cm and strong spatial dependence at 30-60 and 60-90 cm depths.
      Clay and CEC exhibited strong spatial dependence for the 0-30 cm and weak spatial
      dependence at 30-60 and 60-90 cm depths. Sand and silt had a non-spatial
      dependence at 0-30 cm and weak spatial dependency at 30-60 and 60-90 cm depths.
      The spatial variability in small distances of ECe, CEC, pH and ESP generally
      increased with depth. All geostatistical range values were greater than 1168 m.
      The results reported herein indicated that the strong spatial dependency of soil
      properties would lead to the extrinsic factors such as ground water level and
      drainage. It is important to know the spatial dependence of soil parameters, as
      management parameters with strong spatial dependence will be more readily managed
      and an accurate site-specific scheme for precision farming more easily developed.

PMID- 18817197
TI  - Hydrochemical processes and metal composition of Ain Umm-Sabah natural spring in
      Al-Hassa Oasis Eastern Province, Saudi Arabia.
AB  - This study was carried out to determine the hydro-chemical processes and the
      metal concentration of spring water to evaluate its suitability for irrigation
      and other purposes. A total of 10 water samples were collected from Ain Umm Sabah
      at different times and from different locations from the spring basin. EC (dS m(
      1)), pH, temperature, total cations (Na, Ca, Mg, K) and anions [Cl, CO3, HCO3,
      SO4, NO3, Fluoride (F)] were determined. Some trace and heavy metals (Al, As, Ba,
      B, Br, Mo, Ni, Si, Cd, Cu, V, Fe, I, Pb, Mn, Zn, Sr, Se, Sb, La and Se were
      determined. The Spring water is classified as C4S2 (high salinity with medium
      sodicity problem water). Chloride (Cl) and nitrate (NO3) concentrations were
      higher than the permissible limits according to World Health Organization
      Standards. The Ain Umm Sabah water is Na-Cl dominant water and can create soil
      sodicity problems and cause Na and Cl ion toxicity to plants if used for
      irrigation of sensitive crops. The spring water is under-saturated (negative SI)
      with respect to calcite, dolomite, gypsum, anhydrite, halite, fluorite and
      aragonite and oversaturated (positive SI) with respect to goethite, siderite and
      hematite minerals. The concentration of all the estimated trace metals was within
      the permissible limits for its use as drinking water and other purposes according
      to WHO. Since the spring water contains high concentration of NO3, hence can not
      be used for drinking purposes without prior treatment. The study findings suggest
      careful use and pumping of water from the spring. Further studies are required on
      regular basis to monitor the depletion in the spring water level and the temporal
      change in water salinity.

PMID- 18817198
TI  - Role of nitric oxide on the generation of atretic follicles in the rat ovaries.
AB  - The aim of this study was to investigate the role of Nitric Oxide (NO) in the
      atresia of ovarian follicles in an animal model. Twenty adult, female rats (90
      days old with body weights of210 +/- 10 g in the beginning of the experiments)
      were divided into 4 groups of 5 each. They were treated twice daily from the
      subcutaneous route for 21 successive days with either of the following chemicals:
      nitroglycerine, L-arginine, L-NAME, or saline. On day 22, all animals were
      sacrificed. Ovaries were dissected out free of connected tissue and were fixed in
      formaline 10%. Later, paraffine blocks were prepared and serial sections were
      made by means of H and E routine staining method. Intact and atretic follicles
      were counted separately. In addition, damages were analyzed qualitatively from
      the points of view of appearance and morphologic changes. In the evaluation of
      ovarian follicular structures, different types of healthy as well as atretic
      follicles were observed. In most of atretic follicles, the oocytes were
      abnormally elongated and increnation of their outlines were obvious. There were
      numerous macrophages around and inside of the atretic follicles. Our
      investigation regarding the distribution of atretic follicles in the ovaries of
      test groups revealed that atretic follicles in the L-NAME treated group were
      increased in comparison to the control group. Conversely, however, in the
      arginine-treated group, the atretic follicles were reduced compared to the
      control animals. Treatment with nitroglycerine of the rats decreased the number
      of atretic follicles significantly (p < 0.05) in comparison to the control group.
      In conclusion, enhanced NO, either from endogenous or exogenous origins, prevents
      atresia phenomenon, while inhibition of NO exerts an opposite effect.

PMID- 18817199
TI  - Callus induction and in vitro plant regeneration of rice (Oryza sativa L.) under
      various conditions.
AB  - The objective of the present study was to develop an effective protocol for
      optimum callus induction and complete plant regeneration for four varieties of
      rice (Oryza sativa L.) i.e., Super Basmati, Basmati-370, Basmati-371 and Fakhre
      Malakand. Calli were induced from mature seed scutelum. The Murashige and Skoog
      (MS) and Chu's N6 media containing hormone 2, 4-D (2, 4-Dichlorophenoxy acetic
      acid) in different concentrations were used for callus induction. Fakhre Malakand
      produced maximum calli on N6 media containing 3 mg L(-1) 2,4-D. while other three
      varieties showed maximum callus induction on N6 media containing 2.5 mg L(-1) 2,4
      D. N6 media was found better than MS media for callus induction. For complete
      plant regeneration the calli of two varieties i.e., Basmati-370 and Basmati-371
      were plated on N6 media containing different concentrations of NAA (1-Naphthalene
      acetic acid) and BAP (6-benzyl aminopurine). The maximum regeneration frequency
      (%) was observed on N6 media containing NAA 1 mg L(-1) and BAP 2.5 mg L(-1). It
      took 27-30 days for the callus to regenerate into a complete plant. Basmati-370
      produced 4-7 plantlets per callus whereas Basmati-371 produced 4-8 plantlets per
      callus with regeneration frequencies of 61 and 69%, respectively.

PMID- 18817200
TI  - Epidemiological aspects of Pediculosis capitis and treatment evaluation in
      primary-school children in Iran.
AB  - This study was undertaken to assess the prevalence of and epidemiological factors
      associated with, head lice infections in Iranian primary schools in 2006 and
      evaluate data on the therapeutic efficacy of lindane shampoo. A total of 40586
      children (19774 boys (48.72%) and 20812 girls (51.28%)] from 198
      Governmentprimary schools in Kerman, were screened for head lice between March
      and June 2006. The diagnosis of head lice infestation was confirmed by clinical
      inspection of scalp and hair for the presence of adult lice nymphal stage, or
      eggs (nit) by line-toothed head lice comb. All children infested with lice were
      treated with lindane shampoo (1% gamma benzene hexachloride). The overall
      prevalence of head lice infestation was 1.8%. The prevalence of infestation was
      significantly higher in girls (2.9%) than in boys (0.6%) (p = 0.000). The
      infestation rate was greater among pupils who were living in rural areas (4.6%)
      than in urban areas (1.5%). Of the 721 children with a positive examination
      result, 424 pupils (58.8%) were reported as having been infested with head lice
      in the previous 6 months. Mother's education level was a significant risk factor
      in this model (p < 0.05). At 2 weeks after the primary treatment, the success
      rates of treatment were 49%. Comprehensive survey in our work showed the better
      future of the disease and related factors. Education campaigns by health care
      officials, physicians and teachers are expected to be helpful for head lice
      control. It is essential that governments should be supported form cooperation
      between the school authorities and public health centers to successful control
      head lice infestation in primary school. Also there is an urgent need to identify
      safe, novel insecticides for proved efficacy.

PMID- 18817201
TI  - Investigation of the land subsidence and its consequences of large groundwater
      withdrawal in Rafsanjan, Iran.
AB  - Land subsidence is a phenomenon that involves the lowering or settling of the
      earth's surface due to various factors. The land subsidence due to groundwater
      withdrawal over the world has been seen in many areas. A decrease in ground water
      level would cause an increase in effective stresses at clay layers which results
      consolidation of lower layers. Since about 1980, it has been proven that Kerman
      Province subsidence in Iran is due to extensive ground water withdrawal.
      Overdraft of groundwater, an increasing of about 6 times since 1969 to 1999, has
      caused a decline of about 28 m in groundwater level. The rate of subsidence
      recently is about 5-15 cm. for decline of about one meter in groundwater level.
      In Rafsanjan area, many problems such as increase in the salinity of groundwater,
      land subsidence and consequently earth fissures and cracks in buildings are
      caused by groundwater withdrawal.

PMID- 18817202
TI  - Evaluating long-term annual sediment yield estimating potential of GIS interfaced
      MUSLE model on two micro-watersheds.
AB  - Use of an event scale MUSLE model for obtaining accurate long-term annual
      sediment yield estimates from micro-watersheds was evaluated. Such estimates are
      extremely important for designing appropriate soil/water conserving measures. For
      easy extraction and inputting of model input parameters, the proposed model was
      interfaced to an Arc-View/Spatial Analyst geographic information system.
      Application of this GIS interfaced MUSLE model on two gauged (pine and oak
      forest) hilly micro-watersheds viz., Salla Rautella (0.47 km2) and Naula (0.42
      km2), in Almora district of Uttaranchal, India showed that it could estimate
      annual sediment yields with absolute mean relative errors ranging between 12-14%.
      Even long-term average sediment yields for Salla Rautella (observed: 9.58 tons
      and estimated: 10.92 tons) and Naula: (Observed: 23.89 tons and estimated: 26.61
      tons) micro-watersheds could be quite realistically simulated by the proposed
      model.

PMID- 18817203
TI  - Utilization pattern of antibiotics in different wards of specialized Sari Emam
      University Hospital in Iran.
AB  - The main goal of this study was to compare the utilization of antibiotics in
      different wards of a university hospital. Consumption of antibacterial drugs rose
      dramatically during years 2000-2005 in Iran. Data collected during first half of
      year 2000 and 2005 in Emam University Hospital in city of Sari in Iran, showed
      use of antibiotics jumped from 95.4 DBDs (Defined Daily Doses per patient's bed
      days) to 124 DBDs. Distribution of different class of anti-microbial showed
      highest increase in use of vancomycin with 28.4 folds and clindamycin with 4.8
      fold. Use of cotrimoxazole, aminoglycosides and tetracyclines remained fairly
      unchanged during this period. However, during the same period, consumption of
      penicillin G, aminopenicillins and cloxacillin dropped 10.3, 3.8 and 3 fold,
      respectively. Among university hospital departments, oncology ward followed by
      ICU and general surgery consumed the most antibacterial agents in year 2000. In
      year 2005, ICU ward followed by gynecology, oncology and orthopedic were among
      the University Hospital Departments with highest consumption of antibiotics. The
      most highly used antibiotics in year 2000 were cefazolin followed by ampicillin,
      ceftizoxime and gentamicin. In year 2005, cefazolin, ceftriaoxone, gentamicin and
      ciprofloxacin were the most prescribed antibiotics. Injectable antibiotics
      accounted for 51.8 and 79.4% of total DBDs in first half of years 2000 and 2005,
      respectively. The bulk of prescription (90% of total DBDs) was made up of 13 out
      of 32 total antibiotic types in 2000 and 11 out of 29 total antibiotics types in
      2005. Comparing with similar hospitals in other countries, data presented show a
      dramatic increase in antibiotics prescribed by physician in Emam University
      Hospital.

PMID- 18817204
TI  - Estimation of genetic parameters on conformation traits of the Iranian Arab
      horses population.
AB  - Arab horse is a popular pure breed in Iran and is registered by World Arabian
      Horse Organization (WAHO). There is no scientific study and research about this
      breed. In this research 13 conformation traits on a random sample of the Iranian
      Arab horses studied. The estimate of variance components estimated by Animal
      Model and Derivative Free Restricted Maximum Likelihood (DF-REML) approach and DF
      REML software. Heritability of conformation traits is also evaluated. The range
      of estimated heritability were (0.050 +/- 0.008) neck length and (0.614 +/-
      0.087) croup height. Results indicated that, conformation traits were good traits
      for selection and horse genetic evaluation.

PMID- 18817205
TI  - Quantitative assessment of metals in local brands of tea in Pakistan.
AB  - In present study, Mn, Fe, Zn, Cu, Co, Pb, Cr, Ni and Cd were analyzed by FAAS in
      green and black tea samples of locally available in the Pakistani market. Na and
      K were also determined by Flame Photometer. Tea leaves can be the source of
      mineral components and trace elements, as well as some undesirable substances due
      to exposure to the environment. Among the metals tested, K was the most abundant
      one followed by Na, Mn and Fe. Fortunately, toxic heavy metals, Pb and Cd, had
      the lowest contents in tea samples and also in tea aqueous extracts.
      Concentration of heavy metals in tea aqueous extract was markedly lower than
      their total contents except that of K. The solubility of studied metals in tea
      aqueous extract varied widely and ranged from 0.0-95%. The lowest ranges of
      solubility were listed for toxic heavy metals Pb and Cd. The possible uptake of
      metals by the human body from tea aqueous extract has also been determined. The
      amounts of metals that one may take up through consumption of tea aqueous extract
      were found to match the acceptable daily intake even taking into account exposure
      from air, food and drinking water.

PMID- 18817206
TI  - Removal of sodium dodecyl sulfate in an intermittent cycle extended aeration
      system.
AB  - The objective of this study was to investigate the removal of an anionic
      surfactant from wastewater in ICEAS. The surfactant considered here was anionic
      SDS being widely used in the household and industrial detergents. Basic
      wastewater COD was 260 mg L(-1) and SDS surfactant added in range 20 to 400 mg L(
      1). The effect of the inlet SDS concentration and reaction time on COD and SDS
      removal was investigated. The results from this study indicated that the aeration
      time of 2 h was sufficient for removal of SDS ranged 20 to 400 mg L(-1). Obtained
      data showed low effluent SDS concentrations of 0.3 to 5 mg L(-1) and removal of
      SDS was more than 98%. These results revealed that biological treatment using
      ICEAS process is capable to treating wastewaters containing high concentration of
      SDS surfactant.

PMID- 18817207
TI  - Effects of dried and ensiled apple pomace from puree making on performance of
      finishing lambs.
AB  - This experiment was conducted to study the effect of ensiled and dried Apple
      Pomace (AP) obtained from puree making on finishing performance of lambs.
      Digestibilities of both ensiled and dried AP were determined using 4 mature
      sheep. In finishing experiment, 18 Sanjabi male lambs were used (9 per treatment)
      in a 120 day finishing experiment which was divided into two periods (60 day
      each). In the first period the ensiled AP and in the second period the dried AP
      were fed in an iso caloric, iso nitrogenous total mix ration. The Dry Matter
      (DM), crude protein and neutral detergent fiber of ensiled and dried AP were
      247.1, 63.85, 386.4 g kg(-1) DM and 888.4, 51.2, 385.6 g kg(-1) DM, respectively.
      No significant difference was observed in the apparent digestibility of ensiled
      and dried AP. The apparent DM digestibilities of ensiled and dried AP were 704.3
      and 668.2 g kg(-1) DM, respectively. Feeding ensiled AP significantly increased
      Dry Matter Intake (0.938 vs. 0.803 kg day(-1)), Average Daily Gain (ADG) (199.8
      vs. 155.56 g) and Feed Conversion Ratio (FCR) (4.69 vs. 5.16). Use of dried AP
      had no significant effect on DMI (1.030 vs. 0.932 kg day(-1)) but significantly
      improved the ADG (192.3 vs. 123.82 g) and FCR (5.36 vs. 7.52). Apple pomace
      increased carcass dressing percentage but had no effect on the percentage of
      different cuts. Results of this study suggest that AP, in both ensiled and dried
      forms, can improve the performance of finishing lambs.

PMID- 18817208
TI  - Prevalence of human immunodeficiency virus and hepatitis B virus in preoperative
      patients: potential risk of transmission to health professionals.
AB  - The aim of present study was to determine the prevalence of Human
      Immunodeficiency Virus (HIV) and Hepatitis B Virus (HBV) infections in
      preoperative patients admitted for surgical procedures at the Lagos University
      Teaching Hospital (LUTH), Lagos, Nigeria. Two hundred patients (200 samples
      tested for HIV) and (100 samples tested for HBV) comprising 90 males (45%) and
      110 females (55%) were recruited into the study. Sixty-eight of the 200 patients
      (34%) were scheduled for emergency surgery (group A) and 132 (66%) listed for
      elective surgery (group B). Seven (3.5%) of the 200 patients tested positive for
      HIV-1 and 2 using the Well-coenzyme method. Five (2.5%) and 2 (1%) of the 200
      patients confirmed HIV-positive were females and males respectively. Sixty-one
      percent of the 100 patients tested for hepatitis B surface antigen were males and
      39 (39%) females. Eighteen percent of the 100 patients examined were positive for
      (HbsAg). Ten percent of the 18 HBsAg-positive patients were males and 8 (8%) were
      females. This study showed the prevalence rate of HIV and Hepatitis B in
      preoperative patients at the Lagos University Teaching Hospital and to some
      reflects the prevalence of HIV and HBV in the general population.

PMID- 18817209
TI  - Races of Phytophthora sojae in Iran.
AB  - Phytophthora root and stem rot of soybean is a destructive disease of soybean in
      Iran. Races 1 and 3 of pathogen have already been reported from two major growing
      regions of the crop, Lorestan and Golestan provinces. In a survey during 2004
      2005, 142 isolates of P. sojae were recovered from infected plants and naturally
      infested soil samples using selective media and soybean leaf baiting technique.
      The majority of tested isolates (110 isolates) belonged to race one of P. sojae
      and 32 isolates belonged to race 3. ITS region of 23 isolates were amplified with
      specific primers Ps1 and Ps2. Sequences of this regions were similar to other
      gene banks sequences except two isolates from China. This survey showed low
      diversity in Iranian population of P. sojae.

PMID- 18817210
TI  - Effects of ovariectomy or orchidectomy and estradiol valerate or testosterone
      enanthate replacement on serum insulin in rats.
AB  - Various clinical observations and experimental data from in vitro studies suggest
      that insulin and sex hormones interact. The main purpose of the present study was
      to examine the effects of testosterone and estradiol on serum insulin in rats.
      Seven week old male and female albino (Wistar) rats were used in our study.
      Testosterone enanthate (50 mg kg(-1) day(-1)) or estradiol valerate (200 microg
      kg(-1) day(-l)) were injected intraperiotenally or subcutaneously in
      orchidectomised or ovariectomised rats, respectively. In orchidectomised rats,
      serum insulin was decreased compared with control animals (p < 0.01), on the
      other hand, decreasing of serum insulin was prevented by testosterone replacement
      (p < 0.001). In ovariectomised rats, serum insulin was also decreased compared
      with control group (p < 0.01) and decreasing of serum insulin was prevented by
      estradiol replacement (p < 0.05). Conclusively, present findings indicated that
      testosterone or estradiol were serum insulin enhancer hormones in male or female
      rats, respectively.

PMID- 18817211
TI  - Pedipalps and venom vesicle anomalies in two families of scorpions (Scorpiones:
      Hemiscorpiidae, Buthidae) from Iran.
AB  - The developmental anomalies are reported in this study. The first and second
      abnormally are presented in right pedipalps of Paraorthochirus and Orthochirus
      (Buthidae) while Paraorthochirus pedipalp just includes coxa, trochanter and
      without other parts (femur, patella, movable and fixed finger). The right
      pedipalp of Orthochirus specimen has abnormally too; it has all parts ofpedipalp
      except complete fixed finger. In both of scorpions, the left pedipalp is normal.
      Another case is present in venom vesicle of Hemiscourpius (Hemiscorpiidae).
      Pictures and morphometric measurements for three specimens are given.

PMID- 18817212
TI  - The effect of curcumin (active substance of turmeric) on the acetic acid-induced
      visceral nociception in rats.
AB  - In the present study, the effect of chronic oral administration of curcumin in
      the presence or absence of morphine and noloxone was investigated on the visceral
      nociception induced by acetic acid in rats. Intraperitoneal injection of acetic
      acid (1 mL, 2%) produced contractions in the abdominal musculature (writhes). The
      latency time to the beginning of the first writhe was measured and the total
      number of writhes in the 1 h after acetic acid injection was counted. The latency
      time to the beginning of the first writhe was significantly (p < 0.05) increased
      and the number of writhes was significantly (p < 0.05) decreased by curcumin (20
      and 40 mg kg(-1) body weight). The same results were obtained after subcutaneous
      injection of morphine (1 mg kg(-1) b.wt.). Naloxone at the dose of 1 mg kg(-1)
      body weight had no effect on pain intensity. Curcumin significantly (p < 0.05)
      enhanced the effect of morphine on the visceral pain responses, however did not
      reverse the effect of naloxone. Present data suggest that in the acetic acid
      induced visceral nociception of rats, curcumin may produce an antinociceptive
      effect and the endogenous analgesic opioid system is involved in the curcumin
      induced antinociception.

PMID- 18817213
TI  - On the Indian crested porcupine, Hystrix indica (Kerr, 1792) in Turkey (Mammalia:
      Rodentia).
AB  - This study presents some data about ecological, biological and taxonomical
      characteristics of Hystrix indica (Kerr, 1792) from Turkey. For this purpose
      characteristics of burrow, skull, tooth and measurements of external and cranial
      characters of two female H. indica from Turkey were investigated. It was
      concluded that our specimens are between the Middle East and Indian sub-region
      specimens in terms of morphometrical. It was also determined that there were
      roots in stomach contents of specimens.

PMID- 18817214
TI  - Effect of season on the immunity of newly hatched broiler chicks reared in arid
      hot climate.
AB  - This study was conducted to investigate the effect of the environmental
      temperature on the immune response of exotic broiler chicks reared in arid-hot
      climate zone (the Sudan). Twenty eight broiler chicks (Lohman) were challenged
      with 1 mL of 10% sheep red blood cells suspension (10% SRBCs) at day 2 and day 13
      during summer (June) and winter (January) seasons. At day 13 and day 20 sera were
      harvested and subjected to hemagglutination test to measure antibody titers
      against 10% SRBCs for primary and secondary immune response, respectively. In
      winter season the antibody titers (GMT) against 10% SRBCs for the secondary
      immune response was so high compared to that in summer season. Nevertheless, the
      antibody titers for primary immune response during winter and summer seasons
      were, somehow, identical although it was a little bit higher during winter
      season. The weights of the lymphoid organs (spleen, thymus and bursa of
      Fabricius) were significantly higher in the winter season compared to summer
      season irrespective of the age.

PMID- 18817215
TI  - Comparison of random amplified polymorphic DNA markers and morphological
      characters in identification of homokaryon isolates of white button mushroom
      (Agaricus bisporus).
AB  - The secondarily homothallic life cycle of the white button mushroom that results
      in scarcity of uninucleate basidiospores (homokaryons) in its progeny, is the
      most important impediment for genetic improvement of the commercial strains.
      Identification of homokaryons for breeding programs of Agaricus bisporus (button
      mushroom) is, therefore, crucial. Verifying homokaryons through fruiting trial is
      time consuming and unreliable. In this study, ability of RAPD markers, compared
      to morphological characters for identification of homokaryon isolates, was
      investigated. Based on morphological characters, 42 isolates were screened and
      exposed to RAPD markers. The results showed that RAPD markers could discriminate
      homokaryons from heterokaryons, based on number of bands generated. The numbers
      of band in homokaryons were significantly less than those of heterokaryons.
      Results also showed that cluster analysis, based on average of band number
      generated, could separate homokaryon from heterokaryon isolates. It is suggested
      that RAPDs could be used to identify hyomokaryons from heterokaryons for breeding
      program of A. bisporus.

PMID- 18817216
TI  - Effects of onion on serum uric acid levels and hepatic xanthine
      dehydrogenase/xanthine oxidase activities in hyperuricemic rats.
AB  - The aim of this study was to investigate the effects of onion on serum uric acid
      levels and hepatic Xanthine Dehydrogenase/Xanthine Oxidase activities in normal
      and hyperuricemic rats. Hyperuricemia was induced by intraperitoneal injection of
      250 mg kg(-1) potassium oxonate in rats. Oral administration of onion at 3.5 and
      7.0 mg kg(-1) day(-1) for 7 days was able to reduce serum uric acid levels in
      hyperuricemic rats with no significant effects on the level of this compound in
      the normal animals. In addition, onion when tested in vivo on rat liver
      homogeneities elicited significant inhibitory actions on the Xanthine
      Dehydrogenase (XDH) and Xanthine Oxidase (XO) activities. This effect resulted
      less potent than that of allopurinol. However, the hypouricemic effect observed
      in the experimental animal did not seem to parallel the change in XDH and XO
      activities, implying that the onion might be acting via other mechanisms apart
      from simple inhibition of enzyme activities. Such hypouricemic action and enzyme
      inhibitory activity of onion makes it a possible alternative for allopurinol, or
      at least in combination therapy to minimize the side-effects of allopurinol, in
      particular in long-term application.

PMID- 18817217
TI  - The role of the procalcitonin in diagnosis of neonatal sepsis and correlation
      between procalcitonin and C-reactive protein in these patients.
AB  - The goal of this study was to investigate the role of procalcitonin (PCT) in
      diagnosis of neonatal sepsis and its correlation with C-Reactive Protein (CRP).
      One hundred and seventeen neonates with the gestational age > or = 35 weeks with
      clinically suspected diagnosis of neonatal sepsis were studied during one year
      from 2007 in Tabriz Children's Hospital. Conventional sepsis workup was done in
      all cases and the diagnosis of neonatal sepsis was proved based on the results of
      blood culture. The serum procalcitonin was measured by quantitative Chemo
      luminance methods and the results were compared with CRP levels between the
      neonates with and without proven sepsis. The results showed among in 117 neonates
      with suspected sepsis 27 (23.1%) cases have positive blood culture (proven
      sepsis). The mean levels of PCT in neonates with and without proven sepsis was
      4.42 +/- 6.66 vs. 2.06 +/- 4.03 ng mL(-1) and CRP 33.98 +/- 36.81 vs. 12.30 +/-
      20.42 mg L(-1) were significantly higher in neonates with proven sepsis (p =
      0.026 and p < 0.001). The sensitivity, specificity, positive predictive value and
      negative predictive value of PCT (more than 2 ng mL(-1)) were 66.7, 50, 28.6,
      83.3 and CRP (more than 3.5 mg L(-1)) were 70.4, 72.2, 43.2 and 89%,
      respectively, in diagnosis of neonatal sepsis. There was a meaningful correlation
      between the level of PCT and CRP in the sepsis group (r = 0.797, p < 0.001). The
      results of the current study showed that more relying on the level of PCT and CRP
      for planning the management of neonates with suspected sepsis is not logical, but
      a negative result may be helpful in ruling it out.

PMID- 18817218
TI  - Incorporation of AMMI stability value and grain yield in a single non-parametric
      index (GSI) in bread wheat.
AB  - In order to determine stable bread wheat genotypes with high grain yield via a
      single parameter, field experiments were conducted with 20 genotypes for 4
      consecutive years in two different conditions (irrigated and rainfed) in a
      completely randomized block design with three replications in each environment.
      Combined analysis of variance showed highly significant differences for the GE
      interaction indicating the possibility of selection for stable entries. The
      results of additive main effect and multiplicative interaction (AMMI) analysis
      revealed 10% of total variability was justified by the GE interaction which was
      2.5 times more than that of genotypes. Ordination techniques displayed high
      differences for the interaction principal components (IPC1, IPC2 and IPC3),
      exhibiting that 83% of the GE sum of squares was justified by AMMI1, AMMI2 and
      AMMI3, i.e., 3.77 times more than that explained by the linear regression model
      displaying the relative efficiency of AMMI1 model in comparison with regression
      model. AMMI stability value (ASV) discriminated genotypes G6, G9, G14, G15, G17
      and G18 as the stable entries. As stability per se is not a desirable selection
      criterion, because the most stable genotypes would not necessarily give the best
      yield performance, hence, simultaneous consideration of grain yield and ASV in a
      single non-parametric index entitled: Genotype Selection Index (GSI),
      discriminated G6 and G17 with general adaptability and high grain yield for
      rainfed and irrigated conditions which was in agreement with the results of
      biplot analysis.

PMID- 18817219
TI  - Effect of vermicompost on growth, yield and nutrition status of tomato
      (Lycopersicum esculentum).
AB  - An experiment was conducted to determine the effects of vermicompost on growth,
      yield and fruit quality of tomato (Lycopersicum esculentum var. Super Beta) in a
      field condition. The experiment was a randomized complete block design with four
      replications. The different rates of vermicompost (0, 5, 10 and 15 t ha(-1)) was
      incorporated into the top 15 cm of soil. During experiment period, fruits were
      harvested twice in a week and total yield were recorded for two months. At the
      end of experiment, growth characteristics such as leaf number, leaf area and
      shoot dry weights were determined. The results revealed that addition of
      vermicompost at rate of 15 t ha(-1) significantly (at p < 0.05) increased growth
      and yield compared to control. Vermicompost with rate of 15 t ha(-1) increased EC
      of fruit juice and percentage of fruit dry matter up to 30 and 24%, respectively.
      The content of K, P, Fe and Zn in the plant tissue increased 55, 73, 32 and 36%
      compared to untreated plots respectively. The result of our experiment showed
      addition of vermicompost had significant (p < 0.05) positive effects on growth,
      yield and elemental content of plant as compared to control.

PMID- 18817220
TI  - Effects of different temperatures on the total carbohydrate, lipid and protein
      amounts of the bean beetle, Acanthoscelides obtectus Say (Coleoptera: Bruchidae).
AB  - This study investigates the effects of different temperatures on the total
      carbohydrate, lipid and protein amounts of Acanthoscelides obtectus Say, which is
      a common cereal pest. Studies have been carried out under laboratory conditions
      at 20 +/- 2 degrees C, 30 +/- 2 degrees C and 60 +/- 5% relative humidity. No
      specific photoperiodic regimen has been used throughout the study. Total
      carbohydrate, protein and lipid amounts for females at 20 degrees C were 61.74,
      35.77 and 83.79 microg/individual, respectively, whereas the amounts for males
      were 34.94, 29.53 and 57.98 microg/individual, respectively. At 30 degrees C,
      total carbohydrate, protein and lipid amounts for females were 92.00, 42.18 and
      83.26 microg/individual, respectively. The amounts at the same temperature for
      males were 43.34, 34.08 and 52.19 microg/individual, respectively. In both sexes,
      total carbohydrate and protein amounts at 30 degrees C were higher than those at
      20 degrees C whereas this was not true for total lipid amounts.

PMID- 18817221
TI  - The study of developmental capacity of vitrified mouse blastocysts in different
      straws after transfer to mouse pseudo pregnant.
AB  - Vitrification is the commonly used method for long-term storage of pre
      implantation mammalian embryos. It is an essential part of assisted reproductive
      technologies. The re-expansion rate, pregnancy and birth rate of vitrified
      blastocysts using CPS were compared with OPS and Conventional Straw. Female NMRI
      mice were injected with Gonadotrophins in order induce them for super ovulation.
      At that time the mice were sacrified by cervical dislocation and dissected of
      mouse abdomen. The uterine horns were existed blastocysts were collected in PBS
      and randomly allocated to four groups: vitrification in CPS, conventional straw,
      OPS and untreated controls. The vitrification solution was EFS40%. After storage
      for 1 month in liquid nitrogen, the blastocysts were thawed in 0.5 M sucrose for
      in vitro culture in M16 medium. After 6 h of culture, the numbers of expanded
      blastocysts was recorded and ready for transfer to uterus of pseudo pregnant
      mouse. The re-expansion rate of the CPS group (72.1%) was significantly higher (p
      < 0.05) than OPS (52.55) and C.S. (38.6%) groups. The pregnancy (70%) and birth
      rate (45%) of blastocysts in CPS were similar to those of fresh blastocysts (80%
      and 45.5%) and the pregnancy (10%) and birth rate (5.1%) in Conventional Straws
      lower than OPS (20 and 7.5%), but were not significantly different. Mouse
      blastocysts vitrified using CPS had a better result compared with OPS and
      Conventional Straw. The value of CPS for vitrification of blastocysts may also
      merit investigation.

PMID- 18817222
TI  - A new algorithm for 2D hydrophobic-polar model: an algorithm based on hydrophobic
      core in square lattice.
AB  - This study was engaged in a new algorithm which was used to solve the problem of
      protein folding. The conformation of hydrophobic core of protein was key factor
      of structure of protein. So, in our algorithm, we set a hydrophobic core which
      was restricted by new aggregate. Then, the hydrophilic residues between two
      hydrophobic residues were ranged, the optimal conformation was gained if all
      residues were not overlap and continuous. The algorithm in this study can be
      prevented effectively falls into partially smallest energy.

PMID- 18817223
TI  - Clinical evaluation of repeated propofol total intravenous anesthesia in dog.
AB  - This current study designed to evaluate any possible changes in required doses
      and other cardiopulmonary findings after repeated propofol total intravenous
      anesthesia (TIVA) in dog. The study was conducted in 6 healthy sheepdogs, weight
      between 16.5 and 28 kg. Anaesthesia induced by 8 mg kg(-1) of propofol and
      maintained by continuous propofol (0.3 mg/kg/min) infusion in saline solution.
      All dogs received three times of propofol anaesthesia with the same protocol in a
      cross over design. As the animals in first, second and third time of anaesthesia
      allocated into groups 1, 2 and 3, respectively. Heart Rate (HR), rectal
      temperature (Temp), blood oxygen saturation (SpO2) by pulse oximetry and non
      invasive arterial blood pressures were measured. Times to the first swallowing
      attempt, ability to lift the head and standing were measured during recovery. The
      apnea was recorded in all animals but no significant difference was recorded
      between groups under study. Calculated doses of induction were sufficient for
      intubation of the animals. The average doses foe maintenance of anesthesia did
      not show any significant difference between groups under study. There were no
      significant differences found between groups in any comparable parameter. Despite
      of longer recovery time in group three, there were no significant differences
      between the Groups in different recovery times. Repeated propofol anesthesia did
      not improve resistance and respiratory changes in this species. However, some
      effects on blood pressure may happen without any effect on heart rate.

PMID- 18817224
TI  - The heterotoxicity of Hordeum vulgare L. extracts in four growth stages on
      germination and seedlings growth of Avena ludoviciana.
AB  - Phytotoxicity of barley extracts (Hordeum vulgare L.) on wild oat (Avena
      ludoviciana Durieu) was investigated. Water extracts five varieties of barley
      were bioassayed on germination and seedling growth of wild-oat to test the
      heterotoxicity of barley on wild-oat, study the dynamics of allelopathic
      potential over four growth stages and identify the most allelopathic plant part
      of barley in each stage. Whole barley plants were extracted at growth stage 4
      (stems not developed enough), whilst for the following growth stages roots,
      stems, panicles and leaves were extracted separately. Seedling growth bioassays
      demonstrated that the wild-oat responded differently to the allelopathic
      potential of barley. For wild-oat radical growth and coleoptile growth were more
      depressed than germination, though. The allelopathic potential of barley plant
      parts was not stable over its life cycle for wild-oat. Leaves and stems were the
      most phytotoxic barley plant parts for wild-oat in the all stages. Among the
      varieties Eizeh appeared as the best one showing toxicity to seed germination of
      wild oat at its stage 4 and 8. Results suggested that the response by wild-oat
      varied depending on the source of allelochemicals (plant part) and the growth
      stage of the barley plant and kind of variety. The results leaded to conclude
      that Eizeh variety of barley was good to grow as it has good check on seed
      germination of wild oat plants as well as it also retarded the growth of root and
      shoot length of oat.

PMID- 18817225
TI  - Impact of aluminum sub-chronic toxicity on body weight and recognition memory of
      wistar rat.
AB  - The aims of this study was to investigate the impact of aluminum nitrate
      administered in drinking water during 90 days (sub-chronic toxicity), on body
      weight gain, motor activity, brain aluminum accumulation and especially in
      recognition memory of wistar rats. Two groups of young female wistar rats were
      used. Treated rats received (80 mg L(-1)) of aluminum nitrate diluted in drinking
      water, while control rats received a drinking water only, for 3 months. An
      evolution of body weight, a motor activity, object recognition memory (NOR) and
      brain aluminum concentration has been evaluated. The body weight was taken
      weekly, whereas the memory abilities and the motor activity are measured once
      every fortnight alternatively, by submitting rats to the open field test and to
      the novel object recognizing memory test. The results have showed a significant
      decrease in rats' body weight (p < 0.05). Though, no significance was registered
      for motor activity. Nevertheless, a high significance is showed for recognition
      memory compared to control rats (p < 0.01), especially at the end of testing
      period, even the difference between control and aluminium treated rats in brain
      aluminum levels was not significant.

PMID- 18817226
TI  - Effect of silymarin on metabolic factors of food-restricted over conditioned
      Wistar rats.
AB  - This study was conducted to evaluate the changes in serum metabolic factors of
      over conditioned pregnant rats treated with silymarin in food restriction
      condition. Sixty pregnant Wistar rats were divided into five equal groups. All
      rats received high energy diet before treatments. Control group were fed ad
      libitum (Non-FR). Rats in other groups received 50% of the food intake of Non-FR
      group and served as food-restricted (FR) groups. Three of five FR groups received
      150, 200 and 400 mg kg(-1) silymarin, respectively (FR-150, 200, 400). Another FR
      group (FR-Con) and the Non-FR group did not receive any silymarin. Glucose,
      triglyceride, LDL and HDL cholesterol, total cholesterol, thyroid hormones and
      cortisol were measured in serum. All factors were significantly different between
      groups except free-T4 and T4. Serum glucose concentrations in FR-150 and 200 and
      Non-FR groups were lower than FR-Con and FR-400. Silymarin significantly
      increased serum triglycerides, LDL cholesterol and cholesterol contents in FR
      groups. The highest levels of these factors were noted in 200 mg silymarin
      treated group. HDL cholesterol was highest in FR-Con; meanwhile FR-200 group had
      the lowest HDL cholesterol. Serum cortisol decreased in treated and untreated FR
      groups except FR-150 group. Free-T3 and T3 concentrations in FR-400 and FR-Con
      groups were higher than the other silymarin treated groups. In conclusion our
      results indicate that 200 mg kg(-1) of silymarin in Wistar rats is the best
      dosage to achieve metabolic benefits. Silymarin has positive effects on lipid
      metabolism and can modulate serum triglyceride and cholesterol concentrations in
      food restriction condition. Also, the present findings suggest that silymarin
      under food restriction situation exerts a decreasing effect upon peripheral
      conversion of T4 to T3.

PMID- 18817227
TI  - Endoscopic findings and Helicobacter pylori in children on long-term
      hemodialysis.
AB  - The aim of this study is to evaluate the prevalence of GI symptoms, endoscopic
      abnormalities, histologic gastritis and Helicobacter pylori infection in children
      with End Stage Renal Disease (ESRD) undergoing maintenance hemodialysis. Upper
      endoscopy and gastric biopsy were performed in 31 consecutive ESRD children from
      2002-2007, before renal transplantation. H. pylori status was determined by
      urease test and histology. The mean age of patients was 11 +/- 3.3 years (4-16
      year). The mean duration of dialysis was 12.4 +/- 11 months (1.5-54 months).
      Seventeen patients (54.8%) were symptomatic. Twenty patients (64.5%) had
      endoscopic abnormalities. Antral erythema, esophagitis, antral nodularity and
      diffuse gastritis were common endoscopic findings. Endoscopic abnormalities were
      more common in symptomatic patients than asymptomatic patients (p < 0.05). Twenty
      patients (64.5%) were H. pylori positive. There was no statistical correlation
      between age, sex, serum creatinine level, presence of any symptoms and endoscopic
      abnormalities with H. pylori positivity. The mean duration of dialysis in H.
      pylori negative patients was significantly longer in comparison with H. pylori
      positive patients. High prevalence of eodoscopic abnormalities and H. pylori
      infection in both symptomatic and asymptomatic patients emphasize the necessity
      of upper GI evaluation in ESRD children before renal transplantation.

PMID- 18817228
TI  - Seroepidemiological study for toxocariasis among children in Zanjan-northwest of
      Iran.
AB  - Determination of seroepidemiological survey of Toxocara infection in 810 sera
      from children inhabitants in rural and urban area of Zanjan (North-West of Iran)
      was adjusted for specific antibody level against of second stage larvae of
      Toxocara for excretory and secretory antigens based on ELISA technique. In
      contrast of the other studies, the overall seroprevalence was quite low, reaching
      to 2.7% out of 810 samples was positive to anti Toxocara species antibodies.
      Neither age nor gender seemed to be significant factor to positive serology.
      Seroprevalence of anti Toxocara antibody were detected in 8 out of 494 (1.6%)
      children from urban area, whereas 316 sample (4.4%) were the positive in the
      rural area. Positive children who had contact or ownership of cats and dog were
      6.9 and 3.9%, respectively. Albeit, concerning to this study, seroprevalence of
      toxocariosis is lower than other countries and other studies in Iran. But
      protections of toxocariosis in children must be taking into account in public
      health program. Suggest that increase of hygiene education would be a crucial
      affective on population to reduce infection risk factor and zoonotic disease.

PMID- 18817229
TI  - Effect of dietary garlic on immune response of broiler chicks to live Newcastle
      Disease vaccine.
AB  - This study was designed to determine the effect of garlic powder on humoral
      immune response of broilers against NDV (Newcastle Disease Virus) vaccine. Two
      hundred and forty, two-day-old, Ross chicks were randomly assigned into 4 groups
      of 60 birds each. Chicks in groups 1 and 2 were given control mash diet during
      the experiment (6 week), but those in groups 3 and 4 were fed on control diet
      supplemented with 1 and 3% garlic powder, respectively. All groups except number
      1 were vaccinated by eye-drop with B1 strain (Pestikal, Croatia) at 9 and 18 days
      of age. Ten blood samples were taken from each group on days 0, 14, 24 and 34
      after first vaccination. The serum antibody level against NDV was measured by
      both HI and ELISA tests. The EDTA-mixed blood samples were examined for total and
      differential leukocyte count. The results showed that antibody titers in
      vaccinated chicks were significantly more than in non-vaccinated chicks (p <
      0.05), but not influenced by the diet (p > 0.05). A significant increase of total
      leukocyte and percentage of lymphocytes was observed in vaccinated chicks 14 days
      after vaccination, but there were no difference (p > 0.05) among vaccinated
      groups. It is concluded that inclusion of garlic powder to the diet of broilers
      don't have any beneficial effect on humoral immune response to live NDV vaccine.

PMID- 18817230
TI  - Amyloid deposits in senile vertebral arteries, immunohistological and
      ultrastructural findings.
AB  - In a study on amyloid deposits in vertebral arteries, many elderly patients
      showed amyloid deposits in the perivascular tissue. These proved to be senile
      systemic amyloidosis of the transthyretin-type by immunohistochemistry. Amyloid
      deposits were also found in the arterial wall. These intramural amyloid deposits
      showed significant affinity to elastic material of the arterial wall. The
      intramural amyloid deposits did not react with any of the known or available
      antibodies to amyloid subtypes. Only a polyclonal antibody to human elastin could
      mark this type of amyloid. It may therefore be assumed that the precursor protein
      of this amyloid is derived from elastin molecules. By electron microscopy, the
      light microscopic amyloid deposits were of fibrillary structure, typical for
      amyloid with a direct contact to elastic material.

PMID- 18817231
TI  - The effect of Rhizobium spp. inoculation on seed quality of bean in Turkey.
AB  - Rhizobium spp. (local isolate) was used to inoculate three bean (Phaseolus
      vulgaris L.) varieties; Akman 98, Goynuk 98 and Sehirali 90, in a factorial field
      experiment. The objective of the experiment was to study effect of inoculation on
      seed yield, protein range, seed weight, non-soaker capacity and hydration index.
      Rhizobium spp. inoculation and nitrogen fertilizer significantly increased
      characters tested. This study revealed that inoculation with Rhizobium spp.
      improved seed quality.

PMID- 18817232
TI  - Survey of outcome of asthmatic children referred to outpatient clinic of Tabriz
      University of Medical Sciences.
AB  - This study was designed to follow patients regarding to achieving control,
      identify disease exacerbations and discover relation between exacerbation and
      risk factors. In a cross sectional-analytic study, 400 asthmatic patients in the
      range of 2-14 years old who were visited at the specialized outpatient clinic of
      Tabriz University of Medical Sciences were divided and studied on the base of
      disease severity. At the end (at least one year treatment), patients were
      categorized based on level of disease control and one year after this stage,
      cases of exacerbation were identified and studied. By excluding patients with
      poor adherence, 342 patients continued treatment as intermittent, mild
      persistent, moderate persistent and severe persistent asthma (38, 235, 61 and 8
      patients, respectively). After a period of one year treatment, the patients were
      divided as well controlled, partly controlled and uncontrolled (68, 30 and 2%,
      respectively). Cases of disease exacerbations were more if sinusitis, familial
      asthma history and poor adherence were present (p < 0.01, p < 0.001 and p < 0.05,
      respectively). There is meaningful association between poor adherence, sinusitis
      and positive family history of asthma with disease exacerbation.

PMID- 18817233
TI  - Morphology and morphometrics of Heterodera filipjevi (Madzhidov, 1981) Steller,
      1984 from Kohgiluyeh and Boyer-Ahmad province, Iran.
AB  - During 2007 and 2008, soil samples of wheat and barley fields of the cold regions
      of the Kohgiluyeh and Boyer-Ahmad province were surveyed for cereal cyst
      nematode. In 65% of samples cysts were seen. Morphological and morphometrics of
      cysts, cone top structure and second stage juveniles of the isolated populations
      were studied. Detailed taxonomic studies revealed the existence of H. filipjevi.
      This is the first report of the species in the province.

PMID- 18817234
TI  - Preemptive analgesia with local lidocaine infiltration for single-level open disc
      operation.
AB  - To evaluate the impact of preemptive local analgesia at the incision site for
      postoperative pain in patients undergoing disc operation. In this prospective,
      randomized, double-blinded, placebo-controlled study 166 patients were assigned
      to either lidocaine (n = 83) or placebo (n = 83) groups. The incision site was
      infiltrated with either 20 mL of 2% lidocaine and 0.9% saline in lidocaine group
      or 0.9% saline before the incision. Morphine (5 mg) was used for postoperative
      pain treatment. Postoperative pain was measured with Visual Analog Scale (VAS) in
      6, 12, 24 and 48 h. Data were analyzed with SPSS software, using Chi-square and t
      tests. The groups were matched for age, sex, type of operation, mean length of
      hospital stay and mean length of operation. Statistical analysis revealed no
      significant difference in visual analog scores of pain severity at 6, 12, 24 and
      48 h after surgery between lidocaine and placebo groups (6 h: 38.22 +/- 26.87 vs.
      34.52 +/- 24.43, p = 0.35; 12 h: 33.26 +/- 28.83 vs. 28.01 +/- 24.71, p = 0.20;
      24 h: 26.71 +/- 23.31 vs. 22.85 +/- 22.48, p = 0.27; 48 h 16.35 +/- 10.16 vs.
      15.23 +/- 8.90 p = 0.45). The amount of narcotics used post operatively had no
      meaningful difference in the groups (lidocaine 10.07 +/- 8.24 mg vs. placebo
      10.54 +/- 9.31 mg p = 0.73). Preemptive analgesia with lidocaine 2% used
      subcutaneously before skin incision has no effect in reducing postoperative pain,
      narcotics demand and duration of hospital stay.

PMID- 18817235
TI  - The study on foliar micromorphology of Hippobromus pauciflorus using scanning
      electron microscope.
AB  - Foliar micromorphology of Hippobromus pauciflorus (L.f.) Radlk (Sapindaceae) was
      investigated by scanning electron microscope examination. The leaves were
      characterized by anisocytic stomata which were found only on the abaxial surface.
      The leaves have long unicellular non-glandular trichomes which were distributed
      over the mid rib and densely populated at the edges of the upper and lower
      surfaces. Crystal deposits were also observed on the abaxial surface of the
      leaves. Energy dispersive X-ray spectroscopy SEM of the crystals showed
      predominant mineral components of Na, Al, Si, K and Ca ions. These micro (Si, Na
      and Al) and macro (K and Ca) elements are very essential to plant growth. Their
      presence in the trichomes could contribute to the mechanical stability of the
      leaf appendages.

PMID- 18817236
TI  - Effect of educational plan on adherence rate among children with persistent
      asthma.
AB  - This study was conducted to survey the effect of education and regular follow up
      on adherence rate of children with mild to moderate persistent asthma. In a semi
      experimental study (before and after), two groups of children with mild to
      moderate persistent asthma, referred to outpatient clinic of Tabriz University of
      Medical Sciences were compared. First group included 200 asthmatic children who
      were treated at least for duration of one year by conventional method. The second
      group included 300 patients at the same age and severity of disease that were
      treated at least one year by a comprehensive plan of education and regular follow
      up visits as well. Data were analyzed by Chi-square and p < 0.05 was considered
      as significant difference. Findings indicate that in first group 100 (50%) and
      second group 295 (84/3%) had adherence rate more than 50% (p = 0.00). Considering
      adherence rate of > or = 50% there was significant difference between two groups
      with mild persistent asthma (p = 0.00). Present findings indicate that education
      and scheduled follow up can result in higher degree of adherence.

PMID- 18817237
TI  - Effects of gabapentin on early postoperative pain, nausea and vomiting in
      laparoscopic surgery for assisted reproductive technologies.
AB  - Prevention and treatment of postoperative pain, nausea and vomiting continues to
      be a major challenge in postoperative care. This study was designed to compare
      the effects of small dose of oral gabapentin with placebo as premedication on
      early postoperative pain, nausea and vomiting in patients undergoing ambulatory
      laparoscopic surgery for Assisted Reproductive Technologies (ART). Seventy women
      undergoing ambulatory laparoscopic surgery were randomly assigned to receive oral
      gabapentin 300 mg or placebo as premedication 1 h before surgery. Patients were
      anesthetized with the same anesthetic techniques. Duration of anesthesia,
      severity of postoperative pain and presence of Post Operative Nausea and Vomiting
      (PONV) were compared between the study groups. Demographic data and the duration
      of anesthesia were not statistically different between the study groups. There
      were significant differences in median VAS scores (25th-75th) measurements at all
      time points in the study groups (p < 0.05). Ten patients (28%) in control and one
      patient (0.02%) in gabapentin group required additional IV analgesic that was
      statistically significant (p = 0.012). Two patients in gabapentin and nine
      patients in placebo group had nausea (p = 0.022). None of patients in gabapentin
      but four patients in placebo group had vomiting (p = 0.114). Administration of
      oral gabapentin 300 mg before ambulatory laparoscopic surgeries, decreased
      postoperative pain, analgesic requirement and nausea.

PMID- 18817238
TI  - Diagnosis of airway malacia by virtual bronchoscopy.
AB  - The study was aimed to identify the role of virtual bronchoscopy in detection of
      airway malacia in children. In a pre-experimental study over 3 years (from Nov.
      2003 to Oct. 2006), 35 consecutive patients were presented to Tabriz Children's
      Hospital with clinical manifestations of airway malacia, examined by the
      technique of virtual bronchoscopy. Thirty five patients including 23 males and 12
      females with the mean age of 3.7 +/- 1.6 months were studied. The presence of
      airway malacia and its location and severity were determined by virtual
      bronchoscopy in all studied cases; that revealed: laryngomalacia, bronchomalacia,
      tracheomalacia, laryngotracheomalacia and laryngobronchomalacia in 42.8, 25.7,
      20, 8.6 and 2.9% of patients, respectively. Virtual bronchoscopy is a non
      invasive, accurate and rapid imaging technique with an excellent validity for
      diagnosis of airway malacia and stenosis, therefore it can replace conventional
      bronchoscopy.

PMID- 18817239
TI  - Histological and haematological disturbance caused by arsenic toxicity in mice
      model.
AB  - Histological and hematological disturbance caused by Arsenic containing water
      were studied in mice model. Animal were divided into four groups. Control group
      exposed to arsenic free distilled water and 3 treatmental group exposed to the
      arsenic containing water with 30, 150 and 300 ppb. Blood samples and organs were
      collected after 40 days. Histopathological results revealed mild to severe type
      of necrosis and degenerative changes in kidney and liver of arsenic feed animals.
      Kidney of the 300 ppb group showed severe type of necrosis and degenerative
      changes in distal and proximal tubules. The renocytes of proximal and distal
      tubules were showing hydropic and fatty degeneration. Due to degenerative changes
      cells were showing cytoplasmic vacoulation and cytoplasmic and nuclear blebbing.
      Glomeruli cells were contracted and increased the bowman's spaces. Varied degrees
      of changes were also observed in 30 and 150 ppb exposed group. Necrosis of
      hepatocytes and cytoplasmic blebbing were also observed. The sinusoidal spaces
      were expanded due to shrinkage and necrosis of hepatocytes. Spleenocytosis
      occurred in spleen and the parenchymal and mesenchymal cells were replaced by
      connective tissue. The lymphocytes were severely damaged by arsenic toxicity.
      White Blood Cells (WBCs), Red Blood Cells (RBCs) and hemoglobin level in control
      groups were in normal range where as level were significantly decreased with the
      increase dose of arsenic in the respective treatmental groups. The data was
      analyzed statistically and was found that significant was found among the group
      (p<0.05).

PMID- 18817240
TI  - Light and electron microscopic study on a haemogregarine species infecting the
      viper cerastes Cerastes gasperitti from Saudi Arabia.
AB  - A Haemogregarine sp. infecting the Viper Cerastes cerastes gasperitti (35%) from
      K.S.A. was recorded for the 1st time. Parasites were recorded exclusively in the
      red blood cells of the Vipers. Erythrocytic parasites measured 17.5 x 3 microm
      with a nucleus of 8.1 x 2.5 microm. Mature Schizonts of 30 x 2.5 microm and
      producing 18-30 merozoites by ectomerogony were reported in the endothelial cells
      of blood capillaries of different internal organs (liver, spleen and lung). The
      merozoites measured 13 x 3.5 microm and these were similar to the stages in the
      red blood cells. The motile stages of the parasite recorded in the present study
      showed all the general architectures of the Apicomplexa with some pecularities
      such as presence of micronemes and rhoptries at both sides of the nucleus and the
      occurance of large number of subpellicular microtubules (80-90) extending to the
      posterior end of the parasite.

PMID- 18817241
TI  - Physical soil properties and slope treatments effects on hydraulic excavator
      productivity for forest road construction.
AB  - Effects of moisture, porosity and soil bulk density properties, grubbing time and
      terrain side slopes on pc 220 komatsu hydraulic excavator productivity were
      investigated in Miana forests road construction project which located in the
      northern forest of Iran. Soil moisture and porosity determined by samples were
      taken from undisturbed soil. The elements of daily works were measured with a
      digital stop watch and video camera in 14 observations (days). The road length
      and cross section profiles after each 20 m were selected to estimate earthworks
      volume. Results showed that the mean production rates for the pc 220 komatsu
      excavators were 60.13 m3 h(-1) and earthwork 14.76 m h(-1) when the mean depth of
      excavation or cutting was 4.27 m3 m(-1), respectively. There was no significant
      effects (p = 0.5288) from the slope classes' treatments on productivity, whereas
      grubbing time, soil moisture, bulk density and porosity had significantly
      affected on excavator earthworks volume (p < 0.0001). Clear difference was showed
      between the earthwork length by slope classes (p = 0.0060). Grubbing time (p =
      0.2180), soil moisture (p = 0.1622), bulk density (p = 0.2490) and porosity (p =
      0.2159) had no significant effect on the excavator earthworks length.

PMID- 18817242
TI  - Polyphenol contents and antioxidant activities of five Indigofera species
      (Fabaceae) from Burkina Faso.
AB  - Aqueous acetone extracts prepared from five Indigofera species of Burkina Faso,
      namely Indigofera colutea (Burm.) Murril., I. macrocalyx Guilld et Perr., I.
      nigritana Hook f., I. pulchra willd. and I. tinctoria L., were investigated for
      their phytochemical composition and their antioxidant activities. Standard
      methods and TLC were used to screen the phytochemical composition. The total
      phenolic and flavonoid content of extracts were assessed by Folin-Ciocalteu and
      AlCl3 methods, respectively. These extracts were also evaluated for their
      antioxidant potentials using ferric reducing antioxidant power (FRAP), 2,2
      diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azinobis(3-ethylbenzothiazoline-6
      sulphonate) (ABTS) assays. Flavonoids, saponins, quinones, sterols/triterpenes
      and tannins were present in all these species except for I. pulchra where
      quinones were not found. Gallic acid, caffeic acid, rutin and myricetin in I.
      colutea; gallic acid, quercitrin, myricetin in I. tinctoria; galangin and
      myricetin in I. macrocalyx were identified by thin layer chromatography. Among
      these, I. colutea, I. tinctoria, I. nigritana and I. macrocalyx, which had the
      highest phenolic content, were also found to possess the best antioxidant
      activities. The results indicated a good correlation between antioxidant
      activities and total phenolic content (p<0.05 for FRAP/DPPH and DPPH/ABTS and
      p<0.01 for FRAP/ABTS). These plants represent promising sources of natural
      antioxidants and these findings give scientific bases to their
      ethnopharmacological uses.

PMID- 18817243
TI  - Separation of DNA for molecular markers analysis from leaves of the Vitis
      vinifera.
AB  - In the present study, three DNA extraction procedures were examined to determine
      which might yield DNA from Grape leaves suitable for molecular analysis for RAPD,
      SSR. AFLP and etc analysis. The three methods examined were: the miniprep
      procedure and the modified CTAB for difficult species and protocol CTAB. Only the
      modified CTAB method consistently yielded DNA suitable for Polymerase Chain
      Reaction (PCR) amplification, regardless of plant growing conditions or leaf age.
      The quality and quantity of extracted genomic DNA gained from these methods are
      deliberated by means UV biophotometer, electrophoresis in 1.2% agarose gel and
      PCR. In this regard, application chosen for young and mature leaves, the most
      value of qualified DNA, is extracted from fully expanded leave when PVP was added
      to the extraction buffer. This same procedure also yielded PCR-amplifiable DNA
      from various other perennial, woody species and from other fruit species such as
      apple (Malus domestica), cherry (Prunus avium), peach (Prunuspersica), plum
      (Prunus domestica). DNA yield from this procedure is high (up to 1 mg g(-1) of
      leaf tissue). DNA is completely digestible with restriction endonucleases and
      amplifiable in the Polymerase Chain Reaction (PCR).

PMID- 18817244
TI  - Assessment of chronic gastritis in pet dogs and its relation with helicobacter
      like organisms.
AB  - The aim of this study was to evaluate the prevalence of chronic gastritis in pet
      dogs, to determine the histopathologic changes of gastric mucosa and, to
      determine its relationship with canine gastric Helicobacter infection. Sixty
      percent (n = 18), 27% (n = 8) and 13% (n = 4) of the examined stomachs showed
      normal, congested and erosive gastric mucosa respectively. Histopathologic
      examination was confirmed the presence of chronic gastritis in 40% of dogs (n =
      12). Lymphocytic-plasmacytic gastritis was the most common type of chronic
      gastritis. Gastric Helicobacter was detected in cytological examination of 26 out
      of 30 dogs (86.6%) but in the PCR analysis, 93% of gastric samples were positive
      for GHLO. There was no significant relation between the presence of Helicobacters
      and chronic gastritis (p>0.05). Follicular gastritis was detected in 12 cases
      (40%) and there was also no significant correlation between its presence and
      GHLO's infection (p>0.05). In conclusion, chronic gastritis can be considered as
      a prevalent disease especially in dogs. Nutritional and environmental factors as
      well as individual immune response may have role in induction of chronic
      gastritis, but the clinical significance of these histopathologic changes should
      be evaluated.

PMID- 18817245
TI  - Growth optimization and organogenesis of Gerbera jamesonii Bolus ex. Hook f. in
      vitro.
AB  - Regeneration potentials in Gerbera jamesonii Bolus ex. Hook f. from tissues
      culture system was studied using leaf, petiole and root explants. In vitro
      regeneration, callus induction and root formation were optimized by manipulation
      of growth regulators during organogenesis. Various kinds of plant growth
      regulators such as 6-Benzylaminopurine (BAP), alpha-Naphthalene acetic acid
      (NAA), 2, 4-Dichlorophenoxyacetic acid (2,4-D), Indole-3-acetic acid (IAA),
      Indole-3-Butyric acid (IBA), N6-[2-Isopentenyl]adenine (2iP), Kinetin and Zeatin
      were used to initiate cultures. These plant growth regulators were added to
      Murashige and Skoog medium in different combinations and concentrations.
      Adventitious shoots were obtained from petiole explants cultured on Murashige and
      Skoog (MS) medium supplemented with 2.0 mg L(-1) BAP and 0.5 mg L(-1) NAA.
      Effectiveness of shoot regeneration medium, type of growth regulator used and
      duration of induction period were investigated. Leaf explants cultured on MS
      medium supplemented with 1.0 mg L(-1) BAP and 2.0 mg L(-1) 2, 4-D showed the best
      results for callus induction. Root explants were found to be non-regenerative in
      all experiments conducted. Petiole segment was identified as the best explant for
      regeneration of this species. Regenerated plants were rooted on Murashige and
      Skoog basal medium. Plantlets were then transferred to field with 75% survival
      rate.

PMID- 18817246
TI  - The seeds quality of Betula pndula Roth and Betula oscura Kotula from semi
      natural and anthropogenic habitats.
AB  - This research presents the results of the study of seeds quality of two Polish
      native species of the genus Betula L. (Betula pendula Roth and Betula obscura
      Kotula), growing on the semi-natural (low human activities) and anthropogenic
      (high human activities) habitats. In this study the generative phase has been
      investigated to find differences between studied taxa and try to find out why
      population of B. obscura is very rare. In this research we have checked the
      quality of the seeds from B. obscura and B. pendula and test the survival of
      seedlings sowed into the ground researched in laboratory conditions. Results of
      germination capacity shown significant difference between trees from the
      anthropogenic and semi-natural sites; the energy capacity indicated significant
      difference between trees: B. pendula and B. obscura from all study areas. Mixed
      model ANOVA/MANOVA for seedlings growth showed statistically important effects of
      factors (species, area, months). The results show that B. obscura grows better on
      the anthropogenic habitats than B. pendula, but the latter had more of the fully
      developed seeds and higher germination and seeds energy capacity.

PMID- 18817247
TI  - Determination of the best level of dietary energy with two diet formulation
      methods based on total and digestible amino acid on broiler diet.
AB  - In order to evaluate the effects of different levels of energy and methods of
      formulation of Amino Acid (AA) requirements of diets, this experiment was
      conducted using 392 broiler chicks. The experiment was carried out using a
      complete randomize block design with 7 levels of energy 3175, 3075, 2975, 2875,
      2775, 2675 and 2575 kcal kg(-1) for grower diet and 3225, 3125, 3025, 2925, 2825,
      2725 and 2625 kcal kg(-1) for finisher diet and two methods of formulation of
      diets AA requirements (total and digestible) as a factorial arrangement. Results
      showed that by increasing level of energy feed intake, body weight and FCR were
      promoted in grower diet (p<0.05). Effect of decreasing level of energy up to 2725
      and 2825 kcal kg(-1) was not significant on body weight and FCR in finisher diet,
      respectively. Formulating of diet based on total or digestible AA affected feed
      intake and FCR in finisher diet (p<0.05). Interaction effect of independent
      factors affected on body weight in grower diet (p<0.05). Decreasing level of
      energy increased gastrointestinal tract percentage weight (p<0.05). Formulation
      of diet based on digestible AA decreased gastrointestinal tract percentage weight
      (p<0.05). Abdominal fat decreased significantly as ME content of diets decreased.
      Results showed that it's possible to reduce the level of energy up to 3175 kcal
      kg(-1) in grower and 2725 kcal kg(-1) in finisher diet for giving the best and
      economical performance response. Formulation of diet based on digestible AA in
      finisher diet resulted in promotion of performance.

PMID- 18817248
TI  - Hypocholesterolemic effects of dietary soybean vs. casein proteins in a crossed
      over diets in rat.
AB  - To investigate the effects of dietary proteins on the level of serum total
      cholesterol (TC), triglyceride (TG) and high density lipoprotein (HDL), 32 male
      Wistar rats were randomly divided in control and 3 experimental groups (El, E2
      and E3). The feeding regimes of rats were as follow: control, standard diet; E1,
      a cholesterol free diet containing 20% soybean protein; E2, a cholesterol free
      diet containing 20% casein and E3, a cholesterol free diet containing 10% soybean
      protein and 10% casein. The experimental period was 11 weeks but at the end of
      7th week the diets of E1 and E2 groups were crossed over for the next 4 weeks.
      Blood samples were collected weekly, via the ophthalmic sinus and the serum
      levels TC, TG and HDL were measured. In comparison with control group, the
      results show that at the end of 7th week TC levels in E1 and E2 groups were
      significantly (p<0.05) increased while HDL level unchanged and the TC value of E2
      was bigger (not significant) than E1. However by crossing over the diets, the TC
      level was significantly (p<0.05) diminished in E2 while TG value remarkably
      (p<0.05) increased. These results indicate that soybean protein may insert its
      hypocholesterolemic effect in hypercholestrolemic condition than in
      normolipidemic condition.

PMID- 18817249
TI  - The effect of the air blast sprayer speed on the chemical distribution in
      vineyard.
AB  - A study was conducted to determine the spray deposition patterns for air blast
      sprayers used to apply chemicals to the canopy of Semillon grapevine in vineyard.
      The application carried out in 12 bars and three sprayer speed (2.1-4.9-7.7 km h(
      1)). The spray deposition was measured on the point in the different distances
      (1.5-3-6-9 m). Tartrazine were applied as tracer material. Maximum spray deposit
      was obtained 66.1 mg cm(-2) at sprayer speed of 2.1 km h(-1) and minimum deposit
      was obtained 37.1 mg cm(-2) at sprayer speed of 7.7 km h(-1). The results showed
      that the sprayer speeds had significant effect on spray deposit distribution and
      increasing of the sprayer speed increased drift.

PMID- 18817250
TI  - An abattoir study on hepatic tumors of sheep.
AB  - The aim of the present study was to assess the incidence and age distribution of
      hepatic tumors of sheep as well as study of their histopathologic
      characteristics. For this purpose, 3000 slaughtered sheep, consisting of 284 rams
      with approximate age of 7 to 20 months and 2716 ewes with approximate age of 3 to
      7 years, were inspected during a routine postmortem examination. This study was
      conducted at Tabriz abattoir in the East Azerbaijan province of Iran, in a course
      of 8 months from March to November 2006. In this survey, two livers were
      encountered tumoral. Representative sections of the tumors were stained with
      hematoxylin and eosin. Gross and microscopic features of these tumors supported
      diagnosis of hepatocellular carcinoma and cholangiocellular carcinoma for a seven
      years-old crossbreed ewe and a five-years-old native breed ewe respectively. In
      this survey, 0.074% of slaughtered ewes had hepatic neoplasia. That is, the
      prevalence of hepatocellular carcinoma and cholangiocellular carcinoma in aged
      ewes was equally 0.037% in this study.

PMID- 18817251
TI  - Rapid detection of Potato Y potyvirus in potato farms of Kermanshah using RT-PCR
      amplification of the P1-protease gene and its cloning.
AB  - In this study, the RT-PCR method was used to detect the Y virus in potato tubers
      and leaves. Samples suspicious of virus infection with symptoms of virus
      infection were gathered from farms in Kermanshah and placed in plastic bags and
      kept at -80 degrees C temperature in order to maintain the RNA of the virus until
      extraction. The extraction and purification of RNA were carried out using Tri
      Reagent kit. One of the virus genes is the P1 protease gene which codes a
      proteinase enzyme. This enzyme plays a role in breaking the initial polyprotein.
      For amplification of this gene three primer, including primer-1, primer-2 and
      primer-3, were designed and used. Using primer 1 and reverse transcriptase
      enzyme, cDNA was synthesized and then PCR was performed using the primers 1, 2
      and 3. The PCR products were examined by agarose gel electrophoresis (1%).
      Consequently, two pieces of DNA (400 and 800 bp) were yielded which were
      identical to the genome DNA sequencing. Thus, the proposed technique is a
      convenient method for quick and accurate detection of viruses and, therefore, the
      application of this method for detecting Potato Y virus in potato farms is
      recommended.

PMID- 18817252
TI  - Isolation and identification of Ornithobacterium rhinotracheale in broiler
      breeder flocks of Guilan province, north of Iran.
AB  - The aims of the present study were to isolate and serotype, determine the
      Seroprevalence, Drug susceptibility and diagnosis of infection by Polymerase
      Chain Reaction (PCR). In this study 460 serum samples and 220 tracheal swabs, 90
      ovaries and oviduct swabs, 90 misshapen egg shells swabs were collected from 22
      broiler breeder flocks of 5 companies. Serological results showed that all of the
      22 flocks (100%) were positive for ORT infection. Ornithobacterium rhinotracheale
      (ORT) antibodies were detected in 289 (62/83%) out of the 460 serum samples. ORT
      was detected from tracheal swabs of seven flocks (31/81% or 3/18% out of 220
      tracheal swabs). There was significant correlation between flock different ages
      and ORT titers (p<0.05), but correlation of flock ages and ORT isolates was not
      significantly different (p>0.05). Seven flocks infected with ORT were detected
      positive in PCR but bacteria were Isolated from only five culture. No ovaries and
      oviducts, misshapen egg shell swabs yielded ORT. A 784 bp fragment of the 16S
      rRNA gene was amplified using ORT specific primers in the PCR. All the isolates
      were identified as serotype A by Rapid Agglutination Test. Drug sensitivity test
      using standard disk diffusion technique was performed with 27 antibiotics.
      Antibiotic susceptibility for Quinolons family was seen more than the others and
      Cephalosporins family except to Cephalexin. The isolates were 80-100% susceptible
      to Tetracycline family and the most antibiotic resistant were seen for
      Aminopenicillins, Polypeptides, Sulfanamides and 80-100% resistant to
      Aminoglycoside family. Eighty percent of the isolates were resistant to Licomycin
      and 60% were moderate sensitive to Lincomycin. This study is the first report of
      prevalence of ORT, bacterial isolation, biochemical characteristics, serotyping
      and molecular method (PCR) in broiler breeder flocks in Guilan province of Iran.

PMID- 18817253
TI  - Antispasmodic effect of Piper nigrum fruit hot water extract on rat ileum.
AB  - The aim of this study was to investigate the effect of black pepper fruit hot
      water extract (BPE) on rat ileum contractility and the mechanism(s) of its
      action. The extract was prepared by adding black pepper powder to boiling
      distilled water followed by evaporated the solvent. Ileum was dissected from male
      adult rat (Wistar) and in Tyrode solution the tissue contractions were recorded
      by an isotonic transducer under 1 g tension. The cumulative concentrations of the
      BPE (0.0625-1 mg mL(-1)) reduced the ileum contractions induced by KCl (60 mM) or
      carbachol (10 microM) concentration dependently (p<0.001). In Ca2+-free Tyrode
      solution with high potassium (60 mM), BPE, (0.0625-1 mg mL(-1)) attenuated the
      contractions induced by cumulative concentrations of CaCl2 (0.225-2.7 mM)
      concentration dependently (ANOVA, p<0.05). The incubation of the tissue
      preparation (20 or 30 min) with L-NAME (100 microM), naloxone (1 microM) or
      propranolol (1 microM) did not reduce the extract antispasmodic effect on KCl
      induced ileum contraction. The extract spasmolytic effect was attenuated neither
      by glibenclamide (10 microM) nor by tetraethylammonium (1 mM). Present results
      suggest that the spasmolytic effect of the extract on rat ileum was possibly
      mediated via Ca2+ influx.

PMID- 18817254
TI  - Rapid detection of Salmonella dublin by PCR amplification of the SopE gene and
      its cloning.
AB  - This study is directed towards the method of amplifying and cloning the SopE
      gene, that encodes Salmonella outer protein E. Strains used in this study were S.
      dublin collected from Kermanshah province. Genomic DNA was extracted by the
      general boiling method. Using the specific primers, a part of SopE gene was
      multiplied. The PCR product was inserted into the cloning vector (pTZ57R/T).
      Furthermore, E. coli DH5alpha bacteria were transformed to amplify the
      recombinant plasmid. Recombinant clones were identified by blue/white selection.
      Recombinant plasmids were purified by alkaline lysis procedure. Moreover,
      identity of the SopE/pTZ57R/T product was confirmed by restriction enzyme
      digestion assay and sequencing. Finally, the cloned gene was compared with that
      published by the NCBI Genbank (L78932). The results showed that the obtained
      sequence differed in four nucleotides which resulted in two amino acid
      differences. The cloned SopE was submitted to the NCBI Genbank (EU399750).

PMID- 18817255
TI  - Determination of the best temperature and dry condition in carrot primed-seeds.
AB  - Seed priming and drying condition effects were investigated immediately after
      seed-priming and 9 week after the storage. In this experiment, carrot seeds of
      'Forto C.V.' were used. These seeds were individually primed for 10 days at 20
      degrees C and in PEG (6000) (273 g L(-1)) and KNO3 (200 mmol) solutions. Then
      they were dried for 1 and 2 h at 15, 25 and 30 degrees C, respectively. One part
      of the seeds was stored at 5 degrees C in RH/45% For 9 week. Chemical priming
      effects, drying temperature as well as germination temperature on different
      traits especially germination percentage were significant. However, drying time
      had no significant effect on germination percentage after storage period. PEG
      priming and drying at 25 degrees C for 2 h provided the best condition for
      germination percentage. Using the best material for pre-priming, along with
      suitable drying management with appropriate quality and good conditions of the
      storage is important.

PMID- 18817256
TI  - Evaluation of different media and methods of cultivation on the production and
      viability of entomopathogenic fungi, Verticillium lecanii (Zimm.) Viegas.
AB  - For mass production of V. lecanii, three types of cultivation methods including
      liquid, solid and diphasic production systems were investigated. In the liquid
      state of production, six media were tested in stationary culture conditions.
      Among the six media tested, Molasses Yeast Broth (MYB) supported maximum
      sporulation (8.33 x 10(8) spores mL(-1)) and biomass production (746 mg/100 mL).
      In the MYB, 4% molasses concentration was found to produce highest spore count
      (8.56 x 10(8) spores mL(-1)) and biomass (776 mg/100 mL) followed by 5 and 6%
      molasses. Among the six solid substrates tested, rice grains supported highest
      spore production (1.14 g/100 g). In diphasic state of production, combination of
      MYB and rice grains produced the greatest amount of spores, (1.70 g/100 g).
      Results of this study indicated that diphasic method using MYB as liquid medium
      and rice as solid substrate are the best method and media for mass production of
      V1-7 isolate of V. lecanii.

PMID- 18817257
TI  - Is the cardiorespiratory fitness affected by height of young girls?
AB  - The purpose of the present study was to examine the effect of height in the
      predicted VO2max by the Queens Step test among short and tall young girls. A
      sample of 38 individuals was selected in two stages from a total of 500
      individuals and was assigned to two groups of short (n = 20) and tall (n = 18).
      In order to examine the effect of height in the predicted VO2max, the Queens step
      protocol and the incremental treadmill speed test were used. Respiratory exchange
      was measured continuously throughout the test by an automated open-circuit gas
      analysis system. The study results showed that tall girls revealed a higher
      VO2max on the Queen's step and treadmill tests than short girls (Queen's: 44.09+/
      2.66 vs. 38.96+/-1.65; Treadmill: 34.03+/-7.26 vs. 28.15+/-5.09 mL/kg/min). Based
      on the obtained findings it can be concluded that the higher VO2max seen in tall
      girls on the both protocols, may be due to their physiological and physical
      properties; therefore, it seems that designing of the adjustable steps to the
      height of subjects for optimizing the estimation of VO2max is not necessary and
      other physiological factors may be involved, which require further investigation.

PMID- 18817258
TI  - Continuation rates and reasons for discontinuing TCu380A IUD use in Sari, Iran.
AB  - This study reports results from a 60-month study on the use of TCu380A IUD among
      400 women in Sari, Iran. The aim of this study was to assess a sample of women in
      our region who requested removal of their IUD, continuation rates use and reason
      for discontinuation. This is a cohort study on 400 women who using the TCu380A
      IUD and referred to medical health centers of Sari/Iran from May 1999 to May
      2006. We randomly selected one half of all health and medical centers in Sari (a
      total of 20 centers). At each selected center, we randomly sampled 10% of all IUD
      subjects whose insertion occurred between May 1999 and May 2006. Obtained data
      were analyzed by descriptive statistical methods. Continuation rates at the end
      of 1, 2, 3, 4 and 5 years were 96.3, 81.5, 79.2 and 18 per 100, respectively.
      Median survival time was about 37 months. Among women using the TCu380A IUD, the
      rate of termination due to bleeding was significantly higher than the rate of
      termination due to other causes. These findings indicate that family planning
      educators and health care providers should give more emphasis to counseling
      programs for women desiring IUD insertion and during follow-up.

PMID- 18817259
TI  - Aerophytic Cyanophyceae (cyanobacteria) from some Cairo districts, Egypt.
AB  - Twenty three aerophytic blue-green algal species were isolated and identified
      from 5 districts in Cairo, namely: Nasr City, Abassiya, Downtown, Maadi and
      Tebbin. Downtown contained the highest numbers of total algal species (13
      species) during the study throughout the years 2004-2005 in comparison to other
      districts. The composition of aeroalgal taxa varied with seasonal changes.
      Chroococcus limenticus, Lyngbya lagerheimii, Phormidium ambigum and Schizothrix
      purpurascens have been isolated during the both years 2004-2005, while the rest
      of algal species (nineteen species) have been trapped either in 2004 or 2005.
      Nostoc spp. is the most common isolate of all algal isolates during the study.
      Analysis of air pollutants such as SO2, NO2, suspended particles less than 10
      micro (PM10), black smoke and lead are also recorded. Downtown showed the highest
      concentration of SO2, NO2 and PM10 level during the present study in comparison
      to other sites. The interaction between air pollutants and aerophytic
      Cyanophyceae species was concerned.

PMID- 18817260
TI  - Study of water stress effects in different growth stages on yield and yield
      components of different rice (Oryza sativa L.) cultivars.
AB  - A field experiment was conducted during 2001-2003 to evaluate the effect of water
      stress on the yield and yield components of four rice cultivars commonly grown in
      Mazandaran province, Iran. In northern Iran irrigated lowland rice usually
      experiences water deficit during the growing season include of land preparation
      time, planting, tillering stage, flowering and grain filing period. Recently
      drought affected 20 of 28 provinces in Iran; with the southeastern, central and
      eastern parts of the country being most severely affected. The local and improved
      cultivars used were Tarom, Khazar, Fajr and Nemat. The different water stress
      conditions were water stress during vegetative, flowering and grain filling
      stages and well watered was the control. Water stress at vegetative stage
      significantly reduced plant height of all cultivars. Water stress at flowering
      stage had a greater grain yield reduction than water stress at other times. The
      reduction of grain yield largely resulted from the reduction in fertile panicle
      and filled grain percentage. Water deficit during vegetative, flowering and grain
      filling stages reduced mean grain yield by 21, 50 and 21% on average in
      comparison to control respectively. The yield advantage of two semidwarf
      varieties, Fajr and Nemat, were not maintained under drought stress. Total
      biomass, harvest index, plant height, filled grain, unfilled grain and 1000 grain
      weight were reduced under water stress in all cultivars. Water stress at
      vegetative stage effectively reduced total biomass due to decrease of
      photosynthesis rate and dry matter accumulation.

PMID- 18817261
TI  - Algal decolorization and degradation of monoazo and diazo dyes.
AB  - This study is to inspect how the variation of molecular structures and functional
      groups present in our models, monoazo dye (Tartrazine) and diazo dye (Ponceau),
      affects decolorization capabilities of green algae, cyanobacteria and diatoms.
      The results revealed that the removal of azo dyes was rapid at the initial period
      of study (3 days) and became slowly with the time (6 days). The maximum
      decolorization was observed at 5 ppm Tartrazine with S. bijugatus (68%) and N.
      muscourm after 6 days incubation. The reduction of color removal appears to be
      related to the molecular structure of the dyes and species of algae used. The
      culture of the diatom Nitzschia perminuta was completely died after 2 days of
      incubation. Azo reductase of algae, which is responsible for degradation of azo
      dyes into aromatic amine by breaking the azo linkage, was estimated. IR spectra
      represented a new peak at 3300 cm(-1) and a reduction in the azo band at 1642
      1631 cm(-1). In order to investigate the sorption behavior of algae, Langmuir
      equilibrium model was tested.

PMID- 18817262
TI  - Dynamics of population of five parasitic Monogeneans of Oreochromis niloticus
      Linne, 1757 in the dam of Loumbila and possible interest in intensive
      pisciculture.
AB  - The study of the gill fishes of 176 Oreochromis niloticus (L.) was undertaken in
      the dam of Loumbila (Burkina Faso), in order to obtain the first information on
      the dynamics of population of the Monogeneans parasites in a population of wild
      hosts. These data are essential in the search for means to avoid the enormous
      losses that often occur in intensive pisciculture. This analysis revealed the
      presence of five species of Monogeneans (Cichlidogyrus tilapiae, Cichlidogyrus
      halli, Cichlidogyrus thurstonae, Cichlidogyrus rognoni and Scutogyrus
      longicornis). On the levels of the recorded infestations, these species taken
      individually probably do not control the population of Oreochromis niloticus. In
      the dam of Loumbila, the fluctuations of parasitic abundances are neither
      seasonal nor cyclic. The size either does not have an influence on parasitism.
      However, the sex effect was noted with C. halli, the females thus were more
      infested than the males. O. niloticus is parasitized all the year, because the
      recruitment of these organisms, although relatively weak, is continuous; this
      logically results in their accumulation in this fish.

PMID- 18817263
TI  - Efficacy of dietetics in low resource communities: dietary intake and BMI of type
      2 diabetics living in Karachi before and after receiving dietician's guidance.
AB  - This study was planned to assess the dietary intake of diabetic subjects and kind
      of dietary modification they have made after individualised dietary guidance.
      Information on clinical and dietary profile of 200 subjects was recorded at first
      visit of BIDE. Dietary guidance was given by dietician. Second visit was done
      after 3 months. Subjects having adequate intake of fruit and vegetable, milk and
      meat was 68, 38 and 63% for males and 52, 40 and 35% for females, respectively.
      Only 20.4% males and 5.9% females had usual adequate consumption of the four food
      groups. Overall adequacy of diet improved for 11.1% of males and 27% of females.
      Weight reduction was observed in 54.8% of females and 32.2% of males. Rate of BMI
      reduction was significantly higher in the group who had reduced their caloric
      intake. This first of its kind study from Pakistan, has documented the efficacy
      of dietary guidance and highlighted the need for further attention to assure
      balanced intake of foods form various food groups.

PMID- 18817264
TI  - Tolerance of 42 bread wheat genotypes to drought stress after anthesis.
AB  - The present research characterized yield and yield components of 42 wheat
      genotypes after terminal drought stress. The experiment was in twice replicated
      simple rectangular lattice design, conducted at irrigated and terminal stress
      conditions during 2006-2007. These study genotypes had significant differences
      for grain yield at level of 1%. Genotypes 4057, Viking/5/Gds/4.., Sabalan and
      5041 respectively with 6.313, 6.159, 5.793 and 5.774 t ha(-1) had the highest
      yield and Gascogen has the lowest yield with 2.561 t ha(-1). Mean of total grain
      yield for under study genotypes was 5.628 t ha(-1) in non-stress and 3.305 t ha(
      1) in drought stress conditions. Drought stress decreased amount of grain yield
      2.323 t ha(-1) that was noticeable. Interaction of Genotype x environmental
      conditions was significant at probability level of 1% for grain yield. Yield of
      all genotypes in drought condition was lower than non-stress condition. Genotypes
      Viking/5/Gds/4/Anza/3/Pi.., Sabalan, 4061,4057 and 4041 had more yield in non
      stress condition and MV17/Zrn, Sabalan, Saysonz and 4032 in stress condition.
      Stress intensity pay attention to total grain yield was 42%. Genotypes
      Viking/5/Gds/4/.. and Sabalan had high grain yield and was better than other
      genotypes and controls (Toos and Crosse Shahi), according to GMP, STI and MSTI.
      And had the most amount of stress tolerance index as compared with other
      genotypes confirms this subject. Correlation of yield with other traits was not
      significant in non-stress condition. In drought condition, correlation of grain
      yield with 1000 grain weight and total number of tillers per plant was positively
      significant. ANOVA showed significant differences between osmotic pressures for
      coleoptile length, between genotypes for mean and maximum coleoptile length and
      between interactions of genotypes x osmotic pressures for mean and maximum
      coleoptile length. Mean comparisons showed the highest total, mean and maximum
      coleoptile length in -7 bar PEG+I ml L(-1) potassium humate treatments. Genotypes
      Sardari and Sabalan had the highest amounts of total, mean and maximum coleoptile
      length. With due attention to interaction genotype x osmotic pressures, genotypes
      Sardari, Sabalan and 4057 in -7 bar PEG+1 ml L(-1) potassium humate had the most
      amounts of noted characters than others. In conditions of this experiment,
      potassium humate caused increase in tolerance rate of genotypes against drought
      stress.

PMID- 18817265
TI  - Volatile components of Camellia sinensis inhibit growth and biofilm formation of
      oral streptococci in vitro.
AB  - This study aimed to evaluate the efficacy of semi fermented and non fermented
      Camellia sinensis extracts (Black and Green tea) and comparison between them
      against Streptococcus mutans ATCC 25175, S. mitis ATCC 9811 and S. sanguis ATCC
      10556 that are responsible for dental caries and bacteremias following dental
      manipulations. Minimum inhibitory concentrations of both tea extracts were
      assessed by Well diffusion and Broth dilution methods and examination of cell
      adherence (Biofilm inhibitory concentrations) was observed on glass slides under
      phase contrast microscope and colony counts from glass beads. Concentration of 1
      mg mL(-1) of semi fermented tea extract was completely biofilm inhibitor but
      biofilm formation by these bacteria was seen 7 days after treatment with 1 mg mL(
      1) of non fermented Camellia sinensis on glass beads and BIC for oral
      streptococci treated with this extract was 1.5, 2.5 mg mL(-1) of semi fermented
      and 3 mg mL(-1) of non fermented extracts had bactericidal effect on these
      bacteria. Semi fermented and non fermented Camellia sinensis extracts were able
      to prevent growth of oral streptococci. Therefore dental caries significantly
      reduce and the efficiency of semi fermented tea was higher due to rich content of
      volatile components rather than non fermented extracts.

PMID- 18817266
TI  - Physico-chemical behaviour of the fish lipid from Lepidocephalus guntea
      (Hamilton) and variation of lipid profile with size.
AB  - The fish lipid was extracted from the body muscle (edible portion) of fresh
      Lepidocephalus guntea (Ham.) fish and the lipid content of the fish in size-1
      (below 8.5 cm), size-2 (8.5-9.5 cm) and size-3 (above 9.5 cm) were found to be
      2.515, 3.013 and 3.455%, respectively. The specific gravity and refractive index
      of the lipid were found to be 0.93 at 30 degrees C and 1.467 at 31.5 degrees C,
      respectively. The saponification value, saponification equivalent, iodine value,
      peroxide value and acetyl value of the lipid were found to be 220.325, 254.624,
      96.05, 1.993 and 11.32, respectively. The acid value, percentage of free fatty
      acid as oleic and unsaponifiable matter present in the lipid were found to be
      2.005, 1.008 and 0.593, respectively. The fatty acid composition of the lipid was
      determined qualitatively and quantitatively by TLC and GLC. The analysis revealed
      that the fatty acid composition of the lipid lies between C14 to C20. The fish
      lipid of Lepidocephalus guntea (Ham.) was found to contain (average value)
      myristic acid (3.17%), palmitoleic acid (7.45%), palmitic acid (29.16%),
      linolenic acid (7.13%), linoleic acid (5.57%), oleic acid (22.93%), stearic acid
      (17.42%), arachidonic acid (7.17%) and arachidic acid in trace amount.

PMID- 18817267
TI  - An analysis on quality, colour, tissue texture, total soluble solid content,
      titratable acidity and pH of Santol fruits (Sandoricum koetjape Burm. F.) Merr.
      Pui Fai cultivar, grown in Northern Thailand.
AB  - This laboratory experiment was carried out at the Department of Agricultural
      Technology, Mahasarakham University, Northeast Thailand during June to October
      2007. The experiment aimed to search for the most appropriate harvesting age of
      fruits of Santol orchard plants with respect to colour, tissue texture, total
      soluble solid content, titratable acidity and pH of Santol fruits. A Randomised
      Complete Block Design (RCBD) with four replications was used. Each replication
      consisted of 10 fruits, thus a total of 160 fruits were used. The Santol fruits
      were harvested at different ages, i.e., 100, 115, 130 and 145 days after full
      bloom of flowers and these harvested ages were used as treatments, i.e., 100 for
      T1 (Control), 115 for T2, 130 for T3 and 145 for T4. The results showed that the
      most appropriate harvesting date for high quality Santol fruits was found with
      T4, i.e., 145 days after full bloom of flowers where Santol fruits of T4 gave the
      highest mean values of fruit length, diameter, fresh weight fruit(-1) of 10.71
      cm, 9.31 cm and 399.76 g, respectively. Yellowness of skin colour of fruits was
      evenly distributed. Total soluble solid content of pericarp, flesh tissue and
      seeds were highest for T4 with mean values of 13.93, 15.05 and 18.260 brix,
      respectively. Flesh texture density highly decreased with an increase in numbers
      of days after full bloom of flowers. Titratable acidity content in fruits was
      highly decreased with an increase in numbers of days after full bloom of flowers
      whereas a reverse was found with pH of fruit juices.

PMID- 18817268
TI  - Determination of yield stability in advanced potato cultivars as affected by
      water deficit and potassium humate in Ardabil region, Iran.
AB  - This experiment was done on the three potato cultivars [Agria (susceptible),
      Satina (semi-tolerant) and Ceaser (tolerant to water deficit)] and three
      irrigation treatments (after 30 mm evaporation from basin class A, after 60 mm
      evaporation + spraying by Potassium Humate, and after 60 mm evaporation from
      basin class A) for two locations in 2007. Experimental design was Split Plot with
      three replications. Potassium Humate spraying (250 mL ha(-1)) were done in three
      stages of emergence, before tuberization and during tuberization period. Combined
      analysis of variance showed that there were significant differences between
      locations, cultivars, irrigation treatments and location x cultivars interaction
      as effect on tuber yield. Comparison of means for irrigation treatments showed
      that spraying by Potassium Humate in stress condition induced increasing of tuber
      yield. Spraying by Potassium Humate in water deficit condition increased tuber
      yield up to 11.01 ton ha(-1). Ceaser had the highest tuber yield. It had higher
      tolerance to water deficit as well. Ceaser had a high potential in control and
      severe stress. Decrease in yield of Ceaser after 60 mm evaporation + spraying by
      Potassium Humate and after 60 mm evaporation from basin class A, relative to
      control (after 30 mm evaporation from basin class A) was 1.03 and 13.08 ton ha(
      1) but for Satina was 7.83 and 16.61 ton ha(-1), respectively. Satina had the
      lowest Environmental Variance, Environmental Variance Coefficient, Finlay and
      Wilkinson's and Eberhart and Russell's model and was the most stable cultivar.
      Lin and Binns parameter showed that Ceaser and Satina were the most stable
      cultivars. Results of GMP, STI and MSTI were very considerable and Ceaser and
      Satina had a high yield in water stress and control conditions.

PMID- 18817269
TI  - Alterations of domains in the plasmatic membrane due to damages of the
      perinuclear theca of pig preserved spermatozoa.
AB  - Samples of semen from 12 pigs, three from Yorkshire, Landrace, Duroc and Mexican
      Hairless each where obtained to study cryopreservation methods. Three stages of
      boar semen cryopreservation were evaluated: none (fresh stage), cooling at 5
      degrees C and freezing at -196 degrees C then thawing to 56 degrees C for 12 sec.
      Perinuclear theca damage and domain alterations were selected as indices of
      seminal quality, as measured by electronic and fluorescence microcopy,
      respectively according to two lineal models considering by separately the effect
      of semen preservation and breed. Integrity and absence of perinuclear theca
      significantly (p < 0.001) decreased and increased, respectively according to a
      decrease in temperature of cryopreservation, from 87.4 to 58.8% and from 0.8 to
      26.2%, respectively. This same significant (p < 0.001) effect was found for
      acrosomal and post-acrosomal membrane distribution of domains, from 92.1 to 76.8%
      and from 3.1 to 13.1% in this same order. Slight but highly significant (p <
      0.001) differences were observed when theca integrity was evaluated as affected
      by breed, with highest and lowest values for Yorkshire and Pel6n Mexicano pigs,
      respectively. No breed effect was encountered for presence of acrosomal domains.
      A strong interdependence was found between perinuclear theca damage and domain
      distribution. In this connection, a highly significant (p < 0.001) positive,
      interdependence was observed between the theca damage and acrosomal domain (r =
      0.87), while this same relationship was although highly significant (p < 0.001),
      negative in nature for equatorial and post-acrosonal domains (r = -0.77 and 
      0.85, respectively). This experiment confirmed that cryopreservation methods may
      severely affect semen quality of pigs and that genotype may further influence
      these same indices. More research is needed for improving methods of preservation
      of pig semen quality, from the point of view of perinuclear theca and domain
      characteristics of spermatozoa.

PMID- 18817270
TI  - Kinetics of ascorbic acid degradation in un-pasteurized Iranian lemon juice
      during regular storage conditions.
AB  - The aim of this research was to determine shelf life stability of un-pasteurized
      lemon juice filled in clear or dark green glass bottles. Presence of light, time
      and temperature affect the ascorbic acid retention in citrus juices. Bottles were
      stored at room temperature (27 +/- 3 degrees C) and in the refrigerator (3 +/- 1
      degrees C). Total soluble solids, total titrable acidity and pH value were
      measured every three weeks and analysis was carried out on ascorbic acid content
      by means of titration method in the presence of 2,6-dichlorophenol indophenol.
      The study was carried out for 12 weeks after which slight changes in color, taste
      and apparent texture in some samples were observed and ascorbic acid content
      reduced by 50%. Soluble solids content, pH value and total acidity were 5.5
      degrees Brix, 2.73 and 5 g/100 mL, respectively which appeared not to be
      significantly influenced by storage time or conditions. Ascorbic acid content
      initially at 38.50 mg/100 mL was sharply reduced to about 22 mg/100 mL within the
      first three weeks of storage. The final ascorbic acid content of all samples was
      about 15 mg/100 mL. The deteriorative reaction of ascorbic acid in the juice at
      all conditions followed a first-order kinetic model with activation energy of 137
      cal mol(-1).

PMID- 18817271
TI  - Shortening transplantation periods of potato plantlets by use of potassium humate
      and kadostim and their effects on mini-tuber production.
AB  - Plantlets produced from meristem culture of six advanced cultivars (Agria,
      Advanced clone 397007-9, Marfona, Sante, Satina and Ceaser) propagated by single
      node cuttings arranged in a RCBD base factorial design with ten replications.
      Factor A was plantlets produced from meristem culture of advanced cultivars and
      factor B was seven treatments (four concentrations of potassium humate as 0.5, 1,
      1.5 and 2 mL, one concentrations of kadostim as 1 mL, compound concentration of
      potassium humate and kadostim as 1 ml L(-1) MS media culture and without them as
      control). Produced plantlets transplanted into the planting beds of Pitmass
      (Biolan) with punce (1:1 v/v) in the greenhouse. Some of traits measured such as
      average weight and number of mini-tuber per plant after harvesting. Results of
      analysis of variances showed the significant differences between effects of
      kadostim and potassium humate on advanced cultivars, for transplantation into the
      greenhouse, stem solidity and rhizo-genesis characters. So transplantation days
      decreased from 30 to 13 days in MS media culture with compound of potassium
      humate + kadostim by concentration of 1 ml L(-1) MS media culture, also decreased
      to 15 days in MS media culture with kadostim by concentration of 1 ml L(-1) MS
      media culture and also decreased to 22 days in MS culture with potassium humate
      by concentration of 1 and 1.5 ml L(-1) MS media culture and plantlets had the
      highest stem solidity and better rhizo-genesis in all of treatments. Agria, Sante
      and Marfona transplanted earlier and Ceaser transplanted later than others to the
      greenhouse. Compound concentration of potassium humate and kadostim 1 ml L(-1) MS
      media culture had the highest number of mini-tubers per plant and potassium
      humate 0.5 ml L(-1) MS and Kadostim 1 ml L(-1) MS had the highest mini-tuber
      weight per plant and average of mini-tuber weight per plant. Agria had the
      highest number and average of weight of mini-tubers per plant. Potassium humate
      0.5 ml L(-1) MS in satina, kadostim 1 ml L(-1) MS in marfona and potassium humate
      + kadostim 1 ml L(-1) MS in Agria had the highest number of mini-tubers per
      plant. Increasing rate of weight and number of mini-tubers per plant with
      potassium humate and kadostim in all of advanced cultivars were more than
      control.

PMID- 18817272
TI  - Effect of molybdenum and sulphur on copper status and mohair quality in Merghoze
      goat.
AB  - This study was made on the effects of a normal diet containing 12.8 mg Cu kg(-1)
      DM which added gradually molybdenum and sulphur on the copper status and fibre
      quality in eight 1-year Merghoze goat. One group (n = 4 mean weight 31 +/- 2.0
      kg) was treated with Mo and S supplements for 20 weeks, the second group (n = 4
      mean weight 32 +/- 2.1 kg) served as controls. In addition of blood sampling for
      measuring copper status in plasma, the copper content and quality of fleeces were
      measured every 6 weeks. Mohair measurements were carried out by taking patch
      samples (10 x 10 cm2) from the mid-side area of the goat. The analytical set
      consists of plasma copper concentrations (Pl Cu), Trichloroacetic acid soluble
      copper concentrations (TCA-Cu), and fleece copper content. The results indicated
      that the addition of 20-30 mg Mo and 2-2.5 g S kg(-1) DM to the normal diet did
      produce sub clinical copper deficiency in treated goats. One such visual symptom
      was the loss of fleeces pigmentation and poorer crimp being observed. The Pl Cu
      minus TCA-Cu plasma became more than 2 microM in the blood of treated goat,
      indicating that there was a significant thiomolybdate formation in the body. The
      results showed that there was a significant decrease in Pl Cu (p < 0.05) along
      with a significant increase in thiomolybdate (MoS) production after 4 months. The
      sub clinical signs of copper deficiency and mohair quality are likely to be from
      high molybdenum intake and thiomolybdate formation in the body.

PMID- 18817273
TI  - The potential of using insecticidal properties of medicinal plants against insect
      pests.
AB  - In this study, botanicals extracted from two the species of family
      Scrophulariaceae, Verbascum cheiranthifolium Boiss and Verbascum speciosum
      Schard, were examined for their effect on mortality and progeny production
      against adults of Sitophilus oryzae (L.). The plant extracts were applied at five
      dose rates, which 0.25, 0.5, 1.0, 2.0 and 3% (w/v). Adults of S. oryzae was
      exposed to the treated wheat at 25 degrees C and 65% RH and mortality was
      assessed after 24 h, 48 h, 7 day, 14 day and 21 day of exposure. Then all adults
      were removed and the treated substrate remained at the same conditions for an
      additional 45 day after this interval, the commodity was checked for progeny
      production. In use two extracts the mortality of adults increased with the
      increase of dose and exposure interval so that; mortality was 100% after 21 days
      of exposure at the highest dose rate. Results indicated that applied of V.
      cheiranthifolium extract was more effective than V. speciosum against adult
      insects. Interestingly, in two cases complete suppression (100% reduction) of the
      progeny production (F1) was observed in the treated wheat than in control even in
      the lowest dose rate. Therefore, our results indicate that these medicinal plants
      can be used for protection of stored grain from infestations of stored-product
      insect pests.

PMID- 18817274
TI  - Salinity effects on compatible solutes, antioxidants enzymes and ion content in
      three wheat cultivars.
AB  - In order to study effects of different salinity levels on antioxidant enzyme
      activities, catalase (CAT), ascorbate peroxidase (APX) and guaiacol peroxidase
      (GPX) associated with compatible solutes, proline and carbohydrate and mineral
      nutrient content in shoots, sodium and potassium, in three wheat cultivars an
      experiment was conducted as completely randomized 3 x 4 factorial design with
      three replicates in a greenhouse. Three wheat cultivars (Pishtaz, Kavir and
      Hamon), that differ in their salt tolerances, were grown in four different
      salinity levels (S0 = control, S1 = 100, S2 = 200 and S3 = 300 mM NaCl). Twenty
      days after wheat cultivars subjected to salt stress, data showed salinity stress
      induced increase in the antioxidant enzyme activities. Among the cultivars,
      salinity stress decreased leaf-APX but increased the activities of leaf-GPX in
      Pishtaz cultivar. Our results showed a positive correlation between praline
      accumulation and Leaf-APX (r2 = 0.56), Leaf-GPX (r2 = 0.63) and Leaf-CAT (r2 =
      0.73). In these cultivars, in their shoots Na+ showed an increase in
      concentration with salinity that approximately matches a decrease in K+
      concentration. It seems that Na+ concentrations in the shoot may have had a more
      significant effect on plant antioxidant enzyme activities and compatible solutes
      such as proline and carbohydrates. These results indicated which in wheat under
      salinity stress antioxidant enzymes and compatible solutes help to plant
      adaptation. In this study we found a positive correlation between Na+
      concentration in the shoots and the antioxidant enzyme activities and compatible
      solutes in the leaves.

PMID- 18817275
TI  - Growth and some physiological parameters of four sugar beet (Beta vulgaris l.)
      cultivars as affected by salinity.
AB  - The comparative responses of certain biochemical and physiological
      characteristics to salinity were studied in 4 cultivars of sugar beet (Beta
      vulgaris L.) plants. Eight weeks old plants were treated with NaCl at 0, 25 and
      50 mM in nutrient solutions. Plants were grown under controlled environment and
      harvested after 3 weeks for measurements of biochemical and physiological
      parameters. Results showed that in 25 mM NaCl for cultivars of ET5 and C3-3,
      soluble sugars in leaves, photosynthetic rate and growth parameters were
      significantly increased as compared to those of other cultivars. In 50 mM NaCl
      photosynthetic rate and soluble sugars were significantly increased only in ET5
      cultivar as compared with those of others. Results indicated that in 25 mM NaCl,
      ET5 cultivar showed high growth responses and tolerated to 50 mM NaCl.

PMID- 18817276
TI  - Evaluation of glucose-6-phosphate dehydrogenase deficiency without hemolysis in
      icteric newborns at Mazandaran province, Iran.
AB  - This study was carried out with the aim of evaluating the prevalence of G6PD
      deficiency, the prevalence of hemolysis with enzyme deficiency and determining
      the severity of icterus in the hospitalized newborns in our hospital. This
      prospective descriptive study has been conducted on 1018 icteric newborns
      admitted to the Bo-Ali Hospital from 2004 to 2007. The dataset included: age,
      sex, total and direct bilirubin, hemoglobin, reticulocyte count, blood group and
      Rh of mother and newborn, direct Coombs, G6PD level and the type of treatment.
      All data was analyzed by using statistical method. From 1018 neonates, 138
      neonates (13.6%) were found to have G6PD deficiency. The male to female ratio was
      3 to 1 (104 male and 34 female neonates). From 138 neonates with G6PD deficiency,
      hemolysis was seen in 15 neonates (10.9%) and the rate of G6PD deficiency with
      hemolysis was 1.6%. Out of 138 patients with G6PD deficiency, 2 patients (0.2%)
      had blood exchange transfusion. In this study the prevalence of G6PD deficiency
      in icteric newborns was considerably high and most of them were non hemolytic, so
      we recommend G6PD test as a screening program for every newborn at the time of
      delivery.

PMID- 18817277
TI  - The effect of iron deficiency anemia on intelligence quotient (IQ) in under 17
      years old students.
AB  - The aim of this study was to evaluate the effects of iron deficiency on
      intelligence of 11-17 years students. This study conducted on the 540 students
      (11-17 years) that educated at guidance and high school of Boroujerd city.
      Laboratory investigations were included serum iron, TIBC (total iron binding
      capacity) and ferretin. Riven matrix was used in order to determine intelligence
      quotient. Data were analyzed using SPSS 13 and chi2 and t-tests. Results showed
      that 78 (14.4%) students had iron deficiency and 14 (25.9%) had iron deficiency
      anemia. There was no significant difference between different sexes for iron
      deficiency distribution (p > 0.05), while iron deficiency anemia was
      significantly higher in girls as compared with boys (p > 0.05). Mean quotient was
      115 +/- 12.1 in iron deficiency students, while it was 113.7 +/- 13.9 in patients
      without iron deficiency. There was also no significant difference between normal
      and iron deficient students for intelligence quotient (p > 0.05).

PMID- 18817278
TI  - Full-thickness skin avulsion of right leg following car accident trauma.
AB  - The report presents a 24 year-old man who admitted at the orthopedic center with
      full-thickness skin avulsion of the right leg, due to his leg being caught under
      the wheel of a truck and subsequently traumatized. The day after injury, plastic
      and reconstructive surgery consult was done. After thoroughly irrigation, the 20
      cm laceration was repaired above the knee. There was full-thickness skin necrosis
      below the knee down to the dorsal surface of the right leg (atypical form of skin
      avulsion). Debridment and graft was performed for the first stage. During the
      second stage, re-grafting was performed and the gasterocnemious flap was
      transposed to cover the Tibia bone. This study confirms early Plastic and
      reconstructive surgery consult from the trauma of lower extremities associated
      with skin lesion.

PMID- 18817279
TI  - Animal genomics for animal health. Preface.

PMID- 18817280
TI  - Animal genomics for animal health. Opening remarks.

PMID- 18817281
TI  - The future impact of animal genomics in animal health research.
AB  - The first International Symposium on Animal Genomics for Animal Health (AGAH)
      provided an excellent venue for scientists working in the field of genomics to
      interact with animal health experts. This paper provides an introduction to
      genome-enabled tools and highlights some of the research projects in the AGAH
      proceedings. A brief review of animal genomes, the next generation of genetic
      markers, and the versatility of genome-enabled technologies and their many
      applications are discussed.

PMID- 18817282
TI  - DNA-based animal models of human disease: from genotype to phenotype.
AB  - Biomedical research utilizes animal models to elucidate human disease processes
      at the cellular and molecular level and for the development of new therapies.
      Traditionally, mammalian models have been limited to the mouse, primarily because
      of well characterized genetic lines and the ability to manipulate the genome to
      directly test hypotheses regarding causal mutations and disease phenotypes. The
      emerging availability of genome sequences of other mammals (bovine, canine,
      equine, feline, and porcine) now permits utilization of the mammal in which the
      phenotype best approximates the human condition. Equally important is the use of
      somatic cell nuclear cloning (SCNT) coupled with targeted germline manipulation
      to create animals to resolve the molecular mechanisms of the disease state. Our
      efforts have focused on the pig, which has emerged as an important biomedical
      mammalian model due to its closer physiology to humans. The utility of porcine
      genetically-defined tumour, cardiovascular and neurological disease models is
      described.

PMID- 18817283
TI  - Exploiting genomics to improve animal health.
AB  - The research area of animal genomics is moving now from its sequencing era into
      an integrativefunctional genomics era. Thefast growing sequence information of
      animal genomes provides exiting opportunities for improving animal health traits
      by genomics-assisted breeding approaches. In addition, data from functional
      genomics studies offers deeper insight into the biological mechanisms that
      underlie animal health phenotypes. Understanding host-pathogen relationships, for
      example, promises to forward the integration of health genetics into breeding
      programmes and the development of new tools and strategies for the diagnosis,
      prognosis, treatment and prevention of infectious diseases. Similarly, increased
      knowledge on nutrient-gene interactions provides information on the effects of
      nutrients on biological processes. This knowledge may be used to redefine and
      optimize the nutritional needs of healthy animals. In this paper, prospects,
      challenges, and requirements of animal genomics research for improving animal
      health will be presented.

PMID- 18817284
TI  - Improving pig health through genomics: a view from the industry.
AB  - Health is one of the most important contributors to animal welfare, productivity
      and profitability in pig production today. For the past 30 years, pig breeders
      have focused on genetic improvement of lean growth, feed efficiency, meat quality
      and reproduction. However, in recent years, selection objectives have been
      broadened to include livability, robustness and disease resistance. A DNA marker
      for selection of resistance to F18+ E. coli has been available for several years.
      This marker decreases mortality and improves growth on farms experiencing post
      weaning scours and/or oedema disease. However, for most diseases affecting
      intensive production systems such as porcine reproductive and respiratory
      syndrome (PRRS), porcine circovirus type 2-associated diseases (PCVAD),
      Haemophilus parasuis, and swine influenza virus, resistance is a complex and
      polygenic trait. Selection for improved resistance to these diseases will be
      incremental and require use of multiple markers in complex breeding schemes.
      Novel technologies such as pig gene microarrays, single nucleotide polymorphism
      (SNP) panels and advanced bioinformatics are being used to identify new health
      candidate genes for these economically important diseases. Lagging behind,
      however, is availability of large DNAdatasets from pedigreed populations with
      accurately measured health phenotypes that are needed to identify associations
      between SNPs and health traits. Increased focus on datasets with health traits
      will be the key to finding useable discoveries with new genomics technologies.
      Currently, the industry uses dozens of SNP markers to increase the accuracy of
      selection for complex breeding objectives, including disease resistance. As the
      pig genome is sequenced and barriers to genotyping thousand of markers are
      eliminated, genomic selection for health traits will receive increasing attention
      from commercial breeders.

PMID- 18817285
TI  - Proteomic dissection of viral pathogenesis.
AB  - Many factors play into the complexity of viral pathogenesis. Understanding viral
      pathogenesis is key to developing vaccines and treatments for viral diseases. One
      emerging area of research is proteomics, which is the study of the protein
      complement and functions of the genome. Many different proteomic approaches have
      been utilized by researchers worldwide to further elucidate viral pathogenesis.
      For example, a high throughput MALDI-MS approach was recently employed to study
      the antigenicity of the influenza virus. Another study utilized MALDI-TOF MS and
      liquid chromatography MS/MS of proteins present in lipid droplets of hepatoma
      cell lines to identify proteins involved in the pathogenesis of hepatitis C virus
      that contribute to its carcinogenic properties. In conjugation with MS, yeast two
      hybrid systems have also been shown to be useful in identifying potential host
      receptors of various viruses as well as revealing the interaction of viral
      proteins with other host proteins and viral proteins. In this review, the focus
      is on various proteomic approaches to dissecting the mechanisms of viral
      pathogenesis.

PMID- 18817286
TI  - Integrated immunogenomics in the chicken: deciphering the immune response to
      identify disease resistance genes.
AB  - Resistance to infection takes place at many levels, and involves both non
      specific and specific immune mechanisms. The chicken has a different repertoire
      of immune genes, molecules, cells and organs compared to mammals. To understand
      the role of any disease resistance gene(s), it is therefore important to
      understand these different repertoires, and the bird's response to a particular
      pathogen. Our studies focus on the innate immune response, as responses of
      macrophages from inbred lines of chickens, and heterophils from commercial birds,
      correlate with resistance or susceptibility to Salmonella infection with a
      variety of Salmonella serovars and infection models. To map disease resistance
      genes, we are using a combination of expression quantitative trait loci (eQTLs)
      from microarray studies, allied with whole genome SNP arrays (WGA) and a
      candidate gene approach. There are over 500 human genes with the Gene Ontology
      term "innate immunity". We have identified over 400 of these genes in the chicken
      genome, and are actively identifying informative SNPs in them. The segregation of
      6000 WGA SNPs across all of our inbred lines was also assessed, which should
      yield approximately 900 informative SNPs for a cross between any two lines. The
      initial focus of these studies is on mapping resistance genes in our inbred
      lines, but the studies will be extended to commercial flocks.

PMID- 18817287
TI  - Quantitative genetic and functional genomics approaches to investigating parasite
      disease resistance and protective immune mechanisms in avian coccidiosis.
AB  - A major challenge for the commercial poultry production is controlling enteric
      disease-causing pathogens in the absence of prophylactic drugs. Although
      traditional genetic approaches have contributed to enhanced efficiency of poultry
      production and increased the ability of the industry to provide safe, high
      quality, and low cost meat products to consumers, economic losses due to enteric
      diseases remains a significant problem. Therefore, there is a need to develop
      alternative control strategies against poultry enteric pathogens of economic
      importance. Recent advances in molecular genetics and functional genomics are now
      allowing for rapid progress in understanding the molecular mechanisms of disease
      resistance against major infectious agents of poultry. It is anticipated that
      identifying the nature of host-pathogen interactions will facilitate the
      development of novel vaccines and therapeutics. In this paper, recent progress in
      identifying genes that influence resistance to avian coccidiosis, the most
      economically important disease of poultry, will be discussed. This work provides
      an excellent example of how the integration of new molecular genetic and
      functional genomics tools increases our knowledge of the mechanism of genetic
      resistance to complex diseases.

PMID- 18817288
TI  - Identification of genes involved with tick infestation in Bos taurus and Bos
      indicus.
AB  - Tick resistant cattle could provide a potentially sustainable and environmentally
      sound method of controlling cattle ticks. Advances in genomics and the
      availability of the bovine genome sequence open up opportunities to identify
      useful and selectable genes controlling cattle tick resistance. Using
      quantitative real-time PCR and theAffymetrix bovine array platform, differences
      in gene expression of skin biopsies from tick resistant Bos indicus (Brahman) and
      tick susceptible Bos taurus (Holstein-Friesian) cattle following tick challenge
      were examined. We identified 138 significant differentially-expressed genes,
      including several immunologicallhost defence genes, extracellularmatrix proteins,
      and transcription factors as well as genes involved in lipid metabolism. Three
      key pathways, represented by genes differentially expressed in resistant
      Brahmans, were identified; the development of the cell-mediated immune response,
      structural integrity of the dermis and intracellular Ca2+ levels. Ca2+, which is
      implicated in host responses to microbial stimuli, may be required for the
      enhancement or fine-tuning of transcriptional activation of Ca2+ -dependant host
      defence signalling pathways.

PMID- 18817289
TI  - Genomics approaches to study the biology underlying resistance to trypanosomiasis
      -some unexpected lessons.
AB  - An international multidisciplinary consortium is conducting a programme of
      research on the host response to trypanosome infection. This builds upon
      quantitative trait loci (QTL) mapping which identified genome regions influencing
      susceptibility to pathology following T. congolense infection in both cattle and
      mice. The approach uses expression analysis to examine the response of both
      susceptible and resistant strains and a series of novel informatics tools to
      identify pathways which are activated as a result of challenge, and those which
      are differentially used by resistant and susceptible strains. Of particular
      interest are those pathways which simultaneously satisfy both criteria, i.e. are
      significantly differentially activated and contain genes within QTL regions.
      However, it is important to stress that it is not required that the genes within
      the QTL region are differentially expressed themselves.

PMID- 18817290
TI  - Bovine viral diarrhoea virus infection alters global transcription profiles in
      bovine endothelial cells.
AB  - Bovine viral diarrhoea viruses (BVDV) are significant pathogens of cattle
      worldwide. These viruses exist in both non-cytopathic and cytopathic biotypes.
      Non-cytopathic BVDV can establish persistent lifelong infections in cattle and
      are a frequent contaminant of biological reagents such as cell cultures and
      foetal bovine serum. We identified commercially available bovine aortic
      endothelial cells (BAECs) contaminated with BVDV. In this study, to determine if
      BVDV alters endothelial gene transcription patterns, serial analysis of gene
      expression (SAGE) was used to compare gene expression profiles from uninfected
      and BVDV contaminated BAEC. SAGE is an open ended, quantitative method for
      characterizing global patterns of transcription. Comparison of expression
      profiles of BVDV-contaminated and noninfected cells revealed significant
      increases in the transcription of many genes including P-selectin, tryptophan
      tRNA synthetase and prostaglandin D2 synthase. These changes were validated by
      real-time PCR. Additionally, real-time PCR demonstrated that the response to LPS
      and dsRNA by contaminated cells, as well as cells acutely infected with
      noncytopathic BVDV, is altered. The altered response may be through the high
      level of expression of A20 and inhibition of activation of NF-kappaB. BAECs are
      commonly used as a model to study endothelial cell function in many different
      systems. As shown here, transcriptional and probable protein changes resulting
      from BVDV infection significantly alter cellular responses and may have a
      profound impact on experimental outcome. Transcriptomic analysis provided the
      initial clues leading to the characterization of this altered function.

PMID- 18817291
TI  - A combined transcriptomic approach to analyse the dialogue between pseudorabies
      virus and porcine cells.
AB  - The pseudorabies virus (PrV), a porcine Alphaherpesvirus, is a good model for the
      study of virus-host cell dialog. As PrV has a strong tropism for mucous
      epithelial cells, we chose to follow in vitro the PrV time course-infection of
      porcine PK15 cells. The viral and cellular transcriptome modifications were
      simultaneously analysed using a combined SLA/PrV cDNA microarray, the porcine
      Qiagen-NRSP8 oligonucleotides microarray and real time quantitative PCR.Ahigh
      increase in viral gene expression was found from 4 h post-infection (PI),
      concomitantly to the first viral progeny and most viral genes were differentially
      expressed 12 h PI. No early global cellular shutoff was observed but many
      cellular genes were downregulated between 8 and 12 h PI, when UL41 transcripts
      encoding the virion shutoff protein, were first detected. Several genes involved
      in the MHC class I mediated antigenic pathway were downregulated including SLA
      la, TAP1, TAP2, PSMB8 and PSMB9 genes. These results suggested that PrV prevents
      the viral antigen presentation by epithelial cells to cytotoxic T lymphocytes by
      decreasing transcription levels of SLA Ia mediated antigenic pathway genes. Other
      genes involved in the immune response, the apoptosis pathway, nucleic acid
      metabolism and cytoskeleton also appeared to be regulated during PrV infection.
      The combined approach will help to decipher host response evasion strategies
      developed by PrV and to study early cellular modifications.

PMID- 18817292
TI  - Computational integration of structural and functional genomics data across
      species to develop information on the porcine inflammatory gene regulatory
      pathway.
AB  - We are investigating the porcine gut immune response to infection through gene
      expression profiling. Porcine Affymetrix GeneChip data was obtained from RNA
      prepared from mesenteric lymph node of swine infected with either Salmonella
      enterica serovar Typhimurium (ST) or S. Choleraesuis (SC) for 0, 8, 24, 48 or 504
      hours post-inoculation (hpi). In total, 2365 genes with statistical evidence for
      differential expression (DE; p < 0.01, q < 0.26, fold-change > 2) between at
      least two time-points were identified. Comparative Gene Ontology analyses
      revealed that a high proportion of annotated DE genes in both infections are
      involved in immune and defence responses. Hierarchical clustering of expression
      patterns and annotations showed that 22 of the 83 genes upregulated from 8-24 hpi
      in the SC infection are known NF-kappaB targets. The promoter sequences of human
      genes orthologous to the DE genes were collected and TFM-Explorer was used to
      identify a set of 72 gene promoters with significant over-representation of NF
      kappaB DNA-binding motifs. All 22 known NF-kappaB target genes are in this list;
      we hypothesize that the remaining 51 genes are un-recognized NF-kappaB targets.
      Integration of these results and verification of putative target genes will
      increase our understanding of the porcine response pathways responding to
      bacterial infection.

PMID- 18817293
TI  - EST-based gene indices for the cattle fever tick, the horn fly, and the screwworm
      fly.
AB  - The southern cattle tick, Rhip,cephalus (Boophilus) microplus, the horn fly,
      Haematobia irritans, and the New World screwworm, Cochl,omyia hominivorax, are
      economically important parasites of cattle throughout the world. Understanding
      the biology and genomics of these pests is critical to developing novel control
      methods. We developed EST sequence databases for these parasites and used
      bioinformatic analysis to identify conceptual open reading frames and assigned
      Gene Ontology (GO) terms to those database transcripts that had informative
      BlasIX hits. Bloinformatic analysis showed that a large fraction of the tick
      database entries have no clear matches in other sequenced genomes. Several
      putative tick G protein-coupled receptors (GPCRs) were identified that mightserve
      as starting points to develop novel control technologies.

PMID- 18817294
TI  - Comparison of transcriptional changes associated with E. acervulina and E. maxima
      infections using cDNA microarray technology.
AB  - Enhanced understanding of host-pathogen interactions at local sites of infection
      will extend our knowledge of disease pathogenesis and will facilitate the
      development of novel preventive methodologies against many infectious diseases of
      economic importance. In the current study, a 9.6K avian intestinal
      intraepithelial lymphocyte cDNA microarray (AVIELA) was developed to compare the
      local transcriptional profiles following primary and secondary infections with
      two major Eimeria parasites, E. acervulina (EA) and E. maxima (EM), which infect
      the intestinal duodenum and jejunum, respectively. Gene Ontology analyses showed
      that EAinfection primarily induced genes associated with lipid metabolism and
      intracellulartrafficking whereas EM infection upregulated the genes involved in
      protein biosynthesis and metabolism, and downregulated apoptosis related genes.
      Following primary EA infection, there was a significantly enhanced expression of
      genes involved in the signal pathway of T cell activation and cytoskeletal
      regulation. Thus, the AVIELA array provides a valuable tool for investigating
      host-pathogen interactions in avian coccidiosis and allows for the comparison of
      the transcriptional regulations induced by species of Eimeria that infect
      different areas of the intestine.

PMID- 18817295
TI  - Differential immune-related gene expression in two genetically disparate chicken
      lines during infection by Eimeria maxima.
AB  - Two M5.1 and M15.2 B complex congenic lines of Fayoumi chickens were evaluated
      for body weight loss and faecal oocyst counts as parameters of avian coccidiosis.
      M5.1 chickens exhibited resistance to E. maxima compared with M15.2. To correlate
      the differential responses of the M5.1 and M15.2 lines to E. maxima infection
      with cellular immune responses, the expression levels of mRNAs encoding 14 immune
      related molecules were measured by quantitative RT-PCR in intestinal
      intraepithelial lymphocytes (IELs) and splenocytes at 0, 3, 4, and 5 days
      following parasite infection. Intestinal IELs from M5.1 chickens expressed higher
      levels of transcripts encoding interferon gamma (IFNG), interleukin-lbeta (1L1B),
      IL6, IL8, IL12, IL15, IL17A, inducible nitric oxide synthase (iNOS), and
      lipopolysaccharide-induced tumour necrosis a factor (LITAF), and lower levels of
      mRNAs for IFNA, IL10, IL17D, NK-lysin (NKL), and tumour necrosis factor
      superfamily 15 (TNFSF15) at 3 days post infection, compared with the M15.2 line.
      In the spleen, E. maxima infection was associated with higher expression levels
      of IFNA, and IL15 and lower levels of IL6, IL17D, and IL12 in M5.1 compared to
      M15.2 birds. Using an intestinal IEL cDNA microarray, the differential dynamics
      of gene expression in the gut of M5.1 and M15.2 chickens following experimental
      coccidiosis were evident. In particular, the genes encoding lymphotactin and
      parathymosin were expressed at significantly higher levels in M5.1 compared with
      M15.2 line chickens. In conclusion, genetic determinants within the chicken major
      histocompatibility complex (MHC) B complex influence resistance to E. maxima
      infection by controlling the local and systemic expression of immune-related
      cytokine and chemokine genes.

PMID- 18817296
TI  - Transcriptional response of chicken macrophages to Salmonella enterica serovar
      enteritidis infection.
AB  - The transcriptional profiles of chicken macrophages (HD11) infected with
      Salmonella enterica serovar Enteritidis (SE) were analyzed by using an avian
      macrophage microarray and real time RT-PCR. Out of 4906 array elements
      interrogated, 269 genes exhibited a 2 fold change (P < 0.001) over a 24 h time
      course. Genes coding for proinflammatory cytokines, CC and CXC chemokines, and
      chemokine ligand were upregulated; whereas genes associated with transcription,
      cell adhesion and proliferation were downregulated. Most transcriptional changes
      occurred at 5 hours post-inoculation (hpi), with more genes downregulated than
      upregulated.At 5 hpi, the levels of gallinacin 1, lymphotactin, RhoA, and MHCIB2M
      transcripts were significantly decreased. In contrast, the levels of Cdc42 and
      MHCIIBLB2 mRNA were elevated. Infection of HD11 cells with mutant SE strains
      carrying an inactivated type three secretion system (TTSS1 or TTSS2) induced
      significantly higher levels of CCL4, K203, lymphotactin, and RhoA than wild type
      SE. In conclusion, chicken macrophage genes belonging to diverse functional
      classes were transcriptionally modulated by SE and selective modulation of host
      innate responses involved the effectors of TTSS1/2.

PMID- 18817297
TI  - Unique co-expression of immune cell-related genes in IBDV resistant chickens
      indicates the activation of specific cellular host-response mechanisms.
AB  - Infectious bursal disease virus (IBDV) causes highly contagious,
      immunosuppressive disease that leads to high mortality in young chickens. The
      purpose of this study was to look for the genetic regulation of the immune acute
      immune response to IBDV in our selected lines. Chicks of a F2 generation of two
      lines divergently selected for early high (HH) or low (LL) antibody (Ab) response
      to Escherichia coLi vaccination were challenged with virulent IBDV. Viral load in
      infected bursae was used to determine resistant (R) and susceptible (S) birds. By
      using a 13K chicken cDNA microarray, and pooled spleen mRNA of R, S and non
      challenged, control (C) chicks, several genes were identified with differential
      expression associated with host resistance to IBDV. These genes were also
      subjected to RT-PCR on individual samples to verify the results obtained from
      microarrays. The major finding was the co-upregulation of seven genes--ETS2,
      H963, RGS1, ABIN-2, CREM/ICER, DUSP1 and CXCR4- in several R, but not S or C
      individuals, and characterized by a high correlation of expression levels.
      Resistance also generally coincided with reduced transcript levels of acute-phase
      serum amyloid A (A-SAA) and increased levels of IL-8. Based on reported functions
      of these genes, these findings suggest that resistance was mediated by the
      activation of specific cellular mechanisms, indicated by increased activity of
      splenic macrophages and T-lymphocytes 3 days post-challenge.

PMID- 18817298
TI  - Physiological interactions between the endocrine and immune systems shown in gene
      analysis in pigs.
AB  - A number of observations support the concept of important physiological
      interactions between the endocrine and immune systems. It could be confirmed that
      hormones secreted by the neuroendocrine system play an important role in
      communication and regulation of the cells of the immune system. Among protein
      hormones, this has been most clearly documented for prolactin (PRL), growth
      hormone (GH), and insulin-like growth factor 1 (IGF-1). A number of traits of the
      immune response in a Duroc x Berlin Miniature pig family (DUMI) were examined.
      The haemolytic complement activity in the classical complement pathway (CH50) and
      the alternative pathway (AH50)was examined at eight different time points in pigs
      that were vaccinated with different vaccines. Single nucleotide polymorphism
      (SNP) genotyping was employed to genotype the DUMI F2 animal for growth hormone
      (Gh), growth hormone releasing hormone (Ghrh), pituitary-specific transcription
      factor 1 (Pit1), and prolactin receptor (Prlr) loci, and also a microsatellite
      within insulin-like growth factor 1 (Igf1). Using a family-based association test
      (FBAT) program, a highly significant association of Gh, Pit1, and Prlr to AH50 (p
      < or = 0.01) and a significant association of Pit1 to CH50 (p < or = 0.05) were
      found. Using the SAS system for mixed model, a highly significant association of
      Gh, and Igf1 to AH50 and CH50 (p < or = 0.01) was detected, while Prlr and Ghrh
      had a highly significant association (p < or = 0.01) with CH50 only.

PMID- 18817299
TI  - Effect of porcine reproductive and respiratory syndrome virus on porcine alveolar
      macrophage function as determined using serial analysis of gene expression
      (SAGE).
AB  - Porcine reproductive and respiratory syndrome virus (PRRSV) is a major pathogen
      of swine worldwide and causes considerable economic loss. The main target of
      infection is the porcine alveolar macrophage (PAM). Infection of PAMs by PRRSV
      causes significant changes in their function by mechanisms that are not
      understood. We have employed Serial Analysis of Gene Expression (SAGE) to examine
      the global expression of genes in PRRSV-infected PAMs. Total cellular RNAwas
      prepared from in vitro mock-infected and PRRSV strain VR-2332-infected PAMs at 0,
      6, 12, 16 and 24 hours after infection, and subjected to SAGE analysis to obtain
      > 100,000 tags per time point. These sequences were processed to account for
      sequencing error before generating tag:count lists. These lists were deposited
      into a modified Identitag database for mapping to porcine and PRRSV genes.
      Identified unique mRNAtags were analyzed for their identity and relative
      abundance. Examination of the SAGE data indicated that there were changes in gene
      expression occurring in the PRRSV-infected PAMs over time post-infection. More
      than 400 unique tags with significantly altered expression levels were identified
      (p < 0.01 with Bonferroni correction). The validity and kinetics of expression of
      SAGE identified genes were evaluated using real-time RT-PCR.

PMID- 18817300
TI  - Immediate early responses of avian tracheal epithelial cells to infection with
      highly pathogenic avian influenza virus.
AB  - Highly pathogenic (HP) avian influenza viruses (AIV) present an ongoing threat to
      the world poultry industry. In order to develop new AIV control strategies it is
      necessary to understand the underlying mechanism of viral infection at mucosal
      respiratory sites. Chicken and duck tracheal epithelial cells systems (TEC) were
      developed to study early host responses to AIV infection on TEC. Infection of 2
      week-old chickens and ducks with the highly pathogenic AIV H5N1 Ck/Hong
      Kong/220/97 and Egret/Hong Kong/757.2/02 viruses together with TEC early
      responses to infection suggest the induction of differential innate immune
      responses. Growth curves indicated that although chicken and ducks TEC supported
      viral replication and re-infection, the capacity of the two viruses to replicate
      was not equal. A 42K probes chicken microarray system used to characterize
      differences in gene expression between chicken tracheal epithelial cells infected
      with these two highly pathogenic AIV identified expression of virus-specific
      molecular markers. The existence of dissimilar patterns of host gene expression
      as early as six hours post infection suggests that the differential growth
      characteristics of the two highly pathogenic AIV in tracheal epithelial cells is
      preceded by distinct host responses.

PMID- 18817301
TI  - Porcine genome-wide gene expression in response to tetanus toxoid vaccine.
AB  - The very early in vivo response to immune stimuli was studied using tetanus
      toxoid as a model antigen known to induce Th1 and Th2 responses. Eighteen weaning
      piglets were vaccinated subcutaneously with tetanus toxoid. Leukocyte RNAs were
      isolated from samplings before and 2, 4, 8, and 24 hours after vaccination. After
      competitive hybridization of a 13297 porcine 70-mer oligo microarray (Qiagen
      Operon NRSP8), subsequent image analysis and normalization, the data was analysed
      using analyses of variance (ANOVA) to identify genes regulated due to vaccination
      (ANOVA, p < or = 0.05; corresponding to false discovery q < or = 0.12). Of 8240
      probes representing genes expressed in leukocytes, 1289 genes showed differential
      expression. Results were exemplarily confirmed by real-time PCR. Holistic
      expression data was clustered to six prominent groups of genes with similar
      changes in expression patterns using a k-means algorithm. To get more insight
      into functional and structural components and impact of the genes represented in
      each cluster, the EASE score was used to identify Gene Ontology functional
      categories. The results showed that in vivo significant changes of expression
      profiles of peripheral blood mononuclear cells (PBMCs) occurred very early after
      immune stimuli. These alterations concerned genes of pathways related to immune
      response as well as other metabolic and regulatory pathways including ATP/energy
      metabolism, transcription, structural molecule activity, biosynthesis, and
      metabolism. The analysis reveals new functional candidate genes for traits
      related to immune responsiveness and also provides new insight into the
      interaction of immune response, and metabolic and endocrine status. This will
      facilitate a better understanding of the relationship between immune and
      performance traits.

PMID- 18817302
TI  - Detection and confirmation of a major QTL affecting resistance to infectious
      pancreatic necrosis (IPN) in Atlantic salmon (Salmo salar).
AB  - Infectious pancreatic necrosis (IPN) is a viral disease currently presenting a
      major problem to the aquaculture of Atlantic salmon (Salmon salar), during both
      the freshwater and seawater stages of production. Genetic variation in resistance
      to IPN has previously been demonstrated and the purpose of this study was to
      determine whether this variation includes loci of major effect. The initial QTL
      detection methodology utilized the limited recombination seen in male salmon to
      detect QTL in ten large full-sib families, using a genome-wide scan of two to
      three markers per linkage group. QTL were then positioned by adding additional
      markers to the significant linkage groups in a female-based analysis. The most
      significant QTL was mapped to LG 21, and further confirmation of the LG 21 QTL is
      provided in an analysis of the QTL flanking markers in an additional nine full
      sib families from the same population. The size of QTL effect is such that the
      QTL flanking markers can be immediately applied in marker-assisted selection
      programmes to improve the resistance of salmon populations to IPN, thus reducing
      mortality due to the disease.

PMID- 18817303
TI  - Identifying genes for intestinal nematode resistance using transcriptional
      profiling.
AB  - Gene expression was compared between resistant and susceptible Perendale lambs
      that had either never been exposed to gastrointestinal nematode challenge (had a
      naive immune system with respect to parasites) or had been naturally challenged
      on pasture with nematodes. Only a small number of genes were differentially
      expressed between the naive resistant and susceptible animals, but many genes
      were differentially expressed between the resistant and susceptible challenged
      animals. The differentially expressed genes were involved in a variety of
      biological processes, most notably the immune response, the stress response and
      gene regulation via chromatin remodelling. The transcriptional profiling
      experiments also detected gene expression differences in the Ovar-DQA1 gene
      between resistant and susceptible challenged animals. A null allele of this gene
      was demonstrated to be associated with susceptibility to gastrointestinal
      parasites in some, but not all populations. This allele is not thought to be
      causal for susceptibility.

PMID- 18817304
TI  - High resolution, advanced intercross mapping of host resistance to Salmonella
      colonization.
AB  - Availability of a dense single-nucleotide polymorphism (SNP) map in chickens has
      allowed for whole-genome QTL mapping for disease resistance. In this study, two
      F8 advanced intercross lines of broiler by Fayoumi and broiler by Leghorn
      chickens, and a dense, genome-wide SNP panel were used to map genomic regions
      associated with host resistance to bacterial colonisation. One week after
      inoculation of day-old chicks with Salmonella enteritidis (SE), caecum and spleen
      tissues were collected to quantitate the bacterial load. Of 2733 genotyped SNPs,
      875 were homozygous and the remaining SNPs with a minor allele frequency of > 0.2
      were individually tested for association with SE burden by utilising a Chi-square
      log-likelihood test between models with and without SNP genotype. Using a Q-value
      of 25%, calculated utilising 1207 SNPs with Chi-square P-Value < 1.0 to control
      for false discovery, 21 SNPs identifying 19 genes were significantly associated
      with SE bacterial levels. Ten genes were in pathways associated with immune
      response to Salmonella (toll-like receptor signaling, apoptosis, and MAPK
      signaling), further supporting their involvement in host resistance pathways. In
      addition to identifying new candidate genes for bacterial resistance, the trait
      associated SNPs may be useful in marker assisted selection programmes for disease
      resistance.

PMID- 18817305
TI  - Predicting genetic merit for mastitis and fertility in dairy cattle using genome
      wide selection and high density SNP screens.
AB  - Two novel methods for genome wide selection (GWS) were examined for predicting
      the genetic merit of animals using SNP information alone. A panel of 1,546 dairy
      bulls with reliable EBVs was genotyped for 15,380 SNPs that spanned the whole
      bovine genome. Two complexity reduction methods were used, partial least squares
      (PLS) and regression using a genetic algorithm (GAR), to find optimal solutions
      of EBVs against SNP information. Extensive internal cross-validation was used
      tofind the best predictive models followed by external validation (without direct
      use of the pedigree or SNP location). Both PLS and GAR provided both accurate fit
      to the training data set for somatic cell count (SCC) (max r = 0.83) and
      fertility (max r = 0.88) and showed an accuracy of prediction of r = 0.47 for
      SCC, and r = 0.72 for fertility. This is the first empirical demonstration that
      genome wide selection can account for a very high proportion of additive genetic
      variation in fitness traits whilst exploiting only a small percentage of
      available SNP information, without use of pedigree or QTL mapping. PLS was
      computationally more efficient than GAR.

PMID- 18817306
TI  - On the search for markers of tick resistance in bovines.
AB  - Genetic differences in susceptibility to ticks (Rhipicephalus (Boophilus)
      microplus) are considerable in bovines. Here, mapping, association and gene
      expression approaches were employed to further advance our understanding of the
      molecular basis of tick resistance. A B. taurus x B. indicus F2 population was
      developed by Embrapa and 382 individuals were measured for parasitic load.
      Scanning of all chromosomes is in progress. Quantitative trait loci (QTL) for
      tick load were mapped to chromosomes 4, 5, 7, 10, 14, 18 and 23 out of the 20
      chromosomes scanned and were dependent on the season in which the phenotype was
      scored. In the candidate gene approach, females from the genetic groups Nelore
      (NE--184), Canchim x Nelore (CN--153), Aberdeen Angus x Nelore (AN--123) and
      Simmental x Nelore (SN--120) were evaluated under natural infestation.
      Microsatellite markers close to the genes for interleukin 2 (IL2), interleukin 4
      (IL4) and interferon gamma (IFNG) were analysed. Tick counts were associated with
      the marker for interleukin 4 (P < 0.05) in three genetic groups. Differences in
      cytokine mRNA levels of naive versus infested Nelore calves as well as between
      resistant versus susceptible cows from NE, CN and AN genetic groups were also
      investigated. Comparison of cytokines from infested and naive animals showed
      downregulation of IL2. When resistant cows were compared to susceptible animals,
      IL8 was downregulated. These results reinforce the multiloci nature of tick
      resistance and the need to consider QTL and environment interactions.

PMID- 18817307
TI  - Detection of germline and somatic copy number variations in cattle.
AB  - As a complement to the Bovine HapMap Consortium project, we initiated a
      systematic study of the copy numbervariation (CNV) within the same cattle
      population using array comparative genomic hybridization (array CGH).
      Oligonucleotide CGH arrays were designed and fabricated to cover all chromosomes
      with an average interval of 6 kb using the latest bovine genome assembly. In the
      initial screening, three Holstein bulls were selected to represent major paternal
      lineages of the Holstein breed with some maternal linkages between these lines.
      Dual-label hybridizations were performed using either Hereford L1 Dominette 01449
      or L1 Domino 99375 as reference. The CNVs were represented by gains and losses of
      normalized fluorescence intensities relative to the reference. The data presented
      here, for the first time, demonstrated that significant amounts of germline and
      fewer somatic CNVs exist in cattle, that many CNVs are common both across diverse
      cattle breeds and among individuals within a breed, and that array CGH is an
      effective tool to systematically detect bovine CNV. Selected CNVs have been
      confirmed by independent methods using real-time (RT) PCR. The strategy used in
      this study, based on genome higher-orderarchitecture variation, is a powerful
      approach to generating resources for the identification of novel genomic
      variation and candidate genes for economically important traits.

PMID- 18817308
TI  - Dynamic differential regulation of innate immune transcripts during the infection
      of alveolar macrophages by the porcine reproductive and respiratory syndrome
      virus.
AB  - Porcine reproductive and respiratory syndrome virus (PRRSV), an arterivirus, is
      the etiologic agent of an infectious disease of that name, characterized by
      respiratory disorders, abortion in pregnant sows and high mortality in piglets,
      resulting in significant economic losses in the pig industry worldwide. In order
      to identify whether genetic differences in PRRSV response may exist in pigs,
      alveolar macrophages were used to assess the progression of the type-I interferon
      (IFN) transcript response in porcine alveolar macrophages infected by PRRSV. Our
      results suggest that a dynamic differential regulation of the type-I IFN and
      chemokine transcripts may operate during the first hours of infection with and
      entry of the virus in alveolar macrophages, and provide a compelling mechanism
      for the establishment of PRRSV replication in susceptible cells.

PMID- 18817309
TI  - Identification of polymorphisms in bovine TLR2 and CARD15,associations between
      CARD15 polymorphisms and milk somatic cell score in Canadian Holsteins, and
      functional relevance of SNP c.3020A>T.
AB  - Toll-like receptor-2 (TLR2) and caspase recruitmentdomain 15 (CARD15) are
      important pattern recognition receptors that play a role in the initiation of the
      inflammatory and subsequent immune response. They have been previously identified
      as susceptibility loci for inflammatory bowel diseases in humans and are,
      therefore, suitable candidate genes for inflammatory disease resistance in
      cattle. The objective of this study was to identify single nucleotide
      polymorphisms (SNPs) in the bovine TLR2 and CARD15 and evaluate the association
      of these SNPs with health and production traits in a population of Canadian
      Holstein bulls. A selective DNA pool was constructed based on the estimated
      breeding values (EBVs) for somatic cell score (SCS). Gene segments were amplified
      from this pool in PCR reactions and the amplicons sequenced to reveal
      polymorphisms. A total of four SNPs, including one in intron 10 (c.2886-14A>G)
      and three in exon 12 (c.3020A>T, c.4500A>C and c.4950C>T)were identified in
      CARD15; nonewere identified in TLR2. Canadian Holstein bulls (n=338) were
      genotyped and haplotypes were reconstructed. Two SNPs, c.3020A>T and c.4500A>C,
      were associated with EBVs for health and production traits. The SNP, c.3020A>T
      for example, was associated with SCS EBVs (p = 0.0097) with an allele
      substitution effect of 0.07 score. When compared to the most frequent haplotype
      Hap12(AC), Hap22(TC) was associated with increased milk (p < 0.0001) and protein
      (p = 0.0007) yield EBVs, and hap21(TA) was significantly associated with
      increased SCS EBV (p = 0.0120). All significant comparison-wise associations
      retained significance at 8% experimental-wise level by permutation test. The role
      of SNP c.3020A>T in MDP induced IL-1beta expression was investigated by real-time
      quantitative reverse transcription-PCR (real-time quantitative RT-PCR). The
      induction of IL-1beta by MDP was highly variable between individuals, and no
      association was observed between IL-1beta expression and SNP c.3020A>T genotypes.
      In summary, the association study indicates that SNP c.3020A>T might play a role
      in the host response against mastitis; however, it is not the sole determinant of
      MDP induced IL-1beta expression in blood leukocytes. Further detailed studies are
      needed to understand the functional implications of SNP c.3020A>T.

PMID- 18817310
TI  - Associations between polymorphisms in the porcine haptoglobin gene and baseline
      levels of serum haptoglobin.
AB  - Haptoglobin (Hp) is an acute phase protein that is a marker in blood for clinical
      and subclinical disease in the pig. The aim of this study was to identify single
      nucleotide polymorphisms (SNPs) in the Hp gene and analyse their influence on
      baseline serum levels. DNA samples and serum were collected from 345 boars. Of 13
      SNPs identified, 5 were genotyped using PCR-RFLP and Pyrosequencing. Serum Hp
      levels were measured using a biochemical assay. A general linear model was fitted
      with line and genotype as fixed effects. In addition, linkage disequilibrium (LD)
      was estimated between the 5 SNPs using r-square and D prime. Serum Hp
      concentrations in the population showed a skewed distribution with a mean of 0.34
      g/L (range 0-2.65 g/L). Three SNPs were found to be associated with baseline Hp
      levels (p-value = 0.0093, 0.0051 and 0.0094). These 3 SNPs were also found to be
      in high LD with each other. This is the first study to find associations between
      polymorphisms in the porcine Hp gene and baseline Hp serum levels. The results
      have implications for breeding for resistance to infection.

PMID- 18817311
TI  - Single nucleotide polymorphism (SNP) in prion protein gene (PRNP) exon-3 in Gaddi
      sheep.
AB  - Nine PCR-SSCP conformations in PRNPthe exon-3 genomic DNA segment covering codons
      136, 154 and 171 were observed. DNA sequences revealed 9 unique variants
      (DQ885789-DQ885796). At codon 171 of exon-3, two alleles, Q and R, had a
      frequency of 0.336 and 0.664, respectively. Genotypes QQ, QR and RR were observed
      in 25.86, 15.51 and 58.62% of animals, respectively, showing deviation from Hardy
      Weinberg equilibrium. At codon 154, all genotypes were RR. At codon 136 AA, AV
      and W genotypes were 86.21, 10.34 and 3.44%, respectively, and frequencies of the
      alanine (A) and valine (V) alleles were 0.914 and 0.086, respectively, where the
      W genotype had lower frequency than expected. Polymorphisms were also observed at
      codons 137, 143 and 173 of exon-3.

PMID- 18817312
TI  - Delayed-type hypersensitivity response to KLH in F2 and backcrosses of two immune
      selected chicken lines: effect of immunisation and selection.
AB  - Cell-mediated immune response to keyhole limpet hemocyanin (KLH) was studied in
      13 different progeny groups belonging to a second generation cross between two
      lines of White Leghorn previously selected for 10 generations for high antibody
      response to Newcastle disease vaccine (ND3) and high cell-mediated response to
      phytohemagglutinin (PHA) measured as wing web swelling. The cutaneous
      hypersensitivity response to KLH was assessed in KLH immunized and non-immunized
      birds. Wing thickness was measured at three time points: before the injection and
      4 and 24 hours after the injection. The effect of previous immunization and
      genetic background was assessed. While no differences were present between
      progeny types or to a randomly bred control line at any of the three time points,
      significant differences were present between immunized and not immunized birds 24
      hours after challenge. Results demonstrate that KLH immunized birds perform
      better and that the previous selection and crossbreeding scheme has not
      influenced the intensity of the skin swelling response to KLH. Apparently,
      neither selection for antibody responsiveness to ND3 nor selection for enhanced
      responsiveness to a T cell mitogen affected delayed-type hypersensitivity (DTH)
      to the Th 2 antigen KLH. These results may serve to facilitate further selection
      based on independent immune parameters.

PMID- 18817313
TI  - Molecular genotype investigation of the Gallus gallus major histocompatibility
      complex.
AB  - The association between genetic markers and serological major histocompatibility
      complex (MHC) definition was studied in experimental White Leghorn lines selected
      for different immune traits. Different markers, three variable number tandem
      repeats (VNTRs) and 10 single nucleotide polymorphisms (SNPs), distributed along
      the MHC sequence were genotyped. Correlation between VNTR marker alleles and
      serology was studied in more than 800 animals and correspondence between SNP
      haplotypes and allele size was defined. A complete table of correspondence
      between VNTR allele sizes, SNP genotypes and serology was then drawn. This
      research shows that integrating new molecular tools can definitely help in MHC
      haplotype characterization and that, since the chicken MHC locus has been
      associated with disease resistance, these tools are becoming more and more needed
      for disease resistance and immunogenomics studies.

PMID- 18817314
TI  - Verification of chromosomal regions affecting the innate immunity in pigs using
      linkage mapping.
AB  - Understanding the genetic control of innate immunity in pigswould offerthe
      opportunity to utilize natural variation and improve selective breeding
      programmes. As part of our porcine genome scan to identify quantitative trait
      loci (QTL) we examined immune response traits in a Duroc x Berlin miniature pig
      resource family (DUMI). Complement activity via classical (CH50) and alternative
      (AH50) pathways, antibody response to Mycoplasma hyopneumoniae (Mh), tetanus
      toxoid (TET) and PRRS virus (PRRSV), the complement component (C3c), and
      Haptoglobin serum concentration (HP) were used as phenotypes for linkage mapping.
      A total of 220 backcross animals were used for the QTL analysis. Blood was
      collected six times from each animal prior to and after vaccinations against
      Mycoplasma hyopneumoniae, tetanus toxoid and PRRS, respectively. Seventy-four
      microsatellites from 18 autosomes were used for QTL mapping. The analyses were
      performed treating the measurements of phenotypes at different time points as
      single traits. Forty-two significant and 24 highly significant QTL were detected,
      using the program QTL Express, for all immune traits using the single traits.
      Most QTL were detected on SSC3, SSC16, and SSC18. No significant F-value
      corresponded to data for SSC12 and SSC13.

PMID- 18817315
TI  - IGF2/Mboll polymorphism in Gir and Nelore cattle.
AB  - The imprinted gene insulin-like growth factor 2 (IGF2) carries out important
      functions in the development of placental mammals, during the embryonic and fetal
      stages and is located on bovine chromosome 29. The main aim of this study was to
      verify the occurrence of a polymorphism (C/T transversion) in exon 6 of the IGF2
      gene in Gir and Nelore cattle, Zebu breeds of great economic importance in Brazil
      for dairy and beef production, respectively. A 193 bp fragment of bovine IGF2
      exon 6 was amplified by PCR with specific primers for this region and digested
      with Mboll enzyme to analyze the polymorphic segment. In a total of 39 Gir
      animals (29 females and 10 males), the estimated frequencies of the C and T
      alleles were 0.42 and 0.58, respectively. The genotypic frequencies were 0.10 for
      CC, 0.26 for TT and 0.64 for CT. For 28 Nelore animals (17 females and 11 males),
      the estimated frequencies of the C and T alleles were 0.43 and 0.57,
      respectively. The genotypic frequencies were 0.18 for CC, 0.32 for TT, and 0.50
      for CT. This is the first report of the occurrence of this polymorphism in these
      breeds. The polymorphic site can be a regulatory motif with functional
      significance to gene regulation of the IGF2 gene. This polymorphism could be used
      to investigate the allele-specific expression of the IGF2 gene, its epigenetic
      status, and its role in developmental, growth and reproductive traits.

PMID- 18817316
TI  - A systematic, data-driven approach to the combined analysis of microarray and QTL
      data.
AB  - High-throughputtechnologies inevitably produce vast quantities of data. This
      presents challenges in terms of developing effective analysis methods,
      particularly where the analysis involves combining data derived from different
      experimental technologies. In this investigation, a systematic approach was
      applied to combine microarray gene expression data, quantitative trait loci (QTL)
      data and pathway analysis resources in order to identify functional candidate
      genes underlying tolerance to Trypanosoma congolense infection in cattle. We
      automated much of the analysis using Taverna workflows previously developed for
      the study of trypanotolerance in the mouse model. Pathways represented by genes
      within the QTL regions were identified, and this list was subsequently ranked
      according to which pathways were over-represented in the set of genes that were
      differentially expressed (over time or between tolerant N'dama and susceptible
      Boran breeds) at various timepoints after T. congolense infection. The genes
      within the QTLthat played a role in the highest ranked pathways were flagged as
      good targets for further investigation and experimental confirmation.

PMID- 18817317
TI  - Evaluation of MAFbx expression as a marker for congenital splay leg in piglets.
AB  - Splay leg is a hereditary syndrome observed in highly varying frequency in
      newborn piglets. Although the phenotype indicates a muscular weakness, the
      etiology is still poorly understood. Only recently, the gene expression of muscle
      atrophy F-box (MAFbx; FBXO32) was proposed as being of diagnostic value for splay
      leg in piglet. In this study, total RNA from three healthy and three affected
      male piglets was isolated. Samples were collected from M. gracilis, Mm.
      adductores, and M. sartorius. Further samples were taken for histological and
      biochemical analyses. Expression of MAFbx was analysed by real-time RT-PCR and
      with the GeneChip" Porcine Genome Array (Affymetrix). No significant differences
      (p>0.05) were observed in relative MAFbx expression, either between the three
      muscles or between splay leg and healthy piglets for each muscle. The expression
      of further atrophy-related genes was unchanged, indicating that splay leg is not
      characterized by general muscular atrophy in the affected hind limbs. This is
      supported by histological and biochemical data that does not demonstrate signs of
      atrophy in splay leg muscles. We conclude that the diagnostic value of MAFbx
      expression for congenital splay leg in piglets is doubtful and that the disease
      is characterized by heterogeneous alterations in skeletal muscle.

PMID- 18817318
TI  - Organization of D(H)-gene locus is distinct in cattle.
AB  - Some cattle antibodies are amongst the largest known to exist, in a species where
      CDR3 of the heavy-chain variable region (CDR3H) is of exceptional size as it may
      extend up to 61 amino acids. The origin of such an exceptionally long CDR3H in
      cattle antibodies is not yet understood. For these reasons, we have completely
      characterized DH gene locus in a Holstein cow. In contrast to other species, such
      as mice and humans, the DH gene locus in cattle, extending over 68 kb, is
      organized in subclusters comprising two to four DH gene segments. Analysis of DH
      genes reveals the presence of characteristic repetitive GGT and TAT codons. No
      evidence for a DH gene segment longer than 148 base pairs has been noted.
      Therefore, mechanistic factors contribute significantly to CDR3H size generation.
      Such comparative genomics perspectives of bovine D gene loci have revealed the
      complexity of evolution, across animal phyla, of functional significance in the
      generation of antibody diversity.

PMID- 18817319
TI  - Differential gene expression of high and low immune responder Canadian Holstein
      dairy cows.
AB  - Infectious diseases are an important cause of economic loss in the agri-food
      business. This study investigates indicators of bovine high (HR) and low (LR)
      immune response and their associated patterns of gene expression. Holstein cows
      were immunized to induce antibody (AMIR) and cell-mediated (CMIR) immune
      responses. Based on the results of enzyme-linked immunosorbent assay (ELISA) and
      delayed-type hypersensitivity (DTH), cows were ranked as HR, LR or average (AR)
      immune responders. For microarray analysis, phenotypic HR and LR status in both
      groups was confirmed and total RNA from blood mononuclear cells (BMCs) was
      obtained. RNA from a pool of AR cows was used as a common reference for
      hybridization to an in-house cDNAmicroarray. Results of microarray analysis
      showed transcriptional differences in several immune-related genes between the HR
      and LR groups. Genes identified as differentially expressed include transcription
      factors, cytokines, MHC, and TCR-related genes. These results can aid in the
      establishmentof selection programmes based on broad-based disease resistance,
      aimed at improving general health in cattle herds.

PMID- 18817320
TI  - CDNA microarray analysis of gene expression patterns in blood mononuclear cells
      of SLA-DRB1-defined Yorkshire pigs.
AB  - Three lines of commercialYorkshire pigs with defined SLA-DRB1 alleles were
      developed at the University of Guelph for xenotransplantation and immune response
      studies. Two of the SLA-DRB1 alleles have been previously reported (SLA-DRB1*0502
      and *0701), whereas the third one is a new allele. The influence of defined SLA
      DRB1 alleles on transcriptional patterns of immune-related genes in blood
      mononuclear cells (BMCs) of pigs was explored using cDNA microarray. Microarray
      analysis showed significant differential expression of inflammatory genes in
      association with the various SLA-DRB1 alleles. A better understanding of the
      association between SLA genotypes and gene activity can increase the knowledge of
      the function of these molecules, as well as define new strategies to control
      animal health and optimize animal production.

PMID- 18817321
TI  - Opportunities for collaborative phenotyping for disease resistance traits in a
      large beef cattle resource population.
AB  - The Germplasm Evaluation (GPE) Project at the US Meat Animal Research Center
      (USMARC) is planned to produce about 3,000 calves per year in support of the
      following objectives: identification and validation of genetic polymorphisms
      related to economically relevant traits (ERT), estimation of breed and heterosis
      effects among 16 breeds for ERT, and estimation of genetic correlations among ERT
      and physiological indicator traits (PIT). Opportunities exist for collaboration
      in the development and collection of PIT phenotypes for disease resistance. Other
      areas of potential collaboration include detailed diagnosis (identification of
      disease causing organisms, etc.) of treated animals, collaborative development of
      epidemiological statistical models that would extract more information from the
      records of diagnoses and treatments, or pharmacogenetics. Concentrating a variety
      of different phenotypes and research approaches on the same population makes each
      component much more valuable than it would be individually.

PMID- 18817322
TI  - Functional characterization of a single nucleotide polymorphism in the 5' UTR
      region of the bovine toll-like receptor 4 gene.
AB  - Toll-like receptor 4 (TLR4) is the key receptor for the LPS component of Gram
      negative bacteria. We have identified a SNP within the 5' UTR region of the
      bovine TLR4 gene at position 226 (c.-226C>G) relative to start codon, which was
      found to be associated with health related traits in the Canadian Holstein
      population. TLR4 gene expression was measured over time intervals in samples
      collected from 18 cows (6 cows in each genotype) challenged in vitro with LPS (20
      ng/ml) to determine if this SNP alters the gene expression. TLR4 gene expression
      was highest 6 h post LPS challenge, and cows with the GG genotype exhibited
      significantly higher expression compared to other genotypes. This was further
      validated by a dual luciferase reporter gene assay in which sequential
      progressive constructs were cloned into the pGL3 basic vector and transfected
      into bovine Mac-T cells. The reporter construct containing most of the 5' UTR (
      456G) exhibited significantly higher luciferase activity compared to-456C,
      however, further inclusion of 5' upstream sequence showed a reversal phenomenon
      where the -913C construct exhibited significantly higher activity compared to 
      913G. These results indicate that the c.-226C>G SNP affects the expression of
      TLR4, suggesting that this SNP might be influencing the binding and interaction
      of transcription factors regulating gene expression.

PMID- 18817323
TI  - SNP discovery in genes affecting leg health traits in pigs.
AB  - Sow reproductive life is influenced by lameness issues. It has been reported that
      up to 44 percent of sows have locomotive problems. To date, few genome scans or
      association studies have been conducted to look at genes controlling lameness and
      other gait traits. In addition to health problems associated with leg and bone
      disorders, the pig has been suggested to be a good model for human bone
      disorders. Hence, the present study examined 134 porcine genes affecting skeletal
      development, mineral metabolism and other candidate genes for single nucleotide
      polymorphism (SNP) discovery. Atotal of over 370 SNPs have been identified to
      date and are being mapped. These SNPs are also being investigated for their
      associations with gait and locomotion problems in approximately 2,000 commercial
      pigs scored for various leg and locomotion traits. The association analysis of 22
      genes revealed that the genes CALCR, HDBP CALCA, MTHFR, OXTR, IHH, ANKH, LRCH1
      and OPN were significantly associated with leg and body conformation traits which
      affect the health and productivity of pigs.

PMID- 18817324
TI  - Mapping MHC genes in river buffalo.
AB  - The major histocompatibility complex (MHC) contains a set of genes necessary for
      antigen presentation in the immune system. This gene dense and polymorphic region
      of the mammalian genome is of considerable interest due to the role of MHC genes
      in immune function and animal health. Previous cytogenetic studies have indicated
      that the MHC in river buffalo resides on the short arm of chromosome 2 (BBU2). A
      5000-rad radiation hybrid mapping panel was recently generated to enable
      construction of a whole genome map of river buffalo. To this end, the aims of
      this project were to elucidate the general organization of the MHC on BBU2, and
      to compare gene order within this region to the MHC in cattle. PCR primers were
      selected from the bovine gene map and used with the BBURH5000 panel to map a set
      of ten MHC class II genes in river buffalo. Analysis indicates that these genes
      fall into two linkage groups, consistent with organization of the MHC in cattle.
      This comparison of buffalo and bovine MHC gene order provides the first insight
      into the organization of the MHC on river buffalo chromosome 2.

PMID- 18817325
TI  - Single nucleotide polymorphisms of interleukin-1 beta related genes and their
      associations with infection in the horse.
AB  - In previous work, we found significant associations of horse chromosome 15
      (ECA15) microsatellite markers HMSO1 and HTG06 with two horse infections,
      Rhodococcus equi and Lawsonia intracellularis, respectively. Interleukin-1 beta
      subunit and interleukin-1 receptor antagonist encoding genes (IL1B and IL1RN)
      could be considered as candidate genes underlying the associations reported.
      Therefore, we identified single nucleotide polymorphisms (SNPs) within three
      interleukin-1 beta functionally related genes: IL1B, IL1RN and Casp1 (interleukin
      1 beta converting enzyme/caspasel encoding gene). Using appropriate restriction
      fragment length polymorphism (PCR-RFLP) and/or single strand conformation
      polymorphism (PCR-SSCP) markers, their associations with the two infections by
      genotyping foals from the original study were tested. In addition, the physical
      localization of one of the two closely located genes, IL1RN, was re-assessed by
      fluorescence in-situ hybridization (FISH). A statistically significant
      association between an intronic SNP of the Casp1 gene with R. equi infection was
      found. The IL1RN gene was localized to 15q13-q14 in agreement with its originally
      reported physical position.

PMID- 18817326
TI  - An integrated approach of genetic resistance to Salmonella carrier state in
      fowls: from genetics to genomics and modelling.
AB  - Increasing resistance to acute Salmonellosis (that is, contamination level
      shortly after infection) is not sufficient to reduce the risk for consumers to be
      contaminated by Salmonella. Indeed, animals may remain contaminated at a low
      level for weeks or months. Increased resistance to the Salmonella carrier state,
      i.e., animals' ability to clear bacteria, is needed; it involves measuring
      bacterial contamination several weeks after inoculation with a low dose. To study
      such resistance traits, three convergent approaches were used. A quantitative
      trait loci (QTL) study was performed, taking advantage of inbred lines differing
      in resistance. Several QTLs controlling resistance at a younger age were
      identified and are currently being confirmed in a new cross before finer mapping,
      using advanced intercross lines. These inbred lines are also presently being
      compared using functional genomics. In parallel, a selection experiment for
      increased or decreased resistance at a younger and a later age was undertaken.
      Besides providing genetic models differing in their levels of resistance, it
      underlined the importance of the choice of selection criterion, whether marker
      assisted or not. Indeed, genes controlling resistance are strongly dependant on
      age; selecting for resistance at a younger age might result in increased
      susceptibility at an older age. Finally, the results of this experiment were used
      in a model of the intra-flock propagation of Salmonella. It showed that
      introducing a proportion of resistant animals within a flock of susceptible hens
      could dramatically change the evolution of contamination. Moreover, it
      demonstrated the magnitude of synergy between selection and vaccination, which
      should enhance the interest of increased resistance. The results show that
      selection for increased resistance to the Salmonella carrier state may be
      efficient, providing that the appropriate criteria of selection are used.

PMID- 18817327
TI  - Mapping the BDA20 gene to BTAX.
AB  - The lipocalin family is a large group of proteins that exhibits great structural
      and functional variation both within and among species, including a significant
      number of animal-derived aeroallergens, such as the bovine BDA20 (major cow
      dander allergen). This protein is classified as an occupational allergen causing
      asthma and other work-related allergic disorders among dairy farmers. Using a
      somatic cell panel the BDA20 gene was assigned to the bovine X chromosome (BTAX)
      with a significant concordant value of 97% to the previously mapped reference
      marker MAF45. A radiation hybrid (RH) mapping approach confirmed the assignment
      of BDA20 to BTAX. Two-point LOD scores showed that BDA20 is linked to XBM451 with
      a LOD score of 22.1 for a theta value of 0.03.

PMID- 18817328
TI  - Using integrative genomics to elucidate genetic resistance to Marek's disease in
      chickens.
AB  - While rearing birds in confinement and at high density are very successful
      practices for producing poultry meat and eggs, these conditions may promote the
      spread of infectious diseases. Consequently, the poultry industry places
      greatemphasis on disease control measures, primarily at the animal husbandry
      level. The field of genomics offers great promise to complement these current
      control measures by providing information on the molecular basis for disease,
      disease resistance, and vaccinal immunity. This briefly summarizes some of our
      efforts to apply several genomic and functional genomics approaches to identify
      genes and pathways that confer genetic resistance to Marek's disease (MD), a
      herpesvirus-induced T cell lymphoma of chickens. By utilizing the "top-down"
      approach of QTL to identify genomics regions, and integrating it with "bottom-up"
      approaches of transcript profiling and Marek's disease virus (MDV)-chicken
      protein-protein interactions, three genes that confer resistance to MD are
      revealed, plus a number of other positional candidate genes of high confidence.
      These genes can be further evaluated in poultry breeding programmes to determine
      if they confer genetic resistance to MD. This integrative genomics strategy can
      be applied to other infectious diseases. The impact of the genome sequence and
      other technological advancements are also discussed.

PMID- 18817329
TI  - Machine learning classification procedure for selecting SNPs in genomic
      selection: application to early mortality in broilers.
AB  - In genome-wide association studies using single nucleotide polymorphisms (SNPs),
      typically thousands of SNPs are genotyped, whereas the number of phenotypes for
      which there is genomic information may be smaller. Atwo-step SNP (feature)
      selection method was developed, which consisted of filtering (using information
      gain), and wrapping (using naive Bayesian classification). This was based on
      discretization of the continuous phenotypic values. The method was applied to
      chick early mortality rates (0-14 days of age) on progeny from 201 sires in a
      commercial broiler line, with the goal of identifying SNPs (over 5000) related to
      progeny mortality. Sires were clustered into two groups, low and high, according
      to two arbitrarily chosen mortality rate thresholds. By varying these thresholds,
      11 different "case-control" samples were formed, and the SNP selection procedure
      was applied to each sample. To compare the 11 sets of chosen SNPs, predicted
      residual sum of squares (PRESS)from a linear model was used. Naive Bayesian
      classification accuracy was improved over the case without feature selection
      (from 50% to 90%). Seventeen SNPs in the best case-control group (with smallest
      PRESS) accounted for 31% of the variance among sire family mortality rates.

PMID- 18817330
TI  - The use of RNAi and transgenics to develop viral disease resistant livestock.
AB  - The possibility of genetically engineering poultry to make them resistant to
      avian influenza is attracting attention and has now become a real possibility
      with improved methods for genetic modification and the emergence of RNAi as an
      antiviral strategy. In order to test this possibility, we have generated
      transgenic mice that express RNAi molecules targeting a conserved region of the
      influenza A NP gene and are testing these mice for resistance to influenza
      infection. Transgenes were initially developed that express short hairpin RNAs
      (shRNAs) targeting multiple influenza A viral genes. The shRNAs were tested for
      inhibition of H1N1 PR8 virus in vitro. Two potent shRNAs that target the NP and
      PA genes were chosen for lentiviral mediated generation of transgenic mice.
      Transgenic founders for the NP shRNA construct and also a negative control
      shRNAtargeting EGFP were generated. The constitutive expression of the shRNA
      molecules in a range of tissue types including lung, was confirmed and so far
      stable transmission of the RNAi transgenes from the F0 to F3 generation has been
      observed. Resistance to influenza infection in these transgenic mice is now being
      confirmed.

PMID- 18817331
TI  - The use of high density genotyping in animal health.
AB  - The sequencing of genomes, such as that of the cow, has led to the discovery of
      thousands of single nucleotide polymorphisms (SNPs). By combining this knowledge
      with new methods that can genotype thousands of SNPs efficiently, it has become
      possible to carry out genome-wide association studies in domestic animals to map
      genes for complex traits, including disease resistance, using the linkage
      disequilibrium between the SNPs and the unknown genes affecting the trait of
      interest. Although experiments using 10,000 SNPs and 384 animals have found many
      significant associations, power calculations suggest that we need >50,000 SNPs
      and >1000 animals to map genes explaining most of the genetic variance for
      complex traits. Such experiments are now underway and the results will have two
      applications. Firstly, they will lead to panels of SNPs that can be used to
      accurately select animals with high breeding value for desired traits leading to
      a great increase in the rate of genetic improvement. Secondly, they will form the
      first step in identifying the genes and mutations that cause variation in complex
      traits. A collaborative approach to achieving this second goal is proposed.

PMID- 18817332
TI  - Epigenetic regulation of genomes: nutrient-specific modulation of genetic
      networks in bovine cells.
AB  - The modern version of epigenetics includes the molecular mechanisms that
      influence the phenotypic outcome of a gene or genome, in absence of changes to
      the underlying DNA sequence. A host of genomic interrelationships with the diet
      evidently exist. The broad topic of nutrigenomics is defined as the interaction
      between nutrition and an individual's genome. Ruminant species have evolved to
      metabolize the short-chain volatile fatty acids (VFAs, acetate, propionate, and
      butyrate) to fulfill up to 70% of their nutrient energy requirements. The
      potential biological roles of VFAs were investigated using the established Madin
      Darby bovine kidney epithelial cell line. Butyrate induces cell cycle arrest and
      apoptosis in bovine cells. Gene expression profiling indicated that butyrate
      induces many significant changes in the expression of genes associated with
      regulatory pathways that are critical to cell growth, immune response and signal
      transduction. Functional category and pathway analyses of the microarray data
      revealed that several canonical pathways (the cell cycle G2/M DNA damage
      checkpoint and G1/S checkpoint regulation; pyrimidine metabolism; and purine
      metabolism insulin-like growth factor axis components) were significantly
      affected.

PMID- 18817333
TI  - Diagnostic markers for diseases: SELDI-TOF profiling of pig sera for PRRS.
AB  - Porcine reproductive and respiratory syndrome (PRRS) is a highly infectious viral
      disease causing severe losses to the pig industry. Most weaning piglets are
      likely to be exposed to the infection and show at least asymptomatic PRRS viremia
      strongly related to productive performance. The aims of this study were to set up
      experimental conditions for pig sera proteomic profiling and to identify
      biomarkers that differentiate weaning asymptomatic piglets positive to PRRS
      viremia from negative controls (PCR tested) with potential predictive value for
      the subsequent occurrence of clinical PRRS. Protein profiles were generated by
      SELDI-TOF MS using the Bio-Rad Chips WCX, IMAC30 and H50. The discovery phase
      revealed that a consistent number of highly significant protein peaks can be
      detected by the WCX and IMAC30 surfaces; however none of these peaks were
      statistically confirmed by the subsequent validation phase, highlighting that
      serum concentration of the contaminant and most abundant proteins is a crucial
      parameterfor SELDI-TOF MS studies. Current protocols are being furtheroptimized
      and adapted to pig sera to reduce the unfavourable effects of the most abundant
      proteins and to increase the number of potential detectable biomarkers.
      Furthermore, proteomic fingerprint profiling has been shown to be a promising
      diagnostic tool that, in the future, may be useful to provide also insights into
      the mechanisms of early viral infection in vivo.

PMID- 18817334
TI  - Animal genomics for animal health report: critical needs, problems to be solved,
      potential solutions, and a roadmap for moving forward.
AB  - The first International Symposium on Animal Genomics for Animal Health, held at
      the World Organisation for Animal Health (OIE) Headquarter, 23-25 October, 2007,
      Paris, France, assembled more than 250 participants representing research
      organizations from 26 countries. The symposium included a roundtable discussion
      on critical needs, challenges and opportunities, and a forward look at the
      potential applications of animal genomics in animal health research. The aim of
      the roundtable discussion was to foster a dialogue between scientists working at
      the cutting edge of animal genomics research and animal health scientists. In an
      effort to broaden the perspective of the roundtable discussion, the organizers
      set out four priority areas to advance the use of genome-enabled technologies in
      animal health research. Contributions were obtained through open discussions and
      a questionnaire distributed at the start of the symposium. This symposium report
      provides detailed summaries ofthe outcome ofthe roundtable discussion for each of
      the four priority areas. For each priority, the problems needing to be solved,
      according to the views of the participants, are identified, including potential
      solutions, recommendations, and lastly, concrete steps that could be taken to
      address these problems. This report serves as a roadmap to steer research
      priorities in animal genomics research.

PMID- 18817335
TI  - Animal genomics for animal health. Closing remarks.

PMID- 18817336
TI  - [Progress in the research of Sertoli cell cytoskeleton of the testis].
AB  - This article introduces the structure and function of the Sertoli cell
      cytoskeleton of the testis and the research progress in this aspect, focusing on
      the description of the function of vimentin, with some illustrations on the
      impact of physical and chemical factors on cytoskeleton, especially the
      structural changes of vimentin cell microfilament under simulated microgravity
      and space true microgravity. It for the first time proposes that the Sertoli cell
      cytoskeleton can be detected in semen, with a view to involving more researchers
      in further studies in this field.

PMID- 18817337
TI  - [Differential expression of ubiquitin C-terminal hydrolase L-1 in the rat testis
      following exposure to di-n-butyl phthalate in utero].
AB  - OBJECTIVE: To identify and analyze the differential expression of ubiquitin C
      terminal hydrolase L-1 (UCHL1) in the testis of rat offspring after maternal
      exposure to di-n-butyl phthalate (DBP). METHODS: Forty pregnant rats were
      randomly divided into two groups and given DBP by gastric intubation at the dose
      of 800 mg/(kg x d) or none from the 14-18th day of pregnancy. Testes were
      harvested from the fetal and neonatal rats of the normal and exposed groups
      respectively at GD19 and PND22. The expression of UCHL1 was detected and analyzed
      by Western blot and immunohistochemistry. RESULTS: The UCHL1 expression was 50%
      lower in the DBP-exposed group than in the normal controls on GD19 (P < 0.01),
      but showed no significant difference between the two groups on PND22 (P > 0.05).
      UCHL1 was mainly located in the cytoplasm and nuclei of spermatogonia, primary
      spermatocytes and sub-primary spermatocytes in the developmental phase of the
      testis. CONCLUSION: Exposure in utero to DBP affects the UCHL1 expression in
      testicular spermatogenic cells, disturbs the balance of the ubiquitin-proteasome
      system and consequently causes maldevelopment of the testis with thinner
      seminiferous tubules and reduced count of spermatogenic cells.

PMID- 18817338
TI  - [DNA damage induces BRCA1 distribution alteration in prostate cancer cell lines].
AB  - OBJECTIVE: To investigate the role of the tumor suppressor gene BRCA1 in response
      to DNA damage and to confirm that the function of the BRCA1 protein is regulated
      by a variety of mechanisms including transcriptional control, phosphorylation and
      protein-protein interaction. METHODS: With the human breast cell line MCF7 as the
      positive control, we determined the subcellular distribution of BRCA1 in the
      prostate cancer cell lines LNCaP, DU145 and PC3 by immunohistochemical staining
      and Western blotting analyses. RESULTS: BRCA1 was present in the prostate cancer
      cell lines LNCaP, DU145 and PC3. Ionizing radiation induced BRCA1 nuclear export,
      increasing from 14% to 40% in the cytoplasma (P < 0.01) and decreasing from 46%
      to 21% in the nuclei (P < 0.01). This DNA damage-induced BRCA1 nuclear export
      occurred only in the p53 wild-type but not in the p53 mutant cell line. The
      apoptosis rate of LNCaP cells was as high as 40% after nuclear export, with an
      obvious increase of cleaved caspase-3, which was correlated with BRCA1 nuclear
      cytoplasmic shuttling. CONCLUSION: Cytoplasmic relocalization of the BRCA1
      protein may be a mechanism whereby the BRCA1 function is regulated in response to
      DNA damage. Its induction of a higher rate of cell apoptosis indicates BRCA1 to
      be another good biomarker for the treatment of prostate cancer.

PMID- 18817339
TI  - [Dose and long-term effect of hIGF-1 injection for erectile dysfunction in aged
      rats].
AB  - OBJECTIVE: To investigate the best dose and the long-term effect of the human
      insulin-like growth factor-1 (hIGF-1) gene injection into the penis of aged rats.
      METHODS: Included in this study were 10 young (4 months old) and 40 aged (24
      months old) Sprague-Dawley male rats, the latter equally divided into a PBS
      control and a 10 microg, a 100 microg and a 1 000 microg hIGF-1 injection group.
      Electrical stimulation was conducted 4 and 8 weeks after hIGF-1 injection into
      the penile corpus cavernous of the rats to detect the intracavernous pressure
      (ICP) and mean arterial pressure (MAP). Dose - and time -associated therapeutic
      results were analyzed and the mRNA expression of hIGF-1 determined by RT - PCR.
      RESULTS: ICP, MAP and total ICP were significant decreased by electrical
      stimulation in the aged rats as compared with the young ones (P < 0.05),
      statistically increased in the three hIGF-1 dose groups in comparison with the
      PBS controls (P < 0.05), and showed no obvious difference between the young rats
      and the latter two dose groups at 4 and 8 weeks. Although less obvious effect was
      achieved in the 10 microg group than in the young rats, the therapeutic result
      was still of significance. The mRNA expression of the hIGF-1 gene was confirmed
      in all the hIGF-1 treated rats. CONCLUSION: The hIGF-1 therapy can improve
      erectile function in aged rats, 100 microg suffices for effective erection and
      the effect may last at least 8 weeks for a single dose.

PMID- 18817340
TI  - [Establishment of a long-term culture system for mouse spermatogonial stem cells
      in vitro].
AB  - OBJECTIVE: To establish a long-term proliferation culture system for mouse
      spermatogonial stem cells. METHODS: Testis tissues were obtained from 30 newborn
      male ICR mice on postnatal day 2-6. Testis cell suspension was collected by two
      step enzymatic digestion prior to culture. The dissociated cells were aliquoted
      into tissue culture plates and cultivated with a modified system composed of
      serum-free defined medium on mouse embryonic fibroblasts (MEF) feeders. Their
      proliferation was determined by the BrdU incorporation test and the cultured
      cells identified by alkaline phosphatase (AP) activity, immunofluorescence
      staining and RT-PCR assay. RESULTS: The cultures remained in a steady state and
      continued to generate germ cell colonies. The undifferentiated state was
      confirmed by strong positivity for AP activity, immunofluorescent staining of
      GFRalpha-1+ /Oct-4+ /VASA+ /SCP3- and GFRalpha-1+ /Oct-4+/SCP3- at the gene
      expression levels. CONCLUSION: Mouse spermatogonial stem cells could be expanded
      in our defined culture system and passaged steadily in vitro. The harvested cells
      remained in an undifferentiated state, which has provided a good platform for the
      study of spermatogenesis in vitro.

PMID- 18817341
TI  - [Nitric oxide synthetase and carbon monoxide decrease in the penile corpus
      cavernous of hyper homocysteine rats].
AB  - OBJECTIVE: To detect the levels of nitric oxide synthetase (NOS) and carbon
      monoxide (CO) in the penile corpus cavernous of adult male Wistar rats with high
      homocysteine (Hhcy) and to explore the relationship of NOS and CO levels with
      erectile dysfunction. METHODS: Twenty Wistar rats were equally and randomly
      divided into a control and an Hhcy group and fed on normal diet and normal diet
      with 3.0% methionine respectively. Four weeks later, the levels of NOS and CO in
      the penile corpus cavernous were detected by ultraviolet spectrophotometry and
      that of serum homocysteine by the cycle enzyme method. RESULTS: Compared with the
      control group, the levels of NOS and CO in the penile corpus cavernous were
      significantly lower in the Hhcy group, (6.45 +/- 1.12) nmol/(g x min) vs (10.77
      +/- 0.60) nmol/(g x min) and (10.60 +/- 0.92) micromol/L vs (13.36 +/- 0.44)
      micromol/L, while that of homocysteine was significantly higher, (22.32 +/- 1.65)
      micromol/L) vs (4.90 +/- 1.73) micromol/L. CONCLUSION: Four-week diet with
      methionine can cause Hhcy and significantly decreased levels of NOS and CO in the
      penile corpus cavernous in Wistar rats. Hhcy is an independent risk factor of
      erectile dysfunction.

PMID- 18817342
TI  - [Seminal plasma levocarnitine significantly correlated with semen quality].
AB  - OBJECTIVE: To investigate the relationship of seminal plasma levocarnitine with
      sperm concentration, vitality and motility. METHODS: Enrolled in this study were
      64 infertile men, who were divided according to the results of routine sperm
      tests into a normozoospermia (n = 12), an oligozoospermia (n = 16), an
      asthenozoospermia (n = 20) and an oligoasthenozoospermia group (n = 16). The
      level of seminal plasma levocarnitine was detected by LC-MS-MS, the concentration
      of seminal plasma testosterone measured by chemiluminescence immunoassay, the
      correlation of seminal plasma levocarnitine with sperm concentration, motility
      and vitality determined by bivariate correlation analysis with SPSS15.0, and so
      was the correlation between the carnitine and sperm concentration by partial
      correlation analysis with seminal plasma testosterone as a control variable to
      exclude the influence of testosterone. RESULTS: The concentrations of total
      seminal plasma levocarnitine, free seminal plasma levocarnitine and seminal
      plasma acetolevocarnitine were (91.33 +/- 40.49) mg/L, (40.89 +/- 24.13) mg/L and
      (50.44 +/- 21.90) mg/L; the Pearson coefficients of correlation of the
      levocarnitine level with sperm motility, vitality and concentration were 0.161 (P
      = 0.235), 0.114 (P = 0.370) and 0.637 (P < 0.001), those of free seminal
      carnitine with sperm motility and vitality were 0.325 (P = 0.024) and 0.316 (P =
      0.029), respectively, with the oligozoospermia group excluded, and that of
      partial correlation between the concentrations of seminal levocarnitine and sperm
      was 0.641 (P < 0.001). CONCLUSION: The level of seminal plasma levocarnitine is
      positively correlated with sperm motility and vitality, and more significantly
      with sperm concentration.

PMID- 18817343
TI  - [Radioactive damage induced by interstitial 125I seed implantation to rabbit
      urethra].
AB  - OBJECTIVE: To assess the radioactive damage induced by interstitial 125I seed
      implantation to the rabbit urethra. METHODS: We implanted 24 rabbits with 125I
      seeds 1.0 cm to the urethra at the radiation dose of 14.8 MBq (Group A), 29.6 MBq
      (Group B) and 44.4 MBq (Group C), while a non-radioactive seed was implanted near
      the urethra of the controls (Group D). Four weeks later, we detected the
      radiation-induced pathological and morphological changes in the urethra by H&E,
      light microscopy and electron microscopy. RESULTS: Four weeks after the
      implantation, no obvious histopathological and ultrastructural changes were
      observed in the urethral tissues of the experimental rabbits as compared with the
      control group. The scores on the radioactive damages to the urethra obtained by
      light microscopy were (2.20 +/- 0.18), (2.23 +/- 0.15), (2.27 +/- 0.10) and (2.10
      +/- 0.17) respectively in Group A, B, C and D, with no significant differences
      between the first three groups and the control (P > 0.05). And the scores on the
      FlaMeng semi- quantitative analysis of mitochondria in the experimental groups
      were (1.23 +/- 0.13), (1.34 +/- 0.25) and (1.41 +/- 0.30) respectively, not
      significantly different from (1.12 +/- 0.13) the control (P > 0. 05). CONCLUSION:
      The radioactive damage induced by 125I seeds to the urethra increases with the
      enhanced radiation dose. Intraoperative implantation of 125I seeds at the
      prescription dose has no obvious adverse effect on the rabbit urethra.

PMID- 18817344
TI  - [Preventive effect of daidzein on testosterone-induced prostatic hyperplasia in
      rats].
AB  - OBJECTIVE: To investigate the preventive effect of the phytoestrogen daidzein on
      prostatic hyperplasia induced by testosterone in rats. METHODS: Thirty-six male
      adult Sprague-Dawley rats were equally randomized into 6 groups: Group I and II
      (normal control and model, treated with 1 ml distilled water by oral gavage), and
      Group III-VI (low-, medium- and high-dose daidzein and positive control,
      respectively given daidzein at 2, 20 and 100 mg/kg and diethylstilbestrol at 0.1
      mg/kg once a day for 90 days). From the 91st day , Group III-VI were treated with
      subcutaneous injection of testosterone at 7.5 mg/kg/d for 10 days to induce
      prostatic hyperplasia. The wet weight and the index of the prostate were
      obtained, its morphological changes detected and the changes of ERalphaa and
      ERbeta expressions in the prostate observed by immunohistochemistry. RESULTS:
      Compared with the model group, the wet weight and the index of the prostate were
      significantly reduced in the 3 daidzein groups and the positive control group (P
      < 0.05 or P < 0.01). Medium- and high-dose daidzein induced a more obvious
      alleviation of prostate hyperplasia, characterized by thinner epithelia,
      decreased secretions in the glandular cavity and reduced interstitial tissues.
      The expression of ERalpha showed no significant difference between the model
      group and the other groups, while that of ERbeta was markedly decreased in the
      daidzein-treated groups as compared with the normal control or the model group.
      CONCLUSION: The phytoestrogen daidzein has some preventive effect on prostatic
      hyperplasia induced by testosterone in rats.

PMID- 18817345
TI  - [Matrine inhibits the proliferation of prostate cancer cells and the activity of
      androgen receptor].
AB  - OBJECTIVE: To study the inhibitory effect of matrine on the proliferation of the
      prostate cancer cell line LNCaP and the expression of the androgen receptor (AR).
      METHODS: LNCaP cells were treated with matrine at the concentration of 0.5, 1.0,
      1.5, 2.0 and 3.0 g/L for 12, 24 and 36 hours, the cell growth activity determined
      by MTT colorimetry and trypan blue staining at 36 hours, the cell cycle changes
      detected by flow cytometry and the expression of AR by Western blot at 24 hours.
      RESULTS: Matrine suppressed the in vitro growth of the androgen-sensitive
      prostate cancer cell line LNCaP in a time- and dose-dependent manner, blocked the
      cell cycles in the G2/M phase and decreased the expression of AR in the cell line
      in a dose-dependent manner (P < 0.01). CONCLUSION: Matrine can significantly
      inhibit the in vitro growth of NCaP cells by down-regulating the expression of AR
      and blocking cell cycles.

PMID- 18817346
TI  - [Correlation of the prognosis of chronic prostatitis/chronic pelvic pain syndrome
      with psychological and other factors: a Cox regression analysis].
AB  - OBJECTIVE: To establish the role of psychological factors in the etiology and
      symptomatology of chronic prostatitis / chronic pelvic pain syndrome (CP/CPPS),
      analyze the influence of the psychological obstacles and other relative factors
      on the prognosis of CP/CPPS by univariate and multivariate Cox regression
      analyses, and provide a scientific basis for psychotherapy of the problem.
      METHODS: A total of 291 CP/CPPS patients and 100 normal controls were
      investigated in age, education, occupation, character, disease course, NIH
      chronic prostatitis syndrome index (NIH-CPSI) and leukocyte count in EPS and by
      self-rating anxiety scale (SAS) and self-rating depression scale (SDS) to
      establish the psychological factors related with CP/CPPS. Then, all the CP/CPPS
      patients were treated with the same method and followed up for 6 weeks. Based on
      the therapeutic results, the influence of psychological and other relative
      factors on the prognosis of CP/CPPS was analyzed with univariate and multivariate
      Cox regression. RESULTS: All together 258 valid questionnaires were collected
      from the patients and 87 from the normal controls. Of the 258 CP/CPPS patients,
      the mean scores on SAS and SDS were 42.8 +/- 11.43 and 48.15 +/- 11.49
      respectively, both significantly higher than those of the controls (32.12 +/-
      9.68 and 35.12 +/- 10.81) (P < 0.01). The rates of anxiety, depression and
      anxiety and/or depression in the CP/CPPS group were 25.97, 21.71 and 34.50 %
      respectively, all significantly higher than in the control group (P < 0.01). The
      rate of introversion was significantly higher while that of extroversion
      significantly lower in the former than in the latter (P < 0.01). The total
      effectiveness rate of treatment was 70.54 % in the CP/CPPS patients. Univariate
      and multivariate analyses with Cox regression revealed that anxiety, depression
      and disease course were the definite factors that negatively affected the
      prognosis of CP/CPPS, while the other factors, such as age, CPSI, character and
      leukocyte count in EPS had no influence. CONCLUSION: Such psychological obstacles
      as anxiety and depression play an important role in the pathogenesis, development
      and prognosis of CP/CPPS. In the treatment of CP/ CPPS, importance should be
      attached to the patients'psychological status and proper psychological
      intervention is sometimes necessary.

PMID- 18817347
TI  - [Psychological factors and erectile function in men with refractory chronic
      prostatitis].
AB  - OBJECTIVE: To study the psychological factors and erectile function in patients
      with refractory chronic prostatitis. METHODS: We obtained and compared the scores
      on the NIH scales of chronic prostatitis symptoms, anxiety, depression and
      erectile function among 232 refractory and medical chronic prostatitis patients
      who had never received any psychotherapy. RESULTS: No significant differences
      were observed in the scores on chronic prostatitis symptoms between the
      refractory and the medical chronic prostatitis groups, while the scores on
      anxiety and depression were significantly higher and that on erectile function
      significantly lower in the refractory than in the medical group (P < 0.01), with
      a negative correlation between the scores on the former two items and that on the
      latter. CONCLUSION: Obvious psychological factors exist in patients with
      refractory chronic prostatitis, which may affect their erectile function.

PMID- 18817348
TI  - [An effective combined therapy for simple premature ejaculation].
AB  - OBJECTIVE: To observe the clinical effect of a combined therapy in the treatment
      of simple premature ejaculation. METHODS: A total number of 110 patients with
      simple premature ejaculation were divided into a control group (n = 50), given
      oral hydrochloric acid sertraline only, and a combined therapy group (n = 60),
      treated by oral administration of hydrochloric acid sertraline, local inunction
      of a traditional Chinese medicine and guidance in sexual psychology and
      knowledge. At the end of a 4-week treatment and 4 weeks after the drug
      withdrawal, the therapeutic effects were evaluated by ejaculation latency and
      satisfaction with sexual life. RESULTS: The total effectiveness rates at the end
      of the 4-week treatment were 91.6% and 76% in the combined therapy and the
      control groups, while those 4 weeks after the drug withdrawal were 68.3% and 42%
      respectively, both with significant differences in between (P < 0.05 and P <
      0.01). CONCLUSION: The combined therapy has a satisfactory clinical effect and
      stability in the treatment of simple premature ejaculation.

PMID- 18817349
TI  - [Holmium laser urethrotomy for male urethral stricture].
AB  - OBJECTIVE: To evaluate transurethral holmium laser incision, its safety and
      effect in the treatment of male urethral stricture. METHODS: Thirty-eight males
      with urethral stricture were treated by 1045 W holmium laser urethrotomy, 18 with
      the stricture length shorter than 1.0 cm, 9 between 1.0 cm and 1.5 cm, 7 longer
      than 1.5 cm , 4 with occlusive stricture and 6 companies with bladder calculus.
      The average peak urinary flow rate (Q(max)) was (5.6 +/- 2.3) ml/s. RESULTS:
      Successful surgery was achieved in 36 of the cases, with no complications and the
      average Q(max) increased to (17.5 +/- 3.4) ml/s. Two cases were converted to open
      surgery. Thirty-two cases were followed up for 3-18 months, of whom 4 received
      urethral dilation and 2 underwent a second holmium laser urethrotomy. CONCLUSION:
      Holmium laser urethrotomy is a safe, effective and minimally invasive therapeutic
      modality for male urethral stricture.

PMID- 18817350
TI  - [Vardenafil significantly alleviates erectile dysfunction in aged men with
      diabetes].
AB  - OBJECTIVE: To observe the efficacy and safety of vardenafil in the treatment of
      erectile dysfunction (ED) in aged men with diabetes mellitus (DM). METHODS: One
      hundred outpatients with diagnosed ED (40 diabetic and 60 non-diabetic) received
      vardenafil at the initial dose of 20 mg and sustained dose of 10 mg once a week
      for 8 weeks, and their erectile functions were evaluated by IIEF and EQS.
      RESULTS: The scores on IIEF and EQS in the diabetic ED group were 18.9 +/- 0.2
      and 25.1 +/- 1.4 after the vardenafil treatment, significantly higher than 8.1 +/
      0.5 and 9.1 +/- 1.3 before the treatment (P < 0.01), and the non-diabetic group
      scored 21.1 +/- 0.2 and 34.2 +/- 1.2 on IIEF and EQS after the treatment, as
      compared with the statistically lower scores of 10.1 +/- 0.3 and 10.1 +/- 1.7
      before it (P < 0.01). The total rate of effectiveness was 65% in the diabetic and
      73.30% in the non-diabetic group, with statistical differences (P < 0. 05).
      CONCLUSION: Vardenafil can significantly improve erectile function and is well
      tolerated in the aged males with diabetic ED.

PMID- 18817351
TI  - [Fatty acid synthase and prostate cancer].
AB  - The over expression of fatty acid synthase (FAS), a key enzyme in biosynthesis of
      fatty acid, can enhance enzyme activity and result in the malignant behavior,
      special material metabolism and energy metabolism of tumors. The expression of
      FAS is significantly higher in prostate cancer than in normal prostate tissues,
      which shows that FAS can be used as a marker in the early diagnosis of prostate
      cancer. The abnormally increased expression of FAS in prostate cancer may offer a
      new target for the drug treatment of the disease.

PMID- 18817352
TI  - [Influence of different types of prostatectomy on male sexual function].
AB  - With the approaching of the aged society, the number of patients with BPH and
      those with prostate cancer is increasing, particularly the latter. As the gold
      standard for the treatment of the two diseases, prostate surgery falls into
      various types, each with its own characteristics in postoperative recovery of
      sexual function. In the past few years, the traditional laparotomy procedure has
      been gradually replaced by the laparoscopic technique. Doctors and patients are
      not merely satisfied with the improvement of micturition function any longer;
      they are beginning to pay more attention to the pre- and post-operative sexual
      function. This paper gives an overview of the influence of various types of
      prostatectomy on male sexual function.

PMID- 18817353
TI  - [Multi-centered clinical trial of Fufang Xuanju capsule for oligoasthenospermia].
AB  - OBJECTIVE: To observe the efficacy of Fufang Xuanju Capsule in the treatment of
      oligoasthenospermia. METHODS: Using a multi-centered, open and self-controlled
      clinical trial, we treated 120 patients with oligoasthenospermia, with Fufang
      Xuanju Capsule for 12 weeks, and evaluated the efficacy of the capsule with sperm
      concentration and vitality (a + b) as the primary and the number of grade a
      sperm, sperm motility (a + b + c) and semen volume as the secondary therapeutic
      indexes. RESULTS: A total of 107 patients accomplished the clinical trial.
      Compared with pre-treatment, sperm density, vitality and motility were
      significantly improved after 4, 8 and 12 weeks of Fufang Xuanju treatment (P <
      0.01). At 12 weeks, sperm concentration was increased by 63.28%, with 73 cases
      (68.22%) restored to normal, sperm vitality by 63. 17%, with 39 (36.45%) restored
      to normal, sperm motility by 44.36%, with 77 (71.96%) restored to normal, and the
      semen volume by 18.13%. CONCLUSION: Fufang Xuanju Capsule can evidently improve
      the seminal quality of oligoasthenospermia patients.

PMID- 18817354
TI  - [Xiaojin Wan inhibits the expression of COX-2 in prostate tissues of prostatitis
      pain rats].
AB  - OBJECTIVE: To study the effect of Xiaojin Wan on the expression of COX-2 in the
      prostate tissues of rats with prostatitis pain, and the action mechanism of the
      drug alleviating the prostatitis pain. METHODS: Sixty male Wistar rats were
      randomized into two groups, 10 as blank controls, injected with aqua pro
      injection into the ventral part of prostate, and the other 50 as prostatitis pain
      models, given complete Freund's adjuvant (CFA). Three days later, the pain model
      rats were again equally divided into 5 subgroups: model control, Celecoxib
      Capsules, high-, median- and low-dose Xiaojin Wan, receiving intragastric
      administration of distilled water, Celecoxib Capsules and different doses of
      Xiaojin Wan respectively for 4 weeks. Then they were killed, the harvested
      tissues fixed with 10% paraformaldehyde and the changes of the COX-2 expression
      in the prostate detected with the immunohistochemical technique and graphics
      video analysis system. RESULTS: The expression of COX-2 was strong in the model
      group, significantly lower in the high- and median-dose and the Celecoxib
      Capsules groups than in the model control (P < 0.01) as well as in the high-dose
      than in the median- and low-dose groups (P < 0.01). CONCLUSION: Xiaojin Wan may
      alleviate prostatitis pain by inhibiting the expression of COX-2 in prostate
      tissues.

PMID- 18817355
TI  - Chemical and pharmacological research of the plants in genus Euphorbia.

PMID- 18817356
TI  - Molecular simulations of zeolites: adsorption, diffusion, and shape selectivity.

PMID- 18817357
TI  - Synthesis, characterization, and applications of group 13 cationic compounds.

PMID- 18817359
TI  - Autobiography of Stephen R. Leone.

PMID- 18817358
TI  - Introductory tribute to Stephen R. Leone.

PMID- 18817361
TI  - Publications of stephen R. Leone.

PMID- 18817362
TI  - Direct evaluation of cyclic contributions to the pi energy of conjugated
      hydrocarbons from strongly localized zero-order pictures.
AB  - This paper presents a new procedure for identifying that part of the pi
      electronic energy of conjugated hydrocarbons which results from cyclic
      circulation of electrons around a ring. It first shows that one may calculate
      perturbatively the ground state energy of the Huckel Hamiltonian from a strongly
      localized Kekule-type zero-order wave function. The contributions due to cyclic
      circulation of the electrons appear explicitly, in terms of the interatomic
      hopping integral t, at the second order in cyclobutadiene (where it is equal to 
      t (antiaromatic)) and at third order in benzene, where its value is 0.5t
      (aromatic). Conjugated isomers of benzene are also considered. The cyclic
      circulation contributions for an N-membered ring are shown to depend strongly on
      the molecular graph in which it is embedded. A general expression is found for
      the cyclic contribution to the pi energy of a ring, the Kekule graph of which
      contains N double bonds alternating with N single bonds. It is the energy of the
      ring, plus the sum of the energies of the N subsystems that result from one
      double-bond removal, minus the sum of the energies of the N open systems that
      result from one single-bond cut. This new aromaticity index, ACE(MC), may be seen
      as the enthalpy of a hyperhomodesmotic chemical equation. In contrast to the
      index ACE(DC) previously defined from a double cut of the ring, the multiple-cut
      ACE(MC) exhibits the expected asymptotic disappearance of the cyclic energy as
      the ring size tends to infinity. In the multiple-cut approach, aromaticity
      persists in bond-alternating rings, but, in contrast to the total pi energy, the
      purely cyclic contribution tends to resist distortion. Extension of the approach
      to charged, branched and heterosubstituted rings are discussed, as well as its ab
      initio transcription.

PMID- 18817363
TI  - Structure-activity relationships in 1,4-benzodioxan-related compounds. 9. From
      1,4-benzodioxane to 1,4-dioxane ring as a promising template of novel alpha1D
      adrenoreceptor antagonists, 5-HT1A full agonists, and cytotoxic agents.
AB  - Novel 1,4-dioxane compounds structurally related to WB 4101 (1) were prepared in
      order to investigate the possibility that the quite planar 1,4-benzodioxane
      template of 1 might be replaced by the less conformationally constrained 1,4
      dioxane ring. The biological profiles of the new compounds were assessed using
      binding assays at human cloned alpha 1-adrenoreceptor (alpha 1-AR) subtypes and 5
      HT 1A receptors, expressed in Chinese hamster ovary and HeLa cell membranes,
      respectively, and by functional experiments in isolated rat vas deferens (alpha
      1A), spleen (alpha 1B), and aorta (alpha 1D). Moreover, the cytotoxic effects of
      the novel compounds were determined in PC-3 prostate cancer cells. The results
      showed that the properly substituted 1,4-dioxane nucleus proved to be a suitable
      scaffold for selective alpha 1D-AR antagonists (compound 14), potential
      anticancer agents (compound 13), and full 5-HT 1A receptor agonists (compound
      15). In particular, compound 15 may represent a novel lead in the development of
      highly potent 5-HT 1A receptor full agonists useful as antidepressant and
      neuroprotective agents.

PMID- 18817364
TI  - 3-amino-7-phthalazinylbenzoisoxazoles as a novel class of potent, selective, and
      orally available inhibitors of p38alpha mitogen-activated protein kinase.
AB  - The p38 mitogen-activated protein kinase (MAPK) is a central signaling molecule
      in many proinflammatory pathways, regulating the cellular response to a multitude
      of external stimuli including heat, ultraviolet radiation, osmotic shock, and a
      variety of cytokines especially interleukin-1beta and tumor necrosis factor
      alpha. Thus, inhibitors of this enzyme are postulated to have significant
      therapeutic potential for the treatment of rheumatoid arthritis, inflammatory
      bowel disease, osteoporosis, and many other diseases where aberrant cytokine
      signaling is the driver of disease. Herein, we describe a novel class of 3-amino
      7-phthalazinylbenzoisoxazole-based inhibitors. With relatively low molecular
      weight, these compounds are highly potent in enzyme and cell-based assays, with
      minimal protein shift in 50% human whole blood. Compound 3c was efficacious (ED
      50 = 0.05 mg/kg) in the rat collagen induced arthritis (CIA) model.

PMID- 18817365
TI  - Discovery of highly selective and potent p38 inhibitors based on a phthalazine
      scaffold.
AB  - Investigations into the structure-activity relationships (SAR) of a series of
      phthalazine-based inhibitors of p38 are described. These efforts originated from
      quinazoline 1 and through rational design led to the development of a series of
      orally bioavailable, potent, and selective inhibitors. Kinase selectivity was
      achieved by exploiting a collection of interactions with p38alpha including close
      contact to Ala157, occupation of the hydrophobic gatekeeper pocket, and a residue
      flip with Gly110. Substitutions on the phthalazine influenced the pharmacokinetic
      properties, of which compound 16 displayed the most desirable profile. Oral
      dosing (0.03 mg/kg) of 16 in rats 1 h prior to LPS challenge gave a >50% decrease
      in TNFalpha production.

PMID- 18817366
TI  - Isosorbide-2-carbamate esters: potent and selective butyrylcholinesterase
      inhibitors.
AB  - In this study, we report the SAR and characterization of two groups of isosorbide
      based cholinesterase inhibitors. The first was based directly on the clinically
      used nitrate isosorbide mononitrate (ISMN) retention of the 5-nitrate group and
      introduction of a series of 2-carbamate functionalities. The compounds proved to
      be potent and selective inhibitors of human plasma butyrylcholinesterase (
      huBuChE). In the second group, the nitrate ester was removed and replaced with a
      variety of alkyl and aryl esters. These generally exhibited nanomolar potency
      with high selectivity for BuChE over acetylcholinesterase (AChE). The most potent
      and selective compound was isosorbide-2-benzyl carbamate-5-benzoate with an IC 50
      of 4.3 nM for BuChE and >50000 fold selectivity over human erythrocyte AChE.
      Inhibition with these compounds is time-dependent, competitive, and slowly
      reversible, indicating active site carbamylation.

PMID- 18817367
TI  - Rotationally constrained 2,4-diamino-5,6-disubstituted pyrimidines: a new class
      of histamine H4 receptor antagonists with improved druglikeness and in vivo
      efficacy in pain and inflammation models.
AB  - A new structural class of histamine H 4 receptor antagonists (6-14) was designed
      based on rotationally restricted 2,4-diaminopyrimidines. Series compounds showed
      potent and selective in vitro H 4 antagonism across multiple species, good CNS
      penetration, improved PK properties compared to reference H 4 antagonists,
      functional H 4 antagonism in cellular and in vivo pharmacological assays, and in
      vivo anti-inflammatory and antinociceptive efficacy. One compound, 10 (A-943931),
      combined the best features of the series in a single molecule and is an excellent
      tool compound to probe H 4 pharmacology. It is a potent H 4 antagonist in
      functional assays across species (FLIPR Ca (2+) flux, K b < 5.7 nM), has high
      (>190x) selectivity for H 4, and combines good PK in rats and mice (t 1/2 of 2.6
      and 1.6 h, oral bioavailability of 37% and 90%) with anti-inflammatory activity
      (ED 50 = 37 micromol/kg, mouse) and efficacy in pain models (thermal
      hyperalgesia, ED 50 = 72 micromol/kg, rat).

PMID- 18817368
TI  - Discovery of 1,4-substituted piperidines as potent and selective inhibitors of T
      type calcium channels.
AB  - The discovery of a novel series of potent and selective T-type calcium channel
      antagonists is reported. Initial optimization of high-throughput screening leads
      afforded a 1,4-substituted piperidine amide 6 with good potency and limited
      selectivity over hERG and L-type channels and other off-target activities.
      Further SAR on reducing the basicity of the piperidine and introducing polarity
      led to the discovery of 3-axial fluoropiperidine 30 with a significantly improved
      selectivity profile. Compound 30 showed good oral bioavailability and brain
      penetration across species. In a rat genetic model of absence epilepsy, compound
      30 demonstrated a robust reduction in the number and duration of seizures at 33
      nM plasma concentration, with no cardiovascular effects at up to 5.6 microM.
      Compound 30 also showed good efficacy in rodent models of essential tremor and
      Parkinson's disease. Compound 30 thus demonstrates a wide margin between CNS and
      peripheral effects and is a useful tool for probing the effects of T-type calcium
      channel inhibition.

PMID- 18817369
TI  - A conducting coordination polymer based on assembled Cu9 cages.
AB  - We report on a novel highly semiconducting 1D coordination polymer architecture
      obtained by the reaction of a Cu(II) salt with 2,2'-dipyridyldisulfide under
      microwave solvothermal conditions. This reaction proceeds with an unusual C-S and
      S-S bond cleavage of the 2,2'-dipyridyldisulfide ligand. The unprecedented
      architecture of this coordination polymer consists of a 1D chain formed by the
      assembling of Cu9 cluster cages. The electrical conductivity behavior of this
      novel material suggests new perspectives for the use of coordination polymers as
      electrical conducting materials.

PMID- 18817370
TI  - Syntheses, X-ray structures, solid state high-field electron paramagnetic
      resonance, and density-functional theory investigations on chloro and aqua Mn(II)
      mononuclear complexes with amino-pyridine pentadentate ligands.
AB  - The two pentadentate amino-pyridine ligands L5(2) and L5(3) (L5(2) and L5(3)
      stand for the N-methyl-N,N',N'-tris(2-pyridylmethyl)ethane-1,2-diamine and the N
      methyl-N,N',N'-tris(2-pyridylmethyl)propane-1,3-diamine, respectively) were used
      to synthesize four mononuclear Mn(II) complexes, namely [(L5(2))MnCl](PF6)
      (1(PF6)), [(L5(3))MnCl](PF6) (2(PF6)), [(L5(2))Mn(OH2)](BPh4)2 (3(BPh4)2), and
      [(L5(3))Mn(OH2)](BPh4)2 (4(BPh4)2). The X-ray diffraction studies revealed
      different configurations for the ligand L5(n) (n = 2, 3) depending on the sixth
      exogenous ligand and/or the counterion. Solid state high-field electron
      paramagnetic resonance spectra were recorded on complexes 1-4 as on previously
      described mononuclear Mn(II) systems with tetra- or hexadentate amino-pyridine
      ligands. Positive and negative axial zero-field splitting (ZFS) parameters D were
      determined whose absolute values ranged from 0.090 to 0.180 cm(-1). Density
      functional theory calculations were performed unraveling that, in contrast with
      chloro systems, the spin-spin and spin-orbit coupling contributions to the D
      parameter are comparable for mixed N,O-coordination sphere complexes.

PMID- 18817371
TI  - High-connectivity networks and hybrid inorganic rod materials built from
      potassium and rubidium p-halide-substituted aryloxides.
AB  - A series of complex networks have been synthesized from the association of
      potassium and rubidium p-halide-substituted aryloxides using 1,4-dioxane
      molecules as neutral linkers. The crystalline polymers [(4-F-C6H4OK)6 x
      (dioxane)4]infinity (1), [(4-I-C6H4OK)6 x (dioxane)6]infinity (2), and [(4-I
      C6H4ORb)6 x (dioxane)6]infinity (3) are built from discreet, hexameric M6O6
      aggregates. Compound 1 forms an unusual 16-connected framework involving both K-F
      and K-O(diox) interactions. Each hexamer connects to eight neighboring aggregates
      through double-bridging contacts, resulting in a body-centered cubic (bcu)
      topology. Compounds 2 and 3 are isostructural, 12-connected networks, where each
      aggregate utilizes six dioxane double bridges to form primitive cubic (pcu) nets.
      In contrast, the complexes [(4-Cl-C6H4OK)3 x (dioxane)]infinity (4), [(4-Br
      C6H4OK)2 x (dioxane)0.5]infinity (5), and [(4-Br-C6H4ORb)5 x (dioxane)5]infinity
      (6) are built from one-dimensional (1D) inorganic rods composed solely of M-O(Ar)
      interactions. The extended structures of both 4 and 5 can be described as pcu
      nets, where parallel 1D inorganic pillars are connected through dioxane bridges.
      Compound 6 is also composed of parallel 1D inorganic rods, but in this instance
      the coordinated dioxane molecules do not bridge, resulting in isolated, close
      packed chains in the solid state.

PMID- 18817372
TI  - Uniform colloidal alkaline earth metal fluoride nanocrystals: nonhydrolytic
      synthesis and luminescence properties.
AB  - In this paper, we present a facile and general synthetic route to high-quality
      alkaline earth metal fluoride (AEF2, AE = Ca, Sr, Ba) nanocrystals and
      CaF2:Tb(3+) nanocrystals based on the thermal decomposition of corresponding
      trifluoroacetate precursors in hot oleylamine. X-ray diffraction, transmission
      electron microscopy, thermogravimetric and differential thermal analysis, Fourier
      transform infrared spectra, photoluminescence spectra, and kinetic decays were
      employed to characterize the samples. The use of single-source precursors plays
      an important role in the formation of high-quality AEF 2 nanocrystals, and the
      formation process is demonstrated in detail. The obtained AEF2 nanocrystals are
      nearly monodisperse in size and highly crystalline, and they can be well
      dispersed in nonpolar solvents to form stable and clear colloidal solutions,
      which all display purple emissions under ultraviolet excitation due to the
      numerous surface defects of nanocrystals with large surface/volume ratios.
      Furthermore, we demonstrate the feasibility of introducing Tb(3+) ions into the
      CaF2 host via this method, which shows strong green emission corresponding to the
      characteristic (5)D4-(7)F(J) (J = 3, 4, 5, 6) emission of Tb(3+) ions, which can
      be potentially used as labels for biological molecules.

PMID- 18817373
TI  - Molecular wheels: new Mn12 complexes as single-molecule magnets.
AB  - The preparation, structure and magnetic properties of three new wheel-shaped
      dodecanuclear manganese complexes, [Mn12(Adea)8(CH3COO)14] x 7 CH3CN (1 x
      7CH3CN), [Mn12(Edea)8(CH3CH2COO)14] (2) and [Mn12(Edea)8(CH3COO)2(CH3CH2COO)12]
      (3), are reported, where Adea(2-) and Edea(2-) are dianions of the N-allyl
      diethanolamine and the N-ethyl diethanolamine ligands, respectively. Each complex
      has six Mn(II) and six Mn(III) ions alternating in a wheel-shaped topology, with
      eight n-substituted diethanolamine dianions. All variable-temperature direct
      current (DC) magnetic susceptibility data were collected in 1, 0.1, or 0.01 T
      fields and in the 1.8-300 K temperature range. Heat capacity data, collected in
      applied fields of 0-9 T and in the 1.8-100 K temperature range, indicate the
      absence of a phase-transition due to long-range magnetic ordering for 1 and 3.
      Variable-temperature, variable-field DC magnetic susceptibility data were
      obtained in the 1.8-10 K and 0.1-5 T ranges. All complexes show out-of-phase
      signals in the AC susceptibility measurements, collected in a 50-997 Hz frequency
      range and in a 1.8-4.6 K temperature range. Extrapolation to 0 K of the in-phase
      AC susceptibility data collected at 50 Hz indicates an S = 7 ground state for 1,
      2, and 3. Magnetization hysteresis data were collected on a single crystal of 1
      in the 0.27-0.9 K range and on single crystals of 2 and 3 in the 0.1-0.9 K
      temperature range. Discrete steps in the magnetization curves associated with
      resonant quantum tunneling of magnetization (QTM) confirm these complexes to be
      single-molecule magnets. The appearance of extra QTM resonances on the magnetic
      hysteresis of 1 is a result of a weak coupling between two Mn ions at opposite
      ends of the wheel, dividing the molecule into two ferromagnetic exchange-coupled
      S = 7/2 halves. The absence of these features on 2 and 3, which behave as rigid
      spin S = 7 units, is a consequence of different interatomic distances.

PMID- 18817374
TI  - New directions in the preparation and redox chemistry of fluoride-templated
      tetranuclear vanadium phosphonate cage compounds, M(n+)[(V2O3)2(RPO3)4<F]n.
AB  - A new and simple preparation method for fluoride-templated tetranuclear vanadium
      phosphonate cage compounds, M(n+)[(V2O3)2(RPO3)4<F]n is outlined. The crystalline
      products were characterized by X-ray diffraction, elemental analysis, and
      thermogravimetric analysis. Using the acceptable solubility of the products,
      multinuclear NMR could be performed on the corresponding solutions. Some insight
      into the process of formation of the cage compounds in solution could be reached
      by monitoring the corresponding reaction mixture by multinuclear NMR. The
      template function of the F(-) ion could be demonstrated together with the fact
      that the non-transition-metal ions (M(n+)) used here (phosphonium ions) have no
      direct effect on the formation of the cage. In contrast, the redox behavior of
      these compounds in the solid state distinctly depends on the cations. This could
      be easily investigated by electron paramagnetic resonance because the mixed
      valence species (3V(V)/V(IV)) can be produced chemically or thermally induced in
      solution as well as in the solid state. In the latter case, the reaction of the
      cage with H2 activated on the platinum powder can be regarded as a key experiment
      for understanding the redox process of the title compounds in the solid state.
      The role of specific interactions in solution at the tumbling rate and the
      localization of spin density in the cage could be demonstrated by the reduction
      performed with 1-methylimidazole and quinoline. While the substituents R = Me and
      Ph have only a small influence on the cage formation in solution, they have a
      significant influence on the redox reaction and structural relaxation in the
      solid state.

PMID- 18817375
TI  - Dimolybdenum bis-2,4,6-triisopropyl-benzoate bis-4-isonicotinate: a redox active
      analogue of 4,4'-bipyridine with ambivalent properties.
AB  - The reaction between Mo2(TiPB)4 and 4-iso-nicotinic acid (2 equiv) in ethanol
      leads to the formation of trans-Mo2(TiPB)2(nic)2, I, where TiPB = 2,4,6
      triisopropylbenzoate and nic = 4-isonicotinate. The molecular structures of I and
      I x 2DMSO were determined in the solid state by a single-crystal X-ray study, and
      its electronic structure was determined by DFT calculations on a model compound,
      where formate ligands were substituted for the bulky TiPB. The physicochemical
      properties of I are reported, and its potential as a redox active building block,
      a quasi-metalloorganic analogue of 4,4'-bipyridine, is described in the synthesis
      of molecular and solid-state assemblies. The molecular structure of I in the
      solid state consists of a 3-dimensional network in which each unit of
      Mo2(TiPB)2(nic)2 acts as a donor and acceptor via N to Mo coordination. In the
      structure of I x 2DMSO, the DMSO ligands coordinate axially with the Mo-Mo bond
      via oxygen. The reaction between I and Rh2(O2CMe)4 is shown to give a 1-D
      polymeric chain in the solid state: [{Rh2(O2CMe)4}{Mo2(TiPB)2(nic)2}] infinity,
      II. A similar structure was found for the product involving Rh2(O2CCMe3)4.
      Evidence is also reported for the formation of [(1,5-COD)MePt]2[mu
      Mo2(TiPB)2(nic)2](PF6)2, III, and [(1,5-COD)Pt(mu-I)(PF6)2]n.

PMID- 18817376
TI  - Hexanuclear cobalt carbonyl carbide clusters: the interplay between octahedral
      and trigonal prismatic structures.
AB  - The six-vertex cobalt carbonyl clusters [Co6C(CO)n](2-) (n = 12, 13, 14, 15, 16)
      with an interstitial carbon atom have been studied by density functional theory
      (DFT). These DFT studies indicate that the experimentally known structure of
      [Co6C(CO)15](2-) consisting of a Co6 trigonal prism with each of its edges
      bridged by carbonyl groups is a particularly stable structure lying more than 20
      kcal/mol below any other [Co6C(CO)15](2-) structure. Addition of a CO group to
      this [Co6C(CO)15](2-) structure gives the lowest energy [Co6C(CO)16](2-)
      structure, also a Co6 trigonal prism with one of the vertical edges bridged by
      two CO groups and the remaining eight edges each bridged by a single CO group.
      However, this [Co6C(CO)16](2-) structure is thermodynamically unstable with
      respect to CO loss reverting to the stable trigonal prismatic [Co6C(CO)15](2-).
      This suggests that 15 carbonyl groups is the maximum that can be attached to a
      Co6C skeleton in a stable compound. The lowest energy structure of [Co6C(CO)14](2
      ) has a highly distorted octahedral Co6 skeleton and is thermodynamically
      unstable with respect to disproportionation to [Co6C(CO)15](2-) and
      [Co6C(CO)13](2-). The lowest energy [Co6C(CO)13](2-) structure is very similar to
      a known stable structure with an octahedral Co6 skeleton. The lowest energy
      [Co6C(CO)12](2-) structure is a relatively symmetrical D3d structure containing a
      carbon-centered Co6 puckered hexagon in the chair form.

PMID- 18817377
TI  - Synthetic route to dinuclear platinum(II) complexes [{trans-PtCl(NH3)2}2(mu-L)]2+
      (L = aliphatic or heterocyclic diamine) as potential antitumor agents, exploiting
      the mutual activation of hydroxido ligands and ammonium groups.
AB  - A simple and efficient method for the synthesis of potentially antitumor-active
      dinuclear platinum complexes of the general formula [{trans-PtCl(NH3)2}2(mu
      L)]((n+2)+) (L = aliphatic or heterocyclic diamine; n = charge of L) is
      presented. The procedure is based on the mutual in situ activation of trans
      [PtCl(OH)(NH3)2] and the linker L in the form of a diammonium salt. This
      synthetic pathway yielded the Farrell compound [{trans-PtCl(NH3)2}2{mu
      NH2(CH2)6NH2}]Cl2 (BBR3005) in quantitative yield. Using the same procedure, we
      prepared the new pyrazolate-bridged compound [{trans-PtCl(NH3)2}2(mu-pz)]Cl,
      determined its X-ray structure, and tested its cytotoxicity against three wild
      type and one cisplatin-resistant cell lines.

PMID- 18817378
TI  - Metal-metal communication in copper(II) complexes of cyclotetraphosphazene
      ligands.
AB  - Copper(II) chloride and bromide react with the pyridyloxy-substituted
      cyclotetraphosphazene ligands, octakis(2-pyridyloxy)cyclotetraphosphazene (L(1)),
      and octakis(4-methyl-2-pyridyloxy)cyclotetraphosphazene (L(2)), to form the
      dimetallic complexes, [L(CuX2)2] (L = L(1), X = Br; L = L(2), X = Cl or Br), and
      [{L(1)(CuCl2)2}n]. Single crystal X-ray crystallography shows the complex
      [{L(1)(CuCl2)2}n] to be a coordination polymer propagated by interligand "Cu(mu
      Cl)2Cu" bridges whereas [L(2)(CuCl2)2] forms discrete dimetallic
      cyclotetraphosphazene-based moieties. The variable temperature magnetic
      susceptibility data for [{L(1)(CuCl2)2}n] are consistent with a weak
      antiferromagnetic exchange interaction between the copper(II) centers occurring
      via the bridging chloride ions. [L(2)(CuCl2)2] and [L(CuBr2)2] (L = L(1) and
      L(2)) exhibit normal Curie-like susceptibilities. The abstraction of a chloride
      ion, using [Ag(MeCN)4](PF6), from each copper site in [L(2)(CuCl2)2], affords the
      new complex, [L(2)(CuCl)2](PF6)2, in which the two copper(II) ions are separated
      by "N-P=N-P=N" phosphazene bridges. Electron spin resonance and variable
      temperature magnetic measurements indicate the occurrence of weak
      antiferromagnetic coupling between the unpaired electrons on the copper(II)
      centers. Density Functional Theory (DFT) calculations on the [L(2)(CuCl)2](2+)
      dication and the related cyclotriphosphazene complex, [L(4)(CuCl2)2] (L(4) =
      hexakis(4-methyl-2-pyridyloxy)cyclotriphosphazene), have identified "electron
      density-bridge" molecular orbitals which involve Cu 3d orbitals overlapping with
      the non-bonding N-based molecular orbitals on the phosphazene rings as the
      pathway for this interaction.

PMID- 18817379
TI  - Density functional theory study of the structural, electronic, and magnetic
      properties of a mu-oxo bridged dinuclear Fe(IV) complex based on a tetra-amido
      macrocyclic ligand.
AB  - Recently, the synthesis, crystallographic structure, and Mossbauer
      characterization of the first example of an [(Fe(IV)TAML)2O](2-) (TAML = tetra
      amido microcyclic ligand) complex were reported. Here, we elucidate the prominent
      structural, electronic, and magnetic properties of this complex on the basis of
      density functional theory (DFT) calculations. While the torsion between the
      molecular halves is caused by hydrogen bonding between the TAML moieties, the
      bending of the Fe-O-Fe unit is an intrinsic property of the bridge. The values
      for the (57)Fe isomer shift and quadrupole splitting obtained with DFT are in
      good agreement with experimental results and indicate that the irons have
      intermediate spin states (S1 = S2 = 1). The iron spins are coupled by strong
      antiferromagnetic exchange to yield a ground state with system spin S = 0. The Fe
      O distances in the excited S > 0 states are significantly longer than in the
      ground state. Since the wave function of the ground state, in which the iron
      spins are antiferromagnetically coupled to give system spin S = 0, is a linear
      combination of Slater determinants that cannot be treated with existing DFT
      codes, the Fe-O distance for the S = 0 state has been estimated by extrapolation
      from the optimized geometries for the ferromagnetic state (S = 2) and the broken
      symmetry state to be 1.748 A, in good agreement with the crystallographic
      distance 1.728 A. To accommodate the spin-dependent reorganization energies, the
      conventional bilinear spin Hamiltonian has been extended with a biquadratic
      coupling term: H(ex) = c' + j0S1 x S2 + j1(S1 x S2)(2). A computational scheme is
      presented for estimating the exchange parameters, yielding the values j0 = 199
      cm(-1) and j1 = -61 cm(-1) for [(Fe(IV)B*)2O](2-). Two mechanisms for biquadratic
      exchange are discussed.

PMID- 18817380
TI  - Alternative polyadenylation: a twist on mRNA 3' end formation.
AB  - Regulation of gene expression by RNA processing mechanisms is now understood to
      be an important level of control in mammalian cells. Regulation at the level of
      RNA transcription, splicing, polyadenylation, nucleo-cytoplasmic transport, and
      translation into polypeptides has been well-studied. Alternative RNA processing
      events, such as alternative splicing, also have been recognized as key
      contributors to the complexity of mammalian gene expression. Pre-messenger RNAs
      (pre-mRNAs) may be polyadenylated in several different ways due to more than one
      polyadenylation signal, allowing a single gene to encode multiple mRNA
      transcripts. However, alternative polyadenylation has only recently taken the
      field as a major player in gene regulation. This review summarizes what is
      currently known about alternative polyadenylation. It covers results from
      bioinformatics, as well as those from investigations of viral and tissue-specific
      studies and, importantly, will set the stage for what is yet to come.

PMID- 18817381
TI  - Entropy- and hydrolytic-driven positional switching of macrocycle between imine-
      and hydrogen-bonding stations in rotaxane-based molecular shuttles.
AB  - The construction and switching properties of a novel class of molecular shuttles
      1 with imine-bonding stations for macrocyclic diamine parts are reported. Studies
      on dithioacetalized [2]rotaxane 4 with two hydrogen-bonding stations and a masked
      imine-bonding station showed that protonation of a macrocycle increases the
      shuttling barrier due to hydrogen-bond formation between NH 3 (+) groups and the
      TEG-stations. Hydrolysis of the imine-bonds of the imine-bridged molecular
      shuttles 1b, c with TEG-stations could exclusively give the [2]rotaxane 2b, c.2H
      (2+), with the macrocycle hydrogen-bonded with the TEG-station. In contrast, 1a
      without TEG-stations gave an equilibrated mixture of 1a, monoimine 3a.H (+), and
      2a.2H (2+) under similar acidic hydrolytic conditions. The equilibrium between
      1b, c and 2b, c.2H (2+) to control the position of the macrocycle could be
      successfully switched to either side by applying acidic hydrolytic or dehydrating
      conditions. Furthermore, the equilibrium was largely biased to [2]rotaxane 2b,
      c.2H (2+) under acidic hydrolytic conditions and could be reversed in favor of
      bis-imine 1b, c just by heating. This is a successful example of a molecular
      shuttle exhibiting entropy-driven translational isomerism with remarkable
      positional discrimination. An examination of thermodynamic parameters showed that
      imine-bond hydrolyses and the formation of hydrogen bonds between the macrocycle
      and the station are thermodynamically matched processes, because both processes
      are enthalpically favored and accompanied by a loss of entropy. The combination
      of imine-bonding and hydrogen-bonding station in a rotaxane system is the key to
      realizing the clear entropy-driven positional switching of the macrocycle
      observed.

PMID- 18817382
TI  - Integrative self-sorting: construction of a cascade-stoppered hetero[3]rotaxane.
AB  - In this Communication, a competing self-sorting system containing benzo-21-crown
      7, dibenzo-24-crown-8 and two secondary ammonium salts is constructed, which is
      then modified to achieve a hetero[3]pseudorotaxane with a specific sequence of
      wheels. With these two systems, we successfully demonstrate the concept of
      integrative self-sorting, and their relation. Furthermore, based on this self
      sorting scheme, a hetero[3]rotaxane with an efficient stopper cascade has been
      synthesized.

PMID- 18817383
TI  - A new zirconium inorganic building brick forming metal organic frameworks with
      exceptional stability.
AB  - Porous crystals are strategic materials with industrial applications within
      petrochemistry, catalysis, gas storage, and selective separation. Their unique
      properties are based on the molecular-scale porous character. However, a
      principal limitation of zeolites and similar oxide-based materials is the
      relatively small size of the pores, typically in the range of medium-sized
      molecules, limiting their use in pharmaceutical and fine chemical applications.
      Metal organic frameworks (MOFs) provided a breakthrough in this respect. New MOFs
      appear at a high and an increasing pace, but the appearances of new, stable
      inorganic building bricks are rare. Here we present a new zirconium-based
      inorganic building brick that allows the synthesis of very high surface area MOFs
      with unprecedented stability. The high stability is based on the combination of
      strong Zr-O bonds and the ability of the inner Zr6-cluster to rearrange
      reversibly upon removal or addition of mu3-OH groups, without any changes in the
      connecting carboxylates. The weak thermal, chemical, and mechanical stability of
      most MOFs is probably the most important property that limits their use in large
      scale industrial applications. The Zr-MOFs presented in this work have the
      toughness needed for industrial applications; decomposition temperature above 500
      degrees C and resistance to most chemicals, and they remain crystalline even
      after exposure to 10 tons/cm2 of external pressure.

PMID- 18817384
TI  - Gd5-xYxTt4 (Tt = Si or Ge): effect of metal substitution on structure, bonding,
      and magnetism.
AB  - A crystallographic study and theoretical assessment of the Gd/Y site preferences
      in the Gd 5- x Y x Tt 4 ( Tt = Si, Ge) series prepared by high-temperature
      methods is presented. All structures for the Gd 5- x Y x Si 4 system belong to
      the orthorhombic, Gd 5Si 4-type (space group Pnma). For the Gd 5- x Y x Ge 4
      system, phases with x < 3.6 and x >or= 4.4 adopt the orthorhombic, Sm 5Ge 4-type
      structure. For the composition range of 3.6 <or= x <or= 4.2, a monoclinic, U 2Mo
      3Si 4-type structure (space group P2 1/ c) occurs as the majority phase. This
      structure type has not been previously observed in the RE 5 T 4 (T = Si, Ge, Ga)
      system and differs from the known monoclinic structure of Gd 5Si 2Ge 2-type
      (space group P2 1/ a) because all Ge...Ge contacts between slabs are equivalent.
      The structural relationships between the Sm 5Ge 4-type and the U 2Mo 3Si 4-type
      structures are discussed. Single crystal refinements of the occupancies for the
      three sites for Gd/Y atoms in the asymmetric unit reveal a partially ordered
      arrangement of Gd and Y atoms. TB-LMTO-ASA calculations were performed to study
      these atomic distributions as well as to elucidate possible electronic forces
      that might drive the structural variation. These results illustrate the
      importance of one of the Gd/Y-sites in shaping the magnetic and structural
      features observed in Gd 5- x Y x Tt 4 system. The magnetic properties of some of
      the Gd 5- x Y x Tt 4 phases are also reported. Germanides with x <or= 2 show a
      metamagnetic-type transition similar to Gd 5Ge 4 from 57-92(2) K. As the Y
      concentration increases (3 <or= x <or= 4), these phases exhibit at least
      ferrimagnetic ordering with transition temperatures ranging from 15-31(2) K to
      the paramagnetic state.

PMID- 18817386
TI  - Probing the self-assembly of inorganic cluster architectures in solution with
      cryospray mass spectrometry: growth of polyoxomolybdate clusters and polymers
      mediated by silver(I) ions.
AB  - Cryospray mass spectrometry (CSI-MS) has been used to probe the mechanism of self
      assembly of polyoxometalate clusters in solution. By using CSI-MS and electronic
      absorbance spectroscopy it was possible to monitor in real-time the self-assembly
      of polymeric chains based on [Ag 2Mo 8O 26] (2-) n building blocks. The role of
      the Ag (I) ion in the solution state rearrangement of molybdenum Lindqvist ({Mo
      6}) into the silver-linked beta-octamolybdate ({Mo 8}) structure (( n-C 4H 9) 4N)
      2 n [Ag 2Mo 8O 26] n ( 1) is revealed in unprecedented detail. A monoanionic
      series, in particular [AgMo m O 3 m+1 ] (-) where m = 2 to 4, and series
      involving mixed oxidation state polyoxomolybdate species, which illustrate the in
      solution formation of the (Ag{Mo 8}Ag) building blocks, have been observed. CSI
      MS detection of species with increasing metal nuclearity concomitant with
      increasing organic cation contribution supports the hypothesis that the organic
      cations used in the synthesis play an important structure-directing role in
      polyoxometalate (POM) growth in solution. A real-time decrease in [{Mo 6}] and
      associated increase in [{Mo 8}] have been observed using CSI-MS and electronic
      absorbance spectroscopy, and the rate of {Mo 6} interconversion to {Mo 8} was
      found to decrease on increasing the size of the countercation. This result can be
      attributed to the steric bulk of larger organic groups hindering {Mo 6} to {Mo 8}
      rearrangement and hindering the contact between silver cations and molybdenum
      anions.

PMID- 18817387
TI  - Mechanism of photocatalytic water splitting in TiO2. Reaction of water with
      photoholes, importance of charge carrier dynamics, and evidence for four-hole
      chemistry.
AB  - We show for the first time that the photogenerated hole lifetime in TiO 2 is a
      strong determinant of the ability of TiO 2 to split water. Hole lifetimes were
      measured using transient absorption spectroscopy over a range of excitation
      intensities. The lifetimes of the holes were modulated by the use of exogenous
      scavengers and were also found to vary systematically with the excitation
      intensity. In all cases the quantum yield of oxygen production is found to be
      linked to the light intensity used, ranging from below 1 sun equivalent to nearly
      1 sun equivalent. We also provide evidence that oxygen production requires four
      photons for each molecule of oxygen, which is reminiscent of the natural
      photosynthetic water-splitting mechanism. This in turn suggests a mechanism for
      oxygen production which requires four-hole chemistry, presumably via three, as
      yet unidentified intermediates. It is also shown that at excitation densities on
      the order of 1 sun, nongeminate electron-hole recombination limits the quantum
      yield significantly.

PMID- 18817388
TI  - Putting ammonia into a chemically opened fullerene.
AB  - We put ammonia into an open-cage fullerene with a 20-membered ring ( 1) as the
      orifice and examined the properties of the complex using NMR and MALDI-TOF mass
      spectroscopy. The proton NMR shows a broad resonance corresponding to endohedral
      NH 3 at delta H = -12.3 ppm relative to TMS. This resonance was seen to narrow
      when a (14)N decoupling frequency was applied. MALDI spectroscopy confirmed the
      presence of both 1 ( m/ z = 1172) and 1 + NH 3 ( m/ z = 1189), and integrated
      intensities of MALDI peak trains and NMR resonances indicate an incorporation
      fraction of 35-50% under our experimental conditions. NMR observations showed a
      diminished incorporation fraction after 6 months of storage at -10 degrees C,
      which indicates that ammonia slowly escapes from the open-cage fullerene.

PMID- 18817389
TI  - Total synthesis of (+)-cassaine via transannular Diels-Alder reaction.
AB  - A full account of the total synthesis of (+)-cassaine ( 1) using the transannular
      Diels-Alder (TADA) reaction as the pivotal construction is described. The
      strategy began from Evans' oxazolidine 8, the only chiral source used for the
      total stereochemical outcome of the target molecule. The key intermediate 3 was
      obtained from 8 in 10 steps in 40% overall yield. Following extensive
      optimization, the coupling of 3 on both ends with another densely functional
      partner 2 followed by TADA reaction on macrocycle 4 cleanly furnished the
      tricycle 5. The stereochemical outcome in 5 was expected via a least-energetic
      transition state T4. A stereoselective reduction, hydroboration, and methyl
      cuprate 1,4-addition along with a few other functional interconversions
      transformed 5 into the key intermediate 37. Final tethering of
      dimethylaminoethyloxycarbonyl along with epimerization at C8 and alcohol
      deprotection at C3 yielded the natural product 1.

PMID- 18817390
TI  - Formation and spectroscopy of a tryptophan radical containing peptide in the gas
      phase.
AB  - A doubly deprotonated tryptophan containing peptide was electrosprayed and
      isolated in an ion trap. UV excitation on this peptide leads to electron
      detachment and to the formation of an indolyl radical. The photogenerated radical
      was fragmented by a second laser. The visible spectrum of the gas-phase neutral
      tryptophan radical containing peptide has been recorded and constitutes a
      benchmark for calculations and optical measurements.

PMID- 18817391
TI  - Two-coordinate d9 complexes. synthesis and oxidation of NHC nickel(I) amides.
AB  - Reaction of the d9-d9 Ni(I) monochloride dimer, [(IPr)Ni(mu-Cl)]2 (1), with
      NaN(SiMe3)2 and LiNHAr (Ar = 2,6-diisopropylphenyl) gives the novel monomeric, 2
      coordinate Ni(I) complexes (IPr)Ni{N(SiMe3)2} (2) and (IPr)Ni(NHAr) (3). Reaction
      of 2 with Cp2Fe+ results in its 1-e- oxidation followed by beta-Me elimination to
      give a base-stabilized iminosilane complex [(IPr)Ni(CH3){kappa1
      N(SiMe3)=SiMe2.Et2O}][BArF4] (6). Oxidation of 3 gives [(IPr)Ni(eta3
      NHAr)(THF)][BArF4] (4), which upon loss of THF affords dimeric
      [(IPr)Ni(N,eta3:NHC6iPr2H3)]2[BArF4]2 (5).

PMID- 18817392
TI  - Origin of enantioselectivity in CF3-PIP-catalyzed kinetic resolution of secondary
      benzylic alcohols.
AB  - Computational studies provide support for the involvement of intermolecular pi
      interactions in the chiral recognition of secondary benzylic alcohols by the
      enantioselective acyl transfer catalyst CF3-PIP.

PMID- 18817393
TI  - Networking of calixcrowns: from heteronuclear endo/exocyclic coordination
      polymers to a photoluminescence switch.
AB  - Solvato-PL switching and shrinking-and-opening process: we present two CuI
      coordination polymers of calix[4]-bis-monothiacrown (L) obtained in the absence
      (1) and presence (2) of KI. The structures show not only very unusual CuI-based
      network arrangements but also unique reversible photolunimescence switching
      behavior induced by removal of coordinated solvent. Furthermore, upon inclusion
      of K+ ions the crown ring shrinks leading to "opening" of opposite aromatic rings
      in the host calixarene unit, rare behavior for this class of compound.

PMID- 18817394
TI  - Bilayer in small bicelles revealed by lipid-protein interactions using NMR
      spectroscopy.
AB  - Intermolecular nuclear Overhauser effects (NOEs) between the integral outer
      membrane protein OmpX from Escherichia coli and small bicelles of dihexanoyl
      phosphatidylcholine (DHPC) and dimyristoyl phosphatidylcholine (DMPC) give
      insights into protein-lipid interactions. Intermolecular NOEs between hydrophobic
      tails of lipid and protein in the bicelles cover the surface area of OmpX forming
      a continuous cylindric jacket of approximately 2.7 nm in height. These NOEs
      originate only from DMPC molecules, and no NOEs from DHPC are observed. Further,
      these NOEs are mainly from methylene groups of the hydrophobic tails of DMPC, and
      only a handful of NOEs arise from methyl groups of the hydrophobic tails. The
      observed contacts indicate that the hydrophobic tails of DMPC are oriented
      parallel to the surface of OmpX and thus DMPC molecules form a bilayer in the
      vicinity of the protein. Thus, a bilayer exists in the small bicelles not only in
      the absence of but also in the presence of a membrane protein. In addition, the
      number of NOEs between the polar head groups of lipid molecules and protein is
      increased in the bicelles compared with those in micelles. This observation may
      be due to the closely packed head groups of the bilayer. Moreover, irregularity
      of hydrophobic interactions in the middle of the bilayer environment was
      observed. This observation together with the interactions between polar head
      groups and proteins gives a possible rationale for structural and functional
      differences of membrane proteins solubilized in micelles and in bilayer systems
      and hints at structural differences between protein-free and protein-loaded
      bilayers.

PMID- 18817395
TI  - Polymeric PARACEST agents for enhancing MRI contrast sensitivity.
AB  - Linear polymers of PARACEST agents were prepared by using classical free radical
      chain polymerization conditions. The Eu3+-polymers exhibited similar intermediate
      to-slow water exchange and CEST characteristics as the Eu3+-monomers. This
      provided an avenue to lower the detection limit of these imaging agents
      substantially and makes them potentially useful as MRI sensors for molecular
      imaging.

PMID- 18817396
TI  - Struture stability and compressibility of iron-based superconductor
      Nd(O0.88F0.12)FeAs under high pressure.
AB  - The high-pressure angle-dispersive X-ray diffraction experiments on the iron
      based superconductor Nd(O0.88F0.12)FeAs were performed up to 32.7 GPa at room
      temperature. An isostructural phase transition starts at approximately 10 GPa.
      When pressure is higher than 13.5 GPa, Nd(O0.88F0.12)FeAs completely transforms
      to a high-pressure phase, which remains the same tetragonal structure with a
      larger a-axis and smaller c-axis than those of the low-pressure phase. The
      ambient conditions isothermal bulk moduli B0 are derived as 102(2) and 245(9) GPa
      for the low-pressure phase and high-pressure phase, respectively. The structure
      analysis based on the Rietveld refinement methods shows the difference of
      pressure dependence of the Fe-As and Nd-(O, F) bonding distances, as well as As
      Fe-As and Nd-(O, F)-Nd angles between the low-pressure phase and high-pressure
      phase.

PMID- 18817397
TI  - Mechanistic studies on the reductive cyclooligomerisation of CO by U(III) mixed
      sandwich complexes; the molecular structure of [(U(eta-C8H6{Si(i)Pr3-1,4}2)(eta
      Cp*)]2(mu-eta1:eta1-C2O2).
AB  - The stoichiometric reaction of 1 equiv of CO with [(U(eta-C8H6{SiiPr3-1,4}2)(eta
      Cp*)] affords the linear diuranium ynediolate complex [(U(eta-C8H6{SiiPr3
      1,4}2)(eta-Cp*)]2(mu-eta1:eta1-C2O2) which does not react with further CO to give
      the deltate derivative [(U(eta-C8H6{SiiPr3-1,4}2)(eta-Cp*)]2(mu-eta1:eta2-C3O3).
      Spectroscopic and computational studies suggest a plausible mechanism for the
      formation of the deltate complex, in which a "zig-zag" diuranium ynediolate
      species is the key intermediate.

PMID- 18817398
TI  - Synthesis and reactions of a stable 1,2-diaryl-1,2-dibromodisilene: a precursor
      for substituted disilenes and a 1,2-diaryldisilyne.
AB  - Synthesis and isolation of the stable diaryldibromodisilene, Bbt(Br)SiSi(Br)Bbt,
      has been accomplished for the first time. The dibromodisilene underwent
      substitution reactions with organometallic reagents on the low-coordinated
      silicon atom to afford the corresponding substituted disilenes. Furthermore, the
      reaction of 1 with t-BuLi afforded the corresponding 1,2-diaryldisilyne,
      BbtSi[triple bond]SiBbt, the characters of which were revealed by spectroscopic
      and crystallographic analyses.

PMID- 18817399
TI  - Molecular recognition of chiral conformers: a rotational study of the dimers of
      glycidol.
AB  - Two homochiral dimers of glycidol, deriving from two different conformers, have
      been characterized by rotational spectroscopy in a supersonic expansion.

PMID- 18817400
TI  - Asymmetric Mukaiyama aldol reaction of nonactivated ketones catalyzed by allo
      threonine-derived oxazaborolidinone.
AB  - Asymmetric Mukaiyama aldol reaction of nonactivated ketones is realized for the
      first time by using an oxazaborolidinone catalyst derived from O-benzoyl-N-tosyl
      allo-threonine. By employing a dimethylsilyl ketene S,O-acetal as a nucleophile,
      a variety of acetophenone derivatives afford the corresponding tertiary beta
      hydroxy carbonyl compounds with high enantioselectivity up to 98% ee.

PMID- 18817401
TI  - Highly efficient route for enantioselective preparation of chlorohydrins via
      dynamic kinetic resolution.
AB  - Dynamic kinetic resolution (DKR) of various aromatic chlorohydrins with the use
      of Pseudomonas cepacia lipase (PS-C "Amano" II) and ruthenium catalyst 1 afforded
      chlorohydrin acetates in high yields and high enantiomeric excesses. These
      optically pure chlorohydrin acetates are useful synthetic intermediates and can
      be transformed to a range of important chiral compounds.

PMID- 18817402
TI  - Iterative synthesis of 1,3,5-polyphenylene dendrons via C-H activation.
AB  - An iterative synthesis of 1,3,5-polyphenylene dendrons via C-H activation/Suzuki
      Miyaura coupling up to a third generation dendron is described. C-H bonds at the
      focal points of the dendrons are selectively borylated via iridium-catalyzed
      borylation, eliminating the need for reactive protecting groups. Sequential
      additions of low catalyst loadings efficiently borylate higher-generation
      dendrons, whereas higher initial catalyst loadings are less efficient.

PMID- 18817403
TI  - Total syntheses of racemic, natural (-) and unnatural (+) glyceollin I.
AB  - The first total syntheses of racemic glyceollin I and its enantiomers are
      described. A Wittig approach was utilized as an entry to the appropriately
      substituted isoflav-3-ene so that an osmium tetroxide mediated asymmetric
      dihydroxylation could be deployed for stereospecific introduction of the 6a
      hydroxy group. While using triphenylphosphine hydrobromide, a novel method was
      found for gently removing MOM from protected phenolic hydroxyl groups present
      within sensitive systems.

PMID- 18817404
TI  - Stereochemical study of chiral tautomeric flavorous furanones by vibrational
      circular dichroism.
AB  - 2-Substituted-3(2H)-furanone derivatives are industrially significant aroma
      compounds possessing a unique keto-enol tautomeric feature causing their
      racemization. Absolute configurations of two flavorous furanones, which have
      remained unclear for the past 40 years since their discovery, were clarified by
      the vibrational circular dichroism technique as well as chemical relay reactions.
      Odor evaluation of each enantiomer revealed relationships between their
      configurations and their odor activities.

PMID- 18817405
TI  - Two-step, one-pot Ni-catalyzed neopentylglycolborylation and complementary Pd/Ni
      catalyzed cross-coupling with aryl halides, mesylates, and tosylates.
AB  - Two-step, one-pot neopentylglycolborylation of aryl iodides and bromides
      catalyzed by NiCl2(dppe) and NiCl2(dppp) is reported. Electron-rich and electron
      deficient aryl neopentylglycolboronates were efficiently cross-coupled with aryl
      iodides, bromides, chlorides, mesylates, and tosylates by exploiting
      complementary Pd/Ni and Ni/Ni catalysis. The borylation route was further
      extended to a three-step, one-pot synthesis of biaryls via in situ Ni-catalyzed
      borylation and Pd-mediated cross-coupling.

PMID- 18817406
TI  - Axial 4,4',6,6'-tetrakis-trifluoromethyl-biphenyl-2,2'-diamine (TF-BIPHAM):
      resolution and applications in asymmetric hydrogenation.
AB  - The racemic TF-BIPHAM was resolved for the first time, and the effectiveness of
      the resolved diamine was demonstrated by highly enantioselective hydrogenation of
      alpha-aryl enamides and alpha-dehydroamino acid esters using readily accessible
      bis(aminophosphine) ligands.

PMID- 18817407
TI  - Synthesis of delta-tributylstannyl-alpha,beta,gamma,delta-unsaturated aldehydes
      from pyridines.
AB  - Zincke aldehydes, which are readily available from the ring-opening reaction of
      pyridinium salts, are easily converted into delta-tributylstannyl
      alpha,beta,gamma,delta-unsaturated aldehydes (stannyldienals) by the action of
      tributylstannyllithium. This reaction appears to proceed via 1,6-stannyllithium
      addition/elimination of lithium dialkylamide. Several stannyldienals of
      significant utility for the synthesis of polyene natural products have been made
      by this route, which proceeds in modest yields, but is successful on multigram
      scale using inexpensive reagents. Simple stannylenals and stannylenones are
      similarly available from the corresponding vinylogous amides.

PMID- 18817408
TI  - Involvement of Ca2+ in the inhibition by crocetin of platelet activity and
      thrombosis formation.
AB  - Crocetin, a unique carotenoid with potent antioxidative and anti-inflammatory
      activities, is a major ingredient of saffron used as an important spice and food
      colorant in various parts of the world. In the present study, the effects of
      crocetin on platelet activity and thrombosis formation were systematically
      investigated. Crocetin showed a dose-dependent inhibition of platelet aggregation
      induced by ADP, collagen, but not by arachidonic acid (AA). Crocetin
      significantly attenuated dense granule release, while neither platelets adhesion
      to collagen nor cyclic AMP level was altered by crocetin. Pretreatment with
      crocetin was confirmed to partially inhibit Ca (2+) mobilization via reducing
      both intracellular Ca (2+) release and extracellular Ca (2+) influx. Besides
      that, crocetin prolonged the occlusive time in electrical stimulation-induced
      carotid arterial thrombosis. These findings suggest that the favorable impacts of
      crocetin on platelet activity and thrombosis formation may be related to the
      inhibition of Ca (2+) elevation in stimulated platelets.

PMID- 18817409
TI  - Lipophilic extracts from banana fruit residues: a source of valuable
      phytosterols.
AB  - The chemical composition of the lipophilic extracts of unripe pulp and peel of
      banana fruit 'Dwarf Cavendish' was studied by gas chromatography-mass
      spectrometry. Fatty acids, sterols, and steryl esters are the major families of
      lipophilic components present in banana tissues, followed by diacylglycerols,
      steryl glucosides, long chain fatty alcohols, and aromatic compounds. Fatty acids
      are more abundant in the banana pulp (29-90% of the total amount of lipophilic
      extract), with linoleic, linolenic, and oleic acids as the major compounds of
      this family. In banana peel, sterols represent about 49-71% of the lipophilic
      extract with two triterpenic ketones (31-norcyclolaudenone and cycloeucalenone)
      as the major components. The detection of high amounts of steryl esters (469
      24405 mg/kg) and diacylglycerols (119-878 mg/kg), mainly present in the banana
      peel extract, explains the increase in the abundance of fatty acids and sterols
      after alkaline hydrolysis. Several steryl glucosides were also found in
      significative amounts (273-888 mg/kg), particularly in banana pulp (888 mg/kg).
      The high content of sterols (and their derivatives) in the 'Dwarf Cavendish'
      fruit can open new strategies for the valorization of the banana residues as a
      potential source of high-value phytochemicals with nutraceutical and functional
      food additive applications.

PMID- 18817411
TI  - Nondestructive measurement of fresh tomato lycopene content and other
      physicochemical characteristics using visible-NIR spectroscopy.
AB  - Measurement of fresh tomato fruit overall quality, and particularly lycopene
      content, is challenging in the context of high-volume production. An experiment
      was conducted to simultaneously measure various quality parameters of tomato in a
      nondestructive manner using vis-NIR reflectance spectroscopy and chemometrics.
      The sampling set included different cultivars that are obtainable from both
      retailers' shelves and two greenhouse producers. Results indicate that lycopene
      content was accurately predicted [r(2) = 0.98; root mean square error of cross
      validation (RMSECV) = 3.15 mg/kg], along with color variables such as Hunter a
      (r(2) = 0.98), L, and b (r(2) = 0.92). Tomato color index (TCI) was better
      predicted (r(2) = 0.96) than the a/ b ratio (r(2) = 0.89). Firmness prediction,
      with an r(2) of 0.75, is comparable to what is reported in the literature for
      other fruits and may have a practical interest. Prediction of internal quality
      such as pH, soluble solids, titratable acidity, and electrical conductivity was
      less accurate, partly due to a low variability of these parameters among samples.
      Predictions were robust with regard to cultivars, except for pink variety tomato.
      The 400-1000 nm range gave results almost as accurate as the 400-1500 nm range.

PMID- 18817410
TI  - Stability evaluation of selected polyphenols and triterpene glycosides in black
      cohosh.
AB  - Black cohosh ( Actaea racemosa L., syn. Cimicifuga racemosa L.) is rich in both
      triterpene glycosides and polyphenols, which have various biological activities
      that may be important to its medical use. To evaluate the stability of the
      polyphenolic constituents and triterpene glycosides of black cohosh, experiments
      were conducted using three sample types: plant material, extracts of black
      cohosh, and encapsulated commercial extract. The samples were stored at various
      temperatures and humidity conditions. Three triterpene glycosides and six major
      polyphenols in black cohosh were quantitatively measured with an HPLC-PDA method
      at 0, 3, 6, and 9 weeks. The triterpene glycosides were stable at the tested
      conditions, whereas the polyphenols were stable only at room temperature and low
      humidity and not stable at higher temperature and/or humidity due to hydrolysis
      and/or oxidation. The rate of compound decomposition depended upon the chemical
      structure of the individual polyphenols. Polyphenols in the extracts decomposed
      more readily than those in plant material.

PMID- 18817412
TI  - Structure determination of 3-O-caffeoyl-epi-gamma-quinide, an orphan bitter
      lactone in roasted coffee.
AB  - Recent investigations on the bitterness of coffee as well as 5- O-caffeoyl quinic
      acid roasting mixtures indicated the existence of another, yet unknown, bitter
      lactone besides the previously identified bitter compounds 5- O-caffeoyl- muco
      gamma-quinide, 3- O-caffeoyl-gamma-quinide, 4- O-caffeoyl- muco-gamma-quinide, 5-
      O-caffeoyl- epi-delta-quinide, and 4- O-caffeoyl-gamma-quinide. In the present
      study, this orphan bitter lactone was isolated from the reaction products
      generated by dry heating of 5- O-caffeoylquinic acid model, and its structure was
      determined as the previously unreported 3- O-caffeoyl- epi-gamma-quinide by means
      of liquid chromatography-mass spectrometry (LC-MS) and one-/two-dimensional NMR
      experiments. The occurrence of this bitter lactone, exhibiting a low bitter
      recognition threshold of 58 micromol/L, in coffee beverages could be confirmed by
      LC-MS/MS (negative electrospray ionization) operating in the multiple reaction
      monitoring mode.

PMID- 18817413
TI  - Field aging of insecticides after repeated application to a northern Thailand
      ultisol.
AB  - Field aging immobilizes pollutants and reduces their toxicity, but it also boosts
      their accumulation and holds the risk of future release. We investigated the
      aging of six insecticides (water solubilities: 0.33 mg L (-1)-completely
      miscible) applied five times (10-day intervals) to a tropical fruit orchard under
      natural weather conditions. After sequential extractions of soil samples with
      0.01 M CaCl 2, methanol (MeOH), and acetone/ethylacetate/water (AEW), a
      conventional ( K OC(app) = [ c(MeOH) + c(AEW)]/ c(CaCl 2), normalized to soil
      organic carbon) and a newly introduced distribution ratio (MAR = MeOH/AEW ratio;
      c(MeOH)/ c(AEW)) were calculated. Field half-lives of the insecticides correlated
      with K OC(app) but not with MAR, which might reflect that dissipation was
      significantly affected by abiotic processes. The extent of aging was related to
      hydrophobicity of the compounds and most pronounced for endosulfan (3-fold
      increase in K OC(app) within 84 days). For dimethoate, this increase was even
      steeper (5- to 10-fold within 10 days), which was, however, mostly caused by
      dissipation from labile pools rather than by aging. The K OC(app) of chlorpyrifos
      remained constant, but a significant decrease in MAR ( r = -0.78) revealed that
      sorption strength increased nevertheless. Results for malathion were ambiguous.
      Within the time frame of our study, neither K OC(app) nor MAR gave evidence for
      the aging of mevinphos. The different dynamics of K OC(app) and MAR for the six
      insecticides studied indicate that different aging mechanisms or rates, or both
      control the fate of the individual insecticides, which can potentially be
      revealed by sequential exctraction procedures.

PMID- 18817414
TI  - Application of the reactive lysine procedure to estimate lysine digestibility in
      distillers dried grains with solubles fed to growing pigs.
AB  - Two experiments were conducted to measure the reactive Lys concentration in corn
      distillers dried grains with solubles (DDGS). In expt 1, reactive Lys was
      measured in 33 sources of DDGS using two procedures: the homoarginine procedure
      and the furosine procedure. The concentration of reactive Lys in DDGS was then
      correlated with the concentration of standardized ileal digestible (SID) Lys in
      DDGS fed to growing pigs. In expt 2, a factorial experiment was conducted using
      four ratios of condensed distillers solubles (CDS) and wet distillers grain
      (WDG). The ratios (wt/wt) of CDS to WDG were 0:100, 20:80, 40:60, and 100:0, and
      four subsamples from each combination were freeze-dried or oven-dried at 50, 75,
      or 100 degrees C. The dried samples were designated DDG, DDGS 20, DDGS 40, and
      CDS, respectively. All subsamples were analyzed for total Lys and for reactive
      Lys using the homoarginine procedure. Results of expt 1 showed that only 74.1% of
      total Lys was reactive if measured by the homoarginine procedure and 83.5% was
      reactive if measured by the furosine procedure. The concentration of SID Lys in
      DDGS was correlated with the concentration of reactive Lys measured by the
      homoarginine procedure ( r (2) = 0.70, P < 0.05) and by the furosine procedure (
      r (2) = 0.66, P < 0.05). In expt 2, the concentrations of total Lys and reactive
      Lys were reduced ( P < 0.05) when addition of CDS or drying temperature of the
      samples was increased, but the reduction was greater ( P < 0.05) when both CDS
      addition and drying temperature were increased at the same time. After oven
      drying at 100 degrees C, 75.7% of total Lys was reactive in DDG, but only 27.6
      and 10.2% were reactive in DDGS 20 and DDGS 40, respectively. In conclusion,
      reactive Lys is correlated with the concentration of SID Lys in DDGS, and
      addition of CDS exacerbates the negative effects of heating on the concentration
      of total Lys and reactive Lys in DDGS.

PMID- 18817415
TI  - Peroxyl radical scavenging capacity, polyphenolics, and lipophilic antioxidant
      profiles of mulberry fruits cultivated in southern China.
AB  - Twenty-seven cultivars of mulberry fruits ( Morus atropurpurea Roxb) were
      analyzed for their total phenolic content, total anthocyanin content, and peroxyl
      radical scavenging capacities. The proanthocyanidin contents of the fruit were
      also quantified using 4-dimethylamino-cinnamaldehyde assay, and characterization
      was attempted using electrospray ionization mass spectra. The phenolic compounds
      of mulberry fruits were characterized using HPLC with ESI-MS and diode array
      detection. Results showed that the content of mulberry fruits varied with
      different cultivars with total phenolic content, total anthocyanin content, total
      proanthocyanidin content, and peroxyl radical scavenging capacities ranging from
      0.060-0.244, 0.001-0.056, 0.001-0.015, and 0.301-1.728, respectively. Good
      correlations were observed among the phenolic, anthocyanin, and proanthocyanidin
      contents and the radical scavenging capacities of mulberry fruits. Mulberry
      fruits were found to contain low amount of proanthocyanidins. The high total
      phenolic content of mulberry fruits were mainly contributed by anthocyanins,
      rutin, and chlorogenic acids. The lipid soluble antioxidants are profiled by an
      HPLC method developed in-house, and the results of selected mulberry fruits
      revealed significant amounts of lutein and delta- and gamma-tocopherols but low
      alpha-tocopherol. Our results provide useful antioxidant nutritional information
      of a mulberry cultivar that has potential for large scale plantations.

PMID- 18817416
TI  - A heavy-atom isotope effect and kinetic investigation of the hydrolysis of
      semicarbazide by urease from jack bean (Canavalia ensiformis).
AB  - A kinetic investigation of the hydrolysis of semicarbazide by urease gives a
      relatively flat log V/ K versus pH plot between pH 5 and 8. A log V m versus pH
      plot shows a shift of the optimum V m toward lower pH when compared to urea.
      These results are explained in terms of the binding of the outer N of the NHNH 2
      group in semicarbazide to an active site residue with a relatively low p K a (
      approximately 6). Heavy-atom isotope effects for both leaving groups have been
      determined. For the NHNH 2 side, (15) k obs = 1.0045, whereas for the NH 2 side,
      (15) k obs = 1.0010. This is evidence that the NHNH 2 group leaves prior to the
      NH 2 group. Using previously published data from the urease-catalyzed hydrolysis
      of formamide, the commitment factors for semicarbazide and urea hydrolysis are
      estimated to be 2.7 and 1.2, respectively. The carbonyl-C isotope effect ( (13) k
      obs) equals 1.0357, which is consistent with the transition state occurring
      during either formation or breakdown of the tetrahedral intermediate.

PMID- 18817417
TI  - Integrin binding immunoglobulin type filamin domains have variable stability.
AB  - Filamin, a large modular protein composed mainly of many immunoglobulin-like
      domains, is a potent cross-linker of actin filaments. The region containing
      immunoglobulin type modules 19-21 makes up the binding site for the cytoplasmic
      tails of the integrin adhesion receptors. Here we investigate the stability of
      the Ig-like filamin domains using NMR studies over a range of pH and temperature.
      We show that the 21st Ig-like module (FLNa21) is partly unfolded even under
      physiological conditions and when attached to FLNa20. It is, however, appreciably
      stabilized upon binding to integrins. FLNa21 is noticeably less stable than
      neighboring homologous modules, such as FLNa19 and FLNa17. This variability in
      stability could be related to the known sensitivity of filamin to cell-mediated
      mechanical forces.

PMID- 18817418
TI  - Kinetic isotope effects on aromatic and benzylic hydroxylation by Chromobacterium
      violaceum phenylalanine hydroxylase as probes of chemical mechanism and
      reactivity.
AB  - Phenylalanine hydroxylase from Chromobacterium violaceum (CvPheH) is a non-heme
      iron monooxygenase that catalyzes the hydroxylation of phenylalanine to tyrosine.
      In this study, we used deuterium kinetic isotope effects to probe the chemical
      mechanisms of aromatic and benzylic hydroxylation to compare the reactivities of
      bacterial and eukaryotic aromatic amino acid hydroxylases. The (D) k cat value
      for the reaction of CvPheH with [(2)H 5]phenylalanine is 1.2 with 6
      methyltetrahydropterin and 1.4 with 6,7-dimethyltetrahydropterin. With the mutant
      enzyme I234D, the (D) k cat value decreases to 0.9 with the latter pterin; this
      is likely to be the intrinsic effect for addition of oxygen to the amino acid.
      The isotope effect on the subsequent tautomerization of a dienone intermediate
      was determined to be 5.1 by measuring the retention of deuterium in tyrosine
      produced from partially deuterated phenylalanine; this large isotope effect is
      responsible for the normal effect on k cat. The isotope effect for hydroxylation
      of the methyl group of 4-CH 3-phenylalanine, obtained from the partitioning of
      benzylic and aromatic hydroxylation products, is 10. The temperature dependence
      of this isotope effect establishes the contribution of hydrogen tunneling to
      benzylic hydroxylation by this enzyme. The results presented here provide
      evidence that the reactivities of the prokaryotic and eukaryotic hydroxylases are
      similar and further define the reactivity of the iron center for the family of
      aromatic amino acid hydroxylases.

PMID- 18817419
TI  - Investigation of the role of surface chemistry and accessibility of cadmium
      adsorption sites on open-surface carbonaceous materials.
AB  - Carbon nanotubes fabricated by the dc arc discharge method (ADCNTs) and chemical
      vapor deposition method (CVDCNTs) were oxidized with concentrated HNO 3 to modify
      their surface chemistry. The materials were characterized using SEM, TEM, FTIR,
      XPS, potentiometric titration, and nitrogen adsorption. The initial and oxidized
      materials were used as adsorbents of cadmium from aqueous solutions with
      different pH. Langmuir and Freundlich adsorption models were applied to fit the
      isotherm data, and both models fit the experimental data very well. The acid
      oxidation resulted in an increase in the number of oxygen-containing groups
      without drastic changes in the texture of the adsorbents. Although the small
      volume of micropores is present, the nanotube structure can be considered as
      nonporous. The lack of developed microporosity in carbonaceous materials
      eliminates the inner surface diffusion problems and makes the vast majority of
      surface groups available for adsorption of cadmium. The availability of these
      centers depends on the pH of the solution, which controls the protonation level.
      In spite of the fact that the pH of the solution affects the speciation of
      cadmium to some degree, the surface chemistry is the predominant force for
      adsorption at the pH range adopted in the present study, while the texture of
      materials also affects the nanotube's cadmium-adsorbing performance.

PMID- 18817420
TI  - Shear induced relaxation of polymer micelles at the solid-liquid interface.
AB  - A 20% aqueous solution of (ethylene oxide) 99-(propylene oxide) 65-(ethylene
      oxide) 99, F127, was investigated by combining rheology in a cone/plate-geometry
      and surface-sensitive grazing incident neutron scattering. The crystalline
      structure formed by the polymer micelles becomes less pronounced for low shear
      rates, but correlations increase for higher shear rates. After stopping shear a
      slow relaxation of the micelles is found in the vicinity (50 mum thick layer) of
      a hydrophilic silicon wall (strong micelle-wall interaction), while a fast
      relaxation is observed in the boundary layer against the hydrophobic silicon wall
      (weak micelle-wall interaction). The results show that in the vicinity of the
      interface wall-particle interactions compete heavily with the shear force acting
      on the liquid.

PMID- 18817421
TI  - A facile, water-based synthesis of highly branched nanostructures of silver.
AB  - We report a facile and environmentally friendly method of preparing highly
      branched silver nanostructures. By reducing AgNO 3 with l-ascorbic acid in an
      aqueous solution, silver particles having a coral-like morphology were formed in
      a few minutes. A mechanistic study of the growth process revealed that the silver
      branches grew from a bulbous seed formed through aggregation, and that by
      changing the concentrations of the reagents, the degree of particle branching
      could be altered. With their potentially high surface areas, these branched
      structures could find use as catalysts or as substrates for surface-enhanced
      Raman scattering applications.

PMID- 18817422
TI  - Kinetics of enzyme attack on substrates covalently attached to solid surfaces:
      influence of spacer chain length, immobilized substrate surface concentration and
      surface charge.
AB  - The use of alpha-chymotrypsin to cleave covalently bound N-acetyl- l-tryptophan
      (Ac-Trp-OH) from the surfaces of aminopropylated controlled pore glass (CPG) and
      the polymer PEGA 1,900 was investigated. Oligoglycine spacer chains were used to
      present the covalently attached Ac-Trp-OH substrate to the aqueous enzyme. In the
      absence of the oligoglycine spacer chain, the rate of release was relatively
      slow, especially from the PEGA 1,900. These slow rates reflect the position of
      the amino group to which Ac-Trp-OH is covalently attached. On the glass there was
      a clear optimum with a chain of four glycine residues. For PEGA 1,900 there is no
      real apparent change beyond two glycine residues. The decline in rate beyond
      these optima are a possible result of changes in oligoglycine structure.
      Comparing different surface loadings of bound substrate the rate of release of Ac
      Trp-OH from CPG with a pore diameter of 1,200 A was optimal when using 83% of the
      maximum that can be coupled, then fell again at higher loading. The rate of Ac
      Trp-OH release from CPG was the same for surface coverages of 0.4 and 1.0. The
      introduction of permanent surface charges on CPG 1,200 exhibits a distinct
      influence on enzymatic cleavage with an increase in the rate of biocatalysis at
      the surface. Optimal presentation of covalently immobilized substrate on
      different supports by use of appropriate linkers leads to favorable biocatalysis
      from the support.

PMID- 18817423
TI  - Methane interactions with polyaniline/butylmethylimidazolium camphorsulfonate
      ionic liquid composite.
AB  - In our previous report, a polyaniline (PAn) and ionic liquid
      butylmethylimidazolium camphorsulfonate (BMICS) composite was used as a methane
      sensing material which significantly increased the sensitivity for methane
      detection using quartz crystal microbalance (QCM) transducers. In this paper, we
      focus on the interactions within the PAn/BMICS composite and between the
      composite and methane. UV-vis and Fourier transform infrared (FTIR) spectroscopic
      results indicated that the anion of BMICS, camphorsulfonate, could form hydrogen
      bonds with the "nitrogen" sites of protic acid doped PAn. These hydrogen bonds
      align the camphorsulfonate anions in a comblike manner along the PAn backbone and
      therefore enhance the long-range pi-orbital conjugation of PAn. Methane molecules
      absorbed into the PAn/BMICS may sit in the "space" between the aligned anions and
      cations of BMICS. By measuring the methane absorption in PAn/BMICS at a
      temperature range of 25-65 degrees C, the entropy and enthalpy of dissolution
      were obtained following the van't Hoff equation. They are -163.2 +/- 30.1 J/mol.K
      and -50.5 +/- 8.7 kJ/mol, respectively, which are relatively higher than those in
      pure BMICS and in PAn only. These thermodynamic parameters further support that
      the absorbed methane molecules might exist in PAn/BMICS in a relatively ordered
      manner. Molecular mechanics simulation results agree with the spectroscopic and
      thermodynamic results.

PMID- 18817424
TI  - Formation of ternary poly(acrylic acid)-surfactant-Cu2+ complexes in aqueous
      solution: quenching of pyrene fluorescence and pH-controlled "on-off" emitting
      properties.
AB  - The formation of binary and ternary complexes of poly(acrylic acid) (PAA) with N,
      N, N, N-dodecyltrimethylammonium chloride (DTAC) and/or Cu (2+) ions is
      investigated in dilute aqueous solution through turbidimetry, viscometry, and
      pyrene fluorescence probing. It is shown that the PAA-DTAC and PAA-Cu (2+)
      complexation as well as the formation of ternary PAA-DTAC-Cu (2+) complexes are
      controlled from the pH of the aqueous solution. A pronounced quenching of the
      emission of pyrene is observed when ternary PAA-DTAC-Cu (2+) complexes are
      formed, as a result of the close proximity of Cu (2+) ions (complexed along the
      polymer chain) and the probe (solubilized in the hydrophobic mixed polymer
      surfactant aggregates), as indicated from the corresponding Stern-Volmer plots. A
      significant quenching is also observed when poly(sodium styrene sulfonate) is
      used instead of PAA, indicating that electrostatically bound Cu (2+) ions are
      still effective quenchers of the emission of the probes under similar conditions.
      Finally, it is demonstrated that the formation-deformation of the ternary PAA
      DTAC-Cu (2+) complexes upon changing pH may act as a pH-controlled "on-off"
      switch of the emission of pyrene in aqueous solution.

PMID- 18817425
TI  - Thermolysis of polymeric [Ru(CO)4]infinity to metallic ruthenium: molecular shape
      of the precursor affects the nanoparticle shape.
AB  - Pyrolysis of the organometallic polymer [Ru(CO) 4] infinity affords metallic
      ruthenium nanofibers. The molecular structure, especially the presence of metal
      metal bonds, appears to direct the aggregation of the metal atom chains upon loss
      of the carbonyl ligands.

PMID- 18817426
TI  - Microwave, photo- and thermally responsive PNIPAm-gold nanoparticle microgels.
AB  - Microwave-, photo- and thermo-responsive polymer microgels that range in size
      from 500 to 800 microm and are swollen with water were prepared by a novel
      microarray technique. We used a liquid-liquid dispersion technique in a system of
      three immiscible liquids to prepare hybrid PNIPAm- co-AM core-shell capsules
      loaded with AuNPs. The spontaneous encapsulation is a result of the formation of
      double oil-in-water-in-oil (o/w/o) emulsion. It is facilitated by adjusting the
      balance of the interfacial tensions between the aqueous phase (in which a water
      soluble drug may be dissolved), the monomer phase and the continuous phase. The
      water-in-oil (w/o) droplets containing 26 wt% NIPAm and Am monomers, 0.1 wt%
      Tween-80 surfactant, FITC fluorescent dye and colloidal gold nanoparticles
      spontaneously developed a core-shell morphology that was fixed by in situ
      photopolymerization. The results demonstrate new reversibly swelling and
      deswelling AuNP/PNIPAm hybrid core-shell microcapsules and microgels that can be
      actuated by visible light and/or microwave radiation (<or=1,250 nm) and/or
      temperature. This is the first study to demonstrate that incorporating AuNPs
      speeds up the response kinetics of PNIPAm, and hence enhances the sensitivity to
      external stimuli of PNIPAm. These microgels can have potential applications for
      microfluidic switches or microactuators, photosensors, and various nanomedicine
      applications in controlled delivery and release.

PMID- 18817427
TI  - Photoresponsive surfaces with two independent wavelength-selective functional
      levels.
AB  - Two photoremovable protecting groups, namely, nitroveratryloxycarbonyl (NVo) and
      diethylamino-coumarin-4-yl (DEACM), have been tested for wavelength-selective,
      independent removal. The chromophores were attached to the amine group of
      aminopropyltriethoxysilane and used for the modification of silica surfaces. A
      photolytic experiment on the photosensitive layers allowed us to identify the
      irradiation conditions for the selective cleavage of the chromophores. UV
      measurements revealed that the photolabile DEACM group can be cleaved off with UV
      light at 412 nm without damaging the NVo group. The NVo group could then be
      removed at 365 nm. Masked irradiation of substrates modified with a 1:1 molar
      mixture of both silanes allowed the generation of bifunctional patterns after the
      selective cleavage of DEACM and NVo in a sequential irradiation process. The
      deprotection reaction was confirmed by coupling two different fluorescent dyes to
      the liberated amine groups. The expected two-color pattern could be observed by
      fluorescence microscopy.

PMID- 18817428
TI  - Selective photothermal therapy for mixed cancer cells using aptamer-conjugated
      nanorods.
AB  - Safe and effective photothermal therapy depends on efficient delivery of heat for
      killing cells and molecular specificity for targeting cells. To address these
      requirements, we have designed an aptamer-based nanostructure which combines the
      high absorption efficiency of Au-Ag nanorods with the target specificity of
      molecular aptamers, a combination resulting in the development of an efficient
      and selective therapeutic agent for targeted cancer cell photothermal
      destruction. Most nanomaterials, such as gold nanoshells or nanorods (NRs),
      require a relatively high power of laser irradiation (1 x 10 (5)-1 x 10 (10) W/m
      (2)). In contrast, the high absorption characteristic of our Au-Ag NRs requires
      only 8.5 x 10 (4) W/m (2) laser exposure to induce 93 (+/-11)% cell death of NR
      aptamer-labeled cells. Aptamers, the second component of the nanostructure, are
      generated from a cell-SELEX (systematic evolution of ligands by exponential
      enrichment) process and can be easily selected for specific recognition of
      individual tumor cell types without prior knowledge of the biomarkers for the
      cell. When tested with both cell suspensions and artificial solid tumor samples,
      these aptamer conjugates were shown to have excellent hyperthermia efficiency and
      selectivity. Under a specific laser intensity and duration of laser exposure,
      about 50 (+/-1)% of target (CEM) cells were severely damaged, while more than 87
      (+/-1)% of control (NB-4) cells remained intact in a suspension cell mixture.
      These results indicate that the Au-Ag nanorod combination offers selective and
      efficient photothermal killing of targeted tumor cells, thus satisfying the two
      key challenges noted above. Consequently, for future in vivo application, it is
      fully anticipated that the tumor tissue will be selectively destroyed at laser
      energies which will not harm the surrounding normal tissue.

PMID- 18817429
TI  - The collaboratory for MS3D: a new cyberinfrastructure for the structural
      elucidation of biological macromolecules and their assemblies using mass
      spectrometry-based approaches.
AB  - Modern biomedical research is evolving with the rapid growth of diverse data
      types, biophysical characterization methods, computational tools and extensive
      collaboration among researchers spanning various communities and having
      complementary backgrounds and expertise. Collaborating researchers are
      increasingly dependent on shared data and tools made available by other
      investigators with common interests, thus forming communities that transcend the
      traditional boundaries of the single research laboratory or institution.
      Barriers, however, remain to the formation of these virtual communities, usually
      due to the steep learning curve associated with becoming familiar with new tools,
      or with the difficulties associated with transferring data between tools.
      Recognizing the need for shared reference data and analysis tools, we are
      developing an integrated knowledge environment that supports productive
      interactions among researchers. Here we report on our current collaborative
      environment, which focuses on bringing together structural biologists working in
      the area of mass spectrometric based methods for the analysis of tertiary and
      quaternary macromolecular structures (MS3D) called the Collaboratory for MS3D (C
      MS3D). C-MS3D is a Web-portal designed to provide collaborators with a shared
      work environment that integrates data storage and management with data analysis
      tools. Files are stored and archived along with pertinent meta data in such a way
      as to allow file handling to be tracked (data provenance) and data files to be
      searched using keywords and modification dates. While at this time the portal is
      designed around a specific application, the shared work environment is a general
      approach to building collaborative work groups. The goal of this is to not only
      provide a common data sharing and archiving system, but also to assist in the
      building of new collaborations and to spur the development of new tools and
      technologies.

PMID- 18817430
TI  - Proteomic analysis of oxidative stress-responsive proteins in human pneumocytes:
      insight into the regulation of DJ-1 expression.
AB  - Oxidative injury is believed to play an important role in the pathogenesis of
      lung diseases such as emphysema and lung cancer. We examined the effects of a
      classic reactive oxygen species, H 2O 2, on the hydrogen peroxide response
      proteins (HPRP) in human pneumocytes using comparative two-dimensional gel
      electrophoresis (2DE) and peptide mass fingerprinting. Four HPRP-associated
      proteins (DJ-1, peroxiredoxins [Prxs] I and IV and glyceraldehyde-3-phosphate
      dehydrogenase [GAPDH]) were changed upon exposure to H 2O 2 (1 mM for 24 h). H 2O
      2 exposure increased the acid (oxidized) form and decreased the basic (reduced)
      form of DJ-1 (pI 5.8 and 6.2, respectively), Prx I and IV and GAPDH. Mechanistic
      studies on DJ-1 indicated that the slow recovery of the reduced form was blocked
      by cyclohexamide, suggesting that the recovery was due to new protein synthesis.
      Total DJ-1 expression was decreased by increasing concentrations of H 2O 2. In
      contrast, a more complex mix of oxidants in the form of cigarette smoke extract
      (CSE) dose-dependently increased DJ-1 expression and produced a novel DJ-1
      isoform (p I 5.6). Moreover, DJ-1 expression was higher in the lungs of chronic
      cigarette smokers compared with nonsmokers, a result which resembled the effects
      of CSE in cultured cells. These data indicate that in human pneumocytes, DJ-1
      functions as an antioxidant but that no enzymatic system converts the oxidized to
      the reduced form. Up-regulation of DJ-1 by cigarette smoke may be a compensatory
      mechanism that protects the lung from oxidative stress-related injury.

PMID- 18817431
TI  - Visualization of long human telomere mimics by single-molecule fluorescence
      imaging.
AB  - Study of long single-stranded telomeric DNA is important for a variety of basic
      science and biotechnological applications, yet few methods exist for synthesis
      and visualization of single copies of this DNA in solution at biologically
      relevant length scales necessary for assessment of heterogeneity in its structure
      and behavior. We have synthesized kilobase-long single-stranded human telomere
      mimics in situ by rolling circle replication (RCR) on a microscope coverslip
      surface and visualized individual strands by staining with SYBR Gold. Under
      buffer flow, differential extensibility and varying morphology of these long
      telomere-mimicking DNA sequences were observed at the single-molecule level in
      real time. Using this procedure, we detected striking differences in the
      extensibility of individual RCR products based on the human G-rich telomeric
      sequence in the presence and absence of short, complementary single-stranded
      oligonucleotides. We also apply this new mode of single-stranded DNA
      characterization to probe the interaction of kilobase-length telomere mimics with
      the small-molecule G-quadruplex-binding agent TMPyP4.

PMID- 18817432
TI  - Finer structures of polyelectrolyte multilayers reflected by solution (1)H NMR.
AB  - Water-dispersible polyelectrolyte multilayers (PEM) were obtained by layer-by
      layer assembly of poly(allylamine hydrochloride) (PAH) and poly(sodium 4-styrene
      sulfonate) (PSS) on water-soluble poly(ethylene glycol)- graft-multiwalled carbon
      nanotubes (PEG- g-MWNTs), and their structures were investigated using solution
      (1)H NMR. It was clearly shown that some segments of the adsorbed topmost layers
      formed in layer-by-layer assembly processes are still highly mobile in aqueous
      solution, and these segments are totally compensated by subsequent coatings of
      the oppositely charged layers to form ionically cross-linked polyelectrolyte
      complexes (PEC) layers; it was demonstrated that the ionization behaviors of the
      highly mobile segments of the topmost PAH layers are similar to those in solution
      rather than those in the bulk multilayers at different pH. Furthermore, the
      similarity among the PEM on substrates and the PEC colloids prepared under
      similar conditions in solution was supported by solution (1)H NMR results, and
      the unequal stiochiometry of the cationic group from PAH and the anionic group
      from PSS in the cores of the PEC colloids in solution was identified from
      solution (1)H NMR results using PEG as external references. On the basis of
      these, it is suggested that the PEC layers in PEM formed from coating of the
      adsorbed topmost PAH layers with PSS solution contain excess PSS, and reversely
      those formed from coating of the adsorbed topmost PSS layers with PAH solution
      contain excess PAH. Hence a new description of PEM is put forward that the
      polyelectrolyte multilayers are composed of alternate layers excess either in PSS
      or in PAH.

PMID- 18817433
TI  - The intrinsic stiffness of polyglutamine peptides.
AB  - We have used the method of Trp/Cys contact quenching to measure the rate of
      contact formation in polyglutamine and find it to be a very stiff peptide.
      Separation of observed rates into reaction-limited and diffusion-limited rates
      show that the reaction-limited rates increase (rather than decrease) slightly
      with length between 4 and 16 amino acids. Using Szabo, Schulten, and Schulten
      theory, we have modeled the results with a wormlike chain with excluded volume
      and find the persistence length to be about 13.0 A, much longer than has been
      observed for other random peptides and unfolded proteins. The preferred extended
      conformation of polyglutamine could account for a propensity for expanded
      glutamine stretches to unfold the Huntington's protein and the high propensity to
      aggregate from a disordered monomer.

PMID- 18817434
TI  - Induced smectic phase in mixtures of hyperbranched polyester and liquid crystal
      mesogens.
AB  - The phase diagram of a mixture consisting of hyperbranched polyester (HBPEAc
      COOH) and eutectic nematic liquid crystals (E7) has been established
      experimentally by means of differential scanning calorimetry and polarized
      optical microscopy subjected to prolonged annealing. The observed phase diagram
      is an upper azeotrope, exhibiting the coexistence of nematic + isotropic phase in
      the vicinity of 90 approximately 110 degrees C above the clearing temperature of
      neat E7 (60 degrees C). With decreasing temperature, a focal-conic fan shaped
      texture develops in the composition range of 63 approximately 93 wt % of the
      annealed E7/HBPEAc-COOH blends, suggestive of induced smectic phase in the
      mixture. Wide angle X-ray diffraction (WAXD) technique revealed the existence of
      higher order mesophase(s).

PMID- 18817435
TI  - Density functional theory-based conformational analysis of a phospholipid
      molecule (dimyristoyl phosphatidylcholine).
AB  - The conformational space of the dimyristoyl phosphatidylcholine (DMPC) molecule
      has been studied using density functional theory (DFT), augmented with a damped
      empirical dispersion energy term (DFT-D). Fourteen ground-state isomers have been
      found with total energies within less than 1 kcal/mol. Despite differences in
      combinations of their torsion angles, all these conformers share a common
      geometric profile, which includes a balance of attractive, repulsive, and
      constraint forces between and within specific groups of atoms. The definition of
      this profile fits with most of the structural characteristics deduced from
      measured NMR properties of DMPC solutions. The calculated vibrational spectrum of
      the molecule is in good agreement with experimental data obtained for DMPC
      bilayers. These results support the idea that DMPC molecules preserve their
      individual molecular structures in the various assemblies.

PMID- 18817437
TI  - Insights into melanosomes and melanin from some interesting spatial and temporal
      properties.
AB  - Melanosomes are organelles found in a wide variety of tissues throughout the
      animal kingdom and exhibit a range of different shapes: spheres of up to
      approximately 1 mum diameters and ellipsoids with lengths of up to approximately
      2 mum and varying aspect ratios. The functions of melanosomes include
      photoprotection, mitigation of the effects of reactive oxygen species, and metal
      chelation. The melanosome contains a variety of biological molecules, e.g.,
      proteins and lipids, but the dominant constituent is the pigment melanin, and the
      functions ascribed to melanosomes are uniquely enabled by the chemical properties
      of the melanins they contain. In the past decade, there has been significant
      progress in understanding melanins and their impact on human health. While the
      molecular details of melanin production and how the pigment is organized within
      the melanosome determine its properties and biological functions, the physical
      and chemical properties of the surface of the melanosome are central to their
      range of ascribed functions. Surprisingly, few studies designed to probe this
      biological surface have been reported. In this article, we discuss recent work
      using surface-sensitive analytic, spectroscopic, and imaging techniques to
      examine the structural and chemical properties of many types of natural pigments:
      sepia melanin granules, human and bovine ocular melanosomes, human hair
      melanosomes, and neuromelanin. N 2 adsorption/desorption measurements and atomic
      force microscopy provide novel insights into surface morphology. The chemical
      properties of the melanins present on the surface are revealed by X-ray
      photoelectron spectroscopy and photoemission electron microscopy. These
      technologies are also applied to elucidate changes in surface properties that
      occur with aging. Specifically, studies of the surface properties of human
      retinal pigment epithelium melanosomes as a function of age are stimulating the
      development of models for their age-dependent behaviors. The article concludes
      with a brief discussion of important unanswered research questions in this field.

PMID- 18817438
TI  - Shape-controlled platinum nanocubes and their assembly into two-dimensional and
      three-dimensional superlattices.
AB  - Liquid-liquid phase transfer has been used to synthesize platinum nanocrystals
      with a cubic morphology. By finely tuning the parameters controlling the
      nucleation and growth processes, nanometric truncated cubes or perfect cubes may
      be obtained. To our knowledge, this is the first time such shapes are obtained
      with this procedure. The importance of both the length of the capping agent to
      control the growth process and the bromide anions as poison for the (111) facet
      is shown. The low degree of size polydispersity allows these nanocrystals to self
      assemble with a long-range ordering in two-dimensional and three-dimensional
      supracrystals. According to the nanocrystal shape, simple cubic or face-centered
      cubic supracrystals are observed. It is remarkable to notice that well-faceted
      supracrystals with sizes on the order of 10 microm may be obtained.

PMID- 18817439
TI  - Emulsion templated scaffolds that include gelatin and glycosaminoglycans.
AB  - Gelatin is one of the most commonly used biopolymer for creating cellular
      scaffolds due to its innocuous nature. To create stable gelatin scaffolds at
      physiological temperature (37 degrees C), chemical cross-linking is a necessary
      step. In a previous paper (Biomacromolecules 2006, 7, 3059-3068), cross-linking
      was carried out by either radical polymerization of the methacrylated derivative
      of gelatin (GMA) or through the formation of isopeptide bonds catalyzed by
      transglutaminase. The method of scaffold production was based on emulsion
      templating in which an organic phase is dispersed in the form of discrete
      droplets into a continuous aqueous solution of the biopolymer. Both kinds of
      scaffolds were tested as culture medium for hepatocytes. It turned out that the
      enzymatic cross-linked scaffold performed superiorily in this respect, even
      though it was mechanically less stable than the GMA scaffold. In the present
      paper, in an attempt to improve the biocompatibility of the GMA-based scaffold,
      biopolymers present in the extracellular matrix (ECM) were included in scaffold
      formulation, namely, chondroitin sulfate and hyaluronic acid. These biopolymers
      were derivatized with methacrylic moieties to undergo radical polymerization
      together with GMA. The morphology of the scaffolds was tuned to some extent by
      varying the volume fraction of the internal phase and to a larger extent by
      inducing a controlled destabilization of the precursor emulsion through the use
      of additives. In this way, scaffolds with 44% of the void volume attributable to
      voids with a diameter exceeding 60 microm and with 79% of the interconnect area
      attributable to interconnects with a diameter exceeding 20 microm in diameter
      could be successfully synthesized. To test whether the inclusion of ECM
      components into scaffold formulation resolves in an improvement of their
      biocompatibility with respect to GMA scaffolds, hepatocytes were seeded on both
      kinds of scaffolds and cell viability and function assays were carried out and
      compared.

PMID- 18817440
TI  - Photo-cross-linked PLA-PEO-PLA hydrogels from self-assembled physical networks:
      mechanical properties and influence of assumed constitutive relationships.
AB  - Poly(lactide)-block-poly(ethylene oxide)-block-poly(lactide) (PLA-PEO-PLA)
      triblock copolymers are known to form physical hydrogels in water as a result of
      the polymer's amphiphilicity. Their mechanical properties, biocompatibility, and
      biodegradability have made them attractive for use as soft tissue scaffolds.
      However, the network junction points are not covalently cross-linked, and in a
      highly aqueous environment these hydrogels adsorb more water, transform from gel
      to sol, and lose the designed mechanical properties. In this article, a hydrogel
      was formed by the use of a novel two-step approach. In the first step, the end
      functionalized PLA-PEO-PLA triblock was self-assembled into a physical hydrogel
      through hydrophobic micelle network junctions, and in the second step, this self
      assembled physical network structure was locked into place by photo-cross-linking
      the terminal acrylate groups. In contrast with physical hydrogels, the photo
      cross-linked gels remained intact in phosphate-buffered solution at body
      temperature. The swelling, degradation, and mechanical properties were
      characterized, and they demonstrated an extended degradation time (approximately
      65 days), an exponential decrease in modulus with degradation time, and a tunable
      shear modulus (1.6-133 kPa). We also discuss the various constitutive
      relationships (Hookean, neo-Hookean, and Mooney-Rivlin) that can be used to
      describe the stress-strain behavior of these hydrogels. The chosen model and
      assumptions used for data fitting influenced the obtained modulus values by as
      much as a factor of 3.5, which demonstrates the importance of clearly stating
      one's data fitting parameters so that accurate comparisons can be made within the
      literature.

PMID- 18817441
TI  - Synthesis and characterization of biodegradable peptide-based polymers prepared
      by microwave-assisted click chemistry.
AB  - In this study, the microwave-assisted copper(I)-catalyzed 1,3-dipolar
      cycloaddition reaction was used to synthesize peptide triazole-based polymers
      from two novel peptide-based monomers: azido-phenylalanyl-alanyl-lysyl-propargyl
      amide (1) and azido-phenylalanyl-alanyl-glycolyl-lysyl-propargyl amide (2). The
      selected monomers have sites for enzymatic degradation as well as for chemical
      hydrolysis to render the resulting polymer biodegradable. Depending on the
      monomer concentration in DMF, the molecular mass of the polymers could be
      tailored between 4.5 and 13.9 kDa (corresponding with 33-100 amino acid residues
      per polymer chain). As anticipated, both polymers can be enzymatically degraded
      by trypsin and chymotrypsin, whereas the ester bond in the polymer of 2 undergoes
      chemical hydrolysis under physiological conditions, as was shown by a ninhydrin
      based colorimetric assay and MALDI-TOF analysis. In conclusion, the microwave
      assisted copper(I)-catalyzed 1,3-dipolar cycloaddition reaction is an effective
      tool for synthesizing biodegradable peptide polymers, and it opens up new
      approaches toward the synthesis of (novel) designed biomedical materials.

PMID- 18817444
TI  - Meroditerpenoids from the brown alga Sargassum siliquastrum.
AB  - Eleven new meroditerpenoids (7-11, 14-17, 19, 20) and nine known compounds (1-6,
      12, 13, 18) were isolated from the brown alga Sargassum siliquastrum. Combined
      chemical and spectroscopic analyses revealed a common tetraprenyl hydroquinone
      structure; these compounds belonged to the nahocol, isonahocol, and
      sargahydroquinoic acid classes. The dihydroquinone moiety of 20 was unique and
      unprecedented in a brown alga. Stereochemical assignments were made for several
      of the known compounds based on their chemical reactivity. These compounds
      exhibited moderate to significant radical-scavenging activity as well as weak
      inhibitory activities against sortase A and isocitrate lyase.

PMID- 18817445
TI  - Phthalides from Pittosporum illicioides var. illicioides with inhibitory activity
      on superoxide generation and elastase release by neutrophils.
AB  - Six new phthalides, (S)-3-ethyl-7-hydroxy-6-methoxyphthalide (1), (S)-3-ethyl-7
      hydroxy-5,6-dimethoxyphthalide (2), (S)-3-ethyl-5,6,7-trimethoxyphthalide (3),
      (R)-3-ethyl-7-hydroxy-6-methoxyphthalide (4), (Z)-3-ethylidene-7-hydroxy-6
      methoxyphthalide (5), and (Z)-3-ethylidene-6,7-dimethoxyphthalide (6), have been
      isolated from the root of Pittosporum illicioides var. illicioides, together with
      seven known compounds. The structures of these new compounds were determined
      through spectroscopic and MS analyses. Compounds 1-4 exhibited inhibition
      (IC50<or=29.8 microM) of superoxide anion generation by human neutrophils in
      response to formyl-L-methionyl-L-leucyl-L-phenylalanine/cytochalasin B (fMLP/CB).
      Compounds 5 and 6 inhibited fMLP/CB-induced elastase release with IC50 values of
      38.6+/-4.3 and 33.9+/-3.9 microM, respectively.

PMID- 18817447
TI  - A pyrenyl-appended triazole-based calix[4]arene as a fluorescent sensor for Cd2+
      and Zn2+.
AB  - The synthesis and evaluation of a novel calix[4]arene-based fluorescent
      chemosensor 8 for the detection of Cd(2+) and Zn(2+) is described. The
      fluorescent spectra changes observed upon addition of various metal ions show
      that 8 is highly selective for Cd(2+) and Zn(2+) over other metal ions. Addition
      of Cd(2+) and Zn(2+) to the solution of 8 results in ratiometric measurement.

PMID- 18817448
TI  - Vilsmeier-Haack reaction of 1-cyclopropyl-2-arylethanones.
AB  - A convenient and efficient method to synthesize 3-(2-chloroethyl)-5-aryl-4H-pyran
      4-ones 2 and 2-chloro-3-(2-chloroethyl)-1-naphthaldehydes 3 in moderate to good
      yields was developed via the Vilsmeier-Haack reaction of readily available 1
      cyclopropyl-2-arylethanones 1 at different temperature. This reaction proceeds
      via sequential enolization, ring opening, haloformylation, and intramolecular
      nucleophilic cyclization or Friedel-Crafts alkylation reactions to produce 2 or
      3.

PMID- 18817449
TI  - Ru3(CO)12-catalyzed reactions of catechols with alkynes: an atom-economic process
      for the synthesis of 2,2-disubstituted 1,3-benzodioxoles from the double addition
      of the O-H bond across a triple bond.
AB  - Ru3(CO)12 has been found to be the efficient catalyst for the addition reactions
      of catechols with both terminal and internal alkynes to selectively afford 2,2
      disubstituted 1,3-benzodioxoles in good to high yields. The formation of 2,2
      substituted 1,3-benzodioxoles results from the tandem addition of two O-H bonds
      of catechols to alkyne's triple bond.

PMID- 18817450
TI  - Syntheses of 1,3-imidazolin-2-ones and 1,3-imidazolin-2-thiones from new building
      blocks, gamma-aminoacetoacetanilides.

PMID- 18817451
TI  - Metallic nanowires by full wafer stencil lithography.
AB  - Aluminum and gold nanowires were fabricated using 100 mm stencil wafers
      containing nanoslits fabricated with a focused ion beam. The stencils were
      aligned and the nanowires deposited on a substrate with predefined electrical
      pads. The morphology and resistivity of the wires were studied. Nanowires down to
      70 nm wide and 5 mum long have been achieved showing a resistivity of 10
      microOmegacm for Al and 5 microOmegacm for Au and maximum current density of
      approximately 10(8) A/cm(2). This proves the capability of stencil lithography
      for the fabrication of metallic nanowires on a full wafer scale.

PMID- 18817452
TI  - Factors governing helix formation in peptides confined to carbon nanotubes.
AB  - The effect of confinement on the stability and dynamics of peptides and proteins
      is relevant in the context of a number of problems in biology and biotechnology.
      We have examined the stability of different helix-forming sequences upon
      confinement to a carbon nanotube using Langevin dynamics simulations of a coarse
      grained representation of the polypeptide chain. We show that the interplay of
      several factors that include sequence, solvent conditions, strength (lambda) of
      nanotube-peptide interactions, and the nanotube diameter (D) determines
      confinement-induced stability of helicies. In agreement with predictions based on
      polymer theory, the helical state is entropically stabilized for all sequences
      when the interaction between the peptide and the nanotube is weakly hydrophobic
      and D is small. However, there is a strong sequence dependence as the strength of
      the lambda increases. For an amphiphilic sequence, the helical stability
      increases with lambda, whereas for polyalanine the diagram of states is a complex
      function of lambda and D. In addition, decreasing the size of the "hydrophobic
      patch" lining the nanotube, which mimics the chemical heterogeneity of the
      ribosome tunnel, increases the helical stability of the polyalanine sequence. Our
      results provide a framework for interpreting a number of experiments involving
      the structure formation of peptides in the ribosome tunnel as well as transport
      of biopolymers through nanotubes.

PMID- 18817454
TI  - Two new species of Gyrodactylus von Nordmann, 1832 (Monogenea: Gyrodactylidae)
      parasitizing Girardinichthys multiradiatus (Cyprinodontiformes: Goodeidae), an
      endemic freshwater fish from central Mexico.
AB  - Gyrodactylus mexicanus n. sp. and Gyrodactylus lamothei n. sp. are described from
      the fins and skin of Girardinichthys multiradiatus, an endemic freshwater fish
      from central Mexico. Gyrodactylus mexicanus is compared to other Gyrodactylus
      species that parasitize Fundulus spp., the phylogenetically closest group to the
      Goodeidae from North America. Gyrodactylus mexicanus is distinguished by having
      large anchors with well-developed superficial roots, enlarged hooks with a
      proximally disrupted shank (ligament), and a ventral bar with 2 poorly developed
      anterolateral projections and a small medial process. Gyrodactylus lamothei is
      distinguished from G. mexicanus and from other species of Gyrodactylus on the
      North American continent by having anchors with a sclerite on the superficial
      root and robust hooks with a straight shaft and a recurved point.

PMID- 18817453
TI  - Rice XB15, a protein phosphatase 2C, negatively regulates cell death and XA21
      mediated innate immunity.
AB  - Perception of extracellular signals by cell surface receptors is of central
      importance to eukaryotic development and immunity. Kinases that are associated
      with the receptors or are part of the receptors themselves modulate signaling
      through phosphorylation events. The rice (Oryza sativa L.) XA21 receptor kinase
      is a key recognition and signaling determinant in the innate immune response. A
      yeast two-hybrid screen using the intracellular portion of XA21, including the
      juxtamembrane (JM) and kinase domain as bait, identified a protein phosphatase 2C
      (PP2C), called XA21 binding protein 15 (XB15). The interaction of XA21 and XB15
      was confirmed in vitro and in vivo by glutathione-S-transferase (GST) pull-down
      and co-immunoprecipitation assays, respectively. XB15 fusion proteins purified
      from Escherichia coli and from transgenic rice carry PP2C activity.
      Autophosphorylated XA21 can be dephosphorylated by XB15 in a temporal- and dosage
      dependent manner. A serine residue in the XA21 JM domain is required for XB15
      binding. Xb15 mutants display a severe cell death phenotype, induction of
      pathogenesis-related genes, and enhanced XA21-mediated resistance. Overexpression
      of Xb15 in an XA21 rice line compromises resistance to the bacterial pathogen
      Xanthomonas oryzae pv. oryzae. These results demonstrate that Xb15 encodes a PP2C
      that negatively regulates the XA21-mediated innate immune response.

PMID- 18817455
TI  - Ultrastructural study of spermiogenesis and the spermatozoon of Microcotyle
      pancerii (Monogenea: Polyopisthocotylea: Microcotylidae), parasite of meagre
      Argyrosomus regius (Pisces: Teleostei).
AB  - The present work deals with the ultrastructure of spermiogenesis and the
      spermatozoon of Microcotyle pancerii, a gill parasite of meagre Argyrosomus
      regius collected in Corsican fish farms. Spermiogenesis was rather similar to
      that observed in other polyopisthocotylean Monogenea. The intercentriolar body
      was different from that described in digeneans. The nuclear condensation occurred
      in 2 successive stages. First, during the nuclear migration in the median
      cytoplasmic process, the nucleus developed a honeycomb-like appearance. Then,
      after the flagellar fusion, a discontinuous twisting of the chromatin appeared
      along the nucleus, with this process ending in total nuclear condensation. The
      structure of the spermatozoon is characterized by 2 axonemes (9 + "1" pattern), a
      single and continuous field of cortical microtubules, a mitochondrion, and a
      nucleus. Our findings were compared with various ultrastructural features in
      order to highlight variability within the group.

PMID- 18817456
TI  - Cross-species utility of microsatellite markers in trichostrongyloid nematodes.
AB  - The development of microsatellite markers for parasitic nematodes has been
      hampered by technical difficulties in isolation and PCR amplification. We have
      investigated the potential for circumventing these problems using microsatellites
      from 3 trichostrongyloid species on a panel of 7 species. Ten of the 22 PCR
      primer pairs tested amplified in species other than the target species, usually
      in closely related species, and 2 new variable loci were discovered in the sheep
      parasite Trichostrongylus vitrinus. This study provides evidence that cross
      species testing of microsatellite primers can be an effective alternative to
      isolation de novo.

PMID- 18817457
TI  - A national risk assessment for intersex in fish arising from steroid estrogens.
AB  - The occurrence of intersex fish is widespread in the rivers of England and Wales.
      The extent of intersex in fish populations is believed to be strongly linked to
      their exposure to steroid estrogens. The present study presents, to our
      knowledge, the first national, catchment-based risk assessment for steroid
      estrogens in the world. A graphical information system-based model predicted the
      concentrations of estradiol (E2), estrone, and ethinylestradiol, which were
      combined and compared with known biological effect levels to predict the risk of
      endocrine disruption for 10,313 individual river reaches (21,452 km) receiving
      effluent from more than 2000 sewage treatment plants serving more than 29 million
      people. The large scale of this assessment underlines the usefulness of computer
      based risk assessment methods. Overall, 61% [corrected] of the modeled reaches
      (all percentages are in terms of the total river length modeled) in England and
      Wales were predicted to be not at risk from endocrine disruption (mean
      concentrations, <1 ng/L E2 equivalents). A large range existed in the percentage
      of river reaches at risk in the various regions, from 5% in Wales to 67% in the
      Thames catchment. Important factors influencing this proportion are the
      population density, particularly their location, and the available dilution. A
      very small proportion of reaches (approximately 1-3%) were predicted to be at
      high risk (>10 ng/L E2 equivalents). Many of these high-risk reaches, however,
      were ditches, which were composed almost entirely of sewage effluent. The model
      could be applied equally well to any other chemical of concern emanating from the
      human population that would be impractical to assess by measurement.

PMID- 18817458
TI  - Environmental variation, stochastic extinction, and competitive coexistence.
AB  - Understanding how environmental fluctuations affect population persistence is
      essential for predicting the ecological impacts of expected future increases in
      climate variability. However, two bodies of theory make opposite predictions
      about the effect of environmental variation on persistence. Single-species
      theory, common in conservation biology and population viability analyses,
      suggests that environmental variation increases the risk of stochastic
      extinction. By contrast, coexistence theory has shown that environmental
      variation can buffer inferior competitors against competitive exclusion through a
      storage effect. We reconcile these two perspectives by showing that in the
      presence of demographic stochasticity, environmental variation can increase the
      chance of extinction while simultaneously stabilizing coexistence. Our stochastic
      simulations of a two-species storage effect model reveal a unimodal relationship
      between environmental variation and coexistence time, implying maximum
      coexistence at intermediate levels of environmental variation. The unimodal
      pattern reflects the fact that the stabilizing influence of the storage effect
      accumulates rapidly at low levels of environmental variation, whereas the risk of
      extinction due to the combined effects of environmental variation and demographic
      stochasticity increases most rapidly at higher levels of variation. Future
      increases in environmental variation could either increase or decrease an
      inferior competitor's expected persistence time, depending on the distance
      between the present level of environmental variation and the optimal level
      anticipated by this theory.

PMID- 18817459
TI  - Life-history variation in contrasting habitats: flowering decisions in a clonal
      perennial herb (Veratrum album).
AB  - Quantifying intraspecific demographic variation provides a powerful tool for
      exploring the diversity and evolution of life histories. We investigate how
      habitat-specific demographic variation and the production of multiple offspring
      types affect the population dynamics and evolution of delayed reproduction in a
      clonal perennial herb with monocarpic ramets (white hellebore). In this species,
      flowering ramets produce both seeds and asexual offspring. Data on ramet
      demography are used to parameterize integral projection models, which allow the
      effects of habitat-specific demographic variation and reproductive mode on
      population dynamics to be quantified. We then use the evolutionarily stable
      strategy (ESS) approach to predict the flowering strategy-the relationship
      between flowering probability and size. This approach is extended to allow
      offspring types to have different demographies and density-dependent responses.
      Our results demonstrate that the evolutionarily stable flowering strategies
      differ substantially among habitats and are in excellent agreement with the
      observed strategies. Reproductive mode, however, has little effect on the ESSs.
      Using analytical approximations, we show that flowering decisions are
      predominantly determined by the asymptotic size of individuals rather than
      variation in survival or size-fecundity relationships. We conclude that habitat
      is an important aspect of the selective environment and a significant factor in
      predicting the ESSs.

PMID- 18817460
TI  - Prospects for life span extension.
AB  - Life expectancy has increased dramatically in the United States and in much of
      the world in recent years and decades. The factors underlying this increase are
      incompletely understood and are undoubtedly complex. A question that drives
      current research is whether life expectancy can be further extended using current
      knowledge of modifiable risk factors. A still more challenging research focus is
      on the possibility that life expectancy might be further increased through
      knowledge gained from studies of the basic biology of aging and its genetic and
      environmental modifiers.

PMID- 18817461
TI  - Necrotizing enterocolitis.
AB  - Necrotizing enterocolitis (NEC) remains a major cause of neonatal morbidity and
      death. The pathophysiology is poorly understood. Prevailing evidence suggests
      that NEC is due to an inappropriate inflammatory response of the immature gut to
      some undefined insult. The mortality rate (15%-25%) for affected infants has not
      changed appreciably in 30 years. Many infants with NEC recover uneventfully with
      medical therapy and have long-term outcomes similar to unaffected infants of
      matched gestational age. Infants with progressive disease requiring surgical
      intervention suffer almost all of the mortality and morbidity. Of these,
      approximately 30%-40% will die of their disease and most of the remainder will
      develop long-term neurodevelopmental and gastrointestinal morbidity. Recent
      randomized trials suggest that the choice of operation does not influence patient
      outcome. Current work is focusing on developing a better understanding of the
      pathogenesis and improving means to identify which infants are at greatest risk
      of disease progression.

PMID- 18817462
TI  - Function follows form: shape complementarity and nanoparticle toxicity.

PMID- 18817463
TI  - Environmental challenges for nanomedicine.

PMID- 18817466
TI  - Enhanced imaging and accelerated photothermalysis of A549 human lung cancer cells
      by gold nanospheres.
AB  - BACKGROUND & AIMS: Gold nanoparticles are excellent photon-thermal energy
      converters. The purpose of this work was to investigate the influence of gold
      nanoparticles on the photothermalysis of A549 lung tumor cells. MATERIALS &
      METHODS: A549 lung tumor cells were exposed to goat antihuman immunoglobulin
      (Ig)G-conjugated gold nanospheres (40 nm) and were then imaged under a dark-field
      microscope. The live cells were then subjected to photoirradiation using a 633-nm
      laser at different power levels. The viability of tumor cells under laser
      irradiation was monitored by confocal microscopy using a viability-assay kit.
      RESULTS & DISCUSSION: The death rates of A549 lung tumor cells after gold
      nanoparticle exposure increased significantly under laser irradiation. The
      maximum initial cell death rate was observed at a laser power level of 3.75 mW,
      with the initial deactivation rate accelerated by a factor of 6.6 and a total
      loss of 92% of cell viability. CONCLUSION: This work demonstrated potential
      applications of gold nanospheres as both imaging probes and enhancing agents for
      photothermal therapy of cancer.

PMID- 18817467
TI  - Reactive oxygen species scavenging properties of ZrO2-CeO2 solid solution
      nanoparticles.
AB  - AIMS: The hypothesis that an increase in defects in cerium oxide (CeO(2))
      nanoparticles induced by solid solutions with differences in valency and ionic
      radius of the solute will yield superior reactive oxygen species (ROS) scavengers
      at room temperature will be tested. METHODS: Solid solutions of zirconium in
      CeO(2), that is, Ce(x)Zr(1-x)O(2) nanoparticles, were synthesized by a reverse
      micelle method. Their crystal structures, particle sizes and level of
      agglomeration were characterized. The nanoparticles' activities to scavenge ROS
      were tested in response to hydrogen peroxide at physiological levels and room
      temperature using an enzyme peroxidase-based assay. RESULTS: Solid solutions of
      Zr in CeO(2) nanoparticles enhanced ROS scavenging fourfold. The hypothesis is
      confirmed that more defects are formed and that the scavenging activities of
      Ce(x)Zr(1-x)O(2) correlate to the nanoparticles' oxygen-storage capacity.
      CONCLUSIONS: The antioxidant efficacy of CeO(2) nanoparticles can be enhanced by
      dissolving zirconium in the CeO(2) lattice. The Ce(x)Zr(1-x)O(2) nanoparticles
      act as an enhanced catalyst at room temperature that scavenges ROS. Increased
      efficacy will enable lower nanoparticle dosages to protect cells from ROS, thus
      increasing the therapeutic width of these compounds.

PMID- 18817468
TI  - LANTCET: elimination of solid tumor cells with photothermal bubbles generated
      around clusters of gold nanoparticles.
AB  - BACKGROUND: We have developed a method, termed laser-activated nano-thermolysis
      as a cell elimination technology (LANTCET), for the selective detection and
      destruction of individual tumor cells by the generation of intracellular
      photothermal bubbles around clusters of gold nanoparticles. METHOD: Bare
      nanoparticles and their conjugates to C225 tumor-specific monoclonal antibodies
      were applied in vitro to C225-positive squamous carcinoma cells and in vivo to an
      experimental tumor in a rat in order to form intracellular clusters of
      nanoparticles. RESULTS: Single 10 ns laser pulses generated intracellular
      photothermal microbubbles at a near-infrared and visible wavelengths. The cells
      with the clusters yielded an almost 100-fold decrease in the laser fluence
      threshold for bubble generation and cell damage relative to that for the cells
      without clusters. Cell damage had a mechanical origin and single cell
      selectivity. Three LANTCET processes (cell detection, damage and optical
      guidance) were realized as a microsecond sequence and with the one device.

PMID- 18817469
TI  - Novel bio-nanochip based on localized surface plasmon resonance spectroscopy of
      rhombic nanoparticles.
AB  - A new silver (Ag) nanostructure with a rectangular distribution array composed of
      rhombic nanoparticles is described here. The structure has an apparent advantage
      of strong hot spots that have a much higher signal intensity than that of the
      previously reported traditional triangular structures. It generates a great
      enhancement of a localized surface plasmon resonance (LSPR) effect. Moreover, an
      antigen with longer arm length is applied to strengthen the binding signals of
      both the antigen and antibody. We performed experiments for the LSPR-induced
      extinction spectra in each step of the surface modification of the Ag
      nanoparticles in atmosphere environment. A spectrophotometer was used to measure
      the extinction spectrum of our proposed nanochip. The results obtained indicate a
      better sensitivity for our current nanochip than that of the other reported LSPR
      based nanochips. Theoretical computational numerical simulation is also carried
      out with a discrete dipole approximation algorithm. Our computational results are
      in agreement with the corresponding experimental spectrum. This type of nanochip
      may have potential utility in many applications, including medical science,
      biological fields and biochemical analysis.

PMID- 18817470
TI  - Dendrimers for enhanced drug solubilization.
AB  - Approximately 40% of newly developed drugs are rejected by the pharmaceutical
      industry and will never benefit a patient because of low water solubility.
      Another 17% of launched drugs exhibit suboptimal performance for the same reason.
      Given the growing impact and need for drug delivery, a thorough understanding of
      delivery technologies that enhance the bioavailability of drugs is important. The
      high level of control over the dendritic architecture (size, branching density,
      surface functionality) makes dendrimers ideal excipients for enhanced solubility
      of poorly water-soluble drugs. Many commercial small-molecule drugs with
      anticancer, anti-inflammatory and antimicrobial activity have been formulated
      successfully with dendrimers, such as poly(amidoamine) (PAMAM), poly(propylene
      imine) (PPI or DAB) and poly(etherhydroxylamine) (PEHAM). Some dendrimers
      themselves show pharmaceutical activity in these three areas, providing the
      opportunity for combination therapy in which the dendrimers serve as the drug
      carrier and simultaneously as an active part of the therapy.

PMID- 18817471
TI  - Clearance properties of nano-sized particles and molecules as imaging agents:
      considerations and caveats.
AB  - Nanoparticles possess enormous potential as diagnostic imaging agents and hold
      promise for the development of multimodality agents with both imaging and
      therapeutic capabilities. Yet, some of the most promising nanoparticles
      demonstrate prolonged tissue retention and contain heavy metals. This presents
      serious concerns for toxicity. The creation of nanoparticles with optimal
      clearance characteristics will minimize toxicity risks by reducing the duration
      of exposure to these agents. Given that many nanoparticles possess easily
      modifiable surface and interior chemistry, if nanoparticle characteristics
      associated with optimal clearance from the body were well established, it would
      be feasible to design and create agents with more favorable clearance properties.
      This article presents a thorough discussion of the physiologic aspects of
      nanoparticle clearance, focusing on renal mechanisms, and provides an overview of
      current research investigating clearance of specific types of nanoparticles and
      nano-sized macromolecules, including dendrimers, quantum dots, liposomes and
      carbon, gold and silica-based nanoparticles.

PMID- 18817472
TI  - Computer-aided applications of nanoscale smart materials for biomedical
      applications.
AB  - Nanotechnology has the potential to impact the treatment of many diseases that
      currently plague society: cancer, AIDS, dementia of various kinds and so on.
      Nanoscale smart materials, such as carbon nanotubes, C(60), dendrimers and
      cyclodextrins, hold great promise for use in the development of better
      diagnostics, drug delivery and the alteration of biological function. Although
      experimentation is being used to explore the potential offered by these
      materials, it is by its very nature expensive in terms of time, resources and
      expertise. Insight with respect to the behavior of these materials in the
      presence of biological entities can be obtained much more rapidly by molecular
      dynamics simulation. Furthermore, the results of simulation may be used to guide
      experimentation so that it is much more productive than it might be in the
      absence of such information. The interactions of several nanoscale structures
      with biological macromolecules can already be probed effectively using molecular
      dynamics simulation. The results obtained should form the basis for significant
      new developments in the treatment of disease.

PMID- 18817474
TI  - Effect of 655-nm low-level laser therapy on exercise-induced skeletal muscle
      fatigue in humans.
AB  - OBJECTIVE: To investigate if development of skeletal muscle fatigue during
      repeated voluntary biceps contractions could be attenuated by low-level laser
      therapy (LLLT). BACKGROUND DATA: Previous animal studies have indicated that LLLT
      can reduce oxidative stress and delay the onset of skeletal muscle fatigue.
      MATERIALS AND METHODS: Twelve male professional volleyball players were entered
      into a randomized double-blind placebo-controlled trial, for two sessions (on day
      1 and day 8) at a 1-wk interval, with both groups performing as many voluntary
      biceps contractions as possible, with a load of 75% of the maximal voluntary
      contraction force (MVC). At the second session on day 8, the groups were either
      given LLLT (655 nm) of 5 J at an energy density of 500 J/cm2 administered at each
      of four points along the middle of the biceps muscle belly, or placebo LLLT in
      the same manner immediately before the exercise session. The number of muscle
      contractions with 75% of MVC was counted by a blinded observer and blood lactate
      concentration was measured. RESULTS: Compared to the first session (on day 1),
      the mean number of repetitions increased significantly by 8.5 repetitions (+/-
      1.9) in the active LLLT group at the second session (on day 8), while in the
      placebo LLLT group the increase was only 2.7 repetitions (+/- 2.9) (p = 0.0001).
      At the second session, blood lactate levels increased from a pre-exercise mean of
      2.4 mmol/L (+/- 0.5 mmol/L), to 3.6 mmol/L (+/- 0.5 mmol/L) in the placebo group,
      and to 3.8 mmol/L (+/- 0.4 mmol/L) in the active LLLT group after exercise, but
      this difference between groups was not statistically significant. CONCLUSION: We
      conclude that LLLT appears to delay the onset of muscle fatigue and exhaustion by
      a local mechanism in spite of increased blood lactate levels.

PMID- 18817475
TI  - Functional gait evaluation of collagen chitosan nerve guides for sciatic nerve
      repair.
AB  - The objective of this work was to use a functional gait analysis technique to
      evaluate sciatic nerve repair through tissue-engineered nerve guides in a rodent
      animal model. The nerve guides were fabricated by blending collagen with chitosan
      material and evaluated over a 12-week period for motor and sensory nerve recovery
      assessed by gait analysis and behavioral testing. Gastrocnemius muscle weight
      measurements were obtained at the end of each experimental time point and
      correlated to motor nerve recovery. Functional gait analysis studied both the
      stance and swing phase angle formations during a normal gait cycle. During the
      stance phase, functional results revealed that blended nerve guides promoted
      increased motor nerve recovery than unblended chitosan nerve guides. Similar
      results were obtained from behavioral tests, indicating that blended nerve guides
      created increased sensitivity to applied stimulus compared to unblended nerve
      guides. Muscle strength also correlated with functional recovery and was
      significantly higher when compared to the unblended nerve guides. From this
      study, we conclude that collagen-blended chitosan nerve guides enhanced motor and
      sensory nerve recovery assayed through gait and behavioral testing compared to
      unblended nerve guides.

PMID- 18817476
TI  - X-ray microtomographic imaging of three-dimensional structure of soft tissues.
AB  - We report the x-ray microtomographic imaging of three-dimensional (3D) structure
      of soft tissues. The transparency of biological tissue to hard x-rays enables
      radiographic analysis of tissue entrails. However, biological tissues are mainly
      composed of light elements, which produce little contrast in a hard x-ray
      transmission image. Tissue structures were visualized by contrasting biological
      constituents with heavy elements. Efficient x-ray absorption by heavy-element
      dyes allowed the radiographic visualization of microstructures of soft tissues.
      The high-resolution computed tomography analysis provided the 3D microstructure
      of these microcontrasted tissues. Element-selective visualization of the stained
      tissue using x-ray absorption edges revealed the specific architecture of
      internal components. The structures obtained were used for rapid prototyping,
      giving 3D copies of human capillary vessels and fruit fly body.

PMID- 18817477
TI  - The muscle stem cell niche: regulation of satellite cells during regeneration.
AB  - Satellite cells are considered to be adult skeletal muscle stem cells. Their
      ability to regenerate large muscle defects is highly dependent on their specific
      niche. When these cells are cultured in vitro, the loss of this niche leads to a
      loss of proliferative capacity and defective regeneration when implanted back
      into a muscle defect. The most important aspects of the niche will be discussed-
      in particular, the basement membrane, the niche's mechanical properties, its
      supporting cells, and the influence these features have on satellite cell
      activation, proliferation, and differentiation. Understanding more about the
      control of these satellite cell activities by the niche will facilitate their
      recruitment and effective deployment for regenerative medicine.

PMID- 18817479
TI  - Latent variable modeling of differences and changes with longitudinal data.
AB  - This review considers a common question in data analysis: What is the most useful
      way to analyze longitudinal repeated measures data? We discuss some contemporary
      forms of structural equation models (SEMs) based on the inclusion of latent
      variables. The specific goals of this review are to clarify basic SEM
      definitions, consider relations to classical models, focus on testable features
      of the new models, and provide recent references to more complete presentations.
      A broader goal is to illustrate why so many researchers are enthusiastic about
      the SEM approach to data analysis. We first outline some classic problems in
      longitudinal data analysis, consider definitions of differences and changes, and
      raise issues about measurement errors. We then present several classic SEMs based
      on the inclusion of invariant common factors and explain why these are so
      important. This leads to newer SEMs based on latent change scores, and we explain
      why these are useful.

PMID- 18817478
TI  - Oral administration of blueberry inhibits angiogenic tumor growth and enhances
      survival of mice with endothelial cell neoplasm.
AB  - Endothelial cell neoplasms are the most common soft tissue tumor in infants.
      Subcutaneous injection of spontaneously transformed murine endothelial (EOMA)
      cells results in development of hemangioendothelioma (HE). We have previously
      shown that blueberry extract (BBE) treatment of EOMA cells in vitro prior to
      injection in vivo can significantly inhibit the incidence and size of developing
      HE. In this study, we sought to determine whether oral BBE could be effective in
      managing HE and to investigate the mechanisms through which BBE exerts its
      effects on endothelial cells. A dose-dependent decrease in HE tumor size was
      observed in mice receiving daily oral gavage feeds of BBE. Kaplan-Meier survival
      curve showed significantly enhanced survival for mice with HE tumors given BBE,
      compared to control. BBE treatment of EOMA cells inhibited both c-Jun N-terminal
      kinase (JNK) and NF-kappaB signaling pathways that culminate in monocyte
      chemoattractant protein-1 (MCP-1) expression required for HE development.
      Antiangiogenic effects of BBE on EOMA cells included decreased proliferation by
      BrdU assay, decreased sprouting on Matrigel, and decreased transwell migration.
      Thus, this work provides first evidence demonstrating that BBE can limit tumor
      formation through antiangiogenic effects and inhibition of JNK and NF-kappaB
      signaling pathways. Oral administration of BBE represents a potential therapeutic
      antiangiogenic strategy for treating endothelial cell neoplasms in children.

PMID- 18817480
TI  - Culture matters: a study on presence in an interactive movie.
AB  - A cross cultural study was conducted to test the influences of different cultural
      backgrounds on the user's presence experience in interacting with a distributed
      interactive movie. The effects of embodied interaction on presence were also
      investigated because embodiment is often used to enrich the experience and to
      reduce the complexity of distributed interaction. In absence of a clear
      definition of what cultural factors might influence presence, Dutch and Chinese
      participants were invited to the study to optimize cultural diversion. The
      results suggested that Chinese participants perceived more presence than Dutch
      participants in all conditions. The results also show that interaction methods
      (direct touch against remote control) had no influence, while embodiment (robot
      against screen agent) had mixed effects on presence.

PMID- 18817481
TI  - Computer games: a double-edged sword?
AB  - Excessive computer game playing (ECGP) has already become a serious social
      problem. However, limited data from experimental lab studies are available about
      the negative consequences of ECGP on players' cognitive characteristics. In the
      present study, we compared three groups of participants (current ECGP
      participants, previous ECGP participants, and control participants) on a Multiple
      Object Tracking (MOT) task. The previous ECGP participants performed
      significantly better than the control participants, which suggested a
      facilitation effect of computer games on visuospatial abilities. Moreover, the
      current ECGP participants performed significantly worse than the previous ECGP
      participants. This more important finding indicates that ECGP may be related to
      cognitive deficits. Implications of this study are discussed.

PMID- 18817482
TI  - Image, word, action: interpersonal dynamics in a photo-sharing community.
AB  - In online photo-sharing communities, the individual's expression of self and the
      relationships that evolve among members is determined by the kinds of images that
      are shared, by the words exchanged among members, and by interpersonal actions
      that do not specifically rely on images or text. This article examines the
      dynamics of personal expression via images in Flickr, including a proposed system
      for identifying the dimensions of imagistic communication and a discussion of the
      psychological meanings embedded in a sequence of images. It explores how
      photographers use text descriptors to supplement their images and how different
      types of comments on photographs influence interpersonal relationships. The "fav"
      -when members choose an image as one of their favorites--is examined as one type
      of action that can serve a variety of interpersonal functions. Although images
      play a powerful role in the expression of self, it is the integration of images,
      words, and actions that maximize the development of relationships.

PMID- 18817483
TI  - The impact of emotional intelligence, self-esteem, and self-image on romantic
      communication over MySpace.
AB  - A study based on a survey of 240 individual MySpace users found that low self
      esteem encourages young adults to engage in romantic communication (such as
      having intimate communication with the opposite sex and looking for romantic
      partners) while higher emotional intelligence discourages such activity. The
      results also suggested that those who have higher self-image, such as thinking
      themselves attractive and happy with their appearance, tend to engage in romantic
      communication. Limitations of the study and suggestion for future study are
      discussed.

PMID- 18817484
TI  - Predictors of drop-out in an Internet study of men who have sex with men.
AB  - Researchers have suggested the rising use of Internet to look for sexual partners
      is an important contributor to the resurgence in the incidence of sexually
      transmitted diseases (STDs) and HIV among men who have sex with men (MSM). Web
      based samples of this population reflect good geographical diversity for
      research, but a high drop-out rate creates a significant potential for bias,
      misrepresentation of population, and misinterpretation of data. This study aims
      to describe the demographics of an Internet sample of MSM and the differences
      between the completers and drop-outs. We analyzed data obtained from a cross
      sectional study using an online self-administered questionnaire for males, 18
      years or older, who were current U.S. residents, and who had sex with men. Of 850
      eligible participants, 404 (47.5%) were labeled as drop-outs. The completers and
      drop-outs differed significantly in age, education, country of birth, health
      insurance, time spent on Internet, location of computer access, types of sites
      visited, profile information, last homosexual experience, methods used to
      determine safety of partners, and type of sexual activities on real meets. Almost
      half of the participants dropped out before completion. Although the two groups
      did not differ in many of the items, high drop-out rates are a threat to the
      validity of such data. Drop-out constitutes a significant bias in Internet
      sexuality research and must be considered while interpreting the results of such
      studies.

PMID- 18817485
TI  - Outcome of an online mutual support group for college students with psychological
      problems.
AB  - This study set up and evaluated an online mutual support group for college
      students with psychological problems. In a 2 x 2 pre-post design, participants (N
      = 238) were randomly assigned to either the Information Only condition, giving
      access to a Web site containing information about student problems, or to the
      Support Group condition, giving access to an identical Web site with the addition
      of an online mutual support group. Participants in both conditions improved on
      two of the three outcome measures, the CORE-OM and the Satisfaction with Life
      Scale, but there was no evidence of differential outcome between the two
      conditions.

PMID- 18817486
TI  - The nonverbal communication functions of emoticons in computer-mediated
      communication.
AB  - Most past studies assume that computer-mediated communication (CMC) lacks
      nonverbal communication cues. However, Internet users have devised and learned to
      use emoticons to assist their communications. This study examined emoticons as a
      communication tool that, although presented as verbal cues, perform nonverbal
      communication functions. We therefore termed emoticons quasi-nonverbal cues.

PMID- 18817487
TI  - Predicting self-protections of online privacy.
AB  - An empirical study was conducted to examine the social psychological processes
      that may influence an individual's adoption of online privacy protection
      strategies. Building from the theory of planned behavior, a theoretical model
      predicting self-protection of online privacy was tested in the present study.
      This model accounted for nearly a quarter of the variability in actual adoption
      during a ten-day period immediately after participants completed the initial
      questionnaire. Overall, the present research provided a strong support for the
      theoretical utility of psychological factors and processes in online privacy
      related research.

PMID- 18817489
TI  - These times are a-changing!

PMID- 18817490
TI  - Telethinking: with Right Honorable Lord Roger Swinfen and Lady Pat Swinfen.
      Interview by Vicki Glaser.

PMID- 18817491
TI  - Innovative programs in telemedicine: the Mayerson Center for Safe and Healthy
      Children, Cincinnati Children's Hospital Medical Center.

PMID- 18817492
TI  - Merger and acquisition trends in telemedicine.

PMID- 18817493
TI  - Diabetes management assisted by telemedicine: patient perspectives.
AB  - This qualitative research focuses on understanding the experiences of elderly
      patients with diabetes who participated in a telemedicine case management
      intervention, to better understand the barriers to success of telemedicine with
      the elderly. Telephone interviews were conducted with elderly patients with
      diabetes prior to and 6 and 12 months after participating in a case management
      intervention delivered via a computer that allowed them to teleconference with a
      nurse and dietitian, upload blood glucose and blood pressure data, and access
      educational materials. Qualitative analyses revealed that patients enrolled
      primarily because healthcare providers encouraged them. Their goals were to
      improve diabetes control, with few expectations of an effect on emotional health
      or family relationships. After involvement, they particularly valued the emphasis
      on monitoring of health outcomes and supportive contact with diabetes staff to
      encourage, remind, and answer questions. Findings illustrate the potential value
      of telemedicine with elderly patients with diabetes, if supported by primary care
      providers and including consistent, supportive interactions with knowledgeable
      diabetes healthcare providers.

PMID- 18817494
TI  - A remote fuzzy multicriteria diagnosis of sore throat.
AB  - A sore throat (also known as pharyngitis or tonsillitis) is most commonly caused
      by a contagious viral infection (such as the flu, cold, or mononucleosis),
      although more serious throat infections can be caused by a bacterial infection
      (such as strep, mycoplasma, or Haemophilus). Bacterial sore throats respond well
      to antibiotics, whereas viral ones do not. However, strep throat remains a
      leading cause for physician visits, and researchers have long struggled to
      determine how best to treat it. The current practice guidelines offer different
      management options for adult patients presenting with a sore throat. Thus, when a
      physician treats a patient with acute pharyngitis, the clinical decision that
      usually needs to be made is whether the pharyngitis is attributable to group A
      streptococci. The key concern is the degree to which the clinical possibility of
      a group A streptococcal infection should affect clinician's decisions. To
      determine the best treatment of pharyngitis, we conducted a multicriteria
      decision analysis using fuzzy reasoning for remote health service delivery
      between a healthcare provider and patients. The approach can be adopted for
      interactive phone use or online system application. Five alternative treatment
      options were considered, particularly: (a) no test no Rx, (b) rapid strep, (c)
      culture, (d) rapid strep and culture, and (e) empiric Rx. Fuzzy reasoning is used
      to examine the signs/symptoms and their ratings. The study includes seven
      criteria factors that can be rated according to each alternative clinical
      treatment using linguistic statements. The model shows that no test no Rx is the
      best option for the cases of low prevalence of group A streptococcal infection.
      Two strategies--culture and treat if positive and rapid strep with culture of
      negative results--are equally preferable for patients with moderate prevalence
      likelihood. Rapid strep and culture of negative results is the best management
      strategy for patients with high population prevalence of group A streptococcal
      infection. In conclusion, the best clinical management of patients with sore
      throat depends on both the clinical probability of group A streptococcal
      infection and clinical judgments that incorporate the importance ratings of the
      individual patients as well as practice circumstances.

PMID- 18817495
TI  - Digital image compression in dermatology: format comparison.
AB  - Digital image compression (reduction of the amount of numeric data needed to
      represent a picture) is widely used in electronic storage and transmission
      devices. Few studies have compared the suitability of the different compression
      algorithms for dermatologic images. We aimed at comparing the performance of four
      popular compression formats, Tagged Image File (TIF), Portable Network Graphics
      (PNG), Joint Photographic Expert Group (JPEG), and JPEG2000 on clinical and
      videomicroscopic dermatologic images. Nineteen (19) clinical and 15
      videomicroscopic digital images were compressed using JPEG and JPEG2000 at
      various compression factors and TIF and PNG. TIF and PNG are "lossless" formats
      (i.e., without alteration of the image), JPEG is "lossy" (the compressed image
      has a lower quality than the original), JPEG2000 has a lossless and a lossy mode.
      The quality of the compressed images was assessed subjectively (by three expert
      reviewers) and quantitatively (by measuring, point by point, the color
      differences from the original). Lossless JPEG2000 (49% compression) outperformed
      the other lossless algorithms, PNG and TIF (42% and 31% compression,
      respectively). Lossy JPEG2000 compression was slightly less efficient than JPEG,
      but preserved image quality much better, particularly at higher compression
      factors. For its good quality and compression ratio, JPEG2000 appears to be a
      good choice for clinical/videomicroscopic dermatologic image compression.
      Additionally, its diffusion and other features, such as the possibility of
      embedding metadata in the image file and to encode various parts of an image at
      different compression levels, make it perfectly suitable for the current needs of
      dermatology and teledermatology.

PMID- 18817496
TI  - Neurology diagnostics security and terminal adaptation for PocketNeuro project.
AB  - This paper presents new approaches of medical information security and terminal
      mobile phone adaptation for the PocketNeuro project. The latter term refers to a
      project created for the management of neurological diseases. It consists of
      transmitting information about patients ("desk of patients") to a doctor's mobile
      phone during a visit and examination of a patient. These new approaches for the
      PocketNeuro project were analyzed in terms of medical information security and
      adaptation of the diagnostic images to the doctor's mobile phone. Images were
      extracted from a DICOM library. Matlab and its library were used as software to
      test our approaches and to validate our results. Experiments performed on a
      database of 30 256 x 256 pixel-sized neuronal medical images indicated that our
      new approaches for PocketNeuro project are valid and support plans for large
      scale studies between French and Swiss hospitals using secured connections.

PMID- 18817497
TI  - Cost comparison between telemonitoring and usual care of heart failure: a
      systematic review.
AB  - Heart failure (HF) is associated with high direct and indirect costs to the
      patients and the healthcare system. This systematic review aims to analyze
      existing economic data to determine whether telemonitoring of patients with HF
      will result in decreased costs. The Scopus and PubMed databases were searched
      independently by two reviewers for journal articles that reported on an economic
      analysis (i.e., calculated monetary amounts or percentage change in costs) of a
      study using a HF telemonitoring system. Only articles describing telemonitoring
      systems with a component of home physiological measurements were included. Eleven
      articles met the inclusion criteria, describing 10 different HF telemonitoring
      systems. Nine of the 10 studies analyzed the direct costs to the healthcare
      system. All the studies found cost reductions from telemonitoring compared to
      usual care, which ranged between 1.6% and 68.3%. Cost reductions were mainly
      attributed to reduced hospitalization expenditures. Only one study discussed the
      impact of HF telemonitoring on direct patient costs. The study found a 3.5% lower
      travel cost for patients using telemonitoring compared to those in the usual care
      group. The single study that was found for indirect costs described the
      willingness to pay for telemedicine by patients with HF (55% of the patients with
      HF were willing to pay $20 to access telemedicine, and 19% were willing to pay
      $40). Available data from existing studies suggest that although HF
      telemonitoring will require an initial financial investment, it will
      substantially reduce costs in the long term, particularly by reducing
      rehospitalization and travel costs.

PMID- 18817498
TI  - E-collaboration for children with functional disabilities.
AB  - This paper describes the conceptual development and evaluation of an information
      technology (IT)-based cooperation system. The system, called CIDC, was developed
      at the University of Kalmar with the aim of facilitating communication,
      information, documentation, and collaboration concerning disabled children and
      their life situation. The study aims at finding out whether a system like this
      makes rehabilitation/habilitation work more effective. Previous experience shows
      that in conventional and non-IT-based communication, there are great deficiencies
      of cooperation between participants and the care, education, and welfare of a
      disabled child. We hypothesized that the system would improve the quality and
      overall implementation of efforts planned and carried out. The system has been
      tried in 8 families, all having a disabled child in the family. A group of 5-12
      users in each so-called e-room have cooperated concerning the child's life
      situation. The result shows that the parents are very satisfied that the system
      facilitates their work in many respects. The professional caregivers have also
      experienced obvious advantages, whereas a few, despite the quality-raising
      cooperation, are afraid it will involve more work. Many of the functions that the
      system has made available have been viewed positively, but the degree of
      utilization does not reach the same high level as its estimated usefulness. When
      the system is controlled by the parents, communication activities and usefulness
      estimations are higher than when the professionals are responsible. The system
      has proved easy to implement and has on the whole been felt to be user friendly.
      The experiment has been generally successful and will continue to be developed in
      cooperation with parent associations, enabling children with various disabilities
      to join.

PMID- 18817499
TI  - Clinical-technical performance and physician satisfaction with a transnational
      telephonic ECG system.
AB  - The effective use of cardiology hospital services could improve patient safety
      while shortening pre- and in-hospital stay periods using modern transtelephonic
      technologies and consultations by phone to follow up electrocardiograph (ECG)
      changes of the patients on a waiting list. The aim of this study was to assess
      clinical-technical performance and satisfaction with application of an
      international telephonic ECG system. A transnational telephonic ECG system was
      established between Lithuania and Germany. A follow-up study design was used to
      assess clinical-technical performance and user satisfaction with the system.
      According to inclusion and exclusion criteria, 34 patients were enrolled who
      transmitted 329 ECG's, of which 14 ECGs showed clinical changes. Of the ECGs sent
      254/329 (77%) were of good quality, 9 (3%) were of moderate quality, and 66 (20%)
      were of bad quality. Among physicians surveyed, 77.6% were satisfied or very
      satisfied with telemedicine services. A telecardiology service can help to
      identify patients with urgent problems requiring rapid assessment at the
      hospital. The service has high acceptance from physicians but needs to be
      improved in terms of technical performance and patient compliance expectations.

PMID- 18817500
TI  - Long-term future of telemedicine in Germany: the patient's, physician's, and
      payer's perspective.
AB  - While the near-term future of telemedicine development in Germany is quite clear,
      the long-term future has not been investigated. To determine telemedicine's long
      term future in Germany, in-depth interviews were conducted with 20 key decision
      makers in the German healthcare system. Interviewees included payers, doctors and
      their professional associations; and patients and their organizations. These
      individuals were asked what their expectations were in the application of
      telemedicine. According to the interviewees, several changes in the healthcare
      system as a whole will occur, which influence telemedicine. These include
      increase in cost pressure; the changing role of the payers and companies--as
      opposed to public organizations--playing a more active role in managing care.
      Physicians foresee more changes than payers do. Patients expect telemedicine to
      strengthen their role as patients. Most important telemedicine applications will
      be the "Gesundheitskarte" (a smart card enabling access to patient records),
      telemedicine as an enabling technology for other provider integration models,
      information systems for patients, and telemonitoring. The future looks promising
      for telemedicine in Germany.

PMID- 18817501
TI  - E-therapy for mental health problems: a systematic review.
AB  - The widespread availability of the Internet offers opportunities for improving
      access to therapy for people with mental health problems. There is a seemingly
      infinite supply of Internet-based interventions available on the World Wide Web.
      The aim of the present study is to systematically assess the methodological
      quality of randomized controlled trials (RCTs) concerning e-therapy for mental
      health problems. Two reviewers independently assessed the methodological quality
      of the RCTs, based on a list of criteria for the methodological quality
      assessment as recommended by the Cochrane Back Review Group. The search yielded
      14 papers that reported RCTs concerning e-therapy for mental-health problems. The
      methodological quality of studies included in this review was generally low. It
      is concluded that e-therapy may turn out to be an appropriate therapeutic entity,
      but the evidence needs to be more convincing. Recommendations are made concerning
      the method of reporting RCTs and the need to add some content items to an e
      therapy study.

PMID- 18817502
TI  - The study of a remote-controlled gastrointestinal drug delivery and sampling
      system.
AB  - A micromachined capsule based on microelectromechanical systems (MEMS) technology
      is introduced in this paper. It is an effective tool for diagnosing and treating
      gastrointestinal diseases. The microcapsule can carry out real-time drug release
      and the gastrointestinal fluid sampling in the gastrointestinal tract. According
      to the structural and metabolic characters of the gastrointestinal tract, the
      configuration of the microcapsule was designed as a cylinder. This nondigestible
      oral device can smoothly pass through the gastrointestinal tract for drug
      delivery and liquid sampling. The working mechanism of the capsule was the
      mechanic movement mode of a piston, which was regulated through a MEMS calorific
      element. The action of drug delivery and gastrointestinal fluid sampling in the
      gastrointestinal tract was performed wirelessly. The remote control device can be
      connected with a computer through a serial port (RS-232), and it can be used in
      telemedicine applications. Some experimental research has been carried out to
      validate the design. The experimental results indicated that the microcapsule can
      achieve drug delivery and liquid sample reliably.

PMID- 18817503
TI  - Clinical telehealth across the disciplines: lessons learned.
AB  - Videoconferencing technologies can vastly expand the reach of healthcare
      practitioners by providing patients (particularly those in rural/remote areas)
      with unprecedented access to services. While this represents a fundamental shift
      in the way that healthcare professionals care for their patients, very little is
      known about the impact of these technologies on clinical workflow practices and
      interprofessional collaboration. In order to better understand this, we have
      conducted a focused literature review, with the aim of providing policymakers,
      administrators, and healthcare professionals with an evidence-based foundation
      for decision-making. A total of 397 articles focused on videoconferencing in
      clinical contexts were retrieved, with 225 used to produce this literature
      review. Literature in the fields of medicine (including general and family
      practitioners and specialists in neurology, dermatology, radiology, orthopedics,
      rheumatology, surgery, cardiology, pediatrics, pathology, renal care, genetics,
      and psychiatry), nursing (including hospital-based, community-based, nursing
      homes, and home-based care), pharmacy, the rehabilitation sciences (including
      occupational and physical therapy), social work, and speech pathology were
      included in the review. Full utilization of the capacity of videoconferencing
      tools in clinical contexts requires some basic necessary technical conditions to
      be in place (including basic technological infrastructure, site-to-site
      technological compatibility, and available technical support). The available
      literature also elucidates key strategies for organizational readiness and
      technology adoption (including the development of a change management and user
      training plan, understanding program cost and remuneration issues, development of
      organizational protocols for system use, and strategies to promote
      interprofessional collaboration).

PMID- 18817504
TI  - Commentary on telephone medical consults.

PMID- 18817505
TI  - Controlling for severity of illness in outcome studies involving infectious
      diseases: impact of measurement at different time points.
AB  - BACKGROUND: Severity of illness is an important confounder in outcome studies
      involving infectious diseases. However, it is unclear whether the time at which
      severity of illness is measured is important. METHODS: We performed a
      retrospective study of 328 episodes of gram-negative bacteremia in adult patients
      to assess the impact of the time of measurement of severity of illness on the
      association between empirical antimicrobial therapy received and in-hospital
      mortality. Using a modified Acute Physiology Score (APS), severity of illness was
      measured at 2 time points: (1) hospital admission and (2) 24 hours before the
      first culture-positive blood sample was collected. Multivariate logistic
      regression was used to estimate the impact of adjusting for the APS on the
      relationship between empirical therapy received (ie, the exposure) and in
      hospital mortality (ie, the outcome). RESULTS: The mean APS (+/- standard
      deviation) of patients with bacteremia increased during their hospital stay (from
      19.2 +/- 11.6 at admission to 24.2 +/- 13.6 at the second time point; P < .01).
      When examining the association between empirical antimicrobial therapy received
      and in-hospital mortality, and controlling for the APS, there was a trend toward
      a decreased impact of appropriate therapy received on in-hospital mortality. The
      unadjusted odds ratio (OR) for the association between appropriate therapy
      received and in-hospital mortality was 0.83 (95% confidence interval [CI], 0.51
      1.34). After controlling for the APS at admission, this association was
      attenuated (OR, 0.94 [95% CI, 0.57-1.55]), and when a change in the APS was also
      included in the multivariate logistic regression model, the association was
      further attenuated (OR, 0.99 [95% CI, 0.58-1.69]). CONCLUSIONS: The magnitude of
      the association between appropriate antimicrobial therapy received and in
      hospital mortality among patients with gram-negative bacteremia was sensitive to
      the timing of adjustment for severity of illness.

PMID- 18817507
TI  - Conflict, convergent evolution, and the relative importance of immature and adult
      characters in endopterygote phylogenetics.
AB  - We use two episodes from systematic history to illustrate how conflict between
      immature and adult data was important for the development of phylogenetic
      systematics. A reference search in Zoological Record reveals that most
      phylogenetic analyses of endopterygote insects continue to utilize morphological
      rather than DNA sequence data. However, the use of immature and adult data is
      established for only a few taxa. An assessment of the phylogenetic utility of 73
      matrices with immature and adult data reveals that the immature partitions have
      fewer characters and that immature characters provide lower node support through
      homoplasy levels in immatures, and adult partitions are comparable. Despite much
      conflict, analyses based on all available evidence yield better tree resolution
      and higher support. We argue that DNA sequence-based matching of immature and
      adult stages will greatly help with the study of endopterygote immatures and
      facilitate the assembly of combined character matrices with data from all life
      history stages.

PMID- 18817508
TI  - Host-parasitoid associations in Strepsiptera.
AB  - Strepsiptera are obligate endoparasitoids that exhibit extreme sexual dimorphism
      and parasitize seven orders and 33 families of Insecta. The adult males and the
      first instar larvae in the Mengenillidia and Stylopidia are free-living, whereas
      the adult females in Mengenillidia are free-living but in the suborder Stylopidia
      they remain endoparasitic in the host. Parasitism occurs at the host
      larval/nymphal stage and continues in a mobile host until that host's adult
      stage. The life of the host is lengthened to allow the male strepsipteran to
      complete maturation and the viviparous female to release the first instar larvae
      when the next generation of the host's larvae/nymphs has been produced. The
      ability of strepsipterans to parasitize a wide range of hosts, in spite of being
      endoparasitoids, is perhaps due to their unique immune avoidance system. Aspects
      of virulence, heterotrophic heteronomy in the family Myrmecolacidae, cryptic
      species, genomics, immune response, and behavior of stylopized hosts are
      discussed in this chapter.

PMID- 18817506
TI  - MicroRNAs in cancer.
AB  - Within the past few years, studies on microRNA (miRNA) and cancer have burst onto
      the scene. Profiling of the miRNome (global miRNA expression levels) has become
      prevalent, and abundant miRNome data are currently available for various cancers.
      The pattern of miRNA expression can be correlated with cancer type, stage, and
      other clinical variables, so miRNA profiling can be used as a tool for cancer
      diagnosis and prognosis. miRNA expression analyses also suggest oncogenic (or
      tumor-suppressive) roles of miRNAs. miRNAs play roles in almost all aspects of
      cancer biology, such as proliferation, apoptosis, invasion/metastasis, and
      angiogenesis. Given that many miRNAs are deregulated in cancers but have not yet
      been further studied, it is expected that more miRNAs will emerge as players in
      the etiology and progression of cancer. Here we also discuss miRNAs as a tool for
      cancer therapy.

PMID- 18817509
TI  - A study in inspiration: Charles Henry Turner (1867--1923) and the investigation
      of insect behavior.
AB  - Charles Henry Turner was an African American scientist who, while eking out a
      living as a high school science teacher, made important advances in the study of
      insect learning and behavior. Contributions include the development of research
      methods, investigations of color vision and pattern vision in honey bees, and the
      first demonstration of Pavlovian conditioning in an insect. This review begins
      with a biography and continues with a summary of his major research
      accomplishments. Also included are quotations from his publications and from
      people who knew him. In addition, the question is raised as to why Turner did not
      receive an academic appointment, and similar data of racial disparity are
      presented on the small number of African American entomologists. It is suggested
      that the story of Turner can be used to increase interest in entomology,
      especially among African Americans.

PMID- 18817510
TI  - Structural biology of shared cytokine receptors.
AB  - Recent structural information for complexes of cytokine receptor ectodomains
      bound to their ligands has significantly expanded our understanding of the
      macromolecular topology and ligand recognition mechanisms used by our three
      principal shared cytokine signaling receptors-gp130, gamma(c), and beta(c). The
      gp130 family receptors intricately coordinate three structurally unique cytokine
      binding sites on their four-helix bundle cytokine ligands to assemble multimeric
      signaling complexes. These organizing principles serve as topological blueprints
      for the entire gp130 family of cytokines. Novel structures of gamma(c) and
      beta(c) complexes show us new twists, such as the use of a nonstandard sushi-type
      alpha receptors for IL-2 and IL-15 in assembling quaternary gamma(c) signaling
      complexes and an antiparallel interlocked dimer in the GM-CSF signaling complex
      with beta(c). Unlike gp130, which appears to recognize vastly different cytokine
      surfaces in chemically unique fashions for each ligand, the gamma(c)-dependent
      cytokines appear to seek out some semblance of a knobs-in-holes shape recognition
      code in order to engage gamma(c) in related fashions. We discuss the structural
      similarities and differences between these three shared cytokine receptors, as
      well as the implications for transmembrane signaling.

PMID- 18817511
TI  - Complementary roles of the main and accessory olfactory systems in mammalian mate
      recognition.
AB  - We review studies conducted in mouse and ferret that have specified roles of both
      the main and the accessory olfactory nervous systems in the detection and
      processing of body odorants (e.g., urinary pheromones, extraorbital lacrimal
      gland secretions, major histocompatibility complex peptide ligands, and anal
      scent gland secretions) that play an essential role in sex discrimination and
      attraction between males and females leading to mate choice and successful
      reproduction. We also review literature that compares the forebrain processing of
      inputs from the two olfactory systems in the two sexes that underlies
      heterosexual partner preferences. Finally, we review experiments that raise the
      possibility that body odorants detected by the main olfactory system contribute
      to mate recognition in humans.

PMID- 18817512
TI  - Role of HDAC2 in the pathophysiology of COPD.
AB  - Chronic obstructive pulmonary disease (COPD), characterized by progressive
      inflammation in the small airways and lung parenchyma, is mediated by the
      increased expression of multiple inflammatory genes. The increased expression of
      these genes is regulated by acetylation of core histones, whereas histone
      deacetylase 2 (HDAC2) suppresses inflammatory gene expression. In COPD, HDAC2
      activity and expression are reduced in peripheral lung and in alveolar
      macrophages, resulting in amplification of the inflammatory response.
      Corticosteroid resistance in COPD occurs because corticosteroids use HDAC2 to
      switch off activated inflammatory genes. The reduction in HDAC2 appears to be
      secondary to the increased oxidative and nitrative stress in COPD lungs.
      Antioxidants and inhibitors of nitric oxide synthesis may therefore restore
      corticosteroid sensitivity in COPD, but this can also be achieved by low
      concentrations of theophylline and curcumin, which act as HDAC activators.

PMID- 18817513
TI  - Novel drug delivery systems for inner ear protection and regeneration after
      hearing loss.
AB  - BACKGROUND: A cochlear implant, the only current treatment for restoring auditory
      perception after severe or profound sensorineural hearing loss (SNHL), works by
      electrically stimulating spiral ganglion neurons (SGNs). However, gradual
      degeneration of SGNs associated with SNHL can compromise the efficacy of the
      device. OBJECTIVE: To review novel drug delivery systems for preserving and/or
      regenerating sensory cells in the cochlea after SNHL. METHODS: The effectiveness
      of traditional cochlear drug delivery systems is compared to newer techniques
      such as cell, polymer and gene transfer technologies. Special requirements for
      local drug delivery to the cochlea are discussed, such as protecting residual
      hearing and site-specific drug delivery for cell preservation and regeneration.
      RESULTS/CONCLUSIONS: Drug delivery systems with the potential for immediate
      clinical translation, as well as those that will contribute to the future of
      hearing preservation or cochlear cellular regeneration, are identified.

PMID- 18817514
TI  - Thermo-responsive systems for controlled drug delivery.
AB  - Controlled drug delivery systems represent advanced systems that can be tightly
      modulated by stimuli in order to treat diseases in which sustained drug release
      is undesirable. Among the many different stimuli-sensitive delivery systems,
      temperature-sensitive drug delivery systems offer great potential over their
      counterparts due to their versatility in design, tunability of phase transition
      temperatures, passive targeting ability and in situ phase transitions. Thus,
      thermosensitive drug delivery systems can overcome many of the hurdles of
      conventional drug delivery systems in order to increase drug efficacies, drug
      targeting and decrease drug toxicities. In an effort to further control existing
      temperature-responsive systems, current innovative applications have combined
      temperature with other stimuli such as pH and light. The result has been the
      development of highly sophisticated systems, which demonstrate exquisite control
      over drug release and represent huge advances in biomedical research.

PMID- 18817515
TI  - Enhanced composite electrospun nanofiber scaffolds for use in drug delivery.
AB  - The utility of nanofibrous electrospun composite scaffolds has greatly expanded
      over the last decade, so that they now serve as viable drug delivery vehicles for
      a host of different biomedical applications. The material properties of
      electrospun scaffolds are extremely advantageous for drug delivery, in which site
      specificity and lower overall medicinal dosages lead to a potential industry
      altering mechanism of delivering therapeutics. Different drugs used to
      predominantly treat infections and cancers can easily be incorporated and
      released at therapeutic dosages. Further, the inherent high porosity of these
      electrospun scaffolds allows for a more precisely controlled degradation which is
      tunable by polymer composition and fiber morphology, leading to sustained drug
      release. This review examines the current research and breakthrough discoveries
      that have elevated electrospun scaffolds to a cutting-edge technology that will
      dramatically alter the landscape of drug delivery.

PMID- 18817516
TI  - Applications of ultrasonic skin permeation in transdermal drug delivery.
AB  - Transdermal ultrasound-mediated drug delivery has been studied as a method for
      needle-less, non-invasive drug administration. Potential obstacles include the
      stratum corneum, which is not sufficiently passively permeable to allow effective
      transfer of many medications into the bloodstream without active methods. A
      general review of the transdermal ultrasound drug delivery literature has shown
      that this technology offers promising potential for non-invasive drug
      administration. Included in this review are the reported acoustic parameters used
      for achieving delivery, along with the known intensities and exposure times.
      Ultrasound mechanisms are discussed as well as spatial field characteristics.
      Accurate and precise quantification of the acoustic field used in drug delivery
      experiments is essential to ensure safety versus efficacy and to avoid
      potentially harmful bioeffects.

PMID- 18817517
TI  - Ultrasound targeted microbubble destruction for drug and gene delivery.
AB  - BACKGROUND: Gas-filled microbubbles have been used as ultrasound contrast agents
      for some decades. More recently, such microbubbles have evolved as experimental
      tools for organ- and tissue-specific drug and gene delivery. When sonified with
      ultrasound near their resonance frequency, microbubbles oscillate. With higher
      ultrasound energies, oscillation amplitudes increase, leading to microbubble
      destruction. This phenomenon can be used to deliver a substance into a target
      organ, if microbubbles are co-administered loaded with drugs or gene therapy
      vectors before i.v. injection. OBJECTIVE: This review focuses on different
      experimental applications of microbubbles as tools for drug and gene delivery.
      Different organ systems and different classes of bioactive substances that have
      been used in previous studies will be discussed. METHODS: All the available
      literature was reviewed to highlight the potential of this non-invasive, organ
      specific delivery system. CONCLUSION: Ultrasound targeted microbubble destruction
      has been used in various organ systems and in tumours to successfully deliver
      drugs, proteins, gene therapy vectors and gene silencing constructs. Many proof
      of principle studies have demonstrated its potential as a non-invasive delivery
      tool. However, too few large animal studies and studies with therapeutic aims
      have been performed to see a clinical application of this technique in the near
      future. Nevertheless, there is great hope that preclinical large animal studies
      will confirm the successful results already obtained in small animals.

PMID- 18817518
TI  - Vaccines against epidemic and pandemic influenza.
AB  - BACKGROUND: Preventative vaccination is the most effective way to control
      epidemic and, perhaps, pandemic influenza viral infections. However, the
      immunogenicity and efficacy of influenza vaccines against epidemic strains are
      suboptimal among older adults. The risk of serious complications from influenza
      viral infection is compounded by co-morbid conditions among older adults.
      Furthermore, despite annual influenza vaccination campaigns, the vaccination
      rates in high risk populations range from 60.5 - 79.2% only [1] . In addition,
      H5N1 avian influenza viruses have the potential to cause a pandemic. However,
      H5N1 vaccines currently licensed in the US are poorly immunogenic in high doses
      in the absence of an adjuvant even in healthy adults. OBJECTIVES: In this review,
      we address the current status of vaccines against epidemic and avian influenza
      viruses of pandemic potential. METHODS: We have limited the review to the
      discussion of technologies and strategies that have progressed to human clinical
      trials and/or licensure for seasonal and pandemic influenza. RESULTS/CONCLUSION:
      Improving the immunogenicity of vaccines against avian influenza viruses, as well
      as aggressive programs to vaccinate high risk populations against seasonal and
      pandemic influenza, are crucial for our public health efforts in minimizing the
      impact of influenza epidemics or pandemics.

PMID- 18817519
TI  - From nose to brain: understanding transport capacity and transport rate of drugs.
AB  - The unique relationship between nasal cavity and cranial cavity tissues in
      anatomy and physiology makes intranasal delivery to the brain feasible. An
      intranasal delivery provides some drugs with short channels to bypass the blood
      brain barrier (BBB), especially for those with fairly low brain concentrations
      after a routine delivery, thus greatly enhancing the therapeutic effect on brain
      diseases. In the past two decades, a good number of encouraging outcomes have
      been reported in the treatment of diseases of the brain or central nervous system
      (CNS) through nasal administration. In spite of the significant merit of
      bypassing the BBB, direct nose-to-brain delivery still bears the problems of low
      efficiency and volume for capacity due to the limited volume of the nasal cavity,
      the small area ratio of olfactory mucosa to nasal mucosa and the limitations of
      low dose and short retention time of drug absorption. It is crucial that
      selective distribution and retention time of drugs or preparations on olfactory
      mucosa should be enhanced so as to increase the direct delivery efficiency. In
      this article, we first briefly review the nose-to-brain transport pathways,
      before detailing the impacts on them, followed by a comprehensive summary of
      effective methods, including formulation modification, agglutinant-mediated
      transport and a brain-homing, peptide-mediated delivery based on phage display
      screening technique, with a view to providing a theoretic reference for elevating
      the therapeutic effects on brain diseases.

PMID- 18817520
TI  - A chimaeric glutamyl:glutaminyl-tRNA synthetase: implications for evolution.
AB  - aaRSs (aminoacyl-tRNA synthetases) are multi-domain proteins that have evolved by
      domain acquisition. The anti-codon binding domain was added to the more ancient
      catalytic domain during aaRS evolution. Unlike in eukaryotes, the anti-codon
      binding domains of GluRS (glutamyl-tRNA synthetase) and GlnRS (glutaminyl-tRNA
      synthetase) in bacteria are structurally distinct. This originates from the
      unique evolutionary history of GlnRSs. Starting from the catalytic domain,
      eukaryotic GluRS evolved by acquiring the archaea/eukaryote-specific anti-codon
      binding domain after branching away from the eubacteria family. Subsequently,
      eukaryotic GlnRS evolved from GluRS by gene duplication and horizontally
      transferred to bacteria. In order to study the properties of the putative
      ancestral GluRS in eukaryotes, formed immediately after acquiring the anti-codon
      binding domain, we have designed and constructed a chimaeric protein, cGluGlnRS,
      consisting of the catalytic domain, Ec GluRS (Escherichia coli GluRS), and the
      anti-codon binding domain of EcGlnRS (E. coli GlnRS). In contrast to the isolated
      EcN-GluRS, cGluGlnRS showed detectable activity of glutamylation of E. coli
      tRNA(glu) and was capable of complementing an E. coli ts (temperature-sensitive)
      GluRS strain at non-permissive temperatures. Both cGluGlnRS and EcN-GluRS were
      found to bind E. coli tRNA(glu) with native EcGluRS-like affinity, suggesting
      that the anticodon-binding domain in cGluGlnRS enhances k(cat) for glutamylation.
      This was further confirmed from similar experiments with a chimaera between EcN
      GluRS and the substrate-binding domain of EcDnaK (E. coli DnaK). We also show
      that an extended loop, present in the anticodon-binding domains of GlnRSs, is
      absent in archaeal GluRS, suggesting that the loop was a later addition,
      generating additional anti-codon discrimination capability in GlnRS as it evolved
      from GluRS in eukaryotes.

PMID- 18817521
TI  - Functional replacement of a retroviral late domain by ubiquitin fusion.
AB  - Retroviral Gag polyprotein precursors are both necessary and sufficient for the
      assembly and release of virus-like particles (VLPs) from infected cells. It is
      well established that small Gag-encoded motifs, known as late domains, promote
      particle release by interacting with components of the cellular endosomal sorting
      and ubiquitination machinery. The Gag proteins of a number of different
      retroviruses are ubiquitinated; however, the role of Gag ubiquitination in
      particle egress remains undefined. In this study, we investigated this question
      by using a panel of equine infectious anemia virus (EIAV) Gag derivatives bearing
      the wild-type EIAV late domain, heterologous retroviral late domains or no late
      domain. Ubiquitin was fused in cis to the C-termini of these Gag polyproteins,
      and the effects on VLP budding were measured. Remarkably, fusion of ubiquitin to
      EIAV Gag lacking a late domain (EIAV/DeltaYPDL-Ub) largely rescued VLP release.
      We also determined the effects of ubiquitin fusion on the sensitivity of particle
      release to budding inhibitors and to depletion of key endosomal sorting factors.
      Ubiquitin fusion rendered EIAV/DeltaYPDL-Ub sensitive to depletion of cellular
      endosomal sorting factors Tsg101 and Alix and to overexpression of dominant
      negative fragments of Tsg101 and Alix. These findings demonstrate that ubiquitin
      can functionally compensate for the absence of a retroviral late domain and
      provide insights into the host-cell machinery engaged by ubiquitin during
      particle egress.

PMID- 18817522
TI  - High data output and automated 3D correlative light-electron microscopy method.
AB  - Correlative light/electron microscopy (CLEM) allows the simultaneous observation
      of a given subcellular structure by fluorescence light microscopy (FLM) and
      electron microscopy. The use of this approach is becoming increasingly frequent
      in cell biology. In this study, we report on a new high data output CLEM method
      based on the use of cryosections. We successfully applied the method to analyze
      the structure of rough and smooth Russell bodies used as model systems. The major
      advantages of our method are (i) the possibility to correlate several hundreds of
      events at the same time, (ii) the possibility to perform three-dimensional (3D)
      correlation, (iii) the possibility to immunolabel both endogenous and
      recombinantly expressed proteins at the same time and (iv) the possibility to
      combine the high data analysis capability of FLM with the high precision-accuracy
      of transmission electron microscopy in a CLEM hybrid morphometry analysis. We
      have identified and optimized critical steps in sample preparation, defined
      routines for sample analysis and retracing of regions of interest, developed
      software for semi/fully automatic 3D reconstruction and defined preliminary
      conditions for an hybrid light/electron microscopy morphometry approach.

PMID- 18817523
TI  - Palmitoylation controls recycling in lysosomal sorting and trafficking.
AB  - For the efficient trafficking of lysosomal proteins, the cationic-dependent and 
      independent mannose 6-phosphate receptors and sortilin must bind cargo in the
      Golgi apparatus, be packaged into clathrin-coated trafficking vesicles and
      traffic to the endosomes. Once in the endosomes, the receptors release their
      cargo into the endosomal lumen and recycle back to the Golgi for another round of
      trafficking, a process that requires retromer. In this study, we demonstrate that
      palmitoylation is required for the efficient retrograde trafficking of sortilin,
      and the cationic-independent mannose 6-phosphate as palmitoylation-deficient
      receptors remain trapped in the endosomes. Importantly, we also show that
      palmitoylation is required for receptor interaction with retromer as
      nonpalmitoylated receptor did not interact with retromer. In addition, we have
      identified DHHC-15 as the palmitoyltransferase responsible for this modification.
      In summary, we have shown the functional significance of palmitoylation in
      lysosomal receptor sorting and trafficking.

PMID- 18817524
TI  - Kinesin-1 (uKHC/KIF5B) is required for bidirectional motility of ER exit sites
      and efficient ER-to-Golgi transport.
AB  - Transport of proteins and lipids between intracellular compartments is
      fundamental to the organization and function of eukaryotic cells. The efficiency
      of this process is greatly enhanced through coupling of membranes to
      microtubules. This serves two functions, organelle positioning and vesicular
      transport. In this study, we show that in addition to the well-known role for the
      minus-end motor dynein in endoplasmic reticulum (ER)-to-Golgi transport, the plus
      end-directed motor kinesin-1 is involved in positioning coat protein II-coated ER
      exit sites (ERES) in cells as well as the formation of transport carriers and
      their movement to the Golgi. Using two-dimensional Gaussian fitting to determine
      their location at high spatial resolution, we show that ERES undergo short-range
      bidirectional movements. Bidirectionality depends on both kinesin-1 and dynein.
      Suppression of kinesin-1 (KIF5B) also inhibits ER-to-Golgi transport and affects
      the morphology of ER-to-Golgi transport carriers. Furthermore, we show that
      suppression of dynein heavy chain expression increases the range of movement of
      ERES, suggesting that dynein might anchor ERES, or the ER itself, to
      microtubules. These data implicate kinesin-1 in the spatial organization of the
      ER/Golgi interface as well as in traffic outside the ER.

PMID- 18817525
TI  - Loss of the Batten disease gene CLN3 prevents exit from the TGN of the mannose 6
      phosphate receptor.
AB  - The neuronal ceroid lipofuscinoses (NCLs, Batten disease) are a group of
      inherited childhood-onset neurodegenerative disorders characterized by the
      lysosomal accumulation of undigested material within cells. To understand this
      dysfunction, we analysed trafficking of the cation-independent mannose 6
      phosphate receptor (CI-MPR), which delivers the digestive enzymes to lysosomes. A
      common form of NCL is caused by mutations in CLN3, a multipass transmembrane
      protein of unknown function. We report that ablation of CLN3 causes accumulation
      of CI-MPR in the trans Golgi network, reflecting a 50% reduction in exit. This CI
      MPR trafficking defect is accompanied by a fall in maturation and cellular
      activity of lysosomal cathepsins. CLN3 is therefore essential for trafficking
      along the route needed for delivery of lysosomal enzymes, and its loss thereby
      contributes to and may explain the lysosomal dysfunction underlying Batten
      disease.

PMID- 18817526
TI  - Gyrating clathrin: highly dynamic clathrin structures involved in rapid receptor
      recycling.
AB  - We report here detection of novel intracellular clathrin-coated structures
      revealed by continuous high-speed imaging of cells expressing green fluorescent
      protein fusion proteins. These structures, which we operationally term 'gyrating
      clathrin' (G-clathrin), are characterized by localized but extremely rapid
      movement, leading to the hypothesis that they are coated buds on waving membrane
      tubules. G-clathrin structures have structurally and functionally distinct
      features. They lack detectable adaptor proteins AP-1 and AP-2 but contain GGA1
      [Golgi-localized, gamma-ear-containing, Arf (ADP-ribosylation factor)-binding
      protein] as well as the cation-dependent mannose-6-phosphate receptor. While they
      accumulate internalized transferrin (Tf), they do not contain detectable levels
      of cargos targeted for the late endosome/lysosome pathway such as EGF and
      dextran. Pulse-chase studies indicate that Tf appears in G-clathrin structures in
      the cell periphery after sorting endosomes (SEs), but before filling of the
      perinuclear endocytic recycling compartment. Furthermore, the inhibitors LY294002
      and wortmannin, which inhibit direct recycling of Tf from SEs to the plasma
      membrane, also block its appearance in G-clathrin. These observations suggest
      that peripheral G-clathrin contributes to rapid recycling, a kinetically defined
      compartment that has largely eluded structural identification. More generally,
      the rapid continuous live cell imaging reported here reveals new aspects of
      membrane trafficking.

PMID- 18817527
TI  - Dynamic remodeling of the endosomal system during formation of Salmonella-induced
      filaments by intracellular Salmonella enterica.
AB  - The infection by Salmonella enterica results in the massive remodeling of the
      endosomal system of eukaryotic host cells. One unique consequence is the
      formation of long tubular endosomal compartments, so-called Salmonella-induced
      filaments (SIF). Formation of SIF requires the function of type III secretion
      system and is a requirement of efficient intracellular proliferation of
      Salmonella. Using high-resolution live cell imaging approaches and electron
      microscopy, we report for the first time the highly dynamic characteristics of
      SIF and their ultrastructural properties. In the early phase of infection (4-5
      h), SIF display highly dynamic properties in various types of host cells. SIF
      extend, branch and contract rapidly, and a stabilized network of SIF is formed
      later (>or=8 h after infection). The velocities of SIF extension and contraction
      in the different phases of infection were quantified. Our observations lead to
      novel models for the modification of host cell transport processes by virulence
      factors of intracellular Salmonella.

PMID- 18817528
TI  - Nuclear export signal consensus sequences defined using a localization-based
      yeast selection system.
AB  - Proteins bearing nuclear export signals (NESs) are translocated to the cytoplasm
      from the nucleus mainly through the CRM1-dependent pathway. However, the NES
      consensus sequence remains poorly defined, and there are currently no high
      throughput methods for identifying NESs. In this study, we report the development
      of an efficient yeast selection system for detecting nuclear export activity as
      well as several reliable NES consensus sequences identified using this method.
      Our selection system is based on the nuclear export-dependent rescue of Tys1p, an
      essential cytoplasmic protein that has been artificially localized to the nucleus
      in a haploid Delta tys1 knockout strain. A screen of a random peptide library
      revealed 101 distinct CRM1-dependent NESs, which were classified into six
      patterns according to the conserved hydrophobic spacing. By combining mutational
      analyses, we have defined new NES consensus sequences with more specific and
      redundant residues than the traditional consensus sequence, which are consistent
      with most experimentally confirmed NESs. These NES consensus sequences should
      help identify functional NESs, and our selection system can be used to identify
      other targeting signals or proteins imported to specific subcellular
      compartments.

PMID- 18817529
TI  - The ESCRT-I subunit TSG101 controls endosome-to-cytosol release of viral RNA.
AB  - Like other enveloped viruses, vesicular stomatitis virus infects cells through
      endosomes. There, the viral envelope undergoes fusion with endosomal membranes,
      thereby releasing the nucleocapsid into the cytoplasm and allowing infection to
      proceed. Previously, we reported that the viral envelope fuses preferentially
      with the membrane of vesicles present within multivesicular endosomes. Then,
      these intra-endosomal vesicles (containing nucleocapsids) are transported to late
      endosomes, where back-fusion with the endosome limiting membrane delivers the
      nucleocapsid into the cytoplasm. In this study, we show that the tumor
      susceptibility gene 101 (Tsg101) subunit of the endosomal sorting complexes
      required for transport (ESCRT)-I complex, which mediates receptor sorting into
      multivesicular endosomes, is dispensable for viral envelope fusion with endosomal
      membranes and viral RNA transport to late endosomes but is necessary for
      infection. Our data indicate that Tsg101, in contrast to the ESCRT-0 component
      Hrs, plays a direct role in nucleocapsid release from within multivesicular
      endosomes to the cytoplasm, presumably by controlling the back-fusion process. We
      conclude that Tsg101, through selective interactions with its partners including
      Hrs and Alix, may link receptor sorting and lysosome targeting to the back-fusion
      process involved in viral capsid release.

PMID- 18817530
TI  - Minimization of immunosuppression after lung transplantation: current trends.
AB  - This paper reviews efforts that have been made to minimize immunosuppression in
      lung transplant patients. A brief history of tolerance and its potential
      application to lung transplantation is also discussed.

PMID- 18817531
TI  - Sarcoids in two captive tapirs (Tapirus bairdii): clinical, pathological and
      molecular study.
AB  - This case report describes for the first time sarcoids in tapirs (Tapirus
      bairdii), namely, a 2-year-old male and a 3.6-year-old female born and housed at
      the same facility. The male presented with a 3-cm nodular, red, pedunculated,
      hairless, ulcerated mass on the inner surface of the left pinna. No recurrence or
      additional growths were present during the 3 years following surgical excision of
      the mass. The female presented with a similar 2-cm mass on the inner surface of
      the right pinna, which recurred 2 months following surgical excision, but was
      subsequently successfully treated locally with liquid nitrogen with no further
      recurrence during a 2-year follow-up period. Histologically, these two masses
      closely resembled equine sarcoids. Similarly, an association with bovine
      papillomavirus 1 was demonstrated using polymerase chain reaction and in situ
      hybridization.

PMID- 18817532
TI  - Caritas--caring as an ethical conduct.
AB  - The aim of this theoretical study is to describe and analyze caritas by seeking
      the primary source for this phenomenon, which is used as a central motive in
      Eriksson's Caritative Theory. The search for the origin and the essence of
      caritas by critical analysis will create an opportunity to assimilate new meaning
      into the practice of caring science. This new meaning, based on interpretation,
      will also act as a solid base for the creation of future theories within caring
      science. Although this study does not intend to create a new theory for this
      domain, an attempt is made to shed light on new understandings to establish a
      deeper foundation for further discussion. Therefore, the methodological basis
      used is the hermeneutics phenomenology described by Nygren. The starting points
      refer to three basic assumptions, the former two of which present the core of
      caring science as an academic discipline; the latter borrows from philosophical
      creation theology. Therefore, the path for analyzing caritas and the significance
      of developing a deeper and meaningful understanding are based on the writing of
      Eriksson as well as through historical and philosophical sources from Judaism,
      such as the Bible and the Talmud. The results of this study have introduced a new
      meaning and created a 'space' for caritas. These results are related to the
      notion of attitudes, being driven by curiosity and questioning, that link faith
      and scientific investigation. Above all, these attitudes form a central motive
      profoundly linked to love. Hence, caritas as an attitude turns the concept of
      care into a more ethical act. However, these new understandings have given rise
      to ethical questions that obligate consideration towards further study.

PMID- 18817533
TI  - Presenting and exploring biological pathways with PathVisio.
AB  - BACKGROUND: Biological pathways are a useful abstraction of biological concepts,
      and software tools to deal with pathway diagrams can help biological research.
      PathVisio is a new visualization tool for biological pathways that mimics the
      popular GenMAPP tool with a completely new Java implementation that allows better
      integration with other open source projects. The GenMAPP MAPP file format is
      replaced by GPML, a new XML file format that provides seamless exchange of
      graphical pathway information among multiple programs. RESULTS: PathVisio can be
      combined with other bioinformatics tools to open up three possible uses: visual
      compilation of biological knowledge, interpretation of high-throughput expression
      datasets, and computational augmentation of pathways with interaction
      information. PathVisio is open source software and available at
      http://www.pathvisio.org. CONCLUSION: PathVisio is a graphical editor for
      biological pathways, with flexibility and ease of use as primary goals.

PMID- 18817534
TI  - Twenty-four hours secretion pattern of serum estradiol in healthy prepubertal and
      pubertal boys as determined by a validated ultra-sensitive extraction RIA.
AB  - BACKGROUND: The role of estrogens in male physiology has become evident. However,
      clinically useful normative data for estradiol secretion in boys has not
      previously been established due to the insensitivity of current methods used in
      clinical routine. By use of a validated ultra-sensitive extraction RIA, our aim
      was to establish normative data from a group consisting of healthy boys in
      prepuberty and during pubertal development. METHODS: Sixty-two 24-hours serum
      profiles (6 samples/24 hours) were obtained from 44 healthy boys (ages; 7.2-18.6
      years) during their pubertal development, classified into five stages: prepuberty
      (testis, 1-2 mL), early (testis, 3-6 mL), mid (testis, 8-12 mL), late-1
      (testis,15-25 mL, not reached final height) and late-2 (testis,15-25 mL, reached
      final height). Serum estradiol was determined by an ultra- sensitive extraction
      radioimmunoassay with detection limit 4 pmol/L and functional sensitivity 6
      pmol/L. RESULTS: Mean estradiol concentrations during 24-hours secretion
      increased from prepuberty (median: <4 (5-95 percentiles: <4 - 7) pmol/L) to early
      puberty (6 (<4 - 12 pmol/L) but then remained relatively constant until a marked
      increase between mid-puberty (8 (4 - 17) pmol/L) and late-1 (21 (12 - 37) pmol/L)
      puberty, followed by a slower increase until late-2 puberty (32 (20 - 47)
      pmol/L). The diurnal rhythm of serum estradiol was non-measurable in pre- and
      early puberty, but discerned in mid-puberty, and become evident in late pubertal
      stages with peak values at 0600 to 1000 h. CONCLUSION: With the use of an ultra
      sensitive extraction RIA, we have provided clinically useful normative data for
      estradiol secretion in boys.

PMID- 18817535
TI  - Antioxidant activities and phenolic contents of the methanol extracts of the
      stems of Acokanthera oppositifolia and Adenia gummifera.
AB  - BACKGROUND: Acokanthera oppositifolia Lam (family: Apocynaceae) is a shrub or
      small tree with white latex, and the leaves of this plant are used in the form of
      a snuff to treat headaches and in infusions for abdominal pains and convulsions
      and septicaemia. Adenia gummifera Harv of the family Passifloraceae is a
      distinctive woody climber whose infusions are used as emetics and are said to
      help with some forms of depression. Lipid peroxidation has gained more importance
      today because of its involvement in pathogenesis of many diseases. Free radicals
      are the main agents in lipid peroxidation. Antioxidants thus play an important
      role of protecting the human body against damage by the free radicals. Plants
      containing phenolic compounds have been reported to possess strong antioxidant
      properties. METHODS: The antioxidant activities and phenolic contents of the
      methanol extracts of the stems of Acokanthera oppositifolia and Adenia gummifera
      were evaluated using in vitro standard procedures. Spectrophotometry was the
      basis for the determinations of total phenol, total flavonoids, flavonols, and
      proanthocyanidins. Tannins, quercetin and catechin equivalents were used for
      these parameters. The antioxidant activities of the stem extract of Acokanthera
      oppositifolia were determined by the 2,2'-azinobis-3- ethylbenzothiazoline-6
      sulfonic acid (ABTS), 1,1-Diphenyl-2-picrylhydrazyl (DPPH), and ferrous reducing
      antioxidant property (FRAP) methods. RESULTS: The results from this study showed
      that the antioxidant activities of the stem extract of Acokanthera oppositifolia
      as determined by the 1,1-Diphenyl-2-picrylhydrazyl (DPPH), and ferrous reducing
      antioxidant property (FRAP) methods, were higher than that of Adenia gummifera.
      The levels of total phenols and flavonols for A. oppositifolia were also higher.
      On the other hand, the stem extract of Adenia gummifera had higher level of total
      flavonoids and proanthocyanidins than that of Acokanthera oppositifolia. The 2,
      2'-azinobis-3- ethylbenzothiazoline-6-sulfonic acid (ABTS) activities of the 2
      plant extracts were similar and comparable to that of BHT. CONCLUSION: Thus, the
      present results indicate clearly that the extracts of Acokanthera oppositifolia
      and Adenia gummifera possess antioxidant properties and could serve as free
      radical inhibitors or scavengers, acting possibly as primary antioxidants. This
      study has to some extent validated the medicinal potential of the stems of
      Acokanthera oppositifolia and Adenia gummifera.

PMID- 18817536
TI  - A three-country comparison of psychotropic medication prevalence in youth.
AB  - BACKGROUND: The study aims to compare cross-national prevalence of psychotropic
      medication use in youth. METHODS: A population-based analysis of psychotropic
      medication use based on administrative claims data for the year 2000 was
      undertaken for insured enrollees from 3 countries in relation to age group (0-4,
      5-9, 10-14, and 15-19), gender, drug subclass pattern and concomitant use. The
      data include insured youth aged 0-19 in the year 2000 from the Netherlands (n =
      110,944), Germany (n = 356,520) and the United States (n = 127,157). RESULTS: The
      annual prevalence of any psychotropic medication in youth was significantly
      greater in the US (6.7%) than in the Netherlands (2.9%) and in Germany (2.0%).
      Antidepressant and stimulant prevalence were 3 or more times greater in the US
      than in the Netherlands and Germany, while antipsychotic prevalence was 1.5-2.2
      times greater. The atypical antipsychotic subclass represented only 5% of
      antipsychotic use in Germany, but 48% in the Netherlands and 66% in the US. The
      less commonly used drugs e.g. alpha agonists, lithium and antiparkinsonian agents
      generally followed the ranking of US>Dutch>German youth with very rare (less than
      0.05%) use in Dutch and German youth. Though rarely used, anxiolytics were twice
      as common in Dutch as in US and German youth. Prescription hypnotics were half as
      common as anxiolytics in Dutch and US youth and were very uncommon in German
      youth. Concomitant drug use applied to 19.2% of US youth which was more than
      double the Dutch use and three times that of German youth. CONCLUSION: Prominent
      differences in psychotropic medication treatment patterns exist between youth in
      the US and Western Europe and within Western Europe. Differences in policies
      regarding direct to consumer drug advertising, government regulatory
      restrictions, reimbursement policies, diagnostic classification systems, and
      cultural beliefs regarding the role of medication for emotional and behavioral
      treatment are likely to account for these differences.

PMID- 18817537
TI  - Predicting the sensitivity and specificity of published real-time PCR assays.
AB  - BACKGROUND: In recent years real-time PCR has become a leading technique for
      nucleic acid detection and quantification. These assays have the potential to
      greatly enhance efficiency in the clinical laboratory. Choice of primer and probe
      sequences is critical for accurate diagnosis in the clinic, yet current
      primer/probe signature design strategies are limited, and signature evaluation
      methods are lacking. METHODS: We assessed the quality of a signature by
      predicting the number of true positive, false positive and false negative hits
      against all available public sequence data. We found real-time PCR signatures
      described in recent literature and used a BLAST search based approach to collect
      all hits to the primer-probe combinations that should be amplified by real-time
      PCR chemistry. We then compared our hits with the sequences in the NCBI taxonomy
      tree that the signature was designed to detect. RESULTS: We found that many
      published signatures have high specificity (almost no false positives) but low
      sensitivity (high false negative rate). Where high sensitivity is needed, we
      offer a revised methodology for signature design which may designate that
      multiple signatures are required to detect all sequenced strains. We use this
      methodology to produce new signatures that are predicted to have higher
      sensitivity and specificity. CONCLUSION: We show that current methods for real
      time PCR assay design have unacceptably low sensitivities for most clinical
      applications. Additionally, as new sequence data becomes available, old assays
      must be reassessed and redesigned. A standard protocol for both generating and
      assessing the quality of these assays is therefore of great value. Real-time PCR
      has the capacity to greatly improve clinical diagnostics. The improved assay
      design and evaluation methods presented herein will expedite adoption of this
      technique in the clinical lab.

PMID- 18817538
TI  - The signature of long-standing balancing selection at the human defensin beta-1
      promoter.
AB  - BACKGROUND: Defensins, small endogenous peptides with antimicrobial activity, are
      pivotal components of the innate immune response. A large cluster of defensin
      genes is located on human chromosome 8p; among them the beta defensin 1 (DEFB1)
      promoterhas been extensively studied since discovery that specific polymorphisms
      and haplotypes associate with asthma and atopy, susceptibility to severe sepsis,
      as well as HIV and Candida infection predisposition. RESULTS: Here, we
      characterize the sequence variation and haplotype structure of the DEFB1 promoter
      region in six human populations. In all of them, we observed high levels of
      nucleotide variation, an excess of intermediate-frequency alleles, reduced
      population differentiation and a genealogy with common haplotypes separated by
      deep branches. Indeed, a significant departure from the expectation of
      evolutionary neutrality was observed in all populations and the possibility that
      this is due to demographic history alone was ruled out. Also, we verified that
      the selection signature is restricted to the promoter region and not due to a
      linked balanced polymorphism. A phylogeny-based estimation indicated that the two
      major haplotype clades separated around 4.5 million years ago, approximately the
      time when the human and chimpanzee lineages split. CONCLUSION: Altogether, these
      features represent strong molecular signatures of long-term balancing selection,
      a process that is thought to be extremely rare outside major histocompatibility
      complex genes. Our data indicate that the DEFB1 promoter region carries
      functional variants and support previous hypotheses whereby alleles predisposing
      to atopic disorders are widespread in modern societies because they conferred
      resistance to pathogens in ancient settings.

PMID- 18817539
TI  - A synaptic nidogen: developmental regulation and role of nidogen-2 at the
      neuromuscular junction.
AB  - BACKGROUND: The skeletal neuromuscular junction is a useful model for elucidating
      mechanisms that regulate synaptogenesis. Developmentally important intercellular
      interactions at the neuromuscular junction are mediated by the synaptic portion
      of a basal lamina that completely ensheaths each muscle fiber. Basal laminas in
      general are composed of four main types of glycosylated proteins: laminins,
      collagens IV, heparan sulfate proteoglycans and nidogens (entactins). The portion
      of the muscle fiber basal lamina that passes between the motor nerve terminal and
      postsynaptic membrane has been shown to bear distinct isoforms of the first three
      of these. For laminins and collagens IV, the proteins are deposited by the
      muscle; a synaptic proteoglycan, z-agrin, is deposited by the nerve. In each
      case, the synaptic isoform plays key roles in organizing the neuromuscular
      junction. Here, we analyze the fourth family, composed of nidogen-1 and -2.
      RESULTS: In adult muscle, nidogen-1 is present throughout muscle fiber basal
      lamina, while nidogen-2 is concentrated at synapses. Nidogen-2 is initially
      present throughout muscle basal lamina, but is lost from extrasynaptic regions
      during the first three postnatal weeks. Neuromuscular junctions in mutant mice
      lacking nidogen-2 appear normal at birth, but become topologically abnormal as
      they mature. Synaptic laminins, collagens IV and heparan sulfate proteoglycans
      persist in the absence of nidogen-2, suggesting the phenotype is not secondary to
      a general defect in the integrity of synaptic basal lamina. Further genetic
      studies suggest that synaptic localization of each of the four families of
      synaptic basal lamina components is independent of the other three. CONCLUSION:
      All four core components of the basal lamina have synaptically enriched isoforms.
      Together, they form a highly specialized synaptic cleft material. Individually,
      they play distinct roles in the formation, maturation and maintenance of the
      neuromuscular junction.

PMID- 18817540
TI  - Parameter estimation and determinability analysis applied to Drosophila gap gene
      circuits.
AB  - BACKGROUND: Mathematical modeling of real-life processes often requires the
      estimation of unknown parameters. Once the parameters are found by means of
      optimization, it is important to assess the quality of the parameter estimates,
      especially if parameter values are used to draw biological conclusions from the
      model. RESULTS: In this paper we describe how the quality of parameter estimates
      can be analyzed. We apply our methodology to assess parameter determinability for
      gene circuit models of the gap gene network in early Drosophila embryos.
      CONCLUSION: Our analysis shows that none of the parameters of the considered
      model can be determined individually with reasonable accuracy due to correlations
      between parameters. Therefore, the model cannot be used as a tool to infer
      quantitative regulatory weights. On the other hand, our results show that it is
      still possible to draw reliable qualitative conclusions on the regulatory
      topology of the gene network. Moreover, it improves previous analyses of the same
      model by allowing us to identify those interactions for which qualitative
      conclusions are reliable, and those for which they are ambiguous.

PMID- 18817541
TI  - Regulation of expression of two LY-6 family genes by intron retention and
      transcription induced chimerism.
AB  - BACKGROUND: Regulation of the expression of particular genes can rely on
      mechanisms that are different from classical transcriptional and translational
      control. The LY6G5B and LY6G6D genes encode LY-6 domain proteins, whose
      expression seems to be regulated in an original fashion, consisting of an intron
      retention event which generates, through an early premature stop codon, a non
      coding transcript, preventing expression in most cell lines and tissues. RESULTS:
      The MHC LY-6 non-coding transcripts have shown to be stable and very abundant in
      the cell, and not subject to Nonsense Mediated Decay (NMD). This retention event
      appears not to be solely dependent on intron features, because in the case of
      LY6G5B, when the intron is inserted in the artificial context of a luciferase
      expression plasmid, it is fully spliced but strongly stabilises the resulting
      luciferase transcript. In addition, by quantitative PCR we found that the
      retained and spliced forms are differentially expressed in tissues indicating an
      active regulation of the non-coding transcript. EST database analysis revealed
      that these genes have an alternative expression pathway with the formation of
      Transcription Induced Chimeras (TIC). This data was confirmed by RT-PCR,
      revealing the presence of different transcripts that would encode the chimeric
      proteins CSNKbeta-LY6G5B and G6F-LY6G6D, in which the LY-6 domain would join to a
      kinase domain and an Ig-like domain, respectively. CONCLUSION: In conclusion, the
      LY6G5B and LY6G6D intron-retained transcripts are not subjected to NMD and are
      more abundant than the properly spliced forms. In addition, these genes form
      chimeric transcripts with their neighbouring same orientation 5' genes. Of
      interest is the fact that the 5' genes (CSNKbeta or G6F) undergo differential
      splicing only in the context of the chimera (CSNKbeta-LY6G5B or G6F-LY6G6C) and
      not on their own.

PMID- 18817542
TI  - Direct contact of platelets and their released products exert different effects
      on human dendritic cell maturation.
AB  - BACKGROUND: Dendritic cells (DCs) are antigen presenting cells capable of
      inducing innate and adaptive immune responses. According to the stimulus and
      their maturation state, DCs induce immunogenic or tolerogenic responses.
      Platelets (PLTs), which are involved in haemostasis and inflammation, can also
      interact with DCs. In this study, we examined the effect of PLTs on DC maturation
      in vitro. Human monocyte-derived DCs were co-cultured for 2 days with homologous
      PLTs either in the same well or in 0.4 mum-pore size filter-separated
      compartments. RESULTS: Confocal microscopy showed the attachment of PLTs to DC
      membranes. The DC receptor involved in this interactions was found to be CD162.
      In addition, we observed that DCs co-cultured with PLTs in filter-separated
      compartments acquired a mature phenotype (high CD80, CD86, and intermediate CD83
      expression; IL-12(p70) production; efficient stimulation of autologous CD4+ T
      cell proliferation), while DCs co-cultured with PLTs in the same compartment did
      not undergo phenotypic maturation, did not secrete IL-12(p70) or IL-1beta, but
      instead induced moderate Th2-polarized T cell proliferation. CONCLUSION: These
      data indicate that (i) PLTs secrete a soluble DC-activating factor that was
      demonstrated not to be soluble CD40-Ligand (CD154; as could have been expected
      from in vivo and previous in vitro work) but to be nucleotide, and (ii) that cell
      to-cell contact did not induce DC maturation, possibly because nucleotide release
      by PLTs was prevented by direct contact with DCs. This work demonstrates that
      PLTs are active elements of the immune system that might play a role in balancing
      the ability of DCs to polarize T cell responses, therefore making them critical
      factors in transfusion processes.

PMID- 18817543
TI  - Rho kinase inhibitors Y27632 and H1152 augment neurite extension in the presence
      of cultured Schwann cells.
AB  - BACKGROUND: RhoA and Rho kinase inhibitors overcome the inhibition of axonal
      regeneration posed by central nervous system (CNS) substrates. METHODS: To
      investigate if inhibition of the Rho pathway augments the neurite extension that
      naturally occurs in the peripheral nervous system (PNS) following nerve damage,
      dorsal root ganglion neurons and Schwann cell co-cultures were incubated with
      culture medium, C3 fusion toxin, and the Rho kinase (ROCK) inhibitors Y27632 and
      H1152. The longest neurite per neuron were measured and compared. Incubation with
      Y27632 and H1152 resulted in significantly longer neurites than controls when the
      neurons were in contact with Schwann cells. When separated by a porous P.E.T.
      membrane, only the group incubated with H1152 developed significantly longer
      neurites. This work demonstrates that Rho kinase inhibition augments neurite
      elongation in the presence of contact with a PNS-like substrate.

PMID- 18817544
TI  - Assessment of the primary rotational stability of uncemented hip stems using an
      analytical model: comparison with finite element analyses.
AB  - BACKGROUND: Sufficient primary stability is a prerequisite for the clinical
      success of cementless implants. Therefore, it is important to have an estimation
      of the primary stability that can be achieved with new stem designs in a pre
      clinical trial. Fast assessment of the primary stability is also useful in the
      preoperative planning of total hip replacements, and to an even larger extent in
      intraoperatively custom-made prosthesis systems, which result in a wide variety
      of stem geometries. METHODS: An analytical model is proposed to numerically
      predict the relative primary stability of cementless hip stems. This analytical
      approach is based upon the principle of virtual work and a straightforward
      mechanical model. For five custom-made implant designs, the resistance against
      axial rotation was assessed through the analytical model as well as through
      finite element modelling (FEM). RESULTS: The analytical approach can be
      considered as a first attempt to theoretically evaluate the primary stability of
      hip stems without using FEM, which makes it fast and inexpensive compared to
      other methods. A reasonable agreement was found in the stability ranking of the
      stems obtained with both methods. However, due to the simplifying assumptions
      underlying the analytical model it predicts very rigid stability behaviour:
      estimated stem rotation was two to three orders of magnitude smaller, compared
      with the FEM results. CONCLUSION: Based on the results of this study, the
      analytical model might be useful as a comparative tool for the assessment of the
      primary stability of cementless hip stems.

PMID- 18817545
TI  - HIV, visceral leishmaniasis and Parkinsonism combined with diabetes mellitus and
      hyperuricaemia: A case report.
AB  - BACKGROUND: Visceral leishmaniasis is caused by a protozoan parasite, Leishmania
      donovani and transmitted by the bite of female sandflies. India is endemic for
      this disease. On the other hand, India contributes to the largest number of cases
      of HIV as well. CASE PRESENTATION: We hereby report an unusual case presentation
      of Visceral leishmaniasis/HIV co-infection with additional features of
      Parkinsonism and hyperuriciemia in an Indian male patient aged about 50 years.
      CONCLUSION: The increasing incidence of HIV/VL co-infection in India is of utmost
      importance. The diagnostic and management aspects of these cases are very
      difficult to handle particularly in an underdeveloped country like India.

PMID- 18817546
TI  - Building blocks for automated elucidation of metabolites: machine learning
      methods for NMR prediction.
AB  - BACKGROUND: Current efforts in Metabolomics, such as the Human Metabolome
      Project, collect structures of biological metabolites as well as data for their
      characterisation, such as spectra for identification of substances and
      measurements of their concentration. Still, only a fraction of existing
      metabolites and their spectral fingerprints are known. Computer-Assisted
      Structure Elucidation (CASE) of biological metabolites will be an important tool
      to leverage this lack of knowledge. Indispensable for CASE are modules to predict
      spectra for hypothetical structures. This paper evaluates different statistical
      and machine learning methods to perform predictions of proton NMR spectra based
      on data from our open database NMRShiftDB. RESULTS: A mean absolute error of 0.18
      ppm was achieved for the prediction of proton NMR shifts ranging from 0 to 11
      ppm. Random forest, J48 decision tree and support vector machines achieved
      similar overall errors. HOSE codes being a notably simple method achieved a
      comparatively good result of 0.17 ppm mean absolute error. CONCLUSION: NMR
      prediction methods applied in the course of this work delivered precise
      predictions which can serve as a building block for Computer-Assisted Structure
      Elucidation for biological metabolites.

PMID- 18817547
TI  - Persisting atypical and cystic forms of Borrelia burgdorferi and local
      inflammation in Lyme neuroborreliosis.
AB  - BACKGROUND: The long latent stage seen in syphilis, followed by chronic central
      nervous system infection and inflammation, can be explained by the persistence of
      atypical cystic and granular forms of Treponema pallidum. We investigated whether
      a similar situation may occur in Lyme neuroborreliosis. METHOD: Atypical forms of
      Borrelia burgdorferi spirochetes were induced exposing cultures of Borrelia
      burgdorferi (strains B31 and ADB1) to such unfavorable conditions as osmotic and
      heat shock, and exposure to the binding agents Thioflavin S and Congo red. We
      also analyzed whether these forms may be induced in vitro, following infection of
      primary chicken and rat neurons, as well as rat and human astrocytes. We further
      analyzed whether atypical forms similar to those induced in vitro may also occur
      in vivo, in brains of three patients with Lyme neuroborreliosis. We used
      immunohistochemical methods to detect evidence of neuroinflammation in the form
      of reactive microglia and astrocytes. RESULTS: Under these conditions we observed
      atypical cystic, rolled and granular forms of these spirochetes. We characterized
      these abnormal forms by histochemical, immunohistochemical, dark field and atomic
      force microscopy (AFM) methods. The atypical and cystic forms found in the brains
      of three patients with neuropathologically confirmed Lyme neuroborreliosis were
      identical to those induced in vitro. We also observed nuclear fragmentation of
      the infected astrocytes using the TUNEL method. Abundant HLA-DR positive
      microglia and GFAP positive reactive astrocytes were present in the cerebral
      cortex. CONCLUSION: The results indicate that atypical extra- and intracellular
      pleomorphic and cystic forms of Borrelia burgdorferi and local neuroinflammation
      occur in the brain in chronic Lyme neuroborreliosis. The persistence of these
      more resistant spirochete forms, and their intracellular location in neurons and
      glial cells, may explain the long latent stage and persistence of Borrelia
      infection. The results also suggest that Borrelia burgdorferi may induce cellular
      dysfunction and apoptosis. The detection and recognition of atypical, cystic and
      granular forms in infected tissues is essential for the diagnosis and the
      treatment as they can occur in the absence of the typical spiral Borrelia form.

PMID- 18817548
TI  - Geographic risk modeling of childhood cancer relative to county-level crops,
      hazardous air pollutants and population density characteristics in Texas.
AB  - BACKGROUND: Childhood cancer has been linked to a variety of environmental
      factors, including agricultural activities, industrial pollutants and population
      mixing, but etiologic studies have often been inconclusive or inconsistent when
      considering specific cancer types. More specific exposure assessments are needed.
      It would be helpful to optimize future studies to incorporate knowledge of high
      risk locations or geographic risk patterns. The objective of this study was to
      evaluate potential geographic risk patterns in Texas accounting for the
      possibility that multiple cancers may have similar geographic risks patterns.
      METHODS: A spatio-temporal risk modeling approach was used, whereby 19 childhood
      cancer types were modeled as potentially correlated within county-years. The
      standard morbidity ratios were modeled as functions of intensive crop production,
      intensive release of hazardous air pollutants, population density, and rapid
      population growth. RESULTS: There was supportive evidence for elevated risks for
      germ cell tumors and "other" gliomas in areas of intense cropping and for hepatic
      tumors in areas of intense release of hazardous air pollutants. The risk for
      Hodgkin lymphoma appeared to be reduced in areas of rapidly growing population.
      Elevated spatial risks included four cancer histotypes, "other" leukemias,
      Central Nervous System (CNS) embryonal tumors, CNS other gliomas and hepatic
      tumors with greater than 95% likelihood of elevated risks in at least one county.
      CONCLUSION: The Bayesian implementation of the Multivariate Conditional
      Autoregressive model provided a flexible approach to the spatial modeling of
      multiple childhood cancer histotypes. The current study identified geographic
      factors supporting more focused studies of germ cell tumors and "other" gliomas
      in areas of intense cropping, hepatic cancer near Hazardous Air Pollutant (HAP)
      release facilities and specific locations with increased risks for CNS embryonal
      tumors and for "other" leukemias. Further study should be performed to evaluate
      potentially lower risk for Hodgkin lymphoma and malignant bone tumors in counties
      with rapidly growing population.

PMID- 18817549
TI  - Reference population for international comparisons and time trend surveillance of
      preterm delivery proportions in three countries.
AB  - BACKGROUND: International comparison and time trend surveillance of preterm
      delivery rates is complex. New techniques that could facilitate interpretation of
      such rates are needed. METHODS: We studied all live births and stillbirths (>or=
      28 weeks gestation) registered in the medical birth registers in Sweden, Denmark
      and Norway from 1995 through 2004. Gestational age was determined by best
      estimate. A reference population of pregnant women was designed using the
      following criteria: 1) maternal age 20-35, 2) primiparity, 3) spontaneously
      conceived pregnancy, 4) singleton pregnancy and 5) mother born in the respective
      country. National preterm delivery rate, preterm delivery rate in the reference
      population and rate of spontaneous preterm delivery in the reference population
      were calculated for each country. RESULTS: The total national preterm delivery
      rate (< 37 completed gestational weeks), increased in both Denmark (5.3% to 6.1%,
      p < 0.001) and Norway (6.0% to 6.4%, p = 0.006), but remained unchanged in
      Sweden, during 1995-2004. In Denmark, the preterm delivery rate in the reference
      population (5.3% to 6.3%, p < 0.001) and the spontaneous preterm delivery rate in
      the reference population (4.4% to 6.8%, p < 0.001) increased significantly. No
      similar increase was evident in Norway. In Sweden, rates in the reference
      population remained stable. CONCLUSION: Reference populations can facilitate
      overview and thereby explanations for changing preterm delivery rates. The model
      also permits comparisons over time. This model may in its simplicity prove to be
      a valuable supplement to assessments of national preterm delivery rates for
      public health surveillance.

PMID- 18817550
TI  - Ultrastructural pathology of nephropathies with organized deposits: a case
      series.
AB  - Renal organized or structured deposits are much less frequent than those with
      usual type immunocomplex deposits and are encountered in a wide variety of
      primary and systemic disorders. It has been suggested that immunoglobulins (Igs)
      are responsible for organized deposits. We report 5 cases who have been diagnosed
      and treated in our hospital. Patients were aged 52 to 72 years, three of them
      were males and had variable degree of renal function, from normal serum
      creatinine to uraemia. Proteinuria was detected in all patients while monoclonal
      component was present only in the serum of one subject. Ultrastructural analysis
      of renal specimens revealed organized deposits. Diagnoses that were made are the
      following: membranoproliferative glomerulonephritis with finger print,
      immunotactoid glomerulopathy, membranoproliferative glomerulonephritis with
      arched deposits, primary amyloidosis and light chain deposition disease. In
      systemic disorders ultrastructural pathology could be particularly valuable for
      correct deposits classification, precise localization and pattern of deposition
      of Igs.

PMID- 18817551
TI  - Using gene expression databases for classical trait QTL candidate gene discovery
      in the BXD recombinant inbred genetic reference population: mouse forebrain
      weight.
AB  - BACKGROUND: Successful strategies for QTL gene identification benefit from
      combined experimental and bioinformatic approaches. Unique design aspects of the
      BXD recombinant inbred line mapping panel allow use of archived gene microarray
      expression data to filter likely from unlikely candidates. This prompted us to
      propose a simple five-filter protocol for candidate nomination. To filter more
      likely from less likely candidates, we required candidate genes near to the QTL
      to have mRNA abundance that correlated with the phenotype among the BXD lines as
      well as differed between the parental lines C57BL/6J and DBA/2J. We also required
      verification of mRNA abundance by an independent method, and finally we required
      either differences in protein levels or confirmed DNA sequence differences.
      RESULTS: QTL mapping of mouse forebrain weight in 34 BXD RI lines found
      significant association on chromosomes 1 and 11, with each C57BL/6J allele
      increasing weight by more than half a standard deviation. The intersection of
      gene lists that were within +/- 10 Mb of the strongest associated location, that
      had forebrain mRNA abundance correlated with forebrain weight among the BXD, and
      that had forebrain mRNA abundance differing between C57BL/6J and DBA/2J, produced
      two candidates, Tnni1 (troponin 1) and Asb3 (ankyrin repeat and SOCS box
      containing protein 3). Quantitative RT-PCR confirmed the direction of an
      increased expression in C57BL/6J genotype over the DBA/2J genotype for both
      genes, a difference that translated to a 2-fold difference in Asb3 protein.
      Although Tnni1 protein differences could not be confirmed, a 273 bp indel
      polymorphism was discovered 1 Kb upstream of the transcription start site.
      CONCLUSION: Delivery of well supported candidate genes following a single
      quantitative trait locus mapping experiment is difficult. However, by combining
      available gene expression data with QTL mapping, we illustrated a five-filter
      protocol that nominated Asb3 and Tnni1 as candidates affecting increased mouse
      forebrain weight. We recommend our approach when (1) investigators are working
      with phenotypic differences between C57BL/6J and DBA/2J, and (2) gene expression
      data are available on http://www.genenetwork.org that relate to the phenotype of
      interest. Under these circumstances, measurement of the phenotype in the BXD
      lines will likely also deliver excellent candidate genes.

PMID- 18817552
TI  - Developing and validating predictive decision tree models from mining chemical
      structural fingerprints and high-throughput screening data in PubChem.
AB  - BACKGROUND: Recent advances in high-throughput screening (HTS) techniques and
      readily available compound libraries generated using combinatorial chemistry or
      derived from natural products enable the testing of millions of compounds in a
      matter of days. Due to the amount of information produced by HTS assays, it is a
      very challenging task to mine the HTS data for potential interest in drug
      development research. Computational approaches for the analysis of HTS results
      face great challenges due to the large quantity of information and significant
      amounts of erroneous data produced. RESULTS: In this study, Decision Trees (DT)
      based models were developed to discriminate compound bioactivities by using their
      chemical structure fingerprints provided in the PubChem system
      http://pubchem.ncbi.nlm.nih.gov. The DT models were examined for filtering
      biological activity data contained in four assays deposited in the PubChem
      Bioassay Database including assays tested for 5HT1a agonists, antagonists, and
      HIV-1 RT-RNase H inhibitors. The 10-fold Cross Validation (CV) sensitivity,
      specificity and Matthews Correlation Coefficient (MCC) for the models are 57.2
      approximately 80.5%, 97.3 approximately 99.0%, 0.4 approximately 0.5
      respectively. A further evaluation was also performed for DT models built for two
      independent bioassays, where inhibitors for the same HIV RNase target were
      screened using different compound libraries, this experiment yields enrichment
      factor of 4.4 and 9.7. CONCLUSION: Our results suggest that the designed DT
      models can be used as a virtual screening technique as well as a complement to
      traditional approaches for hits selection.

PMID- 18817553
TI  - Improved survival of thalassaemia major in the UK and relation to T2*
      cardiovascular magnetic resonance.
AB  - BACKGROUND: The UK Thalassaemia Register records births, deaths and selected
      clinical data of patients with thalassaemia who are resident in the UK. A study
      of survival and causes of death was undertaken which aimed to include the
      possible impact of T2* cardiovascular magnetic resonance (CMR). METHODS: The
      Register was updated to the end of 2003, copies of death certificates were
      obtained, and causes of death in beta thalassaemia major were extracted. In
      addition, patients who had T2* CMR assessment of cardiac iron load and/or
      received the oral iron chelator deferiprone were identified from clinical
      records. RESULTS: The main causes of death were anaemia (before 1980),
      infections, complications of bone marrow transplantation and cardiac disease due
      to iron overload. From 1980 to 1999 there were 12.7 deaths from all causes per
      1,000 patient years. Forty per cent of patients born before 1980 had T2*
      cardiovascular magnetic resonance between 2000 and 2003, and 36% of these
      patients were prescribed deferiprone before end of 2003. In 2000-2003, the death
      rate from all causes fell significantly to 4.3 per 1,000 patient years (-62%, p <
      0.05). This was mainly driven by the reduction in the rate of deaths from iron
      overload which fell from 7.9 to 2.3 deaths per 1,000 patient years (-71%, p <
      0.05). CONCLUSION: Since 1999, there has been a marked improvement in survival in
      thalassaemia major in the UK, which has been mainly driven by a reduction in
      deaths due to cardiac iron overload. The most likely causes for this include the
      introduction of T2* CMR to identify myocardial siderosis and appropriate
      intensification of iron chelation treatment, alongside other improvements in
      clinical care.

PMID- 18817554
TI  - Cross-modal deactivations during modality-specific selective attention.
AB  - BACKGROUND: Processing stimuli in one sensory modality is known to result in
      suppression of other sensory-specific cortices. Additionally, behavioral
      experiments suggest that the primary consequence of paying attention to a
      specific sensory modality is poorer task performance in the unattended sensory
      modality. This study was designed to determine how focusing attention on the
      auditory or visual modality impacts neural activity in cortical regions
      responsible for processing stimuli in the unattended modality. METHODS:
      Functional MRI data were collected in 15 participants who completed a cued
      detection paradigm. This task allowed us to assess the effects of modality
      specific attention both during the presence and the absence of targets in the
      attended modality. RESULTS: The results of this experiment demonstrate that
      attention to a single sensory modality can result in decreased activity in
      cortical regions that process information from an unattended sensory modality
      (cross-modal deactivations). The effects of attention are likely additive with
      stimulus-driven effects with the largest deactivations being observed during
      modality-specific selective attention, in the presence of a stimulus in that
      modality. CONCLUSION: Modality-specific selective attention results in behavioral
      decrements in unattended sensory modalities. The imaging results presented here
      provide a neural signature (cross-modal deactivation) for modality-specific
      selective attention.

PMID- 18817555
TI  - Abbreviation definition identification based on automatic precision estimates.
AB  - BACKGROUND: The rapid growth of biomedical literature presents challenges for
      automatic text processing, and one of the challenges is abbreviation
      identification. The presence of unrecognized abbreviations in text hinders
      indexing algorithms and adversely affects information retrieval and extraction.
      Automatic abbreviation definition identification can help resolve these issues.
      However, abbreviations and their definitions identified by an automatic process
      are of uncertain validity. Due to the size of databases such as MEDLINE only a
      small fraction of abbreviation-definition pairs can be examined manually. An
      automatic way to estimate the accuracy of abbreviation-definition pairs extracted
      from text is needed. In this paper we propose an abbreviation definition
      identification algorithm that employs a variety of strategies to identify the
      most probable abbreviation definition. In addition our algorithm produces an
      accuracy estimate, pseudo-precision, for each strategy without using a human
      judged gold standard. The pseudo-precisions determine the order in which the
      algorithm applies the strategies in seeking to identify the definition of an
      abbreviation. RESULTS: On the Medstract corpus our algorithm produced 97%
      precision and 85% recall which is higher than previously reported results. We
      also annotated 1250 randomly selected MEDLINE records as a gold standard. On this
      set we achieved 96.5% precision and 83.2% recall. This compares favourably with
      the well known Schwartz and Hearst algorithm. CONCLUSION: We developed an
      algorithm for abbreviation identification that uses a variety of strategies to
      identify the most probable definition for an abbreviation and also produces an
      estimated accuracy of the result. This process is purely automatic.

PMID- 18817556
TI  - The prognostic value of nestin expression in newly diagnosed glioblastoma: report
      from the Radiation Therapy Oncology Group.
AB  - BACKGROUND: Nestin is an intermediate filament protein that has been implicated
      in early stages of neuronal lineage commitment. Based on the heterogeneous
      expression of nestin in GBM and its potential to serve as a marker for a
      dedifferentiated, and perhaps more aggressive phenotype, the Radiation Therapy
      Oncology Group (RTOG) sought to determine the prognostic value of nestin
      expression in newly diagnosed GBM patients treated on prior prospective RTOG
      clinical trials. METHODS: Tissue microarrays were prepared from 156 patients
      enrolled in these trials. These specimens were stained using a mouse monoclonal
      antibody specific for nestin and expression was measured by computerized
      quantitative image analysis using the Ariol SL-50 system. The parameters measured
      included both staining intensity and the relative area of expression within a
      specimen. This resulted into 3 categories: low, intermediate, and high nestin
      expression, which was then correlated with clinical outcome. RESULTS: A total of
      153 of the 156 samples were evaluable for this study. There were no statistically
      significant differences between pretreatment patient characteristics and nestin
      expression. There was no statistically significant difference in either overall
      survival or progression-free survival (PFS) demonstrated, although a trend in
      decreased PFS was observed with high nestin expression (p = 0.06). CONCLUSION:
      Although the correlation of nestin expression and histologic grade in glioma is
      of considerable interest, the presented data does not support its prognostic
      value in newly diagnosed GBM. Further studies evaluating nestin expression may be
      more informative when studied in lower grade glioma, in the context of markers
      more specific to tumor stem cells, and using more recent specimens from patients
      treated with temozolomide in conjunction with radiation.

PMID- 18817557
TI  - Detection and quantification of angiogenesis in experimental valve disease with
      integrin-targeted nanoparticles and 19-fluorine MRI/MRS.
AB  - BACKGROUND: Angiogenesis is a critical early feature of atherosclerotic plaque
      development and may also feature prominently in the pathogenesis of aortic valve
      stenosis. It has been shown that MRI can detect and quantify specific molecules
      of interest expressed in cardiovascular disease and cancer by measuring the
      unique fluorine signature of appropriately targeted perfluorocarbon (PFC)
      nanoparticles. In this study, we demonstrated specific binding of alphanubeta3
      integrin targeted nanoparticles to neovasculature in a rabbit model of aortic
      valve disease. We also showed that fluorine MRI could be used to detect and
      quantify the development of neovasculature in the excised aortic valve leaflets.
      METHODS: New Zealand White rabbits consumed a cholesterol diet for ~180 days and
      developed aortic valve thickening, inflammation, and angiogenesis mimicking early
      human aortic valve disease. Rabbits (n = 7) were treated with alphanubeta3
      integrin targeted PFC nanoparticles or control untargeted PFC nanoparticles (n =
      6). Competitive inhibition in vivo of nanoparticle binding (n = 4) was tested by
      pretreatment with targeted nonfluorinated nanoparticles followed 2 hours later by
      targeted PFC nanoparticles. 2 hours after treatment, aortic valves were excised
      and 19F MRS was performed at 11.7T. Integrated 19F spectral peaks were compared
      using a one-way ANOVA and Hsu's MCB (multiple comparisons with the best) post hoc
      t test. In 3 additional rabbits treated with alphanubeta3 integrin targeted PFC
      nanoparticles, 19F spectroscopy was performed on a 3.0T clinical scanner. The
      presence of angiogenesis was confirmed by immunohistochemistry. RESULTS: Valves
      of rabbits treated with targeted PFC nanoparticles had 220% more fluorine signal
      than valves of rabbits treated with untargeted PFC nanoparticles (p < 0.001).
      Pretreatment of rabbits with targeted oil-based nonsignaling nanoparticles
      reduced the fluorine signal by 42% due to competitive inhibition, to a level not
      significantly different from control animals. Nanoparticles were successfully
      detected in all samples scanned at 3.0T. PECAM endothelial staining and
      alphanubeta3 integrin staining revealed the presence of neovasculature within the
      valve leaflets. CONCLUSION: Integrin-targeted PFC nanoparticles specifically
      detect early angiogenesis in sclerotic aortic valves of cholesterol fed rabbits.
      These techniques may be useful for assessing atherosclerotic components of
      preclinical aortic valve disease in patients and could assist in defining
      efficacy of medical therapies.

PMID- 18817558
TI  - Brachyspira pilosicoli bloodstream infections: case report and review of the
      literature.
AB  - Brachyspira pilosicoli is the etiologic agent of human and animal intestinal
      spirochetosis and is rarely implicated as a cause of bacteremia. Here, we
      describe the case of a B. pilosicoli spirochetemia in a 53-year-old male patient
      suffering from cardiogenic shock. This fastidious bacterium was isolated from
      blood, likely after translocation from the intestinal tract. Blood cultures were
      positive after 5 days of incubation (one day after the patient's death),
      highlighting the problem of the recovery of such type of fastidious bacterium.
      Identification was achieved by molecular methods (16S rRNA sequencing). A review
      of the English literature found only 8 cases of bacteremia caused by B.
      pilosicoli, mostly in immunocompromised or critically ill patients. Finally,
      difficulties in rapid and accurate diagnosis of B. pilosicoli bloodstream
      infections, in vitro antimicrobial susceptibility of human clinical isolates, and
      therapeutic options are discussed.

PMID- 18817559
TI  - Standardised proformas improve patient handover: Audit of trauma handover
      practice.
AB  - BACKGROUND: The implementation of the European Working Time Directive has meant
      the introduction of shift patterns of working for junior doctors. Patient
      handover between shifts has become a necessary part of practice in order to
      reduce the risk of medical errors. Data handed over between shifts are used to
      prioritise clinical jobs outstanding, and to create theatre lists. We present a
      closed-loop audit of handover practice to assess whether standardised proformas
      improve clinical data transfer between shifts during handover in our Orthopaedic
      Unit. METHODS: We collected data handed over between shifts for a period of one
      week at our department. The data were in the form of hand written data on plain
      paper used to assist verbal handover. Data were analysed and a standardised
      handover sheet was trialled. After feedback from juniors the sheet was revised
      and implemented. A re-audit, of handover data, was then undertaken using the
      revised standardised proforma during a period of 1 week. RESULTS: Forty-eight
      patients were handed over in week 1 while 55 patients were handed over during re
      audit. The standardised proformas encouraged use of pre-printed patient labels
      which contained legible patient identifiers, use of labels increased from 72.9%
      to 93.4%. Handover of outstanding jobs increased from 31.25% to 100%. Overall
      data handed over increased from 72.6% to 93.2%. Handover of relevant blood
      results showed little improvement from 18.8% to 20.7% CONCLUSION: This audit
      highlights the issue of data transfer between shifts. Standardised proformas
      encourage filling of relevant fields and increases the data transferred between
      shifts thereby reducing the potential for clinical error cause by shift patterns.

PMID- 18817561
TI  - Extrapulmonary small cell carcinoma: involvement of the brain without evidence of
      extracranial malignancy by serial PET/CT scans.
AB  - BACKGROUND: Extrapulmonary small cell carcinoma (EPSCC) involving the brain is a
      rare manifestation of an uncommon tumor type. CASE PRESENTATION: We report a 59
      year-old Caucasian female diagnosed with an EPSCC involving the left parietal
      lobe without detectable extracranial primary tumor followed by serial positron
      emission tomography/computed tomography (PET/CT) imaging. Histopathological
      examination at both initial presentation and recurrence revealed small cell
      carcinoma. Serial PET/CT scans of the entire body failed to reveal any
      extracranial [18F]2-fluoro-2-deoxy-D-glucose (FDG) avid lesions at either
      diagnosis or follow-up. CONCLUSION: Chemotherapy may show a transient response in
      the treatment of EPSCC. Further studies are needed to help identify optimal
      treatment strategies. Combination PET/CT technology may be a useful tool to
      monitor EPSCC and assess for an occult primary malignancy.

PMID- 18817562
TI  - Effect of arginase II on L-arginine depletion and cell growth in murine cell
      lines of renal cell carcinoma.
AB  - BACKGROUND: L-arginine is the common substrate for the two isoforms of arginase.
      Arginase I, highly expressed in the liver and arginase II mainly expressed in the
      kidney. Arginase I-producing myeloid derived suppressor cells have been shown to
      inhibit T-cell function by the depletion of L-arginine. On the other hand,
      arginase II has been detected in patients with cancer and is thought to
      metabolize L-arginine to L-ornithine needed to sustain rapid tumor growth;
      however its role in L-arginine depletion is unclear. Thus, in tumor biology, L
      arginine metabolism may play a dual role in tumor growth and in the induction of
      T cell dysfunction. Therefore, we studied in murine renal cell carcinoma (RCC)
      cell lines, the effect of arginase II on tumor cell proliferation and L-arginine
      depletion. The effect of arginase inhibitors on cell proliferation was also
      tested. METHODS: Three murine renal cell carcinoma (mRCC) cell lines were tested
      for the presence of arginase. nor-NOHA, an arginase inhibitor was used to
      substantiate the effect of arginase on cell growth and L-arginine depletion.
      Amino acid levels were tested by HPLC. RESULTS: Our results show that mRCC cell
      lines express only arginase II and were able to deplete L-arginine from the
      medium. Cell growth was independent of the amount of arginase activity expressed
      by the cells. nor-NOHA significantly (P = 0.01) reduced arginase II activity and
      suppressed cell growth in cells exhibiting high arginase activity.The depletion
      of L-arginine by mRCC induced the decrease expression of CD3zeta a key element
      for T-cell function. CONCLUSION: The results of this study show for the first
      time that arginase II produced by RCC cell lines depletes L-arginine resulting in
      decreased expression of CD3zeta. These results indicate that RCC cell lines
      expressing arginase II can modulate the L-arginine metabolic pathway to regulate
      both cell growth and T-cell function. Blocking arginase may lead to a decrease in
      RCC cell growth and aid in restoring immune function by increasing L-arginine
      availability for T-cell use. Understanding the interplay between arginase II and
      its interaction with the immune system may provide future therapeutic benefits to
      treat patients with RCC.

PMID- 18817563
TI  - An ontology for Xenopus anatomy and development.
AB  - BACKGROUND: The frogs Xenopus laevis and Xenopus (Silurana) tropicalis are model
      systems that have produced a wealth of genetic, genomic, and developmental
      information. Xenbase is a model organism database that provides centralized
      access to this information, including gene function data from high-throughput
      screens and the scientific literature. A controlled, structured vocabulary for
      Xenopus anatomy and development is essential for organizing these data. RESULTS:
      We have constructed a Xenopus anatomical ontology that represents the lineage of
      tissues and the timing of their development. We have classified many anatomical
      features in a common framework that has been adopted by several model organism
      database communities. The ontology is available for download at the Open
      Biomedical Ontologies Foundry http://obofoundry.org. CONCLUSION: The Xenopus
      Anatomical Ontology will be used to annotate Xenopus gene expression patterns and
      mutant and morphant phenotypes. Its robust developmental map will enable powerful
      database searches and data analyses. We encourage community recommendations for
      updates and improvements to the ontology.

PMID- 18817564
TI  - Dynamics of multiple insecticide resistance in the malaria vector Anopheles
      gambiae in a rice growing area in South-Western Burkina Faso.
AB  - BACKGROUND: Insecticide resistance of the main malaria vector, Anopheles gambiae,
      has been reported in south-western Burkina Faso, West Africa. Cross-resistance to
      DDT and pyrethroids was conferred by alterations at site of action in the sodium
      channel, the Leu-Phe kdr mutation; resistance to organophosphates and carbamates
      resulted from a single point mutation in the oxyanion hole of the
      acetylcholinesterase enzyme designed as ace-1R. METHODS: An entomological survey
      was carried out during the rainy season of 2005 at Vallee du Kou, a rice growing
      area in south-western Burkina Faso. At the Vallee du Kou, both insecticide
      resistance mechanisms have been previously described in the M and S molecular
      forms of An. gambiae. This survey aimed i) to update the temporal dynamics and
      the circumsporozoite infection rate of the two molecular forms M and S of An.
      gambiae ii) to update the frequency of the Leu-Phe kdr mutation within these
      forms and finally iii) to investigate the occurrence of the ace-1R mutation.
      Mosquitoes collected by indoor residual collection and by human landing catches
      were counted and morphologically identified. Species and molecular forms of An.
      gambiae, ace-1R and Leu-Phe kdr mutations were determined using PCR techniques.
      The presence of the circumsporozoite protein of Plasmodium falciparum was
      determined using ELISA. RESULTS: Anopheles gambiae populations were dominated by
      the M form. However the S form occurred in relative important proportion towards
      the end of the rainy season with a maximum peak in October at 51%. Sporozoite
      rates were similar in both forms. The frequency of the Leu-Phe kdr mutation in
      the S form reached a fixation level while it is still spreading in the M form.
      Furthermore, the ace-1R mutation prevailed predominately in the S form and has
      just started spreading in the M form. The two mutations occurred concomitantly
      both in M and S populations. CONCLUSION: These results showed that the Vallee du
      Kou, a rice growing area formerly occupied mainly by M susceptible populations,
      is progressively colonized by S resistant populations living in sympatry with the
      former. As a result, the distribution pattern of insecticide resistance mutations
      shows the occurrence of both resistance mechanisms concomitantly in the same
      populations. The impact of multiple resistance mechanisms in M and S populations
      of An. gambiae on vector control measures against malaria transmission, such as
      insecticide-treated nets (ITNs) and indoor residual spraying (IRS), in this area
      is discussed.

PMID- 18817565
TI  - Relative risk of diabetes, dyslipidaemia, hypertension and the metabolic syndrome
      in people with severe mental illnesses: systematic review and metaanalysis.
AB  - BACKGROUND: Severe mental illnesses (SMI) may be independently associated with
      cardiovascular risk factors and the metabolic syndrome. We aimed to
      systematically assess studies that compared diabetes, dyslipidaemia, hypertension
      and metabolic syndrome in people with and without SMI. METHODS: We systematically
      searched MEDLINE, EMBASE, CINAHL & PsycINFO. We hand searched reference lists of
      key articles. We employed three search main themes: SMI, cardiovascular disease,
      and each cardiovascular risk factor. We selected cross-sectional, case control,
      cohort or intervention studies comparing one or more risk factor in both SMI and
      a reference group. We excluded studies without any reference group. We extracted
      data on: study design, cardiovascular risk factor(s) and their measurement,
      diagnosis of SMI, study setting, sampling method, nature of comparison group and
      data on key risk factors. RESULTS: Of 14592 citations, 134 papers met criteria
      and 36 were finally included. 26 reported on diabetes, 12 hypertension, 11
      dyslipidaemia, and 4 metabolic syndrome. Most studies were cross sectional, small
      and several lacked comparison data suitable for extraction. Meta-analysis was
      possible for diabetes, cholesterol and hypertension; revealing a pooled risk
      ratio of 1.70 (1.21 to 2.37) for diabetes and 1.11 (0.91 to 1.35) of
      hypertension. Restricting SMI to schizophreniform illnesses yielded a pooled risk
      ratio for diabetes of 1.87 (1.68 to 2.09). Total cholesterol was not higher in
      people with SMI (Standardized Mean Difference -0.10 (-0.55 to 0.36)) and there
      were inconsistent data on HDL, LDL and triglycerides with some, but not all,
      reporting lower levels of HDL cholesterol and raised triglyceride levels.
      Metabolic syndrome appeared more common in SMI. CONCLUSION: Diabetes (but not
      hypertension) is more common in SMI. Data on other risk factors were limited by
      poor quality or inconsistent research findings, but a small number of studies
      show greater prevalence of the metabolic syndrome in SMI.

PMID- 18817566
TI  - The BHU bicentric bipolar prosthesis in fracture neck femur in active elderly.
AB  - BACKGROUND: 55 BHU bicentric bipolar hemiarthroplasties were reviewed after a
      mean follow up of 4 years (range 1-5 years). Patients with displaced subcapital
      fractures were selected for operation on the basis of good mobility before the
      fracture. Object of the study was to see the efficacy of BHU bipolar prostheses
      and functional outcome. RESULTS: There were no incidences of dislocation.
      Modified Harris hip scoring system scoring system was used which included sitting
      crosslegged and squatting in view of the sociocultural needs of the patients of
      Indian subcontinent. Modified Harris hip scoring system 89% had a good or
      excellent result and 94% had no or only occasional pain. Majority of the patients
      returned to their prefracture activity. CONCLUSION: Thus at follow up of 4 year
      the BHU bicentric bipolar prosthesis has been shown to be a good option for
      intracapsular fractures of neck femur with encouraging results.

PMID- 18817568
TI  - "Enhanced" interrogation of detainees: do psychologists and psychiatrists
      participate?
AB  - After revelations of participation by psychiatrists and psychologists in
      interrogation of prisoners at Guantanamo Bay and Central Intelligence Agency
      secret detention centers, the American Psychiatric Association and the American
      Psychological Association adopted Position Statements absolutely prohibiting
      their members from participating in torture under any and all circumstances, and,
      to a limited degree, forbidding involvement in interrogations. Some
      interrogations utilize very aggressive techniques determined to be torture by
      many nations and organizations throughout the world. This paper explains why
      psychiatrists and psychologists involved in coercive interrogations violate the
      Geneva Conventions and the laws of the United States. Whether done with ignorance
      of professional ethical obligations or not, these psychiatrists and psychologists
      have crossed an ethical barrier that may best be averted from re-occurring by
      teaching medical students and residents in all medical specialties about the
      ethics principles stemming from the 1946-1947 Nuremberg trials and the Geneva
      Conventions, together with the Ethics Codes of the World Medical Association and
      the American Medical Association; and, with regard to psychiatric residents and
      psychological trainees, by the teaching about The Principles of Medical Ethics
      With Annotations Especially Applicable to Psychiatry and the Ethical Principles
      of Psychologists and Code of Conduct, respectively. In this way, all physicians
      and psychologists will clearly understand that they have an absolute moral
      obligation to "First, do no harm" to the human beings they professionally
      encounter.

PMID- 18817569
TI  - A stochastic version of the Price equation reveals the interplay of deterministic
      and stochastic processes in evolution.
AB  - BACKGROUND: Evolution involves both deterministic and random processes, both of
      which are known to contribute to directional evolutionary change. A number of
      studies have shown that when fitness is treated as a random variable, meaning
      that each individual has a distribution of possible fitness values, then both the
      mean and variance of individual fitness distributions contribute to directional
      evolution. Unfortunately the most general mathematical description of evolution
      that we have, the Price equation, is derived under the assumption that both
      fitness and offspring phenotype are fixed values that are known exactly. The
      Price equation is thus poorly equipped to study an important class of
      evolutionary processes. RESULTS: I present a general equation for directional
      evolutionary change that incorporates both deterministic and stochastic processes
      and applies to any evolving system. This is essentially a stochastic version of
      the Price equation, but it is derived independently and contains terms with no
      analog in Price's formulation. This equation shows that the effects of selection
      are actually amplified by random variation in fitness. It also generalizes the
      known tendency of populations to be pulled towards phenotypes with minimum
      variance in fitness, and shows that this is matched by a tendency to be pulled
      towards phenotypes with maximum positive asymmetry in fitness. This equation also
      contains a term, having no analog in the Price equation, that captures cases in
      which the fitness of parents has a direct effect on the phenotype of their
      offspring. CONCLUSION: Directional evolution is influenced by the entire
      distribution of individual fitness, not just the mean and variance. Though all
      moments of individuals' fitness distributions contribute to evolutionary change,
      the ways that they do so follow some general rules. These rules are invisible to
      the Price equation because it describes evolution retrospectively. An equally
      general prospective evolution equation compliments the Price equation and shows
      that the influence of stochastic processes on directional evolution is more
      diverse than has generally been recognized.

PMID- 18817570
TI  - Co-up-regulation of three P450 genes in response to permethrin exposure in
      permethrin resistant house flies, Musca domestica.
AB  - BACKGROUND: Insects may use various biochemical pathways to enable them to
      tolerate the lethal action of insecticides. For example, increased cytochrome
      P450 detoxification is known to play an important role in many insect species.
      Both constitutively increased expression (overexpression) and induction of P450s
      are thought to be responsible for increased levels of detoxification of
      insecticides. However, unlike constitutively overexpressed P450 genes, whose
      expression association with insecticide resistance has been extensively studied,
      the induction of P450s is less well characterized in insecticide resistance. The
      current study focuses on the characterization of individual P450 genes that are
      induced in response to permethrin treatment in permethrin resistant house flies.
      RESULTS: The expression of 3 P450 genes, CYP4D4v2, CYP4G2, and CYP6A38, was co-up
      regulated by permethrin treatment in permethrin resistant ALHF house flies in a
      time and dose-dependent manner. Comparison of the deduced protein sequences of
      these three P450s from resistant ALHF and susceptible aabys and CS house flies
      revealed identical protein sequences. Genetic linkage analysis located CYP4D4v2
      and CYP6A38 on autosome 5, corresponding to the linkage of P450-mediated
      resistance in ALHF, whereas CYP4G2 was located on autosome 3, where the major
      insecticide resistance factor(s) for ALHF had been mapped but no P450 genes
      reported prior to this study. CONCLUSION: Our study provides the first direct
      evidence that multiple P450 genes are co-up-regulated in permethrin resistant
      house flies through the induction mechanism, which increases overall expression
      levels of P450 genes in resistant house flies. Taken together with the
      significant induction of CYP4D4v2, CYP4G2, and CYP6A38 expression by permethrin
      only in permethrin resistant house flies and the correlation of the linkage of
      the genes with resistance and/or P450-mediated resistance in resistant ALHF house
      flies, this study sheds new light on the functional importance of P450 genes in
      response to insecticide treatment, detoxification of insecticides, the adaptation
      of insects to their environment, and the evolution of insecticide resistance.

PMID- 18817567
TI  - Expressed sequence tags (ESTs) from immune tissues of turbot (Scophthalmus
      maximus) challenged with pathogens.
AB  - BACKGROUND: The turbot (Scophthalmus maximus; Scophthalmidae; Pleuronectiformes)
      is a flatfish species of great relevance for marine aquaculture in Europe. In
      contrast to other cultured flatfish, very few genomic resources are available in
      this species. Aeromonas salmonicida and Philasterides dicentrarchi are two
      pathogens that affect turbot culture causing serious economic losses to the
      turbot industry. Little is known about the molecular mechanisms for disease
      resistance and host-pathogen interactions in this species. In this work,
      thousands of ESTs for functional genomic studies and potential markers linked to
      ESTs for mapping (microsatellites and single nucleotide polymorphisms (SNPs)) are
      provided. This information enabled us to obtain a preliminary view of regulated
      genes in response to these pathogens and it constitutes the basis for subsequent
      and more accurate microarray analysis. RESULTS: A total of 12584 cDNAs partially
      sequenced from three different cDNA libraries of turbot (Scophthalmus maximus)
      infected with Aeromonas salmonicida, Philasterides dicentrarchi and from healthy
      fish were analyzed. Three immune-relevant tissues (liver, spleen and head kidney)
      were sampled at several time points in the infection process for library
      construction. The sequences were processed into 9256 high-quality sequences,
      which constituted the source for the turbot EST database. Clustering and assembly
      of these sequences, revealed 3482 different putative transcripts, 1073 contigs
      and 2409 singletons. BLAST searches with public databases detected significant
      similarity (e-value < or = 1e-5) in 1766 (50.7%) sequences and 816 of them
      (23.4%) could be functionally annotated. Two hundred three of these genes
      (24.9%), encoding for defence/immune-related proteins, were mostly identified for
      the first time in turbot. Some ESTs showed significant differences in the number
      of transcripts when comparing the three libraries, suggesting regulation in
      response to these pathogens. A total of 191 microsatellites, with 104 having
      sufficient flanking sequences for primer design, and 1158 putative SNPs were
      identified from these EST resources in turbot. CONCLUSION: A collection of 9256
      high-quality ESTs was generated representing 3482 unique turbot sequences. A
      large proportion of defence/immune-related genes were identified, many of them
      regulated in response to specific pathogens. Putative microsatellites and SNPs
      were identified. These genome resources constitute the basis to develop a
      microarray for functional genomics studies and marker validation for genetic
      linkage and QTL analysis in turbot.

PMID- 18817571
TI  - A prospective study of the psychobehavioral factors responsible for a change from
      non-patient irritable bowel syndrome to IBS patient status.
AB  - BACKGROUND: To investigate non-patient irritable bowel syndrome (IBS) change to
      IBS and to determine factors predictive of the onset of IBS, individual
      biological factors, psychological factors, behavioral factors, and environmental
      factors were examined. METHODS: The subjects were 105 non-patient IBS (male = 59,
      female = 46, average age:21.49 +/- 2.37), including 68 of the diarrhea
      predominant type and 37 of the constipation-predominant type selected from 1,409
      university and technical college students by use of a questionnaire based on the
      Rome II diagnostic criteria. The subjects were followed for three years, and
      various characteristics and IBS symptoms were serially observed (12 times). The
      IBS incidence rate was calculated. RESULTS: During the three years, 37 non
      patient IBS (35.24%) changed to IBS: 28 diarrhea-predominant type and 9
      constipation-predominant type. All IBS symptoms disappeared in 26 non-patient IBS
      subjects (24.76%). According to quantification method II (discriminant analysis),
      seven factors (stressor, two kinds of stress coping styles, cognitive appraisal,
      eating habits, sleeping time, and psychologically abuse) were adopted as a
      predictive model for IBS incidence and were confirmed as predictive of IBS.
      CONCLUSION: The results of this research show that non-patient IBS is a
      changeable state that can change into IBS or persons without symptoms. Most of
      the non-patient IBS subjects who became asymptomatic had had symptoms for six
      months or less. Furthermore, the longer a non-patient IBS subject had symptoms,
      the higher the risk of a change to IBS became. The findings suggest the
      usefulness of identifying and approaching non-patient IBS as early as possible to
      prevent the onset of IBS. It must be noted that the persons surveyed in the
      present study had only the diarrhea-predominant and constipation-predominant
      types. Therefore, the findings of the present study are limited only these two
      types. Further study including the mixed type is needed.

PMID- 18817572
TI  - Centronuclear (myotubular) myopathy.
AB  - Centronuclear myopathy (CNM) is an inherited neuromuscular disorder characterised
      by clinical features of a congenital myopathy and centrally placed nuclei on
      muscle biopsy.The incidence of X-linked myotubular myopathy is estimated at
      2/100000 male births but epidemiological data for other forms are not currently
      available.The clinical picture is highly variable. The X-linked form usually
      gives rise to a severe phenotype in males presenting at birth with marked
      weakness and hypotonia, external ophthalmoplegia and respiratory failure. Signs
      of antenatal onset comprise reduced foetal movements, polyhydramnios and thinning
      of the ribs on chest radiographs; birth asphyxia may be the present. Affected
      infants are often macrosomic, with length above the 90th centile and large head
      circumference. Testes are frequently undescended. Both autosomal-recessive (AR)
      and autosomal-dominant (AD) forms differ from the X-linked form regarding age at
      onset, severity, clinical characteristics and prognosis. In general, AD forms
      have a later onset and milder course than the X-linked form, and the AR form is
      intermediate in both respects.Mutations in the myotubularin (MTM1) gene on
      chromosome Xq28 have been identified in the majority of patients with the X
      linked recessive form, whilst AD and AR forms have been associated with mutations
      in the dynamin 2 (DNM2) gene on chromosome 19p13.2 and the amphiphysin 2 (BIN1)
      gene on chromosome 2q14, respectively. Single cases with features of CNM have
      been associated with mutations in the skeletal muscle ryanodine receptor (RYR1)
      and the hJUMPY (MTMR14) genes.Diagnosis is based on typical histopathological
      findings on muscle biopsy in combination with suggestive clinical features;
      muscle magnetic resonance imaging may complement clinical assessment and inform
      genetic testing in cases with equivocal features. Genetic counselling should be
      offered to all patients and families in whom a diagnosis of CNM has been made.The
      main differential diagnoses include congenital myotonic dystrophy and other
      conditions with severe neonatal hypotonia.Management of CNM is mainly supportive,
      based on a multidisciplinary approach. Whereas the X-linked form due to MTM1
      mutations is often fatal in infancy, dominant forms due to DNM2 mutations and
      some cases of the recessive BIN1-related form appear to be associated with an
      overall more favourable prognosis.

PMID- 18817573
TI  - Apigenin and luteolin modulate microglial activation via inhibition of STAT1
      induced CD40 expression.
AB  - BACKGROUND: It is well known that most neurodegenerative diseases are associated
      with microglia-mediated inflammation. Our previous research demonstrates that the
      CD40 signaling is critically involved in microglia-related immune responses in
      the brain. For example, it is well known that the activation of the signal
      transducer and activator of transcription (STAT) signaling pathway plays a
      central role in interferon-gamma (IFN-gamma)-induced microglial CD40 expression.
      We and others have previously reported that microglial CD40 expression is
      significantly induced by IFN-gamma and amyloid-beta (A beta) peptide. Recent
      studies have shown that certain flavonoids possess anti-inflammatory and
      neuroprotective properties distinct from their well-known anti-oxidant effects.
      In particular, flavonoids, apigenin and luteolin have been found to be effective
      CD40 immunomodulators. METHODS: Cultured microglia, both N9 and primary derived
      lines, were treated with flavonoids in the presence of IFN-gamma and/or CD40
      ligation to assess any anti-inflammatory effects and/or mechanisms. CD40
      expression on microglia was analyzed by fluorescence activated cell sorting
      (FACS). Anti-inflammatory effects and mechanisms were confirmed by ELISA for
      interleukin-6 (IL-6) and TNF-alpha, lactate dehydrogenase (LDH) assay, and STAT1
      Western blotting. RESULTS: Apigenin and luteolin concentration-dependently
      suppressed IFN-gamma-induced CD40 expression. Apigenin and luteolin also
      suppressed microglial TNF-alpha and IL-6 production stimulated by IFN-gamma
      challenge in the presence of CD40 ligation. In addition, apigenin and luteolin
      markedly inhibited IFN-gamma-induced phosphorylation of STAT1 with little impact
      on cell survival. CONCLUSION: Our findings provide further support for apigenin
      and luteolin's anti-inflammatory effects and suggest that these flavonoids may
      have neuroprotective/disease-modifying properties in various neurodegenerative
      disorders, including Alzheimer's disease (AD).

PMID- 18817574
TI  - Evidence of increasing Leu-Phe knockdown resistance mutation in Anopheles gambiae
      from Niger following a nationwide long-lasting insecticide-treated nets
      implementation.
AB  - BACKGROUND: At the end of 2005, a nationwide long-lasting insecticide-treated net
      (LLIN) distribution targeting the most vulnerable populations was implemented
      throughout Niger. A large number of studies in Africa have reported the existence
      of anopheline populations resistant to various insecticides, partly due to
      knockdown resistance (kdr) mutations, but few operational wide-scale control
      programmes were coupled with the monitoring of such mutations. The distribution
      of the kdr-west (kdr-w) Leu-Phe mutation was studied in Anopheles gambiae s.l.
      populations from Niger and temporal variations were monitored following the
      nationwide LLIN implementation. METHODS: Mosquitoes were collected from 14
      localities during the wet seasons of 2005, 2006 and 2007 with additional sampling
      in the capital city, Niamey. After morphological identification of Anopheles
      gambiae s.l. specimens, DNA extracts were used for the determination of species
      and molecular forms of the Anopheles gambiae complex and for the detection of the
      kdr-w mutation. RESULTS: Around 1,500 specimens collected in the three
      consecutive years were analysed. All Anopheles arabiensis specimens analysed were
      homozygous susceptible, whereas the few Anopheles gambiae S forms exhibited a
      high overall kdr-w frequency. The M form samples exhibited a low overall kdr-w
      frequency before the LLIN distribution, that increased significantly in the two
      wet season collections following the LLIN distribution. Higher kdr frequencies
      were repeatedly noticed within host-seeking females compared to resting ones in
      indoor collections. In addition, preliminary results in M form urban populations
      from Niamey showed far higher kdr frequencies than in all of the rural sites
      studied. DISCUSSION: This study describes the first case of kdr mutation in
      Anopheles gambiae populations from Niger. It is suspected that the LLIN have
      caused the important temporal increase of kdr-w mutation observed during this
      study. While the kdr mutation is still found at a low level, this rapid increase
      could potentially lead to high kdr frequencies within a few years. CONCLUSION:
      These results are of prime importance in the effort to document multiple effects
      of operational control programmes on mosquito vectors, and to conceive
      sustainable control strategies for future malaria control programmes.

PMID- 18817575
TI  - Evaluation of Petrifilm Select E. coli Count Plate medium to discriminate
      antimicrobial resistant Escherichia coli.
AB  - BACKGROUND: Screening and enumeration of antimicrobial resistant Escherichia coli
      directly from samples is needed to identify emerging resistant clones and obtain
      quantitative data for risk assessment. Aim of this study was to evaluate the
      performance of 3M Petrifilm Select E. coli Count Plate (SEC plate) supplemented
      with antimicrobials to discriminate antimicrobial-resistant and non-resistant E.
      coli. METHOD: A range of E. coli isolates were tested by agar dilution method
      comparing the Minimal Inhibitory Concentration (MIC) for eight antimicrobials
      obtained by Mueller-Hinton II agar, MacConkey agar and SEC plates. Kappa
      statistics was used to assess the levels of agreement when classifying strains as
      resistant, intermediate or susceptible. RESULTS: SEC plate showed that 74% of all
      strains agreed within +/- 1 log2 dilution when comparing MICs with Mueller-Hinton
      II media. High agreement levels were found for gentamicin, ampicillin,
      chloramphenicol and cefotaxime, resulting in a kappa value of 0.9 and 100%
      agreement within +/- 1 log2 dilution. Significant variances were observed for
      oxytetracycline and sulphamethoxazole. Further tests showed that the observed
      discrepancy in classification of susceptibility to oxytetracycline by the two
      media could be overcome when a plate-dependent breakpoint of 64 mg/L was used for
      SEC plates. For sulphamethoxazole, SEC plates provided unacceptably high MICs.
      CONCLUSION: SEC plates showed good agreement with Mueller-Hinton II agar in MIC
      studies and can be used to screen and discriminate resistant E. coli for
      ampicillin, cephalothin, streptomycin, chloramphenicol, cefotaxime and gentamicin
      using CLSI standardized breakpoints, but not for sulphamethoxazole. SEC plates
      can also be used to discriminate oxytetracycline-resistant E. coli if a plate
      dependent breakpoint value of 64 mg/L is used.

PMID- 18817576
TI  - Sexual slavery without borders: trafficking for commercial sexual exploitation in
      India.
AB  - Trafficking in women and children is a gross violation of human rights. However,
      this does not prevent an estimated 800 000 women and children to be trafficked
      each year across international borders. Eighty per cent of trafficked persons end
      in forced sex work. India has been identified as one of the Asian countries where
      trafficking for commercial sexual exploitation has reached alarming levels. While
      there is a considerable amount of internal trafficking from one state to another
      or within states, India has also emerged as a international supplier of
      trafficked women and children to the Gulf States and South East Asia, as well as
      a destination country for women and girls trafficked for commercial sexual
      exploitation from Nepal and Bangladesh. Trafficking for commercial sexual
      exploitation is a highly profitable and low risk business that preys on
      particularly vulnerable populations. This paper presents an overview of the
      trafficking of women and girls for sexual exploitation (CSE) in India; identifies
      the health impacts of CSE; and suggest strategies to respond to trafficking and
      related issues.

PMID- 18817577
TI  - Transplacental transmission of Human Papillomavirus.
AB  - This paper aimed at studying the transplacental transmission of HPV and looking
      at the epidemiological factors involved in maternal viral infection. The
      following sampling methods were used: (1) in the pregnant woman, (a) genital; (b)
      peripheral blood; (2) in the newborn, (a) oral cavity, axillary and inguinal
      regions; (b) nasopharyngeal aspirate, and (c) cord blood; (3) in the placenta.
      The HPV DNA was identified using two methods: multiplex PCR of human beta-globin
      and of HPV using the PGMY09 and PGMY11 primers; and nested-PCR, which combines
      degenerated primers of the E6/E7 regions of the HPV virus, that allowed the
      identification of genotypes 6/11, 16, 18, 31, 33, 42, 52 and 58. Transplacental
      transmission was considered when type-specific HPV concordance was found between
      the mother, the placenta and the newborn or the mother and cord blood. The study
      included 49 HPV DNA-positive pregnant women at delivery. Twelve placentas (24.5%,
      n = 12/49) had a positive result for HPV DNA. Eleven newborn were HPV DNA
      positive in samples from the nasopharyngeal or buccal and body or cord blood. In
      5 cases (10.2%, n = 5/49) there was HPV type-specific agreement between
      genital/placenta/newborn samples. In one case (2%, n = 1/49) there was type
      specific HPV concordance between genital/cord blood and also suggested
      transplacental transmission. A positive and significant correlation was observed
      between transplacental transmission of HPV infection and the maternal variables
      of immunodepression history (HIV, p = 0.011). In conclusion the study suggests
      placental infection in 23.3% of the cases studied and transplacental transmission
      in 12.2%. It is suggested that in future HPV DNA be researched in the normal
      endometrium of women of reproductive age. The possible consequence of fetal
      exposure to HPV should be observed.

PMID- 18817578
TI  - Low wintertime vitamin D levels in a sample of healthy young adults of diverse
      ancestry living in the Toronto area: associations with vitamin D intake and skin
      pigmentation.
AB  - BACKGROUND: Vitamin D plays a critical role in bone metabolism and many cellular
      and immunological processes. Recent research indicates that concentrations of
      serum 25-hydroxyvitamin D [25(OH)D], the main indicator of vitamin D status,
      should be in excess of 75 nmol/L. Low levels of 25(OH)D have been associated with
      several chronic and infectious diseases. Previous studies have reported that many
      otherwise healthy adults of European ancestry living in Canada have low vitamin D
      concentrations during the wintertime. However, those of non-European ancestry are
      at a higher risk of having low vitamin D levels. The main goal of this study was
      to examine the vitamin D status and vitamin D intake of young Canadian adults of
      diverse ancestry during the winter months. METHODS: One hundred and seven (107)
      healthy young adults self-reporting their ancestry were recruited for this study.
      Each participant was tested for serum 25(OH)D concentrations and related
      biochemistry, skin pigmentation indices and basic anthropometric measures. A
      seven-day food diary was used to assess their vitamin D intake. An ANOVA was used
      to test for significant differences in the variables among groups of different
      ancestry. Linear regression was employed to assess the impact of relevant
      variables on serum 25(OH)D concentrations. RESULTS: More than 93% of the total
      sample had concentrations below 75 nmol/L. Almost three-quarters of the subjects
      had concentrations below 50 nmol/L. There were significant differences in serum
      25(OH)D levels (p < 0.001) and vitamin D intake (p = 0.034) between population
      groups. Only the European group had a mean vitamin D intake exceeding the current
      Recommended Adequate Intake (RAI = 200 IU/day). Total vitamin D intake (from diet
      and supplements) was significantly associated with 25(OH)D levels (p < 0.001).
      Skin pigmentation, assessed by measuring skin melanin content, showed an inverse
      relationship with serum 25(OH)D (p = 0.033). CONCLUSION: We observe that low
      vitamin D levels are more prevalent in our sample of young healthy adults than
      previously reported, particularly amongst those of non-European ancestry. Major
      factors influencing 25(OH)D levels were vitamin D intake and skin pigmentation.
      These data suggest a need to increase vitamin D intake either through improved
      fortification and/or supplementation.

PMID- 18817579
TI  - The greatest happiness of the greatest number? Policy actors' perspectives on the
      limits of economic evaluation as a tool for informing health care coverage
      decisions in Thailand.
AB  - BACKGROUND: This paper presents qualitative findings from an assessment of the
      acceptability of using economic evaluation among policy actors in Thailand. Using
      cost-utility data from two economic analyses a hypothetical case scenario was
      created in which policy actors had to choose between two competing interventions
      to include in a public health benefit package. The two competing interventions,
      laparoscopic cholecystectomy (LC) for gallbladder disease versus renal dialysis
      for chronic renal disease, were selected because they highlighted conflicting
      criteria influencing the allocation of healthcare resources. METHODS: Semi
      structured interviews were conducted with 36 policy actors who play a major role
      in resource allocation decisions within the Thai healthcare system. These
      included 14 policy makers at the national level, five hospital directors, ten
      health professionals and seven academics. RESULTS: Twenty six out of 36 (72%)
      respondents were not convinced by the presentation of economic evaluation
      findings and chose not to support the inclusion of a proven cost-effective
      intervention (LC) in the benefit package due to ethical, institutional and
      political considerations. There were only six respondents, including three policy
      makers at national level, one hospital director, one health professional and one
      academic, (6/36, 17%) whose decisions were influenced by economic evaluation
      evidence. CONCLUSION: This paper illustrates limitations of using economic
      evaluation information in decision making priorities of health care, perceived by
      different policy actors. It demonstrates that the concept of maximising health
      utility fails to recognise other important societal values in making health
      resource allocation decisions.

PMID- 18817580
TI  - Effect of excitatory and inhibitory agents and a glial inhibitor on optically
      recorded primary-afferent excitation.
AB  - The effects of GABA, excitatory amino-acid receptors antagonists and a glial
      metabolism inhibitor on primary-afferent excitation in the spinal dorsal horn
      were studied by imaging the presynaptic excitation of high-threshold afferents in
      cord slices from young rats with a voltage-sensitive dye. Primary afferent fibers
      and terminals were anterogradely labeled with a voltage-sensitive dye from the
      dorsal root attached to the spinal cord slice. Single-pulse stimulation of C
      fiber-activating strength to the dorsal root elicited compound action potential
      like optical responses in the superficial dorsal horn. The evoked presynaptic
      excitation was increased by the GABAA receptor antagonists picrotoxin and
      bicuculline, by glutamate receptor antagonists D-AP5 and CNQX, and by the glial
      metabolism inhibitor mono-fluoroacetic acid (MFA). The increase in presynaptic
      excitation by picrotoxin was inhibited in the presence of D-AP5, CNQX and MFA.
      Presynaptic modulation in the central terminal of fine primary afferents by
      excitatory and inhibitory amino acids may represent a mechanism that regulates
      the transmission of pain.

PMID- 18817581
TI  - Genetic and histological studies on the delayed systemic movement of Tobacco
      Mosaic Virus in Arabidopsis thaliana.
AB  - BACKGROUND: Viral infections and their spread throughout a plant require numerous
      interactions between the host and the virus. While new functions of viral
      proteins involved in these processes have been revealed, current knowledge of
      host factors involved in the spread of a viral infection is still insufficient.
      In Arabidopsis thaliana, different ecotypes present varying susceptibilities to
      Tobacco mosaic virus strain U1 (TMV-U1). The rate of TMV-U1 systemic movement is
      delayed in ecotype Col-0 when compared with other 13 ecotypes.We followed viral
      movement through vascular tissue in Col-0 plants by electronic microscopy
      studies. In addition, the delay in systemic movement of TMV-U1 was genetically
      studied. RESULTS: TMV-U1 reaches apical leaves only after 18 days post rosette
      inoculation (dpi) in Col-0, whereas it is detected at 9 dpi in the Uk-4 ecotype.
      Genetic crosses between Col-0 and Uk-4 ecotypes, followed by analysis of viral
      movement in F1 and F2 populations, revealed that this delayed movement correlates
      with a recessive, monogenic and nuclear locus. The use of selected polymorphic
      markers showed that this locus, denoted DSTM1 (Delayed Systemic Tobamovirus
      Movement 1), is positioned on the large arm of chromosome II. Electron microscopy
      studies following the virion's route in stems of Col-0 infected plants showed the
      presence of curved structures, instead of the typical rigid rods of TMV-U1. This
      was not observed in the case of TMV-U1 infection in Uk-4, where the observed
      virions have the typical rigid rod morphology. CONCLUSION: The presence of
      defectively assembled virions observed by electron microscopy in vascular tissue
      of Col-0 infected plants correlates with a recessive delayed systemic movement
      trait of TMV-U1 in this ecotype.

PMID- 18817582
TI  - Iota-Carrageenan is a potent inhibitor of rhinovirus infection.
AB  - BACKGROUND: Human rhinoviruses (HRVs) are the predominant cause of common cold.
      In addition, HRVs are implicated in the worsening of COPD and asthma, as well as
      the loss of lung transplants. Despite significant efforts, no anti-viral agent is
      approved for the prevention or treatment of HRV-infection. RESULTS: In this study
      we demonstrate that Iota-Carrageenan, a sulphated polysaccharide derived from red
      seaweed, is a potent anti-rhinoviral substance in-vitro. Iota-Carrageenan reduces
      HRV growth and inhibits the virus induced cythopathic effect of infected HeLa
      cells. In addition, Iota-Carrageenan effectively prevents the replication of
      HRV1A, HRV2, HRV8, HRV14, HRV16, HRV83 and HRV84 in primary human nasal
      epithelial cells in culture. The data suggest that Iota-Carrageenan acts
      primarily by preventing the binding or the entry of virions into the cells.
      CONCLUSION: Since HRV infections predominately occur in the nasal cavity and the
      upper respiratory tract, a targeted treatment with a product containing Iota
      Carrageenan is conceivable. Clinical trials are needed to determine whether Iota
      Carrageenan-based products are effective in the treatment or prophylaxis of HRV
      infections.

PMID- 18817584
TI  - Combating ageism.

PMID- 18817585
TI  - An outbreak of hepatitis A in recently vaccinated students from ice snacks made
      from contaminated well water.
AB  - On 30 May 2006, township S in Sichuan Province, China, reported an outbreak of
      hepatitis A (HA) in students who had recently received HA vaccine. The concern
      was raised that the vaccine had caused the outbreak. We attempted to identify the
      source of infection and mode of transmission. A HA case was defined as onset of
      jaundice or anorexia since 1 April 2006 with a twofold elevation of alanine
      aminotransferase (ALT) and anti-HA virus-IgM in a resident of or visitor to the
      township. Exposures to vaccine and snacks of 90 case-students to those of 107
      control-students were compared. Thirty-four per cent of cases ate ice slush
      compared to 4.7% of controls (OR 4.1), and 51% of cases ate snow cones compared
      to 17% of controls (OR 8.3). The ice snacks were made with well water. HA virus
      RNA was detected by reverse transcription-polymerase chain reaction from
      patients' blood and well water. Untreated well water poses important dangers to
      the public in areas where piped, potable water is available.

PMID- 18817586
TI  - Large Salmonella Enteritidis outbreak with prolonged transmission attributed to
      an infected food handler, Texas, 2002.
AB  - In March 2002, an outbreak of Salmonella Enteritidis (SE) infections occurred at
      a convention centre in Dallas, Texas and continued for 6 weeks. We conducted
      epidemiological studies, obtained clinical and environmental cultures, and
      interviewed employees to identify risk factors for infection. From 17 March-25
      April 2002, the implicated hotel kitchen catered 41 multi-day conferences
      attended by 9790 persons. We received 617 illness reports from residents of 46
      states. Sauces or items served with sauces were implicated in three cohort
      studies. SE phage-type 8 was identified as the agent. Eleven food service
      employees, including one who prepared sauces and salsa, had stool cultures that
      yielded SE. Although the original source was not determined, prolonged
      transmission resulted in the largest food handler-associated outbreak reported to
      date, affecting persons from 46 US states. Transmission ended with implementation
      of policies to screen food handlers and exclude those whose stool cultures
      yielded salmonellas.

PMID- 18817587
TI  - Detection of antibodies against Fasciola hepatica in cirrhotic patients from
      Peru.
AB  - The prevalence of Fasciola hepatica infection, in endemic countries, in patients
      with established cirrhosis is unknown. We hypothesized that, in endemic
      countries, the presence of fascioliasis may be detected in a serum pool of
      cirrhotic patients. Forty-four previously stored serum samples of patients with
      established liver cirrhosis, in the Hospital Nacional Cayetano Heredia in Lima,
      Peru, were collected from 1998 to 2003 and assessed for hepatitis B, C and
      fascioliasis antibodies (Fas2 ELISA). Hepatitis B surface antigen (HBsAg) was
      positive in 8.8% (n = 34), hepatitis B core antibody (anti-HBc) in 32.5% (n =
      34), hepatitis C antibodies (anti-HCV) in 9.1% (n = 33), and 9.1% (n = 44) were
      Fas2 ELISA positive. This disease is an example of an emerging tropical infection
      which can be present in chronic liver diseases, requiring greater clinician
      awareness especially in endemic rural areas. Further clinical studies are
      warranted.

PMID- 18817588
TI  - Public health nutrition--moving from rhetoric to results.

PMID- 18817590
TI  - Out of the box.

PMID- 18817591
TI  - Clifton Briggs Leech: first director of the pediatric cardiac clinic at the Johns
      Hopkins Harriet Lane Home for Invalid Children.
AB  - The history of Helen Taussig is well known. Contrary to popular belief, however,
      she was not the first director of the pediatric cardiology clinic at the Harriet
      Lane Home for Invalid Children. She was second director, succeeding Clifton B.
      Leech. Edwards A. Park, Chief of Pediatrics at Johns Hopkins, appointed Leech the
      first director of the pediatric cardiac clinic in the fall of 1928. In this
      vignette, I summarize the contributions of Clifton Leech to the development of
      paediatric cardiology.

PMID- 18817592
TI  - Diagnosis, evaluation, and management of the hypertensive disorders of pregnancy.
AB  - OBJECTIVE: This guideline summarizes the quality of the evidence to date and
      provides a reasonable approach to the diagnosis, evaluation, and treatment of the
      hypertensive disorders of pregnancy (HDP). EVIDENCE: The literature reviewed
      included the original HDP guidelines and their reference lists and an update from
      1995. Using key words, Medline was searched for literature published between 1995
      and 2007. Articles were restricted to those published in French or English.
      Recommendations were evaluated using the criteria of the Canadian Task Force on
      Preventive Health Care (Table 1). SPONSORS: This guideline was developed by the
      Society of Obstetricians and Gynaecologists of Canada and was partly supported by
      an unrestricted educational grant from the British Columbia Perinatal Health
      Program (formerly the British Columbia Reproductive Care Program or BCRCP). The
      Canadian Hypertension Society provided assistance with the literature search and
      some travel support for one author. Much of the Canadian research cited in this
      document has been funded by the Canadian Institutes of Health Research. The
      potential for ongoing support is gratefully acknowledged.

PMID- 18817593
TI  - The social organization of representations of history: the textual accomplishment
      of coming to terms with the past.
AB  - This paper is concerned with the social organization of collective memory and
      representations of history in the context of how post-communist democracies
      reckon with former regimes. It specifically centres on the textual accomplishment
      of coming to terms with the past in the 'Tismaneanu Report' condemning Communism
      in Romania. The focus is on how the Report displays and shapes the ideological
      contours of coming to terms with the past around a particular 'social
      representation' of history. Several constitutive features of the Report that
      facilitate bringing off a particular 'representation of history' are identified:
      (a) the construction of a practical framework for the inquiry as a matter of
      public concern and attention; (b) the production of 'Communism' as an empirical
      category with uniquely bound features; and (c) the structuring of time by
      bringing together a political agenda and national identity. The present argument
      tries to place representations of history (and coming to terms with the past) as
      something in need of constitution rather than simply relied on. It is suggested
      that a conception of coming to terms with the past as a textual accomplishment
      may lead to a fuller appreciation of the structure, function and salience of
      representations of history as integral part of moral/political/legal courses of
      action.

PMID- 18817594
TI  - Second nature.
AB  - Are ontological meanings somehow sacrosanct in arguments concerning psychology -
      particularly those scored by discursive accounts of human being? Or is the
      purposeful deferment of ontological concerns in discursive psychology (DP)
      another instance of method-fetishism (Koch, 1981)? Shotter's (1995) understanding
      of joint action and Chouliaraki's (2002) critical realist account of social
      action combine to support an alternate position to the predominant discursive
      psychological approach informed by epistemological constructionism (DPEC). The
      DPEC position is here contrasted with a discursive psychological approach
      informed by ontological constructionism (DPOC). Via this distinction, a path for
      future discursive psychological studies is charted, one which values
      understanding the kinds of practical-moral knowledges (Shotter, 1993) available
      to people in accounting for themselves and their actions as psychosocial agents.
      Contrary to claims that the DPEC/DPOC distinction is supercilious (Edley, 2001)
      or oxymoronic (Drewery, 2000), the importance of debating what ontology can mean
      for psychology is herein seen as central to the pursuit of personal, relational
      and collective wellness in contemporary life.

PMID- 18817595
TI  - 'I hope we won't have to understand racism one day': researching or reproducing
      'race' in social psychological research?
AB  - This paper examines the reification and problemization of 'race' in Psychological
      research in both influential studies in the field and in my empirical work. The
      main argument is that we need to examine how representations of 'race' are
      assumed, produced and contested in research practice. This argument is made by
      (a) showing how research in the area adopts everyday representations of 'race' as
      essentialized and (b) with an illustration of the construction of 'race' within
      my study. This study explores how children in a predominantly white setting
      accept and contest representations that race. twenty two children from a range of
      cultural backgrounds volunteered to discuss their views and experiences of 'race'
      and racism in a naturalistic research activity. The analysis reveals that
      racialized difference is something that is constructed as both 'real' - in that
      it can be seen, touched and even caught from 'the other' and simultaneously
      something that is constructed, imposed and damaging. This highlights the
      possibilities for racialized others to take up positions as agents and not (only)
      as objects of the racializing and racist gaze, and so presents the case for
      thinking, debating and researching beyond reifying representations of 'race'.
      This has important lessons for social psychology: namely, we cannot continue to
      take racial categorization as a naturalistic or self-evident aspect of the social
      worlds that our discipline plays an important role in constructing and defending.

PMID- 18817596
TI  - Do humans prefer altruistic mates? Testing a link between sexual selection and
      altruism towards non-relatives.
AB  - Humans are often seen as unusual in displaying altruistic behaviour towards non
      relatives. Here we outline and test a hypothesis that human altruistic traits
      evolved as a result of sexual selection. We develop a psychometric scale to
      measure mate preference towards altruistic traits (the MPAT scale). We then seek
      evidence of whether mate choice on the basis of altruistic traits is present and
      find it in one study (N=170 couples). We also predict that a stronger female
      MPAT, as measured by responses to the MPAT scale, will be expressed - a result
      found in all three studies (Ns=380, 340, and 398). Both sets of results are
      consistent with the hypothesized link between human altruism towards non
      relatives and sexual selection.

PMID- 18817597
TI  - A randomized, comparative study of supervised and unsupervised artesunate
      amodiaquine, for the treatment of uncomplicated malaria in Ghana.
AB  - Although the use of artesunate-amodiaquine treatment is growing in Africa, data
      on its effectiveness are limited. In only the second published comparison of
      supervised and unsupervised treatments with this combination, Ghanaian children
      with uncomplicated malaria have recently been investigated in an open-label,
      randomized, comparative study. Children aged 6-120 months attending the Navrongo
      War Memorial hospital between November 2005 and December 2006 were enrolled if
      they had uncomplicated Plasmodium falciparum malaria and at least one of their
      parents/guardians gave their informed consent. Overall, 638 patients were
      screened, 357 were found to have P. falciparum infection, and 308 of these
      satisfied the other selection criteria and were enrolled. The subjects were
      divided randomly into two treatment arms. All the children were scheduled to
      receive 10 mg amodiaquine/kg and 4 mg artesunate/kg daily for 3 days but only 154
      (the 'supervised') were given all their treatments in hospital, with each dose
      directly observed. Although the other 154 children (the 'unsupervised') were
      given their first dose in hospital, under supervision, they were then sent home
      with the tablets they required to complete treatment. Study participation lasted
      for 28 days, with follow-up on days 3, 7, 14, 21 and 28. During follow-up,
      axillary temperatures, any emergent signs and symptoms, and concomitant drug
      consumption were recorded and haemoglobin concentrations and malarial
      parasitaemias and gametocytaemias were measured. All but seven of the 308
      subjects completed the study. At enrolment the subjects had a mean age of 45.0
      months, a mean weight of 14.8 kg, a mean axillary temperature of 37.9 degrees C
      and a geometric mean parasitaemia of 11,367 asexual stages/microl. About 55% of
      the children investigated were girls. There were no significant baseline
      difference between the two treatment arms. Although there was also no difference
      in the clearance of fever and parasitaemia between the two arms by day 14, a
      supervised child was significantly more likely to show an adequate clinical and
      parasitological response, by day 21 (91.3% v. 84.1%; P= 0.05) or day 28 (80.0% v.
      64.9%; P<0.01), than an unsupervised child. The reported adverse effects
      following treatment and the trend in haemoglobin recovery were, however, similar
      in the two arms. Although artesunate-amodiaquine appeared very effective in the
      treatment of uncomplicated P. falciparum malaria in children, whether supervised
      or not, it appears that supervised treatment provided stronger prevention against
      re-infection and recrudescence. At least in the present study, treatment at home,
      without medical supervision, probably led to relatively poor compliance.

PMID- 18817598
TI  - Asymptomatic human carriers of Leishmania infantum: possible reservoirs for
      Mediterranean visceral leishmaniasis in southern Iran.
AB  - Over the last decade, the incidence of visceral leishmaniasis (VL) has increased
      in many districts of the province of Fars, in southern Iran. Recent
      epidemiological reports indicate that asymptomatic human infections with
      Leishmania infantum (the causative agent of VL throughout the Mediterranean
      basin) occur more frequently in Iran than was previously believed. Between 2004
      and 2006, blood samples were collected from 802 apparently healthy subjects from
      communities, in the north-west and south-east of Fars province, where VL cases
      had been recorded. Each of these samples was tested for anti-Leishmania
      antibodies, in direct agglutination tests (DAT), and for L. infantum kinetoplast
      DNA, in PCR-based assays. Of the 426 subjects from north-western Fars, eight
      (1.9%) were found seropositive and 68 (16.0%) PCR-positive. The corresponding
      values for the 376 subjects from south-eastern Fars were lower, with five (1.3%)
      seropositive and 32 (8.5%) PCR-positive. Of the 100 PCR-positive subjects, 18
      (18.0%) each lived in a household in which there had been a case of VL, and six
      (6.0%) had had VL themselves (in each case, more than a year before the blood
      sampling for the present study). Although 21 of the PCR-positives have now been
      followed-up for at least 18 months, none has developed symptomatic VL. Since
      positivity in the PCR-based assay probably indicated the presence of L. infantum
      amastigotes in the peripheral blood of 12.5% of the subjects, it is clear that
      asymptomatic human carriers of L. infantum are quite common in the study areas
      and probably act as reservoirs in the transmission of the parasite, to humans and
      to dogs, by sandflies.

PMID- 18817599
TI  - Giardia infections in Cuban children: the genotypes circulating in a rural
      population.
AB  - Stool samples containing Giardia duodenalis cysts were collected from 95 primary
      school children in central Cuba, and preserved by storing at -20 degrees C in 70%
      ethanol. Clinical data were collected for each child. Although 57% of the
      children were asymptomatic, the remaining 43% each reported between one and three
      symptoms. Following cyst quantification and isolation, molecular analyses were
      attempted on all cyst isolates, with the focus on the parasite's beta-giardin and
      glutamate-dehydrogenase (gdh) genes. Unfortunately, the cyst-preservation
      procedure appeared to have a deleterious effect on the cysts, since genotyping
      data could only be obtained for 20 of the 95 isolates. These data indicated,
      however, an approximately equal distribution between assemblage A (nine isolates)
      and assemblage B (11 isolates). Children found to be excreting relatively large
      numbers of cysts were more likely to be symptomatic than children who were
      excreting fewer cysts, and children with Giardia isolates from assemblage B were
      more likely to have symptomatic infections than children with isolates from
      assemblage A. Although considerable sequence variability was seen in the
      assemblage-B isolates, the assemblage-A isolates were relatively genetically
      homogeneous. This is the first publication from the Caribbean in which the
      Giardia genotypes circulating within the population have been identified, the
      first from the Americas providing information on associations between clinical
      presentation and the assemblage of the infecting Giardia, and the first to
      indicate that levels of cyst excretion may have clinical significance.

PMID- 18817600
TI  - The use of a nested PCR-RFLP technique, based on the parasite's 18S ribosomal
      RNA, to characterise Cryptosporidium isolates from HIV/AIDS patients.
AB  - Since there have been few studies on human cryptosporidiosis in Iran, attempts
      were made to identify Cryptosporidium isolates from HIV-positive Iranians, to
      genotype level. A nested PCR (based on a fragment of the parasite's 18S ribosomal
      RNA gene) was first used to see if faecal samples from 35 HIV-positive patients
      (of whom 17 had apparently been found smear-positive for Cryptosporidium oocysts)
      contained Cryptosporidium. Twenty-one of the samples (including all 17 of those
      that appeared smear-positive) were found PCR-positive. Each of these 21 samples
      was then investigated further, by RFLP analysis in which the amplicons from the
      secondary PCR were digested with VspI. Curiously, although HIV-infected
      individuals are known to be susceptible to infection with a wide range of
      Cryptosporidium genotypes, all the Iranian subjects of the present study were
      found to be infected with C. hominis (71%) or C. parvum (29%).

PMID- 18817601
TI  - A retrospective analysis of human cystic echinococcosis in Hamedan province, an
      endemic region of Iran.
AB  - In a retrospective investigation, the medical files of the patients who, between
      1992 and 2006, underwent surgery for the treatment of cystic echinococcosis (CE)
      in one of the three university hospitals in Hamedan province, in western Iran,
      were explored. Of the 179 patients involved, 44.1% were male and 55.9% female,
      giving a male/ female ratio of 0.79. The mean annual surgical incidence of CE in
      the catchment areas of the study hospitals was estimated to be 1.33
      cases/100,000. Although most of Hamedan's population is urban (53.02% at the last
      census, in 1997), most (57.5%) of the patients lived in rural areas (P<0.05).
      Among the CE cases, housewives (47.3%), farmers (16.6%) and labourers (16.0%)
      were over-represented compared with the frequencies of these occupations in the
      general population of the region (P<0.05 for each). Most of the CE cases were
      aged 20-39 years (35.8%) or 40-59 years (29.0%) and most had liver cysts, either
      alone (60.9%) or with cysts in other sites (9.5%), although 19.6% of the cases
      appeared only to have lung cysts. Overall, 90.5% of the cases showed single-organ
      involvement. Liver involvement was 3.3-fold more common than lung involvement,
      the ratio between cases with liver cysts and those with lung cysts generally
      increasing with age (from 1.6 for the cases aged <20 years to 5.6 among the cases
      aged 40-59 years). The most common clinical symptoms were abdominal pain and/or a
      sensation of abdominal mass in those with hepatic CE, and chest pain, cough,
      dyspnoea and/or haemoptysis in those with pulmonary CE. Although 72% of the cases
      each had a single cyst, 19.6% had two cysts each and 8.4% each had at least three
      cysts. Only three (1.7%) of the cases had had previous surgery for CE. Diagnosis
      of CE in Hamedan province is largely dependent on ultrasonography and computed
      tomography. Together, these results confirm that CE is endemic in the province
      and indicate that certain occupations (housewife, farmer and labourer) and/or
      rural life are risk factors.

PMID- 18817602
TI  - Epidemic transmission of intestinal schistosomiasis in the seasonal part of the
      Okavango Delta, Botswana.
AB  - A well documented epidemic of human intestinal schistosomiasis caused by
      Schistosoma mansoni occurred at Maun in the seasonal part of the Okavango Delta,
      Botswana, building from very few cases in the 1950s and early 1960s to a peak
      prevalence of >80% in the 1980s. A retrospective analysis was performed on all
      available records of the prevalence of S. mansoni in the Maun area and the
      corresponding flow records of the Thamalakane River. These revealed a
      statistically significant correlation between prevalence and flow, but only when
      a lag period was introduced. The correlation was greatest with a lag period of 5
      6 years between the rise and fall of discharge and the rise and fall of
      transmission. Since the hydrological events in the delta follow a cyclical
      pattern, another epidemic around 2020 appears likely.

PMID- 18817603
TI  - Application of a circulating-cathodic-antigen (CCA) strip test and real-time PCR,
      in comparison with microscopy, for the detection of Schistosoma haematobium in
      urine samples from Ghana.
AB  - In the detection of parasitic infection, the traditional methods based on
      microscopy often have low sensitivity and/or specificity compared with the newer,
      molecular tests. An assay based on real-time PCR and a reagent strip test for
      detecting circulating cathodic antigen (CCA) have both now been compared with
      urine filtration and microscopy, in the detection of Schistosoma haematobium
      infections. Urine samples, obtained from 74 'cases' in areas of Ghana with
      endemic S. haematobium and 79 'controls' from non-endemic areas, were each
      checked using the three methods. With the results of the filtration and
      microscopy taken as the 'gold standard', real-time PCR was found to be 100%
      specific and 89% sensitive whereas the CCA strips were 91% specific and 41%
      sensitive. With the samples found to contain > or =50 eggs/10 ml (indicating
      relatively intense infections), the sensitivities of the PCR and CCA were higher,
      at 100% and 62%, respectively. As expected, egg counts were negatively correlated
      with the number of amplification cycles needed, in the PCR, to give a signal that
      exceeded the background (r=-0.38; P<0.01). Although the real-time PCR and CCA
      strip tests are very different, both show promise in the detection of S.
      haematobium infections. The PCR has optimal specificity and high sensitivity but
      the specificity of the CCA strips and the sensitivity of both tools could still
      be improved. A more thorough re-evaluation of the sensitivity and specificity of
      microscopy and these newer diagnostic methods, with an estimation of the cost
      effectiveness of each technique, is recommended.

PMID- 18817604
TI  - Bacterial infections in children with visceral leishmaniasis: observations made
      in Kerman province, southern Iran, between 1997 and 2007.
AB  - Cases of human visceral leishmaniasis (VL) are often found to have bacterial
      infections. Between 1997 and 2007, 60 cases of VL were admitted to the paediatric
      ward of the Afzalipour Medical Centre, which forms part of the Kerman University
      of Medical Sciences, in southern Iran. On admission, the 60 cases (39 boys and 21
      girls), each of which was confirmed by the demonstration of amastigotes in a bone
      marrow aspirate, had a mean (S.D.) age of 48.8 (44.4) months and a mean (S.D.)
      erythrocyte sedimentation rate of 53.2 (34.2) mm/h. Twenty-five (42%) of the
      cases (14 boys and 11 girls) were found to have bacterial infections. Urinary
      infections (seen in 36% of the cases with bacterial infection) were the most
      common, followed by blood (28%), respiratory (16%), gastro-intestinal (12%) and
      skin infections (8%). Despite treatment of all the VL cases with meglumine
      antimoniate, four (7%) died on the paediatric ward, all four having concurrent
      bacterial infections. The leucopenia and immunosuppression associated with VL
      probably facilitate the development of fatal bacterial co-infections. The prompt
      diagnosis and treatment of both the VL and any bacterial co-infections should
      therefore reduce mortality among VL cases.

PMID- 18817605
TI  - The role of prednisolone in reducing limb oedema in children bitten by green pit
      vipers: a randomized, controlled trial.
AB  - When green pit vipers (GPV), which are common venomous snakes in Thailand, bite
      humans they cause coagulopathy as well as local tissue oedema. The use of
      steroids to reduce such oedema is controversial. The role of low, oral doses of
      prednisolone in the treatment of GPV bites in children has therefore now been
      assessed, in a randomized, double-blinded, placebo-controlled, clinical trial in
      Bangkok. Overall, 43 children aged 3-15 years, each with a recent GPV bite to one
      limb, were randomly assigned to receive oral prednisolone (1 mg/kg.day) or
      placebo for 3 days, without antivenom or prophylactic antibiotics. The degree of
      limb oedema was assessed, immediately before the first dose and then daily, by
      measuring the limb circumference around the fang marks. By 72 h post-bite, both
      treatment groups showed significant decreases in the level of their limb oedema.
      Since, at each time-point, the patients in the two groups showed similar levels
      of limb oedema (and of reduction in such oedema), there appeared to be no benefit
      from the use of the prednisolone.

PMID- 18817606
TI  - Detection of plasmid-encoded bla-CTX-M-15 and bla-TEM-1 genes in a Lebanese
      Salmonella isolate that produces extended-spectrum beta-lactamase.

PMID- 18817607
TI  - Beyond infertility: breakthroughs in reproductive medicine and technology.
      Abstracts of the 4th World Congress of World Association of Reproductive Medicine
      (WARM). September 23-26, 2008. Guadalajara, Mexico.

PMID- 18817617
TI  - Synergistic effects of prostaglandin E1 and lithium in a rat model of cerebral
      ischemia.
AB  - AIM: Heat shock proteins (HSPs) are important regulators of cellular survival and
      exert neuroprotective effects against cerebral ischemia. Both prostaglandin E1
      (PGE1) and lithium have been reported to protect neurons against ischemic injury.
      The present study was undertaken to examine if lithium could potentiate the
      neuroprotection of PGE1 against cerebral ischemia, and if the synergetic effects
      take place at the level of HSPs. METHODS: Brain ischemia was induced by a
      permanent middle cerebral artery occlusion (pMCAO) in rats. Rats were pretreated
      with subcutaneous injection of lithium for 2 d and a single intravenous
      administration of PGE1 immediately after ischemic insult. Cerebrocortical blood
      flow of each group was closely monitored prior to onset of ischemia, 5 min, 15
      min, 30 min and 60 min after surgical operation. Body temperature was measured
      before, 5 min, 2 h and 24 h after the onset of pMCAO. The infarct volume, brain
      edema and motor behavior deficits were analyzed 24 h after ischemic insult.
      Cytoprotective HSP70 and heme oxygenase-1 (HO-1) in the striatum of the
      ipsilateral hemisphere were detected by immunoblotting. Brain sections from the
      striatum of the ipsilateral hemisphere were double-labeled with the anti-HSP70
      antibody and 4,6-diamidino-2-phenylindole (DAPI). RESULTS: Treatment with PGE1 (8
      and 16 microg/kg, iv) or lithium (0.5 mEq/kg, sc) alone reduced infarct volume,
      neurological deficits and brain edema induced by focal cerebral ischemia in rats.
      Moreover, a greater neuroprotection was observed when PGE1 and lithium were given
      together. Co-administration of PGE1 and lithium significantly upregulated
      cytoprotective HSP70 and HO-1 protein levels. CONCLUSION: Lithium and PGE1 may
      exert synergistic effects in treatment of cerebral ischemia and thus may have
      potential clinical value for the treatment of stroke.

PMID- 18817618
TI  - Protective effects of TREK-1 against oxidative injury induced by SNP and H2O2.
AB  - AIM: TREK-1 (TWIK-related K+ channel-1) is a 2-pore-domain K+ channel subtype.
      The present study investigated the role of TREK-1 in cell death induced by
      oxidative stress. METHODS: The cell viability of wild-type Chinese hamster ovary
      (CHO) and TREK-1-transfected CHO cells (TREK-1/CHO cells) was measured using 3
      (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in the
      presence of sodium nitroprusside (SNP) or hydrogen peroxide (H2O2). Apoptosis of
      wild-type CHO and TREK-1/CHO cells was detected using Hoechst33342 staining.
      RESULTS: Both SNP and H2O2 caused dose- and time-dependent growth inhibition of
      wild-type CHO and TREK-1/ CHO cells. Following a 12 h exposure to SNP, the 50%
      inhibition (IC(50)) values for wild-type CHO and TREK-1/CHO cells were calculated
      as 0.69 mmol/L and 1.14 mmol/L, respectively. The IC(50) values were 0.07 mmol/L
      and 0.09 mmol/L in H2O2-treated wild-type CHO and TREK-1/CHO cells, respectively,
      following 12 h exposure to H2O2. Moreover, SNP/H2O2 induced less apoptosis in
      TREK-1/ CHO cells than that in wild-type CHO cells (P<0.05). CONCLUSION: The
      results demonstrated that TREK-1 played a protective role against oxidative
      injury.

PMID- 18817619
TI  - Effects of endogenous sulfur dioxide on monocrotaline-induced pulmonary
      hypertension in rats.
AB  - AIM: The present study aimed to explore the protective effect of endogenous
      sulfur dioxide (SO2) in the development of monocrotaline (MCT)-induced pulmonary
      hypertension (PH) in rats. METHODS: Forty Wistar rats were randomly divided into
      the MCT group receiving MCT treatment, the MCT+L-aspartate-beta- hydroxamate
      (HDX) group receiving MCT plus HDX treatment, the MCT+SO2 group receiving MCT
      plus SO2 donor treatment, and the control group. Mean pulmonary artery pressure
      (mPAP) and structural changes in pulmonary arteries were evaluated. SO2 content,
      aspartate aminotransferase activity, and gene expression were measured.
      Superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT),
      reduced glutathione (GSH), oxidized glutathione, and malondialdehyde (MDA) levels
      were assayed. RESULTS: In the MCT-treated rats, mPAP and right ventricle/(left
      ventricle+septum) increased significantly (P<0.01), pulmonary vascular structural
      remodeling developed, and SOD, GSHPx, CAT, GSH, and MDA levels of lung
      homogenates significantly increased (P<0.01) in association with the elevated SO2
      content, aspartate aminotransferase activity, and gene expression, compared with
      the control rats. In the MCT+HDXtreated rats, lung tissues and plasma SO2 content
      and aspartate aminotransferase activities decreased significantly, whereas the
      mPAP and pulmonary vascular structural remodeling were markedly aggravated with
      the decreased SOD, CAT, and GSH levels of lung tissue homogenates compared with
      the MCT-treated rats (P<0.01). In contrast, with the use of a SO2 donor, the
      pulmonary vascular structural remodeling was obviously lessened with elevated
      lung tissue SOD, GSH-Px, and MDA content, and plasma SOD, GSH-Px, and CAT levels.
      CONCLUSION: Endogenous SO2 might play a protective role in the pathogenesis of
      MCT-induced PH and promote endogenous antioxidative capacities.

PMID- 18817620
TI  - Altered ATP-sensitive potassium channels may underscore obesity-triggered
      increase in blood pressure.
AB  - AIM: To determine whether ATP-sensitive potassium channels are altered in VSMC
      from arotas and mesenteric arteries of obese rat, and their association with
      obesity-triggered increase in blood pressure. METHODS: Obesity was induced by 24
      weeks of high-fat diet feeding in male Sprague-Dawley rats. Control rats were fed
      with standard laboratory rat chow. Blood pressure and body weight of these rats
      were measured every 4 weeks. At the end of 24 weeks, K(ATP) channelmediated
      relaxation responses in the aortas and mesenteric arteries, K(ATP) channel
      current, and gene expression were examined, respectively. RESULTS: Blood pressure
      and body weight were increased in rats fed with high-fat diet. K(ATP)
      channelmediated relaxation responses, currents, and K(ATP) expression in VSMC of
      both aortas and mesenteric arteries were inhibited in these rats. CONCLUSION:
      Altered ATP-sensitive potassium channels in obese rats may underscore obesity
      triggered increase in blood pressure.

PMID- 18817621
TI  - Stimulation of Na+-Ca2+ exchange by purified antibody against alpha-2 repeat of
      Na+-Ca2+ exchanger in rat cardiomyocytes.
AB  - AIM: The aim of the present study was to investigate the effect of the antibody
      against alpha-2 repeat on Na+-Ca2+ exchanger (NCX) current (I(Na/Ca)). To
      evaluate the functional specificity of this antibody, its effects on L-type Ca2+
      current (I(Ca,L)), voltage-gated Na+ current (I(Na)) and delayed rectifier K+
      current (I(K)) were also observed. METHODS: The whole-cell patch-clamp technique
      was used in this study. RESULTS: The antibody against alpha-2 repeat augmented
      both the outward and inward Na+-Ca2+ exchanger current concentration-dependently,
      with EC(50) values of 27.9 nmol/L and 24.7 nmol/L, respectively. Meanwhile, the
      antibody could also increase I(Ca,L) in a concentration-dependent manner with the
      EC(50) of 33.6 nmol/L. Effects of the antibody on I(Na) and I(K) were not
      observed in the present study. CONCLUSION: The present results suggest that
      antibody against alpha-2 repeat is a stimulating antibody to NCX and could also
      increase I(Ca,L) in a concentration-dependent manner, but did not have an obvious
      effect on I(Na) and I(K).

PMID- 18817622
TI  - Tissue-specific effects of atorvastatin on 3-hydroxy-3-methylglutarylcoenzyme A
      reductase expression and activity in spontaneously hypertensive rats.
AB  - AIM: Cardiovascular remodeling is closely associated with cholesterol and is
      attenuated by statins. The spontaneously hypertensive rat (SHR) has a low serum
      cholesterol level and evident cardiovascular remodeling. The aims of the present
      study were to characterize the effects of atorvastatin on tissue cholesterol
      content and 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase expression
      and activity in four tissues from SHR: liver, heart, aorta and kidney. METHODS:
      SHR and normotensive Wistar-Kyoto rats (WKY) were treated daily with atorvastatin
      (50 mg/kg) for 8 weeks. Cholesterol levels of serum and tissues (liver, heart,
      aorta and kidney) were determined by commercial enzymatic methods. Western blot
      analysis and high performance liquid chromatogram (HPLC) were used to assay the
      expression and activity of enzyme respectively. RESULTS: Treatment with
      atorvastatin decreased cholesterol content and HMGCoA reductase expression and
      activity in all four tissues of SHR. However, in WKY, atorvastatin only altered
      HMG-CoA reductase in liver, where the protein expression was upregulated but the
      enzyme activity was decreased. CONCLUSION: The present study demonstrates that
      the effects of atorvastatin on tissue cholesterol content and HMG-CoA reductase
      are strain- and tissue-specific.

PMID- 18817623
TI  - Identification of higenamine in Radix Aconiti Lateralis Preparata as a beta2
      adrenergic receptor agonist1.
AB  - AIM: To screen beta2-adrenergic receptor (beta2-AR) agonists from Radix Aconiti
      Lateralis Preparata (RALP) as potential drug leads for asthma using a sensitive
      cell-based agonist assay. METHODS: The beta2-AR gene was stably expressed by
      Chinese hamster ovary (CHO) cells also stably expressing a cyclic adenosine
      monophosphate (AMP) response element-linked enhanced green fluorescent protein
      reporter gene. The cells were used to screen agonists from high-performance
      liquid chromatographic fractions of an extract of RALP. The fraction with the
      highest activity was selected for further compound isolation and the study of the
      structure-activity relationship. Its active compound was further identified by
      chromatography and mass spectrometry. RESULTS: Bioactivity-directed fractionation
      of the crude extract of RALP led to the isolation and characterization of the
      effective compound, namely hignamine. It could dose-dependently relax the
      isolated guinea pig trachea strip precontraction with acetylcholine with EC(50)
      value of (2.60+/-0.36)x10(-5) mol/L. Further in vivo studies also displayed that
      hignamine could protect experimental asthma model induced by histamine in guinea
      pigs to prolong the latent periods of asthma. CONCLUSION: Hignamine, as a beta2
      AR agonist existing in the extract of RALP, is the key compound contributing to
      the successful relief of the bronchoconstriction.

PMID- 18817624
TI  - Acetamide-45 inhibited hyperresponsiveness and airway inflammation in mice partly
      depending on phosphodiesterase activity suppression.
AB  - AIM: Asthma is characterized as a chronic inflammatory disorder of the airways.
      Phosphodiesterases (PDE), which hydrolyze cAMP, are considered to play important
      roles in asthma. We previously reported that acetamide-45 could inhibit cAMP-PDE
      activity, and histamine- and methacholine-induced contractions of isolated guinea
      pig trachea. The purpose of this study is to determine whether this agent could
      suppress allergic-induced airway hyperresponsiveness (AHR) and airway
      inflammation in allergic mice. METHODS: A mouse model for asthma was used to
      investigate acetamide-45 on the airway lesions compared with glucocorticoids. The
      study was conducted on mice sensitized and challenged with ovalbumin and the
      whole body plethysmography was carried out to assess AHR. The bronchoalveolar
      lavage (BAL) histopathology was examined. RESULTS: We found that acetamide-45
      significantly inhibited the enhanced hyperresponsiveness and eosinophil
      recruitment in airways with elimination of cAMP-PDE activity in lung tissue.
      Elevated IL-4 and IL-5 in bronchoalveolar lavage fluid (BALF) in asthmatic mice
      were markedly decreased. CONCLUSION: Our results indicate that the agent has a
      potential role in inflammatory disease.

PMID- 18817625
TI  - Aspergillus fumigatus conidia upregulates NOD2 protein expression both in vitro
      and in vivo.
AB  - AIM: To determine if NOD2 is involved in host recognition of Aspergillus
      fumigatus (Af) conidia. METHODS: An Af conidia pulmonary infection murine model
      was established by intranasal inoculation of Af conidia suspensions. Protein
      levels of NOD2 in lung tissue were determined by immunohistochemistry. A549 and
      phorbol-12-myristate 13-acetate (PMA)-activated THP-1 cell lines were treated
      with heat-killed Af conidia, then the presence of NOD2 protein in these cell
      lines was detected by Western blotting. The ability of muramyl dipeptide (MDP) to
      induce the secretion of TNF-alpha after incubation with heatkilled Af conidia was
      measured by enzyme-linked immunosorbent assay. RESULTS: The expression of NOD2
      protein in lung tissue increased after Af conidia infection. Heat-killed Af
      conidia significantly upregulated NOD2 protein expression in A549 cells and PMA
      activated THP-1 cells. Additionally, Af conidia in conjuction with MDP,
      significantly increased the secretion of TNF-alpha in A549 cells and PMA
      activated THP-1 cells. CONCLUSION: Af conidia upregulates NOD2 protein expression
      in vitro and in vivo. These findings indicate that NOD2 protein may respond to Af
      conidia.

PMID- 18817626
TI  - Ginsenoside Rg1 promotes bone marrow stromal cells proliferation via the
      activation of the estrogen receptor-mediated signaling pathway.
AB  - AIM: To investigate the possible mechanisms of ginsenoside Rg1 promoting bone
      marrow stromal cell (BMSC) proliferation. METHODS: BMSC were isolated from bone
      marrow of Sprague-Dawley rats and maintained in vitro. After stimulation with 1
      micromol/L ginsenoside Rg1 for the indicated time, the proliferation ability of
      BMSC were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium
      bromide and [3H]-thymidine incorporation assays. The estrogen receptor (ER)
      binding activity of BMSC was determined by a specific ER antagonist and an ER
      binding assay. Furthermore, the influence of ginsenoside Rg1 on the expression of
      ERalpha was investigated by RT-PCR and Western blotting assays. RESULTS: BMSC
      proliferation stimulated by 1 micromol/L ginsenoside Rg1 can be completely
      blocked by 1 micromol/L ER antagonist ICI 182, 780, or ERalpha- specific
      antagonist methylpiperidinopyrazole. Moreover, Rg1 failed to displace the
      specific binding of [3H]17beta-estradiol to BMSC cell lysates, suggesting that no
      direct interaction of Rg1 with the ER is needed for its estrogenic effects. In
      addition, 1 micromol/L Rg1 had no effects on the expression of ERalpha in either
      the mRNA or protein levels. CONCLUSION: Our results indicate that ERalpha is
      essential for mediating the effects of Rg1 on stimulating BMSC proliferation,
      which might involve the ligand/receptor-independent activation of ERalpha.

PMID- 18817627
TI  - Effects of RNAi-mediated inhibition of aggrecanase-1 and aggrecanase-2 on rat
      costochondral chondrocytes in vitro.
AB  - AIM: Failure of transplanted cartilage or allogenic chondrocytes is attributed
      mainly to immunological rejection and cartilage degradation. A major feature is
      the loss of aggrecan from the cartilage matrix, primarily due to the action of
      the specific proteinases aggrecanase-1 and aggrecanase-2. The aim of this in
      vitro study was to determine whether the specific inhibition of aggrecanase-1 and
      aggrecanase-2 by RNAi would mitigate aggrecan loss from cultured chondrocytes.
      METHODS: Expression plasmid vectors of shRNA targeting aggrecanase-1 and
      aggrecanase-2 were constructed and transfected into cultured rattus costochondral
      chondrocytes. The transfected cells were induced with interleukin-1beta (IL
      1beta). Gene mRNA levels were analyzed by RT-PCR. Aggrecan and collagen II
      content were measured by immunohistochemistry and Western blotting. RESULTS: As
      the chondrocytes underwent dedifferentiation, aggrecanase-1 increased
      significantly. The specific inhibition of aggrecanase-1 and aggrecanase-2 by RNAi
      had no negative effect on the morphology and growth velocity of the chondrocytes.
      The mRNA of aggrecanase-1 and aggrecanase-2 decreased significantly. The alpha-2
      macroglobulin expression level was increased by the shRNA specific for
      aggrecanase-1. Other genes of the chondrocytic extracellular matrix were not
      affected. RNAi significantly increased the aggrecan and collagen II content of
      chondrocytes treated with IL-1beta. CONCLUSION: The results suggest that
      inhibition of aggrecanase-1 and aggrecanase-2 by RNAi can mitigate aggrecan
      degradation, without interfering with chondrocytic gene phenotype recovery. RNAi
      technology can be a useful tool for studying degenerative processes in cartilage.

PMID- 18817628
TI  - Discovery of sphingosine 1-O-methyltransferase in rat kidney and liver
      homogenates.
AB  - AIM: To characterize sphingosine methyltransferase in rat tissues. METHODS: By
      using S-adenosyl-L-(methyl-3H) methionine, enzymatic activity was measured in the
      rat liver and kidney homogenates. RESULTS: The optimum pH and reaction time for
      the enzyme assay were pH 7.8 and 1 h. ZnCl2 inhibited the activity, but not
      MgCl2, CaCl2, CoCl2, or NiCl2. In the kidney homogenate, enzymatic activity was
      detectable in the cytosol and all membrane fractions from the plasma membrane and
      other organelles; however, in the liver homogenate, enzymatic activity was
      detectable in all membrane fractions, but not in the cytosol. We also tested the
      enzymatic activity with structurally-modified sphingosine derivatives.
      CONCLUSION: We found sphingosine 1-O-methyltransferase activity in the rat liver
      and kidney homogenates.

PMID- 18817629
TI  - Apoptosis induced by diallyl disulfide in human breast cancer cell line MCF-7.
AB  - AIM: To investigate the effect of diallyl disulfide (DADS), a component of
      garlic, on apoptosis in human mammary cancer cell line (MCF-7) and its
      mechanisms. METHODS: Cytotoxicity was analyzed by 3-(4,5-dimethylthiazol-2-yl)
      2,5- diphenyltetrazolium bromide assays. Morphology of apoptotic cells was
      detected by acridine orange and ethidium bromide staining. Apoptotic cells
      stained with propidium iodide were examined using flow cytometry. Protein levels
      were detected by Western blot analysis. RESULTS: DADS inhibited the proliferation
      of MCF-7 cells and induced the apoptotic ratio to increase rapidly. Cleavage of
      the caspase-3 and caspase-3 substrate poly(ADP-ribose) polymerase was observed in
      MCF-7 cells after 24 h of treatment with DADS. When the MCF-7 cells were treated
      with 200 micromol x L DADS, the stress-activated protein kinase extracellular
      signal-regulated kinase (ERK), a mitogen-activated protein kinase, was inhibited
      after 6 h; c-Jun N-terminal kinase (JNK), that is stress-activated protein kinase
      (SAPK), and p38 mitogen-activated protein kinase were activated after 6 h.
      CONCLUSION: These results suggest that DADS both inhibits the proliferation of
      MCF-7 cells and induces apoptosis of MCF-7 cells. The mechanisms may include the
      inhibition of ERK and the activation of the SAPK/JNK and p38 pathways.

PMID- 18817630
TI  - Discrimination analysis of mass spectrometry proteomics for ovarian cancer
      detection.
AB  - AIM: A discrimination analysis has been explored for the probabilistic
      classification of healthy versus ovarian cancer serum samples using proteomics
      data from mass spectrometry (MS). METHODS: The method employs data normalization,
      clustering, and a linear discriminant analysis on surface-enhanced laser
      desorption ionization (SELDI) time-of-flight MS data. The probabilistic
      classification method computes the optimal linear discriminant using the complex
      human blood serum SELDI spectra. Cross-validation and training/testing data-split
      experiments are conducted to verify the optimal discriminant and demonstrate the
      accuracy and robustness of the method. RESULTS: The cluster discrimination method
      achieves excellent performance. The sensitivity, specificity, and positive
      predictive values are above 97% on ovarian cancer. The protein fraction peaks,
      which significantly contribute to the classification, can be available from the
      analysis process. CONCLUSION: The discrimination analysis helps the molecular
      identities of differentially expressed proteins and peptides between the healthy
      and ovarian patients.

PMID- 18817631
TI  - Effects of cyclosporin A and itraconazole on the pharmacokinetics of atorvastatin
      in rats.
AB  - AIM: To evaluate the effects of cyclosporin A and itraconazole, which were used
      as inhibitors of P-glycoprotein (P-gp) and/or cytochrome P450 (CYP) 3A4 on the
      pharmacokinetics of atorvastatin in rats. METHODS: The pharmacokinetic parameters
      of atorvastatin were measured after intravenous (2 mg/kg) and intragastric (10
      mg/kg) administration of atorvastatin in rats, which were pretreated with
      cyclosporin A (5, 10, and 20 mg/kg) or itraconazole (5, 10, and 20 mg/kg).
      RESULTS: Compared with the control rats, cyclosporin A and itraconazole altered
      the pharmacokinetics of atorvastatin significantly. The AUC0-t values of
      atorvastatin after intragastric administration, pretreated with cyclosporin A (5
      20 mg/kg), increased by 32.3%, 61.8%, and 187.2%, respectively, but the CLbile
      values decreased (P<0.01, 5-20 mg/kg). With pretreatment of itraconazole (5-20
      mg/kg), the AUC(0-t) values of atorvastatin increased by 88.2%, 102%, and 123%,
      respectively, but the CL(bile) values decreased (P<0.01, 5-20 mg/kg). CONCLUSION:
      These data indicated that cyclosporin A could be effective in inhibiting the
      efflux of atorvastatin, and itraconazole could be effective in inhibiting both
      the metabolism and biliary excretion of atorvastatin.

PMID- 18817632
TI  - Pharmacokinetics/pharmacodynamics of antofloxacin hydrochloride in a neutropenic
      murine thigh model of Staphylococcus aureus infection.
AB  - AIM: Antofloxacin hydrochloride is a new fluoroquinolone antibiotic with broad
      spectrum in vitro activity. Using the neutropenic murine thigh infection model,
      we defined the pharmacodynamic profile and property of antofloxacin hydrochloride
      against Staphylococcus aureus. METHODS: Single-dose pharmacokinetic studies of
      antofloxacin hydrochloride were carried out in thigh infected mice. Therapy was
      initiated at 2 h postinoculation with 5-640 mg/kg per d fractionated for
      different dosing regimens. The thighs were removed for bacterial measurement
      after 24 h of therapy, the best pharmacokinetic/ pharmacodynamic (PK/PD) index
      correlated with the efficacy was determined by nonlinear regression analysis. A
      sigmoid E(max) dose-response model was used to estimate the daily dose and AUC(24
      h)/MIC (minimal inhibitory concentration) required to achieve a static effect.
      RESULTS: The PK was linear with similar elimination half-life over the dose range
      studied. The AUC(24 h)/MIC ratio was the PK/PD parameter that best correlated
      with efficacy (R(2)=92.3%, 90.8% for the two organisms, compared with C(max)/MIC
      and T>MIC [%], respectively). The 24 h static dose ranged from 34.3 to 153.7
      mg/kg per d for all S aureus strains, the total AUC(24 h)/MIC ratio to achieve
      bacteriostatic effect varied from 31.7 to 122.5 (mean, 65.7+/-30.6). CONCLUSION:
      Antofloxacin hydrochloride showed powerful antibacterial activity against the S
      aureus isolates used in our neutropenic infected mice model. Our data suggested
      that the AUC/MIC ratio appeared to be most closely linked to the bacterial
      outcome (R(2)>90%), and a total AUC(24 h)/MIC ratio of 65.7 appears to be the
      target value to achieve a net bactericidal activity against S aureus, similar to
      the results of other fluoroquinolones.

PMID- 18817633
TI  - Symmetrical 1-pyrrolidineacetamide showing anti-HIV activity through a new
      binding site on HIV-1 integrase.
AB  - AIM: To characterize the functional and pharmacological features of a symmetrical
      1-pyrrolidineacetamide, N,N'-(methylene-di-4,1-phenylene) bis-1
      pyrrolidineacetamide, as a new anti-HIV compound which could competitively
      inhibit HIV-1 integrase (IN) binding to viral DNA. METHODS: A surface plasma
      resonance (SPR)-based competitive assay was employed to determine the compound's
      inhibitory activity, and the 3-(4,5-dimethylthiazol- 2-yl)-2,5
      diphenyltetrazolium bromide cell assay was used to qualify the antiviral
      activity. The potential binding sites were predicted by molecular modeling and
      determined by site-directed mutagenesis and a SPR binding assay. RESULTS: 1
      pyrrolidineacetamide, N,N'-(methylene-di-4,1-phenylene) bis-1
      pyrrolidineacetamide could competitively inhibit IN binding to viral DNA with a
      50% inhibitory concentration (IC(50)) value of 7.29+/-0.68 micromol/L as
      investigated by SPR-based investigation. Another antiretroviral activity assay
      showed that this compound exhibited inhibition against HIV-1(IIIB) replication
      with a 50% effective concentration (EC(50)) value of 40.54 micromol/L in C8166
      cells, and cytotoxicity with a cytotoxic concentration value of 173.84 micromol/L
      in mock-infected C8166 cells. Molecular docking predicted 3 potential residues as
      1-pyrrolidineacetamide, N,N'-(methylene-di-4,1-phenylene)bis-1-
      pyrrolidineacetamide binding sites. The importance of 3 key amino acid residues
      (Lys103, Lys173, and Thr174) involved in the binding was further identified by
      site-directed mutagenesis and a SPR binding assay. CONCLUSION: This present work
      identified a new anti-HIV compound through a new IN-binding site which is
      expected to supply new potential drug-binding site information for HIV-1
      integrase inhibitor discovery and development.

PMID- 18817634
TI  - Discovery and characterization of a novel inhibitor of CDC25B, LGH00045.
AB  - AIM: Cell division cycle 25 (CDC25) phosphatases have recently been considered as
      potential targets for the development of new cancer therapeutic agents. We aimed
      to discover novel CDC25B inhibitors in the present study. METHODS: A molecular
      level high-throughput screening (HTS) assay was set up to screen a set of 48000
      pure compounds. RESULTS: HTS, whose average Z' factor is 0.55, was finished and
      LGH00045, a mixed-type CDC25B inhibitor with a novel structure and relative
      selectivity for protein tyrosine phosphatases, was identified. Furthermore,
      LGH00045 impaired the proliferation of tumor cells and increased cyclin-dependent
      kinase 1 inhibitory tyrosine phosphorylation. In synchronized HeLa cells,
      LGH00045 delayed cell cycle progression at the G2-M transition. CONCLUSION:
      LGH00045, a novel CDC25B inhibitor identified through HTS, showed good inhibition
      on the proliferation of tumor cells and affected the cell cycle progression,
      which makes it a good hit for further structure modification.

PMID- 18817635
TI  - The role of high-mobility group box 1 protein in the pathogenesis of autoimmune
      diseases.

PMID- 18817637
TI  - Behcet's disease: recent advances in early diagnosis and effective treatment.
AB  - Behcet's disease (BD) is a chronic, multisystem, inflammatory disorder that is
      classified among the systemic vasculitidies. Its cause has yet to be determined,
      but genetic and environmental factors and immune dysregulation are thought to
      play a role in its pathogenesis. The diagnosis of the disease and recognition and
      separation from disorders that may mimic BD may be difficult, especially in areas
      where the disease is uncommon. Certainty as to the best treatments for the
      various manifestations of BD is often unclear due to limited randomized
      controlled trials. However, existing consensus statements and expert opinions
      should help to guide therapy. This review examines important recent contributions
      to help the clinician more readily recognize patients with the disease and
      institute appropriate care.

PMID- 18817638
TI  - Spondyloarthritis at the crossroads of imaging, pathology, and structural damage
      in the era of biologics.
AB  - Ankylosing spondylitis (AS) is characterized by two key pathologic findings:
      sacroiliac joint and spinal inflammation and new bone formation with possible
      bone fusion, usually in the axial skeleton. Thus, structural damage in AS must be
      viewed differently than that in rheumatoid arthritis. Tumor necrosis factor
      blockers effectively inhibit inflammation, as shown by signs and symptoms,
      function, C-reactive protein, and MRI, and will probably prevent erosive
      structural damage. However, the ossification of already-damaged bone cannot be
      influenced by tumor necrosis factor blockade, because these drugs do not inhibit
      osteoblasts. It remains to be seen whether additional targeting of new bone
      formation is clinically meaningful in advanced AS. The most important action to
      prevent structural damage is probably an early diagnosis and effective anti
      inflammatory treatment of AS.

PMID- 18817639
TI  - Do bisphosphonates and statins have a role in spondyloarthritis management?
AB  - Bisphosphonates and statins target the mevalonate pathway of biosynthesis of
      prenyl groups, which are necessary for the lipid modification of small GTP
      binding proteins (eg, Ras, Rac, Rho) that transduce a wide array of extracellular
      growth and differentiation signals from cell surface receptors to the nucleus.
      Interference with this pathway has been shown to confer beneficial anti
      inflammatory properties in vitro and in animal models of inflammation. Primarily
      open-label data in spondylo-arthritis suggests mild to moderate efficacy on
      symptoms and function but their primary clinical role may be as adjunctive
      therapy to manage systemic osteoporosis and risk for cardiovascular events.

PMID- 18817640
TI  - Are spondyloarthropathies as common as rheumatoid arthritis worldwide? A review.
AB  - The high-range estimate of 1.3% by the National Arthritis Data Workgroup for the
      prevalence of the entire spectrum of spondyloarthropathies (SpAs) suggests that
      SpAs may be more prevalent than rheumatoid arthritis (RA) in the United States.
      Recent surveys from many European countries using the same sample population have
      also found SpA to be at least as common as RA in most of the studied populations,
      including Finnish, Swedish, Lithuanian, French, Italian, and Turkish. Among Asian
      populations, China has the highest prevalence of SpA, with reported estimates
      generally higher than that of RA. In Thailand and Vietnam, the two diseases are
      probably equally common, whereas RA seems to be more prevalent than SpA in the
      rest of Asia, the Pacific Region, and Latin America, as indicated by studies
      following the COPCORD (Community-Oriented Program for the Control of Rheumatic
      Diseases) protocol. Both rheumatic disorders are rare in Africa, but SpA is less
      common than RA.

PMID- 18817643
TI  - Tumor necrosis factor inhibitors and infection complications.
AB  - Rheumatoid arthritis patients are at heightened risk for infections because of
      intrinsic disease severity with associated inflammation, comorbid illnesses, and
      use of glucocorticoids and various immunosuppressives. Although several studies
      have reported up to a twofold increase in risk of serious infections in RA
      patients treated with anti-tumor necrosis factor-alpha agents, results from other
      studies have been conflicting. Comparing results from different studies is
      challenging because of differences in patient populations, heterogeneous
      prevalence of comorbidities, and differing patterns of concomitant medication
      use. Based on available evidence, an excess risk for infection occurs early after
      initiation of tumor necrosis factor-alpha inhibitor therapy. Additionally,
      special circumstances such as surgical procedures may increase infection risk.
      The appropriate use of biologics in the perioperative setting remains empiric at
      best.

PMID- 18817644
TI  - Rheumatoid arthritis and cardiovascular disease.
AB  - An increased risk of cardiovascular events and subclinical atherosclerosis in
      patients with rheumatoid arthritis (RA) has been attributed to the inflammatory
      milieu associated with this chronic autoimmune disease and possibly to the
      independent effects of RA medications on risk. This review provides an update on
      the most recent epidemiologic studies documenting this relationship and
      noteworthy publications examining RA-related factors that could influence the
      role of traditional cardiovascular risk factors and expression of atherosclerotic
      disease in patients with RA.

PMID- 18817645
TI  - Current status of gene therapy for rheumatoid arthritis.
AB  - Gene therapy offers great possibilities for treating rheumatoid arthritis (RA).
      Traditional surgical and pharmaceutical methods of treating RA have met with
      limited therapeutic success and have failed to produce a cure, but the past
      several years have seen extensive progress toward development of a gene therapy
      for arthritis. Numerous vectors and therapeutic genes have been investigated in
      animal models of arthritis, and the potential of gene therapy to treat or manage
      RA has been demonstrated in several clinical studies. Gene therapy offers the
      possibility of overcoming many of the limitations of current biologic therapies
      by providing long-term, high-level localized expression of therapeutic genes,
      potentially in as little as a single dose. In this review, we explore the
      advances in gene therapy for RA and summarize the recent preclinical and clinical
      data. In addition, we provide an overview of vectors and targets for RA gene
      therapy.

PMID- 18817646
TI  - Regulatory T cells in rheumatoid arthritis.
AB  - Regulatory T cells have attracted substantial interest in connection with their
      role in controlling autoimmunity and the possibility that they could be used
      therapeutically. Here, we summarize the current understanding of the several
      subsets of regulatory T cells and defects in their function in rheumatoid
      arthritis. In evaluating the possibility of using regulatory T cells to treat
      rheumatoid arthritis, the relationship between these cells and the development
      and function of Th17 cells must be understood fully.

PMID- 18817647
TI  - Inhibiting interleukin-6 in rheumatoid arthritis.
AB  - Interleukin (IL)-6 is the most abundant proinflammatory cytokine in the
      circulation and synovial joints of patients with active rheumatoid arthritis. It
      has pivotal roles in the immune response and inflammation. In rheumatoid
      arthritis, it causes synovitis, joint destruction, and many systemic
      manifestations. Clinical trials of tocilizumab, a humanized anti-IL-6 receptor
      monoclonal antibody that blocks IL-6 signaling, have demonstrated therapeutic
      benefit. It heralds a new era of anticytokine therapy in rheumatoid arthritis.

PMID- 18817648
TI  - [The influence of correct blood pressure measurement on the diagnostic decisions
      in hypertensive patients. MEDIDA study].
AB  - BACKGROUND AND OBJECTIVE: We aimed to assess the influence of correct blood
      pressure (BP) measurement, following the recommendations of the Spanish Guideline
      of Hypertension 2005 (SGH), on the diagnostic decisions in hypertensive patients.
      PATIENTS AND METHOD: Prospective, longitudinal, observational, multicenter study
      conducted in hypertensive patients with stable pharmacologic therapy in primary
      care units. 4040 patients were included, in whom BP was measured following
      current clinical practice at the first visit (visit 1). After 7 days no
      therapeutic changes could be made and BP was measured following the criteria of
      good BP measurement from the SGH (visit 2). Control rate was assessed both,
      following the investigators opinion and the SGH algorithm, at visits 1 and 2.
      Differences in therapeutic recommendations between visits were assessed. RESULTS:
      3436 patients were evaluable (48.9% women), with mean age (standard deviation) of
      63.4 (11.4) years. Decreases in systolic/diastolic BP of 4.8 mmHg (95% confidence
      interval [CI], 4.5-5.1) and 2.8 mmHg (95% CI, 2.6-3.0) between visits were
      observed. The control rate following the investigators opinion was of 59.1% (95%
      CI, 57.4-60.8%) at visit 1 and 76.4% (95% CI, 75.0-77.9%) at visit 2, and the one
      following the criteria of the SGH was 32.2% (95% CI, 30.6-33.7%) at visit 1 and
      46.6% (95% CI, 44.9-48.3%) at visit 2. The rate of patients in which therapeutic
      recommendations were changed was of 54.1% (95% CI, 52.4-55.7%). CONCLUSIONS:
      Applying the recommendations of the SHG for correct BP measurement led to
      increased control rate in relation to a previous measurement, prompting changes
      in the therapeutic attitude.

PMID- 18817650
TI  - [Clinical usefulness of biochemical markers of bone turnover in early
      postmenopausal women: two years longitudinal study].
AB  - BACKGROUND AND OBJECTIVE: Many studies have been performed on the ability of bone
      turnover markers (BTM) for the prediction of bone loss and to assess the
      correlation of BTM with bone mineral density (BMD). However, the results from
      these studies have been mixed. The aim of this study was to assess the usefulness
      of BTM to predict bone loss and to analize the correlation of BTM with BMD in
      early postmenopausal women. SUBJECTS AND METHOD: 183 healthy women, aged 50 to 55
      years, with natural menopause of 6 to 36 months were randomly selected. We
      measured bone alkaline phosphatase (BALP), intact osteocalcine (OC) and C
      telopeptide (sCTx) in serum, and calcium, deoxipiridinoline (DPD) and N
      telopeptide (NTx) in urine. Bone densitometry of the spine (L(2)-L(4)) was
      performed at the start of the study and two years later. Student t test, ANOVA,
      chi2 test and ROC curves were used for the statistical analysis. RESULTS: Bone
      markers, mainly OC and CTx, correlated with BMD and discriminated osteoporosis,
      osteopenia and normal bone mass (p < 0.001). According to the ROC curves, OC had
      a sensitivity of 77.8% and specificity of 80.6% for the diagnosis of osteoporosis
      and sCTx, 83.3% and 74.5%, respectively. Regarding the relation to bone loss,
      only sCTx showed difference between the lowest and the highest quartile (p =
      0.042), but we did not find an association between high turnover and fast bone
      losers. CONCLUSIONS: Bone markers, mainly OC and sCTx, are useful for
      identification of osteoporotic and osteopenic early postmenopausal women.
      However, regarding the bone loss, only CTx has a weak predictive value.

PMID- 18817649
TI  - [Assessment of the simplified versions of the Asthma Control Questionnaire].
AB  - BACKGROUND AND OBJECTIVE: The aim of this study was to assess the measurement
      properties of the Spanish version of Asthma Control Questionnaire (ACQ) when FEV1
      item in the original version (ACQ-FEV1) is substituted by peak expiratory flow
      rate (ACQ-PEF) and when the lung function item is omitted (ACQ-wLF). MATERIAL AND
      METHOD: and 607 patients were enrolled in this study. Three study visits were
      carried out: at baseline, 2, and 6 weeks later. Validity, reliability and
      sensitivity to change of both ACQ versions were calculated. RESULTS: ACQ-PEF and
      ACQ-wLF had a correlation coefficient of 0.38 and 0.39 with no exacerbations.
      Both symptoms improvement and a better perception of asthma control, both by
      physicians and patients, were significantly related ro better scores in both
      versions (P <0.01). Cronbach a of ACQ-PEF and ACQ-wLF were 0.83 and 0.87,
      respectively. Intraclass correlation coefficients of both ACQ-PEF and ACQ-wLF
      were 0.9 and 0.87. Mean scores of all ACQ versions (ACQ-FEV1, ACQ-PEF and ACQ
      wLF) were 1.31 (1), 1.34 (1) and 1.14 (1.1), respectively, being all differences
      statistically significant P < or = 0.003). CONCLUSIONS: Replacement of FEV1 by
      PEF, or its elimination, does not alter the measurement properties of the ACQ
      questionnaire. Use of ACQ simplified versions is recommended only for
      investigational purposes, without combining in the same analysis scores obtained
      with different versions of the questionnaire.

PMID- 18817651
TI  - [Blood pressure measurement and control of hypertension].

PMID- 18817652
TI  - [Emulating scientific publication].

PMID- 18817653
TI  - [Post-streptococcal uveitis].

PMID- 18817654
TI  - [Acute renal failure in a 64-year-old patient with chronic hepatitis].

PMID- 18817655
TI  - [Secular trend of menarcheal age in Spanish adolescents].

PMID- 18817656
TI  - [Trimethylaminuria (fish-odor syndrome): a case report].

PMID- 18817657
TI  - [Chronic lymphocytic leukemia concurrent with myeloid/natural killer cell
      precursor acute leukemia diagnosis].

PMID- 18817658
TI  - [Upper gastrointestinal bleeding associated with clopidogrel and paroxetine].

PMID- 18817659
TI  - [Turner's syndrome with precocious puberty].

PMID- 18817660
TI  - [Dermatobia homini myiasis acquired during a travel to Argentina].

PMID- 18817661
TI  - [Scabies].

PMID- 18817662
TI  - Diagnostic approach in suspected recurrent primary brain tumors using (18)FDG
      PET/MRI, perfusion MRI, visual and quantitative analysis, and three dimensional
      stereotactic surface projections. First experience in Mexico.
AB  - Thirty patients with primary cerebral tumors WHO III and IV previously treated,
      undergoing evaluation for tumoral recurrence, they underwent (18)FDG-PET study,
      MRI and PMRI. PET uptake was determined by visual inspection and was quantified
      by use of standard uptake values, the ratio of tumor uptake to normal tissue and
      were z scored using automated voxel-based comparison. PMRI was quantified by use
      of ratios of cerebral blood volume (rCBV). The accuracies were determined by
      comparing imaging data with histologic findings and clinical follow up of up to
      21 mo. RESULTS: Sensitivity (Se), specificity (Sp), positive predictive value
      (PPV), negative predictive value (NPV) and accuracy were 100 %, 82 %, 90 %, 100 %
      and 93 % respectively for the PET/MRI fusion and 68 %, 82 %, 87 %, 60 % and 73 %
      respectively for PMRI. There were two false positive cases for PET/MRI fusion
      that were confirmed by biopsy: chronic inflammation; and foreign body granulomas.
      The receiver operating characteristic (ROC) curve analysis showed statistically
      significant difference (p = 0.0225). CONCLUSIONS: (18)FDG SUVs, glucose uptake
      ratios and 3D stereotactic surface projections in brain tumors were not a
      reliable measure for evaluating recurrent tumors. PET/MRI fusion was more
      sensitive and accurate than PMRI for imaging recurrent primary brain tumors. The
      region of interest can be visually analyzed on the PET/MRI fusion images and
      described as recurrent tumor when any activity (lower, equal or greater than the
      contralateral cortex) is presented in the zone of hyperintensity seen on the post
      gadolinium T1-weighted MRI.

PMID- 18817663
TI  - [Usefulness of ventricular function values obtained using post-stress gated-SPECT
      in a diabetic population with clinical suspicion of ischaemic heart disease].
AB  - OBJECTIVE: To assess the clinical usefulness of left ventricular function values
      obtained using post-stress myocardial perfusion gated-SPECT in diabetic patients
      with suspected ischaemic heart disease (IHD). MATERIALS AND METHODS: Sixty-one
      patients with diabetes mellitus (DM), with clinical suspicion of IHD and no
      previous history of heart disease were studied. Ergometric or pharmacological
      post-stress myocardial perfusion gated-SPECT was performed on all patients. The
      relationship between the ejection fraction values and ventricular volumes, and
      the perfusion study results, final diagnosis, severity of the perfusion defects
      and the clinical evolution was studied. The mean follow-up time was 14 months.
      RESULTS; All the ventricular function values independently showed significant
      differences between the groups with a normal and pathological perfusion study,
      and between groups with a final diagnosis of IHD and non-IHD. After multivariate
      logistic regression, the end-diastolic volume (EDV) was the only value which
      showed a statistical association with the pathological perfusion study, its
      severity and the final diagnosis of IHD. No statistical association was observed
      between the ventricular function values and the occurrence of cardiac events.
      CONCLUSIONS: All the ventricular function values obtained by gated-SPECT added
      diagnostic information to the post-stress myocardial perfusion study in the
      diabetic population with suspected IHD; however, only EDV showed a statistical
      association with the pathological perfusion study, severity of defects and the
      final diagnosis of IHD.

PMID- 18817664
TI  - [Assessment of cerebral blood flow in patients with eating disorders in the acute
      clinical phase using Tc99m-HMPAO spect].
AB  - OBJECTIVE: To assess the status of cerebral perfusion in patients with eating
      disorders (ED) in the acute phase of the disease. MATERIALS AND METHODS:
      Seventeen patients, with a mean age of 22 years, diagnosed with ED according to
      DSM-III-R (Diagnostic and Statistical Manual of Mental Disorders) criteria and
      under close clinical monitoring were studied in the initial acute phase of their
      disease. Brain SPECT with 15 mCi of Tc99m HMPAO was performed on all patients and
      assessed using visual and semi-quantitative analysis. The latter was carried out
      by obtaining left/right indices in sixteen symmetrical 5 x 5 pixel regions of
      interest (ROI) in three transverse slices, one below the cantho-meatal line and
      two above, at 2 and 5 cm, respectively. RESULTS; Visual analysis showed
      hypoperfusion of the anteroinferior region of the left temporal lobe in 7/17
      patients, and in the homonymous region of the right temporal lobe in 1/17. Semi
      quantitative analysis did not show statistically significant differences in the
      slices above the cantho-meatal line when the means of the asymmetry indices were
      compared between the anterior (frontal), middle (temporal and parietal) and
      posterior (occipital) regions of each slice, obtaining values ranging between
      0.99 +/- 0.05 and 1.02 +/- 0.03. However, in the lowest slice, the anterior
      (temporal) region showed a mean asymmetry value of 0.89 +/- 0.15, and on
      comparing it with the mean of the asymmetry indices of the posterior region
      (cerebellum), it showed a statistically significant difference (p < 0.05).
      CONCLUSION: Patients with ED frequently show hypoperfusion of the anteroinferior
      region of the temporal lobe, predominantly in the left hemisphere, in the acute
      phase of the illness.

PMID- 18817665
TI  - Focal myocardial uptake in a patient with carcinoid tumor by indium-111
      pentetreotide on SPECT/CT.
AB  - We present a case of a 44 year old man with flushing, diarrhea and markedly
      elevated 24 hour urinary 5-HIAA level, who was referred for an indium-111
      pentetreotide study, after the excision of a carcinoid tumor in the terminal
      ileum. Scan findings revealed focal uptake in the myocardium and liver,
      suspicious for metastases. Subsequent transthoracic echocardiogram failed to
      demonstrate a cardiac lesion. Previously, our group has unequivocally
      demonstrated the usefulness of software fusion of SPECT and CT imaging in the
      evaluation of a carcinoid metastasizing to the myocardium. This case illustrates
      that hardware SPECT/CT fusion imaging utilizing indium-111 pentetreotide to
      evaluate metastatic carcinoid tumors can be useful. In addition, the
      echocardiogram can yield false negative results, because of a smaller lesion size
      and the influence of an operator-dependent factor.

PMID- 18817666
TI  - [Circumscript myositis ossificans in a four-year-old boy].
AB  - We present the case of a 4 year old boy with no previous personal or family
      history of interest, who attended the Paediatric Department of our hospital after
      a physical examination revealed a painful induration in the left arm which had
      increased in size; imaging tests were consistent with a calcified mass in soft
      tissues, without cortical involvement, suspected of being malignant. Two-phase
      bone scintigraphy was requested in which a soft tissue lesion, not suggestive of
      malignancy, was detected. The biopsy was negative for malignant cells. However,
      in view of the progressive increase in size of the lesion, FDG positron emission
      tomography (FDG-PET) was performed, showing a hypermetabolic mass consistent with
      malignancy in the left arm, for which the patient underwent surgery for suspected
      possible parosteal osteosarcoma.

PMID- 18817667
TI  - [The role of bone scintigraphy in two cases of hereditary multiple exostoses].
AB  - We present the cases of two patients aged 18 and 40 years, with no previous
      personal history of interest. The only symptoms reported by the first patient in
      the previous year were episodes of pain and stiffness without inflammation in the
      right knee and third finger of the right hand. These episodes lasted two to three
      weeks. Our second patient presented numbness in the lower left limb over the
      previous year. The analytical study was normal. The patients were diagnosed with
      hereditary multiple exostoses, based on the clinical, radiological and
      scintigraphic findings. The bone scintigraphy enabled whole body images to be
      obtained in a single examination and may be used for the differential diagnosis
      of other osteoarticular conditions, as well as for the follow-up and assessment
      of the response to treatment.

PMID- 18817668
TI  - Liver and vertebral visualization on lung perfusion scan.

PMID- 18817669
TI  - [Metachronous suprarenal metastasis of non-microcytic lung cancer in a patient
      with bilateral adrenal adenomas].

PMID- 18817670
TI  - [Evolution of brain scintigraphy with Tc-99m ECD in brain death].

PMID- 18817671
TI  - [Evaluation of ventricular function in Nuclear Medicine].

PMID- 18817672
TI  - [... and the surgeons of our hospitals: Are they blind?].

PMID- 18817673
TI  - [Valencia 2008: The initiative of the electronic poster].

PMID- 18817674
TI  - Evaluation of vessel response to percutaneous coronary intervention.

PMID- 18817675
TI  - In-hospital mortality in stroke patients.

PMID- 18817676
TI  - Prevalence of heart failure: a reflection of the good and the bad of modern
      cardiovascular care.

PMID- 18817677
TI  - Characterization of edge effects with paclitaxel-eluting stents using serial
      intravascular ultrasound radiofrequency data analysis: the BETAX (BEside TAXus)
      Study.
AB  - INTRODUCTION AND OBJECTIVES: At present, the effect of paclitaxel on tissue
      structure at the edges of Taxus(R) stents is unknown. The objective of this study
      was to investigate in vivo the temporal changes occurring at the edges of
      paclitaxel-eluting stents using intravascular ultrasound radiofrequency (IVUS-RF)
      data analysis. METHODS: The study included 24 patients who had a total of 26
      paclitaxel-eluting stented segments. In all patients, IVUS-RF imaging was
      performed 5 mm proximally and 5 mm distally to the stent edges 6 months after
      stent implantation. For subsequent analysis, proximal and distal segments were
      divided into five 1-mm subsegments. RESULTS: In the first two subsegments
      adjacent to the proximal edge of the stent, the vessel wall had grown to
      compensate for plaque growth without affecting the vessel lumen, while in the
      remaining three subsegments there was overcompensation (i.e., the vessel wall
      increased to greater than the plaque size). Consequently, the lumen had increased
      in size. At the distal edge of the stent, overcompensation was observed in all
      five subsegments and the lumen had increased in size. In general, proximal and
      distal growth was due to an increase in fibrolipid plaque (P< .001 and P< .001,
      respectively) along with a decrease in the necrotic core (P=.014 and P< .001,
      respectively) and the presence of dense calcium (P< .001 and P< .001,
      respectively). CONCLUSIONS: Serial expansive vascular remodeling was observed at
      proximal and distal stent edges. Remodeling occurred in response to tissue
      growth, which was mainly due to increased fibrofatty tissue.

PMID- 18817678
TI  - Importance of cardiovascular risk profile for in-hospital mortality due to
      cerebral infarction.
AB  - INTRODUCTION AND OBJECTIVES: To investigate cardiovascular risk profiles and
      their prognostic implications in patients with different subtypes of cerebral
      infarction. METHODS: The study involved the retrospective analysis of data from a
      hospital stroke registry on 2704 consecutive CI patients who were admitted
      between 1986 and 2004. Of the 2704 strokes recorded, 770 were classified as
      thrombotic, 763 as cardioembolic, 733 as lacunar, 324 as undetermined and 114 as
      atypical. Multivariate analysis was used to compare cardiovascular risk profiles
      in each subtype and their influence on inhospital mortality. RESULTS: Arterial
      hypertension (AH) was present in 55.5%, atrial fibrillation (AF) in 29.8%, and
      diabetes mellitus in 23.4%. The in-hospital mortality rate was 12.9%, and in
      hospital mortality was independently associated with AF (odds ratio [OR]=2.33;
      95% confidence interval [CI], 1.84-2.96), and heart failure (HF) (OR=1.96; 95%
      CI, 1.33-2.89). In patients with thrombotic stroke, the cardiovascular risk
      factors associated with in-hospital mortality were HF (OR=2.87; 95% CI, 1.45
      5.71), AF (OR=1.80; 95% CI, 1.09-2.96) and age (OR=1.06; 95% CI, 1.04-1.08). In
      patients with cardioembolic stroke, they were peripheral vascular disease
      (OR=2.18; 95% CI, 1.17-4.05), previous cerebral infarction (OR=1.75; 95% CI, 1.16
      2.63), HF (OR=1.71; 95% CI, 1.01-2.90), and age (OR=1.06; 95% CI, 1.04-1.08). In
      those with undetermined stroke, they were AH (OR=3.68; 95% CI, 1.78-7.62) and age
      (OR=1.05; 95% CI, 1.01-1.09). CONCLUSIONS: Each cerebral infarction etiologic
      subtype was associated with its own cardiovascular risk profile. Consequently,
      the cardiovascular risk factors associated with mortality were also different for
      each ischemic stroke subtype.

PMID- 18817679
TI  - Prevalence, geographic distribution and geographic variability of major
      cardiovascular risk factors in Spain. Pooled analysis of data from population
      based epidemiological studies: the ERICE Study.
AB  - INTRODUCTION AND OBJECTIVES: To determine the prevalence and geographic
      distribution of major cardiovascular risk factors in the Spanish population. To
      investigate whether geographic variability exists. METHODS: Data were pooled from
      eight cross-sectional epidemiologic studies carried out in Spain between 1992 and
      2001 whose methodological quality satisfied predefined criteria. Individual data
      were reassessed and analyzed by age group (20-44 years, 45-64 years, and 365
      years), sex and geographic area. The study population included 19,729
      individuals. Mean values and unadjusted and adjusted prevalence rates were
      derived for various risk factors. RESULTS: The most common cardiovascular risk
      factors in the Spanish population were, in descending order: hypercholesterolemia
      (i.e., total cholesterol >200 mg/dL) in 46.7%, hypertension in 37.6%, smoking in
      32.2%, obesity in 22.8%, and diabetes mellitus in 6.2%. The mean values for blood
      pressure, body mass index, high-density lipoprotein cholesterol and glycemia
      varied considerably with age, sex and geographic area. The highest levels of
      cardiovascular risk factors were observed in Mediterranean and south-eastern
      areas of the country and the lowest, in northern and central areas. CONCLUSIONS:
      The prevalence of major cardiovascular risk factors in Spain was high. Their
      distribution varied considerably with geographic area.

PMID- 18817681
TI  - Predictors of mortality and reoperation in acute type-a aortic dissection
      surgery: 18 years of experience.
AB  - INTRODUCTION AND OBJECTIVES: To describe our experience with acute type-A aortic
      dissection surgery, including an analysis of the effect of cerebral protection on
      outcome. METHODS: Between March 1990 and October 2007, 98 consecutive patients
      underwent surgery for acute type-A aortic dissection. Of these, 85 had an
      ascending aorta replacement, while the entire arch was replaced in 13. The aortic
      valve was replaced in 34 patients but preserved in the rest. An intimal tear was
      observed in 83 patients. RESULTS: The in-hospital mortality rate was 15%. Risk
      factors for in-hospital mortality were age > or = 70 years and preoperative
      cardiogenic shock (P< .05). Antegrade cerebral perfusion was used in the last 16
      consecutive patients, whose in-hospital mortality rate was 6%. The proportions of
      patients who survived and who did not require reoperation at 1, 5 and 10 years of
      follow-up were 98.6%+/-1.3%, 86.2%+/-4.6% and 68.2%+/-8.9%, and 97.2%+/-1.9%,
      82.5%+/-4.8% and 55.9%+/-7.9% for the two outcomes, respectively. The risk
      factors for reoperation were found to be severe preoperative aortic regurgitation
      and preservation of the aortic valve (P< .05). The only risk factor for late
      mortality was not using antegrade cerebral perfusion (P< .05). CONCLUSIONS:
      Despite its seriousness, surgery for acute aortic dissection produces good early
      and long-term results. Antegrade cerebral perfusion improves the prognosis of
      these patients and should be the technique of choice for cerebral protection.

PMID- 18817682
TI  - Low-dose dobutamine gated-SPECT analysis of left ventricular segmental wall
      thickening in ischemic cardiomyopathy.
AB  - INTRODUCTION AND OBJECTIVES: The objective of this study was to use low-dose
      dobutamine (LDD) gated single-photon emission computed tomography (SPECT) to
      evaluate segmental thickening of the left ventricle (LV) and its relationship
      with changes in ejection fraction (EF) and ventricular volumes in patients with
      ischemic cardiomyopathy. METHODS: This prospective multicenter study involved 89
      patients with ischemic cardiomyopathy (i.e., EF < or =40%) who underwent LDD
      gated-SPECT at rest. The LV was divided into 17 segments and systolic thickening
      was assessed in a total of 1513 segments during LDD infusion. RESULTS; A
      significant increase in LVEF (33.2% vs. 30.8%; P< .001) was observed during LDD
      infusion and occurred at the expense of a reduction in end-systolic volume (130.5
      mL vs. 136.4 mL; P=.005). The increase in EF was > or =5% in 33.7% of patients,
      while the EF decreased by > or =5% in 5.6% of patients. With LDD infusion, both
      an improvement in > or =3 segments with severely decreased baseline thickening
      (odds ratio [OR] = 18.3; 95% confidence interval [CI], 5.3-63) and an improvement
      in > or =10 segments with mild-to-moderate alterations in baseline thickening (OR
      = 4.53; 95% CI, 1.26-16.16) were associated with a > or =5% increase in LVEF.
      CONCLUSIONS: During the assessment of global left ventricular contractile reserve
      by LDD gated-SPECT, attention should be paid not only to the behavior of segments
      with severely decreased baseline thickening, which are generally regarded as
      indicating viability, but also to segments with mild-to-moderate alterations and
      to those in which thickening decreases.

PMID- 18817683
TI  - Stent-graft repair in acute and chronic diseases of the thoracic aorta.
AB  - Thoracic aortic endografting has demonstrated encouraging mid-term results and
      attracts growing acceptance as a valuable treatment option for chronic aneurysmal
      disease. The emerging role of endovascular strategies for management of acute
      thoracic aortic pathologies is even more exciting considering the sobering
      results of open repair. Although it is accepted that patients at high risk for
      open surgery will benefit from endovascular strategies, the exact role of stent
      graft interventions remains to be defined as the medical community awaits solid
      long-term data and better devices. While some indications and scenarios such as
      acute type B dissection with associated malperfusion syndrome or imminent aortic
      rupture have shown to benefit from stent-graft treatment, other scenarios are
      less settled. The current paper discusses both the established and emerging
      indications, as well as technical and anatomical aspects of this fascinating
      therapeutic option.

PMID- 18817680
TI  - Prevalence of heart failure in the Spanish general population aged over 45 years.
      The PRICE Study.
AB  - INTRODUCTION AND OBJECTIVES: Congestive heart failure is associated with
      substantial morbidity and mortality and both its incidence and prevalence are
      high. Nevertheless, comprehensive data on this condition in Spain are lacking.
      The aim of this study was to determine the prevalence of congestive heart failure
      in Spain. METHODS: A demographic study which involved the participation of 15
      healthcare centers throughout Spain was carried out. In each health area, a
      random sample was taken of the population aged 45 years or more. These
      individuals were examined by their primary care physicians, who made their
      diagnoses using Framingham criteria. Individuals who satisfied criteria for
      congestive heart failure were referred to a cardiologist for confirmation of the
      diagnosis and for echocardiography. RESULTS: Overall, 1776 individuals were
      evaluated. Their mean age was 64+/-12 years (range, 45-100 years) and 44% were
      male. Of these, 242 were referred to a cardiologist. The weighted prevalence of
      congestive heart failure was 6.8% (95% confidence interval [CI] 4%-8.7%). The
      prevalence was similar in men (6.5%, 95% CI 4.7%-8.4%) and women (7%, 95% CI 4.4%
      9.6%). When analyzed by age, the prevalence was 1.3% (0.4%-2.1%) in those aged 45
      54 years, 5.5% (2.4%-8.5%) in those aged 55-64 years, 8% (4.2%-11.8%) in those
      aged 65-74 years, and 16.1% (11%-21.1%) in those aged over 74 years. CONCLUSIONS:
      Prevalence of congestive heart failure in Spain is high, at about 7%-8%. The
      prevalence was similar in males and females, and appeared to increase with age.

PMID- 18817684
TI  - Reducing cardioverter-defibrillator shock administration by antitachycardia
      pacing during device charging.

PMID- 18817685
TI  - Cardiac resynchronization therapy and valvular cardiomyopathy after corrective
      surgery.
AB  - Cardiac resynchronization therapy (CRT) has been shown to have clinical benefits
      in certain groups of patients with advanced heart failure (HF). However, patients
      with valvular cardiomyopathy are underrepresented in randomized clinical studies.
      The aim of this study was to assess the medium-term (i.e., at 6 months) effects
      of CRT in patients with HF exclusively due to valvular disease. The study
      included 40 consecutive patients who underwent CRT device implantation. At 6
      months, there were improvements in functional class, left ventricular remodeling,
      and intraventricular dyssynchrony parameters in treated patients. In this
      particular subgroup of patients, the benefits of CRT were similar to those
      observed in patients with HF due to other etiologies.

PMID- 18817686
TI  - Ventricular arrhythmia onset during diagnostic coronary angiography with a 5F or
      4F universal catheter.
AB  - Of 18,365 patients who underwent coronary angiography with a 4F or 5F universal
      catheter between April 2004 and May 2007, 24 (0.131%) experienced sustained
      ventricular tachycardia or ventricular fibrillation during the procedure. There
      was no significant difference in any clinical or angiographic characteristic
      between patients who had a ventricular arrhythmia and those who did not. Of the
      24 episodes of ventricular arrhythmia, 14 were related to catheter manipulation,
      8 to ischemia, and 2 to the contrast medium, while the cause could not be clearly
      established in 4. The incidence of ventricular arrhythmia with a universal
      catheter was 0.131%, and with a preformed catheter, 0.054% (P=.72). The study
      shows that serious ventricular arrhythmia occurs only rarely as a complication
      when coronary angiography is carried out using modern techniques and that
      imperfect manipulation of the catheter explains most episodes.

PMID- 18817687
TI  - The potential and reality of permanent his bundle pacing.
AB  - Right ventricular apex pacing can have deleterious effects. Our aims were to
      investigate how many patients referred for permanent pacing were suitable
      candidates for permanent His bundle pacing, and to determine the proportion in
      whom such pacing was successful. All cases of suprahisian block and most cases of
      infrahisian block (71.4%) were corrected by temporary His bundle pacing. However,
      permanent His bundle pacing was achieved in only 55% of cases in which it was
      attempted, and in only 35.4% of all possible cases.

PMID- 18817688
TI  - Infrahisian atrioventricular block secondary to radiotherapy.

PMID- 18817689
TI  - Nikaidoh procedure for the correction of transposition of the great arteries,
      ventricular septal defect and pulmonary stenosis.

PMID- 18817690
TI  - SPECT-CT of a Noncalcified Atherosclerotic Coronary Plaque.

PMID- 18817691
TI  - Ablation of idiopathic left ventricular tachycardia using remote magnetic
      navigation integrated with advanced mapping.

PMID- 18817692
TI  - Anomalous origin of the left coronary artery: the rare coincidence of the left
      anterior descending coronary artery originating from the pulmonary artery and the
      circumflex coronary artery originating from the right sinus of valsalva.

PMID- 18817693
TI  - Morphologies suggestive of V1 and V2 lead misplacement.

PMID- 18817697
TI  - [Reference values in the usual laboratory data for sub-Saharan immigrants.
      Importance in the management of infectious diseases].
AB  - BACKGROUND AND AIMS: The progressive increase in the number of immigrants to
      Spain in recent years has made it necessary for health-care professionals to be
      aware about the specific characteristics of this population. An attempt is made
      in this study to define the normal range of common laboratory values in healthy
      sub-Saharan adults. SUBJECTS AND METHODS: Common laboratory values were studied
      (blood cell counts, clotting tests and blood biochemistry values) and were
      measured in 150 sub-Saharan immigrants previously defined as healthy according to
      a complete health evaluation that included a clinical history, physical
      examination, serologic tests and study of stool parasites. These results were
      compared to those from a control group consisting of 81 age-and-sex matched
      healthy blood donors taken from the Spanish native population. RESULTS:
      Statistically significant differences were obtained in the following values. Mean
      corpuscular volume (MCV), red cell distribution width (RDW), total leukocytes,
      and serum levels of creatinine, uric acid, total protein content, creatin-kinase
      (CK), aspartate aminotransferase (AST), gamma-glutamyl-transpeptidase (GGT),
      Immunoglobulin G (IgG) and M (IgM). If evaluated according to the normal values
      in native people, a considerable percentage of healthy sub-Saharan immigrants
      would present <<abnormal>> values (with potential clinical relevance) in the
      following parameters. MCV, RDW, total leukocyte counts and serum levels of CK,
      IgG and IgM. CONCLUSIONS: A proper interpretation of the common laboratory values
      in sub-Saharan immigrants, and probably in other foreign collectives, requires a
      previously-established range of normality in these parameters for those
      populations in order to avoid diagnostic mistakes and inadequate work-up and
      management.

PMID- 18817698
TI  - [Primary care physicians behaviour on hypertensive patients with poor blood
      pressure control. The PRESCAP 2006 study].
AB  - INTRODUCTION: There is little information available on Therapeutic Inertia in
      Primary Care (PC). This study aimed to know the therapeutic behavior of the
      physician for uncontrolled hypertensive patients. PATIENTS AND METHODS: Cross
      sectional, multicenter study that included hypertensive patients of both genders,
      under pharmacological treatment who were recruited consecutively in the PC out
      patient clinic in all of Spain. Social-demographic, clinical and treatment data
      were recorded, as well as the motives for eventual therapeutic modification.
      Adequate BP control was considered when BP values were below 140/90 mmHg in
      general, and below 130/80 mmHg in diabetes, renal insufficiency or cardiovascular
      disease. RESULTS: A total of 10,520 patients (53.7% women) were included with
      average age of 64.6 (11.3 years). Of these, 44.4% the patients were receiving
      monotherapy and 55.6% were treated with combined therapy (two drugs 41.2%, three
      drugs 11.7%, and more than three 2.8%). Uncontrolled hypertension was found in
      58.6% (95% CI. 57.6-59.5) of the patients. Treatment was modified by physicians
      in 30.4% (95% CI. 29.2-31.6) of the uncontrolled patients, combination with
      another drug being the most frequent behavior (46.3%), followed by dose increase
      (26.1%), and antihypertensive drug switch (22.8%). The perception of the
      physician of good BP control was the factor most associated with not modifying
      the treatment in uncontrolled patients. CONCLUSIONS: Study results showed that
      the PC physician modified antihypertensive treatment in only 3 out of 10
      uncontrolled patients. When treatment modification was made, association of drugs
      was the most frequent behavior.

PMID- 18817699
TI  - [Risk factor control in the hypertensive patients with chronic ischemic heart
      disease attended in cardiologic outpatient clinics. The CINHTIA study].
AB  - OBJECTIVE: The CINHTIA study is a cross-sectional and multicentre survey designed
      to assess the clinical management of the hypertensive outpatients with chronic
      ischemic heart disease attended by cardiologists. PATIENTS AND METHODS: Patients
      > or = 18 years, with a diagnosis of hypertension and chronic ischemic heart
      disease, were included in the study. Patients with an acute coronary syndrome
      within the three months prior to the inclusion were excluded. Good blood pressure
      (BP) control was considered < 140/90 mmHg, < 130/80 mmHg for diabetics (ESH-ESC
      2003). LDL cholesterol (LDL-c) < 100 mg/dl (NCEP-ATP III) and fasting glucose
      between 90 and 130 mg/dl (ADA 2005) were considered as good control rates.
      RESULTS: A total of 2,024 patients (66.8+/-10.1 years; 31.7% women) were included
      in the study. Systolic BP was 142.7 +/- 17.9 mmHg and diastolic BP 81.8 +/- 11.3
      mmHg. 78.4% of the patients had dyslipidemia and 32.3% diabetes. Almost all the
      patients (99.7%) were taking at least one antihypertensive drug, beta blockers
      being the most frequent (67.1%). A total of 74.9% of the patients were taking
      lipid lowering drugs and 27.9% antidiabetics. BP was controlled in 40.5% of the
      patients, LDL-c in 30.6% of the dyslipidemic subgroup and fasting glucose in
      26.6% of the diabetics. CONCLUSIONS: In this high-risk population, the control
      rates of risk factors continues to remain low even though the majority of
      patients were taking several drugs.

PMID- 18817700
TI  - [Pain and increased diameter of left lower limb].

PMID- 18817701
TI  - [Hyperkeratosic plaques located exclusively on hand palms and sole of feet].

PMID- 18817695
TI  - [Cardiovascular risk in subjects with high probability of metabolic syndrome and
      insulin resistance. DESIRE study].
AB  - INTRODUCTION AND OBJECTIVES: The metabolic syndrome is an association of closely
      related alterations. The main objective of this study is to know the frequency of
      the metabolic syndrome and insulin resistance, and their role as cardiovascular
      risk indicators in an adult population assigned to Primary Care centers in Spain.
      METHODS: Subjects > or = 45 years with basal glycemia > or = 90 mg/dl and
      abdominal circumference > or = 94 cm (men) or > or = 80 cm (women). ATP III
      modified-criteria were used for the metabolic syndrome and HOMA index > 3.29 was
      used for insulin resistance. Cardiovascular risk was estimated by the Framingham
      and SCORE models. RESULTS: A total of 2,341 subjects (62 +/- 10 years; 44.6%
      males) were included. Frequency of metabolic syndrome and insulin resistance was
      54.6% (52.5; 56.8) and 56.6% (54.5; 58.7) respectively. Metabolic syndrome was
      associated to a higher cardiovascular risk score with both Framingham (16 [15;
      16] vs 11 [11; 12] p < 0.0001) and SCORE (2.7 [2.4; 3] vs 2.4 [2.1; 2.8]; p =
      0.006) models. The results were similar for the presence of insulin resistance.
      CONCLUSIONS: Metabolic syndrome and insulin resistance are cardiovascular risk
      predictors. Early identification of metabolic syndrome by the use of simple
      clinical measures (basal glycemia and waist circumference) would make the
      intervention on the different disorders of metabolic syndrome possible.

PMID- 18817702
TI  - [Axillary lymphadenopathies in a patient with a background of melanoma].

PMID- 18817703
TI  - [Pruritus and creeping skin eruption after stay in the Pireo].

PMID- 18817704
TI  - [Inverted 3-sign and pyrosis].

PMID- 18817705
TI  - [Atrial fibrillation. Monitoring of rhythm versus monitoring of ventricular
      response].
AB  - Atrial fibrillation is the most frequent supraventricular arrhythmia. The goals
      for the treatment of this arrhythmia are symptom control and reducing
      cardiovascular morbidity and mortality. In elderly patients with no symptoms we
      must indicate therapy based on rate control. On the other side, in young patients
      without heart disease, those very symptomatic or if atrial fibrillation causes a
      significant hemodynamic and functional deterioration we must try, at least
      initially, a strategy of maintaining sinus rhythm. In the future, we hope that
      the development of new anti-arrhythmic drugs safer and more effective, and
      refining catheter ablation will lead to increased therapeutic efficacy in
      patients with atrial fibrillation.

PMID- 18817706
TI  - [Plasmacytoid dendritic cell leukemia/lymphoma].

PMID- 18817707
TI  - [Fatal pulmonary edema in patient with enterovirus meningitis].

PMID- 18817708
TI  - [Factitious fever: a disease without imaging diagnosis].

PMID- 18817709
TI  - [What is your profession?].

PMID- 18817710
TI  - [Pure red cell aplasia secondary to carbamazepine].

PMID- 18817711
TI  - [Spontaneous urinoma resolved with bladder catheter].

PMID- 18817712
TI  - [Correlations between clinical and histological aspects in nasal polyposis].
AB  - INTRODUCTION: The histological study of nasal polyps does not reveal any specific
      lesions but eosinophilic infiltration nasal mucosae seems to be characteristic of
      nasal polyposis. The aim of this work is to study possible links between certain
      histological and clinical aspects in nasal polyposis. Furthermore, we attempt to
      compare the quantification of tissue eosinophilia according to the number of
      eosinophils per field with the percentage figure obtained with respect to the
      total of inflammatory cells. MATERIAL AND METHOD: We have studied 40 patients
      with idiopathic bilateral nasal polyposis, assessing the correlations between
      various clinical aspects such as their endoscopic and radiological status,
      association with asthma and intolerance to NSAIDs, against histological aspects
      of nasal polyps such as the frequency of metaplasia, fibrosis and the degree of
      eosinophilic infiltration. A group of 12 healthy subjects allowed comparison of
      our results with healthy nasal mucosa. RESULTS: Tissue eosinophilia correlates
      statistically with clinical staging and tends to be higher in patients with ASA
      triad. The quantitative measurement of tissue eosinophilia (number of eosinophils
      per field) correlates with the percentage figure obtained (with respect to the
      total number of inflammatory cells in the infiltrate). CONCLUSIONS: Eosinophil
      infiltration of the nasal mucosa is, together with oedema, the most constant
      histological characteristic of nasal polyposis and seems to be an important
      factor in the clinical behaviour of sinonasal polyposis. Quantitative measurement
      of tissue eosinophilia is easier and quicker to perform and equivalent to
      percentage evaluation.

PMID- 18817713
TI  - [Prognostic factors for definitive hypoparathyroidism following total
      thyroidectomy].
AB  - INTRODUCTION AND OBJECTIVE: Hypocalcaemia, transient in most cases, is the main
      complication after thyroid gland surgery with regard to functional impairment of
      the parathyroid glands or other reversible factors. Sixty-seven patients who
      underwent thyroidectomy were evaluated to identify potential clinical,
      pathological and surgical factors that might be predictive for frank
      hypocalcaemia following total thyroidectomy. METHODS: Serum samples were taken
      preoperatively and postoperatively to measure total calcium levels. Patients'
      plasma calcium levels were recorded post-operatively along with such factors as
      age, gender, thyroid function, definitive pathology-based diagnosis, accidental
      removal and auto-transplantation of parathyroid glands, re-intervention to
      identify risk factors for the development of definitive hypoparathyroidism (DH).
      All comparisons were made between patients with hypocalcaemia and normal levels
      of post-operative calcaemia. RESULTS: Transient acute hypocalcaemia was
      identified in 25 of 67 patients (43.3 %). DH was identified in 8 (11 %) patients.
      CONCLUSIONS: Our study revealed that the only risk factor for DH was a calcium
      level of less than 7.5 mg/dL within the first 24 hours following surgery; this is
      a reliable, inexpensive and rapid parameter that is highly predictive of the
      onset of HD. No statistical significant associations were detected with other
      factors such as thyroid function, histology, accidental removal or
      autotransplantation of parathyroid glands, thus it is possible to state that
      careful manipulation of the parathyroid to preserve the periglandular
      vascularization is of vital importance to ensure correct post-operative
      functionality.

PMID- 18817714
TI  - [Clinical efficacy and polysomnography of adenotonsillectomy in the treatment of
      sleep-related respiratory disorders in children].
AB  - INTRODUCTION: If sleep-related breathing disorders in children are not treated
      quickly, they may be harmful to the child's future development. The best
      diagnostic test is polysomnography, since clinical assessments alone are not
      enough. Adenotonsillectomy is the most effective and widespread treatment for
      such disorders. OBJECTIVE: To assess clinical data on sleep-related breathing
      disorders, particularly in relation to behaviour and neurocognition, their long
      term resolution with surgery and correlation with PSG data. METHOD: Prospective
      study with 73 children between 3 and 11 years of age, attending a special clinic
      for sleep-related breathing disorders. A medical history questionnaire was given
      to the parents, which included questions on the child's sleep patterns,
      respiratory disorders and behavioural and neurocognitive changes, and a
      polysomnography was carried out. Cases requiring surgery were monitored after 9
      months by means of a further questionnaire and a follow-up polysomnography.
      RESULTS: Of the 73 children tested, 100 % snore, 87.5 % display objective apnoeas
      and 89 % suffer from nasal congestion. Drowsiness during the day was reported in
      only 28 %. Over 50 % of cases report aggressiveness or hyperactivity, while 41 %
      have concentration difficulties. In 61 of the 73 cases (83.6 %) given a pre
      operative polysomnography, the mean apnoea-hypopnoea index was 6.44 (4.44).
      Postoperative follow-up is available for 44 cases, 29 of them with
      polysomnography. The resolution of clinical symptoms is highly satisfactory in
      these cases, but 5 patients (17.2 %) still have an apnoea-hypopnoea index of more
      than 3. CONCLUSIONS: Adenotonsillectomy is effective in curing the majority of
      sleep-related respiratory disorder symptoms in children. However, a significant
      percentage of cases display a persistent polysomnographic change. Long-term
      postoperative monitoring is recommended in such cases.

PMID- 18817715
TI  - [Static posturography versus clinical tests in elderly people with vestibular
      pathology].
AB  - INTRODUCTION AND OBJECTIVES: Balance can be quantified by clinical tests and
      through instrumental studies. The objective of this paper is to determine the
      correlation between static posturography and 4 clinical tests of balance in
      elderly people with vestibular disorders and to identify its capability to
      discriminate the groups studied. METHODS: 60 patients with vestibular disorders
      and 60 healthy subjects performed 4 clinical tests (one leg standing with opened
      eyes, Timed Up and Go, Tinetti and Berg tests) and a static posturography
      analysis (NedSVE/IBV system) under 4 conditions: Romberg Test, Eyes Open (REO),
      Romberg Test, Eyes Closed (REC), Romberg Test on Foam with Eyes Open (RFEO), and
      Romberg Test on Foam with Eyes Closed (RFEC). RESULTS: RFEO correlated best with
      the clinical tests and RFEC was the worst. RFEO distinguished between healthy
      individuals and decompensated patients. CONCLUSIONS: RFEO gave the best
      information about postural balance in the elderly. RFEC was not useful. Static
      posturography can be useful to distinguish vestibular compensation status.

PMID- 18817716
TI  - [Procalcitonin plasma levels do not alter after uncomplicated skull base
      surgery].
AB  - INTRODUCTION: Procalcitonin (PCT) is the precursor of the calcitonin hormone.
      Plasma concentrations of procalcitonin increase in systemic inflammation,
      especially when they are caused by bacterial infections. The aim of this study is
      to analyze and validate the baseline PCT concentrations after different types of
      skull base surgery and to test the hypothesis that PCT could be useful as an
      early marker of post-operative infectious complications, especially meningitis.
      MATERIAL AND METHOD: This is a prospective study of sixteen patients who
      underwent skull base surgery. PCT and C-reactive protein plasma levels,
      leukocytes and clinical symptoms were registered pre-operatively and 1, 2, and 5
      days post-operatively. RESULTS: All patients had a normal post-operative course
      without clinical signs of infection. PCT concentrations did not increase above
      the normal range in any case. CONCLUSIONS: As PCT plasma concentration does not
      notably increase despite the inflammatory phenomena associated with uncomplicated
      skull base surgery, it may be possible to use PCT as an early marker for non
      invasive study of post-operative infectious complications.

PMID- 18817717
TI  - [Is it necessary to perform neck dissections as a staged procedure in laser
      supraglottic laryngectomy?].
AB  - INTRODUCTION AND OBJECTIVES: Endoscopic CO2 laser supraglottic laryngectomy has
      similar oncological results to the classical open approach. Treatment of the neck
      is of paramount importance in these tumours and it is usually performed as a
      staged procedure. The aim of this work is to ascertain if it is safe to perform
      the neck dissections at the same time as the laser supraglottic laryngectomy.
      METHODS: Twenty-four patients with supraglottic epidermoid carcinoma, who
      underwent laser CO2 supraglottic laryngectomy and bilateral neck dissection, were
      studied. In 12 patients the neck dissections were performed as a staged procedure
      (a mean of 15 days after the laryngectomy), and in the remaining 12 they were
      performed simultaneously. Both groups were comparable in terms of age and the
      staging of their tumours. RESULTS: No significant differences were found between
      the groups in terms of surgical complications (P=.18), tracheostomy rates (1 post
      operative tracheostomy in each group; P=.99), aspiration pneumonia (P=.48), and
      the mean for nasogastric tube feeding (P=.36). The mean hospital stay was five
      days longer in the group with staged neck dissections. CONCLUSIONS: It is a safe
      procedure to perform neck dissections at the same time as the supraglottic
      laryngectomy. We did not find any increase in the complications rate and the
      hospital stay was shorter.

PMID- 18817718
TI  - [Treatment of chin deformities].
AB  - Facial beauty depends on the form, proportion and position of its various units.
      The chin is the most prominent element of the lower third of the face, both in
      the frontal view and in profile. The surgical approach to chin deformities did
      not start until the second half of the twentieth century. The development of
      silicone prostheses and the emergence of sliding genioplasty offered surgeons a
      whole new range of options to modify the size and position of the chin. We have
      performed a historical review of chin surgery, the multiple aesthetic analyses
      available and the advantages and disadvantages of the different alloplastic
      materials and osteotomies. To do so, a comprehensive search through current
      scientific literature on the topic has been carried out, focusing on large
      series, long-term follow-up studies, research in animal models and medical
      evidence. As happens in almost any topic in facial plastic surgery, no strong
      evidence useful in ENT practice for handling chin deformities can be found in
      today's scientific literature. Ethnicity influences the aesthetic analysis; the
      type and degree of deformity to be corrected will determine the allo-plastic
      augmentation of the chin or the suitability of osteotomy. Porous polyethylene
      (Medpor, Porex Surgical, Newman, Ca, USA) and solid silicone (Silastic, Michigan
      Medical Corporation, Santa Barbara, Ca, USA) show a clear advantage over other
      alloplastic materials. Moderate-to-severe retrogenia benefits from sliding
      genioplasty strategies rather than prosthetic enlargement.

PMID- 18817719
TI  - [Compound odontoma as a cause of chronic maxillary sinusitis].
AB  - Sinusitis of dental origin is a relatively frequent entity, but the presence of
      an odontoma in the sinus as a source of this pathology is exceptional. Here we
      present a case of a young patient who presented chronic maxillary sinusitis over
      2 years, originating in an odontoma located in the sinus drainage area.

PMID- 18817720
TI  - [PANDAS Syndrome: a new tonsillectomy indication?].
AB  - PANDAS Syndrome (Paediatric Autoimmune Neuropsychiatric Disorders Associated with
      Streptococcus) is a rare disease described in 1998. In this disease, there is a
      relationship between group A beta haemolytic streptococcal tonsil infections and
      the exacerbation of neuropsychiatric disorders. A case report of a 9-year-old
      child with PANDAS syndrome is presented. This child has had no further symptoms
      after tonsillectomy. The understanding about PANDAS syndrome and tonsillectomy is
      reviewed.

PMID- 18817721
TI  - [Basilingual thyroglossal cyst: an infrequent cause of Dysphagia and dyspnoea].

PMID- 18817723
TI  - A single sensory neuron directs both attractive and repulsive odor preferences.
AB  - Animal behaviors are subjected to innate preferences, which are usually encoded
      by dedicated sensory neurons. In this issue of Neuron, Tsunozaki and colleagues
      show that one olfactory neuron in Caenorhabditis elegans produces two opposing
      preferences to an odor by regulating cGMP and PKC signaling.

PMID- 18817722
TI  - Potential associations between fecal shedding of Salmonella in feedlot cattle
      treated for apparent respiratory disease and subsequent adverse health outcomes.
AB  - A prospective cohort study was used to assess whether Salmonella fecal shedding
      in commercial feedlot cattle treated with antimicrobials for respiratory disease
      was associated with subsequent adverse health outcomes. Feces were collected per
      rectum from cattle that were examined for apparent respiratory disease, had a
      rectal temperature > or = 40 degrees C, and subsequently received antimicrobial
      treatment. Salmonella were recovered from 918 (73.7%) of 1 245 fecal samples and
      weekly prevalence estimates ranged from 49 to 100% over the 3-month study.
      Genotypic and phenotypic characteristics of Salmonella strains in the population
      were determined. Serogroup E Salmonella were most common (73.3%), followed by C1
      (11.0%), C3 (8.6%), and B (1.1%). Predominant serotypes were Orion (46.5%),
      Anatum (19.8%), Kentucky (8.7%), Montevideo (7.5%), and Senftenberg (4.9%). Few
      isolates (36/918) were positive for antimicrobial resistance-associated integron
      gene intI1. Phenotypic susceptibility was associated with isolate intI1 status.
      Crude re-pull, re-treatment and case fatality risks were higher for cattle that
      were Salmonella-positive versus -negative at initial treatment, but not
      statistically different on multivariable analysis. However, case fatality risk
      was higher for cattle shedding Group B Salmonella than for cattle shedding other
      serogroups. Lots (groups) with a higher Salmonella prevalence at first treatment
      had a higher proportion of mortalities occur in a hospital pen, higher overall re
      treatment risks, and were more likely to be sampled later in the study. Results
      indicate a high prevalence of Salmonella in this population of cattle treated for
      apparent respiratory disease, but that effects associated with clinical outcomes
      may depend on the Salmonella strain.

PMID- 18817724
TI  - Emotional regulation, or: how I learned to stop worrying and love the nucleus
      accumbens.
AB  - How does the brain control emotion? In this issue of Neuron, Wager et al. use a
      novel mediation analysis of neuroimaging data to show two independent pathways
      for the control of emotion by the prefrontal cortex: a path through the amygdala
      predicts a greater negative emotional response, and a path through the nucleus
      accumbens/ventral striatum predicts a greater positive response.

PMID- 18817725
TI  - Drosophila olfaction: the end of stereotypy?
AB  - Recent work has demonstrated substantial wiring and functional stereotypy in the
      fly olfactory system. In this issue of Neuron, Murthy et al. demonstrate that in
      the mushroom body, a site of olfactory associative learning, this initial
      peripheral stereotypy gives way to functionally nonstereotyped circuits.

PMID- 18817726
TI  - From synapse to nucleus: calcium-dependent gene transcription in the control of
      synapse development and function.
AB  - One of the unique characteristics of higher organisms is their ability to learn
      and adapt to changes in their environment. This plasticity is largely a result of
      the brain's ability to convert transient stimuli into long-lasting alterations in
      neuronal structure and function. This process is complex and involves changes in
      receptor trafficking, local mRNA translation, protein turnover, and new gene
      synthesis. Here, we review how neuronal activity triggers calcium-dependent gene
      expression to regulate synapse development, maturation, and refinement.
      Interestingly, many components of the activity-dependent gene expression program
      are mutated in human cognitive disorders, which suggest that this program is
      essential for proper brain development and function.

PMID- 18817727
TI  - Multiple roles of calcium ions in the regulation of neurotransmitter release.
AB  - The intracellular calcium concentration ([Ca(2+)]) has important roles in the
      triggering of neurotransmitter release and the regulation of short-term
      plasticity (STP). Transmitter release is initiated by quite high concentrations
      within microdomains, while short-term facilitation is strongly influenced by the
      global buildup of "residual calcium." A global rise in [Ca(2+)] also accelerates
      the recruitment of release-ready vesicles, thereby controlling the degree of
      short-term depression (STD) during sustained activity, as well as the recovery of
      the vesicle pool in periods of rest. We survey data that lead us to propose two
      distinct roles of [Ca(2+)] in vesicle recruitment: one accelerating "molecular
      priming" (vesicle docking and the buildup of a release machinery), the other
      promoting the tight coupling between releasable vesicles and Ca(2+) channels.
      Such coupling is essential for rendering vesicles sensitive to short [Ca(2+)]
      transients, generated during action potentials.

PMID- 18817728
TI  - Control of K(Ca) channels by calcium nano/microdomains.
AB  - Transient elevations in cytoplasmic Ca(2+) trigger a multitude of Ca(2+)
      dependent processes in CNS neurons and many other cell types. The specificity,
      speed, and reliability of these processes is achieved and ensured by tightly
      restricting Ca(2+) signals to very local spatiotemporal domains, "Ca(2+) nano-
      and microdomains," that are centered around Ca(2+)-permeable channels. This
      arrangement requires that the Ca(2+)-dependent effectors reside within these
      spatial boundaries where the properties of the Ca(2+) domain and the Ca(2+)
      sensor of the effector determine the channel-effector activity. We use Ca(2+)
      activated K(+) channels (K(Ca)) with either micromolar (BK(Ca) channels) or
      submicromolar (SK(Ca) channels) affinity for Ca(2+) ions to provide distance
      constraints for Ca(2+)-effector coupling in local Ca(2+) domains and review their
      significance for the cell physiology of K(Ca) channels in the CNS. The results
      may serve as a model for other processes operated by local Ca(2+) domains.

PMID- 18817729
TI  - Calcium channel regulation and presynaptic plasticity.
AB  - Voltage-gated calcium (Ca(2+)) channels initiate release of neurotransmitters at
      synapses, and regulation of presynaptic Ca(2+) channels has a powerful influence
      on synaptic strength. Presynaptic Ca(2+) channels form a large signaling complex,
      which targets synaptic vesicles to Ca(2+) channels for efficient release and
      mediates Ca(2+) channel regulation. Presynaptic plasticity regulates synaptic
      function on the timescale of milliseconds to minutes in response to
      neurotransmitters and the frequency of action potentials. This article reviews
      the regulation of presynaptic Ca(2+) channels by effectors and regulators of
      Ca(2+) signaling and describes the emerging evidence for a critical role of
      Ca(2+) channel regulation in control of neurotransmission and in presynaptic
      plasticity. Failure of function and regulation of presynaptic Ca(2+) channels
      leads to migraine, ataxia, and potentially other forms of neurological disease.
      We propose that presynaptic Ca(2+) channels serve as the regulatory node in a
      dynamic, multilayered signaling network that exerts short-term control of
      neurotransmission in response to synaptic activity.

PMID- 18817730
TI  - Calcium signaling in dendrites and spines: practical and functional
      considerations.
AB  - Changes in intracellular calcium (Ca) concentration following synaptic and
      suprathreshold activity are mediated by a wide range of sources and contribute to
      the regulation of myriad neuronal functions. The development of Ca imaging
      techniques has dramatically increased our understanding of the complex
      interactions between different Ca sources and their ability to produce spatial
      and temporal specificity of signaling, even within small cellular compartments
      such as dendrites and dendritic spines. However, as the use of Ca imaging has
      become more prevalent, the need to exercise care in the experimental methodology
      and interpretation of data has also grown. In this review, we discuss the recent
      progress made using imaging methods in understanding dendritic Ca signaling and
      also describe a quantitative framework for using fluorescent indicators to
      experimentally measure and interpret changes in intracellular Ca.

PMID- 18817732
TI  - What is the role of astrocyte calcium in neurophysiology?
AB  - Astrocytes comprise approximately half of the volume of the adult mammalian brain
      and are the primary neuronal structural and trophic supportive elements.
      Astrocytes are organized into distinct nonoverlapping domains and extend
      elaborate and dense fine processes that interact intimately with synapses and
      cerebrovasculature. The recognition in the mid 1990s that astrocytes undergo
      elevations in intracellular calcium concentration following activation of G
      protein-coupled receptors by synaptically released neurotransmitters demonstrated
      not only that astrocytes display a form of excitability but also that astrocytes
      may be active participants in brain information processing. The roles that
      astrocytic calcium elevations play in neurophysiology and especially in
      modulation of neuronal activity have been intensely researched in recent years.
      This review will summarize the current understanding of the function of
      astrocytic calcium signaling in neurophysiological processes and discuss areas
      where the role of astrocytes remains controversial and will therefore benefit
      from further study.

PMID- 18817731
TI  - Calmodulin-kinases: modulators of neuronal development and plasticity.
AB  - In the nervous system, many intracellular responses to elevated calcium are
      mediated by CaM kinases (CaMKs), a family of protein kinases whose activities are
      initially modulated by binding Ca(2+)/calmodulin and subsequently by protein
      phosphorylation. One member of this family, CaMKII, is well-established for its
      effects on modulating synaptic plasticity and learning and memory. However,
      recent studies indicate that some actions on neuronal development and function
      attributed to CaMKII may instead or in addition be mediated by other members of
      the CaMK cascade, such as CaMKK, CaMKI, and CaMKIV. This review summarizes key
      neuronal functions of the CaMK cascade in signal transduction, gene
      transcription, synaptic development and plasticity, and behavior. The technical
      challenges of mapping cellular protein kinase signaling pathways are also
      discussed.

PMID- 18817733
TI  - Deletion of Mecp2 in Sim1-expressing neurons reveals a critical role for MeCP2 in
      feeding behavior, aggression, and the response to stress.
AB  - Rett Syndrome (RTT) is an autism spectrum disorder caused by mutations in the X
      linked gene encoding methyl-CpG binding protein 2 (MeCP2). In order to map the
      neuroanatomic origins of the complex neuropsychiatric behaviors observed in
      patients with RTT and to uncover endogenous functions of MeCP2 in the
      hypothalamus, we removed Mecp2 from Sim1-expressing neurons in the hypothalamus
      using Cre-loxP technology. Loss of MeCP2 in Sim1-expressing neurons resulted in
      mice that recapitulated the abnormal physiological stress response that is seen
      upon MeCP2 dysfunction in the entire brain. Surprisingly, we also uncovered a
      role for MeCP2 in the regulation of social and feeding behaviors since the Mecp2
      conditional knockout (CKO) mice were aggressive, hyperphagic, and obese. This
      study demonstrates that deleting Mecp2 in a defined brain region is an excellent
      approach to map the neuronal origins of complex behaviors and provides new
      insight about the function of MeCP2 in specific neurons.

PMID- 18817734
TI  - A behavioral switch: cGMP and PKC signaling in olfactory neurons reverses odor
      preference in C. elegans.
AB  - Innate chemosensory preferences are often encoded by sensory neurons that are
      specialized for attractive or avoidance behaviors. Here, we show that one
      olfactory neuron in Caenorhabditis elegans, AWC(ON), has the potential to direct
      both attraction and repulsion. Attraction, the typical AWC(ON) behavior, requires
      a receptor-like guanylate cyclase GCY-28 that acts in adults and localizes to
      AWC(ON) axons. gcy-28 mutants avoid AWC(ON)-sensed odors; they have normal odor
      evoked calcium responses in AWC(ON) but reversed turning biases in odor
      gradients. In addition to gcy-28, a diacylglycerol/protein kinase C pathway that
      regulates neurotransmission switches AWC(ON) odor preferences. A behavioral
      switch in AWC(ON) may be part of normal olfactory plasticity, as odor
      conditioning can induce odor avoidance in wild-type animals. Genetic
      interactions, acute rescue, and calcium imaging suggest that the behavioral
      reversal results from presynaptic changes in AWC(ON). These results suggest that
      alternative modes of neurotransmission can couple one sensory neuron to opposite
      behavioral outputs.

PMID- 18817735
TI  - A screen of cell-surface molecules identifies leucine-rich repeat proteins as key
      mediators of synaptic target selection.
AB  - In Drosophila embryos and larvae, a small number of identified motor neurons
      innervate body wall muscles in a highly stereotyped pattern. Although genetic
      screens have identified many proteins that are required for axon guidance and
      synaptogenesis in this system, little is known about the mechanisms by which
      muscle fibers are defined as targets for specific motor axons. To identify
      potential target labels, we screened 410 genes encoding cell-surface and secreted
      proteins, searching for those whose overexpression on all muscle fibers causes
      motor axons to make targeting errors. Thirty such genes were identified, and a
      number of these were members of a large gene family encoding proteins whose
      extracellular domains contain leucine-rich repeat (LRR) sequences, which are
      protein interaction modules. By manipulating gene expression in muscle 12, we
      showed that four LRR proteins participate in the selection of this muscle as the
      appropriate synaptic target for the RP5 motor neuron.

PMID- 18817736
TI  - AMPA receptor subunit-specific regulation by a distinct family of type II TARPs.
AB  - AMPA-type glutamate receptors (GluRs) play major roles in excitatory synaptic
      transmission. Neuronal AMPA receptors comprise GluR subunits and transmembrane
      AMPA receptor regulatory proteins (TARPs). Previous studies identified five
      mammalian TARPs, gamma-2 (or stargazin), gamma-3, gamma-4, gamma-7, and gamma-8,
      that enhance AMPA receptor function. Here, we classify gamma-5 as a distinct
      class of TARP that modulates specific GluR2-containing AMPA receptors and
      displays properties entirely dissimilar from canonical TARPs. Gamma-5 increases
      peak currents and decreases the steady-state currents selectively from GluR2
      containing AMPA receptors. Furthermore, gamma-5 increases rates of GluR2
      deactivation and desensitization and decreases glutamate potency. Remarkably, all
      effects of gamma-5 require editing of GluR2 mRNA. Unlike other TARPs, gamma-5
      modulates GluR2 without promoting receptor trafficking. We also find that gamma-7
      regulation of GluR2 is dictated by mRNA editing. These data establish gamma-5 and
      gamma-7 as a separate family of "type II TARPs" that impart distinct
      physiological features to specific AMPA receptors.

PMID- 18817737
TI  - Evolutionary conserved role for TARPs in the gating of glutamate receptors and
      tuning of synaptic function.
AB  - Neurotransmission in the brain is critically dependent on excitatory synaptic
      signaling mediated by AMPA-class ionotropic glutamate receptors (AMPARs). AMPARs
      are known to be associated with Transmembrane AMPA receptor Regulatory Proteins
      (TARPs). In vertebrates, at least four TARPs appear to have redundant roles as
      obligate chaperones for AMPARs, thus greatly complicating analysis of TARP
      participation in synaptic function. We have overcome this limitation by
      identifying and mutating the essential set of TARPs in C. elegans (STG-1 and STG
      2). In TARP mutants, AMPAR-mediated currents and worm behaviors are selectively
      disrupted despite apparently normal surface expression and clustering of the
      receptors. Reconstitution experiments indicate that both STG-1 and STG-2 can
      functionally substitute for vertebrate TARPs to modify receptor function. Thus,
      we show that TARPs are obligate auxiliary subunits for AMPARs with a primary,
      evolutionarily conserved functional role in the modification of current kinetics.

PMID- 18817738
TI  - Testing odor response stereotypy in the Drosophila mushroom body.
AB  - The mushroom body is an insect brain structure required for olfactory learning.
      Its principal neurons, the Kenyon cells (KCs), form a large cell population. The
      neuronal populations from which their olfactory input derives (olfactory sensory
      and projection neurons) can be identified individually by genetic, anatomical,
      and physiological criteria. We ask whether KCs are similarly identifiable
      individually, using genetic markers and whole-cell patch-clamp in vivo. We find
      that across-animal responses are as diverse within the genetically labeled subset
      as across all KCs in a larger sample. These results combined with those from a
      simple model, using projection neuron odor responses as inputs, suggest that the
      precise circuit specification seen at earlier stages of odor processing is likely
      absent among the mushroom body KCs.

PMID- 18817739
TI  - Sustained CPEB-dependent local protein synthesis is required to stabilize
      synaptic growth for persistence of long-term facilitation in Aplysia.
AB  - The time course of the requirement for local protein synthesis in the
      stabilization of learning-related synaptic growth and the persistence of long
      term memory was examined using Aplysia bifurcated sensory neuron-motor neuron
      cultures. We find that, following repeated pulses of serotonin (5-HT), the local
      perfusion of emetine, an inhibitor of protein synthesis, or a TAT-AS
      oligonucleotide directed against ApCPEB blocks long-term facilitation (LTF) at
      either 24 or 48 hr and leads to a selective retraction of newly formed sensory
      neuron varicosities induced by 5-HT. By contrast, later inhibition of local
      protein synthesis, at 72 hr after 5-HT, has no effect on either synaptic growth
      or LTF. These results define a specific stabilization phase for the storage of
      long-term memory during which newly formed varicosities are labile and require
      sustained CPEB-dependent local protein synthesis to acquire the more stable
      properties of mature varicosities required for the persistence of LTF.

PMID- 18817740
TI  - Prefrontal-subcortical pathways mediating successful emotion regulation.
AB  - Although prefrontal cortex has been implicated in the cognitive regulation of
      emotion, the cortical-subcortical interactions that mediate this ability remain
      poorly understood. To address this issue, we identified a right ventrolateral
      prefrontal region (vlPFC) whose activity correlated with reduced negative
      emotional experience during cognitive reappraisal of aversive images. We then
      applied a pathway-mapping analysis on subcortical regions to locate mediators of
      the association between vlPFC activity and reappraisal success (i.e., reductions
      in reported emotion). Results identified two separable pathways that together
      explained approximately 50% of the reported variance in self-reported emotion:
      (1) a path through nucleus accumbens that predicted greater reappraisal success,
      and (2) a path through ventral amygdala that predicted reduced reappraisal
      success (i.e., more negative emotion). These results provide direct evidence that
      vlPFC is involved in both the generation and regulation of emotion through
      different subcortical pathways, suggesting a general role for this region in
      appraisal processes.

PMID- 18817741
TI  - Identification of low-abundance alternatively spliced mRNA variants by exon
      exclusive reverse transcriptase polymerase chain reaction.
AB  - Alternative splicing of messenger RNA (mRNA) precursors generates multiple
      transcripts from a single primary transcript. Identification and verification of
      splice variants and cloning of the corresponding isoforms is crucial for
      analyzing gene expression and understanding the related functions. For a specific
      gene, the abundance of the transcripts produced can vary significantly and is
      subject to various regulations. It can be difficult to detect low-level splicing
      variants when others are present in high abundance. Here we describe a method for
      the amplification of low-abundance mRNA splicing variants for such situations.
      This method introduces a hydrolysis step prior to the conventional reverse
      transcriptase polymerase chain reaction (RT-PCR). After the transcripts are
      reverse-transcripted into complementary DNA (cDNA), the cDNA of high-abundance
      transcript is suppressed from amplification by cleavage at the chosen exon to
      enhance the amplification of the low-abundance transcripts that do not have the
      targeted exon and are normally undetectable. We provide two examples to
      illustrate the detection of low-abundance splicing variants from two genes.

PMID- 18817742
TI  - 3,4-Dihydroxyphenylalanine gel diffusion assay for polyphenol oxidase
      quantification.
AB  - We have developed a simple, inexpensive plate assay to detect and quantify
      polyphenol oxidase (PPO) activity from different origins. The logarithm of enzyme
      activity is linearly correlated with the diameter of the dark, l-3,4
      dihydroxyphenylalanine (l-DOPA) oxidized circles produced in the gel, thereby
      allowing quantification of PPO. Moreover, precision and high reproducibility of
      the assay were confirmed by statistical analysis.

PMID- 18817743
TI  - A dual-probe hybridization method for reducing variability in single nucleotide
      polymorphism analysis with oligonucleotide microarrays.
AB  - DNA microarray technology has become powerful and popular in mutation/single
      nucleotide polymorphism (SNP) discovery and genotyping. However, this method is
      often associated with considerable signal noise of nonbiological origin that may
      compromise the data quality and interpretation. To achieve a high degree of
      reliability, accuracy, and sensitivity in data analysis, an effective
      normalization method to minimize the technical variability is highly desired. In
      the current study, a simple and robust normalization method is described. The
      method is based on introduction of a reference probe coimmobilized with SNP
      probes on the microarray for a dual-probe hybridization (DPH) reaction. The
      reference probe is used as an intraspot control for the customized microarrays.
      Using this method, the interassay coefficient of variation (CV) was reduced
      significantly by approximately 10%. After DPH normalization, the CVs and ranges
      of the ratios were reduced by two to five times. The relative magnitudes of
      variation of different sources were also analyzed by analysis of variance. Glass
      slides were shown to contribute the most to the variance, whereas sampling and
      residual errors had relatively modest contribution. The results showed that this
      DPH-based spot-dependent normalization method is an effective solution for
      reducing experimental variation associated with microarray genotyping data.

PMID- 18817744
TI  - Polyaniline-carbon nanotube composite film for cholesterol biosensor.
AB  - Nanocomposite film composed of polyaniline (PANI) and multiwalled carbon
      nanotubes (MWCNT), prepared electrophoretically onto indium tin oxide (ITO)
      coated glass plate, was used for covalent immobilization of cholesterol oxidase
      (ChOx) via N-ethyl-N'-(3-dimethylaminopropyl) carbodiimide (EDC) and N
      hydroxysuccinimide (NHS) chemistry. Results of linear sweep voltammetric
      measurements reveal that ChOx/PANI-MWCNT/ITO bioelectrode can detect cholesterol
      in the range of 1.29 to 12.93 mM with high sensitivity of 6800 nA mM(-1) and a
      fast response time of 10 s. Photometric studies for ChOx/PANI-MWCNT/ITO
      bioelectrode indicate that it is thermally stable up to 45 degrees C and has a
      shelf life of approximately 12 weeks when stored at 4 degrees C. The results of
      these studies have implications for the application of this interesting matrix
      (PANI-MWCNT) toward the development of other biosensors.

PMID- 18817745
TI  - Biochemical characterization of L-DOPA 2,3-dioxygenase, a single-domain type I
      extradiol dioxygenase from lincomycin biosynthesis.
AB  - L-DOPA-2,3-dioxygenase from Streptomyces lincolnensis is a single-domain type I
      extradiol dioxygenase of the vicinal oxygen chelate superfamily and catalyzes the
      second step in the metabolism of tyrosine to the propylhygric acid moiety of the
      antibiotic, lincomycin. S. lincolnensis L-DOPA-2,3-dioxygenase was overexpressed,
      purified and reconstituted with Fe(II). The activity of L-DOPA-2,3-dioxygenase
      was kinetically characterized with L-DOPA (K(M)=38 microM, k(cat)=4.2 min(-1))
      and additional catecholic substrates including dopamine, 3,4
      dihydroxyhydrocinnamic acid, catechol and D-DOPA. 3,4-Dihydroxyphenylacetic acid
      was characterized as a competitive inhibitor of the enzyme (K(i) =2.2 mM). Site
      directed mutagenesis and its effects on enzymatic activity were used to identify
      His14 and His70 as iron ligands.

PMID- 18817746
TI  - Spectroscopic studies of the chlorophyll d containing photosystem I from the
      cyanobacterium, Acaryochloris marina.
AB  - Absorbance difference spectroscopy and redox titrations have been applied to
      investigate the properties of photosystem I from the chlorophyll d containing
      cyanobacterium Acaryochloris marina. At room temperature, the (P740(+)-P740) and
      (F(A/B)(-)-F(A/B)) absorbance difference spectra were recorded in the range
      between 300 and 1000 nm while at cryogenic temperatures, (P740(+)A(1)(-)
      P740A(1)) and ((3)P740-P740) absorbance difference spectra have been measured.
      Spectroscopic and kinetic evidence is presented that the cofactors involved in
      the electron transfer from the reduced secondary electron acceptor, phylloquinone
      (A(1)(-)), to the terminal electron acceptor and their structural arrangement are
      virtually identical to those of chlorophyll a containing photosystem I. The
      oxidation potential of the primary electron donor P740 of photosystem I has been
      reinvestigated. We find a midpoint potential of 450+/-10 mV in photosystem I
      enriched membrane fractions as well as in thylakoids which is very similar to
      that found for P700 in chlorophyll a dominated organisms. In addition, the
      extinction difference coefficient for the oxidation of the primary donor has been
      determined and a value of 45,000+/-4000 M(-1) cm(-1) at 740 nm was obtained.
      Based on this value the ratio of P740 to chlorophyll is calculated to be 1 : to
      approximately 200 chlorophyll d in thylakoid membranes. The consequences of our
      findings for the energetics in photosystem I of A. marina are discussed as well
      as the pigment stoichiometry and spectral characteristics of P740.

PMID- 18817747
TI  - Identifying the binding site(s) for antidepressants on the Torpedo nicotinic
      acetylcholine receptor: [3H]2-azidoimipramine photolabeling and molecular
      dynamics studies.
AB  - Radioligand binding, photoaffinity labeling, and docking and molecular dynamics
      were used to characterize the tricyclic antidepressant (TCA) binding sites in the
      nicotinic acetylcholine receptor (nAChR). Competition experiments indicate that
      the noncompetitive antagonist phencyclidine (PCP) inhibits [3H]imipramine binding
      to resting (closed) and desensitized nAChRs. [3H]2-azidoimipramine
      photoincorporates into each subunit from the desensitized nAChR with
      approximately 25% of the labeling specifically inhibited by TCP (a PCP analog),
      whereas no TCP-inhibitable labeling was observed in the resting (closed) state.
      For the desensitized nAChR and within the alpha subunit, the majority of specific
      [3H]2-azidoimipramine labeling mapped to a approximately 20 kDa Staphylococcus
      aureus V8 protease fragment (alphaV8-20; Ser173-Glu338). To further map the
      labeling site, the alphaV8-20 fragment was further digested with endoproteinase
      Lys-C and resolved by Tricine SDS-PAGE. The principal labeled fragment (11 kDa)
      was further purified by rpHPLC and subjected to N-terminal sequencing. Based on
      the amino terminus (alphaMet243) and apparent molecular weight, the 11 kDa
      fragment contains the channel lining M2 segment. Finally, docking and molecular
      dynamics results indicate that imipramine and PCP interact preferably with the M2
      transmembrane segments in the middle of the ion channel. Collectively, these
      results are consistent with a model where PCP and TCA bind to overlapping sites
      within the lumen of the Torpedo nAChR ion channel.

PMID- 18817748
TI  - Atom-scale molecular interactions in lipid raft mixtures.
AB  - We review the relationship between molecular interactions and the properties of
      lipid environments. A specific focus is given on bilayers which contain
      sphingomyelin (SM) and sterols due to their essential role for the formation of
      lipid rafts. The discussion is based on recent atom-scale molecular dynamics
      simulations, complemented by extensive comparison to experimental data. The
      discussion is divided into four sections. The first part investigates the
      properties of one-component SM bilayers and compares them to bilayers with
      phosphatidylcholine (PC), the focus being on a detailed analysis of the hydrogen
      bonding network in the two bilayers. The second part deals with binary mixtures
      of sterols with either SM or PC. The results show how the membrane properties may
      vary substantially depending on the sterol and SM type available, the membrane
      order and interdigitation being just two of the many examples of this issue. The
      third part concentrates on the specificity of intermolecular interactions in
      three-component mixtures of SM, PC and cholesterol (CHOL) under conditions where
      the concentrations of SM and CHOL are dilute with respect to that of PC. The
      results show how SM and CHOL favor one another, thus acting as nucleation sites
      for the formation of highly ordered nanosized domains. Finally, the fourth part
      discusses the large-scale properties of raft-like membrane environments and
      compares them to the properties of non-raft membranes. The differences turn out
      to be substantial. As a particularly intriguing example of this, the lateral
      pressure profiles of raft-like and non-raft systems indicate that the lipid
      composition of membrane domains may have a major impact on membrane protein
      activation.

PMID- 18817749
TI  - PCFT/SLC46A1 promoter methylation and restoration of gene expression in human
      leukemia cells.
AB  - The proton-coupled folate transporter (PCFT/SLC46A1) displays optimal and
      prominent folate and antifolate transport activity at acidic pH in human
      carcinoma cells but poor activity in leukemia cells. Consistently herein, human
      leukemia cell lines expressed poor PCFT transcript levels, whereas various
      carcinoma cell lines showed substantial PCFT gene expression. We identified a CpG
      island with high density at nucleotides -200 through +100 and explored its role
      in PCFT promoter silencing. Leukemia cells with barely detectable PCFT
      transcripts consistently harbored 85-100% methylation of this CpG island, whereas
      no methylation was found in carcinoma cells. Treatment with 5-Aza-2'
      deoxycytidine which induced demethylation but not with the histone deacetylase
      inhibitor trichostatin A, restored 50-fold PCFT expression only in leukemia
      cells. These findings constitute the first demonstration of the dominant
      epigenetic silencing of the PCFT gene in leukemia cells. The potential
      translational implications of the restoration of PCFT expression in chemotherapy
      of leukemia are discussed.

PMID- 18817750
TI  - Identification of Fructose-1,6-bisphosphate aldolase cytosolic class I as an NMH7
      MADS domain associated protein.
AB  - We are interested in identifying proteins that interact with the MADS domain
      protein NMH7 of Medicago sativa. We use an affinity column with a synthetic
      peptide derived from the MADS domain of NMH7 which has been reported to mediate
      protein-protein interaction with non-MADS domain interacting proteins. We
      identified approximately 40 and approximately 80kDa specifically bound proteins
      as the monomeric and dimeric forms of Fructose-1,6-bisphosphate aldolase
      cytosolic class I. NiNTA pull down assays revealed that K- and C-terminus regions
      of NMH7 are not required for the interaction with aldolase. Aldolase enzymatic
      activity is not required for the interaction with NMH7. NMH7 and aldolase were
      coimmunoprecipitated from non-inoculated seed and seedlings extracts.
      Colocalization studies using confocal microscopy showed that aldolase and NMH7
      are localized in the cytoplasm and the nucleus of the cortical cells. These data
      together show that M. sativa aldolase is a novel MADS domain binding protein, and
      suggest a broader functional repertory for this enzyme, as has been proposed for
      other glycolytic enzymes.

PMID- 18817751
TI  - Control of the blue fluorescent protein with advanced evolutionary pulse shaping.
AB  - We demonstrate optical coherent control of the two-photon fluorescence of the
      blue fluorescent protein (BFP), which is of interest in investigations of protein
      protein interactions. In addition to biological relevance, BFP represents an
      interesting target for coherent control from a chemical perspective due to its
      many components of highly nonexponential fluorescence decay and low quantum yield
      resulting from excited state isomerization. Using a genetic algorithm with a
      multiplicative (rather than ratiometric) fitness parameter, we are able to
      control the ratio of BFP fluorescence to second-harmonic generation without a
      considerable drop in the maximized signal. The importance of linear chirp and
      power-scaling on the discrimination process is investigated in detail.

PMID- 18817752
TI  - The powerful cardioprotective effects of urocortin and the corticotropin
      releasing hormone (CRH) family.
AB  - The urocortins are members of the corticotropin releasing hormone (CRH) family of
      peptide hormones. The archetypal member of this family, CRH, plays an important
      role in regulating thermogenesis and homeostasis by acting centrally and
      systemically in target organs via its two receptors CRH-R1 and CRH-R2. However,
      by virtue of their much greater relative affinity for CRH-R2, the physiological
      effects of the urocortin peptides are largely restricted to peripheral organs
      such as the heart. A powerful cytoprotective effect of urocortin peptide
      administration against ischemia and reperfusion injury has been demonstrated in
      isolated cardiomyocyte models, as well as in the intact heart both in vitro and
      in vivo. Extremely promising data has shown the beneficial effect of treating
      pacing-induced heart failure in sheep with urocortin molecules. Though the
      efficacy and specificity of these molecules in humans is not yet established,
      molecular dissection of the cytoprotective pathways activated by urocortin
      peptides suggests that the beneficial effects may be separable from potentially
      deleterious effects.

PMID- 18817754
TI  - Brain damage related to hemorrhagic transformation following cerebral ischemia
      and the role of K ATP channels.
AB  - BACKGROUND: Hemorrhagic transformation (HT) is a major factor limiting the use of
      thrombolytic treatment for stroke. Animal model can help us to understand HT.
      This study is to establish a HT model in rats to compare HT with uncomplicated
      cerebral infarction in neurobehavioral deficit, brain edema, brain adenosine
      triphosphatase (ATPase) activity and succinic dehydrogenase (SDH) activity, and
      to investigate its pathology changes as well as the impact of, Glibenclamide, a
      ATP-sensitive K(+) channel (K(ATP) channel) blocker, on the pathogenesis of HT.
      METHODS: Male, Sprague-Dawley rats were randomly assigned to four groups:
      hemorrhagic transformation (HT), cerebral infarction (CI), Glibenclamide+HT (GH)
      and a control. To create HT model, right middle cerebral artery occlusion (MCAO)
      was conducted with intraluminal thread technique; 30 min after MCAO, 50 microL
      arterial blood was injected into the caudate nucleus where the infarction
      occurred. Neurologic deficit was evaluated by Longa test, Berderson test and Beam
      test. Brain water content, brain ATPase activity and SDH activity were measured.
      Histology was examined using light microscope and transmission electron
      microscope. RESULTS: No significant difference in neurobehavioral deficit and
      brain water content was observed between HT and CI groups in all time points
      (P>0.05). Brain ATPase activity 12 h and 24 h after operation and brain SDH
      activity 24 h after the operation in HT group were both significantly increased
      compared with those in CI group (P<0.05); the increase of brain ATPase and SDH
      activity in HT group could be prevented by Glibenclamide. Neuronal degeneration
      and tissue edema in HT group, swollen neuropil and loosen intercellular substance
      in CI group were revealed by histology study. Ultrastructural changes including
      swollen mitochondria and interstitial edema were also observed in both HT and CI
      groups. CONCLUSIONS: The results demonstrated that moderate hemorrhagic
      transformation does not significantly aggravate cerebral infarction, and that
      K(ATP) channels have an important role in energy metabolism.

PMID- 18817753
TI  - The aryl hydrocarbon receptor cross-talks with multiple signal transduction
      pathways.
AB  - Exposure to toxic polycyclic aromatic hydrocarbons raises a number of toxic and
      carcinogenic responses in experimental animals and humans mediated for the most
      part by the aryl hydrocarbon -- or dioxin -- receptor (AHR). The AHR is a ligand
      activated transcription factor whose central role in the induction of drug
      metabolizing enzymes has long been recognized. For quite some time now, it has
      become clear that the AHR also functions in pathways outside of its role in
      detoxification and that perturbation of these pathways by xenobiotic ligands may
      be an important part of the toxicity of these compounds. AHR activation by some
      of its ligands participates among others in pathways critical to cell cycle
      regulation, mitogen-activated protein kinase cascades, immediate-early gene
      induction, cross-talk within the RB/E2F axis and mobilization of crucial calcium
      stores. Ultimately, the effect of a particular AHR ligand may depend as much on
      the adaptive interactions that it established with pathways and proteins
      expressed in a specific cell or tissue as on the toxic responses that it raises.

PMID- 18817755
TI  - Behavioral and respiratory characteristics during sleep in neonatal DBA/2J and
      A/J mice.
AB  - The ventilatory response to hypoxia depends on the carotid body function and
      sleep-wake states. Therefore, the response must be measured in a consistent sleep
      wake state. In mice, EMG with behavioral indices (coordinated movements, CMs;
      myoclonic twitches, MTs) has been used to assess sleep-wake states. However, in
      neonatal mice EMG instrumentation could induce stress, altering their behavior
      and ventilation. Accordingly, we examined: (1) if EMG can be eliminated for
      assessing sleep-wake states; and (2) behavioral characteristics and carotid body
      mediated respiratory control during sleep with EMG (EMG+) or without EMG (EMG-).
      Seven-day-old DBA/2J and A/J mice were divided into EMG+ and EMG- groups. In both
      strains, CMs occurred when EMG was high; MTs were present during silent/low EMG
      activity. The durations of high EMG activity and of CMs were statistically
      indifferent. Thus, CMs can be used to indicate wake state without EMG. The stress
      caused by EMG instrumentation may be distinctively manifested based on genetic
      background. Prolonged agitation was observed in some EMG+ DBA/2J (5 of 13), but
      not in A/J mice. The sleep time and MT counts were indifferent between the groups
      in DBA/2J mice. The EMG+ A/J group showed longer sleep time and less MT counts
      than the EMG- A/J group. Mean respiratory variables (baseline, hyperoxic/hypoxic
      responses) were not severely influenced by EMG+ in either strain. Individual
      values were more variable in EMG+ mice. Carotid body-mediated respiratory
      responses (decreased ventilation upon hyperoxia and increased ventilation upon
      mild hypoxia) during sleep were clearly observed in these neonatal mice with or
      without EMG instrumentation.

PMID- 18817756
TI  - Astroglial dye-coupling: an in vitro analysis of regional and interspecies
      differences in rodents and primates.
AB  - A regional and interspecies comparative analysis of astroglial coupling was
      performed using astroglia-enriched subcultures, following Lucifer Yellow dye
      intracellular injections. Rat cerebral cortex subcultures showed a greater
      coupling level than striatal subcultures. Interspecies analysis demonstrated a
      significant difference in the level of astroglial coupling in human cerebral
      cortex, compared with that of rat or monkey. Results provide an ex vivo insight
      into brain regional and interspecies differences of astroglial coupling, which
      may be associated with in situ modular or conditional cellular assemblies of the
      brain neuropil.

PMID- 18817757
TI  - Similar behaviour and primate-like properties of adult canine Schwann cells and
      olfactory ensheathing cells in long-term culture.
AB  - Adult canine Schwann cells and olfactory ensheathing cells (OECs) have been shown
      to promote neural regeneration in vivo. Since the majority of studies have been
      performed in rodents, it is not yet clear in how far OECs from large animals and
      humans share the reported properties. Moreover, due to the lack of comparative
      studies, it remains to be established whether Schwann cells and OECs display cell
      type-specific characteristics. In the present study, adult canine Schwann cells
      and OECs were comparatively analyzed regarding long-term growth, morphology,
      growth factor responsiveness, and antigenic expression. Adult canine Schwann
      cells and OECs displayed the same typical spindle-shaped morphology and expressed
      the cell type-specific marker p75(NTR). Moreover, the proliferation of both cell
      types was promoted by the same mitogens, including fibroblast growth factor-2
      (FGF-2) and heregulin-1beta (HRG-1beta). Several observations indicate that
      canine OECs differ from the well characterized rodent OECs and display properties
      reminiscent on primate cells. Both cell types (i) proliferated through multiple
      passages in the absence of growth factors and did not enter a senescent state
      until 3 months in culture, (ii) were not responsive to the cAMP-elevating agent
      forskolin, and (iii) stably expressed p75(NTR) in long-term culture. Taken
      together, this is the first report demonstrating that adult canine Schwann cells
      and OECs in long-term culture share the same in vitro characteristics and display
      primate-like properties. This underscores the relevance of the dog as a
      translational species between rodents and humans.

PMID- 18817758
TI  - Cholinergic signal transduction in the mouse sphenopalatine ganglion.
AB  - The sphenopalatine ganglia (SPG) receive their preganglionic innervation from the
      ventro-lateral reticular formation and nuclei of the caudal pons, and are
      involved in parasympathetic control of cranial glandular and vascular components
      including the blood supply to specific brain areas. In 53% of all SPG neurons, a
      particular member (MOL2.3) of the odorant receptor superfamily is co-expressed
      with green fluorescent protein (GFP) in MOL2.3 transgenic mouse pups. Choline
      acetyltransferase and vesicular acetylcholine transporter (VAChT) could be
      demonstrated in 90% of the GFP-positive, and 60% of the GFP-negative cells, these
      cells thus representing cholinergic neurons. Some 50% of all SPG neurons were
      nitrergic at a high rate of VAChT co-expression, the majority of them being GFP
      positive. Most SPG neurons received cholinergic innervation as demonstrated by
      perineuronal VAChT immunoreactive nerve terminals. To characterize cholinergic
      signal transduction in SPG neurons, calcium imaging experiments were performed in
      a SPG primary culture system containing GFP-positive and -negative neurons.
      Ganglionic neurons could repeatedly be activated by cholinergic stimulation in a
      dose-dependent manner, with calcium entering all cells from the extracellular
      compartment. Stimulation with specific agonists supported prevalence of nicotinic
      cholinergic receptors (nAChRs). Inhibition of cholinergically induced
      intracellular calcium signalling by various omega-conotoxins indicated functional
      expression of alpha 3 beta 4 and alpha 7 nAChR subtypes in murine SPG cells,
      which could be supported by RT-PCR analysis of the neonatal mouse SPG. With
      regard to secondary cholinergic activation, L- but not N-subtype voltage-gated
      calcium channels might represent a prime target. Nicotinic signal transduction
      did not prove to be different in GFP-positive as compared to-negative murine SPG
      neurons.

PMID- 18817759
TI  - Topography in the projections of lateral posterior thalamus with cingulate and
      medial agranular cortex in relation to circuitry for directed attention and
      neglect.
AB  - In the rat, the lateral posterior thalamic nucleus (LP) has reciprocal
      connections with areas of the cortex and the striatum involved in directed
      attention and its dysfunctional counterpart, contralateral neglect. It has also
      been shown that the medial portion of the mediorostral part of LP (mLPMR) is of
      special interest because it has connections with the dorsocentral striatum, a key
      node in this circuitry. In the present study we used neuroanatomical tracers to
      map the specific connections and topography of LP with the anterior cingulate
      cortex (ACC) and medial agranular cortex (AGm). We primarily used Alexa Fluor
      conjugates of the retrograde tracer cholera toxin subunit B, and injected two
      different colored conjugates into ACC and AGm in the same animal in order to
      directly compare the differential topography of the thalamocortical connections
      of mLPMR. The bidirectional tracer, dextran amine, was also used to examine
      anterograde corticothalamic projections of AGm and ACC. We found that mLPMR
      consists of two distinct groups of neurons, with the more dorsal group projecting
      to ACC and the more ventral group projecting to AGm. This is mirrored by a
      similar corticothalamic topography. These findings suggest that the ventral mLPMR
      is specifically associated with AGm and dorsocentral striatum, while dorsal mLPMR
      is associated with ACC. They also suggest that ACC may play a role in the
      circuitry for directed attention and contralateral neglect, as it is known to do
      in humans.

PMID- 18817760
TI  - Retinal projections to the thalamic paraventricular nucleus in the rock cavy
      (Kerodon rupestris).
AB  - The thalamic paraventricular nucleus (PVT) receives afferents from numerous brain
      areas, including the hypothalamic suprachiasmatic nucleus (SCN), considered to be
      the major circadian pacemaker. The PVT also sends projections to the SCN, limbic
      system centers and some nuclei involved in the control of the Sleep-Wake cycle.
      In this study, we report the identification of a hitherto not reported direct
      retinal projection to the PVT of the rock cavy, a typical rodent species of the
      northeast region of Brazil. After unilateral intravitreal injections of cholera
      toxin subunit B (CTb), anterogradely transported CTb-immunoreactive fibers and
      presumptive terminals were seen in the PVT. Some possible functional correlates
      of the present data are briefly discussed, including the role of the PVT in the
      modulation of the circadian rhythms by considering the reciprocal connections
      between the PVT and the SCN. The present work is the first to show a direct
      retinal projection to the PVT of a rodent and may contribute to elucidate the
      anatomical substrate of the functionally demonstrated involvement of this midline
      thalamic nucleus in the modulation of the circadian timing system.

PMID- 18817761
TI  - Maternal profiling of corticotropin-releasing factor receptor 2 deficient mice in
      association with restraint stress.
AB  - Mice deficient in corticotropin-releasing factor receptor 2 (CRF2)
      (C57BL/6J:129Sv background) exhibit impaired maternal defense (protection of
      offspring) and are more reactive to stressors than wild-type mice. To further
      understand CRF2's role in maternal behavior, we crossed the knockout mice with a
      line bred for high maternal defense that also has elevated maternal care relative
      to inbred lines. Maternal care was normal in knockout mice (relative to wild
      type). Maternal defense was impaired as previously observed. Exposure to a mild
      stressor (15 min restraint) did not trigger deficits in maternal defense in
      either genotype as determined by a two-way repeated measures ANOVA analysis.
      However, when examining difference scores between unrestrained and restrained
      conditions, knockout mice exhibited significant decreases in maternal defense
      with stress, suggesting knockouts are more susceptible to a mild stressor's
      effects. To gain possible insights into brain activity differences between WT and
      KO mice, we examined c-Fos expression in association with stress. Unrestrained KO
      mice exhibited significantly lower c-Fos levels relative to unrestrained WT mice
      in 9 regions, including lateral septum and periaqueductal gray. For WT mice,
      restraint stress triggered c-Fos activity increases in 3 regions while for KO
      mice, restraint stress triggered c-Fos increases in 16 regions. Taken together,
      our results suggest both altered behavioral and c-Fos responses to stress in
      lactating CRF2 KO mice.

PMID- 18817762
TI  - Semi-quantitative analysis of alpha-synuclein in subcellular pools of rat brain
      neurons: an immunogold electron microscopic study using a C-terminal specific
      monoclonal antibody.
AB  - Alpha-synuclein (alpha-Syn) is a brain-enriched protein of 140 amino acids.
      Despite of strong evidence showing the implication of the protein in the
      pathogenesis of several neurodegenerative diseases, its physiological function
      remains poorly understood. To study the physiological function of alpha-Syn, a
      depiction of its precise subcellular localization is necessary. Although alpha
      Syn expression in the brain has been extensively investigated using several
      different antibodies, its precise subcellular localization in neurons remains
      elusive. In this study, immunogold electron microscopy with a newly produced 3D5
      monoclonal antibody recognizing the C-terminal 115-121 amino acids of alpha-Syn
      was used to examine its subcellular localization in rat brain neurons. In
      addition, the relative amount of the protein in different subcellular pools of
      the neurons in several brain regions was evaluated and compared. The results
      showed that alpha-Syn-positive gold particles were unevenly distributed in axons,
      presynaptic terminals, cytoplasm and nucleus in the neuron, with the density of
      gold particles being greater in presynaptic terminals and nucleus than in other
      subcellular pools. In the cytoplasmic region, relatively dense gold particles
      were seen in some mitochondria. In the same subcellular pools, the density of
      gold particles was varied among the neurons from different brain regions.
      Although the cortical neurons showed much higher density of gold particles in the
      presynaptic terminals and nuclei than in striatal, hippocampal and substantia
      nigral neurons, the density of gold particles in their mitochondria was much
      lower compared with the mitochondria of striatal, hippocampal and substantia
      nigral neurons. The relative high level of mitochondrial alpha-Syn in
      hippocampus, striatum and substantia nigral neurons may have special
      pathophysiological significance, which deserves further investigation.

PMID- 18817763
TI  - Proteomic analysis of brain protein expression levels in NF-kappabeta p50 -/-
      homozygous knockout mice.
AB  - The role of nuclear factor kappa B (NF-kappaB) in oxidative stress, and most
      recently in pro- and anti-apoptotic-related mechanistic pathways, has well been
      established. Because of the dual nature of NF-kappaB, the wide range of genes it
      regulates and the plethora of stimuli that activate it, various studies
      addressing the functional role of NF-kappaB proteins have resulted in a number of
      differing findings. The present study examined the effect of a stimulus-free
      environment on the frontal cortex of mice brain with the p50 subunit of NF-kappaB
      knocked out p50 (-/-). Homozygous p50 mice knockout (KO) and wild type (WT) were
      used, and at 7-9 weeks they were sacrificed and various brain regions dissected.
      We analyzed the levels of oxidation in the frontal cortex of both the p50 (-/-)
      and WT mice. There was a significant reduction in the levels of protein-bound 4
      hydroxynonenal (HNE) [a lipid peroxidation product], 3-nitrotyrosine (3NT), and
      protein carbonyls in the p50 (-/-) mice when compared to the WT. A proteomic
      profile analysis identified ATP synthase gamma chain, ubiquinol-cyt-C reductase,
      heat shock protein 10 (Hsp10), fructose bisphosphate aldolase C, and NADH
      ubiquinone oxidoreductase as proteins whose expressions were significantly
      increased in the p50 (-/-) mice compared to the WT. With the reduction in the
      levels of oxidative stress and the increase in expression of key proteins in the
      p50 (-/-) brain, this study suggests that the p50 subunit can potentially be
      targeted for the development of therapeutic interventions in disorders in which
      oxidative stress plays a key role.

PMID- 18817764
TI  - Dysregulated CREB signaling pathway in the brain of neural cell adhesion molecule
      (NCAM)-deficient mice.
AB  - The neural cell adhesion molecule (NCAM) mediates cell-cell interactions and
      plays an important role in processes associated with neural plasticity, including
      learning and memory formation. It has been shown that mice deficient in all
      isoforms of NCAM (NCAM-/- mice) demonstrate impairment in long-term plasticity at
      multiple hippocampal synapses, disrupted spatial learning, and impaired
      contextual and auditory-cued fear conditioning. The formation of long-term memory
      is associated with activation of transcription factor CREB (cAMP response element
      binding protein). The aims of this study were to investigate NCAM-mediated
      signaling transduction pathways and the levels of the phosphorylated (Ser133)
      active form of the CREB in the brain structures (the pre- and frontal cortex,
      basolateral amygdala, and hippocampus) involved in the memory formation in NCAM
      deficient mice. Immunohistochemical analysis revealed reduced levels of pCREB in
      the prefrontal cortex (PFC), frontal cortex (FC), CA3 subregion of the
      hippocampus (CA3) and basolateral nucleus of amygdala (BLA) in NCAM-/- mice. NCAM
      /- mice had also reduced levels of the phosphorylated CaMKII and CaMKIV in PFC/FC
      and the hippocampus, which are the downstream signaling molecules of NCAM. The
      levels of non-phosphorylated kinases did not differ from those seen in the wild
      type mice. These results provide evidence that NCAM deficiency results in the
      dysregulation of CREB-mediated signaling pathways in the brain regions, which is
      related to the formation of memory.

PMID- 18817765
TI  - Contribution of NMDA receptor-mediated component to the EPSP in mouse Schaffer
      collateral synapses under single pulse stimulation protocol.
AB  - The degree to which NMDA receptors contribute to hippocampal CA(1) stratum
      radiatum excitatory postsynaptic potentials (EPSP) is a matter of debate. This
      experiment was designed to resolve the issue by documenting and positively
      identifying the elements of the NMDA dependent component in the extracellularly
      recorded stratum radiatum CA(1) field potential under low stimulation conditions
      and in the presence of physiologic levels of Mg(2+). We show that EPSP generation
      consists of activation of both AMPA and NMDA receptor channels, which mediate
      distinct components of the recorded field potential. We propose that the EPSP is
      a combination of two waves rather than one, which sometimes has been attributed
      to the exclusive activation of AMPA channels. Our data suggest that the three
      recorded peaks signify different events. The first peak reflects the presynaptic
      volley while the other two represent the actual EPSP. The first peak of the EPSP
      is determined mainly by flow of ions through AMPA channels. The second peak most
      likely is determined by the concurrence of two phenomena: ionic flow through NMDA
      channels and the source corresponding to the sink generated at the cell bodies in
      the pyramidal layer. The NMDA dependent component was recorded when Mg(2+) was
      present in physiological concentrations. The presynaptic volley and second peak
      do not saturate over a 10-fold increase of the stimulation charge and their
      amplitudes are highly correlated. The first peak amplitude rapidly saturates. The
      sensitivity of the recorded signals is different, the first peak being the most
      sensitive (1.25-0.26 mV/nC). Isolation of NMDA dependent components under
      physiological conditions when using a single pulse low stimulation protocol would
      allow more precise investigations of the NMDA dependent forms of synaptic
      plasticity.

PMID- 18817766
TI  - 13C-labeled mixed triglyceride breath test (13C MTG-BT) in healthy children and
      children with cystic fibrosis (CF) under pancreatic enzyme replacement therapy
      (PERT): a pilot study.
AB  - The MTG-BT estimates the hydrolysis of triacyl-glycerols by pancreatic lipase,
      and appears attractive for monitoring exogenous lipase requirements in patients
      with exocrine pancreatic insufficiency. To assess the test's discrimination
      capacity and repeatability, 9 CF patients with PERT and 10 healthy children
      underwent the (13)C-MTG-BT twice, at a 2- to 4-week interval. The test
      distinguished well between patients with severe exocrine pancreatic insufficiency
      (SEPI) and healthy subjects. However, within-subject variability for postprandial
      per thousand(13)C-enrichment and postprandial % dose recovery (PDR) was high in
      both groups. Therefore, the (13)C-MTG-BT seems useful to distinguish between SEPI
      and normal exocrine pancreatic function, but requires further development to
      improve its repeatability.

PMID- 18817767
TI  - Slit and Robo regulate dendrite branching and elongation of space-filling neurons
      in Drosophila.
AB  - Space-filling neurons extensively sample their receptive fields with fine
      dendritic branches. In this study we show that a member of the conserved Robo
      receptor family, Robo, and its ligand Slit regulate the dendritic differentiation
      of space-filling neurons. Loss of Robo or Slit function leads to faster
      elongating and less branched dendrites of the complex and space-filling class IV
      multi-dendritic dendrite-arborization (md-da) neurons in the Drosophila embryonic
      peripheral nervous system, but not of the simpler class I neurons. The total
      dendrite length of Class IV neurons is not modified in robo or slit mutant
      embryos. Robo mediates this process cell-autonomously. Upon Robo over-expression
      in md-da neurons the dendritic tree is simplified and time-lapse analysis during
      larval stages indicates that this is due to reduction in the number of newly
      formed branches. We propose that Slit, through Robo, provides an extrinsic signal
      to coordinate the growth rate and the branching level of space-filling neurons,
      thus allowing them to appropriately cover their target field.

PMID- 18817768
TI  - unc-3-dependent repression of specific motor neuron fates in Caenorhabditis
      elegans.
AB  - unc-3 encodes the Caenorhabditis elegans ortholog of the Olf-1/Early B cell
      factor family of transcription factors, which in vertebrates regulate development
      and differentiation of B lymphocytes, adipocytes, and cells of the nervous
      system. unc-3 mutants are uncoordinated in locomotion. Here we show that unc-3
      represses a VC-like motor neuron program in the VA and VB motor neurons, which in
      wild-type animals control backwards and forwards locomotion, respectively. We
      identify a physical interaction between UNC-3 and the C2H2 zinc finger
      transcription factor PAG-3, the mammalian homologs of which are coexpressed in
      olfactory epithelium and hematopoietic cells. Our data explain the locomotory
      defects of unc-3 mutants and suggest that interactions between unc-3 and pag-3
      orthologs in other species may be functionally important.

PMID- 18817769
TI  - Regulation of neurocoel morphogenesis by Pard6 gamma b.
AB  - The Par3/Par6/aPKC protein complex plays a key role in the establishment and
      maintenance of apicobasal polarity, a cellular characteristic essential for
      tissue and organ morphogenesis, differentiation and homeostasis. During a forward
      genetic screen for liver and pancreas mutants, we identified a pard6gammab
      mutant, representing the first known pard6 mutant in a vertebrate organism.
      pard6gammab mutants exhibit defects in epithelial tissue development as well as
      multiple lumens in the neural tube. Analyses of the cells lining the neural tube
      cavity, or neurocoel, in wildtype and pard6gammab mutant embryos show that lack
      of Pard6gammab function leads to defects in mitotic spindle orientation during
      neurulation. We also found that the PB1 (aPKC-binding) and CRIB (Cdc-42-binding)
      domains and the KPLG amino acid sequence within the PDZ domain (Pals1-and Crumbs
      binding) are not required for Pard6gammab localization but are essential for its
      function in neurocoel morphogenesis. Apical membranes are reduced, but not
      completely absent, in mutants lacking the zygotic, or both the maternal and
      zygotic, function of pard6gammab, leading us to examine the localization and
      function of the three additional zebrafish Pard6 proteins. We found that
      Pard6alpha, but not Pard6beta or Pard6gammaa, could partially rescue the
      pard6gammab(s441) mutant phenotypes. Altogether, these data indicate a previously
      unappreciated functional diversity and complexity within the vertebrate pard6
      gene family.

PMID- 18817770
TI  - Nuclear localization of Lyn tyrosine kinase mediated by inhibition of its kinase
      activity.
AB  - Src-family kinases, cytoplasmic enzymes that participate in various signaling
      events, are found at not only the plasma membrane but also subcellular
      compartments, such as the nucleus, the Golgi apparatus and late
      endosomes/lysosomes. Lyn, a member of the Src-family kinases, is known to play a
      role in DNA damage response and cell cycle control in the nucleus. However, it is
      still unclear how the localization of Lyn to the nucleus is regulated. Here, we
      investigated the mechanism of the distribution of Lyn between the cytoplasm and
      the nucleus in epitheloid HeLa cells and hematopoietic THP-1 cells. Lyn was
      definitely detected in purified nuclei by immunofluorescence and immunoblotting
      analyses. Nuclear accumulation of Lyn was enhanced upon treatment of cells with
      leptomycin B (LMB), an inhibitor of Crm1-mediated nuclear export. Moreover, Lyn
      mutants lacking the sites for lipid modification were highly accumulated in the
      nucleus upon LMB treatment. Intriguingly, inhibition of the kinase activity of
      Lyn by SU6656, Csk overexpression, or point mutation in the ATP-binding site
      induced an increase in nuclear Lyn levels. These results suggest that Lyn being
      imported into and rapidly exported from the nucleus preferentially accumulates in
      the nucleus by inhibition of the kinase activity and lipid modification.

PMID- 18817771
TI  - Cellular localization of the activated EGFR determines its effect on cell growth
      in MDA-MB-468 cells.
AB  - The epidermal growth factor (EGF) receptor (EGFR) is a ubiquitously expressed
      receptor tyrosine kinase that regulates diverse cell functions that are dependent
      upon cell type, the presence of downstream effectors, and receptor density. In
      addition to activating biochemical pathways, ligand stimulation causes the EGFR
      to enter the cell via clathrin-coated pits. Endocytic trafficking influences
      receptor signaling by controlling the duration of EGFR phosphorylation and
      coordinating the receptor's association with downstream effectors. To better
      understand the individual contributions of cell surface and cytosolic EGFRs on
      cell physiology, we used EGF that was conjugated to 900 nm polystyrene beads (EGF
      beads). EGF-beads can stimulate the EGFR and retain the activated receptor at the
      plasma membrane. In MDA-MB-468 cells, a breast cancer cell line that over
      expresses the EGFR, only internalized, activated EGFRs stimulate caspase-3 and
      induce cell death. Conversely, signaling cascades triggered from activated EGFR
      retained at the cell surface inhibit caspase-3 and promote cell proliferation.
      Thus, through endocytosis, the activated EGFR can differentially regulate cell
      growth in MDA-MB-468 cells.

PMID- 18817772
TI  - Tight junction protein ZO-2 expression and relative function of ZO-1 and ZO-2
      during mouse blastocyst formation.
AB  - Apicolateral tight junctions (TJs) between epithelial cells are multiprotein
      complexes regulating membrane polarity and paracellular transport and also
      contribute to signalling pathways affecting cell proliferation and gene
      expression. ZO-2 and other ZO family members form a sub-membranous scaffold for
      binding TJ constituents. We investigated ZO-2 contribution to TJ biogenesis and
      function during trophectoderm epithelium differentiation in mouse preimplantation
      embryos. Our data indicate that ZO-2 is expressed from maternal and embryonic
      genomes with maternal ZO-2 protein associated with nuclei in zygotes and
      particularly early cleavage stages. Embryonic ZO-2 assembled at outer blastomere
      apicolateral junctional sites from the late 16-cell stage. Junctional ZO-2 first
      co-localised with E-cadherin in a transient complex comprising adherens junction
      and TJ constituents before segregating to TJs after their separation from the
      blastocyst stage (32-cell onwards). ZO-2 siRNA microinjection into zygotes or 2
      cell embryos resulted in specific knockdown of ZO-2 mRNA and protein within
      blastocysts. Embryos lacking ZO-2 protein at trophectoderm TJs exhibited delayed
      blastocoel cavity formation but underwent normal cell proliferation and outgrowth
      morphogenesis. Quantitative analysis of trophectoderm TJs in ZO-2-deficient
      embryos revealed increased assembly of ZO-1 but not occludin, indicating ZO
      protein redundancy as a compensatory mechanism contributing to the mild phenotype
      observed. In contrast, ZO-1 knockdown, or combined ZO-1 and ZO-2 knockdown,
      generated a more severe inhibition of blastocoel formation indicating distinct
      roles for ZO proteins in blastocyst morphogenesis.

PMID- 18817773
TI  - D-Glucose sensing by a plasma membrane regulator of G signaling protein, AtRGS1.
AB  - Plants use sugars as signaling molecules and possess mechanisms to detect and
      respond to changes in sugar availability, ranging from the level of secondary
      signaling molecules to altered gene transcription. G-protein-coupled pathways are
      involved in sugar signaling in plants. The Arabidopsis thaliana regulator of G
      protein signaling protein 1 (AtRGS1) combines a receptor-like seven transmembrane
      domain with an RGS domain, interacts with the Arabidopsis Galpha subunit (AtGPA1)
      in a d-glucose-regulated manner, and stimulates AtGPA1 GTPase activity. We
      determined that AtRGS1 interacts with additional components, genetically defined
      here, to serve as a plasma membrane sensor for d-glucose. This interaction
      between AtRGS1 and AtGPA1 involves, in part, the seven-transmembrane domain of
      AtRGS1.

PMID- 18817774
TI  - Caught in the act: ATP hydrolysis of an ABC-multidrug transporter followed by
      real-time magic angle spinning NMR.
AB  - The ATP binding cassette (ABC) transporter LmrA from Lactococcus lactis
      transports cytotoxic molecules at the expense of ATP. Molecular and kinetic
      details of LmrA can be assessed by solid-state nuclear magnetic resonance
      (ssNMR), if functional reconstitution at a high protein-lipid ratio can be
      achieved and the kinetic rate constants are small enough. In order to follow ATP
      hydrolysis directly by 31P-magic angle spinning (MAS) nuclear magnetic resonance
      (NMR), we generated such conditions by reconstituting LmrA-dK388, a mutant with
      slower ATP turnover rate, at a protein-lipid ration of 1:150. By analysing time
      resolved 31P spectra, protein activity has been directly assessed. These data
      demonstrate the general possibility to perform ssNMR studies on a fully active
      full length ABC transporter and also form the foundation for further kinetic
      studies on LmrA by NMR.

PMID- 18817775
TI  - Taxol and 10-deacetylbaccatinIII induce distinct changes in the dynamics of
      caveolae.
AB  - Taxol treatment of HeLa cells resulted in a transient recruitment of Caveolin-1
      to the cell surface followed by internalization. Interestingly, 20min after 10
      deacetylbaccatinIII (10-DAB) treatment, the caveolae displayed faster 'kiss and
      run' dynamics while BaccatinIII (BacIII) did not induce any change. Sustained
      phosphorylation of Caveolin-1 is observed upon treatment and between Taxol and 10
      DAB, the former shows phosphorylated Raf-1, ERK1/2 and hyperphosphorylated Bcl-2
      while the later showed much less magnitude of the same. BacIII treatment did not
      induce phosphorylation of Raf-1 or Bcl-2. It is possible that Taxol might act on
      multiple targets and the side chain may be crucial.

PMID- 18817776
TI  - Vitamin E dependent microRNA regulation in rat liver.
AB  - Dietary vitamin E (VE) is known to regulate gene expression by altering mRNA
      concentrations. Recently, microRNA (miRNA) have been discovered as a means of
      posttranscriptional gene regulation. Since the effect of VE on miRNA regulation
      is unknown, we fed rats for 6 months diets deficient or sufficient in VE and
      determined hepatic concentrations of miRNA involved in processes previously
      associated with VE (lipid metabolism, miRNA-122a; cancer and inflammation, miRNA
      125b). VE-deficiency resulted in reduced concentrations of miRNA-122a and miRNA
      125b. The findings of the present study demonstrate that differences in dietary
      VE may affect hepatic miRNA concentrations in vivo.

PMID- 18817777
TI  - Air pollution induces enhanced mitochondrial oxidative stress in cystic fibrosis
      airway epithelium.
AB  - We studied the effects of airborne particulate matters (PM) on cystic fibrosis
      (CF) epithelium. We noted that PM enhanced human CF bronchial epithelial
      apoptosis, activated caspase-9 and PARP-1; and reduced mitochondrial membrane
      potential. Mitochondrial inhibitors (4,4-diisothiocyanatostilbene-2,2'disulfonic
      acid, rotenone and thenoyltrifluoroacetone) blocked PM-induced generation of
      reactive oxygen species and apoptosis. PM upregulated pro-apoptotic Bad, Bax, p53
      and p21; and enhanced mitochondrial localization of Bax. The anti-apoptotic Bcl
      2, Bcl-xl, Mcl-1 and Xiap remained unchanged; however, overexpression of Bcl-xl
      blocked PM-induced apoptosis. Accordingly, we provide the evidence that PM
      enhances oxidative stress and mitochondrial signaling mediated apoptosis via the
      modulation of Bcl family proteins in CF.

PMID- 18817778
TI  - The inhibition of female rabbit sexual behavior by progesterone: progesterone
      receptor-dependent and-independent effects.
AB  - In the pregnant domestic rabbit, scent marking ("chinning") and sexual behavior
      are inhibited by ovarian-derived progesterone (P). In order to distinguish
      behavioral effects of P that are PR-dependent from those mediated by its ring A
      reduced metabolites, we administered P, P+RU486 (PR antagonist), chlormadinone
      acetate (CA, synthetic progestin that does not form ring A reduced metabolites),
      or vehicle to ovariectomized (ovx) estradiol-benzoate (EB)-treated female
      rabbits, via sc injection, on experimental day 0. Chinning was quantified daily,
      and mating tests were done on days -1, 1, 3, 5, and 7. On day 1, chinning was
      significantly decreased, and the latency to be mounted by the male was
      significantly increased (indicating decreased sexual attractivity of the female)
      in P-treated females. The effect of P on chinning, but not its effect on sexual
      attractivity, was completely blocked by RU486 and replicated by CA. Although CA
      had no effect on attractivity on day 1, it decreased both sexual receptivity and
      attractivity on day 3. In a preference test in which the male could interact with
      either an ovx EB-treated female or an ovx female that had received one of the
      above hormone treatments 24 h earlier, P decreased sexual attractivity and
      increased aggression. The effect of P on aggression, but not its effect on
      attractivity, was blocked by RU486 and replicated by CA. These results indicate
      that both PR-dependent and PR-independent mechanisms decrease sexual
      attractivity, whereas PR activation is necessary for the inhibition of chinning
      and sexual receptivity, and for the stimulation of aggression.

PMID- 18817779
TI  - Typing of four genetic loci discriminates among closely related species of New
      World Leishmania.
AB  - All New World Leishmania species can cause cutaneous lesions, while only
      Leishmania (Viannia) braziliensis has been associated with mucosal metastases.
      Multilocus enzyme electrophoresis (MLEE) is the optimal standard for species
      identification but is slow and costly. New methods for species identification are
      needed to ensure proper identification and therapy. The coding regions of four
      metabolic enzyme markers in the MLEE typing method: mannose phosphate isomerase
      (MPI), malate dehydrogenase (MDH), glucose-6-phosphate isomerase (GPI), and 6
      phosphogluconate dehydrogenase (6PGD), were analysed from seven species of New
      World Leishmania isolated from patients with either cutaneous or mucosal lesions
      to identify specific genetic polymorphisms responsible for the phenotypic
      variations observed in the MLEE typing scheme. We identified species-specific
      polymorphisms and determined that a combination of sequencing of the mpi and 6pgd
      genes was sufficient to differentiate among seven closely related species of New
      World Leishmania and among isolates of L. braziliensis shown previously to have
      atypical MLEE patterns. When DNA isolated from 10 cutaneous lesion biopsies were
      evaluated, the sequence typing method was 100% concordant with the published
      MLEE/monoclonal antibody identification methods. The identification of species
      specific polymorphisms can be used to design a DNA-based test with greater
      discriminatory power that requires shorter identification times. When the
      causative agent of the disease is L. braziliensis, this method ensures correct
      species identification, even when the agent is a genetic variant. Proper
      identification could facilitate adequate treatment, preventing the onset of the
      disfiguring mucosal form of the disease.

PMID- 18817780
TI  - Decreased intercellular coupling improves the function of cardiac pacemakers
      derived from mouse embryonic stem cells.
AB  - The aim of this study was to determine if embryonic stem cell derived
      cardiomyocyte aggregates (ESdCs) can act as pacemakers in spontaneously active
      cardiomyocyte preparations when their connexin isoform expression is tuned toward
      a more sinus nodal phenotype. Using microelectrode array recordings (MEAs), we
      demonstrate that mouse ESdCs establish electrical coupling with spontaneously
      active cardiomyocyte preparations (HL-1 monolayer) and obtain pacemaker
      dominance. WT- and Cx43(-/-)-ESdCs comparably established intercellular coupling
      with cardiac host tissue (Cx43(-/-): 86% vs. WT: 91%). Although both aggregates
      had a 100% success rate in pacing quiescent cardiac preparations, Cx43(-/-)-ESdCs
      had an increased likelihood of gaining pacemaker dominance (Cx43(-/-): 40% vs.
      WT: 13%) in spontaneously active preparations. No differences in size, beating
      frequency, V(m), or differentiation were detected between WT- and Cx43(-/-)-ESdCs
      but the intercellular coupling resistance in Cx43(-/-)-ESdCs was significantly
      increased (Cx43(-/-): 1.2nS vs. WT: 14.8nS). Lack of Cx43 prolonged the time
      until Cx43(-/-)-ESdCs established frequency synchronization with the host tissue.
      It further hampered the excitation spread from the cardiomyocyte preparation into
      the ESdC. However rectifying excitation spread in these co-cultures could not be
      unequivocally identified. In summary, ESdCs can function as dominant biological
      pacemakers and Cx43 expression is not a prerequisite for their electrical
      integration. Maintenance of pacemaker dominance depends critically on the
      pacemaker's gap junction expression benefiting those with increased intercellular
      coupling resistances. Our results provide important insight into the design of
      biological pacemakers that will benefit the use of cardiomyocytes for cell
      replacement therapy.

PMID- 18817781
TI  - Insights into mechanisms linking cardiac hypertrophy and atrial fibrosis:
      evidence for a role of histone deacetylase in atrial fibrillation pathophysiology
      and therapy.

PMID- 18817782
TI  - H(2)O(2)-induced left ventricular dysfunction in isolated working rat hearts is
      independent of calcium accumulation.
AB  - Reactive oxygen species (ROS) and intracellular Ca(2+) overload play key roles in
      myocardial ischemia-reperfusion (IR) injury but the relationships among ROS,
      Ca(2+) overload and LV mechanical dysfunction remain unclear. We tested the
      hypothesis that H(2)O(2) impairs LV function by causing Ca(2+) overload by
      increasing late sodium current (I(Na)), similar to Sea Anemone Toxin II (ATX-II).
      Diastolic and systolic Ca(2+) concentrations (d[Ca(2+)](i) and s[Ca(2+)](i)) were
      measured by indo-1 fluorescence simultaneously with LV work in isolated working
      rat hearts. H(2)O(2) (100 microM, 30 min) increased d[Ca(2+)](i) and
      s[Ca(2+)](i). LV work increased transiently then declined to 32% of baseline
      before recovering to 70%. ATX-II (12 nM, 30 min) caused greater increases in
      d[Ca(2+)](i) and s[Ca(2+)](i). LV work increased transiently before declining
      gradually to 17%. Ouabain (80 microM) exerted similar effects to ATX-II. Late
      I(Na) inhibitors, lidocaine (10 microM) or R56865 (2 microM), reduced effects of
      ATX-II on [Ca(2+)](i) and LV function, but did not alter effects of H(2)O(2). The
      antioxidant, N-(2-mercaptopropionyl)glycine (MPG, 1 mM) prevented H(2)O(2)
      induced LV dysfunction, but did not alter [Ca(2+)](i). Paradoxically, further
      increases in [Ca(2+)](i) by ATX-II or ouabain, given 10 min after H(2)O(2),
      improved function. The failure of late I(Na) inhibitors to prevent H(2)O(2)
      induced LV dysfunction, and the ability of MPG to prevent H(2)O(2)-induced LV
      dysfunction independent of changes in [Ca(2+)](i) indicate that impaired
      contractility is not due to Ca(2+) overload. The ability of further increases in
      [Ca(2+)](i) to reverse H(2)O(2)-induced LV dysfunction suggests that Ca(2+)
      desensitization is the predominant mechanism of ROS-induced contractile
      dysfunction.

PMID- 18817783
TI  - Heart protection by ischemic preconditioning: a novel pathway initiated by iron
      and mediated by ferritin.
AB  - Ischemic preconditioning is a well-known procedure transiently protecting the
      heart against injury associated with prolonged ischemia, through mechanism/s only
      partly understood. The aim of this study was to test whether preconditioning
      induced protection of the heart involves an iron-based mechanism, including the
      generation of an iron signal followed by accumulation of ferritin. In isolated
      rat hearts perfused in the Langendorff configuration, we measured heart
      contractility, ferritin levels, ferritin-iron content, and mRNA levels of
      ferritin subunits. Ischemic preconditioning caused rapid accumulation of
      ferritin, reaching 359% of the baseline value (set at 100%). This was accompanied
      by a parallel decline in ferritin-bound iron: from 2191+/-548 down to 760+/-34 Fe
      atoms/ferritin molecule, p<0.05. Ferritin levels remained high during the
      subsequent period of prolonged ischemia, and returned to nearly the baseline
      value during the reperfusion phase. Selective iron chelators (acetyl hydroxamate
      or Zn-desferrioxamine) abrogated the functional protection and suppressed
      ferritin accumulation, thus demonstrating the essentiality of an iron signal in
      the preconditioning-induced protective mechanism. Moreover, introduction of an
      iron-containing ternary complex, known to import iron into cells, caused a three
      fold accumulation of ferritin and simulated the preconditioning-induced
      functional protection against prolonged myocardial ischemia. The ischemic
      preconditioning-and-ischemia-induced increase in ferritin levels correlated well
      with the accumulation of ferritin L-subunit mRNA: 5.44+/-0.47 vs 1.23+/-0.15
      (units) in the baseline, p<0.05, suggesting that transcriptional control of
      ferritin L-subunit synthesis had been activated. Ischemic preconditioning
      initiates de novo synthesis of ferritin in the heart; the extra ferritin is
      proposed to serve a 'sink' for redox-active iron, thus protecting the heart from
      iron-mediated oxidative damage associated with ischemia-reperfusion injury. The
      present results substantiate a novel iron-based mechanism of ischemic
      preconditioning and could pave the way for the development of new modalities of
      heart protection.

PMID- 18817784
TI  - Understanding the organisation and role of myosin binding protein C in normal
      striated muscle by comparison with MyBP-C knockout cardiac muscle.
AB  - Myosin binding protein C (MyBP-C) is a component of the thick filament of
      striated muscle. The importance of this protein is revealed by recent evidence
      that mutations in the cardiac gene are a major cause of familial hypertrophic
      cardiomyopathy. Here we investigate the distribution of MyBP-C in the A-bands of
      cardiac and skeletal muscles and compare this to the A-band structure in cardiac
      muscle of MyBP-C-deficient mice. We have used a novel averaging technique to
      obtain the axial density distribution of A-bands in electron micrographs of well
      preserved specimens. We show that cardiac and skeletal A-bands are very similar,
      with a length of 1.58+/-0.01 mum. In normal cardiac and skeletal muscle, the
      distributions are very similar, showing clearly the series of 11 prominent
      accessory protein stripes in each half of the A-band spaced axially at 43-nm
      intervals and starting at the edge of the bare zone. We show by antibody
      labelling that in cardiac muscle the distal nine stripes are the location of MyBP
      C. These stripes are considerably suppressed in the knockout mouse hearts as
      expected. Myosin heads on the surface of the thick filament in relaxed muscle are
      thought to be arranged in a three-stranded quasi-helix with a mean 14.3-nm axial
      cross bridge spacing and a 43 nm helix repeat. Extra "forbidden" meridional
      reflections, at orders of 43 nm, in X-ray diffraction patterns of muscle have
      been interpreted as due to an axial perturbation of some levels of myosin heads.
      However, in the MyBP-C-deficient hearts these extra meridional reflections are
      weak or absent, suggesting that they are due to MyBP-C itself or to MyBP-C in
      combination with a head perturbation brought about by the presence of MyBP-C.

PMID- 18817785
TI  - CHD1 assumes a central role during follicle development.
AB  - During Bombyx mori follicle development, fine-tuning of chorion gene expression
      is under the control of bidirectional promoters. In this work, we show that the
      silkmoth chromo-helicase/ATPase-DNA binding protein 1 (CHD1) ortholog is
      responsible for repositioning of nucleosomes on chorion promoters, where the
      factor binds specifically. Chorion genes, occupying a single chromosomal locus,
      rely on an almost identical set of cis elements for their differential
      expression. As a direct consequence of remodeling, interaction of C/EBP and TFIID
      with promoter elements is facilitated and ultimately leads to initiation of
      transcription. Appending of methylation marks to H3K4 in a temporal-specific
      manner is dependent on CHD1 binding to cognate cis elements and signifies gene
      activation. Overall, CHD1 is a critical factor for proper development of the
      follicular epithelium in terms of whole-cell chromatin arrangement.

PMID- 18817786
TI  - Structural changes in the muscle thin filament during contractions caused by
      single and double electrical pulses.
AB  - In order to investigate the structural changes of the myofilaments involved in
      the phenomenon of summation in skeletal muscle contraction, we studied small
      angle x-ray intensity changes during twitches of frog skeletal muscle elicited by
      either a single or a double stimulus at 16 degrees C. The separation of the
      pulses in the double-pulse stimulation was either 15 or 30 ms. The peak tension
      was more than doubled by the second stimulus. The equatorial (1,0) intensity,
      which decreased upon the first stimulus, further decreased with the second
      stimulus, indicating that more cross-bridges are formed. The meridional
      reflections from troponin at 1/38.5 and 1/19.2 nm(-1) were affected only slightly
      by the second stimulus, showing that attachment of a small number of myosin heads
      to actin can make a cooperative structural change. In overstretched muscle, the
      intensity increase of the troponin reflection in response to the second stimulus
      was smaller than that to the first stimulus. These results show that the
      summation is not due to an increased Ca binding to troponin and further suggest a
      highly cooperative nature of the structural changes in the thin filament that are
      related to the regulation of contraction.

PMID- 18817787
TI  - A generalized compartmental model to estimate the fibre mass in the
      ruminoreticulum: 2. Integrating digestion and passage.
AB  - Models used to predict digestibility and fill of the dietary insoluble fibre
      (NDF) treat the ruminoreticular particulate mass as a single pool. The underlying
      assumption is that escape of particles follows first-order kinetics. In this
      paper, we proposed and evaluated a model of two ruminoreticular sequential NDF
      pools. The first pool is formed by buoyant particles (raft pool) and the second
      one by fluid dispersed particles (escapable pool) ventrally to the raft. The
      transference of particles between these two pools results from several processes
      that reduce particles buoyancy, assuming the gamma distribution. The exit of
      escapable pool particles from the ruminoreticulum is exponentially distributed.
      These concepts were evaluated by comparing ruminoreticular NDF masses as 43 and
      27 means from cattle and sheep, respectively, to the same predicted variable
      using single- and two-pools models. Predictions of the single-pool model were
      based on lignin turnover and the turnover associated to the descending phase of
      the elimination of Yb-labelled forage particles in the faeces of sheep.
      Predictions of the two-pool model were obtained by estimating fractional passage
      rates associated to the ascending and descending phases of the same Yb excretion
      profiles in sheep faeces. All turnovers were scaled to the power 0.25 of body
      mass for interspecies comparisons. Predictions based on lignin turnover (single
      pool) and the two-pool model presented similar trends, accuracies and precisions.
      The single-pool approach based solely on the descending phase of the marker
      yielded biased estimates of the ruminoreticular NDF mass.

PMID- 18817788
TI  - Model-based identification and diagnosis of a porcine model of induced endotoxic
      shock with hemofiltration.
AB  - A previously validated cardiovascular system (CVS) model and parameter
      identification method for cardiac and circulatory disease states are extended and
      further validated in a porcine model (N=6) of induced endotoxic shock with
      hemofiltration. Errors for the identified model are within 10% when the model is
      re-simulated and compared to the clinical data. All identified parameter trends
      over time in the experiments match clinically expected changes both individually
      and over the cohort. This work represents a further clinical validation of these
      model-based cardiovascular diagnosis and therapy guidance methods for use with
      monitoring endotoxic disease states.

PMID- 18817789
TI  - Mechanism of the neuroprotective role of coenzyme Q10 with or without L-dopa in
      rotenone-induced parkinsonism.
AB  - Current treatment options for parkinsonism as a neurodegenerative disease are
      limited and still mainly symptomatic and lack significant disease-modifying
      effect. Understanding its molecular pathology and finding the cause of
      dopaminergic cell loss will lead to exploring therapies that could prevent and
      cure the disease. Mitochondrial dysfunction was found to stimulate releasing of
      reactive oxygen species (ROS) with subsequent induction of apoptotic neuronal
      cell death. The aim of the present study was to throw the light on the role of
      coenzyme Q10 with or without L-dopa in an experimental model of parkinsonism
      induced by rotenone in rats. The present work showed that rotenone (2.5 mg/kg/day
      i.p. for 60 days) induced a model of parkinsonism (group II) resembling the basic
      findings in human characterized by bradykinesia and rigidity manifested as an
      increase in catalepsy score (detected after 20 days with bad prognosis after 60
      days) with marked decrease in striatal dopamine levels. This model confirmed the
      implication of mitochondrial-apoptotic pathway in the pathogenesis of
      parkinsonism as there was a decrease in levels of striatal complex I activity and
      ATP as well as extreme overexpression of the antiapoptotic protein Bcl-2, and
      also exhibited the role of coenzyme Q10 where its plasma and striatal levels were
      found to be decreased in comparison to the normal control rats (group I). This
      proposed pathogenesis was evidenced by the significant correlation between
      catalepsy score and the neurochemical parameters obtained in the current work.
      The treated groups started to receive the drug(s) after 20 days from induction of
      parkinsonism and continued to complete for 60 days. Oral administration of Co Q10
      in a low dose 200 mg/kg/day (group III) or a high dose 600 mg/kg/day (group IV),
      resulted in amelioration of the mitochondrial induced apoptosis by dose-dependent
      restoration of striatal complex I activity, ATP levels with temperate increase in
      expression of Bcl-2 as well as decrease in catalepsy score. Although both low and
      high doses of Co Q10 resulted in significant increase in its plasma and striatal
      levels, but only the high dose was shown to reach the recommended therapeutic
      levels. As a current replacement therapy, oral administration of levodopa 10
      mg/kg/day (group V), caused symptomatic improvement in the form of reduction of
      catalepsy score with restoration of striatal dopamine levels, but it did not show
      any significant effects on either striatal complex I activity, ATP levels or the
      expression of Bcl-2, pointing to the lack of its disease-modifying role. On the
      other hand, its administration with high dose of coenzyme Q10 caused the most
      marked symptomatic improvement in catalepsy score when compared to its
      administration with low dose of coenzyme Q10, or when compared to either coenzyme
      Q10 high dose or L-dopa, respectively. Moreover, administration of high dose
      coenzyme Q10 with L-dopa provided a significant increase in striatal complex I
      activity, ATP levels and Bcl-2 expression in comparison to group administered
      coenzyme Q10 low dose with L-dopa, in addition to the significant restoration of
      striatal dopamine levels and both plasma and striatal Co Q10 levels. Regarding
      that L-dopa is viewed as a replacement therapy in parkinsonism, it could be
      concluded that addition of coenzyme Q10 in a high dose in early parkinson's
      disease could be recommended based on its proved disease-modifying role on
      several levels of the proposed mechanisms, including improvement of respiratory
      chain activity and intervention with neuronal apoptosis. A further research to
      investigate other apoptosis-targeted compounds will open a new era in the
      treatment of parkinsonism.

PMID- 18817790
TI  - Ligand gated ion channels.

PMID- 18817791
TI  - FMRI signals associated with memory strength in the medial temporal lobes: a meta
      analysis.
AB  - To identify patterns of memory-related neural activity in the medial temporal
      lobes (MTL), a quantitative meta-analysis of 17 functional magnetic resonance
      imaging (fMRI) studies was performed. The analysis shows that increased activity
      in the hippocampus and the parahippocampal cortex predicts subsequent memory
      strength. During retrieval, activity in the hippocampus increases in association
      with strong memory. In the perirhinal cortex, increased activity predicts
      subsequent recognition, whether based on weak or strong memory, whereas during
      retrieval activity decreases below the level for misses in association with both
      weak and strong memory. The results are consistent with the claim that the
      hippocampus selectively subserves recollection, whereas adjacent structures
      subserve familiarity [Eichenbaum, H., Yonelinas, A., & Ranganath, C. (2007). The
      medial temporal lobe and recognition memory. The Annual Review of Neuroscience,
      30, 123-152]. However, this conclusion depends on a specific dual-process theory
      of recognition memory that has been used to interpret the results. An alternative
      dual-process model holds that the behavioral methods used to differentiate
      recollection from familiarity instead separate strong memories from weak
      memories. When the fMRI data are interpreted in terms of the alternative theory,
      the fMRI results do not point to selective roles for the hippocampus or the
      adjacent MTL structures. The fMRI data alone cannot distinguish between these two
      models, so other methods are needed to resolve the issue.

PMID- 18817792
TI  - Left and right memory revisited: electrophysiological investigations of
      hemispheric asymmetries at retrieval.
AB  - Hemispheric differences in the use of memory retrieval cues were examined in a
      continuous recognition design, using visual half-field presentation to bias the
      processing of test words. A speeded recognition task revealed general accuracy
      and response time advantages for items whose test presentation was biased to the
      left hemisphere. A second experiment recorded event-related brain potentials in
      the same design and replicated these behavioral effects, but found no
      electrophysiological support for the hypothesis that test words biased to the
      left hemisphere elicit superior recognition. Instead, successful retrieval was
      accompanied by memory components of identical strength regardless of test field.
      That robust visual field effects in response accuracy and speed were not mimicked
      in memory components that generally do correlate with such behavioral differences
      suggests that patterns in overt responses may be dominated by the left
      hemisphere's superior ability to apprehend words. Differences between the data
      pattern observed in the present study with lateralized retrieval and that in a
      prior study with lateralized encoding [Evans, K. M., & Federmeier, K. D. (2007).
      The memory that's right and the memory that's left: Event-related potentials
      reveal hemispheric asymmetries in the encoding and retention of verbal
      information. Neuropsychologia 45(8), 1777-1790.] support the notion that
      hemispheric processing is highly integrated in the intact brain, and highlight
      the need to treat lateralization at different stages as distinct.

PMID- 18817793
TI  - Visual extinction: the effect of temporal and spatial bias.
AB  - Unlike patients with neglect, neurological patients with extinction can detect a
      single event presented at any location. However, when shown two brief near
      simultaneous stimuli they only report the ipsilesional item. The question of what
      inter-stimulus delay leads to maximal extinction has clear clinical and
      theoretical implications. di Pellegrino et al. [di Pellegrino, G., Basso, G., &
      Frassinetti, F. (1997). Spatial extinction on double asynchronous stimulation.
      Neuropsychologia, 35, 1215-1223] report that extinction is maximal when the two
      stimuli are presented simultaneously, with less extinction when either item has a
      slight temporal lead. This finding supports traditional clinical diagnosis (which
      only presents simultaneous events), and is in accord with theories of extinction
      that entail individuation of objects (e.g. "token" accounts). In contrast, Cate
      and Behrmann [Cate, A., & Behrmann, M. (2002). Spatial and temporal influences of
      extinction. Neuropsychologia, 40, 2206-2225] report that extinction is maximal
      when the ipsilesional item is presented slightly prior to the contralesional
      item. This finding appears to support disengage models of attention. Our aim was
      to reveal whether the difference between these studies reflects different
      patients, or different methods. Specifically, we note that the stimuli used by
      Cate and Behrmann were biased both temporally (more ipsilesional first trials)
      and spatially (more items presented in ipsilesional field). We examined the
      performance of nine individuals with extinction, and found that maximal
      extinction was not influenced by temporal biases, but extinction was modulated by
      the spatial location of stimuli. This finding reconciles previous studies and
      offers new insight into this syndrome.

PMID- 18817794
TI  - Is hyper-aggressiveness associated with physiological hypoarousal? A comparative
      study on mouse lines selected for high and low aggressiveness.
AB  - Aggressiveness is often considered a life-long, persistent personality trait and
      is therefore expected to have a consistent neurobiological basis. Recent meta
      analyses on physiological correlates of aggression and violence suggest that
      certain aggression-related psychopathologies are associated with low functioning
      of the hypothalamo-pituitary-adrenal (HPA) axis and autonomic nervous system
      (ANS). We tested this hypothesis in mice selected for high and low aggressiveness
      by measuring baseline plasma corticosterone levels and, via radiotelemetry, heart
      rate and core body temperature. The radiotelemetric recordings were made for 48 h
      under baseline undisturbed conditions and for 90 min after a handling stressor.
      Consistent with the hypoarousal hypothesis of violence, we found lower resting
      heart rates in two out of the three highly aggressive selection lines. In
      contrast, body temperature during the active phase, as another ANS-regulated
      physiological parameter, was higher in two out of three highly aggressive lines.
      The handling-induced tachycardiac and hyperthermic responses were similar across
      the six mouse lines except for the most docile and obese line, which showed a
      blunted reactivity. Besides significant differences between strains, no
      differences in plasma corticosterone levels were found between the high- and low
      aggressive phenotypes. These results are discussed in relation to the different
      types of aggression (normal versus pathological) exhibited by the three highly
      aggressive lines. We conclude that while high trait-like aggressiveness is
      generally associated with a higher active phase core body temperature, only
      animals that express pathological forms of aggression are characterized by a low
      resting heart rate.

PMID- 18817795
TI  - Reproductive experience alters corticosterone and CBG levels in the rat dam.
AB  - Reproductive experience has significant effects on the brain, behavior and
      hormone profiles of the mother. Recent work has demonstrated that primiparous
      rats exhibit decreased dendritic arborizations in the hippocampus, and enhanced
      hippocampus-dependent spatial memory performance at the time of weaning compared
      to nulliparous and, to a lesser degree, multiparous rats. Interestingly, enhanced
      spatial learning and reduced dendritic arbors are seen in nulliparous female rats
      exposed to chronic stress or repeated corticosterone administration. Based on
      these observations, we hypothesized that corticosterone may be altered in
      primiparous rats compared to multiparous and nulliparous rats. The present study
      investigated whether the levels of circulating corticosterone and its binding
      protein, corticosteroid binding globulin (CBG), are altered with reproductive
      experience and pup-exposure during late pregnancy and the postpartum. Total serum
      corticosterone and CBG were assayed from five groups; multiparous, primiparous,
      nulliparous, primip-no-pups, and sensitized rats during gestation (days 14 and
      19) and the postpartum period (days 1, 5, 14, 21, and 35). Results show that
      primiparous rats had significantly elevated total corticosterone on postpartum
      day 1. In addition, primiparous and multiparous rats had significantly lower CBG
      throughout the postpartum period than all other groups, with primiparous rats
      exhibiting lower levels than multiparous rats during mid-lactation. These data
      suggest that free corticosterone is elevated in both primiparous and multiparous
      dams and is elevated to a greater degree in primiparous compared to multiparous
      dams during lactation. Corticosterone and CBG levels were positively correlated
      with specific maternal behaviors during the first week postpartum in parturient
      rats, but not in sensitized rats, suggesting a role for corticosterone in the
      modulation of maternal behavior in parturient rats alone.

PMID- 18817796
TI  - Exposure to pups influences the strength of maternal motivation in virgin female
      rats.
AB  - Following repeated exposure to foster pups, virgin female rats acquire and
      eventually express a full spectrum of maternal caretaking behaviors directed
      toward pups. Though these behaviors are vigorous, these females are reportedly
      less motivated to seek out and interact with pups (i.e. maternally motivated)
      than parturient females during early postpartum. The present study systematically
      assesses how the length of pup-exposure and nature of interactions between the
      female-pup dyad affect maternal motivation in the virgin female rat. Virgin
      females were exposed to young pups consistently (24 h/day) across a prolonged
      period (21 days), briefly (1 h/day) across a relatively brief period (7 days), or
      distally (pups inaccessible in mesh bag). During final pup-exposure days, females
      were conditioned and tested for their preference for a pup-associated chamber
      (e.g. maternal motivation) using conditioned place preference. Early postpartum
      females provided a comparison group. Fully maternal behavior only emerged in
      females given prolonged pup-exposure; this behavior improved significantly over
      time and was maximally expressed for a duration equivalent to early postpartum.
      Females given brief pup-exposure expressed only emergent maternal behaviors
      initiated by pups; distal pup-exposure evoked pup-avoidance. Virgin females given
      prolonged or brief pup-exposure expressed substantial pup-associated chamber
      preference, with more females preferring the pup-associated chamber following
      longer pup-exposures in a subtle stepwise relationship. Maternal motivation was
      strikingly similar in prolonged pup-exposure virgin and early postpartum females.
      Females given distal pup-exposure completely lacked maternal motivation. Maternal
      behavior did not predict chamber preference. Results suggest that pup-exposure,
      regardless of length, is sufficient to support strong maternal motivation,
      whereas parity is not required.

PMID- 18817797
TI  - The influence of simvastatin, atorvastatin and high-cholesterol diet on
      acetylcholinesterase activity, amyloid beta and cholesterol synthesis in rat
      brain.
AB  - OBJECTIVE: There is evidence to suppose that cholesterol-lowering medicine might
      confer protection against dementia, probably via modulation of cholesterol
      synthesis in the brain. The aim of the present study was to investigate the
      potential influence of statins and cholesterol diet on selected parameters
      relevant to Alzheimer's disease pathophysiology. METHODS: For 15 days, rats were
      orally administered simvastatin (10 or 20mg/kg b.wt.), atorvastatin (10 or
      20mg/kg b.wt.), or aqua (control group); and one group was fed high-cholesterol
      (2%) diet. At the end of experiments brain (and plasma) cholesterol, lathosterol,
      hydroxymethylglutaryl-coenzyme A reductase protein, acetylcholinesterase
      activity, amyloid beta (40 and 42) and cholesterol synthesis rate (using the
      incorporation of deuterium from deuterated water) were determined and
      statistically compared to those of aqua. RESULTS: Both statins were able to lower
      cholesterol in the plasma, but none elicited an effect on total brain
      cholesterol. Significant reductions of brain lathosterol and cholesterol
      synthesis rate were observed after simvastatin and atorvastatin treatment.
      Acetylcholinesterase activity, amyloid beta and hydroxymethylglutaryl-coenzyme A
      reductase levels remained unaffected by the two drugs. CONCLUSIONS: This study
      brings additional evidence of a role for statins in cholesterol synthesis in the
      brain. Our data question the relationship between amyloid beta,
      acetylcholinesterase activity and cholesterol synthesis in the rat brain as well
      as the assumption about no exchange between peripheral and brain cholesterol
      pools.

PMID- 18817798
TI  - Steroidal saponins and cytoxicity of the wild edible vegetable-Smilacina
      atropurpurea.
AB  - Four new steroidal saponins, smilacinoside A (1), B (2), C (3), and D (4),
      together with three known saponins, funkioside D (5), aspidistrin (6) and 26-O
      beta-d-glucopyranosyl-22-methoxyl-(25R)-furost-5-en-3beta,26-diol 3-O-beta-d
      glucopyranosyl-(1-->2)-beta-d-glucopyranosyl-(1-->4)-beta-d-galactopyranoside (7)
      were isolated from the dried tender aerial parts of Smilacina atropurpurea
      (Franch.) Wang et Tang. The structures of new compounds were elucidated as
      diosgenin 3-O-alpha-l-rhamnopyranosyl-(1-->2)-O-beta-d-galactopyranoside (1),
      diosgenin 3-O-alpha-l-rhamnopyranosyl-(1-->3)-[6-O-palmitoxyl]-O-beta-d
      galactopyranoside (2), 26-O-beta-d-glucopyranosyl-(25R)-furost-5-en-3beta,22xi,26
      triol 3-O-alpha-l-rhamnopyranosyl-(1-->2)}-beta-d-galactopyranoside (3) and 26-O
      beta-d-glucopyranosyl-22-methoxyl-(25R)-furost-5-en-3beta,26-diol 3-O-alpha-l
      rhamnopyranosyl-(1-->2)-beta-d-galactopyranoside (4) on the basis of chemical
      methods and detailed spectroscopic analysis, including 1D and 2D NMR techniques
      and single-crystal X-ray diffraction, respectively. Six of these compounds and
      MeOH extract were tested for their in vitro cytotoxicity toward K562 human tumor
      cells by an improved MTT method. Smilacinoside A, funkioside D and aspidistrin
      exhibited significant in vitro cytotoxicity against K562 with IC(50) values of
      1.09, 2.93 and 0.47microg/mL, respectively.

PMID- 18817799
TI  - Population differentiation and migration: coalescence times in a two-sex island
      model for autosomal and X-linked loci.
AB  - Evolutionists have debated whether population-genetic parameters, such as
      effective population size and migration rate, differ between males and females.
      In humans, most analyses of this problem have focused on the Y chromosome and the
      mitochondrial genome, while the X chromosome has largely been omitted from the
      discussion. Past studies have compared F(ST) values for the Y chromosome and
      mitochondrion under a model with migration rates that differ between the sexes
      but with equal male and female population sizes. In this study we investigate
      rates of coalescence for X-linked and autosomal lineages in an island model with
      different population sizes and migration rates for males and females, obtaining
      the mean time to coalescence for pairs of lineages from the same deme and for
      pairs of lineages from different demes. We apply our results to microsatellite
      data from the Human Genome Diversity Panel, and we examine the male and female
      migration rates implied by observed F(ST) values.

PMID- 18817800
TI  - Biguanide-induced mitochondrial dysfunction yields increased lactate production
      and cytotoxicity of aerobically-poised HepG2 cells and human hepatocytes in
      vitro.
AB  - As a class, the biguanides induce lactic acidosis, a hallmark of mitochondrial
      impairment. To assess potential mitochondrial impairment, we evaluated the
      effects of metformin, buformin and phenformin on: 1) viability of HepG2 cells
      grown in galactose, 2) respiration by isolated mitochondria, 3) metabolic poise
      of HepG2 and primary human hepatocytes, 4) activities of immunocaptured
      respiratory complexes, and 5) mitochondrial membrane potential and redox status
      in primary human hepatocytes. Phenformin was the most cytotoxic of the three with
      buformin showing moderate toxicity, and metformin toxicity only at mM
      concentrations. Importantly, HepG2 cells grown in galactose are markedly more
      susceptible to biguanide toxicity compared to cells grown in glucose, indicating
      mitochondrial toxicity as a primary mode of action. The same rank order of
      potency was observed for isolated mitochondrial respiration where preincubation
      (40 min) exacerbated respiratory impairment, and was required to reveal
      inhibition by metformin, suggesting intramitochondrial bio-accumulation.
      Metabolic profiling of intact cells corroborated respiratory inhibition, but also
      revealed compensatory increases in lactate production from accelerated
      glycolysis. High (mM) concentrations of the drugs were needed to inhibit
      immunocaptured respiratory complexes, supporting the contention that
      bioaccumulation is involved. The same rank order was found when monitoring
      mitochondrial membrane potential, ROS production, and glutathione levels in
      primary human hepatocytes. In toto, these data indicate that biguanide-induced
      lactic acidosis can be attributed to acceleration of glycolysis in response to
      mitochondrial impairment. Indeed, the desired clinical outcome, viz., decreased
      blood glucose, could be due to increased glucose uptake and glycolytic flux in
      response to drug-induced mitochondrial dysfunction.

PMID- 18817801
TI  - Biotransformation of 2,3,3,3-tetrafluoropropene (HFO-1234yf).
AB  - 2,3,3,3-Tetrafluoropropene (HFO-1234yf) is a non-ozone-depleting fluorocarbon
      replacement with a low global warming potential which has been developed as
      refrigerant. The biotransformation of HFO-1234yf was investigated after
      inhalation exposure. Male Sprague-Dawley rats were exposed to air containing
      2000, 10,000, or 50,000 ppm HFO-1234yf for 6 h and male B6C3F1 mice were exposed
      to 50,000 ppm HFO-1234yf for 3.5 h in a dynamic exposure chamber
      (n=5/concentration). After the end of the exposure, animals were individually
      housed in metabolic cages and urines were collected at 6 or 12-hour intervals for
      48 h. For metabolite identification, urine samples were analyzed by (1)H-coupled
      and decoupled (19)F-NMR and by LC/MS-MS or GC/MS. Metabolites were identified by
      (19)F-NMR chemical shifts, signal multiplicity, (1)H-(19)F coupling constants and
      by comparison with synthetic reference compounds. In all urine samples, the
      predominant metabolites were two diastereomers of N-acetyl-S-(3,3,3-trifluoro-2
      hydroxy-propyl)-l-cysteine. In (19)F-NMR, the signal intensity of these
      metabolites represented more than 85% (50,000 ppm) of total (19)F related signals
      in the urine samples. Trifluoroacetic acid, 3,3,3-trifluorolactic acid, 3,3,3
      trifluoro-1-hydroxyacetone, 3,3,3-trifluoroacetone and 3,3,3-trifluoro-1,2
      dihydroxypropane were present as minor metabolites. Quantification of N-acetyl-S
      (3,3,3-trifluoro-2-hydroxy-propyl)-l-cysteine by LC/MS-MS showed that most of
      this metabolite (90%) was excreted within 18 h after the end of exposure (t(1/2)
      app. 6 h). In rats, the recovery of N-acetyl-S-(3,3,3-trifluoro-2-hydroxy-propyl)
      l-cysteine excreted within 48 h in urine was determined as 0.30+/-0.03, 0.63+/
      0.16, and 2.43+/-0.86 micromol at 2000, 10,000 and 50,000 ppm, respectively
      suggesting only a low extent (<<1% of dose received) of biotransformation of HFO
      1234yf. In mice, the recovery of this metabolite was 1.774+/-0.4 mumol.
      Metabolites identified after in vitro incubations of HFO-1234yf in liver
      microsomes from rat, rabbit, and human support the metabolic pathways of HFO
      1234yf revealed in vivo. The obtained results suggest that HFO-1234yf is
      subjected to a typical biotransformation reaction for haloolefins, likely by a
      cytochrome P450 2E1-catalyzed formation of 2,3,3,3-tetrafluoroepoxypropane at low
      rates, followed by glutathione conjugation or hydrolytic ring opening.

PMID- 18817802
TI  - A novel serine protease from the snake venom of Agkistrodon blomhoffii
      ussurensis.
AB  - A novel serine protease, ABUSV-SPase, was isolated to homogeneity for the first
      time from Chinese Agkistrodon blomhoffii ussurensis snake venom, and its
      enzymatic and structural properties were characterized by multiple techniques.
      ABUSV-SPase is a stable monomeric protein with a molecular mass of 26,752.6a.m.u.
      It reacts optimally with its substrate Nalpha-tosyl-l-arginine methyl ester
      (TAME) at pH 7.0 and 41 degrees C. ESI-MS/MS analysis indicates that ABUSV-SPase
      is a new serine protease, sharing peptide homologies with various snake venom
      serine proteases, especially the snake venom thrombin-like enzymes of this group,
      and serine protease precursors. It is a zinc-containing protein, and although
      zinc is not essential for activity, its replacement by various divalent metal
      ions, including Mg2+, Mn2+, and Ca2+, increases the TAME hydrolysis activity of
      the enzyme. The intrinsic fluorescences of Tyr and Trp residues of ABUSV-SPase
      have emission wavelengths red-shifted by 12.8nm and 3.6nm from those of free Tyr
      and Trp, respectively. The zinc ion increases the hydrophobicity of the
      environment of the Trp residues, increases the thermostability of the protein,
      and affects the protein secondary structure to stabilize the enzyme, but appears
      to have no direct role in its esterase hydrolysis activity.

PMID- 18817803
TI  - Robust perceptual learning of faces in the absence of sleep.
AB  - This study examines the effects of sleep on learning in a face identification
      task. Five groups of subjects performed a 1-of-10 face identification task in two
      sessions separated by 3, 12, and 24h. Session 1 consisted of four blocks of 105
      trials each; Session 2 consisted of eight blocks of trials. All groups exhibited
      significant improvement in response accuracy within each session. Furthermore,
      between-session learning - defined as the difference in proportion correct
      between sessions 1 and 2 - was significant for all groups. Between-session
      learning was greater in groups that slept between sessions, but the effect was
      small and affected performance only in the first block of trials in Session 2.
      Overall, we find that sleep's contribution is a small proportion of the total
      amount learned in face identification, with improvements continuing to accrue in
      its absence.

PMID- 18817805
TI  - The effects of midazolam on the acquisition and expression of fructose- and
      maltodextrin-based flavour preferences.
AB  - The effects of the benzodiazepine agonist midazolam on the acquisition and
      expression of flavour preferences were investigated. Rats (Experiment 1) were
      given one-bottle training with one flavoured solution (CS+) mixed with either
      fructose or maltodextrin and another solution (CS-) presented alone. Animals
      receiving 1 mg/kg midazolam during training consumed more CS- than did animals
      receiving vehicle injections although there was no drug effect on CS+
      consumption. In two-bottle tests the CS+ was preferred to the CS- with the
      preference being larger in fructose trained animals. Midazolam (0.3-3 mg/kg)
      increased total intake but not CS+ preference. Training under midazolam reduced
      the CS+ preference when fructose, but not maltodextrin, was the reinforcer. In
      Experiment 2 training consumption was restricted to 10 ml/session. This removed
      the difference in CS+ preference between reinforcer types but otherwise the
      results were as in Experiment 1. The midazolam induced attenuation of fructose
      based preferences might reflect an increase in CS- palatability during training
      which would reduce the difference between the reinforced and non-reinforced
      solutions. As maltodextrin supports preferences due to post-ingestive effects
      manipulation of palatability should be ineffective. Midazolam does not influence
      the expression of conditioned flavour preferences despite prior evidence that
      benzodiazepine agonists enhance palatability.

PMID- 18817804
TI  - The role of judgment frames and task precision in object attention: Reduced
      template sharpness limits dual-object performance.
AB  - Multiple attributes of a single-object are often processed more easily than
      attributes of different objects-a phenomenon associated with object attention.
      Here we investigate the influence of two factors, judgment frames and judgment
      precision, on dual-object report deficits as an index of object attention. [Han,
      S., Dosher, B., & Lu, Z.-L. (2003). Object attention revisited: Identifying
      mechanisms and boundary conditions. Psychological Science, 14, 598-604] predicted
      that consistency of the frame for judgments about two separate objects could
      reduce or eliminate the expression of object attention limitations. The current
      studies examine the effects of judgment frames and of task precision in
      orientation identification and find that dual-object report deficits within one
      feature are indeed affected modestly by the congruency of the judgments and more
      substantially by the required precision of judgments. The observed dual-object
      deficits affected contrast thresholds for incongruent frame conditions and for
      high precision judgments and reduce psychometric asymptotes. These dual-object
      deficits reflect a combined effect of multiplicative noise and external noise
      exclusion in dual-object conditions, both related to the effects of attention on
      the tuning of perceptual templates. These results have implications for
      modification of object attention theory, for understanding limitations on
      concurrent tasks.

PMID- 18817806
TI  - Intracerebroventricular fluvoxamine administration inhibited pain behavior but
      increased Fos expression in affective pain pathways.
AB  - Anti-nociceptive effects of fluvoxamine, administered by intracerebroventricular
      (i.c.v.) injection, include inhibited pain behavior in both formalin-induced
      acute pain (p<0.05-0.01) and sciatic nerve ligation-allodynia (p<0.03). A 5-HT1
      receptor antagonist (WAY-100635) and a 5-HT2 receptor antagonist (ketanserin),
      injected i.c.v., induced hyperalgesia and inhibited fluvoxamine's anti
      nociceptive effects. We also investigated how fluvoxamine affects neural
      activities in brain areas involved in affectional pain using Fos-like protein
      immunohistochemistry. The acute pain and allodynia increased Fos-positive cells
      in the prefrontal cortex (PFC), basolateral nucleus (BL) and central nucleus of
      the amygdala (Ce), indicating that these areas are involved in pain processing.
      Fluvoxamine did not block the Fos expression, though it did produce anti
      nociception. Moreover, fluvoxamine alone increased Fos in the BL and PFC.
      Ketanserin did not decrease the Fos expression induced by fluvoxamine. The
      results indicated that 5-HT2 receptor activities participate minimally in Fos
      induction by fluvoxamine in the PFC and BL. In contrast, WAY-100635 affected the
      Fos expression produced by fluvoxamine. In the portion of the brain with
      affectional pain pathways, 5-HT1 receptor activities induced anti-nociceptive
      effects and decreased Fos expression with fluvoxamine, while 5-HT2 receptor
      activation affected to anti-nociceptive effects but did not induce Fos
      expression.

PMID- 18817807
TI  - Individual differences in initial low-dose cocaine-induced locomotor activity and
      locomotor sensitization in adult outbred female Sprague-Dawley rats.
AB  - Sex and individual differences are important considerations when studying cocaine
      responsiveness. We have previously shown that male Sprague-Dawley (S-D) rats can
      be classified as low or high cocaine responders (LCRs or HCRs, respectively)
      based on their locomotor activity following a single dose of cocaine (10 mg/kg,
      i.p.). Further, this distinction was found to predict dopamine transporter
      function, cocaine-induced locomotor sensitization, cocaine conditioned place
      preference and motivation to self-administer cocaine. Here we investigated
      whether or not individual differences in cocaine-induced locomotor activity and
      locomotor sensitization exist in female S-D rats. Female rats exhibited a broad
      range of locomotor activation following either a 5 or 10 mg/kg cocaine injection,
      allowing for classification as LCRs or HCRs. When administered over 7 days, both
      doses induced locomotor sensitization in female LCRs/HCRs. However, the magnitude
      of effects produced by 5 mg/kg cocaine in female LCRs/HCRs was more comparable to
      that produced by 10 mg/kg in male LCRs/HCRs, both of which, interestingly,
      developed sensitization in this study. These findings suggest that female S-D
      rats, like male S-D rats, can be classified as LCRs/HCRs and highlight the
      importance of accounting for dose when studying sex and individual differences to
      the effects of cocaine.

PMID- 18817808
TI  - Effects of the nicotinic receptor partial agonists varenicline and cytisine on
      the discriminative stimulus effects of nicotine in rats.
AB  - The nicotinic partial agonist varenicline (VCL) is a recently approved medication
      for the treatment of tobacco dependence, yet very little preclinical research on
      this drug has been published. The present experiment examined the nicotinic
      partial agonist properties of VCL and its parent compound, cytisine (CYT), in a
      nicotine discrimination assay. Rats were trained to discriminate nicotine (0.4
      mg/kg, s.c.) from saline using a two-lever discrimination procedure, followed by
      generalization and antagonism tests with VCL and CYT. Antagonism was examined
      across a range of nicotine doses. In generalization tests, VCL produced a maximum
      of 63% responding on the nicotine-appropriate lever, indicating partial
      generalization. In antagonism tests, VCL decreased the % responding on the
      nicotine-appropriate lever at 0.2 and 0.4 mg/kg nicotine, indicating antagonism
      of nicotine's discriminative stimulus effects. No dose of VCL produced
      significant effects on response rate. The two highest doses of CYT weakly
      substituted for nicotine, producing a maximum of 23% nicotine-appropriate
      responding. CYT produced a weak antagonism of the discrimination of moderate
      nicotine doses, but not of the training dose. These results demonstrate that VCL
      and CYT partially generalize to and partially antagonize nicotine's
      discriminative stimulus effects, consistent with a partial agonist mechanism of
      action.

PMID- 18817809
TI  - Sustainability of health and lifestyle improvements following a non-dieting
      randomised trial in overweight women.
AB  - OBJECTIVE: To compare three non-dieting interventions that focused on lifestyle
      change rather than weight loss, in terms of the sustainability of improvements in
      lifestyle behaviors, psychological well-being and medical symptoms at 2 years.
      METHOD: In Dunedin, New Zealand in 2002/2003, 225 obese/overweight women (BMI >
      or = 28; 25-68 years) participated in a randomised, intention-to-treat trial
      comparing two group programs (P1, P2) and a self-guided mail-delivered program
      (P3). Only P1 included intensive relaxation response training. All three non
      dieting interventions involved a 10-week program, followed by an eight-month
      support phase. Participants completed baseline, 1-year and 2-year assessments.
      Outcomes included behavioral, psychological and medical symptom measures and a
      composite success score. RESULTS: 118 participants completed the 2-year follow
      up. Only among P1 participants were the reductions in psychological distress and
      medical symptoms achieved at 1 year, also maintained at 2 years. At 2 years, P1
      participants had significantly greater increases in stress management behaviors
      than those in P2 (p<0.05), and significantly greater success scores than those in
      P3 (p<0.05). In all three programs, mean weight was unchanged at 2 years.
      CONCLUSION: Inclusion of relaxation response training in a healthy lifestyle
      program facilitates long-term maintenance of psychological and medical symptom
      improvements even in the absence of weight loss.

PMID- 18817810
TI  - How likely are older people to take up different falls prevention activities?
AB  - OBJECTIVE: To determine the extent to which older people are willing to engage in
      different falls prevention activities, and how this may vary in different sectors
      of the older population. METHODS: A survey sent to patients aged over 54 in ten
      general practices in the Southampton, Bristol and Manchester areas of the UK in
      2006 yielded 5,440 respondents. The survey assessed willingness to attend classes
      of strength and balance training (SBT), carry out SBT at home, or accept support
      to reduce home hazards. Participants were asked their gender, age, education,
      home tenure, ethnic group, and how often they had fallen during the past year.
      RESULTS: Over 60% of the sample would consider doing SBT at home and 36.4% said
      they would definitely do SBT at home. Only 22.6% would definitely attend group
      sessions and 41.1% would definitely not attend. Older age, recent falls and lower
      socioeconomic status were associated with a greater willingness to carry out SBT
      at home (but not in classes) and accept help with home hazards. CONCLUSIONS:
      Health promotion programmes should give prominence to home-based performance of
      SBT as a method of encouraging the entire older population to engage in falls
      prevention, including those most in need.

PMID- 18817812
TI  - Aluminium-induced electrophysiological, biochemical and cognitive modifications
      in the hippocampus of aging rats.
AB  - Aluminium (Al) is the most abundant metal known for its neurotoxicity in humans.
      It gains easy access to the central nervous system under normal physiological
      conditions and accumulates in different brain regions. It has been reported to be
      involved in the etiology of several neurodegenerative diseases. In this study, we
      have investigated the effects of long-term intake of aluminium chloride (AlCl(3))
      on the electrophysiological, behavioral, biochemical and histochemical functions
      of hippocampus. Wistar rats were fed with AlCl(3) at a dose of 50mg/(kgday) for 6
      months in the drinking water. Effect of long-term intake of Al was studied on the
      electrical activity of hippocampal CA1 and CA3 regions in brain of young and old
      rats. Morris water maze and open field tests were performed to investigate the
      cognitive and anxiety status of aging rats intoxicated with aluminium. Our
      studies indicate that aluminium intake results in increased multiple unit
      activity and adversely affect the spatial learning and memory abilities of both
      young and old rats. Aluminium intake also inflicts oxidative stress-related
      damage to lipids, membrane associated proteins (Na-K ATPase and PKC) and
      endogenous antioxidant enzyme activity (SOD, GPx and GST). The compromised
      antioxidant system might be playing a crucial role in the observed Al-induced
      alterations. We have observed that the magnitude of AlCl(3)-induced alteration
      was considerably higher in younger group of rats compared to older group. In
      conclusion, the results of the present study implicates that aluminium treatment
      exerts its neurotoxic effects by altering the overall physiology of brain, and
      the induced changes were strongly correlated with each other.

PMID- 18817813
TI  - Identification and validation of control cell lines for accurate parkin dosage
      analysis.
AB  - Mutation of the parkin gene (parkin) is the most common cause of early-onset
      Parkinson's disease and to date over 100 different mutations have been described.
      However, screening of parkin is complicated by its genomic architecture and
      context. Notably, dosage alterations in parkin account for greater than 50% of
      mutations detected in some cohort studies. To improve the accuracy and
      reproducibility of parkin genomic dosage assays we have identified and analysed
      cell lines with chromosomal abnormalities affecting 6q26. FISH and real-time PCR
      analysis identified cell lines with reduced or increased copy number spanning the
      entire parkin locus. These cell lines represent a valuable resource to facilitate
      accurate copy number determination of any parkin exon. The reagents are easily
      obtainable and are compatible with current quantitative technologies and
      platforms.

PMID- 18817811
TI  - Early life stress as a risk factor for mental health: role of neurotrophins from
      rodents to non-human primates.
AB  - Early adverse events can enhance stress responsiveness and lead to greater
      susceptibility for psychopathology at adulthood. The epigenetic factors involved
      in transducing specific features of the rearing environment into stable changes
      in brain and behavioural plasticity have only begun to be elucidated.
      Neurotrophic factors, such as nerve growth factor (NGF) and brain-derived
      neurotrophic factor (BDNF), are affected by stress and play a major role in brain
      development and in the trophism of specific neuronal networks involved in
      cognitive function and in mood disorders. In addition to the central nervous
      system, these effectors are produced by peripheral tissues, thus being in a
      position to integrate the response to external challenges. In this paper we will
      review data, obtained from animal models, indicating that early maternal
      deprivation stress can affect neurotrophin levels. Maladaptive or repeated
      activation of NGF and BDNF, early during postnatal life, may influence stress
      sensitivity at adulthood and increase vulnerability for stress-related
      psychopathology.

PMID- 18817814
TI  - Treatment with phosphotidylglycerol-based nanoparticles prevents motor deficits
      induced by proteasome inhibition: implications for Parkinson's disease.
AB  - Failure of the ubiquitin-proteasome system to degrade abnormal proteins may
      underlie the accumulation of alpha-synuclein and dopaminergic neuronal
      degeneration that occurs in Parkinson's disease. Consequently, a reduction of
      functional proteasome activity has been implicated in Parkinson's disease. VP025
      (Vasogen Inc.) is a preparation of phospholipid nanoparticles incorporating
      phosphatidylglycerol that has been shown to have neuroprotective effects. We show
      that VP025 prevents the deficits in motor coordination and dopamine observed in a
      proteasome inhibitor rat model of PD. Thus, VP025 may have a therapeutic effect
      on the impairment of dopaminergic-mediated motor activity induced by proteasome
      inhibition.

PMID- 18817815
TI  - Age differences in the formation and use of cognitive maps.
AB  - Topographical orientation relies on the integrity of several cognitive functions
      and different strategies that individuals may adopt while navigating in the
      environment. Although previous studies have shown an age-related decline in
      navigational ability, these have not clarified the precise function or strategy
      that is affected. We hypothesized that aging may have an adverse effect on the
      ability to form and use a 'cognitive map', a mental representation of the
      environment. We had young and older participants solve a navigational task in a
      virtual environment designed to assess cognitive map use. Older participants
      required more time to form a cognitive map of the environment than young
      individuals and required more time and made more errors when subsequently using
      the cognitive map for orientation. These results suggest that decreased efficacy
      in both forming and using cognitive maps makes a significant contribution to the
      age-related decline in orientation skills.

PMID- 18817816
TI  - Antidepressant-like effects of sodium butyrate in combination with estrogen in
      rat forced swimming test: involvement of 5-HT(1A) receptors.
AB  - Sodium butyrate (NaB), a histone deacetylase inhibitor, has been implicated in
      the antidepressant-like effects either injected as a single drug or in
      combination with selective serotonin reuptake inhibitor (SSRI), such as
      fluoxetine. Estrogen is also demonstrated to have antidepressant effect
      especially together with fluoxetine. We investigated whether NaB administered in
      combination with estradiol benzoate (EB) exerted antidepressant-like effect in
      forced swimming test (FST) in ovariectomized female rats. Furthermore, we
      detected the mRNA expressions of serotonin receptors and neuropeptides in
      hypothalamus, both of which participate in the mood disorder. Ovariectomized
      female SD rats were treated with vehicle, NaB, EB or NaB combined with EB for 7
      days and then subjected to FST. The expressions of serotonin receptors (5
      hydroxytryptamine receptor), corticotropin-releasing hormone (CRH) and arginine
      vasopressin (AVP) mRNA in the hypothalamus were detected by real time PCR. We
      found that co-treated with NaB and EB resulted in a significant decrease in
      immobility behavior in FST, a measure for depression-like behavioral. 5-HT(1A)
      antagonist, WAY 100635, significantly block the antidepressant-like effects
      induced by NaB plus EB. The mRNA expression of the serotonin-1A [5
      hydroxytryptamine 1A (5-HT(1A))] receptor was increased in the co-treated group
      in hypothalamus, while there was no difference in the mRNA expression of 5-HT(2A)
      or 5-HT(2C). The mRNA expression of CRH or AVP was not significantly altered
      either. In conclusion, NaB may exert antidepressant-like effects in combination
      with EB in ovariectomized female rats through 5-HT(1A) receptor, via altering the
      expression of 5-HT(1A) in the hypothalamus.

PMID- 18817817
TI  - Repression of CFTR activity in human MMNK-1 cholangiocytes induces
      sulfotransferase 1E1 expression in co-cultured HepG2 hepatocytes.
AB  - Mouse models of cystic fibrosis (CF) indicate that sulfotransferase (SULT) 1E1 is
      significantly induced in livers of many mice lacking cystic fibrosis
      transmembrane receptor (CFTR) activity. Increased SULT1E1 activity results in the
      alteration of estrogen-regulated protein expression in the livers of these mice.
      In this study, human MMNK-1 cholangiocytes with repressed CFTR function were used
      to induce SULT1E1 expression in human HepG2 hepatocytes to investigate whether
      SULT1E1 can be increased in human CF liver. CFTR expression was inhibited in MMNK
      1 cholangiocytes using CFTR-siRNA, then the MMNK-1 and HepG2 cells were co
      cultured in a membrane-separated Transwell system. Expression of SULT1E1 and
      selected estrogen-regulated proteins were then assayed in the HepG2 cells.
      Results demonstrate that inhibition of CFTR expression in MMNK-1 cells results in
      the induction of SULT1E1 message and activity in HepG2 cells in the Transwell
      system. The expression of estrogen-regulated proteins including insulin-like
      growth factor (IGF)-1, glutathione-S-transferase (GST) P1 and carbonic anhydrase
      (CA) II expression are repressed in the HepG2 cells cultured with the CFTR-siRNA
      MMNK-1 cells apparently in response to the increased sulfation of beta-estradiol.
      Thus, we have shown that co-culture of HepG2 hepatocytes with MMNK-1
      cholangiocytes with siRNA repressed CFTR expression results in the selective
      induction of SULT1E1 in the HepG2 cells. Loss of CFTR function in cholangiocytes
      may have a paracrine regulatory effect on hepatocytes via the induction of
      SULT1E1 and the increased sulfation of beta-estradiol. Experiments are presently
      underway in our laboratory to elucidate the identity of these paracrine
      regulatory factors.

PMID- 18817818
TI  - A comparative study of the ability of EMA and PMA to distinguish viable from heat
      killed mixed bacterial flora from fish fillets.
AB  - Ethidium bromide monoazide (EMA) and propidium monoazide (PMA) were utilized to
      selectively allow real-time PCR (Rti-PCR) amplification of target DNA from viable
      but not heat killed cells from the mixed bacterial flora derived from cod
      fillets. A linear range of DNA amplification was exhibited from 3.2x10(2) to
      1.0x10(5) genomic targets per Rti-PCR. Following the heat treatment of cell
      suspensions the surviving populations with the EMA and PMA Rti-PCR method were
      evaluated by comparison with plate counts and MPN assays following different heat
      exposures (45 to 95 degrees C) for 5 min. The percent of erroneous survival with
      PMA Rti-PCR was higher than with EMA treatment. Cellular leakage was examined by
      following the extracellular increase of 260 and 280 nm absorbing materials.
      Initial leakage of protein and nucleic acids occurred at 50 degrees C, the
      maximal amount of leakage occurred at 70 degrees C.

PMID- 18817819
TI  - Altered regioselectivity of a poplar O-methyltransferase, POMT-7.
AB  - O-Methylated flavonoids are biosynthesized by regioselective flavonoid O
      methyltransferases (OMTs), which may account for the limited number of naturally
      occurring flavonoids in nature. It was previously shown that poplar POMT-7
      regioselectively methylates the 7-hydroxyl group of flavones, whereas rice ROMT-9
      regioselectively methylates the 3'-hydroxyl group of the substrate. We co
      expressed both OMT genes (POMT-7 and ROMT-9) in E. coli and carried out
      biotransformation experiments of some flavonoids with the transformed E. coli
      strain. Contrast to the predicted regioselectivity of both POMT-7 and ROMT-9,
      unexpected methylation reaction products, i.e. 3',4'-O-methylated flavonoids, in
      addition to the predicted ones, were obtained with luteolin (5,7,3',4'
      tetrahydroxyflavone) and quercetin (3,5,7,3',4'-pentahydroxyflavone) as
      substrates. Reactions using the 3'-O-methyl derivative of luteolin and quercetin
      by POMT-7 revealed that the enzyme has altered its regioselectivity from the 7-
      to the 4'-hydroxyl groups. These results are discussed in terms of molecular
      modeling of POMT-7 in relation to its methyl donor.

PMID- 18817820
TI  - The origins and evolution of "controlled" drug delivery systems.
AB  - This paper describes the earliest days when the "controlled drug delivery" (CDD)
      field began, the pioneers who launched this exciting and important field, and the
      key people who came after them. It traces the evolution of the field from its
      origins in the 1960s to (a) the 1970s and 1980s, when numerous macroscopic
      "controlled" drug delivery (DD) devices and implants were designed for delivery
      as mucosal inserts (e.g., in the eye or vagina), as implants (e.g., sub-cutaneous
      or intra-muscular), as ingestible capsules (e.g., in the G-I tract), as topical
      patches (e.g., on the skin), and were approved for clinical use, to (b) the 1980s
      and 1990s when microscopic degradable polymer depot DD systems (DDS) were
      commercialized, and to (c) the currently very active and exciting nanoscopic era
      of targeted nano-carriers, in a sense bringing to life Ehrlich's imagined concept
      of the "Magic Bullet". The nanoscopic era began with systems proposed in the
      1970s, that were first used in the clinic in the 1980s, and which came of age in
      the 1990s, and which are presently evolving into many exciting and clinically
      successful products in the 2000s. Most of these have succeeded because of the
      emergence of three key technologies: (1) PEGylation, (2) active targeting to
      specific cells by ligands conjugated to the DDS, or passive targeting to solid
      tumors via the EPR effect. The author has been personally involved in the origins
      and evolution of this field for the past 38 years (see below), and this review
      includes information that was provided to him by many researchers in this field
      about the history of various developments. Thus, this paper is based on his own
      personal involvements in the CDD field, along with many historical anecdotes
      provided by the key pioneers and researchers in the field. Because of the huge
      literature of scientific papers on CDD systems, this article attempts to limit
      examples to those that have been approved for clinical use, or are currently in
      clinical trials. Even so, it is impossible to know of and include all such
      examples and to properly credit all the key people who helped to bring the
      various technologies and devices to the clinic. The author apologizes in advance
      for all omissions.

PMID- 18817821
TI  - Multi-ion-crosslinked nanoparticles with pH-responsive characteristics for oral
      delivery of protein drugs.
AB  - pH-Responsive nanoparticles composed of chitosan (CS) and poly-gamma-glutamic
      acid (gamma-PGA) blended with tripolyphosphate (TPP) and MgSO(4) (multi-ion
      crosslinked NPs) were prepared and characterized to determine their effectiveness
      in the oral delivery of insulin. Their counterparts without TPP and MgSO(4) (NPs)
      were used as a control. FT-IR and XRD results indicated that the spontaneous
      interaction between CS, insulin, gamma-PGA, MgSO(4) and TPP can form an ionically
      crosslinked network-structure, leading to the formation of nanoparticles. Multi
      ion-crosslinked NPs were more compact than NPs, while their zeta potential values
      were comparable. During storage, multi-ion-crosslinked NPs suspended in deionized
      water were stable for at least 10 weeks. Multi-ion-crosslinked NPs had a superior
      stability over a broader pH range than NPs. In the in vitro release study, NPs
      failed to provide an adequate retention of loaded insulin in dissolution media
      compared to multi-ion-crosslinked NPs. Transepithelial-electrical-resistance and
      transport experiments demonstrated that multi-ion-crosslinked NPs significantly
      more effectively transported insulin than NPs; confocal visualization further
      validated the enhanced permeation of insulin via the paracellular pathway. The
      aforementioned results suggest that multi-ion-crosslinked NPs are a promising
      carrier for improved transmucosal delivery of insulin in the small intestine.

PMID- 18817822
TI  - The KiSS1/GPR54 system in fish.
AB  - The KiSS1/GPR54 system has now been identified in non-mammalian vertebrates.
      Transcripts encoding for KiSS1 and its receptor, GPR54, have been isolated from a
      number of fish species. The expression of their genes was characterized in the
      context of temporal and spatial expression and in response to endocrine
      manipulations. GPR54 sequence is conserved between mammals and fish, with a
      second receptor sequence identified in zebrafish. The KiSS1 gene sequence is
      highly divergent between mammals and fish, yet the human kisspeptin is capable of
      activating the fish GPR54. As in mammals, the fish KiSS1/GPR54 system appears to
      be partially regulated by gonadal steroids. The data available for fish are
      fragmented, yet indicate that the KiSS1/GPR54 system is functionally conserved in
      non-mammalian vertebrates and supports the notion that it has a role in pubertal
      development and reproduction in piscine systems.

PMID- 18817823
TI  - Role of bone marrow stromal cells in the generation of human CD8+ regulatory T
      cells.
AB  - Fibroblast-like stromal cells exert a strong inhibitory effect on lymphocyte
      proliferation, both directly by interacting with responding lymphocytes and
      indirectly by inducing the generation of regulatory T cells. Indeed, upon
      triggering via the CD3/TCR complex, highly effective CD8(+)regulatory cells
      (CD8(+)Reg(c)) are generated from cocultures of peripheral blood CD8(+)T cells
      and bone-marrow-derived stromal cells. When cell-to-cell interactions occur,
      CD8(+)Reg(c) strongly inhibit lymphocyte proliferation at a ratio of 1:1 to 1:100
      between CD8(+)Reg(c) and responding lymphocytes. Phenotypic analysis indicated
      that CD8(+)Reg(c) are CD25(+)CD28(+) and express low levels of mRNA for Foxp3 but
      they do not bear CTLA4 and glucocorticoid-induced tumor necrosis factor receptor
      antigens. Soluble mediators such as interleukin-10, transforming growth factor
      beta, and prostaglandin E(2) are not involved in the generation of CD8(+)Reg(c)
      from CD8(+) precursors or in the immunosuppressive mechanism mediated by
      CD8(+)Reg(c) on lymphocyte proliferation. Cyclosporin A (CSA) slightly
      downregulated generation of CD8(+)Reg(c) indicating that only a small fraction of
      precursors of CD8(+)Reg(c) are sensitive to this immune-suppressive drug. Along
      this line, treatment of effector CD8(+)Reg(c)with CSA does not affect their
      immunosuppressive effect, indicating that the molecular mechanism of CD8(+)Reg(c)
      mediated regulation is independent of the function of CSA biochemical target
      molecules.

PMID- 18817824
TI  - CD8+ regulatory T cells-A distinct T-cell lineage or a transient T-cell
      phenotype?
AB  - Regulation of the immune system is fundamental for proper immune function and
      homeostasis. In the periphery, regulatory T cells provide self-tolerance and
      protect the host from harmful autoreactive T cells. Regulatory T cells are also
      involved in the pathogenesis of chronic viral infectious diseases and cancer.
      Both the CD4(+) and the CD8(+) T cell compartments contain regulatory T cells.
      Although various CD4(+) regulatory T-cell subsets represent the best
      characterized regulatory T-cell populations, CD8(+) regulatory T cells also have
      strong immunosuppressive properties and are involved in the pathogenesis of
      various clinical conditions. In this review, we will discuss the phenotypic and
      functional characteristics of CD8(+) regulatory T cells in comparison to CD4(+)
      regulatory T cells.

PMID- 18817825
TI  - A translatable molecular approach to determining CD8 T-cell epitopes in TMEV
      infection.
AB  - Defining the epitope specificity of CD8+ T cells is an important goal in
      autoimmune and immune-mediated disease research. We have developed a
      translational molecular approach to determine the epitope specificity of CD8+ T
      cells using the Theiler's murine encephalomyelitis virus (TMEV) model of multiple
      sclerosis (MS). TMEV-specific CD8+ T cells were isolated from brains and spleens
      of 7-day TMEV-infected C57BL/6J mice and stimulated by Cos-7 cells that were co
      transfected with expression vectors encoding the D(b) class I molecule along with
      overlapping segments of the TMEV genome. Both brain-infiltrating and spleen
      derived CD8+ T cells expressed IFN-gamma when Cos-7 cells were co-transfected
      with D(b) class I molecule and the TMEV genomic segment that encoded the
      immunodominant TMEV epitope. This demonstrated that peripheral and brain
      infiltrating CD8+ T-cell responses were focused on peptide epitope(s) encoded by
      the same region of the TMEV genome. We propose that a similar molecular approach
      could also be used to determine the antigen specificity of suppressor CD8 T cells
      by the measurement of transforming growth factor-beta (TGF-beta) production. In
      addition, with a randomly generated library and peripheral blood or isolated CSF
      CD8+ T cells, this would be an effective method of predicting the epitope
      specificity of CD8+ T cells in human inflammatory CNS diseases, in animal models
      of MS or other organ-specific inflammatory diseases with a protective or
      pathogenic role of CD8 T cells.

PMID- 18817826
TI  - Are CD8+CD122+ cells regulatory T cells or memory T cells?
AB  - We identified CD8(+)CD122(+) regulatory T cells in the mouse. Some immunologists
      consider CD8(+)CD122(+) cells to be memory T cells despite our report of their
      regulatory function. Here, we propose a dual phenotype of these cells. Murine
      CD8(+)CD122(+) T cells demonstrate both memory and regulatory features in their
      functional profiles. Human CD8(+)CXCR3(+) T cells, which are thought to be the
      human counterpart of murine CD8(+)CD122(+) regulatory T cells, do not match human
      central memory T cells of the CD8(+)CD45RA(-)CCR7(+) phenotype. Thus, we must
      consider human CD8(+) regulatory T cells and murine CD8(+) regulatory T cells
      separately. Of human CD8(+) regulatory T cells, CD8(+)CXCR3(+) regulatory T cells
      can be divided into further subsets and we may be able to distinguish memory T
      cells and regulatory T cells. Of murine CD8(+)CD122(+) regulatory T cells, it
      seems to be impossible to divide CD8(+)CD122(+)CD44(+)CD62L(+) regulatory T cells
      into further subsets at present, indicating that this single population of cells
      has activities of both regulatory T cells and memory T cells.

PMID- 18817827
TI  - Murine CD8+ regulatory T lymphocytes: the new era.
AB  - Regulatory T lymphocytes unequivocally play a major role in the maintenance of
      immunologic homeostasis. The first descriptions of regulatory T lymphocytes
      concerned CD8(+) cells, but this field was brought into discredit when some of
      its central tenets turned out to be erroneous. CD4(+) regulatory T cells took
      over and, with the help of newly developed molecular tools, rapidly were
      phenotypically and functionally characterized. We now know that these cells
      control a large variety of immune responses. However some observations of in
      vitro or in vivo immune regulation could not be explained with CD4(+) regulatory
      T cell activity and depended on the action of a variety of CD8(+) T cell
      populations. In recent years, substantial progress has been made in the
      phenotypic and functional characterization of CD8(+) regulatory T cells. These
      cells play a role in the control of intestinal immunity, immunopathology, and
      autoimmunity, as well as in immune privilege of the eye, in oral tolerance, and
      in prevention of graft-versus-host disease and graft-rejection. The suppressor
      effector mechanisms used by these cells are in part shared with CD4(+) regulatory
      T cells and in part unique to this population. We here review the current
      literature on naturally occurring and experimentally induced murine CD8(+)
      regulatory T-cell populations.

PMID- 18817828
TI  - CD8+ regulatory T cells, their suppressive mechanisms, and regulation in cancer.
AB  - Regulatory T (Treg) cells induce immune tolerance by suppressing host immune
      responses against self- or nonself-antigens, thus playing critical roles in the
      prevention of autoimmune diseases, but they may inhibit antitumor immunity and
      promote tumor growth. Increasing evidence demonstrates that elevated proportions
      of CD4(+) Treg cells are present in various types of cancers and suppress
      antitumor immunity. However, less is known about CD8(+) Treg cells and their
      detrimental effects on immunotherapy directed toward cancer. Toll-like receptor
      (TLR)-8 signaling may directly regulate the suppressive function of CD4(+) and
      CD8(+) Treg cells. Linking TLR signaling to the functional control of Treg cells
      opens the potential for intriguing opportunities to manipulate TLR signaling to
      control the suppressive function of different subsets of Treg cells for effective
      immunotherapy of cancer.

PMID- 18817829
TI  - Induction of immune tolerance by activation of CD8+ T suppressor/regulatory cells
      in lupus-prone mice.
AB  - Multiple CD8(+) suppressive T cell (Ts) subtypes are now recognized as essential
      regulators of the immune system that prevent autoimmunity through secretion of
      multiple cytokines and the subsequent inhibition of effector lymphocyte function.
      CD8(+) Ts are an exciting area of study because of the possible therapeutic
      implications of inducing suppressive cells that are able to subdue or anergize
      autoimmune manifestations. Current research in systemic lupus erythematosus
      (SLE), a disease in which most effective therapies are widely immunosuppressive,
      is often focused on novel and highly targeted ways in which to treat this
      multiorgan disease. CD8(+) Ts have been impaired in human and murine SLE. Our
      group and others have utilized tolerogenic peptides to induce and study CD8(+) Ts
      to understand their function, as well as investigate a possible new SLE therapy.
      This review will discuss the similarities and differences in CD8(+) Ts subsets,
      the concept of tolerance as a therapy, and the current understanding of CD8(+) Ts
      in mouse SLE models.

PMID- 18817830
TI  - CD8+ suppressor T cells resurrected.
AB  - This review focuses on the role of antigen-specific T cells that mediate active
      inhibition of immune responses over the past 35 years since their initial
      description. The field has experienced several changes in the accepted paradigm
      of such suppressor/regulatory T cells, from initial indications that such cells
      were CD8(+), to the view that such cells did not exist, to the identification of
      the transcription factor Foxp3 as a key orchestrator of inhibitory function.
      Although most Foxp3(+) cells in a resting animal are CD4(+)CD25(+) cells, Foxp3
      expression and inhibitory function can be induced by antigens in the periphery by
      selective cytokine conditions, particularly TGF-beta. Such induced T cells occur
      within both the CD4 and the CD8 T-cell lineages and appear to mediate suppression
      by inhibiting the costimulatory activity of antigen-presenting cells and the
      production of inhibitory cytokines. Recent data generated by analysis of TCR Tg T
      cells that do not select many Foxp3-positive cells during thymic development are
      reviewed, emphasizing the pattern of "linked suppression" and focus of the
      relative potency of different mechanisms of suppression.

PMID- 18817831
TI  - Human leukocyte antigen class I-restricted immunosuppression by human CD8+
      regulatory T cells requires CTLA-4-mediated interaction with dendritic cells.
AB  - We previously reported autoreactive CD8(+) regulatory T cells (Tregs) that were
      expanded and cloned from human peripheral blood by coculture with autologous
      dendritic cells (DC). Here we demonstrate that these CD8(+) Tregs require human
      leukocyte antigen (HLA)-class I restricted activation and then mediate cell
      contact-dependent suppression of CD4(+) T cells. CD8(+) Tregs interacted with DC
      to suppress T-cell responses but DC were not irreversibly altered by this
      interaction because they could subsequently stimulate CD4(+) T cells normally.
      The ability of DC to form conjugates with CD4(+) T cells was reduced in the
      presence of CD8(+) Tregs. Suppression was blocked by Abs to CD80 and CTLA-4,
      implicating CTLA-4:CD80 interactions in the function of CD8(+) Tregs. CD8(+)
      Tregs rapidly express very high levels of surface CTLA-4 following activation
      compared with conventional T cells. Related to this, the expression of TRAT1 mRNA
      (T-cell receptor interacting molecule, or TRIM) was highly upregulated in
      microarray analysis of CD8(+) Tregs compared with conventional cytotoxic or
      nonregulatory CD8(+) T cells. TRIM acts to chaperone CTLA-4 transport to the cell
      surface; this function would be required to account for the phenotypic and
      functional properties of CD8(+) Tregs.

PMID- 18817832
TI  - HLA-G-dependent suppressor cells: Diverse by nature, function, and significance.
AB  - Regulatory cells play a crucial role in the maintenance of the immune homeostasis
      and in pathologic conditions such as those involving transplantations, autoimmune
      diseases, infections, and cancers. The regulatory cells block the function of
      other effector cells and can induce the formation of other regulatory cells.
      Human leukocyte antigen (HLA)-G is a nonclassic class I molecule that functions
      as an immune-tolerogenic molecule with restricted tissue expression. Numerous
      studies have highlighted the role of HLA-G in the context of transplantation,
      cancer, autoimmunity, and hematologic diseases. HLA-G has a direct inhibitory
      effect on immune responses but there is increasing evidence that it also has a
      long term immunomodulatory effect and can induce the generation of
      suppressor/regulatory cells. In this article we review the different natures,
      functions, and significance of the various types of HLA-G-dependent suppressor
      cells.

PMID- 18817833
TI  - Generation and function of human regulatory CD8+ T cells induced by a humanized
      OKT3 monoclonal antibody hOKT3gamma1 (Ala-Ala).
AB  - Recent studies with a humanized anti-CD3 antibody in clinical trials suggested
      that this drug can induce regulatory CD8+ T cells. In this review, we discuss how
      these regulatory human CD8+ cells can be generated and the possible molecular
      tools they may use to inhibit immune responses. We compare our data on CD8+
      regulatory cells induced by anti-CD3 stimulation with those reported in other
      experimental systems to identify both common and unique features of these cells.

PMID- 18817834
TI  - CD8+ T suppressor cells and the ILT3 master switch.
AB  - Similar to helper and cytotoxic T cells, CD8(+) T suppressor cells (Ts) acquire
      antigen specificity via direct interaction with antigen-presenting cells (APC).
      They induce the upregulation of the inhibitory receptor immunoglobulin-like
      transcript (ILT)3 on professional and nonprofessional APC, rendering these cells
      tolerogenic and able to induce the differentiation of further waves of regulatory
      and suppressor T cells. This review sums up evidence that ILT3 is the centerpiece
      of CD8(+) Ts-driven suppression and acts as a master switch in the regulation of
      CD8(+) and CD4(+) T-cell responses to antigens in transplantation, autoimmunity,
      allergy, and cancer.

PMID- 18817835
TI  - Vaccination with 73kDa recombinant heavy chain myosin generates high level of
      protection against Brugia malayi challenge in jird and mastomys models.
AB  - We have earlier reported identification, expression and purification of a 2.0kb
      cDNA clone coding for Brugia malayi heavy chain myosin which exhibited strong
      immuno-reactivity with bancroftian sera from endemic normal (EN) human subjects
      which are considered to be putatively immune. In the present study,
      immunoprophylactic characterization of B. malayi recombinant myosin was carried
      out in rodent models and the protective efficacy was evaluated by assessing the
      microfilarial burden and adult worm counts in vaccinated host after an infective
      larval challenge. Data indicates that immunization resulted in to a significant
      reduction in microfilarial burden (approximately 76%) and adult worm
      establishment (54-58%), accompanied with embryostatic effect (70-75%) in both the
      animal models. The findings suggest that immune-protection by recombinant myosin
      was conferred through both humoral and cellular arms of immunity as indicated by
      an increased antibody titer with predominance of IgG2a and IgG2b isotypes along
      with elevated level of IgG1 apart from significant proliferation of lymphocytes,
      increased nitric oxide production and profound adherence of splenocytes causing
      cytotoxicity to microfilariae and infective larvae. The present study indicates
      that the recombinant B. malayi myosin is a promising vaccine candidate against
      human lymphatic filarial infection.

PMID- 18817836
TI  - The elusive search for an HIV vaccine--and what to do meanwhile.

PMID- 18817837
TI  - Tobacco smoking and MRI/MRS brain abnormalities compared to nonsmokers.
AB  - This mini review emphasizes the fact that tobacco smoking causes small but real
      biologic brain changes that need to be studied in depth. A crucial question is
      whether these anatomical/chemical changes reverse toward normal when smokers
      quit. This review is presented to stimulate further research to answer this
      question.

PMID- 18817838
TI  - Fourier transform infrared study of protein secondary structural changes in the
      muscle of Labeo rohita due to arsenic intoxication.
AB  - Protein is one of the most important nutrients in human diets and fish has become
      an increasingly important source of protein in most of the developing countries.
      Among the various fish tissues, muscle is the major contributor of proteins and
      the whole mass of the body. The goal of this study is to assess the changes in
      the biochemical compositions in general, and the protein structural changes in
      particular, in the muscle of Labeo rohita fingerlings due to arsenic intoxication
      using Fourier transform infrared (FT-IR) spectroscopy. The results of the present
      study indicate that arsenic intoxication induces significant alteration in the
      major biochemical compositions such as proteins, lipids and nucleic acids of
      Labeo rohita. Further, the results clearly indicate considerable change in the
      composition of muscle proteins due to arsenic intoxication. It is therefore
      concluded that FT-IR spectroscopy can be a successful detection tool in
      toxicological research.

PMID- 18817839
TI  - p,p'-DDE induces mitochondria-mediated apoptosis of cultured rat Sertoli cells.
AB  - p,p'-Dichlorodiphenoxydichloroethylene (p,p'-DDE), the major metabolite of
      dichlorodiphenoxytrichloroethane (DDT), is a known persistent organic pollutant
      and male reproductive toxicant. However, the mechanism underlying male
      reproductive toxicity of p,p'-DDE remains limited. In the present study, Sertoli
      cells were used to investigate the molecular mechanism involved in p,p'-DDE's
      male reproductive toxicity. Results showed that p,p'-DDE exposure at over 30
      microM showed induction of apoptotic cell death. p,p'-DDE could induce
      mitochondria-mediated apoptotic changes including elevation in reactive oxygen
      species (ROS) generation, decrease in mitochondrial membrane potential
      (DeltaPsi(m)), and release of cytochrome c into the cytosol, which could be
      blocked by antioxidant agent N-acetyl-l-cysteine (NAC). In addition, elevated
      ratios of Bax/Bcl-w and Bak/Bcl-w and cleavages of procaspase-3 and -9 were
      induced by p,p'-DDE treatment. All of the results suggested that ROS generation
      may play a critical role in the initiation of p,p'-DDE-induced apoptosis by
      mediation of the disruption of DeltaPsi(m), the release of cytochrome c into the
      cytosol and further the activation of caspase cascade.

PMID- 18817840
TI  - A comparative 90-day toxicity study of allyl acetate, allyl alcohol and acrolein.
AB  - Allyl acetate (AAC), allyl alcohol (AAL), and acrolein (ACR) are used in the
      manufacture of detergents, plastics, pharmaceuticals, and chemicals and as
      agricultural agents. A metabolic relationship exists between these chemicals in
      which allyl acetate is metabolized to allyl alcohol and subsequently to the
      highly reactive, alpha,beta-unsaturated aldehyde, acrolein. Due to the weaker
      reactivity of the protoxicants, allyl acetate and allyl alcohol, relative to
      acrolien we hypothesized the protoxicants would attain greater systemic exposure
      and therefore deliver higher doses of acrolein to the internal organs. By
      extension, the higher systemic exposure to acrolein we hypothesized should lead
      to more internal organ toxicity in the allyl acetate and allyl alcohol treated
      animals relative to those treated with acrolein. To address our hypothesis we
      compared the range of toxicities produced by all three chemicals in male and
      female Fischer 344/N rats and B6C3F1 mice exposed 5 days a week for 3 months by
      gavage in 0.5% methylcellulose. Rats (10/group) were dosed with 0-100mg/kg allyl
      acetate, 0-25mg/kg allyl alcohol, or 0-10mg/kg acrolein. Mice (10/group) were
      dosed with 0-125mg/kg allyl acetate, 0-50mg/kg allyl alcohol, or 0-20mg/kg
      acrolein. The highest dose of allyl acetate and acrolein decreased survival in
      both mice and rats. The primary target organ for the toxicity of all three
      chemicals in both species and sexes was the forestomach; squamous epithelial
      hyperplasia was observed following exposure to each chemical. In both species the
      highest allyl acetate dose group exhibited forestomach epithelium necrosis and
      hemorrhage and the highest dose of acrolein led to glandular stomach hemorrhage.
      Liver histopathology was the most apparent with allyl acetate, was also observed
      with allyl alcohol, but was not observed with acrolein. All chemicals had effects
      on the hematopoietic system with allyl acetate having the most pronounced effect.
      When dosed at quantities limited by toxicity, allyl acetate and allyl alcohol
      produce higher levels of urinary mercapturic acids than the minimally toxic dose
      of acrolein. This observation is likely due to biotransformation of allyl acetate
      and ally alcohol to acrolein that occurs after absorption and suggests that these
      chemicals are protoxicants that increase systemic exposure of acrolein. Increased
      systemic exposure to acrolein is likely responsible for the differences in
      hepatic toxicological profile observed with these chemicals.

PMID- 18817841
TI  - Estrogen formation in endometrial and cervix cancer cell lines: involvement of
      aromatase, steroid sulfatase and 17beta-hydroxysteroid dehydrogenases (types 1,
      5, 7 and 12).
AB  - The involvement of aromatase, steroid sulfatase (STS) and reductive 17beta
      hydroxysteroid dehydrogenases (17beta-HSDs) in the production of estrogens was
      determined in four cell lines of endometrial cancer (Ishikawa, HEC-1A, HEC-1B and
      RL-95) and one cell line of cervix cancer (Hela) in culture. After incubation
      with 4-androstene-3,17-dione (4-dione), there are no estrogens, estrone (E1) and
      estradiol (E2), detected suggesting that the pathway of aromatase is not
      important in these cell lines. In whole cells, the results show low percentages
      of transformation of estrone sulfate (E1S) into E1 suggesting that the entrance
      of E1S is difficult. However, in homogenized cells the STS activity was much
      higher and fully blocked by an inhibitor. Using selective inhibitors for each
      reductive 17beta-HSD (types 1, 5, 7 and 12), alone or in combination, we did not
      succeed in completely blocking the conversion of E1 into E2, suggesting that
      another 17beta-HSD (known or unknown) is involved in the formation of E2 from E1.

PMID- 18817842
TI  - Up-regulation of P2X7 receptor-immunoreactivity by in vitro ischemia on the
      plasma membrane of cultured rat cortical neurons.
AB  - Mixed neuronal/astrocytic cortical cell cultures of the rat were incubated for 2
      or 12h under normoxic or ischemic conditions. Subsequent flow cytometric analysis
      with an anti-P2X7 receptor antibody directed against an extracellular epitope
      indicated the up-regulation of these receptors at the plasma membrane by 12h of
      ischemia. Labelling of MAP-2 immunopositive neurons by an anti-P2X7 antibody
      directed against a C-terminal epitope, documented the selectivity of the ischemia
      induced increase in receptor-density for the neuronal population. By contrast,
      staining of GFAP immunopositive astrocytes by the same anti-P2X7 antibody
      excluded any effect of ischemia on the astrocytic density of P2X7 receptors. The
      ischemic up-regulation of neuronal P2X7 receptors is in perfect agreement with
      the previously reported facilitation of transmitter release from the GABAergic
      non-pyramidal cell type in such cultures [K. Wirkner, A. Kofalvi, W. Fischer, A.
      Gunther, H. Franke, H. Groger-Arndt, W. Norenberg, E. Madarasz, E.S. Vizi, D.
      Schneider, B. Sperlagh, P. Illes, Supersensitivity of P2X7 receptors in
      cerebrocortical cell cultures after in vitro ischemia, J. Neurochem. 95 (2005)
      1421-1437].

PMID- 18817843
TI  - Expression of Claudin-1, Claudin-3 and Claudin-5 in human blood-brain barrier
      mimicking cell line ECV304 is inducible by glioma-conditioned media.
AB  - Up to now no standard cell culture model of the blood-brain barrier is available.
      However, several models based on primary cells or continuous cell lines have been
      characterized and described in respect of different applications. One of the most
      important characteristics of the blood-brain barrier is the restriction of
      paracellular transport, respectively its tightness. Human cell line ECV304 is one
      of the promising continuous cell lines for blood-brain barrier modelling due to
      two reasons: on the one hand the cells are able to form significant tighter
      layers than most of the other cell lines used and on the other hand several
      properties of the blood-brain barrier are inducible by using glioma-conditioned
      medium. Claudins are transmembranal proteins which form the backbone of the tight
      junctions at the blood-brain barrier. We have investigated the presence and
      inducibility of the expression of Claudin-1, Claudin-3 and Claudin-5 using
      immunofluorescence microscopy. For the first time this study proves the presence
      of Claudin-1, Claudin-3 and Claudin-5 in ECV304 (obtained from ECACC) cell layers
      and the inducibility of their expression by glioma-conditioned media.

PMID- 18817844
TI  - Morphophysiologic properties of islet cells in substantia gelatinosa of the rat
      spinal cord.
AB  - Substantia gelatinosa (SG) neurons of the spinal cord are highly heterogeneous in
      their morphophysiologic properties and could be categorized on several subtypes.
      Here the properties of islet cells in rat SG (approximately 11%) are described
      with the use of confocal microscopy and patch-clamp recording. The cells had
      significantly longer and thicker dendritic trees among all other neurons. Only
      these cells expressed slow inward current activated by hyperpolarization, which
      could be blocked by Cs+ but not Ba2+, presumably representing H-current (Ih).
      Possibly due to Ih, islet cells had peculiar membrane and firing responses. Of
      note the membrane potential showed a sag in response to hyperpolarization while
      depolarization triggered action potentials (APs) in a tonic-like pattern. APs,
      however, occurred with larger maximal frequencies and in response to broader
      stimulation intensities than in other tonically firing neurons. Neuronal
      variability in SG and possible functional roles of islet cells are discussed.

PMID- 18817845
TI  - Effect of acute and chronic exercise on oxidant-antioxidant equilibrium in rat
      hippocampus, prefrontal cortex and striatum.
AB  - Although regular physical exercise is beneficial to the body, it is well known
      that exhaustive exercise causes oxidative stress in muscle. Recent studies
      suggest that regular moderate physical exercise has the beneficial effects on
      brain. There is a little information regarding whether or not exercise could
      generate oxidative stress in the brain and the findings are conflicting. The aim
      of this study was to investigate the effects of acute and chronic exercise on
      thiobarbituric acid reactive substances, as an indicator of lipid peroxidation,
      in the hippocampus, which has a high concentration of glucocorticoid receptors,
      and prefrontal cortex and striatum, which have high dopamine content.
      Additionally we examined antioxidant enzyme activities, superoxide dismutase and
      glutathione peroxidase and nitrite-nitrate levels to assess the effects of
      reactive oxygen and nitrogen species. In this study it was shown that acute
      treadmill exercise at different strengths did not cause oxidative stress in
      prefrontal cortex, striatum and hypocampus regions of the brain. Regular
      treadmill exercise performed at different strengths was shown not to cause
      oxidative stress in prefrontal cortex, striatum and hippocampus regions of brain.
      As a result, we propose that acute and chronic exercise do not cause oxidant
      stress in prefrontal cortex, striatum and hippocampus and chronic exercise has a
      favorable effect on hippocampus, possibly by decreasing superoxide radical
      formation.

PMID- 18817846
TI  - Reduced NGF level and TrkA protein and TrkA gene expression in the optic nerve of
      rats with experimentally induced glaucoma.
AB  - Glaucoma (GL) is an optic neuropathy characterized by progressive loss of visual
      field due to retinal cell death and optic nerve (ON) degeneration, usually in
      response to abnormal elevated intraocular pressure (EIOP). It has previously
      demonstrated that cells of the ON express nerve growth factor (NGF) and NGF
      receptors. Relatively little is known, however, about their role on the ON of the
      glaucomatous eye. The aim of the study was to elucidate this aspect. Using a rat
      model of GL we investigated the response of NGF and NGF-receptors in the ON of
      subjects with experimentally induced EIOP. Our results show that EIOP
      significantly impairs the presence of NGF and NGF-receptor proteins and TrkA gene
      expression in the ON of glaucomatous eye. These findings suggest that NGF and NGF
      receptor might be important signals for the ON response in the EIOP.

PMID- 18817847
TI  - Psychological prenatal stress reduced the number of BrdU immunopositive cells in
      the dorsal hippocampus without affecting the open field behavior of male and
      female rats at one month of age.
AB  - We examined whether prenatal psychological stress with little physical stress
      causes changes in the behavior and neurogenesis of the offspring of Sprague
      Dawley rats at one month. Dams in the last trimester of gestation were
      psychologically stressed by placing them in a social communication box and
      shocking a rat on the other side of a transparent wall. They suffered little
      physical stress. Male and female offspring from the dams showed little change in
      an open field test at postnatal day (PND) 30. To evaluate neurogenesis in the
      brain, BrdU was intraperitoneally injected at PND 35 into offspring not used in
      the open field test. Immunohistochemical examinations of BrdU in their dorsal
      hippocampus at PNDs 42 and 112 revealed that the number of BrdU immunopositive
      cells in the offspring of prenatally stressed rats was significantly smaller than
      in the offspring of unstressed ones. These results together with our previous
      finding that prenatal psychological stress can alter specific behaviors suggest
      that prenatal psychological stress can suppress neurogenesis in the dorsal
      hippocampus of rats of both sexes at PND 35 even though impairment in the
      behavioral task has not yet appeared.

PMID- 18817848
TI  - 3-Nitropropionic acid-induced depression of spinal reflexes does not involve 5
      hydroxytryptaminergic system in contrast to ischemia-induced depression in
      neonatal rat spinal cord in vitro.
AB  - The involvement of 5-hydroxytryptaminergic (5-HTergic) system for the 3
      nitropropionic acid (3-NPA)-induced depression of spinal reflexes was evaluated
      and compared with other energy deficiency condition (ischemia; glucose-free and
      O2-free). The monosynaptic (MSR) and polysynaptic reflex (PSR) potentials were
      recorded at ventral root by stimulating the corresponding dorsal root in neonatal
      rat spinal cord in vitro. Superfusion of 3-NPA (3.4 mM) or ischemic solution
      depressed the reflexes in a time-dependent manner abolishing them by 35 min.
      Pretreatment with pindolol (1 microM), ketanserin (10 microM) or ondansetron (0.1
      microM); 5-HT1, 5-HT2, or 5-HT3 receptor antagonist, respectively, did not block
      the 3-NPA-induced depression of reflexes whereas, ischemia-induced depression was
      blocked by ondansetron. 5-HT content of the spinal cords incubated with 3-NPA
      (3.4 mM) for 30 min was decreased significantly (33 ng/g tissue) while increased
      (286 ng/g) in cords exposed to ischemic solution as compared to saline-treated
      cords (161 ng/g). Thus, 3-NPA-induced depression of spinal reflexes does not
      involve 5-HTergic pathway unlike ischemia-induced depression.

PMID- 18817849
TI  - Timed restricted feeding restores the rhythms of expression of the clock protein,
      Period2, in the oval nucleus of the bed nucleus of the stria terminalis and
      central nucleus of the amygdala in adrenalectomized rats.
AB  - Feeding schedules that limit food availability to a set time of day are powerful
      synchronizers of the rhythms of expression of the circadian clock protein Period
      2 (PER2) in the limbic forebrain in rats. Little is known, however, about the
      mechanisms that mediate the effect of such timed restricted feeding (TRF)
      schedules on the expression of PER2. Adrenal glucocorticoids have been implicated
      in the circadian regulation of clock genes expression in peripheral tissues as
      well as in the control of the rhythms of expression of PER2 in certain limbic
      forebrain regions, such as the oval nucleus of the bed nucleus of the stria
      terminalis (BNSTov) and central nucleus of the amygdala (CEA) in rats. To study
      the possible involvement of glucocorticoids in the regulation of PER2 expression
      by TRF, we assessed the effect of adrenalectomy on TRF-entrained PER2 rhythms in
      the limbic forebrain in rats. Adrenalectomy selectively abolished the rhythms of
      PER2 in the BNSTov and CEA in normally fed rats, as previously shown, but had no
      effect on TRF-entrained PER2 rhythms in the same structures. These findings show
      that the effect of TRF on PER2 rhythms in the limbic forebrain is independent of
      adrenal glucocorticoids and demonstrate that the involvement of glucocorticoids
      in the regulation PER2 rhythms in the limbic forebrain is not only region
      specific, as previously shown, but also state dependent.

PMID- 18817850
TI  - An immunohistochemical study of the gonadotrophin-releasing hormone 1 system in
      solitary Cape mole-rats, Georychus capensis, and social Natal mole-rats,
      Cryptomys hottentotus natalensis.
AB  - Mole-rat species within the family Bathyergidae exhibit a wide range of
      reproductive strategies and social systems. Various forms of reproductive
      suppression are displayed within this family: in the solitary species, breeding
      is suspended for part of the year and in the social species, reproduction is
      suppressed in subordinate animals. This study investigated the gonadotrophin
      releasing hormone 1 (GnHR-1) systems of breeding and non-breeding solitary Cape
      mole-rats and social Natal mole-rats for possible inter- and/or intra-species
      differences. In both species, GnRH-1 cell bodies are predominantly in the medial
      septum region of the diagonal band or the preoptic area, with relatively few in
      the mediobasal hypothalamus; a dense concentration of GnRH-1-immunoreactive (ir)
      processes is present in the region of the organum vasculosum of the lamina
      terminalis. In Cape mole-rats, GnRH-1-ir processes are particularly dense within
      the lateral margins of the median eminence, which is enfolded by a large pars
      tuberalis of the pituitary gland. Natal mole-rats display GnRH-1-ir processes
      across the breadth of the median eminence, which is abutted by a relatively small
      pars tuberalis. There are more GnRH-1-ir cell bodies in Natal mole-rats than in
      Cape mole-rats ( approximately 720 vs. approximately 420). No significant
      differences were found in the number, distribution or size of GnRH-1-ir cell
      bodies according to season in Cape mole-rats or according to reproductive status
      or sex in Natal mole-rats. In female and male Natal mole-rats, GnRH-1
      immunoreactivity in the median eminence is less dense in the reproductive
      animals; no such difference was found in Cape mole-rats between the breeding and
      non-breeding seasons. These immunohistochemical results are discussed in the
      light of earlier studies which identified no functional neuroendocrine
      impediments underlying regulated reproduction in either Cape or Natal mole-rats.
      The cumulative findings suggest that the principal factors determining seasonal
      or socially induced suppression of reproduction in these species are behavioral
      rather than neuroendocrine.

PMID- 18817851
TI  - Emotional, cognitive and neurochemical alterations in a premotor stage model of
      Parkinson's disease.
AB  - In addition to classic motor symptoms, Parkinson's disease (PD) is characterized
      by cognitive and emotional deficits, which have been demonstrated to precede
      motor impairments. The present study addresses the question of whether a partial
      degeneration of dopaminergic neurons using 6-hydroxydopamine (6-OHDA) in rats is
      able to induce premotor behavioral signs. The time-course of nigrostriatal damage
      was evaluated by tyrosine hydroxylase immunohistochemistry and the levels of
      dopamine, noradrenaline, and 5-HT in various brain regions were analyzed by high
      performance liquid chromatography (HPLC). Behavioral tests that assessed a
      variety of psychological functions, including locomotor activity, emotional
      reactivity and depression, anxiety and memory were conducted on 6-OHDA lesioned
      rats. Bilateral infusion of 6-OHDA in the striatum of rats caused early (1 week)
      damage of dopaminergic terminals in striatum and in cell bodies in substantia
      nigra pars compacta. The nigrostriatal lesion was accompanied by early loss of
      dopamine in the striatum, which remained stable through a 3-week period of
      observation. In addition, a late (3 weeks) loss of dopamine in the prefrontal
      cortex, but not in the hippocampus, was seen. Additional noradrenergic and
      serotonergic alterations were observed after 6-OHDA administration. The results
      indicated that 6-OHDA lesioned rats show decreased sucrose consumption and an
      increased immobility time in the forced swimming test, an anhedonic-depressive
      like effect. In addition, an anxiogenic-like activity in the elevated plus maze
      test and cognitive impairments were observed on the cued version of the Morris
      water maze and social recognition tests. These findings suggest that partial
      striatal dopaminergic degeneration and parallel dopaminergic, noradrenergic and
      serotonergic alterations in striatum and prefrontal cortex may have caused the
      emotional and cognitive deficits observed in this rat model of early phase PD.

PMID- 18817852
TI  - Unilateral axonal or terminal injection of 6-hydroxydopamine causes rapid-onset
      nigrostriatal degeneration and contralateral motor impairments in the rat.
AB  - Unilateral injection of the catecholamine neurotoxin 6-hydroxydopamine into the
      axons or terminals of the nigrostriatal pathway is commonly used to model
      Parkinson's disease in experimental animals. Although the terminal lesion
      paradigm is considered to induce a more progressive lesion when compared to the
      axonal lesion, few studies have directly compared the early time-course for
      lesion development in these two models. Thus, this experiment sought to establish
      the temporal pattern of nigrostriatal degeneration and emergence of contralateral
      motor impairment in these models. Young adult male Lister Hooded rats were used.
      After baseline testing on a battery of spontaneous motor tests, standard
      stereotaxic techniques were used to inject 6-hydroxydopamine into the
      nigrostriatal axons or terminals at the level of the medial forebrain bundle or
      striatum respectively. From the day after lesion surgery, a subset of the rats
      was tested for motor performance, while another subset was used for
      immunohistochemical analysis. Quantitative tyrosine hydroxylase
      immunohistochemistry revealed that although both lesions caused a similar
      temporal pattern of immunopositive cell loss from the substantia nigra, the
      terminal lesion caused a more rapid loss of immunopositive terminals from the
      striatum. Despite these differences in striatal dopaminergic deafferentation,
      both lesion types caused a profound loss of contralateral motor function from the
      first day after lesion surgery. These findings illustrate the rapidity of the
      neuropathological and behavioural consequences of either axonal or terminal
      injection of 6-hydroxydopamine into the nigrostriatal pathway, and further
      highlight the need for a more progressive model of human Parkinson's disease.

PMID- 18817853
TI  - Cerebral neurons involved in the innervation of both the adrenal gland and the
      ovary: a double viral tracing study.
AB  - Previous studies using the viral transneuronal tracing technique demonstrated
      central autonomic circuits involved in the innervation of the adrenal gland and
      the ovary. Since the pattern of infection of central nervous system structures is
      similar after virus inoculation of the adrenal gland and the ovary, and, on the
      other hand, it is well documented that the activity of the hypothalamo-pituitary
      adrenal axis exerts an inhibitory effect on the reproductive system, we
      investigated whether there are neurons that are transneuronally connected both
      with the adrenal gland and the ovary. The central circuitry involved in the
      innervation of the left adrenal and the left ovary was studied in individual rats
      by dual transneuronal tracing using isogenic recombinant strains (BDG and DS-RED)
      of Bartha strain of pseudorabies virus. Dual-infected neurons were detected in
      the ventrolateral medulla, nucleus of the solitary tract, caudal raphe nuclei, A5
      cell group, and hypothalamic paraventricular nucleus. The results indicate that
      there are neurons in the central nervous system that contribute to the
      transneuronal innervation of both the adrenal gland and the ovary. The data
      suggest a new type of interaction, i.e. interaction at cellular level that might
      be involved in regulatory processes integrating the functional activity of the
      two organs.

PMID- 18817854
TI  - Persistent behavioral alterations in rats neonatally exposed to low doses of the
      organophosphate pesticide, parathion.
AB  - Although developmental exposures of rats to low levels of the organophosphate
      pesticides (OPs), chlorpyrifos (CPF) or diazinon (DZN), both cause persistent
      neurobehavioral effects, there are important differences in their neurotoxicity.
      The current study extended investigation to parathion (PTN), an OP that has
      higher systemic toxicity than either CPF or DZN. We gave PTN on postnatal days
      (PND) 1-4 at doses spanning the threshold for systemic toxicity (0, 0.1 or 0.2
      mg/kg/day, s.c.) and performed a battery of emotional and cognitive behavioral
      tests in adolescence through adulthood. The higher PTN dose increased time spent
      on the open arms and the number of center crossings in the plus maze, indicating
      greater risk-taking and overall activity. This group also showed a decrease in
      tactile startle response without altering prepulse inhibition, indicating a
      blunted acute sensorimotor reaction without alteration in sensorimotor
      plasticity. T-maze spontaneous alternation, novelty-suppressed feeding,
      preference for sweetened chocolate milk, and locomotor activity were not
      significantly affected by neonatal PTN exposure. During radial-arm maze
      acquisition, rats given the lower PTN dose committed fewer errors compared to
      controls and displayed lower sensitivity to the amnestic effects of the NMDA
      receptor blocker, dizocilpine. No PTN effects were observed with regard to the
      sensitivity to blockade of muscarinic and nicotinic cholinergic receptors, or
      serotonin 5HT(2) receptors. This study shows that neonatal PTN exposure evokes
      long-term changes in behavior, but the effects are less severe, and in some
      incidences opposite in nature, to those seen earlier for CPF or DZN, findings
      consistent with our neurochemical studies showing different patterns of effects
      and less neurotoxic damage with PTN. Our results reinforce the conclusion that
      low dose exposure to different OPs can have quite different neurotoxic effects,
      obviously unconnected to their shared property as cholinesterase inhibitors.

PMID- 18817855
TI  - Enhancement of prostaglandin D(2) production through cyclooxygenase-2 and
      lipocalin-type prostaglandin D synthase by upstream stimulatory factor 1 in human
      brain-derived TE671 cells under serum starvation.
AB  - We found that prostaglandin (PG) D(2) production was induced through
      transcriptional activation of cyclooxygenase (COX)-2 and lipocalin-type PGD
      synthase (L-PGDS) genes under serum-starved conditions in human brain-derived
      TE671 cells. Analysis of promoter and intron regions of the human L-PGDS gene
      demonstrated that an atypical E-box within intron 4 mediated serum starvation
      induced up-regulation of L-PGDS gene expression. The results of electrophoretic
      mobility shift assay and chromatin immunoprecipitation assay showed that upstream
      stimulatory factor (USF) 1 bound to this atypical E-box. USF1 gene expression was
      also enhanced during serum starvation in TE671 cells through activation of p38
      mitogen activated protein kinase, and the efficiency of the binding of USF1 to
      the atypical E-box was clearly increased by serum starvation. Administration of
      USF1 siRNA suppressed both L-PGDS and COX-2 gene expression and PGD(2)
      production. Moreover, NS-398, a COX-2 inhibitor and AT-56, an L-PGDS inhibitor,
      suppressed PGD(2) production in TE671 cells cultured under the serum-starved
      condition. These results indicate that PGD(2) production stimulated by serum
      starvation is mediated by both COX-2 and L-PGDS through enhancement of USF1 in
      TE671 cells.

PMID- 18817856
TI  - Accelerated evolution of small serum proteins (SSPs)-The PSP94 family proteins in
      a Japanese viper.
AB  - Five small serum proteins (SSPs) with molecular masses of 6.5-10 kDa were
      detected in Habu (Trimeresurus flavoviridis) serum; this included two novel
      proteins SSP-4 and SSP-5. The amino acid sequences of these proteins and of SSP
      1, SSP-2, and SSP-3, which were reported previously, were determined on the basis
      of the nucleotide sequences of their cDNAs. Although these proteins exhibited
      only limited sequence identity to mammalian prostatic secretory protein of 94
      amino acids (PSP94), the topological pattern of disulfide bonds in SSPs was
      identical to that of the mammalian proteins. SSP-3 and SSP-4 lacked approximately
      30 residues at the C-terminal. Each of the full-length cDNAs encoded a mature
      protein of 62-90 residues and a highly conserved signal peptide. The evolutionary
      distances between SSPs estimated on the basis of the amino acid changes were
      significantly greater than those of the synonymous nucleotide substitutions;
      these finding, together with results from analyses of nonsynonymous to synonymous
      rates of change (dN/dS) suggest that snake SSPs have endured substantial
      accelerated adaptive protein evolution. Such accelerated positive selection in
      SSPs parallels other findings of similar molecular evolution in snake venom
      proteins and suggests that diversifying selection on both systems may be linked,
      and that snake SSP genes may have evolved by gene duplication and rapid
      diversification to facilitate the acquisition of various functions to block venom
      activity within venomous snakes.

PMID- 18817857
TI  - Comparative analysis of Xenopus tropicalis hepcidin I and hepcidin II genes.
AB  - Hepcidin is an antimicrobial peptide and an iron-regulatory hormone that is
      conserved in fish, amphibians, and mammalians. Here we report the genomic and
      biochemical characterization of two amphibian hepcidins (tHEP1 and tHEP2) from
      the Western clawed frog (Xenopus tropicalis). Similar to fish and mammalian
      hepcidins, both tHEP1 and tHEP2 genes contain three exons and two introns. The
      predicted mature tHEP1 and tHEP2 hepcidins are a 25 amino acid peptide and a 24
      amino acid peptide, respectively. Both tHEP1 and tHEP2 are strongly expressed in
      the liver and kidney, with detectable expression in the heart. In addition, tHEP2
      is also moderately expressed in the stomach and testis. The expression of tHEP2
      (but not tHEP1) in the liver is strongly induced by iron overloading, while the
      expression of tHEP1 (but not tHEP2) in the liver is significantly inhibited by
      corticosterone. Genomic analysis of the promoter regions of these two frog
      hepcidin genes indicates that transcription regulation factors NF-kappaB and
      C/EBPbeta may be involved in hepcidin regulation by iron. Hence, X. tropicalis is
      a useful model for the study of molecular evolution, transcriptional regulation,
      and structure-activity relationships of vertebrate hepcidins.

PMID- 18817858
TI  - Computational search for over-represented 8-mers within the 5'-regulatory regions
      of 634 mouse testis-specific genes.
AB  - Accumulation of microarray data has enabled the computational analysis of gene
      expressions in various tissues. Although the genes showing testis-specific
      expression are most abundant among the genes exhibiting tissue-specific
      expression, no systematic study has been conducted for over-represented motifs
      within their regulatory regions. We have identified 117 over-represented 8-mers
      that appeared 2648 times within the regulatory regions of 634 testis-specific
      genes. Of these, 64 over-represented 8-mers were significantly more frequent in
      the regulatory regions of testis-specific genes than in those of non-testis
      specific genes. In this group of 8-mers, 4 8-mers differed from the canonical
      cAMP response element (CRE) 8-mer by 1 letter, but the canonical CRE was not
      included in this group. We consider that CRE-like 8-mers participate in the
      regulatory expression of testis-specific genes to a greater extent than the
      canonical CRE 8-mer.

PMID- 18817859
TI  - Identification of new up-regulated genes under drought stress in soybean nodules.
AB  - Legumes/rhizobium biological N(2) fixation (BNF) is dramatically affected under
      abiotic stress such as drought, salt, cold and heavy metal stresses. Nodule
      response to drought stress at the molecular level was analysed using soybean
      (Glycine max) and Bradyrhizobium japonicum as a model, since this symbiotic
      partnership is extremely sensitive to this stress. To gain insight into molecular
      mechanisms involved in drought-induced BNF inhibition, we have constructed a SSH
      (Suppression Subtractive Hybridisation) cDNA library from nodular tissue of
      plants irrigated at field capacity or plants water deprived for 5 days. Sequence
      analysis of the first set of 128 non redundant ESTs using protein databases and
      the Blastx program indicated that 70% of ESTs could be classified into putative
      known functions. Using reverse northern hybridization, 56 ESTs were validated as
      up-regulated genes in response to drought. Interestingly, only a few of them had
      been previously described as involved in plant response to drought, therefore
      most of the ESTs could be considered as new markers of drought stress. Here we
      discuss the potential role of some of these up-regulated genes in response to
      drought. Our analysis focused on two genes, encoding respectively a ferritin and
      a metallothionein, which are known to be involved in homeostasis and
      detoxification of metals and in response to oxidative stress. Their
      spatiotemporal expression patterns showed a high accumulation of transcripts
      restricted to infected cells of nodules in response to drought.

PMID- 18817860
TI  - Involvement of platelet-derived growth factor receptor-beta in maintenance of
      mesenchyme and sensory epithelium of the neonatal mouse inner ear.
AB  - Platelet-derived growth factor receptor (PDGFR) signaling has been demonstrated
      to play a pivotal role in early embryonic development. Although the expression of
      PDGF in the inner ear has been studied by RT-PCR, how PDGFR is involved there
      remains largely unclear. In the current study, we used the antagonistic anti
      PDGFR-beta antibody, APB5, to investigate the role of PDGFR-beta in the neonatal
      mouse inner ear. PDGFR-beta was detected immunohistochemically in the mesenchymal
      tissue adjacent to the sensory epithelium of the inner ear, and a ligand for
      PDGFR-beta was detected around the sensory epithelium. To determine whether this
      expression plays a functional role, we injected APB5 into neonates to block the
      function of PDGFR-beta. Mesenchymal tissue defects and abnormal capillaries with
      irregular shapes, especially in the cochlear lateral wall, were detected in APB5
      treated mice. The results of a TUNEL assay revealed that not only the adjacent
      mesenchymal cells but also the sensory epithelial cells underwent cell death.
      These results indicate that PDGFR-beta signals are required for the survival of
      the capillary and mesenchymal cells in the neonatal mouse inner ear and also
      indirectly implicate these signals in the survival of the sensory epithelium.

PMID- 18817861
TI  - Neural tonotopy in cochlear implants: an evaluation in unilateral cochlear
      implant patients with unilateral deafness and tinnitus.
AB  - In cochlear implants, the signal is filtered into different frequency bands and
      transmitted to electrodes along the cochlea. In this study the frequency-place
      function for electric hearing was investigated as a means to possibly improve
      speech coding by delivering information to the appropriate cochlear place.
      Fourteen subjects with functional hearing in the contralateral ear have been
      provided with a MED-EL cochlear implant in the deaf ear in order to reduce
      intractable tinnitus. Pitch scaling experiments were performed using single
      electrode, constant-amplitude, constant-rate stimuli in the implanted ear, and
      acoustic sinusoids in the contralateral ear. The frequency-place function was
      calculated using the electrode position in the cochlea as obtained from
      postoperative skull radiographs. Individual frequency-place functions were
      compared to Greenwood's function in normal hearing. Electric stimulation elicited
      a low pitch in the apical region of the cochlea, and shifting the stimulating
      electrode towards the basal region elicited increasingly higher pitch. The
      frequency-place function did not show a significant shift relative to Greenwood's
      function. In cochlear implant patients with functional hearing in the non
      implanted ear, electrical stimulation produced a frequency-place function that on
      average resembles Greenwood's function. These results differ from previously
      derived data.

PMID- 18817862
TI  - Protective effects of butanol fraction from Betula platyphyla var. japonica on
      cartilage alterations in a rabbit collagenase-induced osteoarthritis.
AB  - AIM OF THIS STUDY: Many cartilage protective agents have been developed from
      natural products, and they have resulted in the development of treatments for
      osteoarthritis. In this study, we determined the osteoarthritic efficacy and
      mechanism of butanol fraction from the bark of Betula platyphylla var. japonica
      (BFBP) in collagenase-induced rabbit model of osteoarthritis (CIA). MATERIALS AND
      METHODS: The right knees of rabbits were injected intra-articularly with
      collagenase, and rabbits were orally administrated with distilled water
      (vehicle), BFBP (50, 100 and 200 mg/kg) or celecoxib (100 mg/kg) once a day for
      28 days after the initiation of the CIA. RESULTS: Oral administration of BFBP
      dose-dependently suppressed the stiffness and global histologic score.
      Proteoglycan intensity was considerably increased in a dose-dependent manner. As
      well, the mRNA expression of MMP-1, and MMP-3 was decreased. On the contrary, the
      level of TIMP-1 in the synovial fluids was significantly increased in the BFBP
      treated group. The pathologic inflammatory molecules such as PGE2 and COX-2 were
      inhibited by BFBP, but COX-1 expression not affected. CONCLUSION: We suggest that
      BFBP has shown the protective effect on cartilage alternations through balance of
      MMPs/TIMP-1 and regulates inflammatory-related molecules in vivo model of
      osteoarthritis, and great candidate for development of osteoarthritis treatment.

PMID- 18817863
TI  - Alterations of activity and intracellular distribution of the 20S proteasome in
      ageing retinal pigment epithelial cells.
AB  - Age-related macular degeneration (AMD) remains high incidence and accounts for a
      main cause of blindness in ageing people, but its mechanism is still poorly
      understood. Ageing and associated dysfunction of retinal pigment epithelial (RPE)
      cells were believed to be the pathological onset of AMD. 20S proteasome has been
      tightly correlated with cell ageing due to its fundamental role in maintaining
      cellular homeostasis, but its implication in the ageing process of human RPE
      cells was seldom concerned. This study aimed to demonstrate the interconnections
      between 20S proteasome and ageing RPE cells by characterizing age-dependent
      alterations of the 20S proteasome in primarily cultured human RPE cells. For this
      purpose, a replicative ageing RPE cell model was established and validated
      through testing the cell viability, beta-galactosidase activity and cellular
      autofluorescence. Decline in chymotrypsin-like, peptidylglutamyl-peptide
      hydrolase and trypsin-like activities of the 20S proteasome was detected in aged
      RPE cells through degradation of fluorogenic substrates. Immunofluorescence assay
      revealed that the 20S proteasome was concentrated in RPE nucleus, and
      redistributed partly to the peri-nuclear regions in old RPE passages. These age
      dependent changes of the 20S complex were accompanied with a significantly
      increased fluorescent intensity of intracellular oxidized proteins. Further
      analysis of the proteasome-to-oxidized protein ratio indicated a preferred
      protection of the RPE nuclear proteins by the 20S proteasome, which also subsided
      remarkably as a function of the cell ageing. In conclusion, we demonstrated
      functional impairment and redistribution of the 20S proteasome with age in human
      RPE cells and supposed these alterations impactful on the process of RPE cell
      ageing and furthermore on the pathogenesis of AMD. Future researches on the
      mechanism of these alterations and the pathways to manipulate their effects are
      still strongly recommended.

PMID- 18817864
TI  - Determining the influence of telomere dysfunction and DNA damage on stem and
      progenitor cell aging: what markers can we use?
AB  - The decline in organ maintenance and function is one of the major problems
      limiting quality of life during aging. The accumulation of telomere dysfunction
      and DNA damage appears to be one of the underlying causes. Uncapping of
      chromosome ends in response to critical telomere shortening limits the
      proliferative capacity of human cells by activation of DNA damage checkpoints
      inducing senescence or apoptosis. Telomere shortening occurs in the vast majority
      of human tissues during aging and in chronic diseases that increase the rate of
      cell turnover. There is emerging evidence that telomere shortening can limit the
      maintenance and function of adult stem cells -- a cell type of utmost importance
      for organ maintenance and regeneration. In mouse models, telomere dysfunction
      leads to a depletion of adult stem cell compartments suggesting that stem cells
      are very sensitive to DNA damage. Both the rarity of stem and progenitor cells in
      adult organs and their removal in response to damage make it difficult to assess
      the impact of telomere dysfunction and DNA damage on stem and progenitor cell
      aging. Such approaches require the development of sensitive biomarkers
      recognizing low levels of telomere dysfunction and DNA damage in stem and
      progenitor cells. Here, we review experimental data on the prevalence of telomere
      dysfunction and DNA damage during aging and its possible impact on stem and
      progenitor cell aging.

PMID- 18817865
TI  - Proteome-wide prediction of PKA phosphorylation sites in eukaryotic kingdom.
AB  - Protein phosphorylation is one of the most essential post-translational
      modifications (PTMs), and orchestrates a variety of cellular functions and
      processes. Besides experimental studies, numerous computational predictors
      implemented in various algorithms have been developed for phosphorylation sites
      prediction. However, large-scale predictions of kinase-specific phosphorylation
      sites have not been successfully pursued and remained to be a great challenge. In
      this work, we raised a "kiss farewell" model and conducted a high-throughput
      prediction of cAMP-dependent kinase (PKA) phosphorylation sites. Since a protein
      kinase (PK) should at least "kiss" its substrates and then run away, we proposed
      a PKA-binding protein to be a potential PKA substrate if at least one PKA site
      was predicted. To improve the prediction specificity, we reduced false positive
      rate (FPR) less than 1% when the cut-off value was set as 4. Successfully, we
      predicted 1387, 630, 568 and 912 potential PKA sites from 410, 217, 173 and 260
      PKA-interacting proteins in Saccharomyces cerevisiae, Caenorhabditis elegans,
      Drosophila melanogaster and Homo sapiens, respectively. Most of these potential
      phosphorylation sites remained to be experimentally verified. In addition, we
      detected two sites in one of PKA regulatory subunits to be conserved in
      eukaryotes as potentially ancient regulatory signals. Our prediction results
      provide an excellent resource for delineating PKA-mediated signaling pathways and
      their system integration underlying cellular dynamics and plasticity.

PMID- 18817866
TI  - A combination of Lox-1 and Nox1 regulates TLR9-mediated foam cell formation.
AB  - The formation of foam cells is the hallmark of early atherosclerotic lesions, and
      the uptake of modified low-density lipoprotein (LDL) by macrophage scavenger
      receptors is thought to be a key process in their formation. In this study, we
      examined the role of lectin-like oxLDL receptor-1 (Lox-1) and NADPH oxidase 1
      (Nox1) in toll-like receptor 9 (TLR9)-mediated foam cell formation. TLR9
      activation of Raw264.7 cells or mouse primary peritoneal macrophages by CpG ODN
      treatment enhanced Lox-1 gene and protein expression. In addition, CpG ODN
      induced Nox1 mRNA expression, which in turn increased foam cell formation. The
      inhibition of CpG ODN-induced reactive oxygen species (ROS) generation by
      treatment with antioxidants, as well as with knockdown of Nox1 using siRNA,
      suppressed the formation of foam cells. The induction of Lox-1 and Nox1 by CpG
      ODN was regulated via the TLR9-p38 MAPK signaling pathway. CpG ODN also increased
      NFkappaB activity, and a potent inhibitor of NFkappaB that significantly blocked
      CpG-induced Nox1 expression, suggesting that Nox1 regulation is mediated through
      an NFkappaB-dependent mechanism. Taken together, these results suggest that a
      combination of Lox-1 and Nox1 plays a key role in the TLR9-mediated formation of
      foam cells via the p38 MAPK pathway.

PMID- 18817867
TI  - Bmi1 promotes prostate tumorigenesis via inhibiting p16(INK4A) and p14(ARF)
      expression.
AB  - We report here that the polycomb group protein Bmi1 promotes prostate
      tumorigenesis. Bmi1 is detected at higher levels in androgen-independent PC3 and
      DU145 than in androgen-dependent LNCaP prostate cancer (CaP) cells. Ectopic Bmi1
      enhanced the expression of human telomerase reverse transcriptase (hTERT) and
      suppressed the exression of p16(INK4A) and p14(ARF) in CaP cells. Consistent with
      these observations, immunohistochemical staining of 51 cases of primary CaP
      specimens revealed 1.4 fold (p=0.014) and 1.3 fold (p=0.051) higher levels of
      Bmi1-positive cells in carcinoma compared to normal prostatic epithelial cells
      and PIN, respectively. In primary CaPs, Bmi1 expression was associated with a
      reduction in p16(INK4A) and p14(ARF). Furthermore, in comparison to empty vector
      transfected cells, Bmi1-expressing DU145 cells formed significantly larger tumors
      in NOD/SCID mice. Taken together, we demonstrate that Bmi1 promotes prostate
      tumorigenesis.

PMID- 18817868
TI  - Ubiquitin and ubiquitin-like specific proteases targeted by infectious pathogens:
      Emerging patterns and molecular principles.
AB  - Attachment of ubiquitin (Ub) or ubiquitin-like (Ubl) modifiers is a reversible
      post-translational modification that regulates the fate and function of proteins.
      In particular, proteolytic enzymes with Ub/Ubl processing activity appear to be
      more widespread than originally anticipated. It is therefore not surprising that
      bacterial and viral pathogens have exploited many ways to interfere with Ub/Ubl
      conjugation, but also de-conjugation. On one hand, pathogens were shown to
      manipulate host encoded enzymes. On the other hand, pathogen derived sequences of
      proteases specific for Ub/Ubls are emerging as a common feature shared by many
      viruses, bacteria and protozoa, and we are at an early stage of understanding how
      these proteases contribute to the pathogenesis of infection. Whereas some of
      these proteases share a common origin with mammalian cell encoded hydrolases with
      specific properties towards Ub/Ubls, most of them have ancient intrinsic
      functions, such as processing pathogen protein components, and may have acquired
      the specificity for Ub/Ubls by interacting with mammalian hosts and their immune
      system throughout evolution. Since many of these proteases are clearly distinct
      from their mammalian counterparts, they represent attractive targets for drug
      design against infectious diseases.

PMID- 18817869
TI  - Theme issue "Solid state and solid dosage forms".

PMID- 18817870
TI  - Prevention of calcineurin inhibitor nephrotoxicity in renal transplantation.
AB  - Calcineurin inhibitors (CNI) cyclosporine (Csa) and tacrolimus (Tac) are now
      first intention immunosuppressive drugs in renal transplantation. However,
      although these treatments are effective for preventing allograft rejection, they
      are nephrotoxic: they can cause chronic renal dysfunction and degradation of
      renal graft function [Nankivell BJ, et al. The natural history of chronic
      allograft nephropathy. N Engl J Med. 2003 Dec 11;349(24):2326-33]. In view of
      these undesirable effects, several strategies have been developed to minimize or
      even avoid their use. These strategies are reviewed and discussed in this paper.

PMID- 18817871
TI  - Effect of recipient age on the outcome of kidney transplantation.
AB  - We investigated the effect of recipient age (RA) on kidney transplantation
      outcome in 107 transplant patients, with a follow-up of 1 year. Patients were
      divided in 3 groups: Group A (RA<50 years; 72 patients), Group B (RA 50-60 years,
      19 patients), and Group C (RA>60 years; 16 patients). The rate and severity of
      acute rejection, infection rate and type, delayed graft function, hospital stay,
      creatinine levels (3, 6, 12 months), incidence at 1 year of post-transplant
      hypertension, cholesterol and triglycerides blood levels, and the rate of post
      transplant surgical complications, and 1-year graft and patient survival were
      comparable between the 3 groups. However, creatinine blood level at 1 month and
      the 1-year fasting blood sugar were significantly higher in Group B. The RA does
      not seem to be of a significant predictive value, good selection and pre
      transplant patient workout are important factors for a better outcome.

PMID- 18817872
TI  - Mutant SOD1 from spinal cord of G93A rats is destabilized and binds to inner
      mitochondrial membrane.
AB  - Mutations in Cu/Zn superoxide dismutase (SOD1) cause amyotrophic lateral
      sclerosis (ALS). Mechanisms of mutant SOD1 toxicity are unknown, but increased
      SOD1 activity can boost production of reactive oxygen species (ROS) in the
      mitochondrial intermembrane space (IMS). Using non-reducing SDS-PAGE we found
      that in G93A-SOD1 rats the mutant SOD1 was prominently destabilized only in the
      diseased spinal cord, where this mutant enzyme was also up regulated in the IMS
      with increased ability to bind the inner membrane of isolated non-transgenic
      mitoplasts. These mitoplasts increased ROS production when exposed to mutant SOD1
      from the spinal cord at the presymptomatic stage. The levels of disulfide-reduced
      SOD1 peaked at the end stage of the disease, whereas protein disulfide isomerase
      (PDI), a chaperone capable of rearranging disulfide bonds between cysteine
      residues of SOD1, was increased prior to the end stage. IMS binding and increased
      ROS production by destabilized SOD1 may contribute to mitochondrial damage in
      G93A-SOD1 rats.

PMID- 18817873
TI  - Vesicular trafficking and secretion of matrix metalloproteinases-2, -9 and tissue
      inhibitor of metalloproteinases-1 in neuronal cells.
AB  - Matrix metalloproteinases (MMPs) are endopeptidases that cleave matrix, soluble
      and membrane-bound proteins and are regulated by their endogenous inhibitors the
      tissue inhibitors of MMPs (TIMPs). Nothing is known about MMP/TIMP trafficking
      and secretion in neuronal cells. We focussed our attention on the gelatinases MMP
      2 and MMP-9, and their inhibitor TIMP-1. MMPs and TIMP-1 fused to GFP were
      expressed in N2a neuroblastoma and primary neuronal cells to study trafficking
      and secretion using real time video-microscopy, imaging, electron microscopy and
      biochemical approaches. We show that MMPs and TIMP-1 are secreted in 160-200 nm
      vesicles in a Golgi-dependent pathway. These vesicles distribute along
      microtubules and microfilaments, co-localise differentially with the molecular
      motors kinesin and myosin Va and undergo both anterograde and retrograde
      trafficking. MMP-9 retrograde transport involves the dynein/dynactin molecular
      motor. In hippocampal neurons, MMP-2 and MMP-9 vesicles are preferentially
      distributed in the somato-dendritic compartment and are found in dendritic
      spines. Non-transfected hippocampal neurons also demonstrate vesicular secretion
      of MMP-2 in both its pro- and active forms and gelatinolytic activity localised
      within dendritic spines. Our results show differential trafficking of MMP and
      TIMP-1-containing vesicles in neuronal cells and suggest that these vesicles
      could play a role in neuronal and synaptic plasticity.

PMID- 18817874
TI  - MMPs initiate Schwann cell-mediated MBP degradation and mechanical nociception
      after nerve damage.
AB  - Matrix metalloproteinases (MMPs) emerge as modulators of neuropathic pain.
      Because myelin protects Abeta afferents from ectopic hyperexcitability and
      nociception from innocuous mechanical stimuli (or mechanical allodynia), we
      analyzed the role of MMPs in the development of mechanical allodynia through
      myelin protein degradation after rat and MMP-9-/- mouse L5 spinal nerve crush (L5
      SNC). MMPs were shown to promote selective degradation of myelin basic protein
      (MBP), with MMP-9 regulating initial Schwann cell-mediated MBP processing after
      L5 SNC. Acute and long-term therapy with GM6001 (broad-spectrum MMP inhibitor)
      protected from injury-induced MBP degradation, caspase-mediated apoptosis,
      macrophage infiltration in the spinal nerve and inhibited astrocyte activation in
      the spinal cord. The effect of GM6001 therapy on attenuation of mechanical
      allodynia was robust, immediate and sustained through the course of L5 SNC. In
      conclusion, MMPs mediate the initiation and maintenance of mechanical nociception
      through Schwann cell-mediated MBP processing and support of neuroinflammation.

PMID- 18817875
TI  - High-level expression of active recombinant ubiquitin carboxyl-terminal hydrolase
      of Drosophila melanogaster in Pichia pastoris.
AB  - Ubiquitin carboxyl-terminal hydrolases (UCHs) are implicated in the proteolytic
      processing of polymeric ubiquitin. The high specificity for the recognition site
      makes UCHs useful enzymes for in vitro cleavage of ubiquitin fusion proteins. In
      this work, an active C-terminal His-tagged UCH from Drosophila melanogaster
      (DmUCH) was produced as a secretory form in a recombinant strain of the
      methylotrophic yeast Pichia pastoris. The production of recombinant DmUCH by
      Mut(s) strain was much higher than that by Mut(+) strain, which was confirmed by
      Western blot analysis. When expression was induced at pH 6.0 in a BMMY/methanol
      medium, the concentration of recombinant DmUCH reached 210 mg l(-1). With the
      (His)(6)-tag, the recombinant DmUCH was easily purified by Ni-NTA chromatography
      and 18 mg pure active DmUCH were obtained from 100ml culture broth supernatant.
      Ubiquitin-magainin fusion protein was efficiently cleaved by DmUCH, yielding
      recombinant magainin with high antimicrobial activity. After removing the
      contaminants by Ni-NTA chromatography, recombinant magainin was purified to
      homogeneity easily by reversed-phase HPLC. Analysis of the recombinant magainin
      by ESI-MS showed that the molecular weight of the purified recombinant magainin
      was 2465 Da, which perfectly matches the mass calculated from the amino acid
      sequence. The result of mass spectrometry confirmed that the purified His-tagged
      DmUCH can recognize the ubiquitin-magainin fusion protein and cleave it at the
      carboxyl terminus of ubiquitin precisely. Our results showed that P. pastoris is
      a robust system to express the secreted form of DmUCH.

PMID- 18817876
TI  - cDNA cloning, characterization and mRNA expression of a pacifastin light chain
      gene from the Chinese mitten crab Eriocheir sinensis.
AB  - The pacifastin family, characterized by several conserved arrays of six cysteine
      residues, is a newly identified serine protease inhibitor (SPI) family discovered
      uniquely in arthropods and plays important roles in multiple biological
      processes. In the present study, the full-length cDNA of a pacifastin light chain
      (designated ESPLC) was cloned from the Chinese mitten crab Eriocheir sinensis by
      expressed sequence tags (ESTs) and PCR techniques. The 1036bp ESPLC cDNA
      contained an 831bp open reading frame (ORF) encoding a putative pacifastin
      related peptide of 276 amino acids, a 5'-untranslated region (UTR) of 67bp, and a
      3'-UTR of 138bp. Six putative conserved domains sharing a characteristic cysteine
      array (Cys-Xaa(9-12)-Cys-Asn-Xaa-Cys-Xaa-Cys-Xaa(2-3)-Gly-Xaa(3-4)-Cys-Thr-Xaa(3)
      Cys) were identified in the deduced amino acid sequence of ESPLC. The
      conservation of these PLDs (pacifastin light chain domains) and the relative
      higher similarity of ESPLC to other pacifastin-related precursors suggested that
      ESPLC was a member of pacifastin family. The mRNA transcripts of ESPLC were found
      to be higher expressed in hepatopancreas, gill and haemolymph than in gonad,
      muscle and heart, with the highest expression level in hepatopancreas. The ESPLC
      mRNA expression in haemolymph of Chinese mitten crab was up-regulated at 2h and
      12h after challenged with Listonella anguillarum. The tissue distribution and
      temporal characteristics of ESPLC mRNA expression, similar to that of
      prophenoloxidase gene in E. sinensis, suggested that ESPLC was potentially
      involved in the response against invading bacteria, with the possibility that it
      functioned in the prophenoloxidase system in E. sinensis.

PMID- 18817877
TI  - A serpin from Chinese shrimp Fenneropenaeus chinensis is responsive to bacteria
      and WSSV challenge.
AB  - Arthropod defence responses (e.g. prophenoloxidase (proPO) activation and Toll
      pathway initiation) are mediated by serine proteinase cascades and regulated by
      serpins in haemolymph. A serpin (Fc-serpin) cDNA was cloned from the haemocytes
      of Fenneropenaeus chinensis by rapid amplification of cDNA ends (RACE) PCR and
      haemocyte cDNA library screening. The full-length cDNA consists of 1734bp,
      encoding 411 amino acids with a calculated molecular mass of 46.55kDa and a
      theoretical isoelectric point of 7.70. Fc-serpin contains a typical serpin-like
      homologue (serine proteinase inhibitors domain). The deduced protein contains a
      putative signal peptide of 19 amino acids and the serpin's signature sequence
      ((379)FHCNRPFLFLI(389)). Fc-serpin showed some identity with Pacifastacus
      leniusculus serpin (42%) and Manduca sexta serpin-6 (34%). The reactive centre
      loop (RCL) sequences of Fc-serpin, P. leniusculus serpin, M. sexta serpin-6 and
      Bombyx mori serpin-2 are highly similar. An Arg at the P1 position of the
      reactive site indicates that Fc-serpin may have inhibitory activity against
      prophenoloxidase activating proteinase (PAP) and clotting enzyme. Transcripts of
      Fc-serpin mRNA were mainly detected in haemocytes and the lymphoid organ by RT
      PCR. The variation of the mRNA transcription level in haemocytes followed by
      artificial infection with bacteria or white spot syndrome virus (WSSV) was
      quantified by SYBR Green real-time PCR analysis. Expression profiles of Fc-serpin
      greatly fluctuated after challenge. This work represents the first report of a
      serpin in penaeid shrimp. The data provide clues that Fc-serpin might play
      potential roles in the innate immunity of shrimp.

PMID- 18817878
TI  - Chinese herbs (Astragalus radix and Ganoderma lucidum) enhance immune response of
      carp, Cyprinus carpio, and protection against Aeromonas hydrophila.
AB  - The effect of Chinese herbs (Astragalus radix and Ganoderma lucidum) on immune
      response of carp was investigated. Fish were fed diets containing Astragalus
      (0.5%), Ganoderma (0.5%) and combination of two herbs (Astragalus 0.5% and
      Ganoderma 0.5%) for 5 weeks. Other groups of fish were vaccinated (i.p.) against
      Aeromonas hydrophila/Aeromonas salmonicida (Shering Plough, Essex, U.K.) at the
      beginning of the experiment and fed the same diets as described above. Control
      fish (negative control) and fish vaccinated only (positive control) were fed
      basal diets without supplements of herbs. The respiratory burst activity,
      phagocytosis, lysozyme activity and circulatory antibody titres in plasma were
      monitored. Following 5 weeks after feeding, fish were infected with A. hydrophila
      and mortalities were recorded. The results of this study showed that feeding non
      vaccinated and vaccinated carp with combination of Astragalus and Ganoderma
      stimulated respiratory burst activity, phagocytosis of phagocytic cells in blood
      and lysozyme and circulatory antibody titres in plasma in vaccinated carp. Fish
      challenged with A. hydrophila had variable survival. The best survival (60%) was
      in vaccinated group fed with both herbs, while almost 90% of control fish
      (negative control) and 60% of fish vaccinated only (positive control) died.

PMID- 18817879
TI  - Classical crosses of common carp (Cyprinus carpio L.) show co-segregation of
      antibody response with major histocompatibility class II B genes.
AB  - In cyprinids, two paralogous groups of major histocompatibility (MH) class II B
      genes, DAB1 and DAB3, have been reported but have not been studied in detail. In
      our study on MH association with immune responsiveness in common carp (Cyprinus
      carpio L.) we have taken a long-term approach using divergent selection for
      antibody production. We report the co-segregation of Cyca-DAB1-like and Cyca-DAB3
      like genes with antibody response, in backcrosses to high- and low-responsive
      parental carp lines. We show that the presence of Cyca-DAB1-like, but not Cyca
      DAB3-like genes, preferentially leads to a high DNP-specific antibody response in
      carp. Background genes other than Cyca-DAB genes also influenced the level of
      antibody response. Our data support the hypothesis of a genetic control by Cyca
      DAB genes on the antibody response measured. We could not detect an association
      of the Cyca-DAB genes with disease resistance to the parasite Trypanoplasma
      borreli. Sequence information, constitutive transcription levels and our co
      segregation data indicate that both paralogous Cyca-DAB1-like and Cyca-DAB3-like
      groups represent functional MH class II B genes. Previously defined differences
      in allelic diversity between Cyca-DAB1-like genes, especially, identify Cyca-DAB1
      as the most interesting DAB gene for further study in common carp.

PMID- 18817880
TI  - A highly phagocytic cell line TO from Atlantic salmon is CD83 positive and M-CSFR
      negative, indicating a dendritic-like cell type.
AB  - Leucocyte cell lines are valuable tools for immunological studies. In this study
      the TO cell line, originating from Atlantic salmon head kidney leucocytes, is
      described with respect to enzyme cytochemistry, functional studies, reactivity
      with leucocyte specific antibodies and immune gene expression. Pronounced
      characteristics of the TO cell line are the rapid adherence to the plastic growth
      surface, high phagocytic capacity and bactericidal functions. No respiratory
      burst activity, and little or no NO production were detected under the
      experimental conditions tested, and thus the TO cells appear to have other
      effective killing mechanisms. The cells are reactive with a leucocyte specific
      monoclonal antibody (MAb), but does not bind a neutrophil specific MAb or stain
      for myeloperoxidase. Real-time RT-PCR showed the expression in TO cells of
      several immune genes, some of which were significantly regulated following LPS
      stimulation. The expression of CD83 might indicate a dendritic cell (DC) origin
      of the TO cells, as this marker is considered a hallmark for DC. Expression of
      TCR-alpha or the macrophage marker M-CSFR was not detected. Based on the present
      analyses the TO cells display a mixture of known characteristics for macrophages
      and DCs. At the same time the TO cells lack some central functions of
      phagocytic/myeloid cells. As the TO cells are developed to a long-term culture
      one cannot exclude that some functions might have been lost in this process.
      Nevertheless, the features of the TO cells indicate their potential as a model
      system for immunological studies of salmon phagocytic cells.

PMID- 18817881
TI  - Comparison of the biochemical composition of normal epidermal mucus and extruded
      slime of hagfish (Myxine glutinosa L.).
AB  - Hagfish (Myxine glutinosa) secrete normal epidermal mucus and extruded slime. The
      epidermal mucus is produced continuously to prevent pathogen adherence while the
      extruded slime is observed predominantly during feeding, provocation or stress.
      To date little is known about the involvement of extruded slime in the
      physiological functions of hagfish. In this preliminary study, innate immune
      enzymes and the protein composition of hagfish normal epidermal mucus and
      extruded slime were analysed and compared. The lysozyme specific activity of
      hagfish was observed approximately two-fold higher in extruded slime than that of
      epidermal mucus. The extruded slime had approximately 3.5-5.0 fold increased
      levels of alkaline phosphatase, cathepsin B and proteases in comparison to
      epidermal mucus. Protease characterization using specific inhibitors showed that
      the extruded slime had higher levels of serine trypsin-like proteases compared to
      metalloproteases whereas epidermal mucus showed equal proportion of both serine
      and metalloproteases. SDS-PAGE analysis showed high levels of three proteins with
      molecular masses in the range of 13-16kDa in the extruded slime. The LC/MS/MS
      analysis of protein bands 1, 2 and 3 showed closest matches to hemoglobulin-3,
      histone H3 and H2B proteins, respectively. The observation of elevated levels of
      innate immune parameters in the extruded slime suggested that the extruded slime
      has a significant role in innate immunity of hagfish against infectious
      pathogens.

PMID- 18817882
TI  - Test-retest reliability of EEG spectra during a working memory task.
AB  - The inter-individual variation of EEG spectra is large even for the same
      cognitive task. We asked whether task-induced EEG spectra remain stable over more
      than a year. We recorded EEG in 41 healthy adults who performed a modified
      Sternberg task. In 20 subjects EEG was recorded in a second session with retest
      intervals 12-40 months. For electrodes AFz, Cz and Pz peak frequency and peak
      height were determined. We compared the curve shape of power spectra by
      regressing spectra pairwise onto each other and calculated a t-value. The t-value
      and pairwise differences in peak frequency and peak height between all sessions
      were entered into a generalized linear model (GLM) where binary output represents
      the recognition probability. The results were cross-validated by out-of-sample
      testing. Of the 40 sessions, 35 were correctly matched. The shape of power
      spectra contributed most to recognition. Out of all 2400 pairwise comparisons
      99.3% were correct, with sensitivity 87.5% and specificity 99.5%. The intra
      individual stability is high compared to the inter-individual variation. Thus,
      interleaved EEG-fMRI measurements are valid. Furthermore, longitudinal effects on
      cognitive EEG can be judged against the intra-individual variability in subjects.

PMID- 18817883
TI  - Lateralization of the parietal old/new effect: an event-related fMRI study
      comparing recognition memory for words and faces.
AB  - Although the parietal cortex is not conventionally thought of as a major
      component of the neural systems that mediate declarative memory, many fMRI
      studies of recognition memory have found that correctly identified old items
      produce greater activation than correctly rejected new items throughout parietal
      cortex. This effect is usually heavily lateralized to the left. However, the vast
      majority of previous studies have used verbal materials. Does the left
      lateralization of this effect result from the left hemisphere's role in language
      or does it suggest the possibility of a specialized role for the left hemisphere
      in recognition memory that applies across stimulus domains? To address this
      question, we directly compared recognition memory for words and faces in two
      event-related fMRI experiments with a total of 38 subjects. In the second
      experiment, we included a manipulation of recognition difficulty. Despite
      extensive material-specific lateralization in terms of the brain's overall
      response to stimuli revealed by a direct comparison of words and faces, the
      parietal old/new effect did not exhibit material-specific lateralization. Rather,
      the lateralization of the effect depended on the region of parietal cortex in
      question. In lateral parietal cortex, the effect was left-lateralized. In medial
      parietal cortex, the effect was bilateral. These findings indicate that the left
      lateralization of the parietal old/new effect is unrelated to the left
      hemisphere's role in language and raises the possibility of a specialized role
      for the left hemisphere in recognition memory.

PMID- 18817884
TI  - The oldest fossil evidence of animal parasitism by fungi supports a Cretaceous
      diversification of fungal-arthropod symbioses.
AB  - Paleoophiocordyceps coccophagus, a fungal parasite of a scale insect from the
      Early Cretaceous (Upper Albian), is reported and described here. This fossil not
      only provides the oldest fossil evidence of animal parasitism by fungi but also
      contains morphological features similar to asexual states of Hirsutella and
      Hymenostilbe of the extant genus Ophiocordyceps (Ophiocordycipitaceae,
      Hypocreales, Sordariomycetes, Pezizomycotina, Ascomycota). Because species of
      Hypocreales collectively exhibit a broad range of nutritional modes and symbioses
      involving plants, animals and other fungi, we conducted ancestral host
      reconstruction coupled with phylogenetic dating analyses calibrated with
      P.coccophagus. These results support a plant-based ancestral nutritional mode for
      Hypocreales, which then diversified ecologically through a dynamic process of
      intra- and interkingdom host shifts involving fungal, higher plant and animal
      hosts. This is especially evident in the families Cordycipitaceae,
      Clavicipitaceae and Ophiocordycipitaceae, which are characterized by a high
      occurrence of insect pathogens. The ancestral ecologies of Clavicipitaceae and
      Ophiocordycipitaceae are inferred to be animal pathogens, a trait inherited from
      a common ancestor, whereas the ancestral host affiliation of Cordycipitaceae was
      not resolved. Phylogenetic dating supports both a Jurassic origin of fungal
      animal symbioses within Hypocreales and parallel diversification of all three
      insect pathogenic families during the Cretaceous, concurrent with the
      diversification of insects and angiosperms.

PMID- 18817885
TI  - Correctly assigning original discoveries to original authors.

PMID- 18817886
TI  - Go no-go performance under psychosocial stress: beneficial effects of
      implementation intentions.
AB  - Acute stress has been found to have negative and implementation intentions (IIs)
      to have positive effects on cognitive performance. This study was the first to
      examine the effects of IIs on executive action control under acute psychosocial
      stress. Forty-two male subjects aged 21-39 years were randomly assigned to the
      Trier Social Stress Test (TSST) versus a rest condition. In addition, the
      instruction to the executive task (a go no-go task) was manipulated (IIs versus
      standard instruction). After the stress test, a dual-task procedure including a
      go no-go task was conducted. The TSST resulted in increases in cortisol response,
      heart rate and state anxiety compared to the rest condition. Acute stress
      significantly impaired go no-go performance, but only in the group without IIs.
      We conclude that under acute stress conditions executive functioning is reduced,
      but the use of IIs can be an effective strategy to overcome this negative effect.

PMID- 18817887
TI  - Photic and circadian regulation of melatonin production in the Mozambique tilapia
      Oreochromis mossambicus.
AB  - Diverse circadian systems related to phylogeny and ecological adaptive strategies
      are proposed in teleosts. Recently, retinal photoreception was reported to be
      important for the circadian pacemaking activities of the Nile tilapia Oreochromis
      niloticus. We aimed to confirm the photic and circadian responsiveness of its
      close relative-the Mozambique tilapia O. mossambicus. Melatonin production in
      cannulated or ophthalmectomized fish and its secretion from cultured pineal
      glands were examined under several light regimes. Melatonin production in the
      cannulated tilapias was measured at 3-h intervals; it fluctuated daily, with a
      nocturnal increase and a diurnal decrease. Exposing the cannulated fish to
      several light intensities (1500-0.1 lx) and to natural light (0.1 and 0.3 lx)
      suppressed melatonin levels within 30 min. Static pineal gland culture under
      light-dark and reverse light-dark cycles revealed that melatonin synthesis
      increased during the dark periods. Rhythmic melatonin synthesis disappeared on
      pineal gland culture under constant dark and light conditions. After
      ophthalmectomy, plasma melatonin levels did not vary with light-dark cycles.
      These results suggest that (1) Mozambique tilapias possess strong photic
      responsiveness, (2) their pineal glands are sensitive to light but lack circadian
      pacemaker activity, and (3) they require lateral eyes for rhythmic melatonin
      secretion from the pineal gland.

PMID- 18817888
TI  - Guinea pig model of Mycobacterium tuberculosis latent/dormant infection.
AB  - Although guinea pigs are considered one of the best animal models of
      tuberculosis, little data exist describing latent or dormant tuberculosis
      infection in these animals. Here we address this issue using a streptomycin
      auxotrophic mutant of Mycobacterium tuberculosis. This mutant grows unimpaired in
      the presence of streptomycin but in its absence shifts to latency/dormancy (lack
      growth and over-expression of alpha-crystallin). To establish infection animals
      are inoculated with the mutant followed by daily administration of streptomycin
      (three weeks), which allows initial microbial multiplication in the animal's
      tissues. Withdrawal of streptomycin establishes latency/dormancy and few viable
      organisms are recovered from the animals' lungs and spleen six months later.
      During the infectious process guinea pigs steadily gained weight and presented no
      clinical signs (scuff fur and lethargy) of disease. Histopathology of organs
      mimicked tuberculous lesions in humans and PBMC from infected animals strongly
      responded to stimulation with PPD. Finally, tuberculin skin test (a hallmark of
      latent infection diagnosis) performed in infected animals was strongly positive
      (>or=15 mm induration). These results point to an interesting and reliable model
      of latent/dormant tuberculosis infection in guinea pigs.

PMID- 18817889
TI  - Transpeptidation and reverse proteolysis and their consequences for immunity.
AB  - Reverse proteolysis and transpeptidation lead to the generation of polypeptide
      sequences that cannot be inferred directly from genome sequences as they are post
      translational phenomena. These phenomena have so far received little attention
      although the physiological consequences may reach far. The protease-mediated
      synthesis of several immunodominant MHC class I antigens was recently reported,
      underscoring its importance to immunity. Reverse proteolytic and transpeptidation
      mechanisms as well as conditions that favor successful protease-catalyzed
      synthetic events are discussed here.

PMID- 18817890
TI  - Chromatin remodeling, metabolism and circadian clocks: the interplay of CLOCK and
      SIRT1.
AB  - Circadian rhythms govern a wide variety of physiological and metabolic functions
      in almost all organisms. These are controlled by the circadian clock machinery,
      which is mostly based on transcriptional-translational feedback loops.
      Importantly, 10-15% of the mammalian transcripts oscillate in a circadian manner.
      The complex program of gene expression that characterizes circadian physiology is
      possible through dynamic changes in chromatin transitions. These remodeling
      events are therefore of great importance to insure the proper timing and extent
      of circadian regulation. Recent advances in the field have revealed unexpected
      links between circadian regulators, chromatin remodeling and cellular metabolism.
      Specifically, the central clock protein CLOCK has HAT enzymatic properties. It
      directs acetylation of histone H3 and of its dimerization partner BMAL1 at K537,
      an event essential for circadian function. In addition, the HDAC activity of the
      NAD(+)-dependent SIRT1 enzyme is regulated in a circadian manner. It has been
      proposed that SIRT1 functions as an enzymatic rheostat of circadian function,
      transducing signals originated by cellular metabolites to the circadian clock.
      Thus, a specialized program of chromatin remodeling appears to be at the core of
      the circadian machinery.

PMID- 18817891
TI  - A renaissance for the pioneering 16S rRNA gene.
AB  - Culture-independent molecular surveys using the 16S rRNA gene have become a
      mainstay for characterizing microbial community structure over the past quarter
      century. More recently this approach has been overshadowed by metagenomics, which
      provides a global overview of a community's functional potential rather than just
      an inventory of its inhabitants. However, the pioneering 16S rRNA gene is making
      a comeback in its own right thanks to a number of methodological advancements
      including higher resolution (more sequences), analysis of multiple related
      samples (e.g. spatial and temporal series) and improved metadata, and use of
      metadata. The standard conclusion that microbial ecosystems are remarkably
      complex and diverse is now being replaced by detailed insights into microbial
      ecology and evolution based only on this one historically important marker gene.

PMID- 18817892
TI  - Glucocorticoid receptor-mediated upregulation of human CYP27A1, a potential anti
      atherogenic enzyme.
AB  - Sterol 27-hydroxylase (CYP27A1) is required for the hepatic conversion of
      cholesterol into bile acids and for production of 27-hydroxycholesterol which
      affects cholesterol homeostasis in several ways. Dexamethasone increases hepatic
      bile acid biosynthesis and CYP27A1-mediated enzyme activity in HepG2 cells. This
      study examines the mechanism of the dexamethasone-induced effect on the human
      CYP27A1 promoter. Dexamethasone treatment of HepG2 cells overexpressed with
      glucocorticoid receptor alpha (GRalpha) increased the CYP27A1 promoter activity
      more than four-fold as compared with untreated cells. The GR-antagonist
      mifepristone almost completely abolished the dexamethasone-induced effect on the
      promoter activity. Progressive deletion analysis of the CYP27A1 promoter
      indicated that sequences involved in GR-mediated induction by dexamethasone are
      present in a region between -1094 and -792. Several putative GRE sites could be
      found in this region and EMSA experiments revealed that two of these could bind
      GR. Site-directed mutagenesis of GR-binding sequences in the CYP27A1 promoter
      identified a GRE at -824/-819 important for GR-mediated regulation of the
      transcriptional activity. Endogenous and pharmacological glucocorticoids may have
      a strong impact on several aspects of cholesterol homeostasis and other processes
      related to CYP27A1-mediated metabolism. The glucocorticoid-mediated induction of
      human CYP27A1 transcription is of particular interest due to the anti-atherogenic
      properties ascribed to this enzyme.

PMID- 18817893
TI  - Expression patterns of cadherin genes in Drosophila oogenesis.
AB  - In Drosophila oogenesis, the follicular epithelium that envelops the oocyte is
      patterned by a small set of inductive signals and gives rise to an elaborate
      three-dimensional eggshell. Several eggshell structures provide sensitive
      readouts of the patterning signals, but the formation of these structures is
      still poorly understood. In other systems, epithelial morphogenesis is guided by
      the spatial patterning of cell adhesion and cytoskeleton genes. As a step towards
      developing a comprehensive description of patterning events leading to eggshell
      morphogenesis, we report the expression of Drosophila cadherins, calcium
      dependent adhesion molecules that are repeatedly used throughout development. We
      found that 9/17 of Drosophila cadherins are expressed in the follicular
      epithelium in dynamic patterns during oogenesis. In late oogenesis, the
      expression patterns of cadherin genes in the main body follicle cells is
      summarized using a compact set of simple geometric shapes, reflecting the
      integration of the EGFR and DPP inductive signals. The multi-layered composite
      patterning of the cadherins is hypothesized to play a key role in the formation
      of the eggshell. Of particular note is the complex patterning of the region of
      the follicular epithelium that gives rise to the dorsal appendages, which are
      tubular structures that serve as respiratory organs for the developing embryo.

PMID- 18817894
TI  - Effects of a new nutraceutical ingredient on allergen-induced
      sulphidoleukotrienes production and CD63 expression in allergic subjects.
AB  - Allergic diseases represent conditions affecting millions of individuals across
      the world. The objective of this study was to investigate the potential anti
      allergic effects of a new nutraceutical ingredient, Pantescal (Bionap, Italy),
      contained in different food supplements. Pantescal is a mixture of plant
      extracts, such as Capparis spinosa, Olea europaea, Panax Ginseng and Ribes
      nigrum. The study was a randomized, double-blind, placebo controlled design. 60
      patients allergic to common aeroallergens were chosen. Allergic patients were
      divided into two groups: one group was supplemented by Pantescal and the other,
      using a placebo formulation. Two in vitro tests were performed on blood samples
      taken from patients before and at 2 h, 2, 3 and 10 days after supplementation:
      cellular antigen stimulation test (CAST) was used to analyze the amount of
      sulphidoleukotrienes (SLT) production and flow-cytometric antigen stimulation
      test (FAST) to measure expression of basophil degranulation marker (CD63) was
      also performed. CAST showed that after 2 and 3 days, a slight decrease of SLT
      production was evident but only after 10 days did it become significant with a
      percentage of inhibition (P.I)=43.3%. FAST revealed that there were no
      statistical differences for the first 2 days after supplementation although there
      was an inhibitory trend in the supplemented patients. CD63 expression was
      significantly reduced after 10 days (P.I.=64.8%). This study suggests that
      Pantescal is effective in reducing allergic biomarkers such as CD63 protein and
      SLT in atopic subjects. The higher inhibitory effect on CD63 expression compared
      to SLT production allows us to hypothesize cell membrane stabilization as the
      main potential mechanism to explain the observed Pantescal protective effects.

PMID- 18817895
TI  - An anti-transferrin receptor antibody enhanced the growth inhibitory effects of
      chemotherapeutic drugs on human non-hematopoietic tumor cells.
AB  - Transferrin receptor (TfR) has been used as a target for antibody-based therapy
      of cancer. Combining anti-TfR antibodies with chemotherapeutic drugs shows
      potential as one of the strategies for cancer therapy. In this study, we
      investigated the effects of anti-TfR monoclonal antibody 7579 alone or in
      combination with chemotherapeutic drugs (5-fluorouracil or doxorubicin) on non
      hematopoietic tumor cells (HepG2 and MCF-7) in vitro. We found that 7579 mAb
      alone could dramatically down-regulate surface TfR expression on tumor cells.
      Consequently, marked S phase arrest and apoptosis were observed in 7579 mAb
      treated tumor cells. In combination with 5-fluorouracil or doxorubicin, 7579 mAb
      enhanced the growth inhibitory effects of chemotherapeutic drugs on tumor cells.
      Results of 7AAD/Annexin V staining demonstrated that 7579 mAb enhanced the
      cytotoxic effects of chemotherapeutic drugs on tumor cells by mainly promoting
      tumor cell necrosis. Using the median-effect/combination-index isobologram
      method, we further evaluated the nature of 7579 mAb/chemotherapeutic drug
      interactions. Synergistic interaction was observed for 7579 mAb combined with 5
      fluorouracil whereas additive efficacy was observed for 7579 mAb plus
      doxorubicin. Our study provided the basis to further develop 7579 mAb-containing
      chemoimmunotherapy for non-hematopoietic malignancies.

PMID- 18817896
TI  - Detrimental effects of hyperandrogenism on uterine functions.
AB  - The aim of the present work was to study some of the adverse effects produced by
      hyperandrogenism on the uterine function. Daily injection of
      dehydroepiandrosterone (DHEA: 6 mg/ 100 g body weight, sc) for 20 consecutive
      days induced polycystic ovaries in BALB/c mice. In this model, we found that DHEA
      produced alterations on uterine histology closely related to the development of
      tumour structures. In addition, hyperandrogenism induced a pro-inflammatory and a
      pro-oxidant condition represented by increased levels of prostaglandin F2 alpha
      production and uterine nitric oxide synthase (NOS) activity and by a decrease in
      both superoxide dismutase (SOD) and catalase (CAT) activities together with a
      decrease in the levels of the antioxidant metabolite glutathione (GSH). DHEA also
      induced an increase in CD4+ together with a decrease in the CD8+ T lymphocytes
      that infiltrate the uterine tissue. We conclude that this intricate network of
      regulators could be responsible for the low rate of implantation observed in
      women with polycystic ovary syndrome.

PMID- 18817897
TI  - Comparative study of nucleotide excision repair defects between XPD-mutated
      fibroblasts derived from trichothiodystrophy and xeroderma pigmentosum patients.
AB  - To get a clue to understand how mutations in the XPD gene result in different
      skin cancer susceptibilities in patients with xeroderma pigmentosum (XP) or
      trichothiodystrophy (TTD), a thorough understanding of their nucleotide excision
      repair (NER) defects is essential. Here, we extensively characterize the possible
      causes of NER defects in XP-D and in TTD fibroblasts. The 3 XP-D cell strains
      examined were similarly deficient in repairing UV-induced cyclobutane pyrimidine
      dimers (CPDs) and (6-4) photoproducts (6-4PPs) from genomic DNA. The severity of
      NER defects correlated with their UV sensitivities. Possible alterations of TFIIH
      (which consists of 10 subunits including XPD) were then examined. All XP-D cell
      strains were normal in their concentrations of TFIIH, and displayed normal
      abilities to recruit TFIIH to sites of UV-induced DNA damage. However,
      replication protein A (RPA; single-stranded DNA binding protein) accumulation at
      DNA damage sites, which probably reflects the in vivo XPD helicase activity of
      TFIIH, is similarly impaired in all XP-D cell strains. Meanwhile, all 3 TTD cell
      strains had approximately 50% decreases in cellular TFIIH content. Importantly, 2
      of the 3 TTD cell strains, which carry the major XPD mutations found in TTD
      patients, showed defective recruitment of TFIIH to DNA damage sites. Moreover,
      RPA accumulation at damage sites was impaired in all TTD cell strains to
      different degrees, which correlated with the severity of their NER defects. These
      results demonstrate that XP-D and TTD cells are both deficient in the repair of
      CPDs and 6-4PPs, but TTD cells have more multiple causes for their NER defects
      than do XP-D cells. Since TFIIH is a repair/transcription factor, TTD-specific
      alterations of TFIIH possibly result in transcriptional defects, which might be
      implication for the lack of increased incidence of skin cancers in TTD patients.

PMID- 18817898
TI  - Yeast Elc1 plays an important role in global genomic repair but not in
      transcription coupled repair.
AB  - Transcription coupled repair (TCR) is a nucleotide excision repair (NER) pathway
      that is dedicated to repair in the transcribed strand of an active gene. The
      genome overall NER is called global genomic repair (GGR). Elc1, the yeast homolog
      of the mammalian elongation factor elongin C, has been shown to be a component of
      a ubiquitin ligase complex that contains Rad7 and Rad16, two factors that are
      specifically required for GGR. Elc1 has also been suggested to be present in
      another ubiquitin ligase complex that lacks Rad7 and Rad16 and is involved in UV
      induced ubiquitylation and subsequent degradation of RNA polymerase II. Here we
      show that elc1 deletion increases UV sensitivity of TCR-deficient cells but does
      not affect the UV sensitivity of otherwise wild type and GGR-deficient cells.
      Cells deleted for elc1 show normal NER in the transcribed strand of an active
      gene but have no detectable NER in the non-transcribed strand. Elc1 does not
      affect UV-induced mutagenesis when TCR is operative, but plays an important role
      in preventing the mutagenesis if TCR is defective. Furthermore, the levels of
      Rad7 and Rad16 proteins are not significantly decreased in elc1 cells, and
      overexpression of Rad7 and Rad16 individually or simultaneously in elc1 cells
      does not restore repair in the non-transcribed strand of an active gene. Our
      results suggest that Elc1 has no function in TCR but plays an important role in
      GGR. Furthermore, the role of Elc1 in GGR may not be subsidiary to that of Rad7
      and Rad16.

PMID- 18817899
TI  - Cardiovascular involvement in systemic autoimmune diseases.
AB  - Autoimmune diseases, including rheumatoid arthritis (RA), systemic lupus
      erythematosus (SLE), primary antiphospholipid syndrome (APS), systemic sclerosis
      and systemic vasculitis, affect a large number of people in whom one of the
      leading causes of morbidity and mortality is cardiovascular disease.
      Cardiovascular disease is associated with the development of accelerated
      atherosclerosis. It seems to occur at a younger age than in the general
      population, is often asymptomatic and, in addition to traditional risk factors,
      also involves specific risk factors as chronic inflammation, the duration and
      activity of the autoimmune disease, and immunosuppressive therapy. The early
      phases of cardiovascular involvement in patients with autoimmune diseases may be
      clinically silent, with only a microcirculation disorder present. There are
      various means of detecting morphological cardiac damage: coronary angiography
      remains the gold standard for diagnosing coronary stenosis, but new, non invasive
      and more reliable methods have been introduced into clinical practice in order to
      detect subclinical microcirculation abnormalities.

PMID- 18817900
TI  - Protein complexes in bacterial and yeast mitochondrial membranes differ in their
      sensitivity towards dissociation by SDS.
AB  - Previously, a 2D gel electrophoresis approach was developed for the Escherichia
      coli inner membrane, which detects membrane protein complexes that are stable in
      sodium dodecyl sulfate (SDS) at room temperature, and dissociate under the
      influence of trifluoroethanol [R. E. Spelbrink et al., J. Biol. Chem. 280 (2005),
      28742-8]. Here, the method was applied to the evolutionarily related
      mitochondrial inner membrane that was isolated from the yeast Saccharomyces
      cerevisiae. Surprisingly, only very few proteins were found to be dissociated by
      trifluoroethanol of which Lpd1p, a component of multiple protein complexes
      localized in the mitochondrial matrix, is the most prominent. Usage of either
      milder or more stringent conditions did not yield any additional proteins that
      were released by fluorinated alcohols. This strongly suggests that membrane
      protein complexes in yeast are less stable in SDS solution than their E. coli
      counterparts, which might be due to the overall reduced hydrophobicity of
      mitochondrial transmembrane proteins.

PMID- 18817901
TI  - Lifetime absolute risk of hip and other osteoporotic fracture in Belgian women.
AB  - OBJECTIVES: To estimate the lifetime absolute risks of hip and other osteoporotic
      fracture in Belgian women aged 60 years and to examine the effect of changes in
      baseline population fracture risk and changes in life expectancy. MATERIALS AND
      METHODS: Estimates were performed using a Markov microsimulation model and were
      based on the incidence of first fracture as well as life expectancy. Baseline
      scenario included projected mortality rates and increasing fracture incidence by
      1% per year. Alternative scenarios were performed on age, life expectancy and
      trends in fracture incidence. Lifetime fracture risk for osteoporotic population
      (T-score <or= -2.5) was also estimated. RESULTS: In the baseline scenario,
      lifetime absolute risks of hip fracture and of any major osteoporotic fracture
      (hip, clinical vertebral or wrist) were respectively 24.8% and 44.3%. Alternative
      scenarios showed that when assuming no change of age-specific fracture rates over
      time, these lifetime risks were 18.3% and 35.2%, while these values were 20.0%
      and 38.3% assuming no future mortality reductions. For osteoporotic women, these
      values were respectively 34.5% and 51.5%. CONCLUSION: We conclude that absolute
      lifetime fracture risks are substantial and that trends in fracture incidence and
      changes in life expectancy have a marked impact on absolute lifetime fracture
      risks.

PMID- 18817902
TI  - Sex steroids and bone turnover markers in men with symptomatic vertebral
      fractures.
AB  - Sex steroids play an important role in the maintenance of bone density in men and
      women, but the circulating, biologically active unbound fraction is influenced by
      the concentration of sex hormone binding globulin (SHBG). SHBG increases with
      advancing age in men and leads to a reduction in serum free testosterone and
      oestradiol, which may then affect bone turnover, bone mineral density (BMD) and
      the risk of fractures. We have therefore measured total and unbound sex steroids,
      SHBG, bone turnover markers and BMD in 57 men with symptomatic low trauma
      vertebral fractures and 57 age-matched male control subjects. Fasting blood and
      urine samples were collected from all subjects, who also underwent BMD
      measurement of the lumbar spine and hip. Serum testosterone, oestradiol, SHBG,
      bone specific alkaline phosphatase (bone ALP) and urine free
      deoxypyridinoline/creatinine ratio (fDPD/Cr) were measured. Free sex steroid
      concentrations were calculated using their ratio with SHBG and albumin and
      bioavailable testosterone was measured using radioimmunoassay. The two groups
      were then compared and regression models developed to determine the best
      predictors of BMD and fracture. Men with vertebral fractures had significantly
      lower weight and BMD at all sites than control subjects (p<0.0001). Serum total
      testosterone and oestradiol did not differ between the two groups, but calculated
      free androgen and free oestradiol indices were lower in the fracture group than
      the control subjects (p=0.04), due to higher SHBG (46.6 versus 36.1 nmol/L:
      p=0.005). The men with vertebral fractures had significantly higher mean bone ALP
      (15.8 versus 11.8 microg/L: p=0.002) and fDPD/Cr (5.5 versus 4.0 nmol/mmol:
      p=0.03). Stepwise multiple regression analysis in both fracture and control
      groups found body weight to be the best predictor of BMD. In the fracture group
      weight predicted between 19.7 and 30.7% of the variance in BMD and in control
      subjects this was between 12.3 and 13.2%. SHBG contributed to the model for hip
      BMD in the fracture group alone, so that weight and SHBG together accounted for
      32 to 42.9% of the variance. A model combining BMD at the spine, total femur and
      femoral neck with height loss best predicted fracture. In conclusion, men with
      symptomatic vertebral fractures have higher SHBG and lower calculated free sex
      steroid indices, increased bone turnover and lower BMD. Whilst body weight was
      the best predictor of BMD, symptomatic vertebral fracture was best predicted by
      BMD and height loss.

PMID- 18817903
TI  - Mutations in LPIN1 cause recurrent acute myoglobinuria in childhood.
AB  - Recurrent episodes of life-threatening myoglobinuria in childhood are caused by
      inborn errors of glycogenolysis, mitochondrial fatty acid beta-oxidation, and
      oxidative phosphorylation. Nonetheless, approximately half of the patients do not
      suffer from a defect in any of these pathways. Using homozygosity mapping, we
      identified six deleterious mutations in the LPIN1 gene in patients who presented
      at 2-7 years of age with recurrent, massive rhabdomyolysis. The LPIN1 gene
      encodes the muscle-specific phosphatidic acid phosphatase, a key enzyme in
      triglyceride and membrane phospholipid biosynthesis. Of six individuals who
      developed statin-induced myopathy, one was a carrier for Glu769Gly, a pathogenic
      mutation in the LPIN1 gene. Analysis of phospholipid content disclosed
      accumulation of phosphatidic acid and lysophospholipids in muscle tissue of the
      more severe genotype. Mutations in the LPIN1 gene cause recurrent rhabdomyolysis
      in childhood, and a carrier state may predispose for statin-induced myopathy.

PMID- 18817904
TI  - Japanese population structure, based on SNP genotypes from 7003 individuals
      compared to other ethnic groups: effects on population-based association studies.
AB  - Because population stratification can cause spurious associations in case-control
      studies, understanding the population structure is important. Here, we examined
      Japanese population structure by "Eigenanalysis," using the genotypes for 140,387
      SNPs in 7003 Japanese individuals, along with 60 European, 60 African, and 90
      East-Asian individuals, in the HapMap project. Most Japanese individuals fell
      into two main clusters, Hondo and Ryukyu; the Hondo cluster includes most of the
      individuals from the main islands in Japan, and the Ryukyu cluster includes most
      of the individuals from Okinawa. The SNPs with the greatest frequency differences
      between the Hondo and Ryukyu clusters were found in the HLA region in chromosome
      6. The nonsynonymous SNPs with the greatest frequency differences between the
      Hondo and Ryukyu clusters were the Val/Ala polymorphism (rs3827760) in the EDAR
      gene, associated with hair thickness, and the Gly/Ala polymorphism (rs17822931)
      in the ABCC11 gene, associated with ear-wax type. Genetic differentiation was
      observed, even among different regions in Honshu Island, the largest island of
      Japan. Simulation studies showed that the inclusion of different proportions of
      individuals from different regions of Japan in case and control groups can lead
      to an inflated rate of false-positive results when the sample sizes are large.

PMID- 18817905
TI  - [How to interpret CT-scan in presence of conductive hearing loss or mixed hearing
      loss with normal tympanic membrane?].

PMID- 18817906
TI  - Higher levels of salivary MUC5B and MUC7 in individuals with gastric diseases who
      harbor Helicobacter pylori.
AB  - OBJECTIVE: The aim of the present study was to assess the salivary levels of
      MUC5B and MUC7 in individuals with dyspeptic disease and Helicobacter pylori (H.
      pylori) in the stomach, compared to individuals without dyspeptic disease.
      METHODS: 30 individuals with dyspeptic disease, who underwent endoscopy for upper
      gastrointestinal complaints at Hospital Pedro Ernesto-RJ, Brasil and tested
      positive for H. pylori, and 23 controls with no dyspeptic disease, with mean age
      53.5+/-4.4 years, were included in the study. Saliva samples and 3 antral biopsy
      were taken for PCR analysis and histologic examination. In addition, saliva
      samples were tested by ELISA with F2 monoclonal antibody and EU7A antibody
      against MUC7, to determine MUC5B and MUC7 levels, prior to endoscopic
      examination. The expression pattern of the proteins was quantified by comparison
      to a pooled saliva sample of 19 healthy volunteers. RESULTS: MUC5B and MUC7
      salivary levels were higher in the individuals with dyspeptic disease than in
      controls (p<0.0001). 33.3% (9/30) of the dyspeptic individuals and 0% of the
      controls had H. pylori in the oral cavity. CONCLUSIONS: Individuals with gastric
      diseases, with H. pylori in the stomach, showed higher levels of salivary H.
      pylori receptors-MUC5B and MUC7-than individuals without gastric diseases. These
      results suggest that higher levels of specific salivary mucins could be useful as
      risk indicators for infection by H. pylori.

PMID- 18817907
TI  - Schizotypy and false memory.
AB  - Using the Deese-Roediger-McDermott (DRM) paradigm the present study examined the
      relationship between schizotypy and recognition memory. Participants scoring in
      the upper and lower quartile ranges for schizotypy (Schizotypal Personality
      Questionnaire brief version; SPQ-B) and on each of the SPQ-B subscales (cognitive
      perceptual, interpersonal and disorganized) were compared on true and false
      memory performance. Participants scoring in the lower quartile range on the
      cognitive-perceptual subscale recognised a higher proportion of both true and
      false memories than those scoring in the higher quartile range. Participants
      scoring in the upper quartile on the interpersonal factor recognised fewer true
      items than those in the lower quartile range. No differences were found for
      overall schizotypy or on the disorganized subscale.

PMID- 18817908
TI  - Commentary on the association of polychlorinated biphenyls with hypertension.

PMID- 18817909
TI  - Effectiveness, safety, and acceptability of cryotherapy by midwives for cervical
      intraepithelial neoplasia in Maharashtra, India.
AB  - OBJECTIVE: To evaluate the effectiveness, safety, and acceptability of
      cryotherapy for cervical intraepithelial neoplasia (CIN) when provided by trained
      midwives in rural India. METHOD: Women with colposcopic findings of CIN lesions
      suitable for ablative treatment received cryotherapy from trained midwives before
      the biopsy results were known. Cure rates, adverse effects, and complications
      were assessed and factors influencing cure rates were evaluated by chi(2) tests.
      Cure was defined as no clinical or histologic evidence of CIN lesions 6 or more
      months after treatment. RESULTS: Of 1068 women treated with cryotherapy, 728 had
      histologically proven CIN in their pretreatment biopsy specimens; of the 574
      reporting for follow-up, 538 (93.7%) were cured (95% confidence interval [CI],
      92.1%-96.3%). Cure rates were 96.4% (95% CI, 94.6%-98.1%) for CIN 1 and 82.1%
      (95% CI, 74.7%-89.4%) for CIN 2 and CIN 3 lesions combined. Minor adverse effects
      were documented in 5.2% of the women. CONCLUSION: Cryotherapy provided by
      midwives was found to be safe, effective, and acceptable by the women.

PMID- 18817911
TI  - Taxonomies of nursing diagnoses: a psychologist's view.

PMID- 18817912
TI  - Supramolecular solid-phase extraction of ibuprofen and naproxen from sewage based
      on the formation of mixed supramolecular aggregates prior to their liquid
      chromatographic/photometric determination.
AB  - Sorbents made up of sodium dodecyl sulphate (SDS) hemimicelles, formed onto gamma
      alumina, were proposed for the quantitative and practically solvent-free solid
      phase extraction (SPE) of ibuprofen and naproxen from sewage samples. The
      formation of drug-SDS mixed aggregates was proved by the pseudophase separation
      model and their composition as a function of the amount of drug was calculated.
      The overall hemimicellar SPE procedure consumed only 0.6 mL of methanol since non
      organic solvent was required for cartridge conditioning and the drugs were
      completely eluted using 2 mL of a 0.3M NaOH:methanol (70:30, v/v) solution.
      Breakthrough volumes of around 0.75 L and above 1L were obtained for naproxen and
      ibuprofen, respectively. No clean-up steps were necessary for the determination
      of these drugs in sewage because the direct analysis of the eluates by liquid
      chromatography/UV was matrix effect-free. The identification of the analytes was
      based on retention times and UV spectra and it was confirmed by on-line
      fluorescence detection. The detection limits for naproxen and ibuprofen were 0.8
      and 9 ng L(-1) in wastewater influents and 0.5 and 7 ng L(-1) in effluents,
      respectively. These limits were similar to or lower than those achieved by
      methods based on conventional sorbents (e.g. C(18)-silica or polymeric resins),
      which invariably require the evaporation of the eluates. The accuracy and
      precision of the proposed method were assessed by analysing influent and effluent
      wastewater samples spiked with 2 and 0.4 microg L(-1) of each analyte,
      respectively. The recoveries obtained and the corresponding standard deviations
      were in the ranges 93-101% and 2-9%. The method was applied to the determination
      of the target drugs in wastewater from three sewage treatment plants (STPs) in
      the south of Spain. The concentration of ibuprofen and naproxen ranged between
      2.0 and 7.4 microg L(-1) and 0.9 and 3.3 microg L(-1) in influents and 0.4 and
      1.4 microg L(-1) and 0.2 and 0.8 microg L(-1) in effluents, respectively.

PMID- 18817910
TI  - Prospective prenatal serum screening for Down syndrome in Venezuela.
AB  - OBJECTIVE: To assess the usefulness of triple-marker screening for Down syndrome
      in Venezuela. METHOD: Maternal serum concentrations of alpha fetoprotein (AFP),
      beta human chorionic gonadotropin (beta-hCG), and unconjugated estriol (uE3) were
      measured weekly in 3895 women from the 15th to the 20th week of pregnancy.
      Population-specific likelihood ratios were determined and used to calculate the
      risk of fetal Down syndrome for each pregnancy. RESULTS: The median multiple of
      the median values for AFP, beta-hCG, and uE3 concentrations were 0.69, 2.10, and
      0.67 for the affected pregnancies. The likelihood ratio for a positive result was
      1:19. The detection and false-positive rates were 69.23% and 5.8%. CONCLUSION:
      These findings were consistent with reported data and therefore confirmed triple
      marker serum screening as effective and suitable for prenatal care in Venezuela.
      Latin American governments and Health Agencies should recommend offering this
      screening method to all pregnant women.

PMID- 18817914
TI  - Trace analysis of per- and polyfluorinated alkyl substances in various matrices
      how do current methods perform?
AB  - Per- and polyfluorinated alkyl substances (PFAS) are a group of industrial
      chemicals, some of which have been produced for over 50 years. Scarcely one
      decade ago, their ubiquity in wildlife, humans and the global environment was
      discovered. This urged the need for robust and reliable, yet very sensitive
      analytical methods allowing for their determination in various matrices. This
      article reviews the state-of-the-art in trace analysis of ionic and neutral PFAS
      in humans as well as environmental samples such as wildlife, water, solid
      matrices and air. Analytical protocols for PFAS determination in food and
      consumer products are also included. The methods are critically discussed in
      terms of their advantages, shortcomings, possibilities, limitations, and
      potential for further development.

PMID- 18817913
TI  - Flavylium chromophores as species markers for dragon's blood resins from Dracaena
      and Daemonorops trees.
AB  - A simple and rapid liquid chromatographic method with diode-array UV-vis
      spectrophotometric detection has been developed for the authentication of
      dragon's blood resins from Dracaena and Daemonorops trees. Using this method it
      was discovered that the flavylium chromophores, which contribute to the red
      colour of these resins, differ among the species and could be used as markers to
      differentiate among species. A study of parameters, such as time of extraction,
      proportion of MeOH and pH, was undertaken to optimise the extraction of the
      flavyliums. This method was then used to make extracts from samples of dragon's
      blood resin obtained from material of known provenance. From the samples analysed
      7,6-dihydroxy-5-methoxyflavylium (dracorhodin), 7,4'-dihydroxy-5-methoxyflavylium
      (dracoflavylium) and 7,4'-dihydroxyflavylium were selected as species markers for
      Daemonorops spp., Dracaena draco and Dracaena cinnabari, respectively. The
      chromatograms from these samples were used to build an HPLC-DAD database. The
      ability to discriminate among species of dragon's blood using the single marker
      compounds was compared with a principal components analysis of the chromatograms
      in the HPLC-DAD database. The results from the HPLC-DAD method based on the
      presence of these flavylium markers was unequivocal. The HPLC-DAD method was
      subsequently applied to 37 samples of dragon blood resins from the historical
      samples in the Economic Botany Collection, Royal Botanic Gardens, Kew. The method
      identified anomalies in how samples in this collection had been labelled. It is
      clear that the method can be used to evaluate the provenance of samples used in
      different areas of cultural heritage. It also could be used to monitor the trade
      of endangered species of dragon's blood and the species being used in complex
      formulations of traditional Chinese medicine.

PMID- 18817915
TI  - Multi-residue contaminants and pollutants analysis in saffron spice by stir bar
      sorptive extraction and gas chromatography-ion trap tandem mass spectrometry.
AB  - A method for the simultaneous determination of 46 semi-volatile organic
      contaminants and pollutants in saffron has been developed for the first time
      using a stir bar sorptive extraction technique and thermal desorption in
      combination with gas chromatography-ion trap tandem mass spectrometry. The
      analytical method proposed was easy, rapid and sensitive and showed good
      linearity, accuracy, repeatability and reproducibility over the concentration
      range tested. Moreover, the correlation coefficients were higher than 0.98 for
      all target compounds and detection limits were lower than 1 microg/kg except for
      simazine. The present method was also applied for the analysis of trace
      contaminants in saffron samples.

PMID- 18817916
TI  - Preparation and characterization of poly(l-phenylalanine) chiral stationary
      phases with varying peptide length.
AB  - Three new chiral stationary phases with different lengths of l-phenylalanine
      peptide were prepared by solid-phase synthesis with tert-butoxycarbonyl (Boc)-l
      phenylalanine on silica. The effect of phenylalanine peptide length on
      enantioselectivity was studied. The best separation of R/S-warfarin was achieved
      by the chiral stationary phase with intermediate peptide length. These stationary
      phases were found to exist mainly in alpha-helical conformation by using FT-IR
      spectra. The end-capping reagents for the N-terminus of the peptide were also
      evaluated.

PMID- 18817917
TI  - Synthesis of succinimidyl-(S)-naproxen ester and its application for indirect
      enantioresolution of penicillamine by reversed-phase high-performance liquid
      chromatography.
AB  - Synthesis of N-succinimidyl-(S)-2-(6-methoxynaphth-2-yl) propionate was carried
      out by the reaction of (S)-naproxen with N-hydroxysuccinimide in the presence of
      dicyclohexyl carbodiimide. It was characterized and was used as a chiral
      derivatizing reagent, under mild conditions, to form diastereomers of dl
      penicillamine which were resolved by reversed-phase high-performance liquid
      chromatography using triethyl ammonium phosphate buffer (pH 4.0, 5mM)
      acetonitrile (linear gradient (30min) of acetonitrile from 30 to 70%). Excellent
      separation was achieved with gradient mobile phase. The detection limit was at
      pmol level.

PMID- 18817918
TI  - Improved liquid chromatography-Online radioactivity detection for metabolite
      profiling.
AB  - If very-high-pressure liquid chromatography (VHPLC) is to replace conventional
      HPLC as the ultimate separation tool for metabolism studies in development,
      coupling it efficiently with online radioactivity detection (RAD) is needed. We
      describe the successful combination of VHPLC/RAD, facilitated by improvements in
      online radioactivity detection, as well as in column loading and peak capacity.
      The sensitivity of (14)C detection was improved by the use of a variable
      scintillation flow achieved via a simple modification to the classical online
      radiochemical detection set-up. A modification of the flow-through cell design in
      which internal diameter of the tubing was reduced further increased the
      sensitivity and resolution by decreasing peak tailing. The injection of
      relatively large injection volumes was made possible by the use of columns packed
      at ultra-high pressure with 2.2 microm particles. Because of the reduced back
      pressure generated using these larger particle sizes, two 150 mm x 3 mm columns
      could be coupled, allowing 4-fold larger injection volumes and a 50% increase in
      theoretical plate number at a similar back pressure compared to a standard 150 mm
      x 2.1mm Waters UPLC column. The value of the methodology described was
      demonstrated by the analysis of in vitro and in vivo metabolism samples of (3)H-
      and (14)C-labeled compounds and compared with conventional radio-HPLC. We have
      shown that metabolite separation can be achieved with increased efficiency while
      maintaining a sensitivity comparable to that of conventional HPLC/RAD.

PMID- 18817919
TI  - Determination of trihalomethanes in waters by ionic liquid-based single drop
      microextraction/gas chromatographic/mass spectrometry.
AB  - A simple, rapid, solventless method for the determination of trihalomethanes
      (THMs) (chloroform, bromodichloromethane, dibromochloromethane and bromoform) in
      water samples is presented. The analytes are extracted from the headspace of the
      aqueous matrix into a 2 microL drop of the ionic liquid 1-octyl-3-methyl
      imidazolium hexafluorophosphate working at 30 degrees C for 30 min. The
      separation and detection of the target compounds is accomplished by gas
      chromatography/mass spectrometry owing to the use of an interface that
      efficiently transfers the analytes extracted in the ionic liquid drop to the gas
      chromatograph while preventing the ionic liquid from entering the column. The
      detection limits obtained are below the values compelled by the legislation,
      ranging from 0.5 microg L(-1) for chloroform and bromodichloromethane to 0.9
      microg L(-1) for dibromochloromethane. The use of ionic liquid in the extraction
      procedure avoids the use of organic solvents and leads to relative standard
      deviations that range from 3.1% to 4.8%.

PMID- 18817920
TI  - Gastric neuroendocrine carcinoma associated with atrophic gastritis in the
      norwegian lundehund.
AB  - In humans and rodents the association between atrophic gastritis,
      hypergastrinemia and gastric neoplasia is well-documented. Gastric tumours are
      rare in dogs, but the Norwegian Lundehund (puffin dog) appears predisposed to the
      development of gastric neoplasia associated with chronic atrophic gastritis. The
      present study describes 8 Lundehunds with gastric neoplasia. Seven of these
      animals had concurrent chronic atrophic gastritis characterized by reduction in
      parietal cells and hyperplasia of neuroendocrine cells. Four of the tumours
      displayed neuroendocrine (enterochromaffin-like cell; ECL) differentiation,
      suggesting that hypergastrinemia secondary to fundic atrophy may be important in
      carcinogenesis. The Norwegian Lundehund may therefore represent a further animal
      model for the study of the role of gastrin in the induction of gastric neoplasia.

PMID- 18817921
TI  - Where do derived precordial leads fail?
AB  - A 12-lead electrocardiogram (ECG) reconstructed from a reduced subset of leads is
      desired in continued arrhythmia and ST monitoring for less tangled wires and
      increased patient comfort. However, the impact of reconstructed 12-lead lead ECG
      on clinical ECG diagnosis has not been studied thoroughly. This study compares
      the differences between recorded and reconstructed 12-lead diagnostic ECG
      interpretation with 2 commonly used configurations: reconstruct precordial leads
      V(2), V(3), V(5), and V(6) from V(1),V(4), or reconstruct V(1), V(3), V(4), and
      V(6) from V(2),V(5). Limb leads are recorded in both configurations. A total of
      1785 ECGs were randomly selected from a large database of 50,000 ECGs
      consecutively collected from 2 teaching hospitals. ECGs with extreme artifact and
      paced rhythm were excluded. Manual ECG annotations by 2 cardiologists were
      categorized and used in testing. The Philips resting 12-lead ECG algorithm was
      used to generate computer measurements and interpretations for comparison.
      Results were compared for both arrhythmia and morphology categories with high
      prevalence interpretations including atrial fibrillation, anterior myocardial
      infarct, right bundle-branch block, left bundle-branch block, left atrial
      enlargement, and left ventricular hypertrophy. Sensitivity and specificity were
      calculated for each reconstruction configuration in these arrhythmia and
      morphology categories. Compared to recorded 12-leads, the V(2),V(5) lead
      configuration shows weakness in interpretations where V(1) is important such as
      atrial arrhythmia, atrial enlargement, and bundle-branch blocks. The V(1),V(4)
      lead configuration shows a decreased sensitivity in detection of anterior
      myocardial infarct, left bundle-branch block (LBBB), and left ventricular
      hypertrophy (LVH). In conclusion, reconstructed precordial leads are not
      equivalent to recorded leads for clinical ECG diagnoses especially in ECGs
      presenting rhythm and morphology abnormalities. In addition, significant accuracy
      reduction in ECG interpretation is not strongly correlated with waveform
      differences between reconstructed and recorded 12-lead ECGs.

PMID- 18817922
TI  - Study of surface electrocardiogram spectrum before and after pulmonary vein
      ablation in patients with persistent atrial fibrillation.
AB  - Atrial fibrillation (AF) is the most common clinical cardiac arrhythmia and is
      usually treated with the electrical isolation of the pulmonary veins from the
      atria. However, it is estimated that about 30% of the patients undergoing this
      therapy will develop AF again. The purpose of this study was to test the dynamic
      changes of the spectra calculated in surface electrocardiograms (ECGs) before and
      after the ablation of the pulmonary veins. Surface ECGs of 14 patients with
      persistent AF undergoing this intervention were considered for this study. The
      QRS-T waves were subtracted from the ECGs using common spatial pattern, isolating
      the electrical activity of the atrium. The spectrum was then calculated and the
      main frequency peaks were identified. The smaller peaks with amplitude below 50%
      of the maximum were discarded. Eleven of the patients were followed up after the
      intervention for 1 to 6 months. Two of the patients developed AF again; the other
      9 remained in sinus rhythm. For most of the patients, the spectrum showed more
      order after the intervention. However, the main frequency did not experience a
      significant decrease in average (5.1 Hz [+/-1.3] to 4.9 Hz [+/-1.0]).
      Interestingly, the increment or decrease of the main frequency did not correlate
      with the recurrence of AF or not.

PMID- 18817923
TI  - Normal limits of the spatial QRS-T angle and ventricular gradient in 12-lead
      electrocardiograms of young adults: dependence on sex and heart rate.
AB  - BACKGROUND AND PURPOSE: Normal limits of the spatial QRS-T angle and spatial
      ventricular gradient (SVG) are only available from Frank vectorcardiograms (VCGs)
      of male subjects. We determined normal limits for these variables derived from
      standard 12-lead electrocardiograms (ECGs) of 660 male and female students aged
      18 to 29 years. METHODS: A computer algorithm was used that constructed
      approximated VCG leads by inverse Dower matrix transformation of the 12-lead ECG
      and subsequently calculated the spatial QRS-T angle, SVG magnitude, and
      orientation. RESULTS: In female subjects, the QRS-T angle was more acute
      (females, 66 degrees +/- 23 degrees; normal, 20 degrees-116 degrees; males, 80
      degrees +/- 24 degrees; normal, 30 degrees-130 degrees; P < .001), and the SVG
      magnitude was smaller (females, 81 +/- 23 mV x ms; normal, 39-143 mV x ms; males,
      110 +/- 29 mV x ms; normal, 59-187 mV x ms; P < .001) than in male subjects. The
      male SVG magnitude in our study was larger than that computed in Frank VCGs (79
      +/- 28 mV.ms; P < .001). CONCLUSIONS: The spatial QRS-T angle and SVG depend
      strongly on sex. Furthermore, normal limits of SVG derived from Frank VCGs differ
      markedly from those derived from VCGs synthesized from the standard ECG. As
      nowadays, VCGs are usually synthesized from the 12-lead ECG; normal limits
      derived from the standard ECG should preferably be used.

PMID- 18817924
TI  - An early phase of slow myocardial activation may be necessary in order to benefit
      from cardiac resynchronization therapy.
AB  - BACKGROUND: Not all patients with a QRS duration longer than 140 milliseconds
      respond to cardiac resynchronization therapy (CRT). The same QRS duration may
      correspond to different spatiotemporal patterns of myocardial activation that
      influence response to CRT. METHODS: Electrocardiographic imaging based on 80
      chest wall electrodes was used to construct the spatiotemporal myocardial
      activation map in 46 consecutive patients before CRT. The cumulative percentage
      of myocardium activated was plotted against time expressed in terms of quintiles
      of the overall QRS duration. Changes in the left ventricular ejection fraction
      and end-diastolic diameter, maximum oxygen consumption per minute, brain
      natriuretic peptide level, and 6-minute walk distance after 6 months of CRT were
      compared across different patterns with 1-way analysis of variance. RESULTS: Data
      from 34 patients were available for analysis. Four spatiotemporal patterns of
      myocardial activation could be identified: triphasic (fast-slow-fast) (13),
      uniform (8), fast-slow (7), and slow-fast (6). The overall QRS duration was
      similar in the 4 groups (166 +/- 19 vs 138 +/- 21 vs 157 +/- 26 vs 152 +/- 37
      milliseconds, P = not significant [NS]). The ejection fraction showed a trend of
      greater increases for the triphasic (6.5% +/- 7.0%) and slow-fast (15.5% +/-
      6.4%) patterns than for the uniform (4.0% +/- 13.3%) and fast-slow (8.0% +/-
      6.1%) patterns (P = NS). The end-diastolic diameter showed a trend of greater
      decreases for the triphasic (-3.7% +/- 5.3%) and slow-fast (-7.0% +/- 6.7%)
      patterns than for the uniform (0.8% +/- 6.7%) and fast-slow (0.0% +/- 4.6%)
      patterns (P = NS). The maximum oxygen consumption per minute showed a trend of
      greater increases for the triphasic (1.2 +/- 4.2 mL/kg/min) and slow-fast (4.1 +/
      2.7 mL/kg/min) patterns than for the uniform (0.1 +/- 4.1 mL/kg/min) and fast
      slow (1.0 +/- 2.1 mL/kg/min) patterns (P = NS). The brain natriuretic peptide
      level decreased significantly more for the triphasic (-450 +/- 1269) and slow
      fast (-3121 +/- 1512) patterns than for the uniform (762 +/- 1036) and fast-slow
      (718 +/- 2530) patterns (P = .0003). The 6-minute walk distance increased
      significantly more for the triphasic (29 +/- 89) and slow-fast (40 +/- 23)
      patterns than for the uniform (6 +/- 87) and fast-slow (37 +/- 45) patterns (P =
      .0003). CONCLUSIONS: Different spatiotemporal patterns of myocardial activation
      exist among patients with broad QRS complex and may affect response to CRT. An
      early phase of slow myocardial activation (the triphasic fast-slow-fast and the
      slow-fast patterns) may be necessary for a patient to benefit from CRT.

PMID- 18817925
TI  - Subject-specific heart rate dependency of electrocardiographic QT, PQ, and QRS
      intervals.
AB  - Although heart rate dependency of QT interval is well known, the relationship of
      other electrocardiogram (ECG) parameters to heart rate has been researched less
      intensively. This study investigated the heart rate dependencies of QT interval,
      PQ interval, and QRS width in 40 healthy subjects (18 women; mean age, 30.4 +/-
      8.1 years). In each subject, 3 long-term (approximately 13 hours) 12-lead ECGs
      were obtained for 3 day-time periods with gaps of 2 to 3 weeks between repeated
      recordings. In each recording, approximately 230 ECG measurements of QT interval,
      PQ interval, and QRS width were made, each preceded by stable heart rate. For
      each recording, linear regression slopes of QT/RR, PQ/RR, and QRS/RR
      relationships were obtained. Intrasubject SDs of individual values were compared
      with intersubject SDs of intrasubject means to test the individuality of the
      relationships. The intrasubject means of the slope values were also compared
      between sexes. The individual SDs of the QT/RR regression slopes were 0.0116 +/-
      0.0065, whereas the population SD of intrasubject means was 0.0245 (P = 3.6 x 10(
      15)). For the PQ/RR slopes and QRS/RR slopes, these values were 0.0085 +/- 0.0050
      vs 0.0314 (P = 7.9 x 10(-28)) and 0.00189 +/- 0.00157 vs 0.00550 (P = 2.6 x 10(
      17)), respectively. The QT/RR slopes were steeper in women than in men (0.194 +/-
      0.019 vs 0.168 +/- 0.022, 0.0005), whereas the QRS/RR slopes were, on average,
      negative in women while positive in men (-0.00138 +/- 0.0045 vs 0.00335 +/-
      0.0054, P = .005). There were no sex differences in the PQ/RR slopes (0.054 +/-
      0.032 in women vs 0.055 +/- 0.031 in men, P = .95). Thus, not only the heart rate
      dependency of QT interval but also the rate dependencies of PQ interval and of
      QRS width show high intrasubject stability with substantial intersubject
      differences.

PMID- 18817926
TI  - Predictive modeling of defibrillation using hexahedral and tetrahedral finite
      element models: recent advances.
AB  - Implanted cardioverter/defribillator (ICD) implants may be complicated by body
      size and anatomy. One approach to this problem has been the adoption of creative,
      extracardiac implant strategies using standard ICD components. Because data on
      safety or efficacy of such ad hoc implant strategies are lacking, we have
      developed image-based finite element models to compare electric fields and
      expected defibrillation thresholds (DFTs) using standard and novel electrode
      locations. In this article, we review recently published studies by our group
      using such models and progress in meshing strategies to improve efficiency and
      visualization. Our preliminary observations predict that they may be large
      changes in defibrillation thresholds with clinically relevant variations of
      electrode placement. Extracardiac ICDs of various lead configurations are
      predicted to be effective in both children and adults. This approach may aid both
      ICD development and patient-specific optimization of electrode placement, but the
      simplified nature of current models dictates further development and validation
      before clinical or industrial use.

PMID- 18817927
TI  - Magnetic resonance imaging as a potential gold standard for infarct
      quantification.
AB  - Accurate diagnosis, characterization, and quantification of myocardial infarction
      (MI) is essential to assess the impact of therapy and to aid in predicting
      prognosis of patients with ischemic heart disease. Delayed contrast-enhanced
      magnetic resonance (DE-MR) imaging has the potential of being the gold standard
      for quantification of MI. It has also been useful in correlating
      electrocardiography abnormalities with the location and transmurality of
      infarction. The focus of this review is to address the strengths and limitations
      of DE-MR imaging in the detection and quantification of MI for clinicians and
      investigators in the field of electrocardiology. The biological rationale and
      technical background for detecting MI by DE-MR imaging were reviewed as well as
      the different approaches for quantification of the DE-MR images, exemplified by
      patient cases.

PMID- 18817928
TI  - Standardization of reduced and optimal lead sets for continuous electrocardiogram
      monitoring: where do we stand?
AB  - Mason-Likar or proprietary reduced lead (RL) configurations are used for
      continuous 12-lead electrocardiogram (ECG) monitoring. Because each RL set has a
      different electrode configuration and derivation, they are inherently different
      and should not be compared with each other or with the Mason-Likar or standard
      ECG to determine changes in an individual over time. Recently, cases have been
      reported regarding misdiagnosis resulting from such invalid comparisons. This
      article addresses several relevant questions and presents data collected from 559
      subjects (one third, prior myocardial infarction; one third, left ventricular
      hypertrophy; one third, healthy controls) comparing standard limb leads with body
      surface potential map (BSPM) leads. We conclude the following: (1) There are few
      circumstances that justify the use of RL 12-lead ECGs; the convenience should be
      weighed by the risk of misdiagnosis resulting from serial comparison of
      nonequivalent ECGs. (2) When RL monitoring is justified, standardization of one
      universally adopted method would reduce confusion about multiple proprietary lead
      configurations and minimize invalid ECG comparisons in individuals treated in
      multiple hospital units with different manufacturers' cardiac monitors. (3)
      Standard limb lead P-QRS-T waveforms correlate highly with BSPM leads located
      outside standard unipolar precordial lead sites. Until it is clear that "optimum"
      BSPM lead sites do not overlap with ECG information already contributed from
      standard limb leads, it is premature to recommend alternative lead sites for ECG
      monitoring.

PMID- 18817929
TI  - Motor alterations are reduced in mice lacking the PARK2 gene in the presence of a
      human FTDP-17 mutant form of four-repeat tau.
AB  - Independent deletion of the PARK2 gene and hTauVLW over-expression in mice
      produce mild alterations in the brain. However, the presence of both mutations in
      a parkin-deficient and hTauVLW double mutant mouse causes a tau neuropathology,
      reactive astrocytosis, and neuronal loss in the cortex and hippocampus, as well
      as lesions in nigrostriatal and motor neurons. Moreover, these mutants display
      some memory and exploratory defects that reflect a functional link between parkin
      and tau proteins. We have tested the motor activity and coordination of these
      double mutant mice to determine the effects of parkin deletion in mice over
      expressing the hTauVLW transgene. While the loss of parkin alone produces
      increased exploration and alterations in gait and motor coordination, in hTauVLW
      transgenic mice the absence of parkin causes less prominent motor impairments.
      These effects suggest the existence of some compensatory mechanisms that are
      activated when the hTauVLW transgene is over-expressed in the absence of parkin.
      This mouse model will hopefully help to study the causes of the motor deficits
      associated with certain neuropathologies related to the tau and parkin proteins,
      and to find appropriate treatments.

PMID- 18817930
TI  - Single dose of methylphenidate improves cognitive performance in multiple
      sclerosis patients with impaired attention process.
AB  - BACKGROUND AND PURPOSE: Attention is one of the major cognitive domains adversely
      affected in multiple sclerosis (MS). The aim of the current study was to
      determine the effect of a single dose of methylphenidate on cognitive performance
      of MS patients with significant attention deficit. METHODS: In a double-blind
      placebo-controlled study design, 26 MS patients with impaired attention were
      randomly assigned to receive a single dose of 10 mg methylphenidate or placebo.
      Attention was assessed using the paced auditory serial addition test for 3 and 2
      s (PASAT3'' and PASAT2'') at baseline and 1 h after drug/placebo administration.
      RESULTS: Methylphenidate significantly improved performance of both PASAT3'' and
      PASAT2'' tests by 22.8% and 25.6% respectively (p<0.001), while no significant
      changes were observed in placebo treated patients. CONCLUSION: Administration of
      a single dose of methylphenidate significantly improved attention in MS patients
      with considerable attention deficit.

PMID- 18817931
TI  - Biomarkers of environmental toxicity and susceptibility in autism.
AB  - Autism spectrum disorders (ASDs) may result from a combination of
      genetic/biochemical susceptibilities in the form of a reduced ability to excrete
      mercury and/or increased environmental exposure at key developmental times.
      Urinary porphyrins and transsulfuration metabolites in participants diagnosed
      with an ASD were examined. A prospective, blinded study was undertaken to
      evaluate a cohort of 28 participants with an ASD diagnosis for Childhood Autism
      Rating Scale (CARS) scores, urinary porphyrins, and transsulfuration metabolites.
      Testing was conducted using Vitamin Diagnostics, Inc. (CLIA-approved) and
      Laboratoire Philippe Auguste (ISO-approved). Participants with severe ASDs had
      significantly increased mercury intoxication-associated urinary porphyrins
      (pentacarboxyporphyrin, precoproporphyrin, and coproporphyrin) in comparison to
      participants with mild ASDs, whereas other urinary porphyrins were similar in
      both groups. Significantly decreased plasma levels of reduced glutathione (GSH),
      cysteine, and sulfate were observed among study participants relative to
      controls. In contrast, study participants had significantly increased plasma
      oxidized glutathione (GSSG) relative to controls. Mercury intoxication-associated
      urinary porphyrins were significantly correlated with increasing CARS scores and
      GSSG levels, whereas other urinary porphyrins did not show these relationships.
      The urinary porphyrin and CARS score correlations observed among study
      participants suggest that mercury intoxication is significantly associated with
      autistic symptoms. The transsulfuration abnormalities observed among study
      participants indicate that mercury intoxication was associated with increased
      oxidative stress and decreased detoxification capacity.

PMID- 18817932
TI  - Reconsidering clinical outcomes in Multiple Sclerosis: relapses, impairment,
      disability and beyond.
AB  - There is an increasing number of clinical trials testing new compounds which act
      at different stages of Multiple Sclerosis (MS). To prove their effectiveness
      several clinical outcome measures are used. The overall quality of clinical
      trials is increasing steadily due to the growing experience in this area, the
      increasing awareness of quality standards in the MS community and the more
      stringent requirements of regulatory authorities for approval of new treatments.
      Each successful clinical trial provided additional information that could be
      incorporated into the design of subsequent studies to improve their quality.
      However, the choice of appropriate outcome measures still presents major
      challenges. For an individual patient improvement or stability of their
      disability and to a lesser extent the relapse rate, are the main targets of
      treatment. As there is yet no scale or assessment, which objectively covers all
      major issues, it is recommended to use multiple instruments and endpoints as
      secondary outcome measures.

PMID- 18817933
TI  - Hemispatial neglect in cerebellar stroke.
AB  - Cognitive deficits can be associated with cerebellar injury. The purpose of this
      study is to learn 1) if unilateral cerebellar injury might also cause hemispatial
      neglect, and if so, 2) if there is a left versus right asymmetry, 3) if the
      neglect is contralesional (CN) or ipsilesional (IN), and 4) if cerebellar injury
      might induce neglect by disruption of cerebellar-cortical networks. Participants
      were 28 patients with unilateral cerebellar stroke who were assessed for neglect
      within 2 months after the onset of stroke. To investigate if the cerebellar
      cerebral network dysfunction induced neglect, 12 patients received perfusion
      single photon emission computed tomography (SPECT). Eight of the participants
      demonstrated neglect (28.6%), four with left cerebellar strokes (three with CN
      and one with IN) and four with right cerebellar strokes (three with IN and one
      with CN). Among five patients with neglect who had undergone SPECT, only one with
      ipsilesional neglect showed crossed cerebello-cerebral diaschisis. Neglect
      induced by cerebellar stroke might be more common than previously reported. Based
      on the cerebellar-cerebral network hypothesis we expected neglect to be more
      common with left than right cerebellar injury, but there was an equal number of
      patients with neglect from right and left sided strokes and the SPECT scan did
      not provide support of this hypothesis. Thus, this hypothesis cannot also explain
      the equal number of subject with ipsi- and contralesional neglect and in future
      studies alternative hypotheses such as vestibular hypothesis will have to be
      explored.

PMID- 18817934
TI  - Best practice statement on cryosurgery for the treatment of localized prostate
      cancer.

PMID- 18817935
TI  - A general integrated ecotoxicological method for marine sediment quality
      assessment: application to sediments from littoral ecosystems on Southern Spain's
      Atlantic coast.
AB  - In the last few decades, several integrated methods for marine sediment quality
      evaluation have been developed and applied to many coastal sites. This paper
      describes the development of a general integrated method based on the
      determination of organic and inorganic sediment contamination, lethal and
      sublethal toxicity assessments, in situ benthonic community structure alteration
      and bioaccumulation of contaminants. The proposed method was applied to sediments
      from Southern Spain's Atlantic coast where six rivers (Guadiana, Carreras,
      Piedras, Tinto, Odiel and Guadalquivir) drain pollutants from various
      anthropogenic sources. A series of experiments was conducted to determine the
      characteristics of the sediments: granulometry, organic matter content, etc. (1);
      metal contamination of sediments and Chamelea gallina (bivalves widely
      distributed in the area studied) (2); lethal and sublethal toxicity by a series
      of biological tests (3); and macrofauna distribution at the 16 stations included
      in the study (4). Ratio-to-reference values (RTR) calculated for each parameter
      were used to determine the organic and inorganic contamination indices, the
      lethal and sublethal toxicity indices, the index of bioavailability of metals in
      the organisms analyzed and the macrobenthic alteration index. The data were
      plotted on six-axis plots to describe better the relations between the physical,
      chemical and biological properties studied. A general integrated sediment quality
      index (ISQI) was determined and used as an indicator of pollution-induced
      degradation. The ISQI values summarize the main characteristics of the
      environmental situation at each sampling point and can be used for purposes of
      comparison.

PMID- 18817936
TI  - [Intramedullary tuberculoma of the conus: a case report].
AB  - Tuberculomas of the spinal cord are rare. The objective of this study was to
      illustrate the diagnosis and treatment of tuberculomas of the conus medullaris.
      They must be suspected in patients with a clinical context and a typical spinal
      cord mass lesion. Treatment is primarily medical. Surgery is reserved for cases
      of rapid neurological deterioration or doubts concerning the diagnosis. We report
      a case of intramedullary tuberculoma of the conus in a 27-year-old woman with
      paresthesias and weakness of the lower limbs who had been treated for pulmonary
      tuberculosis. The spinal MR showed a characteristic intramedullary ring-enhancing
      lesion. She improved neurologically one month after the beginning of the
      antituberculous drugs and a laminectomy. Seven months later, the patient is
      asymptomatic and the lesion has nearly completely disappeared completely.

PMID- 18817937
TI  - [Extradural spinal meningioma: case report].
AB  - OBJECTIVES: We report a case of purely extradural spinal meningioma and discuss
      the potential pitfalls in differential diagnosis. BACKGROUND: Spinal meningiomas
      account for 20-30% of all spinal neoplasms. Epidural meningiomas are infrequent
      intraspinal tumors that can be easily confused with malignant neoplasms or spinal
      schwannomas. CASE: A 62-year-old man with a previous history of malignant disease
      presented with back pain and weakness of the lower limbs. Magnetic resonance
      imaging revealed a well-enhanced T4 intraspinal lesion. The intraoperative
      histological examination showed a meningioma (confirmed by postoperative
      examination). Opening the dura mater confirmed the purely epidural location of
      the lesion. The postoperative course was uneventful with no recurrence 12 months
      after surgery. CONCLUSION: Purely extradural spinal meningiomas can mimic
      metastatic tumors or schwannomas. Intraoperative histology is mandatory for
      optimal surgical decision making.

PMID- 18817938
TI  - Potential anti-allergic acridone alkaloids from the roots of Atalantia
      monophylla.
AB  - Acridone alkaloids, cycloatalaphylline-A (1), N-methylcyclo-atalaphylline-A (2)
      and N-methylbuxifoliadine-E (3), were isolated from the dichloromethane and
      acetone extracts of the root of Atalantia monophylla along with eight known
      acridone alkaloids: buxifoliadine-A (4), buxifoliadine-E (5), N
      methylatalaphylline (6), atalaphylline (7), citrusinine-I (8), N
      methylataphyllinine (9), yukocitrine (10) and junosine (11) and two known
      coumarins: auraptene (12) and 7-O-geranylscopoletin (13). Their structures were
      elucidated on the basis of spectroscopic analyses. Compounds 2, 5 and 8 possessed
      appreciable anti-allergic activity in RBL-2H3 cells model with IC(50) values of
      40.1, 6.1 and 18.7 microM, respectively.

PMID- 18817939
TI  - [Postictal psychosis syndrome: a clinical entity to be recognized].
AB  - INTRODUCTION: Post-ictal psychosis syndrome (PIP) belongs to the group of
      epileptic psychoses which, according to the most commonly used classification, is
      to be distinguished from ictal psychoses, on one hand, and from inter-ictal
      psychoses, on the other. OBJECTIVES: The present paper aims to review recent data
      concerning the clinical, therapeutic and pathophysiological aspects of PIP.
      METHODS: We report four cases of PPI, which involved four patients hospitalized
      at the Salpetriere hospital between 2001 and 2005, and discuss these cases in
      light of the relevant literature. RESULTS: The PIP fit generally occurs in
      patients suffering from intractable temporal lobe epilepsy which started several
      years before. The psychiatric disorders suddenly take hold after a series of
      complex partial seizures with frequent secondarily generalized tonic clonic
      seizures. During the episode, EEG recordings do not show any epileptic activity.
      Psychiatric symptoms consist of persecutory delusive ideas, verbal and visual
      hallucinations, agitation, and aggressiveness. Mood disorders are variable from
      one patient to another and exhibit intraindividual fluctuation. In most patients
      given antipsychotic drugs, the short-term outcome of PIP is favorable . In the
      long-term, even if recurrence is the main long-term risk, progression to severe
      mood disorders or to poor prognosis inter-ictal psychosis is possible.
      Accordingly, the clinician must be aware of this syndrome in order to correctly
      diagnose PIP since effective treatment with antipsychotic drugs is available.
      CONCLUSION: The short-term prognosis of PPI is usually favorable but this
      syndrome can potentially develop in the long-term to more severe psychiatric
      disorders. It is, therefore, important to recognize PIP syndromes which respond
      more readily to pharmacological treatments than other types of psychoses.

PMID- 18817940
TI  - Public health importance of non-biting cyclorrhaphan flies.
AB  - This study was carried out to determine the role of non-biting cyclorrhaphan
      flies as carriers of human intestinal parasites at Woreta, northwestern Ethiopia.
      In total, 6530 flies were collected from four breeding sites and then examined
      for human intestinal parasites, mainly using the formol-ether concentration
      method. Fly species identified were Musca domestica (32.9%), Chrysomya rufifacies
      (32.6%), Musca sorbens (23%), Lucina cuprina (4.7%), Calliphora vicina (2.8%),
      Chrysomya bezziana (2.3%) and Wohlfahrtia magnifica (1.7%). Intestinal parasites
      such as Ascaris lumbricoides (36.9%), Trichuris trichiura (38.8%), hookworm
      (13.0%), Hymenolepis nana (0.6%), Taenia spp. (8.4%), Strongyloides stercoralis
      (1.7%), Entamoeba histolytica/dispar (48.1%), Entamoeba coli (24.7%),
      Cryptosporidium spp. (16.7%) and Giardia lamblia (10.4%) were isolated from both
      external and gut contents of the flies. Trichuris trichiura and A. lumbricoides
      among the helminths and E. histolytica/dispar and E. coli among the protozoans
      were the dominant parasites identified. It was observed that more parasites were
      isolated from gut contents than the external surfaces of the flies examined
      (P<0.001). Chrysomya rufifacies were found to carry more helminths than M.
      sorbens and M. domestica. Musca sorbens were the highest carriers of protozoan
      parasites followed by M. domestica and C. rufifacies. The significance of filth
      flies as carriers of human intestinal parasites has been highlighted.

PMID- 18817941
TI  - Biotransformation of arsenic species by activated sludge and removal of bio
      oxidised arsenate from wastewater by coagulation with ferric chloride.
AB  - The potential of activated sludge to catalyse bio-oxidation of arsenite [As(III)]
      to arsenate [As(V)] and bio-reduction of As(V) to As(III) was investigated. In
      batch experiments (pH 7, 25 degrees C) using activated sludge taken from a
      treatment plant receiving municipal wastewater non-contaminated with As, As(III)
      and As(V) were rapidly biotransformed to As(V) under aerobic condition and
      As(III) under anaerobic one without acclimatisation, respectively. Sub-culture of
      the activated sludge using a minimal liquid medium containing 100mg As(III)/L and
      no organic carbon source showed that aerobic arsenic-resistant bacteria were
      present in the activated sludge and one of the isolated bacteria was able to
      chemoautotrophically oxidise As(III) to As(V). Analysis of arsenic species in a
      full-scale oxidation ditch plant receiving As-contaminated wastewater revealed
      that both As(III) and As(V) were present in the influent, As(III) was almost
      completely oxidised to As(V) after supply of oxygen by the aerator in the
      oxidation ditch, As(V) oxidised was reduced to As(III) in the anaerobic zone in
      the ditch and in the return sludge pipe, and As(V) was the dominant species in
      the effluent. Furthermore, co-precipitation of As(V) bio-oxidised by activated
      sludge in the plant with ferric hydroxide was assessed by jar tests. It was shown
      that the addition of ferric chloride to mixed liquor as well as effluent achieved
      high removal efficiencies (>95%) of As and could decrease the residual total As
      concentrations in the supernatant from about 200 microg/L to less than 5
      microg/L. It was concluded that a treatment process combining bio-oxidation with
      activated sludge and coagulation with ferric chloride could be applied as an
      alternative technology to treat As-contaminated wastewater.

PMID- 18817942
TI  - Inappropriate use of the term 'oncocytic lipoadenoma of the submandibular gland'.

PMID- 18817943
TI  - Endocranial volumes of primate species: scaling analyses using a comprehensive
      and reliable data set.
AB  - We present a compilation of endocranial volumes (ECV) for 176 non-human primate
      species based on individual data collected from 3813 museum specimens, at least
      88% being wild-caught. In combination with body mass data from wild individuals,
      strong correlations between endocranial volume and body mass within taxonomic
      groups were found. Errors attributable to different techniques for measuring
      cranial capacity were negligible and unbiased. The overall slopes for regressions
      of log ECV on log body mass in primates are 0.773 for least-squares regression
      and 0.793 for reduced major axis regression. The least-squares slope is reduced
      to 0.565 when independent contrasts are substituted for species means (branch
      lengths from molecular studies). A common slope of 0.646 is obtained with logged
      species means when grade shifts between major groups are taken into account using
      ANCOVA. In addition to providing a comprehensive and reliable database for
      comparative analyses of primate brain size, we show that the scaling relationship
      between brain mass and ECV does not differ significantly from isometry in
      primates. We also demonstrate that ECV does not differ substantially between
      captive and wild samples of the same species. ECV may be a more reliable
      indicator of brain size than brain mass, because considerably larger samples can
      be collected to better represent the full range of intraspecific variation. We
      also provide support for the maternal energy hypothesis by showing that basal
      metabolic rate (BMR) and gestation period are both positively correlated with
      brain size in primates, after controlling for the influence of body mass and
      potential effects of phylogenetic relatedness.

PMID- 18817944
TI  - The essential toxin: the changing perception of selenium in environmental
      sciences.
AB  - During the last decades, the perception of selenium has undergone substantial
      changes. While its toxic effects were recognized causing hair and hoof loss in
      animals during the 1930s, its essential role in microbial, animal and human
      metabolism has been recognized later, i.e. with the discovery of selenium
      deficiency causing "white muscle disease" in feedstock in the 1950s. Nowadays,
      the positive effect of systematic selenium supplementation is discussed in
      manifold topics such as cancer or diabetes prevention and avian influenza
      susceptibility. Treatment of selenium containing waste streams poses a notable
      challenge to environmental engineers, and to date no ultimate solution has been
      found for e.g. the selenium contamination in agricultural areas of the western
      USA. For the future, selenium contamination carries an imminent danger, if the
      increasing energy demand is covered by fossil fuel combustion, which will lead to
      major selenium emission and toxicity. This review presents current knowledge of
      selenium's role in environmental sciences and outlines potentially feasible
      treatment options targeting a variety of selenium contaminated waste streams.

PMID- 18817945
TI  - Effect of dietary methylmercury and seleno-methionine on Sacramento splittail
      larvae.
AB  - The effects of methylmercury (MeHg) and selenium (Se) contamination on food webs
      in the San Francisco Estuary have received considerable attention during the past
      decade. However, knowledge of their effects on native fishes of California is
      lacking. This study investigated the interactive effects of dietary MeHg and
      seleno-methionine (SeMet) on Sacramento splittail (Pogonichthys macrolepidotus)
      larvae. Twelve diets containing increasing levels of SeMet (0.64, 8.2 and 35.0
      microg Se g(-1) diet) and MeHg (0.01, 0.13, 4.7 and 11.7 microg Hg g(-1) diet)
      were fed to 21-day post-hatch larvae for 4 weeks in 2-L beakers at 25 degrees C.
      Fish were fed twice a day at a feeding rate of 40, 30, 25 and 20% of body weight
      during the 1st, 2nd, 3rd and 4th week, respectively. At the end of week 4, no
      significant difference (P>0.05) was observed among treatments for mortality, body
      length or weight, and condition factor. Bioaccumulation of Hg and Se responded
      positively and significantly (P<0.05) to their dietary concentrations. The molar
      ratio of Se/Hg in diets was linearly correlated to the ratio of Se/Hg in fish.
      Dietary Se inhibited Hg accumulation, which was negatively correlated to the
      dietary Se/Hg ratio. Histopathological examination revealed severe gill anomaly
      and liver glycogen depletion in fish fed the 11.7 microg Hg g(-1) diet. Liver
      glycogen depletion and kidney tubular dilation were found in larvae fed the 11.7
      microg Hg and 11.7 microg Hg+35 microg Se g(-1) diets. In conclusion, dietary Hg
      enhanced Se accumulation but dietary Se inhibited Hg accumulation in splittail.
      Dietary Se showed a protective effect in fish fed the high MeHg diet. This
      protection was related to the dietary Se/Hg ratio, which is a more reliable
      criterion for evaluating the interactive effect between Se and Hg in splittail.

PMID- 18817946
TI  - Monitoring mercury in two South African herbaria.
AB  - Mercury [Hg] emissions from old plant collections treated with mercuric chloride
      (HgCl(2)) may present a high health risk for staff working in certain herbaria.
      The present study evaluated Hg concentrations in ambient air, plant specimens and
      biological samples from staff working in the Pretoria National Herbarium (PRE)
      and the H.G.W.J. Schweickerdt Herbarium (PRU), University of Pretoria. Biological
      samples from a group of 15 people exposed to HgCl(2) in herbaria and a non
      exposed control group of five people were studied. Additionally, plant samples
      from herbarium specimens treated and non-treated with HgCl(2) were analysed.
      Plant materials treated with HgCl(2) had persistent high concentrations of Hg in
      the range of 114-432 microg g(-1), whereas untreated materials were in the range
      of 0.20-0.45 microg g(-1). The HgCl(2)-treated plant specimens induced elevated
      concentrations of Hg into the herbarium rooms near storage cabinets, where up to
      1 microg m(-3) of Hg was measured in the air of both herbaria. However, no
      significant difference in mean Hg concentrations in hair was found between
      herbarium workers and members of the control group, 0.46 and 0.64 microg g(-1)
      respectively (p0.05, Student's t-test). For both groups, Hg concentrations were
      lower than that indicated by the World Health Organization [WHO] for non-exposed
      adults, namely 2 microg g(-1). The mean concentration of total Hg in urine from
      the mercury-exposed herbarium group, 2.28 microg g(-1) creatinine, was
      significantly higher than in the control group, 1.05 microg g(-1) of creatinine.
      For both populations, the concentrations of Hg in their urine were below the
      threshold Hg values set by the WHO, i.e., 5 microg g(-1) creatinine. We concluded
      that there was no strong response by individual herbarium staff from long-term
      exposure to Hg concentrations in the range of 0.28-1.1 microg m(-3).

PMID- 18817947
TI  - Detection of fungal development in a closed environment through the
      identification of specific VOC: demonstration of a specific VOC fingerprint for
      fungal development.
AB  - The occurrence of disease amongst the occupants of "mouldy" environments has been
      widely described in the literature. However, the detection of such moulds in
      closed environments remains difficult, particularly in the event of recent
      (before the first deterioration) or masked contamination (behind a material). In
      this context, the present study aimed to determine a specific chemical
      fingerprint for fungal development detectable in closed environments (dwellings,
      office, museum...). To achieve this, chemical emissions from sterile and
      artificially contaminated by moulds materials were analyzed and compared using a
      descriptive statistical method. Principal Component Analysis is thus chosen to
      analyze the results. PCA generated optimum and similar graphical representations
      of the scatterplot representing the data matrix. This statistical approach made
      it possible to identify an emission fingerprint without applying any
      preconception as to the type of emitted compound. Statistical analysis of the
      data then enabled confirmation of the impact of moulds on total VOC emissions.
      This emission of specific compounds resulted in obtaining a signature for the
      presence of fungal development in an environment, defined by specific ions. This
      analysis, and use of these ions applied to dwellings, made it possible to
      distinguish those with proven fungal development from those with no sign of mould
      or with a context favorable to fungal development, thus demonstrating that a
      chemical fingerprint specific to fungal development could be detected in indoor
      environments.

PMID- 18817948
TI  - Genes and environment - striking the fine balance between sophisticated
      biomonitoring and true functional environmental genomics.
AB  - This article provides an overview how the application of the gene profiling
      (mainly via microarray technology) can be used in different organisms to address
      issues of environmental importance. Only recently, environmental sciences,
      including ecotoxicology, and molecular biology have started to mutually fertilize
      each other. This conceptual blend has enabled the identification of the
      interaction between molecular events and whole animal and population responses.
      Likewise, striking the fine balance between biomonitoring and functional
      environmental genomics will allow legislative and administrative measures to be
      based on a more robust platform. The application of DNA microarrays to
      ecotoxicogenomics links ecotoxicological effects of exposure with expression
      profiles of several thousand genes. The gene expression profiles are altered
      during toxicity, as either a direct or indirect result of toxicant exposure and
      the comparison of numerous specific expression profiles facilitates the
      differentiation between intoxication and true responses to environmental
      stressors. Furthermore, the application of microarrays provides the means to
      identify complex pathways and strategies that an exposed organism applies in
      response to environmental stressors. This review will present evidence that the
      widespread phenomenon of hormesis has a genetic basis that goes beyond an
      adaptive response. Some more practical advantages emerge: the toxicological
      assessment of complex mixtures, such as effluents or sediments, as well as drugs
      seems feasible, especially when classical ecotoxicological tests have failed. The
      review of available information demonstrates the advantages of microarray
      application to environmental issues spanning from bacteria, over algae and
      spermatophytes, to invertebrates (nematode Caenorhabditis elegans, crustacea
      Daphnia spp., earthworms), and various fish species. Microarrays have also
      highlighted why populations of a given species respond differently to similar
      contaminations. Furthermore, this review points at inherent limits of microarrays
      which may not yet have been properly addressed, namely epigenetics, which may
      explain heritable variation observed in natural population that cannot be
      explained by differences in the DNA sequence. Finally, the review will address
      promising future molecular biological developments which may supersede the
      microarray technique.

PMID- 18817949
TI  - Development of agro-environmental scenarios to support pesticide risk assessment
      in Europe.
AB  - This paper describes work carried out within the EU-funded FOOTPRINT project to
      characterize the diversity of European agricultural and environmental conditions
      with respect to parameters which most influence the environmental fate of
      pesticides. Pan-European datasets for soils, climate, land cover and cropping
      were intersected, using GIS, to identify the full range of unique combinations of
      climate, soil and crop types which characterize European agriculture. The
      resulting FOOTPRINT European agro-environmental dataset constitutes a large
      number of polygons (approximately 1,700,000) with attribute data files for i)
      area fractions of annual crops related to each arable-type polygon (as an
      indicator of its probability of occurrence); and, ii) area fractions of each soil
      type in each polygon (as an indicator of its probability of occurrence). A total
      of 25,044 unique combinations of climate zones, agricultural land cover classes,
      administrative units and soil map units were identified. The same soil/crop
      combinations occur in many polygons which have the same climate while the
      fractions of the soils and arable crops are different. The number of unique
      combinations of climate, soil and agricultural land cover class is therefore only
      7961. 26-year daily meteorological data, soil profile characteristics and crop
      management features were associated with each unique combination. The agro
      environmental scenarios developed can be used to underpin the parameterization of
      environmental fate models for pesticides and should also have relevance for other
      agricultural pollutants. The implications for the improvement and further
      development of risk assessment procedures for pesticides are discussed.

PMID- 18817950
TI  - Sulphur leaching from headwater catchments in an eroded peatland, South Pennines,
      U.K.
AB  - A detailed investigation into sulphur leaching in peatland headwater catchments
      in the South Pennines, UK shows that, despite significant reductions in sulphur
      emissions, sulphur remains a key acidifier. This sulphur can be considered as
      legacy atmospheric pollution, stored within the peat by processes of
      dissimilatory sulphate reduction and now being leached into the region's surface
      waters. Persistently lower water tables at gully edge locations define a thick
      erosional acrotelm that is vulnerable to aeration, oxidation and flushing
      throughout the year, and not solely confined to periods of drought. Stream
      discharge behaves as a two-end member system, whereby pre-event water, rich in
      DOC and sulphate, is diluted by event water as a result of event water flowing
      through fast flow pathways such as macropores and overland flow. A rapid increase
      in water table elevation during the storm and a decrease in elevation after the
      storm indicate that event water has infiltrated the peat and has then been
      released into the stream. Streamwaters in peat dominated upland catchments with
      high densities of gullying have high concentrations of sulphate and low
      concentrations of DOC, whereas the reverse is true for those catchments with low
      densities of gullying. This is consistent with the concept that high
      concentrations of sulphate can suppress the solubility of DOC. A significant
      store of sulphate exists within South Pennine peats, and continued gully erosion
      will enhance sulphur leaching meaning that the timescale involved for any
      depletion is uncertain. It is therefore important that models predicting recovery
      from acidification in these upland systems include an understanding of how this
      stored sulphur is being leached, especially with respect to gully erosion,
      climate change and reduced precipitation.

PMID- 18817951
TI  - Association of periprocedural neurological deficit in carotid stenting with
      increased anticardiolipin antibodies.
AB  - INTRODUCTION: Carotid stenting (CS) has become a therapeutic alternative to
      endarterectomy in selected patients. Periinterventional plaque thromboembolism
      leading to neurological ischemic events remain the major risk of the procedure.
      We prospectively studied the potential role of thrombophilic conditions including
      anticardiolipin antibodies (ACA, IgG and IgM isotype), lupus anticoagulants,
      activated protein C resistance, antithrombin, and protein C and S. MATERIAL AND
      METHODS: The study was approved by the local ethics committee, and written
      informed consent was obtained from all patients. In total, 236 consecutive
      patients were included (158 men, 78 woman; median age 73 years). Prothrombotic
      markers were quantitated on the day of admission. Periprocedural neurological
      deficits (PND) occurring within 48 hours of the intervention were recorded and
      classified by an independent neurologist as transient ischemic attack, minor or
      major stroke. Uni- and multivariable logistic regression analysis were performed
      to test for the influence of thrombophilic conditions, demographic factors and
      lesion characteristics on PND. RESULTS: Neurologic complications occurred in 18
      interventions (7.6%). In 4 (36.4%; 3 minor, 1major stroke) out of 11 patients
      with elevated IgG-ACA neurological events were observed as compared to 14 (6.2%;
      6 TIA, 5 minor stroke, 3 major stroke) out of 225 patients with normal IgG-ACA
      levels. In multivariable analysis, two variables were independently associated
      with PND: elevated IgG-ACA (OR 6.09, 95% CI 1.49-25.88; P=0.012) and lesion
      length >10 mm (OR 4.36, 95% CI 1.19 to 16.01; P=0.027). CONCLUSIONS: A
      thrombophilic condition due to elevation of anticardiolipin antibodies increases
      the risk of periinterventional neurological complications during CS.

PMID- 18817952
TI  - Intraindividual thrombin generation measurement variability in healthy adults
      over a one year period.

PMID- 18817953
TI  - Insights from the 7th Southwest Symposium on Thrombosis and Hemostasis.

PMID- 18817954
TI  - Determining the course of the dorsal nerve of the clitoris.
AB  - OBJECTIVES: To describe the course and variation of the dorsal nerve of the
      clitoris (DNC) to better define its anatomy in the human adult before embarking
      on therapeutic strategies in this region of the body and as an aid to surgeons to
      help avoid iatrogenic injury to the DNC during vaginal surgical procedures.
      METHODS: Six human female cadavers of variable body weights were sectioned. A
      vertical midline incision from the base of the clitoris extending toward the
      direction of the umbilicus was made. The DNC was identified by dissecting out the
      fascia, fat, and muscles around it. The anatomy of the nerve was noted
      bilaterally. RESULTS: Distally, the DNC pierced the perineal membrane lateral to
      the external urethral meatus. It traversed along the bulbospongiosus muscle
      before traversing posterior to the crura. The DNC reappeared, hooking over the
      crura to lie on the anterolateral surface of the body of the clitoris, before
      dividing into 2 cords and terminating short of the tip of the glans clitoris.
      CONCLUSIONS: The results of this study have demonstrated the unique anatomy of
      the distal part of the DNC. Knowledge of the anatomy of the DNC, which was
      consistent for all the cadavers, is important so that surgeons can avoid
      potential iatrogenic injuries to this structure.

PMID- 18817955
TI  - Effect of naftopidil on nocturia after failure of tamsulosin.
AB  - OBJECTIVES: The clinical usefulness of naftopidil was evaluated in 122 patients
      with benign prostatic hyperplasia for urinary tract symptoms and signs, focused
      in particular on nocturia. METHODS: A total of 122 patients with BPH whose
      symptoms did not improve after 6 weeks of tamsulosin administration were
      enrolled. After the treatment was followed by a washout period with placebo,
      patients were prescribed 75 mg of naftopidil to be taken after dinner for 6
      weeks, and the efficacy was re-evaluated. All the drugs used were unidentified,
      and attention was given to not have the patients recognize the change in the drug
      given. The primary purpose of this study was the improvement of nocturia in
      patients with a poor response to tamsulosin. The clinical efficacy of naftopidil
      was defined as significant improvement in International Prostate Symptom Score,
      quality-of-life index, and maximal urinary flow rate. RESULTS: After 6 weeks of
      naftopidil administration, significant improvements in daytime and nighttime
      frequency, International Prostate Symptom Score, quality-of-life index, maximal
      flow rate, average flow rate, and bladder compliance were examined. On the
      International Prostate Symptom Score questionnaire, improvement in the sensation
      of the bladder not emptying and a reduction in nighttime frequency stood out.
      Moreover, detrusor overactivity was observed in 40 patients before the start of
      treatment and was eliminated in 31. The effective rate of this study was 69.7%
      (85/122). CONCLUSIONS: Naftopidil has novel effects in patients with BPH whose
      main complaints are storage and voiding symptoms, especially that of nocturia of
      >or=3 times, as well as in patients with a low compliance bladder and detrusor
      overactivity, who did not respond to tamsulosin.

PMID- 18817956
TI  - Bilateral extravesical ureteral reimplantation in toilet-trained children: short
      stay procedure without urinary retention.
AB  - OBJECTIVES: We have previously reported on the ability of toilet-trained children
      to undergo bilateral extravesical ureteral reimplantation with a 1-day
      hospitalization and without urinary retention using a critical pathway and
      modification of the surgical technique. The objective of this study was to
      determine whether additional refinement of the critical pathway and surgical
      technique could continue to result in 1-day hospitalization and possibly an
      outpatient procedure, without urinary retention, in toilet-trained children.
      METHODS: We evaluated all toilet-trained children undergoing bilateral
      extravesical ureteroneocystostomy, with a critical pathway for preoperative
      education, operative management, and postoperative care. A modified technique was
      used that limits ureteral dissection, ureteral mobilization, and detrusor
      dissection to as distally as possible such that a 5:1 ratio of tunnel length to
      ureteral diameter can be accomplished. Patients followed a strict postoperative
      critical pathway, and parents received extensive preoperative and postoperative
      education. A child was required to fulfill 5 strict criteria to be discharged
      from the hospital. RESULTS: A total of 84 patients underwent bilateral
      extravesical ureteral reimplantation. Of the 84 patients, 64 were girls and 20
      were boys. The age range was 1.9-12.8 years (mean 4.6). The first 78 patients
      were discharged on the first postoperative day as planned. The next 6 patients in
      this series were discharged the same day as surgery as planned, using the
      modification of the critical pathway. All patients were able to spontaneously
      void postoperatively without any instances of acute or chronic urinary retention,
      acute urinary tract infection, or rehospitalization. CONCLUSIONS: The results of
      this study further support our initial findings that bilateral extravesical
      ureteral reimplantation can be performed in toilet-trained children after a 1-day
      hospitalization without postoperative urinary retention. In the present study,
      this was also accomplished as an outpatient procedure.

PMID- 18817957
TI  - CounterPoint: second malignancies after radiotherapy for prostate cancer: keeping
      perspective.

PMID- 18817958
TI  - Testicular catch-up growth after varicocelectomy: does surgical technique make a
      difference?
AB  - OBJECTIVES: Catch-up growth of the affected testis in adolescents after
      varicocele repair has been well documented. Many investigators have found
      evidence that testicular hypotrophy related to varicocele can be reversed by
      early intervention. The aim of this study was to analyze the testicular catch-up
      growth rate in pediatric patients, correlating it with patient age at surgery,
      varicocele size, procedures used, and semen quality. METHODS: Between March 1990
      and September 2006, a total of 465 varicocelectomies were performed at our
      department. We evaluated the mean testicular volume before and after
      varicocelectomy in patients aged 9-14 years. Two procedures were used:
      laparoscopic artery-preserving varicocelectomy (group 1) and open inguinal
      microscopic artery-preserving varicocelectomy with a venous-venous bypass (group
      2). The testicular volume was measured before and after surgery using
      ultrasonography, and the mean testicular catch-up growth was recorded. RESULTS:
      Although the overall catch-up growth rate for both groups was 80%, after 18
      months, only 45% of patients in group 1 and 34% of patients in group 2 had equal
      bilateral testicular volume. None of these procedures showed a statistically
      significant correlation with age at surgery, varicocele size, or catch-up rate.
      The semen analysis results did not show statistically significant differences
      between the 2 groups. CONCLUSIONS: Although 80% of patients demonstrated
      testicular catch-up, with a different distribution depending on the procedure
      type used but without statistically significant differences, only 32% of patients
      had complete and real testicular volume catch-up.

PMID- 18817959
TI  - Pediatric robotic-assisted laparoscopic diverticulectomy.
AB  - Congenital bladder diverticula are rare anomalies of the bladder. Patients
      present with infection, hematuria, and/or urinary obstruction. We report on the
      case of a 12-year-old boy who developed gross hematuria and recurrent infection
      owing to a 12-cm bladder diverticulum. Robotic-assisted laparoscopic
      diverticulectomy was performed. We describe the first reported robotic-assisted
      laparoscopic diverticulectomy in a pediatric patient.

PMID- 18817960
TI  - A learning package for medical students in a busy urology department: design,
      implementation, and evaluation.
AB  - OBJECTIVES: The need for innovation in the delivery of quality teaching and
      learning for undergraduates in urology is driven by a number of factors. An
      increasing proportion of care is delivered in ambulatory settings, hospital
      inpatients are increasingly unwell, and the National Health Service staff must
      find a balance in their dual roles as healthcare providers and clinical teachers.
      We describe the design, implementation, and evaluation of an innovative learning
      package for undergraduate medical students in urology. This consisted of a
      simulated urology outpatient clinic to prepare students for learning in the
      outpatient environment and an on-line self- and peer-assessed learning exercise
      to provide students with the necessary clinical knowledge of the core problems in
      urology and to encourage reflection. METHODS: Action research principles were
      used to design, deliver, and evaluate a model for teaching and learning in the
      outpatient setting. Fourth-year medical students at the start of a 1-week
      clinical teaching block were given the opportunity to participate in a simulated
      urology outpatient clinic. On-line support material was designed around 2 core
      clinical problems in urology. The evaluations were gathered using an anonymous on
      line questionnaire and a pre- and postcourse test of knowledge for a sample
      group. RESULTS: Of the students who responded, 100% found the on-line material
      helpful for learning about the core clinical problems. The results demonstrated a
      12% improvement in scores in a knowledge test at 1 week and 18% at 1 month after
      the teaching block compared with the control group from the previous academic
      year for which the mean improvement was 7% at 1 week and 8% at 1 month after the
      teaching program. CONCLUSIONS: The evaluation results demonstrated a positive
      effect on learning without compromise to the service provided to patients. This
      could be developed as a model for teaching and learning urology or other
      specialties.

PMID- 18817961
TI  - Effects of serum PSA on efficacy of tolterodine extended release with or without
      tamsulosin in men with LUTS, including OAB.
AB  - OBJECTIVES: To evaluate the efficacy of tolterodine extended release (ER),
      tamsulosin, and tolterodine ER plus tamsulosin in men with symptoms of overactive
      bladder and benign prostatic hyperplasia stratified by prostate-specific antigen
      (PSA) level. METHODS: We performed a post hoc analysis of data from men >or=40
      years old with frequency and urgency (with or without urge urinary incontinence),
      postvoid residual urine volume <200 mL, maximal urinary flow rate >5 mL/s,
      International Prostate Symptom Score (IPSS) of >or=12, and quality-of-life score
      of >or=3. They had been randomized to placebo, tolterodine ER (4 mg), tamsulosin
      (0.4 mg), or tolterodine ER plus tamsulosin for 12 weeks. The men were stratified
      by the median baseline PSA level (>or=1.3 vs <1.3 ng/mL). Assessments included
      changes in bladder diary variables and IPSSs. The men rated the urgency level of
      each micturition, and the frequency-urgency sum was defined as the total of these
      ratings. RESULTS: The PSA level correlated significantly with prostate size. Men
      with a PSA level of >or=1.3 ng/mL receiving tolterodine ER plus tamsulosin showed
      significantly greater improvements in 24-hour frequency, daytime frequency, the
      frequency-urgency sum, total IPSS, and IPSS storage score compared with those
      receiving placebo. Tamsulosin significantly improved the IPSS voiding scores, but
      tolterodine ER was ineffective. In men with a PSA level <1.3 ng/mL, tolterodine
      ER alone and tolterodine ER plus tamsulosin significantly improved the 24-hour
      frequency, daytime frequency, frequency-urgency sum, and IPSS storage scores
      compared with those receiving placebo; tamsulosin alone was ineffective. No
      significant changes were found in the postvoid residual urine volume or maximal
      urinary flow rate in any group, and the acute urinary retention rates were low.
      CONCLUSIONS: The results of our study have shown that tolterodine ER was
      efficacious in men with lower urinary tract symptoms, including overactive
      bladder, who had lower PSA levels (<1.3 ng/mL).

PMID- 18817962
TI  - Prevalence and epidemiologic characteristics of lower urinary tract stones in
      Japan.
AB  - OBJECTIVES: To analyze the changes in the annual incidence and epidemiologic
      details of lower urinary tract stones in Japan, a nationwide survey of
      urolithiasis was performed. METHODS: Data were obtained from all patients who had
      been diagnosed by urologists in 2005 as having lower urinary tract stones,
      including both first and recurrent stones. The data were separately enumerated
      according to hospital size, irrespective of admission and treatment. The study
      included all hospitals approved by the Japanese Board of Urology and thus covered
      nearly all urologists practicing in Japan. The estimated annual incidence
      according to sex, age, and stone composition was compared with other nationwide
      surveys taken from 1965 to 1995. RESULTS: The incidence of lower urinary tract
      stones in Japan has steadily increased from 4.7/100,000 in 1965 to 9.1/100,000 in
      2005. However, the age-standardized annual incidence of lower urinary tract
      stones in Japan decreased slightly from 5.5/100,000 in 1965 to 5.4/100,000 in
      2005. The incidence of stones containing calcium has significantly increased from
      50.7% to 72.0% among men and the incidence of infection-related stones has
      decreased significantly from 26.2% to 10.1%. The ratios of uric acid calculi in
      men and of infection-related stones in women increased with age. CONCLUSIONS: The
      increased incidence of lower urinary tract stones is in slight contrast to the
      sudden increase in the incidence of upper urinary tract stones, which might be
      associated with the aging of the Japanese population.

PMID- 18817963
TI  - The advantages of LDL (low density lipoproteins) in the cryopreservation of
      canine semen.
AB  - A medium containing LDL (Low Density Lipoproteins, the cryoprotective component
      of chicken egg yolk) was compared with egg yolk for the preservation canine
      spermatozoa during the freeze-thaw process. Twenty sperm samples taken from 10
      dogs were frozen in liquid nitrogen at -196 degrees C in seven different media:
      one control medium containing 20% egg yolk, and six test media containing 4%, 5%,
      6%, 7%, 8%, and 10% LDL, respectively. Following thawing, sperm motility was
      assessed using a Hamilton-Thorne Sperm Analyser equipped with the CEROS 12
      software. The percentage of motile spermatozoa was 55.3% in the 6% LDL medium
      (optimal concentration) compared with 27.7% in the egg yolk based medium
      (p<0.05). In comparison with the egg-yolk medium, the LDL medium also resulted in
      an improved preservation of spermatozoa during the freezing process (p<0.05) in
      terms of acrosomal integrity (FITC-PSA test), flagellar plasma membrane integrity
      (HOS test), and DNA integrity (Acridine Orange test). In addition, six Beagle
      bitches were inseminated twice, via the intra-uterine route, at an interval of
      24h; 200x10(6) spermatozoa that had been previously frozen in the 6% LDL medium
      were used per insemination. All of the bitches became pregnant (gestation rate of
      100%). In conclusion, the 6% LDL medium provides improved protection of the
      spermatozoa during the freeze-thaw process and a marked improvement in the
      motility parameters of canine spermatozoa in comparison with the control medium
      containing egg yolk alone. Finally, the use of LDL as a cryoprotectant for canine
      semen does not interfere with fertility.

PMID- 18817964
TI  - Cloning and characterization of a novel oocyte-specific gene zorg in zebrafish.
AB  - Genes specifically expressed in oocytes are important for the development of both
      germ cells and embryos. Using the digital differential display program from the
      NCBI, we identified a novel EST sequence (no. DT881820) from zebrafish ovary
      libraries in the GenBank. The full-length cDNA of this transcript was obtained by
      performing 3'- and 5'-RACE and was confirmed by PCR and direct sequencing
      methods. The cDNA clone for this novel gene consisted of 894 base pairs and
      encoded a protein with 215 amino acids. Since this protein shared no significant
      homology with any other known proteins, we have named this gene zorg (zebrafish
      oogenesis related gene). Based on RT-PCR analysis, this gene was specially
      expressed in the ovary and was abundantly present at the blastula stage. However,
      the level of expression decreased significantly during the early gastrula
      periods. Based on whole-mount in situ hybridization studies, zorg transcripts
      were uniformly distributed in the cleavage stage through to the blastula stage.
      In addition, during early gastrulation, zorg transcripts appeared in the dorsal
      region, but became restricted to the primordial germ cells (PGC) in early
      somitogenesis and remained visible in PGC as they migrated towards the region of
      the gonad of embryos 24h post-fertilization. In situ hybridization of sectioned
      ovaries demonstrated that zorg mRNAs appeared in the cytoplasm of stage I and
      stage II oocytes and localized in the cortex of stage III and stage IV oocytes
      during oogenesis. We hypothesized that the protein expressed from the zebrafish
      zorg gene has roles in the formation of the female germ cells and in early
      embryonic development in zebrafish.

PMID- 18817965
TI  - Comparison of different osmolalities and egg-yolk composition in processing media
      for the cryopreservation of red wolf (Canis rufus) sperm.
AB  - Successful cryopreservation of sperm and the maintenance of a sperm-based genome
      resource bank have been identified as priorities for the recovery of the
      endangered red wolf (Canis rufus). The objectives were to improve sperm
      processing and to determine the relative timing of damage to red wolf sperm
      during freezing and thawing. Fresh ejaculates (n=37) from adult red wolves (n=15,
      aged 2-13 y) were collected via electroejaculation and subjected to cooling,
      freezing and thawing in four TRIS-egg-yolk extender treatments varying in
      osmolality ( approximately 305 mOsm versus approximately 350 mOsm) and egg-yolk
      composition (0.8 microm-filtered versus unfiltered). Ejaculates were evaluated
      for sperm percentage motility, forward progressive motion, and morphological
      characteristics immediately upon collection and following extension, cooling
      (prior to freezing) and thawing. Although no single treatment consistently
      produced superior results, sperm suspended in approximately 305 mOsm extenders
      exhibited slight losses in motility post-thawing (13 and 7%). Also, sperm
      suspended in approximately 350 mOsm extenders tended to have slower rates of
      decline in motility in vitro post-thawing than those stored in approximately 305
      mOsm extenders (P=0.55). Finally, extenders incorporating unfiltered egg yolk
      exhibited a slightly larger ratio of absent to partial acrosomes than did sperm
      frozen in extenders prepared with clarified egg yolk. For approximately 350 mOsm
      extenders, most motility loss occurred during the cooling rather than freezing
      and thawing. In conclusion, these data contribute to knowledge regarding
      cryopreservation of red wolf sperm.

PMID- 18817966
TI  - Effectiveness of exposure to longday followed by melatonin treatment on semen
      characteristics of Damascus male goats during breeding and non-breeding seasons.
AB  - Eight mature Damascus male goats were randomly divided into two equal groups. The
      first group served as control and the second group was used to study the effect
      of exposure to longday (16L/8D) followed by melatonin treatment
      (2mg/(animal/day)) on semen characteristics and blood hormonal levels during
      breeding and non-breeding seasons. During breeding season, longday exposure
      followed by melatonin treatments resulted in significant increases (P<0.01) in
      means of sperm motility, ejaculate volume, sperm concentration, total sperm
      output, total functional sperm fraction and blood testosterone concentration,
      while means of reaction time, dead sperm, abnormal sperm and blood
      triiodothyronine (T(3)) concentration were significantly decreased (P<0.01).
      During non-breeding season, longday exposure followed by melatonin treatment
      exhibited improvements in some reproductive parameters by reducing (P<0.05)
      reaction time and percentage of dead sperm (P<0.01) and increasing (P<0.05) total
      functional sperm fraction. Furthermore, longday exposure followed by melatonin
      treatment resulted in significant increases (P<0.01) in both of blood
      testosterone and T(3) concentrations. It is concluded that longday exposure
      followed by melatonin treatment successfully improve semen characteristics of
      Damascus male goats during breeding and non-breeding seasons. However, the
      beneficial effects were more pronounced during the breeding season.

PMID- 18817967
TI  - Temperature change in pulp cavity in vitro during the polymerization of
      provisional resins.
AB  - OBJECTIVES: To measure the temperature change in the pulp cavity of an extracted
      tooth during the polymerization of provisional resins within impression putty and
      polyethylene matrices. The effect of pre-cooling the putty matrix was also
      evaluated. METHODS: A freshly extracted premolar tooth had putty impressions
      recorded prior to crown preparation. Putty matrices were stored at room
      temperature, 4 and -12 degrees C prior to use. A thermocouple placed in the pulp
      chamber recorded the temperature change every 15s for a 10-min duration during
      polymerization of three resins using putty and clear polyethylene matrices. Five
      recordings were made with each material at each storage temperature. RESULTS:
      There is a temperature rise of 3.4-5.5 degrees C when the resins were autocured
      in a putty matrix. When the polyvinyl matrix was used the temperature rise
      increased to 4.0-8.2 degrees C (P<0.001). The temperature rise was reduced to
      zero when the putty had been pre-cooled in the fridge (P<0.001) and reduced
      further following pre-cooling in the freezer (P<0.001). SIGNIFICANCE: The use of
      a polyvinyl matrix allows higher pulp temperature rises to occur due to the
      exotherm from provisional resins. Lower temperatures were recorded when putty was
      used. The temperature rise could be eliminated when the putty was cooled at 4
      degrees C prior to reinsertion.

PMID- 18817968
TI  - Global epidemiology of injecting drug use and HIV among people who inject drugs:
      a systematic review.
AB  - BACKGROUND: Injecting drug use is an increasingly important cause of HIV
      transmission in most countries worldwide. Our aim was to determine the prevalence
      of injecting drug use among individuals aged 15-64 years, and of HIV among people
      who inject drugs. METHODS: We did a systematic search of peer-reviewed (Medline,
      EmBase, and PubMed/BioMed Central), internet, and grey literature databases; and
      data requests were made to UN agencies and international experts. 11 022
      documents were reviewed, graded, and catalogued by the Reference Group to the UN
      on HIV and Injecting Drug Use. FINDINGS: Injecting drug use was identified in 148
      countries; data for the extent of injecting drug use was absent for many
      countries in Africa, the Middle East, and Latin America. The presence of HIV
      infection among injectors had been reported in 120 of these countries. Prevalence
      estimates of injecting drug use could be ascertained for 61 countries, containing
      77% of the world's total population aged 15-64 years. Extrapolated estimates
      suggest that 15.9 million (range 11.0-21.2 million) people might inject drugs
      worldwide; the largest numbers of injectors were found in China, the USA, and
      Russia, where mid-estimates of HIV prevalence among injectors were 12%, 16%, and
      37%, respectively. HIV prevalence among injecting drug users was 20-40% in five
      countries and over 40% in nine. We estimate that, worldwide, about 3.0 million
      (range 0.8-6.6 million) people who inject drugs might be HIV positive.
      INTERPRETATION: The number of countries in which the injection of drugs has been
      reported has increased over the last decade. The high prevalence of HIV among
      many populations of injecting drug users represents a substantial global health
      challenge. However, existing data are far from adequate, in both quality and
      quantity, particularly in view of the increasing importance of injecting drug use
      as a mode of HIV transmission in many regions.

PMID- 18817969
TI  - Injecting drug use, HIV, and what to do about it.

PMID- 18817970
TI  - Nematode community dynamics over an annual production cycle in the central North
      Sea.
AB  - Nematode species composition, trophic structure and body size distributions were
      followed over an annual production cycle in the central North Sea; to test
      responses to temporally changing food quality and quantity in the sediment.
      Changes in the phytoplankton concentration in the water column were
      quantitatively reflected in the concentration of chlorophyll a and breakdown
      products in the sediment, with higher concentrations in spring and autumn
      following blooms, and lower concentrations in summer and winter. The taxonomic
      and trophic structure of nematode communities differed significantly among
      stations over relatively short distances, potentially masking some of the
      temporal dynamics. Spatio-temporal differences in nematode species composition
      were linked to changes in the quality and quantity of organic material reaching
      the seabed, reflecting a species-specific response to the nutritional quality of
      sedimenting organic material and the biochemical changes in the sediment
      associated with its decomposition. The size distributions of selected nematode
      species indicated that most species bred continuously throughout the sampling
      period, although one species, the epigrowth feeder Spilophorella paradoxa, had
      periods of increased growth following the deposition of the spring phytoplankton
      bloom. There was no consistent temporal relationship between the trophic
      composition of nematode communities and spring chlorophyll a or carbon
      sedimentation, most likely a result of the trophic plasticity of most feeding
      types and the capacity of the community to use both freshly sedimented material
      as well as the subsequent breakdown products and refractory organic matter.
      Community metrics implied that there were small responses to the seasonal
      production cycle, but these belied strong responses of a few species with life
      histories that allowed them to track the availability of suitable food resources.

PMID- 18817971
TI  - Synthesis, characterization, and in vivo diagnostic applications of hyaluronic
      acid immobilized gold nanoprobes.
AB  - Herein we describe a new class of multifunctional gold nanoprobes for ultra
      sensitive optical detection of reactive oxygen species (ROS) and hyaluronidase
      (HAdase). The nanoprobes were fabricated by end-immobilizing near-infrared
      fluorescence (NIRF) dye labeled hyaluronic acid (HA) onto the surface of gold
      nanoparticles (AuNPs). The nanoprobes effectively induced nanoparticle surface
      energy transfer (NSET) between NIRF dyes and AuNPs. When the surface immobilized
      HA was cleaved by ROS and HAdase, strong fluorescence recovery signals were
      attained with extreme sensitivity. In live animal models of rheumatoid arthritis
      (RA) and metastatic tumor, local arthritic inflammation and tumor sites were
      clearly identified upon systemic injection of the nanoprobes. These results
      suggest that the gold nanoprobes can be exploited not only as in vitro molecular
      and cellular imaging sensors for ROS and HAdase, but also as in vivo optical
      imaging agents for detection of local HA degrading diseases such as RA and tumor.

PMID- 18817972
TI  - Sustained complete molecular remission after imatinib discontinuation due to
      severe aplastic anemia.

PMID- 18817973
TI  - The Staff Attitude to Coercion Scale (SACS): reliability, validity and
      feasibility.
AB  - OBJECTIVES: Staff attitudes to the use of coercion are assumed to be a predictive
      factor for how much coercion is used in mental health care. The aim of this
      project has been to develop a questionnaire to measure staff attitudes to
      coercion. The development of the questionnaire is part of a broader project to
      investigate if staff attitudes to coercion influence how much coercion is
      actually used in mental health care. METHOD: A 15-item questionnaire has been
      developed through a process that included item constructing and sampling, a pilot
      study and testing reliability and validity. The questionnaire has been tested on
      a sample of 215 staff members from 15 acute and sub-acute psychiatric wards in
      Norway. Descriptive statistics and Cronbach Alpha were used to examine the
      psychometric properties of the items, and principal component analysis was used
      to analyse the dimensional structure. RESULTS: A model with three attitudes was
      found based on principal component analysis and clinical considerations. The
      three attitudes have been named: Coercion as offending (critical attitude) - the
      view of coercion as offensive towards patients; Coercion as care and security
      (pragmatic attitude) - the view of coercion as needed for care and security, and
      Coercion as treatment (positive attitude) - the view of coercion as a treatment
      intervention. CONCLUSION: A 15-item questionnaire to measure staff attitudes to
      coercion has been developed and named the Staff Attitude to Coercion Scale
      (SACS). The questionnaire has shown good reliability, validity and feasibility.

PMID- 18817974
TI  - A review of regulatory decisions for environmental protection: part I -
      challenges in the implementation of national soil policies.
AB  - Since many soil studies have already revealed the possible risks to human health
      and the environment arising from contaminated soils it is therefore crucial to
      preserve soil quality under current and future conditions. In the last three
      decades a number of countries already introduced national policies and practices
      for the management of contaminated sites, and in 2002, an EU Thematic Strategy
      for Soil Protection was proposed by the European Commission. In this paper we
      review and analyse several national contaminated land policy regimes already in
      place in order to assess common elements and to identify specific needs in the
      development of national soil policies. We propose a framework that combines the D
      P-S-I-R structure of policy evaluation with the Source-Pathway-Receptor approach
      to health risk assessment to support the development of effective country
      specific regulatory decisions for managing contaminated land in countries where
      these are yet to be implemented. The framework proposed allows decision makers to
      effectively use available information and to identify existing data gaps. As a
      result it is apparent that while there are technical aspects of site
      characterisation, risk assessment and remediation processes that could be
      commonly implemented at an EU level there are certain trans-scientific aspects
      that require political choices and need to be customized by EU Member States.

PMID- 18817975
TI  - Molecular cloning, expression and immunological characterisation of Pas n 1, the
      major allergen of Bahia grass Paspalum notatum pollen.
AB  - Bahia grass, Paspalum notatum, is a clinically important subtropical grass with a
      prolonged pollination season from spring to autumn. We aimed to clone and
      characterise the major Bahia grass pollen allergen, Pas n 1. Grass pollen
      allergic patients presenting to a tertiary hospital allergy clinic were tested
      for IgE reactivity with Bahia grass pollen extract by skin prick testing,
      ImmunoCAP, ELISA and immunoblotting. Using primers deduced from the N-terminal
      peptide sequence of a group 1 allergen of Bahia grass pollen extract separated by
      two-dimensional gel electrophoresis, the complete Pas n 1 cDNA was obtained by
      rapid amplification of cDNA ends and cloned. Biological relevance of recombinant
      Pas n 1 expressed in Escherichia coli was assessed by serum IgE reactivity and
      basophil activation. Twenty-nine of 34 (85%) consecutive patients presenting with
      grass pollen allergy were skin prick test positive to Bahia grass pollen. The Pas
      n 1 cDNA has sequence homology with the beta-expansin 1 glycoprotein family and
      is more closely related to the maize pollen group 1 allergen (85% identity) than
      to ryegrass Lol p 1 or Timothy grass Phl p 1 (64 and 66% identity, respectively).
      rPas n 1 reacted with serum IgE in 47 of 55 (85%) Bahia grass pollen-allergic
      patients, activated basophils and inhibited serum IgE reactivity with the 29 kDa
      band of Bahia grass pollen extract. In conclusion the cDNA for the major group 1
      allergen of the subtropical Bahia grass pollen, Pas n 1, was identified and
      cloned. rPas n 1 is immunologically active and is a valuable reagent for
      diagnosis and specific immunotherapy of grass pollen allergy.

PMID- 18817976
TI  - The community prevalence of depression in older Australians.
AB  - OBJECTIVE: To estimate the prevalence of depression among older adults in
      Australia. METHOD: All general practitioners in Australia's five most populous
      states who satisfied certain eligibility criteria (e.g., sufficient weekly
      working hours, sufficient numbers of elderly patients) were invited to
      participate. Those who consented were asked to identify all of their patients
      aged 60+ and invite them (either directly or via the study team) to complete a
      questionnaire. The questionnaire identified those who had experienced 'clinically
      significant depression' and those who had experienced a 'major depressive
      episode' in the past two weeks, via the Patient Health Questionnaire (PHQ-9).
      Consenting patients completed the questionnaire and returned it to the study team
      in a reply-paid envelope. RESULTS: In total, 22,251 patients returned
      questionnaires. Overall, the age-adjusted rate of clinically significant
      depression was 8.2% (95%CI=7.8%-8.6%), with the age-adjusted rates for males
      being 8.6% (95%CI=7.9%-9.2%) and for females being 7.9% (95%CI=7.4%-8.4%). The
      overall, male and female age-adjusted rates for a major depressive episode were
      1.8% (95%CI=1.6%-2.0%), 1.9% (95%CI=1.6%-2.2%) and 1.7% (95%CI=1.5%-2.0%),
      respectively. DISCUSSION: Our study suggests that depression among older people
      is a major public health problem. The above estimates provide guidance for
      efficient planning of services, and establish a baseline against which preventive
      and treatment interventions can be assessed. Armed with this information, we can
      progress efforts at reducing this major health problem and its consequences.

PMID- 18817977
TI  - Psychomotor functioning in chronic fatigue syndrome and major depressive
      disorder: a comparative study.
AB  - BACKGROUND: Studies comparing chronic fatigue syndrome (CFS) and major depressive
      disorder (MDD) reported similarities as well as differences between the two
      disorders. However, whereas psychomotor symptoms have been studied extensively in
      MDD, such research in CFS is more limited. Moreover, the few studies that
      compared cognitive and motor performance in MDD and CFS yielded inconsistent
      results. This study hence directly compares fine psychomotor functioning in both
      syndromes. METHODS: Thirty-eight patients diagnosed with CFS without a current
      major depressive episode (MDE), 32 MDD patients with a current MDE and 38 healthy
      controls performed two computerized copying tasks differing in complexity: a line
      copying task that mainly requires motor effort and a figure-copying task
      requiring additional cognitive efforts. All participants were female. A
      multivariate general linear model was used to compute group differences. RESULT:
      Overall, both patient groups performed more slowly than the controls. Compared to
      CFS patients, patients with MDD needed significantly more time to copy the single
      lines but no such between-group performance difference was observed for the
      figure reproductions. In this latter copying task, the increasing complexity of
      the figures resulted in prolonged reaction times for all three participant groups
      with the effect being larger and the magnitude similar for the two patient
      groups. LIMITATIONS: All patients were female and most were on psychotropic
      medication. CONCLUSIONS: Both the MDD and CFS patients tested demonstrated an
      overall fine motor slowing, with the motor component being more affected in the
      MDD patients than in the CFS patients while both patient groups showed similar
      cognitive impairments.

PMID- 18817978
TI  - Development and validation of the Combined Emotional and Affective Temperament
      Scale (CEATS): towards a brief self-rated instrument.
AB  - BACKGROUND: Temperament relates to both emotional dimensions and prevailing mood,
      but these different views are rarely integrated. Based on a model where
      temperament works as a system with activation, inhibition and control (inspired
      in Cloninger's and Rothbart's models), which produce the affective tone (inspired
      by Akiskal's and Kraepelin's model), we developed and validated the Combined
      Emotional and Affective Temperament Scale (CEATS). METHODS: 1007 subjects (28%
      males) from the general population and university students filled in the
      instrument either in the Internet or in a pen and paper version. The CEATS has an
      emotional section (dimensional only), an Affective section (both dimensional and
      categorical) and an evaluation of problems and benefits related to temperament.
      The data was analyzed with standard psychometric batteries and different sections
      were compared. RESULTS: In the emotional section, 4 factors with Eingenvalue >1
      explained 46% of the variation. These factors were interpreted as drive, control,
      disinhibition-fear and anger, had a normal distribution and had satisfactory
      Chronbach's alphas (0.70-0.82). Anger was particularly associated with problems
      and drive with benefits. In the Affective section, all 10 categorical affective
      temperaments were selected, being euthymic and hyperthymic the most prevalent (18
      23%), followed by cyclothymic and irritable (11-13%), anxious and depressive (8
      9%) and dysphoric, disinhibited, labile and apathetic temperaments (3-7%). The
      dimensional evaluation of affective temperaments showed 95% of the sample was
      able to ascribe to at least one affective temperament. Only the euthymic and
      hyperthymic temperaments were clearly associated with a favorable problem/benefit
      profile. The comparison between the emotional and affective sections revealed
      that each affective temperament had a particular emotional configuration.
      LIMITATIONS: Both computerized and pen and paper versions were used. The sample
      was not evaluated for psychiatric symptoms. Quantification of the dimensional
      assessment of affective temperament is limited. CONCLUSIONS: The CEATS is a brief
      and adequate instrument to evaluate emotional and affective aspects of
      temperament simultaneously.

PMID- 18817979
TI  - Human trophoblast cells express the immunomodulator progesterone-induced blocking
      factor.
AB  - Progesterone-induced blocking factor (PIBF) is an immunomoduatory factor with
      anti-abortive properties. In this study, we present evidence that PIBF is
      synthesized in the human placenta and determine its cellular source. Expression
      of PIBF was analysed with polyclonal rabbit anti-human PIBF antibodies against
      recombinant N-terminal 48kDa PIBF in first trimester and term placental tissues
      and in the choriocarcinoma cell line JAR by means of immunohistochemistry,
      confocal laser scanning microscopy of double immunofluorescence labelling, and
      Western blotting; RT-PCR was performed for analysis of PIBF mRNA in isolated
      trophoblast cells. PIBF protein is present in human first trimester and term
      placenta. Double immunofluorescence labelling localised PIBF to the extravillous
      cytotrophoblast. PIBF is also expressed heterogeneously by syncytiotrophoblast
      and part of the villous cytotrophoblast. Full-length PIBF mRNA encoded by exons 1
      18 is present in isolated first trimester and term villous trophoblast and in the
      choriocarcinoma cell line JAR. The corresponding 90kDa protein is expressed by
      JAR cells, first trimester and term villous trophoblast cells. In addition, these
      cells express PIBF proteins of 50 and 34kDa. Trophoblast is a source of PIBF; its
      tissue distribution suggests a role both in systemic and local (decidual)
      immunoregulation.

PMID- 18817980
TI  - Platelet serotonin uptake in drug-naive depressive patients before and after
      treatment with citalopram.
AB  - We investigated the kinetic parameters of serotonin (5-HT) uptake into platelets
      in a group of 26 drug-naive patients suffering from major depression before and
      after 3-7 weeks of treatment with citalopram. The degree of depression was rated
      using the Hamilton Depression Rating Scale (HDRS). The 5-HT uptake
      characteristics in untreated depressive patients were not significantly different
      from those of normal subjects. The apparent Michaelis constant (K(M)) was
      significantly increased, the apparent maximal velocity (V(max)) was not different
      from baseline, and the uptake efficiency (V(max)/K(M)) was significantly
      decreased after citalopram treatment. A significantly positive correlation
      between K(M) and V(max) was found in all groups. There was a significantly lower
      V(max) and V(max)/K(M) in the female compared with the male depressed patients
      before citalopram treatment; a hypothesis was supported that lowered 5-HT uptake
      may reflect a gender-linked vulnerability to a serotonin-related depression. A
      significant negative correlation between 5-HT uptake efficiency and the initial
      HDRS score suggests that platelet 5-HT uptake can be used as a marker of
      effective depressive disorder pharmacotherapy. The initial severity of depression
      was significantly negatively correlated with V(max), which supported a hypothesis
      that the initial severity of depressive disorder could be related to the lower
      V(max).

PMID- 18817981
TI  - Sex- and age-related increase in prevalence rates of death wishes and suicidal
      ideation in the community: results from the KORA-F3 Augsburg Study with 3,154 men
      and women, 35 to 84 years of age.
AB  - Among risk factors for suicide, suicidal ideation (SID) is of paramount
      importance. This study sought to determine sex- and age-related SID point
      prevalence rates in the general population. A population-based survey of 3154
      subjects, 35 to 84 years, conducted in 2004/05 in southern Germany, identified
      170 subjects (5.4%; 95% CI 4.6-6.2) suffering from SID within the last 14 days.
      Age-adjusted short-term period prevalence in women (6.0%, 95% CI 4.9.-7.2) was
      higher than in men (4.0%, 95% CI 3.1-5.1). Among 10-year age groups, sex-related
      differences were only significant in middle-aged subjects (55-64 years).
      Prevalence increased significantly with age, leading to a prevalence of >10% in
      the oldest age group (75-84 years). The population-based approach demonstrates a
      substantial proportion of subjects suffering from SID, particularly in older age
      groups.

PMID- 18817982
TI  - Molecular characterization of cytokine TWEAK and its receptor Fn14 in pig (Sus
      scrofa).
AB  - Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is a member of the
      tumor necrosis factor superfamily (TNFSF). The interaction of TWEAK with its
      receptor fibroblast growth factor-inducible 14 (Fn14) regulates multiple cellular
      responses, including stimulation of proliferation, migration, apoptosis,
      angiogenesis, and induction of proinflammatory cytokines. This paper reports for
      the first time the molecular cloning of porcine TWEAK and Fn14 by EST and RACE
      strategies. The full-length cDNA of porcine TWEAK is 1327bp, including an open
      reading frame (ORF) of 747bp. Its genomic DNA consists of seven exons and six
      introns and is approximately 10kb in size by computer-assisted analysis. Sequence
      similarity at the amino acid level between porcine TWEAK and human or mouse was
      95 and 92%, respectively. The full-length cDNA of porcine Fn14 contains 691bp, of
      which 390bp are the ORF. Sequence similarity at the amino acid level between
      porcine Fn14 and human, or mouse, or frog was 95, 93 and 64%, respectively. Real
      time quantitative PCR (Q-PCR) analysis revealed that both TWEAK and Fn14 are
      constitutively expressed in various tissues in pig. Our results suggest that the
      TWEAK-Fn14 pathway is evolutionarily highly conserved. It will be helpful for
      investigation on the biological role of the TWEAK/Fn14 system in this important
      animal model. Furthermore, it provides insight into the molecular evolution of
      the emerging TWEAK and Fn14 families.

PMID- 18817983
TI  - Molecular cloning, sequencing and characterization of channel catfish (Ictalurus
      punctatus, Rafinesque 1818) cathepsin S gene.
AB  - Cathepsin S is a lysosomal cysteine endopeptidase of the papain family. Our
      preliminary results showed the up-regulation of cathepsin S (CTSS) transcript
      during the early stage of Edwardsiella ictaluri infection, leading us to
      speculate that CTSS may play a role in infection. In this report, we identified,
      sequenced and characterized the channel catfish CTSS cDNA. Total RNA from tissues
      was isolated and cDNA libraries were constructed by the rapid amplification cDNA
      end (RACE) method. The gene-specific primers in conjunction with the RACE primers
      were used to PCR amplify 5'- and 3'-ends of the CTSS transcript. The complete
      channel catfish CTSS cDNA comprised 1530 nucleotides including a 96-nucleotide 5'
      untranslated region (UTR), a 990-nucleotide open reading frame and a 444
      nucleotide 3'-UTR. The open reading frame appears to encode a protein of 329
      amino-acid residues with calculated molecular mass of 36.7kDa and pI of 5.96. The
      degree of conservation of the channel catfish CTSS amino-acid sequence in
      comparison to other species ranged from 56.6 to 68.5%. These results provide
      important information for further exploring the roles of channel catfish CTSS in
      antigen processing.

PMID- 18817984
TI  - The effects of MPTP on the activation of microglia/astrocytes and
      cytokine/chemokine levels in different mice strains.
AB  - The effects of MPTP on two mouse strains with different MPTP sensitivities and
      immunological backgrounds were compared: MPTP-sensitive C57BL/6 mice (B6) with a
      propensity for Th1 and less MPTP-sensitive BALB/c mice (BALB) with a propensity
      for Th2. It was found that acute MPTP treatment induced behavioral dysfunction,
      activated microglia/astrocytes, and increased the levels of IL-10, IL-12(p40) IL
      13, IFN-gamma, and MCP-1 in CSF in B6, but not in BALB. This suggests that
      variances in immunological backgrounds might be a major contributing factor in
      sensitivity differences to MPTP.

PMID- 18817985
TI  - Anti-GM2 gangliosides IgM paraprotein induces neuromuscular block without
      neuromuscular damage.
AB  - We analyzed the effect on the mouse neuromuscular synapses of a human monoclonal
      IgM, which binds specifically to gangliosides with the common epitope [GalNAc
      beta 1-4Gal(3-2 alpha NeuAc)beta 1-]. We focused on the role of the complement.
      Evoked neurotransmission was partially blocked by IgM both acutely (1 h) and
      chronically (10 days). Transmission electron microscopy shows important nerve
      terminal growth and retraction remodelling though axonal injury can be ruled out.
      Synapses did not show mouse C5b-9 immunofluorescence and were only immunolabelled
      when human complement was added. Therefore, the IgM-induced synaptic changes
      occur without complement-mediated membrane attack.

PMID- 18817986
TI  - Steroid treatment of hearing loss in enlarged vestibular aqueduct anomaly.
AB  - OBJECTIVE: 1. Determine whether corticosteroid therapy improves hearing
      thresholds of patients with enlarged vestibular aqueduct (EVA) anomaly. 2.
      Determine sample size for a future prospective study. METHODS: Retrospective
      chart review hearing loss in EVA patients comparing patients treated with
      corticosteroids and untreated patients. RESULTS: Eighty percent (n=5) of patients
      treated with steroids for hearing loss demonstrated audiometric improvement,
      compared to 14.3% of patients (n=7) not treated. The pure tone average improved
      by 17.7dB in the steroid treated group. A prospective, placebo-controlled trial
      would need between 19 and 45 patients in each group, treatment versus no
      treatment, to achieve statistical significance. CONCLUSION: Patients with EVA who
      develop hearing loss have a high rate of hearing improvement when treated with
      corticosteroid therapy. The hearing improvement appears to be better than
      spontaneous recovery.

PMID- 18817987
TI  - Sulphurous water inhalations in the prophylaxis of recurrent upper respiratory
      tract infections.
AB  - OBJECTIVE: The aim of this study was to evaluate the efficacy and the effect of
      sulphurous thermal water inhalations in the treatment of the recurrent upper
      respiratory tract (RURT) infections in children. METHODS: A total of 100 children
      with RURT infections were included. All children underwent a 12-day course warm
      vapour inhalations. For the inhalations, we used sulphurous thermal water in the
      group A, while physiological solution in the group B. At the beginning, at the
      end and 3 months after start, all children underwent medical history, ENT
      examination, plasma levels of immunoglobulins class E, G, A, M (IgE, IgG, IgA,
      IgM), subjective assessment of symptoms (VAS), nasal mucociliar transport time
      (NMTT) determination, and evaluation of frequency, duration, severity and social
      impact of RURT episodes. RESULTS: Compared with group B, after the treatment and
      at the end of the study, in children treated with sulphurous thermal water, the
      serum concentration of IgE was significantly (p<0.05) lower (75.13+/-27.1mg/dl vs
      96.87+/-41.3mg/dl; 74.23+/-26.2mg/dl vs 98.24+/-42.7 mg/dl), IgA titers were
      higher (238.14+/-122.1mg/dl vs 218.62+/-115.8 mg/dl; 239.72+/-119.7 mg/dl vs
      210.46+/-107.3mg/dl), serum concentrations of IgG and IgM unchanged, VAS scores
      presented a significant (p<0.05) improvement (1.8+/-0.19 vs 6.8+/-0.54; 1.9+/
      0.21 vs 6.9+/-0.61), NMTT was normal (11.15+/-1.59 min vs 17.63+/-2.17; 11.25+/
      2.10 min vs 17.77+/-2.19 min) and frequency, duration, severity and social impact
      of RURT episodes were significantly (p<0.05) lower. CONCLUSIONS: Our findings
      indicate that, in addition to their known effects, the sulphurous water also have
      an immunomodulant activity that contributes to their therapeutic effects.

PMID- 18817988
TI  - Twenty years of audiology in a patient with Norrie disease.
AB  - OBJECTIVE: To describe disease progression and treatment outcomes over a 20-year
      period (ages 5-25) in a young man with Norrie disease (occuloacousticocerebral
      dysplasia), ND; OMIM #310600. Affected individuals are born blind and develop
      progressive sensory loss with onset in adolescence. This disease is X-linked and
      has been associated with mutations of the NDP gene (Xp11.4). METHODS: The patient
      was followed using repeated audiograms, as well as reports of educational
      progress and hearing aid use. The specific mutation was found by molecular
      analysis. RESULTS: The patient demonstrated progressive sensory loss with good
      preservation of word recognition. The loss was initially high frequency and
      asymmetric in adolescence and became more severe, more symmetric and affected
      practically all frequencies by the end of childhood. Educational progress was
      affected by the cognitive effects of the syndrome, and hearing aid use was very
      effective. CONCLUSIONS: A bilateral progressive sensory loss with good
      preservation of word recognition was documented in detail. The residual word
      recognition supported good use of hearing aids in this case.

PMID- 18817989
TI  - Influence of respiratory biofeedback associated to re-expansive ventilation
      patterns in individuals with functional mouth breathing.
AB  - OBJECTIVES: Assess the effect of re-expansive respiratory patterns associated to
      respiratory biofeedback (RBF) on pulmonary function, respiratory muscle strength
      and habits in individuals with functional mouth breathing (FMB). METHODS: Sixty
      children with FMB were divided into experimental and control groups. The
      experimental group was submitted to 15 sessions of re-expansive respiratory
      patterns associated to RBF (biofeedback pletsmovent; MICROHARD((R)) V1.0), which
      provided biofeedback of the thoracic and abdominal movements. The control group
      was submitted to 15 sessions using biofeedback alone. Spirometry, maximum static
      respiratory pressure measurements and questions regarding habits (answered by
      parents/guardians) were carried out before and after therapy. The Student's t
      test for paired data and non-parametric tests were employed for statistical
      analysis at a 5% level of significance. RESULTS: Significant changes were found
      in forced vital capacity, Tiffeneau index scores, maximum expiratory pressure,
      maximum inspiratory pressure and habits assessed in FMB with the use of RBF
      associated to the re-expansive patterns. No significant differences were found
      comparing the experimental and control groups. CONCLUSIONS: The results allow the
      conclusion that RBF associated to re-expansive patterns improves forced vital
      capacity, Tiffeneau index scores, respiratory muscle strength and habits in FMB
      and can therefore be used as a form of therapy for such individuals.

PMID- 18817990
TI  - Synaptic vesicle endocytosis: fast and slow modes of membrane retrieval.
AB  - Several modes of synaptic vesicle release, retrieval and recycling have been
      identified. In a well-established mode of exocytosis, termed 'full-collapse
      fusion', vesicles empty their neurotransmitter content fully into the synaptic
      cleft by flattening out and becoming part of the presynaptic membrane. The fused
      vesicle membrane is then reinternalized via a slow and clathrin-dependent mode of
      compensatory endocytosis that takes several seconds. A more fleeting mode of
      vesicle fusion, termed 'kiss-and-run' exocytosis or 'flicker-fusion', indicates
      that during synaptic transmission some vesicles are only briefly connected to the
      presynaptic membrane by a transient fusion pore. Finally, a mode that retrieves a
      large amount of membrane, equivalent to that of several fused vesicles, termed
      'bulk endocytosis', has been found after prolonged exocytosis. We are of the
      opinion that both fast and slow modes of endocytosis co-exist at central nervous
      system nerve terminals and that one mode can predominate depending on stimulus
      strength, temperature and synaptic maturation.

PMID- 18817991
TI  - Micro-rewiring as a substrate for learning.
AB  - How does the brain encode life experiences? Recent results derived from vital
      imaging, computational modeling, cellular physiology and systems neuroscience
      have pointed to local changes in synaptic connectivity as a powerful substrate,
      here termed micro-rewiring. To examine this hypothesis, I first review findings
      on micro-structural dynamics with focus on the extension and retraction of
      dendritic spines. Although these observations demonstrate a biological mechanism,
      they do not inform us of the specific changes in circuit configuration that might
      occur during learning. Here, computational models have made testable predictions
      for both the neuronal and circuit levels. Integrative approaches in the mammalian
      neocortex and the barn owl auditory localization pathway provide some of the
      first direct evidence in support of these 'synaptic-clustering' mechanisms. The
      implications of these data and the challenges for future research are discussed.

PMID- 18817992
TI  - Long-term effects of the antifouling booster biocide Irgarol 1051 on periphyton,
      plankton and ecosystem function in freshwater pond mesocosms.
AB  - Irgarol is a highly effective biocide used in antifouling coatings to prevent the
      growth of periphyton. Environmental concentrations of Irgarol in marine and
      freshwater have often exceeded the effect concentrations of autotrophic organisms
      tested in the laboratory and give reason for concern that natural periphyton
      communities may be endangered. A 150 days freshwater mesocosm study in 8 indoor
      ponds was conducted at nominal concentrations between 0.04 and 5 microgL(-1) in
      order to investigate the effects of Irgarol on periphyton and plankton. The
      results demonstrated that periphyton communities were strongly affected after
      single applications of 1 and 5 microgL(-1) Irgarol. For these concentrations no
      recovery was observed in the course of the study. For chlorophytes, the EC(50)
      (nominal, 135 days) was 0.34 microgL(-1). Phytoplankton also decreased in
      abundance directly after Irgarol application but recovered after a few weeks, as
      Irgarol concentrations rapidly decreased in the water body and nutrient levels
      increased due to lack of competition with periphyton and macrophytes. Zooplankton
      was indirectly affected by Irgarol. Principle response curve analysis revealed a
      species shift from macrophyte associated zooplankton species to free-swimming
      species. For species of cyclopoid copepods and ostracods the EC(50) was,
      respectively, 0.09 and 0.11 microgL(-1). The study simulated a best-case scenario
      since the mesocosms were dosed only once. Under field conditions, however,
      permanent exposure of organisms to Irgarol is more likely due to permanent
      leaching from painted ship hulls. Therefore, the effects presented in this study
      most likely underestimate the effects under natural conditions.

PMID- 18817993
TI  - Pioglitazone induces regression of coronary atherosclerotic plaques in patients
      with type 2 diabetes mellitus or impaired glucose tolerance: a randomized
      prospective study using intravascular ultrasound.
AB  - BACKGROUND: A large clinical trial clarified that pioglitazone reduces
      cardiovascular events in diabetic patients. However, effects of pioglitazone on
      structure of coronary atherosclerotic plaques have not been demonstrated. We
      examined whether pioglitazone reduces volumes of coronary atherosclerotic plaques
      using intravascular ultrasound (IVUS). METHODS: Twenty-six consecutive patients
      with type 2 diabetes mellitus (DM) or impaired glucose tolerance (IGT) undergoing
      percutaneous coronary intervention (PCI) were enrolled. Echolucent plaques
      without significant stenosis were selected in IVUS video images at non-PCI
      influenced coronary segments and volumetric analysis of the targeted plaques was
      performed. The patients were randomly assigned into 2 groups: pioglitazone group
      consisted of 13 patients taking pioglitazone 15 mg/day for initial 14 days after
      PCI and subsequent 30 mg/day during 6-month follow-up, and control group with 13
      patients as control. The plaque volumes and some parameters such as plasma lipid
      profiles and high-sensitive C-reacting protein (hs-CRP) levels were compared
      between baseline and the follow-up in those groups. RESULTS: In the pioglitazone
      group after 6 months, the plaque volume was significantly reduced (101.3+/-32.1
      to 94.6+/-33.6 mm(3), -7.2%; p=0.0023), plasma triglyceride was significantly
      decreased (- 14.9%) and high density lipoprotein cholesterol was substantially
      increased (+20.0%) without any significant change in low density lipoprotein
      cholesterol (LDL-C). Also, hs-CRP level tended to be decreased. However, no
      significant change in plaque volumes and those parameters was observed in the
      control group. CONCLUSIONS: Pioglitazone may induce regression of coronary
      atherosclerotic plaques without LDL-C reduction in patients with DM and IGT.

PMID- 18817994
TI  - Levosimendan for the treatment of acute severe heart failure: a meta-analysis of
      randomised controlled trials.
AB  - BACKGROUND: The objective of this study was to critically review the literature
      to evaluate whether levosimendan compared to standard therapy, in patients with
      acute severe heart failure, is associated with improved clinical outcomes.
      METHODS: Medline, EMBASE, and the Cochrane central register of clinical trials
      were searched. We also searched clinical trials registries, bibliographies of
      included studies and review articles and contacted the manufacturers of
      levosimendan to identify unpublished studies. Randomised clinical trials
      comparing levosimendan to standard therapy or placebo, in adult patients with
      acute severe heart failure, reporting at least one outcome of interest were
      included. Data were extracted regarding the characteristics, methodological
      quality and clinical outcomes, and combined using a fixed-effect meta-analysis.
      RESULTS: We identified 19 RCTs enrolling 3650 patients, only two studies
      fulfilled all of the validity criteria. There was a non-significant reduction in
      mortality with levosimendan compared with placebo (OR 0.83, 95%CI, 0.62-1.10,
      p=0.20). Levosimendan was associated with reduced mortality compared to
      dobutamine (OR 0.75, 95%CI, 0.61-0.92, p=0.005). Levosimendan was associated with
      improvements in haemodynamic parameters when compared to either placebo or
      dobutamine. CONCLUSIONS: Levosimendan improved haemodynamic parameters when
      compared with placebo, without showing evidence of survival benefit. Levosimendan
      improved both haemodynamics and survival when compared with dobutamine.

PMID- 18817995
TI  - A review of prevalences of paratuberculosis in farmed animals in Europe.
AB  - Prevalence estimates are used by decision makers such as policy makers and risk
      assessors to make choices related to certain diseases and infections.
      Paratuberculosis, caused by Mycobacterium avium subsp. paratuberculosis (MAP), is
      a chronic infection particularly resulting in economic losses among farmed
      ruminants. Therefore, this infection is of concern for many farming industry
      decision makers. As a result, multiple studies have been carried out to determine
      the within-herd and between-herd prevalence of MAP infections. The objective of
      the present study was to conduct a review and, if possible, compare animal and
      herd level prevalences of MAP among farmed animals in Europe. European data on
      prevalences of MAP in all farmed animal species were included from a review of
      literature. Information on target population and study design, tests used and
      apparent prevalences were recorded, and subsequently true prevalences were
      calculated when possible. A critical review of the included studies indicated
      that although a wide range of studies have been conducted, likely and comparable
      true prevalence estimates could rarely be calculated. Based on a few studies
      where the prevalences appeared to be plausible, it was concluded that prevalences
      of MAP would have to be guesstimates based on available data. The true prevalence
      among cattle appeared to be approximately 20% and was at least 3-5% in several
      countries. Between-herd prevalence guesstimates appeared to be >50%. No countries
      had published sufficient information to claim freedom from MAP or just a near
      zero prevalence of MAP infections. No within-flock prevalence estimates were
      available for goats and sheep. The between-flock prevalence guesstimates were
      >20%, based only on estimates from Switzerland and Spain. Major critical issues
      were identified in the majority of the studies, primarily due to lack of
      knowledge of the test accuracy of the diagnostic test used, or due to studies
      where the study population did not reflect the target population. Because most of
      the reported studies did not yield prevalence estimates which were comparable to
      other studies, there is a continuing need for well-designed studies of the
      prevalence of MAP infections.

PMID- 18817996
TI  - Protein expression by Listeria monocytogenes grown on a RTE-meat matrix.
AB  - Little is known about whether the growth of L. monocytogenes on a ready-to-eat
      (RTE) meat matrix has an impact on the bacterium's pathogenic capabilities. In
      this report, we examined protein expression by L. monocytogenes grown on RTE
      sliced turkey meat, using L. monocytogenes grown on brain-heart-infusion agar as
      a control. Total protein fractions of L. monocytogenes from both growth
      conditions were extracted and compared by two-dimensional gel electrophoresis.
      Seventy-seven proteins expressed by turkey meat-grown L. monocytogenes were
      identified by MALDI-TOF/TOF mass spectrometry analysis. The identified proteins
      include proteins known to be involved in virulence and stress adaptation such as
      ClpB, ClpC, ClpP, and surface antigen. This is the first report describing the
      proteome expressed by L. monocytogenes grown on a meat matrix. Our results
      suggest that certain proteins that are expressed by RTE meat-grown L.
      monocytogenes may contribute to the virulence of the bacterium.

PMID- 18817997
TI  - Sorafenib in advanced hepatocellular carcinoma - We have won a battle not the
      war.

PMID- 18817998
TI  - A prospective study of patient adherence to topical treatments: 95% of patients
      underdose.
AB  - BACKGROUND: Adherence is essential to a positive treatment outcome. Whether
      adequate doses of topically applied drugs are used among patients with
      dermatologic conditions has not been investigated adequately. OBJECTIVES: The
      objective of this prospective study was to determine to what extent first-time
      outpatients with dermatologic conditions apply the appropriate dosage of initial
      treatment with topically administered medication. METHODS: Consultations with
      first-time patients in the dermatologic outpatient clinic were observed. Patients
      receiving a prescription for a previously untried topically administered drug
      were eligible. The expected quantity of topical treatment to be used by each
      patient was calculated from the affected skin area to be treated. The affected
      area was estimated in numbers of palms of the hand, and an amount of 0.25 g of
      ointment or cream was chosen as sufficient treatment to cover the area of one
      palm. Two weeks after the consultation, a questionnaire with items regarding the
      size of the affected area, intentions to follow the treatment, and the applied
      dose the previous day was mailed to each patient. The questionnaires were
      personally collected from the patients' homes and at the same visit the patients'
      topical drug containers were weighed on a balance. Both patients and staff were
      blinded to the particular study purpose concerning adherence and dosing. RESULTS:
      In all, 17 patients were eligible. The majority received a prescription for
      topical corticosteroids, and the median area to be treated was 3 palms of the
      hand (interquartile range: 1.5-8). Two patients did not redeem their
      prescriptions. Only one patient used the expected dosage; in general median 35%
      (interquartile range: 22%-50%) of the expected individual dosages were used.
      LIMITATIONS: Only first-time patients who received a new and previously untried
      topical treatment were included, resulting in a small study size. CONCLUSIONS:
      Most first-time patients with dermatologic conditions underdose new topical
      treatments. Consequently, clinicians should always consider nonadherence when
      topical therapies fail.

PMID- 18817999
TI  - Indolent primary cutaneous B-cell lymphoma: experience using systemic rituximab.
AB  - BACKGROUND: Optimal treatment of indolent primary cutaneous B-cell lymphoma
      (CBCL), marginal zone lymphoma, and follicle center lymphoma, presenting as
      multiple lesions, has yet to be established. Rituximab is a chimeric monoclonal
      IgG1 antibody directed against the CD20 antigen of B cells. Clinical efficacy of
      systemic rituximab in CBCL has yet to be established. OBJECTIVE: We sought to
      assess the efficacy of systemic rituximab in the treatment of CBCL. METHODS: This
      was a retrospective study of 15 patients with indolent CBCL treated with
      intravenous rituximab (375 mg/m(2)) as a single agent. Variable maintenance
      regimen was used in a subset of patients. Responses were categorized as complete
      response, partial response, stable disease, or progressive disease. The efficacy
      end points included were objective response rate, time to response, time to
      progression, and duration of response. RESULTS: Ten patients with follicle center
      lymphoma and 5 with marginal zone lymphoma were included. The objective response
      rate was 87% (60% complete response, 27% partial response). All patients with
      follicle center lymphoma had a response with 80% achieving complete response. Of
      the patients with marginal zone lymphoma, 3 had a response, one stable disease,
      and one progressive disease. Median follow-up was 36 months. Median time to
      response, duration of response, and time to progression was 30 days, 24 months,
      and 24 months, respectively. LIMITATIONS: The study was limited by the small
      sample size and retrospective design. CONCLUSIONS: This study, although small,
      suggests that rituximab is a reasonable first-line treatment option for indolent
      CBCL with multiple lesions where local treatment is not effective or desirable.

PMID- 18818000
TI  - [Extrahepatic cholestasis secondary to Castleman's disease].
AB  - Castleman's disease is a rare lymphoproliferative disorder of unknown etiology
      with different clinical manifestations. A 76-year-old man presented with pruritus
      and jaundice, a cholestasis and an increase of acute phase reactants.
      Peroperative investigations evidenced a 3-cm lymphadenopathy that compressed the
      biliary duct. Diagnosis of multicentric Castleman's disease was confirmed by the
      histologic examination of the lymphadenopathy. HIV testing was negative.
      Corticosteroid therapy was started and partially controlled the disease.

PMID- 18818001
TI  - [A rare splenic lesion, the splenoma or splenic hamartoma].
AB  - We report a new case of splenoma in a previously healthy adult. A 52-year-old man
      was admitted for a splenomegaly with thrombocytopenia. The computed tomographic
      scan showed a tumor which measured 56 mm in diameter. A splenectomy was
      performed. Histologic examination of the splenectomy specimen revealed a
      splenoma. Splenoma or splenic hamartoma is a rare primary splenic tumor most
      often incidentally discovered, radiologically. It can also meet in a particular
      pathological context, evoking more a coexistence rather than an association or a
      complication, underlying the role of the pathologist in its diagnosis.

PMID- 18818002
TI  - [Assessment of myocardial perfusion in systemic lupus erythematosus].
AB  - INTRODUCTION: Cardiovascular disease is a major cause of morbidity and mortality
      in patients with systemic lupus erythematosus (SLE). Necropsy studies found a
      high incidence of myocardial and coronary injuries while clinical manifestations
      were observed in less than 10%. The purpose of this study was to evaluate
      myocardial perfusion in SLE patients. PATIENTS AND METHODS: The study was carried
      out in 153 patients with a definite diagnosis of SLE according to the revised
      criteria of the American College of Rheumatology. Ninety-four (61.4%) underwent
      99mTc-tetrofosmine SPECT analysis at rest and after stress. RESULTS: The average
      disease duration was 11 years. Ninety-four patients (93 women and one man) with a
      mean age 37 years were assessed. Twelve had a past history of vascular event: six
      stroke, four angina pectoris and two myocardial infarctions. Cardiovascular risk
      factor included: high blood pressure (35.2%), dyslipidemia (62.3%), moderate
      hyperhomocysteinemia (55%), BMI greater than 25 (40%).The cumulative prednisone
      dose per patient was 45.5g. Myocardial perfusion stress scanning showed abnormal
      perfusion in 21 patients (22.3%). Among these, eight underwent coronary
      angiography which was normal in seven cases. One patient had a right coronary
      stenosis. Perfusion abnormalities were correlated with stroke (p<0.01) and
      coronary events (p<0.02). CONCLUSION: Myocardial perfusion scintigraphy can be a
      useful noninvasive method to identify subclinical myocardial involvement in
      systemic lupus erythematosus and patients at risk of later events.

PMID- 18818003
TI  - [Recurrent acute pancreatitis revealing a hydatid cyst of the pancreas].
AB  - The authors report a case of hydatid cyst of the pancreas in a 29-year-old man.
      Biology and computed tomography contributed to the preoperative diagnosis. The
      intervention consisted in a left pancreatectomy with spleen ablation. In the
      light of this case and the literature review, the authors discuss diagnostic
      issues raised by hydatid cyst of the pancreas.

PMID- 18818004
TI  - [Recurrent inflammatory myofibroblastic tumor with renal, retroperitoneal and
      lymph node involvement].
AB  - Inflammatory myofibroblastic tumors are uncommon and benign tumors with unknown
      aetiology. First reported in the lungs, the inflammatory myofibroblastic tumors
      have been observed in other locations, especially in the abdomen and the pelvis.
      We report a 14-year-old adolescent female, who presented sequentially an
      inflammatory pseudotumor of lymph node, the left kidney and the retroperitoneum.
      Extrapulmonary inflammatory myofibroblastic tumors are mesenchymal solid tumors.
      They are frequently circumscribed and confined to a single organ. The recurrence
      of some inflammatory myofibroblastic tumors and their expression of chromosomal
      abnormalities found in some types of lymphoma suggest that some of these lesions
      constitute a true neoplastic process.

PMID- 18818005
TI  - Assessing deposition levels of 55Fe, 60Co and 63Ni in the Ignalina NPP
      environment.
AB  - Two RBMK-1500 reactor units operated in Lithuania in the 1987-2004 period (one of
      them was stopped for decommissioning in 2004). This study presents a preliminary
      investigation of surface deposition density levels of (55)Fe and (63)Ni in moss
      samples collected in the close vicinity of the Ignalina NPP. Non-destructive
      analysis by the HPGe gamma-spectrometry was followed by radiochemical separation.
      Radiochemical analysis was based on anion-exchange and extraction chromatography.
      (55)Fe and (63)Ni activities were measured by liquid scintillation counting
      (LSC). The results indicate that the deposition values of (55)Fe are generally
      higher than those of (60)Co and (63)Ni.

PMID- 18818006
TI  - Dentoalveolar fracture of the posterior maxilla.

PMID- 18818007
TI  - Temporal dynamics of awareness for facial identity revealed with ERP.
AB  - In this study, we investigated the scalp recorded event-related potential (ERP)
      responses related to visual awareness. A backward masking procedure was performed
      while high-density EEG recordings were carried out. Subjects were asked to detect
      a familiar face, presented at durations that varied parametrically between 16 and
      266 ms. ERPs were computed and awareness was assessed using a sensitivity measure
      from signal detection theory (d'). Modifications in the electrical scalp
      topographies were found to reflect visual awareness of the stimulus. In
      particular, an early map topography was found to emerge progressively around 230
      ms, showing a pattern of increase similar to the measure of visual awareness.
      This was followed by an increase in duration of a second, P300-like map. Source
      localisation for the early awareness-related topography revealed the activation
      of a distributed network of brain areas including frontal and temporo-occipital
      regions. Our results suggest that conscious experience emerges in parallel with
      the activation of a specific neural network that occurs in a time window
      beginning from about 200 ms.

PMID- 18818008
TI  - Monitoring acid-demineralization of human dentine by electrochemical impedance
      spectroscopy (EIS).
AB  - OBJECTIVE: The purpose of this study was to monitor in situ acid-induced
      demineralization of dentine by using electrochemical impedance spectroscopy (EIS)
      and correlate the EIS findings with changes in the chemical composition and
      ultrastructure of dentine. METHOD: EIS was used to monitor the process of
      demineralization of dentine induced by an acid model. Scanning electron
      microscopy (SEM) was used to examine the ultrastructure, while energy dispersive
      X-ray (EDX) and X-ray diffraction (XRD) analysis were employed to investigate the
      changes in the chemical composition of surface dentine with demineralization.
      RESULTS: Two kinds of equivalent circuits that matched the histological structure
      of dentine were used to fit the EIS data. The parameters R(d), which is the
      resistance of the bulk of dentine layer and R(ct), which is the charge transfer
      associated with the penetration of electrolyte into the dentinal tubules,
      decreased with increasing duration of demineralization. SEM images showed that
      the smear layer on the dentine and peritubular dentine disappeared with
      demineralization. The EDX results showed that the content of calcium and
      phosphorus decreased consistently with the decreasing content of HAP as shown by
      the XRD results. The findings from this study suggested that the changes in R(d)
      and R(ct) determined by the EIS corresponded well with the variation in structure
      and composition of dentine. CONCLUSIONS: EIS could be employed to monitor
      structural and chemical compositional changes induced by acid-demineralization on
      dentine surface.

PMID- 18818009
TI  - Self-assembly in aqueous solution of a modified amyloid beta peptide fragment.
AB  - The self-assembly in films dried from aqueous solutions of a modified amyloid
      beta peptide fragment is studied. We focus on sequence Abeta(16-20), KLVFF,
      extended by two alanines at the N-terminus to give AAKLVFF. Self-assembly into
      twisted ribbon fibrils is observed, as confirmed by transmission electron
      microscopy (TEM). Dynamic light scattering reveals the semi-flexible nature of
      the AAKLVFF fibrils, while polarized optical microscopy shows that the peptide
      fibrils crystallize after an aqueous solution of AAKLVFF is matured over 5 days.
      The secondary structure of the fibrils is studied by FT-IR, circular dichroism
      and X-ray diffraction (XRD), which provide evidence for beta-sheet structure in
      the fibril. From high resolution TEM it is concluded that the average width of an
      AAKLVFF fibril is (63+/-18) nm, indicating that these fibrils comprise beta
      sheets with multiple repeats of the unit cell, determined by XRD to have b and c
      dimensions 1.9 and 4.4 nm with an a axis 0.96 nm, corresponding to twice the
      peptide backbone spacing in the antiparallel beta-sheet.

PMID- 18818010
TI  - Molecular dynamics simulations of the bacterial periplasmic heme binding proteins
      ShuT and PhuT.
AB  - ShuT and PhuT are two periplasmic heme binding proteins that shuttle heme between
      the outer and inner membranes of the Gram-negative bacteria. Periplasmic binding
      proteins (PBPs) generally exhibit considerable conformational changes during the
      ligand binding process, whereas ShuT and PhuT belong to a class of PBPs that do
      not show such behavior based on their apo and holo crystal structures. By
      employing a series of molecular dynamic simulations on the ShuT and the PhuT, the
      dynamics and functions of the two PBPs were investigated. Through monitoring the
      distance changes between the two conserved glutamates of ShuT and PhuT, it was
      found the two PBPs were more flexible than previously assumed, exhibiting obvious
      opening-closing motions which were more remarkable in the apo runs of ShuT. Based
      on the results of the domain motion analysis, large scale conformational
      transitions were found in all apo runs of ShuT and PhuT, hinting that the domain
      motions of the two PBPs may be intrinsic. On the basis of the results of the
      principle component analysis, distinct opening-closing and twisting motion
      tendencies were observed not only in the apo, but also in the holo simulations of
      the two PBPs. The Gaussian network model was applied in order to analyze the
      hinge bending regions. The most important bending regions of ShuT and PhuT are
      located around the midpoints of their respective connecting helixes. Finally, the
      flexibilities and the details of the simulations of ShuT and PhuT were discussed.
      Characterized by the remarkably large flexibilities, the loop constituted by Ala
      169, Gly170 and Gly171 of ShuT and the beta-turn constituted by Ala176, Gly177
      and Gly178 of PhuT may be important for the functions of the two PBPs.
      Furthermore, the Asn254 of ShuT and the Arg228 of PhuT may be indispensable for
      the binding or unbinding of heme, since it is involved in the important hydrogen
      bonding to the propionate side-chains of heme.

PMID- 18818011
TI  - Clinically inapparent bilateral adrenal masses due to histoplasmosis.
AB  - Detection of bilateral adrenal masses in any patient often presents a management
      dilemma. Despite extensive imaging, positron emission tomography (PET) scanning,
      and fine needle aspiration biopsy (FNAB), a definite diagnosis may not be
      reached. We report an unusual case of bilateral adrenal mass diagnosed as
      histoplasmosis postoperatively and managed successfully by laparoscopy. Focus is
      placed on the role of laparoscopic adrenalectomy (LA) as a diagnostic and
      therapeutic tool in such patients.

PMID- 18818012
TI  - hCCR4/cNOT6 targets DNA-damage response proteins.
AB  - Radio and chemotherapy are the election options besides surgical resection, in
      cancer treatment. However, resistance to chemotherapy limits the effectiveness of
      therapy in the clinic. An improved knowledge of the mechanisms underlying the
      resistance to treatment would generate new therapeutic strategies. Genetic
      suppressor elements (GSEs) are short, biologically active, cDNA fragments that
      interfere with the function of their cognate gene. By selection of genetic
      suppressor elements (GSEs) conferring resistance to cisplatin, we identified the
      GSE11, that corresponds to the hCCR4/CNOT6 gene that mediates cellular
      sensitivity to the drug. Expression of GSE11-hCCR4 reduces hCCR4 protein levels
      in cells. Targeting hCCR4 with GSE11 or with siRNA, decreases sensitivity of
      mammalian cells to DNA-damaging agents. Overexpression of hCCR4 targets Chk2
      following exposure to cisplatin, without interfering with the upstream ATM/ATR
      pathway, however histone gammaH2AX is strongly phosphorylated in these cells
      compared to control cells. Our results uncover a new function for a human protein
      involved in chemotherapy response. This finding introduces a new pharmacological
      target in the treatment of solid tumours.

PMID- 18818013
TI  - Adsorption isotherms, kinetics, thermodynamics and desorption studies of 2,4,6
      trichlorophenol on oil palm empty fruit bunch-based activated carbon.
AB  - The adsorption characteristics of 2,4,6-trichlorophenol (TCP) on activated carbon
      prepared from oil palm empty fruit bunch (EFB) were evaluated. The effects of TCP
      initial concentration, agitation time, solution pH and temperature on TCP
      adsorption were investigated. TCP adsorption uptake was found to increase with
      increase in initial concentration, agitation time and solution temperature
      whereas adsorption of TCP was more favourable at acidic pH. The adsorption
      equilibrium data were best represented by the Freundlich and Redlich-Peterson
      isotherms. The adsorption kinetics was found to follow the pseudo-second-order
      kinetic model. The mechanism of the adsorption process was determined from the
      intraparticle diffusion model. Boyd plot revealed that the adsorption of TCP on
      the activated carbon was mainly governed by particle diffusion. Thermodynamic
      parameters such as standard enthalpy (DeltaH degrees ), standard entropy (DeltaS
      degrees ), standard free energy (DeltaG degrees ) and activation energy were
      determined. The regeneration efficiency of the spent activated carbon was high,
      with TCP desorption of 99.6%.

PMID- 18818014
TI  - Adsorptive removal of Erythrosine dye onto activated low cost de-oiled mustard.
AB  - The present paper is aimed to investigate and develop cheap adsorption methods
      for colour removal from wastewater using waste material de-oiled mustard as
      adsorbent. De-oiled mustard, a biosorbent, was successfully utilized for removing
      a water-soluble xanthene dye, Erythrosine from wastewater. Kinetic studies of
      adsorption of Erythrosine at de-oiled mustard were carried out at 30 degrees C,
      using aqueous solutions with 5 x 10(-5)M concentration of Erythrosine. The
      adsorption process followed a pseudo-first order model. The equilibrium process
      can be well described by both Freundlich and Langmuir models, at 30, 40 and 50
      degrees C. Free energy of adsorption (DeltaG degrees ), enthalpy (DeltaH degrees
      ), and entropy (DeltaS degrees ) changes were calculated to predict the nature of
      adsorption. The estimated values for DeltaG degrees were -12.81 x 10(3) and 
      12.57 x 10(3) over activated carbon and activated de-oiled mustard at 203 K (30
      degrees C), indicate toward a spontaneous process. The positive value for DeltaH
      degrees indicates that the adsorption of Erythrosine dye to de-oiled mustard is
      an endothermic process.

PMID- 18818015
TI  - The potential of the acetonitrile biodegradation by Mesorhizobium sp. F28.
AB  - Mesorhizobium sp. F28 was used in the NHase/amidase enzyme system to convert
      acetonitrile into acetamide and acetic acid, and the cells grew with the
      production of acetic acid. The NHase activity of the strain F28 was 78 U mg(
      1)dcw, observed in the conversion of 19.5mM acetonitrile at 0.2h. As the initial
      pH value was between 6.5 and 8.3, 18.3mM acetonitrile completely converted into
      acetamide within 2h and the accumulation of acetamide subsequently converted into
      acetic acid and ammonia within 46h. When 20.3mM acetamide was added in the
      medium, the conversion rate of acetonitrile was 80% at 2h and the conversion rate
      of the accumulative acetamide was slightly affected. The concentrations of acetic
      acid and ammonia were respectively 6.01 and 6.68 mM at 46h. The addition of
      acetic acid decreased the activities of the NHase and amidase. The conversion
      rate of acetonitrile was 94% at 9.5h and traces of acetic acid (0.25 mM) and
      ammonia (0.29 mM) were produced. The effects of product-inhibition indicated that
      the appropriate operation of bioreactor would be beneficial for Mesorizobium sp.
      F28 to degrade acetonitrile continuously.

PMID- 18818016
TI  - Degradation of n-butyl benzyl phthalate using TiO2/UV.
AB  - n-Butyl benzyl phthalate (BBP) has been classified as endocrine disrupting
      compound and priority pollutant. Effects of TiO(2) dosage, pH, initial BBP
      concentration and co-existing substances on the degradation of BBP by TiO(2)/UV
      process were investigated. The optimal TiO(2) dosage and pH value for the BBP
      degradation were 2.0gL(-1) and 7.0, respectively. The degradation rate of BBP by
      TiO(2)/UV process could be fitted pseudo-first-order kinetics. The effects of co
      existing substances on the degradation rate of BBP revealed that some anions
      (such as BrO(3)(-), ClO(4)(-) and Cr(2)O(7)(2-)) could enhance BBP degradation,
      and other anions would restrain BBP degradation. The sequence of inhibition was
      PO(4)(3-)>CO(3)(2-)>NO(3)(-)>SO(4)(2-)>Cl(-). The cations K(+), Na(+), Mg(2+) and
      Ca(2+) had the restrained effect on the BBP degradation, and the effect of Ca(2+)
      was the strongest among four cations tested. The organic compounds acetone and
      methanol decreased the degradation rate of BBP. The major intermediates of BBP
      degradation were identified as mono-butyl phthalate, mono-benzyl phthalate and
      phthalic acid, and a primary degradation mechanism was proposed.

PMID- 18818017
TI  - Physicochemical characterization and Bioremediation perspective of textile
      effluent, dyes and metals by indigenous Bacteria.
AB  - Physicochemical and bacteriological status of a local textile mill effluent
      showed considerably high values of temperature (40 degrees C), pH (9.50), EC
      (3.57mus/m), BOD (548mgl(-1)), COD (1632mgl(-1)), TSS (5496mgl(-1)), TDS
      (2512mgl(-1)), heavy metals ions (0.28-6.36mgl(-1)) and color above the
      prescribed fresh water limits. However, a considerable decline in almost all
      pollution indicators from source to sink indicated signs of natural remediation.
      Ten bacteria strains isolated from effluent showed comparatively higher
      resistance (MRL) (mgl(-1)) (average) for 10 heavy metals than against four
      structurally different dyes tested on solid media of mineral salt. Overall
      bacterial resistance was quite high against Fe(3+) (2820), Cr(3+) (1203), Zn(2+)
      (1122), Mn(2+) (804) and Pb(2+) (435), whereas, it varied amid 300-500 in four
      dyes. Bacterial decolorization/degradation of dyes indicated on solid media was
      confirmed through experiments carried out in liquid broth.

PMID- 18818018
TI  - Arsenic removal by a waste metal (hydr)oxide entrapped into calcium alginate
      beads.
AB  - In this work, a solid waste material from an electroplating industrial plant has
      been investigated for As(III) and As(V) sorption. This sorbent, a mixture of
      mainly Fe(III) and Ni(II) (hydr)oxides, has been used both in its native form and
      entrapped in calcium alginate. The effect of sorbent concentration in the gel
      bead, solution pH, contact time and As(III) and As(V) concentration on sorption
      has been studied. Furthermore the effect of the gel matrix has been investigated.
      A 10% (w/v) of (hydr)oxide in the gel beads was found to provide both spherical
      beads shape and good sorption performance. Solution pH was found to exert a
      stronger influence in As(V) than in As(III) sorption. The optimum pH range
      resulted to be within 5-10 for As(III) and within 6-9 for As(V). Taking into
      account these results, pH 8 was chosen for further sorption experiments.
      Equilibrium was reached after 48 h contact time for the studied systems. Kinetics
      data of both As(III) and As(V) onto native (hydr)oxide (O) and entrapped in
      calcium alginate beads (10% O-CA) were successfully modelled according to pseudo
      first and pseudo-second order equations. Sorption equilibrium data were evaluated
      by the Langmuir isotherm model and the maximum capacity q(max) were 77.4 and
      126.5 mg g(-1) for As(III) on O and 10% O-CA, and 26.8 and 41.6 mg g(-1) for
      As(V) on O and 10% O-CA, respectively. The entrapment of the (hydr)oxide in a
      calcium alginate gel matrix improved the As(III) and As(V) sorption by 60%.

PMID- 18818019
TI  - Halogenating reaction activity of aromatic organic compounds during disinfection
      of drinking water.
AB  - The halogenating reactions of five aromatic organic compounds (AOCs) with aqueous
      chlorine (HOCl/OCl(-)) and aqueous bromine (HOBr/OBr(-)) were studied with an aim
      to compare the formation properties of haloacetic acids (HAAs) for the
      corresponding chlorination or bromination reactions of AOCs, respectively. The
      experiment results indicated that the HAAs substitution efficiency for the
      bromination reactions of AOCs was greater than that for the chlorination
      reactions, and the formation of HAAs had a strong dependence on the chemical
      structure of AOCs. The chlorination or bromination reaction activities for the
      AOCs with electron donating functional groups were higher than that for them with
      electron withdrawing functional groups. The kinetic experiments indicated that
      the reactions of aqueous bromine with phenol were faster than those of aqueous
      chlorine with phenol and the halogen consumption exhibited rapid initial and
      slower consumption stages for the reactions of phenol with aqueous chlorine and
      bromine, respectively. In addition, the HAAs production for the chlorination
      reaction of phenol decreased with the increase of pH. These conclusions could
      provide the valuable information for the effective control of the disinfection by
      products during drinking water treatment operation.

PMID- 18818020
TI  - Photodegradation of rhodamine B under visible light by bimetal codoped TiO2
      nanocrystals.
AB  - In the search for efficient photocatalysts working under visible light, we have
      investigated the effect of metal ions (Bi/Co, Fe/Co) codoping on the
      photocatalytic activity of TiO(2) prepared by stearic acid gel method. UV-vis
      spectra revealed that doped Co enhanced the absorbency of TiO(2) under visible
      light, and Bi/Co codoped TiO(2) showed higher absorbance than Fe/Co codoped
      TiO(2). The photoreaction based on the prepared samples for photodegradation of
      20mg/l rhodamine B solution was examined. The results showed that
      Fe(0.1%)/Co(0.4%) codoped TiO(2) had the highest photoactivity among all as
      prepared samples under visible light, though less absorbency of visible light,
      indicating that the photoactivity not only benefits from absorbency but also
      relates to the cooperative effect of the two dopants.

PMID- 18818021
TI  - Characterization of wastewater from the Brazilian TNT industry.
AB  - The objective of this work was to characterize the effluent originating from a
      Brazilian TNT production industry. Analyses were performed using physical,
      chemical, spectroscopic and ecotoxicological assays, which demonstrated that the
      effluent had a significant pollution potential, mainly due to the low pH and high
      concentration of TNT (156+/-10mgL(-1)). The results also demonstrated that the
      effluent presented significant acute toxicity, and could cause countless damages
      if released into the receiving body without being adequately treated first. The
      observed pollution potential justifies studies to evaluate treatment technologies
      or recover the residue generated in the TNT industry.

PMID- 18818022
TI  - Severity of acute pain after childbirth, but not type of delivery, predicts
      persistent pain and postpartum depression.
AB  - Cesarean delivery rates continue to increase, and surgery is associated with
      chronic pain, often co-existing with depression. Also, acute pain in the days
      after surgery is a strong predictor of chronic pain. Here we tested if mode of
      delivery or acute pain played a role in persistent pain and depression after
      childbirth. In this multicenter, prospective, longitudinal cohort study, 1288
      women hospitalized for cesarean or vaginal delivery were enrolled. Data were
      obtained from patient interviews and medical record review within 36 h
      postpartum, then via telephone interviews 8 weeks later to assess persistent pain
      and postpartum depressive symptoms. The impact of delivery mode on acute
      postpartum pain, persistent pain and depressive symptoms and their
      interrelationships was assessed using regression analysis with propensity
      adjustment. The prevalence of severe acute pain within 36 h postpartum was 10.9%,
      while persistent pain and depression at 8 weeks postpartum were 9.8% and 11.2%,
      respectively. Severity of acute postpartum pain, but not mode of delivery, was
      independently related to the risk of persistent postpartum pain and depression.
      Women with severe acute postpartum pain had a 2.5-fold increased risk of
      persistent pain and a 3.0-fold increased risk of postpartum depression compared
      to those with mild postpartum pain. In summary, cesarean delivery does not
      increase the risk of persistent pain and postpartum depression. In contrast, the
      severity of the acute pain response to childbirth predicts persistent morbidity,
      suggesting the need to more carefully address pain treatment in the days
      following childbirth.

PMID- 18818023
TI  - Longitudinal prediction of early childhood discipline styles among heavy drinking
      parents.
AB  - This study sought to examine predictors of parenting trajectories in a sample of
      heavy drinking and abstaining/light drinking parents. Mixture modeling was used
      to estimate trajectories of parental discipline styles over time. Two dimensions
      of parenting were examined: laxness and overreactivity. Changes in these
      dimensions were examined for each parent. Trajectories for mothers and fathers
      were very similar and were generally stable from 18 months to 5-6 years child
      age. Fathers' binge drinking was associated with high levels of both paternal and
      maternal overreactivity. Mothers with depressed affect had the highest levels of
      overreactivity, whereas fathers reporting depressed affect were more likely to
      have moderate levels of laxness. Mothers with high levels of marital satisfaction
      were more likely to have partners in the stable low overreactivity group.
      Findings begin to elucidate the nature of early family processes that may
      contribute to maladaptive child outcomes in heavy drinking families.

PMID- 18818024
TI  - Influence of phase-related variability in premenstrual symptomatology, mood,
      smoking withdrawal, and smoking behavior during ad libitum smoking, on smoking
      cessation outcome.
AB  - Emerging evidence suggests that women have a more difficult time quitting smoking
      than men-possibly due, in part, to sex hormones. The present study characterized
      mood, premenstrual symptomatology, and smoking withdrawal, as well as smoking
      behavior, in the follicular and luteal phases during ad libitum smoking in 25
      women intending to quit. We also investigated the possible influence of phase
      related variability in these measures on likelihood of study adherence and
      smoking cessation. We found that premenstrual symptomatology, as well as some
      measures of mood and smoking withdrawal, were significantly higher during the
      luteal phase than in the follicular phase. Cigarettes/day did not vary by
      menstrual cycle phase. Phase-related variability in premenstrual symptomatology
      [F(3, 20)=2.82, p=0.0650)] and urge to smoke [F(2, 21)=4.85, p=0.0186)] were
      associated with relapse. These data support the inference that sex hormones
      influence smoking cessation outcome. This knowledge may contribute to the
      development of more rational and effective smoking cessation interventions for
      women.

PMID- 18818025
TI  - Breast cancer tumor markers: worthless or beneficial?

PMID- 18818026
TI  - Increased levels of adiponectin and resistin in alcohol dependence--possible link
      to craving.
AB  - Recent studies suggested a role of appetite regulating peptides like leptin and
      ghrelin in alcohol dependence and particularly in the neurobiology of alcohol
      craving. Aim of the present study was to investigate alterations of the
      adipocytokines adiponectin and resistin in alcohol-dependent patients. We
      analyzed a sample of 88 patients at admission for alcohol detoxification and
      after 1 week of withdrawal treatment in comparison to 89 healthy controls.
      Adiponectin and resistin serum levels were measured using commercial ELISA kits.
      The extent of alcohol craving was obtained using the Obsessive Compulsive
      Drinking Scale (OCDS). Adiponectin and resistin serum levels were significantly
      elevated in patients with alcohol dependence at both dates (admission and after 1
      week of treatment) compared to healthy controls. Adiponectin decreased
      significantly during the course of withdrawal (T=3.44, p=0.001) while resistin
      serum levels showed a slight increase (T=-1.83, p=0.071). In a multivariate
      approach the extent of alcohol craving was significantly associated with
      adiponectin but not with resistin serum levels in male patients (Beta=-0.255,
      p=0.025). Results for female patients were not significant. Our findings provide
      first evidence for an alteration of the adipocytokines adiponectin and resistin
      during alcohol withdrawal. Furthermore, adiponectin may be involved in the
      neurobiology of alcohol craving, possibly via its effects on the hypothalamic
      circuits.

PMID- 18818027
TI  - Clinical characteristics of treatment-seeking adolescents with opioid versus
      cannabis/alcohol use disorders.
AB  - OBJECTIVES: To assess the clinical characteristics of adolescents with DSM-IV
      opioid use disorder (OUD) and compare them to adolescents with cannabis/alcohol
      use disorders. METHOD: 94 adolescents (ages 14-18 years) with a current OUD and
      74 adolescents with a current non-OUD cannabis/alcohol use disorders were
      recruited from admissions, predominantly residential, to a substance abuse
      treatment program in Baltimore, ML. Participants were assessed cross-sectionally
      using standardized interviews and self-reports. Chi-square, t-tests and ANCOVA
      (adjusting for age, gender and treatment setting, race and residence) were
      performed to determine group differences on demographic, substance use,
      psychiatric and HIV-risk behaviors; logistic regression analyses, both unadjusted
      and adjusted for the above five factors were conducted to assess the strength of
      associations. RESULTS: The OUD group was more likely to be Caucasian, to have
      dropped out of school and to live in the suburbs (trend). They also had greater
      substance use severity with higher proportion of current sedative and multiple
      substance use disorders (SUD). There were generally no differences in rates of
      criminal behaviors. Both groups had high rates of current psychiatric disorders
      (83% vs. 78%, n.s.) but the OUD adolescents reported higher depressive symptoms,
      mostly in the moderate range. Injection drug use (IDU) and needle sharing was
      almost exclusive to the OUD group, while both groups reported similar high rates
      of risky sexual behaviors. CONCLUSIONS: While there were similarities between the
      two groups, OUD adolescents evidenced greater impairment in academic, substance
      use, depressive symptom and IDU-related HIV-risk areas. Findings suggest poorer
      long-term prognosis and highlight the need for specialized interventions for
      treatment-seeking OUD adolescents.

PMID- 18818028
TI  - Delay discounting by the children of smokers and nonsmokers.
AB  - This research compared delay discounting in mothers and their children (12 or 13
      years of age). Half of the mothers (n=15) were current smokers, and the other
      half (n=15) reported never smoking. Considerable research has shown that adult
      smokers discount more by delay than nonsmokers, and that parent smoking is a risk
      factor for adolescent smoking. Thus, it was hypothesized that the mothers who
      smoked would discount more by delay than the mothers who had never smoked. Also,
      it was expected that children at increased risk for smoking (i.e., mother is
      smoker) would discount more by delay than children at lower risk for smoking
      (i.e., mother is nonsmoker). The results confirmed these hypotheses: mothers who
      smoked discounted significantly more than nonsmoking mothers; and, in a parallel
      fashion, children with mothers who smoked discounted significantly more than
      children of nonsmokers. These findings indicate that delay discounting may be a
      behavioral risk factor for adolescent cigarette smoking that predates any
      substantial use of nicotine.

PMID- 18818029
TI  - Continuous monitoring of bovine spongiform encephalopathy rapid test performance
      by weak positive tissue controls and quality control charts.
AB  - Bovine spongiform encephalopathy (BSE) rapid tests and routine BSE-testing
      laboratories underlie strict regulations for approval. Due to the lack of BSE
      positive control samples, however, full assay validation at the level of
      individual test runs and continuous monitoring of test performance on-site is
      difficult. Most rapid tests use synthetic prion protein peptides, but it is not
      known to which extend they reflect the assay performance on field samples, and
      whether they are sufficient to indicate on-site assay quality problems. To
      address this question we compared the test scores of the provided kit peptide
      controls to those of standardized weak BSE-positive tissue samples in individual
      test runs as well as continuously over time by quality control charts in two
      widely used BSE rapid tests. Our results reveal only a weak correlation between
      the weak positive tissue control and the peptide control scores. We identified
      kit-lot related shifts in the assay performances that were not reflected by the
      peptide control scores. Vice versa, not all shifts indicated by the peptide
      control scores indeed reflected a shift in the assay performance. In conclusion
      these data highlight that the use of the kit peptide controls for continuous
      quality control purposes may result in unjustified rejection or acceptance of
      test runs. However, standardized weak positive tissue controls in combination
      with Shewhart-CUSUM control charts appear to be reliable in continuously
      monitoring assay performance on-site to identify undesired deviations.

PMID- 18818030
TI  - Detection of Brachyspira hyodysenteriae, Lawsonia intracellularis and Brachyspira
      pilosicoli in feral pigs.
AB  - Feral pigs are recognized as being a potential reservoir of pathogenic
      microorganisms that can infect domestic pigs and other species. The aim of this
      study was to investigate whether feral pigs in Western Australia were colonized
      by the pathogenic enteric bacteria Lawsonia intracellularis, Brachyspira
      hyodysenteriae and/or Brachyspira pilosicoli. A total of 222 feral pigs from
      three study-populations were sampled. DNA was extracted from faeces or colonic
      contents and subjected to a previously described multiplex PCR for the three
      pathogenic bacterial species. A subset of 61 samples was cultured for Brachyspira
      species. A total of 42 (18.9%) of the 222 samples were PCR positive for L.
      intracellularis, 18 (8.1%) for B. hyodysenteriae and 1 (0.45%) for B. pilosicoli.
      Four samples were positive for both L. intracellularis and B. hyodysenteriae.
      Samples positive for the latter two pathogens were found in pigs from all three
      study-sites. A strongly haemolytic B. hyodysenteriae isolate was recovered from
      one of the 61 cultured samples. Comparison of a 1250-base pair region of the 16S
      rRNA gene amplified from DNA extracted from the isolate and five of the B.
      hyodysenteriae PCR positive faecal samples helped confirm these as being from B.
      hyodysenteriae. This is the first time that B. hyodysenteriae has been detected
      in feral pigs. As these animals range over considerable distances, they present a
      potential source of B. hyodysenteriae for any domesticated pigs with which they
      may come into contact.

PMID- 18818031
TI  - Detection of Fusobacterium equinum on footrot infected hooves of sheep and
      cattle.

PMID- 18818032
TI  - Quality of life in climacteric Chilean women treated with low-dose estrogen.
AB  - OBJECTIVES: To evaluate the impact of low-dose oral estrogen therapy on the
      health-related quality of life (HRQoL) in 45-64-year-old women from the East
      Metropolitan Health Service (SSMO) in Santiago, Chile. MATERIAL AND METHODS: We
      conducted an observational cross-sectional study. A random population sample of
      women between 45 and 64 years of age was obtained through an invitation to
      contact one of 15 primary health care centers of the SSMO of Santiago, Chile. Out
      of the 927 women who were originally contacted, 844 women were able to complete
      the Menopausal Rating Scale (MRS) questionnaire. Information about demographic
      parameters, health issues, and modality of hormonal therapy (HT) were registered.
      Three groups were compared: group 1 (n=647; non-users of HT), group 2 (n=82;
      users of low-dose oral estrogen HT), and group 3 (n=115; users of non low-dose
      estrogens HT). RESULTS: There were no differences among groups in terms of
      demographic and health issue parameters. The results of the MRS scores (total
      score and somatic, psychological and urogenital domain scores) showed significant
      differences across the 3 study groups, with more favorable results for HRQoL in
      groups 2 and 3 (p<0.01 for total, somatic, and psychological scores; p=0.05 for
      urogenital score). CONCLUSION: Climacteric women in the 45-64 age range using HT
      were shown to have a more favorable impact on HRQoL than non-HT users. Women
      using low-dose oral estrogen HT had a positive effect on HRQoL, similar to that
      obtained using non low-dose estrogen regimens.

PMID- 18818033
TI  - A fatal case due to combined toxicity of psychotropic drugs.

PMID- 18818034
TI  - Raman spectroscopy offers great potential for the nondestructive confirmatory
      identification of body fluids.
AB  - Raman spectroscopy was used to compare body fluids commonly found at crime scenes
      in a nondestructive manner. The dry traces of semen, vaginal fluid, sweat,
      saliva, and blood were analyzed using confocal Raman microscopy with a 785-nm
      excitation. The results show that the five fluids can be differentiated from one
      another by visual comparison of their Raman spectra, and that the laser radiation
      does not damage the sample. The Raman signature of each body fluid is specific
      and correlates with the known composition of the fluid. Dry traces of human and
      canine semen exhibited distinctly different Raman signatures. Overall, this
      preliminary study demonstrates the great potential of Raman spectroscopy for
      nondestructive, confirmatory identification of body fluids for forensic purposes.

PMID- 18818035
TI  - [Hepatic and renal toxicity to fluindione (Previscan)].

PMID- 18818036
TI  - Severe hepatitis due to percutaneous diclofenac.
AB  - Although it is rare, diclofenac, a nonsteroidal antiinflammatory drug, may cause
      severe liver damage,sometimes with a fatal outcome. We report the first case of a
      patient who developed severe reversible liver damage after a percutaneous
      administration of diclofenac.

PMID- 18818037
TI  - How to optimize breast ultrasound.
AB  - Breast cancer is the most common female cancer, and the second cause of cancer
      related mortality of women in our society. Mammography is the gold-standard
      method of breast imaging. However it is not an optimal screening tool, especially
      in cases of dense breast parenchyma. Even when optimally performed, its
      sensitivity ranges between 69 and 90%. Ultrasound represents an additional
      diagnostic tool that raises the detection rate of benign and malignant breast
      lesions. It is the method of choice for differentiating solid from cystic
      lesions, for further characterizing mammographic findings and better appreciating
      palpable breast lesions. B-mode ultrasonography is used in every day practice.
      Harmonic imaging and compound imaging can be used to ameliorate the image
      contrast and resolution. Colour Doppler is used for studying lesion
      vascularization however there is no consensus as to whether it really permits to
      differentiate malignancies from benign lesions. New technical developments such
      as breast elastography, 3D ultrasound and dedicated ultrasound computed aided
      diagnosis (CAD) are promising methods for the future.

PMID- 18818038
TI  - Incidental findings in healthy control research subjects using whole-body MRI.
AB  - AIM: Magnetic resonance imaging (MRI) is a powerful clinical tool used
      increasingly in the research setting. We aimed to assess the prevalence of
      incidental findings in a sequential cohort of healthy volunteers undergoing whole
      body MRI as part of a normal control database for imaging research studies.
      MATERIALS AND METHODS: 148 healthy volunteers (median age 36 years, range 21-69
      years; 63.5% males, 36.5% females) were enrolled into a prospective observational
      study at a single hospital-based MRI research unit in London, UK. Individuals
      with a clinical illness, treated or under investigation were excluded from the
      study. RESULTS: 43 (29.1%) scans were abnormal with a total of 49 abnormalities
      detected. Of these, 20 abnormalities in 19 patients (12.8%) were of clinical
      significance. The prevalence of incidental findings increased significantly with
      both increasing age and body mass index (BMI). Obese subjects had a fivefold
      greater risk of having an incidental abnormality on MRI (OR 5.4, CI 2.1-14.0).
      CONCLUSIONS: This study showed that more than one quarter of healthy volunteers
      have MR-demonstrable abnormalities. There was an increased risk of such findings
      in obese patients. This has ethical and financial implications for future imaging
      research, particularly with respect to informed consent and follow-up of those
      with abnormalities detected during the course of imaging studies.

PMID- 18818039
TI  - Anisotropic field-of-view shapes for improved PROPELLER imaging.
AB  - The Periodically Rotated Overlapping ParallEL Lines with Enhanced Reconstruction
      (PROPELLER) method for magnetic resonance imaging data acquisition and
      reconstruction has the highly desirable property of being able to correct for
      motion during the scan, making it especially useful for imaging pediatric or
      uncooperative patients and diffusion imaging. This method nominally supports a
      circular field of view (FOV), but tailoring the FOV for noncircular shapes
      results in more efficient, shorter scans. This article presents new algorithms
      for tailoring PROPELLER acquisitions to the desired FOV shape and size that are
      flexible and precise. The FOV design also allows for rotational motion which
      provides better motion correction and reduced aliasing artifacts. Some possible
      FOV shapes demonstrated are ellipses, ovals and rectangles, and any convex, pi
      symmetric shape can be designed. Standard PROPELLER reconstruction is used with
      minor modifications, and results with simulated motion presented confirm the
      effectiveness of the motion correction with these modified FOV shapes. These new
      acquisition design algorithms are simple and fast enough to be computed for each
      individual scan. Also presented are algorithms for further scan time reductions
      in PROPELLER echo-planar imaging (EPI) acquisitions by varying the sample spacing
      in two directions within each blade.

PMID- 18818040
TI  - Liquid chromatographic analysis of guanidino compounds using furoin as a new
      fluorogenic reagent.
AB  - Furoin, a benzoin analogue, was examined as novel fluorogenic reagent for the
      selective and sensitive LC determination of various guanidines after pre-column
      derivatization. The derivatization reaction was carried out at 100 degrees C for
      5 min to give adducts that were separated on a Phenomenex Synergi MAX-RP column
      and detected at lambda(em)=410 nm with lambda(ex)=325 nm. The reagent showed to
      be useful both for determining together arginine (Arg) and creatine (CT) in
      dietary supplements under elution isocratic conditions and for the simultaneous
      analysis of a variety of guanidines in biological samples (human plasma and
      urine) under elution gradient conditions. The detection limits ranged from 7 to
      25 fmol. Recovery studies showed good results for all determined guanidino
      compounds (85.6-106.2%; R.S.D.=1.1-6.2%).

PMID- 18818041
TI  - Quantification of pegylated phospholipids decorating polymeric microcapsules of
      perfluorooctyl bromide by reverse phase HPLC with a charged aerosol detector.
AB  - Polyethylene glycol (PEG) chains covalently linked to phospholipids are often
      used in the preparation of lipid or even polymer colloidal particles to avoid
      recognition and clearance by the reticuloendothelial system and to increase their
      plasmatic half-life. To the best of our knowledge, no direct method allows yet to
      quantify these pegylated phospholipids. The aim of this work was to develop a
      method for the quantification of a typical pegylated phospholipid, 1,2-distearoyl
      sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000], DSPE
      PEG2000, associated to polymeric microcapsules of perfluorooctyl bromide (PFOB).
      Reverse phase high-performance liquid chromatography (HPLC) was used, coupled
      with a corona charged aerosol detection (HPLC-CAD). Calibrations standards
      consisted of plain microcapsules and pegylated phospholipids (DSPE-PEG2000) in
      the concentration range of 2.23-21.36 microg/mL (0.22-2.14 microg injected).
      Calibration curve was evaluated with two different model, linear and power model.
      The power model describes experimental values better than the linear model, for
      pegylated phospholipids with the CAD detector. The correlation coefficient for
      the power model was 0.996, and limits of detection and quantification obtained
      were 33 and 100 ng, respectively. This method proved to be selective and
      sensitive; the accuracy of the method ranged from 90 to 115% and the relative
      standard deviation was <or=5.3%. Pegylated phospholipids associated to
      microcapsules, as well as the phospholipids and total phospholipids in the
      suspensions were successfully quantified in three different preparations of
      microcapsules.

PMID- 18818042
TI  - Development of a liquid chromatography-tandem mass spectrometry method for an
      euthanasic veterinarian drug: Tanax.
AB  - A development of a rapid and sensitive LC-MS/MS method for the simultaneous
      detection of active ingredients of the euthanasic veterinarian drug Tanax mixture
      is described. The method proposed, with a retention time of few minutes (6 min)
      was developed for an equine serum sample with solid-phase extraction (S.P.E).
      This S.P.E. procedure has been revealed useful for the determination of very low
      concentrations of Tanax analytes (0.05-1 ng/ml). The method was validated in
      terms of specificity/selectivity, sensitivity, recovery and precision.

PMID- 18818043
TI  - An improved LC-ESI-MS-MS method for simultaneous quantitation of rosiglitazone
      and N-desmethyl rosiglitazone in human plasma.
AB  - A fast, sensitive, and selective method for the simultaneous quantitation of
      rosiglitazone and N-desmethyl rosiglitazone in human plasma, using rosiglitazone
      d(4) and N-desmethyl rosiglitazone-d(4) as the respective internal standards, has
      been developed and validated. The analytes in human plasma (50 microL sample
      aliquot) were isolated through supported liquid/liquid extraction (SLE) and
      separated by isocratic HPLC over a 3-min period. The precursor and product ions
      were detected by ESI-MS-MS with multiple reaction monitoring (MRM) in a triple
      quadrupole mass spectrometer. For both rosiglitazone and N-desmethyl
      rosiglitazone, the lower limit of quantitation (LLOQ) was 1.00 ng/mL, and the
      quantitation range was 1.00-500 ng/mL (with an average correlation coefficient
      >0.9990). The intra-assay and inter-assay precision had a maximum %CV of 9.37%,
      and the accuracy had a maximum %difference from theoretical of 12.7%. This method
      was applied to a clinical study where 16 healthy volunteers were administered a
      single dose of 4.0mg rosiglitazone. The pharmacokinetic parameters of
      rosiglitazone and N-desmethyl rosiglitazone were consistent with the results
      reported in the literature.

PMID- 18818044
TI  - Rupture of the pectoralis major: a case report and review.
AB  - BACKGROUND: Rupture of the pectoralis major muscle is a rare clinical entity that
      is becoming more common due to the increasing popularity of weightlifting and
      recreational sports. Due to the rarity of this condition, it may be missed at
      initial presentation and inappropriately treated, potentially leading to
      increased disability. OBJECTIVES: This case highlights the mechanism of injury,
      clinical features, diagnosis, and treatment of rupture of the pectoralis major.
      CASE REPORT: The patient was a 31-year-old male bodybuilder who presented to the
      Emergency Department with acute pain and swelling in the left axilla after
      performing a bench press with a 400-pound barbell. The diagnosis of pectoralis
      major rupture was suspected and confirmed by magnetic resonance imaging, and
      early surgical repair was performed. CONCLUSION: The most common mechanism of
      injury is excessive tension on a maximally contracted pectoralis major muscle.
      Weightlifting, specifically bench pressing, is a common cause. The diagnosis can
      usually be made based on a patient's history and physical examination, but
      shortly after injury, the diagnosis may be obscured by severe pain and swelling.
      Magnetic resonance imaging is the imaging modality of choice when the diagnosis
      remains unclear, and can avoid surgical delays. Early diagnosis and treatment
      within 3 to 8 weeks after the injury has the advantage of avoiding adhesions and
      muscle atrophy, and can prevent a delayed return to normal activities. Given the
      trend toward improved results with early surgical repair of complete rupture, it
      is important to raise awareness about pectoralis major muscle injury among
      Emergency Physicians to prevent missed or delayed diagnosis and repair.

PMID- 18818045
TI  - Does the smoking status of general practitioners affect the efficacy of smoking
      cessation counselling?
AB  - OBJECTIVE: To examine the association between the smoking status of general
      practitioners (GPs) and abstinence rates among patients receiving GP-delivered
      brief advice for smoking cessation. METHODS: A quasi-experimental multilevel
      study with follow-up assessments at 6, 12, 18, and 24 months after baseline was
      conducted using a random sample of 39 general practices in a defined area
      (participation rate=87.2%). Patients aged 18-70 were consecutively screened for
      smoking status (n=11,560) over the course of 3 weeks and were assigned to a
      control group (week 1), a computer expert system intervention (week 2), or a
      personal counselling intervention with the GP (week 3). For the current analysis,
      patients participating in study week 2 were excluded. A total of 1260 patients
      fulfilled the inclusion criteria and 80.2% took part: 609 patients in study week
      1 and 402 patients from study week 3. GPs participated in a training session
      concerning smoking counselling, which was held between study weeks 2 and 3. Self
      reported 4-week and 6-month prolonged abstinence measures at the 6-, 12-, 18-,
      and 24-month follow-ups were assessed. RESULTS: The smoking status of the GP was
      neither significantly related to 4-week prolonged abstinence nor 6-month
      prolonged abstinence among patients in a main effects model. Further modelling
      revealed that the intervention group modified the effect of the non-smoking
      status of the GP on the likelihood to quit smoking. A significant interactive
      effect was found between the non-smoking status of the GP and the intervention
      group on both abstinence measures. CONCLUSION: The non-smoking status of the GP
      had a positive effect among counselled patients. PRACTICE IMPLICATIONS: The
      consideration of lifestyle behavioural variables such as the smoking status of
      the GP will be essential for further research concerning the efficacy of smoking
      interventions.

PMID- 18818046
TI  - Expression of genes related to corticotropin production and glucocorticoid
      feedback in corticotroph adenomas of dogs with Cushing's disease.
AB  - Cushing's disease caused by pituitary corticotroph adenoma is a common endocrine
      disease in dogs. A characteristic biochemical feature of corticotroph adenomas is
      their relative resistance to negative feedback by glucocorticoids. In this study,
      we examined gene expression related to adrenocorticotropic hormone (ACTH)
      production and secretion, and the negative feedback by glucocorticoids in canine
      corticotroph adenoma. We used resected corticotroph adenomas from 10 dogs with
      Cushing's disease. In order to investigate the alteration of gene expression
      between corticotroph adenoma and normal corticotrophic cells, ACTH-positive cells
      in the anterior lobe were microdissected using a laser-capture microdissection
      system, and mRNA levels of proopiomelanocortin (POMC), corticotropin releasing
      hormone receptor 1 (CRHR1), glucocorticoid receptor (GR), mineralocorticoid
      receptor (MR), and 11 beta hydroxysteroid dehydrogenase (11HSD) type 1 and type 2
      were determined using real-time RT-PCR. POMC, CRHR1, and 11HSD2 mRNA levels in
      corticotroph adenoma were greater than those in normal corticotrophic cells
      (POMC, 5.5-fold; CRHR1, 4.9-fold; 11HSD2, 4.2-fold, P<0.01, respectively). MR and
      11HSD1 mRNA levels in corticotroph adenoma were lower than those in normal
      corticotrophic cells (MR, 2.2-fold; 11HSD1, 2.9-fold, P<0.01, respectively). GR
      mRNA levels did not differ between corticotroph adenoma and normal corticotrophic
      cells. Our results may help to understand the increased ACTH production and the
      resistance to negative feedback suppression by glucocorticoids in canine
      corticotroph adenomas. These changes in gene expression may have a role in the
      growth of canine corticotroph adenoma, and help elucidate the pathophysiology of
      dogs with Cushing's disease.

PMID- 18818047
TI  - Reversal effect of substituted 1,3-dimethyl-1H-quinoxalin-2-ones on multidrug
      resistance in adriamycin-resistant K562/A02 cells.
AB  - QA1 and QA3 are the derivatives of substituted 1,3-dimethyl-1H-quinoxalin-2-ones
      that may selectively antagonize P-glycoprotein (P-gp) in multidrug resistance
      (MDR) cancer cells. Herein, we examined the reversal effect of two compounds on
      MDR in adriamycin (Adr)-induced resistant K562/A02 cells. MTT (3-[4,5
      dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide) assay showed that QA1 and
      QA3 weakly inhibited the growth of tumor cells. However, the compounds increased
      Adr-induced cytotoxicity toward K562/A02 cells. The IC(50) values of Adr toward
      K562/A02 were decreased in the presence of QA1 or QA3. The maximal reversal fold
      (RF) of QA1 and QA3 was reached 6.9 and 9.0, respectively. The action of QA1 and
      QA3 was also confirmed by the increase of intracellular Adr accumulation in
      K562/A02 cells. In mechanism study, the intracellular accumulation and efflux of
      Rh123 were measured using multilabel counter with excitation/emission wavelengths
      of 485/535nm. An increase of intracellular Rh123 and the decrease of efflux were
      observed in K562/A02 cells incubation with QA1 or QA3, indicating that the
      activity of P-gp was blocked. These results suggested that the derivatives of
      substituted 1,3-dimethyl-1H-quinoxalin-2-ones might reverse MDR in K562/A02 cells
      via inhibition activity of P-gp. QA1 and QA3 might be the candidate agents for
      reversing MDR of cancer.

PMID- 18818048
TI  - [Auto-inflammatory syndromes and pregnancy].
AB  - In familial mediterranean fever (FMF), fertility is normal in treated patients.
      There is no abnormality of spermatogenesis under usual therapeutic doses of
      colchicine. The risk of early abortion is increased if inflammatory attacks occur
      during the pregnancy. It is recommended to continue colchicine treatment during
      the conception and the pregnancy. Careful follow-up must be organized, even more
      in patients with renal amyloidosis. Breast-feeding is allowed under colchicine
      with no risk for the baby. There is no indication for systematic amniocentesis in
      FMF patients treated with colchicine.

PMID- 18818049
TI  - [Pregnancy and inflammatory myopathies].
AB  - In general, pregnancies in women with inflammatory myopathy (IM) in sustained
      remission have a favourable outcome, whereas those pregnant patients with active
      IM have an increased risk for foetal loss, intra-uterine growth retardation
      and/or prematurity. The effect of pregnancy on disease activity is variable. All
      patients with active IM need to be followed by a multidisciplinary team including
      obstetricians, rheumatologists and/or internists in close relationship with a
      neonatal intensive care unit. Maternal disease should be treated with
      corticosteroids, using the same dosage and regimen as for non-pregnant women and
      according to the disease activity and severity.

PMID- 18818050
TI  - [Occupational asthma in shrimp-processing industry: what behind all this?].

PMID- 18818051
TI  - A modified FCM algorithm for MRI brain image segmentation using both local and
      non-local spatial constraints.
AB  - Image segmentation is often required as a preliminary and indispensable stage in
      the computer aided medical image process, particularly during the clinical
      analysis of magnetic resonance (MR) brain images. In this paper, we present a
      modified fuzzy c-means (FCM) algorithm for MRI brain image segmentation. In order
      to reduce the noise effect during segmentation, the proposed method incorporates
      both the local spatial context and the non-local information into the standard
      FCM cluster algorithm using a novel dissimilarity index in place of the usual
      distance metric. The efficiency of the proposed algorithm is demonstrated by
      extensive segmentation experiments using both simulated and real MR images and by
      comparison with other state of the art algorithms.

PMID- 18818052
TI  - Association between a disrupted-in-schizophrenia 1 (DISC1) single nucleotide
      polymorphism and schizophrenia in a combined Scandinavian case-control sample.
AB  - Disrupted-in-schizophrenia-1 (DISC1), located on chromosome 1q42.1, is linked to
      rare familial schizophrenia in a large Scottish family. The chromosomal
      translocation that segregates with the disease results in a truncated protein
      that impairs neurite outgrowth and proper development of the cerebral cortex,
      suggesting that lost DISC1 function may underlie neurodevelopmental dysfunction
      in schizophrenia. DISC1 has been associated with schizophrenia in multiple
      populations, but there is little evidence of convergence across populations. In
      the present case-control study three Scandinavian samples of 837 individuals
      affected with schizophrenia and 1473 controls, were used in an attempt to
      replicate previously reported associations between single nucleotide
      polymorphisms (SNPs) in DISC1 and schizophrenia. No SNP with allele frequency
      above 10% was significantly associated with the disease after correction for
      multiple testing. However, the minor allele of rs3737597 (frequency 2%) in the 3'
      untranslated region (UTR), previously identified as a risk allele in Finnish
      families, was significantly and consistently associated with the disorder across
      the three samples, (p-value corrected for multiple testing was 0.002). Our
      results suggest that a relatively uncommon DISC1 mutation, which increases the
      susceptibility for schizophrenia may be segregating in the Scandinavian
      population, and support the view that common DISC1 SNP alleles are unlikely to
      account for a substantial proportion of the genetic risk of the disease across
      populations of European descent.

PMID- 18818053
TI  - Abnormal brain response during the auditory emotional processing in schizophrenic
      patients with chronic auditory hallucinations.
AB  - OBJECTIVE: Few neuroimaging studies have been conducted regarding clinical
      associations between auditory hallucinations (AHs) and affective disturbances in
      patients with schizophrenia. This study aimed to elucidate the neurobiological
      basis of emotional disturbances in schizophrenic patients with persisting AHs.
      METHODS: Using functional magnetic resonance imaging (fMRI), the cortical
      responsiveness during the processing of laughing and crying sounds was measured
      and compared between 14 hallucinating schizophrenic patients, 14 nonhallucinating
      schizophrenic patients and 28 normal controls. RESULTS: The hallucinating
      patients showed differential neural activities in various areas including the
      amygdala, the hippocampus, the cingulate, the prefrontal cortex, and the parietal
      cortex, compared with the nonhallucinating patients and the normal controls. In
      particular, compared with the nonhallucinators, the hallucinators revealed
      reduced activation in the left amygdala and the bilateral hippocampus during the
      processing of crying sounds. CONCLUSION: Our findings suggest that the
      persistence of AHs in schizophrenia may induce functional disturbances of the
      emotion-related interconnected neural networks, including reduced responsiveness
      in the amygdala and hippocampus to negative stimuli.

PMID- 18818054
TI  - Regional patterns and clinical correlates of basal ganglia morphology in non
      medicated schizophrenia.
AB  - Although structural changes of the basal ganglia are widely implicated in
      schizophrenia, prior findings in chronically medicated patients show that these
      changes relate to particular antipsychotic treatments. In unmedicated
      schizophrenia, local alterations in morphological parameters and their
      relationships with clinical measures remain unknown. Novel surface-based
      anatomical modelling methods were applied to magnetic resonance imaging data to
      examine regional changes in the shape and volume of the caudate, the putamen and
      the nucleus accumbens in 21 patients (19 males/2 females; mean age=30.7+/-7.3)
      who were either antipsychotic-naive or antipsychotic-free for at least 1 year and
      21 healthy comparison subjects (19 males/2 females; mean age=31.1+/-8.2).
      Clinical relationships of striatal morphology were based on exploratory analyses.
      Left and right global putamen volumes were significantly smaller in patients than
      controls; no significant global volume effects were observed for the caudate and
      the nucleus accumbens. However, surface deformation mapping results showed
      localized volume changes prominent bilaterally in medial/lateral anterior regions
      of the caudate, as well as in anterior and midposterior regions of the putamen,
      pronounced on the medial surface. A significant positive correlation was observed
      between right anterior putamen surface contractions and affective flattening, a
      core negative symptom of schizophrenia. The diagnostic effects of local surface
      deformations mostly pronounced in the associative striatum, as well as the
      correlation between anterior putamen morphology and affective flattening in
      unmedicated schizophrenia suggest disease-specific neuroanatomical abnormalities
      and distinct cortical-striatal dysconnectivity patterns relevant to altered
      executive control, motor planning, along with abnormalities of emotional
      processing.

PMID- 18818055
TI  - Successful treatment with moxifloxacin of experimental aortic valve endocarditis
      due to methicillin-resistant Staphylococcus aureus (MRSA).
AB  - Moxifloxacin (MXF) is an 8-methoxyquinolone with high activity against Gram
      positive bacteria. In an experimental model of aortic valve endocarditis (EAVE),
      the efficacy of MXF was evaluated against a strain of methicillin-resistant
      Staphylococcus aureus (MRSA). Rabbits with catheter-induced aortic valve
      vegetations were randomly assigned to a control group or to groups receiving MXF
      20 mg/kg intravenous (i.v.) twice a day (bid) or vancomycin (VAN) 30 mg/kg i.v.
      bid for a total of eight doses (4 days). Rabbits were sacrificed 15 h after the
      last dose of antibiotics. In another group, treatment with MXF was extended to 5
      days and rabbits were sacrificed 5 days after the last dose (10th dose) of MXF in
      order to detect possible relapses of endocarditis after the end of treatment
      (test-of-cure (TOC) study). Both MXF and VAN significantly reduced the bacterial
      load in vegetations (P < 0.001 vs. controls). All animals in the MXF-TOC group
      had sterile vegetations. MXF given at a dose of 20 mg/kg i.v. bid for 4 days was
      equally effective as VAN in the treatment of EAVE due to MRSA. When treatment
      with MXF was extended to 5 days, the cure rate reached 100% and no relapses of
      endocarditis were observed.

PMID- 18818056
TI  - Dopaminergic and serotonergic activity in neostriatum and nucleus accumbens
      enhanced by intranasal administration of testosterone.
AB  - Testosterone was administered intranasally in anesthetized male rats, and its
      effects on the activity of dopaminergic and serotonergic neurons in the
      neostriatum and nucleus accumbens were assessed by means of microdialysis and
      HPLC. The treatment (0.5, 1.0 or 2.0 mg/kg of testosterone or vehicle, 10 microl
      volume) was applied in both nostrils, half (5 microl) into each. Subcutaneous
      injections of testosterone (2.0, 4.0 or 8.0 mg/kg) or vehicle were tested in
      other subjects. Samples were collected for 5 h. In the neostriatum, an increase
      of dopamine occurred after 2.0 mg/kg. Serotonin levels increased after 1.0 mg/kg
      dose. In the nucleus accumbens, dopamine and serotonin increased after 1.0 mg/kg
      and 2.0 mg/kg doses. Subcutaneous administration of 8.0 mg/kg testosterone
      increased dopamine and serotonin in the neostriatum only. We conclude that
      intranasal administration of testosterone is a more efficacious way for targeting
      the brain than the subcutaneous route, and may be considered as a means to
      activate central dopaminergic and serotonergic systems.

PMID- 18818057
TI  - Resolution of (R,S)-(+/-)-glycidyl butyrate with immobilized Y-11 Trichosporon
      capitatum lipase in gelatin-containing microemulsion-based organogels.
AB  - An extracellular lipase produced by the strain of Y-11 Trichosporon capitatum was
      purified to homogeneity by ammonium sulfate precipitation and four
      chromatographic steps. The purified lipase showed enhanced activity when it was
      immobilized in gelatin-containing microemulsion-based organogels. Furthermore,
      the resolution of (R,S)-(+/-)-glycidyl butyrate by this immobilized lipase gave a
      product of (S)-(-)-glycidol with approximately 98% ee (E=96). By using chiral
      HPLC separation, (S)-(-)-glycidol was obtained in enantiopure form. Scaled-up
      reaction in 2l shake flask was also performed and the repeated use of 15 times of
      immobilized Y-11 T. capitatum lipase resulted in little loss in its activity
      (4.8%).

PMID- 18818058
TI  - Comparative study of lipolysis by PLA2 of DOPC substrates organized as
      monolayers, bilayer vesicles and nanocapsules.
AB  - The water-soluble lipolytic enzymes act at the interface of insoluble lipid
      substrates, where the catalytical step is coupled with various interfacial
      phenomena as enzyme penetration, solubilization of reaction products, loss of
      mechanical stability of organized assemblies of phospholipids molecule, etc. One
      biologically relevant example is the enzymatic hydrolysis of DOPC by PLA(2),
      which results in cleavage of phospholipids molecules into water insoluble
      lipolytic products, namely oleic acid and lysophospholipid. In general, the
      enzymatic activity depends on the substrate organization and molecular
      environment of the catalytic reaction. The lipolysis by phospholipase A(2) of
      dioleoylphosphatidylcholine substrates organized as monolayer, bilayers vesicles
      and lipid nanocapsules was studied by measuring the decrease of the surface area
      at constant surface pressure or increase of the surface pressure at constant area
      at air-water interface. A kinetic model describing the coupling of the catalytic
      act with corresponding interfacial phenomena was developed. By using the kinetic
      model the values for the global hydrolytic kinetic constants were obtained. The
      obtained value for the monolayer is five orders of magnitude higher than this
      obtained with small unilamellar vesicles and six orders of magnitude higher then
      those obtained with lipid nanocapsules. The comparison shows that the enzymatic
      catalytic act occurring in the lipid environment of the monolayer is more
      efficacious than at the vesicle and nanocapsules interfaces.

PMID- 18818059
TI  - Invitations for the Program: 6th International Congress of Pathophysiology, "Gene
      environmental Interactions in Health and Diseases", Montreal, Quebec, Canada, 27
      30 June 2010.

PMID- 18818060
TI  - [Unexpected detection of hypoxemia when consulting for abdominal pain in a
      pediatric emergency unit].

PMID- 18818061
TI  - Artificial intelligence in medicine AIME'07.

PMID- 18818062
TI  - Philosophical foundations of artificial consciousness.
AB  - OBJECTIVE: Consciousness is often thought to be that aspect of mind that is least
      amenable to being understood or replicated by artificial intelligence (AI). The
      first-personal, subjective, what-it-is-like-to-be-something nature of
      consciousness is thought to be untouchable by the computations, algorithms,
      processing and functions of AI method. Since AI is the most promising avenue
      toward artificial consciousness (AC), the conclusion many draw is that AC is even
      more doomed than AI supposedly is. The objective of this paper is to evaluate the
      soundness of this inference. METHODS: The results are achieved by means of
      conceptual analysis and argumentation. RESULTS AND CONCLUSIONS: It is shown that
      pessimism concerning the theoretical possibility of artificial consciousness is
      unfounded, based as it is on misunderstandings of AI, and a lack of awareness of
      the possible roles AI might play in accounting for or reproducing consciousness.
      This is done by making some foundational distinctions relevant to AC, and using
      them to show that some common reasons given for AC scepticism do not touch some
      of the (usually neglected) possibilities for AC, such as prosthetic,
      discriminative, practically necessary, and lagom (necessary-but-not-sufficient)
      AC. Along the way three strands of the author's work in AC--interactive
      empiricism, synthetic phenomenology, and ontologically conservative
      heterophenomenology--are used to illustrate and motivate the distinctions and the
      defences of AC they make possible.

PMID- 18818063
TI  - Introduction of trifluoromethyl group into diphenyl diselenide molecule alters
      its toxicity and protective effect against damage induced by 2-nitropropane in
      rats.
AB  - This study was undertaken to investigate if the introduction of trifluoromethyl
      (F(3)C) group into diphenyl diselenide (PhSe)(2) molecule causes acute toxicity
      in rats. It was further examined if the presence of F(3)C group in (PhSe)(2)
      molecule alters the protective effect caused by (PhSe)(2) against damage induced
      by 2-nitropropane (2-NP) in rats. To investigate the potential oral toxicity of
      (PhSe)(2) and (F(3)CPhSe)(2), rats received a single oral application of
      (PhSe)(2) (7.8-312 mg/kg) or (F(3)CPhSe)(2) (11.2-448 mg/kg). Calculated lethal
      dose (LD(50)) for (PhSe)(2) and (F(3)CPhSe)(2) was estimated to be 312 mg/kg (=1
      mmol/kg) and 234 mg/kg (=0.52 mmol/kg), respectively. Oral administration of
      (PhSe)(2) in rats did not change plasma alanine and aspartate aminotransferase
      activities (AST and ALT) as well as urea and creatinine levels. The introduction
      of F(3)C group into (PhSe)(2) molecule increased AST activity in plasma of rats.
      (PhSe)(2) (3.2 mg/kg=10 micromol/kg) and (F(3)CPhSe)(2) (4.48 mg/kg=10
      micromol/kg) protected ALT, AST and gamma-glutamyl transferase (gamma-GT)
      activities against the increase caused by oral administration of 2-NP (120 mg/kg)
      in rats. (PhSe)(2) and (F(3)CPhSe)(2) ameliorated hepatic catalase activity
      altered by 2-NP in rats. These results indicate that the chemical alteration into
      (PhSe)(2) molecule introduced toxicity and altered its protective effect against
      damage induced by 2-NP in rats.

PMID- 18818064
TI  - The in vitro and in vivo antiviral effects of salidroside from Rhodiola rosea L.
      against coxsackievirus B3.
AB  - The aim of this study was to investigate the antiviral effects of salidroside, a
      major component of Rhodiola rosea L. First, the antiviral effects of salidroside
      against coxsackievirus B3 (CVB3) were determined in vitro and in vivo. Then, the
      effect of salidroside on the mRNA expression of some important cytokines was
      measured in hearts of infected BALB/c mice by RT-PCR. Salidroside exhibited
      obvious antiviral effects both in in vitro and in vivo experiments. Salidroside
      was found to modulate the mRNA expression of interferon-gamma (IFN-gamma),
      interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-alpha), and interleukin
      2 (IL-2). In conclusion, salidroside possesses antiviral activities against CVB3
      and it may represent a potential therapeutic agent for viral myocarditis.

PMID- 18818065
TI  - Body mass index, respiratory function and bronchial hyperreactivity in allergic
      rhinitis and asthma.
AB  - BACKGROUND: Several studies have outlined a possible relationship between an
      increased body mass index (BMI) and respiratory allergic diseases, such as asthma
      and rhinitis. The aim of the study was to analyse the relationship between BMI
      and allergic diseases, including allergic rhinitis and asthma, and functional
      parameters, such as nasal airflow, FEV(1), and non-specific BHR to methacholine,
      in a cohort of navy army subjects. METHODS: The study included 100 patients with
      moderate-severe persistent allergic rhinitis alone, 100 with intermittent
      allergic asthma alone, and 100 healthy controls. All subjects were evaluated
      performing skin prick test, spirometry, and bronchostimulation test with
      methacholine. Rhinomanometry was performed in patients with rhinitis. RESULTS:
      BMI values were significantly lower in control subjects with respect to patients
      with rhinitis (P=0.0002) and with respect to patients with asthma (P<0.0001). BMI
      was also significantly higher in males with respect to females (P=0.005). A
      significant relationship has been observed between some categories of BHR and BMI
      either in patients with rhinitis (P<0.01) or in patients with asthma (P<0.01),
      whereas there was no association between BMI and functional parameters.
      CONCLUSION: This study provides the first evidence of a significant relationship
      between BMI and allergic rhinitis and between BMI and BHR in both allergic
      disorders.

PMID- 18818066
TI  - Influenza vaccination among Canadians with chronic respiratory disease.
AB  - BACKGROUND: The purposes of this study were to estimate the prevalence of recent
      influenza vaccination, to identify sociodemographic risk factors and reasons for
      non-vaccination, and to examine the association between influenza vaccination and
      respiratory medication use, among individuals with asthma and COPD in Canada.
      METHODS: Data from the 2003 Statistics Canada Canadian Community Health Survey
      (n=134,072, age 12-80+ years) were analyzed. All data were based on self-report.
      RESULTS: An estimated 36.3% and 47.9% of individuals with asthma and COPD,
      respectively, were immunized for influenza within the last year in 2003. These
      vaccination rates were relatively lower than those seen with other non
      respiratory health conditions. Respondents thinking that influenza vaccination
      was not necessary was the most frequent reason cited for non-vaccination among
      individuals with asthma and COPD. Men, non-Ontarians, younger age groups, current
      smokers, and those without a family doctor were less likely to be vaccinated
      among individuals with asthma and COPD. After controlling for potential
      sociodemographic confounders, among individuals with asthma, those vaccinated for
      influenza had significantly greater odds of using inhalers/nebulizers (OR=1.8,
      95% CI=1.3-2.4). No other significant medication use associations were observed
      among individuals with asthma and COPD. CONCLUSIONS: Recent self-reported
      influenza vaccination rates among individuals with asthma and COPD were
      relatively low. Influenza vaccination was not associated with decreased
      respiratory medication use among individuals with asthma and COPD, suggesting
      that vaccination may not help prevent exacerbations. More research is needed to
      fully clarify the role of influenza vaccination in chronic respiratory disease,
      particularly asthma, to justify policies of mass-immunization.

PMID- 18818067
TI  - A sensitive NADH and glucose biosensor tuned by visible light based on thionine
      bridged carbon nanotubes and gold nanoparticles multilayer.
AB  - A NADH and glucose biosensor based on thionine cross-linked multiwalled carbon
      nanotubes (MWNTs) and Au nanoparticles (Au NPs) multilayer functionalized indium
      doped tin oxide (ITO) electrode were presented in this paper. The effect of light
      irradiation on the enhancement of bioelectrocatalytic processes of the
      biocatalytic systems by the photovoltaic effect was investigated. This
      bioelectrode exhibited excellent catalytic activity of the oxidation towards
      dihydronicotinamide adenine dinucleotide (NADH). Most interesting, the
      performance of this NADH sensor could be tuned by the visible light. When the
      biosensor was performed in the dark, the anodic current increased linearly with
      NADH concentration over the range from 0.5 to 237 microM with detection limit 0.1
      microM and sensitivity 17 nA microM(-1). The sensitivity became 115 nA microM(-1)
      with detection limit 0.05 microM with the light irradiation. Compared with the
      reaction in dark, the sensitivity increased around 7 folds while the detection
      limit decreased 2 folds. The glucose biosensor also exhibited the same behavior.
      The linear range was from 10 microM to 2.56 mM with the sensitivity of 7.8
      microAmM(-1) and detection limit 5.0 microM in the dark. After the light
      irradiation, the linear range was from 1 microM to 3.25 mM with the sensitivity
      of 18.5 microA mM(-1) and detection limit 0.7 microM. It indicated a potential to
      provide an operational access to develop new kinds of photocontrolled
      dehydrogenase enzyme-based bioelectronics.

PMID- 18818068
TI  - Knowledge and understanding among cancer patients consenting to participate in
      clinical trials.
AB  - The aim of this study was to explore the fulfilment of the requirements of
      informed consent in patients participating in cancer clinical trials. All
      patients consenting to a phase II or III clinical trial during one year were
      included (n=325, 176 women, 54%). Data were collected by a questionnaire, Quality
      of Informed Consent. The response rate was 87%. High levels of knowledge (>80%)
      were found for items concerning voluntariness, randomisation, benefits for future
      patients, participation in a research trial, and the right to withdraw. Less than
      50% responded correctly to items about risks associated with the trial, the
      unproven nature of the trial and issues about insurances. High levels of
      perceived understanding were reported. Despite high levels of knowledge and
      perceived understanding in the majority of elements of informed consent,
      improvements are warranted regarding knowledge about risks, the unproven nature
      of the treatment and the duration of treatment.

PMID- 18818069
TI  - 2,4(5)-Diarylimidazoles: synthesis and biological evaluation of a new class of
      sodium channel blockers against hNa(v)1.2.
AB  - A small family of novel 2,4(5)-diarylimidazoles were prepared through a simple
      and efficient synthesis and evaluated as potential inhibitors of hNa(v)1.2 sodium
      channel currents. One member of this series (4) exhibited profound inhibition of
      Na(v)1.2 currents, emerging as a promising lead compound for further structure
      activity relationship studies for the development of novel sodium channel
      blockers.

PMID- 18818070
TI  - Discovery of small molecule agonists for the bombesin receptor subtype 3 (BRS-3)
      based on an omeprazole lead.
AB  - Starting from a weak omeprazole screening hit, replacement of the pyridine with a
      1,3-benzodioxole moiety, modification of the thioether linkage, and substitution
      of the benzimidazole pharmacophore led to the discovery of nanomolar BRS-3
      agonists.

PMID- 18818071
TI  - In vitro biological evaluation of novel 7-O-dialkylaminoalkyl cytotoxic
      pectolinarigenin derivatives against a panel of human cancer cell lines.
AB  - The effect of novel pectolinarigenin derivatives bearing a dialkylaminoalkyl
      substituent at O-7 on cell proliferation was evaluated in vitro in a panel of
      seven human cancer cell lines including renal adenocarcinoma ACHN, amelanotic
      melanoma C32, colorectal adenocarcinoma Caco-2, lung large cell carcinoma COR
      L23, malignant melanoma A375, lung carcinoma A549 and hepatocellular carcinoma
      Huh-7D12 cell lines. Pectolinarigenin (2), obtained by hydrolysis of rutinose
      unit of the pectolinarin (1) isolated from Linaria reflexa, exhibited cytotoxic
      activity against Caco-2, A549 and A375 cell lines with IC(50) values of 5.3-8.2
      microM. The most active pectolinarigenin derivative was 3 characterized by a
      dimethylamino-propoxy group in O-7 with IC(50) values of 7.2 and 7.4 microM
      against COR-L23 and A549 cell lines, respectively. A structure-activity
      relationship analysis of synthesized compounds was performed. None of the tested
      compounds affected the proliferation of skin fibroblasts 142BR suggesting a
      selective activity against tumor cells.

PMID- 18818072
TI  - Muscarinic acetylcholine receptor antagonists: SAR and optimization of tyrosine
      ureas.
AB  - SAR exploration of multiple regions of a tyrosine urea template led to the
      identification of very potent muscarinic acetylcholine receptor antagonists such
      as 10b with good subtype selectivity for M(3) over M(1). The structure-activity
      relationships (SAR) and optimization of the tyrosine urea series are described.

PMID- 18818073
TI  - Synthesis and in vitro biological evaluation of ring B abeo-sterols as novel
      inhibitors of Mycobacterium tuberculosis.
AB  - A series of 3beta-hydroxy steroid analogues possessing a contracted cyclopentane
      B-ring were prepared based on the initial activity screening of a recently
      reported naturally occurring marine 5(6-->7)abeo-sterol against Mycobacterium
      tuberculosis. All of the novel ring B abeo-sterols synthesized showed good
      inhibitory activity, whereas none of the starting steroids based on the common
      3beta-hydroxy-Delta(5)-cholestane nucleus, proved to be active. Therefore, the
      5(6-->7)abeo-sterol nucleus present in compounds 3, 5, 7, 9, and 11 represents a
      novel scaffold for the development of new antitubercular agents.

PMID- 18818074
TI  - Simplified YM-26734 inhibitors of secreted phospholipase A2 group IIA.
AB  - Simplified analogs of YM-26734, a known inhibitor of secreted phospholipase A(2)
      (sPLA(2)) group IIA, were synthesized and found to also display potent inhibition
      at low nanomolar concentrations. Analogs were based on the
      didodecanoylphloroglucinol portion of YM-26734 which contains the predicted
      active site calcium binding group.

PMID- 18818075
TI  - The identification of pyrazolo[1,5-a]pyridines as potent p38 kinase inhibitors.
AB  - A series of pyrazolo[1,5-a]pyridine derivatives was designed and synthesized as
      novel potent p38 kinase inhibitors. Our approaches towards improving in vitro
      metabolism and in vivo pharmacokinetic properties of the series are described.

PMID- 18818076
TI  - Towards harmonisation of outcome measures for DMD and SMA within TREAT-NMD;
      report of three expert workshops: TREAT-NMD/ENMC workshop on outcome measures,
      12th--13th May 2007, Naarden, The Netherlands; TREAT-NMD workshop on outcome
      measures in experimental trials for DMD, 30th June--1st July 2007, Naarden, The
      Netherlands; conjoint Institute of Myology TREAT-NMD meeting on physical activity
      monitoring in neuromuscular disorders, 11th July 2007, Paris, France.

PMID- 18818077
TI  - The relationship between regional body composition and quantitative strength in
      facioscapulohumeral muscular dystrophy (FSHD).
AB  - This study determines in facioscapulohumeral muscular dystrophy (FSHD) and able
      bodied controls (1) the regional body composition and (2) the correlation between
      regional lean tissue mass and the corresponding regional strength. This is a
      cross-sectional, criterion standard, case-control study at a university based
      neuromuscular disease clinic. A dual-energy X-ray absorptiometry (DEXA) scanner
      was used to obtain regional body composition measurements in 14 FSHD and
      anthropometrically matched control pairs. A dynamometer determined peak isometric
      strength for the elbow and knee. Compared to controls, FSHD subjects showed
      increased regional fat tissue mass (p < 0.001-0.017), decreased regional lean
      tissue mass (p < 0.001-0.010), and decreased strength (p < 0.001-0.020). There
      was a correlation between quantitative strength and lean tissue mass for both
      FSHD and controls (r = 0.791-0.906; p < 0.001). FSHD subjects have higher
      regional fat tissue mass and lower regional lean tissue mass despite similar BMI
      and anthropometrics. Regional lean tissue mass correlates with strength.

PMID- 18818078
TI  - Dystrophin knockdown mice suggest that early, transient dystrophin expression
      might be enough to prevent later pathology.

PMID- 18818079
TI  - Clinical and molecular overlap between myopathies and inherited connective tissue
      diseases.
AB  - This review presents an overview of myopathies and inherited connective tissue
      disorders that are caused by defects in or deficiencies of molecules within the
      extracellular matrix (ECM). We will cover the myopathies caused by defects in
      transmembrane protein complexes (dystroglycan, sarcoglycan, and integrins),
      laminin, and collagens (collagens VI, XIII, and XV). Clinical characteristics of
      several of these myopathies imply skin and joint features. We subsequently
      describe the inherited connective tissue disorders that are characterized by mild
      to moderate muscle involvement in addition to the dermal, vascular, or articular
      symptoms. These disorders are caused by defects of matrix-embedded ECM molecules
      that are also present within muscle (collagens I, III, V, IX, lysylhydroxylase,
      tenascin, fibrillin, fibulin, elastin, and perlecan). By focussing on the
      structure and function of these ECM molecules, we aim to point out the clinical
      and molecular overlap between the groups of disorders. We argue that clinicians
      and researchers dealing with myopathies and inherited connective tissue disorders
      should be aware of this overlap. Only a multi-disciplinary approach will allow
      full recognition of the wide variety of symptoms present in the spectrum of ECM
      defects, which has important implications for scientific research, diagnosis, and
      for the treatment of these disorders.

PMID- 18818080
TI  - Prefrontal neurons predict choices during an auditory same-different task.
AB  - The detection of stimuli is critical for an animal's survival [1]. However, it is
      not adaptive for an animal to respond automatically to every stimulus that is
      present in the environment [2-5]. Given that the prefrontal cortex (PFC) plays a
      key role in executive function [6-8], we hypothesized that PFC activity should be
      involved in context-dependent responses to uncommon stimuli. As a test of this
      hypothesis, monkeys participated in a same-different task, a variant of an
      oddball task [2]. During this task, a monkey heard multiple presentations of a
      "reference" stimulus that were followed by a "test" stimulus and reported whether
      these stimuli were the same or different. While they participated in this task,
      we recorded from neurons in the ventrolateral prefrontal cortex (vPFC; a cortical
      area involved in aspects of nonspatial auditory processing [9, 10]). We found
      that vPFC activity was correlated with the monkeys' choices. This finding
      demonstrates a direct link between single neurons and behavioral choices in the
      PFC on a nonspatial auditory task.

PMID- 18818081
TI  - Warts is required for PI3K-regulated growth arrest, autophagy, and autophagic
      cell death in Drosophila.
AB  - BACKGROUND: Cell growth arrest and autophagy are required for autophagic cell
      death in Drosophila. Maintenance of growth by expression of either activated Ras,
      Dp110, or Akt is sufficient to inhibit autophagy and cell death in Drosophila
      salivary glands, but the mechanism that controls growth arrest is unknown.
      Although the Warts (Wts) tumor suppressor is a critical regulator of tissue
      growth in animals, it is not clear how this signaling pathway controls cell
      growth. RESULTS: Here, we show that genes in the Wts pathway are required for
      salivary gland degradation and that wts mutants have defects in cell growth
      arrest, caspase activity, and autophagy. Expression of Atg1, a regulator of
      autophagy, in salivary glands is sufficient to rescue wts mutant salivary gland
      destruction. Surprisingly, expression of Yorkie (Yki) and Scalloped (Sd) in
      salivary glands fails to phenocopy wts mutants. By contrast, misexpression of the
      Yki target bantam was able to inhibit salivary gland cell death, even though
      mutations in bantam fail to suppress the wts mutant salivary gland-persistence
      phenotype. Significantly, wts mutant salivary glands possess altered
      phosphoinositide signaling, and decreased function of the class I PI3K-pathway
      genes chico and TOR suppressed wts defects in cell death. CONCLUSIONS: Although
      we have previously shown that salivary gland degradation requires genes in the
      Wts pathway, this study provides the first evidence that Wts influences
      autophagy. Our data indicate that the Wts-pathway components Yki, Sd, and bantam
      fail to function in salivary glands and that Wts regulates salivary gland cell
      death in a PI3K-dependent manner.

PMID- 18818082
TI  - 3' UTRs are the primary regulators of gene expression in the C. elegans germline.
AB  - How genes are regulated to produce the correct assortment of proteins for every
      cell type is a fundamental question in biology. For many genes, regulation begins
      at the DNA level with the use of promoter sequences to control transcription.
      Regulation can also occur after transcription using sequences in the 3'
      untranslated region (UTR) of the mRNA to affect mRNA stability and/or translation
      [1]. The C. elegans gonad is an excellent tissue to study gene regulation during
      development: In the adult, germ cells are arranged in order of differentiation,
      with undifferentiated progenitors at one end of the gonad, cells in meiotic
      prophase in the middle, and gametes at the other end [2]. Using a transgenic
      assay, we have compared the contribution of promoters and 3' UTRs to gene
      regulation during germline development. We find that for most genes tested, 3'
      UTRs are sufficient for regulation. With the exception of promoters activated
      during spermatogenesis, promoters are permissive for expression in all germ cell
      types (from progenitors to oocytes and sperm). In progenitors, 3' UTRs inhibit
      the production of meiotic and oocyte proteins by posttranscriptional mechanisms
      involving PUF- and KH-domain RNA-binding proteins. Our findings indicate that
      many genes rely primarily on 3' UTRs, not promoters, for regulation during
      germline development.

PMID- 18818083
TI  - Nontelomeric TRF2-REST interaction modulates neuronal gene silencing and fate of
      tumor and stem cells.
AB  - Removal of TRF2, a telomere shelterin protein, recapitulates key aspects of
      telomere attrition including the DNA-damage response and cell-cycle arrest [1].
      Distinct from the response of proliferating cells to loss of TRF2 [2, 3], in
      rodent noncycling cells, TRF2 inhibition promotes differentiation and growth [4,
      5]. However, the mechanism that couples telomere gene-silencing features [6-8] to
      differentiation programs has yet to be elucidated. Here we describe an
      extratelomeric function of TRF2 in the regulation of neuronal genes mediated by
      the interaction of TRF2 with repressor element 1-silencing transcription factor
      (REST), a master repressor of gene networks devoted to neuronal functions [9-12].
      TRF2-REST complexes are readily detected by coimmunoprecipitation assays and are
      localized to aggregated PML-nuclear bodies in undifferentiated pluripotent human
      NTera2 stem cells. Inhibition of TRF2, either by a dominant-negative mutant or by
      RNA interference, dissociates TRF2-REST complexes resulting in ubiquitin
      proteasomal degradation of REST. Consequentially, REST-targeted neural genes
      (L1CAM, beta3-tubulin, synaptophysin, and others) are derepressed, resulting in
      acquisition of neuronal phenotypes. Notably, selective damage to telomeres
      without affecting TRF2 levels causes neither REST degradation nor cell
      differentiation. Thus, in addition to protecting telomeres, TRF2 possesses a
      novel role in stabilization of REST thereby controlling neural tumor and stem
      cell fate.

PMID- 18818084
TI  - A self-regulating feed-forward circuit controlling C. elegans egg-laying
      behavior.
AB  - BACKGROUND: Egg laying in Caenorhabditis elegans has been well studied at the
      genetic and behavioral levels. However, the neural basis of egg-laying behavior
      is still not well understood; in particular, the roles of specific neurons and
      the functional nature of the synaptic connections in the egg-laying circuit
      remain uncharacterized. RESULTS: We have used in vivo neuroimaging and laser
      surgery to address these questions in intact, behaving animals. We have found
      that the HSN neurons play a central role in driving egg-laying behavior through
      direct excitation of the vulval muscles and VC motor neurons. The VC neurons play
      a dual role in the egg-laying circuit, exciting the vulval muscles while feedback
      inhibiting the HSNs. Interestingly, the HSNs are active in the absence of
      synaptic input, suggesting that egg laying may be controlled through modulation
      of autonomous HSN activity. Indeed, body touch appears to inhibit egg laying, in
      part by interfering with HSN calcium oscillations. CONCLUSIONS: The egg-laying
      motor circuit comprises a simple three-component system combining feed-forward
      excitation and feedback inhibition. This microcircuit motif is common in the C.
      elegans nervous system, as well as in the mammalian cortex; thus, understanding
      its functional properties in C. elegans may provide insight into its
      computational role in more complex brains.

PMID- 18818085
TI  - Kicking off the polo game.
AB  - Polo-like kinase 1 (Plk1) is essential for checkpoint recovery and the activation
      of key mitotic enzymes; however, its own activation mechanism has remained
      elusive. Recent findings show that Bora, a G(2)-M expressed protein, facilitates
      Plk1 activation by the oncogenic kinase Aurora A in G(2). During mitosis, Plk1
      dependent Bora degradation promotes Aurora A localization to the centrosome
      and/or spindle. Bora-dependent regulation provides important new insights into
      interactions between key mitotic kinases.

PMID- 18818086
TI  - Original preparation of conjugates for antibody production against Amicoumacin
      related anti-microbial agents.
AB  - Amicoumacins are natural products with potent anti-ulcerogenic and anti-bacterial
      activities, and have been isolated from different Bacillus genera. They belong to
      a family of 3,4-dihydroisocoumarin derivatives bearing hydroxylated amino acid
      side chains. The 3,4-dihydroisocoumarin moiety of Amicoumacins has been obtained
      in two steps from 2-methoxybenzoic acid by combining directed and benzylic
      metalation strategies. The use of s-BuLi in both steps gave satisfactory and
      reproducible yields. For the development of an immunoassay (ELISA) of Amicoumacin
      related compounds in biological media, the deprotected 3,4-dihydroisocoumarin
      moiety has been coupled to the BSA carrier protein via a homobifunctional linker
      deriving from d-tartaric acid. This approach enabled to introduce the
      hydroxylated portion of Amicoumacin directly during the preparation of hapten
      protein conjugates. The coupling ratio was evaluated by mass spectrometry. The
      hapten-protein conjugate showing the best coupling ratio was used to generate
      polyclonal immunosera in rabbits. After immunoserum titration, ELISA conditions
      were set up and specificity tests were performed on solutions of pure parent
      compounds, semi-purified Amicoumacin B as well as on culture supernatants of
      strains known for their Amicoumacin production. This immunoassay is suitable for
      a rapid and simple screening test for the production of Amicoumacins and its
      related compounds by bacterial strains.

PMID- 18818087
TI  - Synergistic effect of basic residues at positions 14-15 of nociceptin on binding
      affinity and receptor activation.
AB  - Nociceptin is an endogenous ligand that activates a G protein-coupled receptor
      ORL1 and contains two indispensable Arg-Lys (RK) dipeptide units at positions 8-9
      and 12-13. By replacing an additional RK unit at positions 6-7, 10-11, 14-15, or
      16-17, of the peptide we have identified the analog, [RK(14-15)]nociceptin as a
      superagonist. In fact, this peptide exhibits 3-fold higher binding affinity and
      17-fold greater potency in a functional GTPgammaS-binding assay compared to wild
      type nociceptin. Here, we have further investigated the role of basic residues in
      position 14-15. The replacement of three other possible basic dipeptides, KR, RR,
      and KK, into nociceptin at positions 14-15 resulted in similar enhancements of
      binding affinity (3-5-fold) and biological potency (10-12-fold in the GTPgammaS
      assay). However, when only a single basic residue (Arg or Lys) was replaced in
      either position 14 or 15, all the resulting analogs showed moderate enhancements
      of binding and biological activity (2-4-fold in both). These results indicate
      that the addition of basic charges in positions 14 and 15 enhance in a
      synergistic fashion the interaction of nociceptin with the receptor and only the
      simultaneous presence of two adjacent basic residues yields an optimal effect.
      This suggests that specific electrostatic interactions between both amino acids
      present in 14-15 and corresponding residues in the receptor are responsible for
      the enhancement of nociceptin activity.

PMID- 18818088
TI  - Novel potent inhibitors of A. thaliana cytokinin oxidase/dehydrogenase.
AB  - The synthesis of a new group of 2-X-6-anilinopurines, including compounds with
      potential cytokinin-like activities, with various substitutions (X=H, halogen,
      amino, methylthio or nitro) on the phenyl ring is described. The prepared
      compounds have been characterized using standard physico-chemical methods, and
      the influence of individual substituents on biological activity has been compared
      in three different bioassays, based on the stimulation of tobacco callus growth,
      retention of chlorophyll in excised wheat leaves and the dark induction of
      betacyanin synthesis in Amaranthus cotyledons. The biological activity of the
      prepared compounds was also assessed in receptor assays, in which the ability of
      the compounds to activate the cytokinin receptors AHK3 and AHK4/CRE1 was studied.
      Finally, the interactions of the compounds with the Arabidopsis cytokinin
      oxidase/dehydrogenase AtCKX2 (heterologously expressed) were investigated.
      Systematic testing led to the identification of two very potent inhibitors of
      AtCKX2: 2-chloro-6-(3-methoxyphenyl)aminopurine and 2-fluoro-6-(3
      methoxyphenyl)aminopurine.

PMID- 18818089
TI  - Synthesis and antitumoral evaluation of indole alkaloid analogues containing an
      hexahydropyrrolo[1',2',3':1,9a,9]imidazo[1,2-a]indole skeleton.
AB  - The scope of acid-mediated cyclative additions of electrophiles to tryptophan
      derived alpha-amino nitriles for the synthesis of 10b-substituted-1,2,4,5,10b,10c
      hexahydropyrrolo[1',2',3':1,9a,9]imidazo[1,2-a]indoles analogues of indole
      alkaloids has been studied. The results demonstrate the high potential of the
      methodology for the synthesis of 10b-bromo-derivatives, by bromination with NBS,
      10b-allyl-derivatives, by bromo-allyl exchange, and 10b-prenyl-derivatives, by
      reaction with prenyl bromide in the presence of Mg(NO(3))(2).6H(2)0. Some of the
      new pyrroloimidazoindole derivatives displayed moderate microM cytotoxicities in
      human cancer cell lines and at 10 microg/mL inhibited more than 50% EGFR or HIF
      1alpha.

PMID- 18818090
TI  - Structural basis for the recognition of methylated histone H3K36 by the Eaf3
      subunit of histone deacetylase complex Rpd3S.
AB  - Deacetylation of nucleosomes by the Rpd3S histone deacetylase along the path of
      transcribing RNA polymerase II regulates access to DNA, contributing to faithful
      gene transcription. The association of Rpd3S with chromatin requires its Eaf3
      subunit, which binds histone H3 methylated at lysine 36 (H3K36). Eaf3 is also
      part of NuA4 acetyltransferase that recognizes methylated H3K4. Here we show that
      Eaf3 in Saccharomyces cerevisiae contains a chromo barrel-related domain that
      binds methylated peptides, including H3K36 and H3K4, with low specificity and
      millimolar-range affinity. Nuclear magnetic resonance structure determination of
      Eaf3 bound to methylated H3K36 was accomplished by engineering a linked Eaf3
      H3K36 molecule with a chemically incorporated methyllysine analog. Our study
      uncovers the molecular details of Eaf3-methylated H3K36 complex formation, and
      suggests that, in the cell, Eaf3 can only function within a framework of
      combinatorial interactions. This work also provides a general method for
      structure determination of low-affinity protein complexes implicated in
      methyllysine recognition.

PMID- 18818091
TI  - Comparison of ALA- and ALA hexyl-ester-induced PpIX depth distribution in human
      skin carcinoma.
AB  - Photodynamic therapy (PDT) based on the use of photoactivable porphyrins, such as
      protoporphyrin IX (PpIX), induced by the topical application of amino-levulinic
      acid (ALA) or its derivatives, ALA methyl-ester (m-ALA), is a treatment for
      superficial basal cell carcinoma (BCC), with complete response rates of over 80%.
      However, in the case of deep, nodular-ulcerative lesions, the complete response
      rates are lower, possibly related to a lower bioavailability of PpIX. Previous in
      vitro skin permeation studies demonstrated an increased penetration of amino
      levulinic acid hexyl-ester (h-ALA) over ALA. In this study, we tested the
      validity of this approach in vivo on human BCCs. An emulsion containing 20% ALA
      (w/w) and preparations of h-ALA at different concentrations were applied
      topically to the normal skin of Caucasian volunteers to compare the PpIX
      fluorescence intensities with an optical fiber-based spectrofluorometer. In
      addition, the PpIX depth distribution and fluorescence intensity in 26 BCCs were
      investigated by fluorescence microscopy following topical application of 20% ALA
      and 1% h-ALA. We found that, for application times up to 24h, h-ALA is identical
      to ALA as a PpIX precursor with respect to PpIX fluorescence intensity, depth of
      penetration, and distribution in basal cell carcinoma, but has the added
      advantage that much smaller h-ALA concentrations can be used (up to a factor 13).
      We observed a non-homogenous distribution in BCCs with both precursors,
      independent of the histological type and depth of invasion in the dermis.

PMID- 18818092
TI  - A hierarchical algorithm for calculating the isotopic fine structures of
      molecules.
AB  - This article presents a memory efficient algorithm for accurately calculating the
      isotopic fine structures of molecules. Treating individual isotopic species of a
      molecule as different mass states, we introduce the concept of transitions
      between mass states and represent all mass states of the molecule in a
      hierarchical structure. We show that there exists a simple relationship between
      two different mass states at two different levels of the hierarchical structure.
      This allows us to efficiently and accurately compute both the mass and the
      abundance of every mass state of a small to medium-sized molecule, whose gross
      structures include small number of fine structures. A truncated calculation of
      this algorithm can be applied to calculate a majority of isotopic species (99.99%
      of cumulative abundance) of a large molecule.

PMID- 18818093
TI  - Bridging across the ampulla of Vater with covered self-expanding metallic stents:
      is it contraindicated when treating malignant gastroduodenal obstruction?
AB  - PURPOSE: To determine if concern for biliary obstruction constitutes a
      contraindication to the placement of a covered self-expandable metallic stent
      (SEMS) bridging the ampulla of Vater (AOV). MATERIALS AND METHODS: Retrospective
      review of fluoroscopic images of stent placement was performed in 62 patients (43
      men; mean age, 62 years) with malignant gastroduodenal obstruction treated with a
      partially covered SEMS. Bare (n = 35) and covered (n = 27) stent portions were
      placed to bridge the AOV. Preprocedural and postprocedural bilirubin and alkaline
      phosphatase (ALP) levels were reviewed. The incidence of external biliary
      drainage tube insertion within 1 month was compared between groups. In 27
      patients with postprocedural computed tomography studies, causes of bile duct
      dilation were evaluated. RESULTS: Compared to preprocedural data, postprocedural
      bilirubin and ALP levels were elevated significantly in both groups (bilirubin,
      mg/dL, 1.8 +/- 2.3 vs 2.8 +/- 3.7, P = .02 for bare, 1.6 +/- 1.7 vs 3.6 +/- 4.4,
      P = .02 for covered; ALP, IU/L, 193.2 +/- 174.8 vs 292.9 +/- 293.7, P = .01 for
      bare, 214.7 +/- 213.3 vs 357.6 +/- 234.4, P < .01 for covered group). Changes in
      laboratory measurements were not significantly different between groups
      (bilirubin, 1.1 mg/dL +/- 2.2 and 2.2 mg/dL +/- 4.0 in bare and covered groups,
      respectively [P = .19]; ALP, 128.9 IU/L +/- 207.0 and 156.3 IU/L +/- 136.1,
      respectively [P = .56]). The incidence of external biliary drainage tube
      insertion was not significantly different between groups (17.1% and 25.9% in bare
      and covered stent groups, P = .53). The stent was the cause of bile duct dilation
      in only one patient. CONCLUSIONS: It is suggested that it is not contraindicated
      to place a covered SEMS to bridge the AOV.

PMID- 18818094
TI  - Hepatocellular carcinoma: detection of blood supply from the right inferior
      phrenic artery by the use of multi-detector row CT.
AB  - PURPOSE: To evaluate retrospectively the ability of multi-detector row computed
      tomography (CT) to detect blood supply from the right inferior phrenic artery
      (RIPA) in patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS:
      Between July 2006 and June 2007, angiography of the RIPA was performed in 178
      patients (151 men, 27 women; mean age, 59 years) with HCC who also had undergone
      multi-detector row CT. CT scans and digital subtraction angiograms of these
      patients were retrospectively reviewed by consensus by two investigators to
      evaluate tumor feeder vessels. RESULTS: Tumor staining fed by the RIPA was noted
      on angiography in 113 patients (63%). Readers interpreted that the tumor feeder
      vessels were evident on CT images in 63 of these 113 patients (56%). Young age
      (odds ratio [OR], 0.934; P < .0001), exophytic growth pattern (OR, 2.702; P =
      .009), and presence of a visible feeder vessel on CT (OR, 6.933; P < .0001) were
      significant factors for predicting parasitic blood supply from the RIPA. In a
      subgroup of tumors smaller than 5 cm, multivariate analysis revealed that young
      age (OR, 0.94; P = .03) and repeated chemoembolization sessions (OR, 8.65; P =
      .01) were significant factors. CONCLUSIONS: Visualization of a tumor feeding
      vessel from the RIPA on multi-detector row CT could be a clue of a parasitic
      supply of a large tumor. In patients who have received repeated
      chemoembolization, small tumors in the dorsal hepatic area can be supplied by the
      RIPA.

PMID- 18818095
TI  - Pelvic pain after uterine artery embolization: a prospective randomized study of
      polyvinyl alcohol particles mixed with ketoprofen versus bland polyvinyl alcohol
      particles.
AB  - PURPOSE: To evaluate whether pelvic pain following uterine artery embolization
      (UAE) can be decreased by using ketoprofen mixed with polyvinyl alcohol (PVA).
      MATERIALS AND METHODS: A randomized prospective study was performed in 80
      patients (age range, 25-52 years; mean age, 41 years) undergoing UAE with PVA
      between March and August 2006. Forty patients received PVA particles mixed with
      ketoprofen, and 40 received bland PVA particles. Fifty-three patients who were
      asymptomatic 8 hours after embolization were discharged. Pain scores were
      compared during the first 8 hours after the procedure, at discharge, and the
      following day. The results were evaluated after 6 months. RESULTS: Eight hours
      after UAE, 13 of the 40 patients in the group without ketoprofen (32%) reported
      severe or very severe pain, whereas none of the patients in the group receiving
      ketoprofen reported severe or very severe pain, as determined with a numeric pain
      score scale (P = .0015). Nineteen of the 40 patients without ketoprofen (48%)
      were treated as inpatients, but only 10 in the ketoprofen group (25%) were
      treated as inpatients. The differences in the clinical outcome, as well in the
      uterus and fibroid sizes at discharge and at 6 months, were not statistically
      significant (P > .05). CONCLUSIONS: The use of PVA particles mixed with
      ketoprofen resulted in a statistically significant reduction in pelvic pain
      during the first 8 hours after UAE as compared to the use of PVA alone. However,
      no significant differences in pain scores were seen after 8 hours. These findings
      may lead to a reduction in inpatient management for UAE; however, further study
      of this approach is warranted.

PMID- 18818096
TI  - Biopsy of cardiac masses using a stabilized intracardiac echocardiography-guided
      system.
AB  - Biopsy of a cardiac mass remains a difficult and risky procedure. Successful
      sampling of target tissue is hampered by continuous cardiac motion and blood
      flow. Because the surrounding tissues are vascular, complications can include
      hemorrhage, tamponade, arrhythmia, embolization, and death. Conventional imaging
      modalities are of limited utility in this dynamic environment. The present report
      describes the use of the instrumentation system originally designed for creation
      of direct portocaval shunts with intracardiac echocardiography imaging to perform
      core biopsies of cardiac and juxtacardiac masses in six patients. There were no
      hemorrhagic complications, and pathologic diagnoses were obtained in five of six
      cases.

PMID- 18818098
TI  - Endovascular repair of traumatic mesocaval fistula.
AB  - A patient presented with a posttraumatic fistula between the superior mesenteric
      artery and inferior vena cava with associated pseudoaneurysm after multiple
      thoracoabdominal gunshot wounds. Endovascular management with placement of two
      overlapping stent-grafts resulted in complete resolution of the lesions with
      documented patency at 15 months and no known complications. This minimally
      invasive therapy spared the patient the morbidity of conventional open surgical
      repair.

PMID- 18818097
TI  - Four-dimensional transcatheter intraarterial perfusion MR imaging for monitoring
      chemoembolization of hepatocellular carcinoma: preliminary results.
AB  - PURPOSE: Angiographic endpoints for chemoembolization of hepatocellular carcinoma
      (HCC) are subjective, and optimal endpoints remain unknown. Transcatheter
      intraarterial perfusion (TRIP) magnetic resonance (MR) imaging, when performed in
      a combined MR/interventional radiology (MR-IR) suite, offers an objective method
      to quantify intraprocedural tumor perfusion changes, but was previously limited
      to two spatial dimensions. This study prospectively tested the hypothesis that a
      new volumetric acquisition over time, four-dimensional TRIP MR imaging, can
      measure HCC perfusion changes during chemoembolization. MATERIALS AND METHODS:
      Seven men (mean age, 53 years; range, 42-65 y) with eight tumors (mean size, 2.5
      x 2.4 cm(2); diameter range, 1.5-5.2 cm) underwent chemoembolization in an MR-IR
      suite between February and December 2007, with intraprocedural tumor perfusion
      reductions monitored with four-dimensional TRIP MR imaging. Microcatheter
      chemoembolization was performed with a 1:1 mixture of chemotherapy agent and
      emulsifying contrast agent, followed by the administration of gelatin
      microspheres. Pre- and post-chemoembolization time-intensity curves were
      generated for each tumor. Semiquantitative measures of tumor perfusion, including
      area under the curve (AUC), peak signal intensity (SI), time to peak SI, and
      maximum upslope (MUS), were calculated, and mean differences before and after
      chemoembolization were compared with paired t tests. RESULTS: Four-dimensional
      TRIP MR imaging-monitored chemoembolization was successful in all cases.
      Calculated AUCs before and after chemoembolization (439 vs 221, P = .004, 50%
      reduction), peak SI (32 vs 19, P = .012, 41% reduction), and MUS (11 vs 3, P =
      .028, 73% reduction) showed significant reductions after chemoembolization. Time
      to peak SI did not significantly change (23 sec vs 36 sec, P = .235, 57%
      increase). CONCLUSIONS: Four-dimensional TRIP MR imaging can successfully measure
      semiquantitative changes in HCC perfusion during MR-IR-monitored
      chemoembolization. Future studies may correlate changes in these objective
      functional parameters with tumor response.

PMID- 18818099
TI  - CT angiography of a gonadal artery collateral from an inferior accessory right
      renal artery.

PMID- 18818100
TI  - Mural thrombotic deposits in abdominal aortic endografts are common and do not
      require additional treatment at short-term and midterm follow-up.
AB  - PURPOSE: To assess the incidence and clinical significance of thrombotic,
      nonocclusive mural deposits in abdominal aortic stent-grafts incidentally found
      on follow-up computed tomography scans after endovascular aneurysm repair (EVAR).
      MATERIALS AND METHODS: Between 1998 and 2007, 288 patients underwent EVAR of an
      infrarenal aortic aneurysm. In the majority of cases, a Zenith stent-graft (n =
      187) or Excluder stent-graft (n = 71) was implanted. Clinical and radiologic
      follow-up was performed prospectively according to the EUROSTAR registry, with
      mean follow-up periods of 4.69 and 5.05 years, respectively, for the Excluder and
      Zenith groups. RESULTS: Thrombotic deposits were found in 17% and 33% of patients
      in the Excluder and Zenith groups, respectively, which represents a significant
      difference (P = .038). Clinically, no distal atheroembolic events were noted
      during follow-up, and there was no significant difference in survival between
      patients with and without thrombotic deposits (P = .80). CONCLUSIONS:
      Incidentally found thrombotic deposits in abdominal aortic endografts are common
      and device-specific, with a lower incidence in the Excluder group versus the
      Zenith group. These thrombotic deposits are clinically silent, do not require
      additional treatment at short-term and midterm follow-up, and do not affect the
      overall survival of the treated patients.

PMID- 18818101
TI  - Increased urinary orosomucoid excretion is not related to impaired renal function
      in patients with type 2 diabetes.
AB  - OBJECTIVES: Increased urinary orosomucoid excretion rate (UOER) independently
      predicted cardiovascular mortality in patients with type 2 diabetes at 5-years of
      follow-up. To further explore UOER in relation to local renal physiological
      phenomena, we studied renal glomerular and tubular functions in patients with
      type 2 diabetes and normal or increased UOER. METHODS: We performed a cross
      sectional study of 40 patients with type 2 diabetes (normal UOER, n=16; increased
      UOER, n=24) who displayed no signs of cardiovascular disease and 21 healthy
      control persons. The renal clearance values of [(51)Cr]ethylenediaminetetraacetic
      acid ([(51)Cr]EDTA), lithium, orosomucoid, albumin, and sodium were measured.
      RESULTS: Patients with type 2 diabetes had normal glomerular filtration rate
      (GFR) measured by [(51)Cr]EDTA clearance. The clearance value of orosomucoid was
      highly increased in patients with increased UOER. The clearance values of albumin
      were similar in patients with increased UOER and in healthy controls.
      Investigations of renal tubular function revealed normal and similar levels of
      lithium clearance and proximal and distal reabsorption of sodium and water. Serum
      values of orosomucoid were higher in patients with increased UOER than in healthy
      controls (P<.001), but were still within reference limits, suggesting chronic low
      grade inflammation. UOER was associated with increasing values of orosomucoid
      clearance (P<.0001) independently of serum orosomucoid. CONCLUSIONS: Patients
      with type 2 diabetes and increased UOER had normal GFR and showed no signs of
      renal glomerular or tubular dysfunction. We therefore hypothesize that increased
      levels of UOER may be caused by local renal production of orosomucoid due to
      chronic low-grade inflammation.

PMID- 18818102
TI  - Usefulness of concomitant biceps tenodesis in total shoulder arthroplasty: a
      prospective cohort study.
AB  - The purpose of this report is to assess the association of concomitant biceps
      tenodesis in total shoulder arthroplasty with treatment success 1 year after
      total shoulder arthroplasty. Of 136 consecutive shoulders (124 patients)
      undergoing primary total shoulder arthroplasty between 2003 and 2006, 54 (39.7%)
      underwent biceps tenodesis. For each patient, we obtained potential preoperative
      confounding data, such as age; gender; presence of rheumatoid arthritis; Short
      Form 36; number of previous shoulder operations; Disabilities of the Arm,
      Shoulder and Hand score; Shoulder Pain and Disability Index score; and insurance
      status. At the 1-year follow-up, we calculated the Constant score of all patients
      (ranging from 0 [worst] to 100 [best]). We first determined the crude association
      of concomitant biceps tenodesis with 1-year treatment success (Constant score >
      or =80) and then fitted a multivariate model correcting for potential confounders
      to assess the adjusted association of the biceps tenodesis on treatment success.
      The total number of treatment successes was 46 of 136 shoulders (33.8% of all
      prosthesis implantations). The crude association (odds ratio) of a concomitant
      biceps tenodesis with treatment success was 2.38 (95% confidence interval [CI]
      1.15 to 4.93; P = .02). When adjusting for potential confounders, we found that
      this association slightly increased to 2.97 (95% CI 1.00 to 8.85; P = .05).
      Concomitant biceps tenodesis appears to have a favorable effect on 1-year
      treatment success after total shoulder arthroplasty.

PMID- 18818103
TI  - A new arthroscopic classification of articular-sided supraspinatus footprint
      lesions: a prospective comparison with Snyder's and Ellman's classification.
AB  - The aim of this study was to find a descriptive rationale to quantify articular
      sided supraspinatus tendon tears in the transverse and coronal planes, leading to
      a 2-dimensional description of the tear pattern. Fifty-six consecutive patients
      with articular-sided, symptomatic supraspinatus tendon tears diagnosed clinically
      and by magnetic resonance imaging underwent standardized diagnostic arthroscopy.
      Intra-articular findings of the rotator cuff were classified according to Ellman
      and Snyder. In addition, the longitudinal tear was assessed according to the
      length of the peeled-off bony footprint in the coronal plane. The sagittal tear
      extension was defined as a tear of the lateral reflection pulley on the medial
      border of the supraspinatus tendon and/or a tear in the area of the crescent
      zone. Statistically, we found a high correlation (r = 0.920, P < .0001) between
      the classifications of Ellman and Snyder, and we found only a slight correlation
      between the classifications of Snyder and Ellman with this new classification.
      Neither the classification of Snyder nor that of Ellman reproduced the extension
      of the partial-thickness rotator cuff tear in the transverse and coronal planes
      related to its etiologic pathomorphology.

PMID- 18818104
TI  - Postictal psychosis: a retrospective study in patients with refractory temporal
      lobe epilepsy.
AB  - Postictal psychosis (PIP) represents 25% of the psychoses seen in epileptic
      patients. A high frequency of bilateral independent epileptiform activity has
      been observed in patients with PIP. The objective of this study was to determine
      the frequency of PIP in patients with temporal lobe epilepsy (TLE) who underwent
      video-EEG monitoring and to investigate possible differences between PIP and
      control patients. METHODS: Clinical, electroencephalographic and neuroimaging
      data of 5 PIP patients with TLE were compared with data of 50 patients with TLE
      without psychotic antecedents. Patients with a past history of interictal
      psychosis were excluded. RESULTS: From 55 patients, 5 were patients with PIP and
      50 controls. 31 (62%) were men, 9 (16.4%) had a previous history of encephalitis
      and 6 (10.9%) of status epilepticus. The mean age was 42.2 years (S.D. 12.93).
      Mean age at epilepsy onset was 16.95 years (S.D. 12.93) and mean seizure
      frequency 5seizures/month (S.D. 1.87). The frequency of PIP was 5/55 (9.1%).
      Previous history of status epilepticus was more frequent in PIP patients than in
      controls (p: 0.019). PIP patients more frequently had a non-lateralizing ictal
      EEG than controls (p: 0.001). Bitemporal lobe dysfunction revealed by
      neuropsychological studies was greater than expected by the observed lesion on
      MRI studies in patients with PIP. Moreover, the presurgical study was less
      conclusive in PIP than in control patients (p: 0.049). CONCLUSIONS: PIP is
      observed in up to 9% of patients with TLE undergoing video-EEG monitoring and
      most often develops in patients with bitemporal lobe dysfunction.

PMID- 18818105
TI  - The adaptor protein MITA links virus-sensing receptors to IRF3 transcription
      factor activation.
AB  - Viral infection triggers activation of transcription factors such as NF-kappaB
      and IRF3, which collaborate to induce type I interferons (IFNs) and elicit innate
      antiviral response. Here, we identified MITA as a critical mediator of virus
      triggered type I IFN signaling by expression cloning. Overexpression of MITA
      activated IRF3, whereas knockdown of MITA inhibited virus-triggered activation of
      IRF3, expression of type I IFNs, and cellular antiviral response. MITA was found
      to localize to the outer membrane of mitochondria and to be associated with VISA,
      a mitochondrial protein that acts as an adaptor in virus-triggered signaling.
      MITA also interacted with IRF3 and recruited the kinase TBK1 to the VISA
      associated complex. MITA was phosphorylated by TBK1, which is required for MITA
      mediated activation of IRF3. Our results suggest that MITA is a critical mediator
      of virus-triggered IRF3 activation and IFN expression and further demonstrate the
      importance of certain mitochondrial proteins in innate antiviral immunity.

PMID- 18818106
TI  - Clinical outcome of combined immunotherapy with interferon-alpha and low-dose
      interleukine-2 for Japanese patients with metastatic renal cell carcinoma.
AB  - The objective of this study was to retrospectively investigate clinical outcomes
      of combined immunotherapy with interferon-alpha (IFN-alpha) and low-dose
      interleukin-2 (IL-2) in Japanese patients with metastatic renal cell carcinoma
      (RCC). This study included a total of 52 patients with metastatic RCC who were
      treated by combined immunotherapy with IFN-alpha and low-dose IL-2 following
      radical nephrectomy. These patients received a subcutaneous injection of IFN
      alpha (5 to 6 million U/d) three times per week and intravenous injection of IL-2
      (1.4 million U/d) twice per week. Tumor response was evaluated every 16 weeks,
      and as a rule, this weekly regimen was repeated 50 times in patients with
      evidence of objective response or stable disease. In this series, complete
      response and partial response were achieved in 1 and 11 patients, respectively;
      however, the remaining 20 and 20 patients were diagnosed as showing stable
      disease and progressive disease, respectively. Of several parameters examined,
      presence of metastases at diagnosis and C-reactive protein (CRP) level were
      significantly associated with response to this combined therapy. The 1-, 3-, and
      5-year cancer-specific survival rates of these 52 patients were 80.4%, 51.7%, and
      38.8%, respectively. Furthermore, cancer-specific survival was significantly
      associated with performance status, presence of metastases at diagnosis,
      metastatic organ and CRP level on univariate analysis; however, only performance
      status and presence of metastases at diagnosis appeared to be independent
      predictors of cancer-specific death by multivariate analysis. Toxicities related
      to this therapy were generally mild and tolerable, limited to World Health
      Organization (WHO) grade 1 or 2 in the majority of patients. Collectively, these
      findings suggest that combined immunotherapy with IFN-alpha and low-dose IL-2
      could achieve comparatively acceptable oncological outcomes in patients with
      metastatic RCC; however, other therapeutic options should be considered in
      patients with unfavorable performance status and/or those positive for metastatic
      diseases at diagnosis.

PMID- 18818107
TI  - "Cancer stem cells"-lessons from Hercules to fight the Hydra.
AB  - Following the initial identification of hematopoietic tumor stem cells, such
      cells were also found in several solid tumor types. In urology, cancer stem cells
      have only been found in prostate tumors so far. The concept and detection of
      tumor stem cells rely heavily on findings derived from stem cell research.
      Therefore, in addition to identifying and characterizing urologic tumor stem
      cells, research in uro-oncology should also aim at better understanding the stem
      cell biology of urologic organs. Insights in similarities and differences gleaned
      from these studies could be used to develop strategies for targeted destruction
      of tumor stem cells while sparing the physiological stem cells. The main target
      of future curative therapies in uro-oncology must therefore be the central,
      immortal head of the Hydra, the tumor stem cell.

PMID- 18818108
TI  - Taxol synergizes with antioxidants in inhibiting hormal refractory prostate
      cancer cell growth.
AB  - Taxanes are chemotherapeutic agents commonly used to treat various carcinomas.
      Dietary antioxidants, such as vitamin E, green tea extracts, and isoflavones have
      been used against prostate cancer, and exhibit anticancer effects both in vitro
      and in vivo. We evaluated the combined effect of taxol (paclitaxel) with
      pyrrolidine dithiocarbamate, vitamin E, epigallocatechin gallate, and genistein
      in killing hormone-refractory prostate cancer cells. Those agents were tested on
      the hormone-refractory prostate cancer cell line PC-3, and the viability of the
      cells was determined using MTT {3 (4, 5-dimethylthiazo-2-yl)-2, 5-diphenyl
      tetrazolium} assay after drug treatment. PC-3 cells were sensitive to these drugs
      with 50% inhibitory concentrations of 0.1, 23, 220, 1122, and 260 microM, for
      taxol, pyrrolidine dithiocarbamate, epigallocatechin gallate, genistein, and
      vitamin E, respectively. Genistein, pyrrolidine dithiocarbamate, and
      epigallocatechin gallate showed synergistic cytotoxicity to PC-3 cells when
      combined with 0.01 microM taxol. Only high concentration of vitamin E showed a
      synergistic effect with this dose of taxol. Further study revealed that 3
      combinations could induce sub-G1 phase of cell cycle, induce apoptosis, and
      increase caspase activity and decrease Bcl-2 expression simultaneously. In
      conclusion, in addition to vitamin E, incorporation of these antioxidants with
      taxan-based cytotoxic therapies offers encouraging strategies for combating
      hormone-refractory prostate cancers.

PMID- 18818109
TI  - Differences in shotgun protein expression profile between superficial bladder
      transitional cell carcinoma and normal urothelium.
AB  - This study was undertaken to identify differences in protein expression profiles
      between superficial bladder transitional cell carcinoma (BTCC) and normal
      urothelial cells. We used laser capture microdissection (LCM) to harvest purified
      cells, and used two-dimensional liquid chromatography (2D-LC) followed by
      electrospray ionization-tandem mass spectrometry (ESI-MS/MS) to separate and
      identify the peptide mixture. A total of 440/438 proteins commonly appeared in 4
      paired specimens. Multi-step bioinformatic procedures were used for the analysis
      of identified proteins; 175/179 of the 293/287 proteins that were specific
      expressed in tumor/normal cells own gene ontology (GO) biological process
      annotation. Compared with the entire list of the international protein index
      (IPI), there are 52/46 GO terms exhibited as enriched and 6/10 exhibited as
      depleted, respectively. Significantly altered pathways between tumor and normal
      cells mainly include oxidative phosphorylation, focal adhesion, etc. Finally,
      descriptive statistics show that the shotgun proteomics strategy has practice
      directive significance for biomarker discovery by two-dimensional electrophoresis
      (2-DE) technology.

PMID- 18818110
TI  - Combined modality treatment with bladder preservation for muscle invasive bladder
      cancer.
AB  - OBJECTIVE: To evaluate the 5-year results of the following trimodal therapy for
      treatment of some selected cases of muscle invasive bladder cancer. MATERIALS AND
      METHODS: In this prospective study, we included 104 patients with transitional
      cell carcinoma (TCC) (T2 and T3a, N0, M0) who were amenable to complete
      transurethral resection. All patients received adjuvant chemo-radiotherapy (CRT)
      in the form of gemcitabine and cisplatin and conventional radiotherapy after the
      maximum resection of their tumors. Two weeks later, all cases had radiologic and
      cystoscopic evaluation. The patients who showed no evidence of the bladder tumors
      [complete response (CR)] went on to complete the CRT, while those with recurrent
      invasive tumors did not receive any more CRT and were assigned to have salvage
      cystectomy. Thereafter, all patients were subjected to a regular follow-up.
      RESULTS: This trimodal therapy was well tolerated in most of cases with no severe
      acute toxicities. Complete response was achieved in 78.8% of cases after the
      initial CRT, and tumor grade was found to be the most significant risk factor to
      predict this response (P = 0.004). With a median follow-up of 71 months for
      patients with initial CR, 16.2% of cases showed muscle invasive recurrences, and
      multifocality was the only significant risk factor for their development (P =
      0.003). Meanwhile, superficial recurrences were detected in 8.1% of cases with
      initial CR and were successfully treated with transurethral resection and
      intravesical bacillus Calmette-Guerin (BCG). On the other hand, we reported
      distant metastasis in 24.3% of patients with initial CR, and tumor grade, stage
      and multifocality were the most significant risk factors for this complication (P
      = 0.002, 0.031, 0.006). No cases of contracted bladder or late gastrointestinal
      complications were demonstrated in this series. The 5-year overall survival rate
      for patients with initial CR was 67.6%, and for all the patients in this study it
      was 59.4%. CONCLUSIONS: This trimodal therapy can be considered as a treatment
      option for patients with localized muscle invasive TCC. The best candidates for
      such therapy are those with solitary T2, low grade tumors that are amenable to
      complete transurethral resection.

PMID- 18818111
TI  - Endovascular treatment of aortic dissection: are we going into the right
      direction?

PMID- 18818112
TI  - Study of efficacy of miltefosine and allopurinol in dogs with leishmaniosis.
AB  - Visceral leishmaniosis is a life-threatening disease of medical, social and
      economic importance in endemic areas. It is an opportunistic infection in
      immunocompromised patients, including human immunodeficiency virus-positive
      subjects. Dogs are the main reservoir of Leishmania infantum. The aim of this
      study was to evaluate the efficacy of miltefosine and allopurinol for the control
      of human leishmaniosis using the dog as a model. The study included 28 sick dogs
      treated with miltefosine (2 mg/kg/day PO) administered concurrently with
      allopurinol (10 mg/kg/day, PO) for 30 days, and then with allopurinol alone, at
      the same dosage, for 1 year. Eight dogs (four of which relapsed) received a
      second cycle of miltefosine within 6 months of the first cycle. Efficacy was
      measured by real-time polymerase chain reaction assay on whole blood samples and
      lymph node aspirates, collected at baseline and every 3 months for 12 months. Of
      the total number of animals (28), two showed renal insufficiency and died after
      the start of therapy with miltefosine. Two other dogs presented some side effects
      to treatment, such as nausea, vomiting and reduction in white and red blood cell
      counts, and these animals were excluded from the follow-up. The results showed
      that the first cycle of therapy with miltefosine and allopurinol induced a
      drastic and progressive reduction of L. infantum load in lymph node aspirates but
      the second cycle did not eliminate the parasite.

PMID- 18818113
TI  - Kinesiophobia among physiological overusers with musculoskeletal pain.
AB  - BACKGROUND: Kinesiophobia has been established as an important factor among
      patients with musculoskeletal pain. Most research has been performed among
      patient groups described in terms of disuse. Little, however, is known about the
      impact of affective factors among patients with overuse injuries caused by
      exercise. AIM: The aims were to investigate the occurrence of kinesiophobia among
      patients with exercise induced pain (overuse group) as compared to a reference
      group (chronic low back pain, CLBP), and to investigate kinesiophobia in relation
      to the type of pain and levels of exercise in the overuse group. METHODS: All
      patients were referred with unspecific pain to the orthopaedic clinic in order to
      make a specific diagnosis. The overuse group consisted of 146 patients with
      exercise induced leg pain, and the reference group consisted of 154 patients with
      CLBP. All patients completed questionnaires regarding age, pain duration,
      severity of pain and subjective rating of kinesiophobia (TSK). The overuse group
      was subgrouped verified by an exercise test and diagnostic criteria and completed
      questionnaires about the level of exercise. RESULTS: More than 60% of the
      overusers presented with kinesiophobia, but they did not differ as compared to
      the reference group. No difference in kinesiophobia was found in the overuse
      subgroups divided after type of pain. The highest level of kinesiophobia was
      found among the non-exercisers. CONCLUSIONS: The results of this study point out
      the need for further elaborating on the concepts of use, overuse and disuse in
      relation to the fear-avoidance model.

PMID- 18818114
TI  - Cleidocranial dysplasia in a mother and her two children.
AB  - Cleidocranial dysplasia (CCD) is an autosomal dominant disease characterized by
      skeletal abnormalities which is secondary to haploinsufficiency of the
      transcription factor Runx2 that plays a role in osteoblast differentiation. In
      this report, we present a female patient who came to our Rheumatology outpatient
      clinic with widespread pain, who was diagnosed with fibromyalgia (FM), and who
      was investigated because of her phenotypic features together with her two
      children; and consequently, diagnosed with CCD. The diagnosis of CCD was
      confirmed with genetic analysis. The patient whose alkaline phosphatase was low
      had no osteoporosis on DEXA. It is unclear whether CCD has or does not have a
      causal relationship with widespread pain.

PMID- 18818115
TI  - [Axillary nerve schwannoma (case report)].
AB  - The schwannoma is a benign tumour that can be eradicated; it usually occurs in
      the peripheral nerves of the upper limb. We report an exceptional localization in
      the axillary nerve. The diagnosis is based on the typical MRI appearance: in
      addition, confirmation of the diagnosis has to be made by histological
      examination. The surgical treatment by resection, taking care to preserve
      adjacent nerve fibres. This allows recovery without any after-effects since the
      recurrence rate as well as the potential for malignant transformation of this
      type of tumour is low.

PMID- 18818116
TI  - [Double simultaneous fingertip metastasis of an epidermoid carcinoma. A case
      report].
AB  - Fingertip metastases are rare. The authors report the case of a patient with an
      epidermoid carcinoma of the larynx who presented with two separate finger pulp
      metastases in each hand. According to the literature this seems a very unusual
      occurrence. This diagnosis must be considered in the differential diagnosis of
      every suspicious fingertip lesion.

PMID- 18818117
TI  - Mechanisms of proteasome inhibitor action and resistance in cancer.
AB  - Proteasome inhibitors (PIs), such as bortezomib, carfilzomib or NPI-0052, have
      excellent clinical activity in patients with multiple myeloma and mantle cell
      lymphoma, and they are currently being evaluated in combination with other agents
      in patients with solid tumors. Although they exert broad effects on cancer cells,
      their ability to (1) stabilize pro-apoptotic members of the BCL-2 family, (2)
      inhibit the two major pathways leading to NFkappaB activation, and (3) cause the
      build-up of misfolded proteins appear to be particularly important. In addition,
      PIs may disrupt tumor-stromal interactions that drive NFkappaB activation and
      angiogenesis and in such a way sensitize cancer cells to other agents. Still,
      drug resistance ultimately emerges in all tumors that initially respond to PIs.
      This review provides an overview of the current thinking about how PIs may kill
      cancer cells exemplified for pancreatic cancer and the possible mechanisms
      involved in resistance to PIs.

PMID- 18818118
TI  - Laying down the bricks: logistic aspects of cell wall biosynthesis.
AB  - Plant cell wall polysaccharides are synthesised at the plasma membrane and in the
      Golgi apparatus. Current research efforts mainly try to address how these
      molecules are synthesised or modified. However, it is clear that polysaccharide
      synthesis in the two compartments needs to be carried out in a coordinated
      fashion, and that carbohydrates and proteins that are delivered from the Golgi to
      the cell surface have to undergo a range of modifications. Consequently, there
      appears to be a need for a fine-tuned system that coalesces signals from the
      wall, synthesis of carbohydrate-based molecules and vesicle shuttling. Several
      recent papers have scratched the surface for an initial understanding of these
      linked processes. For example, the impairment of the proton pumping activity in
      the trans-Golgi network, which is part of the cell's trafficking system, results
      in growth defects, changes in Golgi stack morphology and cellulose deficiency. An
      increased understanding of how cell wall synthesis is coordinated with the
      secretory machinery may facilitate avenues for modulating cell wall contents and
      therefore overall plant biomass.

PMID- 18818119
TI  - Study on the interaction of morphine chloride with deoxyribonucleic acid by
      fluorescence method.
AB  - The mode and mechanism of the interaction of morphine chloride, an important
      alkaloid compound to calf thymus deoxyribonucleic acid (ct DNA) was investigated
      from absorption and fluorescence titration techniques. Hypochromic effect was
      founded in the absorption spectra of morphine when concentration of DNA
      increased. The decreased fluorescence study revealed non-cooperative binding of
      the morphine to DNA with an affinity of 3.94x10(3)M(-1), and the stoichiometry of
      binding was characterized to be about one morphine molecule per nucleotide. Stern
      Volmer plots at different temperatures proved that the quenching mechanism was
      static. Ferrocyanide quenching study showed that the magnitude of K(SV) of the
      bound morphine was lower than that of the free one. In addition, it was found
      that ionic strength could affect the binding of morphine and DNA. Fluorescence
      polarization and denatured DNA studies also applied strong evidences that
      morphine molecule was partially intercalated between every alternate base pairs
      of ct DNA. As observed from above experiments, intercalation was well supported
      as the binding mode of morphine and ct DNA.

PMID- 18818120
TI  - Genetic analysis of West Nile virus isolates from US blood donors during 2002
      2005.
AB  - BACKGROUND: Since its introduction into North America in 1999, West Nile virus
      (WNV) has spread rapidly across United States (US). OBJECTIVE: To genetically
      analyze WNV isolates from US blood donors during 2002-2005. STUDY DESIGN: Full
      length nucleotide (NT) sequences of WNV isolates from 23 US volunteer blood
      donors of different geographic areas from 2002 to 2005 were determined and
      analyzed. RESULTS: Results indicated an overall lack of geographic pattern to WNV
      in US. Analyses of the viral genetic diversity demonstrated that the WNV evolved
      at approximately five NT substitutions and 0.8 amino acid (AA) mutations per
      genome per year. Comparison of the functional sequences of WNV genome showed a
      higher evolution rate in the coding region than in the non-coding region.
      Furthermore, a greater diversity was observed in the nonstructural proteins as
      compared to the structural proteins. Sequence alignment analysis revealed that
      the rapid spread of WNV in US was accompanied by the establishment of a dominant
      genetic variant with 11 conserved NT mutations. CONCLUSIONS: The establishment of
      a dominant genotype across US and the displacement and possible extinction of
      earlier progenitor genotypes appears to have resulted from the accumulation and
      fixation of 11 nucleotide mutations throughout the coding region of WNV genome.

PMID- 18818121
TI  - Brainstem encoding of voiced consonant--vowel stop syllables.
AB  - OBJECTIVE: The purpose of this study is to expand our understanding of how the
      human auditory brainstem encodes temporal and spectral acoustic cues in voiced
      stop consonant-vowel syllables. METHODS: Auditory evoked potentials measuring
      activity from the brainstem of 22 normal learning children were recorded to the
      voiced stop consonant syllables [ga], [da], and [ba]. Spectrotemporal information
      distinguishing these voiced consonant-vowel syllables is contained within the
      first few milliseconds of the burst and the formant transition to the vowel.
      Responses were compared across stimuli with respect to their temporal and
      spectral content. RESULTS: Brainstem response latencies change in a predictable
      manner in response to systematic alterations in a speech syllable indicating that
      the distinguishing acoustic cues are represented by neural response timing
      (synchrony). Spectral analyses of the responses show frequency distribution
      differences across stimuli (some of which appear to represent acoustic
      characteristics created by difference tones of the stimulus formants) indicating
      that neural phase-locking is also important for encoding these acoustic elements.
      CONCLUSIONS: Considered within the context of existing knowledge of brainstem
      encoding of speech-sound structure, these data are the beginning of a
      comprehensive delineation of how the human auditory brainstem encodes
      perceptually critical features of speech. SIGNIFICANCE: The results of this study
      could be used to determine how neural encoding is disrupted in the clinical
      populations for whom stop consonants pose particular perceptual challenges (e.g.,
      hearing impaired individuals and poor readers).

PMID- 18818122
TI  - Generation of the 40-Hz auditory steady-state response (ASSR) explained using
      convolution.
AB  - OBJECTIVE: In this study, the superposition theory of the 40-Hz auditory steady
      state response (ASSR) generation is investigated using auditory brainstem
      response (ABR) and middle latency responses (MLRs) obtained with 40 Hz jittered
      sequences with the continuous loop averaging deconvolution (CLAD) algorithm.
      METHODS: Click sequences at around 40 Hz with high (maximum length sequence),
      medium and low jitters were presented to normal hearing awake adult subjects
      monaurally. Overlapping MLR responses were deconvolved using the frequency domain
      CLAD method. In addition, conventional auditory MLRs at 4.88 Hz and ASSRs at 39.1
      Hz were obtained in all subjects. Synthetic ASSRs were constructed using
      different rate and jitter MLRs as base recordings. Contributions of the primary
      components were investigated by wave elimination using phasors. RESULTS: Findings
      indicate that the generation of the 40-Hz ASSRs can be explained successfully by
      the superposition of the ABR and MLR waves generated at that stimulation rate.
      N(a)-P(a) and N(b)-P(b) components of the MLR contribute about equally (45%
      each), while the wave V of the ABR contributes a lesser amount (10%).
      CONCLUSIONS: Forty-Hertz ASSRs are composite responses generated by the
      superposition of the major waves of the ABR and the MLR. Dramatic amplitude
      increase of the ASSR at 40Hz is primarily due to the superposition of the
      resonating P(b) component to the P(a) wave. SIGNIFICANCE: Several unexplained
      properties of the 40-Hz ASSR can be explained by the stimulus and brain state
      dependent characteristics of the slow ABR, the P(a) and the P(b) components of
      the MLR.

PMID- 18818123
TI  - Is ventilatory efficiency (VE/VCO(2) slope) associated with right ventricular
      oxidative metabolism in patients with congestive heart failure?
AB  - BACKGROUND: The relationship between minute ventilation and the rate of CO2
      elimination (VE/VCO2 slope) is associated with mortality in patients with
      congestive heart failure (CHF). The VE/VCO2 slope > or =34 denotes a poor
      prognosis and has been proposed to reflect abnormalities in pulmonary perfusion.
      AIMS: To study whether increased VE/VCO2 slope is associated with elevated right
      ventricular (RV) oxidative metabolism relative to the left ventricle (LV).
      METHODS: 21 patients with stable NYHA II-III CHF underwent symptom limited
      cardiopulmonary exercise testing. Dynamic [(11)C]acetate positron emission
      tomography (PET) was used to measure oxidative metabolism (k(mono)) of the LV and
      RV. Corrected RV oxidative metabolism (RVOx) was calculated as RV/LV k(mono)
      ratio. RESULTS: Peak VO2 was 16.2+/-4.1 ml/min/kg and the VE/VCO2 slope was
      33.4+/-6.1. LV and RV k(mono) were 0.046+/-0.009 and 0.037+/-0.007 min(-1),
      respectively, with a RVOx of 0.83+/-0.17. There was a good correlation between
      RVOx and the VE/VCO2 slope (r=0.61, p=0.0034). RVOx was 0.77+/-0.16 in patients
      with a VE/VCO2 slope <34 and 0.93+/-0.16 in patients with VE/VCO2 slope > or =34
      (p=0.047). CONCLUSION: RVOx correlates with VE/VCO2 slope in CHF patients. This
      supports the hypothesis that pulmonary vascular resistance is a determinant of
      the VE/VCO2 slope.

PMID- 18818124
TI  - Changes in tissue-Doppler echocardiographic assessment of left ventricular
      filling during NT-proBNP guided heart failure treatment titration: a pilot study.
AB  - BACKGROUND: Although brain natriuretic peptide (BNP) and E/Ea are closely related
      in heart failure (HF) patients and may be helpful to guide HF therapy, the
      response of E/Ea to changes in BNP over several weeks of intensive HF treatment
      optimisation is unknown. This study was designed to investigate this
      relationship. METHODS AND RESULTS: In 17 patients with decompensated HF,
      treatment was titrated to reduce the NT-proBNP level to <200pg/mL over 10 weeks.
      Paired NT-proBNP measurements and echocardiograms were performed at two weekly
      intervals during the study. Treatment titration was associated with a reduction
      in E/Ea (17.6+/-6.8S.D. to 13.7+/-5.0S.D., p=0.018) in keeping with the reduction
      in NT-proBNP (median 603 [S.E. 561] to 311 [S.E. 235], p=0.045). This
      relationship remained in those who responded to titration (reduction in NT-proBNP
      of >or=50%), and those who did not. The overall change in E/Ea was similar to the
      changes observed in NT-proBNP in each group however there appeared to be temporal
      differences in the changes in E/Ea and NT-proBNP. CONCLUSION: This pilot study
      demonstrates that the E/Ea decreases after NT-proBNP guided HF therapy. E/Ea may
      be a complementary target for HF therapy optimisation; this hypothesis should be
      further evaluated in larger scale randomised trials.

PMID- 18818125
TI  - HIV immunopathogenesis and strategies for intervention.
AB  - Therapeutic options aimed at tackling the HIV pandemic face many obstacles. The
      lack of readily accessible and affordable therapies means that most of those
      affected go untreated. The array of escape mechanisms used by HIV has undermined
      the efficiency of many antiviral products and continually represents a barrier to
      the development of an effective vaccine. Recent developments have seen a shift
      away from a cytopathic viral model of HIV pathogenesis towards the crucial role
      of immunopathogenic features--notably generalised immune activation--in the
      development of AIDS. As conventional vaccine strategies have sought to promote
      viral neutralisation and suppressive cellular responses, novel strategies that
      aim to address HIV immunopathogenesis should be sought. We review current opinion
      on HIV-induced pathogenic immune activation and strategies aimed at eliminating
      HIV, including a potential role for non-neutralising antibodies as part of a
      therapeutic vaccine option.

PMID- 18818126
TI  - Nerve sprouting suppresses myocardial I(to) and I(K1) channels and increases
      severity to ventricular fibrillation in rat.
AB  - Nerve sprouting in healed myocardial infarction has been associated with
      increased incidences of ventricular tachyarrhythmia and sudden cardiac death.
      However, the underlying electrophysiological mechanisms are unclear. To
      investigate the linkage between nerve sprouting and potassium channel function,
      we developed a rat model of cardiac sympathetic nerve sprouting by chronic
      subcutaneous injection of 4-methylcatechol, a potent stimulator of nerve growth
      factor (NGF) synthesis. Cardiac sympathetic nerves were visualized by
      immunohistochemical staining. Myocardial necrotic injury was created by focal
      cold shock across intact diaphragm to mimic infarction. Transient outward current
      (I(to)) and inward rectifier current (I(K1)) of cardiomyocytes were recorded with
      the whole-cell patch clamp technique. We found that chronic 4-MC administration
      1) increased cardiac NGF level and the density of cardiac sympathetic
      innervation; 2) decreased the expressions of Kv4.2, Kv channel-interacting
      protein 2 (KChIP2), Kir2.1, and the current densities of I(to) and I(K1); 3)
      reduced the phosphorylation of extracellular signal-regulated kinase 1/2
      (pERK1/2); and 4) decreased heart rate variability and increased the
      susceptibility to ventricular fibrillation. Myocardial necrotic injury exerted
      similar effects as 4-methylcatechol, and 4-methylcatechol plus myocardial
      necrotic injury intensified the cardiac effects of 4-methylcatechol alone and
      decreased the phosphoralation of cAMP response element-binding protein (CREB). We
      conclude that nerve sprouting suppressed the expressions and functions of
      myocardial I(to) and I(K1) channels and increased the susceptibility to
      ventricular fibrillation. These effects are associated with decreased
      phosphorylation of ERK and CREB and reduced expression of KChIP2.

PMID- 18818127
TI  - On the measurement of the functional properties of the CFTR.
AB  - A number of methods are currently employed to assess the functional properties of
      CFTR channels and their response to pharmacological potentiators, correction of
      the defective CFTR trafficking, and vectorial introduction of new proteins. Here
      we review the most common methods used to assess CFTR channel function. The
      suitability of each technique to various experimental conditions is discussed.

PMID- 18818128
TI  - High accuracy determination of malachite green and leucomalachite green in salmon
      tissue by exact matching isotope dilution mass spectrometry.
AB  - A high accuracy method for the quantification of malachite green (MG) and
      leucomalachite green (LMG) in salmon is described. Analytical challenges
      including the effects of analyte instability and matrix suppression were
      minimised by the use of exact matching isotope dilution mass spectrometry. The
      developed method included overnight extraction in acidified acetonitrile/ammonium
      acetate buffer and analysis by LC-MS/MS utilising isotopic internal standards.
      This method was used to determine the level of MG and LMG in a sample of salmon
      used in an international inter-comparison organised by the Comite Consultatif
      pour la Quantite de Matiere (CCQM). The sum of MG and LMG was found to be 9.32+/
      0.98ngg(-1) at the 95% confidence interval (relative expanded uncertainty 10.5%
      (k=2)). This encompassed the mean and median of the CCQM inter-comparison.

PMID- 18818129
TI  - Identification and significance of sterols in MSW landfill leachate.
AB  - The sterol content of leachate from two different landfills (labeled as landfill
      J and landfill R, respectively) at Wuhan, central China was examined by GC/MS.
      About 20 types of sterols were identified according to their mass spectra of TMS
      (trimethylsilyl derivates) ethers and their eluting orders. Three types of
      indices of sterols, namely the ratio of 5beta/(5beta+5alpha) stanol, the ratio of
      coprostanol/epicoprostanol and the ratio of coprostanol/cholesterol, were used to
      assess and cross-validate sterol sources. The results showed that landfill R
      suffered faecal pollution while there are complex sterol sources in landfill J.
      The ratios of cholesterol/(chloesterol+cholestanol) were 0.24 in landfill R and
      0.32 in landfill J, indicating cholesterol reduction in both landfills. C29
      sterols consisted of 58% of total sterols in landfill J leachate. The sources for
      the landfill leachate included not only allochthonous domestic wastes, but
      biodegradation products of autochthonous wastes in the landfills.

PMID- 18818130
TI  - A randomized, controlled trial of postoperative adjuvant cytokine-induced killer
      cells immunotherapy after radical resection of hepatocellular carcinoma.
AB  - BACKGROUND: With a resistance to conventional chemotherapy and radiotherapy,
      hepatocellular carcinoma has a high recurrence rate after radical resection.
      Adjuvant immunotherapy is a promising treatment for hepatocellular carcinoma.
      AIM: To evaluate the effect of adjuvant immunotherapy with cytokine-induced
      killer cells on the prognosis of hepatocellular carcinoma after radical
      resection. PATIENTS AND METHODS: From January 2000 to January 2002, we collected
      127 patients that met the selection criteria and randomly divided them into 3
      groups. After radical resection of the tumor, immunotherapy with cytokine-induced
      killer cells was performed for 3 courses in 41 patients (CIK-I group) and 6
      courses in 43 patients (CIK-II group). The other 43 patients received no
      postoperative adjuvant therapy (the control group). The 1-, 3-, and 5-year
      disease free survival rates and the overall survival were compared among the 3
      groups. RESULTS: The log-rank test showed that the disease-free survival rates
      were significantly higher in CIK-I group (p=0.001) and CIK-II group (p=0.004)
      than in the control group. No statistical significance was found between CIK-I
      group and CIK-II group (p=0.345). Cox regression suggested that treatment
      modality was a risk factor for recurrence. No statistical significance was found
      in the overall survival among the three groups. CONCLUSIONS: Postoperative
      immunotherapy with cytokine-induced killer cells may prevent
      recurrence/metastasis after radical resection of hepatocellular carcinoma.
      However, it cannot improve the overall survival.

PMID- 18818131
TI  - Effect of methylene blue on intra-abdominal adhesion formation in rats.
AB  - BACKGROUND: Adhesion formation represents an important clinical challenge in
      gastro-intestinal surgery. In the late era, methylene blue (MB) has been claimed
      to play a helping role in combating such a problem. In the present study, we
      investigated the effects of MB administered intraperitoneally on the surgically
      induced adhesions in rats and tried to clarify whether its impact is
      concentration-dependent. MATERIAL & METHODS: Seventy adult male Wistar rats were
      used. They were allocated into seven groups, ten rats each: one control, two sham
      operated and four experimental ones. Peritoneal adhesions were evoked by scraping
      the cecal serosa in the four experimental groups which were given different
      concentrations of MB, intraperitoneally. The animals of the control group were
      similarly dealt but were given saline. The rats of the sham-operated groups were
      given either MB or saline but without any serosal damage. RESULTS: After the
      elapse of two weeks, the resulting adhesions, inflammation and fibrosis were
      evaluated. In the rats treated with MB 1%, adhesions, inflammatory process and
      fibrosis scores were similar to those in the sham-operated rats and were
      significantly lower than those in all other groups. CONCLUSION: It could be
      concluded that MB, 1%, had the best anti-adhesion potential.

PMID- 18818132
TI  - [HANAC syndrome (hereditary angiopathy with nephropathy, aneurysms and muscle
      cramps) and mutations of the collagen 4A1 gene: a new basement membrane
      hereditary pathology with multisystemic expression].

PMID- 18818133
TI  - Extraskeletal Ewing sarcoma of the abdominal wall.
AB  - Ewing sarcoma is most commonly a bone tumour which has usually extended into the
      soft tissues at the time of diagnosis. Exceptionally, this tumour can have an
      extraskeletal origin. Clinical or imaging findings are non-specific and diagnosis
      is based on histology. We report a case of an extraskeletal Ewing sarcoma
      developed in the soft tissues of the abdominal wall in a 35-year-old woman who
      presented a painful abdominal wall tumefaction. Ultrasongraphy and computed
      tomography showed a large, well-defined soft tissue mass developed in the left
      anterolateral muscle group of the abdominal wall. Surgical biopsy was performed
      and an extraskeletal Ewing sarcoma was identified histologically.

PMID- 18818134
TI  - Current role of radionuclide imaging in differentiated thyroid cancer.
AB  - Nuclear medicine plays an integral role in the management of differentiated
      thyroid cancer. This editorial aims to provide a summary of the current role of
      radionuclide imaging, including whole body iodine scan and fluorodeoxyglucose
      (FDG)-positron emission tomography (PET), in the diagnostic work-up and follow-up
      of patients with thyroid cancer.

PMID- 18818135
TI  - The development of perioperative practices for liver transplantation: advances
      and current trends.
AB  - Transplantation is a young medical specialty that has grown rapidly over the past
      50 years. Anesthesiologists, surgeons and hepatologists are all essential
      partners in the process of determining patient outcome. Each specialty has made
      landmark improvements in patient outcome. However, there is still variability in
      practice patterns in each of the 3 major specialties. This review will use a
      historic perspective to explore the unique forces that shaped specific transplant
      practices and those that gave rise to differences in perioperative practices.
      Anesthesiologists and surgeons have made significant improvements in the
      management of blood loss, and coagulation monitoring and intervention. This has
      improved operative survival and early patient outcome. Perioperative survival has
      improved despite a worldwide shortage of donor organs and a trend to transplant
      sicker patients. A smaller pool of donor organs is required to meet the needs of
      an expanding waiting list. The innovations to reduce deaths on the transplant
      wait list are reviewed along with their impact on overall patient outcome. The
      evolving organ shortage is the pinnacle point in shaping future transplant
      practices. Currently, institutional-specific practices may be reinforced by the
      informal "tutorship" that is used to train physicians and by the resources
      available at each site of practice. However, there is evidence that specific
      intraoperative practices such as the use of a low central venous pressure,
      selection of vasopressors and certain surgical techniques can modify patient
      outcome. Further investigation is needed to determine whether the good or the bad
      associated with each practice prevails and in what unique circumstance.

PMID- 18818136
TI  - Pyogenic liver abscess associated with septic pulmonary embolism.
AB  - BACKGROUND: Septic pulmonary embolism (SPE) is one of the metastatic foci of
      pyogenic liver abscess. The purpose of this study was to investigate the clinical
      presentations of, and management options for patients with pyogenic liver abscess
      complicated with SPE. METHODS: A retrospective chart review was conducted from
      January 1, 1999 to December 31, 2005 inclusively, in a medical center in northern
      Taiwan. We collected and analyzed the clinical presentations, diagnostic
      modalities, treatment programs and prognoses for all pyogenic liver abscess
      patients with SPE. RESULTS: The association between liver abscess affected with
      the complication of SPE and diabetes mellitus was significant. There were 9
      patients who had pyogenic liver abscess with SPE. Abnormal chest radiograph (CXR)
      findings with multiple ill-defined peripheral round densities were noted in all
      patients. Seven patients were diabetic, fever occurred in 5 patients, respiratory
      symptoms were noted in 6 patients, and abdominal pain occurred in 3 patients.
      Endophthalmitis coexisted in 3 patients, meningitis in 1 patient, and necrotizing
      fasciitis in 2 patients. Microbiological studies revealed Klebsiella pneumoniae
      in 9 patients. Computed tomography (CT) demonstrated metastatic nodules in both
      lung lobes, some of which featured cavitation, in all 9 patients. Three patients
      soon advanced to acute respiratory failure, and later died due to acute
      respiratory distress syndrome and/or septic shock. The remaining 6 patients
      survived without complication during their hospital course. CONCLUSION: There is
      diagnostic value in performing a chest CT scan in diabetic patients who have
      liver abscess plus abnormal CXR findings with multiple ill-defined peripheral
      round densities, in order to detect SPE, which has a relatively poor outcome in
      patients with liver abscess.

PMID- 18818137
TI  - Diagnosis of prostate cancer: repeated transrectal prostate biopsy or
      transurethral resection.
AB  - BACKGROUND: Transrectal ultrasound-guided biopsy of the prostate is the major
      method by which prostate cancer is diagnosed. However, many patients might be
      overlooked with the initial biopsy. Not uncommonly, patients need repeated
      biopsies when they continue to exhibit suspicious clinical signs. This may cause
      psychological stress to both patients and doctors. The purpose of this study was
      to determine how many repeat transrectal biopsies are adequate for prostate
      cancer detection and when to switch to transurethral resection. METHODS: We
      retrospectively studied a cohort of 2,996 patients who had undergone prostate
      biopsy. If the biopsy specimen was negative for malignancy, patients were given
      the choice of either being managed with observation or undergoing transurethral
      resection of the prostate (TURP) if indicated. If there was a high suspicion of
      cancer, patients were advised to undergo additional biopsies. The primary
      endpoint of this study was a diagnosis of cancer. RESULTS: The cancer detection
      rate was 22.9% (685 of 2,996 patients) in specimens taken during the first
      transrectal biopsy, 8.7% in those taken during the second biopsy (32 of 336
      patients), and 6.1% in those taken during the third biopsy (6 of 98 patients).
      The cancer detection rate of TURP after 1 negative biopsy result was 9.3% (35 of
      375 patients), and that after 2 negative biopsy results was 17.1% (6 of 35
      patients). TURP-derived specimens that were pathologically diagnosed as malignant
      had lower Gleason grade on average, no matter how many repeat biopsies there were
      in patients whose previous transrectal biopsy specimens were negative for
      malignancy (p=0.002 for 2 negative biopsy results and p=0.007 for 3 negative
      biopsy results). CONCLUSION: The chance of detecting malignancy beyond a third
      transrectal biopsy procedure is low. TURP, therefore, might be an alternative
      procedure for obtaining tissue for pathologic diagnosis, especially in patients
      with rising prostate-specific antigen levels and comorbid illnesses such as
      obstructive symptoms.

PMID- 18818138
TI  - Multiple clinical manifestations and diagnostic challenges of incontinentia
      pigmenti--12 years' experience in 1 medical center.
AB  - BACKGROUND: Incontinentia pigmenti (IP) is a rare X-linked dominant disorder that
      involves ectodermal tissues of multiple systems. Previous reports are few in
      Taiwan. To contribute toward better understanding of IP, we describe and discuss
      the clinical features of cases that were diagnosed in a medical center during the
      past 12 years. METHODS: The medical records of all patients with IP between July
      1995 and June 2007 were reviewed retrospectively. The demographics, physical
      findings, pathology reports, molecular study reports, eosinophil counts and
      outcome were recorded. RESULTS: A total of 4 patients, 3 female and 1 male
      neonate, who met the criteria for the diagnosis of IP were enrolled. Among these
      cases, 3 were not diagnosed with IP at initial presentation but were regarded to
      have infectious diseases. A definite family history of 3 consecutive generations
      was proved not only by clinical manifestations but also by molecular study in 1
      patient. The patient also had retinal and vitreous body hemorrhage, which rapidly
      progressed to retinal detachment of the right eye in 2 months. Another patient
      presenting with stage III hyperpigmentation at birth had an extremely rare
      finding of left foot deformity. The male patient had unilateral and localized
      vesicular lesions over his left thigh. CONCLUSION: Diagnosis of IP is difficult
      in the neonatal period. Referral to experienced specialists is necessary.
      Multiple clinical characteristics of IP and rapid progression of ophthalmologic
      manifestations can be demonstrated through our study. Furthermore, 3 of the 4
      cases in our study are the very first reports in Taiwan.

PMID- 18818139
TI  - Primary tumor volume of nasopharyngeal carcinoma: significance for recurrence and
      survival.
AB  - BACKGROUND: Primary tumor volume (PTV) is known to be a significant prognostic
      factor in malignant tumor. There have been several studies of nasopharyngeal
      carcinoma (NPC) relating tumor volume to treatment outcome. Our study was
      designed to evaluate the effect of PTV on treatment outcomes in NPC treated with
      radiotherapy (RT)/concurrent chemoradiotherapy (CCRT) or CCRT with adjuvant
      chemotherapy. METHODS: We retrospectively reviewed 100 cases with newly diagnosed
      NPC who were treated with RT/CCRT or CCRT with adjuvant chemotherapy from 2002 to
      2006. Magnetic resonance imaging-derived PTV was calculated using the summation
      of-area technique. Kaplan-Meier plots and the log-rank test were used to estimate
      tumor recurrence (locoregional, distant, or both) and overall survival. Cox
      proportional hazards regression analysis was used to assess the prognostic impact
      of PTV. RESULTS: The median PTV was 12.94 mL. PTV remained an independent
      prognostic factor for distant metastasis (hazard ratio [HR], 1.04; p=0.03), for
      any relapse (HR, 1.04; p=0.02), and for overall survival (HR, 1.09; p<0.001) in
      multivariate analysis. In the large tumor volume group (PTV>15 mL), patients'
      metastasis-free survival rates, with and without adjuvant chemotherapy, were 100%
      and 68.3%, respectively (p=0.002). Their 3-year recurrence-free survival rates,
      with and without adjuvant chemotherapy, were 94.1% and 69.6%, respectively
      (p=0.006). In the small tumor volume group (PTV <or= 15 mL), this phenomenon was
      not observed. CONCLUSION: PTV had a close relationship with survival rates and
      recurrence rates in patients with NPC. The large tumor volume group (PTV>15 mL)
      was associated with more recurrence and poor survival rate, and it was suggested
      that these high-risk patients should benefit from CCRT followed by adjuvant
      chemotherapy.

PMID- 18818140
TI  - Visual impairment and falls in the elderly: the Shihpai Eye Study.
AB  - BACKGROUND: To investigate the association between visual impairment and falls in
      a metropolitan elderly Chinese population. METHODS: A population-based cross
      sectional study of eye diseases among subjects 65 years of age and older was
      conducted in the Shihpai community of Taipei between July 1, 1999 and December
      31, 2000. RESULTS: Of the 2,045 subjects invited, 1,361 (66.6%) participated in
      both the questionnaire and the eye examination. Sixty-two (4.6%; 95% confidence
      interval [CI], 3.4-5.7%) had experienced 2 or more falls in the previous 12
      months. On univariate analysis, best-corrected Snellen visual acuity of the
      better eye less than 6/12 (odds ratio [OR], 2.47; 95% CI, 1.18-5.18; p<0.001),
      female gender (OR, 2.52; 95% CI, 1.49-4.26; p<0.001), high waist-to-hip ratio
      (OR, 1.86; 95% CI, 1.00-3.47; p=0.01), history of diabetes mellitus (OR, 3.88;
      95% CI, 2.27-6.62; p<0.001) and cardiovascular disease (OR, 2.26; 95% CI, 1.34
      3.80; p=0.04) were significantly related to falls. In the final multiple logistic
      regression model controlling for other covariates, visual impairment (OR, 1.98;
      95% CI, 1.02-4.32; p<0.001), female gender (OR, 2.34; 95% CI, 1.29-4.23; p<0.01),
      history of diabetes (OR, 3.61; 95% CI, 2.03-6.40; p<0.01) and cardiovascular
      disease (OR, 1.96; 95% CI, 1.13-3.40; p=0.04) were significantly related to
      falls. CONCLUSION: Falls were significantly associated with a best-corrected
      Snellen visual acuity of less than 6/12.

PMID- 18818141
TI  - Chryseobacterium meningosepticum sepsis complicated with retroperitoneal hematoma
      and pleural effusion in a diabetic patient.
AB  - Intra-abdominal infection due to Chryseobacterium meningosepticum is rare, and
      bacteremia complicated with pleural effusion and retroperitoneal hematoma caused
      by C. meningosepticum has not been reported previously. A 57-year-old diabetic
      man presented with bacteremia with retroperitoneal abscess and pleural effusion
      caused by C. meningosepticum on the 12th day of hospitalization. His clinical
      condition improved after antimicrobial therapy with levofloxacin and rifampin,
      debridement of the retroperitoneal hematoma and left-side chest tube insertion.
      Antibiotics were administered for 1 month, and he was later transferred to a
      local respiratory care ward under afebrile condition. C. meningosepticum should
      be included in the list of suspected nosocomial infections, especially in
      patients with immunocompromised status. Administration of appropriate
      antibiotics, such as quinolone, minocycline, trimethoprim-sulfamethoxazole or
      rifampin, and treatment of local infection improve the clinical outcome of
      patients with C. meningosepticum infection.

PMID- 18818142
TI  - Infectious alopecia in a dog breeder after renal transplantation.
AB  - Tinea capitis rarely occurs in renal transplant recipients. We report this living
      related renal transplant patient receiving cyclosporine-based therapy who
      initially presented with severe exfoliation of the scalp with yellowish-white
      scales and marked hair loss. The lesions extended to the frontal area and both
      cheeks, resulting in several skin ulcers with perifocal erythematous inflammatory
      changes, and palpable cervical lymph nodes. A biopsy of a skin lesion revealed
      fungal infection and culture yielded Microsporum canis. The patient mentioned an
      outbreak of ringworm in her breeding dogs during this period. After adequate
      treatment of the patient and her infected animals with griseofulvin and
      disinfection of the environment, her skin lesions resolved dramatically, with
      regrowth of hair.

PMID- 18818143
TI  - Neonatal adrenal hemorrhage presenting as a multiloculated cystic mass.
AB  - Neonatal adrenal hemorrhage presenting as an abdominal mass in the newborn is not
      uncommon. However, judging the nature of a suprarenal mass is sometimes
      difficult, especially when the structure is more complex with unusual clinical
      course. We report a male newborn with neonatal adrenal hemorrhage presenting as a
      multiloculated cystic mass. The margins between the mass and left kidney were
      indistinct. All laboratory data including complete blood cell count, serum
      electrolytes, liver function, renal function, blood sugar, alpha-fetoprotein,
      beta-human chorionic gonadotropin, urinalysis, and 24-hour urine vanillylmandelic
      acid were within normal limits. Serial sonographic follow-up revealed failure to
      decrease in size without change in echogenicity. Surgical exploration was
      performed to exclude the possibility of malignancy. This case highlights the
      diagnostic problems that arise when a space-occupying lesion is found near or at
      the adrenal gland in the neonate. We suggest that early surgical intervention for
      the suprarenal mass without sufficient evidence of malignancy would not be
      prudent.

PMID- 18818144
TI  - Conditions associated with hypertension in a high-risk premature infant.
AB  - Hypertension is an uncommon but significant problem in high-risk neonates and
      infants, and the spectrum of potential causes is broad. Here, we describe an
      extremely premature infant (birth weight, 728 g; gestational age, 27 weeks) with
      multiple complications and hypertension. During admission, umbilical artery
      catheters were used for a period of time, and he suffered from respiratory
      distress syndrome, intraventricular hemorrhage, pulmonary hemorrhage, patent
      ductus arteriosus, pericardial effusion, heart failure, repeated sepsis, anemia,
      thrombocytopenia, chronic lung disease, and progressive liver damage. He was
      treated with multiple medications, including erythropoietin, indomethacin,
      epinephrine, dopamine, aminophylline, multiple antibiotics, amphotericin B, and
      total parenteral nutrition. Hypertension was first noted when he was 41 days old,
      with spontaneous remission. It then recurred, reaching higher than 100 mmHg when
      he was almost 4 months old. After stopping erythropoietin, hypertension subsided
      for a short period of time and went up again. Multiple factor-related
      hypertension in this premature infant was considered. Related literature on
      hypertension in premature infants is reviewed. In conclusion, multiple factors
      can influence blood pressure and may induce hypertension in high-risk premature
      infants. Thus, blood pressure should be closely monitored in high-risk premature
      infants. Judicious use of all medications and interventions are crucial to
      decrease the incidence of hypertension in high-risk premature infants.

PMID- 18818145
TI  - Ureterosciatic hernia causes obstructive uropathy.
AB  - Obstructive uropathy can be caused by urolithiasis, fibrotic ureteral stricture,
      inflammatory ureteritis with polyp formations, ureteral malignancy and various
      forms of external compression. Ureteral herniation is a relatively rare cause of
      obstructive uropathy and has been reported with herniation sites including
      inguinal canal, femoral canal and sciatic foramen. Most ureteral herniations
      occur in the inguinal area. In the literature, previous cases of sciatic ureter
      have been treated with observation in asymptomatic patients or with surgery in
      patients with obstructive uropathy or clinical symptomatology. We report the case
      of a 91-year-old female with asymptomatic hydronephrosis of the left kidney due
      to extremely rare ureterosciatic herniation. Her global renal function was
      acceptable. As she was elderly and a poor surgical candidate, watchful waiting
      was recommended after discussion with the patient and her family.

PMID- 18818146
TI  - Predation increases acoustic complexity in primate alarm calls.
AB  - According to most accounts, alarm calling in non-human primates is a biologically
      hardwired behaviour with signallers having little control over the acoustic
      structure of their calls. In this study, we compared the alarm calling behaviour
      of two adjacent populations of Diana monkeys at Tai forest (Ivory Coast) and
      Tiwai Island (Sierra Leone), which differ significantly in predation pressure. At
      Tai, monkeys regularly interact with two major predators, crowned eagles and
      leopards, while at Tiwai, monkeys are only hunted by crowned eagles. We monitored
      the alarm call responses of adult male Diana monkeys to acoustic predator models.
      We found no site-specific differences in the types of calls given to eagles,
      leopards and general disturbances, but there were consistent differences in how
      callers assembled calls into sequences. At Tiwai, males responded to leopards and
      general disturbances in the same way, while at Tai, males discriminated by giving
      call sequences that differed in the number of component calls. Responses to
      eagles were identical at both sites. We concluded that Diana monkeys are
      predisposed to use their repertoire in context-specific ways, but that
      ontogenetic experience determines how individual calls are assembled into
      meaningful sequences.

PMID- 18818147
TI  - Mathematical models of plant-soil interaction.
AB  - In this paper, we set out to illustrate and discuss how mathematical modelling
      could and should be applied to aid our understanding of plants and, in
      particular, plant-soil interactions. Our aim is to persuade members of both the
      biological and mathematical communities of the need to collaborate in developing
      quantitative mechanistic models. We believe that such models will lead to a more
      profound understanding of the fundamental science of plants and may help us with
      managing real-world problems such as food shortages and global warming. We start
      the paper by reviewing mathematical models that have been developed to describe
      nutrient and water uptake by a single root. We discuss briefly the mathematical
      techniques involved in analysing these models and present some of the analytical
      results of these models. Then, we describe how the information gained from the
      single-root scale models can be translated to root system and field scales. We
      discuss the advantages and disadvantages of different mathematical approaches and
      make a case that mechanistic rather than phenomenological models will in the end
      be more trustworthy. We also discuss the need for a considerable amount of effort
      on the fundamental mathematics of upscaling and homogenization methods
      specialized for branched networks such as roots. Finally, we discuss different
      future avenues of research and how we believe these should be approached so that
      in the long term it will be possible to develop a valid, quantitative whole-plant
      model.

PMID- 18818148
TI  - Facing future climate change: is the past relevant?
AB  - From a socio-economic perspective, the 'sharp end' of climate research is very
      much about looking forward in time. As far as possible, we need to know what to
      expect and approximately when to expect it. However, it is argued here that our
      approach to climate change (including its scientific basis and its policy
      implications) is firmly linked to our understanding of the past. This is mainly
      due to the role played by palaeoclimate reconstructions in shaping our
      expectations of the climate system, in particular via their ability to test the
      accuracy of our climate models. Importantly, this includes the intuitive models
      that each of us carries around in our mind, as well as the more complex numerical
      models hiding inside supercomputers. It is through such models that palaeoclimate
      insights may affect the scientific and political judgements that we must make in
      the face of persistent and ultimately irreducible predictive uncertainty. Already
      we can demonstrate a great deal of confidence in our current understanding of the
      global climate system based specifically on insights from the geological record.
      If further advances are to be made effectively, climate models should take
      advantage of both past and present constraints on their behaviour, and should be
      given added credence to the extent that they are compatible with an increasingly
      rich tapestry of past climatic phenomena. Furthermore, palaeoclimate data should
      be accompanied by clearly defined uncertainties, and organized in arrays that are
      capable of speaking directly to numerical models, and their limitations in
      particular.

PMID- 18818149
TI  - Between a rock and a hot place: the core-mantle boundary.
AB  - The boundary between the rocky mantle and iron core, almost 2900 km below the
      surface, is physically the most significant in the Earth's interior. It may be
      the terminus for subducted surface material, the source of mantle plumes and a
      control on the Earth's magnetic field. Its properties also have profound
      significance for the thermochemical and dynamic evolution of the solid Earth.
      Evidence from seismology shows that D'' (the lowermost few hundred kilometres of
      the mantle) has a variety of anomalous features. Understanding the origin of
      these observations requires an understanding of the elastic and deformation
      properties of the deep Earth minerals. Core-mantle boundary pressures and
      temperatures are achievable in the laboratory using diamond anvil cell (DAC)
      apparatus. Such experiments have led to the recent discovery of a new phase,
      'post-perovskite', which may explain many hitherto poorly understood properties
      of D''. Experimental work is also done using analogue minerals at lower pressures
      and temperatures; these circumvent some of the limits imposed by the small sample
      size allowed by the DAC. A considerable contribution also comes from theoretical
      methods that provide a wealth of otherwise unavailable information, as well as
      verification and refinement of experimental results. The future of the study of
      the lowermost mantle will involve the linking of the ever-improving seismic
      observations with predictions of material properties from theoretical and
      experimental mineral physics in a quantitative fashion, including simulations of
      the dynamics of the deep Earth. This has the potential to dispel much of the
      mystery that still surrounds this remote but important region.

PMID- 18818150
TI  - Volcanism and the atmosphere: the potential role of the atmosphere in unlocking
      the reactivity of volcanic emissions.
AB  - Recent measurements of reactive trace gas species in volcanic plumes have offered
      intriguing hints at the chemistry occurring in the hot environment at volcanic
      vents. This has led to the recognition that volcanic vents should be regarded not
      only as passive sources of volcanic gases to the atmosphere, but also as
      'reaction vessels' that unlock otherwise inert volcanic and atmospheric gas
      species. The atypical conditions created by the mixing of ambient atmosphere with
      the hot gases emitted from magma give rise to elevated concentrations of
      otherwise unexpected chemical compounds. Rapid cooling of this mixture allows
      these species to persist into the environment, with important consequences for
      gas plume chemistry and impacts. This paper discusses some examples of the
      implications of these high-temperature interactions in terms of nitrogen, halogen
      and sulphur chemistry, and their consequences in terms of the global fixed
      nitrogen budget, volcanically induced ozone destruction and particle fluxes to
      the atmosphere. Volcanically initiated atmospheric chemistry was likely to have
      been particularly important before biological (and latterly anthropogenic)
      processes started to dominate many geochemical cycles, with important
      consequences in terms of the evolution of the nitrogen cycle and the role of
      particles in modulating the Earth's climate.

PMID- 18818151
TI  - The atmospheric ocean: eddies and jets in the Antarctic Circumpolar Current.
AB  - Although the Antarctic Circumpolar Current (ACC) is the longest and the strongest
      oceanic current on the Earth and is the primary means of inter-basin exchange, it
      remains one of the most poorly represented components of global climate models.
      Accurately describing the circulation of the ACC is made difficult owing to the
      prominent role that mesoscale eddies and jets, oceanic equivalents of atmospheric
      storms and storm tracks, have in setting the density structure and transport
      properties of the current. The successes and limitations of different
      representations of eddy processes in models of the ACC are considered, with
      particular attention given to how the circulation responds to changes in wind
      forcing. The dynamics of energetic eddies and topographically steered jets may
      both temper and enhance the sensitivity of different aspects of the ACC's
      circulation to changes in climate.

PMID- 18818152
TI  - Introduction. Progress in Earth science and climate studies.
AB  - In this introductory paper, I review the 'visions of the future' articles
      prepared by top young scientists for the second of the two Christmas 2008
      Triennial Issues of Phil. Trans. R. Soc.A, devoted respectively to astronomy and
      Earth science. Topics covered in the Earth science issue include: trace gases in
      the atmosphere; dynamics of the Antarctic circumpolar current; a study of the
      boundary between the Earth's rocky mantle and its iron core; and two studies of
      volcanoes and their plumes. A final section devoted to ecology and climate
      covers: the mathematical modelling of plant-soil interactions; the effects of the
      boreal forests on the Earth's climate; the role of the past palaeoclimate in
      testing and calibrating today's numerical climate models; and the evaluation of
      these models including the quantification of their uncertainties.

PMID- 18818153
TI  - Should we believe model predictions of future climate change?
AB  - Predictions of future climate are based on elaborate numerical computer models.
      As computational capacity increases and better observations become available, one
      would expect the model predictions to become more reliable. However, are they
      really improving, and how do we know? This paper discusses how current climate
      models are evaluated, why and where scientists have confidence in their models,
      how uncertainty in predictions can be quantified, and why models often tend to
      converge on what we observe but not on what we predict. Furthermore, it outlines
      some strategies on how the climate modelling community may overcome some of the
      current deficiencies in the attempt to provide useful information to the public
      and policy-makers.

PMID- 18818154
TI  - International trends in nutritionally-related health and their implication for
      health policy.
AB  - To establish health policy which will be relevant and effectual for a decade or
      more, let alone the much longer term, is a challenging task for any period of
      human or planetary history. Presently it is more so than ever because of major
      demographic, economic, technological and scientific, climatic and territorial
      changes and uncertainties. There are various scenarios which might be envisaged
      for food-health relationships before global population size is expected to
      stabilize by about 2050, dependent on planetary health. These will reflect
      achieved food intakes which for many will not be optimal but realizable and food
      systems with varying degrees of safety, security and sustainability. Health
      patterns themselves are bound to continue to change from those associated with
      different levels of economic development to those which have more to do with
      locality, climate, education and equity. Every aspect of health is in some way
      intertwined with food and this will become more explicit. Decisions about food
      health relationships will take into account the United Nations MDGs (Millennium
      Development Goals), but be strongly influenced by technology, affordability,
      sustainability and ethics.

PMID- 18818155
TI  - How to define obesity? Evidence-based multiple action points for public
      awareness, screening, and treatment: an extension of Asian-Pacific
      recommendations.
AB  - Metabolic risks are greater in Asians than Caucasians at a given body mass index
      (BMI). It is generally accepted that the BMI cut-off points for defining
      overweight and obesity should be lower for Asians. However, the percent body fat
      at a given BMI and metabolic responses to fatness vary among the different ethnic
      groups in Asia. Therefore, roughly even-spaced multiple action points (i.e., BMIs
      of 23, 25, 27.5, 30, 32.5, 35 and 37.5) have been advocated for managing obesity
      in Asians. We propose here evidence-based ethnicity-specific action points for
      public awareness, screening, and treatment that take into consideration
      sensitivity, specificity, and positive/negative predictive values for
      cardiovascular disease and/or metabolic syndromes, which are the most preva-lent
      adverse consequences of obesity.

PMID- 18818156
TI  - Sociocultural factors relating to Tongans' and Indigenous Fijians' patterns of
      eating, physical activity and body size.
AB  - This paper reviews literature between 1974 and 2007 that addresses the impact of
      sociocultural factors on reported patterns of eating, physical activity
      (activity) and body size of Tongans and indigenous Fijians (Fijians) in their
      countries of origin. There have been changes in diet (more imported and fewer
      traditional foods), activity (reduced, especially in urban settings), residence
      (rural-urban shift) and body size (increased obesity and at a younger age). The
      prevalence of overweight/obesity in Tongans and Fijians has increased rapidly
      over the last two decades and remains among the highest in the world (>80% in
      Tonga; >40% in Fiji), with more females reported to be obese than males. The few
      studies that investigated sociocultural influences on patterns of eating,
      activity and/or body size in this population have examined the impact of
      hierarchical organisation, rank and status (sex, seniority), values (respect,
      care, co-operation) and/or role expectations. It is important to examine how
      sociocultural factors influence eating, activity and body size in order to i)
      establish factors that promote or protect against obesity, ii) inform culturally
      appropriate interventions to promote healthy lifestyles and body size, and iii)
      halt the obesity epidemic, especially in cultural groups with a high prevalence
      of obesity. There is an urgent need for more systematic investigations of key
      sociocultural factors, whilst taking into account the complex interplay between
      sociocultural factors, behaviours and other influences (historical;
      socioeconomic; policy; external global influences; physical environment).

PMID- 18818157
TI  - Levels of Omega 3 fatty acids in Australian seafood.
AB  - The aim of this study was to determine the quantity of omega 3 (n-3) fatty acids
      in commonly consumed species of South Australian fish. Omega 3 fatty acids ranged
      from 17.7% to 53.7% of total fat with docosahexaenoic acid (DHA, 22:6n-3) as the
      major omega 3 fatty acid in all 26 species tested (range 9.5 % to 47.1% of total
      fat). The levels of total omega 6 (n-6) fatty acids ranged from 2.3% to 20.2% of
      total lipids, chiefly as arachidonic acid (AA, 20:4n-6). Fatty fish such as
      Gemfish, Atlantic Salmon and Swordfish were found to be good sources of omega-3
      fatty acid (1360, 2252 and 2571 mg/100g fish respectively), while low fat fish
      such as Ling, Deep Sea Bream (Blue Warhou) and Blue Grenadier (0.5, 0.7 and 0.7%
      fat) had low levels of omega 3 fatty acid (222, 257 and 247 mg/100g). Because
      most white table fish consumed by Australians are so low in fat they are actually
      a limited source of omega 3 fats. The amount of fish required to be consumed to
      provide 1 g of omega 3 fatty acid per day ranged from 40 to 450 g.

PMID- 18818158
TI  - Determination of trans fatty acid levels by FTIR in processed foods in Australia.
AB  - Health authorities around the world advise 'limiting consumption of trans fatty
      acid', however in Australia the trans fatty acid (TFA) content is not required to
      be listed in the nutrition information panel unless a declaration or nutrient
      claim is made about fatty acids or cholesterol. Since there is limited knowledge
      about trans fatty acid levels in processed foods available in Australia, this
      study aimed to determine the levels of TFA in selected food items known to be
      sources of TFA from previously published studies. Food items (n=92) that contain
      vegetable oil and a total fat content greater than 5% were included. This
      criterion was used in conjunction with a review of similar studies where food
      items were found to contain high levels of trans fatty acids. Lipids were
      extracted using solvents. Gravimetric methods were used to determine total fat
      content and trans fatty acid levels were quantified by Attenuated Total
      Reflectance Fourier Transform Infrared spectroscopy. High levels of trans fatty
      acids were found in certain items in the Australian food supply, with a high
      degree of variability. Of the samples analysed, 13 contained greater than 1 g of
      trans fatty acids per serving size, the highest value was 8.1 g/serving. Apart
      from when the nutrition information panel states that the content is less than a
      designated low level, food labels sold in Australia do not indicate trans fatty
      acid levels. We suggested that health authorities seek ways to assist consumers
      to limit their intakes of trans fatty acids.

PMID- 18818159
TI  - Vitamin D intake and its food sources in Taiwanese.
AB  - In the early 20th Century, vitamin D was discovered and its Recommended Daily
      Allowance developed. However, average daily dietary intakes have not been
      reported until recently in the US. There are no food composi-tion and no intake
      data for vitamin D available in Taiwan. We have taken advantage of several
      population representative Nutrition and Health Surveys in Taiwan (NAHSIT)
      conducted from 1993 onwards of various age groups to examine this possibility
      systematically. Firstly, we collected and compiled the vitamin D content of foods
      from various sources to supplement the Taiwanese Food Composition Tables. Though
      these vitamin D data may not be fully representative of local food items, they
      serve as a reference point. Secondly, we have used the three NAHSITs databases,
      which all used the 24-hr recall method to collect dietary intake date and five
      food frequency questionnaire type questions to collect supplement data, to
      estimate most gender- and age-specific (in-clude: school children, adults and
      elderly) vitamin D intake from food source and supplements. Thirdly, we have
      defined the sources of vitamin D intake in Taiwanese (gender- and age-specific).
      Vitamin D intakes of Taiwanese were adequate except girls of high school and
      indigenous people. Fish and its products, milk, mushroom were the major vitamin D
      food sources. Supplement source vitamin D also varied greatly between age and gen
      der groups. Elderly women consumed almost 20% of vitamin D from supplements; 16
      18 years old boys consumed 2.47% vitamin D from supplements only.

PMID- 18818160
TI  - Consumption of purple sweet potato leaves decreases lipid peroxidation and DNA
      damage in humans.
AB  - Consumption of polyphenols is associated with reduced risk of chronic diseases,
      possibly via a variety of bio-mechanisms, including antioxidation and anti
      inflammation. Purple sweet potato leaves (PSPL) commonly consumed in Asia possess
      polyphenols. In this study, we aim to investigate antioxidant effect of 200 g/d
      PSPL containing 902 mg polyphenols in a clinical trial. This randomized,
      crossover clinical study included 16 healthy adults (7 M, 9 F; aged 20-22 y).
      After a 1-wk run period, subjects were assigned randomly to receive either PSPL
      or low polyphenol diet (LPD) for 2 wks, followed by a 2-wk washout period before
      crossing over to the alternate diet. Fasting blood and 24-h urine samples were
      collected from each subject at day 0, 7 and 14 of each phase. Our data showed
      PSPL consumption enhanced urinary total phenol excretion by 24.5% at day 14 as
      compared to day 0, while the LPD decreased total phenol content in plasma and
      urine by 3.3 and 16.3%, respectively (p< or =0.05). Low-density lipoprotein lag
      time and glutathione concentration in erythrocytes at day 14 was significantly
      enhanced by 15.0 and 33.3% by PSPL as compared to day 0, respectively, while
      their values were not altered by the LPD. Urinary 8-hydoxy-deoxyguanosine (8
      OHdG) excretion decreased significantly by PSPL consumptoin by 36.7% at day 7 as
      compared to day 0, yet unchanged by the LPD (p< or =0.05). In conclusion, our
      results suggest that polyphenols in 200 g PSPL were bioavailable and could
      enhance antioxidant defense and decrease oxidative stress in young healthy
      people.

PMID- 18818161
TI  - Effect of diacylglycerol on body weight: a meta-analysis.
AB  - The effects of diacylglycerol (DAG) on body weight are not consistent in clinical
      trials. This meta-analysis of randomized controlled trials was conducted to
      evaluate the efficacy of dietary DAG on body weight. Potential articles were
      initially searched from the electronic databases of Medline, Embase and Cochrane
      library using the subject keywords as follows: weight, DAG, triacylglycerol
      (TAG), reduction and obesity. Inclusion criteria required the trial to be
      randomized placebo controlled with body weight as an endpoint. Two reviewers
      independently extracted the information and evaluated the methodological quality
      using the scoring system developed by Jadad. Meta-analysis was performed with the
      software of Review Manager 4.2. The robustness of overall analysis was tested by
      sensitivity analysis and publication bias was visually inspected by funnel plot.
      Five published trials were included in the statistical pool. The meta-analysis
      indicated a significant difference in body weight reduction between group
      receiving DAG and group receiving TAG (weighted mean difference -0.75 kg; 95% CI:
      -1.11 to -0.39; p < 0.0001). Sensitivity analysis corroborated the result of the
      overall analysis. Linear regression analysis showed that there was significant
      correlation between daily dose and body weight reduction (p = 0.044, R2 = 0.889).
      In conclusion, this meta-analysis suggested that DAG was efficacious for reducing
      body weight compared with TAG and this effect was influenced by the daily dose.

PMID- 18818162
TI  - Waist circumference percentile criteria for the pediatric metabolic syndrome in
      Korean adolescents.
AB  - This study aimed to determine valid waist circumference (WC) thresholds using
      receiver operating characteristic (ROC) curves for pediatric metabolic syndrome
      (MS) prediction and to compare validities between the thresholds derived from ROC
      curves and the WC cut-offs defined by International Diabetes Federation (IDF).
      Four hundred and sixty four males and 415 females, 10-18 years, who participated
      in the KNHNES 2005 were included. Subjects were classified as having pediatric MS
      when a high WC and > or = 2 of the risk factors defined by IDF were present. High
      WC was defined using either IDF criterion (> or =90th percentile for age and sex
      specific WC based on Korean reference in adolescents 10-15 years of age, > or
      =90cm in males and > or =80cm in females 16-18 years of age) or age-adjusted WC
      thresholds derived from the ROC curves predicting > or = 2 abnormal risk factors.
      The AUCs were 0.71-0.81 (sensitivity 74-100%, specificity 52-65%) among males and
      0.63-0.76 (sensitivity 71-90%, specificity 37-87%) among females for WC
      thresholds (55th and 32th percentile for males and females 10-15 years of age,
      73cm and 76cm for males and females 16-18 years of age), while the AUCs were 0.65
      0.66 (sensitivity 39-45%, specificity 84-93%) among males and 0.53-0.76
      (sensitivity 20-57%, specificity 86-96%) among females for IDF-defined WC cut
      offs. The prevalence of MS using IDF definition for WC was 4% in males and 2% in
      females, while those using WC thresholds were 8% and 5%, respectively. The IDF's
      definition of abdominal obesity may be less sensitive in screening adolescents
      with pediatric MS compared to WC thresholds.

PMID- 18818163
TI  - Multiple micronutrient deficiencies persist during early childhood in Mongolia.
AB  - Data on the prevalence of micronutrient deficiencies in children in Mongolia is
      limited. We therefore determined the prevalence of anaemia, iron deficiency
      anaemia (IDA), and deficiencies of iron, folate, vitamin A, zinc, selenium, and
      vitamin D among young Mongolian children. Anthropometry and non-fasting morning
      blood samples were collected from 243 children aged 6-36 months from 4 districts
      in Ulaanbaatar and 4 rural capitols for haemoglobin (Hb), serum ferritin, folate,
      retinol, zinc, selenium, and 25-hydroxyvitamin D (25-OHD) assays. Children with
      alpha-1-glycoprotein >1.2mg/L (n=27) indicative of chronic infection were
      excluded, except for folate, selenium, and 25-hydroxyvitamin D assays. Of the
      children 14.5% were stunted and none were wasted. Zn deficiency (serum Zn <9.9
      micromol/L) had the highest prevalence (74%), followed by vitamin D deficiency
      61% (serum 25-OHD<25 nmol/L). The prevalence of anaemia (24%) and iron deficiency
      anaemia (IDA) (16%) was lower, with the oldest children (24-36 mos) at lowest
      risk. Twenty one percent of the children had low iron stores, and 33% had vitamin
      A deficiencies (serum retinol < 0.70 micromol/L), even though two thirds had
      received vitamin A supplements. Serum selenium values were low, perhaps
      associated with low soil selenium concentrations. In contrast, no children in
      Ulaanbaatar and only 4% in the provincial capitols had low serum folate values
      (<6.8 nmol/L). Regional differences (p<0.05) existed for anaemia, deficiencies of
      vitamin A, folate, and selenium, but not for zinc or IDA. Of the children, 78%
      were at risk of > or = two coexisting micronutrient deficiencies emphasizing the
      need for multimicronutrient interventions in Mongolia.

PMID- 18818164
TI  - Calcium, magnesium, potassium and sodium intakes in Japanese children aged 3 to 5
      years.
AB  - The present study aimed to evaluate in preschool children the intakes of Ca, Mg
      that possibly affect health and tooth formation and the intakes of K and Na that
      may affect lifestyle-related diseases. Information on dietary intake was
      collected from 90 preschool children (15 boys and 15 girls each in the 3-, 4- and
      5-year old groups) on 3 separate days in the school fiscal year 1999 (April 1999
      to March 2000) by the duplicate-diet technique. The Ca, Mg, K, and Na
      concentrations were determined by atomic absorption spectrometry using wet-ashed
      samples. The medians of mean daily intakes of Ca, Mg, K and Na in 3- to 5-year
      old children were 432 mg, 110 mg, 1.18 g and 1.60 g, respectively, and no
      significant differences with regard to gender were observed. Seasonal varia-tion
      of intake was seen for each mineral. Calcium intake in most preschool children
      did not meet adequate intake (AI), probably due to low intakes of milk and dairy
      products in Japan. Magnesium intake was below the estimated average requirement
      (EAR) in 13.3% of the subjects, while the K intake met the AI. Sodium intake in a
      quarter of preschool children exceeded the tentative dietary goal. We concluded
      that in Japanese children aged 3-5 years; Ca intake is low, Na intake is high,
      and K intake is adequate, but some children could be at risk for Mg deficiency.

PMID- 18818165
TI  - Vitamin A supplementation in Cambodia: program coverage and association with
      greater maternal formal education.
AB  - Vitamin A supplementation reduces morbidity, mortality, and blindness among
      children in developing countries. The objective of this study is to characterize
      the coverage of the Cambodian national vitamin A program among preschool children
      and to identify risk factors for not receiving vitamin A supplementation. The
      study subjects were preschool children and their families who participated in the
      2005 Cambodian Demographic and Health Survey (CDHS), a nationally representative
      survey. Of 1,547 preschool children, aged 12-59 months, 42.8% received a vitamin
      A capsule within the last six months. There were no significant differences in
      paternal education, child age, fever within the last 2 weeks, stunting,
      underweight, or wasting between children who did or did not receive a vitamin A
      capsule. Maternal education of > or =10 years (Odds Ratio [OR] 2.09, 95%
      Confidence Interval [CI] 1.02-4.29), 7-9 years (OR 1.46, 95% CI 0.99-2.15), 4-6
      years (OR 1.71, 95% CI 1.26-2.32), and 1-3 years (OR 1.50, 95% CI 1.10-2.06) was
      associated with the child receiving a vitamin A capsule compared to no formal
      education in multivariate analyses adjusting for other potential confounders. The
      national vitamin A supplementation program in Cambodia did not reach over one
      half of preschool children in 2005. Greater maternal formal education appears to
      be an important determinant for receipt of a vitamin A capsule by preschool
      children.

PMID- 18818166
TI  - Hepcidin and iron status among pregnant women in Bangladesh.
AB  - Although hepcidin, a recently discovered peptide hormone, is considered a major
      regulator of iron metabolism and anemia in chronic inflammation, its role in
      anemia during pregnancy has not been characterized. Our objective was to
      characterize the role of hepcidin in anemia during pregnancy. We examined the
      relationships between urinary hepcidin, iron status indicators, hemoglobin,
      erythropoietin, alpha-1 acid glycoprotein, and C-reactive protein in a cross
      sectional study conducted among 149 pregnant rural Bangladeshi women with
      biospecimens obtained during home visits. Urinary hepcidin was measured using
      surface-enhanced laser desorption/ ionization time-of-flight mass spectrometry.
      Urinary hepcidin, as log(intensity per mmol/L creatinine), was correlated with
      log ferritin (r = 0.33, p <0.001), the transferrin receptor index (r = -0.22, p =
      0.007), and log alpha-1 acid glycoprotein (r = 0.20, p = 0.01), but not
      hemoglobin (r = 0.07, p= 0.40), log transferrin receptor (r = -0.07, p = 0.41),
      log erythropoietin (r = -0.01, p = 0.88) or log C-reactive protein (r = 0.06, p =
      0.48). The strength of the relationship between hepcidin and ferritin was
      maintained in multiple linear regression analyses after enhancing the sample with
      data from women selected for low iron stores (n = 41). Among pregnant women in a
      community-based study in rural Bangladesh, urinary hepcidin levels were related
      to iron status and AGP but not hemoglobin, erythropoietin, or C-reactive protein.

PMID- 18818167
TI  - Body shape dissatisfaction and obesity among Taiwanese adolescents.
AB  - PURPOSE: The purpose of this study was to estimate the level of body shape
      dissatisfaction among a large sample of adolescent boys and girls within
      different weight categories. METHODS: A total sample of 883 adolescents aged 12
      to 16 was included from junior high schools in Taipei County, Taiwan. The Contour
      Drawing Rating Scale was used to assess body shape dissatisfaction. RESULTS: Body
      shape dissatisfaction is prevalent in Taiwanese adolescents, particularly for
      girls. This is linked to degree of overweight in both boys and girls but is also
      prevalent in girls who are not overweight or obese. Girls and boys clearly aspire
      to thinness but some boys would also prefer to be larger. CONCLUSIONS: This study
      extends our understanding of body shape dissatisfaction and its relationship with
      weight status in eastern cultures such as Taiwan.

PMID- 18818168
TI  - High fish consumption in French Polynesia and prenatal exposure to metals and
      nutrients.
AB  - French Polynesians consume high quantities of fish and are therefore exposed to
      seafood-related contaminants such as mercury (Hg) or lead (Pb) and nutrients such
      as iodine, selenium and long chain polyunsaturated fatty acids (LC-PUFAs). As the
      developing foetus is sensitive to contaminants and nutrients, a cross-sectional
      study was conducted in French Polynesia in 2005-2006 to assess prenatal exposure
      to contaminants and nutrients through fish consumption. Two hundred and forty one
      (241) delivering women originating from all islands of French Polynesia were
      recruited and agreed to answer questions on fish consumption and gave permission
      to collect umbilical cord blood for metals and nutrients analyses. All parameters
      were found in high concentrations in cord blood samples except for lead. Mercury
      concentrations averaged 64.6 nmol/L (or 13 microg/L) with values ranging from
      0.25 to 240 nmol/L. Of the sample, 82.5% had Hg concentrations above the US-EPA
      blood guide-line of 5.8 microg/L. Tuna was the fish species which contributed the
      most to Hg exposure. High selenium and LC-PUFAs may counterbalance the potential
      risk of prenatal exposure to Hg in French Polynesia. Due to the high fish
      consumption of mothers, Polynesian newborns are prenatally exposed to high doses
      of mercury. Although selenium and omega-3 fatty acids may counteract mercury
      toxicity, informing pregnant women on both the mercury and nutrient content of
      local fish species is important.

PMID- 18818169
TI  - A comparison of the prevalence of the metabolic syndrome in the United States
      (US) and Korea in young adults aged 20 to 39 years.
AB  - This study estimated and compared the prevalence of the Metabolic Syndrome and
      its individual components in young adults (ages 20-39 years) in the US and Korea
      using 2003-2004 US and 2005 Korean National Health and Nutrition Examination
      Survey data. The mean body mass index and rate of metabolic abnormalities in the
      US were significantly higher than in Korea. The prevalence of the Metabolic
      Syndrome in the US was nearly three times higher than in Korea using National
      Cholesterol Education Program-Adult Treatment Panel III and Inter-national
      Diabetes Federation criteria (21.6% vs. 6.9% and 23.0% vs. 6.9%, p <0.001). The
      prevalence of abdominal obesity, hyperglycemia, and hypertriglyceridemia was
      higher in the US while the prevalence of low high density lipoprotein-cholesterol
      level was higher in Korea. The rate of hypertension showed no significant
      difference while mean systolic blood pressure and diastolic blood pressure varied
      between the two countries. The proportion of subjects having at least one
      component of Metabolic Syndrome was similar in both countries; however, multiple
      abnormalities were more common in the US. These findings indicate the need for
      the development of race/ethnic-based norms for components of the Metabolic
      Syndrome and detailed analysis of the risk factors for the Metabolic Syndrome in
      the two countries. National health policies designed to prevent the Metabolic
      Syndrome, its individual abnormalities, and its complications using population
      based characteristics of each nation will generate improved outcomes.

PMID- 18818170
TI  - What's on Malaysian television? - A survey on food advertising targeting
      children.
AB  - The Malaysian government recently introduced a ban on fast food advertisements
      targeting children on television. This study reports on data covering 6 months of
      television food advertising targeting children. Six out of seven of the Nation's
      commercial television networks participated (response rate = 85.7%). Based on
      reported timings of children's programmes, prime time significantly differed ( p
      <0.05) between weekdays (mean = 1.89 +/- 0.18 hr) and weekends (mean = 4.61 +/-
      0.33 hr). The increased trend during weekends, school vacation and Ramadhan was
      evident. Over the six-month period, the mean number of food advertisements
      appearing per month varied greatly between television stations (C = 1104; D =
      643; F = 407; B = 327; A = 59; E = 47). Food advertising also increased the most
      in September (n = 3158), followed by July (n = 2770), August (n = 2431), October
      (n = 2291), November (n = 2245) and June (n = 2211). Content analysis of
      advertisements indicated snacks were the highest (34.5%), followed by dairy
      products (20.3%), sugars and candies (13.4%), biscuits (11.2%), fast food (6.7%),
      breakfast cereal (6.4%), beverages (4.1%), supplements (0.9%), rice (0.6%),
      noodles (0.5%), bread (0.3%), miscellaneous and processed foods (0.2%).
      Paradoxically, we found that the frequency of snack food advertised during
      children's prime time was 5 times more than fast foods. The sodium content (mean
      = 620 mg per 100g) of these snack foods was found to be highest.

PMID- 18818171
TI  - Association between obesity and medical care expenditure among Taiwanese adults.
AB  - The aim of this study is to evaluate the relationships between obesity and
      medical care expenditure among Taiwanese adults and to assess the influence of
      sex, age and socioeconomic status. Our study sample consisted of 12,250 adults
      aged 18 years or older from the 2001 National Health Interview Survey (NHIS), who
      had consented to the linking of their survey responses with their NHI claims
      records. Obesity was defined by Body Mass Index based on the WHO-Asia Pacific
      categories. Adjusted expenditure for obese class II and class I men were,
      respectively, 44.6% (95%CI: 27.1%-68.7%) and 39.5% (95%CI: 39.4%-41.2%) greater
      than normal weight men. For obese class II and class I women, the adjusted
      expenditure were, respectively, 93.3% (95%CI: 69.9%-114.6%) and 56.1% (95%CI:
      50.4%-61.4%) greater than normal weight women. After adjusting for other factors,
      higher medical care expenditure was associated with a higher BMI for each age
      group. The relative magnitude of the association became more apparent as age
      increased. Annual medical care expenditure increased as the BMI increased among
      women, which was particularly apparent among low socioeconomic status women. On
      the other hand, the relationship between BMI and medical care expenditure in men
      varied by household income. In conclusion, there is a strong positive
      relationship between higher BMI and increased medical care expenditure and this
      varies according to sex, age and socioeconomic status. Our findings suggest that
      projections of future health care costs attributable to obesity will need to take
      into consideration the demographic make-up of the obese population.

PMID- 18818172
TI  - Coexistence of anaemia and the metabolic syndrome in adults in Jiangsu, China.
AB  - OBJECTIVE: To determine the prevalence of anaemia and the metabolic syndrome with
      special interest in the coexistence of these two problems as well as the possible
      links. RESEARCH DESIGN AND METHOD: In a cross-sectional household survey, 1294
      men and 1522 women aged 20 years and above were interviewed; anthropometric
      measurements and blood samples were taken. Metabolic syndrome was defined
      according to IDF 2005 standard. Anaemia was defined as haemoglobin level below 13
      g/dL for men and 12 g/dL for women. RESULTS: The age-adjusted prevalence of
      metabolic syndrome was 11.2% and of anaemia 24.4%. About 3 percent of the
      participants had both anaemia and metabolic syndrome. Women had a higher
      prevalence of both the metabolic syndrome and anaemia than men (14.0 vs 8.4%,
      31.5% vs 16.1%). Anaemia coexisted significantly with all the individual
      components of the metabolic syndrome. Only 7.0% of the sample had anaemia without
      any individual component of metabolic syndrome. In women, the prevalence of
      combined anaemia and metabolic syndrome peaked in the age group 50-59 years
      (9.9%). Women in the highest quartile of serum ferritin had a higher risk of only
      the metabolic syndrome and coexistence of anaemia and metabolic syndrome.
      CONCLUSION: The high prevalence of the metabolic syndrome and anaemia in the area
      show the urgent need to develop comprehensive strategies aimed at prevention and
      treatment. In women this coexistence may be related to inflammation but further
      research is needed.

PMID- 18818173
TI  - An integrated intervention program to control diabetes in overweight Chinese
      women and men with type 2 diabetes.
AB  - This study evaluated a structured and integrated intervention program on diabetes
      management in individuals with type 2 diabetes in Shanghai, China. Men and women
      with type 2 diabetes and body mass index > 23 kg/m2 were randomized into a 24
      week, prospective, randomized clinical trial. The Reference Group (n=50) received
      diabetes education including diet and physical activity instruction only; the
      Intervention Group (n=100) received more intensive intervention, including
      diabetes education with frequent blood glucose monitoring, nutritional
      counseling, meal plans with diabetes-specific nutritional meal replacement, and
      weekly progress updates with study staff. Major study assessments were obtained
      at baseline, and after 12 and/or 24 weeks of intervention. The Intervention Group
      improved fasting blood glucose, insulin, systolic and diastolic blood pressures
      compared to Reference Group ( p <0.05). Importantly, HbA1c was lower ( p <0.001)
      in the Intervention Group at 12 weeks (-0.6 +/- 0.1%) and 24 weeks (-0.8 +/-
      0.1%). Weight loss was modest, but significant differences were observed between
      groups ( p <0.05). Weight change from baseline after 12 and 24 weeks was -2.8 +/-
      0.2% and -3.7 +/- 0.3%, respectively, in the Intervention Group vs -1.8 +/- 0.4%
      and -2.5 +/- 0.4% in the Reference Group. Additionally, waist and hip
      circumferences and waist:hip ratio decreased in the Intervention compared to the
      Reference Group ( p <0.05). In conclusion, this study demonstrates that Chinese
      men and women with type 2 diabetes following an integrated intervention program
      including diabetes education, frequent blood glucose monitoring and daily use of
      a diabetes-specific meal replacement, can achieve significant improvements in
      glycemic control and markers of cardiovascular health.

PMID- 18818174
TI  - Intraoperative infusion of acetated Ringer solution containing glucose and
      ionized magnesium reduces ketogenesis and maintains serum magnesium.
AB  - The effect of glucose infusion during surgery on glucose metabolism has not been
      investigated sufficiently. We, therefore, examined the effect after the infusion
      of 1% glucose acetated Ringer solution containing Mg2+ during surgery on
      ketogenesis and serum Mg2+ concentrations. Patients, classified as ASA I-II, age
      51-80 years, were randomly assigned to receive infusion of acetated Ringer
      solution. The G/Mg group received infusion with 1% glucose, Na+ 140mEq/L, Mg2+ 2
      mEq/L, and the C group received infusion with glucose free solution containing
      Na+ 130 mEq/L without Mg2+. Both solutions were infused at a rate of 25 mL/kg for
      the first hour, and main-tained at 4 mL/kg/hr thereafter. Blood samples were
      collected three times: before infusion and at 1 hour and 4 hours after the start
      of infusion. Electrolytes and glucose metabolism were evaluated at each sampling.
      After rapid infusion, blood glucose level significantly increased to 170+/
      19mg/dL in the G/Mg group, but it returned to close to baseline after 4 hours and
      serum ketone bodies did not increase during infusion. In the C group, however,
      blood glucose never increased beyond 110 mg/dL, but both acetoacetic and
      hydroxybutyric acids increased significantly at the third measurement.

PMID- 18818175
TI  - Symposium on understanding and influencing consumer food behaviours for health:
      executive summary report.
AB  - Food consumption patterns in Asia are rapidly changing. Urbanization and changing
      lifestyles have diminished the consumption of traditional meals based on cereals,
      vegetables and root crops. These changes are accompa-nied by an increasing
      prevalence of chronic diseases among Asian populations. ILSI Southeast Asia and
      CSIRO, Australia jointly organized the Symposium on Understanding and Influencing
      Food Behaviours for Health, focusing on the use of consumer science to improve
      food behaviour. The goals of the Symposium were to present an understanding of
      Asian consumers and their food choices, examine the use of consumer research to
      modify food choices towards better health, illustrate how health programs and
      food regulations can be utilized effectively to promote healthier choices, and
      identify knowledge gaps regarding the promotion of healthy food behaviour in
      Asian populations. There is no difference in taste perception among Asians, and
      Asian preference for certain tastes is determined by exposure and familiarity
      largely dictated by culture and its underlying values and beliefs. Cross-cultural
      validity of consumer science theories and tools derived from western populations
      need to be tested in Asia. Information on consumption levels and substitution
      behaviours for foods and food products, obtained using consumer research methods,
      can guide the development of food regulations and programs that will enable
      individuals to make healthier choices. Existing knowledge gaps include consumer
      research techniques appropriate for use in Asian settings, diet-health
      relationships from consumption of traditional Asian diets, and methods to address
      the increasing prevalence of over- and undernutrition within the same households
      in Asia.

PMID- 18818176
TI  - The 2nd International Conference on East-West Perspectives on Functional Foods:
      Science, Innovations and Claims.
AB  - The 2nd International Conference on East-West Perspective on Functional Foods
      held in Kuala Lumpur, Malaysia, on November, 2007, discussed the current work on
      some traditional Asian foods and new technologies that offer both challenges and
      opportunities for functional foods. The highlight of the conference was on the
      current regulatory status of nutrition and health claims related to functional
      foods and the experiences in some countries on the substantiation of claims.
      Attention was also given to strategies for effective communication of functional
      foods to consumers. The conference concluded with recommendations to strengthen R
      and D efforts and harmonization of protocols and methodologies on functional
      foods within the region.

PMID- 18818177
TI  - Introduction and history of the Hungarian project for monitoring suicide attempts
      in pregnant women.
AB  - The introduction describes the series of manuscripts resulting from the Hungarian
      Project for monitoring suicide attempts in pregnant women, as well as a history
      of the project, its various phases and participating individuals. This unique
      database contains information on all patients who attempted suicide by "self
      poisoning" and were cared for at central toxicological inpatient clinic in
      Budapest, between 1960 and 1993. A total of 1044 patients were pregnant women, of
      which 19 died and 411 delivered live-born babies. Of these 411 live-born
      children, 367 exposed children were examined and/or evaluated. This is the first
      report of data on the human teratogenic potential of 93 medicinal products
      separately used for a suicide attempt during pregnancy. Each manuscript presents
      results for drugs used by at least 10 pregnant women for a suicide attempt,
      whereas the final paper summarizes the data of drugs used rarely for suicide
      attempt by pregnant women. Each patient consented to participate in the study.
      Critical information collected under medical supervision included examination of
      the patients upon admittance, stage of pregnancy at suicide attempt, blood levels
      of the drug(s) taken for the suicide attempt (at admittance), evaluation of the
      infant at birth for gestational age, weight and congenital abnormalities, and
      follow-up studies for 2 years after a child's birth. These studies provide
      insight into the potential effects of a high dose of a drug or drugs taken during
      pregnancy because it is well accepted that "pulse high doses" of a drug during
      the initial susceptible period of pregnancy are those most likely to result in
      congenital abnormality. Although it is obvious that these data are not sufficient
      to ensure safety, and that it is necessary to have a larger population of exposed
      children, to achieve better statistical power, as well as to include data on
      other populations, this collection of papers provides an important introduction
      of the so-called disaster epidemiological approach in human teratology. It shows
      the feasibility of such studies and suggests that an international surveillance
      system of self-poisoned pregnant women would be useful to better estimate risk
      and benefit of drug use during pregnancy. It is envisioned that the information
      provided will assist physicians and mothers in making better decisions regarding
      drug exposure during pregnancy.

PMID- 18818178
TI  - Self-poisoning during pregnancy as a model for teratogenic risk estimation of
      drugs.
AB  - The results of animal investigations cannot be directly extrapolated to pregnant
      women. Clinical and analytical epidemiological studies for human teratogenic
      risks have many inherent methodological problems and their predictions must be
      regarded with caution. Evaluation of the potential teratogenicity of extremely
      large doses of drugs in self-poisoned pregnant women who attempted suicide offers
      a unique model for finding associations between congenital abnormalities and
      different drugs. All self-poisoned patients were cared for at a toxicological
      inpatient clinic in Budapest, between 1960 and 1993. Out of 1044 pregnant women
      identified from three different periods of the project, 19 died. Women who
      survived were visited at home to reveal birth outcomes, and their children were
      evaluated medically to identify congenital abnormalities and to estimate
      cognitive-behavioral status. The previous or subsequent children of these
      pregnant women were used as controls. In general, self-poisoned pregnant women
      were young (peak age was 18 to 20 years) and primiparous; 55% were unmarried and
      of lower socioeconomic status. Suicide attempts with drugs were most frequent in
      the fourth postconceptional week and second pregnancy month. Of 1044 self
      poisoned pregnant women, 411 delivered live-born babies, of which 367 children
      (89.3%) were evaluated. The self-poisoning model appears to have several benefits
      (e.g., dose-response estimation) in comparison with other methods. It is
      suggested that an international monitoring system of self-poisoned pregnant women
      should be established to provide a larger database.

PMID- 18818179
TI  - No association found between use of very large doses of diazepam by 112 pregnant
      women for a suicide attempt and congenital abnormalities in their offspring.
AB  - The teratogenic potential of diazepam is debated. The objective of this study was
      to examine the effects of extremely high doses of diazepam used for attempted
      suicide during pregnancy on embryo-fetal development. Pregnant women were
      identified from the female patients of the Department of Toxicology Internal
      Medicine, Koranyi Hospital, Budapest, who had been admitted as self-poisoned
      subjects from the three million people of Budapest and the surrounding region.
      This evaluation compares the incidences and types of congenital abnormalities
      observed in exposed children born to mothers who attempted suicide with diazepam
      alone or in combination with other drugs during pregnancy with their sib
      controls. The database consists of a total of 1044 women with self-poisoning
      during pregnancy between 1960 and 1993. Of these 1044 self-poisoned pregnant
      women, 229 (21.9%) used diazepam with or without other drugs for a suicide
      attempt; 112 of these women delivered live-born infants. Doses of diazepam taken
      ranged between 25 and 800 mg. Of 112 exposed children, 15 (13.4%) had congenital
      abnormalities, whereas of their 112 matched sibs, eight (7.1%) had congenital
      abnormalities (odds ratios with 95% confidence intervals: 2.0, 0.8-5.0). Of 37
      pregnant women who attempted suicide between the 4th and 12th postconceptional
      weeks, five (13.5%) delivered live-born babies with a congenital abnormality
      (undescended testis in two exposed children; congenital dysplasia of the hip,
      talipes equinovarus deformation type, congenital inguinal hernia-each in one
      exposed child). The suicide attempts of the mothers of these children did not
      occur during the critical periods for induction of these defects, indicating that
      the observations were unrelated to diazepam. The very large doses of diazepam
      used for self-poisoning during pregnancy did not increase the rate of congenital
      abnormalities in the offspring.

PMID- 18818180
TI  - A study of the teratogenic and fetotoxic effects of large doses of
      chlordiazepoxide used for self-poisoning by 35 pregnant women.
AB  - The human teratogenic potential of chlordiazepoxide is debated. To study the
      effects on the fetal development of very large doses of chlordiazepoxide that
      were used for a suicide attempt during pregnancy, self-poisoned pregnant women
      were identified from patients in a toxicological inpatient clinic in Budapest,
      Hungary. Comparisons were made between congenital abnormalities, intrauterine
      fetal development, and cognitive-behavioral status of the exposed children born
      to mothers who attempted suicide with chlordiazepoxide alone or in combination
      with other drugs during pregnancy and their sib controls. Of 1044 women with self
      poisoning during pregnancy between 1960 and 1993, 88 (8.4%) used chlordiazepoxide
      with or without other drugs for suicide attempt; 35 of these women delivered live
      born infants. Doses of chlordiazepoxide taken ranged between 20 and 300 mg, with
      a mean of 117 +/- 86 mg. Of 35 exposed children, six (17.1 %) were affected with
      congenital abnormalities compared with three (13.6%) of their 22 sibs (OR with
      95% CI: 1.3 (0.3-4.4). Of 18 pregnant women who attempted suicide between the 4th
      and 12th postconceptional week, the period most sensitive to congenital
      malformation, four delivered live-born children affected with a congenital
      abnormality (atrial septal defect type II, complex defect of respiratory system,
      mild pyelectasis because of the stenosis of ureteropelvic junction, congenital
      inguinal hernia). Two other children had fetal alcohol syndrome and unrecognized
      multiple congenital abnormality including talipes equinovarus, deformation type,
      and four minor anomalies. The pregnancy age-specific mean birth weight indicated
      intrauterine fetal growth retardation, which was confirmed by a dose-response
      relationship and by the higher rate of low birth-weight newborns. Cognitive
      status and behavioral scale of exposed children did not indicate neurotoxic
      effects. Very large doses of chlordiazepoxide used for suicide attempts during
      pregnancy did not induce a higher rate of congenital abnormalities but were
      associated with dose-dependent intrauterine growth retardation.

PMID- 18818181
TI  - An evaluation of data for 10 children born to mothers who attempted suicide by
      taking large doses of alprazolam during pregnancy.
AB  - FDA has identified alprazolam, a new type of benzodiazepine, as pregnancy
      category D. The objective of this study was to evaluate the effects on fetal
      development of very large doses of alprazolam that were used for suicide attempts
      during pregnancy. Pregnant women were identified among the patients of the
      Department of Toxicology Internal Medicine, Koranyi Hospital, Budapest, who were
      admitted as self-poisoned subjects from a total population of the three million
      people of Budapest and its surrounding region. Rates of congenital abnormalities,
      intrauterine fetal development, and cognitive-behavioral status were compared
      between children born to mothers who attempted suicide during pregnancy using
      alprazolam alone or in combination with other drugs and in their sib controls.
      Between 1984 and 1993, 559 pregnant women attempted suicide during pregnancy with
      drugs: 30 of these women self-poisoned with alprazolam, 10 delivered live-born
      infants who were examined. Doses of alprazolam used were between 7.5 and 100 mg,
      with a mean of 30 mg. Six of the 10 exposed children were born to mothers who
      attempted suicide between the 6th and 12th postconceptional weeks. Of the 10
      exposed children, two had congenital abnormalities. One had a multiple congenital
      abnormality that included atypical gastroschisis and minor anomalies; an
      association of this defect and the 30 mg alprazolam used for self-poisoning in
      the 14th postconceptional week cannot be excluded. Another exposed child had mild
      pectus excavatum, but the times of the suicide attempt and the critical period
      for producing this defect did not overlap. Of 12 sibs, one had a multiple
      congenital abnormality. Thus, the rate of congenital abnormalities did not
      significantly differ between exposed children and their sibs. Mean birth weight
      was higher for babies born to mothers who attempted suicide by alprazolam during
      pregnancy than in their sib controls. Cognitive status and behavioral scale of
      the exposed children did not indicate fetotoxic effects, including neurotoxic
      effects, of large doses of alprazolam. The large doses of alprazolam used for
      self-poisoning during pregnancy did not result in a significantly higher rate of
      congenital abnormalities; however, there were only 10 self-poisoned pregnant
      women, and an association of one multiple congenital abnormality with a large
      dose of alprazolam cannot be excluded. The findings in this study did not
      identify fetotoxicity, including neurotoxicity, of very large doses of
      alprazolam. Our study shows that the self-poisoning model is feasible and
      provides beneficial information for use in estimating human teratogenic and
      fetotoxic risks of drugs.

PMID- 18818182
TI  - A study of the effects of large doses of medazepam used for self-poisoning in 10
      pregnant women on fetal development.
AB  - The purpose of this article is to report an evaluation of the teratogenic and
      fetotoxic potential of medezepam in humans based on pregnant women who used very
      large doses of medazepam for a suicide attempt. All self-poisoned patients were
      cared for at the Department of Toxicology Internal Medicine, Koranyi Hospital, a
      toxicological inpatients clinic in Budapest, Hungary, between 1960 and 1993.
      Pregnant women were identified from self-poisoned subjects admitted from a
      population base of three million people of Budapest and the surrounding region.
      The rates of congenital abnormalities (CAs), intrauterine fetal development,
      cognitive and behavioral status in children born to mothers who attempted suicide
      with medazepam alone or in combination with other drugs during pregnancy was
      compared in their sib controls. Between 1980 and 1993, 835 pregnant women in our
      study attempted suicide during pregnancy with drugs. Of these, 314 delivered live
      born infants and 283 were examined and/or evaluated. Thirty-two (3.8%) of these
      835 pregnant women used medazepam with or without other drugs for self-poisoning;
      10 of these women delivered live-born babies. The dose of medazepam used for the
      suicide attempt ranged between 60 and 500 mg, with a mean of 276 mg. Eight of the
      32 suicide attempts involving medazepam occurred between the 4th and 12th
      postconceptional weeks. Of the 10 live-born exposed children, one was affected
      with congenital inguinal hernia; one of the 13 sib controls had a lethal
      hydronephrosis. No adverse effects were observed on intrauterine growth,
      cognitive status, or behavioral deviations in the 10 children born to mothers who
      attempted suicide with medazepam during pregnancy. Very large doses of medazepam
      were used for self-poisoning during pregnancy. These doses did not increase the
      rate of CAs even though eight mothers attempted suicide during the most critical
      period for production of CAs. No fetotoxic, including neurotoxic, effects of
      exposure of live-born children to a very large dose of medazepam were observed.
      Our experiences show the feasibility and benefits of use of the self-poisoning
      model in estimating human teratogenic and fetotoxic risks of drugs.

PMID- 18818183
TI  - A study of the effects of large doses of glutethimide that were used for self
      poisoning during pregnancy on human fetuses.
AB  - Animal investigations showed some embryolethal and teratogenic effects of
      glutethimide, a piperidindion derivative non-barbital hypnotic drug. Thus, the
      objective of this study was to evaluate the effects of very large doses of
      glutethimide that were used for a suicide attempt during pregnancy on the embryo
      fetal development of exposed children. Self-poisoned pregnant women were
      identified from the population of female patients of the Department of Toxicology
      Internal Medicine, Koranyi Hospital, Budapest who had been admitted from the 3
      million people of Budapest and its surrounding region. The rates of congenital
      abnormalities, intrauterine fetal development (based on birth weight and
      pregnancy age at delivery) and cognitive-behavioral status of exposed children
      born to mothers who attempted suicide with glutethimide alone or in combination
      with other drugs during pregnancy were compared with their sib controls. Of 1044
      pregnant women with self-poisoning during pregnancy between 1960 and 1993, 33
      used glutethimide for a suicide attempt sixteen of these women delivered live
      born infants. The dose of glutethimide ranged between 1000 and 15,000 mg with a
      mean of 4234 mg. Of the 16 exposed children, five were male and 11 were female.
      Three exposed children were affected with congenital abnormalities (atrial septal
      defect type II, pectus carinatum, fetal alcohol syndrome). Of their 16 matched
      unexposed sib pairs, two had congenital abnormalities. The mean birth weight of
      the exposed children was somewhat larger due to somewhat longer pregnancy age at
      delivery. Cognitive status and behavioral scale of the exposed children did not
      indicate a fetotoxic (including neurotoxic) effect of large doses of
      glutethimide. Very large doses of glutethimide used for a suicide attempt by 16
      pregnant women did not produce teratogenic or fetotoxic (including neurotoxic)
      effects in their children.

PMID- 18818184
TI  - A study of the teratogenic and fetotoxic effects of large doses of amobarbital
      used for a suicide attempt by 14 pregnant women.
AB  - The teratogenic effect of barbitals is debated, and this study was performed to
      identify the effects of very large doses of amobarbital used for suicide attempts
      during pregnancy on embryo-fetal development. Self-poisoned pregnant women were
      identified from patients of the Department of Toxicology Internal Medicine,
      Koranyi Hospital, Budapest, Hungary, who were admitted from the 3 million people
      of Budapest and its surrounding region. A comparison was made between outcomes of
      pregnancies of women who attempted suicide with amobarbital alone or in
      combination with other drugs during pregnancy with sib controls. Of 1044 women
      with self-poisoning during pregnancy between 1960 and 1993, 33 used amobarbital
      for a suicide attempt. Of these 33 women, 14 delivered live-born babies. The dose
      of amobarbital taken by these women ranged between 600 and 10,000 mg, with a mean
      of 3886 mg. Of the 14 amobarbital-exposed children, 9 had mothers who attempted
      suicide between the 3rd and 12th post-conceptional weeks. None of these children
      had a congenital abnormality, and there was no evidence of fetal growth
      retardation. The distribution of cognitive status and behavioral scale of the
      exposed children were comparable with those of their sibs although one exposed
      child had a very low (about 75) IQ, whereas another one was treated because of a
      very severe aggressive behavioral deviation. Exposure to very large doses of
      amobarbital that were used for self-poisoning during pregnancy did not produce
      teratogenic effects in this study.

PMID- 18818185
TI  - A study of the potential teratogenic effect of large doses of promethazine used
      for a suicide attempt by 32 pregnant women.
AB  - In Hungary, promethazine, a phenothiazine antihistamine, is the second most
      frequently used drug during pregnancy. The purpose of this study was to examine
      the effects of very large doses of promethazine that were used for a suicide
      attempt during pregnancy on embryo-fetal development. Self-poisoned pregnant
      women were identified from patients of the Department of Toxicology Internal
      Medicine, Koranyi Hospital, Budapest, who were admitted from the three million
      people of Budapest and surrounding region. The rate of congenital abnormalities,
      intrauterine development (based on pregnancy age at delivery and birth weight),
      and cognitive-behavioral status of exposed children born to mothers who attempted
      suicide with promethazine alone or in combination with other drugs during
      pregnancy was compared with their sib controls. In all, 89 of the 1044 women with
      self-poisoning during pregnancy between 1960 and 1993 used promethazine for a
      suicide attempt. Of these 89 women, 32 delivered newborn babies. The dose of
      promethazine taken by these women for self-poisoning ranged between 125 mg and
      1750 mg (mean of 544 mg, i.e., 21.8 tablets). Of the 32 promethazine-exposed
      children, nine (28.1 %) were affected with congenital abnormalities. However, of
      11 pregnant women who attempted suicide with promethazine between the 3rd and
      12th postconceptional week, that is, the critical period for production of most
      major congenital abnormalities, only three were affected with defects, and the
      critical periods for producing these defects did not overlap with the time of the
      suicide attempt during pregnancy. Of 34 unexposed sibs, five (14.7%) had
      congenital abnormalities; the difference in the total rate of congenital
      abnormalities between the exposed children and their sib controls was not
      significant. There also was no difference in pregnancy age-specific birth weight
      between exposed children and their sibs. Mean intelligence quotient was not
      reduced, and the incidence of behavioral deviation was not increased in the
      exposed children. The findings of this study did not indicate teratogenic or
      fetotoxic (including neurotoxic) effects of large doses of promethazine in
      children born to mothers who self-poisoned during pregnancy, although the total
      rate of congenital abnormalities was very high. Our experience shows the
      feasibility and benefits of using the self-poisoning model in estimating human
      teratogenic/fetotoxic risks of exposure to drugs.

PMID- 18818186
TI  - A study of teratogenic and fetotoxic effects of large doses of meprobamate used
      for a suicide attempt by 42 pregnant women.
AB  - The human teratogenic effect of meprobamate is debated. Thus, the available data
      set regarding very large doses of meprobamate used for a suicide attempt during
      pregnancy was evaluated for effects on fetal development. Pregnant women were
      identified from self-poisoned subjects of a total population of approximately
      three million people (Budapest and surrounding region) who were admitted to the
      Department of Toxicology Internal Medicine, Koranyi Hospital, Budapest.
      Comparisons were made of congenital abnormalities, intrauterine fetal growth, and
      cognitive-behavioral status in exposed children born to mothers who attempted
      suicide with meprobamate alone or in combination with other drugs during
      pregnancy with their control sibs. Of 1044 women with self-poisoning during
      pregnancy between 1960 and 1993, 107 (10.3%) used meprobamate, with or without
      other drugs for a suicide attempt; 42 of these 107 women delivered live-born
      infants. The dose of meprobamate used for the suicide attempt ranged between 1000
      and 26,000 mg, with a mean of 3690 mg. Of 42 exposed children, seven (16.7%) were
      affected with congenital abnormalities, however, of their 27 sib controls, four
      had a CA (14.8%) (OR with 95% CI: 1.7, 0.5-4.9) of 14 had a congenital
      abnormality. Of 14 mothers who attempted suicide during the 4-12th
      postconceptional week, two delivered live-born babies affected with mild isolated
      congenital abnormality: undescended testis and congenital dysplasia of the hip.
      However, the critical period for production of these two defects did not overlap
      with the time of the mother's suicide attempt. Mean birth weight and pregnancy
      age, cognitive status, and behavioral scale of the exposed children did not
      indicate fetotoxic, including neurotoxic, effects of large doses of meprobamate.
      Very large doses of meprobamate that were used for self-poisoning during
      pregnancy did not result in teratogenic or fetotoxic, including neurotoxic,
      effects on fetal development.

PMID- 18818187
TI  - A study of the teratogenic and fetotoxic effects of large doses of barbital,
      hexobarbital and butobarbital used for suicide attempts by pregnant women.
AB  - The teratogenic potential of barbiturates is debated. The objective of this study
      was to evaluate the effects of very large doses of different barbiturates, except
      phenobarbital and amobarbital, on fetal development in pregnant women who
      attempted suicide. These self-poisoned pregnant women were identified among the
      patients of the Department of Toxicology Internal Medicine, Koranyi Hospital,
      Budapest. The prevalence at birth of congenital abnormalities and intrauterine
      fetal growth, based on pregnancy age at delivery and birth weight, as well as
      cognitive-behavioral status in exposed children born to mothers who attempted
      suicide with barbiturates alone or in combination with other drugs, during
      pregnancy, were compared with their sibs as controls. Of 1044 women with self
      poisoning during pregnancy between 1960 and 1993, 411 delivered live-born babies;
      of these, 367 (89.3%) exposed children were evaluated. Of the 367 exposed
      children, 6, 5, 4 and 4 were born to mothers who attempted suicide with very
      large doses of Barbamid (butobarbital and aminophenazone), hexobarbital,
      butobarbital and Belloid (butobarbital, hyoscyamine and secalis cornuti
      alkaloida) tablets, respectively. Of 19 exposed children, two children with a
      congenital inguinal hernia were born to mothers who attempted suicide with 30
      tablets of Belloid (900 mg butobarbital) in the 20th postconceptional week or
      with 20 tablets of Belloid in combination with chlordiazepoxide (100 mg) and
      nitrazepam (100 mg) in 12th postconceptional week. However, the critical period
      for production of congenital inguinal hernia is in the last months of pregnancy.
      None of the exposed children born to the other 12 pregnant women who attempted
      suicide with these barbiturates between the third and 12th postconceptional week,
      i.e., during the critical period for production of most major congenital
      abnormalities, had a congenital abnormality. Congenital abnormalities did not
      occur among 16 sib controls. Intrauterine fetal growth was similar between sibs
      and exposed children; cognitive status and behavioral scale also did not indicate
      any neurotoxic effects from large doses of these barbiturates. The very large
      doses of barbital, hexobarbital and/or butobarbital used for self-poisoning
      during pregnancy were not teratogenic to the children, although it must be
      recognized that the number of exposed children was limited.

PMID- 18818188
TI  - A study of the potential teratogenic effects of large doses of drugs rarely used
      for a suicide attempt during pregnancy.
AB  - The available data set regarding pregnant women who attempted suicide during
      pregnancy was evaluated to estimate the teratogenic effect of very large doses of
      drugs based on the rate and distribution of congenital abnormalities of exposed
      children. These pregnant women were identified from patients of central
      toxicological inpatients clinic, Budapest, Hungary, 1960-1993. Of 1044 women with
      self-poisoning during pregnancy, 411 delivered live-born babies; 367 of these
      children were examined in this study. Data for 12 frequently used (10 or more
      times) drugs were published previously; this paper presents 77 medicines (58
      drugs and 19 medicinal products including multiple components) that were rarely
      used for a suicide attempt by 197 pregnant women. Although 23 (11.7%) exposed
      children had congenital abnormalities (CAs), in general, a causal relationship of
      the CA and the drug taken by the pregnant woman cannot be assumed. This is
      because the suicide attempt often did not occur during a critical period for
      producing the CA. Of 67 pregnant women who attempted suicide between the 3rd and
      12th postconceptional week, that is, the critical period of most major CAs, 7
      (10.5%) children were affected with CAs. This high rate of CAs in exposed
      children can be explained by the intensive medical examinations, including
      diagnosis of mild CAs and minor anomalies, or the low socioeconomic status and
      hazardous lifestyle of mothers. None of the rarely used drugs was identified as a
      potential human teratogen. Experience of the authors shows the feasibility and
      benefits of using the self-poisoning model in estimating human
      teratogenic/fetotoxic risks of exposure to drugs.

PMID- 18818189
TI  - Combined neuroimaging, neurocognitive and psychiatric factors to predict alcohol
      consumption following treatment for alcohol dependence.
AB  - AIMS: Resumption of hazardous drinking after treatment is common in alcohol use
      disorders (AUD). This study examined the ability of multimodality magnetic
      resonance, neurocognitive, psychiatric and demographic, to predict alcohol
      consumption after treatment for AUD. METHODS: Seventy treatment-seeking
      participants completed 1.5T magnetic resonance studies, yielding regional gray
      matter (GM) and white matter (WM) surrogate markers of neuronal integrity (N
      acetylaspartate: NAA) and cell membrane turnover/synthesis (choline: Cho),
      assessment of major psychiatric disorders and comprehensive neurocognitive
      assessment after approximately 1 month of abstinence. Participants were followed
      up 6-12 months after treatment and classified as Abstainers (no alcohol
      consumption; n=26) and Resumers (any alcohol consumption; n=44). Abstainers and
      Resumers were contrasted on various outcome measures, and those that
      significantly differed between groups were entered as factors in a logistical
      regression model to predict drinking status at follow-up. RESULTS: The following
      variables were independent predictors of resumption of drinking: temporal GM NAA,
      frontal WM NAA, frontal GM Cho, processing speed and comorbid unipolar mood
      disorder. With each standard deviation unit decrease in temporal GM NAA, frontal
      WM NAA, frontal GM Cho and processing speed, the odds of resumption of drinking
      were increased 3.1, 3.3, 6.4 and 14.2 times, respectively. Diagnosis of a
      unipolar mood disorder was associated with 14.5-fold increased odds of resumed
      drinking. CONCLUSIONS: The findings suggest that Resumers, relative to
      Abstainers, demonstrated greater abnormalities in anterior frontal-subcortical
      circuits involved in mood and behavioral regulation, and development and
      maintenance of alcohol use disorders, The magnetic resonance-derived variables
      used in this study may provide additional information regarding the prediction
      and neurobiological correlates of resumption of hazardous drinking.

PMID- 18818190
TI  - Validation of a scale for rating the delivery of psycho-social treatments for
      alcohol dependence and misuse: the UKATT Process Rating Scale (PRS).
AB  - AIM: The aim of this study was to describe the development and validation of the
      UK Alcohol Treatment Trial Process Rating Scale (UKATT PRS), a manual based
      method for monitoring and rating the delivery of psychosocial treatments of
      alcohol dependence and misuse. METHODS: Following adaptation and further
      development of a validated rating scale, the ability of the UKATT PRS to rate the
      delivery of video-recorded treatment in the UK Alcohol Treatment Trial (UKATT)
      was tested. RESULTS: Tests of the validity and reliability of the UKATT PRS show
      that it is valid and reliably able to detect the two treatments for which it was
      designed and to discriminate between them. CONCLUSIONS: The UKATT PRS is a valid
      and reliable method of rating the frequency and quality of therapeutic style and
      content in the delivery of two psycho-social treatments of alcohol use and
      dependence.

PMID- 18818191
TI  - Effect of propofol and sevoflurane on coughing in smokers and non-smokers
      awakening from general anaesthesia at the end of a cervical spine surgery.
AB  - BACKGROUND: Coughing during emergence from general anaesthesia may be
      detrimental, particularly after cervical spine surgery. We compared the effect of
      propofol or sevoflurane anaesthesia on the incidence and severity of coughing
      during recovery in patients undergoing cervical spine surgery via an anterior
      approach. As a secondary aim, we also evaluated the influences of smoking and
      estimated residual anaesthetic agent concentrations on coughing. METHODS: Thirty
      four patients were enrolled in a randomized prospective, double-blind study to
      receive either propofol (PPF) or sevoflurane (SEVO) for maintenance of
      anaesthesia. The decision to perform tracheal extubation was based on specified
      criteria, including resumption of spontaneous respiration and consciousness.
      During emergence from anaesthesia and extubation, coughing was observed and
      graded at predefined times. RESULTS: The incidence of severe coughing was higher
      in the SEVO group than in the PPF group (59% and 6%, respectively), and also in
      smokers than in non-smokers (50% and 17%, respectively). The peak incidence of
      coughing was at tracheal extubation. The probability of coughing was influenced
      by the estimated residual concentration of anaesthetic agents at extubation,
      except for smokers in the SEVO group who were at the highest risk of coughing.
      CONCLUSIONS: The incidence of coughing after cervical spine surgery when tracheal
      extubation is performed according to clinical criteria is lower after propofol
      anaesthesia compared with sevoflurane anaesthesia. Smokers are at increased risk
      of coughing, independently of the type of anaesthesia maintenance. Higher
      residual concentrations of anaesthetic agents decrease the probability of
      coughing, except for smokers anaesthetized with sevoflurane.

PMID- 18818192
TI  - Fibrinogen concentrate substitution therapy in patients with massive haemorrhage
      and low plasma fibrinogen concentrations.
AB  - BACKGROUND: Patients experiencing massive haemorrhage are at high risk of
      developing coagulopathy through loss, consumption, and dilution of coagulation
      factors and platelets. It has been reported that plasma fibrinogen concentrations
      may reach a critical low level relatively early during bleeding, calling for
      replacement fibrinogen therapy. Cryoprecipitate has been widely used in the past,
      but more recently, a pasteurized fibrinogen concentrate has become available. We
      audited the effects of fibrinogen concentrate therapy on laboratory and clinical
      outcome in patients with massive haemorrhage. METHODS: We identified 43 patients
      over the previous 2 yr to whom a fibrinogen concentrate had been administered as
      treatment for hypofibrinogenaemia during serious haemorrhage. Platelet count, P
      fibrinogen, activated partial thromboplastin time (APTT), prothrombin time (PT),
      D-dimer, and volume of blood lost were obtained from medical and laboratory
      records. Numbers of units of red blood cells (RBC), fresh frozen plasma (FFP),
      and pooled platelet concentrates were recorded before and after fibrinogen
      substitution. RESULTS: A significant increase in plasma fibrinogen concentration
      was observed after fibrinogen concentrate therapy. Platelet counts and fibrin D
      dimer values remained unchanged, whereas the APTT and PT improved significantly.
      Requirements for RBC, FFP, and platelets were significantly reduced. Blood loss
      decreased significantly. CONCLUSIONS: Off-label substitution therapy with a
      fibrinogen concentrate generally improved global laboratory coagulation results
      and as supplementary intervention, appeared to diminish the requirements for RBC,
      FFP, and platelet substitution in this patient cohort.

PMID- 18818193
TI  - Hearing loss in a mouse model of Muenke syndrome.
AB  - The heterozygous Pro250Arg substitution mutation in fibroblast growth factor
      receptor 3 (FGFR3), which increases ligand-dependent signalling, is the most
      common genetic cause of craniosynostosis in humans and defines Muenke syndrome.
      Since FGF signalling plays dosage-sensitive roles in the differentiation of the
      auditory sensory epithelium, we evaluated hearing in a large group of Muenke
      syndrome subjects, as well as in the corresponding mouse model (Fgfr3(P244R)).
      The Muenke syndrome cohort showed significant, but incompletely penetrant,
      predominantly low-frequency sensorineural hearing loss, and the Fgfr3(P244R) mice
      showed dominant, fully penetrant hearing loss that was more severe than that in
      Muenke syndrome individuals, but had the same pattern of relative high-frequency
      sparing. The mouse hearing loss correlated with an alteration in the fate of
      supporting cells (Deiters'-to-pillar cells) along the entire length of the
      cochlear duct, with the most extreme abnormalities found at the apical or low
      frequency end. In addition, there was excess outer hair cell development in the
      apical region. We conclude that low-frequency sensorineural hearing loss is a
      characteristic feature of Muenke syndrome and that the genetically equivalent
      mouse provides an excellent model that could be useful in testing hearing loss
      therapies aimed at manipulating the levels of FGF signalling in the inner ear.

PMID- 18818194
TI  - Early-onset liver mtDNA depletion and late-onset proteinuric nephropathy in Mpv17
      knockout mice.
AB  - In humans, MPV17 mutations are responsible for severe mitochondrial depletion
      syndrome, mainly affecting the liver and the nervous system. To gain insight into
      physiopathology of MPV17-related disease, we investigated an available Mpv17
      knockout animal model. We found severe mtDNA depletion in liver and, albeit to a
      lesser extent, in skeletal muscle, whereas hardly any depletion was detected in
      brain and kidney, up to 1 year after birth. Mouse embryonic fibroblasts did show
      mtDNA depletion, but only after several culturing passages, or in a serumless
      culturing medium. In spite of severe mtDNA depletion, only moderate decrease in
      respiratory chain enzymatic activities, and mild cytoarchitectural alterations,
      were observed in the Mpv17(-/-) livers, but neither cirrhosis nor failure ever
      occurred in this organ at any age. The mtDNA transcription rate was markedly
      increased in liver, which could contribute to compensate the severe mtDNA
      depletion. This phenomenon was associated with specific downregulation of Mterf1,
      a negative modulator of mtDNA transcription. The most relevant clinical features
      involved skin, inner ear and kidney. The coat of the Mpv17(-/-) mice turned gray
      early in adulthood, and 18-month or older mice developed focal segmental
      glomerulosclerosis (FSGS) with massive proteinuria. Concomitant degeneration of
      cochlear sensory epithelia was reported as well. These symptoms were associated
      with significantly shorter lifespan. Coincidental with the onset of FSGS, there
      was hardly any mtDNA left in the glomerular tufts. These results demonstrate that
      Mpv17 controls mtDNA copy number by a highly tissue- and possibly cytotype
      specific mechanism.

PMID- 18818195
TI  - Structures of human cytochrome P-450 2E1. Insights into the binding of inhibitors
      and both small molecular weight and fatty acid substrates.
AB  - Human microsomal cytochrome P-450 2E1 (CYP2E1) monooxygenates > 70 low molecular
      weight xenobiotic compounds, as well as much larger endogenous fatty acid
      signaling molecules such as arachidonic acid. In the process, CYP2E1 can generate
      toxic or carcinogenic compounds, as occurs with acetaminophen overdose,
      nitrosamines in cigarette smoke, and reactive oxygen species from uncoupled
      catalysis. Thus, the diverse roles that CYP2E1 has in normal physiology,
      toxicity, and drug metabolism are related to its ability to metabolize diverse
      classes of ligands, but the structural basis for this was previously unknown.
      Structures of human CYP2E1 have been solved to 2.2 angstroms for an indazole
      complex and 2.6 angstroms for a 4-methylpyrazole complex. Both inhibitors bind to
      the heme iron and hydrogen bond to Thr303 within the active site. Complementing
      its small molecular weight substrates, the hydrophobic CYP2E1 active site is the
      smallest yet observed for a human cytochrome P-450. The CYP2E1 active site also
      has two adjacent voids: one enclosed above the I helix and the other forming a
      channel to the protein surface. Minor repositioning of the Phe478 aromatic ring
      that separates the active site and access channel would allow the carboxylate of
      fatty acid substrates to interact with conserved 216QXXNN220 residues in the
      access channel while positioning the hydrocarbon terminus in the active site,
      consistent with experimentally observed omega-1 hydroxylation of saturated fatty
      acids. Thus, these structures provide insights into the ability of CYP2E1 to
      effectively bind and metabolize both small molecule substrates and fatty acids.

PMID- 18818196
TI  - Evolutionary differences in glycosaminoglycan fine structure detected by
      quantitative glycan reductive isotope labeling.
AB  - To facilitate qualitative and quantitative analysis of glycosaminoglycans, we
      tagged the reducing end of lyase-generated disaccharides with aniline-containing
      stable isotopes (12C6 and 13C6). Because different isotope tags have no effect on
      chromatographic retention times but can be discriminated by a mass detector,
      differentially isotope-tagged samples can be compared simultaneously by liquid
      chromatography/mass spectrometry and quantified by admixture with known amounts
      of standards. The technique is adaptable to all types of glycosaminoglycans, and
      its sensitivity is only limited by the type of mass spectrometer available. We
      validated the method using commercial heparin and keratan sulfate as well as
      heparan sulfate isolated from mutant and wild-type Chinese hamster ovary cells,
      and select tissues from mutant and wild-type mice. This new method provides more
      robust, reliable, and sensitive means of quantitative evaluation of
      glycosaminoglycan disaccharide compositions than existing techniques allowing us
      to compare the chondroitin and heparan sulfate compositions of Hydra vulgaris,
      Drosophila melanogaster, Caenorhabditis elegans, and mammalian cells. Our results
      demonstrate significant differences in glycosaminoglycan structure among these
      organisms that might represent evolutionarily distinct functional motifs.

PMID- 18818197
TI  - Characterization of active site structure in CYP121. A cytochrome P450 essential
      for viability of Mycobacterium tuberculosis H37Rv.
AB  - Mycobacterium tuberculosis (Mtb) cytochrome P450 gene CYP121 is shown to be
      essential for viability of the bacterium in vitro by gene knock-out with
      complementation. Production of CYP121 protein in Mtb cells is demonstrated.
      Minimum inhibitory concentration values for azole drugs against Mtb H37Rv were
      determined, the rank order of which correlated well with Kd values for their
      binding to CYP121. Solution-state spectroscopic, kinetic, and thermodynamic
      studies and crystal structure determination for a series of CYP121 active site
      mutants provide further insights into structure and biophysical features of the
      enzyme. Pro346 was shown to control heme cofactor conformation, whereas Arg386 is
      a critical determinant of heme potential, with an unprecedented 280-mV increase
      in heme iron redox potential in a R386L mutant. A homologous Mtb redox partner
      system was reconstituted and transported electrons faster to CYP121 R386L than to
      wild type CYP121. Heme potential was not perturbed in a F338H mutant, suggesting
      that a proposed P450 superfamily-wide role for the phylogenetically conserved
      phenylalanine in heme thermodynamic regulation is unlikely. Collectively, data
      point to an important cellular role for CYP121 and highlight its potential as a
      novel Mtb drug target.

PMID- 18818198
TI  - The antiherpetic drug acyclovir inhibits HIV replication and selects the V75I
      reverse transcriptase multidrug resistance mutation.
AB  - The antiviral drug acyclovir is a guanosine nucleoside analog that potently
      inhibits herpes simplex virus (HSV) replication. Acyclovir treatment in patients
      coinfected with HSV and human immunodeficiency virus (HIV) has been observed to
      alter disease course and decrease HIV viral load, a finding that has been
      attributed to indirect effects of HSV suppression on HIV replication. Based on
      this hypothesis, several clinical studies have recently investigated the use of
      acyclovir for treatment of patients coinfected with HSV and HIV or for
      prophylaxis against HIV transmission. In this report, we use a single round HIV
      infectivity assay to show that acyclovir directly inhibits HIV infection with an
      IC50 of approximately 5 microm. The target of acyclovir in HIV-infected cells is
      validated as HIV reverse transcriptase (RT) by the emergence of the RT variant
      V75I under the selective pressure of acyclovir. The V75I mutation is part of the
      multidrug resistance pathway that enhances viral resistance to many of the best
      RT inhibitors approved for the treatment of HIV. Biochemical analyses demonstrate
      that acyclovir triphosphate is a chain terminator substrate for HIV RT and can
      compete with dGTP for incorporation into DNA. Although acyclovir may prove a
      useful lead for development of new HIV treatments, the selection of resistant
      mutants raises a cautionary note to the use of acyclovir monotherapy in patients
      coinfected with HSV and HIV.

PMID- 18818199
TI  - Binding of the unorthodox transcription activator, Crl, to the components of the
      transcription machinery.
AB  - The small regulatory protein Crl binds to sigmaS, the RNA polymerase stationary
      phase sigma factor. Crl facilitates the formation of the sigmaS-associated
      holoenzyme (EsigmaS) and thereby activates sigmaS-dependent genes. Using a real
      time surface plasmon resonance biosensor, we characterized in greater detail the
      specificity and mode of action of Crl. Crl specifically forms a 1:1 complex with
      sigmaS, which results in an increase of the association rate of sigmaS to core
      RNA polymerase without any effect on the dissociation rate of EsigmaS. Crl is
      also able to associate with preformed EsigmaS with a higher affinity than with
      sigmaS alone. Furthermore, even at saturating sigmaS concentrations, Crl
      significantly increases EsigmaS association with the katN promoter and the
      productive isomerization of the EsigmaS-katN complex, supporting a direct role of
      Crl in transcription initiation. Finally, we show that Crl does not bind to
      sigma70 itself but is able at high concentrations to form a weak and transient
      1:1 complex with both core RNA polymerase and the sigma70-associated holoenzyme,
      leaving open the possibility that Crl might also exert a side regulatory role in
      the transcriptional activity of additional non-sigmaS holoenzymes.

PMID- 18818200
TI  - Fibrinogen beta-chain tyrosine nitration is a prothrombotic risk factor.
AB  - Elevated levels of circulating fibrinogen are associated with an increased risk
      of atherothrombotic diseases although a causative correlation between high levels
      of fibrinogen and cardiovascular complications has not been established. We
      hypothesized that a potential mechanism for an increased prothrombotic state is
      the post-translational modification of fibrinogen by tyrosine nitration. Mass
      spectrometry identified tyrosine residues 292 and 422 at the carboxyl terminus of
      the beta-chain as the principal sites of fibrinogen nitration in vivo.
      Immunoelectron microscopy confirmed the incorporation of nitrated fibrinogen
      molecules in fibrin fibers. The nitration of fibrinogen in vivo resulted in four
      distinct functional consequences: increased initial velocity of fibrin clot
      formation, altered fibrin clot architecture, increased fibrin clot stiffness, and
      reduced rate of clot lysis. The rate of fibrin clot formation and clot
      architecture was restored upon depletion of the tyrosine-nitrated fibrinogen
      molecules. An enhanced response to the knob "B" mimetic peptides Gly-His-Arg
      Pro(am) and Ala-His-Arg-Pro(am) suggests that incorporation of nitrated
      fibrinogen molecules accelerates fibrin lateral aggregation. The data provide a
      novel biochemical risk factor that could explain epidemiological associations of
      oxidative stress and inflammation with thrombotic complications.

PMID- 18818201
TI  - Organic anion transporter OAT1 undergoes constitutive and protein kinase C
      regulated trafficking through a dynamin- and clathrin-dependent pathway.
AB  - Organic anion transporter 1 (OAT1) mediates the body disposition of a diverse
      array of environmental toxins and clinically important drugs. Therefore,
      understanding the regulation of this transporter has profound clinical
      significance. We previously demonstrate that OAT1 activity was down-regulated by
      activation of protein kinase C (PKC), kinetically revealed as a decrease in the
      maximum transport velocity V(max) without significant change in the substrate
      affinity K(m) of the transporter. In the current study, we showed that OAT1
      constitutively internalized from and recycled back to the plasma membrane, and
      PKC activation accelerated OAT1 internalization without affecting OAT1 recycling.
      We further showed that treatment of OAT1-expressing cells with concanavalin A,
      depletion of K(+) from the cells, or transfection of dominant negative mutants of
      dynamin-2 or Eps15 into the cells, all of which block the clathrin-dependent
      endocytotic pathway, significantly blocked constitutive and PKC-regulated OAT1
      internalization. We finally showed that OAT1 colocalized with transferrin, a
      marker for clathrin-dependent endocytosis, at the cell surface and in the EEA1
      positive early endosomes. Together, our findings demonstrated for the first time
      that (i) OAT1 constitutively traffics between plasma membrane and recycling
      endosomes, (ii) PKC activation down-regulates OAT1 activity by altering already
      existent OAT1 trafficking, and (iii) OAT1 internalization occurs partly through a
      dynamin- and clathrin-dependent pathway.

PMID- 18818202
TI  - Molecular mechanism of the Syk activation switch.
AB  - Many immune signaling pathways require activation of the Syk tyrosine kinase to
      link ligation of surface receptors to changes in gene expression. Despite the
      central role of Syk in these pathways, the Syk activation process remains poorly
      understood. In this work we quantitatively characterized the molecular mechanism
      of Syk activation in vitro using a real time fluorescence kinase assay,
      mutagenesis, and other biochemical techniques. We found that dephosphorylated
      full-length Syk demonstrates a low initial rate of substrate phosphorylation that
      increases during the kinase reaction due to autophosphorylation. The initial rate
      of Syk activity was strongly increased by either pre-autophosphorylation or
      binding of phosphorylated immune tyrosine activation motif peptides, and each of
      these factors independently fully activated Syk. Deletion mutagenesis was used to
      identify regions of Syk important for regulation, and residues 340-356 of the SH2
      kinase linker region were identified to be important for suppression of activity
      before activation. Comparison of the activation processes of Syk and Zap-70
      revealed that Syk is more readily activated by autophosphorylation than Zap-70,
      although both kinases are rapidly activated by Src family kinases. We also
      studied Syk activity in B cell lysates and found endogenous Syk is also activated
      by phosphorylation and immune tyrosine activation motif binding. Together these
      experiments show that Syk functions as an "OR-gate" type of molecular switch.
      This mechanism of switch-like activation helps explain how Syk is both rapidly
      activated after receptor binding but also sustains activity over time to
      facilitate longer term changes in gene expression.

PMID- 18818203
TI  - G0 function of BCL2 and BCL-xL requires BAX, BAK, and p27 phosphorylation by
      Mirk, revealing a novel role of BAX and BAK in quiescence regulation.
AB  - BCL2 and BCL-x(L) facilitate G(0) quiescence by decreasing RNA content and cell
      size and up-regulating p27 protein, but the precise mechanism is not understood.
      We investigated the relationship between cell cycle regulation and the anti
      apoptosis function of BCL2 and BCL-x(L). Neither caspase inhibition nor
      abrogation of mitochondria-dependent apoptosis by BAX and BAK deletion fully
      recapitulated the G(0) effects of BCL2 or BCL-x(L), suggesting that mechanisms in
      addition to anti-apoptosis are involved in the cell cycle arrest function of BCL2
      or BCL-x(L). We found that BCL2 and BCL-x(L) expression in bax(-/-) bak(-/-)
      cells did not confer cell cycle effects, consistent with the G(0) function of
      BCL2 and BCL-x(L) being mediated through BAX or BAK. Stabilization of p27 in G(0)
      in BCL2 or BCL-x(L) cells was due to phosphorylation of p27 at Ser(10) by the
      kinase Mirk. In bax(-/-) bak(-/-) cells, total p27 and p27 phosphorylated at
      Ser(10) were elevated. Re-expression of BAX in bax(-/-) bak(-/-) cells and
      silencing of BAX and BAK in wild type cells confirmed that endogenous BAX and BAK
      modulated p27. These data revealed a novel role for BAX and BAK in the regulation
      of G(0) quiescence.

PMID- 18818204
TI  - NblA, a key protein of phycobilisome degradation, interacts with ClpC, a HSP100
      chaperone partner of a cyanobacterial Clp protease.
AB  - When cyanobacteria are starved for nitrogen, expression of the NblA protein
      increases and thereby induces proteolytic degradation of phycobilisomes, light
      harvesting complexes of pigmented proteins. Phycobilisome degradation leads to a
      color change of the cells from blue-green to yellow-green, referred to as
      bleaching or chlorosis. As reported previously, NblA binds via a conserved region
      at its C terminus to the alpha-subunits of phycobiliproteins, the main components
      of phycobilisomes. We demonstrate here that a highly conserved stretch of amino
      acids in the N-terminal helix of NblA is essential for protein function in vivo.
      Affinity purification of glutathione S-transferase-tagged NblA, expressed in a
      Nostoc sp. PCC7120 mutant lacking wild-type NblA, resulted in co-precipitation of
      ClpC, encoded by open reading frame alr2999 of the Nostoc chromosome. ClpC is a
      HSP100 chaperone partner of the Clp protease. ATP-dependent binding of NblA to
      ClpC was corroborated by in vitro pull-down assays. Introducing amino acid
      exchanges, we verified that the conserved N-terminal motif of NblA mediates the
      interaction with ClpC. Further results indicate that NblA binds phycobiliprotein
      subunits and ClpC simultaneously, thus bringing the proteins into close
      proximity. Altogether these results suggest that NblA may act as an adaptor
      protein that guides a ClpC.ClpP complex to the phycobiliprotein disks in the rods
      of phycobilisomes, thereby initiating the degradation process.

PMID- 18818205
TI  - Structures of human host defense cathelicidin LL-37 and its smallest
      antimicrobial peptide KR-12 in lipid micelles.
AB  - As a key component of the innate immunity system, human cathelicidin LL-37 plays
      an essential role in protecting humans against infectious diseases. To elucidate
      the structural basis for its targeting bacterial membrane, we have determined the
      high quality structure of (13)C,(15)N-labeled LL-37 by three-dimensional triple
      resonance NMR spectroscopy, because two-dimensional (1)H NMR did not provide
      sufficient spectral resolution. The structure of LL-37 in SDS micelles is
      composed of a curved amphipathic helix-bend-helix motif spanning residues 2-31
      followed by a disordered C-terminal tail. The helical bend is located between
      residues Gly-14 and Glu-16. Similar chemical shifts and (15)N nuclear Overhauser
      effect (NOE) patterns of the peptide in complex with
      dioctanoylphosphatidylglycerol (D8PG) micelles indicate a similar structure. The
      aromatic rings of Phe-5, Phe-6, Phe-17, and Phe-27 of LL-37, as well as
      arginines, showed intermolecular NOE cross-peaks with D8PG, providing direct
      evidence for the association of the entire amphipathic helix with anionic lipid
      micelles. The structure of LL-37 serves as a model for understanding the
      structure and function relationship of homologous primate cathelicidins. Using
      synthetic peptides, we also identified the smallest antibacterial peptide KR-12
      corresponding to residues 18-29 of LL-37. Importantly, KR-12 displayed a
      selective toxic effect on bacteria but not human cells. NMR structural analysis
      revealed a short three-turn amphipathic helix rich in positively charged side
      chains, allowing for effective competition for anionic phosphatidylglycerols in
      bacterial membranes. KR-12 may be a useful peptide template for developing novel
      antimicrobial agents of therapeutic use.

PMID- 18818206
TI  - Down-regulation of micro-RNA-1 (miR-1) in lung cancer. Suppression of tumorigenic
      property of lung cancer cells and their sensitization to doxorubicin-induced
      apoptosis by miR-1.
AB  - Micro-RNAs are approximately 21-25-nucleotide-long noncoding RNAs that regulate
      gene expression primarily at the post-transcriptional level in animals. Here, we
      report that micro-RNA-1 (miR-1), abundant in the cardiac and smooth muscles, is
      expressed in the lung and is down-regulated in human primary lung cancer tissues
      and cell lines. In situ hybridization demonstrated localization of miR-1 in
      bronchial epithelial cells. The tumor suppressor C/EBPalpha, frequently
      suppressed in lung cancer, reactivated miR-1 expression in the lung cancer cells.
      Repressed miR-1 was also activated in lung cancer cells upon treatment with a
      histone deacetylase inhibitor. These observations led us to examine the
      antitumorigenic potential of miR-1 in lung cancer cells. Expression of miR-1 in
      nonexpressing A549 and H1299 cells reversed their tumorigenic properties, such as
      growth, replication potential, motility/migration, clonogenic survival, and tumor
      formation in nude mice. Exogenous miR-1 significantly reduced expression of
      oncogenic targets, such as MET, a receptor tyrosine kinase, and Pim-1, a Ser/Thr
      kinase, frequently up-regulated in lung cancer. Similarly, the levels of two
      additional targets, FoxP1, a transcription factor with oncogeneic property, and
      HDAC4 that represses differentiation-promoting genes, were reduced in miR-1
      expressing cells. Conversely, depletion of miR-1 facilitated N417 cell growth
      with concomitant elevation of these targets. Further, ectopic miR-1 induced
      apoptosis in A549 cells in response to the potent anticancer drug doxorubicin.
      Enhanced activation of caspases 3 and 7, cleavage of their substrate PARP-1, and
      depletion of anti-apoptotic Mcl-1 contributed to the sensitivity of miR-1
      expressing cells to doxorubicin. Thus, miR-1 has potential therapeutic
      application against lung cancers.

PMID- 18818207
TI  - On the pH regulation of plant aquaporins.
AB  - The majority of plants are unable to evade unfavorable conditions such as
      flooding, salinity, or drought. Therefore, a fine-tuned water homeostasis appears
      to be of crucial importance for plant survival, and it was assumed that
      aquaporins play a significant role in these processes. Regulation of plant
      aquaporin conductivity was suggested to be achieved by a gating mechanism that
      involves protein phosphorylation under drought stress conditions and protonation
      after cytosolic acidification during flooding. The effect of protein
      phosphorylation or protonation of aquaporins was studied on two plasma membrane
      intrinsic proteins, NtPIP2;1 and NtAQP1 from tobacco, which were heterologously
      expressed in yeast. Our results on mutated aquaporins with serine-to-alanine
      exchange indicate that phosphorylation of the two key serine residues did not
      affect the pH-dependent modification of water permeability. Protonation on a
      conserved histidine residue decreased water conductivity of NtPIP2;1. Although
      cells expressing NtPIP2;1 with a replacement of the histidine by an alanine were
      found to be pH-insensitive with regard to water permeability, these maintain high
      water transport rates, similar to those obtained under acidic conditions. The
      data clearly support the role of histidine at 196 as a component of pH-dependent
      modification of aquaporin-facilitated water transport. The predictions of
      combined effects from phosphorylation at conserved serines and histidine
      protonation were not supported by the results of functional analysis. The
      obtained results challenge the gating model as a general regulation mechanism for
      plant plasma membrane aquaporins.

PMID- 18818208
TI  - JNK-mediated phosphorylation of paxillin in adhesion assembly and tension-induced
      cell death by the adenovirus death factor E4orf4.
AB  - The adenovirus type 2 Early Region 4 ORF4 (E4orf4) protein induces a caspase
      independent death program in tumor cells involving changes in actin dynamics that
      are functionally linked to cell killing. Because an increase in myosin II-based
      contractility is needed for the death of E4orf4-expressing cells, we have
      proposed that alteration of cytoskeletal tension is part of the signals engaging
      the death pathway. Yet the mechanisms involved are poorly defined. Herein, we
      show that the Jun N-terminal kinase JNK is activated in part through a pathway
      involving Src, Rho, and ROCK (Rho kinase) and contributes to dysregulate adhesion
      dynamics and to kill cells in response to E4orf4. JNK supports the formation of
      atypically robust focal adhesions, which are bound to the assembly of the
      peculiar actomyosin network typifying E4orf4-induced cell death and which are
      required for driving nuclear condensation. Remarkably, the dramatic enlargement
      of focal adhesions, actin remodeling, and cell death all rely on paxillin
      phosphorylation at Ser-178, which is induced by E4orf4 in a JNK-dependent way.
      Furthermore, we found that Ser-178-paxillin phosphorylation is necessary to
      decrease adhesion turnover and to enhance the time residency of paxillin at focal
      adhesions, promoting its recruitment from an internal pool. Our results indicate
      that perturbation of tensional homeostasis by E4orf4 involves JNK-regulated
      changes in paxillin adhesion dynamics that are required to engage the death
      pathway. Moreover, our findings support a role for JNK-mediated paxillin
      phosphorylation in adhesion growth and stabilization during tension signaling.

PMID- 18818209
TI  - Mitophagy in yeast occurs through a selective mechanism.
AB  - The regulation of mitochondrial degradation through autophagy is expected to be a
      tightly controlled process, considering the significant role of this organelle in
      many processes ranging from energy production to cell death. However, very little
      is known about the specific nature of the degradation process. We developed a new
      method to detect mitochondrial autophagy (mitophagy) by fusing the green
      fluorescent protein at the C terminus of two endogenous mitochondrial proteins
      and monitored vacuolar release of green fluorescent protein. Using this method,
      we screened several atg mutants and found that ATG11, a gene that is essential
      only for selective autophagy, is also essential for mitophagy. In addition, we
      found that mitophagy is blocked even under severe starvation conditions, if the
      carbon source makes mitochondria essential for metabolism. These findings suggest
      that the degradation of mitochondria is a tightly regulated process and that
      these organelles are largely protected from nonspecific autophagic degradation.

PMID- 18818210
TI  - Ziram causes dopaminergic cell damage by inhibiting E1 ligase of the proteasome.
AB  - The etiology of Parkinson disease (PD) is unclear but may involve environmental
      toxins such as pesticides leading to dysfunction of the ubiquitin proteasome
      system (UPS). Here, we measured the relative toxicity of ziram (a UPS inhibitor)
      and analogs to dopaminergic neurons and examined the mechanism of cell death. UPS
      (26 S) activity was measured in cell lines after exposure to ziram and related
      compounds. Dimethyl- and diethyldithiocarbamates including ziram were potent UPS
      inhibitors. Primary ventral mesencephalic cultures were exposed to ziram, and
      cell toxicity was assessed by staining for tyrosine hydroxylase (TH) and NeuN
      antigen. Ziram caused a preferential damage to TH+ neurons and elevated alpha
      synuclein levels but did not increase aggregate formation. Mechanistically, ziram
      altered UPS function through interfering with the targeting of substrates by
      inhibiting ubiquitin E1 ligase. Sodium dimethyldithiocarbamate administered to
      mice for 2 weeks resulted in persistent motor deficits and a mild reduction in
      striatal TH staining but no nigral cell loss. These results demonstrate that
      ziram causes selective dopaminergic cell damage in vitro by inhibiting an
      important degradative pathway implicated in the etiology of PD. Chronic exposure
      to widely used dithiocarbamate fungicides may contribute to the development of
      PD, and elucidation of its mechanism would identify a new potential therapeutic
      target.

PMID- 18818211
TI  - Specific TRPC6 channel activation, a novel approach to stimulate keratinocyte
      differentiation.
AB  - The protective epithelial barrier in our skin undergoes constant regulation,
      whereby the balance between differentiation and proliferation of keratinocytes
      plays a major role. Impaired keratinocyte differentiation and proliferation are
      key elements in the pathophysiology of several important dermatological diseases,
      including atopic dermatitis and psoriasis. Ca(2+) influx plays an essential role
      in this process presumably mediated by different transient receptor potential
      (TRP) channels. However, investigating their individual role was hampered by the
      lack of specific stimulators or inhibitors. Because we have recently identified
      hyperforin as a specific TRPC6 activator, we investigated the contribution of
      TRPC6 to keratinocyte differentiation and proliferation. Like the endogenous
      differentiation stimulus high extracellular Ca(2+) concentration ([Ca(2+)](o)),
      hyperforin triggers differentiation in HaCaT cells and in primary cultures of
      human keratinocytes by inducing Ca(2+) influx via TRPC6 channels and additional
      inhibition of proliferation. Knocking down TRPC6 channels prevents the induction
      of Ca(2+)- and hyperforin-induced differentiation. Importantly, TRPC6 activation
      is sufficient to induce keratinocyte differentiation similar to the physiological
      stimulus [Ca(2+)](o). Therefore, TRPC6 activation by hyperforin may represent a
      new innovative therapeutic strategy in skin disorders characterized by altered
      keratinocyte differentiation.

PMID- 18818212
TI  - Impact of advanced age on survival in patients with implantable cardioverter
      defibrillators.
AB  - AIMS: Given the selectivity of clinical trial patients and meager representation
      of elderly in the major implantable cardioverter defibrillator (ICD) randomized
      trials (<25%), whether such data apply to elderly patients overall is unclear.
      The purpose of our study is to understand the influence of age on mortality after
      ICD implantation. METHODS AND RESULTS: We performed a retrospective cohort study
      of 502 consecutive patients receiving ICDs from 1993 to 2003 at a single
      university hospital. The primary predictor was patient age, categorized as <65,
      65-75, and >75 years at ICD implantation. The primary outcome was time to death.
      Mean follow-up was 4 years. Median survival after ICD implantation was 5.3 years
      among subjects >75 years, less than half that of the youngest group. After
      adjusting for potential confounders, compared with subjects <65 years of age,
      patients >75 years [hazard ratio (HR), 4.7; 95% confidence interval (CI), 2.8
      7.9; P < 0.001] and those 65-75 years (HR, 2.8; 95% CI, 1.7-4.8; P < 0.001) were
      at greater risk of death. Increased age was associated with higher total,
      cardiac, and non-cardiac mortality (all P <or= 0.001). CONCLUSION: Age at ICD
      implantation is strongly and independently associated with mortality. Age should
      be considered among potential co-morbidities in anticipating survival of the
      elderly patient prior to ICD implantation.

PMID- 18818213
TI  - The origin of post-injury neointimal cells in the rat balloon injury model.
AB  - AIMS: The origin of post-injury neointimal cells is still a matter of debate.
      This study aims to determine the anatomic source of neointimal cells in one of
      the most important animal models for the study of vascular stenosis in response
      to injury, the rat balloon injury model. METHODS AND RESULTS: Chimeric rats were
      generated by rescuing lethally irradiated animals with green fluorescent protein
      (GFP)(+) bone marrow (BM) cells from transgenic rats. Neointimal formation was
      induced in the right iliac artery of these animals using a balloon angioplasty
      catheter. Injured and non-injured contra-lateral arteries were harvested at 7,
      14, and 30 days post-surgery. BM-derived monocytes/macrophages (CD68(+) GFP(+))
      were abundant in the media and adventitia of injured vessels harvested at 7 days
      as determined by immunofluorescence and confocal microscopy. The number of GFP(+)
      cells declined in the vascular wall with time. Post-injury neointimal cells were
      mostly GFP(-)/smooth muscle actin (SMA)(+), which indicated that those cells
      originated in the recipient. Only a few neointimal cells seemed to come from
      circulating progenitors (GFP(+) SMA(+), 2.34% +/- 1.61). The vascular origin of
      cells in the neointima was further confirmed by transplanting injured GFP
      arteries into wild-type recipients. In these grafts, 94.23 +/- 0.44% of medial
      and 92.95 +/- 19.34% of neointimal cells were GFP(+) SMA(+). Finally, we tested
      the capacity of vascular smooth muscle cells (VSMC) to migrate through the
      vascular wall using a novel in vivo assay. As expected, VSMC migrated and
      populated the neointima only in response to injury. CONCLUSION: Our results
      suggest that neointimal cells in the rat balloon injury model mostly derive from
      pre-existing vascular cells and that only a small population of those cells come
      from BM-derived progenitors.

PMID- 18818214
TI  - CD4+ CD28 null T cells in coronary artery disease: when helpers become killers.
AB  - The crucial role of T cells in atherosclerosis and coronary artery disease (CAD)
      has been highlighted by recent observations. Helper CD4(+) T cells can both
      aggravate or attenuate the atherogenic process and the development of CAD.
      CD4(+)CD28(null) T cells are an unusual subset of helper cells which expand and
      have deleterious effects in CAD. In this review, we discuss the current issues on
      the generation of CD4(+)CD28(null) T cells and focus on their phenotypic and
      functional characteristics relevant to the development of cardiovascular events.
      The possible effects of the present day therapies for CAD on the CD4(+)CD28(null)
      T cells are also explored. Targeting the CD4(+)CD28(null) T cell subset in CAD
      could provide novel therapeutic strategies to prevent acute life-threatening
      coronary events.

PMID- 18818215
TI  - Searching protein structure databases with DaliLite v.3.
AB  - The Red Queen said, 'It takes all the running you can do, to keep in the same
      place.' Lewis Carrol MOTIVATION: Newly solved protein structures are routinely
      scanned against structures already in the Protein Data Bank (PDB) using Internet
      servers. In favourable cases, comparing 3D structures may reveal biologically
      interesting similarities that are not detectable by comparing sequences. The
      number of known structures continues to grow exponentially. Sensitive-thorough
      but slow-search algorithms are challenged to deliver results in a reasonable
      time, as there are now more structures in the PDB than seconds in a day. The
      brute-force solution would be to distribute the individual comparisons on a
      massively parallel computer. A frugal solution, as implemented in the Dali
      server, is to reduce the total computational cost by pruning search space using
      prior knowledge about the distribution of structures in fold space. This note
      reports paradigm revisions that enable maintaining such a knowledge base up-to
      date on a PC. AVAILABILITY: The Dali server for protein structure database
      searching at http://ekhidna.biocenter.helsinki.fi/dali_server is running DaliLite
      v.3. The software can be downloaded for academic use from
      http://ekhidna.biocenter.helsinki.fi/dali_lite/downloads/v3.

PMID- 18818216
TI  - Bayesian learning of biological pathways on genomic data assimilation.
AB  - MOTIVATION: Mathematical modeling and simulation, based on biochemical rate
      equations, provide us a rigorous tool for unraveling complex mechanisms of
      biological pathways. To proceed to simulation experiments, it is an essential
      first step to find effective values of model parameters, which are difficult to
      measure from in vivo and in vitro experiments. Furthermore, once a set of
      hypothetical models has been created, any statistical criterion is needed to test
      the ability of the constructed models and to proceed to model revision. RESULTS:
      The aim of our research is to present a new statistical technology towards data
      driven construction of in silico biological pathways. The method starts with a
      knowledge-based modeling with hybrid functional Petri net. It then proceeds to
      the Bayesian learning of model parameters for which experimental data are
      available. This process exploits quantitative measurements of evolving
      biochemical reactions, e.g. gene expression data. Another important issue that we
      consider is statistical evaluation and comparison of the constructed hypothetical
      pathways. For this purpose, we have developed a new Bayesian information
      theoretic measure that assesses the predictability and the biological robustness
      of in silico pathways. AVAILABILITY: The FORTRAN source codes are available at
      the URL http://daweb.ism.ac.jpyoshidar/GDA/ SUPPLEMENTARY INFORMATION:
      Supplementary data are available at Bioinformatics online.

PMID- 18818217
TI  - Improving 2D-DIGE protein expression analysis by two-stage linear mixed models:
      assessing experimental effects in a melanoma cell study.
AB  - MOTIVATION: Difference in-gel electrophoresis (DIGE)-based protein expression
      analysis allows assessing the relative expression of proteins in two biological
      samples differently labeled (Cy5, Cy3 CyDyes). In the same gel, a reference
      sample is also used (Cy2 CyDye) for spot matching during image analysis and
      volume normalization. The standard statistical techniques to identify
      differentially expressed (DE) proteins are the calculation of fold-changes and
      the comparison of treatment means by the t-test. The analyses rarely accounts for
      other experimental effects, such as CyDye and gel effects, which could be
      important sources of noise while detecting treatment effects. RESULTS: We propose
      to identify DIGE DE proteins using a two-stage linear mixed model. The proposal
      consists of splitting the overall model for the measured intensity into two
      interconnected models. First, we fit a normalization model that accounts for the
      general experimental effects, such as gel and CyDye effects as well as for the
      features of the associated random term distributions. Second, we fit a model that
      uses the residuals from the first step to account for differences between
      treatments in protein-by-protein basis. The modeling strategy was evaluated using
      data from a melanoma cell study. We found that a heteroskedastic model in the
      first stage, which also account for CyDye and gel effects, best normalized the
      data, while allowing for an efficient estimation of the treatment effects. The
      Cy2 reference channel was used as a covariate in the normalization model to avoid
      skewness of the residual distribution. Its inclusion improved the detection of DE
      proteins in the second stage.

PMID- 18818218
TI  - Acute retinal pigment epithelial detachment secondary to pamidronate
      administration.
AB  - Bisphosphonates are associated with an important number of inflammatory ocular
      side-effects including but not limited to conjunctivitis, episcleritis,
      scleritis, uveitis, and optic neuritis. The intravenous bisphosphonates appear to
      be linked with more severe ocular inflammation than the orally administered ones.
      These eye complications tend to resolve with the bisphosphonate discontinuation
      and can re-occur with its re-challenge. We present here the first case of an
      acute retinal pigment epithelial detachment associated with pamidronate infusion
      in a 59-year-old patient with metastatic prostate cancer.

PMID- 18818219
TI  - The management of prolonged, isolated hyperbilirubinemia following cytarabine
      based chemotherapy for acute myeloid leukaemia.
AB  - BACKGROUND: Patients diagnosed with Acute Myeloid Leukaemia (AML) often receive
      cytarabine-based chemotherapy as standard treatment. Cytarabine is usually given
      in combination with other agents such as idarubicin. Such treatments are known to
      cause hepatic dysfunction characterized by a combination of jaundice,
      hyperbilirubinemia and increases in liver enzymes. Isolated hyperbilirubinemia is
      rarely reported. It is often difficult to identify a causative agent for the
      hepatic dysfunction, as there are often complicating factors such as sepsis. AIM:
      To report a case of isolated hyperbilirubinemia in a patient treated with
      cytarabine-based chemotherapy for AML. CLINICAL DETAILS: After a diagnosis of AML
      the patient was admitted to hospital to receive induction chemotherapy consisting
      of high-dose cytarabine, idarubicin, and etoposide. All baseline laboratory
      results were normal, except the full blood evaluation that was consistent with
      AML. The chemotherapy was delivered over 7 days, and on the eighth day the
      patient had a bilirubin (BL) level of 27 micromol/L(normal range 522 micromol/L).
      All other liver function tests (LFT) were normal. This isolated
      hyperbilirubinemia remained for the rest of the patient's admission, peaking on
      day 26, with a level of 255 micromol/L. After a stay in the intensive care unit,
      the patient was discharged on day 45 with a bilirubin level of 33 micromol/L. All
      other LFT remained unremarkable. OUTCOME: The isolated hyperbilirubinemia
      resolved slowly and on day 68, when the patient was re-admitted for further dose
      reduced cytarabine, the BL level was 21 micromol/L. The patient was successfully
      retreated with this lower dose regimen. CONCLUSION: Isolated hyperbilirubinemia
      is an uncommon presentation of cytarabine induced liver dysfunction. Resolution
      does occur but over a prolonged period. A lower dose of cytarabine for future
      treatment should be considered.

PMID- 18818220
TI  - Oncology medication safety: a 3D status report 2008.
AB  - BACKGROUND: The safe use of medications is a major concern in oncology practice.
      Three organizations collaborated on a survey to determine if practitioners had
      implemented current recommended safe practices for IV vincristine administration,
      general oncology safe practices, and safe practices for oral chemotherapy.
      METHODS: A survey was distributed to members of the Hematology Oncology Pharmacy
      Association (HOPA) and the International Society of Pharmacy Practitioners
      (ISOPP) using Survey Monkey. The Institute of Safe Medication Practices (ISMP)
      also solicited readers of its Medication Safety Alert! to respond to the survey.
      A comparison to results from a survey conducted by ISMP in 2006 on safe practices
      for IV vincristine was also conducted. RESULTS: The majority of respondents were
      aware of the WHO recommendations for IV vincristine, although the rate of
      implementation of the guidelines ranged from 24.1 to 53.6%. When compared to the
      ISMP 2006 survey there was a 25.8-37.4% improvement in following many of the safe
      practice guidelines. Administering IV vincristine via a minibag showed the lowest
      rate of adoption (less than 40%). Of the 35 survey items on general chemotherapy
      safety strategies, 80% of respondents had implemented at least 21 items in the
      survey. Overall 32.4% of respondents did not consider oral chemotherapy as
      requiring the same safety concerns as parenteral therapy. CONCLUSIONS: The
      results of this survey will provide a new baseline for the adoption rate of safe
      medication practice recommendations related to oncology. Further work on
      addressing barriers in adopting identified safe practice recommendations needs to
      be conducted.

PMID- 18818221
TI  - On playing the Nazi card.

PMID- 18818222
TI  - "Nicotine Nazis strike again": a brief analysis of the use of Nazi rhetoric in
      attacking tobacco control advocacy.

PMID- 18818225
TI  - Signed, sealed and delivered: "big tobacco" in Hollywood, 1927-1951.
AB  - OBJECTIVE: Smoking in movies is associated with adolescent and young adult
      smoking initiation. Public health efforts to eliminate smoking from films
      accessible to youth have been countered by defenders of the status quo, who
      associate tobacco imagery in "classic" movies with artistry and nostalgia. The
      present work explores the mutually beneficial commercial collaborations between
      the tobacco companies and major motion picture studios from the late 1920s
      through the 1940s. METHODS: Cigarette endorsement contracts with Hollywood stars
      and movie studios were obtained from internal tobacco industry documents at the
      University of California, San Francisco (UCSF) Legacy Tobacco Documents Library
      and the Jackler advertising collection at Stanford. RESULTS: Cigarette
      advertising campaigns that included Hollywood endorsements appeared from 1927 to
      1951, with major activity in 1931-2 and 1937-8 for American Tobacco Company's
      Lucky Strike, and in the late 1940s for Liggett & Myers' Chesterfield.
      Endorsement contracts and communication between American Tobacco and movie stars
      and studios explicitly reveal the cross-promotional value of the campaigns.
      American Tobacco paid movie stars who endorsed Lucky Strike cigarettes US$218,750
      in 1937-8 (equivalent to US$3.2 million in 2008) for their testimonials.
      CONCLUSIONS: Hollywood endorsements in cigarette advertising afforded motion
      picture studios nationwide publicity supported by the tobacco industry's
      multimillion US dollar advertising budgets. Cross-promotion was the incentive
      that led to a synergistic relationship between the US tobacco and motion picture
      industries, whose artefacts, including "classic" films with smoking and glamorous
      publicity images with cigarettes, continue to perpetuate public tolerance of
      onscreen smoking. Market-based disincentives within the film industry may be a
      solution to decouple the historical association between Hollywood films and
      cigarettes.

PMID- 18818226
TI  - Smuggling as the "key to a combined market": British American Tobacco in Lebanon.
AB  - OBJECTIVES: To understand the strategy of British American Tobacco (BAT) and
      other transnational tobacco companies (TTCs) to gain access to the Lebanese
      market, which has remained relatively closed under monopoly ownership and
      political instability. METHODS: Analysis of internal industry documents, local
      language secondary sources and industry publications. RESULTS: TTCs have relied
      on legal and illegal channels to supply the Lebanese market since at least the
      1970s. Available documents suggest smuggling has been an important component of
      BAT's market entry strategy, transported in substantial quantities via middlemen
      for sale in Lebanon and neighbouring countries. TTCs took advantage of weak and
      unstable governance, resulting in uncertainty over the Regie's legal status, and
      continued to supply the contraband trade despite appeals by the government to
      cease undermining its revenues. Since the end of the civil war in the early
      1990s, continued uncertainty about the tobacco monopoly amid political
      instability has encouraged TTCs to seek a legal presence in the country, while
      continuing to achieve substantial sales through contraband. CONCLUSION: Evidence
      of the complicity of TTCs in cigarette smuggling extends to Lebanon and the
      Middle East where this trade has especially benefited from weak governance and
      chronic political instability. The regional nature of TTC strategy supports
      strong international cooperation under the Framework Convention on Tobacco
      Control to tackle the problem.

PMID- 18818228
TI  - A functional Ser(413)/Ser(413) PAI-2 polymorphism is associated with
      susceptibility and damage index score in systemic lupus erythematosus.
AB  - Systemic lupus erythematosus in some cases is characterized for development of
      thrombotic events with a significantly increased risk of mortality. The
      frequencies and clinical associations of Ser(413)/Cys(413) PAI-2 polymorphism in
      40 systemic lupus erythematosus, 50 rheumatoid arthritis patients, and 100
      healthy subjects were investigated. The Ser(413)/Ser(413) genotype frequency was
      53% (lupus), 36% (rheumatoid arthritis), and 35% (healthy subjects). The Ser(413)
      allele was associated with systemic lupus erythematosus (P = .04, odds ratio =
      1.76, 95% confidence interval = 1.01-3.06). In all, 4 patient carriers of
      Ser(413)/Ser(413) genotype, developed thrombotic events. The lupus patients
      identified with Ser( 413)/Ser(413) genotype showed an increased damage (57%),
      compared with Ser(413)/Cys(413) and Cys(413)/Cys(413) genotypes, with significant
      difference (P = .03). These findings suggest an association of Ser( 413) /Ser(
      413) genotype with greater damage index score and Ser( 413) allele with systemic
      lupus erythematosus. Besides, PAI-2 polymorphism could be related with thrombotic
      phenomena in systemic lupus erythematosus.

PMID- 18818229
TI  - Should plasma homocysteine be used as a biomarker of venous thromboembolism? A
      case-control study.
AB  - Mild or moderate hyperhomocysteinemia as a risk factor for venous thrombosis is
      still a matter of debate. The strength of this study is to bring a body of
      elements to evaluate whether hyperhomocysteinemia should be used as a biomarker
      for venous thromboembolism (VTE). These elements consist of a biological
      evaluation of several hematological risk factors, and an original control group
      made of patients with a negative Doppler ultrasonography. A total of 151 cases
      and 155 controls were included. Total plasma homocysteine level, MTHFR C677T
      polymorphism, inherited abnormalities of the natural anticoagulant system as well
      as plasma folate and cobalamin levels were determined. A total of 41 (27.2 %) of
      cases and only 9 (5.8%) of controls had at least one of the coagulation defects
      studied. No significant difference was observed for total homocysteine levels
      between the 2 groups: median (interquartile range) = 8.3 (7.2-10.8) micromol/L
      for cases and 8.4 (7-10.9) micromol/L for controls. We found significantly more
      plasma folates and/or cobalamin deficiencies in controls (18.3%) than in cases
      (8.6%). After adjustment for several variables significantly related to risk
      factors of VTE, hyperhomocysteinemia (>13.2 micromol/L) was not found
      statistically associated with VTE: odds ratio 1.36 (95% confidence interval, 0.52
      3.54). The prevalence of the homozygous 677TT polymorphism in the MTHFR gene was
      not increased in cases compared with controls. Mild or moderate
      hyperhomocysteinemia does not seem to be a strong determinant in VTE not only
      when the control group does not exclusively include healthy persons but also in
      investigated disease-free (thromboembolic disease) controls.

PMID- 18818230
TI  - Acute massive pulmonary embolism with hemodynamic compromise treated successfully
      with thrombolytic therapy.
AB  - A 78 year-old woman presented with a history of 15 days of dyspnea and tachypnea
      at rest. A distended right ventricle with free-wall hypokinesis and displacement
      of the interventricular septum toward the left ventricle were shown on
      echocardiography. The patient suddenly arrested. She underwent cardiac
      catheterization and selective pulmonary angiography for suspected pulmonary
      embolism while undergoing cardiopulmonary resuscitation. With the diagnosis of
      pulmonary embolism confirmed, recombinant tissue plasminogen activator was given
      immediately in the catheterization room. This case shows how pulmonary embolism
      can be diagnosed with pulmonary angiography during cardiopulmonary resuscitation
      and the life-saving result from rapid thrombolysis with recombinant tissue
      plasminogen activator.

PMID- 18818231
TI  - Stem cell therapy: a promising and prospective approach in the treatment of
      patients with severe Buerger's disease.
AB  - No effective blood-flow enhancement therapies are available for patients with
      severe peripheral arterial disease (SPAD), thus amputation remains the only
      option for relief of rest pain or gangrene. Autologous bone marrow-derived stem
      cell therapy (ABMSCT) is an emerging modality to induce angiogenesis from
      endothelial progenitors. A total of 5 patients with SPAD were treated by ABMSCT
      using isolated CD34+ cells with characterized phenotype administered by
      intramuscular injections. The follow-up before and 1, 3, 6, 9, and 12 months
      after ABMSCT was based on clinical (rest pain, walking distance without pain,
      nonhealing ulcers, ankle-brachial index [ABI]) and laboratory (angiography,
      duplex and laser ultrasonography, TcPO(2)) parameters. Significant improvement of
      pain and walking distance was observed in all patients. Nonhealing ulcers
      disappeared in 3 patients and became smaller and thinner in 1 patient. The
      average of ABI improved significantly on the treated limb but did not change on
      the contralateral limb. New collaterals were detected by angiography in 3
      patients, but duplex ultrasonography detected improvement in one patient only.
      Laser ultrasonography showed a mild significant change, TcPO(2) values improved
      mainly on the foot. Severe adverse events were not observed. We conclude that
      ABMSCT with isolated CD34+ cells is safe, effective, and results in sustained
      clinical benefit for patients with SPAD.

PMID- 18818232
TI  - A review of the trials comparing carotid endarterectomy and carotid angioplasty
      and stenting.
AB  - In the last decade, carotid artery angioplasty and stenting (CAS) has gained
      popularity as an alternative to carotid endarterectomy (CEA) for the treatment of
      carotid stenosis, particularly in patients who are at high operative risk. CAS
      offers the advantage of being a less invasive procedure, potentially minimizing
      the risks of wound complications and cranial nerve injury, which may translate
      into shorter length of hospitalization and less resource utilization. Since the
      advent of CAS, several randomized controlled trials and carotid stent registry
      trials have been conducted comparing the outcomes of CEA with those of CAS for
      the treatment of carotid stenosis in both symptomatic and asymptomatic patients.
      This review will summarize the results of randomized controlled trials (CAVATAS,
      WALLSTENT, SAPPHIRE, EVA-3S, SPACE, and CaRESS) as well as pivotal carotid
      registry studies (ARCHeR, BEACH, CAPTURE, CASES-PMS, CREATE, and CABernET)
      intended to evaluate the safety and efficacy of CEA and CAS in treatment of
      carotid stenosis. In addition, it will provide a preview of the current ongoing
      and future trials examining the safety, applicability, and indications of CAS and
      CEA (CREST, CAVATAS-2, ACT 1, and TACIT).

PMID- 18818233
TI  - Cell therapy in peripheral arterial disease.
AB  - Management of advanced obstructive vascular disease affecting the extremities
      poses tremendous challenges for physicians and patients. Peripheral arterial
      disease is often a consequence of obstructive atherosclerosis affecting the
      ileofemoral circulation but is also rarely a result of nonatherosclerotic
      conditions such as thromboangiitis obliterans (Buerger's disease). Consequences
      range from the presence of asymptomatic obstruction to intermittent claudication,
      development of rest pain, ulceration, gangrene, and amputation. A relatively new
      and promising approach using cell therapy has recently been developed to treat
      intractable symptoms related to ischemia in subjects with peripheral arterial
      disease in whom conventional medical therapy and revascularization modalities
      have been exhausted.

PMID- 18818234
TI  - Detection of cytomegalovirus in atherosclerotic plaques and nonatherosclerotic
      arteries.
AB  - Several studies have reported an association between infectious agents and
      atherosclerosis. Cytomegalovirus (CMV) is the most commonly implicated viral
      pathogen. However, the role of CMV in atherosclerosis remains obscure. The
      present study evaluated the presence of CMV DNA in atherosclerotic plaques and
      normal vessel walls. A total of 40 arterial specimens from coronary plaques and
      27 samples from normal vessels were obtained from 26 patients who underwent
      aortocoronary bypass surgery. The specimens were analyzed by polymerase chain
      reaction for the presence of the CMV immediate early genomic region. CMV DNA was
      detected in 9 out of 26 patients (34.6%). Viral DNA was detected in both
      nonatherosclerotic tissues and atherosclerotic plaques. No statistically
      significant differences were observed between normal and diseased vessels. Our
      findings, in accordance with previous studies, do not support a direct causative
      role of CMV in the development of atherosclerotic plaques.

PMID- 18818235
TI  - Relationship between aortic atherosclerosis and dental loss in an inner-city
      population.
AB  - Prior studies have suggested an association between atherosclerosis and
      periodontal disease, both of which are more prevalent in certain minority and
      economically disadvantaged groups. Few studies have addressed the relationship
      between cardiovascular disease and dentition among ethnically diverse
      populations. We studied 131 subjects (60% females, age 59 +/- 15 years) who were
      referred for clinically indicated transesophageal echocardiography. Dental loss
      was more severe in patients with hypertension (P < .001), diabetes (P = .05),
      coronary artery disease (P = .04), and calcium channel blocker use (P = .04). On
      univariate analysis, maximal aortic intima-media thickness (MAIMT) was
      significantly correlated with dental loss (r = .40; P < .001). Age was correlated
      with MAIMT (R = .41; P < .001) and with dental loss (r = .57; P < .001). On
      multivariate analysis, dental loss (P = .03) and history of coronary artery
      disease (P = .04) were independent predictors of MAIMT ( R2 = .44). In this inner
      city predominantly African American population, atherosclerosis and dental loss
      are age dependent and are interrelated independent of age.

PMID- 18818236
TI  - Further data about venous catheter fragmentation.

PMID- 18818237
TI  - Risk factors for abdominal aortic aneurysm and the influence of social
      deprivation.
AB  - INTRODUCTION: the objective of this abdominal aortic aneurysm (AAA) screening
      study was to determine attendance and disease prevalence patterns in Northern
      Ireland and the role of deprivation and other risk factors. PATIENTS AND METHODS:
      patients from primary care practices from Belfast, Lisburn, and Saintfield were
      screened. Past medical history and deprivation details were determined. RESULTS:
      2264 men from Belfast, 1104 men in Lisburn, and 284 in Saintfield were invited to
      attend. Overall, 1659 (45.3%) men attended, with 40.6% from Belfast, 55.0% from
      Lisburn, and 45.8% from Saintfield (P < .0001). Ninety-two (5.5%) new AAAs were
      diagnosed, with 6.5%, 3.8%, and 6.2% in the 3 areas (P = .055). As deprivation
      decreased, attendance increased and prevalence decreased. Smoking, peripheral
      arterial disease, number of medications prescribed, and geographical origin were
      independent risk factors for AAAs. CONCLUSION: aneurysm prevalence is influenced
      by geographical origin and deprivation, which should, therefore, be important
      factors in health care planning and screening provision.

PMID- 18818238
TI  - Statin contraindicated in heart failure.

PMID- 18818239
TI  - Predictors of long-term major adverse cardiac events and clinical restenosis
      following elective percutaneous coronary stenting.
AB  - Limited data exist regarding the predictors of long-term clinical outcomes
      following elective percutaneous coronary intervention (PCI) in the current era of
      stenting. The authors investigated the predictors of major adverse cardiac events
      (MACE) and clinical restenosis in 740 consecutive patients who underwent
      successful elective PCI with bare metal stents (BMSs) or drug-eluting stents
      (DESs). At 30-month follow-up, compared with BMS recipients, DES recipients had a
      significantly lower rate of MACE, which was mainly driven by a decreased repeat
      target vessel PCI. The rate of 30-month clinical restenosis was significantly
      lower in DES recipients. The authors conclude that baseline clinical,
      angiographic, and procedural characteristics determine long-term MACE and
      clinical restenosis after elective PCI, with DES being the independent predictor
      for both.

PMID- 18818240
TI  - Benefits of low-intensity pain-free treadmill exercise on functional capacity of
      individuals presenting with intermittent claudication due to peripheral arterial
      disease.
AB  - Patients with intermittent claudication due to peripheral arterial disease (PAD)
      experience muscle aching during walking secondary to ischemia. The purpose of
      this study was to examine the effects of low-intensity pain-free exercise (LIPFE)
      on functional capacity of individuals with PAD. A total of 12 participants with
      PAD underwent training on treadmill for 6 weeks, twice a week, for about 45
      minutes. Outcome measures included walking distance (WDI), walking duration
      (WDU), mean walking rate (WR), estimated oxygen consumption (EVO(2)), metabolic
      equivalent (MET), estimated total energy expenditure (ETEE), and estimated rate
      of energy expenditure (EREE). Mean improvement of WDI, WDU, and MWR were 104% (an
      addition of 1.0 km), 55% (an addition of 13.3 minutes), and 41% (0.9 km/h
      faster), respectively. Mean improvement of EVO(2), MET, ETEE, and EREE, were 20%,
      20%, 80%, and 20%, respectively. In conclusion, it appears that LIPFE training is
      an effective intervention for individuals presenting with PAD.

PMID- 18818241
TI  - A potential role for Akt/FOXO signalling in both protein loss and the impairment
      of muscle carbohydrate oxidation during sepsis in rodent skeletal muscle.
AB  - Sepsis causes muscle atrophy and insulin resistance, but the underlying
      mechanisms are unclear. Therefore, the present study examined the effects of
      lipopolysaccharide (LPS)-induced endotoxaemia on the expression of Akt, Forkhead
      Box O (FOXO) and its downstream targets, to identify any associations between
      changes in FOXO-dependent processes influencing muscle atrophy and insulin
      resistance during sepsis. Chronically instrumented male Sprague-Dawley rats
      received a continuous intravenous infusion of LPS (15 microg kg(-1) h(-1)) or
      saline for 24 h at 0.4 ml h(-1). Animals were terminally anaesthetized and the
      extensor digitorum longus muscles from both hindlimbs were removed and snap
      frozen. Measurements were made of mRNA and protein expression of selected
      signalling molecules associated with pathways regulating protein synthesis and
      degradation and carbohydrate metabolism. LPS infusion induced increases in muscle
      tumour necrosis factor-alpha (8.9-fold, P < 0.001) and interleukin-6 (8.4-fold, P
      < 0.01), paralleled by reduced insulin receptor substrate-1 mRNA expression (-0.7
      fold, P < 0.01), and decreased Akt1 protein and cytosolic FOXO1 and FOXO3
      phosphorylation. These changes were accompanied by significant increases in
      muscle atrophy F-box mRNA (5.5-fold, P < 0.001) and protein (2-fold, P < 0.05)
      expression, and pyruvate dehydrogenase kinase 4 mRNA (15-fold, P < 0.001) and
      protein (1.6-fold, P < 0.05) expression. There was a 29% reduction in the muscle
      protein: DNA ratio, a 56% reduction in pyruvate dehydrogenase complex (PDC)
      activity (P < 0.05), and increased glycogen degradation and lactate accumulation.
      The findings of this study suggest a potential role for Akt/FOXO in the
      simultaneous impairment of carbohydrate oxidation, at the level of PDC, and up
      regulation of muscle protein degradation, in LPS-induced endotoxaemia.

PMID- 18818242
TI  - Expression of the SK2 calcium-activated potassium channel is required for
      cholinergic function in mouse cochlear hair cells.
AB  - Efferent inhibition of cochlear hair cells is mediated by 'nicotinic' cholinergic
      receptors functionally coupled to calcium-activated, small conductance (SK2)
      potassium channels. We recorded from cochlear hair cells in SK2 knockout mice to
      evaluate further the role of this channel in efferent function. Since cholinergic
      inhibitory synapses can be found on inner or outer hair cells, depending on
      developmental age, both cell types were studied. To determine if SK channel
      activity was indeed eliminated, seconds-long voltage-gated calcium influx was
      used to activate slowly rising and falling calcium-dependent potassium currents.
      These were identified as SK currents by their time course, calcium dependence and
      sensitivity to block by apamin in wild-type IHCs. IHCs from knockout mice had no
      SK current by these same criteria. Thus, the SK2 gene is solely responsible for
      encoding the SK channels of inner hair cells. Other aspects of hair cell
      excitability remained relatively unaffected. Unexpectedly, cholinergic synaptic
      currents were entirely absent from both inner and outer SK2-knockout hair cells.
      Further, direct application of ACh caused no change in membrane current, implying
      absent or otherwise dysfunctional ACh receptors. Immunohistology of whole-mounts
      using the antibody to the synaptic vesicle protein 2 (SV2) revealed a pronounced
      reduction of efferent innervation to outer hair cells (OHCs) in the knockout
      cochleas. Quantitative RT-PCR analysis, however, showed no change in the mRNA
      levels of alpha9 and alpha10 nicotinic ACh receptor (nAChR) genes. Thus, some
      aspect of translation or subsequent protein processing leads to non-functional or
      absent ACh receptors. These results indicate that SK2 channels are required both
      for expression of functional nAChRs, and for establishment and/or maintenance of
      efferent terminals in the cochlea.

PMID- 18818243
TI  - Saliva production and surface tension: influences on patency of the passive upper
      airway.
AB  - Pharyngeal patency is influenced by the surface tension (gamma) of the upper
      airway lining liquid (UAL), of which saliva is a major component. We investigated
      the influences of saliva production on gamma of the UAL, and upper airway re
      opening and closing pressures. In 10 supine, male, anaesthetized,
      tracheostomised, mechanically ventilated New Zealand White rabbits, we measured
      re-opening and closing of the passive isolated upper airway at baseline and
      following graded (cumulative) doses of methacholine or atropine. Upper airway
      liquid volume index (UALVI) was assessed using a standardized suction procedure
      (secretion weight obtained per second) expressed as the natural logarithm
      (LnUALVI). The gamma of UAL samples were measured using the 'pull-off' force
      technique. Across all animals, baseline values were: LnUALVI -6.2 (-8.6 to -5.4)
      median (interquartile range), gamma of UAL 58.9 (56.6-59.9) mN m(-1), re-opening
      8.6 (6.9-11.1) cmH(2)O, and closing pressures 3.2 (1.8-5.7) cmH(2)O. LnUALVI
      increased by approximately 0.17 per microg kg(-1) methacholine and decreased by
      approximately 0.14 per 100 microg kg(-1) atropine (both P < 0.03, linear mixed
      effects modelling). Surface tension was unchanged by methacholine but increased
      by approximately 0.6 mN m(-1) per 100 microg kg(-1) atropine (P < 0.004). When
      data were analysed across all animals, both re-opening and closing pressures
      increased as surface tension increased (by approximately 0.4 cmH(2)O mN(-1) and
      by approximately 0.7 cmH(2)O mN(-1), respectively; both P < 0.05). We conclude
      that saliva production influences upper airway mechanical properties partly via
      alterations in gamma of UAL. We speculate that in obstructive sleep apnoea,
      altered autonomic activity may reduce saliva production and increase surface
      tension of the upper airway lining liquid, thus increasing the likelihood of
      upper airway obstruction.

PMID- 18818244
TI  - A critical GxxxA motif in the gamma6 calcium channel subunit mediates its
      inhibitory effect on Cav3.1 calcium current.
AB  - The eight members of the calcium channel gamma subunit family are integral
      membrane proteins that regulate the expression and behaviour of voltage and
      ligand gated ion channels. While a subgroup consisting of gamma(2), gamma(3),
      gamma(4) and gamma(8) (the TARPs) modulate AMPA receptor localization and
      function, the gamma(1) and gamma(6) subunits conform to the original description
      of these proteins as regulators of voltage gated calcium channels. We have
      previously shown that the gamma(6) subunit is highly expressed in atrial myocytes
      and that it is capable of acting as a negative modulator of low voltage activated
      calcium current. In this study we extend our understanding of gamma(6) subunit
      modulation of low voltage activated calcium current. Using engineered chimeric
      constructs, we demonstrate that the first transmembrane domain (TM1) of gamma(6)
      is necessary for its inhibitory effect on Cav3.1 current. Mutational analysis is
      then used to identify a unique GxxxA motif within TM1 that is required for the
      function of the subunit strongly suggesting the involvement of helix-helix
      interactions in its effects. Results from co-immunoprecipitation experiments
      confirm a physical association of gamma(6) with the Cav3.1 channel in both HEK
      cells and atrial myocytes. Single channel analysis reveals that binding of
      gamma(6) reduces channel availability for activation. Taken together, the results
      of this study provide both a molecular and a mechanistic framework for
      understanding the unique ability of the gamma(6) calcium channel subunit to
      modulate low voltage activated (Cav3.1) calcium current density.

PMID- 18818245
TI  - Na+,K+-ATPase is modulated by angiotensin II in diabetic rat kidney--another
      reason for diabetic nephropathy?
AB  - Angiotensin II (ANGII) plays a central role in the enhanced sodium reabsorption
      in early type 1 diabetes in man and in streptozotocin-induced (STZ) diabetic
      rats. This study investigates the effect of untreated STZ-diabetes leading to
      diabetic nephropathy in combination with ANGII treatment, on the abundance and
      localization of the renal Na(+),K(+)-ATPase (NKA), a major contributor of renal
      sodium handling. After 7 weeks of STZ-diabetes (i.v. 65 mg kg(-1)) a subgroup of
      control (C) and diabetic (D7) Wistar rats were treated with ANGII (s.c. minipump
      33 microg kg(-1) h(-1) for 24 h; CA and D7A). We measured renal function and mRNA
      expression, protein level, Serin23 phosphorylation, subcellular distribution, and
      enzyme activity of NKA alpha-1 subunit in the kidney cortex. Diabetes increased
      serum creatinine and urea nitrogen levels (C versus D7), as did ANGII (C versus
      CA, D7 versus D7A). Both diabetes (C versus D7) and ANGII increased NKA alpha-1
      protein level and enzyme activity (C versus CA, D7 versus D7A). Furthermore, the
      combination led to an additive increase (D7 versus D7A, CA versus D7A). NKA alpha
      1 Ser23 phosphorylation was higher both in D7 and ANGII-treated rats in the non
      cytoskeletal fraction, while no signal was detected in the cytoskeletal fraction.
      Control kidneys showed NKA alpha-1 immunopositivity on the basolateral membrane
      of proximal tubular cells, while both D7 and ANGII broadened NKA immunopositivity
      towards the cytoplasm. Our study demonstrates that diabetes mellitus (DM)
      increases the mRNA expression, protein level, Ser23 phosphorylation and enzyme
      activity of renal NKA, which is further elevated by ANGII. Despite an increase in
      total NKA quantity in diabetic nephropathy, the redistribution to the cystosol
      suggests the Na(+) pump is no longer functional. ANGII also caused translocation
      from the basolateral membrane, thus in diabetic states where ANGII level is
      acutely elevated, the loss of NKA will be exacerbated. This provides another
      mechanism by which ANGII blockade is likely to be protective.

PMID- 18818246
TI  - Endothelium-dependent contractions: when a good guy turns bad!
AB  - Endothelial cells can induce contractions of the underlying vascular smooth
      muscle by generating vasoconstrictor prostanoids (endothelium-dependent
      contracting factor; EDCF). The endothelial COX-1 isoform of cyclooxygenase
      appears to play the dominant role in the phenomenon. Its activation requires an
      increase in intracellular Ca(2+) concentration. The production of EDCF is
      inhibited acutely and chronically by nitric oxide (NO), and possibly by
      endothelium-dependent hyperpolarizing factor (EDHF). The main prostanoids
      involved in endothelium-dependent contractions appear to be endoperoxides
      (PGH(2)) and prostacyclin, which activate thromboxane-prostanoid (TP) receptors
      of the vascular smooth muscle cells. Oxygen-derived free radicals can facilitate
      the production and/or the action of EDCF. Endothelium-dependent contractions are
      exacerbated by ageing, obesity, hypertension and diabetes, and thus are likely to
      contribute to the endothelial dysfunction observed in older people and in
      essential hypertensive patients.

PMID- 18818247
TI  - Sympathetic-induced changes in discharge rate and spike-triggered average twitch
      torque of low-threshold motor units in humans.
AB  - Animal and in vitro studies have shown that the sympathetic nervous system
      modulates the contractility of skeletal muscle fibres, which may require
      adjustments in the motor drive to the muscle in voluntary contractions. In this
      study, these mechanisms were investigated in the tibialis anterior muscle of
      humans during sympathetic activation induced by the cold pressor test (CPT; left
      hand immersed in water at 4 degrees C). In the first experiment, 11 healthy men
      performed 20 s isometric contractions at 10% of the maximal torque, before,
      during and after the CPT. In the second experiment, 12 healthy men activated a
      target motor unit at the minimum stable discharge rate for 5 min in the same
      conditions as in experiment 1. Intramuscular electromyographic (EMG) signals and
      torque were recorded and used to assess the motor unit discharge characteristics
      (experiment 1) and spike-triggered average twitch torque (experiment 2). CPT
      increased the diastolic blood pressure and heart rate by (mean +/- S.D.) 18 +/- 9
      mmHg and 4.7 +/- 6.5 beats min(-1) (P < 0.01), respectively. In experiment 1,
      motor unit discharge rate increased from 10.4 +/- 1.0 pulses s(-1) before to 11.1
      +/- 1.4 pulses s(-1) (P < 0.05) during the CPT. In experiment 2, the twitch half
      relaxation time decreased by 15.8 +/- 9.3% (P < 0.05) during the CPT with respect
      to baseline. These results provide the first evidence of an adrenergic modulation
      of contractility of muscle fibres in individual motor units in humans, under
      physiological sympathetic activation.

PMID- 18818248
TI  - Cellular mechanism of the voltage-dependent change in slow potentials generated
      in circular smooth muscle of the guinea-pig gastric corpus.
AB  - The cellular mechanism of the voltage-dependent properties of slow potentials
      were investigated in single bundles of circular smooth muscle isolated from the
      gastric corpus of guinea-pig using conventional microelectrode recordings.
      Hyperpolarization of the membrane by current injection decreased the frequency
      and increased the amplitude of slow potentials linearly. At potentials negative
      of -80 mV, slow potential generation was abolished and a periodic generation of
      clustered unitary potentials was evident. Application of cyclopiazonic acid (CPA,
      20 microM) or thapsigargin (1 microM; inhibitors of Ca(2+)-ATPase), carbonyl
      cyanide m-chlorophenyl hydrazone (CCCP, 0.1 microM; mitochondrial protonophore)
      or 2-aminoethoxydiphenyl borate (2-APB, 20 microM; inhibitor of IP(3) receptor
      mediated Ca(2+) release) depolarized the membrane and reduced or inhibited the
      amplitude and frequency of slow potentials: repolarization of the membrane to the
      resting level by current injection resulted in a recovery of the amplitude of
      slow potentials in the presence of CPA or CCCP, but not 2-APB. The slow
      potentials abolished by thapsigargin did not recover upon membrane
      repolarization. The altered frequency of slow potentials by 2-APB, CPA or CCCP
      was not reversed by membrane repolarization to control potentials. Depolarization
      of the membrane by about 10 mV with high-potassium solution also reduced the
      amplitude and increased the frequency of slow potentials in a manner restored by
      repolarization to control potentials upon current injection, suggesting that
      membrane depolarization did not affect the voltage dependency of pacemaker
      activity. The results indicate that in corpus circular muscles the voltage
      dependency of the frequency and amplitude of slow potentials requires a
      functional Ca(2+) store and mitochondria.

PMID- 18818249
TI  - Co-expression of IGF-1 family members with myogenic regulatory factors following
      acute damaging muscle-lengthening contractions in humans.
AB  - Muscle regeneration following injury is dependent on the ability of muscle
      satellite cells to activate, proliferate and fuse with damaged fibres. This
      process is controlled by the myogenic regulatory factors (MRF). Little is known
      about the temporal relation of the MRF with the expression of known myogenic
      growth factors (i.e. IGF-1) in humans following muscle damage. Eight subjects
      (20.6 +/- 2.1 years; 81.4 +/- 9.8 kg) performed 300 lengthening contractions (180
      deg s(-1)) of their knee extensors in one leg on a dynamometer. Blood and muscle
      samples were collected before and at 4 (T4), 24 (T24), 72 (T72) and 120 h (T120)
      post-exercise. Mechano growth factor (MGF), IGF-1Ea and IGF-1Eb mRNA were
      quantified. Serum IGF-1 did not change over the post-exercise time course. IGF
      1Ea and IGF-1Eb mRNA increased approximately 4- to 6-fold by T72 (P < 0.01) and
      MGF mRNA expression peaked at T24 (P = 0.005). MyoD mRNA expression increased
      approximately 2-fold at T4 (P < 0.05). Myf5 expression peaked at T24 (P < 0.05),
      while MRF4 and myogenin mRNA expression peaked at T72 (P < 0.05). Myf5 expression
      strongly correlated with the increase in MGF mRNA (r(2) = 0.83; P = 0.03), while
      MRF4 was correlated with both IGF-1Ea and -Eb (r(2) = 0.90; r(2) = 0.81,
      respectively; P < 0.05). Immunofluorescence analysis showed IGF-1 protein
      expression localized to satellite cells at T24, and to satellite cells and the
      myofibre at T72 and T120; IGF-1 was not detected at T0 or T4. These results
      suggest that the temporal response of MGF is probably related to the
      activation/proliferation phase of the myogenic programme as marked by an increase
      in both Myf5 and MyoD, while IGF-1Ea and -Eb may be temporally related to
      differentiation as marked by an increase in MRF4 and myogenin expression
      following acute muscle damage.

PMID- 18818250
TI  - Should there be a ceiling on what percentage of GDP countries spend on health?
      No.

PMID- 18818251
TI  - Should there be a ceiling on what percentage of GDP countries spend on health?
      Yes.

PMID- 18818252
TI  - Continuous glucose monitoring in women with diabetes during pregnancy.

PMID- 18818253
TI  - Enabling women to breast feed.

PMID- 18818254
TI  - Effectiveness of continuous glucose monitoring in pregnant women with diabetes:
      randomised clinical trial.
AB  - OBJECTIVE: To evaluate the effectiveness of continuous glucose monitoring during
      pregnancy on maternal glycaemic control, infant birth weight, and risk of
      macrosomia in women with type 1 and type 2 diabetes. DESIGN: Prospective, open
      label randomised controlled trial. SETTING: Two secondary care multidisciplinary
      obstetric clinics for diabetes in the United Kingdom. PARTICIPANTS: 71 women with
      type 1 diabetes (n=46) or type 2 diabetes (n=25) allocated to antenatal care plus
      continuous glucose monitoring (n=38) or to standard antenatal care (n=33).
      INTERVENTION: Continuous glucose monitoring was used as an educational tool to
      inform shared decision making and future therapeutic changes at intervals of 4-6
      weeks during pregnancy. All other aspects of antenatal care were equal between
      the groups. MAIN OUTCOME MEASURES: The primary outcome was maternal glycaemic
      control during the second and third trimesters from measurements of HbA(1c)
      levels every four weeks. Secondary outcomes were birth weight and risk of
      macrosomia using birthweight standard deviation scores and customised birthweight
      centiles. Statistical analyses were done on an intention to treat basis. RESULTS:
      Women randomised to continuous glucose monitoring had lower mean HbA(1c) levels
      from 32 to 36 weeks' gestation compared with women randomised to standard
      antenatal care: 5.8% (SD 0.6) v 6.4% (SD 0.7). Compared with infants of mothers
      in the control arm those of mothers in the intervention arm had decreased mean
      birthweight standard deviation scores (0.9 v 1.6; effect size 0.7 SD, 95%
      confidence interval 0.0 to 1.3), decreased median customised birthweight centiles
      (69% v 93%), and a reduced risk of macrosomia (odds ratio 0.36, 95% confidence
      interval 0.13 to 0.98). CONCLUSION: Continuous glucose monitoring during
      pregnancy is associated with improved glycaemic control in the third trimester,
      lower birth weight, and reduced risk of macrosomia. TRIAL REGISTRATION: Current
      Controlled Trials ISRCTN84461581.

PMID- 18818255
TI  - Commentary: The technology of continuous glucose monitoring.

PMID- 18818256
TI  - A third of pharmacies give poor advice, survey finds.

PMID- 18818257
TI  - Raised blood glucose concentration.

PMID- 18818258
TI  - Dying from dementia--a patient's journey.

PMID- 18818259
TI  - EU updates its plan to reduce drug misuse.

PMID- 18818263
TI  - Nutritional assessment: its role in the provision of nutritional support.
AB  - Generalised undernutrition is common in hospital patients and in the community.
      It is frequently unrecognised and is associated with a range of adverse
      consequences that contribute to increased morbidity and mortality. The National
      Institute for Health and Clinical Excellence recommends that all individuals
      engaging with healthcare or admitted to residential homes in the community should
      be screened for undernutrition. Laboratory investigations have little place in
      the diagnosis of undernutrition: this is primarily a clinical process. In
      particular, the measurement of serum albumin concentration, though widely
      promulgated in the past as an index of nutritional status, is worthless for this
      purpose. Laboratory investigations are, however, of importance: to diagnose
      specific nutritional deficiencies (eg, of trace elements) and to monitor the
      provision of nutritional support, to detect metabolic complications and to assess
      its adequacy (for which the measurement of serum prealbumin concentrations,
      particularly in conjunction with measurements of C-reactive protein, may be of
      value).

PMID- 18818262
TI  - Receiver-operating characteristic curve analysis in diagnostic, prognostic and
      predictive biomarker research.

PMID- 18818264
TI  - Morphological quality and nucleic acid preservation in cytopathology.
AB  - BACKGROUND: Fixation is a chemical or physical procedure to prevent the
      degradation of proteins and tissue morphology. To optimise molecular analysis of
      archival tissues, it is essential that fixation preserves morphology along with
      protein epitopes and DNA/RNA integrity. METHODS: A new formalin-free alcoholic
      based fixative, FineFIX, was used to fix 15 serous effusions and 38 fine-needle
      aspirates, and cellular morphology and nucleic acid quality were evaluated.
      RESULTS: The cytomorphology of the effusions and fine-needle aspirates obtained
      with FineFIX fixation was similar to that obtained with formalin-fixed
      counterparts. Immunocytochemistry showed comparable results with the traditional
      fixative, but FineFIX preserved higher-molecular-mass DNA and RNA, as
      demonstrated by successful PCR of large amplification products of >2000 bp.
      CONCLUSIONS: The formalin-free fixative produced not only satisfactory results
      for immunocytochemistry on cytological smears and cell blocks, but also excellent
      preservation of DNA and RNA, which can also be efficiently used for sophisticated
      molecular techniques.

PMID- 18818265
TI  - Human herpes virus 6 in archival cardiac tissues from children with idiopathic
      dilated cardiomyopathy or congenital heart disease.
AB  - OBJECTIVE: To explore the possible role of human herpes virus 6 (HHV-6) in
      cardiac disorders in childhood in a retrospective study on archival specimens of
      explanted hearts. METHODS: 16 children (median age at transplantation 11.0 years)
      with idiopathic dilated cardiomyopathy (DCM) and 19 children (median age at
      transplantation 1.0 year) with congenital heart disease (CHD), previously found
      to be negative for other cardiotropic viruses such as enteroviruses, adenovirus,
      parvovirus B19, cytomegalovirus and Epstein-Barr virus, were tested for HHV-6 by
      quantitative real-time PCR and by genotyping. In addition, HHV-7/8 infection was
      investigated by qualitative PCR. RESULTS: HHV-6 B variant was detected in 11 of
      35 samples (31.4%) with a mean viral load of 3.1 x 102 copies/microg of DNA. When
      assessed by heart disorder, the prevalence was different in the two groups (43.7%
      in DCM and 21% in CHD) while the mean viral loads were similar. In a logistic
      multivariate analysis HHV-6 was independently associated with DCM, taking CHD as
      reference and adjusting for age (best estimate: OR = 6.94; 95% CI 1.00 to 49.85;
      p = 0.05). CONCLUSIONS: Although the clinical significance of the results is
      unknown, HHV-6 B genome is frequently detected in explanted hearts from children
      with DCM and to a lesser extent with CHD, thus adding evidence for HHV-6 cardiac
      involvement.

PMID- 18818266
TI  - Overexpression of von Hippel-Lindau protein in skeletal muscles of patients with
      chronic obstructive pulmonary disease.
AB  - BACKGROUND: A significant number of patients with chronic obstructive pulmonary
      disease (COPD) exhibit skeletal muscle wasting and decreased capillary area
      formation, which correlate with increased mortality. AIM: To determine the
      molecular mechanisms mediating decreased capillary formation in COPD. METHODS: 24
      patients with COPD and 12 matching controls were recruited. Patients with COPD
      were classified into mild, moderate and severe groups according to GOLD (global
      initiative for chronic obstructive lung disease) criteria. Biopsy specimens were
      obtained from the tibialis anterior muscle. Fibre typing and capillary formation,
      together with messenger RNA (mRNA) expression of hypoxia-inducible factors
      (HIF1alpha and HIF3alpha), vascular endothelial growth factors (VEGF-A, VEGF-B
      and VEGF-C isoforms) and von Hippel-Lindau (VHL) protein, were determined. VHL
      expression and localisation were further studied by immunohistochemistry.
      RESULTS: Skeletal muscle capillary formation decreased significantly with
      increasing disease severity. Compared with controls, a tendency to mRNA
      overexpression of HIF1alpha, HIF3alpha and VEGF isoforms was observed in mild and
      moderate COPD, which decreased at the severe stage. In contrast, skeletal muscle
      biopsy samples from patients with COPD exhibited significant overexpression of
      VHL at both the mRNA and protein level by immunohistochemistry. VHL protein was
      further determined to be localised to satellite cells. CONCLUSIONS:
      Overexpression of VHL was identified in the skeletal muscle of patients with
      COPD. Increased VHL activity may have a negative effect on transduction of the
      hypoxic signal and may contribute to decreased capillarisation in skeletal
      muscles of patients with COPD.

PMID- 18818267
TI  - The gross appearances of fine needle aspiration cytology samples.
AB  - AIMS: This study set out to photograph and describe the gross appearances of fine
      needle aspiration (FNA) cytology samples of commonly encountered lesions.
      METHODS: During a 2 year period, a cytopathologist photographed the gross
      appearances of near patient FNA samples, concentrating on commonly encountered
      lesions. RESULTS: The gross appearances are described, accompanied by
      photographic illustrations. CONCLUSIONS: This paper describes and illustrates the
      gross appearances of FNA cytology samples of some commonly encountered lesions.

PMID- 18818268
TI  - A case of Erysipelothrix rhusiopathiae causing bilateral endogenous
      endophthalmitis.
AB  - This report describes a case of bilateral endogenous endophthalmitis caused by
      Erysipelothrix rhusiopathiae, an occupational zoonotic pathogen, which was
      successfully treated with intravenous penicillin G followed by oral linezolid.
      This is believed to be the first report of E rhusiopathiae causing endogenous
      endophthalmitis.

PMID- 18818269
TI  - Early introduction of fish decreases the risk of eczema in infants.
AB  - BACKGROUND: Atopic eczema in infants has increased in western societies.
      Environmental factors and the introduction of food may affect the risk of eczema.
      AIMS: To investigate the prevalence of eczema among infants in western Sweden,
      describe patterns of food introduction and assess risk factors for eczema at 1
      year of age. METHODS: Data were obtained from a prospective, longitudinal cohort
      study of infants born in western Sweden in 2003; 8176 families were randomly
      selected and, 6 months after the infant's birth, were invited to participate and
      received questionnaires. A second questionnaire was sent out when the infants
      were 12 months old. Both questionnaires were completed and medical birth register
      data were obtained for 4921 infants (60.2% of the selected population). RESULTS:
      At 1 year of age, 20.9% of the infants had previous or current eczema. Median age
      at onset was 4 months. In multivariable analysis, familial occurrence of eczema,
      especially in siblings (OR 1.87; 95% confidence interval (CI) 1.50 to 2.33) or
      the mother (OR 1.54; 95% CI 1.30 to 1.84), remained an independent risk factor.
      Introducing fish before 9 months of age (OR 0.76; 95% CI 0.62 to 0.94) and having
      a bird in the home (OR 0.35; 95% CI 0.17 to 0.75) were beneficial. CONCLUSIONS:
      One in five infants suffer from eczema during the first year of life. Familial
      eczema increased the risk, while early fish introduction and bird keeping
      decreased it. Breast feeding and time of milk and egg introduction did not affect
      the risk.

PMID- 18818270
TI  - Correlation of patient maximum skin doses in cardiac procedures with various dose
      indicators.
AB  - In most countries of European Union, legislation requires the determination of
      the total skin dose received by patients during interventional procedures in
      order to prevent deterministic damages. Various dose indicators like dose-area
      product (DAP), cumulative dose (CD) and entrance dose at the patient plane (EFD)
      are used for patient dosimetry purposes in clinical practice. This study aimed at
      relating those dose indicators with doses ascribed to the most irradiated areas
      of the patient skin usually expressed in terms of local maximal skin dose (MSD).
      The study was performed in two different facilities for two most common cardiac
      procedures coronary angiography (CA) and percutaneous coronary interventions
      (PCI). For CA procedures, the registered values of fluoroscopy time, total DAP
      and MSD were in the range (0.7-27.3) min, (16-317) Gy cm(2) and (43-1507) mGy,
      respectively, and for interventions, accordingly (2.1-43.6) min, (17-425) Gy
      cm(2), (71-1555) mGy. Moreover, for CA procedures, CD and EFD were in the ranges
      (295-4689) mGy and (121-1768) mGy and for PCI (267-6524) mGy and (68-2279) mGy,
      respectively. No general and satisfactory correlation was found for safe
      estimation of MSD. However, results show that the best dose indicator which might
      serve for rough, preliminary estimation is DAP value. In the study, the
      appropriate trigger levels were proposed for both facilities.

PMID- 18818271
TI  - Gene expression and secretion of LH and FSH in relation to gene expression of
      GnRH receptors in the brushtail possum (Trichosurus vulpecula) demonstrates
      highly conserved mechanisms.
AB  - In eutherian mammals, the gonadotrophins (LH and FSH) are synthesized and stored
      in gonadotroph cells under the regulation of multiple mechanisms including GnRH.
      Very little is known about the regulation of gonadotrophin secretion and storage
      in pituitary glands of marsupials. This study revealed, using quantitative PCR
      and heterologous RIA techniques, that LHB mRNA expression levels remained
      constant over the oestrous cycle, regardless of the presence of a preovulatory LH
      surge, which is characteristic of a hormone secreted under regulation. Our
      sampling regime was unable to detect pulses of LH during the follicular phase,
      although GNRHR mRNA levels had increased at this time. Pulses of LH were,
      however, detected in the luteal phase of cycling females, in anoestrus females
      and in males. There was a positive correlation between gene expression of FSHB
      and plasma levels of FSH at different stages of the oestrous cycle and no pulses
      of FSH were detected at any time; all characteristics of a hormone secreted via
      the constitutive pathway. Using in situ hybridisation and immunohistochemistry
      methods, we determined that mRNA expression of LHB and FSHB, and protein storage
      of gonadotrophins exhibited a similar pattern of localisation within the
      pituitary gland. Additionally, sexual dimorphism of gonadotroph populations was
      evident. In summary, these findings are similar to that reported in eutherians
      and considering that marsupial evolution diverged from eutherians over 100
      million years ago suggests that the regulation of gonadotrophins is highly
      conserved indeed.

PMID- 18818273
TI  - Understanding sustained behavior change: the role of life crises and the process
      of reinvention.
AB  - Much research has addressed behavior change but has tended to focus on short term
      changes. This study aimed to explore the mechanisms behind sustained changes in
      behavior and involved qualitative interviews with 34 ;success stories' who had
      either lost weight through changes in diet and exercise (n = 24) or stopped
      smoking (n = 10) and had maintained this change for at least 3 years. The results
      showed that the majority described how their sustained behavior change had been
      triggered by a significant life crisis relating to their health, relationships or
      salient milestones. This initial change was then translated into sustained change
      if three sustaining conditions were met: the function of the unhealthy behavior
      was disrupted, the individual perceived that their choice over carrying out the
      unhealthy behavior had been reduced and they adhered to a behavioral model of
      their problem. Further, these conditions functioned by enabling a process of
      reinvention with participants showing a shift in identity toward a new healthier
      self. The results are discussed in terms of self-regulation and the establishment
      of a new post-crisis healthier equilibrium.

PMID- 18818272
TI  - Increasing 3alpha,5alpha-THP following inhibition of neurosteroid biosynthesis in
      the ventral tegmental area reinstates anti-anxiety, social, and sexual behavior
      of naturally receptive rats.
AB  - The progesterone metabolite and neurosteroid, 5alpha-pregnan-3alpha-ol-20-one
      (3alpha,5alpha-THP), has actions in the midbrain ventral tegmental area (VTA) to
      modulate lordosis, but its effects on other reproductively relevant behaviors are
      not well understood. Effects on exploration, anxiety, and social behavior
      resulting from inhibition of 3alpha,5alpha-THP formation, as well as
      3alpha,5alpha-THP enhancement, were investigated in the midbrain VTA. Naturally
      sexually receptive, female rats (n=8-10/group) received infusions aimed at the
      midbrain VTA of vehicle, PK11195 (an inhibitor of neurosteroidogenesis), and/or
      indomethacin (an inhibitor of 3alpha,5alpha-THP formation from prohormones), and
      were subsequently infused with vehicle or FGIN 1-27 (a neurosteroidogenesis
      enhancer). The rats were then assessed in a behavioral battery that examined
      exploration (open field), anxiety (elevated plus maze), social (social
      interaction), and sexual (paced mating) behavior. Inhibition of 3alpha,5alpha-THP
      formation decreased exploratory, anti-anxiety, social, and sexual behavior, as
      well as midbrain 3alpha,5alpha-THP levels. Infusions of FGIN 1-27 following
      3alpha,5alpha-THP inhibition restored these behaviors and midbrain 3alpha,5alpha
      THP levels to those commensurate with control rats that had not been administered
      inhibitors. These findings suggest that 3alpha,5alpha-THP formation in the
      midbrain VTA may influence appetitive, as well as consummatory, aspects of mating
      behavior.

PMID- 18818274
TI  - Resilience and depression: perspectives from primary care.
AB  - Resilience refers to the capacity for successful adaptation or change in the face
      of adversity. This concept has rarely been applied to the study of distress and
      depression. We propose two key elements of resilience - ordinary magic and
      personal medicine - which enable people to survive and flourish despite current
      experience of emotional distress. We investigate the extent to which these
      elements are considered important by a sample of 100 people, drawn from a
      longitudinal study of the management of depression in primary care in Victoria,
      Australia. We also assess how respondents rate personal resilience in comparison
      with help received from professional sources. Our data are obtained from semi
      structured telephone interviews, and analysed inductively through refinement of
      our theoretical framework. We find substantial evidence of resilience both in
      terms of ordinary magic - drawing on existing social support and affectional
      bonds; and in terms of personal medicine - building on personal strengths and
      expanding positive emotions. There is a strong preference for personal over
      professional approaches to dealing with mental health problems. We conclude that
      personal resilience is important in the minds of our respondents, and that these
      elements should be actively considered in future research involving people with
      experience of mental health problems.

PMID- 18818275
TI  - Negotiating the diagnostic uncertainty of contested illnesses: physician
      practices and paradigms.
AB  - In the absence of scientific consensus about contested illnesses such as Chronic
      Fatigue Syndrome (CFS), Multiple Chemical Sensitivities (MCS), and Gulf War
      Syndrome (GWS), physicians must make sense of competing accounts and develop
      practices for patient evaluation. A survey of 800 United States physicians
      examined physician propensity to diagnose CFS, MCS, and GWS, and the factors
      shaping clinical decision making. Results indicate that a substantial portion of
      physicians, including nonexperts, are diagnosing CFS, MCS, and GWS. Diagnosing
      physicians manage the uncertainty associated with these illnesses by using
      strategies that enhance bounded rationality and aid in thinking beyond current
      disease models. Strategies include consulting ancillary information sources,
      conducting analytically informed testing, and considering physiological
      explanations of causation. By relying on these practices and paradigms,
      physicians fit CFS, MCS, and GWS into an explanatory system that makes them
      credible and understandable to them, their patients, and the medical community.
      Findings suggest that physicians employ rational decision making for diagnosing
      contested illnesses, creating a blueprint of how illnesses lacking conclusive
      pathogenic and etiological explanations can be diagnosed. Findings also suggest
      that patients with contested illnesses might benefit from working with physicians
      who use these diagnostic strategies, since they help manage the complexity and
      ambiguity of the contested illness diagnostic process and aid in diagnosis. In
      addition, findings provide a window into how emerging illnesses get diagnosed in
      the absence of medical and scientific consensus, and suggest that diagnosing
      physicians advance the legitimacy of controversial illnesses by constructing the
      means for their diagnosis.

PMID- 18818276
TI  - Discourse of 'transformational leadership' in infection control.
AB  - The article explores the impact of the ;transformational leadership' style in the
      role of modern matron with regards to infection control practices. Policy and
      guidance on the modern matron role suggest that it is distinctive in its
      combination of management and clinical components, and in its reliance on
      transformational leadership. Senior nurses are therefore expected to motivate
      staff by creating high expectations, modelling appropriate behaviour, and
      providing personal attention to followers by giving respect and responsibility.
      In this article, we draw on policy documents and interview data to explore the
      potential impact of this new management style on infection control practices.
      Combining the techniques of discourse analysis and corpus linguistics, we
      identify examples where matrons appear to disassociate themselves from the role
      of ;an empowered manager' who has control over human and financial resources to
      resolve problems in infection control efficiently.

PMID- 18818277
TI  - The artist as surgical ethnographer: participant observers outside the social
      sciences.
AB  - Artists and novelists have rarely been considered as ethnographers in the medical
      social sciences. This article pursues the idea that ethnographically informed
      artistic works can be viewed as critical cultural texts alongside sociological
      and anthropological studies of surgery. It is proposed that art provides fresh
      perspectives on topics of interest in health sociology and medical anthropology
      while simultaneously expanding our engagement with ethnographic representation.
      Discussion revolves around a video installation incorporating images of heart
      surgery by contemporary artist Bill Viola and a recent novel by Ian McEwan
      detailing the day-in-the-life of a neurosurgeon. Considering an emerging re
      engagement, particularly in contemporary art that artists are having with medical
      themes, and a concurrent ;ethnographic turn' in art practice, it seems timely to
      recognize the potentially critical contribution of non-social scientist
      ethnographers to our understanding of a rapidly changing medical culture.

PMID- 18818278
TI  - Constructions of the self in interaction with the Beck Depression Inventory.
AB  - In this article, I am interested in discourses of people completing the Polish
      version of the Beck Depression Inventory (BDI). I focus upon the negotiation of
      the spaces for constructing the self opened by the BDI. My corpus consists of
      transcripts of 50 sessions in which self-reportedly healthy people were asked to
      ;think aloud' while completing the BDI. I shall demonstrate that in interactions
      with the ;depression scale', the informants mostly rejected the spaces offered by
      it. Three strategies of such rejection are discussed: reformulation,
      recontextualization and an explicit challenge to the categories offered by the
      BDI. I shall argue that the concerns of lived experience in a particular context,
      when not subdued by the relationship of power in the situation of medical
      examination, overrule the frame imposed by the a-contextual questionnaire of
      sadness. Insight into depression or its intensity offered by ;context-free'
      psychological or psychiatric instrument, set outside lived experience, is
      extremely problematic.

PMID- 18818279
TI  - Hemodynamics in a lethal basilar artery aneurysm just before its rupture.
AB  - BACKGROUND AND PURPOSE: Hemodynamics is thought to play an important role in the
      mechanisms of cerebral aneurysm initiation, progression, and rupture. The purpose
      of this study was to present a hemodynamic study of a cerebral aneurysm
      immediately before its rupture to assess whether previously identified
      hemodynamic characteristics would classify this aneurysm in the high-risk
      category. MATERIALS AND METHODS: A patient-specific computational fluid dynamics
      model was constructed from 3D rotational angiographic images acquired just hours
      before the aneurysm had ruptured. A pulsatile flow simulation was carried out,
      and the hemodynamics characterized by the concentration of the inflow jet, the
      size of the flow impingement region, and the complexity and stability of the flow
      pattern. RESULTS: We found that the aneurysm had a concentrated inflow jet that
      impacted onto a small region of the dome of the aneurysm and created a complex,
      unstable flow pattern. CONCLUSIONS: This study supports the proposition that
      hemodynamic characteristics derived from image-based computational models can be
      used to identify cerebral aneurysms at high risk for rupture.

PMID- 18818280
TI  - Susceptibility-weighted imaging in cranial dural arteriovenous fistulas.

PMID- 18818281
TI  - Gene expression profile for ectopic versus eutopic endometrium provides new
      insights into endometriosis oncogenic potential.
AB  - Endometriosis is a common gynecological disorder characterized by pain and
      infertility, where the lesions disseminate everywhere in the body with a
      preference for the pelvis. In that, it could be regarded as a benign metastatic
      disease, because its issue is not fatal. However, the molecular bases of this
      intriguing clinical condition are not well known. The objective of this study is
      to characterize the transcriptome differences between eutopic vs. ectopic
      endometrium with a special interest in pathways involved in cancerogenesis. We
      performed two hybridizations in technical replicate on highly specific long
      oligonucleotides microarrays (NimbleGen), with cDNA prepared from six-patients
      pools, where the same patient provided both eutopic and ectopic endometrium
      (endometriomas). To confirm the expression microarrays data, quantitative RT-PCR
      validation was performed on 12 individuals for 20 genes. Over 8000 transcripts
      were significantly modified (more than twice) in the lesions corresponding to
      5600 down- or up-regulated genes. These were clustered through DAVID
      Bioinformatics Resources into 55 functional groups. The data are presented in a
      detailed and visual way on 24 Kyoto Encyclopedia of Genes and Genomes (KEGG)
      pathways implemented with induction ratios for each differentially expressed
      gene. An outstanding control of the cell cycle and a very specific modulation of
      the HOX genes were observed and provide some new evidence on why endometriosis
      only very rarely degenerates into cancer. The study constitutes a noteworthy
      update of gene profiling in endometriosis, by delivering the most complete and
      reliable list of dysregulated genes to date.

PMID- 18818282
TI  - Cocaine- and amphetamine-regulated transcript accelerates termination of follicle
      stimulating hormone-induced extracellularly regulated kinase 1/2 and Akt
      activation by regulating the expression and degradation of specific mitogen
      activated protein kinase phosphatases in bovine granulosa cells.
AB  - Pleiotropic actions of cocaine- and amphetamine-regulated transcript (CART) are
      well described in the central nervous system and periphery, but the intracellular
      mechanisms mediating biological actions of CART are poorly understood. Although
      CART is not expressed in mouse ovaries, we have previously established CART as a
      novel intracellular regulator of estradiol production in bovine granulosa cells.
      We demonstrated that inhibitory actions of CART on estradiol production are
      mediated through inhibition of FSH-induced cAMP accumulation, Ca(2+) influx, and
      aromatase mRNA expression via a G(o/i)-dependent pathway. We also reported that
      FSH-induced estradiol production is dependent on Erk1/2 and Akt signaling, and
      CART may regulate other signaling proteins downstream of cAMP essential for
      estradiol production. Here, we demonstrate that CART is a potent inhibitor of FSH
      stimulated Erk1/2 and Akt signaling and the mechanisms involved. Transient CART
      stimulation of bovine granulosa cells shortens the duration of FSH-induced Erk1/2
      and Akt signaling whereas a prolonged (24 h) CART treatment blocks Erk1/2 and Akt
      activation in response to FSH. This CART-induced accelerated termination of
      Erk1/2 and Akt signaling is mediated both by induced expression and impaired
      ubiquitin-mediated proteasome degradation of dual specific phosphatase 5 (DUSP5)
      and protein phosphatase 2A. Results also support existence of a negative feedback
      loop in which CART via a G(o/i)-MAPK kinase dependent pathway activates Erk1/2,
      and the latter induces DUSP5 expression. Moreover, small interfering RNA mediated
      ablation of DUSP5 and/or protein phosphatase 2A prevents the CART-induced early
      termination of Erk1/2 and Akt signaling. Results provide novel insight into the
      intracellular mechanism of action of CART in regulation of FSH-induced MAPK
      signaling.

PMID- 18818283
TI  - Unique ERalpha cistromes control cell type-specific gene regulation.
AB  - Estrogens play an important role in normal physiology and in a variety of
      pathological states involving diverse tissues including breast and bone. The
      mechanism by which estrogens exert cell type- and disease-specific effects,
      however, remains to be explained. We have compared the gene expression profile of
      the MCF7 breast cancer cell line with that of the osteoblast-like cell line U2OS
      ERalpha by expression microarrays. We find that fewer than 10% of the 17beta
      estradiol (E2)-regulated genes are common to both cell types. We have validated
      this in primary calvarial osteoblasts. To dissect the mechanism underlying the
      cell type-specific E2 regulation of gene expression in MCF7 and U2OS-ERalpha
      cells, we compared the ERalpha binding sites on DNA in the two cell types by
      performing chromatin immunoprecipitation (ChIP) on genomic tiling arrays (ChIP-on
      chip). Consistent with the distinct patterns of E2-regulated gene expression in
      these two cell lines, we find that the vast majority of ERalpha binding sites are
      also cell type specific and correlate both in position and number with cell type
      specific gene regulation. Interestingly, although the forkhead factor FoxA1 plays
      a critical role in defining the ERalpha cistrome in MCF7 cells, it is not
      expressed in U2OS-ERalpha cells, and forkhead motifs are not enriched in the
      ERalpha cistrome in these cells. Finally, the ERalpha cistromes are correlated
      with cell type-specific epigenetic histone modifications. These results support a
      model for the cell type-specific action of E2 being driven primarily through
      specific ERalpha occupancy of epigenetically marked cis-regulatory regions of
      target genes.

PMID- 18818284
TI  - Role of adenosine 5'-monophosphate-activated protein kinase in interleukin-6
      release from isolated mouse skeletal muscle.
AB  - IL-6 is released from skeletal muscle during exercise and has consequently been
      implicated to mediate beneficial effects on whole-body metabolism. Using 5
      aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside (AICAR), a pharmacological
      activator of 5'-AMP-activated protein kinase (AMPK), we tested the hypothesis
      that AMPK modulates IL-6 release from isolated muscle. Skeletal muscle from
      AMPKalpha2 kinase-dead transgenic, AMPKalpha1 knockout (KO) and AMPKgamma3 KO
      mice and respective wild-type littermates was incubated in vitro, in the absence
      or presence of 2 mmol/liter AICAR. Skeletal muscle from wild-type mice was also
      incubated with the AMPK activator A-769662. Incubation of mouse glycolytic
      extensor digitorum longus and oxidative soleus muscle for 2 h was associated with
      profound IL-6 mRNA production and protein release, which was suppressed by AICAR
      (P < 0.001). Basal IL-6 release from soleus was increased between AMPKalpha2
      kinase-dead and AMPKalpha1 KO and their respective wild-type littermates (P <
      0.05), suggesting AMPK participates in the regulation of IL-6 release from
      oxidative muscle. The effect of AICAR on muscle IL-6 release was similar between
      AMPKalpha2 KD, AMPKalpha1 KO, and AMPKgamma3 KO mice and their respective wild
      type littermates (P < 0.001), indicating AICAR-mediated suppression of IL-6 mRNA
      expression and protein release is independent of AMPK function. However, IL-6
      release from soleus, but not extensor digitorum longus, was reduced 45% by A
      769662. Our results on basal and A-769662-mediated IL-6 release provide evidence
      for a role of AMPK in the regulation of IL-6 release from oxidative skeletal
      muscle. Furthermore, in addition to activating AMPK, AICAR suppresses IL-6
      release by an unknown, AMPK-independent mechanism.

PMID- 18818285
TI  - Distinct melanocortin 2 receptor accessory protein domains are required for
      melanocortin 2 receptor interaction and promotion of receptor trafficking.
AB  - Melanocortin 2 receptor (MC2R) is the receptor for the pituitary hormone ACTH.
      When activated, MC2R stimulates cAMP production and adrenal steroidogenesis. The
      functional expression of the receptor requires melanocortin 2 receptor accessory
      protein (MRAP), a single-transmembrane domain protein involved in the trafficking
      of MC2R from the endoplasmic reticulum to the cell surface. Mutations in both
      MC2R and MRAP cause the inherited disease familial glucocorticoid deficiency. At
      present, little is known regarding the mechanism of MRAP in MC2R functional
      expression. Here we report the characterization of MRAP in the trafficking of
      MC2R to the cell surface and the formation of a functional receptor. We identify
      the transmembrane domain of MRAP as the MC2R interaction domain and a conserved N
      terminal tyrosine-rich domain of MRAP that is required for trafficking MC2R to
      the cell surface.

PMID- 18818286
TI  - Mouse models of Alzheimer's dementia: current concepts and new trends.
AB  - It is lay knowledge now that Alzheimer's dementia (AD) is one of the most
      devastating diseases afflicting our societies. A major thrust in search for a
      cure has relied in the development of animal models of the disease. Thanks to
      progress in the genetics of the rare inherited forms of AD, various transgenic
      mouse models harboring human mutated proteins were developed, yielding very
      significant advancements in the understanding of pathological pathways. Although
      these models led to testing many different new therapies, none of the preclinical
      successes have translated yet into much needed therapeutic improvements. Further
      insight into the metabolic disturbances that are probably associated with the
      onset of the disease may also rely on new animal models of AD involving
      insulin/IGF-I signaling that could mimic the far most common sporadic forms of AD
      associated with old age. Combination of models of familial AD that develop severe
      amyloidosis with those displaying defects in insulin/IGF-I signaling may help
      clarify the link between putative initial metabolic disturbances and mechanisms
      of pathological progression.

PMID- 18818287
TI  - Developmental and diurnal dynamics of Pax4 expression in the mammalian pineal
      gland: nocturnal down-regulation is mediated by adrenergic-cyclic adenosine 3',5'
      monophosphate signaling.
AB  - Pax4 is a homeobox gene that is known to be involved in embryonic development of
      the endocrine pancreas. In this tissue, Pax4 counters the effects of the related
      protein, Pax6. Pax6 is essential for development of the pineal gland. In this
      study we report that Pax4 is strongly expressed in the pineal gland and retina of
      the rat. Pineal Pax4 transcripts are low in the fetus and increase postnatally;
      Pax6 exhibits an inverse pattern of expression, being more strongly expressed in
      the fetus. In the adult the abundance of Pax4 mRNA exhibits a diurnal rhythm in
      the pineal gland with maximal levels occurring late during the light period.
      Sympathetic denervation of the pineal gland by superior cervical ganglionectomy
      prevents the nocturnal decrease in pineal Pax4 mRNA. At night the pineal gland is
      adrenergically stimulated by release of norepinephrine from the sympathetic
      innervation; here, we found that treatment with adrenergic agonists suppresses
      pineal Pax4 expression in vivo and in vitro. This suppression appears to be
      mediated by cAMP, a second messenger of norepinephrine in the pineal gland, based
      on the observation that treatment with a cAMP mimic reduces pineal Pax4 mRNA
      levels. These findings suggest that the nocturnal decrease in pineal Pax4 mRNA is
      controlled by the sympathetic neural pathway that controls pineal function acting
      via an adrenergic-cAMP mechanism. The daily changes in Pax4 expression may
      influence gene expression in the pineal gland.

PMID- 18818288
TI  - Evidence of diminished glucose stimulation and endoplasmic reticulum function in
      nonoscillatory pancreatic islets.
AB  - Pulsatility is a fundamental feature of pancreatic islets and a hallmark of
      hormone secretion. Isolated pancreatic islets endogenously generate rhythms in
      secretion, metabolic activity, and intracellular calcium ([Ca(2+)](i)) that are
      important to normal physiological function. Few studies have directly compared
      oscillatory and nonoscillatory islets to identify possible differences in
      function. We investigated the hypothesis that the loss of these oscillations is a
      leading indicator of islet dysfunction by comparing oscillatory and
      nonoscillatory mouse islets for multiple parameters of function. Nonoscillatory
      islets displayed elevated basal [Ca(2+)](i) and diminished [Ca(2+)](i) response
      and insulin secretory response to 3-28 mm glucose stimulation compared with
      oscillatory islets, suggesting diminished glucose sensitivity. We investigated
      several possible mechanisms to explain these differences. No differences were
      observed in mitochondrial membrane potential, estimated ATP-sensitive potassium
      channel and L-type calcium channel activity, or cell death rates. Nonoscillatory
      islets, however, showed a reduced response to the sarco(endo)plasmic reticulum
      calcium ATPase inhibitor thapsigargin, suggesting a disruption in calcium
      homeostasis in the endoplasmic reticulum (ER) compared with oscillatory islets.
      The diminished ER calcium homeostasis among nonoscillatory islets was also
      consistent with the higher cytosolic calcium levels observed in 3 mm glucose.
      Inducing mild damage with low-dose proinflammatory cytokines reduced islet
      oscillatory capacity and produced similar effects on glucose-stimulated
      [Ca(2+)](i), basal [Ca(2+)](i), and thapsigargin response observed among
      untreated nonoscillatory islets. Our data suggest the loss of oscillatory
      capacity may be an early indicator of diminished islet glucose sensitivity and ER
      dysfunction, suggesting targets to improve islet assessment.

PMID- 18818289
TI  - Identification and characterization of nesfatin-1 immunoreactivity in endocrine
      cell types of the rat gastric oxyntic mucosa.
AB  - Hypothalamic nesfatin-1, derived from the nucleobindin2 (NUCB2) precursor,
      inhibits nocturnal food intake and body weight gain in rats. Nesfatin-1 is able
      to cross the blood-brain barrier, suggesting a peripheral source of nesfatin-1.
      Many centrally acting food intake regulatory neuropeptides are also produced in
      the periphery, especially in the gastrointestinal tract. Therefore, we
      investigated the gene expression of NUCB2 and distribution of nesfatin-1
      immunoreactive cells in the stomach. Microarray mRNA expression profiles in
      purified small endocrine cells of the gastric mucosa substantiated by
      quantitative RT-PCR showed significantly higher NUCB2 mRNA expression compared
      with brain and heart. Western blot confirmed the expression of NUCB2 protein and
      its transport into a secretory soluble fraction of gastric mucosal endocrine cell
      homogenates. Immunohistochemical colabeling for nesfatin-1 and ghrelin, histidine
      decarboxylase, or somatostatin revealed two subtypes of nesfatin-1-positive
      endocrine cells. Cells in the midportion of the glands coexpressed nesfatin-1 and
      ghrelin, whereas few cells in the glandular base coexpressed nesfatin-1 and
      somatostatin or histidine decarboxylase. High-resolution three-dimensional volume
      imaging revealed two separate populations of intracytoplasmic vesicles in these
      cells, one containing nesfatin-1 and the other ghrelin immunoreactivity.
      Microarray rat genome expression data of NUCB2 in small gastric endocrine cells
      confirmed by quantitative RT-PCR showed significant down-regulation of NUCB2
      after 24 h fasting. In summary, NUCB2 mRNA expression as well as protein content
      is present in a specific subset of gastric endocrine cells, most of which
      coexpress ghrelin. NUCB2 gene expression is significantly regulated by
      nutritional status, suggesting a regulatory role of peripheral nesfatin-1 in
      energy homeostasis.

PMID- 18818291
TI  - A select combination of clinically relevant phytoestrogens enhances estrogen
      receptor beta-binding selectivity and neuroprotective activities in vitro and in
      vivo.
AB  - We have previously shown that a number of naturally occurring phytoestrogens and
      derivatives were effective to induce some measures of neuroprotective responses
      but at a much lower magnitude than those induced by the female gonadal estrogen
      17beta-estradiol. In the present study, we sought to investigate whether a
      combination of select phytoestrogens could enhance neural responses without
      affecting the reproductive system. We performed a range of comparative analyses
      of the estrogen receptor (ER) alpha/beta binding profile, and in vitro to in vivo
      estrogenic activities in neural and uterine tissues induced by clinically
      relevant phytoestrogens: genistein, daidzein, equol, and IBSO03569, when used
      alone or in combination. Our analyses revealed that both the ERalpha/beta binding
      profile and neural activities associated with individual phytoestrogens are
      modifiable when used in combination. Specifically, the combination of genistein
      plus daidzein plus equol resulted in the greatest binding selectivity for ERbeta
      and an overall improved efficacy/safety profile when compared with single or
      other combined formulations, including: 1) an approximate 30% increase in ERbeta
      binding selectivity (83-fold over ERalpha); 2) a greater effect on neuronal
      survival against toxic insults in primary neurons; 3) an enhanced activity in
      promoting neural proactive defense mechanisms against neurodegeneration,
      including mitochondrial function and beta-amyloid degradation; and 4) no effect
      on uterine growth. These observations suggest that select phytoestrogens in
      combination have the therapeutic potential of an alternative approach to
      conventional estrogen therapy for long-term safe use to reduce the increased risk
      of cognitive decline and neurodegenerative disease associated with menopause in
      women.

PMID- 18818290
TI  - Insulin regulates glucagon-like peptide-1 secretion from the enteroendocrine L
      cell.
AB  - Insulin resistance and type 2 diabetes mellitus are associated with impaired
      postprandial secretion of glucagon-like peptide-1 (GLP-1), a potent
      insulinotropic hormone. The direct effects of insulin and insulin resistance on
      the L cell are unknown. We therefore hypothesized that the L cell is responsive
      to insulin and that insulin resistance impairs GLP-1 secretion. The effects of
      insulin and insulin resistance were examined in well-characterized L cell models:
      murine GLUTag, human NCI-H716, and fetal rat intestinal cells. MKR mice, a model
      of chronic hyperinsulinemia, were used to assess the function of the L cell in
      vivo. In all cells, insulin activated the phosphatidylinositol 3 kinase-Akt and
      MAPK kinase (MEK)-ERK1/2 pathways and stimulated GLP-1 secretion by up to 275 +/-
      58%. Insulin resistance was induced by 24 h pretreatment with 10(-7) m insulin,
      causing a marked reduction in activation of Akt and ERK1/2. Furthermore, both
      insulin-induced GLP-1 release and secretion in response to glucose-dependent
      insulinotropic peptide and phorbol-12-myristate-13-acetate were significantly
      attenuated. Whereas inhibition of phosphatidylinositol 3 kinase with LY294002
      potentiated insulin-induced GLP-1 release, secretion was abrogated by inhibiting
      the MEK-ERK1/2 pathway with PD98059 or by overexpression of a kinase-dead MEK1
      ERK2 fusion protein. Compared with controls, MKR mice were insulin resistant and
      displayed significantly higher fasting plasma insulin levels. Furthermore, they
      had significantly higher basal GLP-1 levels but displayed impaired GLP-1
      secretion after an oral glucose challenge. These findings indicate that the
      intestinal L cell is responsive to insulin and that insulin resistance in vitro
      and in vivo is associated with impaired GLP-1 secretion.

PMID- 18818292
TI  - Induction of heparanase in bovine granulosa cells by luteinizing hormone:
      possible role during the ovulatory process.
AB  - Follicular development, follicular rupture, and corpus luteum (CL) formation are
      accompanied by extensive tissue remodeling. We examined whether heparanase
      (HPSE), which cleaves heparan sulfate glycosaminoglycans, is induced during these
      processes. Prostaglandin F2alpha injection, which initiated luteolysis and the
      development of a preovulatory follicle, moderately increased HPSE mRNA in bovine
      granulosa cells (GCs). GnRH, used to induce gonadotropin surge, markedly
      augmented HPSE mRNA levels 12 h after its injection. The temporal pattern of HPSE
      gene expression in follicular-luteal transition was further examined in follicles
      collected before, and 4, 10, 20, 25, and 60 h after GnRH injection. HPSE mRNA
      increased transiently 10-20 h after GnRH injection to levels 10-fold higher than
      in untreated heifers. HPSE protein levels were similarly elevated 20 h after GnRH
      injection in GCs, but not in the theca layer. Cyclooxygenase-2 (PTGS2) mRNA
      peaked before ovulation when HPSE levels returned to baseline levels. HPSE mRNA
      abundance also remained low in the CLs. The antiprogesterone, RU-486, elevated
      HPSE levels in GC culture, suggesting that progesterone secreted by CLs may
      inhibit HPSE. HPSE immunostaining was more abundant in GCs than thecae. In
      cultured GCs, LH induced a transient increase in HPSE mRNA 3-6 h after its
      addition, but not at 24 h. However, PTGS2 mRNA was clearly induced at this time.
      These findings suggest that: 1) HPSE may play a role in ovulation but much less
      so during CL development, and 2) GC-derived HSPE may be a novel member of the LH
      induced extracellular matrix-degrading enzyme family and may contribute to
      follicular rupture.

PMID- 18818293
TI  - Dickkopf-like1 regulates postpubertal spermatocyte apoptosis and testosterone
      production.
AB  - Dickkopf-like1 (Dkkl1) encodes a glycoprotein secreted by postmeiotic male germ
      cells. We report here that adult Dkkl1-deficient males have elevated sperm counts
      caused by a decrease in postpubertal spermatocyte apoptosis and display, upon
      aging, increased local production of testosterone. Molecular analyses identified
      the Fas death ligand (FasL) as a target for Dkkl1 pro-apoptotic activity in adult
      mice. Accordingly, adult FasL-deficient gld mice display an increased sperm count
      and decreased spermatocyte apoptosis phenotype similar to the one observed in
      Dkkl1-deficient mice. We also show that the elevated testosterone level observed
      in aging Dkkl1-deficient males is secondary to increased expression in Leydig
      cells of CYP11A and CYP17, two genes implicated in steroidogenesis. Furthermore,
      treatment of Leydig cells with Dkkl1 decreases DNA binding and transcriptional
      activity of steroidogenic factor 1, a pivotal regulator of gene expression in
      testis. Thus, this study establishes Dkkl1 as a negative regulator of adult
      testis homeostasis and identifies a novel, Dkkl1/FasL-dependent, regulation that
      specifically controls the number of postpubertal spermatocytes.

PMID- 18818294
TI  - Prostaglandin E2 acts via multiple receptors to regulate plasminogen-dependent
      proteolysis in the primate periovulatory follicle.
AB  - The ovulatory gonadotropin surge regulates expression of plasminogen activator
      (PA) family members within the ovarian follicle, which are implicated in follicle
      wall degradation at ovulation. Gonadotropin also stimulates follicular
      prostaglandin E2 (PGE2) production, which is required for follicle rupture. To
      determine whether the ovulatory gonadotropin surge regulates PA-mediated
      proteolysis via PGE2 in the primate follicle, monkeys received gonadotropins to
      stimulate follicle development. Follicular aspirates or whole ovaries were
      obtained before (0 h) and after human chorionic gonadotropin (hCG) administration
      to span the periovulatory interval. Granulosa cell levels of tissue-type PA (tPA)
      and PA inhibitor type 1 (PAI-1) proteins were low at 0 h hCG and higher after hCG
      administration. In situ zymography showed no ovarian tPA activity 0 h after hCG;
      tPA activity was present in granulosa cells obtained after hCG treatment.
      Importantly, tPA and PAI-1 proteins and tPA activity were low/nondetectable in
      granulosa cells obtained after treatment with hCG and the PG synthesis inhibitor
      celecoxib. To determine whether hCG stimulation of tPA and PAI-1 requires PGE2,
      granulosa cells obtained at 0 h were cultured with hCG plus indomethacin to
      inhibit PG production; some cells also received PGE2 or an agonist selective for
      one PGE2 receptor (EP). PGE2, an EP2 agonist, and an EP3 agonist increased tPA
      protein, whereas PGE2, an EP1 agonist, and an EP3 agonist increased PAI-1
      protein. Therefore, gonadotropin increases granulosa cell tPA and PAI-1 protein
      levels and tPA-dependent proteolytic activity. PGE2 also increases tPA and PAI-1
      protein levels in granulosa cells, suggesting that elevated PGE2 late in the
      periovulatory interval acts to stimulate proteolysis and follicle rupture.

PMID- 18818295
TI  - Gastrin-releasing peptide messenger ribonucleic acid expression in the
      hypothalamic paraventricular nucleus is altered by melanocortin receptor
      stimulation and food deprivation.
AB  - Gastrin-releasing peptide (GRP) is a bombesin-like peptide widely distributed in
      the gastrointestinal tract and central nervous system. In the brain, GRP mRNA is
      located in the hypothalamic paraventricular nucleus (PVN), a region that receives
      neural input from the arcuate nucleus and plays a critical role in food intake
      and energy balance. Because GRP neurons are localized in the vicinity of
      projection sites in the PVN for peptides that participate in energy homeostasis,
      we investigated whether GRP mRNA expression in the PVN may be sensitive to
      challenges imposed by either 38 h food deprivation or stimulation of the
      melanocortin system by the melanocortin 3/4 receptor agonist, melanotan II
      (MTII). We found that food deprivation significantly decreased GRP mRNA
      expression, whereas lateral ventricular MTII administration increased GRP mRNA
      expression in ad libitum-fed rats 4 h after administration. Furthermore,
      administration of MTII at a dose that reduces 24 h food intake and body weight
      prevented the decrease in GRP mRNA expression observed in animals that were pair
      fed to the amount of food consumed by those injected with MTII. These results
      demonstrate that food deprivation and stimulation of the melanocortin system
      produce opposing changes in GRP gene expression in the PVN, suggesting that GRP
      containing neurons in the PVN may be part of the hypothalamic signaling pathway
      controlling food intake and energy balance.

PMID- 18818296
TI  - Severe preeclampsia-related changes in gene expression at the maternal-fetal
      interface include sialic acid-binding immunoglobulin-like lectin-6 and pappalysin
      2.
AB  - Preeclampsia (PE), which affects 4-8% of human pregnancies, causes significant
      maternal and neonatal morbidity and mortality. Within the basal plate, placental
      cytotrophoblasts (CTBs) of fetal origin invade the uterus and extensively remodel
      the maternal vasculature. In PE, CTB invasion is often shallow, and vascular
      remodeling is rudimentary. To better understand possible causes, we conducted a
      global analysis of gene expression at the maternal-fetal interface in placental
      samples from women with PE (n = 12; 24-36 wk) vs. samples from women who
      delivered due to preterm labor with no evidence of infection (n = 11; 24-36 wk),
      a condition that our previous work showed is associated with normal CTB invasion.
      Using the HG-U133A&B Affymetrix GeneChip platform, and statistical significance
      set at log odds-ratio of B >0, 55 genes were differentially expressed in PE. They
      encoded proteins previously associated with PE [e.g. Flt-1 (vascular endothelial
      growth factor receptor-1), leptin, CRH, and inhibin] and novel molecules [e.g.
      sialic acid binding Ig-like lectin 6 (Siglec-6), a potential leptin receptor, and
      pappalysin-2 (PAPP-A2), a protease that cleaves IGF-binding proteins]. We used
      quantitative PCR to validate the expression patterns of a subset of the genes. At
      the protein level, we confirmed PE-related changes in the expression of Siglec-6
      and PAPP-A2, which localized to invasive CTBs and syncytiotrophoblasts. Notably,
      Siglec-6 placental expression is uniquely human, as is spontaneous PE. The
      functional significance of these novel observations may provide new insights into
      the pathogenesis of PE, and assaying the circulating levels of these proteins
      could have clinical utility for predicting and/or diagnosing PE.

PMID- 18818297
TI  - Maternal nutrient restriction between early and midgestation and its impact upon
      appetite regulation after juvenile obesity.
AB  - The impact of maternal nutrient restriction during early-to-midgestation, a
      period coinciding with early fetal brain development, on appetite regulation and
      energy balance in the offspring after juvenile obesity was examined. Pregnant
      sheep were either fed to meet fully their nutritional requirements throughout
      gestation or 50% of this amount between 30 and 80 d gestation. After weaning,
      offspring were either made obese through exposure to a sedentary obesogenic
      environment or remained lean. Maternal nutrient restriction had no effect on
      birth weight or subsequent growth. At 1 wk of age, only, gene expression for
      neuropeptide Y in the hypothalamus was reduced in nutrient-restricted offspring.
      By 1 yr of age, all O animals had increased plasma leptin, nonesterified fatty
      acids, and insulin, with the latter effect amplified in NR offspring. Fasting
      plasma glucose, triglycerides, and cortisol were unaffected by obesity. The
      entrained reduction in physical activity that led to obesity persisted when all
      animals were maintained within individual pens. However, NRO offspring exhibited
      reduced daily food intake and were, therefore, no longer in positive "energy
      balance." This adaptation was accompanied by elevated hypothalamic gene
      expression for the melanocortin-4 and insulin receptors, AMP-activated kinase,
      and acetyl coenzyme A carboxylase alpha. In conclusion, nutrient restriction
      specifically targeted over the period of early fetal brain development
      contributes to a profoundly different adaptation in energy balance after juvenile
      obesity. The extent to which this adaptive response may benefit the offspring or
      result in an exacerbated risk of type 2 diabetes remains to be established.

PMID- 18818298
TI  - Type 1 cannabinoid receptor-containing axons innervate hypophysiotropic
      thyrotropin-releasing hormone-synthesizing neurons.
AB  - Hypophysiotropic TRH-synthesizing neurons of the hypothalamic paraventricular
      nucleus (PVN) have a critical role in the regulation of the energy homeostasis
      through control of the hypothalamic-pituitary-thyroid axis. Recently,
      endocannabinoids have been shown to exert inhibitory effects on TRH neurons via
      the type 1 cannabinoid receptor (CB1). To understand the anatomical basis for
      this regulatory mechanism, we determined whether CB1 is contained in axons
      innervating hypophysiotropic TRH neurons using a recently developed antiserum
      against the C-terminal portion of mouse CB1. CB1-immunoreactive axons densely
      innervated the parvicellular subdivisions of the PVN where the hypophysiotropic
      TRH neurons are located. By double-labeling immunocytochemistry, CB1
      immunoreactive varicosities were observed in juxtaposition to the vast majority
      of TRH neurons in the PVN. At the ultrastructural level, CB1-immunoreactivity was
      observed in the preterminal portion of axons establishing both symmetric and
      asymmetric synaptic specializations with the perikarya and dendrites of TRH
      neurons in the PVN. These data demonstrate that CB1 is abundantly present in
      axons that are in synaptic association with hypophysiotropic TRH neurons,
      indicating an important role for endocannabinoids in the regulation of the
      hypothalamic-pituitary-thyroid axis. The presence of both symmetric and
      asymmetric type CB1 synapses on TRH neurons in the PVN suggests that
      endocannabinoids may influence both excitatory and inhibitory inputs of these
      neurons.

PMID- 18818299
TI  - The role of tanshinone IIA in the treatment of obesity through peroxisome
      proliferator-activated receptor gamma antagonism.
AB  - Peroxisome proliferator-activated receptor (PPAR) gamma is a nuclear receptor
      that coordinates carbohydrate and lipid metabolism, and is a therapeutic target
      for type 2 diabetes. Tanshinone IIA (Tan) is a lipophilic diterpene that is
      widely used to treat cardiovascular diseases in traditional Chinese medicine, and
      has recently been found to reduce body weight and lower blood lipids. However,
      its underlying mechanism of antiadipogenic effects remains unknown. Here, we
      report that Tan inhibits 3T3-L1 preadipocyte differentiation and transcriptional
      activities of full-length PPARgamma and PPARgamma ligand-binding domains. The
      effects of Tan are mediated through its property as a natural antagonist of
      PPARgamma (dissociation constant of an inhibitor value, 2.562 +/- 0.711 microm).
      Tan treatment reduced adipose mass and body weight, improved glucose tolerance,
      and lowered the low-density lipoprotein to high-density lipoprotein ratio without
      changing the food intake in a high-fat diet-induced obese animal model. Our
      results suggest that the combined properties of Tan in adipogenesis, glucose
      tolerance, lipogenesis, and cardiovascular protection are beneficial for treating
      diabetic patients with complex metabolic conditions, in which modulating a single
      target is often not sufficient to achieve the desired effect.

PMID- 18818300
TI  - Suppression of Notch signaling in the neonatal mouse ovary decreases primordial
      follicle formation.
AB  - Notch signaling directs cell fate during embryogenesis by influencing cell
      proliferation, differentiation, and apoptosis. Notch genes are expressed in the
      adult mouse ovary, and roles for Notch in regulating folliculogenesis are
      beginning to emerge from mouse genetic models. We investigated how Notch
      signaling might influence the formation of primordial follicles. Follicle
      assembly takes place when germ cell syncytia within the ovary break down and germ
      cells are encapsulated by pregranulosa cells. In the mouse, this occurs during
      the first 4-5 d of postnatal life. The expression of Notch family genes in the
      neonatal mouse ovary was determined through RT-PCR measurements. Jagged1, Notch2,
      and Hes1 transcripts were the most abundantly expressed ligand, receptor, and
      target gene, respectively. Jagged1 and Hey2 mRNAs were up-regulated over the
      period of follicle formation. Localization studies demonstrated that JAGGED1 is
      expressed in germ cells prior to follicle assembly and in the oocytes of
      primordial follicles. Pregranulosa cells that surround germ cell nests express
      HES1. In addition, pregranulosa cells of primordial follicles expressed NOTCH2
      and Hey2 mRNA. We used an ex vivo ovary culture system to assess the requirement
      for Notch signaling during early follicle development. Newborn ovaries cultured
      in the presence of gamma-secretase inhibitors, compounds that attenuate Notch
      signaling, had a marked reduction in primordial follicles compared with vehicle
      treated ovaries, and there was a corresponding increase in germ cells that
      remained within nests. These data support a functional role for Notch signaling
      in regulating primordial follicle formation.

PMID- 18818301
TI  - Acute pericardial tamponade due to ruptured multiloculated myocardial hydatid
      cyst.

PMID- 18818302
TI  - TRIB3 [corrected] is implicated in glucotoxicity- and endoplasmic reticulum
      stress-induced [corrected] beta-cell apoptosis.
AB  - We found that TRIB3, [corrected] an endogenous inhibitor of Akt (PKB), is
      expressed in pancreatic beta-cells. The TRIB3 [corrected] expression is
      significantly increased in islets isolated from hyperglycemic Goto-Kakizaki rats
      compared with normal glycemic controls. In vitro high glucose treatment also
      resulted in increased TRIB3 [corrected] expression in rat INS1 cells. To
      investigate the role of TRIB3 [corrected] in the regulation of beta-cell
      function, we established an INS1 stable cell line allowing inducible expression
      of TRIB3. [corrected] We demonstrated that overexpression of TRIB3 [corrected]
      mimicked the glucotoxic effects on insulin secretion and cell growth in INS1
      cells. Moreover, induction of TRIB3 [corrected] also synergistically enhanced
      high-glucose-elicited apoptosis in INS1 cells, whereas siRNA knock-down of TRIB3
      [corrected] showed the opposite effects. We also confirmed that the DeltaPsim of
      mitochondria was decreased, caspase-3 activity was up-regulated and reactive
      oxygen species content was increased in TRIB3 [corrected] overexpressing beta
      cells in high glucose condition. Most interestingly, the oestrogen receptor (ER)
      stress inducer, thapsigargin, mimicked the high glucose effects on up-regulation
      of TRIB3 [corrected] and generation of apoptosis in cultured INS1 cells. These
      effects were specifically prevented by siRNA knock down of TRIB3. [corrected] We
      therefore conclude that TRIB3 [corrected] is implicated in glucotoxicity- and ER
      stress-induced beta-cell failure.TRIB3 [corrected] could be a potential
      pharmacological target for prevention and treatment of type 2 diabetes.

PMID- 18818303
TI  - Identification and functional characterization of allosteric agonists for the G
      protein-coupled receptor FFA2.
AB  - FFA2 (GPR43) has been identified as a receptor for short-chain fatty acids
      (SCFAs) that include acetate and propionate. FFA2 is highly expressed in islets,
      a subset of immune cells, and adipocytes. Although the potential roles of FFA2
      activation in these tissues have previously been described, the physiological
      functions are still unclear. The potency for SCFAs on FFA2 is low, in the high
      micromolar to millimolar concentrations. To identify better pharmacological tools
      to study receptor function, we used high-throughput screening (HTS) to discover a
      series of small molecule phenylacetamides as novel and more potent FFA2 agonists.
      This series is specific for FFA2 over FFA1 (GPR40) and FFA3 (GPR41), and it is
      able to activate both the Galpha(q) and Galpha(i) pathways in vitro on Chinese
      hamster ovary cells stably expressing FFA2. Treatment of adipocytes with these
      compounds also resulted in Galpha(i)-dependent inhibition of lipolysis similar to
      that of endogenous ligands (SCFAs). It is noteworthy that these compounds not
      only acted as FFA2 agonists but also exhibited positive cooperativity with
      acetate or propionate. The observed allosteric modulation was consistent in all
      the functional assays that we have explored, including cAMP, calcium
      mobilization, guanosine 5'-[gamma-thio]triphosphate binding, and lipolysis.
      Molecular modeling analysis of FFA2 based on human beta(2)-adrenergic receptor
      structure revealed potential nonoverlapping binding sites for the endogenous and
      synthetic ligands, further providing insight into the binding pocket for the
      allosteric interactions. This is the first report describing the identification
      of novel allosteric modulators with agonist activity for FFA2, and these
      compounds may serve as tools for further unraveling the physiological functions
      of the receptor and its involvement in various diseases.

PMID- 18818304
TI  - Mitochondrial potassium channel Kv1.3 mediates Bax-induced apoptosis in
      lymphocytes.
AB  - The potassium channel Kv1.3 has recently been located to the inner mitochondrial
      membrane of lymphocytes. Here, we show that mouse and human cells either
      genetically deficient in Kv1.3 or transfected with siRNA to suppress Kv1.3
      expression resisted apoptosis induced by several stimuli, including Bax over
      expression [corrected]. Retransfection of either Kv1.3 or a mitochondrial
      targeted Kv1.3 restored cell death . Bax interacted with and functionally
      inhibited mitochondrial Kv1.3. Incubation of isolated Kv1.3-positive mitochondria
      with recombinant Bax, t-Bid, or toxins that bind to and inhibit Kv1.3
      successively triggered hyperpolarization, formation of reactive oxygen species,
      release of cytochrome c, and marked depolarization. Kv1.3-deficient mitochondria
      were resistant to Bax, t-Bid, and the toxins. Mutation of Bax at K128, which
      corresponds to a conserved lysine in Kv1.3-inhibiting toxins, abrogated its
      effects on both Kv1.3 and mitochondria. These findings suggest that Bax mediates
      cytochrome c release and mitochondrial depolarization in lymphocytes, at least in
      part, via its interaction with mitochondrial Kv1.3.

PMID- 18818305
TI  - New auxin analogs with growth-promoting effects in intact plants reveal a
      chemical strategy to improve hormone delivery.
AB  - Plant growth depends on the integration of environmental cues and phytohormone
      signaling pathways. During seedling emergence, elongation of the embryonic stem
      (hypocotyl) serves as a readout for light and hormone-dependent responses. We
      screened 10,000 chemicals provided exogenously to light-grown seedlings and
      identified 100 compounds that promote hypocotyl elongation. Notably, one subset
      of these chemicals shares structural characteristics with the synthetic auxins,
      2,4-dichlorophenoxyacetic acid (2,4-D), and 1-naphthaleneacetic acid (1-NAA);
      however, traditional auxins (e.g., indole-3-acetic acid [IAA], 2,4-D, 1-NAA) have
      no effect on hypocotyl elongation. We show that the new compounds act as
      "proauxins" akin to prodrugs. Our data suggest that these compounds diffuse
      efficiently to the hypocotyls, where they undergo cleavage at varying rates,
      releasing functional auxins. To investigate this principle, we applied a masking
      strategy and designed a pro-2,4-D. Unlike 2,4-D alone, this pro-2,4-D enhanced
      hypocotyl elongation. We further demonstrated the utility of the proauxins by
      characterizing auxin responses in light-grown hypocotyls of several auxin
      receptor mutants. These new compounds thus provide experimental access to a
      tissue previously inaccessible to exogenous application of auxins. Our studies
      exemplify the combined power of chemical genetics and biochemical analyses for
      discovering and refining prohormone analogs with selective activity in specific
      plant tissues. In addition to the utility of these compounds for addressing
      questions related to auxin and light-signaling interactions, one can envision
      using these simple principles to study other plant hormone and small molecule
      responses in temporally and spatially controlled ways.

PMID- 18818306
TI  - Respiratory syncytial virus impairs T cell activation by preventing synapse
      assembly with dendritic cells.
AB  - Respiratory syncytial virus (RSV) infection is one of the leading causes of
      infant hospitalization and a major health and economic burden worldwide.
      Infection with this virus induces an exacerbated innate proinflammatory immune
      response characterized by abundant immune cell infiltration into the airways and
      lung tissue damage. RSV also impairs the induction of an adequate adaptive T cell
      immune response, which favors virus pathogenesis. Unfortunately, to date there
      are no efficient vaccines against this virus. Recent in vitro and in vivo studies
      suggest that RSV infection can prevent T cell activation, a phenomenon attributed
      in part to cytokines and chemokines secreted by RSV-infected cells. Efficient
      immunity against viruses is promoted by dendritic cells (DCs), professional
      antigen-presenting cells, that prime antigen-specific helper and cytotoxic T
      cells. Therefore, it would be to the advantage of RSV to impair DC function and
      prevent the induction of T cell immunity. Here, we show that, although RSV
      infection induces maturation of murine DCs, these cells are rendered unable to
      activate antigen-specific T cells. Inhibition of T cell activation by RSV was
      observed independently of the type of TCR ligand on the DC surface and applied to
      cognate-, allo-, and superantigen stimulation. As a result of exposure to RSV
      infected DCs, T cells became unresponsive to subsequent TCR engagement. RSV
      mediated impairment in T cell activation required DC-T cell contact and involved
      inhibition of immunological synapse assembly among these cells. Our data suggest
      that impairment of immunological synapse could contribute to RSV pathogenesis by
      evading adaptive immunity and reducing T cell-mediated virus clearance.

PMID- 18818307
TI  - S4-based voltage sensors have three major conformations.
AB  - Voltage sensors containing the charged S4 membrane segment display a gating
      charge vs. voltage (Q-V) curve that depends on the initial voltage. The voltage
      dependent phosphatase (Ci-VSP), which does not have a conducting pore, shows the
      same phenomenon and the Q-V recorded with a depolarized initial voltage is more
      stable by at least 3RT. The leftward shift of the Q-V curve under prolonged
      depolarization was studied in the Ci-VSP by using electrophysiological and site
      directed fluorescence measurements. The fluorescence shows two components: one
      that traces the time course of the charge movement between the resting and active
      states and a slower component that traces the transition between the active state
      and a more stable state we call the relaxed state. Temperature dependence shows a
      large negative enthalpic change when going from the active to the relaxed state
      that is almost compensated by a large negative entropic change. The Q-V curve
      midpoint measured for pulses that move the sensor between the resting and active
      states, but not long enough to evolve into the relaxed states, show a periodicity
      of 120 degrees, indicating a 3(10) secondary structure of the S4 segment when
      determined under histidine scanning. We hypothesize that the S4 segment moves as
      a 3(10) helix between the resting and active states and that it converts to an
      alpha-helix when evolving into the relaxed state, which is most likely to be the
      state captured in the crystal structures.

PMID- 18818308
TI  - Probing atomic ordering and multiple twinning in metal nanocrystals through their
      vibrations.
AB  - Control of nanocrystal (NC) crystallinity currently raises great interest because
      of its potential benefits in both physics modeling and technological
      applications. Advances in methods for synthesizing perfect single-crystalline NCs
      are recent, so that the effect of crystallinity on NC properties has received
      only limited study and still needs to be properly investigated. Here, we report
      that crystallinity of gold NCs dramatically modifies their vibrations. Using low
      frequency Raman scattering, we clearly demonstrate that single-domain NCs vibrate
      differently than their multiply twinned counterparts, through the splitting of
      the quadrupolar vibrations, which is only observed for the former. Using the
      resonant ultrasound approach, we calculate the vibrational frequencies of a gold
      sphere and show that elastic anisotropy induces a lift of degeneracy of the
      quadrupolar mode in good agreement with our experimental measurements. These
      findings open up challenging perspectives on using Raman spectroscopy to
      characterize nanocrystallinity.

PMID- 18818309
TI  - CTLA-4 blockade increases IFNgamma-producing CD4+ICOShi cells to shift the ratio
      of effector to regulatory T cells in cancer patients.
AB  - Significant anti-tumor responses have been reported in a small subset of cancer
      patients treated with the immunotherapeutic agent anti-CTLA-4 antibody. All
      clinical trials to date, comprising over 3,000 patients, have been conducted in
      the metastatic disease setting, which allows for correlation of drug
      administration with clinical outcome but has limited analyses of intermediate
      biomarkers to indicate whether the drug has impacted human immune responses
      within the tumor microenvironment. We conducted a pre-surgical clinical trial in
      six patients with localized bladder cancer, which allowed for correlation of drug
      administration with biomarkers in both blood and tumor tissues but did not permit
      correlation with clinical outcome. We found that CD4 T cells from peripheral
      blood and tumor tissues of all treated patients had markedly increased expression
      of inducible costimulator (ICOS). These CD4(+)ICOS(hi) T cells produced IFN-gamma
      (IFNgamma) and could recognize the tumor antigen NY-ESO-1. Increase in
      CD4(+)ICOS(hi) cells led to an increase in the ratio of effector to regulatory T
      cells. To our knowledge, these are the first immunologic changes reported in both
      tumor tissues and peripheral blood as a result of treatment with anti-CTLA-4
      antibody, and they may be used to guide dosing and scheduling of this agent to
      improve clinical responses.

PMID- 18818310
TI  - AP4 encodes a c-MYC-inducible repressor of p21.
AB  - In the majority of human tumors, expression of the c-MYC oncogene becomes
      constitutive. Here, we report that c-MYC directly regulates the expression of AP4
      via CACGTG motifs in the first intron of the AP4 gene. Induction of AP4 was
      required for c-MYC-mediated cell cycle reentry of anti-estrogen arrested breast
      cancer cells and mitogen-mediated repression of the CDK inhibitor p21. AP4
      directly repressed p21 by occupying four CAGCTG motifs in the p21 promoter via
      its basic region. AP4 levels declined after DNA damage, and ectopic AP4
      interfered with p53-mediated cell cycle arrest and sensitized cells to apoptosis
      induced by DNA damaging agents. AP4 expression blocked induction of p21 by TGF
      beta in human keratinocytes and interfered with up-regulation of p21 and cell
      cycle arrest during monoblast differentiation. Notably, AP4 is specifically
      expressed in colonic progenitor and colorectal carcinoma cells. In conclusion,
      our results indicate that c-MYC employs AP4 to maintain cells in a proliferative,
      progenitor-like state.

PMID- 18818311
TI  - Precision proteomics: the case for high resolution and high mass accuracy.
AB  - Proteomics has progressed radically in the last 5 years and is now on par with
      most genomic technologies in throughput and comprehensiveness. Analyzing peptide
      mixtures by liquid chromatography coupled to high-resolution mass spectrometry
      (LC-MS) has emerged as the main technology for in-depth proteome analysis whereas
      two-dimensional gel electrophoresis, low-resolution MALDI, and protein arrays are
      playing niche roles. MS-based proteomics is rapidly becoming quantitative through
      both label-free and stable isotope labeling technologies. The latest generation
      of mass spectrometers combines extremely high resolving power, mass accuracy, and
      very high sequencing speed in routine proteomic applications. Peptide
      fragmentation is mostly performed in low-resolution but very sensitive and fast
      linear ion traps. However, alternative fragmentation methods and high-resolution
      fragment analysis are becoming much more practical. Recent advances in
      computational proteomics are removing the data analysis bottleneck. Thus, in a
      few specialized laboratories, "precision proteomics" can now identify and
      quantify almost all fragmented peptide peaks. Huge challenges and opportunities
      remain in technology development for proteomics; thus, this is not "the beginning
      of the end" but surely "the end of the beginning."

PMID- 18818312
TI  - Identification of amino acids essential for the antiangiogenic activity of
      tumstatin and its use in combination antitumor activity.
AB  - Tumstatin is an angiogenesis inhibitor that binds to alphavbeta3 integrin and
      suppresses tumor growth. Previous deletion mutagenesis studies identified a 25-aa
      fragment of tumstatin (tumstatin peptide) with in vitro antiangiogenic activity.
      Here, we demonstrate that systemic administration of this tumstatin peptide
      inhibits tumor growth and angiogenesis. Site-directed mutagenesis identified
      amino acids L, V, and D as essential for the antiangiogenic activity of
      tumstatin. The tumstatin peptide binds to alphavbeta3 integrin on proliferating
      endothelial cells and localizes to select tumor endothelium in vivo. Using 3D
      molecular modeling, we identify a putative interaction interface for tumstatin
      peptide on alphavbeta3 integrin. The antitumor activity of the tumstatin peptide,
      in combination with bevacizumab (anti-VEGF antibody), displays significant
      improvement in efficacy against human renal cell carcinoma xenografts when
      compared with the single-agent use. Collectively, our results demonstrate that
      tumstatin peptide binds specifically to the tumor endothelium, and its
      antiangiogenic action is mediated by alphavbeta3 integrin, and, in combination
      with an anti-VEGF antibody it exhibits enhanced tumor suppression of renal cell
      carcinoma.

PMID- 18818313
TI  - The steady-state level of Mg-protoporphyrin IX is not a determinant of plastid-to
      nucleus signaling in Arabidopsis.
AB  - The plastid plays a vital role in various cellular activities within plant cells
      including photosynthesis and other metabolic pathways. It is believed that the
      functional status of the plastid is somehow monitored by the nucleus to optimize
      the expression of genes encoding plastid proteins. The currently dominant model
      for plastid-derived signaling ("plastid signaling") proposes that Mg
      protoporphyrin IX (MgProto) is a negative signal that represses the expression of
      a wide range of nuclear genes encoding plastid-localized proteins when plastid
      development is inhibited. In this study, we have re-evaluated this hypothesis by
      quantifying the steady-state levels of MgProto (as well as its neighboring
      intermediates protoporphyrin IX and Mg-Proto monomethyl ester [MgProtoMe]) in
      Arabidopsis plants with altered plastid signaling responses as monitored by
      expression of the Lhcb1, RBCS, HEMA1, BAM3 and CA1 genes. In addition, we have
      examined the correlation between gene expression and MgProto (MgProtoMe) in a
      range of mutants and conditions in which the steady-state levels of MgProto
      (MgProtoMe) have been modified. Overall we found that there was no correlation
      between the steady-state levels of MgProto (MgProtoMe) and Lhcb1 expression or
      with any of the other genes tested. Taking these results together, we propose
      that the current model on plastid signaling must be revised.

PMID- 18818314
TI  - Tetrapyrrole profiling in Arabidopsis seedlings reveals that retrograde plastid
      nuclear signaling is not due to Mg-protoporphyrin IX accumulation.
AB  - Chloroplast biogenesis involves careful coordination of both plastid and nuclear
      gene expression, which is achieved in part by retrograde signaling from the
      chloroplast to the nucleus. This can be demonstrated by the fact that the
      herbicide, Norflurazon (NF), which causes bleaching of chloroplasts, prevents the
      light induction of photosynthesis-related genes in the nucleus. It has been
      proposed that the tetrapyrrole pathway intermediate Mg-protoporphyrin IX acts as
      the signaling molecule in this pathway and accumulates in the chloroplasts and
      cytosol of the cell after NF treatment. Here we present data that demonstrate
      that this model is too simplistic. We have developed a sensitive liquid
      chromatography-mass spectrometry (LC/MS) method to measure tetrapyrrole
      intermediates and have shown that no Mg-protoporphyrin IX, nor indeed any other
      chlorophyll-biosynthesis intermediate, can be detected in NF-treated plants under
      conditions in which nuclear gene expression is repressed. Conversely when
      endogenous Mg-protoporphyrin IX levels are artificially increased by
      supplementation with the tetrapyrrole precursor, 5-aminolevulinic acid, the
      expression of nuclear-encoded photosynthetic genes is induced, not repressed. We
      also demonstrate that NF-treatment leads to a strong down-regulation of
      tetrapyrrole biosynthesis genes, consistent with the absence of an accumulation
      of tetrapyrrole intermediates. Finally, there is no correlation between nuclear
      gene expression and any of the chlorophyll biosynthetic intermediates over a
      range of growth conditions and treatments. Instead, it is possible that a
      perturbation of tetrapyrrole synthesis may lead to localized ROS production or an
      altered redox state of the plastid, which could mediate retrograde signaling.

PMID- 18818317
TI  - Enteral feeding induces diet-dependent mucosal dysfunction, bacterial
      proliferation, and necrotizing enterocolitis in preterm pigs on parenteral
      nutrition.
AB  - Preterm neonates have an immature gut and metabolism and may benefit from total
      parenteral nutrition (TPN) before enteral food is introduced. Conversely, delayed
      enteral feeding may inhibit gut maturation and sensitize to necrotizing
      enterocolitis (NEC). Intestinal mass and NEC lesions were first recorded in
      preterm pigs fed enterally (porcine colostrum, bovine colostrum, or formula for
      20-40 h), with or without a preceding 2- to 3-day TPN period (n = 435). Mucosal
      mass increased during TPN and further after enteral feeding to reach an
      intestinal mass similar to that in enterally fed pigs without TPN (+60-80%
      relative to birth). NEC developed only after enteral feeding but more often after
      a preceding TPN period for both sow's colostrum (26 vs. 5%) and formula (62 vs.
      39%, both P < 0.001, n = 43-170). Further studies in 3-day-old TPN pigs fed
      enterally showed that formula feeding decreased villus height and nutrient
      digestive capacity and increased luminal lactic acid and NEC lesions, compared
      with colostrum (bovine or porcine, P < 0.05). Mucosal microbial diversity
      increased with enteral feeding, and Clostridium perfringens density was related
      to NEC severity. Formula feeding decreased plasma arginine, citrulline,
      ornithine, and tissue antioxidants, whereas tissue nitric oxide synthetase and
      gut permeability increased, relative to colostrum (all P < 0.05). In conclusion,
      enteral feeding is associated with gut dysfunction, microbial imbalance, and NEC
      in preterm pigs, especially in pigs fed formula after TPN. Conversely, colostrum
      milk diets improve gut maturation and NEC resistance in preterm pigs subjected to
      a few days of TPN after birth.

PMID- 18818315
TI  - Involvement of a Stat3 binding site in inflammation-induced enteric apelin
      expression.
AB  - Apelin is the endogenous ligand for the APJ receptor; both are expressed in the
      gastrointestinal tract. Experimental colitis in rodents and inflammatory bowel
      disease in humans are associated with increased intestinal apelin production. Our
      aim was to use LPS and proinflammatory cytokine-treated (IL-6 and IFN-gamma)
      rodents or enteric cells to identify signaling mechanisms underlying inflammation
      induced enteric apelin expression. LPS, IL-6, or IFN-gamma treatment of rodents
      increased enteric apelin expression. Pharmacological blockade of Jak/Stat
      signaling or IL-6 antibody administration inhibited elevations in enteric apelin
      expression. Transient transfection experiments showed that LPS, IL-6, or IFN
      gamma increased apelin expression by stimulation of apelin promoter activity, and
      blockade of Jak/Stat signaling abolished elevations in apelin promoter activity.
      A chromatin immunoprecipitation assay showed that IL-6 induced binding of phospho
      Stat3 to a putative Stat3 site in the apelin promoter; mutation of this site
      abrogated the LPS-induced elevation in apelin promoter activity. Together, our
      findings indicate that binding of phospho-Stat3 to the apelin promoter is the
      final step underlying proinflammatory cytokine-induced enteric apelin expression
      during intestinal inflammation.

PMID- 18818316
TI  - Limited effects of dietary curcumin on Th-1 driven colitis in IL-10 deficient
      mice suggest an IL-10-dependent mechanism of protection.
AB  - Curcumin (diferulolylmethane) demonstrates profound anti-inflammatory effects in
      intestinal epithelial cells (IEC) and in immune cells in vitro and exhibits a
      protective role in rodent models of chemically induced colitis, with its presumed
      primary mechanism of action via inhibition of NF-kappaB. Although it has been
      demonstrated effective in reducing relapse rate in ulcerative colitis patients,
      curcumin's effectiveness in Crohn's disease (CD) or in Th-1/Th-17 mediated immune
      models of CD has not been evaluated. Therefore, we investigated the effects of
      dietary curcumin (0.1-1%) on the development of colitis, immune activation, and
      in vivo NF-kappaB activity in germ-free IL-10(-/-) or IL-10(-/-);NF-kappaB(EGFP)
      mice colonized with specific pathogen-free microflora. Proximal and distal colon
      morphology showed a mild protective effect of curcumin only at 0.1%. Colonic IFN
      gamma and IL-12/23p40 mRNA expression followed similar pattern ( approximately
      50% inhibition at 0.1%). Secretion of IL-12/23p40 and IFN-gamma by colonic
      explants and mesenteric lymph node cells was elevated in IL-10(-/-) mice and was
      not decreased by dietary curcumin. Surprisingly, activation of NF-kappaB in IL
      10(-/-) mice (phospho-NF-kappaBp65) or in IL-10(-/-);NF-kappaB(EGFP) mice (whole
      organ or confocal imaging) was not noticeably inhibited by curcumin. Furthermore,
      we demonstrate that IL-10 and curcumin act synergistically to downregulate NF
      kappaB activity in IEC and IL-12/23p40 production by splenocytes and dendritic
      cells. In conclusion, curcumin demonstrates limited effectiveness on Th-1
      mediated colitis in IL-10(-/-) mice, with moderately improved colonic morphology,
      but with no significant effect on pathogenic T cell responses and in situ NF
      kappaB activity. In vitro studies suggest that the protective effects of curcumin
      are IL-10 dependent.

PMID- 18818318
TI  - Primary clearance of murine gammaherpesvirus 68 by PKCtheta-/- CD8 T cells is
      compromised in the absence of help from CD4 T cells.
AB  - CD4 T cells are dispensable for acute control of murine gammaherpesvirus 68 (MHV
      68) but are necessary for effective long-term control of the virus by CD8 T
      cells. In contrast, protein kinase C theta (PKCtheta) is not essential for either
      acute or long-term viral control. However, we found that while either CD4 or CD8
      T cells could mediate the clearance of MHV-68 from the lungs of PKCtheta(+/+)
      mice, PKCtheta(-/-) mice depleted of either subset failed to clear the virus.
      These data suggest that there are two alternative pathways for MHV-68 clearance,
      one dependent on CD4 T cells and the other on PKCtheta. Protection mediated by
      the latter appears to be short-lived. These observations may help to explain the
      differential requirement for PKCtheta in various models of CD8 T-cell activation
      and differences in the costimulatory requirements for acute and long-term viral
      control.

PMID- 18818319
TI  - Identification of a movement protein of the tenuivirus rice stripe virus.
AB  - Rice stripe virus (RSV) is the type member of the genus Tenuivirus. RSV has four
      single-stranded RNAs and causes severe disease in rice fields in different parts
      of China. To date, no reports have described how RSV spreads within host plants
      or the viral and/or host factor(s) required for tenuivirus movement. We
      investigated functions of six RSV-encoded proteins using trans-complementation
      experiments and biolistic bombardment. We demonstrate that NSvc4, encoded by RSV
      RNA4, supports the intercellular trafficking of a movement-deficient Potato virus
      X in Nicotiana benthamiana leaves. We also determined that upon biolistic
      bombardment or agroinfiltration, NSvc4:enhanced green fluorescent protein (eGFP)
      fusion proteins localize predominantly near or within the walls of onion and
      tobacco epidermal cells. In addition, the NSvc4:eGFP fusion protein can move from
      initially bombarded cells to neighboring cells in Nicotiana benthamiana leaves.
      Immunocytochemistry using tissue sections from RSV-infected rice leaves and an
      RSV NSvc4-specific antibody showed that the NSvc4 protein accumulated in walls of
      RSV-infected leaf cells. Gel retardation assays revealed that the NSvc4 protein
      interacts with single-stranded RNA in vitro, a common feature of many reported
      plant viral movement proteins (MPs). RSV NSvc4 failed to interact with the RSV
      nucleocapsid protein using yeast two-hybrid assays. Taken together, our data
      indicate that RSV NSvc4 is likely an MP of the virus. This is the first report
      describing a tenuivirus MP.

PMID- 18818320
TI  - Systematic assembly of a full-length infectious clone of human coronavirus NL63.
AB  - Historically, coronaviruses were predominantly associated with mild upper
      respiratory disease in humans. More recently, three novel coronaviruses
      associated with severe human respiratory disease were found, including (i) the
      severe acute respiratory syndrome coronavirus, associated with a significant
      atypical pneumonia and 10% mortality; (ii) HKU-1, associated with chronic
      pulmonary disease; and (iii) NL63, associated with both upper and lower
      respiratory tract disease in children and adults worldwide. These discoveries
      establish coronaviruses as important human pathogens and underscore the need for
      continued research toward the development of platforms that will enable genetic
      manipulation of the viral genome, allowing for rapid and rational development and
      testing of candidate vaccines, vaccine vectors, and therapeutics. In this report,
      we describe a reverse genetics system for NL63, whereby five contiguous cDNAs
      that span the entire genome were used to generate a full-length cDNA. Recombinant
      NL63 viruses which contained the expected marker mutations replicated as
      efficiently as the wild-type NL63 virus. In addition, we engineered the
      heterologous green fluorescent protein gene in place of open reading frame 3
      (ORF3) of the NL63 clone, simultaneously creating a unique marker for NL63
      infection and demonstrating that the ORF3 protein product is nonessential for the
      replication of NL63 in cell culture. The availability of the NL63 and NL63gfp
      clones and recombinant viruses provides powerful tools that will help advance our
      understanding of this important human pathogen.

PMID- 18818321
TI  - Points of recombination in Epstein-Barr virus (EBV) strain P3HR-1-derived
      heterogeneous DNA as indexes to EBV DNA recombinogenic events in vivo.
AB  - Deletions and rearrangements in the genome of Epstein-Barr virus (EBV) strain
      P3HR-1 generate subgenomic infectious particles that, unlike defective
      interfering particles in other viral systems, enhance rather than restrict EBV
      replication in vitro. Reports of comparable heterogeneous (het) DNA in EBV-linked
      human diseases, based on detection of an abnormal juxtaposition of EBV DNA
      fragments BamHI W and BamHI Z that disrupts viral latency, prompted us to
      determine at the nucleotide level all remaining recombination joints formed by
      the four constituent segments of P3HR-1-derived het DNA. Guided by endonuclease
      restriction maps, we chose PCR primer pairs that approximated and framed
      junctions creating the unique BamHI M/B1 and E/S fusion fragments. Sequencing of
      PCR products revealed points of recombination that lacked regions of extensive
      homology between constituent fragments. Identical recombination junctions were
      detected by PCR in EBV-positive salivary samples from human immunodeficiency
      virus-infected donors, although the W/Z rearrangement that induces EBV
      reactivation was frequently found in the absence of the other two. In vitro
      infection of lymphoid cells similarly indicated that not all three het DNA
      rearrangements need to reside on a composite molecule. These results connote a
      precision in the recombination process that dictates both composition and
      regulation of gene segments altered by genomic rearrangement. Moreover, the
      apparent frequency of het DNA at sites of EBV replication in vivo is consistent
      with a likely contribution to the pathogenesis of EBV reactivation.

PMID- 18818323
TI  - RNA interference inhibits respiratory syncytial virus replication and disease
      pathogenesis without inhibiting priming of the memory immune response.
AB  - Respiratory syncytial virus (RSV) is a major cause of morbidity in infants, young
      children, and the elderly worldwide. Currently, there is no effective vaccine,
      and antiviral drugs to control infection are limited. RNA interference is a
      powerful tool amenable to development of antiviral drugs. Using small interfering
      RNA (siRNA) targeting the RSV P gene (siRNA-P), RSV replication can be silenced
      both in vitro and in a BALB/c model of RSV infection. In this study, we examine
      the effect of siRNA prophylaxis on the primary and memory immune response to RSV
      infection in mice. We show that mice prophylactically treated with siRNA-P to
      decrease but not eliminate RSV replication exhibit reduced pulmonary inflammation
      and lung pathogenesis and produce a robust anti-RSV memory response when
      subsequently challenged with RSV. The pulmonary T-cell memory response was
      characterized by high numbers of CD44(hi) CD62L(lo) CD4(+) and CD8(+) T cells, M2
      peptide tetramer(+) CD8(+) T cells expressing gamma interferon, and an RSV
      specific antibody response. The results support the hypothesis that siRNAs can be
      developed as effective antiviral drugs that can be used to reduce the viral load
      and parameters of pathogenesis without limiting the induction of the memory
      immune response.

PMID- 18818322
TI  - Cell-restricted immortalization by human papillomavirus correlates with
      telomerase activation and engagement of the hTERT promoter by Myc.
AB  - The high-risk human papillomaviruses (HPVs) are the causative agents of nearly
      all cervical cancers and are etiologically linked to additional human cancers,
      including those of anal, oral, and laryngeal origin. The main transforming genes
      of the high-risk HPVs are E6 and E7. E6, in addition to its role in p53
      degradation, induces hTERT mRNA transcription in genital keratinocytes via
      interactions with Myc protein, thereby increasing cellular telomerase activity.
      While the HPV type 16 E6 and E7 genes efficiently immortalize human
      keratinocytes, they appear to only prolong the life span of human fibroblasts. To
      examine the molecular basis for this cell-type dependency, we examined the
      correlation between the ability of E6 to transactivate endogenous and exogenous
      hTERT promoters and to immortalize genital keratinocytes and fibroblasts.
      Confirming earlier studies, the E6 and E7 genes were incapable of immortalizing
      human fibroblasts but did delay senescence. Despite the lack of immortalization,
      E6 was functional in the fibroblasts, mediating p53 degradation and strongly
      transactivating an exogenous hTERT promoter. However, E6 failed to transactivate
      the endogenous hTERT promoter. Coordinately with this failure, we observed that
      Myc protein was not associated with the endogenous hTERT promoter, most likely
      due to the extremely low level of Myc expression in these cells and/or to
      differences in chromatin structure, in contrast with hTERT promoters that we
      found to be activated by E6 (i.e., the endogenous hTERT promoter in primary
      keratinoctyes and the exogenous hTERT core promoter in fibroblasts), where Myc is
      associated with the promoter in either a quiescent or an E6-induced state. These
      findings are consistent with those of our previous studies on mutagenesis and the
      knockdown of small interfering RNA, which demonstrated a requirement for Myc in
      the induction of the hTERT promoter by E6 and suggested that occupancy of the
      promoter by Myc determines the responsiveness of E6 and the downstream induction
      of telomerase and cell immortalization.

PMID- 18818324
TI  - Equine infectious anemia virus resists the antiretroviral activity of equine
      APOBEC3 proteins through a packaging-independent mechanism.
AB  - Equine infectious anemia virus (EIAV), uniquely among lentiviruses, does not
      encode a vif gene product. Other lentiviruses, including human immunodeficiency
      virus type 1 (HIV-1), use Vif to neutralize members of the APOBEC3 (A3) family of
      intrinsic immunity factors that would otherwise inhibit viral infectivity. This
      suggests either that equine cells infected by EIAV in vivo do not express active
      A3 proteins or that EIAV has developed a novel mechanism to avoid inhibition by
      equine A3 (eA3). Here, we demonstrate that horses encode six distinct A3
      proteins, four of which contain a single copy of the cytidine deaminase (CDA)
      consensus active site and two of which contain two CDA motifs. This represents a
      level of complexity previously seen only in primates. Phylogenetic analysis of
      equine single-CDA A3 proteins revealed two proteins related to human A3A (hA3A),
      one related to hA3C, and one related to hA3H. Both equine double-CDA proteins are
      similar to hA3F and were named eA3F1 and eA3F2. Analysis of eA3F1 and eA3F2
      expression in vivo shows that the mRNAs encoding these proteins are widely
      expressed, including in cells that are natural EIAV targets. Both eA3F1 and eA3F2
      inhibit retrotransposon mobility, while eA3F1 is a potent inhibitor of a Vif
      deficient HIV-1 mutant and induces extensive editing of HIV-1 reverse
      transcripts. However, both eA3F1 and eA3F2 are weak inhibitors of EIAV.
      Surprisingly, eA3F1 and eA3F2 were packaged into EIAV and HIV-1 virions as
      effectively as hA3G, although only the latter inhibited EIAV infectivity.
      Moreover, all three proteins bound both the HIV-1 and EIAV nucleocapsid protein
      specifically in vitro. It therefore appears that EIAV has evolved a novel
      mechanism to specifically neutralize the biological activities of the cognate
      eA3F1 and eA3F2 proteins at a step subsequent to virion incorporation.

PMID- 18818325
TI  - If all you do is vote ...

PMID- 18818326
TI  - Science education. Misjudged talk opens creationist rift at Royal Society.

PMID- 18818327
TI  - Particle physics. After spectacular start, the LHC injures itself.

PMID- 18818328
TI  - Space science. Rising costs could delay NASA's next mission to Mars and future
      launches.

PMID- 18818329
TI  - Geochemistry. Geologists find vestige of early Earth--maybe world's oldest rock.

PMID- 18818330
TI  - John Beddington interview. U.K. science adviser makes his U.S. debut. Interview
      by Daniel Clery.

PMID- 18818331
TI  - Geophysics. Solid rock imposes its will on a core's magnetic dynamo.

PMID- 18818332
TI  - Proteomics. Proteomics ponders prime time.

PMID- 18818333
TI  - Proteomics. Will biomarkers take off at last?

PMID- 18818334
TI  - Election 2008. Scientists strive for a seat at the table of each campaign.

PMID- 18818335
TI  - Aging. Searching for the secrets of the super old.

PMID- 18818336
TI  - 2008 Visualization Challenge.

PMID- 18818337
TI  - 2008 Visualization Challenge winners.

PMID- 18818338
TI  - Fixing the leaky faucet.

PMID- 18818339
TI  - Redefining academic success.

PMID- 18818340
TI  - Caught in the middle?

PMID- 18818341
TI  - Just give them fellowships.

PMID- 18818342
TI  - Destabilizing the pyramid scheme.

PMID- 18818343
TI  - Biotechnology innovation in Africa.

PMID- 18818344
TI  - Assessment. School performance will fail to meet legislated benchmarks.

PMID- 18818345
TI  - Physics. For quantum information, two wrongs can make a right.

PMID- 18818346
TI  - Planetary science. The past Martian dynamo.

PMID- 18818347
TI  - Cancer. The metastasis cascade.

PMID- 18818348
TI  - Social science. Unlocking the potential of the spoken word.

PMID- 18818349
TI  - Economics. Can neural data improve economics?

PMID- 18818350
TI  - Chemistry. Nonlinear thinking about molecular energy transfer.

PMID- 18818351
TI  - Assembling materials with DNA as the guide.
AB  - DNA's remarkable molecular recognition properties and structural features make it
      one of the most promising templates to pattern materials with nanoscale
      precision. The emerging field of DNA nanotechnology strips this molecule from any
      preconceived biological role and exploits its simple code to generate addressable
      nanostructures in one, two, and three dimensions. These structures have been used
      to precisely position proteins, nanoparticles, transition metals, and other
      functional components into deliberately designed patterns. They can also act as
      templates for the growth of nanowires, aid in the structural determination of
      proteins, and provide new platforms for genomics applications. The field of DNA
      nanotechnology is growing in a number of directions, carrying with it the promise
      to substantially affect materials science and biology.

PMID- 18818352
TI  - Magnetic source separation in Earth's outer core.
AB  - We present evidence that the source of Earth's axial dipole field is largely
      independent from the sources responsible for the rest of the geomagnetic field,
      the so-called nonaxial dipole (NAD) field. Support for this claim comes from
      correlations between the structure of the historic field and the behavior of the
      paleomagnetic field recorded in precisely dated lavas at those times when the
      axial dipole was especially weak or nearly absent. It is argued that a
      "stratification" of magnetic sources exists in the fluid core such that the axial
      dipole is the only observed field component that is nearly immune from the
      influence exerted by the lowermost mantle. It follows that subsequent work on
      spherical harmonic-based field descriptions may now incorporate an understanding
      of a dichotomy of spatial-temporal dynamo processes.

PMID- 18818353
TI  - Synthesis and solid-state NMR structural characterization of 13C-labeled graphite
      oxide.
AB  - The detailed chemical structure of graphite oxide (GO), a layered material
      prepared from graphite almost 150 years ago and a precursor to chemically
      modified graphenes, has not been previously resolved because of the pseudo-random
      chemical functionalization of each layer, as well as variations in exact
      composition. Carbon-13 (13C) solid-state nuclear magnetic resonance (SSNMR)
      spectra of GO for natural abundance 13C have poor signal-to-noise ratios.
      Approximately 100% 13C-labeled graphite was made and converted to 13C-labeled GO,
      and 13C SSNMR was used to reveal details of the chemical bonding network,
      including the chemical groups and their connections. Carbon-13-labeled graphite
      can be used to prepare chemically modified graphenes for 13C SSNMR analysis with
      enhanced sensitivity and for fundamental studies of 13C-labeled graphite and
      graphene.

PMID- 18818354
TI  - Linear response breakdown in solvation dynamics induced by atomic electron
      transfer reactions.
AB  - The linear response (LR) approximation, which predicts identical relaxation rates
      from all nonequilibrium initial conditions that relax to the same equilibrium
      state, underlies dominant models of how solvation influences chemical reactivity.
      We experimentally tested the validity of LR for the solvation that accompanies
      partial electron transfer to and from a monatomic solute in solution. We
      photochemically prepared the species with stoichiometry Na0 in liquid
      tetrahydrofuran by both adding an electron to Na+ and removing an electron from
      Na-. Because atoms lack nuclear degrees of freedom, ultrafast changes in the Na0
      absorption spectrum reflected the solvation that began from our two initial
      nonequilibrium conditions. We found that the solvation of Na0 occurs more rapidly
      from Na+ than Na-, constituting a breakdown of LR. This indicates that Marcus
      theory would fail to describe electron-transfer processes for this and related
      chemical systems.

PMID- 18818355
TI  - Mars' paleomagnetic field as the result of a single-hemisphere dynamo.
AB  - Mars' crustal magnetic field was most likely generated by dynamo action in the
      planet's early history. Unexplained characteristics of the field include its
      strength, concentration in the southern hemisphere, and lack of correlation with
      any surface features except for the hemispheric crustal dichotomy. We used
      numerical dynamo modeling to demonstrate that the mechanisms proposed to explain
      crustal dichotomy formation can result in a single-hemisphere dynamo. This dynamo
      produces strong magnetic fields in only the southern hemisphere. This magnetic
      field morphology can explain why Mars' crustal magnetic field intensities are
      substantially stronger in the southern hemisphere without relying on any
      postdynamo mechanisms.

PMID- 18818356
TI  - The structure and dynamics of mid-ocean ridge hydrothermal systems.
AB  - Sub-seafloor hydrothermal convection at mid-ocean ridges transfers 25% of the
      Earth's heat flux and can form massive sulfide ore deposits. Their three
      dimensional (3D) structure and transient dynamics are uncertain. Using 3D
      numerical simulations, we demonstrated that convection cells self-organize into
      pipelike upflow zones surrounded by narrow zones of focused and relatively warm
      downflow. This configuration ensures optimal heat transfer and efficient metal
      leaching for ore-deposit formation. Simulated fluid-residence times are as short
      as 3 years. The concentric flow geometry results from nonlinearities in fluid
      properties, and this may influence the behavior of other fluid-flow systems in
      Earth's crust.

PMID- 18818357
TI  - Neodymium-142 evidence for Hadean mafic crust.
AB  - Neodymium-142 data for rocks from the Nuvvuagittuq greenstone belt in northern
      Quebec, Canada, show that some rock types have lower 142Nd/144Nd ratios than the
      terrestrial standard (epsilon142Nd = -0.07 to -0.15). Within a mafic amphibolite
      unit, 142Nd/144Nd ratios correlate positively with Sm/Nd ratios and produce a
      146Sm-142Nd isochron with an age of 4280(-81)(+53) million years. These rocks
      thus sample incompatible-element-enriched material formed shortly after Earth
      formation and may represent the oldest preserved crustal section on Earth.

PMID- 18818358
TI  - Infants' perseverative search errors are induced by pragmatic misinterpretation.
AB  - Having repeatedly retrieved an object from a location, human infants tend to
      search the same place even when they observe the object being hidden at another
      location. This perseverative error is usually explained by infants' inability to
      inhibit a previously rewarded search response or to recall the new location. We
      show that the tendency to commit this error is substantially reduced (from 81 to
      41%) when the object is hidden in front of 10-month-old infants without the
      experimenter using the communicative cues that normally accompany object hiding
      in this task. We suggest that this improvement is due to an interpretive bias
      that normally helps infants learn from demonstrations but misleads them in the
      context of a hiding game. Our finding provides an alternative theoretical
      perspective on the nature of infants' perseverative search errors.

PMID- 18818359
TI  - Antigen recognition by variable lymphocyte receptors.
AB  - Variable lymphocyte receptors (VLRs) rather than antibodies play the primary role
      in recognition of antigens in the adaptive immune system of jawless vertebrates.
      Combinatorial assembly of leucine-rich repeat (LRR) gene segments achieves the
      required repertoire for antigen recognition. We have determined a crystal
      structure for a VLR-antigen complex, VLR RBC36 in complex with the H-antigen
      trisaccharide from human blood type O erythrocytes, at 1.67 angstrom resolution.
      RBC36 binds the H-trisaccharide on the concave surface of the LRR modules of the
      solenoid structure where three key hydrophilic residues, multiple van der Waals
      interactions, and the highly variable insert of the carboxyl-terminal LRR module
      determine antigen recognition and specificity. The concave surface assembled from
      the most highly variable regions of the LRRs, along with diversity in the
      sequence and length of the highly variable insert, can account for the
      recognition of diverse antigens by VLRs.

PMID- 18818360
TI  - Disruption of the CFTR gene produces a model of cystic fibrosis in newborn pigs.
AB  - Almost two decades after CFTR was identified as the gene responsible for cystic
      fibrosis (CF), we still lack answers to many questions about the pathogenesis of
      the disease, and it remains incurable. Mice with a disrupted CFTR gene have
      greatly facilitated CF studies, but the mutant mice do not develop the
      characteristic manifestations of human CF, including abnormalities of the
      pancreas, lung, intestine, liver, and other organs. Because pigs share many
      anatomical and physiological features with humans, we generated pigs with a
      targeted disruption of both CFTR alleles. Newborn pigs lacking CFTR exhibited
      defective chloride transport and developed meconium ileus, exocrine pancreatic
      destruction, and focal biliary cirrhosis, replicating abnormalities seen in
      newborn humans with CF. The pig model may provide opportunities to address
      persistent questions about CF pathogenesis and accelerate discovery of strategies
      for prevention and treatment.

PMID- 18818361
TI  - The coevolution of cultural groups and ingroup favoritism.
AB  - Cultural boundaries have often been the basis for discrimination, nationalism,
      religious wars, and genocide. Little is known, however, about how cultural groups
      form or the evolutionary forces behind group affiliation and ingroup favoritism.
      Hence, we examine these forces experimentally and show that arbitrary symbolic
      markers, though initially meaningless, evolve to play a key role in cultural
      group formation and ingroup favoritism because they enable a population of
      heterogeneous individuals to solve important coordination problems. This process
      requires that individuals differ in some critical but unobservable way and that
      their markers be freely and flexibly chosen. If these conditions are met, markers
      become accurate predictors of behavior. The resulting social environment includes
      strong incentives to bias interactions toward others with the same marker, and
      subjects accordingly show strong ingroup favoritism. When markers do not acquire
      meaning as accurate predictors of behavior, players show a markedly reduced taste
      for ingroup favoritism. Our results support the prominent evolutionary hypothesis
      that cultural processes can reshape the selective pressures facing individuals
      and so favor the evolution of behavioral traits not previously advantaged.

PMID- 18818362
TI  - Understanding overbidding: using the neural circuitry of reward to design
      economic auctions.
AB  - We take advantage of our knowledge of the neural circuitry of reward to
      investigate a puzzling economic phenomenon: Why do people overbid in auctions?
      Using functional magnetic resonance imaging (fMRI), we observed that the social
      competition inherent in an auction results in a more pronounced blood oxygen
      level-dependent (BOLD) response to loss in the striatum, with greater overbidding
      correlated with the magnitude of this response. Leveraging these neuroimaging
      results, we design a behavioral experiment that demonstrates that framing an
      experimental auction to emphasize loss increases overbidding. These results
      highlight a role for the contemplation of loss in understanding the tendency to
      bid "too high." Current economic theories suggest overbidding may result from
      either "joy of winning" or risk aversion. By combining neuroeconomic and
      behavioral economic techniques, we find that another factor, namely loss
      contemplation in a social context, may mediate overbidding in auctions.

PMID- 18818364
TI  - Conservation and rewiring of functional modules revealed by an epistasis map in
      fission yeast.
AB  - An epistasis map (E-MAP) was constructed in the fission yeast,
      Schizosaccharomyces pombe, by systematically measuring the phenotypes associated
      with pairs of mutations. This high-density, quantitative genetic interaction map
      focused on various aspects of chromosome function, including transcription
      regulation and DNA repair/replication. The E-MAP uncovered a previously
      unidentified component of the RNA interference (RNAi) machinery (rsh1) and linked
      the RNAi pathway to several other biological processes. Comparison of the S.
      pombe E-MAP to an analogous genetic map from the budding yeast revealed that,
      whereas negative interactions were conserved between genes involved in similar
      biological processes, positive interactions and overall genetic profiles between
      pairs of genes coding for physically associated proteins were even more
      conserved. Hence, conservation occurs at the level of the functional module
      (protein complex), but the genetic cross talk between modules can differ
      substantially.

PMID- 18818366
TI  - Complete characterization of quantum-optical processes.
AB  - The technologies of quantum information and quantum control are rapidly
      improving, but full exploitation of their capabilities requires complete
      characterization and assessment of processes that occur within quantum devices.
      We present a method for characterizing, with arbitrarily high accuracy, any
      quantum optical process. Our protocol recovers complete knowledge of the process
      by studying, via homodyne tomography, its effect on a set of coherent states,
      that is, classical fields produced by common laser sources. We demonstrate the
      capability of our protocol by evaluating and experimentally verifying the effect
      of a test process on squeezed vacuum.

PMID- 18818365
TI  - Induced pluripotent stem cells generated without viral integration.
AB  - Pluripotent stem cells have been generated from mouse and human somatic cells by
      viral expression of the transcription factors Oct4, Sox2, Klf4, and c-Myc. A
      major limitation of this technology is the use of potentially harmful genome
      integrating viruses. We generated mouse induced pluripotent stem (iPS) cells from
      fibroblasts and liver cells by using nonintegrating adenoviruses transiently
      expressing Oct4, Sox2, Klf4, and c-Myc. These adenoviral iPS (adeno-iPS) cells
      show DNA demethylation characteristic of reprogrammed cells, express endogenous
      pluripotency genes, form teratomas, and contribute to multiple tissues, including
      the germ line, in chimeric mice. Our results provide strong evidence that
      insertional mutagenesis is not required for in vitro reprogramming. Adenoviral
      reprogramming may provide an improved method for generating and studying patient
      specific stem cells and for comparing embryonic stem cells and iPS cells.

PMID- 18818367
TI  - Evolution of block copolymer lithography to highly ordered square arrays.
AB  - The manufacture of smaller, faster, more efficient microelectronic components is
      a major scientific and technological challenge, driven in part by a constant need
      for smaller lithographically defined features and patterns. Traditional self
      assembling approaches based on block copolymer lithography spontaneously yield
      nanometer-sized hexagonal structures, but these features are not consistent with
      the industry-standard rectilinear coordinate system. We present a modular and
      hierarchical self-assembly strategy, combining supramolecular assembly of
      hydrogen-bonding units with controlled phase separation of diblock copolymers,
      for the generation of nanoscale square patterns. These square arrays will enable
      simplified addressability and circuit interconnection in integrated circuit
      manufacturing and nanotechnology.

PMID- 18818368
TI  - One size fits all partnerships? What explains community partnership leadership
      skills?
AB  - The authors evaluated W. K. Kellogg-funded Community Partnerships (CPs) between
      academic, health service, and community partners in South Africa. Stakeholders (N
      = 668 respondents) completed questionnaires to explore the operational,
      functional and organisational factors that contribute to members' perceptions of
      the skills of their CPs' leadership. Ten factors accounted for 53% of leadership
      skills across five participating CPs and six stakeholder groups. Each CP
      displayed its unique footprint of factors that accounted for its leadership
      levels. Similarly, each stakeholder group had its unique signature of factors
      that were associated with its leadership. Two factors (communication mechanisms
      and operational understanding) accounted for more than 25% of leadership skills;
      management capabilities and participation benefits accounted for 4% and 3%; and
      effectiveness, benefits to difficulties ratio of being a member, engagement in
      education, flow of information and sense of ownership accounted for 2% to 3%
      each. Attention to these and other factors is warranted.

PMID- 18818369
TI  - Peptidyl-CCA deacylation on the ribosome promoted by induced fit and the O3'
      hydroxyl group of A76 of the unacylated A-site tRNA.
AB  - The last step in ribosome-catalyzed protein synthesis is the hydrolytic release
      of the newly formed polypeptide from the P-site bound tRNA. Hydrolysis of the
      ester link of the peptidyl-tRNA is stimulated normally by the binding of release
      factors (RFs). However, an unacylated tRNA or just CCA binding to the ribosomal A
      site can also stimulate deacylation under some nonphysiological conditions.
      Although the sequence of events is well described by biochemical studies, the
      structural basis of the mechanism underlying this process is not well understood.
      Two new structures of the large ribosomal subunit of Haloarcula marismortui
      complexed with a peptidyl-tRNA analog in the P site and two oligonucleotide
      mimics of unacylated tRNA, CCA and CA, in the A site show that the binding of
      either CA or CCA induces a very similar conformational change in the peptidyl
      transferase center as induced by aminoacyl-CCA. However, only CCA positions a
      water molecule appropriately to attack the carbonyl carbon of the peptidyl-tRNA
      and stabilizes the proper orientation of the ester link for hydrolysis. We, thus,
      conclude that both the ability of the O3'-hydroxyl group of the A-site A76 to
      position the water and the A-site CCA induced conformational change of the PTC
      are critical for the catalysis of the deacylation of the peptidyl-tRNA by CCA,
      and perhaps, an analogous mechanism is used by RFs.

PMID- 18818370
TI  - Transcriptional enhancement by GATA1-occupied DNA segments is strongly associated
      with evolutionary constraint on the binding site motif.
AB  - Tissue development and function are exquisitely dependent on proper regulation of
      gene expression, but it remains controversial whether the genomic signals
      controlling this process are subject to strong selective constraint. While some
      studies show that highly constrained noncoding regions act to enhance
      transcription, other studies show that DNA segments with biochemical signatures
      of regulatory regions, such as occupancy by a transcription factor, are seemingly
      unconstrained across mammalian evolution. To test the possible correlation of
      selective constraint with enhancer activity, we used chromatin
      immunoprecipitation as an approach unbiased by either evolutionary constraint or
      prior knowledge of regulatory activity to identify DNA segments within a 66-Mb
      region of mouse chromosome 7 that are occupied by the erythroid transcription
      factor GATA1. DNA segments bound by GATA1 were identified by hybridization to
      high-density tiling arrays, validated by quantitative PCR, and tested for gene
      regulatory activity in erythroid cells. Whereas almost all of the occupied
      segments contain canonical WGATAR binding site motifs for GATA1, in only 45% of
      the cases is the motif deeply preserved (found at the orthologous position in
      placental mammals or more distant species). However, GATA1-bound segments with
      high enhancer activity tend to be the ones with an evolutionarily preserved
      WGATAR motif, and this relationship was confirmed by a loss-of-function assay.
      Thus, GATA1 binding sites that regulate gene expression during erythroid
      maturation are under strong selective constraint, while nonconstrained binding
      may have only a limited or indirect role in regulation.

PMID- 18818371
TI  - Sequencing of natural strains of Arabidopsis thaliana with short reads.
AB  - Whole-genome hybridization studies have suggested that the nuclear genomes of
      accessions (natural strains) of Arabidopsis thaliana can differ by several
      percent of their sequence. To examine this variation, and as a first step in the
      1001 Genomes Project for this species, we produced 15- to 25-fold coverage in
      Illumina sequencing-by-synthesis (SBS) reads for the reference accession, Col-0,
      and two divergent strains, Bur-0 and Tsu-1. We aligned reads to the reference
      genome sequence to assess data quality metrics and to detect polymorphisms.
      Alignments revealed 823,325 unique single nucleotide polymorphisms (SNPs) and
      79,961 unique 1- to 3-bp indels in the divergent accessions at a specificity of
      >99%, and over 2000 potential errors in the reference genome sequence. We also
      identified >3.4 Mb of the Bur-0 and Tsu-1 genomes as being either extremely
      dissimilar, deleted, or duplicated relative to the reference genome. To obtain
      sequences for these regions, we incorporated the Velvet assembler into a targeted
      de novo assembly method. This approach yielded 10,921 high-confidence contigs
      that were anchored to flanking sequences and harbored indels as large as 641 bp.
      Our methods are broadly applicable for polymorphism discovery in moderate to
      large genomes even at highly diverged loci, and we established by subsampling the
      Illumina SBS coverage depth required to inform a broad range of functional and
      evolutionary studies. Our pipeline for aligning reads and predicting SNPs and
      indels, SHORE, is available for download at http://1001genomes.org.

PMID- 18818372
TI  - Review of the activation of TGF-beta in immunity.
AB  - The evolutionarily conserved TGF-beta proteins are distributed ubiquitously
      throughout the body and have a role in almost every biological process. In
      immunity, TGF-beta has an important role in modulating immunity. Much is
      understood about the process of TGF-beta production as a latent molecule and of
      the consequences and the intercellular signaling of active TGF-beta binding to
      its receptors; however, there is little discussed between the production and
      activation of TGF-beta. This review focuses on what is understood about the
      biochemical and physiological processes of TGF-beta activation and identifies the
      gaps in understanding immune cell activation of TGF-beta. A mechanistic
      understanding of the process activating TGF-beta can lead to regulating multiple
      biological systems by enhancing or inhibiting TGF-beta activation.

PMID- 18818373
TI  - Modulation of dendritic cell function by persistent viruses.
AB  - Worldwide, chronic viral infections cause major health problems with severe
      morbidity and mortality. HIV and hepatitis C virus (HCV) manifest themselves as
      persistent infections, but they are entirely distinct viruses with distinct
      replication mechanisms, tropism, and kinetics. Coinfections with HCV among people
      with HIV are emerging as a growing problem. Cellular immune responses play an
      important role in viral clearance and disease pathogenesis. However, cellular
      immunity to HIV and HCV is affected severely in chronic patients. Various
      hypotheses have been proposed to explain the dysfunctional T cell response,
      including viral escape mutations, exhaustion of the T cell compartment, and the
      activity of regulatory T cells. Also, modulation of the function of dendritic
      cells (DC) has been suggested as one of the mechanisms used by persistent viruses
      to evade the immune system. In this review, we will focus on DC interactions with
      one murine persistent virus (lymphocytic choriomeningitis virus clone 13) and two
      human persistent viruses (HIV-1 and HCV), intending to examine if general
      strategies are used by persistent viruses to modulate the function of DC to
      improve our understanding of the mechanisms underlying the development and
      maintenance of viral persistence.

PMID- 18818374
TI  - The extracellular matrix protein mindin regulates trafficking of murine
      eosinophils into the airspace.
AB  - Asthma remains a major cause of morbidity and hospitalizations in developed
      nations. Despite the widespread prevalence of this disease, the genetic and
      environmental factors that mediate development and progression of allergic
      airways disease remain poorly understood. Pulmonary recruitment of eosinophils is
      believed to contribute to many cardinal features of allergic airways disease.
      Therefore, it is paramount to understand host factors that contribute to
      pulmonary eosinophil recruitment into the lungs. Mindin is a component of
      pulmonary extracellular matrix, which can regulate inflammatory cell recruitment.
      We characterized the role of mindin in the severity of allergic airways disease
      using established murine models. There were no baseline differences in wild-type
      and mindin-deficient animals in cell counts or airway physiology. Using the OVA
      murine model of allergic airways disease, we observed that mindin-deficient
      animals have less-severe allergic airways disease with fewer airspace eosinophils
      and lower lung-lavage levels of inflammatory Th2 cytokines such as IL-13 and IL
      4. Furthermore, mindin-deficient animals have reduced airway hyper-responsiveness
      after methacholine challenge. To determine the role of mindin in eosinophil
      trafficking, independent of antigen immunization or T lymphocyte activation, we
      instilled IL-13 directly into the lungs of mice. In this model, mindin regulates
      eosinophil recruitment into the airspace. In vitro experiments demonstrate that
      mindin can enhance eotaxin-mediated eosinophil adhesion and migration, which are
      dependent on the expression of integrins alphaMbeta2 and alpha4beta1. In
      conclusion, these data suggest that mindin participates in integrin-dependent
      trafficking of eosinophils and can contribute to the severity of allergic airways
      disease.

PMID- 18818375
TI  - Hypertension increases contractile responses to hydrogen peroxide in resistance
      arteries through increased thromboxane A2, Ca2+, and superoxide anion levels.
AB  - This study investigated the mechanisms underlying the response to hydrogen
      peroxide (H(2)O(2)) in mesenteric resistance arteries from spontaneously
      hypertensive rats (SHRs) and normotensive Wistar Kyoto (WKY) rats. Arteries were
      mounted in microvascular myographs for isometric tension recording and for
      simultaneous measurements of intracellular Ca(2+) concentration ([Ca(2+)](i)),
      superoxide anion (O(2)(.)) production was evaluated by dihydroethidium
      fluorescence and confocal microscopy, and thromboxane A(2) (TXA(2)) production
      was evaluated by enzyme immunoassay. H(2)O(2) (1-100 microM) induced biphasic
      responses characterized by a transient endothelium-dependent contraction followed
      by relaxation. Simultaneous measurements of tension and Ca(2+) showed a greater
      effect of H(2)O(2) in arteries from hypertensive than normotensive rats. The
      cyclooxygenase (cox) inhibitor, indomethacin [1-(4-chlorobenzoyl)-5-methoxy-2
      methyl-1-H-indole-3-acetic acid] (1 microM); the COX-1 inhibitor, SC-58560 [5-(4
      chlorophenyl)-1-(4-methoxyphenyl)-3-trifluoromethyl pyrazole] (1 microM); the
      thromboxane (TXA(2)) synthase inhibitor, furegrelate [5-(3-pyridinylmethyl)-2
      benzofurancarboxylic acid, sodium salt] (10 microM); and the TXA(2)/prostaglandin
      H(2) receptor antagonist, SQ 29,548 ([1S
      [1.alpha.,2.alpha.(Z),3.alpha.,4.alpha.]]-7-[3-[[2-[(phenylamino) carbonyl]
      hydrazino] methyl]-7-oxabicyclo[2.2.1]hept-2-yl]-5-heptenoic acid)) (1 microM)
      abolished H(2)O(2) contraction in arteries from WKY rats but only reduced it in
      SHRs. The O(2)(.) scavenger, tiron (4,5-dihydroxy-1,3-benzenedisulfonic acid
      disodium salt) (1 mM), and the NADPH oxidase inhibitor, apocynin (4'-hydroxy-3'
      methoxyacetophenone) (0.3 mM), decreased H(2)O(2) contraction in arteries from
      SHRs but not in WKY rats. H(2)O(2) induced TXA(2) and O(2)(.) production that was
      greater in SHRs than in WKY rats. The TXA(2) analog, U46619 [9,11-di-deoxy-11
      alpha,9 alpha-epoxymethano prostaglandin F(2 alpha) (0.1 nM-1 microM)], also
      increased O(2)(.) production in SHR vessels. H(2)O(2)-induced TXA(2) production
      was decreased by SC-58560. H(2)O(2)-induced O(2)(.) production was decreased by
      tiron, apocynin, and SQ 29,548. In conclusion, the enhanced H(2)O(2) contraction
      in resistance arteries from SHRs seems to be mediated by increased TXA(2) release
      from COX-1 followed by elevations in vascular smooth muscle [Ca(2+)](i) levels
      and O(2)(.) production. This reveals a new mechanism of oxidative stress-induced
      vascular damage in hypertension.

PMID- 18818376
TI  - Sall1, sall2, and sall4 are required for neural tube closure in mice.
AB  - Four homologs to the Drosophila homeotic gene spalt (sal) exist in both humans
      and mice (SALL1 to SALL4/Sall1 to Sall4, respectively). Mutations in both SALL1
      and SALL4 result in the autosomal-dominant developmental disorders Townes-Brocks
      and Okihiro syndrome, respectively. In contrast, no human diseases have been
      associated with SALL2 to date, and Sall2-deficient mice have shown no apparent
      abnormal phenotype. We generated mice deficient in Sall2 and, contrary to
      previous reports, 11% of our Sall2-deficient mice showed background-specific
      neural tube defects, suggesting that Sall2 has a role in neurogenesis. To
      investigate whether Sall4 may compensate for the absence of Sall2, we generated
      compound Sall2 knockout/Sall4 genetrap mutant mice. In these mutants, the
      incidence of neural tube defects was significantly increased. Furthermore, we
      found a similar phenotype in compound Sall1/4 mutant mice, and in vitro studies
      showed that SALL1, SALL2, and SALL4 all co-localized in the nucleus. We therefore
      suggest a fundamental and redundant function of the Sall proteins in murine
      neurulation, with the heterozygous loss of a particular SALL protein also
      possibly compensated in humans during development.

PMID- 18818377
TI  - Foxp3+ T-regulatory cells in Sjogren's syndrome: correlation with the grade of
      the autoimmune lesion and certain adverse prognostic factors.
AB  - Sjogren's syndrome (SS) is a chronic autoimmune exocrinopathy associated with
      variable lymphocytic infiltration of the affected organs (primarily salivary and
      lacrimal glands) and broad clinical manifestations, including lymphoma
      development. To investigate the potential implication of Foxp3(+) T-regulatory
      cells in the regulation of SS inflammatory responses, we studied their incidence
      in the minor salivary glands (MSGs) and their relationship with histopathological
      and clinical disease parameters. Similar percentages of infiltrating Foxp3(+)
      cells were observed in the MSG lesions of all SS patients (n = 30) and non-SS
      sialadenitis controls (n = 7). Foxp3(+) cells were not detected in sicca
      complaining controls with negative biopsy (n = 6). In SS patients, Foxp3(+) cell
      frequency varied according to lesion severity, with the highest and lowest
      frequencies obtained in intermediate and mild MSG lesions, respectively. In the
      peripheral blood of these patients, reverse distribution of Foxp3(+) cells was
      observed. Furthermore, the frequency of Foxp3(+) cells in the MSG lesions and
      peripheral blood was negatively associated (r = -0.6679, P = 0.0065). MSG
      infiltrating Foxp3(+) cells were found to positively correlate with biopsy focus
      score (P = 0.05), infiltrating mononuclear cells, dendritic cells, and
      macrophages (P </= 0.024 each), and serum C4 levels (P = 0.0328), whereas lower
      Foxp3(+) cell incidence correlated with adverse predictors for lymphoma
      development, such as the presence of C4 hypocomplementemia (P = 0.012) and SG
      enlargement (tendency, P = 0.067). Our findings suggest that the Foxp3(+) T
      regulatory cell frequency in the MSG lesions of SS patients correlates with
      inflammation grade and certain risk factors for lymphoma development.

PMID- 18818378
TI  - Hyaluronan-mediated leukocyte adhesion and dextran sulfate sodium-induced colitis
      are attenuated in the absence of signal transducer and activator of transcription
      1.
AB  - Inflammatory bowel disease is a chronic inflammatory condition of the intestinal
      mucosa whose etiology is unclear but is likely to be multifactorial. We have
      shown previously that an increased amount of hyaluronan (HA) is present both in
      the inflamed mucosa of inflammatory bowel disease patients and in isolated human
      cells after polyI:C treatment. The signal transducer and activator of
      transcription (STAT)1 protein plays an important role in many signaling pathways
      that are associated with inflammation. We therefore investigated the role of
      STAT1 in adhesive interactions that occur between leukocytes and polyI:C-induced
      mucosal smooth muscle cells (M-SMCs). Activation of STAT1 was observed after the
      polyI:C treatment of M-SMCs. Specific phosphorylation of tyrosine and serine
      residues of STAT1 was observed in polyI:C-treated, but not untreated, M-SMC
      cultures. To evaluate further the role of STAT1, a corresponding STAT-1-null
      mouse was used. PolyI:C-induced, HA-mediated leukocyte adhesion to colon SMCs
      from STAT1-null mice was significantly decreased compared with that from wild
      type control mice. In vivo, using the dextran sulfate sodium-induced model of
      colon inflammation, both tissue damage and HA deposition were attenuated in STAT1
      null mice compared with that in wild-type control mice. Additionally, the inter
      alpha-trypsin inhibitor (IalphaI), a proteoglycan essential for facilitating
      leukocyte binding to the HA matrix, was reduced in STAT1-null mice. Together,
      these results demonstrate that STAT1 plays an important role in HA-mediated
      inflammatory processes.

PMID- 18818379
TI  - Caspase-3 is enriched in postsynaptic densities and increased in Alzheimer's
      disease.
AB  - Progressive synaptic degeneration and neuron loss are major structural correlates
      of cognitive impairment in Alzheimer's disease (AD). The mechanisms by which
      synaptic degeneration in AD occurs have not been established. The activation of
      proteins within the caspase family has been implicated in AD-associated
      neurodegeneration, and synaptically localized caspase activity could play a role
      in the synaptic degeneration and loss found in AD. We used synaptosomal
      fractionation with Western blotting and immunohistochemistry to examine the
      anatomical, subcellular, and subsynaptic expression patterns of caspase 3 in both
      the anterior cingulate cortex and hippocampus of control and AD patients. In both
      control and AD cases, there was a selective enrichment of caspase- 3 at synapses,
      particularly in the postsynaptic density (PSD) fractions. Compared with controls,
      AD patients exhibited significant increases in synaptic procaspase- 3 and active
      caspase-3 expression levels that were most evident in the PSD fractions. These
      data demonstrate for the first time the preferential localization and increase of
      caspase-3 in the PSD fractions in AD and suggest an important role for caspase 3
      in synapse degeneration during disease progression.

PMID- 18818380
TI  - Involvement of the lysophosphatidic acid-generating enzyme autotaxin in
      lymphocyte-endothelial cell interactions.
AB  - Autotaxin (ATX) is a secreted protein with lysophospholipase D activity that
      generates lysophosphatidic acid (LPA) from lysophosphatidylcholine. Here we
      report that functional ATX is selectively expressed in high endothelial venules
      (HEVs) of both lymph nodes and Peyer's patches. ATX expression was
      developmentally regulated and coincided with lymphocyte recruitment to the lymph
      nodes. In adults, ATX expression was independent of HEV-expressed chemokines such
      as CCL21 and CXCL13, innate immunity signals including those via TLR4 or MyD88,
      and of the extent of lymphocyte trafficking across the HEVs. ATX expression was
      induced in venules at sites of chronic inflammation. Receptors for the ATX enzyme
      product LPA were constitutively expressed in HEV endothelial cells (ECs). In
      vitro, LPA induced strong morphological changes in HEV ECs. Forced ATX expression
      caused cultured ECs to respond to lysophosphatidylcholine, up-regulating
      lymphocyte binding to the ECs in a LPA receptor-dependent manner under both
      static and flow conditions. Although in vivo depletion of circulating ATX did not
      affect lymphocyte trafficking into the lymph nodes, we surmise, based on the
      above data, that ATX expressed by HEVs acts on HEVs in situ to facilitate
      lymphocyte binding to ECs and that ATX in the general circulation does not play a
      major role in this process. Tissue-specific inactivation of ATX will verify this
      hypothesis in future studies of its mechanism of action.

PMID- 18818382
TI  - Effects of hyperbaric gases on membrane nanostructure and function in neurons.
AB  - This mini-review summarizes current ideas of how hyperbaric gases (>1-10
      atmospheres absolute) affect neuronal mechanisms of excitability through
      molecular interaction with membrane components. The dynamic nature of the lipid
      bilayer, its resident proteins, and the underlying cytoskeleton make each
      respective nanostructure a potential target for modulation by hyperbaric gases.
      Depending on the composition of the gas mixture, the relative concentrations of
      O(2) and inert gas, and total barometric pressure, the net effect of a particular
      gas on the cell membrane will be determined by the gas' 1) lipid solubility, 2)
      ability to oxidize lipids and proteins (O(2)), and 3) capacity, in the compressed
      state, to generate localized shear and strain forces between various
      nanostructures. A change in the properties of any one membrane component is
      anticipated to change conductance of membrane-spanning ion channels and thus
      neuronal function.

PMID- 18818381
TI  - Enhanced integrated stress response promotes myelinating oligodendrocyte survival
      in response to interferon-gamma.
AB  - The T-cell-derived, pleiotropic cytokine interferon (IFN)-gamma is believed to
      play a key regulatory role in immune-mediated demyelinating disorders of the
      central nervous system, including multiple sclerosis and experimental autoimmune
      encephalomyelitis. Our previous work has demonstrated that the endoplasmic
      reticulum (ER) stress response modulates the response of oligodendrocytes to this
      cytokine. The ER stress response activates the pancreatic ER kinase, which
      coordinates an adaptive program known as the integrated stress response by
      phosphorylating translation initiation factor 2alpha (eIF2alpha). In this study,
      we found that growth arrest and DNA damage 34 (GADD34), a stress-inducible
      regulatory subunit of a phosphatase complex that dephosphorylates eIF2alpha, was
      selectively up-regulated in myelinating oligodendrocytes in mice that ectopically
      expressed IFN-gamma in the central nervous system. We also found that a GADD34
      mutant strain of mice displayed increased levels of phosphorylated eIF2alpha (p
      eIF2alpha) in myelinating oligodendrocytes when exposure to IFN-gamma, as well as
      diminished oligodendrocyte loss and hypomyelination. Furthermore, treatment with
      salubrinal, a small chemical compound that specifically inhibits protein
      phosphatase 1(PP1)-GADD34 phosphatase activity, increased the levels of p
      eIF2alpha and ameliorated hypomyelination and oligodendrocyte loss in cultured
      hippocampal slices exposed to IFN-gamma. Thus, our data provide evidence that an
      enhanced integrated stress response could promote oligodendrocyte survival in
      immune-mediated demyelination diseases.

PMID- 18818383
TI  - Contraction-stimulated glucose transport in rat skeletal muscle is sustained
      despite reversal of increased PAS-phosphorylation of AS160 and TBC1D1.
AB  - Akt substrate of 160 kDa (AS160), the most distal insulin signaling protein known
      to be important for insulin-stimulated glucose transport, becomes phosphorylated
      with skeletal muscle contraction. Akt, AMP-activated protein kinase (AMPK), and
      Ca(2+)/calmodulin-dependent kinase II (CaMKII) have been implicated in regulating
      AS160 and/or glucose transport. Our primary aim was to assess time courses for
      contraction's effects on glucose transport and phosphorylation of Akt, AMPK,
      CaMKII, and AS160. Isolated rat epitrochlearis muscles were studied without or
      with contraction (5, 10, 20, 40, 60 min). Phospho-Akt substrate (PAS) antibody
      was used to measure AS160 PAS phosphorylation by quantifying the approximately
      160-kDa band on PAS immunoblots (PAS-160); a separate band at 150 kDa (PAS-150)
      that responded similarly to contraction was also identified. Using specific
      antibodies for AS160 or TBC1D1 on immunoblots, the molecular mass of PAS-160 was
      found to correspond with that of AS160 and not TBC1D1, whereas PAS-150
      corresponded with TBC1D1 and not AS160. Furthermore, supernatant of sample
      immunodepleted with anti-AS160 had greatly reduced PAS-160, whereas supernatant
      of sample immunodepleted with anti-TBC1D1 had greatly reduced PAS-150, providing
      further evidence that PAS-160 and PAS-150 correspond with PAS-AS160 and PAS
      TBC1D1, respectively. Contraction induced transient increases in PAS-160, PAS
      150, phospho-glycogen synthase kinase 3 (an Akt substrate) and phospho-CaMKII;
      glucose transport and phospho-AMPK increases were maintained for 60 min of
      contraction. These data suggest the following: 1) PAS-160 (AS160) and PAS-150
      (TBC1D1) respond to contraction transiently, despite sustained stimulation; 2)
      continual AMPK activation was insufficient for sustained increase in PAS-160 or
      PAS-150; and 3) sustained elevation of PAS-160 or PAS-150 was unnecessary to
      maintain contraction-stimulated glucose transport for up to 60 min.

PMID- 18818384
TI  - Contribution of upper airway geometry to convective mixing.
AB  - We investigated the axial dispersive effect of the upper airway structure
      (comprising mouth cavity, oropharynx, and trachea) on a traversing aerosol bolus.
      This was done by means of aerosol bolus experiments on a hollow cast of a
      realistic upper airway model (UAM) and three-dimensional computational fluid
      dynamics (CFD) simulations in the same UAM geometry. The experiments showed that
      50-ml boluses injected into the UAM dispersed to boluses with a half-width
      ranging from 80 to 90 ml at the UAM exit, across both flow rates (250, 500 ml/s)
      and both flow directions (inspiration, expiration). These experimental results
      imply that the net half-width induced by the UAM typically was 69 ml. Comparison
      of experimental bolus traces with a one-dimensional Gaussian-derived analytical
      solution resulted in an axial dispersion coefficient of 200-250 cm(2)/s,
      depending on whether the bolus peak and its half-width or the bolus tail needed
      to be fully accounted for. CFD simulations agreed well with experimental results
      for inspiratory boluses and were compatible with an axial dispersion of 200
      cm(2)/s. However, for expiratory boluses the CFD simulations showed a very tight
      bolus peak followed by an elongated tail, in sharp contrast to the expiratory
      bolus experiments. This indicates that CFD methods that are widely used to
      predict the fate of aerosols in the human upper airway, where flow is
      transitional, need to be critically assessed, possibly via aerosol bolus
      simulations. We conclude that, with all its geometric complexity, the upper
      airway introduces a relatively mild dispersion on a traversing aerosol bolus for
      normal breathing flow rates in inspiratory and expiratory flow directions.

PMID- 18818385
TI  - Intermittent hypoxia activates peptidylglycine alpha-amidating monooxygenase in
      rat brain stem via reactive oxygen species-mediated proteolytic processing.
AB  - Intermittent hypoxia (IH) associated with sleep apneas leads to cardiorespiratory
      abnormalities that may involve altered neuropeptide signaling. The effects of IH
      on neuropeptide synthesis have not been investigated. Peptidylglycine alpha
      amidating monooxygenase (PAM; EC 1.14.17.3) catalyzes the alpha-amidation of
      neuropeptides, which confers biological activity to a large number of
      neuropeptides. PAM consists of O(2)-sensitive peptidylglycine alpha-hydroxylating
      monooxygenase (PHM) and peptidyl-alpha-hydroxyglycine alpha-amidating lyase (PAL)
      activities. Here, we examined whether IH alters neuropeptide synthesis by
      affecting PAM activity and, if so, by what mechanisms. Experiments were performed
      on the brain stem of adult male rats exposed to IH (5% O(2) for 15 s followed by
      21% O(2) for 5 min; 8 h/day for up to 10 days) or continuous hypoxia (0.4 atm for
      10 days). Analysis of brain stem extracts showed that IH, but not continuous
      hypoxia, increased PHM, but not PAL, activity of PAM and that the increase of PHM
      activity was associated with a concomitant elevation in the levels of alpha
      amidated forms of substance P and neuropeptide Y. IH increased the relative
      abundance of 42- and 35-kDa forms of PHM ( approximately 1.6- and 2.7-fold,
      respectively), suggesting enhanced proteolytic processing of PHM, which appears
      to be mediated by an IH-induced increase of endoprotease activity. Kinetic
      analysis showed that IH increases V(max) but has no effect on K(m). IH increased
      generation of reactive oxygen species in the brain stem, and systemic
      administration of antioxidant prevented IH-evoked increases of PHM activity,
      proteolytic processing of PHM, endoprotease activity, and elevations in substance
      P and neuropeptide Y amide levels. Taken together, these results demonstrate that
      IH activates PHM in rat brain stem via reactive oxygen species-dependent
      posttranslational proteolytic processing and further suggest that PAM activation
      may contribute to IH-mediated peptidergic neurotransmission in rat brain stem.

PMID- 18818386
TI  - Effects of physical activity on strength and skeletal muscle fat infiltration in
      older adults: a randomized controlled trial.
AB  - Considerable evidence suggests that the loss of strength and muscle mass appear
      to be inevitable consequences of aging. Moreover, aging is associated with an
      increase in body fat. This study examined whether increased physical activity
      could prevent or reverse the losses of strength and skeletal muscle mass as well
      as the gain in fat in older adults. Eleven men and 31 women completed a
      randomized trial consisting of either a physical activity (PA; n = 22) or
      successful aging health educational control (SA; n = 20) group. Isokinetic knee
      extensor strength and computed tomography-derived midthigh skeletal muscle and
      adipose tissue cross-sectional areas (CSA) were assessed at baseline and at 12 mo
      following randomization. Total body weight and muscle CSA decreased in both
      groups, but these losses were not different between groups. Strength adjusted for
      muscle mass decreased (-20.1 +/- 9.3%, P < 0.05) in SA. The loss of strength was
      completely prevented in PA (+2.5 +/- 8.3%). In addition, there was a significant
      increase (18.4 +/- 6.0%) in muscle fat infiltration in SA, but this gain was
      nearly completely prevented in PA (2.3 +/- 5.7%). In conclusion, regular physical
      activity prevents both the age-associated loss of muscle strength and increase in
      muscle fat infiltration in older adults with moderate functional limitations.

PMID- 18818387
TI  - Head-down tilt posture elicits transient lymphocyte mobilization from the iliac,
      but not mesenteric, lymph nodes of rats.
AB  - The effects of short-term simulated microgravity on the lymph dynamics of rat
      lymph nodes were investigated using a combination of Bollman's cage and head-down
      tilt (HDT). Efferent lymphatics of the iliac and mesenteric lymph nodes were
      cannulated for the collection of lymph. There was no significant difference in
      lymph flow rate from the iliac lymph nodes between non-HDT (control) and HDT
      rats. Lymph flow rate from the mesenteric lymph nodes in HDT rats was slightly
      higher than that obtained with the control. The cell count obtained from the
      iliac lymph nodes in HDT rats was significantly larger than those of the
      controls, while no significant difference in the number of cells from the
      mesenteric lymph nodes was observed between the control and HDT groups. The cells
      from the iliac lymph nodes in the control and HDT rats were mostly lymphocytes.
      The distribution of subsets of lymphocytes (CD3+, CD4+, CD8a+, and CD45R+) from
      the iliac lymph nodes in HDT rats was not significantly different from the
      subsets of lymphocytes in the control. Immunization did not affect the
      distribution of lymphocyte subsets from the iliac lymph nodes in the control and
      HDT groups. There was no significant difference in the concentrations of lymph
      albumin in iliac afferent or efferent lymphatics between the control and HDT
      groups. These findings suggest that HDT posture in Bollman's cage induces
      transient output of lymphocytes from the iliac lymph nodes of rats in vivo
      without changing the flow rate, lymphocyte subsets, or concentration of albumin.

PMID- 18818389
TI  - Stimulation of dendritic cells via the dectin-1/Syk pathway allows priming of
      cytotoxic T-cell responses.
AB  - The C-type lectin receptor dectin-1 functions as a pattern recognition receptor
      for beta-glucans and signals via Syk kinase but independently of the Toll-like
      receptor (TLR) pathway to regulate expression of innate response genes. Dectin-1
      signaling can promote activation of dendritic cells (DCs), rendering them
      competent to prime Th1 and Th17 responses. Here we show that dectin-1-activated
      DCs can also prime cytotoxic T-lymphocyte (CTL) responses. DCs exposed to a
      dectin-1 agonist induced antigen-specific expansion of TCR transgenic CD8(+) T
      cells and their differentiation into CTLs in vitro. Dectin-1 agonist also acted
      as an adjuvant for CTL crosspriming in vivo, eliciting potent CTL responses that
      protected mice from tumor challenge. In vitro but not in vivo, CTL crosspriming
      was dependent on IL-12 p70, which was produced by dectin-1-activated DCs in
      response to IFN-gamma secreted by newly activated CD8(+) T cells. The dectin
      1/Syk pathway is thus able to couple innate immune recognition of beta-glucans to
      all branches of the adaptive immune system, including CD4(+) T-helper cells, B
      cells, and CD8(+) cytotoxic T cells. These data highlight the ability of non-TLR
      receptors to bridge innate and adaptive immunity and suggest that dectin-1
      agonists may constitute useful adjuvants for immunotherapy and vaccination.

PMID- 18818388
TI  - MLL5 contributes to hematopoietic stem cell fitness and homeostasis.
AB  - MLL5 is a novel trithorax group gene and a candidate tumor suppressor gene
      located within a 2.5-Mb interval of chromosome band 7q22 that frequently is
      deleted in human myeloid malignancy. Here we show that inactivation of the Mll5
      gene in mice results in a 30% reduction in the average representation of
      hematopoietic stem cells and in functional impairment of long-term hematopoietic
      repopulation potential under competitive conditions. Bone marrow cells from Mll5
      deficient mice were defective in spleen colony-forming assays, and the mutant
      mice showed enhanced susceptibility to 5-fluorouracil-induced myelosuppression.
      Heterozygous and homozygous Mll5 mutant mice did not spontaneously develop
      hematologic cancers, and loss of Mll5 did not alter the phenotype of a fatal
      myeloproliferative disorder induced by oncogenic Kras in vivo. Collectively, the
      data reveal an important role for Mll5 in HSC homeostasis and provide a basis for
      further studies to explore its role in leukemogenesis.

PMID- 18818390
TI  - An L-selectin ligand distinct from P-selectin glycoprotein ligand-1 is expressed
      on endothelial cells and promotes neutrophil rolling in inflammation.
AB  - Neutrophils recruited from the blood are key players in the innate immune
      response. Selectins play critical roles in neutrophil recruitment by mediating
      their tethering and rolling in inflamed venules. While the roles of P- and E
      selectin in this process are well established, the mechanisms of L-selectin
      mediated neutrophil recruitment remain elusive. One proposal is that tethering is
      mediated by L-selectin on flowing neutrophils interacting with P-selectin
      glycoprotein ligand-1 (PSGL-1) on adherent neutrophils. To clarify whether L
      selectin-mediated neutrophil recruitment depends entirely on PSGL-1, we examined
      the impact of L-selectin deficiency in mice with a PSGL-1-deficient background. L
      selectin and PSGL-1 double-knockout mice exhibited a higher increase in their
      peripheral blood neutrophil count and a worse defect in neutrophil recruitment
      into the inflamed peritoneum than PSGL-1-deficient mice. Intravital microscopy of
      inflamed cremaster muscle venules showed that L-selectindeficiency or antibody
      blockade of L-selectin reduced the residual leukocyte rolling in PSGL-1-deficient
      mice. Flow cytometric analyses showed that the endothelial cells from the
      cremaster muscle bound L-selectin in a PSGL-1-independent manner. These results
      provide evidence for the existence of an L-selectin ligand distinct from PSGL-1
      in inflammation and indicate that such a ligand is expressed on endothelial
      cells, promoting neutrophil rolling in vivo.

PMID- 18818391
TI  - Characteristics and outcome of chronic myeloid leukemia patients with F317L BCR
      ABL kinase domain mutation after therapy with tyrosine kinase inhibitors.
AB  - Mutations in codon 317 after treatment with imatinib and dasatinib have been
      reported. We reviewed patients with chronic myeloid leukemia and mutations after
      tyrosine kinase inhibitor (TKI) therapy. F317L was detected in 20, including
      12/99 (12%) with mutation after imatinib failure, and 8/16 (50%) after dasatinib
      (P = .001). Median follow-up from mutation detection was 25 months. At the time
      of F317L, 8 patients were in chronic phase (CP), 6 in accelerated phase, and 6 in
      blast phase. There was no difference in characteristics between patients with or
      without F317L mutations, or with no mutations. A complete cytogenetic response
      was achieved in 3 of 6 patients treated with nilotinib, 2 of 2 with imatinib, and
      0 of 3 with dasatinib. Survival of patients with F317L was similar to those with
      other mutations (P = .45). Patients in CP had better outcome, with a 2-year
      survival of 75%. F317L mutation is resistant to dasatinib but sensitive to other
      TKIs. The prognosis is dependent mostly on the disease stage.

PMID- 18818392
TI  - Defective Notch activation in microenvironment leads to myeloproliferative
      disease.
AB  - Despite the great importance of nonhematopoietic cells constituting the
      microenvironment for normal hematopoiesis, the cellular interactions between
      nonhematopoietic cells themselves are largely unknown. Using the Cre-loxP system
      in mice to inactivate Mind bomb-1 (Mib1), an essential component for Notch ligand
      endocytosis, here we show that the development of an MPD is dependent on
      defective Notch activation in the microenvironment. Our 2 independent Mib1
      conditional knockout (CKO) mouse lines each developed a myeloproliferative
      disease (MPD), with gradual accumulations of immature granulocytes. The mutant
      mice showed hepatosplenomegaly, anemia, granulocytosis, and leukocyte
      infiltration in multiple organs and finally died at approximately 20 weeks of
      age. We were surprised to find that the transplantation of wild-type bone marrow
      cells into the Mib1-null microenvironment resulted in a de novo MPD. Moreover, by
      introducing the constitutively active intracellular domain of Notch1 in the Mib1
      null background, we show that active Notch1 expression in the Mib1-null
      microenvironment significantly suppressed the disease progression, suggesting
      that the MPD development in the Mib1 CKO mice is due to defective Notch
      activation in the nonhematopoietic cells. These findings demonstrate that normal
      hematopoiesis absolutely requires Notch activation through the Notch ligand
      receptor interaction between microenvironmental cells themselves and shed light
      on the microenvironment that fosters hematopoietic disorders.

PMID- 18818393
TI  - Imaging of plasmacytoid dendritic cell interactions with T cells.
AB  - Plasmacytoid dendritic cells (pDCs) efficiently produce type I interferon and
      participate in adaptive immune responses, although the molecular interactions
      between pDCs and antigen-specific T cells remain unknown. This study examines
      immune synapse (IS) formation between murine pDCs and CD4(+) T cells. Mature pDCs
      formed canonical ISs, involving relocation to the contact site of the microtubule
      organizing center, F-actin, protein kinase C-, and pVav, and activation of early
      signaling molecules in T cells. However, immature pDCs were less efficient at
      forming conjugates with T cells and inducing IS formation, microtubule-organizing
      center translocation, and T-cell signaling and activation. Time-lapse
      videomicroscopy and 2-photon in vivo imaging of pDC-T-cell interactions revealed
      that immature pDCs preferentially mediated transient interactions, whereas mature
      pDCs promoted more stable contacts. Our data indicate that, under steady-state
      conditions, pDCs preferentially establish transient contacts with naive T cells
      and show a very modest immunogenic capability, whereas on maturation, pDCs are
      able to form long-lived contacts with T cells and significantly enhance their
      capacity to activate these lymphocytes.

PMID- 18818394
TI  - CaMKII promotes TLR-triggered proinflammatory cytokine and type I interferon
      production by directly binding and activating TAK1 and IRF3 in macrophages.
AB  - Calcium and its major downstream effector, calcium/calmodulin-dependent protein
      kinase II (CaMKII), are found to be important for the functions of immune cells.
      Lipopolysaccharide (LPS) has been shown to induce intracellular calcium release
      in macrophages; however, whether and how CaMKII is required for Toll-like
      receptor (TLR) signaling remain unknown. Here we demonstrate that TLR 4, 9, and 3
      ligands markedly induce intracellular calcium fluxes and activate CaMKII-alpha in
      macrophages. Selective inhibition or RNA interference of CaMKII significantly
      suppresses TLR4, 9, 3-triggered production of interleukin-6 (IL-6), tumor
      necrosis factor-alpha, and interferon-alpha/beta (IFN-alpha/beta) in macrophages.
      Coincidently, overexpression of constitutively active CaMKII-alpha significantly
      enhances production of the above cytokines. In addition to the activation of
      mitogen-activated protein kinase and nuclear factor kappaB pathways, CaMKII-alpha
      can directly bind and phosphorylate transforming growth factor beta-activated
      kinase 1 (TAK1) and IFN regulatory factor 3 (IRF3; serine on 386) via the N
      terminal part of its regulatory domain. Therefore, CaMKII can be activated by TLR
      ligands, and in turn promotes both myeloid differentiating factor 88 and Toll/IL
      1 receptor domain-containing adaptor protein-inducing IFN-beta-dependent
      inflammatory responses by directly activating TAK1 and IRF3. The cross-talk with
      the calcium/CaMKII pathway is needed for full activation of TLR signaling in
      macrophages.

PMID- 18818395
TI  - The CD34-like protein PODXL and alpha6-integrin (CD49f) identify early progenitor
      MSCs with increased clonogenicity and migration to infarcted heart in mice.
AB  - We screened for surface proteins expressed only by the early progenitor cells
      present in low-passage, low-density cultures of the adult stem/progenitor cells
      from bone marrow referred to as mesenchymal stem cells or multipotent stromal
      cells (MSCs). Six proteins were identified that were selectively expressed in the
      early progenitors: podocalyxin-like protein (PODXL), alpha6-integrin (CD49f),
      alpha4-integrin (CD49d), c-Met, CXCR4, and CX3CR1. All were previously shown to
      be involved in cell trafficking or tumor progression. Antibodies to CD49f and
      PODXL, a sialomucin in the CD34 family, were the most robust for FACScan assays.
      PODXL(hi)/CD49f(hi) MSCs were more clonogenic and differentiated more efficiently
      than PODXL(lo)/CD49f(lo) cells. Inhibition of expression of PODXL with RNA
      interference caused aggregation of the cells. Furthermore, PODXL(hi)/CD49f(hi)
      MSCs were less prone to produce lethal pulmonary emboli, and larger numbers were
      recovered in heart and kidney after intravenous infusion into mice with
      myocardial infarcts.

PMID- 18818396
TI  - The c-myb proto-oncogene and microRNA-15a comprise an active autoregulatory
      feedback loop in human hematopoietic cells.
AB  - The c-myb proto-oncogene encodes an obligate hematopoietic cell transcription
      factor important for lineage commitment, proliferation, and differentiation.
      Given its critical functions, c-Myb regulatory factors are of great interest but
      remain incompletely defined. Herein we show that c-Myb expression is subject to
      posttranscriptional regulation by microRNA (miRNA)-15a. Using a luciferase
      reporter assay, we found that miR-15a directly binds the 3'-UTR of c-myb mRNA. By
      transfecting K562 myeloid leukemia cells with a miR-15a mimic, functionality of
      binding was shown. The mimic decreased c-Myb expression, and blocked the cells in
      the G(1) phase of cell cycle. Exogenous expression of c-myb mRNA lacking the 3'
      UTR partially rescued the miR-15a induced cell-cycle block. Of interest, the miR
      15a promoter contained several potential c-Myb protein binding sites. Occupancy
      of one canonical c-Myb binding site was demonstrated by chromatin
      immunoprecipitation analysis and shown to be required for miR-15a expression in
      K562 cells. Finally, in studies using normal human CD34(+) cells, we showed that
      c-Myb and miR-15a expression were inversely correlated in cells undergoing
      erythroid differentiation, and that overexpression of miR-15a blocked both
      erythroid and myeloid colony formation in vitro. In aggregate, these findings
      suggest the presence of a c-Myb-miR-15a autoregulatory feedback loop of potential
      importance in human hematopoiesis.

PMID- 18818397
TI  - Treatment of early childhood medulloblastoma by postoperative chemotherapy and
      deferred radiotherapy.
AB  - To investigate the utility of postoperative chemotherapy in delaying radiotherapy
      and to identify prognostic factors in early childhood medulloblastoma, we studied
      children younger than 3 years of age registered to the HIT-SKK'87
      (Therapieprotokoll fur Sauglinge und Kleinkinder mit Hirntumoren [Brain Tumor
      Radiotherapy for Infants and Toddlers with Medulloblastoma] 1987) trial who
      received systemic interval chemotherapy until craniospinal radiotherapy was
      applied at 3 years of age or at relapse, from 1987 to 1993. Children with
      postoperative residual tumor or metastatic disease received systemic induction
      chemotherapy prior to interval chemotherapy. Twenty-nine children were eligible
      for analyses (median age, 1.7 years; median follow-up, 12.6 years). In children
      without macroscopic metastases, rates (+/-SEM) for 10-year progression-free
      survival (PFS) and overall survival (OS) were 52.9% +/- 12.1% and 58.8% +/- 11.9%
      (complete resection), and 55.6% +/- 16.6% and 66.7% +/- 15.7% (incomplete
      resection), compared with 0% and 0% in children with macroscopic metastases.
      Survival was superior in nine children with desmoplastic or extensive nodular
      histology compared with 20 children with classic medulloblastoma (10-year PFS,
      88.9% +/- 10.5% and 30.0% +/- 10.3%, p = 0.003; OS, 88.9% +/- 10.5% and 40.0% +/-
      11.0%, p = 0.006). Eleven of 12 children with tumor progression during
      chemotherapy had classic medulloblastoma. After treatment, IQ scores were
      inferior compared with nonirradiated children from the subsequent study, HIT
      SKK'92. Classic histology, metastatic disease, and male gender were independent
      adverse risk factors for PFS and OS in 72 children from HIT-SKK'87 and HIT-SKK'92
      combined. In terms of survival, craniospinal radiotherapy was successfully
      delayed especially in young children with medulloblastoma of
      desmoplastic/extensive nodular histology, which was a strong independent
      favorable prognostic factor. Because of the neurocognitive deficits of survivors,
      the emerging concepts to avoid craniospinal radiotherapy should rely on the
      histological medulloblastoma subtype.

PMID- 18818398
TI  - Statins and nitric oxide production against ischemic stroke.

PMID- 18818399
TI  - The 2008 William M. Feinberg lecture: prioritizing stroke research.
AB  - Stroke is a tremendous burden to health worldwide both in the developed and
      developing world. Current levels of research funding do not adequately reflect
      this burden, particularly when expected increases in stroke rates are considered.
      Of course, an investment in stroke research is only justified if a return can be
      expected. The ultimate goal of stroke research is to reduce the burden of
      disease, and clinical trials are the clearest expression of the value of research
      because their results can directly impact health. In a review of stroke trials
      funded by the US National Institute of Neurological Disorders and Stroke, we
      found that the overall impact of the trials was dramatically positive and
      justified the entire research budget of the Institute. Nonetheless, there were
      obvious opportunities for improvement. METHODS: meta--research--on topics not
      just relevant to stroke, but to the study of all disease.

PMID- 18818400
TI  - Estrogen receptor alpha gene haplotypes and diplotypes in the risk of stroke.

PMID- 18818401
TI  - Recurrent stroke and massive right-to-left shunt: results from the prospective
      Spanish multicenter (CODICIA) study.
AB  - BACKGROUND AND PURPOSE: Few studies have prospectively examined the risk of
      recurrent stroke associated with patent foramen ovale. We present the results of
      the Spanish right-to-left shunt (RLSh) multicenter study. METHODS: Four hundred
      eighty-six patients with cryptogenic stoke were included at 17 participating
      hospitals. Patients were examined by contrast transcranial Doppler methods at
      baseline. The magnitude of RLSh was quantified during the Valsalva maneuver.
      Transthoracic and/or transesophageal echocardiography, computed tomography scan,
      or magnetic resonance imaging was performed. Functional outcome and stroke
      recurrence were evaluated at 3 months and yearly thereafter. The independent
      relation between RLSh magnitude and stroke recurrence was analyzed by logistic
      regression analysis in the whole group and in the younger subgroup (<55 years).
      RESULTS: Massive RLSh was detected in 200 patients (41.2%). The mean follow-up
      was 729+/-411 days. Stroke recurrence was low (5.8%, n=28) and similar in
      patients with massive RLSh, with nonmassive RLSh, and with no RLSh, in both the
      younger group (3.4% vs 2.3% vs 4.5%, respectively; P=0.75) and in the whole
      population (5.0% vs 6.2% vs 6.3%, respectively; P=0.58). Regression analysis
      found no association between massive RLSh and recurrent stroke in either group
      (in the whole population, odds ratio=0.94; 95% CI, 0.36 to 2.40; P=0.89; in the
      younger population, odds ratio=0.93; 95% CI, 0.18 to 4.91; P=0.93). These results
      were similar when concurrent atrial septal aneurysm and massive RLSh were
      analyzed and when antithrombotic treatment and concomitant stroke risk factors
      were included. CONCLUSIONS: These results suggest that neither massive RLSh nor
      massive RLSh with concurrent atrial septal aneurysm is an independent risk factor
      for recurrent stroke, in either the general or younger stroke populations.

PMID- 18818402
TI  - Determination of wall tension in cerebral artery aneurysms by numerical
      simulation.
AB  - BACKGROUND AND PURPOSE: Cerebral artery aneurysms rupture when wall tension
      exceeds the strength of the wall tissue. At present, risk-assessment of
      unruptured aneurysms does not include evaluation of the lesions shape, yet
      clinical experience suggests that this is of importance. We aimed to develop a
      computational model for simulation of fluid-structure interaction in cerebral
      aneurysms based on patient specific lesion geometry, with special emphasis on
      wall tension. METHODS: An advanced isogeometric fluid-structure analysis model
      incorporating flexible aneurysm wall based on patient specific computed
      tomography angiogram images was developed. Variables used in the simulation model
      were retrieved from a literature review. RESULTS: The simulation results exposed
      areas of high wall tension and wall displacement located where aneurysms usually
      rupture. CONCLUSIONS: We suggest that analyzing wall tension and wall
      displacement in cerebral aneurysms by numeric simulation could be developed into
      a novel method for individualized prediction of rupture risk.

PMID- 18818403
TI  - The PPARalpha/p16INK4a pathway inhibits vascular smooth muscle cell proliferation
      by repressing cell cycle-dependent telomerase activation.
AB  - Peroxisome proliferator-activated receptor (PPAR)alpha, the molecular target for
      fibrates used to treat dyslipidemia, exerts pleiotropic effects on vascular
      cells. In vascular smooth muscle cells (VSMCs), we have previously demonstrated
      that PPARalpha activation suppresses G(1)-->S cell cycle progression by targeting
      the cyclin-dependent kinase inhibitor p16(INK4a) (p16). In the present study, we
      demonstrate that this inhibition of VSMC proliferation by PPARalpha is mediated
      through a p16-dependent suppression of telomerase activity, which has been
      implicated in key cellular functions including proliferation. PPARalpha
      activation inhibited mitogen-induced telomerase activity by repressing the
      catalytic subunit telomerase reverse transcriptase (TERT) through negative cross
      talk with an E2F-1-dependent trans-activation of the TERT promoter. This trans
      repression involved the recruitment of the retinoblastoma (RB) family proteins
      p107 and p130 to the TERT promoter resulting in impaired E2F-1 binding, an effect
      that was dependent on p16. The inhibition of cell proliferation by PPARalpha
      activation was lost in VSMCs following TERT overexpression or knockdown, pointing
      to a key role of telomerase as a target for the antiproliferative effects of
      PPARalpha. Finally, we demonstrate that PPARalpha agonists suppress telomerase
      activation during the proliferative response following vascular injury,
      indicating that these findings are applicable in vivo. In concert, these results
      demonstrate that the antiproliferative effects of PPARalpha in VSMCs depend on
      the suppression of telomerase activity by targeting the p16/RB/E2F
      transcriptional cascade.

PMID- 18818404
TI  - Inducible nitric oxide synthase expression and cardiomyocyte dysfunction during
      sustained moderate ischemia in pigs.
AB  - In acute myocardial ischemia, regional blood flow and function are proportionally
      reduced. With prolongation of ischemia, function further declines at unchanged
      blood flow. We studied the involvement of an inflammatory signal cascade in such
      progressive dysfunction and whether dysfunction is intrinsic to cardiomyocytes.
      In 10 pigs, ischemia was induced by adjusting inflow into the cannulated left
      anterior coronary artery to reduce coronary arterial pressure to 45 mm Hg (ISCH);
      4 pigs received the inducible nitric oxide synthase (iNOS) inhibitors
      aminoguanidine or L-N(6)-(1-iminoethyl)-lysine during ISCH (ISCH+iNOS-Inhib); 6
      pigs served as controls (SHAM). Anterior (AW) and posterior (PW) systolic wall
      thickening (sonomicrometry) were measured. After 6 hours, nitric oxide (NO)
      synthase (NOS) protein expression, NOS activity, and NO metabolites
      (nitrite/nitrate/nitroso species) were quantified in biopsies isolated from AW
      and PW. Cardiomyocyte shortening and intracellular calcium (Indo-1 acetoxymethyl
      ester) were measured without and with the NOS substrate L-arginine (100
      micromol/L). In ISCH, AW wall thickening decreased from 42+/-4% (baseline) to
      16+/-3% (6 hours). Wall thickening remained unchanged in ISCH-PW and SHAM-AW/PW.
      NOS2 (iNOS) protein expression and activity, but not NOS3 (endothelial NO
      synthase), were increased in ISCH-AW and ISCH-PW. iNOS expression correlated with
      increased nitrite contents. Cardiomyocyte shortening was reduced in ISCH-AW
      versus SHAM-AW (4.4+/-0.3% versus 5.6+/-0.3%). L-Arginine reduced cardiomyocyte
      shortening further in ISCH-AW (to 2.8+/-0.2%) and ISCH-PW (3.4+/-0.4% versus
      5.4+/-0.4%) but not in SHAM or in ISCH+iNOS-Inhib; intracellular [Ca(2+)]
      remained unchanged. With L-arginine, in vitro AW cardiomyocyte shortening
      correlated with in vivo AW wall thickening (r=0.72). In conclusion, sustained
      regional ischemia induces myocardial iNOS expression in pigs, which contributes
      to contractile dysfunction at the cardiomyocyte level.

PMID- 18818405
TI  - Thrombospondin-1 deficiency accelerates atherosclerotic plaque maturation in ApoE
      /- mice.
AB  - Thrombospondin (TSP)1 is implicated in various inflammatory processes, but its
      role in atherosclerotic plaque formation and progression is unclear. Therefore,
      the development of atherosclerosis was compared in ApoE(-/-) and Tsp1(-/-)ApoE(-/
      ) mice kept on a normocholesterolemic diet. At 6 months, morphometric analysis of
      the aortic root of both mouse genotypes showed comparable lesion areas. Even when
      plaque burden increased approximately 5-fold in ApoE(-/-) and 10-fold in Tsp1(-/
      )ApoE(-/-) mice, during the subsequent 3 months, total plaque areas were
      comparable at 9 months. In contrast, plaque composition differed substantially
      between genotypes: smooth muscle cell areas, mostly located in the fibrous cap of
      ApoE(-/-) plaques, both at 6 and 9 months, were 3-fold smaller in Tsp1(-/-)ApoE(
      /-) plaques, which, in addition, were also more fibrotic. Moreover, inflammation
      by macrophages was twice as high in Tsp1(-/-)ApoE(-/-) plaques. This correlated
      with a 30-fold elevated incidence of elastic lamina degradation, with matrix
      metalloproteinase-9 accumulation, underneath plaques and manifestation of
      ectasia, exclusively in Tsp1(-/-)ApoE(-/-) mice. At 9 months, the necrotic core
      was 1.4-fold larger and 4-fold higher numbers of undigested disintegrated
      apoptotic cells were found in Tsp1(-/-)ApoE(-/-) plaques. Phagocytosis of
      platelets by cultured Tsp1(-/-) macrophages revealed the instrumental role of
      TSP1 in phagocytosis, corroborating the defective intraplaque phagocytosis of
      apoptotic cells. Hence, the altered smooth muscle cell phenotype in Tsp1(-/
      )ApoE(-/-) mice has limited quantitative impact on atherosclerosis, but defective
      TSP1-mediated phagocytosis enhanced plaque necrotic core formation, accelerating
      inflammation and macrophage-induced elastin degradation by metalloproteinases,
      speeding up plaque maturation and vessel wall degeneration.

PMID- 18818406
TI  - VEGF-A stimulates ADAM17-dependent shedding of VEGFR2 and crosstalk between
      VEGFR2 and ERK signaling.
AB  - Vascular endothelial growth factor (VEGF)-A and the VEGF receptors are critical
      for regulating angiogenesis during development and homeostasis and in
      pathological conditions, such as cancer and proliferative retinopathies. Most
      effects of VEGF-A are mediated by the VEGFR2 and its coreceptor, neuropilin (NRP)
      1. Here, we show that VEGFR2 is shed from cells by the metalloprotease
      disintegrin ADAM17, whereas NRP-1 is released by ADAM10. VEGF-A enhances VEGFR2
      shedding by ADAM17 but not shedding of NRP-1 by ADAM10. VEGF-A activates ADAM17
      via the extracellular signal-regulated kinase (ERK) and mitogen-activated protein
      kinase pathways, thereby also triggering shedding of other ADAM17 substrates,
      including tumor necrosis factor alpha, transforming growth factor alpha, heparin
      binding epidermal growth factor-like growth factor, and Tie-2. Interestingly, an
      ADAM17-selective inhibitor shortens the duration of VEGF-A-stimulated ERK
      phosphorylation in human umbilical vein endothelial cells, providing evidence for
      an ADAM17-dependent crosstalk between the VEGFR2 and ERK signaling. Targeting the
      sheddases of VEGFR2 or NRP-1 might offer new opportunities to modulate VEGF-A
      signaling, an already-established target for treatment of pathological
      neovascularization.

PMID- 18818407
TI  - Pathophysiological levels of soluble P-selectin mediate adhesion of leukocytes to
      the endothelium through Mac-1 activation.
AB  - Plasma soluble P-selectin (sP-selectin) levels are increased in pathologies
      associated with atherosclerosis, including peripheral arterial occlusive disease
      (PAOD). However, the role of sP-selectin in regulating leukocyte-endothelial
      adhesion is unclear. The aim of this study was to assess the ability of exogenous
      and endogenous sP-selectin to induce leukocyte responses that promote their
      adhesion to various forms of endothelium. In flow chamber assays, sP-selectin
      dose-dependently increased neutrophil adhesion to resting human iliac artery
      endothelial cells. Similarly, sP-selectin induced neutrophil adhesion to the
      endothelial surface of murine aortae and human radial venous segments in ex vivo
      flow chamber experiments. Using intravital microscopy to examine postcapillary
      venules in the mouse cremaster muscle, in vivo administration of sP-selectin was
      also found to significantly increase leukocyte rolling and adhesion in
      unstimulated postcapillary venules. Using a Mac-1-specific antibody and P
      selectin knockout mouse, it was demonstrated that this finding was dependent on a
      contribution of Mac-1 to leukocyte rolling and endothelial P-selectin expression.
      This was confirmed in an ex vivo perfusion model using viable mouse aorta and
      human radial vessels. In contrast, with tumor necrosis factor-alpha-activated
      endothelial cells and intact endothelium, where neutrophil adhesion was already
      elevated, sP-selectin failed to further increase adhesion. Plasma samples from
      PAOD patients containing pathologically elevated concentrations of sP-selectin
      also increased neutrophil adhesion to the endothelium in a sP-selectin-dependent
      manner, as demonstrated by immunodepletion of sP-selectin. These studies
      demonstrate that raised plasma sP-selectin may influence the early progression of
      vascular disease by promoting leukocyte adhesion to the endothelium in PAOD,
      through Mac-1-mediated rolling and dependent on endothelial P-selectin
      expression.

PMID- 18818408
TI  - Mechanisms underlying erythrocyte and endothelial nitrite reduction to nitric
      oxide in hypoxia: role for xanthine oxidoreductase and endothelial nitric oxide
      synthase.
AB  - Reduction of nitrite (NO(2)(-)) provides a major source of nitric oxide (NO) in
      the circulation, especially in hypoxemic conditions. Our previous studies suggest
      that xanthine oxidoreductase (XOR) is an important nitrite reductase in the heart
      and kidney. Herein, we have demonstrated that conversion of nitrite to NO by
      blood vessels and RBCs was enhanced in the presence of the XOR substrate xanthine
      (10 micromol/L) and attenuated by the XOR inhibitor allopurinol (100 micromol/L)
      in acidic and hypoxic conditions only. Whereas endothelial nitric oxide synthase
      (eNOS) inhibition had no effect on vascular nitrite reductase activity, in RBCs L
      NAME, L-NMMA, and L-arginine inhibited nitrite-derived NO production by >50%
      (P<0.01) at pH 7.4 and 6.8 under hypoxic conditions. Western blot and
      immunohistochemical analysis of RBC membranes confirmed the presence of eNOS and
      abundant XOR on whole RBCs. Thus, XOR and eNOS are ideally situated on the
      membranes of RBCs and blood vessels to generate intravascular vasodilator NO from
      nitrite during ischemic episodes. In addition to the proposed role of
      deoxyhemoglobin, our findings suggest that the nitrite reductase activity within
      the circulation, under hypoxic conditions (at physiological pH), is mediated by
      eNOS; however, as acidosis develops, a substantial role for XOR becomes evident.

PMID- 18818409
TI  - Atrial Fibrillation and Other Clinical Manifestations of Altered TBX5 Dosage in
      Typical Holt-Oram Syndrome.

PMID- 18818410
TI  - NFAT-dependent excitation-transcription coupling in heart.

PMID- 18818411
TI  - Biological surgery: synergetic angiogenic therapy using coadministration of two
      progenitor cell populations.

PMID- 18818412
TI  - Zinc fingers in the pizza pie aorta.

PMID- 18818413
TI  - Athsq1 is an atherosclerosis modifier locus with dramatic effects on lesion area
      and prominent accumulation of versican.
AB  - OBJECTIVE: Susceptibility to atherosclerosis is genetically complex, and modifier
      genes that do not operate via traditional risk factors are largely unknown. A
      mouse genetics approach can simplify the genetic analysis and provide tools for
      mechanistic studies. METHODS AND RESULTS: We previously identified
      atherosclerosis susceptibility QTL (Athsq1) on chromosome 4 acting independently
      of systemic risk factors. We now report confirmation of this locus in congenic
      strains carrying the MOLF-derived susceptibility allele in the C57BL/6J-Ldlr(-/-)
      genetic background. Homozygous congenic mice exhibited up to 4.5-fold greater
      lesion area compared to noncongenic littermates (P<0.0001). Analysis of
      extracellular matrix composition revealed prominent accumulation of versican, a
      presumed proatherogenic matrix component abundant in human lesions but almost
      absent in the widely-used C57BL/6 murine atherosclerosis model. The results of a
      bone marrow transplantation experiment suggested that both accelerated lesion
      development and versican accumulation are mediated, at least in part, by
      macrophages. Interestingly, comparative mapping revealed that the Athsq1 congenic
      interval contains the mouse region homologous to a widely-replicated CHD locus on
      human chromosome 9p21. CONCLUSIONS: These studies confirm the proatherogenic
      activity of a novel gene(s) in the MOLF-derived Athsq1 locus and provide in vivo
      evidence for a causative role of versican in lesion development.

PMID- 18818414
TI  - Advanced glycation end-product of low density lipoprotein activates the toll-like
      4 receptor pathway implications for diabetic atherosclerosis.
AB  - OBJECTIVE: Diabetes is a major risk factor for coronary heart disease.
      Accumulation of advanced glycation end-products (AGEs) attributable to
      hyperglycemia in diabetics promotes the development of atherosclerosis. However,
      the underlying mechanisms remain unclear. METHODS AND RESULTS: The advanced
      glycation end-product of low-density-lipoprotein (AGE-LDL) induced
      proinflammatory cytokine production in human coronary artery endothelial cells
      and human- and mouse-macrophages. AGE-LDL stimulated cytokine synthesis was
      markedly reduced in mouse macrophages with a TLR4 loss-of-function mutation.
      Coimmunoprecipitation experiments indicated AGE-LDL interacts with TLR4, RAGE,
      and CD36. Incubation of cultured macrophages with TLR4, RAGE, or CD36 antibodies
      inhibited AGE-LDL stimulation of tumor necrosis factor (TNF)alpha production. A
      competitive binding inhibitor of TLR4 blocked AGE-LDL binding to the receptor.
      After transfection of a HEK293 cell system with wild-type TLR4, AGE-LDL activated
      a signaling pathway including p38 alpha, JNK, and ERK1 kinases and AP1, Elk1, and
      NF-kappaB transcription factors; the net result being increased cytokine
      production. These effects were absent when cells were transfected with empty
      plasmid. Two common polymorphisms in TLR4, D299G and T399I, reduced the response
      of TLR4 to lipopolysaccharide (LPS) but had no effect on AGE-LDL signaling.
      CONCLUSIONS: These results indicate that AGE-LDL activates a TLR4-mediated
      signaling pathway, thus inducing proinflammatory cytokine production. This
      mechanism may partly explain the increased risk of atherosclerosis observed in
      diabetics.

PMID- 18818415
TI  - Pioglitazone inhibits the expression of inflammatory cytokines from both
      monocytes and lymphocytes in patients with impaired glucose tolerance.
AB  - OBJECTIVE: The current study determines whether pioglitazone (PIO) therapy
      reduces both monocyte and lymphocyte inflammatory activity and their ability to
      induce inflammation in other tissues. METHODS AND RESULTS: Monocyte and
      lymphocyte cytokine gene and protein expression of interleukin (IL)-6 were first
      shown to be greater in subjects with impaired glucose tolerance (IGT) than in
      subjects with normal glucose tolerance. Sixty-six IGT subjects were then
      randomized to 4,5 months of placebo or PIO therapy. After receiving PIO, subjects
      had lower triglycerides and higher HDL cholesterol (P<0.05) than did subjects
      receiving placebo. Monocyte gene and protein expression of IL-1 beta, IL-6, and
      IL-8 (and IL-2, IL-6 and IL-8 from lymphocytes) was significantly lower after PIO
      therapy in the resting state, as well as after lipopolysaccharide (LPS)
      stimulation (P<0.05 for all). Moreover, IL-6, IL-8, and MCP-1 gene expression
      were decreased by nearly 50% in human adipocytes exposed to conditioned media
      from monocytes or lymphocytes from PIO treated subjects. CONCLUSIONS: These
      results demonstrate that PIO therapy in IGT can reduce proinflammatory gene and
      protein expression from both monocytes and lymphocytes. This intervention also
      reduces the inflammatory cross-talk between these immune cells and adipose
      tissue, which could in turn contribute to the metabolic improvements resulting
      from PIO therapy.

PMID- 18818416
TI  - Deficiency and inhibition of cathepsin K reduce body weight gain and increase
      glucose metabolism in mice.
AB  - OBJECTIVE: Previous studies demonstrated increased levels of cysteine proteases
      cathepsins in serum and adipose tissues from obese patients. We now provide
      evidence from a mouse model of obesity to suggest a direct participation of
      cathepsin K (CatK) in mouse body weight gain and glucose metabolism. METHODS AND
      RESULTS: Using real-time polymerase chain reaction, we detected 12-fold increase
      in CatK transcripts after adipogenesis of human preadipocytes. Using an
      immunohistology analysis, we consistently observed high levels of CatK expression
      in adipose tissues from obese humans and mice. Selective inhibition of CatK
      activity blocked the lipid accumulation in human and mouse preadipocytes. In
      mice, CatK deficiency reduced significantly diet-induced body weight gain and
      serum glucose and insulin levels. Similar results were obtained in diet-induced
      and genetically created (ob/ob) obese mice after animals were treated with a CatK
      selective inhibitor. Mechanistic study demonstrated a role for CatK in degrading
      fibronectin, a matrix protein that controls adipogenesis. Deficiency or
      inhibition of CatK leads to fibronectin accumulation in muscle and adipose
      tissues. CONCLUSIONS: This study demonstrates an essential role of CatK in
      adipogenesis and mouse body weight gain, possibly via degradation of fibronectin,
      thus suggesting a novel therapeutic strategy for the control of obesity by
      regulating CatK activity.

PMID- 18818417
TI  - Notch3 is a major regulator of vascular tone in cerebral and tail resistance
      arteries.
AB  - OBJECTIVE: Notch3, a member of the evolutionary conserved Notch receptor family,
      is primarily expressed in vascular smooth muscle cells. Genetic studies in human
      and mice revealed a critical role for Notch3 in the structural integrity of
      distal resistance arteries by regulating arterial differentiation and postnatal
      maturation. METHODS AND RESULTS: We investigated the role of Notch3 in vascular
      tone in small resistance vessels (tail and cerebral arteries) and large (carotid)
      arteries isolated from Notch3-deficient mice using arteriography. Passive
      diameter and compliance were unaltered in mutant arteries. Similarly,
      contractions to phenylephrine, KCl, angiotensin II, and thromboxane A2 as well as
      dilation to acetylcholine or sodium nitroprusside were unaffected. However,
      Notch3 deficiency induced a dramatic reduction in pressure-induced myogenic tone
      associated with a higher flow (shear stress)-mediated dilation in tail and
      cerebral resistance arteries only. Furthermore, RhoA activity and myosin light
      chain phosphorylation, measured in pressurized tail arteries, were significantly
      reduced in Notch3KO mice. Additionally, myogenic tone inhibition by the Rho
      kinase inhibitor Y27632 was attenuated in mutant tail arteries. CONCLUSIONS:
      Notch3 plays an important role in the control of vascular mechano-transduction,
      by modulating the RhoA/Rho kinase pathway, with opposite effects on myogenic tone
      and flow-mediated dilation in the resistance circulation.

PMID- 18818418
TI  - Myocyte specific overexpression of myoglobin impairs angiogenesis after hind-limb
      ischemia.
AB  - OBJECTIVE: In preclinical models of peripheral arterial disease the angiogenic
      response is typically robust, though it can be impaired in conditions such as
      hypercholesterolemia and diabetes where the endothelium is dysfunctional.
      Myoglobin (Mb) is expressed exclusively in striated muscle cells. We hypothesized
      that myocyte specific overexpression of myoglobin attenuates ischemia-induced
      angiogenesis even in the presence of normal endothelium. METHODS AND RESULTS: Mb
      overexpressing transgenic (MbTg, n=59) and wild-type (WT, n=56) C57Bl/6 mice
      underwent unilateral femoral artery ligation/excision. Perfusion recovery was
      monitored using Laser Doppler. Ischemia-induced changes in muscle were assessed
      by protein and immunohistochemistry assays. Nitrite/nitrate and protein-bound NO,
      and vasoreactivity was measured. Vasoreactivity was similar between MbTg and WT.
      In ischemic muscle, at d14 postligation, MbTg increased VEGF-A, and activated
      eNOS the same as WT mice but nitrate/nitrite were reduced whereas protein-bound
      NO was higher. MbTg had attenuated perfusion recovery at d21 (0.37+/-0.03 versus
      0.47+/-0.02, P<0.05), d28 (0.40+/-0.03 versus 0.50+/-0.04, P<0.05), greater limb
      necrosis (65.2% versus 15%, P<0.001), a lower capillary density, and greater
      apoptosis versus WT. CONCLUSIONS: Increased Mb expression in myocytes attenuates
      angiogenesis after hind-limb ischemia by binding NO and reducing its
      bioavailability. Myoglobin can modulate the angiogenic response to ischemia even
      in the setting of normal endothelium.

PMID- 18818419
TI  - Bone morphogenetic proteins 2 and 4 are selectively expressed by late outgrowth
      endothelial progenitor cells and promote neoangiogenesis.
AB  - OBJECTIVE: Endothelial progenitor cells are currently identified either by their
      surface antigen expression or by their generation of early colonies in culture
      (CFU-Hill). Another population, endothelial colony-forming cells (ECFCs), has
      strong vessel-forming capacity but is less well characterized. Given the
      potential usefulness of CFU-Hill and ECFCs as cell therapy products, their
      thorough characterization is of major importance. METHODS AND RESULTS: CFU-Hill
      and ECFCs were expanded from human cord and adult blood. Bone morphogenetic
      proteins 2 and 4 (BMP2/4) were selectively expressed by ECFCs but not by CFU
      Hill. The BMP pathway was involved in ECFC commitment and angiogenic potential in
      vitro. In vivo, BMP inhibition strongly reduced plug vascularization in bFGF
      containing Matrigel plugs implanted in C57/Bl6 mice. Moreover, ECFC exposure to
      BMP increased their therapeutic potential in a nude mouse model of hindlimb
      ischemia. In amputation specimens from patients with critical leg ischemia who
      had received a local therapeutic injection of bone marrow mononuclear cells,
      newly formed vessels were strongly positive for BMP2/4, suggesting that
      endothelial cells involved in neovascularization have an ECFC-like phenotype.
      CONCLUSIONS: BMP2/4 are a marker of ECFCs and play a key role in ECFC commitment
      and outgrowth during neovascularization.

PMID- 18818420
TI  - Inhibition of CCR2 ameliorates insulin resistance and hepatic steatosis in db/db
      mice.
AB  - OBJECTIVE: Recently, adipose tissue inflammation induced by macrophage
      infiltration through MCP-1/C-C chemokine receptor-2 (CCR2) pathway is considered
      to play a role in the development of visceral obesity and insulin resistance. In
      the present study, to further examine the role of CCR2 in the development of
      obesity and type 2 diabetes, we studied the effect of pharmacological inhibition
      of CCR2 from the early stage of obesity in db/db mice. METHODS AND RESULTS: Db/+m
      (lean control) and db/db mice were fed with a standard diet with or without
      0.005% propagermanium, as a CCR2 inhibitor for 12 weeks from 6 weeks of age.
      Propagermanium treatment decreased body weight gain, visceral fat accumulation,
      and the size of adipocytes only in db/db mice. Further, propagermanium suppressed
      macrophage accumulation and inflammation in adipose tissue. Propagermanium
      treatment also ameliorated glucose tolerance and insulin sensitivity, and
      decreased hepatic triglyceride contents in db/db mice. CONCLUSIONS:
      Propagermanium improved obesity and related metabolic disorders, such as insulin
      resistance and hepatic steatosis by suppressing inflammation in adipose tissue.
      Our data indicate that inhibition of CCR2 could improve obesity and type 2
      diabetes by interfering adipose tissue inflammation, and that propagermanium may
      be a beneficial drug for the treatment of the metabolic syndrome.

PMID- 18818421
TI  - Chemokines in vascular dysfunction and remodeling.
AB  - Vascular remodeling stands for structural changes of the vessel wall in response
      to various noxious stimuli, which results in reorganization of the vessel wall
      architecture. Luminal narrowing because of neointima formation and constrictive
      remodeling leading to hypoperfusion is the most relevant clinical effect. Smooth
      muscle cell (SMC) accumulation, inflammatory cell recruitment, and endothelial
      regeneration are the critical parts in obstructive vascular remodeling.
      Chemokines and chemokine receptors have a great impact on initiating and
      progressing neointimal formation by controlling each step of the remodeling
      process. SDF-1alpha regulates vascular repair by CXCR4-dependent smooth muscle
      progenitor cell recruitment, which contributes to the maladaptive response to
      injury. The three distinct chemokine-chemokine receptor pairs MCP-1/CCR2,
      RANTES/CCR5, and Fractalkine/CX(3)CR1 direct lesional leukocyte infiltration. In
      addition MCP-1/CCR2 and Fractalkine/CX(3)CR1 increase neointimal SMC expansion.
      In contrast, KC/Gro-alpha supports endothelial recovery through CXCR2, which
      attenuates neointima formation. These findings highlight the importance to
      characterize specific functions of the chemokine network to enable therapeutic
      intervention.

PMID- 18818422
TI  - A strategy to reveal potential glycan markers from serum glycoproteins associated
      with breast cancer progression.
AB  - Aberrant glycosylation on glycoproteins that are either presented on the surface
      or secreted by cancer cells is a potential source of disease biomarkers and
      provides insights into disease pathogenesis. N-Glycans of the total serum
      glycoproteins from advanced breast cancer patients and healthy individuals were
      sequenced by HPLC with fluorescence detection coupled with exoglycosidase
      digestions and mass spectrometry. We observed a significant increase in a
      trisialylated triantennary glycan containing alpha1,3-linked fucose which forms
      part of the sialyl Lewis x epitope. Following digestion of the total glycan pool
      with a combination of sialidase and beta-galactosidase, we segregated and
      quantified a digestion product, a monogalactosylated triantennary structure
      containing alpha1,3-linked fucose. We compared breast cancer patients and
      controls and detected a 2-fold increase in this glycan marker in patients. In 10
      patients monitored longitudinally, we showed a positive correlation between this
      glycan marker and disease progression and also demonstrated its potential as a
      better indicator of metastasis compared to the currently used biomarkers, CA 15-3
      and carcinoembryonic antigen (CEA). A pilot glycoproteomic study of advanced
      breast cancer serum highlighted acute-phase proteins alpha1-acid glycoprotein,
      alpha1-antichymotrypsin, and haptoglobin beta-chain as contributors to the
      increase in the glycan marker which, when quantified from each of these proteins,
      marked the onset of metastasis in advance of the CA 15-3 marker. These
      preliminary findings suggest that specific glycans and glycoforms of proteins may
      be candidates for improved markers in the monitoring of breast cancer
      progression.

PMID- 18818423
TI  - Inhibition of the interaction between the SARS-CoV spike protein and its cellular
      receptor by anti-histo-blood group antibodies.
AB  - Severe acute respiratory syndrome coronavirus (SARS-CoV) is a highly pathogenic
      emergent virus which replicates in cells that can express ABH histo-blood group
      antigens. The heavily glycosylated SARS-CoV spike (S) protein binds to
      angiotensin-converting enzyme 2 which serves as a cellular receptor.
      Epidemiological analysis of a hospital outbreak in Hong Kong revealed that blood
      group O was associated with a low risk of infection. In this study, we used a
      cellular model of adhesion to investigate whether natural antibodies of the ABO
      system could block the S protein and angiotensin-converting enzyme 2 interaction.
      To this aim, a C-terminally EGFP-tagged S protein was expressed in chinese
      hamster ovary cells cotransfected with an alpha1,2-fucosyltransferase and an A
      transferase in order to coexpress the S glycoprotein ectodomain and the A antigen
      at the cell surface. We observed that the S protein/angiotensin-converting enzyme
      2-dependent adhesion of these cells to an angiotensin-converting enzyme 2
      expressing cell line was specifically inhibited by either a monoclonal or human
      natural anti-A antibodies, indicating that these antibodies may block the
      interaction between the virus and its receptor, thereby providing protection. In
      order to more fully appreciate the potential effect of the ABO polymorphism on
      the epidemiology of SARS, we built a mathematical model of the virus transmission
      dynamics that takes into account the protective effect of ABO natural antibodies.
      The model indicated that the ABO polymorphism could contribute to substantially
      reduce the virus transmission, affecting both the number of infected individuals
      and the kinetics of the epidemic.

PMID- 18818425
TI  - Racial disparities in access to long-term care: the illusive pursuit of equity.
AB  - While nursing homes were insulated from civil-rights enforcement at the time of
      the implementation of the Medicare program and lagged behind other parts of the
      health sector in providing comparable access to minorities, they are the only
      providers for which current reporting requirements make it possible to fully
      assess racial disparities in use and quality of care. We find that African
      Americans' use of nursing homes in 2000 in the United States was 14 percent
      higher than Caucasians' use. The largest relative African American use of nursing
      homes in 2000 took place in the South and West. Average nursing-home case-mix
      acuity for African Americans and Caucasians were essentially identical,
      suggesting that shifts in payment incentives have eliminated the selective
      admission of easy-care private-pay (predominantly Caucasian) patients and helped
      fuel the growth of private pay home care and assisted living for this segment of
      the population. While these shifts in incentives helped increase the use of
      nursing homes by African Americans, a high degree of segregation and disparity in
      the quality of the nursing homes used by African Americans persists. Parity in
      use is an illusive benchmark for measuring progress in assuring equity in
      treatment.

PMID- 18818426
TI  - Receipt of preventive dental care among special-needs children enrolled in
      Medicaid: a crisis in need of attention.
AB  - Although not widely recognized, tooth decay is the most common childhood chronic
      disease among children ages five to seventeen. Despite higher rates of dental
      caries and greater needs, low-income minority children enrolled in Medicaid are
      more likely to go untreated relative to their higher income counterparts. No
      research has examined this issue for children with special needs. We analyzed
      Medicaid enrollment and claims data for special-needs children enrolled in the
      District of Columbia Medicaid program to evaluate receipt of recommended
      preventive dental care. Use of preventive dental care is abysmally low and has
      declined over time. Enrollment in managed care rather than fee for service
      improves the likelihood that special-needs children receive recommended
      preventive dental services, whereas residing farther from the Metro is an
      impediment to receipt of dental care.

PMID- 18818427
TI  - Promoting a "good death": determinants of pain-management policies in the United
      States.
AB  - Many Americans do not experience a good death. The inadequate treatment of pain
      at the end of life has been associated with a lack of supportive public policies
      more than a lack of evidence-based clinical practices or organizational efforts.
      Given a widespread lack of understanding about pain policies, we examine the
      critical role played by state medical boards in developing pain policies and then
      apply event history analysis to identify the variables most critical to the
      formation of these policies. We develop an integrated model and evaluate the
      adoption of eight different types of pain policies. The analytic models
      incorporate fifteen years of observational data and test the impact of
      contextual, political, extrinsic, and institutional variables. They reveal that
      the presence of legal counselors on state medical boards has consistently
      increased the likelihood that state boards adopt policies associated with
      progressive pain management. Further, policy has been negatively influenced by
      historical activity: boards that previously adopted one pain policy have been
      less likely to subsequently adopt additional pain policies. This work illuminates
      mechanisms behind state pain-policy adoption and provides valuable information
      for advocates who seek to improve pain-management policy and reduce the amount of
      pain at the end of life.

PMID- 18818428
TI  - Rebates and spreads: pharmacy benefit management practices and corporate
      citizenship.
AB  - How ought we determine whether businesses in the health care sector profit
      fairly? One class of companies in the health care sector, pharmacy benefit
      managers (PBMs), deserves special consideration. We describe two specific revenue
      generating practices--rebates and spread pricing--that account significantly for
      PBMs' profits but have been neglected in the bioethics and health policy
      literature as important sources of fiscal waste in our current health care
      system. We offer analyses of two common cases, consider employers' and employees'
      vulnerabilities, explore normative assumptions about how markets function, and
      raise questions about transparency in contract agreements between PBMs and
      employers. We consider ethical dimensions of PBMs' corporate citizenship in the
      health care sector and suggest how employers can negotiate more effectively with
      PBMs.

PMID- 18818431
TI  - Health care financing reforms in Germany: the case for rethinking the
      evolutionary approach to reforms.
AB  - Health care reform has been a perpetual issue in German politics since
      reunification. Reform initially focused on restructuring the health care system
      of the former East Germany. It has subsequently focused on questioning whether
      the financing of the German social health insurance (SHI) system is sustainable,
      in light of economic malaise that characterized the 1990s and heightened global
      competition. In this article, we document twelve significant attempts to reform
      health care financing in Germany and critically appraise them according to the
      principles of solidarity and subsidiarity on which SHI systems were built. While
      the reforms in the aggregate offered the prospect of addressing the challenges
      faced by the system, the modest results of the reforms and remaining deficiencies
      of the system underscore the limitations of the evolutionary approach to reforms.
      This suggests that reformers should consider a more revolutionary approach.

PMID- 18818432
TI  - Surgical release for proximal hamstring syndrome.
AB  - BACKGROUND: Pain in the buttock radiating to the popliteal fossa associated with
      hamstring weakness can be caused by tethering of the sciatic nerve to the
      proximal hamstring tendons. Contraction of the hamstring muscles produces
      traction on the sciatic nerve and subsequent symptoms. HYPOTHESIS: Surgical
      release of the proximal hamstring tendons, in particular from the sciatic nerve,
      will improve symptoms and function. STUDY DESIGN: Case series; Level of evidence,
      4. METHODS: Forty-seven proximal hamstring surgical releases were performed in 44
      patients (28 males, 16 females). The initial clinical findings and imaging were
      obtained from the medical notes, and additional data were obtained from a later
      questionnaire. The average age at the time of surgery was 29 years (range, 15-58
      years). All patients were involved in high-level sports. Long-term follow-up was
      with a comprehensive postal questionnaire. RESULTS: Full follow-up was obtained
      in 43 patients (46 operations). Average follow-up was 53 months (range, 9-110).
      No major complications were encountered from the surgery. The average visual
      analog scale pain score decreased from 6.5 preoperatively to 2.0 (P < .001). Two
      patients had increased pain, and pain was unchanged in 4. The average subjective
      weakness score decreased from 6.6 to 2.8 (P < .001). Three patients reported
      increased weakness at follow-up, and 3 patients reported that the hamstring
      muscles felt equally weak. Thirty-four patients (77%) had returned to their
      previous sporting activities, with 30 patients still competing at or above state
      level, or professionally, after surgery. The average satisfaction score was 7.8.
      Six patients (14%) were not satisfied with the outcome of the procedure, 5
      patients (11%) were somewhat satisfied, and 33 patients (75%) were very
      satisfied. CONCLUSION: Proximal hamstring syndrome occurs mainly in patients
      participating in competitive sports. Release of the proximal hamstring tendons in
      this active group resulted in decreased pain and increased strength, and the
      majority of patients were satisfied with the procedure.

PMID- 18818433
TI  - Semitendinosus tendon graft versus a modified Weaver-Dunn procedure for
      acromioclavicular joint reconstruction in chronic cases: a prospective
      comparative study.
AB  - BACKGROUND: Biomechanical studies comparing various surgical techniques for
      acromioclavicular joint reconstruction have reported that semitendinosus tendon
      graft for coracoclavicular ligament reconstruction provides a substantial
      improvement in initial stability and a load-to-failure equivalent to the intact
      coracoclavicular ligaments. Although it represents a biomechanical improvement
      compared with coracoacromial ligament transfer, there is still a lack of
      prospective comparative studies confirming the clinical relevance of these
      biomechanical findings. HYPOTHESIS: Semitendinosus tendon graft for
      coracoclavicular ligament reconstruction is associated with superior clinical
      results compared with a modified Weaver-Dunn procedure in chronic complete
      acromioclavicular joint dislocation. STUDY DESIGN: Cohort study; Level of
      evidence, 2. METHODS: Twenty-four patients (mean age, 42 years) with painful,
      chronic Rockwood type III through V acromioclavicular joint dislocations were
      subjected to surgical reconstruction. In 12 patients, a modified Weaver-Dunn
      procedure was performed; in the other 12 patients, autogenous semitendinosus
      tendon graft was used. Clinical evaluation was performed using the American
      Shoulder and Elbow Surgeons shoulder score and the Constant score after a mean
      follow-up time of 37 months. Preoperative and postoperative radiographs were
      compared. RESULTS: The mean American Shoulder and Elbow Surgeons shoulder score
      improved from 74 +/- 7 points preoperatively to 86 +/- 8 points postoperatively
      in the Weaver-Dunn group, and from 74 +/- 4 points to 96 +/- 5 points in the
      semitendinosus tendon group (P < .001 for both techniques). The mean Constant
      score improved from 70 +/- 8 points to 81 +/- 8 points in the Weaver-Dunn group,
      and from 71 +/- 5 points to 93 +/- 7 points in the semitendinosus tendon group (P
      < .001). The results in the semitendinosus tendon group were significantly better
      than in the Weaver-Dunn group (P < .001). The radiologic measurements showed a
      mean coracoclavicular distance of 12.3 +/- 4 mm in the Weaver-Dunn group
      increasing to 14.9 +/- 6 mm under stress loading, compared with 11.4 +/- 3 mm
      increasing to 11.8 +/- 3 mm under stress in the semitendinosus tendon group. The
      difference during stress loading was statistically significant (P = .027). In the
      semitendinosus tendon group, horizontal displacement of the lateral clavicle end
      could be reduced in all cases with type IV dislocation. CONCLUSION:
      Semitendinosus tendon graft for coracoclavicular ligament reconstruction resulted
      in significantly superior clinical and radiologic outcomes compared to the
      modified Weaver-Dunn procedure.

PMID- 18818434
TI  - Adipose stromal/stem cells: basic and translational advances: the IFATS
      collection.

PMID- 18818435
TI  - 1,4,5-Inositol trisphosphate-operated intracellular Ca(2+) stores and angiotensin
      II/endothelin-1 signaling pathway are functional in human embryonic stem cell
      derived cardiomyocytes.
AB  - On the basis of previous findings suggesting that in human embryonic stem cell
      derived cardiomyocytes (hESC-CM) the sarcoplasmic reticulum Ca(2+)-induced
      release of calcium machinery is either absent or immature, in the present study
      we tested the hypothesis that hESC-CM contain fully functional 1,4,5-inositol
      trisphosphate (1,4,5-IP(3))-operated intracellular Ca(2+) ([Ca(2+)](i)) stores
      that can be mobilized upon appropriate physiological stimuli. To test this
      hypothesis we investigated the effects of angiotensin-II (AT-II) and endothelin-1
      (ET-1), which activate the 1,4,5-IP(3) pathway, on [Ca(2+)](i) transients and
      contractions in beating clusters of hESC-CM. Our major findings were that in
      paced hESC-CM both AT-II and ET-1 (10(-9) to 10(-7) M) increased the contraction
      amplitude and the maximal rates of contraction and relaxation. In addition, AT-II
      (10(-9) to 10(-7) M) increased the [Ca(2+)](i) transient amplitude. The
      involvement of 1,4,5-IP(3)-dependent intracellular Ca(2+) release in the
      inotropic effect of AT-II was supported by the findings that (a) hESC-CM express
      AT-II, ET-1, and 1,4,5-IP(3) receptors determined by immunofluorescence staining,
      and (b) the effects of AT-II were blocked by 2 microM 2-aminoethoxyphenyl borate
      (a 1,4,5-IP(3) receptor blocker) and U73122 (a phospholipase C blocker). In
      conclusion, these findings demonstrate for the first time that hESC-CM exhibit
      functional AT-II and ET-1 signaling pathways, as well as 1,4,5-IP(3)-operated
      releasable Ca(2+) stores.

PMID- 18818436
TI  - Analysis of extracellular signal-regulated kinase 2 function in neural
      stem/progenitor cells via nervous system-specific gene disruption.
AB  - Extracellular signal-regulated kinase 2 (ERK2) is involved in a variety of cell
      fate decisions during development, but its exact role in this process remains to
      be determined. To specifically focus on the role of ERK2 in the brain, and to
      avoid early lethalities, we used a conditional gene-targeting approach to
      preferentially inactivate Erk2 in the embryonic mouse brain. The resulting mutant
      mice were viable and were relatively normal in overall appearance. However, the
      loss of Erk2 resulted in a diminished proliferation of neural stem cells in the
      embryonic ventricular zone (VZ), although the survival and differentiation of
      these cells was unaffected. The multipotent neural progenitor cells (NPCs)
      isolated from ERK2-deficient brains also showed impaired proliferation, reduced
      self-renewal ability, and increased apoptosis. By neurosphere differentiation
      analysis we further observed that lineage-restricted glial progenitors were
      increased in ERK2-deficient mice. The decline in the self-renewal ability and
      multipotency of NPCs resulting from the loss of ERK2 was found to be caused at
      least in part by upregulation of the JAK-STAT signaling pathway and reduced G1/S
      cell cycle progression. Furthermore, by global expression analysis we found that
      neural stem cell markers, including Tenascin C NR2E1 (Tlx), and Lgals1 (Galectin
      1), were significantly downregulated, whereas several glial lineage markers were
      upregulated in neurospheres derived from ERK2-deficient mice. Our results thus
      suggest that ERK2 is required both for the proliferation of neural stem cells in
      the VZ during embryonic development and in the maintenance of NPC multipotency by
      suppressing the commitment of these cells to a glial lineage.

PMID- 18818437
TI  - Endogenous matrix metalloproteinase (MMP)-3 and MMP-9 promote the differentiation
      and migration of adult neural progenitor cells in response to chemokines.
AB  - Adult neurogenesis is regulated by both intrinsic programs and extrinsic stimuli.
      The enhanced proliferation of adult neural stem/progenitor cells (aNPCs) in the
      subventricular zone and the migration of neuroblasts toward the ischemic region
      in adult brains present a unique challenge as well as an opportunity to
      understand the molecular mechanisms underlying the extrinsic cue-induced
      neurogenic responses. Matrix metalloproteinases (MMPs) are a family of
      proteinases known to play a role in extracellular matrix remodeling and cell
      migration. However, their presence in aNPCs and their potential function in
      injury-induced aNPC migration remain largely unexplored. Here we demonstrate that
      in response to two injury-induced chemokines, stromal cell-derived factor 1 (SDF
      1) and vascular endothelial growth factor, aNPCs differentiated into migratory
      cells that expressed increased levels of MMP-3 and MMP-9. Whereas differentiated
      neuroblasts and a subpopulation of astrocytes migrated toward the chemokines,
      undifferentiated progenitors did not migrate. Blocking the expression of MMP-3 or
      MMP-9 in aNPCs interfered with both the differentiation of aNPCs and chemokine
      induced cell migration. Thus, endogenous MMPs expressed by aNPCs are important
      for mediating their neurogenic response to extrinsic signals.

PMID- 18818438
TI  - Human T-cell lymphotropic virus type 1 infection of CD34+ hematopoietic
      progenitor cells induces cell cycle arrest by modulation of p21(cip1/waf1) and
      survivin.
AB  - Human T-cell lymphotropic virus type 1 (HTLV-1) is an oncogenic retrovirus and
      the etiologic agent of adult T-cell leukemia (ATL), an aggressive CD4(+)
      malignancy. HTLV-2 is highly homologous to HTLV-1; however, infection with HTLV-2
      has not been associated with lymphoproliferative diseases. Although HTLV-1
      infection of CD4(+) lymphocytes induces cellular replication and transformation,
      infection of CD34(+) human hematopoietic progenitor cells (HPCs) strikingly
      results in G(0)/G(1) cell cycle arrest and suppression of in vitro clonogenic
      colony formation by induction of expression of the cdk inhibitor p21(cip1/waf1)
      (p21) and concurrent repression of survivin. Immature CD34(+)/CD38(-)
      hematopoietic stem cells (HSCs) were more susceptible to alterations of p21 and
      survivin expression as a result of HTLV-1 infection, in contrast to more mature
      CD34(+)/CD38(+) HPCs. Knockdown of p21 expression in HTLV-1-infected CD34(+) HPCs
      partially abrogated cell cycle arrest. Notably, HTLV-2, an HTLV strain that is
      not associated with leukemogenesis, does not significantly modulate p21 and
      survivin expression and does not suppress hematopoiesis from CD34(+) HPCs in
      vitro. We speculate that the remarkable differences in the activities displayed
      by CD34(+) HPCs following infection with HTLV-1 or HTLV-2 suggest that HTLV-1
      uniquely exploits cell cycle arrest mechanisms to establish a latent infection in
      hematopoietic progenitor/hematopoietic stem cells and initiates preleukemic
      events in these cells, which eventually results in the manifestation of ATL.

PMID- 18818439
TI  - IFATS collection: Human adipose-derived stem cells seeded on a silk fibroin
      chitosan scaffold enhance wound repair in a murine soft tissue injury model.
AB  - Soft tissue loss presents an ongoing challenge in reconstructive surgery. Local
      stem cell application has recently been suggested as a possible novel therapy. In
      the present study we evaluated the potential of a silk fibroin-chitosan (SFCS)
      scaffold serving as a delivery vehicle for human adipose-derived stem cells
      (ASCs) in a murine soft tissue injury model. Green fluorescent protein (GFP)
      labeled ASCs were seeded on SFCS scaffolds at a density of 1 x 10(5) ASCs per
      cm(2) for 48 hours and then suture-inlaid to a 6-mm, full-thickness skin defect
      in 6-week-old male athymic mice. Wound healing was tracked for 2 weeks by
      planimetry. Histology was evaluated at 2 and 4 weeks. Our data show that the
      extent of wound closure was significantly enhanced in the ASC-SFCS group versus
      SFCS and no-graft controls at postoperative day 8 (90% +/- 3% closure vs. 75% +/-
      11% and 55% +/- 17%, respectively). Microvessel density at wound bed biopsy sites
      from 2 weeks postoperative was significantly higher in the ASC-SFCS group versus
      SFCS alone (7.5 +/- 1.1 vs. 5.1 +/- 1.0 vessels per high-power field). Engrafted
      stem cells were positive for the fibroblastic marker heat shock protein 47,
      smooth muscle actin, and von Willebrand factor at both 2 and 4 weeks. GFP
      positive stem cells were also found to differentiate into epidermal epithelial
      cells at 4 weeks postoperative. In conclusion, human adipose-derived stem cells
      seeded on a silk fibroin-chitosan scaffold enhance wound healing and show
      differentiation into fibrovascular, endothelial, and epithelial components of
      restored tissue.

PMID- 18818440
TI  - Differential age trajectories of positive and negative affect: further evidence
      from the Berlin Aging Study.
AB  - In cross-sectional and longitudinal samples from the Berlin Aging Study, fellow
      researchers and I examined performance-based and self-evaluative indicators of
      functioning in two realms as predictors of individual differences and
      intraindividual changes in positive and negative affect. Cross-sectional and
      longitudinal structural equation models suggested that performance-based
      indicators (level of social involvement and test intelligence) were associated
      with positive affect, but not with negative affect. Evaluative indicators (self
      reported quality of social life and mental fitness) showed stronger relations to
      negative affect than to positive affect. The present evidence provides an
      explanation for the differential stability of positive versus negative affect in
      old age: Positive affect may decline because it requires objective competencies,
      which seem to decrease in old age. Negative affect may remain stable because it
      is associated with self-evaluations, which seem to change less with age.

PMID- 18818441
TI  - Death, dropout, and longitudinal measurements of cognitive change in old age.
AB  - During a 20-year longitudinal study of cognitive change in old age 2,342 of 5,842
      participants died and 3,204 dropped out. To study cognitive change as death
      approaches, we grouped participants by survival, death, dropout, or dropout
      followed by death. Linear mixed-effects pattern-mixture models compared rates of
      cognitive change before death and dropout from four quadrennial administrations
      of tests of fluid intelligence, vocabulary, and verbal learning. After we took
      into account the significant effects of age, gender, demographics, and
      recruitment cohorts, we found that approach to death and dropout caused
      strikingly similar reductions in mean test scores and amounts of practice gains
      between successive quadrennial testing sessions. Participants who neither dropped
      out nor died showed significant but slight cognitive declines. These analyses
      illustrate how neglect of dropout miscalculates effects of death, of worsening
      health, and of all other factors affecting rates of cognitive change.

PMID- 18818442
TI  - Ambulatory but sedentary: impact on cognition and the rest-activity rhythm in
      nursing home residents with dementia.
AB  - Physical activity has been positively associated with cognition and the rest
      activity rhythm. In the present study, nursing staff classified ambulatory
      nursing home residents with moderate dementia either as active (n=42) or as
      sedentary (n=34). We assessed the rest-activity rhythm by means of actigraphy,
      and we administered neuropsychological tests to assess cognitive functioning.
      Compared with the group that was considered sedentary, the group that was
      considered active had a significantly better rest-activity rhythm, indicating
      agreement between nursing staff classifications and data gathered by the
      actigraph. Cognitive function was related neither to active-sedentary
      classification nor to actigraph measures. Similar ambulatory nursing home
      residents with dementia may show considerable differences in their level of daily
      physical activity and in their rest-activity rhythm, but the precise relationship
      among all variables requires further investigation.

PMID- 18818443
TI  - Acetylcholinesterase inhibitor in combination with cognitive training in older
      adults.
AB  - To determine if donepezil, an acetylcholinesterase (AChE) inhibitor, improved the
      assimilation of cognitive training by older adults with memory complaints, we
      gave 168 nondemented, community-dwelling volunteers with memory complaints either
      5 mg of donepezil (Aricept) or placebo daily for 6 weeks in a randomized, double
      blind, placebo-controlled trial. The dosage rose to 10 mg daily for another 6
      weeks before a 2-week course of cognitive training and was maintained for the
      remainder of a year. Cognitive training improved performance; donepezil was well
      tolerated. However, there were no significant benefits of donepezil compared with
      placebo. An additional dose-ranging study with a starting dose of 5 mg a day
      suggests that the high dose was not the reason. Physiological tolerance may occur
      with chronic donepezil treatment and may increase AChE levels; this may be why
      short-term studies have shown the benefit of AChE inhibitor use in nondemented
      participants whereas chronic use has failed to enhance cognition.

PMID- 18818444
TI  - Effects of sensorimotor adaptation training on functional mobility in older
      adults.
AB  - The goal of this study was to determine if prolonged exposure to perceptual-motor
      mismatch increased adaptability and retention of balance in older adults. Sixteen
      adults, aged 66 to 81 years, were randomized to one of two groups: either the
      control group (n=8) or the experimental group (n=8). Both groups first completed
      six trials of walking an obstacle course. Participants then trained twice a week
      for 4 weeks. In the training, the control group walked on a treadmill for 20
      minutes while viewing a static visual scene and the experimental group walked on
      a treadmill for 20 minutes while viewing a rotating visual scene that provided a
      perceptual-motor mismatch. Following training, both groups were post-tested on
      the obstacle course. The experimental group moved faster through the obstacle
      course with fewer penalties. This training effect was retained for 4 weeks.
      Exposure to perceptual-motor mismatch induced an adaptive training effect that
      improved balance and locomotor control in older adults.

PMID- 18818445
TI  - Are comparisons the answer to understanding behavioral aspects of aging in racial
      and ethnic groups?
AB  - The knowledge gained from studying diverse populations should help to address
      inequities and prepare us to deal with the needs of the increasing number of
      older minorities in this country. At the same time, research that is not properly
      conducted threatens to lead us astray and misconstrue relationships and outcomes
      related to behavioral aspects of aging. In this article, we propose that simple
      comparisons between groups are neither necessary nor sufficient to advance our
      understanding of ethnic minorities. We discuss common pitfalls conducted in group
      differences research, including a specific treatment on the issue of statistical
      power issues. Our goal is to encourage the use of multiple methodological designs
      in the study of issues related to racial and ethnic minorities by demonstrating
      some of the advantages of lesser employed approaches.

PMID- 18818446
TI  - Longitudinal relationships between cognitive functioning and depressive symptoms
      among Hispanic older adults.
AB  - This study examines the relationship between cognitive functioning and depressive
      symptoms across 3 years in a prospective study of 273 community-dwelling,
      Hispanic older adults in Miami. The analyses extend the literature by testing for
      a bidirectional or reciprocal relationship between depressive symptoms and
      cognitive functioning over time and by examining the relationship between these
      variables among Hispanics, an understudied population at risk of developing
      depressive symptoms and cognitive impairments. Structural equation modeling with
      a cross-lagged panel design showed that depressive symptoms were unrelated to
      subsequent cognitive functioning. However, cognitive functioning was related to
      subsequent depressive symptoms at every time point, such that poorer cognitive
      functioning was related to higher depressive symptoms. Findings suggest that
      cognitive declines may predict depressive symptoms in community-dwelling Hispanic
      older adults.

PMID- 18818447
TI  - Cohort changes in active life expectancy in the U.S. elderly population:
      experience from the 1982-2004 National Long-Term Care Survey.
AB  - OBJECTIVES: To understand declines in chronic disability prevalence in the U.S.
      elderly population, we examined cohort changes in active life expectancy, a
      health measure relating population disability and longevity dynamics. METHODS: We
      computed active life expectancy and life expectancy using the six National Long
      Term Care Surveys done from 1982 to 2004 and linked to continuous-time Medicare
      service data for the same time period by using a stochastic process model based
      on disability scores calculated using grade of membership analyses. We
      simultaneously estimated continuous-time disability dynamic and mortality
      functions to calculate life tables for specific disability states and for
      temporally changing mixtures of disability states. RESULTS: Disability dynamics,
      measured as changes in grade of membership scores, showed significant variation
      across two birth cohorts followed for 24 years. Disability dynamics and
      disability-specific hazard functions were significantly improved in the younger
      cohort (persons aged 65-74 in 1982). DISCUSSION: Our results, supporting the
      hypothesis of morbidity compression, indicate that younger cohorts of elderly
      persons are living longer in better health. The methods describe individual
      disability transitions and mortality and other factors associated with disability
      changes, making it possible to better evaluate interventions to promote future
      declines in disability.

PMID- 18818449
TI  - Religious participation and mortality risk among the oldest old in China.
AB  - OBJECTIVE: Rapid population aging in China calls for more research into social
      factors responsible for health and well-being among older adults. This article
      adds to this line of inquiry by examining the relationship between religious
      participation and mortality, as well as the potential pathways linking these
      factors and subgroup variations among oldest old Chinese. METHODS: Using two
      waves (1998 and 2000) of the Chinese Longitudinal Healthy Longevity Survey, I
      estimated Cox proportional hazards models for a nationwide sample of Chinese aged
      80 to 105. RESULT: Controlling for a wide range of covariates, I found religious
      participation to be significantly associated with lower risk of mortality for
      oldest old women and for individuals in poor health. Engaging in leisure
      activities and exercises partially accounted for this association. DISCUSSION:
      Findings suggest that (a) religious participation, associated with other socially
      integrated and cognitively stimulating activities, predicts mortality risk among
      oldest old Chinese; and (b) religious participation offers psychosocial resources
      that are likely to compensate for the increased mortality risk associated with
      disadvantaged socioeconomic conditions of certain vulnerable groups such as women
      and individuals in poor health.

PMID- 18818448
TI  - Gender differences in functional status in middle and older age: are there any
      age variations?
AB  - OBJECTIVES: The present study examines gender differences in changes in
      functional status after age 50 and how such differences vary across different age
      groups. METHODS: Data came from the Health and Retirement Study, involving up to
      six repeated observations of a national sample of Americans older than 50 years
      of age between 1995 and 2006. We employed hierarchical linear models with time
      varying covariates in depicting temporal variations in functional status between
      men and women. RESULTS: As a quadratic function, the worsening of functional
      status was more accelerated in terms of the intercept and rate of change among
      women and those in older age groups. In addition, gender differences in the level
      of functional impairment were more substantial in older persons than in younger
      individuals, although differences in the rate of change between men and women
      remained constant across age groups. DISCUSSION: A life course perspective can
      lead to new insights regarding gender variations in health within the context of
      intrapersonal and interpersonal differences. Smaller gender differences in the
      level of functional impairment in the younger groups may reflect improvement of
      women's socioeconomic status, greater rate of increase in chronic diseases among
      men, and less debilitating effects of diseases.

PMID- 18818450
TI  - Social integration and social support among older adults following driving
      cessation.
AB  - OBJECTIVES: The objective of this study was to evaluate the impact of driving
      cessation on social integration and perceived support from relatives and friends
      among older adults. METHODS: Data came from the population-based Baltimore
      Epidemiologic Catchment Area Study. We restricted analyses to participants aged
      60+ with a history of driving (n=398). Social integration (number and frequency
      of contact) and perceived social support from relatives/friends, driving status
      (continuing or ceased), and demographic and health characteristics were assessed
      at interviews 13 years apart. The potential mediating role of ability to use
      public transit was also investigated. We used repeated measures random-intercept
      models to evaluate the effect of driving cessation on social network
      characteristics over time. RESULTS: Former drivers were older, were more likely
      to be female and non-White, had lower education, had poorer self-rated health,
      and had lower Mini-Mental State Examination scores relative to continuing
      drivers. Over the follow-up period, cessation was associated with reduced network
      of friends (odds ratio=0.49, p<.05). This association was not mediated by ability
      to use public transportation. Cessation had no impact on support from friends or
      relatives. DISCUSSION: Social integration is negatively affected by driving
      cessation even among elders who feel competent in using alternative forms of
      transportation, at least concerning networks of friends.

PMID- 18818451
TI  - Preventive health behaviors among grandmothers raising grandchildren.
AB  - OBJECTIVES: We examined differential preventive health behavior among
      grandmothers who recently began raising a grandchild, grandmothers raising a
      grandchild for at least 2 years, and grandmothers not raising a grandchild.
      METHODS: Data came from the 2000, 2002, and 2004 waves of the Health and
      Retirement Study. We ran multivariate logistic regression models to assess
      receipt of influenza vaccination, cholesterol screening, monthly breast self
      exam, mammography, and Papanicolaou (Pap) tests among grandmothers aged 50 to 75.
      RESULTS: Grandmothers who recently began raising a grandchild were significantly
      less likely to report influenza vaccination and cholesterol screening than
      grandmothers not raising grandchildren, even after we controlled for increased
      emotional and financial strains within the household. We also observed this
      association for Pap tests, although this finding was only marginally significant.
      Grandmothers who had been raising a grandchild for at least 2 years were
      significantly more likely to report influenza vaccination and monthly breast self
      exam than grandmothers not raising grandchildren. DISCUSSION: The enhancement of
      preventive behavior seen among long-term grandparent caregivers does not fully
      offset the suppression of preventive behavior during the transition into care;
      support groups should target a range of interventions toward the promotion of
      healthy behavior among new grandparent caregivers.

PMID- 18818452
TI  - The meaning and significance of self-management among socioeconomically
      vulnerable older adults.
AB  - OBJECTIVES: The aim of this study was to describe and contrast perceptions of
      self-management among socioeconomically vulnerable and nonvulnerable older
      adults. METHODS: We used in-depth, in-home interviews guided by identity theory.
      Analyses included reviewing audiotapes, creating and comparing field notes,
      coding transcripts, and identifying themes based on case summaries. Interviews
      took place in patients' homes. Participants were 23 vulnerable older adults with
      incomes at or below 200% of the federal poverty level and no private insurance
      and 12 older adults with private health insurance. RESULTS: The vulnerable sample
      had lower educational attainment and lower health literacy than the privately
      insured sample. Keeping doctor visits and taking prescription medications largely
      defined self-management for the vulnerable sample but were just two of a number
      of roles noted by the privately insured group, who expressed health promotion as
      the key to healthy aging. The vulnerable interviewees relayed few examples of
      healthy aging and did not have expectations for healthful aging. In contrast, the
      privately insured interviewees gave examples and had expectations of living long
      and healthfully into old age. DISCUSSION: Improved understanding of the role of
      social context in expectations regarding aging, and awareness of and priorities
      for self-management, could lead to improvements in self-management support and
      thus chronic care outcomes.

PMID- 18818453
TI  - Racial differences in arthritis-related stress, chronic life stress, and
      depressive symptoms among women with arthritis: a contextual perspective.
AB  - OBJECTIVES: This study examined the effects of arthritis-related stress and
      chronic life stress on depressive symptoms among African Americans and Whites
      with arthritis. METHODS: Participants included 175 African American and White
      women (aged 45-90) who completed structured questionnaires assessing arthritis
      related stress (i.e., pain, functional impairment, perceived stress), chronic
      life stress (i.e., discrimination, financial stress, life stressors), and well
      being (i.e., depressive symptoms). RESULTS: African Americans reported more
      functional impairment and lower perceived arthritis stress, but more life
      stressors, financial stress, and discrimination, than Whites. Arthritis-related
      stress accounted for similar proportions of variance in depressive symptoms
      across African Americans (DeltaR2=.16, p<.001) and Whites (DeltaR2=.24, p<.001).
      However, chronic life stressors explained significantly more variance among
      African Americans (DeltaR2=.20, p<.001, vs DeltaR2=.06, p<.05). DISCUSSION:
      Findings demonstrate the importance of considering contextual factors influencing
      women's health and well-being, particularly for those women with a chronic
      illness, including arthritis. Although arthritis-related stressors may be the
      predominant factors affecting well-being for Whites with arthritis, well-being in
      African Americans with arthritis is also closely tied to broader life stressors.
      Results suggest the importance of looking beyond illness-specific stressors when
      studying aging and health.

PMID- 18818454
TI  - Racial and ethnic disparities in the treatment of dementia among Medicare
      beneficiaries.
AB  - OBJECTIVES: Numerous studies have documented disparities in health care
      utilization between non-Hispanic White and minority elders. We investigated
      differences in anti-dementia medication use between non-Hispanic White and
      minority community-dwelling Medicare beneficiaries with dementia. METHODS: Using
      multivariate analysis with generalized estimating equations, we estimated
      prevalence ratios (PRs) for anti-dementia medication use by race/ethnicity for
      1,120 beneficiaries with dementia from years 2001 through 2003 of the Medicare
      Current Beneficiary Survey. RESULTS: After adjusting for demographics,
      socioeconomics, health care access and utilization, comorbidities, and service
      year, we found that anti-dementia medication use was approximately 30% higher
      among non-Hispanic Whites compared to other racial/ethnic groups (PR=0.73, 95%
      confidence interval [CI]=0.59, 0.91). As for individual racial/ethnic groups,
      prevalence disparities remained significant for non-Hispanic Blacks (PR=0.75, 95%
      CI=0.57, 0.99) and non-Hispanic others (PR=0.50, 95% CI=0.26, 0.96) but were
      attenuated for Hispanics (PR=0.84, 95% CI=0.59, 1.20). DISCUSSION: Results
      provide evidence that racial/ethnic disparities in utilization of drugs used to
      treat dementia exist and are not accounted for by differences in demographic,
      economic, health status, or health utilization factors. Findings provide a
      foundation for further research that should use larger numbers of minority
      patients and consider dementia type and severity, access to specialty dementia
      care, and cultural factors.

PMID- 18818455
TI  - Letter by Kounis et al regarding article, "sirolimus-eluting stents suppress
      neointimal formation irrespective of metallic allergy".

PMID- 18818457
TI  - Influence of nonsteroidal anti-inflammatory drugs on osseointegration.
AB  - This paper reviews contemporary literature concerning the possible influence of
      nonsteroidal anti-inflammatory drugs (NSAIDs) on osseointegration. In vitro
      studies concerning the effect of NSAIDs on growth factors and bone-generating
      cells are the primary source of data pertaining to this issue because relatively
      few in vivo studies have been conducted. It is concluded that prescribing NSAIDs
      during the early postoperative period is likely not without negative effect,
      although any negative influence appears to be temporary and does not affect the
      final outcome of osseointegration.

PMID- 18818458
TI  - Prostaglandins and bone: potential risks and benefits related to the use of
      nonsteroidal anti-inflammatory drugs in clinical dentistry.
AB  - In the skeleton, prostaglandins, mainly PGE(2) produced by osteoblasts under COX
      2 stimulation, play either a stimulatory or an inhibitory role in bone
      metabolism, depending on the physiological or pathological conditions. The
      anabolic effect occurs largely in response to mechanical forces and in bone
      fracture healing, whereas PGE(2)-mediated resorption contributes significantly to
      bone loss in inflammatory diseases and in response to prolonged immobilization.
      Many reports have shown that conventional nonsteroidal anti-inflammatory drugs
      (NSAIDs) may delay fracture healing and negatively interfere with spinal fusion
      in both humans and other animals, whereas the alleged inhibitory effects of COX-2
      selective NSAIDs still lacks experimental and clinical evidence. Pertaining to
      clinical dentistry, recent studies have suggested a potential adjuvant role for
      NSAIDs in periodontal therapy. There are few experimental reports addressing the
      deleterious effects of conventional NSAIDs on alveolar bone healing; clinical
      reports, relating mostly to short-term administration of NSAIDs for management of
      post-extraction edema and pain, are just as rare and have noted no clinically
      perceptible delay in bone healing. Additional studies are necessary in order to
      elucidate whether patients who require reparational bone formation can safely
      receive prolonged treatment with NSAIDs, and which drug types are less harmful.

PMID- 18818459
TI  - Short-term effects of oral appliances with equal bite-raising distance but with
      varying protrusions on occlusal force, contact area and load center.
AB  - The purpose of this study was to demonstrate how short-term wearing of an oral
      appliance (OA) with equal bite-raising distance but with varying protrusions
      affects occlusal force, contact area and load center. Twelve young healthy
      volunteers participated. With the appliance, the mandible was protruded 0%, 45%,
      60% and 75% of maximum protrusion capacity, with 10 mm bite-raising between the
      first molars. The occlusal force, contact area and load center at maximum
      voluntary clenching were measured before wearing the OA, at 1 h, 3 h and 6 h
      during wearing, and 1 h after removal. When compared to the values before wearing
      the OA, occlusal force was significantly lower at 1 h, 3 h and 6 h during wearing
      in the case of no mandibular protrusion, and at 3 h and 6 h after for 45%, 60%
      and 75% of maximum mandibular protrusion (P < 0.05). Occlusal contact area was
      significantly smaller at 1 h and 6 h during wearing in the case of no protrusion,
      and at 6 h during wearing in the case of 45% of maximum protrusion (P < 0.05).
      There was a tendency for anterior shift in the location of the occlusal load
      center at 3 h and 6 h during wearing of the OA with any level of maximum
      protrusion. No significant change in these three measurements was found at 1 h
      after removal of the OA. The present study demonstrated that wearing an OA had
      only a marginal and transient influence on oral functions when their changes were
      compared before and after wearing the OA.

PMID- 18818460
TI  - A double-blind randomized clinical trial of subgingival minocycline for chronic
      periodontitis.
AB  - The purpose of this study was to evaluate the presence of A.
      actinomycetemcomitans, P. gingivalis, P. intermedia, E. corrodens and F.
      nucleatum in 30 subjects with chronic periodontitis treated by scaling and root
      planing (SRP) plus minocycline (test group) during 12 months with regular
      trimester maintenance care. Additionally, we evaluated whether the beneficial
      effects of the therapy on the microbial flora persisted for 24 months. The test
      group (n = 15) and the control group [SRP plus placebo (n = 15)] were randomly
      assigned. After SRP, subjects received minocycline or placebo at the baseline,
      and at 3, 6, and 9 months at all sites with a periodontal pocket depth (PD) of
      >or= 6 mm. Moreover, two homologous teeth, initially PD >or= 6 mm, were
      clinically and microbially monitored by PCR at the baseline, and at 3, 6, 9, 12
      and 24 months. Differences in mean PD values between groups were analyzed by
      Student's t-test (P < 0.05). The results for bacterial frequencies showed no
      significant differences between groups (Fisher's Exact test, P < 0.05) or between
      time-points (Friedman test, P < 0.05). We failed to detect any differences
      between groups related to the presence of target pathogens for 12 months. The
      effects of both therapies on the microbial flora did not persist for 24 months.
      The group without supportive periodontal therapy showed an improvement in the
      pattern of pathogens with either of the therapies.

PMID- 18818461
TI  - Self reported dental health attitude and behavior of dental students in India.
AB  - The aim of the present study was to evaluate the oral health attitudes and
      behavior of undergraduate dental students in India according to age, sex and
      level of dental education, and to compare it with those of other countries with
      different socioeconomic conditions. A self-administered questionnaire based on
      the Hiroshima University - Dental Behavior Inventory (HU-DBI) was distributed
      among 372 dental students at Darshan Dental College and Hospital (DDCH). The
      response rate was 75.8% with 44% males and 56% females. The mean HU-DBI score
      showed a significant relationship (P < 0.05) with age by one way-analysis of
      variance (ANOVA). The students were considerably concerned about the appearance
      of their teeth and gums and halitosis. The total mean score was not markedly
      higher in the clinical years (years 3 and 4) than in the non-clinical years
      (years 1 and 2), indicating that the students were almost equally aware. Although
      there were no statistically significant differences in gender and academic year
      for the mean score of HU-DBI, the present study showed that dental students in
      India generally had poorer oral health awareness compared to several other
      countries. The oral health behavior of Indian dental students has to be improved
      in order to serve as a positive model for their patients, family, and friends.

PMID- 18818462
TI  - Comparison of microleakage with three different thicknesses of mineral trioxide
      aggregate as root-end filling material.
AB  - The aim of this study was to compare the microleakage at three different
      thicknesses of mineral trioxide aggregate (MTA) as a root-end filling material.
      Ninety extracted human maxillary incisor teeth were selected and the root canals
      of the teeth were cleaned, shaped and obturated with gutta percha and AH-plus
      sealer. Teeth were randomly divided into 3 groups each containing 20 experimental
      samples, and 5 positive and 5 negative controls. In the first, second and third
      experimental groups, cavities of 1 mm, 2 mm and 3 mm in depth, respectively, were
      prepared and filled with MTA. Leakage was determined by the dye penetration
      method using India ink, and a stereomicroscope at x16 magnifications and 0.1 mm
      accuracy. The microleakage in the 3-mm and 2-mm root-end cavities was less than
      at 1 mm depth, but analysis of variance revealed no significant differences among
      the three different thicknesses.

PMID- 18818463
TI  - Ability of nanocrystalline hydroxyapatite paste to promote human periodontal
      ligament cell proliferation.
AB  - Recent studies indicate that nanocrystalline hydroxyapatite (nano-HA) paste
      represents a promising class of bone graft substitute. However, the underlying
      molecular mechanisms of nano-HA function have not yet been determined. This study
      was conducted to investigate the proliferation of human periodontal ligament
      (PDL) cells cultured in the presence of nano-HA paste and to characterize
      associated changes in intracellular signaling pathways. Cultured PDL cells were
      stimulated with nano-HA paste and enamel matrix derivative (EMD) in a soluble
      form. Proliferation of PDL cells was determined by incorporation of
      bromodeoxyuridine (BrdU) in the DNA of proliferating cells. In order to
      understand the signaling mechanisms underlying the increased cell proliferation
      of PDL cells exposed to nano-HA, the phosphorylation status of the
      serine/threonine protein kinase Akt, of the signal regulated kinases ERK 1/2 and
      of the epidermal growth factor receptor (EGFR) was analyzed by Western blotting
      using phospho-specific antibodies. Nano-HA paste showed two-fold less
      proliferation potential than EMD, but both substrates increased the proliferation
      rate significantly (P < 0.05) as compared with the negative control. The
      increased proliferation rate of PDL cells in the presence of nano-HA paste was
      mechanistically linked to activation of the epidermal growth factor receptor
      (EGFR) and its downstream targets ERK1/2 and Akt. In conclusion, our findings
      suggest that nano-HA paste is a stimulator of cell proliferation, possibly
      contributing to the main processes of periodontal tissue regeneration.

PMID- 18818464
TI  - Mesiodens: a radiographic study in children.
AB  - We analyzed the frequency and radiological features of mesiodens in a group of
      children in Turkey. The study was based on a radiographic review of 23,000
      pediatric patients (male: 12,667 female; 10,333) who visited the Department of
      Oral Diagnosis and Radiology during the period 2003-2005 (3 years). The presence
      of an unerupted supernumerary tooth, or tooth bud between the 2 central incisors
      or as unilateral or bilateral teeth in the midline of the maxilla was noted as
      mesiodens on radiographs. Eighty-five cases of mesiodens in 69 patients were
      found. Complete documentation, including radiographs, for these 69 patients were
      studied and analyzed. In addition to gender and age, the following information
      about the mesiodens was recorded: 1) number; 2) shape; 3) position; 4)
      complications caused by the mesiodens; 5) treatment. Of the 69 patients, the
      ratio of boys (47 cases) to girls (22 cases) was 2.1:1. Fifty-three (76.8%) of
      the children had 1 mesiodens, and 16 (23.1%) had 2 mesiodentes bilaterally to the
      midline. Of the 85 mesiodentes, 67 (78.8%) were fully impacted, 6 (7%) were
      partially erupted, and 12 (14.1%) were fully erupted. Most of the mesiodentes
      (55.2%) were found in the vertical position, followed by inverted position
      (37.6%), and horizontal position (7%). The main complications were delayed
      eruption of the permanent incisors (38.8%), maxillary midline diastema (17.6%),
      axial rotation or inclination of erupted permanent incisors (16.4%), and
      resorption of the adjacent teeth (4.7%) The prevelance of mesiodens has been
      estimated to be 0.15% to 2.2% of the population.

PMID- 18818465
TI  - Relationship between the inclination of the coronoid process of the mandible and
      the electromyographic activity of the temporal muscle in skeletal Class I and II
      individuals.
AB  - The aim of this study was to verify the relationship between the inclination of
      the coronoid process of the mandible, and electromyographic activity of the
      anterior part of the temporal muscle in skeletal Class I and II individuals.
      Forty-seven volunteers (mean age 24.5 +/- 3.9 years) were subdivided into two
      groups, according to angle ANB: Class I (n = 25) and II (n = 22). Two
      radiographic examinations were performed; one lateral cephalogram to measure
      angle ANB, and one frontal cephalogram to measure the inclination of the coronoid
      process. Electromyographic (EMG) examination of the anterior part of the
      subjects' temporal muscles was performed. Statistical analysis of the data showed
      that Class II individuals presented lower electromyographic activity of the
      anterior part of the temporal muscle. Based on the results obtained, it was
      concluded that the skeletal classes analyzed had no influence on the inclination
      of the coronoid process. The inclination of the coronoid process was not
      influenced by the electromyographic activity of the anterior part of the temporal
      muscle in Class I and II individuals; however, the lower electromyographic
      activity of the anterior part of the temporal muscle could be influenced by the
      skeletal class in Class II individuals.

PMID- 18818466
TI  - Anorganic bovine bone and a silicate-based synthetic bone activate different
      microRNAs.
AB  - Bio-Oss (BO), composed of anorganic bovine bone, is widely used in several bone
      regeneration procedures in oral surgery. PerioGlas (PG) is an alloplastic
      material that has been used for grafting of periodontal osseous defects since the
      1990s. However, how these biomaterials alter osteoblast activity to promote bone
      formation is poorly understood. We attempted to address this question by using
      microRNA microarray techniques to investigate differences in translational
      regulation in osteoblasts exposed to BO and PG. By using miRNA microarrays
      containing 329 probes designed from human miRNA sequences, we investigated miRNAs
      whose expression was significantly modified in an osteoblast-like cell line (MG
      63) cultured with BO vs PG. Three up-regulated miRNAs (mir-337, mir-200b, mir
      377) and 4 down-regulated miRNAs (mir-130a, mir-214, mir-27a, mir-93) were
      identified. Our results indicated that BO and PG act on different miRNAs.
      Globally, PG causes activation of bone-forming signaling, whereas BO also
      activates cartilage-related pathways.

PMID- 18818467
TI  - In vitro evaluation of the antimicrobial activity of a new resin-based endodontic
      sealer against endodontic pathogens.
AB  - The purpose of this study was to compare the antimicrobial activities of a new
      resin-based SuperBond (SB) Sealer and five other sealers/cements against
      endodontic pathogens. The antimicrobial activities of SB Sealer, Sealapex, AH
      plus, Roeko Seal Automix, Canals N, and ProRoot mineral trioxide aggregate (MTA)
      were examined using a double-layered method. The microorganisms Staphylococcus
      aureus, Enterococcus faecalis, Candida albicans, Streptococcus mutans, and
      Streptococcus sanguinis were used. Live microorganisms were stained using
      triphenyltetrazolium chloride, and the zones of inhibition of microorganism
      growth were measured. The antimicrobial activity of SB Sealer was significantly
      lower than that of the other sealers, except for Pro Root MTA, against S. aureus,
      C. albicans, S. mutans, and S. sanguinis, but no activity against E. faecalis was
      detected. On the other hand, AH plus exhibited the highest antimicrobial
      activity. Pro Root MTA showed no antimicrobial activity against any of the
      microorganisms tested. SB Sealer offered no antimicrobial advantage over the
      other sealers tested except for Pro Root MTA.

PMID- 18818468
TI  - Degree of conversion and plasticization of dimethacrylate-based polymeric
      matrices: influence of light-curing mode.
AB  - This study analyzed the correlation between the degree of conversion (DC) and the
      plasticization (P) of experimental dimethacrylate-based polymeric matrices. Six
      polymeric matrices produced with Bis-GMA (G), UDMA (U) and TEGDMA (T)
      dimethacrylate monomers were studied: G, U, GT55, GT73, GU55, GU73 - (55 =
      50/50wt% and 73 = 70/30wt%). Photoactivation was induced by camphoroquinone/ethyl
      N, N-dimethyl-4-aminobenzoate. The matrices were light-cured using two modes:
      Standard (S) - 850 mW/cm(2) for 20 s, and Gradual (G) - 100 up to 1000 mW/cm(2)
      for 10 s + 1,000 mW/cm(2) for 10 s. The degree of conversion (%) was obtained by
      using a FT-IR spectrometer equipped with an attenuated total reflectance crystal
      (ATR), and plasticization was estimated by the softening effect of ethanol. No
      correlation was found between the degree of conversion and plasticization (r =
      0.32 / P = 82.35 +/- 0.85DC). The means of DC% were: GT55 (66.18 +/- 3.29) > U
      (59.34 +/- 5.61) > GT73 (54.97 +/- 7.89) > GU55 (50.60 +/-6.26) > GU73 (44.02 +/-
      4.85) > G (38.25 +/- 3.35), (P < 0.05). The matrices with TEGDMA showed the
      highest plasticization. The light-curing mode influenced only G > S
      plasticization (P < 0.05).

PMID- 18818469
TI  - Antibacterial effects of three experimental quaternary ammonium salt (QAS)
      monomers on bacteria associated with oral infections.
AB  - The aim of this study was to test the antibacterial effects of three experimental
      quaternary ammonium salt monomers in order to evaluate their potential
      applications as dental materials. In vitro susceptibility testing of the monomers
      was performed by the broth dilution method on bacteria associated with oral
      infections: Streptococcus mutans ATCC 25175, Actinomyces viscosus ATCC 15987,
      Staphylococcus aureus ATCC 29213 and Lactobacillus casei ATCC 393. The time-kill
      kinetics of the monomer with relatively higher antibacterial activity against S.
      mutans were also investigated. It was found that all the tested bacteria strains
      were susceptible to the three monomers, among which methacryloxylethyl cetyl
      ammonium chloride (DMAE-CB) exhibited the lowest minimal inhibitory
      concentrations, ranging from 1.2 to 4.8 microg/ml. The time-kill curve showed
      that DMAE-CB achieved 99.44% killing at 19.2 microg/ml (4 times the minimal
      bactericidal concentration) against S. mutans after 1 min and 100% killing within
      10 min of contact. This result indicates that the quaternary ammonium salt
      monomer DMAE-CB may be a candidate antibacterial agent for incorporation into
      dental restorative materials.

PMID- 18818470
TI  - Bond strength to bovine dentin of a composite core build-up material combined
      with four different bonding agents.
AB  - Clearfil DC Bond (DC) is a new single-step, dual-cure bonding agent. In this
      study, the shear bond strengths of a core build-up composite to dentin used with
      four bonding systems [DC, Unifil Core Self-Etching Bond (UC), Clearfil SE Bond
      (SE) and Cleafil tri-S Bond (TS)] were measured. The bonding ability after 7 days
      of storage and in vitro durability following 20,000 thermocycles were also
      evaluated. The bond strength of DC did not differ significantly from those of
      other bonding systems after 24 hours of storage. Another dual-cure bonding
      system, UC, showed a significant reduction of bond strength after 7 days of
      storage. On the other hand, the bond strength of TS, a light-cured bonding system
      with a similar composition to DC, was reduced significantly following 20,000
      thermocycles. SE, a two-step light-cure bonding system in the same series as DC,
      provided superior bond strength under all conditions. Although DC showed a
      slightly lower bond strength than SE, there was no significant difference between
      DC and SE under all conditions. Consequently, DC may be a useful and effective
      bonding system for multiple composite resin restorations.

PMID- 18818471
TI  - Evaluation of oral mucosa epithelium in type II diabetic patients by an
      exfoliative cytology method.
AB  - Diabetes mellitus is a common metabolic disease that causes chronic hyperglycemia
      and disturbances in carbohydrate, lipid, and protein metabolism. Although
      diabetes can cause considerable cellular changes, this field has attracted little
      research. We therefore decided to evaluate the quantitative and qualitative
      changes in oral epithelial cells using an exfoliative cytology method. In 30
      control individuals and 30 patients with type II diabetes, smears were obtained
      from two distinct oral sites: the buccal mucosa and tongue dorsum. The oral
      smears were stained using Papanicolaou solution. Quantitative and qualitative
      changes were evaluated in each slide. For this purpose, 50 clearly defined cells
      in each slide were microscopically evaluated, and photographs were subjected to
      computerized morphometric analysis. Cytoplasmic and nuclear areas in the diabetic
      group were significantly higher than in the control group. The
      cytoplasmic/nuclear ratio was lower in the control group. At both smear sites,
      the proportion of cells with nuclear changes was higher in the diabetic group.
      Diabetes mellitus can cause alterations in the oral epithelium that are
      detectable with this exfoliative cytology method. The method may be viable in
      evaluating this disease.

PMID- 18818472
TI  - Dental education in Peru.
AB  - This paper provides information about Peru's dental history and dental school
      system, including the curriculum and dental licensure. With the increase in the
      number of dental schools in Peru, the number of dentists is also increasing.
      Until 1965, Peru had only three dental schools; currently, there are 14. Four of
      these dental schools are public, and ten are private. A five- or six-year dental
      program leads to the B.D.S. degree. After successful completion of a thesis
      defense or competency examination, the D.D.S. degree is awarded. The D.D.S. is
      mandatory for practicing dentistry in Peru. Currently, there are approximately
      14,000 active dentists, with a dentist-patient ratio of approximately 1:2,000.

PMID- 18818473
TI  - Keratocystic odontogenic tumor invading the right maxillary sinus: a case report.
AB  - Keratocystic odontogenic tumor (KCOT) is a benign intraosseous neoplasm of the
      jaw. Involvement of the maxillary sinus is an unusual presentation. We present
      the case of a 23-year-old man with extensive KCOT and impacted third molar in the
      right maxillary sinus. The clinical, radiological, and histological features of
      this tumor and its surgical management are discussed.

PMID- 18818474
TI  - Removal of broken dental needle using mobile digital C-arm.
AB  - Breakage of needles is one of the most frustrating and distressing complications
      of local anesthesia. It is also one of the easiest to prevent. This article
      describes the use of the C-arm digital fluoroscope for retrival of a broken
      dental needle from the pterygomandibular space.

PMID- 18818475
TI  - Use of mineral trioxide aggregate in the open apex of a maxillary first premolar.
AB  - Mineral trioxide aggregate (MTA) has shown potential as a root-end filling
      material. This clinical case describes the successful treatment of a premolar
      with an open apex using MTA and the warm gutta-percha technique. The results
      suggested that MTA may be used as an apical filling material in permanent teeth
      with multiple canals.

PMID- 18818476
TI  - Oral pemphigus vulgaris: a case report with review of the literature.
AB  - Pemphigus vulgaris is a chronic autoimmune mucocutaneous disease that initially
      manifests in the form of intraoral lesions, which spread to other mucous
      membranes and the skin. The etiology of pemphigus vulgaris is still unknown,
      although the disease has attracted considerable interest. The pemphigus group of
      diseases is characterized by the production of autoantibodies against
      intercellular substances and is thus classified as autoimmune diseases. Most
      patients are initially misdiagnosed and improperly treated for many months or
      even years. Dental professionals must be sufficiently familiar with the clinical
      manifestations of pemphigus vulgaris to ensure early diagnosis and treatment,
      since this in turn determines the prognosis and course of the disease. Here, we
      report a case of pemphigus vulgaris that was misdiagnosed in its earliest stage.

PMID- 18818477
TI  - A mandibular second premolar with three canals and atypical orifices.
AB  - Mandibular second premolars with three canals (Type V, Vertucci) and separate
      foramina are very rare. The anatomy of the pulp chamber floor in these premolars
      usually reveals one lingual and two buccal orifices at the same level. This case
      report describes a second premolar with three canals and an unusual pulpal floor
      anatomy with one distobuccal and one distolingual orifice at the same level and
      an orifice on the mesiolingual wall. Very careful examination of the pulpal
      space, preferably with an optical device, is recommended to locate any unusual
      orifices.

PMID- 18818478
TI  - Pentadecapeptide BPC 157, in clinical trials as a therapy for inflammatory bowel
      disease (PL14736), is effective in the healing of colocutaneous fistulas in rats:
      role of the nitric oxide-system.
AB  - We focused on the therapeutic effect of the stable gastric pentadecapeptide BPC
      157 and how its action is related to nitric oxide (NO) in persistent
      colocutaneous fistula in rats (at 5 cm from anus, colon defect of 5 mm, skin
      defect of 5 mm); this peptide has been shown to be safe in clinical trials for
      inflammatory bowel disease (PL14736) and safe for intestinal anstomosis therapy.
      BPC 157 (10 microg/kg, 10 ng/kg) was applied i) in drinking water until the
      animals were sacrificed at post-operative day 1, 3, 5, 7, 14, 21, and 28; or ii)
      once daily intraperitoneally (first application 30 min following surgery, last 24
      h before sacrifice) alone or with N(G)-nitro-L-arginine methyl ester (L-NAME) (5
      mg/kg), L-arginine (200 mg/kg), and their combinations. Sulphasalazine (50 mg/kg)
      and 6-alpha-methylprednisolone (1 mg/kg) were given once daily intraperitoneally.
      BPC 157 accelerated parenterally or perorally the healing of colonic and skin
      defect, leading to the suitable closure of the fistula, macro/microscopically,
      biomechanically, and functionally (larger water volume sustained without fistula
      leaking). L-NAME aggravated the healing failure of colocutaneous fistulas, skin,
      and colon wounds (L-NAME groups). L-Arginine was effective only with blunted NO
      generation (L-NAME + L-arginine groups) but not without (L-arginine groups). All
      of the BPC 157 beneficial effects remained unchanged with blunted NO-generation
      (L-NAME + BPC 157 groups) and with NO substrate (L-arginine + BPC 157 groups) as
      well as L-NAME and L-arginine co-administration (L-NAME + L-arginine + BPC 157
      groups). Sulphasalazine was only moderately effective, and corticosteroid even
      had an aggravating effect.

PMID- 18818479
TI  - Caspase inhibition augmented oridonin-induced cell death in murine fibrosarcoma
      l929 by enhancing reactive oxygen species generation.
AB  - Oridonin, a diterpenoid isolated from Rabdosia rubescences, has been reported to
      have antitumor effects. In this study, the growth-inhibitory activity of oridonin
      for L929 cells was exerted in a time-and dose-dependent manner. After treatment
      with oridonin for 24 h, L929 cells underwent both apoptosis and necrosis as
      measured by an lactate dehydrogenase (LDH) activity-based assay. A rapid
      generation of reactive oxygen species (ROS) was triggered by oridonin, and
      subsequently up-regulation of phospho-p53 (ser 15) expression and an increased
      expression ratio of Bax/Bcl-2 was observed. Furthermore, there was a significant
      fall in mitochondrial membrane potential (MMP) and increase in caspase-3 activity
      after exposure to oridonin for 24 h. Surprisingly, the pan-caspase inhibitor z
      VAD-fmk and caspase3 inhibitor z-DEVD-fmk rendered L929 cells more sensitive to
      oridonin, rather than preventing oridonin-induced cell death. Oridonin and z-VAD
      fmk co-treatment not only resulted in an even higher ROS production, but also
      made a more significant reduction in the MMP. Pretreatment of ROS scavenger N
      acetylcysteine (NAC) led to a complete inhibition of oridonin-induced cell death,
      intracellular ROS generation, and MMP collapse. NAC treatment also reversed the
      potentiation of cell death by the pan-caspase inhibitor z-VAD-fmk. Taken
      together, these observations showed that oridonin-induced cell death in L929
      cells involved intracellular ROS generation, activation of phospho-p53 (ser 15),
      and up-regulation of the Bax/Bcl-2 ratio; and the augmented cell death by z-VAD
      fmk was dependent on an increased ROS production.

PMID- 18818480
TI  - Kv1.5 open channel block by the antiarrhythmic drug disopyramide: molecular
      determinants of block.
AB  - Kv1.5 is considered to be a potential molecular target for treatment of atrial
      fibrillation or flutter. Disopyramide is widely used in the treatment of atrial
      flutter and/or atrial fibrillation. The present study was undertaken to
      characterize the effects of disopyramide on currents mediated by Kv1.5 channels
      and to determine the putative binding site involved in the inhibitory effects of
      disopyramide. Experiments were carried out on wild-type and site directed mutated
      hKv1.5 channels expressed on HEK 293 cells using the patch-clamp technique.
      Disopyramide acting from the cytoplasmic side of the membrane produced blocking
      effects on Kv1.5 that exhibited several features typical of an open channel
      blocker. Ala-scanning mutagenesis of the Kv1.5 pore domain combined with
      macroscopic current analysis suggested that disopyramide interacted only with the
      Val512 residue that faces to the central cavity of the channel. Mutation of this
      key residue to Ala caused marked change in the IC(50) of disopyramide (22-fold).
      The single interaction between disopyramide and Val512 in the PVP region is able
      to change the mechanism of channel closure, reproducing the "foot-in-the-door"
      phenomenon.

PMID- 18818481
TI  - Modulation of adenylyl cyclase activity in rat striatal homogenate by
      dopaminergic receptors.
AB  - We have characterized the modulation of adenylyl cyclase (AC) activity by ligands
      of dopaminergic receptors in rat striatal homogenate and compared the results
      with receptor-ligand binding affinities. Despite the fact that rat striatum
      contains high level of both dopamine D(1) and D(2) receptors, only the D(1)
      specific AC activation by agonists could be determined. All D(1)-receptor
      agonists (dopamine, dihydrexidine, and A 77636) used were able to increase cAMP
      accumulation in a concentration-dependent manner, while D(1)-receptor antagonists
      (SCH23390, SKF83566, and butaclamol) blocked the effects induced by the
      aforementioned agonists. At the same time, the D(2)-receptor agonist quinpirole
      and antagonist sulpiride had no effect on cAMP accumulation in striatal
      homogenate neither on the basal level nor on the activated level of AC, while
      inhibited [(3)H]raclopride binding to these membranes. Comparing the ligands of
      the D(1) receptor in modulating the activity of AC and displacing D(1)-receptor
      specific radioligand [(3)H]SCH23390 binding revealed that the ligands modulate
      both of these processes with similar affinities. It indicates that under given
      experimental conditions, only dopamine D(1)-receptor-mediated stimulation of AC
      activity can be measured in membrane homogenate of rat striatum, while dopamine
      D(2)-receptor effects remain fully hidden.

PMID- 18818482
TI  - Sildenafil inhibits human pulmonary artery smooth muscle cell proliferation by
      decreasing capacitative Ca2+ entry.
AB  - Ca(2+) is a pivotal signal in human pulmonary artery smooth muscle cells (PASMCs)
      proliferation. Capacitative Ca(2+) entry (CCE) via the store-operated channel
      (SOC), which encoded by the transient receptor potential (TRP) gene, is an
      important mechanism for regulating intracellular Ca(2+) concentration
      ([Ca(2+)](i)) in PASMCs. Sildenafil, a potent type 5 nucleotide-dependent
      phosphodiesterase (PDE) inhibitor, has been proposed as a therapeutic tool to
      treat or prevent pulmonary arterial hypertension (PAH); however, the mechanism of
      its antiproliferative effect on PASMCs remains unclear. This study was designed
      to investigate the possible antiproliferative mechanism of sildenafil on human
      PASMCs, namely, its effect on the Ca(2+)-signal pathway. Cultured normal PASMCs
      were treated with endothelin-1 (ET-1) or ET-1 plus sildenafil separately. Cell
      number and viability were determined with a hemocytometer or MTT assay.
      [Ca(2+)](i) was measured by loading PASMCs with fura 2-AM. Expression of the
      TRPC1 gene and protein was detected by RT-PCR and Western blot, respectively. The
      results show that sildenafil dose-dependently inhibited the proliferation of
      PASMCs, the enhancement of basal [Ca(2+)](i) level, increase of CCE, and
      upregulation of TRPC expression induced by ET-1. These results suggest that
      sildenafil potently inhibits ET-1-induced PASMCs proliferation and downregulation
      of CCE and TRPC expression may be responsible for its antiproliferative effect.

PMID- 18818483
TI  - A role of ion channels in the endothelium-independent relaxation of rat
      mesenteric artery induced by resveratrol.
AB  - Recently it has been suggested that resveratrol relaxes different isolated
      arteries. The present study addressed the question whether different ion channels
      are involved in the endothelium-independent mechanism of vasodilatation induced
      by resveratrol. For that purpose, we tested the action of resveratrol on the rat
      mesenteric artery without endothelium. Resveratrol induced concentration
      dependent relaxation of rat mesenteric artery. Among the K(+)-channel blockers, 4
      amynopiridine (4-AP) moderately antagonized the resveratrol-induced relaxation,
      while glibenclamide, tetraethylammonium chloride, charybdotoxin, margatoxin, and
      barium chloride did not inhibit resveratrol-induced vasorelaxation. In rings,
      precontracted with 100 mM K(+), the relaxant responses to resveratrol were highly
      significantly shifted to the right compared to those obtained in rings
      precontracted with phenylephrine, but resveratrol-induced maximal relaxation was
      only slightly affected. In order to minimize the influence of K(+) channels and
      voltage-gated Ca(2+) channels (VGCCs) in vascular smooth muscle, the third
      contraction was made by 100 mM K(+) in the presence of nifedipine. The relaxant
      response to resveratrol was abolished. Thus, the mechanism of vasorelaxation
      induced by resveratrol probably involves activation of 4-AP-sensitive K(+)
      channels. Its ability to completely relax the mesenteric artery precontracted
      with K(+)-rich solution suggests that K(+) channel-independent mechanism(s) are
      involved in its vasorelaxant effect. It seems that interaction with VGCCs plays a
      part in this K(+) channel-independent effect of resveratrol.

PMID- 18818484
TI  - Changes in expression and localization of X-linked inhibitor of apoptosis protein
      (XIAP) in follicular granulosa cells during atresia in porcine ovaries.
AB  - Follicular selection predominantly depends on granulosa cell apoptosis in porcine
      ovaries, but the molecular mechanisms regulating the induction of apoptosis in
      granulosa cells during follicular selection remain incompletely understood. To
      determine the role of X-linked inhibitor of apoptosis protein (XIAP), which
      suppresses caspase-3, -7 and -9 activities and acts as an endogenous inhibitor of
      apoptotic cell death, in the regulation of granulosa cell apoptosis during
      follicular atresia, we examined the changes in the expression level and
      localization of XIAP mRNA and protein in granulosa cells during follicular
      atresia using reverse transcription-polymerase chain reaction (RT-PCR), in situ
      hybridization, Western blotting and immunohistochemistry, respectively. High
      levels of XIAP mRNA and protein were noted in the granulosa cells of healthy
      follicles, and decreased levels were noted during follicular atresia. In situ
      hybridization and immunohistochemistry demonstrated that XIAP mRNA and protein
      were strongly expressed in the granulosa cells of healthy follicles, but
      negative/trace stainings were noted in those of atretic follicles. The present
      findings strongly indicate that XIAP is a candidate molecule which acts as an
      anti-apoptotic/pro-survival factor by inhibiting intracellular apoptosis
      signaling and is involved in the regulation of apoptosis in porcine granulosa
      cells.

PMID- 18818485
TI  - Seasonal changes in spermatogenesis and immunolocalization of inhibin/activin
      subunits in the wild male ground squirrel (Citellus dauricus Brandt).
AB  - The objective of this study was to investigate the seasonal changes in
      spermatogenesis and the immunolocalization of the inhibin alpha and
      inhibin/activin (betaA and betaB) subunits during the breeding and non-breeding
      seasons in the wild male ground squirrel. The testicular weight and size and
      seminiferous tubule diameter were measured, and histological observations of
      testes were performed. The sections of the testes were immunostained by the
      avidin-biotin-peroxidase complex method (ABC) using polyclonal antisera raised
      against porcine inhibin alpha, inhibin/activin betaA and inhibin/activin betaB
      during the breeding and non-breeding seasons. There were marked variations in
      testicular weight and size and seminiferous tubule diameter between the breeding
      and non-breeding seasons, and all types of spermatogenic cells, including
      spermatozoa, were found in the breeding season. In addition, immunoreactivity was
      also detected for the inhibin alpha, betaA and betaB subunits in Sertoli and
      Leydig cells during the breeding season, but immunostaining was only present for
      the inhibin alpha and inhibin/activin betaB subunits in Sertoli cells during the
      non-breeding season. These results suggest that seasonal changes in testicular
      weight and size and seminiferous tubule diameter of wild ground squirrels are
      correlated with changes in spermatogenesis, and the cellular localization of the
      inhibin/activin subunits showed season related changes in the breeding and non
      breeding seasons.

PMID- 18818486
TI  - Thyroid hormone homeostasis in brain: possible involvement of adrenergic
      phenomenon in adult rat.
AB  - BACKGROUND: Imbalance in thyroid hormone concentrations has been linked with
      profound neurobehavioral alterations in the adult. Peripheral hypothyroidism is
      associated with a phenomenon of central thyroid hormone homeostasis in adult rat.
      This central homeostasis mechanism could be maintained by adrenergic interplay
      due to close physiological association between sympathetic nervous system
      activity and thyroid hormones. The central homeostasis is characterized by
      increased cerebrocortical synaptosomal T(3) content, deiodinase type II (DII)
      activity, and cAMP content. METHODS: We injected specific alpha- and beta
      adrenergic receptor (AR) agonists and antagonists along with an anti-thyroid drug
      to find out any AR-mediated action on central homeostasis. RESULTS: The alpha(2)
      AR agonist did not alter the onset of central homeostasis, but prolonged its
      duration. Similar prolongation was observed with alpha(2)-AR antagonist and beta
      AR agonist, but these compounds amplified the normal anti-thyroid drug-induced
      rise in cerebrocortical T(3) content on the day of onset of central homeostasis.
      Injections of the beta-AR antagonist did not cause any perturbations. All these
      observations have been supported by parallel changes in cerebrocortical DII
      activity, cAMP and [Ca(2+)](i) content. CONCLUSION: There emerges a close
      correlation between cerebral T(3) content, DII activity, cAMP and [Ca(2+)](i)
      content that are regulated by the AR system. Thus, thyroid hormone homeostasis in
      the adult mammalian brain is maintained primarily by the beta-adrenergic pathway
      along with an unexpected pharmacological involvement of the alpha-ARs.

PMID- 18818487
TI  - Inhibition of CD8+ T lymphocytes attenuates respiratory syncytial virus-enhanced
      allergic inflammation.
AB  - BACKGROUND: CD8+ T cells have an important role in the pathogenesis of
      respiratory virus-induced asthma exacerbations. However, the cellular mechanism
      of CD8+ T cells, linking viral respiratory infections to the development of
      airway inflammation, is not well defined. OBJECTIVES: To clarify the role of CD8+
      T cells in the development of respiratory virus-induced asthma exacerbations.
      METHODS: Using a murine model of prior ovalbumin exposure and subsequent
      respiratory syncytial virus infection, the airway responsiveness was assessed by
      barometric whole-body plethysmography. Airway eosinophils, lymphocytes,
      neutrophils as well as IFN-gamma, IL-4, IL-5 and IL-13 in bronchoalveolar lavage
      fluid were measured by Diff-Quick staining and ELISA. The frequency of cytokine
      producing CD8+ T lymphocytes in peribronchial lymph nodes was detected using 2
      color immunofluorescence analysis. Histological examinations were carried out
      using hematoxylin and eosin and immunohistochemistry. RESULTS: Anti-CD8
      monoclonal antibody (1 mg/kg) clearly inhibited increases in airway
      responsiveness to acetylcholine and markedly reduced the number of eosinophils,
      neutrophils, lymphocytes as well as IL-4, IL-5 and IL-13 levels in
      bronchoalveolar lavage fluid. Furthermore, the antibody also attenuated airway
      inflammation and CD8+ T lymphocyte infiltration in lung tissue. CONCLUSIONS:
      These findings suggest that CD8+ T lymphocytes play a critical role for the
      development of respiratory syncytial virus-induced airway inflammation and airway
      hyperresponsiveness.

PMID- 18818488
TI  - luxS-based quorum-sensing signaling affects Biofilm formation in Streptococcus
      mutans.
AB  - BACKGROUND: Quorum sensing (QS) is a process by which bacteria communicate with
      diffusible chemical signaling molecules called autoinducers (AIs). The
      autoinducer-2 signal (AI-2) produced by the LuxS protein mediates interspecies
      communication among Gram-positive and Gram-negative bacteria. In this study, we
      report that luxS-dependent QS is involved in the formation of Streptococcus
      mutans biofilms. METHODS: An S. mutans luxS mutant was constructed, and the
      differences in growth and biofilm formation were compared between the wild-type
      strain and the mutant strain. To quantificationally analyze the kinetic biofilm
      formation of the mutant strain, an assay of BioFilm Ring Test(R) was applied.
      RESULTS: There is a small increase in the growth of the luxS mutant strain after
      the stationary phase, compared with the parent strain. However during the
      exponential period, there were no significant differences. Using the BioFilm Ring
      Test(R), it was demonstrated that this luxS mutation was able to accelerate
      biofilm formation on a polystyrene surface during the mid-exponential growth
      phase. With 1% glucose treatment, even greater differences were observed between
      the mutant strain and its parental strain. CONCLUSION: These data suggest that a
      luxS-dependent signal may play an important role in the biofilm formation of S.
      mutans.

PMID- 18818489
TI  - Development of a genetic system for the denitrifying bacterium 'Aromatoleum
      aromaticum' strain EbN1.
AB  - Members of the betaproteobacterial 'Aromatoleum'/Azoarcus/Thauera cluster
      contribute to the biodegradation of aromatic and other recalcitrant compounds in
      anoxic soils and sediments. The metabolically versatile 'Aromatoleumaromaticum'
      strain EbN1 represents a model organism for this cluster, having already been
      studied on the physiological, proteogenomic and biochemical level. Here we report
      the development of a genetic system for 'A. aromaticum' strain EbN1 enabling
      unmarked deletion mutagenesis by heterologous recombination and subsequent
      complementation. The antibiotic sensitivity of strain EbN1 was characterized and
      optimal conditions for efficient cultivation on solid medium were established. A
      procedure for introducing foreign DNA into strain EbN1 by conjugation was
      developed. The effectiveness of the genetic system was demonstrated by unmarked
      in-frame deletion of ebdC2, encoding the gamma-subunit of a paralogous
      ethylbenzene dehydrogenase.

PMID- 18818490
TI  - Kidney transplantation improves sleep-related breathing in hemodialysis patients.
AB  - AIMS: To assess whether kidney transplantation improves sleep-related breathing
      disorders associated with hemodialysis. METHODS: A prospective study was carried
      out using full-night polysomnography. Nine hemodialysis patients (7 men and 2
      women, aged 42 +/- 16.2 years, BMI 26 +/- 3.7) who later received a successful
      kidney transplantation were evaluated. Main sleep quality and respiratory
      variables were recorded: number of dips in oxygen saturation (SaO(2)) > or =3%
      per hour of sleep; percentage of sleep time with SaO(2) <90%; percentage of sleep
      time in apnea and hypopnea, and sleep apnea/hypopnea index (AHI). RESULTS: After
      kidney transplantation, the AHI improved in 8 of the 9 patients (10 +/- 10.7 vs.
      4.9 +/- 6.1, p = 0.029). A decrease in the percentage of sleep time in
      apnea/hypopnea (5 +/- 6.8 vs. 0.7 +/- 1.1%, p = 0.008) and a reduction in the
      number of desaturations (25 +/- 26 vs. 12 +/- 11.2%, p = 0.010) were observed.
      CONCLUSIONS: Kidney transplantation improved respiratory events and nocturnal
      SaO(2) in hemodialysis patients.

PMID- 18818491
TI  - Normalization of brain tissue lactate after hyperbaric oxygen therapy in a
      progressive stroke patient.

PMID- 18818492
TI  - Moyamoya syndrome associated with optic nerve coloboma and mental retardation.

PMID- 18818493
TI  - Rapidly progressive cerebrovascular stenosis and recurrent strokes followed by
      improvement in HIV vasculopathy.

PMID- 18818494
TI  - Determinants of change in quality of life from 1 to 6 months following acute
      stroke--a comment.

PMID- 18818496
TI  - Acute inflammatory dilation of the cystic duct induced by a stone.

PMID- 18818497
TI  - Aberrant coronary vein as a hepatopetal collateral pathway for extrahepatic
      portal venous obstruction.

PMID- 18818498
TI  - Pancreatic fibrosis correlates with exocrine pancreatic insufficiency after
      pancreatoduodenectomy.
AB  - BACKGROUND: Obstruction of the pancreatic duct can lead to pancreatic fibrosis.
      We investigated the correlation between the extent of pancreatic fibrosis and the
      postoperative exocrine and endocrine pancreatic function. METHODS: Fifty-five
      patients who were treated for pancreatic and periampullary carcinoma and 19
      patients with chronic pancreatitis were evaluated. Exocrine pancreatic function
      was evaluated by fecal elastase-1 test, while endocrine pancreatic function was
      assessed by plasma glucose level. The extent of fibrosis, duct dilation and
      endocrine tissue loss was examined histopathologically. RESULTS: A strong
      correlation was found between pancreatic fibrosis and elastase-1 level less than
      100 microg/g (p < 0.0001), reflecting severe exocrine pancreatic insufficiency. A
      strong correlation was found between pancreatic fibrosis and endocrine tissue
      loss (p < 0.0001). Neither pancreatic fibrosis nor endocrine tissue loss were
      correlated with the development of postoperative diabetes mellitus. Duct dilation
      alone was neither correlated with exocrine nor with endocrine function loss.
      CONCLUSION: The majority of patients develop severe exocrine pancreatic
      insufficiency after pancreatoduodenectomy. The extent of exocrine pancreatic
      insufficiency is strongly correlated with preoperative fibrosis. The loss of
      endocrine tissue does not correlate with postoperative diabetes mellitus.
      Preoperative dilation of the pancreatic duct per se does not predict exocrine or
      endocrine pancreatic insufficiency postoperatively.

PMID- 18818499
TI  - Doubling time of carcinoembryonic antigen is a significant prognostic factor
      after the surgical resection of locally recurrent rectal cancer.
AB  - BACKGROUND: Patients undergoing a curative rectal cancer resection have a risk of
      developing locoregional recurrence. A curative resection for local recurrence is
      the option of improvement in prognosis. However, a curative resection is
      sometimes too invasive and should be considered in selected patients. METHODS: A
      total of 43 patients with locally recurrent rectal cancer who had been treated by
      operation between 1989 and 2007 were retrospectively reviewed and the factors,
      including doubling time of carcinoembryonic antigen (CEA-dt), were analyzed.
      RESULTS: The 5-year overall survival rate after the operation for local
      recurrence was 50.8%. Gender, presence of distant metastasis, tumor size, CEA-dt
      and curability were found to be significant prognostic factors. A multivariate
      analysis demonstrated the presence of distant metastasis, CEA-dt and tumor size
      to be significant prognostic factors for overall survival. The 5-year overall
      survival rates of patients with a CEA-dt > or =150 days and a tumor size <5 cm
      were 76.9%. CONCLUSIONS: The tumor size and CEA-dt were useful prognostic factors
      that were recognizable before surgery. Patients with locally recurrent rectal
      cancer with a CEA-dt > or =150 days and a recurrent tumor size <5 cm are
      considered to be good candidates for surgery.

PMID- 18818500
TI  - Mechanical bowel preparation: are we ready for a paradigm shift?

PMID- 18818501
TI  - Prenatal detection of a subtle unbalanced chromosome rearrangement by
      karyotyping, FISH and array comparative genomic hybridization.
AB  - OBJECTIVES: To explore the advantages and limitations of comparative genomic
      hybridization to BAC arrays (array CGH) for prenatal diagnosis of a fetus with
      anomalies and a chromosome abnormality. METHODS: We used karyotype analysis, FISH
      and array CGH to investigate an unbalanced chromosome rearrangement. RESULTS: We
      report a case of a fetus with ultrasound anomalies at 11 weeks' gestation and an
      unbalanced chromosome translocation [46,XX,der(13)t(2;13)(p25.1;q32)pat].
      Initially, a chromosome 13 deletion was reported from G-banded chromosome
      analysis and 13q subtelomere FISH. The involvement of chromosome 2 was determined
      after a balanced translocation was identified in the father,
      46,XY,t(2;13)(p25.1;q32). Array CGH confirmed the fetal abnormality as partial
      trisomy of the short arm chromosome 2 and partial monosomy of the long arm of
      chromosome 13. The abnormalities identified by ultrasound studies and autopsy
      appear to be most consistent with 13q deletion syndrome. CONCLUSIONS: Array CGH
      successfully identified a subtle unbalanced chromosome complement in a fetus with
      multiple ultrasound anomalies. If array CGH had been performed along with the
      fetal karyotype, the cryptic partial trisomy 2 could have been identified in a
      more timely manner to assist in the prenatal counseling of this family.

PMID- 18818502
TI  - How imprecise may the measurement of fetal nuchal translucency be without
      worsening first-trimester screening?
AB  - OBJECTIVE: First-trimester screening (FTS) has a trisomy 21 detection rate of
      about 90%. Despite profound training, the practically reached measurement quality
      of nuchal translucency (NT) is probably not optimal. This study investigated the
      impact of measurement errors on FTS. METHODS: The data on 10,116 combined FTSs
      were obtained in a multicenter study. Risk assessment was performed by the JOY
      software following the Nicolaides risk calculation principles. To investigate the
      impact of measurement errors, the NT values were artificially altered and the
      adjusted risks were recalculated. Test performance parameters were obtained and
      compared with the correct measurements. RESULTS: In this study 85 fetuses were
      genetically affected. The screening was wrongly inconspicuous in 12 cases and in
      479 cases the FTS offered false-positive results. An assumed NT error of +/-0.1
      mm already causes a highly significant change in the false-positive rate. A
      difference of -0.2 mm leads to a visible change in false negatives. DISCUSSION:
      This study demonstrates that even the smallest deviations will significantly
      affect the false-negative rate. The detection of really diseased fetuses is
      influenced at a -0.2-mm measurement error. Therefore the NT measurement has to be
      as precise as possible.

PMID- 18818503
TI  - Uterine prolapse in pregnancy: a rare condition an obstetrician should be
      familiar with.
AB  - Uterine prolapse complicating pregnancy is a rare event. Early recognition is
      essential in order to avoid possible maternal and fetal risks. We report the case
      of a 37-year-old pregnant woman who presented to the antenatal outpatient clinic
      with uterine prolapse at 31(+1) weeks of gestation. Sonographic examination
      revealed an enlarged fibromatous uterus. She was conservatively treated on an
      inpatient basis. Two weeks later she underwent an emergency cesarean section
      because of preterm uterine contractions. A live male neonate weighing 1,900 g was
      delivered. We believe that conservative management with bed rest, followed by an
      elective cesarean section, may ensure an uncomplicated gestation and an
      uneventful delivery.

PMID- 18818504
TI  - X pentasomy in an intracytoplasmic sperm injection pregnancy detected by nuchal
      translucency testing.
AB  - Althoughmaternally derived X pentasomy following intracytoplasmic sperm injection
      (ICSI) is rare, prenatal detection of a case offers insight into etiology and
      diagnosis. A 29-year-old gravida 1 whose pregnancy resulted from ICSI was
      referred for ultrasound screening at 11 weeks' gestation. Nuchal translucency
      thickness was 3.2 mm, and the fetal nasal bone was absent. Subsequent evaluation
      revealed karyotype 49,XXXXX. DNA microsatellite analysis showed the extra X
      chromosomes were maternal in origin. Termination of pregnancy was performed at 15
      weeks. Because of the increased risk of sex chromosomal abnormalities in ICSI
      pregnancies, patients should be counseled prior to fertilization and standard
      prenatal care should include nuchal translucency measurement and any other
      elements necessary for indicated pregnancies to obtain a diagnosis.

PMID- 18818505
TI  - Pain management.
AB  - Both pancreatitis and pancreatic cancer patients suffer from severe pain. For the
      pancreatitis patient, pain is often the stimulus for going to the doctor to
      receive diagnosis. This pain originates from increased pressure in the pancreatic
      duct due to the inflammation and scarring associated with pancreatitis and/or
      inflammation of pancreatic nerves, since this organ is richly supplied with
      nerves and chronic inflammation in the area may also lead to the release of
      various substances that stimulate these nerves. In patients with unresectable
      pancreatic cancer, severe abdominal and back pain is a significant complication
      due to the spread of the disease to nerves in the surrounding area or pressure on
      nearby organs.

PMID- 18818506
TI  - Primers on molecular pathways--pain and opioid receptors, I.
AB  - The conquest of pain would be in our mind, perhaps, the most important discovery
      in medicine to impact on patient suffering. In our specialty, several pancreatic
      diseases are characterized by severe discomfort. For instance, pancreatic cancer
      is one of the most painful diseases from which a human being can suffer. Chronic
      pancreatitis is similarly debilitating. Therefore, the field of pain research and
      management is of paramount importance to pancreatologists. Certainly, this area
      is very extensive and growing. However, as applied to pancreatic diseases, we are
      still in our infancy. The major problem is that, beyond the anecdotal
      publication, we do not know how pancreatic pain is originated and maintained.
      Therefore, significant efforts must be made to improve our understanding of the
      mechanisms of both acute and chronic pain, as well as of how we can provide our
      patients with a more dignified life and sometimes a more peaceful end stage of
      life. Thus, it is in this spirit that we are developing several articles on
      'molecular pathways' focused on describing the molecular machinery underlying
      pancreatic pain, with the objective of both creating a better understanding of
      this problem as well as of generating enthusiasm for outstanding investigators to
      come to this emerging and critical field of pancreatology. Here, the first
      article will focus on the mechanism underlying the effect of morphine and
      opioids. It is our dearest goal that the basic scientist gets very excited about
      dissecting this problem, and that the clinician not only has simple, one-stop
      reading material, but that this reading will help him/her understand work
      published on pancreatic pain and hopefully also initiate clinical trials
      targeting this pathway.

PMID- 18818507
TI  - Differential diagnosis of pancreatic tumors by molecular analysis of clinical
      specimens.
AB  - OBJECTIVE: To describe the capabilities and limitations of the current state of
      the art in pancreatic cancer diagnostics and to discuss recent progress in the
      development of novel, highly accurate molecular diagnostic approaches. RESULTS:
      Molecular analyses currently under evaluation as novel diagnostic tests include
      detection of point mutations, genomic imbalances, aberrant methylation patterns
      and gene expression changes on the mRNA and protein levels in pancreatic juice,
      fine needle aspiration biopsies and brush cytologies. CONCLUSIONS: In exploratory
      studies, several candidate molecular markers show great potential to serve as
      general indicators of malignancy, but need to be validated in large, controlled,
      prospective studies. Multiplexing of diagnostic tests, e.g. in the form of
      specialized DNA microarrays, may provide more differentiated diagnoses such as
      the distinction of various tumor types or prognostic information for individual
      patients. The MolDiag-Paca consortium is strongly engaged in advancing these
      developments on a European level.

PMID- 18818508
TI  - International registries of families at high risk of pancreatic cancer.
AB  - PURPOSE: To describe the need for multinational registries of families at high
      risk of pancreatic cancer and the issues surrounding identification of such
      families. RESULTS: A consensus position was published describing surveillance of
      individuals at high risk of pancreatic cancer. Hereditary pancreatitis patients,
      people with Peutz-Jeghers syndrome, individuals with CDKN2A or BRCA1/2 mutations
      with a family history of pancreatic cancer and kindred with multiple pancreatic
      cancers were considered suitable for research-based screening. Mutations
      responsible for familial predisposition are mostly unknown, although BRCA2
      mutations have been identified in some families and a mutation in the palladin
      gene has been shown to segregate with pancreatic cancer in one kindred. Specific
      autosomal dominant inheritance of pancreatic cancer risk seems to involve
      anticipation; this finding aids identification of families and determination of
      individual risk. Diabetes mellitus is an early symptom of pancreatic cancer, but
      recent publications suggest that it may not be a significant predisposing factor;
      this remains controversial. However, in the context of hereditary pancreatitis,
      diabetes probably does predispose to pancreatic cancer as shown in a recent
      description of French families. CONCLUSION: Appropriate inclusion of patients
      within registries of high-risk families provides a framework for secondary
      screening and research on risk stratification and early tumorigenesis. and IAP.

PMID- 18818509
TI  - 5-Nitro-2-(3-phenylpropylamino)benzoic acid is a GPR35 agonist.
AB  - GPR35 is a Gi/o- and G16-coupled receptor abundantly expressed in
      gastrointestinal tissues and immune cells. Kynurenic acid (a tryptophan
      metabolite and ionotropic glutamate receptor antagonist) and zaprinast (a
      phosphodiesterase inhibitor) are GPR35 agonists. Here, we show that the chloride
      channel blocker 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB) is also a
      GPR35 agonist. NPPB activates the GPR35-Gi/o and GPR35-G16 pathways in human
      embryonic kidney 293 (HEK293) cells and induces intracellular calcium
      mobilization in a concentration-dependent manner in HEK293 cells coexpressing
      human, rat or mouse GPR35 and the chimeric G protein G(qi5). These results
      suggest a novel pharmacological activity of NPPB and will provide useful
      information to search for more potent and selective GPR35 agonists.

PMID- 18818510
TI  - Anti-inflammatory effects of the methanol extract of Sedum telephium ssp. maximum
      in lipopolysaccharide- stimulated rat peritoneal macrophages.
AB  - Sedum telephium ssp. maximum is a medicinal plant that possesses anti
      inflammatory, analgesic and keratolytic properties. We investigated the anti
      inflammatory activity of its methanolic extract (STME) in rat peritoneal
      macrophages (MPhis) stimulated with lipopolysaccharide from Salmonella
      enteritidis. After stimulation with 10 microg/ml of LPS, MPhis were coincubated
      with different doses of STME (8, 16 and 32 microg/ml) or RPMI medium alone using
      different times of incubation. STME reduced levels of tumor necrosis factor
      alpha, both mRNA and its protein, and significantly decreased IL-1beta and IL-6
      production. Moreover, STME inhibited inducible nitric oxide synthase expression
      and blunted nitrite release and inhibited both extracellular signal-regulated
      kinase 1/2 and c-Jun N-terminal kinase activation in lipopolysaccharide
      stimulated MPhis. Data show that STME might be useful as a potential anti
      inflammatory agent.

PMID- 18818511
TI  - Targeting cancer cells by synthetic lethality: autophagy and VHL in cancer
      therapeutics.
AB  - Standard cytotoxic agents for treating cancer were developed based on their
      effectiveness to kill rapidly dividing cells, not on their ability to selectively
      kill cancer cells and spare normal tissue. Much of contemporary cancer research
      is aimed at identifying specific molecular features of cancers to directly target
      tumor cells with the hope of reducing or eliminating unwanted side effects.
      Targeted therapy for the treatment of cancer can be divided into two main
      categories: monoclonal antibodies and small molecules. In this Perspective, we
      review the approach of synthetic lethality to target cancer, specifically renal
      cell carcinoma. The concept of synthetic lethality is used to describe a genetic
      interaction of two non-allelic and non-lethal genes that when mutated
      simultaneously results in cell death. Recently, we identified a compound, STF
      62247, that functions in a synthetic lethal manner to the loss of VHL, a mutation
      found in the majority of renal cell carcinomas.

PMID- 18818512
TI  - Consorting kinases, end of destruction and birth of a spindle.
AB  - Centrosomes (spindle pole body in yeast) constitute the two poles of the bipolar
      mitotic spindle and play a prominent role in the segregation of chromosomes
      during mitosis. Like chromosomes, the centrosome inherited from the progenitor
      cell duplicates once in each division cycle, following which the sister
      centrosomes segregate away from each other to assemble a short spindle upon
      initiation of mitosis. Cdh1, an activator of the E3 ubiquitin ligase APC
      (Anaphase Promoting Complex), is a potent inhibitor of centrosome segregation and
      suppresses spindle assembly during S phase by mediating proteolytic destruction
      of the microtubule associated proteins (MAPs) required for centrosome separation.
      A recent study in yeast suggests that concerted action by two prominent kinases
      Cdk1 and polo are required to bring this destruction to a halt by inactivating
      Cdh1 and to facilitate spindle assembly. This is an effective strategy for the
      modulation of the activities of cell cycle regulators that require multiple
      phosphorylation. The control circuit involving Cdh1, Cdk1, Polo and MAPs may be
      also targeted by other cellular networks in contexts that demand the restraining
      of spindle dynamics.

PMID- 18818513
TI  - Identification of a synaptosome-associated form of BAG3 protein.

PMID- 18818514
TI  - Expression of Arl2 is associated with p53 localization and chemosensitivity in a
      breast cancer cell line.
AB  - In mammalian cells, ADP ribosylation factor like 2 (Arl2) has been shown to form
      a complex with tubulin binding cofactor D (TBC-D) and the tumor suppressor
      protein phosphatase 2A (PP2A). We have previously shown that alterations in Arl2
      protein content were associated with corresponding modifications of the tumor
      suppressor PP2Ac protein content in breast cancer cells. Here, we show that
      modified Arl2 expression level influences sensitivity to various anticancer
      compounds such as taxol, navelbine, gemcitabine and doxorubicin in MCF7 derived
      cell lines. Modifications of Arl2 expression levels were also associated with an
      altered phosphorylation status and/or cellular sublocalization of certain PP2A
      targets such as p53, a key mediator of chemotherapy-induced apoptosis. A
      decreased level of Arl2 expression was associated with an increase of phospho
      ser15-p53, a form which was found to be preferentially bound to microtubules.
      Assays using okadaic and cantharidic acid, two different PP2A inhibitors, showed
      an increase in microtubule-bound phospho-p53 and reduced sensitivity to
      chemotherapy. Our results suggest that Arl2 could, via PP2A, influence p53
      phosphorylation status. Certain forms of phosphorylated p53 demonstrating
      increased binding to microtubules appear to be less prone to nuclear
      translocation after exposure to chemotherapeutic agents, thereby possibly
      contributing to reduced chemosensitivity.

PMID- 18818515
TI  - SCF(Fbx4/alphaB-crystallin) E3 ligase: when one is not enough.
AB  - Cell cycle progression is determined by the balance of positive regulators,
      cyclin-dependent-protein kinases (cdks) relative to negative regulators, cyclin
      dependent kinase inhibitors (ckis). D-type cyclins, (D1, D2, D3) are expressed in
      a tissue-specific manner and are the first cyclins to be expressed during the
      cell cycle. Of the three D-type cyclins, cyclin D1 is most frequently
      overexpressed in human cancer. The mechanisms of cyclin D1 overexpression can be
      attributed to gene amplification, transcriptional activation and altered protein
      degradation; of these, inhibition of ubiquitin-dependent proteolysis of cyclin D1
      is thought to be a primary mechanism of cyclin D1 overexpression in human tumors.
      Because the identity of the regulators of cyclin D1 proteolysis were largely
      undefined until recently, it had not been possible to determine whether this
      regulatory network was directly targeted in primary cancer. Cyclin D1 proteolysis
      requires phosphorylation by GSK3beta at Thr-286; additional work recently
      established that p286-D1 is a substrate for the SCF(Fbx4/alphaB-crystallin) E3
      ligase. This discovery has facilitated an analysis of SCF(Fbx4/alphaB-crystallin)
      ligase in human cancers. This recent work revealed that Fbx4 is subject to
      mutational inactivation in human cancer, resulting in the accumulation of cyclin
      D1. Molecular analysis of this ligase has revealed striking regulatory features
      that contribute to regulated cyclin D1 accumulation and support the idea that
      Fbx4 is a bona fide tumor suppressor.

PMID- 18818516
TI  - X-ray structure of the complex of regulatory subunits of human DNA polymerase
      delta.
AB  - The eukaryotic DNA polymerase delta (Pol delta) participates in genome
      replication, homologous recombination, DNA repair and damage tolerance.
      Regulation of the plethora of Pol delta functions depends on the interaction
      between the second (p50) and third (p66) non-catalytic subunits. We report the
      crystal structure of p50*p66(N) complex featuring oligonucleotide binding and
      phosphodiesterase domains in p50 and winged helix-turn-helix N-terminal domain in
      p66. Disruption of the interaction between the yeast orthologs of p50 and p66 by
      strategic amino acid changes leads to cold-sensitivity, sensitivity to
      hydroxyurea and to reduced UV mutagenesis, mimicking the phenotypes of strains
      where the third subunit of Pol delta is absent. The second subunits of all B
      family replicative DNA polymerases in archaea and eukaryotes, except Pol delta,
      share a three-domain structure similar to p50*p66(N), raising the possibility
      that a portion of the gene encoding p66 was derived from the second subunit gene
      relatively late in evolution.

PMID- 18818517
TI  - The insulin-like growth factor system as a potential therapeutic target in
      gastrointestinal stromal tumors.
AB  - The majority of gastrointestinal stromal tumors (GISTs) are characterized by
      oncogenic gain-of-function mutations in the receptor tyrosine kinase (RTK) c-KIT
      with a minority in PDGFRalpha. Therapy for GISTs has been revolutionized by the
      use of the selective tyrosine kinase inhibitor imatinib mesylate (IM). For the
      subset (approximately 10-15%) of GISTs that lack oncogenic mutations in these
      receptors, the genetic changes driving tumorigenesis are unknown. We recently
      reported that the gene encoding the insulin-like growth factor 1 receptor (IGF
      1R) is amplified in a subset of GISTs, and the IGF-1R protein is overexpressed in
      wild-type and pediatric GISTs. In this report we present a more complete picture
      of the involvement of components of the insulin-like growth factor-signaling
      pathway in the pathogenesis of GISTs. We also discuss how the IGF pathway may
      provide additional molecular targets for the treatment of GISTs that respond
      poorly to IM therapy.

PMID- 18818518
TI  - HIV-1 gp41 fusogenic function triggers autophagy in uninfected cells.
AB  - Cell-expressed HIV-1 envelope glycoproteins (gp120 and gp41, called Env) induce
      autophagy in uninfected CD4 T cells, leading to their apoptosis, a mechanism most
      likely contributing to immunodeficiency. The presence of CD4 and CXCR4 on target
      cells is required for this process, but Env-induced autophagy is independent of
      CD4 signaling. Here we demonstrate that CXCR4-mediated signaling pathways are not
      directly involved in autophagy and cell death triggering. Indeed, cells stably
      expressing mutated forms of CXCR4, unable to transduce different Gi-dependent and
      -independent signals, still undergo autophagy and cell death after coculture with
      effector cells expressing Env. After gp120 binding to CD4 and CXCR4, the N
      terminus fusion peptide (FP) of gp41 is inserted into the target membrane, and
      gp41 adopts a trimeric extended pre-hairpin intermediate conformation, target of
      HIV fusion inhibitors such as T20 and C34, before formation of a stable six-helix
      bundle structure and cell-to-cell fusion. Interestingly, Env-mediated autophagy
      is triggered in both single cells (hemifusion) and syncytia (complete fusion),
      and prevented by T20 and C34. The gp41 fusion activity is responsible for Env
      mediated autophagy since the Val2Glu mutation in the gp41 FP totally blocks this
      process. On the contrary, deletion of the C-terminal part of gp41 enhances Env
      induced autophagy. These results underline the major role of gp41 in inducing
      autophagy in the uninfected cells and indicate that the entire process leading to
      HIV entry into target cells through binding of Env to its receptors, CD4 and
      CXCR4, is responsible for autophagy and death in the uninfected, bystander cells.

PMID- 18818519
TI  - The let-7 microRNA interfaces extensively with the translation machinery to
      regulate cell differentiation.
AB  - MicroRNAs (miRNAs) are noncoding RNAs that regulate numerous target genes through
      a posttranscriptional mechanism and thus control major developmental pathways.
      The phylogenetically conserved let-7 miRNA regulates cell proliferation and
      differentiation, thus functioning as a key regulator of developmental timing in
      C. elegans and a tumor suppressor gene in humans. Using a reverse genetic screen,
      we have identified genetic interaction partners of C. elegans let-7, including
      known and novel potential target genes. Initial identification of several
      translation initiation factors as suppressors of a let-7 mutation led us to
      systematically examine genetic interaction between let-7 and the translational
      machinery, which we found to be widespread. In the presence of wild-type let-7,
      depletion of the translation initiation factor eIF3 resulted in precocious cell
      differentiation, suggesting that developmental timing is translationally
      regulated, possibly by let-7. As overexpression of eIF3 in humans promotes
      translation of mRNAs that are also targets of let-7-mediated repression, we
      suggest that eIF3 may directly or indirectly oppose let-7 activity. This might
      provide an explanation for the opposite functions of let-7 and eIF3 in regulating
      tumorigenesis.

PMID- 18818520
TI  - Crystallographic and mutational studies of seryl-tRNA synthetase from the
      archaeon Pyrococcus horikoshii.
AB  - Seryl-tRNA synthetase (SerRS) catalyzes the ligation of serine to the 3'-end of
      serine tRNA (tRNA(Ser)), which is typical of the type-2 tRNAs characterized by a
      long extra arm. The SerRSs are divided into two types, the archaeal/eukaryal and
      bacterial types. In this study, we solved the crystal structures of the SerRS
      from the archaeon Pyrococcus horikoshii bound with 5'-O-[N-(L-seryl)-sulfamoyl]
      adenosine at 2.6 A and with ATP at 2.8 A, as well as in the apo form at 3.0 A. P.
      horikoshii SerRS recognizes the seryl and adenylate moieties in a manner similar
      to those of the bacterial and mitochondrial SerRSs from Thermus thermophilus and
      Bos taurus, respectively, but different from that of the unusual SerRS from the
      methanogenic archaeon Methanosarcina barkeri. P. horikoshii SerRS efficiently
      aminoacylated not only P. horikoshii tRNA(Ser) but also bacterial tRNA(Ser)s from
      T. thermophilus and Escherichia coli. Models of P. horikoshii SerRS bound with
      the T. thermophilus and P. horikoshii tRNA(Ser)s suggested that the helical
      domain of P. horikoshii SerRS is involved in the extra arm binding. This region
      of P. horikoshii SerRS has additional basic residues as compared with T.
      thermophilus SerRS, and a Trp residue specific to the archaeal/eukaryal SerRSs.
      Mutational analyses revealed that the basic and Trp residues are important for
      tRNA aminoacylation. P. horikoshii SerRS has the archaea-specific insertion,
      which collaborates with the core domain to form a basic channel leading to the
      active site. Two sulfate ions are bound to the channel, suggesting that the tRNA
      3' region might bind to the channel.

PMID- 18818521
TI  - MdmX regulates transformation and chromosomal stability in p53-deficient cells.
AB  - The cellular homologues Mdm2 and MdmX play critical roles in regulating the
      activity of the p53 tumor suppressor in damaged and non-damaged cells and during
      development in mice. Recently, we have utilized genetically defined primary cells
      and mice to reveal that endogenous levels of MdmX can also suppress multipolar
      mitosis and transformation in hyperploid p53-deficient cells and tumorigenesis in
      p53-deficient mice. These MdmX functions are not shared by Mdm2, and are distinct
      from the well-established ability of MdmX to complex with and inhibit p53
      activity. Here we discuss some of the ramifications of MdmX loss in p53-deficient
      cells and mice, and we explore further the fate of MdmX/p53-double null embryonic
      fibroblasts undergoing multi-polar cell division using time-lapse video
      microscopy. We also discuss the relationship between chromosomal loss, cell
      proliferation, and the tumorigenic potential of p53-deficient cells lacking MdmX.

PMID- 18818522
TI  - Mutant p53 protein localized in the cytoplasm inhibits autophagy.
AB  - The knockout, knockdown or chemical inhibition of p53 stimulates autophagy.
      Moreover, autophagy-inducing stimuli such as nutrient depletion, rapamycin or
      lithium cause the depletion of cytoplasmic p53, which in turn is required for the
      induction of autophagy. Here, we show that retransfection of p53(-/-) HCT 116
      colon carcinoma cells with wild type p53 decreases autophagy down to baseline
      levels. Surprisingly, one third among a panel of 22 cancer-associated p53 single
      amino acid mutants also inhibited autophagy when transfected into p53(-/-) cells.
      Those variants of p53 that preferentially localize to the cytoplasm effectively
      repressed autophagy, whereas p53 mutants that display a prominently nuclear
      distribution failed to inhibit autophagy. The investigation of a series of
      deletion mutants revealed that removal of the DNA-binding domain from p53 fails
      to interfere with its role in the regulation of autophagy. Altogether, these
      results identify the cytoplasmic localization of p53 as the most important
      feature for p53-mediated autophagy inhibition. Moreover, the structural
      requirements for the two biological activities of extranuclear p53, namely
      induction of apoptosis and inhibition of autophagy, are manifestly different.

PMID- 18818523
TI  - p53 in autophagy control.

PMID- 18818524
TI  - SIRT1 protein levels in cancer: tuning SIRT1 to the needs of a cancer cell.

PMID- 18818525
TI  - Dihydrocapsaicin (DHC), a saturated structural analog of capsaicin, induces
      autophagy in human cancer cells in a catalase-regulated manner.
AB  - Although capsaicin, a pungent component of red pepper, is known to induce
      apoptosis in several types of cancer cells, the mechanisms underlying capsaicin
      induced cytotoxicity are unclear. Here, we showed that dihydrocapsaicin (DHC), an
      analog of capsaicin, is a potential inducer of autophagy. DHC was more cytotoxic
      than capsaicin in HCT116, MCF-7 and WI38 cell lines. Capsaicin and DHC did not
      affect the sub-G(1) apoptotic peak, but induced G(0)/G(1) arrest in HCT116 and
      MCF-7 cells. DHC caused the artificial autophagosome marker GFP-LC3 to
      redistribute and upregulated expression of autophagy-related proteins. Blocking
      of autophagy by 3-methyladenine (3MA) as well as siRNA Atg5 induced a high level
      of caspase-3 activation. Although pretreatment with zVAD completely inhibited
      caspase-3 activation by 3MA, it did not prevent cell death. DHC-induced autophagy
      was enhanced by zVAD pretreatment, as shown by increased accumulation of LC3-II
      protein. DHC attenuated basal ROS levels through catalase induction; this effect
      was enhanced by antioxidants, which increased both LC3-II expression and caspase
      3 activation. The catalase inhibitor 3-amino-1,2,4-triazole (3AT) abrogated DHC
      induced expression of LC3-II, overexpression of the catalase gene increased
      expression of LC3-II protein, and knockdown decreased it. Additionally, DHC
      induced autophagy was independent of p53 status. Collectively, DHC activates
      autophagy in a p53-independent manner and that may contribute to cytotoxicity of
      DHC.

PMID- 18818526
TI  - Metastasis and AKT activation.
AB  - Metastasis is responsible for 90% of cancer patient deaths. More information is
      needed about the molecular basis for its potential detection and treatment. The
      activated AKT kinase is necessary for many events of the metastatic pathway
      including escape of cells from the tumor's environment, into and then out of the
      circulation, activation of proliferation, blockage of apoptosis, and activation
      of angiogenesis. A series of steps leading to metastatic properties can be
      initiated upon activation of AKT by phosphorylation on Ser-473. These findings
      lead to the question of how this activation is connected to metastasis. Activated
      AKT phosphorylates GSK-3beta causing its proteolytic removal. This increases
      stability of the negative transcription factor SNAIL, thereby decreasing
      transcription of the transmembrane protein E-cadherin that forms adhesions
      between adjacent cells, thereby permitting their detachment. How is AKT
      hyperactivated in metastatic cells? Increased PI3K or TORC2 kinase activity- or
      decreased PHLPP phosphatase could be responsible. Furthermore, a positive
      feedback mechanism is that the decrease of E-cadherin lowers PTEN and thereby
      increases PIP3, further activating AKT and metastasis.

PMID- 18818527
TI  - Health human resources and public-private partnerships: understanding their
      contributions to Canada's transforming healthcare environment.
AB  - This article sets out some of the main elements that characterize Canada's
      transforming healthcare environment and that largely form the raison d'etre for
      new approaches to health human resources and for the emergence of public-private
      partnerships. It then presents core findings from a meeting of healthcare CEOs
      held in Banff as well as the author's views based on his experiences as president
      and CEO of Kingston General Hospital.

PMID- 18818528
TI  - Leading complex change in healthcare: 10 lessons learned.
AB  - This article reports on the transfer of perinatal services at St. Joseph's Health
      Care, in London, Ontario, to London Health Sciences Centre (LHSC). The transfer
      of perinatal programs, services and people/providers to LHSC generates concern in
      key stakeholders with respect to a potential negative impact on the quality of
      care delivery, staff work life and morale, team performance, recruitment,
      retention and other performance indicators. Our main task was to establish
      "readiness and capacity for the change" in the years leading up to the actual
      transfer, with a strong focus on attending to the human side of the change,
      clinical and cultural alignment. We describe the external and internal challenges
      of the transfer and the approach that we took in building readiness, and end with
      10 lessons learned and applied throughout the change process.

PMID- 18818529
TI  - The beneficial role of a judicial process when "everything" is too much?
AB  - This narrative is written with the intent to encourage physicians as well as
      other healthcare professionals to use judicial processes, such as those provided
      by the Ontario Consent and Capacity Board, to help resolve conflict with
      treatment decisions between care providers and decision-makers. Through the
      presentation of a fictional yet common case scenario, it is argued that after all
      attempts at mediation have been attempted that the timely use of a third party is
      in the patient's, the family's and the healthcare team's best interests.

PMID- 18818530
TI  - The British Columbia Alliance on Telehealth Research and Policy.
AB  - The past decade has seen a growing trend in the establishment of partnerships
      between university-based researchers and non-university stakeholders. one such
      initiative led to the creation of the British Columbia Alliance on Telehealth
      Policy and Research (BCATPR), now in its third year of operation. This article
      outlines the development and operation of BCATPR, with specific emphasis on the
      engagement process adopted, as well as the strengths and challenges associated
      with this model of partnership between university-based researchers adn health
      authority policy makers.

PMID- 18818531
TI  - On the journey to a culture of patient safety.
AB  - In 2005, our hospital participated in a Canadian Council on Health Services
      Accreditation (CCHSA) Patient Safety Cultural Assessment project. Online survey
      results collected and analyzed by CCHSA demonstrated numerous opportunities for
      our organization to improve its patient safety culture. An eight-point Patient
      Safety Plan was created, and over the following two years, numerous patient
      safety initiatives were implemented. In 2007, the Patient Safety Cultural
      Assessment was repeated using the same survey instrument and an online survey
      response method. Results showed only very minor positive improvements in our
      culture.

PMID- 18818532
TI  - Yes, Virginia, there are system benefits to be gained from providing patients
      access to their own health information.
AB  - The world has evolved into "The Informed Society" where consumers from all types
      of businesses and industries play larger roles in both the purchase and the
      development of products and services. But in health care, such " grass roots"
      contributions have been slower to come to the fore. The first step in the
      evolution is access to their own health information--providing patients access to
      their own health information within electronic health records. As this
      information becomes available, additional education programs will have to be
      developed to safely activate and empower patients as partners in their care.

PMID- 18818533
TI  - Employers, home support workers and elderly clients: identifying key issues in
      delivery and receipt of home support.
AB  - The Nexus Home Care Project examines the experiences of employers, home support
      workers and elderly clients and their family members in the delivery and receipt
      of home support services. The primary purpose of this research is to identify
      salient issues in the delivery and receipt of home support services to elderly
      individuals from the perspective of employers, home support workers and clients.
      The data for this study, funded by the Canadian Institutes of Health Research,
      are derived from in-depth interviews with home support employers (n=11), home
      support workers (n=32) and elderly clients (n=14) in British Columbia. Employers
      emphasized recruitment and retention and the increasing complexity of client
      needs, and raised questions regarding the appropriateness of home support as a
      part of the healthcare continuum. Home support workers stressed scheduling and
      time demands, the tension in providing intimate ongoing care at an emotional
      distance and the balance between tasks outlined in the care plan and the needs
      and wants of elderly clients. Elderly clients indicated an ongoing need to
      prepare for and manage services and expressed a need for companionship. Findings
      are discussed as they inform and extend our understanding of the key tensions in
      home support. Strategies for addressing these tensions are also identified.

PMID- 18818534
TI  - Home care's unique challenges.

PMID- 18818535
TI  - One eye down and the other looking ahead: moving on in home support and community
      care.

PMID- 18818536
TI  - Tapestry of care: who provides care in the home?

PMID- 18818537
TI  - Recommended permissible noise criteria for occupied, newly constructed or
      renovated hospital nurseries.
AB  - OBJECTIVE: To base permissible noise criteria for occupied, new nurseries on
      research findings. STUDY DESIGN: An interdisciplinary group of clinicians
      reviewed the literature regarding the effect of sound on the fetus, newborn, and
      preterm infant and based recommended criteria on the best evidence. An external
      panel subsequently reviewed the criteria. RESULTS: The recommended criteria:
      Patient bed areas and the spaces opening onto them shall be designed to produce
      minimal ambient noise and to contain and absorb much of the transient noise that
      arises within the nursery. The overall, continuous sound in any bed space or
      patient care area shall not exceed: (1) an hourly Leq of 50 dB and (2) an hourly
      L10 of 55 dB, both A-weighted, slow response. The 1-second duration Lmax shall
      not exceed 70 dB, A-weighted, slow response. CONCLUSION: The permissible noise
      criteria will protect sleep, support stable vital signs, and improve speech
      intelligibility for many infants most of the time.

PMID- 18818538
TI  - A descriptive study of noise in the neonatal intensive care unit: ambient levels
      and perceptions of contributing factors.
AB  - PURPOSE: To examine the baseline acoustic environment in several mid-Atlantic
      region neonatal intensive care units (NICUs) and investigate the perceived
      factors contributing to noise levels in these NICUs. SUBJECTS: Quantitative data
      were collected from 3 urban, mid-Atlantic level IIIB and level IIIC NICUs.
      Qualitative data were collected via interview from 2 RNs employed in each of the
      study NICUs. DESIGN: This was an exploratory descriptive study utilizing a mixed
      methods approach. A quantitative method was used for sound-level data collection,
      and a qualitative method was utilized during interviews with nurses to examine
      perceptions of factors contributing to noise. METHODS: Ambient sound levels,
      measured in decibels, were taken at 5-minute intervals over a 2-hour period
      during both day and night shifts in a central location at each NICU. In addition,
      nurses were interviewed using a standardized interview questionnaire, and these
      interviews were then reviewed to determine themes regarding perceived factors
      contributing to sound levels. MAIN OUTCOME MEASURES: Hourly mean sound levels in
      each NICU ranged from 53.9 dB to 60.6 dB, with no statistically significant
      difference between noise levels recorded on day shift versus night shift, and no
      statistically significant difference among sites. Qualitative data showed that
      nurses' believed day shift to be louder than night shift and many perceived their
      own NICU as "pretty quiet." Key contributing factors to increased sound levels
      were stated as monitors or alarms, performing invasive procedures, presence of
      family, nurses or doctors giving report or rounds, and ringing phones. PRINCIPAL
      RESULTS: Noise levels were found to be above the American Academy of Pediatrics
      recommended 45-dB level and often louder than the 50-dB level, which should not
      be exceeded more than 10% of the time. The recommended impulse maximum of 65 dB
      was also exceeded. Environmental Protection Agency recommendations for hospitals
      include sound levels no louder than 35 dB on night shift; this standard was also
      violated. CONCLUSIONS: Elevated sound levels need to be addressed in individual
      NICUs around the country. Further exploratory studies, as well as research
      regarding effective methods of decreasing sound levels in the NICU environment,
      are necessary. NICUs can implement behavioral and structural changes that can
      decrease the sound levels in the NICU environment and decrease the potential for
      exposure of patients to the harmful physiological effects of increased sound
      levels.

PMID- 18818539
TI  - Addressing noise in the NICU. Forward.

PMID- 18818541
TI  - Turn down the noise. 2008.

PMID- 18818542
TI  - Effect of environmental changes on noise in the NICU.
AB  - PURPOSE: To evaluate die effect of changes in die NICU environment on sound
      levels. DESIGN: A prospective quasi-experimental design evaluated sound levels in
      a 43-bed NICU. Decibel levels were monitored utilizing a data-logging dosimeter
      for 24 hours weekly over 12 months. Sound levels were also measured inside four
      different incubator models. SAMPLE: Forty-four 24-hour decibel recordings were
      obtained in one of eight randomly selected four-bed pods. In addition, a single 1
      hour recording was obtained in four different models of vacant incubators. MAIN
      OUTCOME VARIABLE: Ambient sound levels. RESULTS: Decibel levels were analyzed to
      identify changes in noise levels following alterations in the NICU environment.
      Installation of motion-sensing motorized paper towel holders significantly
      increased levels at beds closest to the towel dispensers, as did the trial of a
      new communication system. Decibel levels in four different incubators revealed
      varying noise levels. This study suggests that all environmental changes must be
      monitored to ensure that they reduce rather than increase noise levels.

PMID- 18818543
TI  - Success of five stapes prostheses evaluated by Kaplan-Meier product-survival
      procedure.
AB  - OBJECTIVE: To determine if modifications to a first-generation Teflon-wire piston
      stapes prosthesis improve results over time. STUDY DESIGN: Retrospective chart
      review. SETTING: Private practice. PATIENTS: Three hundred eleven ears in 277
      consecutive patients who had primary stapedotomies with reconstruction to an open
      fenestra during 1989 to 2000 and in 2005 to 2006. INTERVENTION: The devices were
      examined sequentially as follows: Schuknecht piston (50), De La Cruz piston (30),
      Mangham piston (179), titanium CliP piston (32), and Teflon Robinson prosthesis
      (20). MAIN OUTCOME MEASURES: American Academy of Otolaryngology-Head and Neck
      Surgery guidelines including 4-frequency pure-tone average, success rate (gap
      </=10 dB), and Kaplan-Meier product-survival procedure. RESULTS: When success was
      defined as an air-bone gap of 10 dB or less and no revision surgery for other
      reasons, patients with Schuknecht, De La Cruz, and Mangham pistons had comparable
      results; both at 1 year (87-96%) and in the long term (about 80% at 15 yr). The
      estimated median duration of success was 24 years. Success over time was
      significantly poorer for the Robinson prosthesis (76% at 1 year) and CliP piston,
      68% at 30 months (p < 0.05). Of 18 patients with crimpable pistons who had
      revision surgery, two-thirds had a finding of necrosis on the vestibular side of
      the incus. All 3 of the CliP piston patients with revisions had an unstable
      connection to the incus. CONCLUSIONS: Four second-generation prostheses-De La
      Cruz, Mangham, CliP, and Teflon-Robinson-all failed to improve on the success of
      a first-generation Schuknecht piston. The findings may apply only to the
      technique of sealing the fenestra after placing the prosthesis.

PMID- 18818544
TI  - TORP-vibroplasty: a new alternative for the chronically disabled middle ear.
AB  - OBJECTIVE: Surgery can often eradicate chronic middle ear disease in patients
      with recurrent cholesteatoma, tubal dysfunction, and others; however, in many
      cases, social hearing cannot be restored even after multiple revision
      tympanoplasties. A hearing aid is then recommended. Placement of an implantable
      hearing aid with its advantage of an unoccluded ear canal, irrespective of middle
      ear function, seems to be a promising alternative. STUDY DESIGN: After
      establishing the biomechanics of the ear in our temporal bone laboratory, various
      locations and attachments of a Vibrant transducer were investigated. These
      experiments resulted in the development of a new titanium clip holder for a
      Vibrant integrated total ossicular replacement prosthesis assembly with placement
      on the footplate. Four patients with permanent severe combined hearing loss were
      implanted with this device after multiple revision tympanoplasties. The first
      case is described in detail. RESULTS: Placing a transducer directly on the
      footplate via a rod transmission gave a better gain for the high frequencies than
      in the round window location. The acoustic results of the patients showed an
      improved gain in speech understanding, unobtainable by a conventional hearing
      aid. CONCLUSION: The concept of a total ossicular replacement prosthesis
      vibroplasty establishes a straightforward procedure in the tympanic cavity
      similar to a normal tympanoplasty. The open ear canal and its superior acoustic
      performance offer a promising perspective for revision operations in cases of
      incurable middle ear dysfunction.

PMID- 18818545
TI  - Biopolymer-released dexamethasone prevents tumor necrosis factor alpha-induced
      loss of auditory hair cells in vitro: implications toward the development of a
      drug-eluting cochlear implant electrode array.
AB  - HYPOTHESIS: Polymer-eluted dexamethasone (DXM) will retain its ability to protect
      against tumor necrosis factor alpha (TNFalpha)-induced hair cell (HC) loss.
      BACKGROUND: TNFalpha has been shown to be associated with trauma-induced hearing
      loss. DXM has been demonstrated to protect the cochlea against trauma-induced
      hearing loss. DXM is currently administered either systemically or locally to
      treat patients with sudden hearing loss of unknown cause. METHODS: P-3 organ of
      Corti explants challenged with an ototoxic level of TNFalpha was the experimental
      system, and the base form of DXM (DXMb) incorporated into a biorelease polymer
      (i.e., SIBS) was the otoprotection molecule tested. The efficacy of otoprotection
      was determined by counts of fluorescein isothiocyanate-phalloidin-stained HCs and
      changes in gene expression. RESULTS: HC counts show 1) SIBS alone did not protect
      HCs from TNFalpha ototoxicity (SIBS versus SIBS + TNFalpha; p < 0.001), and 2)
      SIBS with DXMb provides a significant level of protection against TNFalpha
      induced loss of HCs (TNFalpha + SIBS versus TNFalpha + SIBS/DXMb, 299 mug; p <
      0.001). Gene expression results show that polymer-eluted DXMb 1) upregulates
      antiapoptotic genes (i.e., Bcl-2, Bcl-xl) and downregulates a proapoptotic gene
      (i.e., Bax) in TNFalpha-challenged explants and 2) downregulates TNFR1 in these
      explants. CONCLUSION: Polymer-eluted DXMb retains its otoprotection capabilities
      in our in vitro test system of TNFalpha-challenged organ of Corti explants by
      altering the pattern of gene expression to favor survival of TNFalpha-exposed
      HCs. These results, although in vitro, support the application of polymer
      containing DXMb to electrode arrays for the conservation of hearing during
      cochlear implantation.

PMID- 18818546
TI  - Pulsatile tinnitus associated with internal carotid artery morphologic
      abnormalities.
AB  - OBJECTIVES: Internal carotid artery morphologic abnormalities mainly consist of
      tortuosities and coilings and can present with pulsatile tinnitus (PT). The
      purpose of this presentation is to report 3 representative cases and propose
      clinical and radiologic diagnostic criteria. PATIENTS: Three patients presenting
      with PT. INTERVENTION: Clinical evaluation including auscultation of the ear
      canal and head and neck. All patients underwent computed tomography angiography
      of the head and neck. MAIN OUTCOME MEASURES: Clinical evaluation, computed
      tomography angiography of the head and neck. RESULTS: Head bruit or objective
      tinnitus were detected in 2 patients. Symptoms of cerebral ischemia were absent.
      All patients were found to have tortuosities of the internal carotid arteries
      below the cranium base. One patient, in addition to tortuosity, had coiling as
      well. CONCLUSION: Morphologic abnormalities of the internal carotid artery may be
      associated with PT. Proper clinical evaluation coupled with computed tomography
      angiography of the head and neck can differentiate these abnormalities from other
      more serious vascular etiologies. Symptoms of cerebral ischemia warrant
      consultation with a vascular surgeon.

PMID- 18818548
TI  - Speech recognition and temporal amplitude modulation processing by Mandarin
      speaking cochlear implant users.
AB  - OBJECTIVES: Fundamental frequency (F0) information is important to Chinese tone
      and speech recognition. Cochlear implant (CI) speech processors typically provide
      limited F0 information via temporal envelopes delivered to stimulating
      electrodes. Previous studies have shown that English-speaking CI users' speech
      performance is correlated with amplitude modulation detection thresholds (AMDTs).
      The present study investigated whether Chinese-speaking CI users' speech
      performance (especially tone recognition) is correlated with temporal processing
      capabilities. DESIGN: Chinese tone, vowel, consonant, and sentence recognition
      were measured in 10 native Mandarin-speaking CI users via clinically assigned
      speech processors. AMDTs were measured in the same subjects for 20- and 100-Hz
      amplitude modulated (AM) stimuli presented to a middle electrode at five
      stimulation levels that spanned the dynamic range. To further investigate the CI
      users' sensitivity to temporal envelope cues, AM frequency discrimination
      thresholds (AMFDTs) were measured for two standard AM frequencies (50 and 100
      Hz), presented to the same middle electrode at 30% and 70% dynamic range with a
      fixed modulation depth (50%). RESULTS: Results showed that AMDTs significantly
      improved with increasing stimulation level and that individual subjects exhibited
      markedly different AMDT functions. AMFDTs also improved with increasing
      stimulation level and were better with the 100-Hz standard AM frequency than with
      the 50-Hz standard AM frequency. Statistical analyses revealed that both mean
      AMDTs (averaged for 20- or 100-Hz AM across all stimulation levels) and mean
      AMFDTs (averaged for the 50-Hz standard AM frequency across both stimulation
      levels) were significantly correlated with tone, consonant, and sentence
      recognition scores, but not with vowel recognition scores. Mean AMDTs were also
      significantly correlated with mean AMFDTs. CONCLUSIONS: These preliminary
      results, obtained from a limited number of subjects, demonstrate the importance
      of temporal processing to CI speech recognition. The results further suggest that
      CI users' Chinese tone and speech recognition may be improved by enhancing
      temporal envelope cues delivered by speech processing algorithms.

PMID- 18818550
TI  - Undergraduate otolaryngology education in Canadian medical schools.
AB  - OBJECTIVES: To examine the quantity and nature of undergraduate otolaryngology
      instruction in the Canadian medical school system and to present the management
      of the undergraduate otolaryngology curriculum at the University of Toronto
      medical school with a yearly enrolment of 224 students. STUDY DESIGN: Survey
      questionnaire and narrative description. METHODS: A structured one-page survey
      was administered to the education directors of all 16 Canadian medical schools.
      The administration of core learning material, scheduling, patient encounter
      logging, and student and instructor evaluations with computerized, on-line
      systems at the University of Toronto was described. RESULTS: Rotations in
      otolaryngology were highly variable across medical schools. Mandatory rotations
      in otolaryngology were identified in only 6 of the 16 undergraduate curricula.
      The average length of clinical experience in schools with mandatory rotations was
      4.6 days. CONCLUSIONS: The majority of Canadian medical graduates complete their
      undergraduate training with minimal clinical experience in otolaryngology. There
      is a clear discrepancy between the quantity and perceived need for training. To
      provide a thorough and equitable exposure to otolaryngology, a curriculum with
      standardized lectures and evaluation procedures is required.

PMID- 18818551
TI  - The treatment for postirradiation otitis media with effusion: a study of three
      methods.
AB  - OBJECTIVE: To explore treatments for postirradiation otitis media with effusion
      (OME) in patients with nasopharyngeal carcinoma. STUDY DESIGN: This study is a
      prospective quasi-randomized clinical trial. METHODS: Ninety-six patients (135
      ears) with OME after the first course of radiotherapy for nasopharyngeal
      carcinoma were divided into three groups: simple auripuncture plus aspiration,
      tympanic membrane fenestration with cauterization, and myringotomy plus grommet
      insertion. Cure rates and incidences of complications were compared. RESULTS: Two
      deaths occurred. The other 94 patients (132 ears) finished a 2-year follow-up. In
      group 1, four ears (8.9%) were cured after the first treatment and 17 ears
      overall (37.8%) were cured by the end of the follow-up. Twenty ears (44.4%) had
      persistent fluid, two ears (4.4%) developed chronic suppurative otitis media, and
      five ears (11.1%) developed dry eardrum perforation. In group 2, seven ears
      (15.6%) were cured after the first treatment and 21 ears overall (46.7%) were
      cured by the end of the follow-up. Fourteen ears (31.1%) had persistent fluid,
      three ears (6.7%) developed chronic suppurative otitis media, and seven ears
      (15.6%) developed dry eardrum perforation. In group 3, eight ears (17.8%) were
      cured after the first treatment and 23 ears overall (51.1%) were cured by the end
      of the follow-up. Seven ears (15.6%) had persistent fluid, five ears (11.1%)
      developed chronic suppurative otitis media, three ears (6.7%) developed eardrum
      perforation with effusion, and five ears (11.1%) developed dry eardrum
      perforation. CONCLUSION: The methods each have advantages and disadvantages. We
      believe that a step by step approach should be used when choosing the treatment
      method for postirradiation OME. That is, first apply auripuncture plus
      aspiration, and then the other methods if this approach is inadequate. Enhanced
      local care after grommet insertion can effectively reduce the incidence of
      complications.

PMID- 18818552
TI  - Transcanal antrotomy.
AB  - OBJECTIVE/HYPOTHESIS: This study describes a transcanal antrotomy technique and
      highlights its advantages for removal of disease in the tympanum and antrum.
      STUDY DESIGN: Retrospective review of surgical cases using a transcanal antrotomy
      approach. METHODS: The author's database of major otological procedures was
      reviewed to identify cases in which a transcanal approach was utilized to remove
      disease confined to the tympanum-antrum. Cases in which disease progressed into
      the mastoid, requiring a postauricular approach were excluded. Patient
      demographics, ear pathology, surgical variables, postoperative variables, and
      audiometric data were recorded. Standard descriptive statistics were used to
      summarize demographic and clinical characteristics of study cases. Intraoperative
      video segments were recorded and edited to depict the operative technique.
      RESULTS: Transcanal antrotomy was performed on 47 patients (mean age = 38.7, 51%
      men, 49% women). Ossicular reconstruction was performed in 27 patients during
      initial surgery. Sculptured, interposed incus was used in 77.8% of cases. Average
      intraoperative time was 130 minutes (range = 79-166 min). No major complications
      occurred postoperatively. Follow-up ranged from 26 to 3,680 days (average = 922
      days). No patient had recurrent disease in the antrum. Closure of air-bone gap to
      within 20 dB occurred in 85% of cases. CONCLUSIONS: Transcanal antrotomy is a
      safe, efficacious, and minimally-invasive approach to remove disease from the
      middle ear and antrum. This approach allows for optimal exposure of the antrum
      and is less invasive than postauricular and endaural approaches. With transcanal
      antrotomy, second stage procedures can be avoided in many cases resulting in
      reduced costs and improved quality of life.

PMID- 18818553
TI  - Dexamethasone base conserves hearing from electrode trauma-induced hearing loss.
AB  - OBJECTIVE/HYPOTHESIS: Local treatment of the cochlea after electrode insertion
      trauma with dexamethasone base conserves hearing against trauma-induced loss.
      STUDY DESIGN: Laboratory animal study. METHODS: A guinea pig model of electron
      insertion trauma (EIT)-induced hearing loss (HL) used 44 guinea pigs sub-divided
      into four groups: 1) unoperated, controls (Controls, n = 44); 2) EIT, untreated
      (EIT, n = 15); 3) EIT plus artificial perilymph (EIT + AP, n = 15); and 4) EIT
      plus dexamethasone base (EIT + DXMb, n = 14). Cochleae that received EIT were
      randomly selected with contralateral, unoperated cochleae as internal controls.
      Auditory brainstem responses (ABRs) in response to 0.5 to 16 kHz pure tones were
      obtained before surgery, immediately after surgery (0 day), and on post-EIT days
      3, 7, 14, and 30. Hair cell counts were obtained from stained organ of Corti
      specimens from all four groups (n = 3/group). Data were analyzed using analysis
      of variance and a Tukey-Kramer honestly significant difference post hoc test with
      significance alpha set at <0.05 (hearing) and <0.001 (hair cells). RESULTS: There
      were significant differences (<0.05) between the ABR thresholds of unoperated
      (control) and contralateral operated (experimental) ears of EIT and of EIT + AP
      groups for all tested frequencies. There was no statistical difference (>0.05) in
      ABR thresholds in the EIT + DXMb versus control groups for 0.5 to 4 kHz tones.
      DXMb treatment protected hair cells from EIT-induced damage and loss while AP
      treatment did not. CONCLUSION: The absence of significant differences in hearing
      thresholds between the EIT + DXMb group and control ears in response to 0.5 to 4
      kHz tones demonstrates that DXMb is as effective as the aqueous form of
      dexamethasone in conserving hearing against EIT-induced loss.

PMID- 18818554
TI  - Trimethoprim-sulfamethoxazole for osteoarthritis caused by Staphylococcus aureus
      or Kingella kingae.

PMID- 18818555
TI  - Nitazoxanide treatment of Cryptosporidium parvum in human immunodeficiency virus
      infected children.

PMID- 18818556
TI  - Two-year outcomes of children on non-nucleoside reverse transcriptase inhibitor
      and protease inhibitor regimens in a South African pediatric antiretroviral
      program.
AB  - BACKGROUND: Few data exist on the efficacy of the limited regimens for children
      with HIV, which are available in sub-Saharan Africa. METHODS: Retrospective
      cohort study to evaluate the clinical and laboratory outcomes of 391 children who
      received protease inhibitor (PI) or non-nucleoside reverse transcription
      inhibitor (nNRTI)-containing highly active antiretroviral regimens (HAART) from a
      Cape Town clinic. Endpoints included CD4% and count, viral loads, weight-for-age
      Z score (WAZ), survival, drug changes, and loss to follow-up over 24 months. A
      generalized estimating equation population-averaged model was used to identify
      associations with virological suppression, and a log-rank test explored
      associations with survival. RESULTS: Overall, this cohort achieved a sustained
      doubling of median CD4% from baseline, steady increase of median WAZ, and
      survival of 91%, despite only 49% virologic suppression at 24 months. However,
      when analyzed according to regimen, PI-containing regimens had better virologic
      suppression at all time points. There were no differences in immunologic and
      growth endpoints between regimens or in survival. In a multivariate model
      predicting virologic suppression at any duration up to 24 months and adjusting
      for baseline CD4%, regimen, age, baseline WAZ, duration of HAART, and year of
      HAART initiation, nNRTI-based regimens (odds ratio [OR]: 0.38; 95% confidence
      interval [CI]: 0.19-0.77) and length of time on HAART were inversely associated
      with virologic suppression. Age (OR: 1.23 per year; 95% CI: 1.09-1.39) was
      positively associated with virologic suppression. CONCLUSIONS: The benefits of
      HAART are substantial in this setting, although PI regimens achieved greater
      virologic suppression than nNRTIs. Further exploration of regimens and dosing of
      antiretrovirals for children in these settings is needed.

PMID- 18818557
TI  - Association of human aryl hydrocarbon receptor gene polymorphisms with risk of
      lung cancer among cigarette smokers in a Chinese population.
AB  - BACKGROUND AND OBJECTIVE: Most of the carcinogenic effects of polycyclic aromatic
      hydrocarbons present in tobacco smoke are mediated by the aryl hydrocarbon
      receptor (AHR), a ligand-dependent transcription factor that regulates tobacco
      induced expression of carcinogen metabolic enzymes. We hypothesized that genetic
      variations in AHR might confer individual susceptibility to lung cancer. METHODS:
      Eight selected single-nucleotide polymorphisms in AHR were genotyped using the
      Illumina SNP genotyping BeadLab platform in a case-control study of 500 lung
      cancer patients and 517 cancer-free controls in a Chinese population. RESULTS: We
      found that significantly increased lung cancer risk was associated with
      heterozygous genotypes of rs2158041 (adjusted odds ratio=1.53 and 95% confidence
      interval=1.17-1.99 for GA, compared with the GG genotype) and rs7811989 (adjusted
      odds ratio=1.48 and 95% confidence interval=1.13-1.93 for GA, compared with the
      GG genotype), although these two single-nucleotide polymorphisms were in linkage
      disequilibrium. Furthermore, haplotype analysis revealed significant differences
      in haplotype distributions of AHR between cases and controls (Global P=1.38e-5).
      We also observed statistically significant interaction between the polymorphism
      rs2066853 (p.Arg554Lys) and cumulative cigarette smoking as a discrete or
      continuous variable (P=0.033 and 0.019, respectively), and the Lys/Lys genotype
      conferred an increased risk of lung cancer in the heavy smokers (adjusted odds
      ratio=3.36 and 95% confidence interval=1.07-10.55). CONCLUSION: These findings
      suggest that AHR polymorphisms and potential gene-smoking interaction may be
      involved in the etiology of lung cancer. Further large prospective studies with
      ethnically diverse populations and functional studies are warranted to validate
      these findings.

PMID- 18818558
TI  - Investigating the safety of electroacupuncture with a Picoscope.
AB  - Our wish to know more about the paths taken by electrical currents in
      electroacupuncture (EA) with special reference to the heart, particularly in
      patients with an implanted pacemaker, prompted us to undertake this study. Using
      ourselves as subjects, we have developed a safe oscillographic method to detect,
      visualise and record the EA currents that avoids the use of equipment requiring
      mains electricity. After two trials with unsatisfactory equipment, we found that
      the newly developed model 3425 PicoScopeTM (Pico Technology Ltd), with a four
      channel differential amplifier input connected to a laptop PC operating in
      battery mode, satisfied our criteria. With this recording system, we carried out
      two sets of experiments in which EA was provided by a Cefar acus4TM stimulator.
      The results confirm that the placement of a pair of acupuncture needles for EA
      can be used to predict the paths taken by the stimulating currents, and thus
      their areas of likely influence. When the needles are placed in closely adjacent
      acupuncture points in a limb, there is little or no detectable spread of the
      currents along the limb or into the chest. By contrast, when the needles are
      placed far apart, the electrical currents spread widely. Thus, when each of a
      pair of needles is placed in a point on opposite arms, the electrical currents
      recorded in the area of the pectoral muscles is of an order that might trigger an
      abnormal cardiac rhythm in a susceptible heart or activate a cardiac pacemaker
      incorporating an intracardiac defibrillator (ICD). Our results confirm the
      guidelines for EA safe practice recommended by the British Medical Acupuncture
      Society (BMAS) to avoid adverse events, ie EA should not be applied such that the
      current is likely to traverse the heart. We can now be confident that electric
      fields generated by pairs of needles below the knee or elbow do not create
      detectable currents in the chest. It is likely that similar results would be
      obtained with the use of transcutaneous electrical nerve stimulation (TENS) but
      this remains to be established by additional experiments.

PMID- 18818559
TI  - Pudendal nerve electroacupuncture for lumbar spinal canal stenosis - a case
      series.
AB  - OBJECTIVE: To investigate the effectiveness of pudendal nerve electroacupuncture
      for lumbar and lower limb symptoms in patients with lumbar spinal canal stenosis
      for whom acupuncture of the lumbar and lower limb muscles had been ineffective.
      METHODS: Nine patients with lumbar spinal canal stenosis for whom conventional
      acupuncture at the lumbar and lower limb muscles had no effect. Pudendal nerve
      electroacupuncture was performed eight times (once per week). VAS scores and
      continuous walking distance were used to evaluate changes in symptoms. RESULTS:
      The following changes in symptoms occurred after pudendal nerve
      electroacupuncture: low back pain was improved from 45.3+/-17.4mm (mean +/- SD)
      to 39.2+/-14.0mm, lower limb pain was improved from 61.1+/-5.6mm to 35.4+/
      11.9mm, lower limb dysaesthesia was improved from 63.9+/-8.4mm to 46.9+/-16.2mm,
      and continuous walking distance was improved from 100.0+/-35.4m to 250.0+/
      136.9m. Conclusion Pudendal nerve electroacupuncture may be an effective
      treatment for lumbar and lower limb symptoms due to spinal canal stenosis, and is
      potentially useful in patients who have not responded to conventional
      acupuncture.

PMID- 18818560
TI  - The effect of electrical stimulation of the pudendal nerve on sciatic nerve blood
      flow in animals.
AB  - OBJECTIVE: To investigate the mechanism of the clinical effect of
      electroacupuncture of the pudendal nerve on the lumbar and lower limb symptoms
      caused by lumbar spinal canal stenosis, we studied changes in sciatic nerve blood
      flow during electrical stimulation of the pudendal nerve in the rat. METHODS
      Using rats (n=5), efferent electrical stimulation to the pudendal nerve was
      performed and sciatic nerve blood flow was measured with laser Doppler flowmetry.
      Simultaneously, changes in the blood pressure and cardiac rate were measured.
      Furthermore, the effect of atropine on these responses to the stimulation was
      also studied. RESULTS: Electrical stimulation of the pudendal nerve significantly
      increased blood flow in the sciatic nerve transiently without increasing heart
      rate and systemic blood pressure. The significant increase in the sciatic nerve
      blood flow disappeared after administration of atropine. CONCLUSION: Electrical
      stimulation of the pudendal nerve causes a transient and significant increase in
      sciatic nerve blood flow. This response is eliminated or attenuated by
      administration of atropine, indicating that it occurs mainly via cholinergic
      nerves.

PMID- 18818561
TI  - Effects of manual acupuncture with sparrow pecking on muscle blood flow of normal
      and denervated hindlimb in rats.
AB  - INTRODUCTION: In clinical practice, it has been thought that acupuncture might
      serve to wash out pain-generating metabolic end-products by improving blood
      circulation in muscles. We investigated the effects of manual acupuncture (MA) on
      muscle blood flow (MBF) of normal and denervated hindlimbs in rats. METHOD:
      Sprague-Dawley rats (n=100) anaesthetised with urethane (1.2g/kg ip) were used.
      Manual acupuncture with sparrow pecking (SP) at different doses (1, 10 or 30
      pecks) was given to the right ventral hindlimb muscles (tibial anterior and
      extensor digitorum longus muscles) or the right dorsal hindlimb muscles
      (gastrocnemius, plantaris and soleus muscles). MBF with or without MA was
      measured using the radiolabelled microsphere technique. The blood pressure was
      recorded through the right common carotid artery until MBF measurement started.
      Denervation of hindlimb was conducted by cutting the sciatic and femoral nerves.
      RESULTS: In normal rats, significantly increased MBF after MA were observed only
      in muscles which were penetrated by an acupuncture needle. The size of the
      increase depended on the number of times of pecking and seemed to be sustained at
      least until 60 minutes after MA. However, the increase was observed after both
      acute and chronic denervation. On the other hand, the mean arterial blood
      pressure (MAP) did not change significantly before, during or after MA.
      CONCLUSION: These results suggest that MA could increase muscle blood flow
      locally in a dose-dependent manner and that this increase may be caused by local
      vasodilators, as well as the axon reflex. A further study is needed to elucidate
      the mechanism.

PMID- 18818562
TI  - Magnets applied to acupuncture points as therapy - a literature review.
AB  - OBJECTIVES: To summarise the acu-magnet therapy literature and determine if the
      evidence justifies further investigation of acu-magnet therapy for specific
      clinical indications. METHODS: Using various search strategies, a professional
      librarian searched six electronic databases (PubMed, AMED, ScienceDirect College
      Edition, China Academic Journals, Acubriefs, and the in-house Journal Article
      Index maintained by the Oregon College of Oriental Medicine Library). English and
      Chinese language human studies with all study designs and for all clinical
      indications were included. Excluded were experimental and animal studies,
      electroacupuncture and transcranial magnetic stimulation. Data were extracted on
      clinical indication, study design, number, age and gender of subjects, magnetic
      devices used, acu-magnet dosing regimens (acu-point site of magnet application
      and frequency and duration of treatment), control devices and control groups,
      outcomes, and adverse events. RESULTS: Three hundred and eight citations were
      retrieved and 50 studies met our inclusion criteria. We were able to obtain and
      translate (when necessary) 42 studies. The language of 31 studies was English and
      11 studies were in Chinese. The 42 studies reported on 32 different clinical
      conditions in 6453 patients from 19862007. A variety of magnetic devices, dosing
      regimens and control devices were used. Thirty seven of 42 studies (88%) reported
      therapeutic benefit. The only adverse events reported were exacerbation of hot
      flushes and skin irritation from adhesives. CONCLUSIONS: Based on this literature
      review we believe further investigation of acu-magnet therapy is warranted
      particularly for the management of diabetes and insomnia. The overall poor
      quality of the controlled trials precludes any evidence based treatment
      recommendations at this time.

PMID- 18818563
TI  - Effects of minimal acupuncture in children with infantile colic - a prospective,
      quasi-randomised single blind controlled trial.
AB  - BACKGROUND: Colic causes crying in 10-30% of infants and is one of the primary
      reasons parents seek health care. Treatments are generally not totally effective
      and some cause side effects. In this study we aimed to test the effect of light
      needling (minimal acupuncture) on crying. METHODS: Forty children (median six
      weeks of age) with excessive crying unresponsive to conventional therapies, were
      recruited from 21 Child Welfare Clinics within an area of western Sweden, and
      quasi-randomised to control or light needling treatment. Parents were unaware of
      which group their child was assigned to. Children were given light needling
      acupuncture on one point (LI4) on both hands for approximately 20 seconds on four
      occasions, or received the same care except needling. Parental assessment
      questionnaires were used pre- and post-treatment to assess crying intensity,
      frequency, duration of crying and pain related behaviour throughout the day in
      six hour periods. RESULTS: Light needling resulted in a significant reduction in
      the rated crying intensity (assessed by a numeric rating scale, 0 to 10). For
      example, during the morning time period 0600-1200 hours, the median (range) rated
      crying intensity changed from 6 (1 to 9) pre-treatment to 2 (0 to 5) post
      treatment (P=0.002), in the light needling group. The corresponding ratings for
      the children in the control group was 6 (0 to 10) and 5 (0 to 10) respectively.
      The difference between the groups was significant (P=0.016). There were also
      significant differences between the groups for the afternoon (1200-1800 hours),
      and evening (1800-midnight) time periods. Pain related behaviour like facial
      expression, was also significantly less pronounced in the light needling group as
      compared to the control group post-treatment, (P=0.027). The parents rated the
      light needling as more effective in improving symptoms than the control group
      (P<0.001). CONCLUSION: Four treatments with light needling on one point in the
      hand may alleviate crying and pain related behaviour without any noted side
      effects.

PMID- 18818564
TI  - Setting up an acupuncture knee clinic under Practice Based Commissioning.
AB  - This paper outlines the setting up of a new service in primary care offering
      acupuncture to patients with severe osteoarthritis of the knee. The high volume
      clinic is funded under the Practice Based Commissioning initiative and is the
      first of its type in the UK. It appears to offer a model for similar services
      elsewhere.

PMID- 18818565
TI  - Acupuncture for back pain, knee pain and insomnia in transverse myelitis - a case
      report.
AB  - This case report describes the use of acupuncture for back pain, knee pain and
      insomnia in a 49 year old woman with a recent diagnosis of transverse myelitis
      with paraplegia, sensory disturbance, and bladder and bowel dysfunction. She was
      receiving intensive in-patient multi-disciplinary rehabilitation but was
      struggling to participate fully due to pain and poor sleep quality. She received
      a course of acupuncture in addition to standard care and reported substantial
      benefits including reduction in pain, improved sleep and mood, and reduction in
      daytime fatigue. Effective symptom control allowed this patient to participate
      more fully in her rehabilitation programme. Reduction of knee pain and sleep
      disturbance was maintained until discharge, 15 weeks after the last acupuncture
      treatment. This case report suggests that acupuncture may be an option to
      consider for other patients with pain or sleep disturbance that is interfering
      with their rehabilitation programme.

PMID- 18818566
TI  - Acupuncture induced pneumothorax - a case report.
AB  - We report a significant complication of acupuncture in a 50 year old woman who
      developed a pneumothorax shortly after receiving acupuncture needling to her
      scapulothoracic region in a lateral oblique direction. As acupuncture is
      increasingly being used in pain management, physicians need to be aware of its
      potential adverse effects. We discuss issues relating to appropriate counselling
      of patients receiving this form of therapy. The inner Bladder line should be
      needled obliquely towards the spine.

PMID- 18818567
TI  - Computer-assisted surgical systems in cardiothoracic surgery: why are we
      reluctant to accept the future?

PMID- 18818568
TI  - Reexpansion pulmonary edema.
AB  - When a rapidly reexpanding lung has been in a state of collapse for more than
      several days, pulmonary edema sometimes occurs in it. This is called reexpansion
      pulmonary edema (RPE). In this article, I present my views on the history,
      clinical features, morphophysiological features, pathogenesis, and treatment of
      RPE. Histological abnormalities of the pulmonary microvessels in a chronically
      collapsed lung will cause RPE, as well as mechanical stress exerted during
      reexpansion. Although the most effective treatment method is to treat the
      histological abnormalities of the pulmonary microvessels formed in a chronically
      collapsed lung, the cause of these abnormalities is not clear, making it
      difficult to put forward a precise treatment method. However, reasonably good
      effects can be expected from a symptomatic therapy that reduces the level of
      mechanical stress during reexpansion. In the future, it is expected that the
      cause of histological changes of the pulmonary microvessels in a chronically
      collapsed lung will be revealed, and appropriate therapies will therefore be
      developed according to this cause.

PMID- 18818569
TI  - Increased superoxide radical with a decrease in vascular endothelial growth
      factor and inducible nitric oxide synthase level leads to the progression of left
      ventricular hypertrophy in a pressure-overload rat heart model.
AB  - PURPOSE: This study was designed to evaluate the relationship among free radicals
      and vascular endothelial growth factor (VEGF) and inducible nitric oxide synthase
      (iNOS) during the progression of left ventricular hypertrophy (LVH) in pressure
      overload rat heart. METHODS: Hypertrophied rat heart created by abdominal aortic
      banding at the age of 4 weeks was studied at the ages of 14, 15, 18, 21, 26, and
      30 weeks (n=5 in each group). Free radicals were detected by an electron spin
      resonance (ESR) method using LV tissue. The levels of messenger ribonucleic acid
      (mRNA) for VEGF, superoxide dismutase (SOD), and iNOS in myocardium were analyzed
      by reverse transcription (RT)-polymerase chain reaction (PCR). RESULTS: Free
      radicals consisting of superoxide families increased over time after aortic
      banding and were highest in the 30-week group. The SOD mRNA level decreased with
      the progression of hypertrophy and was inversely proportional to the free
      radicals level. As compared to the control, the level of mRNA for VEGF and iNOS
      was significantly increased in 18-and 21-week hypertrophied hearts, but
      significantly decreased in 26-and 30-week hearts. CONCLUSION: The increased level
      of free radicals with the decrease of VEGF and iNOS levels may contribute to the
      progression of the pressure-overload hypertrophied heart to the failing heart.

PMID- 18818570
TI  - Analyzing the outcome of early versus prolonged extubation following cardiac
      surgery.
AB  - OBJECTIVES: This study considered the factors associated with prolonged
      ventilation and the effects of reduced extubation times on patient recovery,
      intensive care unit stay, and overall hospital stay. MATERIALS AND METHODS: A
      retrospective study was performed, including 86 consecutive patients who
      underwent cardiac surgery from August 2006 to January 2007. The patients were
      divided into two groups following intensive care unit admission: Group A,
      duration of intubation <4 h (n=34); Group B, duration of intubation >4 h (n=52).
      RESULTS: Two deaths occurred in 86 patients, and overall hospital mortality was
      2.32%. Patients in Group A were younger (33.2+/-12 versus 45.8+/-13 years;
      p=0.001) and had better preoperative left ventricular ejection fraction (LVEF)
      (62.4+/-9.8 versus 44.6+/-9.4; p=0.003) than those in Group B. Moreover, Group A
      patients had a shorter intensive care unit length of stay (1.7+/-0.5 versus 2.2+/
      0.8 days; p=0.006) and were discharged earlier than Group B patients (2.7+/-2.4
      versus 4.01+/-3.96; p=0.014). CONCLUSIONS: Early extubation offers a substantial
      advantage in terms of accelerated recovery, shorter intensive care unit, and
      hospital stay, suggesting that efforts to reduce extubation times are cost
      effective.

PMID- 18818571
TI  - Effect of aspirin on postoperative bleeding in coronary artery bypass grafting.
AB  - PURPOSE: It is not uncommon for aspirin therapy to be withheld before coronary
      artery bypass grafting (CABG) because it is thought to increase the risk of
      postoperative bleeding. Many studies have shown that continued aspirin therapy
      reduces postoperative myocardial infarction and increases survival. The purpose
      of this study is to analyze the effect of preoperative aspirin on postoperative
      bleeding in patients undergoing CABG. MATERIAL AND METHODS: Patients (n=30)
      undergoing CABG were divided into two groups, group 1 (n=15) who received aspirin
      till the day of surgery, and group 2 in whom aspirin was stopped 5 days before
      surgery. Postoperative bleeding up to 76 h (approximately 3 days) was noted in
      both groups. RESULTS: Preoperative, intraoperative, and postoperative variables
      were equal in both groups. Postoperative bleeding in the 2nd hour was
      significantly lower in group 1 compared to group 2 (p=0.004). Bleeding 28-76 h
      postoperatively was also significantly lower in the first group (p=0.043).
      CONCLUSION: Our study suggests that contrary to the commonly held beliefs in our
      setup, the use of aspirin till the date of surgery does not increase the risk of
      postoperative bleeding after CABG. In contrast, our data show reductions in the
      bleeding incidence of those in whom aspirin was not withheld prior to surgery.
      Therefore we strongly recommend its continued use of aspirin until the date of
      surgery.

PMID- 18818572
TI  - Inhibition of platelet aggregation by combined therapy with aspirin and
      cilostazol after off-pump coronary artery bypass surgery.
AB  - BACKGROUND: Although off-pump coronary artery bypass (OPCAB) has become an
      increasingly common surgical procedure, recent concerns have been raised
      regarding the existence of a hypercoagulable or prothrombotic state associated
      with OPCAB. To determine the optimal antiplatelet regimen after OPCAB, we
      investigated the effects of aspirin alone and of combined therapy with aspirin +
      cilostazol on platelet aggregation in patients after OPCAB. MATERIAL AND METHODS:
      Twenty patients scheduled to undergo OPCAB were randomized to one of two
      antiplatelet regimens: aspirin alone (n=10) and aspirin + cilostazol (n=10). Anti
      platelet agents had not been received for at least 1 week before surgery and were
      initiated on the afternoon of postoperative day 1. Platelet aggregability and
      hemostatic parameters were evaluated at four time points: before and 3, 7, and 14
      days after OPCAB. We measured agonist-and shear stress-induced platelet
      aggregation (SIPA) using a modified cone-plate viscometer. RESULTS: No
      complications resulting from postoperative antiplatelet therapy-related bleeding
      were seen in either group. Collagen-and arachidonate-induced platelet aggregation
      and SIPA were significantly inhibited in the aspirin + cilostazol group compared
      with the aspirin-alone group (collagen-and arachidonate-induced aggregation,
      p<0.0001; SIPA, p=0.0367). Adding cilostazol to aspirin augmented the inhibitory
      effects on platelet aggregation induced by collagen and arachidonate. adenosine
      diphosphate (ADP)-induced platelet aggregation tended to be inhibited in the
      aspirin + cilostazol group compared with the aspirin-alone group (p=0.0534).
      CONCLUSION: The results of this study suggest that combined therapy with aspirin
      + cilostazol is more effective than aspirin monotherapy in reducing platelet
      aggregation in patients after OPCAB. This combination therapy may represent a new
      therapeutic option for an anti-thrombotic regimen in patients after OPCAB.

PMID- 18818573
TI  - Penile metastasis from esophageal squamous carcinoma after curative resection.
AB  - The penis is an uncommon site of metastasis; with only about 300 cases reported
      in literature. The majority (75%) of primary tumors are located in the pelvis,
      and they arise from the genitourinary tract and rectum. We report on a patient
      with esophageal squamous carcinoma who underwent a curative resection and later
      developed metastatic nodules over the penis and perineum. We believe this is the
      first instance of this unusual presentation. He was offered palliation with
      weekly taxanes and had symptomatic relief with this regimen.

PMID- 18818574
TI  - Squamous cell carcinoma of the hilar lymph node with unknown primary tumor: a
      case report.
AB  - We herein report a rare case of squamous cell carcinoma (SCC) located in the
      hilar nodes with unknown primary tumor. A 56-year-old man underwent a thoracotomy
      under the clinical diagnosis of lung cancer with hilar nodes involvement. The
      tumor was found at the hilus and resected without pulmonary resection. The
      pathological diagnosis of this tumor was metastatic SCC in hilar lymph nodes.
      Examinations of the whole body failed to detect a primary site of the SCC. The
      patient is doing well with no clinical sign of recurrence 32 months after
      surgery.

PMID- 18818575
TI  - Malignant peripheral nerve sheath tumor with Horner's syndrome: a case report.
AB  - We report on a 42-year-old woman with malignant peripheral nerve sheath tumor
      (MPNST) arising from the cervical sympathetic nerve. A collar incision and
      partial sternotomy were performed at the second intercostal space. The mass was
      spindle shaped and connected to the sympathetic trunk on the cranial and caudal
      sides, and it compressed the left carotid sheath on the median side. After the
      patient's uneventful recovery from surgery, adjuvant radiotherapy was
      administered to the area of resection. The patient remains well 5 years after
      surgery with no evidence of recurrence.

PMID- 18818576
TI  - Mucoid impaction after segmental resection of lung.
AB  - Lung segmentectomy is generally considered as a standard procedure in general
      thoracic surgery. Anatomical variations of pulmonary segmentation may, however,
      make it difficult to determine the precise area of resection during
      segmentectomy. Incomplete pulmonary sub-lobar resection may produce unusual
      radiographic features. Herein, we report a case of bronchial atresia after lung
      segmentectomy.

PMID- 18818577
TI  - Reasonable and effective volume reduction of a giant left atrium associated with
      mitral valve disease.
AB  - Severe left atrial enlargement associated with mitral valve disease has been
      known to carry a poor prognosis in patients undergoing mitral valve repair or
      replacement. There are several reasons why left atrial size can have a
      significantly negative impact on prognosis. A giant left atrium (LA) can cause
      postoperative respiratory dysfunction by bronchial and pulmonary compression and
      hemodynamic disturbance subsequent to compression of the posterobasal portion of
      the left ventricle (LV). Moreover, the presence of a giant LA can increase
      thromboembolic risk despite anticoagulant therapy after operation. We report a
      case of a 62-year-old female who had a markedly enlarged LA associated with
      mitral valve stenosis and regurgitation. The patient, who had severely
      restrictive and obstructive respiratory dysfunction, underwent mitral valve
      replacement and left atrial volume reduction with postoperative improvement in
      hemodynamic and respiratory function. We believe that volume reduction of an
      enlarged LA, in addition to mitral valve surgery, is important not only because
      it leads to improvement in heart failure but also because it will relieve
      compression of the adjacent organs.

PMID- 18818578
TI  - Patent ductus arteriosus with hemiazygos communication to left superior vena
      cava.
AB  - We experienced the ligation of patent ductus arteriosus (PDA) via the left
      thoracotomy in a 24-day-old infant with inferior vena cava defect and hemiazygos
      communication to a persistent left superior vena cava (LSVC). Although the large
      hemiazygos vein (HAzV) crossed just in front of PDA, its mobilization enabled the
      smooth ligation of PDA without hemodynamic instability. The postoperative course
      was uneventful.

PMID- 18818579
TI  - Septal myectomy, papillary muscle resection, and mitral valve replacement for
      hypertrophic obstructive cardiomyopathy: a case report.
AB  - We report a case of hypertrophic obstructive cardiomyopathy (HOCM) successfully
      treated with septal myectomy and mitral valve replacement (MVR) combined with a
      resection of the hypertrophic papillary muscles. The patient, a 74-year-old
      woman, first underwent the conventional septal myectomy through aortotomy. The
      papillary muscles revealed a marked hypertrophy, but extended myectomy and
      precise resection of the hypertrophic papillary muscles were thought to be
      difficult through the aortotomy. Through the right-sided left atriotomy, MVR and
      resection of the papillary muscles were additionally performed. The patient was
      smoothly weaned from the cardiopulmonary bypass, and the postoperative course was
      uneventful. The outflow pressure gradient was relieved to 0 mm Hg, from 94. The
      mean pulmonary artery pressure was reduced to 27 mm Hg, from 42. The patient has
      been doing well in the New York Heart Association (NYHA) functional class between
      I and II during 45 months of follow-up, without complications related to the use
      of a prosthetic valve. Septal myectomy is the procedure of choice in the surgical
      treatment of HOCM for most cases, but some may require additional mitral valve
      procedures. In patients with marked hypertrophic papillary muscles, MVR and
      resection of the muscles may be an option of treatment to ensure a relief of the
      outflow obstruction and to abolish systolic anterior movement in units with
      limited experience.

PMID- 18818580
TI  - Extensive patch angioplasty of the left main ostial stenosis using a rhombic
      shaped pulmonary autograft.
AB  - A rhombic shaped pulmonary autograft patch was applied to enlarge an ostial
      stenosis of the left main coronary artery (LMCA) in a 25-year-old woman diagnosed
      with vasculitis syndrome. The patch increased the width of the ostial stenosis
      and made a funnel-shaped connection. At eighteen months of follow-up, a coronary
      angiogram by computed tomography showed no restenosis at the LMCA. The rhombic
      shaped pulmonary autograft patch might be an ideal shape and material for
      angioplasty of the ostial stenosis of the LMCA.

PMID- 18818581
TI  - An aneurysm at the cannulation site discovered 40 years after cardiac surgery:
      report of a case.
AB  - We report the successful surgical treatment of a pseudoaneurysm of the ascending
      aorta in a 45-year-old man who underwent surgical closure of a ventricular septal
      defect at the age of 5. A computed tomography scan ordered for the investigation
      of a pulmonary mass happened to detect a pseudoaneurysm (20 mm diameter). The
      pseudoaneurysm protruded anteriorly from the ascending aorta at the previous
      aortic cannulation site. The ascending aorta, including the lesion, was replaced
      with a prosthetic graft uneventfully. The cause of the pseudoaneurysm was
      considered iatrogenic, since he had no prior history of postoperative
      mediastinitis or blunt chest trauma. A computed tomography scan is a useful means
      to detect a mass on the ascending aorta following cardiac surgery, and it
      provides important information to help define a surgical strategy.

PMID- 18818582
TI  - State-specific influenza vaccination coverage among adults--United States, 2006
      07 influenza season.
AB  - Adult groups included in the 2008 Advisory Committee on Immunization Practices
      (ACIP) recommendation for annual influenza vaccination include all persons aged
      >/=50 years, women who will be pregnant during the influenza season, persons aged
      18-49 years with high-risk conditions, and other persons at increased risk for
      complications from influenza. Health-care personnel and household contacts and
      caregivers of persons at high risk also should receive annual influenza
      vaccination, as should adults who want to reduce their risk for becoming ill with
      influenza or for transmitting it to others. Healthy People 2010 influenza
      vaccination coverage targets are 90% among all persons aged >/=65 years and 60%
      among persons aged 18-64 years who have one or more high-risk conditions. Data
      from the 2006 and 2007 Behavioral Risk Factor Surveillance System (BRFSS) surveys
      indicate that influenza vaccination coverage among adults for the 2006-07 season
      increased significantly compared with the 2005-06 season, reaching 35.1% among
      persons aged 18-49 years with high-risk conditions, 42.0% among all persons aged
      50-64 years, and 72.1% among all persons aged >/=65 years. However, vaccination
      coverage remained well below Healthy People 2010 targets. Increasing influenza
      vaccination coverage among adults in the United States will require more
      cooperation among health-care providers, professional organizations, vaccine
      manufacturers, and public health departments to raise public awareness about
      influenza vaccination and to ensure continued distribution and administration of
      available vaccine throughout the vaccination season.

PMID- 18818583
TI  - Influenza vaccination coverage among children aged 6-23 months--United States,
      2006-07 influenza season.
AB  - Children aged <5 years have more influenza-related medical-care visits compared
      with older children, and those aged <2 years are at the greatest risk for
      influenza-related hospitalizations. In 2002, the Advisory Committee on
      Immunization Practices (ACIP) encouraged annual influenza vaccination of children
      aged 6-23 months and then, in 2004, recommended vaccination for this group. Two
      doses, spaced at least 4 weeks apart, are recommended to fully vaccinate children
      aged <9 years who are receiving influenza vaccination for the first time. This
      report, based on data from the 2007 National Immunization Survey (NIS), provides
      an assessment of influenza vaccination coverage among children aged 6-23 months
      during September-December of the 2006-07 influenza season. Nationally, 31.8% of
      children received 1 or more doses of influenza vaccine, and 21.3% were fully
      vaccinated, with substantial variability among states. The findings underscore
      the need to increase interest in and access to influenza vaccination for more
      children in the United States. Further study is needed to identify knowledge
      deficits or logistical barriers that might contribute to continued low influenza
      vaccination coverage among young children.

PMID- 18818584
TI  - Influenza vaccination coverage among children aged 6-59 months--eight
      immunization information system sentinel sites, United States, 2007-08 influenza
      season.
AB  - Vaccination is the most effective way to prevent influenza-associated morbidity
      and mortality. However, influenza vaccination coverage among children
      historically has been low. The Advisory Committee on Immunization Practices
      (ACIP) recommends annual vaccination with influenza vaccine for all children aged
      6-59 months. Previously unvaccinated children and children who received only 1
      vaccine dose for the first time in the previous influenza season are recommended
      to receive 2 influenza vaccine doses. To assess vaccination coverage among
      children aged 6-59 months during the 2007-08 influenza season, CDC analyzed data
      from the eight immunization information system (IIS) sentinel sites. For the
      eight sites, an average (unweighted) of 40.8% of children aged 6-23 months
      received 1 or more influenza vaccine doses, and an average of 22.1% were fully
      vaccinated. Among children aged 24-59 months, an average of 22.2% received 1 or
      more doses, and an average of 16.5% were fully vaccinated. These results indicate
      that influenza vaccination coverage among children remains low and highlight the
      need to identify additional barriers to influenza vaccination and to develop more
      effective interventions to promote vaccination of children aged 6--59 months who
      are at high risk for influenza-related morbidity and mortality.

PMID- 18818585
TI  - Influenza activity--United States and worldwide, May 18-September 19, 2008.
AB  - During May 18-September 19, 2008, influenza A (H1), influenza A (H3), and
      influenza B viruses were detected worldwide and were identified sporadically in
      the United States. This report summarizes influenza activity in the United States
      and worldwide since the last update and reviews the new influenza vaccine
      recommendations for the upcoming season. Influenza viruses circulating this
      summer appear antigenically similar to the strains included in the 2008-09
      influenza vaccine. Recent antiviral resistance data are limited, but oseltamivir
      resistance among influenza A (H1N1) viruses might persist during the 2008-09
      influenza season.

PMID- 18818586
TI  - Progress toward measles elimination--Japan, 1999-2008.
AB  - In 2005, the Regional Committee of the World Health Organization (WHO) Western
      Pacific Region (WPR) set a target date of 2012 for measles elimination in all WPR
      member states. In Japan, measles control strategies have included 1) a nationwide
      public awareness campaign implemented in 2001 to promote timely vaccination with
      the first dose of measles-containing vaccine (MCV1) administered on or after age
      12 months, and 2) a 2-dose MCV schedule with the second dose (MCV2) administered
      at age 5-6 years, adopted in 2006 in accordance with the recommended WPR measles
      elimination strategy. However, during 2007-2008, Japan experienced a large
      measles outbreak, which resulted in exportation of measles cases from Japan into
      countries where measles elimination had been achieved. This report describes the
      epidemiology of measles in Japan during 1999--2008 and approval of a National
      Measles Elimination Plan in December 2007 that includes recommendations for
      immunization strategies, case-based measles surveillance, and monitoring to
      ensure elimination of measles by 2012. Measles continues to be endemic in Japan,
      with most cases occurring in children before school entry, except for 2007 and
      2008, when a shift to an older age group was observed. With implementation of the
      National Measles Elimination Plan, Japan is expected to make progress toward
      achieving the WPR measles elimination goal.

PMID- 18818588
TI  - No science left behind.

PMID- 18818590
TI  - Right way neurons.

PMID- 18818591
TI  - FoxP1: conducting the Hox symphony in spinal motor neurons.

PMID- 18818592
TI  - Regenerating your senses: multiple roles for neurogenesis in the adult brain.

PMID- 18818593
TI  - Pavlov's moth: olfactory learning and spike timing-dependent plasticity.

PMID- 18818597
TI  - Creation and classrooms.

PMID- 18818598
TI  - America's fresh start.

PMID- 18818599
TI  - Pathways to security.

PMID- 18818611
TI  - LHC meltdown before first collision.

PMID- 18818612
TI  - California institute to help stem-cell biotechs.

PMID- 18818613
TI  - Monoclonal antibodies come of age.

PMID- 18818614
TI  - Gulf states plan for nuclear future.

PMID- 18818615
TI  - Brazil braced for unexpected oil wealth.

PMID- 18818623
TI  - US election: The home stretch.

PMID- 18818624
TI  - US election: Questioning the candidates. Interview by Alexandra Witze.

PMID- 18818625
TI  - US election: Agencies of change.

PMID- 18818626
TI  - US election: Not the best advice.

PMID- 18818627
TI  - Science prizes: Best in class.

PMID- 18818628
TI  - Shaping science education in just 100 words.

PMID- 18818629
TI  - Animal research: too much faith in models clouds judgement.

PMID- 18818630
TI  - Animal research: raise standards to protect patients.

PMID- 18818631
TI  - Energy: efficiency gains alone won't reduce emissions.

PMID- 18818633
TI  - Energy: time to consider heavy-metal nuclear coolants?

PMID- 18818632
TI  - Big data: open-source format needed to aid wiki collaboration.

PMID- 18818634
TI  - Big data: teaching must evolve to keep up with advances.

PMID- 18818635
TI  - A cat's cradle for policy.

PMID- 18818641
TI  - Meetings that changed the world: Bellagio 1969: The green revolution.

PMID- 18818642
TI  - Structural biology: A moving story of receptors.

PMID- 18818643
TI  - Solid-state physics: New order for magnetism.

PMID- 18818644
TI  - Hearing: Route to authentic hair cells.

PMID- 18818645
TI  - Astrophysics: How fast can you blink?

PMID- 18818646
TI  - Neuroscience: An ageing view of myelin repair.

PMID- 18818647
TI  - Cancer: Entangled pathways.

PMID- 18818648
TI  - Microbiology: metagenomics.

PMID- 18818649
TI  - Frequency-modulated nuclear localization bursts coordinate gene regulation.
AB  - In yeast, the transcription factor Crz1 is dephosphorylated and translocates into
      the nucleus in response to extracellular calcium. Here we show, using time-lapse
      microscopy, that Crz1 exhibits short bursts of nuclear localization (typically
      lasting 2 min) that occur stochastically in individual cells and propagate to the
      expression of downstream genes. Strikingly, calcium concentration controls the
      frequency, but not the duration, of localization bursts. Using an analytic model,
      we also show that this frequency modulation of bursts ensures proportional
      expression of multiple target genes across a wide dynamic range of expression
      levels, independent of promoter characteristics. We experimentally confirm this
      theory with natural and synthetic Crz1 target promoters. Another stress-response
      transcription factor, Msn2, exhibits similar, but largely uncorrelated,
      localization bursts under calcium stress suggesting that frequency-modulation
      regulation of localization bursts may be a general control strategy used by the
      cell to coordinate multi-gene responses to external signals.

PMID- 18818650
TI  - Crystal structure of opsin in its G-protein-interacting conformation.
AB  - Opsin, the ligand-free form of the G-protein-coupled receptor rhodopsin, at low
      pH adopts a conformationally distinct, active G-protein-binding state known as
      Ops*. A synthetic peptide derived from the main binding site of the
      heterotrimeric G protein-the carboxy terminus of the alpha-subunit (GalphaCT)
      stabilizes Ops*. Here we present the 3.2 A crystal structure of the bovine Ops*
      GalphaCT peptide complex. GalphaCT binds to a site in opsin that is opened by an
      outward tilt of transmembrane helix (TM) 6, a pairing of TM5 and TM6, and a
      restructured TM7-helix 8 kink. Contacts along the inner surface of TM5 and TM6
      induce an alpha-helical conformation in GalphaCT with a C-terminal reverse turn.
      Main-chain carbonyl groups in the reverse turn constitute the centre of a
      hydrogen-bonded network, which links the two receptor regions containing the
      conserved E(D)RY and NPxxY(x)(5,6)F motifs. On the basis of the Ops*-GalphaCT
      structure and known conformational changes in Galpha, we discuss signal transfer
      from the receptor to the G protein nucleotide-binding site.

PMID- 18818651
TI  - Very fast optical flaring from a possible new Galactic magnetar.
AB  - Highly luminous rapid flares are characteristic of processes around compact
      objects like white dwarfs, neutron stars and black holes. In the high-energy
      regime of X-rays and gamma-rays, outbursts with variabilities on timescales of
      seconds or less are routinely observed, for example in gamma-ray bursts or soft
      gamma-ray repeaters. At optical wavelengths, flaring activity on such timescales
      has not been observed, other than from the prompt phase of one exceptional gamma
      ray burst. This is mostly due to the fact that outbursts with strong, fast
      flaring are usually discovered in the high-energy regime; most optical follow-up
      observations of such transients use instruments with integration times exceeding
      tens of seconds, which are therefore unable to resolve fast variability. Here we
      show the observation of extremely bright and rapid optical flaring in the
      Galactic transient SWIFT J195509.6+261406. Our optical light curves are
      phenomenologically similar to high-energy light curves of soft gamma-ray
      repeaters and anomalous X-ray pulsars, which are thought to be neutron stars with
      extremely high magnetic fields (magnetars). This suggests that similar processes
      are in operation, but with strong emission in the optical, unlike in the case of
      other known magnetars.

PMID- 18818652
TI  - Flares from a candidate Galactic magnetar suggest a missing link to dim isolated
      neutron stars.
AB  - Magnetars are young neutron stars with very strong magnetic fields of the order
      of 10(14)-10(15) G. They are detected in our Galaxy either as soft gamma-ray
      repeaters or anomalous X-ray pulsars. Soft gamma-ray repeaters are a rare type of
      gamma-ray transient sources that are occasionally detected as bursters in the
      high-energy sky. No optical counterpart to the gamma-ray flares or the quiescent
      source has yet been identified. Here we report multi-wavelength observations of a
      puzzling source, SWIFT J195509+261406. We detected more than 40 flaring episodes
      in the optical band over a time span of three days, and a faint infrared flare 11
      days later, after which the source returned to quiescence. Our radio observations
      confirm a Galactic nature and establish a lower distance limit of approximately
      3.7 kpc. We suggest that SWIFT J195509+261406 could be an isolated magnetar whose
      bursting activity has been detected at optical wavelengths, and for which the
      long-term X-ray emission is short-lived. In this case, a new manifestation of
      magnetar activity has been recorded and we can consider SWIFT J195509+261406 to
      be a link between the 'persistent' soft gamma-ray repeaters/anomalous X-ray
      pulsars and dim isolated neutron stars.

PMID- 18818653
TI  - Reconstruction of non-classical cavity field states with snapshots of their
      decoherence.
AB  - The state of a microscopic system encodes its complete quantum description, from
      which the probabilities of all measurement outcomes are inferred. Being a
      statistical concept, the state cannot be obtained from a single system
      realization, but can instead be reconstructed from an ensemble of copies through
      measurements on different realizations. Reconstructing the state of a set of
      trapped particles shielded from their environment is an important step in the
      investigation of the quantum-classical boundary. Although trapped-atom state
      reconstructions have been achieved, it is challenging to perform similar
      experiments with trapped photons because cavities that can store light for very
      long times are required. Here we report the complete reconstruction and pictorial
      representation of a variety of radiation states trapped in a cavity in which
      several photons survive long enough to be repeatedly measured. Atoms crossing the
      cavity one by one are used to extract information about the field. We obtain
      images of coherent states, Fock states with a definite photon number and
      'Schrodinger cat' states (superpositions of coherent states with different
      phases). These states are equivalently represented by their density matrices or
      Wigner functions. Quasi-classical coherent states have a Gaussian-shaped Wigner
      function, whereas the Wigner functions of Fock and Schrodinger cat states show
      oscillations and negativities revealing quantum interferences. Cavity damping
      induces decoherence that quickly washes out such oscillations. We observe this
      process and follow the evolution of decoherence by reconstructing snapshots of
      Schrodinger cat states at successive times. Our reconstruction procedure is a
      useful tool for further decoherence and quantum feedback studies of fields
      trapped in one or two cavities.

PMID- 18818654
TI  - Magnetization vector manipulation by electric fields.
AB  - Conventional semiconductor devices use electric fields to control conductivity, a
      scalar quantity, for information processing. In magnetic materials, the direction
      of magnetization, a vector quantity, is of fundamental importance. In magnetic
      data storage, magnetization is manipulated with a current-generated magnetic
      field (Oersted-Ampere field), and spin current is being studied for use in non
      volatile magnetic memories. To make control of magnetization fully compatible
      with semiconductor devices, it is highly desirable to control magnetization using
      electric fields. Conventionally, this is achieved by means of magnetostriction
      produced by mechanically generated strain through the use of piezoelectricity.
      Multiferroics have been widely studied in an alternative approach where
      ferroelectricity is combined with ferromagnetism. Magnetic-field control of
      electric polarization has been reported in these multiferroics using the
      magnetoelectric effect, but the inverse effect-direct electrical control of
      magnetization-has not so far been observed. Here we show that the manipulation of
      magnetization can be achieved solely by electric fields in a ferromagnetic
      semiconductor, (Ga,Mn)As. The magnetic anisotropy, which determines the
      magnetization direction, depends on the charge carrier (hole) concentration in
      (Ga,Mn)As. By applying an electric field using a metal-insulator-semiconductor
      structure, the hole concentration and, thereby, the magnetic anisotropy can be
      controlled, allowing manipulation of the magnetization direction.

PMID- 18818655
TI  - Observed and modelled stability of overflow across the Greenland-Scotland ridge.
AB  - Across the Greenland-Scotland ridge there is a continuous flow of cold dense
      water, termed 'overflow', from the Nordic seas to the Atlantic Ocean. This is a
      main contributor to the production of North Atlantic Deep Water that feeds the
      lower limb of the Atlantic meridional overturning circulation, which has been
      predicted to weaken as a consequence of climate change. The two main overflow
      branches pass the Denmark Strait and the Faroe Bank channel. Here we combine
      results from direct current measurements in the Faroe Bank channel for 1995-2005
      with an ensemble hindcast experiment for 1948-2005 using an ocean general
      circulation model. For the overlapping period we find a convincing agreement
      between model simulations and observations on monthly to interannual timescales.
      Both observations and model data show no significant trend in volume transport.
      In addition, for the whole 1948-2005 period, the model indicates no persistent
      trend in the Faroe Bank channel overflow or in the total overflow transport, in
      agreement with the few available historical observations. Deepening isopycnals in
      the Norwegian Sea have tended to decrease the pressure difference across the
      Greenland-Scotland ridge, but this has been compensated for by the effect of
      changes in sea level. In contrast with earlier studies, we therefore conclude
      that the Faroe Bank channel overflow, and also the total overflow, did not
      decrease consistently from 1950 to 2005, although the model does show a weakening
      total Atlantic meridional overturning circulation as a result of changes south of
      the Greenland-Scotland ridge.

PMID- 18818656
TI  - Intraseasonal interaction between the Madden-Julian Oscillation and the North
      Atlantic Oscillation.
AB  - Bridging the traditional gap between the spatio-temporal scales of weather and
      climate is a significant challenge facing the atmospheric community. In
      particular, progress in both medium-range and seasonal-to-interannual climate
      prediction relies on our understanding of recurrent weather patterns and the
      identification of specific causes responsible for their favoured occurrence,
      persistence or transition. Within this framework, I here present evidence that
      the main climate intra-seasonal oscillation in the tropics-the Madden-Julian
      Oscillation (MJO)-controls part of the distribution and sequences of the four
      daily weather regimes defined over the North Atlantic-European region in winter.
      North Atlantic Oscillation (NAO) regimes are the most affected, allowing for
      medium-range predictability of their phase far exceeding the limit of around one
      week that is usually quoted. The tropical-extratropical lagged relationship is
      asymmetrical. Positive NAO events mostly respond to a mid-latitude low-frequency
      wave train initiated by the MJO in the western-central tropical Pacific and
      propagating eastwards. Precursors for negative NAO events are found in the
      eastern tropical Pacific-western Atlantic, leading to changes along the North
      Atlantic storm track. Wave-breaking diagnostics tend to support the MJO
      preconditioning and the role of transient eddies in setting the phase of the NAO.
      I present a simple statistical model to quantitatively assess the potential
      predictability of the daily NAO index or the sign of the NAO regimes when they
      occur. Forecasts are successful in approximately 70 per cent of the cases based
      on the knowledge of the previous approximately 12-day MJO phase used as a
      predictor. This promising skill could be of importance considering the tight link
      between weather regimes and both mean conditions and the chances of extreme
      events occurring over Europe. These findings are useful for further stressing the
      need to better simulate and forecast the tropical coupled ocean-atmosphere
      dynamics, which is a source of medium-to-long range predictability and is the
      Achilles' heel of the current seamless prediction suites.

PMID- 18818657
TI  - FcRn-mediated antibody transport across epithelial cells revealed by electron
      tomography.
AB  - The neonatal Fc receptor (FcRn) transports maternal IgG across epithelial
      barriers, thereby providing the fetus or newborn with humoral immunity before its
      immune system is fully functional. In newborn rats, FcRn transfers IgG from milk
      to blood by apical-to-basolateral transcytosis across intestinal epithelial
      cells. The pH difference between the apical (pH 6.0-6.5) and basolateral (pH 7.4)
      sides of intestinal epithelial cells facilitates the efficient unidirectional
      transport of IgG, because FcRn binds IgG at pH 6.0-6.5 but not at pH 7 or more.
      As milk passes through the neonatal intestine, maternal IgG is removed by FcRn
      expressing cells in the proximal small intestine (duodenum and jejunum);
      remaining proteins are absorbed and degraded by FcRn-negative cells in the distal
      small intestine (ileum). Here we use electron tomography to make jejunal
      transcytosis visible directly in space and time, developing new labelling and
      detection methods to map individual nanogold-labelled Fc within transport
      vesicles and simultaneously to characterize these vesicles by immunolabelling.
      Combining electron tomography with a non-perturbing endocytic label allowed us to
      conclusively identify receptor-bound ligands, resolve interconnecting vesicles,
      determine whether a vesicle was microtubule-associated, and accurately trace FcRn
      mediated transport of IgG. Our results present a complex picture in which Fc
      moves through networks of entangled tubular and irregular vesicles, only some of
      which are microtubule-associated, as it migrates to the basolateral surface. New
      features of transcytosis are elucidated, including transport involving
      multivesicular body inner vesicles/tubules and exocytosis through clathrin-coated
      pits. Markers for early, late and recycling endosomes each labelled vesicles in
      different and overlapping morphological classes, revealing spatial complexity in
      endo-lysosomal trafficking.

PMID- 18818659
TI  - GABRG1 and GABRA2 as independent predictors for alcoholism in two populations.
AB  - The chromosome 4 cluster of GABA(A) receptor genes is predominantly expressed in
      the brain reward circuitry and this chromosomal region has been implicated in
      linkage scans for alcoholism. Variation in one chromosome 4 gene, GABRA2, has
      been robustly associated with alcohol use disorders (AUD) although no functional
      locus has been identified. As HapMap data reveal moderate long-distance linkage
      disequilibrium across GABRA2 and the adjacent gene, GABRG1, it is possible that
      the functional locus is in GABRG1. We genotyped 24 SNPs across GABRG1 and GABRA2
      in two population isolates: 547 Finnish Caucasian men (266 alcoholics) and 311
      community-derived Plains Indian men and women (181 alcoholics). In both the
      Plains Indians and the Caucasians: (1) the GABRG1 haplotype block(s) did not
      extend to GABRA2; (2) GABRG1 haplotypes and SNPs were significantly associated
      with AUD; (3) there was no association between GABRA2 haplotypes and AUD; (4)
      there were several common (>or=0.05) haplotypes that spanned GABRG1 and GABRA2
      (341 kb), three of which were present in both populations: one of these ancestral
      haplotypes was associated with AUD, the other two were more common in non
      alcoholics; this association was determined by GABRG1; (5) in the Finns, three
      less common (<0.05) extended haplotypes showed an association with AUD that was
      determined by GABRA2. Our results suggest that there are likely to be
      independent, complex contributions from both GABRG1 and GABRA2 to alcoholism
      vulnerability.

PMID- 18818660
TI  - Comment on "Does ferric gluconate lower epoetin requirements in hemodialysis
      patients with high ferritin levels?".

PMID- 18818662
TI  - Are global nephrology guidelines feasible?

PMID- 18818663
TI  - Platelet reference ranges for neonates, defined using data from over 47,000
      patients in a multihospital healthcare system.
AB  - OBJECTIVE: Identifying a platelet count as abnormal (thrombocytopenia or
      thrombocytosis) can facilitate recognizing various disease states. However, the
      published reference ranges for platelet counts in neonates may be imprecise, as
      they were generated from relatively small sample sizes and compiled before modern
      platelet enumeration methods. STUDY DESIGN: We derived new neonatal reference
      ranges for platelet counts and mean platelet volume (MPV) measurements using
      electronic data accumulated during a recent 6-year period from a multihospital
      healthcare system. RESULT: Platelet counts were obtained between the first and
      the 90th day after birth, from 47,291 neonates delivered at 22 to 42 weeks
      gestation. The first platelet counts obtained in the first 3 days of life,
      increased over the range of 22 to 42 weeks gestation. In those born < or =32
      weeks gestation, the lower reference range (5th percentile) was 104,200 microl(
      1), but it was 123,100 microl(-1) in late-preterm and -term neonates. Advancing
      postnatal age had a significant effect on platelet counts; during the first 9
      weeks, the counts fit a sinusoidal pattern with two peaks; one at 2 to 3 weeks
      and a second at 6 to 7 weeks. The upper limit of expected counts (95th
      percentile) during these peaks were as high as 750,000 microl(-1). CONCLUSION:
      The figures herein describe reference ranges for platelet counts and MPV
      determinations of neonates at various gestational ages during their first 90
      days. Expected values differ substantially from the 150,000 microl(-1) to 450,000
      microl(-1) range previously used to define neonatal thrombocytopenia and
      thrombocytosis. The new definitions will render the diagnoses of neonatal
      thrombocytopenia and thrombocytosis less commonly than when the old definitions
      were used, because the new ranges are wider than 150,000 microl(-1) to 450,000
      microl(-1).

PMID- 18818664
TI  - Feeding abilities in neonates with congenital heart disease: a retrospective
      study.
AB  - OBJECTIVE: An important area concerning morbidity among infants with congenital
      heart defects (CHD) is related to feeding problems. Our objectives were to
      characterize the evolution of feeding milestones related to transition to per
      oral feeding among infants with CHD, and to identify associated variables
      impacting the feeding abilities. Specifically, we differentiated the feeding
      characteristics in neonates with acyanotic vs cyanotic CHD. STUDY DESIGN: Feeding
      progress was tracked during the first hospitalization in a retrospective chart
      review study involving 76 infants (29 acyanotic, 47 cyanotic CHD). The ages at
      which the following milestones attained were recorded: first feeds, maximum
      gavage feeds, first nipple feeds and maximum nipple feeds, in addition to the
      length of hospital stay. Effects of perinatal factors, duration of respiratory
      support, vasopressor and narcotic use and use of cardiopulmonary bypass on the
      feeding milestones were also evaluated. ANOVA, t-test, and stepwise linear
      regression analysis were applied as appropriate. Data stated as mean+/-s.e.m., or
      %; P<0.05 was considered significant. RESULT: Prenatal and birth characteristics
      were similar (P=NS) between the neonates with acyanotic and cyanotic CHD.
      Cyanotic CHD required three times prolonged use of ventilation, narcotics and
      vasopressor use (all P<0.05, compared to the acyanotic group). In the acyanotic
      group, prolonged respiratory support correlated linearly with time to attain
      maximal gavage feeds and nippling (both, R2=0.8). In the cyanotic group, delayed
      initiation of gavage feeds and prolonged respiratory support both correlated
      linearly with time to attain maximal gavage feeds and nippling (both, R2=0.8).
      Age at first gavage feed correlated with maximum gavage feeds among neonates with
      cyanotic CHD, and first nipple feed correlated with maximum nipple feeds among
      all groups (P<0.01). Use of cardiopulmonary bypass in cyanotic CHD delayed the
      feeding milestones and prolonged the length of stay (both, P<0.05 vs non-bypass
      group); similar findings were not seen in the acyanotic group. CONCLUSION: In
      contrast to neonates with acyanotic CHD, cyanotic CHD group had significant
      delays with (a) feeding readiness, (b) successful gastric feeding, (c) oromotor
      readiness and (d) successful oromotor skills. Co-morbid factors that may directly
      influence the delay in feeding milestones include the (a) duration of respiratory
      support and (b) use of cardiopulmonary bypass. Delays in achieving maximum gavage
      and maximum nippling may suggest foregut dysmotility and oropharyngeal dysphagia.

PMID- 18818665
TI  - Chaos, vulnerability and control: parental beliefs about neonatal clinical
      trials.
AB  - OBJECTIVE: This study examined parental beliefs about participating in clinical
      trials involving greater than minimal risk to their neonate, and explored their
      views of their experiences. STUDY DESIGN: In this qualitative descriptive study,
      parents in the neonatal intensive care unit (NICU) who had been approached for
      permission for their neonates to be enrolled in research were asked to describe
      their decisions about their consent for or disagreement to their neonate's
      research participation. A total of 27 parents from three different hospital NICUs
      in the Mid-Atlantic region of the United States participated. Transcribed
      interviews were analyzed using qualitative content analysis. RESULTS: Participant
      decisions developed through a dynamic process of meaning-making based on their
      beliefs about themselves and their neonates. The processes involved making sense
      of the chaos that they perceived in the environment and their own vulnerability,
      through taking control of their situation.

PMID- 18818666
TI  - Structural insights into microneme protein assembly reveal a new mode of EGF
      domain recognition.
AB  - The obligate intracellular parasite Toxoplasma gondii, a member of the phylum
      Apicomplexa that includes Plasmodium spp., is one of the most widespread
      parasites and the causative agent of toxoplasmosis. Adhesive complexes composed
      of microneme proteins (MICs) are secreted onto the parasite surface from
      intracellular stores and fulfil crucial roles in host-cell recognition,
      attachment and penetration. Here, we report the high-resolution solution
      structure of a complex between two crucial MICs, TgMIC6 and TgMIC1. Furthermore,
      we identify two analogous interaction sites within separate epidermal growth
      factor-like (EGF) domains of TgMIC6-EGF2 and EGF3-and confirm that both
      interactions are functional for the recognition of host cell receptor in the
      parasite, using immunofluorescence and invasion assays. The nature of this new
      mode of recognition of the EGF domain and its abundance in apicomplexan surface
      proteins suggest a more generalized means of constructing functional assemblies
      by using EGF domains with highly specific receptor-binding properties.

PMID- 18818667
TI  - Selective role of calcineurin in haematopoiesis and lymphopoiesis.
AB  - The calcineurin/NFAT (nuclear factor of activated T-cells) signalling pathway is
      essential for many aspects of vertebrate development and is the target of the
      widely used immunosuppressive drugs FK506 and cyclosporine A. The basis for the
      therapeutic specificity of these drugs has remained unclear, as calcineurin is
      expressed ubiquitously. By inactivating calcineurin during haematopoietic
      development, we found that although this signalling pathway has an important, non
      redundant role in the regulation of lymphocyte developmental checkpoints, it is
      not essential for the development of blood myeloid lineages. These studies have
      shown that the specificity of calcineurin inhibitors arises from the selective
      use of calcineurin at distinct developmental stages. The requirement for
      calcineurin/NFAT in the development of the adaptive but not of the innate immune
      system is consistent with the idea that the evolutionary appearance of this
      pathway was involved in the emergence of vertebrates.

PMID- 18818668
TI  - Systemic delivery of IL-10 by an AAV vector prevents vascular remodeling and end
      organ damage in stroke-prone spontaneously hypertensive rat.
AB  - Interleukin-10 (IL-10) ameliorates various T-helper type 1 cell-mediated chronic
      inflammatory diseases. Although the therapeutic benefits of IL-10 include
      antiatherosclerotic effects, pathophysiological effects of IL-10 on vascular
      remodeling in hypertension have not yet been elucidated. These studies were
      designed to determine whether sustained IL-10 expression, mediated by an adeno
      associated virus (AAV) vector, prevents vascular remodeling and target-organ
      damage in the stroke-prone spontaneously hypertensive rat (SHR-SP)-an animal
      model of malignant hypertension. A single intramuscular injection of an AAV1
      vector encoding rat IL-10 introduced long-term IL-10 expression. These IL-10
      transduced rats had decreased stroke episodes and proteinuria, resulting in
      improved survival. Histological examination revealed a reduced level of
      deleterious vascular remodeling of resistance vessels in the brain and kidney of
      these rats. Immunohistochemical analysis indicated that IL-10 inhibited the
      enhanced renal transforming growth factor-beta expression and perivascular
      infiltration of monocytes/macrophages and nuclear factor-kappaB-positive cells
      normally observed in the SHR-SP. Four weeks after IL-10 vector injection,
      systolic blood pressure significantly decreased and this effect persisted for
      several months. Overall, AAV vector-mediated systemic IL-10 expression prevented
      vascular remodeling and inflammatory lesions of target organs in the SHR-SP. This
      approach provides significant insights into the prevention strategy of disease
      onset with unknown genetic predisposition or intractable polygenic disorders.

PMID- 18818669
TI  - The pros and cons of immunomodulatory IL-10 gene therapy with recombinant AAV in
      a Cftr-/- -dependent allergy mouse model.
AB  - Cystic fibrosis (CF) patients have decreased levels of lung epithelial
      interleukin (IL)-10 and increased levels of proinflammatory cytokines (tumor
      necrosis factor-alpha, IL-4, IL-8 and IL-6). This has also been documented in
      Cftr (cystic fibrosis transmembrane conductance regulator)-deficient mice (Cftr
      489X(-/-), FABP-hCFTR(+/+)). Our laboratory has recently characterized a peculiar
      hyper-IgE phenotype in these mice, in response to Aspergillus fumigatus crude
      protein extract (Af-cpe). Thus, we hypothesized that sustained systemic
      circulating IL-10 levels achieved through skeletal muscle transduction with
      recombinant adeno-associated vectors expressing IL-10 (rAAV1-IL-10) would serve
      to downregulate Th1 and Th2 cytokine production. This in turn would dampen the
      allergic response in the Cftr(-/-)-dependent mouse model of allergic
      bronchopulmonary aspergillosis. After Af-cpe sensitization and airway challenge,
      mice treated with rAAV1-IL-10 had markedly lower IgE levels when compared to the
      control-treated rAAV1-GFP group. This was accompanied by a significant reduction
      in the levels of IL-5, IL-4 and IL-13 in the lung compartment. The lower lung
      cytokine profiles resulted in a near absence of eosinophil recruitment in the
      lung and a lower inflammatory response in the lung tissue of mice receiving rAAV1
      IL-10. Unfortunately, sustained secretion of IL-10 from transduced muscle did
      lead to thrombocytopenia and splenomegaly in mice injected with rAAV1-IL-10.
      These results highlight that while IL-10 gene therapy is very effective for
      treating allergic responses caution must be taken with the prolonged secretion of
      IL-10.

PMID- 18818670
TI  - Controlled propagation of replication-competent Sindbis viral vector using
      suicide gene strategy.
AB  - A major concern of using viral gene therapy is the potential for uncontrolled
      vector propagation and infection that might result in serious deleterious
      effects. To enhance the safety, several viral vectors, including vectors based on
      Sindbis virus, were engineered to lose their capability to replicate and spread
      after transduction of target cells. Such designs, however, could dramatically
      reduce the therapeutic potency of the viral vectors, resulting in the need for
      multiple dosages to achieve treatment goals. Earlier, we showed that a
      replication-defective (RD) Sindbis vector achieved specific tumor targeting
      without any adverse effects in vivo. Here, we present a replication-competent
      Sindbis viral vector that has an hsvtk suicide gene incorporated into ns3, an
      indispensable non-structural gene for viral survival. The capability of viral
      propagation significantly increases tumor-specific infection and enhances growth
      suppression of tumor compared with the conventional RD vectors. Furthermore, in
      the presence of the prodrug ganciclovir, the hsvtk suicide gene serves as a
      safety mechanism to prevent uncontrolled vector propagation. In addition to
      suppressing vector propagation, toxic metabolites, generated by prodrug
      activation, could spread to neighboring uninfected tumor cells to further enhance
      tumor killing.

PMID- 18818671
TI  - Mechanisms of distribution of mouse beta-galactosidase in the adult GM1
      gangliosidosis brain.
AB  - GM1-gangliosidosis is a lysosomal storage disease (LSD) caused by an autosomal
      recessive deficiency of lysosomal acid beta-galactosidase (betagal). This leads
      to accumulation of GM1-ganglioside and its asialo derivative GA1 in the central
      nervous system (CNS), and progressive neurodegeneration. Therapeutic AAV-mediated
      gene delivery to the brain for LSDs has proven very successful in several animal
      models. GM1-gangliosidosis is also a prime candidate for AAV-mediated gene
      therapy in the CNS. As global neuropathology characterizes the most severe forms
      of this disease, therapeutic interventions need to achieve distribution of
      betagal throughout the entire CNS. Therefore, careful consideration of routes of
      administration and target structures from where metabolically active enzyme can
      be produced, released and distributed throughout the CNS, is necessary. The goal
      of this study was to investigate the pattern and mechanism of distribution of
      betagal in the adult GM1-gangliosidosis mouse brain upon hippocampal injection of
      an AAV vector-encoding betagal. We found evidence that three different mechanisms
      contribute to its distribution in the brain: (1) diffusion; (2) axonal transport
      within neurons from the site of production; (3) CSF flow in the perivascular
      space of Virchow-Robin. In addition, we found evidence of axonal transport of
      vector-encoded mRNA.

PMID- 18818672
TI  - A new paradigm for the role of aging in the development of skin cancer.

PMID- 18818673
TI  - Complexity of VEGF responses in skin carcinogenesis revealed through ex vivo
      assays based on a VEGF-A null mouse keratinocyte cell line.
AB  - Vascular endothelial growth factor (VEGF-A) is a critical player in cutaneous
      angiogenesis. However, the relative contribution of VEGF-A from different sources
      including epithelial and mesenchymal cells has not been fully characterized
      during skin repair and tumorigenesis. Moreover, the actual involvement of other
      vascular-specific acting molecules has remained elusive in part due to the
      masking and/or overlapping effects of VEGF-A. To shed light on these
      uncertainties we generated and characterized a clonal VEGF-null mouse
      keratinocyte cell line, through in vitro adenoviral gene transfer of Cre
      recombinase to VEGF-LoxP primary keratinocytes followed by repeated cell
      passaging under controlled conditions and cloning. In vitro and in vivo assays
      demonstrated that VEGF-null keratinocytes were nontumorigenic and expressed
      normal differentiation markers after calcium switch. Hras-induced tumorigenesis
      of immortalized VEGF-null keratinocytes upon subcutaneous injection was markedly
      reduced but not fully suppressed. However, the metastatic ability of Hras
      transformed VEGF-null keratinocytes was abolished. These ex vivo approaches
      suggest the existence of VEGF-dependent and independent angiogenic stimuli in
      skin carcinogenesis. The VEGF-null mouse keratinocyte cell line arises as an
      important tool to assess the actual contribution of keratinocyte-derived VEGF
      with respect to other angiogenic factors in skin homeostasis and malignancy.

PMID- 18818674
TI  - Enzyme-independent NO stores in human skin: quantification and influence of UV
      radiation.
AB  - Nitric oxide (NO) has many functions in the skin, including the mediation of
      inflammation and antimicrobial defense, wound healing, regulation of keratinocyte
      homeostasis, and regulation of apoptosis following UV radiation. NO is
      synthesized by a family of NO synthase enzymes, but its rapid release following
      UV exposure suggests the existence of preformed stores. NO can be converted into
      nitrite or nitrosothiols that are stable until cleaved by UV to release NO. Using
      dermal microdialysis, suction blister epidermal samples, and sweat collection, we
      demonstrated cutaneous concentrations of total NO-related products of 12+/-5.97
      microM, 0.03+/-0.03 micromol mg(-1) epidermal protein, and 22+/-9.34 microM,
      respectively. The predominant oxyanion was nitrate (60-75%) followed by nitrite.
      S-Nitrosothiols were barely detectable. Serum total NO-related products
      correlated directly with those of the upper dermis and sweat (R(2)=0.62 and 0.3,
      respectively). UVA irradiation (10 mW cm(-2)) increased the yield of NO-related
      products by microdialysis, peaking after 30 minutes. Dialysis with noradrenaline
      abrogated this rise. Both the skin and the dermal vasculature contain
      biologically significant stores of NO, particularly nitrite, which can be
      directly mobilized by UVA irradiation. The level of circulating NO-related
      products probably determines skin-bound stores.

PMID- 18818675
TI  - Circumscribed palmo-plantar hypokeratosis: a disease with two subtypes.

PMID- 18818676
TI  - Clinical severity correlates with impaired barrier in filaggrin-related eczema.
AB  - Mutations in the gene-encoding filaggrin (FLG), a key molecule involved in skin
      barrier function, have been shown to be a major predisposing factor for atopic
      dermatitis (AD; eczema). To elucidate the pathomechanisms underlying filaggrin
      related AD, we investigated stratum corneum (SC) hydration and transepidermal
      water loss (TEWL) as parameters of barrier function in AD patients harboring FLG
      mutations compared to AD patients without any FLG mutation. In filaggrin-related
      AD, SC hydration was both significantly reduced (P<0.01-0.05) and thicker (P<0.01
      0.05) than that in healthy controls. TEWL was demonstrably increased in non
      filaggrin AD compared to healthy controls (P<0.01-0.05). The objective score of
      atopic dermatitis (OSCORAD), a disease clinical severity index, significantly
      correlated with TEWL (r=0.81, P<0.005), SC hydration (r=-0.65, P<0.05), and SC
      thickness (r=0.59, P<0.05) in filaggrin-related AD. On the contrary, there was no
      correlation between these parameters and the OSCORAD in non-filaggrin AD.
      Furthermore, a significant correlation was obtained between the OSCORAD and
      specific IgE for house dust (r=0.66, P<0.05), mite allergen (r=0.53, P<0.05), and
      cat dander (r=0.64, P<0.05) in filaggrin-related AD, but not in non-filaggrin AD.
      All these data suggest that experimentally demonstrable skin barrier defects due
      to FLG mutations may play a crucial role in the pathogenesis of AD.

PMID- 18818677
TI  - Calmodulin-like protein upregulates myosin-10 in human keratinocytes and is
      regulated during epidermal wound healing in vivo.
AB  - Epidermal wound healing is required for normal skin barrier function. Cell
      motility is a key factor in the ability of keratinocytes to heal epithelial
      damage. Calmodulin-like protein (CLP) is an epithelial-specific Ca(2+)-binding
      protein that is regulated during terminal keratinocyte differentiation. CLP is a
      specific light chain of unconventional myosin-10 (Myo10) and its expression
      increases filopodial length, filopodial number, and Myo10-dependent cell motility
      in vitro. However, the effects of CLP expression on keratinocyte motility are
      unknown. Here we used cultured human keratinocytes to study the role of CLP in
      regulating Myo10 and the effects of Myo10 and CLP on cell migration. CLP and
      Myo10 expression were correlated in vitro and required for keratinocyte motility
      in wound-healing assays. We examined the localization of CLP in wounded skin by
      immunohistochemistry and found an upregulation and peripheral localization of CLP
      in the basal and suprabasal cells adjacent to and immediately over the wound bed
      in vivo. The results suggest that increased CLP expression and CLP-mediated Myo10
      function are important for skin differentiation and wound reepithelialization.

PMID- 18818678
TI  - Absence of germline epimutation of the CDKN2A gene in familial melanoma.

PMID- 18818679
TI  - Effect of atorvastatin on inflammation and outcome in patients with type 2
      diabetes mellitus on hemodialysis.
AB  - Statins have multiple effects, including anti-inflammatory actions, lowering C
      reactive protein levels, and reducing coronary events. We performed a post hoc
      analysis of the randomized placebo-controlled 4D Study that had evaluated the
      efficacy and safety of atorvastatin in 1255 patients with type 2 diabetes
      mellitus who were on maintenance hemodialysis. Here we determined the
      relationship between atorvastatin treatment, C-reactive protein, and the outcome
      of patients who had pre-specified and adjudicated endpoints of all-cause
      mortality, composite vascular endpoint, myocardial infarction, sudden death, and
      stroke. Atorvastatin had no significant effect on the risk of composite vascular
      endpoint or death relative to placebo in any quartile of baseline C-reactive
      protein. These baseline levels were not significantly different between the
      treated and placebo group and remained stable at 6 months on atorvastatin but
      significantly increased in those patients on placebo. All of the patients with
      baseline C-reactive protein in the fourth quartile had a significantly increased
      risk of deaths and in composite vascular endpoint compared to patients in the
      first quartile. The mean value of two consecutive C-reactive protein measurements
      was associated with significant increases in the risk of sudden death, stroke,
      all-cause mortality and composite vascular endpoint. Our results show that C
      reactive protein was highly predictive of outcome, but atorvastatin treatment was
      not associated with reduced relative risks in the composite vascular endpoint or
      mortality in patients on hemodialysis with or without inflammation.

PMID- 18818680
TI  - Erythropoiesis-stimulating agent treatment with full anemia correction: a new
      perspective.
AB  - Erythropoiesis stimulating agent (ESA) treatment has been a major advance in the
      care of patients with kidney disease, resulting in reduced symptoms and blood
      transfusions, and improved quality of life. Recent studies, however, have
      indicated that attempts to treat to near normal Hgb targets may result in
      increased risk for death or cardiovascular events. This had led to an appropriate
      increase in caution, and avoidance of Hgb targets greater than 13 g/dl. There is,
      however, a great lack of understanding of the mechanisms of harm with more
      intensive ESA treatment. One avenue for investigation in medicine is analysis of
      outlier experience. In this article we will consider the experience of a group of
      dialysis units in Berlin, Germany, that have achieved outstanding patient
      outcomes despite targeting normal Hgb levels with ESA treatment. The purpose is
      to explore ancillary treatment processes that could mitigate any harmful effects
      of ESA therapy. We do not seek to propose that treatment with ESAs to higher Hgb
      targets is safe, but rather to use this outlier experience to gain knowledge and
      to generate hypotheses to be tested in future studies.

PMID- 18818681
TI  - Regulation of oxygen utilization by angiotensin II in chronic kidney disease.
AB  - Angiotensin II blockade delays progression of chronic kidney disease by modifying
      intrarenal hemodynamics, but the effects on metabolic adaptations are unknown.
      Using the remnant kidney model of chronic kidney disease in rats, we measured the
      effects of combined angiotensin II blockade with captopril and losartan on renal
      oxygen consumption (QO(2)) and factors influencing QO(2). Remnant kidneys had
      proteinuria and reductions in the glomerular filtration rate (GFR), renal blood
      flow (RBF) and nitric oxide synthase-1 protein expression while QO(2), factored
      by sodium reabsorption (QO(2)/TNa), was markedly increased. Combined blockade
      treatment normalized these parameters while increasing sodium reabsorption but,
      since QO(2) was unchanged, QO(2)/TNa also normalized. Triple antihypertensive
      therapy, to control blood pressure, and treatment with lysine, to increase GFR
      and RBF, did not normalize QO(2)/TNa, suggesting a specific effect of angiotensin
      II in elevating QO(2)/TNa. Inhibition of nitric oxide synthase increased QO(2) in
      the kidney of sham-operated rats but not in the remnant kidney of untreated rats.
      Our study shows that combined captopril and losartan treatment normalized
      QO(2)/TNa and functional nitric oxide activity in the remnant kidney independent
      of blood pressure and GFR effects, suggesting that other mechanisms in addition
      to hemodynamics underlie the benefits of angiotensin II blockade.

PMID- 18818682
TI  - Inhibition of JAK2 protects renal endothelial and epithelial cells from oxidative
      stress and cyclosporin A toxicity.
AB  - Cyclosporin A is an immunosuppressant drug widely used in solid organ
      transplantation, but it has nephrotoxic properties that promote oxidative stress.
      The JAK2/STAT pathway has been implicated in both cell protection and cell
      injury; therefore, we determined a role of JAK2 in oxidative stress-mediated
      renal cell injury using pathophysiologically relevant oxidative challenges. The
      AG490 JAK2 inhibitor and overexpression of a dominant negative JAK2 protein
      protected endothelial and renal epithelial cells in culture against peroxide,
      superoxide anion and cyclosporin A induced cell death while reducing
      intracellular oxidation in cells challenged with peroxide and cyclosporin A. The
      decrease in Bcl2 expression and caspase 3 activation, induced by oxidative
      stress, was prevented by AG490. In mouse models of ischemia/reperfusion and
      cyclosporin A nephrotoxicity, AG490 decreased peritubular capillary and tubular
      cell injury. Our study shows that JAK2 inhibition is a promising renoprotective
      strategy defending endothelial and tubular cells from cyclosporin A- and
      oxidative stress-induced death.

PMID- 18818684
TI  - Location of acute coronary artery thromboses in patients with and without chronic
      kidney disease.
AB  - Patients with chronic kidney disease have high rates of myocardial infarction and
      death following an initial attack. Proximal location of coronary atherosclerotic
      lesions has been linked to the risk of acute myocardial infarction and to
      infarction-associated mortality. To examine if the spatial distribution of
      lesions differs in patients with and without chronic kidney disease, we used
      quantitative coronary angiography to measure this in patients with acute coronary
      thromboses who were having angiography following acute myocardial infarction.
      Multivariable linear regression was used to adjust for differences in baseline
      characteristics. Among 82 patients with stage 3 or higher chronic kidney disease,
      55.6% of lesions were located within 30 mm and 87.7% were within 50 mm of the
      coronary ostia. This compared to 34.7 and 71.8%, respectively, among 299 patients
      without significant kidney disease. Chronic kidney disease was independently and
      significantly associated with a 7.0 mm decrease in the distance from the coronary
      ostia to the problem lesion. Our study suggests that a causal link between a more
      proximal culprit lesion location in patients with chronic kidney disease and
      their high mortality rates after myocardial infarct is possible and may have
      important implications for interventions to prevent infarction.

PMID- 18818683
TI  - Characterization of large rearrangements in autosomal dominant polycystic kidney
      disease and the PKD1/TSC2 contiguous gene syndrome.
AB  - Large DNA rearrangements account for about 8% of disease mutations and are more
      common in duplicated genomic regions, where they are difficult to detect.
      Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in
      either PKD1 or PKD2. PKD1 is located in an intrachromosomally duplicated region.
      A tuberous sclerosis gene, TSC2, lies immediately adjacent to PKD1 and large
      deletions can result in the PKD1/TSC2 contiguous gene deletion syndrome. To
      rapidly identify large rearrangements, a multiplex ligation-dependent probe
      amplification assay was developed employing base-pair differences between PKD1
      and the six pseudogenes to generate PKD1-specific probes. All changes in a set of
      25 previously defined deletions in PKD1, PKD2 and PKD1/TSC2 were detected by this
      assay and we also found 14 new mutations at these loci. About 4% of the ADPKD
      patients in the CRISP study were found to have gross rearrangements, and these
      accounted for about a third of base-pair mutation negative families. Sensitivity
      of the assay showed that about 40% of PKD1/TSC contiguous gene deletion syndrome
      families contained mosaic cases. Characterization of a family found to be mosaic
      for a PKD1 deletion is discussed here to illustrate family risk and donor
      selection considerations. Our assay improves detection levels and the reliability
      of molecular testing of patients with ADPKD.

PMID- 18818685
TI  - Increased E-cadherin expression in the ligated kidney following unilateral
      ureteric obstruction.
AB  - E-cadherin expression in the kidney is used as a surrogate marker of epithelial
      mesenchymal transition for the testing of various antifibrotic strategies. Here
      we reexamined E-cadherin expression in the kidneys of rats with unilateral
      ureteric obstruction, which was previously reported to decrease in parallel with
      the development of tubulointerstitial disease in this widely used experimental
      model of renal fibrosis and epithelial mesenchymal transition. E-cadherin mRNA
      expression was consistently increased both acutely (hours) and chronically (days)
      in the ligated kidney compared to the cognate non-ligated kidney. Increased E
      cadherin protein levels were also found in the ligated kidney particularly in
      dilated tubular segments. Simulation of early pressure changes in the ligated
      kidney by mechanical stretch of human renal epithelial cells in culture did not
      alter E-cadherin expression. Porcine LLCPK-1 cells subjected to hypotonic
      stretch, however, did have increased E-cadherin mRNA and protein levels,
      responses that were not prevented by transforming growth factor-beta, a cytokine
      that promotes epithelial mesenchymal transition. Our findings question the
      utility of E-cadherin as a marker of epithelial mesenchymal transition in this
      model of renal fibrosis.

PMID- 18818686
TI  - Hemodynamic wall shear stress profiles influence the magnitude and pattern of
      stenosis in a pig AV fistula.
AB  - Venous stenosis is a significant problem in arteriovenous fistulae, likely due to
      anatomical configuration and wall shear stress profiles. To identify linkages
      between wall shear stress and the magnitude and pattern of vascular stenosis, we
      produced curved and straight fistulae in a pig model. A complete wall stress
      profile was calculated for the curved configuration and correlated with luminal
      stenosis. Computer modeling techniques were then used to derive a wall shear
      stress profile for the straight arteriovenous fistula. Differences in the wall
      shear stress profile of the curved and straight fistula were then related to
      histological findings. There was a marked inverse correlation between the
      magnitude of wall shear stress within different regions of the curved
      arteriovenous fistula and luminal stenosis in these same regions. There were also
      significantly greater differences in wall shear stress between the outer and
      inner walls of the straight as compared to curved arteriovenous fistula, which
      translated into a more eccentric histological pattern of intima-media thickening.
      Our results suggest a clear linkage between anatomical configuration, wall shear
      stress profiles, and the pattern of luminal stenosis and intima-media thickening
      in a pig model of arteriovenous fistula stenosis. These results suggest that
      fistula failure could be reduced by using computer modeling prior to surgical
      placement to alter the anatomical and, consequently, the wall shear stress
      profiles in an arteriovenous fistula.

PMID- 18818687
TI  - Epigenetics and the control of epithelial sodium channel expression in collecting
      duct.
AB  - In eukaryotic nuclei, genomic DNA is compacted with histone and nonhistone
      proteins into a dynamic polymer termed chromatin. Reorganization of chromatin
      structure through histone modifications, the action of chromatin factors, or DNA
      methylation, can profoundly change gene expression. These epigenetic
      modifications allow heritable and potentially reversible changes in gene
      functioning to occur without altering the DNA sequence, thus extending the
      information potential of the genetic code. This review provides an introduction
      to epigenetic concepts for renal investigators and an overview of our work
      detailing an epigenetic pathway for aldosterone signaling and the control of
      epithelial Na(+) channel-alpha (ENaCalpha) subunit gene expression in the
      collecting duct. This new pathway involves a nuclear repressor complex,
      consisting of histone H3 Lys-79 methyltransferase disruptor of telomeric
      silencing-1a (Dot1a), ALL1 fused gene from chromosome 9 (Af9), a sequence
      specific DNA-binding protein that binds the ENaCalpha promoter, and potentially
      other nuclear proteins. This complex regulates targeted histone H3 Lys-79
      methylation of chromatin associated with the ENaCalpha promoter, thereby
      suppressing its transcriptional activity. Aldosterone disrupts the Dot1a-Af9
      interaction by serum- and glucocorticoid-induced kinase-1 phosphorylation of Af9,
      and inhibits Dot1a and Af9 expression, resulting in histone H3 Lys-79
      hypomethylation at specific subregions, and derepression of the ENaCalpha
      promoter. The Dot1a-Af9 pathway may also be involved in the control of genes
      implicated in renal fibrosis and hypertension.

PMID- 18818688
TI  - Sodium thiosulfate prevents vascular calcifications in uremic rats.
AB  - Accelerated vascular calcification is a severe complication of chronic kidney
      disease contributing to high morbidity and mortality in patients undergoing renal
      replacement therapy. Sodium thiosulfate is increasingly used for the treatment of
      soft tissue calcifications in calciphylaxis. Therefore, we determined whether it
      also prevents development of vascular calcifications in chronic kidney disease.
      We found that uremic rats treated by thiosulfate had no histological evidence of
      calcification in the aortic wall whereas almost three-fourths of untreated uremic
      rats showed aortic calcification. Urinary calcium excretion was elevated and the
      calcium content of aortic, heart, and renal tissue was significantly reduced in
      the thiosulfate-treated compared to non-treated animals. Sodium thiosulfate
      treatment transiently lowered plasma ionized calcium and induced metabolic
      acidosis. It also lowered bone strength in the treated animals compared to their
      normal controls. Hence, sodium thiosulfate prevented vascular calcifications in
      uremic rats, likely by enhancing acid- and/or chelation-induced urinary calcium
      loss. The negative impact on rat bone integrity necessitates a careful risk
      benefit analysis before sodium thiosulfate can be used in individual human
      patients.

PMID- 18818689
TI  - Radiation oncology health technology assessment: the best is the enemy of the
      good.

PMID- 18818690
TI  - Irf4 is a positional and functional candidate gene for the control of serum IgM
      levels in the mouse.
AB  - Natural IgM are involved in numerous immunological functions but the genetic
      factors that control the homeostasis of its secretion and upholding remain
      unknown. Prompted by the finding that C57BL/6 mice had significantly lower serum
      levels of IgM when compared with BALB/c mice, we performed a genome-wide screen
      and found that the level of serum IgM was controlled by a QTL on chromosome 13
      reaching the highest level of association at marker D13Mit266 (LOD score=3.54).
      This locus was named IgMSC1 and covered a region encompassing the interferon
      regulatory factor 4 gene (Irf4). The number of splenic mature B cells in C57BL/6
      did not differ from BALB/c mice but we found that low serum levels of IgM in
      C57BL/6 mice correlated with lower frequency of IgM-secreting cells in the spleen
      and in the peritoneal cavity. These results suggested that C57BL/6 mice have
      lower efficiency in late B-cell maturation, a process that is highly impaired in
      Irf4 knockout mice. In fact, we also found reduced Irf4 gene expression in B
      cells of C57BL/6 mice. Thus, we propose Irf4 as a candidate for the IgMSC1 locus,
      which controls IgM homeostatic levels at the level of B-cell terminal
      differentiation.

PMID- 18818691
TI  - IKKalpha, a critical regulator of epidermal differentiation and a suppressor of
      skin cancer.
AB  - IkappaB kinase alpha (IKKalpha), one of the two catalytic subunits of the IKK
      complex involved in nuclear factor kappaB (NF-kappaB) activation, also functions
      as a molecular switch that controls epidermal differentiation. This unexpected
      function requires IKKalpha nuclear translocation but does not depend on its
      kinase activity, and is independent of NF-kappaB signalling. Ikkalpha(-/-) mice
      present with a hyperproliferative and undifferentiated epidermis characterized by
      complete absence of a granular layer and stratum corneum. Ikkalpha-deficient
      keratinocytes do not express terminal differentiation markers and continue to
      proliferate even when subjected to differentiation-inducing stimuli. This
      antiproliferative function of IKKalpha is also important for the suppression of
      squamous cell carcinogenesis. The exact mechanisms by which nuclear IKKalpha
      controls keratinocyte proliferation and differentiation remained mysterious for
      some time. Recent studies, however, have revealed that IKKalpha is a major
      cofactor in a TGFbeta-Smad2/3 signalling pathway that is Smad4 independent. This
      pathway controls cell cycle withdrawal during keratinocyte terminal
      differentiation. Although these are not the only functions of nuclear IKKalpha,
      this multifunctional protein is a key regulator of keratinocyte and epidermal
      differentiation and a critical suppressor of skin cancer.

PMID- 18818692
TI  - Cdk5 phosphorylates Cdh1 and modulates cyclin B1 stability in excitotoxicity.
AB  - Anaphase-promoting complex/cyclosome (APC/C), an E3 ubiquitin ligase that
      destabilizes cell cycle proteins, is activated by Cdh1 in post-mitotic neurons,
      where it regulates axonal growth, synaptic plasticity and survival. The APC/C
      Cdh1 substrate, cyclin B1, has been found to accumulate in degenerating brain
      areas in Alzheimer's disease and stroke. This highlights the importance of
      elucidating cyclin B1 regulation by APC/C-Cdh1 in neurons under stress conditions
      relevant to neurological disease. Here, we report that stimulation of N-methyl-D
      aspartate receptors (NMDARs) that occurs in neurodegenerative diseases promoted
      the accumulation of cyclin B1 in the nuclei of cortical neurons; this led the
      neurons to undergo apoptotic death. Moreover, we found that the Ser-40, Thr-121
      and Ser-163 triple phosphorylation of Cdh1 by the cyclin-dependent kinase-5
      (Cdk5)-p25 complex was necessary and sufficient for cyclin B1 stabilization and
      apoptotic death after NMDAR stimulation. These results reveal Cdh1 as a novel
      Cdk5 substrate that mediates cyclin B1 neuronal accumulation in excitotoxicity.

PMID- 18818693
TI  - DNA methylation in ES cells requires the lysine methyltransferase G9a but not its
      catalytic activity.
AB  - Histone H3K9 methylation is required for DNA methylation and silencing of
      repetitive elements in plants and filamentous fungi. In mammalian cells however,
      deletion of the H3K9 histone methyltransferases (HMTases) Suv39h1 and Suv39h2
      does not affect DNA methylation of the endogenous retrovirus murine leukaemia
      virus, indicating that H3K9 methylation is dispensable for DNA methylation of
      retrotransposons, or that a different HMTase is involved. We demonstrate that
      embryonic stem (ES) cells lacking the H3K9 HMTase G9a show a significant
      reduction in DNA methylation of retrotransposons, major satellite repeats and
      densely methylated CpG-rich promoters. Surprisingly, demethylated
      retrotransposons remain transcriptionally silent in G9a(-/-) cells, and show only
      a modest decrease in H3K9me2 and no decrease in H3K9me3 or HP1alpha binding,
      indicating that H3K9 methylation per se is not the relevant trigger for DNA
      methylation. Indeed, introduction of catalytically inactive G9a transgenes
      partially 'rescues' the DNA methylation defect observed in G9a(-/-) cells. Taken
      together, these observations reveal that H3K9me3 and HP1alpha recruitment to
      retrotransposons occurs independent of DNA methylation in ES cells and that G9a
      promotes DNA methylation independent of its HMTase activity.

PMID- 18818694
TI  - G9a/GLP complexes independently mediate H3K9 and DNA methylation to silence
      transcription.
AB  - Methylation of DNA and lysine 9 of histone H3 (H3K9) are well-conserved
      epigenetic marks for transcriptional silencing. Although H3K9 methylation directs
      DNA methylation in filamentous fungi and plants, this pathway has not been
      corroborated in mammals. G9a and GLP/Eu-HMTase1 are two-related mammalian lysine
      methyltransferases and a G9a/GLP heteromeric complex regulates H3K9 methylation
      of euchromatin. To elucidate the function of G9a/GLP-mediated H3K9 methylation in
      the regulation of DNA methylation and transcriptional silencing, we characterized
      ES cells expressing catalytically inactive mutants of G9a and/or GLP.
      Interestingly, in ES cells expressing a G9a-mutant/GLP complex that does not
      rescue global H3K9 methylation, G9a/GLP-target genes remain silent. The CpG sites
      of the promoter regions of these genes were hypermethylated in such mutant ES
      cells, but hypomethylated in G9a- or GLP-KO ES cells. Treatment with a DNA
      methyltransferase inhibitor reactivates these G9a/GLP-target genes in ES cells
      expressing catalytically inactive G9a/GLP proteins, but not the wild-type
      proteins. This is the first clear evidence that G9a/GLP suppresses transcription
      by independently inducing both H3K9 and DNA methylation.

PMID- 18818695
TI  - ABAP1 is a novel plant Armadillo BTB protein involved in DNA replication and
      transcription.
AB  - In multicellular organisms, organogenesis requires a tight control of the balance
      between cell division and cell differentiation. Distinct signalling pathways that
      connect both cellular processes with developmental cues might have evolved to
      suit different developmental plans. Here, we identified and characterized a novel
      protein that interacts with pre-replication complex (pre-RC) subunits, designated
      Armadillo BTB Arabidopsis protein 1 (ABAP1). Overexpression of ABAP1 in plants
      limited mitotic DNA replication and decreased cell proliferation in leaves,
      whereas ABAP1 downregulation increased cell division rates. Activity of ABAP1 in
      transcription was supported by its association with the transcription factor
      AtTCP24. The ABAP1-AtTCP24 complex bound specifically to the promoters of AtCDT1a
      and AtCDT1b in vitro and in vivo. Moreover, expression levels of AtCDT1a and
      AtCDT1b were reduced in ABAP1-overexpressing plants and they were increased in
      plants with reduced levels of ABAP1. We propose that ABAP1 participates in a
      negative feedback loop regulating mitotic DNA replication during leaf
      development, either by repressing transcription of pre-RC genes and possibly by
      regulating pre-RC utilization through direct association with pre-RC components.

PMID- 18818696
TI  - Structural and functional coupling of Hsp90- and Sgt1-centred multi-protein
      complexes.
AB  - Sgt1 is an adaptor protein implicated in a variety of processes, including
      formation of the kinetochore complex in yeast, and regulation of innate immunity
      systems in plants and animals. Sgt1 has been found to associate with SCF E3
      ubiquitin ligases, the CBF3 kinetochore complex, plant R proteins and related
      animal Nod-like receptors, and with the Hsp90 molecular chaperone. We have
      determined the crystal structure of the core Hsp90-Sgt1 complex, revealing a
      distinct site of interaction on the Hsp90 N-terminal domain. Using the structure,
      we developed mutations in Sgt1 interfacial residues, which specifically abrogate
      interaction with Hsp90, and disrupt Sgt1-dependent functions in vivo, in plants
      and yeast. We show that Sgt1 bridges the Hsp90 molecular chaperone system to the
      substrate-specific arm of SCF ubiquitin ligase complexes, suggesting a role in
      SCF assembly and regulation, and providing multiple complementary routes for
      ubiquitination of Hsp90 client proteins.

PMID- 18818697
TI  - Protein co-evolution, co-adaptation and interactions.
AB  - Co-evolution has an important function in the evolution of species and it is
      clearly manifested in certain scenarios such as host-parasite and predator-prey
      interactions, symbiosis and mutualism. The extrapolation of the concepts and
      methodologies developed for the study of species co-evolution at the molecular
      level has prompted the development of a variety of computational methods able to
      predict protein interactions through the characteristics of co-evolution.
      Particularly successful have been those methods that predict interactions at the
      genomic level based on the detection of pairs of protein families with similar
      evolutionary histories (similarity of phylogenetic trees: mirrortree). Future
      advances in this field will require a better understanding of the molecular basis
      of the co-evolution of protein families. Thus, it will be important to decipher
      the molecular mechanisms underlying the similarity observed in phylogenetic trees
      of interacting proteins, distinguishing direct specific molecular interactions
      from other general functional constraints. In particular, it will be important to
      separate the effects of physical interactions within protein complexes ('co
      adaptation') from other forces that, in a less specific way, can also create
      general patterns of co-evolution.

PMID- 18818698
TI  - Structural insights into mechanism and specificity of O-GlcNAc transferase.
AB  - Post-translational modification of protein serines/threonines with N
      acetylglucosamine (O-GlcNAc) is dynamic, inducible and abundant, regulating many
      cellular processes by interfering with protein phosphorylation. O-GlcNAcylation
      is regulated by O-GlcNAc transferase (OGT) and O-GlcNAcase, both encoded by
      single, essential, genes in metazoan genomes. It is not understood how OGT
      recognises its sugar nucleotide donor and performs O-GlcNAc transfer onto
      proteins/peptides, and how the enzyme recognises specific cellular protein
      substrates. Here, we show, by X-ray crystallography and mutagenesis, that OGT
      adopts the (metal-independent) GT-B fold and binds a UDP-GlcNAc analogue at the
      bottom of a highly conserved putative peptide-binding groove, covered by a mobile
      loop. Strikingly, the tetratricopeptide repeats (TPRs) tightly interact with the
      active site to form a continuous 120 A putative interaction surface, whereas the
      previously predicted phosphatidylinositide-binding site locates to the opposite
      end of the catalytic domain. On the basis of the structure, we identify
      truncation/point mutants of the TPRs that have differential effects on activity
      towards proteins/peptides, giving first insights into how OGT may recognise its
      substrates.

PMID- 18818699
TI  - The addition of rituximab to front-line therapy with CHOP (R-CHOP) results in a
      higher response rate and longer time to treatment failure in patients with
      lymphoplasmacytic lymphoma: results of a randomized trial of the German Low-Grade
      Lymphoma Study Group (GLSG).
AB  - Lymphoplasmacytic lymphoma (LPL) is an indolent lymphoma with moderate
      sensitivity to conventional chemotherapy. This study investigated whether the
      addition of rituximab to standard chemotherapy improves treatment outcome in LPL
      and the subgroup of LPL patients fulfilling the criteria of Waldenstroem's
      macroglobulinemia (WM). A total of 69 patients with previously untreated LPL were
      enrolled into the trial; 64 patients were evaluable for treatment outcome. In
      all, 48 of the 64 LPL patients fulfilled the criteria of WM. Patients were
      randomly assigned to R-CHOP (rituximab, cyclophosphamide, doxorubicin,
      vincristine and prednisone, n=34) or CHOP (n=30). R-CHOP resulted in
      significantly higher overall response (OR) rate (94 vs 67%, P=0.0085) in the LPL
      patients and in the WM subgroup (91 vs 60%, P=0.0188). With a median observation
      time of 42 months, R-CHOP induced a significantly longer time to treatment
      failure (TTF) with a median of 63 months for R-CHOP vs 22 months in the CHOP arm
      in the LPL patients (P=0.0033) and in the WM subgroup (P=0.0241). There was no
      major difference of treatment-associated toxicity between both treatment groups.
      These data indicate that the addition of rituximab to front-line chemotherapy
      improves treatment outcome in patients with LPL or WM.

PMID- 18818700
TI  - A subset of Binet stage A CLL patients with TP53 abnormalities and mutated IGHV
      genes have stable disease.

PMID- 18818701
TI  - UPD1p indicates the presence of MPL W515L mutation in RARS-T, a mechanism
      analogous to UPD9p and JAK2 V617F mutation.

PMID- 18818702
TI  - Genome profiling of acute myelomonocytic leukemia: alteration of the MYB locus in
      MYST3-linked cases.
AB  - The t(8;16)(p11;p13) is a rare translocation involved in de novo and therapy
      related myelomonocytic and monocytic acute leukemia. It fuses two genes encoding
      histone acetyltransferases (HATs), MYST3 located at 8p11 to CREBBP located at
      16p13. Variant translocations involve other HAT-encoding genes such as EP300,
      MYST4, NCOA2 or NCOA3. MYST3-linked acute myeloid leukemias (AMLs) share specific
      clinical and biological features and a poor prognosis. Because of its rarity, the
      molecular biology of MYST3-linked AMLs remains poorly understood. We have
      established the genome and gene expression profiles of a multicentric series of
      61 M4/M5 AMLs including 18 MYST3-linked AMLs by using array comparative genome
      hybridization (aCGH) (n=52) and DNA microarrays (n=44), respectively. We show
      that M4/5 AMLs have a variety of rare genomic alterations. One alteration, a gain
      of the MYB locus, was found recurrently and only in the MYST3-linked AMLs (7/18
      vs 0/34). MYST3-AMLs have also a specific a gene expression profile, which
      includes overexpression of MYB, CD4 and HOXA genes. These features, reminiscent
      of T-cell acute lymphoid leukemia (ALL), suggest the targeting of a common T
      myeloid progenitor.

PMID- 18818703
TI  - beta-Catenin is essential for survival of leukemic stem cells insensitive to
      kinase inhibition in mice with BCR-ABL-induced chronic myeloid leukemia.
AB  - Philadelphia chromosome-positive (Ph(+)) chronic myeloid leukemia (CML) induced
      by the BCR-ABL oncogene is believed to be developed from leukemic stem cells
      (LSCs), and we have previously shown in mice that LSCs for CML express the same
      cell surface markers that are also expressed on normal hematopoietic stem cells
      (HSCs). Although the inhibition of BCR-ABL kinase activity by imatinib is highly
      effective in treating human Ph(+) CML in chronic phase, it is difficult to
      achieve molecular remission of the disease, suggesting that LSCs remain in
      patients. In this study, we find that following imatinib treatment, LSCs not only
      remained but also accumulated increasingly in bone marrow of CML mice. This
      insensitivity of LSCs to imatinib was not because of the lack of BCR-ABL kinase
      inhibition by imatinib, and proliferating leukemic cells derived from LSCs were
      still sensitive to growth inhibition by imatinib. These results identify an LSC
      survival pathway that is not inhibited by imatinib. Furthermore, we show that
      beta-catenin in the Wnt signaling pathway is essential for survival and self
      renewal of LSCs, providing a new strategy for targeting these cells.

PMID- 18818704
TI  - 17p13/TP53 deletion in B-CLL patients is associated with microRNA-34a
      downregulation.

PMID- 18818705
TI  - Survivin expression in the bone marrow of patients with severe congenital
      neutropenia.

PMID- 18818706
TI  - A novel translocation, t(14;19)(q32;p13), involving IGH@ and the cytokine
      receptor for erythropoietin.

PMID- 18818707
TI  - Factors influencing survival after relapse from acute lymphoblastic leukemia: a
      Children's Oncology Group study.
AB  - Despite great progress in curing childhood acute lymphoblastic leukemia (ALL),
      survival after relapse remains poor. We analyzed survival after relapse among
      9585 pediatric patients enrolled on Children's Oncology Group clinical trials
      between 1988 and 2002. A total of 1961 patients (20.5%) experienced relapse at
      any site. The primary end point was survival. Patients were subcategorized by the
      site of relapse and timing of relapse from initial diagnosis. Time to relapse
      remains the strongest predictor of survival. Patients experiencing early relapse
      less than 18 months from initial diagnosis had a particularly poor outcome with a
      5-year survival estimate of 21.0+/-1.8%. Standard risk patients who relapsed had
      improved survival compared with their higher risk counterparts; differences in
      survival for the two risk groups was most pronounced for patients relapsing after
      18 months. Adjusting for both time and relapse site, multivariate analysis showed
      that age (10+ years) and the presence of central nervous system disease at
      diagnosis, male gender, and T-cell disease were significant predictors of
      inferior post-relapse survival. It can be noted that there was no difference in
      survival rates for relapsed patients in earlier vs later era trials. New
      therapeutic strategies are urgently needed for children with relapsed ALL and
      efforts should focus on discovering the biological pathways that mediate drug
      resistance.

PMID- 18818708
TI  - Intravenous injection of siRNA directed against hypoxia-inducible factors
      prolongs survival in a Lewis lung carcinoma cancer model.
AB  - Different routes for the in vivo administration of synthetic siRNA complexes
      targeting lung tumors were compared, and siRNA complexes were administered for
      the inhibition of hypoxia-inducible factor (HIF-1alpha and HIF-2alpha).
      Intravenous jugular vein injection of siRNA proved to be the most effective means
      of targeting lung tumor tissue in the Lewis lung carcinoma (LLC1) model. In
      comparison, intraperitoneal injection of siRNA was not suitable for targeting of
      lung tumor and intratracheal administration of siRNA exclusively targeted
      macrophages. Inhibition of HIF-1alpha and HIF-2alpha by siRNA injected
      intravenously was validated by immunohistofluorescent analysis for glucose
      transporter-1 (GLUT-1), a well-established HIF target protein. The GLUT-1 signal
      was strongly attenuated in the lung tumors of mice treated with siRNA-targeting
      HIF-1alpha and HIF-2alpha, compared with mice treated with control siRNA.
      Interestingly, injection of siRNA directed against HIF-1alpha and HIF-2alpha into
      LLC1 lung tumor-bearing mice resulted in prolonged survival. Immunohistological
      analysis of the lung tumors from mice treated with siRNA directed against HIF
      1alpha and HIF-2alpha displayed reduced proliferation, angiogenesis and
      apoptosis, cellular responses, which are known to be affected by HIF. In
      conclusion, intravenous jugular vein injection of siRNA strongly targets the lung
      tumor and is effective in gene inhibition as demonstrated for HIF-1alpha and HIF
      2alpha.

PMID- 18818709
TI  - Exploiting the tumor microenvironment in the development of targeted cancer gene
      therapy.
AB  - The future success of cancer gene therapy is critically dependent upon the
      development of safe, practical and effective targeting strategies. In this study,
      we describe a novel and broadly applicable targeting approach in which the
      induction of apoptotic tumor cell death is linked to the differential expression
      within the tumor microenvironment of elevated levels of the pro-angiogenic
      cytokine vascular endothelial growth factor (VEGF). As VEGF is generally absent
      or produced at only low levels in most normal tissues, undesirable toxicity will
      not result even if the therapeutic gene in question is inadvertently expressed in
      non-targeted tissue sites. The basic approach makes use of a chimeric cell
      surface protein in which the membrane-spanning and cytoplasmic 'death domain' of
      the pro-apoptotic protein Fas are fused in frame to the extracellular ligand
      binding domain of the VEGF receptor Flk-1/KDR/VEGFR2 (Flk-1/Fas). The resultant
      chimeric Flk-1/Fas receptor was found to be stable and capable of inducing a
      rapid apoptotic response when expressed in tumor cells that produce endogenous
      VEGF. Importantly, in the absence of VEGF, transduced tumor cells remain viable
      although they can be triggered to die by the addition of recombinant VEGF. Given
      the key role played by VEGF in tumor development and progression, it is proposed
      that the Flk-1/Fas chimera may have great potential in the context of tumor cell
      targeted cancer gene therapy.

PMID- 18818710
TI  - E1A, E1B double-restricted replicative adenovirus at low dose greatly augments
      tumor-specific suicide gene therapy for gallbladder cancer.
AB  - Combination therapy with replicative oncolytic viruses is a recent topic in
      innovative cancer therapy, but few studies have examined the efficacy of
      oncolytic adenovirus plus replication-deficient adenovirus carrying a suicide
      gene. We aim to evaluate whether an E1A, E1B double-restricted oncolytic
      adenovirus, AxdAdB-3, can improve the efficacy for gallbladder cancers (GBCs) of
      the replication-deficient adenovirus-based herpes simplex virus thymidine kinase
      (HSVtk)/ganciclovir (GCV) therapy directed by the carcinoembryonic antigen (CEA)
      promoter. Cytopathic effects of AxdAdB-3 plus AxCEAprTK (an adenovirus expressing
      HSVtk directed by CEA promoter) or AxCAHSVtk (an adenovirus expressing HSVtk
      directed by a nonspecific CAG promoter) with GCV administration were examined in
      several GBC lines and normal cells. Efficacy in vivo was tested in severe
      combined immunodeficiency disease mice with GBC xenografts. Addition of AxdAdB-3
      (1 multiplicity of infection, MOI) significantly enhanced the cytopathic effects
      of AxCEAprTK (10 MOI)/GCV on GBC cells. The augmented effect was attributable to
      the replication of the AxCEAprTK and also to the enhanced CEA promoter activity,
      which was presumably transactivated by E1A. In normal cells, AxdAdB-3 (20 MOI)
      plus AxCEAprTK (200 MOI)/GCV was not cytopathic, whereas AxdAdB-3 (1 MOI) plus
      AxCAHSVtk (10 MOI)/GCV was significantly toxic. Low-dose AxdAdB-3 (2 x 10(7) PFU,
      plaque-forming unit) plus AxCEAprTK (2 x 10(8) PFU)/GCV significantly suppressed
      the growth of GBC xenografts as compared with either AxdAdB-3 (2 x 10(7) PFU)/GCV
      or AxCEAprTK (2 x 10(9) PFU)/GCV alone. E1A, E1B double-restricted replicating
      adenovirus at low dose significantly augmented the efficacy of CEA promoter
      directed HSVtk/GCV therapy without obvious toxicity to normal cells, suggesting a
      potential use of this combination for treating GBC and other CEA-producing
      malignancies.

PMID- 18818711
TI  - Spatial distribution of Bacteria and Archaea and amoA gene copy numbers
      throughout the water column of the Eastern Mediterranean Sea.
AB  - Until recently, ammonia oxidation, a key process in the global nitrogen cycle,
      was thought to be mediated exclusively by a few bacterial groups. It has been
      shown now, that also Crenarchaeota are capable to perform this initial
      nitrification step. The abundance of ammonia oxidizing Bacteria and Archaea was
      determined using the bacterial and archaeal ammonia monooxygenase-alpha subunit
      (amoA) gene as functional markers in a quantitative PCR approach and related to
      the abundance of Bacteria and Archaea in the Eastern Mediterranean Sea. Archaeal
      amoA copy numbers decreased from 4000-5000 copies ml(-1) seawater from the 200
      500 m depth layer to 20 copies ml(-1) at 1000 m depth. Beta-proteobacterial amoA
      genes were below the detection limit in all the samples. The archaeal amoA copy
      numbers were correlated with NO(2)(-) concentrations, suggesting that ammonia
      oxidizing Archaea may play a significant role in the nitrification in the
      mesopelagic waters of the Eastern Mediterranean Sea. In the bathypelagic waters,
      however, archaeal amoA gene abundance was rather low although Crenarchaeota were
      abundant, indicating that Crenarchaeota might largely lack the amoA gene in these
      deep waters. Terminal restriction fragment length polymorphism analysis of the
      archaeal community revealed a distinct clustering with the mesopelagic community
      distinctly different from the archaeal communities of both, the surface waters
      and the 3000-4000 m layers. Hence, the archaeal community in the Eastern
      Mediterranean Sea appears to be highly stratified despite the absence of major
      temperature and density gradients between the meso- and bathypelagic waters of
      the Mediterranean Sea.

PMID- 18818712
TI  - New handles on genomic structural variation.

PMID- 18818713
TI  - Kidney disease and African ancestry.

PMID- 18818714
TI  - Pristionchus pacificus: an appropriate fondness for beetles.

PMID- 18818715
TI  - Casting an eye on the Krebs cycle.

PMID- 18818716
TI  - Kras and Hras--what is the difference?

PMID- 18818718
TI  - Victor McKusick, 1921--2008: the founder of medical genetics as we know it.

PMID- 18818719
TI  - Advanced genomic data mining.

PMID- 18818720
TI  - Structure-guided comparative analysis of proteins: principles, tools, and
      applications for predicting function.

PMID- 18818721
TI  - Structural biology by NMR: structure, dynamics, and interactions.
AB  - The function of bio-macromolecules is determined by both their 3D structure and
      conformational dynamics. These molecules are inherently flexible systems
      displaying a broad range of dynamics on time-scales from picoseconds to seconds.
      Nuclear Magnetic Resonance (NMR) spectroscopy has emerged as the method of choice
      for studying both protein structure and dynamics in solution. Typically, NMR
      experiments are sensitive both to structural features and to dynamics, and hence
      the measured data contain information on both. Despite major progress in both
      experimental approaches and computational methods, obtaining a consistent view of
      structure and dynamics from experimental NMR data remains a challenge. Molecular
      dynamics simulations have emerged as an indispensable tool in the analysis of NMR
      data.

PMID- 18818722
TI  - Protein meta-functional signatures from combining sequence, structure, evolution,
      and amino acid property information.
AB  - Protein function is mediated by different amino acid residues, both their
      positions and types, in a protein sequence. Some amino acids are responsible for
      the stability or overall shape of the protein, playing an indirect role in
      protein function. Others play a functionally important role as part of active or
      binding sites of the protein. For a given protein sequence, the residues and
      their degree of functional importance can be thought of as a signature
      representing the function of the protein. We have developed a combination of
      knowledge- and biophysics-based function prediction approaches to elucidate the
      relationships between the structural and the functional roles of individual
      residues and positions. Such a meta-functional signature (MFS), which is a
      collection of continuous values representing the functional significance of each
      residue in a protein, may be used to study proteins of known function in greater
      detail and to aid in experimental characterization of proteins of unknown
      function. We demonstrate the superior performance of MFS in predicting protein
      functional sites and also present four real-world examples to apply MFS in a wide
      range of settings to elucidate protein sequence-structure-function relationships.
      Our results indicate that the MFS approach, which can combine multiple sources of
      information and also give biological interpretation to each component, greatly
      facilitates the understanding and characterization of protein function.

PMID- 18818723
TI  - Adaptation and selective information transmission in the cricket auditory neuron
      AN2.
AB  - Sensory systems adapt their neural code to changes in the sensory environment,
      often on multiple time scales. Here, we report a new form of adaptation in a
      first-order auditory interneuron (AN2) of crickets. We characterize the response
      of the AN2 neuron to amplitude-modulated sound stimuli and find that adaptation
      shifts the stimulus-response curves toward higher stimulus intensities, with a
      time constant of 1.5 s for adaptation and recovery. The spike responses were thus
      reduced for low-intensity sounds. We then address the question whether adaptation
      leads to an improvement of the signal's representation and compare the
      experimental results with the predictions of two competing hypotheses: infomax,
      which predicts that information conveyed about the entire signal range should be
      maximized, and selective coding, which predicts that "foreground" signals should
      be enhanced while "background" signals should be selectively suppressed. We test
      how adaptation changes the input-response curve when presenting signals with two
      or three peaks in their amplitude distributions, for which selective coding and
      infomax predict conflicting changes. By means of Bayesian data analysis, we
      quantify the shifts of the measured response curves and also find a slight
      reduction of their slopes. These decreases in slopes are smaller, and the
      absolute response thresholds are higher than those predicted by infomax. Most
      remarkably, and in contrast to the infomax principle, adaptation actually reduces
      the amount of encoded information when considering the whole range of input
      signals. The response curve changes are also not consistent with the selective
      coding hypothesis, because the amount of information conveyed about the loudest
      part of the signal does not increase as predicted but remains nearly constant.
      Less information is transmitted about signals with lower intensity.

PMID- 18818724
TI  - Natural selection fails to optimize mutation rates for long-term adaptation on
      rugged fitness landscapes.
AB  - The rate of mutation is central to evolution. Mutations are required for
      adaptation, yet most mutations with phenotypic effects are deleterious. As a
      consequence, the mutation rate that maximizes adaptation will be some
      intermediate value. Here, we used digital organisms to investigate the ability of
      natural selection to adjust and optimize mutation rates. We assessed the optimal
      mutation rate by empirically determining what mutation rate produced the highest
      rate of adaptation. Then, we allowed mutation rates to evolve, and we evaluated
      the proximity to the optimum. Although we chose conditions favorable for mutation
      rate optimization, the evolved rates were invariably far below the optimum across
      a wide range of experimental parameter settings. We hypothesized that the reason
      that mutation rates evolved to be suboptimal was the ruggedness of fitness
      landscapes. To test this hypothesis, we created a simplified landscape without
      any fitness valleys and found that, in such conditions, populations evolved near
      optimal mutation rates. In contrast, when fitness valleys were added to this
      simple landscape, the ability of evolving populations to find the optimal
      mutation rate was lost. We conclude that rugged fitness landscapes can prevent
      the evolution of mutation rates that are optimal for long-term adaptation. This
      finding has important implications for applied evolutionary research in both
      biological and computational realms.

PMID- 18818725
TI  - A genomewide functional network for the laboratory mouse.
AB  - Establishing a functional network is invaluable to our understanding of gene
      function, pathways, and systems-level properties of an organism and can be a
      powerful resource in directing targeted experiments. In this study, we present a
      functional network for the laboratory mouse based on a Bayesian integration of
      diverse genetic and functional genomic data. The resulting network includes
      probabilistic functional linkages among 20,581 protein-coding genes. We show that
      this network can accurately predict novel functional assignments and network
      components and present experimental evidence for predictions related to Nanog
      homeobox (Nanog), a critical gene in mouse embryonic stem cell pluripotency. An
      analysis of the global topology of the mouse functional network reveals multiple
      biologically relevant systems-level features of the mouse proteome. Specifically,
      we identify the clustering coefficient as a critical characteristic of central
      modulators that affect diverse pathways as well as genes associated with
      different phenotype traits and diseases. In addition, a cross-species comparison
      of functional interactomes on a genomic scale revealed distinct functional
      characteristics of conserved neighborhoods as compared to subnetworks specific to
      higher organisms. Thus, our global functional network for the laboratory mouse
      provides the community with a key resource for discovering protein functions and
      novel pathway components as well as a tool for exploring systems-level
      topological and evolutionary features of cellular interactomes. To facilitate
      exploration of this network by the biomedical research community, we illustrate
      its application in function and disease gene discovery through an interactive,
      Web-based, publicly available interface at http://mouseNET.princeton.edu.

PMID- 18818726
TI  - Spatial bistability generates hunchback expression sharpness in the Drosophila
      embryo.
AB  - During embryonic development, the positional information provided by
      concentration gradients of maternal factors directs pattern formation by
      providing spatially dependent cues for gene expression. In the fruit fly,
      Drosophila melanogaster, a classic example of this is the sharp on-off activation
      of the hunchback (hb) gene at midembryo, in response to local concentrations of
      the smooth anterior-posterior Bicoid (Bcd) gradient. The regulatory region for hb
      contains multiple binding sites for the Bcd protein as well as multiple binding
      sites for the Hb protein. Some previous studies have suggested that Bcd is
      sufficient for properly sharpened Hb expression, yet other evidence suggests a
      need for additional regulation. We experimentally quantified the dynamics of hb
      gene expression in flies that were wild-type, were mutant for hb self-regulation
      or Bcd binding, or contained an artificial promoter construct consisting of six
      Bcd and two Hb sites. In addition to these experiments, we developed a reaction
      diffusion model of hb transcription, with Bcd cooperative binding and hb self
      regulation, and used Zero Eigenvalue Analysis to look for multiple stationary
      states in the reaction network. Our model reproduces the hb developmental
      dynamics and correctly predicts the mutant patterns. Analysis of our model
      indicates that the Hb sharpness can be produced by spatial bistability, in which
      hb self-regulation produces two stable levels of expression. In the absence of
      self-regulation, the bistable behavior vanishes and Hb sharpness is disrupted.
      Bcd cooperative binding affects the position where bistability occurs but is not
      itself sufficient for a sharp Hb pattern. Our results show that the control of Hb
      sharpness and positioning, by hb self-regulation and Bcd cooperativity,
      respectively, are separate processes that can be altered independently. Our
      model, which matches the changes in Hb position and sharpness observed in
      different experiments, provides a theoretical framework for understanding the
      data and in particular indicates that spatial bistability can play a central role
      in threshold-dependent reading mechanisms of positional information.

PMID- 18818727
TI  - A dual receptor crosstalk model of G-protein-coupled signal transduction.
AB  - Macrophage cells that are stimulated by two different ligands that bind to G
      protein-coupled receptors (GPCRs) usually respond as if the stimulus effects are
      additive, but for a minority of ligand combinations the response is synergistic.
      The G-protein-coupled receptor system integrates signaling cues from the
      environment to actuate cell morphology, gene expression, ion homeostasis, and
      other physiological states. We analyze the effects of the two signaling molecules
      complement factors 5a (C5a) and uridine diphosphate (UDP) on the intracellular
      second messenger calcium to elucidate the principles that govern the processing
      of multiple signals by GPCRs. We have developed a formal hypothesis, in the form
      of a kinetic model, for the mechanism of action of this GPCR signal transduction
      system using data obtained from RAW264.7 macrophage cells. Bayesian statistical
      methods are employed to represent uncertainty in both data and model parameters
      and formally tie the model to experimental data. When the model is also used as a
      tool in the design of experiments, it predicts a synergistic region in the
      calcium peak height dose response that results when cells are simultaneously
      stimulated by C5a and UDP. An analysis of the model reveals a potential mechanism
      for crosstalk between the Galphai-coupled C5a receptor and the Galphaq-coupled
      UDP receptor signaling systems that results in synergistic calcium release.

PMID- 18818728
TI  - A review of family-based tests for linkage disequilibrium between a quantitative
      trait and a genetic marker.
AB  - Quantitative trait transmission/disequilibrium tests (quantitative TDTs) are
      commonly used in family-based genetic association studies of quantitative traits.
      Despite the availability of various quantitative TDTs, some users are not aware
      of the properties of these tests and the relationships between them. This review
      aims at outlining the broad features of the various quantitative TDT procedures
      carried out in the frequently used QTDT and FBAT packages. Specifically, we
      discuss the "Rabinowitz" and the "Monks-Kaplan" procedures, as well as the
      various "Abecasis" and "Allison" regression-based procedures. We focus on the
      models assumed in these tests and the relationships between them. Moreover, we
      discuss what hypotheses are tested by the various quantitative TDTs, what testing
      procedures are best suited to various forms of data, and whether the regression
      based tests overcome population stratification problems. Finally, we comment on
      power considerations in the choice of the test to be used. We hope this brief
      review will shed light on the similarities and differences of the various
      quantitative TDTs.

PMID- 18818729
TI  - Gene-boosted assembly of a novel bacterial genome from very short reads.
AB  - Recent improvements in technology have made DNA sequencing dramatically faster
      and more efficient than ever before. The new technologies produce highly accurate
      sequences, but one drawback is that the most efficient technology produces the
      shortest read lengths. Short-read sequencing has been applied successfully to
      resequence the human genome and those of other species but not to whole-genome
      sequencing of novel organisms. Here we describe the sequencing and assembly of a
      novel clinical isolate of Pseudomonas aeruginosa, strain PAb1, using very short
      read technology. From 8,627,900 reads, each 33 nucleotides in length, we
      assembled the genome into one scaffold of 76 ordered contiguous sequences
      containing 6,290,005 nucleotides, including one contig spanning 512,638
      nucleotides, plus an additional 436 unordered contigs containing 416,897
      nucleotides. Our method includes a novel gene-boosting algorithm that uses amino
      acid sequences from predicted proteins to build a better assembly. This study
      demonstrates the feasibility of very short read sequencing for the sequencing of
      bacterial genomes, particularly those for which a related species has been
      sequenced previously, and expands the potential application of this new
      technology to most known prokaryotic species.

PMID- 18818730
TI  - PLoS Pathogens at three years.

PMID- 18818731
TI  - FtsK-dependent dimer resolution on multiple chromosomes in the pathogen Vibrio
      cholerae.
AB  - Unlike most bacteria, Vibrio cholerae harbors two distinct, nonhomologous
      circular chromosomes (chromosome I and II). Many features of chromosome II are
      plasmid-like, which raised questions concerning its chromosomal nature. Plasmid
      replication and segregation are generally not coordinated with the bacterial cell
      cycle, further calling into question the mechanisms ensuring the synchronous
      management of chromosome I and II. Maintenance of circular replicons requires the
      resolution of dimers created by homologous recombination events. In Escherichia
      coli, chromosome dimers are resolved by the addition of a crossover at a specific
      site, dif, by two tyrosine recombinases, XerC and XerD. The process is
      coordinated with cell division through the activity of a DNA translocase, FtsK.
      Many E. coli plasmids also use XerCD for dimer resolution. However, the process
      is FtsK-independent. The two chromosomes of the V. cholerae N16961 strain carry
      divergent dimer resolution sites, dif1 and dif2. Here, we show that V. cholerae
      FtsK controls the addition of a crossover at dif1 and dif2 by a common pair of
      Xer recombinases. In addition, we show that specific DNA motifs dictate its
      orientation of translocation, the distribution of these motifs on chromosome I
      and chromosome II supporting the idea that FtsK translocation serves to bring
      together the resolution sites carried by a dimer at the time of cell division.
      Taken together, these results suggest that the same FtsK-dependent mechanism
      coordinates dimer resolution with cell division for each of the two V. cholerae
      chromosomes. Chromosome II dimer resolution thus stands as a bona fide
      chromosomal process.

PMID- 18818732
TI  - Evolutionary dynamics and emergence of panzootic H5N1 influenza viruses.
AB  - The highly pathogenic avian influenza (HPAI) H5N1 virus lineage has undergone
      extensive genetic reassortment with viruses from different sources to produce
      numerous H5N1 genotypes, and also developed into multiple genetically distinct
      sublineages in China. From there, the virus has spread to over 60 countries. The
      ecological success of this virus in diverse species of both poultry and wild
      birds with frequent introduction to humans suggests that it is a likely source of
      the next human pandemic. Therefore, the evolutionary and ecological
      characteristics of its emergence from wild birds into poultry are of considerable
      interest. Here, we apply the latest analytical techniques to infer the early
      evolutionary dynamics of H5N1 virus in the population from which it emerged (wild
      birds and domestic poultry). By estimating the time of most recent common
      ancestors of each gene segment, we show that the H5N1 prototype virus was likely
      introduced from wild birds into poultry as a non-reassortant low pathogenic avian
      influenza H5N1 virus and was not generated by reassortment in poultry. In
      contrast, more recent H5N1 genotypes were generated locally in aquatic poultry
      after the prototype virus (A/goose/Guangdong/1/96) introduction occurred, i.e.,
      they were not a result of additional emergence from wild birds. We show that the
      H5N1 virus was introduced into Indonesia and Vietnam 3-6 months prior to
      detection of the first outbreaks in those countries. Population dynamics analyses
      revealed a rapid increase in the genetic diversity of A/goose/Guangdong/1/96
      lineage viruses from mid-1999 to early 2000. Our results suggest that the
      transmission of reassortant viruses through the mixed poultry population in farms
      and markets in China has selected HPAI H5N1 viruses that are well adapted to
      multiple hosts and reduced the interspecies transmission barrier of those
      viruses.

PMID- 18818733
TI  - The pseudomonas quinolone signal (PQS) balances life and death in Pseudomonas
      aeruginosa populations.
AB  - When environmental conditions deteriorate and become inhospitable, generic
      survival strategies for populations of bacteria may be to enter a dormant state
      that slows down metabolism, to develop a general tolerance to hostile parameters
      that characterize the habitat, and to impose a regime to eliminate damaged
      members. Here, we provide evidence that the pseudomonas quinolone signal (PQS)
      mediates induction of all of these phenotypes. For individual cells, PQS, an
      interbacterial signaling molecule of Pseudomonas aeruginosa, has both deleterious
      and beneficial activities: on the one hand, it acts as a pro-oxidant and
      sensitizes the bacteria towards oxidative and other stresses and, on the other,
      it efficiently induces a protective anti-oxidative stress response. We propose
      that this dual function fragments populations into less and more stress tolerant
      members which respond differentially to developing stresses in deteriorating
      habitats. This suggests that a little poison may be generically beneficial to
      populations, in promoting survival of the fittest, and in contributing to
      bacterial multi-cellular behavior. It further identifies PQS as an essential
      mediator of the shaping of the population structure of Pseudomonas and of its
      response to and survival in hostile environmental conditions.

PMID- 18818734
TI  - Interfering RNA and HIV: reciprocal interferences.
AB  - In this review, a quick presentation of what interfering RNA (iRNA) are--small
      RNA able to exert an inhibition on gene expression at a posttranscriptional
      level, based on sequence homology between the iRNA and the mRNA--will be given.
      The many faces of the interrelations between iRNA and viruses, particularly HIV,
      will be reviewed. Four kinds of interactions have been described: i) iRNA of
      viral origin blocking viral RNA, ii) iRNA of viral origin downregulating cellular
      mRNA, iii) iRNA of cellular origin (microRNA) targeting viral RNA, and iv)
      microRNA downregulating cellular mRNA encoding cell proteins used by the virus
      for its replication. Next, HIV strategies to manipulate these interrelations will
      be considered: suppression of iRNA biosynthesis by Tat, trapping by the HIV TAR
      sequence of a cell component, TRBP, necessary for iRNA production and action, and
      induction by the virus of some microRNA together with suppression of others.
      Then, we will discuss the putative effects of these mutual influences on viral
      replication as well as on viral latency, immune response, and viral
      cytopathogenicity. Finally, the potential consequences on the human infection of
      genetic polymorphisms in microRNA genes and the therapeutic potential of iRNA
      will be presented.

PMID- 18818735
TI  - Chromosome mechanics and meiotic engine maintenance.

PMID- 18818736
TI  - Capnocytophaga canimorsus: a human pathogen feeding at the surface of epithelial
      cells and phagocytes.
AB  - Capnocytophaga canimorsus, a commensal bacterium of the canine oral flora, has
      been repeatedly isolated since 1976 from severe human infections transmitted by
      dog bites. Here, we show that C. canimorsus exhibits robust growth when it is in
      direct contact with mammalian cells, including phagocytes. This property was
      found to be dependent on a surface-exposed sialidase allowing C. canimorsus to
      utilize internal aminosugars of glycan chains from host cell glycoproteins.
      Although sialidase probably evolved to sustain commensalism, by releasing
      carbohydrates from mucosal surfaces, it also contributed to bacterial persistence
      in a murine infection model: the wild type, but not the sialidase-deficient
      mutant, grew and persisted, both when infected singly or in competition. This
      study reveals an example of pathogenic bacteria feeding on mammalian cells,
      including phagocytes by deglycosylation of host glycans, and it illustrates how
      the adaptation of a commensal to its ecological niche in the host, here the dog's
      oral cavity, contributes to being a potential pathogen.

PMID- 18818737
TI  - Effect of Calendula officinalis Flower Extract on Acute Phase Proteins,
      Antioxidant Defense Mechanism and Granuloma Formation During Thermal Burns.
AB  - Effect of Calendula officinalis flower extract was investigated against
      experimentally induced thermal burns in rats. Burn injury was made on the shaven
      back of the rats under anesthesia and the animals were treated orally with
      different doses of the flower extract (20 mg, 100 mg and 200 mg/kg body weight).
      The animals treated with the extract showed significant improvement in healing
      when compared with the control untreated animals. The indicators of the wound
      healing such as collagen-hydroxyproline and hexosamine contents were
      significantly increased in the treated group indicating accelerated wound healing
      in the treated animals. The acute phase proteins-haptoglobin and orosomucoid
      which were increased due to burn injury were found to be decreased significantly
      in 200 mg/kg body weight extract treated animals. The antioxidant defense
      mechanism, which was decreased in the liver during burn injury, was found to be
      enhanced in treated animals. The lipid peroxidation was significantly lowered in
      the treated group when compared to control animals. Tissue damage marker enzymes-
      alkaline phosphatase, alanine and aspartate transaminases were significantly
      lowered in the treated groups in a dose dependant manner. The histopathological
      analyses of skin tissue also give the evidence of the increased healing potential
      of the extract after burn injury.

PMID- 18818738
TI  - Rapid identification of known and new RNA viruses from animal tissues.
AB  - Viral surveillance programs or diagnostic labs occasionally obtain infectious
      samples that fail to be typed by available cell culture, serological, or nucleic
      acid tests. Five such samples, originating from insect pools, skunk brain, human
      feces and sewer effluent, collected between 1955 and 1980, resulted in pathology
      when inoculated into suckling mice. In this study, sequence-independent
      amplification of partially purified viral nucleic acids and small scale shotgun
      sequencing was used on mouse brain and muscle tissues. A single viral agent was
      identified in each sample. For each virus, between 16% to 57% of the viral genome
      was acquired by sequencing only 42-108 plasmid inserts. Viruses derived from
      human feces or sewer effluent belonged to the Picornaviridae family and showed
      between 80% to 91% amino acid identities to known picornaviruses. The complete
      polyprotein sequence of one virus showed strong similarity to a simian
      picornavirus sequence in the provisional Sapelovirus genus. Insects and skunk
      derived viral sequences exhibited amino acid identities ranging from 25% to 98%
      to the segmented genomes of viruses within the Reoviridae family. Two isolates
      were highly divergent: one is potentially a new species within the orthoreovirus
      genus, and the other is a new species within the orbivirus genus. We demonstrate
      that a simple, inexpensive, and rapid metagenomics approach is effective for
      identifying known and highly divergent new viruses in homogenized tissues of
      acutely infected mice.

PMID- 18818739
TI  - Substrate binding mode and its implication on drug design for botulinum
      neurotoxin A.
AB  - The seven antigenically distinct serotypes of Clostridium botulinum neurotoxins,
      the causative agents of botulism, block the neurotransmitter release by
      specifically cleaving one of the three SNARE proteins and induce flaccid
      paralysis. The Centers for Disease Control and Prevention (CDC) has declared them
      as Category A biowarfare agents. The most potent among them, botulinum neurotoxin
      type A (BoNT/A), cleaves its substrate synaptosome-associated protein of 25 kDa
      (SNAP-25). An efficient drug for botulism can be developed only with the
      knowledge of interactions between the substrate and enzyme at the active site.
      Here, we report the crystal structures of the catalytic domain of BoNT/A with its
      uncleavable SNAP-25 peptide (197)QRATKM(202) and its variant (197)RRATKM(202) to
      1.5 A and 1.6 A, respectively. This is the first time the structure of an
      uncleavable substrate bound to an active botulinum neurotoxin is reported and it
      has helped in unequivocally defining S1 to S5' sites. These substrate peptides
      make interactions with the enzyme predominantly by the residues from 160, 200,
      250 and 370 loops. Most notably, the amino nitrogen and carbonyl oxygen of P1
      residue (Gln197) chelate the zinc ion and replace the nucleophilic water. The P1'
      Arg198, occupies the S1' site formed by Arg363, Thr220, Asp370, Thr215, Ile161,
      Phe163 and Phe194. The S2' subsite is formed by Arg363, Asn368 and Asp370, while
      S3' subsite is formed by Tyr251, Leu256, Val258, Tyr366, Phe369 and Asn388. P4'
      Lys201 makes hydrogen bond with Gln162. P5'-Met202 binds in the hydrophobic
      pocket formed by the residues from the 250 and 200 loop. Knowledge of
      interactions between the enzyme and substrate peptide from these complex
      structures should form the basis for design of potent inhibitors for this
      neurotoxin.

PMID- 18818740
TI  - Intronic Alus influence alternative splicing.
AB  - Examination of the human transcriptome reveals higher levels of RNA editing than
      in any other organism tested to date. This is indicative of extensive double
      stranded RNA (dsRNA) formation within the human transcriptome. Most of the
      editing sites are located in the primate-specific retrotransposed element called
      Alu. A large fraction of Alus are found in intronic sequences, implying extensive
      Alu-Alu dsRNA formation in mRNA precursors. Yet, the effect of these intronic
      Alus on splicing of the flanking exons is largely unknown. Here, we show that
      more Alus flank alternatively spliced exons than constitutively spliced ones;
      this is especially notable for those exons that have changed their mode of
      splicing from constitutive to alternative during human evolution. This implies
      that Alu insertions may change the mode of splicing of the flanking exons.
      Indeed, we demonstrate experimentally that two Alu elements that were inserted
      into an intron in opposite orientation undergo base-pairing, as evident by RNA
      editing, and affect the splicing patterns of a downstream exon, shifting it from
      constitutive to alternative. Our results indicate the importance of intronic Alus
      in influencing the splicing of flanking exons, further emphasizing the role of
      Alus in shaping of the human transcriptome.

PMID- 18818741
TI  - Csm4, in collaboration with Ndj1, mediates telomere-led chromosome dynamics and
      recombination during yeast meiosis.
AB  - Chromosome movements are a general feature of mid-prophase of meiosis. In budding
      yeast, meiotic chromosomes exhibit dynamic movements, led by nuclear envelope
      (NE)-associated telomeres, throughout the zygotene and pachytene stages. Zygotene
      motion underlies the global tendency for colocalization of NE-associated
      chromosome ends in a "bouquet." In this study, we identify Csm4 as a new
      molecular participant in these processes and show that, unlike the two previously
      identified components, Ndj1 and Mps3, Csm4 is not required for meiosis-specific
      telomere/NE association. Instead, it acts to couple telomere/NE ensembles to a
      force generation mechanism. Mutants lacking Csm4 and/or Ndj1 display the
      following closely related phenotypes: (i) elevated crossover (CO) frequencies and
      decreased CO interference without abrogation of normal pathways; (ii) delayed
      progression of recombination, and recombination-coupled chromosome morphogenesis,
      with resulting delays in the MI division; and (iii) nondisjunction of homologs at
      the MI division for some reason other than absence of (the obligatory) CO(s). The
      recombination effects are discussed in the context of a model where the
      underlying defect is chromosome movement, the absence of which results in
      persistence of inappropriate chromosome relationships that, in turn, results in
      the observed mutant phenotypes.

PMID- 18818742
TI  - Csm4-dependent telomere movement on nuclear envelope promotes meiotic
      recombination.
AB  - During meiotic prophase, chromosomes display rapid movement, and their telomeres
      attach to the nuclear envelope and cluster to form a "chromosomal bouquet."
      Little is known about the roles of the chromosome movement and telomere
      clustering in this phase. In budding yeast, telomere clustering is promoted by a
      meiosis-specific, telomere-binding protein, Ndj1. Here, we show that a meiosis
      specific protein, Csm4, which forms a complex with Ndj1, facilitates bouquet
      formation. In the absence of Csm4, Ndj1-bound telomeres tether to nuclear
      envelopes but do not cluster, suggesting that telomere clustering in the meiotic
      prophase consists of at least two distinct steps: Ndj1-dependent tethering to the
      nuclear envelope and Csm4-dependent clustering/movement. Similar to Ndj1, Csm4 is
      required for several distinct steps during meiotic recombination. Our results
      suggest that Csm4 promotes efficient second-end capture of a double-strand break
      following a homology search, as well as resolution of the double-Holliday
      junction during crossover formation. We propose that chromosome movement and
      associated telomere dynamics at the nuclear envelope promotes the completion of
      key biochemical steps during meiotic recombination.

PMID- 18818743
TI  - Enhanced Glucose Requirement in Human Hepatoma-derived HuH-7 Cells by Forced
      Expression of the bcl-2 Gene.
AB  - To explore the metabolic effects of Bcl-2 in tumor cells, a stable clone of HuH
      7/bcl-2 and its control HuH-7/neo were established. Mitochondrial localization of
      ectopic Bcl-2 was demonstrated both by western blotting and immunofluorescence.
      HuH-7/bcl-2 cells consumed glucose at a higher rate, exhausted the available
      cellular ATP and died on day 9, while HuH-7/neo cells were still alive for 10
      days under the same condition where cells were cultured without replenishment of
      the medium. The expression of the hexokinase II gene was up-regulated in HuH
      7/bcl-2 at its protein level. Taken together, we suggest that the forced
      expression of Bcl-2 in human hepatoma may cause the cells to become more glucose
      dependent for survival.

PMID- 18818744
TI  - Suppressive Effects of Selected Food Phytochemicals on CD74 Expression in NCI-N87
      Gastric Carcinoma Cells.
AB  - Helicobacter pylori (H. pylori) is one of the most widespread human pathogens,
      and plays major roles in chronic gastritis and gastric cancer. CD74 of gastric
      epithelial cells has recently been identified as an adhesion molecule to urease
      in H. pylori. In this study, we found that CD74 is highly expressed in a
      constitutive manner in NCI-N87 human gastric carcinoma cells at both the protein
      and mRNA levels as compared with Hs738St./Int fetal gastric cells. Subsequently,
      a novel cell-based ELISA able to rapidly screen the suppressive agents of CD74
      expression was established. NCI-N87 cells were treated separately with 25
      different food phytochemicals (4-100 microM) for 48 h and subjected to our novel
      assay. From those results, a citrus coumarin, bergamottin, was indicated to be
      the most promising compound with an LC(50)/IC(50) value greater than 7.1,
      followed by luteolin (>5.4), nobiletin (>5.3), and quercetin (>5.1). Our findings
      suggest that these CD74 suppressants are unique candidates for preventing H.
      pylori adhesion and subsequent infection with reasonable action mechanisms.

PMID- 18818745
TI  - Antioxidative and antimutagenic activities of 70% ethanolic extracts from four
      fungal mycelia-fermented specialty rices.
AB  - The health-promoting potential of 70% ethanolic extracts of 4 rice varieties
      fermented with Monascus ruber, Phellinus linteus, Cordyceps sinensis and Agaricus
      blazei was evaluated mainly focusing on their antioxidative and antimutagenic
      capacities based on the following parameters: phenolic compound and phytic acid
      content; inhibitory activity on lipid peroxidation; scavenging activity on DPPH
      radical; suppressing ability on mitomycin C-induced mutagenesis in E. coli cells;
      and protective effect on 4-nitroquinoline oxide-triggered DNA lesion in V79
      hamster cells. The fermented rice extracts were superior in overall health
      promoting parameters compared to the source material. The higher antimutagenic
      activity of the fermented rice extracts might be in part caused by a larger
      amount of antioxidant constituents such as phenolic compounds or phytic acid. Of
      the fungal species, Monascus ruber was found to impart a marked increase in both
      the antioxidative and antimutagenic abilities to the source material. The current
      study suggests a possibility that such fermented rice may contribute to the
      prevention of lifestyle-related diseases such as cancer through a daily intake of
      rice-based diets.

PMID- 18818748
TI  - Preterm birth in Caucasians is associated with coagulation and inflammation
      pathway gene variants.
AB  - Spontaneous preterm birth (<37 weeks gestation-PTB) occurs in approximately 12%
      of pregnancies in the United States, and is the largest contributor to neonatal
      morbidity and mortality. PTB is a complex disease, potentially induced by several
      etiologic factors from multiple pathophysiologic pathways. To dissect the genetic
      risk factors of PTB a large-scale high-throughput candidate gene association
      study was performed examining 1536 SNP in 130 candidate genes from hypothesized
      PTB pathways. Maternal and fetal DNA from 370 US Caucasian birth-events (172
      cases and 198 controls) was examined. Single locus, haplotype, and multi-locus
      association analyses were performed separately on maternal and fetal data. For
      maternal data the strongest associations were found in genes in the complement
      coagulation pathway related to decidual hemorrhage in PTB. In this pathway 3 of 6
      genes examined had SNPs significantly associated with PTB. These include factor V
      (FV) that was previously associated with PTB, factor VII (FVII), and tissue
      plasminogen activator (tPA). The single strongest effect was observed in tPA
      marker rs879293 with a significant allelic (p = 2.30x10(-3)) and genotypic
      association (p = 2.0x10(-6)) with PTB. The odds ratio (OR) for this SNP was 2.80
      [CI 1.77-4.44] for a recessive model. Given that 6 of 8 markers in tPA were
      statistically significant, sliding window haplotype analyses were performed and
      revealed an associating 4 marker haplotype in tPA (p = 6.00x10(-3)). The single
      strongest effect in fetal DNA was observed in the inflammatory pathway at
      rs17121510 in the interleukin-10 receptor antagonist (IL-10RA) gene for allele (p
      = 0.01) and genotype (p = 3.34x10(-4)). The OR for the IL-10RA genotypic additive
      model was 1.92 [CI 1.15-3.19] (p = 2.00x10(-3)). Finally, exploratory multi-locus
      analyses in the complement and coagulation pathway were performed and revealed a
      potentially significant interaction between a marker in FV (rs2187952) and FVII
      (rs3211719) (p<0.001). These results support a role for genes in both the
      coagulation and inflammation pathways, and potentially different maternal and
      fetal genetic risks for PTB.

PMID- 18818749
TI  - Essential roles of COUP-TFII in Leydig cell differentiation and male fertility.
AB  - Chicken Ovalbumin Upstream Promoter-Transcription Factor II (COUP-TFII; also
      known as NR2F2), is an orphan nuclear receptor of the steroid/thyroid hormone
      receptor superfamily. COUP-TFII-null mice die during the early embryonic
      development due to angiogenesis and cardiovascular defects. To circumvent the
      early embryonic lethality and investigate the physiological function of COUP
      TFII, we knocked out COUP-TFII gene in a time-specific manner by using a
      tamoxifen inducible Cre recombinase. The ablation of COUP-TFII during pre
      pubertal stages of male development results in infertility, hypogonadism and
      spermatogenetic arrest. Homozygous adult male mutants are defective in
      testosterone synthesis, and administration of testosterone could largely rescue
      the mutant defects. Notably, the rescued results also provide the evidence that
      the major function of adult Leydig cell is to synthesize testosterone. Further
      phenotypic analysis reveals that Leydig cell differentiation is arrested at the
      progenitor cell stage in the testes of null mice. The failure of testosterone to
      resumption of Leydig cell maturation in the null mice indicates that COUP-TFII
      itself is essential for this process. In addition, we identify that COUP-TFII
      plays roles in progenitor Leydig cell formation and early testis organogenesis,
      as demonstrated by the ablation of COUP-TFII at E18.5. On the other hand, when
      COUP-TFII is deleted in the adult stage after Leydig cells are well
      differentiated, there are no obvious defects in reproduction and Leydig cell
      function. Taken together, these results indicate that COUP-TFII plays a major
      role in differentiation, but not the maintenance of Leydig cells.

PMID- 18818751
TI  - Eicosapentaenoic Acid suppresses the proliferation of synoviocytes from
      rheumatoid arthritis.
AB  - Eicosapentaenoic acid (EPA) is essential for normal cell growth, and may play an
      important role in inflammatory and autoimmune disorders including rheumatoid
      arthritis. We investigate that EPA could suppress the proliferation of fibroblast
      like synoviocytes in vitro. We treated synoviocytes with 1 to 50 microM EPA and
      measured cell viabilities by the modified MTT assay. We sorted the number of them
      in sub G1 stage by fluorescence-activated cell sorting caliber. And we stained
      them by light green or Hoechst 33258, and investigate microscopic appearance. The
      cell viabilities were decreased at 30 microM, 40 microM, and 50 microM of EPA
      comparing to 0 microM of EPA. The half maximal concentration of synoviocytes
      inhibition was approximately 25 microM. At day 1 and day 3, cell number was also
      decreased at 50 microM EPA comparing to control. FACS caliber indicated the
      number of synoviocytes in sub G1 stage did not increase in each concentration of
      EPA. Hoechst staining indicated normal chromatin pattern and no change in a
      nuclear morphology both in EPA treated synoviocytes and in untreated
      synoviocytes. These findings suggest that EPA could suppress the proliferation of
      synoviocytes in vivo dose dependently and time dependently, however, the
      mechanism is not due to apoptosis.

PMID- 18818752
TI  - Effect of isoflavones on cardiovascular health: low but not out either.

PMID- 18818753
TI  - Regulation of cell survival and death signals induced by oxidative stress.
AB  - Oxidative stress stimulates two opposite signaling pathways leading to cell death
      and cell survival. Preferential selection of survival signals leads to the
      protection of cells against damage induced by reactive oxygen species, whereas
      preferential acceleration of death signals can be used to advantage in tumor
      therapy with oxidizing agents such as ionizing radiation and anticancer drugs. In
      vitro and in vivo experiments using cultured mammalian cells and experimental
      animals showed that ERK was included in survival signals and SAPK and p38 MAPK in
      death signals in oxidative stress. The activation of SAPK/JNK and subsequent
      expression of death receptor Fas on the cell surface caused the induction of cell
      death. The results mean that the acceleration of the activation of SAPK/JNK might
      lead to the enhancement of cell death by oxidizing agents like ionizing radiation
      and anticancer drugs. In fact, when cultured mammalian cells were exposed to
      ionizing radiation with 2-nitroimidazole derivatives having electrophilicity, the
      lethal effect of ionizing radiation was found to be enhanced together with the
      activation of SAPK/JNK and the enhancement of Fas expression. The activation of
      both survival and death signals was suppressed by the antioxidants N
      acetylcystein and Trolox, suggesting that both signaling pathways are redox
      regulated.

PMID- 18818754
TI  - Role of linoleic Acid hydroperoxide preformed by cyclooxygenase-1 or -2 on the
      regulation of prostaglandin formation from arachidonic Acid by the respective
      enzyme.
AB  - Linoleic acid (LA) preincubated with cyclooxygenase (COX)-1 or -2 inhibited
      prostaglandin (PG) formation from arachidonic acid (AA) catalyzed by the
      respective enzyme, but LA without the preincubation did not. 13S-Hydroperoxy
      9Z,11E-octadecadienoic acid (13-HPODE) a hydroperoxy adduct of LA inhibited PG
      formation catalyzed by COX-1 or -2. 13S-Hydroxy-9Z,11E-octadecadienoic acid had
      no effect on both COX-1 and -2 activities. These results suggest that 13-HPODE
      which is preformed from LA by COX reaction under normal physiological conditions
      can be a basal suppressor of PG formation from AA.

PMID- 18818755
TI  - Effects of astaxanthin on human blood rheology.
AB  - Effects of astaxanthin (AX) derived from H. pluvialis on human blood rheology
      were investigated in 20 adult men with a single-blind method. The experimental
      group was 57.5 +/- 9.8 years of age and the placebo group was 50.8 +/- 13.1 years
      of age. A blood rheology test that measures whole blood transit time was
      conducted using heparinized blood of the volunteers by a MC-FAN apparatus
      (microchannel array flow analyzer). After administration of AX 6 mg/day for 10
      days, the values of the experimental group were decreased from 52.8 +/- 4.9 s to
      47.6 +/- 4.2 s (p<0.01) and a comparison of the values between the experimental
      (47.6 +/- 4.2 s) and the placebo (54.2 +/- 6.7 s) groups showed a significant
      difference (p<0.05). There were no adverse effects resulting from the
      administration of AX 6 mg/day for 10 days. Informed consent was obtained from
      each subject.

PMID- 18818756
TI  - Fasting differentially modulates the immunological system: its mechanism and sex
      difference.
AB  - The immunological properties and hormonal metabolism in rodents are affected by
      physical and psychological stress more strongly in males than in females. To
      elucidate the mechanism and physiological significance of the sex difference in
      the susceptibility of animal to stresses, changes in the immunological system in
      plasma and intestine and hormonal status in plasma were compared among 8-week-old
      male and female ICR mice before and after fasting. During the fasting of animals,
      the expression of immunoglobulin A in intestinal mucosa, and cortisol,
      interleukin-10 and interferon-gamma in plasma increased. These changes occurred
      more apparently in males than in females. Under identical conditions, the plasma
      levels of testosterone decreased markedly with concomitant occurrence of
      apoptosis in the testis, while the plasma levels of estradiol decreased calmly,
      and no appreciable apoptosis occurred in the ovary. These results indicate that
      testosterone enhances the stress-induced modulation of the immune system by some
      mechanism that was antagonized by estradiol.

PMID- 18818757
TI  - Randomized controlled trial of two forms of self-management group education in
      Japanese people with impaired glucose tolerance.
AB  - The aim of this study was to determine the effectiveness of education on diabetes
      prevention in subjects with impaired glucose tolerance. A total of 100 subjects
      of impaired glucose tolerance with hemoglobin A1c (HbA1c) levels >/=5.5 to <6.1%
      were assigned randomly to either support or control groups. All subjects received
      education in 8 sessions over a 6-month period. The support group consisted of 10
      members collaborating with a dietitian or a nurse who learned coping skills by
      employing a participant-centered approach. Participants in the support group were
      required to keep a diary that monitored weight, food intake and blood glucose
      levels, while the control group attended several lectures. Subjects assigned to
      the support group had a reduction in mean HbA1c levels from 5.77 +/- 0.36% at
      baseline to 5.39 +/- 0.24% at the endpoint (p<0.01). Weight, total cholesterol
      (TC), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) levels
      also decreased (p<0.01) in the support group, whereas subjects in the control
      group had no observable reduction in these indices. After intervention,
      participants of the support group had improvements in their 2-h post-meal blood
      glucose levels. Support group education can be effective for improving glycemic
      control in participants when carried out in collaboration with educators and
      other team members.

PMID- 18818758
TI  - Lipid lowering effect of antioxidant alpha-lipoic Acid in experimental
      atherosclerosis.
AB  - Accumulating data demonstrated that hypercholesterolemia and oxidative stress
      play an important role in the development of atherosclerosis. In the present
      study, a protective activity of alpha-lipoic acid; a metabolic antioxidant in
      hypercholesterolemic-induced animals was investigated. Eighteen adult male New
      Zealand White (NZW) rabbit were segregated into three groups labelled as group N,
      HCD and ALA (n = 6). Group N (normal control) was fed with normal chow, the rest
      (HCD and ALA) were fed with 100 g/head/day of 1% cholesterol rich diet to induce
      hypercholesterolemia. Four point two mg/body weight of alpha lipoic acid was
      concomintantly supplemented to the ALA group. Drinking water was given ad
      libitum. The study was designed for 10 weeks. Blood sampling was taken from the
      ear lobe vein at the beginning, week 5 and week 10. Plasma was prepared for lipid
      profile estimation and microsomal lipid peroxidation index indicated with
      malondialdehyde (MDA) formation. At the end of the experiment, the animals were
      sacrificed and the aorta were excised for intimal lesion analysis. The plasma
      total cholesterol (TC) and low density lipoprotein (LDL) levels were found to be
      significantly low in ALA group compared to that of the HCD group (p<0.05).
      Similarly, low level of MDA (p<0.05) in ALA group was observed compared to that
      of the HCD group showing a significant reduction of lipid peroxidation activity.
      Histomorphometric intimal lesion analysis of the aorta showing less of
      atheromatous plaque formation in alpha lipoic acid supplemented group (p<0.05)
      compared to HCD group. These findings suggested that alpha lipoic acid posses a
      dual lipid lowering and anti-atherosclerotic properties indicated with low plasma
      TC and LDL levels and reduction of athero-lesion formation in
      hypercholesterolemic-induced rabbits.

PMID- 18818759
TI  - Coenzyme Q10-Binding/Transfer Protein Saposin B also Binds gamma-Tocopherol.
AB  - gamma-Tocopherol, the major form of dietary vitamin E, is absorbed in the
      intestine and is secreted in chylomicrons, which are then transferred to liver
      lysosomes. Most gamma-tocopherol is transferred to liver microsomes and is
      catabolized by cytochrome p450. Due to the hydrophobicity of gamma-tocopherol, a
      binding and transfer protein is plausible, but none have yet been isolated and
      characterized. We recently found that a ubiquitous cytosolic protein, saposin B,
      binds and transfers coenzyme Q10 (CoQ10), which is an essential factor for ATP
      production and an important antioxidant. Here, we report that saposin B also
      binds gamma-tocopherol, but not alpha-tocopherol, as efficiently as CoQ10 at pH
      7.4. At acidic pH, saposin B binds gamma-tocopherol preferentially to CoQ10 and
      alpha-tocopherol. Furthermore, we confirmed that saposin B selectively binds
      gamma-tocopherol instead of CoQ10 and alpha-tocopherol at every pH between 5.4
      and 8.0 when all three lipids are competing for binding. We detected gamma
      tocopherol in human saposin B monoclonal antibody-induced immunoprecipitates from
      human urine, although the amount of gamma-tocopherol was much smaller than that
      of CoQ10. These results suggest that saposin B binds and transports gamma
      tocopherol in human cells.

PMID- 18818760
TI  - Sex-specific genetic structure and social organization in Central Asia: insights
      from a multi-locus study.
AB  - In the last two decades, mitochondrial DNA (mtDNA) and the non-recombining
      portion of the Y chromosome (NRY) have been extensively used in order to measure
      the maternally and paternally inherited genetic structure of human populations,
      and to infer sex-specific demography and history. Most studies converge towards
      the notion that among populations, women are genetically less structured than
      men. This has been mainly explained by a higher migration rate of women, due to
      patrilocality, a tendency for men to stay in their birthplace while women move to
      their husband's house. Yet, since population differentiation depends upon the
      product of the effective number of individuals within each deme and the migration
      rate among demes, differences in male and female effective numbers and sex-biased
      dispersal have confounding effects on the comparison of genetic structure as
      measured by uniparentally inherited markers. In this study, we develop a new
      multi-locus approach to analyze jointly autosomal and X-linked markers in order
      to aid the understanding of sex-specific contributions to population
      differentiation. We show that in patrilineal herder groups of Central Asia, in
      contrast to bilineal agriculturalists, the effective number of women is higher
      than that of men. We interpret this result, which could not be obtained by the
      analysis of mtDNA and NRY alone, as the consequence of the social organization of
      patrilineal populations, in which genetically related men (but not women) tend to
      cluster together. This study suggests that differences in sex-specific migration
      rates may not be the only cause of contrasting male and female differentiation in
      humans, and that differences in effective numbers do matter.

PMID- 18818761
TI  - Distinct effects of IL-18 on the engraftment and function of human effector CD8 T
      cells and regulatory T cells.
AB  - IL-18 has pleotropic effects on the activation of T cells during antigen
      presentation. We investigated the effects of human IL-18 on the engraftment and
      function of human T cell subsets in xenograft mouse models. IL-18 enhanced the
      engraftment of human CD8(+) effector T cells and promoted the development of
      xenogeneic graft versus host disease (GVHD). In marked contrast, IL-18 had
      reciprocal effects on the engraftment of CD4(+)CD25(+)Foxp3(+) regulatory T cells
      (Tregs) in the xenografted mice. Adoptive transfer experiments indicated that IL
      18 prevented the suppressive effects of Tregs on the development of xenogeneic
      GVHD. The IL-18 results were robust as they were observed in two different mouse
      strains. In addition, the effects of IL-18 were systemic as IL-18 promoted
      engraftment and persistence of human effector T cells and decreased Tregs in
      peripheral blood, peritoneal cavity, spleen and liver. In vitro experiments
      indicated that the expression of the IL-18Ralpha was induced on both CD4 and CD8
      effector T cells and Tregs, and that the duration of expression was less
      sustained on Tregs. These preclinical data suggest that human IL-18 may have use
      as an adjuvant for immune reconstitution after cytotoxic therapies, and to
      augment adoptive immunotherapy, donor leukocyte infusions, and vaccine
      strategies.

PMID- 18818762
TI  - Predicting quantitative genetic interactions by means of sequential matrix
      approximation.
AB  - Despite the emerging experimental techniques for perturbing multiple genes and
      measuring their quantitative phenotypic effects, genetic interactions have
      remained extremely difficult to predict on a large scale. Using a recent high
      resolution screen of genetic interactions in yeast as a case study, we
      investigated whether the extraction of pertinent information encoded in the
      quantitative phenotypic measurements could be improved by computational means. By
      taking advantage of the observation that most gene pairs in the genetic
      interaction screens have no significant interactions with each other, we
      developed a sequential approximation procedure which ranks the mutation pairs in
      order of evidence for a genetic interaction. The sequential approximations can
      efficiently remove background variation in the double-mutation screens and give
      increasingly accurate estimates of the single-mutant fitness measurements.
      Interestingly, these estimates not only provide predictions for genetic
      interactions which are consistent with those obtained using the measured fitness,
      but they can even significantly improve the accuracy with which one can
      distinguish functionally-related gene pairs from the non-interacting pairs. The
      computational approach, in general, enables an efficient exploration and
      classification of genetic interactions in other studies and systems as well.

PMID- 18818763
TI  - Research ethics training in Peru: a case study.
AB  - With the rapidly increasing number of health care professionals seeking
      international research experience, comes an urgent need for enhanced capacity of
      host country institutional review boards (IRB) to review research proposals and
      ensure research activities are both ethical and relevant to the host country
      customs and needs. A successful combination of distance learning, interactive
      courses and expert course instructors has been applied in Peru since 2004 through
      collaborations between the U.S. Naval Medical Research Center Detachment, the
      University of Washington and the Department of Clinical Bioethics of the National
      Institutes of Health to provide training in ethical conduct of research to IRB
      members and researchers from Peru and other Latin American countries. All
      training activities were conducted under the auspices of the Peruvian National
      Institute of Health (INS), Ministry of Health. To date, 927 people from 12
      different Latin American countries have participated in several of these training
      activities. In this article we describe our training model.

PMID- 18818764
TI  - Tracing the source of campylobacteriosis.
AB  - Campylobacter jejuni is the leading cause of bacterial gastro-enteritis in the
      developed world. It is thought to infect 2-3 million people a year in the US
      alone, at a cost to the economy in excess of US $4 billion. C. jejuni is a
      widespread zoonotic pathogen that is carried by animals farmed for meat and
      poultry. A connection with contaminated food is recognized, but C. jejuni is also
      commonly found in wild animals and water sources. Phylogenetic studies have
      suggested that genotypes pathogenic to humans bear greatest resemblance to non
      livestock isolates. Moreover, seasonal variation in campylobacteriosis bears the
      hallmarks of water-borne disease, and certain outbreaks have been attributed to
      contamination of drinking water. As a result, the relative importance of these
      reservoirs to human disease is controversial. We use multilocus sequence typing
      to genotype 1,231 cases of C. jejuni isolated from patients in Lancashire,
      England. By modeling the DNA sequence evolution and zoonotic transmission of C.
      jejuni between host species and the environment, we assign human cases
      probabilistically to source populations. Our novel population genetics approach
      reveals that the vast majority (97%) of sporadic disease can be attributed to
      animals farmed for meat and poultry. Chicken and cattle are the principal sources
      of C. jejuni pathogenic to humans, whereas wild animal and environmental sources
      are responsible for just 3% of disease. Our results imply that the primary
      transmission route is through the food chain, and suggest that incidence could be
      dramatically reduced by enhanced on-farm biosecurity or preventing food-borne
      transmission.

PMID- 18818765
TI  - Sex-biased evolutionary forces shape genomic patterns of human diversity.
AB  - Comparisons of levels of variability on the autosomes and X chromosome can be
      used to test hypotheses about factors influencing patterns of genomic variation.
      While a tremendous amount of nucleotide sequence data from across the genome is
      now available for multiple human populations, there has been no systematic effort
      to examine relative levels of neutral polymorphism on the X chromosome versus
      autosomes. We analyzed approximately 210 kb of DNA sequencing data representing
      40 independent noncoding regions on the autosomes and X chromosome from each of
      90 humans from six geographically diverse populations. We correct for differences
      in mutation rates between males and females by considering the ratio of within
      human diversity to human-orangutan divergence. We find that relative levels of
      genetic variation are higher than expected on the X chromosome in all six human
      populations. We test a number of alternative hypotheses to explain the excess
      polymorphism on the X chromosome, including models of background selection,
      changes in population size, and sex-specific migration in a structured
      population. While each of these processes may have a small effect on the relative
      ratio of X-linked to autosomal diversity, our results point to a systematic
      difference between the sexes in the variance in reproductive success; namely, the
      widespread effects of polygyny in human populations. We conclude that factors
      leading to a lower male versus female effective population size must be
      considered as important demographic variables in efforts to construct models of
      human demographic history and for understanding the forces shaping patterns of
      human genomic variability.

PMID- 18818766
TI  - Successful inhibition of tumor development by specific class-3 semaphorins is
      associated with expression of appropriate semaphorin receptors by tumor cells.
AB  - The class-3 semaphorins (sema3s) include seven family members. Six of them bind
      to neuropilin-1 (np1) or neuropilin-2 (np2) receptors or to both, while the
      seventh, sema3E, binds to the plexin-D1 receptor. Sema3B and sema3F were
      previously characterized as tumor suppressors and as inhibitors of tumor
      angiogenesis. To determine if additional class-3 semaphorins such as sema3A,
      sema3D, sema3E and sema3G possess anti-angiogenic and anti-tumorigenic
      properties, we expressed the recombinant full length semaphorins in four
      different tumorigenic cell lines expressing different combinations of class-3
      semaphorin receptors. We show for the first time that sema3A, sema3D, sema3E and
      sema3G can function as potent anti-tumorigenic agents. All the semaphorins we
      examined were also able to reduce the concentration of tumor associated blood
      vessels although the potencies of the anti-angiogenic effects varied depending on
      the tumor cell type. Surprisingly, there was little correlation between the
      ability to inhibit tumor angiogenesis and their anti-tumorigenic activity. None
      of the semaphorins inhibited the adhesion of the tumor cells to plastic or
      fibronectin nor did they modulate the proliferation of tumor cells cultured in
      cell culture dishes. However, various semaphorins were able to inhibit the
      formation of soft agar colonies from tumor cells expressing appropriate
      semaphorin receptors, although in this case too the inhibitory effect was not
      always correlated with the anti-tumorigenic effect. In contrast, the anti
      tumorigenic effect of each of the semaphorins correlated very well with tumor
      cell expression of specific signal transducing receptors for particular
      semaphorins. This correlation was not broken even in cases in which the tumor
      cells expressed significant concentrations of endogenous semaphorins. Our results
      suggest that combinations of different class-3 semaphorins may be more effective
      than single semaphorins in cases in which tumor cells express more than one type
      of semaphorin receptors.

PMID- 18818767
TI  - Recruitment of activation receptors at inhibitory NK cell immune synapses.
AB  - Natural killer (NK) cell activation receptors accumulate by an actin-dependent
      process at cytotoxic immune synapses where they provide synergistic signals that
      trigger NK cell effector functions. In contrast, NK cell inhibitory receptors,
      including members of the MHC class I-specific killer cell Ig-like receptor (KIR)
      family, accumulate at inhibitory immune synapses, block actin dynamics, and
      prevent actin-dependent phosphorylation of activation receptors. Therefore, one
      would predict inhibition of actin-dependent accumulation of activation receptors
      when inhibitory receptors are engaged. By confocal imaging of primary human NK
      cells in contact with target cells expressing physiological ligands of NK cell
      receptors, we show here that this prediction is incorrect. Target cells included
      a human cell line and transfected Drosophila insect cells that expressed ligands
      of NK cell activation receptors in combination with an MHC class I ligand of
      inhibitory KIR. The two NK cell activation receptors CD2 and 2B4 accumulated and
      co-localized with KIR at inhibitory immune synapses. In fact, KIR promoted CD2
      and 2B4 clustering, as CD2 and 2B4 accumulated more efficiently at inhibitory
      synapses. In contrast, accumulation of KIR and of activation receptors at
      inhibitory synapses correlated with reduced density of the integrin LFA-1. These
      results imply that inhibitory KIR does not prevent CD2 and 2B4 signaling by
      blocking their accumulation at NK cell immune synapses, but by blocking their
      ability to signal within inhibitory synapses.

PMID- 18818768
TI  - Unphosphorylated SR-like protein Npl3 stimulates RNA polymerase II elongation.
AB  - The production of a functional mRNA is regulated at every step of transcription.
      An area not well-understood is the transition of RNA polymerase II from
      elongation to termination. The S. cerevisiae SR-like protein Npl3 functions to
      negatively regulate transcription termination by antagonizing the binding of
      polyA/termination proteins to the mRNA. In this study, Npl3 is shown to interact
      with the CTD and have a direct stimulatory effect on the elongation activity of
      the polymerase. The interaction is inhibited by phosphorylation of Npl3. In
      addition, Casein Kinase 2 was found to be required for the phosphorylation of
      Npl3 and affect its ability to compete against Rna15 (Cleavage Factor I) for
      binding to polyA signals. Our results suggest that phosphorylation of Npl3
      promotes its dissociation from the mRNA/RNAP II, and contributes to the
      association of the polyA/termination factor Rna15. This work defines a novel role
      for Npl3 in elongation and its regulation by phosphorylation.

PMID- 18818769
TI  - Organization of excitable dynamics in hierarchical biological networks.
AB  - This study investigates the contributions of network topology features to the
      dynamic behavior of hierarchically organized excitable networks. Representatives
      of different types of hierarchical networks as well as two biological neural
      networks are explored with a three-state model of node activation for
      systematically varying levels of random background network stimulation. The
      results demonstrate that two principal topological aspects of hierarchical
      networks, node centrality and network modularity, correlate with the network
      activity patterns at different levels of spontaneous network activation. The
      approach also shows that the dynamic behavior of the cerebral cortical systems
      network in the cat is dominated by the network's modular organization, while the
      activation behavior of the cellular neuronal network of Caenorhabditis elegans is
      strongly influenced by hub nodes. These findings indicate the interaction of
      multiple topological features and dynamic states in the function of complex
      biological networks.

PMID- 18818770
TI  - Wolbachia mediate variation of host immunocompetence.
AB  - BACKGROUND: After decades during which endosymbionts were considered as silent in
      their hosts, in particular concerning the immune system, recent studies have
      revealed the contrary. In the present paper, we addressed the effect of
      Wolbachia, the most prevalent endosymbiont in arthropods, on host
      immunocompetence. To this end, we chose the A. vulgare-Wolbachia symbiosis as a
      model system because it leads to compare consequences of two Wolbachia strains
      (wVulC and wVulM) on hosts from the same population. Moreover, A. vulgare is the
      only host-species in which Wolbachia have been directly observed within
      haemocytes which are responsible for both humoral and cellular immune responses.
      METHODOLOGY/PRINCIPAL FINDINGS: We sampled gravid females from the same
      population that were either asymbiotic, infected with wVulC, or infected with
      wVulM. The offspring from these females were tested and it was revealed that
      individuals harbouring wVulC exhibited: (i) lower haemocyte densities, (ii) more
      intense septicaemia in their haemolymph and (iii) a reduced lifespan as compared
      to individuals habouring wVulM or asymbiotic ones. Therefore, individuals in this
      population of A. vulgare appeared to suffer more from wVulC than from wVulM.
      Symbiotic titer and location in the haemocytes did not differ for the two
      Wolbachia strains showing that these two parameters were not responsible for
      differences observed in their extended phenotypes in A. vulgare.
      CONCLUSION/SIGNIFICANCE: The two Wolbachia strains infecting A. vulgare in the
      same population induced variation in immunocompetence and survival of their
      hosts. Such variation should highly influence the dynamics of this host-symbiont
      system. We propose in accordance with previous population genetic works, that
      wVulM is a local strain that has attenuated its virulence through a long term
      adaptation process towards local A. vulgare genotypes whereas wVulC, which is a
      widespread and invasive strain, is not locally adapted.

PMID- 18818771
TI  - SLEPR: a sample-level enrichment-based pathway ranking method -- seeking
      biological themes through pathway-level consistency.
AB  - Analysis of microarray and other high throughput data often involves
      identification of genes consistently up or down-regulated across samples as the
      first step in extraction of biological meaning. This gene-level paradigm can be
      limited as a result of valid sample fluctuations and biological complexities. In
      this report, we describe a novel method, SLEPR, which eliminates this limitation
      by relying on pathway-level consistencies. Our method first selects the sample
      level differentiated genes from each individual sample, capturing genes missed by
      other analysis methods, ascertains the enrichment levels of associated pathways
      from each of those lists, and then ranks annotated pathways based on the
      consistency of enrichment levels of individual samples from both sample classes.
      As a proof of concept, we have used this method to analyze three public
      microarray datasets with a direct comparison with the GSEA method, one of the
      most popular pathway-level analysis methods in the field. We found that our
      method was able to reproduce the earlier observations with significant
      improvements in depth of coverage for validated or expected biological themes,
      but also produced additional insights that make biological sense. This new method
      extends existing analyses approaches and facilitates integration of different
      types of HTP data.

PMID- 18818772
TI  - Neural correlate of filtering of irrelevant information from visual working
      memory.
AB  - In a dynamic environment stimulus task relevancy could be altered through time
      and it is not always possible to dissociate relevant and irrelevant objects from
      the very first moment they come to our sight. In such conditions, subjects need
      to retain maximum possible information in their WM until it is clear which items
      should be eliminated from WM to free attention and memory resources. Here, we
      examined the neural basis of irrelevant information filtering from WM by
      recording human ERP during a visual change detection task in which the stimulus
      irrelevancy was revealed in a later stage of the task forcing the subjects to
      keep all of the information in WM until test object set was presented. Assessing
      subjects' behaviour we found that subjects' RT was highly correlated with the
      number of irrelevant objects and not the relevant one, pointing to the notion
      that filtering, and not selection, process was used to handle the distracting
      effect of irrelevant objects. In addition we found that frontal N150 and parietal
      N200 peak latencies increased systematically as the amount of irrelevancy load
      increased. Interestingly, the peak latency of parietal N200, and not frontal
      N150, better correlated with subjects' RT. The difference between frontal N150
      and parietal N200 peak latencies varied with the amount of irrelevancy load
      suggesting that functional connectivity between modules underlying fronto
      parietal potentials vary concomitant with the irrelevancy load. These findings
      suggest the existence of two neural modules, responsible for irrelevant objects
      elimination, whose activity latency and functional connectivity depend on the
      number of irrelevant object.

PMID- 18818773
TI  - Analysis of HIV Protease Killing Through Caspase 8 Reveals a Novel Interaction
      Between Caspase 8 and Mitochondria.
AB  - Human Immunodeficiency Virus (HIV) protease initiates apoptosis of HIV-infected
      cells by proteolytic cleavage of procaspase 8, creating a novel peptide termed
      casp8p41. Expression of casp8p41 alone is sufficient to initiate caspase
      dependent cell death associated with mitochondrial depolarization. Since casp8p41
      does not contain the catalytic cysteine at position 360, the mechanism by which
      casp8p41 initiates apoptosis is unclear. We demonstrate that casp8p41 directly
      causes mitochondrial depolarization and release of cytochrome c with downstream
      caspase 9 activation. Moreover, death induced by casp8p41 requires the presence
      of mitochondria, and in intact cells, casp8p41 colocalizes with mitochondria.
      These results illuminate a novel mechanism of cell death induced by a caspase 8
      cleavage fragment whereby mitochondrial interaction leads to depolarization and
      cytochrome c release.

PMID- 18818774
TI  - HIV Protease Cleavage of Procaspase 8 is Necessary for Death of HIV-Infected
      Cells.
AB  - Numerous host and viral factors are capable of causing death of HIV infected
      cells, uninfected bystander cells, or both. We assessed the relevance of HIV
      protease in infected cell killing by mutating its obligate substrate for death,
      procaspase 8. VSV pseudotyped HIV infection of cells expressing WT caspase 8
      resulted in apoptotic cell death and generation of the HIV protease specific
      cleavage product of procaspase 8, casp8p41. Conversely, both cell death and
      casp8p41 production were inhibited in cells expressing procaspase 8 engineered to
      be resistant to HIV protease cleavage. Lymph nodes from HIV-infected patients
      with ongoing viral replication also selectively expressed casp8p41, which
      colocalized with both infected and apoptotic cells. HIV protease cleavage of
      procaspase 8 appears to be a necessary event for infected cell killing, which is
      responsible for infected cell death within lymphoid tissues from HIV-infected
      patients.

PMID- 18818775
TI  - The role of obstetrician/gynecologists in the management of hepatitis C virus
      infection.
AB  - Chronic infection with hepatitis C virus (HCV) is a major cause of liver disease
      related death and is also the most frequent indication for liver transplantation
      in USA. Infected individuals can remain asymptomatic for 20 years or more, but
      they remain at risk for progressive liver disease. They also represent a
      potential source of infection for others. For reducing the future disease burden
      due to HCV, obstetrician/gynecologists and primary health care practitioners
      should be aware of the factors that promote HCV transmission: how to provide
      counseling and testing, and when specialist referral is needed.

PMID- 18818776
TI  - PPNEMA: A resource of plant-parasitic nematodes multialigned ribosomal cistrons.
AB  - Plant-parasitic nematodes are important pests of crop plants worldwide, and also
      among the most difficult animals to identify. Their identification based on
      nuclear ribosomal DNA (rDNA) cistron (18S, 28S, and 5.8S RNA genes, and internal
      transcribed spacers, ITS1 and ITS2) is becoming a popular tool. Sequences from
      nuclear ribosomal RNA repeats have been used to demonstrate the identity of
      isolates from various hosts and to unravel the relationships of cryptic and
      complex species. In addition, the availability of RNA sequences allows study of
      phylogenetic relationships between nematodes, also for more complete
      understanding of their biology as agricultural pests. PPNEMA is a plant-parasitic
      nematode bioinformatic resource. It consists of a database of ribosomal cistron
      sequences from various species grouped according to nematode genera, and a search
      system allowing data to be extracted according to both text and pattern
      searching. PPNEMA offers to the scientific community a preprocessed archive of
      plant parasitic nematode sequences useful for nematologists. It is a tool to
      retrieve plant nematode multialigned sequences for phylogenetic studies or to
      recognize a nematode by comparing its rDNA sequence with the PPNEMA available
      genus specific multialignments.

PMID- 18818777
TI  - Abstracts of the Canadian Surgery Forum 2008. September 11-14, 2008. Halifax,
      Nova Scotia, Canada.

PMID- 18818781
TI  - Remember to use our chronic obstructive pulmonary disease action plan.

PMID- 18818782
TI  - Sex disparities in effects of cystic fibrosis-related diabetes on clinical
      outcomes: a matched study.
AB  - BACKGROUND: Cystic fibrosis-related diabetes (CFRD) is an increasingly prevalent
      comorbidity factor for patients with cystic fibrosis (CF). CFRD has been
      associated with an accelerated decline in clinical parameters and an increased
      mortality rate. OBJECTIVES: To investigate the clinical impact of CFRD on
      pulmonary function and clinical status using a matched study design to further
      explore potential causality. METHODS: Charts from the adult CF clinic at St
      Paul's Hospital (Vancouver, British Columbia) were retrospectively reviewed.
      Forty CFRD patients with and without fasting hyperglycemia were matched to CF
      patients with nondiabetic glucose tolerance based on sex, age and forced
      expiratory volume in 1 s (FEV(1)). RESULTS: Sixteen of 40 CFRD patients (40%)
      died compared with nine of 40 patient controls (23%) (P=0.13). CFRD patients were
      more likely to experience declines in FEV(1) (P<0.01), especially women (P<0.01).
      Patients with CFRD were not more likely to be hospitalized (P=0.39). Body mass
      index did not differ between groups. CONCLUSIONS: Patients with CFRD had higher
      rates of FEV(1) deterioration than nondiabetic patients with CF, and showed a
      trend toward increased mortality. The present study suggests that CFRD has a
      significant clinical impact and should be carefully considered when evaluating
      the status of CF patients.

PMID- 18818783
TI  - Comparison of Canadian versus United States emergency department visits for
      chronic obstructive pulmonary disease exacerbation.
AB  - INTRODUCTION: Despite the frequency of emergency department (ED) visits for
      chronic obstructive pulmonary disease (COPD) exacerbation, little is known about
      practice variation in EDs. OBJECTIVES: To examine the differences between
      Canadian and United States (US) COPD patients, and the ED management they
      receive. METHODS: A prospective multicentre cohort study was conducted involving
      29 EDs in the US and Canada. Using a standard protocol, consecutive ED patients
      with COPD exacerbations were interviewed, their charts reviewed and a two-week
      telephone follow-up completed. Comparisons between Canadian and US patients, as
      well as their treatment and outcomes, were made. Predictors of antibiotic use
      were determined by multivariate logistic regression. RESULTS: Of 584 patients who
      had physician-diagnosed COPD, 397 (68%) were enrolled. Of these, 63 patients
      (16%) were from Canada. Canadians were older (73 years versus 69 years; P=0.002),
      more often white (97% versus 65%; P<0.001), less educated (P=0.003) and more
      commonly insured (P<0.001) than the US patients. US patients more commonly used
      the ED for their usual COPD medications (17% versus 3%; P=0.005). Although
      Canadian patients had fewer pack-years of smoking (45 pack-years versus 53 pack
      years; P=0.001), current COPD medications and comorbidities were similar. At ED
      presentation, Canadian patients were more often hypoxic and symptomatic. ED
      treatment with inhaled beta-agonists (approximately 90%) and systemic
      corticosteroids (approximately 65%) were similar; Canadians received more
      antibiotics (46% versus 25%; P<0.001) and other treatments (29% versus 11%;
      P=0.002). Admission rates were similar in both countries (approximately 65%),
      although Canadian patients remained in the ED longer than the US patients (10 h
      versus 5 h, respectively; P<0.001). CONCLUSIONS: Overall, patients with acute
      COPD in Canada and the US appear to have similar history, ED treatment and
      outcomes; however, Canadian patients are older and receive more aggressive
      treatment in the ED. In both countries, the prolonged length of stay and high
      admission rate contribute to the ED overcrowding crisis facing EDs.

PMID- 18818784
TI  - Towards Excellence in Asthma Management: final report of an eight-year program
      aimed at reducing care gaps in asthma management in Quebec.
AB  - BACKGROUND AND OBJECTIVES: Asthma care in Canada and around the world
      persistently falls short of optimal treatment. To optimize care, a systematic
      approach to identifying such shortfalls or 'care gaps', in which all stakeholders
      of the health care system (including patients) are involved, was proposed.
      METHODS: Several projects of a multipartner, multidisciplinary disease management
      program, developed to optimize asthma care in Quebec, was conducted in a period
      of eight years. First, two population maps were produced to identify regional
      variations in asthma-related morbidity and to prioritize interventions for
      improving treatment. Second, current care was evaluated in a physician-patient
      cohort, confirming the many care gaps in asthma management. Third, two series of
      peer-reviewed outcome studies, targeting high-risk populations and specific
      asthma care gaps, were conducted. Finally, a process to integrate the best
      interventions into the health care system and an agenda for further research on
      optimal asthma management were proposed. RESULTS: Key observations from these
      studies included the identification of specific patterns of noncompliance in
      using inhaled corticosteroids, the failure of increased access to spirometry in
      asthma education centres to increase the number of education referrals, the
      transient improvement in educational abilities of nurses involved with an asthma
      hotline telephone service, and the beneficial effects of practice tools aimed at
      facilitating the assessment of asthma control and treatment needs by general
      practitioners. CONCLUSIONS: Disease management programs such as Towards
      Excellence in Asthma Management can provide valuable information on optimal
      strategies for improving treatment of asthma and other chronic diseases by
      identifying care gaps, improving guidelines implementation and optimizing care.

PMID- 18818785
TI  - Nitrofurantoin-associated bronchiolitis obliterans organizing pneumonia: report
      of a case.
AB  - Bronchiolitis obliterans organizing pneumonia due to nitrofurantoin has rarely
      been reported and is associated with poor outcomes. A case of nitrofurantoin
      associated bronchiolitis obliterans organizing pneumonia responsive to drug
      withdrawal and corticosteroids is presented.

PMID- 18818787
TI  - Endoscopic band ligation for nonvariceal bleeding: a review.

PMID- 18818788
TI  - Comparison of liver biopsy and transient elastography based on clinical
      relevance.
AB  - BACKGROUND: Liver stiffness measurement (LSM) by transient elastography has
      recently been validated for the evaluation of liver fibrosis in chronic liver
      diseases. The present study focused on cases in which liver biopsy and LSM were
      discordant. METHODS: Three hundred eighty-six patients with chronic hepatitis C
      who underwent a liver biopsy between December 2004 and April 2007 were studied.
      First, the optimal cut-off value of LSM was selected for the determination of
      cirrhosis based on the receiver operating characteristic curve. Then, the cases
      in which liver histology and evaluation by LSM were discordant were selected.
      Laboratory test results such as serum total bilirubin concentration, prothrombin
      activity, albumin concentration, platelet count and the aspartate
      aminotransferase to platelet ratio index, together with the presence of
      esophageal varices, were analyzed. RESULTS: The optimal cut-off value was chosen
      to be 15.9 kPa for cirrhosis (fibrosis stage [F] 4) determination to maximize the
      sum of sensitivity (78.9%) and specificity (81.0%). There were 78 discordant
      cases: 51 patients showed an LSM of 15.9 kPa or higher and a fibrosis stage of F1
      to F3 (high LSM group), and 27 patients had an LSM lower than 15.9 kPa and a
      fibrosis stage of F4 (low LSM group). Esophageal varices were seen in 11 patients
      in the high LSM group (n=51) and in no patients in the low LSM group (n=27)
      (P=0.0012). The aspartate aminotransferase to platelet ratio index was
      significantly higher in the high LSM group (1.49 versus 0.89, P=0.019). Other
      parameters did not differ significantly. However, platelet count, prothrombin
      activity and albumin concentration tended to be lower in the high LSM group.
      CONCLUSIONS: Patients with a high LSM need proper attention for cirrhosis, even
      if liver biopsy does not reveal cirrhosis.

PMID- 18818789
TI  - Incidental colorectal computed tomography abnormalities: would you send every
      patient for a colonoscopy?
AB  - BACKGROUND: The clinical significance of colorectal wall thickening (CRWT) in
      patients undergoing abdominal computed tomography (CT) has not yet been
      definitively established. OBJECTIVES: To compare alleged findings on abdominal CT
      with those of a follow-up colonoscopy. METHODS: Ninety-four consecutive patients
      found to have large-bowel abnormalities on abdominal CT were referred for
      colonoscopy. Of these patients, 48 were referred for a suspected colorectal
      tumour and 46 for CRWT. Colonoscopy was performed and findings were compared.
      RESULTS: Of the 48 suspected colorectal tumours, 34 were determined to be
      neoplastic lesions on colonoscopy. Of these, 26 were malignant and eight were
      benign. Colonoscopy revealed no abnormality in 30 of 46 patients with CRWT as a
      solitary finding, and revealed some abnormality in 16 patients (12 had
      diverticular disease, four had benign neoplastic lesions). CONCLUSIONS: CRWT as
      an incidental and solitary finding on CT should not be regarded as a pathology
      prompting a colonoscopy. Approximately two-thirds of the patients had a normal
      colonoscopy and the remaining patients had benign lesions (12 had diverticular
      disease and four had benign neoplastic lesions). However, many of these patients
      seem to warrant colonoscopy regardless of CT findings, particularly patients who
      have a family history of colorectal cancer, have positive fecal occult blood test
      results or who are older than 50 years of age.

PMID- 18818790
TI  - Association between proton pump inhibitors and respiratory infections: a
      systematic review and meta-analysis of clinical trials.
AB  - BACKGROUND: Proton pump inhibitors (PPIs) have become the mainstay of treatment
      for and prevention of many serious gastrointestinal diseases. Laboratory and
      clinical evidence suggests that the increase in gastric pH caused by PPIs may be
      linked to increased bacterial colonization of the stomach and may predispose
      patients to an increased risk for respiratory infections. OBJECTIVE: To examine
      the association between PPI treatment and respiratory infections. METHODS: A
      literature search was conducted using PubMed, MEDLINE and Cochrane databases of
      randomized, placebo-controlled trials evaluating the efficacy of PPIs. Studies
      that listed and quantified the specific adverse events of 'respiratory infection'
      or 'upper respiratory infection' (or equivalent), and compared their rates
      between PPIs and placebo were included. The chi(2) analysis was used to calculate
      the significance of association in individual studies and a meta-analysis of the
      selected studies was performed. RESULTS: Of 7457 studies initially identified and
      70 relevant randomized, controlled trials (RCTs) selected, seven studies met the
      inclusion criteria. A total of 16 comparisons for chi(2) analysis were possible
      given the multiple dosage arms used in several studies. PPIs included in the
      studies were esomeprazole, rabeprazole, pantoprazole and omeprazole. More than
      one-half of the studies showed a trend toward an association between PPI use and
      respiratory infections, although the majority of the studies failed to show a
      significant correlation. A single study using high-dose esomeprazole (40 mg)
      showed a significant association -4.3% rate of respiratory infections in the
      active group compared with 0% in the placebo group (P<0.05). Meta-analysis showed
      a trend toward an association between PPIs and respiratory infections, although
      it failed to reach significance (OR 1.42, 95% CI 0.86 to 2.35; P=0.17).
      CONCLUSION: Although a trend was evident in both a chi(2) analysis of individual
      studies and a meta-analysis, the present review and meta-analysis failed to show
      a conclusive association between PPIs and respiratory infections. Very few RCTs
      actively sought out respiratory infections, which excluded the majority of RCTs
      identified. A well-structured, placebo-controlled prospective study would be
      needed to determine whether a true association between PPIs and respiratory
      infections exists.

PMID- 18818791
TI  - Procedural skills education--colonoscopy as a model.
AB  - Traditionally, surgical and procedural apprenticeship has been an assumed
      activity of students, without a formal educational context. With increasing
      barriers to patient and operating room access such as shorter work week hours for
      residents, and operating room and endoscopy time at a premium, alternate
      strategies to maximizing procedural skill development are being considered.
      Recently, the traditional surgical apprenticeship model has been challenged, with
      greater emphasis on the need for surgical and procedural skills training to be
      more transparent and for alternatives to patient-based training to be considered.
      Colonoscopy performance is a complex psychomotor skill requiring practitioners to
      integrate multiple sensory inputs, and involves higher cortical centres for
      optimal performance. Colonoscopy skills involve mastery in the cognitive,
      technical and process domains. In the present review, we propose a model for
      teaching colonoscopy to the novice trainee based on educational theory.

PMID- 18818792
TI  - Latent lymphocytic enterocolitis associated with celiac disease manifesting after
      resection for colon cancer: case report and review of the literature.
AB  - Lymphocytic colitis, a cause of chronic watery diarrhea, is histologically
      characterized by increased intraepithelial lymphocytosis. Studies have associated
      this disorder with celiac disease, although there are no reports of patients with
      both lymphocytic colitis and colon cancer. The present case report describes a
      patient with lymphocytic colitis, which manifested five years after he presented
      with a cecal adenocarcinoma, and three years following a diagnosis of celiac
      disease. Pathological review of his initial resection specimen demonstrated
      lymphocytic enterocolitis, indicating a five-year latency in the presentation of
      this disease.

PMID- 18818794
TI  - Simulation tools for lab on a chip research: advantages, challenges, and thoughts
      for the future.

PMID- 18818795
TI  - Droplet-based microfluidic system for individual Caenorhabditis elegans assay.
AB  - A droplet-based microfluidic system integrating a droplet generator and a droplet
      trap array is described for encapsulating individual Caenorhabditis elegans into
      a parallel series of droplets, enabling characterization of the worm behavior in
      response to neurotoxin at single-animal resolution.

PMID- 18818796
TI  - Millisecond denaturation dynamics of fluorescent proteins revealed by femtoliter
      container on micro-thermodevice.
AB  - Real-time observation of biomolecular behavior focusing on high speed temperature
      response is an essential endeavor for further biological study at the molecular
      level. This is because most of the important biological functions at the
      molecular level happen at the sub-second time scale. We used our own on-chip
      microheaters and microcontainers to observe the denaturation dynamics of
      fluorescent proteins at the millisecond time scale. The microheater controls the
      temperature in 1 ms under the microscope. Fluorescent proteins were contained in
      28 fL PDMS microcontainers to prevent them from diffusing into the solution. The
      proteins were denatured by high temperatures and observed by a high speed CCD
      camera with 5 ms per frame. Hence, denaturation speeds of red fluorescent
      proteins (rDsRed and rHcRed) were measured to be 5-10 ms. Green fluorescent
      proteins (rAcGFP and rGFPuv) denatured with bi-exponential decay. rAcGFP
      denatured with time constants of 5 ms and 75 ms while rGFPuv denatured with 10 ms
      and 130 ms. This may be the reverse process of a two step renaturation of GFP
      observed in a previous report. This micro-thermodevice is applicable to other
      biomaterials such as nucleic acids or other proteins. It does not require any
      chemical treatment nor mutation to the biomaterial itself. Therefore, the
      methodology using this general purpose device gives access to biomolecular
      studies in short time scales and acts as a powerful tool in molecular biology.

PMID- 18818797
TI  - Setting up roadblocks for kinesin-1: mechanism for the selective speed control of
      cargo carrying microtubules.
AB  - Motor-driven cytoskeletal filaments are versatile transport platforms for
      nanosized cargo in molecular sorting and nano-assembly devices. However, because
      cargo and motors share the filament lattice as a common substrate for their
      activity, it is important to understand the influence of cargo-loading on
      transport properties. By performing single-molecule stepping assays on
      biotinylated microtubules we found that individual kinesin-1 motors frequently
      stopped upon encounters with attached streptavidin molecules. Consequently, we
      attribute the deceleration of cargo-laden microtubules in gliding assays to an
      obstruction of kinesin-1 paths on the microtubule lattice rather than to
      'frictional' cargo-surface interactions. We propose to apply this obstacle-caused
      slow-down of gliding microtubules in a novel molecular detection scheme: Using a
      mixture of two distinct microtubule populations that each bind a different kind
      of protein, the presence of these proteins can be detected via speed changes in
      the respective microtubule populations.

PMID- 18818798
TI  - Crossing microfluidic streamlines to lyse, label and wash cells.
AB  - We present a versatile method for continuous-flow, on-chip biological processing
      of cells, large bio-particles, and functional beads. Using an asymmetric post
      array in pressure-driven microfluidic flow, we can move particles of interest
      across multiple, independent chemical streams, enabling sequential chemical
      operations. With this method, we demonstrate on-chip cell treatments such as
      labeling and washing, and bacterial lysis and chromosomal extraction. The washing
      capabilities of this method are particularly valuable because they allow many
      analytical or treatment procedures to be cascaded on a single device while still
      effectively isolating their reagents from cross-contamination.

PMID- 18818799
TI  - Novel inorganic polymer derived microreactors for organic microchemistry
      applications.
AB  - Microreactors fabricated with optically transparent inorganic polymers from two
      types of precursors using a UV-microimprinting process demonstrated reliable
      solvent resistance and capability for performing three model organic synthetic
      reactions, which were compared with batch systems and glass based microreactors.

PMID- 18818800
TI  - Open micro-fluidic system for atomic force microscopy-guided in situ
      electrochemical probing of a single cell.
AB  - Ultra-sharp nano-probes and customized atomic force microscopy (AFM) have
      previously been developed in our laboratory for in situ sub-cellular probing of
      electrochemical phenomena in living plant cells during their photosynthesis.
      However, this AFM-based electrochemical probing still has numerous engineering
      challenges such as immobilization of the live cells, compatibility of the
      immobilization procedure with AFM manipulation of the probe, maintenance of
      biological activity of the cells for an extended time while performing the
      measurements, and minimization of electrochemical noise. Thus, we have developed
      an open micro-fluidic channel system (OMFC) in which individual cells can be
      immobilized in micro-traps by capillary flow. This system affords easy AFM access
      and allows for maintenance of the cells in a well-defined chemical environment,
      which sustains their biological activity. The use of micro-channels for making
      the electrochemical measurements significantly reduces parasitic electrical
      capacitances and allows for current detection in the sub-pico-ampere range at
      high signal bandwidths. The OMFC was further studied using simulation packages
      for optimal design conditions. This system was successfully used to measure light
      dependent oxidation currents of a few pico-amperes from the green alga
      Chlamydomonas reinhardtii.

PMID- 18818801
TI  - Design, fabrication and implementation of a novel multi-parameter control
      microfluidic platform for three-dimensional cell culture and real-time imaging.
AB  - New and more biologically relevant in vitro models are needed for use in drug
      development, regenerative medicine, and fundamental scientific investigation.
      While the importance of the extracellular microenvironment is clear, the ability
      to investigate the effects of physiologically relevant biophysical and
      biochemical factors is restricted in traditional cell culture platforms.
      Moreover, the versatility for multi-parameter manipulation, on a single platform,
      with the optical resolution to monitor the dynamics of individual cells or small
      population is lacking. Here we introduce a microfluidic platform for 3D cell
      culture in biologically derived or synthetic hydrogels with the capability to
      monitor cellular dynamics in response to changes in their microenvironment.
      Direct scaffold microinjection, was employed to incorporate 3D matrices into
      microfluidic devices. Our system geometry permits a unique window for studying
      directional migration, e.g. sprouting angiogenesis, since sprouts grow
      predominantly in the microscopic viewing plane. In this study, we demonstrate the
      ability to generate gradients (non-reactive solute), surface shear, interstitial
      flow, and image cells in situ. Three different capillary morphogenesis assays are
      demonstrated. Human adult dermal microvascular endothelial cells (HMVEC-ad) were
      maintained in culture for up to 7 days during which they formed open lumen-like
      structures which was confirmed with confocal microscopy and by perfusion with
      fluorescent microspheres. In the sprouting assay, time-lapse movies revealed
      cellular mechanisms and dynamics (filopodial projection/retraction, directional
      migration, cell division and lumen formation) during tip-cell invasion of
      underlying 3D matrix and subsequent lumen formation.

PMID- 18818802
TI  - Cell characterization using a protein-functionalized pore.
AB  - We demonstrate a highly-sensitive and label-free method for characterizing cells
      based on cell-surface receptors. The method involves measuring a current pulse
      generated when an individual cell passes through an artificial pore. When the
      pore is functionalized with proteins, specific interactions between a cell
      surface marker and the functionalized proteins retard the cell, thus leading to
      an increased pulse duration that indicates the presence of that specific
      biomarker. For proof-of-principle, we successfully screened murine
      erythroleukemia cells based on their CD34 surface marker in both a single and
      mixed population of cells. Further, we developed a unified constrained
      statistical model for estimating the ratios of cells in a mixed population.
      Finally, we demonstrated our ability to screen a small number of cells (hundreds
      or less) with high accuracy and sensitivity. Overall, our pore-based method is
      broadly applicable and, in the future, could provide a full range of in vitro
      cell-based assays.

PMID- 18818803
TI  - Microfluidic devices for studies of shear-dependent platelet adhesion.
AB  - Adhesion of platelets to blood vessel walls is a shear stress dependent process
      that promotes arrest of bleeding and is mediated by the interaction of receptors
      expressed on platelets with various extracellular matrix (ECM) proteins that may
      become exposed upon vascular injury. Studies of dynamic platelet adhesion to ECM
      coated substrates in conventional flow chambers require substantial fluid volumes
      and are difficult to perform with blood samples from a single laboratory mouse.
      Here we report dynamic platelet adhesion assays in two new microfluidic devices
      made of PDMS. Small cross-sections of the flow chambers in the devices reduce the
      blood volume requirements to <100 microl per assay, making the assays compatible
      with samples of whole blood obtained from a single mouse. One device has an array
      of 8 flow chambers with shear stress varying by a factor of 1.93 between adjacent
      chambers, covering a 100-fold range from low venous to arterial. The other device
      allows simultaneous high-resolution fluorescence imaging of dynamic adhesion of
      platelets from two different blood samples. Adhesion of platelets in the devices
      to three common ECM substrate coatings was verified to conform with published
      results. The devices were subsequently used to study the roles of extracellular
      and intracellular domains of integrin alphaIIbbeta3, a platelet receptor that is
      a central mediator of platelet aggregation and thrombus formation. The study
      involved wild-type mice and two genetically modified mouse strains and showed
      that the absence of the integrin impaired adhesion at all shear stresses, whereas
      a mutation in its intracellular domain reduced the adhesion only at moderate and
      high stresses. Because of small sample volumes required, the devices could be
      employed in research with genetically-modified model organisms and for adhesion
      tests in clinical settings with blood from neonates.

PMID- 18818804
TI  - A simple, disposable microfluidic device for rapid protein concentration and
      purification via direct-printing.
AB  - A facile and disposable microfluidic device for rapid protein concentration was
      fabricated by using a direct printing process. Two printed V-shaped microchannels
      in mirror image orientation were separated by a 100 mum wide toner gap. When a
      high electric field was applied across the two channels, nanofissures were formed
      by electric breakdown at the junction toner gap. This microfluidic device with
      nanofissures was used as a concentrator for protein. Negatively charged proteins
      were observed to concentrate at the anode side of the nanofissures upon
      application of an electric field across this junction. Using this device, about
      10(3)-10(5)-fold protein concentration was achieved within 10 min. Systematic
      investigation showed that the concentration mechanism could be explained by the
      ion exclusion-enrichment effect of the nanofissures. In addition, the present
      microchip device integrated both functions of concentration and purification were
      confirmed. This simple on chip protein preconcentration and purification device
      could be a disposable sample preparation component in printed microfluidic
      systems used for practical biochemical assays.

PMID- 18818805
TI  - On-chip screening method for cell migration genes based on a transfection
      microarray.
AB  - Cell migration plays a major role in a variety of biological processes and a
      detailed understanding of associated mechanisms should lead to advances in the
      medical sciences, for example, in drug discovery for cancer therapy. However, the
      traditional methods used for analysis of cell migration cannot easily be scaled
      up for high-throughput screening. In this study, we have attempted to develop a
      novel simple method for high-throughput phenotypic screening for the
      identification of genes that are required for cell migration. As the appropriate
      cell line for the method, we found NBT-L2b cells that would be suitable for
      screening of migration-related genes in our method without influence by other
      cellular processes. Moreover, the idea for printing both the labeled fibronectin,
      for identification of the starting region of a cell, and the green fluorescent
      protein (GFP) expression vector, for identification of cells that had been
      transfected with siRNA and of the end point of migration, brings a rapid and
      efficient high-throughput screening procedure. Our new method will lead to an
      enhanced understanding of cell migration.

PMID- 18818806
TI  - A platform for assessing chemotactic migration within a spatiotemporally defined
      3D microenvironment.
AB  - While the quantification of cell movement within defined biochemical gradients is
      now possible with microfluidic approaches, translating this capability to
      biologically relevant three-dimensional microenvironments remains a challenge. We
      introduce an accessible platform, requiring only standard tools (e.g. pipettes),
      that provides robust soluble factor control within a three-dimensional biological
      matrix. We demonstrate long-lasting linear and non-linear concentration profiles
      that were maintained for up to ten days using 34.5 muL solute volume. We also
      demonstrate the ability to superimpose local soluble factor pulses onto existing
      gradients via defined dosing windows. The combination of long-term and transient
      gradient characteristics within a three-dimensional environment opens the door
      for signaling studies that investigate the migratory behavior of cells within a
      biologically representative matrix. To this end, we apply temporally evolving and
      long-lasting gradients to study the chemotactic responses of human neutrophils
      and the invasion of metastatic rat mammary adenocarcinoma cells (MtLN3) within
      three-dimensional collagen matrices.

PMID- 18818807
TI  - Quantitative and qualitative analysis of a microfluidic DNA extraction system
      using a nanoporous AlO(x) membrane.
AB  - A nanoporous aluminium oxide membrane was integrated into a microfluidic system
      designed to extract hgDNA (human genomic DNA) from lysed whole blood. The
      effectiveness of this extraction system was determined by passing known
      concentrations of purified hgDNA through nanoporous membranes with varying pore
      sizes and measuring the amount of hgDNA deposited on the membrane while also
      varying salt concentration in the solution. DNA extraction efficiency increased
      as the salt concentration increased and nanopore size decreased. Based on these
      results, hgDNA was extracted from whole blood while varying salt concentration,
      nanopore size and elution buffer to find the conditions that yield the maximum
      concentration of hgDNA. The optimal conditions were found to be using a low-salt
      lysis solution, 100 nm pores, and a cationic elution buffer. Under these
      conditions the combination of flow and ionic disruption were sufficient to elute
      the hgDNA from the membrane. The extracted hgDNA sample was analysed and
      evaluated using PCR (polymerase chain reaction) to determine whether the eluted
      sample contained PCR inhibition factors. Eluted samples from the microfluidic
      system were amplified without any inhibition effects. PCR using extracted samples
      was demonstrated for several genes of interest. This microfluidic DNA extraction
      system based on embedded membranes will reduce the time, space and reagents
      needed for DNA analysis in microfluidic systems and will prove valuable for
      sample preparation in lab-on-a-chip applications.

PMID- 18818808
TI  - An integrated CMOS high voltage supply for lab-on-a-chip systems.
AB  - Electrophoresis is a mainstay of lab-on-a-chip (LOC) implementations of molecular
      biology procedures and is the basis of many medical diagnostics. High voltage
      (HV) power supplies are necessary in electrophoresis instruments and are a
      significant part of the overall system cost. This cost of instrumentation is a
      significant impediment to making LOC technologies more widely available. We
      believe one approach to overcoming this problem is to use microelectronic
      technology (complementary metal-oxide semiconductor, CMOS) to generate and
      control the HV. We present a CMOS-based chip (3 mm x 2.9 mm) that generates high
      voltages (hundreds of volts), switches HV outputs, and is powered by a 5 V input
      supply (total power of 28 mW) while being controlled using a standard computer
      serial interface. Microchip electrophoresis with laser induced fluorescence (LIF)
      detection is implemented using this HV CMOS chip. With the other advancements
      made in the LOC community (e.g. micro-fluidic and optical devices), these CMOS
      chips may ultimately enable 'true' LOC solutions where essentially all the
      microfluidics, photonics and electronics are on a single chip.

PMID- 18818809
TI  - Electronic control of elastomeric microfluidic circuits with shape memory
      actuators.
AB  - Recently, sophisticated fluidic circuits with hundreds of independent valves have
      been built by using multi-layer soft-lithography to mold elastomers. However,
      this shrinking of microfluidic circuits has not been matched by a corresponding
      miniaturization of the actuation and interfacing elements that control the
      circuits; while the fluidic circuits are small ( approximately 10-100 micron wide
      channels), the Medusa's head-like interface, consisting of external pneumatic
      solenoids and tubing or mechanical pins to control each independent valve, is
      larger by one to four orders of magnitude (approximately mm to cm). Consequently,
      the dream of using large scale integration in microfluidics for portable, high
      throughput applications has been stymied. By combining multi-layer soft
      lithography with shape memory alloys (SMA), we demonstrate electronically
      activated microfluidic components such as valves, pumps, latches and
      multiplexers, that are assembled on printed circuit boards (PCBs). Thus, high
      density, electronically controlled microfluidic chips can be integrated alongside
      standard opto-electronic components on a PCB. Furthermore, we introduce the idea
      of microfluidic states, which are combinations of valve states, and analogous to
      instruction sets of integrated circuit (IC) microprocessors. Microfluidic states
      may be represented in hardware or software, and we propose a control architecture
      that results in logarithmic reduction of external control lines. These
      developments bring us closer to building microfluidic circuits that resemble
      electronic ICs both physically, as well as in their abstract model.

PMID- 18818810
TI  - Modular microfluidics for gradient generation.
AB  - This paper describes a modular approach to constructing microfluidic systems for
      the generation of gradients of arbitrary profiles. Unlike most current
      microfluidic-based systems that have integrated architectures, we design several
      basic component modules such as distributors, combiners, resistors and collectors
      and connect them into networks that produce gradients of any profile at will.
      Using the system as a platform we can generate arbitrary gradient profiles that
      are tunable in real time. The key advantage of this system is that its operation
      is based on prefabricated components that are relatively simple. Particularly for
      non-specialists, the modular microfluidic system is easier to implement and more
      versatile compared to single, integrated gradient generators. The disadvantages
      associated with this system is that the total amount of liquids used is rather
      large compared with single chip-based systems. The system would be useful in
      simulating environments in vivo, e.g., studying how cells respond to temporal and
      spatial stimuli.

PMID- 18818811
TI  - Novel one-pot route to monodisperse thermosensitive hollow microcapsules in a
      microfluidic system.
AB  - We present a simple one-pot synthetic approach for the preparation of
      monodisperse thermo-sensitive poly(N-isopropylacrylamide) (PNIPAM) microcapsules
      in a microfluidic system. Based on the mechanism of shear force-driven break-off,
      aqueous droplets of monomer solution are continuously generated in an immiscible
      continuous phase containing photoinitiators. Under UV irradiation, activated
      initiators are diffused into the interface between the continuous phase and the
      aqueous droplets, which trigger polymerization of NIPAM monomers. The PNIPAM
      microcapsules produced are hollow microcapsules with a thin shell membrane, high
      monodispersity, and fast response to environmental temperature. In addition, the
      size of microcapsules produced can be manipulated by the flow rate of the
      continuous phase or aqueous phase and different concentrations of surfactant to
      control interfacial tension between continuous phase and aqueous phase.
      Furthermore, the versatility of this approach enables the preparation of
      monodisperse microcapsules having the capability to encapsulate various materials
      such as proteins and nanoparticles under mild conditions. The in situ
      microfluidic synthetic method provides a novel approach for the preparation of
      monodisperse hollow microcapsules via a one-pot route.

PMID- 18818812
TI  - Layer-to-layer parallel fluidic transportation system by addressable fluidic gate
      arrays.
AB  - This paper presents addressable fluidic gate arrays for a layer-to-layer parallel
      fluidic transportation system. The proposed addressable fluidic gate consists of
      double valves driven by pneumatic pressure. One of the double valves is
      controlled by the row channel and the other is controlled by the column channel
      for row/column addressing. Our study applies addressable fluidic gate arrays to
      layer-to-layer transportation beyond a typical in-plane fluidic network system.
      The layer-to-layer transportation makes it possible to collect targeted samples
      from a testing well plate. 3 x 3 fluidic gate arrays based on the proposed
      concept are developed and tested. A single PDMS valve (phi400 microm) can be
      closed by 75.0 kPa. The demonstrated fluidic system is based on all PDMS
      structures by taking account of its disposable use. This paper also reports a
      dome-shaped chamber for robust sealing and a switching valve with a bistable
      diaphragm for memory function.

PMID- 18818813
TI  - Polydimethylsiloxane-LiNbO3 surface acoustic wave micropump devices for fluid
      control into microchannels.
AB  - This paper presents prototypical microfluidic devices made by hybrid
      microchannels based on piezoelectric LiNbO(3) and polydimethylsiloxane. This
      system enables withdrawing micropumping by acoustic radiation in microchannels.
      The withdrawing configuration, integrated on chip, is here quantitatively
      investigated for the first time, and found to be related to the formation and
      coalescence dynamics of droplets within the microchannel, primed by surface
      acoustic waves. The growth dynamics of droplets is governed by the water
      diffusion on LiNbO(3), determining the advancement of the fluid front. Observed
      velocities are up to 2.6 mm s(-1) for 30 dBm signals applied to the interdigital
      transducer, corresponding to tens of nl s(-1), and the micropumping dynamics is
      described by a model taking into account an acoustic power exponentially decaying
      upon travelling along the microchannel. This straighforward and flexible
      micropumping approach is particularly promising for the withdrawing of liquids in
      lab-on-chip devices performing cycling transport of fluids and biochemical
      reactions.

PMID- 18818814
TI  - Room temperature UV adhesive bonding of CE devices.
AB  - A simple low temperature adhesive 'stamp-and-stick' bonding procedure for lab-on
      a-chip glass devices has been tested for capillary electrophoresis applications.
      This technique involves use of a mask aligner to transfer a UV-curable adhesive
      selectively onto the top CE substrate which is then aligned with and bonded to
      the bottom CE wafer. The entire bonding process can be carried out at room
      temperature in less than 30 minutes, involved only user-friendly laboratory
      operations, and provided a near 100% success rate. CE microchips made in this
      manner exhibited similar electroosmotic flow and separation characteristics as
      ones made via conventional high temperature thermal bonding. Equally important,
      the devices provided stable long-term performance over weeks of use, encompassing
      hundreds of individual CE runs without structural failure or any apparent change
      in operating characteristics. Finally, these devices exhibited excellent chip-to
      chip reproducibility. Successful adaptation of the stamp-and-stick approach did
      require the development and testing of new but easily implemented structural
      features which were incorporated into the chip design and whose nature is
      described in detail.

PMID- 18818815
TI  - Flexible fluidic microchips based on thermoformed and locally modified thin
      polymer films.
AB  - This paper presents a fundamentally new approach for the manufacturing and the
      possible applications of lab on a chip devices, mainly in the form of disposable
      fluidic microchips for life sciences applications. The new technology approach is
      based on a novel microscale thermoforming of thin polymer films as core process.
      The flexibility not only of the semi-finished but partly also of the finished
      products in the form of film chips could enable future reel to reel processes in
      production but also in application. The central so-called 'microthermoforming'
      process can be surrounded by pairs of associated pre- and postprocesses for micro
      and nanopatterned surface and bulk modification or functionalisation of the
      formed films. This new approach of microscale thermoforming of thin polymer film
      substrates overlaid with a split local modification of the films is called
      'SMART', which stands for 'substrate modification and replication by
      thermoforming'. In the process, still on the unformed, plane film, the material
      modifications of the preprocess define the locations where later, then on the
      spatially formed film, the postprocess generates the final local modifications.
      So, one can obtain highly resolved modification patterns also on hardly
      accessible side walls and even behind undercuts. As a first application of the
      new technology, we present a flexible chip-sized scaffold for three dimensional
      cell cultivation in the form of a microcontainer array. The spatially warped
      container walls have been provided with micropores, cell adhesion micropatterns
      and thin film microelectrodes.

PMID- 18818816
TI  - Fluorescent liquid-core/air-cladding waveguides towards integrated optofluidic
      light sources.
AB  - We have demonstrated fluorescent liquid-core/air-cladding (LA) waveguides
      suitable for use as integrated optofluidic light sources. These waveguides were
      fabricated by conventional soft lithography using poly(dimethylsiloxane) (PDMS).
      Two-phase stratified flows of air and ethylene glycol with fluorescent dye were
      generated along the PDMS channel. Compared to the liquid-core/liquid-cladding
      (L(2)) waveguide, the larger refractive index contrast of the LA waveguide
      resulted in stronger optical confinement. Specifically, the larger refractive
      index contrast led to experimentally achievable captured fractions (the amount of
      light to be coupled into the liquid core) as high as 22.8% and the measured
      propagation losses as low as 0.14 dB cm(-1). Furthermore, in our LA waveguides,
      diffusional mixing of the core and cladding fluids did not occur and the size of
      the core stream could be reversibly tuned simply by adjusting the flow rates of
      the two contiguous phases.

PMID- 18818817
TI  - Chemistry at surfaces.

PMID- 18818818
TI  - Molecular surface chemistry by metal single crystals and nanoparticles from
      vacuum to high pressure.
AB  - Model systems for studying molecular surface chemistry have evolved from single
      crystal surfaces at low pressure to colloidal nanoparticles at high pressure. Low
      pressure surface structure studies of platinum single crystals using molecular
      beam surface scattering and low energy electron diffraction techniques probe the
      unique activity of defects, steps and kinks at the surface for dissociation
      reactions (H-H, C-H, C-C, O=O bonds). High-pressure investigations of platinum
      single crystals using sum frequency generation vibrational spectroscopy have
      revealed the presence and the nature of reaction intermediates. High pressure
      scanning tunneling microscopy of platinum single crystal surfaces showed
      adsorbate mobility during a catalytic reaction. Nanoparticle systems are used to
      determine the role of metal-oxide interfaces, site blocking and the role of
      surface structures in reactive surface chemistry. The size, shape and composition
      of nanoparticles play important roles in determining reaction activity and
      selectivity and is covered in this tutorial review.

PMID- 18818819
TI  - The nature of the active site in heterogeneous metal catalysis.
AB  - This tutorial review, of relevance for the surface science and heterogeneous
      catalysis communities, provides a molecular-level discussion of the nature of the
      active sites in metal catalysis. Fundamental concepts such as "Bronsted-Evans
      Polanyi relations" and "volcano curves" are introduced, and are used to establish
      a strict partitioning between the so-called "electronic" and "geometrical"
      effects. This partitioning is subsequently employed as the basis for defining the
      concept "degree of structure sensitivity" which can be used when analyzing the
      structure sensitivity of catalytic reactions.

PMID- 18818820
TI  - Catalytic reaction energetics by single crystal adsorption calorimetry:
      hydrocarbons on Pt(111).
AB  - Single crystal adsorption calorimetry provides essential information about the
      energetics of surface reactions on well-defined surfaces where the adsorbed
      reaction products can be clearly identified. In this tutorial review, we cover
      the essentials of that technique, with emphasis on our lab's recent advances in
      sensitivity and temperature range, and demonstrate what can be achieved through a
      review of selected example studies concerning adsorption and dehydrogenation of
      hydrocarbons on Pt(111). A fairly complete reaction enthalpy diagram is presented
      for the dehydrogenation of cyclohexane to benzene on Pt(111).

PMID- 18818821
TI  - A surface science approach to ultrafast electron transfer and solvation dynamics
      at interfaces.
AB  - Excess electrons in polar media, such as water or ice, are screened by
      reorientation of the surrounding molecular dipoles. This process of electron
      solvation is of vital importance for various fields of physical chemistry and
      biology as, for instance, in electrochemistry or photosynthesis. Generation of
      such excess electrons in bulk water involves either photoionization of solvent
      molecules or doping with e.g. alkali atoms, involving possibly perturbing
      interactions of the system with the parent-cation. Such effects are avoided when
      using a surface science approach to electron solvation: in the case of polar
      adsorbate layers on metal surfaces, the substrate acts as an electron source from
      where photoexcited carriers are injected into the adlayer. Besides the
      investigation of electron solvation at such interfaces, this approach allows for
      the investigation of heterogeneous electron transfer, as the excited solvated
      electron population continuously decays back to the metal substrate. In this
      manner, electron transfer and solvation processes are intimately connected at any
      polar adsorbate-metal interface. In this tutorial review, we discuss recent
      experiments on the ultrafast dynamics of photoinduced electron transfer and
      solvation processes at amorphous ice-metal interfaces. Femtosecond time-resolved
      two-photon photoelectron spectroscopy is employed as a direct probe of the
      electron dynamics, which enables the analysis of all elementary processes: the
      charge injection across the interface, the subsequent electron localization and
      solvation, and the dynamics of electron transfer back to the substrate. Using
      surface science techniques to grow and characterize various well-defined ice
      structures, we gain detailed insight into the correlation between adsorbate
      structure and electron solvation dynamics, the location (bulk versus surface) of
      the solvation site, and the role of the electronic structure of the underlying
      metal substrate on the electron transfer rate.

PMID- 18818822
TI  - Scanning tunneling microscopy as a tool to study catalytically relevant model
      systems.
AB  - The surface science approach to catalysis, pioneered by 2007 Nobel Laureate in
      chemistry Gerhard Ertl, has helped revolutionize our understanding of
      heterogeneous catalysis at the atomic level. In this tutorial review we show how
      the scanning tunnelling microscope (STM), in combination with this surface
      science approach, is a very important tool for the study of catalytically
      relevant model systems. We illustrate how the high spatial and temporal
      resolution of the STM can be used to obtain quantitative information on
      elementary processes involved in surface catalyzed reactions. Furthermore, we
      show that the STM is an outstanding surface science tool to bridge the materials
      gap and the pressure gap between surface science experiments and real catalysis.
      Finally, we show that we are approaching an era where the atomic-scale insight
      gained from fundamental STM surface science studies can be used for the rational
      design of new catalysts from first principles.

PMID- 18818823
TI  - Automotive catalysis studied by surface science.
AB  - In this tutorial review I discuss the significant impact that surface science has
      had on our understanding of the catalytic phenomena associated with automobile
      exhaust depollution catalysis. For oxidation reactions it has generally been
      found that reactions are self-poisoned at low temperatures by the presence of
      strongly adsorbed reactants (such as molecular CO and NO), and that the rapid
      acceleration in rate at elevated temperatures (often called 'light-off') is due
      to the desorption of such adsorbates, which then frees up sites for dissociation
      and hence for oxidation reactions. In some circumstances such autocatalytic
      phenomena can then manifest themselves as oscillatory reactions which can vary in
      rate in both space and time. For NO reduction, the efficiency of depollution (by
      production of molecular nitrogen) is strongly affected by the nature of the metal
      used. Rh is extremely effective because it can dissociate NO much more readily
      than metals such as Pd and Pt, enabling oxygen removal (by reaction with CO to
      CO2) even at room temperature. Rh is also very selective in producing
      predominantly N2, rather than N2O. NOx storage and reduction (NSR) is an
      important recent development for removal of NOx under the highly oxidising
      conditions of a lean-burn engine exhaust, and the strategy involves storing NOx
      on BaO under oxidising conditions followed by the creation of reducing conditions
      to de-store and reduce it to nitrogen. By the use of STM it has been shown that
      this storage process is extremely facile, occurring fast even under UHV
      conditions, and that the storage occurs on BaO in the vicinity of Pt, with most
      of the oxide being converted to nitrate.

PMID- 18818824
TI  - Ultrafast charge transfer at surfaces accessed by core electron spectroscopies.
AB  - Charge transfer at surfaces, which is very important for surface photochemistry
      and other processes, can be extremely fast. This tutorial review shows how high
      resolution correlated excitation/decay spectroscopies of core excitations can be
      used to obtain charge transfer times at surfaces around or below 1 fs. Some
      results are described in more detail, and their meaning and theoretical modelling
      are discussed. A brief comparison to laser methods shows that there are
      differences in the processes they look at.

PMID- 18818825
TI  - Oxide ultra-thin films on metals: new materials for the design of supported metal
      catalysts.
AB  - Ultrathin oxide films on metals offer new opportunities for the design of
      supported nanoclusters with potential use in catalysis. This requires a
      characterization at the atomistic level of the structure and composition of the
      thin film, of its morphology and defect structure. A proper selection of
      metal/oxide interface, film thickness, lattice mismatch, etc. makes it possible
      to prepare collections of supported metal particles with novel properties. This
      critical review describes some illustrative examples, emphasizes the role of the
      interplay between theory and experiment, and relates some recent findings related
      to the possibility to control the charge state of a supported nanoparticle on an
      ultrathin oxide film (211 references).

PMID- 18818826
TI  - Unraveling molecular transformations on surfaces: a critical comparison of
      oxidation reactions on coinage metals.
AB  - The coinage metals, copper, silver, and gold, have unique characteristics for
      selective oxidation catalysis, particularly for partial oxidation of alcohols and
      olefins. A basic understanding of surface chemistry at the molecular level can
      help facilitate the improvement of current catalytic processes and the designing
      of new catalytic systems. In this critical review, the current state of knowledge
      of these reactions is reviewed. First, both the experimental and theoretical
      methods necessary for understanding surface reactivity are discussed with a
      specific set of examples directly related to these reactions. Next the state of
      understanding of the surface chemistry of the oxidation reactions of alcohols and
      olefins on these three coinage metals is reviewed and the reaction pathways are
      compared. Clear relationships between the low pressure surface science studies
      and more practical catalytic conditions are illustrated. Finally, recent
      theoretical advances in this area are discussed as well as possible future
      directions in this field (132 references).

PMID- 18818827
TI  - The local structure of molecular reaction intermediates at surfaces.
AB  - A critical review is presented of the results of (experimental) quantitative
      structural studies of molecular reaction intermediates at surfaces; i.e.
      molecular species that do not exist naturally in the gas phase and, in most
      cases, are implicated in surface catalytic processes. A brief review of the main
      experimental methods that have contributed to this area is followed by a summary
      of the main results. Investigated species include: carboxylates, RCOO-
      (particularly formate, but also deprotonated amino acids); methoxy, CH3O-;
      carbonate, CO3; ethylidyne, CH3C-; NHx and SOx species; cyanide, CN. As far as
      possible in the limited range of systems studied, a few general trends are
      identified (108 references).

PMID- 18818828
TI  - In-silico investigations in heterogeneous catalysis--combustion and synthesis of
      small alkanes.
AB  - In this critical review, we cover first-principles density functional
      calculations relevant to alkane oxidation and synthesis over transition metal
      catalysts. For oxidation, we focus upon Pt, Rh, Pd and Ni surfaces, while for
      synthesis we consider Co, Ru, Fe and Ni. Throughout, we emphasise the insight to
      be gained by thinking of each kind of reaction as the inverse of the other, with
      the directionality determined simply by the choice of metal catalyst and the
      reaction conditions. We highlight particularly the role of low-coordination sites
      (steps, kinks, etc.) and the emerging consensus over the importance of the formyl
      intermediate in facilitating the rate-determining step (249 references).

PMID- 18818829
TI  - Nanoscale surface chemistry over faceted substrates: structure, reactivity and
      nanotemplates.
AB  - Faceting is a form of self-assembly at the nanometre-scale on adsorbate-covered
      single-crystal surfaces, occurring when an initially planar surface converts to a
      "hill and valley" structure, exposing new crystal faces of nanometre-scale
      dimensions. Planar metal surfaces that are rough on the atomic scale, such as bcc
      W(111), fcc Ir(210) and hcp Re(1231), are morphologically unstable when covered
      by monolayer films of oxygen, or by certain other gases or metals, becoming
      "nanotextured" when heated to temperatures above approximately 700 K. Faceting is
      driven by surface thermodynamics (anisotropy of surface free energy) but
      controlled by kinetics (diffusion, nucleation). Surfaces can spontaneously
      rearrange to minimize their total surface energy (by developing facets), even if
      this involves an increase in surface area. In this critical review, we discuss
      the structural and electronic properties of such surfaces, and first principles
      calculations are compared with experimental observations. The utility of faceted
      surfaces in studies of structure sensitive reactions (e.g., CO oxidation, ammonia
      decomposition) and as templates for growth of metallic nanostructures is explored
      (122 references).

PMID- 18818830
TI  - Chemical reactions on rutile TiO2(110).
AB  - Understanding the surface chemistry of TiO2 is key to the development and
      optimisation of many technologies, such as solar power, catalysis, gas sensing,
      medical implantation, and corrosion protection. In order to address this,
      considerable research effort has been directed at model single crystal surfaces
      of TiO2. Particular attention has been given to the rutile TiO2(110) surface
      because it is the most stable face of TiO2. In this critical review, we discuss
      the chemical reactivity of TiO2(110), focusing in detail on four
      molecules/classes of molecules. The selected molecules are water, oxygen,
      carboxylic acids, and alcohols-all of which have importance not only to industry
      but also in nature (173 references).

PMID- 18818831
TI  - Recent progress in theoretical analysis of vibrational sum frequency generation
      spectroscopy.
AB  - This article summarizes the computational analysis of the vibrational sum
      frequency generation (SFG) spectroscopy with molecular dynamics simulation. The
      analysis allows direct comparison of experimental SFG spectra and microscopic
      interface structure obtained by molecular simulation, and thereby obviates
      empirical fitting procedures of the observed spectra. In the theoretical
      formulation, the frequency-dependent nonlinear susceptibility of an interface is
      calculated in two ways, based on the energy representation and time-dependent
      representation. The application to aqueous interfaces revealed a number of new
      insights into the local structure of electrolyte interfaces and the
      interpretation of SFG spectroscopy.

PMID- 18818832
TI  - Determination of the rate of a fast exchanging coordinated molecule in a
      lanthanide(III) complex by proton NMR.
AB  - An elementary procedure is proposed and applied to study the exchange rate of a
      solvent or solute molecule bound to a complexed paramagnetic Ln(III) ion, other
      than Gd(III), from the measured longitudinal and transverse relaxation rates and
      paramagnetic resonance frequency shift at a given temperature.

PMID- 18818833
TI  - An ambipolar host material provides highly efficient saturated red PhOLEDs
      possessing simple device structures.
AB  - A highly efficient red electrophosphorescent device exhibited saturated red
      emission and an impressive external quantum efficiency [eta(ext) = 10.8% (ph/el)]
      with simple device configuration of doping an iridium complex (Mpq(2)Iracac) into
      a novel ambipolar spiro-configured donor-acceptor host material (D2ACN) has been
      developed.

PMID- 18818834
TI  - Optimising an artificial neural network for predicting the melting point of ionic
      liquids.
AB  - We present an optimised artificial neural network (ANN) model for predicting the
      melting point of a group of 97 imidazolium salts with varied anions. Each cation
      and anion in the model is described using molecular descriptors. Our model has a
      mean prediction error of 1.30%, a regression coefficient of 0.99 and a mean P
      value of 0.92. The ANN's prediction performance depends mainly on the anion size.
      In particular, the prediction error decreases as the anion size increases. The
      high statistical relevance makes this model a useful tool for predicting the
      melting points of imidazolium-based ionic liquids.

PMID- 18818835
TI  - Quantum chemical studies on hydrogen adsorption in carbon-based model systems:
      role of charged surface and the electronic induction effect.
AB  - Quantum chemical studies on the molecular hydrogen adsorption in a six-membered
      carbon ring has been undertaken to mimic the adsorption process in carbon
      nanotubes, considering the fact that the six-membered carbon ring is found to be
      one of the basic units of the carbon nanotubes and fullerenes. Our results reveal
      that the carbon surface as such is not a good candidate for hydrogen adsorption
      but a charged surface created by doping of an alkali metal atom can play an
      important role for the improvement in adsorption of molecular hydrogen. The
      strength of hydrogen interaction as well as the number of hydrogen molecules that
      can be adsorbed on the system is found to depend on the nature of the cation
      doped in the system. We have also studied the role of electronic induction by
      substituting different functional groups in the model system on the hydrogen
      adsorption energy. The results demonstrate that the binding energy of the cation
      with the carbon surface as well as the hydrogen adsorption energy can be tuned
      significantly through the use of suitable substituents. In addition, we have
      shown that the extended planar or the curved carbon surface of the coronene
      system alone may not be suitable for an effective molecular hydrogen adsorption.
      In essence, our results reveal that the ionic surface with a significant degree
      of curvature will enhance the hydrogen adsorption effectively.

PMID- 18818836
TI  - Configurational probabilities for monomers, dimers and trimers in fluids.
AB  - A new analytical approach is proposed to model aggregation of molecules with
      isotropic, nearest-neighbor, attractive interactions. By treating the clustering
      process as a chain reaction, equations with the exact high temperature limit are
      derived by evaluating the occupation probabilities of nearest neighbors based on
      the Ono-Kondo approach for a hexagonal lattice to calculate the configurational
      probabilities of i-mers (i = 1, 2, 3). Equilibrium constants for dimers and
      trimers are calculated based on the configurational probability data. The
      proposed model agrees well with Monte Carlo simulations at medium and high
      temperatures. At low temperatures, the model can be improved by considering the
      full set of site densities in the first shell of a central trimer. Approximate
      analytical solutions derived from exact calculations of the grand partition
      function for monomer adsorption on a 4 x N hexagonal lattice with cylindrical
      boundary conditions also are presented.

PMID- 18818837
TI  - The chaotic sequences in the Bray-Liebhafsky reaction in an open reactor.
AB  - Attractor reconstruction is done from the time series obtained by experimental
      investigation and by deterministic and stochastic simulation of the Bray
      Liebhafsky oscillatory reaction. The appearance of deterministic chaos is
      confirmed and proven by both simulation and experiment, determining Lyapunov
      exponents for the sequences of flow rate values, as the control parameter.
      Moreover, unusual chaotic series were additionally recorded in the experiments,
      which cannot be found in deterministic numerical simulations. Therefore, an
      explanation of the difference between the dynamic behavior in the experiment and
      the deterministic simulation was sought and stochastic simulations based on the
      same reaction model were particularly useful. The fine structure of the chaotic
      windows, derived from the analysis of deterministic simulations in the range of
      flow rate values, made the system highly susceptible to noise induced effects, in
      general.

PMID- 18818838
TI  - Solid-state synthesis of LiBD(4) observed by in situ neutron diffraction.
AB  - The synthesis of Li[(11)BD(4)] from LiB and D(2) (p = 180 bar) is investigated by
      in situ neutron diffraction. The onset of the Li[(11)BD(4)] formation is observed
      far below the temperatures reported so far for the reaction from the pure
      elements, indicative of a lower activation barrier. We attribute the improved
      formation behavior to the breaking of the rigid boron lattice and intermixing of
      the elements on an atomic level when forming the binary compound LiB. The
      reaction starts with the decomposition of the initial LiB compound and the
      formation of LiD. At 623 K LiBD(4) starts to form. However, under the given
      experimental conditions (maximal temperature = 773 K) a complete reaction was not
      achieved; there is still residual LiD present.

PMID- 18818839
TI  - Electrochemical co-deposition of Ti n+ phases with gold in ionic liquids.
AB  - The electro-deposition of titanium from two different classes of ionic liquids
      has been studied. Gold ions in solution have been used as an additive in order to
      provide a stable nucleation site for titanium to deposit on via a co-deposition
      process. Despite evidence from previous literature, it was found that it was not
      possible to reduce titanium from the +4 state to titanium (0) due to problems of
      redox cycling and solubility of reduced titanium species in the various ILs
      trialled. It was however found that gold was a very effective nucleating agent
      for these reduced titanium species and that successful mixed Ti(n+)/gold electro
      deposits were obtained. The content of titanium in these species could be varied
      according to the conditions and IL used.

PMID- 18818840
TI  - Nanostructured Cu and Cu@Cu(2)O core shell catalysts for hydrogen generation from
      ammonia-borane.
AB  - Copper nanoparticles have been prepared by the solvated metal atom dispersion
      (SMAD) method. Oxidation of the SMAD prepared copper colloids resulted in
      Cu@Cu(2)O core shell structures (7.7 +/- 1.8 nm) or Cu(2)O nanoparticles
      depending on the reaction conditions. The nano Cu, Cu@Cu(2)O core shell, and
      Cu(2)O particles were found to be catalytically active for the generation of
      hydrogen from ammonia-borane either via hydrolysis or methanolysis reaction.

PMID- 18818841
TI  - Microkinetic simulations of the oxidation of CO on Pd based nanocatalysis: a
      model including co-dependent support interactions.
AB  - The catalysed oxidation of CO using mass-selected Pd(13) clusters supported on
      thin MgO films was modelled using a microkinetic simulation of the reaction. The
      model of the system includes reverse spill-over calculations which were
      intrinsically incorporated into the formulation of the kinetics. The spill-over
      model is based on a capture-zone approach including a co-dependence on the
      variables of the kinetic equations. The experimental values were determined using
      dual pulsed-molecular beam measurements and recorded at a range of temperatures.
      The experiment allowed the turn-over frequency and reaction probability to be
      determined as a function of mole fraction. Comparison of the kinetic model with
      the experimental data gives excellent agreement and strongly highlights the
      importance of substrate effects. In particular, the origin of the low temperature
      catalysis of the Pd clusters is elucidated. The model allows the mole fraction
      and temperature dependent values such as the sticking coefficients for these
      clusters to be predicted.

PMID- 18818842
TI  - Metal-to-ligand and ligand-to-metal charge transfer in thin films of Prussian
      blue analogues investigated by X-ray absorption spectroscopy.
AB  - A series of thin films of Prussian blue analogues is investigated by X-ray
      absorption spectroscopy (XAS) at the Fe, Co and Mn L(2,3)-edges. The ligand field
      multiplet theory enables us to examine accurately the electronic structure of
      these materials. Experimental XAS spectra of CoFe Prussian blue analogues are
      successfully reproduced using a ground state configuration including metal-to
      ligand (MLCT) and ligand-to-metal charge transfer (LMCT) at the Co and Fe L(2,3)
      edges. In particular, a huge improvement is achieved for satellite peaks at the
      Co(iii) L(2,3)-edges compared to previous calculations in the literature based on
      LMCT effects only. On the other hand, XAS spectra of MnFe analogues synthesized
      for the first time, can be reproduced conveniently by taking into account either
      MLCT or LMCT depending on the conditions of the sample preparation. For each thin
      film, the proportion of the different oxidation states of Co, Fe and Mn is
      evaluated. Unexpectedly, this analysis reveals the presence of a significant
      amount of a reduced phase, which turns out to be strongly dependent on the sample
      synthesis and storage conditions.

PMID- 18818843
TI  - Orientational dynamics of a charge transfer complex in cyclodextrin cavity as
      receptor.
AB  - This paper reports the structure and dynamics of a twisted intermolecular charge
      transfer molecule 2-(4-(dimethylamino) styryl)-1-methylpyridinium iodide (o
      DASPMI) included inside alpha-, beta- and gamma-cyclodextrin, investigated by
      using steady state and time-resolved emission spectroscopy and also theoretical
      modeling. A nice 1 : 1 inclusion complex with beta-CD in the excited state could
      be found with the dimethylamino group of the molecule sticking out as revealed
      from steady state and time-resolved emission. The inclusion complex has a longer
      decay time compared to that in neat water. Time-resolved anisotropy decay has
      been used to study the rotational dynamics of the molecule inside cyclodextrin
      cavity. The average angular structure of the inclusion complex as found from
      semiempirical PM3 calculations corroborates excellently the experimental results
      of angular orientation in beta-CD. The minimum energy of the complex is found to
      be nearly 5 A in the length of the molecule with the dimethylamino part sticking
      out in the bulk water. Hydrogen bonding at the rim hinders the inclusion complex
      of o-DASPMI in gamma-CD and instead it produces association at the rim. Hydrogen
      bond breaker urea breaks the bonding of o-DASPMI with the rim of gamma-CD and the
      formation of inclusion complex with gamma-CD ensues.

PMID- 18818844
TI  - Temperature stability and photodimerization kinetics of beta-cinnamic acid and
      comparison to its alpha-polymorph as studied by solid-state NMR spectroscopy
      techniques and DFT calculations.
AB  - Photoreactions of the alpha- and beta-polymorphs of trans-cinnamic acid were
      studied by (13)C CPMAS solid-state nuclear magnetic resonance spectroscopy, and
      the reactants and products were spectroscopically characterized in detail.
      Chemical shifts and chemical shift anisotropy tensors calculated using density
      functional theory (DFT) were found to be in good agreement with the experimental
      results and helped to identify the polymorphs and the individual assignments of
      reactant and photoproduct carbon atoms. The beta-polymorph is metastable. Its
      transformation into the alpha-cinnamic acid polymorph is monitored by temperature
      dependent (13)C NMR spectroscopy. The transformation occurs at a very slow rate
      at room temperature but is highly accelerated at elevated temperatures. Analysis
      of the kinetics of the photoreaction shows that the beta-polymorph progresses at
      a slower rate compared to that of alpha-cinnamic acid. Based on chemical shift
      tensor values of reactants and products as obtained from 2D PASS spectra, the
      difference in reaction rates is suggested to be due to the higher amount of
      molecular reorientation of functional groups upon photoreaction and the larger
      distance between the reacting double bonds.

PMID- 18818845
TI  - Dissociations of copper(II)-containing complexes of aromatic amino acids: radical
      cations of tryptophan, tyrosine, and phenylalanine.
AB  - The dissociations of two types of copper(II)-containing complexes of tryptophan
      (Trp), tyrosine (Tyr), or phenylalanine (Phe) are described. The first type is
      the bis-amino acid complex, [Cu(II)(M)(2)].(2+), where M = Trp, Tyr, or Phe; the
      second [Cu(II)(4Cl-tpy)(M)].(2+), where 4Cl-tpy is the tridendate ligand 4'
      chloro-2,2':6',2''-terpyridine. Dissociations of the Cu(ii) bis-amino acid
      complexes produce abundant radical cation of the amino acid, M.(+), and/or its
      secondary products. By contrast, dissociations of the 4Cl-tpy-bearing ternary
      complexes give abundant M.(+) only for Trp. Density functional theory (DFT)
      calculations show that for Tyr and Phe, amino-acid displacement reactions by
      H(2)O and CH(3)OH (giving [Cu(II)(4Cl-tpy)(H(2)O)].(2+) and [Cu(II)(4Cl
      tpy)(CH(3)OH)].(2+)) are energetically more favorable than dissociative electron
      transfer (giving M.(+) and [Cu(I)(4Cl-tpy)](+)). The fragmentation pathway common
      to all these [Cu(II)(4Cl-tpy)(M)].(2+) ions is the loss of NH(3). DFT
      calculations show that the loss of NH(3) proceeds via a "phenonium-type"
      intermediate. Dissociative electron transfer in [Cu(II)(4Cl-tpy)(M-NH(3))].(2+)
      results in [M-NH(3)].(+). The [Phe-NH(3)] (+) ion dissociates facilely by
      eliminating CO(2) and giving a metastable phenonium-type ion that rearranges
      readily into the styrene radical cation.

PMID- 18818846
TI  - Photo- and solvatochromic properties of nitrobenzospiropyran in ionic liquids
      containing the [NTf2]- anion.
AB  - The photo-, thermo- and solvatochromic properties of 2,3-dihydro-1',3',3'
      trimethyl-6-nitrospiro-[1-benzopyran-2,2'-1H-indole] (BSP-NO(2)) were studied in
      ILs containing the anion [NTf(2)](-) by UV-Vis absorption spectroscopy, ab initio
      molecular orbital theory and density functional theory (DFT) calculations. It was
      found that the kinetics and thermodynamics of the BSP-NO(2) <--> MC (merocyanine)
      equilibrium was sensitive to the nature of the cation. It was also observed that
      the imidazolium cation can form a through-space orbital interaction with the MC
      isomer, rather than a simple electrostatic interaction, thus preventing the MC
      conversion back to the BSP-NO(2) isomer. The BSP-NO(2) <--> MC equilibrium thus
      serves as a model system for studying modes of interaction of the cations in
      ionic liquids.

PMID- 18818847
TI  - Protocol to predict the dry skin benefit from the unique in-shower body lotion
      product form.
AB  - A controlled exposure method was developed to predict dry skin improvement from a
      new in-shower body lotion product form. An in-shower body lotion is used in the
      shower after cleansing, and methods for cleansers and leave-on lotions are not
      applicable. Protocol parameters were chosen on the basis of consumer habits and
      practices studies and randomized clinical testing. The resulting protocol is
      consumer-relevant, and reliably and reproducibly predicts dry skin improvement
      from the in-shower body lotion product form.

PMID- 18818848
TI  - Visualization and quantification of skin barrier perturbation induced by
      surfactant-humectant systems using two-photon fluorescence microscopy.
AB  - In order to visualize the effects of aqueous surfactant-humectant systems on the
      skin barrier, an in vitro two-photon fluorescence microscopy (TPM) study,
      including dual-channel visualization, was carried out. TPM is a non-invasive
      imaging technique based on two-photon induced nonlinear excitations of
      fluorophores, with the capability for deep-tissue imaging (up to several hundred
      micrometers). The following aqueous solutions of surfactants, a humectant, and a
      surfactant+humectant mixture that contacted pig full-thickness skin (p-FTS) were
      studied: (i) a harsh surfactant solution-sodium dodecyl sulfate (SDS) (1 wt%);
      (ii) a harsh surfactant+humectant solution-SDS (1 wt%) + glycerol (10 wt%); (iii)
      a mild surfactant solution-sodium cocoyl isethionate (SCI) (1 wt%); (iv) a
      control solution-phosphate-buffered saline (PBS); and (v) a humectant solution
      glycerol (10 wt%). Sulforhodamine B (SRB), a hydrophilic fluorescent probe, was
      used to visualize the effects of aqueous contacting solutions i-v on the skin
      barrier morphology. The results of the TPM visualization study revealed that SDS
      induces corneocyte damage by denaturing keratins and creating intracorneocyte
      penetration pathways. On the other hand, SDS+glycerol did not significantly
      induce corneocyte damage. The dual-channel TPM images corresponding to aqueous
      contacting solutions iii-v showed low SRB penetration into the corneocytes, as
      well as localization of the SRB probe within the lipid bilayers surrounding the
      corneocytes of the SC. Through a quantification of the amount of SRB that
      penetrated into the skin as a function of skin depth, we found that adding
      glycerol to an SDS aqueous contacting solution can significantly reduce the SDS
      induced penetration depth of SRB, which provides evidence of the ability of
      glycerol to mitigate SDS-induced skin barrier perturbation. The distribution of
      SRB in the p-FTS samples was analyzed using a theoretical model that quantified
      changes in the skin aqueous pore characteristics induced by aqueous contacting
      solutions i, ii, iii, and v, relative to aqueous contacting solution iv, the
      control. The results of the theoretical model indicate the following ranking
      order in the extent of perturbation to the skin aqueous pores (from the highest
      to the lowest): i > ii > iii > iv > v. The development of such an in vitro visual
      ranking methodology, including quantification using TPM, can potentially reduce
      many costly in vivo screening procedures, thereby significantly reducing the cost
      and time-to-market of new cosmetic formulations containing surfactants and
      humectants.

PMID- 18818849
TI  - Microbiological assessment of the ultraviolet screening effect of sunscreen
      preparations.
AB  - The purpose of this study was the development of a microbiological method for the
      assessment of the ultraviolet (UV) screening effect of sunscreen preparations and
      determination of their sun protection factor. The method is based on the lethal
      effect of UV radiation on Escherichia coli (E. coli ) and the protective ability
      of sunscreens. The time of UV exposure required for the reduction of the E. coli
      viable count by 90% (decimal reduction time, DRT) was used as the photoprotection
      assessment parameter. The method was tested by assessing the effect of selected
      experimental variables on the DRT. The suitability of the method as a quality
      control tool for sunscreen preparations was then checked by assessing the
      influence of selected formulation variables on the photoprotective effect of a
      series of o/w emulsion formulations with different compositions. The method
      proved valid for detecting changes in the photoprotective effect of a market
      sunscreen product as a result of modifying experimental conditions. It also
      proved valid for ranking market sunscreen products according to their UV
      screening effect. Equally important, the method could successfully detect changes
      in the photoprotective effect of sunscreen test formulations as a function of the
      concentration and type of the sunscreen agents.

PMID- 18818850
TI  - True porosity measurement of hair: a new way to study hair damage mechanisms.
AB  - This study employs a novel method, gas sorption (1), to quantify the porosity
      characteristics of hair by determining total pore volume, adsorption pore-size
      distribution, and the surface area of damaged hair. Damage mechanisms were
      studied by comparing the different pore volume and surface area resulting from
      two different types of damage: chemical and UV. Hair color measurement and
      tensile strength, both reflecting the changes in hair cortex, were also employed
      in this study. The results suggest that hair damage caused by oxidative bleach
      and UV oxidation follows different pathways. Chemical damage (oxidative bleach)
      nearly triples the hair surface area in the first minute of bleaching due to the
      increase in the number of pores, followed by a sudden drop after 10 min of
      bleaching from smaller pores breaking down into larger ones. In contrast, UV
      damage shows an immediate loss in surface area in the first 200 hr of exposure
      and a gradual increase as exposure time continues.

PMID- 18818851
TI  - Characterization of curved hair of Japanese women with reference to internal
      structures and amino acid composition.
AB  - The variation of hair curvature in Japanese women was quantitatively investigated
      and the structure of curved hair was characterized with transmission electron
      microscopy (TEM) and amino acid analysis. Two hundred and thirty Japanese women
      volunteers, aged from 10 to 70 years, were randomly selected. The evaluation of
      the volunteers' natural hair shape showed that 53% of Japanese women have
      straight hair, while the remaining 47% have curved hair (varying from a slightly
      wavy shape to a frizzy style). The average curl radius of the volunteers' hair
      was determined to be 4.4 +/- 2.3 cm, and ranged widely from 0.6 to 16 cm. The TEM
      observation of curved hair fiber revealed an inhomogenous internal structure
      between the outer and inner regions of the curved shape. In relation to the
      inhomogeneous structure of the curved hair, different amino acid composition of
      the hair keratin was observed between the outer and inner regions. Interestingly,
      these results of the TEM observation and the amino acid analysis are analogous to
      the difference between the ortho- and paracortical cells in wool fibers,
      suggesting the universal structure of curved mammalian hair.

PMID- 18818855
TI  - [Personality differences between substance addicts and general population. Study
      of clinical cases with matched controls using Cloninger's TCI-R.]
AB  - Objective: This article explores differences in personality traits between
      subjects with substance addiction in treatment and subjects from the general
      population matched in the variables sex, age and educational level. Material and
      method: Consecutive sampling was used to obtain a sample of participants
      undergoing treatment for addictive disorders at a public centre (CAD 4). A sample
      of the general population was obtained by means of the snowball technique. Only
      pairs (one participant from each sample) with the same age, sex and educational
      level were considered. In this way, 55 pairs were obtained. Cloninger's TCI-R was
      used and the global results were compared, crossing all variables. Results:
      Significant and consistent differences were found in just two traits: Novelty
      Seeking, greater in addicts, and Self- Directedness, greater in general
      population. Conclusions: Data strongly suggest that observed differences are not
      previous, but consecutive to the addiction, it being apparent that the effects of
      the substances and the psychosocial conditions associated with their consumption
      are what exacerbates or blocks development of the traits. Findings are related to
      studies linking these variables with neuropsychological functions, and the
      inclusion of this neuropsychological perspective is strongly proposed for
      application to the assessment and treatment of addictive disorders.

PMID- 18818856
TI  - The Tachikawa cohort of motor vehicle accident study investigating psychological
      distress: design, methods and cohort profiles.
AB  - BACKGROUND: The Tachikawa cohort of motor vehicle accident (TCOM) Study has been
      carried out in Tokyo since 2004. This study examined the association of medical
      and psychosocial variables evaluated shortly after admission to the acute
      critical care center with long-term psychiatric morbidity risk in patients with
      accidental injuries. METHODS: Between May 2004 and January 2008, patients with
      accidental injury consecutively admitted were recruited to the TCOM Study.
      Psychiatric morbidity as a primary endpoint was measured using a structured
      clinical interview at 1, 6, 18 and 36 months after involvement in a motor vehicle
      accident (MVA). The baseline investigation consisted of self-administered
      questionnaires concerning acute psychological responses and personality. Medical
      information was obtained from patients' medical charts. Various socio-demographic
      data, health-related habits and psychosocial factors were assessed by interview.
      To examine potential biomarkers of psychological distress, blood samples were
      collected. RESULTS: Out of 344 patients who were asked to participate in this
      study, 300 (87%) patients with MVA-related injury were enrolled. Corresponding
      rates for the questionnaires on psychological responses and blood sampling were
      98-99 and 79%, respectively. The cohort sample was composed of 78% men; the
      median age was 34 years; and 45% of the participants were motorcycle drivers.
      CONCLUSIONS: The TCOM Study should prove useful for researchers examining the
      association between bio-psychosocial variables and psychological distress and may
      contribute to the formation of a framework for providing care for patients with
      MVA-related injury.

PMID- 18818857
TI  - Psychosocial adaptation of adolescent migrants in a Swiss community survey.
AB  - OBJECTIVE: The aim of this study was to compare psychosocial adaptation in
      adolescent (first generation) migrants, double-citizens (mainly second generation
      with one migrant parent), and native Swiss, and to compare migrants from various
      European regions. METHOD: Data from a community survey were based on 1,239
      participants (mean age 13.8, SD = 1.6 years) with 996 natives, 55 double
      citizens, and 188 migrants. The adolescents completed the youth self-report
      measuring emotional and behavioural problems, and various questionnaires
      addressing life events, personality variables, perceived parental behaviour
      (PPB), family functioning, school environment, and social network. RESULTS:
      Adolescent migrants had significantly higher scores for internalizing and
      externalizing problems. There was a pattern of various unfavourable psychosocial
      features including life events, coping, self-related cognitions, and PPB that was
      more common among adolescent migrants than natives. Double-citizens were similar
      to natives in all domains. Young adolescents from South and South-East Europe
      differed from natives in terms of more unfavourable psychosocial features.
      Migrant status was best predicted by adverse psychosocial features rather than
      emotional and behavioural problems. CONCLUSION: There is some indication that
      certain migrant adolescents are at risk of psychosocial mal-adaptation.
      Obviously, ethnic origin is an important moderator.

PMID- 18818858
TI  - Socioeconomic status and anxiety as predictors of antidepressant treatment
      response and suicidal ideation in older adults.
AB  - BACKGROUND: Separate reports from the maintenance treatment for late-life
      depression (MTLD) trials have shown that low socioeconomic status (SES) and
      anxiety symptoms at the time of treatment initiation predict lower levels of
      response to antidepressant treatment and higher levels of suicidal ideation in
      older adults. AIM: To determine whether SES and anxiety independently contribute
      to worse treatment outcomes, as indicated by persistence of depressive symptoms
      during treatment and the persistence of suicidal ideation. Consistent with prior
      evidence that sociodemographic factors and clinical history are both prognostic
      of depression treatment efficacy, we hypothesized that SES and pre-existing
      anxiety symptoms will both predict lower levels of response to treatment and
      higher levels of suicidal ideation. METHOD: Secondary analyses of data from the
      MTLD trials. RESULTS: Regression analyses which controlled for comorbid anxiety
      indicated that residents of middle- and high-income census tracts were more
      likely to respond to treatment (HR, 1.63; 95%CI, 1.08-2.46) and less likely to
      report suicidal ideation during treatment (OR, 0.51; 95%CI, 0.28-0.90) than
      residents of low income census tracts. The same regression models indicated that
      pre-existing anxiety symptoms were independently related to lower treatment
      response (HR, 0.73; 95%CI, 0.60-0.89) and higher risk of suicidal ideation (OR,
      1.45; 95%CI, 0.98-2.14). CONCLUSION: These findings demonstrate the importance of
      treating anxiety symptoms during the course of treatment for late-life depression
      and, at the same time, addressing barriers to treatment response related to low
      SES.

PMID- 18818859
TI  - Intraspecific concerted evolution of the rDNA ITS1 in Anopheles farauti sensu
      stricto (Diptera: Culicidae) reveals recent patterns of population structure.
AB  - We examined the intraindividual variation present in the first ribosomal internal
      transcribed spacer (ITS1) of Anopheles farauti to determine the level of
      divergence among populations for this important malarial vector. We isolated 187
      clones from 70 individuals and found regional variation among four internal
      tandem repeats. The data were partitioned prior to analysis given the presence of
      a paralogous ITS2 sequence, called the 5'-subrepeat, inserted in the ITS1 of most
      clones. A high level of homogenization and population differentiation was
      observed for this repeat, which indicates a higher rate of turnover relative to
      the adjacent 'core' region. Bayesian analysis was performed using several
      substitutional models on both a combined and a partitioned data set. On the
      whole, the ITS1 phylogeny and geographic origin of the samples appear to be
      congruent. Some interesting exceptions indicate the spread of variant repeats
      between populations and the retention of ancestral polymorphism. Our data clearly
      demonstrate concerted evolution at the intraspecific level despite
      intraindividual variation and a complex internal repeat structure from a species
      that occupies a continuous coastal distribution. A high rate of genomic turnover
      in combination with a high level of sequence divergence appears to be a major
      factor leading to its concerted evolution within these populations.

PMID- 18818860
TI  - Divergence and polymorphism under the nearly neutral theory of molecular
      evolution.
AB  - The nearly neutral theory attributes most nucleotide substitution and
      polymorphism to genetic drift acting on weakly selected mutants, and assumes that
      the selection coefficients for these mutants are drawn from a continuous
      distribution. This means that parameter estimation can require numerical
      integration, and this can be computationally costly and inaccurate. Furthermore,
      the leading parameter dependencies of important quantities can be unclear, making
      results difficult to understand. For some commonly used distributions of mutant
      effects, we show how these problems can be avoided by writing equations in terms
      of special functions. Series expansion then allows for their rapid calculation
      and, also, illuminates leading parameter dependencies. For example, we show that
      if mutants are gamma distributed, the neutrality index is largely independent of
      the effective population size. However, we also show that such results are not
      robust to misspecification of the functional form of distribution. Some
      implications of these findings are then discussed.

PMID- 18818861
TI  - Application of COMPOCHIP microarray to investigate the bacterial communities of
      different composts.
AB  - A microarray spotted with 369 different 16S rRNA gene probes specific to
      microorganisms involved in the degradation process of organic waste during
      composting was developed. The microarray was tested with pure cultures, and of
      the 30,258 individual probe-target hybridization reactions performed, there were
      only 188 false positive (0.62%) and 22 false negative signals (0.07%). Labeled
      target DNA was prepared by polymerase chain reaction amplification of 16S rRNA
      genes using a Cy5-labeled universal bacterial forward primer and a universal
      reverse primer. The COMPOCHIP microarray was applied to three different compost
      types (green compost, manure mix compost, and anaerobic digestate compost) of
      different maturity (2, 8, and 16 weeks), and differences in the microorganisms in
      the three compost types and maturity stages were observed. Multivariate analysis
      showed that the bacterial composition of the three composts was different at the
      beginning of the composting process and became more similar upon maturation.
      Certain probes (targeting Sphingobacterium, Actinomyces,
      Xylella/Xanthomonas/Stenotrophomonas, Microbacterium, Verrucomicrobia,
      Planctomycetes, Low G + C and Alphaproteobacteria) were more influential in
      discriminating between different composts. Results from denaturing gradient gel
      electrophoresis supported those of microarray analysis. This study showed that
      the COMPOCHIP array is a suitable tool to study bacterial communities in
      composts.

PMID- 18818862
TI  - Glycaemic variability and inflammation in subjects with metabolic syndrome.
AB  - Subjects who develop diabetes have an increased cardiovascular risk even before
      the appearance of diabetes. The aim of this study was to investigate the
      glycaemic variability measured by continuous glucose monitoring (CGM CV%) in
      nondiabetic subjects with metabolic syndrome (MS) and to explore if glycaemic
      variability was associated with circulating levels of interleukin-6 (IL-6), a
      proinflammatory cytokine, or with an anti-inflammatory factor like adiponectin.
      Three groups of obese subjects with (MS+: 6m, 8f; BMI 33.1+/-1.4 mean+/-SEM) or
      without metabolic syndrome (MS-: 2m, 4f; BMI 29.2+/-2.2) and with MS associated
      with type 2 diabetes (MS/T2D: 3m, 5f; BMI 32.9+/-1.4) were investigated. The
      glycaemic variability was measured in all subjects in terms of CV% of the
      glycaemic values obtained every 3 min during the course of a 48 h CGM performed
      using a subcutaneous glucose sensor. The average CGM CV% increased from MS- group
      (21.1%) to the MS+ group (23.9%) and to the MS+/T2D group (27.4%) but it was not
      correlated to the CGM mean glycaemia (r=0.20; P=ns). In some instances, CGM CV%
      was found higher in MS+ subjects than in some MS+ T2D ones. Stepwise multiple
      correlation analysis showed that IL-6 predicted CGM CV% (R(2)=0.35, beta=0.13;
      P<0.05) independently from BMI, waist circumference, adiponectin and insulin
      concentrations. In conclusion, the CGM CV% may contribute to better describe the
      individual metabolic state and to understand the pathogenesis of endothelial
      dysfunction in non diabetic subjects with MS.

PMID- 18818863
TI  - Standards, guidelines and the practice of medicine.

PMID- 18818864
TI  - A longitudinal study of schizophrenia- and affective spectrum disorders in
      individuals diagnosed with a developmental language disorder as children.
AB  - The prevalence and types of schizophrenia- and affective spectrum disorders were
      studied in 469 individuals with a developmental language disorder (DLD), assessed
      in the same clinic during a period of 10 years, and 2,345 controls from the
      general population. All participants were screened through the nationwide Danish
      Psychiatric Central Register (DPCR). The mean length of follow-up was 34.7 years,
      and the mean age at follow-up 35.8 years. The results show an excess of
      schizophrenia spectrum disorders (F20-F29) within participants with DLD when
      compared with controls from the overall population (6.4% vs. 1.8%; P < 0.0001).
      For schizophrenia (F20.x) the respective figures were 3.8% versus 1.1%; P =
      0.0001. The variable degree of expressive language disorder was significantly
      associated with a schizophrenia spectrum disorder diagnosis in the DPCR. There
      was no significant increase in affective spectrum disorders (F30-F39) in the DLD
      case group (3.4% vs. 2.0%; P = 0.05). Our results provide additional support to
      the notion that DLD is a marker of increased vulnerability to the development of
      schizophrenia spectrum disorders.

PMID- 18818865
TI  - Novel HIV-1 long terminal repeat (LTR) sequences of subtype B and mosaic
      intersubtype B/C recombinants in North India.
AB  - Although the HIV-1 epidemic in India is mainly due to subtype C, other subtypes
      have also been reported from different parts of India. HIV-1 LTR sequence
      analysis from six HIV-1 infected individuals from North India was carried out to
      determine the nature and extent of variations. Four out of six samples formed a
      unique phylogenetic cluster which was close to subtype B. The other two samples
      (A3 and S3) turned out to be novel mosaic recombinants showing resemblance to
      subtypes B, B/C-India and B/C-Myanmar gene segments. All four subtype B LTR
      samples and the two B/C recombinants showed conserved as well as unique
      polymorphisms in all of the putative transcription factor binding sites (TFBS).
      These changes may potentially alter basal as well as Tat-mediated HIV-1 LTR
      promoter activation. The two recombinants possessed three copies of the NF-kappaB
      TFBS as seen with the majority of subtype C and recombinant B/C isolates reported
      earlier, but the other four non-recombinant B-LTRs showed only two copies of the
      NF-kappaB site. This is the first study to show a dominance of unique subtype B
      LTRs and strongly suggests that this region could also be a hot spot for the
      formation of highly complex inter subtype B/C recombinants.

PMID- 18818866
TI  - Development and use of genetic system to identify genes required for efficient
      low-temperature growth of Psychrobacter arcticus 273-4.
AB  - We describe the development of genetic tools (electroporation, conjugation,
      vector for targeted gene replacement) for use in the psychrophile Psychrobacter
      arcticus 273-4 to test hypotheses about cold adaptation. Successful
      electroporation only occurred with nonstandard parameters, such as:
      electrocompetent cells freshly prepared from stationary-phase cultures, high
      field strengths (25 kV cm(-1)), long recovery times (16-24 h), and selection with
      low concentrations of antibiotics. Transformation frequencies were greatly
      affected by a methylation-dependent restriction barrier homologous to DpnI. The
      vector pJK100 (which was self-transmissible and contained a Pir-dependent R6K
      origin of replication) proved effective as a suicide plasmid that could be used
      to recombine mutations into the P. arcticus 273-4 genome. We used this vector for
      targeted replacement of dctT, the substrate-binding periplasmic subunit of a TRAP
      (tripartite ATP-independent periplasmic) transporter (which we have named
      dctTUF), as it was more highly expressed at cold temperatures. The replacement of
      dctT (with kan) decreased the rate of growth at low temperatures in mineral
      medium with glutamate, acetate, butyrate, and fumarate, but not with pyruvate
      suggesting that DctTUF participates in the transport of glutamate, acetate,
      butyrate, and fumarate at cold temperatures. This is the first report to
      demonstrate the creation of site-specific mutants in the genus Psychrobacter,
      their affect on low-temperature growth, and a substrate range for TAXI proteins
      of TRAP transporters.

PMID- 18818867
TI  - The stability of the archaeal HU histone-like DNA-binding protein from
      Thermoplasma volcanium.
AB  - The complete genome analysis of the archaeon Thermoplasma volcanium has revealed
      a gene assigned to encode the histone-like DNA-binding protein HU. Thermoplasma
      volcanium is a moderate thermophile growing around 60 degrees C and it is
      adaptable to aerobic and anaerobic environment and therefore it is unique as a
      candidate for the origin of eukaryotic nuclei in the endosymbiosis hypothesis.
      The HU protein is the major component of the bacterial nuclei and therefore it is
      an important protein to be studied. The gene for HUTvo protein (huptvo) was
      cloned from the genomic DNA of T. volcanium and overexpressed in Escherichia
      coli. A fast and efficient purification scheme was established to produce an
      adequate amount of bioactive protein for biochemical and biophysical studies.
      Highly purified HUTvo was studied for its DNA-binding activity and
      thermostability. As studied by circular dichroism and high-precision differential
      scanning microcalorimetry, the thermal unfolding of HUTvo protein is reversible
      and can be well described by a two-state model with dissociation of the native
      dimeric state into denatured monomers. The G versus T profile for HUTvo compared
      to the hyperthermophilic marine eubacterial counterpart from Thermotoga maritima,
      HUTmar, clearly shows that the archaeal protein has adopted a less efficient
      molecular mechanism to cope with high temperature. The molecular basis of this
      phenomenon is discussed.

PMID- 18818868
TI  - Miller-Fisher syndrome in a patient with rheumatoid arthritis treated with
      adalimumab.
AB  - Adalimumab is a frequently prescribed TNFalpha inhibitor for treatment of
      rheumatoid arthritis. We report on a patient who probably developed a Miller
      Fisher syndrome after the second injection of adalimumab.

PMID- 18818870
TI  - Biology and evolution of the endogenous koala retrovirus.
AB  - Although endogenous retroviruses are ubiquitous features of all mammalian
      genomes, the process of initial germ line invasion and subsequent inactivation
      from a pathogenic element has not yet been observed in a wild species. Koala
      retrovirus (KoRV) provides a unique opportunity to study this process of
      endogenisation in action as it still appears to be spreading through the koala
      population. Ongoing expression of the endogenous sequence and consequent high
      levels of viraemia have been linked to neoplasia and immunosuppression in koalas.
      This apparently recent invader of the koala genome shares a remarkably close
      sequence relationship with the pathogenic exogenous Gibbon ape leukaemia virus
      (GALV), and comparative analyses of KoRV and GALVare helping to shed light on how
      retroviruses in general adapt to a relatively benign or at least less pathogenic
      existence within a new host genome. (Part of a multi-author review).

PMID- 18818869
TI  - Coevolution of endogenous betaretroviruses of sheep and their host.
AB  - Sheep betaretroviruses offer a unique model system to study the complex
      interaction between retroviruses and their host. Jaagsiekte sheep retrovirus
      (JSRV) is a pathogenic exogenous retrovirus and the causative agent of ovine
      pulmonary adenocarcinoma. The sheep genome contains at least 27 copies of
      endogenous retroviruses (enJSRVs) highly related to JSRV. enJSRVs have played
      several roles in the evolution of the domestic sheep as they are able to block
      the JSRV replication cycle and play a critical role in sheep conceptus
      development and placental morphogenesis. Available data strongly suggest that
      some dominant negative enJSRV proviruses (i.e. able to block JSRV replication)
      have been positively selected during evolution. Interestingly, viruses escaping
      the transdominant enJSRV loci have recently emerged (less than 200 years ago).
      Thus, endogenization of these retroviruses may still be occurring today.
      Therefore, sheep provide an exciting and unique system to study retrovirus-host
      coevolution. (Part of a multi-author review).

PMID- 18818871
TI  - Porcine endogenous retroviruses and xenotransplantation.
AB  - Xenotransplantation is defined by the PHS as any procedure that involves the
      transplantation, implantation or infusion into a human recipient of either (a)
      live cells, tissues or organs from a nonhuman animal source, or (b) human body
      fluids, cells, tissues or organs that have had ex vivo contact with live nonhuman
      animal cells, tissues or organs (Public Health Service Guideline on Infectious
      Disease Issues in Xenotransplantation). Use of pigs for human xenotransplantation
      raises concerns about the risks of transfer of infectious agents from the pig
      cells to xenotransplantation recipients. The observation that the porcine
      germline harbors genetic loci encoding porcine endogenous retroviruses (PERVs)
      that are in some cases infectious for human cells has resulted in renewed
      scientific interest in PERVs. However, in spite of the past 10 years of
      investigation, the actual risk for PERV infection, replication, and pathogenic
      outcome in human recipients of xenotransplantation products is still undefined.
      (Part of a multi-author review).

PMID- 18818873
TI  - Endogenous retroviruses and cancer.
AB  - The genomes of vertebrates contain sequences that are similar to present-day
      exogenous retroviruses. Such sequences, called endogenous retroviruses (ERVs),
      have resulted from ancestral germ line infections by exogenous retroviruses which
      have thereafter been transmitted in a Mendelian fashion. By analogy to exogenous
      tumorigenic retroviruses, ERVs have been implicated in the pathogenesis of
      cancer. Cumulative evidence from animal models indicates that ERVs may
      participate in the process of malignant transformation or promote tumor growth,
      e.g. through insertional mutagenesis or via counteracting tumor
      immunosurveillance. Here, we review the role of ERVs in tumorigenesis with focus
      on human ERVs (HERVs) in human cancer. Although available data suggest a
      potential role of HERVs in human cancers, in particular germ cell tumors, the
      contributions of HERVs to human tumorigenesis warrant further elucidation. (Part
      of a multi-author review).

PMID- 18818874
TI  - Evolution of human endogenous retroviral sequences: a conceptual account.
AB  - Endogenous retroviruses (ERVs) most likely are remnants of ancient retroviral
      infections. ERVs preserve functions of exogenous retroviruses to a varying
      extent, and can be parasites, symbionts or more or less neutral genetic
      'junk'.Their evolution has two facets, pre- and post-endogenization. Although the
      two are not clearly separated, the first pertains to retroviral evolution in
      general and the second to the fate of repetitive DNA and the evolution of the
      host organism and its genome. The study of ERVs provides much material for the
      understanding of retroviral evolution. This sequence archive reflects the history
      of successes and shortcomings of antiviral resistance, but also of strategic
      evolutionary decisions regarding genome organization and new gene acquisition.
      This review discusses retroviral evolution illustrated through HERVs,
      bioinformatic prerequisites for ERV studies, the endogenization process and HERV
      evolution post-endogenization, including relation to disease. (Part of a multi
      author review).

PMID- 18818875
TI  - Keeping active endogenous retroviral-like elements in check: the epigenetic
      perspective.
AB  - Endogenous retrovirus-like elements, or ERVs, are an abundant component of all
      eukaryotic genomes. Their transcriptional and retrotranspositional activities
      have great potential for deleterious effects on gene expression. Consequences of
      such activity may include germline mutagenesis and cancerous transformation. As a
      result, mammalian genomes have evolved means of counteracting ERV transcription
      and mobilization. In this review, we discuss epigenetic mechanisms of ERV and LTR
      retrotransposon control during mouse development, focusing on involvement of DNA
      methylation, histone modifications, small RNAs and their interaction with one
      another. We also address relevance of research performed in the mouse system to
      human and challenges associated with studying repetitive families. (Part of a
      multi-author review).

PMID- 18818872
TI  - Murine endogenous retroviruses.
AB  - Up to 10% of the mouse genome is comprised of endogenous retrovirus (ERV)
      sequences, and most represent the remains of ancient germ line infections. Our
      knowledge of the three distinct classes of ERVs is inversely correlated with
      their copy number, and their characterization has benefited from the availability
      of divergent wild mouse species and subspecies, and from ongoing analysis of the
      Mus genome sequence. In contrast to human ERVs, which are nearly all extinct,
      active mouse ERVs can still be found in all three ERV classes. The distribution
      and diversity of ERVs has been shaped by host-virus interactions over the course
      of evolution, but ERVs have also been pivotal in shaping the mouse genome by
      altering host genes through insertional mutagenesis, by adding novel regulatory
      and coding sequences, and by their co-option by host cells as retroviral
      resistance genes. We review mechanisms by which an adaptive coexistence has
      evolved. (Part of a multi-author review).

PMID- 18818876
TI  - Endogenous retroviruses--aiding and abetting genomic plasticity.

PMID- 18818877
TI  - On the mechanism of inhibition of p27 degradation by 15-deoxy-Delta12,14
      prostaglandin J2 in lymphoblasts of Alzheimer's disease patients.
AB  - It has been proposed that neuroinflammation, among other factors, may trigger an
      aberrant neuronal cell cycle re-entry leading to neuronal death. Cell cycle
      disturbances are also detectable in peripheral cells from Alzheimer's disease
      (AD) patients. We previously reported that the anti-inflammatory 15- deoxy
      Delta(12,14)-prostaglandin J (2) (15d-PGJ (2)) increased the cellular content of
      the cyclin-dependent kinase inhibitor p27, in lymphoblasts from AD patients. This
      work aimed at elucidating the mechanisms of 15d-PGJ (2)-induced p27 accumulation.
      Phosphorylation, half-life, and the nucleo-cytoplasmic traffic of p27 protein
      were altered by 15d-PGJ2 by mechanisms dependent on PI3K/Akt activity. 15d-PGJ
      (2) prevents the calmodulin-dependent Akt overactivation in AD lymphoblasts by
      blocking its binding to the 85-kDa regulatory subunit of PI3K. These effects of
      15d-PGJ (2) were not mimicked by 9,10-dihydro-15-deoxy-Delta(12,14)-
      prostaglandin J (2), suggesting that 15d-PGJ (2) acts independently of peroxisome
      proliferator-activated receptor gamma activation and that the alpha,beta
      unsaturated carbonyl group in the cyclopentenone ring of 15d-PGJ (2) is a
      requisite for the observed effects.

PMID- 18818878
TI  - Structural insights into the multiple functions of protein C inhibitor.
AB  - Protein C inhibitor (PCI) is a widely distributed, multifunctional member of the
      serpin family of protease inhibitors, and has been implicated in several
      physiological processes and disease states. Its inhibitory activity and
      specificity are regulated by binding to cofactors such as heparin, thrombomodulin
      and phospholipids, and it also appears to have non-inhibitory functions related
      to hormone and lipid binding. Just how the highly conserved serpin architecture
      can support the multiple diverse functions of PCI is a riddle best addressed by
      protein crystallography. Over the last few years we have solved the structure of
      PCI in its native, cleaved and protein-complexed states. They reveal a conserved
      serpin fold and general mechanism of protease inhibition, but with some unique
      features relating to inhibitory specificity/promiscuity, cofactor binding and
      hydrophobic ligand transport.

PMID- 18818879
TI  - Ikaros negatively regulates inducible nitric oxide synthase expression in
      macrophages: involvement of Ikaros phosphorylation by casein kinase 2.
AB  - Ikaros is known as a critical regulator of lymphocyte development. We examined
      the regulatory role of Ikaros in LPS/IFN-gamma-induced inducible nitric oxide
      synthase (iNOS) expression by macrophages. Our results showed that IK6 (Ikaros
      dominant negative isoform) induction increases the iNOS expression. Ikaros DNA
      binding activity on the iNOS promoter was decreased, and a mutation of the Ikaros
      binding site on the iNOS promoter resulted in an increase in LPS/IFN-gamma
      induced iNOS expression. LPS/IFN-gamma increased the histone (H3) acetylation on
      the Ikaros DNA binding site. These results suggest that Ikaros acts as a negative
      regulator on iNOS expression. Treatment with a casein kinase 2 (CK2) inhibitor
      reversed LPS/IFN-gamma-induced decrease in Ikaros DNA binding activity. Moreover,
      overexpression of kinase-inactive CK2 decreased iNOS expression and a significant
      amount of CK2alpha1 translocated into the nucleus in LPS/IFN-gamma-treated cells.
      Overall, these data indicate that LPS/IFN-gamma decreases the Ikaros DNA binding
      activity via the CK2 pathway, resulting in an increase of iNOS expression.

PMID- 18818880
TI  - Bone marrow transplantation for severe aplastic anemia secondary to temozolomide.
AB  - Radiotherapy (RT) and concomitant/adjuvant therapy with temozolomide (Temodar) is
      a common treatment regimen for children and adults with glioma. Although
      temozolomide is generally well tolerated with temporary myelosuppression as the
      primary dose-limiting toxicity, irreversible bone-marrow aplasia after treatment
      with temozolomide has been reported. We report the case of an adolescent patient
      with a high-grade glioma who, after >2 years of event-free survival, underwent
      successful bone marrow transplantation for treatment of temozolomide-induced
      severe aplastic anemia (SAA).

PMID- 18818881
TI  - Intracoronary pharmacotherapy in the management of coronary microvascular
      dysfunction.
AB  - Although percutaneous coronary intervention restores optimal epicardial blood
      flow in most cases, abnormal myocardial perfusion may still persist. This might
      be as a result of macro and microembolization, neutrophil plugging,
      vasoconstriction, myocyte contracture, local intracellular and interstitial
      edema, intramural haemorrhage, and endothelial blistering. Local delivery of
      intracoronary pharmacotherapy via the coronary arteries may increase local drug
      concentration several fold, and may improve drug efficacy. Several
      pharmacological agents such as adenosine, calcium channel blockers, alpha
      blockers, beta2 receptor activators, vasodilators, antithrombotics, and
      antiplatelet agents have been used to treat coronary microvascular dysfunction.
      This article reviews the results of trials of intracoronary pharmacotherapy to
      date.

PMID- 18818882
TI  - Parameterization of an empirical model for the prediction of n-octanol, alkane
      and cyclohexane/water as well as brain/blood partition coefficients.
AB  - Quantitative information of solvation and transfer free energies is often needed
      for the understanding of many physicochemical processes, e.g the molecular
      recognition phenomena, the transport and diffusion processes through biological
      membranes and the tertiary structure of proteins. Recently, a concept for the
      localization and quantification of hydrophobicity has been introduced (Jager et
      al. J Chem Inf Comput Sci 43:237-247, 2003). This model is based on the
      assumptions that the overall hydrophobicity can be obtained as a superposition of
      fragment contributions. To date, all predictive models for the logP have been
      parameterized for n-octanol/water (logP(oct)) solvent while very few models with
      poor predictive abilities are available for other solvents. In this work, we
      propose a parameterization of an empirical model for n-octanol/water,
      alkane/water (logP(alk)) and cyclohexane/water (logP(cyc)) systems. Comparison of
      both logP(alk) and logP(cyc) with the logarithms of brain/blood ratios (logBB)
      for a set of structurally diverse compounds revealed a high correlation showing
      their superiority over the logP(oct) measure in this context.

PMID- 18818883
TI  - The technological transformation of patient-driven human immunology research.
AB  - New scientific technologies applied to patients with rare diseases are
      facilitating discoveries about how the human immune system is regulated at the
      molecular level. Studies of patients with autoimmune lymphoproliferative syndrome
      (ALPS) or caspase-8 deficiency state (CEDS) demonstrated the ability of gene
      expression microarray analyses and small interfering RNAs (siRNA) to establish
      the physiologically important roles of NRAS, caspase-10, and caspase-8 for normal
      lymphocyte apoptosis and activation. The advent of genomics technologies such as
      next generation sequencing will complement these and more traditional approaches.
      These advances are anticipated to accelerate the pace of new discoveries in
      patients with immunological disorders.

PMID- 18818884
TI  - Innate immunity in the pathogenesis of polytropic retrovirus infection in the
      central nervous system.
AB  - Neuroinflammation, including astrogliosis, microgliosis, and the production of
      proinflammatory cytokines and chemokines is a common response in the central
      nervous system (CNS) to virus infection, including retrovirus infection. However,
      the contribution of this innate immune response in disease pathogenesis remains
      unresolved. Analysis of the neuroinflammatory response to polytropic retrovirus
      infection in the mouse has provided insight into the potential contribution of
      the innate immune response to retrovirus-induced neurologic disease. In this
      model, retroviral pathogenesis correlates with the induction of neuroinflammatory
      responses including the activation of astrocytes and microglia, as well as the
      production of proinflammatory cytokines and chemokines. Studies of the
      neurovirulent determinants of the polytropic envelope protein as well as studies
      with knockout mice suggest that retroviral pathogenesis in the brain is
      multifaceted and that cytokine and chemokine production may be only one mechanism
      of disease pathogenesis. Analysis of the activation of the innate immune response
      to retrovirus infection in the CNS indicates that toll-like receptor 7 (TLR7) is
      a contributing factor to retrovirus-induced neuroinflammation, but that other
      factors can compensate for the lack of TLR7 in inducing both neuroinflammation
      and neurologic disease.

PMID- 18818885
TI  - Eosinophils and their interactions with respiratory virus pathogens.
AB  - Eosinophils are implicated in the pathophysiology of respiratory virus infection,
      most typically in negative roles, such as promoting wheezing and
      bronchoconstriction in conjunction with virus-induced exacerbations of reactive
      airways disease and in association with aberrant hypersensitivity responses to
      viral vaccines. However, experiments carried out in vitro and in vivo suggest
      positive roles for eosinophils, as they have been shown to reduce virus
      infectivity in tissue culture and promote clearance of the human pathogen,
      respiratory syncytial virus in a mouse challenge model. The related natural
      rodent pathogen, pneumonia virus of mice (PVM), is highly virulent in mice, and
      is not readily cleared by eosinophils in vivo. Interestingly, PVM replicates in
      eosinophils and promotes cytokine release. The molecular basis of virus infection
      in eosinophils and its relationship to disease outcome is currently under study.

PMID- 18818886
TI  - Transcriptional regulation of early B cell development.
AB  - All blood cell types including mature B cells derive from pluripotent
      hematopoietic stem cells. The developmental cues responsible for guiding
      multipotent cells to the B cell fate remain to be fully elucidated. During recent
      years, it has become clear that firm commitment to the B cell fate requires the
      active suppression of differentiation potentials for alternative fates. Through
      the work of our laboratory and many others, it is now apparent that early B cell
      development and B-lineage commitment is controlled by a complex interplay between
      specific cytokine receptors and a variety of transcription factors. Whereas the
      transcription factor Pax5 has been touted as the chief transcriptional regulator
      of B-lineage commitment, our recent studies suggest that the B cell fate is
      established through the concerted action of several transcription factors
      including Early B cell Factor-1 (EBF). Notably, we recently found that EBF is
      able to suppress myeloid and T cell differentiation when introduced into
      multipotent Pax5(null/null) progenitors. Past work has also established that EBF
      expression is connected to the activity of the receptor for the cytokine IL-7.
      Therefore, the IL-7/EBF pathway plays a key and non-redundant role in
      establishing the B cell fate. This work provides a provisional model for
      understanding the molecular basis for B cell developmental biology. Furthermore,
      because aging leads to a decline in early B cell development and reduced IL-7
      responsiveness, this work establishes a conceptual framework for understanding
      how and why aging leads to the loss of early B cell precursors.

PMID- 18818887
TI  - Perioperative use of recombinant factor VII to prevent intraoperative aneurysm
      rupture in high risk patients: a preliminary safety evaluation.
AB  - OBJECT: The authors present a safety evaluation of the perioperative use of
      recombinant activated factor VII (rFVIIa) in a series of subarachnoid hemorrhage
      patients undergoing microsurgical aneurysm clipping. METHODS: We performed a
      retrospective chart review of the records of 18 consecutive subarachnoid
      hemorrhage patients who underwent craniotomy for aneurysm clipping and received
      an intraoperative dose of rFVIIa. In each case, the aneurysm was felt to be a
      "high risk" lesion for intraoperative rupture either because it had bled multiple
      times prior to surgery or based on anatomical considerations. All complications
      were recorded whether or not they were attributed to the use of rFVIIa. RESULTS:
      Eighteen patients, 7 men and 11 women, ranging in age from 42 to 85 years were
      included in this review. Nine patients (50%) were either Hunt/Hess Grades IV or
      V. Six patients developed clinically significant cerebral vasospasm. Fifteen
      patients required ventricular drainage on admission, and seven patients
      ultimately required a ventriculoperitoneal shunt. One lower extremity deep venous
      thrombosis and seven upper extremity venous thromboses in association with
      peripherally inserted central catheter (PICC) lines were identified on screening
      Doppler evaluations. There were no associated pulmonary emboli. No aneurysm
      ruptured intraoperatively. CONCLUSION: We describe our experience with the use of
      a single dose of rFVIIa administered perioperatively in an attempt to decrease
      the rate of intraoperative aneurysm rupture in patients undergoing microsurgical
      aneurysm clipping. There were no significant immediate or long-term adverse
      effects attributable to the use of rFVIIa in this group, and we encountered no
      intraoperative ruptures in this relatively small series.

PMID- 18818888
TI  - Does brain swelling increase estimated specific gravity?
AB  - OBJECTIVE: At the acute phase of traumatic brain injury (TBI), brain swelling
      contributes substantially to the development of secondary neurological lesions.
      Elucidating the pathophysiology of brain swelling is crucial to improve TBI
      management. In a previous study, specific gravity (SG) of the noncontused
      hemisphere, as estimated by computed tomography (CT), was higher in patients with
      high Marshall CT scores and severe brain swelling. The aim of this study was to
      investigate the relationship between estimated specific gravity (eSG) and
      clinical variable suggestive of brain swelling. DESIGN: Retrospective study of
      data from a prospectively established database. SETTING: Neurology ICU in a
      teaching hospital in Paris, France. PARTICIPANTS: We studied 20 patients with
      severe traumatic brain injury (TBI), 20 patients with high-grade subarachnoid
      hemorrhage (SAH) presenting similar brain-swelling criteria, 20 patients with low
      grade SAH, and 20 healthy controls. INTERVENTIONS: None. MEASUREMENTS AND
      RESULTS: Estimated brain specific gravity was acquired from CT images obtained at
      ICU admission. eSG was estimated in the overall intracerebral content and in a
      region-of-interest composed of white matter and the diencephalon. eSG in the
      region of interest was significantly higher in the TBI patients than in the high
      grade SAH patients (1.0350 +/- 0.0041 vs. 1.0310 +/- 0.0019 g/ml, P < 0.05). eSG
      was similar in the high-grade SAH, low-grade SAH, and control groups.
      CONCLUSIONS: Our findings do not support a causal link between brain swelling and
      eSG elevation. The eSG increase in severe TBI patients is not due to brain
      swelling.

PMID- 18818889
TI  - Cost saving measures for low birth weight babies nutrition in resource poor
      nations.

PMID- 18818890
TI  - HIV disease presenting as a unilateral parotid gland swelling.

PMID- 18818891
TI  - [Resuscitation of newborn infants].
AB  - Although almost 10% of all newborn infants need some form of respiratory
      assistance after birth, only 1% will require more advanced forms of
      resuscitation. Because these rare events cannot always be anticipated,
      pediatricians and neonatologists may not be readily available and resuscitation
      will have to be performed by anesthesiologists. In recent years, international
      guidelines for neonatal resuscitation have been revised by the International
      Liaison Committee on Resuscitation (ILCOR), the American Academy of Pediatrics
      (AAP) and the American Heart Association (AHA), as well as the European
      Resuscitation Council (ERC). The revised guidelines describe a simplified
      resuscitation algorithm which emphasizes the central role of respiratory support
      and an increase in heart rate is judged to be the best marker for successful
      ventilation. In deliveries complicated by meconium-stained amniotic fluid,
      intrapartum suctioning of the oropharynx is no longer recommended and
      endotracheal suctioning is restricted to severely depressed babies. The new
      guidelines mention the use of the laryngeal mask airway (LMA) and CO(2) detectors
      without, however, making firm recommendations. The use of 100% oxygen in neonatal
      resuscitation is increasingly being challenged. In the rare event of a newborn
      whose heart rate drops below 60 beats/min, more advanced resuscitation (chest
      compressions using the 2-thumb-encircling-hands technique, epinephrine 10-30
      mug/kgBW i.v.) will be required. Finally, the guidelines mention the possible
      neuroprotective effect of therapeutic hypothermia after asphyxia, but finally
      only recommend that hyperthermia should be avoided.

PMID- 18818892
TI  - [Hereditary carcinoma. It's all in the genes!].

PMID- 18818893
TI  - [Hereditary pancreatic cancer].
AB  - An inherited predisposition to pancreatic cancer (PC) is prevalent in about 3% of
      PC cases and is currently believed to occur in three distinct clinical settings,
      (1) hereditary tumour predisposition syndromes with an increased risk of PC such
      as Peutz-Jeghers syndrome and familial atypical multiple mole melanoma, (2)
      hereditary pancreatitis and cystic fibrosis, in which genetically determined
      early-age changes of the pancreas can predispose to the development of PC, and
      (3) familial pancreatic cancer syndrome (FPC). According to a recent consensus
      conference, high-risk individuals from PC-prone families should be enrolled in
      board-approved, prospective, controlled screening programs at expert centres.
      Based on the available data, prophylactic pancreatectomy is not indicated, since
      the underlying causative gene defect of the FPC syndrome is still unknown and the
      penetrance of PC in other tumour predisposition syndromes is either low or yet
      undetermined. In case of the diagnosis of a PC or high-grade precursor lesions, a
      prophylactic extension of the resection can be considered, since patients with
      hereditary PC often develop multifocal pancreatic lesions.

PMID- 18818894
TI  - [Hereditary thyroid cancer].
AB  - Hereditary thyroid carcinomas are present in about 5% of differentiated (DTC) and
      25% of medullary thyroid carcinomas (MTC). They are part of a multiorgan tumour
      syndrome (e. g. FAP Gardner's syndrome with DTC and MEN 2 syndrome with MTC) or
      confined to the thyroid gland. Hereditary thyroid carcinomas typically show
      multifocal growth and occur in young patients. Due to germ cell mutations as the
      underlying cause of disease, partial thyroidectomies that may be justified in
      early sporadic carcinomas are not indicated in this type of tumours. In the case
      of hereditary DTC, the genetic basis of the disease has been demonstrated only in
      syndromatic tumour variants. In most nonsyndromatic cases, specific genetic
      alterations have not yet been identified. In both types of hereditary DTC,
      prophylactic thyroidectomy is not warranted due to the favourable prognosis of
      tumours that do not differ from sporadic ones. Point mutations of the RET proto
      oncogene have been known for 15 years to be the genetic basis of hereditary MTC.
      Recently several new mutations were discovered; however, final conclusions
      regarding their clinical significance are not possible at present. Basically it
      has been shown that the clinical aggressivity of tumour development follows a
      genotype-phenotype correlation (risk groups 1-3). However, in mutations of all
      risk classes there exists a wide spectrum of different stages of hereditary C
      cell disease in individual risk groups. Regarding time and extent of prophylactic
      thyroidectomy (without or with lymph node dissection) a combined molecular
      biochemical concept including the use of pentagastrin-stimulated calcitonin
      values is therefore recommended.

PMID- 18818895
TI  - [Current short- and long-term results of lumbar disc replacement : update 2008].
AB  - Lumbar total disc replacement is an increasingly common way of treating
      degenerative lumbar disc disease while preserving mobility. The aim of this
      analysis was to survey evidence-based data to classify the procedure. Based on a
      MEDLINE inquiry, 38 clinical trials dealing with lumbar total disc replacement
      were selected and analyzed by the criteria of indication, preoperative procedure,
      and clinical follow-up. These data represent 3,180 patient-related evaluations
      with follow-up of 5.9 to 204 months. We also included ten retrospective studies.
      Patient satisfaction was a mean of 90.73%, and the Oswestry Disability Index and
      Visual Analog Scale were significantly lower. High rates of revision surgery,
      explantation surgery, and secondary fusions are linked to wrong preoperative
      indication. According to evidence criteria, the results show that lumbar total
      disc replacement is a safe procedure with a high rate of success. There is clear
      evidence that both imprecise indication and the choice of too-small implants
      significantly reduce the prospect of surgical success and increase the rates of
      reintervention.

PMID- 18818896
TI  - [Qualitative and quantitative analysis of urolithiasis with the Rietveld method
      (x-ray diffraction)].
AB  - BACKGROUND: The Rietveld method is one of the most innovative and most important
      applications in x-ray diffraction and has now, for the first time, been applied
      to standard-free precise quantitative crystallographic analysis of urinary
      stones. MATERIAL AND METHODS: The capability of the Rietveld method was
      demonstrated by analysis of a synthetic mixture of five typical urinary stones:
      whewellite, hydroxylapatite, brushite, struvite, and uric acid, with 20 weight %
      for each pure component. RESULTS: The quantitative phase analysis (Rietveld
      method) yielded a mean absolute error of only 1.6% for the weight fractions of
      the single urinary stone components. The largest error in weight fraction, 2.3%,
      occurred with hydroxylapatite, caused by the typical insufficient crystallinity.
      CONCLUSION: Crystallographic analysis of complex urinary stones with the aid of x
      ray diffraction, in combination with a Rietveld structure refinement, is the
      method of first choice for qualitative and quantitative phase analysis. With this
      tool, significant changes in weight fractions for recurrent urinary stones can be
      precisely detected, with therapeutic consequences.

PMID- 18818897
TI  - Quantitative trait loci for carbon isotope discrimination are repeatable across
      environments and wheat mapping populations.
AB  - Wheat productivity is commonly limited by a lack of water essential for growth.
      Carbon isotope discrimination (Delta), through its negative relationship with
      transpiration efficiency, has been used in selection of higher wheat yields in
      breeding for rainfed environments. The potential also exists for selection of
      increased Delta for improved adaptation to irrigated and high rainfall
      environments. Selection efficiency of Delta would be enhanced with a better
      understanding of its genetic control. Three wheat mapping populations
      (Cranbrook/Halberd, Sunco/Tasman and CD87/Katepwa) containing between 161 and 190
      F(1)-derived, doubled-haploid progeny were phenotyped for Delta and agronomic
      traits in 3-5 well-watered environments. The range for Delta was large among
      progeny (c. 1.2-2.3 per thousand), contributing to moderate-to-high single
      environment (h (2) = 0.37-0.91) and line-mean (0.63-0.86) heritabilities.
      Transgressive segregation was large and genetic control complex with between 9
      and 13 Delta quantitative trait loci (QTL) identified in each cross. The Delta
      QTL effects were commonly small, accounting for a modest 1-10% of the total
      additive genetic variance, while a number of chromosomal regions appeared in two
      or more populations (e.g. 1BL, 2BS, 3BS, 4AS, 4BS, 5AS, 7AS and 7BS). Some of the
      Delta genomic regions were associated with variation in heading date (e.g. 2DS,
      4AS and 7AL) and/or plant height (e.g. 1BL, 4BS and 4DS) to confound genotypic
      associations between Delta and grain yield. As a group, high Delta progeny were
      significantly (P < 0.10-0.01) taller and flowered earlier but produced more
      biomass and grain yield in favorable environments. After removing the effect of
      height and heading date, strong genotypic correlations were observed for Delta
      and both yield and biomass across populations (r (g) = 0.29-0.57, P < 0.05) as
      might be expected for the favorable experimental conditions. Thus selection for
      Delta appears beneficial in increasing grain yield and biomass in favorable
      environments. However, care must be taken to avoid confounding genotypic
      differences in Delta with stature and development time when selecting for
      improved biomass and yield especially in environments experiencing terminal
      droughts. Polygenic control and small size of individual QTL for Delta may reduce
      the potential for QTL in marker-assisted selection for improved yield of wheat.

PMID- 18818898
TI  - Construction of SSR-based chromosome map in bunching onion (Allium fistulosum).
AB  - We have constructed a linkage map of bunching onion (Allium fistulosum L., 2n =
      16) using an F(2) population of 225 plants. The map consists of 17 linkage groups
      with 212 bunching onion SSR markers and 42 bulb onion (A. cepa L.) SSR, InDel,
      CAPS or dCAPS markers, covering 2,069 cM. This is the first report of a linkage
      map mainly based on SSR markers in the genus Allium. With the 103 anchor markers
      [81 bunching onion SSRs, 11 bulb onion SSRs and 11 bulb onion non-SSRs (1 InDel,
      9 CAPSs and 1 dCAPS)] whose chromosome assignments were identified in A. cepa
      and/or A. fistulosum, via the use of several kinds of Allium alien addition
      lines, 16 of the 17 linkage groups were connected to the 8 basic chromosomes of
      A. cepa.

PMID- 18818899
TI  - Pm23: a new allele of Pm4 located on chromosome 2AL in wheat.
AB  - Powdery mildew, caused by Blumeria graminis f. sp. tritici, is one of the major
      diseases of common wheat (Triticum aestivum) worldwide. The powdery mildew
      resistance gene Pm23, identified in the common wheat Line 81-7241 and originally
      assigned to wheat chromosome 5A, was relocated on chromosome 2AL with the aid of
      molecular markers. Mapping of microsatellite markers in two wheat crosses
      segregating for Pm23 and Pm4b, respectively, in combination with the reported
      mapping of Pm4a, indicated that the three genes were all linked to the marker
      Xgwm356 with a distance of 3-5 cM. Allelism between Pm4b and Pm23 was then
      confirmed, when the progenies of a cross between VPM1 (Pm4b) and Line 81-7241,
      were shown to be all resistant to a B. graminis isolate avirulent to the both
      parents. Pm23 is therefore a new allele of the Pm4 locus, and was redesignated as
      Pm4c.

PMID- 18818900
TI  - Arthroscopic repair of isolated type II superior labrum anterior-posterior
      lesion.
AB  - The effectiveness of arthroscopic repair of type II superior labrum anterior
      posterior lesion (SLAP) was unclear as previous studies examined this treatment
      with patients of combined types of SLAP lesions. To address this research gap, we
      evaluated the clinical and functional outcomes of arthroscopic repair for 16
      patients (mean=24.2, SD=6.5) with clinical evidence of isolated type II SLAP
      lesion. After having arthroscopic stabilizations with Bioknotless suture anchors
      (Mitek), the patients were offered post-operative rehabilitation programs (e.g.,
      physiotherapy) for 6 months. The symptoms of SLAP lesion and the functions of the
      shoulder were assessed pre-operatively and 28-month post-operatively by O'Brien
      test, Speed test, Yergason test, and University of California at Los Angeles
      rating for pain and function of the shoulder. Wilcoxon Signed Ranks test and
      McNemar test were employed to analyze the difference between assessment in pre
      operation and post-operation phases. The result showed that patients' shoulder
      functions improved (UCLA Shoulder Score), and symptoms of SLAP lesion reduced
      (O'Brien test, Speed test, and Yergason test) significantly (P<0.05). Time for
      returning to play with pre-injury level was in average 9.4 months (range 4-24),
      and no complication or recurrence was detected. We concluded that arthroscopic
      repair is an effective operation of type II SLAP lesion with good clinical and
      functional outcomes; however, athletes with high demand of overhead throwing
      activities are likely to take longer duration of rehabilitation to attain full
      recovery.

PMID- 18818901
TI  - Magnetic resonance imagination of the peroneus longus tendon after anterior
      cruciate ligament reconstruction.
AB  - Several studies report that tendons can regenerate after harvesting. These
      studies have been performed especially in patellar and hamstring tendons. At our
      institution, 10 cm length of full thickness peroneus longus tendon has been
      harvested to reconstruct torn anterior cruciate ligament since 1997 as a
      different graft source. The aim of this study was to investigate whether the
      peroneus longus tendon used the anterior cruciate ligament reconstruction has a
      regeneration potential or not. Twelve patients, who had originally undergone
      harvesting of the peroneus longus tendon for the primary surgery of the anterior
      cruciate ligament reconstruction, underwent magnetic resonance imaging (MRI).
      Images of both legs were acquired simultaneously with the use of the scanner's
      extremity coil, as we aimed to compare harvested peroneus longus tendon with the
      other leg's peroneus longus tendon (healthy side) for evaluation of the
      regeneration potential. The average age of the patients was 31 years. There were
      eight right and four left legs. The average time interval was 52 months between
      ligament surgery and MRI. In all patients, a varying amount of the regeneration
      of the peroneus longus tendon was seen on the MRI images. Although the extent of
      PLT regeneration in proximal sections seemed better than in mid- and distal
      sections, there was no statistical difference between sections (P = 0.130). These
      data show that the peroneus longus tendon has a regeneration potential after
      harvesting for anterior cruciate ligament reconstruction.

PMID- 18818902
TI  - Tramadol-induced block of hyperpolarization-activated cation current in rat
      pituitary lactotrophs.
AB  - The hyperpolarization-activated cation current (I (h)) in rat pituitary
      lactotrophs (GH(3) cells) was characterized. Tramadol-induced block of this
      current was investigated. Effects of various related compounds on I (h) in GH(3)
      cells were also compared. Tramadol caused a time- and concentration-dependent
      reduction in the amplitude of I (h) with an IC(50) value of 13.6 microM. ZD7288
      (30 microM), CsCl (2 mM), and propofol (30 microM) were effective in suppressing
      the amplitude of I (h). 2',5'-dideoxyadenosine (100 microM) suppressed I (h),
      while sp-cAMPS (100 microM) had no effect on it. Tramadol (10 microM) shifted the
      activation curve of I (h) to a more negative potential by approximately -20 mV,
      although no change in the slope factor was observed. Under current-clamp
      configuration, tramadol (10 microM) could reduce the firing frequency of action
      potentials. Intracellular Ca(2+) measurements revealed its ability to reduce
      spontaneous Ca(2+) oscillations in GH(3) cells. The results suggests that during
      cell exposure to tramadol used at clinically relevant concentration, the tramadol
      mediated inhibition of I (h) could be direct and mediated via a non-opioid
      mechanism and would be one of the ionic mechanisms underlying reduced cell
      excitability.

PMID- 18818904
TI  - Brain activation by short-term nicotine exposure in anesthetized wild-type and
      beta2-nicotinic receptors knockout mice: a BOLD fMRI study.
AB  - RATIONALE: The behavioral effects of nicotine and the role of the beta2
      containing nicotinic receptors in these behaviors are well documented. However,
      the behaviors altered by nicotine rely on the functioning on multiple brain
      circuits where the high-affinity beta2-containing nicotinic receptors
      (beta2*nAChRs) are located. OBJECTIVES: We intend to see which brain circuits are
      activated when nicotine is given in animals naive for nicotine and whether the
      beta2*nAChRs are needed for its activation of the blood oxygen level dependent
      (BOLD) signal in all brain areas. MATERIALS AND METHODS: We used functional
      magnetic resonance imaging (fMRI) to measure the brain activation evoked by
      nicotine (1 mg/kg delivered at a slow rate for 45 min) in anesthetized C57BL/6J
      mice and beta2 knockout (KO) mice. RESULTS: Acute nicotine injection results in a
      significant increased activation in anterior frontal, motor, and somatosensory
      cortices and in the ventral tegmental area and the substantia nigra. Anesthetized
      mice receiving no nicotine injection exhibited a major decreased activation in
      all cortical and subcortical structures, likely due to prolonged anesthesia. At a
      global level, beta2 KO mice were not rescued from the globally declining BOLD
      signal. However, nicotine still activated regions of a meso-cortico-limbic
      circuit likely via alpha7 nicotinic receptors. CONCLUSIONS: Acute nicotine
      exposure compensates for the drop in brain activation due to anesthesia through
      the meso-cortico-limbic network via the action of nicotine on beta2*nAChRs. The
      developed fMRI method is suitable for comparing responses in wild-type and mutant
      mice.

PMID- 18818905
TI  - Methylphenidate improves response inhibition but not reflection-impulsivity in
      children with attention deficit hyperactivity disorder (ADHD).
AB  - RATIONALE: Impulsivity is a cardinal feature of attention deficit hyperactivity
      disorder (ADHD), which is thought to underlie many of the cognitive and
      behavioural symptoms associated with the disorder. Impairments on some measures
      of impulsivity have been shown to be responsive to pharmacotherapy. However,
      impulsivity is a multi-factorial construct and the degree to which different
      forms of impulsivity contribute to impairments in ADHD or respond to
      pharmacological treatments remains unclear. OBJECTIVES: The aims of the study
      were to assess the effects of methylphenidate (MPH) on the performance of
      children with ADHD on measures of reflection-impulsivity and response inhibition
      and to compare with the performance of healthy volunteers. METHODS: Twenty-one
      boys (aged 7-13 years) diagnosed with ADHD underwent a double-blind, placebo
      controlled trial of MPH (0.5 mg/kg) during which they performed the Information
      Sampling Task (IST) and the Stop Signal Task. A healthy age- and education
      matched control group was tested on the same measures without medication.
      RESULTS: Children with ADHD were impaired on measures of response inhibition, but
      did not demonstrate reflection-impulsivity on the IST. However, despite sampling
      a similar amount of information as their peers, the ADHD group made more poor
      decisions. MPH improved performance on measures of response inhibition and
      variability of response, but did not affect measures of reflection-impulsivity or
      quality of decision-making. CONCLUSIONS: MPH differentially affected two forms of
      impulsivity in children with ADHD and failed to ameliorate their poor decision
      making on the information sampling test.

PMID- 18818906
TI  - Fiber-packed needle-type sample preparation device designed for gas
      chromatographic analysis.
AB  - A miniaturized sample preparation technique that uses a fine-fiber-packed needle
      as the extraction medium is reviewed, especially in relation to its application
      to the analysis of volatile organic compounds by gas chromatography. When the
      needle was packed longitudinally with a bundle of fine filaments (12 microm o.d.)
      which were also surface-coated with polymeric materials, successful sample
      preconcentration was obtained. Improved sensitivity was also established by
      introducing simultaneous derivatization reactions into the extraction process in
      the fiber-packed needle. The storage performance of the needle clearly
      demonstrated the potential of the technique for typical on-site sampling during
      environmental analysis. In this short review, the fiber-packed extraction needle
      developed by the authors is summarized along with applications that use the fiber
      packed needle as a miniaturized extraction device.

PMID- 18818907
TI  - Positional and directional preponderances in vection.
AB  - We examined the biases in vection strength caused by motion direction
      (temporonasal vs. nasotemporal motion) and position of stimulus presentation
      (nasal and temporal semi-retinas) to investigate a subcortical contribution to
      vection. These biases have been identified for optokinetic nystagmus (OKN) and
      are acknowledged as evidence for a subcortical origin of OKN. In experiments,
      subjects monocularly observed hemi-field motion stimuli and made magnitude
      estimations. The results indicated significant directional and positional biases
      when luminance modulated gratings were used as stimuli. Vection was stronger with
      nasotemporal motions and nasal retina presentations, but there were no
      interactions between the two factors. However, these biases disappeared for
      second-order motion stimuli (contrast modulation), which are presumably processed
      by the cortex. In addition, when subjects were asked to make subjective ratings
      of motion impression, there was no significant difference in subjective strength
      between the stimuli that induced the strongest vection and weakest vection. These
      results, together, suggest the involvement of the subcortical pathway in vection
      induction.

PMID- 18818908
TI  - Decreasing task-related brain activity over repeated functional MRI scans and
      sessions with no change in performance: implications for serial investigations.
AB  - For prospective functional imaging studies of learning and for clinical studies
      of recovery or disease progression, it is important that the magnitude of brain
      activity does not exhibit a trend over repeated sessions in the absence of
      changes in task performance. This may confuse the interpretation of proposed
      mechanisms. The objective of this study was to use functional magnetic resonance
      imaging to determine if a linear trend in brain activity was present for simple
      and commonly used motor and cognitive tasks. Fourteen healthy individuals
      participated in three sessions on different days during which four scans each of
      a finger flexion task and a working memory task were performed in a block design.
      The general linear model was used to determine brain regions exhibiting activity
      differences between sessions conducted on different days, as well as between
      scans performed within the same session. Task-related brain activity decreased
      over sessions and scans in prefrontal and frontal cortices for both tasks. No
      increases, nor quadratic trends, were detected. Activity within premotor and
      ipsilateral primary somatosensory cortex decreased over scans for externally cued
      finger flexion and over sessions for self-paced finger flexion. Activity within
      parietal cortex and contralateral supplementary motor area decreased over
      sessions for all forms of finger flexion. These results suggest that motor
      planning and sensory regions, as well as frontal and parietal cortices, exhibit
      linear decreasing brain activity over repeated sessions in the absence of changes
      in task performance for even the simplest block design paradigms.

PMID- 18818909
TI  - Combined effects of preceding muscle vibration and contraction on the tonic
      vibration reflex.
AB  - As a result of intrafusal thixotropy, muscle contraction at a short length
      followed by passive lengthening enhances the subsequent tonic vibration reflex
      (TVR). We studied the effects of muscle vibration, contraction, and their
      combination on the subsequent TVR in the left biceps in 20 healthy men. The
      preceding vibration (20 or 80 Hz) conditioning at a short or long length was
      applied to the muscle belly with and without a contraction. After conditioning,
      distal tendon vibration (80 Hz) was used to elicit the TVR at the test length.
      The strength of the TVR was measured by surface electromyography. Conditioning
      with 80-Hz vibration at a short length followed by passive lengthening enhanced
      the subsequent TVR, which was greater in the presence than in the absence of a
      conditioning contraction. These results suggest that vibration and contraction
      work synergistically to develop intrafusal thixotropy.

PMID- 18818910
TI  - Adjuvant revascularization of intracranial artery occlusion with angioplasty
      and/or stenting.
AB  - INTRODUCTION: In conjunction with intravenous and/or intra-arterial thrombolysis,
      adjuvant revascularization of intracranial artery occlusion by angioplasty vs.
      stenting remains controversial. We evaluated outcome in patients with
      intracranial occlusion after angioplasty and/or stenting. MATERIALS AND METHODS:
      Thirty-three patients who underwent angioplasty or stenting (17 stenting and 16
      angioplasty) for intracranial arterial occlusion during the past 5 years were
      enrolled from prospective neurointerventional database. We compared
      recanalization rate [defined as thrombolysis in myocardial infarction (TIMI)
      grade II/III flow], adverse events, and clinical outcome [modified Rankin scale
      (mRS) at 1 and 6 months]. We also tried to determine independent variables
      associated with clinical outcome. RESULTS: Median initial National Institutes of
      Health Stroke Scale (NIHSS) was 13 and median time to treatment was 12 h from
      symptom onset. The successful recanalization rate was mean 79%. Symptomatic
      hemorrhage occurred in 15% (5/33). Events (27%, 9/33) at 1 month included four
      deaths, four major, and one minor stroke. Good outcome (mRS <or= 2) was achieved
      in 17 patients (52%) at 6 months and was significantly related to age, initial
      NIHSS, TIMI flow, and stenting on bivariate analysis. On multivariable analysis,
      stenting was the only variable significantly associated with a 6-month, good
      clinical outcome (OR, 14.48; 95% CI, 1.76 to 118.93; p = 0.013) CONCLUSION:
      Intracranial revascularization with angioplasty and/or stenting may improve the
      clinical outcome in selected patients with intracranial occlusion. Multiple
      factors are related to favorable clinical outcome.

PMID- 18818912
TI  - Acute rib fracture diagnosis in an infant by US: a matter of child protection.
AB  - Rib fractures in infants and children are highly specific for inflicted injury in
      the absence of a major accidental injury or underlying bone disorder. We present
      a 9-week-old infant diagnosed with an acute rib fracture by US at the site where
      physicians palpated chest wall crepitus when no rib fractures had been visualized
      on the skeletal survey, including oblique views of the ribs. Based on the US
      diagnosis of the acute rib fracture the infant was taken into protective custody.
      Follow-up skeletal survey 2 weeks later revealed healing fractures of the left
      6th and 7th posterolateral ribs and right 7th, 8th and 9th anterolateral ribs. We
      were unable to locate previous reports describing the diagnosis of rib fractures
      in infants by US.

PMID- 18818913
TI  - Ectopic drainage of the common bile duct into the lesser curvature of the gastric
      antrum in a newborn with pyloric atresia, annular pancreas and congenital short
      bowel syndrome.
AB  - We report a newborn with bilious vomiting and the rare combination of pyloric
      atresia, annular pancreas and ectopic drainage of the common bile duct into the
      lesser curvature of the gastric antrum. Radiologic, sonographic and percutaneous
      transhepatic transcholecystic cholangiographic (PTTC) findings, with surgical
      correlation, are presented.

PMID- 18818914
TI  - Model for fluorescence quenching in light harvesting complex II in different
      aggregation states.
AB  - Low-temperature (77 K) steady-state fluorescence emission spectroscopy and
      dynamic light scattering were applied to the main chlorophyll a/b protein light
      harvesting complex of photosystem II (LHC II) in different aggregation states to
      elucidate the mechanism of fluorescence quenching within LHC II oligomers.
      Evidences presented that LHC II oligomers are heterogeneous and consist of large
      and small particles with different fluorescence yield. At intermediate detergent
      concentrations the mean size of the small particles is similar to that of
      trimers, while the size of large particles is comparable to that of aggregated
      trimers without added detergent. It is suggested that in small particles and
      trimers the emitter is monomeric chlorophyll, whereas in large aggregates there
      is also another emitter, which is a poorly fluorescing chlorophyll associate. A
      model, describing populations of antenna chlorophyll molecules in small and large
      aggregates in their ground and first singlet excited states, is considered. The
      model enables us to obtain the ratio of the singlet excited-state lifetimes in
      small and large particles, the relative amount of chlorophyll molecules in large
      particles, and the amount of quenchers as a function of the degree of
      aggregation. These dependencies reveal that the quenching of the chl a
      fluorescence upon aggregation is due to the formation of large aggregates and the
      increasing of the amount of chlorophyll molecules forming these aggregates. As a
      consequence, the amount of quenchers, located in large aggregates, is increased,
      and their singlet excited-state lifetimes steeply decrease.

PMID- 18818915
TI  - Application of sandwich ELISA for detecting tag fusion proteins in high
      throughput.
AB  - Based on a series of mAbs against four frequently used tags--the human Ig Fc
      fragment, GST, maltose-binding protein, and thioredoxin--we developed
      corresponding sandwich enzyme-linked immunosorbent assay (ELISA) to detect these
      tag fusion proteins. As a supplement for Western blot, the successfully
      established ELISA was specific, sensitive, quantitative, easy to perform, time
      saving, and last but not least, suitable for high-throughput screening of tag
      fusion proteins. Determination of soluble tag fusion proteins expressed by
      various systems with the sandwich ELISA developed in the present study could be a
      valuable and promising tool for the wide application of tag-protein fusion
      systems in the rapidly growing field of proteomics research.

PMID- 18818916
TI  - Protocol for measuring myocardial blood flow by PET/CT in cats.
AB  - PURPOSE: The aim of this study was to establish a protocol for measuring
      myocardial blood flow (MBF) by PET/CT in healthy cats. The rationale was its
      future use in Maine Coon cats with hypertrophic cardiomyopathy (HCM) as a model
      for human HCM. METHODS: MBF was measured in nine anaesthetized healthy cats using
      a PET/CT scanner and (13)NH(3) at rest and during adenosine infusion. Each cat
      was randomly assigned to receive vasodilator stress with two or three adenosine
      infusions at the following rates (microg/kg per minute): 140 (Ado 1, standard
      rate for humans), 280 (Ado 2, twice the human standard rate), 560 (Ado 4), 840
      (Ado 6) and 1,120 (Ado 8). RESULTS: The median MBF at rest was 1.26 ml/min per g
      (n = 9; range 0.88-1.72 ml/min per g). There was no significant difference at Ado
      1 (n = 3; median 1.35, range 0.93-1.55 ml/min per g; ns) but MBF was
      significantly greater at Ado 2 (n = 6; 2.16, range 1.35-2.68 ml/min per g; p <
      0.05) and Ado 4 (n = 6; 2.11, 1.92-2.45 ml/min per g; p < 0.05). Large ranges of
      MBF values at Ado 6 (n = 4; 2.53, 2.32-5.63 ml/min per g; ns) and Ado 8 (n = 3;
      2.21, 1.92-5.70 ml/min per g; ns) were noted. Observed adverse effects, including
      hypotension, AV-block and ventricular premature contractions, were all mild, of
      short duration and immediately reversed after cessation of the adenosine
      infusion. CONCLUSION: MBF can be safely measured in cats using PET. An
      intravenous adenosine infusion at a rate of 280 microg/kg per minute seems most
      appropriate to induce maximal hyperaemic MBF response in healthy cats. Higher
      adenosine rates appear less suitable as they are associated with a large
      heterogeneity in flow increase and rate pressure product, most probably due to
      the large variability in haemodynamic and heart rate response.

PMID- 18818917
TI  - Metabolic-flow relationships in primary breast cancer: feasibility of combined
      PET/dynamic contrast-enhanced CT.
AB  - PURPOSE: To assess the feasibility and first experience of combined (18)F-FDG
      PET)/dynamic contrast-enhanced (DCE) CT in evaluating breast cancer. METHODS:
      Nine consecutive female patients (mean age 64.2 years, range 52-74 years) with
      primary breast carcinoma were prospectively recruited for combined (18)F-FDG
      PET/DCE-CT. Dynamic CT data were used to calculate a range of parameters of
      tumour vascularity, and tumour (18)F-FDG uptake (standardized uptake value,
      SUVmax) was used as a metabolic indicator. RESULTS: One tumour did not enhance
      and was excluded. The mean tumour SUVmax was 7.7 (range 2.4-26.1). The mean
      values for tumour perfusion, perfusion normalized to cardiac output, standard
      perfusion value (SPV) and permeability were 41 ml/min per 100 g (19-59 ml/min per
      100 g), 0.56%/100 g (0.33-1.09%/100 g), 3.6 (2.5-5.9) and 0.15/min (0.09
      0.30/min), respectively. Linear regression analysis showed a positive correlation
      between tumour SUV and tumour perfusion normalized to cardiac output (r=0.55,
      p=0.045) and a marginal correlation between tumour SUV and tumour SPV (r=0.19,
      p=0.065). There were no significant correlations between tumour SUV and tumour
      perfusion (r=0.29, p=0.401) or permeability (r=0.03, p=0.682). CONCLUSION: The
      first data from combined (18)F-FDG-PET/DCE-CT in breast cancer are reported. The
      technique was successful in eight of nine patients. Breast tumour metabolic and
      vascular parameters were consistent with previous data from (15)O-H(2)O-PET.

PMID- 18818918
TI  - Assessment of various strategies for 18F-FET PET-guided delineation of target
      volumes in high-grade glioma patients.
AB  - PURPOSE: The purpose of the study is to assess the contribution of (18)F-fluoro
      ethyl-tyrosine ((18)F-FET) positron emission tomography (PET) in the delineation
      of gross tumor volume (GTV) in patients with high-grade gliomas compared with
      magnetic resonance imaging (MRI) alone. MATERIALS AND METHODS: The study
      population consisted of 18 patients with high-grade gliomas. Seven image
      segmentation techniques were used to delineate (18)F-FET PET GTVs, and the
      results were compared to the manual MRI-derived GTV (GTV(MRI)). PET image
      segmentation techniques included manual delineation of contours (GTV(man)), a 2.5
      standardized uptake value (SUV) cutoff (GTV(2.5)), a fixed threshold of 40% and
      50% of the maximum signal intensity (GTV(40%) and GTV(50%)), signal-to-background
      ratio (SBR)-based adaptive thresholding (GTV(SBR)), gradient find (GTV(GF)), and
      region growing (GTV(RG)). Overlap analysis was also conducted to assess
      geographic mismatch between the GTVs delineated using the different techniques.
      RESULTS: Contours defined using GTV(2.5) failed to provide successful delineation
      technically in three patients (18% of cases) as SUV(max) < 2.5 and clinically in
      14 patients (78% of cases). Overall, the majority of GTVs defined on PET-based
      techniques were usually smaller than GTV(MRI) (67% of cases). Yet, PET detected
      frequently tumors that are not visible on MRI and added substantially tumor
      extension outside the GTV(MRI) in six patients (33% of cases). CONCLUSIONS: The
      selection of the most appropriate (18)F-FET PET-based segmentation algorithm is
      crucial, since it impacts both the volume and shape of the resulting GTV. The 2.5
      SUV isocontour and GF segmentation techniques performed poorly and should not be
      used for GTV delineation. With adequate setting, the SBR-based PET technique may
      add considerably to conventional MRI-guided GTV delineation.

PMID- 18818919
TI  - Enhancement of superantigen activity and antitumor response of staphylococcal
      enterotoxin C2 by site-directed mutagenesis.
AB  - Bacterial superantigen staphylococcal enterotoxins (SEs) tremendously stimulate
      polyclonal T cells bearing particular TCR Vbeta domains when binding to MHC II
      molecules, suggesting that they could be a candidate of new antitumor agent.
      SEC2, an important member of superantigen family, has been used in clinical trial
      as an immunotherapy agent for cancer treatment in China, and obtained some
      encouraging effects. However, the presence of immunosuppression and endotoxic
      activity limits the therapeutic dosage of SEC2, and influences its antitumor
      effect in clinic. Therefore, the enhancement of superantigen activity and
      antitumor effect of SEC2 could effectively make compensation for the
      disadvantages mentioned above. In this study, a superantigen SEC2(T20L/G22E)
      mutant was generated by site-directed mutagenesis, and efficiently expressed in
      E. coli BL21(DE3). The results showed that SEC2(T20L/G22E) mutant exhibited a
      significantly enhanced superantigen activity and antitumor response, compared
      with native SEC2 in vitro. Further toxicity assay in vivo indicated that
      SEC2(T20L/G22E) mutant had no significant increase in emetic and pyrogenic
      activity compared with SEC2, which suggested that the mutant SEC2(T20L/G22E)
      could be used as a potentially powerful candidate for cancer immunotherapy, and
      could make compensation for the deficiency of native SEC2 in clinic.

PMID- 18818920
TI  - Haemoglobinopathies with high oxygen affinity. Experience of Erythropathology
      Cooperative Spanish Group.
AB  - Haemoglobinopathies are the world's most frequently found monogenic disorders. In
      the cases with high oxygen affinity, the decrease in the liberation of the oxygen
      determines a secondary erythrocytosis. In this work, we present 17 unrelated
      families of Caucasian race and of Spanish origin, with ten variants of
      haemoglobin or haemoglobinopathies with high oxygen affinity which were diagnosed
      in our laboratory. Of the ten haemoglobinopathies, in four (the Hb San Diego, the
      Hb Johnstown, the Hb Malmo and the Hb Columbia-Missouri), the change of amino
      acid affects zones of the contact alpha(1)beta(2); in two variants (the Hb
      Strasbourg and the Hb Syracuse), it affects the unions with 2,3-DPG in the
      central cavity; in the other two (the Hb Badalona and the Hb La Coruna), the
      cavity of contact with the group haem is affected; in one (Hb Bethesda), it
      affects the zone of contact alpha(1)beta(1;) and in one (Hb Olympia), the
      position 20 of the chain in the helix B in the surface of the protein is
      affected. In all cases, the change of amino acid, though of different form,
      facilitates that the quaternary structure of the haemoglobin becomes stable in
      its relaxed configuration so the transfer of oxygen and the P(50) value are
      decreased. All cases were sent to our laboratory because of shown erythrocytosis.
      In the majority of them, the diagnosis was done during an analysis of routine or
      for being relatives of the first ones.

PMID- 18818921
TI  - Cisplatin and weekly docetaxel with concurrent thoracic radiotherapy for locally
      advanced stage III non-small-cell lung cancer.
AB  - PURPOSE: Our objective was to assess the efficacy and toxicity of concurrent
      chemoradiotherapy with cisplatin + weekly divided-dose docetaxel in patients with
      stage III non-small-cell lung cancer (NSCLC). METHODS: A total of 34 patients
      aged less than 75 years old with locally advanced stage III NSCLC were enrolled.
      The patients received intravenous infusions of cisplatin (80 mg/m(2); day 1) and
      docetaxel (20 mg/m(2); days 1, 8, 15), followed by a week's drug-free interval.
      Standard concurrent thoracic radiotherapy was given for 6 weeks (2 Gy per
      fraction; total dose, 60 Gy). RESULTS: Over Grade 3 neutropenia, esophagitis and
      pulmonary toxicities were observed in 23.5, 17.6 and 11.8% of the cases,
      respectively. One complete response and 20 partial responses were obtained, with
      an objective response rate of 61.8%. The median survival time was 26.4 months
      (95% CI 16.9--not reached) and the 1- and 3-year survival rates were 76.5 and
      41.2%, respectively. CONCLUSION: Cisplatin + weekly docetaxel with concurrent
      radiotherapy is a feasible and effective regimen for locally advanced NSCLC.

PMID- 18818922
TI  - Experiences and practical conclusions concerning temsirolimus use and adverse
      event management in advanced renal cell carcinoma within a compassionate use
      program in Germany.
AB  - PURPOSE: To detail tolerance of temsirolimus in a routine practice setting within
      a compassionate use program for patients with renal cell carcinoma. METHODS: We
      treated 32 patients with advanced renal cell carcinoma with temsirolimus within
      the German compassionate use program on an individual patient basis free of
      charge according to EU guidelines at our two institutions. Twenty-five milligrams
      of temsirolimus was applied weekly in an inpatient clinical setting. Adverse
      events were classified following National Cancer Institute Common Toxicity
      Criteria. RESULTS: No dose modification or therapy interruptions were necessary
      due to adverse events. Adverse events like asthenia/fatigue were observed in
      43.8%, increased creatinine in 40.6%, mucositis in 31.3%, secondary diabetes in
      28.1%, hypothyreosis in 12.5% and rash in 12.5%, hypercholesterolemia and
      hypertriglyceridemia in 9.3% of the patients. CONCLUSION: Therapy with
      temsirolimus in advanced renal cell carcinoma is well tolerated. In a routine
      practice setting it results in a predictable adverse event profile that can be
      managed medically.

PMID- 18818923
TI  - Behcet's disease: clinical value of the video capsule endoscopy for small
      intestine examination.
AB  - We described a pilot study using Video capsule endoscopy (VCE) aiming the
      assessment of small bowel in Behcet's disease (BD). Ten patients with BD and
      abdominal complaints underwent VCE with Given Pillcam SB (Given Imaging Ltd.,
      Yoqneam). VCE revealed small bowel lesions in all ten subjects. Five patients had
      active symptoms of BD while five others had clinically inactive disease. Jejune
      was the most frequently affected GI segment being involved in eight cases, four
      from each group. We suggest that small bowel involvement may be frequent in BD
      patients, even in the absence of oral ulcerations.

PMID- 18818924
TI  - Clinical observations programme in SpA: disease parameters, treatment options and
      practical management issues.
AB  - Spondyloarthritides (SpAs) are a cluster of chronic inflammatory rheumatic
      diseases that typically involve inflammation of axial and peripheral joint or
      tendon and ligament insertions, distinct radiographic changes and diverse extra
      articular features. Conventional treatments relieve the signs and symptoms but do
      not prevent disease progression. TNFalpha inhibitors provide clinicians with the
      potential to treat the underlying pathology and to alter disease progression. By
      targeting the underlying inflammatory mechanisms, TNFalpha blockade can treat any
      extra-articular manifestations of SpA.

PMID- 18818925
TI  - Is leptin a significant predictor of bone mineral density in postmenopausal
      Turkish women?
AB  - The objective of the present study was to investigate the relationship between
      leptin and bone mineral density in postmenopausal Turkish women. A total of 122
      healthy postmenopausal women were enrolled in this cross-sectional study. Blood
      samples were obtained for analysis of serum leptin. Bone mineral density (BMD)
      was measured by dual-energy X-ray absorptiometry at the lumbar spine, femoral
      neck and trochanter on the same day. Leptin levels was significantly correlated
      with BMD of L(1-4) (P = 0.04), but not of femoral neck (P = 0.13), and trochanter
      (P = 0.39). However, Z scores of L(1-4) (P = 0.009), femur neck (P = 0.009), and
      femur trochanter (P = 0.025) were positively correlated with leptin levels. In
      multiple linear regression analysis, leptin was not found to be a statistically
      significant independent predictor for BMD. Leptin was associated with BMD and Z
      scores at various body sites; however, it was not an independent predictor of
      BMD.

PMID- 18818926
TI  - Strontium ranelate decreases plasma homocysteine levels in postmenopausal
      osteoporotic women.
AB  - We analyzed the effect of strontium ranelate treatment on plasma homocysteine
      (Hcy) levels in postmenopausal osteoporotic women. Forty-nine postmenopausal
      women diagnosed with osteoporosis with a mean age of 54.07 +/- 7.5 years (range
      40-70) who visited our menopause clinic were participated in this prospective
      study. Patients with bone mineral density (BMD) at least 2.5 SD below the average
      value in young adults (T score < -2.5) were considered to have osteoporosis.
      Patients received strontium ranelate 2 g/day (Servier) orally with additional
      calcium supplements. Fasting plasma Hcy levels were assessed at baseline, 3, 6
      and 12 months of the therapy with strontium ranelate. The mean plasma Hcy level
      (10.45 micromol/l) after 3 months of therapy was significantly lower compared to
      the basal plasma Hcy level (12.61 micromol/l) (P = 0.002). The plasma
      homocysteine level (10.54 micromol/l) of the 43 patients that were present at the
      6 months of the therapy was also significantly lower compared to the basal plasma
      Hcy level (P = 0.005). At the end of the 12 months of the study, there were 42
      patients. The plasma homocysteine level (10.107 micromol/l) at 12 months of
      therapy was also significantly lower compared to the basal Hcy level (P < 0.001).
      Strontium ranelate 2 g/day treatment for 1 year significantly decreases plasma
      Hcy levels in postmenopausal women with osteoporosis. Since the increased Hcy
      levels could lead to an increase risk of osteoporosis and fracture risk, this
      effect of strontium ranelate on Hcy level may cause additional benefit in terms
      of reducing the risk of fracture.

PMID- 18818927
TI  - Molecular analyses of the rice tubby-like protein gene family and their response
      to bacterial infection.
AB  - Tubby-like protein family has been identified in various multicellular organisms,
      indicating its fundamental functions in the organisms. However, the roles of
      plant tubby-like proteins are unknown. In this study, we have defined the tubby
      like protein gene (OsTLP) family with 14 members in rice. Most of the OsTLPs
      harbor a tubby domain in their carboxyl terminus and an F-box domain in the amino
      terminus. The expression of all the OsTLPs was induced on infection of
      Xanthomonas oryzae pv. oryzae, which causes bacterial blight, one of the most
      devastating diseases of rice worldwide. The maximal expression levels were
      observed at 2-8 h after infection for all the genes. Eight of the 14 OsTLPs were
      also responsive to wounding. All the OsTLPs showed differential expression in
      different tissues at different developmental stages. However, four pairs of the
      14 OsTLPs, with each pair having high sequence similarity and distributing on the
      similar position of different chromosomes, showed similar expression pattern in
      different tissues, indicating their direct relationship in evolution. These
      results suggest that the OsTLP family is involved in host-pathogen interaction
      and it may be also associated with other physiological and developmental
      activities.

PMID- 18818928
TI  - Detection of a SERK-like gene in coconut and analysis of its expression during
      the formation of embryogenic callus and somatic embryos.
AB  - Somatic embryogenesis involves different molecular events including differential
      gene expression and various signal transduction pathways. One of the genes
      identified in early somatic embryogenesis is S OMATIC E MBRYOGENESIS R ECEPTOR
      like K INASE (SERK). Cocos nucifera (L.) is one of the most recalcitrant species
      for in vitro regeneration, achieved so far only through somatic embryogenesis,
      although just a few embryos could be obtained from a single explant. In order to
      increase efficiency of this process we need to understand it better. Therefore,
      the purpose of the present work was to determine if an ortholog of the SERK gene
      is present in the coconut genome, isolate it and analyze its expression during
      somatic embryogenesis. The results showed the occurrence of a SERK ortholog
      referred to as CnSERK. Predicted sequence analysis showed that CnSERK encodes a
      SERK protein with the domains reported in the SERK proteins in other species.
      These domains consist of a signal peptide, a leucine zipper domain, five LRR, the
      Serine-Proline-Proline domain, which is a distinctive domain of the SERK
      proteins, a single transmembrane domain, the kinase domain with 11 subdomains and
      the C terminal region. Analysis of its expression showed that it could be
      detected in embryogenic tissues before embryo development could be observed. In
      contrast it was not detected or at lower levels in non-embryogenic tissues, thus
      suggesting that CnSERK expression is associated with induction of somatic
      embryogenesis and that it could be a potential marker of cells competent to form
      somatic embryos in coconut tissues cultured in vitro.

PMID- 18818929
TI  - Enhanced heat and drought tolerance in transgenic rice seedlings overexpressing
      OsWRKY11 under the control of HSP101 promoter.
AB  - An OsWRKY11 gene, which encodes a transcription factor with the WRKY domain, was
      identified as one of the genes that was induced by both heat shock and drought
      stresses in seedlings of rice (Oryza sativa L.). To determine if overexpression
      of OsWRKY11 confers heat and drought tolerance, OsWRKY11 cDNA was fused to the
      promoter of HSP101 of rice and introduced into a rice cultivar Sasanishiki.
      Overexpression of OsWRKY11 was induced by heat treatment. After heat
      pretreatment, the transgenic lines showed significant heat and drought tolerance,
      as indicated by the slower leaf-wilting and less-impaired survival rate of green
      parts of plants. They also showed significant desiccation tolerance, as indicated
      by the slower water loss in detached leaves. Our results indicate that the
      OsWRKY11 gene plays a role in heat and drought stress response and tolerance, and
      might be useful for improvement of stress tolerance.

PMID- 18818930
TI  - ACCURATUM: improved calcium volume scoring using a mesh-based algorithm--a
      phantom study.
AB  - To overcome the limitations of the classical volume scoring method for
      quantifying coronary calcifications, including accuracy, variability between
      examinations, and dependency on plaque density and acquisition parameters, a mesh
      based volume measurement method has been developed. It was evaluated and compared
      with the classical volume scoring method for accuracy, i.e., the normalized
      volume (measured volume/ground-truthed volume), and for variability between
      examinations (standard deviation of accuracy). A cardiac computed-tomography (CT)
      phantom containing various cylindrical calcifications was scanned using different
      tube voltages and reconstruction kernels, at various positions and orientations
      on the CT table and using different slice thicknesses. Mean accuracy for all
      plaques was significantly higher (p < 0.0001) for the proposed method (1.220 +/-
      0.507) than for the classical volume score (1.896 +/- 1.095). In contrast to the
      classical volume score, plaque density (p = 0.84), reconstruction kernel (p =
      0.19), and tube voltage (p = 0.27) had no impact on the accuracy of the developed
      method. In conclusion, the method presented herein is more accurate than
      classical calcium scoring and is less dependent on tube voltage, reconstruction
      kernel, and plaque density.

PMID- 18818931
TI  - [Exposure to light during vitreoretinal surgery. II: Characteristics of
      endoilluminators].
AB  - PURPOSE: Light can cause phototoxic retinal damage. The aim of this study was to
      evaluate the risk of retinal hazard by endoilluminators during vitreoretinal
      surgery. METHODS: The spectra, radiance, and irradiance of six light sources with
      different associated fibre optics (20 G, 23 G, standard collimated, wide-angle
      diffuse) were measured and compared with thresholds published by international
      standardisation committees. RESULTS: The spectra of the endoilluminators differed
      significantly in the short wavelength band. The maximum radiance ranged from 15
      mW to 190 mW and the calculated irradiance from 36 mW/cm2 to 1,130 mW/cm2
      (distance 5 mm) and from 9 mW/cm2 to 376 mW/cm2 (distance 10 mm). Compared with
      published thresholds for surgery, time limits ranging from 0.7 min to 264 min
      (distance 5 mm) and 2.7 min to 1,052 min (distance 10 mm) seem to be safe.
      CONCLUSIONS: Light systems used for vitreoretinal surgery differ considerably in
      spectra, radiance, and irradiance; these differences have an impact on the
      maximum tolerable exposure times during surgery.

PMID- 18818932
TI  - A K(+)/H (+) P-ATPase transport in the accessory cell membrane of the blowfly
      taste chemosensilla sustains the transepithelial potential.
AB  - An electrogenic K(+) transport in the tormogen cell of insect chemosensilla is
      involved in the generation and maintenance of the transepithelial potential
      (TEP). To gain more information about the K(+) transport system underlying the
      TEP generation and the location of its components in the plasma membrane of the
      tormogen cell, we studied the effects of inhibitors of K(+)/H(+) P-ATPase
      (bafilomycin A1, omeprazole and Na-orthovanadate), of K(+)/Cl(-) co-transport
      (bumetanide), of Cl(-) channels (NPPB) and of a K(+) channel blocker (BaCl(2)).
      The relationship between TEP amplitude and spike firing activity was also
      studied. Experiments were performed on the labellar chemosensilla of the blowfly
      Protophormia terraenovae using a modified tip-recording technique. Results show
      that: (a) K(+)/H(+) P-ATPase inhibitors significantly decrease the TEP, when
      properly applied to the labellum for 20 min, so as to reach the basolateral side
      of the plasma membrane, while no effect was detected when applied to the apical
      side, (b) bumetanide, NPPB and BaCl(2) decrease the TEP value only when
      administered to the apical side, (c) spike activity is positively correlated with
      the TEP. A model is proposed of the active and passive K(+) transports sustaining
      the TEP associated with the blowfly chemosensilla.

PMID- 18818933
TI  - Identification of miRNAs associated with tumorigenesis of retinoblastoma by miRNA
      microarray analysis.
AB  - INTRODUCTION: MicroRNAs (miRNAs) are small (approximately 22 nucleotides)
      regulatory RNAs which play fundamental roles in many human diseases, including
      cancer. There is no report on the miRNA expression profile of retinoblastoma.
      METHODS: This work was undertaken to identify differentially expressed miRNAs in
      human retinoblastoma tissues by microRNA microarray technique, and some miRNAs
      were verified using northern blot analysis and the in situ hybridization method.
      RESULTS: A cluster of microRNAs was identified as highly expressed in
      retinoblastoma, including hsa-miR-494, hsa-let-7e, hsa-miR-513-1, hsa-miR-513-2,
      hsa-miR-518c*, hsa-miR-129-1, hsa-miR-129-2, hsa-miR-198, hsa-miR-492, hsa-miR
      498, hsa-miR-320, hsa-miR-503, and hsa-miR-373*. CONCLUSION: These miRNAs are the
      first to be reported for human retinoblastoma and may play significant roles in
      regulating tumor genesis.

PMID- 18818934
TI  - A modified arthroscopic anterior cruciate ligament double-bundle reconstruction
      technique with autogenous quadriceps tendon graft: remnant-preserving technique.
AB  - Several techniques of anterior cruciate ligament (ACL) double-bundle
      reconstruction have been introduced to improve the functional outcome and restore
      normal kinematics of the knee. Meanwhile, a remnant-preserving technique was
      developed to preserve the proprioception and to enhance the revascularization of
      the reconstructed ACL. We developed double-bundle ACL reconstruction technique
      using autogenous quadriceps tendon graft while preserving the remnant. With this
      technique, two femoral sockets and one tibial tunnel are made. To preserve the
      remnant of the ACL, the rotational direction of the reamer was set to
      counterclockwise just before perforation of the tibial tunnel. To pass the graft
      more easily without disturbance of the remnant, the graft passage was achieved
      through the tibial tunnel. We suggest that the remnant-preserving technique could
      be an effective alternative considering its mechanical stability as well as the
      proprioception and vascularization recovery in arthroscopic double-bundle ACL
      reconstruction.

PMID- 18818935
TI  - Cirsoid aneurysm of the synovium of knee: a very rare pathology.
AB  - A 10-year-old male presented with pain and restriction of movements of left knee
      for 6 months. A lesion with hyperintensity on T2 weighted images was demonstrated
      in the anterior aspect of the left knee. Patient was treated with arthroscopic
      removal of the lesion which later on proved to be cirsoid aneurysm of the
      synovium. We could not find any other report of a "cirsoid aneurysm" in the
      synovium of a joint in the English literature. This case is probably the first
      report of cirsoid aneurysm in the synovium of a joint.

PMID- 18818936
TI  - Fifth metatarsal avulsion fracture: a rational basis for postoperative treatment.
AB  - BACKGROUND: Lacking rational basis for the postoperative treatment of fifth
      metatarsal avulsion fractures. METHODS: Biomechanical test of stability of
      tension banding and screw fixation of fifth metatarsal avulsion fractures in
      cadaver specimen, sonographic measuring of the maximum cross-section of the
      peroneus brevis muscle, electromyographic examinations of the activity of the
      peroneus brevis muscle at different loads and means of immobilization. RESULTS:
      The forces acting on the base of the fifth metatarsal bone during voluntary
      activation of the peroneus brevis muscle or activation in the gait cycle are of
      the same magnitude as the failure forces of internal fixation. Immobilization of
      the talocrural joint achieves no reduction in muscle activation. Partial weight
      bearing reduces muscle activation. CONCLUSIONS: The postoperative treatment after
      osteosynthesis of fifth metatarsal avulsion fractures should be partial weight
      bearing. For safety reasons we add an elastic ankle orthesis to prevent
      supination. A below-knee cast is not necessary.

PMID- 18818937
TI  - Celiac disease during pregnancy: to screen or not to screen?
AB  - Permanent intolerance to gluten, known as celiac disease, affects both fertility
      and pregnancy outcomes when left untreated. Recent research on celiac disease and
      reproduction urge increased screening for celiac disease. While this may be
      beneficial for couples facing idiopathic infertility or those from particular
      risk groups, screening involves its own risks and expenses, and has not been
      consistently proven effective for the general population while pregnant. The
      present editorial discusses the potential advantages and disadvantages of
      screening during pregnancy and examines when screening may be helpful.

PMID- 18818938
TI  - Pregnancy in chronic renal insufficiency: single centre experience from North
      India.
AB  - BACKGROUND: Renal disease during pregnancy is relatively uncommon. The diagnosis
      of renal disease before or during pregnancy was only 0.03% in a population-based
      study of pregnant women with kidney disease. However, there is a paucity of
      scientific data regarding the general topic of renal disease in pregnancy on
      which to base clinical management and counselling recommendations. MATERIALS AND
      METHODS: A retrospective analysis of 14 year period was carried out in a referral
      hospital in northern India. Pregnant women were analyzed with respect to degree
      of renal impairment for the effect of renal disease on course of pregnancy,
      complications during pregnancy and perinatal outcome. RESULTS: Outcome of 30
      pregnancies (29 women) was available during the study period of 14 years.
      Pregnancy outcome was comparable in all types of glomerulonephritis. Progression
      of the disease during pregnancy was observed in total six patients. Proteinuria
      was in the range of 800 mg/day to 6.2 g/day (2.802 +/- 1.519 g/day). Anemia was
      identified in 12(46.1%) and 3(7.7%) required multiple blood transfusions. Twenty
      four (90%) women developed hypertension during pregnancy. Mild hypertension was
      seen in 40% patients and, 43.3% had severe hypertension requiring drug therapy.
      Obstetrical complications included a high frequency of preterm delivery (85%) and
      caesarean section (30%). Overall fetal survival rate was 77%. CONCLUSIONS: Most
      women with chronic renal disease will have a successful outcome if they receive
      proper prenatal care. Pregnant women with moderate or severe renal insufficiency
      have increased rates of complications due to worsening renal function,
      hypertension, and other obstetrical complications, but fetal survival is high.

PMID- 18818939
TI  - Collision tumor: serous cystadenocarcinoma and dermoid cyst in the same ovary.
AB  - INTRODUCTION: Collision tumor means the coexistence of two adjacent, but
      histologically distinct tumors without histologic admixture in the same tissue or
      organ. Collision tumors involving ovaries are extremely rare. CASE: We present a
      case of 45-year-old parous woman with a left dermoid cyst, with unusual imaging
      findings, massive ascites and peritoneal carcinomatosis. The patient underwent
      cytoreductive surgery. The histopathology revealed a collision tumor consisting
      of an invasive serous cystadenocarcinoma and a dermoid cyst.

PMID- 18818940
TI  - Obstructive nephropathy and chronic kidney disease secondary to uterine
      leiomyomas.
AB  - We present three cases of chronic kidney disease secondary to large fibroid
      uterus. The difficulties experienced in their clinical management and a review of
      literature is outlined.

PMID- 18818941
TI  - Reliability of the nociceptive flexor reflex (RIII) threshold and association
      with Pain threshold.
AB  - The purpose of this study was to assess the reliability of the RIII reflex
      threshold and Pain threshold in three repeated trials using electrocutaneous
      stimuli. Each trial was separated by a mean of 4.3 +/- 2.9 days (between-trials)
      and included two repeated measurements (within-trial) of the RIII reflex
      threshold (RIII-T) and the Pain threshold (PT) separated by 20 min. The
      participants were 14 healthy males (mean age +/- SD, 23.5 +/- 5.3 years). There
      was a significant difference between the RIII-T and PT. The reliability of the
      RIII-T and PT shows a between-trials coefficient of variance (CV(SEM)) of 16.1
      and 16.9%, respectively. The within-trial CV(SEM) for RIII-T and PT was 5.4 and
      4.3%, respectively. There was a significant correlation between the RIII-T
      threshold and PT. The parallel association and correlation of the RIII-T with the
      PT suggests that the RIII-T is valid in experimental pain studies under
      standardised resting conditions.

PMID- 18818942
TI  - Primary splenic diffuse large B-cell lymphoma manifesting in red pulp.
AB  - We evaluated six cases of diffuse large B-cell lymphoma (DLBCL) involving the red
      pulp of the spleen. All had B symptoms and an aggressive clinical course. The
      lymphoma cells proliferated diffusely and non-cohesively in the cords of the red
      pulp. The lymphoma involved the bone marrow in four of the five patients and the
      liver in all four of the patients examined. However, lymph node (LN) involvement
      was rare at presentation, and systemic LN involvement was not observed even in
      the terminal phase. The lymphoma cells infiltrated the
      intrasinusoidal/intravascular and interstitial spaces of the involved tissues and
      were detected in the peripheral blood in two of the six patients. CD5-expressing
      lymphoma cells were detected in four of the five patients examined. Because these
      cases had some unique clinical features and occurred in distinct splenic sites,
      we proposed that primary splenic DLBCL manifesting in red pulp is a distinct
      clinicopathological entity.

PMID- 18818943
TI  - Could the truncated variant of ERBB2 be present in the squamous carcinomas of the
      cervix?
AB  - ERBB2, a ligand-less membrane receptor, is frequently overexpressed in a number
      of human tumors, contributing to uncontrolled cell proliferation. In some cases,
      gene amplification correlates with protein overexpression and predicts response
      to trastuzumab. We analyzed the expression of ERBB2 in a group of 40 patients
      diagnosed with infiltrating squamous cervical carcinomas (ISCC) using a
      microarray. Immunochemistry was performed using two different antibodies, one
      against the extramembrane domain and the other one for the intramembrane domain.
      Ten of the 40 cases included in the study could not be evaluated. Of the 30
      remaining biopsies, 13 (42%) showed immunoreactivity only with the antibody
      against the intramembrane domain. In 5 (16.12%), both intramembrane and
      extramembrane immunoreactivity was observed, and 12 (40%) were negative for both
      antibodies. Looking at our results, we propose that, in some ISCC, there is a
      rupture of the ERBB2 receptor, and this event, with slight genetic amplification,
      could explain the unfavorable response to trastuzumab observed in some ISCC
      descript for some authors.

PMID- 18818944
TI  - Prevention of hypernatraemic dehydration in breastfed newborn infants by daily
      weighing.
AB  - Hypernatraemic dehydration, which predominantly appears in breastfed neonates,
      can cause serious complications, such as convulsions, permanent brain damage and
      death, if recognised late. Weight loss > or = 10% of birth weight could be an
      early indicator for this condition. In this prospective cohort study from October
      2003 to June 2005 in the postnatal ward of the University Hospital Zurich,
      Switzerland, all term newborns with birth weight > or = 2,500 g were weighed
      daily until discharge. When the weight loss was > or = 10% of birth weight, serum
      sodium was measured from a heel prick. Infants with moderate hypernatraemia
      (serum sodium = 146-149 mmol/l) were fed supplementary formula milk or
      maltodextrose 10%. Infants with severe hypernatraemia (serum sodium > or = 150
      mmol/l) were admitted to the neonatal unit and treated in the same way, with or
      without intravenous fluids, depending on the severity of the clinical signs of
      dehydration. A total of 2,788 breastfed healthy term newborns were enrolled.
      Sixty-seven (2.4%) newborns had a weight loss > or = 10% of birth weight; 24
      (36%) of these had moderate and 18 (27%) severe hypernatraemia. Infants born by
      caesarean section had a 3.4 times higher risk for hypernatraemia than those born
      vaginally. All newborns regained weight 24 h after additional fluids. CONCLUSION:
      In our study, one out of 66 healthy exclusively breastfed term neonates developed
      hypernatraemic dehydration. Daily weight monitoring and supplemental fluids in
      the presence of weight loss > or = 10% of birth weight allows early detection and
      intervention, thereby preventing the severe sequellae of hypernatraemic
      dehydration.

PMID- 18818945
TI  - Bedside detection of low systemic flow in the very low birth weight infant on day
      1 of life.
AB  - We aimed to assess the relationship between the clinical and biochemical
      parameters of perfusion and superior vena cava (SVC) flow in a prospective
      observational cohort study of very low birth weight (VLBW) infants. Newborns with
      congenital heart disease were excluded. Echocardiographic evaluation of SVC flow
      was performed in the first 24 h of life. Capillary refill time (forehead, sternum
      and toe), mean blood pressure, urine output and serum lactate concentration were
      also measured simultaneously. Thirty-eight VLBW infants were examined. Eight
      patients (21%) had SVC flow less than 40 ml/kg/min. There was a poor correlation
      between the capillary refill time (in all sites), mean blood pressure, urine
      output and SVC flow. The correlation coefficient for the serum lactate
      concentration was r = -0.28, p = 0.15. The median serum lactate concentration was
      3.5 (range 2.8-8.5) vs. 2.7 (range 1.2-6.9) mmol/l (p = 0.01) in low flow versus
      normal flow states. A serum lactate concentration of >2.8 was 100% sensitive and
      60% specific for detecting a low flow state. Combining a capillary refill time of
      >4 s with a serum lactate concentration of >4 mmol/l had a specificity of 97% for
      detecting a low SVC flow state. Serum lactate concentrations are higher in low
      SVC flow states. A capillary refill time of >4 s combined with serum lactate
      concentrations >4 mmol/l increased the specificity and positive and negative
      predictive values of detecting a low SVC flow state.

PMID- 18818946
TI  - A novel non-sense mutation in the SLC2A10 gene of an arterial tortuosity syndrome
      patient of Kurdish origin.
AB  - Arterial tortuosity syndrome (ATS) is a rare autosomal recessive disorder in
      which patients display tortuosity of arteries in addition to hyperextensible
      skin, joint laxity, and other connective tissue features. This syndrome is caused
      by mutations in the SLC2A10 gene. In this article we describe an ATS girl of
      Kurdish origin who, in addition to arterial tortuosity and connective tissue
      features, displays stomach displacement within the thorax and bilateral hip
      dislocation. Clinical details of this patient have been reported previously.
      Sequencing of the SLC2A10 gene identified a novel homozygous non-sense c.756C>A
      mutation in this patient's DNA. This mutation in the SLC2A10 gene replaces a
      cysteine encoding codon with a stop signal. This is believed to cause a premature
      truncation of GLUT10 protein in this patient. We conclude that patients of
      Kurdish origin who display arterial tortuosity associated with skin
      hyperextensibility, joint hypermobility, and characteristic facial features may
      carry mutations in the SLC2A10 gene.

PMID- 18818947
TI  - Hypophosphatasia may lead to bone fragility: don't miss it.
AB  - Hypophosphatasia is an inheritable disorder characterised by defective bone
      mineralisation due to the impaired activity of tissue-non-specific alkaline
      phosphatase (AP). Clinical presentation ranges from stillbirth without
      mineralised bone to pathological fractures in late adulthood. During childhood,
      the main manifestations include rickets, growth delay and dental problems.
      Fractures and bone pain usually characterise the adult form. A 9-year-old girl
      was referred for repetitive fractures after minimal trauma. She had normal
      growth, normal sclerae, no rickets and minimal dental abnormalities. Her sister
      had also presented fractures. The proband, her sister and mother had low total
      and bone-specific AP levels and E435K mutation in exon 12 of the
      liver/bone/kidney AP gene. Low AP levels must lead to genetic analysis. Bone
      fragility and repetitive fractures may be symptoms of hypophosphatasia in
      childhood, which must not be neglected. Associated factors such as vitamin D or
      calcium deficiency must be prevented. In conclusion, hypophosphatasia must not be
      forgotten as an aetiological factor of repetitive fractures or bone pain in
      children and AP activity should be checked accurately.

PMID- 18818948
TI  - The prevalence of microsatellite instability in head and neck squamous cell
      carcinoma.
AB  - PURPOSE: The present study aimed to use the most definitive available techniques
      to resolve controversy in the literature as to the prevalence of microsatellite
      instability (MSI) in head and neck squamous cell carcinoma (HNSCC). METHODS:
      Eighty patients with advanced HNSCC were enrolled in the study that examined 20
      microsatellite markers with automatic fragment analysis. These markers included
      ones derived from the NCI reference panel and ones previously reported to detect
      MSI in HNSCC (HNSCC panel). RESULTS: Only one of 80 tumors could be considered
      positive for MSI. For this case, both panels showed MSI-High (8/10 positive
      markers for the NCI reference panel and 6/10 positive markers for the HNSCC
      panel). Qualitatively, the observed MSI could be classified as Type B MSI.
      CONCLUSIONS: The present results indicate that MSI has a low prevalence in HNSCC.

PMID- 18818949
TI  - PCR-based detection and genotyping of haematozoa (Protozoa) parasitizing eagle
      owls, Bubo bubo.
AB  - We genetically analysed haematozoa parasites (Protozoa) isolated from nestling
      eagle owls (Bubo bubo) in Toledo province, Central Spain. A total of 206
      nestlings from 74 nests were screened for parasites of the genera Leucocytozoon,
      Plasmodium, and Haemoproteus using a very efficient polymerase chain reaction
      (PCR) approach that amplifies a partial segment of the mitochondrial cytochrome b
      gene of these parasites. PCR-based detection and sequence analyses revealed a
      unique lineage of Leucocytozoon (EO1) parasitizing nestling eagle owls. Ocular
      examination of blood smears identified these parasites as Leucocytozoon ziemanni,
      the only species deemed valid in owls based on morphology. Preliminary
      phylogenetic analyses using homologous published sequences isolated from other
      owl species suggest that L. ziemanni constitutes a monophyletic clade that may be
      composed by a complex of genetically differentiated cryptic species.

PMID- 18818950
TI  - Larvicidal and oviposition activity of Cassia obtusifolia Linn (Family:
      Leguminosae) leaf extract against malarial vector, Anopheles stephensi Liston
      (Diptera: Culicidae).
AB  - The ethanolic leaf extract of Cassia obtusifolia was investigated for their
      larvicidal and oviposition deterrence effects against Anopheles stephensi.
      Concentrations ranging from 25 to 125 mg/l were assessed at 24 h post-treatment
      against late third instar larvae. The leaf extract had significant larvicidal
      effect with LC(50) and LC(90) values were 52.2 and 108.7 mg/l, respectively. In
      oviposition behaviour study, four different concentrations ranging from 100 to
      400 mg/l were studied against gravid female mosquitoes. The results of
      oviposition study indicated that the leaf extract showed concentration dependent
      oviposition deterrent activity. At higher concentration (400 mg/l) showed 92.5%
      effective repellency against oviposition, followed by 300, 200 and 100 mg/l
      showed 87.2%, 83.0% and 75.5%, respectively. The larvicidal and oviposition
      deterrent effect of C. obtusifolia against A. stephensi make this plant product
      promising as an alternative to synthetic insecticide in mosquito control
      programs.

PMID- 18818951
TI  - mRNA processing in Antonospora locustae spores.
AB  - Microsporidia are a group of intracellular parasites characterized by highly
      reduced and compact genomes. The presence of a high gene density had several
      consequences for microsporidian genomes, including a high frequency of overlap
      between transcripts of adjacent genes. This phenomenon is apparently widespread
      in microsporidia, and strongly correlated with gene density. However, all
      analyses to date have focused on one or a few transcripts from many loci, so it
      is unclear how diverse the pool of transcripts at a given locus may be. To
      address this question, we characterized initiation and termination points from 62
      transcripts in gene-dense regions in Antonospora locustae spores using both
      conventional and fluorescence-based RACE-PCR procedures. In parallel, we
      investigated the abundance and nature of transcripts along a 6 kb region
      surrounding the actin locus of A. locustae using northern blotting, RACE-PCR and
      previously characterised EST sequences. Overall, we confirmed previous
      suggestions that most transcripts in A. locustae spores overlap with the
      downstream gene, but that at the 5' end untranslated regions are very short and
      overlap is rare. From fluorescence-based RACE-PCR we show that transcription of
      most genes (31 out of 34) initiates at a single position, whereas 35% of loci
      analyzed with 3' RACE polyadenylate mRNA at several sites. Finally, we identified
      the presence of previously unsuspected and very large transcripts in A. locustae
      spores. Those transcripts were found to overlap up to four open reading frames in
      different strands, adding a novel layer of complexity in the mRNA transcription
      of this microsporidian species.

PMID- 18818952
TI  - Molecular and genetic characterization of the S locus in Hordeum bulbosum L., a
      wild self-incompatible species related to cultivated barley.
AB  - Gametophytic self-incompatibility (GSI) in the grasses is controlled by a
      distinct two-locus genetic system governed by the multiallelic loci S and Z. We
      have employed diploid Hordeum bulbosum as a model species for identifying the
      self-incompatibility (SI) genes and for elucidating the molecular mechanisms of
      the two-locus SI system in the grasses. In this study, we attempted to identify S
      haplotype-specific cDNAs expressed in pistils and anthers at the flowering stage
      in H. bulbosum, using the AFLP-based mRNA fingerprinting (AMF, also called cDNA
      AFLP) technique. We used the AMF-derived DNA clones as markers for fine mapping
      of the S locus, and found that the locus resided in a chromosomal region
      displaying remarkable suppression of recombination, encompassing a large physical
      region. Furthermore, we identified three AMF-derived markers displaying complete
      linkage to the S locus, although they showed no significant homology with genes
      of known functions. Two of these markers showed expression patterns that were
      specific to the reproductive organs (pistil or anther), suggesting that they
      could be potential candidates for the S gene.

PMID- 18818953
TI  - Small-scale spatial structure within patterns of seed dispersal.
AB  - A large proportion of dispersing propagules land near their maternal plant, even
      in species that have evolved structures which enhance dispersal. For these
      propagules, their post-dispersal spatial pattern is likely to reflect the overall
      shape and scale of the parental plant canopy and, especially in poorly dispersing
      species, aggregation of propagules on the plant prior to dispersal. Localised
      patterns within seed shadows are also likely to be affected by secondary movement
      after dispersal, leading to either more or less small-scale aggregation,
      depending on the mechanism. Our general aim was to study the small-scale spatial
      structure within patterns of seed dispersal of Raphanus raphanistrum L. to
      generate hypotheses about the sequence of processes and events leading to the
      spatial pattern of dispersal in this species. More specifically, we determined
      the sizes of small-scale structures within the seed shadows on the ground after
      dispersal and the extent to which these match the sizes of pre-dispersal
      aggregations within the parental canopy. Variation in plant size and shape was
      provided by four levels of inter-specific competition resulting from differing
      wheat crop densities. Positions of propagules were determined using a three
      dimensional digitizer, and the data for each plant were analysed using point
      pattern analysis. Not surprisingly, larger plants, growing at lower plant
      density, had larger seed shadows, showing an overall influence of maternal plant
      size. The pattern of propagules exhibited significant small-scale aggregates,
      with similar sizes on the plant and on the ground. There was no evidence that
      aggregation size was greater on the ground or increased with time, but the
      strength of the aggregation increased with length of time on the ground.

PMID- 18818954
TI  - Ceftibuten versus trimethoprim-sulfamethoxazole for oral treatment of febrile
      urinary tract infection in children.
AB  - A randomized, open, coordinated multi-center trial compared the bacteriological
      and clinical efficacy and safety of orally administered ceftibuten and
      trimethoprim-sulfamethoxazole (TMP-SMX) in children with febrile urinary tract
      infection (UTI). Children aged 1 month to 12 years presenting with presumptive
      first-time febrile UTI were eligible for enrollment. A 2:1 assignment to
      treatment with ceftibuten 9 mg/kg once daily (n = 368) or TMP-SMX (3 mg + 15
      mg)/kg twice daily (n = 179) for 10 days was performed. Escherichia coli was
      recovered in 96% of the cases. Among the E. coli isolates, 14% were resistant to
      TMP-SMX but none to ceftibuten. In the modified intention-to-treat population,
      the bacteriological elimination rates at follow-up did not differ significantly
      between patients treated with ceftibuten and those treated with TMP-SMX [91 vs.
      95%, with a 95% confidence interval (CI) for difference of -9.7 to 1.0]. However,
      the clinical cure rate was significantly higher among those treated with
      ceftibuten (93 vs. 83%, with a 95% CI for difference of 2.4 to 17.0). Adverse
      events were similar for both regimens and consisted mainly of gastrointestinal
      disturbances. In conclusion, ceftibuten is a safe and effective drug for the
      empirical treatment of febrile UTI in young children.

PMID- 18818955
TI  - Inherited forms of renal hypomagnesemia: an update.
AB  - The kidney plays an important role in ion homeostasis in the human body. Several
      hereditary disorders characterized by perturbations in renal magnesium
      reabsorption leading to hypomagnesemia have been described over the past 50
      years, with the most important of these being Gitelman syndrome, familial
      hypomagnesemia with hypercalciuria and nephrocalcinosis, familial hypomagnesemia
      with secondary hypocalcemia, autosomal dominant hypomagnesemia with
      hypocalciuria, and autosomal recessive hypomagnesemia. Only recently, following
      positional cloning strategies in affected families, have mutations in renal ion
      channels and transporters been identified in these diseases. In this short
      review, I give an update on these hypomagnesemic disorders. Elucidation of the
      genetic etiology and, for most of these disorders, also the underlying
      pathophysiology of the disease, has greatly increased our understanding of the
      normal physiology of renal magnesium handling. This is yet another example of the
      importance of studying rare disorders in order to unravel physiological and
      pathophysiological processes in the human body.

PMID- 18818956
TI  - High compatibility between arbuscular mycorrhizal fungal communities and
      seedlings of different land use types in a tropical dry ecosystem.
AB  - We conducted this study to explore limitations for the establishment of
      mycorrhizal associations in disturbed areas of the tropical dry ecosystem in the
      Chamela region of Jalisco, Mexico. Specifically, we: (1) assessed the diversity
      and composition of arbuscular mycorrhizal fungal (AMF) communities through spore
      morphospecies identification in three common land uses (primary forest, secondary
      forest, and pasture), (2) tested the inoculum potential of the AMF communities
      and the effect of water stress on the establishment of mycorrhizal associations
      in seedlings of various plant species, and (3) explored the importance of AMF
      community composition on early seedling development. Soil and root samples were
      taken from 15 random points in each of three plots established in two primary
      forests, two 26-year-old secondary forests, and two 26-year-old pastures. We
      expected that because of soil degradation and management, pastures would have the
      lowest and primary forests the highest AMF species richness. We found evidence
      for changes in AMF species composition due to land use and for higher
      morphospecies richness in primary forests than in secondary forests and pastures.
      We expected also that water stress limited plant and mycorrhizal development and
      that plants and AMF communities from secondary forests and pastures would be less
      affected by (better adapted to) water stress than those from the primary forest.
      We found that although all plant species showed biomass reductions under water
      stress, only some of the plant species had lower mycorrhizal development under
      water stress, and this was regardless of the AMF community inoculated. The third
      hypothesis was that plant species common to all land use types would respond
      similarly to all AMF communities, whereas plant species found mainly in one land
      use type would grow better when inoculated with the AMF community of that
      specific land use type. All plant species were however equally responsive to the
      three AMF communities inoculated, indicating that all plants established
      functionally compatible AMF in each community, with no preferences. The results
      suggest that early seedling growth and mycorrhizal development in secondary
      forests and pastures is not likely limited by diversity, quantity, or quality of
      mycorrhizal propagules but by the high temperature and water stress conditions
      prevailing at those sites.

PMID- 18818957
TI  - Reviewer's comment concerning "Predictive value of seven preoperative prognostic
      scoring systems for spinal metastases" (ESJO-D-08-00148R1/A. Leithner et al.).

PMID- 18818958
TI  - The in vitro susceptibility of Campylobacter spp. to the antibacterial effect of
      manuka honey.
AB  - We report the antimicrobial effect of manuka honey against Campylobacter spp.
      isolated by a diagnostic laboratory from specimens from a community in New
      Zealand. The isolates were differentiated according to species level using
      multiplex PCR. C. jejuni (20 strains) and C. coli (7 strains) were identified.
      The clinical isolates identified and type culture collection strains of these
      species were subjected to testing to determine the minimum inhibitory
      concentration (MIC) of manuka honey using a microdilution technique. The MIC of
      the manuka honey against all of the Campylobacter tested was found to be around
      1% (v/v) honey. The low MIC values suggest that honey might still inhibit the
      growth of campylobacteria after dilution by fluid in the gut, but the actual
      concentration of honey that can be achieved in the intestine is unknown.
      Therefore, clinical investigation is required to establish the efficacy of honey
      against Campylobacter spp. in the gut environment.

PMID- 18818959
TI  - Adverse effects of parenteral antimicrobial therapy for chronic bone infections.
AB  - Responsible pathogens of chronic bone infections (CBI) are frequently resistant,
      requiring parenteral antimicrobial therapy. Therefore, adverse effects may be
      observed. We have determined the rate of adverse effects of antimicrobial therapy
      for CBI in a retrospective study of all patients receiving parenteral drugs via
      an implantable port. Patients from one medical ward (n = 89) and from one
      surgical ward (n = 40) between January 1995 and December 2005 were included in
      this study. The CBI included were 85 osteomyelitis (66%) and 44 prosthetic joint
      infections (34%). The main group of pathogens was gram positive cocci (n = 144;
      65%). The total duration of antibiotic treatment was 205 +/- 200 days, including
      133 +/- 100 days for parenteral therapy. Thirty-three catheter-related
      complications were observed in 27 patients (21%). All complications led to
      hospitalization but none led to death. Twenty-one antibiotic-related
      complications occurred in 18 patients (16%), and one allergic reaction led to
      death. The mean duration of follow-up was 290 days. Remission was observed in 84
      patients (65%). In multivariate analysis, adverse effects were mostly observed in
      the medical department. Adverse effects affect at least one third of the patients
      treated for CBI with parenteral antimicrobial therapy and are related to both the
      implantable port and the antibiotic compounds.

PMID- 18818960
TI  - Current strategies for the treatment of intracranial atherosclerotic internal
      carotid artery stenosis.
AB  - We evaluate the current literature regarding treatment of intracranial
      atherosclerotic disease, with particular emphasis on emerging medical, surgical,
      and endovascular trials. A MEDLINE and PubMed search of the literature related to
      intracranial atherosclerotic disease was performed. Articles which discussed
      medical, surgical, and endovascular therapies were reviewed. Currently, best
      medical management of intracranial atherosclerotic stenosis consists of aspirin
      therapy. Despite this, a significant percentage of patients with high-grade
      stenoses experience recurrent stroke soon after their initial event. Although
      previous randomized trials demonstrated no benefit to performing intracranial
      extracranial bypass surgery in patients with intracranial atherosclerotic
      stenosis, current studies seem to suggest a benefit in a particular subset of
      these patients, specifically those with hemodynamic compromise. Endovascular
      therapy for intracranial atherosclerotic stenosis is in its infancy but is
      beginning to show technical promise. Nonetheless, real concerns exist regarding
      rates of in-stent restenosis, and large-scale follow-up studies must be completed
      before the true efficacy of endovascular therapies can be evaluated. Symptomatic
      intracranial atherosclerotic stenosis is associated with considerable morbidity
      and mortality. However, in a subgroup of patients, specifically those with high
      grade stenoses and hemodynamic compromise, the risk of morbidity and mortality is
      significantly higher. It is this group of patients that would most benefit from
      more aggressive interventions, as best medical therapy still results in a
      significant rate of recurrent strokes. The emergence of improved surgical and
      endovascular techniques will be of particular importance in treating these high
      risk patients.

PMID- 18818961
TI  - Surgical treatment of skull base chondrosarcomas.
AB  - Skull base chondrosarcomas are rare tumors and individual experience with their
      management is limited. We present a series of such tumors treated at our
      institution. Particular attention was paid to their extension pattern, choice of
      surgical approach, and outcome. Twenty-five patients were operated consecutively
      over a period of 19 years. Their clinical presentation, radiological features,
      surgical treatment, early and late treatment outcome, as well as survival rate
      were analyzed. The most frequent initial symptom was abducent palsy. The typical
      bone destruction of the petrous apex was found in 83%. Chondrosarcomas extended
      in 92% to the posterior cranial fossa. Total number of surgeries was 39. The
      operative approach was tailored to each case. The retrosigmoid approach was used
      in 30.8%, the pterional in 23%, and the transethmoid in 15.4%. Total tumor
      removal was achieved in 19 of the surgeries. New neurological deficits
      immediately after surgery appeared in 33.3%. The perioperative mortality was 0%.
      The average Karnofsky performance score at last follow-up was 91%, and 5- and 10
      year survival rates were 95%. Individually tailored approach in skull base
      chondrosarcomas allows radical removal with low morbidity rates and without
      mortality. Given the good long-term prognosis, surgical treatment should not
      deteriorate significantly patients' quality of life.

PMID- 18818962
TI  - On-line biomass estimation in biosurfactant production process by Candida
      lipolytica UCP 988.
AB  - Biomass is an important variable in biosurfactant production process. However,
      such bioprocess variable, usually, is collected by sampling and determined by off
      line analysis, with significant time delay. Therefore, simple and reliable on
      line biomass estimation procedures are highly desirable. An artificial neural
      network model (ANN) is presented for the on-line estimation of biomass
      concentration, in biosurfactant production by Candida lipolytica UCP 988, as a
      nonlinear function of pH and dissolved oxygen. Several configurations were
      evaluated while developing the optimal ANN model. The optimal ANN model consists
      of one hidden layer with four neurons. The performance of the ANN was checked
      using experimental data. The results obtained indicate a very good predictive
      capacity for the ANN-based software sensor with values of R2 of 0.969 and RMSE of
      0.021 for biomass concentration. Estimated biomass using the ANN was proved to be
      a simple, robust and accurate method.

PMID- 18818963
TI  - ERG evaluation of daily, high-dose sildenafil usage.
AB  - PURPOSE: Sildenafil can cause transient, mild ERG changes in healthy individuals
      taking large single doses. Although the drug was originally intended for
      intermittent use in erectile dysfunction, it has now been approved for chronic
      use in subjects with pulmonary arterial hypertension (PAH). The purpose of our
      study is to investigate possible ERG changes in subjects using large doses of
      sildenafil on a chronic daily basis. METHODS: We examined five subjects with PAH
      taking sildenafil daily for 1-4 years. Full-field electroretinogram (ERG),
      multifocal ERG (mfERG), and color testing were performed. Three of the subjects
      returned on a later date for challenge off and on the medication. RESULTS: On
      chronic daily sildenafil, color vision testing was normal, and ERG and mfERG
      amplitudes were normal; however, cone implicit times on drug were modestly
      lengthened. There were no consistent full-field ERG changes when off the drug,
      but the mfERG showed a small amplitude increase and implicit time decrease, which
      returned 1 h after re-dosing. CONCLUSION: There was a modest lengthening of cone
      implicit time on chronic daily doses of sildenafil and a hint that some of these
      changes may be reversible in the short term. It does not appear that chronic
      sildenafil usage at these dosage levels is seriously toxic or threatening to
      vision.

PMID- 18818964
TI  - Integrated testing and intelligent assessment-new challenges under REACH.
AB  - BACKGROUND, AIM AND SCOPE: Due to a number of drawbacks associated with the
      previous regime for the assessment of new and existing chemicals, the European
      Union established a new regulation concerning the registration, evaluation,
      authorisation and restriction of chemicals (REACH). All relevant industrial
      chemicals must now be assessed. Instead of the authorities, industry itself is
      responsible for the risk assessment. To achieve better and more efficient
      assessments while reducing animal testing, all information-standard, non-standard
      and non-testing-has to be used in an integrated manner. To meet these challenges,
      the current technical guidance documents for risk assessment of new and existing
      chemicals had to be updated and extended considerably. This was done by experts
      in a number of REACH Implementation Projects. This paper presents the most
      relevant results of the expert Endpoint Working Group on Aquatic Toxicity in
      order to illustrate the change of paradigm in the future assessment of hazards to
      the aquatic environment by chemical substances. MAIN FEATURES AND CHALLENGES:
      REACH sets certain minimum data requirements in order to achieve a high level of
      protection for human health and the environment. It encourages the assessor to
      use alternative information instead of or in addition to standard one. This
      information has to be equivalent to the standard information requirement and
      adequate to draw overall conclusions with respect to the regulatory endpoints
      classification and labelling, persistent, bioaccumulative and toxic (PBT)
      assessment and predicted no-effect concentrations (PNEC) derivation. The main
      task of the expert working group was to develop guidance on how to evaluate the
      toxicity of a substance based on integration of information from different
      sources and of various degrees of uncertainty in a weight of evidence approach.
      INTEGRATED TESTING AND INTELLIGENT ASSESSMENT: In order to verify the equivalence
      and adequacy of different types of information, a flexible sequence of steps was
      proposed, covering characterisation of the substance, analysis of modes of
      action, identification of possible analogues, evaluation of existing in vivo and
      in vitro testing data as well as of QSAR results. Finally, all available data
      from the different steps have to be integrated to come to an overall conclusion
      on the toxicity of the substance. This weight of evidence approach is the basis
      for the development of integrated testing strategies (ITS), in that the available
      evidence can help to determine subsequent testing steps and is essential for an
      optimal assessment. Its flexibility helps to meet the different requirements for
      drawing conclusions on the endpoints classification and labelling, PNEC
      derivation as well as PBT assessment. The integration of all kinds of additional
      information in a multi-criteria assessment reduces the uncertainties involved
      with extrapolation to the ecosystem level. The weight of evidence approach is
      illustrated by practical examples. CONCLUSIONS AND PERSPECTIVES: REACH leads to
      higher challenges in order to make sound decisions with fewer resources, i.e. to
      move away from extensive standard testing to an intelligent substance-tailored
      approach. Expert judgement and integrated thinking are key elements of the weight
      of evidence concept and ITS, potentially leading to better risk assessments.
      Important sub-lethal effects such as endocrine disruption, which are not covered
      by the current procedure, can be considered. Conclusions have to be fully
      substantiated: Risk communication will be an important aspect of future
      assessments.

PMID- 18818965
TI  - Regiospecific enzymatic oxygenation of cis-vaccenic acid in the marine
      phototrophic bacterium Erythrobacter sp. strain MG3.
AB  - The fatty acid composition of the marine phototrophic bacterium Erythrobacter sp.
      strain MG3 was analysed. The involvement of an unusual enzymatic peroxidation of
      the allylic carbon 10 of cis-vaccenic acid in this strain was confirmed. This
      process, which seems to be a characteristic of some aerobic and anaerobic
      phototrophic bacteria, appeared to also act on the allylic carbon 10 of octadeca
      5,11-dienoic acid. Enzymatic degradation of 10-hydroperoxyoctadec-11(cis)-enoic
      acid resulting from the peroxidation of cis-vaccenic acid mainly involves
      reduction to the corresponding hydroxy acid (probably catalysed by peroxygenases)
      and cleavage to the corresponding oxoacid, which is then biohydrogenated. Abiotic
      degradation of this hydroperoxide involves allylic rearrangement to 10
      hydroperoxyoctadec-11(trans)-enoic and 12-hydroperoxyoctadec-10(trans)-enoic
      acids and cyclisation to the very unusual 7,10-epoxyoctadec-11(cis)-enoic acid.
      Several tests carried out at different periods of growth and under different
      growth conditions allowed to show that the induction of this enzymatic
      peroxidation process strongly depends on the physiological state of the cells and
      is enhanced during C-limitation and at low temperatures.

PMID- 18818966
TI  - The major glycerophospholipids of the predatory and parasitic bacterium
      Bdellovibrio bacteriovorus HID5.
AB  - Bdellovibrio are small motile bacteria that attack and parasitize larger Gram
      negative bacteria and since they might have practical applications, these
      organisms are attracting the attention of researchers as indicated by the
      sequencing of the B. bacteriovorus genome. There is an earlier report showing
      that B. bacteriovorus scavenges fatty acids from the host cell during its
      parasitic phase otherwise the biochemical nature of its lipids, particularly its
      complex lipids, remains unknown. We here report on the phospholipid classes of an
      axenically cultured host-independent strain (HID5). Phospholipids and fatty acids
      were identified by a variety of chromatographic procedures and high-resolution
      mass spectrometric techniques. Phosphatidylethanolamine was the major
      phospholipid and phosphatidylserine, cardiolipin, phosphatidylglycerol, and N
      acylphosphatidylethanolamine were also identified. The major fatty acids were
      16:0, 16:1, 18:1, and 9,10-Mt C16:0 (cyC17:0). Unlike another predatory
      bacterium, Bacteriovorus stolpii strain UKi2, sphingolipids were not detected in
      B. bacteriovorus by the procedures used in this study. This is consistent with
      the apparent lack of genes coding for sphingolipid biosynthesis enzymes in the B.
      bacteriovorus genome database. The results are consistent with the separation of
      Bdellovibrio and Bacteriovorus into separate genera.

PMID- 18818967
TI  - Periampullary diverticula and technical success of endoscopic retrograde
      cholangiopancreatography.
AB  - INTRODUCTION/AIM: Periampullary diverticula (PAD) discovered incidentally during
      endoscopic retrograde cholangiopancreatography are usually asymptomatic, but can
      be a source of significant morbidity. The size of the diverticula and position of
      the papilla in relation to the diverticula are variable. The twofold aim of this
      study was to determine the prevalence of PAD in adult Indian patients and
      technical success of endoscopic retrograde cholangiopancreatography (ERCP).
      METHODS: Patients with PAD (group I) were prospectively entered into a database
      from May 2006 to May 2007. Diverticula were categorized based on size into small
      (<1.5 cm) and large (>1.5 cm). Papilla was arbitrarily defined as type A when
      located outside the diverticulum and type B when the position was
      intradiverticular. Requirement of needle knife papillotomy (NKP), sphincterotomy,
      and overall success/failure of the procedure were recorded. One hundred
      consecutive patients without PAD undergoing ERCP served as controls (group II).
      RESULTS: PAD were present in 46 (7.5%) of the 600 patients undergoing ERCP for
      various indications (group I). Mean age of patients with PAD (51 +/- 15 years)
      was significantly higher than control group (39 +/- 17 years) (p < 0.001). Of the
      46 diverticula, 26 diverticula (56.5%) were large. In small diverticula, the
      papilla was extradiverticular (type A) in all 20 (100%) patients, whereas in the
      group with diverticula >1.5 cm only 57% was extradiverticular. Successful
      cannulation was achieved in 97% (45/46). NKP was done in six patients, five of
      whom had type A papilla. There was a significant high rate of NKP inpatients
      without PAD compared with patients with PAD (p = 0.001), whereas the rate of
      endoscopic papillotomy (EPT) was similar in both groups. Complete common bile
      duct (CBD) clearance was achieved in 93% patients in PAD group as compared with
      96% in the non-PAD group (p = nonsignificant). Complications after ERCP were
      similar in both groups. CONCLUSION: PAD were present in 7.5% of patients. Fifty
      six percent of PAD were large and in the vast majority (76%) papilla was
      extradiverticular in location. PAD were not associated with an increased risk of
      EPT-related complications.

PMID- 18818968
TI  - Percutaneous fetoscopic patch closure of human spina bifida aperta: advances in
      fetal surgical techniques may obviate the need for early postnatal neurosurgical
      intervention.
AB  - BACKGROUND: A percutaneous minimally invasive fetoscopic approach was attempted
      for closure of a spina bifida aperta in two fetuses with L5 lesions. The goal was
      to obviate the need for postnatal neurosurgery to manage this condition. METHODS
      AND RESULTS: The percutaneous fetoscopic procedures were performed by a two-layer
      approach at respectively 22+/-2 and 22+/-4 weeks of gestation. The fetuses were
      delivered respectively at 32+/-6 and 32+3 weeks of gestation. Their neural cords
      were completely covered although in small areas skin closure was incomplete.
      Postnatally, complete skin closure occurred beneath an occlusive draping within 2
      to 3 weeks such that neurosurgical intervention was not required. Both neonates
      showed reversal of hindbrain herniation, near-normal leg function, and
      satisfactory bladder and bowel function. For one of the two fetuses,
      ventriculoperitoneal shunt insertion was not required. CONCLUSIONS: Percutaneous
      minimally invasive fetoscopic patch closure of spina bifida aperta offers a
      substantially less maternal trauma than open fetal surgical repair and currently
      may even obviate the need for postnatal neurosurgical repair. With a little
      further improvement in surgical techniques and a better understanding of
      incorporating surgical patches into the fetus, complete skin closure seems
      possible in the near future.

PMID- 18818969
TI  - Investigation of phosphorylation site responsible for CaLP (P. fucata) nucleo
      cytoplasmic shuttling triggered by overexpression of p21Cip1.
AB  - Calmodulin (CaM) is a highly conserved and ubiquitous Ca(2+)-binding protein
      regulating intracellular Ca(2+) concentration by acting as a sensor of this
      divalent cation in eukaryotic cells. Being such a very important signal sensor,
      CaM is susceptible to undergo many posttranslational modifications. One of these
      important modifications is its phosphorylation. Our previous investigations
      showed that CaM and calmodulin-like protein (CaLP) cloned from Pinctada fucata
      have many different characteristics in spite of their high similarity to each
      other. We have narrowed down that the C-terminal domains of CaM and CaLP are
      responsible for their discrepant subcellular localizations and shuttling of CaLP
      when it is co-transfected with p21(Cip1), which is commonly considered as an
      important cell cycle regulating protein. In this study, we first predicted the
      potential phosphorylation site responsible for the shuttling and confirmed by
      fluorescence confocal microscopy. Together with fluorescence activated cell
      sorter analysis, we further investigated the releasing ability of wild type and
      point mutated CaLP from arrested cell cycle caused by p21(Cip1) overexpression.
      By performing pull-down analysis and phosphorylation status of CaLP in cytoplasm
      fraction of transfected COS-7 cells with CaLP alone and phosphorylation status of
      CaLP in nuclear fraction of co-transfected COS-7 cells with CaLP and p21(Cip), we
      propose that the CaLP staying in the cytoplasm is in the state of
      phosphorylation, but when p21(Cip1) is overexpressed in mammalian cells, some
      signal triggers CaLP dephosphorylation and translocation into the nucleus.

PMID- 18818970
TI  - Trade-off between sensitivity and specificity in the cabbage looper moth response
      to sex pheromone.
AB  - The evolution of male moth responses to pheromone blends may be constrained by a
      trade-off between two response traits: sensitivity and breadth of response.
      Population genetic simulations predict that if sensitivity and breadth of
      response are negatively correlated (i.e., a trade-off exists), then selection
      will favor males with narrow response phenotypes and high sensitivity. Although
      sensitivity-breadth of response trade-offs are generally assumed to exist and are
      implicit to the shape of male preference function, this study is the first to
      provide empirical support measuring behavior at the level of the individual.
      Previous studies with the cabbage looper, Trichoplusia ni, have documented the
      existence of a mutant pheromone strain. While mutant females produce a pheromone
      blend significantly different from wild-type females, mutant males respond
      equally to the wild-type and mutant pheromone blends. This study used wind tunnel
      bioassays to document that relative to wild-type males, mutant males had broader
      response profiles but lower pheromone sensitivity. While wild-type male responses
      were highest to the wild-type pheromone blend, mutant males did not discriminate
      among pheromone blends. These results are consistent with a trade-off between
      breadth of response and sensitivity. Pure wild-type and mutant lines were crossed
      and hybrid males assayed. Both hybrid types (maternal wild-type and maternal
      mutant hybrids) responded similarly. Hybrid males had response profiles similar
      to wild-type males and the reduced sensitivity observed in mutant males. These
      results suggest a possible hybrid disadvantage and a putative mechanism for
      reinforcement of male pheromone response traits.

PMID- 18818971
TI  - Expression and secretion of endostatin in thyroid cancer.
AB  - BACKGROUND: In thyroid cancer (TC) endostatin was identified as a powerful
      negative regulator of tumor angiogenesis in vitro. It is currently being
      evaluated in phase I trials for antiangiogenic therapy in various solid tumors.
      The aim of this study was to evaluate endostatin expression in archival TC
      specimens and its secretion following stimulation with thyrotropin (TSH) and
      epidermal growth factor (EGF) in TC cell lines. METHODS: Tissue microarrays of 44
      differentiated and 7 anaplastic TC and their metastasis were immunostained for
      endostatin protein expression and compared with corresponding non-neoplastic
      thyroid tissue (NT). In vitro, six differentiated (FTC133, FTC236, HTC, HTC-TSHr,
      XTC, and TPC1) and three anaplastic (C643, Hth74, Kat4.0) TC cell lines were
      evaluated for basal as well as TSH (1-100 mU/ml) and EGF stimulated (1-100 ng/ml)
      endostatin. RESULTS: Endostatin was detected in all TC and more than half of the
      NT. Endostatin expression was more frequent and intense in differentiated as
      compared to anaplastic TC. In vitro, basal endostatin secretion varied between 33
      +/- 5 pg/ml (FTC236) and 549 +/- 65 pg/ml (TPC1) and was doubled in FTC, when the
      "primary" (FTC133) was compared with the metastasis (FTC236). Some cell lines
      showed TSH-induced (e.g., 60% in XTC) or EGF-induced (e.g., 120% in TPC1)
      upregulation of endostatin secretion, while others did not, despite documented
      receptor expression. CONCLUSION: This study demonstrates endostatin expression in
      TC, metastasis and--less frequently and intensely--in NT, suggesting a possible
      association to tumor progression. In vitro, endostatin secretion of some cell
      lines is regulated by TSH and EGF, however the individual differences deserve
      further functional studies. These results support rather tumor-specific than
      histotype-specific expression and regulation of endostatin in TC.

PMID- 18818972
TI  - Multiscale modeling of fluid transport in tumors.
AB  - A model for fluid flow through the leaky neovasculature and porous interstitium
      of a solid tumor is developed. A network of isolated capillaries is analyzed in
      the limit of small capillary radius, and analytical expressions for the hydraulic
      conductivities and fractional leakage coefficients derived. This model is then
      homogenized to give a continuum description in terms of the vascular density. The
      resulting equations comprise a double porous medium with coupled Darcy flow
      through the interstitium and vasculature.

PMID- 18818973
TI  - Estimating the total rate of DNA replication using branching processes.
AB  - Increasing the knowledge of various cell cycle kinetic parameters, such as the
      length of the cell cycle and its different phases, is of considerable importance
      for several purposes including tumor diagnostics and treatment in clinical health
      care and a deepened understanding of tumor growth mechanisms. Of particular
      interest as a prognostic factor in different cancer forms is the S phase, during
      which DNA is replicated. In the present paper, we estimate the DNA replication
      rate and the S phase length from bromodeoxyuridine-DNA flow cytometry data. The
      mathematical analysis is based on a branching process model, paired with an
      assumed gamma distribution for the S phase duration, with which the DNA
      distribution of S phase cells can be expressed in terms of the DNA replication
      rate. Flow cytometry data typically contains rather large measurement variations,
      however, and we employ nonparametric deconvolution to estimate the underlying DNA
      distribution of S phase cells; an estimate of the DNA replication rate is then
      provided by this distribution and the mathematical model.

PMID- 18818976
TI  - Depressive symptoms among older adults in Mexico City.
AB  - BACKGROUND: Ageing and depression are associated with disability and have
      significant consequences for health systems in many other developing countries.
      Depression prevalence figures among the elderly are scarce in developing
      countries. OBJECTIVE: To estimate the prevalence of depressive symptoms and their
      cross-sectional association with selected covariates in a community sample of
      Mexico City older adults affiliated to the main healthcare provider. DESIGN:
      Cross-sectional, multistage community survey. PARTICIPANTS: A total of 7,449
      persons aged 60 years and older. MEASUREMENTS: Depression was assessed using the
      30-item Geriatric Depression Scale (GDS); cognitive impairment, using the Mini
      Mental State Examination; and health-related quality of life with the SF-36
      questionnaire. MAIN RESULTS: The prevalence of significant depressive symptoms
      was estimated to be 21.7%, and 25.3% in those aged 80 and older. After correcting
      for GDS sensitivity and specificity, major depression prevalence was estimated at
      13.2%. Comparisons that follow are adjusted for age, sex, education and stressful
      life events. The prevalence of cognitive impairment was estimated to be 18.9% in
      depressed elderly and 13.7% in non-depressed. SF-36 overall scores were 48.0 in
      depressed participants and 68.2 in non-depressed (adjusted mean difference = 
      20.2, 95% CI = -21.3, -19.1). Compared to non-depressed elderly, the odds of
      healthcare utilization were higher among those depressed, both for any health
      problem (aOR 1.4, 95% CI = 1.1, 1.7) and for emotional problems (aOR 2.7, 95% CI
      = 2.2, 3.2). CONCLUSIONS: According to GDS estimates, one of every eight Mexican
      older adults had major depressive symptoms. Detection and management of older
      patients with depression should be a high priority in developing countries.

PMID- 18818977
TI  - Percutaneous endoscopic gastrostomy tube placement is safe in patients undergoing
      corticosteroid therapy.
AB  - BACKGROUND: Percutaneous endoscopic gastrostomy tube placement is performed
      commonly in patients unable to eat. Corticosteroids have been shown to increase
      the incidence of infections in patients undergoing surgical gastrostomy. The
      safety of percutaneous endoscopic gastrostomy in patients receiving
      corticosteroids has not been demonstrated. METHODS: A retrospective review of 746
      patients undergoing percutaneous endoscopic gastrostomy at a single institution
      between January 2002 and June 2007 was performed. Patients receiving
      corticosteroid therapy either acutely or chronically were identified. Charts were
      reviewed for demographic information, diagnoses, comorbidities, complications,
      and death. RESULTS: Seven hundred forty-six patients underwent percutaneous
      endoscopic gastrostomy tube placement of which only 745 charts were complete and
      available for review. Ninety-four patients (12.6%) were receiving steroids at the
      time of the procedure. Fifty-nine patients (7.9%) received steroids for two or
      less weeks (acute), and 35 patients (4.5%) received steroids for more than 2
      weeks (chronic). The overall incidence of complications was 98/745 (13.3%). No
      significant difference in post-procedural complications occurred in patients not
      receiving steroids 83/651 (12.7%) and steroid recipients 15/94 (16.0%). There was
      no difference in complications between the acute steroid group 10/59 (16.9%) and
      the chronic steroid group 5/35 (14.3%). CONCLUSIONS: Percutaneous endoscopic
      gastrostomy tube placement may be safely performed in patients receiving
      corticosteroids both acutely and chronically with complication rates comparable
      to those patients not receiving steroid medications.

PMID- 18818978
TI  - Laparoscopic treatment of celiac artery compression syndrome: case series and
      review of current treatment modalities.
AB  - INTRODUCTION: Compression of the celiac artery by the diaphragmatic crura, the
      median arcuate ligament, or the fibrous periaortic ganglionic tissue results in a
      rare constellation of symptoms known as celiac artery compression syndrome
      (CACS). ANATOMY: First described in 1963 by Harjola in a patient with symptoms of
      mesenteric ischemia, it remains an elusive diagnosis. CLINICAL PRESENTATION:
      Patients commonly present with a wide variety of symptoms resulting in multiple
      diagnostic tests. DIAGNOSIS: A firm diagnosis is difficult to establish, and
      treatment is equally challenging. These challenges are illustrated by the
      following case series, and evidence supporting current treatment modalities is
      reviewed. TREATMENT: We describe a laparoscopic approach to decompression of the
      celiac artery facilitated by intraoperative ultrasound.

PMID- 18818979
TI  - Leiomyomatosis of the esophagus: experience over a decade.
AB  - PURPOSE: To assess the clinical, radiological findings, and treatment strategies
      in patients with esophageal leiomyomatosis. BACKGROUND: Esophageal leiomyomatosis
      is a rare hamartomatous disorder with varied presentation. It is described mostly
      in children and is associated with Alport's syndrome. METHODS: A retrospective
      analysis of three cases managed in the Department of General Surgery at
      Chandigarh over a period of 10 years. RESULTS: The study involves three female
      patients of different generations within the same family with age range of 10-58
      years. All presented with dysphagia of 2-7 years duration. Barium swallow
      revealed a long-segment stricture in two patients. Computed tomography (CT)
      demonstrated a circumferential mass lesion in the lower esophagus in all the
      patients. Esophageal resection was carried out in all the patients. All patients
      made an uneventful recovery. CONCLUSIONS: Esophageal leiomyomatosis should be
      suspected in patients with long-standing dysphagia. Barium findings are
      suggestive but can mimic achalasia. CT scan shows a circumferential esophageal
      wall thickening. Surgical resection and reconstruction of the digestive passage
      is the optimal treatment.

PMID- 18818980
TI  - Five-year follow-up after laparoscopic Roux-en-Y gastric and partial ileal bypass
      for treatment of morbid obesity and uncontrolled hyperlipidemia.
AB  - BACKGROUND: Morbid obesity is associated with significant co-morbid illnesses and
      mortality. Hyperlipidemia is strongly associated with atherosclerosis and
      cardiovascular disease. Laparoscopic Roux-en-Y gastric bypass (LRYGB) is a proven
      and effective procedure for the treatment of morbid obesity and its related co
      morbid illnesses. In a randomized prospective clinical trial, partial ileal
      bypass showed sustained control of hyperlipidemia and reduced comorbidities.
      Given risks of surgery, pharmacologic agents are the current primary therapy for
      hyperlipidemia. However, a morbidly obese patient with medically refractory
      hyperlipidemia may benefit from a combined laparoscopic Roux-en-Y gastric bypass
      and partial ileal bypass. We are describing the first case of a totally
      laparoscopic approach. METHODS: A 56-year-old female patient with morbid obesity
      (BMI 45.2 kg/m(2)) and medically refractive hyperlipidemia underwent a combined
      LRYGB and partial ileal bypass in 2002. She was continuously followed for 5 years
      for weight profile, hyperlipidemia, post-operative complications, and morbidity.
      RESULTS: Five-year follow-up of the patient showed sustained excess body weight
      loss. Her lipid profile has approached normal ranges with less medication. She
      experienced no comorbidities related to surgery or hyperlipidemia. CONCLUSIONS:
      Laparoscopic Roux-en-Y gastric bypass and partial ileal bypass may be the best
      option for the patient who has morbid obesity and medically refractory
      hyperlipidemia and should be considered for select patients.

PMID- 18818981
TI  - Local recurrence of disease after unplanned excisions of high-grade soft tissue
      sarcomas.
AB  - Unplanned excisions of soft tissue sarcomas occur with alarming frequency and
      result in high rates of residual disease, potentially affecting patient
      prognosis. To determine if unplanned excisions and residual disease status at
      tumor bed excision increased local recurrence rates and predicted disease
      specific patient survival, we retrospectively reviewed 203 consecutive patients
      with high-grade soft tissue sarcomas treated operatively and followed for at
      least 2 years (mean, 4.8 years) or until patient death. Among the 64 patients
      (32%) who had undergone previous unplanned excisions, six had gross residual
      disease and 40 of the remaining 58 (69%) had microscopic residual disease in the
      tumor bed. We observed subsequent local recurrence in nine of the 139 patients
      (6%) after planned excision compared with 22 patients (34%) after unplanned
      excision. More patients with unplanned excisions who underwent limb salvage
      procedures required flap coverage and/or skin grafting with their definitive
      resection (30% versus 5%). In the unplanned excision cohort, residual disease
      status at tumor bed excision predicted increased rates of local recurrence and
      decreased disease-specific survival. Unplanned excisions of high-grade soft
      tissue sarcomas resulted in increased rates of local recurrence but not disease
      specific survival. Residual disease at reexcision predicted the likelihood of
      local recurrence. LEVEL OF EVIDENCE: Level II, prognostic study. See the
      Guidelines for Authors for a complete description of levels of evidence.

PMID- 18818982
TI  - Papers presented at the Hip Society Meetings 2008: editorial comment.

PMID- 18818983
TI  - In vitro assays for the evaluation of drug resistance in tumor cells.
AB  - Oncologic diseases are among leading cause of mortality in developed countries.
      Despite significant progress, the use of standard cytotoxic chemotherapy has
      reached a therapeutical plateau. Currently, the process of selecting chemotherapy
      represents a trial and error method neglecting biological individuality of tumor
      and its bearer. The improvement of treatment results is expected from ex vivo
      drug sensitivity testing which may allow to choose the most effective drug for
      individual patient and to exclude agents to which the tumor cells exert
      resistance. New techniques and rapidly increasing knowledge about the molecular
      basis of malignant diseases provide important opportunities for the future of
      chemotherapy. This paper reviews current methods used to test the resistance of
      tumor cells to a panel of anticancer agents in vitro. In addition, we focused on
      the in vitro MTT assay which represents one of major technique for testing of
      tumor cell resistance to anticancer agents.

PMID- 18818984
TI  - Routine ultrasound-guided liver biopsy versus echo-assisted procedure in viral
      chronic hepatitis.
AB  - PURPOSE: Ultrasound (US)-assisted liver biopsy is the most widespread practice
      for the staging of chronic hepatitis, but there are no data about a comparison
      with the US-guided procedure in terms of safety and diagnostic yield. The aim of
      this study was a retrospective analysis about 357 biopsies performed by using
      both these techniques. MATERIALS AND METHODS: We analysed 176 US-guided biopsies
      and and 181 US-assisted liver biopsies performed in the same unit in patients
      with chronic viral hepatitis. We recorded the number of passes, sample
      fragmentation and sample size, number of portal spaces and degree of fibrosis.
      Mortality and morbidity were also assessed. Differences between the two groups of
      needle biopsies were analysed statistically by the Welch test, with significance
      at p<0.05. RESULTS: Specimens obtained by US-guided liver biopsy were 27 mm long
      (range 25-28.9 mm) versus 13 mm mean value (range 12.2-13.9 mm, p<0.0001) of
      samples from US-assisted liver biopsies and contained 15.7 portal tracts (range
      14.7-16.7) versus 11 mean value (range 10-11.9, p<0.0001) of specimens obtained
      by echo-assisted needle biopsy. Mortality and major complication rate was zero in
      our series. Both groups of liver biopsies were comparable with respects to number
      of passes and sample fragmentation. CONCLUSIONS: Both methods showed overlapping
      security. The diagnostic yield seems to be greater if liver biopsy is performed
      by the echo-guided technique.

PMID- 18818985
TI  - Advantages of multidetector-row CT with multiplanar reformation in guiding
      percutaneous lung biopsies.
AB  - PURPOSE: This study aimed to assess the usefulness of multiplanar reformations
      (MPR) during multidetector-row computed tomography (MDCT)-guided percutaneous
      needle biopsy of lung lesions difficult to access with the guidance of the native
      axial images alone owing to overlying bony structures, large vessels or pleural
      fissures. MATERIALS AND METHODS: MDCT-guided transthoracic needle biopsy (TNB)
      was performed on 84 patients (55 men and 29 women; mean age 65 years) with
      suspected lung neoplasm by using a spiral MDCT scanner with the simultaneous
      acquisition of six slices per rotation. We determined the site of entry of the 22
      gauge Chiba needle on native axial images and coronal or sagittal MPR images. We
      took care to ensure the shortest needle path without overlying large vessels,
      main bronchi, pleural fissures or bony structures; access to the lung parenchyma
      as perpendicular as possible to the pleural plane; and sampling of highly
      attenuating areas of noncalcified tissue within the lesion. RESULTS: Diagnostic
      samples were obtained in 96% of cases. In 73 patients, lesions appeared as a
      solid noncalcified nodule <2 cm; 11 lesions were mass-like. In 22, the biopsy
      required MPR guidance owing to overlying ribs (18), fissures (2) or hilar
      mediastinal location (2). CONCLUSIONS: MDCT MPR images allowed sampling of
      pulmonary lesions until now considered unreachable with axial MDCT guidance
      because of overlying bony structures (ribs, sternum and scapulae) or critical
      location (hilar-mediastinal, proximity to the heart or large vessels). Compared
      with the conventional procedure, the use of MPR images does not increase the rate
      of pneumothorax or the procedure time.

PMID- 18818986
TI  - Prognostic relevance of serum levels and cellular expression of adiponectin in B
      cell chronic lymphocytic leukemia.
AB  - The correlation between well-established biological parameters of prognostic
      relevance in B-cell chronic lymphocytic leukaemia (CLL) [i.e., mutational status
      of the immunoglobulin heavy chain variable region (IgV(H)), ZAP-70- and CD38
      expression] and adiponectin serum concentration was evaluated in a cohort of 69
      previously untreated Binet stage A CLL patients. Adiponectin levels inversely
      correlated with absolute peripheral blood lymphocyte count (r = -0.254; P =
      0.03), CD38-positive CLL cells (r = -0.294; P = 0.04) and ZAP-70 (r = -0.285; P =
      0.03). The univariate Cox proportional hazard model demonstrated that, in
      addition with lower serum levels of adiponectin (P = 0.01), the unmutated IgV(H)
      condition (P = 0.002) and ZAP-70-positivity (P = 0.02) were associated with a
      shorter time to first treatment (TFT). However, in multivariate analysis only ZAP
      70 positivity emerged as predictor of the TFT (P = 0.008). The levels of
      adiponectin in CLL were evaluated in 60 patients from an independent cohort
      investigated by gene expression profiling. Adiponectin gene expression was
      invariably low suggesting a limited (if any) role of leukemic cells in the
      production of circulating adiponectin levels. In contrast, both adiponectin
      receptor 1 (AdipoR1) and AdipoR2 mRNA were highly expressed by CLL cells with a
      degree of inter-patient variability. Our results, although preliminary, lend
      support to the idea that adiponectin secretion by bone marrow adipocytes might
      represent a possible promising drug target in the field of hematology.

PMID- 18818987
TI  - Whole-breast volume perfusion images using 256-row multislice computed
      tomography: visualization of lesions with ductal spread.
AB  - BACKGROUND: The aim of this study was to apply perfusion techniques to breast
      tumors using a prototype 256-row multislice computed tomography (CT) scanner
      (which allows a wide range of 128 mm to be scanned and can provide whole-breast
      perfusion maps without any dead angles) to improve contrast and assess the
      possibility of precisely depicting the extent of breast cancer. PATIENTS AND
      METHODS: The study group included seven patients with breast cancer who were
      scheduled to undergo radical surgery and radiotherapy. Dynamic scanning was
      performed using a 256-row multislice CT scanner during normal respiration. Volume
      perfusion images of the entire breast were obtained using the maximum slope
      method. Perfusion map images and early-phase breast CT images at 54 s were
      compared by means of pathological examination. RESULTS: All breast cancers could
      be distinguished from normal mammary glands based on the perfusion value. The
      extent of cancer depicted in perfusion images showed excellent agreement with the
      pathology findings for invasive ductal carcinoma and ductal carcinoma in situ. In
      three patients, all ductal spread, parts of which were not visualized by early
      phase CT, were depicted in volume perfusion images. Simulation analysis suggested
      that perfusion maps could be generated with fewer scanning points. CONCLUSION:
      The results of the present study suggest that volume perfusion imaging may be
      useful for depicting the extent of breast cancer, with excellent sensitivity.
      Further research is needed to determine the clinical relevance of these findings.

PMID- 18818988
TI  - Minimally invasive technology in the management of breast disease.
AB  - Minimally invasive surgery is gaining popularity around the world because it
      achieves the same or even superior results when compared to standard surgery but
      with less morbidity. Minimally invasive breast surgery is a broad concept
      encompassing new developments in the field of breast surgery that work on this
      minimally invasive principle. In this regard, breast-conserving surgery and
      sentinel lymph node biopsy are good illustrations of this concept. There are
      three major areas of progress in the minimally invasive management of breast
      disease. First, percutaneous excisional devices are now available that can
      replace the surgical excision of breast mass lesions. Second, various ablative
      treatments are capable of destroying breast cancers in situ instead of surgical
      excision. Third, mammary ductoscopy provides a new approach to the investigation
      of mammary duct pathology. Clinical experience and potential applications of
      these new technologies are reviewed.

PMID- 18818989
TI  - Estrogen signaling pathway and hormonal therapy.
AB  - Hormonal therapy, such as estrogen-targeting therapy, has undergone remarkable
      development in recent several years, using drugs such as LH-RH agonists, new
      SERMs and third-generation aromatase inhibitors. Several ongoing large-scale
      international clinical trials for hormonal therapy are establishing the standard
      protocol for treatments with these drugs. On the other hand, there have been
      attempts to predict the individual efficacy of hormonal therapy using classical
      molecular biomarkers such as ER and PgR. However, approximately one-third of
      ERalpha-positive patients do not respond to endocrine therapy, while some ERalpha
      negative patients are responsive. These discrepancies may be due to the different
      estrogen-related intracellular signaling pathways in breast cancer cells.
      Furthermore, the ineffectiveness of hormonal therapy in some individuals (due to,
      for example, aromatase inhibitor resistance) may be caused by these mechanisms.
      In this paper, we discuss the molecular mechanisms of these different responses
      to hormonal therapies and their implications for the estrogen signaling pathway
      in breast cancer cells. Furthermore, we touch upon basic studies into predicting
      the efficacy of hormonal therapy and new strategies in this field.

PMID- 18818990
TI  - Filterless fluorometry with enhanced sensitivity.
AB  - We describe a novel approach for fluorometry with light-emitting-diodes (LEDs) as
      excitation source that capitalizes on the principle of light shielding and total
      internal reflection to operate without optical filters. This scheme is
      practicable, demonstrated to significantly reduce the amount of excitation light
      overlapping the fluorescence signals at the photodetector, operated best with
      excitation light applied orthogonal to detection, and permitted higher
      measurement sensitivity of fluorophore emission.

PMID- 18818991
TI  - The other side of the healthy immigrant paradox: Chinese sojourners in Ireland
      and Britain who return to China due to personal and familial health crises.
AB  - Based on participant observation and interviews conducted between 2003 and 2006,
      this paper examines the experiences of three young adult Chinese sojourners in
      Ireland and the United Kingdom who return to the People's Republic of China for
      permanent residence because of personal or familial health crises. Their
      experiences illustrate the plight of failed sojourners who are part of the little
      studied other side of the "healthy immigrant paradox." The experiences of the
      sojourners in this case study illustrate factors that tend to prevent less
      healthy or resourceful sojourner families from even entering the immigrant
      category, which has been shown to be paradoxically healthier than nonimmigrant
      native categories in epidemiological studies. This paper's approach demonstrates
      how ethnography can contribute to the study of public health by shedding light on
      the experiences of marginal individuals who fall between the cracks of
      epidemiological studies.

PMID- 18818992
TI  - Japan's hidden youths: mainstreaming the emotionally distressed in Japan.
AB  - One of the most talked-about social issues in Japan in recent years has been the
      problem of the nation's purportedly one million "hidden" youths, known as
      hikikomori (literally, "the withdrawn"). Most observers agree that the category
      of hikikomori encompasses a wide range of problems and provocations. The fact
      that these various dilemmas lead to the shared outcome of shutting oneself away
      at home is the point of departure here. The article explores the spheres of
      mental health care, education and family, focusing on the reluctance to highlight
      underlying psychological dimensions of hikikomori and the desire on the part of
      schools and families to "mainstream" Japanese children, accommodating as many as
      possible within standardized public education. Hikikomori can perhaps be seen as
      a manifestation of Japanese democracy, in which the good society is imagined as
      cohesive, protective and secure, rather than one in which the individual can
      freely exercise the right to be different. Schools, families and the sphere of
      mental health care have focused on producing social inclusion but have
      discouraged citizens from being labeled as "different" -- even when such a
      distinction might help them. The dearth of facilities and discourse for caring
      for the mentally ill or learning disabled is, in many respects, the darker side
      of Japan's successes. Those who cannot adjust are cared for through the
      institutions of families, companies and various other spheres that offer spaces
      to rest and to temporarily "drop out"; however, the expectation is that rest will
      eventually lead to a re-entry into mainstream society. Often the psychological
      problem or disability that led to the problem goes unnamed and untreated
      (hikikomori, psychiatry, special education, youth, family, Japan).

PMID- 18818993
TI  - Correlates of joining a sexual harassment class action.
AB  - Researchers have proposed a variety of factors that influence the decision to
      seek legal relief in response to sexual harassment, but have generally failed to
      test these proposals empirically. The present study aims to address this gap by
      investigating the decision to join a class-action lawsuit. Participants were
      female professionals at a nationally based financial services firm, who either
      participated in or opted out of a sexual harassment class-action proceeding
      against the company. Five variables emerged as significant correlates of joining
      the class: organizational climate, turnover, financial dependence, PTSD, and
      primary appraisal. Dominance analysis identified contextual factors as the most
      important correlate. Theoretical and practical implications for the role of these
      factors in joining a class action are discussed.

PMID- 18818994
TI  - Pregnancy associated smoking behavior and six year postpartum recall.
AB  - BACKGROUND: This study examined predictors and behaviors of pregnancy-related
      smoking among women who belonged to a private health maintenance organization and
      the recall accuracy of pregnancy-related smoking behaviors after 6-years.
      METHODS: A cohort of 725 pregnant women was followed for six years. Major
      predictors for smoking behavior before, during, and one-year following pregnancy
      were determined. In addition, accuracy of recall six years postpartum of smoking
      behavior at the time of pregnancy and one-year postpartum was tested. RESULTS:
      Mother's education, asthma status, amount of pre-pregnancy smoking, gravidity,
      and father's smoking status were important in the prediction of pregnancy
      associated smoking. Agreement for recall of smoking behavior during pregnancy (6
      year recall) and one-year postpartum (5 year recall) were 90% and 91%,
      respectively. CONCLUSIONS: Despite potentially adverse outcomes, a proportion of
      women continue to smoke throughout pregnancy. A number of variables proved to be
      important predictors of pregnancy associated smoking behavior. These factors
      should be considered by smoking cessation programs targeting women of
      reproductive age. Additionally, there was substantial agreement for maternal
      recall at six years postpartum of smoking behavior at the time of pregnancy and
      one-year postpartum. This should be considered in retrospective study designs
      that are primarily based on maternal recall of smoking behaviors before, during,
      and following pregnancy.

PMID- 18818995
TI  - Maternal weight gain during pregnancy and child weight at age 3 years.
AB  - OBJECTIVES: To determine the importance of pregnancy weight gain as a predictor
      of overweight (Body Mass Index [BMI] >85th percentile) in offspring at age 3
      years and if its influence varies by maternal BMI. METHODS: Chi-square and
      logistic regression analyses were conducted on a sample of 208 mother-child pairs
      from an earlier observational cohort study on postpartum weight retention.
      RESULTS: In the final reduced regression model, maternal early pregnancy BMI was
      positively and significantly associated with overweight in offspring, as were
      birth weight above the sample median of 3,600 g and maternal smoking during
      pregnancy (P < or = 0.01). In addition, a significant interaction was found
      between maternal BMI and gestational weight gain (P = 0.03). The risk of
      offspring overweight that is associated with 5 excess pounds of net pregnancy
      weight gain increases with maternal BMI. CONCLUSIONS: Excess pregnancy weight
      gain is associated with increased risk of child overweight at age 3 years and its
      impact is greater among high and obese BMI women than it is in normal BMI women.
      Reducing maternal BMI in the preconception period in overweight women and
      preventing excessive weight gain in pregnancy for all women appear to be
      appropriate strategies to address the childhood obesity epidemic.

PMID- 18818996
TI  - Affect regulation, social context, and sexual intercourse in adolescents.
AB  - This study examined trajectories of positive and negative affect surrounding
      penile-vaginal sexual intercourse (sex) in adolescents and explored the influence
      of companionship on these trajectories. Using a handheld computer, sexually
      active adolescents (N = 67) reported momentary affect and sex events in response
      to several random signals each day for 1 week (1,777 reports, 266 sex events).
      Cubic spline regression analyses showed that positive affect began to increase
      before sex, peaked at the time sex was reported, and then returned to baseline.
      Negative affect did not differ from baseline before sex, but decreased following
      sex. Improvement in affect before and after sex varied according to
      companionship. Understanding the complex associations of affect, companionship,
      and sex has implications for interpreting and intervening on adolescent sexual
      behavior in social context.

PMID- 18818997
TI  - Intentional abstinence among homeless and unstably housed persons living with
      HIV/AIDS.
AB  - Some persons living with HIV/AIDS (PLWHA) engage in periods of sexual abstinence.
      Baseline data from a larger study of homeless/unstably housed PLWHA indicated
      that 20% (125/644) intentionally abstained from sex in the past 90 days. Reasons
      included: (1) 'not interested' (n = 78); (2) did not want to infect someone (n =
      46); and (3) did not have a partner (n = 37). Abstinence was less likely among
      all who had a main partner. Among men who have sex with men (MSM), abstinence was
      less likely among those with a detectable viral load. It was more likely among
      heterosexual men who were experiencing current housing problems and who had at
      least a high school education. Among women, abstinence was less likely among
      African Americans and those whose social networks were more aware of their HIV
      status. Better understanding of motivations to abstain may improve how programs
      serving PLWHA address this issue.

PMID- 18818998
TI  - Gay men who engage in group sex are at increased risk of HIV infection and onward
      transmission.
AB  - Among 746 participants in the Three or More Study (TOMS) of gay men who engaged
      in group sex in the previous 6 months, 22.4% reported unprotected anal
      intercourse (UAI) with any partners they did not know to be the same HIV
      serostatus as themselves. Not knowing oneself to be HIV-negative, not having a
      clear intention to use condoms, and more frequent group sex were independently
      associated with UAI. This study shows that gay men who engage in group sex
      represent an important priority for targeted HIV prevention activities and
      research.

PMID- 18818999
TI  - Contribution of position alpha4S336 on functional expression and up-regulation of
      alpha4beta2 neuronal nicotinic receptors.
AB  - Phosphorylation of the nicotinic acetylcholine receptor (nAChR) is believed to
      play a critical role in its nicotine-induced desensitization and up-regulation.
      We examined the contribution of a consensus PKC site in the alpha4 M3/M4
      intracellular loop (alpha4S336) on the desensitization and up-regulation of
      alpha4beta2 nAChRs expressed in oocytes. Position alpha4S336 was replaced with
      either alanine to abolish potential phosphorylation at this site or with aspartic
      acid to mimic phosphorylation at this same site. Mutations alpha4S336A and
      alpha4S336D displayed a threefold increase in the ACh-induced response and an
      increase in ACh EC(50). Epibatidine binding revealed a three and sevenfold
      increase in surface expression for the alpha4S336A and alpha4S336D mutations,
      respectively, relative to wild-type, therefore, both mutations enhanced
      expression of the alpha4beta2 nAChR. Interestingly, the EC(50)'s and peak
      currents for nicotine activation remained unaffected in both mutants. Both
      mutations abolished the nicotine-induced up-regulation that is normally observed
      in the wild-type. The present data suggest that adding or removing a negative
      charge at this phosphorylation site cannot be explained by a simple
      straightforward on-and-off mechanism; rather a more complex mechanism(s) may
      govern the functional expression of the alpha4beta2 nAChR. Along the same line,
      our data support the idea that phosphorylation at multiple consensus sites in the
      alpha4 subunit could play a remarkable role on the regulation of the functional
      expression of the alpha4beta2 nAChR.

PMID- 18819000
TI  - CCND1 G870A polymorphism contributes to breast cancer susceptibility: a meta
      analysis.
AB  - Cyclin D1 (CCND1), a key cell cycle regulatory protein that governs the cell
      cycle progression from G1 to S phase, can promote cell proliferation or induce
      growth arrest and apoptosis. Since the identification of a well-characterized
      functional polymorphism, G870A in exon 4 of CCND1, several molecular
      epidemiological studies were conducted in recent years to evaluate the
      association between G870A and breast cancer risk in diverse populations. However,
      the results remain conflicting rather than conclusive. This meta-analysis on
      5,371 cases with breast cancer and 5,336 controls from 7 published case-control
      studies showed that the variant allele 870A was associated with a significantly
      increased risk of breast cancer (AA vs. GG: OR = 1.18, 95% CI = 1.06-1.32; AG vs.
      GG: OR = 1.12, 95% CI = 1.01-1.23; AA/AG vs. GG: OR = 1.14, 95% CI = 1.04-1.25)
      without any between-study heterogeneity. In the stratified analysis by race, we
      found that the increased breast cancer risk associated with G870A polymorphism
      was more evident in Caucasians (OR = 1.14, 95% CI = 1.01-1.28, P = 0.88 for
      heterogeneity test), but not significant in Asians (OR = 1.10, 95% CI = 0.85
      1.42, P = 0.05 for heterogeneity test). The results suggest that CCND1 G870A
      polymorphism may contribute to breast cancer development, especially in
      Caucasians. Additional well-designed large studies were required for the
      validation of this association in different populations.

PMID- 18819001
TI  - BRCA1/BRCA2 mutation status and clinical-pathologic features of 108 male breast
      cancer cases from Tuscany: a population-based study in central Italy.
AB  - BACKGROUND: Male breast cancer (MBC) is a rare and scarcely investigated disease.
      The strongest genetic risk factor for MBC is represented by inherited BRCA2
      mutations, whereas the association between MBC and BRCA1 mutations is less clear.
      MBC appears to be biologically similar to breast cancer in females, however the
      phenotypic characteristics of BRCA1/2-related MBCs are not yet well elucidated.
      OBJECTIVE: To investigate the genetic and phenotypic characteristics of MBC in a
      large and well-characterized population-based series of 108 MBCs from Tuscany
      (Central Italy) and to evaluate associations between BRCA1/BRCA2 mutation status
      and clinical-pathological features including breast/ovarian cancer first-degree
      family history, tumor histology and grade, proliferative activity,
      estrogen/progesterone receptors (ER/PR) and epidermal growth factor receptor 2
      (HER2) expression. Results BRCA1/BRCA2 mutations were identified in ten MBCs, in
      particular, two cases (1.9%) carried BRCA1 and eight cases (7.4%) carried BRCA2
      mutations. The same BRCA1 mutation (3347delAG) was detected in two unrelated MBC
      cases. Three novel BRCA2 pathogenic mutations were found. Statistically
      significant associations emerged between BRCA2-related tumors and absence of PR
      expression (P = 0.008), HER2 over-expression (P = 0.002) and high tumor grade (P
      = 0.005). Conclusions Here, we (i) reported that in our population about 9% of
      MBC cases are accounted for by BRCA1/BRCA2 mutations; (ii) enlarged the BRCA2
      mutational spectrum and (iii) characterized a specific phenotype associated with
      BRCA2-related MBCs suggestive of aggressive behavior. Overall, our results may
      have important implications on clinical management for this rare disease.

PMID- 18819002
TI  - Validation of 70-gene prognosis signature in node-negative breast cancer.
AB  - PURPOSE: The 70-gene prognosis signature (van't Veer et al., Nature 415(6871):530
      536, 2002) may improve the selection of lymph node-negative breast cancer
      patients for adjuvant systemic therapy. Optimal validation of prognostic
      classifiers is of great importance and we therefore wished to evaluate the
      prognostic value of the 70-gene prognosis signature in a series of relatively
      recently diagnosed lymph node negative breast cancer patients. METHODS: We
      evaluated the 70-gene prognosis signature in an independent representative series
      of patients with invasive breast cancer (N = 123; <55 years; pT1-2N0; diagnosed
      between 1996 and 1999; median follow-up 5.8 years) by classifying these patients
      as having a good or poor prognosis signature. In addition, we updated the follow
      up of the node-negative patients of the previously published validation-series
      (Van de Vijver et al., N Engl J Med 347(25):1999-2009, 2002; N = 151; median
      follow-up 10.2 years). The prognostic value of the 70-gene prognosis signature
      was compared with that of four commonly used clinicopathological risk indexes.
      The endpoints were distant metastasis (as first event) free percentage (DMFP) and
      overall survival (OS). RESULTS: The 5-year OS was 82 +/- 5% in poor (48%) and 97
      +/- 2% in good prognosis signature (52%) patients (HR 3.4; 95% CI 1.2-9.6; P =
      0.021). The 5-years DMFP was 78 +/- 6% in poor and 98 +/- 2% in good prognosis
      signature patients (HR 5.7; 95% CI 1.6-20; P = 0.007). In the updated series (N =
      151; 60% poor vs. 40% good), the 10-year OS was 51 +/- 5% and 94 +/- 3% (HR 10.7;
      95% CI 3.9-30; P < 0.01), respectively. The DMFP was 50 +/- 6% in poor and 86 +/-
      5% in good prognosis signature patients (HR 5.5; 95% CI 2.5-12; P < 0.01). In
      multivariate analysis, the prognosis signature was a strong independent
      prognostic factor in both series, outperforming the clinicopathological risk
      indexes. CONCLUSION: The 70-gene prognosis signature is also an independent
      prognostic factor in node-negative breast cancer patients for women diagnosed in
      recent years.

PMID- 18819003
TI  - Lysis of cancer cells by autologous T cells in breast cancer pleural effusates
      treated with anti-EpCAM BiTE antibody MT110.
AB  - In the present study, the efficacy of a new drug, i.e. the bispecific single
      chain antibody MT110 targeting the epithelial antigen EpCAM and the T-cell
      antigen CD3 was tested ex vivo in malignant pleural effusions (MPEs). EpCAM+
      epithelial cells were found in 78% of the MPEs (n = 18). Ex vivo treatment of
      seven MPEs resulted in a dose-dependent specific lysis of 37 +/- 27% (+/- SD)
      EpCAM+ cells with 10 ng/ml (P = 0.03) and 57 +/- 29.5% EpCAM+ cells with 1,000
      ng/ml MT110 (P = 0.016) after 72 h. As a prerequisite for redirected lysis,
      stimulation of the autologous CD4+ and CD8+ cells in MPE by 1,000 ng/ml MT110
      resulted in 21 +/- 17% CD4+/CD25+ and 29.4 +/- 22% CD8+/CD25+ cells (P = 0.016,
      respectively) after 72 h. This was confirmed by a 22-fold release of TNF-alpha
      and 230-fold release of IFN-gamma (1,000 ng/ml, 48 h, P = 0.03, respectively).
      Thus, relapsed breast cancer patients resistant to standard treatment might
      benefit from targeted therapy using MT110.

PMID- 18819004
TI  - Apoptotic resistance exhibited by dexamethasone-resistant murine 7TD1 cells is
      controlled independently of interleukin-6 triggered signaling.
AB  - Interleukin-6 (IL6)-mediated signaling is known to play a role in pathogenesis
      and resistance in several cancers like multiple myeloma (MM). In this report we
      used the IL6-dependent 7TD1 murine B-cell hybridoma as an in vitro model to study
      the interactions between IL6-signaling pathways and the development of
      dexamethasone resistance. Though in initial stages, 7TD1 cells grew IL6-dependent
      and were sensitive to dexamethasone-induced apoptosis, chronic exposure to
      dexamethasone led to a dexamethasone-resistant phenotype (7TD1-Dxm) that grew
      independent of exogenous IL6. While IL6-mediated JAK/STAT3 and PI3K/AKT signaling
      was important for proliferation of both cell lines, as shown in proliferation
      assays using the respective pathway inhibitors, AG490 and LY294002, the resistant
      cells were insensitive to induction of apoptosis using the same. STAT3 was
      constitutively phosphorylated in resistant cells and inhibition of its
      dimerization induced apoptosis but did not alter their insensitivity to
      dexamethasone. Our results suggest a role of entities downstream of IL6-mediated
      JAK/STAT3 signaling in development of dexamethasone resistance by 7TD1-Dxm cells.

PMID- 18819005
TI  - Specific protein nitration in nitric oxide-induced apoptosis of human monocytes.
AB  - The sustained overproduction of nitric oxide (NO) observed in inflammatory
      conditions can contribute to cell demise by affecting apoptosis. Nitration of
      tyrosine residues occurs in a range of diseases involving macrophage activation.
      Since NO induces apoptosis in monocytes/macrophages, we tested the hypothesis
      that nitration of specific proteins could result in apoptotic cell death. The
      peroxynitrite generator SIN-1 promoted apoptosis in monocytes based on
      oligonucleosomal DNA fragmentation, caspase-3 and -9 activation, Bcl-2 depletion
      and accumulation of Bax and p53 proteins. We also found that the signaling
      pathway triggered by SIN-1 was initiated through tyrosine kinase and Rac
      activation and resulted in increased JNK and p38 activities. Among the tyrosine
      nitrated proteins, Rac and Lyn were identified. Using specific inhibitors for
      different signaling and effector molecules involved in the apoptotic process we
      demonstrate that NO, via protein-nitration, could play an important role in
      controlling the inflammatory response by regulation of monocyte homeostasis.

PMID- 18819006
TI  - Nanogram per milliliter-level immunologic detection of alpha-fetoprotein with
      integrated rotating-resonance microcantilevers for early-stage diagnosis of
      heptocellular carcinoma.
AB  - Nanogram per milliliter-level ultra-low concentration detection of alpha
      fetoprotein (AFP), which is an important marker for heptocellular carcinoma, is
      in favor of early-stage prognosis and disease diagnosis. On-the-spot rapid
      detection of such antigens as AFP highly requires innovative micro/nano
      techniques. To meet this requirement, an advanced resonant microcantilever is
      developed and used for screening the tumor marker at nanogram per milliliter
      level. The sensing principle of the resonant microcantilever is measuring
      frequency-shift versus specific-adsorbed mass. With both electromagnetic
      resonance-exciting and piezoresistive readout elements on-chip integrated, the
      microcantilever sensor is operated in a rotating resonance mode to improve
      sensitivity and resolution to specific mass adsorption. Prior to detection of AFP
      with previously immobilized anti-AFP antibody, the antigen-antibody specific
      binding is confirmed with an enzyme linked immunosorbent assay experiment. By
      implementing the specific reaction in liquid and reading out the sensor signal in
      lab air environment, the micromechanical sensor has achieved the sensitive scale
      between 2 and 20 ng/ml. To effectively depress cross-talk signal and improve
      resolution, the insensitive regions of the cantilever surface are pre-modified
      with 2-[methoxy (polyethyleneoxy) propyl] trimethoxysilane for nonspecific bio
      adsorption minimization. Finally, a better AFP detecting limit than 2 ng/mL is
      experimentally achieved. The label-free resonant microcantilever sensor is
      promising in low-cost or even disposable early-stage prognosis and diagnosis of
      tumors.

PMID- 18819007
TI  - An investigation of the effects of inlet channel geometry on electrokinetic
      instabilities.
AB  - Numerical and experimental investigations are performed to examine the
      feasibility of inducing electrokinetic instability (EKI) phenomena in two-channel
      junctions containing two aqueous electrolytes with a 10:1 conductivity ratio via
      the application of a low-intensity DC electrical field. A deep microchannel with
      700 microm in depth and 100 microm in width was designed, fabricated and used in
      this investigation. The results show that when the species streams are injected
      such that the conductivity gradient between them is perpendicular to the DC
      electrical driving field, an EKI effect can only be induced by applying a high
      electrical field intensity of 0.54 V/cm. However, when the potentials applied to
      the reservoirs of the microchip are switched such that the conductivity gradient
      is not perpendicular to the electrical field, flow instability can be achieved by
      applying a lower electrical field intensity.

PMID- 18819008
TI  - Methodological challenges in causal research on racial and ethnic patterns of
      cognitive trajectories: measurement, selection, and bias.
AB  - Research focused on understanding how and why cognitive trajectories differ
      across racial and ethnic groups can be compromised by several possible
      methodological challenges. These difficulties are especially relevant in research
      on racial and ethnic disparities and neuropsychological outcomes because of the
      particular influence of selection and measurement in these contexts. In this
      article, we review the counterfactual framework for thinking about causal effects
      versus statistical associations. We emphasize that causal inferences are key to
      predicting the likely consequences of possible interventions, for example in
      clinical settings. We summarize a number of common biases that can obscure causal
      relationships, including confounding, measurement ceilings/floors, baseline
      adjustment bias, practice or retest effects, differential measurement error,
      conditioning on common effects in direct and indirect effects decompositions, and
      differential survival. For each, we describe how to recognize when such biases
      may be relevant and some possible analytic or design approaches to remediating
      these biases.

PMID- 18819009
TI  - Detection of protein-ligand interactions by NMR using reductive methylation of
      lysine residues.
AB  - We show that reductive methylation of proteins can be used for highly sensitive
      NMR identification of conformational changes induced by metal- and small molecule
      binding, as well as protein-protein interactions. Reductive methylation of
      proteins introduces two (13)C-methyl groups on each lysine in the protein of
      interest. This method works well even when the lysines are not actively involved
      in the interaction, due to changes in the microenvironments of lysine residues.
      Most lysine residues are located on the protein exterior, and the exposed (13)C
      methyl groups may exhibit rapid localized motions. These motions could be faster
      than the tumbling rate of the molecule as a whole. Thus, this technique has great
      potential in the study of large molecular weight systems which are currently
      beyond the scope of conventional NMR methods.

PMID- 18819010
TI  - Transcriptome analysis approaches for the isolation of trichome-specific genes
      from the medicinal plant Cistus creticus subsp. creticus.
AB  - Cistus creticus subsp. creticus is a plant of intrinsic scientific interest due
      to the distinctive pharmaceutical properties of its resin. Labdane-type
      diterpenes, the main constituents of the resin, exhibit considerable
      antibacterial and cytotoxic activities. In this study chemical analysis of
      isolated trichomes from different developmental stages revealed that young leaves
      of 1-2 cm length displayed the highest content of labdane-type diterpenes (80
      mg/g fresh weight) whereas trichomes from older leaves (2-3 or 3-4 cm) exhibited
      gradual decreased concentrations. A cDNA library was constructed enriched in
      transcripts from trichomes isolated from young leaves, which are characterized by
      high levels of labdane-type diterpenes. Functional annotation of 2,022 expressed
      sequence tags (ESTs) from the trichome cDNA library based on homology to A.
      thaliana genes suggested that 8% of the putative identified sequences were
      secondary metabolism-related and involved primarily in flavonoid and terpenoid
      biosynthesis. A significant proportion of the ESTs (38%) displayed no significant
      similarity to any other DNA deposited in databases, indicating a yet unknown
      function. Custom DNA microarrays constructed with 1,248 individual clones from
      the cDNA library facilitated transcriptome comparisons between trichomes and
      trichome-free tissues. In addition, gene expression studies in various Cistus
      tissues and organs for one of the genes highlighted as the most differentially
      expressed by the microarray experiments revealed a putative sesquiterpene
      synthase with a trichome-specific expression pattern. Full length cDNA isolation
      and heterologous expression in E. coli followed by biochemical analysis, led to
      the characterization of the produced protein as germacrene B synthase.

PMID- 18819011
TI  - Family history and age at onset of breast cancer in Hispanic and non-Hispanic
      white women.
AB  - OBJECTIVES: To evaluate the association between family history of breast cancer
      and breast cancer risk among Hispanic and non-Hispanic white (NHW) women.
      METHODS: Logistic regression models were used to compute unadjusted and adjusted
      odds ratios (ORs) and 95% confidence intervals (CIs) using data collected from
      the 4-Corners Breast Cancer Study, a population-based case-control study of
      breast cancer conducted in the Southwest United States (3,074 NHW and 1,647
      Hispanic women). RESULTS: The association between family history of breast cancer
      and early-onset breast cancer risk differs among NHW and Hispanic women. Among
      women <50 years old, having a family history of breast cancer was associated with
      a greater increase in risk among NHWs, with an OR of 2.34 (95% CI: 1.64-3.35)
      when compared to an OR of 1.32 (95% CI: 0.82-2.19) for Hispanics. This difference
      in risk was not observed among women 50 years and older, with an OR of 1.69 (95%
      CI: 1.34-2.13) for NHW and 1.47 (95% CI: 1.03-2.10) for Hispanics. CONCLUSIONS:
      Family history of breast cancer poses a greater risk for early-onset breast
      cancers among NHW when compared to Hispanic women and may reflect ethnic
      differences in certain predisposing genetic factors that promote breast cancer
      development.

PMID- 18819012
TI  - Impacts of water resources development on flow regimes in the Brazos River.
AB  - The Brazos River, the second largest basin in Texas, represents one of the most
      highly developed river systems in the state. Thirty-nine reservoirs with
      capacities greater than 5,000 acre-feet are currently in operation in the basin.
      Impacts on stream ecosystems are evidenced by changes in flow regimes and
      resulting changes in fish assemblages over the past 50 years. These changes have
      been widely attributed to human impacts, through the construction of dams,
      diversion of water supplies for agricultural and municipal uses, and land use
      change. However, streamflow regimes result from a complex mix of drivers that
      include climate, topography, land cover, land use practices, reservoir management
      practices, dam releases, and water consumption patterns, making determination of
      anthropogenic impacts problematic. This study quantifies changes in flow regime
      and probable historical drivers including precipitation, dam construction,
      population growth, and changing water demand in the Brazos River basin over the
      past 100 years. Results indicate that the climate of the basin has been
      relatively stable over the study period, while large-scale changes in human
      population densities and intense water resources development are correlated with
      impacts on flow regimes, decreasing the frequency and magnitude of high flow
      events and stabilizing low flows. These changes have resulted in an increase of
      habitat generalist fish species, a decrease of native obligate riverine fishes,
      and an overall homogenization of species assemblages. The results of this study
      indicate the importance of combining ecological data with an assessment of social
      drivers for a greater understanding of the dynamics of river basin systems.

PMID- 18819013
TI  - Forecasts using Box-Jenkins models for the ambient air quality data of Delhi
      City.
AB  - The monthly maximum of the 24-h average time-series data of ambient air quality
      sulphur dioxide (SO(2)), nitrogen dioxide (NO(2)) and suspended particulate
      matter (SPM) concentration monitored at the six National Ambient Air Quality
      Monitoring (NAAQM) stations in Delhi, was analysed using Box-Jenkins modelling
      approach (Box et al. 1994). Univariate linear stochastic models were developed to
      examine the degree of prediction possible for situations where only the past
      record of pollutant data are available. In all, 18 models were developed, three
      for each station for each of the respective pollutant. The model evaluation
      statistics suggest that considerably satisfactory real-time forecasts of
      pollution concentrations can be generated using the Box-Jenkins approach. The
      developed models can be used to provide short-term, real-time forecasts of
      extreme air pollution concentrations for the Air Quality Control Region (AQCR) of
      Delhi City, India.

PMID- 18819014
TI  - Mycoplasma contamination of murine embryonic stem cells affects cell parameters,
      germline transmission and chimeric progeny.
AB  - Murine embryonic stem cells (mESCs) inoculated at passage P13 with the mycoplasma
      species M. hominis, M. fermentans and M. orale and cultured over 20 passages
      showed reduced growth rate and viability (P < 0.0001) compared to control mESCs.
      Spectral karyotypic analysis of mycoplasma-infected mESCs showed a number of non
      clonal chromosomal aberrations which increased with the duration of infection.
      The differentiation status of the infected mESCs was most affected at passage
      P13+6 where the infection was strongest and 46.3% of the mESCs expressed both
      POU5F1 and SSEA-1 markers whereas 84.8% of control mESCs expressed both markers.
      The percentage of germline chimeras from mycoplasma-infected mESCs was examined
      after blastocyst injection and embryo transfer to suitable recipients at
      different passages and, compared to the respective control group, was most
      affected at passage P13+5 (50% vs. 90%; P < 0.07). Further reductions were
      obtained at the same passage in the percentage of litters born (50% vs. 100%; P <
      0.07) and in the percentage of pups born (22% vs. 45%; P < 0.001). Thirty three
      chimeras (39.8%) obtained from blastocyst injection with mycoplasma-infected
      mESCs showed reduced body weight (P < 0.0001), nasal discharge,
      osteoarthropathia, and cachexia. Flow cytometric analysis of plasma from chimeras
      produced with mycoplasma-infected mESCs revealed statistically significant
      differences in the proportions of T-cells and increased levels of IgG1 (P <
      0.001), IgG2a (P < 0.05) and IgM (P < 0.05), anti-DNA antibodies (P < 0.05) and
      rheumatoid factor (P < 0.01). The present data indicate that mycoplasma
      contamination of mESCs affects various cell parameters, germline transmission,
      and postnatal development of the resulting chimeras.

PMID- 18819015
TI  - Effects of methanol on the Si-state transitions in photosynthetic water
      splitting.
AB  - From a chemical point of view methanol is one of the closest analogues of water.
      Consistent with this idea EPR spectroscopy studies have shown that methanol binds
      at-or at least very close to-the Mn(4)O(x)Ca cluster of photosystem II (PSII). In
      contrast, Clark-type oxygen rate measurements demonstrate that the O(2) evolving
      activity of PSII is surprisingly unaffected by methanol concentrations of up to
      10%. Here we study for the first time in detail the effect of methanol on
      photosynthetic water-splitting by employing a Joliot-type bare platinum
      electrode. We demonstrate a linear dependence of the miss parameter for S( i )
      state advancement on the methanol concentrations in the range of 0-10% (v/v).
      This finding is consistent with the idea that methanol binds in PSII with similar
      affinity as water to one or both substrate binding sites at the Mn(4)O(x)Ca
      cluster. The possibility is discussed that the two substrate water molecules bind
      at different stages of the cycle, one during the S(4) --> S(0) and the other
      during the S(2) --> S(3) transition.

PMID- 18819016
TI  - EPR, ENDOR, and special TRIPLE measurements of P(*+) in wild type and modified
      reaction centers from Rb. sphaeroides.
AB  - The influence of the protein environment on the primary electron donor, P, a
      bacteriochlorophyll a dimer, of reaction centers from Rhodobacter sphaeroides,
      has been investigated using electron paramagnetic resonance and electron nuclear
      double resonance spectroscopy. These techniques were used to probe the effects on
      P that are due to alteration of three amino acid residues, His L168, Asn L170,
      and Asn M199. The introduction of Glu at L168, Asp at L170, or Asp at M199
      changes the oxidation/reduction midpoint potential of P in a pH-dependent manner
      (Williams et al. (2001) Biochemistry 40, 15403-15407). For the double mutant His
      L168 to Glu and Asn at L170 to Asp, excitation results in electron transfer along
      the A-side branch of cofactors at pH 7.2, but at pH 9.5, a long-lived state
      involving B-side cofactors is produced (Haffa et al. (2004) J Phys Chem B 108, 4
      7). Using electron paramagnetic resonance spectroscopy, the mutants with
      alterations of each of the three individual residues and a double mutant, with
      changes at L168 and L170, were found to have increased linewidths of 10.1-11.0 G
      compared to the linewidth of 9.6 G for wild type. The Special TRIPLE spectra were
      pH dependent, and at pH 8, the introduction of aspartate at L170 increased the
      spin density ratio, rho (L)/rho (M), to 6.1 while an aspartate at the symmetry
      related position, M199, decreased the ratio to 0.7 compared to the value of 2.1
      for wild type. These results indicate that the energy of the two halves of P
      changes by about 100 meV due to the mutations and are consistent with the
      interpretation that electrostatic interactions involving these amino acid
      residues contribute to the switch in pathway of electron transfer.

PMID- 18819017
TI  - Relationship between susceptibility of Candida spp. isolates to amphotericin B
      and death or survival of patients with candidemia episodes.
AB  - In this study, the susceptibility to amphotericin B of Candida spp. isolates
      obtained from patients with candidemia was related to their respective clinical
      outcomes. The susceptibility tests were carried out in three culture media: RPMI
      1640, Antibiotic medium 3 and Yeast Nitrogen Base dextrose. We have found that
      minimal inhibitory concentrations and minimal fungicidal concentrations obtained
      using AM3 and YNBd media were significantly higher for Candida spp. from patients
      who died than for those from patients who survived the candidemia (P < 0.05). The
      assays with RPMI 1640 medium did not show these differences.

PMID- 18819018
TI  - Cloning, expression and subcellular distribution of a Rana grylio virus late gene
      encoding ERV1 homologue.
AB  - An essential for respiration and viability (ERV1) homologue, 88R, was cloned and
      characterized from Rana grylio virus (RGV). Database searches found its
      homologues in all sequenced iridoviruses, and sequence alignment revealed a
      highly conserved motif shared by all ERV1 family proteins: Cys-X-X-Cys. RT-PCR
      and western blot analysis revealed that 88R begins to transcribe and translate at
      6 h postinfection (p.i.) and remains detectable at 48 h p.i. during RGV infection
      course. Furthermore, using drug inhibition analysis by a de novo protein
      synthesis inhibitor and a viral DNA replication inhibitor, RGV 88R was classified
      as a late (L) viral gene during the in vitro infection. 88R-EGFP fusion protein
      was observed in both the cytoplasm and nucleus of pEGFP-N3-88R transfected EPC
      cells. Although result of immunofluorescence is similar, 88R protein was not
      detected in viromatrix. Moreover, function of RGV 88R on virus replication were
      evaluated by RNAi assay. Nevertheless, effect of knockdown of RGV 88R expression
      on virus replication was not detected in cultured fish cell lines. Collectively,
      current data indicate that RGV 88R was a late gene of iridovirus encoding protein
      that distributed both the cytoplasm and nucleus.

PMID- 18819019
TI  - A cyclophilin A inducible expressed in gonad of zhikong scallop Chlamys farreri.
AB  - Cyclophilin A (CypA), a receptor for the immunosuppressive agent cyclosporin A
      (CsA), is a cis-trans peptidyl-prolyl isomerase (PPIase) which accelerates the
      cis-trans isomerization of prolyl-peptide bonds, interacts with a variety of
      proteins and therefore regulates their activities. One CypA (designated CfCypA)
      cDNA was cloned from Chlamys farreri by expressed sequence tag (EST) and rapid
      amplification of cDNA ends (RACE) techniques. The full-length cDNA of CfCypA
      consisted of 1,248 nucleotides with a canonical polyadenylation signal sequence
      AATAAA, a poly (A) tail, and an open reading frame (ORF) of 495 nucleotides
      encoding a polypeptide of 164 amino acids. The deduced amino acid sequence shared
      high similarity with CypA from the other species, indicating that CfCypA should
      be a new member of the CypA family. Quantitative real-time (RT) PCR was employed
      to assess the mRNA expression of CfCypA in various tissues and its temporal
      expression in haemocytes and gonad of scallops challenged with Vibrio
      anguillarum. The mRNA transcripts of CfCypA could be detected in all the examined
      tissues with highest expression level in gonad. After bacterial challenge, the
      expression level of CfCypA was almost unchanged in haemocytes, but up-regulated
      in gonad and increased to the peak (22.59-fold; P < 0.05) at 4 h post-injection,
      and then dropped to the original level at 8 h post-injection. These results
      indicated that CfCypA was constitutive expressed in haemocytes, but could be
      induced in gonad, and perhaps played a critical role in response to the bacterial
      challenge in gonad.

PMID- 18819020
TI  - ATP release from the human ureter on distension and P2X(3) receptor expression on
      suburothelial sensory nerves.
AB  - It is not clear how the increase in intraluminal pressure behind an obstructing
      ureteric calculus causes an increase in action potential frequency in ureteric
      sensory nerves so the pain messages are transmitted to the brain. It has been
      proposed that ureteric distension causes urothelial release of ATP, which
      activates purinoceptors on suburothelial nociceptive sensory nerves. The purpose
      of this study was to determine whether distension of the human ureter results in
      the release of ATP and whether the nociceptive P2 receptor, P2X(3), is expressed
      on suburothelial sensory nerves in the human ureter. Human ureter segments were
      perfused with Krebs solution and intermittently distended to a range of
      pressures. Samples of perfusate were collected throughout and the ATP
      concentration ([ATP]) was determined using a luciferin-luciferase assay. Sections
      of ureter were stained using antibodies against P2X(3) and capsaicin receptors
      (TRPV1). [ATP] rose to more than 10 times baseline levels after distension beyond
      a threshold of 25-30 cmH(2)O. Immunofluorescence studies on consecutive frozen
      sections showed that suburothelial nerves stained positively for P2X(3) and
      capsaicin receptors, with no staining in controls. These findings are consistent
      with the hypothesis that purinergic signalling is involved in human ureteric
      mechanosensory transduction, leading to nociception.

PMID- 18819021
TI  - Hsp72 chaperone function is dispensable for protection against stress-induced
      apoptosis.
AB  - In addition to its role as a molecular chaperone, heat shock protein 72 (Hsp72)
      protects cells against a wide range of apoptosis inducing stresses. However, it
      is unclear if these two roles are functionally related or whether Hsp72 inhibits
      apoptosis by a mechanism independent of chaperone activity. The N-terminal
      adenosine triphosphatase domain, substrate-binding domain and the C-terminal EEVD
      regulatory motif of Hsp72 are all essential for chaperone activity. In this
      study, we show that Hsp72 mutants with a functional substrate-binding domain but
      lacking chaperone activity retain their ability to protect cells against
      apoptosis induced by heat and tumor necrosis factor alpha. In contrast, a
      deletion mutant lacking a functional substrate-binding domain has no protective
      capacity. The ability of the Hsp72 substrate-binding domain to inhibit apoptosis
      independent of the regulatory effects of the adenosine triphosphate-binding
      domain indicates that the inhibition of apoptosis may involve a stable binding
      interaction with a regulatory substrate rather than Hsp72 chaperone activity.

PMID- 18819022
TI  - MASPIN's prognostic role in patients with advanced head and neck carcinoma
      treated with primary chemotherapy (carboplatin plus vinorelbine) and
      radiotherapy: preliminary evidence.
AB  - CONCLUSIONS: Our very preliminary results support the hypothesis that MASPIN
      expression in primary head and neck squamous cell carcinoma (HNSCC) may be a
      valuable parameter for predicting patients' responses to a treatment based on
      carboplatin plus vinorelbine combined with radiotherapy. OBJECTIVES: The roles of
      induction chemotherapy and combined chemoradiotherapy in the treatment of locally
      advanced unresectable HNSCCs have evolved rapidly. MASPIN has a unique tumour
      suppressing activity. Experimental evidence has shown that MASPIN suppresses
      tumour growth, angiogenesis, invasion and metastasis. We investigated the
      potential prognostic roles of MASPIN and p53 in a series of HNSCCs treated with
      carboplatin plus vinorelbine combined with radiotherapy. PATIENTS AND METHODS:
      Nineteen consecutive stage III or IV HNSCC patients were recruited. The treatment
      plan consisted of the administration of carboplatin on day 1 and vinorelbine on
      days 1 and 8. Four weeks later, carboplatin was administered concomitantly with
      radiation therapy. Expression of MASPIN and p53 was determined
      immunohistochemically in HNSCC diagnostic biopsies. RESULTS: A significant
      inverse relation was found between MASPIN expression and cN staging (p = 0.003).
      From a prognostic viewpoint, MASPIN expression was directly correlated with
      chemoradiotherapy response (p = 0.041). Moreover, the log-rank test showed a
      significant relationship between higher MASPIN expression and longer disease-free
      survival (p = 0.03), overall survival (p = 0.006) and disease-specific survival
      (p = 0.007).

PMID- 18819023
TI  - National surveillance of antifungal susceptibility of Candida species in South
      Korean hospitals.
AB  - We investigated the species distribution and antifungal susceptibility of Candida
      isolates from tertiary and non-tertiary hospitals in South Korea from 2002-2004.
      Of the 612 Candida isolates that were collected, Candida albicans, C.
      parapsilosis, C. tropicalis, and C. glabrata occurred most frequently, accounting
      for 97.3% and 96.8% of the isolates in tertiary and non-tertiary hospitals,
      respectively. C. albicans was the most common isolate, but the incidence of non
      C. albicansCandida species was higher than that of C. albicans in tertiary
      hospitals. The Candida species had much lower MIC(90) to voriconazole (tertiary
      hospitals: 0.5 microg/ml, non-tertiary hospitals: 0.25 microg/ml) than to
      fluconazole (tertiary hospitals: 8 microg/ml, non-tertiary hospitals: 4
      microg/ml). The MIC(90) of Candida isolates to 5-flucytosine in non-tertiary
      hospitals was two times higher than that observed in tertiary facilities. The C.
      glabrata isolates showed a tendency toward strong resistance to fluconazole, but
      C. parapsilosis isolates were susceptible to all of the evaluated antifungal
      agents. Voriconazole showed strong in vitro activity against Candida species,
      especially C. krusei, which is resistant to fluconazole and 5-flucytosine. To our
      knowledge, this is the first report of Candida antifungal susceptibility that
      includes non-tertiary hospitals in South Korea.

PMID- 18819024
TI  - When the half-full glass is appraised as half empty and memorised as completely
      empty: mood-congruent true and false recognition in depression is modulated by
      salience.
AB  - Since the 1980s a large body of empirical effort has been devoted to mood
      congruent memory (MCM) biases in clinical depression. Whereas there is broad,
      albeit not unequivocal, evidence that depressive patients retain negative
      valenced memory items better than neutral material, few studies have investigated
      false memories in depression. In a pilot study we gathered support for both
      enhanced true and false memory for emotional material in depression. The present
      study aimed to extend these preliminary findings. In view of investigations
      suggesting that arousing and meaningful stimuli have facilitated access to
      memory, personal salience was considered a moderator for MCM. In the present
      study 21 depressed and 22 healthy participants were presented six false memory
      lists dealing with neutral, negative, and positive themes. At recognition, each
      item had to be appraised for its degree of valence subsequent to an old-new
      judgement. Pre-categorised and subjective valence did not discriminate groups.
      However, relative to controls depressed patients showed both more veridical as
      well as false recognition for items that concurrently elicited higher salience
      ratings in patients. In contrast, group differences in recognition performance
      did not significantly affect salience ratings. Results indicate that salience
      modulates MCM and may account for discrepancies in the literature.

PMID- 18819025
TI  - Functional MRI of the primary somatosensory cortex in extinction to simultaneous
      bilateral tactile stimuli due to right temporal lobe stroke.
AB  - Patients with right posterior temporoparietal cortical lesions often exhibit
      extinction to tactile double simultaneous stimuli (EDSS). It is not known whether
      sensory unawareness-extinction results from suppression of sensory input into the
      somatosensory cortex (SI), inhibition of SI, or interference which prevents SI
      output from activating and being fully processed by association areas. A patient
      with EDSS due to a right temporal stroke sparing SI and posterior parietal cortex
      and eight age-matched healthy controls were studied with fMRI during tactile
      stimulation. The volume of activation of SI during tactile stimulation of the
      right hand, the left hand and both hands was measured and the patient's volume of
      activation was compared to that of the control subjects in each of these stimulus
      conditions. Although the patient demonstrated behavioral EDSS, during fMRI the
      patient's activation of SI on both sides was within the range of the control
      participants' volumes of activation. These findings suggest that EDSS in patients
      with a right temporal lobe stroke results from processing abnormalities that
      occur after these afferent tactile stimuli are processed by SI.

PMID- 18819026
TI  - Are preferences in emotional processing affected by distraction? Examining the
      age-related positivity effect in visual fixation within a dual-task paradigm.
AB  - Recent research has suggested that age-related positivity effects are eliminated
      under conditions of dual-task load (Knight et al., 2007, Emotion, 7, 705; Mather
      & Knight, 2005, Psychology and Aging, 20, 554), because the cognitive control
      resources necessary to enact such preferences are not available when individuals
      are distracted by competing information. We further examined how older adults'
      emotional information processing preferences are affected by distracting
      information by utilizing a within-subjects dual-task measure. Younger and older
      adults viewed a series of positive, negative, and neutral images both in
      conditions of full and divided attention. Fixation preferences to valenced images
      were assessed through eye tracking. Regardless of whether images were viewed in
      full or divided attention conditions, older adults demonstrated a preference in
      their fixation for positive and neutral in comparison to negative images. These
      results provide evidence that older adults' positive fixation preferences may not
      always necessitate full, cognitive control.

PMID- 18819027
TI  - Is it too soon for mesenchymal stem cell trials in people with ALS?
AB  - Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease
      affecting primarily the motor neurons. Stem cell therapy is under development as
      a possible treatment approach. A pilot study of intraspinal injections of
      mesenchymal stem cells (MSC) was conducted in 9 participants. We review this
      paper, the rationale, preclinical data and study design.

PMID- 18819028
TI  - Pneumococcal surface adhesin A (PsaA): a review.
AB  - Pneumococcal surface adhesin A (PsaA) is a surface-exposed common 37-kilodalton
      multi-functional lipoprotein detected on all known serotypes of Streptococcus
      pneumoniae. This lipoprotein belongs to the ABC-type transport protein complex
      that transports Mn(2+); it is also an adhesin that plays a major role in
      pneumococcal attachment to the host cell and virulence. PsaA is immunogenic and
      natural nasopharyngeal colonization of pneumococci elicits an increase in
      antibody towards PsaA. Hence, PsaA is being actively evaluated as a component of
      a vaccine in formulations composed of pneumococcal common proteins. PsaA has been
      expressed as an E. coli recombinant protein, purified, and evaluated in a phase
      one clinical trial. This article reviews PsaA, its structure and role in
      pneumococcal virulence, immunogenicity, and potential to reduce nasopharyngeal
      colonization (a major prerequisite for pneumococcal pathogenesis) as a component
      of a common pneumococcal protein vaccine.

PMID- 18819029
TI  - Glutaraldehyde cross-linked chitosan microspheres for controlled delivery of
      zidovudine.
AB  - Zidovudine-Chitosan microspheres were prepared by a suspension cross-linking
      method. The chitosan was dissolved in 2% acetic acid solution and this solution
      was dispersed in the light liquid paraffin. Span-80 was used as an emulsifier and
      glutaraldehyde as cross-linking agent. The prepared microspheres were slight
      yellow, free flowing and characterized by drug loading, infrared spectroscopy
      (IR), differential scanning colorimetry (DSC) and scanning electron microscopy
      (SEM). The in-vitro release studies are performed in pH 7.4 buffer solution.
      Microspheres produced are spherical and have smooth surfaces, with sizes ranging
      between 60-210 um, as evidenced by SEM and particle size analysis. The drug
      loaded microspheres showed up to 60% of entrapment and release was extended up to
      18-24 h. Among all the systems studied, the 35% Glutaraldehyde crosslinked,
      microspheres with 1 : 6 drug/chitosan ratio showed 75% release at 12 h. The
      infrared spectra and DSC thermograms showed stable character of zidovudine in the
      drug loaded microspheres and revealed the absence of drug-polymer interactions.
      Data obtained from in vitro release were fitted to various kinetic models and
      high correlation was obtained in the Higuchi model. The drug release was found to
      be diffusion controlled.

PMID- 18819030
TI  - Implicit overcompensation: the influence of negative self-instructions on
      performance of a self-paced motor task.
AB  - According to Wegner's (1994) theory of ironic processes of mental control, self
      instructions not to perform in a certain way, together with mental loads, can
      induce thoughts, emotions, and behaviours that are precisely the opposite of
      intention. Wegner's theory was tested against the implicit overcompensation
      hypothesis, which states that movement direction and magnitude are implicitly
      dictated by self-instruction, irrespective of load, promoting overcompensation of
      action. Two experiments were conducted using a golf-putting task. In Experiment
      1, 48 participants were randomly assigned to one of four load conditions:
      cognitive, visual, auditory, and self-presentation/incentive. In the experimental
      trials, participants were instructed to make the putt, but it was emphasized that
      the putt should not be left short of the target. Following the instructional
      strategy, putts landed significantly longer than at baseline, irrespective of
      load. In Experiment 2, 36 participants were divided into one of three groups,
      without load, in which different instructional sets (control, not putting long,
      and not putting short) were emphasized. A significant interaction emerged, as
      participants putted significantly longer or shorter than controls depending on
      the instructional set given. Overall, our findings support the implicit
      overcompensation hypothesis. Theoretical and practical considerations are
      discussed.

PMID- 18819031
TI  - Effect of PEG6000 on the in vitro and in vivo transdermal permeation of
      ondansetron hydrochloride from EVA1802 membranes.
AB  - The objective was to evaluate ethylene vinyl acetate (EVA) copolymer membranes
      with vinyl acetate content of 18% w/w (EVA1802) for transdermal delivery of
      ondansetron hydrochloride. The EVA1802 membranes containing selected
      concentrations (0, 5, 10 and 15% w/w) of PEG6000 were prepared, and subjected to
      in vitro permeation studies from a nerodilol-based drug reservoir. Flux of
      ondansetron from EVA1802 membranes without PEG6000 was 64.1 +/- 0.6
      microg/cm(2.)h, and with 10%w/w of PEG6000 (EVA1802-PEG6000-10) it increased to
      194.9 +/- 4.6 microg/cm(2.)h. However, with 15%w/w of PEG6000, EVA1802 membranes
      produced a burst release of drug which in turn decreased drug flux. The EVA1802
      PEG6000-10 membrane was coated with an adhesive emulsion, applied to rat
      epidermis and subjected to in vitro permeation studies against controls. Flux of
      ondansetron from transdermal patch across rat epidermis was 111.7 +/- 1.3
      microg/cm(2.)h, which is about 1.3 times the required flux. A TTS was fabricated
      using adhesive-coated EVA1802-PEG6000-10 membrane and other TTS components, and
      subjected to in vivo delivery in human volunteers against a control. It was
      concluded from the comparative pharmacokinetic study that TTS of ondansetron,
      prepared with EVA1802-PEG6000-10 membrane, provided average steady-state plasma
      concentration on par with multiple-dosed oral tablets, but with a low percent of
      peak-to-trough fluctuation.

PMID- 18819032
TI  - Stroke morbidity in Swedish- and Finnish-speaking populations of Turku, Finland.
AB  - OBJECTIVES: To examine differences in the morbidity and mortality of stroke
      between the Finnish- and Swedish-speaking populations in Turku, taking into
      account the socioeconomic differences between these groups. DESIGN: The
      population-based FINMONICA and FINSTROKE stroke registers recorded 5,135 stroke
      events among persons aged 25-99 years in Turku during 1988-1998. Events in
      persons aged > or =75 years were not registered in 1993-1995. Information on
      these persons' native language and socioeconomic status (SES) (measured by
      taxable income, profession and years of education) were obtained by record
      linkage with the files of Statistics Finland. RESULTS: Swedish-speaking men had a
      lower attack rate of ischaemic stroke than Finnish-speaking men (270, 95%
      Confidence Interval (CI) 214-326 versus 370, 95% CI 352-389, per 100,000
      inhabitants per year) and the difference remained significant after adjustment
      for SES. Among women, the attack rates of ischaemic stroke were similar in both
      language groups. CONCLUSIONS: The attack rate of ischaemic stroke was lower among
      Swedish-speaking than among Finnish-speaking men. This difference was not totally
      explained by the higher SES of the Swedish-speaking population.

PMID- 18819033
TI  - HRQoL after coronary artery bypass grafting and percutaneous coronary
      intervention for stable angina.
AB  - OBJECTIVES: To assess the health related quality of life (HRQoL) and the change
      in the NYHA class after coronary artery bypass grafting (CABG) or percutaneous
      coronary intervention (PCI) in the management of stable coronary artery disease
      (CAD). The study was non-randomized. CABG group consisted of 240 patients and 229
      patients were treated with PCI. HRQoL was measured prospectively by the 15D
      instrument. RESULTS: Three-year survival was 95.0 and 95.6% (NS). The HRQoL
      improved statistically in both groups until 6 months after treatment but
      deteriorated towards the end of the follow-up of 36 months. Clinically evident
      improvement of the HRQoL and decrease of the NYHA class took place more
      frequently among CABG patients. CONCLUSIONS: Despite initially more serious
      preoperative state and more demanding procedure CABG patients achieve equal level
      of HRQoL when compared with PCI patients. CABG patients may also obtain better
      relief from symptoms in mid-term follow-up. HRQoL cannot be the only factor to
      determine outcome after invasive treatment of CAD but it has to be placed in the
      context of the overall situation.

PMID- 18819034
TI  - Cyclooxygenase-2, multidrug resistance 1, and breast cancer resistance protein
      gene polymorphisms and inflammatory bowel disease in the Danish population.
AB  - OBJECTIVE: Crohn's disease (CD) and ulcerative colitis (UC) are characterized by
      an impaired mucosal defence to normal constituents of the intestinal flora and a
      dysregulated inflammatory response. The purpose of the study was to investigate
      whether single nucleotide polymorphisms (SNPs) in genes involved in these
      processes were associated with CD and UC. MATERIAL AND METHODS: Allele
      frequencies of the cyclooxygenase 2 (COX-2/PTGS2/PGHS2) G-765C and breast cancer
      resistance protein (BCRP/ABCG2) C421A as well as allele and haplotype frequencies
      of multidrug resistance 1 (MDR1, ABCB1) SNPs G2677T/A, C3435T and G-rs3789243-A
      (intron 3) were assessed in a Danish case-control study comprising 373 CD and 541
      UC patients and 796 healthy controls. RESULTS: Carriers of the homozygous COX-2
      and MDR1 intron 3 variant had a relatively high risk of CD, odds ratio (95% CI)
      (OR (95% CI))=2.86 ((1.34-5.88) p=0.006) and 1.39 ((0.99-1.92) p=0.054),
      respectively, and for UC of 2.63 ((1.33-5.26) p=0.005) and 1.28 ((0.96-1.51)
      p=0.093), respectively, assuming complete dominance. No association was found for
      BCRP or other MDR1 SNPs, or for selected MDR1 haplotypes. No effect-modification
      of smoking habit at the time of diagnosis was found. CONCLUSIONS: An effect of
      the COX-2 polymorphism on both CD and UC was shown which is compatible with the
      presence of a recessive allele in linkage equilibrium with the SNP marker in the
      COX-2 gene. The polymorphism located in intron 3 of the MDR1 gene showed a weak
      association with CD, and a marginally suggestive association with UC.

PMID- 18819035
TI  - Gliadin IgG antibodies and circulating immune complexes.
AB  - OBJECTIVE: Circulating immune complexes (CICs) in blood are associated with
      autoimmune-diseases such as systemic lupus erythematosus, immune complex
      glomerulonephritis, rheumatoid arthritis and vasculitis. However, slightly
      increased serum concentrations of such CICs are sometimes also found in healthy
      individuals. The objective of the current study was to assess whether food
      antigens could play a role in the formation of CICs. MATERIAL AND METHODS: A
      total of 352 (265 F, 87 M), so far, healthy individuals were tested for CICs
      containing C1q and immunoglobulin G (IgG) as well as for gliadin IgG antibodies
      using the ELISA technique. Additionally, fructose and lactose malabsorption was
      assessed using hydrogen breath tests. RESULTS: In our study, 15.3% (54/352) of
      the patients presented with elevated CIC concentrations (above 50 microg/ml) and
      6.5% (23/352) of the study population were positive for gliadin IgG antibodies
      (above 20 U/ml). CIC concentration levels were significantly higher in the group
      with elevated gliadin IgG antibodies (CIC median: 49.0 microg/ml) compared with
      the group with normal levels of gliadin IgG antibodies (CIC median: 30.0
      microg/ml; Mann-Whitney U-test, U=1992; p <0.001). As expected, there was no
      difference in CIC concentrations (Mann-Whitney U-test, U=6106; p=0.783) and
      gliadin IgG (Mann-Whitney U-test, U=3761; p=0.411) between patients in the
      fructose or lactose malabsorber groups and the subjects without malabsorption.
      CONCLUSIONS: The results of this study indicate that certain food antigens (e.g.
      gluten) could play a role in the formation of CICs. An association between CICs
      and fructose or lactose malabsorption seems to be improbable.

PMID- 18819037
TI  - Utility of quantitative 99mTc-phytate scintigraphy to diagnose early-stage non
      alcoholic steatohepatitis.
AB  - OBJECTIVE: In patients with non-alcoholic fatty liver disease (NAFLD), liver
      biopsy remains the only reliable method to differentiate simple steatosis from
      non-alcoholic steatohepatitis (NASH). The objective of this study was to evaluate
      the efficacy of non-invasive (99m)Tc-phytate scintigraphy in the diagnosis of
      NASH. MATERIAL AND METHODS: Thirty-seven patients with suspected NAFLD at the
      time of liver biopsy also underwent (99m)Tc-phytate scintigraphy. Signal
      intensities of regions of interest (ROI) in the liver, spleen, and heart were
      measured. We also examined scintigraphic features in a nutritional model of NASH
      in rats fed a methionine- and choline-deficient (MCD) diet. RESULTS: The
      liver/spleen uptake ratio determined by scintigraphy was significantly decreased
      in patients with NASH in comparison with patients with simple steatosis. The
      liver/spleen ratio was an independent predictor distinguishing NASH from simple
      steatosis. The decrease was observed for all stages of NASH, including the early
      stage (stages 1 and 0). In animal studies, the liver/spleen uptake ratio was
      significantly decreased in rats after 8 weeks of MCD dietary feeding in
      comparison with control diet-fed rats. CONCLUSIONS: The non-invasive (99m)Tc
      phytate scintigraphy test is a reliable tool to differentiate NASH from simple
      steatosis.

PMID- 18819038
TI  - GORD patients on chronic acid suppressive medication: a population-average
      psychological state.

PMID- 18819039
TI  - Hyperamylasaemia and/or hyperlipasaemia: incidence and underlying causes in
      hospitalized patients with non-pancreatic diseases.
AB  - OBJECTIVE: There are no recommendations on how to proceed in patients with
      increased pancreatic enzyme activities but non-pancreatic diseases. The objective
      of this study was to investigate prospectively in a general medical hospital the
      incidence, causes and clinical impact of hyperamylasaemia and/or hyperlipasaemia
      in these patients. MATERIAL AND METHODS: During a 4-month period in 2004, amylase
      and lipase activities were measured in all patients (n, 1765) admitted to the
      Department of Internal Medicine of the Municipal Clinic of Luneburg, Germany.
      Patients with increased enzyme activities underwent abdominal ultrasonography
      and, if inconclusive, other imaging procedures. RESULTS: Amylase and/or lipase
      activities were increased in 140 (8%) patients with non-pancreatic diseases:
      amylase in 29 cases (21%) and 1 case (1%)<3 and>3 times the upper limit of
      normal, respectively, lipase in 120 cases (86%) and 6 cases (4%)<3 and>3 times,
      respectively. In 53 (38%) patients no further imaging studies could be performed.
      In the remaining 87 patients amylase was increased in 18 patients (21%) and
      lipase in 3 patients (3%). The pancreas was normal on imaging procedures in 77
      (89%) patients and abnormal in 10 (11%) (chronic pancreatitis: 4, small cystic
      lesions: 6). The cystic lesions were mostly located in the pancreas head,
      probably corresponding to branch-duct intraductal papillary mucinous neoplasm.
      CONCLUSIONS: Increased pancreatic enzyme activities occur in 8% of hospitalized
      patients with non-pancreatic diseases, but pancreatic abnormalities will be found
      in only a few (11%), which are unlikely to need further investigation or therapy.
      Therefore, routine analysis of amylase or lipase activities in patients with non
      pancreatic diseases is not indicated.

PMID- 18819040
TI  - A fatal case of encephalitis associated with Chikungunya virus infection.
AB  - An outbreak of Chikungunya fever occurred in north-east Italy in the summer of
      2007. Only 1 fatal case was observed, in an 83-y-old male hospitalized with
      encephalitis. Viral genome was detected at high level (1.5 x 10(8) copies/ml) in
      the cerebrospinal fluid 7 d after symptoms onset.

PMID- 18819041
TI  - Poor outcome in patients with spine-related leg or arm pain who are involved in
      compensation claims: a prospective study of patients in the secondary care
      sector.
AB  - OBJECTIVE: To investigate whether poor outcome after spinal pain episodes is
      linked with the claim process and, if so, whether this link is independent of
      other potential risk factors of chronic pain and disability in patients with
      spine-related leg or arm pain. METHODS: A 1-year prospective outcome study with
      internal control groups in two Danish secondary care, public, multidisciplinary,
      non-surgical spine clinics. Patients with low back pain (LBP) radiating to the
      leg (n = 1243) or with neck and arm pain thought to emanate from the neck (n =
      202) were referred to the clinics by their general practitioners.
      Rheumatologists, physiotherapists, and nurses examined, treated, and informed the
      patients based on cognitive principles. Follow-up data were collected with a
      postal questionnaire. Claim, defined as seeking some sort of financial
      compensation or filing any sort of financial claim, such as workers'
      compensation, was the main independent variable. Potential confounders examined
      were: age, sex, social class, smoking, duration and severity of pain and
      disability. The main outcome measures were: global assessment (main outcome
      variable), pain, disability, and intake of analgesics. RESULTS: Financial claims
      were registered by 31% of patients. After adjustment for covariates, the odds
      ratio for claim and no improvement was calculated to be 4.2 (95% CI 2.8-6.2) for
      the LBP/leg patients and 17.4 (95% CI 5.1-60.1) for the neck/arm patients.
      CONCLUSION: A claim for financial compensation is strongly and independently
      linked with a poor prognosis for Danish patients with pain radiating from the low
      back or neck.

PMID- 18819042
TI  - [Cardiology: challenges in practice and clinic].

PMID- 18819043
TI  - [Incidents of malfunction of mechanical heart valves as reported to the German
      Medical Devices Vigilance System].
AB  - BACKGROUND: The purpose of this study was to collect the experience gained from
      risk assessment of incidents associated with mechanical heart valves as reported
      to the German Medical Devices Vigilance System. METHODS: All events in connection
      with the use of prosthetic heart valves which had been reported to the Federal
      Institute for Drugs and Medical Products were identified in the Institute's
      anonymized database. Subsequently all information that had been obtained and the
      reports of investigations by the various responsible manufacturer of medical
      products were retrospectively analysed. RESULTS: Of 53 incident reports the
      aortic valve position was involved 32 times, the mitral valve position 21 times.
      17 cases of leaflet breakage, 12 of leaflet dysfunction, 6 of valve thrombosis, 4
      of paravalvular leakage, 4 of damage to the suture ring, 3 of endocarditis and 7
      of various other singular defects were reported. The outcome was mostly very
      serious (re-surgery, prolongation of surgery, death). Corrective actions taken by
      the manufacturers consisted of recalls, advisory notices and stoppage of
      production. CONCLUSIONS: The Medical Devices Vigilance System is able to detect
      product failures of mechanical heart valves and to initiate corrective action. As
      the reporting rate over more than 10 years is relatively low, it can be assumed
      that in general mechanical heart valves are safe medical devices. The quality of
      incident reporting by manufactures and users of medical devices should be
      improved to reduce the number of undetected and unsolved incidents.

PMID- 18819044
TI  - [Severe myocardial infarction due to late and very late stent thrombosis after
      coronary artery stenting with drug-eluting stents].
AB  - HISTORY AND ADMISSION FINDINGS: Two men, 59 and 65 years old, both with coronary
      heart disease, were admitted to hospital with acute ST-segment elevation
      myocardial infarction. They both had undergone coronary artery stenting with drug
      eluting stents 9 months and 3 years before, respectively. After stent
      implantation combined antiplatelet therapy with acetylsalicylic acid and
      clopidogrel had been administered for 6 and 18 months, respectively. Clopidogrel
      had been stopped 10 weeks ago in patient 1 and 18 months ago in patient 2.
      INVESTIGATIONS AND DIAGNOSIS: Cardiac catheterization revealed in both cases the
      diagnosis of stent thrombosis in the drug-eluting stent. TREATMENT AND COURSE:
      After successful intervention, both patients were relieved of their symptoms. The
      total creatinkinase reached a maximum of 4150 U/l and 3185 U/l, respectively,
      representing severe myocardial infarction in both cases. CONCLUSION: Myocardial
      infarction is common in patients with a history of coronary artery disease.
      Especially after coronary artery stenting with drug-eluting stents, severe
      myocardial infarction due to stent thrombosis may occur late after stent
      implantation and be independent of changes in antiplatelet therapy. These
      patients and physicians should therefore be fully aware of this risk and of the
      crucial importance of antiplatelet therapy after coronary artery stenting.

PMID- 18819045
TI  - [Outpatient or inpatient treatment of acute coronary syndrome? Pro outpatient
      treatment].

PMID- 18819046
TI  - [Outpatient or inpatient treatment of acute coronary syndrome? Pro intpatient
      treatment].

PMID- 18819047
TI  - [Surgical or interventional aortic valve repair? Pro surgical repair].

PMID- 18819048
TI  - [Surgical or interventional aortic valve repair? Pro interventional repair].

PMID- 18819049
TI  - [Historical perspectives on reperfusion therapy in acute myocardial infarction.
      The 30th anniversary of acute percutaneous coronary intervention].

PMID- 18819050
TI  - [Arrhythmia in a patient without cardiac disease].

PMID- 18819051
TI  - [What to do in the case of newly-occurring atrial fibrillation?].

PMID- 18819052
TI  - [Telemedicine--ready for use in the cardiological field?].
AB  - The changes in the demographic structure, the increasing multi-morbidity in
      connection with a rise in the number of chronic illnesses and the absence of an
      effective coordination of the different levels of health care services with its
      discontinuous processes and redundancies will increase the economic burdens in
      the health care system. The latest developments and appropriate logistic premises
      nowadays offer a realistic basis for implementing telemonitoring as a central
      service and information tool as well as an instrument controlling the information
      and data-flow between patient, hospital and medical practitioner.

PMID- 18819053
TI  - Contrasting effects of eplerenone and spironolactone on adrenal cell
      steroidogenesis.
AB  - Spironolactone and eplerenone are widely used as mineralocorticoid antagonists.
      Spironolactone has several nonspecific actions including inhibition of androgen
      receptor and steroid hormone biosynthesis. While studies have shown that
      eplerenone does not exhibit nonspecific actions on androgen receptor, its effects
      on steroid hormone production have not been reported. Herein, the effects of
      eplerenone (0.1-30 microM) and spironolactone (0.1-30 microM) on steroid
      production were examined in human adrenocortical H295R cells. Spironolactone
      inhibited basal production of cortisol (91%) and aldosterone (53%). Treatment of
      H295R cells with angiotensin II (Ang II) for 24 h increased aldosterone
      production by 11-fold. Spironolactone inhibited Ang II stimulation of aldosterone
      production by 80%. Addition of pregnenolone increased aldosterone (9-fold) and
      cortisol (3-fold) production. Spironolactone inhibited pregnenolone metabolism to
      aldosterone (67%) and cortisol (74%). The inhibitory effects of spironolactone
      occurred at concentrations far higher than those needed to block
      mineralocorticoid receptor, suggesting an action directly on the enzymes involved
      in steroid production. In contrast, eplerenone did not inhibit basal, Ang II,
      forskolin, pregnenolone-stimulated cortisol, or aldosterone production. Together,
      these data demonstrate that opposed to spironolactone, pharmacologic
      concentrations of eplerenone do not inhibit adrenal cell aldosterone or cortisol
      production.

PMID- 18819054
TI  - DAX-1A (NR0B1A) expression levels are extremely low compared to DAX-1 (NR0B1) in
      human steroidogenic tissues.
AB  - The orphan nuclear receptor DAX-1 (dosage-sensitive sex reversal-AHC critical
      region on the X chromosome gene 1; NR0B1) is known for its role in human
      development, specifically sex determination and steroidogenesis. Several recent
      publications have described an alternatively spliced form of DAX-1 called DAX-1A
      ( NR0B1A). DAX-1A is encoded by exons 1 and 2A of DAX-1, with exon 2A located
      within the DAX-1 intron 1. DAX-1A expression has been observed in several
      tissues, including adrenal gland, ovary, and testis. Transfection studies have
      further shown that DAX-1A has an inhibitory effect on DAX-1, suggesting a role
      for DAX-1A in the regulation of adrenal and gonadal differentiation/function.
      However, the relative level of DAX-1 versus DAX-1A transcripts still remains
      unclear. Herein, we developed and performed quantitative real-time RT-PCR to
      measure DAX-1 and DAX-1A mRNA expression levels in H295R human adrenal carcinoma
      cell lines, human adult and fetal adrenal glands, corpus luteum, testis, whole
      pre- and postmenopausal ovaries, ovarian follicles, placenta, liver, and kidney.
      These mRNA expression levels were quantified using DAX-1 and DAX-1A standard
      curves. In addition, Western blotting analysis was performed to examine both DAX
      1 and DAX-1A protein levels in H295R cells, adrenal glands, corpus luteum, and
      liver. Both DAX-1 and DAX-1A mRNA were detected in all samples of H295R cells,
      human fetal and adult adrenals, testis, ovary, ovarian follicles, and corpus
      luteum. However, DAX-1 mRNA levels were significantly higher (> 37-fold) than
      that seen for DAX-1A (p<0.01). DAX-1A mRNA expression levels were undetectable in
      human liver, placenta, and kidney. Western blotting analysis results demonstrated
      that DAX-1 protein was predominantly expressed in H295R cells, human adult
      adrenal, and corpus luteum. These results suggest that in comparison to DAX-1A,
      DAX-1 is, by far, the predominant mRNA isoform found in human adrenal glands and
      gonads.

PMID- 18819055
TI  - Sex- and depot-specific lipolysis regulation in human adipocytes: interplay
      between adrenergic stimulation and glucocorticoids.
AB  - The purpose of this investigation was to explore interactions between adrenergic
      stimulation, glucocorticoids, and insulin on the lipolytic rate in isolated human
      adipocytes from subcutaneous and omental fat depots, and to address possible sex
      differences. Fat biopsies were obtained from 48 nondiabetic subjects undergoing
      elective abdominal surgery. Lipolysis rate was measured as glycerol release from
      isolated cells and proteins involved in lipolysis regulation were assessed by
      immunoblots. Fasting blood samples were obtained and metabolic and inflammatory
      variables were analyzed. In women, the rate of 8-bromo-cAMP- and isoprenaline
      stimulated lipolysis was approximately 2- and 1.5-fold higher, respectively, in
      subcutaneous compared to omental adipocytes, whereas there was no difference
      between the two depots in men. Dexamethasone treatment increased the ability of 8
      bromo-cAMP to stimulate lipolysis in the subcutaneous depot in women, but had no
      consistent effects in fat cells from men. Protein kinase A, Perilipin A, and
      hormone sensitive lipase content in adipocytes was not affected by adipose depot,
      sex, or glucocorticoid treatment. In conclusion, catecholamine and glucocorticoid
      regulation of lipolysis in isolated human adipocytes differs between adipose
      tissue depots and also between sexes. These findings may be of relevance for the
      interaction between endogenous stress hormones and adipose tissue function in
      visceral adiposity and the metabolic syndrome.

PMID- 18819056
TI  - The fatty acid amide hydrolase (FAAH) Pro129Thr polymorphism is not associated
      with severe obesity in Greek subjects.
AB  - Fatty amid acid hydrolase (FAAH) has been implicated at both protein and gene
      level with obesity. An association between Pro129Thr variant of the FAAH gene and
      obesity has been described, but various studies have yielded conflicting results.
      Our aim was to determine whether this polymorphism is related to severe obesity
      and whether it confers a risk for variability of quantitative metabolic traits in
      a cohort of Greek obese subjects. Two groups of severely obese subjects (BMI > 40
      kg/m (2)) were studied: a group of 158 metabolically healthy and a group of 145
      obese subjects with metabolic syndrome, which were compared to a control group
      consisting of 121 lean individuals. We did not find any association between the
      Pro129Thr polymorphism with severe obesity in both subgroups of obese subjects,
      between these two subgroups (p= 0.11) or on basic anthropometric characteristics
      in the three groups. Statistically significant differences were found for glucose
      and HDL in metabolically healthy subjects and HDL in the control group. The
      borderline significant p-values were not significant after correction for
      multiple testing. We were unable to find robust evidence of an association of the
      Pro129Thr variant with severe obesity, and any related quantitative traits among
      the obese Greek subjects examined.

PMID- 18819057
TI  - Testosterone and bioavailable testosterone help to distinguish between mild
      Cushing's syndrome and polycystic ovarian syndrome.
AB  - Women with Cushing's syndrome (CS) and polycystic ovarian syndrome (PCOS) may
      present with similar symptoms. Subjects with mild CS lack clinical stigmata of
      classical CS and often have normal laboratory tests measuring hypercortisolism.
      Thus, distinguishing mild CS from PCOS may be difficult. We hypothesized that
      either total testosterone (TT) or bioavailable testosterone (BT) levels or the
      calculation of the free androgen index (FAI) would be low in patients with mild
      CS and elevated in patients with PCOS, and could help differentiate the two
      conditions. TT, BT, and FAI were measured in a group of 20 patients of
      reproductive age with mild CS and 20 PCOS patients matched for age and BMI. We
      used receiver operator characteristic (ROC) curves to assess the sensitivity and
      specificity of these measurements for the diagnosis of CS. TT (p<0.0001), BT
      (p=0.02), and FAI (p=0.003) were significantly elevated in PCOS patients compared
      to mild CS patients. Sex hormone-binding globulin was similar in both groups. The
      optimal cut-point for TT was 1.39 nmol/L, yielding a sensitivity of 95% and a
      specificity of 70%. The cut-point for BT was 0.24 nmol/L, resulting in a
      sensitivity of 75% and a specificity of 80%. The cut-point for FAI was 5.7, with
      a sensitivity of 88% and a specificity of 60%. We conclude that TT levels may be
      useful to discriminate between mild CS and PCOS. In patients with signs and
      symptoms consistent with CS and PCOS, a TT level of <1.39 nmol/L warrants a
      workup for CS.

PMID- 18819058
TI  - Effects of antidiabetic drugs on glucose tolerance in streptozotocin-nicotinamide
      induced mildly diabetic and streptozotocin-induced severely diabetic mice.
AB  - In this study, streptozotocin-nicotinamide-induced mildly diabetic mice and
      streptozotocin-induced severely diabetic mice were created to compare their
      characteristics and to investigate the effects of antidiabetic drugs on glucose
      tolerance. In severely diabetic mice, the pancreatic insulin content decreased to
      approximately 10% of levels found in normal mice. These mice also showed a
      decrease in body weight, a marked increase in nonfasting blood glucose levels and
      urinary glucose excretion, and a marked decline in glucose tolerance due to
      insulin secretory deficiency. In contrast, the pancreatic insulin content was
      approximately 50% of normal levels in mildly diabetic mice. These mice did not
      show any change in body weight, but displayed a mild increase in nonfasting blood
      glucose levels and urinary glucose excretion, and a mild decline in glucose
      tolerance due to loss of early-phase insulin secretion. Administration of
      antidiabetic drugs, namely voglibose, metformin, glibenclamide, sitagliptin and
      insulin, significantly improved glucose tolerance in mildly diabetic mice. In
      severely diabetic mice, voglibose, metformin and insulin significantly improved
      glucose tolerance, but no significant effect was observed for glibenclamide and
      sitagliptin due to a decreased insulinotropic effect. These results demonstrate
      that streptozotocin-nicotinamide-induced mildly diabetic mice have many
      pathological features resembling type 2 diabetes, and can serve as models for the
      pharmacological evaluation of many antidiabetic drugs.

PMID- 18819059
TI  - Endoscopic full-thickness resection of gastric tumors using a novel grasp-and
      snare technique: feasibility in ex vivo and in vivo porcine models.
AB  - BACKGROUND AND STUDY AIMS: Endoscopic full-thickness resection (EFTR) is a less
      invasive method of en bloc removal of gastrointestinal tract tumors. The aim of
      this study was to evaluate the feasibility of a grasp-and-snare EFTR technique
      using a novel tissue-lifting device that provides more secure tissue anchoring
      and manipulation. METHODS: EFTR of normal gastric tissue and model stomach tumors
      was performed using a double-channel therapeutic endoscope with a prototype
      tissue-lifting device through one channel and a prototype hexagonal snare through
      the other. The lifting device was advanced through the open snare and anchored to
      the gastric wall immediately adjacent the model tumor. The tissue-lifting device
      was then partially retracted into the endoscope, causing the target tissue,
      including tumor, to evert into the gastric lumen. The open snare was then placed
      distal to the tumor around uninvolved gastric tissue. Resection was performed
      with a blended electrosurgical current through the snare. In the live pigs, EFTR
      was followed by laparotomy to asses for complications. RESULTS: 24 EFTRs were
      performed -- 14 in explanted stomachs and 10 in live pigs. In total, 23/24
      resections resulted in full-thickness gastric defects. Resection specimens
      measured up to 5.0 cm when stretched and pinned on a histology stage. Gross
      margins were negative in 17/20 model tumor resections. Two resections were
      complicated by gastric mural bleeding. There was no evidence of adjacent organ
      injury. CONCLUSIONS: EFTR of gastric tumors using the grasp-and-snare technique
      is feasible in pigs. This technique is advantageous in that eversion of the
      gastric wall avoids injury to external organs, continuous luminal insufflation is
      not required, and the involved techniques are familiar to endoscopists.
      Additional research is necessary to further evaluate safety and reliable closure.

PMID- 18819060
TI  - Single-operator method for double-balloon endoscopy: a pilot study.
AB  - Double-balloon endoscopy (DBE) is a new technique that allows diagnosis and
      treatment throughout the entire small intestine. We have recently developed a
      method that allows a single operator to perform DBE, by employing "grip and
      pinch" and "hold (or 'keep') and slide" techniques. This one-person method
      obviates the need for two operators who must cooperate closely.

PMID- 18819061
TI  - Tumor formation following murine neural precursor cell transplantation in a rat
      peripheral nerve injury model.
AB  - Neural stem cells show a remarkable aptitude for integration and appropriate
      differentiation at sites of cellular injury in central nervous system (CNS)
      disease models. In contrast, reports of neural stem cell applications in
      peripheral nerve injury models are sparse. In this study we sought to determine
      if the C17.2 cell line would respond to cues in the microenvironment of the
      injured peripheral nerve and enhance neuronal regeneration in rodent sciatic
      nerve injury models. We transplanted C17.2 into several sciatic nerve injury
      models in 45 nude rats, including nerve transection, nerve crush, and nerve gap
      models. Twelve of the animals in this study developed large tumors at the site of
      neural stem cell transplants. Histologically, the tumors resembled
      neuroblastomas. The tumors were confirmed to be of transplanted cell origin by
      positive beta-galactosidase staining. Tumors occurred only in models where the
      nerve remained intact or where continuity of the nerve was restored. We concluded
      that C17.2 transplantation into peripheral nerve injury models resulted in a high
      rate of tumor formation. This study demonstrates that the success of neural
      precursor transplants in the CNS cannot necessarily be extrapolated to the
      peripheral nervous system.

PMID- 18819062
TI  - Small intestinal perforation of endoscopically unrecognized lesions during
      peroral single-balloon enteroscopy.

PMID- 18819063
TI  - Removal of a doubly impacted plastic stent: a new technique.

PMID- 18819064
TI  - Unusual cause for dysphagia: perforation of the proximal esophagus by a
      toothpick.

PMID- 18819065
TI  - Endoscopic clip closure of penetrating stab wound to stomach.

PMID- 18819066
TI  - Forgotten biliary endoprosthesis. "Follow up" after 10 years.

PMID- 18819067
TI  - Endoscopic submucosal dissection for residual rectal polyps embedded in tissue
      scar: a "rescue therapy" to prevent surgical intervention?

PMID- 18819068
TI  - Endoscopic GIST resection using FlushKnife ESD and subsequent perforation closure
      by means of endoscopic full-thickness suturing.

PMID- 18819069
TI  - Double pylorus secondary to recurrent ulcer: serial endoscopy follow-up.

PMID- 18819072
TI  - Enhanced B-cell activation mediated by TLR4 and BCR crosstalk.
AB  - Despite the important role of B lymphocytes as a bridge between the innate and
      the adaptive immune system, little is known regarding lipopolysaccharide (LPS)
      recognition, activation of signalling networks or conceivable cooperation between
      LPS and the B-cell antigen receptor (BCR). Here, we show that primary B cells can
      efficiently discriminate between different LPS chemotypes, responding with at
      least 100-fold higher sensitivity to rough-form LPS compared with smooth-form
      LPS. Using genetically modified mice, we demonstrate that B lymphocytes recognize
      all LPS chemotypes via Toll-like receptor 4 (TLR4). In addition, we dissect the
      signalling pathways that lead to CD69 upregulation upon TLR4 and BCR activation
      in primary B cells. Our data suggest that TLR4 and BCR induce CD69 transcription
      via two distinct sets of signalling molecules, exerting quantitative and
      qualitative differences in B-cell activation. Finally, we show that simultaneous
      stimulation of TLR4 and BCR additively elevates B-cell activation. In contrast,
      co-engagement of TLR4 and BCR by antigen-coupled LPS synergistically enhances
      activation of B cells, pointing out attractive targets for signalling crosstalk
      in B lymphocytes.

PMID- 18819071
TI  - T-bet expression by dendritic cells is required for the repolarization of
      allergic airway inflammation.
AB  - By cross-linking B7-DC on dendritic cells (DC) the human IgM antibody (B7-DC XAb)
      shifts polarized immune responses from Th2 to Th1 in an antigen-specific manner.
      The molecular determinants governing the ability of DC to reprogram the polarity
      of T cell recall responses are not yet known. In addition to the expected role of
      T-bet expressed by T cells in regulating Th1 responses, we find using in vitro
      assays and an established in vivo model of allergic airway inflammation that T
      bet expression by DC is also required for the polarity shift promoted by B7-DC
      XAb. T-bet expression by both T cells and DC is critically important for B7-DC
      XAb-induced down-regulation of IL-4, up-regulation of IFN-gamma and suppression
      of allergic airway inflammation. Moreover, retroviral reconstitution of T-bet
      expression in T-bet-deficient DC rescued their ability to modulate both naive and
      memory T-cell responses from Th2 to Th1. Our observations further our
      understanding of the critical mediators controlling the ability of DC to modify
      the responses of previously activated T cells and reveal the interesting use of
      the same transcription factor to regulate the inductive phenotype of DC and the
      inducible phenotype of T cells.

PMID- 18819073
TI  - Endothelial function in patients with and without diabetes mellitus with
      different degrees of coronary artery stenosis.
AB  - PURPOSE: To evaluate endothelial function using flow-mediated dilatation (FMD) of
      the brachial artery in patients with and without diabetes mellitus (DM) with
      different degrees of coronary artery stenosis. METHOD: We investigated 293
      patients, 69 (23.6%) of whom had DM. FMD and coronary arteriography were
      performed. RESULTS: Patients with DM had a significantly lower FMD (mean +/- SD,
      3.7 +/- 3.8%) compared with patients without DM (mean +/- SD, 5.2 +/- 5.3%) (p <
      0.05). When the results were broken down by the severity of coronary artery
      disease (CAD) (no significant coronary artery stenosis, 1-vessel disease, 2
      vessel disease, and 3-vessel disease) the only statistically significant
      difference between diabetics and nondiabetics was found in patients without
      significant coronary stenosis (mean FMD +/- SD: 5.2 +/- 4.4% in diabetics, 7.6 +/
      5.4% in nondiabetics [p < 0.05]). CONCLUSION: In CAD patients, the presence of
      DM was associated with endothelial dysfunction. The difference in the FMD was
      clearly expressed between patients with and without DM in the subgroup without
      significant coronary stenosis, and was no longer present with advanced coronary
      atherosclerosis.

PMID- 18819074
TI  - PharmGKB: an integrated resource of pharmacogenomic data and knowledge.
AB  - The PharmGKB is a publicly available online resource that aims to facilitate
      understanding how genetic variation contributes to variation in drug response. It
      is not only a repository of pharmacogenomics primary data, but it also provides
      fully curated knowledge including drug pathways, annotated pharmacogene
      summaries, and relationships among genes, drugs, and diseases. This unit
      describes how to navigate the PharmGKB Web site to retrieve detailed information
      on genes and important variants, as well as their relationship to drugs and
      diseases. It also includes protocols on our drug-centered pathway, annotated
      pharmacogene summaries, and our Web services for downloading the underlying data.
      Workflow on how to use PharmGKB to facilitate design of the pharmacogenomic study
      is also described in this unit.

PMID- 18819075
TI  - Identifying protein domains with the Pfam database.
AB  - Pfam is a database of protein domain families, with each family represented by
      multiple sequence alignments and profile hidden Markov models (HMMs). In
      addition, each family has associated annotation, literature references, and links
      to other databases. The entries in Pfam are available via the World Wide Web and
      in flatfile format. This unit contains detailed information on how to access and
      utilize the information present in the Pfam database, namely the families,
      multiple alignments, and annotation. Details on running Pfam, both remotely and
      locally are presented.

PMID- 18819076
TI  - Data storage and analysis in ArrayExpress and Expression Profiler.
AB  - ArrayExpress at the European Bioinformatics Institute is a public database for
      MIAME-compliant microarray and transcriptomics data. It consists of two parts:
      the ArrayExpress Repository, which is a public archive of microarray data, and
      the ArrayExpress Warehouse of Gene Expression Profiles, which contains
      additionally curated subsets of data from the Repository. Archived experiments
      can be queried by experimental attributes, such as keywords, species, array
      platform, publication details, or accession numbers. Gene expression profiles can
      be queried by gene names and properties, such as Gene Ontology terms, allowing
      expression profiles visualization. The data can be exported and analyzed using
      the online data analysis tool named Expression Profiler. Data analysis
      components, such as data preprocessing, filtering, differentially expressed gene
      finding, clustering methods, and ordination-based techniques, as well as other
      statistical tools are all available in Expression Profiler, via integration with
      the statistical package R.

PMID- 18819077
TI  - The Gene Ontology (GO) project: structured vocabularies for molecular biology and
      their application to genome and expression analysis.
AB  - Scientists wishing to utilize genomic data have quickly come to realize the
      benefit of standardizing descriptions of experimental procedures and results for
      computer-driven information retrieval systems. The focus of the Gene Ontology
      project is three-fold. First, the project goal is to compile the Gene Ontologies:
      structured vocabularies describing domains of molecular biology. Second, the
      project supports the use of these structured vocabularies in the annotation of
      gene products. Third, the gene product-to-GO annotation sets are provided by
      participating groups to the public through open access to the GO database and Web
      resource. This unit describes the current ontologies and what is beyond the scope
      of the Gene Ontology project. It addresses the issue of how GO vocabularies are
      constructed and related to genes and gene products. It concludes with a
      discussion of how researchers can access, browse, and utilize the GO project in
      the course of their own research.

PMID- 18819078
TI  - Exploring biological networks with Cytoscape software.
AB  - Cytoscape is a free software package for visualizing, modeling, and analyzing
      molecular and genetic interaction networks. As a key feature, Cytoscape enables
      biologists to determine and analyze the interconnectivity of a list of genes or
      proteins. This unit explains how to use Cytoscape to load and navigate biological
      network information and view mRNA expression profiles and other functional
      genomics and proteomics data in the context of the network obtained for genes of
      interest. Additional analyses that can be performed with Cytoscape are also
      discussed.

PMID- 18819079
TI  - Browsing multidimensional molecular networks with the generic network browser (N
      Browse).
AB  - N-Browse is a graphical network browser for the visualization and navigation of
      heterogeneous molecular interaction data. N-Browse runs as a Java applet in a Web
      browser, providing highly dynamic and interactive on-demand access to network
      data available from a remote server. The N-Browse interface is easy to use and
      accommodates multiple types of functional linkages with associated information,
      allowing the exploration of many layers of functional information simultaneously.
      Although created for applications in biology, N-Browse uses a generic database
      schema that can be adapted to network representations in any knowledge domain.
      The N-Browse client-server package is freely available for distribution,
      providing a convenient way for data producers and providers to distribute and
      offer interactive visualization of network-based data.

PMID- 18819080
TI  - Thin-layer chromatography.
AB  - TLC is used extensively in nucleic acid chemistry to monitor the progress of
      chemical reactions, to assay fractions collected from a larger chromatographic
      separation (e.g., column chromatography), and to determine optimal conditions
      prior to column chromatography. This unit describes methods for spotting test
      compounds onto a TLC plate, developing the plate in a suitable solvent system,
      visualizing the results, and calculating the retention factor (R(f)). Candidate
      compounds can be co-spotted for identification without relying on R(f) values.

PMID- 18819081
TI  - RNA intramolecular dynamics by single-molecule FRET.
AB  - Investigation of single RNA molecules using fluorescence resonance energy
      transfer (FRET) is a powerful approach to investigate dynamic and thermodynamic
      aspects of the folding process of a given RNA. Its application requires
      interdisciplinary work from the fields of chemistry, biochemistry, and physics.
      The present work gives detailed instructions on the synthesis of RNA molecules
      labeled with two fluorescent dyes interacting by FRET, as well as on their
      investigation by single-molecule fluorescence spectroscopy.

PMID- 18819082
TI  - Synthesis of fluoroneplanocin A.
AB  - Fluoroneplanocin A, designed as a potent mechanism-based irreversible inhibitor
      of S-adenosylhomocysteine hydrolase (SAH), is synthesized from D-ribose via a key
      D-cyclopentenone intermediate. This intermediate is synthesized using a
      stereoselective Grignard reaction, a ring-closing metathesis (RCM) reaction, and
      oxidative rearrangement as key steps.

PMID- 18819083
TI  - Chemical synthesis of oligoribonucleotides with 2'-O-(2-cyanoethoxymethyl)
      protected phosphoramidites.
AB  - An RNA synthetic method with 2-cyanoethoxymethyl (CEM) as the 2'-hydroxyl
      protecting group allows the synthesis of long oligoribonucleotides from CEM
      amidites with an efficiency and final purity comparable to that obtained in DNA
      synthesis. The CEM-amidites give a high coupling efficiency, because the CEM
      group minimizes steric hindrance in the coupling reaction. The CEM group shows
      satisfactory stability under solid-phase synthetic conditions, avoids the
      generation of asymmetric centers, and is easily cleaved to give the final
      product. This unit describes the synthesis of the four CEM-amidites, the
      preparation of reagents, the solid-phase synthesis of oligoribonucleotides on an
      automated DNA synthesizer, and their deprotection.

PMID- 18819084
TI  - Hematopoietic differentiation of human embryonic stem cells by cocultivation with
      stromal layers.
AB  - Human embryonic stem (hES) cells are of remarkable interest both for the utility
      of these cells for studying basic human developmental biology and as a potential
      source for novel therapeutics. Here, we provide detailed methodologies of one of
      the first systems used to mediate differentiation of hES cells--stromal cell
      coculture. Use of stromal cells adds the ability to manipulate aspects of the
      developmental niche that support differentiation into a defined lineage. These
      methods will allow efficient and reproducible development of hematopoietic
      progenitor cells, as well as potentially mature hematopoietic cells that are
      suitable for subsequent in vitro and in vivo studies.

PMID- 18819085
TI  - Isolating, expanding, and infecting human and rodent fetal neural progenitor
      cells.
AB  - Neural progenitor cells have tremendous utility for understanding basic
      developmental processes, disease modeling, and therapeutic intervention. The
      protocols described in this unit provide detailed information to isolate and
      expand human and rodent neural progenitor cells in culture for several months as
      floating aggregates (termed neurospheres) or plated cultures. Detailed protocols
      for cryopreservation, neural differentiation, exogenous gene expression using
      lentivirus, and transplantation into the rodent nervous system are also
      described.

PMID- 18819086
TI  - Endothelial differentiation of embryonic stem cells.
AB  - Vascular progenitor cells derived from stem cells could potentially lead to a
      variety of clinically relevant applications, including cell-based therapies and
      tissue engineering. Here, we describe methods for isolating purified
      proliferating populations of vascular endothelial cells from mouse embryonic stem
      cells (mESC) using Flk-1 positive sorted cells, VEGF supplementation, and a
      rigorous manual selection technique required for endothelial cell purification
      and expansion. Using this in vitro derivation procedure, it is possible to obtain
      millions of cells at various stages of differentiation, with the potential for up
      to 25 population doublings.

PMID- 18819087
TI  - Use of hyaluronan-derived hydrogels for three-dimensional cell culture and tumor
      xenografts.
AB  - The practice of in vitro three-dimensional (3-D) cell culture has lagged behind
      the realization that classical two-dimensional (2-D) culture on plastic surfaces
      fails to mirror normal cell biology. Biologically, a complex network of proteins
      and proteoglycans that constitute the extracellular matrix (ECM) surrounds every
      cell. To recapitulate the normal cellular behavior, scaffolds (ECM analogs) that
      reconstitute the essential biological cues are required. This unit describes the
      3-D cell culture and tumor engineering applications of Extracel, a novel
      semisynthetic ECM (sECM), based on cross-linked derivatives of hyaluronan and
      gelatin. A simplified cell encapsulation and pseudo-3-D culturing (on top of
      hydrogels) protocol is provided. In addition, the use of this sECM as a vehicle
      to obtain tumor xenografts with improved take rates and tumor growth is
      presented. These engineered tumors can be used to evaluate anticancer therapies
      under physiologically relevant conditions.

PMID- 18819088
TI  - Matrix metalloproteinases.
AB  - Matrix metalloproteinases are a class of enzymes that play an important role in
      the remodeling of the extracellular matrix in development and cancer metastasis.
      This unit describes a set of methods--cell-mediated dissolution of type-1
      collagen fibrils, direct and reverse zymography, enzyme capture based on alpha2
      macroglobulin and TIMP-1 and -2, and demonstration of cryptic thiol groups in
      metalloproteinase precursors--that are used to characterize the functions of
      matrix metalloproteinases and their inhibitors.

PMID- 18819089
TI  - Analysis of endocytic trafficking by single-cell fluorescence ratio imaging.
AB  - The post-endocytic sorting of internalized membrane proteins plays a critical
      role in numerous physiological processes, including receptor desensitization,
      degradation of non-native plasma membrane proteins, and cell surface retrieval of
      receptors from early endosomes upon ligand dissociation. Here, we describe a
      fluorescence ratiometric image analysis (FRIA) method used to determine the post
      endocytic fate and transport kinetics of transmembrane proteins based on the pH
      measurement of internalized cargo-containing compartments in living cells. The
      method relies on the notion that the pH of a cargo-containing transport vesicle
      (vesicular pH, pH(v)) could be taken as an indicator of its identity, considering
      that endocytic organelles (e.g., sorting endosome, recycling endosome, late
      endosome/MVB, and lysosome) have characteristic pH(v). The pH-sensitive FITC
      conjugated secondary antibody is attached to the cargo via a primary antibody,
      recognizing the cargo extracellular domain. The pH(v) is determined by single
      cell FRIA. Internalized cargo colocalization with organellar markers, as well as
      pH(v) measurement of recycling endosome, lysosome, and the TGN are discussed to
      validate the technique and facilitate data interpretation.

PMID- 18819090
TI  - Making giant unilamellar vesicles via hydration of a lipid film.
AB  - This unit describes protocols for making giant unilamellar vesicles (GUVs) based
      on rehydration of dried lipid films. These model membranes are useful for
      determining the impact of membrane and membrane-binding components on lipid
      bilayer stiffness and phase behavior. Due to their large size, they are
      especially amenable to studies using fluorescence and light microscopy, and may
      also be manipulated for mechanical measurements with optical traps or
      micropipets. In addition to their use in encapsulation, GUVs have proven to be
      useful model systems for studying many cellular processes, including tubulation,
      budding, and fusion, as well as peptide insertion. The introduction of enzymes or
      proteins can result in reorganization, leading to such diverse behavior as
      vesicle aggregation, fusion, and fission.

PMID- 18819091
TI  - Purification of intact chloroplasts from Arabidopsis and spinach leaves by
      isopycnic centrifugation.
AB  - Chloroplasts are plant-specific organelles. They are the site of photosynthesis
      but also of many other essential metabolic pathways, such as syntheses of amino
      acids, vitamins, lipids, and pigments. This unit describes the isolation and
      purification of chloroplasts from Arabidopsis and spinach leaves. Differential
      centrifugation is first used to obtain a suspension enriched in chloroplasts
      (crude chloroplasts extract). In a second step, Percoll density gradient
      centrifugation is used to recover pure and intact chloroplasts. The Basic
      Protocol describes the purification of chloroplasts from Arabidopsis leaves. This
      small flowering plant is now widely used as a model organism in plant biology as
      it offers important advantages for basic research in genetics and molecular
      biology. The Alternate Protocol describes the purification of chloroplasts from
      spinach leaves. Spinach, easily available all through the year, remains a model
      of choice for the large-scale preparation of pure chloroplasts with a high degree
      of intactness.

PMID- 18819092
TI  - Hemostatic complications of angiogenesis inhibitors in cancer patients.
AB  - Tumor vasculature and tumor-associated neo-angiogenesis have recently become
      major targets for rational drug design of antineoplastic agents. Five such agents
      with angiogenesis inhibiting activity (thalidomide, lenalidomide, bevacizumab,
      sunitinib, sorafenib) have already obtained US Food and Drug Administration
      approval for clinical use and many others have entered clinical trials. Vascular
      complications, including venous or arterial thromboembolism and hemorrhage, have
      emerged as relevant toxicities in several clinical trials with angiogenesis
      inhibitors. Given the well-known interplay between the blood clotting system,
      angiogenesis, and tumor growth, a better understanding of the impact of these new
      drugs on overall hemostatic balance is required. In this brief overview, we
      discuss the incidence of hemostatic complications, the likely pathogenetic
      mechanisms involved, and the critical need to establish in randomized clinical
      trials the usefulness of thrombosis prophylaxis to prevent these complications.
      Careful documentation of hemostatic complications during treatment with each of
      the new antiangiogenic drugs is warranted. Further studies are urgently required
      to better define the causal association of these new agents with hemostatic
      complications and to establish the best prophylactic strategy.

PMID- 18819093
TI  - A benchmark analysis of the achievement of therapeutic goals for type 1 Gaucher
      disease patients treated with imiglucerase.
AB  - To assess the extent to which patients with type 1 Gaucher disease (GD1)
      receiving individualized enzyme replacement therapy with imiglucerase attain six
      defined therapeutic goals. One hundred and ninety-five GD1 patients enrolled in
      the ICGG Gaucher Registry, all of whom had data available for hemoglobin,
      platelet count, liver volume, spleen volume, bone pain, and bone crises at first
      infusion and after 4 years of therapy with imiglucerase, were evaluated for
      achievement of published therapeutic goals. The proportion of patients who met
      all six therapeutic goals increased from 2.1% at first infusion to 41.5% at 4
      years; > or =5 goals from 12.8% to 76.9%; > or =4 goals from 37.4% to 92.8%; > or
      =3 goals from 70.8% to 99.0%; and > or =2 goals from 95.4% to 99.5%. All patients
      met at least one goal at first infusion and after 4 years of treatment. The
      proportion of patients meeting specific therapeutic goals increased for all
      parameters between first infusion and 4 years of therapy: platelet count (24.6%
      79.5%), spleen volume (25.6%-78.5%), liver volume (45.6%-90.8%), bone pain (62.6
      70.3%), hemoglobin (68.2-91.8%), and bone crises (91.8-99.0%). On average,
      patients who received higher doses of imiglucerase achieved a greater number of
      therapeutic goals. This analysis provides a benchmark for evaluating the utility
      of a disease management approach for GD1 based on monitoring achievement of
      therapeutic goals after treatment with imiglucerase.

PMID- 18819094
TI  - Sibling history of asthma is a risk factor for pain in children with sickle cell
      anemia.
AB  - The basis of the association between asthma and an increased rate of pain among
      children with sickle cell anemia (SCA) is unclear. To provide evidence for a
      familial contribution to this observation, we tested the hypothesis that a family
      history of asthma is associated with an increased pain rate. Using data from the
      Cooperative Study for Sickle Cell Disease (CSSCD), we identified 211 children
      with SCA with asthma history of the parents and siblings. A sibling history of
      asthma was associated with a greater rate of pain (mean rate ratio = 2.48, 95% CI
      = 1.6-4.0; P < 0.001) when compared with children without a sibling history of
      asthma. Parental history of asthma was not associated an increase rate of pain
      (mean ratio = 1.51, 95% CI= 0.92-2.62; P = 0.12). Further studies are needed to
      examine genetic and/or environmental risks for asthma as potential contributors
      to pain in children with SCA.

PMID- 18819095
TI  - Cardiopulmonary imaging, functional and laboratory studies in sickle cell disease
      associated pulmonary hypertension.
AB  - Pulmonary hypertension (PHT) occurs in approximately 30% of adults with sickle
      cell disease (SCD) and is an independent risk factor for early death. In this
      study, we aimed to determine the value of general laboratory testing, plain chest
      radiography, electrocardiography (ECG), high-resolution computer tomography
      (HRCT) of the thorax, pulmonary function testing, and plasma N-terminal brain
      natriuretic peptide (NT-proBNP) and brain natriuretic peptide (BNP) in patients
      with SCD-related PHT. A cohort of 85 ambulatory sickle cell patients were
      prospectively screened for PHT with echocardiography (defined as a tricuspid
      regurgitation flow velocity of > or =2.5 m/sec). All patients were systematically
      evaluated by the aforementioned diagnostic tests comparing patients with and
      without PHT. The prevalence of PHT was 41% in HbSS/HbSbeta(0)-thalassemia
      patients and 13% in HbSC/HbSbeta(+)-thalassemia patients. No statistically
      significant differences were detected in ECG, chest radiography, HRCT, and
      pulmonary function testing between patients with and without PHT. The degree of
      anemia and renal dysfunction, but not the presence of PHT, were the most
      important determinants of plasma (NT-pro)BNP levels. The performed imaging and
      functional studies do not seem to be of value in identifying etiological
      conditions (such as airflow obstruction or parenchymal lung disease) nor do they
      offer clues to the presence of mild PHT in SCD.

PMID- 18819096
TI  - Trisomy 8 in an allogeneic stem cell transplant recipient representative of a
      donor-derived constitutional abnormality.
AB  - Trisomy 8 is a common cytogenetic abnormality in myeloid malignancies. It can
      also be present constitutionally and is associated with a wide range of
      phenotypes. We report a case of a 20-year-old woman with acute myelogenous
      leukemia associated with the 11q23/MLL translocation who underwent allogeneic
      hematopoietic stem cell transplantation (HSCT) from a healthy, unrelated 26-year
      old female. Cytogenetics on a bone marrow biopsy and aspirate performed 71 days
      after transplant to evaluate pancytopenia identified trisomy 8 in 6 of 7 cells
      examined. The bone marrow was hypocellular but normal by morphology and flow
      cytometry. Fluorescent in situ hybridization (FISH) for the original 11q23/MLL
      translocation was negative. Chimerism analysis using multiplex polymerase chain
      reaction to amplify an informative short tandem repeat demonstrated 97% donor
      cells. These findings were confirmed by repeat bone marrow biopsies at Day 110
      after transplant and 1 year after transplant. With resolution of comorbid
      illness, the patient's peripheral blood counts recovered and remained normal at 1
      year after HSCT. FISH analysis of a cryopreserved sample of the donor graft
      showed trisomy 8 in 120 of 200 cells examined. This represents the first reported
      case of a person with constitutional trisomy 8 mosaicism serving as a stem cell
      donor. The case illustrates the importance of identifying donor-derived
      constitutional abnormalities to avoid the assumption that these cytogenetic
      abnormalities after HSCT are representative of malignant disease.

PMID- 18819097
TI  - The effects of selective breeding for differential rates of 50-kHz ultrasonic
      vocalizations on emotional behavior in rats.
AB  - Fifty-kHz ultrasonic vocalizations have previously been shown to be positively
      correlated with reward and appetitive social behavior in rats, and to reflect a
      positive affective state. In this study, rats selectively bred for high and low
      rates of 50-kHz vocalizations as juveniles were tested as adults in a battery of
      behavioral tests for social/emotional behaviors. We found that animals
      selectively bred for high rates of 50-kHz vocalizations exhibited more crosses
      into the center area of the open field apparatus, were more likely to show a
      preference for a dilute sucrose solution (.8%) compared to tap water, and were
      less aggressive than randomly bred animals. Conversely, animals bred for low
      rates of 50-kHz calls produced more fecal boli during both open field testing and
      "tickling" stimulation, and made less contact with conspecifics in a social
      interaction test compared to randomly bred animals. We also observed that low
      line rats have elevated brain levels of cholecystokinin (CCK) in the cortex,
      which is consistent with literature showing that CCK content in the cortex is
      positively correlated with rates of aversive 22-kHz USVs. Conversely, high line
      animals had elevated levels of met-enkephalin in several brain regions, which is
      consistent with the role of endogenous-opioids in the generation 50-kHz USVs and
      positive affect. These results suggest that animals bred for high rates of 50-kHz
      may show a stress resilient phenotype, whereas low line rats may show a stress
      prone phenotype. As such these animals could provide novel insights into the
      neurobiology of emotion.

PMID- 18819098
TI  - Sphingosine-1-phosphate acts as a developmental stage specific inhibitor of
      platelet-derived growth factor-induced chemotaxis of osteoblasts.
AB  - The development and maintenance of a healthy skeleton depends on the migration of
      cells to areas of new bone formation. Osteoblasts, the bone forming cells of the
      body, mature from mesenchymal stem cells under the influence of bone
      morphogenetic protein. It is unclear at what developmental stage the osteoblasts
      start to migrate to their functional location. We have studied migration of
      immature pre-osteoblasts and of mature osteoblasts in response to Platelet
      derived growth factor (PDGF) and sphingosine-1-phosphate (S1P). PDGF is a growth
      factor involved in bone remodeling and fracture healing whereas S1P is a
      circulating sphingolipid known to control cell trafficking. Our data indicate
      that PDGF acts as a chemotactic cue for pre-osteoblasts. In contrast, S1P is a
      chemorepellent to these cells. Upon Bone Morphogenetic Protein 2-induced
      conversion to the osteoblast phenotype, the chemotaxis response to PDGF is
      retained whereas the sensitivity to S1P is lost. By RNA interference and
      overexpression experiments we showed that the expression level of the S1P2
      receptor is the sole determinant controlling responsiveness to S1P. The combined
      data indicate that migration of osteoblasts is controlled by the balance between
      PDGF, S1P and the differentiation state of the cells. We propose that this
      mechanism preserves the osteoprogenitor pool in the bone marrow, only allowing
      the more differentiated cell to travel to sites of bone formation.

PMID- 18819099
TI  - The accumulation of versican in the nodules of benign prostatic hyperplasia.
AB  - BACKGROUND: Proteoglycans, a complex group of extracellular matrix (ECM)
      molecules, are elevated in benign prostatic hyperplasia (BPH). Versican is a
      stromal proteoglycan present in prostate tissue. Versican expression is elevated
      in tissues with increased proliferation. Based on these observations, we
      determined the extent and distribution of versican expression in prostates with
      BPH. METHODS: The involvement of versican in BPH nodules was compared with levels
      in non-nodular transition (TZ) and peripheral zone (PZ) tissues from 18 human
      prostate glands using immunohistochemistry, Northern blots and/or QRTPCR to
      localize versican and quantify versican mRNA transcript levels, and Western blots
      to assess gene product levels. RESULTS: Increased versican immunoreactivity was
      observed in the stroma of BPH nodules. Higher steady state levels of versican
      variants V0, V1, and V3 mRNA transcript and gene product were detected in the
      nodular tissues than in the non-nodular TZ or PZ parenchyma. CONCLUSIONS: These
      results suggest that versican may play a role in nodule formation in BPH.

PMID- 18819100
TI  - Inflammatory processes of prostate tissue microenvironment drive rat prostate
      carcinogenesis: preventive effects of celecoxib.
AB  - BACKGROUND: Prostate tissue microenvironment is susceptible to several risk
      factors including carcinogens, dietary factors, hormones, cytokines and growth
      factors that could induce chronic inflammation. Because of the difference in the
      serum levels and the intrinsic ability of monocytes/macrophages to cause harm,
      the transcriptional responses triggered by inflammatory stimuli must be
      controlled. Unfortunately, an in-depth association between prostate cancer and
      potential mediators of inflammation has not been completely investigated.
      METHODS: To determine whether activated macrophage (infiltrating monocytes), iNOS
      and NF-kappaB are primary mediators of inflammation, besides COX-2, in prostate
      carcinogenesis, we examined tissue sections of rat prostate tumor induced by N
      methyl-N-nitrosourea (MNU) plus testosterone in a follow-up study. We performed
      H&E and immunohsitochemical staining of the prostate tissue to detect specific
      markers of inflammation. RESULTS: We report an increase in infiltrating monocyte,
      iNOS, NF-kappaBp65, VEGF and TNF-alpha at the early and advanced stages of tumor
      growth in MNU plus testosterone treated rats. Monocyte infiltration was often
      found in the stromal and perivascular regions of the DL prostate. We conclude for
      the first time that prostate cancer induced by MNU plus testosterone partly
      involves mediators of inflammation which could trigger the process of
      carcinogenesis and cause loss of apoptosis. Selective COX-2 inhibitor celecoxib
      at a dose of 500 mg/kg/bw administered for 52 weeks reduced infiltrating
      monocytes, inhibited iNOS, NF-kappaB p65 expression, induced apoptosis and tumor
      growth inhibition. CONCLUSION: Carcinogen plus testosterone induced prostate
      carcinogenesis showing activation of macrophage, iNOS and NF-kappaBp65 could be
      prevented by celecoxib or related anti-inflammatory agents.

PMID- 18819102
TI  - Interleukin-4 activates androgen receptor through CBP/p300.
AB  - BACKGROUND: Aberrant activation of androgen receptor (AR) plays an important role
      in the progression of castration resistant prostate cancer. Interleukin-4 (IL-4)
      enhances AR activation in the absence of androgen and stimulates castration
      resistant growth of androgen-sensitive prostate cancer cells. However, the
      mechanism of IL-4 mediated AR activation has not yet been revealed. METHODS: The
      effect of IL-4 on CBP/p300 expression was examined by Western blot analysis. The
      effect of IL-4 on the interactions of AR and CBP/p300 was examined by co
      immunoprecipitation and ChIP assays. CBP/p300 siRNA was used to knockdown
      CBP/p300 expression to examine the role of CBP/p300 expression on IL-4 mediated
      AR activation. RESULTS: We found that IL-4 increases CBP/p300 protein expression
      and enhances interaction of AR with CBP/p300 proteins through an increase in the
      recruitment of CBP/p300 protein to the androgen responsive elements in the
      promoters of androgen responsive genes. Down regulation of CBP/p300 expression
      using CBP/p300 specific siRNA abolished IL-4 mediated AR activation, suggesting
      that CBP/p300 is responsible for AR activation induced by IL-4. Furthermore, AR
      activation can be enhanced by AR acetylation induced by IL-4 in prostate cancer
      cells. The IL-4 mediated AR acetylation can be blocked by knocking down CBP/p300
      expression using CBP/p300 specific siRNA. CONCLUSION: These results suggest that
      IL-4 activates AR through enhanced expression of CBP/p300 and its histone
      acetyltransferase activity.

PMID- 18819103
TI  - Structural heterogeneity and protein composition of exosome-like vesicles
      (prostasomes) in human semen.
AB  - BACKGROUND: Human seminal fluid contains small exosome-like vesicles called
      prostasomes. Prostasomes have been reported previously to play an important role
      in the process of fertilization by boosting survivability and motility of
      spermatozoa, in addition to modulating acrosomal reactivity. Prostasomes have
      also been reported to present with sizes varying from 50 to 500 nm and to have
      multilayered lipid membranes; however, the fine morphology of prostasomes has
      never been studied in detail. METHODS: Sucrose gradient-purified prostasomes were
      visualized by cryo-electron microscopy (EM). Protein composition was studied by
      trypsin in-gel digestion and liquid chromatography/mass spectrometry. RESULTS:
      Here we report for the first time the detailed structure of seminal prostasomes
      by cryo-EM. There are at least three distinct dominant structural types of
      vesicles present. In parallel with the structural analysis, we have carried out a
      detailed proteomic analysis of prostasomes, which led to the identification of
      440 proteins. This is nearly triple the number of proteins identified to date for
      these unique particles and a number of the proteins identified previously were
      cross-validated in our study. CONCLUSION: From the data reported herein, we
      hypothesize that the structural heterogeneity of the exosome-like particles in
      human semen reflects their functional diversity. Our detailed proteomic analysis
      provided a list of candidate proteins for future structural and functional
      studies.

PMID- 18819104
TI  - Sternocleidomastoid muscle interposition to prevent carotid artery blowout.
AB  - Carotid blow-out syndrome is the most dreaded complication in head and neck
      surgical oncology practice This article describes a simple technique of
      interposition of sternocleidomastoid muscle between pharynx and carotid sheath to
      isolate the latter from salivary contamination in the event of salivary leak.
      Authors have used this technique in 83 laryngectomies with excellent results.

PMID- 18819105
TI  - Use of digitoxin and digoxin as internal standards in HPLC analysis of triterpene
      saponin-containing extracts.
AB  - INTRODUCTION: Saponins are widely distributed complex plant glycosides possessing
      a variety of structure-dependent bioactivities. Quantitation of individual
      saponins is difficult due to lack of available standards, mainly as a consequence
      of purification difficulties. Determination of total saponin content can be
      problematic, often relying on non-specific methods based on butanol solubility,
      haemolytic activity or formation of coloured derivatives. OBJECTIVE: To develop a
      general quantitative method based on the use of the readily available
      cardenolides, digitoxin (1) and digoxin (2), as internal standards in an HPLC-PAD
      based analysis. METHODOLOGY: The cardenolides were run at a variety of
      concentrations to establish linearity and reproducibility of detector response
      and then evaluated as internal standards for quantitation of triterpene saponins
      in several plant-derived extracts by HPLC-PAD. Mixtures of saponins, largely
      freed from other extractables, were obtained by fractionation of total extracts
      on solid phase extraction columns (SPE) employing a water-methanol gradient and
      used for construction of calibration curves. Saponin identification and
      structural information was obtained via a single quadrupole mass detector using
      electrospray ionisation in negative ion mode (ESI(-)). RESULTS: Saponin contents
      in six samples from five species were determined and compared with literature
      results and a gravimetric method based on butanol-water partitioning. Results
      were generally consistent with literature reports and superior to gravimetric
      butanol-water partitioning. CONCLUSION: Digitoxin and digoxin are useful as
      internal standards in HPLC estimation of saponin content. Saponins from different
      species having similar structures and molecular weights afford similar
      calibration curves.

PMID- 18819106
TI  - Brain activity during visual versus kinesthetic imagery: an fMRI study.
AB  - Although there is ample evidence that motor imagery activates similar cerebral
      regions to those solicited during actual movements, it is still unknown whether
      visual (VI) and kinesthetic imagery (KI) recruit comparable or distinct neural
      networks. The present study was thus designed to identify, through functional
      magnetic resonance imaging at 3.0 Tesla in 13 skilled imagers, the cerebral
      structures implicated in VI and KI. Participants were scanned in a perceptual
      control condition and while physically executing or focusing during motor imagery
      on either the visual or kinesthetic components of an explicitly known sequence of
      finger movements. Subjects' imagery abilities were assessed using well
      established psychological, chronometric, and new physiological measures from the
      autonomic nervous system. Compared with the perceptual condition, physical
      executing, VI, and KI resulted in overlapping (albeit non-identical) brain
      activations, including motor-related regions and the inferior and superior
      parietal lobules. By contrast, a divergent pattern of increased activity was
      observed when VI and KI were compared directly: VI activated predominantly the
      occipital regions and the superior parietal lobules, whereas KI yielded more
      activity in motor-associated structures and the inferior parietal lobule. These
      results suggest that VI and KI are mediated through separate neural systems,
      which contribute differently during processes of motor learning and neurological
      rehabilitation.

PMID- 18819107
TI  - Topographic analysis of individual activation patterns in medial frontal cortex
      in schizophrenia.
AB  - Individual variability in the location of neural activations poses a unique
      problem for neuroimaging studies employing group averaging techniques to
      investigate the neural bases of cognitive and emotional functions. This may be
      especially challenging for studies examining patient groups, which often have
      limited sample sizes and increased intersubject variability. In particular,
      medial frontal cortex (MFC) dysfunction is thought to underlie performance
      monitoring dysfunction among patients with schizophrenia, yet previous studies
      using group averaging to compare schizophrenic patients to controls have yielded
      conflicting results. To examine individual activations in MFC associated with two
      aspects of performance monitoring, interference and error processing, functional
      magnetic resonance imaging data were acquired while 17 patients with
      schizophrenia and 21 healthy controls (HCs) performed an event-related version of
      the multisource interference task. Comparisons of averaged data revealed few
      differences between the groups. By contrast, topographic analysis of individual
      activations for errors showed that control subjects exhibited activations
      spanning across both posterior and anterior regions of MFC while patients
      primarily activated posterior MFC, possibly reflecting an impaired emotional
      response to errors in schizophrenia. This discrepancy between topographic and
      group-averaged results may be due to the significant dispersion among individual
      activations, particularly in HCs, highlighting the importance of considering
      intersubject variability when interpreting the medial frontal response to error
      commission.

PMID- 18819108
TI  - Strong resemblance in the amplitude of oscillatory brain activity in monozygotic
      twins is not caused by "trivial" similarities in the composition of the skull.
AB  - Previous twin studies have shown strong heritability of electroencephalogram
      amplitude characteristics, such as power spectra. However, it has been suggested
      that these high heritabilities may reflect "trivial" twin resemblance in
      intervening tissues such as the skull. Here we demonstrate strong monozygotic
      twin correlation (0.79 < r < 0.88) of eyes-closed resting-state
      magnetoencephalogram power, which is insensitive to intervening tissues. These
      results confirm that brain activity itself is highly heritable.

PMID- 18819109
TI  - Hippocampal, amygdala, and neocortical synchronization of theta rhythms is
      related to an immediate recall during rey auditory verbal learning test.
AB  - It is well known that theta rhythms (3-8 Hz) are the fingerprint of hippocampus,
      and that neural activity accompanying encoding of words differs according to
      whether the items are later remembered or forgotten ["subsequent memory effect"
      (SME)]. Here, we tested the hypothesis that temporal synchronization of theta
      rhythms among hippocampus, amygdala, and neocortex is related to immediate
      memorization of repeated words. To address this issue, intracerebral
      electroencephalographic (EEG) activity was recorded in five subjects with drug
      resistant temporal lobe epilepsy (TLE), under presurgical monitoring routine.
      During the recording of the intracerebral EEG activity, the subjects performed a
      computerized version of Rey auditory verbal learning test (RAVLT), a popular test
      for the clinical evaluation of the immediate and delayed memory. They heard the
      same list of 15 common words for five times. Each time, immediately after
      listening the list, the subjects were required to repeat as many words as they
      could recall. Spectral coherence of the intracerebral EEG activity was computed
      in order to assess the temporal synchronization of the theta (about 3-8 Hz)
      rhythms among hippocampus, amygdala, and temporal-occipital neocortex. We found
      that theta coherence values between amygdala and hippocampus, and between
      hippocampus and occipital-temporal cortex, were higher in amplitude during
      successful than unsuccessful immediate recall. A control analysis showed that
      this was true also for a gamma band (40-45 Hz). Furthermore, these theta and
      gamma effects were not observed in an additional (control) subject with drug
      resistant TLE and a wide lesion to hippocampus. In conclusion, a successful
      immediate recall to the RAVLT was associated to the enhancement of temporal
      synchronization of the theta (gamma) rhythms within a cerebral network including
      hippocampus, amygdala, and temporal-occipital neocortex.

PMID- 18819110
TI  - Rapid-resolution liquid chromatography/mass spectrometry for determination and
      quantitation of polyphenols in grape berries.
AB  - A rapid-resolution liquid chromatography/mass spectrometric (RRLC/MS) method for
      detection and quantitation of polyphenols in grape berry skins and seeds has been
      developed. Pulp-free berry skins were treated with liquid nitrogen and ground;
      seeds were also ground. Then, 3 g of samples were extracted with 30 mL of a
      mixture of methanol/water/formic acid 70:30:1 (v/v/v) under sonication and 1
      microL of the final extract was injected into two 100 x 2.1 mm i.d., 1.8 microm
      Zorbax Eclipse plus C18 columns connected in series. Compounds were fractionated
      using a gradient elution of acidified acetonitrile/methanol 50:50 (v/v)/water.
      Columns were thermostatted at 70 degrees C. MS was carried out on an Agilent 6410
      QqQ instrument equipped with an electrospray ionization source. Positive and
      negative MS/MS product ion scans were used for compound identification, whereas
      positive full scan MS in the m/z range 200-1400 was used for quantitation. By
      means of mass spectra comparison, various flavonols, flavan-3-ols, anthocyanins
      and stilbenes were identified. Quantitation was performed by external
      calibration, and concentration values were corrected for matrix effect that was
      evaluated in separate experiments. Semi-quantitative estimation was performed for
      compounds for which standards were not commercially available. Recoveries ranged
      from 90-102% with relative standard deviation (RSD) <5%, whereas the between
      samples RSD was in the range 4-12%. Two surrogate standards were used for quality
      control. The developed method was applied to analyze the polyphenol content of
      three Vitis vinifera table cultivars at physiological maturity and after proper
      preservation for 6 weeks. Results demonstrated that during preservation about
      half of the polyphenol content was lost.

PMID- 18819111
TI  - A gas chromatography/combustion/isotope ratio mass spectrometry system for high
      precision delta13C measurements of atmospheric methane extracted from ice core
      samples.
AB  - Past atmospheric composition can be reconstructed by the analysis of air
      enclosures in polar ice cores which archive ancient air in decadal to centennial
      resolution. Due to the different carbon isotopic signatures of different methane
      sources high-precision measurements of delta13CH4 in ice cores provide clues
      about the global methane cycle in the past. We developed a highly automated
      (continuous-flow) gas chromatography/combustion/isotope ratio mass spectrometry
      (GC/C/IRMS) technique for ice core samples of approximately 200 g. The methane is
      melt-extracted using a purge-and-trap method, then separated from the main air
      constituents, combusted and measured as CO2 by a conventional isotope ratio mass
      spectrometer. One CO2 working standard, one CH4 and two air reference gases are
      used to identify potential sources of isotope fractionation within the entire
      sample preparation process and to enhance the stability, reproducibility and
      accuracy of the measurement. After correction for gravitational fractionation,
      pre-industrial air samples from Greenland ice (1831 +/- 40 years) show a
      delta13C(VPDB) of -49.54 +/- 0.13 per thousand and Antarctic samples (1530 +/- 25
      years) show a delta13C(VPDB) of -48.00 +/- 0.12 per thousand in good agreement
      with published data.

PMID- 18819112
TI  - Structural modifications of serum transthyretin in rats during protein-energy
      malnutrition.
AB  - Transthyretin (TTR) is a sensitive marker of protein-energy malnutrition and
      changes in serum and expression levels during protein and energy deficiency are
      well described. However, little is known about structural modifications of TTR
      during protein and/or energy deprivation. Therefore, the aim of this study was to
      determine the effects of protein inadequacies on post-translational modifications
      of TTR. For this purpose, male Wistar rats were fed a diet with either casein or
      gelatine as sole protein source subsequent to a protein wash-out period. Changes
      in TTR serum levels as well as other markers of nutritional status as body
      weight, food consumption, total serum protein and serum RBP4 levels as well as
      antioxidative capacity were determined. Post-translational modifications of TTR
      were examined by matrix-assisted laser desorption/ionisation time-of-flight mass
      spectrometry (MALDI-TOFMS) analysis. The rats from the gelatine group revealed a
      marked change in the post-translational modification pattern of TTR which was
      reflected by a significant elevation of sulfonated TTR and which was inversely
      correlated to the antioxidative capacity. Additionally, the elevation of
      sulfonated TTR was accompanied by a decrease in body weight and food consumption,
      low antioxidative capacity as well as a deprivation of serum TTR, RBP4 and total
      serum protein levels in the animals of the gelatine group. Protein-energy
      malnutrition leads therefore next to changes in TTR serum concentration, also to
      changes in the post-translational modification pattern of TTR. Such changes are
      probably induced by protein-energy malnutrition-driven oxidative stress and might
      be linked to alterations in protein function and stability.

PMID- 18819113
TI  - Development and validation of an analytical method for the simultaneous
      determination of cocaine and its main metabolite, benzoylecgonine, in human hair
      by gas chromatography/mass spectrometry.
AB  - A new, simple and rapid procedure has been developed and validated for the
      determination of cocaine and its main metabolite, benzoylecgonine, in human hair
      samples. After extraction from within the hair matrix by a mixture of
      methanol/hydrochloric acid (2:1) at 65 degrees C for 3 h, and sample cleanup by
      mixed-mode solid-phase extraction (SPE), the extracts were analyzed by gas
      chromatography/mass spectrometry (GC/MS), after derivatization with N-methyl-N
      (trimethylsilyl)trifluoroacetamide with 5% chlorotrimethylsilane. Using a sample
      size of only 20 mg of hair, limits of detection (LODs) and quantitation (LOQs)
      were, respectively, 20 and 50 pg/mg for cocaine, and 15 and 50 pg/mg for
      benzoylecgonine, achieving the cut-off values proposed by the Society of Hair
      Testing for the analysis of these compounds in hair. The method was found to be
      linear (weighing factor of 1/x) between the LOQ and 20 ng/mg for both compounds,
      with correlation coefficients ranging from 0.9974 to 0.9996 for cocaine; and from
      0.9981 to 0.9994 for benzoylecgonine. Intra- and interday precision and accuracy
      were in conformity with the criteria normally accepted in bioanalytical method
      validation. The sample cleanup step presented a mean absolute recovery greater
      than 90% for both compounds. The developed method may be useful in forensic
      toxicology laboratories for the analysis of cocaine and benzoylecgonine in hair
      samples, taking into account its speed (only 3 h are required for the extraction
      of the analytes from within the matrix, whereas 5 h or even overnight extractions
      have been reported) and the low limits achieved (using a single quadrupole mass
      spectrometer, which is available in most laboratories).

PMID- 18819114
TI  - Gas-phase peptide fragmentation: how understanding the fundamentals provides a
      springboard to developing new chemistry and novel proteomic tools.
AB  - This tutorial provides an overview of the evolution of some of the key concepts
      in the gas-phase fragmentation of different classes of peptide ions under various
      conditions [e.g. collision-induced dissociation (CID) and electron transfer
      dissociation (ETD)], and then demonstrates how these concepts can be used to
      develop new methods. For example, an understanding of the role of the mobile
      proton and neighboring group interactions in the fragmentation reactions of
      protonated peptides has led to the design of the 'SELECT' method. For ETD, a
      model based on the Landau-Zener theory reveals the role of both thermodynamic and
      geometric effects in the electron transfer from polyatomic reagent anions to
      multiply protonated peptides, and this predictive model has facilitated the
      design of a new strategy to form ETD reagent anions from precursors generated via
      ESI. Finally, two promising, emerging areas of gas-phase ion chemistry of
      peptides are also described: (1) the design of new gas-phase radical chemistry to
      probe peptide structure, and (2) selective cleavage of disulfide bonds of
      peptides in the gas phase via various physicochemical approaches.

PMID- 18819116
TI  - Inappropriate stents: primary cause of failure of stent redilation in coarctation
      of the aorta.

PMID- 18819117
TI  - Transcatheter aortic valve replacement malposition and embolization: innovation
      brings solutions also new challenges.

PMID- 18819118
TI  - Bayesian fitting of a logistic dose-response curve with numerically derived
      priors.
AB  - In this report we describe the Bayesian analysis of a logistic dose-response
      curve in a Phase I study, and we present two simple and intuitive numerical
      approaches to construction of prior probability distributions for the model
      parameters. We combine these priors with the expert prior opinion and compare the
      results of the analyses with those obtained from the use of alternative prior
      formulations.

PMID- 18819119
TI  - A high-resolution scanning microprobe matrix-assisted laser desorption/ionization
      ion source for imaging analysis on an ion trap/Fourier transform ion cyclotron
      resonance mass spectrometer.
AB  - A new scanning microprobe matrix-assisted laser desorption/ionization (SMALDI)
      ion source for high spatial resolution has been developed for linear ion trap and
      Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS). The
      source is fully compatible with commercial ion trap flanges (such as the LTQ
      series, Thermo Fisher Scientific). The source is designed for atmospheric
      pressure (AP) operation but is also suitable for mid-pressure operation. The AP
      mode is especially useful for investigating volatile compounds. The source can be
      interchanged with other ion sources within a minute when operated in the AP mode.
      Combining high-lateral resolution MALDI imaging with high mass resolution and
      high mass accuracy mass spectrometry, available in the FT-ICR mode, provides a
      new quality of analytical information, e.g. from biological samples. First
      results obtained with the new ion source demonstrate a maximum lateral resolution
      of 0.6 by 0.5 microm. Depending on the limit of detection of the chosen mass
      analyzer, however, the size of the focus had to be enlarged to a diameter of up
      to 8 microm in the FT-ICR mode, in order to create enough ions for detection.
      Mass spectra acquired for analytical imaging were obtained from single laser
      pulses per pixel in all the experiments. This mode allows us to investigate
      biological thin sections with desorption focus diameters in the micrometer range,
      known to cause complete evaporation of material under the laser focus with a very
      limited number of laser pulses. As a first example, peptide samples deposited in
      microstructures were investigated with the new setup. A high quality and validity
      of the acquired images were obtained in the ion trap mode due to the low limit of
      detection. High mass resolution and accuracy but poorer image quality were
      obtained in the ICR mode due to the lower detection sensitivity of the ICR
      detector.

PMID- 18819120
TI  - Prevention and management of transcatheter balloon-expandable aortic valve
      malposition.
AB  - OBJECTIVES: Early clinical outcomes in selected high-risk patients undergoing
      catheter-based aortic valve replacement (AVR) compare favorably with conventional
      surgical AVR. Improved understanding of the mechanisms of success and failure of
      transcatheter AVR will likely improve outcomes further. To this end, we examined
      our experience during the developmental phases of transcatheter AVR and describe
      the causes and management of prosthetic valve malposition. METHODS: Transcatheter
      balloon-expandable AVR was performed in 170 patients at two centers. Malposition
      was defined as prosthetic valve implantation in a location other than within the
      native valve. Patients were prospectively identified and followed as part of an
      ongoing database. RESULTS: Valve malposition occurred in 9 of 170 patients
      (5.3%). Final position was supravalvular in eight of nine cases. In all cases,
      embolization to the ascending aorta occurred within a few cardiac cycles
      following deployment. Importantly, late embolization was not observed. In most
      cases, the prosthesis was uneventfully repositioned in the more distal aorta.
      Positioning was subvalvular in one patient (0.6%), resulting in a severe
      regurgitation with residual native valve stenosis. Implantation of a second
      transcatheter valve was attempted in six patients and was successful in all.
      Conventional AVR was performed in two patients, with early mortality in one. At
      late follow-up (mean 412 days), seven of nine patients remain alive (78%) with a
      functioning prosthesis and relief of aortic stenosis. CONCLUSIONS: Malposition of
      current balloon-expandable aortic valves is a largely preventable complication.
      An improved understanding of the procedure will likely minimize this possibility
      and mitigate the consequences should malposition occur.

PMID- 18819121
TI  - Percutaneous rescue of left ventricular embolized amplatzer septal occluder
      device.
AB  - Transcatheter atrial septal defect (ASD) closure has proven to be safe and
      effective, and it is rapidly becoming the standard treatment for secundum-type
      ASDs. However, device embolization occurs in about 0.55% of cases, regardless of
      ASD and device size and/or physician's expertise. Percutaneous retrieval of the
      embolized device is possible in about 50% of cases, and several techniques have
      been described, including the use of large sheaths, gooseneck snares, or
      bioptomes. This is the first successful and reported case of retrieval of an
      embolized amplatzer septal occluder (ASO) from the left ventricle that was
      achieved by using a modified snare technique. This was done after an unsuccessful
      attempt at retrieval with a bioptome that led to a never previously reported
      complication. Of the 32 reported cases of ASO embolization, percutaneous
      retrieval was successful in 16 cases (50%) and none were obtained following left
      ventricular embolization. Even in experienced hands, the observed rate of
      embolization when using an ASO device is not negligible. Percutaneous retrieval
      is also possible from the left ventricle but in some cases nonstandardized
      devices and strategies may be required.

PMID- 18819122
TI  - Health-related quality of life, cognitive functioning and behaviour problems in
      children with Langerhans cell histiocytosis.
AB  - BACKGROUND: This study was designed to evaluate generic and disease-specific
      health-related quality of life (HRQoL), cognitive functioning and behaviour
      problems of children with Langerhans Cell Histiocytosis (LCH). Furthermore, we
      investigated which medical determinants and social demographic factors were
      predictive for HRQoL, cognitive functioning and behavioural problems. PROCEDURE:
      In this cross-sectional case-control study 24 children ranging from 7 to 17 years
      of age were administered a HRQoL questionnaire, cognitive tests and behaviour
      ratings. In addition, a disease-specific HRQoL measure was developed and tested.
      Results were compared to a reference group consisting of healthy peers and to
      proxy-ratings by parents and teachers. RESULTS: Children with LCH reported a
      lower physical HRQoL than the reference group (P <or= 0.05). Children older than
      12 reported lower HRQoL scores. Scores on the disease-specific HRQoL
      questionnaire were lower than on the generic measure used. Performances on
      cognitive tests varied widely, short term visual memory was most affected. Twenty
      five percent of the children follow special education. According to parents and
      teachers, children with LCH had more internalising behaviour problems (i.e.,
      anxiety and depression), compared to the instrument norms. Children with Diabetes
      Insipidus, other CNS involvement and children who have had chemotherapy had more
      cognitive and behaviour problems than the other children with LCH. CONCLUSIONS:
      HRQoL is affected in children with LCH, especially in older children. Children
      with LCH show more internalising problem behaviour than their peers. Teachers are
      important additional informants about behaviour problems.

PMID- 18819123
TI  - High risk neuroblastoma: a persistent therapeutic challenge.

PMID- 18819124
TI  - Bivalirudin for anticoagulation in children.
AB  - BACKGROUND: Thromboembolism in children is typically treated with unfractionated
      heparin (UH) or low molecular weight heparin (LMWH). Both rely on antithrombin
      (AT) for their action. In addition, heparin-induced thrombocytopenia (HIT) is a
      potentially serious complication of heparin use in children. Bivalirudin or other
      direct thrombin inhibitors may be a useful alternative to heparins in treating
      thrombosis in children. PROCEDURE: We report a retrospective review to assess the
      efficacy and safety of bivalirudin in pediatric patients with thrombosis.
      RESULTS: Sixteen children received bivalirudin for thrombosis or prevention of
      thrombosis at the Children's Hospital of Illinois from January 2005 to January
      2007. Patients received a bolus dose of 0.25 mg/kg followed by a continuous
      infusion (0.16 +/- 0.07 mg kg(-1) hr(-1)) titrated to 1.5-2.5 times the baseline
      activated partial thromboplastin time (aPTT). Positive correlation between the
      bivalirudin average infusion rate and aPTT was observed in twelve patients.
      Ultrasonographic evidence of thrombus regression was noted at 72 hr in 10 of 10
      patients. One patient experienced hematuria after catheterization of the urethra.
      CONCLUSION: Bivalirudin was effective and well-tolerated in these patients.
      Further studies should be conducted to better define safety and efficacy of
      bivalirudin in pediatric patients.

PMID- 18819125
TI  - Impurity analysis of pharmaceuticals using capillary electromigration methods.
AB  - This review deals with the determination of impurities in pharmaceuticals by
      electromigration methods in the capillary format. These separation methods are
      either based on the different effective mobility of the charged analytes (as in
      zone electrophoresis and isotachophoresis) or include hybrid methods such as
      micellar electrokinetic chromatography, microemulsion electrokinetic
      chromatography and electrochromatography. The pharmaceutically active compounds
      under consideration belong to chemotherapeutic agents, central nervous system
      drugs, histamine receptor drugs, cardiovascular drugs, anticancer drugs, anti
      inflammatory drugs and some other drugs. The review discusses about 150
      publications from the period between 1980 and 2007 with special emphasis on the
      recent trends and gives details about the experimental conditions applied for
      analyses and the obtained analytical performance parameters.

PMID- 18819126
TI  - Lack of early bevacizumab-related skeletal radiographic changes in children with
      neuroblastoma.

PMID- 18819127
TI  - Sentinel node biopsy in pediatric soft tissue sarcomas of extremities.
AB  - BACKGROUND: Sentinel Node Biopsy is an established staging technique in many
      adult malignancies. However, only few reports describe this procedure for the
      evaluation of regional lymph nodes in childhood and adolescents. Our experience
      with sentinel node biopsy in soft tissue sarcomas of extremities in children is
      reported. METHODS: Seventeen children were evaluated with sentinel node biopsy
      between 2002 and 2007: 11 at initial surgery, 5 at primary re-excision, 1 at
      local relapse. The diagnosis was rhabdomyosarcoma in 5 and other soft tissue
      sarcomas in 12: Ewing/PNET sarcoma 6, epithelioid sarcoma 1, malignant peripheral
      nerve-sheath tumor 1, undifferentiated sarcoma 1, myxoid liposarcoma 2, adult
      type fibrosarcoma 1. Primary sites included lower limbs (8), upper limbs (9).
      Mapping of nodes was performed with lymphoscintigraphy plus intra-operative
      injections with blue-dye in 14 cases, with lymphoscintigraphy and intra-operative
      injections alone in 2 and 1, respectively. RESULTS: Of the 17 lymphatic regions
      (9 axilla, 8 inguinal), 16 were identified with lymphoscintigraphy, 15 by intra
      operative injections. Thirty-five lymph nodes were removed. Nodes were positive
      for metastasis in two patients with alveolar rhabdomyosarcoma and
      undifferentiated sarcoma. There were no complications. No further lymph node
      metastases were recognized either at diagnosis or during the follow-up (6-78
      months). CONCLUSIONS: Sentinel node biopsy was technically feasible, reliable,
      and free of complications. It could be an alternative to aggressive or random
      biopsies for extremity rhabdomyosarcoma and it can contribute to define those non
      rhabdomyosarcoma soft tissue sarcomas that spread to regional nodes.

PMID- 18819128
TI  - Pre- and post-natal treatment of hemophagocytic lymphohistiocytosis.
AB  - Hemophagocytic lymphohistiocytosis (HLH) is a rare autosomal recessive disorder
      of infancy and childhood that is invariably fatal if not treated. We report on
      the first patient to receive post-natal HSCT for HLH after receiving in utero
      chemotherapy for disease stabilization.

PMID- 18819129
TI  - Effect of childhood cancer treatment on fertility markers in adult male long-term
      survivors.
AB  - BACKGROUND: Although it is accepted that pediatric cancer treatment harbors a
      risk of gonadal damage, large cohort studies using up-to-date fertility markers
      are lacking. PROCEDURE: The aim of our study was to evaluate the gonadal toxicity
      of childhood cancer treatment using fertility markers. We included 248 adult male
      long-term survivors of childhood cancer. Median age at diagnosis: 5 years, median
      age at follow-up: 24 years, median follow-up time 18 years. We evaluated patient
      characteristics, treatment modalities, testicular size, and endocrinological
      parameters including Inhibin B, luteinizing hormone (LH), follicle-stimulating
      hormone (FSH), and testosterone. RESULTS: The median value of Inhibin B in the
      cancer survivor group was 126 ng/L versus 177 ng/L in the control group (P <
      0.001). In the survivors, 67% had Inhibin B levels below the normal reference
      value of 150 ng/L compared with 26% in the control group (P < 0.05). Inhibin B
      was the most sensitive discriminator between survivors and controls.
      Significantly decreased Inhibin B levels and increased FSH levels were found in
      men treated for Hodgkin and non-Hodgkin lymphoma, acute-myeloid leukemia,
      neuroblastoma, and sarcoma as compared to other malignancies. Cumulative dosages
      of procarbazine and cyclophosphamide were the only independent chemotherapy
      related predictors for decrease of Inhibin B levels and increase of FSH. Age at
      time of treatment did not influence post-treatment Inhibin B or FSH levels.
      CONCLUSIONS: Severe gonadal impairment is a risk in a considerable subgroup of
      childhood cancer survivors based on current fertility markers like Inhibin B.
      Males receiving gonadotoxic treatment before puberty are not protected from post
      treatment gonadal dysfunction.

PMID- 18819130
TI  - Lipid-gold-nanoparticle hybrid-based gene delivery.

PMID- 18819131
TI  - Polymer-assisted generation of antimony-doped SnO2 nanoparticles with high
      crystallinity for application in gas sensors.

PMID- 18819132
TI  - A polydiacetylene microchip based on a biotin-streptavidin interaction for the
      diagnosis of pathogen infections.
AB  - A micropatterned polydiacetylene (PDA) chip, utilizing the unique fluorogenic
      property of PDA and a specific biotin-streptavidin (STA) interaction, is
      constructed to detect pathogen infections. To construct the PDA chip, biotin
      modified diacetylene liposomes are immobilized on aldehyde glass and conjugated
      with STA, followed by UV irradiation to polymerize the STA-functionalized
      diacetylene liposomes. Genomic DNA of a model pathogen, Chlamydia trachomatis, is
      isolated from human samples and biotin-labeled target DNA is obtained through PCR
      amplification using biotin-11-dUTP. Owing to the stimulus caused by the biotin
      STA interaction, the biotinylated DNA induces an intense fluorescence signal on
      the immobilized PDA. By using this strategy, it is possible to diagnose Chlamydia
      infections by applying DNA samples from several nonhealthy humans to a single PDA
      chip. The results of this study serve as the basis for a new strategy for
      fluorogenic PDA microarray-based diagnosis of pathogen infections.

PMID- 18819133
TI  - Epitaxial integration of nanowires in microsystems by local micrometer-scale
      vapor-phase epitaxy.
AB  - Free-standing epitaxially grown nanowires provide a controlled growth system and
      an optimal interface to the underlying substrate for advanced optical,
      electrical, and mechanical nanowire device connections. Nanowires can be grown by
      vapor-phase epitaxy (VPE) methods such as chemical vapor deposition (CVD) or
      metal organic VPE (MOVPE). However, VPE of semiconducting nanowires is not
      compatible with several microfabrication processes due to the high synthesis
      temperatures and issues such as cross-contamination interfering with the intended
      microsystem or the VPE process. By selectively heating a small microfabricated
      heater, growth of nanowires can be achieved locally without heating the entire
      microsystem, thereby reducing the compatibility problems. The first demonstration
      of epitaxial growth of silicon nanowires by this method is presented and shows
      that the microsystem can be used for rapid optimization of VPE conditions. The
      important issue of the cross-contamination of other parts of the microsystem
      caused by the local growth of nanowires is also investigated by growth of GaN
      near previously grown silicon nanowires. The design of the cantilever heaters
      makes it possible to study the grown nanowires with a transmission electron
      microscope without sample preparation.

PMID- 18819134
TI  - Carbon-nanotube-resonator-based biosensors.

PMID- 18819135
TI  - Core/shell biocomposites from the hierarchical assembly of bionanoparticles and
      polymer.

PMID- 18819136
TI  - Plasmon hybridization in stacked double gold nanorings with reduced symmetry.

PMID- 18819137
TI  - Environmentally responsive core/shell particles via electrohydrodynamic co
      jetting of fully miscible polymer solutions.
AB  - Herein it is demonstrated that electrohydrodynamic co-jetting is not limited to
      Janus-type particles, but can also be used for the preparation of core/shell
      particles. Using side-by-side flow of miscible polymer solutions,
      electrohydrodynamic co-jetting offers an elegant and scalable route towards
      preparation of core/shell particles with otherwise difficult-to-prepare particle
      architectures, including particles with hydrophilic shell and core. Throughout
      this study, electrohydrodynamic co-jetting of aqueous solutions consisting of a
      mixture of PAAm-co-AA and PAA is used, and a range of different types of
      particles with distinct compartments are observed. Transition from Janus
      particles to core/shell particles appears to be caused by changes in the relative
      conductivity of the two jetting solutions. After crosslinking, the core/shell
      particles are stable in aqueous solution and exhibit reproducible swelling
      behavior while maintaining the original core/shell geometry. In addition, the pH
      responsiveness of the particles is demonstrated by repeatedly switching the
      environmental pH between 1.3 and 12. Moreover, the core/shell particles show
      surprising uptake selectivity. For instance, a 450% increase in uptake of 6
      carboxyfluorescein over rhodamine B base is found.

PMID- 18819138
TI  - Nanopore analysis of the folding of zinc fingers.

PMID- 18819139
TI  - Formation of bubbles and droplets in parallel, coupled flow-focusing geometries.
AB  - This paper describes the mechanism of formation of bubbles of nitrogen in water
      containing Tween 20 as a surfactant, and of droplets of water in hexadecane
      containing Span 80 as a surfactant. The study of these microfluidic systems
      compares two or four flow-focusing generators coupled through shared inlets,
      supplying the continuous phase, and through a common outlet channel. The
      processes that form bubbles in neighboring generators interact for a wide range
      of flow parameters; the formation of bubbles alternates in time and space, and
      the bubbles assemble into complex patterns in the outlet channel. The dynamics of
      formation of bubbles in these systems are stable for long time (at least 10 min).
      For a certain range of flow parameters, the coupled flow-focusing generators
      exhibit two stable modes of operation for a single set of flow parameters. The
      dynamics of formation of droplets of water in hexadecane by the coupled flow
      focusing generators are simpler--the adjacent generators produce only
      monodisperse droplets over the entire range of flow parameters that are explored.
      These observations suggest that the mechanism of interaction between coupled flow
      focusing generators relies on the compressibility of the dispersed phase (e.g.,
      the gas or liquid), and on variations in pressure at the flow-focusing orifices
      induced by the breakup of bubbles or droplets.

PMID- 18819140
TI  - A novel flow-cytometry-based assay for cellular uptake studies of polyelectrolyte
      microcapsules.
AB  - A flow-cytometry-based assay is presented with which the uptake of
      polyelectrolyte capsules can be quantified. The cavity of the capsules is loaded
      with the pH-sensitive dye SNARF, which emits in the red and green in alkaline and
      acidic environments, respectively. By recording the fluorescence intensities in
      the red and green channels, the localization of capsules associated with cells
      can be determined. Capsules adherent to the outer cell membrane fluoresce in the
      red due to the alkaline pH of the cell medium, whereas capsules internalized by
      cells fluoresce in the green due to the acidic pH in the
      endosomal/lysosomal/phagosomal compartments in which incorporated capsules are
      located. Adding the SNARF readout to the scattering signal typically derived with
      flow cytometry analysis allows for a more detailed quantitative analysis of
      particle uptake, which can also distinguish between adherent and ingested
      particles.

PMID- 18819141
TI  - Bulk electroluminescence from conjugated polymer thin films via the formation of
      gold nanoislands.

PMID- 18819142
TI  - Direct high-performance liquid chromatographic separation of the enantiomers of
      venlafaxine and 11 analogs using amylose-derived chiral stationary phases.
AB  - A direct liquid chromatographic enantioselective separation of venlafaxine and 11
      analogs was obtained in the normal phase mode using Chiralpak AD. For some
      compounds, a comparison between the enantioseparation using coated and
      immobilized amylose tris(3,5-dimethylphenylcarbamate) chiral stationary phases
      (Chiralpak AD and Chiralpak IA, respectively) was made. The best separations were
      achieved on Chiralpak AD with ethanol as alcoholic modifier in a mobile phase
      made basic by DEA addition: separation factor ranges between 2.08 and 1.15 and
      resolution factor between 7.0 and 1.0. Using the same CSP and 2-propanol doped
      with TFA as acidic modifier, 10 compounds were enantioseparated with separation
      factor ranging between 1.40 and 1.04 and resolution factor between 3.1 and 0.3.
      The use of ethanol as alcoholic modifier also has the advantage of better
      solubility of the compounds in the mobile phase. The nature of the substituent
      (electron donating or withdrawing) affects in general the separation factor. A
      memory effect that involves a long equilibration time of the CSP is present when
      switching from an acidic mobile phase to a basic one.

PMID- 18819143
TI  - "Neither horseshoes nor hand grenades"--does close count in percutaneous coronary
      revascularization?

PMID- 18819144
TI  - Repetita iuvant.

PMID- 18819145
TI  - Image guidance for PFO closure: is transnasal TEE an option?

PMID- 18819146
TI  - Results of the U.S. ARRIVE 1 registry: 2-year outcomes.

PMID- 18819147
TI  - Is the coronary physiology of bypass grafts different from that of the native
      coronary artery? Comment on the "Hemodynamic evaluation of coronary artery bypass
      graft lesions using fractional flow reserve".

PMID- 18819148
TI  - Myocardial protection with a beta blocker and glycoprotein IIb/IIIa inhibitor
      during PCI: attractive concept, but limited evidence of benefit.

PMID- 18819149
TI  - Vascular occlusion after vascular closure: rare but not rare enough.

PMID- 18819150
TI  - Intermittent oral trimethoprim/sulfamethoxazole on two non-consecutive days per
      week is effective as Pneumocystis jiroveci pneumonia prophylaxis in pediatric
      patients receiving chemotherapy or hematopoietic stem cell transplantation.
AB  - Pneumocystis jiroveci pneumonia (PCP) is a serious complication in patients
      receiving chemotherapy or hematopoietic stem cell transplantation. Current
      recommendations for trimethoprim-sulfamethoxazole (TMP-SMZ) dosing as PCP
      prophylaxis in immunocompromised patients are based on either daily dosing or
      dosing three consecutive days per week. We report our experience of prophylaxis
      with TMP-SMZ twice daily on two non-consecutive days per week in 145
      immunocompromised children with hematologic disorders, cancer, or metabolic
      disorders following chemotherapy or hematopoietic stem cell transplantation.
      There were no breakthrough cases of PCP. We therefore conclude our prophylaxis
      regimen is effective against PCP in immunocompromised children.

PMID- 18819151
TI  - Treatment of peritoneal mesothelioma in pediatric patients.
AB  - Peritoneal mesothelioma is a rare and often aggressive malignancy, mostly
      affecting asbestos exposed adults. We present four pediatric peritoneal cases
      treated with a cisplatin-based doublet regimen, the standard of care in the
      systemic therapy of adult mesothelioma. Treatment was well tolerated, and three
      of these patients have achieved long-term survival. The fathers of three of the
      patients worked in the construction industry and may have been the source of
      indirect asbestos exposure.

PMID- 18819152
TI  - Type II autosomal recessive cutis laxa: report of another patient and molecular
      studies concerning three candidate genes.
AB  - Cutis laxa is a rare disorder of connective tissue in which the skin sags
      excessively, giving the individual an aged appearance. In the present study we
      analyzed three unrelated families with type II autosomal recessive cutis laxa for
      mutations in three genes implicated in other forms of cutis laxa; LOX, FBLN4, and
      FBLN5 genes. Two individuals have been previously reported, and the third case is
      described in detail. No causative mutations were identified.

PMID- 18819153
TI  - Radiation-induced peripheral artery disease.
AB  - Radiation therapy is a cause of cardiovascular morbidity and mortality. This is
      due to the significant degree of atherosclerosis seen in the vessels in the
      vicinity of the area being irradiated. Radiation-induced peripheral arterial
      disease is increasingly being recognized as large populations of cancer patients
      survive longer, yet it is a problem that is often under reported. Although it has
      most commonly been associated with carotid artery disease, all vascular beds are
      prone to this form of injury. The injury is accelerated by usual risk factors for
      atherosclerosis. Developing a healthy lifestyle, dietary prudence and the
      aggressive treatment of hypertension, diabetes mellitus, and dyslipidemia should
      all be encouraged in this patient population. When revascularization strategies
      are warranted, the percutaneous approach may be superior to open surgery as
      technical difficulties may arise in the fibrotic, scarred tissue. Stenting with
      distal embolic protection devices should be considered as the treatment of choice
      for patients with radiation-induced carotid artery disease. Several reports also
      suggest good results with balloon angioplasty with or without stenting in the
      case of radiation-induced renal, iliac, and femoral artery disease. Lifelong
      antiplatelet therapy may be appropriate.

PMID- 18819154
TI  - The "criminalization" of off-label device use.

PMID- 18819155
TI  - Starch and albumin mixture as replacement fluid in therapeutic plasma exchange is
      safe and effective.
AB  - Therapeutic plasma exchange (TPE) is an effective treatment in Myasthenia gravis
      (MG) and Guillain-Barre syndrome (GBS) and 5% human albumin is the replacement
      fluid of choice; however, it is expensive. More recently, it has been suggested
      that starch is a safe and cheaper choice to human albumin. OBJECTIVE: To evaluate
      our 5-year experience using 3% hydroxyethyl starch (HES) and 5% human albumin
      mixture, as replacement fluid in TPE for these diseases. MATERIALS AND METHODS:
      Retrospective study carried out from January 2001 through September 2006. We
      included those patients with MG and GBS undergoing TPE. We analyzed clinical
      outcome (CO) and adverse events (AE) and our results were compared with a
      previous study which included similar patients undergoing TPE using just 5% human
      albumin. RESULTS: Thirty-one procedures were carried out in 26 patients, a total
      of 147 TPE sessions. In the group of MG we had 57% complete responses (CR) and
      86% overall response (OR) while in the group of GBS we had 40% CR and 60% OR.
      When we analyzed our CO with the previous study no statistical differences were
      found. Mean processed plasma volume (PPV) was 4.2 in MG and 5.5 in GBS. Twenty
      patients had AE, being hypotension and catheter dysfunction the most frequent
      ones, while tachycardia, hypertension and paresthesias were statistically more
      frequent in the HES/albumin group. CONCLUSIONS: TPE with a mixture of 3% HES and
      5% human albumin is as effective and safe as 5% human albumin alone for patients
      with these diseases.

PMID- 18819156
TI  - Manufacture of stable palladium and gold nanoparticles on native and genetically
      engineered flagella scaffolds.
AB  - The use of bacterial flagella as templates for the immobilization of Pd and Au
      nanoparticles is described. Complete coverage of D. desulfuricans flagellar
      filaments by Pd(0) nanoparticles was obtained via the H(2)-mediated reduction of
      Pd(NH3)4]Cl2 but similar results were not obtained using HAuCl4. The introduction
      of additional cysteine-derived thiol residues in the E. coli FliC protein
      increased Au(III) sorption and reduction onto the surface of the flagellar
      filament and resulted in the production of stabilized Au(0) nanoparticles of
      approximately 20-50 nm diameter. We demonstrate the application of molecular
      engineering techniques to manufacture biologically passivated Au(0) nanoparticles
      of a size suitable for catalytic applications.

PMID- 18819157
TI  - A model of Agrobacterium tumefaciens vacuum infiltration into harvested leaf
      tissue and subsequent in planta transgene transient expression.
AB  - Agrobacterium-mediated gene transfer, or agroinfiltration, can be a highly
      efficient method for transforming and inducing transient transgene expression in
      plant tissue. The technique uses the innate DNA secretion pathway of
      Agrobacterium tumefaciens to vector a particular plasmid-encoded segment of DNA
      from the bacteria to plant cells. Vacuum is often applied to plant tissue
      submerged in a suspension of A. tumefaciens to improve agroinfiltration. However,
      the effects of vacuum application on agroinfiltration and in planta transient
      transgene expression have not been well quantified. Here we show that vacuum
      application and release act to drive A. tumefaciens suspension into the interior
      of leaf tissue. Moreover, the amount of suspension that enters leaves can be
      predicted based on the vacuum intensity and duration. Furthermore, we show that
      transient expression levels of an agroinfiltrated reporter gene vary in response
      to the amount of A. tumefaciens vacuum infiltrated into leaf tissue, suggesting
      that vacuum infiltration conditions can be tailored to achieve optimal transient
      transgene expression levels after agroinfiltration.

PMID- 18819158
TI  - Rational management of endocrine resistance in breast cancer: a comprehensive
      review of estrogen receptor biology, treatment options, and future directions.
AB  - Endocrine therapy for breast cancer was introduced more than 100 years ago. In
      the last 30 years, it has been demonstrated that tamoxifen significantly improves
      outcomes for patients with hormone-responsive breast tumors. Aromatase
      inhibitors, which suppress the production of estrogen, are recognized today as an
      effective alternative for estrogen-receptor-positive breast cancer in
      postmenopausal women. However, despite an initial response to treatment, many
      tumors eventually recur or progress. When selecting subsequent endocrine therapy,
      it is helpful to understand the mechanisms of hormone resistance, consider the
      goals of treatment, and evaluate the clinical potential of each available drug.
      The objective of this article was to review the underlying mechanisms of action
      and resistance for each type of hormone therapy, evaluate the most recent data
      regarding the use of endocrine agents after disease progression or recurrence,
      and explore potential combinations of hormone therapies with novel molecules that
      target key growth factor signaling pathways.

PMID- 18819159
TI  - Dyslexic participants show intact spontaneous categorization processes.
AB  - We examine the performance of dyslexic participants on an unsupervised
      categorization task against that of matched non-dyslexic control participants.
      Unsupervised categorization is a cognitive process critical for conceptual
      development. Existing research in dyslexia has emphasized perceptual tasks and
      supervised categorization tasks (for which intact attentional processes are
      paramount), but there have been no studies on unsupervised categorization. Our
      investigation was based on Pothos and Chater's (Cognit. Sci., 2002; 26: 303-343)
      model of unsupervised categorization and the corresponding methodology for
      analysing results. Across all performance indices and various data-processing
      options, we could identify no difference between dyslexic and non-dyslexic
      participants.

PMID- 18819161
TI  - Intravascular large B-cell lymphoma with FDG accumulation in the lung lacking
      CT/(67)gallium scintigraphy abnormality.
AB  - Intravascular large B-cell lymphoma (IVLBCL) is a rare lymphoma characterized by
      the presence of large tumour cells within the blood vessels. It has been
      considered that IVLBCL is a highly malignant disease with poor prognosis.
      However, it has been shown that a therapeutic effect resembling that of
      conventional B-cell lymphomas may be obtained with the application of systemic
      chemotherapy at the early stage of this disease. Although involvement in the lung
      is often detected at autopsy, early diagnosis is quite difficult. In this report,
      we present a case of IVLBCL with pulmonary involvement where 18-fluoro
      deoxyglucose positron emission tomography (FDG-PET) was useful in the early
      diagnosis. Neither computed tomography (CT) nor (67)gallium scintigraphy could
      reveal the presence of disease in the lung. Histological evidence of IVLBCL was
      obtained by TBLB after FDG uptake in the lung was confirmed by FDG-PET. The
      patient exhibited a good response to the subsequent combination chemotherapy. We
      propose that FDG-PET is a powerful tool for the early diagnosis of IVLBCL with
      pulmonary involvement, if the possibility of this disease presents in the patient
      with respiratory symptoms without abnormal findings by CT and (67)gallium
      scintigraphy.

PMID- 18819162
TI  - Prefrontal brain morphology and executive function in healthy and depressed
      elderly.
AB  - OBJECTIVES: Late-life depression is known to correlate independently with
      decreased brain volumes in anterior cingulate, gyrus rectus and orbitofrontal
      cortex and with executive dysfunction, but the relationship between morphometry
      of reduced volume regions and executive dysfunction has not been well defined.
      METHODS: Nondepressed and depressed elders completed five executive tests, a
      standard panel of laboratory tests and magnetic resonance imaging. Images of the
      prefrontal cortex were manually masked and automatically segmented and regional
      brain volumes were calculated. Executive scores and error rates were regressed on
      bilateral white and gray matter volumes of anterior cingulate, gyrus rectus and
      orbitofrontal. RESULTS: Gyrus rectus was associated positively with scores on
      sequencing and nonverbal abstract reasoning, and negatively with two fluency
      error scores. Four positive interactions indicated that performance of controls
      was more closely associated with increased volume than that of depressed
      patients. Anterior cingulate was associated positively with two nonverbal
      reasoning tasks and with three positive interactions. Orbitofrontal volumes were
      negatively associated with correct responses and errors on two fluency tasks. One
      interaction showed controls' performance decreased more than depressed patients
      with increased volume. CONCLUSIONS: Individual executive tasks correlate
      positively with volumes of anterior cingulate and gyrus rectus regions and
      negatively with orbitofrontal region. The orbitofrontal relationship suggests a
      loss of inhibitory control with decreased volume because both correct and
      incorrect answers on fluency tasks increased per unit decrease in volume.

PMID- 18819163
TI  - Dimensional approach to delusions in psychotic depression in the elderly: factor
      structure and clinical correlates.
AB  - OBJECTIVE: The present study attempted to investigate the clinically important
      broader dimensions of clinical characteristics of delusions, through multivariate
      analysis, in a pure sample of elderly unipolar delusional depressives as well as
      to test their external validity against a set of demographic, anamnestic and
      psychopathological validators. METHODS: Fifty inpatients suffering from psychotic
      major depression (PMD) in the context of major depressive disorder, 60 years old
      or older, were assessed on the basis of SCID IV, HRSD, MMSE and by three-point
      ordinal scales of 12 clinical, intrinsic or relational characteristics of
      delusions tested for their inter-rater reliability. RESULTS: Principal Component
      Analysis resulted in the extraction of five factors, jointly accounting for 69.7%
      of the total variance. The five factors were interpreted as representing the
      dimensions of delusional strength, acute upsetting, delusional organization,
      incomprehensibility and incitation to actions. Most of the factors were
      differentially associated with patients' demographic, anamnestic and clinical
      variables. CONCLUSION: Our results overlap in part with those of another similar
      study in delusional depressives of all age-ranges, differing, however, in
      respects possibly attributable to peculiarities of elderly depressives. Overall,
      the findings of the present study contribute to the further elucidation of major
      clinical dimensions of delusions in PMD in the elderly and the testing of their
      external validity.

PMID- 18819164
TI  - Effect of guava (Psidium guajava Linn.) leaf soluble solids on glucose metabolism
      in type 2 diabetic rats.
AB  - This study investigated the effect of aqueous and ethanol soluble solid extracts
      of guava (Psidium guajava Linn.) leaves on hypoglycemia and glucose metabolism in
      type 2 diabetic rats. Low-dose streptozotocin (STZ) and nicotinamide were
      injected into Sprague-Dawley (SD) rats to induce type 2 diabetes. Acute and long
      term feeding tests were carried out, and an oral glucose tolerance test (OGTT) to
      follow the changes in plasma glucose and insulin levels was performed to evaluate
      the antihyperglycemic effect of guava leaf extracts in diabetic rats.The results
      of acute and long-term feeding tests showed a significant reduction in the blood
      sugar level in diabetic rats fed with either the aqueous or ethanol extract of
      guava leaves (p < 0.05). Long-term administration of guava leaf extracts
      increased the plasma insulin level and glucose utilization in diabetic rats. The
      results also indicated that the activities of hepatic hexokinase,
      phosphofructokinase and glucose-6-phosphate dehydrogenase in diabetic rats fed
      with aqueous extracts were higher than in the normal diabetic group (p < 0.05).
      On the other hand, diabetic rats treated with the ethanol extract raised the
      activities of hepatic hexokinase and glucose-6-phosphate dehydrogenase (p < 0.05)
      only. The experiments provided evidence to support the antihyperglycemic effect
      of guava leaf extract and the health function of guava leaves against type 2
      diabetes.

PMID- 18819165
TI  - The application of client-centred occupational therapy for Korean children with
      developmental disabilities.
AB  - The aim of this paper was to investigate the effectiveness of client-centred
      occupational therapy using the Canadian Occupational Performance Measure (COPM)
      and the Assessment of Motor and Process Skills (AMPS). Eight girls and 23 boys
      from Korea, with developmental disabilities and from 3 to 10 years of age
      participated in this study. Each child participated in 20 to 24 sessions of
      client-centred occupational therapy. Both the COPM and the AMPS change scores
      demonstrated statistically significant improvement (p < 0.01) in occupational
      performance. Significant correlations were found between COPM - Performance and
      AMPS - Motor skills (r(s) = 0.64, p < 0.05), and COPM - Satisfaction and AMPS -
      Process skills (r(s) = 0.62, p < 0.05) in a group positive towards client-centred
      occupational therapy. The COPM was a valuable tool in guiding and measuring the
      client-centred occupational therapy for children with developmental disabilities.
      The small sample size of 31 children limits the generalizability of the study's
      results. Future research needs to use a larger and more diverse sample of
      children to further validate the effectiveness of client-centred occupational
      therapy.

PMID- 18819166
TI  - Early home-based intervention in the Netherlands for children at familial risk of
      dyslexia.
AB  - Dutch children at higher familial risk of reading disability received a home
      based intervention programme before formal reading instruction started to
      investigate whether this would reduce the risk of dyslexia. The experimental
      group (n=23) received a specific training in phoneme awareness and letter
      knowledge. A control group (n=25) received a non-specific training in morphology,
      syntax, and vocabulary. Both interventions were designed to take 10 min a day, 5
      days a week for 10 weeks. Most parents were sufficiently able to work with the
      programme properly. At post-test the experimental group had gained more on
      phoneme awareness than the control group. The control group gained more on one of
      the morphology measures. On average, these specific training results did not lead
      to significant group differences in first-grade reading and spelling measures.
      However, fewer experimental children scored below 10th percentile on word
      recognition.

PMID- 18819167
TI  - Nanoscale control of near-infrared fluorescence enhancement using Au nanoshells.

PMID- 18819168
TI  - Biocompatible polymer-nanoparticle-based bimodal imaging contrast agents for the
      labeling and tracking of dendritic cells.

PMID- 18819169
TI  - Nature of atomic and molecular nitrogen configurations in TiO2-xNx nanotubes and
      tailored energy-storage performance on selective doping of atomic N states.

PMID- 18819170
TI  - SNPs: introduction and two-point mapping.

PMID- 18819172
TI  - An interview with... Nina Fedoroff. Interview by Errol C. Friedberg.

PMID- 18819171
TI  - Neuropeptides.
AB  - The role of neuropeptides in modulating behavior is slowly being elucidated. With
      the sequencing of the C. elegans genome, the extent of the neuropeptide genes in
      C. elegans can be determined. To date, 113 neuropeptide genes encoding over 250
      distinct neuropeptides have been identified. Of these, 40 genes encode insulin
      like peptides, 31 genes encode FMRFamide-related peptides, and 42 genes encode
      non-insulin, non-FMRFamide-related neuropeptides. As in other systems, C. elegans
      neuropeptides are derived from precursor molecules that must be post
      translationally processed to yield the active peptides. These precursor molecules
      contain a single peptide, multiple copies of a single peptide, multiple distinct
      peptides, or any combination thereof. The neuropeptide genes are expressed
      extensively throughout the nervous system, including in sensory, motor, and
      interneurons. In addition, some of the genes are also expressed in non-neuronal
      tissues, such as the somatic gonad, intestine, and vulval hypodermis. To address
      the effects of neuropeptides on C. elegans behavior, animals in which the
      different neuropeptide genes are inactivated or overexpressed are being isolated.
      In a complementary approach the receptors to which the neuropeptides bind are
      also being identified and examined. Among the knockout animals analyzed thus far,
      defects in locomotion, dauer formation, egg laying, ethanol response, and social
      behavior have been reported. These data suggest that neuropeptides have a
      modulatory role in many, if not all, behaviors in C. elegans.

PMID- 18819174
TI  - [Acute coronary syndromes at the heart of therapeutic progress in coronary artery
      disease].

PMID- 18819173
TI  - Reduced renal function and sleep-disordered breathing in community-dwelling
      elderly men.
AB  - BACKGROUND: Sleep-disordered breathing (SDB) may increase the risk of
      cardiovascular disease (CVD) and death in chronic kidney disease (CKD). However,
      the association between mild reductions in renal function and SDB is uncertain.
      METHODS: We studied 508 community-dwelling men aged>or=67 years (mean 76.0+/-5.3)
      who were enrolled at the Minnesota site for the Minneapolis center of the
      Outcomes of Sleep Disorders in Older Men (MrOS) sleep study and had serum
      cystatin-C and creatinine measured coincident with overnight polysomnography. CKD
      was defined as estimated glomerular filtration rate (eGFR)<60 ml/min/1.73 m2
      using Cockcroft-Gault (CG), modification of diet in renal disease (MDRD) and Mayo
      Clinic formulae. SDB was defined by a respiratory disturbance index (RDI)>or=15
      events/h. RESULTS: Mean cystatin-C was 1.21+/-0.30 mg/L, and mean creatinine was
      1.09+/-0.23 mg/dL. Median RDI was 7.0 events/h (range 0-73). Higher quartiles of
      cystatin-C were associated with higher mean RDI (p for trend=0.007). This
      association persisted after adjustment for age and race (p for trend=0.03), but
      not after adjustment for body mass index (BMI, p for trend=0.34). After adjusting
      for age, race, BMI, diabetes, hypertension, and CVD, CKD defined by the Mayo
      Clinic formula, but not CG or MDRD, was associated with a higher odds of SDB
      [odds ratio (OR) 1.95, 95% confidence interval (CI) 1.04-3.65, p=0.04].
      CONCLUSIONS: Older men with reduced renal function as defined by higher cystatin
      C concentration have higher average RDI. This effect is explained by higher BMI
      in men with higher cystatin-C. CKD defined by the Mayo Clinic formula is
      independently associated with twofold higher odds for SDB. Therefore, reduced
      renal function may be associated with SDB in older men.

PMID- 18819175
TI  - Disease modification in migraine: study design and sample size implications.
AB  - OBJECTIVE: Describe a clinical trial design that is capable of detecting disease
      modifying effects (DME) of anti-migraine drugs, and to explore the effect on
      study size of the likely variability in initial active- and placebo-response
      rates. METHODS: An orthodox power calculation and typical response rates in
      studies of prophylactic drugs for migraine were used to construct the initial
      model. The interactions between variability in response rates for active and
      placebo treatments (ARR and PRR, respectively), as well as required sample size,
      was then analyzed as a 3-dimensional problem. RESULTS: Overall, the putative
      study design requires 4 times as many patients as in each analyzable treatment
      group, all with allowances for loss to follow up, when both positive and negative
      control groups are available for comparison with the group being tested for DME.
      For an example prophylactic agent with ARR = 50% and PRR = 25%, the model
      suggests that the study might need 260-270 patients. Sample sizes increase in
      quasi-exponential manner as placebo-response rates rise, and active-response
      rates fall, and these are plotted for the reported variability of ARR and PRR in
      migraine prophylaxis. CONCLUSIONS: Variations on the study design can be modeled
      for the likely variability in outcome using a straightforward technique.
      Investigating DME activity for drugs with the efficacy that is typical of
      approved prophylactic agents might not require impractically large numbers of
      patients. Such models can be used not only in study design, but also in assessing
      the overall feasibility of whether or not to pursue DME detection within a given
      development program.

PMID- 18819176
TI  - D-dimer as the sole screening test for acute aortic dissection: a review of the
      literature.
AB  - Recent studies have proposed the use of D-dimer as a screening tool to "rule out"
      acute aortic dissection, claiming a sensitivity approaching 100%. We reviewed the
      literature to determine whether D-dimer can be used as the sole screening tool
      for acute aortic dissection. An Ovid MEDLINE search, 1966 to present, was
      performed with the key words "aortic dissection," "fibrin degradation products,"
      and "D-dimer," limited to "human" and "English language." Ten original research
      articles were identified that directly addressed the use of D-dimer in acute
      aortic dissection. There appears to be a subset of patients with acute aortic
      dissection who develop intramural hematomas, frequently found to have low or
      negative D-dimer levels. In addition, none of the studies reviewed defined a
      specific patient population eligible for D-dimer screening, and many of the
      studies had wide sensitivity confidence intervals (CIs) because of low patient
      numbers. Despite a high sensitivity, D-dimer cannot be recommended as the sole
      screening tool for acute aortic dissection. Ten per 100,000 Americans will have
      an acute aortic dissection, and missing the diagnosis may be catastrophic. A
      definitive diagnosis of aortic dissection largely relies on advanced radiographic
      imaging, either invasive or noninvasive. However, 38% of dissections are missed
      on initial evaluation, and there are no validated clinical decision rules for the
      clinical diagnosis of acute aortic dissection. Clinical suspicion and chest
      radiograph findings were the only tools for determining which patients require
      further imaging until recent studies proposed the use of D-dimer as a screening
      tool for acute aortic dissection, claiming a sensitivity approaching 100%. Our
      goal was to evaluate the current literature for the use of D-dimer as the sole
      screening tool for acute aortic dissection.

PMID- 18819177
TI  - Acute migraine treatment with oral triptans and NSAIDs in a managed care
      population.
AB  - OBJECTIVE: To describe the use of oral triptans with or without nonsteroidal anti
      inflammatory drugs (NSAIDs) for acute migraine treatment in a managed care
      population and its potential impact on functionality. BACKGROUND: Prescription or
      over-the-counter NSAIDs with or without oral triptans are commonly used for
      treatment of acute migraine pain. Little is known about patients' treatment
      strategy when they have had experiences using NSAIDs and oral triptan cotherapy
      and the relationship between treatment strategy and migraine symptoms and
      functionality. METHOD: Migraineurs identified from an administrative claims
      database were surveyed for their use of oral triptans and NSAIDs during their
      last attack in the screening phase and during the subsequent migraine attack in
      the follow-up phase of the study. Treatment regimens were classified into 6
      categories: simultaneous coadministration of triptans and NSAIDs (T and N);
      triptans first followed by NSAIDs (T N); NSAIDs first followed by triptans (N T);
      triptans only (TRP only); NSAIDs only (NSAID only); and others. Headache
      experience, reasons for treatment regimens, and treatment satisfaction were cross
      tabulated by treatment regimens. The log-rank test was used for the analysis of
      time-to-event data. RESULTS: Among 8440 oral triptan users surveyed during the
      screening phase, 2307 (27%) reported using triptans and NSAIDs combination
      therapy during their last migraine attack. Of those, 1502 experienced a
      subsequent migraine attack and completed the follow-up survey; 38% of these 1502
      patients who used triptans and NSAIDs cotherapy during their last migraine attack
      continued to use combination therapy for their next attack. The most common
      treatment regimen, excluding "others" (n = 354, 24%), was TRP only (n = 403,
      27%), followed by N T (n = 345, 23%), NSAID only (n = 170, 11%), T&N (n = 152,
      10%), and T N (n = 75, 5.0%). More TRP only patients became nausea-free within 1
      h after an initial dosing. TRP only, T&N, and N T had significantly shorter
      median hours of suffering from migraine and limited functioning, as compared with
      other treatment regimens. Substantially more patients taking TRP only (34.7%)
      were very satisfied with their current treatment regimen than other regimens.
      CONCLUSIONS: Migraine patients frequently change their treatment regimens in
      response to headache profiles. For patients with migraine associated nausea
      symptom, combination of therapy with triptan and NSAIDs appears to be less
      effective in relieving nausea than triptan monotherapy. Triptan montherapy
      remains a common and an effective migraine treatment strategy.

PMID- 18819178
TI  - Are prophylactic oral antibiotics indicated for the treatment of intraoral
      wounds?
AB  - Patients with intraoral and oral-cutaneous wounds commonly present to emergency
      departments (EDs), usually after sustaining blunt facial trauma. Many of these
      wounds are minor, small (<1 cm), hemostatic on presentation, and confined to the
      oral mucosa, requiring no specific intervention. Some of these injuries, however,
      do require wound repair, in particular large mucosal wounds (1 to 2 cm) and those
      that communicate with the overlying facial skin ("through-and-through" wounds).
      Most emergency medicine textbooks consider these larger wounds to be at
      significant risk for infection because of oral bacterial flora and thus recommend
      that a course of prophylactic antibiotics be prescribed when primary repair of
      these wounds is performed in the ED, in addition to routine oral and local wound
      care. However, studies have shown that other wounds commonly considered to be at
      significant risk for secondary infection, such as simple lacerations of the hand,
      do not appear to conclusively benefit from prophylactic antibiotic therapy when
      careful wound preparation is performed before primary repair. We therefore
      reviewed the available literature to determine the strength of evidence
      supporting the use of prophylactic oral antibiotics for intraoral wounds treated
      and repaired in the ED.

PMID- 18819179
TI  - Elimination of menstrual-related migraine beneficially impacts chronification and
      medication overuse.
AB  - OBJECTIVES: This study seeks to determine whether menstrual-related migraine
      (MRM) has a discrete, attributable impact on migraine chronicity and medication
      overuse. BACKGROUND: Menstrual-related migraine can be a disabling headache on
      its own; but when seen in headache clinics, it is often enmeshed in the setting
      of chronic migraine (CM) and medication overuse headache (MOH). Whereas
      nonspecific migraine preventives bestow their benefit uniformly, hormonal
      preventives (HPs)--when they are successful--address a discrete hormonal
      mechanism. They confer no known benefit to migraines that are not hormonally
      triggered. This selective property of HPs could potentially isolate MRM and
      segregate its effect on the overall clinical picture. METHODS: This is a
      retrospective review of 229 consecutive women seen in follow-up for hormonal
      prevention of MRM at an academic headache center. Patients kept standardized
      diaries from which separate menstrual-week (MW) and nonmenstrual week (nonMW)
      headache indices were calculated and compared. Resolution of MRM was defined by
      reduction of the MW headache index to a score not exceeding the nonMW headache
      indices. Consumption of all acute and preventive agents used in the preceding
      month was tallied. We performed post-treatment comparisons of medication usage
      and headache characteristics among subjects in whom MRM was resolved and those in
      whom it was not resolved. RESULTS: At baseline, CM was present in 92% of
      subjects, 72% of whom also met criteria for MOH. Resolution of MRM was achieved
      in 81% of subjects who were compliant with HP and was associated with reversion
      to episodic migraine (59% vs 18%, P < .001) and resolution of medication overuse
      (54% vs 20%, P < .001). Resolution of MRM was associated with significant
      decreases in per capita consumption of triptans, opioids, all acute agents, and
      migraine preventive medications. CONCLUSIONS: Resolution of MRM correlated not
      only with conversion of CM to an episodic pattern, but also with a significant
      reduction in medication usage. It offers preliminary evidence that hormonal
      regimens may have a beneficial role in prevention of MRM.

PMID- 18819180
TI  - [The evidence of clinical effects of ezetimibe is not sufficient].

PMID- 18819181
TI  - National Highway Traffic Safety Administration (NHTSA) notes.

PMID- 18819182
TI  - Cortical spreading edema in persistent visual migraine aura.
AB  - We present imaging evidence of the spreading of cortical edema with reversibly
      restricted water diffusion from the left occipital to the temporoparietal cortex
      in persistent visual migraine aura in a 58-year-old man. The right-sided visual
      field defect lasting for 15 days was associated with discoupling of glucose
      metabolism and blood flow and the decreased apparent diffusion coefficient also
      suggested cytotoxic edema. At 8 weeks no signs were present, and magnetic
      resonance imaging became normal; therefore, long-lasting restricted cortical
      water diffusion, even if coupled with hypometabolism and edema, can be reversible
      in persistent visual migraine aura.

PMID- 18819183
TI  - Reversible imaging abnormalities consistent with CSD during migraine without aura
      attack.
AB  - An 18-year-old man with a history of migraine without aura and normal
      neurological examination carried out a cerebral CT scan during a spontaneous
      typical migraine attack. While the CT scan demonstrated left temporal-parietal
      occipital low attenuation, a brain magnetic resonance imaging, performed 5 days
      later, did not show any lesions. Based on this evidence, we can speculate that
      the dysfunction of the cerebrovascular system, either in the cerebral cortex or
      in the subcortical regions, is an important mechanism in the pathophysiology of
      migraine.

PMID- 18819184
TI  - Functional MRI in malformations of cortical development: activation of dysplastic
      tissue and functional reorganization.
AB  - BACKGROUND AND PURPOSE: Functional neuroimaging and electrophysiological studies
      suggest that dysplastic neural tissue in malformations of cortical development
      may participate in task performance, and that functional organization can be
      altered beyond visible lesion boundaries. The aim of this work was to investigate
      cortical function in a heterogeneous group of patients with malformations of
      cortical development. METHODS: Twelve patients participated in the study, 2 for
      each of the following categories: subcortical, periventricular, and band
      heterotopia, unilateral and bilateral polymicrogyria, and focal cortical
      dysplasia. Functional magnetic resonance imaging was performed with finger
      tapping, somatosensory and visual stimulation, and language-related tasks.
      RESULTS: We found activations within the dysplastic tissue in subcortical
      heterotopia, band heterotopia, and polymicrogyria, but not in periventricular
      heterotopic nodules. In one of the patients with focal cortical dysplasia,
      language-related activation involved part of the lesion. Functional
      reorganization beyond visible lesion boundaries was seen, with different
      patterns, in 4 patients. CONCLUSIONS: In accordance with previous reports, our
      findings indicate that dysplastic neural tissue can be activated during task
      performance, and that in some patients, extensive functional reorganization
      occurs, highlighting the importance of functional magnetic resonance imaging in
      presurgical planning in those patients for whom epilepsy surgery is considered as
      an option.

PMID- 18819185
TI  - A progressive neurologic disorder with multiple CNS lesions: a neuroimaging
      clinicopathologic correlation. Progressive multifocal leukoencephalopathy (PML).
AB  - A 51-year-old man with a diagnosis of myelodysplasia and non-Hodgkin's lymphoma
      underwent an unmatched allogenic bone marrow transplantation and was treated
      posttransplant with chronic immunosuppressive medication. Eight months following
      transplantation, he presented with progressive dysarthria, cognitive and visual
      decline. Evaluation included brain magnetic resonance (MR) imaging demonstrating
      multifocal areas of increased T2 and FLAIR (fluid attenuated inversion recovery)
      signals involving the left frontal, parietal, and occipital lobes. The MR lesions
      demonstrated diffuse increased signal on DWI (diffusion-weighted images) and
      normal to low signal on ADC (apparent diffusion coefficients). Contrast-enhanced
      T1 images were unremarkable. Lumbar puncture revealed a mild elevation in
      cerebrospinal fluid (CSF) protein. CSF PCR assay for viral DNA fragments were
      negative on two occasions. Serum serology for HIV was negative as well. A brain
      biopsy was subsequently performed. The clinical and neuroimaging differential
      diagnoses as well as neuropathologic correlation are presented.

PMID- 18819186
TI  - Proceedings of the 2nd International Symposium on Kallikreins and Kallikrein
      Related Peptidases, 16-28 October 2007, Santorini, Greece.

PMID- 18819187
TI  - BIOCOMP 2007. Proceedings of the International Conference on Collective Dynamics:
      Topics on Competition and Cooperation in the Biosciences. 24-28 September 2007,
      Vietri, Italy.

PMID- 18819188
TI  - Proceedings of the 10th International Conference on Endothelin, 16-19 September
      2007, Bergamo, Italy.

PMID- 18819189
TI  - Proceedings of the 2007 AAOS/NIH Osteolysis and Implant Wear: Biological,
      Biomedical Engineering, and Surgical Principles Research Symposium, November 9
      11, 2007, Austin, Texas, USA.

PMID- 18819191
TI  - Michael A. Raftery (1936-2007)--the first enzyme  mechanism, sequential
      cooperativity, and the nicotinic  acetylcholine receptor defined.

PMID- 18819192
TI  - Drumsticks.

PMID- 18819190
TI  - Regulation of neural progenitor cell development in the nervous system.
AB  - The mammalian telencephalon, which comprises the cerebral cortex, olfactory bulb,
      hippocampus, basal ganglia, and amygdala, is the most complex and intricate
      region of the CNS. It is the seat of all higher brain functions including the
      storage and retrieval of memories, the integration and processing of sensory and
      motor information, and the regulation of emotion and drive states. In higher
      mammals such as humans, the telencephalon also governs our creative impulses,
      ability to make rational decisions, and plan for the future. Despite its massive
      complexity, exciting work from a number of groups has begun to unravel the
      developmental mechanisms for the generation of the diverse neural cell types that
      form the circuitry of the mature telencephalon. Here, we review our current
      understanding of four aspects of neural development. We first begin by providing
      a general overview of the broad developmental mechanisms underlying the
      generation of neuronal and glial cell diversity in the telencephalon during
      embryonic development. We then focus on development of the cerebral cortex, the
      most complex and evolved region of the brain. We review the current state of
      understanding of progenitor cell diversity within the cortical ventricular zone
      and then describe how lateral signaling via the Notch-Delta pathway generates
      specific aspects of neural cell diversity in cortical progenitor pools. Finally,
      we review the signaling mechanisms required for development, and response to
      injury, of a specialized group of cortical stem cells, the radial glia, which act
      both as precursors and as migratory scaffolds for newly generated neurons.

PMID- 18819193
TI  - Proceedings of the EMECS 7/ECSA 40 Conference, Caen, France, May 2006.

PMID- 18819194
TI  - "Classic" approach yields best results in AFib surgery.  Blocking more electrical
      paths in the heart reduces abnormal rhythms.

PMID- 18819195
TI  - Healthy kidneys may reduce risk of sudden cardiac death. Find out your particular
      risk factors and learn how to protect both your kidneys and your heart.

PMID- 18819197
TI  - Age no bar to routine mammography.  Evidence is accumulating that women in their
      70s and beyond can benefit from regular mammograms.  What does that mean for you?

PMID- 18819196
TI  - Simple changes in diet can mean big cholesterol reduction. Limiting your intake
      of saturated fats, processed meals and high-cholesterol foods such as eggs
      provides key health benefits.

PMID- 18819198
TI  - Travel tips. Ways to minimize jet lag.

PMID- 18819199
TI  - What to do about fibroids. New options for managing troublesome fibroids continue
      to appear. Here's help in finding what's best for you.

PMID- 18819201
TI  - Outbreak news. Cholera, Iraq.

PMID- 18819200
TI  - Anxiety and physical illness.  Understanding and treating anxiety can often
      improve the outcome of chronic disease.

PMID- 18819202
TI  - Outbreak news. Melamine-contaminated powdered infant formula, China.

PMID- 18819203
TI  - Progress towards eliminating measles in Japan, 2008.

PMID- 18819204
TI  - Prevention of unplanned perioperative hypothermia.
AB  - Hypothermia is one of the most common complications experienced by surgical
      patients. Better postoperative patient outcomes are achieved when normothermia is
      maintained. Perioperative nurses should understand how to maintain normothermia,
      the causes of hypothermia, and adverse patient outcomes that result from
      hypothermia. Nursing interventions to help prevent hypothermia can be implemented
      during each phase of perioperative care.

PMID- 18819205
TI  - Laparoscopic-assisted colon surgery.
AB  - Laparoscopic-assisted colon surgery is a safe alternative to conventional open
      colectomy. Using the laparoscopic approach, the surgeon uses tools through port
      sites to mobilize the section of colon to be removed, avoiding a large laparotomy
      incision. Usually, two to three 5-mm port site are created. Although this
      procedure often requires a small incision to remove the diseased portion of the
      colon, the incision is much smaller, causing less postoperative pain and
      shortening the hospital stay. This leads to a faster return to activities of
      daily living for the patient.

PMID- 18819206
TI  - Dealing with a "surgical personality".

PMID- 18819208
TI  - [Rearing children of multiple births and public health problems].

PMID- 18819207
TI  - [Basis for clinical economics (13)].

PMID- 18819209
TI  - [Importance of life activity evaluation in daily lives].

PMID- 18819210
TI  - Do your root cause analyses fail to improve safety? Take these steps.

PMID- 18819211
TI  - What if physicians don't believe your quality data?

PMID- 18819212
TI  - Patient satisfaction planner. New care model transforms facility.

PMID- 18819214
TI  - Almost 50% of docs don't know how to report errors.

PMID- 18819213
TI  - Patient satisfaction planner. Radiology lab speeds throughput with Six Sigma.

PMID- 18819215
TI  - Florida hospital cuts failed pediatric sedation rate 98%.

PMID- 18819216
TI  - Christiana slashes sepsis mortality rate.

PMID- 18819217
TI  - An autopsy case of poisoning with ethanol and psychotropic drugs.
AB  - A case of fatal poisoning involving ethanol with psychotropic drugs is presented.
      Quantitative toxicological analysis showed that the concentrations of ethanol,
      amoxapine and phenobarbital in the femoral blood were 2.86 mg/ml, 0.41 microg/ml
      and 6.80 microg/ml, respectively. We concluded that the cause of death was due to
      the combination use of ethanol, amoxapine and phenobarbital.

PMID- 18819218
TI  - [Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) as a cause of
      sudden death].
AB  - Common cause of sudden death in children and teenagers are primary
      cardiomyopathies, mostly hypertrophic. The authors refer to arrhythmogenic right
      ventricular dysplasia/cardiomyopathy as a possible cause of sudden death. The
      disease is not limited to the right hearth only, the presence of fat and scar
      tissue in the in the hearth muscle is variable.

PMID- 18819219
TI  - [The technological screening of beers, made in Slovak Republic, in the view of
      forensic alcohology].
AB  - The questions connected with forensic alcohology are closely bounded with the
      legal norms and actual production of alcoholic beverages, incl. the breweries.
      The presented work, dealing with the beers being made in Slovak republic, had
      been stipulated by the Slovak Society of Forensic Medicine, in the aim to inform
      the forensic experts about the beers being produced in the country mentioned.

PMID- 18819220
TI  - Advances in photoprotection.
AB  - Major advancements in the realm of photoprotection have occurred over the last
      decade providing potential means to reduce the prevalence of ultraviolet
      radiation-related skin problems. This review elucidates current photoprotective
      methods and recent developments that may hold future promise.

PMID- 18819221
TI  - The neutrophilic dermatoses.
AB  - The neutrophilic dermatoses (ND) may present with pustules, plaques, ulcerations,
      and general malaise. They are secondary to the invasion of the skin by normal
      polymorphonuclear leukocytes in the absence of infection. ND are often associated
      with particular systemic diseases. The management of affected patients is
      reviewed, with a focus on nursing care.

PMID- 18819222
TI  - What's your assessment? Pityrosporum folliculitis.

PMID- 18819223
TI  - Give them a hand: patients with hand and foot psoriasis require special
      attention.
AB  - Hand and foot psoriasis impairs patients' ability to function, impacts them
      financially, and chips away at their self-worth. Dermatology nurses play an
      important role with these patients in improving their quality of life through
      support, counsel, education, and meeting their medical and emotional needs.

PMID- 18819224
TI  - Accurately diagnosing commonly misdiagnosed circular rashes.
AB  - Rashes are common in the pediatric population yet can be quite problematic for
      nurse practitioners to diagnose. A thorough history and physical examination,
      along with some simple procedures, will aid in identifying these skin conditions.
      Four cases are presented, which may initially prove challenging to diagnose, and
      symptoms are categorically examined to arrive at the accurate diagnoses.
      Treatment guidelines, options, and the role of parental education and involvement
      also are discussed.

PMID- 18819225
TI  - Living with psoriasis.

PMID- 18819226
TI  - Cutaneous blastomycosis.

PMID- 18819227
TI  - The monster in the server room.

PMID- 18819228
TI  - Understanding medical assistant practice liability issues.

PMID- 18819229
TI  - Leadership, civility, and the 'no jerks' rule.
AB  - Nursing organizations and hospitals are not immune from the ravages of
      incivility. Toxic behavior can range from the very serious bullying and sabotage
      of very destructive people to the annoying and hard to cope behavior of just
      plain jerks. When a practice does not have a clearly defined "No Jerk" rule and
      infrastructure to support healthy behavior, communication suffers and errors
      occur. Nurse leaders have the opportunity of changing the self-interest behavior
      of jerks in our communities of caring.

PMID- 18819231
TI  - [See the thinking brain: a story about water].
AB  - Among the astonishing Einstein's papers from 1905, there is one which
      unexpectedly gave birth to a powerful method to explore the brain. Molecular
      diffusion was explained by Einstein on the basis of the random translational
      motion of molecules which results from their thermal energy. In the mid 1980s it
      was shown that water diffusion in the brain could be imaged using MRI. During
      their random displacements water molecules probe tissue structure at a
      microscopic scale, interacting with cell membranes and, thus, providing unique
      information on the functional architecture of tissues. A dramatic application of
      diffusion MRI has been brain ischemia, following the discovery that water
      diffusion drops immediately after the onset of an ischemic event, when brain
      cells undergo swelling through cytotoxic edema. On the other hand, water
      diffusion is anisotropic in white matter, because axon membranes limit molecular
      movement perpendicularly to the fibers. This feature can be exploited to map out
      the orientation in space of the white matter tracks and image brain connections.
      More recently, it has been shown that diffusion MRI could accurately detect
      cortical activation. As the diffusion response precedes by several seconds the
      hemodynamic response captured by BOLD fMRI, it has been suggested that water
      diffusion could reflect early neuronal events, such as the transient swelling of
      activated cortical cells. If confirmed, this discovery will represent a
      significant breakthrough, allowing non invasive access to a direct physiological
      marker of brain activation. This approach will bridge the gap between invasive
      optical imaging techniques in neuronal cell cultures, and current functional
      neuroimaging approaches in humans, which are based on indirect and remote blood
      flow changes.

PMID- 18819232
TI  - [An ionic determination of the insulinotropic action of insulin: not everyone
      agrees].
AB  - A recent model concerning the ionic determinants involved in the insulinotropic
      action of nutrients, namely an anion channel hypothesis, is presented, and
      selected experimental findings in support of such a model, are reviewed.

PMID- 18819233
TI  - [Physiopathologic aspects of anemia and thrombocytopenia in children with
      cancers: the roles of erythropoietin and thrombopoietin].
AB  - Physiopathology of anaemia and thrombocytopaenia in children with malignancy: the
      role of erythropoietin and thrombopoietin. The aim of our work was to determine
      the role of an impaired erythropoietin (EPO) and thrombopoietin (TPO) production
      in development of, respectively, the anaemia and thrombocytopaenia in children
      with malignancy. Simultaneous dosage of EPO and of serum transferrin receptor
      have shown that anaemia in these patients is of central origin but related to a
      blunted EPO production. The same observation has been made in children at
      diagnosis either with acute leukaemia or solid tumour as well as during
      chemotherapy. In patients under maintenance chemotherapy for acute leukaemia,
      using long-term bone marrow cultures, we could detect an impaired supportive
      capacity of bone marrow micro-environment for erythropoiesis. The last part of
      this work has shown that thrombocytopaenia associated with acute leukaemia in
      children is accompanied by very high TPO levels as observed in other
      thrombocytopaenia of central origin, excepted in patients with acute leukaemia of
      myeloid origin. In these patients, TPO levels are inappropriately low in most
      cases. The low TPO levels are related to the presence of TPO receptor-expressing
      myeloid leukaemic cells, suggesting that TPO is "consumed" by blast cells
      expressing a functional TPO receptor.

PMID- 18819234
TI  - Evaluating vasal occlusion methods for vasectomy.

PMID- 18819235
TI  - Dermoscopy: an invaluable tool for evaluating skin lesions.

PMID- 18819236
TI  - Aortic stenosis: diagnosis and treatment.
AB  - Aortic stenosis is the most important cardiac valve disease in developed
      countries, affecting 3 percent of persons older than 65 years. Although the
      survival rate in asymptomatic patients with aortic stenosis is comparable to that
      in age- and sex-matched control patients, the average overall survival rate in
      symptomatic persons without aortic valve replacement is two to three years.
      During the asymptomatic latent period, left ventricular hypertrophy and atrial
      augmentation of preload compensate for the increase in afterload caused by aortic
      stenosis. As the disease worsens, these compensatory mechanisms become
      inadequate, leading to symptoms of heart failure, angina, or syncope. Aortic
      valve replacement should be recommended in most patients with any of these
      symptoms accompanied by evidence of significant aortic stenosis on
      echocardiography. Watchful waiting is recommended for most asymptomatic patients,
      including those with hemodynamically significant aortic stenosis. Patients should
      be educated about symptoms and the importance of promptly reporting them to their
      physicians. Serial Doppler echocardiography is recommended annually for severe
      aortic stenosis, every one or two years for moderate disease, and every three to
      five years for mild disease. Cardiology referral is recommended for all patients
      with symptomatic aortic stenosis, those with severe aortic stenosis without
      apparent symptoms, and those with left ventricular dysfunction. Many patients
      with asymptomatic aortic stenosis have concurrent cardiac conditions, such as
      hypertension, atrial fibrillation, and coronary artery disease, which should also
      be carefully managed.

PMID- 18819237
TI  - Information from your family doctor. Aortic stenosis: what you should know.

PMID- 18819238
TI  - Management of mastitis in breastfeeding women.
AB  - Mastitis occurs in approximately 10 percent of U.S. mothers who are
      breastfeeding, and it can lead to the cessation of breastfeeding. The risk of
      mastitis can be reduced by frequent, complete emptying of the breast and by
      optimizing breastfeeding technique. Sore nipples can precipitate mastitis. The
      differential diagnosis of sore nipples includes mechanical irritation from a poor
      latch or infant mouth anomalies, such as cleft palate or bacterial or yeast
      infection. The diagnosis of mastitis is usually clinical, with patients
      presenting with focal tenderness in one breast accompanied by fever and malaise.
      Treatment includes changing breastfeeding technique, often with the assistance of
      a lactation consultant. When antibiotics are needed, those effective against
      Staphylococcus aureus (e.g., dicloxacillin, cephalexin) are preferred. As
      methicillin-resistant S. aureus becomes more common, it is likely to be a more
      common cause of mastitis, and antibiotics that are effective against this
      organism may become preferred. Continued breastfeeding should be encouraged in
      the presence of mastitis and generally does not pose a risk to the infant. Breast
      abscess is the most common complication of mastitis. It can be prevented by early
      treatment of mastitis and continued breastfeeding. Once an abscess occurs,
      surgical drainage or needle aspiration is needed. Breastfeeding can usually
      continue in the presence of a treated abscess.

PMID- 18819239
TI  - Information from your family doctor. Mastitis: what you should know.

PMID- 18819240
TI  - Atypical moles.
AB  - Atypical moles can be distinguished visually by clinical features of size greater
      than 6 mm in diameter, color variegation, indistinct borders, and textured
      surface. All patients who have atypical moles should be counselled about sun
      avoidance, screening of family members, and regular skin checks at least once per
      year. Total body photography and dermoscopy can aid in regular skin monitoring
      for changes in atypical moles and the emergence of new lesions. The presence of
      multiple atypical moles increases the risk of melanoma. The greatest risk of
      melanoma is in patients who have more than 50 atypical moles and two or more
      family members with melanoma (familial atypical mole and melanoma syndrome).
      Atypical moles should be removed when they have features suggestive of malignant
      transformation. Elliptical excision is the preferred removal technique. Removing
      all atypical moles is neither necessary nor cost effective.

PMID- 18819241
TI  - Information from your family doctor. Atypical moles: what you should know.

PMID- 18819242
TI  - Drug-induced nephrotoxicity.
AB  - Drugs are a common source of acute kidney injury. Compared with 30 years ago, the
      average patient today is older, has more comorbidities, and is exposed to more
      diagnostic and therapeutic procedures with the potential to harm kidney function.
      Drugs shown to cause nephrotoxicity exert their toxic effects by one or more
      common pathogenic mechanisms. Drug-induced nephrotoxicity tends to be more common
      among certain patients and in specific clinical situations. Therefore, successful
      prevention requires knowledge of pathogenic mechanisms of renal injury, patient
      related risk factors, drug-related risk factors, and preemptive measures, coupled
      with vigilance and early intervention. Some patient-related risk factors for drug
      induced nephrotoxicity are age older than 60 years, underlying renal
      insufficiency (e.g., glomerular filtration rate of less than 60 mL per minute per
      1.73 m2), volume depletion, diabetes, heart failure, and sepsis. General
      preventive measures include using alternative non-nephrotoxic drugs whenever
      possible; correcting risk factors, if possible; assessing baseline renal function
      before initiation of therapy, followed by adjusting the dosage; monitoring renal
      function and vital signs during therapy; and avoiding nephrotoxic drug
      combinations.

PMID- 18819243
TI  - Procalcitonin-guided treatment of respiratory tract infections.

PMID- 18819245
TI  - Refractory focal seizures with progressive weakness in the right limbs. Rasmussen
      encephalitis.

PMID- 18819247
TI  - Cobalt protoporpyhrin reduces caspase-3,-7 enzyme activity in neonatal porcine
      islets, but does not inhibit cell death induced by TNF-alpha.
AB  - Apoptotic phenomena observed in vitro following isolation and following
      transplantation contribute significantly to islet graft loss. Strategies to
      reduce apoptosis of islet tissue prior to and posttransplantation may improve
      graft survival and function and reduce the amount of tissue necessary to achieve
      insulin independence. The expression of cytoprotective proteins is one such
      strategy that may prolong islet survival. In this light, heme-oxygenase 1 (HO-1)
      upregulation has been studied in both allo- and xenotransplantation models. In
      this study, the effect of HO-1 on apoptosis in neonatal porcine islet-like cell
      clusters (NPICC) was assessed. In in vitro assessments of NPICC apoptosis, NPICC
      showed a high sensitivity to apoptotic stimulation using a combination of TNF
      alpha and cycloheximide. Stimulation with TNF-alpha alone was sufficient to
      induce reproducible apoptotic responses as demonstrated by caspase-3,-7
      activation and subdiploid DNA analysis. Dose-dependent, high-level HO-1 protein
      expression was achieved following culture of NPICC in medium containing either
      cobalt protoporphyrin (CoPP) or cobalt mesoporphyrin (CoMP). CoPP treatment
      resulted in the reduction of caspase-3,-7 enzyme activity following TNF-alpha
      stimulation. However, such an effect was not associated with a reduction in the
      levels of cell death. Indeed, the inhibition of caspase enzyme activity resulted
      in decreased PARP-1 cleavage, which may lead to heightened levels of necrosis in
      treated NPICC cultures, possibly explaining the observed commitment of NPICC to
      the death pathway.

PMID- 18819248
TI  - Monotherapy with anti-LFA-1 monoclonal antibody promotes long-term survival of
      rat islet xenografts.
AB  - Previously we demonstrated that anti-LFA-1 monoclonal (mAb) could promote long
      term survival of discordant porcine islet xenografts in mice. The aim of this
      study, therefore, was to determine whether a shortterm administration of anti-LFA
      1 mAb would promote long-term survival of concordant rat islet xenografts in
      mice, and whether combining short-term administration of anti-LFA-1 mAb therapy
      with an immunosuppressive drug, rapamycin, would facilitate islet xenograft
      survival. Streptozotocin-induced diabetic BALB/c mice were transplanted with 500
      Wistar-Furth rat islets under the kidney capsule and were either left untreated
      or treated with short-term administration of rapamycin (0.2 mg/kg) alone, anti
      LFA-1 mAb (0.2 mg/ dose) alone, or a combination of rapamycin and anti-LFA-1 mAb
      using the same doses. All untreated mice rejected their grafts by 24 days
      posttransplantation with a mean graft survival time of 18.8 +/- 2.5 days
      posttransplantation (n = 5). All mice treated with rapamycin alone had prolonged
      islet graft survival but eventually rejected their islet grafts by 81 days
      posttransplantation. In contrast, the majority of the mice (27/ 28) treated with
      anti-LFA-1 mAb alone maintained long-term normoglycemia (>100 days). Rapamycin in
      combination with anti-LFA-1 mAb proved equally effective with 29 of 30 mice
      maintaining normoglycemia for more than 100 days posttransplantation. Low levels
      of mouse anti-rat antibodies, as well as a decrease in the degree of mononuclear
      cell infiltration of the islet graft, closely correlated with long-term islet
      xenograft survival. These results demonstrate that monotherapy with anti-LFA-1
      mAb is highly effective in promoting long-term survival of rat islet xenografts
      and that combination of anti-LFA-1 mAb with rapamycin does not facilitate nor
      abrogate the induction of long-term xenograft survival by anti-LFA-1 mAb therapy
      in BALB/c mice. Our study indicates that immunomodulation through mAb therapy
      could form a significant component of future antirejection therapies in clinical
      islet xenotransplantation.

PMID- 18819249
TI  - Viral IL-10 gene transfer prolongs rat islet allograft survival.
AB  - Islet transplantation is a potential cure for diabetes. However, allotransplant
      rejection severely limits its clinical application. In this study, we sought to
      transfect rat islets with an adenoviral vector containing the viral IL-10 (vIL
      10) gene and examine its efficacy in preventing graft rejection. The
      immunosuppressive effect of vIL-10 is reported but its efficacy is somehow
      debatable in transplantation model. vIL-10 transfected islets were transplanted
      into streptozotocin-induced diabetic rats. Blood glucose, serum vIL-10
      concentration, graft histology, and graft cytokine expression were used to
      monitor graft function up to day 21 after transplantation. Transfected islets
      released a large amount of vIL-10 protein without affecting their viability and
      functional integrity. When we transplanted the transfected islets into allogeneic
      hosts, the survival of grafted islets was not significantly increased. However,
      the combined use of vIL-10 and subtherapeutic doses of CsA (cyclosporine)
      significantly prolonged graft survival beyond that achieved with either agent
      alone (p < 0.001). vIL-10 and CsA-treated rats contain high level of vIL-10 in
      serum, which is evidenced by the inhibition of allogeneic mixed lymphocyte
      reaction (MLR). Histological analysis additionally revealed the presence of
      viable islets up to 21 days. IL-10 mRNA expression in grafted liver was higher
      and IFN-gamma mRNA was lower in vIL-10 and CsA-treated animals, compared with
      other groups. The synergistic effect of this combination therapy is potentially
      correlated with the induction of inhibitory cytokine secretion and downregulation
      of proinflammatory cytokine secretion from host cells.

PMID- 18819250
TI  - Mitomycin-C treatment followed by culture produces long-term survival of islet
      xenografts in a rat-to mouse model.
AB  - One of the goals of islet transplantation is to transplant viable islets without
      host immunosuppression. The present study was designed to determine whether
      pretreatment of islets with mitomycin-C (MMC) followed by culture enhances islet
      survival in a rat-to-mouse xenogeneic combination. WS(RT1k) rat islets pretreated
      with various concentrations of MMC (0, 3.2, 10, 32, 100, 320, and 1000 microg/ml)
      were tested for viability by in vitro insulin secretory capacity and vital
      staining of islets. The MMC-treated islets (10 microg/ml) cultured for various
      periods (4, 20, or 40 h, 3 or 7 days) were transplanted into the renal
      subcapsular space of STZ-induced diabetic C57BL/6 (B6: H-2b) mice. MMC-treated or
      nontreated islets were subjected to microarray gene analysis and
      immunohistological study. Evaluation of in vitro insulin secretory capacity and
      vital staining of islets indicated that MMC at a dose < or =32 microg/ml is
      nontoxic and preserves islet function. Marked prolongation of graft survival was
      noted with half of islet grafts surviving indefinitely (>100 days) when 10
      microg/ml of MMC-treated islets was transplanted after 40 h or 3 days in culture,
      but not when they were transplanted within 4 h following treatment or at 7 days
      following treatment, indicating that there is a critical culture period necessary
      for successful islet graft survival. Microarray analysis suggested possible genes
      for this prolongation with TGF-beta highly expressed in MMC-treated islets
      subjected to culture for 3 days. Our results indicate that MMC treatment followed
      by a critical culture period induces marked prolongation of rat islet xenograft
      survival in nonimmunosuppressed recipient mice, offering a strategy for islet
      transplantation without immunosuppression.

PMID- 18819251
TI  - Combination therapy with glucagon-like peptide-1 and gastrin induces beta-cell
      neogenesis from pancreatic duct cells in human islets transplanted in
      immunodeficient diabetic mice.
AB  - Pancreatic islet transplantation as a treatment for type 1 diabetes is limited by
      human donor tissue availability. We investigated whether the beta-cell mass in
      human isolated islets could be expanded by treatments with glucagon-like peptide
      1 (GLP-1) and gastrin, peptides reported to stimulate beta-cell growth in mice
      and rats with deficits in beta-cell mass. Human islets with low endocrine cell
      purity (7% beta-cells, 4% alpha-cells) and abundant exocrine cells (29% duct
      cells and 25% acinar cells) were implanted under the renal capsule of nonobese
      diabetic-severe combined immune deficiency (NOD-scid) mice made diabetic with
      streptozotocin. The mice were treated with GLP-1 and gastrin, separately and
      together, daily for 5 weeks. Blood glucose was significantly reduced only in mice
      implanted with human pancreatic cells and treated with GLP-1 plus gastrin.
      Correction of hyperglycemia was accompanied by increased insulin content in the
      human pancreatic cell grafts as well as by increased plasma levels of human C
      peptide in the mice. Immunocytochemical examination revealed a fourfold increase
      in insulin-positive cells in the human pancreatic cell grafts in GLP-1 plus
      gastrin-treated mice, and most of this increase was accounted for by the
      appearance of cytokeratin 19-positive pancreatic duct cells expressing insulin.
      We conclude that combination therapy with GLP-1 and gastrin expands the beta-cell
      mass in human islets implanted in immunodeficient diabetic mice, largely from
      pancreatic duct cells associated with the islets, and this is sufficient to
      ameliorate hyperglycemia in the mice.

PMID- 18819252
TI  - Exendin-4 treatment expands graft beta-cell mass in diabetic mice transplanted
      with a marginal number of fresh islets.
AB  - Exendin-4 stimulates insulin secretion, suppresses glucagons secretion, increases
      beta-cell replication and neogenesis, and reduces beta-cell apoptosis. However,
      it has been shown that posttransplant exendin-4 treatment did not improve glucose
      homeostasis in diabetic mice transplanted with a large number of freshly isolated
      islets. The aim of this study was to test if exendin-4 is beneficial for
      hyperglycemic recipients with a marginal number of fresh islets. We transplanted
      150 C57BL/6 mouse islets under the kidney capsule of inbred streptozotocin
      diabetic mice, and then treated the recipients with and without exendin-4 for 6
      weeks. Before and after transplantation, recipients' blood glucose, body weight,
      and intraperitoneal glucose tolerance test were measured. At 6 weeks, the grafts
      were removed to determine beta-cell mass. Blood glucose levels in both groups
      decreased progressively after transplantation, and the exendin-4-treated group
      had had lower blood glucose than controls since day 3. By 6 weeks, euglycemia was
      achieved more in mice treated with exendin-4 than in controls (100% vs. 62.5%, p
      = 0.018). The time to obtain normoglycemia was shorter in the exendin-4-treated
      group than in controls (12 +/- 8 vs. 29 +/- 13 days, p < 0.001). Blood glucose at
      6 weeks was 123 +/- 18 and 170 +/- 62 mg/dl in the exendin-4-treated group and
      controls, respectively (p = 0.008). Additionally, the exendin-4-treated group had
      better glucose tolerance than controls at 2 and 4 weeks (p <0.02). However, both
      groups exhibited increased body weight over time, and weight changes did not
      significantly differ between the two groups throughout the study period. At 6
      weeks after transplantation, grafts in the exendin-4-treated group were more
      prominent and contained more insulin-stained cells than those of controls. They
      had 2.3-fold beta-cell mass of the graft compared with controls (0.30 +/- 0.11
      vs. 0.13 +/- 0.03 mg, p = 0.012). These results indicate posttransplant exendin-4
      treatment in the diabetic recipient with a marginal number of fresh islets
      expands graft beta-cell mass and improves transplantation outcome.

PMID- 18819253
TI  - Analysis of donor- and isolation-related variables from non-heart-beating donors
      (NHBDs) using the Kyoto islet isolation method.
AB  - Recently, we demonstrated that islet transplantation from non-heart-beating
      donors (NHBDs) using the Kyoto islet isolation method (KIIM) successfully
      reversed patients' diabetes state. In this study, we evaluated the effects of
      donor- and isolation-related variables on islet isolation results from NHBDs by
      KIIM. Twenty-one islet preparations from the pancreata of NHBDs were isolated by
      KIIM. Islet preparations that met transplantation criteria and achieved improved
      patient diabetes control after transplantation were defined as successful
      isolations. Potential risk factors deemed to affect islet isolation results, such
      as age, gender, body mass index, hospital stay, donors' blood biochemical tests,
      a modified pancreata procurement method, and isolation and purification procedure
      related variables, were analyzed. Seventeen out of 21 islet isolations (81%) were
      successful isolations. Postpurification islet yield was 447,639 +/- 39,902 islet
      equivalents (IE) in the successful isolation group and 108,007 +/- 31,532 IE in
      the failure group. Donor age was significantly younger in the success group (41.9
      +/- 4.0 years old in the success group vs. 57.5 +/- 2.2 years old in the failure
      group, p = 0.003). Chronic pancreatitis significantly decreased islet yields (p =
      0.006). Phase I time was significantly shorter (p = 0.010) and undigested tissue
      volume was significantly smaller (p = 0.020) in the success group. Purity was in
      positive correlation to postpurification islet yield, while donor age was in
      reverse correlation to postpurification islet yield. KIIM enables us to perform
      islet transplantation from NHBDs; however, the decision to use pancreata from
      older donors or those with chronic pancreatitis requires careful consideration.

PMID- 18819254
TI  - A novel human stem cell coculture system that maintains the survival and function
      of culture islet-like cell clusters.
AB  - Islet-like cell clusters (ICCs) have been suggested to be a source of insulin
      producing tissue for xenotransplantation in type 1 diabetes. We designed an
      approach to maintain the cultured rat pancreatic ICC survival and function, when
      cocultured with human umbilical cord mesenchymal stem cells (HUMSCs). HUMSCs in
      coculture have the ability to maintain ICC survival and function, for which
      number and insulin secretion of ICCs are increasing and lasting for 3 months,
      while ICCs gradually crash, which results in cell death after a period of 12 days
      of culture without HUMSCs. Cytokine protein array showed it has more than a
      twofold increase in levels of several cytokines (interleukin-6, tissue inhibitor
      of metalloproteinases-1, tissue inhibitor of metalloproteinases-2, monocyte
      chemoattractant protein-1, growth related oncogene, hepatocyte growth factor,
      insulin-like growth factor binding proteins 4, and interleukin-8) on coculture
      medium, implying an important role of these cytokines in this coculture system.
      These findings suggest that coculture with HUMSCs may have a significant
      potential to protect ICCs from damage during culture, and may be employed in a
      novel culture approach to maintain islet cell survival and function before
      transplantation.

PMID- 18819255
TI  - Cochlear repair by transplantation of human cord blood CD133+ cells to nod-scid
      mice made deaf with kanamycin and noise.
AB  - We investigated the fate of human cord blood CD133+ hematopoietic stem cells
      (HSC) transplanted intravenously (IV) into irradiated nod-scid mice previously
      made deaf by ototoxic treatment with kanamycin and/ or intense noise, to verify
      whether HSC engraft the cochlea and contribute to inner ear restoration, in vivo.
      We tested the presence of HLA.DQalpha1 by PCR, used for traceability of engrafted
      cells, finding evidence that HSC migrated to various host tissues, including the
      organ of Corti (OC). By histology, antibody and lectin-staining analysis, we
      confirmed that HSC IV transplantation in mice previously damaged by ototoxic
      agents correlated with the repair process and stimulation ex novo of
      morphological recovery in the inner ear, while the cochlea of control oto
      injured, nontransplanted mice remained seriously damaged. Dual color FISH
      analysis also provided evidence of positive engraftment in the inner ear and in
      various mouse tissues, also revealing small numbers of heterokaryons, probably
      derived from fusion of donor with endogenous cells, for up to 2 months following
      transplantation. These observations offer the first evidence that transplanted
      human HSC migrating to the inner ear of oto-injured mice may provide conditions
      for the resumption of deafened cochlea, emerging as a potential strategy for
      inner ear rehabilitation.

PMID- 18819256
TI  - Different cardiovascular potential of adult- and fetal-type mesenchymal stem
      cells in a rat model of heart cryoinjury.
AB  - Efficacy of adult (bone marrow, BM) versus fetal (amniotic fluid, AF) mesenchymal
      stem cells (MSCs) to replenish damaged rat heart tissues with new cardiovascular
      cells has not yet been established. We investigated on the differentiation
      potential of these two rat MSC populations in vitro and in a model of acute
      necrotizing injury (ANI) induced by cryoinjury. Isolated BM-MSCs and AF-MSCs were
      characterized by flow cytometry and cytocentrifugation and their potential for
      osteogenic, adipogenic, and cardiovascular differentiation assayed in vitro using
      specific induction media. The left anterior ventricular wall of syngeneic Fisher
      344 (n = 48) and athymic nude (rNu) rats (n = 6) was subjected to a limited,
      nontransmural epicardial ANI in the approximately one third of wall thickness
      without significant hemodynamic effects. The time window for in situ stem cell
      transplantation was established at day 7 postinjury. Fluorochrome (CMTMR)-labeled
      BM-MSCs (2 x 10(6)) or AF-MSCs (2 x 10(6)) were injected in syngeneic animals (n
      = 26) around the myocardial lesion via echocardiographic guidance. Reliability of
      CMTMR cell tracking in this context was ascertained by transplanting genetically
      labeled BM-MSCs or AF-MSCs, expressing the green fluorescent protein (GFP), in
      rNu rats with ANI. Comparison between the two methods of cell tracking 30 days
      after cell transplantation gave slightly different values (1420,58 +/- 129,65
      cells/mm2 for CMTMR labeling and 1613.18 +/- 643.84 cells/mm2 for genetic
      labeling; p = NS). One day after transplantation about one half CMTMR-labeled AF
      MSCs engrafted to the injured heart (778.61 +/- 156.28 cells/mm2) in comparison
      with BM-MSCs (1434.50 +/- 173.80 cells/mm2, p < 0.01). Conversely, 30 days after
      cell transplantation survived MSCs were similar: 1275.26 +/- 74.51/mm2 (AF-MSCs)
      versus 1420.58 +/- 129.65/mm2 for BM-MSCs (p = NS). Apparent survival gain of AF
      MSCs between the two time periods was motivated by the cell proliferation rate
      calculated at day 30, which was lower for BM-MSCs (6.79 +/- 0.48) than AF-MSCs
      (10.83 +/- 3.50; p < 0.01), in the face of a similar apoptotic index (4.68 +/-
      0.20 for BM-MSCs and 4.16 +/- 0.58 for AF-MSCs; p = NS). These cells were also
      studied for their expression of markers specific for endothelial cells (ECs),
      smooth muscle cells (SMCs), and cardiomyocytes (CMs) using von Willebrand factor
      (vWf), smooth muscle (SM) alpha-actin, and cardiac troponin T, respectively.
      Grafted BM-MSCs or AF-MSCs were found as single cell/small cell clusters or
      incorporated in the wall of microvessels. A larger number of ECs (227.27 +/-
      18.91 vs. 150.36 +/- 24.08 cells/mm2, p < 0.01) and CMs (417.91 +/- 100.95 vs.
      237.43 +/- 79.99 cells/mm2, p < 0.01) originated from AF-MSCs than from BM-MSCs.
      Almost no SMCs were seen with AF-MSCs, in comparison to BM-MSCs (98.03 +/- 40.84
      cells/mm2), in concordance with lacking of arterioles, which, instead, were well
      expressed with BM-MSCs (71.30 +/- 55.66 blood vessels/mm2). The number of
      structurally organized capillaries was slightly different with the two MSCs
      (122.49 +/- 17.37/mm2 for AF-MSCs vs. 148.69 +/- 54.41/mm2 for BM-MSCs; p = NS).
      Collectively, these results suggest that, in the presence of the same postinjury
      microenvironment, the two MSC populations from different sources are able to
      activate distinct differentiation programs that potentially can bring about a
      myocardial-capillary or myocardial-capillary-arteriole reconstitution.

PMID- 18819257
TI  - Myocardial repair achieved by the intramyocardial implantation of adult
      cardiomyocytes in combination with bone marrow cells.
AB  - Various cytokines produced by bone marrow cells can protect adult cardiomyocytes
      against apoptosis. Thus, we investigated the feasibility of implanting adult
      cardiomyocytes in combination with bone marrow cells for myocardial repair.
      Ventricular cardiomyocytes were isolated from adult rats and cocultured with bone
      marrow cells. Using a rat model of doxorubicin-induced cardiomyopathy, we
      injected 6 x 10(5) adult cardiomyocytes, 3 x 10(7) bone marrow cells, or both
      into damaged hearts, for myocardial repair. Coculture of the cardiomyocytes with
      the bone marrow cells enhanced the expression of integrin-beta1D and focal
      adhesion kinase in cardiomyocytes, resulting in increased survival and decreased
      apoptosis of the cardiomyocytes after 7 days of culture. Compared with the
      baseline levels, cardiac function was preserved by the implantation of bone
      marrow cells alone and by the implantation of cardiomyocytes in combination with
      bone marrow cells, but it was decreased significantly 28 days after the
      implantation of cardiomyocytes alone. Furthermore, apoptosis of the host
      cardiomyocytes was decreased significantly after the implantation of bone marrow
      cells alone, or in combination with cardiomyocytes, compared with that after the
      implantation of cardiomyocytes alone (p < 0.01). Interestingly, the implantation
      of adult cardiomyocytes in combination with bone marrow cells resulted in a
      dramatic increase in the survival of donor cardiomyocytes, and induced the
      myogenic differentiation of donor bone marrow stem cells. Our findings indicate
      that cardiomyocytes and bone marrow cells can assist and compliment each other;
      thus, the implantation of adult cardiomyocytes in combination with bone marrow
      cells shows promise as a feasible new strategy for myocardial repair.

PMID- 18819258
TI  - In vivo survival and osteogenic differentiation of allogeneic rat bone marrow
      mesenchymal stem cells (MSCs).
AB  - Marrow mesenchymal stem cells (MSCs) are multipotent progenitor cells and
      reported to be immunoprivileged as well as immunosuppressive. Hence, MSCs might
      be ideal candidates for allogeneic transplantation to induce regeneration of
      damaged tissues/organs. To confirm the differentiation capability of allogeneic
      MSCs in vivo is important for the acceleration of regenerative medicine.
      Consequently, we have established an in vivo rat model using subcutaneous
      implantation of a hydroxyapatite (HA) ceramic/MSCs composite. Osteogenic
      differentiation was used as an indicator of differentiation. When syngeneic MSCs
      were implanted, MSCs showed osteogenic differentiation as evidenced by new bone
      formation as well as high alkaline phosphatase (ALP) activity. When allogeneic
      MSCs were implanted, none of the allografts survived or showed osteogenic
      differentiation. However, when the recipient rats were treated with FK506
      immunosuppressant, allogeneic MSCs showed osteogenic differentiation. Although
      this finding might not be adequate for the acceleration of regenerative medicine,
      these results did confirm that MSCs are not intrinsically immunoprivileged but
      that under appropriate immunosuppressant treatment, allogeneic MSCs can survive
      and show differentiation capability in vivo.

PMID- 18819259
TI  - IL-10 and IL-4 in skin allograft survival induced by T-cell depletion plus
      deoxyspergualin.
AB  - The mechanisms mediating T-cell depletion plus 15-deoxyspergualin (DSG)-induced
      prolonged allograft survival or tolerance are uncertain. The purpose of this
      study is to evaluate the role of IL-4 and IL-10 in prolonged allograft survival
      induced by T-cell depletion plus DSG. MHC mismatched skin allograft
      transplantation was performed, using wild-type and three separate knockout (i.e.,
      IL-4-/-, Stat6-/-, or IL-1-/ -) mice as recipients. Induction therapy consisted
      of T-cell depletion and or brief course of DSG. The data demonstrate that
      monotherapy with T-cell-depleting mAbs or DSG prolonged skin allograft survival,
      compared to controls, in wild-type Balb/c recipients [median survival time (MST)
      = 25 and 21 vs. 10 days, p < 0.007]. T-cell depletion plus DSG further augmented
      skin allograft survival in wild-type animals relative to monotherapy (MST = 35
      days vs. 25 and 21 days, p < 0.006 vs. mAbs or DSG only), and was equally
      effective in IL-4-/- and Stat6-/- recipients. In contrast, combined therapy was
      no better than monotherapy in IL-10-/- animals (p > 0.05). Furthermore, skin
      allograft survival after combined therapy was shorter in IL-10-/- versus wild
      type recipients (MST 20 and 41 days, respectively, p < 0.001). IL-4-mediated
      signaling through Stat6 is dispensable for prolonged allograft survival induced
      by T-cell depletion plus DSG. In contrast, IL-10 appears to be important for
      prolonged allograft survival induced by combined therapy in this model.

PMID- 18819260
TI  - Evaluation of attention-deficit/hyperactivity disorder symptoms in male children
      with high-functioning pervasive developmental disorders.
AB  - BACKGROUND: Although there are many reports of high rates of hyperactivity and
      attention deficits in children with Pervasive Developmental Disorders (PDD),
      controversy remains about the applicability of the diagnosis of Attention
      Deficit/Hyperactivity Disorder (ADHD) to PDD children. The present study
      elucidates the similarities and differences of ADHD symptoms in PDD children
      compared to ADHD children. METHODS: Twenty-seven male children with PDD+ADHD
      Combined type (ADHD-C), 17 males with ADHD-C, and 9 males with PDD without ADHD
      C, were compared on measures of ADHD symptoms and related behaviors using parent
      ratings and teacher ratings on the ADHD Rating Scale (ADHDRS), the Child Behavior
      Checklist (CBCL) and the Teacher Report Form (TRF). RESULTS: The PDD+ADHD-C and
      the ADHD-C groups had significantly higher ratings than the PDD only group for
      all the scores on both the parent-rated and the teacher-rated ADHDRS. The ADHD-C
      and PDD+ADHD-C groups had significantly higher scores than the PDD group on
      Delinquent Behavior, Aggressive Behavior, and Externalizing Behavior of the CBCL
      and on Delinquent Behavior of the TRF; there were no significant differences
      between the ADHD-C and PDD+ADHD-C groups on any scores of the CBCL and TRF.
      CONCLUSIONS: The PDD+ADHD-C and ADHD-C groups share a similar profile of ADHD
      symptoms and externalizing behaviors, and the comorbidity of ADHD and PDD should
      be suspected when ADHD symptoms are present in PDD children.

PMID- 18819261
TI  - The effects of nifekalant hydrochloride on the QT dispersion after direct-current
      defibrillation.
AB  - BACKGROUND: Although nifekalant hydrochloride (NIFE) has been demonstrated to
      suppress ventricular tachyarrhythmia, especially electrical storm, the mechanism
      by which it does so is still unclear. We examined its effects on the spatial
      dispersion of repolarization (SDR) after implantable cardioverter-defibrillator
      (ICD) shock. METHODS AND RESULTS: In twenty five patients with an ICD, we
      recorded the 87-lead ECG during sinus rhythm (the CONTROL group) under general
      anesthesia, after NIFE administration alone, and just after termination of
      induced ventricular fibrillation (VF) by ICD shock with or without NIFE
      administration. In all recordings, the corrected QT interval (QTc) was measured
      in each lead. The dispersion of QTc (QTc-D; maximum QTc minus minimum QTc) was
      also measured. Compared with the CONTROL, the QTc-D exhibited significant
      deterioration after ICD shock (61 +/- 12, 91 +/- 24 ms(1/2), respectively, p <
      0.001). However, the QTc-D after NIFE administration either with or without ICD
      shock did not differ from the CONTROL group (65 +/- 20, 61 +/- 18, and 61 +/- 12
      ms(1/2), respectively, p = 0.99). CONCLUSIONS: NIFE suppressed the deterioration
      of SDR by ICD shock. This might be a mechanism by which NIFE suppresses
      recurrence of ventricular tachyarrhythmia after ICD shock.

PMID- 18819262
TI  - Long-term cardiovascular outcomes following ischemic heart disease in patients
      with and without peripheral vascular disease.
AB  - BACKGROUND: Peripheral vascular disease (PVD) is associated with an increased
      risk of cardiovascular disease. However, few studies have evaluated the prognosis
      of asymptomatic PVD in patients with coronary artery disease (CAD). METHODS: The
      aim of the study was to determine the prevalence of asymptomatic and symptomatic
      PVD in patients with ST-elevated myocardial infarction (STEMI) or unstable angina
      pectoris (UAP) who underwent percutaneous coronary intervention (PCI), and to
      conduct a 3-year follow-up for cardiovascular events. Systemic atherosclerosis
      was evaluated, using duplex ultrasonography in 380 consecutive patients who had
      undergone PCI from January 2003 to December 2005. RESULTS: Twenty-four percent of
      the CAD patients had PVD. Patients with PVD had significantly more risk factors
      for atherosclerosis, including increased age, diabetes mellitus, smoking (p <
      0.05), and multivessel CAD (p < 0.001). Multivariate regression analysis
      demonstrated that STEMI, PVD and multivessel CAD were independent predictors for
      major adverse cardiac events (MACE) (p < 0.05). Kaplan-Meier curves for MACE in
      all the patients showed that the MACE rates were significantly higher in STEMI
      and PVD cases compared with other cases (p < 0.05). We also classified patients
      with PVD into symptomatic (53%) and asymptomatic (47%) cases, and the MACE rates
      between these groups did not differ significantly (p < 0.82). CONCLUSIONS: There
      is a high prevalence of asymptomatic PVD in patients with CAD and even
      asymptomatic PVD is associated with increased CAD mortality.

PMID- 18819263
TI  - Impact of body mass index and Framingham risk score on coronary artery plaque.
AB  - BACKGROUND: It is still unclear whether traditional risk factors for heart
      disease and body weight correlate with the progression of left main coronary
      artery (LMCA) atherosclerosis. Thus, the aim of this study was to evaluate the
      cross-sectional relation between conventional risk score or metabolic disorder
      and non-stenotic LMCA atherosclerosis using intravascular ultrasound (IVUS).
      METHODS: We analyzed procedural and demographic data from 217 consecutive
      patients undergoing intervention for a left anterior descending or left
      circumflex coronary artery lesion, including their cardiovascular risk
      (Framingham risk score) and degree of adiposity. IVUS measurements for
      subclinical LMCA plaque were obtained in all patients and compared to their risk
      score (low, intermediate or high risk [< or =10%, 10-20%, and > or =20%,
      respectively]), with volumetric IVUS analyses being performed for the entire
      LMCA. Patients were further stratified by body weight (normal vs
      overweight/obesity [body mass index > or =25 kg/m2]). RESULTS: Plaque volume
      index was greater in patients with high and intermediate risk groups compared to
      the low risk group (plaque volume index; 9.8 +/- 2.9 mm3/mm and 10.1 +/- 3.0
      mm3/mm vs. 8.3 +/- 2.7 mm3/mm, p=0.017 and p=0.0002, respectively). Plaque volume
      index was also greater in patients in the overweight/obesity group compared to
      the normal weight group (plaque volume index; 10.2 +/- 2.9 mm3/mm vs 9.1 +/- 3.0
      mm3/mm, p=0.005). Linear regression analysis identified overweight/obesity
      (p=0.034) and high 10-year CAD risk (p=0.003) as independent predictors of
      increased LMCA plaque volume index. CONCLUSIONS: Conventional coronary risk
      factors, as well as adiposity itself, related to the volume of coronary plaque at
      non-stenotic LMCA.

PMID- 18819264
TI  - Contralateral pneumothorax after lung cancer surgery: report of two cases.
AB  - Due to recent increases in numbers of patients who underwent surgical treatments
      for lung cancer, numbers of complications of contralateral pneumothorax after
      lung surgery are suggested to increase. Moreover, recent spread of surgical
      indication to elderly people and patients with severely damaged pulmonary
      function may lead postoperative complication of contralateral pneumothorax more
      lethal. We herein describe 2 cases of contralateral pneumothorax following lung
      cancer surgery with a review of recent literatures. Case 1 underwent left lower
      lobectomy with combined partial resection of the chest wall for lung cancer. Five
      months later, he suffered from contralateral pneumothorax and respiratory
      failure. Immediate chest drainage followed by bullectomy and pleurodesis were
      performed. Case 2 was surgically treated for left lung cancer. Preoperative
      computed tomography incidentally demonstrated contralateral pneumothorax. Chest
      drainage was started immediately, followed by left lower lobectomy. Contralateral
      bullectomy and pleurodesis were performed 6 days after lobectomy. Both patients
      have been well without recurrence of pneumothorax or lung cancer.

PMID- 18819265
TI  - Focal fatty change in the medial segment of the liver occurring after
      gastrectomy: report of a case.
AB  - A 70-year-old Japanese man underwent distal gastrectomy for gastric cancer.
      Preoperative computed tomography detected no tumor in the liver. Six months after
      the operation, ultrasound examination revealed a hyperechoic mass, measuring 3 cm
      in diameter, in the medial segment of the liver. Dynamic computed tomography of
      the liver also revealed that low-density area with mosaic enhancement in the
      dorsal portion of the medial segment. Assay for hepatitis B surface antigen was
      positive. Levels of carcinoembryonic antigen and alpha-fetoprotein were normal.
      Computed tomography during arterial portography revealed a perfusion defect in
      the area corresponding to the mass lesion. Although laparotomy was performed, no
      abnormality was found in the dorsal portion of the medial segment on inspection
      and palpation during surgery. We therefore performed incisional biopsy and frozen
      histologic examination, which revealed fatty deposition in the hepatic parenchyma
      and no evidence of malignancy. Finally, histologic examination made a diagnosis
      of macrovesicular steatosis surrounded by normal liver parenchyma.

PMID- 18819266
TI  - [A new approach to estimating the significance of identification of deletion
      inserts in pairwise alignment].
AB  - Within the framework of the unique method of estimating the significance of
      pairwise alignment of nucleotide sequences, developed by the authors, a new
      approach to the analysis of deletion inserts in pairwise alignment has been
      realized. It was shown that the decrease in the average integral length of
      deletion inserts in alignments obtained using the modern algorithms, as compared
      with true alignments, is related to a decrease in the number of some deletion
      inserts rather than a decrease in their average length.

PMID- 18819267
TI  - [How electronic interference can be applied in the research of the structure of
      small bioobjects and for "fast reading" of nucleotide sequences].
AB  - A method for the study of the surface of small bioobjects, such as macromolecules
      and their complexes has been developed. The method is based on the phenomenon of
      the interference of low-energy electrons. Using the interference, it is possible
      to construct analogues of holograms for these bioobjects but, as distinct from
      optical holography, with the spatial restriction at the level of internuclear
      distances. The method enables one to obtain a set of holograms at different
      energies of electrons. The information thus obtained can suffice to determine the
      type of molecular groups located on the suffice of the object being examined. The
      method can be used, e.g., for the "fast reading" of genetic texts.

PMID- 18819268
TI  - [Effects of hydrophilic and hydrophobic hydration in tetramethylbisurea and N,N'
      dimethylpropyleneurea solutions].
AB  - The thermal effects of dissolving tetramethylbisurea in water at 298-318 K and
      N,N'-dimethylpropyleneurea at 293-313 K have been measured. It was shown that the
      standard heat of dissolution of tetramethylbisurea at 298 K was 3.58 +/- 0.04
      kJ/mol, and that of N,N'-dimethylpropyleneurea was 22.8 +/- 0.01 kJ/mol. The
      standard heat capacities of urea derivatives at 298 K differed insignificantly:
      167 +/- 10 J/(mol x K) and 149 +/- 5 J/(mol x K) for tetramethylbisurea and N,N'
      dimethylpropyleneurea, respectively, indicating the moderately hydrophobic
      character of hydration of these compounds. It was found that, at temperatures
      close to the temperature of maximum density of water (277 K), the temperature
      dependence of Gibbs energy for tetramethylbisurea goes through the maximum.

PMID- 18819269
TI  - [Molecular dynamics of oligopeptides. A comparative study of the interactions of
      amino acid residues in dipeptide structures].
AB  - A comparative study of the molecular dynamics of dipeptides consisting of natural
      amino acid residues has been carried out. Molecular dynamics protocols were used
      that do not violate the principle of equidistribution of energy by degrees of
      freedom. Autocorrelation functions of complex exponential curves from dihedrals
      were used for the comparative analysis. The interactions of amino acid residues
      were classified by their influence on the dynamic properties of neighboring amino
      acid residues.

PMID- 18819270
TI  - [Short fragments of a protein globule with predominant conformation].
AB  - It has been found that 1500 tetrapeptides out of 160000 possible combinations
      occurring in proteins exhibit preference for particular conformational states.
      Most conformationally stable tetrapeptides obtained in the analysis of a sampling
      containing 706 proteins are in the alpha-helical form. The features of the amino
      acid composition of conformationally stable oligopeptides have been studied.

PMID- 18819271
TI  - [The mechanism of oxymyoglobin oxidation by copper ions and complexes: myoglobins
      carboxymethylated and carboxyamidated at histidine residues].
AB  - The oxidation of sperm whale oxymyoglobin (MbO2) and its chemically modified
      derivatives alkylated at solvent-accessible histidines by sodium bromoacetate (CM
      MbO2) and iodoacetamide (CA-MbO2) in the presence of ions and glycine complexes
      of copper, Cu2+, Cu(Gly)+, and Cu(Gly)2, has been studied. The influence of the
      reagent concentration, pH, and ionic strenth of medium, and also of competitive
      redox-inactive zinc ions on the reaction was investigated. The localization of
      Cu(Gly)2 in native sperm whale met-Mb and CM-met-Mb was examined by the high
      resolution NMR method. The data obtained confirm that the linkage of copper
      compounds to surface histidines (all of them are away from the heme, at a
      distance of 1.8-2.7 nm) has only a minor (no more than 35%) contribution to the
      overall reaction rate, in particular under conditions of a large, more than 8-10
      fold, data, excess of the reagent. The noticeable contribution of His116(113),
      His48, and His81, which according to NMR are localized on the protein surface and
      have the greatest affinity to copper, is revealed only at small concentrations of
      copper, a less than 5-fold excess relative to the protein. This is supported by
      the sigmoidal pH-dependence curve with the transition pK 6.5 at the equimolar
      copper concentration. The main contribution to the rate of the reaction studied
      should involve a linkage of copper to internal histidines, His97(FG4), which is
      0.66 nm apart from the heme, and to distal His64(E7). Both are hydrogen bonded,
      the first with carboxyl group of one of the heme propionates, and the second with
      liganded O2, have a much lower affinity to copper than surface histidines, and
      are inaccessible to the modification.

PMID- 18819272
TI  - [A study of the effect of ceruloplasmin and lactoferrin on the chlorination
      activity of leukocytic myeloperoxidase using the chemiluminescence method].
AB  - The chlorination activity of free myeloperoxidase and myeloperoxidase bound with
      ceruloplasmin or with both ceruloplasmin and lactoferrin has been studied by
      luminal-dependent chemiluminescence. It was shown that the addition of hydrogen
      peroxide to the "myeloperoxidase + Cl- + luminal" system is accompanied by a fast
      flash of light emission. In the absence of myeloperoxidase or Cl-, the flash
      intensity was considerably reduced. The inhibitor of myeloperoxidase NaN3, the
      HOCl scavengers taurine and methionine, and guaiacol, a substrate for
      peroxidation cycle of myeloperoxidase, prevented luminescence. These results
      suggest that the generation of luminescence was due to the halogenating activity
      of myeloperoxidase, and hence, the flash light sum may serve as a measure of
      chlorination activity of myeloperoxidase. The activity of myeloperoxidase was
      suppressed by ceruloplasmin. Lactoferrin exhibited no significant influence on
      the myeloperoxidase activity, nor did it prevent the inhibitory effect of
      ceruloplasmin when they both were combined with myeloperoxidase. These data were
      confirmed using alternative approaches for evaluating the myeloperoxidase
      activity, namely, the assessment of peroxidation activity and the taurine
      chlorination assay. It is noteworthy that the inhibitory effect of ceruloplasmin
      on chlorination and peroxidation activities of myeloperoxidase is seen with the
      latter, traditional approaches only if ceruloplasmin is present in a large excess
      relative to myeloperoxidase, whereas the chemiluminescence method allows the
      detection of the inhibitory effect of ceruloplasmin using lower proportions of
      the protein with respect to myeloperoxidase, which are close to the stoichiometry
      of the myeloperoxidase/ceruloplasmin and the
      myeloperoxidase'ceruloplasmin'lactoferrin complexes.

PMID- 18819273
TI  - [Investigation of the mechanisms of crystallin aggregation induced by pulsed
      laser UV irradiation at 308 nm].
AB  - The results of the investigations of photoaggregation of the main eye lens
      proteins alpha-, beta- and gamma-crystallins and the model protein carbonic
      anhydrase in response to pulsed irradiation by a XeCI laser at 308 nm in the wide
      range of pulse energy densities (w) and pulse repetition rates (F) have been
      reviewed. A nonlinear dependence of aggregation efficiency on the values of w, F,
      and the concentration of protein solution was found. A theoretical model that
      qualitatively describes the experimental results was developed. The aggregation
      of N-amino-arm truncated beta A3-crystallin was analyzed. It was found that the
      loss of the N-amino-arm as a result of mutation or eye lens aging increases the
      probability of UV-induced beta-crystallin aggregation, thereby increasing the
      predisposition of eye lens to senile cataract. The influence of some short-chain
      peptides on the aggregation efficiency of beta-crystallin and beta-crystallin in
      solution with alpha-crystallin was investigated. Based on the results obtained, a
      combination of peptides (called "a new preparation") was found that most
      effectively delays the crystallin aggregation. The preparation has been probed on
      experimental animals. The trials showed that the preparation increases the delay
      in the development of UV-induced cataract in rats. The possibility of designing a
      drug for the prophylaxis of the development of cataract in humans based on this
      preparation is discussed.

PMID- 18819274
TI  - [Influence of lipids on ice formation during the freezing of cryoprotective
      medium].
AB  - The influence of lipids on ice formation during the freezing of cryoprotective
      medium for the semen of rainbow trout has been studied by the cryomicroscopy
      technique. It was shown that the lipids extracted from marine vertebrates and
      liposomes from the lipids of trout sperm effectively inhibit the ice formation in
      cryoprotective solutions during freezing, fundamentally changing the form and
      size of ice crystals. At high concentrations of lipids, either the
      crystallization does not occur in the cryoprotective medium or, even if ice
      crystals are formed, they have a broken shape and blurred borders. The addition
      of egg yolk sligthly increases the size and essentially changes the shape of ice
      crystals during the freezing of solution.

PMID- 18819275
TI  - [Phosphorescent analysis of the action of detergents on the internal dynamics of
      membrane proteins of human erythrocytes].
AB  - The slow (millisecond) internal dynamics of proteins isolated from human
      erythrocyte membranes under the action of ionic and nonionic detergents: sodium
      dodecyl sulfate (0.1-6 mM), sodium deoxycholate (0.16-6 MM), N-Lauroylsarcosine
      Na+-salt (Sarkosyl) (0.17-6 mM), digitonin (0.025-6 MM), and Tween-20 (0.01-6 mM)
      has been studied by the method of room-temperature tryptophan phosphorescence. It
      has been established that the destruction of protein ensembles, the disturbance
      of protein-lipid interactions, and the unfolding of proteins in membrane result
      in a considerable increase of slow intramolecular dynamics of proteins. The
      effects of detergents on the structural and dynamical state of membrane proteins
      differ depending on their chemical features. On the bases of the results
      obtained, it has been concluded that the low internal dynamics of membrane
      proteins in situ, compared with most soluble proteins, is due to the presence of
      protein ensembles in membrane, the isolation of macromolecules from the aqueous
      surroundings by the lipid bilayer, and a high content of alpha-helices and beta
      sheets in macromolecules.

PMID- 18819276
TI  - [Dynamics of active transmembrane ion transfer in transport enzymes].
AB  - It has been shown that recent investigations of the electron density distribution
      and high resolution (approximately 0.5 nm) spatial structure of transport ATPases
      open new possibilities in the development of general models for the mechanisms of
      energy of ATP hydrolysis and its use for active transmembrane ion transfer.

PMID- 18819277
TI  - [Temperature dependence of the acetylcholinesterase activity in synaptic
      membranes of the rat brain].
AB  - The temperature dependence (5-40 degrees C) of the acetylcholinesterase activity
      in synaptic membranes of the rat brain at different substrate concentrations was
      studied. At low substrate concentrations, the Arrhenius plot has two linear
      sections. At high concentration, there is one linear section throughout the
      temperature range. The addition of glycerol to incubation medium to final
      concentrations of 1 and 2% (w/v) increases the Michaelis constant, without
      affecting the maximal rate and the inhibition constant. The role of diffusion in
      the temperature dependence of the acetylcholinesterase activity is discussed.

PMID- 18819278
TI  - [Quantitative characteristic of the redox state of erythrocytes].
AB  - The introduction of the parameters characterizing the redox state of the cell,
      such as the effective redox potential and the redox buffer capacity has been
      theoretically substantiated. A comparative study of the parameters of the redox
      state of erythrocytes from healthy donors and patients with diabetes and acute
      coronary syndrome has been performed. It was found that the redox buffer capacity
      in erythrocytes from patients with diabetes and acute coronary syndrome was
      reduced by 30-40% in comparison with the redox buffer capacity of erythrocytes
      from healthy donors. The largest change in the effective redox potential was
      observed for erythrocytes from patients with diabetes, which indicates a more
      expressed oxidative stress in this pathology.

PMID- 18819279
TI  - [On the electron stabilization within the quinone acceptor part of Rhodobacter
      sphaeroides photosynthetic reaction centers].
AB  - The time evolution of the photoinduced differential absorption spectrum of
      isolated Rhodobacter sphaeroides photosynthetic reaction centers was
      investigated. The measurements were carried out in the spectral region of 400-500
      nm on the time scale of up to 200 microseconds. The spectral changes observed can
      be interpreted in terms of the effects of proton shift along hydrogen bonds
      between the primary quinone acceptor and the protein. A theoretical analysis of
      the spectrum time evolution was performed, which is based on the consideration of
      the kinetics of proton tunneling along the hydrogen bond. It was shown that the
      stabilization of the primary quinone electronic state occurs within the first
      several tens of microseconds after quinone reduction. It slows down upon the
      deuteration of reaction centers as well as after adding 90% of glycerol; on the
      other hand, it accelerates as temperature rises up to 40 degrees C.

PMID- 18819280
TI  - [Analysis of the temporal organization of the synthesis of RNA and protein in
      blood lymphocytes during the immune response of the body].
AB  - The temporal organization of the synthesis of RNA and antibodies in
      immunocompetent cells has been investigated by fluorecsent spectroscopy. Two
      fluorochromes: acridine orange and 1-anilino-8-naphthalenesulfonate were used.
      Temporal changes in the mean values of the characteristic parameters alpha' and
      beta in blood lymphocytes stained with acridine orange and 1-anilino-8
      naphthalenesulfonate in the immune reaction to the introduction of ovalbumin were
      obtained. It was shown that the maximal increase in RNA and protein synthesis in
      blood lymphocytes by a factor of 6-8 occurs after the fourth immunization. The
      simultaneous increase in RNA and protein synthesis in cells was indicative of
      cell activation. A general response of immunocompetent blood cells to the
      introduction of the antigen was observed. The results confirm the idea about the
      cooperative interaction between different lymphocyte subpopulations during the
      synthesis of antibodies.

PMID- 18819281
TI  - [Mathematical modeling of the evolution of bacterial populations in continuous
      cultures with regard to the nonmutagenic variability of genome].
AB  - A mathematical model of the evolution of the genetic structure of the bacterial
      population during prolonged cultivation in a chemostat has been constructed. In
      addition to genetic mutations, some factors of the nonmutagenic variability of
      genome were taken into account, namely, the structural reorganization of plasmid
      and virus DNA, the DNA loss due to cellular division, the conjugative transfer of
      plasmids, and the plasmid replication. The general model also takes into account
      the formation of cellular aggregates during conjugation. The results of numerical
      and analytical investigation of the special cases of the general model were
      treated. Simplified mathematical models are considered, which can be used to
      explain the experimentally observed evolutionary variations resulting from the
      plurality of evolution attractors, multi-stage microevolutionary transitions, the
      semi-stable states of the bacterial population genome, and the undamped
      oscillations of the genetic structure of the population during prolonged
      cultivation in the chemostat.

PMID- 18819282
TI  - [Effect of the stem cell factor on the morphology and functional state of mouse
      embryonic stem cells].
AB  - The effect of the stem cell factor on the state of membranes and functional
      activity of mouse embryonic stem cells cultivated in LIF (Leukemia Inhibitory
      Factor) cytokine-free and LIF-containing media has been studied. It was shown
      that the stem cell factor induces changes in the viscosity of membrane lipid
      bilayer and increases the respiration rate, the ATP level, and the proliferation
      activity of embryonic stem cells. An intricate character of the LIF-dependent
      modification of biological effects of the stem cell factor was revealed.

PMID- 18819283
TI  - [Immobilization of Saccharomyces yeast cells on electret polyethylene films].
AB  - The method of electret-thermal analysis developed in dielectric physics has been
      applied to monitor bioelectric phenomena that accompany the immobilization of
      microorganisms on electret substrates. A spectrum of thermo stimulated currents
      for biofilms consisting of immobilized Saccharomyces cells has been obtained. The
      spectrum represents a halo in the region of 30-90 degrees C. The immobilization
      of Saccharomyces cells on electret polyethylene films results in their
      depolarization that is recorded on the spectra of thermostimulated currents as a
      reduction of the current peak corresponding to the polyethylene melting point. A
      hypothesis has been put forward that explains the phenomenon by the absorption of
      the electric energy of polarized substrates by the cells for the occurrence of
      metabolic reactions.

PMID- 18819284
TI  - [Changes in the lipid composition of embryonic cells of the mussel Mytilus
      trossulus during cryopreservation].
AB  - A comparative analysis of the lipid composition of embryonic cells of the mussel
      Mytilus trossulus prior to, and after, cryopreservation in liquid nitrogen was
      carried out in the presence of two types of cryoprotectors: 1) dimethylsulfoxide
      and trehalose; and 2) dimethylsulfoxide, trehalose, total lipid extract from the
      mussel Crenomytilus grayanus, alpha-tocopherol and ascorbic acid. It was found
      that not only the cell viability but also the fatty acid composition of cell
      lipids after cryopreservation depend on the composition of cryoprotectors used.
      The content of saturated fatty acids, monoenic and polyenic fatty acids, the
      omega 3/omega 6 ratio, and the index of nonsaturation in the fatty acid
      composition of lipids was shown to change remarkably after cryopreservation.
      Possible reasons of these changes are discussed.

PMID- 18819285
TI  - [Dehydration in the cryopreservation of moist plant tissues and in seed
      maturation].
AB  - The possibility of long-term cryopreservation of plant objects depends on their
      water content. In orthodox seeds, it decreases at the late stage of maturation
      and is accompanied by the synthesis of protectors--sugars and proteins. These
      seeds easily withstand cryopreservation. Organs with a high water content,
      meristems, and recalcitrant seeds are dried in presence of sucrose before
      plunging in liquid nitrogen. In orthodox seeds, artificially dried moist seeds,
      and meristems, the cellular content forms glass structures that are estimated in
      frozen materials by differential scanning calorimetry and electron paramagnetic
      resonance methods. It is proposed that the glass cellular content is connected
      with the duration of cryopreservation. Methodical approaches to successive
      cryopreservation of moist plant tissues are described.

PMID- 18819286
TI  - [Influence of propagating electrical signals on delayed luminescence of geranium
      leaves. II. Theoretical analysis].
AB  - A mathematical model of delayed luminescence was devised. It is based on the
      description of primary photosynthetic reactions, which takes the donor and
      acceptor parties of photosystem II and the electrochemical gradient on thylakoid
      membranes into account. The model was used for the theoretical analysis of the
      mechanisms of changes in delayed luminescence characteristics, induced by
      variation potentials.

PMID- 18819287
TI  - [The relationship between the production of nitric oxide and the injury of
      cardiomyocytes caused by in vivo rat regional myocardial ischemia and
      reperfusion].
AB  - Changes in nitric oxide concentration in rat myocardium in vivo during temporary
      occlusion of the anterior descending coronary artery, followed by reperfusion
      were studied by microdialysis assay in risk and intact areas by using an NO spin
      trap (complex of ferrous ions with N-methyl-D, L-glucamine dihiocarbamate, Fe3+
      MGD2). The amplitude of the EPR signal of the NO spin adduct NO-Fe2+-MGD2 in the
      risk area increased during the 40-min occlusion and remained higher than the
      initial level during 60-min postischemic reperfusion, indicating a substantial
      nitric oxide production. The size of the infarction in the risk area by the end
      of reperfusion was 47 +/- 3 %, the contents of ATP, phosphocreatine, and total
      creatine decreased to 44 +/- 4, 51 +/- 5, and 60 +/- 3 %, correspondingly, as
      compared with initial values, and the level of lactate was six times higher than
      the initial one. In the intact area of the left ventricle, the level of nitric
      oxide and high-energy metabolites did not change throughout the experiment. It
      was shown that the intensive nitric oxide production, in acute regional ischemia
      and reperfusion are related to the disturbance of energy metabolism, the damage
      to cytoplasmic membranes, and the death of cardiomyocytes.

PMID- 18819288
TI  - [Role of water channels in the regulation of the volume of principal cells of rat
      kidney collecting ducts in hypoosmotic medium].
AB  - The effect of plasma membrane water permeability on the rate of changes in the
      volume of principal cells of collecting ducts of the outer substantia medullaris
      under conditions of hypoosmotic shock has been studied. Changes in cell volume
      were studied by the fluorescent method. It was shown that the hypotonic shock
      induced a rapid increase in the cell volume with the characteristic time that
      depended on plasma membrane water permeability. The decrease in volume occurred
      much more slowly, and the rate of volume decrease directly correlated with the
      rate of swelling. The inhibition of potassium transport by barium chloride
      decreased the rate of volume restoration, without affecting substantially the
      duration of the swelling phase. The inhibition of mercury-sensitive water
      channels by mercury caused a significant increase in the time of both cell
      swelling and volume restoration. It was concluded that the state of water
      channels largely determines the rate of the regulatory response of epithelial
      cells of collecting ducts to hypoosmotic shock and affects the exchange of cell
      osmolites.

PMID- 18819289
TI  - [Ultrasound-induced myocardial preconditioning: analysis of its effectiveness and
      mechanisms].
AB  - It has been shown that exposure of the isolated rat heart perfused according to
      Langendorff to therapeutic ultrasound (210 kHz and 0.5-1.5 W/cm2 ) induces a
      cardioprotective response similar to ischemic preconditioning. This reduces the
      infarct size and improves the postischemic systolic and diastolic function. The
      ATP-sensitive K+ channel blocker glybenclamide abolished the protection afforded
      by ultrasound; in contrast, the free radical scavenger N-2-MPG did not influence
      the ultrasound-induced cardioprotective response.

PMID- 18819290
TI  - [Adaptation of interacting populations to the environmental temperature regime].
AB  - The biological process of the passing of individuals from the active to the
      passive state when unfavourable environmental conditions occur has been
      formalized. This leads to a universal linear superstructing to nonlinear models
      of ecosystems. At certain rates of this jump, a stabilization of the oscillation
      instability is possible, and an increase in population vitality can occur. The
      adaptation processes were examined, and the areas of evolutionarily stable
      parameters for interacting population (competitors and antagonists) on regular
      temperature changes were found. A possibility of cyclic changes of parameters in
      the "prey-predator" system was shown.

PMID- 18819291
TI  - [Influence of "zero" magnetic field on the growth of embryonic cells and primary
      embryos of mouse in vitro].
AB  - The present investigation reveals that a 250-fold screening of the geomagnetic
      field ("zero" geomagnetic fields, 200 nT) is a biologically active factor that
      adversely affects embryonic cells and the processes of early embryogenesis as a
      whole. In particular, the cultivation of primary embryonic fibroblasts in "zero"
      geomagnetic fields causes reduces the capacity for adhesion and proliferation,
      changes the monolayer morphology and increases cell death. In a more highly
      organized experimental model, two-celled mouse embryos, the exposure to the
      "zero" field results in an increase of plasma membrane permeability for dyes, a
      reorganization of the cytoskeleton because of alpha-actin redistribution, and the
      disturbance of the spatial orientation of blastomeres. As a result, the
      development of two-celled mouse embryos stops, and they do not reach the stage of
      blastocyst. These data show the significant role of geomagnetic fields in the
      normal growth of embryonic cells in vitro and the regulation of mammalian
      embryogenesis.

PMID- 18819292
TI  - Rats, cats and scorpions: children's hallucinations in paediatric intensive care.

PMID- 18819293
TI  - Human rights and restraints.

PMID- 18819294
TI  - Tapentadol a 'realistic alternative' to strong opioids for severe pain.

PMID- 18819295
TI  - HIV testing in dementia: clinical, ethical and patient safety implications.
AB  - This article presents patient safety issues along with the professional and
      ethical challenges in relation to UK guidelines on HIV testing in patients who
      are incapacitated as a result of dementia. Current protocols are designed to
      protect the patient, but may have undesirable consequences for patients, carers
      and doctors.

PMID- 18819296
TI  - The ethical basis of making decisions about cardiopulmonary resuscitation.
AB  - This article outlines the clinical ethical concerns around decision making
      regarding cardiopulmonary resuscitation and how they resulted from lack of
      clarity in the formulation of the previous guidance. It then reviews new guidance
      and discusses its wider implications for doctors and patients.

PMID- 18819297
TI  - Endocrinology and the skin.
AB  - This article discusses various cutaneous features associated with endocrine
      disease, which are of general medical relevance. Many of these, such as features
      associated with hypothyroidism, are common, while others, such as features of
      adrenal insufficiency, are relatively rare but important.

PMID- 18819298
TI  - Leadership skills: a guide for the foundation year doctor.

PMID- 18819299
TI  - Intravenous urogram interpretation.

PMID- 18819300
TI  - Cardiovascular therapeutics.

PMID- 18819301
TI  - Ten steps to better communication.

PMID- 18819302
TI  - The blood film as a diagnostic tool.

PMID- 18819303
TI  - Hepatitis e: a UK perspective.
AB  - Hepatitis E is increasingly recognized as a cause of viral hepatitis within the
      UK and should be considered in any patient presenting with acute hepatitis.
      Mortality rates of around 4% have been described, but are even higher during
      pregnancy.

PMID- 18819304
TI  - Caval interruption: methods and indications.
AB  - Venous thromboembolism is a significant cause of morbidity and mortality
      worldwide. Anticoagulation is the preferred treatment, but is not feasible in
      some patients. Caval interruption is the treatment of choice for prevention of
      recurrent pulmonary embolism. This article looks at the development of caval
      interruption.

PMID- 18819305
TI  - Venepuncture technique training vs practice: a survey of foundation year 1
      doctors.
AB  - This survey investigated potential disparity between foundation year 1 doctors'
      formal undergraduate venepuncture training and their actual clinical practice. Is
      there still a high prevalence of needle and syringe use?

PMID- 18819306
TI  - Franz Torek (1861-1938): first successful resection of an oesophageal tumour.

PMID- 18819307
TI  - Potential complications of the blind technique of port insertion during
      laparoscopy.

PMID- 18819308
TI  - Neonatal white leg: a case of anatomical misjudgment.

PMID- 18819309
TI  - A case of the blues.

PMID- 18819310
TI  - Atrial pacing wires: an uncommon cause of postoperative hiccups.

PMID- 18819311
TI  - The cost of education: saving for school and university fees.

PMID- 18819312
TI  - Access to cancer drugs: local autonomy or local tyranny?

PMID- 18819313
TI  - Is there a role for thiopentone in modern anaesthetic practice?

PMID- 18819314
TI  - The Centers for Medicare and Medicaid Services (CMS) EHR demonstration project.

PMID- 18819315
TI  - Salivary hormonal levels in the menopause: to test or not to test.

PMID- 18819316
TI  - The 2007 annual report of the Regional Infant and Child Mortality Review
      Committee.
AB  - The mission of the Regional Infant and Child Mortality Review Committee (RICMRC)
      is to review infant and child deaths so that information can be transformed into
      action to protect young lives. The 2007 review area includes South Dakota's
      Minnehaha, Turner, Lincoln, Moody, Lake, McCook, Union, Hansen, Miner and
      Brookings counties. Although there were no deaths in 2007 that met the criteria
      of the Sudden Infant Death Syndrome (SIDS) in our region, there were three infant
      deaths associated with unsafe sleeping environments (including adult co-sleeping)
      that either caused or potentially may have caused these infants' deaths. We need
      to continue to promote the "Back to Sleep" campaign message of not only placing
      infants to sleep on their backs, but also making sure infants are put down to
      sleep on safe, firm sleeping surfaces and that they are appropriately dressed for
      the ambient temperature. Parents need to be aware of the potential hazards of co
      sleeping with their infants. Compared to nine such deaths in 2006, only four
      deaths in 2007 involved motor-vehicle crashes, none of which were alcohol
      related. Two drowning deaths illustrated the rapidity in which even momentary
      caregiver distractions can lead to deaths in children in and around water. Since
      1997 the Regional Infant and Child Mortality Review Committee (RICMRC) has sought
      to achieve its mission to "review infant and child deaths so that information can
      be transformed into action to protect young lives." For 2007, the committee
      reviewed 25 deaths from Minnehaha, Turner, Lincoln, Moody, Lake, McCook, Union,
      Hansen, Miner and Brookings counties that met the following criteria: Children
      under the age of 18 dying subsequent to hospital discharge following delivery.
      Children who either died in these counties from causes sustained in them, or
      residents who died elsewhere from causes sustained in the 10-county region. The
      report that follows reviews the committee's activities for 2007. No deaths
      meeting the criteria for Sudden Infant Death Syndrome (SIDS) occurred in the
      review region. The committee has observed a stable decline in the number of
      deaths due to the SIDS as compared to the eight SIDS or possible SIDS deaths
      occurring in 1999. Unfortunately, however, there were three infant deaths in SIDS
      like settings where asphyxia could not be excluded. Although the committee
      strives to be consistent year to year in its investigation protocols, we have
      noticed that the number of deaths classified as "undetermined" has been
      increasing over the last few years (starting in 1997: 1, 2, 1, 0, 2, 1, 2, 0, 5,
      4, 5). Although it is possible that deaths certified as SIDS in earlier years may
      now be classified as undetermined due to asphyxial risks, we may also be seeing
      an increase in infants sleeping in unsafe environments. Our data may be mirroring
      a national trend amongst death investigators to increasingly recognize asphyxial
      risks in infant death scenes. Infants co-sleeping with adults (two deaths in
      2007) may represent a risk factor not as frequently seen as in prior years. We
      will watch this trend closely in the future. The Committee strenuously advocates
      that the Back to Sleep message include placing infants on their back to sleep,
      avoiding soft bedding for infants, making parents aware of the potential hazards
      of co-sleeping with young infants, and eliminating both pre- and post-delivery
      fetal/infant cigarette smoke exposure. a decrease in youth motor-vehicle crash
      deaths to four versus the nine seen in 2006.2 Three of those dying in motor
      vehicle crashes in 2007 were not wearing seat belts. The committee continues to
      feel that some of these deaths could have been prevented had these children been
      wearing a seat belt. Compared to four alcohol-related motor-vehicle crash
      fatalities in 2006, no deaths in 2007 were alcohol related. The committee,
      however, is painfully aware that even one crash involving multiple occupants can
      rapidly skew the apparent improvements in 2007 in the wrong direction. In 2007,
      two youths, both with disabilities, drown. One drown in a bath tub and the other
      in an outdoor pool. It is unfortunate that these deaths bring home the message
      that even the smallest, momentary lapses in supervision of these children can
      have fatal consequences. Fortunately, the child and infant homicide rate in our
      region is very low. Unfortunately, however, one infant did die as a result of
      being assaulted and shaken by one of its parents. There remains a need for the
      community at large, and the medical community specifically, to address issues of
      parental anger management, particularly when caregiver frustration is directed at
      children.

PMID- 18819317
TI  - High dose acetaminophen in narcotic combinations: should there be concern?

PMID- 18819318
TI  - What is medication therapy management?

PMID- 18819320
TI  - Exploding manikins.

PMID- 18819319
TI  - Headache reflections: the role of classification, narrative and focused
      intervention.
AB  - Clearly the patient's history is paramount in determining whether a headache
      belongs in the migraine, chronic tension-type or other category. The multiple
      conditions in the other category can sometimes make definitive diagnosis a
      daunting challenge. Laboratory testing looking for hematologic or metabolic
      abnormalities may be advised, and brain imaging may be required. If an acute
      hemorrhage is anticipated, an unenhanced CAT scan may be sufficient. Relative to
      other pathologic possibilities, a MRI generally provides more specific and useful
      information. This is especially true when seeking to rule out a tumor or vascular
      abnormality (in which case a MRA, as well as a MRI, may be helpful). Most lay
      people recognize that headaches may, at least potentially, have a serious cause.
      Indeed, many patients with severe migraine and chronic tension-type headaches are
      greatly relieved to learn that some ominous pathology is not present. Of course,
      clinicians also worry about the causes of headache and are fearful of missing
      some potentially serious underlying pathology. Utilization of the conceptual
      framework of migraine, chronic tension-type or other headache does not guarantee
      an accurate diagnosis. But this approach can help, especially when the clinician
      appreciates the importance of an accurate patient history. Such focus can guide
      the determination of whether to initiate empiric treatment or to embark on a
      definitive diagnostic evaluation. Headaches are common, sometimes disabling and
      potential harbingers of dreaded pathology. Thoughtful assessment of every patient
      with headache is warranted.

PMID- 18819321
TI  - Physician consortium for performance improvement.

PMID- 18819322
TI  - SERV SD.

PMID- 18819323
TI  - [Difficulties in routine diagnostics of urothelium lesions].
AB  - BACKGROUND: Facing the increasing frequency of urothelial neoplasms and
      stratified therapeutic strategy pathologists have to meet the demands of
      urologists for constantly increasing preciseness of the histopathology reports
      influencing the application of tailored therapeutic schemes. The WHO/ISUP
      consensus conference in 1998 resulted into adoption of a new classification of
      the urothelial lesions. Its employment requires considering of features that can
      be difficult to find in the material provided. MATERIAL AND METHODS: parallel
      typing of more than 200 urothelial neoplasms from the daily routine biopsy
      samples provided by the faculty of medicine urology clinic according to the
      previous Mostofi 1973 and the new WHO/ISUP 1998 classification. RESULTS:
      Realizing the consultation demands we have identified some repetitive problems in
      the urothelium lesions diagnostics considering typing, grading, and staging of
      the lesions. Typing was a less frequent source of problems. It appeared in
      classifying lesions with inverted growth, and mucin producing urothelial
      neoplasms vs. adenocarcinomas. Less important typing problems are represented by
      uncommon rare diagnoses, as they manifest from the beginning as a specialty
      solvable mostly with the help of immunohistochemistry. Grading was experienced as
      troublesome in the following items: papillary hyperplasia vs. LG papillary ca,
      PUNLMP vs. LG papillary ca, HG papillary ca with a majority of LG material,
      monotonous types of HG flat lesions, and combined lesions. Staging difficulties
      applied mostly in identification of the initial unequivocal invasion and the
      substaging of pT1 into pT1a and pT1b with learning to find the decisive mucosa
      structures described in detail as late as 1983 (2). We have implemented reporting
      the presence/absence of the detrusor muscle in the material as a marker
      describing the representativness of the sample provided; we consider this
      approach less confusing than introduction of clinical staging terminology Ta, T1
      instead of pTa, pT1. To help the practising pathologists accustomed to the
      previous classification system we have organized postgraduate courses dealing
      with the application of the new diagnostic criteria adopted by the new version
      WHO 2004 urothelial neoplasms classification. A slide collection from the routine
      biopsy material comparing the previous and the new classification and a reference
      image database with commented reference images are being developed in the LUCIA
      Net image archiving system. Free access for study is available at
      http://www.laboratory-imaging.com. Recently, it includes over 80 images.
      CONCLUSION: adopting the new system of urothelial lesions classification requires
      consideration of formerly not employed features. The learning can be simplified
      with both classical slide collection & e-learning image database.

PMID- 18819324
TI  - [The 2007 World Health Organisation classification of tumours of the central
      nervous system, comparison with 2000 classification].
AB  - WHO Classification of Tumours of the Central Nervous System from the 2007 is
      distinguished from the previous 2000 classification by a few conceptual
      modifications, changes in the terminology and seven newly codified tumour
      entities. The text shows a short comparison of both classifications emphasising
      the most important changes from the surgical neuropathology point of view. The
      newly codified entities are: angiocentric glioma, pilomyxoid astrocytoma,
      papillary glioneuronal tumor, rosette-forming glioneuronal tumor of the 4th
      ventricle, papillary tumour of the pineal region, spindle cell oncocytoma and
      pituicytoma. Mostly, they are rare tumours already known from the literature.
      Based on new knowledge from the molecular pathology the paragraphs about tumour
      genetics were markedly changed. The complexity and diversity of tumours of the
      nervous system is enormous, and, not surprisingly, some problematic questions of
      classification and grading remain unresolved.

PMID- 18819325
TI  - Double immunostaining with CD1A and CD68 in the phenotypic characterization of
      indeterminate cell histiocytosis.
AB  - Indeterminate cell histiocytosis (ICH) is a rare disorder in which histiocytic
      cells proliferate, expressing markers of both X- and non-X histiocytosis.
      Nevertheless, it is not totally clear if both types of markers are co-expressed
      by the same cell in this disorder, or on the contrary, the histiocytosis is made
      of two phenotypically different types of cells. Some recent reports seem to
      indicate this latter option, since there is a non-homogeneous distribution of the
      cells in the dermis. The ones in the most superficial part of the biopsy would
      lose some of their markers when moving towards the bottom part of the dermis. In
      order to check if there is co-expression of CD1a and CD68 by the same cell, we
      performed an immunohistochemical study with double staining, in a case of ICH of
      a 74-year-old male, who presented multiple yellowish papules in chest, back and
      both arms. Their sizes varied between 1 and 3 mm. One of the biopsies from one
      lesion of the back showed a dermal histiocytic infiltrate, which expressed S-100,
      CD1a, Factor XIIIa and CD68 in the common immunohistochemical study. Birbeck
      granules were not found in the ultrastructural study. Our results with the double
      stain for CD1a and CD68 demonstrated that most of the histiocytes expressed
      either one marker or the other. Nevertheless, some of the histiocytes of the
      infiltrate co-expressed both markers. In all the cases, the cells with this
      combined phenotype were mononuclear. Although CD1a was mainly expressed by the
      cells at the top of the dermis, some cells of the deep dermis kept expressing
      this marker. The cells expressing both markers were mostly found in the top part
      of the dermis. The multinucleate cells expressed only CD68, but not CD1a.

PMID- 18819326
TI  - [Immunohistochemical detection of TTF-1 in intraoperative bioptic samples of
      adenocarcinoma of the lung: a year-long experience].
AB  - The thyroid transcription factor 1 (TTF-1) is a highly sensitive and specific
      marker of adenocarcinomas of pulmonary origin in differential diagnosis of
      solitary pulmonary nodules. Positivity of TTF-1 as a marker of primary pulmonary
      tumor could have a very high impact on surgical treatment strategy. From known
      protocols we developed the method of immunohistochemical investigation of
      intraoperative bioptic samples from frozen section lasting about 15 minutes.
      During last year, we applied this method on 30 cases of intraoperative bioptic
      samples. All investigated cases were verified by immunohistochemical examination
      from formalin-fixed and paraffin-embedded definite tissue samples. With the
      exception of two samples in which the result was inconclusive from both frozen
      and fixed tissue, all other samples revealed the same result. Our experience
      demonstrates that intraoperative immunohistochemical investigation of TTF-1 in
      proper consequences could be a very useful tool for routine practice.

PMID- 18819327
TI  - Tubulo-squamous polyp of the vagina.
AB  - We report a case of an 86-year-old female with a tubulo-squamous polyp of the
      vagina. Grossly, the polyp measured 2 x 1.5 x 1 cm. Histologically, it was
      composed of well-circumscribed nests of squamous cells with bland nuclei. Some of
      the squamous nests showed central spaces filled with necrotic debris. Small
      tubules were present at the periphery of some of the nests, and there were a few
      tubules unassociated with the squamous nests. Furthermore, several larger
      mucinous glands, some with apparent squamous metaplasia, were present. The stroma
      was fibrous and rather hypocellular. Surface of the polyp was covered by intact
      squamous epithelium, which was not connected with the underlying lesion. The
      recently described tubulo-squamous vaginal polyp represents a distinctive entity.
      To the best of our knowledge, only one study describing a series of ten cases has
      been reported in the literature to date.

PMID- 18819328
TI  - Confessions of a goutophile: Despite its treatability, gout remains a problem.

PMID- 18819329
TI  - Epidemiology of gout.
AB  - The incidence and prevalence of gout are rising, likely as a result of a changing
      pattern of risk factors. At-risk populations are growing, due to the fact that
      people are living longer. Longevity and current dietary and lifestyle choices
      have also contributed to increased rates of comorbidities associated with
      hyperuricemia and gout. The use of medications to treat such comorbidities also
      plays a role in some cases of gout. While dietary and lifestyle modification may
      be useful as adjunctive measures, such changes do not replace pharmacologic
      treatments for gout or associated comorbidities.

PMID- 18819330
TI  - The practical management of gout.
AB  - Gout management requires a comprehensive strategy that considers both acute and
      chronic aspects of the disease. Acute gout flares should be treated with anti
      inflammatory agents as rapidly as possible. The underlying hyperuricemia may be
      treated with urate-lowering agents initiated at a time appropriate for the
      individual patient. Successful urate lowering ultimately prevents flares and
      disease progression and should be started immediately in patients with advanced
      or tophaceous disease. When urate-lowering therapy is initiated, anti
      inflammatory prophylaxis should be used to reduce the risk of flares induced by
      abrupt changes in urate levels. Regular monitoring of serum urate can ensure
      therapeutic dosing of urate-lowering agents to achieve levels below 6 mg/dL,
      which are associated with a reduction in flares and tophi.

PMID- 18819331
TI  - [Simulation of the quality of life in patients with chronic obstructive pulmonary
      disease].
AB  - The statistically significant formulas calculated on the basis of statistical
      processing of the data of the Saint George test and physical, functional,
      laboratory, and radiation studies in 117 patients with chronic obstructive
      pulmonary disease (COPD) are given. Based on the external function test, the
      study has provided highly significant statistical formulas for calculating the
      subjective estimate of the severity of COPD, the degree of its associated
      psychological problems and overall distress due to COPD in the presence of moist
      rales and chronic cor pulmonale or in its absence.

PMID- 18819332
TI  - [Monitoring of tuberculosis recurrences: their causes and precipitating factors].
AB  - Introduction of unwarranted shorter courses of chemotherapy, physicians'
      decreased attention to pathogenetic treatments, nonadherence to the standard of
      examination while transferring to a further follow-up of clinically cured
      patients have increased a risk for early tuberculosis recurrences. In the years
      ahead, there may be a further rise in the number of late recurrences in the
      general population of the Russian Federation as preventive measures have
      deteriorated amongst the tuberculosis-cured individuals after their referral for
      the general health care system. The persons who have experienced tuberculosis and
      stricken off the register in a tuberculosis dispensary more than 5 years ago make
      up a late recurrence risk group.

PMID- 18819333
TI  - [Study of a risk for tuberculosis among medical students].

PMID- 18819334
TI  - [Multidrug pulmonary tuberculosis: sociomedical features and the efficiency of
      inpatient treatment].
AB  - Case histories of 147 patients with new-onset destructive pulmonary tuberculosis
      (PT) (infiltrative, disseminated, fibrocavernous) with the pathogen of the
      disease showing multidrug resistance (MDR) were analyzed, by evaluating the
      efficiency of treatment involving sputum abacillation after termination of the
      inpatient stage of treatment. A control group included 220 patients with PT of
      the similar lesion and clinical forms, who preserved drug resistance (DR) to
      antibacterial agents. Most patients with MDR disseminated destructive PT are
      young people aged 36.6 +/- 1.6 years, this disease-associated disabled
      individuals (65.3%), alcoholics (48.3%), opium addicts (11.5%), ex-prisoners
      (26.5%), single, homeless; more frequently suffer from gastrointestinal (40%) and
      chronic nonspecific lung (24.5%) diseases. The course of MDR PT is significantly
      more commonly complicated by the development of respiratory failure (48.9%) and
      hemoptysis (6.1%) (in DR PT 19.1 and 2.3%, respectively). In terms of negative
      smear tests and the results of sputum cultures, the abacillation rates were 70.1
      and 67.3%, respectively (in DR PT, these were 88.18 and 86.34%, p = 0.01). A
      negative reaction of sputum occurred in 42.1% of patients at 2-3 months of
      treatment while its culture did in 46.2% at 4-5 months. In the control group
      wherein drug sensitivity of M. tuberculosis was preserved, sputum abacillation
      occurred in the larger proportion of the patients within the first 2 months (in
      68.6 and 56.3% of cases with sputum smear and culture, respectively). The
      efficiency of inpatient therapy is greatly affected by short-term treatment
      caused by voluntary withdrawal and irregular uses of antituberculous drugs,
      mainly due to alcoholization.

PMID- 18819335
TI  - [The optimizing effects of combined use of antistress psychophysiological
      correction in the complex therapy of patients with new-onset pulmonary
      tuberculosis].

PMID- 18819336
TI  - [Plasma levels of cytokines in patients with active infiltrative pulmonary
      tuberculosis].
AB  - The levels of interferon-y (IFN-gamma), tumor necrosis factor-gamma (TNF-alpha),
      and interleukin-8 (IL-8) and their changes during chemotherapy and laser
      chemotherapy were studied in 97 patients with active infiltrative pulmonary
      tuberculosis, by taking into account Mycobacterium tuberculosis (MBT) sensitivity
      to chemical agents. The studies have indicated that the levels of IFN-gamma, TNF
      alpha, and IL-8 are increased and may be markers of an active process.
      Chemotherapy causes a reduction in increased cytokinemia. Complex laser
      chemotherapy affects the cytokine profile in active tuberculosis caused by not
      only drug-sensitive, but also drug-resistant MBT.

PMID- 18819337
TI  - [The experience of applying of exogenous monoxide of nitrogen and argon plasma
      coagulation by cavernotomy in patients with fibro-cavernous pulmonary
      tuberculosis with the presence of multiple drug resistance].
AB  - The presented paper discusses the experience with exogenous nitric oxide (NO) and
      argon plasma coagulation (APC) used at cavernotomy in 31 patients with multidrug
      resistant fibrocavernous pulmonary tuberculosis. Supplementary treatments
      depending in infectious risk factors were comprehensively evaluated. The
      application of APC and NO significantly improved the results of open cavern
      sanitation, as evidenced by the bacterial excretion index, and doubled the
      immediate efficiency of surgical treatment.

PMID- 18819338
TI  - [Postmortem diagnosis of the major forms of tuberculosis (according to autopsy
      data)].

PMID- 18819339
TI  - [Atherothrombosis: state-of-the-art review and approaches to the problem].
AB  - Acute ischemia resulting from arterial lesions poses a real threat to mankind.
      The concept of atherothrombosis aims to unite doctors of different specialities
      to combat this pathology; it suggests active exchange of experience in the
      management of aherothrombosis between representatives of different medical
      disciplines. The concept is expected to promote treatment of the patients. The
      common pathogenetic mechanism of ischemic disorders of the heart, brain, and
      lower extremities provides a basis for the recommendation of active
      antithrombotic therapy for their prevention. The current approach to the
      management of atherothrombosis is prone to further improvement despite certain
      reports of successful inpatient treatment of acute myocardial infarction.
      Prevention of blood clot formation, i.e. prophylaxis of atherosclerosis, remains
      a challenging problem. Statins may prove of great help in this respect. Studies
      of the effect of infectious factors on the integrity of the fibrous envelope of
      an atherosclerotic plaque are currently underway.

PMID- 18819340
TI  - [Contribution of rennin-angiotensin-aldosterone system genes and NO synthase gene
      to the development of arterial hypertension].
AB  - Arterial hypertension (AH) is one of the most widespread cardiovascular
      disorders, 39.2% of men and 41.1% of women having elevated arterial pressure
      (AP). Hence, the necessity to elucidate possible causes of this abnormality.
      Heredity is considered to be a major factor determining AP in humans, and
      researchers all over the world are engaged in the search for AP markers. This
      paper is focused on genes controlling the renin-angiotensin-aldosterone system,
      viz. genes of angiotensin II, type 1 angiotensin II receptors, angiotensin
      converting enzyme, and NO synthase. An overview of population studies with
      special reference to these genes indicates that molecular-genetic mechanisms of
      AH remain unclear. Joint efforts of researchers working in different centres are
      needed to address the problem.

PMID- 18819341
TI  - [Fullerenes in the treatment of respiratory disorders].
AB  - Diseases of respiratory organs constitute a serious socio-medical problem in this
      country due to high morbidity, mortality, and disability rates. The development
      of medical nanotechnlogies opens up new prospects for the improvement of
      treatment and prevention of these pathologies. Of special interest is application
      of C60fullerenes with a broad spectrum of therapeutic activities and synthesis of
      their hydrated forms for enteral and parenteral administration producing no acute
      or chronic toxic effects.

PMID- 18819342
TI  - [Chronic constipation: current view of the problem].
AB  - The authors propose the definition of chronic constipations (CC) and present data
      on their incidence and classification along with a concise review of physiology
      and motor-evacuation function of the colon and defecation act. Pathogenesis and
      clinical symptoms of different forms of functional and organic CC are discussed.
      Instrumental and laboratory methods for the examination of patients with CC are
      described including special techniques for the diagnosis of abnormalities in the
      anorectal region. Special attention is given to modern approaches to individual
      therapy including correction of life style and dietary habits as well as the
      choice of adequate drug therapy. The proposed classification of purgative drugs
      takes into account indications for their use, contraindications, and adverse
      effects. Selected methods of physiotherapeutic and surgical treatment of CC are
      described.

PMID- 18819343
TI  - [Assessment of heart rate circadian rhythms in paroxysmal atrial fibrillation].
AB  - Heart rate (HR) variations during night sleep and in the early predawn period in
      healthy subjects and patients with paroxisms of artrial fibrillation were used to
      assess HR circadian rhythms. Daily ECG monitoring was performed in 19 healthy
      subjects (mean age 36.0 +/- 7.05 years) and patients with paroxisms of atrial
      fibrillation (mean age 55.15 +/- 3.91 years). In healthy subjects, HR
      responsiveness during night sleep and in the early predawn hours was more
      prominent than in patients with paroxisms of atrial fibrillation. The number of
      HR spikes at night was 20.42 +/- 3.73 and 14.23 +/- 2.8 (p < 0.001) and one hour
      before waking 3.74 +/- 1.33 and 1.92 +/- 1.04 (p < 0.001) respectively;
      premorning activation coefficient was 0.19 +/- 0.007 and 0.13 +/- 0.007 (p <
      0.05). It is concluded that HR responsiveness during the night sleep and the
      early predawn period in healthy subjects is higher than in patients with
      paroxisms of articular fibrillation. The number of HR spikes at night and one
      hour before waking as well as premorning activation coefficient can be used to
      assess RH circadian rhythms.

PMID- 18819344
TI  - [The role of cytokines in restenosing coronary stents and the efficiency of its
      secondary prophylaxis with statins].
AB  - This study was designed to assess the diagnostic value of dynamic patterns of
      anti-inflammatory cytokines (IL-1b, IL-6, TNF-alpha) in patients with ischemic
      heart disease (IHD) and restenosis of coronary stents 14 months after their
      implantation for long-term prophylaxis of dyslipoproteinemia. A total of 40
      patients with IHD of advanced functional classes (FC) were examined. Blood
      cytokine levels were measured before, 1 day, and 12-18 months after coronary
      stenting. Two groups of 23 and 17 patients included cases with recurrent angina
      and without it respectively. The main parameters measured in the study were in
      stent restenosis rate, incidence of' acute myocardial infarction (AMI), mortality
      rate, frequency of hospitalization for unstable angina, and the levels of
      proinflammatory cytokines. Considerable activation of cytokines in patients with
      post-infarction cardiac dysfunction who rarely resorted to therapy with statins
      (16.7%) was associated with the high rate of recurrent coronary insufficiency
      related to in-stent occlusion (8.7%), progressive atherosclerosis (65.2%),
      impaired myocardial perfusion, and restenosis of coronary stents (26.1%).
      Patients lacking apparent expression of serum cytokines after revascularization
      while receiving efficacious secondary prophylaxis of dyslipidemia (13.8 and 17%
      decrease of triglycerides (TG) and low density lipoproteins (LDL) cholesterol
      respectively, p = 0.04) had left ventricular ejection fraction (LVEF) improved by
      12.5% (p = 0.03%), left ventricular end diastolic pressure (LVEDP) decreased by
      15.8% (p = 0.03), and frequency of ischemic perfusion defect (PD) reduced by
      45.3% (p = 0.01). Moreover, they showed low incidence of progressive coronary
      atherosclerosis (17.6%) in the absence of in-stent restenosis. It is concluded
      that the frequency of restenosis of coronary stents after endovascular myocardial
      revascularization depends on the preprocedural rise in IL-1b content (R = 0.62, p
      = 0.0023). It is concluded that long-term secondary prophylaxis of
      dyslipoproteinemia in patients with ischemic dysfunction at risk of coronary
      restenosis effectively (more than thrice) decreases the occurrence of coronary
      stent restenosis after endovascular revasularization.

PMID- 18819345
TI  - [Peculiarities of the development and clinical course of myocardial infarction
      depending on solar activity].
AB  - Analysis of 214,908 calls for ambulance demonstrated a significant (p = 0.95)
      rise in the frequency of acute myocardial infanction (AMI) in men in a year of
      low solar activity (LSA) and in women during a year with high solar activity
      (HSA). The increased incidence of sudden death, clinical death, cardiogenic
      shock, and pulmonary oedema was associated with HSA. The largest number of calls
      for AMI patients was recorded between 9.00 and 12.00, the lowest from 3.00 to
      6.00. The frequency of AMI in the daytime was higher than at night. This
      difference was also apparent in "astronomic" seasons and half years with low and
      high solar activity. The incidence of AMI was highest during "astronomic" autumn
      and lowered in winter time. It was elevated in December of the LSA year and in
      May of the HSA year, in Mondays of HSA and Thursdays of LSA years. The minimal
      number of AMI episodes was recorded in weekends. Short daylight period and low
      air temperature combined with changes of atmospheric pressure and relative
      humidity during the cold period of the LSA year associated with a significant
      rise in the incidence of AIM. The overall frequency of AMI significantly
      increased during magnetic storms compared with the preceding days or immediately
      after them at both HSA and LSA. Mean daily frequency of AMI significantly
      increased within 24 hours before a magnetic storm only in the HAS year.

PMID- 18819346
TI  - [Left ventricular diastolic function in subjects with arterial hypertension
      living in the Far North depending on the work schedule].
AB  - Left ventricular diastolic function (LVDF) was studied in subjects with arterial
      hypertension (AH) living in the Far North in relation to their working regime. A
      total of 95 patients with grade I-II AH were divided into two groups, one
      including 53 dayworkers the other comprising 42 patients working in shifts. The
      control group included 25 practically healthy subjects. All the patients were
      examined by Doppler echocardiography. Analysis of the results demonstrated that
      patients with AH working night shifts more frequently experienced LVDF
      disturbances than subjects of other groups. These disturbances included increased
      contribution of the left atrial systole to left ventricle filling. Patients with
      AH exhibited the well-apparent dependence of left ventricle diastolic filling on
      the degree of its hypertrophy. LVDF was related to the elevation of nocturnal
      arterial pressure due to a rise in systolic AP.

PMID- 18819347
TI  - [Tissue factor molecules and some other indices of coagulation hemostasis in
      patients with rheumatic heart disease].
AB  - This comparative study of interleukins, tissue factor activity, and certain
      parameters of coagulation hemostasis included patients with rheumatic heart
      disease. It revealed an increased production of proinflammatory cytokines
      including interleukin-1b (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha)
      in all groups of patients. The procoagulative activity was also enhanced and
      positively correlated with the IL-1 beta level. Tissue factor activity was
      directly proportional to the concentration of IL-1 beta and inversely
      proportional to that of interleukin-4 (IL-4).

PMID- 18819348
TI  - [Painful syndrome in patients with ulcer disease in relation to intragastric pH].
AB  - Painful abdominal syndrome and diurnal fluctuations of pH values were
      investigated in 125 patients with different clinical variants of duodenal ulcer
      disease (DUD) in the phase of exacerbation. Fifty patients had uncomplicated DUD;
      it was complicated in the remaining 75 patients. The clinical course of the
      uncomplicated disease was characterized by moderate to severe painful
      hyperacidity syndrome coincident with the period of exacerbation, marked daily
      variations of pH, and manifest duodenogastric reflux (DGR). These made the
      patients opportunely apply for medical aid while acidification and alkalinization
      processes in the stomach prevented the development of complications. The
      complicated disease was associated with short-term pain or its absence, monotonic
      diurnal variations of acid production and alkalinization, weak DGR. Taken
      together, these clinical features explain why such patients less frequently apply
      for medical aid and eventually develop destructive complications.

PMID- 18819349
TI  - [The role of different factors affecting the duodenum in chronic viral hepatitis
      B].
AB  - The aim of the present study was to determine the frequency and the character of
      duodenal lesions in patients with chronic viral hepatitis B (CVH-B), to elucidate
      the dependence of these parameters on the activity and duration of hepatitis,
      virulence, and portal blood flow. A total of 206 patients with CVH-B were
      examined. It was found that CVH-B was associated with the development of chronic
      duodenitis in 23.3% of the patients. Endoscopic studies revealed different degree
      of affection of duodenal mucosa. Superficial focal and moderately severe
      duodenitis occurred more frequently (in 33.3 and 37.5% of the patients) than
      manifest duodenitis (12.5%). Erosive duodenitis concomitant with Helicobacter
      pylori infection was diagnosed in 16.7% of the patients. The main factors
      contributing to the development of chronic duodenitis included viral infection,
      its intensity, duration of hepatitis, and disturbed portal circulation. Severity
      of duodenitis was closely related to the severity of CVH-B.

PMID- 18819350
TI  - [Psychosomatic events in patients with digestive system disorders].
AB  - A total of 167 patients (92 men and 75 women) at the age of 45-65 (mean 47.4 +/-
      4.2) years with different digestive system disorders were examined in this study.
      One group included 48 patients with chronic non-atrophic (largely antral)
      gastritis associated with helicobacterial infection, the second one comprised 46
      patients with intestinal irritation syndrome, the third consisted of 36 patients
      with gastro-oesophageal reflux disease at the stage of unstable remission in the
      absence of symptoms of oesophagitis, and the forth group included 38 patients
      with chronic recurring duodenal ulcer. The Spielberger State-Trait Anxiety
      Inventory (STAI-i) test and Toronto Alexithymia Scale (TAS) test were used for
      the assessment. Correlation was estimated using the Spearman coefficient and
      multiple regression analysis based on the Statistica 6.0 and GraphhPad Prism 4
      statistical programs. It was shown that the overall alexithymia rate averaged
      66.8%. Taken together with the high occurrence of the reactive anxiety response
      (74.1%), it suggests a high degree of personality psychosomatization among the
      examined patients with different digestive system disorders. Patients of groups 1
      and 2 are characterized by significant positive correlation between the
      occurrence of the alexithymic personality type and the reactive anxiety response
      (r = 0.592, r = 0.593, p > 0.0001). This correlation was weak and insignificant
      in patients of groups 3 and 4 (r = 0.245, r = 0.190, p > 0.05).

PMID- 18819351
TI  - [Potential of combined hypoglycemic, antihypertensive, and hypolipidemic therapy
      in patients with diabetes mellitus and diabetic foot syndrome].
AB  - The objective of this study was to assess the potential of combined therapy in
      patients with types 1 and 2 diabetes mellitus (DM) and diabetic foot syndrome
      (DFS). A total of 157 patients with DFS were observed over 3 months including 25
      with type 1 DM and 132 with type 2 DM. In addition, 563 subjects without DFS were
      included in the study. Changes of arterial pressure (AP), carbohydrate and lipid
      metabolism under effect of hypoglycemic, hypolipidemic, and antihypertensive
      therapy combined with the local treatment of DFS were evaluated. Improvement of
      the glycemia level in patients with type 1 DM and DFS was achieved by intensive
      insulin therapy (IIT). Patients with poorly compensated type 2 DM (HbAc1 > 7%)
      and DSF were given IIT corrected with regard for obesity and insulin resistance
      (IR). Combined treatment of insulin with meformin or glyclaside with metformin is
      indicated to patients having compensated type 2 DM and a small ulcerative defect
      (Wagner's stages I-II) in the absence of infection, obesity, and IR. In patients
      with types 1 and 2 DM, AH, and DFS, AP was lowered by two- and three-component
      antihypertensive therapy respectively. Statins improved the lipid spectrum in
      patients with types 1 and 2 DM and DFS. The combined therapy having beneficial
      effect on AP, carbohydrate and lipid metabolism together with the local treatment
      and immobilization of the affected limb resulted in epithelization of ulcerative
      foot defects without amputation in 96 and 80% of the patients with type 1 and 2
      DM respectively.

PMID- 18819352
TI  - [Causes of pain in the knee joint].
AB  - Pain in the knee joint is one of the commonest complaints for which people seek
      an advice of different medical specialists. The aim of this study was to
      elucidate the cause of pain in patients with the alleged diagnosis of
      "osteoarthrosis" and to develop the relevant diagnostic algorithm. The study
      included 214patients aged from 35 to 85 years with a pain level of at least 40 mm
      by the visual analog scale (VAS). Results of physical and X-ray examination
      provided indications for further studies that were performed by ultrasonographic
      (40.1%), arthroscopic (52.3%), and MRT(64.2%) techniques. One third of the
      patients were aged women with the body mass index > 40.1 and stage 3
      osteoarthrosis (OA) in whom pain was attributable to primary osteoarthrosis. The
      remaining patients had pain of other origin. Ultrasound studies revealed rupture
      of the internal lateral ligament in 3, "pes anserinus" tendinitis in 5, and
      synovitis in 53 patients. MRT demonstrated traumatic and degenerative meniscal
      tear in 102 and rupture of the anterior cruciate ligament in 7 patients. Grade 3
      4 chondomalacia of the femoral condyle was diagnosed in 24 patients. There was
      excellent (98.6%) agreement between MRT diagnosis and arthroscopic data on
      lesioned intra-articular structures, articular cartilage, and subchondral bone.
      Arthroscopy revealed traumatic and degenerative meniscal tear in 85% patients,
      injured anterior cruciate ligament in 8%, signs of synovitis in 52.6%,
      chondromalacia of the femoral condyle in 57.6%, and isolated pathology of
      patellofemoral articulation in 33% of the patients.

PMID- 18819353
TI  - [Lumbosacral pain syndrome in sportsmen and ballet-dancer (diagnostic
      algorithm)].
AB  - There is presented an experience of the examination of 517 cases including
      sportsmen and ballet dancers, 15-45 olds, suffering from low back pain syndrome.
      265 patients were diagnosed with osteochondrosis, 105 cases--with spondylolis, 92
      -with facet syndrome, and 55 cases--with pelvic ligaments ligamentopathia. Based
      upon the analysis of the results of examination diagnostic algorithm and
      differential diagnostics of these diseases were developed. The use of the
      proposed algorithm in patients with dissimilar variants of low back pain syndrome
      showed its informational content. It permits to make a right diagnosis and apply
      an adequate therapeutic approach.

PMID- 18819354
TI  - [Posttraumatic posterior knee instability].
AB  - At the department of the sport and ballet trauma new methods of arthroscopic
      management of posterior posttraumatic knee instability (posterior static
      stabilization of knee joint with using of single-banded and double-banded
      transplants) in dependence on the kind, degree and form of instability, were
      worked out and implemented into clinical practice. Such methods permit to attain
      a compensated or subcompensated form of knee joint stability. Ad hoc methods of
      management were used in 23 patients (20 males and 3 females). A total of 62
      patients (51 males and 11 females) got operative treatment at the department,
      that permitted us to estimate fairly different methods of operative treatment of
      posttraumatic posterior knee joint instability. An operational intervention was
      performed in average 6 month after trauma. We received data in patients which had
      been treated with use of new methods of operative treatment as follows: good
      results were drawn in 93.3% (22 patients), satisfactory results--in 6.7% of cases
      (1 patient).

PMID- 18819355
TI  - [The formation of self-care in patients suffered from tetraplegia by dint of
      maxillofacial muscles and a tongue with use of electronic mechanical vehicle].
AB  - Method for the restoration of self-service ability in patients with tetraplegia
      was proposed. The use of the elaborated computer controlled device in creases the
      efficacy of rehabilitation. A basic realization of technical facilities and
      software can be further developed. In particular, the plan is drawn to expand the
      software functional for the possibility of prompt input of the required word from
      the dictionary. Application of this technology has shown to give a possibility
      toa great number of handicapped people with limitations in using a computer and
      thus realizing their intellectual potential in education, work and leisure to
      restore their self-service ability. A significantsocial and economic effect from
      the introduction of this technology into practice is expected.

PMID- 18819356
TI  - [The application of modern module hip and knee endoprostheses "mati-cito" in
      patients with tumors and postresectional femur and shin bone defects].
AB  - In the paper data concerning the use of new module hip and knee endoprostheses
      "MATI-CITO" in the course of conservative surgery in patients with large defects
      of femur and proximal shin-bone, arising during removal of tumors or developing
      as a result of side effects of preceding management, are presented. In given
      category of patients the causes of high-risk of complications diminishing an
      efficiency of operations are discussed. It was shown that sophistication of
      fabrication technologies and practical application of new endoprostheses gives an
      opportunity to significantly improve the functional results of treatment and to
      decrease of number of complications. The development such new medical
      technologies, as X-ray endovascular surgery, intraoperational reinfusion of own
      blood allows to decrease operational lethality, improve the performance status of
      patients and accelerate their rehabilitation

PMID- 18819357
TI  - [New conceptions in complex management of spine trauma patients including
      reconstructive microsurgery and succeeding rehabilitation].
AB  - This work is been based upon the experience of performing 100 reconstructive
      microsurgical operations with transplantation of combined vascular-neural
      autografts, in 24 cases--with introduction cellular material into zone of
      transplantation. The complex approach aimed to creating optimal conditions for
      the functional regeneration of the spinal cord (SC), including neurosurgical
      methods restoring anatomical integrity of the organ and also multicomponent and
      staging rehabilitation of patients has been developed. On the base of complex
      approach during a postoperative period there has been put synchronous
      multifactorial action, consisting of functional multichannel electrical pacing of
      muscles simultaneously participating in tumble. The patient concentrates all his
      attention on the trial to tumble with paralized extremities by himself. At that
      the series and the site of application of these electrical impulses forms the
      algorithm of this tumble. Synchronism of produced afferent and efferent impulses
      creates new possibilities in activating of regenerating processes in the damaged
      area of the spinal cord. As a result of treatment within the bounds of the
      developed program the authors get clinically and electrophysiologically proved
      certain improvement that they can not only predict but guarantee patients of this
      group. Presented here results of the complex treatment of patients with trauma of
      the spinal cord within the framework of research international program
      confidently testify advantages of the new approach to solving of this problem.
      For the first time in history of medicine there is created close cooperation and
      regular continuity between molecular biology, neurosurgery and rehabilitation.
      This scientific alliance permits in proper time to keep a close watch, quickly
      correct and improve every stage of treatment. The effect of implement of
      innovations is been summarized at the each next stage of proposed complex
      treatment and eventually significantly elevates an ultimate result of medical
      rehabilitation of invalids with trauma of the spinal cord.

PMID- 18819358
TI  - [Operative treatment of severe spine deformities].
AB  - 87 patients with scoliosis, 32 cases with kyphosis of a various etiology were
      operated. Patients with severe scoliotic deformations (the total angle 75-140
      [Russian character: see text]) got 2 types of the treatment. The first group
      consisted of 18 patients who were operated in two-stage surgery during the same
      anesthesia. In the second group (69 patients) after anterior diskectomy within 10
      20 days preliminary correction of deformation with halo-pelvic traction was
      carried out followed by main stage of operation the final dorsal correction of
      deformation with Cotrel-Dubousset instruments. A significant (more than 40%)
      correction of deformation was achieved in both groups. However in the 2nd group
      the value of main angle exceeded 90 [Russian character: see text]. There were
      operated 32 patients with severe kyphotic deformities. Out of them 15 patients
      had severe posttraumatic vertebral kyphotic deformations (dislocation fractures
      of III-IV type according to Denis classification), 11 cases had--postlaminectomy
      kyphoses, 6 patients suffered from Scheuermann-Mau's disease. The patients with
      dislocation-fractures underwent laminectomy, reposition of dislocation, and
      transpedicular fixation of the vertebral column. In 14 patients dislocation was
      reduced completely, in the one case partially, but in all cases stable
      spondylosyndesis was achieved. In 8 patients dislocation-fractures were
      complicated by paraplegia or rough paraparesis), the 3 cases showed practically
      entire regress after operation, in the 5 cases no evident improvement in the
      neurologic status occurred. Patients with postlaminectomy kyphoses were treated
      with wedge vertebrotomy at the top of a curve, dorsal correction and fixation of
      the vertebral column with CDI system. In the 4 cases there was noted significant
      improvement in the neurologic status. Patients with Scheuermann-Mau's kyphosis
      were treated with anterior multilevel diskectomy, followed by halo-pelvic
      traction, and later dorsal correction of deformation with CDI system. Treatment
      resulted in significant correction of deformation was achieved and physiological
      or close to physiological sagittal profile of spine was restored.

PMID- 18819359
TI  - [New diagnostic technologies in peripheral nerve injuries].
AB  - Based on experience of examination of about 300 patients with n. medianus and n.
      ulnaris injuries there are generalized new methodic possibilities in anatomical
      and functional approaches to diagnostics in peripheral neural trunks injuries. It
      is worth to include into the complex of diagnostic measures not only ENMG, but a
      set of other effective methods of investigation also. The use of modern clinical
      anatomical technologies (ultrasonography) permits as to detect areas of damage of
      the nerves, the sizes of diastasis and the location of the ends of the nerve, the
      presence and sizes of neuroma, as to evaluate the state of surrounding tissues,
      to reveal associated pathology. The application new clinical functional
      technologies (laser Doppler flowmetry with computer wavelet analysis of blood
      flow oscillations, computer thermography) allows to estimate the condition of the
      fine autonomous and sensor neural fibers. It empowers as diagnostics of
      functional condition of the nerve after trauma, as early detection the signs of
      tissue reinnervation after reconstruction of nerves and choice of the adequate
      tactics of management of such patients.

PMID- 18819360
TI  - [Biomechanics of pelvic ring and its structural elements].
AB  - Calculations and diagrams of the force distribution in pelvic bones' zone are
      presented. In persons without injuries and skeletal abnormalities all forces
      functioning on the pelvic ring are shown to be in balance. Proposed method of
      calculations enables to detect the treatment tactics (either conservative or
      operative management) in patients with pelvic bone fractures as well as in
      congenital abnormalities.

PMID- 18819361
TI  - [Low-intensity laser irradiation of blood for the correction of disturbed lipid
      metabolism in airmen].

PMID- 18819362
TI  - [Radon therapy in medical rehabilitation of patients with seronegative
      spondyloarthritis. An open controlled study].
AB  - Radon therapy of seronegative spondylitis in 213 patients proved much more
      efficient than symptomatic drug therapy due to its beneficial effect on
      peripheral arthritis and enthesitis. It stimulated cellular immunity and improved
      the quality of life in patients with seronegative spondyloarthritis to a higher
      degree compared with medicamentous treatment.

PMID- 18819363
TI  - [Effect of chlorine-sodium hydrocarbonate mineral water on the gastric secretory
      function in subjects with various daily motor activity patterns].
AB  - Effect of Shadrinskaya ID mineral water on the gastric secretory function was
      evaluated in wrestlers and subjects unengaged in sports activities.
      Characteristics of the observed functional response of the digestive system
      provided a deeper insight into the mechanisms by which mineral water along with
      the controlled muscular load acts on the secretory performance of the stomach.
      Specific changes of the gastric secretory function at rest and in the
      veloergometer test were documented in subjects with different patterns of daily
      motor activity. The knowledge of mechanisms of muscular tension and optimal ways
      to use mineral water may help to prevent negative manifestations of emotional and
      physical stress in athletes.

PMID- 18819364
TI  - [Low-intensity laser irradiation in the combined treatment of depressive
      disoreders in patients with chronic salpingo-oophoritis].
AB  - This study was designed to evaluate the possibility to use low-intensity laser
      radiation in combined therapy of somatogenic depressions in patients having
      gynecological problems, such as inflammatory disease of uterine appendages. It
      was shown that the combined treatment including administration ofantidepressants
      significantly accelerated the development of beneficial changes and stabilized
      depressive manifestations. Inclusion of low-intensity laser irradiation in the
      combined therapy further improved its positive effect. Nevertheless, the complete
      recovery could not be achieved in the absence of specific antidepressant
      treatment despite the alleviation of depressive symptoms.

PMID- 18819365
TI  - [Structure-resonance therapy in children with aftereffects of perinatal hypoxic
      lesions in the central nervous system].

PMID- 18819366
TI  - [Effect of summer holidays in a countryside recreational centre on orthostatic
      stability of circulation in children].
AB  - Orthostatic stability of circulation in young and elder schoolchildren was
      evaluated during their stay in the summer recreational centre. It was shown that
      a combination of health-promoting factors including natural and climatic
      conditions, enhanced motor activity, day regimen, nutrition, etc. had beneficial
      effect on the functional status of the children. It was manifest as the optimized
      blood flow response to assuming an active orthostatic position and the
      improvement of peripheral circulation at rest.

PMID- 18819367
TI  - [Novel technologies for the correction of aftereffects of deficient nutrition in
      the dietician practice].
AB  - Deficient nutrition is a common pathological factor encountered in medical
      practice. We evaluated results of combined intake of Essentuki-Novaya mineral
      water and Nutridrink artificial food mixture (Nutritia, Holland). Spa and resort
      therapy based on the use of natural factors and well-balanced nutrition resulted
      in the marked alleviation of clinical symptoms in patients with gastrointestinal
      disorders. Simultaneously, the consequences of deficient nutrition in the
      preceding period were corrected and manifestations of the main pathological
      syndromes decreased. It is concluded that a short-term course of oral
      alimentation using food substrate mixtures had beneficial effect on the health
      state of patients by improving their nutritional status and quality of life.

PMID- 18819368
TI  - [Interference therapy in patients with irritable bowel syndrome].

PMID- 18819369
TI  - [Influence of interval hypoxic training and sylvinite speleotherapy on physical
      working capacity and quality of life in patients with chronic obstructive
      pulmonary disease].

PMID- 18819371
TI  - [Use of computer programs for the evaluation of the efficiency of health
      improving treatment in a rehabilitation centre].

PMID- 18819370
TI  - [Use of millimeter range microwaves in the prevention of postoperative
      immuodeficiency].

PMID- 18819372
TI  - [Efficacy of non-medicamentous treatment of Chernobyl accident liquidators].

PMID- 18819373
TI  - [Physiotherapy of neurologic symptoms of lumbar osteochondrosis taking into
      account spinal biorhythms and topography of non-specific reflex muscular
      syndromes].

PMID- 18819374
TI  - [Efficiency and safety of hirudotherapy in ischemic cerebrovascular disorders].

PMID- 18819375
TI  - [Some physiological aspects of the mechanism of action of traditional health
      improving methods (Cigun, Indian, and Tibetan Yoga)].

PMID- 18819376
TI  - [An algorithm for the development of new preventive and curative technologies for
      restorative medicine (speculations, experience, results)].

PMID- 18819377
TI  - [Science, diplomacy, charity, politics... What is in common?--Academician Serhii
      Komisarenko].
AB  - The paper is dedicated to the history of creation and development of a new trend
      of scientific investigations in Palladin Institute of Biochemistry of NAS of
      Ukraine and Ukraine as a whole, - molecular immunology - in the context of
      scientific, scientific-organizational, pedagogical, social and political activity
      of Serhiy Vasyliovych Komisarenko. Professor S. V. Komisarenko, Director of
      Palladin Institute of Biochemistry, Full Member of the National Academy of
      Sciences of Ukraine and Academy of Medical Sciences of Ukraine, President of the
      Ukrainian Biochemical Society (since 1999), editor-in-chief Ukrainian Biochemical
      Journal (1989-1992 and since 1998), Academician-Secretary and Member of the
      Presidium of the National Academy of Sciences of Ukraine (since April 2004) is a
      physician by education, molecular biologist by the calling, biochemist
      immunologist by profession. He was one of the first researchers in our country
      who started systematic investigations in the field of molecular immunology,
      created a powerful world-famous scientific school, and made great contribution to
      solution of the acute problems of public health. He has proposed a new anti-tumor
      preparation MEBIFON which is produced at pharmaceutical firm Farmak in Kyiv. He
      was one of the first in the former USSR who introduced a hybridom technique for
      obtaining monoclonal antibodies. S. Komisarenko was awarded the State Prize of
      the Ukr. SSR (1979) for immunochemical investigation of milk for babies. He
      proved that small doses of total radiation cause essential inhibition of natural
      immunity, which he called "the Chernobyl AIDS". The collective of scientific
      workers of the Department of Molecular Immunology headed by S. Komisarenko was
      awarded the O. V. Palladin Prize of NAS of Ukraine (2003) for a cycle of works
      Immunochemical Analysis of Fibrin and Fibrinogen Polymerization Mechanisms.
      Serhiy Komisarenko combines successfully scientific, scientific-organizing
      activity with pedagogical work; he leads the division BIOTECHNOLOGY of the
      Department of Biochemistry at Taras Shevchenko Kyiv National University. Under
      his supervision 6 doctors and 18 candidates of science have been prepared. He has
      above 400 scientific articles in the field of Biochemistry and/or Immunology, and
      more than 100 publications on Ukrainian culture and politics. Serhiy Komisarenko
      has performed great social and political work at the post of the Deputy Chairman
      of the Council of Ministers of Ukraine, Deputy Prime Minister of Ukraine
      responsible for humanitarian sector (1990-1992), Ambassador of independent
      Ukraine in the United Kingdom of Great Britain and North Ireland (1992-1998). He
      is a trustee of activity of charitable organization of disabled children Special
      Olympics - Ukraine (since 2002). He was awarded a Diploma of the Supreme Council
      of Ukraine (2003), State Order of Merit (III degree - 1996, II degree - 1998),
      State Order of Prince Yaroslav the Wise (V degree - 2005). Serhiy Komisarenko was
      elected the Honorary Doctor of Kingston and North London Universities (1997). He
      has the Rank of Ambassador Extraordinary and Plenipotentiary of Ukraine.

PMID- 18819378
TI  - [Reversibility of energy-dependent Ca2+ accumulation in mitochondria].
AB  - Ca2+ accumulation in energized rat liver mitochondria has been studied after the
      blockage of mitochondrial permeability transition pore (MPTP) by cyclosporin A.
      It is shown that Ca2+ transport is coupled to the countertransport of protons:
      from the matrix of mitochondria in the medium in the course of Ca2+ accumulation,
      and, on the contrary, from the medium to mitochondrial matrix after membrane
      depolarization. In standard incubation medium containing K+, Cl-, oxidation
      substrate (glutamate) and inorganic phosphate (H2PO4(-)) the observed
      stoichiometry of the exchange is 1Ca2+ : 1H+. In accordance with this exchange
      ratio, proton, as well as cation, transport follows the same first-order
      kinetics, which is characterized in both cases by very close values of reaction
      half-times and rate constants. It is shown that reversion of Ca2+ -uniporter,
      sensitive to ruthenium red, is necessary for Ca2+ - efflux from the matrix
      ofdeenergized mitochondria when MPTP is blocked by cyclosporin A. It is also
      shown that Ca2+ -uniporter reversion takes place only after membrane
      depolarization and permeabilization by protonophore CCCP. Calcium release from
      mitochondria in the presence of CCCP is accompanied by proton flow into the
      matrix. Both calcium and proton fluxes are sensitive to Ca2+ uniporter blocker,
      ruthenium red, which gives the evidence of the identity of Ca2+ -efflux and
      influx pathways. The data obtained lead to the conclusion that calcium-proton
      exchange is necessary for Ca2+ -uniporter reversion and the reversibility of
      energy-dependent Ca2+ -uptake in mitochondria.

PMID- 18819379
TI  - [Calixarene-dependent hydrolysis of ATP. I. Kinetics and complexation of the
      calixarene C-107 with nucleoside triphosphate].
AB  - It was shown that calix[4]arene bis-aminomethylphosphonic acid C-107 can
      hydrolyze ATP. The kinetic curve of the ATP hydrolysis induced by calixarene C
      107 was nonhyperbolic and had a tendency to plateau (in the course of time)
      observing from 45-60 minutes of the incubation period when the reaction
      practically came to the end. The empirical kinetic characteristics of this
      reaction were calculated. The velocity of calixarene-dependent hydrolysis of ATP
      exceeds the velocity of spontaneous hydrolysis of ATP at least 14-15 times. The
      "Host-Guest" complexation of the calixarene C-107 with adenosinetriphosphate in
      acetonitrile/water (47/53 v/v) solution was investigated by the reversed-phase
      high performance liquid chromatography. The dissociation constants of the 1:1
      "Host-Guest" complexes ofATP-Guest with the calixarene-Host when using two
      columns Zorbax CN and LiChrosorb RP 18 within 197-231 microM were determined from
      the capacity factor of the Guest and concentration of the calixarene-Host in the
      mobile phase. The electrostatic, ion-dipole, dipole-dipole C-H-pi and other weak
      interactions in the "Host-Guest" complexes were discussed. Obtained data can be a
      basis for designing the synthetical ATP-hydrolyzing catalysts and also for
      subsequent investigation of both enzymatic and nonenzymatic ATP hydrolysis
      reaction,processes of ATP-dependent Ca2+ -transporting in subcellular membrane
      structures.

PMID- 18819380
TI  - [Effect of 2,4-dinitrophenol on the rat liver respiratory activity and ATP
      content after hypothermic storage and following reperfusion].
AB  - The influence of oxidative phosphorylation uncoupler 2,4-dinitrophenol (DNP)
      presence in preserving solution on the rat liver respiratory activity and ATP
      content after 18 h of hypothermic storage (HS) and following normothermic
      reperfusion (NR) was investigated. DNP presence on the HS stage led to decrease
      of ATP level as compared with the control. After DNP removal during NR the
      gradual recovery of oxidative phosphorylation coupling occurred. This fact
      resulted in improvement of mitochondrial functional state (V4 respiration rate
      decrease, respiratory control and ATP level increase).

PMID- 18819381
TI  - [S-nitrosoglutathione induced nitrosative stress in yeast: modifying role of
      catalases].
AB  - Possible role of catalases in modification of yeast Saccharomyces cerevisiae
      response to nitrosative stress was studied in the work. Yeast cell of a wild
      strain and catalase-defective strains were treated with nitric oxide donor S
      nitrosoglutathione, then the cell survival rate, and the levels of protein
      carbonyls and oxidized glutathione were measured. It was shown that S
      nitrosoglutathione decreased cells viability of wild and catalase-defective
      strains. Unexpected, yeast cells defective by both catalases survived
      successfully as compared with the cells of the wild strain. The intensity of
      stress was evaluated by measures of oxidative protein modifications and
      glutathione oxidation. Treatment with S-nitrosoglutathione did not affect the
      level of protein carbonyls and was lower by about 14 i 22 % in the cells of
      double mutant strains after treatments with S-nitrosoglutathione in
      concentrations of 10 and 20 mM. S-nitrosoglutathione induced a strong increase of
      the level of oxidized glutathione in yeast cells of the wild strain. This stress
      slightly increased the level of oxidized glutathione in the yeast cells defective
      by peroxisomal or both catalases. It is interesting, that an increase of oxidized
      glutathione level was not observed in the yeast cells defective by cytosolic
      catalase. The obtained results prove that catalases can modify yeast cell
      response to the nitrosative stress.

PMID- 18819382
TI  - [Change in glutathione content in rat thymocytes under apoptosis induced by H2O2
      or irradiation].
AB  - Glutathione (GSH) content as well as GSH-peroxidase and GSH-reductase activity in
      isolated rat thymocytes X-irradiated in a dose of 4.5 Gy or treated with 0.1 mM
      H2O2 were studied in a period preceding the appearance of apoptosis morphological
      symptoms. The early adaptive response of thymocytes to radiation - increase of
      both GSH content and glutathione peroxidase and glutathione reductase activity
      was revealed. On the contrary the rapid fall of GSH level in H2O2-treated
      thymocytes was observed simultaneousely with glutathione reductase inhibition and
      enhanced GSH consumption by glutathione peroxidase, this disbalance of GSH
      dependent antioxidant system probably facilitates mitochondrial way of apoptosis.

PMID- 18819383
TI  - [Influence of cattle cord blood fraction below 5 kD on biochemical parameters of
      blood in experimental chronic stomach ulcer in rats].
AB  - Influence of cattle cord blood fraction (below 5 kD) on lipid peroxidation
      product content and alkaline phosphatase activity-in peripheral blood was studied
      on the experimental subchronic stomach ulcer model in rats. It has been shown
      that the fraction administrations normalize thiobarbituric-active product content
      and alkaline phosphatase activity in blood, which testifies to decreasing
      inflammatory reaction in the mucous membrane of the stomach. The fraction
      administrations accelerate the processes of regeneration of the mucous membrane
      of the stomach up to complete healing of ulcer defects. Cord blood fraction below
      5 kD from cattle possesses antiulcer activity which is analogous to the actovegin
      activity. It has been shown by gel-penetrating chromatography that the pattern of
      cord blood fraction low molecular substances is different from the actovegin
      pattern both qualitatively and quantitatively.

PMID- 18819384
TI  - [Heme oxygenase activity in the tissues of the vessels and heart of rats under co
      administration of NO-synthase inhibitor and hemin chloride].
AB  - The administration of hemin chloride in a dose of 1.5 mg/100 g of the body weight
      was found to cause accumulation of the total heme and TBA-reactive products in
      the rat blood serum and vessels. Pretreatment by N(omega)-nitro-L-arginine (0.5 h
      before hemin chloride administration) did not affect the dynamics of the total
      heme and TBA-reacting products accumulation. The increase of heme oxygenase
      activity was observed in the vessels after hemin chloride administration. This
      effect was strengthened by N(omega)-nitro-L-arginine pretreatment. The changes of
      heme oxygenase activity and the total heme level in heart were not observed at
      any periods studied. The increase of the TBA-reactive products level in the heart
      after exogenous hemin injection was accompanied by an increase of nitrites
      content and blocked by pretreatment of NOS inhibitor. The N(omega)-nitro-L
      arginine alone caused the accumulation of the total heme, TBA-reacting products
      and the increase of heme oxygenase activity in the vessels. The role of heme and
      NO in regulation of the heme oxygenase activity is discussed.

PMID- 18819385
TI  - [Disorders in lipid composition and properties of plasma membrane in epithelial
      cells of the placental villous chorion in chlamydial infection].
AB  - Lipid composition of plasma membranes of placental epithelial cells of villous
      chorion of healthy women and those with chlamydiosis has been studied. Lipid
      composition of plasma membranes of ill women differs from that of healthy women
      by reduction of total phospholipids quantity, by the increase of the level of
      free cholesterol and free fatty acids. A disturbance in the ratio between certain
      lipid fractions and increasing quantity of lysophospholipids is observed. Two
      fold oppression of plasma membranes Na+, K+ -ATPase activity of placental
      epithelial cells of villous chorion in ill women has been detected but Mg2+, Ca2+
      -ATPase activity has not changed. Thus chlamydial infection causes significant
      disorders in lipid composition and functioning of epithelial cells membranes of
      chorion.

PMID- 18819386
TI  - [Phospholipase D activity in maize seedling roots under salt stress and presowing
      treatment by preparations of adaptogenic action].
AB  - The effect of different salinity level and synthetic compounds treatment on
      phospholipase D activity in the root tissue of maize seedlings and the content of
      phosphatidic acid in plasmatic membrane has been investigated. The salt
      exposition to 0.05 M NaCl raised the activity of phospholipase D and the content
      of phosphatidic acid in the plasma membrane. The salt exposition to 0.1 M NaCl
      lowered the activity of phospholipase D, but raised the content of phosphatidic
      acid in the plasma membrane. The synthetic compounds treatment increased the
      activity of phospholipase D. It was shown that methyure treatment decreased the
      content of phosphatidic acid in the plasma membrane. The ivin treatment had the
      opposite effect.

PMID- 18819387
TI  - [Effects of anesthetics on oxidative stress changes in patients with high
      anesthetic risk in the perioperative period of coronary bypass surgery].
AB  - The study included 44 patients who were divided into 3 groups according to the
      type of anesthesia. In group 1 patients (n = 15), initial anesthesia was
      accomplished by inhaled sevoflurane and intravenous fentanyl (2.5-3.5 microg/kg);
      basal anesthesia was performed with sevoflurane. In Group 2, midazolam, 0.1-0.15
      mg/kg, fentanyl, 5.2 +/- 0.01 vg/kg, and ketamine, 0.85 +/- 0.13 mg/kg were given
      for induction. Basic anesthesia was carried out, by administering fentanyl in a
      dose of 4.71 +/- 0.4 microg/kg/hour, halothane, 0.5-1.5 ob %. In Group 3,
      midazolam, 1.2 +/- 0.01 mg/kg) and fentanyl, 7.8 +/- 0.6 microg/kg) were used to
      induce anesthesia. Basic anesthesia was effected with fentanyl, 5.31 +/- 0.5
      microg/kg/hour, ketamine, and diprivan. Anesthetic management using halogen
      containing inhalational anesthetics at coronary bypass surgery in patients at
      high anesthetic risk was ascertained to cause a significant reduction in the
      degree of manifestations of oxidative stress and facilitated a better
      intraoperative period. Sevorane was found to have the most significant effect on
      oxidative stress.

PMID- 18819388
TI  - [Prevention of regurgitation and aspiration during emergency care of patients
      under general anesthesia].
AB  - This study has provided new data on methods for preventing regurgitation and
      aspiration under general anesthesia, by using parenteral and enteral antacids as
      premedication in urgent surgery. There is evidence that with 60-minute delay in
      starting surgery, omeprazole, 40 mg, has the highest alkalizing effect. Second-
      and third-generation H2-blockers have a persistent and good antacid effect. In
      emergencies, 30 ml of 3% sodium citrate solution show a rapid and effective
      antacid effect, which eliminates or drastically reduces the likelihood of
      aspiration pulmonitis even in case of regurgitation and aspiration of the gastric
      contents. Based on the findings, the authors have developed a patient preparation
      protocol for general anesthesia in urgent surgery as the standard for the
      practical use in general anesthesiology.

PMID- 18819389
TI  - [Tracheoesophageal fistulas in anesthetic and intensive care practice].
AB  - The paper analyzes the etiology and pathogenesis of respiratory organ fistulas
      and their prevention and various treatment options (radical and palliative
      surgery and medical therapy). Particular attention is given to tracheoesophageal
      fistulas that are iatrogenic complications in anesthetic and intensive cares. The
      experience in treating the patients at the Department of Thoracic Surgery,
      Russian Research Center of Surgery, Russian Academy of Medical Sciences, before
      1991 and from 1992 to 2007 is analyzed. Today's approach to the etiology and
      therapy for this severe iatrogenic complication is determined by the development
      of measures to prevent this complication and by the change in treatment policy in
      favor of early radical surgical interventions.

PMID- 18819390
TI  - [Etiology of postoperative bacteremias in an intensive care unit: an association
      with the level of procalcitonin].
AB  - The etiology of bacteremia determines the choice of adequate therapy for severe
      infections. The clinical manifestations of gram-negative and gram-positive
      bacterial infections are similar while biological markers may serve as a guide
      for the early diagnosis of the nature of a pathogen. The paper analyzes data on
      the rate and etiology of bacteremia in 1360 patients at the A. N. Bakulev
      Research Center of Cardiovascular Surgery over a period of 5 years (2002-2006).
      The purpose of the study was to assess an association between the level of
      procalcitonin (PCT) and the etiology of bacteremia. A hundred and fifty
      consecutive cases of documented bacteremia were analyzed in detailed in 113
      cardiac surgical patients in the postoperative period, by comparing them with the
      level of on concurrent blood sampling for culture and PCT. In the gram-negative
      bacteremia group, plasma PCT levels were statistically significantly higher than
      in the gram-positive bacteremia group (5.40 and 0.86 ng/mg, respectively; p =
      0.000000). On constructing a characteristic curve, the authors determined the PCT
      cut-off value of 5.2 ng/ml for the differential diagnosis of gram-negative and
      gram-positive bacteremia with the maximum (86%) specificity and more than 50%
      specificity. Thus, when patients with suspected infections have plasma PCT
      levels, the leading value of gram-negative microorganisms may be supposed just
      before obtaining blood culture results.

PMID- 18819391
TI  - [Effect of mexidol on the magnitude of a systemic inflammatory response in
      patients at aortocoronary bypass surgery].
AB  - OBJECTIVE: to evaluate the efficiency of pharmacological correction of a systemic
      inflammatory response in patients after coronary bypass surgery, by using
      mexidol. SUBJECTS AND METHODS: 40 patients with coronary heart disease, who had
      undergone myocardial revascularization were examined. A study group (n = 20)
      received mexidol within 5 days before, during, and 5 days after surgery. A
      control group (n = 20) were given 0.9% NaCl solution. The degree of a systemic
      inflammatory response was estimated from the levels of C-reactive protein (CRP),
      the cytokines IL-6, IL-8, and TNF-alpha. The activities of serum enzymes and
      myoglobin were determined. RESULTS: after surgery, both groups showed the
      elevated concentrations of IL-6, IL-8, TNF-alpha, and CRP, but their elevation
      was statistically significant less in the study group than in the control one (p
      < 0.05). In both groups, there were increases in the levels of alanine
      aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase,
      lactate dehydrogenase, creatinine phosphokinase, and myoglobin, which was
      statistically significant more apparent in the control group (p < 0.05).
      CONCLUSIONS: mexidol diminishes the magnitude of a systemic response after
      aortocoronary bypass surgery under extracorporeal circulation and has an organ
      protective effect.

PMID- 18819392
TI  - [Sipping as a mode of correction of protein-calorie deficiency in intensive care
      unit patients].
AB  - The paper presents the results of postoperative studies in 82 patients with major
      soft tissue phlegmons of the extremities and torso. The basic aspect of the
      studies concerned the correction of protein-calorie deficiency on the basis of
      additional nutrition through sipping of hypercaloric formula "Nutridrink" and the
      standard enteral formula "Nutrisone dry powder", which were given to in 29 and 20
      patients, respectively, on postoperative day 1 for 3 weeks. A control group
      comprised 33 patients who received only diet 1. The findings have indicated that
      sipping of the enteral formula substantially reduces the catabolic pattern in the
      patients and facilitates a rapider recovery of the visceral protein pool.

PMID- 18819393
TI  - [Impact of hyperbaric oxygen therapy on the clinical course of acute pancreatitis
      and systemic inflammation response syndrome].
AB  - Feasibility of hyperbaric oxygen therapy (HBO) as an efficient and safe adjunct
      to the standardized treatment protocol and its possible immunomodulatory impact
      were assessed in the prospective and controlled study of 44 patients with
      diagnosed acute pancreatitis (AP). The course of the disease was accompanied by
      systemic inflammatory response syndrome (AIRS) in all the patients on admission.
      The impact of AP and HBO on homeostasis, the number of performed operations,
      mortality rates, the levels of two cytokines, intraabdominal pressure, and side
      effects caused by HBO were evaluated. A treatment group consisted of 22 patients
      receiving HBO therapy for 3 days (twice a day) using a monoplace chamber under
      pressures of 1.7-1.9 ATA. Patients (n = 22) in the control group were managed in
      accordance with the standardized treatment protocol. The authors found more
      stable homeostasis, decreased mortality rate, and the number of operations in the
      HBO group. This type of additional therapy, possibly contributed to the decrease
      of intraabdominal pressure within the first six days after admission. The
      findings suggest HBO can affect an inflammatory response, by decreasing the
      levels pro-inflammatory cytokines and increasing those of anti-inflammatory ones.

PMID- 18819394
TI  - [Hepatic protection in patients with generalized purulent peritonitis complicated
      by sepsis].

PMID- 18819395
TI  - [Early fibrobronchoscopy and the microbial flora composition of bronchoalveolar
      lavage fluid in patients with concomitant injury during treatment in intensive
      care units].
AB  - Resuscitative bronchofibroscopy in victims with severe injury and aspiration has
      been shown to be both a method for diagnosing damages to the bronchus and lung
      and that for recovering airway patency in them. The most common involvement (47%
      of cases) in chest injury has been noted to be the lower lung with the
      development of pyoinflammatory processes caused by etiologically significant
      microorganisms, such as Staphylococcus aureus and types of Enterobacteriacea, in
      most cases (more than 50%).

PMID- 18819396
TI  - [Intra- and postoperative correction of bradycardia by transesophageal electric
      stimulation].
AB  - The authors describe a case of clinical use of transesophageal pacing to correct
      drug-induced bradycardia during anesthesia, surgery, and in the early
      postoperative period in a geriatric patient with severe cardiovascular
      comorbidity who has been long receiving a beta-adrenoblocker. They show it
      possible to employ the procedure long in the therapy of bradyarrhythmias
      resistant to the cholinolytic atropine.

PMID- 18819397
TI  - [Malignant hyperthermia: pharmacogenetically caused acute massive
      rhabdomyolysis].

PMID- 18819398
TI  - [Intravenous paracetamol used for postoperative analgesia].

PMID- 18819399
TI  - [The physiological effects of adrenaline and the clinical application of
      epinephrine].

PMID- 18819400
TI  - [Rotaviruses in younger children in Novosibirsk in 2005-2007: detection and
      genotyping].
AB  - Examination of 1898 patients with acute enteric infection from March 2005 to
      February 2007 showed that group A rotaviruses were the most frequent cause (35%)
      of acute gastroenteritis among children under 3 years of age. Majority of cases
      of rotavirus infection was detected in infants under 1 year of age (71.8%). The
      peak of sporadic incidence was observed between February and May. High rate of
      mixed infection (45.6%) was observed - associations of rotaviruses with other
      viruses (noroviruses, astroviruses) and bacteria (Salmonella, Shigella,
      enteroinvasive Escherichia coli, Campylobacter, and opportunistic species) were
      detected. P- and G-genotypes of 337(50.8%) isolates of group A rotaviruses were
      determined by RT-PCR. The most prevalent strain was P[8]G1 (54.6%) followed by
      P[8]G3 (10.7%), P[8]G9 (8.6%), P[4]G2 (8.3%), and P[8]G4 (4.5%) genotypes.

PMID- 18819401
TI  - [Interaction of S- and R-lipopolysaccharides of Francisella tularensis with
      lypopolysaccharide-binding protein of human serum].
AB  - Investigation of ability of Francisella tularensis S- and R-lypopolysaccharide
      (LPS) preparations as well as the live bacteria with different chemotypes to
      interact with human lypopolysaccharide-binding protein (LBP) was carried out. It
      was found that LPS preparations derived from virulent(S-LPS) or isogenic
      avirulent mutant (R-LPS) strains of F. tularensis had markedly lower affinity to
      LBP as compared with typical S-LPS of Salmonella abortus and R-LPS of Yersinia
      pestis. It was shown that R-LPS preparation from avirulent mutant binds LPB more
      effectively than S-LPS from F. tularensis virulent strain. Differences in S- and
      R-LPS affinity were also confirmed for LPS represented by the live cells. Thus,
      bacteria with S-chemotype of LPS (F. tularensis 15/10) bound only 20.3% of LBP,
      whereas cells with R-LPS (F. tularensis 543 cap(-)) bound 39.9%. Such pattern was
      observed in experiments with both normal non-immune human serum and sera from
      people immunized with live tularemia vaccine. The latter indicates that
      opsonization of LPS by specific antibodies does not change its affinity to LBP.
      The observed more efficient binding of avirulent strain R-LPS to LBP is likely
      determines the more intensive host response directed to destruction and rapid
      elimination of the causative agent. At the same time, weak affinity of the
      vaccine and virulent strains S-LPS to LBP probably allows the bacterium to avoid
      activation of host defense mechanisms thus contributing to its long-term
      persistence in microorganism and development of specific immunity against
      tularemia.

PMID- 18819402
TI  - [Antagonistic activity of bacteria from Bacillus genus against dermatophyte
      fungi].
AB  - Antagonistic properties of the strain Bacillus subtilis IB-54 with respect to
      dermatophyte fungi Trichophyton rubrum, T. mentagrophytes var. gypseum,
      Microsporum canis was studied. The studied strains of bacilli effectively
      inhibited growth and development of dermatophytes when were cultivated on the
      media containing different carbon sources. Experiments on laboratory animals
      showed that B. subtilis IB-54 displayed no virulence, toxicity, and toxigenicity
      and can be considered as perspective object for development of antimycotic drugs.

PMID- 18819403
TI  - [Prevalence of type III secretion system genes in cholera vibrios from different
      serogroups].
AB  - Prevalence of vcs genes coding the type III secretion system (T3SS) in cholera
      vibrios of different serogroups isolated in Russia and neighboring countries was
      studied for the first time. Virulent strains of O1 and O139 serogroups as well as
      toxigenic Vibrio cholerae strains of other serogroups contained no T3SS genes.
      Unlike mentioned strains, 29.2% of atoxigenic non O1/non O139 cholera vibrios
      isolated from patients in Russia and neighboring countries contained the T3SS
      genes cluster, which might contribute to the pathogenic properties of these
      strains.

PMID- 18819404
TI  - [Virulence of pre-CTXphi-carrying Vibrio cholerae: genotypic and phenotypic
      characteristics].
AB  - AIM: Complex assessment of virulence of cholera vibrios carrying the truncated
      CTX element (pre-CTXphi prophage). MATERIALS AND METHODS: Twenty-two strainsof
      Vibriocholerae O1 and non-O1/non-O139 were studied by PCR and laboratory models.
      RESULTS: Genomes of all strains, besides pre-CTXphi genes, contained genes hapA
      (hemagglutinin/proteases), cef (CHO cell elongating factor), rtxA (high-molecular
      cytotoxin), and rtxC (its activator). Nucleotide sequences of rtxA and vgrG genes
      from ACD domains, genes VPI and VPI-2 from islands of pathogenicity, mshA
      (mannose-sensitive pili) gene were presented in different combinations. None
      strains contained shiga-like toxin (slt1) aswell as thermostable direct (tdh) and
      thermostable direct-related (trh) hemolysin genes of V. parahaemoliticus. On the
      model of infant rabbits almost all strains caused a significant enteropathogenic
      effect sometimes resembling cholera effect and in a number of cases dissemination
      of bacteria into various organs and tissues took place. Cultural supernatants of
      the majority of strains stipulated cell rounding in CHO cultures (one of them
      caused cell destruction) and disconnection of cells in McCoy and L-929 dense
      monolayers as well as increase of skin permeability in Craig's test. Conclusion.
      Apparently, diarrhea of different severity observed in patients from whom these
      strains were isolated as well as signs of virulence revealed in the laboratory
      models were determined by the expression of genes of accessory pathogenicity
      factors including those detected in the present study.

PMID- 18819405
TI  - [Expression of green fluorescent protein (GFP) gene of Aequorea victoria
      [correction of Aequoria victoria] in Lactobacillus plantarum bacterium ].
AB  - Results of development of shuttle expressing plasmid vector Escherichia coli
      Lactobacillus which allowed high level expression of heterologous genes in
      lactobacilli are represented. Vector pTRKH2 which is able to replicate in E. coli
      and in wide range of Gram-positive bacteria was used as the base. In order to
      provide high level of cloned gene expression constitutive-active synthetic
      promoter, site of initiation of translation, and terminator of transcription were
      introduced in the vector. Functional activity of this vector was confirmed using
      green fluorescent protein (GFP) gene from Aequoria victoria. Transformation of
      model strain by gfp gene-carrying plasmid resulted in appearance of typical
      fluorescent phenotype.

PMID- 18819406
TI  - [Situation on avian influenza caused by highly pathogenic influenza virus A/H5N1
      in countries of Asia, Africa, and Europe in 2007].

PMID- 18819407
TI  - [Molecular-epidemiologic characteristic of hepatitis A outbreak among workers of
      food stores network].
AB  - Investigation of hepatitis A (HA) outbreak developed in 2005 among workers of
      food stores networkwas performed using conventional epidemiologic diagnostics as
      well as methods of molecular epidemiology. In 14 of 15 ill persons, using
      polymerase chain reaction, HAV RNA was detected by PCR in serum obtained on 2 -
      25 day of illness (mean - 9.3 days). In 10 cases it was possible to determine
      nucleotide sequence of VP1/VP2 region of HAV genome and perform phylogenetic
      analysis of obtained isolates. It was determined that all isolates belonged to
      subgenotype IA, had high degree of homology and grouped in one cluster. These
      findings demonstrate their descendance from one source of infection, which, with
      high degree of probability, was the cook who made salads from fresh vegetables.
      HAV strain, which caused this epidemic outbreak circulates in Saint Petersburg
      for a long time and was already detected in 2004. Importance of vaccination
      against HA for persons working in manufacturing and distribution of food and use
      of molecular epidemiologic methods of surveillance for this infection is
      underlined.

PMID- 18819408
TI  - [Molecular and biologic characteristics of attenuated rubella viruses].
AB  - AIM: To study stability/variability of rubella virus vaccine strain "Orlov-B"
      during its adaptation to other tissue substrate. MATERIALS AND METHODS: Vaccine
      strains of rubella virus Wistar 27/3 and "Orlov-B" as well as wild type strains
      "Orlov-D" and "Lebedev" were used. Rhesus monkeys were used as laboratory
      animals. Standard virological, molecular and statistical methods were applied.
      RESULTS: Obtained as a result of adaptation to other tissue substrate - diploid
      human cell line M-22 - strain "Orlov-D" demonstrated stability on RCT40 sign in
      in vitro experiments. Comparative genotyping of "Orlov-B" and "Orlov-D" strains
      on gene E1 showed identity of nucleotide sequences of both variants. Genetic
      stability of virus on the gene coding the most immunogenic protein E1 was
      confirmed in vivo: the stable high immunogenic and protective activity of both
      "Orlov-B" and "Orlov- D" strains was demonstrated in experiments on rhesus
      macaques. CONCLUSION: New data on stability of attenuated rubella virus vaccine
      strains have practical significance for the development of new vaccines.

PMID- 18819409
TI  - [Influence of products of bacterial origin on the expression of surface molecules
      in monocyte-derived and endothelial cells].
AB  - AIM: To study the influence of lypopolysaccharide (LPS) of Gram-negative
      bacterium (Escherichia coli O55:B5) and lysate of Gram-positive bacteria
      (Streptococcus pyogenes - group A, type M1, strain 40/58) on the level of
      expression of important surface molecules of monocyte-derived cells from
      continuous cell line THP-1 and endothelial cells from continuous cell line EA.hy
      926. MATERIALS AND METHODS: Expression of surface molecules HLA-DR, CD11b, CD14,
      CD16, CD32, and CD54 was assessed using FITC- or PE-labeled monoclonal antibodies
      (Beckman Coulter, USA). Intensity of fluorescence was measured by flow cytometer
      Epics Altra manufactured by Beckman Coulter (USA). RESULTS: Studied components of
      Gram-positive and Gram-negative bacteria stimulated expression of CD14, CD16,
      CD32, and CD54 molecules on cells from THP-1 line; incubation of cells from EA.hy
      926 line in the presence of the same bacterial components increased expression
      levels of CD54 and HLA-DR molecules. CONCLUSION: Endothelial cells of EA.hy 926
      line was less sensitive to LPS of E. coli and lysate of S. pyogenes compared to
      monocyte-derived cells of THP-1 line. Usage of THP-1 cells allowed to reveal
      differences between effects of components of Gram-positive and Gram-negative
      bacteria. The stimulating effect of LPS was more pronounced compared to effect of
      S. pyogenes lysate in relation to expression of HLA-DR, CD11b, and CD54
      molecules, whereas lysate of S. pyogenes better stimulated expression of CD14,
      CD16, and CD32 molecules.

PMID- 18819410
TI  - [Role of innate immunity receptors in development of acute myocardial
      infarction].
AB  - AIM: To assess influence of toll-like receptors (TLR) ligands on the production
      of proinflammatory cytokine (TNFalpha) by peripheral blood mononuclear cells in
      patients with acute myocardial infarction (AMI). MATERIALS AND METHODS:
      Peripheral blood mononuclear cells (PBMC) obtained from 13 patients with AMI on
      1st and 14th day and from 17 healthy donors were stimulated by peptidoglycan,
      poly(I:C), lypopolysacchide, zimozan, flagellin and CpG oligodeoxynucleotides,
      which are ligands of TLR1/2, TLR3, TLR4, TLR2/6, TLR5 and TLR9 respectively.
      Spontaneous and induced by ligands production of TNFalpha was evaluated in
      supernatants of PBMC. RESULTS: Increased spontaneous production of TNFalpha by
      PBMC in patients with AIM was revealed on 1st day of the disease. Ligands of
      TLR2/6 and TLR4 demonstrated marked stimulatory effect on the production of
      TNFalpha by PBMC in patients with AMI compared with group of healthy subjects.
      CONCLUSION: Increased production of TNFalpha by PBMC in patients with AMI
      indicates the activation of TLR2 and TLR4 on PBMC. Hyperactivation of TLRs during
      acute pathologic conditions results in excessive production of proinflammatory
      cytokines, specifically TNFalpha, and can induce damage of cells and tissues
      involved in acute pathologic process.

PMID- 18819411
TI  - [Cytokine profile in mice with enhanced or depressed immune response to sheep
      erythrocytes induced by immunomodulator of bacterial origin--purified
      staphylococcal toxoid].
AB  - Influence of immunomodulator of bacterial origin - purified staphylococcal toxoid
      (PST) - on the synthesisof proinlammatory (IL-1beta, IL-6, TNFalpha, IFN-gamma)
      and anti-inflammatory (IL- 10) cytokines, as well as cytokines directing the
      immune response to Th1 (IL-12) or Th2 (IL-4) type was studied in mice. Serum
      cytokines levels as well as levels of cytokines produced by splenocytes
      spontaneously or after stimulation by phytohemagglutinin were measured 4 and 24
      hours after inoculation of PST. It was shown that PST in wide spectrum of doses
      (15; 1.5; 0.15 BU per mouse) was able to enhance or suppress synthesis of
      cytokines. Effect was nonlinear and its direction was depended from cytokine,
      time interval passed before obtaining the sample and dose of PST. For example, 15
      BU of PST enhanced whereas 0.15 BU of PST suppressed the IL-6 production 4 hours
      after inoculation. Decrease of IL-6 level in serum 24 hours after inoculation of
      PST was detected. Synthesis of several serum interleukins (IL-2, IL-10) did not
      changed 4 and 24 hours after inoculation irrespective from dose of PST. It was
      demonstrated that modulation of humoral immune response in vivo induced by PST
      did not associated with modulation of cytokine profile. For example, increase of
      number of cells secreting antibodies to sheep erythrocytes was registered both
      during increased synthesis of cytokines (4 hours, IL-1beta, IL-6, IL-12) and
      during period of its depression (IL-6, TNF-alpha, IFN-gamma), as well as during
      stable production of cytokines (IL-1beta, IL-6, IFN-gamma).

PMID- 18819412
TI  - [Development of enzyme-linked immunosorbent assay for detection of Mycoplasma
      pneumoniae antigens].
AB  - The variant of enzyme-linked immunosorbent assay (ELISA) for detection of
      Mycoplasma pneumoniae (Mp) antigens in sera of patients with respiratory
      infections was developed. Sensitivity of detection of soluble antigens of Mp in
      modeling experiment varied from 1.5 to 1.0 ng/ml (on protein). Approbation of the
      assay was performed using 50 serum samples obtained from patients with confirmed
      diagnosis of respiratory mycoplasmosis. In the ELISA test Mp antigens were
      detected in 96% of samples. Obtained results were confirmed by testing of these
      serum samples and isolated from them circulating immune complexes (CICs) in
      immunoblotting using polyclonal antibodies labeled by horse-radish peroxidase. Mp
      antigenswere detected both in free state and as components of CICs. Specific
      reaction was observed with proteins, which molecular mass varied from 30 to 170
      kDa (30, 37, 45, 56, 58, 72, 90, 130 and 170 (160) kDa). Obtained results point
      to appropriateness of use of developed assay for detection Mp antigens in sera of
      patients with respiratory infections.

PMID- 18819413
TI  - [Temperate Legionella bacteriophage: discovery and characteristics].
AB  - For the first time, temperate Legionella bacteriophage was isolated from organs
      of guinea pig infected with Philadelphia 1 strain of Legionella pneumophila.
      Negative colonies of bactriophage from 1.5 to 2.5 mm in diameter were detected.
      Central part of them was transparent and surrounded by peripheral zone of partial
      lysis. Electron microscopy showed that corpuscles of the phage consist from
      multifaceted elongated head of stretched hexagonal form and short tail. The
      bacteriophage lyzed bacteria, which cause Legionnaires' disease, and also had
      certain lytic activity against causative agent of tularemia.

PMID- 18819414
TI  - [Emergence of the integron-positive multi-drug resistant strain of Acinetobacter
      baumanii in Russian hospitals].
AB  - AIM: To detect the integron-positive strains among nosocomial Acinetobacter spp.
      and to determine their relationship on the genotype level. MATERIALS AND METHODS:
      Amplification by polymerase chain reaction using primers specific to sequences of
      the class 1 and 2 intergrons on the genomic DNA template followed by restriction
      fragments length polymorphism analysis as well as RAPD-genotyping of the integron
      positive strains were performed. RESULTS: Fact of spreading of Acinetobacter
      baumanii strain containing class 1 integron in medical centers was established.
      The composition of the integron's gene cassettes was analogous to worldwide
      (including epidemic) types. CONCLUSION: Molecular genetic analysis of the
      mobilized structures (integrons) under the standardization of used approaches are
      suitable for the surveillance for circulation of epidemic strains of nosocomial
      pathogens.

PMID- 18819415
TI  - [Using the pol gene sequence results in clinical practice and HIV epidemiology].
AB  - In order to detect mutations in protease and reverse transcriptase regions
      determining the resistance of human immunodeficiency virus (HIV) to
      antiretroviral drugs, sequencing of pol gene was used. Itwas concluded that HIV
      epidemic in Yamal region is characterized by heterogeneity of HIV-1 subtype
      population with trend to domination of recombinant and ground variants and
      spreading of mutant Mut-77 strain. Obtained results demonstrate the possibility
      of identification of mutations as epidemiological markers which permits their use
      for epidemiologic investigations.

PMID- 18819416
TI  - [Detection of infectious agents in heart valves during endocarditis using PCR
      technique].
AB  - Infectious endocarditis can be caused by various microorganisms. Diagnostics of
      local infection by microbiological methods is not always effective. For that
      reason we performed a study aimed for direct detection of potential infectious
      agents by polymerase chain reaction in patients' heart valve tissue. DNA of
      infectious agents was revealed in 72% of heart valve tissue samples from patients
      with septic endocarditis; in studied samples, along with bacterial DNA,
      herpesviruses' DNA was detected. Obtained results confirm the presence of
      infection, which allows to perform specific diagnostics of infectious
      complications after implantation of prosthetic cardiac valves.

PMID- 18819417
TI  - [Epizootic situation and measures for control of wild animals' rabies in Republic
      of Bashkortostan].
AB  - Epizootologic characteristics of rabies incidence in the Republic of
      Bashkortostan for the period 1998 - 2006 are presented. Districts of
      Bashkortostan are divided on 3 zones according to severity of epizootic
      situation. Three years-cyclicity of rabies incidence with peak during winter was
      determined. Foxes, raccoons, wolves, lynxes, badgers, minks and, during recent
      years, corsacs are involved into the epizootic chain. Main source of rabies in
      the Republic is foxes with share of 91.9% among sick wild animals. During 1999
      2006 8 cases of hydrophobia were registered. Results of analysis of effectiveness
      of oral immunization and regulation of wild fauna population are presented.

PMID- 18819418
TI  - [Assessment of the lakes' trophy levels].
AB  - AIM: To develop a method for assessment of lakes' trophy level combining
      acceptable levels of precision, complexity, and universality. MATERIALS AND
      METHODS: Initial data on dynamics of qualitative and quantitative parameters of
      phytoplankton development, as well as meteorological and hydrochemical data
      obtained during comparative observation of two floodplane lakes of the Ural
      river, which differed on level of anthropogenic burden, were used in the study.
      RESULTS: Information value of biotic and abiotic parameters for determination of
      floodplane basins' trophy level was established. By using regression analysis,
      mathematical model was developed which can determine the trophy level of lake
      type basins with probability 86.5%. Advantage of this method is minimization of
      quantityof parameters used forbuilding of mathematical model suitable for
      determination and forecasting of lakes' trophy level. CONCLUSION: Developed
      method was tested on the lakes in steppe Ural area. The method is handy and has
      high level of validity. It can be used during monitoring for assessment of
      ecologic and hygienic state of a lake for answering the question about its
      practical use.

PMID- 18819419
TI  - [Role of pathogenicity factors of Staphylococcus aureus in development of atopic
      dermatitis].
AB  - Factors of pathogenicity of staphylocci and their key role in pathologic process
      are discussed. Staphylococcus aureus is the leading etiological agent infecting
      skin of the patients with atopic dermatitis. Development of atopic eczema in
      patients infected by Staphylococcus aureus is in much determined by wide spectrum
      of virulence factors inherent to this type of staphylococci. Among those, the
      more important are proteinases, destroying antimicrobial peptides of derma,
      toxins, superantigens, which can cause and support of inflammatory reaction in
      derma during this disease. It was specially noted that pathogenicity factors
      should be studied as complex system, which formed as a result of long joint
      evolution of opportunistic microflora and immune system of the host.

PMID- 18819420
TI  - [Modern methods of laboratory diagnostics of Chlamydia infections].
AB  - Need for further improvement of methods for verification of etiological agent of
      urogenital and respiratory chlamydiosis on the basis of increased
      biotechnological requirements to antigens for serological reactions, primers for
      PCR assay (refinement of connection of primers with microorganism's zones of
      genome most significant for its life activity or formation of most diagnostically
      significant complexes of primers), and selection of cultivating conditions
      considering the predicted features of clinical strains of the agent was
      substantiated.

PMID- 18819421
TI  - [Role of Yersinia pestis biofilms in mechanisms of plague enzootics].

PMID- 18819422
TI  - [Hepatic cell transformation changes in experimental opisthorchiasis].
AB  - Changes in the liver where Opisthorchis felines (Rivolta, 1884) parasitizes were
      traced by light and transmission electron microscopies on experimental models
      (gold hamsters) of acute and chronic opisthorchiasis. Regenerative processes,
      such as hepatic epithelial mitotic indices, binucleated, hypertrophic
      hepatocytes, were determined; the composition of infiltrates was identified;
      fibroplastic changes and hepatocytic apoptotic index were traced. The
      progression/regression (P/R) ratio was used to detect atrophy of a hepatic
      parenchymatous component (hepatocytes) in different periods (from 3 to 120 days)
      of invasion. In opisthorchiasis, proliferation of committed hepatocytes was first
      found on day 10 of invasion. Oval (committed) cells are differentiated mainly to
      cholangiocytes, followed by the formation of ductular structures; the committed
      cells of the liver may be simultaneously a source of programmed hepatocellular
      differentiation; however, the newly formed hepatocytes are solitary amongst them
      in opisthorchiasis.

PMID- 18819423
TI  - [Dysregulation of cooperative interactions of immunocytes and eosinophils in the
      mechanism of development of eosinophilia in Opisthorhis felineus invasion].
AB  - The authors studied the levels of mononuclear cell production of eosinophil
      specific cytokines (IL-3, IL-5), the serum levels of eotaxin by enzyme
      immunoassay; the expression of the eosinophilic cell receptor apparatus by flow
      cytofluorometry in patients with acute and chronic Opisthorchis invasion.
      Eosinophilia-associated Opisthorchis invasion was found to be accompanied by a
      pronounced change in the serum production of the key cytokine regulators of
      eosinophilic homeostasis (elevated IL-3 and IL-5 levels) and eotaxin by
      peripheral blood mononuclear leukocytes. There was an increase in the number of
      receptor structures to eosinophil-specific cytokines (IL-5R-, IL-3R-, and CCR3
      positive cells) in patients with opisthorchiasis. In vitro incubation of the
      eosinophils, obtained from patients with opisthorchiasis, with the recombinant
      forms of cytokines (IL-5, IL-3, and eotaxin) demonstrated the decreased
      expression of IL-5 and IL-3 receptors with the normal presentation of CCR3. With
      the developed acute helminthiasis, the revealed changes were more pronounced than
      those observed in chronic Opisthorchis invasion.

PMID- 18819424
TI  - [Associations of the genotypes of the CYP1A1 gene with predisposition to hydatid
      disease caused by Echinococcus granulosus strain G1].
AB  - DNA samples isolated from peripheral venous blood lymphocytes in 73 children with
      hydatid disease were studied. The polymorphism of exon 7 (A4889G) of the CYP1A1
      gene was analyzed by polymerase chain reaction, followed by hydrolysis with
      restriction endonuclease HincII. The material for E. granulosus genotypes to be
      studied was obtained from the germinal layer of larvocysts. The fragment of the
      mitochondrial gene encoding for the first subunit of cytochome-C-oxidase was as a
      DNA marker. The amplified E. granulosus DNA fragments underwent direct sequencing
      and a genotype was identified. The findings have led to the conclusion that
      carriage of polymorphic allele Val of exon 7 (A4889G) of the CYP1A1 gene in those
      infested with E. granulosus genotype G1 (common, sheep strain) is a risk factor
      of the development of the clinical form of echinococcosis granulosus.

PMID- 18819425
TI  - [Informative value of methods for laboratory diagnosis of Giardia infection].
AB  - The author assesses the informative value of two methods of laboratory diagnosis
      of L. intestinalis: serological assay using indirect immunofluorescence versus
      fecal Giardia antigen test using the immunochromatographic RIDA Quick Giardia
      test system. The results of these procedures were compared with those of fecal
      microscopy. The serological approach to diagnosing Giardia infection was found to
      be of low informative value. There is evidence suggesting the high specificity
      and sensitivity of detection of Giardia antibody in the feces, which allows it to
      be recommended in parasitological laboratory. It has been established that fecal
      prestorage in the Turdyev preservative can reduce the sensitivity of the RIDA
      Quick Giardia test system at the low concentration of parasitic cysts in the
      material being examined.

PMID- 18819426
TI  - [Malaria mosquitoes of the Anopheles maculipennis (Diptera, Culicidae) complex in
      Georgia].
AB  - Malaria mosquito larvae and imagoes underwent morphological, cytogenetic, and
      molecular genetic analyses in West and East Georgia. In the areas under study,
      the authors identified three related types of malaria mosquitoes of the
      maculipennis complex: An. maculipennis Meigen, 1818; An. melanoon Hacket, 1934;
      An. sacharovi Favre, 1903. The authors revealed the types An. maculipennis and
      An. melanoon in the Kolkhida cavity (West Georgia) and An. maculipennis and An.
      sacharovi in the Iveria cavity (East Georgia). The morphology of eggs was defined
      in the study types of mosquitoes. An. melanoon ovipositions similar in the
      exochorion pattern with An. messeae eggs were found in West Georgia.

PMID- 18819427
TI  - [African trypanosomiasis in the Republic of Guinea].
AB  - The information on the Gambian form of African human trypanosomiasis (AHT),
      collected in Guinea, is analyzed. The fauna of tsetse flies currently numbers at
      least 8 species. Two species are the vectors of AHT. These include G.(N.)
      palpalis and G.(N.) tachinoides, the latter of which is the vector of animal
      trypanosomiasis ("nagana" cattle disease) as well. In the period of 1991 to 1997,
      the country's incidence of AHT was 9.6:100,000. The highest morbidity was
      established in the natural region of Lower Guinea (23.4:100,000, with mortality
      rates of 1.1 to 18.5%). A clinical study of the population of a few villages in
      this region revealed 6 patients with AHT. Its clinical diagnosis was
      parasitologically verified. Preliminary studies suggest the circulation of the
      pathogen of AHT in Guinea, the most active foci of which are in Lower Guinea. The
      epidemiological features of AHT and its epidemic significance for Guinea are yet
      to be studied.

PMID- 18819428
TI  - [First evidence for breeding Aedes aegypti L in the area of Greater Sochi and in
      some towns of Abkhasia].
AB  - A preliminary survey of some widely spaced settlements in Greater Sochi (and in
      the city of Sochi) in a period of late July to early October 2007 has revealed
      man-biting females and swarming males of Aedes aegypti females indoors and
      outdoors. Man-biting Ae. aegypti females, like males swarming nearby, were also
      present in the town of Gudauta under study in September (the males and females of
      this species were found on one-day youngsters in the animal houses) and in the
      suburbs of the town of Sukhumi (Republic of Abkhazia). Ae. aegypti breeding
      places and larvae were revealed at the back of houses in Gudauta. Detection of
      not only males, but also females and preimagoes of this species suggests that a
      local breeding Ae. aegypti population is available in this area. The findings
      show that a local breeding population of Ae. aegypti mosquitoes has reemerged in
      the inspected area of the Black Sea coast (Tuapse-Sukhumi) with a humid
      Mediterranean climate after 35-40-year absence. Prevention of outbreaks of
      menacing human arbovirus diseases in the importation of their pathogens to the
      health resort-tourist area of the Caucasian Black-Sea coast requires urgent
      organization of a continuous entomological service for environmental monitoring,
      organization, and implementation of measures to eradicate Ae. aegypti.

PMID- 18819429
TI  - [Epidemiological aspects of infectious diseases during international migration of
      the population].

PMID- 18819430
TI  - [Experience in sanitizing an urban focus of vivax malaria (Tashkumyr,
      Kyrghyzstan)].

PMID- 18819431
TI  - [Gastrodiscoidosis is a dangerous zoonosis].
AB  - The paper gives data on the helminthiasis--gastrodiscoidosis, a zoonotic disease
      caused by the trematode Gastrodiscoides hominis (Lewis et McConnall, 1876)
      parasitizing in the animal and human intestine in the endemic foci of both Russia
      and foreign countries. It also presents information on the morphology of the
      helminth, the biological cycle of development of the parasite and its habitat and
      spread, as well as its induced abnormalities and on the method of diagnosing of
      the disease.

PMID- 18819432
TI  - [Expression of mRNA for corticoliberin and vasopressin in hypothalamus and
      amygdala on the background of administration of psychoactive drugs in rats].
AB  - Wistar male rats were injected intraperitoneally for 4 days in elevated doses
      with: (1) physiological saline (control; 0.1 - 0.2 - 0.4 - 0.8 ml/rat), (2)
      amphetamine (0.5 - 1.0 - 2.0 - 4.0 mg/kg); (3) fentanyl (0.00625 - 0.0125 - 0.025
      - 0.05 mg/kg), (4) 40% aqueous ethanol solution (0.5 - 1.0 - 2.0 - 4.0 g/kg), (5)
      ethaminal sodium (2.5 - 5 - 10 - 20 mg/kg), and (6) dexamethasone (0.5 - 1.0 -
      2.0 - 4.0 mg/kg). The forced regime of drug administration led to gradual load of
      the organism and prevented drug tolerance development. This method is widely used
      for the formation of drug dependence (or its features) due to various narcotic
      agents. The maximum level of mRNA expression for corticoliberin was registered in
      amygdala after the administration of dexamethasone (0.46 units compared to beta
      actin), and the minimum level was observed after treatment with sodium ethaminal
      (0.07) and fentanyl (0.037). In hypothalamus, sodium ethaminal produced elevated
      mRNA expression (0.8 units), followed by ethanol (0.37) and fentanyl (0.039).
      Amphetamine activated mRNA expression for corticoliberin neither in hypothalamus
      nor in amygdala for all of the drugs studied. The mRNA expression for vasopressin
      was also not registered for all drugs in hypothalamus and amygdala. Therefore,
      the reinforcing system of hypothalamus supports the typical reaction on the
      administration of narcotic agents, while the extended amygdala system includes
      both the proper reinforcement and the stress reactivity elements.

PMID- 18819433
TI  - [Interstrain differences in the content of excitatory and inhibitory amino acids
      in the brain of DBA/2J, Balb/c and C57BL/6 mice: characteristics of the effect of
      a dipeptide antipsychotic drug dilept].
AB  - We have performed a comparative study of the content of glutamate (Glu),
      aspartate (Asp), taurine (Tau), glycine (Gly) and gamma-amino-butyric acid (GABA)
      in the cortex, hippocampus, and striatum of the DBA/2J, Balb/c and C57BL/6 mice
      brain. The levels of Glu, Tau and GABA in DBA/2J hippocampus was lower than those
      in other experimental strains. These findings are consistent with published data
      on the specific neurophysiological properties of DBA/2J (neuroleptic sensitive
      prepulse inhibition, deficit), thus allowing this strain to be used in modeling
      schizophrenia. Taking into account these facts, in the next step we investigated
      the effects of dilept, the new neurotensine-derived dipeptide with antipsychotic
      activity (GZR-123, methyl ester of N-caproyl-L-prolyltyrosine), on the content of
      neurotransmitter acids in DBA/2J mice brain structures. In a dose of 0.8 mg/kg
      (i.p.) dilept induced a statistically significant increase in the levels of Glu,
      Tau and GABA in striatum of DBA/2J, as well as insignificant increase in the
      levels of these amino acids in the cortex. These effects are quite similar to
      those described for the parent peptide neurotensine, in case of its intracerebral
      administration. The results of our study prove the necessity of the further
      development of dilept as a potential antipsychotic drug.

PMID- 18819434
TI  - [Sexual distinctions of the diazepam activity in rats in the conflict situation].
AB  - Diazepam caused less pronounced shifts in the conflict situation test in female
      rats as compared to males. The drug produced more pronounced anticonflict action
      on male rats in the evening. In female rats, a doze of 0.5 mg/kg of the
      anxiolytic drug produced a clear anticonflict action, mostly in the evening;
      however, even this effect was approximately only about half of that observed in
      males in the same period of time.

PMID- 18819435
TI  - [Blockade of the alpha3alpha4 N-cholinoreceptors and GluR1 AMPA receptors
      eliminates clonic-tonic nicotinic and kainate seizures].
AB  - Monoammonium N-alkyl derivative of decylamine (IEM-1678), which blocks
      alpha3beta4 N-cholinoreceptors (but does not block GluR1 AMPA receptors), in
      doses of 1.0 - 3.0 mg/kg produces a 4-fold decrease in the frequency and
      lethality of nicotinic clonic-tonic seizures. However, even in the maximum dose
      of 3 mg/kg, IEM-1678 only slightly decreases kainate clonic-tonic seizures. Bis
      ammonium compound IEM-1460 (containing adamantyl radical), which blocks both
      GluR1 AMPA receptors and alpha3beta4 N-cholinoreceptors, in a range of doses 0.1 
      3 mg/kg produces a 5- to 8-fold decrease in the frequency and virtually
      completely eliminates lethality of both clonic-tonic nicotinic and kainate
      seizures. Hence, the complete elimination of generalized kainate and nicotinic
      seizures requires combined blockade GluR1 AMPA and alpha3beta4 N
      cholinoreceptors.

PMID- 18819436
TI  - [Characteristics of ladasten effect in neurasthenia patients with various EEG
      parameters].
AB  - Clinical and electroencephalographic (EEG) analysis ofladasten action in anxiety
      asthenic patients with respect to their EEG-defined individual typological
      characteristics was carried out. Primary psychopathologic disorders and ladasten
      effects were assessed by objective classification methods (factor and cluster
      analyses), and individual EEG types characterized by marked or reduced alpha
      rhythm were determined. No significant correlations between baseline EEG results
      and the initial mental condition indices were found. Significant differences
      ofladasten action in patients with different EEG types were found. It was
      established that, in patients with marked alpha rhythm corresponding to asthenic
      personal traits, ladasten exhibits predominantly a psychostimulant action
      assessed by clinical rating scales, which is accompanied by high frequencies of
      alpha rhythm increase and beta 1 and beta 2 rhythms decrease. In patients with
      reduced alpha rhythm and the EEG type corresponding to asthenic personal traits,
      ladasten action was characterized by an increase of alpha-rhythm low frequencies
      and the opposite reaction of beta 1 and beta 2 rhythms, whose are typical for the
      EEG pattern of anxiolytic effect. These results may indicate that the effect of
      ladasten depends on the initial brain activity level, which varies in patients
      with different individual typological traits.

PMID- 18819437
TI  - [Cerebrovascular and antiaggregative effects of GABA-docosahexaenoyldopamine
      conjugate].
AB  - The effects of GABA - docosahexaenoyldopamine (DHED) conjugate on the cerebral
      haemodynamics and thrombocyte aggregation were evaluated and compared to these of
      docosahexaenoyldopamine alone. The GABA - DHED conjugate was shown to
      significantly enhance the cerebral circulation in rats with a model of global
      transient cerebral ischemia, as compared to the intact animals. Administered
      alone, DHED increased the blood supply of both intact and ischemic brains to an
      equal extent. The GABA-DHED conjugate demonstrated the antiaggregative activity,
      but the effect was less expressed than that of DHED alone.

PMID- 18819438
TI  - [Anticoagulant activity of arabinogalactane sulfate and cedar bark extract
      studied in vitro].
AB  - We have studied in vitro the ability of the Siberian cedar crust (SCC) extract
      (Pinus sibirica Du Tour) and arabinogalactan sulphate (AGS) extracted from wood
      of Siberiam pine-tree (Larix sibirica Ledeb.) to increase the human blood plasma
      coagulation time and also to inhibit the amydolytic activity of thrombin (aIIa)
      and the coagulation factor Xa (aXa). A method has been developed by means of
      which SCC increases the aXa activity by a factor of 3.7 and the aIIa activity by
      a factor of 2.5. The AGS preparation increased the blood plasma coagulation time
      in the test for activated partial thromboplastin time. An effective
      concentration, at which the time of plasma coagulation was increased by a factor
      of 2 (in comparison to the control) was 2.94 +/- 0.33 mg/ml. AGS did not exhibit
      the ability to inhibit the Xa activity.

PMID- 18819439
TI  - [Effect of some organic and inorganic magnesium salts on lipoprotein state in
      rats fed with magnesium-deficient diet].
AB  - Low serum magnesium (Mg) concentrations have been reported in patients with
      atherosclerosis. From the other hand numerous clinical reports suggest the
      beneficial effects of Mg adjuvant therapy for the treatment of atherosclerosis.
      The purpose of this present study was to compare the effect of Mg L-aspartate and
      Mg chloride alone and in combinations with pyridoxine, Mg sulfate and Magne B6
      (Mg lactate with pyridoxine) on lipid profile in rats fed with Mg deficient diet.
      To induce hypomagnesemia, fifty-three rats were placed on a Mg-deficient diet
      (ICN Biomedicals Inc. Aurora, OH) and demineralized water for 7 weeks. Seven
      control rats were fed a basal control diet (Mg content = 500 mg/kg) and water
      (with Mg content 20 mg/l) for equal duration. On the forty-ninth day of Mg
      deficient diet, rats were treated one of the six supplementations: Mg chloride,
      Mg L-aspartate alone and in combinations with pyridoxine, Mg sulphate and Magne
      B6 (50 mg Mg and 5 mg vitamin B6 per kg). In our study Mg deficiency resulted in
      increase of triglyceride (by 35.2 %p < 0.0001), LDL (more than fourfold p <
      0.0001), total cholesterol (by 38.7% p < 0.0001), apolipoprotein B (by 74.1%, p =
      0.0006) levels and decrease in concentration of HDL (by 28.7% p < 0.0001). The
      non-HDL cholesterol/HDL cholesterol ratio was more than threefold increased (p <
      0.0001). Oral magnesium salts led to normalization of lipid state with a return
      to pre-deficient levels. Magnesium salts in combinations with pyridoxine tended
      to be significantly more effective as compared with salts without pyridoxine. The
      hypolipidemic effect of studied salts was comparable with those observed in Magne
      B6 treatment and significantly higher than in magnesium sulfate treatment.

PMID- 18819440
TI  - [Preclinical investigation of Mn(II)-diethylenetriaminepentaacetate
      (Mangapentetate) as paramagnetic contrast agent for magnetic resonance
      tomography].
AB  - The preclinical evaluation of 0.5 M solution of a manganese(II)-DTPA complex
      (Mangapentetate, Pentamang) has been carried out in order to test the ability of
      manganese to be used as substitute for potentially toxic gadolinium in
      paramagnetic contrast agents in the MRI clinical routines. The toxicologic tests
      of the Mn(II) - DTPA were carried out in mice, rats, and rabbits. Liquid phantoms
      served for direct comparison of the ability of Mn(II) - DTPA to increase the
      intensity of T1-weighted SE-images to the contrast properties of the Gd(III) -
      DTPA (Magnevist). Normal healthy rabbits (n = 12) were used for quantification of
      the imaging ability of Mn(II) - DTPA. The value of LD50 in rabbits was above 10
      ml/kg, rather close to that one of Gd(III) - DTPA. An increase in intensity of
      the T1-weighted images induced by addition of Mn(II) - DTPA in phantom tests did
      not differ significantly from the values obtained with Gadopentetate. Mn(II) -
      DTPA delivered prominent enhancement of normal kidneys in healthy rabbits as well
      as chest tumors in dogs.

PMID- 18819441
TI  - [Preclinical toxicological evaluation of Pentamang and Mangascan].
AB  - We have carried out a preclinical toxicological investigation (acute toxicity
      evaluation) of Mangascan (0.5 M solution of manganese(II) - EDTA complex) and
      Pentamang (0.5 M solution of manganese(II) - DTPA complex), a new paramagnetic
      contrast agents for MRI procedures. In 14 days after single intravenous
      introduction of Mangascan (10.0 ml/kg) or Pentamang (5.0 ml/kg) to rats, no any
      toxic influence of the studied agents was detected in the general condition, bone
      marrow, cardiovascular and central nervous systems, and liver and kidney
      functions of experimental animals. No pathological changes were observed in the
      functional activity and morphology of the internal organs and systems. The
      results showed that both Mangascan and Pentamang belong to the class of low
      toxicity substances.

PMID- 18819442
TI  - [The first and only one beyond Urals].

PMID- 18819443
TI  - [Ginkgo Biloba as a cognitive enhancer].
AB  - Ginkgo Biloba preparations exhibit nootropic activity in the absence of side
      effects, which is confirmed by numerous experimental observations and clinical
      results. The neuroprotector effect of these drugs is based on the antitoxicant
      action, antioxidant properties, and the ability to normalize the neuromediator
      and energy transfer mechanisms in cerebral neurons. In this review, recent data
      on the influence of various Ginkgo Biloba preparations on the cognitive functions
      in animals and humans and neurochemical mechanisms of the nootropic effect are
      summarized.

PMID- 18819444
TI  - [Pharmacoepidemiology of epilepsy].
AB  - The lecture presents the history of the pharmacotherapy of epilepsy and analyzes
      the current situation at the pharmaceutical market related to the appearance of
      new, high-cost antiepileptic drugs in recent decades. The lecture substantiates
      the need of pharmacoepidemiology studies for the objective assessment of
      efficacy, safety and economical impact of new antiepileptics, especially in
      children, taking into account limited randomized preclinical trials in this group
      of patients. The lecture describes the role of pharmacoepidemiology in
      supplementing the findings of randomized controlled trials with new real-life
      evidence, in quantitative evaluation of adverse reactions, and in discovery of
      new adverse effects, as well as in the development of cost-effective strategies
      for rational antiepileptic therapy of children and in the overall improvement of
      public health economics.

PMID- 18819445
TI  - [Studies on the possible application of molecular methods in diagnosing carriers
      and in similarity analysis of group B streptococci (Streptococcus agalactiae)].
AB  - The most popular method of GBS identification in Poland currently is by culturing
      on enriched agar and verifying the Lancefield Group using special latex
      agglutination kits. However, the classical methods are time-consuming and their
      sensitivity is insufficient therefore it is becoming more common to try and apply
      molecular methods which are characterized by high sensitivity and rapid results.
      Moreover, molecular methods give us the possibility to carry out epidemiological
      investigations and gene detection, for instance for antibiotic resistance. It was
      confirmed that PCR and FISH procedures may be effective in rapid detection of
      GBS. Thanks to RAPD methods we showed that newborns born to colonized mothers
      were colonized by GBS strains which originated from the mother, irrespective of
      the way and the course of labour. Additionally, we detected GBS colonization in
      children who were born to mothers who were not colonized by GBS. These children
      were probably colonized with strains coming from hospital environment. More
      studies are needed to elucidate the route of transmission and the role of
      colonization of the medical staff. Using multiplex PCR we showed the presence of
      ermA, ermB and ermC genes in phenotypically confirmed MLS, GBS strains.

PMID- 18819446
TI  - [Infectivityand resistance to antibiotics of non-fermentative rods isolated from
      patients hospitalised in pediatric center of Lower Silesia in Wroclaw in the
      years 2000-2006].
AB  - The aim of this study was to evaluate the frequency of isolation and
      antimicrobial resistance testing of non-fermentative rods isolated from clinical
      specimens from patients hospitalized in Korczak Pediatric Center of Lower Silesia
      in Wroclaw. The susceptibility of bacteria to selected antibiotics was
      determined. The commonest pathogens were Pseudomonas rods (81.8%) isolated from
      respiratory system and urine of patients hospitalized in unit intensive care.
      Variety of resistance patterns were detected in bacteria. ESBL were detected the
      most of S. maltophilia. Strains of Pseudomonas and Acinetobacter resistant to
      carbapenems were detected with a frequency of 5.5% and 35.9%.

PMID- 18819447
TI  - [Antibiotic susceptibility and occurrence of ESBL, IBL and MBL in Pseudomonas
      aeruginosa strains].
AB  - The aim of this study was to evaluate the drug susceptibility of P. aeruginosa
      strains and to detect strains producing inducible beta-lactamases (IBL), extended
      spectrum beta-lactamases (ESBL), and metallo-beta-lactamases (MBL). During 6
      month (October 2005 - March 2006), 66 strains of P. aeruginosa strains were
      cultured from clinical specimens obtained from patients of two of hospitals in
      Siedlce and from patients of outpatient clinics. All the strains were identified
      in the automatic ATB (bio Merieux). The susceptibility of bacteria to antibiotics
      was tested by standard disc diffusion method. The majority of strains were
      susceptible to meropenem (89.4%), piperacillin combined with tazobactam (84.8%),
      ciprofloxacin (84.8%) and piperacillin (83.3%). Many of our strains were
      resistant to carbenicillin (69.7%), mezlocillin (45.5%), gentamicin (42.4%) and
      netylmicin (30.3%). 6 strains (9.1%) were multidrug-resistant (MDR). Inducible
      beta-lactamases were detected with the use double disc method according to
      Sanders and Sanders. ESBL-producing strains were detected with double disc test
      (DDST) according to Jarlier et al. These strains were identified as ESBL-positive
      on the basis of the DDST were also determined using a double disc (DD) test
      according to Appleton. Production of metallo-beta-lactamases (MBL) was examined
      with the use of Etest MBL (AB Biodisk, Sweden) and the double disc test according
      to Arakava et al. Sixty-five IBL-producing strains (98.5% of all strains) and
      three strains (4.5%) with MBL activity were detected. Strains producing extended
      beta-lactamases (ESBL) were not found.

PMID- 18819448
TI  - [Evaluation of antigenic properties of Campylobacter jejuni and Campylobacter
      coli proteins in a western-immunoblot].
AB  - Campylobacter jejuni and Campylobacter coli are the most common bacterial cause
      for acute diarrheal illnesses in developed countries. The aim of this study was
      to evaluate the antigenic properties of Campylobacterjejuni and Campylobacter
      coli proteins in western-blot assay. Whole-cell components of Campulobacter
      jejuni and Campylobacter coli were separated by sodium dodecyl sulfate
      polyacrylamide gel electroforesis. Using this method we detected in all seven C.
      jejuni strains 21 peptides migrating between 180-29 kDa. All three Ccoli strains
      had a 17 bands migrating with the same molecular weight range. Proteins were
      transferred electrophoretically to nitrocellulose paper for immunoblotting
      experiments. The 74 kDa protein reacted strongly in all classes ofimmmunoglobulin
      with all tested human serum samples. We observed that this protein reacted also
      with human immunoglobulins for Salmonella and Yersinia sp. This cross-reaction
      observed for this protein could give false positive results in routine diagnosis
      of C. jejuni infections. The proteins with molecular weight of: 92, 62, 56, 52,
      45-43, 29 kDa were most recognized in the 20 human serum samples. The other
      proteins of Cljejuni and C. coli, particularly in the 68-50 kDa and 45-31 kDa
      regions, were recognized occasionally and the response to these in reconvalescent
      sera was usually weak. The result of this study showed that the proteins with
      molecular weight: 92, 62, 56, 52, 45-43 and 29 kDa can be use in routine
      serological diagnostic of campylobacteriosis.

PMID- 18819449
TI  - [Influence of the fluoride releasing dental materials on the bacterial flora of
      dental plaque].
AB  - The assessment of influence of silver-free, fluor releasing dental materials on
      dental plaque bacteria quantity. 17 patients were included into the study. 51
      restorations were placed following manufacturers recommendations. Following
      materials were used: conventional glassionomer Ketac-Molar ESPE, resin modified
      glassionomer Fuji II LC GC and fluor containing composite Charisma Heraeus Kulzer
      Class V restorations were placed in following teeth of upper and lower jaw:
      canines, first bicuspids, second bicuspids. Sound enamel was a control. After 10
      weeks the 72 hours old dental plaque was collected from surface of restorations
      and control using sterile probe. Total amount of 68 dental plaques were
      investigated. Each plaque was placed on scaled and sterile aluminum foil. The
      moist weight of dental plaque was scaled. Dental plaque was moved into 7 ml 0.85%
      NaCl solution reduced by cystein chlorine hydrogen and disintegrated by
      ultrasounds (power:100 Watt, wave amplitude: 5 micorm). The suspension of dental
      plaque was serially diluted from 10(-4) to 10(-5) in sterile 0,85% NaCl solution,
      and seeded with amount of 0.1 ml on appropriate base. In dental plaque trials the
      amount of cariogenic bacteria was calculated--Streptococcus mutans,
      Streptococcus, Lactobacillus, Veillonella and Neisseria, and also total amount of
      aerobic and anaerobic bacteria was measured. Microbiologic studies were performed
      in Institute of Microbiology, Medical University, Lodz. Statistical analysis of
      collected data was accomplished. In 72 hours old dental plaques collected from
      the surfaces of Ketac -Molar, Fuji II LC, Charisma after 10 weeks since being
      placed into the class V cavity, results show no statistically significant
      differences in the amount of Streptococcus mutans, Streptococcus spp.,
      Lactobacillus spp., Veillonella spp., Neisseria spp, in total amount of aerobic
      and anaerobic bacteria and in the quantity proportion of Streptococcus mutans
      versus Streptococcus spp. in comparison with control trail. Results show no
      statistically significant differences in the amount of listed above bacteria and
      in the proportion of Streptococcus mutans versus Streptococcus spp. in 72 hours
      old dental plaques collected from surfaces of investigated restorative materials.

PMID- 18819450
TI  - [Elaboration of PCR MP diagnostic kit for genetic typing of bacterial strains].
AB  - The rules of diagnostic kit elaboration for genetic typing of microorganisms,
      designed for epidemiological studies, have been shown in this paper. PCR MP
      method has been used for diagnostic kit elaboration. Well defined
      epidemiologically Enterococcus faecium strains have been applied as a research
      model. The optimisation of the method has been carried out using different amount
      of reagents and time of the particular stages. Critical parameters, which have
      significant influence on the quality of obtained results, have been assigned.
      Optimalised procedure, named PCR MP unique, has been validated for genetic typing
      of different species of microorganisms and its potential application for routine
      epidemiological studies. The PCR MP method has been successfully used for
      elaboration of diagnostic PCR MP unique-KIT, which allows intra-species
      differentiation of bacterial strains. The PCR MP unique-KIT enables fast, easy
      and cheap analysis of strains, using elementary laboratory equipment--gradient
      thermocycler.

PMID- 18819451
TI  - [Comparison of quantitative methods of DNA CMV investigation in clinical samples
      obtained from symptomatic and asymptomatic patients undergo renal
      transplantation].
AB  - Cytomegalovirus infection is one of the main problem in immunocompromised
      patiens. Quantitative assessment of CMV load (viral load), rate of increase of
      load and determination of DNA level above which the likelihood of disease is high
      (viral load thresholdfor disease) have significant prognostic and therapeutic
      importance at transplant recipients. The aim of this work was the comparison of 3
      quantitative molecular techniques and assessment the threshold for disease for
      each of them. The study was undertaken with 37 samples of serum and the whole
      from 17 renal transplant recipients. Part of samples (n=16) comes from
      symptomatic patients, and were taken in period of clinical symptoms
      demonstration. The samples ware investigated by hybridization method (HC)
      performed accordingly to Hybrid the Capture procedure, (r-t PCR) Amplicor test
      (COBAS AMPLICOR CMV the Monitor test) nd real time PCR (r-t PCR). In 21 out of 37
      samples DNA CMV was detected by all 3 methods, 2 samples gave concordant negative
      results. The CMV DNA level measured by all 3 methods was significantly higher (p
      < 0.05; t-Student test) in samples from symptomatic patients than from
      asymptomatic: 4.79 versus 3.58 for HC; 3.06 versus 1.36 for PCR-Amplicor and 4.23
      versus 2.88 log DNA copies/ml for r-t PCR. The threshold for disease connected
      with high likelihood of disease (p < 0.05; Fisher test) was established at 4 log
      for r-t PCR method, 4,61 for hybridization and 3 log DNA CMV copies/ml for PCR
      Amplicor.

PMID- 18819452
TI  - [In vitro acyclovir and cidofovir susceptibilities of human herpesvirus type 1
      clinical isolates].
AB  - Infections with human herpesviruses types 1 and 2 (HHV-1 and HHV-2) are common
      worldwide and cause a wide range of signs and symptoms. Antiviral drugs, in
      particular aciclovir are used in therapy of herpetic infections. The aim of the
      study was determination of susceptibilities of HHV-1 isolates (n+46) for
      antiviral drugs (acyclovir and cidofovir) in vitro. Swabs taken from different
      lesions were used for infection of Vero cells and cythopathic effect was
      observed. Viruses from cell cultures with positive CPE were later identified with
      in-house PCR and efficacy of acyclovir and cidofovir in HHV-1 infected Vero cell
      monolayer cultures was tested by the yield reduction assay. Obtained data
      indicate, that aciclovir ID50 average value for HHV-1 clinical isolates was 0.74
      microg/ml--the value about 10% greater then described in literature. Similarly in
      vitro analysis of sensitivity of viruses for cidofovir, shows that concentrating
      is over ten-fold higher in comparison for aciclovir.

PMID- 18819453
TI  - [Plasma fibronectin in pregnancy complicated by diabetes mellitus and
      preeclampsia].
AB  - OBJECTIVES: The aim of this study was to evaluate concentration of plasma
      fibronectin (FN) in course of pregnancy complicated by preeclampsia accompanied
      by diabetes mellitus and to assess whether the concentration of FN depends on the
      state of carbohydrate metabolism. MATERIAL AND METHODS: The study was carried out
      in 2 groups: group K--consisting of 35 healthy pregnant women without
      complications, and group G --consisting of 12 pregnant women, 4 with gestational
      diabetes mellitus and 8 with pregestational diabetes mellitus, who developed
      preeclampsia, in course of research, after 37th week of pregnancy. Concentration
      of FN and Fm--in order to the state of carbohydrate metabolism--was marked in the
      following: before 33rd week of pregnancy, between 33rd and 37th week of pregnancy
      and after 37th week of pregnancy. RESULTS: No correlation between concentration
      of FN and duration of pregnancy in group K was found. Average concentration of FN
      in the subsequent periods of the pregnancy in group K were similar and have not
      shown vital, statistical differences. In group G crucial statistical increase in
      FN concentration along with increase of pregnancy duration was found (r = 0.3860,
      p < 0.07). No correlation between concentration of FN nor Fm was found in both
      groups. CONCLUSIONS: The results obtained demonstrate that vascular endothelial
      damage, as expressed by increase in plasma fibronectin levels, is a condition
      specific for preeclampsia, preceding its clinical manifestation. Maternal blood
      concentrations of FN do not depend on the state of carbohydrate metabolism
      estimated by concentration of Fm.

PMID- 18819454
TI  - [Probability rates for different pregnancy outcomes in carriers of reciprocal
      chromosomal translocations involving chromosome 13].
AB  - OBJECTIVES: The aim of study was to estimate the probability rates for
      unfavorable pregnancy outcomes in carriers of reciprocal chromosomal
      translocations involving 13 chromosome (RCT-13q). MATERIAL AND METHODS: We
      collected total empirical data about 232 pregnancies of 56 carriers coming from
      28 pedigrees. RCT classification was based on classic cytogenetic methods for
      interpretation of breakpoint position. The probability rates of particular type
      of pathology related to the total number of pregnancies after ascertainment
      correction have been calculated with the help of Stengel-Rutkowski and Stene
      method. RESULTS: The risk figures for unbalanced offspring after 2:2 disjunction
      and adjacent-1 segregation for the whole group of pedigrees were calculated as
      5.2 +/- 1.7% (9/173)--medium risk, for maternal (MAT) and paternal (PAT) carriers
      were about 6.2 +/- 2.3% (7/173) and 4.8 +/- 3.3% (2/42) respectively. Considering
      different segment lengths of 13q, similar values for shorter and longer segments
      were obtained [4.3 +/- 1.9% (5/115) for 13q21-->qter and 7.0 +/- 3.3% (4/58) for
      13q12-->qter]. The risk figures for miscarriages as 36.4 +/-3.6% (63/173) and for
      stillbirths/early death as 4.6 +/- 31.6% (8/173) were obtained. The risk figures
      for unbalanced offspring after 3:1 disjunction were calculated as 7.7 +/- 7.45
      (9/13). CONCLUSIONS: 1. Risk figures for different pregnancy outcomes are differ
      among particular forms of pathology. 2. Probability rate for unbalanced progeny
      at birth was calculated as a medium risk and similar values for carriers of
      different segments of 13q were obtained. 3. Probability rate for miscarriages was
      high but risk for stillbirths/early deaths of newborn was low. 4. No differences
      in values of rate for particular forms of pathology were found for maternal and
      paternal carriers of RCT-13q.

PMID- 18819455
TI  - [Operative treatment of benign ovarian tumours in adolescent patients: laparotomy
      or laparoscopy?].
AB  - THE AIM: The aim of the study was a retrospective analysis of operative
      procedures, laparoscopy or laparotomy, carried out in cases of benign adolescent
      ovarian tumours. MATERIAL AND METHODS: A retrospective review of 709 patient
      charts with ovarian tumours, who had undergone surgical interventions at The
      Department of Surgical Gynaecology and Endoscopy of The Polish Mother's Memorial
      Hospital--Research Institute in Lodz--has been conducted. Among groups of girls
      treated either with laparoscopy or laparotomy, the following parameters were
      analysed: age of the patients, character of the tumour (based on the pathological
      result), size of the lesion, type of the surgical procedure, duration of the
      hospitalisation and postoperative complications. RESULTS: 109 girls had ovarian
      tumours operated--54 times laparoscopy and 55 laparotomy times were performed. An
      average age of patients who underwent laparoscopy was 16.2 years, in case of
      laparotomy: 15.3 years (p > 0.05). An average size of tumours excised in
      laparotomy was 82 mm (60-190 mm), whereas in laparoscopy 64 mm (30-80 mm) (p >
      0.05). The most common laparotomic procedure was the ovarian cystectomy (63%) and
      cystovariectomy (32%), while during laparoscopy the cystectomy was performed in
      92% (p > 0.05). Duration of the laparoscopy was shorter, average was 46.7 min,
      whereas mean time of laparotomy was 49.2 min (p > 0.05). Also duration of
      postoperative hospitalisation was longer in case of laparotomy, its average time
      was 5.4 days in comparison with laparoscopy--2.8 days (p < 0.05). CONCLUSIONS:
      Laparoscopy performed in adolescents due to benign ovarian tumours seems to be a
      very safe way of the surgical treatment. Moreover, laparoscopy reduces duration
      of hospitalisation and convalescence, also giving a nice cosmetic effect.

PMID- 18819456
TI  - [The correlation of a positive DNA HPV HR test and genotyping human papilloma
      viruses with the presence of CIN, in women with cytologic evidence of ASC-US and
      LSIL].
AB  - INTRODUCTION: Diagnostic algorithm for women with ASC-US presumes the possibility
      of performing molecular test for DNA HPV HR, colposcopy or repeated cytology. The
      latest suggestions of diagnostic algorithm modification in case of cytologic
      interpretation of LSIL, are based on trial of performing molecular DNA HPV HR
      test and/or genotyping human papilloma viruses with the special indication for
      type 16. These suggestions presume performing colposcopy in women with DNA HPV HR
      or DNA HPV 16 (+). MATERIAL AND METHOD: Triage study included 67 women with ASC
      US and 48 women with LSIL. All 115 women were examined with the use of molecular
      test Amplicor HPV Roche Diagnostics, which identifies the presence of any out of
      13 oncogenic DNA HPV types. 14 women with LSIL DNA HPV HR (+) interpretation,
      were additionally tested for identification of HPV genotypes presence. In all
      women with cytologic evidence of ASC-US and LSIL, a colposcopic examination was
      further performed. RESULTS: Among 67 examined women with ASC-US interpretation,
      31 had a (+) test for the presence of any out of 13 HPV HR, while in 12 patients,
      the result of pathomorphological examination confirmed at least the presence of
      CIN 1. In none of 36 patients with ASC-US, DNA HPV HR (-) interpretation, the
      presence of CIN was confirmed. For 29 women with LSIL, (+) test result for any
      out of 13 HPV HR was obtained. In 117 patients OUT of this group, at least the
      presence of CIN 1 was recognized. Following 19 women with LSIL had a negative
      test result for DNA HPV HR. In none of the patients with DNA HPV HR (-), the
      presence of CIN was confirmed. DNA HPV 16 was recognized in 5/9 patients with
      LSIL, without CIN. In 5 patients with LSIL, who underwent HPV genotyping, and
      were diagnosed for CIN, 4/5 were DNA HPV 76 (+). The most common HPV types in
      women with LSIL and the presence of CIN include; HPV 16 and HPV 37. CONCLUSIONS:
      1. Negative DNA HPV HR result, identifies precisely women with ASC-US and LSIL,
      without CIN. 2. Genotyping exclusively DNA HPV 16 in women with LSIL, in order to
      detect CIN is characterized by lower sensitivity and specificity in comparison
      with universal test for 13 oncogenic HPV types.

PMID- 18819457
TI  - [Evaluation of Cicatridine efficacy in healing and repairing process of uterine
      cervix, vagina and vulva--open no-randomized clinical study].
AB  - PURPOSE: The aim of the study was to evaluate the efficacy of Cicatridine
      application in healing and repairing process after operative procedures
      concerning uterine cervix, vagina and vulva and after brachytherapy due to
      cervical and endometrial cancer. We also analyzed Cicatridine effect on vaginal
      athrophical signs in post-menopausal women. PATIENTS AND METHODS: The examined
      group consist of 319 women. They were divided into 2 arms. The active arm
      concerns 213 women who used Cicatridine, while controlled one consists of 106
      women. The effect of treatment was estimated after 6 weeks and 3 months by the
      visual inspection of the cervix and vagina. We also analyzed the subjective
      filling of patients bound to sexual intercourses by using of Visual Analogue
      Scale (0%--no effect; 100%--disappearance of pathological symptoms). RESULTS: In
      active arm according to control one the reparation of cervix was more often:
      after surgery procedures (respectively after 6 weeks 93% vs 70%; after 3 months
      99% vs 89%) and after brachytherapy (respectively after 3 months 86% vs 0%). In
      brachytherapy group the lack of discomfort during sexual intercourses was also
      more often in active arm (respectively 55% vs 0%). In postmenopausal women
      reduction of symptoms associated with atrophic vaginitis was observed only in
      active group (respectively after 6 weeks 43% vs 0%; after 3 months 57% vs 0%). In
      the group of patients after ephisiotomy due to delivery the relief of discomfort
      during sexual intercourses was also more often in active arm respectively 94% vs
      25%). CONCLUSION: Cicatridine causes fast healing of cervix after gynecological
      procedures. It influences improvement of atrophical, inflammatory and after
      radiation therapy effects which improve quality of life and comfort of vagina
      after brachytherapy due to cervical and endometrial cancer. Cicatridine causes
      similar effect in vagina of post-menopausal women as locally used estrogens.
      Cicatridine also causes the feeling of relief and comfort in vagina after
      delivery as well as fast healing after episiotomy.

PMID- 18819458
TI  - [Dysmenorrhea in pediatric and adolescent gynaecology].
AB  - Dysmenorrhea is the most common problem in pediatric and adolescent gynaecology
      and it reaches approximately 20-90% of adolescents and young adult females.
      Dysmenorrhea in adolescent girls is usually primary and is associated with normal
      ovulatory cycles and with no pelvic pathology. Secondary dysmenorrhea, associated
      with some pelvic pathology, constitutes approximately 10% of the cases and its
      most frequent reasons are: endometriosis, pelvic inflammatory disease, congenital
      mullerian anomalies and ovarian cysts. Prostaglandins and leukotriens play a
      significant role in etiopathogenesis of the primary dysmenorrhea. The therapy of
      the primary dysmenorrheal in adolescent girls involves: nonsteroidal anti
      inflammatory drugs for at least 3 months, combined with oral contraceptives for
      at least 3-6 menstrual cycles, as well as dietary supplementation, other
      alternative therapies (vitamins, herbal remedies, acupuncture, TENS) and surgical
      treatment Secondary causes of dysmenorrhea should be considered in adolescents
      with dysmenorrhea who do not respond to the treatment. The role of the pediatric
      and adolescent gynaecologist is to diagnose the reason of symptoms, educate the
      patient, review effective treatment options as well as to restore normal daily
      functioning.

PMID- 18819459
TI  - [Intraperitoneal chronic exudation as a complication after giant ovarian cyst
      removal in a 76-year-old woman. A case report].
AB  - The article offers a description of a clinical course of treatment of a 76-year
      old woman who had undergone a giant ovarian cyst removal. After the surgery, a
      chronic intraperitoneal exudation occurred in the quantity of over one liter per
      day for twenty two days after the intervention. The chronic exudation caused
      significant electrolyte disturbance and protein deficiency. It was confirmed that
      in the event of proper electrolytes and proteins supplementation, the phenomenon
      of the massive exudation does not present a direct threat to the patient,
      although the course of the treatment lengthens significantly.

PMID- 18819460
TI  - [Thrombotic thrombocytopenic purpura in pregnancy. A case report].
AB  - Thrombotic thrombocytopenic purpura (TTP) is characterized by microangiopathic
      hemolytic anemia and thrombocytopenia, accompanied by microvascular thrombosis
      that causes variable degrees of tissue ischemia and infarction. About 10-20% of
      TTP cases are associated with the pregnancy. Preterm delivery and intrauterine
      fetal death are frequent pregnancy complications of TTP. The following paper
      presents the case of a 32-year-old woman with TTP relapse at 10 weeks of her
      second pregnancy. Despite regular fresh frozen plasma transfusions, intrauterine
      fetal death occurred at 21 weeks of gestation. Current views on TTP management
      during pregnancy have been presented in the article as well.

PMID- 18819461
TI  - [Hospital-acquired infections after caesarean delivery in selected hospitals in
      the southern Poland].
AB  - OBJECTIVE: The aim of this study was the epidemiological and microbiological
      analysis of hospital acquired infections (HAIs) among patients after caesarean
      section (CS) procedures in two hospitals in southern Poland between 2004 and
      2006. MATERIALS AND METHODS: 1992 CS procedures were performed in both hospitals
      during the investigated period of time and 91 cases of HAI were detected. In each
      case, the etiology of HAI was assessed. Definitions and criteria of HAIs were
      based on those of NNIS program of CDC. RESULTS: General morbidity rates were 4.1%
      (hospital no. 1) and 4.8% (hospital no. 2) and surgical site infections (SSIs)
      rates were 3.9% and 3.8%, respectively. The difference between those rates and
      the rates published by NNIS hospitals was not statistically important Most of the
      detected cases of SSIs were detected during patients' stay at the hospitals.
      Dominant etiological factors of the SSIs were Gram positive cocci(hospital no. 1)
      and Gram negative bacilli (hospital no. 2). CONCLUSIONS: Results obtained in the
      study confirm the possibility of introducing HAIs control programs in Polish
      obstetric wards and also the necessity of HAIs detection after discharging
      patients from the hospital. Unfortunately, lack of data from other Polish
      hospitals makes it impossible to assess the situation in the country.

PMID- 18819462
TI  - The 3020insC NOD2 gene mutation in patients with ovarian cancer.
AB  - OBJECTIVE: There is an increasing evidence that genetic factors play a role in
      the etiology of malignant tumors. Mutations of BRCA1 and BRCA2 genes are
      responsible for an increased risk of ovarian cancer. The role of mutations in
      NOD2 gene in this type of neoplasm is still under investigation. THE AIM: The aim
      of this study was to determine: 1. incidence of NOD 2 3020insC constitutional
      mutation in a group of consecutive women with ovarian cancer, 2. risk of
      developing ovarian cancer in patients with NOD2 gene mutation, 3. clinical and
      pathological features of ovarian cancer in NOD2 gene mutation carriers. PATIENTS
      AND METHODS: Clinical and pathological data were collected from 257 non-selected
      patients with primary epithelial ovarian cancer. The researches identified NOD2
      3020insC gene mutation. On the basis of patient source documentation we obtained
      the data concerning the age of patients at diagnosis, histopathological
      recognition, FIGO stage and morphological grade G. RESULTS: 19 out of 257 women
      were identified with germ-line 3020insC mutation of NOD2 gene (7.39%). An
      increased risk of ovarian cancer in NOD2 mutation carriers was not revealed
      (OR=1.01; p=0.928; 95% Cl=0.61-1.66). The mean age at diagnosis of patients with
      NOD2 mutation was 54.8 (SD=9.9), while for non-carriers it was 53.2 (SD=10.2).
      The difference between these frequencies was statistically irrelevant (p=0.550).
      Clinical and pathological profile of ovarian cancer was made. We assessed the
      following features: age at disease onset, histopathology, FIGO stage and
      morphological grade G. For NOD2 mutation carriers no statistically significant
      features of ovarian cancer were revealed. CONCLUSION: 1. Despite high frequency
      of constitutional mutations occurrence in NOD2 gene in women with ovarian cancer,
      genetic testing seem not to be justified in all women diagnosed with this
      disease. 2. Due to a lack of increased risk of ovarian cancer in NOD2 gene
      mutation carriers, proceedings for them may not differ from recommendations for
      general population. 3. It is difficult to determine characteristic clinical and
      pathological features of ovarian cancer for NOD2 gene mutation carriers.

PMID- 18819463
TI  - [Management of selected complications following urogynecological surgeries with
      the use of synthetic prostheses--own observations].
AB  - The article presents the results of treatment and management of certain selected
      complications following urogynecological operations with the use of synthetic
      materials. The study group consisted of 76 women with vaginal wound healing
      problem after surgical treatment of POP with the use of polypropylene
      monofilament mesh: vaginal erosion (44), protrusion of the mesh (18), vaginal
      granulation (14) - after surgical treatment of Pelvic Organ Prolapse (POP) with
      the use of polypropylene monofilament mesh. The article describes the applied
      methods of treatment of the above mentioned complications, as well as their
      effectiveness. The conservative way of treatment was found to be the best way of
      treating vaginal granulation, partial removal of the synthetic material proved to
      be the best method of treating vaginal erosion, whereas in case of mesh
      protrusion - total polypropylene prosthesis removal was necessary.

PMID- 18819464
TI  - [Fibroblast growth factor gene expression in uterine leiomyomas].
AB  - OBJECTIVES: The aim of the study was the evaluation of acidic and basic FGF
      expression, as well as collagenolitic activity in human uterine leiomyomas at
      various stages of tumour growth. MATERIAL AND METHODS: Studies were performed on
      human myometrium and uterine leiomyomas of various weights (small: i.e. less than
      10 g, and large: i.e. more than 100 g). The RT-PCR method was used to determine
      the acidic and basic FGF mRNA levels. The content of both FGF was evaluated by
      immunoenzymatic method (ELISA). The collagenolitic activity was detected by
      zymography. RESULTS: A distinct increase in the expression of aFGF, the amounts
      of both FGFs, and collagenolitic activity was observed during the tumour growth.
      CONCLUSIONS: Myometrium conversion into leiomyoma and an increase in its mass is
      accompanied by a significant increase in aFGF gene expression. The collagenolitic
      activity elevation favours a release of both FGF isoform from complexes with
      extracellular matrix components.

PMID- 18819465
TI  - [Introduction of the Birthcenter System (according to Belegsystem) in Germany-
      comments].
AB  - Recent years have undoubtedly been a time of dynamic changes for German midwives,
      which had had their source in numerous social, economic and political changes.
      The medical care cost growth, lack of profitability of medical centers and an
      increasing number of redundancies have been given lots of attention in various
      discussions. The above mentioned problems have started to concern the
      professional group of German midwives, thus giving birth to the introduction of
      innovatory system of obstetric care in German hospitals, known as Belegsystem. In
      Europe the Belegsystem has been introduced in certain Scandinavian countries,
      Great Britain, Austria and Switzerland. In Germany the first labour room within
      the Belegsystem rules has been opened on 1 June 2003 in Brema (Klinikum
      Bremerhaven Reinkenheide). The following two Centers have been opened in Hamburg
      at the beginning of 2004 (Allgemeines Krankenhaus Hamburg-Harburg i Allgemeines
      Krankenhaus Hamburg-Barmbek). The folllowing article presents the functioning
      rules and procedures of the Belegsystem labour rooms in Germany, as one of the
      labour care alternatives.

PMID- 18819466
TI  - [Krukenberg tumor--8 years after surgical treatment of gastric carcinoma].
AB  - The aim of the study was to discuss the case of Krukenberg tumor in a patient,
      eight years after the diagnosis and surgical treatment of gastric carcinoma. We
      have concluded that there was no safe period after which distant metastases may
      be excluded. In case of gastric carcinoma diagnosed in women, a regular
      gynecological examination is necessary due to a high propability of metastases
      into ovaries, even if the clinical stage of gastric carcinoma is low.

PMID- 18819467
TI  - [Polish Gynecological Society's recommendations regarding prevention of labor
      pain Part II: Treatment of pain during pregnancy, labor, and postpartum period].

PMID- 18819468
TI  - [Progress in small-molecule inhibitors of Bcl-2 family proteins].
AB  - Apoptosis is an essential factor in keeping homeostasis of the organism.
      Apoptosis is regulated by a series of cytokines. Bcl-2 family proteins are key
      regulators of apoptosis. The Bcl-2 family includes both anti- and pro-apoptotic
      proteins with opposing biological functions. Their interaction regulates the
      transmission of the apoptosis signal. High expression of anti-apoptotic members
      such as Bcl-2 and Bcl-xL are commonly found in human cancers. In recent years,
      following the disclosing of the crystal structures of Bcl-2 family proteins,
      researchers have paid attention to the development of the small molecule
      inhibitors of Bcl-2 family proteins. This article reviews the progress in this
      field from the view of drug design.

PMID- 18819469
TI  - [Advances in the study of molecular mechanism of APOBEC3G anti-HIV-1].
AB  - Apolipoprotein B mRNA-editing enzyme catalytic polypeptide 3 protein G (APOBEC3G)
      is part of the innate immune system of host cells and has cytidine deaminase
      activity. It specifically incorporates into the virion during HIV-1 replication.
      The incorporation of APOBEC3G needs its interaction with HIV-1 Gag. In the HIV-1
      reverse transcription process, APOBEC3G deaminates dC to dU in the first minus
      strand cDNA, and then induces extensive hypermutation in the viral genome.
      Besides deamination, APOBEC3G also inhibits HIV-1 by some kinds of non
      deamination mechanisms which need to be further elucidated. HIV-1 Vif counteracts
      the activity of APOBEC3G by an ubiquitin-proteasome-mediated degradation of
      APOBEC3G. As a broad spectrum inhibitor of viruses, APOBEC3G also inhibits
      various retroviruses, retrotransposons and other viruses like HBV. Upregulating
      the expression of APOBEC3G or blocking the Vif-mediated degradation of APOBEC3G
      might be novel strategies to treat HIV-1 infection in the future.

PMID- 18819470
TI  - [Integration of metabonomics technology and its application in modernization of
      traditional Chinese medicine].
AB  - Metabonomics technology has been widely applied in the field of biology and
      pharmacy nowadays. The integration on mass spectrometry, nuclear magnetic
      resonance, and other modern analytical techniques, made up of the metabonomics
      technology platform, have accelerated the study on metabonomics. In this paper,
      the past results of metabonomics studies are reviewed, and the applications of
      metabonomics to traditional Chinese medicine are prospected.

PMID- 18819471
TI  - [Exendin-4 protected murine MIN6 pancreatic beta-cells from oxidative stress
      induced apoptosis via down-regulation of NF-kappaB-iNOS-NO pathway].
AB  - To explore the effect of glucagon-like peptide-1 receptor agonist--Exendin-4 (Ex
      4) on murine MIN6 pancreatic beta-cells apoptosis induced by oxidative stress,
      the morphological changes of cell damage were evaluated by epifluorescence
      microscopy after staining with AO-EB. The percentage of cell apoptosis was
      determined by flow cytometric assay after Annexin-V-FITC-PI staining. Nitric
      oxide level was measured by Griess reagent assay. Inducible nitric oxide synthase
      (iNOS) protein and NF-kappaBp65 fragment were detected by Western blotting. Ex-4
      inhibited the increase of nitrite level and percentage of apoptosis induced by t
      BHP in MIN6 cells. Furthermore, Ex-4 partly reduced the expression of iNOS
      protein and the ratio of NF-kappaBp65 protein in nucleus:cytosol induced by t
      BHP. These results suggest that Ex4 protects MIN6 pancreatic kappa-cells from
      oxidative stress-induced apoptosis via down-regulation of NF-kappaB-iNOS-nitric
      oxide pathway.

PMID- 18819472
TI  - [Population pharmacokinetics of tacrolimus in Chinese renal transplant patients].
AB  - The goal of this study is to investigate the population pharmacokinetics of oral
      tacrolimus in Chinese renal transplant patients and to identify possible
      relationship between covariates and population parameters. Details of drug dosage
      history, sampling time and concentration of 802 data points in 58 patients were
      collected retrospectively. Before analysis, the 58 patients were randomly
      allocated to either the model building group (n=41) or the validation group
      (n=17). Population pharmacokinetic data analysis was performed using the
      nonlinear mixed-effects model (NONMEM) program on the model building group. The
      pharmacokinetics of tacrolimus was best described by a one compartment model with
      first-order absorption and elimination. Typical values of apparent clearance
      (CL/F), apparent volume of distribution (V/F) were estimated. A number of
      covariates including demographic index, clinical index and coadministration of
      other drugs were evaluated statistically for their influence on these parameters.
      The final population model related clearance with POD (post operative days), HCT
      (haematocrit), AST (aspartate aminotransferase) and coadministration of
      nicardipine and diltiazem. Predictive performance of the final model evaluated
      with the validation group showed insignificant bias between observed and model
      predicted concentrations. Typical value of CL/F and V/F was 21.7 L x h(-1) and
      241 L, inter-patient variability (RSD) in CL/F and V/F was 41.6% and 49.7%,
      respectively. The residual variability (SD) between observed and model-predicted
      concentrations was 2.19 microg x L(-1). The population pharmacokinetic model of
      tacrolimus in Chinese renal transplant patients was established and significant
      covariates on the tacrolimus model were identified.

PMID- 18819473
TI  - [Anti-HIV activities of Achyranthes bidentata polysaccharide sulfate in vitro and
      in vivo].
AB  - Achyranthes bidentata polysaccharide sulfate (ABPS) was a sulfated derivate
      derived from Achyranthes bidentata polysaccharide (ABP) which was isolated and
      identified from Chinese herb Achyranthes bidentata. The anti human
      immunodeficiency virus type 1 (HIV-1) activities were studied in vitro and in
      vivo. ABPS was found to inhibit HIV-1 reverse transcriptase and integrase with
      the 50% inhibiting concentration (IC60) of (2.948 +/- 0.556) micromol x L(-1) and
      (0.155 +/- 0.030) micromol x L(-1), respectively, but the parent compound ABP was
      not effective. ABPS inhibited HIV-1 P24 antigen with IC50 of (0.082 +/- 0.044)
      micromol x L(-1) and selective index (SI) of > (358 +/- 148) in MT-4 cell
      cultures acutely infected with HIV-1 IIIB virus, and with IC50 of (11.80 +/-
      5.90) micromol x L(-1) and SI of > (24.2 +/- 12.1) in PBMC cell cultures acutely
      infected with clinical isolated zidovudine resistant HIV-1 virus, but there was
      no activity even at its concentration of 500 micromol x L(-1) in latent infection
      of H9/HIV-1 IIIB cell cultures. 5% sera taken from rats after intraperitoneal
      injection from rats with ABPS 125 mg x kg(-1) once or mice with 3 mg x kg(-1) qd
      for 20 days effectively inhibited HIV-1 P24 in MT-4 cell cultures, but those had
      no inhibitory effect when given orally. The results suggested that ABPS is a
      promising HIV-1 inhibitor, active on HIV-1 reverse transcriptase, integrase in
      vitro and HIV-1 P24 antigens in cell cultures, it was well absorbed by
      intraperitoneal injection but poor in oral bioavailability. It warrants further
      study.

PMID- 18819474
TI  - Improved synthesis and pharmacological evaluation of racemic 11 
      demethylcalanolide A.
AB  - An improved and practical synthesis of racemic 11-demethylcalanolide A [(+/-)-1]
      was developed. This improved process involved Pechmann reaction on phloroglucinol
      with ethyl butyrylacetate to give 5,7,-dihydroxy4-n-propylcoumarin (3). Poly
      phosphoric acid (PPA) catalyzed acylation of compound (3) with crotonic acid,
      then intramolecular cyclization was achieved simultaneously in one step to afford
      the key intermediate chromanone (4). A microwave assisted synthetic method
      preparing chromene (6) using chromenynation of chromanone (4) with 1, 1-diethoxy
      methyl-2-butene was conducted. Luche reduction of chromene (6) using NaBH4 with
      CeCl3 x 7H2O preferably gave (+/-)-1. The overall yield of this four step
      synthesis of (+/-)-1 was around 32% increasing one fold more than that of the
      previous method. An in vitro investigation showed that (+/-)-1 exhibited
      inhibitory activities against both wild-type and drug-resistant HIV-1 in HIV-1 RT
      and cell culture assay, and significant synergistic effects in combination with
      AZT, T-20, and indinavir. Its LD50 of acute toxicity in mice by intragastric
      administration and by intraperitoneal injection were 735.65 mg kg(-1) and 525.10
      mg x kg(-1), respectively. The Cmax and AUC(0-infinity) were 0.54 microg x mL(-1)
      and 1.08 (microg x mL(-1) x h, respectively. The dynamics study of the inhibition
      of mice sera on HIV-1 RT showed that mice treated with 100 mg x kg(-1 (+/-)-1
      once intraperitoneally were similar to that of 5 mg x kg(-1) of known clinical
      effective anti-HIV-1 drug neverapine. The results suggested that further
      investigation of the anti-HIV candidate (+/-)-1 was warranted.

PMID- 18819475
TI  - [Synthesis and in vitro antioxidant activity of homo- and heterocyclic diene
      derivatives of glycyrrhetol].
AB  - Chemical modification was performed for improving the antioxidant activity of
      lead compound glycyrrhetinic acid (Ib). Two conjugated diene derivatives were
      prepared by reduction and dehydration reactions. Their in vitro antioxidant
      activities were studied using a cytochrome P450/NADPH reductase system from rat
      liver microsomes. The generation of microsomal free radicals was followed by
      oxidation of the DCFH-DA probe, while evaluating the capacity to inhibit reactive
      oxygen species (ROS) formation. The initial result showed that the two homo- and
      heterocyclic diene derivatives--18beta-olean-11,13(18)-diene-3beta, 30-diol (IV)
      and 18beta-olean-9 (11), 12-diene-3beta, 30-diol (V) exhibited strong antioxidant
      activities, at a concentration of 1.0 mg x mL(-1), they inhibited free radical
      (ROS) formation by 45% and 41%, respectively. In the same conditions, the lead
      compound (Ib) and the reference vitamin E inhibited ROS activity by 31% and 32%.
      Our results suggest that the elimination of the 11-keto group and the chemical
      reduction of 30-carboxylic group into hydroxyl function can increase the
      antioxidant activity of Ib significantly.

PMID- 18819476
TI  - Alkaloid and sesquiterpenes from the root tuber of Curcuma longa.
AB  - One new quinoline alkaloid and seven known bisabolane sesquiterpenes: 2-(2'
      methyl-1'-propenyl)-4, 6-dimethyl-7-hydroxyquinoline (1), 2, 5-dihydroxybisabola
      3, 10-diene (2), 4, 5-dihydroxybisabola-2,10-diene (3), turmeronol A (4),
      bisacurone (5), bisacurone A (6), bisacurone B (7) , bisacurone C (8), as well as
      dehydrozingerone (9) and zingerone (10) were isolated from the root tuber of
      Curcuma longa. Their structures were identified by spectral evidence. Compound 1
      is a new compound, compounds 6 -8 were isolated from this plant for the first
      time and compounds 9 - 10 from Curcuma for the first time.

PMID- 18819477
TI  - [HPLC fingerprint of the components of Radix Angelicae Sinensis].
AB  - A chemical fingerprint method was developed for investigating the variance of
      constituents between the whole roots and prepared slices of Radix Angelicae
      Sinensis (the roots of Angelica sinensis) using HPLC. 19 Radix Angelicae Sinensis
      whole roots collected from 16 different habitats and 28 commerial drugs including
      6 whole roots, 1 root head and 21 prepared slices were analyzed. The component
      fingerprint of Radix Angelicae Sinensis with 12 common peaks was established.
      Common peaks 2, 5 and 6 could not be detected in most of the prepared slice
      samples. Except peaks 11 and 12, all the other peaks in graphics of the prepared
      slice samples mostly showed lower responses than those of the whole root samples.
      The whole roots and prepared slices could also be divided into two groups based
      on the clustering analysis results done by SAS 8.2. Meanwhile, the Similarity
      Evaluation System for Chromatographic Fingerprint of TCM 2004 software was
      applied for data analysis. Except samples y-17, s-3, s-5 and s-6, the
      similarities of the whole root samples were over 0.973, while the similarities of
      the prepared slice samples were all below 0.969. All the results demonstrated
      that there was distinguished difference in chemical components between the whole
      roots and prepared slices of Radix Angelicae Sinensis. Our experiments suggested
      to maintain the active components, whole roots of Radix Angelicae Sinensis should
      be a better choice than prepared slices for medicine trade and the storage of
      Radix Angelicae Sinensis should be taken care of.

PMID- 18819478
TI  - [Determination of tiopronin in rat plasma by HPLC following fluorescent
      derivatization].
AB  - A sensitive, rapid method for determining reduced tiopronin concentration in rat
      plasma has been developed by using a high-performance liquid chromatography
      (HPLC) technique in conjunction with the derivatizing agent N-(1-pyrenyl)
      maleimide (NPM). The analytes were separated on a Kromasil C18 column (250 mm x
      4.6 mm, 5 microm) using 0.2% glacial acetic acid aqueous solution including 0.015
      mol x L(-1) KH2PO4 and acetonitrile (56:44) as a mobile phase at a flow-rate of
      0.8 mL x min(-1), and fluorescence detection wavelength were set at lamda(e x) =
      340 nm and lamda(e m) = 375 nm, the column temperature was 30 degrees C. The
      calibration curve was found to be linear over a range of 0.1 - 10.0 microg x mL(
      1), the limit of quantitation was 0. 1 mg x L(-1). The coefficients of the
      variation for the within-run and between-run precisions ranged from 5.3% to 10.8%
      and 7.0% to 10.8%, respectively. The percentage of absolute recovery ranged from
      73.7% to 79.7%. The method was used to determine the concentration of tiopronin
      in rat plasma after a single intragastric administration of 25 mg x kg(-1)
      tiopronin to 6 healthy male Wistar rats. The pharmacokinetic process was fitted
      to a two-compartment model. The method has been successfully applied to the
      determination of tiopronin in rat plasma.

PMID- 18819479
TI  - [Primary structure determination of hirudin and reteplase fusion protein by
      LC/ESI-MS/MS spectrometry].
AB  - The aim is to determine the primary structure of a new hirudin and reteplase
      fusion protein (HV12p-rPA) by LC-ESI-MS/MS spectrometry. The molecular weight of
      the hirudin and reteplase fusion protein (HV12p-rPA) was measured by matrix
      assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF
      MS). The HV12p-rPA was digested with trypsin and chymotrypsin separately and the
      peptides in the digest mixtures were identified by LC-ESI-MS/MS. The molecular
      weight of HV12p-rPA was 41,472 Da, which was in accordance with the theoretical
      value. The peptide fragments of HV12p-rPA digested with trypsin were identified
      by LC-ESI-MS/MS spectrometry and the results indicated that the fusion protein
      contained r-PA. Then, the peptides of HV12p-rPA digested with chymotrypsin were
      identified by the same method. The results indicated that the fusion protein
      contained HV12p and the linker-containing peptide, DEGGGSY. MASDF and LDWIRDNMRP
      were identified as the N-terminal and C-terminal containing peptides in the
      chymotryptic digest mixture of the fusion protein. All of the Xcorr values
      exceeded 1.5, some of which were above 3.0, showing that the results were correct
      and credible and a sequence coverage of 85% was achieved. HPLC/MS analysis
      coupled with uncompleted digestion indicated that all these peptides were
      arranged with the correct order as expected. Thus, sequence of the fusion protein
      was confirmed and it was consistent with our design in upstream construction.

PMID- 18819480
TI  - [Preparation of doxorubicin-loaded chitosan polymeric micelle and study on its
      tissue biodistribution in mice].
AB  - To prepare doxorubicin-loaded N-octyl-N'-succinyl chitosan polymeric micelle (DOX
      OSC) and study the biodistribution of DOX-OSC in mice, DOX-OSC was prepared by
      dialysis method. By using doxorubicin injection (DOX-INJ) as control, DOX-OSC and
      DOX-INJ were administered to mice through caudal vein at a dose of 5 mg x kg(-1)
      body weight. The RP-HPLC method was established to determine the DOX levels in
      the plasma and other tissues of mice. The tissues distribution and targeting
      efficiency were evaluated by pharmacokinetic parameters (AUC, MRT) and targeting
      parameters (Re, Ce and Te). The drug loading and entrapment efficiency of DOX-OSC
      were (35.8 +/- 0.4)% and (75.3 +/- 1.1)%, respectively. The diameter and zeta
      potential of DOX-OSC were (174 +/- 12) nm and (-37.1 +/- 3.0) mV, respectively.
      The transmission electron microscope result showed DOX-OSC with spherical shape.
      The biodistribution results showed that the concentration of DOX of both DOX-OSC
      and DOX-INJ decreased rapidly in blood after iv administration. While free DOX
      levels in blood at 12-96 h were not detectable for DOX-INJ, in contrast, DOX
      level in blood at 96 h was still found for DOX-OSC. In contrast to DOX-INJ group,
      DOX-OSC showed a higher targeting efficiency in the liver and spleen. The AUCs of
      DOX in the liver and spleen were 20.0 and 47.4 times and the MRT were 11.2 and
      37.2 times, respectively. And the levels of DOX-OSC in the heart and kidney
      tissues were significantly reduced. And the drug distribution of DOX-OSC in the
      heart and kidney tissues were 17.0% and 11.4%, respectively. Hence, DOX-OSC shows
      an excellent drug loading capabilities and a higher targeting efficiency in the
      liver and spleen. That the levels of DOX-OSC in the heart and kidney tissues are
      significantly reduced, might improve the treatment efficacy of DOX and decrease
      the side effects.

PMID- 18819481
TI  - [Preparation and in vitro corneal retention behavior of novel cationic
      microemulsion/in situ gel system].
AB  - The aim was to prepare a novel ocular cationic microemulsion-in situ gel (CM-ISG)
      system with vitamin A palmitate (VAP) as model drug, and investigate the corneal
      retention behavior and corneal irritation of the system. VAP/CM was prepared by a
      process based on supply of energy, and the before-and-after gelation rheology of
      VAP/CM-ISG was investigated. In vitro VAP release and gel dissolution of both
      VAP/CM-ISG and Oculotect Gel was determined. And in vitro corneal retention
      behavior of both formulations was evaluated by captive bubble technique. Ocular
      irritation test was carried out based on the Draize method. Images of TEM showed
      that homogenous VAP/CM was made, and no significant differences of particle size
      were found between the VAP/CM and VAP/CM in Poloxamer 407 gel. Rheology study
      illustrated that VAP/CM reduced the phase transition temperature of Poloxamer 407
      gel by 1.5 degrees C, and the elastic modulus increased about 15.7 times. The in
      vitro release and gel dissolution profile of both formulations exhibited the
      characteristics of zero order kinetics. Comparing with Oculotect Gel, desorption
      kinetics study of VAP/CM-ISG exhibited longer corneal retention time and smaller
      contact angle. Irritation test showed a good ocular compatibility of VAP/CM-ISG.
      Therefore, VAP/CM-ISG combined both advantages of the cationic microemulsion and
      in situ gel system, provided better wettability and longer ocular retention time.
      It might be a promising ocular drug delivery system.

PMID- 18819482
TI  - [Preparation of sustained release multivesicular liposome for thymopentin and
      preliminary study on its pharmacokinetics in rats].
AB  - To optimize the formulation and preparation method of multivesicular liposome of
      thymopentin and to investigate its pharmacokinetics in rats, the multivesicular
      liposome of thymopentin was prepared by double emulsification method and the
      formulation was optimized by orthogonal design. The release characteristics of
      thymopentin from multivesicular liposome in PBS (pH 7.4) and in plasma were
      investigated. The multivesicular liposome of thymopentin labeled with fluorescein
      isothiocyanate was prepared by double emulsification method. Its pharmacokinetics
      was evaluated following intramuscular injection in rats. The optimal formulation
      of multivesicular liposome of thymopentin were formulated with 7.5% glucose in
      aqueous phase and 2.25 mol x L(-1) triolein, 2.68 mol x L(-1) DPPG and 16.96 mol
      x L(-1) DOPC in organic phase. The entrapment efficiency of the multivesicular
      liposome of thymopentin was above 85% and the mean particle size was about 22
      microm. The in vitro release of thymopentin from multivesicular liposome in PBS
      (pH 7.4) and in plasma was found to be in a sustained manner. The release curves
      were fitted to Higuchi equation. The pharmacokinetics following intramuscular
      injection of the multivesicular liposome of thymopentin labeled with fluorescein
      isothiocyanate in rats showed that the peak concentration of thymopentin was
      lower and elimination of it was slower significantly than that of thymopentin
      labeled with fluorescein isothiocyanate solution in the same dose. The plasma
      concentration of thymopentin maintained above quantitative limitation at 120 h
      after administration of multivesicular liposome of thymopentin. The optimized
      formulation and preparation technology of multivesicular liposome of thymopentin
      with higher entrapment efficiency are feasible with good reproducibility.
      Multivesicular liposome of thymopentin showed significant sustained-release
      property following intramuscular injection in rats.

PMID- 18819483
TI  - [Preparation and liver targeting of floxuridinyl dibutyrate solid lipid
      nanoparticles].
AB  - This paper described the preparation and liver targeting traits of new solid
      lipid nanoparticles (SLN) containing floxuridinyl dibutyrate (FUDRB) modified
      with beta-D-galactosides (G2). FUDRB-SLN and FUDRB-G2SLN were prepared by thin
      layer ultrasonic technique. Transmission electron microscopy micrograph analysis
      demonstrated that the particle sizes of FUDRB-SLN and FUDRB-G2SLN were (137.5 +/-
      11.1) nm and (95.0 +/- 10.7) nm. Drug loading were 9.64% and 8.56%, and
      entrapment efficiency were 99.81% and 96.23%, respectively. The concentrations of
      floxuridine (FUDR) in serum and some organs (liver, kidney and lung) were
      determined by RP-HPLC after iv administration of SLN. FUDR release was confirmed,
      and a significant enrichment of SLN modified with G2 was observed in liver with
      G2 complex (targeting rates of SLN-G2 was 8.28 for liver) in comparison with FUDR
      sol (targeting rate was 2.56). FUDR could be detected in liver in mice at 480 min
      after iv administration of FUDRB-G2SLN. These results suggested that
      incorporation of G2 (4%-5%, g/g) into SLN enhanced the liver targeting-ability of
      FUDRB. SLN containing G2 could be a useful drug carrier system for liver
      targeting.

PMID- 18819484
TI  - [Optimizing expression and purification of recombinant Salvia miltiorrhiza
      copalyl diphosphate synthase protein in E. coli and preparation of rabbit
      antiserum against SmCPS].
AB  - The expression plasmid pET32CPS harboring SmCPS gene was transformed into E. coli
      BL21 trxB (DE3) resulting in recombinant strain E. coli [pET32CPS]. The induction
      of E. coli [pET32CPS] in different temperatures, induction time, IPTG
      concentrations and A600 values of E. coli were performed. The optimal expression
      conditions of SmCPS were characterized according to the orthogonal analysis, and
      the ratio of the interest protein to total proteins reached to 35.6%. The
      recombinant SmCPS protein purified by Ni2+ affinity chromatography column was
      identified by SDS-PAGE and Western blotting, and then used for rabbit
      immunization. The titer of the rabbit antiserum against SmCPS was about 1:24 300
      after the third immunization, and could specifically recognize the antigen of
      SmCPS protein by Western blotting analysis. The successful preparation of
      polyclonal antibody against SmCPS laid a foundation for further correlative study
      between expression of SmCPS and the production of tanshinones in protein level.

PMID- 18819485
TI  - [The paracrine and autocrine of stem cells: a new frontier of basic and clinical
      research].
AB  - It is found recently that stem cells possess paracrine/autocrine function. This
      review discusses the bioactive substances secreted by stem cells, including
      growth factors, cytokines, and regulatory peptides, summarizes the factors
      regulating the functions of the stem cells, such as ischemia (hypoxia), growth
      factors, sex, and other hormones. The significance of paracrine/autocrine
      function of stem cells in angiogenesis and cytoprotection in myocardium, liver,
      kidney, and nerve system is also reviewed. These data indicate that stem cells
      act in a paracrine/autocrine manner to affect the structure and function of
      target organs, and the tissue repair in pathological situation, which is one of
      the mechanisms whereby the stem cells act to improve the function of target
      organs, anti-apoptosis and anti-inflammation.

PMID- 18819486
TI  - [Extracellular matrix, matrix-degrading proteases and vascular calcification].
AB  - Vascular calcification is a common phenomena among atherosclerosis, diabetes,
      chronic kidney failure and aging. Recently, extensive researches have shown that
      the mechanisms of vascular calcification share great similarity with
      physiological mineralization rather than a passive deposition of calcium and
      phosphate. As a major component of blood vessels, the extracellular matrix (ECM)
      proteins not only provide a scaffold for normal vasculature, but also regulate
      the attachment, proliferation, migration and differentiation of vascular cells
      through ECM-cell interaction. Furthermore, it also serves as a reservoir for
      growth factors or cytokines. Previous studies have indicated the potential
      importance of ECM and ECM degrading proteases during vascular calcification.
      Extracellular matrix not only provides a major site for calcium and phosphate
      deposition, but also actively participates in the process of calcification
      through an accelerating or inhibitory effect. Multiple extracellular matrix
      proteins have been altered during the calcification. The disturbance of the
      delicate balance of ECM homeostasis may affect the evolution of vascular
      calcification. On the other hand, matrix degrading proteases (such as MMPs) may
      be involved in the occurrence and development of vascular calcification by
      affecting matrix or non-matrix substances (such as cytokines or growth factors).
      The current review summarizes the recent advance on vascular calcification in the
      context of ECM and MMPs.

PMID- 18819487
TI  - [Variational structure and function of products from IGF-1 gene].
AB  - The IGF-1 gene, containing six exons, is characterized by the generation of
      multiple heterogeneous mRNA transcripts and translations. The IGF-1 isoforms
      being produced arise from the combination of multiple transcription initiation
      sites, alternate splicing, and different polyadenylation signals. These different
      mRNAs are translated to distinct circulating and local isoforms. The circulating
      mature IGF-1 is encoded by exons 3 and 4, and its biological function in growth
      and development has been intensively studied. The local isoforms of IGF-1
      contains the part encoded by exons 3 and 4, and moreover the alternate extension
      peptide at carboxy-terminal, encoded by exons 5 and 6, is also included in the
      isoforms. And the functions of local IGF-1 isoforms and E-peptides have been
      overlooked until recently. Recently investigation shows that cell discrepant
      response to the overexpression of different IGF-1 isoforms and the E-peptides,
      and more interestingly, IGF-1Ea, IGF-1Eb (MGF) and MGF E-peptide have potential
      to promote skeletal muscle regeneration, to prevent cardiac muscle loss and
      neural damage. The acting mechanism of IGF-1 isoforms differ from the IGF-1, and
      the isoforms functioned probably by binding to specific E-peptide receptor,
      instead of binding to the IGF-1R.

PMID- 18819488
TI  - [COX plays a pivotal role in the progressive neuronal loss in neurodegenerative
      diseases].
AB  - Cyclooxygenase (COX) is the major target of non-steroidal anti-inflammatory drugs
      (NSAIDs). Since its discovery in the early 1990s, COX has been identified as a
      major player in inflammatory reactions. "neuroinflammation" is triggered and
      sustained by activation of resident cells, particularly microglia. Intensive
      researches have been made in the last decade concerning the COX pathway and its
      effect on microglial activation as well as other processes involved in
      neurondegeneration. This article reviewed new data in this area, focusing on
      three major neurodegenerative diseases, Alzheimer's disease (AD), Parkinson's
      disease (PD) and amyotrophic lateral sclerosis (ALS). By highlighting current
      knowledge in this field, it may reveal novel insight into disease mechanisms and
      help to design better therapies for these disorders.

PMID- 18819489
TI  - [The influence of psychoactive substance on histone acetylation modification].
AB  - Psychoactive substance abuse and addiction have increasingly become severe, which
      are not only a serious social problem, but an important medical problem as well.
      Recent studies have demonstrated that the histone acetylation modification is an
      important epigenetic mechanism of gene regulations and plays essential roles in
      psychoactive substance abuse and addiction. The present review mainly presents
      the influence of several psychoactive substances, including cocaine, amphetamine,
      methamphetamine, morphine, and alcohol, on histone acetylation modification.

PMID- 18819490
TI  - [Progress in the research of stanniocalcin].
AB  - Stanniocalcin (STC) is a glycoprotein hormone first identified in bony fish in
      which it regulates calcium and phosphate homeostasis. Stanniocalcin is also
      identified in human and mammals and is named STC1 and STC2 by the sequence of
      finding. There are two forms of STC produced by the STC1 gene; a 50 kD
      polypeptide known as STC50 and a group of higher molecular weight variants that
      are collectively referred to as big STC. Both STC1 and STC2 are widely expressed
      in various tissues. STC is identified as a novel marker for human cancer and
      plays an important role in heart disease, transendothelial migration of
      inflammatory cells, embryo implantation and decidualization.

PMID- 18819491
TI  - [Progress in signal transduction pathways mediating effects of angiotensin II in
      endothelial cells].
AB  - Angiotensin II (Ang II) not only mediates the effects of vasoconstriction and
      blood pressure regulation, but is also implicated in inflammation, endothelial
      dysfunction, atherosclerosis, hypertension and congestive heart failure. Ang 1I
      activates pathways of MAPK, NADPH and ROS, non-receptor tyrosine kinases and
      receptor tyrosine kinases via AT1 receptor to produce various effects involved in
      regulation of endothelial functions, endothelial dysfunction and vascular
      inflammation response.

PMID- 18819492
TI  - [The advances of the drug therapy for pulmonary fibrosis].
AB  - Idiopathic pulmonary fibrosis is a relentlessly progressive and typically fatal
      interstitial lung disease that harms human life severely. Half of patients
      diagnosed as idiopathic pulmonary fibrosis live no more than three years. No
      therapy has been clearly shown to prolong survival. Multiple new targets for
      pulmonary fibrosis have been indicated based on the researches that uncover the
      molecular and cellular mechanisms for fibrogenic diseases. In this review, we
      will summarize the clinical treatment for pulmonary fibrogenic diseases and new
      drugs with clinic trail, and then review focally the prospects of new drugs for
      pulmonary fibrogenic diseases that target alveolar epithelial cells or
      myofibroblast, inhibit the angiogenesis, regulate the balance of TH1/TH2
      cytokines or block oxide stress.

PMID- 18819493
TI  - [Progress and research in estrogen receptor polymorphisms and breast cancer
      susceptibility].

PMID- 18819494
TI  - [Functions of AQP4 in nervous system].

PMID- 18819495
TI  - [Role of HCN channel in central nervous system].

PMID- 18819496
TI  - [Roles of PPAR-delta in atherosclerosis].

PMID- 18819497
TI  - [Structure, functions and metabolisms of antizyme inhibitor].

PMID- 18819498
TI  - [Relationship between FACL4 and non-specific X-linked mental retardation].

PMID- 18819499
TI  - [Progress in research of TROY, a member of TNF receptor superfamily].

PMID- 18819500
TI  - [The signal transduction pathway and epigenetic pattern in learning and memory].

PMID- 18819501
TI  - [Heat shock protein 60 in cell apoptosis].

PMID- 18819502
TI  - [Structure and function of alternative splicing isoforms of HIF-1alpha].

PMID- 18819503
TI  - [Roles of progesterone-regulated genes in embryo implantation].

PMID- 18819504
TI  - [Physiological property and regeneration capacity of corneal endothelial cells].

PMID- 18819505
TI  - [Stop smoking advice for patients who smoke: feasible in the dental practice?].
AB  - Smoking may cause periodontal diseases and raises the chance of getting oral
      cancer. The Dutch Guideline for the Treatment of Tobacco Addiction recommends
      that dental professionals explicitly advise all patients who smoke to stop
      smoking. In 12 dental practices a study was made of how the guidelines could be
      implemented. The strategy consisted of a patient protocol for minimal, one-time
      cessation advice or for more intensive supervision, a patient leaflet,
      centralized training for the dental team, and repeated monitoring with feedback
      on the patients' experience of the behaviour that they have been advised to
      follow. Before the training and again 3 months after, professionals (n = 38) and
      an a-select sample of smoking patients (n = 197) completed questionnaires. A
      majority of patients was receptive to cessation advice of a dentist (95%) or
      counseling (68%). After 3 months it appeared that patient behaviour as reported
      by patients with respect to all points of the patient protocol had significantly
      improved.

PMID- 18819506
TI  - [Influence of sports on saliva].
AB  - Physical exertion, such as practicing sports, may have an influence on the
      secretion and composition of saliva. As a result of intensive physical exertion,
      the saliva immunoglobulin concentration decreases and the concentration of
      protein--the output of protein (mg/min), however, remains constant--and the
      viscosity of the saliva increase, while the watery secretion decreases. Moreover,
      saliva testosterone levels decrease and salivary cortisol levels increase. The
      saliva Na+, K+, Ca2+ and PO4(3-) concentrations increase slightly or remain
      unchanged. After a single physical exertion, the alterations are reversible and
      the values return to baseline within a few hours. In the case of long lasting
      intensive physical exertions, for instance lasting several months, particularly
      the decrease in the concentration of the most prevalent immunoglobulins in saliva
      (s-IgA) seems to have a more permanent character. This has a detrimental effect
      on the immunological defence, which may reduce oral as well as upper respiratory
      tract health. Complaints about this are not uncommon among serious athletes who
      are active at a high competitive level. Among these athletes, the combination of
      changes in the composition and secretion of saliva, together with intense mouth
      breathing and an adjusted diet and drinking habits carry a higher risk of
      developing caries and erosion. However, in case of decent oral health selfcare,
      the detrimental effects on oral health can be prevented.

PMID- 18819507
TI  - [Does orthodontic treatment contribute to oral health?].
AB  - The first part of this article is an edited Dutch summary of the paper "Oral
      health-related benefits of orthodontic treatment" by Donald J. Burden in the
      special issue''Orthodontics: quality of care, quality of life'' in Seminars in
      Orthodontics (June 2007). Burden carried out a systematic review of the
      literature on some, historically claimed, beneficial influences of orthodontic
      treatment, such as reduced susceptibility to dental caries, periodontal disease,
      temporomandibular dysfunction, and traumatic injury. Based on the results of this
      review, Burden concludes that the oral health benefits of orthodontic
      intervention have not been demonstrated. The second part is a critical and
      balanced commentary on the content of the paper and on Burden's conclusions.

PMID- 18819508
TI  - [Recommendations in oral implantology].
AB  - Oral implantology is a fast growing and dynamic specialization. An increasing
      number of dental professionals are carrying out oral implant treatments.
      Recommendations for oral implant treatments are needed to improve and manage
      treatment quality. In this article recommendations are proposed for 4 oral
      implant and superstructure indications in patients without complicating factors.
      The 4 oral implant indications are a mandibular complete overdenture, a maxillary
      complete overdenture, a single crown in the maxillary aesthetic region, and
      crowns and fixed partial dentures in the non-aesthetic region. The
      recommendations are also related to diagnostics and aftercare.

PMID- 18819509
TI  - [Two unusual ulcers in one patient].
AB  - A 39-year-old Antillean woman was referred by her family doctor to an oral and
      maxillofacial surgeon because of an unusual and painful ulcer in the buccal
      region of the first left mandibular molar. Earlier that day, she was diagnosed as
      HIV-positive. The ulcer was diagnosed as an atypical necrotising ulcerating
      periodontitis. Antibiotics were subscribed and after removal of the first left
      mandibular molar, the ulcer healed. After several weeks, the patient was referred
      by her internist because of another ulcer at the lateral border of the tongue.
      This ulcer was diagnosed as an eosinophilic ulcer and was healing slowly. Both
      ulcer types are seen rarely and are strongly related to immunodeficiency
      diseases.

PMID- 18819510
TI  - [The TRIP database. A valuable source of literature on oral health].
AB  - Locating the desired evidenced-based literature via the internet is usually time
      consuming and not particularly straight-forward. Websites offering evidence-based
      information should be accessible, efficient and user friendly. Many of these
      websites, however, only make their own content available, making it necessary to
      change websites in order to get a complete picture of the required information.
      The so-called website of ''Turning Research Into Practice'' is a positive
      exception. This website makes it possible to search the whole range of evidence
      based publications on a certain subject with 1 search action, is straight-forward
      and practical to use, and the presentation is exceptionally good.

PMID- 18819511
TI  - Considerations of the behaviour of C18-chains and calixarenes and their
      application for determination of stationary phase volume in RP-chromatography.
AB  - The volume of stationary phase is extremely important for the estimation of
      thermodynamic information such as entropy and Gibbs free energy in HPLC. However,
      the definition of this volume strongly depends on the conditions chosen. In the
      present mini review the partitioning model of small molecules at low
      concentrations and methanol as modifier is assumed. All the other conditions that
      could influence the volume of the stationary phase like the thickness of the
      phase, the area of the phase, the order of C18-chains, the density of the chains,
      the temperature etc. had to be considered and are therefore reviewed in the
      present work. The results of the theoretical considerations and a new method of
      surface estimation were used to calculate the stationary phase volume.

PMID- 18819512
TI  - NIR spectroscopic investigation of two fluoroquinolones, levofloxacin and
      ofloxacin, and their tablets for qualitative identification of commercial
      products on the market.
AB  - A rapid and nondestructive identification method for ofloxacin (OFLX) and
      levofloxacin (LVFX) utilizing diffusion reflectance near-infrared (NIR)
      spectroscopy was developed. An obvious difference in spectral patterns between
      LVFX that is used for commercial tablets and LVFX HCl that can be purchased as a
      reagent at a low price was also observed. These quinolones are especially
      important for use as drugs against bio-terrorism because of their effectiveness
      against anthrax infection. Therefore, the possibility of a distribution of
      counterfeit drugs containing LVFX HCl on the market would be expected. NIR
      spectroscopic analysis would be applicable to on-site quality analysis that can
      be carried out easily and nondestructively.

PMID- 18819513
TI  - Sub-second adsorption for the pico-molar monitoring of diltiazem in
      pharmaceutical preparations by fast Fourier transformation with the use of
      continuous cyclic voltammetry at an Au microelectrode in a flowing system.
AB  - Diltiazem was determined at the sub-nanomolar level for the first time by a new
      technique, involving fast Fourier continuous cyclic voltammetry in a flow
      injection system. The best performance was achieved with the basic parameters
      being set at pH value of 2.0, scan rate value of 35 V/s, accumulation potential
      of 300 mV and accumulation time of 0.8 s. This paper additionally introduces a
      special computer based numerical method for the calculation of the analyte signal
      and the noise reduction. Concerning the electrode response calculations were
      carried out according to the partial and total charge exchanges on the electrode
      surface after subtraction of background current from that of noise. Furthermore,
      to obtain a sensitive determination, the currents integration range included all
      potential scan ranges, even oxidation and reduction of the Au surface electrode,
      during the measurements. In general, the potential waveform includes the
      potential steps for cleaning, accumulation and the step of the potential ramp of
      the analyte. This potential waveform was applied to an Au disk microelectrode in
      a continuous way. Finally, the method was found to be linear for the
      concentration range of 1-41450 pg/ml (r = 0.9986), while showing a limit of
      detection and quantitation of 0.29 and 1 pg/ml, respectively.

PMID- 18819514
TI  - Extractive spectrophotometric determination of TRODAT-1 hydrochloride in
      lyophilized kit.
AB  - A simple, sensitive, and accurate spectrophotometric method has been developed
      for the assay of TRODAT-1 hydrochloride in lyophilized kit. The method is based
      on the formation of ion-pair association complex of TRODAT-1 with bromothymol
      blue (BTB) in disodium hydrogen phosphate/citric acid buffer of pH 4.0. The
      colored product was extracted with chloroform, and measured
      spectrophotometrically at 414 nm. Beer's law was obeyed in the range of 5-25
      microg/ml with molar absorptivity of 2.75 x 10(4) l/mol/cm. Optimization of
      experimental conditions was described for the method. The proposed method has
      been successfully applied for the analysis of TRODAT-1 hydrochloride in
      lyophilized kit. No interference with pharmaceutical excipients was observed.

PMID- 18819515
TI  - UV-spectrophotometric determination of imatinib mesylate and its application in
      solubility studies.
AB  - A new, simple and sensitive UV-spectrophotometric method was developed for the
      determination of imatinib mesylate in bulk and pharmaceutical formulations
      (tablets and nanoparticles). The developed spectroscopic method was validated for
      selectivity, linearity and range, precision, accuracy and sensitivity. The method
      has demonstrated excellent linearity over the range of 2.5-25 microg/mL with
      regression equation: absorbance (AU) = 0.047 x concentration (microg/mL) + 0.008
      and r2 = 0.9998. The developed method demonstrated consistent high recoveries (99
      102%) and low relative standard deviation (< 5%) at 285 nm. Moreover, the method
      was found to be highly sensitive with low limit of detection (0.57 microg/mL) and
      limit of quantitation (1.71 microg/mL). The apparent molar absorptivity and
      Sandell's sensitivity was found to be 2.75 x 10(3) L/M cm and 2.15 microg/cm2
      respectively. The validated method was successfully employed for the drug content
      analysis from tablets and nanoparticles preparations. Additionally, the method
      was successfully employed for pH metric solubility analysis of the drug.

PMID- 18819516
TI  - Liposome-based intracellular kinetics of doxorubicin in K562/DOX cells.
AB  - Liposomes can improve the intracellular concentration of cytotoxic drugs, and are
      regarded as a possible pharmacological approach to overcome drug resistance. The
      kinetic analysis of subcellular drug uptake and efflux helps to elucidate the
      resistance mechanism which is associated with the ATP-dependent membrane
      transporter P-glycoprotein (P-gp). However, there are only few reports about the
      intracellular kinetics of liposomes. In this work, the kinetics of drug uptake
      and active efflux of doxorubicin (DOX) encapsulated in liposomes in both intact
      cells and nuclei were studied using P-gp expressing K562/DOX cells. The results
      show that liposomes enhanced drug accumulation in intact cells and nuclei, and
      improved DOX retention in nuclei after withdrawal. Furthermore, the nuclei levels
      of liposomal drug rose slowly and reached a plateau after 2 h incubation, whereas
      the free drug reached the plateau in 15 min, suggesting that it takes time for
      the liposomes to get from the cytoplasm to the nuclei. Our results demonstrated
      that liposomes not only increase DOX levels allocated to nuclei but also extended
      retention in the nuclei of resistant cells.

PMID- 18819517
TI  - Insulin availability from mucoadhesive tablets.
AB  - The widespread implementation of peptides as drugs encounters numerous obstacles,
      the main being invasive and inconvenient parenteral administration. Oral
      transmucosal administration is one of the possible alternatives, valuable for its
      noninvasiveness and easy accessibility. The aim of our study was to determine the
      implementation possibilities of mucoadhesive tablets prepared on a
      methylcellulose and sodium alginate basis with an addition of absorption
      modifying hyaluronic acid, as carriers for peptides destined for oral
      transmucosal administration. Two series of 50 mg tablets containing 5mg of
      insulin were prepared for the study. The first series contained methylcellulose,
      hyaluronic acid and mannitol, while the second series' formulation included
      sodium alginate, hyaluronic acid and mannitol. Carried out study confirmed that
      insulin administration in the form of mucoadhesive tablets lowers blood glucose
      levels in rabbits. Better effects were reached in vivo in the case of MC-based
      tablets, for which stronger and longer glycemia lowering was achieved.

PMID- 18819518
TI  - Preparation, characterization and optimization of probucol self-emulsified drug
      delivery system to enhance solubility and dissolution.
AB  - The main purposes of this work were to prepare, characterize and optimize a self
      emulsified drug delivery system of probucol (PBSEDDS) with enhanced dissolution
      and better chance for oral absorption. The methods included determination of the
      solubility of probucol in different oils, surfactants and co-surfactants using
      saturation solubility method and HPLC for drug analysis. The ingredients showing
      high drug solubility were used to prepare PBSEDDS after being tested for physical
      and chemical compatibility with the drug using DSC and FTIR. The prepared
      formulations were evaluated for droplet size, turbidity, spontaneity of
      emulsification and dissolution in water. Optimization was performed using a three
      factor, three-level Box-Behnken experimental design. The results showed high drug
      solubility and compatibility with soybean oil (solvent), Labrafil M1944CS
      (surfactant) and Capmul MCM-C8 (cosurfactant). Oil to surfactant/co-surfactant
      ratio showed large influence on the characteristics of PBSEDDS. Several fold
      improvement of drug dissolution was observed compared to drug solution in soybean
      oil alone. Optimization study showed that observed and predicted values of
      cumulative percent drug dissolution after 60 min were in reasonable agreement.
      The experimental design applied helped in understanding the effects and the
      interaction effects between the independent factors. The prepared PBSEDDS may
      have the potential to enhance the therapeutic bioavailability of probucol.

PMID- 18819519
TI  - Enhanced oral bioavailability of salvianolic acid B by phospholipid complex
      loaded nanoparticles.
AB  - With a simple and feasible method, a salvianolic acid B-phospholipid complex was
      prepared to increase the absorption of salvianolic acid B in the gastrointestinal
      (GI) tract. Because the solubility of the complex in water was very poor, the
      complex was encapsulated into nanoparticles to facilitate its administration. The
      physicochemical properties of the complex were investigated by differential
      scanning calorimetry (DSC), infrared scanning, ultraviolet scanning and X-ray
      diffraction (XRD), and the solubility of salvianolic acid B and the complex in
      water or n-octanol was measured. The pharmacokinetic characteristics and
      bioavailability were compared after oral administration of salvianolic acid B
      (500 mg/kg) and the complex nanoparticles (450 mg/kg equivalent to salvianolic
      acid B). The results proved the drastic decrease in the solubility of salvianolic
      acid B in water after successful formation of the drug-phospholipid complex.
      After oral administration the peak plasma concentration (Cmax) of salvianolic
      acid B given by the complex nanoparticles was 3.4 microg/ml which was much higher
      than that of salvianolic acid B sample (Cmax = 0.9 microg/ml), with Tmax of 75
      min, 45 min and AUC of 664, 257 microg/ml min, respectively. The relative
      bioavailability (F) reached 286%.

PMID- 18819520
TI  - Evaluation of the toxicity of oligonucleotide/cationic nanoemulsion complexes on
      Hep G2 cells through MTT assay.
AB  - The purpose of this study was to evaluate the toxicity of the
      oligonucleotide/cationic nanoemulsion complexes on Hep G2 cells through MTT
      assay. Complexes exhibit droplet size, zeta potential and viscosity of
      approximately 270 nm, +50mV, and 1.0 cP. Different parameters which may have an
      influence on toxicity results obtained by MTT assay, i.e. cells number,
      concentration of MTT reagent and the addition of Soerensen's glycine buffer were
      first evaluated. In the optimized conditions (1 x 10(4) cells and 0.5 mg/mL MTT),
      the overall results showed that the addition of increasing amounts of complexes
      (or nanoemulsions) lead to a progressive toxicity on cells attributed to the
      presence of the cationic lipid stearylamine in the formulations, whatever the
      medias's pH is. The IC50 was approximately 200 microg/ml. Such results open
      interesting perspectives on the use of these nanoemulsions as oligonucleotide
      delivery systems for Hep G2 cells.

PMID- 18819521
TI  - Inhibitory effect of a novel resveratrol derivative on nitric oxide production in
      lipopolysaccharide-activated microglia.
AB  - Excessive nitric oxide (NO) production by activated microglial cells has been
      implicated in various neurodegenerative diseases. In the present study, we found
      that a new resveratrol derivative, (E)-5-(3-nitrostyryl)benzene-1,3-diol (RV06),
      has a more potential inhibitory effect on the production of NO in LPS-activated
      N9 microglial cells, and the result was confirmed on primary rat microglial
      cells. Further studies showed that RV06 inhibited LPS-induced iNOS expression in
      N9 microglial cells, with no activity on direct scavenging nitric oxide radical
      in a cell-free environment. The results suggest that RV06 might be a potential
      anti-inflammatory agent or leading compound which can inhibit inflammatory
      responses of microglia.

PMID- 18819522
TI  - Effect and mechanism of nociceptin/orphanin FQ reversing multi-drug resistance in
      K562/ADM cell.
AB  - OBJECTIVE: To investigate the effect and mechanism of nociceptin/orphanin FQ
      (OFQ) reversing multi-drug resistance of K562/ADM cells in vitro. METHODS: MTT
      assay, Wright staining, flow cytometry, transmission electron microscope and gel
      electrophoresis were used to evaluate the effect and mechanism of OFQ in
      reversing multi-drug resistance of K562/ADM cells. RESULTS: OFQ could time
      dependently reverse the ADM resistance of K562/ADM cell. After treatment with OFQ
      (1 x 10(-7) mol x L(-1)), K562/ADM cells were cultured for 24, 48 and 72 h. The
      reversal index (RI) was 1.33, 1.42 and 1.53, respectively. Furthermore, OFQ
      significantly increased the intracellular accumulation of ADM in K562/ADM cells
      and percentage apoptosis in K562/ADM cells. OFQ down-regulated the level of P-gp
      time-dependently, while the level of Fas and FasL were up-regulated. There were
      evidently significant differences compared with the control (P < 0.01). After
      treating K562/ADM cells with OFQ (1 x 10(-7) mol x L(-1)) and ADM (20 microg x
      ml(-1)) for 48 hours, the cells showed apoptotic nuclear fragmentation, which was
      characterized by the appearance of a DNA ladder pattern in genomic DNA gel
      electrophoresis. CONCLUSION: OFQ can reverse the ADM resistance of K562/ADM
      cells. The mechanism involves OFQ up-regulating the expression of Fas/FasL, down
      regulating the level of P-gp, and decreasing the intracellular level of calcium
      in K562/ADM cells.

PMID- 18819523
TI  - Immunogenicity of lipid sustained release implants containing imiquimod, alpha
      galactosylceramide, or Quil-A.
AB  - The aim of this study was to investigate and compare the immunogenicity of
      liposome-forming, sustained release lipid implants containing either an alpha
      galactosylceramide (alpha-GalCer) analogue, imiquimod or Quil-A (QA) as
      adjuvants. Ovalbumin (OVA) was used as a model antigen. Groups of C57Bl/6 mice
      were subcutaneously immunised with lipid implants containing one of the
      adjuvants, or inoculated with OVA in alum. The expansion of CD8+ and CD4+
      transgenic T cells was analysed to assess the ability of these implants to
      stimulate cell-mediated immunity. In addition, the production of OVA-specific IgG
      antibodies was determined. QA-containing lipid implants were more efficient in
      the stimulation of CD8+ T cells and IgG antibodies than the two immunomodulators
      alpha-GalCer and imiquimod. These results suggest that, using this
      immunisationprotocol and dose of immunomodulators, QA was superior to imiquimod
      and alpha-GalCer.

PMID- 18819524
TI  - The aldose reductase inhibitory capacity of Sorbus domestica fruit extracts
      depends on their phenolic content and may be useful for the control of diabetic
      complications.
AB  - Aldose reductase (ALR2) is a rate-limiting enzyme in the polyol pathway
      associated with the conversion of glucose to sorbitol and whose activity is
      implicated in the development of the long-term diabetic complications. Upon
      previous years, several scientific efforts were focused towards the development
      of ALR2 inhibitors as effective secondary anti-diabetic drugs. To this regard and
      during our extensive phytochemical analysis of Sorbus domestica (fam. Rosaceae),
      twenty nine different extracts, fractions and residues of five different maturity
      stages of Sorbus domestica fruits were evaluated for their in vitro ALR2
      inhibitory capacity. The data obtained thus far have indicated that the diethyl
      ether and ethyl acetate fractions possess high aldose reductase inhibitory
      activity. Furthermore, detailed phytochemical LC-DAD-MS (ESI+) analysis of such
      extracts has shown that this aldose reductase inhibitory activity could be
      attributed to the high content of flavonoids and hydroxycinnamoyl esters. These
      results suggest that Sorbus domestica fruit consumption may be a promising way
      for lowering the incidence of long-term complications of diabetes mellitus,
      especially at early stages, a possibility being discussed in this paper.

PMID- 18819525
TI  - Variations in nutrient concentration and phytoplankton composition at the
      euphotic and aphotic layers in the Iranian coastal waters of the Southern Caspian
      Sea.
AB  - Temporal variations and regional distributions of dissolved nutrients and their
      elemental ratios in the Iranian coastal waters of the Southern Caspian Sea were
      investigated. The data were collected in 1996-97 (Phase I, as a background data
      and undisturbed ecosystem) and in 2005 (Phase II, as a disturbed ecosystem) at
      sampling points (from 10 to 100 m depths). In addition to the two main sampling
      exercises, additional sample collections were carried out during the period of
      1994 to 2004 as a long-term study. This study showed that the dissolved inorganic
      nitrogen/dissolved inorganic phosphorus (DIN/DIP) ratios in the southern Caspian
      Sea vary within a very narrow range (4.47 to 5.78) within the euphotic and
      aphotic layers and is by one order of magnitude lower than what have been
      reported for several other marine ecosystems. Phytoplankton growth seems to be
      nitrogen limited while the levels of P and Si always remain high. Factor
      Analysis/Principal Component Analysis (FA/PCA) of the correlation matrix showed
      that the nitrogen compounds are associated with the main factor accounting for
      25.7-26.2% of the total variance for both the sampling periods. During Phase I,
      the Chrysophyta were the major group, whereas during Phase II the proportion of
      Chrysophyta in the total community progressively decreased, while the other
      groups increased.

PMID- 18819526
TI  - Effects of haemorrhage on thermoregulation, heart rate and blood constituents in
      goats (Capra hircus).
AB  - The effects of two levels of bleeding (15 and 30%) on physiological responses
      were evaluated in adult goats. The magnitude of haemorrhage was expressed as
      percentage of initial total blood volume after plasma volume determination by dye
      dilution. The groups subjected to haemorrhage had higher rectal temperature,
      respiration rate and heart rate compared to the control; the responses were more
      marked with the higher level of bleeding. The treated groups had lower Packed
      Cell Volume (PCV), haemoglobin concentration (Hb) and Total Leucocyte Count (TLC)
      compared to the control; they were significantly lower with high level of
      bleeding compared to the control. The ratio of lymphocytes decreased, whereas the
      neutrophil ratio increased in treated groups compared to the control. The treated
      groups had lower serum total protein and albumin concentrations compared to the
      control. The plasma glucose level was higher in treated groups compared to the
      control and it increased with the increase of bleeding level. The treated groups
      had lower serum Na, Ca and Mg concentrations compared to the control. The levels
      of these minerals decreased with increase of bleeding level. The 15% bleeding
      group returned to normal values within 2 weeks, whereas the 30% bleeding group
      recovered within 5 weeks.

PMID- 18819527
TI  - Chemotaxonomic studies on Aegilops L. (Poaceae) in Iran.
AB  - This study, using seed storage protein electrophoresis, evaluates the taxonomic
      status of the Aegilops L. species and the variation between the species.
      Therefore, with the seeds of seven species and 46 accessions of Aegilops, the
      prolamin was separated. On the base of the banding patterns, the cluster analysis
      among these species was studied. The results of this study show that most of the
      tetraploid species (2n = 4x = 28; x = 7) and the diploid species (2n = 2x = 14; x
      = 7) were grouped with each other. This document illustrates that a high gene
      flow exists among the diploid species. Further, high variability was observed
      among the accessions of Aegilops species. Morphologically; some of the species,
      which are very similar (Ae. umbellulata Zhuk., Ae. columnaris Zhuk.), have
      exactly been distinguished in this method. Chemo taxonomically, the status of
      these species was partially illustrated. Finally, Prolamin is an appropriate
      marker for identifying the taxonomic position of Aegilops species.

PMID- 18819528
TI  - Effect of harvesting index on browning reaction and changes of tissue structure
      in santol fruits.
AB  - This investigation was carried out to justify the relationship between harvesting
      ages of santol fruit, browning reaction and other concerning data. Growers of
      santol plantations in Thailand have always accustomed to problems on
      inconsistency in qualities of santol fruits var. Pui Fai due to inappropriate
      harvesting index. Thus these encourage to decrease marketable qualities of fruits
      and short shelf-life particularly browning discoloration. In order to investigate
      adequate information for growers of the santol orchard plants, it is important to
      carry out experiments on Polyphenol Oxidase (PPO) activity and changes of tissue
      structure by separating fruit into three parts: peel, flesh and seed of santol
      fruit var. Pui Fai harvested at four stages: 100, 115, 130 and 145 Days After
      Full bloom (DAF). A factorial in randomized complete block design with five
      replications was used. In each replication ten fruits were used. This
      investigation was carried out during the period of October 2006 to March 2007 at
      The Department of Agricultural Technology, Mahasarakham University, Northeast
      Thailand. The results showed that PPO activity which related to browning reaction
      changed with harvesting stage. The highest PPO activities were obtained and
      highly significant increased in mature fruit at 130 and 145 DAF. When the fruits
      were ripening at 145 DAF, PPO activities from peel, flesh and seed had no
      significant differences and high levels by 160.76-184.44, 158.88-180.76 and
      154.52-181.08 U mg(-1) fresh weight, respectively. While cross-section study in
      peel and flesh of santol fruit var. Pui Fai at different ages indicated that
      immature fruits (100 and 115 DAF) showed small cells arranged one to two layers
      in epidermis. Trichome like-hair also appeared on this layer. When santol fruits
      grew through 145 DAF, epidermis converted to periderm and trichome disappeared.
      In addition, parenchyma cells in flesh accumulated several substances in form of
      druse with the fruit age increment. These high PPO activities and fruit tissue
      conversions of peel and flesh in mature fruit may led to be more sensitive to
      browning reaction.

PMID- 18819529
TI  - Expression of biologically active measles virus hemagglutinin glycoprotein by a
      recombinant baculovirus.
AB  - In this study, one of the measles virus membrane proteins, named hemagglutinin
      (H) which has a key role in tropism, receptor binding, hemagglutinating activity
      and also induction of protective immunity against viral infection, was expressed
      by the baculovirus expression system using specific plasmid (pDONR221) to produce
      entry clone. Measles Virus (AIK-C strain) genome was extracted from infected Vero
      cells. H gene was amplified by specific primers during RT-PCR reaction and
      inserted into the specific plasmid (pDONR221) using BP recombination reaction.
      Recombinant baculovirus harboring H gene was consequently constructed by LR
      reaction. Insect cells (Sf9) were infected with recombinant baculovirus. In order
      to increase viral titer, recombinant baculoviruses were passaged four times in
      Sf9 cells. Synthesis of H protein was verified by SDS-PAGE, western-blot and
      indirect immunoflourescene using goat polyclonal antibody against Measles Virus.
      The results showed that H protein was partially glycosylated, but it appeared to
      be active in hemagglutination assay.

PMID- 18819530
TI  - Leaf and seed micronutrient accumulation in soybean cultivars in response to
      integrated organic and chemical fertilizers application.
AB  - Plant nutrients can be influenced by organic materials of soils. An experiment
      was conducted to evaluate the effect of organic amendments on elements uptake by
      soybean cultivars in a silty loam soil in Mazandaran province, Iran. The
      experiment was carried out in split plot based on randomized complete block
      design with three replications in 2006. Main plots were included 8 fertilizer
      treatments consisted of 20 and 40 Mg ha(-1) Municipal Solid Waste Compost (MSW),
      Vermicompost (VC) and Sewage Sludge (SS) which enriched with 50% chemical
      fertilizers needed by soil, only chemical fertilizer treatment and control. Sub
      plots consisted of three genotypes of soybean (032, 033 and JK). Grain yield was
      determined and soybean leaves and seeds were digested and analyzed for Mn, Cu, Zn
      and Fe. Results showed that yield and elements content in soybean leaves and
      seeds (Mn, Cu, Zn and Fe) were influenced by all treatments. The 40 Mg ha(-1) of
      sewage sludge enriched with chemical fertilizers produced maximum grain yield.
      Different soybean cultivars had also significant differences in terms of leaf and
      seed micronutrients accumulation. Maximum grain yield was observed in JK and 033.
      Mean comparisons showed that interaction effects of fertilizer and cultivar had
      significant differences on Mn, Cu and Fe content in soybean leaves, so that the
      maximum Cu content was observed in 032 cultivars with 40 Mg ha(-1) enriched
      sewage sludge and municipal waste compost. Also the highest amount of Fe was
      obtained for JK cultivar when the 40 Mg ha(-1) of municipal compost was used.
      Among different mentioned traits, Fe and Cu content in leaf and seed and Zn
      content in leaf had a positive and significant correlation with grain yield.

PMID- 18819531
TI  - Every-other-furrow irrigation with different irrigation intervals for grain
      sorghum.
AB  - The water stress effects caused by every-other-furrow irrigation on yield may be
      alleviated by more frequent irrigation intervals. This research was conducted to
      determine yield and water use efficiency of grain sorghum under fixed and
      variable every-other-furrow and every furrow irrigations at different irrigation
      intervals and shallow and deep water table conditions. Water needs of grain
      sorghum grown on a fine-texture soil may not be met by using Every-Other Furrow
      Irrigation (EOFI) especially under 15 and 20 day irrigation intervals. The water
      stress decreased the grain yield mainly through decreasing the number of grains
      per cluster and in a lesser degree by decrease in 1000-seed weight. The clay soil
      with a layer of high clay content at depth of 70-100 cm and shallow water table
      may restrict the root growth and consequently the longer irrigation intervals
      with greater soil water stress can cause lower grain yield in these conditions.
      However, more frequent EOFI using 10 day intervals has produced very similar
      results with only a marginal reduction in crop yield. Furthermore, there was no
      statistically significant difference in grain yield between fixed and variable
      every-other -furrow irrigations. In general, at given applied water, the relative
      grain yield with respect to the maximum grain yield of sorghum at EOFI was higher
      than those at EFI. At relative applied water of 85% (mild deficit irrigation),
      EOFI may be recommended to obtain the same grain yield as that of EFI with full
      irrigation. Furthermore, it may result in 23% more grain yield than that obtained
      by EFI with the same amount of applied water as deficit irrigation.

PMID- 18819532
TI  - Studies on plant regeneration and somaclonal variation in Saintpaulia ionantha
      Wendl. (African violet).
AB  - Efficient plant regeneration of Saintpaulia ionantha (African violet) has been
      obtained in the present study. MS medium supplemented with 1.0 mg L(-1) IAA and
      2.0 mg L(-1) Zeatin resulted in 100% shoot regeneration and induced the highest
      number of shoots (average 15.0 +/- 0.8 shoots per explant) after being cultured
      for 8 weeks. The above hormone combination was optimum for shoot regeneration.
      Most of Saintpaulia ionantha plantlets derived from tissue culture system could
      be hardened and transferred to the greenhouse conditions with 84.0 +/- 1.6%
      success rate. However, regenerated plantlets of Saintpaulia ionantha (even after
      12-months-old) failed to flower. Morphological characters of regenerated
      plantlets of Saintpaulia ionantha were observed and compared with in vivo
      (intact) plants. Regenerated plantlets showed some differences in morphological
      characters, such as height and leaf size, texture and colour, but the plantlets
      showed no variation in leaf arrangement and leaf margin. However, the
      morphological characters of the regenerated plantlets were found to be unstable.

PMID- 18819533
TI  - Use of CLSA and SPME-headspace techniques followed by GC-MS analysis to extract
      and identify the floral odorants.
AB  - Flowers of Ziziphus spina christi are known to be attractive for parasitoids and
      predators. In Y-tube olfactometer experiments, the dried flowers attracted
      significantly (p < 0.001) the female parasitoids Aphelinus abdominalis. The
      flower volatile compounds were analyzed to understand which compounds could be
      specifically responsible for this attractiveness. The volatile compounds of
      Ziziphus flowers were extracted by closed-loop-stripping-analysis (CLSA) and also
      by solid phase microextraction (SPME) followed by gas chromatography-mass
      spectrometry (GC-MS) analysis. The main chemical classes of the volatile
      compounds are aldehydes, monoterpene-alcohols, ketones and hydrocarbons. Flower
      extract and some specific compounds will be further tested for their
      responsiveness to predators and parasitoids in behavioural and
      electrophysiological experiments.

PMID- 18819534
TI  - Some aspects on the feeding of Gerres oblongus (Cuvier, 1830) dwelling from the
      Jaffna lagoon.
AB  - A total of 179 fishes of Gerres oblongus (Cuvier, 1830) ranging in standard
      length 40 to 169 mm were collected in the morning from four collection sites in
      the Jaffna lagoon. The stomach contents were assessed qualitatively and
      quantitatively. The fishes were placed in 19 mm size class intervals and the food
      analysis were done both by qualitatively and quantitatively. Variation of food
      with respect to month was also determined. The analysis of gut contents of G.
      oblongus showed that it is an omnivore and the preference to animal diet is
      higher than the vegetable matter. The presence of molluscs, soil particles and
      polychaetes indicated that it is a substratum feeder or feed largely on attached
      surfaces. Feeding intensity was high during February which has been reflected by
      the satiation index (8.3) in the same period. At the same time coefficient of
      condition has been fluctuated in between 2.2-3.7 except in May (4.4) indicated
      that it has slow growth rate. The mean relative gut length showed a positive
      increase with the body length. The value for the relationship between the mean
      relative gut length to body length further confirms that it is omnivorous in
      feeding habit.

PMID- 18819535
TI  - Impact of tree species on nutrient stocks in the forest floors of a temperate
      forest ecosystem.
AB  - To investigate the effect of silvicultural methods on forest floor C, N and
      elements stocks an experiment was carried out by sampling the forest floors of a
      100-120-years-old species including beech, Norway spruce and mixed beech-spruce
      at the Solling forest, Germany. While the stocks of carbon and nitrogen in the
      forest floors of pure beech and spruce were significantly influenced by species
      specific differences of litter quality (p < 0.001), no significant differences
      were detected between pure and mixed species stands. Forest floor mass, some
      elements concentrations and C/nutrient ratios were significantly affected by tree
      species differences, while no clear dependency between pH and site specific
      effects was found among pure stands. Acid element concentrations in the forest
      floors of pure spruce were remarkably higher than the values obtained at beech
      stand, while the stocks were to some extent modified in mixed silviculture. The
      base-pump effect of beech significantly controlled variation between mono
      cultures on calcium stocks, while the acidifying effect of spruce in mixtures
      resulted in modification of Ca stocks of forest floors. The status of other
      nutrient elements at mixed species cultures due to variation in nutritional
      properties and composition of litter compared to pure species were between the
      range of values observed in mono cultures.

PMID- 18819536
TI  - Applied shared log-normal frailty Cox-proportional hazard model to evaluating the
      effect of vitamin A on the rat passive avoidance memory.
AB  - In this research, the Cox-proportional hazard model is used to investigate the
      effect of various values of vitamin A (3000, 4500 and 6000 IU kg(-1)) and sesame
      oil on the passive avoidance memory of rats by shuttle box. Present results
      confirm that various values of vitamin A do not improve the passive avoidance
      memory of rats (p < 0.05). We found that the animals are clustered (p < 0.001)
      and applying shared log-normal frailty for clustering improves present results (p
      < 0.05) such that sesame oil improves the passive avoidance memory task (p <
      0.05). Therefore we should consider clustering in the analysis of biological data
      or we should use cloned animals.

PMID- 18819537
TI  - Effect of salt stress on seed germination and seedling growth of three salinity
      plants.
AB  - Seeds of three halophyte species included Limonium sinense Kuntze, Glycine soja
      sieb. and Sorghum sudanense Stapf. were used to investigate the effects of
      different salinity concentrations on their germination percentage, germination
      energy, germination index, relative germination rate, relative salt-injury rate,
      radicle length and hypocotyl length. Results showed that seeds of G. soja can
      germinate well and rapidly at lower level of salt (< 200 mmol L(-1)), 50 mmol L(
      1) salt concentrations is better to S. sudanense, suitable salt concentrations
      was beneficial to germinate of S. sudanense seeds. Seeds of L. sinense and S.
      sudanense can germinate at higher level of salt (400 mmol L(-1)). Three plant
      seeds had different physiological mechanism for germination under salt stress,
      radicle hypocotyl ratio of L. sinense and S. sudanense increased with increasing
      salt suggested that they had the higher tolerance in shoot growth under NaCl
      stress, which is perhaps the reason for their wide utilisation for saline soil
      rehabilitation.

PMID- 18819538
TI  - Mass propagation of Rauwolfia serpentina L. Benth.
AB  - A protocol for mass propagation through axillary bud proliferation was
      established for Rauwolfia serpentina L. Benth. (Apocynaceae). MS medium
      supplemented with 1.5 mg L(-1) BA and 0.2 mg L(-1) NAA elicited the maximum
      number of shoots (4 multiple shoots) from nodal explants. These adventitious
      shoots were best rooted on half strength MS medium supplemented with 1.0 mg L(-1)
      each of IBA and IAA. The in vitro raised plants were acclimatized in glass house
      and successfully transplanted to field condition with almost 95% survival.

PMID- 18819539
TI  - Estimation of combining ability for yield and yield components in rice (Oryza
      sativa L.) cultivars using diallel cross.
AB  - In order to estimate combining ability and gene action of a number of rice
      cultivars, a 5 x 5 half a diallel cross genetic design has been used. Parents and
      their hybrids have been evaluated in a randomized complete block design with 3
      replicates for yield and 6 yield components in 2007 in Rice Research Station of
      Iran-Amol. Mean squares of genotypes for all traits were highly significant (p <
      0.01). Significant mean squares of combining ability for all traits showed
      additive and non-additive effects in control of the related traits. Having
      nonsignificant MS(GCA)/MS(SCA) ratio for all traits but 1000-grain weight show
      higher importance of nonadditive effects in comparison with additive effects of
      controlling genes. High relative importance of specific combining ability
      indicated that all traits but 1000-grain weight are highly affected by impacts of
      specific combining ability. Generally, Dasht, Neda and Binam were the best
      parents for general combining ability and Binam x IR62871-175-1-10 and Mashhad
      Domsiah x Binam were the best hybrids for grain yield and its components.

PMID- 18819540
TI  - Frequency of mecA gene and borderline oxacillin resistant Staphylococcus aureus
      in nosocomial acquired methicillin resistance Staphylococcus aureus infections.
AB  - The aim of the study was to determine the frequency and type of MRSA strains and
      antibiotic susceptibility in Al-Zahra Hospital, Isfahan, Iran. In an analytic
      descriptive survey in 2005 and early 2006, patients admitted to the hospital who
      contracted S. aureus nosocomial infections were enrolled in the study. All
      isolates were identified by the conventional laboratory tests. Minimal Inhibitory
      Concentration (MIC) of oxacillin on isolated bacteria was determined by E-Test
      method. According to Clinical and Laboratory Standard Institute (CLSI) criteria
      all strains with MIC of > or = 4 microg for oxacillin were identified as MRSA.
      Intrinsic high level resistance (mecA positive) and borderline oxacillin
      resistant Staphylococcus aureus (BORSA) were detected by amoxicillin-clavulanate
      E-test strips. Strains with MIC of > or = 4 microg for oxacillin and > or = 8
      microg for amoxicillin-clavulanate were identified as mecA positive MRSA. Other
      staphylococcus with MIC > or = 4 microg for oxacillin and < or = 4 for
      amoxicillin-clavulanate were identified as mecA negative MRSA (BORSA). MIC of
      vancomycin also was determined on isolated bacteria. Data were analyzed by SPSS
      version 13 and Who net version 5. Out of 134 Staphylococcus aureus samples which
      were isolated from nosocomial infections 90 (67.2%) were MRSA. Sixty seven out of
      90 (74.5%) MRSA were mecA positive and 23 out of 90 (25.5%) were mecA negative
      (BORSA). Although most of the MRSA strains were isolated from surgical site
      infections, there were no statistically significant differences between types of
      Staphylococcus aureus growing from variant sites of infections. Only one (1.49)
      of the mecA positive MRSA had reduced susceptibility to vancomycin but all of the
      mecA-negative MRSA (BORSA) were sensitive to it. Because one fourth of our
      staphylococcus strains are mecA negative BORSA and there is no alternative for
      vancomycin against mecA positive MRSA and Enterococcus spp. in our hospital,
      vancomycin should be reserved only for life threatening infections due to these
      organisms. Thus MRSA typing should be done to choose appropriate antibiotic for
      optimal treatment of MRSA infections.

PMID- 18819541
TI  - Antibacterial activity of the fruits of Iranian Torilis leptophylla against some
      clinical pathogens.
AB  - The aim of this study was to examine the antimicrobial activity of the methanolic
      extract of Torilis leptophylla was tested on eleven bacteria (Bacillus anthracis,
      Bacillus subtilis, Bacillus pumilus, Staphylococcus aureus, Bacillus
      licheniformis, Brucella melitensis, Escherichia coli, Salmonella typhi, Proteus
      mirabilis, Bordetella bronshiseptica and Pseudomonas aeruginosa). Tested extract
      was effective against all bacteria but not B. subtilis. Consequently, the
      ethanolic extract had antibacterial activity on some pathogens thus confirming
      their use in folk medicine.

PMID- 18819542
TI  - The effect of organophosphate pesticides on the blood glucose levels in the
      mouse.
AB  - The aim of the present study was to study the effect of two selected agents of
      this group on blood glucose levels in an animal model. Forty-two adult male mice
      were divided into 7 groups of 6 each. Animals were exposed by their entire tail
      for 10 sec once a day for 7 successive days to either 0, 0.1, 1, or 10% azynphos
      methyl (AZP) malathion (MLT). On days 1,4 and 8, a small drop of blood was taken
      from tail of the animals that had been kept fasted overnight. Blood glucose
      levels were measure using a glucometer. The animals then were fed and after 1 h
      the blood glucose measurement was performed again. Results of this study
      indicated that the administration of organophosphate agents significantly
      prevented from the rise of blood glucose after feeding in comparison to the
      control animals. This reached the level of statistical significance on day 1 with
      MLT 1% (p < 0.001). It is concluded that exposure with organophosphate pesticides
      may suppress excessive blood glucose levels with no effect on the basal blood
      glucose in the fasting animals.

PMID- 18819543
TI  - Prevalence of Escherichia coli O157:H7 among diarrhoeic HIV/AIDS patients in the
      Eastern Cape Province-South Africa.
AB  - This study investigated the prevalence of Escherichia coli O157:H7 in the stool
      of confirmed and non-confirmed diarrhoeic HIV/AIDS patients. Escherichia coli
      O157:H7 was isolated by culture-based and immunomagnetic separation from three
      hundred and sixty stool swabs. Identification was by conventional IMViC, 20E API
      and molecular techniques. Confirmed and non-confirmed diarrhoeic HIV/AIDS
      patients had 56.5% (74/131) and 43.5% (57/131) respectively of E. coli O157:H7.
      Molecular results indicated that the prevalence of E. coli O157:H7 was 12.16%
      (9/74) and 8.77% (5/57) from stool swabs of confirmed and non-confirmed
      diarrhoeic HIV/AIDS patients. Antimicrobial resistance was higher for E. coli
      O157:H7 isolates from stools of confirmed HIV/AIDS than it was for non-confirmed
      HIV/AIDS patients. Escherichia coli O157:H7 might be a silent cause of diarrhoea
      in HIV/AIDS patients. It is recommended that HIV/AIDS patients with diarrhoea
      should be screened for E. coli O157:H7 and surveillance programmes for these
      bacteria should be established in both urban and rural areas of South Africa.

PMID- 18819544
TI  - Assessment of gastric cancer survival: using an artificial hierarchical neural
      network.
AB  - This study is designed to assess the application of neural networks in comparison
      to the Kaplan-Meier and Cox proportional hazards model in the survival analysis.
      Three hundred thirty gastric cancer patients admitted to and surgically treated
      were assessed and their post-surgical survival was determined. The observed
      baseline survival was determined with the three methods of Kaplan-Meier product
      limit estimator, Cox and the neural network and results were compared. Then the
      binary independent variables were entered into the model. Data were randomly
      divided into two groups of 165 each to test the models and assess the
      reproducibility. The Chi-square test and the multiple logistic model were used to
      ensure the groups were similar and the data was divided randomly. To compare
      subgroups, we used the log-rank test. In the next step, the probability of
      survival in different periods was computed based on the training group data using
      the Cox proportional hazards and a neural network and estimating Cox coefficient
      values and neural network weights (with 3 nodes in hidden layer). Results were
      used for predictions in the test group data and these predictions were compared
      using the Kaplan-Meier product limit estimator as the gold standard. Friedman and
      Kruskal-Wallis tests were used for comparisons as well. All statistical analyses
      were performed using SPSS version 11.5, Matlab version 7.2, Statistica version
      6.0 and S_PLUS 2000. The significance level was considered 5% (alpha = 0.05). The
      three methods used showed no significance difference in base survival
      probabilities. Overall, there was no significant difference among the survival
      probabilities or the trend of changes in survival probabilities calculated with
      the three methods, but the 4 year (48th month) and 4.5 year (54th month) survival
      rates were significantly different with Cox compared to standard and estimated
      probabilities in the neural network (p < 0.05). Kaplan-Meier and Cox showed
      almost similar results for the baseline survival probabilities, but results with
      the neural network were different: higher probabilities up to the 4th year, then
      comparable with the other two methods. Estimates from Cox proportional hazards
      and the neural network with three nodes in hidden layer were compared with the
      estimate from the Kaplan-Meier estimator as the gold standard. Neither comparison
      showed statistically significant differences. The standard error ratio of the two
      estimate groups by Cox and the neural network to Kaplan-Meier were no significant
      differences, it indicated that the neural network was more accurate. Although we
      do not suggest neural network methods to estimate the baseline survival
      probability, it seems these models is more accurately estimated as compared with
      the Cox proportional hazards, especially with today's advanced computer sciences
      that allow complex calculations. These methods are preferable because they lack
      the limitations of conventional models and obviate the need for unnecessary
      assumptions including those related to the proportionality of hazards and
      linearity.

PMID- 18819545
TI  - Detection and frequency of Stx2 gene in Escherichia coli O157 and O157:H7 strains
      isolated from sheep carcasses in Shiraz-Iran.
AB  - Enterohaemorrhagic Escherichia coli constitute a subset of serotypes (E. coli
      O157 and some other serogroups) of Shiga toxin-producing E. coli firmly
      associated with severe human illnesses like bloody diarrhoea and haemolytic
      uraemic syndrome. Escherichia coli O157:H7 is a zoonotic pathogen. They rarely
      cause disease in animals, live in the intestines of healthy sheep and ruminants
      are recognized as their main natural reservoir, so they can contaminate meat
      during slaughtering practices. The purpose of this study was epidemiological
      survey on the occurrence of E. coli O157:H7 in healthy sheep in Shiraz-Iran.
      Polymerase Chain Reaction (PCR) assay was developed to detect the Stx2 gene the
      only bacterial factor that has been associated with more severe disease. During a
      period of 7 months (December 2005 to June 2006), 153 slaughtered sheep at Shiraz
      slaughterhouse, were randomly selected and examined for surface carriage of E.
      coli O157:H7 by conventional plating and Stx2 gene detection by PCR technique. E.
      coli O157:H7 was found in 6(3.92%) of 153 sheep. The bacteria were isolated from
      5(3.34%) of 114 and 1(2.63%) of 38 sheep two or under two and more than 2 years
      old, respectively (p = 0.5). The contamination rate might vary depending on
      season, age and infection time. The higher frequency for younger animals may be
      due to differences in the composition of the gastrointestinal flora resulting
      from differences in diet. This is the first report of the presence of E. coli
      O157:H7 in sheep from Iran.

PMID- 18819546
TI  - Effect of N. sativa oil on impaired glucose tolerance and insulin insensitivity
      induced by high-fat-diet and turpentine-induced trauma.
AB  - The aim of this study was to investigate the effect of N. sativa oil on impaired
      glucose tolerance and insulin insensitivity induced by high-fat diet and trauma.
      Three dietary groups were used in this study; Rat-Chow (RC), N. sativa oil diet
      (Combination 4% N. sativa oil and 16% butter oil) (NSOD) and 20% Butter Oil Diet
      (BOD). Each group was subdivided in two groups; control and trauma. Diets were
      supplemented for five consecutive weeks body weight increase per week was
      calculated. At end of the dietary treatments, single dose (2 mL kg(-1) body
      weight) of turpentine was injected in the dorso-lumber region. Intravenous
      glucose tolerance test (i.v. GTT) was performed, insulinogenic index and insulin
      sensitivity was measured. The results showed butter oil diet significantly
      increased the body weights and visceral fats compared other two groups,
      respectively. Fasting glucose levels did not change in trauma induced rats while
      insulin levels increased significantly and it found highest in butter oil diet
      fed animals. Impaired glucose tolerance was found sever in BOD fed traumatized
      rats. N. sativa oil diet protected impaired glucose tolerance and insulin
      insensitivity induced either via saturated fatty acids or injury. In conclusion,
      N. sativa oil may be used in post surgery diabetic patients to prevent the long
      going adverse effects from surgical trauma.

PMID- 18819547
TI  - Production and characterization of a mesophilic lipase isolated from Bacillus
      stearothermophilus AB-1.
AB  - Using Bacillus stearothermophilus AB-1 isolated from air, the production of
      lipase was attempted along with its purification and characterization studies.
      When different carbon and nitrogen sources were supplemented in the culture
      medium, xylose, tryptophan, alanine, phenylalanine and potassium nitrate were
      found to be the best. During cultivation, the strain secreted most of its lipase
      content after 48 h. In particular, the lipase produced in the culture broth
      showed 300 U mL(-1) when cultivated at optimal temperature and pH of 35 degrees C
      and 7.5, respectively. The enzyme was purified using 60% ammonium sulfate
      precipitation and sephadex G200 column chromatography. The enzyme was stable up
      to 40 degrees C and in the range of pH 7-8. This research reports for the first
      time the characterization of mesophilic lipase from Bacillus stearothermophilus
      AB-1 isolated from air.

PMID- 18819548
TI  - An evaluation on intensity of infection of Pseudocercospora leaf spot disease of
      cowpea cultivars (Vigna unguiculata L. Walp), with respect to infector rows,
      dates of inoculation and cultivars, grown under field conditions in Northeast
      Thailand.
AB  - This investigation was carried out at the Experimental Farm, Faculty of
      Agriculture, Khon Kaen University, Khon Kaen, Thailand to evaluate intensity of
      infection of Pseudocercospora Leaf Spot disease of cowpea cultivars, grown under
      field conditions with the use of Yasothon soil series (Oxic Paleustults). The
      experimental design used was a strip split plot design with four replications.
      The experiment consisted of three factors, i.e., with and without infector rows
      (Factor A), with and without inoculation and inoculated dates, i.e. none
      inoculation, inoculated at days 15 and 30 after sowing of seeds in main plots
      (Factor B) and three cowpea cultivars of KVC7, KKU25 and IT81D-1228-14-1 (Factor
      C). The results showed that the use of infector rows of cowpea plants (KKU25)
      being sown at 15 days before sowing seeds of cowpea cultivars in main plots gave
      a similar intensity of disease as those infector rows being sown at 30 days
      before sowing seeds of cowpea cultivars in main plots but significantly higher
      than without infector rows. Pathogenic disease being inoculated to the cowpea
      plants at 15 days after the sowing of seeds in main plots gave significantly
      higher intensity of disease than none inoculation. The establishment of infector
      rows at 15 days ahead of the sowing of seeds in main plots together with an
      inoculation of the disease at 15 days after the sowing of seeds in main plots
      gave the best results in evaluating amount of the infected disease. Thus infector
      rows surrounded the main plots are required whenever trials on disease evaluation
      are taken place.

PMID- 18819549
TI  - Pre-treatment effect of different doses of soy isoflavones on spatial learning
      and memory in an ovariectomized animal model of Alzheimer's disease.
AB  - The aim of this study was to evaluate the effects of different doses of dietary
      soy meals (with or without isoflavone) on dementia in ovariectomized (OVX) animal
      model of Alzheimer's disease. Female Wistar's rats with the exception of intact
      group were ovariectomized at the first line of study. Animals were divided into 2
      main groups: control (c) and pre-treatment groups. Animals in pre-treatment
      groups received one of five types of diet during four weeks prior Nucleus Basalis
      Magnocellularis (NBM) electrical lesion normal diet (0), 10 g soy with isoflavone
      (10), 20 g soy with isoflavone (20), 10 g soy without isoflavone (-10) and 20 g
      soy without isoflavone (-20) in 30 g daily diet. The spatial learning and memory
      were tested using Morris water maze after electrical lesion. Rats were trained in
      water maze to find a hidden escape Platform. Rats received 6 blocks that each
      block consisted of 3 trials. Following acquisition trials, one probe trial was
      conducted in which the platform was removed. Soy meal diet (with or without
      isoflavone) in ovariectomized rats with Alzheimer's disease caused improvement of
      performance across 18 trials of Acquisition. Our results suggest that soy meal is
      a potential alternative to estrogen in the prevention and treatment of
      Alzheimer's disease.

PMID- 18819550
TI  - Assessment of NK cells response to hepatocyte derived chemotactic agents.
AB  - This project was aimed to examine the NK92 cells response as the CXC chemokine
      responder cells in rat model of liver disorder and injuries. Hepatocytes were
      isolated from Sprague-dawly rats and cultured on collagen type 1. Migration of
      NK92 cells was assessed using a 48 well micro-chemotaxis technique. Transwell
      chambers were positioned faced up, blocked Medium supernatant (500 microL)
      obtained from hepatocytes cultures were placed into the lower compartment of each
      Transwell. The upper compartment was filled with either 500 microL of NK92 cells.
      After washing, Membrane-attached cells were fixed; stained and Membrane-attached
      cells were counted by light microscopy and/or by size gating (9-14 microm) with
      an automated counter system. Human NK92 cells were attracted to recombinant human
      IP-10 in a concentration and time-dependent manner. NK92 cells also exhibited a
      chemotactic response to medium harvested from primary hepatocyte cultures.
      Isolated and cultured hepatocytes express several different chemokines. Although
      we identified that medium from hepatocyte cultures contains specific chemokines
      by immunoblotting, there is potential that migration assays detected yet other
      chemokines and other factors such as complement components. In this report, we
      demonstrated that hepatocytes expressed factors that were chemoattractive for
      human NK92 cells and that the factors must interact with the repertoire of
      receptors responsible for recruitment of these cells.

PMID- 18819551
TI  - Effect of Prunus avium roots on river bank strong.
AB  - A pulling effect by side roots is one way in which roots help to side in-plane
      strong of a little depth soil mass. In contrast to the effect of vertically
      enlarge roots, whereby soil is strengthened by an increase in its shear strength,
      the pulling effect strengthens the soil by increasing the tensile strength of the
      rooted soil zone. To verify whether or not a pulling effect exists in the root
      system of Prunus avium in the Roudsar, North Iran and to study the importance and
      size of this effect, a direct in situ test was led at a site in the Chaboksar
      Forests. The results from the site showed that, in the surface soil (0-30 cm),
      Side roots can provide a pull force of up to 490-712 N (Newtons) over a vertical
      cross-section area of 20-50 cm2, or an enhance in the pulling stability of the
      rooted soil by about 48.1%. The test results suggest that, together with the
      Prunus avium vertical roots, which keep the little depth rooted soil zone to the
      deep and more stable soil mass, the side roots of the Prunus avium, with their
      pulling effect, are able to make less against little depth instability in the
      forest slopes, such as little depth slide, to a certain degree.

PMID- 18819552
TI  - The effect of type of marginal land use on the production of biomass and plant
      diversity.
AB  - The objective of this study closely focuses on the settlement of the effect of
      marginal land use on plant diversity. The location of this study was Sar Firouze
      Abad region with rainfall of over 350 mm and slope of over 12%. Five treatments
      in terms of land use (exclusion area, grazed range, fallow, annual medic
      cultivation, wheat cultivation) done with the repetition of five times. The
      factors, such as the number of species, the number of plant bases in each
      species, the percentage of plant cover and biomass in each sampling were
      measured. The method used here is based upon complete randomized design applying
      Duncan test and Raunkiaer method for classification of plant species and also
      Shannon's diversity index of diversity and homogeny utilized. The results show
      that there are 76 species belonging to 60 genus and 19 families spreading in the
      region under study. The most dominant families are Fabaceae with 15 species
      covering 20% and Poaceae with 13 species covering 17%, respectively. According to
      Raunkiaer method the life form of the region species can be classified as
      Therophytes 66%, Geophytes 3%, Hemicryptophytes 26% and Chamaephytes 5%. The
      results also illustrate that the treatment of exclusion area has the most plant
      diversity, the percentage of plant cover and biomass in comparison with the rest
      of treatment cultivation and range grazed.

PMID- 18819553
TI  - Effect of microbial inoculants on the nutritive value of corn silage for beef
      cattle.
AB  - This study investigated the effect of a new microbial inoculant product on the
      composition and nutritive value of corn silage in big silo over one year that
      used beef cattle. Six Holstein beef steer (BW = 225 +/- 17) were allotted to 2 x
      2 repeated Latin square design at two 21 days periods (adaptation, 14 days and
      sample collection, 7 days) for evaluation the effect of microbial inoculation on
      the composition and nutritive value of corn silage for beef cattle. Two
      treatments, forages were untreated or treated at ensiling with Lactobacillus
      plantarum and Propionibacterium acidipropionici silage inoculants. After 45 days
      from ensiling, the ration that contained 94.5 and 5, 0.2, 0.2, 0.1% of DM silage
      and ground barely, mineral-vitamin, dicalcium phosphate, salt, respectively, were
      offered for free choice consumption. Treatment with Lactobacillus plantarum and
      Propionibacterium acidipropionici inoculant increased daily dry matter intake and
      subsequently NDF, ether extract, crude protein and ash. Apparent digestibility of
      DM and nutrients were significantly increased by microbial inoculation. Microbial
      inoculation can improve the nutritive value of corn silage for beef cattle.

PMID- 18819554
TI  - Mercury release from dental amalgam restorations after magnetic resonance imaging
      and following mobile phone use.
AB  - In the 1st phase of this study, thirty patients were investigated. Five
      milliliter stimulated saliva was collected just before and after MRI. The
      magnetic flux density was 0.23 T and the duration of exposure of patients to
      magnetic field was 30 minutes. In the 2nd phase, fourteen female healthy
      University students who had not used mobile phones before the study and did not
      have any previous amalgam restorations were investigated. Dental amalgam
      restoration was performed for all 14 students. Their urine samples were collected
      before amalgam restoration and at days 1, 2, 3 and 4 after restoration. The mean
      +/- SD saliva Hg concentrations of the patients before and after MRI were 8.6 +/-
      3.0 and 11.3 +/- 5.3 microg L(-1), respectively (p < 0.01). A statistical
      significant (p < 0.05) higher concentration was observed in the students used
      mobile phone. The mean +/- SE urinary Hg concentrations of the students who used
      mobile phones were 2.43 +/- 0.25, 2.71 +/- 0.27, 3.79 +/- 0.25, 4.8 +/- 0.27 and
      4.5 +/- 0.32 microg L(-1) before the amalgam restoration and at days 1, 2, 3 and
      4, respectively. Whereas the respective Hg concentrations in the controls, were
      2.07 +/- 0.22, 2.34 +/- 0.30, 2.51 +/- 0.25, 2.66 +/- 0.24 and 2.76 +/- 0.32
      microg L(-1). It appears that MRI and microwave radiation emitted from mobile
      phones significantly release mercury from dental amalgam restoration. Further
      research is needed to clarify whether other common sources of electromagnetic
      field exposure may cause alterations in dental amalgam and accelerate the release
      of mercury.

PMID- 18819555
TI  - In vitro study on regeneration of Gladiolus grandiflorus corm calli as affected
      by plant growth regulators.
AB  - In this study, in vitro organogenesis of Gladiolus grandiflorus cultivar pink
      corm segments were evaluated by culturing corm calli in modified MS medium
      supplemented with 3% sucrose and 0.7% agar with different concentration of BAP
      (0, 1, 2 and 4 mg L(-1) medium) and NAA (0, 0.5, 1 and 2 mg L(-1) medium) in
      factorial experiment of Completely Randomized Design (CRD). In order to obtain
      Gladiolus calli, corm segments (Aprox. 5 x 5 x 1 mm in size) were kept in
      modified MS medium (Murashige and Skoog, 1962) that was supplemented with 1 mg L(
      1) 2, 4-D, 3% sucrose and 0.7% agar. The results showed that increasing the
      concentration of BAP from 0 to 2 mg L(-1) medium simulated plantlet regeneration
      but no significantly effect was obtained on shoot and cormel organogenesis
      between 2 and 4 mg L(-1) BAP concentration in medium. Increasing of NAA content
      in media without BAP developed rootlet significantly. Interaction results showed
      that increasing BAP content against decreasing of NAA concentration stimulates
      the shoot and cormel proliferation.

PMID- 18819556
TI  - The effect of levamisole on sheep trachea alone and with trichlorfon combination.
AB  - The aim of this study is to determine the effect of levamisole and levamisole
      trichlorfon combination on isolated sheep trachea. Contraction was achieved with
      levamisole concentrations (10(-8)-10(-3) M) on tracheal strips of adult sheep (>
      1 year of age). Pretreatment with trichlorfon (10(-7) M)-levamisole (10(-7) M)
      decreased the pD2 and E(max) of Ach when compared to levamisole pretreatment (p <
      or = 0.01). Pretreatment with levamisole (10(-7) M), decreased the E(max) (p < or
      = 0.01) and pD2 (p < 0.05) of bethanechol concentrations (10(-8)-10(-3) M)
      significantly. Pretreatment with atropine (10(-6) M) decreased the E(max) of
      levamisole (10(-4) M) significantly (p < 0.05). To conclude, levamisole acted
      mainly on the muscarinic receptors of the sheep trachea and this effect was
      partly inhibited by atropine. Adverse interaction was present between levamisole
      and trichlorfon.

PMID- 18819557
TI  - Evaluation of seed yield-related characters in sesame (Sesamum indicum L.) using
      factor and path analysis.
AB  - Fifteen sesame genotypes were grown in a randomized complete block design with 3
      replications during 2004, in experimental station of Agricultural College, Shiraz
      University in Badjgah, Iran. Many plant traits were scored in the field. Path
      coefficient analysis and factor analysis divided the 15 measured variables into 5
      factors. The 5 factors explained 81% of the total genetic variation in the
      dependence structure. Factor 1 was strongly associated with number of capsules in
      the main stem, length of floral axis, number of capsules per plant and plant
      height. Other factors (2, 3, 4 and 5) explained the rest of genetic variations
      and may not be important in sesame breeding programs.

PMID- 18819558
TI  - Ultrastructural changes in shoot apical meristem of canola (Brassica napus cv.
      Symbol) treated with sodium chloride.
AB  - In the present research, structure and ultrastructure of shoot apical meristem of
      canola (Brassica napus cv. Symbol) under salinity conditions were investigated.
      The experiments were conducted in five groups (0, 3, 6, 9, 12 dS m(-1)) under
      greenhouse conditions. Sampling of apical meristem and TEM tissue preparation
      procedure were carried out. Semithin and ultrathin sections were prepared and
      viewed in light and electron microscopy, respectively. The results included
      reduction of meristem size, disorders in meristem structure. Also formation of
      autophagic vacuoles was observed that is probably one of the plant responses to
      salt stress for more water storage in these vacuoles and decreasing of cell water
      requirements.

PMID- 18819559
TI  - Effects of gamma irradiation on ruminal DM and NDF degradation kinetics of
      alfalfa hay.
AB  - The effects of gamma irradiation on ruminal dry matter, Neutral Detergent Fiber
      (NDF) degradation of alfalfa hay were investigated. Alfalfa hay samples were
      irradiated by gamma irradiator at doses of 50, 100 and 150 kGy under identical
      conditions of temperature and humidity. Nylon bags of untreated or irradiated
      samples were suspended in the rumen of three Taleshi bulls for up to 96 h and
      resulting data were fitted to non-linear degradation model to calculate
      degradation parameters. Results indicated that the washout fractions of dry
      matter and NDF increased linearly (p < 0.001) with increasing irradiation dose.
      The b fraction and the degradation rate of the b fraction (c) of DM and NDF were
      the highest at 50 kGy dose. Effective degradability of DM and NDF increased
      linearly with increasing irradiation dose. Gamma irradiation at doses of 50, 100
      and 150 kGy increased the effective NDF degradability of alfalfa hay at rumen
      outflow rate of 0.05 h(-1) by about 8, 11 and 12%, respectively. Gamma
      irradiation affects on the hydrogenic bonds and with theirs breakdowning causes
      the wander-valls power weaken, that results in the degradation of cellulose and
      increasing of DM and NDF degradability.

PMID- 18819560
TI  - Hypolipidaemic effects of Ballota undulata in rabbits.
AB  - The aim of to study the effect of Ballota undulata (70% EtOH) extract on lipid
      profile on Rabbits. The plant extract was orally administered to the atherogenic
      rabbits (atherogenic diet + cholesterol powder supplement 400 mg/kg/body
      weight/day dissolved in 5 mL coconut oil) at dose of 1.2 g kg(-1) body
      weight/day. During the overall period of the experiment blood was collected and
      serum was analyzed for lipid profile. Animals were sacrificed; the heart and the
      liver were collected and kept at -20 degrees C until assayed. Biochemical
      analysis of blood serum and tissue (liver and heart muscle) level were made for
      cholesterol, phospholipids and triglycerides. In addition blood serum was
      analyzed further for HDL-Cholesterol. All the results were statistically analyzed
      using students t-test. Hypolipidaemic nature of Ballota undulata (70% EtOH)
      extract was studied in hyperlipidaemic Rabbits. The increased cholesterol levels
      were brought to normal by administration of Ballota undulata. Serum cholesterol
      levels dropped from 940.7 to 230.41 (75.55%) and further to 119.2 (87.32%) by the
      end of the experiment. Similarly, phospholipids and triglycerides levels were
      observed to be also reduced. The tissues lipids profiles of liver and heart
      muscle showed similar changes in those noticed in serum lipids. Ballota undulata
      possesses active hypolipidaemic constituents.

PMID- 18819561
TI  - A new variety of Salvia macrosiphon (Lamiaceae) for Iran.
AB  - In this study, Salvia macrosiphon Boiss. var. longiflora Kharaz. is reported for
      the first time as one of the new varieties of Salvia macrosiphon in Iran. The
      morphological characters of this variety have been described in details.

PMID- 18819562
TI  - A 64 years old man with multiple myeloma and low HDL.
AB  - In a 64 year old man with dyspnea and palpitation and fatigue and non angina
      chest pain, we found all the Para clinics prefect but only it showed low HDL and
      a normocytic, normochromic anemia. In searching about cause of anemia, in bone
      marrow biopsy showed Paraproteinemia. Therefore false low HDL because of
      paraproteinemia, leads to miss-diagnosis of cardiovascular disease.

PMID- 18819563
TI  - Investigation fauna and density of population of spiders in the desert and
      pomegranate orchards in Tehran and Semnan provinces.
AB  - The present study was carried out to consideration the spider's fauna and
      abundance of spiders in the desert and pomegranate orchards in Tehran and Semnan
      provinces, during 2007. Specimens were collected from desert and pomegranate
      orchards by pitfall trap, shaking tree, pans, bottle and aspirator and were taken
      to the laboratory after labeling. A total of 1231 specimens were classified in 45
      species and 36 genera belonged to 17 families. Among them 4 spider species were
      new for Iranian spider fauna. The families Lycosidae, Linyphiidae, Gnaphosidae
      and Theridiidae had height population in the study areas. Specimens were immature
      in the winter and spring and they were adult in the summer. The dominant species
      in all of study regions was Pardosa agrestis (Westring).

PMID- 18819564
TI  - The effects of electromagnetic field on the microstructure of seminal vesicles in
      rat: a light and transmission electron microscope study.
AB  - In the industrial world, almost everyone is unavoidably exposed to ambient
      electromagnetic field (EMF) generated from various technical and household
      appliances. Controversy exists about the effects of EMF on various tissues of the
      living bodies. Seminal vesicles as one of these accessory glands play an
      important role in natural seminal fluid formation and the effects of EMF on its
      tissue is worthy of investigation. In order to examine this 30 rat were selected
      and kept for one weeks in quarantine and 15 (experimental group) were exposed to
      50 Hz (non-ionizing radiation) during postnatal life for 2 months. The materials
      were processed and observed under a light and transmission electron microscope.
      In the experimental rats epithelial and basal cells showed significant
      destructions presented by heterochromatin and dense nuclei. Cell debris and
      abnormal areas was recognizable in the stromal connective tissue. Obvious
      vacuolization was present within the epithelial cell cytoplasm and also between
      the cellular organelles. The nuclei of the endothelial cells of the blood vessels
      were more rigid and endothelial cell cytoplasm contained a lot of vacuoles and
      pinoctotic vesicles. The results suggested that EMF exposure may cause profound
      changes in the vesicle seminal tissues. Therefore exposure to EMF may result in
      pathological changes that lead to sub fertility and infertility.

PMID- 18819565
TI  - The scaling technique in Palmer Drought Severity Index; generalized calibration
      and modification.
AB  - The scaling technique in calculating Palmer Drought Severity Index (PDSI) has
      specific properties, which is considered in details, in this study. The Palmer
      scaling method contains a physically-based weighting factor called climatic
      characteristic coefficient, K. This factor, is the ratio of average moisture
      demand to average supply in a regional water balance, whose related coefficients
      and involved equation parameters should be calibrated according to any special
      case study. Therefore, in this study, the generalizing procedure of obtaining K
      value with no dependency on particular area, in addition to some modifications in
      the process was analytically developed. The generalized procedure has an
      appropriate potential for various purposes such as; correctly identifying
      analytical K-formula, simplifying its application, recognizing its limitations
      and moreover it can be used in other researches for developing its advantages.
      The proposed procedure and its modifications also applied for a case study (e.g.,
      Maharlue catchment, Fars province, Iran). The outputs of the application
      validated the suggested modifications; therefore, the obtained K-values can be
      used for other studies in the region.

PMID- 18819566
TI  - Estimation of water turbidity in Gorgan Bay, South-east of Caspian Sea by using
      IRS-LISS-III images.
AB  - In this research, usefulness of IRS-LISS-III data of Gorgan Bay, South-east of
      Caspian Sea located in North of Iran for water turbidity mapping, has been
      tested. After correction of geometric and radiometric errors, the resulting
      radiance data were used for examination of correlations between the remotely
      sensed and in situ water turbidity data simultaneously measured by the Secchi
      depth approach. Results of this research showed good relations between the Secchi
      depth and spectral data. The fitted statistical model was very significant (R2 =
      0.77) and test of the model performance by independent samples was encouraging.
      Because of the low costs encountered with acquisition and processing of remotely
      sensed data, further research in larger scales for the purpose of more precise
      test of the approach for water turbidity mapping and monitoring is recommended.

PMID- 18819567
TI  - Foraging behaviour of the african honey bee (Apis mellifera adansonii) on Annona
      senegalensis, Croton macrostachyus, Psorospermum febrifugum and Syzygium
      guineense var. guineense flowers at Ngaoundere (Cameroon).
AB  - To determine the apicultural value of Annona senegalensis Pers. 1806
      (Annonaceae), Croton macrostachyus Hochst. Ex Del. 1847 (Euphorbiaceae),
      Psorospermum febrifugum Spach 1836 (Hypericaceae) and Syzygium guineense (Will.)
      DC var. guineense 1828 (Myrtaceae), Apis mellifera adansonii Latreille 1804
      (Hymenoptera: Apidae) activity was observed on their flowers in the area of
      Ngaoundere, from January to May, in 2002 and 2003. Flowers of each plant species
      were prospected at least four days per month, between 7 am and 6 pm, for the
      registration of the nectar and/or pollen foraging behaviour of A. m. adansonii
      workers. Results show that A. m. adansonii harvested nectar and pollen of each
      plant species. The greatest number of workers foraging simultaneously on a plant
      varied from 9 in P. febrifugum to 3600 in S. g. guineense. A. m. adansonii
      workers were faithful to each plant species. A. senegalensis, C. macrostachyus,
      P. febrifugum and S. g. guineense could be cultivated and protected to increase
      honey production. A. senegalensis could enable beekeepers to increase their
      pollen production as a hive product. During foraging, A. m. adansonii workers
      increased pollination possibilities of each plant species.

PMID- 18819568
TI  - In vitro regeneration of Irvingia gabonensis by somatic embryogenesis.
AB  - A productive genotype of Irvingia gabonensis were cultured in vitro for induction
      embryogenic calli, somatic embryogenesis and regeneration of plantlets. Fragments
      of young leaves were used as primary explants. Callogenesis was initiated by
      culture of explants during 30 days on Murashige and Skoog medium half strength
      (MS/2) supplemented with 1-6 mg L(-1) of 2,4-dichlorophenoxyacetic acid (2,4-D).
      The highest percentage of explants forming calli is 85.1% at 3 mg L(-1) of 2,4-D.
      Somatic embryos were obtained after a subculture of embryogenic calli during 60
      days on MS/2 supplemented with 1-3 mg L(-1) of BAP. The highest percentage of
      embryogenic calli which differentiates somatic embryos is 63.8 +/- 2.3% at 1 mg
      L(-1) of 6-benzylaminopurine (BAP). The highest number of somatic embryos per
      callus which is 43.6 is obtained with 2 mg L(-1) of this phytohormone. When
      isolated from calli and sub-cultured during 30 days on MS/2 supplemented with 2
      mg L(-1) of BAP, somatic embryos germinate with a highest percentage of 83%. The
      subculture of germinated somatic embryos on the same Basal Medium (BM)
      supplemented with 4 mg L(-1) of BAP and 2 mg L(-1) of Naphthalene Acetic Acid
      (NAA) during 80 days gives rise to the plantlets with 82.7 +/- 4.8% of success.
      With this combination, each plantlet has average length of 5.6 cm, bears 3.3
      leaves and 7.2 roots with 1 or 2 pivoting roots. Plantlets acclimatized on a
      mixture sterilized soil/vermiculite at equal volume survive at 93%. Results of
      this study constitute a new way for a production of Irvingia gabonensis seedlings
      with pivoting root and they permit to arrest the difficulties of natural and
      horticultural reproduction.

PMID- 18819569
TI  - Age and sex related variations in protein and carbohydrate levels of Galleria
      mellonella (Linnaeus, 1758) (Lepidoptera: Pyralidae) in constant lightness and
      darkness.
AB  - Variations in protein and carbohydrate levels correlated with the age and sex of
      Galleria mellonella (Linnaeus, 1758) (Lepidoptera: Pyralidae) in constant
      lightness and darkness were investigated. Tests were conducted under laboratory
      conditions at 28 +/- 2 degrees C temperature and 65 +/- 5% relative humidity.
      Insects were fed on combs without honey. Protein level in 100 mg of adults
      increased in the first days of adult life of females in connection with their age
      and then decreased. No difference was observed in males. Carbohydrate level in
      100 mg of adults increased in both sexes in connection with their age. In all
      tests carbohydrate and protein levels of females were found higher than males.
      Protein and carbohydrate levels of adult G. mellonella varied in connection with
      the photoperiod regimes implemented. Decrease in the nutrient levels was observed
      in constant darkness.

PMID- 18819570
TI  - Isolation and identification of a lipase producing Bacillus sp. from soil.
AB  - Lipase production in an indigenous lipolytic Bacillus sp. was detected in media
      containing Tributyrin-Tween 80 and Rhodamine B-Olive oil. The statistical Taguchi
      model was used to predict the optimum experimental conditions for bacterial
      growth and lipase production. Partial optimization was carried out for selection
      of salt base, oil, glucose, NH4Cl and yeast extract concentrations, inoculum
      density, pH and agitation. Maximum lipase activity was detected in the cell free
      supernatants of cultures grown in a medium containing 10 g L(-1) yeast extract,
      15 g L(-1) NH4Cl, 3 g L(-1) K2HPO4, 1 g L(-1) KH2PO4, 0.1 g L(-1) MgSO4 x 7H2O, 2
      g L(-1) glucose, 0.6 mM MgCl2 and 15 ml L(-1) olive oil, pH 8.5 at 30 degrees C
      for 24 h and low agitation. The amount oflipase produced in the designed medium
      was in agreement with the predicted values by the statistical method. 16S rRNA
      cloning and sequencing identified the test organism as Bacillus pumilus.

PMID- 18819571
TI  - The effect of Rosa damascena essential oil on the amygdala electrical kindling
      seizures in rat.
AB  - We investigated the effect of Rosa damascena Mill, essential oil on the
      development of induced amygdala kindling seizures. Male Wistar rats were
      implanted with one tripolar and two monopolar electrodes in right basolateral
      amygdala and dura surface, respectively. The control group was injected solvent
      of essential oil and two experimental groups were injected 750 and 1000 mg kg(-1)
      of essential oil (ip), 30 min before a daily kindling stimulation. The number of
      stimulations required for the first appearance of seizure stages was
      significantly larger in two experimental groups than in control group. Mean after
      discharge duration was significantly different and essential oil reduced the
      increase of after discharge duration. Mean after discharge amplitude was also
      shorter in the groups treated with essential oil than in control group. Duration
      time for 5th stage of seizure at fully-kindled rats was significantly shorter in
      two experimental groups than control group. These results suggest that Rosa
      damascena essential oil significantly retarded the development of seizure stages
      and possesses the ability to counteract kindling acquisition. The flavonoids of
      Rosa damascena may act via GABAA receptors as previous studies have proposed for
      flavonoids of other medicinal plants. More detailed studies are recommended to
      define the effective component(s) of Rosa on different types of epilepsy.

PMID- 18819572
TI  - Application of two way indicator species analysis in lowland plant types
      classification.
AB  - A TWINSPAN classification of 60 sample plots from the Khanikan forest (North of
      Iran) is presented. Plant types were determined from field observations and
      sample plot data arranged and analyzed in association tables. The types were
      defined on the basis of species patterns of presence, absence and coverage
      values. Vegetation was sampled with randomized-systematic method. Vegetation data
      including density and cover percentage were estimated quantitatively within each
      quadrate and using the two-way indicator species analysis. The objectives of the
      study were to plant type's classification for Khanikan lowland forest in North of
      Iran, Identification of indicator species in plant types and increase our
      understanding in regarding to one of Multivariate analysis methods (TWINSPAN).
      Five plant types were produced for the study area by TWINSPAN, i.e., Menta
      aquatica, Oplismenus undulatifolius, Carex grioletia, Viola odarata and Rubus
      caesius. Therefore, at each step of the process, the program identifies indicator
      species that show strongly differential distributions between groups and so can
      severe to distinguish the groups. The final result, incorporating elements of
      classification can provide a compact and powerful summary of pattern in the data
      set.

PMID- 18819573
TI  - The study of seed yield and seed yield components of lentil (Lens culinaris
      Medik) under normal and drought stress conditions.
AB  - In this study yield and seed yield components of twenty lentil (Lens culinaris
      Medik) genotypes were compared in a split plot RCBD based design with 3
      replications at the Zanjan University Research Farmland in 2004. The main plots
      were lentil planted under drought stress and non stress (irrigation) condition
      and subplots were twenty of genotype lentil. There were significant differences
      between traits in lentil genotypes. The seed yield per plant was sensitive to
      drought stress but 100 seed weight was more tolerance and stable trait in drought
      condition. As correlation analysis of traits in various stress condition, the
      harvest index, seed yield per plant, pods per plant and biological yield were
      correlated with grain yield. In addition harvest index, seed yield per plant,
      pods/plant and biological yield were the most important traits that have a
      relationship with grain yield.

PMID- 18819574
TI  - Sequence analysis of GDSL lipase gene family in Arabidopsis thaliana.
AB  - To analyze sequence characters of GDSL lipase gene family in Arabidopsis
      thaliana, 108 members of GDSL lipases were analyzed using data mining. The gene
      structures display remarkable diversity, consisting of zero to 13 introns. And
      the genes are asymmetrically distributed in chromosome 1-5, some of which are
      arranged in tandem. Phylogenetically, they were classified into three groups.
      Lipase-GDSL domain (PF00478) is housed at or close to N-terminus, or in the
      middle of amino acid sequences, additionally in which other domains and
      replicates were also found. Most GDSL lipases contain a signal peptide for
      conducting the secretary pathway. They are predicted to be extracellularly
      secreted, or target to mitochondria, chloroplast or any other parts of the cells.
      Functionally, these lipases are potentially involved in multiple physiological
      roles including seed germination, flowering and defense reactions. This study
      will help further understand the sequences and functions of Arabidopsis GDSL
      lipases.

PMID- 18819575
TI  - Rutin from different parts of Capparis spinosa growing wild in Khuzestan/Iran.
AB  - A qualitative and quantitative analysis of rutin from leaves, fruits and flowers
      of Capparis spinosa growing wild in Khuzestan was achieved. After soxhelet
      extraction of fats in diethyl ether, rutin was extracted by maceration using 50%
      EtOH. The ethanol extracts of these parts were separated by preparative TLC on
      silica gel precoated plate with a mixture of butanol: acetic acid (4:1, by
      volume) as the developing solvent. The spots were visualized under ultraviolet
      light (254 nm). Rutin was qualified by comparison of its R(f) value with that of
      standard. UV/Vis spectrum of separated rutin was also compared with those of
      standards and showed characteristic wavelengths at 260 and 360 nm. Purified rutin
      was quantified by UV/Vis spectrophotometric determination at 360 nm. The
      calibration curve was linear in the range of 0.156-2.5 microg mL(-1) with
      detection limit of 0.0731 microg mL(-1). The purity of extracted rutin from
      leave, flower and fruit determined by high performance liquid chromatography were
      90.41, 87.25 and 64.56%, respectively. The amounts of rutin in leaves, fruits and
      flowers were 61.09, 6.03 and 43.72 mg per 100 g of dried powder, respectively. By
      analyzing the spiked samples of leave, flower and fruit the recovery of the
      UV/Vis method was in the range of 102-107.6%.

PMID- 18819576
TI  - Critical period of weed control in winter canola (Brassica napus L.) in a semi
      arid region.
AB  - In order to determine the critical period of weed control in winter canola
      (Brassica napus L. cv. Okapi) an experiment was carried out at research field of
      Tarbiat Modarres University, Tehran, Iran on 2004-2005 growing season. Fourteen
      experimental treatments which divided into two sets were arranged in Randomized
      complete blocks design with four replications. In the first set, the crop was
      kept weed-free from emergence time to two-leaf stage (V2), four-leaf stage (V4),
      six-leaf stage (V6), eight-leaf stage (V8), early flowering (IF), 50% of silique
      set (50% SS) and final harvest (H). In the second set, weeds where permitted to
      grow with the crop until above mentioned stages. In this study critical period of
      weed control was determined according to evaluate seed bank emerged weed biomass
      effect on canola grain yield loss using Gompertz and logistic equations. Result
      showed a critical time of weed control about 25 days after emergence (between
      four to six-leaf stages) with 5% accepted yield loss. Therefore, weed control in
      this time could provide the best result and avoid yield loss and damage to
      agroecosystem.

PMID- 18819577
TI  - Plant regeneration from cell suspension culture of potato (Solanum tuberosum L.).
AB  - In the present study, for callus production leaf and stem segments of potato
      cultivar White Desiree were cultured on MS medium supplemented with 2,4-D, NAA
      and Kinetin (callus production medium). Calli then were transferred in the same
      liquid medium for cell suspension production. In the next step cell suspensions
      were transferred back to the callus production medium. Finally, calli derived
      from cell suspension were cultured on 6 different shoot initiation media (S1-S6).
      However, on S6 medium with combination of GA3 and BAP more than 80% of the calli
      produced shoot buds and shoots. Fully grown shoots then were rooted and produced
      whole plants. Chromosome and morphological analysis showed no somaclonal
      variation among regenerated plants.

PMID- 18819578
TI  - Insecticidal properties of Verbascum cheiranthifolium against R. dominica on
      wheat and barley.
AB  - Tissues of higher plants contain novel natural substances that can be used to
      develop environmental safe methods for insect control. In this study, ethanol
      extract from flowers of Verbascum cheiranthifolium Boiss. (Scrophulariaceae) was
      examined for their effect on mortality and progeny production against adults of
      Rhyzopertha dominica (F.) on two commodities, wheat and barley. The botanical
      extract was applied at five dose rates, which 0.25, 0.5, 1.0, 2.0 and 3% (w/v).
      Adults of R. dominica were exposed to the treated wheat and peeled barley at 25
      degrees C and 65% RH and mortality was assessed after 24 h, 48 h, 7 day, 14 day
      and 21 day of exposure. Then all adults were removed and the treated substrate
      remained at the same conditions for an additional 45 day after this interval, the
      commodities were checked for progeny production. In two commodities mortality
      increased with the increase of dose and exposure interval. Results indicated that
      on wheat, mortality was 100% after 14 days of exposure at the highest dose rate.
      Whereas, in the same conditions mortality of adults on barley was 63%. Thus plant
      extract was more effective against adults of R. dominica on wheat than
      application of barley. Interestingly in two diets, complete suppression (100%) of
      the progeny production was observed in the treated wheat and barley than in
      control even in the lowest dose rate.

PMID- 18819579
TI  - Population growth of the Tellinid bivalve tellina foliacea in the Hendijan Coast,
      Persian Gulf.
AB  - Length-frequency and growth of one of the dominant species, Tellina foliacea
      (Linnaeus, 1758) (Bivalve, Tellinidae) in the Hendijan coast, Khuzestan province
      (Persian Gulf) were studied from summer 2005 to spring 2006. Sampling was done
      seasonally with vanveen grab from 5 stations. Stations were located 0.5 mile
      apart and samples were collected from approximately 8 m depth. The population
      structure presented a size range between 0.5 and 6.5 mm length, being mainly
      formed by individuals 3 to 4 mm, that were dominant in winter. Recruitment rate
      was low and the major contribution of recruits was found in spring. Growth
      parameters of the Von Bertalanffy growth function were estimated to be L = 7.70
      mm, K = 1.200 y(-1), t0 = 0.9 y.

PMID- 18819580
TI  - Dietary patterns among pregnant women in the west-north of Iran.
AB  - This study was conducted to assess the food consumption pattern and nutrient
      intakes of pregnant women residing in Maku-the west north of Iran. In this cross
      sectional study, 284 pregnant women (142 from urban area and 142 from rural
      areas) participated. Subjects were interviewed privately, face-to-face. Dietary
      intake data was collected using two 24 h recalls and a food frequency
      questionnaire for 3 months. Mean consumption of grains and dairies was higher in
      rural women compared to their counterparts in urban areas. Women in urban areas
      consumed 140 g fruits compared to 248 g consumed by rural women. There were no
      significant differences regarding consumption of vegetables, pulses, fat and oils
      between these two groups. All women consumed adequate amount of energy, protein,
      thiamin and niacin (> 75% RDA). Intake of vitamin B6, folate, vitamins A and D,
      iron, phosphorus, calcium, magnesium and zinc was not sufficient in these women.
      Inadequate intake of vitamin C and riboflavin was also reported in urban women.
      Percentage of energy from carbohydrate, fat and protein was 66, 23 and 11% for
      urban women, respectively and 68, 20 and 12% for rural women, respectively. Iron
      intake was lower in urban women compared to rural women. The findings indicated
      that rural women have better nutritional status than urban women. Future studies
      should determine factors associated with food consumption pattern in these women.

PMID- 18819581
TI  - Quality evaluation of different honey samples produced in Peshawar valley.
AB  - The present study was designed to evaluate different honey samples obtained from
      local market for their quality parameters for assessment of their feasibility for
      foreign export by comparing it with international standards. The study was
      conducted at PCSIR laboratories complex, Peshawar, during 2006. The tested
      samples were evaluated for moisture content, Ash percentage, acid content, HMF
      and reducing sugars percentage. The moisture content of locally produced honey
      was in the range of 14.5 to 18.23%. The ash content of locally produced honey
      samples ranged between 0.047-0.35 which is within the standard limits. The acid
      content of the honey samples ranged between 19.5 and 38.0 meq kg(-1). The HMF
      contents of locally produced honeys ranged from 5.3 to 23.20 mg kg(-1). The
      content of reducing sugar of the tested samples ranged between 43.14 and 81.40%
      for the tested samples of locally produced honey. All of the samples were found
      to be in acceptable range of international standards for all of the tested
      parameters except for only one sample with lower reducing sugars. These samples
      were marked to be according to the international standards and are healthy for
      human consumption.

PMID- 18819582
TI  - Resistance to foliage feeding aphid in wheat.
AB  - Experimental trials were conducted at Integrated Pest Management Programme,
      National Agriculture Research Centre Islamabad, to evaluate the resistance of
      host plants (cereals) against Rhopalosiphum padi (L.). For evaluation of
      susceptibility, twenty varieties/-advanced lines of National Uniform Wheat Yield
      Trails (NUWYT) Normal (N) of year 2004-2005 were used. In seedling bulk tests
      varieties/advanced lines were grouped into three categories resistant, moderately
      resistant and susceptible. Data from seedling bulk tests showed that DN-47 and PR
      87 lines of wheat were resistant to aphid as compared to the other varieties/
      advanced lines. In antixenosis tests varieties/-advanced lines were grouped into
      three categories, least preferred, moderately preferred, highly preferred. Lines
      V-01180, DN-47 and PR-84 were least preferred, sixteen varieties/-advanced lines
      were moderately preferred and only one variety V-9021 was found to be highly
      preferred.

PMID- 18819583
TI  - Free radical scavenging activity of selected medicinal plants of Eastern
      Botswana.
AB  - Water and methanol extracts from roots of Ozoroa paniculosa (Anarcardiaceae);
      seeds of Colophospermum mopane (Caesalpiniaceae) and Cucumis metuliferus
      (Cucurbitaceae) ripe fruits were assessed for in vitro antioxidant activity. Free
      radical scavenging activity was measured spectrophotometrically as maximum fading
      power of DPPH at 525 nm. Water and methanol extracts of Ozoroa paniculosa
      exhibited higher scavenging potency than extracts of either Colophospermum mopane
      or Cucumis metuliferus at all tested concentrations. None of the extracts from
      Cucumis metuliferus exhibited any recognizable free radical scavenging activity.
      Above 50 microg mL(-1) both water and methanol extracts of Ozoroa paniculosa
      exhibited 91% scavenging activity similar to the control compounds L-ascorbic
      acid (91%) and (-) epicatechin (92%). Between 50-100 microg mL(-1), water and
      methanol extracts of Colophospermum mopane exhibited scavenging potency of < or =
      70%. However, above 100 microg mL(-1), both water and methanolic extracts of C.
      mopane exhibited scavenging activity > 70%. Chloroform extracts of all the tested
      plants showed poor scavenging activity (< 30%). The order of scavenging potency
      for the tested samples was as follows: L-ascorbic acid > or = epicatechin > O.
      paniculosa (methanolic extract) > O. paniculosa (water extract) > O. paniculosa
      (ethylacetate extract) > C. mopane (methanolic extract) > C. mopane (water
      extract) > all extracts of C. metuliferus. These findings lend credence to the
      use of these plants as anti-inflammatory and antioxidant agents in folk medicine.

PMID- 18819584
TI  - Mental disorder assessed by General Health Questionnaire and back pain among
      postmenopausal Iranian women.
AB  - The aim of this study was to investigate the association between mental disorder
      and back pain among postmenopausal Iranian women. Three thousand six hundred and
      fifty five postmenopausal women were interviewed in the second National Health
      Survey (2nd NHS) in the year 2000, in Iran. Of whom, 2953 women were included in
      this study. Back pain (BKP) was considered as dependent variable and mental
      disorder as independent variable. Factors like age, Body Mass Index (BMI),
      residential area, employment, literacy, smoking habit, marital status and spinal
      fractures were considered as confounders. Logistic regression models have been
      applied for data analysis. The BKP prevalence was 40.1% and the prevalence of
      mental disorder was 44.3%. After adjustment for confounders, mental disorder was
      positively associated with BKP, OR (CI): 1.615 (1.36, 1.91). This study confirmed
      that BKP and mental disorder are common problems and these two factors are
      associated amongst postmenopausal women. Further longitudinal studies are
      recommended to specify casual inferences.

PMID- 18819585
TI  - The effect of type of marginal land use on the plant diversity.
AB  - The objective of this study closely focuses on the settlement of the effect of
      marginal land use on plant diversity. The location of this study was Sar Firouze
      Abad region with rainfall of over 350 mm and slope of over 12%. Five treatments
      in terms of land use (exclusion area, grazed range, fallow, annual medic
      cultivation, wheat cultivation) done with the repetition of five times. The
      factors, such as the number of species and the number of plant bases in each
      species in each sampling were measured. The method used here is based upon
      complete randomized design applying Duncan test and Raunchier method for
      classification of plant species and also Shannon-Wiener index of diversity and
      homogeny utilized. The results show that there are 76 species belonging to 60
      genus and 19 families spreading in the region under study. The most dominant
      families are Fabaceae with 15 species covering 20% and Poaceae with 13 species
      covering 17%, respectively. According to Raunchier method the life form of the
      region species can be classified as Therophytes 66%, Geophytes 3%,
      Hemicryptophytes 26% and Chamaephytes 5%. The results also illustrate that the
      treatment of exclusion area has the most plant diversity in comparison with
      treatments of fallow, annual medic cultivation, wheat cultivation and range
      grazed.

PMID- 18819586
TI  - A 10 month old infant with nystagmus and strabismus.
AB  - This report present an infant with nystagmus, strabismus, salt and pepper and
      scars in funduscopy, calcification in Brain CT scan and high titer of Anti
      Toxoplasmosis antibody. A 10 month old infant that referred with nystagmus,
      strabismus after fever which appeared five months ago. In funduscopy of both
      eyes, salt and pepper and scars and in Brain CT scan multiple calcification were
      seen. The diagnosis of congenital Toxoplasmosis was established by positive serum
      Anti toxoplasma Ab (IgG) (> 400). Toxoplasmosis may present with only nystagmus
      and strabismus and physicians should consider this infection in the differential
      diagnosis of a abnormal eye movement.

PMID- 18819587
TI  - Relationship among leaf (Puccinia recondita Roberge ex Desmaz f. sp. tritici) and
      yellow (Puccinia striiformis Westendorp. f. sp. tritici) rust resistance and some
      agro-morphologic traits in wheat hybrids at seedling stage.
AB  - This research was carried out to determine if dominant morphological traits can
      be use instead of the rust resistance tests as marker characters for some agro
      morphologic traits both leaf (Puccinia recondita Roberge ex Desmaz. f. sp.
      tritici.) and yellow rust (Puccinia striiformis Westendorp f. sp. tritici)
      disease. For this, 13 wheat parent (4 are T. durum Desf. and 9 are T. aestivum
      L.) were used and three main agro-morphologic traits (Namely, Leaf Colour (LC)
      (Dark and light green, Dg and Lg, relatively); Auricle Colour (AC) (White and
      Red, Wh and Re, relatively) and Leaf Waxiness (LW) (Waxy and Non waxy, Wx and Nw,
      relatively) were investigated at the seedling stage. They were found as dominant
      and concluded that investigated traits could be used as a morphological marker
      character for the leaf and yellow rust disease resistance tests under greenhouse
      conditions without doing complex and risky rust tests. And determined that, these
      traits may be use effectively without doing the complex rust tests in the limited
      populations or for the pre-selections. Doing with this, it will be bring a great
      accuracy, successful, correction and speed to the rust disease studies and
      provides important and valuable information for the plant breeders and
      pathologists. In addition, knowing of the resistance type (genetic mechanism
      etc.) in wheat facilitates it will be make to find out the suit and most
      appropriate breeding and selection methodology/methodologies.

PMID- 18819588
TI  - Effects of Maghnian bentonite on physical properties of sandy soils under semi
      arid Mediterranean climate.
AB  - This research has for object to study the influence of clay addition, i.e.,
      Maghnian bentonite, like deposit clay, in the physical properties of sandy
      materials from Mostaganem plateau (North-West Algeria) submitted to salinity and
      sodicity. The first result was to show that the clay content changes drastically
      the physical properties of clay-sand mixtures. Important differences were
      observed as a function of the sand particle size distribution. At given clay
      content, the saturated Hydraulic Conductivity (HCs) was lower when the sand size
      was small and spread. For the coarse sand the salinity was maintained, even for
      high clay contents, a significant hydraulic conductivity. One of the main
      characteristics of Maghnia clay is the presence of calcium carbonates in the
      natural material. In comparison to that of Mostaganem clay of other deposit, it
      appears less sensitive to sodicity. An important aspect is the initial state of
      the clay when used in addition to sands, i.e., disturbance, conditions of
      preparation of sand clay mixtures and presence of associated components such as
      carbonates. Maghnia clay appeared to be adapted to the improvement of sandy
      soils, not because its mineralogical characteristics, but for its natural
      cationic form and obviously the presence of calcite in it.

PMID- 18819589
TI  - Genetic variation of wild rice populations from Thailand and the Lao PDR based on
      molecular markers.
AB  - The two wild rice species, Oryza rufipogon and O. nivara, which inhabit Thailand
      and the Lao PDR, are threatened with the loss of their natural habitats. The
      losses are primarily attributable to human intervention. Before this process
      advances, it is crucial to obtain basic information on the genetic variations of
      these species, so important knowledge about the current status of genetic
      variability. In this study, genetic variation within and between fourteen natural
      populations of the two populations from Thailand and Lao PDR was investigated at
      the DNA level by analysis of Polymerase Chain Reaction (PCR) mediate molecular
      markers. The results illustrated that wild rice from Thailand carried deletion
      (D) type ORF 100, but deletion and non-deletion type (ND) were found in wild rice
      samples from the Lao PDR. Five different plastid subtypes (7C7A, 6C8A, 7C6A, 6C7A
      and 9C7A) were found in the collected samples. Both polymorphism and pattern of
      distribution of p-SINE1-r2 in the two wild rice species were found among the
      populations. These data indicated that genetic variation existed in these natural
      populations of wild rice, suggesting that the strategies should be developed that
      are conducive to the conservation of wild rice in its natural environment.

PMID- 18819590
TI  - Effect of land preparation methods on growth, seed yields of Jasmine 105 paddy
      rice (Oryza sativa L.) and growth of weeds, grown in Northeast Thailand.
AB  - This experiment was carried out on a grower's paddy field, Ban Som Hoeng Village,
      Kantarawichai, Mahasarakham Province, Northeast Thailand with the use of Roi-Et
      soil series (Oxic Paleustults) in the rainy season of the 2006 (May to November)
      to investigate effect of land preparation methods on rice plant heights, amounts
      of weeds and seed yields of Jasmine 105 aromatic paddy rice (Oryza sativa L.).
      The experiment was laid in a Randomized Complete Block Design (RCBD) with four
      replications. The results showed that plant height due to treatments was
      significantly highest for T3 but T3 was similar to T2, whilst T1 (control) was
      the least. Mean values of dry weight of narrow leaf type of weeds, in most cases,
      were significantly lowest with T3 followed by T2 and T3, particularly at the
      final two sampling periods. Broad leaf type of weeds was significantly highest
      with T2 throughout the experimental period, whilst T1 and T3, in most cases, were
      similar. Unfilled seeds were significantly highest with T3 but similar to T1 but
      T2 was the lowest, whilst filled seeds were significantly highest with T3, both
      T1 and T2 gave a similar weight. Numbers of panicles m(-2) were significantly
      highest with T3 but T3 was similar to T2, whilst T1 was the least. Seed size or
      1000-seed weight was significantly highest with T3, whilst T2 and T1 were
      similar. Seed yield was highest and highly significant with T3 (1,136.25 kg ha(
      1)) but T3 was similar to T2 (1,083.31 kg ha(-1)), whilst T1 was the lowest
      (487.50 kg ha(-1)). Land preparation method of T3 treatment may be recommended as
      the first choice, whilst T2 may be used as an alternative choice.

PMID- 18819591
TI  - In vitro effect of garlic extract and metronidazole against Neoparamoeba
      pemaquidensis, page 1987 and isolated amoebae from Atlantic salmon.
AB  - Neoparamoeba pemaquidensis believed to be the most prevalent parasite of Atlantic
      salmon industry in Australia. In the present study, the in vitro effects of crude
      extract of garlic and metronidazole were investigated using a primary culture
      toxicity assay. Garlic extract appeared to be completely effective at killing a
      cultured strain (NP251002) of Neoparamoeba pemaquidensis in vitro at a dilution
      of 1:100 with in 24 h. The number of viable Amoebae after using garlic extract in
      lower dilutions (1:200, 1:400, 1:800, 1:1000) for 24 h, also were significantly
      lower than in the control group. Garlic extract was also efficacious at killing
      wild type Amoebae that isolated from the diseased fish showing clinical signs of
      AGD. Metronidazole had no clear effect against Neoparamoeba pemaquidensis
      (NP251002) even in a concentration of 50 mg L(-1) for 24 h. However some
      morphological changes have occurred in metronidazole-treated Amoebae after 5 days
      of exposure.

PMID- 18819592
TI  - Fumigant toxicity of citrus oils against cowpea seed beetle Callosobruchus
      maculatus (F.) (Coleoptera: Bruchidae).
AB  - In the present study, the effects of volatile components of Citrus paradisi, C.
      aurantium, C. limonium and C. sinensis peel essential oils were investigated on
      the cowpea adult bruchid, Callosobruchus maculatus (F.). The oils were extracted
      from the fruit peels using hydrodistillation. The results indicated that the
      citrus oils had high fumigant activity against adult beetles. The mortality of 1
      2 day-old adults increased with concentration and exposure time from 3 to 24 h.
      The oil of C. paradisi was more effective than those of C. aurantium and C.
      limonium (The LC50 values were 125, 145 and 235 microl L(-1) at 24 h exposure,
      respectively). The oil of C. sinensis proved to be least toxic (LC50 = 269 microl
      L(-1). The results suggested that citrus peel oils can be used as potential
      control measure against cowpea beetles.

PMID- 18819593
TI  - Chemical composition of raw fish consumed in Bahrain.
AB  - Nine species (Seriolina nigrofasciata, Siganus canaliculatus, Rhabdosargus
      haffara, Scomberomorus commerson, Liza alata, Epinephelus areolatus,
      Plectorhinchus sordidus, Lethrinus nebulosus and Penaeus semislcatus) of raw fish
      commonly consumed in Bahrain were analyzed for their proximate, mineral and heavy
      metal content. The protein content ranged from 17.9-21.8 g/100 g, fat content
      from 0.80-16.1 g/100 g and energy content from 87.1-216.7 kcal/100 g. The raw
      fish also had high levels of sodium (82-300 mg/100 g), potassium (210-400 mg/100
      g), phosphorous (200-280 mg/100 g), magnesium (23-47 mg/100 g) and zinc (0.0-2.2
      mg/100 g). Content of iron, calcium and copper were quite low. The species
      Penaeus semislcatus had low levels of both lead and mercury (<0.02 microg g(-1)).
      The maximum level of lead was 0.50 microg g(-1) and mercury was 0.20 microg g(
      1). One species (Rhabdosargus haffara) of fish had cadmium levels of 0.03 microg
      g(-1), while the rest of the fish had less than 0.02 microg g(-1). Overall, fish
      available in the market of Bahrain are a good source of some essential minerals.
      Furthermore, the heavy metal content is below the maximum permitted limits and
      can be safely consumed by the general public. However, monitoring of heavy metals
      in fish consumed in Bahrain should be done periodically.

PMID- 18819594
TI  - Evaluation of dyes decolourisation by the crude enzyme from Pleurotus sajor-caju
      grown on sorghum seed media.
AB  - The extracellular enzymes from Pleurotus sajor-caju were studied for lignin
      degrading enzyme patterns and dye decolourisation potential. Laccases are major
      ligninolytic enzymes excreted by the fungus. The results from a native-PAGE
      revealed that there were at least two isoenzymes. The crude enzyme had a pH and a
      temperature optimum at 6.0 and 40 degrees C, respectively when 2,2'-azino-bis-(3
      ethylbenzothiazoline-6-sulfonic acid) (ABTS) was used as substrate. The pH and
      thermal stability were at 5.0 and 30 degrees C. The pH optima for decolourisation
      of Indigo Carmine and Methyl Red were at 5.0 and 6.0, respectively. Indigo
      Carmine could be decolorized efficiently above 90% within 180 min, whereas Methyl
      Red could be decolorized only 3.5%. High efficiency decolourisation of Indigo
      Carmine makes this fungus to be a promise choice in biological treatment of waste
      water containing Indigo Carmine.

PMID- 18819595
TI  - Use of pulse trickles to reduce clogging problems in trickle irrigation system in
      Saudi Arabia.
AB  - Laboratory experiments were conducted at the Agricultural and Veterinary Training
      and Research Station, King Faisal University, Al-Hassa, Kingdom of Saudi Arabia
      to study the effect of pulse irrigation from a line source on sandy soil
      uniformly packed in soil tank using high flow rates. It was found that the
      increase in pulsed flows up to six times to that of the equivalent continuous
      flow can be used with little change to the soil wetting pattern. The water deep
      percolation reduced and horizontal spread increased with an increase in the
      pulsed flow up to twelve times to that of continuous flow (control treatment). A
      strong correlation was obtained between the water application rates and the
      vertical and horizontal advances which could be expressed as power function. The
      results showed an excellent potential to increase the emitter sizes up to 2.4-3.5
      times and the emitter cross section area up to 6.0-12.0 times than the normal
      size for reducing the trickle clogging problem. Empirical analysis of the
      vertical and horizontal advance shows that both of these parameters can be
      expressed as a power function.

PMID- 18819596
TI  - Estimation of genetic parameters and environmental factors on early growth traits
      for Lori breed sheep using single trait animal model.
AB  - The effects of different environmental factors and estimation of genetic
      parameters on early growth traits for Lori breed sheep including birth weight,
      weaning weight and body weight at 6 months of age using 19960 records from 35
      herds of Lorestan Jahad Agriculture Organization were studied in the cities of
      Aleshtar, Khorramabad and Poldokhtar from 1995 to 2003. The effect of herd, sex
      of lambs, dam age and birth year on all traits and birth type had significant
      effect only on weaning weight. Different single trait animal models estimated the
      components of direct additive genetic variance, maternal genetic variance and
      maternal permanent environment variance through restricted maximum likelihood
      using environmental factors as a fixe effect and different random effects. The
      results showed that direct additive genetic effect had additionally significant
      effect on all traits moreover maternal additive genetic and maternal permanent
      environment effects. Results also revealed that the maternal permanent
      environment variance for all traits is higher than maternal genetic variance.
      Also the direct heritability for all traits was higher than maternal
      heritability. Estimation of the direct heritability from the birth to 6 months of
      age showed a reducing trend that could arise from high dependence of birth and
      weaning weight on maternal environment conditions as compared with the age
      conditions afterward. The genetic assessment of growth traits in Lori breed sheep
      without inclusion of maternal effect in animal model causes decreased selection
      accuracy and incorrect genetic assessment of the lambs.

PMID- 18819597
TI  - Cultivar and nitrogen splitting effects on Amaranth forage yield and weed
      community.
AB  - A 2 year field study was carried out at Agricultural Faculty of Shahid Chamran
      University of Ahvaz (Iran), in order to evaluate the response of Amaranth
      cultivars and weed dynamic to N splitting methods. Three Amaranth cultivars
      (i.e., Amont, Trigin and Plainsman) were grown in three N splitting methods
      (i.e., Commonly, Equal and Semi-equal) that being applied at planting, 12th leaf
      appearance and stem elongation. A split plot design replicated three times was
      used which Amaranth cultivars and N splitting methods were arranged in main and
      sub plots, respectively. Results showed that the highest forage yield was
      obtained for Trigin with Equal N splitting (i.e., 31.2 t ha(-1)) and Plainsman
      with Semi-equal N distribution (i.e., 3.8 t ha(-1)) the lowest. Also, the maximum
      and minimum protein content (%) were obtained for Trigin with Equal N splitting
      (16%) and Amont with commonly N splitting (11.9%), respectively. It was found
      that just Trigin with Equal N splitting treatment was the best treatment for both
      forage quality and quantity yield. Moreover, the weed communities and dominant
      species changed in response to various N splitting methods and Amaranth cultivars
      traits. Plainsman with Semi-equal N splitting treatment was the unfavorable
      treatment for both crop yield and weed infestation. Based on these results it is
      recommend that N splitting method be applied mainly as an Equal form in Trigin
      amaranth cultivar, to enhance crop forage yield and reduce weed infestation.

PMID- 18819598
TI  - Method and quantity of liquid formulation of phosphobacteria required for seed
      inoculation.
AB  - The survival of vegetative and sporulated cells of the Bacillus cultures on the
      seeds of the crop plants was tried in different combinations. One milliliter
      inoculum with 1 mL adhesive combination or sterile water showed better results
      followed by 1.5 mL inoculum with 0.5 mL adhesive or sterile water. The population
      of 5.5x10(5) cfu seed(-1) on black gram, 10.5x10(5) cfu seed(-1) on soybean and
      6.5x10(5) cfu seed(-1) on maize were observed after 12 h of incubation in 1 mL
      sporulated inoculum mixed with 1 mL of rice gruel. The sporulated inoculum along
      with rice gruel favoured the adherence of the regenerated cells as rice gruel is
      rich in nutrient content.

PMID- 18819599
TI  - Water stress induced by polyethylene glycol 6000 and sodium chloride in two maize
      cultivars.
AB  - Responses of growth and germination to water stress induced by PEG 6000 and NaCl
      in two maize (Zea mays L.) cultivars 704 and 301 were studied. Water stress was
      generated by additions of PEG 6000 or sodium chloride to the root medium. Water
      potentials were: zero as control and -0.15, -0.49, -1.03 and -1.76 MPa as
      treatments. After 24 h treatment, the roots and shoots length and dry weight were
      of plants determined. In water stress, roots and shoots length and dry weight
      decreased at both treatments in both varieties. The germination is inversely
      proportional to the NaCl and PEG concentrations, it means that 704 and 301
      cultivars of maize showed a reduction in germination with an increasing in NaCl
      or PEG concentrations induced water deficit, but this reduction in NaCl treatment
      were higher than PEG treatment. At treatment by PEG, the germination was severely
      decreased at -1.03 MPa. At treatment by NaCl no germination occurred at -1.03 in
      301 var. and germination was very low at -1.03 MPa in 704 var., no germination
      occurred at -1.76 MPa in both varieties at both treatments. Decrease of
      germination in 704 variety was higher than 301 variety.

PMID- 18819600
TI  - Comparison of four induced molting methods based on subsequent performance and
      welfare of Single Comb White Leghorn hens.
AB  - A total of 400 Single Comb White Leghorn hens at 80 weeks of age were used in
      present study. Four treatment groups that were consisted of six replications with
      10 hens per each replication were considered. In the first treatment, food and
      water were removed for the first 2, 4, 6 and 8 days. However, on days 3, 5, 7, 9
      and on day 10 until day 28 hens were fed 45 g of food per hen (ON-OFF group). In
      the second and third groups, food was withdrawn for 10, 14 days, respectively and
      oyster shell and water were provided for ad libitum until day 28 (California and
      North Carolina treatments (CAL, NC groups)). The last group (full-food treatments
      (FF group)) was the hens that were non-food-deprived and were fed corn molt diet
      for 28 days ad libitum. In all treatment groups at day 29, hens were returned to
      a full food layer ration and received 16 h of light day(-1). Body weight, egg
      production, egg weight, relative eggshell weight, internal egg quality, egg
      specific gravity and mortality were determined. Differential leukocyte count and
      antibody response were also measured. The results demonstrated that induced
      molting increased egg production according to pre-molt egg production. There was
      not a significant difference in the rate of egg production during the peak period
      of post molt production for treatments. No significant differences were detected
      in differential leukocyte counts and antibody response against Sheep Red Blood
      Cell (SRBC) between treatments at pre molt and post molt of the experiment. This
      study indicated that diets with high corn level (FF groups) are effective and
      simplified nonfood removal procedure for welfare molting hens.

PMID- 18819601
TI  - An appropriate plot area for analyzing canopy cover and tree species richness in
      Zagros forests.
AB  - In order to make the sampling procedure more efficient and more accurate to study
      the tree species richness and canopy cover, the appropriate plot size was
      calculated in the this study. The sampling was carried out using 48 four-hectare
      plots, each with 13 sub-plots of different plot sizes and 7 one-hectare plots,
      each with 7 sub-plots. The result of this study showed that 300 ARE plot size was
      determined as the best area for 1-5% density class, 125 ARE plots for 5-10%
      class, 150 ARE for 10-25% class, 100 ARE for 25-50% class and 75 ARE plot size to
      sample >50% density class, in 95% confidence level. Consequently, using 100 ARE
      sampling plots is suggested for all density classes in central Zagros forests.

PMID- 18819602
TI  - Prediction breeding value and genetic parameter in Iranian Holstein bulls for
      milk production traits.
AB  - Data set included records of 43303 cows for first lactation. Records were
      collected from 2000 to 2006 in Animal Breeding Center of Iran Studied traits were
      yield of milk, fat, protein and percentage of fat and protein. Total number of
      animal was 197561 individual in pedigree. Genetic and phenotypic parameters were
      estimated with REML method under single trait Animal Model. Breeding values were
      predicted with BLUP procedure. The model for the analyses included the factors
      herd-year-season as fixed factor (1694 levels), animal as random effect and age
      at calving as co variable with minimum and maximum of 23 and 36 month.
      Respectively the estimated heritabilities were 0.35 (+/-0.02), 0.33 (+/-0.02),
      0.31 (+/-0.017), 0.28 (+/-0.02), 0.27 (+/-0.016) for milk, fat, protein yield,
      percent of fat and protein. Mean of breeding values of sires were 180.2 (+/
      28.2), 3.7 (+/-1.26), 2.3 (+/-1.06), -0.036 (+/-0.014) and -0.028 (+/-0.009) for
      milk, fat, protein yield, percent of fat and protein, respectively.

PMID- 18819603
TI  - The study of vitelline gland of Haploporus lateralis (Digenea: Trematoda).
AB  - The study of vitelline glands of digenean Haploporus lateralis, indicates that
      the glands consist of vitelocytes in various stages of maturation. The
      cytoplasmic process of nurse cells which surrounded the vitelline lobes, intrude
      between vitelocytes and surround them. Immature vitelline cells are
      undifferentiated, they possess small amount of cytoplasm and large nucleus. The
      synthesis of shell globules begin in the maturing vitelline cells. Increasing
      numbers of vitellocytes reach develop of mature vitelline cells. The cytoplasm of
      mature vitelline cells is filled with shell globules. Mature vitelline cells
      usually found in the center of vitelline lobe. They release into the vitelline
      duct and vitelline reservoir. The vitelline reservoir and duct are lined with a
      syncytial epithelium. Basement membrane is present between nurse cells and
      vitelline cells.

PMID- 18819604
TI  - Molecular aspects of drought tolerance in bread wheat (T. aestivum).
AB  - In order to evaluate molecular indices of drought tolerance and selection of
      drought tolerance genotypes in bread wheat a randomized complete block design was
      carried out with three replications in the field of research station of Sararood,
      Kermanshah, Iran. Positive significant correlation coefficient was observed
      between grain yield and proline, soluble sugar and total protein under rainfed
      condition. Based on the grain yield, proline content, soluble sugar and total
      protein the genotypes were classified into four clusters using cluster analysis
      and UPGMA method. Genotypes numbers 4, 9, 10, 11, 18 and 19 in the first clusters
      indicated the highest performance.

PMID- 18819605
TI  - Irrigation frequencies and corn (Zea mays L.) yield relation in northern Turkey.
AB  - A field experiment was conducted during summer season of 2005 at the Research
      Station (altitude 180 m above sea level, 41 degrees 21' N and 36 degrees 15'E)
      Faculty of Agriculture, Ondokuz Mayis University, Samsun, Turkey. Experiment
      consisted of three irrigation levels and a non-irrigation level. Drip irrigation
      treatments consisted of three soil water deficits in the 90 cm soil profile depth
      was replenished to field capacity. Irrigation treatments were A: no irrigation,
      B: irrigation at 50% of available soil water capacity, C: irrigation at 30% of
      available soil water capacity, D: irrigation at 15% of available soil water
      capacity. The average seasonal water use values ranged from 257.14 to 285.71 mm
      in corn treatments. Irrigation frequencies (intervals) significantly affected
      corn crop yields. The average corn grain yields varied from 7.98 to 29.16 t ha(
      1). The treatment D was recorded significantly higher corn grain yield 29.16 t
      ha(-1) compared to B (21.59 t ha(-1)); C (19.15 t ha(-1)) and A (7.98 t ha(-1)),
      respectively. According to research results, the maximum corn grain yield was
      obtained when the corn plants were irrigated at 15% of available soil water
      capacity to field capacity.

PMID- 18819606
TI  - The potential toxicity of diazinon on physiological factors in male rat.
AB  - Diazinon is an Organophosphate Insecticide (OPI) is commonly used in agriculture
      to protect of crops and to control pests in home gardens and farms. Many
      alterations observed by diazinon have been described, such as; alterations in
      blood factors (RBC, Hb and Hct), plasma testosterone and glucose levels. We
      selected 12 albino Wistar rats weighting between 220-280 g were divided into two
      experimental groups, as follow, control group and diazinon treated group. The
      effects of diazinon, on rat interstitial cell testosterone production, blood
      factors and plasma glucose levels were evaluated. Male rats were treated orally
      with a single dose of 1/4 LD50 of diazinon. Animals received treatment for 28
      days. Present results indicated that in diazinon treated group, plasma glucose
      and testosterone levels increased compared to control. Also in diazinon group,
      reduce of blood factors were observed than control. In conclusion, diazinon
      disturbs the synthesis of testosterone and glucose release from liver into blood
      and it led to anemia.

PMID- 18819607
TI  - Study for determination of industrial water corrosivity in Kashan Fajre Sepahan
      Galvanizing Mills during 2005-2006 Iran.
AB  - This research was carried out in Kashan Fajre Sepahan Galvanizing mills (KFSGM)
      for evaluation of water corrosivity during 2005-2006. A total of 18 samples were
      taken from various points of the water supply system for testing the specific
      parameters and calculation Langelier Index (LI), Ryznar Index (RI) and Pukorious
      Index (PI). This research showed that in raw water (sand filter effluent) LI were
      positive as well as RI and PI were lower than 7 which means that mentioned water
      is not corrosive. Also LI in treated water by reverse osmosis process was
      negative and RI and PI were higher than 7, so, this water has corrosive
      properties. Finally, calculated indexes indicate that according to LI,
      conditioned water is not corrosive but based on RI and P. this water tend to
      corrosivity which this findings is compatible with literature review statement.
      So it is recommended that, for water conditioning addition of preservative
      chemicals to be continued but at the same time another alternatives such as pH
      adjustment, air stripping and deoxygenating, control of carbonate concentration
      and split flow treatment should be studied.

PMID- 18819608
TI  - Phenotypic diversity in Terminalia catappa from South Western Nigeria.
AB  - The diversity amongst Teminalia catappa population in two different locations in
      the Lagos area of South Western Nigeria was investigated. Forty trees were
      sampled for twenty eight quantitative and twelve qualitative characters.
      Variability was observed in qualitative characters such as leaf shape and ripe
      fruit colour. Quantitative characters analyzed using multivariate statistical
      analysis showed high intraspecific variability for most of the characters
      determined. Cluster analysis using the unweighted pair group method using
      arithmetic mean (UPGMA) method revealed four main clusters which were not based
      on location of collection but on morphological characters. The trees were grouped
      into the main clusters based mainly on plant architecture. The result from the
      trees studied showed that selections based on traits such as fruit size, fruit
      colour and leaf sizes can be undertaken for future improvement or development of
      this tree crop in Nigeria.

PMID- 18819609
TI  - Nutritional evaluation of Sterculia setigera seeds and pod.
AB  - The results obtained on analysis of the seeds and pods of Sterculia setigera for
      their nutritional composition revealed that while the seed sample has high crude
      protein, crude fibre, carbohydrate and fat contents, their contents in the pod
      sample was very low. The analysis of the mineral profile reveals that the seed of
      Sterculia setigera is rich in sodium, iron, zinc and manganese. Conversely, the
      mineral composition of the pod is low.

PMID- 18819610
TI  - Blood lipid and lipoprotein profile of female athletes with respect to their jobs
      and nutrients intake.
AB  - There is general believe that exercise may results in changes that likely reduce
      the risk of developing cardiovascular disease and may slow the progression of
      established coronary artery disease. Chronic cardiovascular training results in
      changes in lipoproteins and apolipoproteins that reflect adaptation to the
      increased metabolic demands imposed by frequent, vigorous exercise. Moreover, the
      alterations in lipoproteins vary according to level of physical conditioning and
      intensity of exercise. One hundred three pre-menopausal physically active women
      ages 20-50 years old which have been exercising for at least 6 months involve in
      this study. Upon entering the study subjects were asked to complete
      questionnaire, regarding personal health and diet history (24 h recall plus 7
      days food frequency list). Total calorie intake, level of carbohydrate, protein
      and fat in the subjects' diet were analyzed. In addition the concentration of
      women's plasma triglycerides, total cholesterol, LDL-C and HDL-C were also
      measured and compared with normal value. The results of the present study showed
      that, the mean total caloric intake of women were 1812.54 kilocalories, where
      their carbohydrate, protein and fat intake were 67.28, 12.83 and 19.89% of their
      total calories, respectively. The average age, weight, height and Body Mass Index
      (BMI) of the women involved in the study were, 30.81+/-8.87 years, 57.85+/-7.79
      kg, 160.32+/-5.36 cm and 22.53+/-2.82 kg m(-2), respectively. Plasma lipid and
      lipoprotein concentration of women were also in normal range with the lowest in
      those who exercise for more than one year and physical education teacher.

PMID- 18819611
TI  - Bovine liver abscesses pus and the status of some important minerals.
AB  - This research was conducted to determine selenium, copper, zinc, iron, calcium,
      phosphorous and magnesium concentration in the pus of cow liver abscess. The
      liver has a large reserve of function and approximately three-quarters of its
      parenchyma must be rendered inactive before clinical signs of hepatic dysfunction
      appear. Local suppurative infections of the liver cause significant losses in
      feedlot and grain-fed cattle because of the frequency ofrumenitis in those cattle
      leading to hepatic abscess formation. Also we know some minerals that can alter
      and uphold the specific immunity. At the presence of adequate amount of zinc, the
      formation of hepatic abscess may reduce. For this reason and to determine the
      mineral concentration in pus, the present study was designed on 40 slaughtered
      cattle with liver abscess in Shahrekord district. For measuring the minerals
      concentration, Potentiometric Stripping Analyzer (PSA), atomic absorption
      spectrometry were used. Results showed that the concentration of Se, Zn, Fe, Cu,
      Ca, P and Mg in pus were 0.551A+/-0.046 (mg kg(-1)), 6.41A+/-2.32 (mg kg(-1)),
      18.18A+/-14.03 (mg kg(-1)), 6.63A+/-4.83 (mg kg(-1)), 221.8A+/-85.82 (mg kg(-1)),
      0.85A+/-0.32 (g kg(-1)) and 40.64A+/-21.72 (mg kg(-1)), respectively. The
      concentration of mentioned minerals in liver parenchyma's were determined 1.06A+/
      0.15 (mg kg(-1)), 82.91A+/-32.22 (mg kg(-1)), 62.29A+/-22.12 (mg kg(-1)),
      39.22A+/-28.17 (mg kg(-1)), 0.12A+/-0.04 (g kg(-1)), 1.81A+/-0.56 (g kg(-1)) and
      0.15A+/-0.07 (g kg(-1)), respectively. For determining the correlation between
      mineral concentration in pus and liver parenchyma, Pearson correlation was used
      at The level of p<0.05. The correlation between pus Fe and Cu and also Ca and Se
      were significantly positive (pvalue = 0.000228, r = +0.871) and negative (pvalue
      = 0.0305, r = -0.623), respectively. In liver parenchyma the correlation between
      Zn and Ca (pvalue = 0.0487, r = 0.535) and also Fe and Cu (pvalue = 0.0317, r =
      +0.596) were significantly positive.

PMID- 18819612
TI  - Isolation of Streptococci from milk samples of normal, acute and subclinical
      mastitis cows and determination of their antibiotic susceptibility patterns.
AB  - Streptococci are frequently isolated from bovine mastitis in dairy cows with only
      limited information available on the antimicrobial susceptibility of these
      organisms. A total of 42 Streptococci isolated from 148 milk samples of normal,
      sub acute and acute bovine mastitis cases. Overall, 35% of the strains tested
      were Streptococcus dysgalactiae, Streptococcus agalactiae 26%, Streptococcus
      uberis 18 and 4% were Enterococcus sp. Differences between the number of
      isolations in acute and sub acute groups were statistically significant, (p<0.5).
      The antimicrobial susceptibility for these organisms was determined for the
      following antimicrobial agents: cephalexine, penicillin, clindamycin,
      cloxaciline, gentamicin, streptomycin, amoxicillin, tetracycline, kanamycin,
      oxytetracycline, ampicillin, chloramphenicol and erythromycin. S. agalactiae, S.
      dysgalactiae, S. uberis and Enterococci demonstrated high level of resistance
      against streptomycin, penicillin and cloxaciline. Low level of sensitivity to
      other tested antimicrobials was demonstrated.

PMID- 18819613
TI  - Ovarian pregnancy: a case report.
AB  - A case report of ovarian pregnancy is presented. A 38 year old woman, gravida 3
      para 2, was admitted to the hospital for suspected ectopic pregnancy, with
      vaginal bleeding at 12 weeks after her last menstrual period, associated with
      pelvic pain. An ultra-sonography led to the diagnosis of ovarian right ectopic
      pregnancy with dead fetus associated with a compartmentalized hemoperitoneum.
      Unilateral oophorectomy was carried out by laparotomy. Histological studies
      confirmed an ovarian pregnancy.

PMID- 18819614
TI  - Leeching in the history--a review.
AB  - Leeching has enjoyed a good reputation in the past where it had been used in
      various ailments from fevers to flatulence. The present day scientists have
      limited its role and the leeching nowadays is being used only in microsurgeries
      to relieve the venous congestion. This study was designed to explore the
      possibility of revival of the leech therapy (leeching) which is still being used
      traditionally as therapeutic agent in various ailments. Leeching is not the
      outcome of the medieval period but has been in use during the times when there
      was no concept of the disease and medicament. The earliest clearly documented
      record of leeches being used for remedial purpose appears in a painting in an
      Egyptian Tomb of around 1500 BC. The journey of the leech therapy reached its
      zenith in 17th and 18th century AD in Europe while as during the Arab era the
      leeches were used medicinally but only for the bloodletting. During the 17th and
      18th century AD there was shortage of leeches in certain European countries due
      to its rigorous use. During early 20th century AD when germ theory was put
      forward and medical fraternity believed that every disease has its origin from
      germs and the era of antibacterial therapy gained a pace, the leech therapy was
      considered the myth of the past. It was in 1970's that the leech therapy was
      revived by only limited to the microsurgeries to relieve venous congestions.
      During the 21st century there were certain studies when the leeches were tried in
      certain ailments like arthritis etc. and the Food and Drug Authority of USA (FDA)
      gave permission for sale and use of leeches in USA but limited its use in
      microsurgeries and plastic surgeries only. The aim of this study was to explore
      different diseases where the role of leech therapy can be seen and clinical
      trials can be started in this direction. Although the researchers in Regional
      Research Institute of Unani Medicine, Srinagar, Kashmir, India working under the
      aegis of Central Council for Research in Unani Medicine started the clinical
      trials for leech therapy in frost bite way back in 1999, but there are certain
      unexplored areas where leech therapy can prove beneficial and need is to take up
      the studies on other disease on larger sample size.

PMID- 18819615
TI  - An analysis on flavonoids, phenolics and organic acids contents in brewed red
      wines of both non-skin contact and skin contact fermentation techniques of Mao
      Luang ripe fruits (Antidesma bunius) harvested from Phupan Valley in Northeast
      Thailand.
AB  - The experiment was carried out at the Department of Biotechnology, Faculty of
      Technology, Mahasarakham University, Northeast Thailand during the 2006. The
      study aimed to determine amounts of flavonoids, phenolics and organic acids in
      ripe fruits and brewed red wines of both non-skin contact and skin contact
      winemaking techniques where Mao Luang ripe fruits of both Fapratan and Sangkrow2
      cultivars were used. The experiment was laid in a Completely Randomised Design
      (CRD) with four replications. The results showed that mean values of primary data
      of fresh Mao Luang ripe fruits on weight of 100 berries (g) and mean values of
      juice:solids, pH, total soluble solid (TSS, 0brix), total organic acids (TOA, mg
      L(-1)), TSS:TOA (%), total flavonoids contents (TFC, mg L(-l)), total phenolic
      acids (TPA, mg L(-1)), total procyanidins contents (TPC, mg L(-1)) and reducing
      sugar (g L(-1)) were 65.62, 3.28, 3.51, 16.50, 49.36, 28.10, 397.90, 76.04,
      156.21 and 184.32, respectively. Skin contact Mao Luang red wine gave higher
      amounts of flavonoids, phenolic acids, anthocyanins of procyanidin B1 and
      procyanidin B2, organic acids than non-skin contact red wine. The differences
      were highly significant. Furthermore, ethanol (%) and total acidity (g L(-1)
      citric acid) were much higher for skin contact wine than non-skin contact wine
      but a reverse was found with total soluble solids (0brix), pH where non-skin
      contact wine gave higher mean values than skin contact wine.

PMID- 18819616
TI  - Genetic diversity of storage proteins in cultivated buckwheat.
AB  - Prolamin and albumn variations of the storage proteins in 76 cultivated buckwheat
      accessions (55 accessions of Fagopyrum tataricum, 21 accessions of F. esculentum)
      from 7 countries were characterized by A-PAGE and SDS-PAGE, respectively, for the
      purpose of evaluating the genetic diversity of cultivated buckwheat at the level
      of proteins. A total of 18 prolamin bands were detected, among which 88.89 %
      bands were polymorphic. The number of albumn bands based on SDS-PAGE observed in
      accessions ranged from 4 to 10. Most intense bands were in the range of molecular
      weights from 29 to 97.2 kDa. The average of genetic similarity coefficient based
      on prolamin bands was 0.784 (in F. tataricum and F. esculentum were 0.892 and
      0.681, respectively), while on prolamin and albumn bands was 0.742 (in F.
      tataricum and F. esculentum were 0.864 and 0.633, respectively). Accessions of F.
      tataricum and F. esculentum showed significant interspecific variation in the A
      PAGE and SDS-PAGE profile of the storage proteins. The cluster analysis indicated
      that all the accessions could be divided into 3 groups and 3 subgroups. The
      genetic variations among cultivated buckwheat accessions were associated with
      their geographic origins in some degree.

PMID- 18819617
TI  - Effects of monensin and increasing crude protein in early lactation on
      performance of dairy cows.
AB  - Twenty-four Holstein dairy cows were used to evaluate the singular and combined
      effects of different level of crude protein and monensin treatments during the
      early lactation on digestion and milk yield of dairy cows. The experiment was
      designed as completely randomized with a 3x2 factorial arrangement of treatments.
      The factors were three Concentrations of CP supplement (19.5, 21.4 and 23.4% of
      dry matter) and two levels of monensin (0 and 350 mg per cow per day). This
      experiment consist of three periods and each period was 3 week in length.
      Monensin did not affect DMI, milk yield, lactose and SNF but it reduced milk fat
      and protein percentage. Monensin premix significantly decreased rumen ammonia but
      rumen pH and microbial protein synthesis was not affected by monensin treatment.
      Although, Monensin treatment increased apparent digestibility of DM, NDF, ADF,
      CP, but they were not significantly. Increasing dietary CP, improved milk and
      protein production, but did not alter the other components of milk. Digestibility
      of NDF, ADF, CP were improved by increasing dietary CP. Increasing diet CP from
      19.5 to 21.4% did not significantly increase ruminal ammonia, but increasing to
      23.4% have significant effect on it. There was a linear relationship between
      level of crud protein in the diet and urine volume excretion. Microbial protein
      synthesis was affected by increasing CP level; on this way maximum protein
      synthesis was achieved in 21.4% CP.

PMID- 18819618
TI  - Contributions to the moss flora of Artvin region (Hatila Valley National Park
      Turkey).
AB  - Field studies were organized for exploring the moss flora of Hatila Valley
      National Park of Artvin (Turkey) during spring-summer period in 2005-2006. The
      taxonomic survey yielded eighty-five moss taxa o(comprises of seventy-nine
      species, six varieties) belonging to 44 genera of 16 families in Hatila Valley
      National Park of Artvin, Turkey. Bryum rubens Milt., Dicranodontium uncinatufm
      (Harv.) A. Jaeger., Eurhynchium hians var. rigidum (Boul.) Dull., Hypnum
      jutlandicum Holmen and Warncke, Rhynchostegiella jacquinii (Garov.) Limpr. and
      Pseudocrossidium hornschuchianum (Schultz) R. H. Z ander are new records for A4
      grid square (40 degrees-42' N, 38 degrees-42' E) determined. All taxa were found
      for the first time in Artvin. For every each taxon, the habitat pattern and
      distribution data are presented.

PMID- 18819619
TI  - Comparative study of the effects of gentamicin, neomycin, streptomycin and
      ofloxacin antibiotics on sperm parameters and testis apoptosis in rats.
AB  - The aim of this study was to investigate the comparative effects of
      aminoglycosides and fluoroquinolones on testis apoptosis and sperm parameters in
      rats. Fifty male Wistar rats were randomly divided into control (n = 10) and
      experimental (n = 40) groups. The experimental groups subdivided into four groups
      often. Each received 5 mg kg(-1) (IP) gentamicin, 50 mg kg(-1) (IP) neomycin, 40
      mg kg(-1) (IP) streptomycin and 72 mg kg(-1) (IP) ofloxacin daily for 14 days,
      respectively; however, the control group just received vehicle (IP). In the
      fourteenth day, rats were killed and sperm analyzed for sperm parameters. Testis
      tissues were also prepared for TUNEL assay for detection of apoptosis. There was
      a significant decrease in sperm count, viability and motility in all of
      experimental groups when compared with control group. Although in streptomycin
      group these parameters were less decreased than in the other experimental groups.
      The apoptotic cells were significantly increased in all experimental groups when
      compared with those seen in the controlled group. Gentamicin, neomycin and
      streptomycin and ofloxacin have negative effects on sperm parameters and testis
      apoptosis in rats. However, these side effects are less seen in the streptomycin
      group. Therefore, it is recommended that usage of this drug have fewer side
      effects on male fertility.

PMID- 18819620
TI  - Evaluation the effects of dextromethorphan and midazolam on morphine induced
      tolerance and dependence in mice.
AB  - The main aim of this study was to evaluate the effects of dextromethorphan and
      midazolam and their combination on morphine tolerance and dependence in mice. In
      the present study, different groups of mice were rendered randomly and received
      morphine (50 mg kg(-1), s.c.), morphine (50 mg kg(-1), s.c.) + Dextromethorphan
      (25, 50 and 75 mg kg(-1), i.p.), morphine (50 mg kg(-1), s.c.) + midazolam (0.5,
      1 and 2 mg kg(-1), i.p.), morphine (50 mg kg(-1), s.c.) + [Dextromethorphan (25
      mg kg(-1), i.p. ) + midazolam (0.5 mg kg(-1), i.p.)] once a day for four days.
      Tolerance was assessed by administration of morphine (9 mg kg(-1), i.p.) on fifth
      day. Withdrawal symptoms (markers for dependence) was assessed by administration
      of naloxone (4 mg kg(-1), i.p.) 2 h after co-administration of morphine with
      either Dextromethorphan or midazolam or their combination. Results showed that
      pretreatment with Dextromethorphan or midazolam decreased the degree of tolerance
      and withdrawal symptoms significantly. Additionally co-administration
      ofDextromethorphan and midazolam couldn't decreased the tolerance and dependence
      significantly. From these results it may concluded that Dextromethorphan and
      midazolam alone or in combination could prevent the development of morphine
      induced tolerance and dependence. These effects can be related to the N-Methyl-D
      Aspartate (NMDA) receptor antagonist behavior of Dextromethorphan and GABA
      receptor agonist property of midazolam.

PMID- 18819621
TI  - Preventive effects of flaxseed and sesame oil on bone loss in ovariectomized
      rats.
AB  - A study was designed to examine the effects of dietary flaxseed oil (FO) and
      sesame oil (SO) which are rich successively in n-3 and (n-9 and n-6) on
      biochemical parameters and histological status of bone. Sixty-four 90-day-old
      female wistar rats were randomly assigned to 6 groups: sham-operated rat (sham)+
      control diets, ovariectomized rat (OVX) + control diets, OVX + 7% FO, OVX + 7%
      SO, OVX + 10% FO, OVX + 10% SO. After 4 weeks of treatments, rats were
      euthanized; blood and tissues were collected for analyses. Markers of bone
      formation which is alkaline phosphatase activity and markers of bone resorption
      which is tartrate resistant acid phosphatase activity were measured. Present
      results showed that OVX increased significantly ALP and TRAP activity and the
      examination of bone tissue showed disruptive and lytic bone trabeculae. Animals
      fed 10% FO and 10% SO of fat reduced these parameters and improved bone
      microarchitecture. Whereas, there was no improvement in biochemical and
      histological states in OVX rats that received 7% of PUFAs successively provided
      from FO and SO diets. In conclusion, our results are encouraging because they
      suggest that PUFAs intake may help to prevent osteoporosis associated with
      estrogens deficiency. However, further studies are needed to determine the
      mechanism by which a diet rich in n-3 or lignans modulate bone tissue.

PMID- 18819622
TI  - Vitamin A status of pregnant women in Calabar metropolis, Nigeria.
AB  - The vitamin A status of 101 pregnant women attending clinic at the University of
      Calabar Teaching Hospital (UCTH), Calabar, Nigeria was assessed based on 24 h
      dietary recall, serum retinol concentration, history of night blindness, physical
      appearance and clinical eye signs. The study revealed that the mean dietary
      vitamin A intake of the respondents (2645.31 +/- 188.91 microg RE) and their mean
      serum retinol concentration (31.18 +/- 2.94 microg dL(-1)) were significantly (p
      < 0.05) higher than the FAO/WHO recommended intake and cutoff level for VAD. No
      case of night blindness, physical signs and symptoms, or clinical eye signs
      attributable to VAD was observed. There was a significant (p < 0.01) correlation
      between the amount of 24 h vitamin A intake of the women and their serum retinol
      concentration (r = 0.31). Also, women who had above 50% of their vitamin A intake
      from provitamin A sources had a significantly (p < 0.05) lower serum retinol
      concentration (23.10 +/- 21.12 microg dL(-1)) than those who had above 50% intake
      from preformed sources (49.54 +/- 42.63 microg dL(-1)) and those with about equal
      intake from both sources (55.75 +/- 30.80 microg dL(-1)). There was a significant
      (p < 0.05) and steady decline in serum retinol concentration in the women from
      the first trimester (37.79 +/- 6.65 microg dL(-1)), through the second trimester
      (35.12 +/- 4.72 microg dL(-1)), to the third trimester (21.54 +/- 1.46 microg dL(
      1)) of pregnancy.

PMID- 18819623
TI  - Growth enhancement of effective microorganisms for bioremediation of crude oil
      contaminated waters.
AB  - The bioremediation of polluted groundwater, wastewater aeration pond and biopond
      sites was investigated using bacteria isolated from these sites located at the
      oil refinery Terengganu Malaysia. Out of 62 isolates, only 16 isolates from
      groundwater (8) and wastewater aeration pond (3) and biopond (5) were chosen
      based on growth medium containing 1% (v/v) Tapis crude oil. Only four isolates;
      Acinetobacter faecalis, Staphylococcus sp., Pseudomonas putida and Neisseria
      elongata showed percentage biodegradation of crude oil more than 50% after 5 days
      using Mineral Salts Medium (MSM). The effect of physical parameters (temperature,
      pH and agitation) on growth by all four strains showed a maximum growth in MSM
      medium with 1% Tapis crude oil at 37 degrees C with pH 7 and agitation of 130
      rpm.

PMID- 18819624
TI  - Foliar micromorphology of Felicia muricata Thunb., A South African medicinal
      plant.
AB  - The foliar micromorphology of Felicia muricata (Thunb.) Nees (Asteraceae) was
      observed with the JEOL (JSM-6390LV) Scanning Electron Microscope (SEM). Both the
      abaxial and adaxial surfaces were characterized by anisocytic stomata which were
      more prevalent on the abaxial surface than the adaxial surface. The leaves have
      only one type of multicellular non-glandular trichomes that are long and
      cylindrical, tapering to a sharp point and running parallel to the leaf surface
      in the direction of the apices. Crystal deposits were also observed on the
      surfaces of the leaves near the stomata. Energy dispersive X-ray spectroscopy-SEM
      shows that Na, Al, Si, and K were the major constituents of the crystal analyzed.
      Since no glandular trichomes were present on the leaves of this herb, the
      bioactive components present in this plant may be produced in some other tissues
      in the leaf other than the trichomes.

PMID- 18819625
TI  - Controlled expression of cholera toxin B subunit from Vibrio cholerae in
      Escherichia coli.
AB  - The ctxB gene, the causative agent of cholera epidemic was successfully cloned
      from V. cholerae in E. coli. The insertion of the gene was confirmed by PCR as
      well as restriction digestion analyses. The sequencing results for the gene
      confirmed that the insert was in the correct orientation and in-frame with the
      P(BAD) promoter and it showed that the gene was 99% homologous to the published
      ctxB sequence. The CTB protein was successfully expressed in E. coli using the
      pBAD/His vector system. The expected protein of approximately 14 kDa was detected
      by SDS-PAGE and Western blot. The use of pBAD/His vector to express the cholera
      toxin gene in E. coli would facilitate future study of toxin gene products.

PMID- 18819626
TI  - The effects of methanolic extracts of ginger (Zingiber officinale) on human sperm
      parameters; an in vitro study.
AB  - This study was conducted on Zingiber officinale or ginger on motility, grading
      and morphological aspects of human sperm. Thirty human semen samples were
      obtained from the local hospital. The samples were swim up by Ham's F10. The
      samples (0.9 mL) were treated by 0.1 mL of ginger methanolic extracts (0.1, 0.2,
      0.4 and 0.6% concentration). Sperm motility, grading and morphology parameters
      were assessed using light microscope at 0, 2, 4, 8 and 24 h after treatment. Dose
      and time-dependent decreases in motility accompanied by concomitant decrease in
      grading 3 and 4 were noticed. Morphologic profiles of the sperms were changed
      under different doses of ginger on the basis of time of assess. These data
      indicate that some exhibits a lower percentage of motility and grading when
      methanolic ginger is added to semen fluid. According to the results it would be
      concluded that ginger can induce the toxic effects on sperm parameters.

PMID- 18819627
TI  - Nested PCR for the rapid detection of TB from pleural fluid at HUKM Malaysia.
AB  - The aim of the present study is rapid detection of tuberculosis from pleural
      effusion of suspected patients. Molecular technique Nested Polymerase Chain
      Reaction (PCR) was used for the purpose. A total of 67 pleural fluid collected at
      Hospital University Kebangsaan Malaysia during May 2005 to October 2006 were sent
      to Microbiology Laboratory enrolled in the study. Detection rate of Mycobacterium
      tuberculosis in pleural effusion was 0% by acid-fast bacilli (AFB) staining and
      1.5% by culture on Lowenstein-Jensen medium. Mycobacterium tuberculosis was
      detected by PCR in 9% of the cases. PCR of pleural fluid had 19% sensitivity and
      96% specificity, compared to AFB staining (0% sensitivity and 100% specificity)
      and culture (4% sensitivity and 100% specificity). PCR also has 67% Positive
      Predictive Value (PPV) and 72% Negative Predictive Value (NPV) in detecting
      Mycobacterium tuberculosis. Culture ofpleural fluid has 100% PPV and 71% NPV
      while AFB staining has 0% PPV and 31% NPV. This preliminary study showed that PCR
      is a rapid method for detection of Mycobacterium tuberculosis in pleural fluid
      but its sensitivity is not up the marked.

PMID- 18819628
TI  - Impacts of overgrazing in a long term traditional grazing ecosystem on vegetation
      around watering points in a semi-arid rangeland of North-Eastern Iran.
AB  - In this study, the effects of livestock overgrazing on vegetation of the critical
      area around livestock watering points in a traditional grazing ecosystem was
      investigated on a semi-arid rangeland in North-East of Iran. Transects were
      placed in 8 geographical directions around watering points and samples were taken
      systematically. In each experimental plot, 4 m2, percentage of canopy cover,
      abundance, density and species richness of vegetation were calculated. The
      results of this study showed that the percentage of canopy cover, density and
      species richness were changed with distance from watering points. Critical area
      immediately adjacent to watering points was dominated by unpalatable Peganum
      harmala and contained of ruderal species such as Sophora sp. Adjacent to this was
      a zone dominated by species of low palatability such as Acantholimon sp. and
      Hulthemia persica. In areas most distant from watering points relative importance
      of moderately palatable species such as Artemisia herba-alba increased. These
      results show the negative impacts of overgrazing on vegetation and palatability
      in a traditional grazing ecosystem, which may indicate the necessity of a
      monitoring programme, to manage livestock grazing and watering points in North
      East of Iran.

PMID- 18819629
TI  - No detected hepatitis B virus-DNA in thalassemic patients infected by hepatitis C
      virus in Kerman province of Iran.
AB  - This research was aimed to investigate the prevalence and clinical impact of
      occult HBV infection in thalassemic patients with chronic HCV infection. In this
      cross-sectional study we have totally examined 60 patients suffering HBV and HCV
      infections by PCR and RT-PCR methods, respectively, in Kerman province of Iran.
      ELISA technique (RADIM, Italy) was used to detect anti-HBc, anti-HBs and HBsAg.
      The serum level of liver enzymes (SGOT, SGPT, DB, TB and ALK) were analyzed in
      the HCV infected patients (MAN, IRAN). Statistical analyses performed using t
      test and Chi-square. We found that 27 cases (out of 60) were infected by HCV but
      HBV-DNA was not seen in HCV infected patients. Present findings also showed that
      none of samples were HBsAg positive but 9 (33%) (out of 27) HCV-RNA positive
      patients were anti-HBc positive and 11 (40.7%) were positive for anti-HBs. We
      found that SGOT, SGPT, DB, TB and ALK are above normal in 27 (100%), 19(70.3%),
      12(44.5%), 15 (55.5%) and 15 (55.5%) RNA-HCV positive patients, respectively. The
      prevalence of hepatitis C infection is very high in thalassemic patients and
      based on other studies our results showed that the prevalence of HCV infection in
      Kerman is more than other provinces of Iran. In contrast with other studies HBV
      DNA in these patients could not be detected, hence, it seems that occult HBV
      infection isn't frequent in Iranian thalassemic patients who suffering from
      chronic HCV infection.

PMID- 18819630
TI  - Effect of oral administration of fenitrothion on biochemical and hematological
      parameters in rats.
AB  - The aim of this study was to evaluate the effects of acute exposure to various
      doses of fenitrothion (FNT) on level of serum glucose, total protein,
      triglycerides (TG), total cholesterol (TC) and some hematological parameters. The
      study was conducted on 8-week-old male Wistar rats that divided into four groups
      (three experimental groups and one control group), were treated orally with
      different doses (25, 50 and 100 mg kg(-1)) of fenitrothion for 28 consecutive
      day. After treatment, blood samples were collected for biochemical and
      hematological studies. Present results demonstrated that exposed groups led to
      significant dose-dependent increase in serum glucose and cholesterol levels.
      Significant decrease was observed in some hematological parameters [Red Blood
      Cell (RBC) counts, Hemoglobin (Hb), Haematocrite (Ht) and Mean Corpuscular
      Hemoglobin (MCH) values]. Serum total protein and triglycerides were also
      decreased not significantly in exposed groups when compared with control.
      Generally, the degrees of observed variations were found to be dose dependent.

PMID- 18819631
TI  - The favorite dosage of garlic meal as a feed additive in broiler chickens ratios.
AB  - This experiment carried out as a completely randomized design with six treatments
      and 3 replicates pens of 100 birds each (total of 1800 birds). Treatments were
      consisted of a common corn-soybean meal based starter and grower diets
      supplemented by 0, 0.125, 0.25, 0.5, 1 or 2% garlic meal. At 1-21 days of age,
      daily feed intake per chicks influences by dietary garlic meal level so that the
      birds fed diets with 0.125 and 0.25% garlic meal had a significantly higher daily
      feed intake (p < 0.05) than birds fed 0.5% dietary garlic meal. At 22-42 days of
      age and the whole experimental period (1-42 days of age), garlic meal level
      didn't affect daily feed intake. No significant difference recorded for daily
      weight gain of experimentally birds at 1-21 days of age, But at 22-42 days of age
      and the whole experimentally period (1-42 days of age) the birds fed the control
      diet (free of garlic meal) and the diet containing the highest garlic meal dosage
      (2%) had a significantly lower daily weight gain in compare to other birds (p <
      0.05). At 1-21 days of age the birds fed diet supplemented with 0.5% garlic meal
      had a lower feed conversion ratio than the control birds (p < 0.05) but at 22-42
      days of age and the whole experimentally period (1-42 days of age) birds fed the
      control diet and the diet whit 2% garlic meal supplement showed a higher feed
      conversion ratios in compare with birds fed diets containing 0.125, 0.5 or 1%
      garlic meal. No significant differences were detected in carcass percentage and
      interior organs between birds fed experimental diets. The weight gain reduction
      in birds fed 2% dietary garlic meal means that herbal additives have their
      limitations too and needs more investigation.

PMID- 18819632
TI  - Time of initial detection of fetal structures and anatomic differentiation by
      using B-mode ultrasound examination in bitches.
AB  - Ultrasonographic examinations of 10 pregnant bitches with known breeding dates
      were made on successive days to establish the identifiable characteristics of
      pregnancy. Subsequent serial examinations were made to sonographically
      characterize normal canine prenatal development based about the first mating. The
      initial detection of the fetal and extra-fetal structures were as follows:
      gestational sac at day 17.88 +/- 1.13 (16-21); zonary placenta in the uterine
      wall at day 23.70 +/- 0.78 (23-25); embryo initial detection at day 22.80 +/-
      1.03 (21-24); heartbeat at day 23.0 +/- 0.94 (22-24); yolk sac membrane at day
      24.8 +/- 0.78 (24-26); amnionic membrane at day 26.81 +/- 0.60 (26-28); fetal
      movement at day 30.40 +/- 1.64 (28-32); stomach at day 33.40 +/- 1.07 (32-35);
      urinary bladder at day 34.90 +/- 1.19 (33-37); skeleton at day 35.10 +/- 0.73 (34
      36).

PMID- 18819633
TI  - Evaluation of clinical examination for differential diagnosis of lameness by
      navicular apparatus or heel pain in horses.
AB  - To evaluation of clinical examination for differential diagnosis of navicular
      region pain from other forms of palmar heel pain in the forelimb in horses the
      present study was undertaken. Thirty four horses with lameness referable to the
      palmar aspect of the hoof based on their response to the palmar digital nerves
      analgesia were divided into 2 groups based on their response to both distal
      interphalangeal joint and navicular bursa analgesia. Horses that were profoundly
      improved by both analgesic blocks (distal interphalangeal joint and navicular
      bursa) were considered to have navicular region pain whereas, all other horses
      were considered to have other cause of palmar heel pain. The responses to various
      diagnostic tests such as hoof tester, distal limb flexion and toe wedge tests
      were compared between the groups. For all diagnostic tests, sensitivity,
      specificity and positive predictive values for navicular pain were calculated.
      According to the present study the single most accurate diagnostic test was
      analgesia of the distal interphalangeal joint for navicular region pain.

PMID- 18819634
TI  - The first host record for Scambus sagax (Hartig, 1838) (Hymenoptera:
      Ichneumonidae) from Turkey.
AB  - Scambus sagax (Hartig) (Hymenoptera: Ichneumonidae) was reared from larvae of
      Agapanthia osmanlis Reiche et Saulcy (Coleoptera: Cerambycidae) in the Bayburt
      province (Kop Mountain Pass). Agapanthia osmanlis is the first known host for
      Scambus sagax in Turkey.

PMID- 18819635
TI  - Urografin in the treatment of sudden sensorineural hearing loss.
AB  - The present study was conducted to find out whether combined treatment of
      intravenous urografin and corticosteroid has a therapeutic advantage over oral
      corticosteroid therapy in the treatment of Sudden Sensorineural Hearing Loss
      (SSNHL). The design of the study was an interventional and controlled clinical
      trial. Between 2003 and 2005, patients with SSNHL were treated in our center in
      Tabriz, Iran. Patients were selected if they had a hearing loss of at least 30 dB
      in at least 3 frequencies on audiometric testing. Audiograms were performed
      before admission, 1 and 2 weeks and 1 and 2 months after treatment. Patients who
      were put on bed rest and received intravenous urografin and hydrocortisone were
      compared with outpatients treated with oral steroid alone. Various descriptive
      analytical calculations and both Chi-square and t-test were used to analyze the
      data. Sixty patients were included in this study. Fifty-one patients referred to
      the otological clinics for the appropriate treatment within the first two weeks
      after the onset of hearing loss. The overall improvement of both groups was
      53.3%. Seventeen (56.6%) of 30 patients treated in the inpatient group who
      received intravenous urografin and intravenous corticosteroid had hearing
      improvement, while half of the outpatient group received oral corticosteroid
      responded positively to the treatment (p > 0.05). This study revealed no
      significant difference in hearing improvement between the hospitalized patients
      who received intravenous urografin and corticosteroid and the patients who
      received oral corticosteroid alone.

PMID- 18819636
TI  - Cholestatic syndromes of infancy.
AB  - This study aimed to provide the analysis of clinical presentation, results of
      laboratory and imaging investigations as well as clinical outcome of children
      with cholestasis. Infants with neonatal cholestasis referred to Children's
      Hospital from 2002 to 2007 were participated in the study in a cross-sectional
      prospective study. Appropriate diagnostic criteria and tests were employed for
      diagnosis the underlying etiologies of neonatal cholestasis. One year mortality
      rate was determined. One hundred twenty one infants, 75 males and 46 females,
      with the mean age of 58.3 +/- 15.3 (14-120) days were enrolled in study. Jaundice
      (94.2%) and hepatomegaly (66.1%) were the most frequent symptom and signs on
      admission. Idiopathic neonatal hepatitis (36.4%), extrahepatic biliary atresia
      (24.8%), metabolic disease (20.7%), intrahepatic ductal paucity (10.7%),
      intrauterine infection (3.3%) were the most frequent causes of neonatal
      cholestasis. One year mortality was 5.8%. There is still not one effective and
      specific diagnostic method in differentiating between the causes of cholestasis
      in the newborns and infants. Some potentially important differences in the
      disease pattern, initial presentation and long-term outcome are suggested from
      the present study when compared to previous reports from other parts of the
      world.

PMID- 18819637
TI  - Evaluation of effect of PxGV-Taiwanii on cabbage moth Plutella xylostella (Lep.:
      Plutellidae) in laboratory conditions.
AB  - The effect of one entomopathogenic virus (PxGV) was studied on cabbage moth
      Plutella xylostella with hope to find management strategies of this insect, based
      on biological control. Bioassay showed that, this virus has high virulence and
      can be considered as the important agents on the control of this insect. The LC50
      value of PxGV for second instar larvae of cabbage moth was calculated 448.58 g
      mm(-2). The LT50 values for the same larvae with 749.89 and 1883.65 g mm(-2)
      doses of PxGV were 6.04 and 6.85 days, respectively.

PMID- 18819638
TI  - In vitro evaluation of Penicillium digitatum Sacc strains sensitivity to various
      fungicides from Jordan.
AB  - This investigation is the first report in Jordan, aimed for in vitro evaluation
      of six fungicides and their combinations, to control the post harvest green mold
      (Penicillium digitatum) of citrus fruits. Thirty one different concentrations
      (0.01-3000 microg mL(-1)) of each fungicide, in addition to 6 combined
      concentrations from each of 7 fungicide mixtures, were tested using Agar well
      diffusion method against four fungal strains. Regression analysis, one way ANOVA
      and Post Hoc Multiple comparisons were carried out to test the significance of
      these treatments. Results of regression analysis indicated significant
      correlation (p < 0.01) between fungicide concentration (microg mL(-1)) and
      inhibition zone (mm) of tested strains. All applied fungicides have resulted in
      complete inhibition of fungal growth in the four tested strains with MIC values
      ranging from 5 to 2700 microg mL(-1). Canvil and Ranvil of the DMI family were
      the most effective against tested strains (except strain dg6) where an MIC in the
      range of 5 to 150 microg mL(-1) was required. Benomyl has worked effectively with
      the least MIC values against the four tested strains. The obtained Benomyl's MIC
      values were: 20, 40, 300 and 40 microg ml(-1) against strains dg2, dg4, dg5 and
      dg6, respectively. One way analysis of variance indicated that the following
      fungicide mixtures: Benomyl/Canvil; Topsin/Vydan; Blin/Canvil; Topsin/Blin and
      Topsin/Canvil had significantly (p < 0.001) affected the sizes of inhibition
      zones, in strains dg2, dg2 and dg5, dg2 and dg4, dg2 and dg4, respectively.
      Scheffe multiple comparisons analysis showed that there were significant
      differences (p < 0.001) between the combined concentrations of 50:50 microg mL(
      1) or 100:100 microg mL(-1) of Benomyl/Canvil mixture and the rest of tested
      concentrations where complete inhibition of growth was achieved at a combination
      of 100:500 microg mL(-1). The mixtures of Benomyl/Canvil and Blin/Canvil were the
      most effective against strains where, wither complete inhibition or the largest
      inhibition zones were obtained at the least (50:50 microg mL(-1)) combined
      concentrations.

PMID- 18819639
TI  - Different irrigation and nitrogen fertilizer treatments on some agro-physiologic
      traits in rapeseed (Brassica napus L.).
AB  - In order to investigate the effect of irrigation and nitrogen fertilizer on
      agronomical and physiological traits of two winter rapeseed varieties, an
      experiment was established in a randomized complete block design as split-plot
      factorial arrangement with four replications in 2005-2006 at Agricultural
      Research Station of Khorramabad, Iran. Irrigation as main-plot factor consisted
      of four levels (I60, I90, I120 and I150). Sub-plot factors included nitrogen in
      four levels (N0, N70, N140, and N210 kg N ha(-1)) and two varieties (Zarfam and
      SLM046). Thousand-seed weight (TSW) in all irrigation and nitrogen levels was
      lower in the 2006 than that of the 2005. Seed oil percentage (SOP) was decreased
      with increasing water use only in second year. As nitrogen rate increased, SOP
      decreased and seed oil yield (SOY) increased in the 2006 significantly (p <
      0.05). With increasing water supply, SOY increased in first year. Zarfam variety
      had a higher TSW and SOP in both years. According to combined analysis results,
      seed and oil yield were not significantly affected by irrigation treatments and
      rapeseed varieties. Seed yield had not significant difference between 70 to 210
      kg N ha(-1) treatments. Both Water Use Efficiency (WUE) and dry matter
      remobilization efficiency (DMRE) were increased by decreasing water supply in I90
      to I150 treatments. But N0 and N210 resulted in the lowest WUE and DMRE,
      respectively. Considering all traits, the first year of experiment was better
      than second year. The irrigation x variety interaction had a significant (p <
      0.01) effect on seed yield and WUE. Generally, I150N70V1 combination is
      recommended in the region of the study due to high performance in production of
      seed and oil yield.

PMID- 18819640
TI  - Colonization and nitrogenase activity of Triticum aestivum (cv. Baccross and
      Mahdavi) to the dual inoculation with Azospirillum brasilense and Rhizobium
      meliloti plus 2,4-D.
AB  - The potential enhancement of root colonization and nitrogenase activity of wheat
      cultivars (Baccross and Mahdavi) was studied with application of two Azospirillum
      brasilense strains (native and Sp7) co-inoculated with two Rhizobium meliloti
      strains (native and DSMZ 30135). The results indicated that the colonization was
      different due to the strains and cultivars of wheat were used. Native A.
      brasilense colonized wheat root better than Sp7 strain. However, Baccross cv.
      reacted better with native Azospirillum compared to Mahdavi cv. which reacted
      better with Sp7. When plants inoculated with dual inoculants (SP7 with standard
      Rhizobium), the colonization of Azospirillum were increased significantly (from
      1.67 x 10(5) to 22 x 10(5) cfu g(-1) FW for Baccras cv. and 3.67 x 10(5) to 26 x
      10(5) cfu g(-1) FW for Mahdavi cultivar). When the standard Rhizobium as co
      inoculants changed to the native Rhizobium, the colonization of Azospirillum was
      higher when compared to the single inoculants but was almost the same when
      compared to the standard Rhizobium. When the standard or native strains of
      Rhizobium used as single inoculation of wheat roots, the number of Rhizobium in
      the wheat roots were not changed significantly. However, when plants co
      inoculated with Rhizobium and Azospirillum, the colonization of Rhizobium was
      increased. Co-inoculation of standard strain of R. melilot with A. brasilense Sp7
      showed that the colonization of Rhizobium were increased from 0.67 x 10(5) to 21
      x 10(5) cfu g(-1) FW for Baccross cv. and 0.33 x 10(5) to 18 x 10(5) cfu g(-1) FW
      for Mahdavi cv. This behavior was the same when inoculation of Rhizobium was
      happened with the native one. In dual inoculation, the highest nitrogenase
      activity was measured in combination of the local strains (native A. brasilense
      with the native R. meliloti) and the lower one belongs to the combination of
      standard strains (Sp7 with standard R. meliloti). The difference in nirtogenase
      activity for different cultivars of wheat with Sp7 and standard Rhizobium is not
      significant but the difference for Sp7 strain plus native Rhizobium is
      significant (p > 0.05). However, the differences were not significant (p < 0.05)
      for nitrogenase activity in bacterial tubes, the difference for nitrogenase
      activity of co-inoculated plants with combination of Sp7 and Rhizobium either
      standard or native were significantly different.

PMID- 18819641
TI  - Bioassay evaluation of the entomopathogenic fungi, Beauveria bassaina Vuellemin
      against eggs and nymphs of Bemisia tabaci Gennadius (Homoptera: Aleyrodidae).
AB  - This study was carried out to determine the lethal effect of the entomopathogenic
      fungi, Beauveria bassaina Vuell. on eggs, young and old nymphs of the whitefly,
      Bemisia tabaci Genn. Mortality percentage was significantly differed based on
      stage of B. tabaci and conidial concentrations of B. bassina. Average of the
      infection level to insect was very low particularly in eggs with only 4.49%, even
      with higher conidial concentrations (6 x 10(6) conidia mL(-1)). Whereas, it was
      higher with 1st and 2nd instars (42.045%) and 3rd and 4th instars (35.93%). Three
      parameters was assessed with B. tabaci eggs, namely; egg infection, egg
      hatchability and crawlers emergence. Egg mortality percentages averaged 1.2, 4.27
      and 8.0% with fungal concentration 2 x 10(6), 4 x 10(6) and 6 x 10(6) conidia mL(
      1), respectively. Daily infection percentages were varied depend upon the
      conidial concentration where the highest infection rate of eggs was occurred with
      6 x 10(6), followed by 4 x 10(6) conidia mL(-1). Egg hatch was very high, while
      the mortality among the emerged crawlers was neglectable compared with the check.
      Efficiency of B. bassaina on whitefly nymphs also was varied based on the insect
      instar and fungal concentration. Mortality percentages were obviously higher to
      young nymphs (1st and 2nd instars) than to older ones (3rd and 4th instars). The
      results indicated that nymphs were highly susceptible to fungal treatment
      compared with eggs. Additionally, pathogenicity and virulence of B. bassaina
      against B. tabaci immatures was not indicated by LC50 only, but also, by the time
      in days (LT50) required to achieve 50% mortality of an insect.

PMID- 18819642
TI  - Simulation study of past climate change effect on chickpea phenology at different
      sowing dates in Gorgan, Iran.
AB  - This simulation study was mainly aimed to find the probable difference between
      sowing dates for response of four chickpea cultivars to past climate change.
      Firstly, the model CYRUS was recoded in QBASIC programming. Then phenology of
      cultivars Jam, Hashem, Arman and Beauvanij, seeded at day of year 50, 70 and 90,
      was evaluated during years 1961 to 2003 in Gorgan, Iran. The changes in some
      climatic variables were also studied. Results revealed that the solar radiation
      has been decreased for month December. Although the value of maximum temperature
      appeared to be the same across years 1961 to 2003 for all months, that of minimum
      temperature tended to show increasing trend for May and August. The increase in
      number of days with temperature higher than 35 degrees C was considerable for
      April and October, but negligible for other months. The warming of night
      temperature was significant only for May and August. It found about 34 mm per 43
      years decrease in monthly rainfall for March. The rate of increase in number of
      days with rainfall was 0.0737 day per year for December. Nearly similar situation
      was found for number of days with rainfall lower than and/or equal to 10 mm. The
      change in number of days with rainfall higher than 10 mm and lower and/or equal
      to 30 mm was in decreasing manner (March, October and December). The length of
      time from sowing to emergence appeared to be constant across past years. The
      advance in flowering (R1) was true only for cultivar Jam seeded at day of year
      70. The length of period from R1 to pod initiation (R3) has been diminished for
      sowing at day of year 70 (Jam and Arman). Only cultivar Hashem seeded at day of
      year 90 tended to have decreasing trend for length of period between R3 and pod
      filling. It found one day (per 43 years) decreases from pod yellowing to maturity
      for cultivar Beauvanij seeded at day of year 70. Based on these findings and on
      the fact that future climate change is predicted using past changes, it seems
      that the adaptation strategies for future, including agronomy and/or breeding
      programs, may be not the same for different sowing dates of chickpea.

PMID- 18819643
TI  - Vasorelaxant and hypotensive effects of Allium cepa peel hydroalcoholic extract
      in rat.
AB  - The aim of present study was to investigate the effect of onion (Allium cepa)
      peel hydroalcoholic extract (OPE) on rat hypertension induced by high-fructose
      diet and aorta contractility. The OPE was prepared by maceration method using 70%
      ethanol. The thoracic aorta from male adult rat (Wistar) was dissected and
      suspended in Krebs-Henseleit solution under 1 g resting tension. Tissue
      preparation was contracted by KCl (80 mM) or phenylephrine (Phe, 1 microM) and
      then the extract was applied cumulatively (0.0625-2 mg mL(-1)). Hypertension was
      induced in negative control and three groups of rats by adding fructose (10%
      WN/V) in drinking water for 6 weeks but control group received tap water.
      Hypertensive groups received saline or OPE at 200, 400 and 800 mg kg(-1) daily
      for last 3 weeks by gavage. Results showed that OPE reduces aorta contractions
      induced by KCl or Phe in a concentration-dependent manner (p < 0.001). Removing
      aorta endothelium did not attenuate the OPE activity. Inhibition of nitric oxide,
      cGMP and prostaglandin synthesis by L-NAME (100 microM), methylene blue (10
      microM) and indomethacin (10 microM), respectively, did not attenuate OPE
      activity. Atropine abolished ACh-induced relaxation in Phe precontracted aorta
      but not the OPE-induced relaxation. Although the extract did not change heart
      rate but after 3 weeks reduced the hypertension induced by fructose (p < 0.001).
      Present results indicated that OPE reduces aortic contractions possibly via
      inhibition of calcium influx but without involving NO, cGMP, endothelium and
      prostaglandins. The OPE hypotensive effect could be due to extract quercetin
      content, antioxidant activity and inhibiting vascular smooth muscle cells Ca2+
      influx.

PMID- 18819644
TI  - Inheritance characteristics of F1 and F2 offsprings obtained from full diallele
      crosses of five cowpea cultivars (Vigna unguiculata L. Walp) against
      pseudocercospora leaf spot disease.
AB  - The experiment was carried out at the Experimental Farm, Department of
      Agricultural Technology, Mahasarakham University, Mahasarakham Province in the
      2005 (February to April) for F1 offsprings and also at the Experimental Farm,
      Khon Kaen University, Khon Kaen Province, Northeast Thailand for F2 offsprings
      (July to October), i.e., four experiments were carried out, each location had two
      experiments. The research aimed to investigate inheritance characteristics of F1
      and F2 offsprings derived from full diallele crosses of five cowpea cultivars (20
      pairs of crosses) against a pathogenic disease of Pseudocercospora cruenta
      (Sacc,) Deighton. The first two experiments were carried out under field and
      glasshouse conditions at Mahasarakham University for F1 offsprings and the other
      two experiments were carried out at Khon Kaen University for F2 offsprings. A Chi
      square test method was used to justify dominant genes on the infection of the
      disease. The results showed that the cowpea plants of F1 and F2 offsprings gave
      only one pair of dominant gene that had its complete dominant effect over
      recessive gene of the cowpea offsprings.

PMID- 18819645
TI  - Effects of niacin on milk production and blood parameters in early lactation of
      dairy cows.
AB  - To investigate the effects of niacin supplementation in the diet of high
      producing cows at early lactation, 21 holstein dairy cows were used in this
      experiment. Animal were assigned in to three groups based on their milk yield and
      calving date soon after parturition. They were received a basal diet and 0 (group
      1), 6 (group 2), 12 (group 3) g of supplementation niacin per day over a 10 weeks
      experimental period. Milk volume was recorded and milk samples were collected for
      each cow at two weeks interval for analysis of fat, protein, lactose and SNF
      (Solid-None Fat). Blood samples were also taken for the measurement of glucose,
      triglyceride, Beta-hydroxy butyrate and total protein at two weeks intervals. No
      significant difference were observed between milk yield, milk fat, protein,
      lactose and SNF content in cows received niacin compared to the control group (p
      > 0.05). Plasma glucose in groups 2 and 3 compared to the control were higher and
      this difference were statistically significant (p < 0.05). Blood triglycerides
      were not significantly affected by niacin supplementation. BHBA were lower in
      cows received niacin and this difference were significant (p < 0.05). The trend
      of changes in the amount of blood total protein were identical in all three
      groups whole the level of this factor was always higher in control group compared
      to the others groups. Niacin has showed an increase in the level of plasma
      glucose and a notable decrease in the amount of blood triglyceride, beta-hydroxy
      butyrate and total protein, which may be due to the effect of this vitamin on the
      energy metabolism in cows.

PMID- 18819646
TI  - Acclimated biomass that degrades Sulfonated Naphthalene Formaldehyde Condensate.
AB  - A number of aerobic species were isolated from textile industry activated sludge
      wastewater. The bacterial consortium was acclimated during seven days before
      testing its capacity of Sulfonated Naphthalene-Formaldehyde Condensate (SNFC)
      recalcitrant compound degradation. SNFC's degradation was evaluated by using
      different techniques including: vapour pressure osmometry, spectroscopy UV
      Visible and Chemical Oxygen Demand (COD). The degradation of SNFC by acclimated
      bacterial consortium was determined by monitoring the decrease of absorbance and
      of COD at wavelength 288 nm. We were able to deduce that biodegradation of SNFC
      involves two steps: cleavage of CH2 bridges and the degradation of the aromatic
      nuclei. The bacteria species community that was able to degrade SNFC consisted of
      aerobic Gram-negative rods belonging to the Pseudomonadaceae family. The strains
      were identified as Bukholderia cepacia, Brevundimonas vesicularis, Pseudomonas
      stutzeri, Ralostonia picketti, Shewanella putrefaciens, Sphingomonas paucimobilis
      and Agrobacterium radiobacter.

PMID- 18819647
TI  - Ileal relaxation induced by Mentha longifolia (L.) leaf extract in rat.
AB  - The effect of Mentha longifolia (L.) leaf hydroalcoholic extract (MLE) was
      examined on rat ileal smooth muscle contractions. Last portion of ileum from male
      adult Wistar rat was mounted in an organ bath containing Tyrode solution. The
      tissue was contracted by carbachol (CCh, 10 microM), KCl (60 mM) and BaC12 (4 mM)
      and then MLE (0.0625-1 mg mL(-1)) was added to the bath cumulatively. The effect
      of MLE on KCl-induced contraction was examined after tissue incubation with
      propranolol (1 microM), naloxone (1 microM) and N omega-nitro-L-arginine methyl
      ester (L-NAME, 100 microM). The effect of MLE on CaCl2-induced ileal contraction
      in Ca(2+)-free with high potassium Tyrode solution was also evaluated. The role
      of potassium channels was examined by ileum incubation (5 mim) with
      tetraethylammonium (TEA, 1 mM). The results showed that KCl-, CCh and BaCl2
      induced ileal contractions were inhibited (p < 0.001) by cumulative
      concentrations of MLE with the same potency. In addition, MLE (0.25-1 mg mL(-1))
      inhibited (p < 0.01) ileal contractions induced by CaCl2 (0.45-2.7 mM) in a
      concentration-related manner. The antispasmodic effect of MLE was affected
      neither by propranolol, L-NAME nor by naloxone. The MLE concentration-response
      curve was shifted to the right (p < 0.05) by tissue incubation with TEA. From
      results it may be suggested that Mentha longifolia hydroalcoholic leaf extract
      induces its spasmolytic activity mainly through disturbance in calcium
      mobilization and partly by potassium channels activation. Present results show
      that Mentha longifolia leaf extract exerts relaxant effects on intestinal smooth
      muscle, consistent with the traditional use of the plant to treat
      gastrointestinal disorders such as diarrhea and colic.

PMID- 18819648
TI  - Antioxidant properties of peel and pulp hydro extract in ten Persian pomegranate
      cultivars.
AB  - This study compares the antioxidant activity of ten different pomegranate
      cultivars grown in Iran using the ferric reducing power assay (FRAP assay), which
      is based on the reduction of a ferric-tripyridyl triazine complex to its ferrous,
      colored form in the presence of antioxidants. Aqueous solutions of known Fe(+2)
      concentration, in the range of 100-1000 micromol L(-1) were used for calibration.
      The results showed that among pulp and peel fractions the sour alac and sweet
      white peel cultivars had more FRAP value respectively. The pomegranate peel
      extract had markedly higher antioxidant capacity than the pulp extract. The peel
      extract of sweet white peel cultivar appeared to have more potential as a health
      supplement rich in natural antioxidants compared to the pulp and peel extracts of
      other pomegranate cultivars.

PMID- 18819649
TI  - Prevalence of mental disorders among shift work hospital nurses in Shiraz, Iran.
AB  - The present study was conducted to determine the prevalence of mental disorders
      among shift work hospital nurses in Shiraz. One thousand one hundred and ninety
      five nurses from 12 general hospitals were investigated by Persian version of
      General Health Questionnaire-28 (GHQ-28) as screen tool. Using a checklist,
      structured observations were made to assess working environment. Selecting a
      score of 6 in GHQ-28 as cut-off point, 45.4% of nurses were found to suffer from
      mental disorders and this was more common among females. Similarly, anxiety and
      somatic symptoms were more prevalent than other types of mental disorders (43.2
      and 34.5%, respectively). The prevalence of depression and social dysfunction
      were 11.2 and 79.5%, respectively. Shift work was significantly associated with
      anxiety (p < 0.05). Likewise, marital status was significantly associated with
      depression and social dysfunction (p < 0.001). It was concluded that the mental
      health pattern in hospital nurses was similar to that of general Iranian
      population as the referent population. However, the prevalence rates of social
      dysfunction, somatisation and anxiety symptoms among the nurses were higher than
      the referent population.

PMID- 18819650
TI  - Screening of sugar beet tissue culture clones for resistance to rhizomania
      disease.
AB  - In this study, sugar beet tissue culture clones were used to screen rhizomania
      resistant genotypes. At first, explants derived from shoot tips of sugar beet
      seedlings were transferred to shoot tip elongation media after surface
      sterilization. Then, the grown shoots were transferred to media containing
      various hormonal combinations NAA, BA, IBA and GA3 for multiplication, growth and
      rooting. Later, the clones were transferred to soil-peatmoss mixture were adapted
      to greenhouse conditions. For screening clones against rhizomania, the genotypes
      of adapted clones were selected and inoculated to rhizomania-infested soil. This
      experiment was in a randomized complete block design with three replicates (three
      inoculation times) in greenhouse. Adapted plants were transferred to the soil
      containing rhizomania virus. All infested soils were diluted 3 to 7 with sand.
      After two months, infested plants were examined by DAS-ELISA test also optical
      densities of the samples were analyzed by SAS program. Significant differences
      among genotypes and blocks were observed. Genotypes were classified to few groups
      (ranked from completely susceptible to completely resistant). The difference
      between blocks was because of difference of inoculation time temperature. Use of
      clones of each genotype caused an increase in selection accuracy of resistant
      genotypes. By use of this method, chance of escaping from inoculation factor
      decrease and researchers can determine to be resistance of plants with high level
      of confidence and apply in breeding programs.

PMID- 18819651
TI  - Variation in testicular histology of the spiny tailed lizard Uromastyx aegyptius
      microlepis during hibernation and active periods.
AB  - The testicular histology of the lizard, Uromastyx aegyptius microlepis were
      varied considerably during hibernation and activity periods, reaching maximum
      values in summer. The onset of winter induces testicular regression, reduced
      testis size, testis diameter, diameter and epithelial height of the seminiferous
      tubules and epididymal epithelial height. Animals exhibit testicular
      recrudescence during late winter (February and March) and maximum testicular
      volume occurred during June. The period of maximal testicular volume was
      positively correlated with increasing ambient temperature. The summer season
      induces the testicular activity in contrast with the winter season in which the
      activity decreased and the testes were collapsed. Spermatocytogenesis is active
      in early spring and the major portion of the seminiferous epithelium comprises
      spermatids in various stages of maturation and their luminae were filled with
      spermatozoa. The size of the interstitial cells is direct correlated with changes
      occurring in epididymis and seminiferous epithelium. Most interstitial cell
      nuclei show clear regression when spermatocytogenesis were diminishes.

PMID- 18819652
TI  - Incidence of human malaria infection in northern hilly region of Balochistan,
      adjoining with NWFP, Pakistan: district Zhob.
AB  - This study was conducted to investigate the incidence of malarial infections in
      human population in 37 localities of district Zhob, Balochistan, Pakistan.
      Malarial parasites were identified in the blood slides of suspected patients of
      the disease from July, 2004 to June, 2006 and encompassed 7748 subjects. Out of
      7748 suspected cases of malaria, 3240 (41.8%) were found to be positive for
      malarial parasite in blood smear slides. Out of positive cases, 1681 (51.8%) were
      identified as Plasmodium vivax infection and 1559 (48.1%) cases with P.
      falciparum. However, seasonal variation was also noted with the highest (85.4%:
      141/165) infection of P. vivax in March and lowest (18.6%: 59/316) in October
      while infection of P. falciparum was highest (81.3%: 257/316) in October and
      lowest (14.5%: 24/165) in March. Infection with P. vivax in male was 75.7%
      (125/165) in March and in female 26.3% (58/220) in May whereas infection of P.
      falciparum in male was 61.5% (245/398) in July and in female was 20.5% (65/316)
      in October. These results are compared with those of other studies done in
      Pakistan. Cases of P. malariae and P. ovale were not found in the present study.
      In conclusion it can be pointed out that the high incidence rate of P. vivax
      (51.8%:1681/3240) in Zhob district poses a significant health hazard because it
      may also lead to cerebral malaria as it was suggested by previous workers.

PMID- 18819653
TI  - Effects of a locally produced blood meal on performance, carcass traits and
      nitrogen retention of broiler chickens.
AB  - The study was designed as a 2 x 5 factorial arrangement with main effects of
      feeding blood meal as a replacement of 0, 25, 50, 75 or 100% of dietary fish meal
      and the duration of this substitution at 1-42 or 21-42 days of age. One thousand
      1 day old male Cobb 500 broiler chicks assigned randomly to each of 40 floor pens
      (25 birds/pen) and were fed five isonitrogenous and isocaloric feeds formulated
      to contain 20.38 and 17% crude protein and 2900 and 3000 kcal kg(-1)
      metabolizable for starter and grower periods, respectively. Duration of dietary
      manipulation didn't affect the measured parameters. More than 25% blood meal/fish
      meal substitution ratios significantly increased chickens daily weight gain and
      decreased the cost of producing a unit of meat. Other traits didn't affect by
      dietary fish meal/blood meal replacement ratio. Spleen and proventriculus
      percents and small intestine length affected by level of replacement but didn't
      follow a distinct pattern. These results indicate that this locally produced
      blood meal is a suitable substitute for dietary fish meal and a full replacement
      didn't cause any adverse effect on performance, carcass important traits and
      dietary nitrogen retention of broiler chickens.

PMID- 18819654
TI  - Microscopic evaluation of renal changes in experimental canine visceral
      leishmaniosis after chemo- and immunotherapy.
AB  - Visceral Leishmania (VL) with diverse clinical manifestation is prevalent and
      remains a major public health problem in Iran. This study was performed in Ahwaz,
      Khozestan province southwest to increase immune system and to reduce of the renal
      lesions. Treatment of dogs with visceral leishmaniosis is basically the same as
      the treatment of human. However, cure is not usually achieved, leaving the
      sacrifice of animal as the only feasible choice. The goal of this work was to
      test the therapeutic efficacy of N-methyl glutamic antimoate (glucnime),
      Mycobacterium vaccae adjuvant (SRL 172), alone and in association with L. major
      promastigote and the latter compound in association to glucantime, in dog with
      visceral leishmaniasis. In this trial 18, mixed bred dogs with different ages,
      receiving amastigte promastigote of L. infantum intravenously were used. They
      were monitored for 6 months. Serologic assays (Elisa, Dot and IFAT) were
      performed on blood samples of each animal. The animals were divided into six
      groups, each having 3 dogs: Group 1: receiving 100 mg kg(-1) day(-1) Glucantime
      for 30 days, IM. Group 2: Receiving 3 mg dog(-1) (0.1 mL) of Mycobacterium vaccae
      adjuvant suspension intradermaly. Group 3: receiving L. major promastigote plus
      M. vaccae adjuvant each of them 0.1 mL intradermaly by one month intervals for 3
      months. Group 4: receiving Glucantime in association L. major promastigote plus
      M. vaccae adjuvant with previous doses. Group 5: Receiving no treatment. Group 6:
      was control group with no infection and treatment. In microscopic evaluation
      following lesions have been shown in kidney: Chronic, interstitial nephritis,
      sever glomerulosclerosis, membranoproliferative glomerulonephritis and also non
      suppurative nephritis were the lesions in 5 groups. The prescription of
      Mycobacterium vaccae adjurant was able to reduce the number of parasites in the
      macrophages of liver and spleen in this round of treatment.

PMID- 18819655
TI  - Bioremediation of engine oil polluted soil by the tropical white rot fungus,
      Lentinus squarrosulus Mont. (Singer).
AB  - This study was conducted to test the efficacy of an indigenous white rot fungus
      Lentinus squarrosulus in degrading engine oil in soil. Flasks containing
      sterilized garden soil (100 g) moistened with 75% distilled water (w/v) were
      contaminated with engine oil 1, 2.5, 5, 10, 20 and 40% w/w concentrations,
      inoculated with L. squarrosulus and incubated at room temperature for 90 days.
      Levels of organic matter, pH, total hydrocarbon and elemental content (C, Cu, Fe,
      K, N, Ni, Zn and available P) were determined post-fungal treatment. Results
      indicate that contaminated soils inoculated with L. squarrosulus had increased
      organic matter, carbon and available phosphorus, while the nitrogen and available
      potassium was reduced. A relatively high percentage degradation of Total
      Petroleum Hydrocarbon (TPH) was observed at 1% engine oil concentration (94.46%),
      which decreased to 64.05% TPH degradation at 40% engine oil contaminated soil
      after 90 days of incubation. The concentrations of Fe, Cu, Zn and Ni recovered
      from straw/fungal biomass complex increased with the increase of engine-oil
      contamination and bio-accumulation by the white-rot fungus. The improvement of
      nutrient content values as well as the bioaccumulation of heavy metals at all
      levels of engine oil concentrations tested through inoculations with L.
      squarrosulus is of importance for the bioremediation of engine-oil polluted
      soils.

PMID- 18819656
TI  - The influence of different hormone concentration and combination on callus
      induction and regeneration of Rauwolfia serpentina L. Benth.
AB  - The influence of media composition on callus induction and subsequent
      regeneration of Rauwolfia serpentina L. Benth has been studied. High frequency
      (96.43%) callus induction was obtained when nodal segments from in vitro raised
      shoots were cultured on MS medium supplemented with 0.5 mg L(-1) BA and 2.0 mg L(
      1) NAA. The callus differentiated into adventitious shoots when it was
      subcultured on MS medium supplemented with 2.0 mg L(-1) BA with 0.2 mg L(-1) NAA.
      Regenerated shoots were best rooted on half-strength MS medium with 1.0 mg L(-1)
      each of IBA and IAA.

PMID- 18819657
TI  - Molecular detection of potato spindle tuber viroid in Razavi and Northern
      Khorasan provinces.
AB  - The aim of this study was to identify the Potato Spindle Tuber Viroid (PSTVd) by
      Reverse Transcriptase-PCR. Among all plant diseases which are caused by viroids,
      PSTVd was the first viroid which is recognized by plant pathologist. Suspended
      potato tubers from Razavi and Northern Khorasan provinces collected and cultured.
      Leaves of cultured tubers were used for RNA extraction by PEG6000 Precipitation
      method. Subsequent RT-PCR reaction has been carried out using specific primers. A
      359 bp fragment has been appeared after electrophoresis which has not appeared in
      healthy tuber samples. Digestion of obtained fragment with BamHI confirmed the
      sequence by producing two fragments of 119 and 240 bp. Sequencing has been done
      to certify the PSTVd. The sequencing result showed that infection in tested areas
      is caused by mild strain of PSTVd. In this project from 250 samples, 14 tubers
      were infected. This was the first report of occurrence of mild strain of PSTVd in
      Iran.

PMID- 18819658
TI  - Antioxidant status of bilirubin and uric acid in patients diagnosed with
      Plasmodium falciparum malaria in Douala.
AB  - Oxidative stress and changes in antioxidant status have been implicated in the
      pathogenesis of malaria. To assess the antioxidant level ofbilirubin and uric
      acid associated with falciparum malaria infection, 60 untreated patients (30 men
      and 30 women) in Douala, Cameroon were screened for the study. Sixty five healthy
      individuals (29 men and 36 women) were used as controls. Total and conjugated
      bilirubin were calculated using Jendrassik-Grof method while uric acid was
      determined using Barham-Trinder method. It was observed that total and conjugated
      bilirubins were significantly (p < 0.001) higher in malaria patients (10.722 +/-
      4.043 and 3.627 +/- 1.571 mg L(-1), respectively) when compared to control (6.830
      +/- 2.436 and 1.777 +/- 0.729 mg L(-1)) and these bilirubin levels increased
      significantly with parasite count (p < 0.050). There was also significant
      increased (p = 0.021) of uric acid in malaria patients (56.262 +/- 13.963 mg L(
      1)) compared to controls (49.838 +/- 15.419 mg L(-1)). No significant differences
      based on sex were observed on uric acid, parasite count, total and conjugated
      bilirubins in malaria patients. Positive correlations were obtained between
      parasite count and total bilirubin (r = 0.320, p < 0.050), conjugated bilirubin
      (r = 0.477, p < 0.001), uric acid (r = 0.060, p > 0.050) and between total and
      conjugated bilirubin (r = 0.729, p < 0.001). From this study, it has been
      hypothesized that the augmentation of plasma level ofbilirubin and uric acid
      could provide more protection against oxidative stress induced by malaria.

PMID- 18819659
TI  - Climate change: impact on the epidemiology and control of animal diseases.
      Preface.

PMID- 18819660
TI  - Climate change: impact on the epidemiology and control of animal diseases.
      Introduction.

PMID- 18819661
TI  - The origin of climate changes.
AB  - Investigation on climate change is coordinated by the Intergovernmental Panel on
      Climate Change (IPCC), which has the delicate task of collecting recent knowledge
      on climate change and the related impacts of the observed changes, and then
      developing a consensus statement from these findings. The IPCC's last review,
      published at the end of 2007, summarised major findings on the present climate
      situation. The observations show a clear increase in the temperature of the
      Earth's surface and the oceans, a reduction in the land snow cover, and melting
      of the sea ice and glaciers. Numerical modelling combined with statistical
      analysis has shown that this warming trend is very likely the signature of
      increasing emissions of greenhouse gases linked with human activities. Given the
      continuing social and economic development around the world, the IPCC emission
      scenarios forecast an increasing greenhouse effect, at least until 2050 according
      to the most optimistic models. The model ensemble predicts a rising temperature
      that will reach dangerous levels for the biosphere and ecosystems within this
      century. Hydrological systems and the potential significant impacts of these
      systems on the environment are also discussed. Facing this challenging future,
      societies must take measures to reduce emissions and work on adapting to an
      inexorably changing environment. Present knowledge is sufficientto start taking
      action, but a stronger foundation is needed to ensure that pertinent long-term
      choices are made that will meet the demands of an interactive and rapidly
      evolving world.

PMID- 18819662
TI  - Predicted climate changes for the years to come and implications for disease
      impact studies.
AB  - The paper presents a review of the current ability of the climate modelling
      community to produce predictions of future climate change. Predictions for the
      next few decades are reasonably robust, whereas predictions for later time
      periods depend on uncertainties in climate model structure and on the unknown
      future course of greenhouse gas emissions. Some regional features are noticeable;
      however, meaningful interpretation of these can only presently be made at spatial
      scales that are considerably larger than those required for making sound
      estimates of the effects of future climate change on animal health. The
      implication is that current climate change predictions should be considered
      indicative rather than accurate.

PMID- 18819663
TI  - Climate change and biodiversity.
AB  - There is already widespread change in the natural calendars (phenology) of plants
      and animals, as well as change in some species distributions. Now threshold
      change (sudden, fundamental change) in ecosystems is beginning to be observed in
      nature. At minimum, the natural world will experience an equal amount of warming
      to that which has already taken place. This all suggests a future with nature and
      ecosystems very much in flux with profound implications for epidemiology.

PMID- 18819664
TI  - Climate change: effects on animal disease systems and implications for
      surveillance and control.
AB  - Climate driven and other changes in landscape structure and texture, plus more
      general factors, may create favourable ecological niches for emerging diseases.
      Abiotic factors impact on vectors, reservoirs and pathogen bionomics and their
      ability to establish in new ecosystems. Changes in climatic patterns and in
      seasonal conditions may affect disease behaviour in terms of spread pattern,
      diffusion range, amplification and persistence in novel habitats. Pathogen
      invasion may result in the emergence of novel disease complexes, presenting major
      challenges for the sustainability of future animal agriculture at the global
      level. In this paper, some of the ecological mechanisms underlying the impact of
      climatic change on disease transmission and disease spread are further described.
      Potential effects of different climatic variables on pathogens and host
      population dynamics and distribution are complex to assess, and different
      approaches are used to describe the underlying epidemiological processes and the
      availability of ecological niches for pathogens and vectors. The invasion process
      can disrupt the long-term co-evolution of species. Pathogens adhering to an r
      type strategy (e.g. RNA viruses) may be more inclined to encroach on a novel
      niche resulting from climate change. However, even when linkage between disease
      dynamics and climate change are relatively strong, there are other factors
      changing disease behaviour, and these should be accounted for as well. Overall
      vulnerability of a given ecosystem is a key variable in this regard. The impact
      of climate-driven changes varies in different parts of the world and in the
      different agro-climatic zones. Perhaps priority should go to those geographical
      areas where the integrity of the ecosystem is most severely affected and the
      adaptability, in terms of robustness and sustainability of response, relatively
      low.

PMID- 18819665
TI  - How the biodiversity sciences may aid biological tools and ecological engineering
      to assess the impact of climatic changes.
AB  - This paper addresses how climate changes interact with other global changes
      caused by humans (habitat fragmentation, changes in land use, bioinvasions) to
      affect biodiversity. Changes in biodiversity at all levels (genetic, population
      and community) affect the functioning of ecosystems, in particular host-pathogen
      interactions, with major consequences in health ecology (emergence and re
      emergence; the evolution of virulence and resistance). In this paper, the authors
      demonstrate that the biodiversity sciences, epidemiological theory and
      evolutionary ecology are indispensable in assessing the impact of climate
      changes, and also for modelling the evolution of host-pathogen interactions in a
      changing environment. The next step is to apply health ecology to the science of
      ecological engineering.

PMID- 18819666
TI  - Dynamics of tick-borne disease systems: minor role of recent climate change.
AB  - Tick-borne disease systems are very sensitive to climate through the impact of
      temperature and moisture stress on rates of the demographic processes of ticks.
      There is no a priori reason, however, to expect tick abundance or seasonal
      activity patterns to respond to climate change in ways that inevitably increase
      the risk of infection by the transmitted pathogens. Changing host availability
      may be more important than climate in determining tick abundance. The credibility
      of any (inherently untestable) predictions of future system-specific changes will
      be strengthened if based on satisfactory explanations of the past. Tick-borne
      encephalitis (TBE) in Europe is presented as a case study: observed patterns of
      climate change are too similar within and between countries to provide the sole
      explanation for the extreme spatio-temporal heterogeneity of the marked upsurges
      in TBE incidence over the past two decades. Instead, a nexus of interacting
      factors affecting both the risk of infection and exposure of humans to that risk,
      and each differing in force in space and time, is a more powerful model. Many of
      these factors are driven by socio-economic changes, and include climate, land
      cover, wildlife, agricultural practices, industrial activities, (un)employment
      and income. The same principle may apply to the periodic epidemics of Crimean
      Congo haemorrhagic fever.

PMID- 18819667
TI  - Climate change and mosquito-borne disease: knowing the horse before hitching the
      cart.
AB  - Speculations on the potential impacts of climate change on human health often
      focus on the mosquito-borne diseases but ignore the complex interplay of the
      multitude of factors that are generally dominant in the dynamics of their
      transmission. A holistic view of this complexity - particularly the ecology and
      behaviour of the host and the ecology and behaviour of the vector - is the only
      valid starting point for assessing the significance of climate in the prevalence
      and incidence of these diseases.

PMID- 18819668
TI  - Leishmaniasis emergence and climate change.
AB  - Spatio-temporal modelling of the distributions of the leishmaniases and their
      sandfly vectors is reviewed in relation to climate change. Many leishmaniases are
      rural zoonoses, and so there is a foundation of descriptive ecology and
      qualitative risk assessment. Dogs are widespread reservoir hosts of veterinary
      importance. Recent statistical modelling has not always produced novel general
      conclusions, exemplifying the difficulty of applying models outside the original
      geographical region. Case studies are given for transmission cycles involving
      both cutaneous and visceral leishmaniasis in the Old World and the Americas. An
      important challenge is to integrate statistical spatial models based mainly on
      climate with more explanatory biological models. Ecological niche models pose
      difficulties because of the number of assumptions. A positive association has
      been reported between the El Nino cycle and the annual incidence of visceral
      leishmaniasis in Brazil, but more basic research is needed before tackling other
      climate-change scenarios, including leishmaniasis emergence in northern Europe.

PMID- 18819669
TI  - The impact of climate change on the epidemiology and control of Rift Valley
      fever.
AB  - Climate change is likely to change the frequency of extreme weather events, such
      as tropical cyclones, floods, droughts and hurricanes, and may destabilise and
      weaken the ecosystem services upon which human society depends. Climate change is
      also expected to affect animal, human and plant health via indirect pathways: it
      is likely that the geography of infectious diseases and pests will be altered,
      including the distribution of vector-borne diseases, such as Rift Valley fever,
      yellow fever, malaria and dengue, which are highly sensitive to climatic
      conditions. Extreme weather events might then create the necessary conditions for
      Rift Valley fever to expand its geographical range northwards and cross the
      Mediterranean and Arabian seas, with an unexpected impact on the animal and human
      health of newly affected countries. Strengthening global, regional and national
      early warning systems is crucial, as are co-ordinated research programmes and
      subsequent prevention and intervention measures.

PMID- 18819670
TI  - Invasion of bluetongue and other orbivirus infections into Europe: the role of
      biological and climatic processes.
AB  - The invasion of multiple strains of the midge-borne bluetongue virus into
      southern Europe since the late 1990s provides a rare example of a clear impact of
      climate change on a vector-borne disease. However, the subsequent dramatic
      continent-wide spread and burden of this disease has depended largely on altered
      biotic interactions with vector and host communities in newly invaded areas.
      Transmission by Palearctic vectors has facilitated the establishment of the
      disease in cooler and wetter areas of both northern and southern Europe. This
      paper discusses the important biological and climatic processes involved in these
      invasions, and the lessons that must be drawn for effective risk management of
      bluetongue and other midge-borne viruses in Europe.

PMID- 18819671
TI  - Effects of climate change on animal and zoonotic helminthiases.
AB  - Current knowledge of animal and zoonotic helminthiases in which effects of
      climate change have been detected is reviewed. Climate variables are able to
      affect the prevalence, intensity and geographical distribution of helminths,
      directly influencing free-living larval stages and indirectly influencing mainly
      invertebrate, but also vertebrate, hosts. The impact of climate change appears to
      be more pronounced in trematodes, and is mainly shown by increased cercarial
      production and emergence associated with global warming. Fascioliasis,
      schistosomiasis (S. japonicum) and cercarial dermatitis caused by avian
      schistosomes have been the focus of study. Alveolar echinococcosis is currently
      the only cestode disease that climate change has been found to influence.
      Nematodiases, including heterakiasis, different trichostrongyliases and
      protostrongyliases, ancylostomiases and dirofilariases, are the helminth diseases
      most intensively analysed with regard to climate change. It may be concluded that
      helminth diseases should be listed among the infectious diseases with which
      special care should be taken because of climate change in the future, especially
      in temperate and colder northern latitudes and in areas of high altitude.

PMID- 18819672
TI  - Climate change and avian influenza.
AB  - This paper discusses impacts of climate change on the ecology of avian influenza
      viruses (AI viruses), which presumably co-evolved with migratory water birds,
      with virus also persisting outside the host in subarctic water bodies. Climate
      change would almost certainly alter bird migration, influence the AI virus
      transmission cycle and directly affect virus survival outside the host. The
      joint, net effects of these changes are rather unpredictable, but it is likely
      that AI virus circulation in water bird populations will continue with endless
      adaptation and evolution. In domestic poultry, too little is known about the
      direct effect of environmental factors on highly pathogenic avian influenza
      transmission and persistence to allow inference about the possible effect of
      climate change. However, possible indirect links through changes in the
      distribution of duck-crop farming are discussed.

PMID- 18819673
TI  - The impact of climate change on the parasites and infectious diseases of aquatic
      animals.
AB  - Climate change is predicted to have important effects on parasitism and disease
      in freshwater and marine ecosystems, with consequences for human health and socio
      economics. The distribution of parasites and pathogens will be directly affected
      by global warming, but also indirectly, through effects on host range and
      abundance. To date, numerous disease outbreaks, especially in marine organisms,
      have been associated with climatic events such as the El Nino-Southern
      Oscillation. In general, transmission rates of parasites and pathogens are
      expected to increase with increasing temperature. Evidence suggests that the
      virulence of some pathogens and parasites may also increase with global warming.
      The effects of climate change on parasites and pathogens will be superimposed
      onto the effects of other anthropogenic stressors in ecosystems, such as
      contaminants, habitat loss and species introductions. This combination of
      stressors may work cumulatively or synergistically to exacerbate negative effects
      on host organisms and populations. Climatic effects on parasites and diseases of
      key species may cascade through food webs, with consequences for entire
      ecosystems.

PMID- 18819674
TI  - Climate change: impact on honey bee populations and diseases.
AB  - The European honey bee, Apis mellifera, is the most economically valuable
      pollinator of agricultural crops worldwide. Bees are also crucial in maintaining
      biodiversity by pollinating numerous plant species whose fertilisation requires
      an obligatory pollinator. Apis mellifera is a species that has shown great
      adaptive potential, as it is found almost everywhere in the world and in highly
      diverse climates. In a context of climate change, the variability of the honey
      bee's life-history traits as regards temperature and the environment shows that
      the species possesses such plasticity and genetic variability that this could
      give rise to the selection of development cycles suited to new environmental
      conditions. Although we do not know the precise impact of potential environmental
      changes on honey bees as a result of climate change, there is a large body of
      data at our disposal indicating that environmental changes have a direct
      influence on honey bee development. In this article, the authors examine the
      potential impact of climate change on honey bee behaviour, physiology and
      distribution, as well as on the evolution of the honey bee's interaction with
      diseases. Conservation measures will be needed to prevent the loss of this rich
      genetic diversity of honey bees and to preserve ecotypes that are so valuable for
      world biodiversity.

PMID- 18819675
TI  - Pathogens of domestic and free-ranging ungulates: global climate change in
      temperate to boreal latitudes across North America.
AB  - In North America broad-based research networks explore the interaction of
      vertebrates, their characteristic arrays of pathogens and emergent disease. A
      diversity of programmes address the impact of environmental change on animal
      health, zoonoses, and human health, but as yet no comprehensive framework or
      strategy has emerged to develop and implement policy and planning. In a regime of
      climate change and ecological perturbation, the need to document and understand
      the health, agricultural, societal and economic impact of pathogens and emerging
      infectious disease is urgent. An integrated and proactive planning process
      linking national and international resources can lead to informed predictions
      aboutthe impact of environmental change and can identify pathways for potential
      management and mitigation. An effective and comprehensive programme will have
      components for establishing priorities, developing primary data for faunal
      structure and biodiversity, a capacity for monitoring and surveillance (including
      scanning and targeted activities), and linkage to historical and contemporary
      baselines (against which to assess change) established through archival
      biological collections. Field and laboratory studies are also necessary to
      determine developmental thresholds, tolerances and tipping points for many
      pathogens to establish a context for recognising current constraints and future
      perturbation, and to explore factors that promote emergence for a variety of
      pathogens, vectors and pest species. Predictive modelling and risk assessment
      utilising a range of scenarios for climate change is a final step in this
      multidisciplinary process.

PMID- 18819676
TI  - Global change: impact, management, risk approach and health measures--the case of
      Europe.
AB  - Global changes, including an increase in trade and global warming, which act on
      the environment, are likely to impact on the evolution of pathogens and hence of
      diseases. To anticipate the risks created by this new situation, a French group
      of experts has developed a method for prioritising animal health risks. This is a
      two-phase method: the first step is to identify the diseases whose incidence or
      geographical distribution could be affected by the changes taking place, and the
      second step is to evaluate the risk of each of these diseases. As a result of
      this process, six priority diseases were selected: bluetongue, Rift Valley fever,
      West Nile fever, visceral leishmaniasis, leptospirosis and African horse
      sickness. The main recommendations were: to develop epidemiological surveillance,
      to increase knowledge of epidemiological cycles, to develop research into these
      diseases and to pool cross-border efforts to control them.

PMID- 18819677
TI  - Climate change and animal health in Africa.
AB  - Climate change is expected to have direct and indirect impacts on African
      livestock. Direct impacts include increased ambient temperature, floods and
      droughts. Indirect impacts are the result of reduced availability of water and
      forage and changes in the environment that promote the spread of contagious
      diseases through increased contact between animals, or increased survival or
      availability of the agent or its intermediate host. The distribution and
      prevalence of vector-borne diseases may be the most significant effect of climate
      change. The potential vulnerability of the livestock industry will depend on its
      ability to adapt to such changes. Enhancing this adaptive capacity presents a
      practical way of coping with climate change. Adaptive capacity could be increased
      by enabling the African livestock owner to cope better with animal health
      problems through appropriate policy measures and institutional support.
      Developing an effective and sustainable animal health service, associated
      surveillance and emergency preparedness systems and sustainable disease control
      and prevention programmes is perhaps the most important strategy for dealing with
      climate change in many African countries.

PMID- 18819678
TI  - Managing animal disease risk in Australia: the impact of climate change.
AB  - Climate change is one of a number of factors that are likely to affect the future
      of Australian agriculture, animal production and animal health, particularly when
      associated with other factors such as environmental degradation, intensive animal
      production, an increasing human population, and expanding urbanisation.
      Notwithstanding the harshness and variability of Australia's climate, significant
      livestock industries have been developed, with the majority of products from such
      industries exported throughout the world. A critical factor in achieving market
      access has been an enviable animal health status, which is underpinned by first
      class animal health services with a strong legislative basis, well-trained staff,
      engagement of industry, effective surveillance, good scientific and laboratory
      support, effective emergency management procedures, a sound quarantine system,
      and strong political support. However, enhancements still need to be made to
      Australia's animal health system, for example: re-defining the science-policy
      interface; refining foresight, risk analysis, surveillance, diagnostics, and
      emergency management; improving approaches to education, training, technology
      transfer, communications and awareness; and engaging more with the international
      community in areas such as capacity building, the development of veterinary
      services, and disease response systems. A 'one health' approach will be adopted
      to bring together skills in the fields of animal, public, wildlife and
      environmental health. These initiatives, if managed correctly, will minimise the
      risks resulting from global warming and other factors predisposing to disease.

PMID- 18819679
TI  - Climate change impacts and risks for animal health in Asia.
AB  - The threat of climate change and global warming is now recognised worldwide and
      some alarming manifestations of change have occurred. The Asian continent,
      because of its size and diversity, may be affected significantly by the
      consequences of climate change, and its new status as a 'hub' of livestock
      production gives it an important role in mitigating possible impacts of climate
      variability on animal health. Animal health may be affected by climate change in
      four ways: heat-related diseases and stress, extreme weather events, adaptation
      of animal production systems to new environments, and emergence or re-emergence
      of infectious diseases, especially vector-borne diseases critically dependent on
      environmental and climatic conditions. To face these new menaces, the need for
      strong and efficient Veterinary Services is irrefutable, combined with good
      coordination of public health services, as many emerging human diseases are
      zoonoses. Asian developing countries have acute weaknesses in their Veterinary
      Services, which jeopardises the global surveillance network essential for early
      detection of hazards. Indeed, international cooperation within and outside Asia
      is vital to mitigating the risks of climate change to animal health in Asia.

PMID- 18819680
TI  - Climate change and animal diseases in South America.
AB  - Climate strongly affects agriculture and livestock production and influences
      animal diseases, vectors and pathogens, and their habitat. Global warming trends
      predicted in the 2007 Intergovernmental Panel on Climatic Change (IPCC) report
      for South America are likely to change the temporal and geographical distribution
      of infectious diseases, including those that are vector-borne such as bluetongue,
      West Nile fever, vesicular stomatitis and New World screwworm. Changes in
      distribution will be partially modulated by El Nino Southern Oscillation events,
      which will become more frequent and lead to a greater frequency of droughts and
      floods. Active disease surveillance for animal diseases in South America,
      particularly for vector-borne diseases, is very poor. Disease reporting is often
      lacking, which affects knowledge of disease distribution and impact, and
      preparedness for early response. Improved reporting for animal diseases that may
      be affected by climate change is needed for better prevention and intervention
      measures in susceptible livestock, wildlife and vectors in South America. This
      requires contributions from multidisciplinary experts, including meteorologists,
      epidemiologists, biologists and ecologists, and from local communities.

PMID- 18819681
TI  - [Patterns and modalities of illicit drug consumption in France].
AB  - After recalling the current patterns and trends of illicit drug use in France,
      the MILDT president outlined a four-year plan of prevention, treatment,
      enforcement and research. The overriding aim is to reduce overall drug
      consumption and thereby to diminish its morbidity and mortality, and its negative
      impact on the family and society. The president ended by describing the public
      tools and resources available to reach these objectives, and underlined the
      central role of MILDT in developing and coordinating these tools.

PMID- 18819682
TI  - [Role of the French Research Institute for Overseas Development (Institut de
      Recherche pour le Developpement, IRD)].
AB  - IRD is a French public scientific and technological institution, jointly overseen
      by the Ministries of Research and Overseas Cooperation. It has three main
      vocations: research, evaluation and training It meets these objectives by
      conducting scientific programs, centered around the relationship between humans
      and their environment in poor countries, in order to contribute to sustainable
      development. IRD has a budget of 218,9 millions euros. It employs 2 235 staff
      including 830 researchers, 1 021 engineers and technicians, and local personnel.
      Forty-two percent of IRD staff are employed overseas, many technicians originate
      from poor countries, and IRD research programs involve researchers from many
      countries. IRD is engaged in several European and international scientific
      programs, and plays a coordinating role for research institutions and
      universities working towards third-world development.

PMID- 18819683
TI  - [The Pasteur Institute is mobilized against emerging diseases].
AB  - The Pasteur Institute, founded nearly 120 year ago, is again mobilizing to
      control emerging and re-emerging infectious diseases (chikungunhya, avia flu,
      etc.) and also to fight major "classical" infections like AIDS and malaria.

PMID- 18819684
TI  - [VEGF, anti-vEGF and diseases].
AB  - Angiogenesis is a rapidly growing research field. Most of the important vascular
      growth factors have been identified in the space of a few years, as well as
      factors responsible for the diferentiation of arteries, veins and lymphatic
      vessels. The role of angiogenesis in tumor growth, exsudative retinopathies and
      some inflammatory diseases has been established in animal models and in the
      clinical setting Angiogenesis is necessary for oxygen and nutrient delivery to
      tissues. Hypoxia is a major determinant of angiogenesis. During adult life the
      vascular network is remarkably stable and there is no active angiogenesis. The
      endothelium is quiescent, except in some physiological circumstances such as the
      female reproductive cycle and muscular exercise The same molecular and cellular
      mechanisms as those that occur during embryonic angiogenesis are involved in
      physiological and pathological neoangiogenesis. Vascular endothelial growth
      factor (VEGF) plays a major role, and VEGF inhibition is a promising therapeutic
      approach to some tumoral and ocular diseases.

PMID- 18819685
TI  - [The lesions of Alzheimer's disease: which therapeutic perspectives?].
AB  - The brain lesions associated with Alzheimer's disease are caused by extracellular
      accumulation of Abeta peptide and intracellular accumulation of tau protein.
      Abeta peptide makes the core of the senile plaque (the "focal deposit"); it is
      also present in the extracellular "diffuse deposits" and in the vessel walls.
      Neurofibrillary tangles, and neuropil threads are composed of hyperphosphorylated
      tau that also accumulates in the processes of the corona of the senile plaque.
      The Abeta deposits first involve the neocortex, while the tau pathology is
      initially found in the hippocampal region. Abeta deposits first occur in the
      neocortex, while intracellular tau accumulation mainly affect the hippocampal
      region. Abeta peptide deposits are initially found in all the neocortical areas,
      then involve the hippocampus and the subcortical nuclei. Tau lesions successively
      involve the hippocampal regions, multi- and uni-modal areas and finally the
      primary cortices in stereotyped stages. Mutations of APP, the precursor of Abeta
      peptide, cause autosomal dominant familial Alzheimer disease, suggesting that a
      cascade of reactions link Abeta overproduction, tau pathology and the clinical
      phenotype. Transgenic mice bearing the mutated human APP gene (APP mice) develop
      A deposits. Systemic injection of Abeta peptide prevents the deposition of Abeta
      peptide. However, a clinical trial had to be interrupted when meningoencephalitis
      occurred in a significant proportion of treated patients. Post mortem studies
      showed a relative scarcity of Abeta deposits. Forthcoming immunotherapy studies
      should soon show whether the prevention of Abeta deposition interrupts disease
      progression.

PMID- 18819686
TI  - [Alzheimer's disease: cellular and molecular aspects].
AB  - Alzheimer's disease is characterized by the presence of neurofibrillary tangles
      and senile plaque in the brain. Both disorders must be present in order to
      confirm a clinical diagnosis of Alzheimer's disease. Neurofibrillary tangles
      contain hyperphosphorylated microtubule-associated protein tau, while senile
      plaque contains a core of amyloidpeptide derived from its precursor.
      Phosphorylation of both amyloid precursor protein and tau represents a
      biochemical link between the two characteristic lesions of Alzheimer's disease.

PMID- 18819687
TI  - [Alzheimer's disease: therapeutic perspectives].
AB  - Current treatments for Alzheimer's disease aim to compensate for biochemical
      deficits in the brain. They are purely symptomatic and restore the central
      cholinergic deficit. Acetylcholinesterase inhibitors have modest but significant
      efficacy on cognitive disorders, activities of daily living, and the global
      clinical impression. Glutaminergic receptor antagonists are used for more
      advanced forms. Future treatments may be curative, acting specifically on the
      amyloid cascade. Secretase inhibitors and immunotherapy are in the pipeline.
      Trials will begin within a few months and will open up new perspectives.

PMID- 18819688
TI  - [Diagnosis of Alzheimer's disease: the contribution of preclinical research].
AB  - Diagnosis of Alzheimer's disease is still only probabilistic. It is based on
      exclusion criteria and requires several sources of information (e.g
      neuropsychological assessment and morphological neuroimaging). The lack of a
      definite diagnosis in living patients penalizes therapeutic research and impedes
      treatment during the early, mildly symptomatic phase of the disease. Over the
      past ten years, studies of transgenic mice have opened new avenues in
      pathophysiological and preclinical research, and have identified new potential
      biomarkers. The aim of this short review of the recent literature is to examine
      the advantages and pitfalls of using animal models to discover and validate new
      Alzheimer biomarkers.

PMID- 18819689
TI  - [Alzheimer's disease: from brain lesions to new drugs].
AB  - We review the main therapeutic targets in Alzheimer's disease. Current treatments
      include cholinesterase inhibitors and the glutamate-modulating drug memantin.
      Other neurotransmitters such as serotonin, histamine and noradrenaline may also
      be targeted. Although useful, however, these symptomatic treatments do not
      prevent neuronal degeneration and death. Epidemiological studies suggest that
      treatments given for other reasons, such as antiinflammatory agents (including
      NSAIDs), cholesterol-lowering drugs, hormone replacement therapy and
      antioxidants, may prevent or improve Alzheimer-type dementia, but this is not
      always borne out in controlled clinical trials. Prevention of hypertension
      significantly reduces the incidence of vascular dementia and of Alzheimer-type
      dementia, albeit through an unknown mechanism. Alzheimer's disease is
      characterized by two main lesions: amyloid plaques and neurofibrillary tangles
      composed of aggregated A Beta peptides and hyperphosphorylated tau. Active and
      passive immunization against A beta has given promising results. Other exciting
      approaches include modulation of A beta processing by inhibiting BACE1 or gamma
      secretase or upregulating alpha-secretase; A beta peptide catabolism; inhibition
      of beta fibrillization; and reducing tau phosphorylation or inhibiting tau
      aggregation. More remote possibilities include gene therapy and the use of growth
      factors to increase neurogenesis.

PMID- 18819690
TI  - [Forensic psychiatry].
AB  - CURRENT SITUATION: in France about 700 psychiatrists are licensed to determine
      criminal responsibility before the courts, in other words to assess whether a
      criminal was capable of knowing what he or she was doing or of controlling him or
      herself Criminals who are considered irresponsible are committed to psychiatric
      hospitals. Criminals who are considered to have diminished judgment or control
      may nonetheless be prosecuted and jailed Psychiatric experts may also be asked to
      predict aggressive behaviour, and to identify determinants of crime. Too often
      the answers are not fully grounded in science, and this is not made sufficiently
      clear. There are 26 psychiatric wards in French prisons, which only treat inmates
      who accept to be treated. When prisoners are prescribed compulsory treatment,
      they are discharged from prison and transferred to a psychiatric ward. This
      situation is more and more frequent but is not the most convenient: it delays
      treatment and does not facilitate long-term therapeutic relationships.
      Responsibility or pragmatism? About 20% of French prison inmates are psychotic,
      and these individuals are at risk of repetitive violent behaviour if left
      untreated. The main question is not one of criminal responsibility, but rather
      the most effective response to antisocial behaviour: is punishment or medical
      treatment the most effective way of preventing future crimes and protecting
      society? Ethical aspects: the situation could be improved by a number of
      measures. For example, training in forensic psychiatry should be obligatory
      before accreditation before a Court, and psychiatric diagnoses should be based
      systematically on the ICD10. Psychiatrists have a special duty to inform on
      advances and uncertainties in their field, in terms of diagnosis, prognosis and
      treatment.

PMID- 18819691
TI  - [How to discuss death with a dying child: can a story help?].
AB  - Is it necessary--and possible--to discuss death with a terminally ill child? How
      should one approach the subject? A recent Swedish study demonstrates the benefits
      for parents who discuss with their child his or her imminent death, and examines
      the ways in which caregivers can help such parents. The mother of one child
      treated in our unit recently wrote a story 48 hours before her child's death. The
      story served to broach a number of questions often raised by dying children and
      their families: fear of the unknown, of being replaced, the inevitability of
      death, grief and fear of being forgotten... Since 2004, the story has been given
      to several families with dying children in our unit. In order to evaluate the
      story's impact on families and to determine whether a document which stimulates
      dialogue should continue to be given to parents, we asked the first thirteen to
      fill out a questionnaire. The results confirmed that the story was experienced as
      something positive and that it helped parents to talk with their children. The
      results of our study lead us to conclude that the medical profession should lend
      its full support to families who wish to engage in this dialogue with their
      children. This study also raises many questions and should be part of a global
      accompaniment strategy. With our support, an illustrated story book called
      Falikou was published in October 2006.

PMID- 18819692
TI  - [Analysis of the variables affecting patients' memorization and interpretation of
      information on thyroidectomy-related risks].
AB  - We prospectively analyzed patients' memorisation and interpretation of
      preoperative information on the risks of thyroidectomy. This study was conducted
      in an academic tertiary care referral center, based on an inception cohort of 280
      patients who were consecutively informed of the risks of thyroidectomy
      (unilateral laryngeal immobility, bilateral laryngeal immobility, hypocalcemia,
      common surgical complications, and perioperative death) by the same surgeon
      during the period 2003-2006. Univariate analysis was used to identify factors
      affecting memorisation and interpretation of the information delivered. After
      being informed of the risks, 14.6% of patients declined surgery, and 5% decided
      to postpone the operation for a few months. Among the 215 patients who underwent
      thyroidectomy, 0.9% remembered all five risks, 17.2% three or four, 61.4% one or
      two, and 20.4% none. The number of risks remembered did not vary over time. Age,
      occupation, and the year of the analysis influenced memorisation. In the
      immediate post-operative period, 85.5% of the patients had a positive opinion and
      45.1% a negative opinion of the preoperative information, and 35.3%
      simultaneously expressed positive and negative opinions. The number of
      preoperative visits and the interval between the final preoperative visit and
      surgery both affected the patients' interpretation of the information. Patient
      memorisation of information on surgical risks is poor, and this results in major
      stress for the patient. After receiving this information, a significant
      proportion of patients decide to forego surgery.

PMID- 18819693
TI  - [Use of the capture-recapture method to assess the frequency of "serious" adverse
      drug reactions: experience of Toulouse University Hospital].
AB  - There is evidence that the methods classically used to identify and quantify
      adverse drug reactions (ADRs), based on spontaneous reporting or computerized
      medical databases, are not exhaustive. Spontaneous notifications to regional
      pharmacovigilance centers suffer from under-reporting Combining different sources
      could improve our knowledge of ADR frequency. The aim of this study was to
      estimate the incidence of serious ADRs handled in medical wards of a French
      university hospital, using data from the Programme de Medicalisation des Systemes
      d'Information (PMSI) and spontaneous reports recorded in the French Pharmaco
      Vigilance Database. The study period was the first 6 months of 2001. From the
      PMSI, we selected all hospitalization summaries that included an ICD-10 code
      related to a potential ADR. From the French Pharmaco Vigilance Database, we
      selected all serious ADRs that occurred during the study period and were reported
      by physicians working in the University Hospital. After identifying cases
      recorded in both sources, we applied the capture-recapture method in order to
      estimate the real number of ADRs. From the PMSI, we identified 274 different
      hospital stays involving an ADR. Out of 241 reports selected from the French
      Pharmaco Vigilance Database, we retained 151 ADRs for analysis. Fifty-two ADRs
      were found in both databases, giving an estimated total of 796 serious ADRs [95%
      confidence interval (CI) 638, 954], corresponding to 2.9% of inpatients (95% CI
      2.3, 3.5) during the first half of 2001. This study confirms the lack of
      exhaustiveness of ADR reporting, whatever the data source, and underlines the
      value of merging data from different databases.

PMID- 18819694
TI  - [Multiple sclerosis: a degenerative disease?].
AB  - Multiple sclerosis (MS) is an organ-specific autoimmune disease targeting central
      nervous system myelin. The clinical course results from an interplay between
      relapses and progression. Relapses are the clinical counterpart of acute focal
      inflammation of the central nervous system, whereas progression is due to chronic
      diffuse neurodegeneration. According to the autoimmune theory, successive
      clinical and especially subclinical relapses eventually lead to irreversible
      disability, while the accumulation of focal lesions explains the diffuse
      neurodegeneration. Things are not that simple, however. Relapses are not the main
      contributor to irreversible disability, as shown both in individual patients and
      at the population level. Likewise, MRI studies show that focal lesions are not
      entirely responsible for the diffuse neurodegeneration. Relapse prevention with
      disease-modifying drugs does not markedly influence the onset of irreversible
      disability or the progression of cerebral atrophy. In fact, acute inflammatory
      focal lesions and relapses may be the "tree that hides the forest". Indeed,
      clinical progression and chronic diffuse neurodegeneration both play a key role,
      developing independently of relapses and focal lesions. Should MS therefore be
      considered a primary degenerative disorder rather than a primary autoimmune
      disease? Not yet: recent pathological studies clearly demonstrate the presence of
      disseminated activated microglial-like inflammatory cells in the central nervous
      system. These could lead to a deleterious inflammatory process, even if not
      specifically autoimmune, unlike the inflammation occurring in acute lesions. If
      this pathogenetic picture of the disease is correct, then it has implications for
      therapeutic strategies. Indeed, treating the acute focal inflammation, as we
      successfully do nowadays, will not be enough. It will also be necessary to
      extinguish the slow-burning diffuse inflammation nested in the central nervous
      system behind the blood-brain barrier. This is the new therapeutic challenge in
      MS.

PMID- 18819695
TI  - [Regenerative capacity in multiple sclerosis].
AB  - Disability in multiple sclerosis is related to demyelination and axonal injury.
      Remyelination has been shown to occur in the different forms of the disease. In
      addition to restoring nerve conduction, myelin repair has a major role in
      preventing neurodegeneration. However, although sometimes extensive,
      remyelination is usually insufficient. Our understanding of the cellular and
      molecular mechanisms underlying the success or failure of myelin repair has
      benefited from lesion analysis in multiple sclerosis, and from in vivo and in
      vitro models of myelination and remyelination. This also provides potential
      targets for therapeutic intervention aimed at promoting endogenous remyelination.

PMID- 18819696
TI  - [Multiple sclerosis in children: environmental risk factors].
AB  - An 8-year cohort study of nearly 500 children with a first demyelinating event,
      with only 8% of losses to follow-up, has changed our view of pediatric MS. The
      risk of MS was not increased by HBV vaccination, but was increased by passive
      smoking at home.

PMID- 18819697
TI  - [New vaccination strategies].
AB  - Pasteur put vaccination on an empiric and experimental basis during the 1880s,
      and vaccine development proceeded slowly until the second World War. During this
      period live vaccines against bacterial and viral diseases were developed by
      attenuation through passage in animals and killed microbes were inactivated
      without destroying their immunogenicity. Moreover, knowledge of bacterial toxins
      and polysaccharides permitted the development of new vaccines for several
      epidemic diseases. At the beginning of the third century of vaccination,
      classical methods are still providing new vaccines, but molecular biology and
      genetic engineering have begun to influence vaccine development. In addition, for
      the first time basic immunology is contributing to the domain of vaccinology.
      Thus, the current trends in vaccine development are as follows: reassortment of
      segmented genomes, attenuated strains recombined with genes from pathogens,
      vectors carrying foreign genes, replication-defective particles, DNA plasmids,
      and reverse vaccinology, among others. Also, new methods of vaccine delivery
      besides injection will be used and new adjuvants will be added to vaccines in
      order to stimulate specific responses. The future of vaccination is promising.

PMID- 18819698
TI  - [The horse as an athlete: an animal model of choice for sports medicine:
      sonographic studies of joint disorders].
AB  - Equine diagnostic sonography was initially used for the diagnosis and
      documentation of tendon injuries. Since 1990, this technique, along with
      radiography, has become an indispensable imaging procedure for the diagnosis of
      equine joint injuries. Sonography provides precise diagnostic information on the
      synovial membrane and fluid, the articular cartilage, subchondral bone and joint
      margins, the ligaments and menisci, and the anatomical structures involved in
      periarticular swelling or enlargement. Improvements in ultrasound machines and
      better superficial and deep image resolution allow us to examine every joint of
      the frontlimbs and hindlimbs, including the most proximal, as well as most of the
      joints of the equine vertebral column, pelvis and head. As a professional
      athlete, the horse is an excellent animal model of sport-related joint disorders
      in humans. The large size of its anatomical structures facilitates high-quality
      imaging. Sensitive and specific diagnostic sonography of joint injuries requires
      strict standardization of the technical approach to each joint structure and also
      a precise knowledge of equine joint anatomy.

PMID- 18819699
TI  - [Prevention of zoonoses: creation of a unit for early detection of animal
      infections].
AB  - In a context in which known and potential zoonoses are emerging (simian
      retrovirus infections, SRAS, West Nile, H5N1 avian influenza, etc.), French army
      veterinarians have been tasked with assessing epidemiological risks related to
      animals in proximity with troops, particularly during foreign operations. They
      have already completed surveys of more than 70 infections (toxoplasmosis,
      leishmaniasis, rickettiosis, leptospirosis, Q fever, hepatitis E, Rift valley
      fever, etc.). The strategy consists of detecting pathogenic agents ("the right
      sample, at the right time, and kept in the right conditions") in reservoir
      animals and vectors, upstream of epidemics. The authors propose to set up a
      flexible and mobile animal infection detection unit, working closely with
      hospital physicians, veterinarians and specialized microbiology laboratories.
      This would be an efficient tool for anticipating, preventing and combating
      zoonoses.

PMID- 18819700
TI  - [Inductively coupled plasma: a promising new tool with application in human
      toxicology and public health].
AB  - The authors describe the use of inductively coupled plasma to detect 32 metals
      and metalloids in blood, urine, hair and nails. They also report the first case
      of gadolinium overdose documented by blood analysis with this method Metal
      speciation, a new approach developed in our laboratory, can distinguish between
      toxic and non toxic metals.

PMID- 18819701
TI  - [Myocardial infarction and oral contraceptives].
AB  - Shortly after the introduction of oral contraceptives in 1960, myocardial
      infarction (MI) started to emerge as a major adverse effect. Its mechanism and
      pathophysiology have remained elusive. Many epidemiological studies identified
      smoking, hypertension, diabetes and hypercholesterolemia as risk factors for
      coronary thrombosis in young women using oral contraceptives. The pathogenesis of
      MI involves two phases: atherosclerotic plaque formation, and thrombotic arterial
      occlusion. The use of very low doses of estrogen (less than 50 microg of ethinyl
      estradiol) and new progestagens have minimized the vascular risks. However, the
      risk remains in women who smoke or have other atherosclerotic risks factors. We
      report 12 cases of MI in women aged 35 +/- 5 years who were using different types
      of oral contraceptive. All the women had several risks factors, such as smoking,
      hypertension, hypercholesterolemia, obesity, and type II diabetes. Coronarography
      during the acute phase showed either occlusions on severe atherosclerotic
      stenoses or thrombosis of arteries with non significant atherosclerotic plaque.
      In two cases coronarography was normal after thrombolysis. Ten women recovered
      without sequelae, but reversible left ventricular dysfunction occurred in the
      other two women, who did not have acute-phase revascularization. Recent case
      control studies show that the cardiovascular risk is very low with new, third
      generation combined contraceptives. But the risk of MI increases with age,
      smoking, hypertension, dyslipidemia and diabetes. The absolute risks associated
      with oral contraceptives and smoking are higher in women over 35, because of the
      steeply rising incidence of atherosclerosis. It is mandatory to respect the
      classical contraindications of oral contraception.

PMID- 18819702
TI  - Slumping during sculpturing of composite materials.
AB  - OBJECTIVES: This study investigated the slumping characteristics of four
      composite materials during sculpturing prior to their polymerization. METHODS:
      Four different composite materials were used to measure shape deformation due to
      slumping. Silicon impressions of the occlusal plane of three different molars
      were used as a mould for the composite samples. The surface of the samples was
      digitized with a laser scanner (400 slices, lateral resolution: 25 microm). Scans
      were made after 1-4 min. The 3D data sets were numerically superimposed with
      matching software and differences were calculated relative to the baseline
      measurement. RESULTS: The amount of surface deformation increases with increasing
      observation time. The average coefficient of variation was 0.2. The largest mean
      amount of slumping was observed for ELS with tooth mould 1 (150.0 microm), and
      for Clearfil Majesty with tooth mould 2 (98.3 microm) and mould 3 (42.8 microm).
      Miris 2 Dentin and Synergy D6 Enamel were rather similar and seem to exhibit
      little deformation. The slump flow of ELS and Clearfil Majesty was up to 400%
      higher than the formers. The deformation could be sorted in the following order
      "mould 3"<"mould 2"<"mould 1" for all materials and all observation time. There
      was a significant influence (p<0.05) of the three factors, time, mould and
      composite type (ANOVA). SIGNIFICANCE: This specific method provides a
      reproducible approach for the assessment of the handling characteristics of
      composite materials. The results can identify slumping differences and assist in
      collecting information about the feasibility of a material for certain
      indications.

PMID- 18819703
TI  - A material model for internal stress of dental composites caused by the curing
      process.
AB  - OBJECTIVE: To compare the build-up of internal stresses in four different dental
      composites (Venus, Tetric Ceram, Ceram X mono and Filtek Supreme) during the
      curing reaction, based on the results of a former paper on polymerization
      kinetics, and to characterize the developing mechanical behavior for different
      modes of activation using experimental methods and simulation tools. METHODS: A
      four-parameter viscoelastic model combined with a curing model and a kinetic
      model was developed to simulate the mechanical behavior in three dimensions using
      the finite element software ABAQUS. In order to study the influence of slow
      polymerization behavior on the mechanical properties, the length of the
      activation period was doubled at half intensity of the curing light. RESULTS:
      Using a model which describes the complex interplay of stiffness, flowability,
      curing speed and activation intensity during the curing process gives deeper
      insight into the spatial and temporal build-up of stresses. An advantageous
      reaction kinetic or a lower stiffness can compensate for the effect of a higher
      polymerization shrinkage on the resulting peak stress. The evolution of stress is
      not directly proportional to the level of shrinkage of the composites.
      SIGNIFICANCE: A material model which includes the developing mechanical
      characteristics of a curing dental composite can be used to develop and optimize
      dental materials and to assess the effect of different treatment strategies (i.e.
      mode of photo-polymerization, filling geometries, interfacial strength).

PMID- 18819704
TI  - Treatment of type 2 diabetes with incretin-based therapies.

PMID- 18819706
TI  - Innovative finance for women and children.

PMID- 18819705
TI  - Liraglutide versus glimepiride monotherapy for type 2 diabetes (LEAD-3 Mono): a
      randomised, 52-week, phase III, double-blind, parallel-treatment trial.
AB  - BACKGROUND: New treatments for type 2 diabetes mellitus are needed to retain
      insulin-glucose coupling and lower the risk of weight gain and hypoglycaemia. We
      aimed to investigate the safety and efficacy of liraglutide as monotherapy for
      this disorder. METHODS: In a double-blind, double-dummy, active-control, parallel
      group study, 746 patients with early type 2 diabetes were randomly assigned to
      once daily liraglutide (1.2 mg [n=251] or 1.8 mg [n=247]) or glimepiride 8 mg
      (n=248) for 52 weeks. The primary outcome was change in proportion of
      glycosylated haemoglobin (HbA(1c)). Analysis was done by intention-to-treat. This
      trial is registered with ClinicalTrials.gov, number NTC00294723. FINDINGS: At 52
      weeks, HbA(1c) decreased by 0.51% (SD 1.20%) with glimepiride, compared with
      0.84% (1.23%) with liraglutide 1.2 mg (difference -0.33%; 95% CI -0.53 to -0.13,
      p=0.0014) and 1.14% (1.24%) with liraglutide 1.8 mg (-0.62; -0.83 to -0.42,
      p<0.0001). Five patients in the liraglutide 1.2 mg, and one in 1.8 mg groups
      discontinued treatment because of vomiting, whereas none in the glimepiride group
      did so. INTERPRETATION: Liraglutide is safe and effective as initial
      pharmacological therapy for type 2 diabetes mellitus and leads to greater
      reductions in HbA(1c), weight, hypoglycaemia, and blood pressure than does
      glimepiride.

PMID- 18819707
TI  - Micro-stamped surfaces for the patterned growth of neural stem cells.
AB  - We present a method for patterning neural stem cells based on pre-patterning
      polypeptides on a cell-repellent surface (poly(ethylene) oxide-like, PEO-like,
      plasma-deposited films). The method ensures cell attachment and stability for
      several weeks, as well as it allows cell migration and differentiation. Various
      patterns of approximately 1 nm thick cell adhesive poly-L-lysine (PLL) have been
      created on a cell-repellent PEO-like matrix by microcontact printing using
      different array configurations and printing conditions. The cell-repellent
      property of PEO-like film determined the confinement of the cells on the printed
      patterns. Optimization of the printing method showed that the most homogeneous
      patterns over large areas were obtained using PLL diluted in carbonate buffer
      (100mM) at pH 8.4. Neural stem cells cultured on the PLL patterns in low serum
      and in differentiating medium over 20 days exhibited a good confinement to the
      polypeptide domains. The number of cells attached increased linearly with the
      micro-stamped PLL area. The cells were able to extend random axon-like
      projections to the outside of the patterns and presented high amount of
      ramifications when cultured in differentiating medium. Migration and axon-like
      outgrowth have been successfully guided by means of an interconnected squares
      configuration. The surfaces are suitable for controlling the patterning of stem
      cells and provide a platform for the assessment of the way how different cell
      arrangements and culture conditions influence cell interactions and cell
      developmental processes.

PMID- 18819708
TI  - Ultra low fouling zwitterionic polymers with a biomimetic adhesive group.
AB  - Biomimetic polymers with a zwitterionic moiety for ultra low fouling and a
      catechol end group for surface anchoring have been developed. Binding tests of
      the adhesive polymers on various surfaces, including amino (NH(2)), hydroxyl
      (OH), and methyl (CH(3)) terminated self-assembled monolayers (SAMs) along with
      bare gold, were performed under acidic and basic conditions. Protein adsorption
      from single protein solutions of fibrinogen, lysozyme, and complex media of 10
      100% blood plasma and serum was measured using a surface plasmon resonance (SPR)
      sensor. Under optimized conditions, the coated surfaces are highly resistant to
      non-specific protein adsorption from both single protein solutions and blood
      serum/plasma. Furthermore, the 3-day accumulation of Pseudomonas aeruginosa on
      the coated surfaces was evaluated in situ in a laminar flow chamber. Results show
      that the coated surfaces are highly resistant to bacterial adhesion and biofilm
      formation. This work demonstrates a convenient and efficient method for using
      zwitterionic polymers with a catechol anchor group to achieve ultra low fouling
      surfaces via surface modification, for applications in complex media.

PMID- 18819709
TI  - The hydrolysis of cationic polycarboxybetaine esters to zwitterionic
      polycarboxybetaines with controlled properties.
AB  - In this work, we report a new class of materials, cationic polycarboxybetaine
      esters, which have unique properties when they interact with proteins, DNAs, and
      bacteria. These cationic polymers can be converted to nontoxic and nonfouling
      zwitterionic polymers upon their hydrolysis. Due to their unique properties, they
      are very promising for a wide range of applications, such as highly effective
      gene delivery carriers and environmentally friendly antimicrobial coatings. Three
      positively charged polyacrylamides, of which the pedant groups bear
      carboxybetaine ester groups, were synthesized. These three polymers have
      different spacer groups between the quaternary ammonium and the ester groups.
      Their hydrolysis behaviors were studied using proton NMR under different NaOH
      concentrations. Their interactions with biomolecules and microorganisms before
      and after hydrolysis were demonstrated by protein adsorption/resistance, DNA
      condensation/release, and antimicrobial properties. The polymers were grafted
      onto a gold-coated surface covered with initiators using surface-initiated atom
      transfer radical polymerization (ATRP). Fibrinogen adsorption was measured by
      surface plasmon resonance (SPR) sensors. While the polymer-grafted surfaces have
      high protein adsorption, the surfaces became nonfouling after hydrolysis. Linear
      polymers were also synthesized and DNA/polymer complexes were evaluated. Agarose
      gel electrophoresis shows that DNA can be condensed into nanoparticles by the
      cationic polymers before hydrolysis and released from the DNA/polymer complexes
      upon the hydrolysis of the cationic polymers into zwitterionic polymers. The
      complexes formed were characterized by dynamic light scattering measurements. In
      addition, the interactions of linear polymers with bacteria were also evaluated.
      The polycarboxybetaine ester with a pentene spacer exhibits evident antimicrobial
      properties when they are incubated with Gram negative bacteria (Escherichia
      Coli). The polymer can be converted to a nontoxic polycarboxybetaine after
      hydrolysis. This work shows that the biological properties of polycarboxybetaine
      esters can be dramatically changed via controlled hydrolysis.

PMID- 18819710
TI  - Single-dose mitoxantrone in combination with continuous infusion intermediate
      dose cytarabine plus etoposide for treatment of refractory or early relapsed
      acute myeloid leukemia.
AB  - This prospective phase II clinical trial evaluated the effects of single-dose
      mitoxantrone (36 mg/m2 on day 1) in combination with continuous infusion
      intermediate-dose cytarabine plus etoposide in 25 patients with refractory or
      early relapsed acute myeloid leukemia (AML). We compared the results of our
      current study with those of a previous phase II trial, which had the same
      eligibility criteria and chemotherapy schedule except that a conventional divided
      dose of mitoxantrone (12 mg/m2 on days 1-3) was used. The complete remission (CR)
      rate was significantly lower with the single-dose mitoxantrone regimen than with
      the divided-dose regimen (24.0% vs. 51.5%; P=0.034), mainly owing to an increased
      incidence of hypoplastic deaths. CR duration and overall survival were not
      significantly different between the two regimens. In conclusion, single-dose
      mitoxantrone was inferior to conventional divided-dose mitoxantrone for treatment
      of refractory or early relapsed AML in terms of CR rate.

PMID- 18819711
TI  - Expression profile of Eph receptors and ephrin ligands in healthy human B
      lymphocytes and chronic lymphocytic leukemia B-cells.
AB  - Increasing information relates some Eph receptors and their ligands, ephrins
      (EFN), with the immune system. Herein, we found that normal B-cells from
      peripheral blood (PB) and lymph nodes (LN) showed a differential expression of
      certain Eph/EFN members, some of them being modulated upon in vitro stimulation
      including EFNA1, EFNA4, EphB6 and EphA10. In contrast, PB CLL B-cells showed a
      more heterogeneous Eph/EFN profile than their normal PB B-cell counterparts,
      expressing Eph/EFN members frequently found within the LN and activated B-cells,
      specially EFNA4, EphB6 and EphA10. Two of them, EphB6 and EFNA4 were further
      related with the clinical course of CLL patients. EphB6 expression correlated
      with a high content of ZAP-70 mRNA and a poor prognosis. High serum levels of a
      soluble EFNA4 isoform positively correlated with increasing peripheral blood
      lymphocyte counts and lymphadenopathy. These findings suggest that Eph/EFN might
      be relevant in normal B-cell biology and could represent new potential prognostic
      markers and therapeutic targets for CLL.

PMID- 18819712
TI  - Immune system and thiols: some peculiarities of thiol exchange.
AB  - We show that for the system of SH-containing compounds of the organism (cysteine,
      in particular) there are conditions leading to immunosuppression, which occurs
      when the level of amino acid cysteine in blood serum increases. The arising
      "overload" of free sulfhydryl groups inactivates antibodies of the IgM class of
      any specificity restoring disulphide intramolecular bonds and then the number of
      immune antibody-producing cells, mitotic activity of T- and B-lymphocytes and
      interleukin-2 synthesis are lowered and the mobility of surface immunoglobulin B
      lymphocytes receptors is damaged. Determination of total blood sulfhydryl groups
      for diagnostics of developing immunodeficiency disorder is not informative
      because of the high individual fluctuation of blood sulfhydryl groups number. It
      is the determination of inhibitory properties of blood serum regarding to IgM
      antibodies of any class and specificity in test system in vitro that is
      informative. It is proved clinically and by experiments that in the course of
      infectious inflammatory process the long-lasting inhibitory properties of blood
      serum are unfavorable and lead to the lingering course of disease. On the
      contrary, in case of autoimmune pathology the appearance of inhibitory properties
      of blood serum is a favorable prognostic factor.

PMID- 18819713
TI  - Effects of natural and chemical stressors on Enchytraeus albidus: can oxidative
      stress parameters be used as fast screening tools for the assessment of different
      stress impacts in soils?
AB  - Enchytraeids are important organisms of the soil biocenosis. They improve the
      soil pore structure and the degradation of organic matter. These organisms are
      used in standardized testing, using survival and reproduction (6 weeks) as
      endpoints. The use of biomarkers, linked to ecologically relevant alterations at
      higher levels of biological organization, is a promising tool for Environmental
      Risk Assessment. Here, enchytraeids were exposed for different time periods (two
      days and three weeks) to different soils (OECD artificial soil, different
      compositions in its organic matter, clay or pH value, and LUFA 2.2 natural soil)
      and different chemicals (Phenmedipham and copper). The main question addressed in
      the present study was if the effects of chemicals and different soil properties
      are preceded by alterations at the sub-cellular level, and if these endpoints may
      be used reliantly as faster screening tools for the assessment of different
      stress conditions in soils. The parameters measured in E. albidus whole body
      were: lipid peroxidation (LPO), total glutathione (TG), as well as the enzymatic
      activities of superoxide dismutase (SOD), catalase (CAT), glutathione reductase
      (GR), glutathione peroxidase (GPx) and glutathione S-transferase (GST). The
      results showed that biomarker responses in E. albidus were significantly affected
      by the soil type (GST, CAT, GPx, GR and LPO) and the duration of exposure in OECD
      artificial soil (GST, GPx, GR, CAT and LPO) but not in LUFA 2.2 natural soil. For
      the abiotic factors studied, after 2 days, low pH decreased significantly the TG
      levels and the activities of CAT and GR,and low OM also significantly decreased
      CAT and GR activities. After 3 weeks, differences in soil properties caused a
      decrease in GR and GPx activities, whereas increased GST activity was observed
      due to low organic matter and pH. Copper significantly increased the activities
      of CAT, GPx and GR, and decreased the activity of GST after 2 days as well as
      inscreasing LPO levels after 3 weeks. Phenmedipham increased LPO levels,
      associated with increased levels of TG as well as increased activities of CAT and
      GPx and decreased GST activity after 3 weeks exposure. This study shows that both
      abiotic and chemical stresses could be followed through biomarker analysis and
      that some of these determinations are potential endpoints in a quick soil
      contamination assessment procedure.

PMID- 18819714
TI  - Assessment of soil quality using bioaccessibility-based models and a biomarker
      index.
AB  - Bioavailability in heterogeneous media such as soils is a multi-factorial concept
      which ranges from soil chemistry to toxicity. The complexity of this factor has
      been tackled by various studies pinpointing its relevancy for laboratory to field
      extrapolation of toxicity data. As contaminant bioavailability on these sites is
      virtually unknown, a global assessment of this issue has been conducted on soils
      impacted by antitank firing from a Canadian Range and Training Area (RTA) and
      contaminated by energetic materials (EM) and metals. Yet, the descriptive results
      acquired from this survey require further in-depth analysis so as to enhance
      understanding of soil health status. Statistical models as well as an index
      integrating biomarker responses were derived from this database and are proposed
      as diagnostic, explanatory and possibly predictive tools for soil bioavailability
      and quality assessment. Relationships associating bioaccessible contaminant
      levels to soil properties allowed to clarify contaminant behaviour in energetic
      material (EM)-contaminated soils. Likewise, models expressing biomarker responses
      as a function of bioaccessible contaminant concentrations contributed to identify
      the contaminants causing toxicity in earthworms and to the comprehension of those
      toxic effects. The index of biomarker response was adapted from similar concepts
      applied in the aquatic environment and is an original contribution to terrestrial
      sites. The biomarker index data were in agreement with soil contamination
      profiles and represent therefore an interesting tool for soil quality appraisal.
      Such tools also offer a promising potential for the management of contaminated
      soils.

PMID- 18819715
TI  - Early intervention in bipolar disorders: clinical, biochemical and neuroimaging
      imperatives.
AB  - In the absence of clear targets for primary prevention of many psychiatric
      illnesses, secondary prevention becomes the most feasible therapeutic target, and
      is best encompassed by the concept of early intervention. This construct
      encompasses the goals of minimising diagnostic delay and the prompt initiation of
      clinically appropriate therapy. This paper develops the rationale for early
      intervention in bipolar disorder. Three interrelated themes are discussed; the
      clinical data supporting the value of prompt diagnosis and treatment in bipolar
      disorder, the putative biochemical mechanisms underlying the pathophysiological
      processes, and the parallel concept of neuroprotection, and the developing
      neuroimaging data that supports early intervention. Early initiation of
      appropriate therapy may potentially facilitate improved clinical outcomes, and
      further might allow the secondary prevention of the sequelae of untreated
      illness, which include the deleterious impact on family relationships,
      psychosexual and vocational development, identity and self-concept and self
      stigma.

PMID- 18819716
TI  - Flexible bronchoscopy and interdisciplinary collaboration in pediatric large
      airway disease.
AB  - OBJECTIVE: Demonstrate the benefits of a multidisciplinary pediatric airway team
      prepared to evaluate and treat otolaryngology patients with flexible
      bronchoscopy. DESIGN: Case series. SETTING: Tertiary, academic children's
      hospital. PATIENTS: 10 children (5 male, 5 female age range 2 months-16 years)
      presenting with complex symptoms potentially referable to large airways.
      INTERVENTION: Flexible bronchoscopy for diagnostic (bronchoalveolar lavage,
      ciliary biopsy, assess ongoing surgical intervention, and rule in or rule out
      foreign body; N=6) or therapeutic (evacuate bronchial mucus plug, laser
      subglottis when patient has fused cervical spine, and distal instillation [fibrin
      glue for bronchopleural fistula and dornase alpha for plastic bronchitis]; N=4).
      MAIN OUTCOME MEASURE: Retrospectively ask if flexible bronchoscopy and
      interdisciplinary management improved patient care in these select otolaryngology
      cases. RESULTS: 10/10 patients benefited from interdisciplinary management
      including flexible bronchoscopy. CONCLUSION: Our experience illustrates many uses
      for flexible bronchoscopy in otolaryngology patients, and suggests that an airway
      team prepared to use flexible bronchoscopy will create opportunities for improved
      patient care.

PMID- 18819717
TI  - Low power radiofrequency ablation for symptomatic microcystic lymphatic
      malformation of the tongue.
AB  - Although many head and neck surgeons agree that complete surgical excision is the
      treatment of choice for lymphatic malformation, the infiltrating nature of
      microcystic lymphatic malformations and the involvement of vital structures of
      the head and neck make total removal nearly impossible in most cases. Recently
      radiofrequency ablation was introduced for the treatment of microcystic lymphatic
      malformations of the oral cavity; it destroys lesion tissues at low temperature
      (40-70 degrees C) with minimal damage to adjacent structures. However, high
      energy (800-1200 J) and general anesthesia for radiofrequency ablation can hinder
      the easy and repetitive application of radiofrequency to patients. To overcome
      this limitation of radiofrequency ablation for microcystic lymphatic
      malformations, we used the same technique with a lower power (6 W, less than 100
      J per site) radiofrequency ablation in an office-based setting under local
      anesthesia in a child with a microcystic lymphatic malformation of the whole
      tongue, that was associated with recurrent bleeding and swelling. The repetitive
      low power energy radiofrequency ablation of the microcystic lymphatic
      malformation of the tongue was safe and effective; it provided the patient with
      symptomatic relief without recurrence at follow-up. Therefore, our modification
      of radiofrequency ablation of the microcystic lymphatic malformations could be
      technically feasible and easily applicable; our result suggests that it can be a
      useful alternative treatment option to relieve symptoms from microcystic
      lymphatic malformation of the oral cavity.

PMID- 18819718
TI  - Pediatric hearing impairment caregiver experience: impact of duration of hearing
      loss on parental stress.
AB  - OBJECTIVES: Caregivers of children who are deaf/hard of hearing have been
      reported to have greater stress than caregivers of children with normal hearing.
      The time of diagnosis is a particularly stressful time and stress levels may
      change over time based on varying needs at different life events. Thus, we
      hypothesized that stress experienced by caregivers evolves over time and is
      impacted by the duration since the diagnosis of hearing loss. METHODS: The 68
      item pediatric hearing impairment caregiver experience (PHICE) is a validated
      questionnaire used to measure stress. The PHICE was administered to 152
      caregivers of children with permanent hearing loss. Domain scores were converted
      into z-scores for analysis of trends of stress over time. RESULTS: Parents of
      children whose hearing loss was identified more than 60 months ago reported
      higher stress levels regarding educational aspects of their child's needs as
      compared to parents of children with less than 24 months or 24-60 months duration
      since diagnosis. Parents of children diagnosed with hearing loss within the
      preceding 24 months reported higher stress levels in the area of healthcare than
      parents of children diagnosed greater than 24 months ago. CONCLUSIONS: Parental
      stressors change over time with respect to the time of diagnosis of hearing
      impairment. This phenomenon was observed irrespective of the age of diagnosis of
      hearing loss. As professionals serving families of children with hearing loss, we
      should be aware of changing stressors over time and identify the appropriate
      support services for families to meet those changing needs. By addressing those
      evolving stressors, the families' ability to support and improve the outcomes for
      their children who are deaf or hard of hearing may be enhanced.

PMID- 18819719
TI  - Biomarkers by gender.
AB  - Regressions were determined for age-related human biological functions containing
      information for both genders. Their intercept T(0) on the age axis (x) was used
      as a measure of the aging rate. The peak of the frequency distribution of T(0)
      was consistent with earlier estimates. The frequency distribution of the ratio R
      of T(0)(women)/T(0)(men) peaked at unity. However, when the T(0)-values were
      divided into two groups, namely those relating to functions involving musculature
      vs. the rest, respectively, the ratio of R for musculature was <1 and that for
      the latter significantly >1. This suggests that men are the stronger gender when
      musculature is involved, but, more broadly, women are "biologically stronger".

PMID- 18819720
TI  - Isolation, identification and toxigenic potential of ochratoxin A-producing
      Aspergillus species from coffee beans grown in two regions of Thailand.
AB  - In 2006 and 2007, 32 Thai dried coffee bean samples (Coffea arabica) from two
      growing sites of Chiang Mai Province, and 32 Thai dried coffee bean samples
      (Coffea canephora var. robusta) from two growing sites of Chumphon Province,
      Thailand, were collected and assessed for the distribution of fungi with the
      potential to produce ochratoxin A (OTA). The overall percentage of fungal
      contamination in coffee was 98% and reduced to 60% after surface disinfection.
      There were remarkable ecological differences in the composition of ochratoxigenic
      species present in these two regions. Arabica coffee bean samples from the North
      had an average of 78% incidence of colonization with Aspergillus of section
      Circumdati with Aspergillus westerdijkiae and A. melleus as the predominant
      species. Aspergillus spp. of section Nigri were found in 75% of the samples
      whereas A. ochraceus was not detected. Robusta coffee beans from the South were
      98-100% contaminated with predominantly A. carbonarius and A. niger. A.
      westerdijkiae was only found in one sample. The diversity of the fungal
      population was probably correlated with the geographical origin of the coffee,
      coffee cultivar, and processing method. Representative isolates of section
      Circumdati (52) and Nigri (82) were examined for their OTA production using HPLC
      with fluorescence detection. Aspergillus westerdijkiae (42 isolates out of 42),
      A. steynii (13/13), and A. carbonarius (35/35) in general produced large amounts
      of OTA, while one isolate of A. sclerotiorum produced intermediate amounts of
      OTA. 13% of the A. niger isolates produced OTA in intermediate amounts. OTA
      levels in coffee bean samples were analyzed using the Ridascreen OTA ELISA kits.
      Of the 64 coffee bean samples analyzed, 98% were contaminated with OTA in levels
      of <0.6-5.5 microg/kg (Arabica) and 1-27 microg/kg (Robusta). Presence of OTA in
      representative coffee samples was also confirmed by LC-MS/MS after ion-exchange
      purification.

PMID- 18819721
TI  - Comparative study of the pln locus of the quorum-sensing regulated bacteriocin
      producing L. plantarum J51 strain.
AB  - Lactobacillus plantarum J51 strain was isolated from a Rioja red wine and it
      showed bacteriocin activity against a wide range of lactic acid bacteria of
      oenological importance. These characteristics conferred L. plantarum J51 a high
      interest both in wine microbiology and in the study of bacteriocin production. In
      this work the bacteriocin production regulated under the "quorum-sensing"
      mechanism is observed and the pln locus of the bacteriocin-producing L. plantarum
      J51 is fully characterized. A 20,667 bp fragment was completely sequenced
      (GenBank accession number DQ340868), and showed five operons (plNC8betaalphac,
      plnLR-like, plnABCD, plnEFI, plnGHSTUVW) and a new region containing a putative
      operon with three new orfs that could encode a putative two-peptide bacteriocin.

PMID- 18819722
TI  - The quest for orthologs: finding the corresponding gene across genomes.
AB  - Orthology is a key evolutionary concept in many areas of genomic research. It
      provides a framework for subjects as diverse as the evolution of genomes, gene
      functions, cellular networks and functional genome annotation. Although
      orthologous proteins usually perform equivalent functions in different species,
      establishing true orthologous relationships requires a phylogenetic approach,
      which combines both trees and graphs (networks) using reliable species phylogeny
      and available genomic data from more than two species, and an insight into the
      processes of molecular evolution. Here, we evaluate the available bioinformatics
      tools and provide a set of guidelines to aid researchers in choosing the most
      appropriate tool for any situation.

PMID- 18819723
TI  - Re-positioning genes to the nuclear envelope in mammalian cells: impact on
      transcription.
AB  - The spatial organization of the genome within the nucleus is thought to
      contribute to genome functions. A key component of the nuclear architecture is
      the nuclear envelope, which is often associated with inactive chromatin. Studies
      in budding yeast indicate that nuclear position can directly affect gene
      function. However, the causal relationship between gene position and gene
      activity in mammalian cells has been more elusive. Several groups recently
      addressed this issue by tethering genes to the inner nuclear membrane. Their
      studies show that the nuclear periphery is not refractory to gene transcription,
      but can modulate the activity of certain genes. The 3D organization of the genome
      might, thus, provide an additional level of regulation necessary for fine-tuning
      gene expression.

PMID- 18819724
TI  - EGFR gene copy number in adenocarcinoma of the lung by FISH analysis:
      investigation of significantly related factors on CT, FDG-PET, and
      histopathology.
AB  - It has been suggested that a high EGFR gene copy number may be an indicator of
      good response to EGFR tyrosine kinase inhibitor therapy and a marker of poor
      prognosis in NSCLC. However, imaging features related to EGFR gene copy number
      status in adenocarcinoma are still unknown. We therefore retrospectively analyzed
      CT, FDG-PET, and histopathologic slides of surgical resected lung adenocarcinoma
      in 132 patients. Tumor characteristics on preoperative chest-CT, such as, GGO
      proportions, tumor diameters, and cavitation; FDG-PET SUV(max); and
      histopathologically determined differentiation degrees and tumor subtypes were
      evaluated. EGFR gene copy number status was categorized as FISH-positive or 
      negative. FISH-positivity was found in 53 patients (40.2%) and was significantly
      more frequent in tumors with a SUV(max)>7.0 (P=0.007). Furthermore, FISH
      negativity was found to be more frequent in tumors with a GGO>50% (P=0.023) and
      diameter <15.5mm (P=0.006) on CT, or a well-differentiated histopathology
      (P=0.002). Moreover, the frequency of FISH-positivity increased as SUV(max)
      increased (P=0.0008) and as the proportion of GGO decreased (P=0.01).
      SUV(max)>7.0 was an independent predictor of FISH-positive results (odds ratio,
      3.941; 95% CI, 1.691-9.182; P=0.01). In conclusion, a high SUV(max) on FDG-PET
      was significantly related to FISH-positive results. A high proportion of GGO,
      small tumor diameter on CT, and a well-differentiated histopathology were more
      frequent in FISH-negative adenocarcinomas.

PMID- 18819725
TI  - Clinicopathological analysis of primary lung carcinoma with heterotopic
      ossification.
AB  - Pulmonary heterotopic ossification is an unusual event. The relationship between
      ossification and lung carcinoma is unclear. The present study analyzed
      clinicopathological features of primary lung carcinoma with heterotopic
      ossification. We reviewed 2269 surgically resected primary lung carcinomas and
      identified 33 with heterotopic ossification, including 15 cases with intratumoral
      heterotopic ossification (IHO) and 18 cases with extratumoral heterotopic
      ossification (EHO). All cases with IHO were adenocarcinomas and 10 of 15 (66.6%)
      cases had confirmed positive mucin staining in the tumor cells. Cases with EHO
      could be divided into three patterns, and each pattern is potentially associated
      with the background conditions of lung parenchyma. Immunohistochemistry, BMP-2
      production was present in 13 of 15 (86.7%) cases with IHO, although, only 4 of 17
      (23.5%) cases with EHO. A prognostic analysis revealed no statistically
      significant difference to be observed between adenocarcinomas with IHO and
      without IHO. The present study suggested that IHO associated with adenocarcinomas
      and BMP-2 production in the tumor cells, whereas EHO was not associated with the
      biology of the carcinoma.

PMID- 18819726
TI  - Milia: a review and classification.
AB  - Milia are frequently encountered as a primary or secondary patient concern in
      pediatric and adult clinics, and in general or surgical dermatology practice.
      Nevertheless, there are few studies on the origin of milia and, to our knowledge,
      there is no previous comprehensive review of the subject. We review the various
      forms of milia, highlighting rare variants including genodermatosis-associated
      milia, and present an updated classification.

PMID- 18819727
TI  - Juvenile pityriasis rubra pilaris: report of 28 cases in Taiwan.
AB  - BACKGROUND: Pityriasis rubra pilaris (PRP) is a papulosquamous dermatosis
      uncommon in juveniles. Large-scale studies are limited, especially from Asian
      countries. OBJECTIVE: We sought to analyze the clinical manifestations of
      juvenile PRP in Taiwanese patients and compare them with reported series in the
      literature. METHODS: The diagnosis of juvenile PRP was made based on clinical
      histopathologic correlation. The therapeutic response and disease course were
      followed up by re-examination of the patients or by telephone. RESULTS: A total
      of 47 patients were identified, with histopathologic confirmation of the clinical
      diagnosis of juvenile PRP in 28 cases. A preponderance of Griffiths' type IV PRP
      (85.7%) rather than type III PRP (14.3%) was found. Palmoplantar hyperkeratosis
      appeared to be a cardinal feature. In patients with type IV PRP, skin lesions in
      areas other than the elbows/knees and palms/soles were common. Treatment with
      systemic acitretin in 6 patients failed to effect a dose- or time-dependent
      improvement. In contrast with other studies, two thirds of our patients with type
      III and IV juvenile PRP had a protracted course lasting more than 3 years.
      LIMITATIONS: This study was a retrospective review. Patient compliance with
      treatment was frequently poor. CONCLUSIONS: Type IV juvenile PRP predominated but
      our cases showed a wider distribution of skin lesions than is typically
      described. When children present with an acute onset of diffuse palmoplantar
      hyperkeratosis, a diagnosis of juvenile PRP should be considered. Because of the
      divergent clinical manifestations of juvenile PRP in different populations, there
      is a need to modify and re-evaluate classification systems based on regional
      differences.

PMID- 18819728
TI  - Aggressive digital papillary adenocarcinoma: a report of two diseases and review
      of the literature.
AB  - Aggressive digital papillary adenocarcinoma (ADPAca) is a rare, underreported,
      and often misdiagnosed malignant tumor of the sweat glands most commonly
      occurring in males in their fifties to seventies. We report two cases of ADPAca
      with important clinical implications. A 54-year-old man presented 3 years after
      digit amputation for ADPAca with new blue nodules on his arm, lymphadenopathy,
      and a lung nodule; he was diagnosed with and treated for metastatic ADPAca. He
      underwent chemotherapy, but died 4 months later. A 15-year-old boy presented with
      an enlarging tumor on his finger occurring after a trauma 3 years earlier. The
      tumor was suspected to be a deep fungal infection or pyogenic granuloma; however,
      results of excisional biopsy revealed an ADPAca. The patient underwent amputation
      and sentinel lymph node examination. No signs of metastases were found, and he is
      alive and well. These cases highlight both the importance of high clinical
      suspicion of digital tumors, even in children, enabling prompt diagnosis and
      treatment and also emphasize the metastatic potential of the tumor and the need
      for aggressive treatment and close long-term follow-up.

PMID- 18819729
TI  - beta-amyloid-related peptides potentiate K+-evoked glutamate release from adult
      rat hippocampal slices.
AB  - Accumulated evidence indicates that amyloid beta (Abeta) peptides, by interacting
      with the central glutamatergic system, can lead to degeneration of neurons
      associated with Alzheimer's disease (AD) pathology. However, very little is
      currently known about the role of Abeta peptides in the regulation of
      glutamatergic function in the normal brain. Given the evidence that Abeta
      peptides are produced constitutively in the normal brain, we investigated the
      possible association of amyloid precursor protein (APP)-containing neurons with
      the vesicular glutamatergic transporter-1 (VGluT1) and measured the effects of
      various Abeta peptides on endogenous glutamate release from adult rat brain
      slices. Our results showed that VGluT1 immunoreactivity is localized in close
      apposition to APP neurons, and that exogenous Abeta(1-40), in a dose-dependent
      (10(-12) to 10(-7)M) manner potently increased K(+)-evoked glutamate release from
      hippocampal slices. This effect was observed with other Abeta peptides such as
      Abeta(1-42), Abeta(1-28) and Abeta(25-35), but not with the reverse Abeta(1-40)
      or Abeta(25-35) sequences. Tetrodotoxin failed to alter the effects of Abeta(1
      40) on glutamate release, which suggests the lack of involvement of voltage
      dependent Na(+) channels. In addition to the hippocampus, Abeta(1-40) was found
      to potentiate K(+)-evoked glutamate release from cortical slices, whereas in the
      striatum the effect did not reach significant levels. These results demonstrate
      that physiological concentrations of Abeta peptides can regulate the release of
      glutamate by acting on glutamatergic terminals. Additionally, the evidence that
      selected regions of the brain are sensitive to Abeta peptides suggests a
      potential link between the deposition of Abeta and the preferential vulnerability
      of brain regions observed in AD pathology.

PMID- 18819730
TI  - Antidyslipidemic and antioxidative activities of 8-hydroxyquinoline derived novel
      keto-enamine Schiffs bases.
AB  - 8-Hydroxyquinoline when subjected to Duff reaction resulted in the formation of
      unexpected 7-methylaminomethylene-8-oxo-7, 8-dihydroquinoline-5-carbaldehyde 2,
      which existed in the keto-enamine form, in which the aromaticity of the relevant
      ring was disrupted, which upon subsequent treatment with various primary amines
      resulted in its nucleophilic substitution of aliphatic methyl amine. These
      interesting novel derivatives were evaluated in vitro for their antioxidant and
      in vivo for their antidyslipidemic and post-heparin lipolytic activities.
      Compound 6 was found to be most active antidyslipidemic and antioxidative agent
      in this series, respectively, and thus represent a new class of promising lead.

PMID- 18819731
TI  - [Excessive sweating related to hydromorphone].
AB  - Diffuse and abundant sweating in a middle age patient evolving for several weeks
      should raise suspicion of malignant lymphoma and infectious or neuroendocrine
      disorders before considering a drug origin. We report a patient who presented
      with severe and invalidating excessive sweating related to hydromorphone therapy
      for vertebral pain. Amongst their many reported side-effects, excessive sweating
      disappearing with discontinuation of the drug have been reported with some
      opiates.

PMID- 18819732
TI  - [Internal medicine physicians' perception of frequency and impact of
      corticosteroid-induced adverse events].
AB  - INTRODUCTION: Whereas internal medicine physicians frequently prescribe systemic
      corticosteroids, it is unknown if they assess adequately the frequency and the
      discomfort caused by corticosteroid-induced adverse events. METHODS: Using an e
      mail questionnaire sent to the 813 internal medicine physicians, members of the
      French National Society of Internal Medicine, we assessed their perception of the
      frequency and the discomfort induced by the adverse events of long-term (that is,
      over or at three months) corticosteroid therapy. At the same time, 121
      corticosteroid-treated patients, consulting in a department of internal medicine
      completed an anonymous questionnaire about the frequency and the discomfort
      caused by the adverse events of their therapy. RESULTS: Three hundred and thirty
      six out of 813 internal medicine physicians answered to the questionnaire
      (response rate: 41%) and 115 of the 121 questionnaires distributed to patients
      were exploitable. The physicians were predominantly male (71%) working mainly in
      tertiary centers (53%). The mean length of corticosteroids therapy for patients
      was 44+/-38 months and the mean daily dosage was 15+/-14mg. Lipodystrophy,
      trophic skin disorders, neuropsychiatric disorders and insomnia were frequent and
      reported by more than half of patients. The frequency of neuropsychiatric and
      skin disorders and of lipodystrophy estimated by practitioners was markedly lower
      than the frequency reported by patients. If morphological changes (weight-gain
      and lipodystrophy) were cited by practitioners as the most discomforting adverse
      event, in agreement with patients' opinion, physicians underestimated the
      discomfort caused by neuropsychiatric disorders and insomnia. CONCLUSION:
      Frequency and discomfort caused by corticosteroid-induced neuropsychiatric
      disorders are underestimated by internal medicine physicians.

PMID- 18819733
TI  - Optimal protein intake in the elderly.
AB  - The recommended dietary allowance (RDA) for protein, as promulgated by the Food
      and Nutrition Board of the United States National Academy of Science, is 0.8 g
      protein/kg body weight/day for adults, regardless of age. This value represents
      the minimum amount of protein required to avoid progressive loss of lean body
      mass in most individuals. There is an evidence that the RDA for elderly may be
      greater than 0.8 g/kg/day. Evidence indicates that protein intake greater than
      the RDA can improve muscle mass, strength and function in elderly. In addition,
      other factors, including immune status, wound healing, blood pressure and bone
      health may be improved by increasing protein intake above the RDA. Furthermore,
      the RDA does not address the recommended intake of protein in the context of a
      balanced diet. Concerns about potential detrimental effects of increased protein
      intake on bone health, renal function, neurological function and cardiovascular
      function are generally unfounded. In fact, many of these factors are improved in
      elderly ingesting elevated quantities of protein. It appears that an intake of
      1.5 g protein/kg/day, or about 15-20% of total caloric intake, is a reasonable
      target for elderly individuals wishing to optimize protein intake in terms of
      health and function.

PMID- 18819734
TI  - Sources of anthropogenic radionuclides in the environment: a review.
AB  - Studies of radionuclides in the environment have entered a new era with the
      renaissance of nuclear energy and associated fuel reprocessing, geological
      disposal of high-level nuclear wastes, and concerns about national security with
      respect to nuclear non-proliferation. This work presents an overview on sources
      of anthropogenic radionuclides in the environment, as well as a brief discussion
      of salient geochemical behavior of important radionuclides. We first discuss the
      following major anthropogenic sources and current developments that have lead, or
      could potentially contribute, to the radionuclide contamination of the
      environment: (1) nuclear weapons program; (2) nuclear weapons testing; (3)
      nuclear power plants; (4) uranium mining and milling; (5) commercial fuel
      reprocessing; (6) geological repository of high-level nuclear wastes that include
      radionuclides might be released in the future, and (7) nuclear accidents. Then,
      we briefly summarize the inventory of radionuclides (99)Tc and (129)I, as well as
      geochemical behavior for radionuclides (99)Tc, (129)I, and (237)Np, because of
      their complex geochemical behavior, long half-lives, and presumably high mobility
      in the environment; biogeochemical cycling and environment risk assessment must
      take into account speciation of these redox-sensitive radionuclides.

PMID- 18819735
TI  - Biogenic volatile organic compounds as a potential stimulator for organic
      contaminant degradation by soil microorganisms.
AB  - The effects of monoterpenes on the degradation of (14)C-2,4-dichlorophenol (DCP)
      were investigated in soils collected from areas surrounding monoterpene and non
      monoterpene-emitting vegetation. Indigenous microorganisms degraded (14)C-2,4-DCP
      to (14)CO(2), after 1d contact time. Degradation was enhanced by prior exposure
      of the soils to 2,4-DCP for 32 d, increasing extents of mineralisation up to 60%.
      Monoterpene amendments further enhanced 2,4-DCP degradation, but only following
      pre-exposure to both 2,4-DCP and monoterpene, with total 2,4-DCP mineralisation
      extents of up to 71%. Degradation was greatest at the higher monoterpene
      concentrations (> or = 1 microg kg(-1)). Total mineralisation extents were
      similar between concentrations, but higher than the control and the 0.1 microg
      kg(-1) amendment, indicating that increases in monoterpene concentration has a
      diminishing enhancing effect. We suggest that monoterpenes can stimulate the
      biodegradation of 2,4-DCP by indigenous soil microorganisms and that monoterpene
      amendment in soils is an effective strategy for removing organic contaminants.

PMID- 18819736
TI  - Remediation of metal polluted mine soil with compost: co-composting versus
      incorporation.
AB  - Trace element contamination of post-industrial sites represents a major
      environmental problem and sustainable management options for remediating them are
      required. This study compared two strategies for immobilizing trace elements (Cu,
      Pb, Zn, and As) in mine spoil: (1) co-composting contaminated soil with organic
      wastes and (2) conventional incorporation of mature compost into contaminated
      soil. Sequential chemical extraction of the soil was performed to determine
      temporal changes in trace element fractionation and bioavailability during
      composting and plant growth. We show that mine spoil can be co-composted
      successfully and this action causes significant shifts in metal availability.
      However, co-composting did not lead to significant differences in metal
      partitioning in soil or in plant metal uptake compared with simply mixing mine
      spoil with mature compost. Both treatments promoted plant growth and reduced
      metal accumulation in plants. We conclude that co-composting provides little
      additional benefit for remediating trace-element-polluted soil compared with
      incorporation of compost.

PMID- 18819737
TI  - Tidal influence on the distribution of hydrophobic organic contaminants in the
      Seine Estuary and biomarker responses on the copepod Eurytemora affinis.
AB  - To elucidate tidally related variations of hydrophobic organic contaminant (HOC)
      bioavailability and the impact of these contaminants on estuarine ecosystems,
      both PCB and PAH concentrations were investigated in the dissolved phase and in
      the suspended particulate material (SPM) of the Seine Estuary. Both PAH and PCB
      highest levels were observed in surface and bottom water when SPM remobilizations
      were maximum, in relation to higher speed currents. In parallel,
      acetylcholinesterase (AChE) and glutathione-S-transferase (GST) activities were
      investigated in the copepod Eurytemora affinis. Significant decreasing AChE
      levels were measured during the tidal cycle and between surface and bottom
      copepods related to salinity and to HOC concentration variations. Significant
      increasing GST levels were also observed when HOC concentrations in the water
      column were the highest. This study underlined the need to standardize sampling
      procedures for biomonitoring studies in order to avoid interfering factors that
      could modify biomarker responses to chemical exposure.

PMID- 18819738
TI  - Polycyclic aromatic hydrocarbon (PAH) contamination of surface sediments and
      oysters from the inter-tidal areas of Dar es Salaam, Tanzania.
AB  - Surface sediment and oyster samples from the inter-tidal areas of Dar es Salaam
      were analyzed for 23 polycyclic aromatic hydrocarbons (PAHs) including the 16
      compounds prioritized by US-EPA using GC/MS. The total concentration of PAHs in
      the sediment ranged from 78 to 25,000 ng/g dry weight, while oyster
      concentrations ranged from 170 to 650 ng/g dry weight. Hazards due to sediment
      contamination were assessed using Equilibrium Partitioning Sediment Benchmarks
      and Threshold Effect Levels. Diagnostic indices and principle component analysis
      were used to identify possible sources. Interestingly, no correlation between
      sediment and oyster concentrations at the same sites was found. This is supported
      by completely different contamination patterns, suggesting different sources for
      both matrices. Hazard assessment revealed possible effects at six out of eight
      sites on the benthic communities and oyster populations. The contribution of PAH
      intake via oyster consumption to carcinogenic risks in humans seems to be low.

PMID- 18819739
TI  - Aberrant pattern of scanning in prosopagnosia reflects impaired face processing.
AB  - Visual scanpath recording was used to investigate the information processing
      strategies used by a prosopagnosic patient, SC, when viewing faces. Compared to
      controls, SC showed an aberrant pattern of scanning, directing attention away
      from the internal configuration of facial features (eyes, nose) towards
      peripheral regions (hair, forehead) of the face. The results suggest that SC's
      face recognition deficit can be linked to an inability to assemble an accurate
      and unified face percept due to an abnormal allocation of attention away from the
      internal face region. Extraction of stimulus attributes necessary for face
      identity recognition is compromised by an aberrant face scanning pattern.

PMID- 18819740
TI  - Re-intervention in glass ionomer restorations: what comes next?
AB  - AIM: The aim of this study is to report the subsequent treatment provided, over
      the 11 years' data available, when a re-intervention was considered clinically
      necessary on a glass ionomer (GI) restoration. METHODS: A detailed sample of
      treatment records of patients has been established at the Dental Practice
      Division of the NHS Business Services Authority, consisting of records containing
      directly placed restorations for adult patients from January 1991. This database
      contains the records of over half a million restorations. For each direct
      restoration placed, the subsequent history of that tooth was consulted, for the
      period up to December 2001, and the restorations divided into three groups:
      amalgam, composite and GI, the latter being subdivided into anterior teeth,
      premolars, and molars. RESULTS: Data on 164,036 directly placed restorations were
      analyzed. Results indicated that, for amalgam and composite restorations, the
      subsequent treatment was likely to be another restoration in the same material.
      For GI (24,947 restorations), only one third of restorations, overall, were
      followed by another GI. In anterior teeth, GI restorations were more often
      followed by composite than by GI, this trend increasing with increasing time
      interval since restoration. For premolar teeth, the GI restoration was most
      likely to be followed by another GI within 4 years, with an increasing trend
      towards re-intervention by an amalgam or composite in older restorations. For
      molar teeth, GI restorations were more likely to be followed by an amalgam
      restoration. CONCLUSION: For GI restorations, on re-intervention, there is
      variation in the next restoration material used according to tooth position and
      time interval to re-intervention. GI restorations in anterior and molar teeth are
      not likely to be followed by another GI restoration.

PMID- 18819741
TI  - Influence of chlorine dioxide on cell death and cell cycle of human gingival
      fibroblasts.
AB  - OBJECTIVES: The effects of chlorine dioxide (ClO2), sodium hypochlorite (NaOCl),
      and hydrogen peroxide (H2O2) on cell death and the cell cycle of human gingival
      fibroblast (HGF) cells were examined. METHODS: The inhibition of HGF cell growth
      was evaluated using a Cell Counting Kit-8. The cell cycle was assessed with
      propidium iodide-stained cells (distribution of cells in G0/G1, S, and G2/M
      phases) using flow cytometry. The patterns of cell death (necrosis and apoptosis)
      were analyzed using flow cytometry with annexin V-FITC/PI staining. RESULTS: The
      lethal doses for 50% of the cells (LD50) of ClO2, NaOCl, and H2O2 were 0.16,
      0.79, and 0.11 mM, respectively. All three dental disinfectants induced G0/G1
      cell cycle arrest. H2O2 induced apoptosis at concentrations of 0.05 and 0.1 mM,
      while NaOCl and ClO2 did not induce significant apoptosis at any concentration
      examined. CONCLUSIONS: These results suggest that ClO2 is sufficient for use as a
      dental disinfectant compared with H2O2 or NaOCl.

PMID- 18819742
TI  - In vitro remineralization effects of grape seed extract on artificial root
      caries.
AB  - Grape seed extract (GSE) contains proanthocyanidins (PA), which has been reported
      to strengthen collagen-based tissues by increasing collagen cross-links. We used
      an in vitro pH-cycling model to evaluate the effect of GSE on the
      remineralization of artificial root caries. Sound human teeth fragments obtained
      from the cervical portion of the root were stored in a demineralization solution
      for 96 h at 37 degrees C to induce artificial root caries lesions. The fragments
      were then divided into three treatment groups including: 6.5% GSE, 1,000 ppm
      fluoride (NaF), and a control (no treatment). The demineralized samples were pH
      cycled through treatment solutions, acidic buffer and neutral buffer for 8 days
      at 6 cycles per day. The samples were subsequently evaluated using a
      microhardness tester, polarized light microscopy (PLM) and confocal laser
      scanning microscopy (CLSM). Data were analyzed using ANOVA and Fisher's tests
      (p<0.05). GSE and fluoride significantly increased the microhardness of the
      lesions (p<0.05) when compared to a control group. PLM data revealed a
      significantly thicker mineral precipitation band on the surface layer of the GSE
      treated lesions when compared to the other groups (p>0.05), which was confirmed
      by CLSM. We concluded that grape seed extract positively affects the
      demineralization and/or remineralization processes of artificial root caries
      lesions, most likely through a different mechanism than that of fluoride. Grape
      seed extract may be a promising natural agent for non-invasive root caries
      therapy.

PMID- 18819743
TI  - Gold nanoparticles conjugated to [Tyr3]octreotide peptide.
AB  - A multifunctional system of gold nanoparticles (AuNP) capped by the
      [Tyr(3)]Octreotide (TOC) peptide was prepared and characterized by transmission
      electron microscopy (TEM) and UV-Vis, infrared and fluorescence spectroscopy.
      AuNP and AuNP-TOC fluorescence emission spectra were obtained both in solution
      and in murine AR42J-tumor tissues. Results suggest that AuNP were functionalized
      with TOC through interactions with the N-terminal amine of the phenylalanine, the
      amide groups and possibly with the indole group of the tryptophan residue. The
      fluorescence analyses in tissue revealed a recognition of the AuNP-TOC conjugate
      for the neuroendocrine tumor because of the lower energy position of the
      fluorescence resonance (692 nm) with respect to that of the AuNP in the same
      tumoral tissue (684 nm). The emission band observed in the near-infrared region
      (692 nm) opens the possibility for AuNP-TOC use in bioimaging.

PMID- 18819744
TI  - Fluorescence studies on the photophysical properties and encapsulation behavior
      of acetaminophen in different environments.
AB  - A systematic study on the spectroscopy and photophysical properties of widely
      used analgesic and anti-pyretic drug acetaminophen (NAPAP) was presented using
      steady state and time-resolved fluorescence spectroscopy. The results in
      homogeneous solvents were compared with those in bio-mimicking environments of
      cyclodextrin and micellar cavities. Extensive theoretical calculations using time
      dependent density functional theory (TDDFT) were also done to substantiate the
      spectral assignment as well as to compare the structure and stability of possible
      hydrogen bonded conformations of NAPAP in aqueous medium. Facile proton
      dissociation occurs due to extensive charge redistribution in the excited state.
      The variation in fluorescence yield and the life time of excited state species in
      cyclodextrin cavities and micellar medium is due to shift in acid-base
      dissociation equilibrium in these environments.

PMID- 18819745
TI  - The treatment paradigm shifts again on prostate cancer.

PMID- 18819746
TI  - Aberrant methylation of candidate tumor suppressor genes in neuroblastoma.
AB  - CpG island hypermethylation has been recognized as an alternative mechanism for
      tumor suppressor gene inactivation. In this study, we performed methylation
      specific PCR (MSP) to investigate the methylation status of 10 selected tumor
      suppressor genes in neuroblastoma. Seven of the investigated genes (CD44,
      RASSF1A, CASP8, PTEN, ZMYND10, CDH1, PRDM2) showed high frequencies (> or =30%)
      of methylation in 33 neuroblastoma cell lines. In 42 primary neuroblastoma
      tumors, the frequencies of methylation were 69%, CD44; 71%, RASSF1A; 56%, CASP8;
      25%, PTEN; 15%, ZMYND10; 8%, CDH1; and 0%, PRDM2. Furthermore, CASP8 and CDH1
      hypermethylation was significantly associated with poor event-free survival. Meta
      analysis of 115 neuroblastoma tumors demonstrated a significant correlation
      between CASP8 methylation and MYCN amplification. In addition, there was a
      correlation between ZMYND10 methylation and MYCN amplification. The MSP data,
      together with optimized mRNA re-expression experiments (in terms of concentration
      and time of treatment and use of proper reference genes) further strengthen the
      notion that epigenetic alterations could play a significant role in NB
      oncogenesis. This study thus warrants the need for a global profiling of gene
      promoter hypermethylation to identify genome-wide aberrantly methylated genes in
      order to further understand neuroblastoma pathogenesis and to identify prognostic
      methylation markers.

PMID- 18819747
TI  - The role of weathering on fly ash charge distribution during triboelectrostatic
      beneficiation.
AB  - Triboelectrostatic beneficiation of coal combustion fly ashes with high-unburned
      carbon contents can produce low-carbon ash products having value as mineral
      admixtures and meeting technical requirements for replacing cement in concrete.
      This capability is a result of establishing bipolar charge on mineral ash versus
      carbon particles where, typically, unburned carbon attains positive surface
      charge and ash attains negative surface charge under the tribocharging conditions
      employed in triboelectrostatic technologies. However, long-term exposure of fly
      ash to weathering conditions, such as moisture or high humidity, before
      beneficiation is known to dramatically diminish carbon-ash separation
      efficiencies. Although experimentation has shown that water soluble surface
      species can be redistributed on fly ash particles after exposure to moisture,
      which could affect the extent of charging and polarities, measurement of the
      actual amount of charge and polarity on particles after weathering exposure
      versus after removal of surface moisture has not been accomplished. Hence, a new
      experimental methodology was developed and applied to measure charge
      distributions on tribocharged ash and carbon particles in a fly ash that had been
      exposed to weathering conditions for 6 months before and after removal of the
      surface moisture. Weathered ash particles were found to have an average zero
      charge, whereas carbon particles attained an average negative charge, opposite of
      the normal polarity for carbon. Although the extent of uncharged particles
      decreased and ash particles attained an average negative charge after drying,
      carbon particles attained only an average zero charge. These changes were
      reflected in very small increases in carbon-ash separation efficiency, in
      contrast to previous beneficiation tests in which fly ash drying led to
      significant increases in carbon-ash separation efficiency. It is suggested that
      removal of surface moisture in the absence of other processes like surface ion
      redistribution would beneficially impact carbon-ash triboelectrostatic
      beneficiation.

PMID- 18819748
TI  - Hybrid processes for the treatment of cattle-slaughterhouse wastewater using
      aluminum and iron electrodes.
AB  - Electrocoagulation (EC) of cattle-slaughterhouse wastewater, which is
      characterized by (i) high turbidity (up to 340 Nephelometric turbidity units),
      (ii) increased chemical oxygen demand (COD) concentration (4200 mg L(-1)), and
      (iii) a dark color, was investigated with the purpose of lowering the turbidity
      and COD concentration to levels below the permitted direct-discharge limits. Iron
      and aluminum were used as electrode materials. Experiments were conducted to
      evaluate the effects of current density, initial pH, and supporting electrolyte
      (Na(2)SO(4)) dosage on the performance of the system. COD removal increased with
      increase in current density. The original pH of wastewater (7.8) was found to be
      preferable for both the electrode materials. Higher concentrations of Na(2)SO(4)
      caused an increase in COD removal efficiency, and energy consumption was
      considerably reduced with increasing conductivity. Hybrid processes were applied
      in this work to achieve higher COD removal efficiencies. In the case of aluminum
      electrode, polyaluminum chloride (PAC) was used as the coagulant aid for the
      aforesaid purpose. COD removal of 94.4% was obtained by adding 0.75 g L(-1) PAC.
      This removal efficiency corresponded to effluent COD concentration of 237 mg L(
      1), which meets the legal requirement for discharge from slaughterhouses in
      Turkey. In the case of iron electrode, EC was conducted concurrent with the
      Fenton process. As a result, 81.1% COD removal was achieved by adding 9%
      H(2)O(2). Consequently, hybrid processes are inferred to be superior to EC alone
      for the removal of both COD and turbidity from cattle-slaughterhouse wastewater.

PMID- 18819749
TI  - Reductive destruction and decontamination of aqueous solutions of chlorinated
      antimicrobial agent using bimetallic systems.
AB  - Palladium, ruthenium and silver were investigated as catalysts for the
      dechlorination of dichlorophen (DCP, 2,2'-methylenebis(4-chlorophenol)), an
      antimicrobial and anthelmintic agent largely used as algicide, fungicide and
      bactericide. Experiments were undertaken under oxic and anoxic conditions for
      experimental durations up to 180 min (3h). The anoxic conditions were achieved by
      purging the solutions with nitrogen gas. Reactions were performed in a 12+/-0.5
      mg L(-1) DCP solution (V=20 mL) using 0.8 g of Fe(0) (40 g L(-1)). Along with
      micrometric Fe(0), five Fe(0)-plated systems were investigated: Pd (1%), Ru
      (0.01%), Ru (0.1%), Ru (1%) and Ag (1%). Metal plating was controlled by atomic
      absorption spectroscopy. DCP degradation was monitored using: (i) two HPLC
      devices, (ii) ion chromatography, (iii) UV and fluorescence spectrophotometry.
      Results indicated: (i) total dechlorination with Fe/Pd, (ii) partial
      dechlorination (40%) with Fe/Ru, and no reaction with Fe/Ag. DCP is vanished
      completely after 90 min of contact with Fe/Pd following a first order kinetic.
      The observed degradation rate k(obs) was about (3.98+/-0.10)x10(-2)min(-1), the
      calculated half-life t(1/2) about 17.4+/-0.9 min and a t(50) about 10.1+/-0.5
      min. A DCP degradation pathway map was also proposed.

PMID- 18819750
TI  - Density functional calculations on the thermodynamic properties of a series of
      nitrosocubanes having the formula C8H8-x(NO)x)x=1-8.
AB  - Recent studies have suggested that octanitrocubane and heptanitrocubane may be
      two of the most powerful non-nuclear high-energy materials currently known.
      Progressive substitution of the hydrogen atoms on cubane for nitroso groups is
      expected to also produce a new potential high-energy material, which should have
      thermodynamic properties similar to nitrocubane. In this study we predict
      optimized structures, vibrational frequencies, enthalpies of formation, and
      specific enthalpies of combustion for a series of nitrosocubanes ranging from
      mononitrosocubane to octanitrosocubane. Our results indicate, on the basis of the
      specific enthalpies of combustion alone, that mononitrosocubane should make the
      best new high-energy material; however, we speculate that the velocity of
      detonation of octa- and heptanitrosocubane will make them better high-energy
      materials.

PMID- 18819751
TI  - Comparative evaluation of two ivermectin injectable formulations against
      psoroptic mange in feedlot cattle.
AB  - A study was carried out to compare the efficacy of two injectable formulations of
      ivermectin, Ivomec,(1) Merial (IVM reference) and Ivogell,(2) Intervet (IVM
      generic) in the treatment of psoroptic mange (Psoroptes ovis) in Charollais
      feedlot cattle. A total of 22 animals were ranked in order of the severity of
      mange and allocated to 11 replicates of 2 animals each. Within each replicate,
      one animal was randomly allocated to IVM reference product treatment (Group 1)
      and one to IVM generic (Group 2). Animals were treated on Day 0 and on Day 8 at
      the recommended dosage of 200 microg ivermectin/kg bodyweight. The
      pharmacokinetics profiles (pK) of both IVM formulations were evaluated in plasma
      samples taken from 6 cattle randomly chosen per group on Day 0, before treatment,
      and then at 6, 12, 24 hours and daily from Day 2 to Day 7 after the treatment on
      Day 0. Additionally, the severity of mange lesions was assessed and mites were
      counted in skin scrapings on Days 0, 8, 15 and 25. Animals were weighed on Day 0
      and 25 and body weight and average daily gains (ADG) were evaluated. No
      statistical differences were found between the cattle of the two groups in any pK
      parameters, although the mean IVM plasma concentrations in cattle treated with
      the IVM reference product were consistently higher than those found in cattle
      treated with the generic compound. By Day 25, all animals in Group 1 had
      recovered clinically and parasitologically from psoroptic mange while cattle from
      Group 2 still had mange lesions and, in two animals, living mites were found in
      the skin scrapings; these differences were significant (P<0.001). The mean body
      weight of the two groups was significantly different on Day 25 (P<0.01) when
      animals in Group 1 weighed 20 kg more than those in Group 2. In conclusion,
      despite similarities in their pharmacokinetic profiles and formulations, the
      clinical efficacy of the two injectable formulations of IVM differed
      significantly in their therapeutic efficacy against psoroptic mange in feedlot
      cattle up to 25 days after treatment: this difference in response was reflected
      in an incomplete clinical and parasitological response in Group 2 and a slower
      growth rate.

PMID- 18819752
TI  - Echinococcus multilocularis infections in domestic dogs and cats from Germany and
      other European countries.
AB  - A cross-sectional survey was conducted to estimate the prevalence of Echinococcus
      multilocularis and E. granulosus infections in domestic dogs and cats from
      Germany and other European countries. Faecal samples of 21,588 dogs and 10,650
      cats routinely submitted to a private veterinary laboratory between June 2004 and
      June 2005 were examined using the ZnSO(4)-NaCl flotation method. Taeniid eggs
      were detected in 54 (0.25%) and 37 (0.34%) of the canine and feline faecal
      samples, respectively. Taeniid eggs were separated and subjected to a DNA
      preparation and a modified two-step PCR for the detection of Echinococcus spp.
      based on mitochondrial 12S rRNA genes. PCR products from Echinococcus-negative
      but cestode-positive reactions were cloned and sequenced to determine the Taenia
      species. E. multilocularis DNA was specifically amplified in 43 (0.24%) and 25
      (0.23%) of the samples from dogs and cats, respectively. E. granulosus DNA was
      not detected in any sample, while, E. multilocularis-positive samples were
      detected in dogs from Germany only, those of cats originated from Germany,
      Denmark and The Netherlands. The prevalence of E. multilocularis egg-positive
      canine samples was significantly higher in southern (0.35%) than in northern
      Germany (0.13%). In contrast, no significant regional difference was observed in
      cats from Germany. Taeniid eggs from Echinococcus-negative samples and from a few
      samples with macroscopically detected Taenia sp. proglottids were identified as
      eggs of T. crassiceps (n=8), T. martis, T. serialis, T. polyacantha, T.
      taeniaeformis and T. pisiformis in dogs (n=1 of each) and T. taeniaeformis (n=11)
      in cats. The spectrum of cestodes detected in domestic dogs and cats indicate the
      consumption of small rodents as infection source. The high proportion of E.
      multilocularis-positive samples, suggest domestic dogs and cats as a possible
      source of E. multilocularis infection for humans.

PMID- 18819753
TI  - Increased occurrence of weaknesses in attention testing in patients with
      Hashimoto's thyroiditis compared to patients with other thyroid illnesses.
AB  - Previous studies suggest disturbances of the central nervous system (CNS) in
      patients with Hashimoto's thyroiditis (HT), independently of thyroid function
      disorders. In the present prospective study, neuropsychological testing was
      performed for the first time in 26 euthyroid patients with HT compared to 25
      euthyroid patients undergoing hormonal treatment for goitre or after thyroid
      surgery. We investigated executive function, attention, visual and verbal memory
      as well as acoustic working memory with established neuropsychological tests and
      detected no significant differences between the two groups. In addition, test
      results were expressed as z-score which is defined as the deviation of an
      individual's value from the mean value of a reference population, divided by the
      standard deviation of the reference population. Thereby, we found significantly
      more HT patients with a z-score of less than -1.5 in the d2 test than in the
      control group (total score I, HT vs. control group: 10 vs. 3, p=0.0302; total
      score II, HT vs. control group: 11 vs. 1, p=0.0013). The d2 test, which measures
      processing speed, rule compliance, and quality of performance, allows for a
      neuropsychological estimation of individual attention performance. HT patients
      with results below the normal range in the d2 attention test showed a significant
      increased mean value of anti-thyroid peroxidase antibodies compared to HT
      patients with normal test results (371.4+/-187.2IU/l vs. 69.3+/-28.7IU/l,
      p<0.05). In conclusion, our results point to subtle brain dysfunction in a
      subgroup of patients with HT even in euthyroid state. This could either be due to
      an association with an unknown autoimmune disorder affecting the CNS or a
      pathogenetic role of thyroid antibodies themselves.

PMID- 18819754
TI  - The relationship between heart rate variability and inflammatory markers in
      cardiovascular diseases.
AB  - INTRODUCTION: Recent evidence implicates a cholinergic anti-inflammatory pathway.
      Because vagus nerve activity mediates some heart rate variability (HRV), this
      qualitative review examines the literature concerning circulating cytokines and
      HRV in cardiovascular function in humans. This qualitative review examines the
      literature concerning circulating cytokines and HRV in cardiovascular function in
      humans. METHODS: Thirteen studies on HRV, inflammation, and cardiovascular
      function were located by electronic library search and descriptively reviewed.
      RESULTS: The relationship between HRV and inflammation was studied in healthy
      controls, patients with acute or stable coronary heart disease (CHD), patients
      with metabolic syndrome or impaired glucose tolerance and patients with kidney
      failure. Investigations focused mainly on Interleukin-6 (IL-6) and C-reactive
      peptide (CRP). The majority of reviewed studies reported that parasympathetic
      nervous system tone as inferred from heart rate variability is inversely related
      to inflammatory markers (r values between -0.2 and -0.4). The relationships with
      inflammatory markers were similar whether derived from ECG signals as short as 5
      30min or from 24-h ECG readings for HRV analyses. While inflammatory markers
      appear to be related to HRV, it is a mistake to assume that the traditional
      "vagal measures" of HRV (such as high frequency heart rate variability) are the
      driving factors. Indeed, low frequency heart rate variability, a complex measure
      reflecting both parasympathetic and sympathetic activity, is the more commonly
      associated measure linked to inflammatory markers. DISCUSSION: Heart rate
      variability is inversely correlated with inflammatory markers in healthy
      individuals as well as in those with cardiovascular diseases.

PMID- 18819755
TI  - Fluctuation of latent inhibition along the estrous cycle in the rat: modeling the
      cyclicity of symptoms in schizophrenic women?
AB  - Latent inhibition (LI) is a cross-species selective attention phenomenon
      manifested as poorer conditioning of stimuli that had been experienced as
      irrelevant prior to conditioning. Disruption of LI by pro-psychotic agents such
      as amphetamine and its restoration by antipsychotic drugs (APDs) is a well
      established model of psychotic symptoms of schizophrenia. There is evidence that
      in schizophrenic women symptom severity and treatment response fluctuate along
      the menstrual cycle. Here we tested whether hormonal fluctuation along the
      estrous cycle in female rats (as determined indirectly via the cellular
      composition of the vaginal smears) would modulate the expression of LI and its
      response to APDs. The results showed that LI was seen if rats were in estrus
      during pre-exposure stage and in metestrus during the conditioning stage of the
      LI procedure (estrus-metestrus) but not along the remaining sequential phases of
      the cycle (metestrus-diestrus, diestrus-proestrus and proestrus-estrus).
      Additionally, the efficacy of typical and atypical APDs, haloperidol and
      clozapine, respectively, in restoring LI depended on estrous condition. Only LI
      disruption in proestrus-estrus exhibited sensitivity to both APDs, whereas LI
      disruption in the other two phases was alleviated by clozapine but not
      haloperidol. Our results show for the first time that both the expression of LI
      and its sensitivity to APDs are modulated along the estrous cycle, consistent
      with fluctuations in psychotic symptoms and response to APDs seen along women's
      menstrual cycle. Importantly, the results indicate that although both low and
      high levels of hormones may give rise to psychotic-like behavior as manifested in
      LI loss, the pro-psychotic state associated with low hormonal level is more
      severe due to reduced sensitivity to typical APDs. The latter constellation may
      mimic states of increased vulnerability to psychosis coupled with reduced
      treatment response documented in schizophrenic women during periods associated
      with low levels of hormones.

PMID- 18819757
TI  - Susceptibility to systemic lupus erythematosus may be related to gene dosage
      effect of the X chromosome.

PMID- 18819756
TI  - Associations between body mass index and substance use disorders differ by
      gender: results from the National Epidemiologic Survey on Alcohol and Related
      Conditions.
AB  - Alcohol, illicit drugs, and nicotine can affect appetite and body weight, but few
      epidemiologic studies have examined relationships between body mass index (BMI)
      and substance use disorders. This study used logistic regression to examine
      effects of BMI and gender on risk for DSM-IV substance use disorders in a sample
      of 40 364 adults. Overweight and obesity were associated with increased risk for
      lifetime alcohol abuse and dependence in men but not women. Overweight and
      obesity were associated with decreased risk for past-year alcohol abuse in women.
      BMI was not associated with illicit drug use disorders. Overweight and obese men
      were at decreased risk for both lifetime and past-year nicotine dependence.
      Overweight women were at increased risk for lifetime nicotine dependence, and
      obese women were at decreased risk for past-year nicotine dependence. Further
      research is needed to identify reasons for observed gender differences in
      relationships between BMI and substance use disorders.

PMID- 18819758
TI  - How gout inhibits the development of cell-mediated autoimmune disease.

PMID- 18819759
TI  - Alcohol and opioid dependence medications: prescription trends, overall and by
      physician specialty.
AB  - Over the past decade, advances in addiction neurobiology have led to the approval
      of new medications to treat alcohol and opioid dependence. This study examined
      data from the IMS National Prescription Audit (NPA) Plus database of retail
      pharmacy transactions to evaluate trends in U.S. retail sales and prescriptions
      of FDA-approved medications to treat substance use disorders. Data reveal that
      prescriptions for alcoholism medications grew from 393,000 in 2003 ($30 million
      in sales) to an estimated 720,000 ($78 million in sales) in 2007. The growth was
      largely driven by the introduction of acamprosate in 2005, which soon became the
      market leader ($35 million in sales). Prescriptions for the two buprenorphine
      formulations increased from 48,000 prescriptions ($5 million in sales) in the
      year of their introduction (2003) to 1.9 million prescriptions ($327 million in
      sales) in 2007. While acamprosate and buprenorphine grew rapidly after market
      entry, overall substance abuse retail medication sales remain small relative to
      the size of the population that could benefit from treatment and relative to
      sales for other medications, such as antidepressants. The extent to which
      substance dependence medications will be adopted by physicians and patients, and
      marketed by industry, remains uncertain.

PMID- 18819760
TI  - Clonality of Enterococcus faecalis associated with amyloid arthropathy in
      chickens evaluated by multilocus sequence typing (MLST).
AB  - The aim of the study was to evaluate the clonality of 21 strains of Enterococcus
      faecalis associated with arthritis and amyloid arthropathy by multilocus sequence
      typing (MLST). The strains originated from five countries. Fifteen of the 21
      strains demonstrated the same sequence type, ST82, including a reference amyloid
      arthropathy strain from the Netherlands. Some of the demonstrated sequence types
      (ST36, ST59 and ST82) have also been described from human clinical samples while
      other types are reported for the first time. The results confirm previous
      observations that outbreaks of amyloid arthropathy seem to be clonally related
      and indicate a wide distribution of the predominant sequence type which was
      demonstrated in four countries in Europe and in the USA.

PMID- 18819761
TI  - Physical therapy reduces insomnia symptoms in postmenopausal women.
AB  - OBJECTIVE: Regular exercise has been highly promoted and recognized as the best
      non-pharmacological treatment for postmenopausal problems. It may also increase
      total sleep time and decrease the latency of sleep onset. One study assessed the
      effects of exercise on sleep symptoms in postmenopausal women. Tworoger et al.
      [Tworoger SS, Yasui Y, Vitiello MV, et al. Effects of a Yarlong moderate
      intensity exercise and stretching intervention on sleep quality in postmenopausal
      women. Sleep 2003;26(7):830-6] observed that increased fitness was associated
      with an improvement in sleep. No studies have been published describing the
      effects of physiotherapeutic treatments for insomnia in postmenopausal women.
      This study examines two cases of symptomatic postmenopausal patients with
      insomnia. The two patients took part in an individual physiotherapeutic treatment
      program that involved one and a half hour sessions twice a week for 6 consecutive
      months. The treatment consisted of segmental and global stretching exercises,
      strengthening exercises, massotherapy and relaxation techniques. Patient 1
      experienced a significant increase in REM sleep and in total sleep efficiency.
      Patient 2 experienced a reduction in sleep latency and an increase in slow wave
      sleep, as shown in the polysomnograph. Both patients reported an overall
      improvement in their condition.

PMID- 18819762
TI  - Unilateral hypoglossal nerve palsy due to neurovascular conflict in a child.
AB  - A neurovascular conflict (NC) consists of a pathological contact between a
      vessel, generally an artery, and the root entry zone of a cranial nerve close to
      the brainstem. Even if NC of the V, VII and IX cranial nerve have been rarely
      described, to the best of our knowledge there is no report about the XII cranial
      nerve NC in the paediatric age. A three-year-old girl presented with right-sided
      tongue atrophy and fasciculation, of one-year-duration, consistent with a
      peripheral lesion of the right XII cranial nerve. Brain MRI and MRA documented a
      marked tortuosity of the vertebrobasilar arteries compressing the brainstem at
      the emergency of the XII cranial nerve, while the CT disclosed a concomitant
      osseous malformation of the cranio-cervical junction. The differential diagnosis
      of a peripheral unilateral cranial nerve palsy should include, even if rare in
      children, a neurovascular conflict. In this case a complete neuroimaging study is
      indicated.

PMID- 18819763
TI  - [Paradoxical embolism and ischemia of the digestive tract].
AB  - The digestive tract is an uncommon location of acute ischemia, especially when
      caused paradoxical embolism. We report the case of a 69-year-old patient
      initially hospitalized for a acute ischemia of the upper limb. Physical
      examination and complementary tests enabled the diagnosis of paradoxical embolism
      with bilateral pulmonary embolism leading to elevated pressure in the pulmonary
      arteries, which opened the oval foramen. The patient also presented ischemia
      involving the digestive trunks, the upper limb and the kidneys. Rapid diagnosis
      is a major challenge in this condition controlling the prognosis of this uncommon
      disease.

PMID- 18819764
TI  - [Bilateral leg compartment syndrome due to severe myonecrosis caused by
      inappropriate use of simvastatin].
AB  - Bilateral leg compartment syndrome due to myonecrosis caused by inappropriate use
      of statins is a rare but potentially fatal complication of this lipid lowering
      medication. We report a case of a 39-year-old woman who presented with suspicious
      critical lower limb ischemia. Subsequently, bilateral leg compartment syndrome
      and myonecrosis developed. The primary cause of myonecrosis was due to misuse of
      simvastatin mistaken by the patient for a weight-reducing drug. Urgent
      fasciotomies were performed and the patient underwent urgent renal replacement
      therapy with continuous hemodialysis for acute renal failure due to
      myoglobinuria. After this complex treatment, the patient was discharged. She
      almost fully recovered with only a residual paresis of the left fibular nerve.
      According to literature, this is a unique case of bilateral compartment syndrome
      and myonecrosis with acute renal failure due to statin overdose leading to acute
      renal failure and bilateral fasciotomy.

PMID- 18819765
TI  - [Prolonged fever of unknown origin in Behcet's disease. Pay attention to
      vessels!].
AB  - Behcet's disease is a systemic vasculitis characterized by the association of
      recurrent oral and genital ulcers to systemic involvements, particularly ocular,
      nervous and vascular manifestations. Contrary to other vasculitis, prolonged
      fever of unknown origin is rare in Behcet's disease. We report a case of a 26
      year-old man presenting prolonged fever for two months. Physical examination
      showed oral, genital ulcers and pseudofolliculitis. The sedimentation rate was
      increased. Chest and abdominal computed tomography revealed thrombus in the
      inferior vena cava and portal vena. Outcome was favorable with glucocorticoid and
      anticoagulant therapy. Prolonged fever occurring during Behcet's disease should
      prompt a search for a vascular injury.

PMID- 18819766
TI  - Bubbles, light, CAD, PET: news in breast imaging.

PMID- 18819767
TI  - Change in contrast enhancement of HCC on 1-month follow-up CT after local
      radiotherapy: an early predictor of final treatment response.
AB  - BACKGROUND: The purpose of this study was to evaluate the change in contrast
      enhancement of HCC on 1-month follow-up CT after local radiotherapy (RT) as an
      early predictor of final treatment response. MATERIALS: Fifty patients who
      underwent local RT for HCCs had both pre-RT and post-RT CT scans including 1
      month follow-up CT. We assessed the final treatment response by using the change
      in maximal tumor size on 6-12-month follow-up CT scan after RT. We also evaluated
      the change in tumor enhancement between pre-RT and 1-month follow-up CT scans.
      RESULTS: A final treatment response was achieved in 27 (54%) of 50 patients, who
      showed either a complete response (n=11) or a partial response (n=16). Compared
      with non-responsive patients (n=23), responsive patients showed a significant
      decrease in tumor enhancement on 1-month follow-up CT after RT in both objective
      and subjective analyses (each P<0.001). CONCLUSION: The change in contrast
      enhancement of HCC seen on the 1-month follow-up CT in patients after local RT
      may be used as an early predictor of final treatment response.

PMID- 18819768
TI  - Quantitative determination of diclofenac sodium in solid dosage forms by FT-Raman
      spectroscopy.
AB  - The FT-Raman quantification of diclofenac sodium in tablets and capsules was
      performed with the help of the partial least squares (PLS), principal component
      regression (PCR) and counter-propagation artificial neural networks (CP-ANN)
      methods. For the analysed tablets, calibration models were built using
      unnormalised spectra and spectra normalised by the intensity of a selected band
      of an internal standard. Different pre-processing methods were applied for the
      capsules. To compare the predictive ability of the models, the relative standard
      errors of prediction (RSEP) were calculated. The 5 x 5 CP-ANN and PLS methods
      gave models of comparable quality, which were usually more efficient than the PCR
      ones. The RSEP error values for the tablets were in the range of 2.4-3.8% for the
      calibration and 2.6-3.5% for the validation data sets and for the three
      procedures applied. For capsules, the RSEP errors were in the range of 0.8-1.9%
      and 1.4-1.7% for the calibration and validation samples, respectively. Five
      commercial products containing 25, 50 or 75 mg of diclofenac sodium per
      tablet/capsule were quantified. Concentrations found from the Raman data analysis
      agree with the results of the reference analysis and correlate strongly with the
      declared values with the recovery of 99.5-101.3%, 99.7-102.0% and 99.9-101.2% for
      the PLS, PCR and CP-ANN methods, respectively. The proposed procedure can be a
      fast and convenient alternative to the standard pharmacopoeial methods of
      diclofenac sodium quantification in solid dosage forms.

PMID- 18819769
TI  - Pharmaceutical applications of vibrational chemical imaging and chemometrics: a
      review.
AB  - The emergence of chemical imaging (CI) has gifted spectroscopy an additional
      dimension. Chemical imaging systems complement chemical identification by
      acquiring spatially located spectra that enable visualization of chemical
      compound distributions. Such techniques are highly relevant to pharmaceutics in
      that the distribution of excipients and active pharmaceutical ingredient informs
      not only a product's behavior during manufacture but also its physical attributes
      (dissolution properties, stability, etc.). The rapid image acquisition made
      possible by the emergence of focal plane array detectors, combined with
      publication of the Food and Drug Administration guidelines for process analytical
      technology in 2001, has heightened interest in the pharmaceutical applications of
      CI, notably as a tool for enhancing drug quality and understanding process.
      Papers on the pharmaceutical applications of CI have been appearing in steadily
      increasing numbers since 2000. The aim of the present paper is to give an
      overview of infrared, near-infrared and Raman imaging in pharmaceutics. Sections
      2 and 3 deal with the theory, device set-ups, mode of acquisition and processing
      techniques used to extract information of interest. Section 4 addresses the
      pharmaceutical applications.

PMID- 18819770
TI  - Role of glutathione S-transferase Pi in cisplatin-induced nephrotoxicity.
AB  - One of the dose-limiting toxicities of cisplatin is nephrotoxicity. Renal
      toxicity is localized to quiescent proximal tubule cells, where the formation of
      DNA-adducts cannot account for the dose-limiting toxicity. Our earlier results
      have shown that a glutathione conjugate of cisplatin is metabolized to a
      nephrotoxicant via gamma-glutamyl transpeptidase (GGT) and a cysteine S-conjugate
      beta-lyase. The present study was designed to evaluate the potential role of
      glutathione S-transferase Pi (GSTP) in the initial steps of the bioactivation of
      cisplatin. Wild-type mice and mice deficient in both murine GSTP genes (GstP1/P2)
      were treated with cisplatin. Toxicity in both male and female mice was evaluated
      5 days after treatment and renal damage was most severe in wild-type male mice.
      Wild-type males have approximately 10-fold higher levels of GSTP expression in
      the liver than females, suggesting that hepatic GSTP in the wild-type males
      contributed to the formation of the nephrotoxic platinum-glutathione conjugate.
      In GstP1/P2 null mice the gender difference in toxicity was eliminated. Our data
      show that GSTP expression is a determinant in cisplatin-induced nephrotoxicity
      and its levels contribute to sex-dependent differences.

PMID- 18819771
TI  - [Pregnancy and vasculitides].
AB  - Systemic vasculitides, like Takayasu's arteritis, polyarteritis nodosa, Wegener's
      granulomatosis, Churg-Strauss syndrome, Henoch-Schonlein purpura, or Behcet's
      disease can affect women of child-bearing years. The rarity of these
      vasculitides, their frequent fatal outcomes until recent years, and the use of
      toxic immunosuppressants to treat patients, contra-indicating pregnancy and/or
      potentially inducing hypofertility or sterility, explain the few pregnancies
      reported in the literature so far. Notably, it does not seem that pregnancy has a
      major impact on vasculitis outcome, in contrast with systemic lupus
      erythematosus, but a specialized management of these pregnant patients is
      mandatory. There are some reported cases of vasculitis revealed during pregnancy.
      Even though some of these pregnant patients had a severe disease and died, most
      of them had a favourable outcome, and a living inborn, providing prompt care and
      adequate treatment. When vasculitis is already known and treated, pregnancy
      should at best be planned, when the disease is in sustained remission and all
      toxic immunosuppressants have been stopped for months. Vasculitis sequella, like
      hypertension, renal insufficiency, or asthma, must also be taken into account,
      monitored and appropriately managed throughout the pregnancy and a few weeks
      following delivery. In case of vasculitis' flare during pregnancy, potential
      treatments include corticosteroids, intravenous immunoglobulins, azathioprine,
      plasma exchanges, and, for limited skin manifestations or Behcet's disease,
      hydroxychloroquine or colchicine. Importantly, when the disease is severe, a
      delay in the prescription of a stronger, immunosuppressant, chiefly intravenous
      cyclophosphamide, can be more detrimental, although being potentially toxic, for
      both the mother and the foetus than an ineffective and/or inappropriate regimen
      with less active drugs. Safety data on biologics, like rituximab, for pregnant
      women are very sparse to date and their use is therefore not recommended, unless
      confronted with a severe and refractory disease, and after referring to a
      specialized center for vasculitides.

PMID- 18819772
TI  - [Rheumatoid arthritis and pregnancy].
AB  - During pregnancy, oestrogen and progesterone levels are increased. Consequently
      the initial predominant immune cellular response (Th1 type) is decreased, whereas
      humoral response (Th2 type) is increased. Due to this switch, a lot of Th2 anti
      inflammatory cytokines IL-4 and IL-10 are synthesized. During the last months of
      pregnancy Treg lymphocytes level is elevated leading to overexpression of IL-4
      and IL-10. Due to these mechanisms, reduce disease activity of rheumatoid
      arthritis (RA) occurred. Impaired fertility has not been demonstrated in women
      with RA. However, some studies suggest that polyarthritis could induced a reduced
      weight at birth and more frequent pregnancy and delivery complications.
      Methotrexate and biotherapies have demonstrated no effect on fertility; however
      these drugs must be stopped before conception for a period equal to seven fold of
      the half live of the molecule. No teratogenic effect are known for sulfazalasine
      and hydroxychloroquine; these drugs could be used during pregnancy. It is also
      the same for ciclosporine, which used is quite unfrequent in RA. Methotrexate is
      teratogenic in animal models and is forbidden during pregnancy. For leflunomide
      which is metabolised in A771726, highly teratogenic, a washout period of 3,5
      months is necessary. All commercially available TNFalpha inhibitors are
      classified by the food and Drug Administration as pregnancy risk category B: no
      adverse pregnancy adverse effects have been observed in animal studies, but there
      have been insufficient controlled human studies. The published experiences with
      TNFalpha inhibition in pregnancy is limited to some case reports and ongoing
      registry. More recently some cases of Vater syndromes (polymalformations) were
      possibly related to TNFalpha blocking agents. Such treatment must be avoided
      during pregnancy. Only few case reports are published concerning rituximab use
      during pregnancy. No data have been found for abatacept.

PMID- 18819774
TI  - Frequency and severity of the symptoms of irritable bowel syndrome across the
      anxiety disorders and depression.
AB  - High rates of irritable bowel syndrome (IBS) symptoms have been reported in
      individuals diagnosed with anxiety and depressive disorders. However, most
      studies have investigated these relations in a single disorder, rather than a
      heterogeneous group of patients, thereby not allowing for comparisons across
      anxiety disorders and depression, or for considering the effects of comorbidity.
      Thus, the present study investigated the symptoms of IBS in a diverse group of
      patients (N=357) by administering questionnaires and a diagnostic interview. A
      high frequency of IBS symptoms was found in patients with panic disorder,
      generalized anxiety disorder, and major depressive disorder. However, the
      frequency of IBS symptoms in patients with social anxiety disorder, specific
      phobia, and obsessive-compulsive disorder was comparable to rates found in
      community samples. In addition, anxiety sensitivity and illness attitudes and
      intrusiveness were predictive of elevated IBS symptomatology. Together, these
      findings emphasize the role physiological symptoms of anxiety and worry in the co
      occurrence of the anxiety disorders and IBS.

PMID- 18819775
TI  - Summary of the 1st Schizophrenia International Research Society Conference oral
      sessions, Venice, Italy, June 21-25, 2008: the rapporteur reports.
AB  - The Schizophrenia International Research Society held its first scientific
      conference in Venice, Italy, June 21 to 25th, 2008. A wide range of controversial
      topics were presented in overlapping and plenary oral sessions. These included
      new genetic studies, controversies about early detection of schizophrenia and the
      prodrome, treatment issues, clinical characteristics, cognition, neuropathology
      and neurophysiology, other etiological considerations, substance abuse co
      morbidity, and animal models for investigating disease etiology and for use as
      targets in drug studies. Young investigators in the field were awarded travel
      grants to participate in the congress and one of their roles was to summarize the
      oral sessions and subsequent discussions. The reports that follow are the
      culmination of this work produced by 30 young investigators who attended the
      congress. It is hoped that these summaries will be useful synopses of what
      actually occurred at the congress for those who did not attend each session or
      were unable to be present. The abstracts of all presentations, as submitted by
      the authors a few months prior, were previously published as supplement 2 to
      volume 102/1-3, June 2008.

PMID- 18819776
TI  - Evaluation of the activity of 16 medicinal plants against Neisseria gonorrhoeae.
AB  - 50% Ethanolic extracts of various parts of 16 medicinal plants were evaluated for
      potential activity against clinical isolates and WHO strains of Neisseria
      gonorrhoeae, including multidrug-resistant (MDR) strains. Activity was calculated
      as percentage inhibition in comparison with penicillin and ciprofloxacin and
      strains were categorised as less sensitive, sensitive or highly sensitive to the
      extracts. The extracts caused differential inhibition of N. gonorrhoeae, with
      greater inhibition of the MDR strains. Among the extracts tested, 60% exhibited
      high activity whereas 20% showed moderate activity and 20% had little activity
      against N. gonorrhoeae.

PMID- 18819777
TI  - Non-staphylococcal Gram-positive bacteraemia without a known source.
AB  - This paper reviews bacteraemia without a known source caused by Gram-positive
      cocci, excluding staphylococci. These organisms include streptococci of groups A,
      B, C and G. Bacteraemia caused by nutritionally variant streptococci is also
      discussed.

PMID- 18819779
TI  - Zolpidem-induced amnesia and somnambulism: rare occurrences?
AB  - Zolpidem, a non-benzodiazepine hypnotic of the imidazopyridine class, is very
      effective in treating insomnia with previous claims of little adverse effects.
      However, zolpidem-induced somnambulism and amnesic sleep-related behavioral
      problems were begun to be reported in literature but no systemic investigation
      has been undertaken in non-Western cultures. In our current retrospective survey,
      5.1% (13 out of 255) of Taiwanese patients reported change in sleep-related
      behavior as adverse effects. This serves as a reminder for clinicians to inquire
      regarding any unusual behavior of parasomniac activities when prescribing
      zolpidem.

PMID- 18819780
TI  - Preferred orientation of albumin adsorption on a hydrophilic surface from
      molecular simulation.
AB  - In general, non-specific protein adsorption follows a two-step procedure, i.e.
      first adsorption onto a surface in native form, and a subsequent conformational
      change on the surface. In order to predict the subsequent conformational change,
      it is important to determine the preferred orientation of an adsorbed protein in
      the first step of the adsorption. In this work, a method based on finding the
      global minimum of the interaction potential energy of an adsorbed protein has
      been developed to delineate the preferred orientations for the adsorption of
      human serum albumin (HSA) on a model surface with a hydrophilic self-assembled
      monolayer (SAM). For computational efficiency, solvation effects were greatly
      simplified by only including the dampening of electrostatic effects while
      neglecting contributions due to the competition of water molecules for the
      functional groups on the surface. A contour map obtained by systematic rotation
      of a molecule in conjunction with perpendicular motion to the surface gives the
      minimum interaction energy of the adsorbed molecule at various adsorption
      orientations. Simulation results show that for an -OH terminated SAM surface, a
      "back-on" orientation of HSA is the preferred orientation. The projection area of
      this adsorption orientation corresponds with the "triangular-side-on" adsorption
      of a heart shaped HSA molecule. The method proposed herein is able to provide
      results which are consistent with those predicted by Monte Carlo (MC) simulations
      with a substantially less computing cost. The high computing efficiency of the
      current method makes it possible to be implemented as a design tool for the
      control of protein adsorption on surfaces; however, before this can be fully
      realized, these methods must be further developed to enable interaction free
      energy to be calculated in place of potential energy, along with a more realistic
      representation of solvation effects.

PMID- 18819781
TI  - Importance of LPS structure on protein interactions with Pseudomonas aeruginosa.
AB  - Atomic force microscopy (AFM) was used to quantify the adhesion forces between
      Pseudomonas aeruginosa PAO1 and AK1401, and a representative model protein,
      bovine serum albumin (BSA). The two bacteria strains differ in terms of the
      structure of their lipopolysaccharide (LPS) layers. While PAO1 is the wild-type
      expressing a complete LPS and two types of saccharide units in the O-antigen
      (A(+) B(+)), the mutant AK1401 expresses only a single unit of the A-band
      saccharide (A(+) B(-)). The mean adhesion force (F(adh)) between BSA and AK1401
      was 1.12 nN, compared to 0.40 nN for F(adh) between BSA and PAO1. In order to
      better understand the fundamental forces that would control bacterial-protein
      interactions at equilibrium conditions, we calculated interfacial free energies
      using the van Oss-Chaudhury-Good (VCG) thermodynamic modeling approach. The
      hydrogen bond strength was also calculated using a Poisson statistical analysis.
      AK1401 has a higher ability to participate in hydrogen bonding with BSA than does
      PAO1, which may be because the short A-band and absence of B-band polymer allowed
      the core oligosaccharides and lipid A regions to be more exposed and to
      participate in hydrogen and chemical bonding. Interactions between PAO1 and BSA
      were weak due to the dominance of neutral and hydrophilic sugars of the A-band
      polymer. These results show that bacterial interactions with protein-coated
      surfaces will depend on the types of bonds that can form between bacterial
      surface macromolecules and the protein. We suggest that strategies to prevent
      bacterial colonization of biomaterials can focus on inhibiting these bonds.

PMID- 18819782
TI  - [Postoperative complications of laparoscopic cholecystectomy in children with
      homozygous sickle cell disease: experience of a French pediatric hospital].

PMID- 18819783
TI  - [Congenital atrichia with cysts in two sisters].

PMID- 18819784
TI  - [Accidental acute poisonings in children at pediatric ward of Kara Teaching
      Hospital (Togo)].

PMID- 18819785
TI  - Differences in traditional and emerging cardiovascular risk factors of subjects
      discordantly classified by metabolic syndrome definitions of the International
      Diabetes Federation and the National Cholesterol Education Program.
AB  - BACKGROUND AND AIM: Several working definitions of metabolic syndrome have been
      proposed for clinical use. However, individuals can be discordantly classified as
      having or not having metabolic syndrome depending on the choice of one or another
      definition. This study compared the cardiovascular risk profile of subjects
      concordantly and discordantly diagnosed by the criteria of the National
      Cholesterol Education Program (NCEP) and the criteria of the International
      Diabetes Federation (IDF). METHODS AND RESULTS: Nine hundred and twenty-nine non
      diabetic adult subjects belonging to a cross-sectional population-based study in
      Gran Canaria island (Spain) were assessed. Participants completed a questionnaire
      and underwent physical examination, fasting blood analyses, and a standardized
      oral glucose tolerance test. Two hundred and four subjects (22%) had metabolic
      syndrome according to both definitions, 31 (3.3%) only by the IDF criteria, and 5
      (0.5%) only by the NCEP criteria. Participants fulfilling both proposals showed
      more adverse age and sex-adjusted measures of BMI, waist, HDL cholesterol,
      triglycerides, post-load glucose, HOMA-IR and plasminogen inhibitor activator-1
      (PAI-1) than individuals exclusively satisfying the IDF criteria. Moreover, in
      contrast to subjects meeting both criteria, those that fulfilled only the IDF
      criteria had levels of BMI, waist, total and HDL cholesterol, post-load glucose,
      glycated HbA1c, C-reactive protein, PAI-1 and fibrinogen not significantly
      different from those observed in subjects without metabolic syndrome. CONCLUSION:
      The IDF definition identifies a surplus of individuals whose cardiovascular risk
      profile, particularly regarding to some non-traditional cardiovascular risk
      factors, is less adverse than that observed in subjects also diagnosed by the
      NCEP definition.

PMID- 18819786
TI  - Marie-Francois Xavier Bichat (1771-1802) and his contributions to the foundations
      of pathological anatomy and modern medicine.
AB  - Marie-Francois Xavier Bichat (1771-1802) was a prominent French anatomist during
      a time of revolution and one of the founders of French scientific medicine. He
      conducted several experimental studies, which laid the foundation for modern
      physiology. Based on autopsy findings, Bichat introduced 21 tissues as the basic
      elements of organs. His name is carried on by several eponyms in anatomy and
      histology; Bichat's fossa (pterygopalatine fossa), Bichat's protuberance (buccal
      fat pad), Bichat's foramen (cistern of the vena magna of Galen), Bichat's
      ligament (lower fasciculus of the posterior sacroiliac ligament), Bichat's
      fissure (transverse fissure of the brain) and Bichat's tunic (tunica intima
      vasorum). This paper deals with the life and works of this early pioneer in
      anatomy and physiology.

PMID- 18819787
TI  - Effect of weight change on asthma-related health outcomes in patients with severe
      or difficult-to-treat asthma.
AB  - OBJECTIVE: To evaluate the effects of weight change on asthma control, asthma
      related quality of life, number of steroid bursts, and exacerbation of asthma
      symptoms in a population of adult patients with severe or difficult-to-treat
      asthma who participated in The Epidemiology and Natural History of Asthma:
      Outcomes and Treatment Regimens (TENOR) study. METHODS: We categorized 2396 TENOR
      patients > or = 18 years into three groups (> or = 5 lb loss, stable, > or = 5 lb
      gain), based on a +/-5 lb (2.27 kg) difference between baseline and 12-month
      follow-up weight. We used proportional odds and logistic regression models to
      evaluate the effect of weight change on Asthma Therapy Assessment Questionnaire
      (ATAQ) and Asthma Quality of Life Questionnaire (AQLQ) scores, exacerbations, and
      steroid bursts at the 12-month follow-up. RESULTS: Asthma patients who gained >
      or = 5 lb (2.27 kg) during the 12-month interval between baseline and follow-up
      reported poorer asthma control (adjusted odds ratio [OR]: 1.22; 95% confidence
      interval [CI]: 1.01-1.49; p=0.04), worse quality of life (least square means: 
      0.18; 95% CI: -0.30 to -0.06; p=0.003), and a greater number of steroid bursts
      (OR: 1.31; CI: 1.04-1.66; p=0.02) than patients who maintained their baseline
      weight or lost > or = 5 lb (2.27 kg). CONCLUSION: Increased weight is associated
      with worse asthma-related health outcomes. Strategies to prevent weight gain
      could help patients achieve better asthma control and improve asthma-related
      quality of life.

PMID- 18819788
TI  - Suppressed signal transduction in the bronchial epithelium of patients with
      systemic sclerosis.
AB  - INTRODUCTION: Systemic sclerosis (SSc) is an autoimmune disorder, which
      frequently affects the lungs, with manifestations of interstitial lung disease
      (ILD) with lung fibrosis and of pulmonary hypertension. The pathogenesis remains
      largely unrecognised. OBJECTIVE: The aim of this study was to elucidate the
      inflammation in the bronchial mucosa in patients with SSc. SUBJECTS AND METHODS:
      Twenty-three subjects diagnosed with SSc participated. Twelve of the SSc patients
      showed signs of ILD, four were smokers and seven were treated with oral
      corticosteroids. Seventeen non-smoking, age- and sex-matched healthy subjects
      served as controls. Bronchoscopy was performed to sample endobronchial mucosal
      biopsies, which were immunohistochemically stained using a panel of antibodies
      against inflammatory markers. RESULTS: The number of neutrophils was
      significantly elevated in the submucosa of SSc patients, regardless of ILD, or
      whether the subject was smoking or using oral corticosteroids. No up-regulation
      of neutrophil chemoattractants or cytokines was seen in the bronchial epithelium.
      The signal transduction pathways and adhesion molecule expression tended to be
      suppressed or unchanged in SSc patients compared with controls. CONCLUSION: It is
      concluded that SSc is associated with a chronic neutrophilic inflammation in the
      bronchial mucosal, with signs of suppressed signal transduction, regardless of
      the presence of interstitial lung disease.

PMID- 18819789
TI  - Application of parylene-coated quartz crystal microbalance for on-line real-time
      detection of microbial populations.
AB  - A novel technique of applying a quartz crystal microbalance (QCM) sensor to the
      on-line real-time detection of microbial populations is described. The pQCM
      sensor was fabricated by depositing di-para-xylene (parylene) over the entire
      surface of a QCM sensor through a chemical vapor deposition (CVD) process. An
      electrically insulated film of parylene on the QCM sensor enabled the operation
      of the sensor in the liquid environment, and the resonance frequency of the pQCM
      sensor set in the medium of a cultivation flask shifted in response to the
      microbial population. The effects of pH, conductivity, and viscosity of the
      medium on the frequency shift of the pQCM sensor were investigated. Ignorable
      responses (less than 1% at 10(3)cells) were obtained during an incubation cycle.
      The detection limit of the pQCM sensor was identified as 10(2) cells ml(-1) with
      a frequency shift of around 2 x 10(3)Hz. The cell numbers of Escherichia coli
      cultivated in both the YEM medium and whole milk were detected. A satisfactory
      correlation (r(2)=0.95) was obtained between the cell number and the response of
      the pQCM sensor. Experimental results suggest that the pQCM described here is
      applicable to the continuous long-term detection of microbial populations during
      a fermentation process.

PMID- 18819790
TI  - A novel electrochemical immunosensor based on ordered Au nano-prickle clusters.
AB  - In this paper, we report a kind of ordered 3D Au nano-prickle clusters by
      directly electrodeposited on glassy carbon electrode utilizing the spatial
      obstruction/direction of the polycarbonate membrane. The proposed 3D nanoclusters
      are applied to fabricate a sandwich-type electrochemical immunosensor with human
      IgG as a model analyte. The electrodeposited Au nanoclusters build direct
      electrical contact and immobilization interface for protein molecules, which do
      not need post-modification and positioning. Scanning electron microscopy, cyclic
      voltammetry and alternating current impedance spectroscopy were used to
      investigate the properties of the modified interface. The deposited Au
      nanoclusters are stable with good biocompatibility, large specific surface area
      and high electron exchange capability. Under the optimized experimental
      conditions, a wide linear range from 1.0 to 10000.0 ng/mL was reached with a
      detection limit of 0.5 ng/mL. The calibration curve fits a second-order
      polynomial equation very well (R(2)=0.9914). The developed immunosensor based on
      Au nano-prickle clusters possesses advantages such as simple fabrication, fast
      response, low detection limit, wide linear range, easy regeneration, excellent
      reproducibility and long stability. To our knowledge, the Au nanostructure of
      special ordered 3D nano-prickle clusters is new for electrochemical immunosensor.

PMID- 18819791
TI  - How to interpret the relative survival ratios of cancer patients.
AB  - It is common in population-based cancer registries to use the relative survival
      ratio to estimate patients' probabilities of surviving if their cancer were the
      only cause of death. Results from the recently proposed new methods of age
      standardisation can be interpreted as ratios between the observed and expected
      survival proportions. Like the non-standardised ratios, these age-standardised
      relative survival ratios have, however, the desired probability interpretation
      only under a specific condition. The condition involved is the survival with
      respect to other causes up to the given point of follow-up. With different
      lengths of follow-up, this condition is also different. As a consequence, the non
      standardised relative survival ratios and those standardised with the two newest
      methods produce, for different lengths of follow-up, mutually incomparable
      estimates with respect to age. Not accounting for this may, for example, lead to
      erroneous conclusions about the cure of the patients. The traditional method of
      age-standardisation does not have this problem of incomparability. Results of
      relative survival analyses of data from the Finnish Cancer Registry are used to
      illustrate this issue. To avoid overinterpretation and confusion, the different
      interpretations of the relative survival ratios, both non-standardised and age
      standardised, must be known. For example, the very popular cumulative relative
      survival curves, consisting of consecutive cumulative relative survival ratios,
      should not be produced for the non-standardised ratios or for ratios age
      standardised with the two newest methods. In practical applications, it is
      crucial to know which method of standardisation, and not only which standard
      population, has been in use.

PMID- 18819792
TI  - Phase II study on gemcitabine in recurrent and/or metastatic adenoid cystic
      carcinoma of the head and neck (EORTC 24982).
AB  - BACKGROUND: This phase II study was conducted to determine the antitumour
      activity of gemcitabine in adenoid cystic carcinoma (ACC). PATIENTS AND METHODS:
      Patients with progressive and/or symptomatic, recurrent and/or metastatic ACC
      were treated with gemcitabine 1250 mg/m(2) intravenous (i.v.) on days 1 and 8 of
      each 21-day cycle. Each cycle was repeated every 3 weeks in the absence of
      disease progression for a minimum of four cycles and a maximum of 12 cycles.
      RESULTS: Among 21 ACC patients, there were no objective responses. Eleven
      patients had a stable disease, of which ten patients for more than 6 months, and
      eight had a progressive disease after 4 cycles. Gemcitabine was well tolerated by
      most patients. CONCLUSION: We conclude that gemcitabine is not an active drug in
      ACC.

PMID- 18819793
TI  - Continuous biosynthesis of biodiesel from waste cooking palm oil in a packed bed
      reactor: optimization using response surface methodology (RSM) and mass transfer
      studies.
AB  - This study aimed to develop an optimal continuous procedure of lipase-catalyzes
      transesterification of waste cooking palm oil in a packed bed reactor to
      investigate the possibility of large scale production further. Response surface
      methodology (RSM) based on central composite rotatable design (CCRD) was used to
      optimize the two important reaction variables packed bed height (cm) and
      substrate flow rate(ml/min) for the transesterification of waste cooking palm oil
      in a continuous packed bed reactor. The optimum condition for the
      transesterification of waste cooking palm oil was as follows: 10.53 cm packed bed
      height and 0.57 ml/min substrate flow rate. The optimum predicted fatty acid
      methyl ester (FAME) yield was 80.3% and the actual value was 79%. The above
      results shows that the RSM study based on CCRD is adaptable for FAME yield
      studied for the current transesterification system. The effect of mass transfer
      in the packed bed reactor has also been studied. Models for FAME yield have been
      developed for cases of reaction control and mass transfer control. The results
      showed very good agreement compatibility between mass transfer model and the
      experimental results obtained from immobilized lipase packed bed reactor
      operation, showing that in this case the FAME yield was mass transfer controlled.

PMID- 18819794
TI  - Itk kinase inhibitors: initial efforts to improve the metabolical stability and
      the cell activity of the benzimidazole lead.
AB  - Previously, we reported a series of novel benzimidazole based Itk inhibitors that
      exhibited excellent enzymatic potency and selectivity but low microsomal
      stability. Employing a structure based approach a new series of inhibitors with
      comparable potency and selectivity to the original series and with a potential
      for improved microsome stability was identified.

PMID- 18819795
TI  - Catalytic site-selective synthesis and evaluation of a series of erythromycin
      analogs.
AB  - The generation of a series of analogs of erythromycin A (EryA, 2) is described.
      In this study, we compared two peptide-based catalysts-one originally identified
      from a catalyst screen (5) and its enantiomer (ent-5)-for the selective
      functionalization of EryA. The semi-synthetic analogs were subjected to MIC
      evaluation with two bacterial strains and compared to unfunctionalized EryA.

PMID- 18819796
TI  - A novel monoacylglycerol lipase inhibitor with analgesic and anti-inflammatory
      activity.
AB  - A variety of long chain 1,2-diamines and related compounds were synthesized and
      tested for their activity on fatty acid amide hydrolase (FAAH) and
      monoacyglycerol lipase (MGL). (2S,9Z)-Octadec-9-ene-1,2-diamine selectively
      inhibits MGL (K(i) 21.8 microM) without significantly affecting FAAH. This
      compound exhibited interesting in vivo analgesic and anti-inflammatory
      properties, suggesting that selective inhibitors of MGL may be valuable novel
      agents for the treatment of inflammatory pain.

PMID- 18819797
TI  - (3R)-3-amino-4-(2,4,5-trifluorophenyl)-N-{4-[6-(2-methoxyethoxy)benzothiazol-2
      yl]tetrahydropyran-4-yl}butanamide as a potent dipeptidyl peptidase IV inhibitor
      for the treatment of type 2 diabetes.
AB  - Novel series of 3-amino-N-(4-aryl-1,1-dioxothian-4-yl)butanamides and 3-amino-N
      (4-aryltetrahydropyran-4-yl)butanamides were synthesized and evaluated as
      dipeptidyl peptidase IV (DPP-IV) inhibitors. Derivatives incorporating the 6
      substituted benzothiazole group showed highly potent DPP-IV inhibitory activity.
      Oral administration of (3R)-3-amino-4-(2,4,5-trifluorophenyl)-N-{4-[6-(2
      methoxyethoxy)benzothiazol-2-yl]tetrahydropyran-4-yl}butanamide (12u) reduced
      blood glucose excursion in an oral glucose tolerance test.

PMID- 18819798
TI  - Fluorination of mammalian cell surfaces via the sialic acid biosynthetic pathway.
AB  - Metabolic oligosaccharide engineering has been employed to introduce fluorine
      containing groups onto mammalian cell surfaces. Incubation of HeLa, Jurkat, and
      HL60 cells in culture with fluorinated sialic acid and mannosamine analogues
      resulted in cell-surface presentation of fluorinated glycans. Metabolic
      conversion of fluorinated precursors was detected and quantified by DMB
      derivatization and HPLC ESI-MS analysis. Between 7% and 72% of total membrane
      associated sialosides were fluorinated, depending on the precursor used and the
      cell type. Fluorination of mammalian cell surfaces provides a means for
      introducing a bioorthogonal surface for modulating noncovalent interactions such
      as those involved in cell adhesion.

PMID- 18819799
TI  - Discovery, SAR and X-ray structure of 1H-benzimidazole-5-carboxylic acid
      cyclohexyl-methyl-amides as inhibitors of inducible T-cell kinase (Itk).
AB  - A series of novel potent benzimidazole based inhibitors of interleukin-2 T-cell
      kinase (Itk) were prepared. In this report, we discuss the structure-activity
      relationship (SAR), selectivity, and cell-based activity for the series. We also
      discuss the SAR associated with an X-ray structure of one of the small-molecule
      inhibitors bound to ITK.

PMID- 18819800
TI  - Dishevelled links basal body docking and orientation in ciliated epithelial
      cells.
AB  - Some epithelia contain cells with multiple motile cilia that beat in a concerted
      manner. New tools and experimental systems have facilitated molecular studies of
      cilium biogenesis and the coordinated planar polarization of cilia that leads to
      their concerted motility. A recent elegant study using embryonic frog epidermis
      demonstrates that Dishevelled, a key regulator of both the Wnt-beta-catenin and
      planar cell polarity pathways, controls both the docking and planar polarization
      of ciliary basal bodies.

PMID- 18819801
TI  - Genomes and knowledge - a questionable relationship?
AB  - The availability of bacterial genome sequences has ushered in an era of post
      genomic research - accelerating and often enabling molecular genetic analyses.
      For bacteriologists focussing on an individual bacterium, comparing genomes has
      also led to a greater understanding of their favoured organism through
      contextualization. But how does the value of such contextualization vary with the
      number of available genomes? It seems that for most genome metrics, comparison
      against approximately 100 genomes is sufficient, with comparison against further
      genomes not considerably affecting the contextual knowledge gained. It appears
      that quality, rather than quantity, might be the most important factor when
      comparing genomes.

PMID- 18819802
TI  - Subcellular alterations that lead to diarrhea during bacterial pathogenesis.
AB  - Pathogenic microorganisms routinely exploit host cellular functions for their
      benefit. These alterations often enhance the survival and/or dissemination of the
      pathogen. However, these effects on the host can be quite debilitating.
      Consequently, an in-depth understanding of the molecular mechanisms employed by
      pathogens to manipulate their hosts is crucial. One of the common host phenotypes
      elicited by enteric pathogens is the generation of diarrhea. Here, we overview
      the current advances in understanding strategies used by bacterial pathogens to
      cause diarrheal diseases and discuss how the coordination of various subcellular
      events can influence disease progression.

PMID- 18819803
TI  - Moving targets: rapid evolution of oomycete effectors.
AB  - Plant pathogenic microbes secrete proteins known as effectors, which enter the
      cytoplasm of plant cells and suppress host defences. Known effectors in oomycete
      pathogens possess an RXLR-EER motif in their amino acid sequence that is
      necessary for transport of the effector into a host plant cell. A large number of
      putative effectors have now been identified in oomycete genomes, the sequences of
      which show evidence of diversifying selection at their C terminus. Here, we
      describe recent progress in characterizing RXLR-EER effectors and discuss why so
      many of these rapidly evolving proteins are encoded by the genomes of plant
      pathogenic oomycetes.

PMID- 18819804
TI  - Pathodiagnostic parameters for meningioma grading.
AB  - Meningiomas are usually slow-growing benign tumors, for which complete removal
      can be difficult and recurrence is an issue. In this study the relationship
      between pathodiagnostic parameters, histological grade, and MIB-1 monoclonal
      antibody expression in meningioma diagnosed over 10 years in Shohada Hospital,
      Tehran, was assessed. All cases were re-evaluated according to the latest World
      Health Organization (WHO) Classification. Between January 1997 and December 2006,
      a total of 4885 intracranial tumors were diagnosed at Shohada Hospital, 378
      (7.74%) of which were meningiomas. All slides stained with hematoxylin and eosin
      were reviewed by two independent pathologists and all the diagnoses reconfirmed;
      histological anaplasia was classified according to the grading of the WHO Working
      Group 2000 as benign (Grade I), atypical with incipient signs of anaplasia (Grade
      II), or overtly anaplastic (Grade III). The mean age of patients with meningiomas
      was 49.11+/-12.99 years (range 6-78 years, median=50); females outnumbered males
      by a ratio of 1.7 to 1. Presenting symptoms were headache/vertigo (66.7%) and
      epilepsy (28.5%). Convexity meningiomas were most common, followed by meningiomas
      of the sphenoid ridge and cerebellopontine angle. There was no relationship
      between the location of the tumor and the histopathological features. The
      association between mitotic rate, increased cellularity, nucleo-cytoplasmic
      ratio, and sheet-like spreading was especially strong. Histopathological study of
      completely resected meningiomas showed that loss of architecture, frequent
      mitotic figures, a high cellularity, increased nucleo-cytoplasmic ratio, a
      prominent nucleolus, brain invasion, and necrosis were correlated with the grade
      of the meningiomas. Overall, the mitotic count was the most important marker for
      tumor grade.

PMID- 18819805
TI  - Untangling the glutamate dehydrogenase allosteric nightmare.
AB  - Glutamate dehydrogenase (GDH) is found in all living organisms, but only animal
      GDH is regulated by a large repertoire of metabolites. More than 50 years of
      research to better understand the mechanism and role of this allosteric network
      has been frustrated by its sheer complexity. However, recent studies have begun
      to tease out how and why this complex behavior evolved. Much of GDH regulation
      probably occurs by controlling a complex ballet of motion necessary for catalytic
      turnover and has evolved concomitantly with a long antenna-like feature of the
      structure of the enzyme. Ciliates, the 'missing link' in GDH evolution, might
      have created the antenna to accommodate changing organelle functions and was
      refined in humans to, at least in part, link amino acid catabolism with insulin
      secretion.

PMID- 18819806
TI  - Arthrogryposis and congenital absence of the anterior cruciate ligament: a case
      report.
AB  - Arthrogryposis is a non-progressive disorder with congenitally soft tissue
      contractures affecting two or more joints. It can be sporadic, or inherited in an
      autosomal dominant or recessive fashion. Typically, in the upper limb, the
      shoulder is in adduction and internal rotation, the elbow is in extension with a
      lack of skin crease, and the wrist is in flexion with ulnar deviation. In the
      lower limb, the hip is in flexion, abduction and external rotation, the knee is
      contracted, with resistant clubfoot and congenital vertical talus. We report a
      case of a man and his son with a new form of autosomal dominant arthrogryposis
      associated with congenital absences of the anterior cruciate ligament. This
      manifestation of arthrogryposis has not been described previously.

PMID- 18819807
TI  - How to address the patella in revision total knee arthroplasty.
AB  - Patellar issues need to be carefully addressed during any revision TKA and the
      surgeon often faces the question of what to do with the patella at the time of
      revision. The choice of treatment is often made by balancing what is technically
      feasible with the risk of potential complications and takes into account the
      reason for the revision, the type of implant (i.e., metal-backing or all
      polyethylene), the duration of implantation, the fixation, the stability, the
      sterilization technique, the wear, the presence of osteolysis, the compatibility
      with the femoral component, and most importantly the remaining bone stock. The
      various treatment options then include retention of the patellar component,
      revision of the patellar component, removal of the component with retention of
      the patellar bony shell (patelloplasty or resection arthroplasty), excision of
      the patella (partial or total patellectomy), secondary resurfacing, and
      reconstruction/augmentation of the patellar bone stock. Isolated patellar
      revision is associated with a high complication rate and recurrent failure when
      poor patellar tracking, incongruent designs and malalignment of the femoral and
      tibial components exist. Retention of a well-fixed all-PE (non-oxidized) patella
      is advocated where possible and revision of metal-backed patella is recommended
      (unless well fixed with poor bone stock). In the situation of a deficient
      patella, patelloplasty, augmentation procedures and very rarely patellectomy are
      other viable options.

PMID- 18819808
TI  - In vitro inhibition of salicylic acid derivatives on human cytosolic carbonic
      anhydrase isozymes I and II.
AB  - The inhibition of two human cytosolic carbonic anhydrase (hCA, EC 4.2.1.1)
      isozymes, hCA I and II, with a series of salicylic acid derivatives was
      investigated by using the esterase method with 4-nitrophenyl acetate as
      substrate. IC(50) values for sulfasalazine, diflunisal, 5-chlorosalicylic acid,
      dinitrosalicylic acid, 4-aminosalicylic acid, 4-sulfosalicylic acid, 5
      sulfosalicylic acid, salicylic acid, acetylsalicylic acid (aspirin) and 3
      metylsalicylic acid were of 3.04 microM, 3.38 microM, 4.07 microM, 7.64 microM,
      0.13 mM, 0.29 mM, 0.42 mM, 0.56 mM, 2.71 mM and 3.07 mM for hCA I and of 4.49
      microM, 2.70 microM, 0.72 microM, 2.80 microM, 0.75 mM, 0.72 mM, 0.29 mM, 0.68
      mM, 1.16 mM and 4.70 mM for hCA II, respectively. Lineweaver-Burk plots were also
      used for the determination of the inhibition mechanism of these substituted
      phenols, most of which were noncompetitive inhibitors with this substrate. Some
      salicylic acid derivatives investigated here showed effective hCA I and II
      inhibitory activity, and might be used as leads for generating enzyme inhibitors
      eventually targeting other isoforms which have not been assayed yet for their
      interactions with such agents.

PMID- 18819809
TI  - Simplified fast and high yielding automated synthesis of [18F]fluoroethylcholine
      for prostate cancer imaging.
AB  - (11)C- and (18)F-labeled choline analogues are successful tracers for prostate
      cancer imaging using positron emission tomography (PET). Due to the practical
      advantages of the longer-living radioisotope (18)F (t(1/2)=110 min) instead of
      (11)C (t(1/2)=20 min), [(18)F]fluoroethylcholine has been introduced to increase
      the opportunity of widespread clinical application. Nevertheless, the various
      known synthetic methods provide [(18)F]fluoroethylcholine for human use only in
      moderate overall yields of up to 30% so far. Here, a new simplified and high
      yield two-step-synthesis for [(18)F]fluoroethylcholine is described for potential
      clinical applications starting from 2-bromoethyl triflate (BETfO) using a
      modified, commercially available fully automated synthesis module. All synthesis
      parameters were subsequently optimized resulting in a total yield of 47+/-5% (not
      decay corrected) in only 40min. [(18)F]fluoroethylcholine could be obtained ready
      for human use as physiological solution after fixation on Sep-Pak Accell Light
      cartridges (waters((R))) and formulation with saline without the need of GC or
      HPLC purification. Radiochemical purity was >99.9% and no contamination of the
      sterile solution with chemicals used during the synthesis was detected.

PMID- 18819810
TI  - Identification of minimal sequence for HIV-1 fusion inhibitors.
AB  - Emergence of multi-drug resistant HIV-1 is a serious problem for AIDS treatment.
      Recently, the virus-cell membrane fusion process has been identified as a
      promising target for the development of novel drugs against these resistant
      variants. In this study, we identified a 29-residue peptide fusion inhibitor,
      SC29EK, which shows activity comparable to the previously reported inhibitor
      SC35EK. Some residues in SC29EK not required for interaction with virus gp41
      heptad repeat 1 (HR1) were replaced with a non-proteinogenic amino acid, 2
      aminoisobutyric acid (Aib), to stabilize the alpha-helix structure and to provide
      resistance to peptidases.

PMID- 18819811
TI  - Carbonic anhydrase inhibitors: synthesis and inhibition studies against mammalian
      isoforms I-XV with a series of 2-(hydrazinocarbonyl)-3-substituted-phenyl-1H
      indole-5-sulfonamides.
AB  - A series of 2-(hydrazinocarbonyl)-3-substitutedphenyl-1H-indole-5-sulfonamides
      possessing various 2-, 3- or 4- substituted phenyl groups with methyl-, halogeno-
      and methoxy- functionalities, as well as the perfluorophenyl moiety have been
      synthesized and evaluated as inhibitors of 13 catalytically active, mammalian
      carbonic anhydrase (CA, EC 4.2.1.1) isoforms, that is, CA I-CA XV (of human (h)
      or murine (m) origin). The new compounds were ineffective inhibitors of isozymes
      hCA III, hCA IV, hCA VA, hCA VB, hCA VI and mCA XIII, moderate inhibitors of hCA
      I, hCA VII, hCA IX and mCA XV, and excellent, low-nanomolar inhibitors of hCA II
      and hCA XIV. The substitution pattern of the aromatic group in the 3-position of
      the indole ring influenced biological activity and isozyme inhibition profiles in
      this series of sulfonamides. Some of the best and most selective hCA XIV and mCA
      XV inhibitors ever reported have been identified in this study.

PMID- 18819812
TI  - Antioxidant capacity of human blood plasma and human urine: simultaneous
      evaluation of the ORAC index and ascorbic acid concentration employing pyrogallol
      red as probe.
AB  - The oxygen radical absorbance capacity (ORAC) methodology has been employed to
      estimate the antioxidant capacity of human blood plasma and human urine using
      pyrogallol red (ORAC-PGR) as target molecule. Uric acid, reduced glutathione,
      human serum albumin, and ascorbic acid (ASC) inhibited the consumption of
      pyrogallol red, but only ASC generated an induction time. Human blood plasma and
      human urine protected efficiently pyrogallol red. In these assays, both
      biological fluids generated neat induction times that were removed by ascorbate
      oxidase. From these results, ORAC-PGR method could be proposed as a simple
      alternative to evaluate an ORAC index and, simultaneously, to estimate the
      concentration of ascorbic acid in human blood plasma or human urine.

PMID- 18819813
TI  - New ferrocenic pyrrolo[1,2-a]quinoxaline derivatives: synthesis, and in vitro
      antimalarial activity.
AB  - Following our search for antimalarial compounds, novel series of ferrocenic
      pyrrolo[1,2-a]quinoxaline derivatives 1-2 were synthesized from various
      substituted nitroanilines and tested for in vitro activity upon the erythrocytic
      development of Plasmodiumfalciparum strains with different chloroquine-resistance
      status. The pyrrolo[1,2-a]quinoxalines 1 were prepared in 6-8 steps through a
      regioselective palladium-catalyzed monoamination by coupling 4-chloropyrrolo[1,2
      a]quinoxalines with 1,3-bis(aminopropyl)piperazine or -methylamine using Xantphos
      as the ligand. The ferrocenic bispyrrolo[1,2-a]quinoxalines 2 were prepared by
      reductive amination of previously described bispyrrolo[1,2-a]quinoxalines 9 with
      ferrocene-carboxaldehyde, by treatment with NaHB(OAc)(3). The best results were
      observed with ferrocenic pyrrolo[1,2-a]quinoxalines linked by a bis(3
      aminopropyl)piperazine. Moreover, it was observed that a methoxy group on the
      pyrrolo[1,2-a]quinoxaline nucleus and no substitution on the terminal N
      ferrocenylmethylamine function enhanced the pharmacological activity. Selected
      compounds 1b, 1f-h, 1l and 2a were tested for their ability to inhibit beta
      haematin formation, the synthetic equivalent of hemozoin, by using the HPIA (heme
      polymerization inhibitory activity) assay. Of the tested compounds, only 2a
      showed a beta-haematin formation inhibition, but no inhibition of haem
      polymerization was observed with the other selected ferrocenic monopyrrolo[1,2
      a]quinoxaline derivatives 1b, 1f-h and 1l, as the IC(50) values were superior to
      10 equivalents.

PMID- 18819815
TI  - Antitumor studies. Part 5: Synthesis, antitumor activity, and molecular docking
      study of 5-(monosubstituted amino)-2-deoxo-2-phenyl-5-deazaflavins.
AB  - Various novel 5-(monosubstituted amino)-2-deoxo-2-phenyl-5-deazaflavins
      derivatives have been synthesized by direct coupling of 5-deazaflavins and N
      alkyl or aryl amines. The antitumor activities against human tumor cell lines
      CCRF-HSB-2 and KB cells have been investigated in vitro and many compounds showed
      promising potential antitumor activities with less cytotoxicities. AutoDock
      molecular docking into PTK (PDB code: 1t46) has been done for lead optimization
      of these compounds as potential PTK inhibitors. Some of the synthesized 5
      (monosubstituted amino)-2-deoxo-2-phenyl-5-deazaflavins at the 5-position
      exhibited reasonable binding affinities into PTK with the hydrogen bond through
      their C(5)-NH moiety.

PMID- 18819814
TI  - Sequence specific and high affinity recognition of 5'-ACGCGT-3' by rationally
      designed pyrrole-imidazole H-pin polyamides: thermodynamic and structural
      studies.
AB  - Imidazole (Im) and Pyrrole (Py)-containing polyamides that can form stacked
      dimers can be programmed to target specific sequences in the minor groove of DNA
      and control gene expression. Even though various designs of polyamides have been
      thoroughly investigated for DNA sequence recognition, the use of H-pin polyamides
      (covalently cross-linked polyamides) has not received as much attention.
      Therefore, experiments were designed to systematically investigate the DNA
      recognition properties of two symmetrical H-pin polyamides composed of PyImPyIm
      (5) or f-ImPyIm (3e, f=formamido) tethered with an ethylene glycol linker. These
      compounds were created to recognize the cognate 5'-ACGCGT-3' through an
      overlapped and staggered binding motif, respectively. Results from DNaseI
      footprinting, thermal denaturation, circular dichroism, surface plasmon resonance
      and isothermal titration microcalorimetry studies demonstrated that both H-pin
      polyamides bound with higher affinity than their respective monomers. The binding
      affinity of formamido-containing H-pin 3e was more than a hundred times greater
      than that for the tetraamide H-pin 5, demonstrating the importance of having a
      formamido group and the staggered motif in enhancing affinity. However, compared
      to H-pin 3e, tetraamide H-pin 5 demonstrated superior binding preference for the
      cognate sequence over its non-cognates, ACCGGT and AAATTT. Data from SPR
      experiments yielded binding constants of 1.6x10(8)M(-1) and 2.0x10(10)M(-1) for
      PyImPyIm H-pin 5 and f-ImPyIm H-pin 3e, respectively. Both H-pins bound with
      significantly higher affinity (ca. 100-fold) than their corresponding unlinked
      PyImPyIm 4 and f-ImPyIm 2 counterparts. ITC analyses revealed modest enthalpies
      of reactions at 298 K (DeltaH of -3.3 and -1.0 kcal mol(-1) for 5 and 3e,
      respectively), indicating these were entropic-driven interactions. The heat
      capacities (DeltaC(p)) were determined to be -116 and -499 cal mol(-1)K(-1),
      respectively. These results are in general agreement with DeltaC(p) values
      determined from changes in the solvent accessible surface areas using complexes
      of the H-pins bound to (5'-CCACGCGTGG)(2). According to the models, the H-pins
      fit snugly in the minor groove and the linker comfortably holds both polyamide
      portions in place, with the oxygen atoms pointing into the solvent. In summary,
      the H-pin polyamide provides an important molecular design motif for the
      discovery of future generations of programmable small molecules capable of
      binding to target DNA sequences with high affinity and selectivity.

PMID- 18819816
TI  - Perylene side chains modulate G-quadruplex conformation in biologically relevant
      DNA sequences.
AB  - The stabilisation of different G-quadruplex intra- and intermolecular structures
      by a number of perylene derivatives characterised by side chains ending with
      linear or cyclic amines was investigated by electrophoretic (EMSA) and
      spectroscopic (CD) techniques. The G-rich sequences included the biologically
      relevant human telomeric TTAGGG runs and the NHE region of the c-myc oncogene.
      The test compounds could be subdivided into two families: derivatives carrying a
      cyclic amine in the side chains, which show a reduced binding to the G-quadruplex
      form, and linear amine congeners, exhibiting enhanced affinity. The latter
      efficiently induce pairing of multiple DNA chains, while the former are not able
      to overcome the original folding of the nucleic acid sequence which is preserved
      in the complex. Remarkably, addition of the perylenes to G-rich sequences paired
      in a double helical form results in G-quadruplex induction by weak binders only.
      This is likely related to the ability of strong G-quadruplex binders, but not of
      weak G-quadruplex binders, to efficiently intercalate into the double-stranded
      arrangement, which becomes stabilised and is not prone to undergo denaturation
      and subsequent G-quadruplex folding essentially for kinetic reasons. Hence, two
      apparently conflicting requirements emerge from this work. In fact, linear
      alkylamino terminals in the perylene side chains are capable of strong and
      selective G-quadruplex recognition, but only cyclic amine end groups favour
      duplex-quadruplex transitions that are likely crucial to produce biological and
      pharmacological effects in living systems.

PMID- 18819817
TI  - Parallel factor analysis of spider fluorophores.
AB  - Fluorophores from the hemolymph of yellow sac spiders (Cheiracanthium mildei)
      have been characterized using excitation emission matrix (EEM) fluorescence
      spectroscopy. This approach provides characterization of fluorophores present in
      the organism without having to isolate pure samples. Minimal variation occurs
      between individual samples and each EEM has two distinct peaks, suggesting two
      fluorophores may be present in the hemolymph. Parallel factor analysis reveals
      that three fluorophores (with excitation and emission maxima at 270/319, 330/389,
      and 350/465 nm) best explains the sample to sample variation. By comparing the
      spectra of the three individual components to fluorophores found in scorpions it
      is shown that these spiders possess different fluorophores than scorpions.
      Furthermore, the fluorescence observed is not consistent with beta-carboline or 4
      methyl-7-hydroxycoumarin, two compounds previously described in scorpions.

PMID- 18819818
TI  - The genetics of cardiovascular disease.
AB  - Recent advances in genotyping technology and insights into disease mechanisms
      have increased interest in the genetics of cardiovascular disease. Several
      candidate genes involved in cardiovascular diseases were identified from studies
      using animal models, and the translation of these findings to human disease is an
      exciting challenge. There is a trend towards large-scale genome-wide association
      studies that are subject to strict quality criteria with regard to both
      genotyping and phenotyping. Here, we review some of the strategies that have been
      developed to translate findings from experimental models to human disease and
      outline the need for optimizing global approaches to analyze such results.
      Findings from ongoing studies are interpreted in the context of disease pathways
      instead of the more traditional focus on single genetic variants.

PMID- 18819819
TI  - IL-18 is correlated with type-2 immune response in children with steroid
      sensitive nephrotic syndrome.
AB  - Children with steroid sensitive nephrotic syndrome (SSNS) is thought to have
      dysregulated type-1/type-2 cytokine network. Interleukin (IL)-18 is a cytokine,
      which may enhance both type-1 and type-2 responses, depending on the cytokines
      milieu. This prospective study aimed to assess type-1/type-2 cytokine synthesis
      and production profile in different stages of SSNS and define the potent
      involvement of IL-18. Twenty-three children with SSNS, aged 2.5-14 years, were
      studied; 23/23 both in active stage before treatment initiation and in remission
      still on steroids; 15/23 in remission off steroids as well. Data were compared
      with those obtained from 25 age-matched controls. The following parameters were
      assessed: Basic T cell populations, percentages of CD3+/CD69+/IFN-gamma+ and
      CD3+/CD69+/IL-4+ T cells as well as serum levels of IFN-gamma, IL-2, IL-4, IL-13
      and IL-18. No difference in IL-2 levels was found between nephrotic children of
      all disease stages and controls (p>0.05). Percentage of CD3+/CD69+/IL-4+ T cells
      and serum levels of IL-4, IL-13 and IL-18 were significantly higher in the active
      stage of SSNS compared with the remission stages and controls (p<0.05). On the
      contrary, percentage of CD3+/CD69+/IFN-gamma+ T cells as well as serum IFN-gamma
      were significantly lower during active disease stage compared with remission
      stages and controls (p<0.05). In children with SSNS, of all disease stages, serum
      levels of IL-18 were significantly correlated with both IL-4 and IL-13 (r=0.628
      and p<0.0001, r=0.71 and p<0.0001, respectively). It seems that a type-2 cytokine
      synthesis and production pattern prevails in children with active SSNS and IL-18
      expression is significantly correlated with this type-2 immune response.

PMID- 18819820
TI  - Augmentation of antibody responses by retinoic acid and costimulatory molecules.
AB  - Antibody production is crucial for a successful vaccine response. Beyond the
      ability of vitamin A (VA) and its active metabolite, all-trans-retinoic acid (RA)
      to restore growth in VA-deficient animals, supplementation with VA and/or
      treatment with RA can augment antibody responses in both VA-deficient and VA
      adequate animals. RA alone, and in combination with stimuli that are ligands for
      the Toll-like receptor family, can augment the adaptive immune response leading
      to a heightened primary antibody response, and a stronger recall response upon
      restimulation. Mechanisms may include regulation of cell populations, type 1/type
      2 cytokines, and B cell-related transcription factors, leading to accelerated B
      cell maturation.

PMID- 18819821
TI  - High frequency vibration conditioning stimulation centrally reduces myoelectrical
      manifestation of fatigue in healthy subjects.
AB  - OBJECTIVE: Vibration conditioning has been adopted as a tool to improve muscle
      force and reduce fatigue onset in various rehabilitation settings. This study was
      designed to asses if high frequency vibration can induce some conditioning
      effects detectable in surface EMG (sEMG) signal; and whether these effects are
      central or peripheral in origin. DESIGN: 300 Hz vibration was applied for 30 min
      during 5 consecutive days, to the right biceps brachii muscle of 10 healthy males
      aged from 25 to 50 years. sEMG was recorded with a 16 electrode linear array
      placed on the skin overlying the vibrated muscle. The test protocol consisted of
      30% and 60% maximal voluntary contraction (MVC) as well as involuntary
      (electrically elicited) contractions before and after treatment. RESULTS: No
      statistically significant differences were found between PRE and POST vibration
      conditioning when involuntary stimulus-evoked contraction and 30% MVC were used.
      Significant differences in the initial values and rates of change of muscle fibre
      conduction velocity were found only at 60% MVC. CONCLUSIONS: 300 Hz vibration did
      not induce any peripheral changes as demonstrated by the lack of differences when
      fatigue was electrically induced. Differences were found only when the muscle was
      voluntarily fatigued at 60% MVC suggesting a modification in the centrally driven
      motor unit recruitment order, and interpreted as an adaptive response to the
      reiteration of the vibratory conditioning.

PMID- 18819822
TI  - Deletion of frizzled-related protein reduces voluntary running exercise
      performance in mice.
AB  - OBJECTIVE: To study the effect of frizzled-related protein (Frzb) deletion in
      mice on voluntary running wheel exercise performance and osteoarthritis. METHODS:
      At the age of 7 weeks, Frzb(-/-) and wild-type mice were grouped and a running
      wheel was introduced into the cage. At week 8, all mice were caged solitarily
      with a running wheel available. Mice were allowed free exercise for 6-12 months
      and distances run were recorded daily. Non-running mice were used as additional
      control group. X-rays of knees and hips were taken at different time points. At
      the end of the experiment, mice were sacrificed and joints were processed for
      histological evaluation. Cartilage damage, synovitis and osteophyte formation
      were scored. Muscle fiber composition of the soleus and extensor digitorum longus
      was studied by immunofluorescence. RESULTS: At the age of 6 months, both female
      and male wild-type mice showed a significantly greater exercise performance than
      the Frzb(-/-) mice (P<0.05). At 1 year, the difference was still significant for
      male mice, but not for females. Running exercise did not significantly affect
      severity of osteoarthritis. No statistical differences in osteoarthritis severity
      were seen between Frzb(-/-) mice and wild-type mice. No differences were seen in
      muscle composition between Frzb(-/-) mice and wild-type mice. CONCLUSION: Absence
      of Frzb in mice reduced voluntary exercise performance in running wheels. These
      experiments demonstrate that the effects of genes in mice can also be evaluated
      using functional outcomes such as running wheel exercise performance, similar to
      evolving practice in human clinical trials.

PMID- 18819823
TI  - Outcomes of endovascular repair of acute thoracic aortic injury: interrogation of
      the New Zealand thoracic aortic stent database.

PMID- 18819824
TI  - Hypocretin/orexin disturbances in neurological disorders.
AB  - The hypothalamic hypocretin (orexin) system plays a crucial role in the
      regulation of sleep and wakefulness. The strongest evidence for this is the fact
      that the primary sleep disorder narcolepsy is caused by disrupted hypocretin
      signaling in humans as well as various animal models. There is a growing interest
      in the role of hypocretin defects not only in the pathophysiology of other sleep
      disorders, but also in neurological diseases with associated sleep
      symptomatology. In this paper we first review the current methods to measure the
      integrity of the hypocretin system in human patients. The most widely used
      technique entails the measurement of hypocretin-1 in lumbar cerebrospinal fluid.
      In addition, hypocretin levels can be measured in ventricular cerebrospinal fluid
      and brain tissue extract. Finally, in post-mortem hypothalamic material, the
      number of hypocretin neurons can be precisely quantified. In the second part of
      this paper we describe the various neurological disorders in which hypocretin
      defects have been reported. These include neurodegenerative, neuromuscular and
      immune-mediated diseases, as well as traumatic brain injury. We conclude with a
      discussion of the functional relevance of partial hypocretin defects, and the
      various pathophysiological mechanisms that can lead to such defects.

PMID- 18819825
TI  - A review of nighttime eating disorders.
AB  - Nighttime eating is categorized as either night eating syndrome (NES) or sleep
      related eating disorder (SRED). These conditions represent an interruption in the
      overnight fast that characterizes human sleep. A critical review of the
      literature on NES and SRED will suggest that they are situated at opposite poles
      of a disordered eating spectrum. NES could be considered an abnormality in the
      circadian rhythm of meal timing with a normal circadian timing of sleep onset.
      Conversely, the feeding behavior in SRED is characterized by recurrent episodes
      of eating after an arousal from nighttime sleep with or without amnesia. Both
      conditions are often relentless and chronic. Multiple definitions of night eating
      have limited our ability to determine the exact prevalence of NES. Studies have
      suggested that central nervous system (CNS) serotonin modulation may lead to an
      effective treatment of NES. SRED is frequently associated with other sleep
      disorders, in particular parasomnias. Early studies have shown that the anti
      seizure medication topiramate may be an effective treatment for SRED.

PMID- 18819826
TI  - Band selective small flip angle COSY: a simple experiment for the analyses of 1H
      NMR spectra of small chiral molecules.
AB  - The NMR spectroscopic discrimination of enantiomers in the chiral liquid
      crystalline solvent is more often carried out using (2)H detection in its natural
      abundance. The employment of (1)H detection for such a purpose is severely
      hampered due to significant loss of resolution in addition to indistinguishable
      overlap of the spectra from the two enantiomers. This study demonstrates that the
      band selected small flip angle homonuclear correlation experiment is a simple and
      robust technique that provides unambiguous discrimination, very high spectral
      resolution, reduced multiplicity of transitions, relative signs of the couplings
      and enormous saving of instrument time.

PMID- 18819827
TI  - Quasioptical study of antiferromagnetic resonance in YFeO3 at submillimeter
      wavelength under high pulsed magnetic fields.
AB  - Transmission spectra, T(H), of linearly polarized electromagnetic waves through
      YFeO(3), weak ferromagnet, measured at frequencies nu=96-1000 GHz in long-pulsed
      magnetic fields (H||k||c-axis, Faraday geometry) exhibit strong rotation of the
      polarization plane near the quasiferromagnetic AFMR as well as low frequency
      impurity modes. New ascending impurity branch including five lines was observed
      at high magnetic field (10-30 T) at 96 GHz and 140 GHz in addition to the known
      low-field descending impurity branch. Behavior of all the impurity modes assigned
      to transitions in (6)S(5/2) multiplet of Fe(3+) "impurity" ions in c-sites was
      described self-consistently by one spin-Hamiltonian. A theoretical calculation of
      dynamical magnetic susceptibility at AFMR and impurity modes and further
      simulation of transmission spectra made it possible to describe the main features
      of the observed spectra T(H). It was found that the T(H) behavior is determined
      at resonances not only by non-diagonal components of the magnetic susceptibility
      but also by the anisotropy of the dielectric permittivity (epsilon(xx)(') not
      equal epsilon(yy)(')), i.e. birefringence.

PMID- 18819828
TI  - The long posterior sacroiliac ligament: a histological study of morphological
      relations in the posterior sacroiliac region.
AB  - OBJECTIVES: To investigate the morphology of the long posterior sacroiliac
      ligament (LPSL) and its potential relationship to adjacent structures in the
      posterior sacroiliac region, and to consider any possible functional anatomical
      implications that may arise. METHODS: Four large cadaveric tissue blocks of the
      posterior sacroiliac region were utilised in this qualitative histological study.
      The blocks underwent demineralisation in ethyl-diamine-tetra-acetic acid (EDTA).
      The end-point was determined radiographically. The demineralised tissue blocks
      were subsequently processed and a base sledge microtome used to section the
      blocks. Sequential sections were stained with Harris haematoxylin and alcoholic
      eosin (H&E) and mounted on glass slides prior to viewing under a light
      microscope. RESULTS: The LPSL was observed to have proximal and distal regions of
      osseous attachment. Between these regions of attachment the middle LPSL was
      observed as a confluence of three layers: the erectores spinae aponeurosis, the
      'deep fascial layer' and the gluteal aponeurosis. Deep to the 'deep fascial
      layer' a layer of adipose and loose connective tissue was observed. Lateral
      branches of the dorsal sacral rami were identified within this layer.
      CONCLUSIONS: The middle long posterior ligament appears to provide a pathway for
      the lateral branches of the dorsal sacral rami between the posterior sacral
      region and the gluteal region. This histological study provides a morphological
      basis for the proposal that putative sacroiliac joint pain may be due to an
      entrapment neuropathy of the lateral branches of the dorsal sacral rami at the
      long posterior sacroiliac ligament.

PMID- 18819829
TI  - Psoas impingement syndrome in hip osteoarthritis.
AB  - The degenerative processes underlying osteoarthritis of the hip produce both
      anatomical and biomechanical changes in and around the involved joint. A good
      understanding of hip anatomy and the forces crossing the hip joint is essential
      to understand both hip pathology and current treatment techniques. Total hip
      arthroplasty (THA) has become a mainstay of treatment for advanced osteoarthritis
      of the hip. Several factors contribute to post-operative hip pain in THA
      patients. Iliopsoas impingement on the prosthetic cup after total hip replacement
      is one of the causes of pain following hip surgery, often due to an anterior
      overlap of the implant with respect to the acetabulum. The anatomic shape of the
      anterior acetabular ridge, which may be straight or curved, influences this
      overlap. In this paper we present a case illustrating a psoas impingement-like
      syndrome in a patient with severe hip osteoarthritis who has not undergone hip
      replacement surgery. We discuss the compensatory strategies employed by the
      patient to reduce pain and prevent falls, and show CT scan images depicting the
      underlying anatomic pathology.

PMID- 18819830
TI  - Cervico-thoracic juxtafacet cyst causing spinal foraminal widening.

PMID- 18819831
TI  - Fibromyalgia syndrome in the general population of France: a prevalence study.
AB  - OBJECTIVE: To estimate the prevalence of fibromyalgia (FM) syndrome in the French
      general population. METHODS: A validated French version of the London
      Fibromyalgia Epidemiology Study Screening Questionnaire (LFESSQ) was administered
      via telephone to a representative community sample of 1014 subjects aged over 15
      years, selected by the quota method. A positive screen was defined as: (1)
      meeting the 4-pain criteria alone (LFESSQ-4), or (2) meeting both the 4-pain and
      2-fatigue criteria (LFESSQ-6). To estimate the positive predictive value of
      LFESSQ-4 and LFESSQ-6, this questionnaire was submitted to a sample of
      rheumatology outpatients (n=178), who were then examined by a trained
      rheumatologist to confirm or exclude the diagnosis of FM according to the 1990
      American College of Rheumatology criteria. The prevalence of FM in the general
      population was estimated by applying the predictive positive value to eligible
      community subjects (i.e., positive screens). RESULTS: In the community sample,
      9.8% and 5.0% screened positive for LFESSQ-4 and LFESSQ-6, respectively. Among
      rheumatology outpatients, 47.1% screened positive for LFESSQ-4 and 34.8% for
      LFESSQ-6 whereas 10.6% were confirmed FM cases. Based on positive screens for
      LFESSQ-4, the prevalence of FM was estimated at 2.2% (95% CI 1.3-3.1) in the
      French general population. The corresponding figure was 1.4 % (95% CI 0.7-2.1) if
      positive screens for LFESSQ-6 were considered. CONCLUSION: Our findings suggest
      that FM is also a major cause of widespread pain in France since a point
      prevalence of 1.4% would translate in approximately 680,000 patients.

PMID- 18819832
TI  - Osteolysis syndrome mimicking juvenile idiopathic arthritis.
AB  - Osteolysis syndromes include a group of heterogeneous disorders that can be
      mistakenly diagnosed as juvenile idiopathic arthritis (JIA) in early course of
      the disease. We report a case of 16-year-old girl who presented with severe joint
      deformities, subcutaneous nodules and linear skin indurations. She had been
      diagnosed as having JIA before and given immunosuppressive therapy. X-ray of the
      joints showed severe osteopenia and osteolysis of interphalangeal joints of the
      hands and feet. The patient was diagnosed as having Torg/nodulosis, arthropathy,
      osteolysis syndrome (NAO). Here, we briefly discuss osteolysis syndromes and the
      differential diagnosis between osteolysis syndromes and JIA.

PMID- 18819833
TI  - Acute tenosynovitis of the ankle due to Capnocytophaga cynodegmi/canimorsus as
      identified by 16S rRNA gene sequencing.

PMID- 18819834
TI  - [Systematic labor induction at 41(+0) weeks of gestation: pros and cons].

PMID- 18819835
TI  - Robust 3D reconstruction and identification of dendritic spines from optical
      microscopy imaging.
AB  - In neurobiology, the 3D reconstruction of neurons followed by the identification
      of dendritic spines is essential for studying neuronal morphology, function and
      biophysical properties. Most existing methods suffer from problems of low
      reliability, poor accuracy and require much user interaction. In this paper, we
      present a method to reconstruct dendrites using a surface representation of the
      neuron. The skeleton of the dendrite is extracted by a procedure based on the
      medial geodesic function that is robust and topology preserving, and it is used
      to accurately identify spines. The sensitivity of the algorithm on the various
      parameters is explored in detail and the method is shown to be robust.

PMID- 18819836
TI  - Comparing the application of Health Information Technology in primary care in
      Denmark and Andalucia, Spain.
AB  - BACKGROUND: It is generally acknowledged that Denmark is one, if not the, leading
      country in terms of the use of information technology by its primary care
      physicians. Other countries, notably excluding the United States and Canada, are
      also advanced in terms of electronic medical records in general practitioner
      offices and clinics. PURPOSE: This paper compares the status of primary care
      physician office computing in Andalucia to that of Denmark by contrasting the
      functionality of electronic medical records (EMRs) and the ability to
      electronically communicate clinical information in both jurisdictions. METHODS: A
      novel scoring system has been developed based on data gathered from databases
      held by the respective jurisdictional programs, and interviews with individuals
      involved in the deployment of the systems. The scoring methodology was applied
      for the first time in a comparison of the degree of automation in primary care
      physician offices in Denmark and the province of Alberta in Canada. It was also
      used to compare Denmark and New Zealand. This paper is the third offering of this
      method of scoring the adoption of electronic medical records in primary care
      office settings which hopefully may be applicable to other health jurisdictions
      at national, state, or provincial levels. RESULTS: Although similar in many
      respects, there are significant differences between these two relatively
      autonomous health systems which have led to the rates of uptake of physician
      office computing. Particularly notable is the reality that the Danish primary
      care physicians have individual "Electronic Medical Records" while in Andalucia,
      the primary care physicians share a common record which when secondary care is
      fully implemented will indeed be an "Electronic Health Record". CONCLUSION: It is
      clear that the diffusion of technology, within the primary care physician sector
      of the health care market, is subject to historical, financial, legal, cultural,
      and social factors. This tale of two places illustrates the issues, and different
      ways that they have been addressed.

PMID- 18819837
TI  - Polyomaviruses BK- And JC-DNA quantitation in kidney allograft biopsies.
AB  - BACKGROUND: Polyomavirus-associated nephropathy (PVAN) is one of the most common
      viral disease affecting renal allograft, with BK being the most frequent causal
      agent and JCV being considered responsible in <3% of the cases. OBJECTIVES: To
      quantify polyomaviruses BK and JC load by real-time TaqMan PCR in tissue
      specimens (renal and ureteral) from kidney transplant recipients. STUDY DESIGN
      AND METHODS: One-hundred-thirty-eight specimens (125 kidneys, 13 ureters)
      obtained from 109 patients were evaluated by quantitative real-time PCR for the
      detection of BKV- and JCV-DNA. Demographic, virological, and histopathological
      data were collected. RESULTS: BKV-DNA was positive in 32 of 109 patients (29.6%)
      and JCV-DNA in 20 of 109 patients (18.3%). The highest BK viral loads (>10(4)
      genome equivalents/cell) were found in two renal samples with histopathologically
      confirmed PVAN; while JC viral load was >10(4) genome equivalents/cell in one
      ureteral sample. CONCLUSIONS: Although quantitation of viral DNA on renal
      allograft biopsies could be complementary to histopathological evaluation and the
      highest viral load are detectable in renal specimens with PVAN, the
      identification of a diagnostic cut-off should require further studies.

PMID- 18819838
TI  - Comparison of two highly automated DNA extraction systems for quantifying Epstein
      Barr virus in whole blood.
AB  - BACKGROUND: Optimal automated molecular methods are needed to monitor Epstein
      Barr virus (EBV) infections in transplant recipients. OBJECTIVES: To compare the
      extraction of EBV DNA from whole blood using the COBAS Ampliprep and the MagNA
      Pure instruments (Roche) for quantifying EBV DNA by real-time PCR. STUDY DESIGN:
      EBV DNA content was determined on clinical samples extracted by both systems.
      RESULTS: The detection limit was 2.16log(10)copies/mL using the COBAS Ampliprep
      extraction system. Specificity was 100% and we saw no cross-contamination.
      Extraction was linear from 2.60 to 5.60log(10)copies/mL. The intra-assay
      variation was 1.91% for 3.60, 2% for 4.60 and 4.51% for 5.60log(10)copies/mL;
      inter-assay variation was 4.88%. Sixty-six samples were tested: 26 were positive
      and 28 were negative by both methods. One sample was MagNA Pure positive/COBAS
      Ampliprep negative (virus load 3.15log(10)copies/mL) and 10 samples were MagNA
      Pure negative/COBAS Ampliprep positive (virus loads from 1.59 to
      3.51log(10)copies/mL) (P<0.0001). Both methods gave similar quantitative results
      (average difference 0.07log(10)copies/mL) which were well correlated (r=0.73,
      P<0.001). CONCLUSIONS: The COBAS Ampliprep extraction system is comparable to the
      MagNA Pure and offers a high reliability for extracting EBV DNA from whole blood.

PMID- 18819839
TI  - Reactivation of Polyomavirus hominis 1 (BKV) during pregnancy and the risk of
      mother-to-child transmission.
AB  - BACKGROUND: Pregnancy is associated with down-regulation of immune responses of
      the mother. This might lead to reactivation and vertical transmission of latent
      viral infections such as BK virus (BKV). OBJECTIVES: To determine the presence of
      BKV in the urine of pregnant women and in cord blood at delivery. STUDY DESIGN:
      We examined urines from 52 pregnant women and 51 cord blood samples for BKV by
      real-time SYBR green PCR. RESULTS: BKV DNA was found in the urine of 18 (34.6%)
      pregnant women. No BKV DNA was detected by SYBR green PCR in the cord blood
      specimens. CONCLUSIONS: BKV reactivation is common during pregnancy but this is
      not associated with BKV in cord blood.

PMID- 18819840
TI  - Nursing students' self-perceptions as insiders in the practice culture.
AB  - Nursing students must be able to function comfortably, confidently, and
      competently within the culture of nursing when they graduate. Although different
      models of clinical teaching are used to acculturate undergraduate nursing
      students to their professional practice roles, it is not known to what extent
      acculturation is affected by these models. The two-fold purpose of this study was
      to compare self-perceptions as insiders of students involved in preceptored and
      instructor led clinical experiences and to identify factors contributing to
      students self-perceptions as insiders. Using a non-equivalent group's prepost-
      test design, 38 undergraduate students, participated either in traditional
      instructor led practicums or summer externships. In addition to a background
      questionnaire, students completed an investigator generated perceptions of self
      in the clinical practice culture scale prior to, and at the end of, their
      clinical experiences. Findings revealed that both groups of students demonstrated
      significant changes in their self-perceptions as insiders as a result of their
      clinical experiences but there was no significant interaction effect of clinical
      teaching model and time on students' insider self-perceptions. Students
      identified multiple factors that influenced their insider perceptions.
      Implications of these finding are discussed.

PMID- 18819841
TI  - The critical practice of professing nursing: a contribution to the professors of
      nursing debate.

PMID- 18819843
TI  - Idiopathic neutropenia of childhood is associated with Fas/FasL expression.
AB  - Idiopathic neutropenia (IN) in children is characterized by decreased neutrophil
      counts (<1500/microl), can be acute or chronic (greater than 6 months duration).
      The pathophysiology is not well understood; therefore, potential mechanisms of
      pediatric IN were investigated. An increase in Fas transcripts in neutrophils of
      IN patients compared to age-matched healthy control (HC) neutrophils was observed
      (p<0.005). Increased expression of Fas protein was found in IN neutrophils, while
      Fas surface expression on other immune cells was similar. Plasma from acute IN
      patients had higher protein levels of soluble FasL than chronic IN patients. When
      HC neutrophils were incubated in plasma from IN patients, greater rates of
      apoptosis were observed. Biochemical studies suggest the apoptotic factor(s) in
      plasma is heat-sensitive, non-IgG, and 12-50 kD protein. Addition of anti-sFasL
      blocking antibodies to patient plasma caused a statistically significant decrease
      in neutrophil apoptosis. These studies show that the Fas/FasL pathway could be
      associated with neutrophil apoptosis in childhood IN.

PMID- 18819842
TI  - NLRC4/IPAF: a CARD carrying member of the NLR family.
AB  - The NOD-like receptor (NLR) family of proteins is involved in the regulation of
      innate immune responses and cell death pathways. Recent findings show that the
      NLR family member NLRC4 (also known as IPAF) has important roles in innate immune
      responses to Gram-negative bacteria. Macrophages infected with Legionella
      pneumophila, Salmonella typhimurium, Shigella flexneri, or Pseudomonas aeruginosa
      activate caspase-1 in an NLRC4-dependent manner leading to macrophage cell death
      and the release of proinflammatory cytokines. This review will discuss these
      findings as well as the role of bacterial type III and type IV secretion systems
      and flagellin in NLRC4-mediated caspase-1 activation.

PMID- 18819844
TI  - Introduction to immunoregulation in chronic inflammatory disorders.

PMID- 18819845
TI  - Ethylenecarbodiimide-coupled allogeneic antigen presenting cells induce human
      CD4+ regulatory T cells.
AB  - Adoptive transfer of naturally occurring CD4(+)CD25(+) regulatory T cells can
      tolerize transplantation alloresponses in animal models. However isolation of
      these cells in sufficient numbers from humans is cumbersome and prone to
      contamination with alloreactive CD25(+) T cells. Incubation of
      ethylenecarbodiimide-coupled antigen presenting cells (APC) with naive T cells
      and antigen has been shown to induce tolerance in various experimental models. We
      therefore investigated whether ECDI-coupled allogeneic APC were able to induce an
      expandable human CD4(+) Treg population. CD4(+) and CD4(+) CD25(-) cells cultured
      for 5 days with ECDI-treated human PBMC exhibited potent suppressive capacity in
      a mixed lymphocyte reaction. Induction of these ECDI-Tregs was associated with up
      regulation of Foxp3 mRNA and protein expression and they maintained high
      expression of CD62L and CD27 as well as low CD127 expression. ECDI-treated APC
      displayed reduced expression of the co-stimulatory signaling molecules CD40 and
      CD80, and failed to stimulate proliferation and cytokine secretion in co-cultured
      CD4(+) T cells. Restimulation in the presence of rapamycin and hrIL-2 led to
      expansion of ECDI-Tregs with increasing Foxp3 levels and suppressive activity
      significantly higher than expanded naturally occurring CD4(+)CD25(+) Tregs. In
      summary these findings support the hypothesis that ECDI-coupled APC can convert
      naive CD4(+) T cells into functional Tregs with different phenotypic
      characteristics than naturally occurring CD4(+)CD25(+) Tregs. These inducible
      Tregs could provide a novel approach that might facilitate the translation of ex
      vivo generated and expanded Tregs into clinical settings.

PMID- 18819846
TI  - Risk management and medicolegal issues related to postpartum haemorrhage.
AB  - Postpartum haemorrhage (PPH) is a major cause of maternal mortality and
      morbidity. Despite several local and national guidelines and recommendations, the
      incidence of major obstetric haemorrhage has not declined significantly over the
      years. A high proportion of these cases involve patient safety incidents. The
      major themes in such incidents are: delay in diagnosis, failure to adhere to
      protocols, lack of consultant supervision, communication and documentation
      problems, inefficient teamwork and organizational failure. This chapter deals
      with ways of identifying the major contributory factors for adverse events
      associated with PPH and suggests solutions to minimize errors.

PMID- 18819847
TI  - Postpartum haemorrhage. Preface.

PMID- 18819848
TI  - Epidemiology of postpartum haemorrhage: a systematic review.
AB  - Postpartum haemorrhage (PPH) is an important cause of maternal mortality. We
      conducted a systematic review of the prevalence of PPH with the objective of
      evaluating its magnitude both globally and in different regions and settings:
      global figures, as well as regional, country and provincial variations, are
      likely to exist but are currently unknown. We used prespecified criteria to
      select databases, recorded the database characteristics and assessed their
      methodological quality. After establishing PPH (>or=500 mL blood loss) and severe
      PPH (SSPH) (>or=1000 mL blood loss) as main outcomes, we found 120 datasets
      (involving a total of 3,815,034 women) that reported PPH and 70 datasets (505,379
      women) that reported SPPH in the primary analysis. The prevalence of PPH and SPPH
      is approximately 6% and 1.86% of all deliveries, respectively, with a wide
      variation across regions of the world. The figures we obtained give a rough
      estimate of the prevalence of PPH and suggest the existence of some variations.
      For a reliable picture of PPH worldwide - its magnitude, distribution and
      consequences - a global survey tackling this condition is necessary.

PMID- 18819849
TI  - Mechanism and treatment of arrhythmias in the single ventricle patient: focus on
      intraatrial reentry.

PMID- 18819850
TI  - Exercise induced tachycardia with atrioventricular dissociation: what is the
      mechanism?

PMID- 18819851
TI  - Serendipitous discovery of a pH-dependant atropisomer bond rotation: toward a
      write-protectable chiral molecular switch?
AB  - Owing to slow rotation of a sterically constrained dimethylamide substituent, two
      slowly interconverting enantiomers of a preclinical candidate for pharmaceutical
      development, 1, (6-(3-Chloro-4-fluoro-benzyl)-4-hydroxy-2-methyl-3,5-dioxo
      2,3,5,6,7,8-hexahydro-[2,6]naphthyridine-1-carboxylic acid dimethylamide) are
      observed by chiral chromatography. Isolation of pure enantiomer by preparative
      chiral chromatography followed by enantiopurity analysis over time allowed for a
      study of the kinetics of enantiomer interconversion under a variety of
      conditions. Relatively slow racemization was observed in alcohol solvents, with a
      half life on the order of 5-10 h. A dramatic influence of aqueous buffer pH on
      racemization was noted, with higher pH leading to rapid racemization within a few
      minutes, and lower pH leading to essentially no racemization for periods up to a
      week. A hypothesis explaining this unusual effect of pH on carboxamide bond
      rotation is offered, and some suggestions for potential utility of such a system
      are considered.

PMID- 18819852
TI  - Hepatitis B virus reactivation after a resolutive acute hepatitis leading to a
      diagnosis of T cell lymphoma.
AB  - A case of hepatitis B virus reactivation leading to the diagnosis of a T cell
      lymphoma is reported. A 66-year-old woman with a past history (10 years before)
      of spontaneously recovered acute hepatitis B (with disappearance of serum
      hepatitis B surface antigen and appearance of anti-HBs), has been referred for
      hepatologic consultation for acute hepatitis. The patient was found positive
      again for hepatitis B surface antigen as well HBeAg and hepatitis B virus DNA. No
      other cause of liver disease was identified and a diagnosis of spontaneous
      hepatitis B virus reactivation was made. Five months later a peripheral T cell
      lymphoma was diagnosed. This unusual case confirms that natural immunity is not
      protective against hepatitis B virus reactivation and shows that such hepatitis B
      virus reactivation may precede the usual clinical manifestations of a peripheral
      T cell lymphoma.

PMID- 18819853
TI  - Porous composite scaffolds based on gelatin and partially hydrolyzed alpha
      tricalcium phosphate.
AB  - Porous composite scaffolds of varying compositions were prepared by freeze-drying
      gelatin foams containing increasing amounts of alpha-tricalcium phosphate (alpha
      TCP), up to about 40 wt.%. Due to the presence of gelatin, a partial hydrolysis
      of alpha-TCP into octacalcium phosphate (OCP) occurs during foaming. As a
      consequence, the scaffolds contain both alpha-TCP and OCP, in relative amounts of
      about 74% and 26%, respectively, independent of the initial composition. In
      physiological conditions the inorganic component of the scaffolds undergoes a
      further hydrolysis as shown by the finding that after immersion in phosphate
      buffered saline at 37 degrees C for 1 week the scaffolds contain poorly
      crystalline hydroxyapatite together with OCP. The scaffolds display a porous
      interconnected microstructure. The mean dimensions of the pores decrease from
      about 350 to about 170 microm as the inorganic phase content increases.
      Simultaneously, the mean values of the compression strength and Young's modulus
      increase. Stabilization of the scaffolds was obtained by using a natural, non
      toxic, crosslinking agent, genipin, which significantly improves their mechanical
      properties.

PMID- 18819854
TI  - Cytotoxicity evaluation of nanocrystalline diamond coatings by fibroblast cell
      cultures.
AB  - The cytotoxicity profile of nanocrystalline diamond (NCD) coatings on a Si(3)N(4)
      ceramic was investigated. This material is envisaged to have biomedical dental
      applications such as burrs and surgical instruments. Two fibroblast cell culture
      systems were used to address the cytotoxicity of NCD-coated samples: L929 cells
      (a mouse permanent cell line) and human gingival fibroblasts. Cell behavior was
      evaluated in terms of cell adhesion, cell viability/proliferation (mitochondrial
      function, MTT assay) and the pattern of cell growth. Fibroblast cell behavior on
      standard polystyrene culture plates was used as control, as Si(3)N(4) substrates
      have previously been shown to be biocompatible. NCD coatings provided a suitable
      surface for cell attachment, spreading and proliferation. Human gingival cells
      showed a homogeneous cytoplasm spreading, a flattened elongated morphology and a
      typical parallel alignment on confluent cultures. In comparison, L929 cells
      denoted a lower cytoplasm expansion, a heterogeneous spreading but a higher
      proliferation rate. For both cells, after few days, the NCD coating was
      completely covered with continuous cell layers. As compared to standard
      polystyrene culture plates, no deleterious or cytotoxic responses were observed
      with L929 and human fibroblast cell cultures, and in both a slight enhancement in
      cell proliferation was observed. In addition, the seeded NCD film allowed
      reproduction of the typical features of the two cell culture systems tested,
      further suggesting the lack of cytotoxicity of this coating.

PMID- 18819855
TI  - Albendazole as an adjuvant to the standard surgical management of hydatid cyst
      liver.
AB  - BACKGROUND: The treatment options for hydatid cyst liver include non-operative
      and operative methods. Operative methods include conservative and radical
      procedures. Non-operative methods include chemotherapy and percutaneous treatment
      of liver hydatidosis. MATERIAL AND METHODS: The study was conducted at Sher-i
      Kashmir Institute of Medical Sciences, Soura, Srinagar, Kashmir, India, over a
      period of two years from March 2001 to February 2003 with further follow-up of 5
      6 years. The study included 64 cases in the age group of 15 years to 64 years,
      comprising 36 males and 28 females. The aim of the study was to know the effect
      of preoperative and postoperative albendazole therapy on the viability of
      protoscolices and recurrence rate of hydatid disease of liver. Patients were
      divided into four group of 16 each. In group A, patients were directly subjected
      to surgery. In group B, patients were given albendazole for 8 weeks followed by
      surgery. In group C, patients were given albendazole for 8 weeks preoperatively
      followed by further postoperative course for 8 weeks. In group D, patients were
      first taken for surgery followed by postoperative course of albendazole for 8
      weeks. RESULTS: Out of those patients who received preoperative albendazole only
      9.37% had viable cysts at the time of surgery as compared to 96.87% of patients
      who did not receive any preoperative albendazole. In those patients who did not
      receive any albendazole therapy, recurrence rate was 18.75% whereas recurrence
      was 4.16% in patients who received albendazole therapy. CONCLUSION: We conclude
      that albendazole is safe and effective adjuvant therapy in the treatment of
      hydatid liver disease.

PMID- 18819856
TI  - Cavi-care dressings following syndactyly correction.

PMID- 18819857
TI  - Exposure of the IMA made easy.

PMID- 18819858
TI  - [Establishment of a nude mouse model of nasopharyngeal carcinoma lymph node
      metastasis and screening of the metastasis-related signature genes].
AB  - OBJECTIVE: To establish a nude mouse model of nasopharyngeal carcinoma (NPC)
      lymph node metastasis and screen the signature genes associated with the
      metastasis. METHODS: The NPC 5-8F-EGFP cells were inoculated into nude mice, from
      which a 5-8F-LN cell line with lymph node metastasis potential was obtained. The
      lymphatic metastasis-related signature genes of breast cancer and head and neck
      squamous cell carcinoma were screened by data mining method. RESULTS: The NPC
      cell lines 5-8F and 6-10B showed 307 differentially expressed genes by microarray
      analysis, from which 20 overlapping genes were identified, and 3 overexpressed
      genes were found with probable metastasis potential, namely the ADM, IRF1, and
      CAV1 genes. Quantitative RT-PCR validated the data mining results in the 5-8F
      EGFP, 6-10B-EGFP, NP69, and 5-8F-LN cell lines. The 3 NPC cell lines 5-8F-EGFP, 6
      10B-EGFP and 5-8F-LN showed significantly higher expressions of IRF1 than NP69
      cells (P=0.008, 0.022, and 0.006, respectively. The expression level of CAV1 in 5
      8F-EGFP cells was significantly higher than that in 6-10B-EGFP cells (P=0.014),
      but ADM expression showed no significant difference between the 4 cell lines.
      CONCLUSIONS: IRF1 may play an important role in the progression of NPC. The
      overexpression of CAV1 in 5-8F-EGFP cells can be associated with the high
      metastatic potential of the cells.

PMID- 18819859
TI  - [Effects of anti-CD25 monoclonal antibody on the level of cytokines in aqueous
      humour after rat penetrating keratoplasty].
AB  - OBJECTIVE: To investigate the toxicity of anti-CD25 monoclonal antibody (mAb) to
      rat cornea and its effects on the cytokines in the aqueous humour after
      penetrating keratoplasty (PKP), thereby evaluating the effect of anti-CD25 mAb in
      preventing corneal allograft rejection. METHODS: The corneal toxicity of anti
      CD25 mAb at 50, 100 and 200 microg administered via subconjunctival injection was
      evaluated in 12 SD rats by histological examination and transmission electron
      microscopy. Another 93 SD rats were randomized into 5 groups, and transplantation
      of corneal allograft from Wistar rats was performed in 4 groups with the other
      group as the normal control. The 4 allograft groups were treated with saline, 100
      microg anti-CD25 mAb, 100 microg anti-CD25 mAb with 50 microg dexamethasone, and
      50 microg dexamethasone, respectively. The graft rejection was observed, the
      aqueous humour levels of IFN-gamma and IL-4 were measured with ELISA, and IFN
      gamma mRNA expressions in the grafts detected with RT-PCR. RESULTS: anti-CD25 mAb
      at 50 or 100 microg did not show significant toxicity on the cornea, but at 200
      microg, the mAb caused swelling of the corneal stromal cells and endothelial
      cells. After corneal allograft transplantation, a significant delay in allograft
      rejection was observed in the 3 groups with mAb or dexamethasone treatment as
      compared with that in saline group (P<0.05). IFN-gamma mRNA expression in the
      allograft on days 11 after PKP and in the aqueous humour on days 6 and 11 was
      markedly increased in saline group compared with that in the 3 treatment groups
      (P<0.05). The mean IL-4 level in the aqueous humour was significantly higher in
      the mAb group than in saline group (P<0.05), but markedly lower in anti-CD25
      mAb+dexamethasone and dexamethasone groups than in anti-CD25 mAb group (P<0.05).
      CONCLUSIONS: Anti-CD25 mAb at 20 and 100 microg does not obviously affect the rat
      corneas. Anti-CD25 mAb inhibits IFN-gamma expression and promotes IL-4 the
      expression to reduce corneal allograft rejection, whereas anti-CD25 mAb with low
      dose dexamethasone inhibits both IFN-gamma and IL-4 expressions to more
      effectively promote the graft survival.

PMID- 18819860
TI  - [Establishment of a tight tetracycline-controlled HCV-C double transgenic mouse
      model].
AB  - OBJECTIVE: To develop a tight tetracycline-controlled HCV-C double transgenic
      mouse model. METHODS: By crossbreeding of ApoE-rtTA-tTS transgenic mice with TRE
      HCV-C transgenic mice, the double transgenic mice were produced in the F1
      generation. The presence of HCV-C and tTS gene in the F1 generation was confirmed
      by PCR, followed by further identification and quantification of the transgene
      using Southern blot hybridization. The expression of HCV-C in the liver of the
      mouse model was detected immunohistochemically. RESULTS AND CONCLUSION: Two
      transgenic mice were obtained, which contained ApoE-rtTA-tTS and TRE-HCV-C genes
      in the genome. Five founders contained HCV-C gene as confirmed by PCR and
      Southern blot hybridization. The tight tetracycline-controlled system may
      facilitate further study of HCV-C gene expression and gene therapy of hepatic
      cellular carcinoma.

PMID- 18819861
TI  - [Enzyme activity during reteplase production phase by recombinant Pichia
      pastoris].
AB  - OBJECTIVE: To study the activities of the key enzymes in reteplase production by
      Pichia pastoris. METHODS: In shaking flasks, a series of samples were maintained
      after methanol induction. The cells were sonicated to prepare cell-free
      suspensions, in which the activities of AOX, FAD, PDC, G-6-PD, ID, alpha-KGD and
      SD were measured. RESULTS: The specific activity of AOX increased during the
      initial 6 h, reaching the maximum of 44.5 U/mg protein. The activity decreased
      quickly between 6 and 24 h, followed by increment in the following 24 h and
      decreased afterwards. The specific activity of FAD increased gradually in the
      initial 48 h and then decreased, with the peak level of 6.72 U/mg protein
      occurred at 48 h. The specific activity of G-6-PD increased at in 2-6 h and 24-48
      h, but decreased in 6-24 h and after 48 h. The specific activity of PDC decreased
      during the initial 6 h and increased slowed afterwards. The specific activities
      of ID, alpha-KGD and SD all showed a rapid decrease in the initial 6 h and a slow
      decrease in 6-24 h. After 24 h, the activity of ID continued to decrease, but the
      other two increased in the following 24 h and then decreased, reaching the
      maximum at 48 h. CONCLUSIONS: According to the changes of these enzyme
      activities, the whole induction phase can be divided into 4 stages: the methanol
      adaptive period in the initial 6 h, the fast growth period between 6 and 24 h,
      the product accumulation period in 24-48 h and the metabolism lag period in 48-72
      h. In the methanol-adaptive period, complete oxidation of methanol is the
      dominant pathway. But in the following two stages, the metabolic pathway shifts
      towards glycolysis and TCA cycle.

PMID- 18819862
TI  - [Effect of nattokinase on restenosis after percutaneous transluminal angioplasty
      of the abdominal artery in rabbits].
AB  - OBJECTIVE: To investigate the effect of nattokinase on intimal hyperplasia in
      rabbit abdominal artery after balloon injury and explore a novel strategy for the
      preventing restenosis after percutaneous transluminal angioplasty. METHODS: Fifty
      six New Zealand rabbits were randomly divided into 7 groups, namely the solvent
      control group, model group, natto extract lavage group, refined nattokinse lavage
      group, intravenous refined nattokinse injection group, clopidogrel group and
      clopidogrel-aspirin group. Balloon injury was induced by inserting the catheter
      through the femoral artery into the thoracic aorta of the rabbits. The platelet
      counts were notad and platelet aggregation was observed, and the abdominal artery
      was taken for pathological analysis. The expressions of MMP-2 and -9 in the
      abdominal artery were detected immunohistochemically. RESULTS: There was no
      significant difference in the platelet counts, platelet aggregation rate or MMP-2
      and -9 expression between the model group and the nattokinse-treated groups
      (P>0.05). The stenosis index in each nattokinse-treated group was significantly
      greater and the neointimal proliferation index smaller than that of the model
      group (P<0.01 or 0.05). CONCLUSION: Nattokinse can inhibit restenosis of rabbit
      abdominal artery after percutaneous transluminal angioplasty, which is
      independent of its actions on the platelet or MMP-2 and -9 expressions.

PMID- 18819863
TI  - [Protective effect of resveratrol on the intestinal mucosal cells in rats with
      severe acute pancreatitis and the mechanism].
AB  - OBJECTIVE: To investigate the protective effect of resvertrol on the intestinal
      mucosal cells in rats with severe acute pancreatitis and explore the possible
      mechanism. METHODS: Twenty-four SD rats were randomly divided into the sham
      operation (SO) group, severe acute pancreatitis (SAP) group and resveratrol
      treated (RES) group. In the SO group, the pancreases were slightly flipped only.
      In the SAP and RES groups, SAP model was established by retrograde injection of
      40 g/L sodium chrolate (1 ml/kg) through the pancreatic duct, and in the latter
      group, resveratrol (10 mg/kg) was given intravenously. Specimens were obtained 6
      h after SAP model establishment and the endotoxin levels in the portal vein was
      determined with turbidimetry to evaluate the effect of resversatrol on the
      intestinal endotoxin translocation in SAP rats. Apoptosis of the mucosal cells
      was detected by TUNEL methods, and the expression of bax and bcl-2 mRNA were
      determined by RT-PCR. The mitochondrial membrane potential of the intestinal
      mucosal cells was measured by confocal microscopy. RESULTS: The endotoxin levels
      in the portal vein were significantly lower in RES group than in SAP group
      (P<0.01). TUNEL assay demonstrated significantly higher apoptotic index of the
      mucosal cells in SAP group than that in RES group (P<0.01). The expression of Bax
      mRNA in the intestinal mucosal cell was significantly higher in SAP group than in
      RES group (P<0.01), whereas the expression of bcl-2 mRNA was significantly lower
      in SAP group (P<0.01). The mitochondrial membrane potential of the intestinal
      mucosal cell was significantly lower in SAP group than in RES group (P<0.01).
      CONCLUSION: Resvertrol can inhibit the apoptosis of the intestinal mucosa cells
      and maintain the integrity of the intestinal barrier to prevent the bacterial and
      endotoxin translocation in SAP.

PMID- 18819864
TI  - [Preliminary study of the association between human thrombospondin and gastric
      cancer].
AB  - OBJECTIVE: To study the possible role of human thrombospondin (hPWTSR) in gastric
      cancer and explore its potential to serve as the target for gastric cancer
      diagnosis and intervention. METHODS: Using pLexA-hPWTSR as the bait, a premade
      pB42AD-based fetal brain cDNA library was constructed to identify the interacting
      proteins. The expression pattern of hPWTSR in gastric cancer tissues and a
      gastric cancer cell line was observed to investigate the correlation between
      hPWTSR expression and the biological behaviors of the tumor. The possibility of
      hPWTSR as a potential gastric cancer marker was evaluated. RESULTS: Fifty-seven
      independent clones were isolated from 107 clones screened. Sequence analysis
      indicated that the 57 positive clones represented the products of 12 genes. A RT
      PCR-based expression pattern revealed that the expression of hPWTSR in gastric
      cancer tissues and a gastric cancer cell line was lower than that in the
      corresponding normal tissues, but no mutations were identified by the subsequent
      sequence analysis. CONCLUSIONS: hPWTSR interacts with adhesion-related proteins
      and tumor-related genes, and its expression is lowered in gastric cancer tissues
      and gastric cancer cell line. hPWTSR might play a role in gastric cancer
      development, especially in metastasis and might be used as a potential gastric
      cancer marker. The exact functions of hPWTSR and its potential clinical value
      still await further study.

PMID- 18819865
TI  - [Effect of Danshen root compound on blood lipid and bone biomechanics in mice
      with hyperlipemia-induced osteoporosis].
AB  - OBJECTIVE: To observe the effects of Danshen root compound (DSC) on blood lipid
      and bone biomechanics in mice with hyperlipemia-induced osteoporosis. METHODS:
      Forty Kunming mice were randomized into 5 equal groups, and were given
      intragastric administration with distilled water (control), lipid emulsion (LE)
      at the daily dose of 5 ml/kg, LE plus simvastatin, LE plus DSC at 5.0 g/kg (DSC-L
      group), and LE plus DSC at 10.0 g/kg (DSC-H group), respectively. Serum TC, TG,
      and HDL-c levels and left femur hydroxyproline, calcium and phosphate contents
      were measured in the rats, with the right femur taken for bone biomechanical
      test. RESULTS: Compared with those in the control group, serum TC, LDL-c and AI
      of the mice increased and HDL-c, Hyp and bone calcium decreased significantly
      (P<0.01) with lowered bone biomechanical properties. Compared with those of the
      LE model group, AI decreased and HDL-c increased significantly in DSC-L and DSC-H
      groups (P<0.01), and the bone biomechanics in DSC-H group was improved.
      CONCLUSION: Long-term intragastric administration of lipid emulsion causes lipid
      metabolic disorder and induces osteoporosis due to hyperlipemia in mice. DSC can
      significantly increase HDL-c and partially prevent the occurrence of osteoporosis
      in mice.

PMID- 18819866
TI  - [Effects of ascorbic acid on relaxation of ex vivo Bufo gastrocnemius during
      sustained isometric contraction].
AB  - OBJECTIVE: To investigate the effect of ascorbic acid (VC) on relaxation of ex
      vivo Bufo gastrocnemius during sustained isometric contraction. METHODS: Dynamic
      tension of the muscle was recorded under constant voltage stimulation within 7.0
      min at 2 s intervals. The rest tension and relaxation rate of the muscle was
      obtained by weighted fitting to the relaxation process of tension <90% of its
      peak with a mono-exponential model to characterize the muscular relaxation.
      RESULTS: VC at 2.0 mmol/L alone or in combination with the inhibitors of the
      antixoidation enzymes (surperoxide dismutase, glutathione peroxidase and
      catalase) resulted in negligible alterations in the muscular relaxation kinetics.
      VC combined with the inhibitor of surperoxide dismutase resulted in significantly
      lowered relaxation rate while increased rest tension, but VC with the inhibitor
      of either catalase or glutathione peroxidase showed negligible action. VC
      combined with the inhibitors of all the 3 enzymes also caused significant effect
      on the muscular relaxation kinetics, which was similar the effect of VC with
      superoxide dismutase inhibitor. CONCLUSION: VC at high concentration may result
      in oxidative toxicity to the biological system rich in transitional metal ion
      complexes but with low antioxidation capacity by causing superoxide-mediated
      oxidative damages.

PMID- 18819867
TI  - [Plasmid-mediated miRNA-1-2 specifically inhibits Hand2 protein expression in
      H9C2 cells].
AB  - OBJECTIVE: To construct an eukaryotic expression vector for miRNA-1-2 that can be
      expressed in rat H9C2 cardiomyocytes. METHODS: The precursor miRNA (pre-miRNA)
      DNA template for miRNA-1-2 was designed and generated by PCR amplification. The
      DNA template was inserted into the hairpin RNA expression vector pSilence-4.1-neo
      and identified by DNA sequencing analysis. The recombinant plasmid DNA was then
      transfected into H9C2 cells via Lipofectamine, and the green fluorescence protein
      expression vector pEGFP-N3 served as the transfection marker. Twenty-four hours
      after transfection, the total cellular RNA was extracted using TRIzol reagent,
      and thermoscript reverse transcriptase (RT)-PCR was performed to determine miRNA
      1-2 precursor expression. RESULTS AND CONCLUSION: DNA sequencing indicated that
      the miR-1-2 expression plasmid was correctly constructed. The precursor miRNA-1-2
      was successfully expressed in the H9C2 cells, and the expression of Hand2 protein
      could be efficiently inhibited by miRNA-1.

PMID- 18819868
TI  - [Pretreatment of donor dendritic cells with NBD-peptide prolongs mouse cardiac
      allograft survival].
AB  - OBJECTIVE: To observe the effects of NBD-peptide pretreatment of the donor
      dendritic cells in immune tolerance induction in mouse allograft recipients and
      investigate the mechanisms. METHODS: BALB/c mouse DCs pretreated with NBD-peptide
      (NBD-Peptide-DC) were injected into the recipient C57BL/6 mice 7 days before
      transplantation. Cervical heterotopic heart transplantation model was established
      using the cuff technique and the cardiac allograft survival time was observed.
      Pathological analysis were performed to examine the graft injection and the
      responsiveness of the recipient spleen T cell to the donor alloantigen was
      determined by mixed lymphocyte reaction (MLR). The serum levels of cytokines were
      determined using ELISA. RESULTS: The cardiac allograft survival time in the NBD
      Peptide-DC-treated group (21.83-/+3.54 days) was significantly longer than that
      in the Day9-DC group (13.33-/+2.58 days) and PBS-treated group (6.66-/+1.21 days)
      (P<0.01), with also significantly lower pathological grade for graft rejection
      (P<0.01). The donor-derived NBD-Peptide-DCs induced alloantigen-specific T-cell
      hyporesponsiveness. In the NBD-Peptide-DC-treated group, the serum levels of IL
      12 and IFN-gamma decreased significantly (P<0.01), but the levels of IL-4 and IL
      10 increased significantly (P<0.01). CONCLUSION: Injection of donor-derived NBD
      Peptide-DCs can leads to donor-specific tolerance in the transplant recipients,
      and the induction of recipient T-cell hyporesponsiveness and polarization of Th2
      response may play important roles in immune tolerance to cardiac allografts.

PMID- 18819869
TI  - [In vitro drug release from a mitomycin C delivery system and its effect against
      scar tissue adhesion in vivo].
AB  - OBJECTIVE: To develop a chitosan (CH)/polyethylene glycols succinate acid (PEG
      SA)-mediated mitomycin C (MMC) delivery system and investigate its drug release
      characteristics in vitro and its effect against scar tissue adhesion in vivo.
      METHODS: Mitomycin C loading in the composite CH/PEG-SA/MMC films was determined
      using ultraviolet. The freeze-dried films were dispersed in 1 ml PBS (pH7.4) and
      mitomycin C release in vitro was determined according to the mitomycin C
      concentration-UV value standard curve. The influence of the film structure on the
      drug release was evaluated. The drug delivery system was then implanted in SD
      rats, and 4 weeks later, immunohistochemical and histological examinations were
      carried out to assess the therapeutic effect on epidural scar tissue. RESULTS:
      The linear regression equation of the mitomycin C concentration-UV value standard
      curve was y=0.593x(3)-2.563x(2)+25.944x-0.236 (R(2)=1.000). The film demonstrated
      good drug delivery capability, and 20 mg of the samples in PBS showed a peak
      mitomycin C release after 12 days of 14.9616 microg/ml, which was higher than the
      ID(50) of mitomycin C (10.4713 microg/l) to the fibroblasts. On days 18 and 32,
      another two drug release peaks occurred (14.4824 microg/ml and 11.4092 microg/ml,
      respectively), followed by maintenance of slow release. Till day 60, the
      accumulative mitomycin release reached 0.1793 microg/ml, and the loaded drug was
      ultimately completely released. Significant differences were noted in the
      hydroxyproline content in the scar tissues of different groups (F=12.085,
      P=0.000), and the CH/PEG-SA/MMC DDS reduced the amount of scar tissue and
      promoted its orderly alignment to control potential scar hyperplasia that may
      compress the spinal cord and nerve roots. CONCLUSION: The composite film for drug
      delivery possesses good flexibility and mechanical properties and allows
      sustained drug release of mitomycin C to prevent epidural scar tissue adhesion
      following lumbar laminectomy.

PMID- 18819870
TI  - [Optimization of the scan delay time of 64-slice spiral CT portal venography].
AB  - OBJECTIVE: To optimize scan delay time of multi-slice spiral CT portal venography
      (MSCTP) using test bolus injection. METHODS: Sixty individuals with no hepatic
      diseases were randomly divided into 4 groups (A, B, C and D). The time-density
      curves (TDC) of the portal vein (PV) were acquired by test bolus (15 ml, 5 ml/s)
      at the level of liver hilus. In the 4 groups, the MSCTP were delayed for 4, 6, 8
      and 10 s according to the peak time of TDC, respectively. The maximum CT value of
      the portal vein and liver parenchyma were recorded. The maximum intensity
      projection (MIP) and volume rendering (VR) were employed for three-dimensional
      reconstruction and the image quality of the 4 groups was estimated. RESULTS: The
      average peak time of healthy individuals ranged between 24 and 32 s (95%
      confidence interval) by means of the test bolus (15 ml). Group C (delay time of 8
      s) had a much better image quality of the portal vain than the other groups, and
      the small branches of the portal vein (6th and 7th orders) were clearly
      visualized; the major portal vein branches (1st to 4th orders) were also enhanced
      with sharp edges. Although the hepatic vein was also observed in the portal
      venous phase in group D, the details of the portal vein on the hepatic edge were
      distinct and well defined. CONCLUSION: At the injection rate of 5 ml/s, the
      optimum scan time delayed is 8 to 10 s in normal individuals according to the
      peak time of the test bolus.

PMID- 18819871
TI  - [Establishment of a mouse model of biliary obstruction and its dynamic
      observations].
AB  - OBJECTIVE: To establish a mouse model of biliary obstruction. METHODS: Sixty-four
      Balb/c mice were divided into experimental group and control group. Obstructive
      jaundice was induced in the mice in the experimental group by common bile duct
      ligation. The level of the common bile duct diameter, WBC, LYM MID, LYM%, MID%
      and ALT, AST, TBIL, DBIL, IBIL, ALP and CHOL were measured 12 h and 1, 2 ,3, 4,
      5, and 7 days after the ligation. The morphological changes in the liver were
      also observed. RESULTS: The level of common bile duct diameter, WBC, LYM, MID,
      LYM%, MID% and ALT, AST, TBIL, DBIL, ALP and CHOL all underwent changes with time
      following certain patterns. CONCLUSION: The jaundice manifestation of this model
      is similar to that of patients with biliary obstruction, and this model may
      provide a reliable model for studying the mechanism of obstructive jaundice.

PMID- 18819872
TI  - [Transcriptional regulation of genes involved in liver-selective cell
      communication].
AB  - OBJECTIVE: To explore the mechanism of transcription regulation of the liver
      selective genes responsible for cell communication. METHODS: Tissue-selective
      Affymetrix probe sets (3919 probes in total) were clustered by functional
      categories. Liver-selective cell communication (LSCC) genes were selected for
      further analysis. The 500-bp upstream sequences of all the LSCC genes were
      extracted for predicting the transcription factor binding sites (TFBS) of known
      transcription factors (TFs) using 3 programs; literature mining was then
      performed for these LSCC genes and TFs, and the transcription regulatory network
      were constructed. RESULTS: The binding sites of 50 and 72 transcription factors
      were predicted from the upstream sequences of 23 LSCC genes by two programs
      respectively. Among them, 18 transcription factors were found in common. The top
      10 TFBS sequences were basically consistent to the predicted TFs. Literature
      mining indicated that LSCC genes and TFs were closely related to such terms as
      albumin, diabetes, glucose, lipid, metabolism, and JNK, in addition to those
      associated with hepatic tissue and TFs. These observations suggested that LSCC
      genes and TFs were involved in the regulation of glucose and lipid metabolism,
      binding and transport, coagulation signal cascades, inflammatory response, etc.
      PPP2R1B, which was out of the network, showed a partial functional similarity to
      DUSP10 in the network. CONCLUSIONS: LSCC genes and the predicted TFs may be
      involved in the regulation of many important functions of the liver, which are
      integrated into a sophisticated transcription regulatory network. JUN may be the
      key target for regulation, and PPP2R1B is presumed to participate in the
      regulation of JUN.

PMID- 18819873
TI  - [Evaluation of allogenic complement-regulating proteins in the peripheral blood
      cells of chimeric rat models harboring human cord blood stem cells].
AB  - OBJECTIVE: To analyze the mechanisms of surrogate tolerogenesis induced by
      chimeric donors. METHODS: Hematopoietic stem cells (HSCs) from human cord blood
      were transplanted into fetal rats via intrauterine injection and infused into the
      liver of the neonatal rats to establish chimeric rat models with human HSCs. Four
      weeks after birth, flow cytometry was performed to analyze the percentages of
      human CD45 (hCD45), CD55 (hCD55) and CD59 (hCD59)-positive cells in the
      peripheral blood cells of the chimeric rats. The distributions of hCD55- and
      hCD59-positive cells in different hCD45/SSC gating regions were observed. The
      resistance of the peripheral blood lymphocytes to complements-mediated cytolysis
      was assessed by complement-dependent cytotoxicity (CDC) test in the chimeric rats
      and compared with that in control rats. The correlation between CDC and the human
      complement-regulating proteins in the chimeric rats were analyzed statistically.
      RESULTS: On hCD45/SSC gating, the percentages of hCD55- and hCD59-positive cells
      in hCD45-positives region were (53.69-/+18.23)% and (31.8-/+27.5)%, accounting
      for (2.0-/+1.32)% and (0.76-/+0.56)% of the total cell population, respectively,
      which were significantly lower than the cell percentages in the extensive region
      (t=2.71, P=0.043 and t=3.64, P=0.015). The cytolytic rate of PBLs incubated with
      normal human serum was (22.32-/+15.10)% in the chimeric rats, significantly lower
      than that in the non-chimeric rats [(60.7-/+22.65)%, t=4.16, P<0.001). In the
      chimeric rats, hCD55-positive cell percentage was inversely correlated in the
      peripheral blood karyocytes the cytolysis rate in CDC (r=-0.679, P=0.031), and
      positively correlated to hCD45-positive cell percentage (r=0.658, P=0.038).
      CONCLUSION: The hCD45-positives region is the cluster of chimeric human cells
      expressing human complement-regulating proteins. The peripheral blood lymphocytes
      from chimeric donor can resist the cytolysis mediated by human complement. The
      presence of allogenic CD55 and CD59 antigens in chimeric donors may be the basis
      of surrogate tolerogenesis for xenotransplantation.

PMID- 18819874
TI  - [A fast 3-D medical image registration algorithm using principal component
      analysis].
AB  - This paper presents a new 3-D image registration method based on the principal
      component analysis (PCA). Compared with intensity-based registration methods
      using the whole volume intensity information, our approach utilizes PCA to
      estimate the centroid and principal axis, and completes the registration by
      aligning the centroid and principal axis. We evaluated the effectiveness of this
      approach by applying it to simulated and actual brain image data (MR, CT, PET,
      and SPECT). The experimental results indicate that the algorithm is effective,
      especially for registration of 3-D medical images.

PMID- 18819875
TI  - [Ginsenoside Rg1 modulates COX-2 expression in the substantia nigra of mice with
      MPTP-induced Parkinson disease through the P38 signaling pathway].
AB  - OBJECTIVE: To investigate the role of P38 signaling pathway in modulating the
      expression of cyclooxygenase-2 (COX-2) in the substantia nigra (SN) of mice with
      1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced Parkinson disease
      (PD), and explore the possible mechanism of the dopaminergic (DA) neuron death in
      PD and the effects of ginsenoside Rg1 on the P38 signaling pathway and DA
      neurons. METHODS: C57BL6 mice were treated with MPTP to produce the subacute PD
      model, and the behavioral changes were observed. Immunohistochemistry and Western
      blotting for tyrosine hydroxylase (TH), COX-2, prostaglandin E2 (PGE2) and
      phosphorylated P38 (p-P38) were used to observe the changes of positive cell
      number in the midbrain after treatment with ginsenoside Rg1. RESULTS: Compared
      with the control mice, the mice with PD presented with typical symptoms of PD.
      The number of p-P38-, COX-2-, and PGE2-positive cells significantly increased in
      the SN area 6 h after the 3rd injection of 30 mg/kg MPTP (P<0.01). The number of
      TH-positive neurons in the PD model group was substantially reduced by about 60%
      (P<0.01) in 24 h after the 5th injection of MPTP. In mice with ginsenoside Rg1
      treatment, the number of p-P38-, COX-2-, and PGE2-positive cells was reduced
      obviously 6 h after the 3rd injection of MPTP as compared with that in the model
      group (P<0.01). The number of TH-positive neurons in the SN was decreased by only
      30% (P<0.01 vs control group) 24h after the 5th injection of MPTP. CONCLUSION:
      P38 signaling pathway may play an important role in modulating COX-2 expression
      in the SN in the early stage of MPTP-induced subacute PD, and ginsenoside Rg1 may
      act on the P38 signaling pathway to protect the DA neurons in PD.

PMID- 18819876
TI  - [FOLFOX versus PLF regimen in treatment of advanced gastric adenocarcinoma].
AB  - OBJECTIVE: To compare the efficacy and tolerability of the regimen FOLFOX
      [1eucovorin (LV), 5-fluorouracil (5-Fu) and oxaliplatin] and the regimen PLF
      (Paclitaxel, leucovorin and 5-Fu) for treatment of advanced gastric
      adenocarcinoma. METHODS: We retrospectively studied the clinical data of 132
      patients with stage IV gastric adenocarcinoma treated by FOLFOX (group A, n=60)
      or PLF (group B, n=72). The tumor response rate, toxicity, time to progress (TTP)
      and overall survival (OS) were compared between the two groups. RESULTS: A total
      of 544 cycles were administrated in these patients. The overall response rate was
      35.0% with FOLFOX regimen and 41.7% with PLF regimen, showing no significant
      difference between them (P>0.05). The TTP was 6.13-/+1.26 (95%CI, 3.65-8.61)
      months in group A, and 5.92-/+0.49 (95%CI, 4.97-6.87) months in group B; the OS
      was 10.67-/+1.55 (95%CI, 7.63-13.71) months in group A, and 10.8-/+3.07 (95%CI,
      4.78-16.82) months in group B. Neither TTP or OS showed significant differences
      between the two groups (P>0.05). Five patients in group A (8.33%) and 8 in group
      B (11.11%) had grade 3 and 4 leukopenia. The non-hematological toxicities were
      mostly mild, including nausea, vomiting, stomatitis, diarrhea and alopecia. The
      main adverse effects were grade 1 or 2 sensory neuritis in FOLFOX group, and
      alopecia in PLF group, without significant difference between the two groups
      (P<0.05). CONCLUSION: Both FOLFOX and PLF can serve as effective first-line
      treatment of stage IV gastric adenocarcinoma with good tolerance.

PMID- 18819877
TI  - [Effect of small interfering RNA-mediated silencing of CD158b expression on the
      cytotoxicity of NK cells against the allogeneic dendritic cells].
AB  - OBJECTIVE: To study the effects of small interfering RNA (siRNA)-mediated
      silencing of CD158b expression on the efficiency of the natural killer (NK) cells
      in killing allogeneic dendritic cells. METHODS: After the knockdown of CD158b by
      CD158b -SiRNA, the CD158b mRNA expression in natural killer cells was examined by
      qRT-PCR and the CD158b protein expression by flow cytometer. The cytotoxic
      activity of RNAi-NK cells and normal NK cells against the allogeneic dendritic
      cells was detected by LDH release assay. RESULTS: The CD158b mRNA expression and
      its protein expression were decreased significantly in the NK cells by CD158b
      siRNA (P/0.05). The cytotoxic activities of alloreactive NK cells generated by
      RNAi CD158b expression against allogeneic dendritic cells were increased
      significantly. CONCLUSION: Silencing CD158b gene can inhibit the NK cell CD158B
      mRNA and protein expression. Alloreactive NK cells generated by RNAi CD158b
      expression have the potential for use in interventions of GVHD.

PMID- 18819878
TI  - [Effect of porcine relaxin on NO production of human microvascular endothelial
      cells].
AB  - OBJECTIVE: To observe effect of porcine relaxin(pRLX) on NO production of human
      microvascular endothelial cells(HMVECs) and discuss its possible mechanism.
      METHODS: iNOS and cNOS expression of HMVECs with or without pRLX were detected
      using western blotting. NO production of HMVECs with pRLX at different
      concentration or different time were determined by method of Griess. NO
      production of pRLX of HMVECs plus Non-selective NOS inhibitor NG-monomethyl-L
      arginine(L-NMMA), selective iNOS inhibitor aminoguanidine(AG) or nuclear factors
      kappaB (NF-kappaB) inhibitor pyrrolidine dithiocarbamate(PDTC) were also
      analysed. RESULTS: pRLX promoted iNOS protein expression of HMVECs, but not cNOS
      protein expression. NO production of HMVECs was promoted by pRLX on concentration
      dependent pattern instead of time-dependent one. AG, L-NMMA and PDTC were showed
      to block the effect of pRLX on NO production of HMVECs. CONCLUSION: pRLX promote
      iNOS expression and NO production of HMVECs.

PMID- 18819879
TI  - [In vitro proliferation of CD4(+)CD25(+) T cells from PBMCs of the chronic
      myelocytic leukemia patients and their inhibitory effect on CD4(+)CD25(-) T
      cells].
AB  - OBJECTIVE: To investigate the in vitro proliferation of CD4(+)CD25(+) T cells
      from the peripheral blood mononuclear cells (PBMCs) of the chronic myelocytic
      leukemia patients and the inhibitory effect on CD4(+)CD25(-) T cells. METHODS:
      Magnetic-activated cell sorting (MACS) was used to separate CD4(+)CD25(+) T and
      CD4(+)CD25(-) T cells from the PBMCs of patients with chronic myelocytic
      leukemia, and the purity and activity of CD4(+)CD25(+) T cells were analyzed with
      flow cytometry. After stimulation with anti-CD3 mAb, anti-CD28 mAb and
      recombinant human interleukin-2 (rhIL-2), the CD4(+)CD25(-) and CD4(+)CD25(+) T
      cells were cocultured to observe the inhibitory effect of CD4(+)CD25(+)T on
      CD4(+)CD25(-)T cells using MTT assay. RESULTS: After cell sorting, the purity of
      CD4(+)CD25(+)T cells from healthy control and chronic myelocytic leukemia
      patients were (84.93-/+2.55)% and (86.32-/+2.40)%, respectively, showing no
      significant difference between them (P>0.05). The activity of CD4(+)CD25(+) and
      CD4(+)CD25(-) T cells from healthy control and the leukemic patients was also
      comparable [(98.12-/+0.68)% vs (97.33-/+0.78)%, P>0.05). In the coculture,
      CD4(+)CD25(+) T cells obviously inhibited CD4(+)CD25(-) T cell proliferation in
      vitro, and the maximum inhibition occurred when CD4(+)CD25(+)T cells were
      cocultured with CD4(+)CD25(-)T cells at the ratio of 1:1. CONCLUSION: The MACS
      system can effectively isolate CD4(+)CD25(+) and CD4(+)CD25(-) T cells.
      CD4(+)CD25(+) T cells obviously inhibit the proliferation of CD4(+)CD25(-)T cells
      in vitro, and the effect displays an effector-target ratio relationship.

PMID- 18819880
TI  - [Construction and expression of a prokaryotic vector of recombinant human
      adiponectin global domain].
AB  - OBJECTIVE: To construct and express the recombinant human adiponectin (gAd)
      global domain. METHODS: gAd complementary DNA (cDNA) was obtained from human fat
      tissue by RT-PCR. The PCR product was cloned into the vector pMD18-T and the
      prokaryotic expression vector pET32a(+). The recombinant vector was identified by
      digestion with double restriction endonucleases SalI and EcoRI, PCR and sequence
      analysis. The recombinant plasmid containing gAd gene was transformed into E.
      coli BL21 (DE3), and the expression of the fusion protein His-gAd was induced by
      IPTG. RESULTS: The gAd cDNA of 412 bp was obtained from the total RNA of the fat
      tissue and verified by sequence analysis. CONCLUSION: The recombinant plasmid
      could stably express the 34-kD fusion protein His-gAd in the engineered bacteria
      in the form of inclusion bodies.

PMID- 18819881
TI  - [Construction of a recombinant adenovirus expression vector for human renal tumor
      associated antigen G250 gene with AdMax system].
AB  - OBJECTIVE: To construct a adevoviral vector harboring human renal tumor
      associated antigen G250 gene for transfecting the dendritic cells (DCs) and
      treating renal tumors. METHODS: The G250 genes were cloned into the shuttle
      plasmid pDC316 to construct pDC316-G250, which was cotransfected with the rescue
      plasmid pBHGlox(delta)E1,3Cre into 293 cells to obtain the recombinant adenovirus
      Ad/G250. The inserted gene and its expression were identified by RT-PCR and
      fluorescence-activated cell sorting (FACS) after recombinant adenovirus
      transfection of the DCs. The recombinant adenoviral vector was purified by CsCl
      banding and titrated by TCID50. RESULTS AND CONCLUSION: The recombinant
      adenoviral vector of G250 gene was successfully constructed and high titer of the
      recombinant adenoviruse was obtained. G250 mRNA and protein expressions were
      identified in Ad/G250-transfected DCs. The titer of the virus stocks reached
      5.6x10(9) IU/ml.

PMID- 18819882
TI  - [Anti-tumor and bystander effects of cationic liposome-mediated CD/5-FC suicide
      gene system combined with interferon-gamma in vivo].
AB  - OBJECTIVE: To study the antitumor and distant bystander effects of cationic
      liposome-mediated cytosine deaminase (CD)/5-fluorocytosine (5-FC) suicide gene
      system combined with interferon-gamma (IFN-gamma) in vivo. METHODS: Murine
      hepatoma 22 (H22) cells transfected by CD gene were inoculated subcutaneous in
      Kunming mice in the left axillary region, and the H22 cells without CD gene
      transfection were inoculated in the right axillary region. The mice were randomly
      divided into 4 groups and treated with normal saline , 5-FC, IFN-gamma, and 5-FC+
      IFN-gamma on a daily basis. The tumor inhibition and distant bystander effects
      were observed in the mice. RESULTS: Exposure of CD gene-transfected tumor to 5-Fc
      resulted in obvious tumor growth inhibition with an inhibition rate of 78.38%,
      which was significantly increased to 93.21% (P<0.01) with 5-Fc +IFN-gamma
      treatment. A notable distant bystander effect in the CD/5-FC suicide gene system
      was observed in vivo, with a tumor inhibition rate of was 54.42%; when combined
      with IFN-gamma, the inhibition rate increased significantly to 87.57% (P<0.05).
      CONCLUSION: When combined with IFN-gamma, CD/5-FC suicide system has stronger
      anti-tumor and distant bystander effects. CD/5-FC suicide gene system combined
      with IFN-gamma may provide a potential therapy for malignant tumors.

PMID- 18819883
TI  - [Study of the bacterial community structure of microbiota in bacterial vaginosis
      using amplified ribosomal DNA restriction analysis].
AB  - OBJECTIVE: To study the bacterial community structure of the microbiota in the
      vaginal fluid from patients with bacterial vaginosis. METHODS: The composition of
      bacteria in the samples of vaginal fluid from 3 patients with bacterial vaginosis
      and 1 normal premenopausal control was investigated by amplified ribosomal DNA
      restriction analysis(ARDRA). RESULTS: Lactobacillus species were the predominant
      bacteria in the woman without bacterial vaginosis. Bacterial vaginosis was
      associated with higher concentrations of a variety of bacterial groups. Women
      with bacterial vaginosis had greater bacterial diversity, with 31 to 37 OTUs
      operational taxonomic units detected per sample. The species associated with
      bacterial vaginosis were Leptotrichia, Prevotella sp. and Megasphaera including
      several species with no close cultivated relatives. CONCLUSIONS: Women with
      bacterial vaginosis have complex vaginal infections with many newly recognized
      species. ARDRA allows rapid analysis of the diversity of microorganisms in the
      vagina, and is capable of identifying potentially pathogenic bacteria that can
      not be identified by general culture.

PMID- 18819884
TI  - [Construction of a recombinant eukaryotic vector of human intestinal trefoil
      factor and its expression in 293-T cells].
AB  - OBJECTIVE: To clone human intestinal trefoil factor (hITF/hTFF3) gene into an
      eukaryotic expression vector for its expression in eukaryotic cells. METHODS: The
      total RNA was extracted from normal human colon mucosa, and transcribed into
      cDNAs using RT-PCR. hTFF3 gene was amplified by PCR and ligated into pGEMT vector
      by TA cloning method. After sequencing, the hTFF3 gene was transfered into the
      eukaryotic expression vector pCMV5-myc. The recombinant vector was transfected
      into 293-T cells, and the expression of the recombinant protein was detected by
      Western blotting. RESULTS AND CONCLUSION: hTFF3 gene was successfully cloned from
      normal human colon mucosa. The vector pCMV5-myc-hTFF3 was reconstructed, and in
      293-T cells transfected with the vector, hTFF3 expression was detected by Western
      blotting.

PMID- 18819885
TI  - [Effect of ketoconazole on the activity of CYP4503A4 and CYP450 1A2 of hepatic
      microsomes in healthy adults].
AB  - OBJECTIVE: To observe the effect of ketoconazole on the activity of cytochrome
      P450 (CYP) 1A2 and 3A4 in hepatic microsomes of healthy adults. METHODS: Human
      hepatic microsomes obtained from healthy adults were randomly divided into
      control group and ketoconazole-treatment groups at different concentrations.
      After 15 min of culture, the substrates (testosterone for CYP3A4 and phenacetin
      for CYP1A2) were added and incubated for another 20 min. The metabolites (6
      testosterone and acetaminophen) were then measured with high-performance liquid
      chromatography (HPLC) to assess the activities of CYP3A4 and 1A2. RESULTS:
      Significant difference was found between the groups in the quantity of 6
      testosterone and the relative activity of CYP3A4 (P<0.05). The IC(50) of
      ketoconazole for CYP3A4 was 0. 16 mg/L. Both the quantity of 6-testosterone and
      the relative activity of CYP3A4 were reduced gradually with the increment of
      ketoconazole concentration. Significant differences were found between the
      ketoconazole groups and the control group in both the quantity of acetaminophen
      and the relative activity of CYP1A2 (P<0.05). Ketoconazole at low doses reduced
      CYP1A2 activity and but increased the activities at high doses (P<0.05).
      CONCLUSION: In the range of maximum clinical blood concentration, ketoconazole
      can inhibit the activity of CYP3A4, but not that of CYP1A2, in the hepatic
      microsomes in healthy adults.

PMID- 18819886
TI  - [Sedative, hypnotic and antiseizure effects of compound gardenia oil and jujube
      seed oil in mice].
AB  - OBJECTIVE: To study the sedative, hypnotic and antiseizure effects of the
      compound preparation of gardenia oil and jujube seed oil in mice and investigate
      the interaction of the two drugs in this preparation. METHODS: The compound
      preparation was administered intragastrically in mice, whose spontaneous activity
      was observed along with their tolerance of the preparation after long-term
      administration. The hypnotic effect of the compound was assessed by investigating
      the changes in the pentobarbital sodium-induced sleeping. The compound was tested
      for its antiseizure effect in mice with pentetrazole-induced clonic and tonic
      convulsion. Diazepam was used as the standard control in all experiments.
      RESULTS: The jujube seed oil, the gardenia oil and their compound all inhibited
      spontaneous activities of the mice. Compared with diazepam, the compound showed
      slow action in producing the sedative effect, which increased gradually with
      prolonged drug administration without obvious drug tolerance responses. The
      compound and the two oils all showed synergistic action with pentobarbital sodium
      in inducing sleeping of the mice. Prescription study showed that the compound
      produced stronger sedative and hypnotic effects than either of the oils. The two
      oils and the compound did not show significant antiseizure effects in mice.
      CONCLUSION: The compound of jujube seed oil and gardenia oil has sedative and
      hypnotic effects in mice, and the two oils in the compound show obvious
      synergistic effect.

PMID- 18819887
TI  - [Relationship between reference point potential and potential distribution of
      normal electrocardial field on the thoracic surface of healthy individuals].
AB  - OBJECTIVE: To explore the effect of reference point on the potential distribution
      of normal cardioeleclric field of healthy individuals. METHODS: Two different
      reference points including central terminal and right forehead were applied to
      record electrocardiogram simultaneously from 15 testing points (V(1)-V(6), V(7)
      V(9), V(3R)-V(8R)) of Wilson lead (RL) and the same testing points (HV(1)-HV(9),
      HV(3R)-HV(8R)) of head-chest (HC) lead around the torso of healthy individuals.
      Chi-square test was performed to observe statistical difference between the
      HCECGs and RLECGs according to different shapes of QRS and T waves. RESULTS:
      Among 120 healthy individuals, deformed ECGs appeared in V(1) and HV(3R)-HV(8R)
      leads, with 20% (24/120) inverted T wave in V(1) lead, 100% (120/120) in V(3R)
      V(8R) leads, wide or deep Q wave 100% (120/120) in V(4R)-V(8R) leads. However, in
      the corresponding HC-lead system, T waves were all positive, and QRS waves were
      upright as the pattern of rs, RS or qRs. There was statistical difference in the
      form of ECG between V(1), V(3R)-V(8R) of Wilson lead and the corresponding HC
      lead (P<0.05). The distribution of normal cardioeleclric field related to QRS-T
      wave was of all-round outward shape by HC-lead, and of roughly bipolar shape by
      Wilson lead for inverted QRS-T wave on the right thoracic surface. CONCLUSION:
      The normal distribution of electrocardial field is determined by the potential of
      the reference point. The forehead of HC-lead seems to be better than the central
      terminal as the reference point of the lead system.

PMID- 18819888
TI  - [Effect of rosiglitazone on tumor necrosis factor-alpha-induced nuclear factor
      kappaB and coupling factor 6 expressions in human umbilical vein endothelial
      cells].
AB  - OBJECTIVE: To investigate the effect of rosiglitazone on the expression of
      nuclear factor-kappaB (NF-kappaB) and coupling factor 6 (CF6) induced by tumor
      necrosis factor-alpha (TNF-alpha) in cultured human umbilical vein endothelial
      cells (HUVEC). METHODS: Cultured HUVEC of passage 3-5 were stimulated with TNF
      alpha and then cultured in the presence of rosiglitazone. The expression of CF6
      and NF-kappaB subunit p65 were evaluated by immunocytochemistical method.
      RESULTS: Pretreatment of HUVECs with rosiglitazone inhibited TNF-alpha-induced
      expression of CF6 in a dose-dependent manner. The activation of CF6 stimulated by
      TNF-alpha was suppressed by ROS in a dose-dependent manner. CONCLUSION: TNF-alpha
      induced enhancement of the gene expression and release of CF6 is mediated by
      activation of NF-kappaB signaling pathway. ROS can inhibit the activation of IKK,
      block NF-kappaB signaling pathway and inhibit the expression of CF6, which may be
      the mechanism underlying the action of TZDs on hypertension.

PMID- 18819889
TI  - [Dynamic finite element analysis of three ferrule designs in post crown under
      impact loading].
AB  - OBJECTIVE: To investigate the stress distribution in three ferrule designs in a
      maxillary central incisor restoration using PFM crown with post, and evaluate the
      biomechanical mechanism of the ferrule effect in the post crown by 3D finite
      element dynamic analysis. METHODS: The 3D finite element model of a maxillary
      central incisor restored with post and PFM crown was established. By simulating
      three types of ferrule effect [crown wrapping dentine (A), core collar wrapping
      (B), and contrabevel (C)] under dynamic loading, the dentin stress was analyzed.
      RESULTS: During dynamic loading, the stress distribution tended to increase from
      the cervical part to root middle and radical part of the tooth, and greater high
      stress area was found around the apex of the post, where the peak stress was
      observed value. The stress of the labial dentin of the root inferior segment
      increased obviously. The high stress areas were invariable at every loading step
      during dynamic loading. The peak stress was sigma(vonA)<sigma(vonC),
      sigma(vonB)<sigma(vonC), (P<0.05). The contrabevel had the minimal effect in
      decreasing the peak stress. CONCLUSIONS: When the ferrule is 2 mm, the ferrule
      effect maintained by crown wrapping cervical dentine (A) and core collar wrapping
      (B) is greater than that maintained by contrabevel (C),but there is no
      significant difference between A and B. The post with higher elastic modules may
      cause restore failure due to the high stress at the post apex and labial dentin.

PMID- 18819890
TI  - [Changes of hair papilla and its role in the growth cycle of the hair follicles].
AB  - OBJECTIVE: To investigate the changes of hair dermal papilla and its regulatory
      role in the growth cycle of the hair follicles. METHODS: Single hair follicles
      were isolated from surgical specimens of human scalp and cultured in Williams E
      medium. The growth of the hair follicle was measured and the morphology and
      structure of the dermal papilla in the different growth cycles were observed
      continuously. RESULTS: The hair follicle could grow in the medium for 12 days at
      the average growth rate of 0.2-0.3 mm/day. The flat and round dermal papilla lay
      at the bottom of the hair bulb in the telogen and anagen stages. In the hair
      follicle with accelerated growth, the dermal papilla became elongated, loosened,
      and closely adhered to the hair matrix. In the catagen stage the dermal papilla
      shrunk, and became separated from the hair matrix. A new hair bulb was
      regenerated when the hair follicle was transected at a low level. The hair
      follicle stopped growing after transection at a higher position. CONCLUSION: The
      hair dermal papilla is the essential for hair follicle growth, and plays an
      important role in regulating the hair growth cycle.

PMID- 18819891
TI  - [Relationship between apolipoprotein e4 allele and emergence agitation in
      patients undergoing general anesthesia].
AB  - OBJECTIVE: To investigate the relationship between apolipoprotein e4 allele and
      emergence agitation (EA) in patients undergoing general anesthesia. METHODS: A
      nested cohort study was conducted in elderly patients (over 60 years old)
      scheduled for major abdominal surgery requiring general anesthesia. A structured
      interview was conducted in PACU to determine EA, defined using the Sedation
      Agitation Scale (SAS). Blood samples were obtained for measurement of the
      apolipoprotein genotypes. RESULTS: Of the 196 patients studied, 22.4% developed
      EA. Thirty-eight patients (19.4%) had the apolipoprotein e4 allele. The presence
      of the e4 allele and low level of education were both associated with an
      increased risk of EA (36.9% vs15.8%, P=0.005; 30% vs 14.3%, P=0.01). After
      adjustment for covariates, the patients with the copy of e4 allele were shown to
      have a greater likeliness of an increased risk of EA (odds ratio: 4.32; 95% CI:
      1.75-10.05) than those without the e4 allele. CONCLUSION: Apolipoprotein e4
      carrier status is associated with an increased risk for EA.

PMID- 18819892
TI  - [Preparation of VX2 rabbit hepatoma models and modification of the hepatic artery
      catheterization technique].
AB  - OBJECTIVE: To establish New Zealand rabbit hepatoma models with VX2 cell line,
      and modify the hepatic artery catheterization technique. METHODS: Forty New
      Zealand rabbit models bearing hepatoma were established by implanting VX2 cells
      into the left and right liver lobes. Two weeks after the tumor cell implantation,
      26 rabbits in the experimental group underwent modified hepatic artery
      catheterization procedures using microsurgical technique, and 10 rabbits in the
      control group were catheterized with 3F micro-catheter using Seldinger technique.
      The VX2 hepatomas were observed before and after the catheterization with multi
      slice spiral CT scan and digital subtractive angiography (DSA). RESULTS: Tumor
      growth after the tumor cell implantation was confirmed in 36 rabbits by CT scans
      and open operations. The success rate of catheterization was 88% (23/26) in the
      experimental group, and 40% (4/10) in the control group. VX2 hepatomas appeared
      as hypointense or isointense nodules on multi-slice spiral CT, and hepatic artery
      angiography showed that VX2 hepatomas had homogeneous or nodular tumor staining.
      CONCLUSION: The modified hepatic artery catheterization using microsurgical
      technique has higher success rate than catheterization with 3F micro-catheter by
      Seldinger technique, and significantly decreases X-ray exposure for the staff
      undertaking the operations.

PMID- 18819893
TI  - [Monocyte human leukocyte antigen-DR expression in elderly patients with sepsis].
AB  - OBJECTIVE: To investigate the changes of human leukocyte antigen DR (HLA-DR)
      expression in the monocytes of elderly patients with sepsis. METHODS: A total of
      213 elderly patients were divided into 4 groups according to the criteria defined
      by the American College of Chest Physicians/ Society of Critical Care Medicine
      (ACCP/SCCM), namely the non-sepsis group (group A), sepsis group (group B),
      severe sepsis group (group C) and septic shock group (group D). Another 60
      healthy subjects were recruited as the control group. HLA-DR expression in the
      monocytes from each subject was determined by flow cytometry, and the HLA-DR
      levels were compared between the groups. RESULTS: Compared with that of the
      healthy control, HLA-DR expression was significantly increased in group A and
      lowered in group D. No significant differences were found between the control
      group and groups B and C. HLA-DR expression was significantly different between
      groups A, B, C, and D (P<0.01), increasing in the order of group D (32.74
      /+13.4)%, group C (61.9-/+14.29)%, group B (69.99-/+12.8)%, and group A (85.06
      /+15.37)%. CONCLUSIONS: Although with multiple organ diseases and repeated or
      long-term hospitalization, the non-septic elderly patients do not show lowered
      expression of HLA-DR. In the elderly patients with sepsis and severe sepsis, HLA
      DR expression is not a sensitive index, but obviously lowered HLA-DR expression
      may serve as a specific indicator in elderly patients with septic shock.

PMID- 18819894
TI  - [Therapeutic effects of imatinib on chronic myeloid leukemia in different phases
      and the factors affecting the effects].
AB  - OBJECTIVE: To evaluate the therapeutic effect of imatinib on chronic myeloid
      leukemia (CML) in different phases and analyze the factors that may affect the
      effects. METHODS: Eighty-five patients with CML in chronic phase, 24 in
      accelerated phase and 19 in blastic phase patients were treated with imitinib.
      The hematologic response, cytogenetic response, molecular response, overall
      survival (OS), progression-free survival (PFS) and adverse events were analyzed
      in these groups. RESULTS: The rates of complete hematologic response (CHR),
      complete cytogenetic response (CCyR) and complete molecular response (CMoR) of
      the patients in chronic phase were 100%, 82.4% and 21.2%, respectively, and the 5
      year OS and PFS of these patients were 92.1% and 84.7%. All these rates were
      significantly higher than those in patients in accelerated and blastic phases
      (P<0.0001). The CCyR, CMoR, 5-year OS and PFS in the 42 newly diagnosed patients
      in chronic phase were 92.9%, 26.3%, 100% and 95.2%, respectively, all
      significantly higher than those in patients with interferon therapy failure
      (P<0.001). Severe leukocytopenia and thrombocytopenia occurred at greater
      frequencey in AP and BP patients than in chronic phase patients (P<0.0001). Non
      hematologic toxicity was rarer and milder in patients in chronic phase.
      Multivariate analysis showed that interferon therapy prior to imitinib treatment
      and prolonged drug cessation were the independent factors that affected the
      achievement of cytogenetic response and PFS. CONCLUSION: Early imitinib therapy
      can be effective and safe, and should be used as the first line drug for CML.

PMID- 18819895
TI  - [Analysis of circulating DNA level in the plasma of cervical cancer patients].
AB  - OBJECTIVE: To determine the plasma DNA level and investigate its
      clinicopathological significance in women with cervical cancers. METHODS: Blood
      samples were collected from 42 cervical cancer patients, 20 patients with
      cervical intraepithelial neoplasia grade III (CINIII) and 20 healthy women. The
      plasma DNA was extracted using a commercial kit and detected by a
      fluorescentmeter. RESULTS: The mean plasma DNA level in stage I cervical cancer
      patients was 12.78-/+5.58 ng/ml, significantly higher than that in CINIII
      patients (8.10-/+3.06 ng/ml) and normal controls (7.60-/+3.87 ng/ml) (P=0.001).
      The mean DNA level in stage II-III patients was 17.99-/+7.81 ng/ml, significantly
      higher than that in stage I patients (P=0.02). No significant difference was
      found in plasma DNA level between CINIII patients and the normal controls
      (P>0.05). When the cut-off for diagnosis of cervical cancer was 15.70 ng/ml, the
      sensitivity, specificity, positive predictive value and negative predictive value
      were 38.10%, 92.50%, 84.21% and 58.73%, respectively. CONCLUSION: Plasma DNA
      level is closely related with malignant transformation and development of
      cervical cancer, and may become a useful means for differential diagnosis of
      cervical cancer.

PMID- 18819896
TI  - [Time course change in the high mobility group box-1 after myocardial infarction
      in rats].
AB  - OBJECTIVE: To investigate the time course change in myocardial high mobility
      group box-1 (HMGB1) after myocardial infarction in rats. METHODS: Myocardial
      infarction (MI) was induced in SD rats by ligation of the anterior descending
      coronary artery. At 1, 2, 4, and 8 weeks after MI, the cardiac function of the
      rats was examined, and the expressions of HMGB1 at mRNA and protein levels in the
      myocardium were detected using real-time RT-PCR and Western blotting,
      respectively. RESULTS: Cardiac function test confirmed that the MI model was
      successfully induced. The expression of HMGB1 mRNA was increased in early stage
      (1 week) after MI, while significantly down-regulated in later stage (4-8 weeks
      after MI). HMGB1 protein showed a similar biphasic pattern of changes, and was up
      regulated early (1-2 weeks) after MI (P<0.05) and decreased markedly (P<0.01) at
      8 weeks. CONCLUSIONS: As an inflammatory regulator, HMGB1 can modulate
      inflammatory response early time after MI and functions later as a
      transcriptional modulator, thus contributing to the myocardial repair after MI.
      Interventions targeting HMGB1 in different stages after MI may prove helpful in
      reducing the complications, improving the prognosis and promoting long-term
      survival.

PMID- 18819897
TI  - [Effect of dexamethasone on the expression of aquaporin-5 in the lungs of mice
      with acute allergic asthma].
AB  - OBJECTIVE: To detect the expression of lung aquaporin 5 (AQP5) in mice with acute
      allergic asthma and the effect of dexamethasone (DEX) treatment on AQP5
      expression, and investigate the role of AOP5 in asthma pathogenesis. METHODS:
      Mouse models of acute allergic asthma were randomly divided into acute asthma
      group, normal control group and DEX treatment group. The total number of white
      blood cells, the subpopulations, and the levels of IL-5 and IFN-gamma were
      detected in the bronchoalveolar larvage fluid (BALF). The lung tissue AQP5 mRNA
      expression was detected by RT-PCR, and AQP5 distribution by immunohistochemical
      method. RESULTS: In asthma group, the total white blood cells, eosinophils and IL
      5 levels were all significantly higher (P<0.01) and IFN-gamma levels lower than
      those of the control group (P<0.01). After DEX treatment, the levels underwent a
      significant reverse change (P<0.05, P<0.01, P<0.01, and P<0.01, respectively).
      AQP5 mRNA expression in the asthma group was significantly higher than that in
      the control group (P<0.01), and was significantly lowered with DEX treatment
      (P<0.01). Extensive inflammatory changes, mucus hypersecrection, several edema
      and inflammatory cell infitration around the blood vessels were observed in the
      lung tissue of the mice in the asthma group. The morphological changes of the
      treatment group were significantly ameliorated. AQP5 protein was detected in the
      type I alveolar epithelial cells, the airway columnar epithelial cells and the
      apical membranes of the submucosal gland acinar cells in the control group.
      Stronger AQP5 protein expression was found in the asthma group. CONCLUSION: AQP5
      is over-expressed in mice with acute asthma which is possibly associated with
      mucus hypersecrection. DEX can inhibit AQP5 expression and ameliorate allergic
      airway inflammation, edema and mucus hypersecrection.

PMID- 18819898
TI  - [Optimization of the supercritical fluid extraction process of Tuirezhitongsan].
AB  - OBJECTIVE: To optimize the extraction process of Tuirezhitongsan and extract the
      pharmacodynamically active fractions. METHODS: Orthogonal test methods and
      supercritical-CO(2) fluid extraction (SFE-CO(2)) were used for the extraction,
      and the the pharmacodynamically active fractions were screened with analgesic
      experiments. RESULTS: The optimal extraction of the active fractions was achieved
      with the extraction pressure at 25 MPa, extraction temperature at 45 degrees
      celsius, resolution pressure at 6.7 MPa, and resolution temperature at 50 degrees
      celsius. CONCLUSION: SFE- CO(2) is rapid, efficient, and energy-saving in the
      extraction of the active fractions in Tuirezhotongsan, and provides a mew method
      for extraction of traditional Chinese medicine.

PMID- 18819899
TI  - [Relationship of interleukin-1beta, tumor necrosis factors-beta and interleukin
      10 gene polymorphisms with serum lipoprotein level in Chinese Han population in
      Guangdong Province].
AB  - OBJECTIVE: To investigate the association of IL-1beta+3953, TNFbeta+252 and IL-10
      592 polymorphisms with serum lipoprotein levels in Chinese Han population in
      Guangdong Province. METHODS: A total of 428 individuals of Han nationality from
      Guangdong Province were enrolled in this study. The genotypes of IL-1beta+3953,
      TNFbeta+252 and IL-10-592 sites were detected using polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP). The serum concentrations of
      total cholesterol (TC), TG, low-density lipoprotein (LDL), high-density
      lipoprotein (HDL), and very low density lipoprotein (VLDL) were determined using
      an automatic biochemistry analyzer. RESULTS: The concentrations of TC and LDL in
      individuals of TNFbeta+252GA genotype was significantly higher than that in
      TNFbeta+252AA genotype (t=-2.406, P=0.017; t=-2.516, P=0.012). The concentration
      of LDL in IL-10+3953CT genotype was significantly higher than that in IL
      10+3953CC genotype (2.743-/+0.723 vs 2.502-/+0.699 mmol/L, t=-2.639, P=0.009). No
      significant differences were found in TG, TC, HDL, LDL and VLDL between the 3
      genotypes (P>0.05). CONCLUSION: The polymorphisms of proinflammatory cytokines
      are related to the serum lipoprotein level in these subjects. The T allele in IL
      1beta+3953 and the G allele in TNFbeta+252 are positively correlated to
      dyslipidemia.

PMID- 18819900
TI  - [Coadministration of sorafenib and cisplatin inhibits proliferation of
      hepatocellular carcinoma HepG2 cells in vitro].
AB  - OBJECTIVE: To investigate the inhibitory effect of sorafenib in combination with
      cisplatin (DDP) on the proliferation of hepatocellular carcinoma cells and
      explore the molecular mechanisms. METHODS: The inhibitory effect of sorafenib and
      DDP treatment on HepG2 cell proliferation in vitro was assessed by MTT assay. The
      cell cycle changes and the apoptotic rate of the treated cells were detected by
      flow cytometry, and the expressions of ERK and pERK examined using Western
      blotting. RESULTS: Sorafenib and DDP alone both significantly inhibited the
      proliferation of HepG2 cells, showing a synergistic effect of their actions in
      combined use (P<0.05). Sorafenib and DDP alone caused cell cycle arrest at G(1)
      and G(2) phases, respectively. Combined use of the two drugs resulted in
      significant reduction of the S-phase cell percentage and cell cycle arrest at
      G(1) and G(2) phases. The coadministration of the drugs significantly increased
      the apoptosis rate of the cells as compared with the that of the cells with
      sorafenib or DDP treatment alone (P<0.05). Sorafenib and DDP, used alone or in
      combination, did not produce obvious effect on ERK expression. Sorafenib
      treatment for 24 h reduced pERK expression in the HepG2 cells, and the effect was
      enhanced by combined treatment with sorafenib and DDP. CONCLUSIONS: Sorafenib and
      DDP show a synergistic effect in inhibiting the proliferation and inducing
      apoptosis of HepG2 cells. The mechanisms of this synergistic effect can be
      closely related to the double blockage of the cell cycle and Raf/MEK/ERK pathway
      inhibition.

PMID- 18819901
TI  - [Local mild hypothermia therapy for neurogenic pulmonary edema].
AB  - OBJECTIVE: To investigate the changes in stress hormones in neurogenic pulmonary
      edema (NPE) and explore the clinical value of mild hypothermia therapy for
      treatment of NPE. METHODS: Fifty-two patients with cerebral hemorrhage patients
      and concomitant NPE were randomly divided into two groups for local mild
      hypothermia therapy (23 cases, LMH group) or routine treatment (29 cases, RT
      group). In the former group, local mild hypothermia therapy was applied in
      addition to the routine treatment. The changes of serum corticotrophin-releasing
      hormone (CRH), adrenocorticotropic hormone (ACTH), corticosteroid (Cor), arginine
      vasopressin (AVP) and blood sugar were observed before and 7 days after the
      treatment, and compared with those of 58 NPE-free patients with cerebral
      hemorrhage and 40 healthy individuals. RESULTS: Serum CRH, ACTH, Cor, and AVP
      levels and blood sugar in NPE patients and the NPE-free patients were all
      significantly higher than those in the healthy individuals (P<0.01), and the
      levels were significantly higher in NPE patients than in the NPE-free patients
      (P<0.05). In the NPE patients, the mortality rate and NIHSS score were
      significantly lower in RT group (P<0.01); after 7 days of treatment, both LMH and
      RT groups showed significant reduction in serum CRH, ACTH, Cor, and AVP levels
      (P<0.05), and the reduction was more conspicuous in LMH group (P<0.05).
      CONCLUSION: The occurrence of NPE is closely associated with stress reactions,
      which might be the basis of NPE. Local mild hypothermia therapy improves of the
      quality of life of NPE patients and also decreases the mortality of NPE possibly
      by inhibiting the secretion of stress hormones and stabilizing the hypothalamic
      pituitary-adrenal axis.

PMID- 18819902
TI  - [Value of multi-slice spiral CT with three-dimensional reconstruction in the
      diagnosis of neoplastic lesions in the jawbones].
AB  - OBJECTIVE: To assess the value of multi-slice spiral CT (MSCT) with three
      dimensional (3D) reconstruction in the diagnosis of neoplastic lesions in the
      jawbones. METHODS: Thirty-three patients with neoplastic lesions of the jawbones
      underwent MSCT scanning with 3D reconstruction. Of these patients, 14 had
      ameloblastoma, 8 had hemangioma, 3 had osteosarcoma, 3 had ossifying fibroma, 2
      had chondrosarcoma, 2 had fibrosarcoma, and 1 had odontogenic myxoma.
      Preoperative MSCT scanning was performed with the slice thickness of 2 mm, and 3D
      reconstruction of the images was conducted by means of multi-planar
      reconstruction (MPR), curved-planar reformation (CRP), and 3D volume rendering
      technique (VRT). The results were compared with those observed during the
      operations. RESULTS: In the 33 cases, the neoplastic lesions of the jawbones were
      displayed by 2D or 3D imaging and confirmed by intraoperative findings. Two
      dimensional imaging allowed better observation than 3D imaging of the deep
      structures, whereas 3D imaging was superior in visualizing the morphological
      changes of the compromised bones and the spatial relationship between the tumors
      and surrounding structures. Two-dimensional imaging and MPR were excellent in
      revealing the internal structures and pathological changes of tumors, having also
      better performance in showing the tumors involving the soft tissues. Benign
      tumors were most visualized as bone expansion changes with well defined ovoid or
      lobulated borderlines, and malignant ones often resulted in adjacent bony
      destruction and soft tissue masses. CONCLUSION: MSCT examination is useful in
      defining the scope of tumor involvement and bony changes to help in the definite
      diagnosis, differential diagnosis and choice of clinical treatment. Two
      dimensional imaging, MPR, VRT and CRP have their respective advantages and
      limitations in showing jawbone tumor, and their combination can be of great
      clinical value.

PMID- 18819903
TI  - [Effect of the sera of rabbits fed with Tongxinluo on MMP-9 and TIMP-1 expression
      and secretion in U937 monocyte-derived macrophages].
AB  - OBJECTIVE: To investigate the effect of the sera of rabbits fed with Tongxinluo
      on the expression and secretion of matrix metalloproteinase-9 (MMP-9) and tissue
      inhibitor of metalloproteinase-1 (TIMP-1) in U937 monocyte-derived macrophages.
      METHODS: Atherosclerosis was induced in rabbits by high-cholesterol feeding, and
      the serum was obtained from the rabbits after administration of the aqueous
      solution of Tongxinluo or simvastatin by gavage. U937 monocyte-derived
      macrophages were incubated with the sera at different concentrations for 24
      hours, and the changes in MMP-9 and TIMP-1 gene expression and secretion were
      detected by RT-PCR and enzyme-linked immunosorbent assay, respectively. RESULTS:
      The serum of rabbits fed with Tongxinluo concentration-dependently inhibited the
      expression and secretion of MMP-9 in U937 macrophages, but did not affect TIMP-1
      expression or secretion. CONCLUSION: Tongxinluo may stabilize the atherosclerotic
      plaques by inhibiting the expression and secretion of MMP-9.

PMID- 18819904
TI  - [Efficacy and toxicity of trastuzumab combined vinorelbine in 21 patients with
      HER2 overexpressing metastatic breast cancer].
AB  - OBJECTIVE: To evaluate the efficacy and toxicity in patients with HER2
      overexpressing metastatic breast cancer. METHODS: Twenty-one patients with HER2
      overexpressing metastatic breast cancer entered into the study. Trastuzumab (8
      mg/kg day 1, then 6 mg/kg every 21 days or 4 mg/kg, then 2 mg/kg every week) and
      vinorelbine (25 mg/m(2)) was given on days 1 and 8 every 21 days. RESULTS:
      Overall 56 cycles were given to the 21 patients enrolled into the study (mean 2,
      range 1-6). All can be evaluated. The response rate was 33.33% (7/21), one
      patient achieved complete response (CR), six patients achieved partial response
      (PR), four patients achieved stable disease (SD), ten patients achieved
      progressive disease (PD)]. The median time to progression was 3.5 months. One
      year overall survival was 33%. The major toxicity was myelosuppression and
      peripheral neuritis. A few patients were observed with fever and lower grade
      cardiac failure. CONCLUSION: The combination of trastuzumab and vinorelbine is an
      effective and well tolerated therapy in patients with pretreated metastatic
      breast cancer.

PMID- 18819905
TI  - [Establishment of a rabbit model bearing transplanted endometrial carcinoma and
      magnetic resonance imaging features of the metastatic lymph nodes].
AB  - OBJECTIVE: To establish a rabbit model bearing endometrial carcinoma and observe
      the magnetic resonance imaging (MRI) features of the metastatic lymph nodes.
      METHODS: VX(2) tumor grafts were orthotopically embedded into the endometrium of
      the rabbits. Three weeks after the implantation, the tumor and the metastatic
      retroperitoneal lymph nodes were examined with MRI, and the signal intensities
      and the size of the lymph nodes were compared with those in normal rabbits.
      RESULTS: Orthotopic tumor growth was observed in all the rabbits. Tumor
      infiltration of the serosa and retroperitoneal lymph node metastasis occurred 3
      weeks after tumor implantation. MRI demonstrated obviously lymph node enlargement
      in the tumor-bearing rabbits as compared with those of normal rabbits, while the
      signal intensity of the lymph nodes were comparable between them. CONCLUSION: The
      endometrial carcinoma in this rabbit model well simulate the metastatic behavior
      of human endometrial carcinoma, and may serve as a good model for testing the
      efficacy of the contrast agents for MRI of the lymph nodes.

PMID- 18819906
TI  - [Mifepristone modulates glucosylceramide synthase expression and reverse
      multidrug resistance in ovarian cancer cells].
AB  - OBJECTIVE: To evaluate the effect of mifepristone in reversing multidrug
      resistance(MDR) and modulating glucosylceramide synthase (GCS) mRNA expression in
      human ovarian cancer COC(1)/DDP cells. METHODS: MDR cell line COC(1)/DDP was
      treated with mifepristone at different concentrations. The alterations in the
      chemosensitivity of the cells to cisplatin (DDP) were evaluated by MTT assay. GCS
      mRNA expression in COC(1)/DDP cells were detected using RT-PCR before and after
      mifepristone treatment. RESULTS: The expression level of GCS mRNA was 1.1792 in
      COC(1)/DDP cells, significantly higher than that in COC(1) cells (0.2836).
      Mifepristone at 1.25-10 micromol/L increased the sensitivity of COC(1)/DDP cells
      to cisplatin, and inhibited GCS expression at the mRNA level, showing
      concentration-dependent modulation of MDR and gene expression in the cells.
      CONCLUSION: Mifepristone can dose-dependently lower cisplatin resistance of
      COC(1)/DDP cells, the mechanism of which involves inhibition of GCS expression.

PMID- 18819907
TI  - [Clinical value of the model for end-stage liver disease score in predicting the
      prognosis of liver transplantation in patients with end-stage liver disease].
AB  - OBJECTIVE: To assess the value of the model for end-stage liver disease (MELD) in
      predicting the early-stage outcome of liver transplantation in patients with end
      stage liver disease. METHODS: The MELD scores of 87 liver transplantation
      recipients with end-stage liver disease were calculated, and their early-stage
      complications and mortality were analyzed. RESULTS: The incidence of severe
      complications was 20.7%; in these recipients, with the 28-day and 3-month
      survival rates of 89.7%; and 88.5%;, respectively. The mean MELD scores showed
      significant differences between the complication-free group and survival group
      (14.6 vs 12.9, P<0.05), and also between the complication group and death group
      (21.6 vs 29.4, P<0.05). Compared to patients with MELD no greater than 15,
      patients with MELD between 16 and 24 showed significantly increased complication
      rate but had comparable survival rate (P>0.05); but in patients with MELD no less
      than 25, the survival rate was significantly decreased with also increased
      complication rate. CONCLUSIONS: A higher MELD score before liver transplantation
      is associated with greater likeliness of early-stage complication rate and
      mortality. High MELD score (over 25) can be a useful index in predicting severe
      complications and death in patients undergoing liver transplantation.

PMID- 18819908
TI  - [Comparison study on diagnostic and prognostic value of N-terminal probrain
      natriuretic peptide and atrium natriuretic peptide in chronic congestive heart
      failure].
AB  - OBJECTIVE: To investigate the diagnostic and prognostic value of N-terminal
      probrain natriuretic peptide(NT-proBNP)and atrium natriuretic peptide(ANP)in
      chronic congestive heart failure. METHODS: One hundred and eighteen coronary
      heart disease patients were enrolled in the study. Among them 78 patients were
      accompanied by heart failure and 40 with no heart failure. Plasma NT-proBNP was
      determined with Elecsys Chemiluminescence Immunoassay method, and plasma ANP was
      determined with radioimmunoassay method.The results were compared with those of
      40 healthy individuals. All patients were followed up accordingly. RESULTS:
      Compared with patients with no heart failure and healthy individuals, the
      patients with heart failure had a higher plasma NT-proBNP and ANP
      contents(P<0.05). Cardiac function grade IV patients had a significantly higher
      plasma NT-proBNP than cardiac function grade II and III patients, and their
      plasma ANP level was significanthy higher than that of cardiac function grade III
      patients, but there was no significantly difference in ANP content between
      cardiac function grade IV and II.The diagnostic sensitivity of NT-proBNP and ANP
      was 91.25% and 73.46%, respectively. The diagnostic specificity of NT-proBNP and
      ANP was 90.25%, 80.33%, respectively. In the heart failure group, it was found
      that there was no significant difference in the plasma NT-proBNP and ANP between
      the deaths and surviving patients. CONCLUSION: The diagnostic value of NT-proBNP
      in chronic heart failure is higher than that of ANP. According to our follow- up
      result, the plasma NT-proBNP and ANP can not be relied up on to predict short 
      term cardiogenic death in heart failure.

PMID- 18819909
TI  - The COOH-terminal domain of the JIL-1 histone H3S10 kinase interacts with histone
      H3 and is required for correct targeting to chromatin.
AB  - The JIL-1 histone H3S10 kinase in Drosophila localizes specifically to
      euchromatic interband regions of polytene chromosomes and is enriched 2-fold on
      the male X chromosome. JIL-1 can be divided into four main domains including an
      NH(2)-terminal domain, two separate kinase domains, and a COOH-terminal domain.
      Our results demonstrate that the COOH-terminal domain of JIL-1 is necessary and
      sufficient for correct chromosome targeting to autosomes but that both COOH- and
      NH(2)-terminal sequences are necessary for enrichment on the male X chromosome.
      We furthermore show that a small 53-amino acid region within the COOH-terminal
      domain can interact with the tail region of histone H3, suggesting that this
      interaction is necessary for the correct chromatin targeting of the JIL-1 kinase.
      Interestingly, our data indicate that the COOH-terminal domain alone is
      sufficient to rescue JIL-1 null mutant polytene chromosome defects including
      those of the male X chromosome. Nonetheless, we also found that a truncated JIL-1
      protein which was without the COOH-terminal domain but retained histone H3S10
      kinase activity was able to rescue autosome as well as partially rescue male X
      polytene chromosome morphology. Taken together these findings indicate that JIL-1
      may participate in regulating chromatin structure by multiple and partially
      redundant mechanisms.

PMID- 18819910
TI  - Ethylmalonyl-CoA mutase from Rhodobacter sphaeroides defines a new subclade of
      coenzyme B12-dependent acyl-CoA mutases.
AB  - Coenzyme B(12)-dependent mutases are radical enzymes that catalyze reversible
      carbon skeleton rearrangement reactions. Here we describe Rhodobacter sphaeroides
      ethylmalonyl-CoA mutase (Ecm), a novel member of the family of coenzyme B(12)
      dependent acyl-CoA mutases, that operates in the recently discovered ethylmalonyl
      CoA pathway for acetate assimilation. Ecm is involved in the central reaction
      sequence of this novel pathway and catalyzes the transformation of ethylmalonyl
      CoA to methylsuccinyl-CoA in combination with a second enzyme that was further
      identified as promiscuous ethylmalonyl-CoA/methylmalonyl-CoA epimerase. In
      contrast to the epimerase, Ecm is highly specific for its substrate, ethylmalonyl
      CoA, and accepts methylmalonyl-CoA only at 0.2% relative activity. Sequence
      analysis revealed that Ecm is distinct from (2R)-methylmalonyl-CoA mutase as well
      as isobutyryl-CoA mutase and defines a new subfamily of coenzyme B(12)-dependent
      acyl-CoA mutases. In combination with molecular modeling, two signature sequences
      were identified that presumably contribute to the substrate specificity of these
      enzymes.

PMID- 18819911
TI  - On the mechanism of pore formation by melittin.
AB  - The mechanism of pore formation of lytic peptides, such as melittin from bee
      venom, is thought to involve binding to the membrane surface, followed by
      insertion at threshold levels of bound peptide. We show that in membranes
      composed of zwitterionic lipids, i.e. phosphatidylcholine, melittin not only
      forms pores but also inhibits pore formation. We propose that these two modes of
      action are the result of two competing reactions: direct insertion into the
      membrane and binding parallel to the membrane surface. The direct insertion of
      melittin leads to pore formation, whereas the parallel conformation is inactive
      and prevents other melittin molecules from inserting, hence preventing pore
      formation.

PMID- 18819912
TI  - Role of HRB in clathrin-dependent endocytosis.
AB  - Human immunodeficiency virus Rev-binding protein (HRB), also called human Rev
      interacting protein (hRIP) or Rev/Rex activation domain binding (RAB) is a
      partner of the tyrosine kinase substrate EPS15, and it has been recovered in the
      AP-2 interactome. EPS15 and AP-2 are involved in endocytosis, but the function of
      HRB in this process is still unknown. Here we identified HRB as a partner of the
      vesicular SNARE tetanus neurotoxin-insensitive vesicle-associated membrane
      protein (TI-VAMP, also called VAMP7) in yeast two-hybrid screens and using
      biochemical assays. In HeLa cells, HRB localized both in the nucleus and in the
      cytoplasm. In the cytoplasm, HRB colocalized with clathrin-, AP-2-, EPS15-, and
      transferrin receptor-containing vesicles. We did not see significant
      colocalization between HRB and TI-VAMP in HeLa cells, and we saw partial
      colocalization with green fluorescent protein-TI-VAMP in stably expressing Madin
      Darby canine kidney cells. Nevertheless using a pHLuorin-tagged TI-VAMP
      construct, we found that HRB and TI-VAMP colocalize close to the plasma membrane
      after 5 min of anti-green fluorescent protein antibody uptake. These results
      suggest that TI-VAMP and HRB may interact only during the early stages of
      endocytosis. Furthermore uptake experiments followed by fluorescence-activated
      cell sorting showed that the endocytosis of fluorescent transferrin and pHLuorin
      TI-VAMP is strongly reduced in HRB knockdown cells. Altogether these results
      suggest that HRB is involved in clathrin-dependent endocytosis and recruits TI
      VAMP in this process.

PMID- 18819913
TI  - Dentin matrix protein-1 isoforms promote differential cell attachment and
      migration.
AB  - Dentin matrix protein-1 (DMP1), bone sialoprotein (BSP), and osteopontin (OPN)
      are three SIBLINGs (small integrin-binding ligand, N-linked glycoproteins) co
      expressed/secreted by skeletal and active ductal epithelial cells. Although
      etiological mechanisms remain unclear, DMP1 is the only one of these three genes
      currently known to have mutations resulting in human disease, and yet it remains
      the least studied. All three contain the highly conserved integrin-binding
      tripeptide, RGD, and experiments comparing the cell attachment and haptotactic
      migration-enhancing properties of DMP1 to BSP and OPN were performed using human
      skeletal (MG63 and primary dental pulp cells) and salivary gland (HSG) cells.
      Mutation of any SIBLING's RGD destroyed all attachment and migration activity.
      Using its alphaVbeta5 integrin, HSG cells attached to BSP but not to DMP1 or OPN.
      However, HSG cells could not migrate onto BSP in a modified Boyden chamber assay.
      Expression of alphaVbeta3 integrin enhanced HSG attachment to DMP1 and OPN and
      promoted haptotactic migration onto all three proteins. Interchanging the first
      four coding exons or the conserved amino acids adjacent to the RGD of DMP1 with
      corresponding sequences of BSP did not enhance the ability of DMP1 to bind
      alphaVbeta5. For alphaVbeta3-expressing cells, intact DMP1, its BMP1-cleaved C
      terminal fragment, and exon six lacking all post-translational modifications
      worked equally well but the proteoglycan isoform of DMP1 had greatly reduced
      ability for cell attachment and migration. The sequence specificity of the
      proposed BMP1-cleavage site of DMP1 was verified by mutation analysis. Direct
      comparison of the three proteins showed that cells discriminate among these
      SIBLINGs and among DMP1 isoforms.

PMID- 18819914
TI  - Nedd4 family-interacting protein 1 (Ndfip1) is required for the exosomal
      secretion of Nedd4 family proteins.
AB  - The ability to remove unwanted proteins is an important cellular feature.
      Classically, this involves the enzymatic addition of ubiquitin moieties followed
      by degradation in the proteasome. Nedd4 proteins are ubiquitin ligases important
      not only for protein degradation, but also for protein trafficking. Nedd4
      proteins can bind to target proteins either by themselves or through adaptor
      protein Ndfip1 (Nedd4 family-interacting protein 1). An alternative mechanism for
      protein removal and trafficking is provided by exosomes, which are small vesicles
      (50-90-nm diameter) originating from late endosomes and multivesicular bodies
      (MVBs). Exosomes provide a rapid means of shedding obsolete proteins and also for
      cell to cell communication. In the present work, we show that Ndfip1 is
      detectable in exosomes secreted from transfected cells and also from primary
      neurons. Compared with control, Ndfip1 increases exosome secretion from
      transfected cells. Furthermore, while Nedd4, Nedd4-2, and Itch are normally
      absent from exosomes, expression of Ndfip1 results in recruitment of all three
      Nedd4 proteins into exosomes. Together, these results suggest that Ndfip1 is
      important for protein trafficking via exosomes, and provides a mechanism for
      cargoing passenger proteins such as Nedd4 family proteins. Given the positive
      roles of Ndfip1/Nedd4 in improving neuronal survival during brain injury, it is
      possible that exosome secretion provides a novel route for rapid sequestration
      and removal of proteins during stress.

PMID- 18819915
TI  - Sec61p is required for ERAD-L: genetic dissection of the translocation and ERAD-L
      functions of Sec61P using novel derivatives of CPY.
AB  - Misfolded proteins in the endoplasmic reticulum (ER) are exported to the cytosol
      for degradation by the proteasome in a process known as ER-associated degradation
      (ERAD). CPY* is a well characterized ERAD substrate whose degradation is
      dependent upon the Hrd1 complex. However, although the functions of some of the
      components of this complex are known, the nature of the protein dislocation
      channel remains obscure. Sec61p has been suggested as an obvious candidate
      because of its role as a protein-conducting channel through which polypeptides
      are initially translocated into the ER. However, it has not yet been possible to
      functionally dissect any role for Sec61p in dislocation from its essential
      function in translocation. By changing the translocation properties of a series
      of novel ERAD substrates, we are able to separate these two events and find that
      functional Sec61p is essential for the ERAD-L pathway.

PMID- 18819917
TI  - Sulfated polysaccharides promote the assembly of amyloid beta(1-42) peptide into
      stable fibrils of reduced cytotoxicity.
AB  - The histopathological hallmarks of Alzheimer disease are the self-aggregation of
      the amyloid beta peptide (Abeta) in extracellular amyloid fibrils and the
      formation of intraneuronal Tau filaments, but a convincing mechanism connecting
      both processes has yet to be provided. Here we show that the endogenous
      polysaccharide chondroitin sulfate B (CSB) promotes the formation of fibrillar
      structures of the 42-residue fragment, Abeta(1-42). Atomic force microscopy
      visualization, thioflavin T fluorescence, CD measurements, and cell viability
      assays indicate that CSB-induced fibrils are highly stable entities with abundant
      beta-sheet structure that have little toxicity for neuroblastoma cells. We
      propose a wedged cylinder model for Abeta(1-42) fibrils that is consistent with
      the majority of available data, it is an energetically favorable assembly that
      minimizes the exposure of hydrophobic areas, and it explains why fibrils do not
      grow in thickness. Fluorescence measurements of the effect of different Abeta(1
      42) species on Ca(2+) homeostasis show that weakly structured nodular fibrils,
      but not CSB-induced smooth fibrils, trigger a rise in cytosolic Ca(2+) that
      depends on the presence of both extracellular and intracellular stocks. In vitro
      assays indicate that such transient, local Ca(2+) increases can have a direct
      effect in promoting the formation of Tau filaments similar to those isolated from
      Alzheimer disease brains.

PMID- 18819916
TI  - Genetic toggling of alkaline phosphatase folding reveals signal peptides for all
      major modes of transport across the inner membrane of bacteria.
AB  - Prediction of export pathway specificity in prokaryotes is a challenging endeavor
      due to the similar overall architecture of N-terminal signal peptides for the Sec
      , SRP- (signal recognition particle), and Tat (twin arginine translocation)
      dependent pathways. Thus, we sought to create a facile experimental strategy for
      unbiased discovery of pathway specificity conferred by N-terminal signals. Using
      a limited collection of Escherichia coli strains that allow protein oxidation in
      the cytoplasm or, conversely, disable protein oxidation in the periplasm, we were
      able to discriminate the specific mode of export for PhoA (alkaline phosphatase)
      fusions to signal peptides for all of the major modes of transport across the
      inner membrane (Sec, SRP, or Tat). Based on these findings, we developed a mini
      Tn5 phoA approach to isolate pathway-specific export signals from libraries of
      random fusions between exported proteins and the phoA gene. Interestingly, we
      observed that reduced PhoA was exported in a Tat-independent manner when targeted
      for Tat export in the absence of the essential translocon component TatC. This
      suggests that initial docking to TatC serves as a key specificity determinant for
      Tat-specific routing of PhoA, and in its absence, substrates can be rerouted to
      the Sec pathway, provided they remain compatible with the Sec export mechanism.
      Finally, the utility of our approach was demonstrated by experimental
      verification that four secreted proteins from Mycobacterium tuberculosis carrying
      putative Tat signals are bona fide Tat substrates and thus represent potential
      Tat-dependent virulence factors in this important human pathogen.

PMID- 18819918
TI  - Regulation of pluripotency and reprogramming by transcription factors.
AB  - Living organisms, from virus to human, rely on the transcription machinery to
      express specific parts of their genomes to execute critical biological functions
      during their life cycle by responding to environmental or developmental signals.
      Thus, transcription constitutes a critical step in regulating biological
      processes, and transcription factors have been considered as master switches for
      cell fate determination. Stem cell biology has benefited from rapid advances in
      recent years, largely because of the characterization of several transcription
      factors as master regulators of stem cell pluripotency. The same factors, viz.
      Oct4, Sox2, Nanog, Klf4, and Myc, have been shown to possess the magic power to
      reprogram somatic cells into pluripotent ones, a remarkable achievement with both
      practical and theoretical implications. This minireview summarizes recent
      advances in pluripotency and reprogramming by focusing on key transcription
      factors and the likely mechanisms.

PMID- 18819919
TI  - Post-transcriptional modulation of iron homeostasis during p53-dependent growth
      arrest.
AB  - Iron plays an essential role in cell proliferation and is a required cofactor for
      a number of critical cellular enzymes. In this report we investigate changes in
      proteins of iron metabolism during p53-mediated replicative arrest. Following the
      induction of p53 in H1299 lung cancer cells containing a doxycycline-inducible
      p53, an increase in both H and L subunits of ferritin protein was observed. To
      determine the mechanism of this effect, we investigated the ability of p53 to
      regulate ferritin. Real time reverse transcription-PCR demonstrated no difference
      in levels of ferritin H mRNA in the presence and absence of p53. Because these
      results suggested that transcriptional mechanisms were not responsible for the
      p53-dependent increase in ferritin, we tested whether a post-transcriptional
      mechanism was involved. RNA bandshift assays revealed that induction of p53
      decreased iron regulatory protein binding. Consistent with this observation,
      Western blot analysis revealed a decline in transferrin receptor 1 protein levels
      following induction of p53. Collectively, these results suggest that p53 may
      induce cell cycle arrest not only by well described mechanisms involving the
      induction of cyclin-dependent kinase inhibitors but also by the recruitment of
      pathways that reduce the availability of intracellular iron.

PMID- 18819920
TI  - Oversulfated chondroitin sulfate plays critical roles in the neuronal migration
      in the cerebral cortex.
AB  - Chondroitin sulfate (CS) proteoglycans bind with various proteins through CS
      chains in a CS structure-dependent manner, in which oversulfated structures, such
      as iB (IdoA(2-O-sulfate)alpha1-3GalNAc(4-O-sulfate)), D (GlcA(2-O-sulfate)beta1
      3GalNAc(6-O-sulfate)), and E (GlcAbeta1-3GalNAc(4,6-O-disulfate)) units
      constitute the critical functional module. In this study, we examined the
      expression and function of three CS sulfotransferases in the developing
      neocortex: uronyl 2-O-sulfotransferase (UST), N-acetylgalactosamine 4-sulfate 6-O
      sulfotransferase (4,6-ST) and dermatan 4-O-sulfotransferase-1 (D4-ST), which are
      responsible for the synthesis of oversulfated structures. The CS chains of the
      neocortex of mouse embryos contained significant amounts of D and E units that
      are generated by UST and 4,6-ST, respectively. UST and 4,6-ST mRNAs were
      expressed in the ventricular and subventricular zones, and their expression
      increased during late embryonic development. In utero electroporation experiments
      indicated that knockdown of UST and 4,6-ST resulted in the disturbed migration of
      cortical neurons. The neurons electroporated with the short hairpin RNA
      constructs of UST and 4,6-ST accumulated in the lower intermediate zone and in
      the subventricular zone, showing a multipolar morphology. The cDNA constructs of
      UST and 4,6-ST rescued the defects caused by the RNA interference, and the
      neurons were able to migrate radially. On the other hand, knockdown of D4-ST,
      which is involved in the biosynthesis of the iB unit, caused no migratory
      defects. These results revealed that specific oversulfated structures in CS
      chains play critical roles in the migration of neuronal precursors during
      cortical development.

PMID- 18819921
TI  - Regulation of the Met receptor-tyrosine kinase by the protein-tyrosine
      phosphatase 1B and T-cell phosphatase.
AB  - The non-receptor protein-tyrosine phosphatases (PTPs) 1B and T-cell phosphatase
      (TCPTP) have been implicated as negative regulators of multiple signaling
      pathways including receptor-tyrosine kinases. We have identified PTP1B and TCPTP
      as negative regulators of the hepatocyte growth factor receptor, the Met receptor
      tyrosine kinase. In vivo, loss of PTP1B or TCPTP enhances hepatocyte growth
      factor-mediated phosphorylation of Met. Using substrate trapping mutants of PTP1B
      or TCPTP, we have demonstrated that both phosphatases interact with Met and that
      these interactions require phosphorylation of twin tyrosines (Tyr-1234/1235) in
      the activation loop of the Met kinase domain. Using confocal microscopy, we show
      that trapping mutants of both PTP1B and the endoplasmic reticulum-targeted TCPTP
      isoform, TC48, colocalize with Met and that activation of Met enables the nuclear
      localized isoform of TCPTP, TC45, to exit the nucleus. Using small interfering
      RNA against PTP1B and TCPTP, we demonstrate that phosphorylation of Tyr-1234/1235
      in the activation loop of the Met receptor is elevated in the absence of either
      PTP1B or TCPTP and further elevated upon loss of both phosphatases. This enhanced
      phosphorylation of Met corresponds to enhanced biological activity and cellular
      invasion. Our data demonstrate that PTP1B and TCPTP play distinct and non
      redundant roles in the regulation of the Met receptor-tyrosine kinase.

PMID- 18819922
TI  - Signal regulatory proteins (SIRPS) are secreted presynaptic organizing molecules.
AB  - Formation of chemical synapses requires exchange of organizing signals between
      the synaptic partners. Using synaptic vesicle aggregation in cultured neurons as
      a marker of presynaptic differentiation, we purified candidate presynaptic
      organizers from mouse brain. A major bioactive species was the extracellular
      domain of signal regulatory protein alpha (SIRP-alpha), a transmembrane
      immunoglobulin superfamily member concentrated at synapses. The extracellular
      domain of SIRP-alpha is cleaved and shed in a developmentally regulated manner.
      The presynaptic organizing activity of SIRP-alpha is mediated in part by CD47.
      SIRP-alpha homologues, SIRP-beta and -gamma also have synaptic vesicle clustering
      activity. The effects of SIRP-alpha are distinct from those of another
      presynaptic organizer, FGF22: the two proteins induced vesicle clusters of
      different sizes, differed in their ability to promote neurite branching, and
      acted through different receptors and signaling pathways. SIRP family proteins
      may act together with other organizing molecules to pattern synapses.

PMID- 18819923
TI  - Long term synaptic depression that is associated with GluR1 dephosphorylation but
      not alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor
      internalization.
AB  - Long lasting changes in the strength of synaptic transmission in the hippocampus
      are thought to underlie certain forms of learning and memory. Accordingly, the
      molecular mechanisms that account for these changes are heavily studied.
      Postsynaptically, changes in synaptic strength can occur by altering the amount
      of neurotransmitter receptors at the synapse or by altering the functional
      properties of synaptic receptors. In this study, we examined the biochemical
      changes produced following chemically induced long term depression in acute
      hippocampal CA1 minislices. Using three independent methods, we found that this
      treatment did not lead to an internalization of alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid (AMPA) receptors. Furthermore, when the plasma membrane
      was separated into synaptic membrane-enriched and extrasynaptic membrane-enriched
      fractions, we actually observed a significant increase in the concentration of
      AMPA receptors at the synapse. However, phosphorylation of Ser-845 on the AMPA
      receptor subunit GluR1 was significantly decreased throughout the neuron,
      including in the synaptic membrane-enriched fraction. In addition,
      phosphorylation of Ser-831 on GluR1 was decreased specifically in the synaptic
      membrane-enriched fraction. Phosphorylation of these residues has been
      demonstrated to control AMPA receptor function. From these data, we conclude that
      the decrease in synaptic strength is likely the result of a change in the
      functional properties of AMPA receptors at the synapse and not a decrease in the
      amount of synaptic receptors.

PMID- 18819924
TI  - ErbB4-neuregulin signaling modulates synapse development and dendritic
      arborization through distinct mechanisms.
AB  - Perturbations in neuregulin-1 (NRG1)/ErbB4 function have been associated with
      schizophrenia. Affected patients exhibit altered levels of these proteins and
      display hypofunction of glutamatergic synapses as well as altered neuronal
      circuitry. However, the role of NRG1/ErbB4 in regulating synapse maturation and
      neuronal process formation has not been extensively examined. Here we demonstrate
      that ErbB4 is expressed in inhibitory interneurons at both excitatory and
      inhibitory postsynaptic sites. Overexpression of ErbB4 postsynaptically enhances
      size but not number of presynaptic inputs. Conversely, knockdown of ErbB4 using
      shRNA decreases the size of presynaptic inputs, demonstrating a specific role for
      endogenous ErbB4 in synapse maturation. Using ErbB4 mutant constructs, we
      demonstrate that ErbB4-mediated synapse maturation requires its extracellular
      domain, whereas its tyrosine kinase activity is dispensable for this process. We
      also demonstrate that depletion of ErbB4 decreases the number of primary neurites
      and that stimulation of ErbB4 using a soluble form of NRG1 results in exuberant
      dendritic arborization through activation of the tyrosine kinase domain of ErbB4
      and the phosphoinositide 3-kinase pathway. These findings demonstrate that
      NRG1/ErbB4 signaling differentially regulates synapse maturation and dendritic
      morphology via two distinct mechanisms involving trans-synaptic signaling and
      tyrosine kinase activity, respectively.

PMID- 18819925
TI  - Projection structure of a member of the amino acid/polyamine/organocation
      transporter superfamily.
AB  - The L-arginine/agmatine antiporter AdiC is a key component of the arginine
      dependent extreme acid resistance system of Escherichia coli. Phylogenetic
      analysis indicated that AdiC belongs to the amino acid/polyamine/organocation
      (APC) transporter superfamily having sequence identities of 15-17% to eukaryotic
      and human APC transporters. For functional and structural characterization, we
      cloned, overexpressed, and purified wild-type AdiC and the point mutant AdiC
      W293L, which is unable to bind and consequently transport L-arginine. Purified
      detergent-solubilized AdiC particles were dimeric. Reconstitution experiments
      yielded two-dimensional crystals of AdiC-W293L diffracting beyond 6 angstroms
      resolution from which we determined the projection structure at 6.5 angstroms
      resolution. The projection map showed 10-12 density peaks per monomer and
      suggested mainly tilted helices with the exception of one distinct perpendicular
      membrane spanning alpha-helix. Comparison of AdiC-W293L with the projection map
      of the oxalate/formate antiporter from Oxalobacter formigenes, a member from the
      major facilitator superfamily, indicated different structures. Thus, two
      dimensional crystals of AdiC-W293L yielded the first detailed view of a transport
      protein from the APC superfamily at sub-nanometer resolution.

PMID- 18819926
TI  - Introduction of the chloroplast redox regulatory region in the yeast ATP synthase
      impairs cytochrome c oxidase.
AB  - The ATP synthase is under a number of mechanisms of regulation. The chloroplast
      ATPase has a unique mode of regulation in which activity is controlled by the
      redox state in the organelle. This mode of regulation is determined by a small
      unique region within the gamma-subunit and this region contains two cysteine
      residues. Introduction of this region within the yeast gamma-subunit causes a
      defect in oxidative phosphorylation. Oxidative phosphorylation is restored if the
      cysteine residues are replaced with serine. Biochemical analysis of the chimeric
      mitochondrial ATPase indicates that the ATP synthase is not largely altered with
      the cysteine residues in either the oxidized or reduced states. However, the
      level and activity of cytochrome c oxidase are decreased by about 90%, whereas
      that of NADH dehydrogenase and cytochrome c reductase are unchanged as compared
      with the wild-type enzymes. The level and activity of cytochrome c oxidase are
      restored with replacement of the cysteine residues with serine in the regulatory
      region. These results indicate that the chimeric ATP synthase containing
      cysteine, but not serine, decreases the expression or assembly of cytochrome c
      oxidase with little effect on the activity of the ATP synthase.

PMID- 18819927
TI  - Autoubiquitination of BCA2 RING E3 ligase regulates its own stability and affects
      cell migration.
AB  - Accumulating evidence suggests that ubiquitination plays a role in cancer by
      changing the function of key cellular proteins. Previously, we isolated BCA2 gene
      from a library enriched for breast tumor mRNAs. The BCA2 protein is a RING-type
      E3 ubiquitin ligase and is overexpressed in human breast tumors. In order to
      deduce the biochemical and biological function of BCA2, we searched for BCA2
      binding partners using human breast and fetal brain cDNA libraries and
      BacterioMatch two-hybrid system. We identified 62 interacting partners, the
      majority of which were found to encode ubiquitin precursor proteins including
      ubiquitin C and ubiquitin A-52. Using several deletion and point mutants, we
      found that the BCA2 zinc finger (BZF) domain at the NH(2) terminus specifically
      binds ubiquitin and ubiquitinated proteins. The autoubiquitination activity of
      BCA2, RING-H2 mutant, BZF mutant, and various lysine mutants of BCA2 were
      investigated. Our results indicate that the BCA2 protein is strongly
      ubiquitinated and no ubiquitination is detected with the BCA2 RING-H2 mutant,
      indicating that the RING domain is essential for autoubiquitination. Mutation of
      the K26 and K32 lysines in the BZF domain also abrogated autoubiquitination
      activity. Interestingly, mutation of the K232 and K260 lysines in and near the
      RING domain resulted in an increase in autoubiquitination activity. Additionally,
      in cellular migration assays, BCA2 mutants showed altered cell motility compared
      with wild-type BCA2. On the basis of these findings, we propose that BCA2 might
      be an important factor regulating breast cancer cell migration/metastasis. We put
      forward a novel model for BCA2 E3 ligase-mediated cell regulation.

PMID- 18819928
TI  - A Key role for cyclic AMP-responsive element binding protein in hypoxia-mediated
      activation of the angiogenesis factor CCN1 (CYR61) in Tumor cells.
AB  - Hypoxia is a prominent feature of solid tumors known to contribute to malignant
      progression and therapeutic resistance. Cancer cells adapt to hypoxia using
      various pathways, allowing tumors to thrive in a low oxygen state. Induction of
      new blood vessel formation via the secretion of proangiogenic factors is one of
      the main adaptive responses engaged by tumor cells under hypoxic conditions.
      Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that plays a pivotal
      role in mediating such responses. In addition, several other transcription
      factors have also been implicated in hypoxic gene regulation, either
      independently or in cooperation with HIF-1. In this work, we show that the
      expression of the angiogenesis-related, immediate early gene CCN1 (formerly known
      as CYR61), considered to be involved in tumor growth and invasiveness, is
      enhanced upon hypoxia stress primarily in a protein kinase A and cyclic AMP
      responsive element binding protein (CREB) and CRE-dependent manner in various
      cell lines. The hypoxia-mediated activation of the CCN1 promoter is independent
      of HIF-1 and HIF-2, as shown by small interfering RNA knockdown. We identify the
      cis element in the mouse CCN1 promoter responsible for CREB binding to be one of
      two partial CRE sites present in the promoter. Moreover, we report for the first
      time that CREB-mediated CCN1 transcription is enhanced in hypoxic regions of
      tumors in vivo. Identifying and characterizing the molecular mechanisms that
      govern the response of tumors to hypoxia may be instrumental to identify the
      tumors that will respond favorably to inhibition of angiogenesis and thus lead to
      the development of treatments that could complement hypoxia-inducing treatment
      modalities.

PMID- 18819929
TI  - Up-regulation of Rho/ROCK signaling in sarcoma cells drives invasion and
      increased generation of protrusive forces.
AB  - Tumor cell invasion is the most critical step of metastasis. Determination of the
      mode of invasion within the particular tumor is critical for effective cancer
      treatment. Protease-independent amoeboid mode of invasion has been described in
      carcinoma cells and more recently in sarcoma cells on treatment with protease
      inhibitors. To analyze invasive behavior, we compared highly metastatic sarcoma
      cells with parental nonmetastatic cells. The metastatic cells exhibited a
      functional up-regulation of Rho/ROCK signaling and, similarly to carcinoma cells,
      an amoeboid mode of invasion. Using confocal and traction force microscopy, we
      showed that an up-regulation of Rho/ROCK signaling leads to increased
      cytoskeletal dynamics, myosin light chain localization, and increased tractions
      at the leading edge of the cells and that all of these contributed to increased
      cell invasiveness in a three-dimensional collagen matrix. We conclude that cells
      of mesenchymal origin can use the amoeboid nonmesenchymal mode of invasion as
      their primary invading mechanism and show the dependence of ROCK-mediated
      amoeboid mode of invasion on the increased capacity of cells to generate force.

PMID- 18819930
TI  - Sox7 Is an independent checkpoint for beta-catenin function in prostate and colon
      epithelial cells.
AB  - The presence of somatic beta-catenin mutations in some prostate cancers implies
      that aberrant WNT signaling is involved in the cancer development. Although beta
      catenin stability is regulated by a multicomponent destruction complex,
      mutational alterations of beta-catenin or other components of the destruction
      complexes are rare in prostate tumors. Therefore, beta-catenin may be regulated
      by another protein in the prostate. In fact, recent linkage and somatic deletion
      analyses in prostate cancers reveal a 1.4-Mb candidate tumor suppressor locus on
      8p23.1, which includes the Sox7 gene. Here we show that Sox7 protein expression
      was indeed down-regulated in 47% (15 of 32) of prostate adenocarcinomas. In
      addition, Sox7 mRNA was down-regulated in 60% of snap-frozen tumors. This down
      regulation was found to be due to tumor-specific promoter hypermethylation, which
      was present in 48% (10 of 21) of primary prostate tumors and 44% (11 of 25) of
      prostate cancer cell lines/xenografts. We discovered that Sox7 protein physically
      interacts with beta-catenin and suppresses beta-catenin-mediated transcription by
      depleting active beta-catenin. Furthermore, in HCT116 colorectal cancer cell
      lines with Sox7 inactivation, ectopic Sox7 expression suppressed cell
      proliferation and inhibited transcription that was activated by an endogenous
      mutant beta-catenin. Although nearly all colorectal cancers contain mutations in
      beta-catenin or adenomatous polyposis coli/axin, epigenetic silencing of Sox7 was
      still observed. These data suggest that Sox7 is a tumor suppressor that functions
      as an independent checkpoint for beta-catenin transcriptional activity.
      Inactivation of Sox7 could promote the development of a majority of colorectal
      tumors and approximately half of prostate tumors.

PMID- 18819931
TI  - IFN-induced protein with tetratricopeptide repeats 2 inhibits migration activity
      and increases survival of oral squamous cell carcinoma.
AB  - The function of the IFN-stimulated gene family protein, IFN-induced protein with
      tetratricopeptide repeats 2 (IFIT2), is poorly understood. Here, we report that
      IFIT2 colocalizes with cytokeratin 18 in oral squamous cell carcinoma (OSCC)
      cells. Treatment of OSCC cells with IFN-beta significantly increased the
      expression of IFIT2 and remarkably inhibited cell migration. To further explore
      the effect of IFIT2 on cell migration, IFIT2 expression was either silenced with
      a small interfering RNA or increased by ectopic expression. IFIT2 knockdown in
      OSCC cells led to a significantly higher level of migration in vitro (P < 0.05)
      compared with control cells; by contrast, IFIT2 overexpression led to a
      significantly lower level of migration in vitro (P < 0.05).
      Immunohistochemically, 71.4% of OSCC tissues had elevated IFIT2 protein levels
      compared with noncancerous matched tissues. Elevated IFIT2 protein expression was
      positively associated with tumor differentiation status and inversely associated
      with nodal stage in OSCC specimens (P < 0.05). Higher IFIT2 protein levels in
      tumor tissues were also associated with better patient survival (P < 0.01). Our
      present study shows an inverse correlation between IFIT2 expression and cell
      migration, suggesting that IFIT2 plays an important role in inhibiting this
      process and that its expression may be associated with better prognosis in
      patients with OSCC.

PMID- 18819932
TI  - The retinoblastoma protein tumor suppressor is important for appropriate
      osteoblast differentiation and bone development.
AB  - Mutation of the retinoblastoma (RB) tumor suppressor gene is strongly linked to
      osteosarcoma formation. This observation and the documented interaction between
      the retinoblastoma protein (pRb) and Runx2 suggests that pRb is important in bone
      development. To assess this hypothesis, we used a conditional knockout strategy
      to generate pRb-deficient embryos that survive to birth. Analysis of these
      embryos shows that Rb inactivation causes the abnormal development and impaired
      ossification of several bones, correlating with an impairment in osteoblast
      differentiation. We further show that Rb inactivation acts to promote osteoblast
      differentiation in vitro and, through conditional analysis, establish that this
      occurs in a cell-intrinsic manner. Although these in vivo and in vitro
      differentiation phenotypes seem paradoxical, we find that Rb-deficient
      osteoblasts have an impaired ability to exit the cell cycle both in vivo and in
      vitro that can explain the observed differentiation defects. Consistent with this
      observation, we show that the cell cycle and the bone defects in Rb-deficient
      embryos can be suppressed by deletion of E2f1, a known proliferation inducer that
      acts downstream of Rb. Thus, we conclude that pRb plays a key role in regulating
      osteoblast differentiation by mediating the inhibition of E2F and consequently
      promoting cell cycle exit.

PMID- 18819933
TI  - The circadian gene NPAS2, a putative tumor suppressor, is involved in DNA damage
      response.
AB  - Apart from regulating sleep and wakefulness, the circadian system may play an
      important role in other biological processes, including pathways involved in
      tumorigenesis. Two genetic association studies recently conducted by our lab have
      shown that a missense mutation in neuronal PAS domain protein 2 (NPAS2), a core
      circadian gene and transcriptional regulator, is significantly associated with
      risk of breast cancer and non-Hodgkin's lymphoma. Our current functional analyses
      provide the first in vitro evidence further demonstrating that cells with RNA
      interference-mediated depletion of NPAS2 fail to exhibit the expected cell cycle
      delay in response to mutagen treatment. DNA repair capacity, as measured by the
      comet assay, is also impaired. Moreover, a pathway-based PCR expression array of
      genes important for DNA damage signaling showed that knockdown of NPAS2
      significantly represses the expression of several cell cycle and DNA repair
      genes. Thus, NPAS2 may play a role in tumorigenesis by affecting expression of
      cancer-related genes and could be considered a novel tumor suppressor.

PMID- 18819935
TI  - Repression of the desmocollin 2 gene expression in human colon cancer cells is
      relieved by the homeodomain transcription factors Cdx1 and Cdx2.
AB  - Desmosomes are intracellular junctions that provide strong cell-cell adhesion in
      epithelia and cardiac muscle. Their disruption causes several human diseases and
      contributes to the epithelial-to-mesenchymal transition observed in cancer.
      Desmocollin 2 (DSC2) is a cadherin superfamily member and a critical component of
      desmosomes found in intestinal epithelium. However, the mechanism regulating DSC2
      gene expression in intestinal cells is not known. Cdx1 and Cdx2 are homeodomain
      transcription factors that regulate intestine-specific gene expression. Cdx
      expression in the past has been associated with the induction of desmosomes. We
      now show that the DSC2 gene is a transcriptional target for Cdx1 and Cdx2. Colon
      cancer cell lines retaining Cdx2 expression typically express DSC2. Restoration
      of Cdx expression in Colo 205 cells induced DSC2 mRNA and protein and the
      formation of desmosomes. The 5'-flanking region of the DSC2 promoter contains two
      consensus Cdx-binding sites. Electrophoretic mobility shift assays show that Cdx1
      and Cdx2 bind these sites in vitro, and chromatin immunoprecipitation confirmed
      Cdx2 binding in vivo. DSC2 promoter truncations established that these regions
      are Cdx responsive. The truncations also identify a region of the promoter in
      which potent transcriptional repressors act. This repressor activity is relieved
      by Cdx binding. We conclude that the homeodomain transcription factors Cdx1 and
      Cdx2 regulate DSC2 gene expression in intestinal epithelia by reversing the
      actions of a transcriptional repressor. The regulation of desmosomal junctions by
      Cdx contributes to normal intestinal epithelial columnar morphology and likely
      antagonizes the epithelial-to-mesenchymal transition necessary for the metastasis
      of colon cancer cells in humans.

PMID- 18819934
TI  - Sphingosine-1-phosphate and interleukin-1 independently regulate plasminogen
      activator inhibitor-1 and urokinase-type plasminogen activator receptor
      expression in glioblastoma cells: implications for invasiveness.
AB  - Glioblastoma multiforme is an invasive primary brain tumor, which evades the
      current standard treatments. The invasion of glioblastoma cells into healthy
      brain tissue partly depends on the proteolytic and nonproteolytic activities of
      the plasminogen activator system proteins, including the urokinase-type
      plasminogen activator (uPA), plasminogen activator inhibitor 1 (PAI-1), and a
      receptor for uPA (uPAR). Here we show that sphingosine-1-phosphate (S1P) and the
      inflammatory mediator interleukin-1 (IL-1) increase the mRNA and protein
      expression of PAI-1 and uPAR and enhance the invasion of U373 glioblastoma cells.
      Although IL-1 enhanced the expression of sphingosine kinase 1 (SphK1), the enzyme
      that produces S1P, down-regulation of SphK1 had no effect on the IL-1-induced
      uPAR or PAI-1 mRNA expression, suggesting that these actions of IL-1 are
      independent of S1P production. Indeed, the S1P-induced mRNA expression of uPAR
      and PAI-1 was blocked by the S1P(2) receptor antagonist JTE013 and by the down
      regulation of S1P(2) using siRNA. Accordingly, the inhibition of mitogen
      activated protein kinase/extracellular signal-regulated kinase kinase 1/2 and Rho
      kinase, two downstream signaling cascades activated by S1P(2), blocked the
      activation of PAI-1 and uPAR mRNA expression by S1P. More importantly, the
      attachment of glioblastoma cells was inhibited by the addition of exogenous PAI-1
      or siRNA to uPAR, whereas the invasion of glioblastoma cells induced by S1P or IL
      1 correlated with their ability to enhance the expression of PAI-1 and uPAR.
      Collectively, these results indicate that S1P and IL-1 activate distinct pathways
      leading to the mRNA and protein expression of PAI-1 and uPAR, which are important
      for glioblastoma invasiveness.

PMID- 18819936
TI  - Progesterone receptor-B regulation of insulin-like growth factor-stimulated cell
      migration in breast cancer cells via insulin receptor substrate-2.
AB  - Progesterone action contributes to the signaling of many growth factor pathways
      relevant to breast cancer tumor biology, including the insulin-like growth factor
      (IGF) system. Previous work has shown that insulin receptor substrate-2 (IRS-2)
      but not IRS-1 levels were regulated by progestin in progesterone receptor-B (PR
      B) isoform expressing MCF-7 cells (C4-12 PR-B). Furthermore, type 1 IGF receptor
      (IGF1R) signaling via IRS-2 correlated with the increased cell migration observed
      in a number of breast cancer cell lines. Consequently, in this study, we examined
      whether the elevation of IRS-2 protein induced by progestin was sufficient to
      promote IGF-I-stimulated cell motility. Treatment of C4-12 PR-B cells with
      progestin shifted the balance of phosphorylation from IRS-1 to IRS-2 in response
      to IGF-I. This shift in IRS-2 activation was associated with enhanced migration
      in C4-12 PR-B cells pretreated with progestin, but had no effect on cell
      proliferation or survival. Treatment of C4-12 PR-B cells with RU486, an
      antiprogestin, inhibited IGF-induced cell migration. Attenuation of IRS-2
      expression using small interfering RNA resulted in decreased IGF-stimulated
      motility. In addition, IRS-2 knockdown resulted in an abrogation of PKB/Akt
      phosphorylation but not mitogen-activated protein kinase. Consequently, LY294002,
      a phosphoinositide-3-kinase inhibitor, abolished IGF-induced cell motility in
      progestin-treated C4-12 PR-B cells. These data show a role for the PR in
      functionally promoting growth factor signaling, showing that levels of IRS
      proteins can determine IGF-mediated biology, PR-B signaling regulates IRS-2
      expression, and that IRS-2 can mediate IGF-induced cell migration via
      phosphoinositide-3-kinase in breast cancer cells.

PMID- 18819938
TI  - Genome annotation in the presence of insertional RNA editing.
AB  - MOTIVATION: Insertional RNA editing renders gene prediction very difficult
      compared to organisms without such RNA editing. A case in point is the
      mitochondrial genome of Physarum polycephalum in which only about one-third of
      the number of genes that are to be expected given its length are annotated. Thus,
      gene prediction methods that explicitly take into account insertional editing are
      needed for successful annotation of such genomes. RESULTS: We annotate the
      mitochondrial genome of P.polycephalum using several different approaches for
      gene prediction in organisms with insertional RNA editing. We computationally
      validate our annotations by comparing the results from different methods against
      each other and as proof of concept experimentally validate two of the newly
      predicted genes. We more than double the number of annotated putative genes in
      this organism and find several intriguing candidate genes that are not expected
      in a mitochondrial genome. AVAILABILITY: The C source code of the programs
      described here are available upon request from the corresponding author.

PMID- 18819937
TI  - 2,2-bis(4-chlorophenyl)-1,1-dichloroethylene stimulates androgen independence in
      prostate cancer cells through combinatorial activation of mutant androgen
      receptor and mitogen-activated protein kinase pathways.
AB  - Therapy resistance represents a major clinical challenge in disseminated prostate
      cancer for which only palliative treatment is available. One phenotype of therapy
      resistant tumors is the expression of somatic, gain-of-function mutations of the
      androgen receptor (AR). Such mutant receptors can use noncanonical endogenous
      ligands (e.g., estrogen) as agonists, thereby promoting recurrent tumor
      formation. Additionally, selected AR mutants are sensitized to the estrogenic
      endocrine-disrupting compound (EDC) bisphenol A, present in the environment.
      Herein, screening of additional EDCs revealed that multiple tumor-derived AR
      mutants (including T877A, H874Y, L701H, and V715M) are sensitized to activation
      by the pesticide 2,2-bis(4-chlorophenyl)-1,1-dichloroethylene (DDE), thus
      indicating that this agent may impinge on AR signaling in cancer cells. Further
      investigation showed that DDE induced mutant AR recruitment to the prostate
      specific antigen regulatory region, concomitant with an enhancement of target
      gene expression, and androgen-independent proliferation. By contrast, neither AR
      activation nor altered cellular proliferation was observed in cells expressing
      wild-type AR. Activation of signal transduction pathways was also observed based
      on rapid phosphorylation of mitogen-activated protein kinase (MAPK) and
      vasodilator-stimulated phosphoprotein, although only MAPK activation was
      associated with DDE-induced cellular proliferation. Functional analyses showed
      that both mutant AR and MAPK pathways contribute to the proliferative action of
      DDE, as evidenced through selective abrogation of each pathway. Together, these
      data show that exposure to environmentally relevant doses of EDCs can promote
      androgen-independent cellular proliferation in tumor cells expressing mutant AR
      and that DDE uses both mutant AR and MAPK pathways to exert its mitogenic
      activity.

PMID- 18819939
TI  - Identifying differentially expressed subnetworks with MMG.
AB  - BACKGROUND: Mixture model on graphs (MMG) is a probabilistic model that
      integrates network topology with (gene, protein) expression data to predict the
      regulation state of genes and proteins. It is remarkably robust to missing data,
      a feature particularly important for its use in quantitative proteomics. A new
      implementation in C and interfaced with R makes MMG extremely fast and easy to
      use and to extend. AVAILABILITY: The original implementation (Matlab) is still
      available from http://www.dcs.shef.ac.uk/~guido/; the new implementation is
      available from http://wrightlab.group.shef.ac.uk/people_noirel.htm, from CRAN,
      and has been submitted to BioConductor, http://www.bioconductor.org/.

PMID- 18819940
TI  - Databases, data tombs and dust in the wind.
AB  - As biomedical data accumulates, the need to store, share and organize it grows.
      Consequently, the number of Internet-accessible databases has been rapidly
      growing on an annual basis. Bioinformatics regularly publishes descriptions of
      biomedically relevant databases, Nucleic Acids Research has published an annual
      database issue since 1996 and now a new open-access journal, DATABASE: The
      Journal of Biological DATABASEs and Curation, will soon be launched by Oxford
      University Press in 2009 (http://www.oxfordjournals.org/our_journals/databa/).
      Since databases can be made publicly available on the Internet without
      publication, it is worth considering what factors prioritize publication of
      database descriptions in a peer-reviewed journal. In general, publication of a
      database description in a journal advertises it as a valuable resource for
      scientific research. Implicitly, it is assumed that this resource is publicly
      available (most likely for free) and will be maintained. However, therein lies
      the problem: DATABASE papers are simply not of the same nature as regular
      research articles. Over time, some databases simply become inaccessible, some are
      created but not maintained or updated, and some databases are never used
      (Galperin, 2006). Thus, for database creators, reviewers and journal editors,
      there are several additional considerations to judge, prior to publication, how
      potentially valuable these new databases may be.

PMID- 18819941
TI  - Ankle-brachial index and extent of atherosclerosis in patients from the Middle
      East (the AGATHA-ME study): a cross-sectional multicenter study.
AB  - To assess the extent of atherothrombosis and the use of the ankle-brachial index
      (ABI) in populations from the Middle East, we conducted a multicenter study
      similar to AGATHA (a Global Atherothrombosis Assessment), AGATHA-ME, which
      included 1341 patients from 18 centers from 5 countries (United Arab Emirates,
      Kuwait, Qatar, Bahrain, and Oman). Patients were assigned to 2 groups: the with
      disease and at-risk groups. Abnormal ABI (< or =0.9) was seen in 31.5% of at-risk
      patients and 28.2% of with-disease patients. Patients with peripheral arterial
      disease had the highest frequency of abnormal ABI (77.6%), with 97.8 negative
      predictive value. The AGATHA-ME study confirms that atherothrombosis disease
      often occurs at more than 1 site. The ABI is related to the risk factor profile
      and to the site and extent of atherothrombosis. Gender and diabetes mellitus are
      associated with the worst parameters.

PMID- 18819943
TI  - Impaired subjective health status in chronic adrenal insufficiency: impact of
      different glucocorticoid replacement regimens.
AB  - CONTEXT: Recent studies have suggested that current glucocorticoid replacement
      therapies fail to fully restore well-being in patients with adrenal insufficiency
      (AI). OBJECTIVE: To investigate the effect of different glucocorticoid
      preparations used for replacement therapy on subjective health status (SHS) in
      AI. DESIGN AND PATIENTS: In a cross-sectional study, primary and secondary AI
      patients were contacted by mail. Individual glucocorticoid replacement regimens,
      underlying diagnoses and comorbidities were verified by questionnaires and review
      of medical records. Patients were asked to complete three validated self
      assessment questionnaires (Short Form 36 (SF-36), Giessen Complaint List (GBB
      24), and Hospital Anxiety and Depression Scale). Results were compared with sex-
      and age-matched controls drawn from the questionnaire-specific reference cohort.
      RESULTS: Of the 883 patients identified, 526 agreed to participate in the study.
      Completed questionnaire sets were available from 427 patients (primary AI n=232;
      secondary AI n=195). AI patients showed significantly impaired SHS compared with
      controls irrespective of the glucocorticoid used for replacement. The only
      difference in SHS between patients on prednisolone (PR) and hydrocortisone (all
      patients and sub-analysis for primary AI) was significant higher bodily pain
      (lower Z-score in SF-36) in patients on PR (P<0.05, P<0.01 respectively). In
      patients with secondary AI, the PR group showed significantly (P<0.05) less heart
      complaints (lower Z-score) in the GBB questionnaire compared with the cortisone
      acetate group. CONCLUSIONS: Glucocorticoid replacement therapy with PR seems to
      be equivalent to hydrocortisone regarding SHS in patients with AI. However, SHS
      remains impaired in all patient groups suggesting a need for further improved
      glucocorticoid replacement strategies.

PMID- 18819942
TI  - The use of nerve and muscle biopsy in the diagnosis of vasculitis: a 5 year
      retrospective study.
AB  - INTRODUCTION: Peripheral nerve vasculitis is an important condition which can be
      diagnostically challenging and is one of the principal current indications for
      nerve and muscle biopsy. Previous studies have suggested that combined nerve and
      muscle biopsy (usually of the superficial peroneal nerve and peroneus brevis
      muscle) produces a higher diagnostic yield than nerve biopsy alone in the
      investigation of vasculitis. OBJECTIVE: To determine whether in our two centres
      combined nerve (usually the sural) and muscle (usually the vastus lateralis)
      biopsy improved diagnostic yield compared with nerve biopsy alone. METHODS: We
      interrogated our database of all nerve biopsies (usually of the sural nerve)
      performed at our institutions over 5 years and identified 53 cases of biopsy
      proven peripheral nerve vasculitis. Clinicopathological and neurophysiological
      data in these patients were reviewed. RESULTS: The most common clinical
      presentation was with a painful asymmetric axonal polyneuropathy or mononeuritis
      multiplex (66% of cases). Nerve biopsy demonstrated definite vasculitis in 36%,
      probable vasculitis in 62% and no vasculitis in 2% of cases. In 24 patients a
      muscle biopsy (usually the vastus lateralis) was also performed and vasculitis
      was demonstrated in 46% of these (in 13% showing definite and 33% probable
      vasculitis). There was only one patient in whom vasculitis was demonstrated in
      muscle but not in peripheral nerve. CONCLUSION: Combined nerve (usually sural)
      and vastus lateralis muscle biopsy did not significantly increase the diagnostic
      yield compared with nerve biopsy alone. A sensible approach to the diagnosis of
      peripheral nerve vasculitis is to choose a nerve to biopsy which is clinically
      affected and amenable to biopsy. If the sural nerve is chosen, the data suggest
      that it is not routinely worth doing a vastus lateralis biopsy at the same time,
      whereas if the superficial peroneal nerve is chosen, it seems appropriate to do a
      combined superficial peroneal nerve and peroneus brevis biopsy. It is still not
      known if both the sural and superficial peroneal nerves are involved clinically
      which one gives the higher yield if biopsied.

PMID- 18819944
TI  - Problems with GH assays and strategies toward standardization.
AB  - Disorders affecting GH secretion--either GH deficiency or GH excess (acromegaly)-
      are biochemically defined through peak or nadir concentrations of human GH in
      response to dynamic tests. Immunoassays employing polyclonal or monoclonal
      antibodies are routinely used for the analysis of GH concentrations, and many
      different assays are available on the market today. Unfortunately, the actual
      value reported for the GH concentration in a specific patient's sample to a large
      extent depends on the assay method used by the respective laboratory. Variability
      between assay results exceeds 200%, limiting the applicability of consensus
      guidelines in clinical practice. Reasons for the heterogeneity in GH assay
      results include the heterogeneity of the analyte itself, the availability of
      different preparations for calibration, and the interference from matrix
      components such as GH-binding protein. Furthermore, the reporting of results in
      mass units or international units together with the application of variable
      conversion factors led to confusion. International collaborations proposed
      measures to improve the comparability of assay results, recommending the use of a
      single, recombinant calibrator for all assays and reporting only in mass units as
      first steps. However, because of the differences in epitope specificity of
      antibodies used in different assays, method-specific cut-off levels for dynamic
      tests might remain necessary to correctly interpret and compare results from
      different laboratories.

PMID- 18819945
TI  - Mortality from thyroid cancer in patients with hyperthyroidism: the Theagenion
      Cancer Hospital experience.
AB  - BACKGROUND: Thyroid carcinoma has been reported in patients operated for
      different types of hyperthyroidism and the probability of a hot nodule being
      malignant seems to be low. The aim of the present study was to explore the
      relationship between thyroid cancer, hyperthyroidism and outcome in a large
      cohort of patients who presented to a tertiary cancer centre in Northern Greece.
      PATIENTS: Among 720 patients treated for thyroid cancer, 60 had a concomitant
      diagnosis of hyperthyroidism due to Graves' disease (n=14), solitary autonomous
      adenoma (n=17), or multinodular goiter (n=29). Adverse prognostic factors were
      common in patients with a previous history of hyperthyroidism at the time of
      diagnosis of thyroid cancer, including cases where the cancer was discovered
      coincidentally after thyroid surgery for hyperthyroidism and cases where tumor
      size was more than 10 mm. RESULTS: In 10 out of 17 patients with hyperthyroidism
      due to solitary autonomous adenomas, the tumor was located within the hot nodule
      and two of these patients developed local and distant metastases and died from
      the disease 4 and 15 years after thyroidectomy. CONCLUSION: Clinicians managing
      patients with hyperthyroidism need to be aware of the possible increased risk of
      thyroid cancer in this patient group.

PMID- 18819946
TI  - Hyperleptinaemia rather than fasting hyperinsulinaemia is associated with obesity
      following hypothalamic damage in children.
AB  - BACKGROUND: Obesity following hypothalamic damage is often severe and resistant
      to lifestyle changes. Disruption of hypothalamic feedback mechanisms that
      maintain energy homeostasis may be responsible for this intractable obesity.
      Adipocytokines including insulin and leptin are also known to be important
      regulators of appetite and weight. OBJECTIVE: To investigate the role of insulin,
      leptin, adiponectin and resistin in the aetiology of hypothalamic obesity (HO).
      DESIGN: This was a cross-sectional study of three groups of children, those with
      HO, congenital hypopituitarism (CH) and simple obesity (SO). RESULTS: A total of
      69 children (HO=28, CH=18, SO=23) had leptin, resistin, adiponectin and insulin
      measured. Although fasting hyperinsulinaemia and insulin resistance were
      demonstrated, no differences in insulin or insulin resistance were seen between
      the groups. The HO group, however, had higher levels of leptin, adiponectin and
      resistin, which persisted even after adjusting for fat mass, compared with the
      other groups (P<0.05). CONCLUSION: No differences in fasting hyperinsulinaemia or
      insulin resistance were seen between the groups; however, leptin levels are
      elevated, even after adjusting for fat mass, suggesting that an element of leptin
      resistance is associated with HO. This is consistent with the inability of leptin
      to act on the hypothalamus, either due to transport across the blood-brain
      barrier or dysfunctional receptors. The lack of response to leptin may be more
      important in the development of obesity in these individuals, and the fasting
      hyperinsulinaemia is a result of the increased adipose tissue rather than the
      cause of the weight gain.

PMID- 18819947
TI  - Is shade beneficial for mediterranean shrubs experiencing periods of extreme
      drought and late-winter frosts?
AB  - BACKGROUND AND AIMS: Plants are naturally exposed to multiple, frequently
      interactive stress factors, most of which are becoming more severe due to global
      change. Established plants have been reported to facilitate the establishment of
      juvenile plants, but net effects of plant-plant interactions are difficult to
      assess due to complex interactions among environmental factors. An investigation
      was carried out in order to determine how two dominant evergreen shrubs (Quercus
      ilex and Arctostaphylos uva-ursi) co-occurring in continental, Mediterranean
      habitats respond to multiple abiotic stresses and whether the shaded understorey
      conditions ameliorate the negative effects of drought and winter frosts on the
      physiology of leaves. METHODS: Microclimate and ecophysiology of sun and shade
      plants were studied at a continental plateau in central Spain during 2004-2005,
      with 2005 being one of the driest and hottest years on record; several late
      winter frosts also occurred in 2005. KEY RESULTS: Daytime air temperature and
      vapour pressure deficit were lower in the shade than in the sun, but soil
      moisture was also lower in the shade during the spring and summer of 2005, and
      night-time temperatures were higher in the shade. Water potential, photochemical
      efficiency, light-saturated photosynthesis, stomatal conductance and leaf 13C
      composition differed between sun and shade individuals throughout the seasons,
      but differences were species specific. Shade was beneficial for leaf-level
      physiology in Q. ilex during winter, detrimental during spring for both species,
      and of little consequence in summer. CONCLUSIONS: The results suggest that
      beneficial effects of shade can be eclipsed by reduced soil moisture during dry
      years, which are expected to be more frequent in the most likely climate change
      scenarios for the Mediterranean region.

PMID- 18819948
TI  - The impact of biochemistry vs. population membership on floral scent profiles in
      colour polymorphic Hesperis matronalis.
AB  - BACKGROUND AND AIMS: Studies of floral scent evolution often attribute variation
      in floral scent to differences in pollinator behaviour, ignoring the potential
      for shared biochemistry between floral scent and floral colour to dictate
      patterns of phenotypic variation in scent production. To determine the relative
      effects of shared biochemistry and/or localized population-level phenomena on
      floral scent phenotype, floral scent composition and emission rate were examined
      in five wild populations of colour polymorphic Hesperis matronalis
      (Brassicaceae). METHODS: Floral scent was collected by in situ dynamic headspace
      extraction on purple and white colour morphs in each of five wild populations.
      Gas chromatography-mass spectroscopy of extracts allowed determination of floral
      scent composition and emission rate for all individuals, which were examined by
      non-metric multidimensional scaling and analysis of variance (ANOVA),
      respectively, to determine the contributions of floral colour and population
      membership to scent profile variation. KEY RESULTS: Despite the fact that colour
      morph means were very similar in some populations and quite different in other
      populations, colour morphs within populations did not differ from each other in
      terms of scent composition or emission rate. Populations differed significantly
      from one another in terms of both floral scent composition and emission rate.
      CONCLUSIONS: Shared biochemistry alone cannot explain the variation in floral
      scent phenotype found for H. matronalis. Such a result may suggest that the
      biochemical association between floral scent and floral colour is complex or
      dependent on genetic background. Floral scent does vary significantly with
      population membership; several factors, including environmental conditions,
      founder effects and genetics, may account for this differentiation and should be
      considered in future studies.

PMID- 18819949
TI  - Comparative anatomy and morphology of nectar-producing Melastomataceae.
AB  - BACKGROUND AND AIMS: Most neotropical Melastomataceae have bee-pollinated flowers
      with poricidal anthers. However, nectar rewards are known to be produced in about
      80 species in eight genera from four different tribes. These nectar-producing
      species are pollinated by both vertebrates and invertebrates. METHODS: The floral
      morphology and anatomy of 14 species was studied in six genera of nectar
      producing Melastomataceae (Blakea, Brachyotum, Charianthus, Huilaea, Meriania and
      Miconia). Anatomical methods included scanning electron microscopy, and serial
      sections of paraffin-embedded flowers. KEY RESULTS: All vertebrate-pollinated
      melastome flowers have petals that do not open completely at anthesis, thus
      forming a pseudo-tubular corolla, while closely related species that are bee
      pollinated have rotate or reflexed corollas. In most species, nectar secretion is
      related to stomatal or epidermal nectaries and not filament slits as previously
      reported. Moreover, the nectar is probably supplied by large vascular bundles
      near the release area. Blakea and Huilaea have nectary stomata located upon the
      dorsal anther connective appendages. Brachyotum also has nectary stomata on the
      anther connectives, but these are distributed lengthwise along most of the
      connective. Meriania may release nectar through the anther connective, but has
      additional nectary stomata on the inner walls of the hypanthium. Miconia has
      nectary stomata on the ovary apex. Charianthus nectaries were not found, but
      there is circumstantial evidence that nectar release occurs through the epidermis
      at the apex of the ovary and the lower portions of the inner wall of the
      hypanthium. CONCLUSIONS: Nectar release in Melastomataceae is apparently related
      to nectary stomata and not filament slits. The presence of nectary stomata on
      stamens and on ovary apices in different lineages suggests that the acquisition
      of nectaries is a derived condition. Nectary location also supports a derived
      condition, because location is strongly consistent within each genus, but differs
      between genera.

PMID- 18819950
TI  - Ancient Chinese literature reveals pathways of eggplant domestication.
AB  - BACKGROUND AND AIMS: Changes in key traits occurring during the processes of
      plant domestication have long been subjects of debate. Only in the case of
      genetic analysis or with extensive plant remains can specific sets of changes be
      documented. Historical details of the plant domestication processes are rare and
      other evidence of morphological change can be difficult to obtain, especially for
      those vegetables that lack a substantial body of archaeological data. Botanical
      records chronicled in the ancient literature of established ancient
      civilizations, such as that of China, are invaluable resources for the study and
      understanding of the process of plant domestication. Here, the considerable body
      of ancient Chinese literature is used to explore the domestication process that
      has occurred with the eggplant (Solanum melongena), an important vegetable in Old
      World. METHODS: Information about eggplant domestication in the ancient Chinese
      literature was retrieved using a variety of methods. The information obtained was
      then sorted by taxon, examined and taxonomic identifications verified. KEY
      RESULTS: It was found that the earliest record of the eggplant documented in
      ancient Chinese literature was in a work from 59 bc. As far as is known, this is
      the earliest reliable and accurately dated record of eggplant in cultivation. The
      analysis reveals that the process of domestication of the eggplant in China
      involved three principal aspects of fruit quality: size, shape and taste. These
      traits were actively and gradually selected; fruit size changed from small to
      large, taste changed from not palatable to what was termed at the time sweetish,
      and that over time, a wider variety of fruit shapes was cultivated. CONCLUSIONS:
      The results indicate that, in addition to data gleaned from archaeology and
      genetics, evidence as to changes in key traits occurring during the process of
      plant domestication and selective forces responsible for these changes can be
      traced through the ancient literature in some civilizations.

PMID- 18819951
TI  - The iron-regulated transporter, MbNRAMP1, isolated from Malus baccata is involved
      in Fe, Mn and Cd trafficking.
AB  - BACKGROUND AND AIMS: Iron deficiency is one of the most common nutritional
      disorders in plants, especially in fruit trees grown in calcareous soil. Malus
      baccata is widely used as an apple rootstock in north China and is highly
      resistant to low temperatures. There are few studies on iron absorption by this
      species at the molecular level. It is very important to understand the mechanism
      of iron uptake and transport in such woody plants. As a helpful tool, the aim of
      the present study was the cloning and functional analysis of NRAMP (natural
      resistance-associated macrophage protein) genes from the apple tree in relation
      to trafficking of micronutrients (Fe, Mn and Cd). METHODS: Reverse transcription
      PCR (RT-PCR) combined with RACE (rapid amplification of cDNA ends) was adopted to
      isolate the full-length NRAMP1 cDNA. Southern blotting was used to test gene copy
      information, and northern blot was used to detect the gene's expression level.
      Complementation experiments using the yeast mutant strains DEY1453 and SLY8 were
      employed to confirm the iron- and manganese-transporting ability of NRAMP1 from
      apple, and inductively coupled plasma (ICP) spectrometry was used to measure Cd
      accumulation in yeast. NRAMP1-green fluorescent protein (GFP) fusion protein was
      used to determine the cellular localization in yeast. KEY RESULTS: A 2090 bp cDNA
      was isolated and named MbNRAMP1. It encodes a predicted polypeptide of 551 amino
      acids. MbNRAMP1 exists in the M. baccata genome as a single copy and was
      expressed mainly in roots. MbNRAMP1 rescued the phenotype of yeast mutant strains
      DEY1453 and SLY8, and also increased Cd2+ sensitivity and accumulation. MbNRAMP1
      expression in yeast was largely influenced by iron status, and the expression
      pattern of MbNRAMP1-GFP varied with the environmental iron nutrition status.
      CONCLUSIONS: MbNRAMP1 encodes a functional metal transporter capable of mediating
      the distribution of ions as well as transport of the micronutrients, Fe and Mn,
      and the toxic metal, Cd.

PMID- 18819952
TI  - Measuring and interpreting respiratory critical oxygen pressures in roots.
AB  - BACKGROUND AND AIMS: Respiratory critical oxygen pressures (COPR) determined from
      O(2)-depletion rates in media bathing intact or excised roots are unreliable
      indicators of respiratory O(2)-dependency in O(2)-free media and wetlands. A
      mathematical model was used to help illustrate this, and more relevant
      polarographic methods for determining COPR in roots of intact plants are
      discussed. METHODS: Cortical [O(2)] near the root apex was monitored indirectly
      (pea seedlings) from radial oxygen losses (ROL) using sleeving Pt electrodes, or
      directly (maize) using microelectrodes; [O(2)] in the root was controlled by
      manipulating [O(2)] around the shoots. Mathematical modelling of radial diffusive
      and respiratory properties of roots used Michaelis-Menten enzyme kinetics. KEY
      RESULTS: Respiration declined only when the O(2) partial pressure (OPP) in the
      cortex of root tips fell below 0.5-4.5 kPa, values consistent with depressed
      respiration near the centre of the stele as confirmed by microelectrode
      measurements and mathematical modelling. Modelling predictions suggested that the
      OPP of a significant core at the centre of roots could be below the usual
      detection limits of O(2)-microelectrodes but still support some aerobic
      respiration. CONCLUSIONS: In O(2)-free media, as in wetlands, the COPR for roots
      is likely to be quite low, dependent upon the respiratory demands, dimensions and
      diffusion characteristics of the stele/stelar meristem and the enzyme kinetics of
      cytochrome oxidase. Roots of non-wetland plants may not differ greatly in their
      COPRs from those of wetland species. There is a possibility that trace amounts of
      O(2) may still be present in stelar 'anaerobic' cores where fermentation is
      induced at low cortical OPPs.

PMID- 18819953
TI  - What happened to the polypill?

PMID- 18819954
TI  - Emergency services lack coordination, says healthcare watchdog.

PMID- 18819955
TI  - Aboriginal children are still twice as likely to die as other young Australians.

PMID- 18819957
TI  - Operative management of tennis elbow: a quantitative review.
AB  - INTRODUCTION: The results of operative management of tennis elbow are varied, and
      the indications for surgery are not well codified. Many operative techniques are
      reported, but a clear consensus on whether a given surgical procedure is more
      effective over another is yet to be reached. METHODS: We conducted a MEDLINE,
      CINAHL and EMBASE search on all available scientific articles that reported the
      outcomes of surgery for lateral epicondylopathy. Keywords used were 'tennis
      elbow', 'lateral epicondylitis', 'lateral epicondylalgia', 'tendinopathy',
      'tendonitis' and 'tendon'. Subheadings used were 'surgery', 'outcomes',
      'pathology', 'physiology' and 'operation'. All relevant articles were retrieved.
      Each article was scored using the Coleman methodology score (CMS), a highly
      repeatable methodology score, by two independent reviewers, followed by data
      analysis. RESULTS: The mean CMS for the 45 studies identified was 43 +/- 9 (of a
      possible 100 points), with 'number of patients', 'type of study', 'outcome
      criteria and assessment' and 'subject selection process' being the major low
      scorers. Also, there was no improvement in the CMS, and hence study design, over
      the years (intra-class correlation coefficient = 0.45). DISCUSSION: There is a
      dearth of quality evidence available to be able to advocate one operative
      technique over another. CONCLUSION: We stress the need for well-designed
      adequately powered randomized controlled trials to be able to understand which of
      these operative techniques is really superior to the others.

PMID- 18819958
TI  - A clinical prediction rule for identifying patients with patellofemoral pain who
      are likely to benefit from foot orthoses: a preliminary determination.
AB  - OBJECTIVE: To develop a clinical prediction rule to identify patients with
      patellofemoral pain (PFP) who are more likely to benefit from foot orthoses.
      DESIGN: Posthoc analysis of one treatment arm of a randomised clinical trial.
      SETTING: Single-centre trial in a community setting in Brisbane, Australia.
      PARTICIPANTS: 42 participants (mean age 27.9 years) with a clinical diagnosis of
      PFP (median duration 36 months). INTERVENTIONS: Foot orthoses fitted by a
      physiotherapist. MAIN OUTCOME MEASURES: Five-point global improvement scale at 12
      week follow-up, dichotomised with marked improvement equalling success. RESULTS:
      Potential predictor variables identified by univariate analyses were age, height,
      pain severity, anterior knee pain scale score, functional index questionnaire
      score, foot morphometry (arch height ratio, mid-foot width difference from non
      weight bearing to weight bearing) and overall orthoses comfort. Parsimonious
      fitting of these variables to a model that explained success with orthoses
      identified the following: age (>25 years), height (<165 cm), worst pain visual
      analogue scale (<53.25 mm) and a difference in mid-foot width from non-weight
      bearing to weight bearing (>10.96 mm). The pretest success rate of 40% increased
      to 86% if the patient exhibited three of these variables (positive likelihood
      ratio 8.8; 95% CI 1.2 to 66.9). CONCLUSION: Post-hoc analysis identified age,
      height, pain severity and mid-foot morphometry as possible predictors of
      successful treatment of PFP with foot orthoses, thereby providing practitioners
      with information for prescribing foot orthoses in PFP and stimulating further
      research.

PMID- 18819959
TI  - The impact of urinary stress incontinence in young and middle-age women
      practising recreational sports activity: an epidemiological study.
AB  - OBJECTIVES: To evaluate the prevalence of urinary stress incontinence (USI) in
      menstruating women practising recreational sports activity, to detect specific
      sports with a stronger association with urinary incontinence (UI) and to evaluate
      risk factors possibly related to this condition. DESIGN: Epidemiological study.
      SETTING: Non-competitive sports organisations in the province of Varese, Italy.
      PARTICIPANTS: 679 women of fertile age, practising recreational sports activity.
      INTERVENTION: Anonymous questionnaire on UI. MAIN OUTCOME MEASUREMENTS: The
      questionnaire included questions about patients' general characteristics,
      occurrence of UI in relation to sport or daily general activities, time of onset
      of this condition, frequency of leakage episodes, correlation of incontinence
      with types of movements or sports, subjective impression of being limited on such
      occasions and/or necessity to modify the type of sport. RESULTS: UI was reported
      by 101 women (14.9%). Of these, 32 (31.7%) complained of UI only during sports
      activity, 48 (47.5%) only during daily life and 21 (20.8%) in both circumstances.
      Body mass index and parity were significantly associated with the risk of UI.
      Looking at the different sports activities, a higher rate of incontinence was
      found in women participating in basketball (16.6%), athletics (15%), and tennis
      or squash (11%). 10.4% of women abandoned their favourite sport, because of USI,
      and a further 20% limited the way they practised their favourite sport to reduce
      leakage episodes. CONCLUSIONS: Female UI affects a significant proportion of
      young women practising non-competitive sports activity; it can cause abandonment
      of the sport or limitation of its practice.

PMID- 18819960
TI  - Weight loss and mortality risk in patients with chronic heart failure in the
      candesartan in heart failure: assessment of reduction in mortality and morbidity
      (CHARM) programme.
AB  - AIMS: The curiosity that leanness is associated with poor survival in patients
      with chronic heart failure (CHF) needs further insight by investigating the
      impact of weight loss on prognosis in a large sample of patients across a broad
      spectrum of both reduced and preserved left ventricular (LV) systolic function.
      METHODS AND RESULTS: We investigated the change in weight over 6 months in 6933
      patients in the Candesartan in Heart failure: Reduction in Mortality and
      morbidity (CHARM) programme, and its association with subsequent mortality (1435
      deaths) over a median 32.9 months follow-up using Cox proportional hazard models
      to account for the impact of body mass index and other risk predictors. We then
      used time-updated Cox models to relate each patient's ongoing data on annual
      weight change to their mortality hazard. The percentage weight loss over 6 months
      had a highly significant monotonically increasing association with excess
      mortality, both for cardiovascular and for other causes of death. Patients with
      5% or greater weight loss in 6 months had over a 50% increase in hazard compared
      with those with stable weight. Weight loss carried a particularly high risk in
      patients who were already lean at study entry. Findings were similar in the
      presence of dependent oedema, preserved or reduced LV ejection fraction, and
      treatment with candesartan, although weight loss was significantly less common on
      candesartan. The time-updated analyses revealed an even stronger link between
      weight loss and short-term risk of dying, i.e. risk increased more than four-fold
      for patients whose last recorded annual weight loss exceeded 10%. Weight gain had
      a more modestly increased short-term mortality risk. Weight loss accelerates in
      the year prior to death. CONCLUSIONS: Weight loss and leanness are important
      predictors of poor prognosis in CHF. Being lean and losing weight is particularly
      bad. The detection of weight change, and particularly weight loss, should be
      considered as an adverse sign prompting further evaluation.

PMID- 18819961
TI  - Effects of aspirin dose on ischaemic events and bleeding after percutaneous
      coronary intervention: insights from the PCI-CURE study.
AB  - AIMS: In the setting of percutaneous coronary intervention (PCI), due to a
      paucity of data, the optimal dose of aspirin is uncertain. We evaluated the
      safety of different doses of aspirin after PCI. METHODS AND RESULTS: In the PCI
      CURE study, 2658 patients with acute coronary syndromes undergoing PCI were
      stratified into three aspirin dose groups >/=200 mg (high, n = 1064), 101-199 mg
      (moderate, n = 538), and </=100 mg (low, n = 1056). For efficacy, the moderate-
      (7.4%) and high-dose groups (8.6%) had similar rates of cardiovascular death,
      myocardial infarction, or stroke compared with the low-dose group (7.1%). For
      safety, major bleeding was increased with high-dose aspirin [3.9, 1.5, and 1.9%
      in the high-, moderate-, and low-dose groups; hazard ratio (HR) of high vs. low
      dose 2.05 (95% CI 1.20-3.50, P = 0.009]. The net adverse clinical events (death,
      MI, stroke, major bleeding) favoured low-over high-dose aspirin (8.4 vs. 11.0%,
      HR 1.31, 95% CI 1.00-1.73 P = 0.056). CONCLUSION: In this large observational
      analysis of patients undergoing PCI, low-dose aspirin appeared to be as effective
      as higher doses in preventing ischaemic events but was also associated with a
      lower rate of major bleeding and an improved net efficacy to safety balance.

PMID- 18819962
TI  - Quantitative assessment of endomyocardial biopsy in arrhythmogenic right
      ventricular cardiomyopathy/dysplasia: an in vitro validation of diagnostic
      criteria.
AB  - AIMS: To provide a standardized endomyocardial biopsy (EMB) protocol and
      diagnostic quantitative parameters for arrhythmogenic right ventricular
      cardiomyopathy/dysplasia (ARVC/D). The Task Force criteria for the in vivo
      diagnosis of ARVC/D include tissue characterization by EMB as a major criterion.
      METHODS AND RESULTS: EMBs were simulated in vitro with a Cordis bioptome in
      explanted hearts from six groups: diffuse (n = 10) and segmental (n = 10) ARVC/D,
      dilated cardiomyopathy (DC) (n = 10), controls (n = 10), adipositas cordis (n =
      10), elderly >80 years (n = 10). Sampling sites were the RV inferior
      subtricuspid, antero-apical, and mid-outflow tract (RVOT), the septum, and the
      left ventricle (LV). Histomorphometry was performed to evaluate the amount of
      myocardium and fibrous and fatty tissues. Myocyte diameters and abnormalities
      were also assessed. By selecting a 95% specificity, the ARVC/D diagnostic cut
      offs on cumulative RV EMB samples are myocardium <59%, fibrosis >31% and fat >22%
      (80, 50, and 50% sensitivity, respectively). By excluding elderly and obese
      people groups a lower cut-off for fat was found (>9%). A high variability between
      different RV sampling sites was observed; the antero-apical was the most
      informative region although fat at this level is non-specific. No useful
      diagnostic cut-off for fatty tissue was identified at the antero-apical and RVOT
      area. No significant difference was found for any tissue parameter either in
      septal or in LV EMB. Increased RV myocyte diameters and cytological changes were
      detected in ARVC/D and DC. CONCLUSION: The residual myocardium is the main
      diagnostic morphometric parameter in ARVC/D, whereas fat at the apex is non
      specific. Sensitivity and specificity vary according to the RV region. Target
      sampling of the triangle of dysplasia is required, although only a single region
      is often informative, emphasizing the usefulness of imaging-guided EMB. There is
      no diagnostic value of either septal or LV EMB. Cardiomyopathic changes of the
      myocytes also appear important for establishing a pathological diagnosis.

PMID- 18819963
TI  - Waiting time to pregnancy according to maternal birthweight and prepregnancy BMI.
AB  - BACKGROUND: An association between a woman's own birthweight and her fecundity
      has been suggested, but no empirical data have been published on the association
      between maternal birthweight and waiting time to pregnancy (TTP). METHODS: In the
      Danish National Birth Cohort (1996-2002), which is an ongoing study of 92 274
      women and their pregnancies, information about TTP and prepregnancy BMI was
      collected during pregnancy. At the 7-year follow-up of the children, 21 786
      mothers reported their own birthweight and whether they were born at term or
      preterm. The association between maternal birthweight and TTP is presented as
      adjusted odds ratios with 95% confidence intervals. RESULTS: Low maternal
      birthweight (< or =2500 g for term and < or =1500 g for preterm birth) was
      associated with an increased risk of TTP of >1 year [term: 1.2 (1.0-1.5);
      preterm: 1.8 (1.1-3.1)]. The latter association was strongest in women with a BMI
      < 25 kg/m(2) [2.6 (1.4-4.7)]. High maternal birthweight (>4500 g for term and
      >3500 g for preterm) was also associated with an increased risk of TTP of >1 year
      [1.5 (1.0-2.0) and 1.3 (0.7-2.4), respectively], especially in women with a BMI >
      or = 25 kg/m(2) [1.8 (1.1-3.1) and 2.5 (1.0-6.4), respectively]. CONCLUSIONS:
      High or low maternal birthweight was associated with TTP > 1 year. Longer waiting
      times in women with very low birthweight may reflect an effect of being born very
      preterm. Subfecundity may partly be programmed in foetal life by factors that
      cause or correlate with foetal growth.

PMID- 18819964
TI  - 'Gift without a price tag': altruism in anonymous semen donation.
AB  - Commercialization of human gametes is now legally prohibited in Canada under the
      Assisted Human Reproduction Act 2004, making semen donation in Canada altruistic
      and anonymous by law. Donors must be altruistically motivated to donate gametes
      without receiving monetary rewards. Globally speaking, Canada is neither the
      first nor the only country in the world that has legislation to support
      altruistic gamete donation. Other countries have advocated similar systems either
      through legislative changes or implementation of best practice models. This paper
      is a review of literature assessing the differences in donation behaviours under
      paid and altruistic donation models. It provides contextual information of the
      current semen donation situation in Canada, while drawing upon relevant
      literature and research data from other countries as references. The author also
      attempts to re-conceptualize the meanings of altruism through exploring the
      complex interplay between psycho-social and institutional factors in influencing
      donors' behaviours. Although there is a substantial amount of research studying
      the impacts on donor recruitment when payment is withdrawn, very few research
      studies are found that focus on exploring altruistic donor recruitment
      strategies. It is unrealistic to expect the altruistic donation culture to emerge
      spontaneously in Canada without any multi-level efforts to coordinate the
      recruitment strategies. Research programmes are greatly needed to generate
      empirical knowledge that can guide the development of altruistic donor
      recruitment models geared to the current socio-cultural environment and
      legislative framework in Canada. The findings will be invaluable when the
      legislation comes up for parliamentary review in the near future.

PMID- 18819965
TI  - A reduced oxygen tension (5%) is not beneficial for maintaining human embryonic
      stem cells in the undifferentiated state with short splitting intervals.
AB  - BACKGROUND: Human embryos grow naturally in vivo in lower oxygen (O(2)) tension
      environments than atmospheric O(2) tension. Therefore, human embryonic stem cells
      (hESC), a derivative of embryos, will likely grow more favorably in a reduced
      O(2) tension. This study aimed to compare the behavior of hESC under reduced O(2)
      tension (5%) versus normoxia (21%). METHODS: hESC lines were cultured in
      different O(2) tensions and then examined for morphology, apoptosis and gene
      expression profiles. RESULTS: hESC grown in 5% O(2) tension were not
      morphologically different from hESC grown in normoxia on day 7 of the first and
      fourth passages. However, after prolonged culture without splitting (10-14 days),
      hESC colonies were thinner and looked better morphologically in 5% O(2), but the
      cells proliferated more slowly and their sizes were larger. At most time points,
      the gene expression profiles in both O(2) tensions showed no major difference in
      representative stemness genes (Oct-3/4, Nanog and Cripto), differentiation genes
      (Desmin, Nestin, alpha-fetoprotein and GDF-9) and hypoxia-related genes (HIF
      1alpha and VEGF). A lower level of cyclin-D1 mRNA (suggestive of less Wnt pathway
      signaling on day 7 of the fourth passage) and a higher level of Desmin
      (suggestive of more differentiation to mesoderm, at day 7 of the first passage)
      were detected in 5% O(2). CONCLUSIONS: This study suggests that for routine
      culture of hESC with a short splitting interval (7 days), a low O(2) tension (5%
      O(2)) probably does not provide significant advantages over the standard 21% O(2)
      tension for the maintenance of an undifferentiated state by the criteria used in
      this study.

PMID- 18819966
TI  - Has the licensing of respiratory quinolones for adults and the 7-valent
      pneumococcal conjugate vaccine (PCV-7) for children had herd effects with respect
      to antimicrobial non-susceptibility in invasive Streptococcus pneumoniae?
AB  - OBJECTIVES: The aim of the study was to analyse the evolution of antibiotic non
      susceptibility in Spanish invasive Streptococcus pneumoniae after licensure of
      respiratory-quinolones for adults and 7-valent pneumococcal conjugate vaccine
      (PCV-7) for immunization of children. METHODS: All invasive pneumococci received
      in the Reference Laboratory (January 2000-August 2007; n = 12 957 isolates) were
      serotyped, and susceptibility to penicillin/erythromycin/levofloxacin was
      determined. Antibiotic consumption and PCV-7 doses/year were provided by IMS and
      the manufacturer, respectively. RESULTS: In 2000-07, PCV-7 distribution
      (doses/1000 inhabitants </=59 months age/year) increased from 0.0 to 411.90, and
      antibiotic consumption (DDD/1000 inhabitants/day) was maintained for beta-lactams
      ( approximately 16), decreased for macrolides (from 4.4 to 2.7) and increased for
      respiratory fluoroquinolones (from 0.3 to 2.7). The increase in PCV-7
      distribution correlated with a decrease in PCV-7 serotypes prevalence among
      invasive isolates in children (r = -0.976; P < 0.001) and adults (r = -0.905; P =
      0.002). This decrease in PCV-7 serotypes correlated with a decrease in penicillin
      non-susceptibility in children (r = 0.929; P < 0.001) and adults (r = 0.905; P =
      0.002) and with erythromycin non-susceptibility in children (r = 0.833; P =
      0.010). Penicillin/erythromycin non-susceptibility in 2000 was significantly
      higher in paediatric versus adult isolates (penicillin: 51.4% versus 29.2%;
      erythromycin: 39.5% versus 20.4%), but similar in 2006-07 (20% to 24%). The
      increase in respiratory quinolones consumption correlated with the increase in
      levofloxacin non-susceptibility in adults (r = 0.926; P = 0.008) but not in
      children, with different non-susceptibility rates in 2007 (1.6% versus 0.0%; P =
      0.013). CONCLUSIONS: This ecological analysis suggests that PCV-7 vaccination in
      children had a herd effect in adults, but consumption of respiratory quinolones
      in adults had no effect on pneumococcal susceptibility to levofloxacin in
      children. Penicillin/erythromycin non-susceptibility decreased along the studied
      period among paediatric invasive S. pneumoniae isolates to a level similar to
      that seen in adults.

PMID- 18819967
TI  - SmvA, and not AcrB, is the major efflux pump for acriflavine and related
      compounds in Salmonella enterica serovar Typhimurium.
AB  - OBJECTIVES: The aim was to study the role played by SmvA pump in the efflux of
      quaternary ammonium compounds (QACs) in Salmonella enterica serovar Typhimurium
      (Salmonella Typhimurium). METHODS: Mutants in the smvA, acrB and tolC genes were
      constructed by the red swap method. P22 was used to transduce tolC to acrB and
      smvA mutant strains. The susceptibility of these strains to acriflavine and a
      variety of QACs was determined by MIC assays. RESULTS: In comparison with the
      Salmonella Typhimurium wild-type strain, the smvA mutant was more susceptible to
      QACs than the acrB mutant strain. A tolC single mutant was more susceptible than
      an acrB mutant to QACs, acriflavine, ethidium bromide, malachite green and
      pyronin B. The tolC-acrB double mutant was as susceptible as the single tolC
      mutant to QACs. Additionally, the smvA mutant strain was more susceptible to
      acriflavine than the acrB mutant (MICs = 31.3 versus 125 mg/L, i.e. 4-fold).
      Finally, the tolC-smvA double mutant (3.9 mg/L) was approximately 10 times more
      susceptible to acriflavine than either smvA (31.3 mg/L) or tolC (31.3 mg/L)
      single mutants. CONCLUSIONS: It is the SmvA efflux pump, and not AcrB, that plays
      the major role in the efflux of acriflavine and other QACs from Salmonella
      Typhimurium. This apparently conflicting report is due to the fact that in
      Escherichia coli the smvA gene does not exist. Our results suggest that tolC and
      smvA genes encode components of two different efflux systems with overlapping
      specificities that work in parallel to export acriflavine and other QACs.

PMID- 18819968
TI  - Phase-dependent antifungal activity against Aspergillus fumigatus developing
      multicellular filamentous biofilms.
AB  - OBJECTIVES: Aspergillus fumigatus undergoes morphological transition throughout
      its growth and development. These changes have direct implications for the
      effectiveness of antifungal treatment. Here we report the in vitro antifungal
      activity of voriconazole, amphotericin B and caspofungin against three specific
      phases of multicellular development of A. fumigatus. METHODS: A. fumigatus
      conidia were propagated for 8, 12 and 24 h prior to antifungal challenge. The
      resultant activity of the three agents tested was determined using an XTT
      reduction assay to assess both endpoint and time-kill susceptibility profiles.
      RESULTS: Endpoint susceptibility testing demonstrated a time-dependent decrease
      in efficacy for all three antifungal agents as the complexity of the A. fumigatus
      hyphal structure developed. Overall, amphotericin B exhibited the best spectrum
      of activity at each phase of growth, but was comparable to voriconazole against
      germinated conidial growth (8 h). Later, both voriconazole and caspofungin were
      ineffective against complex mycelial structures (12 and 24 h). Time-kill studies
      demonstrated that amphotericin B was significantly more efficacious at reducing
      A. fumigatus metabolism than both voriconazole and caspofungin for all three
      growth phases examined, most notably after 1 h of drug exposure (P < 0.001).
      CONCLUSIONS: Overall, the data presented demonstrate that treatment of actively
      growing A. fumigatus cells with antifungal agents is more efficacious than
      treating mature structures in vitro. Amphotericin B was consistently more
      effective against each phase and displayed rapid effects, and therefore may be a
      suitable option for managing patient groups at risk from aspergillosis
      infections.

PMID- 18819969
TI  - The European Antibiotic Awareness Day.
AB  - The European Antibiotic Awareness Day, which will have as its theme the need to
      stop unnecessary use of antibiotics, will take place on 18 November 2008. It is
      hoped that healthcare workers and other professionals, particularly those
      involved with child care, as well the general public and members of the media,
      will participate in the various activities and discussions that will take place
      across Europe as part of this initiative. The European Antibiotic Awareness Day
      will be an annually recurring event that will raise awareness about the risks
      associated with inappropriate use of antibiotics and how to use antibiotics
      responsibly.

PMID- 18819970
TI  - Prevalence of antibiotic resistance in Campylobacter isolates from commercial
      poultry suppliers in KwaZulu-Natal, South Africa.
AB  - OBJECTIVES: Campylobacter jejuni isolated from broiler and layer chickens from
      registered abattoirs in KwaZulu-Natal, South Africa, were tested for their
      susceptibility to eight antibiotics. METHODS: Using agar dilution, susceptibility
      to eight antibiotics was determined for C. jejuni recovered from the caeca.
      RESULTS: A total of 155 isolates were collected of which 77 were identified as C.
      jejuni (broilers n = 56 and layers n = 21). Resistance was highest to
      tetracycline (broilers 98.2% and layers 100%) and ceftriaxone (broilers 96.4% and
      layers 100%). High susceptibility was found to ciprofloxacin (broilers 91% and
      layers 76%) and gentamicin (broilers 98% and layers 81%). Susceptibilities to
      each of the antibiotics for the broilers and layers, respectively, were: 50% and
      57% for erythromycin, 45% and 24% for clarithromycin, 68% and 43% for ampicillin
      and 64% and 48% for nalidixic acid. Statistically significant differences were
      detected for the MIC(50) of gentamicin, ciprofloxacin and tetracycline between
      broilers and layers (P < 0.001) with the MIC(90) of gentamicin also of
      significant difference (P = 0.01). Multiresistance was detected in 23% and 43% of
      the isolates from broiler and layer chickens, respectively. CONCLUSIONS: Mass
      therapy procedures used in animal husbandry have a potential impact on antibiotic
      resistance development in C. jejuni.

PMID- 18819971
TI  - Methicillin-resistant Staphylococcus aureus and animals: zoonosis or humanosis?
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) is increasing worldwide.
      Occasionally, animals are colonized or infected incidentally with human strains.
      Recently, however, new strains of MRSA emerging from within the animal kingdom,
      particularly in pigs, are causing human infection. MRSA has been reported in
      species as diverse as companion animals, horses and pigs, through to chinchillas,
      bats and parrots. In contrast, whereas strains of community-associated MRSA, the
      majority of which carry genes encoding Panton-Valentine leucocidin, are spreading
      rapidly in human populations, only sporadic cases have been reported in animals
      to date. Although MRSA has been found in some meat products, the implications for
      human infection through consumption are unclear. This review examines the
      epidemiology of MRSA in animals and human attendants/owners, the diagnosis and
      management of MRSA colonization, infection and infection control strategies in
      animals.

PMID- 18819972
TI  - New guidance from NICE regarding antibiotic prophylaxis for infective
      endocarditis--response by the BSAC working party.

PMID- 18819973
TI  - Detection of Pseudomonas aeruginosa isolates producing VEB-type extended-spectrum
      beta-lactamases in the United Kingdom.
AB  - OBJECTIVES: The aim of this study was to investigate the presence of VEB enzymes
      among Pseudomonas spp. referred to the UK's national reference laboratory and
      with phenotypic evidence of extended-spectrum beta-lactamase (ESBL) production.
      METHODS: Antibiograms were analysed for Pseudomonas spp. referred from November
      2003 to November 2007. Isolates with >/=4-fold ceftazidime/clavulanate synergy
      were screened for bla(VEB) alleles. Genes encoding metallo-beta-lactamases
      (bla(MBL)) were sought in isolates with positive imipenem/EDTA synergy tests.
      Selected PCR products were sequenced. PFGE of SpeI-digested genomic DNA was used
      to compare isolates. RESULTS: Forty-nine (3.7%) of 1338 Pseudomonas spp. were
      considered potential ESBL producers; 40 were recovered for molecular testing.
      bla(VEB) alleles were detected in 32 Pseudomonas aeruginosa isolates, comprising
      diverse PFGE types, from 12 UK hospitals and 1 in India. One UK centre referred
      15 isolates with VEB-1 enzyme; these were serotype O15, representing a single
      PFGE-defined strain that also produced VIM-10 metallo-carbapenemase. This strain
      was resistant to all beta-lactams, aminoglycosides and ciprofloxacin, remaining
      susceptible only to colistin (MICs </=1 mg/L). Two other P. aeruginosa isolates
      co-producing both VEB and VIM enzymes were received from two other UK hospitals;
      one isolate represented inter-hospital spread of the O15 strain and the second
      was distinct. CONCLUSIONS: VEB enzymes have not been reported previously in the
      UK, but were produced by 80% of Pseudomonas spp. with phenotypic evidence of ESBL
      production. They co-existed with VIM carbapenemases in two strains, with one
      responsible for a major hospital outbreak. The incidence of ESBLs may be
      underestimated in Pseudomonas because ESBL phenotypes can be masked by other beta
      lactam resistance mechanisms.

PMID- 18819974
TI  - In vitro activity of fusidic acid and mupirocin against coagulase-positive
      staphylococci from pets.
AB  - OBJECTIVES: Methicillin-resistant Staphylococcus aureus (MRSA) and multiresistant
      Staphylococcus pseudintermedius (MRSP) have emerged as important pathogens in
      animal infections. Associated therapeutic problems and the zoonotic potential of
      staphylococci have renewed interest in topical antibiotics for treatment and
      carrier decolonization. Fusidic acid and mupirocin are used topically in humans
      and animals but resistant strains isolated from people are increasing. This study
      investigates the in vitro activity of fusidic acid and mupirocin against
      coagulase-positive staphylococci from pets. METHODS: A collection of 287
      staphylococci was examined, comprising 102 MRSA, 102 methicillin-susceptible S.
      aureus, 71 S. pseudintermedius and 12 MRSP from canine and feline infections and
      carrier sites isolated in the UK and Germany. MICs were determined by the agar
      dilution method according to CLSI (formerly NCCLS) standards. RESULTS: The
      majority (89.7%) of all MICs were </=0.25 mg/L. High MICs were observed for seven
      MRSA isolates (five with an MIC of fusidic acid of 512 mg/L, one with an MIC of
      fusidic acid of 1024 mg/L and one with with an MIC of mupirocin of 16 mg/L). MICs
      of both antibiotics were </=2 mg/L for all MRSP. Infection isolates had higher
      MICs than those isolated from carriage sites for both antibiotics (P </= 0.001).
      CONCLUSIONS: In all but seven MRSA isolates, MICs were below the concentrations
      achievable experimentally at application sites suggesting therapeutic efficacy of
      both antibiotics in infections involving multiresistant staphylococci and for
      decolonization of carriers. However, the seven MRSA with high MICs, all of the
      dominant UK human hospital lineages, highlight the importance of monitoring
      treatment success as resistant strains may occur in animals.

PMID- 18819975
TI  - Clinical implications of antimicrobial resistance for therapy.
AB  - The last decade has seen a significant improvement in published evidence to show
      the clinical predictive value of phenotypic susceptibility testing with
      categorization of pathogens as 'susceptible' or 'resistant' based on clinical
      breakpoints. Most of the published data are based on retrospective or prospective
      observational clinical studies of patients treated with appropriate [pathogen(s)
      susceptible] or inappropriate [pathogen(s)-resistant] chemotherapy. Appropriate
      therapy has been shown to improve outcomes in infections occurring in hospitals,
      such as bloodstream infection (BSI) and pneumonia in the intensive care unit.
      Infections due to specific pathogens such as extended-spectrum beta-lactamase
      producing Enterobacteriaceae, Pseudomonas aeruginosa and Staphylococcus aureus
      also respond better to appropriate than inappropriate antibiotics. The situation
      with vancomycin-resistant enterococci is less clear, perhaps due to the increased
      importance of patient confounders. Streptococcus pneumoniae when causing acute
      pneumonia with or without BSI is a well-known exception to the predictive value
      of laboratory-defined resistance. Antibiotic resistance also impacts on outcomes
      in the community where the evidence is best for urinary tract infection. The
      clinical studies are compatible with the current pharmacokinetic/pharmacodynamic
      paradigm used to explain and predict antibacterial effects and therefore have a
      sound basis in antimicrobial science. These data underline the importance of well
      constructed epidemiological studies to determine the prevalence of antimicrobial
      resistance in clinical practice and the central place of laboratory-based
      susceptibility testing in dictating antimicrobial therapy and so optimizing
      patient outcomes.

PMID- 18819976
TI  - Survey, laboratory and statistical methods for the BSAC Resistance Surveillance
      Programmes.
AB  - OBJECTIVES: The British Society for Antimicrobial Chemotherapy (BSAC) Bacteraemia
      and Respiratory Resistance Surveillance Programmes are designed for long-term
      surveillance of antimicrobial resistance in key pathogens of bloodstream and
      community-acquired respiratory infection in the UK and Ireland. This paper
      describes their methods in detail. METHODS: Sentinel laboratories across the UK
      and Ireland contributed up to a fixed quota of isolates of defined bacterial
      groups. Collecting laboratories were compared with national benchmarks for size
      of Hospital Trust and distribution of bacteraemia pathogens. A central laboratory
      for each programme confirmed the identification of isolates, measured MICs by the
      BSAC agar dilution method and undertook further testing by standard methods. The
      variability of the MIC method was assessed by repeated annual testing of a panel
      of control isolates. Classification as susceptible, intermediate or resistant was
      by BSAC and European Committee on Antimicrobial Susceptibility Testing
      breakpoints. Statistical analysis was adjusted for inter-centre variation using
      random effects logistic regression. RESULTS: Thirty-two laboratories contributed
      16 550 respiratory isolates from 1999-2000 to 2006-07; 30 laboratories
      contributed 15 812 bacteraemia isolates from 2001 to 2006. Although large and
      teaching hospitals were over-represented, the pattern of bacteraemia organisms
      seen in the collecting laboratories in England and Wales was similar to that in
      national data reported to the Health Protection Agency. Replicate MIC
      measurements showed that >/=90% agreed within +/-1, and >/=98% within +/-2,
      doubling dilutions. CONCLUSIONS: These surveillance programmes have provided
      reliable information on antimicrobial susceptibility in the UK and Ireland over
      six and eight seasons, respectively, so far. Detailed results showing non
      susceptibility trends, and relationships with potential predictive factors, are
      presented in six linked papers in this Supplement.

PMID- 18819977
TI  - Analysis, power and design of antimicrobial resistance surveillance studies,
      taking account of inter-centre variation and turnover.
AB  - OBJECTIVES: Logistic regression is commonly used to analyse resistance
      surveillance studies, but variation between collecting centres undermines its
      assumption that isolates are independent. We studied the impact of this problem
      and the ability of alternative methods to overcome it. We also investigated
      different study designs and estimated the statistical power of the BSAC
      Resistance Surveillance Programmes. METHODS: We simulated datasets with various
      combinations of study design, inter-centre variation, annual centre turnover,
      initial resistance level and odds ratio, and analysed 1000 repetitions of each
      for trends in resistance by five variants of logistic regression. RESULTS:
      Traditional analysis by unadjusted logistic regression was invalid because it
      gave very high type 1 (false-positive) error rates, up to 49%, in the presence of
      high levels of inter-centre variation and turnover. Of the other methods
      investigated, logistic regression with random effects for centre performed best:
      it had appropriate error rates for all study designs assessed and generally had
      higher power than fixed-effects or cluster-robust approaches. A 'Diffuse' study
      with more centres contributing fewer isolates was less susceptible to the ill
      effects of inter-centre variation than a study of equal overall size with fewer
      centres contributing more, and had slightly higher power. CONCLUSIONS: Unadjusted
      logistic regression, ignoring inter-centre variation, is unsuitable for the
      analysis of trends in typical resistance surveillance studies, often leads to
      erroneous conclusions and should be avoided. Random effects logistic regression
      is an appropriate, widely applicable alternative, available in most standard
      statistical software. Collecting isolates from a larger number of centres has
      both statistical and scientific advantages.

PMID- 18819978
TI  - The British Society for Antimicrobial Chemotherapy Resistance Surveillance
      Project: a successful collaborative model.
AB  - The British Society for Antimicrobial Chemotherapy (BSAC) Resistance Surveillance
      Project was initiated in light of the need for UK-wide surveillance of
      antibacterial resistance in key clinical pathogens. The Project comprises two
      defined-protocol programmes that cover a range of important pathogens and
      antibacterials related to community-acquired respiratory tract infection and
      bloodstream infection, respectively. The Respiratory Programme has reported
      quantitative susceptibility data for Streptococcus pneumoniae, Haemophilus
      influenzae and Moraxella catarrhalis collected from across the UK and Ireland
      since 1999. The Bacteraemia Programme has reported the susceptibility of a wide
      range of Gram-positive and -negative organisms since 2001. The sustainability of
      the Programmes relies on a unique collaborative funding model: sponsorship is
      provided by a number of pharmaceutical companies in return for the inclusion of
      their investigational or marketed agents in the study alongside a core panel of
      established antibacterials. The sponsors have changed over time according to
      their interest in participating. Results for marketed agents are communicated in
      a timely manner through the BSAC web site and by presentation and publication,
      and for investigational agents with the agreement of their sponsors. The Project
      satisfies the requirement for sustainable defined-protocol high-quality
      resistance surveillance across the UK and Ireland.

PMID- 18819979
TI  - Non-susceptibility trends among Enterobacteriaceae from bacteraemias in the UK
      and Ireland, 2001-06.
AB  - BACKGROUND: Enterobacteriaceae are common agents of bacteraemia, with Escherichia
      coli accounting for 20% of the cases. Reflecting this importance, members of the
      family constitute 4 of the 12 collection groups in the British Society for
      Antimicrobial Chemotherapy (BSAC) Bacteraemia Surveillance Programme. METHODS:
      MICs from the BSAC surveillance programme were reviewed, along with bacteraemia
      reports received by the Health Protection Agency (HPA) via its CoSurv/LabBase
      system. Isolates with unusual resistances were subjected to molecular analysis.
      RESULTS: The BSAC and HPA systems both revealed dramatically increasing
      resistance to cephalosporins, ciprofloxacin and gentamicin among E. coli and
      Klebsiella spp., with cephalosporin resistance largely contingent on the spread
      of CTX-M extended-spectrum beta-lactamases (ESBLs); fluoroquinolone resistance
      also increased among Proteus mirabilis and ESBL-negative E. coli. Carbapenem
      resistance remained extremely rare, but two Enterobacter spp., from the same
      patient in different years, had KPC carbapenemases, while a few isolates had
      carbapenem resistance contingent upon combinations of beta-lactamase and
      impermeability, and ertapenem MICs for AmpC-derepressed Enterobacter spp. rose
      over time. Three new agents-ceftobiprole, doripenem and tigecycline-were tested.
      Ceftobiprole was broadly active, except against ESBL producers and Klebsiella
      oxytoca hyperproducing K1 enzyme, and was variable against AmpC-derepressed
      Enterobacter spp. and against Proteus vulgaris. Doripenem was more potent than
      imipenem. Tigecycline was almost universally active against E. coli, but low
      level non-susceptibility (MIC 2 mg/L) was frequent among Klebsiella spp.
      CONCLUSIONS: E. coli and Klebsiella spp. showed dramatic shifts, with sharply
      rising non-susceptibility to cephalosporins, ciprofloxacin and gentamicin. The
      rise in cephalosporin resistance reflected dissemination of CTX-M ESBLs.
      Carbapenems remain broadly active and new agents offer potential.

PMID- 18819980
TI  - Non-susceptibility trends among Pseudomonas aeruginosa and other non-fermentative
      Gram-negative bacteria from bacteraemias in the UK and Ireland, 2001-06.
AB  - BACKGROUND: Pseudomonas and Acinetobacter spp. are important opportunists,
      notorious for resistance. Pseudomonas spp. are collected in the British Society
      for Antimicrobial Chemotherapy (BSAC) bacteraemia surveillance, with
      Acinetobacter spp. and Stenotrophomonas maltophilia well represented in the
      'other Gram-negatives' group. METHODS: Data for collected isolates were reviewed
      together with LabBase bacteraemia reports to the Health Protection Agency (HPA).
      Isolates with unusual resistances were subjected to molecular investigation.
      RESULTS: From 2001 to 2006, the BSAC surveillance collected 1226 Pseudomonas
      aeruginosa, 240 Acinetobacter spp.-125 of them Acinetobacter
      calcoaceticus/baumannii (Acb) complex-and 165 S. maltophilia. Among P.
      aeruginosa, non-susceptibility rates to beta-lactams and gentamicin fluctuated,
      without trend, below 10%; those to ciprofloxacin ranged from 16% to 22%. One P.
      aeruginosa isolate from 2001 had VIM-2 metallo-beta-lactamase. For Acb, the BSAC
      data indicated frequent non-susceptibility, except to imipenem, where only five
      non-susceptible isolates were collected, all after 2003, four of them belonging
      to the OXA-23 clone 1 lineage which is prevalent in Southeast England. Reports to
      the HPA indicated rising imipenem non-susceptibility in Acb (P < 0.0001). Co
      trimoxazole retained near-universal activity against S. maltophilia. Among new
      antibiotics, doripenem MICs were </=4 mg/L for most imipenem-resistant P.
      aeruginosa but >/=16 mg/L for Acb OXA-23 clone 1. Ceftobiprole had higher MICs
      than ceftazidime for P. aeruginosa, but 81% of the isolates were inhibited at
      </=4 mg/L. Tigecycline had activity against most Acb, including OXA-23 clone 1,
      and also against S. maltophilia. CONCLUSIONS: Most P. aeruginosa from
      bacteraemias in the UK and Ireland remain relatively susceptible by international
      standards; in contrast, multiresistance is widespread in Acb, with imipenem non
      susceptibility emerging.

PMID- 18819981
TI  - Non-susceptibility trends among staphylococci from bacteraemias in the UK and
      Ireland, 2001-06.
AB  - OBJECTIVES: Investigation of the antibiotic susceptibilities and trends for
      staphylococci collected from bacteraemia cases in the UK and Ireland, from 2001
      to 2006, as part of the British Society for Antimicrobial Chemotherapy's
      Bacteraemia Surveillance Programme. METHODS: Twenty-five hospitals from the UK
      and Ireland each collected up to 10 consecutive isolates of both Staphylococcus
      aureus and coagulase-negative staphylococci (CoNS) per year from 2001 to 2006.
      MIC determination and identification to species level were carried out centrally.
      mecA and also mupA alleles were sought by PCR in S. aureus and CoNS from 2005 and
      2006, respectively. RESULTS: One thousand four hundred and forty-eight S. aureus
      and 1214 CoNS were collected. The overall prevalence of methicillin resistance
      was 42% (with </=6% annual fluctuation) for S. aureus and 67% (range 54% to 80%)
      for CoNS. Resistance to aminoglycosides, macrolides, quinolones and tetracyclines
      was strongly associated with methicillin resistance in both species groups. Many
      (20.8%) CoNS and three (0.2%) S. aureus isolates were non-susceptible to
      teicoplanin, but there was no vancomycin non-susceptibility found in S. aureus
      and only one vancomycin-intermediate CoNS isolate. There was little evidence of
      susceptibility trends over time for any antibiotic, with the surveillance period
      preceding the recent fall in methicillin-resistant S. aureus (MRSA) prevalence
      indicated by the mandatory surveillance of MRSA bacteraemia in England. The newer
      antibiotics, ceftobiprole, daptomycin, linezolid, telavancin and tigecycline, all
      had excellent activity against staphylococci. CONCLUSIONS: Multiresistant
      staphylococci remain abundant in the UK and Ireland but many new antimicrobials
      are becoming available and these may prove effective alternatives to
      glycopeptides.

PMID- 18819982
TI  - Non-susceptibility trends among enterococci and non-pneumococcal streptococci
      from bacteraemias in the UK and Ireland, 2001-06.
AB  - OBJECTIVES: To describe the current patterns and trends in antimicrobial
      susceptibility in enterococci and streptococci (excepting pneumococci) from
      bacteraemia in the UK and Ireland from 2001 to 2006. METHODS: In each year 2001
      06, blood culture isolates were collected by 25 laboratories distributed across
      the UK and Ireland. In total, there were 1408 isolates of enterococci, 1332 of
      beta-haemolytic streptococci and 1012 of alpha- and non-haemolytic streptococci.
      A single central laboratory re-identified the isolates and measured MICs by the
      BSAC agar dilution method. RESULTS: The prevalence of reduced susceptibility in
      streptococci and enterococci did not change significantly for most antibiotics,
      but trends were noted to increased ampicillin, imipenem and vancomycin resistance
      in Enterococcus faecium. The prevalence of reduced susceptibility to macrolides
      and tetracycline in streptococci, to tetracycline and gentamicin (high level) in
      enterococci and to beta-lactams and glycopeptides in E. faecium were all high,
      with some differences in the prevalence among species or groups. CONCLUSIONS:
      Reduced susceptibility to some antimicrobial agents among streptococci and
      enterococci remains common and continued surveillance is warranted.

PMID- 18819983
TI  - Non-susceptibility trends and serotype distributions among Streptococcus
      pneumoniae from community-acquired respiratory tract infections and from
      bacteraemias in the UK and Ireland, 1999 to 2007.
AB  - OBJECTIVES: Pneumococcal disease is prevalent and is a cause of significant
      morbidity and mortality in the UK and Ireland. We describe the antimicrobial
      susceptibility and serotype distributions of Streptococcus pneumoniae causing
      bacteraemia and community-acquired pneumonia in these countries from 1999/2000 to
      2006/7, predominantly prior to the introduction of the heptavalent pneumococcal
      conjugate vaccine (PCV7) into the standard vaccination schedule in September
      2006. METHODS: The BSAC Respiratory and Bacteraemia Resistance Surveillance
      Programmes collected S. pneumoniae from sentinel laboratories distributed across
      the UK and Ireland. A central laboratory for each programme re-identified the
      isolates, determined their serotypes and measured MICs by the BSAC agar dilution
      method. RESULTS: The prevalence of antimicrobial non-susceptibility, although
      significant, was generally below the global average. There was no convincing
      evidence of increasing non-susceptibility over time in either study. The results
      showed clear differences in the serotype distribution between respiratory and
      blood isolates, but suggested that PCV7 would provide adequate coverage of
      invasive isolates in the UK and Ireland. A significant and rapid increase of the
      non-vaccine serotype 1 among blood isolates from 2001 to 2006 was worrying, given
      the spread of hypervirulent serotype 1 clones elsewhere in the world.
      CONCLUSIONS: Continued surveillance of both antimicrobial non-susceptibility and
      serotype distribution changes following the introduction of PCV7 into the routine
      immunization schedule in the UK and Ireland is imperative. The data presented
      here, largely obtained prior to the introduction of PCV7 in the UK, provide a
      valuable baseline against which to monitor changes in antimicrobial non
      susceptibility and serotype distribution and hence to identify the expansion of
      any significant clones.

PMID- 18819984
TI  - Non-susceptibility trends among Haemophilus influenzae and Moraxella catarrhalis
      from community-acquired respiratory tract infections in the UK and Ireland, 1999
      2007.
AB  - OBJECTIVES: To determine the antimicrobial susceptibility of Haemophilus
      influenzae and Moraxella catarrhalis causing community-acquired respiratory tract
      infections in the UK and Ireland from 1999/2000 to 2006/07. METHODS: Sentinel
      laboratories across the UK and Ireland contributed up to a fixed quota of
      isolates of defined organisms per annum. A central laboratory confirmed the
      isolates' identities, measured MICs by the BSAC agar dilution method and
      undertook further testing by standard methods. The variability of the MIC method
      was assessed by repeated annual testing of control isolates. BSAC and EUCAST
      breakpoints were used. Statistical analysis adjusted for inter-centre variation
      by random effects logistic regression. RESULTS: A total of 7371 H. influenzae and
      2529 M. catarrhalis isolates were investigated. Over 90% of the H. influenzae
      isolates were susceptible to most of the antimicrobials tested, the exceptions
      being ampicillin (84.6% susceptible), trimethoprim (84.0%), cefuroxime (82.9%),
      amoxicillin (77.2%) and cefaclor (11.7%). For M. catarrhalis, resistance was
      solely due to beta-lactamase (prevalence over 91%) reducing susceptibility to
      penicillins only. There was little evidence of decreased antimicrobial
      susceptibility between 1999 and 2007 in either pathogen, except for a reduction
      in susceptibility to trimethoprim in H. influenzae (90.3% to 82.6%, P < 0.00001).
      On the other hand, tetracycline susceptibility in H. influenzae increased over
      this period in the UK and Ireland (96.5 to 98.8%, P = 0.00008). CONCLUSIONS:
      Despite increased resistance in respiratory pathogens from other parts of the
      world, the susceptibility of H. influenzae and M. catarrhalis to all agents,
      except tetracycline and trimethoprim in the case of H. influenzae, has remained
      constant during this longitudinal study.

PMID- 18819985
TI  - Thymidine kinase 2 defects can cause multi-tissue mtDNA depletion syndrome.
AB  - Mitochondrial DNA depletion syndrome (MDS) is a severe recessively inherited
      disease of childhood. It manifests most often in infancy, is rapidly progressive
      and leads to early death. MDS is caused by an increasing number of nuclear genes
      leading to multisystemic or tissue-specific decrease in mitochondrial DNA (mtDNA)
      copy number. Thymidine kinase 2 (TK2) has been reported to cause a myopathic form
      of MDS. We report here the clinical, autopsy and molecular genetic findings of
      rapidly progressive fatal infantile mitochondrial syndrome. All of our seven
      patients had rapidly progressive myopathy/encephalomyopathy, leading to
      respiratory failure within the first 3 years of life, with high creatine kinase
      values and dystrophic changes in the muscle with cytochrome c oxidase-negative
      fibres. In addition, two patients also had terminal-phase seizures, one had
      epilepsia partialis continua and one had cortical laminar necrosis. We identified
      two different homozygous or compound heterozygous mutations in the TK2 gene in
      all the patients: c.739 C s -> T and c.898 C -> T, leading to p.R172W and p.R225W
      changes at conserved protein sites. R172W mutation led to myopathy or
      encephalomyopathy with the onset during the first months of life, and was
      associated with severe mtDNA depletion in the muscle, brain and liver.
      Homozygosity for R225W mutation manifested during the second year of life as a
      myopathy, and showed muscle-specific mtDNA depletion. Both mutations originated
      from single ancient founders, with Finnish origin and enrichment for the new
      R172W mutation, and possibly Scandinavian ancestral origin for the R225W. We
      conclude that TK2 mutations may manifest as infantile-onset fatal myopathy with
      dystrophic features, but should be considered also in infantile progressive
      encephalomyopathy with wide-spread mtDNA depletion.

PMID- 18819986
TI  - Array analysis of epilepsy-associated gangliogliomas reveals expression patterns
      related to aberrant development of neuronal precursors.
AB  - Gangliogliomas, the most frequent neoplasms in patients with pharmacoresistant
      focal epilepsies, are characterized by histological combinations of glial and
      dysplastic neuronal elements, a highly differentiated phenotype and rare gene
      mutations. Their molecular basis and relationship to other low-grade brain
      tumours are not completely understood. Systematic investigations of altered gene
      expression in gangliogliomas have been hampered by their cellular complexity, the
      lack of suitable control tissue and of sensitive expression profiling approaches.
      Here, we have used discrete microdissected ganglioglioma and adjacent control
      brain tissue obtained from the neurosurgical access to the tumour of identical
      patients (n = 6) carefully matched for equivalent glial and neuronal elements in
      an amount sufficient for oligonucleotide microarray hybridization without
      repetitive amplification. Multivariate statistical analysis identified a rich
      profile of genes with altered expression in gangliogliomas. Many differentially
      expressed transcripts related to intra- and intercellular signalling including
      protein kinase C and its target NELL2 in identical ganglioglioma cell components
      as determined by real-time quantitative RT-PCR (qRT-PCR) and in situ
      hybridization. We observed the LIM-domain-binding 2 (LDB2) transcript, critical
      for brain development during embryogenesis, as one of the strongest reduced mRNAs
      in gangliogliomas. Subsequent qRT-PCR in dysembryoplastic neuroepithelial tumours
      (n = 7) revealed partial expression similarities as well as marked differences
      from gangliogliomas. The demonstrated gene expression profile differentiates
      gangliogliomas from other low-grade primary brain tumours. shRNA-mediated
      silencing of LDB2 resulted in substantially aberrant dendritic arborization in
      cultured developing primary hippocampal neurons. The present data characterize
      novel molecular mechanisms operating in gangliogliomas that contribute to the
      development of dysplastic neurons and an aberrant neuronal network.

PMID- 18819987
TI  - Role of microglial IKKbeta in kainic acid-induced hippocampal neuronal cell
      death.
AB  - Microglial cells are activated during excitotoxin-induced neurodegeneration.
      However, the in vivo role of microglia activation in neurodegeneration has not
      yet been fully elucidated. To this end, we used Ikkbeta conditional knockout mice
      (LysM-Cre/Ikkbeta(F/F)) in which the Ikkbeta gene is specifically deleted in
      cells of myeloid lineage, including microglia, in the CNS. This deletion reduced
      IkappaB kinase (IKK) activity in cultured primary microglia by up to 40% compared
      with wild-type (Ikkbeta(F/F)), and lipopolysaccharide-induced proinflammatory
      gene expression was also compromised. Kainic acid (KA)-induced hippocampal
      neuronal cell death was reduced by 30% in LysM-Cre/Ikkbeta(F/F) mice compared
      with wild-type mice. Reduced neuronal cell death was accompanied by decreased KA
      induced glial cell activation and subsequent expression of proinflammatory genes
      such as tumour necrosis factor (TNF)-alpha and interleukin (IL)-1beta. Similarly,
      neurons in organotypic hippocampal slice cultures (OHSCs) from LysM
      Cre/Ikkbeta(F/F) mouse brain were less susceptible to KA-induced excitotoxicity
      compared with wild-type OHSCs, due in part to decreased TNF-alpha and IL-1beta
      expression. Based on these data, we concluded that IKK/nuclear factor-kappaB
      dependent microglia activation contributes to KA-induced hippocampal neuronal
      cell death in vivo through induction of inflammatory mediators.

PMID- 18819988
TI  - Working memory performance is correlated with local brain morphology in the
      medial frontal and anterior cingulate cortex in fibromyalgia patients: structural
      correlates of pain-cognition interaction.
AB  - Fibromyalgia (FM) is a disorder of unknown aetiology, characterized by chronic
      widespread pain, stiffness and sleep disturbances. In addition, patients
      frequently complain of memory and attention deficits. Accumulating evidence
      suggests that FM is associated with CNS dysfunction and with an altered brain
      morphology. However, few studies have specifically investigated
      neuropsychological issues in patients suffering from FM. We therefore sought to
      determine whether neuropsychological deficits found in FM patients may be
      correlated with changes in local brain morphology specifically in the frontal,
      temporal or cingulate cortices. Twenty FM patients underwent extensive testing
      for potential neuropsychological deficits, which demonstrated significantly
      reduced working memory and impaired non-verbal long-term memory (limited to free
      recall condition) in comparison with normative data from age- and education
      matched control groups. Voxel-based morphometry (VBM) was used to evaluate for
      potential correlations between test results and local brain morphology.
      Performance on non-verbal working memory was positively correlated with grey
      matter values in the left dorsolateral prefrontal cortex, whereas performance on
      verbal working memory (digit backward) was positively correlated with grey matter
      values in the supplementary motor cortex. On the other hand, pain scores were
      negatively correlated with grey matter values in the medial frontal gyrus. White
      matter analyses revealed comparable correlations for verbal working memory and
      pain scores in the medial frontal and prefrontal cortex and in the anterior
      cingulate cortex. Our data suggest that, in addition to chronic pain, FM patients
      suffer from neurocognitive deficits that correlate with local brain morphology in
      the frontal lobe and anterior cingulate gyrus, which may be interpreted to
      indicate structural correlates of pain-cognition interaction.

PMID- 18819989
TI  - Acquisition of internal models of motor tasks in children with autism.
AB  - Children with autism exhibit a host of motor disorders including poor
      coordination, poor tool use and delayed learning of complex motor skills like
      riding a tricycle. Theory suggests that one of the crucial steps in motor
      learning is the ability to form internal models: to predict the sensory
      consequences of motor commands and learn from errors to improve performance on
      the next attempt. The cerebellum appears to be an important site for acquisition
      of internal models, and indeed the development of the cerebellum is abnormal in
      autism. Here, we examined autistic children on a range of tasks that required a
      change in the motor output in response to a change in the environment. We first
      considered a prism adaptation task in which the visual map of the environment was
      shifted. The children were asked to throw balls to visual targets with and
      without the prism goggles. We next considered a reaching task that required
      moving the handle of a novel tool (a robotic arm). The tool either imposed forces
      on the hand or displaced the cursor associated with the handle position. In all
      tasks, the children with autism adapted their motor output by forming a
      predictive internal model, as exhibited through after-effects. Surprisingly, the
      rates of acquisition and washout were indistinguishable from normally developing
      children. Therefore, the mechanisms of acquisition and adaptation of internal
      models in self-generated movements appeared normal in autism. Sparing of
      adaptation suggests that alternative mechanisms contribute to impaired motor
      skill development in autism. Furthermore, the findings may have therapeutic
      implications, highlighting a reliable mechanism by which children with autism can
      most effectively alter their behaviour.

PMID- 18819990
TI  - Auditory cortex asymmetry, altered minicolumn spacing and absence of ageing
      effects in schizophrenia.
AB  - The superior temporal gyrus, which contains the auditory cortex, including the
      planum temporale, is the most consistently altered neocortical structure in
      schizophrenia (Shenton ME, Dickey CC, Frumin M, McCarley RW. A review of MRI
      findings in schizophrenia. Schizophr Res 2001; 49: 1-52). Auditory hallucinations
      are associated with abnormalities in this region and activation in Heschl's
      gyrus. Our review of 34 MRI and 5 post-mortem studies of planum temporale reveals
      that half of those measuring region size reported a change in schizophrenia,
      usually consistent with a reduction in the left hemisphere and a relative
      increase in the right hemisphere. Furthermore, female subjects are under
      represented in the literature and insight from sex differences may be lost. Here
      we present evidence from post-mortem brain (N = 21 patients, compared with 17
      previously reported controls) that normal age-associated changes in planum
      temporale are not found in schizophrenia. These age-associated differences are
      reported in an adult population (age range 29-90 years) and were not found in the
      primary auditory cortex of Heschl's gyrus, indicating that they are selective to
      the more plastic regions of association cortex involved in cognition. Areas and
      volumes of Heschl's gyrus and planum temporale and the separation of the
      minicolumns that are held to be the structural units of the cerebral cortex were
      assessed in patients. Minicolumn distribution in planum temporale and Heschl's
      gyrus was assessed on Nissl-stained sections by semi-automated microscope image
      analysis. The cortical surface area of planum temporale in the left hemisphere
      (usually asymmetrically larger) was positively correlated with its constituent
      minicolumn spacing in patients and controls. Surface area asymmetry of planum
      temporale was reduced in patients with schizophrenia by a reduction in the left
      hemisphere (F = 7.7, df 1,32, P < 0.01). The relationship between cortical
      asymmetry and the connecting, interhemispheric callosal white matter was also
      investigated; minicolumn asymmetry of both Heschl's gyrus and planum temporale
      was correlated with axon number in the wrong subregions of the corpus callosum in
      patients. The spacing of minicolumns was altered in a sex-dependent manner due to
      the absence of age-related minicolumn thinning in schizophrenia. This is
      interpreted as a failure of adult neuroplasticity that maintains neuropil space.
      The arrested capacity to absorb anomalous events and cognitive demands may confer
      vulnerability to schizophrenic symptoms when adult neuroplastic demands are not
      met.

PMID- 18819991
TI  - Diffusion-weighted brain imaging study of patients with clinical diagnosis of
      corticobasal degeneration, progressive supranuclear palsy and Parkinson's
      disease.
AB  - Corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP) are two
      neurodegenerative disorders within the category of tauopathies, which must be
      considered in differential diagnosis of Parkinson's disease. Although specific
      clinical and neuroradiological features help to guide the clinician to a likely
      diagnosis of Parkinson's disease, CBD or PSP, differential diagnosis remains
      difficult. The aim of our study was to analyse apparent diffusion coefficient
      (ADC(ave)) maps from patients with clinical diagnosis of CBD (corticobasal
      syndrome, CBS), classical phenotype of PSP (Richardson's syndrome, RS) and
      Parkinson's disease (PD) in order to identify objective markers to discriminate
      between these groups. Thirteen Parkinson's disease patients, 10 RS patients, 7
      CBS patients and 9 healthy volunteers were recruited and studied in a 1.5 T MR
      scanner. Axial diffusion-weighted images were obtained and the ADC(ave) map was
      generated. Regions of interest (ROIs) included mesencephalon, corpus callosum and
      left and right superior cerebellar peduncle (SCP), thalamus, caudate, putamen,
      pallidus, posterior limb of internal capsule, frontal and parietal white matter.
      Histograms of ADC(ave) were generated for all voxels in left and right cerebral
      hemispheres and in left and right deep grey matter regions separately, and the
      50th percentile values (medians) were determined. The ratio of the smaller to the
      larger median value (symmetry ratio) was calculated for left and right
      hemispheres and for left and right deep grey matter regions (1 = perfect
      symmetry). Putaminal ADC(ave) values in CBS and RS were significantly greater
      than those in Parkinson's disease and healthy volunteers, but could not
      distinguish CBS from RS patients. In CBS patients, the values of the medians of
      cerebral hemispheres histograms were significantly higher than those in RS,
      Parkinson's disease and healthy volunteers, while the hemispheric symmetry ratio
      in CBS (0.968, range 0.952-0.976) was markedly reduced compared with RS (0.993,
      range 0.992-0.994), Parkinson's disease (0.991, range 0.988-0.993) and healthy
      controls (0.990, range 0.988-0.993). The hemispheric symmetry ratio
      differentiated CBS patients from RS and Parkinson's disease patients with a
      sensitivity and specificity of 100%. In RS patients, the ADC(ave) values of the
      SCPs were significantly greater than those in Parkinson's disease and healthy
      volunteers. Our findings confirm that putaminal ADC(ave) values evaluation
      provides a good discrimination between Parkinson's disease and atypical
      parkinsonisms, including RS and CBS. Furthermore, diffusion-weighted imaging, by
      detecting the brain microstructural correlates of the typical asymmetric signs
      and symptoms in CBS and the SCP involvement in RS, was shown to aid
      characterization and differentiation of atypical parkinsonism.

PMID- 18819992
TI  - Risk of subarachnoid haemorrhage according to number of affected relatives: a
      population based case-control study.
AB  - Relatives of patients with aneurysmal subarachnoid haemorrhage (SAH) have an
      increased risk of this type of stroke. In a population-based study, we analysed
      individualized risks of SAH according to the number of affected first-degree
      relatives. We retrieved all patients diagnosed with SAH in 2001-05 from the
      Swedish Inpatient Register. For each of the 5,282 patients, we identified five
      controls (n = 26,402) through the nationwide Register of Total Population.
      Through the Multi-generation Register, we retrieved all first-degree relatives
      for patients and controls and checked whether these 130,373 relatives had been
      diagnosed with SAH. By means of conditional logistic regression, we calculated
      odds ratios with corresponding 95% confidence intervals (95% CI) for the risk of
      SAH according to the number of affected relatives, and to the gender, age and
      type of kinship of the patient and affected relative. The odds ratio of SAH for
      individuals with one affected first-degree relative was 2.15 (95% CI 1.77-2.59).
      For individuals with two affected first-degree relatives, the odds ratio was 51.0
      (95% CI 8.56-1117). Gender, age and type of kinship did not influence the risk
      for individuals with one or more affected relatives. The risk of SAH is slightly
      increased in the cases with one, but strongly increased in cases with two or more
      affected first-degree relatives. The latter strongly increased risk corresponds
      to a considerable absolute life-time risk of SAH and underscores the need to
      consider screening for aneurysms in these individuals.

PMID- 18819993
TI  - Tumour vascular disrupting agents: combating treatment resistance.
AB  - A large group of tubulin-binding microtubule-depolymerizing agents act as tumour
      vascular disrupting agents (VDAs). Several members of this group are now in
      clinical trials in combination with conventional anticancer drugs and
      radiotherapy. Here we briefly update on the development of tubulin-binding
      combretastatins as VDAs, summarize what is known of their mechanisms of action
      and address issues relating to treatment resistance, using disodium
      combretastatin A-4 3-O-phosphate (CA-4-P) as an example. Characteristically, VDAs
      cause a rapid shutdown of blood flow to tumour tissue with much less effect in
      normal tissues. However, the tumour rim is relatively resistant to treatment.
      Hypoxia (or hypoxia reoxygenation) induces upregulation of genes associated with
      angiogenesis and drug resistance. It may be possible to take advantage of
      treatment-induced hypoxia by combining with drugs that are activated under
      hypoxic conditions. In summary, VDAs provide a novel approach to cancer
      treatment, which should effectively complement standard treatments, if treatment
      resistance is addressed by judicious combination treatment strategies.

PMID- 18819994
TI  - PARP inhibitors and cancer therapy - early results and potential applications.
AB  - Polyadenosine diphosphate-ribose polymerase (PARP) inhibitors are emerging as an
      exciting new class of agents for treating cancer. There is pre-clinical evidence
      for their use to potentiate both chemotherapeutic agents and radiotherapy, and
      also as single agents. This paper discusses the early clinical work published
      showing their use in combination with temozolomide in malignant melanoma, and in
      familial (BRCA-related) cancers.

PMID- 18819995
TI  - Inhibition of vascular endothelial growth factor signalling using cediranib
      (RECENTIN; AZD2171) enhances radiation response and causes substantial
      physiological changes in lung tumour xenografts.
AB  - A number of pre-clinical studies have suggested that blocking vascular
      endothelial growth factor (VEGF) signalling can be beneficial in combination with
      radiotherapy. This study investigated the effects of cediranib, a highly potent
      orally available inhibitor of VEGF receptor tyrosine kinase activity in
      combination with radiation in Calu-6 lung xenografts. In nude mice, Calu-6
      tumours were established and treatments initiated at a volume of 250 mm(3).
      Tumour-localized radiotherapy was given as three or five daily fractions of 2 Gy.
      Cediranib (3 mg kg(-1)) was administered 2 h prior to each fraction and continued
      post radiotherapy (concomitant regimen) or was initiated immediately after the
      completion of radiotherapy (sequential regimen). The endpoint was the time taken
      for tumour volume to quadruple (RTV4). Combined treatments resulted in a
      significantly enhanced growth delay compared with either modality alone. The
      therapeutic benefit was the same irrespective of the scheduling regimen. Tumour
      regression was observed post radiotherapy, which was associated with high levels
      of apoptosis and necrosis, and pronounced antivascular effects in histological
      samples. The amplified antivascular effect of cediranib when given after
      radiation suggests that pre-irradiated endothelium is sensitized to cediranib.
      Concomitant 5-day treatment with both cediranib and radiation reduced vessel
      density, perfusion and increased in tumour hypoxia. This was not associated with
      an acquired radioresistance suggesting that the maintenance of cediranib
      treatment post radiotherapy prevents the contribution of hypoxic cells to tumour
      regrowth. Collectively, these data support the contention that VEGFR inhibition
      can enhance radiation response in pre-clinical models and provide a rationale to
      develop cediranib in combination with radiotherapy in the clinical setting.

PMID- 18819996
TI  - Experimental treatment of neuroblastoma using [131I]meta-iodobenzylguanidine and
      topotecan in combination.
AB  - The radiopharmaceutical [(131)I]meta-iodobenzylguanidine ([(131)I]MIBG) and the
      topoisomerase I inhibitor topotecan are both effective as single-agent treatments
      of neuroblastoma. Our purpose was to assess the therapeutic potential of
      [(131)I]MIBG and topotecan in combination using SK-N-BE(2c) neuroblastoma cells
      and UVW/NAT glioma cells expressing the noradrenaline transporter transgene.
      Topotecan treatment was given (i) before, (ii) after or (iii) simultaneously with
      [(131)I]MIBG. DNA fragmentation was evaluated by comet assay and cell cycle
      redistribution was determined by fluorescence-activated cell sorting. Combination
      index analysis indicated that delivery schedules (ii) and (iii) were more
      effective than schedule (i) with respect to clonogenic cell kill. Similarly,
      significant DNA damage was observed following treatment schedules (ii) and (iii)
      (p <0.005), but not (i). Prior exposure to topotecan did not significantly
      enhance [(131)I]MIBG uptake in athymic mice bearing tumour xenografts. We
      conclude that the enhancement of the efficacy of [(131)I]MIBG by combining it
      with topotecan was the result of inhibition of DNA damage repair rather than an
      increase in expression of the noradrenaline transporter by tumour.

PMID- 18819997
TI  - Epidermal growth factor receptor-targeted therapy.
AB  - High epidermal growth factor receptor (EGFR) expression is a feature of human
      tumours and is an adverse prognostic factor for radiotherapy outcome. High
      expression is associated with benefit from accelerated radiotherapy in patients
      with head and neck squamous cell carcinoma. Anti-EGFR strategies potentiate the
      effects of radiotherapy and the inhibition of deoxyribonucleic acid repair
      appears to be important amongst a wide range of mechanisms, which include effects
      on angiogenesis, differentiation and the immunological response. There is
      considerable interest in exploring combined modality therapies involving
      radiation and EGFR antagonists for the curative treatment of cancer patients.
      Important issues in designing new trials are to investigate optimal scheduling
      and to establish biobanks to develop biomarkers for future patient selection.

PMID- 18819998
TI  - Gene therapy approaches to enhance bioreductive drug treatment.
AB  - Hypoxia, or a lack of oxygen, occurs in 50-60% of solid human tumours. Clinical
      studies have shown that the presence and extent of hypoxia in a tumour cannot be
      predicted by size or histopathological stage but it is predictive of a poor
      outcome following radiotherapy, chemotherapy and surgery. However, as a
      physiological feature of tumours, it can be exploited and researchers have
      developed many hypoxia-selective chemotherapies or bioreductive drugs that are in
      varying stages of clinical development. These agents are prodrugs that have two
      key requirements for their biological activation: they require the reductive
      environment of a hypoxic tumour cell and the appropriate complement of cellular
      reductase enzymes. To overcome tumour heterogeneity in reductase enzyme levels
      and enhance bioreductive drug metabolism a gene therapy strategy can be employed.
      We have reviewed this field and also present our own pre-clinical research using
      gene therapy to enhance bioreductive drug treatment for the treatment of cancer.
      We have specifically focused on studies enhancing lead clinical bioreductive
      drugs. We consider the metabolic requirements for their activation and we
      highlight the key in vivo studies supporting the future clinical development of
      hypoxia-targeted gene-directed enzyme prodrug therapy.

PMID- 18819999
TI  - The thioredoxin system: a key target in tumour and endothelial cells.
AB  - Thioredoxin is a redox-sensitive molecule that has pleiotropic cellular effects,
      such as the control of proliferation, redox states and apoptosis, and is often
      upregulated in malignancy. The system controls the activation of a number of
      transcription factors through sulphydryl transfer and, through its activity on
      hypoxia inducible factor 1alpha, it is able to regulate vascular endothelial
      growth factor levels and hence angiogenesis. The thioredoxin protein has been
      shown to be upregulated in hypoxic regions of certain tumours, suggesting that
      inhibitors could potentially exhibit enhanced hypoxic toxicity and/or indirect
      anti-angiogenic effects. Evidence of this is becoming apparent in the literature.
      The current report reviews the thioredoxin system as an anticancer drug target
      and focuses upon two recent compounds, PMX464 and PX12, which reportedly inhibit
      this important pathway.

PMID- 18820000
TI  - Exploiting the Achilles heel of cancer: the therapeutic potential of poly(ADP
      ribose) polymerase inhibitors in BRCA2-defective cancer.
AB  - Poly(ADP-ribose) polymerase-1 (PARP-1) facilitates DNA single-strand break-base
      excision repair to maintain genomic stability. Inhibition or loss of PARP
      activity leads to a recombinogenic phenotype characterized by increased sister
      chromatid exchange. Deficiency in homologous recombination (HR) owing to loss of
      BRCA1 or BRCA2 is associated with hereditary cancers of the breast, ovary,
      pancreas and prostate. We investigated the therapeutic potential of PARP
      inhibitors in HR and BRCA2-defective cells. We exposed cells defective in the HR
      component XRCC3 (irs1SF) and BRCA2 (V-C8) and their parental (AA8, V79) or
      deficiency corrected (CXR3, V-C8+B2) cells to the PARP inhibitors NU1025 and
      AG14361. Mice bearing BRCA2-deficient and BRCA2-proficient tumours were treated
      with AG14361. All HR-defective cells were hypersensitive to normally non
      cytotoxic concentrations of PARP inhibitors. Cells lacking BRCA2 were 20 times
      more sensitive to PARP inhibitor-induced cytotoxicity. Three out of five BRCA2
      defective xenografts responded to the potent PARP inhibitor, AG14361, and one
      tumour regressed completely, compared with non-responses in the BRCA2-proficient
      tumours treated with AG14361 or any mice treated with vehicle control. Untreated
      PARP-1(-/-) mouse embryo fibroblasts (MEFs) accumulated more DNA double-strand
      breaks than did PARP-1(+/+) MEFs. We believe the underlying cytotoxic mechanism
      is due to PARP inhibitor-mediated suppression of repair of DNA single-strand
      breaks, which are converted to DNA double-strand breaks at replication. These
      replication-associated double-strand breaks, which are normally repaired by HR,
      become cytotoxic in cells defective in HR. Using a DNA repair inhibitor alone to
      selectively kill a tumour represents an exciting new concept in cancer therapy.

PMID- 18820001
TI  - A proteomic approach to identifying new drug targets (potentiating topoisomerase
      II poisons).
AB  - Topoisomerase II poisons are an established part of best clinical practice for
      the treatment of a number of solid tumours and haematological malignancies.
      However, toxicity and resistance to chemotherapeutic drugs often complicate the
      treatment. Furthermore, topoisomerase II poisons can also induce sister chromatid
      exchange, chromosomal recombination and chromosome aberrations and are associated
      with a significant risk of secondary leukaemia. It would therefore be of great
      clinical benefit if the efficacy of topoisomerase II inhibitors could be enhanced
      without the increased toxic side effects. It is proposed that clinical agents
      targeting topoisomerase II can be enhanced by inhibiting proteins that modulate
      topoisomerase II. The aim is to identify proteins, that by the nature of their
      interaction with topoisomerase II, represent putative drug targets.

PMID- 18820002
TI  - Age-related analysis of insulin resistance, body weight and arterial pressure in
      the Zucker fatty rat.
AB  - The evolution with ageing of insulin resistance, body weight (BW) and mean
      arterial pressure (MAP) was studied in a group of Zucker fatty rats (ZFRs, n =
      22), between 7 and 16 weeks of age, compared with an age-matched control group of
      Zucker lean rats (ZLRs, n = 22). The minimal model of glucose kinetics was
      applied to estimate glucose effectiveness, S(G), and insulin sensitivity, S(I),
      from insulinaemia and glycaemia measured during a 70 min intravenous glucose
      tolerance test. No correlation was found between S(G) and age in both ZFR and ZLR
      groups. No significant changes in mean S(G) between the two groups indicated no
      alteration of glucose-mediated glucose disposal. Estimates of S(I) from
      individual ZFRs were independent of age and, on average, showed 83% reduction (P
      < 0.001) compared with the ZLR group. Despite the lack of alteration of S(I) with
      age, the ZFR group showed an age-related increase of MAP, which correlated with
      increasing BW (r = 0.71 and P < 0.001). These results support the hypothesis that
      in our ZFRs, as a suitable genetic model of obesity and hypertension, insulin
      resistance is fully established at the age of 7 weeks and remains practically
      unaltered until at least the sixteenth week. An age-related increase in arterial
      pressure, observed in this strain, relates more properly to increasing BW, rather
      than insulin resistance. Development of hypertension with increasing age and BW
      may result from an enhanced insulin-mediated activity of the sympathetic nervous
      system, as observed in our previously reported study.

PMID- 18820003
TI  - Myonuclear domain size and myosin isoform expression in muscle fibres from
      mammals representing a 100,000-fold difference in body size.
AB  - This comparative study of myonuclear domain (MND) size in mammalian species
      representing a 100,000-fold difference in body mass, ranging from 25 g to 2500
      kg, was undertaken to improve our understanding of myonuclear organization in
      skeletal muscle fibres. Myonuclear domain size was calculated from three
      dimensional reconstructions in a total of 235 single muscle fibre segments at a
      fixed sarcomere length. Irrespective of species, the largest MND size was
      observed in muscle fibres expressing fast myosin heavy chain (MyHC) isoforms, but
      in the two smallest mammalian species studied (mouse and rat), MND size was not
      larger in the fast-twitch fibres expressing the IIA MyHC isofom than in the slow
      twitch type I fibres. In the larger mammals, the type I fibres always had the
      smallest average MND size, but contrary to mouse and rat muscles, type IIA fibres
      had lower mitochondrial enzyme activities than type I fibres. Myonuclear domain
      size was highly dependent on body mass in the two muscle fibre types expressed in
      all species, i.e. types I and IIA. Myonuclear domain size increased in muscle
      fibres expressing both the beta/slow (type I; r = 0.84, P < 0.001) and the fast
      IIA MyHC isoform (r = 0.90; P < 0.001). Thus, MND size scales with body size and
      is highly dependent on muscle fibre type, independent of species. However, myosin
      isoform expression is not the sole protein determining MND size, and other
      protein systems, such as mitochondrial proteins, may be equally or more important
      determinants of MND size.

PMID- 18820004
TI  - Harvey Cushing and the regulation of blood pressure in giraffe, rat and man:
      introducing 'Cushing's mechanism'.
AB  - The fundamental mechanism that underlies essential hypertension is a high total
      peripheral resistance. We review here possible origins of high total peripheral
      resistance in physiologically hypertensive giraffes, spontaneously hypertensive
      rats and humans with essential hypertension. We propose that a common link could
      be reduced brainstem perfusion, as first suggested by Cushing in 1901. Any
      tendency towards reduction of cerebral blood flow to the cardiovascular control
      centres in rest and sleep will be prevented by activation of a response arising
      in the brainstem. The response will proportionately increase systemic blood
      pressure and return cerebral blood flow to a new homeostatic level. New evidence
      we review here supports this idea and leads us to suggest that central regulation
      of blood pressure has two components: the classic Cushing's response, which is a
      terminal event, and a Cushing's mechanism, which is a physiological mechanism for
      long-term control of mean arterial pressure. In giraffes, Cushing's mechanism is
      activated by increasing neck length during growth and subsequent gravitational
      hypotension that stimulates a rise in basal arterial blood pressure. In man and
      rats, the mechanism is activated by narrowing of the arteries supplying the
      brainstem. If we are correct, future successful treatment of essential
      hypertension in man will include methods of reducing cerebral arterial
      resistance.

PMID- 18820006
TI  - GnRH agonist therapy as ovarian protectants in female patients undergoing
      chemotherapy: a review of the clinical data.
AB  - BACKGROUND: Cancer survival rates in young women are improving due to progress in
      treatment. This includes aggressive chemotherapy, a treatment that often poses a
      threat to fertility. GnRH agonists were proposed as ovarian protectors during
      gonadotoxic therapies. This study was undertaken in order to determine the
      clinical evidence concerning this issue. METHODS: The medical literature was
      searched for studies that reported on ovarian function after the administration
      of GnRH agonists concomitant with chemotherapy. Twelve studies met the
      predetermined selection criteria. RESULTS: Data on ovarian function were obtained
      for 579 women who received chemotherapy. Among 345 women who received GnRH
      agonist co-treatment, ovarian function was preserved in 91% and 9% had premature
      ovarian failure. In 234 women who did not receive GnRH agonist co-treatment,
      ovarian function was preserved in 41% and failed in 59%. Only two of the studies
      were randomized. The control and the GnRH agonist groups differed in several
      important characteristics: the follow-up times were not equal, different
      treatment protocols were utilized and end-points were poorly defined and
      inconsistent between the studies. CONCLUSIONS: The effectiveness of GnRH agonists
      as fertility-preserving agents is debatable. A thorough literature search has
      found insufficient evidence to show that GnRH agonist co-treatment is effective
      in protecting the ovary from the damage of chemotherapy. A large randomized
      controlled trial with adequate follow-up is needed.

PMID- 18820007
TI  - LXR-induced reverse cholesterol transport in human airway smooth muscle is
      mediated exclusively by ABCA1.
AB  - The association of hypercholesterolemia and obesity with airway
      hyperresponsiveness has drawn increasing attention to the potential role of
      cholesterol and lipid homeostasis in lung physiology and in chronic pulmonary
      diseases such as asthma. We have recently shown that activation of the nuclear
      hormone receptor liver X receptor (LXR) stimulates cholesterol efflux in human
      airway smooth muscle (hASM) cells and induces expression of the ATP-binding
      cassette (ABC) transporters ABCA1 and ABCG1, members of a family of proteins that
      mediate reverse cholesterol and phospholipid transport. We show here that ABCA1
      is responsible for all LXR-mediated cholesterol and phospholipid efflux to both
      apolipoprotein AI and high-density lipoprotein acceptors. In contrast, ABCG1 does
      not appear to be required for this process. Moreover, we show that hASM cells
      respond to increased levels of cholesterol by inducing expression of ABCA1 and
      ABCG1 transporters, a process that is dependent on LXR expression. These findings
      establish a critical role for ABCA1 in reverse cholesterol and phospholipid
      transport in airway smooth muscle cells and suggest that dysregulation of
      cholesterol homeostasis in these cells may be important in the pathogenesis of
      diseases such as asthma.

PMID- 18820005
TI  - Infertility and the provision of infertility medical services in developing
      countries.
AB  - BACKGROUND: Worldwide more than 70 million couples suffer from infertility, the
      majority being residents of developing countries. Negative consequences of
      childlessness are experienced to a greater degree in developing countries when
      compared with Western societies. Bilateral tubal occlusion due to sexually
      transmitted diseases and pregnancy-related infections is the most common cause of
      infertility in developing countries, a condition that is potentially treatable
      with assisted reproductive technologies (ART). New reproductive technologies are
      either unavailable or very costly in developing countries. This review provides a
      comprehensive survey of all important papers on the issue of infertility in
      developing countries. METHODS: Medline, PubMed, Excerpta Medica and EMBASE
      searches identified relevant papers published between 1978 and 2007 and the
      keywords used were the combinations of 'affordable, assisted reproduction, ART,
      developing countries, health services, infertility, IVF, simplified methods,
      traditional health care'. RESULTS: The exact prevalence of infertility in
      developing countries is unknown due to a lack of registration and well-performed
      studies. On the other hand, the implementation of appropriate infertility
      treatment is currently not a main goal for most international non-profit
      organizations. Keystones in the successful implementation of infertility care in
      low-resource settings include simplification of diagnostic and ART procedures,
      minimizing the complication rate of interventions, providing training-courses for
      health-care workers and incorporating infertility treatment into sexual and
      reproductive health-care programmes. CONCLUSIONS: Although recognizing the
      importance of education and prevention, we believe that for the reasons of social
      justice, infertility treatment in developing countries requires greater attention
      at National and International levels.

PMID- 18820008
TI  - Long-term prognostic assessment of 185 newly diagnosed gliomas: Grade III glioma
      showed prognosis comparable to that of Grade II glioma.
AB  - OBJECTIVE: We evaluated the prognoses of newly diagnosed gliomas through WHO
      Grades II, III and IV to assess the overall tendency of treatment results for
      glioma in our institute. Furthermore, statistical analysis was performed to
      determine factors influencing the prognosis. METHODS: A total of 185 newly
      diagnosed glioma patients were operated on from 2000 to 2006. The primary
      endpoint was the overall survival from the date of surgery. The factors assessed
      as to whether they influenced the prognosis were the WHO grades of sex, age,
      location of the lesion, pre-operative Karnofsky Performance Status (KPS), extent
      of resection and whether or not radiation therapy was performed. RESULTS: The WHO
      grades influenced the survival significantly (P < 0.0001). The Grades II and III
      showed no statistically significant difference in survival (P = 0.174), whereas
      Grades III and IV showed a significant difference (P < 0.0001). The factor
      influencing survival as well as the grades was the KPS (P < 0.0001). The
      comparison of survival over WHO grades in the same KPS group was performed for 2
      KPS groups (KPS = 100, KPS 80-90), and these also showed significant differences
      (P = 0.0009 and 0.0143, respectively). CONCLUSIONS: Despite the different
      distributions of the KPS, the Grade III glioma patients showed survival
      comparable to that of the Grade II. On the other hand, the Grade IV glioma
      patients showed significantly poorer survival compared with Grade II or III.

PMID- 18820009
TI  - Possible difference in frequencies of genetic polymorphisms of estrogen receptor
      alpha, estrogen metabolism and P53 genes between estrogen receptor-positive and 
      negative breast cancers.
AB  - OBJECTIVE: Genetic polymorphisms associated with breast cancer risk are likely to
      differ among ethnic and molecular subtypes. The ability to identify genetic
      polymorphisms affecting the risk of estrogen receptor (ER)-positive breast cancer
      may lead to the more efficient selection of candidates for chemoprevention with
      endocrine agents. We focused on identifying common genotypes for ER-positive
      breast cancer in premenopausal Japanese women. METHODS: We compared genetic
      polymorphisms of ERalpha, estrogen metabolism genes (CYP17A1, CYP19A1, HSD17B1
      COASY, CYP1B1 and COMT), and p53 between ER-positive and -negative female
      Japanese breast cancer patients, and analyzed whether these polymorphisms
      affected the frequency of ER-positive breast cancer. RESULTS: Carriers of the G
      allele of ERalpha (rs6905370) were more frequent in ER-positive breast cancer
      than in ER-negative breast cancer especially in those under 50-year old. Pairwise
      analysis showed that combinations of the ERalpha G allele with the homozygous Trp
      genotype of CYP19A1 codon 39 (rs2236722), the methionine (Met) allele of COMT
      codon 158 (rs4680) or Pro allele of p53 codon 72 (rs1042522) were more frequent
      in ER-positive than ER-negative breast cancer, especially in patients less than
      50-year old. The frequencies of these combinations were even higher in patients
      with strongly ER-positive tumors (Allred's scores of 7 or 8). CONCLUSION: Our
      study demonstrated genetic polymorphisms of ERalpha, CYP19A1, COMT and p53 genes
      frequently occur in ER-positive breast cancer in premenopausal Japanese women.

PMID- 18820010
TI  - Chemotherapy for gastric cancer that recurs after adjuvant chemotherapy with S-1.
AB  - We retrospectively analyzed the efficacy of chemotherapy in patients whose
      gastric cancer recurred after adjuvant chemotherapy with S-1. A total of 51
      patients were evaluated. Twenty-one patients received S-1-containing chemotherapy
      as first-line treatment after recurrence [cohort A: S-1 plus cisplatin (n = 10),
      S-1 monotherapy (n = 7), S-1 plus irinotecan (n = 3) and S-1 plus docetaxel (n =
      1)]. The other 30 patients received a non-S-1-containing regimen [cohort B:
      paclitaxel or docetaxel (n = 22), irinotecan plus cisplatin (n = 6) and other
      drugs (n = 2)]. No objective responses occurred in cohort A, while five patients
      achieved a partial response in cohort B (response rate, 0 versus 16%; P = 0.04).
      Median progression-free survival was significantly longer in cohort B than in
      cohort A (4.3 versus 2.3 months, P = 0.02). S-1-containing chemotherapy does not
      appear to be effective in patients whose gastric cancer recurs after adjuvant S-1
      chemotherapy. Other chemotherapeutic agents should be evaluated in this setting.

PMID- 18820011
TI  - Right ventricular dilatation predicts survival after mitral valve repair in
      patients with impaired left ventricular systolic function.
AB  - AIMS: The prognostic value of the right ventricular parameters in patients with
      heart failure (HF) is well documented, but the data on patients undergoing mitral
      valve repair are lacking. METHODS AND RESULTS: The association between pre
      operative right ventricular dilatation and outcome was studied in 70 consecutive
      patients with HF who underwent elective mitral valve repair. Mean age was 67
      years, 71% were men, mean pre-operative NYHA class was 2.8, mean pre-operative
      ejection fraction was 31%, and 47% had atrial fibrillation. The ischaemic
      cardiomyopathy (ICM) was the cause of HF in 32% of the patients. Perioperative
      mortality was 7.1% by a median logistic Euroscore of 7.5 (range 1.3-47.5). During
      a mean follow-up of 887 days, 35% of the patients reached the combined endpoint
      of overall mortality or transplantation. Reoperation was performed in four
      patients. One and 3 years survival rates were 88% and 72%, respectively. By
      multivariate Cox analysis, right ventricular dilatation, ICM, and age
      significantly predicted the outcome. CONCLUSION: Right ventricular dilatation is
      an important modulator of outcome in patients with HF and mitral regurgitation.

PMID- 18820012
TI  - Frequent homologous recombination events in Mycobacterium tuberculosis PE/PPE
      multigene families: potential role in antigenic variability.
AB  - The PE and PPE (PE/PPE) multigene families of Mycobacterium tuberculosis are
      particularly GC-rich and share extensive homologous repetitive sequences. We
      hypothesized that they may undergo homologous recombination events, a mechanism
      rarely described in the natural evolution of mycobacteria. To test our
      hypothesis, we developed a specific oligonucleotide-based microarray targeting
      nearly all of the PE/PPE genes, aimed at detecting signals for homologous
      recombination. Such a microarray has never before been reported due to the
      multiplicity and highly repetitive and homologous nature of these sequences.
      Application of the microarray to a collection of M. tuberculosis clinical
      isolates (n = 33) representing prevalent spoligotype strain families in Tunisia
      allowed successful detection of six deleted genomic regions involving a total of
      two PE and seven PPE genes. Some of these deleted genes are known to be
      immunodominant or involved in virulence. The four precisely determined deletions
      were flanked by 400- to 500-bp stretches of nearly identical sequences lying
      mainly at the conserved N-terminal region of the PE/PPE genes. These highly
      homologous sequences thus serve as substrates to mediate both intergenic and
      intragenic homologous recombination events, indicating an important function in
      generating strain variation. Importantly, all recombination events yielded a new
      in-frame fusion chimeric gene. Hence, homologous recombination within and between
      PE/PPE genes likely increased their antigenic variability, which may have
      profound implications in pathogenicity and/or host adaptation. The finding of
      high prevalence (approximately 45% and approximately 58%) for at least two of the
      genomic deletions suggests that they likely confer advantageous biological
      attributes.

PMID- 18820013
TI  - Tricarboxylic acid cycle-dependent regulation of Staphylococcus epidermidis
      polysaccharide intercellular adhesin synthesis.
AB  - Staphylococcus epidermidis is a major nosocomial pathogen primarily infecting
      immunocompromised individuals or those with implanted biomaterials (e.g.,
      catheters). Biomaterial-associated infections often involve the formation of a
      biofilm on the surface of the medical device. In S. epidermidis, polysaccharide
      intercellular adhesin (PIA) is an important mediator of biofilm formation and
      pathogenesis. Synthesis of PIA is regulated by at least three DNA binding
      proteins (IcaR, SarA, and sigma(B)) and several environmental and nutritional
      conditions. Previously, we observed the environmental conditions that increased
      PIA synthesis decreased tricarboxylic acid (TCA) cycle activity. In this study,
      S. epidermidis TCA cycle mutants were constructed, and the function of central
      metabolism in PIA biosynthesis was examined. TCA cycle inactivation altered the
      metabolic status of S. epidermidis, resulting in a massive derepression of PIA
      biosynthetic genes and a redirection of carbon from growth into PIA biosynthesis.
      These data demonstrate that the bacterial metabolic status is a critical
      regulatory determinant of PIA synthesis. In addition, these data lead us to
      propose that the TCA cycle acts as a signal transduction pathway to translate
      external environmental cues into intracellular metabolic signals that modulate
      the activity of transcriptional regulators.

PMID- 18820014
TI  - Characterization of the oxygen-responsive NreABC regulon of Staphylococcus
      aureus.
AB  - Here, we investigate the functionality of the oxygen-responsive nitrogen
      regulation system NreABC in the human pathogen Staphylococcus aureus and evaluate
      its role in anaerobic gene regulation and virulence factor expression. Deletion
      of nreABC resulted in severe impairment of dissimilatory nitrate and nitrite
      reduction and led to a small-colony phenotype in the presence of nitrate during
      anaerobic growth. For characterization of the NreABC regulon, comparative DNA
      microarray and proteomic analyses between the wild type and nreABC mutant were
      performed under anoxic conditions in the absence and presence of nitrate. A
      reduced expression of virulence factors was not observed in the mutant. However,
      both the transcription of genes involved in nitrate and nitrite reduction and the
      accumulation of corresponding proteins were highly decreased in the nreABC
      mutant, which was unable to utilize nitrate as a respiratory oxidant and, hence,
      was forced to use fermentative pathways. These data were corroborated by the
      quantification of the extracellular metabolites lactate and acetate. Using an
      Escherichia coli-compatible two-plasmid system, the activation of the promoters
      of the nitrate and nitrite reductase operons and of the putative nitrate/nitrite
      transporter gene narK by NreBC was confirmed. Overall, our data indicate that
      NreABC is very likely a specific regulation system that is essential for the
      transcriptional activation of genes involved in dissimilatory reduction and
      transport of nitrate and nitrite. The study underscores the importance of NreABC
      as a fitness factor for S. aureus in anoxic environments.

PMID- 18820015
TI  - Dipeptidyl aminopeptidase IV from Stenotrophomonas maltophilia exhibits activity
      against a substrate containing a 4-hydroxyproline residue.
AB  - The crystal structure of dipeptidyl aminopeptidase IV from Stenotrophomonas
      maltophilia was determined at 2.8-A resolution by the multiple isomorphous
      replacement method, using platinum and selenomethionine derivatives. The crystals
      belong to space group P4(3)2(1)2, with unit cell parameters a = b = 105.9 A and c
      = 161.9 A. Dipeptidyl aminopeptidase IV is a homodimer, and the subunit structure
      is composed of two domains, namely, N-terminal beta-propeller and C-terminal
      catalytic domains. At the active site, a hydrophobic pocket to accommodate a
      proline residue of the substrate is conserved as well as those of mammalian
      enzymes. Stenotrophomonas dipeptidyl aminopeptidase IV exhibited activity toward
      a substrate containing a 4-hydroxyproline residue at the second position from the
      N terminus. In the Stenotrophomonas enzyme, one of the residues composing the
      hydrophobic pocket at the active site is changed to Asn611 from the corresponding
      residue of Tyr631 in the porcine enzyme, which showed very low activity against
      the substrate containing 4-hydroxyproline. The N611Y mutant enzyme was generated
      by site-directed mutagenesis. The activity of this mutant enzyme toward a
      substrate containing 4-hydroxyproline decreased to 30.6% of that of the wild-type
      enzyme. Accordingly, it was considered that Asn611 would be one of the major
      factors involved in the recognition of substrates containing 4-hydroxyproline.

PMID- 18820016
TI  - A two-component regulatory system integrates redox state and population density
      sensing in Pseudomonas putida.
AB  - A two-component system formed by a sensor histidine kinase and a response
      regulator has been identified as an element participating in cell density signal
      transduction in Pseudomonas putida KT2440. It is a homolog of the Pseudomonas
      aeruginosa RoxS/RoxR system, which in turn belongs to the RegA/RegB family,
      described in photosynthetic bacteria as a key regulatory element. In KT2440, the
      two components are encoded by PP_0887 (roxS) and PP_0888 (roxR), which are
      transcribed in a single unit. Characterization of this two-component system has
      revealed its implication in redox signaling and cytochrome oxidase activity, as
      well as in expression of the cell density-dependent gene ddcA, involved in
      bacterial colonization of plant surfaces. Whole-genome transcriptional analysis
      has been performed to define the P. putida RoxS/RoxR regulon. It includes genes
      involved in sugar and amino acid metabolism and the sulfur starvation response
      and elements of the respiratory chain (a cbb3 cytochrome oxidase, Fe-S clusters,
      and cytochrome c-related proteins) or genes participating in the maintenance of
      the redox balance. A putative RoxR recognition element containing a conserved
      hexamer (TGCCAG) has also been identified in promoters of genes regulated by this
      two-component system.

PMID- 18820017
TI  - Identification of a repressor of a truncated denitrification pathway in Moraxella
      catarrhalis.
AB  - Growth of Moraxella catarrhalis in a biofilm resulted in marked upregulation of
      two open reading frames (ORFs), aniA and norB, predicted to encode a nitrite
      reductase and a nitric oxide reductase, respectively (W. Wang, L. Reitzer, D. A.
      Rasko, M. M. Pearson, R. J. Blick, C. Laurence, and E. J. Hansen, Infect. Immun.
      75:4959-4971, 2007). An ORF designated nsrR, which was located between aniA and
      norB, was shown to encode a predicted transcriptional regulator. Inactivation of
      nsrR resulted in increased expression of aniA and norB in three different M.
      catarrhalis strains, as measured by both DNA microarray analysis and quantitative
      reverse transcriptase PCR. Provision of a wild-type nsrR gene in trans in an nsrR
      mutant resulted in decreased expression of the AniA protein. DNA microarray
      analysis revealed that two other ORFs (MC ORF 683 and MC ORF 1550) were also
      consistently upregulated in an nsrR mutant. Consumption of both nitrite and
      nitric oxide occurred more rapidly with cells of an nsrR mutant than with wild
      type cells. However, growth of nsrR mutants was completely inhibited by a low
      level of sodium nitrite. This inhibition of growth by nitrite was significantly
      reversed by introduction of an aniA mutation into the nsrR mutant and was
      completely reversed by the presence of a wild-type nsrR gene in trans. NsrR
      regulation of the expression of aniA was sensitive to nitrite, whereas NsrR
      regulation of norB was sensitive to nitric oxide.

PMID- 18820018
TI  - Genome sequence of a nephritogenic and highly transformable M49 strain of
      Streptococcus pyogenes.
AB  - The 1,815,783-bp genome of a serotype M49 strain of Streptococcus pyogenes (group
      A streptococcus [GAS]), strain NZ131, has been determined. This GAS strain (FCT
      type 3; emm pattern E), originally isolated from a case of acute post
      streptococcal glomerulonephritis, is unusually competent for
      electrotransformation and has been used extensively as a model organism for both
      basic genetic and pathogenesis investigations. As with the previously sequenced
      S. pyogenes genomes, three unique prophages are a major source of genetic
      diversity. Two clustered regularly interspaced short palindromic repeat (CRISPR)
      regions were present in the genome, providing genetic information on previous
      prophage encounters. A unique cluster of genes was found in the pathogenicity
      island-like emm region that included a novel Nudix hydrolase, and, further, this
      cluster appears to be specific for serotype M49 and M82 strains. Nudix hydrolases
      eliminate potentially hazardous materials or prevent the unbalanced accumulation
      of normal metabolites; in bacteria, these enzymes may play a role in host cell
      invasion. Since M49 S. pyogenes strains have been known to be associated with
      skin infections, the Nudix hydrolase and its associated genes may have a role in
      facilitating survival in an environment that is more variable and unpredictable
      than the uniform warmth and moisture of the throat. The genome of NZ131 continues
      to shed light upon the evolutionary history of this human pathogen. Apparent
      horizontal transfer of genetic material has led to the existence of highly
      variable virulence-associated regions that are marked by multiple rearrangements
      and genetic diversification while other regions, even those associated with
      virulence, vary little between genomes. The genome regions that encode surface
      gene products that will interact with host targets or aid in immune avoidance are
      the ones that display the most sequence diversity. Thus, while natural selection
      favors stability in much of the genome, it favors diversity in these regions.

PMID- 18820019
TI  - Nitric oxide and oxygen regulate truncated hemoglobin gene expression in Frankia
      strain CcI3.
AB  - The Frankia genome contains two truncated hemoglobin genes (hboN and hboO) whose
      functions remain to be determined. Nitric oxide (NO) generated by the addition of
      400 microM SNAP (S-nitroso-N-acetylpenicillamine) caused a 10-fold increase in
      hboN gene expression but had no effect on hboO expression. The addition of the NO
      scavenger, carboxy-PT10, reduced the effect of SNAP. hboO gene expression
      increased under low-oxygen conditions, while hboN expression was unaffected.
      These results suggest that HboN may function in protection from nitrosative
      stress and that HboO may act as an oxygen transport molecule for increased
      respiration in hypoxic environments.

PMID- 18820020
TI  - Processing of a membrane protein required for cell-to-cell signaling during
      endospore formation in Bacillus subtilis.
AB  - Activation of the late prespore-specific RNA polymerase sigma factor sigma(G)
      during Bacillus subtilis sporulation coincides with completion of the engulfment
      process, when the prespore becomes a protoplast fully surrounded by the mother
      cell cytoplasm and separated from it by a double membrane system. Activation of
      sigma(G) also requires expression of spoIIIJ, coding for a membrane protein
      translocase of the YidC/Oxa1p/Alb3 family, and of the mother cell-specific
      spoIIIA operon. Here we present genetic and biochemical evidence indicating that
      SpoIIIAE, the product of one of the spoIIIA cistrons, and SpoIIIJ interact in the
      membrane, thereby linking the function of the spoIIIJ and spoIIIA loci in the
      activation of sigma(G). We also show that SpoIIIAE has a functional Sec-type
      signal peptide, which is cleaved during sporulation. Furthermore, mutations that
      reduce or eliminate processing of the SpoIIIAE signal peptide arrest sporulation
      following engulfment completion and prevent activation of sigma(G). SpoIIIJ-type
      proteins can function in cooperation with or independently of the Sec system. In
      one model, SpoIIIJ interacts with SpoIIIAE in the context of the Sec translocon
      to promote its correct localization and/or topology in the membrane, so that it
      can signal the activation of sigma(G) following engulfment completion.

PMID- 18820021
TI  - Suppression of DeltabipA phenotypes in Escherichia coli by abolishment of
      pseudouridylation at specific sites on the 23S rRNA.
AB  - The BipA protein of Escherichia coli has intriguing similarities to the
      elongation factor subfamily of GTPases, including EF-Tu, EF-G, and LepA. In
      addition, phenotypes of a bipA deletion mutant suggest that BipA is involved in
      regulation of a variety of pathways. These two points have led to speculation
      that BipA may be a novel regulatory protein that affects efficient translation of
      target genes through direct interaction with the ribosome. We isolated and
      characterized suppressors of the cold-sensitive growth phenotype exhibited by
      DeltabipA strains and identified insertion mutations in rluC. The rluC gene
      encodes a pseudouridine synthase responsible for pseudouridine modification of
      23S rRNA at three sites, all located near the peptidyl transferase center.
      Deletion of rluC not only suppressed cold sensitivity but also alleviated the
      decrease in capsule synthesis exhibited by bipA mutants, suggesting that the
      phenotypic effects of BipA are manifested through an effect on the ribosome. The
      suppressor effect is specific to rluC, as deletion of other rlu genes did not
      relieve cold sensitivity, and further, more than a single pseudouridine residue
      is involved, as alteration of single residues did not produce suppressors. These
      results are consistent with a role for BipA in either the structure or the
      function of the ribosome and imply that wild-type ribosomes are dependent on BipA
      for efficient expression of target mRNAs and that the lack of pseudouridylation
      at these three sites renders the ribosomes BipA independent.

PMID- 18820022
TI  - Phenotypic and transcriptomic characterization of Bacillus subtilis mutants with
      grossly altered membrane composition.
AB  - The Bacillus subtilis membrane contains diacylglycerol-based lipids with at least
      five distinct headgroups that together help to define the physical and chemical
      properties of the lipid bilayer. Here, we describe the phenotypic
      characterization of mutant strains lacking one or more of the following lipids:
      glycolipids (ugtP mutants), phosphatidylethanolamine (pssA and psd mutants),
      lysylphosphatidylglycerol (mprF), and cardiolipin (ywnE and ywjE). Alterations of
      membrane lipid headgroup composition are generally well-tolerated by the cell,
      and even severe alterations lead to only modest effects on growth proficiency.
      Mutants with decreased levels of positively charged lipids display an increased
      sensitivity to cationic antimicrobial compounds, and cells lacking glycolipids
      are more sensitive to the peptide antibiotic sublancin and are defective in
      swarming motility. A quadruple mutant strain (ugtP pssA mprF ywnE), with a
      membrane comprised predominantly of phosphatidylglycerol, is viable and grows at
      near-wild-type rates, although it forms long, coiled filaments. Transcriptome
      comparisons identified numerous regulons with altered expression in cells of the
      ugtP mutant, the pssA mprF ywnE triple mutant, and the ugtP pssA mprF ywnE
      quadruple mutant. These effects included a general decrease in expression of the
      SigD and FapR regulons and increased expression of cell envelope stress responses
      mediated by sigma(M) and the YvrGHb two-component system.

PMID- 18820023
TI  - Maintenance role of a glutathionyl-hydroquinone lyase (PcpF) in pentachlorophenol
      degradation by Sphingobium chlorophenolicum ATCC 39723.
AB  - Pentachlorophenol (PCP) is a toxic pollutant. Its biodegradation has been
      extensively studied in Sphingobium chlorophenolicum ATCC 39723. All enzymes
      required to convert PCP to a common metabolic intermediate before entering the
      tricarboxylic acid cycle have been characterized. One of the enzymes is
      tetrachloro-p-hydroquinone (TeCH) reductive dehalogenase (PcpC), which is a
      glutathione (GSH) S-transferase (GST). PcpC catalyzes the GSH-dependent
      conversion of TeCH to trichloro-p-hydroquinone (TriCH) and then to dichloro-p
      hydroquinone (DiCH) in the PCP degradation pathway. PcpC is susceptible to
      oxidative damage, and the damaged PcpC produces glutathionyl (GS) conjugates, GS
      TriCH and GS-DiCH, which cannot be further metabolized by PcpC. The fate and
      effect of GS-hydroquinone conjugates were unknown. A putative GST gene (pcpF) is
      located next to pcpC on the bacterial chromosome. The pcpF gene was cloned, and
      the recombinant PcpF was purified. The purified PcpF was able to convert GS-TriCH
      and GS-DiCH conjugates to TriCH and DiCH, respectively. The GS-hydroquinone lyase
      reactions catalyzed by PcpF are rather unusual for a GST. The disruption of pcpF
      in S. chlorophenolicum made the mutant lose the GS-hydroquinone lyase activities
      in the cell extracts. The mutant became more sensitive to PCP toxicity and had a
      significantly decreased PCP degradation rate, likely due to the accumulation of
      the GS-hydroquinone conjugates inside the cell. Thus, PcpF played a maintenance
      role in PCP degradation and converted the GS-hydroquinone conjugates back to the
      intermediates of the PCP degradation pathway.

PMID- 18820024
TI  - Comparative genomics of regulation of fatty acid and branched-chain amino acid
      utilization in proteobacteria.
AB  - Bacteria can use branched-chain amino acids (ILV, i.e., isoleucine, leucine,
      valine) and fatty acids (FAs) as sole carbon and energy sources converting ILV
      into acetyl-coenzyme A (CoA), propanoyl-CoA, and propionyl-CoA, respectively. In
      this work, we used the comparative genomic approach to identify candidate
      transcriptional factors and DNA motifs that control ILV and FA utilization
      pathways in proteobacteria. The metabolic regulons were characterized based on
      the identification and comparison of candidate transcription factor binding sites
      in groups of phylogenetically related genomes. The reconstructed ILV/FA
      regulatory network demonstrates considerable variability and involves six
      transcriptional factors from the MerR, TetR, and GntR families binding to 11
      distinct DNA motifs. The ILV degradation genes in gamma- and betaproteobacteria
      are regulated mainly by a novel regulator from the MerR family (e.g., LiuR in
      Pseudomonas aeruginosa) (40 species); in addition, the TetR-type regulator LiuQ
      was identified in some betaproteobacteria (eight species). Besides the core set
      of ILV utilization genes, the LiuR regulon in some lineages is expanded to
      include genes from other metabolic pathways, such as the glyoxylate shunt and
      glutamate synthase in Shewanella species. The FA degradation genes are controlled
      by four regulators including FadR in gammaproteobacteria (34 species), PsrA in
      gamma- and betaproteobacteria (45 species), FadP in betaproteobacteria (14
      species), and LiuR orthologs in alphaproteobacteria (22 species). The remarkable
      variability of the regulatory systems associated with the FA degradation pathway
      is discussed from functional and evolutionary points of view.

PMID- 18820025
TI  - The RNA-binding domain of bacteriophage P22 N protein is highly mutable, and a
      single mutation relaxes specificity toward lambda.
AB  - Antitermination in bacteriophage P22, a lambdoid phage, uses the arginine-rich
      domain of the N protein to recognize boxB RNAs in the nut site of two regulated
      transcripts. Using an antitermination reporter system, we screened libraries in
      which each nonconserved residue in the RNA-binding domain of P22 N was
      randomized. Mutants were assayed for the ability to complement N-deficient virus
      and for antitermination with P22 boxB(left) and boxB(right) reporters. Single
      amino acid substitutions complementing P22 N(-) virus were found at 12 of the 13
      positions examined. We found evidence for defined structural roles for seven
      nonconserved residues, which was generally compatible with the nuclear magnetic
      resonance model. Interestingly, a histidine can be replaced by any other aromatic
      residue, although no planar partner is obvious. Few single substitutions showed
      bias between boxB(left) and boxB(right), suggesting that the two RNAs impose
      similar constraints on genetic drift. A separate library comprising only hybrids
      of the RNA-binding domains of P22, lambda, and phi21 N proteins produced mutants
      that displayed bias. P22 N(-) plaque size plotted against boxB(left) and
      boxB(right) reporter activities suggests that lytic viral fitness depends on
      balanced antitermination. A few N proteins were able to complement both lambda N-
      and P22 N-deficient viruses, but no proteins were found to complement both P22 N-
      and phi21 N-deficient viruses. A single tryptophan substitution allowed P22 N to
      complement both P22 and lambda N(-). The existence of relaxed-specificity mutants
      suggests that conformational plasticity provides evolutionary transitions between
      distinct modes of RNA-protein recognition.

PMID- 18820026
TI  - Ranolazine combined with enalapril or metoprolol prevents progressive LV
      dysfunction and remodeling in dogs with moderate heart failure.
AB  - Acute intravenous infusion of ranolazine (Ran), an anti-ischemic/antiangina drug,
      was previously shown to improve left ventricular (LV) ejection fraction (EF)
      without a concomitant increase in myocardial oxygen consumption in dogs with
      chronic heart failure (HF). This study examined the effects of treatment with Ran
      alone and in combination with metoprolol (Met) or enalapril (Ena) on LV function
      and remodeling in dogs with HF. Dogs (n = 28) with microembolization-induced HF
      were randomized to 3 mo oral treatment with Ran alone [375 mg twice daily (bid);
      n = 7], Ran (375 mg bid) in combination with Met tartrate (25 mg bid; n = 7), Ran
      (375 mg bid) in combination with Ena (10 mg bid; n = 7), or placebo (PL; Ran
      vehicle bid; n = 7). Ventriculographic measurements of LV end-diastolic volume
      (EDV) and end-systolic volume (ESV) and LV EF were obtained before treatment and
      after 3 mo of treatment. In PL-treated dogs, EDV and ESV increased significantly.
      Ran alone prevented the increase in EDV and ESV seen in the PL group and
      significantly increased EF, albeit modestly, from 35 +/- 1% to 37 +/- 2%. When
      combined with either Ena or Met, Ran prevented the increase in EDV, significantly
      decreased ESV, and markedly increased EF compared with those of PL. EF increased
      from 35 +/- 1% to 40 +/- 1% with Ran + Ena and from 34 +/- 1% to 41 +/- 1% with
      Ran + Met. Ran alone or in combination with Ena or Met was also associated with
      beneficial effects at the cellular level on histomorphometric parameters such as
      hypertrophy, fibrosis, and capillary density as well as the expression for
      pathological hypertrophy and Ca2+ cycling genes. In conclusion, Ran prevented
      progressive LV dysfunction and global and cellular myocardial remodeling, and Ran
      in combination with Ena or Met improved LV function beyond that observed with Ran
      alone.

PMID- 18820027
TI  - High glucose increases the expression of Gq/11alpha and PLC-beta proteins and
      associated signaling in vascular smooth muscle cells.
AB  - The levels and activity of protein kinase C and diacylglycerol were shown to be
      upregulated in diabetes/hyperglycemia; however, studies on the expression of
      upstream signaling molecules of phosphatidylinositol turnover were lacking. The
      present study was therefore undertaken to examine whether hyperglycemia/diabetes
      could also modulate the expression of Gqalpha and phospholipase C-beta (PLC-beta)
      proteins and associated phosphatidylinositol turnover signaling in aortic
      vascular smooth muscle cells (VSMCs) and A10 VSMCs exposed to high glucose.
      Aortic VSMCs from streptozotocin-diabetic rats exhibited an increased expression
      of Gqalpha and PLC-beta1 proteins (60% and 30%, respectively) compared with
      control cells as determined by Western blot analysis. The pretreatment of A10
      VSMCs with high glucose (26 mM) for 3 days also augmented the levels of Gqalpha,
      G11alpha, PLC-beta1 and -beta2 proteins by about 50, 35, 30, and 30%,
      respectively, compared with control cells that were restored to control levels by
      endothelin-1 (ET-1), ET types A and B (ET(A) and ET(B)) receptors, and
      angiotensin II type 1 (AT1) receptor antagonists. In addition, ET-1-stimulated
      inositol triphosphate formation was also significantly higher in VSMCs exposed to
      high glucose, whereas the basal levels of inositol triphosphate were not
      different between the two groups. Furthermore, the treatment of A10 VSMCs with
      angiotensin II and ET-1 also significantly increased the levels of Gq/11alpha and
      PLC-beta proteins that were restored toward control levels by ET(A)/ET(B) and AT1
      receptor antagonists. These results suggest that high glucose augments the
      expression of Gq/11alpha, PLC-beta, and mediated signaling in VSMCs, which may be
      attributed to AT1, ET(A), and ET(B) receptors.

PMID- 18820028
TI  - Aging and prostacyclin responses in aorta and platelets from WKY and SHR rats.
AB  - In spontaneously hypertensive rat (SHR) aorta, prostacyclin is an endothelium
      derived contracting factor contributing to the endothelial dysfunction. This
      study was designed to determine whether the impairment of the prostacyclin
      response is influenced by aging and whether such a dysfunction is observed in
      platelets. Isometric tension was measured in aortic rings, and aggregation was
      studied in platelet-rich plasma taken from 3-, 6-, and 15-mo-old Wistar-Kyoto
      rats (WKY) and SHR. In aorta from 3- and 6-mo-old WKY, prostacyclin and beraprost
      [prostacyclin receptor (IP) agonists] produced relaxations that were enhanced by
      Triplion (thromboxane-prostanoid receptor antagonist). In 15-mo-old WKY, the
      relaxations to beraprost were maintained, but not those to prostacyclin. In SHR
      aorta, prostacyclin or beraprost produced no or minor relaxations, which, in
      younger SHR, were enhanced by Triplion. In both strains, the relaxations were
      inhibited by CAY-10441 (IP receptor antagonist). The relaxations to forskolin and
      isoproterenol were reduced with aging. When compared with those of WKY, the
      relaxations to isoproterenol were reduced in 3- but not in 6- or 15-mo-old SHR,
      whereas those to forskolin were consistently diminished at any given age.
      Whatever the age, prostacyclin and beraprost produced CAY-10441-sensitive
      inhibitions of ADP-induced platelet aggregation. Both agonists were more potent
      in SHR than in WKY. Therefore, in platelets from WKY and SHR, the IP receptor
      dependent antiaggregant response is functional and maintained during aging. In
      aorta from WKY those responses are reduced by aging and, in SHR, are already
      compromised at 3 mo. This dysfunction of the IP receptor is only partially
      explained by a general dysfunction of the adenylate cyclase pathway.

PMID- 18820029
TI  - Reverse changes in cardiac substrate oxidation in dogs recovering from heart
      failure.
AB  - When recovering from heart failure (HF), the myocardium displays a marked
      plasticity and can regain normal gene expression and function; however, recovery
      of substrate oxidation capacity has not been explored. We tested whether cardiac
      functional recovery is matched by normalization of energy substrate utilization
      during post-HF recovery. HF was induced in dogs by pacing the left ventricle (LV)
      at 210-240 beats/min for 4 wk. Tachycardia was discontinued, and the heart was
      allowed to recover. An additional group was studied in HF, and healthy dogs
      served as controls (n = 8/group). Cardiac free fatty acids (FFAs) and glucose
      oxidation were measured with [3H]oleate and [14C]glucose. At 10 days of recovery,
      hemodynamic parameters returned to control values; however, the contractile
      response to dobutamine remained depressed, LV end-diastolic volume was 28% higher
      than control, and the heart mass-to-body mass ratio was increased (9.8 +/- 0.4
      vs. 7.5 +/- 0.2 g/kg, P < 0.05). HF increased glucose oxidation (76.8 +/- 19.7
      nmol.min(-1).g(-1)) and decreased FFA oxidation (20.7 +/- 6.4 nmol.min(-1).g(
      1)), compared with normal dogs (24.5 +/- 6.3 and 51.7 +/- 9.6 nmol.min(-1).g(-1),
      respectively), and reversed to normal values at 10 days of recovery (25.4 +/- 6.0
      and 46.6 +/- 6.7 nmol.min(-1).g(-1), respectively). However, similar to HF, the
      recovered dogs failed to increase glucose and fatty acid uptake in response to
      pacing stress. The activity of myocardial citrate synthase and aconitase was
      significantly decreased during recovery compared with that in control dogs (58
      and 27% lower, respectively, P < 0.05), indicating a persistent reduction in
      mitochondrial oxidative capacity. In conclusion, cardiac energy substrate
      utilization is normalized in the early stage of post-HF recovery at baseline, but
      not under stress conditions.

PMID- 18820030
TI  - Phasic hemodynamics and reverse blood flows in the aortic isthmus and pulmonary
      arteries of preterm lambs with pulmonary vascular dysfunction.
AB  - Time-domain representations of the fetal aortopulmonary circulation were carried
      out in lamb fetuses to study hemodynamic consequences of congenital diaphragmatic
      hernia (CDH) and the effects of endothelin-receptor antagonist tezosentan (3
      mg/45 min). From the isthmic aortic and left pulmonary artery (PA) flows (Q) and
      isthmic aortic, PA, and left auricle pressures (P) on day 135 in 10 controls and
      7 CDH fetuses (28 ewes), discrete-triggered P and Q waveforms were modelized as
      Pt and Qt functions to obtain basic hemodynamic profiles, pulsatile waves [P, Q,
      and entry impedance (Ze)], and P and Q hysteresis loops. In the controls, blood
      propelling energy was accounted for by biventricular ejection flow waves (kinetic
      energy) with low Ze and by flow-driven pressure waves (potential energy) with low
      Ze. Weak fetal pulmonary perfusion was ensured by reflux (reverse flows) from PA
      branches to the ductus anteriosus and aortic isthmus as reverse flows. Endothelin
      receptor antagonist blockade using tezosentan slightly increased the forward flow
      but largely increased diastolic backward flow with a diminished left auricle pre-
      and postloading. In CHD fetuses, the static component overrode phasic flows that
      were detrimental to reverse flows and the direction of the diastolic isthmic flow
      changed to forward during the diastole period. Decreased cardiac output,
      flattened pressure waves, and increased forward Ze promoted backward flow to the
      detriment of forward flow (especially during diastole). Additionally, the
      intrapulmonary arteriovenous shunting was ineffective. The slowing of cardiac
      output, the dampening of energetic pressure waves and pulsatility, and the
      heightening of phasic impedances contributed to the lowering of aortopulmonary
      blood flows. We speculate that reverse pulmonary flow is a physiological
      requirement to protect the fetal pulmonary circulation from the prominent right
      ventricular stream and to enhance blood flow to the fetal heart and brain.

PMID- 18820031
TI  - Nitrite consumption in ischemic rat heart catalyzed by distinct blood-borne and
      tissue factors.
AB  - Nitric oxide (NO) may limit myocardial ischemia-reperfusion injury by slowing the
      mitochondrial metabolism. We examined whether rat heart contains catalysts
      potentially capable of reducing nitrite to NO during an episode of regional
      myocardial ischemia produced by temporary coronary artery occlusion. In intact
      Sprague-Dawley rats, a 15-min coronary occlusion lowered the nitrite
      concentration of the myocardial regions exhibiting ischemic glucose metabolism to
      approximately 50% that of nonischemic regions (185 +/- 223 vs. 420 +/- 203
      nmol/l). Nitrite was rapidly repleted during subsequent reperfusion. The heart
      tissue tested in vitro acquired a substantial ability to consume nitrite when
      made hypoxic at neutral pH, and this ability was slightly enhanced by
      simultaneously lowering the pH to 5.5. More than 70% of this activity could be
      abolished by flushing the coronary circulation with crystalloid to remove trapped
      erythrocytes. Correspondingly, erythrocytes demonstrated the ability to reduce
      exogenous nitrite to NO under hypoxic conditions in vitro. In erythrocyte-free
      heart tissue, the nitrite consumption increased fivefold when the pH was lowered
      to 5.5. Approximately 40% of this pH-sensitive increase in nitrite consumption
      could be blocked by the xanthine oxidoreductase inhibitor allopurinol, whereas
      lowering the Po(2) sufficiently to desaturate myoglobin accelerated it further.
      We conclude that rat heart contains several factors capable of catalyzing
      ischemic nitrite reduction; the most potent is contained within erythrocytes and
      activated by hypoxia, whereas the remainder includes xanthine oxidoreductase and
      other pH-sensitive factors endogenous to heart tissue, including deoxymyoglobin.

PMID- 18820032
TI  - Local BAFF gene silencing suppresses Th17-cell generation and ameliorates
      autoimmune arthritis.
AB  - Rheumatoid arthritis (RA) is a chronic disease characterized by synovial
      inflammation and joint damage. Although both T cells and B cells mediate the
      disease pathogenesis, proinflammatory cytokines are critically involved. The TNF
      superfamily member B cell-activating factor (BAFF) plays an important role in
      humoral immunity and in autoimmune diseases, including RA. Here, we show that
      intra-articular injection of lentivirus expressing shRNA for BAFF gene silencing
      provides long-term suppression of arthritic development in a collagen-induced
      arthritis model. Local BAFF gene targeting inhibited proinflammatory cytokine
      expression, suppressed generation of plasma cells and Th17 cells, and markedly
      ameliorated joint pathology. Lentivirus targets dendritic cells in the joint
      tissue and BAFF gene silencing inhibits dendritic cell maturation and their
      function in driving Th17-cell differentiation in vitro. Moreover, we revealed a
      previously unrecognized role for BAFF in promoting the expansion of Th17 cells
      and demonstrated IL-17 as a crucial effector cytokine for BAFF-mediated
      proinflammatory effects during collagen-induced arthritis development. Taken
      together, these findings identify BAFF as a valuable gene-silencing target
      potentially for the effective treatment of RA.

PMID- 18820033
TI  - The atypical Rac activator Dock180 (Dock1) regulates myoblast fusion in vivo.
AB  - Dock1 (also known as Dock180) is a prototypical member of a new family of
      atypical Rho GTPase activators. Genetic studies in Drosophila and Caenorhabditis
      elegans have demonstrated that Dock1 orthologues in these organisms have a
      crucial role in activating Rac GTPase signaling. We generated mutant alleles of
      the closely related Dock1 and Dock5 genes to study their function in mammals. We
      report that while Dock5 is dispensable for normal mouse embryogenesis, Dock1 has
      an essential role in embryonic development. A dramatic reduction of all skeletal
      muscle tissues is observed in Dock1-null embryos. Mechanistically, this embryonic
      defect is attributed to a strong deficiency in myoblast fusion, which is
      detectable both in vitro and in vivo. Furthermore, we have uncovered a
      contribution of Dock5 toward myofiber development. These studies identify Dock1
      and Dock5 as critical regulators of the fusion step during primary myogenesis in
      mammals and demonstrate that a specific component of the myoblast fusion
      machinery identified in Drosophila plays an evolutionarily conserved role in
      higher vertebrates.

PMID- 18820035
TI  - Role of tissue-type plasminogen activator in salicylic acid-induced sloughing of
      human corn tissue.
AB  - BACKGROUND: Plasminogen activators (PAs) and their regulatory counterparts, PA
      inhibitors (PAIs), play a role in normal differentiation processes and various
      pathophysiologic conditions of the epidermis. Normal desquamation of corneocytes
      from the skin3s surface may, in part, be regulated by the balanced activities of
      tissue-type PA (tPA) and PAI-2. Salicylic acid (SA) is commonly used to remove
      the hyperkeratotic tissue of corns, calluses, and verrucae, and it may disrupt
      intercellular adhesion structures; however, its exact mechanism of keratolytic
      action is poorly defined. We sought to determine the effects of SA by comparing
      the levels of PA and PAI messenger RNA (mRNA) in normal skin, untreated corns,
      and SA-treated corns. METHODS: Untreated and SA-treated human corn tissue samples
      were obtained from patients electing surgery to repair bony defects that underlay
      their lesions. Histopathologic examination of corns was performed by staining the
      tissue sections with hematoxylin and eosin and by light microscopy. Polymerase
      chain reaction was used to compare mRNA expression of PAs and PAIs in normal
      skin, untreated corns, and SA-treated corns. RESULTS: We demonstrated lower tPA
      and higher PAI-2 mRNA levels in corn tissue compared with normal skin. In corn
      tissue treated with SA, the expression of tPA mRNA increased and of PAI-2 mRNA
      decreased to the levels found in normal skin. CONCLUSION: An altered balance in
      tPA and PAI-2 levels contributes to the induction of hyperkeratotic corn tissue
      and suggests that the keratolytic action of SA is associated with its ability to
      stimulate proteinase-meditated desquamation processes.

PMID- 18820036
TI  - The incidence of tinea pedis in diabetic versus nondiabetic patients with
      interdigital macerations: a prospective study.
AB  - BACKGROUND: We sought to determine the incidence of tinea pedis in patients with
      otherwise asymptomatic pedal interdigital macerations. Both diabetic and
      nondiabetic populations were compared. Age and body mass index were also examined
      for their significance. METHODS: Fungal cultures of skin scrapings from 80
      patients (77 male and 3 female; mean age, 65 years) with interdigital macerations
      were performed; 40 patients had previously been diagnosed with type 2 diabetes
      and 40 did not have diabetes. RESULTS: Cultures revealed a 40% prevalence of
      tinea pedis in the total study population. The prevalence in the nondiabetic
      group was 37.5% and 42.5% for the diabetic group. This was not a statistically
      significant difference. Among patients with interdigital macerations that yielded
      positive fungal cultures, those in the nondiabetic group were 6.3 years older
      than those in the diabetic group. It was also observed that the nondiabetic
      patients with interdigital macerations yielding positive fungal cultures were 9.1
      years older than patients with negative fungal cultures in the nondiabetic group.
      CONCLUSION: The results of this study provide the practitioner with a guide for
      treating pedal interdigital macerations. Because the likelihood of a tinea pedis
      infection is 40%, it seems prudent to treat these macerations with an antifungal
      agent. In regard to age, the results suggest that as nondiabetic patients age,
      the likelihood of an otherwise asymptomatic interdigital maceration yielding a
      positive fungal culture increases, and that diabetic patients may be susceptible
      to interdigital fungal infections at a younger age than those without diabetes.

PMID- 18820034
TI  - Ceramide activates JNK to inhibit a cAMP-gated K+ conductance and Cl- secretion
      in intestinal epithelia.
AB  - Sphingomyelinases (SMases) hydrolyze membrane sphingomyelin to ceramide and are
      expressed by diverse host and microbial cell types populating mucosal surfaces.
      Exogenous bacterial SMase acts on the basolateral membrane of polarized human
      intestinal epithelial cells to repress the cAMP-induced Cl(-) secretory response,
      but how this occurs is unknown. We show here that SMase acts by down-regulating a
      cAMP-gated basolateral membrane K(+) conductance. Neither phosphocholine,
      ceramide-1-phosphate, nor sphingosine-1-phosphate recapitulates this effect,
      indicating that ceramide production is the decisive factor. Basolaterally applied
      SMase induced the phosphorylation of c-Jun NH(2)-terminal kinase (JNK), and
      inhibition of JNK rescued the effect of SMase on cAMP-dependant secretion. SMase
      secreted by normal human fibroblasts specifically recapitulated the effect on
      cAMP-induced Cl(-) secretion, indicating that cell types inhabiting the
      subepithelial space can provide such an activity to the basolateral membrane of
      intestinal enterocytes in trans. Thus, conversion of sphingomyelin to ceramide in
      basolateral membranes of intestinal cells rapidly activates JNK to inhibit a cAMP
      gated K(+) conductance and thereby attenuates Cl(-) secretion. These results
      define a novel lipid-mediated pathway for regulation of salt and water
      homeostasis at mucosal surfaces.

PMID- 18820037
TI  - The short-term effectiveness of full-contact custom-made foot orthoses and
      prefabricated shoe inserts on lower-extremity musculoskeletal pain: a randomized
      clinical trial.
AB  - BACKGROUND: Foot orthoses are commonly dispensed for musculoskeletal complaints
      of the foot and lower limb. Few randomized clinical trials evaluate the clinical
      effectiveness of foot orthoses. METHODS: In this randomized clinical trial with a
      crossover design, 42 participants wore custom orthoses and prefabricated inserts
      in their regular footwear for 4 weeks each, consecutively. Twenty-seven
      participants received prefabricated inserts first and 13 received custom orthoses
      first. A numeric pain rating scale (possible score, 0-10) was used to measure
      participant pain. RESULTS: Statistically and clinically important decreases in
      pain were reported after 3 weeks by participants wearing custom orthoses first (
      1.39 pain units, t(12) = 2.70, P = .02). Participants who wore prefabricated
      inserts first reported no statistically significant change in pain. When the
      alternative intervention was introduced, participants now wearing prefabricated
      inserts had greater pain after 1 and 2 weeks (1.1 pain units, t(12) = 3.09, P =
      .01 and 0.9 pain units, t(12) = 2.65, P = .02, respectively). Participants now
      wearing custom orthoses did not demonstrate significantly lower pain at any week
      compared with the second baseline but did have significantly lower pain scores
      compared with their initial baseline scores (-0.81 pain units, t(12) = 2.31, P =
      .03). CONCLUSION: Full-contact custom-made foot orthoses provide symptomatic
      relief after 3 weeks of use for patients with lower-extremity musculoskeletal
      pain if they are prescribed as the initial treatment.

PMID- 18820038
TI  - Metatarsus adductus angle in male and female feet: normal values with two
      measurement techniques.
AB  - BACKGROUND: The literature contains several techniques for calculating metatarsal
      adductus angle. Most common systems use the fourth metatarsal cuboid joint and
      the fifth metatarsal cuboid joint. Although both systems are quite different,
      normal values of metatarsus adductus angle have not been established with each
      system of measurement. METHODS: Two hundred six radiographic images of feet in
      dorsoplantar projection were used to measure the metatarsus adductus angle using
      two different reference points: the joint between the fourth metatarsal and the
      cuboid and the joint between the fifth metatarsal and the cuboid. RESULTS:
      Comparison of the results of the two measurement techniques showed significant
      differences (P < .05). The values of the metatarsus adductus angle also showed
      significant differences in men versus women (P < .05). The reliability of the
      measurements was checked by using an intra- and inter-evaluator test performed by
      two evaluators. CONCLUSION: Data showed the reliability of both systems of
      measurement, although significant differences in the metatarsal adductus angle
      mean value were found using these systems of measurement in the same foot. On the
      other hand, significant differences were found in mean values of metatarsus
      adductus angle between male and female feet.

PMID- 18820039
TI  - Surgical correlation of preoperative MRI findings of trauma to tendons and
      ligaments of the foot and ankle.
AB  - BACKGROUND: The purpose of this study was to determine whether magnetic resonance
      imaging findings are accurate and can be confirmed surgically. METHODS: Surgical
      correlation of preoperative magnetic resonance imaging findings of trauma to
      tendons and ligaments of the foot and ankle were retrospectively studied in 28
      patients who had undergone surgical repair for tears of the Achilles tendon,
      posterior tibial tendon, peroneal tendons, collateral ligaments, and other
      pathology. RESULTS: This study corroborates that magnetic resonance imaging
      findings are confirmed surgically 83% of the time for tears of tendons and
      ligaments of the foot and ankle. Larger tendons (Achilles, posterior tibial
      tendon) have a 94% sensitivity and 6% specificity, respectively. Collateral
      ligament and high ankle sprains have a 73% sensitivity. There is a lower
      sensitivity of 57% for peroneus brevis and longus ruptures. CONCLUSION: This
      study revealed that peroneal trauma can be an isolated event and in some cases
      can occur with other traumatic pathology such as collateral ligament tears.

PMID- 18820040
TI  - Computerized analysis of plantar pressure variation in flip-flops, athletic
      shoes, and bare feet.
AB  - BACKGROUND: High peak plantar pressures predispose to foot problems and may
      exacerbate existing conditions. For podiatric physicians to make educated
      recommendations to their patients, it is important and necessary to begin to look
      at different shoes and how they affect peak plantar pressure. METHODS: To
      determine how flip-flops change peak plantar pressure while walking, we compared
      peak plantar pressures in the same test subjects wearing flip-flops, wearing
      athletic shoes, and in bare feet. Ten women with size 7 feet and a body mass
      index less than 25 kg/m2 were tested with an in-shoe pressure-measurement system.
      These data were collected and analyzed by one-way analysis of variance and
      computer software. RESULTS: Statistically significant results were obtained for
      nine of the 18 comparisons. In each of these comparisons, flip-flops always
      demonstrated higher peak plantar pressures than athletic shoes but lower
      pressures than bare feet. CONCLUSION: Although these data demonstrate that flip
      flops have a minor protective role as a shock absorber during the gait cycle
      compared with pressures measured while barefoot, compared with athletic shoes,
      they increase peak plantar pressures, placing the foot at greater risk for
      pathologic abnormalities.

PMID- 18820041
TI  - Relationship of body mass index, ankle dorsiflexion, and foot pronation on
      plantar fascia thickness in healthy, asymptomatic subjects.
AB  - BACKGROUND: We sought to investigate the thickness of plantar fascia, measured by
      means of ultrasonographic evaluation in healthy, asymptomatic subjects, and its
      relationship to body mass index, ankle joint dorsiflexion range of motion, and
      foot pronation in static stance. METHODS: One hundred two feet of 51 healthy
      volunteers were examined. Sonographic evaluation with a 10-MHz linear array
      transducer was performed 1 and 2 cm distal to its insertion. Physical examination
      was also performed to assess body mass index, ankle joint dorsiflexion, and
      degree of foot pronation in static stance. Both examinations were performed in a
      blinded manner. RESULTS: Body mass index showed moderate correlation with plantar
      fascia thickness at the 1- and 2-cm locations. Ankle dorsiflexion range of motion
      showed no correlation at either location. Foot pronation showed an inverse
      correlation with plantar fascia thickness at the 2-cm location and no correlation
      at the 1-cm location. CONCLUSION: Body mass index and foot supination at the
      subtalar joint are related to increased thickness at the plantar fascia in
      healthy, asymptomatic subjects. Although the changes in thickness were small
      compared with those in patients with symptomatic plantar fasciitis, they could
      play a role in the mechanical properties of plantar fascia and in the development
      of plantar fasciitis.

PMID- 18820042
TI  - The flat-footed child -- to treat or not to treat: what is the clinician to do?
AB  - BACKGROUND: This article addresses the treatment of pediatric flatfoot with foot
      orthoses and explores the existing knowledge from an evidence-based perspective.
      METHODS: Studies investigating the use of foot orthoses for pediatric flatfoot
      were reviewed and ranked on the evidence hierarchy model according to research
      designs. Clinical guidelines and efficacy rating methods were also reviewed.
      RESULTS: Three randomized controlled trials exist, and a systematic review and
      possible meta-analysis of these studies is in progress. The results of these
      studies, although not definitive for the use of orthoses for pediatric flatfoot,
      provide useful direction. Clinical guidelines for the management of flatfoot are
      a useful supplement for clinical decision making and have been enhanced.
      CONCLUSION: This article presents a pragmatic and evidence-based clinical care
      pathway for clinicians to use for pediatric flatfoot. It uses a simple "traffic
      light" framework to identify three subtypes of pediatric flatfoot. The clinician
      is advised to 1) treat symptomatic pediatric flatfoot, 2) monitor (or with
      discretion simply treat) asymptomatic nondevelopmental pediatric flatfoot, and 3)
      identify and advise asymptomatic developmental pediatric flatfoot. (Children with
      juvenile arthritis should receive customized foot orthoses.) This approach will
      dispel much of the contention surrounding the use of foot orthoses in children.

PMID- 18820043
TI  - A comparison of rearfoot motion control and comfort between custom and semicustom
      foot orthotic devices.
AB  - BACKGROUND: Motion control and comfort are primary objectives in orthotic
      intervention. Semicustom orthotic devices have been presented as a more cost
      effective solution than custom orthotic devices. However, no studies have
      compared their function or comfort to that of custom orthotic devices. METHODS:
      Nineteen uninjured runners were fitted for custom and semicustom orthotic
      devices. Subjects underwent an instrumented gait analysis of running and walking
      in no-orthotic, custom orthotic, and semicustom orthotic conditions. Subjects
      completed visual analog scales for the custom and semicustom orthotic conditions.
      One-way repeated measures analyses of variance were performed on the rearfoot
      variables of peak eversion, eversion excursion, eversion duration, and eversion
      velocity. Two-tailed, dependent t tests were used to compare comfort. RESULTS:
      Eversion excursion showed significant differences between the conditions: during
      running, it was reduced in the custom orthotic as compared to the no-orthotic
      condition; during walking, it was reduced in the semicustom orthotic as compared
      to both the custom and no-orthotic conditions. The custom orthotic devices were
      significantly more comfortable (P < .05) than the semicustom devices in the area
      of the edges only. CONCLUSION: The results suggest that, in uninjured
      individuals, there are few differences in rearfoot motion control and comfort
      between the custom and semicustom orthotic devices used in this study.

PMID- 18820044
TI  - Ischemic contracture of deep posterior compartment of the leg following isolated
      ankle fracture.
AB  - Compartment syndromes and ischemic contractures after ankle fractures are
      exceedingly rare. We report a case in which a Weber type-C ankle fracture
      resulted in an unrecognized compartment syndrome and ischemic contracture of deep
      posterior compartment of the leg. Six weeks after injury, the patient had an
      obvious deformity and clawing of the toes. The deformities were corrected by
      lengthening the flexor hallucis longus and the flexor digitorum longus. Full
      correction of all clawed toes was evident. A deep posterior compartment syndrome
      may follow an ankle fracture and should be considered in any patient with
      unrelenting pain in the immediate postoperative period.

PMID- 18820045
TI  - Congenital clubfoot associated with an accessory soleus muscle.
AB  - A 16-month-old male with previously untreated bilateral clubfeet was admitted to
      S.B. Izmir Tepecik Education and Research Hospital, Izmir, Turkey. Both feet
      underwent surgical treatment. During surgery, an accessory soleus muscle was
      detected on the right side. The accessory soleus muscle had a distinct distal
      insertion at the superior anteromedial border of the calcaneus and also anterior
      and medial to the Achilles tendon. He was treated by bilateral complete subtalar
      release with Cincinnati incision, and the accessory soleus was also cut and the
      distal part resected. At the final follow-up visit, when the patient was 6 years
      and 9 months old, both feet had a normal appearance and appeared normal on
      radiograph and magnetic resonance imaging, with no presence of the accessory
      soleus muscle or its remnant. In our opinion, awareness of the association
      between an accessory soleus muscle and clubfoot, and sectioning of this muscle
      during surgery may improve surgical results.

PMID- 18820046
TI  - Mini-open technique for the achilles tenotomy in correction of idiopathic
      clubfoot: a report of 25 cases.
AB  - Achilles tenotomy is performed for the residual equinus deformity in the Ponseti
      method of clubfoot treatment. In the present article, we describe a mini-open
      Achilles tenotomy technique to prevent complications that could occur during
      tenotomy. This technique was performed on 15 patients (25 feet) during a 3-year
      period in our clinic on patients whose equinus deformities could not have been
      corrected by manipulations. Clear improvement (mean angle, 30 degrees ) was
      observed in equinus in our patients, and we have not seen any complication in
      this method. We conclude that direct visualizing of the tendon with mini-open
      incision may reduce the risk of neurovascular injury, especially for surgeons who
      are not experienced.

PMID- 18820047
TI  - Gauze application of phenol for matrixectomy.
AB  - Phenol matrixectomy is commonly used to treat onychocryptosis. The podiatric
      medical community has been progressively improving the technique of phenol
      application to avoid cases of burns. We describe a modification that uses gauze
      to provide a safe way for the phenol to be applied and prevents skin lesions due
      to phenol burns.

PMID- 18820048
TI  - Wound closure technique for lateral extensile approach to intra-articular
      calcaneal fractures.
AB  - Multiple wound closure techniques have been described for a lateral extensile
      calcaneal incision in the literature. In this article, a technique is presented
      that involves a subcutilar closure over a closed drain system, which has proven
      to be effective in minimizing sural nerve injury and wound dehiscence in open
      reduction internal fixation of 20 calcaneal fractures.

PMID- 18820050
TI  - Public health and podiatry.

PMID- 18820051
TI  - Biosynthesis of ubiquinone compounds with conjugated prenyl side chains.
AB  - Enzymatic steps from two different biosynthetic pathways were combined in
      Escherichia coli, directing the synthesis of a new class of biomolecules-
      ubiquinones with prenyl side chains containing conjugated double bonds. This was
      achieved by the activity of a C(30) carotenoid desaturase, CrtN, from
      Staphylococcus aureus, which exhibited an inherent flexibility in substrate
      recognition compared to other carotenoid desaturases. By utilizing the known
      plasticity of E. coli's native ubiquinone biosynthesis pathway and the unusual
      activity of CrtN, modified ubiquinone structures with prenyl side chains
      containing conjugated double bonds were generated. The side chains of the new
      structures were confirmed to have different degrees of desaturation by mass
      spectrometry and nuclear magnetic resonance analysis. In vivo (14)C labeling and
      in vitro activity studies showed that CrtN desaturates octaprenyl diphosphates
      but not the ubiquinone compounds directly. Antioxidant properties of conjugated
      side chain ubiquinones were analyzed in an in vitro beta-carotene-linoleate model
      system and were found to be higher than the corresponding unmodified ubiquinones.
      These results demonstrate that by combining pathway steps from different branches
      of biosynthetic networks, classes of compounds not observed in nature can be
      synthesized and structural motifs that are functionally important can be combined
      or enhanced.

PMID- 18820052
TI  - Immunofluorescence flow cytometry technique for enumeration of the brown-tide
      alga, Aureococcus anophagefferens.
AB  - A new immunologically based flow cytometry (IFCM) technique was developed to
      enumerate Aureococcus anophagefferens, a small pelagophyte alga that is the cause
      of "brown tides" in bays and estuaries of the mid-Atlantic states along the U.S.
      coast. The method utilizes a monoclonal antibody conjugated to fluorescein
      isothiocyanate (FITC-MAb) to label the surface of A. anophagefferens cells which
      are then detected and enumerated by using a flow cytometer. Optimal conditions
      for FITC-MAb staining, including solution composition, incubation times, and FITC
      MAb concentrations, were determined. The FITC-MAb method was tested for cross
      reactivity with nontarget, similarly sized, photoautotrophic protists, and the
      method was compared to an enzyme-linked immunosorbent assay (ELISA) using the
      same MAb. Comparisons of the IFCM technique to traditional microscopy enumeration
      of cultures and spiked environmental samples showed consistent agreement over
      several orders of magnitude (r(2) > 0.99). Comparisons of the IFCM and ELISA
      techniques for enumerating cells from a predation experiment showed a substantial
      overestimation (up to 10 times higher) of the ELISA in the presence of consumers
      of A. anophagefferens, presumably due to egested cell fragments that retained
      antigenicity, using the ELISA method, but were not characterized as whole algal
      cells by the IFCM method. Application of the IFCM method to environmental "brown
      tide" samples taken from the coastal bays of Maryland demonstrated its efficacy
      in resolving A. anophagefferens abundance levels throughout the course of a bloom
      and over a large range of abundance values. IFCM counts of the brown-tide alga
      from natural samples were consistently lower than those obtained using the ELISA
      method and were equivalent to those of the polyclonal immunofluorescence
      microscopy technique, since both methods discriminate intact cells. Overall, the
      IFCM approach was an accurate and relatively simple technique for the rapid
      enumeration of A. anophagefferens in natural samples over a wide range of
      abundance values (10(3) to 10(6) cells ml(-1)).

PMID- 18820053
TI  - Molecular microbial diversity survey of sponge reproductive stages and
      mechanistic insights into vertical transmission of microbial symbionts.
AB  - Many marine sponges, hereafter termed high-microbial-abundance (HMA) sponges,
      harbor large and complex microbial consortia, including bacteria and archaea,
      within their mesohyl matrices. To investigate vertical microbial transmission as
      a strategy to maintain these complex associations, an extensive phylogenetic
      analysis was carried out with the 16S rRNA gene sequences of reproductive (n =
      136) and adult (n = 88) material from five different Caribbean species, as well
      as all published 16S rRNA gene sequences from sponge offspring (n = 116). The
      overall microbial diversity, including members of at least 13 bacterial phyla and
      one archaeal phylum, in sponge reproductive stages is high. In total, 28 vertical
      transmission clusters, defined as clusters of phylotypes that are found both in
      adult sponges and their offspring, were identified. They are distributed among at
      least 10 bacterial phyla and one archaeal phylum, demonstrating that the complex
      adult microbial community is collectively transmitted through reproductive
      stages. Indications of host-species specificity and cospeciation were not
      observed. Mechanistic insights were provided using a combined electron microscopy
      and fluorescence in situ hybridization analysis, and an indirect mechanism of
      vertical transmission via nurse cells is proposed for the oviparous sponge
      Ectyoplasia ferox. Based on these phylogenetic and mechanistic results, we
      suggest the following symbiont transmission model: entire microbial consortia are
      vertically transmitted in sponges. While vertical transmission is clearly
      present, additional environmental transfer between adult individuals of the same
      and even different species might obscure possible signals of cospeciation. We
      propose that associations of HMA sponges with highly sponge-specific microbial
      communities are maintained by this combination of vertical and horizontal
      symbiont transmission.

PMID- 18820054
TI  - Quantitative rRNA-targeted solution-based hybridization assay using peptide
      nucleic acid molecular beacons.
AB  - The potential of a solution-based hybridization assay using peptide nucleic acid
      (PNA) molecular beacon (MB) probes to quantify 16S rRNA of specific populations
      in RNA extracts of environmental samples was evaluated by designing PNA MB probes
      for the genera Dechloromonas and Dechlorosoma. In a kinetic study with 16S rRNA
      from pure cultures, the hybridization of PNA MB to target 16S rRNA exhibited a
      higher final hybridization signal and a lower apparent rate constant than the
      hybridizations to nontarget 16S rRNAs. A concentration of 10 mM NaCl in the
      hybridization buffer was found to be optimal for maximizing the difference
      between final hybridization signals from target and nontarget 16S rRNAs.
      Hybridization temperatures and formamide concentrations in hybridization buffers
      were optimized to minimize signals from hybridizations of PNA MB to nontarget 16S
      rRNAs. The detection limit of the PNA MB hybridization assay was determined to be
      1.6 nM of 16S rRNA. To establish proof for the application of PNA MB
      hybridization assays in complex systems, target 16S rRNA from Dechlorosoma
      suillum was spiked at different levels to RNA isolated from an environmental
      (bioreactor) sample, and the PNA MB assay enabled effective quantification of the
      D. suillum RNA in this complex mixture. For another environmental sample, the
      quantitative results from the PNA MB hybridization assay were compared with those
      from clone libraries.

PMID- 18820055
TI  - Localization and expression of MreB in Vibrio parahaemolyticus under different
      stresses.
AB  - MreB, the homolog of eukaryotic actin, may play a vital role when prokaryotes
      cope with stress by altering their spatial organization, including their
      morphology, subcellular architecture, and localization of macromolecules. This
      study investigates the behavior of MreB in Vibrio parahaemolyticus under various
      stresses. The behavior of MreB was probed using a yellow fluorescent protein-MreB
      conjugate in merodiploid strain SC9. Under normal growth conditions, MreB formed
      helical filaments in exponential-phase cells. The shape of starved or stationary
      phase cells changed from rods to small spheroids. The cells differentiated into
      the viable but nonculturable (VBNC) state with small spherical cells via a
      "swelling-waning" process. In all cases, drastic remodeling of the MreB
      cytoskeleton was observed. MreB helices typically were loosened and fragmented
      into short filaments, arcs, and spots in bacteria under these stresses. The
      disintegrated MreB exhibited a strong tendency to attach to the cytoplasmic
      membrane. The expression of mreB generally declined in bacteria in the stationary
      phase and under starvation but was upregulated during the initial periods of cold
      shock and VBNC state differentiation and decreased afterwards. Our findings
      demonstrated the behavior of MreB in the morphological changes of V.
      parahaemolyticus under intrinsic or extrinsic stresses and may have important
      implications for studying the cellular stress response and aging.

PMID- 18820056
TI  - New strategy for isolating novel nematicidal crystal protein genes from Bacillus
      thuringiensis strain YBT-1518.
AB  - We have developed a strategy for isolating cry genes from Bacillus thuringiensis.
      The key steps are the construction of a DNA library in an acrystalliferous B.
      thuringiensis host strain and screening for the formation of crystal through
      optical microscopy observation and sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis (SDS-PAGE) analyses. By this method, three cry genes--cry55Aa1,
      cry6Aa2, and cry5Ba2--were cloned from rice-shaped crystals, producing B.
      thuringiensis YBT-1518, which consists of 54- and 45-kDa crystal proteins.
      cry55Aa1 encoded a 45-kDa protein, cry6Aa2 encoded a 54-kDa protein, and cry5Ba2
      remained cryptic in strain YBT-1518, as shown by SDS-PAGE or microscopic
      observation. Proteins encoded by these three genes are all toxic to the root knot
      nematode Meloidogyne hapla. The two genes cry55Aa1 and cry6Aa2 were found to be
      located on a plasmid with a rather small size of 17.7 kb, designated pBMB0228.

PMID- 18820057
TI  - Effects of therapeutic ceftiofur administration to dairy cattle on Escherichia
      coli dynamics in the intestinal tract.
AB  - The goal of this study was to follow ceftiofur-treated and untreated cattle in a
      normally functioning dairy to examine enteric Escherichia coli for changes in
      antibiotic resistance profiles and genetic diversity. Prior to treatment, all of
      the bacteria cultured from the cows were susceptible to ceftiofur. Ceftiofur
      resistant E. coli was only isolated from treated cows during and immediately
      following the cessation of treatment, and the 12 bla(CMY-2)-positive isolates
      clustered into two genetic groups. E. coli bacterial counts dropped significantly
      in the treated animals (P < 0.027), reflecting a disappearance of the antibiotic
      susceptible strains. The resistant bacterial population, however, did not
      increase in quantity within the treated cows; levels stayed low and were
      overtaken by a returning susceptible population. There was no difference in the
      genetic diversities of the E. coli between the treated and untreated cows prior
      to ceftiofur administration or after the susceptible population of E. coli
      returned in the treated cows. A cluster analysis of antibiotic susceptibility
      profiles resulted in six clusters, two of which were multidrug resistant and were
      comprised solely of isolates from the treated cows immediately following
      treatment. The antibiotic treatment provided a window to detect the presence of
      ceftiofur-resistant E. coli but did not appear to cause its emergence or result
      in its amplification. The finding of resistant isolates following antibiotic
      treatment is not sufficient to estimate the strength of selection pressure nor is
      it sufficient to demonstrate a causal link between antibiotic use and the
      emergence or amplification of resistance.

PMID- 18820058
TI  - Nitric oxide reductase gene expression and nitrous oxide production in nitrate
      grown Pseudomonas mandelii.
AB  - Pure cultures of Pseudomonas mandelii were incubated with or without nitrate,
      which acts as a substrate and an electron acceptor for denitrification. Nitric
      oxide reductase (cnorB) gene expression was measured using a quantitative reverse
      transcription-PCR, and nitrous oxide emissions were measured by gas
      chromatography. P. mandelii cells in either the presence or absence of nitrate
      demonstrated an increase in cnorB gene expression during the first 3 h of growth.
      The level of expression of cnorB in nitrate-amended cells remained high (average,
      2.06 x 10(8) transcripts/microg of RNA), while in untreated cells it decreased to
      an average of 3.63 x 10(6) transcripts/microg of RNA from 4 to 6 h. Nitrous oxide
      accumulation in the headspace was detected at 2 h, and cumulative emissions
      continued to increase over a 24-h period to 101 mumol in nitrate-amended cells.
      P. mandelii cnorB gene expression was not detected under aerobic conditions.
      These results demonstrate that P. mandelii cnorB gene expression was induced 203
      fold at 4 h when nitrate was present in the medium. Accumulations of N(2)O
      indicated that the cNorB enzyme was synthesized and active.

PMID- 18820059
TI  - Cloning and characterization of alpha-methylacyl coenzyme A racemase from
      Gordonia polyisoprenivorans VH2.
AB  - The mcr gene of Gordonia polyisoprenivorans VH2 is not clustered with genes
      required for rubber degradation. Its disruption by insertion of a kanamycin
      resistance cassette impaired growth on methyl-branched isoprenoids but not on
      linear hydrocarbons. Intact mcr from this bacterium or from Nocardia farcinica
      IFM 10152 complemented the mutant. Reverse transcription analysis showed similar
      mcr(VH2) expression results during cultivation with poly(cis-1,4-isoprene) and
      propionate. Additional genes coding for a putative cytochrome P450 monooxygenase
      and a short-chain dehydrogenase/reductase involved in beta-oxidation and poly(cis
      1,4-isoprene) degradation were also characterized.

PMID- 18820060
TI  - Microbiological analysis of food contact surfaces in child care centers.
AB  - A study of six child care centers was conducted to assess the microbiological
      quality of three food contact surfaces (one food serving surface and two food
      preparation surfaces) and one non-food contact surface (diaper changing surface)
      to determine the effectiveness of cleaning and sanitization procedures within the
      facilities. Aerobic plate counts (APCs) and Escherichia coli/coliform counts of
      50-cm(2) areas on all surfaces were determined using standard microbiological
      swabbing methods. Samples were taken three times a day (preopening, lunchtime,
      and following final cleanup) twice per month for 8 months in each child care
      center (n = 288 sampling times). Mean log APCs over the survey period were 1.32,
      1.71, 1.34, 1.96, 1.50, and 1.81 log CFU/50 cm(2) for the six centers. Mean log
      coliform counts were 0.15, 0.40, 0.33, 1.41, 0.28, and 1.12 CFU/50 cm(2) for the
      same centers. Coliforms were detected in 283 of 1,149 (24.7%) samples, with
      counts ranging from 1 to 2,000 CFU/50 cm(2), while E. coli was detected in 18 of
      1,149 (1.6%) samples, with counts ranging from 1 to 35 CFU/50 cm(2). The findings
      of this study demonstrated that the extent of bacterial contamination was
      dependent on the center, time of day, and the area sampled. While no direct
      correlation between contamination and illness can be made, given the high risk of
      food-borne illness associated with children, microbial contamination of food
      contact or non-food contact surfaces is an aspect of food safety that requires
      more attention. Emphasis on training and the development of modified standard
      sanitation operating procedures for child care centers are needed to reduce
      potential hazards.

PMID- 18820061
TI  - Modeling the variability of single-cell lag times for Listeria innocua
      populations after sublethal and lethal heat treatments.
AB  - Optical density measurements were used to estimate the effect of heat treatments
      on the single-cell lag times of Listeria innocua fitted to a shifted gamma
      distribution. The single-cell lag time was subdivided into repair time (the shift
      of the distribution assumed to be uniform for all cells) and adjustment time
      (varying randomly from cell to cell). After heat treatments in which all of the
      cells recovered (sublethal), the repair time and the mean and the variance of the
      single-cell adjustment time increased with the severity of the treatment. When
      the heat treatments resulted in a loss of viability (lethal), the repair time of
      the survivors increased with the decimal reduction of the cell numbers
      independently of the temperature, while the mean and variance of the single-cell
      adjustment times remained the same irrespective of the heat treatment. Based on
      these observations and modeling of the effect of time and temperature of the heat
      treatment, we propose that the severity of a heat treatment can be characterized
      by the repair time of the cells whether the heat treatment is lethal or not, an
      extension of the F value concept for sublethal heat treatments. In addition, the
      repair time could be interpreted as the extent or degree of injury with a
      multiple-hit lethality model. Another implication of these results is that the
      distribution of the time for cells to reach unacceptable numbers in food is not
      affected by the time-temperature combination resulting in a given decimal
      reduction.

PMID- 18820062
TI  - Mechanism of synergistic inhibition of Listeria monocytogenes growth by lactic
      acid, monolaurin, and nisin.
AB  - The combined lactic acid, monolaurin, and nisin effects on time-to-detection
      (optical density at 600 nm) extension were greater (P < 0.05) than any single or
      paired combination effect, which demonstrates a synergistic interaction among the
      antimicrobials. Monolaurin exposure caused C12:0 cell membrane incorporation.
      Lactic acid caused increased monolaurin C12:0 membrane incorporation, while nisin
      had no influence. We postulate that lactic acid-enhanced monolaurin C12:0
      incorporation into the cell membrane increased membrane fluidity resulting in
      increased nisin activity.

PMID- 18820063
TI  - Bioluminescent Aspergillus fumigatus, a new tool for drug efficiency testing and
      in vivo monitoring of invasive aspergillosis.
AB  - Aspergillus fumigatus is the main cause of invasive aspergillosis in
      immunocompromised patients, and only a limited number of drugs for treatment are
      available. A screening method for new antifungal compounds is urgently required,
      preferably an approach suitable for in vitro and in vivo studies. Bioluminescence
      imaging is a powerful tool to study the temporal and spatial resolutions of the
      infection and the effectiveness of antifungal drugs. Here, we describe the
      construction of a bioluminescent A. fumigatus strain by fusing the promoter of
      the glyceraldehyde-3-phosphate dehydrogenase gene from A. fumigatus with the
      luciferase gene from Photinus pyralis to control the expression of the
      bioluminescent reporter. A. fumigatus transformed with this construct revealed
      high bioluminescence under all tested growth conditions. Furthermore, light
      emission correlated with the number of conidia used for inoculation and with the
      biomass formed after different incubation times. The bioluminescent strains were
      suitable to study the effectiveness of antifungals in vitro by several
      independent methods, including the determination of light emission with a
      microplate reader and the direct visualization of light emission with an IVIS 100
      system. Moreover, when glucocorticoid-treated immunosuppressed mice were infected
      with a bioluminescent strain, light emission was detected from infected lungs,
      allowing the visualization of the progression of invasive aspergillosis.
      Therefore, this new bioluminescence tool is suitable to study the in vitro
      effectiveness of drugs and the disease development, localization, and burden of
      fungi within tissues and may also provide a powerful tool to study the
      effectiveness of antifungals in vivo.

PMID- 18820064
TI  - Inactivation of Mycobacterium avium complex by UV irradiation.
AB  - The effectiveness of two major UV technologies against a highly prevalent species
      of Mycobacterium avium complex was investigated. Our study indicates that M.
      avium is much more resistant to UV irradiation than most waterborne pathogens and
      that it is one of the rare microorganisms that are highly resistant to both
      chemical and UV disinfection in water.

PMID- 18820065
TI  - Effect of temperature on the cannibalistic behavior of Bacillus subtilis.
AB  - Bacillus subtilis resorts to cannibalism to delay sporulation under severe
      nutritional limitation. We report the effect of temperature on the dynamics of
      cannibalism demonstrated by B. subtilis. A model consisting of a delay
      differential equation may explain the effect of temperature on the dynamics of
      cannibalism.

PMID- 18820066
TI  - Comparison of extraintestinal pathogenic Escherichia coli strains from human and
      avian sources reveals a mixed subset representing potential zoonotic pathogens.
AB  - Since extraintestinal pathogenic Escherichia coli (ExPEC) strains from human and
      avian hosts encounter similar challenges in establishing infection in
      extraintestinal locations, they may share similar contents of virulence genes and
      capacities to cause disease. In the present study, 1,074 ExPEC isolates were
      classified by phylogenetic group and possession of 67 other traits, including
      virulence-associated genes and plasmid replicon types. These ExPEC isolates
      included 452 avian pathogenic E. coli strains from avian colibacillosis, 91
      neonatal meningitis E. coli (NMEC) strains causing human neonatal meningitis, and
      531 uropathogenic E. coli strains from human urinary tract infections. Cluster
      analysis of the data revealed that most members of each subpathotype represent a
      genetically distinct group and have distinguishing characteristics. However, a
      genotyping cluster containing 108 ExPEC isolates was identified, heavily mixed
      with regard to subpathotype, in which there was substantial trait overlap. Many
      of the isolates within this cluster belonged to the O1, O2, or O18 serogroup.
      Also, 58% belonged to the ST95 multilocus sequence typing group, and over 90% of
      them were assigned to the B2 phylogenetic group typical of human ExPEC strains.
      This cluster contained strains with a high number of both chromosome- and plasmid
      associated ExPEC genes. Further characterization of this ExPEC subset with
      zoonotic potential urges future studies exploring the potential for the
      transmission of certain ExPEC strains between humans and animals. Also, the
      widespread occurrence of plasmids among NMEC strains and members of the mixed
      cluster suggests that plasmid-mediated virulence in these pathotypes warrants
      further attention.

PMID- 18820067
TI  - Bioaccumulation, retention, and depuration of enteric viruses by Crassostrea
      virginica and Crassostrea ariakensis oysters.
AB  - Crassostrea ariakensis oysters are under review for introduction into the
      Chesapeake Bay. However, the human health implications of the introduction have
      not been fully addressed. This study evaluated rates of bioaccumulation,
      retention, and depuration of viruses by Crassostrea virginica and C. ariakensis
      when the two oyster species were maintained in separate tanks containing
      synthetic seawater of various salinities (8, 12, or 20 ppt). Oyster
      bioaccumulation tanks were seeded with 10(3) PFU/ml of hepatitis A virus (HAV),
      poliovirus, male-specific bacteriophage (MS2), and murine norovirus 1 (MNV-1) and
      10(3) PCR units/ml of human norovirus (NoV). After 24 h, depuration commenced as
      oysters (n = 255) were placed in pathogen-free seawater under continuous
      filtration. Oysters (n = 6) were sampled weekly for 1 month from each tank. Viral
      RNA was recovered using a modified proteinase K, guanidine, and glassmilk method
      and analyzed by quantitative reverse transcription-PCR. The odds of C. ariakensis
      oysters harboring NoV, MNV-1, or HAV were statistically greater than the odds of
      C. virginica oysters harboring the same viruses (MNV-1 odds ratio [OR], 4.5; P =
      0.01; NoV OR, 8.4; P < 0.001; HAV OR, 11.4; P < 0.001). Unlike C. virginica, C.
      ariakensis bioaccumulated and retained NoV, MNV-1, and HAV for 1 month at all
      salinities. Additionally, the odds of an oyster testing positive for NoV was 25.5
      times greater (P < 0.001) when the oyster also tested positive for MNV-1. This
      research helps assess the threat of C. ariakensis as a vehicle for viral
      pathogens due to the consumption of raw oysters and validates the role for MNV-1
      as a surrogate for NoV.

PMID- 18820068
TI  - Relative importance of Ixodes ricinus and Ixodes trianguliceps as vectors for
      Anaplasma phagocytophilum and Babesia microti in field vole (Microtus agrestis)
      populations.
AB  - The importance of Ixodes ricinus in the transmission of tick-borne pathogens is
      well recognized in the United Kingdom and across Europe. However, the role of
      coexisting Ixodes species, such as the widely distributed species Ixodes
      trianguliceps, as alternative vectors for these pathogens has received little
      attention. This study aimed to assess the relative importance of I. ricinus and
      I. trianguliceps in the transmission of Anaplasma phagocytophilum and Babesia
      microti among United Kingdom field voles (Microtus agrestis), which serve as
      reservoir hosts for both pathogens. While all instars of I. trianguliceps feed
      exclusively on small mammals, I. ricinus adults feed primarily on larger hosts
      such as deer. The abundance of both tick species and pathogen infection
      prevalence in field voles were monitored at sites surrounded with fencing that
      excluded deer and at sites where deer were free to roam. As expected, fencing
      significantly reduced the larval burden of I. ricinus on field voles and the
      abundance of questing nymphs, but the larval burden of I. trianguliceps was not
      significantly affected. The prevalence of A. phagocytophilum and B. microti
      infections was not significantly affected by the presence of fencing, suggesting
      that I. trianguliceps is their principal vector. The prevalence of nymphal and
      adult ticks on field voles was also unaffected, indicating that relatively few
      non-larval I. ricinus ticks feed upon field voles. This study provides compelling
      evidence for the importance of I. trianguliceps in maintaining these enzootic
      tick-borne infections, while highlighting the potential for such infections to
      escape into alternative hosts via I. ricinus.

PMID- 18820069
TI  - The Bacillus subtilis ydjL (bdhA) gene encodes acetoin reductase/2,3-butanediol
      dehydrogenase.
AB  - Bacillus subtilis is capable of producing 2,3-butanediol from acetoin by
      fermentation, but to date, the gene encoding the enzyme responsible, acetoin
      reductase/2,3-butanediol dehydrogenase (AR/BDH), has remained unknown. A search
      of the B. subtilis genome database with the amino acid sequences of functional
      AR/BDHs from Saccharomyces cerevisiae and Bacillus cereus resulted in the
      identification of a highly similar protein encoded by the B. subtilis ydjL gene.
      A knockout strain carrying a ydjL::cat insertion mutation was constructed, which
      (i) abolished 2,3-butanediol production in early stationary phase, (ii) produced
      no detectable AR or BDH activity in vitro, and (iii) accumulated the precursor
      acetoin in early stationary phase. The ydjL::cat mutation also affected the
      kinetics of lactate but not acetate production during stationary-phase
      cultivation with glucose under oxygen limitation. A very small amount of 2,3
      butanediol was detected in very-late-stationary-phase (96-hour) cultures of the
      ydjL::cat mutant, suggesting the existence of a second gene encoding a minor AR
      activity. From the data, it is proposed that the major AR/BDH-encoding gene ydjL
      be renamed bdhA.

PMID- 18820070
TI  - Cellulose degradation by micromonosporas recovered from freshwater lakes and
      classification of these actinomycetes by DNA gyrase B gene sequencing.
AB  - A number of Micromonospora strains isolated from the water column, sediment, and
      cellulose baits placed in freshwater lakes were shown to be able to degrade
      cellulose in lake water without any addition of nutrients. A selective isolation
      method was also developed to demonstrate that CFU arose from both spores and
      hyphae that inhabit the lake environment. Gyrase B gene sequencing performed on
      the isolates identified a number of new centers of variation within
      Micromonospora, but the most actively cellulolytic strains were recovered in a
      single cluster that equated with the type species of the genus, M. chalcea.

PMID- 18820071
TI  - csrA inhibits the formation of biofilms by Vibrio vulnificus.
AB  - PCR screening of the shellfish-borne pathogen Vibrio vulnificus revealed csrA
      negative strains, and these strains formed increased biofilm compared to csrA
      positive strains. Complementation in trans with csrA resulted in reduced biofilm
      formation, similar to that by csrA(+) strains. Our results provide evidence that
      csrA inhibits biofilm formation in V. vulnificus.

PMID- 18820073
TI  - Mechanisms of Cation Exchange by Pseudomonas aeruginosa PAO1 and PAO1 wbpL, a
      Strain with a Truncated Lipopolysaccharide.
AB  - The ability of bacterial cells to sequester cations is well recognized, despite
      the fact that the specific binding sites and mechanistic details of the process
      are not well understood. To address these questions, the cation-exchange behavior
      of Pseudomonas aeruginosa PAO1 cells with a truncated lipopolysaccharide (LPS)
      (PAO1 wbpL) and cells further modified by growth in a magnesium-deficient medium
      (PAO1 wbpL - Mg(2+)) were compared with that of wild-type P. aeruginosa PAO1
      cells. P. aeruginosa PAO1 cells had a negative surface charge (zeta potential)
      between pH 11 and 2.2, due to carboxylate groups present in the B-band LPS. The
      net charge on PAO1 wbpL cells was increasingly positive below pH 3.5, due to the
      influence of NH(3)(+) groups in the core LPS. The zeta potentials of these cells
      were also measured in Na(+), Ca(2+), and La(3+) electrolytes. Cells in the La(3+)
      electrolyte had a positive zeta potential at all pH values tested. Growing P.
      aeruginosa PAO1 wbpL in magnesium-deficient medium (PAO1 wbpL - Mg(2+)) resulted
      in an increase in its zeta potential in the pH range from 3.0 to 6.5. In cation
      exchange experiments carried out at neutral pH with either P. aeruginosa PAO1 or
      PAO1 wbpL, the concentration of bound Ca(2+) was found to decrease as the pH was
      reduced from 7.0 to 3.5. At pH 3.5, the bound Mg(2+) concentration decreased
      sharply, revealing the activity of surface sites for cation exchange and their pH
      dependence. Infrared spectroscopy of attached biofilms suggested that carboxylate
      and phosphomonoester functional groups within the core LPS are involved in cation
      exchange.

PMID- 18820072
TI  - Characterization of a T7-like lytic bacteriophage (phiSG-JL2) of Salmonella
      enterica serovar gallinarum biovar gallinarum.
AB  - PhiSG-JL2 is a newly discovered lytic bacteriophage infecting Salmonella enterica
      serovar Gallinarum biovar Gallinarum but is nonlytic to a rough vaccine strain of
      serovar Gallinarum biovar Gallinarum (SG-9R), S. enterica serovar Enteritidis, S.
      enterica serovar Typhimurium, and S. enterica serovar Gallinarum biovar Pullorum.
      The phiSG-JL2 genome is 38,815 bp in length (GC content, 50.9%; 230-bp-long
      direct terminal repeats), and 55 putative genes may be transcribed from the same
      strand. Functions were assigned to 30 genes based on high amino acid similarity
      to known proteins. Most of the expected proteins except tail fiber (31.9%) and
      the overall organization of the genomes were similar to those of yersiniophage
      phiYeO3-12. phiSG-JL2 could be classified as a new T7-like virus and represents
      the first serovar Gallinarum biovar Gallinarum phage genome to be sequenced. On
      the basis of intraspecific ratios of nonsynonymous to synonymous nucleotide
      changes (Pi[a]/Pi[s]), gene 2 encoding the host RNA polymerase inhibitor
      displayed Darwinian positive selection. Pretreatment of chickens with phiSG-JL2
      before intratracheal challenge with wild-type serovar Gallinarum biovar
      Gallinarum protected most birds from fowl typhoid. Therefore, phiSG-JL2 may be
      useful for the differentiation of serovar Gallinarum biovar Gallinarum from other
      Salmonella serotypes, prophylactic application in fowl typhoid control, and
      understanding of the vertical evolution of T7-like viruses.

PMID- 18820074
TI  - Accumulation of trans C18:1 fatty acids in the rumen after dietary algal
      supplementation is associated with changes in the Butyrivibrio community.
AB  - Optimization of the fatty acid composition of ruminant milk and meat is
      desirable. Dietary supplementation of algae was previously shown to inhibit rumen
      biohydrogenation, resulting in an altered milk fatty acid profile. Bacteria
      involved in biohydrogenation belong to the Butyrivibrio group. This study was
      aimed at relating accumulation of biohydrogenation intermediates with shifts in
      Butyrivibrio spp. in the rumen of dairy cows. Therefore, an experiment was
      performed with three rumen-fistulated dairy cows receiving a concentrate
      containing algae (9.35 g/kg total dry matter [DM] intake) for 20 days.
      Supplementation of the diet with algae inhibited biohydrogenation of C(18:2)
      omega 6 (n-6) and C(18:3) n-3, resulting in increased concentrations of
      biohydrogenation intermediates, whereas C(18:0) decreased. Addition of algae
      increased ruminal C(18:1) trans fatty acid concentrations, mainly due to 6- and
      20-fold increases in C(18:1) trans 11 (t11) and C(18:1) t10. The number of
      ciliates (5.37 log copies/g rumen digesta) and the composition of the ciliate
      community were unaffected by dietary algae. In contrast, supplementation of the
      diet with algae changed the composition of the bacterial community. Primers for
      the Butyrivibrio group, including the genera Butyrivibrio and Pseudobutyrivibrio,
      were specifically designed. Denaturing gradient gel electrophoresis showed
      community changes upon addition of algae without affecting the total amount of
      Butyrivibrio bacteria (7.06 log copies/g rumen DM). Clone libraries showed that
      algae affected noncultivated species, which cluster taxonomically between the
      genera Butyrivibrio and Pseudobutyrivibrio and might play a role in
      biohydrogenation. In addition, 20% of the clones from a randomly selected rumen
      sample were related to the C(18:0)-producing branch, although the associated
      C(18:0) concentration decreased through supplementation of the diet with algae.

PMID- 18820075
TI  - UGE1 and UGE2 regulate the UDP-glucose/UDP-galactose equilibrium in Cryptococcus
      neoformans.
AB  - The genome of the basidiomycete pathogenic yeast Cryptococcus neoformans carries
      two UDP-glucose epimerase genes (UGE1 and UGE2). UGE2 maps within a galactose
      cluster composed of a galactokinase homologue gene and a galactose-1-phosphate
      uridylyltransferase. This clustered organization of the GAL genes is similar to
      that in most of the hemiascomycete yeast genomes and in Schizosaccharomyces pombe
      but is otherwise not generally conserved in the fungal kingdom. UGE1 has been
      identified as necessary for galactoxylomannan biosynthesis and virulence. Here,
      we show that UGE2 is necessary for C. neoformans cells to utilize galactose as a
      carbon source at 30 degrees C but is not required for virulence. In contrast,
      deletion of UGE1 does not affect cell growth on galactose at this temperature. At
      37 degrees C, a uge2Delta mutant grows on galactose in a UGE1-dependent manner.
      This compensation by UGE1 of UGE2 mutation for growth on galactose at 37 degrees
      C was not associated with upregulation of UGE1 transcription or with an increase
      of the affinity of the enzyme for UDP-galactose at this temperature. We studied
      the subcellular localization of the two enzymes. Whereas at 30 degrees C, Uge1p
      is at least partially associated with intracellular vesicles and Uge2p is on the
      plasma membrane, in cells growing on galactose at 37 degrees C, Uge1p colocalizes
      with Uge2p to the plasma membrane, suggesting that its activity is regulated
      through subcellular localization.

PMID- 18820076
TI  - Deletion of the Plasmodium falciparum merozoite surface protein 7 gene impairs
      parasite invasion of erythrocytes.
AB  - Merozoite surface proteins have been implicated in the initial attachment to the
      host red blood cell membrane that begins the process of invasion, an important
      step in the life cycle of the malaria parasite. In Plasmodium falciparum,
      merozoite surface proteins include several glycosylphosphatidyl inositol-anchored
      proteins and peripheral proteins attached to the membrane through protein-protein
      interactions. The most abundant of these proteins is the merozoite surface
      protein 1 (MSP1) complex, encoded by at least three genes: msp1, msp6, and msp7.
      The msp7 gene is part of a six-member multigene family in Plasmodium falciparum.
      We have disrupted msp7 in the Plasmodium falciparum D10 parasite, as confirmed by
      Southern hybridization. Immunoblot and indirect immunofluorescence analyses
      confirmed the MSP7 null phenotype of D10DeltaMSP7 parasites. The synthesis,
      distribution, and processing of MSP1 were not affected in this parasite line. The
      level of expression and cellular distribution of the proteins MSP1, MSP3, MSP6,
      MSP9, and SERA5 remained comparable to those for the parental line. Furthermore,
      no significant change in the expression of MSP7-related proteins, except for that
      of MSRP5, was detected at the transcriptional level. The lack of MSP7 was not
      lethal at the asexual blood stage, but it did impair invasion of erythrocytes by
      merozoites to a significant degree. Despite this reduction in efficiency,
      D10DeltaMSP7 parasites did not show any obvious preference for alternate pathways
      of invasion.

PMID- 18820077
TI  - Changes in the N-glycome, glycoproteins with Asn-linked glycans, of Giardia
      lamblia with differentiation from trophozoites to cysts.
AB  - Giardia lamblia is present in the intestinal lumen as a binucleate, flagellated
      trophozoite or a quadranucleate, immotile cyst. Here we used the plant lectin
      wheat germ agglutinin (WGA), which binds to the disaccharide di-N-acetyl
      chitobiose (GlcNAc(2)), which is the truncated Asn-linked glycan (N-glycan) of
      Giardia, to affinity purify the N-glycomes (glycoproteins with N-glycans) of
      trophozoites and cysts. Fluorescent WGA bound to the perinuclear membranes,
      peripheral acidified vesicles, and plasma membranes of trophozoites. In contrast,
      WGA bound strongly to membranes adjacent to the wall of Giardia cysts and less
      strongly to the endoplasmic reticulum and acidified vesicles. WGA lectin-affinity
      chromatography dramatically enriched secreted and membrane proteins of Giardia,
      including proteases and acid phosphatases that retain their activities. With mass
      spectroscopy, we identified 91 glycopeptides with N-glycans and 194 trophozoite
      secreted and membrane proteins, including 42 unique proteins. The Giardia
      oligosaccharyltransferase, which contains a single catalytic subunit, preferred N
      glycosylation sites with Thr to those with Ser in vivo but had no preference for
      flanking amino acids. The most-abundant glycoproteins in the N-glycome of
      trophozoites were lysosomal enzymes, folding-associated proteins, and unique
      transmembrane proteins with Cys-, Leu-, or Gly-rich repeats. We identified 157
      secreted and membrane proteins in the Giardia cysts, including 20 unique
      proteins. Compared to trophozoites, cysts were enriched in Gly-rich repeat
      transmembrane proteins, cyst wall proteins, and unique membrane proteins but had
      relatively fewer Leu-rich repeat proteins, folding-associated proteins, and
      unique secreted proteins. In summary, there are major changes in the Giardia N
      glycome with the differentiation from trophozoites to cysts.

PMID- 18820078
TI  - Biofilm formation by Pneumocystis spp.
AB  - Pneumocystis spp. can cause a lethal pneumonia in hosts with debilitated immune
      systems. The manner in which these fungal infections spread throughout the lung,
      the life cycles of the organisms, and their strategies used for survival within
      the mammalian host are largely unknown, due in part to the lack of a continuous
      cultivation method. Biofilm formation is one strategy used by microbes for
      protection against environmental assaults, for communication and differentiation,
      and as foci for dissemination. We posited that the attachment and growth of
      Pneumocystis within the lung alveoli is akin to biofilm formation. An in vitro
      system comprised of insert wells suspended in multiwell plates containing
      supplemented RPMI 1640 medium supported biofilm formation by P. carinii (from
      rat) and P. murina (from mouse). Dramatic morphological changes accompanied the
      transition to a biofilm. Cyst and trophic forms became highly refractile and
      produced branching formations that anastomosed into large macroscopic clusters
      that spread across the insert. Confocal microscopy revealed stacking of viable
      organisms enmeshed in concanavalin A-staining extracellular matrix. Biofilms
      matured over a 3-week time period and could be passaged. These passaged organisms
      were able to cause infection in immunosuppressed rodents. Biofilm formation was
      inhibited by farnesol, a quorum-sensing molecule in Candida spp., suggesting that
      a similar communication system may be operational in the Pneumocystis biofilms.
      Intense staining with a monoclonal antibody to the major surface glycoproteins
      and an increase in (1,3)-beta-D-glucan content suggest that these components
      contributed to the refractile properties. Identification of this biofilm process
      provides a tractable in vitro system that should fundamentally advance the study
      of Pneumocystis.

PMID- 18820079
TI  - KMP-11, a basal body and flagellar protein, is required for cell division in
      Trypanosoma brucei.
AB  - Kinetoplastid membrane protein 11 (KMP-11) has been identified as a flagellar
      protein and is conserved among kinetoplastid parasites, but its potential
      function remains unknown. In a recent study, we identified KMP-11 as a
      microtubule-bound protein localizing to the flagellum as well as the basal body
      in both procyclic and bloodstream forms of Trypanosoma brucei (Z. Li, J. H. Lee,
      F. Chu, A. L. Burlingame, A. Gunzl, and C. C. Wang, PLoS One 3:e2354, 2008).
      Silencing of KMP-11 by RNA interference inhibited basal body segregation and
      cytokinesis in both forms and resulted in multiple nuclei of various sizes,
      indicating a continuous, albeit somewhat defective, nuclear division while cell
      division was blocked. KMP-11 knockdown in the procyclic form led to severely
      compromised formation of the new flagellum attachment zone (FAZ) and detachment
      of the newly synthesized flagellum. However, a similar phenotype was not observed
      in the bloodstream form depleted of KMP-11. Thus, KMP-11 is a flagellar protein
      playing critical roles in regulating cytokinesis in both forms of the
      trypanosomes. Its distinct roles in regulating FAZ formation in the two forms may
      provide a clue to the different mechanisms of cytokinetic initiation in procyclic
      and bloodstream trypanosomes.

PMID- 18820080
TI  - Genomics of Aspergillus oryzae: learning from the history of Koji mold and
      exploration of its future.
AB  - At a time when the notion of microorganisms did not exist, our ancestors
      empirically established methods for the production of various fermentation foods:
      miso (bean curd seasoning) and shoyu (soy sauce), both of which have been widely
      used and are essential for Japanese cooking, and sake, a magical alcoholic drink
      consumed at a variety of ritual occasions, are typical examples. A filamentous
      fungus, Aspergillus oryzae, is the key organism in the production of all these
      traditional foods, and its solid-state cultivation (SSC) has been confirmed to be
      the secret for the high productivity of secretory hydrolases vital for the
      fermentation process. Indeed, our genome comparison and transcriptome analysis
      uncovered mechanisms for effective degradation of raw materials in SSC: the
      extracellular hydrolase genes that have been found only in the A. oryzae genome
      but not in A. fumigatus are highly induced during SSC but not in liquid
      cultivation. Also, the temperature reduction process empirically adopted in the
      traditional soy-sauce fermentation processes has been found to be important to
      keep strong expression of the A. oryzae-specific extracellular hydrolases. One of
      the prominent potentials of A. oryzae is that it has been successfully applied to
      effective degradation of biodegradable plastic. Both cutinase, responsible for
      the degradation of plastic, and hydrophobin, which recruits cutinase on the
      hydrophobic surface to enhance degradation, have been discovered in A. oryzae.
      Genomic analysis in concert with traditional knowledge and technology will
      continue to be powerful tools in the future exploration of A. oryzae.

PMID- 18820081
TI  - Characterization of Arabidopsis lines deficient in GAPC-1, a cytosolic NAD
      dependent glyceraldehyde-3-phosphate dehydrogenase.
AB  - Phosphorylating glyceraldehyde-3-P dehydrogenase (GAPC-1) is a highly conserved
      cytosolic enzyme that catalyzes the conversion of glyceraldehyde-3-P to 1,3-bis
      phosphoglycerate; besides its participation in glycolysis, it is thought to be
      involved in additional cellular functions. To reach an integrative view on the
      many roles played by this enzyme, we characterized a homozygous gapc-1 null
      mutant and an as-GAPC1 line of Arabidopsis (Arabidopsis thaliana). Both mutant
      plant lines show a delay in growth, morphological alterations in siliques, and
      low seed number. Embryo development was altered, showing abortions and empty
      embryonic sacs in basal and apical siliques, respectively. The gapc-1 line shows
      a decrease in ATP levels and reduced respiratory rate. Furthermore, both lines
      exhibit a decrease in the expression and activity of aconitase and succinate
      dehydrogenase and reduced levels of pyruvate and several Krebs cycle
      intermediates, as well as increased reactive oxygen species levels. Transcriptome
      analysis of the gapc-1 mutants unveils a differential accumulation of transcripts
      encoding for enzymes involved in carbon partitioning. According to these studies,
      some enzymes involved in carbon flux decreased (phosphoenolpyruvate carboxylase,
      NAD-malic enzyme, glucose-6-P dehydrogenase) or increased (NAD-malate
      dehydrogenase) their activities compared to the wild-type line. Taken together,
      our data indicate that a deficiency in the cytosolic GAPC activity results in
      modifications of carbon flux and mitochondrial dysfunction, leading to an
      alteration of plant and embryo development with decreased number of seeds,
      indicating that GAPC-1 is essential for normal fertility in Arabidopsis plants.

PMID- 18820082
TI  - Root-secreted malic acid recruits beneficial soil bacteria.
AB  - Beneficial soil bacteria confer immunity against a wide range of foliar diseases
      by activating plant defenses, thereby reducing a plant's susceptibility to
      pathogen attack. Although bacterial signals have been identified that activate
      these plant defenses, plant metabolites that elicit rhizobacterial responses have
      not been demonstrated. Here, we provide biochemical evidence that the
      tricarboxylic acid cycle intermediate L-malic acid (MA) secreted from roots of
      Arabidopsis (Arabidopsis thaliana) selectively signals and recruits the
      beneficial rhizobacterium Bacillus subtilis FB17 in a dose-dependent manner. Root
      secretions of L-MA are induced by the foliar pathogen Pseudomonas syringae pv
      tomato (Pst DC3000) and elevated levels of L-MA promote binding and biofilm
      formation of FB17 on Arabidopsis roots. The demonstration that roots selectively
      secrete L-MA and effectively signal beneficial rhizobacteria establishes a
      regulatory role of root metabolites in recruitment of beneficial microbes, as
      well as underscores the breadth and sophistication of plant-microbial
      interactions.

PMID- 18820083
TI  - Unique and overlapping expression patterns among members of photosynthesis
      associated nuclear gene families in Arabidopsis.
AB  - Light provides crucial positional information in plant development, and the
      morphogenetic processes that are orchestrated by light signals are triggered by
      changes of gene expression in response to variations in light parameters. Control
      of expression of members of the RbcS and Lhc families of photosynthesis
      associated nuclear genes by light cues is a paradigm for light-regulated gene
      transcription, but high-resolution expression profiles for these gene families
      are lacking. In this study, we have investigated expression patterns of members
      of the RbcS and Lhc gene families in Arabidopsis (Arabidopsis thaliana) at the
      cellular level during undisturbed development and upon controlled interference of
      the light environment. Members of the RbcS and Lhc gene families are expressed in
      specialized territories, including root tip, leaf adaxial, abaxial, and epidermal
      domains, and with distinct chronologies, identifying successive stages of leaf
      mesophyll ontogeny. Defined spatial and temporal overlap of gene expression
      fields suggest that the light-harvesting and photosynthetic apparatus may have a
      different polypeptide composition in different cells and that such composition
      could change over time even within the same cell.

PMID- 18820086
TI  - School-based speech-language pathologists' perspectives on dysphagia management
      in the schools.
AB  - PURPOSE: Although provision of dysphagia services is within the scope of practice
      of speech-language pathologists (SLPs), little is known about the perspectives of
      school-based SLPs in relation to these services. The purpose of this study was to
      examine SLPs' perspectives related to school-based management of students with
      dysphagia. METHOD: Focus group interviews were conducted with 33 SLPs who were
      employed by a large school district in the Midwest before development of district
      supported policies and protocols related to dysphagia management. The interviews
      were analyzed using qualitative analysis methods. RESULTS: A variety of common
      perspectives emerged from the data, including a primary perceived difficulty in
      adapting practice in dysphagia from medical to educational service delivery
      models and settings. Additionally, 3 thematic categories of concerns emerged that
      were related to child characteristics, training, and support. IMPLICATIONS:
      Information gained in this investigation may be used to develop effective service
      delivery models, policies, and protocols, as well as to identify necessary
      supports related to the management of students with dysphagia in school settings.

PMID- 18820087
TI  - The effect of classroom amplification on the signal-to-noise ratio in classrooms
      while class is in session.
AB  - PURPOSE: The purpose of this study was to measure the signal-to-noise ratios in
      classrooms while class was in session and students were interacting with the
      teacher and each other. METHOD: Measurements of noise and reverberation were
      collected for 5 different classrooms in 3 different schools while class was in
      session. Activities taking place during the measurements were recorded to compare
      with sound level measures. The use of infrared classroom amplification was
      compared with no amplification. RESULTS/CONCLUSION: The results revealed that
      when classroom amplification was used, students heard the teacher's voice at a
      level that was an average of 13 dB above the noise floor as compared to an
      average of +2 dB above the noise floor without amplification.

PMID- 18820084
TI  - Physiological and transcriptomic evidence for a close coupling between
      chloroplast ontogeny and cell cycle progression in the pennate diatom Seminavis
      robusta.
AB  - Despite the growing interest in diatom genomics, detailed time series of gene
      expression in relation to key cellular processes are still lacking. Here, we
      investigated the relationships between the cell cycle and chloroplast development
      in the pennate diatom Seminavis robusta. This diatom possesses two chloroplasts
      with a well-orchestrated developmental cycle, common to many pennate diatoms. By
      assessing the effects of induced cell cycle arrest with microscopy and flow
      cytometry, we found that division and reorganization of the chloroplasts are
      initiated only after S-phase progression. Next, we quantified the expression of
      the S. robusta FtsZ homolog to address the division status of chloroplasts during
      synchronized growth and monitored microscopically their dynamics in relation to
      nuclear division and silicon deposition. We show that chloroplasts divide and
      relocate during the S/G2 phase, after which a girdle band is deposited to
      accommodate cell growth. Synchronized cultures of two genotypes were subsequently
      used for a cDNA-amplified fragment length polymorphism-based genome-wide
      transcript profiling, in which 917 reproducibly modulated transcripts were
      identified. We observed that genes involved in pigment biosynthesis and coding
      for light-harvesting proteins were up-regulated during G2/M phase and cell
      separation. Light and cell cycle progression were both found to affect
      fucoxanthin-chlorophyll a/c-binding protein expression and accumulation of
      fucoxanthin cell content. Because chloroplasts elongate at the stage of
      cytokinesis, cell cycle-modulated photosynthetic gene expression and synthesis of
      pigments in concert with cell division might balance chloroplast growth, which
      confirms that chloroplast biogenesis in S. robusta is tightly regulated.

PMID- 18820088
TI  - The use of conversational repairs by African American preschoolers.
AB  - PURPOSE: This study aimed to describe the types and frequency of conversational
      repairs used by African American (AA) children in relationship to their
      geographic locations and levels of performance on commonly used speech-language
      measures. METHOD: The strategies used to initiate repairs and respond to repair
      requests were identified in audiovisual records of spontaneous speech sampled
      from 120 Head Start students in Michigan (n = 69) and Louisiana (n = 51) at 3
      years of age. The 30-40-min samples were elicited with common stimuli and
      activities while the children interacted with an adult examiner. RESULTS: All
      participants initiated repairs and responded to examiner requests for
      conversational repairs. Some repair strategies were observed more often than
      others. The frequency, but not the types, of some of the strategies used varied
      significantly with participant location and level of speech-language performance.
      CONCLUSION: AA children used the same types of conversational repair strategies
      that have been observed among young speakers of Standard English varieties.
      CLINICAL IMPLICATION: Use of conversational repairs should be included among the
      pragmatic behaviors expected for 3-year-old AA children.

PMID- 18820089
TI  - Reading trajectories of children with language difficulties from preschool
      through fifth grade.
AB  - PURPOSE: The current work examined which theory of reading development, the
      cumulative reading trajectory or the compensatory trajectory of development, most
      accurately represents the reading trajectories of children with language
      difficulties (LD) relative to their peers with typical language (TL) skills.
      Specifically, initial levels of reading skills, overall rate of growth, and
      patterns of growth were examined. METHOD: Children were classified according to
      whether or not they exhibited LD at 54 months of age (LD n = 145; TL n = 653),
      using data from the National Institute of Child Health and Human Development's
      Early Child Care Research Network (see NICHD, 1993). A latent shape growth curve
      model was used to model reading skills at 4 time points from preschool through
      fifth grade. RESULTS: In comparison to children with TL, children with LD showed
      lower reading skills in preschool, but their overall reading growth was faster.
      All children developed the skills associated with reading more rapidly at earlier
      ages compared to later ages. Children with LD continued to exhibit reading skills
      that were substantially lower than those of children with TL during fifth grade.
      CONCLUSION: Results supported the compensatory trajectory of development. Speech
      language pathologists are encouraged to adopt evidence-based practices in order
      to boost reading outcomes for children with LD beginning in preschool.

PMID- 18820090
TI  - Developing treatment for adolescents who stutter: a phase I trial of the
      Camperdown Program.
AB  - PURPOSE: To investigate in detail how adolescents who stutter perform during
      treatment, with the aim of informing treatment development for this age group.
      METHOD: The Camperdown Program was conducted with 3 adolescents who stutter.
      Their performance during treatment was recorded in detail, and outcome measures
      were collected before treatment and on 5 occasions after treatment. RESULTS: One
      participant responded extremely well to treatment, with percentage of syllables
      stuttered (%SS) scores at 12 months follow-up around 1%. In addition, his speech
      naturalness was within normal limits. Another participant withdrew from treatment
      during maintenance, yet he still approximately halved his pretreatment %SS scores
      and was also sounding natural after treatment. This participant was satisfied
      with his treatment outcome. A third participant did not reach maintenance and did
      not benefit from the treatment. CONCLUSION: The adolescent who succeeded in
      treatment presented with a high level of self-confidence and maturity. When
      examining the factors that seemed to impact on treatment outcome, an underlying
      theme of decreased parent influence and increased peer influence and self
      direction was detected. These are fundamental during the journey through
      adolescence from childhood to adulthood. Future directions in developing
      treatments for adolescents are discussed.

PMID- 18820091
TI  - Verbal working memory and story retelling in school-age children with autism.
AB  - PURPOSE: This study examined verbal working memory and language ability in 15
      school-age children with autism using 3 verbal working memory tasks and 1 story
      recall task. METHOD: Three measures of verbal working memory--nonword repetition,
      memory for digits span, and sentence imitation--were given to children with
      autism and age-matched controls. Verbal working memory measures were chosen to
      reflect increasing levels of cognitive-linguistic complexity. Story retelling was
      measured using The Renfrew Bus Story (J. Cowley & C. Glasgow, 1994) and was
      scored for the percentage of propositions recalled and the average utterance
      length. RESULTS: A profile of verbal working memory deficits was seen in children
      with autism, with poorer performance on more complex verbal memory tasks.
      Performance on the 3 verbal memory tasks was independent of articulation ability.
      For the group with autism, receptive vocabulary was associated with sentence
      imitation and story recall but not with nonword repetition or digits span.
      Sentence imitation was related to story recall, but the relationship disappeared
      when the effect of vocabulary was removed. CONCLUSIONS: Vocabulary and language
      processing demands affect the performance of children with autism on tasks of
      verbal memory and story retelling. Results are viewed within a connectionist
      framework of verbal working memory.

PMID- 18820092
TI  - Phonemic awareness skill of speech-language pathologists and other educators.
AB  - PURPOSE: Educators rely on sufficient knowledge and skill to provide effective
      phonemic awareness instruction, an important component of early literacy
      instruction, particularly for children who experience difficulty learning to
      read. The purpose of this study was to evaluate and compare the phonemic
      awareness skill of several groups of educators, including speech-language
      pathologists (SLPs; n = 160), kindergarten teachers (n = 109), first-grade
      teachers (n = 112), reading teachers (n = 100), and special education teachers (n
      = 60). METHOD: Participants completed a paper-pencil measure of phonemic
      awareness skill that included 3 tasks. The measure was designed to assess
      sophisticated explicit phonemic awareness skill within a print context,
      representing an advanced skill level that has been deemed critical to teaching.
      RESULTS: SLPs demonstrated superior performance on the measure of phonemic
      awareness skill when compared to other educators (d = 1.54). The performance of
      reading and special education teachers was comparable to that of kindergarten and
      first-grade teachers. Orthographic knowledge had an adverse impact on the
      performance of all groups. However, SLPs were far more proficient than other
      educators at segmenting words that had a complex relationship between speech and
      print (e.g., box, use). CLINICAL IMPLICATIONS: SLPs have relative expertise in
      phonemic awareness, yet their performance may not be proficient. Three
      recommendations are discussed: (a) Increase the phonemic awareness skill of all
      educators, (b) revise instructional materials to enhance educators' efforts to
      provide accurate and effective phonemic awareness instruction, and (c) include
      SLPs as members of the team responsible for phonemic awareness instruction and
      intervention.

PMID- 18820093
TI  - Integrating American Indian/alaska Native culture into shared storybook
      intervention.
AB  - PURPOSE: The purpose of this clinical exchange is to provide information for
      speech-language pathologists (SLPs) so they will be able to provide culturally
      responsive intervention for young children of American Indian and Alaska Native
      heritage. The focus is on a particular strategy--the integration of culturally
      based stories into shared storybook intervention. METHOD: The use of culturally
      based stories is presented as it relates to sociocultural theory and the
      expressed priority of Native peoples to revitalize their cultural teaching and
      learning practices, inclusive of storytelling. Strategies are presented that SLPs
      can follow in preparing for the use of culturally based stories, as well as in
      ensuring that the stories that are selected for use are authentic and appropriate
      for the children involved. The strategies discussed represent the collaborative
      efforts of Native and non-Native professionals to link a review of pertinent
      scholarly literature with ancestral knowledge that is derived from tribal elders
      and tradition bearers of the Southern Puget Salish peoples. The article concludes
      by illustrating the application of these strategies to a program involving young
      children of culturally and linguistically diverse backgrounds. CONCLUSION: SLPs
      can integrate culturally based stories into their language and literacy
      intervention to encourage American Indian and Alaska Native children.

PMID- 18820094
TI  - Increased risk of falling in older community-dwelling women with mild cognitive
      impairment.
AB  - BACKGROUND: Falls are a major health care problem for older people and are
      associated with cognitive dysfunction. Mild cognitive impairment (MCI) is an
      increasingly recognized clinical problem. No study has comprehensively compared
      people with and without MCI for fall risk factors in both the physiological and
      cognitive domains. OBJECTIVE: The purpose of this cross-sectional study was to
      comprehensively compare fall risk factors in community-dwelling older women with
      and without MCI. DESIGN: A cross-sectional design was used in the study. METHODS:
      Community-dwelling women (N=158) with Folstein Mini Mental State Examination
      scores of >or=24 participated in the study. The Montreal Cognitive Assessment
      (MoCA) was used to categorize participants as either having or not having MCI.
      Each participant's fall risk profile was assessed with the Physiological Profile
      Assessment (PPA). Three central executive functions were assessed: (1) set
      shifting was assessed with the Trail Making Test (part B), (2) updating (ie,
      working memory) was assessed with the Verbal Digits Backward Test, and (3)
      response inhibition was assessed with the Stroop Colour-Word Test. RESULTS: Both
      the composite PPA score and its subcomponent, postural sway performance, were
      significantly different between the 2 groups; participants with MCI had higher
      composite PPA scores and greater postural sway compared with participants without
      MCI. Participants with MCI performed significantly worse on all 3 central
      executive function tests compared with participants without MCI. LIMITATIONS: A
      screening tool was used to categorize participants as having MCI, and fall risk
      factors were compared rather than the actual incidence of falls. CONCLUSIONS:
      Fall risk screening may be prudent in older adults with MCI.

PMID- 18820095
TI  - Continence and quality-of-life outcomes 6 months following an intensive pelvic
      floor muscle exercise program for female stress urinary incontinence: a
      randomized trial comparing low- and high-frequency maintenance exercise.
AB  - BACKGROUND AND OBJECTIVES: Few studies have examined the effectiveness of pelvic
      floor muscle (PFM) exercises to reduce female stress urinary incontinence (SUI)
      over the long term. This study: (1) evaluated continence and quality-of-life
      outcomes of women 6 months following formalized therapy and (2) determined
      whether low- and high-frequency maintenance exercise programs were equivalent in
      sustaining outcomes. SUBJECTS AND METHODS: Thirty-six women with SUI who
      completed an intensive PFM exercise intervention trial were randomly assigned to
      perform a maintenance exercise program either 1 or 4 times per week. Urine leaks
      per week, volume of urine loss, quality of life (Incontinence Impact
      Questionnaire [IIQ] score), PFM strength (Brink score), and prevalence of
      urodynamic stress incontinence (USI) were measured at a 6-month follow-up for
      comparison with postintervention status. Parametric and nonparametric statistics
      were used to determine differences in outcome status over time and between
      exercise frequency groups. RESULTS: Twenty-eight women provided follow-up data.
      Postintervention status was sustained at 6 months for all outcomes (mean [SD]
      urine leaks per week=1.2+/-2.1 versus 1.4+/-3.1; mean [SD] urine loss=0.2+/-0.5 g
      versus 0.2+/-0.8 g; mean [SD] IIQ score=17+/-20 versus 22+/-30; mean [SD] Brink
      score=11+/-1 versus 11+/-1; and prevalence of USI=48% versus 35%). Women assigned
      to perform exercises once or 4 times per week similarly sustained their
      postintervention status. DISCUSSION AND CONCLUSION: Benefits of an initial
      intensive intervention program for SUI were sustained over 6 months. However,
      only 15 of the 28 women provided documentation of their exercise adherence,
      limiting conclusions regarding the need for continued PFM exercise during follow
      up intervals of <or=6 months.

PMID- 18820096
TI  - Instability, laxity, and physical function in patients with medial knee
      osteoarthritis.
AB  - BACKGROUND AND PURPOSE: Studies have identified factors that contribute to
      functional limitations in people with knee osteoarthritis (OA), including
      quadriceps femoris muscle weakness, joint laxity, and reports of knee
      instability. However, little is known about the relationship among these factors
      or their relative influence on function. The purpose of this study was to
      investigate self-reported knee instability and its relationships with knee laxity
      and function in people with medial knee osteoarthritis (OA). PARTICIPANTS: Fifty
      two individuals with medial knee OA participated in the study. METHODS: Each
      participant was classified into 1 of 3 groups based on reports of knee
      instability. Limb alignment, knee laxity, and quadriceps femoris muscle strength
      (force-generating capacity) were assessed. Function was measured with the Knee
      Injury and Osteoarthritis Outcome Score (KOOS) and a stair-climbing test (SCT).
      Group differences were detected with one-way analyses of variance, and
      relationships among variables were assessed with the Eta(2) statistic and
      hierarchical regression analysis. RESULTS: There were no differences in
      alignment, laxity, or strength among the 3 groups. Self-reported knee instability
      did not correlate with medial laxity, limb alignment, or quadriceps femoris
      muscle strength. Individuals reporting worse knee instability scored worse on all
      subsets of the KOOS. Self-reported knee instability scores significantly
      contributed to the prediction of all measures of function above that explained by
      quadriceps femoris muscle force, knee laxity, and alignment. Neither laxity nor
      alignment contributed to any measure of function. DISCUSSION AND CONCLUSION: Self
      reported knee instability is a factor that is not directly associated with knee
      laxity and contributes to worse function. Further research is necessary to
      delineate the factors that contribute to self-reported knee instability and
      reduced function in this population.

PMID- 18820097
TI  - Hypophosphataemia at a large academic hospital in South Africa.
AB  - AIM: The aim of this study was to determine the most common causes of
      hypophosphataemia (<or=0.5 mmol/l) in a hospital population in order to identify
      patient groups at risk of developing the condition. METHODS: The study was
      conducted at Tygerberg Hospital, a tertiary care centre in the Western Cape,
      South Africa. All patients identified with a phosphate level <or=0.5 mmol/l
      during an 18-month period were included in the study. Medical records of these
      patients were reviewed. RESULTS: Of all the requests received for serum phosphate
      determination by the laboratory, 2% (861 out of 45 394 requests) were <or=0.5
      mmol/l. Thirty per cent (30%; n = 189) of the patients in the study population
      died during their hospital stay. Most (45%; n = 278) of the patients with low
      phosphate levels occurred in an intensive care setting, whereas 10% (n = 63) were
      most likely due to refeeding, and 6% (n = 35) had neoplastic disease. Sepsis was
      implicated as a contributing factor in 26% (n = 162). CONCLUSION: Severe
      hypophosphataemia is associated with a very high mortality (30%, n = 189).
      Patients with a high risk of developing hypophosphataemia include those in an
      intensive care unit (ICU), patients suffering from neoplastic diseases, possible
      refeeding syndrome and septic patients. Regular phosphate determination is
      recommended in these patients to facilitate early diagnosis of hypophosphataemia.

PMID- 18820098
TI  - Mesothelial reaction in longstanding Crohn's ileitis simulating papillary
      mesothelioma.
AB  - Intestinal and extraintestinal complications of Crohn's disease are well
      documented. Changes in the connective tissue within the intestinal wall and
      surrounding tissue including mesenteric fat are characteristically seen in
      resected and autopsy specimens. A rare and unusually florid mesothelial reaction
      in the surrounding small bowel serosa of a patient with a 2-year history of
      Crohn's ileitis is described. The peritoneal surface of the ileal resection
      specimen displayed exuberant tubulo-papillary formations of the mesothelium, with
      superficial invasion of the underlying stroma. The case demonstrates the well
      recognised difficult differential diagnosis between a benign mesothelial
      proliferation and malignant mesothelioma in a novel clinical setting, and the
      diversity of the extramural manifestations of Crohn's disease.

PMID- 18820099
TI  - NADH-cytochrome b5 reductase in a Turkish family with recessive congenital
      methaemoglobinaemia type I.
AB  - The development of cyanosis at birth, the so-called blue baby syndrome, alerts
      paediatricians to the presence of congenital heart disease. In rare cases where
      the arterial blood gas analysis is normal the cyanosis is a consequence of
      methaemoglobinaemia. There are three distinct origins of methaemoglobinaemia; the
      presence of a haemoglobin variant, environmental toxicity and deficiency of
      cytochrome b5 reductase (cb(5)r). Two children born to two sets of first-degree
      related parents were cyanotic from birth. Differential diagnosis eliminated
      cardiac and pulmonary abnormalities. Measurement of methaemoglobin levels
      confirmed recessive congenital methaemoglobinaemia (RCM) and treatment with
      ascorbic acid was commenced. In the absence of neurological defects, type I
      disease was diagnosed. Sequence analysis of CYB5R3 revealed two different
      missense mutations (one which is novel, Ile85Ser) in the two families. Neither of
      the mutations was located in the FAD or the NADH binding sites of cb(5)r, thus
      supporting a diagnosis of type I disease.

PMID- 18820100
TI  - Polymorphous low-grade adenocarcinoma of the nasopharynx: a case report and brief
      review.
AB  - Polymorphous low-grade adenocarcinoma (PLGA) is a rare tumour that mostly affects
      oral minor salivary glands. Our review of the literature found that there are
      only two reported cases of PLGA originating in the nasopharynx. Another
      nasopharyngeal PLGA in a 14-year-old boy is reported, focusing on the
      histopathological features and ultrastructural findings.

PMID- 18820101
TI  - Malignant perivascular epithelioid cell tumour of the fibula: a report and a
      short review of bone perivascular epithelioid cell tumour.
AB  - Perivascular epithelioid cell tumour (PEComa) is a term applied to a family of
      mesenchymal tumours composed of varying proportions of spindle and epithelioid
      cell components associated with HMB-45 expression. PEComa rarely arises in the
      soft tissue, visceral organs, skin and bone. This report details an instance when
      a purely epithelioid PEComa arose from the right fibula of a 52-year-old Chinese
      woman without features of tuberous sclerosis complex. The excision specimen
      disclosed an epithelioid tumour with a nested pattern associated with areas of
      nuclear pleomorphism, mitotic activity, necrosis and vascular invasion in
      addition to HMB-45 expression on immunohistochemistry. To the best of the
      authors' knowledge, this represents the first case of a histologically malignant
      PEComa of the bone. A short review of primary bone PEComas and potential problems
      in diagnosis is presented.

PMID- 18820102
TI  - Epithelioid perineurioma: an unusual variant.
AB  - An unusual epithelioid variant of perineurioma of the groin occurring in a 53
      year-old man is described. The lesion appeared to be associated with a femoral
      nerve branch. The tumour was characterised by the presence of a syncytial
      proliferation of epithelioid cells, mimicking a meningioma of syncytial type. In
      addition there was a minor component of a conventional perineurioma. The tumour
      cells were EMA+, claudin-1+ and collagen type IV+. Bcl 2 was focally expressed.
      This case highlights the possibility of a common histogenetic pathway for
      meningiomas and perineuriomas. Although ultrastructural evidence of possible
      meningiomatous differentiation within an otherwise histologically typical
      perineurioma has been described, this is the first reported case of an
      unconventional epithelioid variant of perineurioma, histologically resembling
      meningioma.

PMID- 18820103
TI  - Acute post-streptococcal glomerulonephritis associated with prolonged
      hypocomplementaemia.
AB  - The case of a 6-year-old boy who presented with acute post-streptococcal
      glomerulonephritis is reported. C3 levels and complement alternative pathway
      activity remained low for at least 10 months after presentation, before returning
      to normal. There was no evidence of other renal disease. This case highlights
      that hypocomplementaemia in acute post-streptococcal glomerulonephritis may
      persist for several months, and that prolonged hypocomplementaemia does not
      exclude this diagnosis.

PMID- 18820104
TI  - Plexiform angiomyxoid myofibroblastic tumour: differential diagnosis of
      gastrointestinal stromal tumour in the stomach.
AB  - Mesenchymal tumours other than gastrointestinal stromal tumours are rare in the
      stomach. Nevertheless it is important to incorporate them into the differential
      diagnosis. Plexiform angiomyxoid myofibroblastic tumour is a recently described
      new entity of a presumably benign mesenchymal gastric tumour. This report
      presents what is believed to be the third case of this tumour. The tumour is
      characterised by bland spindle cells in a plexiform pattern, a mucinous
      extracellular matrix and a network of thin blood vessels. These findings are
      completely in line with the two previous reported cases. There was a strong
      positivity for alpha-smooth muscle actin and a low proliferation index (<2%). The
      tumour had no C-KIT or CD34 expression and no mutation in the C-KIT and
      PDFGRalpha genes. Plexiform angiomyxoid myofibroblastic tumour may present a new
      mesenchymal tumour entity in the stomach.

PMID- 18820106
TI  - Recurrent pregnancy loss and inherited thrombophilia: who should be tested?

PMID- 18820107
TI  - Appendicectomy for obstructive appendicopathy.

PMID- 18820108
TI  - Comparison of examination of the entire cervix with routine cervical sampling in
      hysterectomy specimens from women with endometrial cancer: comment on a paper.

PMID- 18820109
TI  - Oestrogen receptor beta immunohistochemistry: time to get it right?

PMID- 18820111
TI  - Leukotriene receptor antagonist therapy and Churg-Strauss syndrome: culprit or
      innocent bystander?

PMID- 18820112
TI  - A breath of fresh air for acute oxygen treatment.

PMID- 18820113
TI  - Recent advances in exacerbations of COPD.

PMID- 18820114
TI  - Role of thrombolysis in haemodynamically stable patients with pulmonary embolism.

PMID- 18820116
TI  - A patient with bronchiectasis presented with progressive dyspnoea and an
      unresolved right lower lung infiltrate.

PMID- 18820120
TI  - Pulmonary veno-occlusive disease presenting with recurrent pulmonary oedema and
      the use of nitric oxide to predict response to sildenafil.
AB  - Pulmonary veno-occlusive disease (PVOD) is a disorder which causes progressive
      pulmonary hypertension, usually presenting with worsening dyspnoea and right
      heart failure. Pulmonary oedema induced by pulmonary vasodilator therapy to
      reduce pulmonary arterial pressure has been well described in PVOD, but here we
      describe a case of PVOD presenting with recurrent episodes of acute non
      cardiogenic pulmonary oedema, in the absence of significant pulmonary
      hypertension. Concern over the risk of precipitating pulmonary oedema led us to
      use inhaled nitric oxide to predict the safety and efficacy of sildenafil.

PMID- 18820121
TI  - Factors influencing delay in initiating antiretroviral therapy among HIV infected
      patients coinfected with tuberculosis.

PMID- 18820119
TI  - Obesity and the lung: 3. Obesity, respiration and intensive care.
AB  - Obesity is a major problem from a public health perspective and a difficult
      practical matter for intensivists. The obesity pandemic has required treating
      clinicians to develop an appreciation of the substantial pathophysiological
      effects of obesity on the various organ systems. The important physiological
      concepts are illustrated by focusing on obstructive sleep apnoea, obesity
      hypoventilation syndrome, abdominal compartment syndrome and ventilatory
      management of the obese patient with acute respiratory distress syndrome.

PMID- 18820122
TI  - Bronchial asthma on Mount Kilimanjaro is not a disadvantage.

PMID- 18820124
TI  - Renal impairment following aminoglycoside therapy in cystic fibrosis.

PMID- 18820125
TI  - Iatrogenic pulmonary artery pseudoaneurysm: images from different modalities.

PMID- 18820126
TI  - An intracellular loop 2 amino acid residue determines differential binding of
      arrestin to the dopamine D2 and D3 receptors.
AB  - Dopamine D(2) and D(3) receptors are similar subtypes with distinct interactions
      with arrestins; the D(3) receptor mediates less agonist-induced translocation of
      arrestins than the D(2) receptor. The goals of this study were to compare
      nonphosphorylated arrestin-binding determinants in the second intracellular
      domain (IC2) of the D(2) and D(3) receptors to identify residues that contribute
      to the differential binding of arrestin to the subtypes. Arrestin 3 bound to
      glutathione transferase (GST) fusion proteins of the D(2) receptor IC2 more
      avidly than to the D(3) receptor IC2. Mutagenesis of the fusion proteins
      identified a residue at the C terminus of IC2, Lys149, that was important for the
      preferential binding of arrestin 3 to D(2)-IC2; arrestin binding to D(2)-IC2
      K149C was greatly decreased compared with wild-type D(2)-IC2, whereas binding to
      the reciprocal mutant D(3)-IC2-C147K was enhanced compared with wild-type D(3)
      IC2. Mutating this lysine in the full-length D(2) receptor to cysteine decreased
      the ability of the D(2) receptor to mediate agonist-induced arrestin 3
      translocation to the membrane and decreased agonist-induced receptor
      internalization in human embryonic kidney 293 cells. The reciprocal mutation in
      the D(3) receptor increased receptor-mediated translocation of arrestin 3 without
      affecting agonist-induced receptor internalization. G protein-coupled receptor
      crystal structures suggest that Lys149, at the junction of IC2 and the fourth
      membrane-spanning helix, has intramolecular interactions that contribute to
      maintaining an inactive receptor state. It is suggested that the preferential
      agonist-induced binding of arrestin3 to the D(2) receptor over the D(3) receptor
      is due in part to Lys149, which could be exposed as a result of receptor
      activation.

PMID- 18820128
TI  - Endocrine-related resources from the National Institutes of Health.

PMID- 18820127
TI  - 90-kDa heat shock protein inhibition abrogates the topoisomerase I poison-induced
      G2/M checkpoint in p53-null tumor cells by depleting Chk1 and Wee1.
AB  - The G(2)/M cell cycle checkpoint is regulated by a multitude of signaling
      pathways after genotoxic stress. Herein, we report that treatment with the 90-kDa
      heat shock protein (Hsp90) molecular chaperone inhibitor 17-allylamino-17
      demethoxygeldanamycin (17AAG) selectively abrogates the G(2)/M checkpoint induced
      by 7-ethyl-10-hydroxycamptothecin (SN-38), an active metabolite of irinotecan, in
      p53-null compared with p53-intact HCT116 colon cancer cells. The basis for this
      selectivity can be explained in part by the lack of p21 induction in p53-null
      cells. In accord with published results, we could show that treatment with 17AAG
      resulted in depletion of Chk1, a known Hsp90 client protein. In addition, we
      observed a time- and dose-dependent decrease in Wee1 kinase level, a negative
      regulator of mitosis, after 17AAG treatment in gastrointestinal cancer cells.
      Depletion of Wee1 protein preceded mitotic entry induced by 17AAG, and this
      decrease could be partially rescued by cotreatment with a proteasome inhibitor.
      Coimmunoprecipitation experiments showed that Hsp90 and Wee1 interacted in whole
      cells, and 17AAG treatment decreased the degradative half-life of Wee1,
      indicating that Wee1 is another Hsp90 client in mammalian cells. Knockdown of
      Chk1 and Wee1 by short interfering RNA each resulted in abrogation of the G(2)/M
      checkpoint induced by SN-38. The combination of SN-38 and 17AAG was shown to be
      synergistic in p53-null but not in parental HCT116 cells by median
      effect/combination index analysis. Taken together, 17AAG specifically inhibits
      the G(2)/M checkpoint in p53-defective cells by down-regulation of two critical
      checkpoint kinases, Chk1 and Wee1.

PMID- 18820129
TI  - How we treat a hemophilia A patient with a factor VIII inhibitor.
AB  - The most significant complication of treatment in patients with hemophilia A is
      the development of alloantibodies that inhibit factor VIII activity. In the
      presence of inhibitory antibodies, replacement of the missing clotting factor by
      infusion of factor VIII becomes less effective. Once replacement therapy is
      ineffective, acute management of bleeding requires agents that bypass factor VIII
      activity. Long-term management consists of eradicating the inhibitor through
      immune tolerance. Despite success in the treatment of acute bleeding and
      inhibitor eradication, there remains an inability to predict or prevent inhibitor
      formation. Ideally, prediction and ultimately prevention will come with an
      improved understanding of how patient-specific and treatment-related factors work
      together to influence anti-factor VIII antibody production.

PMID- 18820130
TI  - Aurora-A kinase: a novel target of cellular immunotherapy for leukemia.
AB  - Aurora-A kinase (Aur-A) is a member of the serine/threonine kinase family that
      regulates the cell division process, and has recently been implicated in
      tumorigenesis. In this study, we identified an antigenic 9-amino-acid epitope
      (Aur-A(207-215): YLILEYAPL) derived from Aur-A capable of generating leukemia
      reactive cytotoxic T lymphocytes (CTLs) in the context of HLA-A*0201. The
      synthetic peptide of this epitope appeared to be capable of binding to HLA-A*2402
      as well as HLA-A*0201 molecules. Leukemia cell lines and freshly isolated
      leukemia cells, particularly chronic myelogenous leukemia (CML) cells, appeared
      to express Aur-A abundantly. Aur-A-specific CTLs were able to lyse human leukemia
      cell lines and freshly isolated leukemia cells, but not normal cells, in an HLA
      A*0201-restricted manner. Importantly, Aur-A-specific CTLs were able to lyse
      CD34+ CML progenitor cells but did not show any cytotoxicity against normal CD34+
      hematopoietic stem cells. The tetramer assay revealed that the Aur-A(207-215)
      epitope-specific CTL precursors are present in peripheral blood of HLA-A*0201
      positive and HLA-A*2402-positive patients with leukemia, but not in healthy
      individuals. Our results indicate that cellular immunotherapy targeting Aur-A is
      a promising strategy for treatment of leukemia.

PMID- 18820131
TI  - Antileukemic effects of the novel, mutant FLT3 inhibitor NVP-AST487: effects on
      PKC412-sensitive and -resistant FLT3-expressing cells.
AB  - An attractive target for therapeutic intervention is constitutively activated,
      mutant FLT3, which is expressed in a subpopulation of patients with acute
      myelocyic leukemia (AML) and is generally a poor prognostic indicator in patients
      under the age of 65 years. PKC412 is one of several mutant FLT3 inhibitors that
      is undergoing clinical testing, and which is currently in late-stage clinical
      trials. However, the discovery of drug-resistant leukemic blast cells in PKC412
      treated patients with AML has prompted the search for novel, structurally diverse
      FLT3 inhibitors that could be alternatively used to override drug resistance.
      Here, we report the potent and selective antiproliferative effects of the novel
      mutant FLT3 inhibitor NVP-AST487 on primary patient cells and cell lines
      expressing FLT3-ITD or FLT3 kinase domain point mutants. NVP-AST487, which
      selectively targets mutant FLT3 protein kinase activity, is also shown to
      override PKC412 resistance in vitro, and has significant antileukemic activity in
      an in vivo model of FLT3-ITD(+) leukemia. Finally, the combination of NVP-AST487
      with standard chemotherapeutic agents leads to enhanced inhibition of
      proliferation of mutant FLT3-expressing cells. Thus, we present a novel class of
      FLT3 inhibitors that displays high selectivity and potency toward FLT3 as a
      molecular target, and which could potentially be used to override drug resistance
      in AML.

PMID- 18820132
TI  - FOXP3 expression accurately defines the population of intratumoral regulatory T
      cells that selectively accumulate in metastatic melanoma lesions.
AB  - Regulatory T (T(reg)) cells are often found in human tumors; however, their
      functional characteristics have been difficult to evaluate due to low cell
      numbers and the inability to adequately distinguish between activated and T(reg)
      cell populations. Using a novel approach, we examined the intracellular cytokine
      production capacity of tumor-infiltrating T cells in the single-cell suspensions
      of enzymatically digested tumors to differentiate T(reg) cells from effector T
      cells. Similar to T(reg) cells in the peripheral blood of healthy individuals,
      tumor-infiltrating FOXP3(+)CD4 T cells, unlike FOXP3(-) T cells, were unable to
      produce IL-2 and IFN-gamma upon ex vivo stimulation, indicating that FOXP3
      expression is a valid biological marker for human T(reg) cells even in the tumor
      microenvironment. Accordingly, we enumerated FOXP3(+)CD4 T(reg) cells in
      intratumoral and peritumoral sections of metastatic melanoma tumors and found a
      significant increase in proportion of FOXP3(+)CD4 T(reg) cells in the
      intratumoral compared with peritumoral areas. Moreover, their frequencies were 3-
      to 5-fold higher in tumors than in peripheral blood from the same patients or
      healthy donors, respectively. These findings demonstrate that the tumor
      infiltrating CD4 T(reg) cell population is accurately depicted by FOXP3
      expression, they selectively accumulate in tumors, and their frequency in
      peripheral blood does not properly reflect tumor microenvironment.

PMID- 18820133
TI  - Intestinal double-positive CD4+CD8+ T cells of neonatal rhesus macaques are
      proliferating, activated memory cells and primary targets for SIVMAC251
      infection.
AB  - Peripheral blood and thymic double-positive (DP) CD4(+)CD8(+) T cells from
      neonates have been described earlier, but the function and immunophenotypic
      characteristics of other tissue-derived DP T cells are not clearly understood.
      Here, we demonstrate the functional and immunophenotypic characteristics of DP
      cells in 6 different tissues, including thymus from normal neonatal rhesus
      macaques (Macaca mulatta) between 0 and 21 days of age. In general, intestinal DP
      T cells of neonates have higher percentages of memory markers
      (CD28(+)CD95(+)CD45RA(low)CD62L(low)) and proliferation compared with single
      positive (SP) CD4(+) and CD8(+) T cells. In addition, percentages of DP T cells
      increase and CD62L expression decreases as animals mature, suggesting that DP
      cells mature and proliferate with maturity and/or antigen exposure. Consistent
      with this, intestinal DP T cells in neonates express higher levels of CCR5 and
      are the primary targets in simian immunodeficiency virus (SIV) infection.
      Finally, DP T cells produce higher levels of cytokine in response to mitogen
      stimulation compared with SP CD4(+) or CD8(+) T cells. Collectively, these
      findings demonstrate that intestinal DP T cells of neonates are proliferating,
      activated memory cells and are likely involved in regulating immune responses, in
      contrast to immature DP T cells in the thymus.

PMID- 18820135
TI  - A positive modulator of K Ca 2 and K Ca 3 channels, 4,5-dichloro-1,3-diethyl-1,3
      dihydro-benzoimidazol-2-one (NS4591), inhibits bladder afferent firing in vitro
      and bladder overactivity in vivo.
AB  - Calcium-activated potassium channels are attractive targets for the development
      of therapeutics for overactive bladder. In the current study, we addressed the
      role of calcium-activated potassium channels of small (SK; K(Ca)2) and
      intermediate (IK; K(Ca)3) conductance in bladder function pharmacologically. We
      identified and characterized a novel positive modulator of SK/IK channels, 4,5
      dichloro-1,3-diethyl-1,3-dihydro-benzoimidazol-2-one (NS4591). In whole-cell
      patch-clamp experiments, NS4591 doubled IK-mediated currents at a concentration
      of 45 +/- 6 nM(n = 16), whereas 530 +/- 100 nM (n = 7) was required for doubling
      of SK3-mediated currents. In acutely dissociated bladder primary afferent
      neurons, the presence of SK channels was verified using apamin and 1-ethyl-2
      benzimidazolinone. In these neurons, NS4591 (10 microM) inhibited the number of
      action potentials generated by suprathreshold depolarizing pulses. NS4591 also
      reduced carbachol-induced twitches in rat bladder detrusor rings in an apamin
      sensitive manner. In vivo, NS4591 (30 mg/kg) inhibited bladder overactivity in
      rats and cats induced by capsaicin and acetic acid, respectively. In conclusion,
      the present study supports the involvement of calcium-activated potassium
      channels in bladder function and identifies NS4591 as a potent modulator of IK
      and SK channels that is effective in animal models of bladder overactivity.

PMID- 18820134
TI  - Tumor necrosis factor alpha is a proximal mediator of synergistic hepatotoxicity
      from trovafloxacin/lipopolysaccharide coexposure.
AB  - The use of trovafloxacin (TVX), a fluoroquinolone antibiotic, was severely
      restricted because of an association of TVX therapy with idiosyncratic
      hepatotoxicity in patients. The mechanisms underlying idiosyncratic toxicity are
      unknown; however, one hypothesis is that an inflammatory stress can render an
      individual sensitive to the drug. Previously, we reported that treatment of mice
      with TVX and lipopolysaccharide (LPS) induced tumor necrosis factor (TNF) alpha
      dependent liver injury, whereas TVX or LPS treatment alone was nontoxic. The goal
      of this study was to elucidate the role of TNFalpha in TVX/LPS-induced liver
      injury. TNF receptor (TNFR) 1 p55(-/-) and TNFR2 (p75(-/-)) mice were protected
      from hepatotoxicity caused by TVX/LPS coexposure, suggesting that TVX/LPS-induced
      liver injury requires both TNF receptors. TNFalpha inhibition using etanercept
      significantly reduced the TVX/LPS-induced increases in the plasma concentrations
      of several cytokines around the time of onset of liver injury. However, despite
      the reduction in chemokines, etanercept treatment did not affect the TVX/LPS
      induced hepatic accumulation of neutrophils. In addition, etanercept treatment
      attenuated TVX/LPS induction of plasminogen activator inhibitor-1, and this was
      associated with a reduction in hepatic fibrin deposition. Mice treated with TVX
      and a nontoxic dose of TNFalpha also developed liver injury. In summary, TNFalpha
      acts through p55 and p75 receptors to precipitate an innocuous inflammatory
      cascade. TVX enhances this cascade, converting it into one that results in
      hepatocellular injury.

PMID- 18820136
TI  - Catecholamines relax detrusor through beta 2-adrenoceptors in mouse and beta 3
      adrenoceptors in man.
AB  - (-)-Isoproterenol [4-[1-hydroxy-2-[(1-methylethyl)amino]ethyl]-1,2-benzene diol
      hydrochloride] relaxes murine detrusor through beta-adrenoceptors (ARs); however,
      the beta-AR subtypes involved are unknown. beta(2)-ARs have been associated with
      caveolae, plasma-lemmal scaffolding domains that are absent in caveolin-1 (cav-1)
      knockout (KO) mice. Here, we studied detrusor responses in the absence and
      presence of beta-AR subtype-selective antagonists in wild-type (WT) and cav-1 KO
      mice. To inquire whether the murine detrusor model is relevant to man, beta-AR
      subtypes that mediate (-)-isoproterenol-evoked human detrusor relaxation were
      investigated. In WT mice, (-)-isoproterenol concentration-dependently relaxed the
      KCl (40 mM)-precontracted detrusor (-logEC(50)M = 8.04, E(max) = 62%). The
      effects of (-)-isoproterenol were surmountably antagonized by the beta(2)-AR
      selective antagonist ICI 118,551 [(+/-)-1-[2,3-(dihydro-7-methyl-1H-inden-4
      yl)oxy]-3-[(1-methylethyl)amino]-2-butanol] (pK(B) = 9.28) but not affected by
      the beta(1)-AR-selective antagonist CGP 20712 [1-[2-((3-carbamoyl-4
      hydroxy)phenoxy)ethylamino]-3-[4-(1-methyl-4-trifluoromethyl-2
      imidazolyl)phenoxy]-2-propanol] and beta(3)-AR-selective L-748,337 [(S)-M-[4-[2
      [3-[3-[acetamidomethyl)phenoxy)-2-hydroxypropyl]-amino]-ethyl]
      phenylbenzsulfonamide)], suggesting involvement of beta(2)-AR only. The cav-1 KO
      detrusor displayed significant contractile dysfunction. (-)-Isoproterenol was
      less potent and efficient in relaxing detrusor from cav-1 KO (-logEC(50)M, 7.76;
      E(max) = 44%), but ICI 118,551 caused similar antagonism (pK(B) = 9.15),
      suggesting that beta(2)-AR function persisted in cav-1 KO. The beta(3)-AR
      selective antagonist L-748,337 in the presence of ICI 118,551 and CGP 20712
      caused additional blockade of (-)-isoproterenol effects in cav-1 KO, consistent
      with a beta(3)-AR involvement during relaxation and suppression of this effect in
      WT. (-)-Isoproterenol relaxed human detrusor muscle precontracted with carbachol
      (-logEC(50)M = 6.39, E(max) = 52%). However, the effects of (-)-isoproterenol in
      human detrusor were not blocked by CGP 20712 or ICI 118,551 but antagonized by L
      748,337 (pK(B) = 7.65). We conclude that murine detrusor relaxation occurs via
      beta(2)-AR, and loss of caveolae does not perturb beta(2)-AR function but unmasks
      an additional activation of beta(3)-AR. In contrast, detrusor relaxation in man
      is mediated exclusively via beta(3)-AR.

PMID- 18820137
TI  - Introducing the HRET Patient Safety Fellowship and Action Learning Projects.

PMID- 18820138
TI  - The tipping point: the relationship between volume and patient harm.
AB  - This study purports to show the relationship between volume and patient harm due
      to health care error. Using 5 measures of volume and incident reports weighted
      for patient harm over the course of 515 days, it is shown that increased volume
      is related to increased harm to patients. As the number of areas in the hospital
      experiencing high volume increased, the likelihood of patients sustaining serious
      harm because of health care error also increased. This is attributed to reaching
      system capacity causing support services (ie, lab, pharmacy, radiology,
      housekeeping and engineering) to be overwhelmed and unable to keep up with
      requests from caregivers.

PMID- 18820139
TI  - An innovative method to assess negotiation skills necessary for quality
      improvement.
AB  - Quality improvement (QI) initiatives require leaders who can facilitate change
      through negotiation. Although a few education programs teach these skills, there
      is no published literature on methods to assess competency in negotiation. This
      study's purpose was to determine the psychometric properties of an Objective
      Structured Clinical Examination (OSCE) to assess negotiation skills. The OSCE
      uses an actor trained to respond to the learner in a standardized fashion. The
      negotiation station was part of an 8-station QI OSCE piloted in the Mayo Clinic
      Endocrinology and Preventive Medicine fellowship programs. External experts
      judged the content validity to be excellent. Interrater reliability was
      outstanding for the global competency assessment (0.80) and moderate for
      checklist scores (0.53). All participating faculty strongly agreed (33.3%) or
      agreed (66.7%) that the OSCE station was an authentic assessment tool. Further
      research is needed to study the predictive validity of such an OSCE and its
      application to assessing other quality improvement competencies.

PMID- 18820140
TI  - Clinical ethics and the quality initiative: a pilot study for the empirical
      evaluation of ethics case consultation.
AB  - The Institute of Medicine's quality imperatives include the need to provide safe,
      effective, patient-centered, timely, efficient, and equitable care. Less
      attention has been paid to quality metrics as they relate to the assessment of
      clinical ethics consultation and its impact on care. A better understanding of
      how ethics consultation influences the quality of care might identify
      opportunities for improvement. A descriptive pilot study, involving 7 hospitals
      in the New York-Presbyterian Healthcare System, was conducted to identify key
      elements of the ethics consultative process that might impact clinical and
      psychosocial outcomes. A majority of consults involved medical or intensive care
      unit patients and end-of-life decision making; 75.5% had or received a do-not
      resuscitate order, 90.6% lacked decision-making capacity, 43.4% had an advance
      directive. Conflict existed in a majority. Future research should include
      surrogate decision making, patients on nonmedical services who may have
      unrecognized ethical dilemmas, and the role of conflict in clinical care.

PMID- 18820141
TI  - Resource use and associated care effectiveness results for people with diabetes
      in managed care organizations.
AB  - OBJECTIVE: To examine how resource use varies with care quality for managed care
      populations with diabetes. DESIGN AND METHODS: Data from 31 commercial health
      plans (23 health maintenance organizations and 8 preferred provider
      organizations) were analyzed. Resource use was calculated using medical and
      pharmacy claims and enrollment data for members with diabetes. A standardized
      pricing methodology was applied for resource use associated with inpatient,
      pharmacy, evaluation and management, and procedural services. Quality of care
      results were calculated for 4 process quality indicators of the Healthcare
      Effectiveness Data and Information Set (HEDIS) comprehensive diabetes care
      measure set. RESULTS: Resource use varied more between organizations than quality
      of care results. Pharmacy resource use was significantly associated with higher
      quality; inpatient, procedure and surgery, and ambulatory care visit resource use
      were not significantly associated. CONCLUSIONS: Quality and resource use for
      managed care populations with diabetes may vary considerably and be largely
      independent factors in health care delivery. Health plans may be able to
      favorably impact both factors.

PMID- 18820142
TI  - Quality of lipid management in outpatient care: a national study using electronic
      health records.
AB  - To examine lipid management in a large national outpatient network, a cross
      sectional study was conducted that included 1,385,242 active patients ages 20 to
      79 years of age in a national network of over 5000 providers using electronic
      health records (EHRs). Adequate lipid testing, achievement of lipid goals, and
      appropriate use of lipid-lowering medication were defined according to National
      Cholesterol Education Program (NCEP) guidelines. Lipid testing was adequate for
      62% of high-risk, 67% of moderate-risk, and 36% of low-risk patients. Lipid goals
      were achieved in 65%, 66%, and 90% of these 3 risk groups; 35%, 45%, and 32%
      achieved adequate testing and optimal goals. Medications were appropriately
      prescribed for 70%, 47%, and 48%. There is significant room for improvement in
      lipid management, particularly among high-risk patients. National EHR networks
      are excellent vehicles for large outpatient quality of care studies, particularly
      for measuring clinical outcomes such as lipid levels.

PMID- 18820143
TI  - Innovation in health care: a primer.
AB  - As organizations strive for ways to control health care spending, address the
      growing needs of an aging population, and respond satisfactorily to a more
      informed and demanding consumer base, the opportunities for innovation have
      increased exponentially. By means of this article, the authors describe the basic
      concepts of purposeful innovation, and compare and contrast it to quality
      improvement. The authors also provide an overview of the terminology and types of
      innovation, describe the innovation life cycle, and discuss diffusion and
      commercialization of innovations. This article provides a primer on innovation
      for quality improvement practitioners and physician leaders who play a key role
      in creating innovation and environments for innovations to flourish.

PMID- 18820144
TI  - The quality of qualitative research.
AB  - In general, an appreciation of the standards of qualitative research and the
      types of qualitative data analyses available to researchers have not kept pace
      with the growing presence of qualitative studies in medical science. To help
      rectify this problem, the authors clarify qualitative research reliability,
      validity, sampling, and generalizability. They also provide 3 major theoretical
      frameworks for data collection and analysis that investigators may consider
      adopting. These 3 approaches are ethnography, existential phenomenology, and
      grounded theory. For each, the basic steps of data collection and analysis
      involved are presented, along with real-life examples of how they can contribute
      to improving medical care.

PMID- 18820145
TI  - The quality and disparities reports: why is progress so slow?

PMID- 18820147
TI  - Give the Sahara desert to a health care administrator and a few weeks later he
      will have to import sand.

PMID- 18820148
TI  - Predictors of medication errors.

PMID- 18820150
TI  - ASAS Centennial Paper: The future of teaching and research in companion animal
      biology in departments of animal sciences.
AB  - Departments of animal sciences must be relevant to a society in which a small
      number of people can raise almost all the food animal products needed. The
      declining number of people involved in animal agriculture has decreased
      enrollment of students interested in food animals in many departments of animal
      science. However, several departments welcomed students from a diverse background
      and began research on animals other than food animals. In many states, the
      undergraduate enrollment is made up primarily of students interested only in
      companion animals. A benefit of this is that we have recruited new students into
      animal agriculture and they have gone on to excellent careers. We have a new
      challenge now: how to maintain and expand the efforts in teaching, research, and
      outreach of companion animal science. Departments wishing to expand in teaching
      have examples of successful courses and curricula from other departments. Some
      departments have expanded their teaching efforts across their own university to
      teach about pets to a wider audience than their own majors; other departments can
      follow. In research, a small number of faculty have been able to establish
      extramurally funded projects on pets, including horses. But it will be difficult
      for more than a handful of departments to have a serious research effort in dogs,
      cats, birds, fish, or exotic animals. Departments will have to make a concerted
      effort to invest in such endeavors; joint ventures with other universities and
      colleges of veterinary medicine (or medicine) will probably be required. Funding
      sources for "traditional" efforts in nutrition, reproduction, and physiology are
      small and inconsistent; however, with the progress of the equine, canine, and
      feline genome projects, there should be opportunities from federal funding
      sources aimed at using animal models for human health. In addition, efforts in
      animal behavior and welfare can be expanded, perhaps with some funding from
      private foundations or animal-supportive organizations.

PMID- 18820151
TI  - Dietary plasma proteins, the intestinal immune system, and the barrier functions
      of the intestinal mucosa.
AB  - The intestinal mucosa contributes to homeostasis by preventing the entrance of
      biological and chemical agents across the epithelium that could alter the
      stability of the system. This protective function is especially important at the
      time of weaning, when animals are exposed to infectious agents and to numerous
      stresses such as the change of environment and diet. Diets supplemented with
      spray-dried plasma or plasma protein fractions have been shown to improve growth
      performance of farm animals and have been proposed as an alternative to
      antibiotics. In this review, we summarize our findings on the mechanism of action
      of dietary plasma proteins using a rat model of intestinal inflammation, based on
      the administration of Staphylococcus aureus enterotoxin B (SEB). Staphylococcal
      enterotoxin B activates the gut-associated lymphoid tissue (GALT), increasing T
      lymphocytes in Peyer's patches and the number of activated T lymphocytes in
      mesenteric lymph nodes (organized GALT). In the lamina propria SEB increased
      cytotoxic T gammadelta and natural killer cell populations of the diffuse GALT.
      Staphyloccocal enterotoxin B significantly increased proinflammatory cytokines in
      Peyer's patches and mucosa. Plasma protein supplements modulated the mucosal
      immune response in organized and diffuse GALT, protecting GALT from possible
      excessive activation by the SEB challenge. These effects are accompanied by a
      reduction of proinflammatory cytokine production, supporting the view that
      changes in cytokine production mediate the effects of dietary plasma proteins
      during intestinal inflammation. The increase in mucosal permeability and
      intestinal secretion induced by SEB was associated with decreased expression of
      mucosal tight-junction and adherent-junction proteins. Both plasma and plasma
      protein fractions prevented the effects of SEB on intestinal permeability, thus
      reducing the exposure of the host to microbial and food antigens across the
      interstitial space. These findings indicate that dietary plasma proteins modulate
      functional and structural properties of the intestinal mucosa.

PMID- 18820152
TI  - ASAS centennial paper: Lactation biology for the twenty-first century.
AB  - Knowledge of general aspects of mammary gland function, including metabolic
      pathways and hormonal regulation of mammary gland development and lactation, in
      livestock species was obtained several decades ago. As basic biological
      information of growth factor action, apoptotic mechanisms, and signal
      transduction events has exploded, the mouse became the model of choice for
      studying fundamental mechanisms regulating mammary function. A complete sequenced
      genome also has made the mouse amenable for studies of mammary gene network
      expression. Advances in molecular biology techniques currently allow researchers
      to genetically modify mice to either overexpress or completely lack specific
      genes, thereby studying their function in an in vivo setting. Furthermore, the
      use of mammary-specific promoters has allowed genes related to mammary gland
      function to be eliminated from the mammary gland in a developmental and tissue
      specific manner. These studies have demonstrated the complexity that underlies
      mammary gland development and function in rodents and may provide insight into
      the mechanisms that ultimately allow the ruminant or swine mammary gland to
      function in a coordinated fashion throughout puberty, pregnancy, lactation, and
      involution. The challenge facing animal scientists is how to obtain similar
      information in much larger and expensive livestock. One possible approach is to
      manipulate gene expression in vitro using mammary cell culture models derived
      from domestic animals (e.g., genes can be "knocked down" using small interfering
      RNA approaches). Ultimately, major advances in understanding lactation biology
      may come from coupling basic mechanistic information with functional genomics,
      proteomics, and metabolomics approaches. A strong foundation in bioinformatics
      will also be required to optimize use of these new technologies. Stem cell
      biology also represents an exciting area in the next decade that holds promise
      for improving lactation efficiency. Strong training of our future scientists in
      these areas should facilitate livestock-focused mammary gland research that will
      allow basic information to be gained at unprecedented amounts, ultimately leading
      to optimization of livestock production.

PMID- 18820153
TI  - Transporters in the absorption and utilization of zinc and copper.
AB  - Before the discovery and elucidation of transporters, mammals were thought to
      cotransport Cu or Zn as an anionic complex, such as binding with an AA as a
      chelate or a receptor such as transferrin. In 1995, the first mammalian Zn
      transporter (ZnT) gene, ZnT1, was identified. However, 2 protein families are now
      thought to be involved in Zn transport. The ZnT family reduces intracellular Zn
      by aiding in efflux from the cell or promoting the influx into intracellular
      vesicles. The mechanism of ZnT transport against a Zn concentration gradient is
      unknown; however, only ZnT1 appears to be located at the plasma membrane. It has
      been shown to respond in tissues in a variety of ways to Zn reduction and
      supplementation. In our laboratory, we have found ZnT1 and metallothionein to
      work in concert during pharmacological Zn supplementation. The second protein
      family, Zip proteins, provides Zn transport from extracellular fluid or
      intracellular vesicles into the cytoplasm and has not been identified in a
      livestock species. Like Zn, no good indicator of status has been identified for
      Cu. However, the recent identification of Cu transporters and chaperones gives
      researchers the opportunity to understand the regulation of Cu trafficking where
      the proteins are modified by posttranslational mechanisms. Two Cu transporters,
      Ctr1 and Ctr3, mediate high-affinity Cu uptake. A small cytoplasmic protein,
      MURR1, has been identified in human hepatic tissue, but its role in Cu metabolism
      is unknown. The discovery of Cu chaperones that are involved in facilitating Cu
      absorption into proteins may provide an excellent status indicator. It has been
      shown that the Cu chaperone for Cu/Zn superoxide dismutase (CCS) is increased in
      tissue of Cu-deficient rats, induced when moderately high Zn diets are fed. We
      have recently found CCS in the young pig. Other Cu chaperone proteins that have
      been identified are COX17 and Atox1. As with CCS, they are involved in making Cu
      available to apo-enzymes inside the cell. It is essential that these new
      molecular findings be used to evaluate the bioavailability of and nutritional
      need for Cu and Zn in livestock.

PMID- 18820154
TI  - Recent advances in modeling nutrient utilization in ruminants.
AB  - Mathematical modeling techniques have been applied to study various aspects of
      the ruminant, such as rumen function, postabsorptive metabolism, and product
      composition. This review focuses on advances made in modeling rumen fermentation
      and its associated rumen disorders, and energy and nutrient utilization and
      excretion with respect to environmental issues. Accurate prediction of
      fermentation stoichiometry has an impact on estimating the type of energy
      yielding substrate available to the animal, and the ratio of lipogenic to
      glucogenic VFA is an important determinant of methanogenesis. Recent advances in
      modeling VFA stoichiometry offer ways for dietary manipulation to shift the
      fermentation in favor of glucogenic VFA. Increasing energy to the animal by
      supplementing with starch can lead to health problems such as subacute rumen
      acidosis caused by rumen pH depression. Mathematical models have been developed
      to describe changes in rumen pH and rumen fermentation. Models that relate rumen
      temperature to rumen pH have also been developed and have the potential to aid in
      the diagnosis of subacute rumen acidosis. The effect of pH has been studied
      mechanistically, and in such models, fractional passage rate has a large impact
      on substrate degradation and microbial efficiency in the rumen and should be an
      important theme in future studies. The efficiency with which energy is utilized
      by ruminants has been updated in recent studies. Mechanistic models of N
      utilization indicate that reducing dietary protein concentration, matching
      protein degradability to the microbial requirement, and increasing the energy
      status of the animal will reduce the output of N as waste. Recent mechanistic P
      models calculate the P requirement by taking into account P recycled through
      saliva and endogenous losses. Mechanistic P models suggest reducing current P
      amounts for lactating dairy cattle to at least 0.35% P in the diet, with a
      potential reduction of up to 1.3 kt/yr. A model that integrates nutrient
      utilization and health has great potential benefit for ruminant nutrition
      research. Finally, whole-animal or farm level models are discussed. An example
      that used a multiple-criteria decision-making framework is reviewed, and the
      approach is considered to be appropriate in dealing with the multidimensional
      nature of agricultural systems and can be applied to assist the decision process
      in cattle operations.

PMID- 18820155
TI  - ASAS Centennial Paper: Future needs of research and extension in forage
      utilization.
AB  - Forage-animal production agriculture is implementing infrastructure changes and
      management strategies to adjust to increased energy-related costs of fuel, feed
      grains, fertilizers, and seeds. The primary objectives of this position paper are
      to assess future research and extension scientific needs in forage utilization,
      financial support for the discipline, and changing status and number of
      scientists. A survey questionnaire returned from 25 land-grant universities in
      the eastern half of the United States rated the top 4 research needs as 1)
      pasture systems and efficiency of production; 2) interfacing with energy
      concerns; 3) forage cultivar evaluations and persistence; and 4) environment
      impacts. Plant-animal future research needs at 11 USDA-ARS regional locations are
      targeted at sustainable management and improved livestock performance,
      ecophysiology and ecology of grasslands, environment impacts, and improved
      technologies for nutritive value assessments. Extension scientists from 17
      southern and northeastern states listed the top 3 needs as forage persistence,
      soil fertility and nutrient management, and pasture systems and efficiency of
      production. Grant funds currently provide more than 40% of land-grant university
      research and extension efforts in forage utilization, and scientists estimate
      that this support base will increase to 55 to 60% of the funding total by 2013.
      Reduced allocation of state and federal funding has contributed to a reduction in
      the number of full-time equivalent (FTE) scientists engaged in forage utilization
      research and extension activities. The current 25 state FTE conducting research
      number about 2.8 per state. This includes 10 states with >3, 11 states with <2,
      and 3 states with <1 FTE. Increased interest in cellulosic energy, climate
      change, and environmental impact may offer new opportunities for these FTE to
      participate in integrated cross-discipline research Extension programming, and
      technology transfer methods will change to accommodate reduced funding but with
      increasing numbers of novice, recreation-oriented landowners.

PMID- 18820156
TI  - Myosin heavy chain isoform content and energy metabolism can be uncoupled in pig
      skeletal muscle.
AB  - Genetic selection for improved growth and overall meatiness has resulted in the
      occurrence of 2 major mutations in pigs, the Rendement Napole (RN) and Halothane
      (Hal) gene mutations. At the tissue level, these mutations influence energy
      metabolism in skeletal muscle and muscle fiber type composition, yet also
      influence total body composition. The RN mutation affects the adenosine
      monophosphate-activated protein kinase gamma subunit and results in increased
      glycogen deposition in the muscle, whereas the Hal mutation alters sarcoplasmic
      calcium release mechanisms and results in altered energy metabolism. From a meat
      quality standpoint, these mutations independently influence the extent and rate
      of muscle energy metabolism postmortem, respectively. Even though these mutations
      alter overall muscle energy metabolism and histochemically derived muscle fiber
      type independently, their effects have not been yet fully elucidated in respect
      to myosin heavy chain (MyHC) isoform content and those enzymes responsible for
      defining energetics of the tissue. Therefore, the objective of this study was to
      determine the collective effects of the RN and Hal genes on genes and gene
      products associated with different muscle fiber types in pig skeletal muscle. To
      overcome potential pitfalls associated with traditional muscle fiber typing, real
      time PCR, gel electrophoresis, and Western blotting were used to evaluate MyHC
      composition and several energy-related gene expressions in muscles from wild
      type, RN, Hal, and Hal-RN mutant pigs. The MyHC mRNA levels displayed sequential
      transitions from IIb to IIx and IIa in pigs bearing the RN mutation. In addition,
      our results showed MyHC protein isoform abundance is correlated with mRNA level
      supporting the hypothesis that MyHC genes are transcriptionally controlled.
      However, transcript abundance of genes involved in energy metabolism, including
      lactate dehydrogenase, citrate synthase, glycogen synthase, and peroxisome
      proliferator-activated receptor alpha, was not different between genotypes. These
      data show that the RN and Hal gene mutations alter muscle fiber type composition
      and suggest that muscle fiber energy metabolism and speed of contraction, the 2
      determinants of muscle fiber type, can be uncoupled.

PMID- 18820157
TI  - Effects of implanting and feeding zilpaterol hydrochloride on performance,
      carcass characteristics, and subprimal beef yields of fed cows.
AB  - Sixty crossbred cull cows were used to determine the combined effects of a
      trenbolone acetate-estradiol implant and feeding zilpaterol hydrochloride on
      performance, carcass characteristics, and subprimal yields of mature cows fed for
      70 d. Cows were assigned to 1 of 5 treatments: 1) grazing native grass pasture
      (G); 2) concentrate-fed (C) a grain sorghum-sorghum silage diet; 3) concentrate
      fed and implanted (CI) with Revalor-200 (trenbolone acetate-estradiol); 4)
      concentrate-fed and fed Zilmax (zilpaterol hydrochloride) beginning on d 38 of
      the feeding period (CZ); and 5) concentrate-fed, implanted, and fed Zilmax
      beginning on d 38 (CIZ). The concentrate diet consisted primarily of ground grain
      sorghum and sorghum silage. During the last 34 d of the feeding trial,
      concentrate-fed (C, CI, CZ, and CIZ) cows had greater (P < 0.05) gains than G
      cows. Hot carcass weights and dressing percentages were greater (P < 0.05) for
      the concentrate-fed cows than for G cows. Longissimus muscle area was largest (P
      < 0.05) for CIZ cows, whereas subprimal weights from the chuck were heavier (P <
      0.05) from CIZ cows than C and G cows, and carcasses from CI and CZ cows had
      heavier (P < 0.05) chuck subprimal weights than G cows. Rib and round subprimal
      weights were heavier (P < 0.05) for concentrate-fed cows compared with G cows. In
      addition, carcasses from CIZ cows had heavier (P < 0.05) total subprimal weights,
      and total subprimals were a greater percentage of their initial BW than C cows.
      Rib cut-out and total soft tissue weights from the 9-10-11th rib were less (P <
      0.05) for G cows than concentrate-fed cows. Feeding cull cows a concentrate diet
      increased carcass weight, dressing percentage, and subprimal yields compared with
      feeding cows a grass-based pasture diet, and the combination of a trenbolone
      acetate-estradiol implant and feeding zilpaterol hydrochloride can maximize
      trimmed beef yields from cull cows fed a high-concentrate diet.

PMID- 18820158
TI  - Management of mastitis on organic and conventional dairy farms.
AB  - This paper compares management of mastitis on organic dairy farms with that on
      conventional dairy farms. National standards for organic production vary by
      country. In the United States, usage of antimicrobials to treat dairy cattle
      results in permanent loss of organic status of the animal, effectively limiting
      treatment choices for animals experiencing bacterial diseases. There are no
      products approved by the US Food and Drug Administration that can be used for
      treatment of mastitis on organic dairy farms, and usage of unapproved products is
      contrary to Food and Drug Administration guidelines. In general, organic dairy
      farms tend to be smaller, produce less, and more likely to be housed and milked
      in traditional barns as compared with conventionally managed herds. It is
      difficult to compare disease rates between herds managed conventionally or
      organically because perception and detection of disease is influenced by
      management system. To date, no studies have been published with the defined
      objective of comparing animal health on organic dairy herds with that on
      conventional dairy herds in the United States. European studies have not
      documented significant differences in animal health based on adoption of organic
      management. Few differences in bulk tank somatic cell counts have been identified
      between organic and conventional herds. Farmers that have adopted organic
      management consistently report fewer cases of clinical mastitis, but organic
      farmers do not use the same criteria to detect clinical mastitis. European dairy
      farmers that adopt organic management report use of a variety of conventional and
      alternative therapies for treatment and control of mastitis. In the United
      States, organic farmers treat clinical mastitis using a variety of alternative
      therapies including whey-based products, botanicals, vitamin supplements, and
      homeopathy. Organic farmers in the United States use a variety of alternative
      products to treat cows at dry-off. Virtually no data are available that support
      the clinical efficacy of any of the alternative veterinary products used for
      treatment or prevention of mastitis. Some associations between organic management
      and antimicrobial susceptibility of gram-positive mastitis pathogens have been
      noted, but overall, few mastitis pathogens from both conventional and organic
      dairy herds demonstrate resistance to antibiotics commonly used for mastitis
      control.

PMID- 18820159
TI  - Dietary conjugated linoleic acid changes belly and bacon quality from pigs fed
      varied lipid sources.
AB  - The objective of this experiment was to determine the effects of dietary lipid
      source with or without the addition of CLA on bacon composition and quality.
      Forty-eight barrows at a beginning BW of 55 kg +/- 2.2 were fed 1 of 6 diets for
      56 d. These diets consisted of: 1) normal corn (NC), 2) NC + 1.25% CLA-60 oil (NC
      + CLA), 3) high-oil corn (HOC), 4) HOC + 1.25% CLA-60 oil (HOC-CLA), 5) NC +
      choice white grease (CWG; NC + CWG), and 6) NC + CWG + 1.25% CLA-60 oil (NC + CWG
      + CLA). The CLA-60 contains 60% CLA isomers in the oil, and therefore, 1.25% oil
      was needed to achieve 0.75% CLA in the diet. Soy oil replaced CLA in control
      diets. Choice white grease and high-oil corn were selected as fat sources for
      this study because of their utility in energy density for growing-finishing pigs,
      especially in hot weather. Pigs were slaughtered at an average BW of 113 kg +/-
      4.1, and carcasses were fabricated at 24 h postmortem. Statistical analysis was
      performed using the mixed model procedure of SAS, and the main effects tested
      were dietary lipid source, CLA, and 2-way interaction. The addition of CLA to
      each basal diet improved (P < 0.05) belly firmness measured either lean side down
      or fat side down from the belly bar firmness test [4.39 cm vs. 7.01 cm (lean
      down) and 5.75 cm vs. 10.54 cm (fat down)] for 0 and 0.75% dietary CLA,
      respectively. The compression test used on bacon slabs showed that bacon from CLA
      supplemented pigs was approximately 20% firmer than that from controls. Pigs fed
      the HOC diets had softer bellies compared (P < 0.05) with pigs fed the NC diet as
      measured by the belly bar test [6.94 cm vs. 9.26 cm (fat down)], respectively.
      Conjugated linoleic acid did not, however, improve bacon sliceability. No
      differences were observed for moisture, protein, or lipid percentages between any
      treatments. Overall, there was a CLA effect (P < 0.04) for lipid oxidation, in
      which the addition of CLA decreased bacon oxidation (0.1498 CLA vs. 0.1638 no
      CLA). Dietary CLA increased the percentage of SFA in tissues from pigs
      supplemented with CLA. Dietary inclusion of CLA increased the concentration of
      all measured isomers of CLA in bacon. Sensory scores of bacon showed no
      differences for any of the sensory attributes measured between any of the
      treatments. Our results indicate that inclusion of dietary CLA will improve belly
      firmness, extend the shelf life stability of bacon, and increase the degree of
      fat saturation.

PMID- 18820160
TI  - Effect of a single dose of dexamethasone on glucose homeostasis in healthy horses
      by using the combined intravenous glucose and insulin test.
AB  - Sustained dexamethasone administration to horses results in insulin resistance,
      which may predispose them to laminitis. A single dose of dexamethasone is
      commonly used as a diagnostic aid, yet the effect of a single dose of
      dexamethasone on glucose homeostasis in horses is not well defined. The objective
      of this study was to characterize the change in glucose dynamics over time in
      response to a single dose of dexamethasone. A combined glucose-insulin tolerance
      test (CGIT) was performed on 6 adult geldings before and at 2, 24, and 72 h
      postdexamethasone (40 microg/kg of BW, i.v.); a minimum of 1 wk of rest was
      allowed between treatments. Before any treatment, the CGIT resulted in a
      hyperglycemic phase followed by a hypoglycemic phase. Dexamethasone affected
      glucose dynamics in 3 ways: 1) at 2 h, dexamethasone shortened the ascending
      branch of the negative phase (P < 0.001) of the test, indicating moderate insulin
      resistance; 2) at 24 h, dexamethasone impaired glucose clearance by extending the
      positive phase and eliminating the negative phase while insulin was elevated
      before the CGIT, indicating a decreased response to insulin; and 3) at 72 h,
      dexamethasone caused a deeper nadir value (P < 0.001) compared with
      predexamethasone, indicating an increased response to insulin. It was concluded
      that dexamethasone decreased the response to insulin as early as 2 h and
      maximally at 24 h. At 72 h, dexamethasone caused an increased response to
      insulin, which was unexpected.

PMID- 18820161
TI  - Gene expression patterns during intramuscular fat development in cattle.
AB  - Deposition of intramuscular fat, or "marbling," in beef cattle contributes
      significantly to meat quality variables, including juiciness, flavor, and
      tenderness. The accumulation of intramuscular fat is largely influenced by the
      genetic background of cattle, as well as their age and nutrition. To identify
      genes that can be used as early biomarkers for the prediction of marbling
      capacity, we studied the muscle transcriptome of 2 cattle crossbreeds with
      contrasting intramuscular fat content. The transcriptomes of marbling LM tissue
      of heifers from Wagyu x Hereford (WxH; n = 6) and Piedmontese x Hereford (PxH; n
      = 7) crosses were profiled by using a combination of complementary DNA microarray
      and quantitative reverse transcription-PCR. Five biopsies of LM were taken from
      each animal at approximately 3, 7, 12, 20, and 25 mo from birth. Tissue was also
      collected from the LM of each animal at slaughter (approximately 30 mo).
      Microarray experiments, conducted on the first 3 biopsies of 2 animals from each
      crossbreed, identified 97 differentially expressed genes. The gene expression
      results indicated that the LM transcriptome of animals with high marbling
      potential (WxH) could be reliably distinguished from less marbled animals (PxH)
      when the animals were as young as 7 mo of age. At this early age, one cannot
      reliably determine meaningful differences in intramuscular fat deposition. We
      observed greater expression of a set of adipogenesis- and lipogenesis-related
      genes in the LM of young WxH animals compared with their PxH contemporaries. In
      contrast, genes highly expressed in PxH animals were associated with
      mitochondrial oxidative activity. Further quantitative reverse transcription-PCR
      experiments revealed that the messenger RNA of 6 of the lipogenesis-related genes
      also peaked at the age of 20 to 25 mo in WxH animals. The messenger RNA
      expression of ADIPOQ, SCD, and THRSP was highly correlated with intramuscular fat
      content of an individual in WxH animals. Our study provides clear evidence of
      early molecular changes associated with marbling and also identifies specific
      time frames when intramuscular fat development in cattle muscle can be detected
      by using gene expression. This information could be used by animal scientists to
      design optimal nutrition for high marbling potential. In addition, the genes
      found to be highly expressed during development of marbling could be used to
      develop genetic markers or biomarkers to assist with beef production strategies.

PMID- 18820162
TI  - Plasma metabolites of receiving heifers and the relationship between apparent
      bovine respiratory disease, body weight gain, and carcass characteristics.
AB  - Six hundred sixty-five crossbred beef heifers initially weighing 225 kg were used
      in a completely randomized design to measure plasma glucose, lactate, and urea N
      concentrations at time of initial processing, determine the incidence of apparent
      bovine respiratory disease (BRD) in receiving cattle, and evaluate the effect of
      apparent BRD on subsequent cattle growth and carcass characteristics. Heifers
      were processed within 24 h of arrival, and processing included vaccination
      against common viral and clostridial diseases, recording rectal temperature, and
      sampling whole blood for subsequent measurement of plasma glucose, lactate, and
      urea concentrations. Heifers were monitored for clinical signs of apparent BRD,
      including depression, lethargy, anorexia, coughing, rapid breathing, and nasal or
      ocular discharge. Heifers exhibiting signs of apparent BRD received antibiotic
      therapy, and the number of times a heifer was treated for apparent BRD was
      recorded. Following the 36-d receiving period, heifers were transported to native
      grass pastures and allowed to graze for 136 d. At the end of the grazing season,
      heifers were transported to a commercial feedlot where they were adapted to a
      common finishing diet offered for ad libitum consumption. Following the 124-d
      finishing period, heifers were slaughtered and carcass data were collected.
      Heifers treated for apparent BRD had decreased plasma glucose (linear, P < 0.01),
      lactate (linear, P < 0.01), and urea N concentrations (linear, P < 0.06) measured
      at time of initial processing. Rectal temperature measured at time of initial
      processing tended to be greater (linear, P < 0.11) for heifers treated for
      apparent BRD. Heifers treated for apparent BRD during the receiving period had
      decreased overall ADG (linear, P < 0.10), final BW (linear, P < 0.01), HCW
      (linear, P < 0.01), fat thickness (linear, P < 0.01), and marbling score (linear,
      P < 0.03). These data suggest that initial plasma glucose and lactate
      concentrations might be affected by the health status of receiving cattle and
      that increased incidence of apparent BRD in cattle decreases ADG and carcass
      quality.

PMID- 18820163
TI  - Influence of slow-release urea on nitrogen balance and portal-drained visceral
      nutrient flux in beef steers.
AB  - Two experiments were conducted to evaluate the effects of slow-release urea (SRU)
      versus feed-grade urea on portal-drained visceral (PDV) nutrient flux, nutrient
      digestibility, and total N balance in beef steers. Multi-catheterized steers were
      used to determine effects of intraruminal dosing (Exp. 1; n = 4; 319 +/- 5 kg of
      BW) or feeding (Exp. 2; n = 10; 4 Holstein steers 236 +/- 43 kg of BW and 6 Angus
      steers 367 +/- 46 kg of BW) SRU or urea on PDV nutrient flux and blood variables
      for 10 h after dosing. Intraruminal dosing of SRU (Exp. 1) prevented the rapid
      increase in ruminal ammonia concentrations that occurred with urea dosing
      (treatment x time P = 0.001). Although apparent total tract digestibilities of
      DM, OM, NDF, and ADF were not affected by treatment (P > 0.53, Exp. 2), SRU
      increased fecal N excretion (49.6 vs. 45.6 g/d; P = 0.04) and reduced apparent
      total tract N digestibility (61.7 vs. 66.0%; P = 0.003). Transfer of urea from
      the blood to the gastrointestinal tract occurred for both treatments in Exp. 1
      and 2 at all time points with the exception for 0.5 h after dosing of urea in
      Exp. 1, when urea was actually transferred from the gastrointestinal tract to the
      blood. In both Exp. 1 and 2, both urea and SRU treatments increased arterial urea
      concentrations from 0.5 to 6 h after feeding, but arterial urea concentrations
      were consistently less with SRU (treatment x time P < 0.001, Exp. 1; P = 0.007,
      Exp. 2). Net portal ammonia release remained relatively consistent across the
      entire sampling period with SRU treatment, whereas urea treatment increased
      portal ammonia release in Exp. 1 and tended to have a similar effect in Exp. 2
      (treatment x time P = 0.003 and P = 0.11, respectively). Urea treatment also
      increased hepatic ammonia uptake within 0.5 h (treatment x time P = 0.02, Exp.
      1); however, increased total splanchnic release of ammonia for the 2 h after urea
      treatment dosing suggests that PDV ammonia flux may have exceeded hepatic
      capacity for removal. Slow-release urea reduces the rapidity of ammonia-N release
      and may reduce shifts in N metabolism associated with disposal of ammonia.
      However, SRU increased fecal N excretion and increased urea transfer to the
      gastrointestinal tract, possibly by reduced SRU hydrolysis or effects on
      digestion patterns. Despite this, the ability of SRU to protect against the
      negative effects of urea feeding may be efficacious in some feeding applications.

PMID- 18820164
TI  - Effects of slow-release urea on ruminal digesta characteristics and growth
      performance in beef steers.
AB  - Two experiments were conducted to evaluate the effects of slow-release urea (SRU)
      versus feed-grade urea on ruminal metabolite characteristics in steers and DMI,
      gain, and G:F in growing beef steers. Experiment 1 used 12 ruminally cannulated
      steers (529 +/- 16 kg of BW) to monitor the behavior of SRU in the ruminal
      environment. Compared with feed-grade urea, SRU decreased ruminal ammonia
      concentration (P = 0.02) and tended to increase ruminal urease activity (P =
      0.06) without affecting ruminal VFA molar proportions or total concentrations (P
      > 0.20). After 35 d of feeding, the in situ degradation rate of SRU was not
      different between animals fed urea or SRU (P = 0.48). Experiment 2 used 180 Angus
      cross steers (330 +/- 2.3 kg) fed corn silage-based diets supplemented with urea
      or SRU for 56 d to evaluate the effects on feed intake, gain, and G:F. The design
      was a randomized complete block with a 2 x 4 + 1 factorial arrangement of
      treatments. Treatments included no supplemental urea (control) or urea or SRU at
      0.4, 0.8, 1.2, or 1.6% of diet DM. Over the entire 56 d experiment, there were
      interactions of urea source x concentration for gain (P = 0.04) and G:F (P =
      0.01) because SRU reduced ADG and G:F at the 0.4 and 1.6% supplementation
      concentrations but was equivalent to urea at the 0.8 and 1.2% supplementation
      concentrations; these effects were due to urea source x concentration
      interactions for gain (P = 0.06) and G:F (P = 0.05) during d 29 to 56 of the
      experiment. The SRU reduced DMI during d 29 to 56 (P = 0.01) but not during d 0
      to 28, so that over the entire experiment there was no difference in DMI for urea
      source (P = 0.19). These collective results demonstrate that SRU releases N
      slowly in the rumen with no apparent adaptation within 35 d. Supplementation of
      SRU may limit N availability at low (0.4%) concentrations but is equivalent to
      urea at 0.8 and 1.2% concentrations.

PMID- 18820165
TI  - Detection of bovine leukocyte antigen DRB3 alleles as candidate markers for
      clinical mastitis resistance in Holstein x Zebu.
AB  - Bovine leukocyte antigen DRB3 alleles from Holstein x Zebu crossbred dairy cows
      (n = 409) were analyzed using the PCR-RFLP technique. Exon II of DRB3 was
      amplified using locus-specific primers (HLO30/HLO32), followed by digestion with
      3 restriction enzymes (RsaI, BstyI, and HaeIII). Forty alleles were found with
      frequency ranging from 0.005 to 0.139. The most frequently detected alleles of
      Holstein x Zebu were DRB3*16, *51, *23, *11, *8, and *1, accounting for 61.12% of
      the alleles in the population. Detection of candidate alleles for clinical
      mastitis occurrence was performed by logistic regression. It was found that
      percentage of Holstein fraction in crossbred cows had a nonsignificant effect (P
      > 0.05). However, parity had a significant effect on mastitis occurrence. In
      addition, DRB3*1 and *52 were the most associated with the occurrence of clinical
      mastitis, whereas *15, *51, and *22 were associated with resistance in crossbred
      populations. This is the first report of association of DRB3*15 and *51 with
      mastitis resistance. The association was validated by examining the candidate
      alleles in another commercial population. Highly susceptible (n = 43) and
      resistant (n = 42) groups of Holstein x Zebu cows were investigated. The result
      confirmed that DRB3*1 and *52 could be considered as susceptibility alleles,
      whereas *15, *51, and *22 could be considered as resistant alleles in Holstein x
      Zebu raised under tropical conditions. In addition, allele effects on 305-d milk
      production were estimated by BLUP. It was shown that most alleles associated with
      high clinical mastitis occurrence were related to increased milk yield. This
      study revealed that allele DRB3*10 had the greatest effect on increasing milk
      yield with moderate resistance to clinical mastitis, which could be used as a
      potential marker for selection in dairy genetic evaluation.

PMID- 18820166
TI  - Editorial: "Brain drain" and loss of resources jeopardize the continued use of
      domestic animals for agricultural and biomedical research.

PMID- 18820167
TI  - ASAS centennial paper: net energy systems for beef cattle--concepts, application,
      and future models.
AB  - Development of nutritional energetics can be traced to the 1400s. Lavoisier
      established relationships among O(2) use, CO(2) production and heat production in
      the late 1700s, and the laws of thermodynamics and law of Hess were discovered
      during the 1840s. Those discoveries established the fundamental bases for
      nutritional energetics and enabled the fundamental entity ME = retained energy +
      heat energy to be established. Objectives became: 1) to establish relationships
      between gas exchange and heat energy, 2) to devise bases for evaluation of foods
      that could be related to energy expenditures, and 3) to establish causes of
      energy expenditures. From these endeavors, the basic concepts of energy
      partitioning by animals were developed, ultimately resulting in the development
      of feeding systems based on NE concepts. The California Net Energy System,
      developed for finishing beef cattle, was the first to be based on retained energy
      as determined by comparative slaughter and the first to use 2 NE values (NE(m)
      and NE(g)) to describe feed and animal requirements. The system has been
      broadened conceptually to encompass life cycle energy requirements of beef cattle
      and modified by the inclusion of numerous adjustments to address factors known to
      affect energy requirements and value of feed to meet those needs. The current NE
      system remains useful but is empirical and static in nature and thus fails to
      capture the dynamics of energy utilization by diverse animals as they respond to
      changing environmental conditions. Consequently, efforts were initiated to
      develop dynamic simulation models that captured the underlying biology and thus
      were sensitive to variable genetic and environmental conditions. Development of a
      series of models has been described to show examples of the conceptual evolution
      of dynamic, mechanistic models and their applications. Generally with each new
      system, advances in prediction accuracy came about by adding new terms to
      conceptually validated models. However, complexity of input requirements often
      limits general use of these larger models. Expert systems may be utilized to
      provide many of the additional inputs needed for application of the more complex
      models. Additional information available from these systems is expected to result
      in an ever-increasing range of application. These systems are expected to have
      increased generality and the capability to be integrated with other models to
      allow economic evaluation. This will eventually allow users to compute solutions
      that allow development of optimal production strategies.

PMID- 18820169
TI  - Preserving the sacred bond: an audit must be performed.

PMID- 18820170
TI  - Untreated patients in "CT screening for lung cancer: update 2007".

PMID- 18820172
TI  - 2008 Focused update incorporated into the ACC/AHA 2006 guidelines for the
      management of patients with valvular heart disease: a report of the American
      College of Cardiology/American Heart Association Task Force on Practice
      Guidelines (Writing Committee to Revise the 1998 Guidelines for the Management of
      Patients With Valvular Heart Disease): endorsed by the Society of Cardiovascular
      Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and
      Society of Thoracic Surgeons.

PMID- 18820173
TI  - The American Heart Association's 2008 Statement of Principles for Healthcare
      Reform.

PMID- 18820174
TI  - The cytolytic enzymes granyzme A, granzyme B, and perforin: expression patterns,
      cell distribution, and their relationship to cell maturity and bright CD57
      expression.
AB  - Cytolytic enzymes (CEs) are critical mediators of anti-viral and -tumor immunity;
      however, as a number of molecules belong to this enzyme family, our understanding
      of CEs remains limited. Specifically, it remains unclear what combinations of
      granzymes and perforin (Perf) are expressed by various immune cells and how CE
      content relates to cellular differentiation. Using polychromatic flow cytometry,
      we simultaneously measured expression of the most common human CEs [granzyme A
      (gA), granzyme B (gB), and Perf] alongside markers of alphabeta and gammadelta T
      cell maturation (CD45RO, CCR7, CD27, CD57). Additionally, we measured CE content
      in NK cell subsets (defined by their expression of CD16 and CD56). We found that
      among a wide variety of immune cells, CE content was linked to cellular maturity.
      Moreover, common expression patterns were shared across cell types, such that gB+
      cells always contained gA, and Perf+ cells were primarily gA+ gB+. Most
      importantly, CD57 expression correlated strongly with simultaneous expression of
      gA, gB, and Perf. Thus, the use of CD57 provides a means to easily isolate viable
      cells with high cytolytic potential, without the need for lethal
      fixation/permeabilization techniques.

PMID- 18820176
TI  - Don't forget the vitamin A when working with its carrier protein.

PMID- 18820175
TI  - Chronic ethanol induces inhibition of antigen-specific CD8+ but not CD4+
      immunodominant T cell responses following Listeria monocytogenes inoculation.
AB  - Chronic ethanol consumption results in immunodeficiency. Previous work with
      chronic ethanol-fed mice has shown reduced splenic weight and cellularity,
      including reduced numbers of CD8+ T cells. However, antigen-specific CD8+ and
      CD4+ T cell responses in chronic ethanol-fed mice have been studied relatively
      little. We have used an attenuated Listeria monocytogenes strain DPL 1942 (LM
      DeltaactA) to inoculate mice and subsequently used CD4+ and CD8+ immunodominant
      peptides of LM to measure the CD4+ and CD8+ T cell responses after chronic
      ethanol exposure. We found no major differences between control and ethanol-fed
      mice in the kinetics and persistence of antigen-specific CD4+ T cells in response
      to an immunodominant LM peptide, as measured by intracellular IFN-gamma staining.
      In contrast to CD4+ responses, three methods of in vitro antigen presentation
      indicated that the primary response of CD8+ T cells to several different epitopes
      was reduced significantly in mice chronically fed ethanol. Antigen-specific CD8+
      T cells were also reduced in chronic ethanol-fed mice during the contraction
      phase of the primary response, and memory cells evaluated at 29 and 60 days after
      inoculation were reduced significantly. BrdU proliferation assays showed that in
      vivo proliferation of CD8+ T cells was reduced in ethanol-fed mice, and IL-2
      dependent in vitro proliferation of naive CD8+ T cells was also reduced. In
      conclusion, these results suggest that antigen-specific CD4+ T cell responses to
      LM are affected little by chronic ethanol consumption; however, antigen-specific
      CD8+ T cell responses are reduced significantly, as are in vivo and in vitro
      proliferation. The reduction of antigen-specific CD8+ T cells may contribute
      strongly to the immunodeficiency caused by ethanol abuse.

PMID- 18820177
TI  - Induction into the Hall of Fame: tracing the lineage of Spemann's organizer.
AB  - The grafting experiments of Spemann and Mangold have been a textbook classic for
      years, but as with many conclusions from experimental embryology, the idea that
      the dorsal lip of the blastopore ;organized' the early patterning of the embryo
      has sometimes come under question. In their 1983 paper in JEEM, Smith and Slack
      extended these classical experiments in newts to the now-standard amphibian model
      Xenopus laevis. By using injected lineage tracers, they distinguished the fates
      of graft and host, and showed unambiguously that the organizer is responsible for
      neural induction and that it dorsalizes the mesoderm.

PMID- 18820178
TI  - Anterior-posterior graded response to Otx2 controls proliferation and
      differentiation of dopaminergic progenitors in the ventral mesencephalon.
AB  - Meso-diencephalic dopaminergic (mdDA) neurons control voluntary movement,
      cognition and the reward response, and their degeneration is associated with
      Parkinson's disease (PD). Prospective cell transplantation therapies for PD
      require full knowledge of the developmental pathways that control mdDA
      neurogenesis. We have previously shown that Otx2 is required for the
      establishment of the mesencephalic field and molecular code of the entire ventral
      mesencephalon (VM). Here, we investigate whether Otx2 is a specific determinant
      of mesencephalic dopaminergic (mesDA) neurogenesis by studying mouse mutants that
      conditionally overexpress or lack Otx2. Our data show that Otx2 overexpression in
      the VM causes a dose-dependent and selective increase in both mesDA progenitors
      and neurons, which correlates with a remarkable and specific enhancement in the
      proliferating activity of mesDA progenitors. Consistently, lack of Otx2 in the VM
      specifically affects the proliferation of Sox2+ mesDA progenitors and causes
      their premature post-mitotic transition. Analysis of the developmental pathway
      that controls the differentiation of mesDA neurons shows that, in the absence of
      Otx2, the expression of Lmx1a and Msx1, and the proneural genes Ngn2 and Mash1 is
      not activated in Sox2+ mesDA progenitors, which largely fail to differentiate
      into Nurr1+ mesDA precursors. Furthermore, proliferation and differentiation
      abnormalities exhibit increasing severity along the anterior-posterior (AP) axis
      of the VM. These findings demonstrate that Otx2, through an AP graded effect, is
      intrinsically required to control proliferation and differentiation of mesDA
      progenitors. Thus, our data provide new insights into the mechanism of mesDA
      neuron specification and suggest Otx2 as a potential target for cell replacement
      based therapeutic approaches in PD.

PMID- 18820180
TI  - Addressing the attitudes of service providers: increasing access to professional
      midwifery care in Nepal.
AB  - Increasing access to professional care during labour and delivery is the central
      strategy in Nepal's commitment to reducing its maternal mortality ratio. This
      paper outlines a number of complementary interventions used by the Nepal Safer
      Motherhood Project to address the negative attitudes prevalent among service
      providers, which is a contributing factor to the under-utilization of the health
      care services. The perspectives of the community and the service providers are
      presented, with a discussion of the importance of effective communication, the
      establishment of positive relationships and a demonstration of the critical role
      of local ownership and involvement in bringing about a positive change.

PMID- 18820179
TI  - A common RET variant is associated with reduced newborn kidney size and function.
AB  - Congenital nephron number varies five-fold among normal humans, and individuals
      at the lower end of this range may have an increased lifetime risk for essential
      hypertension or renal insufficiency; however, the mechanisms that determine
      nephron number are unknown. This study tested the hypothesis that common
      hypomorphic variants of the RET gene, which encodes a tyrosine kinase receptor
      critical for renal branching morphogenesis, might account for subtle renal
      hypoplasia in some normal newborns. A common single-nucleotide polymorphism
      (rs1800860 G/A) was identified within an exonic splicing enhancer in exon 7. The
      adenosine variant at mRNA position 1476 reduced affinity for spliceosome
      proteins, enhanced the likelihood of aberrant mRNA splicing, and diminished the
      level of functional transcript in human cells. In vivo, normal white newborns
      with an rs1800860(1476A) allele had kidney volumes 10% smaller and cord blood
      cystatin C levels 9% higher than those with the rs1800860(1476G) allele. These
      findings suggest that the RET(1476A) allele, in combination with other common
      polymorphic developmental genes, may account for subtle renal hypoplasia in a
      significant proportion of the white population. Whether this gene variant affects
      clinical outcomes requires further study.

PMID- 18820182
TI  - Maternal morbidity during postpartum period in a village of north India: a
      prospective study.
AB  - This prospective community-based study was conducted in the village of Chhainsa,
      Haryana, India, in order to discover the incidence and types of postpartum
      morbidity and the factors associated with the morbidities. The subjects were
      followed up to 42 days of postpartum with a minimum of three visits; the first
      visit was within 14 days of delivery and subsequent visits were every 14 days. A
      first visit was made to 211 women and 174 (82.46%) completed the study. Seventy
      four percent reported at least one morbidity and there were 1.75 reported
      morbidities per woman per postpartum period. Common problems reported were:
      weakness, lower abdominal pain, perineal pain, abnormal vaginal discharge, high
      fever, breast problems, excessive vaginal bleeding, etc. There was greater
      morbidity among women of lower socioeconomic status, parity >4, birth interval
      >36 months, having a breech or caesarean delivery or a delivery assisted by
      relatives/neighbours. A significant positive association was found between age
      and non-maintenance of the 'five cleans' during delivery. Seventy-five percent of
      those who had reported morbidity had taken some action, but only 20% sought help
      from a qualified doctor and 14% from other health workers.

PMID- 18820181
TI  - Pattern of severe maternal morbidity in a tertiary hospital of Delhi, India: a
      pilot study.
AB  - Severe maternal morbidity also known as 'near miss' may be a good indicator of
      the quality and effectiveness of obstetric care, as it may identify priorities in
      maternal care more rapidly than mortality alone. The objective of the study was
      to observe the pattern of severe maternal morbidity and its associated factors in
      a tertiary care hospital in Delhi. All patients admitted to the obstetrics and
      gynaecology department who fulfilled the definition of severe maternal morbidity
      conditions were included. A proforma was used to record sociodemographic,
      obstetric, antenatal care treatment and outcome details. A total of 63 women were
      included for analysis. The incidence of severe maternal morbidity was 3.3/100
      deliveries. The mean age of the patients was 26.3 +/- 5 years. More than half
      (55.5%) were uneducated: almost one-third (32%) were from outside Delhi - the
      median distance travelled was 10 km. The majority were antenatal admissions
      (68.3%). The proportion of postdelivery or abortion cases were greater among
      women who came from outside Delhi. Only 38.1% were registered during the
      antenatal period. The diagnoses were: eclampsia/pre-eclampsia (35%); haemorrhage
      (35%); sepsis (13%); obstructed labour (9.5%) and other medical conditions (11%).
      Severe anaemia was observed in 22% of cases. Only 43.5% were normal vaginal
      deliveries and 54.5% were delivered by caesarean section or with the use of
      instruments; 61.3% were live births. Hysterectomy was performed in 14.8%: the
      proportion of hysterectomy was higher in obstructed labour. Severe maternal
      morbidity cases constitute a significant burden on health resources.

PMID- 18820183
TI  - Childhood cancer in Sudan: 1999-2007.
AB  - There is paucity of information on childhood cancer from Sudan with the last
      studies published more than 20 years ago. This study aims to provide a current
      picture of childhood cancer in Sudan. Data was obtained from the hospital
      registry for the period May 1999 to June 2007 on all paediatric patients
      presenting to the Institute of Nuclear Medicine and Oncology, University of
      Gezira, Wad Madani, Sudan. There were 322 children with cancer during this time
      period with a male:female ratio of 1.6:1. Lymphomas (111, 35%), leukaemia (83,
      26%) and Wilms' tumour (43, 13%) were the three most common groups of tumours.
      Thirty percent of all lymphomas were Burkitt's lymphoma; 3.4% of all childhood
      cancer cases were nasopharyngeal carcinomas.

PMID- 18820184
TI  - Conservative management of splenic injury in the tropics.
AB  - We undertook this study in order to determine whether the conservative management
      of splenic injuries is a safe practice in a low-volume tropical hospital. We
      evaluated 69 consecutive patients with splenic injury prospectively. The outcome
      measures were morbidity and mortality rates, overall hospital stay and blood
      transfusion requirements. Spleen preservation was achieved in 85% (59) of cases.
      Of the 16 patients who underwent splenic surgery, six had splenorraphy (38%). The
      overall mortality was 4.3% (3) and the deaths were not related to the
      conservative management. Our findings suggest that not only is the conservative
      management of splenic injuries safe, but also that the repair of an enlarged
      spleen (splenorrhaphy) is safe and feasible in tropical hospital settings. The
      findings in this study provide further evidence that the conservative management
      of splenic injury in a tropical hospital without computed tomography scan is a
      safe practice.

PMID- 18820185
TI  - Laparoscopic cholecystectomy in a small rural hospital in Kashmir Valley, India.
AB  - This study evaluates the feasibility of performing laparoscopic cholecystectomy
      in order to reduce the expenditure in a 28-bed sub-district hospital in Kashmir,
      India. We report on a prospective clinical trail involving patients with gall
      bladder disease reported to the hospital from June 2005 till May 2007.

PMID- 18820186
TI  - A structured training module using an inexpensive endotrainer for improving the
      performance of trainee surgeons.
AB  - Training in minimal access surgery has always been difficult in developing
      countries with limited resources, non availability of formal animal labs,
      inaffordability of conventional endotrainers and lack of trained endosurgeons to
      help the amateurs. It is always difficult to start a new procedure in such places
      where not only the patients but the orthodox surgical fraternity are reluctant to
      accept new ideas and newer trends in surgery. After thorough discussions with
      senior surgeons, the author (who was the only trained endosurgeon to begin with)
      developed a training policy to train the surgeons over a period of time through
      various exercises before allowing them to assist him in the actual surgeries. A
      homemade, inexpensive endotrainer was designed for these exercises. Audio-visual
      seminars were held in between the training sessions. This training module can be
      employed by other rural hospitals to improve the skills of surgeons who are new
      to the art of endosurgery.

PMID- 18820187
TI  - The characteristics and causes of pleural effusions in Kumasi Ghana - a
      prospective study.

PMID- 18820188
TI  - Fever of unknown origin in the elderly: nine years experience in China.
AB  - This is a retrospective study of older patients admitted to the First and Second
      Affiliated Hospitals of Wenzhou Medical College, China, with a diagnosis of fever
      of unknown origin. The study took place from January 1998 to December 2006 among
      102 patients who fulfilled the criteria. Infections were responsible for 50 cases
      (49.1%), followed by no diagnosis in 27 (26.5%), miscellaneous in nine (8.8%),
      neoplasms in eight (7.8%) and connective tissue disease in another eight (7.8%).
      Mycobacterium TB was the most frequent type of infection diagnosed.

PMID- 18820189
TI  - The rise and fall of epidemic Neisseria meningitidis from a tertiary care
      hospital in Delhi, January 2005-June 2007.
AB  - Meningococcal meningitis is endemic in India. There has been a sudden surge of
      cases of meningococcal meningitis in 2005 in Delhi. Present study was undertaken
      to find out changing trends in incidence of this disease from a tertiary care
      hospital in New Delhi over a period of two and half years. All samples from
      suspected cases of meningococcal meningitis were subjected to Gram staining,
      culture and latex agglutination test for detection of Neisseria meningitidis
      (N.meningitidis). Antimicrobial susceptibility of all isolates was performed
      using the disc diffusion test. 78.6%, 71.4% and 100% of the samples were positive
      for N.meningitidis by smear examination, culture and latex agglutination test
      respectively. Except for resistance to Penicillin and Erythromycin in 8.8% and
      5.9%, the isolates were sensitive to the commonly used antibiotics. Using simple,
      rapid and reliable methods for diagnosis, defining risk factors and continuing
      surveillance remain important public health goals for the control of
      meningococcal disease.

PMID- 18820190
TI  - Frequency and determinants of the metabolic syndrome in apparently healthy adult
      Nigerians.
AB  - Non-communicable disease conditions such as the metabolic syndrome further strain
      the already insufficient health resources in Africa, where communicable diseases
      such as malaria and HIV/AIDS are still causing significant morbidity and
      mortality. We studied the frequency and determinants of the syndrome in
      apparently healthy Nigerian volunteers in order to provide a basis for the
      establishment of a prevention programme.

PMID- 18820191
TI  - Pigs are the most important animal reservoir for Tunga penetrans (jigger flea) in
      rural Nigeria.
AB  - We examined the domestic animals and rodents in a community in rural Nigeria. Of
      the 133 animals examined, 29 (21.8%) were infested, the highest prevalence of
      infestation and highest parasite load was found in the pigs (prevalence 54.8%,
      median = nine embedded parasites), followed by dogs (45.5%; median = 4), Rattus
      rattus (29.4%; median = 2) and Mus minutoides (15.4%; median = 1.5). Of all the
      tungiasis lesions identified 83% were found in pigs. Our data confirm that
      tungiasis is a zoonotic disease, and that pigs are its most important animal
      reservoir in this endemic community.

PMID- 18820192
TI  - The mental health consequences of intimate partner violence against women in
      Agaro Town, southwest Ethiopia.
AB  - There are very few population-based studies on the mental health consequences of
      intimate partner violence (IPV) from Ethiopia. This study was conducted among 510
      'ever partnered' women in Agaro Town in February 2007. Mental distress and
      depression were measured using self-reporting questionnaires and Kessler's
      Scales. All types of IPV (physical, sexual and emotional abuses) were
      significantly associated with mental distress and depression. Women who suffered
      from physical, sexual and emotional abuses were more likely to have mental
      distress. We recommend using information education communications to educate the
      community and thereby preventing IPV and the mental health consequences.

PMID- 18820193
TI  - Risk perception and water purification practices for water-borne parasitic
      infections in remote Nepal.
AB  - This study assesses water-borne infection risk perception and water boiling
      habits in a remote Sankhuwasava region of Nepal using a brief interview-style
      questionnaire. All subjects were aware of the risks associated with drinking
      unpurified water, but a majority (65%) reported they did not boil water
      regularly, and almost 60% of villagers interviewed had history of infection
      despite their boiling practices. In contrast to reports from other communities in
      Nepal, risk awareness was sufficient in this region. Water boiling alone did not
      confer protection. Future efforts should target sanitation, screening, and other
      sources of contamination.

PMID- 18820194
TI  - Incidence of skeletal deformities in endemic fluorosis.
AB  - An investigation was undertaken in three endemic fluorotic areas of Punjab State,
      India, to assess the prevalence of skeletal deformities. The concentration of
      fluoride in drinking water varies from 2.3 to 22.5 mg/L. The patients affected
      with skeletal fluorosis revealed joint pain in both upper and lower limbs,
      numbing and tingling of the extremities, back pains and knock-knees. Prevalence
      of skeletal fluorosis was found to be 29% of grade-I, 51% of grade-II and 20% of
      grade-III and was higher in males (63%) compared with females (37%).

PMID- 18820195
TI  - Epidemiology of nosocomial infections in medicine intensive care unit at a
      tertiary care hospital in northern India.
AB  - This prospective observational study describes the rates of nosocomial infections
      (NI), the sites of infection, the pathogens involved, their antibiogram and the
      risk factors at a tertiary care hospital in northern India. In 62 of the 182
      enrolled patients 95 episodes of NI were recorded (incidence rate 28.6/1000
      person days): pneumonia (77%); urinary tract infection (24%) and blood stream
      infection (24%). All isolates of Acinetobacter, Pseudomonas and Klebsiella and
      83.3% of Escherichia coli were resistant to the third generation cephalosporins.
      An increased duration of the time spent in intensive care units and days of
      intervention were associated with incident NI.

PMID- 18820196
TI  - Does breast feeding provide protection against acute appendicitis? A case-control
      study.
AB  - Breast feeding stimulates a more tolerant lymphoid tissue at the base of the
      appendix and this could provide protection against acute appendicitis. Two
      studies reported that children and adolescents with appendicitis were less likely
      to have been breast fed. In a case-control study of 200 children with
      histologically confirmed acute appendicitis matched by 200 siblings with the same
      sex and difference age - up to three-year-old - we found breast feeding in at
      least the first two months of life and for more than four months provides
      protection against acute appendicitis. These findings suggesting that breast
      feeding may possibly give protection against the development of appendicitis.

PMID- 18820197
TI  - High-risk behaviours and associated factors among HIV-positive individuals in
      clinical care in southwest Ethiopia.
AB  - A hospital-based cross-sectional survey was conducted among 705 HIV-positive
      individuals. The result showed that 24% of the participants reported unprotected
      intercourse in their most recent sexual episode. Nine percent of these events
      were with partners perceived to be HIV-negative and 39% with those of unknown HIV
      status. Protected sex at recent episode was independently associated with knowing
      a partner's HIV status, disclosing HIV status to a partner, receipt of
      antiretroviral treatment and perceiving HIV as less stigmatizing. This highlights
      the need for interventions among HIV-positive individuals that will assist them
      in attaining and maintaining safer sex practices.

PMID- 18820198
TI  - Osteomyelitis of the ribs: a strategy for prompt diagnosis and effective
      management.
AB  - Seven patients were treated for osteomyelitis rib (OR). Discharging sinuses and
      painful swellings were the presenting symptoms. An initial chest X-ray was
      unremarkable in all patients. Fine needle aspiration cytology and microscopy of
      pus did not reveal acid-fast bacillus in any patient. Computerized tomography
      (CT) of thorax was consistent with the diagnosis of OR in five patients. The
      patients underwent a subperiosteal excision of the affected part of the ribs or
      an excision biopsy of the unhealthy granulation tissue. Histopathological
      diagnosis was consistent with the diagnosis of tuberculosis (TB) OR in six
      patients. The patients received anti-TB drugs or appropriate antibiotics
      following surgery. All responded to treatment except one with a non-TB OR, who
      required further excision of the unhealthy rib ends. Inclusion of a CT of the
      thorax and an excision biopsy in the diagnostic process facilitates prompt
      diagnosis and effective management of OR.

PMID- 18820199
TI  - A study of clinico-haematological profiles of pancytopenia in children.
AB  - We report on the clinico-haematological profile of pancytopenia in children from
      the Departments of Pediatrics and Pathology, Institute of Medical Sciences,
      Banaras Hindu University, India, over a period of 30 months. Pancytopenia was
      defined as: haemoglobin <10 g/dL, absolute neutrophil count 1.5 x 10(9)/L and
      platelet count <100 x 10(9)/L. A detailed history, clinical examination and
      haematological parameters were recorded. Bone marrow aspiration and trephine
      biopsy were carried out in all cases. One hundred and five cases aged 1.5-18
      years, with a mean age of 8.6 years, were included in the study. Aplastic anaemia
      was the most common cause of pancytopenia (43%) followed by acute leukaemia
      (25%). Infections were the third most common cause of pancytopenia of which kala
      azar was the most common. Megaloblastic anaemia was seen in 6.7%.

PMID- 18820200
TI  - Clinical patterns and major causes of infertility among Sudanese couples.
AB  - An understanding of the medical causes of infertility is crucial in order to
      reduce incidences of Infertility and for improving the clinical management of
      infertility. Although there were much data on infertility in other African
      countries, no data exist on infertility in Sudan. Seven hundred and ten Sudanese
      couples were investigated for the infertility in Khartoum Fertility Center,
      Sudan: 443 (62.4%) had primary infertility and 267 (37.6%) had secondary
      infertility. The mean (standard deviation) duration of the infertility was 5.2
      (4.3) years. A positive male factor alone was found in 257 (36.2%) couples and a
      female factor in 350 (49.3%) couples: eleven (1.5%) couples had a combination of
      male and female factors: and the cause of infertility was unexplained in 92
      (13.0%) couples. Oligozoospermia and asthenozoospermia were factors responsible
      for 16.8% and 17.5% of male infertility, respectively. Failure of ovulation
      (60.3%) was the most common cause of female infertility. The study revealed a
      high proportion of secondary infertility and a greater contribution of the female
      factors to infertility.

PMID- 18820201
TI  - Fine needle aspiration cytology in the investigation of breast lumps at the
      University Teaching Hospital in Lusaka, Zambia.
AB  - The study was undertaken to determine the value of fine needle aspiration
      cytology (FNAC) in the investigation of breast lumps at the University Teaching
      Hospital (UTH) in Lusaka, Zambia. This technique, which has been shown to be
      cheap, simple and accurate has not been in common use at this institution. FNAC
      and open biopsy (OB) were performed on 56 patients who presented with a breast
      lump and the results compared, in order to determine the accuracy of FNAC. FNAC
      was found to have a sensitivity of 72% and specificity of 100%. This level of
      accuracy compares favourably with the quality assurance criteria set for breast
      FNAC by the Royal College of Pathologists in the British National Health Service
      (NHS).

PMID- 18820202
TI  - The incidence of urinary tract infections in febrile children during a two-year
      period in Tehran, Iran.
AB  - Of 433 febrile children examined in the paediatric clinics of two university
      hospitals in Tehran, Iran, 39 (9%) children (27 girls and 12 boys) were diagnosed
      as having urinary tract infection in which Escherichia coli was the most
      frequently detected pathogen (84.6%). According to the voiding cystourethrogram,
      nine (75%) boys and 17 (63%) girls had urinary tract abnormalities. This result
      is slightly higher than seen in other reports from developing countries.

PMID- 18820203
TI  - Risk of hepatitis B virus in the slaughter house.
AB  - The study involved 180 Nigerian butchers and 180 traders (controls) selected by
      multistage stratified sampling who had their sera assayed for HBsAg (hepatitis B
      surface antigen) by enzyme-linked immunosorbent assay method. The butchers and
      the controls had an HBsAg sero-prevalence rate of 9.4% and 3.3%, respectively.
      Various risky practices were more common among the butchers but their hepatitis B
      antigenaemia was not related to the duration of their occupational exposure. The
      study shows that the butchers constitute a high risk occupation for hepatitis B
      viral infection.

PMID- 18820204
TI  - Concomitant TB and cryptococcosis in HIV-infected patients.
AB  - Four cases of concomitant tuberculosis and cryptococcosis infection in HIV
      positive patients are described. As the HIV pandemic progresses and the
      proportion of patients with end-stage disease increases, a high suspicion of
      incidence and unusual forms of infections must always be kept in mind.

PMID- 18820205
TI  - Crimean Congo hemorrhagic fever and diffuse alveolar haemorrhage.
AB  - Although the pathology of Crimean Congo haemorrhagic fever (CCHF) is mainly
      related to a haemorrhagic process with secondary cytokine storm, there have been
      no published reports of this fatal disease being a cause of diffuse alveolar
      haemorrhage (DAH). There are many aetiological factors emphasizing the direct
      role of endothelial injury on DAH. We present the case of a young adult Turkish
      man with diffuse bilateral alveolar haemorrhage without an episode of gross
      haemoptysis caused by the CCHF virus. Successful clinical results and a rapid
      clinical and radiological clearance were obtained within few days after starting
      daily oral ribavirin treatment. This fatal infection should be considered to
      exist in any patient presenting with DAH, and should rapidly be treated with
      ribavirin. Another very important factor which should always be borne in mind is
      the contagious character of the CCHF virus. It is one of the most dangerous
      microorganisms transmitted from person to person. Even the bronchoscopes
      contaminated with patient blood carry a high risk for nosocomial spread to
      medical staff and other patients.

PMID- 18820206
TI  - Pyomyositis mimicking leptospirosis: two cases in a Brazilian tertiary care
      hospital in a non-tropical area.
AB  - Pyomyositis is a subacute, deep suppurative bacterial infection of skeletal
      muscle not arising from contiguous infection. It is presumably haematogenous in
      origin, and characterized by muscle pain and swelling. We report on two patients
      who presented with pyomyositis in a tertiary care hospital in temperate region
      located in southern Brazil with a clinical presentation, which was initially
      suggestive of leptospirosis. This report discusses the pathogenesis, clinical
      presentation, diagnosis and management of pyomyositis. Physicians living in non
      tropical areas should note that pyomyositis might occur in those areas, and its
      initial clinical presentation may be similar to leptospirosis.

PMID- 18820207
TI  - Primary amoebic meningoencephalitis: a new case from Venezuela.
AB  - Primary amoebic meningoencephalitis (PAM) is not often seen. To date, less than
      300 cases have been communicated to the medical literature since the disease was
      first discovered in 1965. Six of these reports originated in Venezuela. The
      authors describe a new spontaneous case of PAM in a 33-year-old previously
      healthy Western-Venezuelan man.

PMID- 18820208
TI  - Childhood epilepsy and school absence.
AB  - Epilepsy is one of the most common diseases encountered among school children.
      Its effect on school attendance and academic performance is a major cause of
      concern to both parents and clinicians. In this communication, the absence rate
      and academic performance of 50 school children with epilepsy attending normal
      schools was compared with that of their age- and sex-matched classmates using the
      class attendance register and overall score of the 2001/2002 academic year. The
      mean and standard deviation of the number of days an epileptic child was absent
      in the 2001/2002 session was 15.3 + 13.8 days while that of the controls was 9.4
      + 9.6 days (x2 = 3.4,df = 49, p < 0.001). There was no significant relationship
      between the rate of absenteeism and overall score among both epileptic children
      (x2 = 6.34, df = 2, p = 0.18) and the controls (x2 = 1.43, df = 2, p = 0.49).
      School absenteeism was therefore more common among epileptic children, though
      there was no observed negative effect of this increased absence on academic
      performance.

PMID- 18820209
TI  - Unforeseen difficulties faced by a hospital in dealing with mass disaster
      victims.
AB  - Every major mass disaster challenges the health care services, especially in the
      third world. These challenges include the expected situations mainly pertaining
      to the overload of patients and the stretching of hospital facilities. We report
      our experiences about several unforseen challenges faced by our hospital in the
      2005 earthquake that struck the Kashmir region.

PMID- 18820210
TI  - The "perfect storm" for type 1 diabetes: the complex interplay between intestinal
      microbiota, gut permeability, and mucosal immunity.
AB  - It is often stated that type 1 diabetes results from a complex interplay between
      varying degrees of genetic susceptibility and environmental factors. While
      agreeing with this principal, our desire is that this Perspectives article will
      highlight another complex interplay potentially associated with this disease
      involving facets related to the gut, one where individual factors that, upon
      their interaction with each another, form a "perfect storm" critical to the
      development of type 1 diabetes. This trio of factors includes an aberrant
      intestinal microbiota, a "leaky" intestinal mucosal barrier, and altered
      intestinal immune responsiveness. Studies examining the microecology of the
      gastrointestinal tract have identified specific microorganisms whose presence
      appears related (either quantitatively or qualitatively) to disease; in type 1
      diabetes, a role for microflora in the pathogenesis of disease has recently been
      suggested. Increased intestinal permeability has also been observed in animal
      models of type 1 diabetes as well as in humans with or at increased-risk for the
      disease. Finally, an altered mucosal immune system has been associated with the
      disease and is likely a major contributor to the failure to form tolerance,
      resulting in the autoimmunity that underlies type 1 diabetes. Herein, we discuss
      the complex interplay between these factors and raise testable hypotheses that
      form a fertile area for future investigations as to the role of the gut in the
      pathogenesis and prevention of type 1 diabetes.

PMID- 18820211
TI  - Mary, Mary, quite contrary, how do your beta-cells fail?

PMID- 18820212
TI  - Vitamin D and type 2 diabetes: are we ready for a prevention trial?

PMID- 18820213
TI  - Role of MicroRNA in pancreatic beta-cells: where more is less.

PMID- 18820215
TI  - Pancreas histology and a longitudinal study of insulin secretion in a Japanese
      patient with latent autoimmune diabetes in adults.

PMID- 18820214
TI  - Hepatocyte growth factor enhances engraftment and function of nonhuman primate
      islets.
AB  - OBJECTIVE: Adenoviral delivery of hepatocyte growth factor (HGF) to rodent islets
      improves islet graft survival and function, markedly reducing the number of
      islets required to achieve glucose control. Here, we asked whether these prior
      observations in rodent models extend to nonhuman primate (NHP) islets. RESEARCH
      DESIGN AND METHODS: NHP islets were transduced with murine (Ad.mHGF) or human
      (Ad.hHGF) adenoviral HGF (Ad.HGF) at low multiplicity of infection and studied in
      vitro. To study the function of Ad.HGF-transduced NHP islets in vivo, a renal
      subcapsular marginal mass islet transplant model was developed in streptozotocin
      induced diabetic NOD-SCID mice. RESULTS: Baseline glucose values were 454.7 +/-
      11.3 mg/dl (n = 7). Transplant of 500 NHP islet equivalents (IE) had only a
      marginal effect on blood glucose (369.1 +/- 9.7 mg/dl, n = 5). In striking
      contrast, 500 NHP IE transduced with Ad.mHGF promptly and continuously corrected
      blood glucose (142.0 +/- 6.2 mg/dl, n = 7) for the 6-week duration of the
      experiment. Unilateral nephrectomy resulted in an immediate return of glucose to
      baseline diabetic levels. Interestingly, adenoviral DNA, as well as mouse HGF
      (mHGF) mRNA derived from the adenovirus, were present for 42 days
      posttransplantation. Surprisingly, transplant of 500 IE with Ad.hHGF, as compared
      with Ad.mHGF, resulted in only marginal correction of blood glucose, suggesting
      that human HGF is less efficient than mHGF in this system. CONCLUSIONS: These
      studies demonstrate that mHGF markedly improves islet transplant outcomes in the
      highest preclinical species examined to date. HGF has promise as an agent that
      can improve islet mass and function in transplant models and likely in other
      models of types 1 and 2 diabetes.

PMID- 18820216
TI  - Bent needles: another problem in glycemic control.

PMID- 18820217
TI  - Predictive value of postoperative glycosuria after partial elective
      pancreatectomy in focal congenital hyperinsulinism.

PMID- 18820218
TI  - Elevated plasma plasminogen activator inhibitor-1 in CD36 deficiency.

PMID- 18820219
TI  - Self-monitoring of blood glucose, cutaneous finger injury, and sensory loss in
      diabetic patients.

PMID- 18820220
TI  - Prediction of mortality using measures of cardiac autonomic dysfunction in the
      diabetic and nondiabetic population: the MONICA/KORA Augsburg Cohort Study:
      response to Ziegler et al.

PMID- 18820222
TI  - Comparison of negative pressure wound therapy using vacuum-assisted closure with
      advanced moist wound therapy in the treatment of diabetic foot ulcers: a
      multicenter randomized controlled trial: response to Blume et al.

PMID- 18820224
TI  - Prognostic value of the insertion/deletion polymorphism of the ACE gene in type 2
      diabetic subjects: results from the Non-Insulin-Dependent Diabetes, Hypertension,
      Microalbuminuria or Proteinuria, Cardiovascular events, and Ramipril (DIABHYCAR),
      Diabete de type 2, Nephropathie et Genetique (DIAB2NEPHROGENE), and Survie,
      Diabete de type 2 et Genetique (SURDIAGENE) studies: response to Hadjadj et al.

PMID- 18820226
TI  - Comparison of the numerical and clinical accuracy of four continuous glucose
      monitors: response to Kovatchev et al.

PMID- 18820228
TI  - Cross-sectional and prospective study of lung function in adults with type 2
      diabetes: the Atherosclerosis Risk in Communities (ARIC) study: response to Yeh
      et al.

PMID- 18820229
TI  - American College Of Endocrinology Pre-Diabetes Consensus Conference: part one.

PMID- 18820230
TI  - No need for the needle (at first).

PMID- 18820231
TI  - Glycemic control and hypoglycemia: is the loser the winner?

PMID- 18820232
TI  - Spatial diffusivity and availability of intracellular calmodulin.
AB  - Calmodulin (CaM) is the major pathway that transduces intracellular Ca2+
      increases to the activation of a wide variety of downstream signaling enzymes.
      CaM and its target proteins form an integrated signaling network believed to be
      tuned spatially and temporally to control CaM's ability to appropriately pass
      signaling events downstream. Here, we report the spatial diffusivity and
      availability of CaM labeled with enhanced green fluorescent protein (eGFP)-CaM,
      at basal and elevated Ca2+,quantified by the novel fluorescent techniques of
      raster image scanning spectroscopy and number and brightness analysis. Our
      results show that in basal Ca2+ conditions cytoplasmic eGFP-CaM diffuses at a
      rate of 10 microm(2)/s, twofold slower than the noninteracting tracer, eGFP,
      indicating that a significant fraction of CaM is diffusing bound to other
      partners. The diffusion rate of eGFP-CaM is reduced to 7 microm(2)/s when a large
      (646 kDa) target protein Ca2+/CaM-dependent protein kinase II is coexpressed in
      the cells. In addition, the presence of Ca2+/calmodulin-dependent protein kinase
      II, which can bind up to 12 CaM molecules per holoenzyme, increases the
      stoichiometry of binding to an average of 3 CaMs per diffusive molecule.
      Elevating intracellular Ca2+ did not have a major impact on the diffusion of CaM
      complexes. These results present us with a model whereby CaM is spatially
      modulated by target proteins and support the hypothesis that CaM availability is
      a limiting factor in the network of CaM-signaling enzymes.

PMID- 18820233
TI  - Pore formation induced by an antimicrobial peptide: electrostatic effects.
AB  - We investigate the mode of action of Cateslytin, an antimicrobial peptide, on
      zwitterionic biomembranes by performing numerical simulations and
      electrophysiological measurements on membrane vesicles. Using this natural beta
      sheet antimicrobial peptide secreted during stress as a model we show that a
      single peptide is able to form a stable membrane pore of 1 nm diameter of 0.25 nS
      conductance found both from calculation and electrical measurements. The
      resulting structure does not resemble the barrel-stave or carpet models earlier
      predicted, but is very close to that found in the simulation of alpha-helical
      peptides. Based on the simulation of a mutated peptide and the effects of small
      external electric fields, we conclude that electrostatic forces play a crucial
      role in the process of pore formation.

PMID- 18820234
TI  - Spectral monitoring of surfactant clearance during alveolar epithelial type II
      cell differentiation.
AB  - In this study, we report on the noninvasive identification of spectral markers of
      alveolar type II (ATII) cell differentiation in vitro using Raman
      microspectroscopy. ATII cells are progenitor cells for alveolar type I (ATI)
      cells in vivo, and spontaneously differentiate toward an ATI-like phenotype in
      culture. We analyzed undifferentiated and differentiated primary human ATII
      cells, and correlated Raman spectral changes to cellular changes in morphology
      and marker protein synthesis (surfactant protein C, alkaline phosphatase,
      caveolin-1). Undifferentiated ATII cells demonstrated spectra with strong
      phospholipid vibrations, arising from alveolar surfactant stored within
      cytoplasmic lamellar bodies (Lbs). Differentiated ATI-like cells yielded spectra
      with significantly less lipid content. Factor analysis revealed a phospholipid
      dominated spectral component as the main discriminator between the ATII and ATI
      like phenotypes. Spectral modeling of the data revealed a significant decrease in
      the spectral contribution of cellular lipids-specifically phosphatidyl choline,
      the main constituent of surfactant, as ATII cells differentiate. These
      observations were consistent with the clearance of surfactant from Lbs as ATII
      cells differentiate, and were further supported by cytochemical staining for Lbs.
      These results demonstrate the first spectral characterization of primary human
      ATII cells, and provide insight into the biochemical properties of alveolar
      surfactant in its unperturbed cellular environment.

PMID- 18820235
TI  - Ensemble modeling of metabolic networks.
AB  - Complete modeling of metabolic networks is desirable, but it is difficult to
      accomplish because of the lack of kinetics. As a step toward this goal, we have
      developed an approach to build an ensemble of dynamic models that reach the same
      steady state. The models in the ensemble are based on the same mechanistic
      framework at the elementary reaction level, including known regulations, and span
      the space of all kinetics allowable by thermodynamics. This ensemble allows for
      the examination of possible phenotypes of the network upon perturbations, such as
      changes in enzyme expression levels. The size of the ensemble is reduced by
      acquiring data for such perturbation phenotypes. If the mechanistic framework is
      approximately accurate, the ensemble converges to a smaller set of models and
      becomes more predictive. This approach bypasses the need for detailed
      characterization of kinetic parameters and arrives at a set of models that
      describes relevant phenotypes upon enzyme perturbations.

PMID- 18820236
TI  - Minimal folding pathways for coarse-grained biopolymer fragments.
AB  - The minimal folding pathway or trajectory for a biopolymer can be defined as the
      transformation that minimizes the total distance traveled between a folded and an
      unfolded structure. This involves generalizing the usual Euclidean distance from
      points to one-dimensional objects such as a polymer. We apply this distance here
      to find minimal folding pathways for several candidate protein fragments,
      including the helix, the beta-hairpin, and a nonplanar structure where chain
      noncrossing is important. Comparing the distances traveled with root mean-squared
      distance and mean root-squared distance, we show that chain noncrossing can have
      large effects on the kinetic proximity of apparently similar conformations.
      Structures that are aligned to the beta-hairpin by minimizing mean root-squared
      distance, a quantity that closely approximates the true distance for long chains,
      show globally different orientation than structures aligned by minimizing root
      mean-squared distance.

PMID- 18820237
TI  - Slow motions in chicken villin headpiece subdomain probed by cross-correlated NMR
      relaxation of amide NH bonds in successive residues.
AB  - The villin headpiece subdomain (HP36) is a widely used system for protein-folding
      studies. Nuclear magnetic resonance cross-correlated relaxation rates arising
      from correlated fluctuations of two N-H(N) dipole-dipole interactions involving
      successive residues were measured at two temperatures at which HP36 is at least
      99% folded. The experiment revealed the presence of motions slower than overall
      tumbling of the molecule. Based on the theoretical analysis of the spectral
      densities we show that the structural and dynamic contributions to the
      experimental cross-correlated relaxation rate can be separated under certain
      conditions. As a result, dynamic cross-correlated order parameters describing
      slow microsecond-to-millisecond motions of N-H bonds in neighboring residues can
      be introduced for any extent of correlations in the fluctuations of the two bond
      vectors. These dynamic cross-correlated order parameters have been extracted for
      HP36. The comparison of their values at two different temperatures indicates that
      when the temperature is raised, slow motions increase in amplitude. The increased
      amplitude of these fluctuations may reflect the presence of processes directly
      preceding the unfolding of the protein.

PMID- 18820238
TI  - Mechanical properties of actin stress fibers in living cells.
AB  - Actin stress fibers (SFs) play an important role in many cellular functions,
      including morphological stability, adhesion, and motility. Because of their
      central role in force transmission, it is important to characterize the
      mechanical properties of SFs. However, most of the existing studies focus on
      properties of whole cells or of actin filaments isolated outside cells. In this
      study, we explored the mechanical properties of individual SFs in living
      endothelial cells by nanoindentation using an atomic force microscope. Our
      results demonstrate the pivotal role of SF actomyosin contractile level on
      mechanical properties. In the same SF, decreasing contractile level with 10
      microM blebbistatin decreased stiffness, whereas increasing contractile level
      with 2 nM calyculin A increased stiffness. Incrementally stretching and indenting
      SFs made it possible to determine stiffness as a function of strain level and
      demonstrated that SFs have nearly linear stress-stain properties in the baseline
      state but nonlinear properties at a lower contractile level. The stiffnesses of
      peripheral and central portions of the same SF, which were nearly the same in the
      baseline state, became markedly different after contractile level was increased
      with calyculin A. Because these results pertain to effects of interventions in
      the same SF in a living cell, they provide important new understanding about cell
      mechanics.

PMID- 18820239
TI  - Incorporating dipolar solvents with variable density in Poisson-Boltzmann
      electrostatics.
AB  - We describe a new way to calculate the electrostatic properties of macromolecules
      that goes beyond the classical Poisson-Boltzmann treatment with only a small
      extra CPU cost. The solvent region is no longer modeled as a homogeneous
      dielectric media but rather as an assembly of self-orienting interacting dipoles
      of variable density. The method effectively unifies both the Poisson-centric view
      and the Langevin Dipole model. The model results in a variable dielectric
      constant epsilon(r) in the solvent region and also in a variable solvent density
      rho(r) that depends on the nature of the closest exposed solute atoms. The model
      was calibrated using small molecules and ions solvation data with only two
      adjustable parameters, namely the size and dipolar moment of the solvent.
      Hydrophobicity scales derived from the solvent density profiles agree very well
      with independently derived hydrophobicity scales, both at the atomic or residue
      level. Dimerization interfaces in homodimeric proteins or lipid-binding regions
      in membrane proteins clearly appear as poorly solvated patches on the solute
      accessible surface. Comparison of the thermally averaged solvent density of this
      model with the one derived from molecular dynamics simulations shows qualitative
      agreement on a coarse-grained level. Because this calculation is much more rapid
      than that from molecular dynamics, applications of a density-profile-based
      solvation energy to the identification of the true structure among a set of
      decoys become computationally feasible. Various possible improvements of the
      model are discussed, as well as extensions of the formalism to treat mixtures of
      dipolar solvents of different sizes.

PMID- 18820240
TI  - Conformation and free energy analyses of the complex of calcium-bound calmodulin
      and the Fas death domain.
AB  - Previous studies have demonstrated a calcium-dependent interaction of calmodulin
      (CaM) and Fas that is regulated during Fas-induced apoptosis in several cell
      lines, including cholangiocarcinoma, Jurkat cells, and osteoclasts. The binding
      of CaM and Fas has been identified on residues 231-254 of Fas; the V254N point
      mutation decreases the CaM/Fas binding, and the C-terminal deletion mutation
      increases the CaM/Fas binding. Recent studies have shown that CaM is recruited
      into the Fas-mediated death-inducing signaling complex (DISC) in a calcium
      dependent manner. However, the molecular mechanisms whereby Fas mutations and
      CaM/Fas binding might regulate Fas-mediated DISC formation are unknown. In this
      study we investigated the binding thermodynamics and conformation of the CaM/Fas
      complexes with combined explicit solvent molecular-dynamics simulations and
      implicit solvent binding free-energy calculations. The binding free-energy
      analysis demonstrated that the Fas V254N point mutation reduced its binding
      affinity with CaM. In contrast, the Fas mutant with the deletion of the 15 amino
      acid at the C-terminus increased its binding to CaM. These observations are
      consistent with previous findings from biochemical studies. Conformational
      analyses further showed that the Fas V254N mutation resulted in an unstable
      conformation, whereas the C-terminal deletion mutation stabilized the Fas
      conformation, and both mutations resulted in changes of the degree of correlation
      between the motions of the residues in Fas. Analysis of the CaM/Fas complex
      revealed that CaM/Fas binding stabilized the conformation of both CaM and Fas and
      changed the degree of correlated motion of the residues of CaM and Fas. The
      results presented here provide structural evidence for the roles of Fas mutations
      and CaM/Fas binding in Fas-induced DISC formation. Understanding the molecular
      mechanisms of CaM/Fas binding in Fas-mediated DISC formation should provide
      important insights into the function of Fas mutations and CaM in regulating Fas
      mediated apoptosis.

PMID- 18820241
TI  - Loss of small heterodimer partner expression in the liver protects against
      dyslipidemia.
AB  - Multiple studies suggest increased conversion of cholesterol to bile acids by
      cholesterol 7alpha-hydroxylase (CYP7A1) protects against dyslipidemia and
      atherosclerosis. CYP7A1 expression is repressed by the sequential activity of two
      nuclear hormone receptors, farnesoid X receptor (FXR) and small heterodimer
      partner (SHP). Here we demonstrate 129 strain SHP(-/-) mice are protected against
      hypercholesterolemia resulting from either a cholesterol/cholic acid (chol/CA)
      diet or from hypothyroidism. In a mixed 129-C57Bl/6 background, LDLR(-/-) and
      LDLR(-/-)SHP(-/-) mice had nearly identical elevations in hepatic cholesterol
      content and repression of cholesterol regulated genes when fed a Western diet.
      However, the LDLR(-/-)SHP(-/-) mice had greatly reduced elevations in serum VLDL
      and LDL cholesterol levels and triglyceride (TG) levels as compared with LDLR(-/
      ) mice. Additionally, the hepatic inflammation produced by the Western diet in
      the LDLR(-/-) mice was abolished in the LDLR(-/-)SHP(-/-) mice. CYP7A1 expression
      was induced 10-fold by the Western diet in the LDLR(-/-)SHP(-/-) mice but not in
      the LDLR(-/-) mice. Finally, hepatocyte-specific deletion of SHP expression was
      also protective against dyslipidemia induced by either a chol/CA diet or by
      hypothyroidism. While no antagonist ligands have yet been identified for SHP,
      these results suggest selective inhibition of hepatic SHP expression may provide
      protection against dyslipidemia.

PMID- 18820242
TI  - Novel noncoding antisense RNA transcribed from human anti-NOS2A locus is
      differentially regulated during neuronal differentiation of embryonic stem cells.
AB  - Here, we report on the discovery of a locus in the human genome, which evolved by
      gene duplication followed by an internal DNA inversion. This locus exhibits high
      sequence similarity to the gene for the inducible isoform of NOS protein (NOS2A)
      and is transcribed into a noncoding RNA containing a region of significant
      antisense homology with the NOS2A mRNA. We show that this antisense transcript
      (anti-NOS2A RNA) is expressed in different types of brain tumors, including
      meningiomas and glioblastomas. More importantly, we demonstrate that the
      expression profiles of the anti-NOS2A RNA and the NOS2A mRNA exhibit concurrent
      reciprocal changes in undifferentiated human embryonic stem cells (hESCs) and in
      hESCs induced to differentiate into neurogenic precursors such as neurospheres.
      As NOS2A has a role in neurogenesis, our results suggest that the anti-NOS2A RNA
      is involved in the regulation of neuronal differentiation of hESCs through the
      modulation of NOS2A gene expression.

PMID- 18820243
TI  - Monitoring circulating epithelial tumor cells (CETCs) during primary systemic
      chemotherapy including trastuzumab for early prediction of outcome in patients
      with Her2/neu-positive tumors.

PMID- 18820244
TI  - Is initially metastatic breast carcinoma different from recurrent metastatic
      breast carcinoma?

PMID- 18820245
TI  - Risk of recurrence during follow-up for optimally treated advanced epithelial
      ovarian cancer (EOC) with a low-level increase of serum CA-125 levels.
AB  - BACKGROUND: Our group evaluated the risk of recurrence for optimally treated
      advanced epithelial ovarian cancer (adEOC) in patients with a low-level rising
      serum CA-125 concentration within the normal range (0-35 kU/l). In addition, we
      tested the new proposed early CA-125 signal of progressive disease (EPD)
      criterion in the same study population. PATIENTS AND METHODS: Patients treated
      from 1998 to 2006 for adEOC were identified at our institution. Inclusion
      criteria were as follows: CA-125 at time of diagnosis (>35 kU/l); International
      Federation of Gynecology and Obstetrics stages III-IV treated with optimal
      primary treatment; and complete response (CR) to primary treatment with
      normalization of CA-125. RESULTS: Median progression-free survival and overall
      survival for the recurrence group (n = 60) were 17.7 and 38.2 months,
      respectively. The median follow-up time from CR to last contact was 40.2 months
      for patients in the nonrecurrence group (n = 36). An absolute increase in serum
      CA-125 levels of >or=5 kU/l compared with baseline CA-125 nadir values was
      significantly predictive of recurrence (odds ratio for recurrence = 402.98, P <
      0.0001). The progression date was predated by the EPD criterion in 77% of
      patients with known progressive disease (median, 58 days early) with a
      sensitivity of 90%, a positive predictive value of 96.4%, and a false-positive
      rate of 5.6%. CONCLUSIONS: Among patients with optimally treated adEOC in
      complete remission, a low-level increase in serum CA-125 concentration within the
      normal range is a strong independent predictive factor for disease recurrence. In
      this patient population, future prospective randomized trials should consider the
      evaluation of the EPD criterion.

PMID- 18820246
TI  - Using GEFs to deorphanize odorant receptors.

PMID- 18820247
TI  - Pre-incisional epidural magnesium provides pre-emptive and preventive analgesia
      in patients undergoing abdominal hysterectomy.
AB  - BACKGROUND: This prospective, randomized, double-blind study was designed to
      evaluate the preemptive and preventive analgesic efficacy of adding magnesium to
      a multimodal regimen of patient-controlled epidural analgesia (PCEA) in patients
      undergoing abdominal hysterectomy. METHODS: Ninety patients were randomly
      assigned to one of the three groups. Pre-magnesium patients received bolus of
      magnesium 50 mg epidurally before induction of anaesthesia followed by infusion
      of 10 mg h(-1) until end of surgery. Post-magnesium patients received epidural
      saline during the same time periods plus bolus epidural magnesium 50 mg at the
      end of surgery. Patients in the control group received epidural saline during all
      three periods. Patients in the magnesium groups received PCEA with fentanyl 1
      microg ml(-1), bupivacaine 0.08%, and magnesium 1 mg ml(-1) after operation.
      Patients in the control group received PCEA with fentanyl 1 microg ml(-1) and
      bupivacaine 0.08%. Data were recorded for three postoperative days. RESULTS:
      There were significantly lower pain scores on rest or movement in the pre
      magnesium group compared with the post-magnesium and control groups (P<0.05). The
      daily analgesic consumption in the pre-magnesium group was significantly less
      than the other two groups (P<0.05) and the dose consumed in the post-magnesium
      group was significantly smaller than the control group (P<0.05). The groups were
      similar with respect to haemodynamic and respiratory variables, sedation,
      pruritus, nausea, and vomiting. CONCLUSIONS: Continuous epidural magnesium
      started before anaesthesia provided preemptive, preventive analgesia, and an
      analgesic-sparing effect that improved postoperative analgesia without increasing
      the incidence of side-effects.

PMID- 18820248
TI  - Effect of prewarming on post-induction core temperature and the incidence of
      inadvertent perioperative hypothermia in patients undergoing general anaesthesia.
AB  - BACKGROUND: Inadvertent perioperative hypothermia (IPH) occurs in many patients
      because warming techniques are insufficient to counteract thermal redistribution
      resulting from the ablation of thermoregulatory vasoconstriction associated with
      anaesthesia. We tested the efficiency of a preoperative forced-air warming (FAW)
      device (Bair Paws) in preventing IPH. METHODS: Sixty-eight adult patients
      undergoing spinal surgery under general anaesthesia were randomized to receive
      either normal care or prewarming for 60 min, at 38 degrees C, using the Bair Paws
      system. All patients received routine FAW intraoperatively. RESULTS: Thirty-one
      patients were prewarmed and 37 patients were in the control group. There was a
      0.3 degrees C smaller decrease in mean core temperature in the prewarmed group at
      40, 60, and 80 min post-induction (P< or =0.05). Temperature was maintained above
      the hypothermic threshold of 36 degrees C in 21 (68%) patients in the prewarmed
      group, compared with 16 (43%) patients in the control group (P<0.05).
      CONCLUSIONS: Preoperative warming using the Bair Paws system results in smaller
      decreases in core temperature intraoperatively and less IPH in patients
      undergoing spinal surgery under general anaesthesia.

PMID- 18820249
TI  - SCN5A overlap syndromes: no end to disease complexity?

PMID- 18820250
TI  - Wide complex tachycardia in a healthy young man.
AB  - We describe a case of a young man referred with a broad complex tachycardia for
      evaluation and ablation. Electrophysiological study was performed and revealed a
      left lateral accessory pathway with antegrade decremental conduction causing
      antidromic reciprocating re-entrant tachycardia. Ablation was successfully
      performed. Left lateral accessory pathways with decremental conduction are rarely
      encountered.

PMID- 18820251
TI  - Bizarre case of migration of a retained epicardial pacing wire.
AB  - A 71-year-old woman, who had undergone mitral valve replacement procedure 2 years
      previously, presented with aortic and mitral prosthetic valve endocarditis.
      Preoperative examination demonstrated a wire-like structure coursing from the
      aortic bulb to the right carotid artery. The wire-like structure was removed
      during the mitral and aortic valve reoperation, and identified as an epicardial
      pacing wire, which was placed during the patients' first mitral valve operation.
      We suspect that the contaminated pacing wire migrated via the left atrium and
      left ventricle into the right carotid artery causing an infective endocarditis of
      the prosthetic mitral valve and the native aortic valve.

PMID- 18820252
TI  - An ancient evolutionary origin of genes associated with human genetic diseases.
AB  - Several thousand genes in the human genome have been linked to a heritable
      genetic disease. The majority of these appear to be nonessential genes (i.e., are
      not embryonically lethal when inactivated), and one could therefore speculate
      that they are late additions in the evolutionary lineage toward humans. Contrary
      to this expectation, we find that they are in fact significantly overrepresented
      among the genes that have emerged during the early evolution of the metazoa.
      Using a phylostratigraphic approach, we have studied the evolutionary emergence
      of such genes at 19 phylogenetic levels. The majority of disease genes was
      already present in the eukaryotic ancestor, and the second largest number has
      arisen around the time of evolution of multicellularity. Conversely, genes
      specific to the mammalian lineage are highly underrepresented. Hence, genes
      involved in genetic diseases are not simply a random subset of all genes in the
      genome but are biased toward ancient genes.

PMID- 18820253
TI  - Genome size reduction in the chicken has involved massive loss of ancestral
      protein-coding genes.
AB  - Both mean genomes size and the variance in genome size among species are smaller
      on average in birds (class Aves) than in the other tetrapod classes. In order to
      test whether loss of protein-coding genes has contributed to genome size
      reduction in birds, we compared the chicken genome and five mammalian genomes.
      Numbers of members (paralogs) were significantly lower in the chicken gene
      families than in the corresponding mammalian families. Phylogenetic analyses of
      chicken, mammal, and fish paralogs supported the hypothesis that chicken-specific
      loss of paralogs occurred much more frequently than mammal-specific gene
      duplications. Moreover, the phylogenetic analyses supported the hypothesis that a
      substantial majority of the paralogs lost in chicken originated from duplications
      prior to the most recent common ancestor of tetrapods and bony fishes. In
      addition to loss of paralogs, numerous gene families present in the mammalian
      genomes were missing in the chicken genome; over 1,000 of these families were
      found in bony fishes, implying presence of the family in the tetrapod ancestor.
      In the set of families with more members on average in the mammals than in the
      chicken, immune system function was associated with a greater degree of gene
      family size reduction in the chicken, consistent with other evidence that immune
      system gene families have become particularly compact in birds.

PMID- 18820254
TI  - The Apicomplexan whole-genome phylogeny: an analysis of incongruence among gene
      trees.
AB  - The protistan phylum Apicomplexa contains many important pathogens and is the
      subject of intense genome sequencing efforts. Based upon the genome sequences
      from seven apicomplexan species and a ciliate outgroup, we identified 268 single
      copy genes suitable for phylogenetic inference. Both concatenation and consensus
      approaches inferred the same species tree topology. This topology is consistent
      with most prior conceptions of apicomplexan evolution based upon ultrastructural
      and developmental characters, that is, the piroplasm genera Theileria and Babesia
      form the sister group to the Plasmodium species, the coccidian genera Eimeria and
      Toxoplasma are monophyletic and are the sister group to the Plasmodium species
      and piroplasm genera, and Cryptosporidium forms the sister group to the above
      mentioned with the ciliate Tetrahymena as the outgroup. The level of incongruence
      among gene trees appears to be high at first glance; only 19% of the genes
      support the species tree, and a total of 48 different gene-tree topologies are
      observed. Detailed investigations suggest that the low signal-to-noise ratio in
      many genes may be the main source of incongruence. The probability of being
      consistent with the species tree increases as a function of the minimum bootstrap
      support observed at tree nodes for a given gene tree. Moreover, gene sequences
      that generate high bootstrap support are robust to the changes in alignment
      parameters or phylogenetic method used. However, caution should be taken in that
      some genes can infer a "wrong" tree with strong support because of paralogy,
      model violations, or other causes. The importance of examining multiple, unlinked
      genes that possess a strong phylogenetic signal cannot be overstated.

PMID- 18820255
TI  - Evolution of soldier-specific venomous protease in social aphids.
AB  - In social aphids of the genus Tuberaphis a cysteine protease gene of the family
      cathepsin B exhibits soldier-specific expression and intestinal protease
      production. The product is orally excreted and injected by soldier nymphs into
      natural enemies, thereby exerting an insecticidal activity. In an attempt to gain
      insights into when and how the novel venomous protease for the altruistic caste
      has evolved, we investigated the soldier-specific type (S-type) and nonspecific
      type (N-type) cathepsin B genes from social and nonsocial aphids. All the social
      aphids examined, representing the genera Tuberaphis, Astegopteryx, and
      Cerataphis, possessed both the S-type and N-type genes. Phylogenetically distant
      nonsocial aphids also possessed cathepsin B genes allied to the S-type and the N
      type, indicating the evolutionary origin of these genes in the common ancestor of
      extant aphids. In Tuberaphis species the S-type genes exhibited significant
      soldier-specific expression and accelerated molecular evolution whereas the N
      type genes did not. In Astegopteryx and Cerataphis species, meanwhile, both the S
      type and N-type genes exhibited neither remarkable soldier-specific expression
      nor accelerated molecular evolution. These results suggest that the S-type gene
      acquired the soldier-specific expression and the venom function after divergence
      of the genus Tuberaphis. On the structural model of the S-type protease of
      Tuberaphis styraci the accelerated molecular evolution was associated with the
      molecular surface rather than the catalytic cleft, suggesting that the venom
      activity was probably acquired by relatively minor modifications on the molecular
      surface rather than by generation of a novel active site. In Cerataphis jamuritsu
      the S-type gene was, although containing a stop codon, structurally almost intact
      and still transcribed, suggesting recent pseudogenization of the gene copy and
      possible relevance to relaxed functional constraint in the highly multiplied
      protease gene family. On the basis of these results we suggest that the massive
      amplification in aphid cathepsin B genes might have predisposed the evolution of
      venomous protease in the social aphid lineage and argue that gene duplication,
      accelerated molecular evolution, and acquisition of novel gene function must have
      played considerable roles in the evolution of complex biological systems
      including insect sociality.

PMID- 18820256
TI  - Mapping of the hormone-sensitive lipase binding site on the adipocyte fatty acid
      binding protein (AFABP). Identification of the charge quartet on the AFABP/aP2
      helix-turn-helix domain.
AB  - The hormone-sensitive lipase (HSL) and adipocyte fatty acid-binding protein
      (AFABP/aP2) form a physical complex that affects basal and hormone-stimulated
      adipocyte fatty acid efflux. Previous work has established that AFABP/aP2-HSL
      complex formation requires that HSL be in its activated, phosphorylated form and
      AFABP/aP2 have a bound fatty acid. To identify the HSL binding site of AFABP/aP2
      a combination of alanine-scanning mutagenesis and fluorescence resonance energy
      transfer was used. Mutation of Asp17, Asp18, Lys21, or Arg30 (but not other amino
      acids in the helix-turn-helix region) to alanine inhibited interaction with HSL
      without affecting fatty acid binding. The cluster of residues on the helical
      domain of AFABP/aP2 form two ion pairs (Asp17-Arg30 and Asp18-Lys21) and
      identifies the region we have termed the charge quartet as the HSL interaction
      site. To demonstrate direct association, the non-interacting AFABP/aP2-D18K
      mutant was rescued by complementary mutation of HSL (K196E). The charge quartet
      is conserved on other FABPs that interact with HSL such as the heart and
      epithelial FABPs but not on non-interacting proteins from the liver or intestine
      and may be a general protein interaction domain utilized by fatty acid-binding
      proteins in regulatory control of lipid metabolism.

PMID- 18820257
TI  - TSG-6 transfers proteins between glycosaminoglycans via a Ser28-mediated covalent
      catalytic mechanism.
AB  - Studies of the interaction between Bikunin proteins, tumor necrosis factor
      stimulated gene-6 protein (TSG-6), and glycosaminoglycans have revealed a unique
      catalytic activity where TSG-6/heavy chain 2 transfer heavy chain subunits
      between glycosaminoglycan chains. The activity is mediated by TSG-6/heavy chain 2
      and involves a transient SDS stable interaction between TSG-6 and the heavy chain
      to be transferred. The focus of this study was to characterize the molecular
      structure of this cross-link to gain further insight into the catalytic
      mechanism. The result showed that the C-terminal Asp residue of the heavy chains
      forms an ester bond to Ser(28) beta-carbon of TSG-6 suggesting that this residue
      plays a role during catalysis.

PMID- 18820258
TI  - Challenging current paradigms related to cardiomyopathies. Are changes in the
      Ca2+ sensitivity of myofilaments containing cardiac troponin C mutations (G159D
      and L29Q) good predictors of the phenotypic outcomes?
AB  - Two novel mutations (G159D and L29Q) in cardiac troponin C (CTnC) associate their
      phenotypic outcomes with dilated (DCM) and hypertrophic cardiomyopathy (HCM),
      respectively. Current paradigms propose that sarcomeric mutations associated with
      DCM decrease the myofilament Ca2+ sensitivity, whereas those associated with HCM
      increase it. Therefore, we incorporated the mutant CTnCs into skinned cardiac
      muscle in order to determine if their effects on the Ca2+ sensitivities of
      tension and ATPase activity coincide with the current paradigms and phenotypic
      outcomes. The G159D-CTnC decreases the Ca2+ sensitivity of tension and ATPase
      activation and reduces the maximal ATPase activity when incorporated into
      regulated actomyosin filaments. Under the same conditions, the L29Q-CTnC has no
      effect. Surprisingly, changes in the apparent G159D-CTnC Ca2+ affinity measured
      by tension in fibers do not occur in the isolated CTnC, and large changes
      measured in the isolated L29Q-CTnC do not manifest in the fiber. These
      counterintuitive findings are justified through a transition in Ca2+ affinity
      occurring at the level of cardiac troponin and higher, implying that the true
      effects of these mutations become apparent as the hierarchical level of the
      myofilament increases. Therefore, the contractile apparatus, representing a large
      cooperative machine, can provide the potential for a change (G159D) or no change
      (L29Q) in the Ca2+ regulation of contraction. In accordance with the clinical
      outcomes and current paradigms, the desensitization of myofilaments from G159D
      CTnC is expected to weaken the contractile force of the myocardium, whereas the
      lack of myofilament changes from L29Q-CTnC may preserve diastolic and systolic
      function.

PMID- 18820259
TI  - Distinct roles of beta1 metal ion-dependent adhesion site (MIDAS), adjacent to
      MIDAS (ADMIDAS), and ligand-associated metal-binding site (LIMBS) cation-binding
      sites in ligand recognition by integrin alpha2beta1.
AB  - Integrin-ligand interactions are regulated in a complex manner by divalent
      cations, and previous studies have identified ligand-competent, stimulatory, and
      inhibitory cation-binding sites. In collagen-binding integrins, such as
      alpha2beta1, ligand recognition takes place exclusively at the alpha subunit I
      domain. However, activation of the alphaI domain depends on its interaction with
      a structurally similar domain in the beta subunit known as the I-like or betaI
      domain. The top face of the betaI domain contains three cation-binding sites: the
      metal-ion dependent adhesion site (MIDAS), the ADMIDAS (adjacent to MIDAS), and
      LIMBS (ligand-associated metal-binding site). The role of these sites in
      controlling ligand binding to the alphaI domain has yet to be elucidated.
      Mutation of the MIDAS or LIMBS completely blocked collagen binding to
      alpha2beta1; in contrast mutation of the ADMIDAS reduced ligand recognition but
      this effect could be overcome by the activating monoclonal antibody TS2/16.
      Hence, the MIDAS and LIMBS appear to be essential for the interaction between
      alphaI and betaI, whereas occupancy of the ADMIDAS has an allosteric effect on
      the conformation of betaI. An activating mutation in the alpha2 I domain
      partially restored ligand binding to the MIDAS and LIMBS mutants. Analysis of the
      effects of Ca(2+), Mg(2+), and Mn(2+) on ligand binding to these mutants showed
      that the MIDAS is a ligand-competent site through which Mn(2+) stimulates ligand
      binding, whereas the LIMBS is a stimulatory Ca(2+)-binding site, occupancy of
      which increases the affinity of Mg(2+) for the MIDAS.

PMID- 18820260
TI  - Response of plasma membrane H+-ATPase to heavy metal stress in Cucumis sativus
      roots.
AB  - The effect of heavy metals on the modification of plasma membrane H(+)-ATPase (EC
      3.6.3.14) activity in cucumber roots was studied. In plants stressed for 2 h with
      10 microM or 100 microM Cd, Cu or Ni the hydrolytic as well as the transporting
      activity of H(+)-ATPase in the plasma membranes of root cells was decreased.
      Transcript levels of Cucumis sativus plasma membrane H(+)-ATPase in roots treated
      with 10 microM Cd, Cu, or Ni as well as with 100 microM Cu or Ni were similar to
      the control, indicating that the action of metals did not involve the gene
      expression level. Only in roots exposed to 100 microM Cd was the level of plasma
      membrane H(+)-ATPase mRNA markedly decreased. The inhibition of the plasma
      membrane proton pump caused by 100 microM Cd, Cu and Ni was partially diminished
      in the presence of cantharidin, a specific inhibitor of protein phosphatases.
      Western blot analysis with the antibody against phosphothreonine confirmed that
      decreased activity of plasma membrane H(+)-ATPase under heavy metals resulted
      from dephosphorylation of the enzyme protein. Taken together, these data strongly
      indicated that alteration of the enzyme under heavy metal stresses was mainly due
      to the post-translational modification of its proteins in short-term experiments.

PMID- 18820261
TI  - Preventing childhood obesity: the sentinel site for obesity prevention in
      Victoria, Australia.
AB  - In spite of greater awareness of the need for action to reduce obesity, the
      evidence on sustainable community approaches to prevent childhood and adolescent
      obesity is surprisingly sparse. This paper describes the design and
      methodological components of the Sentinel Site for Obesity Prevention, a
      demonstration site in the Barwon-South West region of Victoria, Australia, that
      aims to build the programs, skills and evidence necessary to attenuate and
      eventually reverse the obesity epidemic in children and adolescents. The Sentinel
      Site for Obesity Prevention is based on a partnership between the region's
      university (Deakin University) and its health, education and local government
      agencies. The three basic foundations of the Sentinel Site are: multi-strategy,
      multi-setting interventions; building community capacity; and undertaking program
      evaluations and population monitoring. Three intervention projects have been
      supported that cover different age groups (preschool: 2-5 years, primary school:
      5-12 years, secondary school: 13-17 years), but that have many characteristics in
      common including: community participation and ownership of the project; an
      intervention duration of at least 3 years; and full evaluations with impact
      (behaviours) and outcome measures (anthropometry) compared with regionally
      representative comparison populations. We recommend the Sentinel Site approach to
      others for successfully building evidence for childhood obesity prevention and
      stimulating action on reducing the epidemic.

PMID- 18820262
TI  - Do we need multiple models of auditory verbal hallucinations? Examining the
      phenomenological fit of cognitive and neurological models.
AB  - The causes of auditory verbal hallucinations (AVHs) are still unclear. The
      evidence for 2 prominent cognitive models of AVHs, one based on inner speech, the
      other on intrusions from memory, is briefly reviewed. The fit of these models, as
      well as neurological models, to the phenomenology of AVHs is then critically
      examined. It is argued that only a minority of AVHs, such as those with content
      clearly relating to verbalizations experienced surrounding previous trauma, are
      consistent with cognitive AVHs-as-memories models. Similarly, it is argued that
      current neurological models are only phenomenologically consistent with a limited
      subset of AVHs. In contrast, the phenomenology of the majority of AVHs, which
      involve voices attempting to regulate the ongoing actions of the voice hearer,
      are argued to be more consistent with inner speech-based models. It is concluded
      that subcategorizations of AVHs may be necessary, with each underpinned by
      different neurocognitive mechanisms. The need to study what is termed the dynamic
      developmental progression of AVHs is also highlighted. Future empirical research
      is suggested in this area.

PMID- 18820263
TI  - The phenotype of human Th17 cells and their precursors, the cytokines that
      mediate their differentiation and the role of Th17 cells in inflammation.
AB  - T helper 17 (T(h)17) cells represent a new subset of CD4+ effector T cells which
      have been described in both mice and humans. However, some differences seem to
      exist between murine and human T(h)17 cells with regard to their features, origin
      and role in immunopathology. Murine T(h)17 cells share their developmental origin
      with Foxp3+ Treg cells, indeed naive T-cell precursors can be differentiated to
      regulatory T (Treg) cells by transforming growth factor-beta (TGF-beta) alone,
      whereas the contemporaneous presence of TGF-beta and IL-6 gives origin to T(h)17
      cells. Human T(h)17 cells which consistently express the CC chemokine receptor 6
      and the equivalent of the murine NK1.1, CD161, appear to exclusively originate in
      response to IL-1beta and IL-23 from a small subset of CD161+CD4+ T-cell
      precursors detectable in the thymus and in umbilical cord blood. These cells
      constitutively express the T(h)17-driving transcription factor retinoic acid
      related orphan receptor (ROR)gamma t and the IL-23R and can also give origin to
      T(h)1 cells or T(h)2 cells under the appropriate polarizing conditions. By
      contrast, human CD161-naive T cells only give rise to T(h)1 and T(h)2 cells, but
      not T(h)17 cells. TGF-beta may not exert a direct critical role in human T(h)17
      cell differentiation, but indirectly favours their development by inhibiting the
      development of T(h)1 cells, which are much more susceptible than T(h)17 cells to
      its suppressive activity on cell proliferation. Moreover, while murine T(h)17 are
      pathogenic in some murine models of autoimmunity where T(h)1 cells seem to play a
      protective role, both T(h)17 and T(h)1 certainly contribute to the pathogenesis
      of human autoimmune and other chronic inflammatory disorders.

PMID- 18820264
TI  - Impaired TCR signaling through dysfunction of lipid rafts in sphingomyelin
      synthase 1 (SMS1)-knockdown T cells.
AB  - During T cell activation, TCRs cluster at the center of the T cell-antigen
      presenting cell interface forming the central supramolecular activation cluster.
      Although it has been suggested that sphingolipid- and cholesterol-rich
      microdomains, termed lipid rafts, form platforms for the regulation and
      transduction of TCR signals, an actual role for membrane sphingomyelin (SM), a
      key component of lipid rafts, has not been reported. After cloning a gene
      responsible for SM synthesis, sphingomyelin synthase (SMS) 1, we established a SM
      knockdown cell line (Jurkat-SMS1/kd) by transfection of SMS1-short-interfering
      RNA into Jurkat T cells, which is deficient in membrane expression of SM. Upon
      CD3 stimulation, expression of CD69 (the earliest leukocyte activation antigen),
      activation-induced cell adhesion and proliferation as well as TCR clustering was
      severely impaired in Jurkat-SMS1/kd cells. CD3-induced tyrosine phosphorylation
      and association of linker for activation of T cell with ZAP-70 and Grb2 and
      phosphorylation of protein kinase C (PKC) were also severely impaired in Jurkat
      SMS1/kd cells. Finally, translocation of TCR, ZAP-70 and PKC into lipid rafts was
      markedly decreased in Jurkat-SMS1/kd cells. These findings indicate that membrane
      SM is crucial for TCR signal transduction, leading to full T cell activation
      through lipid raft function.

PMID- 18820265
TI  - Phylogenetic distances are encoded in networks of interacting pathways.
AB  - MOTIVATION: Although metabolic reactions are unquestionably shaped by
      evolutionary processes, the degree to which the overall structure and complexity
      of their interconnections are linked to the phylogeny of species has not been
      evaluated in depth. Here, we apply an original metabolome representation, termed
      Network of Interacting Pathways or NIP, with a combination of graph theoretical
      and machine learning strategies, to address this question. NIPs compress the
      information of the metabolic network exhibited by a species into much smaller
      networks of overlapping metabolic pathways, where nodes are pathways and links
      are the metabolites they exchange. RESULTS: Our analysis shows that a small set
      of descriptors of the structure and complexity of the NIPs combined into
      regression models reproduce very accurately reference phylogenetic distances
      derived from 16S rRNA sequences (10-fold cross-validation correlation coefficient
      higher than 0.9). Our method also showed better scores than previous work on
      metabolism-based phylogenetic reconstructions, as assessed by branch distances
      score, topological similarity and second cousins score. Thus, our metabolome
      representation as network of overlapping metabolic pathways captures sufficient
      information about the underlying evolutionary events leading to the formation of
      metabolic networks and species phylogeny. It is important to note that precise
      knowledge of all of the reactions in these pathways is not required for these
      reconstructions. These observations underscore the potential for the use of
      abstract, modular representations of metabolic reactions as tools in studying the
      evolution of species. SUPPLEMENTARY INFORMATION: Supplementary data are available
      at Bioinformatics online.

PMID- 18820267
TI  - Tuberculosis studies in Muscogee County, Georgia: I. Community-wide tuberculosis
      research.

PMID- 18820266
TI  - The Washington County Training Center: an exemplar of public health research in
      the field.

PMID- 18820268
TI  - Frost revisited: the modern epidemiology of tuberculosis: the third Wade Hampton
      Frost Lecture.

PMID- 18820269
TI  - Mortality of persons with photofluorograms suggestive of cardiovascular disease.

PMID- 18820270
TI  - An epidemiologic study of blood pressure levels in a biracial community in the
      Southern United States.

PMID- 18820271
TI  - Subcutaneous fatness and mortality.

PMID- 18820272
TI  - Dietary n-3 polyunsaturated acids and smoking-related chronic obstructive
      pulmonary disease.
AB  - BACKGROUND: Fish contain n-3 polyunsaturated fatty acids, principally
      eicosapentaenoic acid and docosahexaenoic acid, which are known to interfere with
      the body's inflammatory response and may be of benefit in chronic inflammatory
      conditions. METHODS: We studied the relation between the dietary intake of n-3
      fatty acids and chronic obstructive pulmonary disease (COPD) in 8960 current or
      former smokers participating in a population-based study of artheroscierosis.
      Intake of fatty acids was estimated with a dietary questionnaire. The presence of
      COPD was assessed by a questionnaire on respiratory symptoms and by spirometry.
      Three case definitions of COPD were used: symptoms of chronic bronchitis (667
      subjects), physician-diagnosed emphysema reported by the subject (185 subjects),
      and spirometrically detected COPD (197 subjects). RESULTS: After control for pack
      years of smoking, age, sex, race, height, weight, energy intake, and educational
      level docosahexaenoic acid was inversely related to the ris of COPD in a quantity
      dependent fashion. The adjusted odds ratio for the highest quartile was 0.66 for
      chronic bronchitis (95 percent confidence interval, 0.52 to 0.85; P<0.001 for
      linear trend across the range of intake value), 0.31 for physician-diagnosed
      emphysema (95 percent confidence interval, 0.18 to 0.52; P for liner trend,
      0.003), and 0.50 for spirometrically detected COPD (95 percent confidence
      interval, 0.32 to 0.79; P for linear trend, 0.007). CONCLUSION: A high dietary
      intake of n-3 fatty acids may protect cigarette smokers against COPD.

PMID- 18820273
TI  - Cigarette smoking and changes in respiratory findings.
AB  - Standardized surveys of cardiorespiratory findings were conducted among male
      telephone company employees 40 to 59 years of age, and repeated five to six years
      later. Cigarette smokers had considerably more cough, phlegm, and chronic wheeze
      and slightly more nasal catarrh and breathlessness on exertion than nonsmokers.
      Pipe and cigar smokers had intermediate levels of these symptoms. Men who quit
      cigarette smoking between two surveys showed considerable improvement in cough
      and phlegm. Respiratory symptoms and among smokers of nonfilter cigarettes.
      Forced expiratory volume decreased and sputum volume increased among all groups
      over the observation period. Both changes were least marked among men who quit
      smoking cigarettes and were most marked among those who continued to smoke
      cigarettes.

PMID- 18820274
TI  - Respiratory effects of household exposures to tobacco smoke and gas cooking.
AB  - The records of 1,724 residents of Washington County, Maryland, who had
      participated in 2 studies of respiratory symptoms and ventilatory function were
      analyzed to evaluate the effects of exposures at home to tobacco smoke generated
      by other members of their households and to fumes from the use of gas as a
      cooking fuel. Currently smoking subjects showed the highest frequency of
      respiratory symptoms and impaired ventilatory function; former smokers showed a
      lower frequency of these findings; and persons who had never smoked had the
      lowest prevalence of abnormal respiratory findings. The presence of a smoker in
      the household other than the subject was not associated with the frequency of
      respiratory symptoms, and only suggestively associated with evidence of impaired
      ventilatory function. The use of gas for cooking was related to an increased
      frequency of respiratory symptoms and impaired ventilatory function among men,
      being most marked among men who had never smoked. There was no evidence that
      cooking with gas was harmful to women.

PMID- 18820275
TI  - Church attendance and health.

PMID- 18820276
TI  - Effects of repeated freeze-thaw cycles on concentrations of cholesterol,
      micronutrients, and hormones in human plasma and serum.

PMID- 18820277
TI  - The risk of developing lung cancer associated with antioxidants in the blood:
      ascorbic acids, carotenoids, alpha-tocopherol, selenium, and total peroxyl
      radical absorbing capacity.
AB  - Lung cancer cases diagnosed during the period 1975 through 1993 and matched
      controls were identified in the rosters of Washington County, Maryland residents
      who had donated blood for a serum bank in 1974 or 1989. Plasma from participants
      in the 1989 project was assayed for ascorbic acid; serum or plasma was assayed
      for participants in either project for alpha- and beta-carotene, cryptoxanthin,
      lutein/zeaxanthin, lycopene, alpha-tocopherol, selenium, and peroxyl radical
      absorption capacity. Among the total group of 258 cases and 515 controls,
      serum/plasma concentrations were significantly lower among cases than controls
      for cryptoxanthin, beta-carotene, and lutein/zeaxanthin with case-control
      differences of -25.5, -17.1, and -10.1%, respectively. Modest nonsignificant case
      control differences in a protective direction were noted for alpha-carotene and
      ascorbic acid. There were only trivial differences for lycopene, alpha
      tocopherol, selenium, and peroxyl radical absorption capacity. Findings are
      reported for males and females and for persons who had never smoked cigarettes,
      former smokers, and current smokers at baseline. These results and those from
      previous studies suggest that beta-carotene is a marker for some protective
      factor(s) against lung cancer; that cryptoxanthin, alpha-carotene, and ascorbic
      acid need to be investigated further as potentially protective factors or
      associates of a protective factor; and that lycopene, alpha-tocopherol, selenium,
      and peroxyl radical absorption capacity are unlikely to be associated with lung
      cancer risk. Until specific preventive factors are identified, the best
      protection against lung cancer is still the avoidance of airborne carcinogens,
      especially tobacco smoke; second best is the consumption of a diet rich in fruits
      and vegetables.

PMID- 18820278
TI  - Prostate-specific antigen levels and subsequent prostate cancer: potential for
      screening.
AB  - Prostate-specific antigen levels are increased in men with prostatic disease,
      including prostate cancer, and have been used clinically to monitor the response
      of prostate cancer to therapy. More recently, prostate-specific antigen levels,
      usually in combination with digital rectal examination or transrectal prostatic
      ultrasonography, have been suggested to be useful for the detection of prostate
      cancer. To evaluate the association between a single serum prostate-specific
      antigen level and the subsequent development of prostate cancer, we measured
      serum levels in 35 men who donated blood to a community-based serum bank in 1974
      and who subsequently developed prostate cancer and in 35 matched controls from
      the same group of volunteers. Levels of prostate-specific antigen were
      significantly higher in men who went on to develop prostate cancer, up to 6 years
      prior to the time of diagnosis in the cases. The level of prostate-specific
      antigen decreased with increasing time to diagnosis. The mean level for prostate
      cancer cases diagnosed within the first 3 years of follow-up was 16.2 mug/liter
      compared to 2.4 mug/liter for controls (P = 0.002). The mean level for cancer
      cases diagnosed in years 4 through 6 following blood sampling was 9.6 mug/liter
      compared to 1.3 mug/liter for controls (p = 0.0002). The sensitivity and
      specificity of a prostate-specific antigen level >/= 4mug/liter up to 3 years
      prior to the time of clinical diagnosis were both 75% and up to 6 years were 67%
      and 85%, respectively. Because prostate-specific antigen levels are reasonably
      sensitive and specific in detecting prostate cancer up to 6 years prior to the
      time of usual diagnosis, their use in screening for the prevention of prostate
      cancer mortality should be evaluated in a controlled clinical trial.

PMID- 18820279
TI  - Rosuvastatin protects against podocyte apoptosis in vitro.
AB  - BACKGROUND: Clinical studies suggest that statins reduce proteinuria and slow the
      decline in kidney function in chronic kidney disease. Given a rich literature
      identifying podocyte apoptosis as an early step in the pathophysiological
      progression to proteinuria and glomerulosclerosis, we hypothesized that
      rosuvastatin protects podocytes from undergoing apoptosis. Regarding a potential
      mechanism, our lab has shown that the cell cycle protein, p21, has a prosurvial
      role in podocytes and there is literature showing statins upregulate p21 in other
      renal cells. Therefore, we queried whether rosuvastatin is prosurvival in
      podocytes through a p21-dependent pathway. METHODS: Two independent apoptotic
      triggers, puromycin aminonucleoside (PA) and adriamycin (ADR), were used to
      induce apoptosis in p21 +/+ and p21 -/- conditionally immortalized mouse
      podocytes with or without pre-exposure to rosuvastatin. Apoptosis was measured by
      two methods: Hoechst 33342 staining and fluorescence-activated cell sorting
      (FACS). To establish a role for p21, p21 levels were measured by western blotting
      following rosuvastatin exposure and p21 was stably transduced into p21 -/- mouse
      podocytes. RESULTS: Rosuvastatin protects against ADR- and PA-induced apoptosis
      in podocytes. Further, exposure to rosuvastatin increases p21 levels in podocytes
      in vitro. ADR induces apoptosis in p21 -/- mouse podocytes, but rosuvastatin's
      protective effect is not seen in the absence of p21. Reconstituting p21 in p21 -/
      podocytes restores rosuvastatin's prosurvival effect. CONCLUSION: Rosuvastatin
      is prosurvival in injured podocytes. Rosuvastatin exerts its protective effect
      through a p21-dependent antiapoptotic pathway. These findings suggest that
      statins decrease proteinuria by protecting against podocyte apoptosis and
      subsequent podocyte depopulation.

PMID- 18820280
TI  - Efficacy and safety of sevelamer hydrochloride and calcium acetate in patients on
      peritoneal dialysis.
AB  - BACKGROUND: Inadequate phosphorus control is associated with increased morbidity
      and mortality in patients with CKD stage 5. Although phosphate binders are often
      used in patients on peritoneal dialysis (PD), no large randomized controlled
      studies evaluating their use solely in this population have previously been
      reported. METHODS: In this multicentre, open-label study, adult patients on PD
      with serum phosphorus >5.5 mg/dl were randomized (2:1) to 12 weeks of treatment
      with sevelamer hydrochloride or calcium acetate. Doses were titrated to achieve
      serum phosphorus of 3.0-5.5 mg/dl. Changes in serum phosphorus, calcium, intact
      parathyroid hormone (iPTH), lipids and plasma biomarkers were assessed. RESULTS:
      A total of 253 patients were screened, 143 of whom were randomized (sevelamer
      hydrochloride, n = 97; calcium acetate, n = 46). Treatment groups were well
      balanced with regard to baseline demographics. Serum phosphorus levels were
      significantly reduced after 12 weeks with both sevelamer hydrochloride and
      calcium acetate (P < 0.001). Serum PTH was also reduced in both groups while
      serum calcium increased in the calcium acetate group (P = 0.001) but not in the
      sevelamer hydrochloride group. Sevelamer hydrochloride was also associated with
      decreases in total cholesterol, low-density lipoprotein cholesterol and uric acid
      and an increase in bone-specific alkaline phosphatase (all P < 0.001 versus
      baseline). Both treatments were well tolerated and safety profiles were
      consistent with previous reports in haemodialysis patients. Hypercalcaemia was
      experienced by more calcium acetate-treated patients (18 versus 2%; P = 0.001).
      CONCLUSIONS: In summary, sevelamer hydrochloride provides a reduction in serum
      phosphorus compared to that obtained with calcium-based binders in PD patients.
      The effects of sevelamer hydrochloride appear similar in both PD and
      haemodialysis populations.

PMID- 18820281
TI  - Does TNF-alpha enhance cystogenesis in ADPKD?

PMID- 18820282
TI  - The CARE-2 study results: setting the record straight.

PMID- 18820283
TI  - Association of hsp90 to the hTERT promoter is necessary for hTERT expression in
      human oral cancer cells.
AB  - Enhanced expression of human telomerase reverse transcriptase (hTERT) occurs
      frequently during cellular immortalization. The current study was undertaken to
      determine the mechanism regulating the hTERT promoter activity during cellular
      immortalization of human oral keratinocytes. Normal human oral keratinocytes
      (NHOKs) were immortalized with Bmi-1 and the E6 oncoprotein of human
      papillomavirus type 16 to establish the telomerase-positive HOK-Bmi-1/E6 cell
      line. Using DNA-protein-binding assay, we found that heat shock protein 90
      (hsp90) physically interacts with the hTERT promoter in vitro. The hsp90
      interaction with the promoter was detected more strongly in the telomerase
      positive HOK-Bmi-1/E6 cells compared with that in senescing NHOK. Chromatin
      immunoprecipitation confirmed the in vivo interaction between hsp90 and the hTERT
      promoter in SCC4 cells, a telomerase-positive oral cancer cell line, but not in
      the NHOK. To determine the physiological significance of this interaction, SCC4
      cells were exposed to geldanamycin (GA), a competitive inhibitor of hsp90. GA
      exposure led to decrease in telomerase activity, hTERT promoter activity and
      hTERT messenger RNA expression in SCC4 cells, even in the absence of de novo
      protein synthesis. Also, it abolished the in vivo interaction of the hTERT
      promoter region with hsp90 but not with Sp1 or c-Myc. These results indicate that
      physical interaction between hsp90 and the hTERT promoter occurs in telomerase
      positive cells but not in normal human cells and is necessary for the enhanced
      hTERT expression and telomerase activity in cancer cells.

PMID- 18820284
TI  - Treatment of mice with the Ah receptor agonist and human carcinogen dioxin
      results in altered numbers and function of hematopoietic stem cells.
AB  - The aryl hydrocarbon receptor (AhR) mediates the carcinogenicity of a family of
      environmental contaminants, the most potent being 2,3,7,8-tetrachlorodibenzo-p
      dioxin (TCDD). Increased incidence of lymphoma and leukemia in humans is
      associated with TCDD exposure. Although AhR activation by TCDD has profound
      effects on the immune system, precise cellular and molecular mechanisms have yet
      to be determined. These studies tested the hypothesis that alteration of marrow
      populations following treatment of mice with TCDD is due to an effect on
      hematopoietic stem cells (HSCs). Treatment with TCDD resulted in an increased
      number and proliferation of bone marrow (BM) populations enriched for HSCs. There
      was a time-dependent decrease in B-lineage cells with a concomitant increase in
      myeloid populations. The decrease in the B-cell lineage colony-forming unit-preB
      progenitors along with a transient increase in myeloid progenitors were
      consistent with a skewing of lineage development from lymphoid to myeloid
      populations. However, HSCs from TCDD-treated mice exhibited diminished capacity
      to reconstitute and home to marrow of irradiated recipients. AhR messenger RNA
      was expressed in progenitor subsets but is downregulated during HSC
      proliferation. This result was consistent with the lack of response following the
      exposure of 5-fluorouracil-treated mice to TCDD. The direct exposure of cultured
      BM cells to TCDD inhibited the growth of immature hematopoietic progenitor cells,
      but not more mature lineage-restricted progenitors. Overall, these data are
      consistent with the hypothesis that TCDD, through AhR activation, alters the
      ability of HSCs to respond appropriately to signals within the marrow
      microenvironment.

PMID- 18820285
TI  - Analysis of ABCG2 expression and side population identifies intrinsic drug efflux
      in the HCC cell line MHCC-97L and its modulation by Akt signaling.
AB  - Active drug efflux by the adenosine triphosphate-binding cassette (ABC)
      transporter ABCG2 is one of the common mechanisms causing multiple drug
      resistance in various human cancers. In the intrinsic drug resistance of
      hepatocellular carcinoma (HCC), the role of ABCG2 is closely associated with
      'side population (SP)', a minor subset of cancer stem-like cells with unique
      capacity to extrude lipophilic dye Hoechst 33342 and many chemotherapeutic
      agents. In this study, we showed that ABCG2 was intrinsically expressed in a
      subgroup of HCC tissues and its expression pattern significantly influenced the
      levels of drug efflux from HCC cell lines. In MHCC-97L HCC cell line with
      intrinsic ABCG2 expression, we confirmed the importance of SP cells to the drug
      efflux-related chemotherapy resistance and found that the SP analysis provided an
      efficient method to evaluate the functional activity of ABCG2 transporter. In
      this cell line, we discovered that the SP proportion was modulated by the
      treatments of Akt signaling inhibitors and serum supplement, which led to the
      finding that Akt signaling was able to regulate the SP cells' efflux activity via
      altering the subcellular localization of ABCG2 transporter. We further
      demonstrated that the Akt signaling inhibition attenuated the doxorubicin efflux
      from MHCC-97L cells and increased the drug efficacy. Our results indicate the
      protective role of intrinsic ABCG2 expression in HCC cells and suggest that
      suppressing Akt signaling could help overcome the drug efflux by ABCG2
      transporter.

PMID- 18820286
TI  - Anti-inflammatory and antitumor promotional effects of a novel urinary
      metabolite, 3',4'-didemethylnobiletin, derived from nobiletin.
AB  - We reported previously that 3',4'-didemethylnobiletin (DDMN) is the major
      metabolite of nobiletin in mouse urine. In this study, we examined DDMN's
      molecular mechanism of action and its anti-inflammatory and antitumor properties.
      We demonstrated that topical application of DDMN effectively inhibited 12-O
      tetradecanoylphorbol-13-acetate (TPA)-stimulated transcription of inducible
      nitric oxide synthase (iNOS), cyclooxygenase (COX)-2 and ornithine decarboxylase
      (ODC) messenger RNA and protein expression in mouse skin. Pretreatment with DDMN
      has resulted in the reduction of TPA-induced nuclear translocation of the nuclear
      factor-kappa B (NF-kappaB) subunit. DDMN also reduced DNA binding by blocking
      phosphorylation of inhibitor kappaB (IkappaB) alpha and p65 and caused subsequent
      degradation of IkappaBalpha. DDMN inhibited TPA-induced phosphorylation and
      nuclear translocation of the signal transducer and activator of transcription 3.
      Moreover, DDMN suppressed TPA-induced activation of extracellular signal
      regulated kinase 1/2, p38 mitogen-activated protein kinase, phosphatidylinositol
      3-kinase/Akt and protein kinase C that are upstream of NF-kappaB and activator
      protien-1. We also found that DDMN significantly inhibited TPA-induced mouse skin
      inflammation by decreasing inflammatory parameters. Furthermore, DDMN
      significantly inhibited 7,12-dimethylbenz[a]anthracene/TPA-induced skin tumor
      formation measured by the tumor multiplicity of papillomas at 20 weeks. Presented
      data for the first time reveal that DDMN is an effective antitumor agent that
      functions by downregulating inflammatory iNOS, COX-2 and ODC gene expression in
      mouse skin. It is suggested that DDMN is a novel functional agent capable of
      preventing inflammation-associated tumorigenesis.

PMID- 18820287
TI  - Molecular regulation of DNA damage-induced apoptosis in neurons of cerebral
      cortex.
AB  - Cerebral cortical neuron degeneration occurs in brain disorders manifesting
      throughout life, but the mechanisms are understood poorly. We used cultured
      embryonic mouse cortical neurons and an in vivo mouse model to study mechanisms
      of DNA damaged-induced apoptosis in immature and differentiated neurons. p53
      drives apoptosis of immature and differentiated cortical neurons through its
      rapid and prominent activation stimulated by DNA strand breaks induced by
      topoisomerase-I and -II inhibition. Blocking p53-DNA transactivation with alpha
      pifithrin protects immature neurons; blocking p53-mitochondrial functions with mu
      pifithrin protects differentiated neurons. Mitochondrial death proteins are
      upregulated in apoptotic immature and differentiated neurons and have
      nonredundant proapoptotic functions; Bak is more dominant than Bax in
      differentiated neurons. p53 phosphorylation is mediated by ataxia telangiectasia
      mutated (ATM) kinase. ATM inactivation is antiapoptotic, particularly in
      differentiated neurons, whereas inhibition of c-Abl protects immature neurons but
      not differentiated neurons. Cell death protein expression patterns in mouse
      forebrain are mostly similar to cultured neurons. DNA damage induces prominent
      p53 activation and apoptosis in cerebral cortex in vivo. Thus, DNA strand breaks
      in cortical neurons induce rapid p53-mediated apoptosis through actions of
      upstream ATM and c-Abl kinases and downstream mitochondrial death proteins. This
      molecular network operates through variations depending on neuron maturity.

PMID- 18820288
TI  - Smooth pursuit-related information processing in frontal eye field neurons that
      project to the NRTP.
AB  - The cortical pursuit system begins the process of transforming visual signals
      into commands for smooth pursuit (SP) eye movements. The frontal eye field (FEF),
      located in the fundus of arcuate sulcus, is known to play a role in SP and gaze
      pursuit movements. This role is supported, at least in part, by FEF projections
      to the rostral nucleus reticularis tegmenti pontis (rNRTP), which in turn
      projects heavily to the cerebellar vermis. However, the functional
      characteristics of SP-related FEF neurons that project to rNRTP have never been
      described. Therefore, we used microelectrical stimulation (ES) to deliver single
      pulses (50-200 microA, 200-micros duration) in rNRTP to antidromically activate
      FEF neurons. We estimated the eye or retinal error motion sensitivity (position,
      velocity, and acceleration) of FEF neurons during SP using multiple linear
      regression modeling. FEF neurons that projected to rNRTP were most sensitive to
      eye acceleration. In contrast, FEF neurons not activated following ES of rNRTP
      were often most sensitive to eye velocity. In similar modeling studies, we found
      that rNRTP neurons were also biased toward eye acceleration. Therefore, our
      results suggest that neurons in the FEF-rNRTP pathway carry signals that could
      play a primary role in initiation of SP.

PMID- 18820289
TI  - Event congruency enhances episodic memory encoding through semantic elaboration
      and relational binding.
AB  - Behavioral research consistently shows that congruous events, that is, events
      whose constituent elements match along some specific dimension, are better
      remembered than incongruous events. Although it has been speculated that this
      "congruency subsequent memory effect" (cSME) results from enhanced semantic
      elaboration, empirical evidence for this account is lacking. Here, we report a
      set of behavioral and neuroimaging experiments demonstrating that congruous
      events engage regions along the left inferior frontal gyrus (LIFG)--consistently
      related to semantic elaboration--to a significantly greater degree than
      incongruous events, providing evidence in favor of this hypothesis. Critically,
      we additionally report 3 novel findings in relation to event congruency: First,
      congruous events yield superior memory not only for a given study item but also
      for associated source details. Second, the cSME is evident not only for events
      that matched a semantic context but also for those that matched a subjective
      aesthetic schema. Finally, functional magnetic resonance imaging brain/behavior
      correlation analysis reveals a strong link between 1) across-subject variation in
      the magnitude of the cSME and 2) differential right hippocampal activation,
      suggesting that episodic memory for congruous events is effectively bolstered by
      the extent to which semantic associations are generated and relationally
      integrated via LIFG-hippocampal-encoding mechanisms.

PMID- 18820290
TI  - A dual role for prediction error in associative learning.
AB  - Confronted with a rich sensory environment, the brain must learn statistical
      regularities across sensory domains to construct causal models of the world.
      Here, we used functional magnetic resonance imaging and dynamic causal modeling
      (DCM) to furnish neurophysiological evidence that statistical associations are
      learnt, even when task-irrelevant. Subjects performed an audio-visual target
      detection task while being exposed to distractor stimuli. Unknown to them,
      auditory distractors predicted the presence or absence of subsequent visual
      distractors. We modeled incidental learning of these associations using a
      Rescorla-Wagner (RW) model. Activity in primary visual cortex and putamen
      reflected learning-dependent surprise: these areas responded progressively more
      to unpredicted, and progressively less to predicted visual stimuli. Critically,
      this prediction-error response was observed even when the absence of a visual
      stimulus was surprising. We investigated the underlying mechanism by embedding
      the RW model into a DCM to show that auditory to visual connectivity changed
      significantly over time as a function of prediction error. Thus, consistent with
      predictive coding models of perception, associative learning is mediated by
      prediction-error dependent changes in connectivity. These results posit a dual
      role for prediction-error in encoding surprise and driving associative
      plasticity.

PMID- 18820291
TI  - A token economy for exercise adherence in pediatric cystic fibrosis: a single
      subject analysis.
AB  - OBJECTIVE: In cystic fibrosis (CF), adherence to airway clearance techniques
      (e.g., chest physiotherapy and exercise) is poor. Exercise is important because
      pulmonary difficulties are associated with the highest mortality rate. Despite
      this, very little research has focused on exercise adherence in CF. This study
      examined a token economy for increasing exercise in children with CF. METHODS: An
      ABAB single-subject design evaluated a token economy for increasing and
      maintaining exercise in three children with CF. Patient report, parent report,
      and physiological measures were used to assess treatment integrity, medical
      stability, and changes in exercise. RESULTS: Measures suggested that treatment
      integrity was strong. Results indicated strong treatment effects for all
      participants without negative medical side effects. Follow-up of 1 and 3 months
      supported continued exercise for all participants. CONCLUSIONS: A token economy
      effectively increased exercise in children with CF, and the single-subject design
      highlighted some of the intricacies of individualized treatment of adherence.
      Implications and recommendations for further research are discussed.

PMID- 18820292
TI  - RiceGeneThresher: a web-based application for mining genes underlying QTL in rice
      genome.
AB  - RiceGeneThresher is a public online resource for mining genes underlying genome
      regions of interest or quantitative trait loci (QTL) in rice genome. It is a
      compendium of rice genomic resources consisting of genetic markers, genome
      annotation, expressed sequence tags (ESTs), protein domains, gene ontology, plant
      stress-responsive genes, metabolic pathways and prediction of protein-protein
      interactions. RiceGeneThresher system integrates these diverse data sources and
      provides powerful web-based applications, and flexible tools for delivering
      customized set of biological data on rice. Its system supports whole-genome gene
      mining for QTL by querying using DNA marker intervals or genomic loci.
      RiceGeneThresher provides biologically supported evidences that are essential for
      targeting groups or networks of genes involved in controlling traits underlying
      QTL. Users can use it to discover and to assign the most promising candidate
      genes in preparation for the further gene function validation analysis. The web
      based application is freely available at http://rice.kps.ku.ac.th.

PMID- 18820293
TI  - Nuclear export competence of pre-40S subunits in fission yeast requires the
      ribosomal protein Rps2.
AB  - Ribosome biogenesis is an evolutionarily conserved pathway that requires
      ribosomal and nonribosomal proteins. Here, we investigated the role of the
      ribosomal protein S2 (Rps2) in fission yeast ribosome synthesis. As for many
      budding yeast ribosomal proteins, Rps2 was essential for cell viability in
      fission yeast and the genetic depletion of Rps2 caused a complete inhibition of
      40S ribosomal subunit production. The pattern of pre-rRNA processing upon
      depletion of Rps2 revealed a reduction of 27SA(2) pre-rRNAs and the concomitant
      production of 21S rRNA precursors, consistent with a role for Rps2 in efficient
      cleavage at site A(2) within the 32S pre-rRNA. Importantly, kinetics of pre-rRNA
      accumulation as determined by rRNA pulse-chases assays indicated that a small
      fraction of 35S precursors matured into 20S-containing particles, suggesting that
      most 40S precursors were rapidly degraded in the absence of Rps2. Analysis of
      steady-state RNA levels revealed that some pre-40S particles were produced in
      Rps2-depleted cells, but that these precursors were retained in the nucleolus.
      Our findings suggest a role for Rps2 in a mechanism that monitors pre-40S export
      competence.

PMID- 18820294
TI  - Human SWI/SNF directs sequence-specific chromatin changes on promoter
      polynucleosomes.
AB  - Studies in humans and other species have revealed that a surprisingly large
      fraction of nucleosomes adopt specific positions on promoters, and that these
      positions appear to be determined by nucleosome positioning DNA sequences (NPSs).
      Recent studies by our lab, using minicircles containing only one nucleosome,
      indicated that the human SWI/SNF complex (hSWI/SNF) prefers to relocate
      nucleosomes away from NPSs. We now make use of novel mapping techniques to
      examine the hSWI/SNF sequence preference for nucleosome movement in the context
      of polynucleosomal chromatin, where adjacent nucleosomes can limit movement and
      where hSWI/SNF forms altered dinucleosomal structures. Using two NPS templates
      (5S rDNA and 601) and two hSWI/SNF target promoter templates (c-myc and UGT1A1),
      we observed hSWI/SNF-driven depletion of normal mononucleosomes from almost all
      positions that were strongly favored by assembly. In some cases, these
      mononucleosomes were moved to hSWI/SNF-preferred sequences. In the majority of
      other cases, one repositioned mononucleosome appeared to combine with an unmoved
      mononucleosome forming a specifically localized altered or normal dinucleosome.
      These effects result in dramatic, template-specific changes in nucleosomal
      distribution. Taken together, these studies indicate hSWI/SNF is likely to
      activate or repress transcription of its target genes by generating promoter
      sequence-specific changes in chromatin configuration.

PMID- 18820295
TI  - How PspGI, catalytic domain of EcoRII and Ecl18kI acquire specificities for
      different DNA targets.
AB  - Restriction endonucleases Ecl18kI and PspGI/catalytic domain of EcoRII recognize
      CCNGG and CCWGG sequences (W stands for A or T), respectively. The enzymes are
      structurally similar, interact identically with the palindromic CC:GG parts of
      their recognition sequences and flip the nucleotides at their centers.
      Specificity for the central nucleotides could be influenced by the
      strength/stability of the base pair to be disrupted and/or by direct interactions
      of the enzymes with the flipped bases. Here, we address the importance of these
      contributions. We demonstrate that wt Ecl18kI cleaves oligoduplexes containing
      canonical, mismatched and abasic sites in the central position of its target
      sequence CCNGG with equal efficiencies. In contrast, substitutions in the binding
      pocket for the extrahelical base alter the Ecl18kI preference for the target
      site: the W61Y mutant prefers only certain mismatched substrates, and the W61A
      variant cuts exclusively at abasic sites, suggesting that pocket interactions
      play a major role in base discrimination. PspGI and catalytic domain of EcoRII
      probe the stability of the central base pair and the identity of the flipped
      bases in the pockets. This 'double check' mechanism explains their extraordinary
      specificity for an A/T pair in the flipping position.

PMID- 18820296
TI  - Identification of the Xenopus DNA2 protein as a major nuclease for the 5'->3'
      strand-specific processing of DNA ends.
AB  - The first step of homology-dependent DNA double-strand break (DSB) repair is the
      5' strand-specific processing of DNA ends to generate 3' single-strand tails.
      Despite extensive effort, the nuclease(s) that is directly responsible for the
      resection of 5' strands in eukaryotic cells remains elusive. Using nucleoplasmic
      extracts (NPE) derived from the eggs of Xenopus laevis as the model system, we
      have found that DNA processing consists of at least two steps: an ATP-dependent
      unwinding of ends and an ATP-independent 5'-->3' degradation of single-strand
      tails. The unwinding step is catalyzed by DNA helicases, the major one of which
      is the Xenopus Werner syndrome protein (xWRN), a member of the RecQ helicase
      family. In this study, we report the purification and identification of the
      Xenopus DNA2 (xDNA2) as one of the nucleases responsible for the 5'-->3'
      degradation of single-strand tails. Immunodepletion of xDNA2 resulted in a
      significant reduction in end processing and homology-dependent DSB repair. These
      results provide strong evidence that xDNA2 is a major nuclease for the resection
      of DNA ends for homology-dependent DSB repair in eukaryotes.

PMID- 18820297
TI  - Regulation of the catalytic function of topoisomerase II alpha through
      association with RNA.
AB  - Topoisomerase IIalpha interacts with numerous nuclear factors, through which it
      is engaged in diverse nuclear events such as DNA replication, transcription and
      the formation or maintenance of heterochromatin. We previously reported that
      topoisomerase IIalpha interacts with RNA helicase A (RHA), consistent with a
      recent view that topoisomerases and helicases function together. Intrigued by our
      observation that the RHA-topoisomerase IIalpha interaction is sensitive to
      ribonuclease A, we explored whether the RHA-topoisomerase IIalpha interaction can
      be recapitulated in vitro using purified proteins and a synthetic RNA. This work
      led us to an unexpected finding that an RNA-binding activity is intrinsically
      associated with topoisomerase IIalpha. Topoisomerase IIalpha stably interacted
      with RNA harboring a 3'-hydroxyl group but not with RNA possessing a 3'-phosphate
      group. When measured in decatenation and relaxation assays, RNA binding
      influenced the catalytic function of topoisomerase IIalpha to regulate DNA
      topology. We discuss a possible interaction of topoisomerase IIalpha with the
      poly(A) tail and G/U-rich 3'-untranslated region (3'-UTR) of mRNA as a key step
      in transcription termination.

PMID- 18820298
TI  - Sumoylation of LAP1 is involved in the HDAC4-mediated repression of COX-2
      transcription.
AB  - CEBPB, one of the CEBP family members, is a crucial regulator of gene expression
      during innate immunity, inflammatory responses and adipogenesis. In this study,
      the EGF-induced increase of CEBPB mRNA is shown to be coincident with the
      decrease of COX-2 mRNA. We identified that all of the individual CEBPB isoforms,
      LAP1, LAP2 and LIP, attenuate EGF-induced COX-2 promoter activity. Although
      increased sumoylation of both LAP1 and LAP2 is observed during the lagging stage
      of EGF treatment, only the sumoylated LAP1, but not the sumoylated LAP2, is
      responsible for COX-2 gene repression. In addition, EGF treatment can regulate
      the nucleocytoplasmic redistribution of HDAC4 and SUMO1. We further demonstrated
      by loss-of- and gain-of-function approaches that HDAC4 can be a negative
      regulator while inactivating COX-2 transcription. The sumoylation mutant LAP1,
      LAP1K174A, exhibits an attenuated ability to interact with HDAC4, and increased
      COX-2 promoter activity. Furthermore, the in vivo DNA binding assay demonstrated
      that LAP1K174A and CEBPDK120A, sumoylation-defective CEBPD mutants, attenuate the
      binding of HDAC4 on the COX-2 promoter. In light of the above, our data suggest
      that the suCEBPD and suLAP1 are involved in the repression of COX-2 transcription
      through the recruitment of HDAC4.

PMID- 18820299
TI  - Evolutionary conservation supports ancient origin for Nudt16, a nuclear
      localized, RNA-binding, RNA-decapping enzyme.
AB  - Nudt16p is a nuclear RNA decapping protein initially identified in Xenopus (X29)
      and known to exist in mammals. Here, we identified putative orthologs in 57
      different organisms ranging from humans to Cnidaria (anemone/coral). In vitro
      analysis demonstrated the insect ortholog can bind RNA and hydrolyze the m(7)G
      cap from the 5'-end of RNAs indicating the Nudt16 gene product is functionally
      conserved across metazoans. This study also identified a closely related
      paralogous protein, known as Syndesmos, which resulted from a gene duplication
      that occurred in the tetrapod lineage near the amniote divergence. While
      vertebrate Nudt16p is a nuclear RNA decapping protein, Syndesmos is associated
      with the cytoplasmic membrane in tetrapods. Syndesmos is inactive for RNA
      decapping but retains RNA-binding activity. This structure/function analysis
      demonstrates evolutionary conservation of the ancient Nudt16 protein suggesting
      the existence and maintenance of a nuclear RNA degradation pathway in metazoans.

PMID- 18820300
TI  - Long intronic GAA*TTC repeats induce epigenetic changes and reporter gene
      silencing in a molecular model of Friedreich ataxia.
AB  - Friedreich ataxia (FRDA) is caused by hyperexpansion of GAA*TTC repeats located
      in the first intron of the FXN gene, which inhibits transcription leading to the
      deficiency of frataxin. The FXN gene is an excellent target for therapeutic
      intervention since (i) 98% of patients carry the same type of mutation, (ii) the
      mutation is intronic, thus leaving the FXN coding sequence unaffected and (iii)
      heterozygous GAA*TTC expansion carriers with approximately 50% decrease of the
      frataxin are asymptomatic. The discovery of therapeutic strategies for FRDA is
      hampered by a lack of appropriate molecular models of the disease. Herein, we
      present the development of a new cell line as a molecular model of FRDA by
      inserting 560 GAA*TTC repeats into an intron of a GFP reporter minigene. The
      GFP_(GAA*TTC)(560) minigene recapitulates the molecular hallmarks of the mutated
      FXN gene, i.e. inhibition of transcription of the reporter gene, decreased levels
      of the reporter protein and hypoacetylation and hypermethylation of histones in
      the vicinity of the repeats. Additionally, selected histone deacetylase
      inhibitors, known to stimulate the FXN gene expression, increase the expression
      of the GFP_(GAA*TTC)(560) reporter. This FRDA model can be adapted to high
      throughput analyses in a search for new therapeutics for the disease.

PMID- 18820301
TI  - Stress-induced tRNA-derived RNAs: a novel class of small RNAs in the primitive
      eukaryote Giardia lamblia.
AB  - Giardia lamblia is an early diverging and evolutionarily successful protozoan as
      it can enter into a dormant cyst stage from a vegetative trophozoite. During
      dormant stage, its metabolic rate decreases dramatically. However, to date, the
      regulatory molecules participating in the initiation and maintenance of this
      process have not been fully investigated. In this study, we have identified a
      class of abundant small RNAs named sitRNAs, which are approximately 46
      nucleotides in length and accumulate in G. lamblia encysting cultures.
      Remarkably, they are derived from the 3' portion of fully matured tRNAs by
      cleavage of the anticodon left arm, with the 3' terminal CCA triplex still
      connected. During differentiation, only a limited portion of mature tRNAs is
      cleaved, but this cleavage occurs almost in the entire tRNA family. sitRNAs begin
      to accumulate as early as 3 h after initiation of encystation and are maintained
      at a relatively stable level during the whole process, exhibiting an expression
      peak at around 24 hr. Our studies further show that sitRNAs can be induced by
      several other stress factors, and in the case of serum deprivation, both tRNAs
      and sitRNAs degrade rapidly, with the accumulation of tRNA being halved. Our
      results may provide new insight into a novel mechanism for stressed G. lamblia to
      regulate gene expression globally.

PMID- 18820302
TI  - MECP2 genomic structure and function: insights from ENCODE.
AB  - MECP2, a relatively small gene located in the human X chromosome, was initially
      described with three exons transcribing RNA from which the protein MeCP2 was
      translated. It is now known to have four exons from which two isoforms are
      translated; however, there is also evidence of additional functional genomic
      structures within MECP2, including exons potentially transcribing non-coding
      RNAs. Accompanying the recognition of a higher level of intricacy within MECP2
      has been a recent surge of knowledge about the structure and function of human
      genes more generally, to the extent that the definition of a gene is being
      revisited. It is timely now to review the published and novel functional elements
      within MECP2, which is proving to have a complexity far greater than was
      previously thought.

PMID- 18820303
TI  - KnotInFrame: prediction of -1 ribosomal frameshift events.
AB  - Programmed -1 ribosomal frameshift (-1 PRF) allows for alternative reading frames
      within one mRNA. First found in several viruses, it is now believed to exist in
      all kingdoms of life. Strong stimulators for -1 PRF are a heptameric slippery
      site and an RNA pseudoknot. Here, we present a new algorithm KnotInFrame, for the
      automatic detection of -1 PRF signals from genomic sequences. It finds the
      frameshifting stimulators by means of a specialized RNA-pseudoknot folding
      program, fast enough for genome-wide analyses. Evaluations on known -1 PRF
      signals demonstrate a high sensitivity.

PMID- 18820304
TI  - Literature mining in support of drug discovery.
AB  - The drug discovery enterprise provides strong drivers for data integration. While
      attention in this arena has tended to focus on integration of primary data from
      omics and other large platform technologies contributing to drug discovery and
      development, the scientific literature remains a major source of information
      valuable to pharmaceutical enterprises, and therefore tools for mining such data
      and integrating it with other sources are of vital interest and economic impact.
      This review provides a brief overview of approaches to literature mining as they
      relate to drug discovery, and offers an illustrative case study of a
      'lightweight' approach we have implemented within an industrial context.

PMID- 18820305
TI  - A cephalometric intercentre comparison of patients with unilateral cleft lip and
      palate at 5 and 10 years of age.
AB  - The aim of this study was to evaluate any differences between the craniofacial
      growth of unilateral cleft lip and palate (UCLP) patients who underwent surgery
      in the Milan CLP centre with those from the Oslo CLP centre at 5 and 10 years of
      age. The Milan sample comprised 88 UCLP patients (60 males, 28 females) at 5
      years of age and 26 patients (17 males, 9 females) at 10 years of age all
      operated on by the same surgeon. The Oslo sample consisted of 48 UCLP patients
      (26 males, 22 females) aged 5 years and 29 patients (20 males, 9 females) aged 10
      years treated by four different surgeons. Lateral cephalometric radiographs
      obtained for both samples were analysed and angular measurements and ratios were
      calculated both for the hard and soft tissues. Statistical analysis was
      undertaken with an unpaired t-test. At 5 years of age, there were neither
      sagittal nor vertical hard tissue differences between the two groups. With regard
      to the soft tissues, only the naso-labial angle showed a statistically
      significant difference (Milan greater than Oslo by 5 degrees, P < 0.01). At 10
      years of age, both SNA and ANB differences were larger in the Oslo group than in
      the Milan group, >2.6 degrees, P < 0.01 and >2.9 degrees, P < 0.001,
      respectively. At 5 years of age, the Milan UCLP sample had the same maxillary
      protrusion as the Oslo group, while at 10 years of age, the Milan sample were
      slightly less protruded than the Oslo group.

PMID- 18820306
TI  - Treatment effects of intraoral appliances with conventional anchorage designs for
      non-compliance maxillary molar distalization: a literature review.
AB  - Since the end of the 1970s, various appliances with intramaxillary anchorage for
      distalization of the upper molars have been described as an alternative to
      headgear. The major advantages of these innovative appliances are that they act
      permanently and are independent of patient compliance. The purpose of this study
      was to compare the efficiency, both quantitatively and qualitatively, of various
      appliance types with intramaxillary anchorage for non-compliance molar
      distalization. Eighty-five papers were reviewed, and 22 were identified as being
      suitable for inclusion. The selection was based on compliance with the following
      criteria: treatment group with at least 10 non-syndromal patients, conventional
      intraoral anchorage design using a palatal button and anchorage teeth, consistent
      cephalometric measurements in clinical-epidemiological studies, exact data on the
      course of treatment, and statistical presentation of the measured outcomes and
      their standard deviations. The results show that non-compliance molar
      distalization is possible with numerous different appliances. While molar
      distalization with standard pendulum appliances exhibited the largest values for
      dental-linear distalization, it also resulted in concurrent, substantial
      therapeutically undesirable distal tipping. However, specific modifications to
      the pendulum appliance allow achievement of almost bodily molar distalization.
      Different outcomes are quoted in the studies for the efficiency of loaded spring
      systems for distal molar movement, but it seems that the first class appliance
      and the palatal distal jet are more efficient than the vestibular Jones Jig. The
      studies identify anchorage loss as being found in the area of the incisors rather
      than the area of the first premolars. There was a trend for more substantial
      reciprocal side-effects to occur when only two teeth were included in the
      anchorage unit. Vertical components acting on the molars, premolars, and
      incisors, such as intrusion and extrusion, tended to be of secondary importance
      and, therefore, may be disregarded.

PMID- 18820307
TI  - A comparison of physicians' end-of-life decision making for non-western migrants
      and Dutch natives in the Netherlands.
AB  - BACKGROUND: Non-western migrants have a different cultural background that
      influences their attitudes towards healthcare. As the first wave of this
      relatively young group is growing older, we investigated, for the first time,
      whether end-of-life decision-making practices for non-western migrants differ
      from Dutch natives. METHODS: In 2005, we sent questionnaires to physicians who
      attended deaths identified from the central death registry of Statistics
      Netherlands (n = 9651; non-western migrants: n = 627, total response: 78%). We
      performed multivariate logistic regression analyses adjusted for age, sex and
      cause of death. RESULTS: Of all deaths of non-western origin, 54% were non
      sudden, whereas 67% of all deaths with a Dutch origin were non-sudden (P = 0.00).
      A relatively large number of non-suddenly deceased persons of non-western origin
      had died under the age of 65 (53%) as compared to Dutch natives (15%). Euthanasia
      was performed in 2.4% of all non-suddenly deceased persons in the non-western
      migrant group as compared to 2.7% in the native Dutch group (adjusted odds ratio
      = 0.82, P = 0.63). Alleviation of symptoms with a potential life-shortening
      effect was somewhat lower for non-western migrants (30% vs. 38%; adjusted odds
      ratio = 0.78, P = 0.07). Physicians decided to forgo potentially life-prolonging
      treatment in comparable rates (26% vs. 23%; adjusted odds ratio = 1.1, P = 0.73).
      Yet, the type of treatments forgone and underlying reasons differed. CONCLUSION:
      Euthanasia was not less common among non-suddenly deceased non-western migrants
      as compared to Dutch natives. However, intensive symptom alleviation was used
      less frequently and forgoing potentially life-prolonging treatment involved
      different characteristics. These findings suggest that cultural factors may
      affect end-of-life decision making.

PMID- 18820308
TI  - Smoking and related factors of the social environment among adolescents in the
      Republic of Karelia, Russia in 1995 and 2004.
AB  - BACKGROUND: To investigate changes in smoking prevalence associated with social
      factors and existing health policies among adolescents in Russia from 1995 to
      2004. METHODS: In 1995 and 2004 a confidential questionnaire was distributed to
      every 9th grade student of all 10 comprehensive schools of the Pitkaranta in
      Republic of Karelia, Russia. In 1995, 385 children participated in the survey
      (response rate 95%) and 395 children (response rate 85%) in 2004. RESULTS: Twenty
      nine percent of boys smoked daily in 1995 and 31% in 2004. Daily smoking doubled
      from 7% to 15% for girls. Smoking in the schoolyard increased among girls. The
      proportion of girls who reported smoking at home with their parents' knowledge
      increased. Both genders cited the ease of purchasing tobacco as a minor.
      Knowledge about the fast development of tobacco addiction increased statistically
      significantly among boys. Fewer numbers of respondents of either gender thought
      that young smokers look 'cool' and more grown up. Having a best friend who smoked
      was the strongest predictor for smoking for both genders. CONCLUSION: Smoking has
      increased among girls. Social environment is a predisposing factor. Anti-smoking
      legislation was implemented weakly. Minors purchase tobacco relatively easily.
      Knowledge about tobacco's harmfulness has somewhat increased but is not
      sufficient to deter starting smoking, especially among non-smoking girls.
      Adequate education of adolescents on the hazards of tobacco consumption is
      needed, accompanied by a more determined enforcement of health policies. The
      potent influence of peers should be considered when planning preventive
      interventions.

PMID- 18820309
TI  - High circulating levels of VEGF-C suggest abnormal lymphangiogenesis in systemic
      sclerosis.

PMID- 18820310
TI  - Shoulder acute pain in primary healthcare: is retraining effective for GP
      principals? SAPPHIRE--a randomized controlled trial.
AB  - OBJECTIVE: To address the question whether general practitioners (GPs) should
      receive practical training in shoulder problems and to test whether cortisone
      injections are better than anaesthetic injections for rotator cuff problems.
      METHODS: A pragmatic split-plot, randomized trial with a cluster factorial
      design, conducted in general practices across five centres across the United
      Kingdom. Ninety-one practices were randomized to receive additional training in
      diagnosing and injecting rotator cuff problems or no additional training. Two
      hundred patients consulting their general practices with shoulder pain were then
      randomized to receive either a corticosteroid or lignocaine injection. The main
      outcome was score on the British Shoulder Disability Questionnaire (BSDQ). The
      Short-Form 36-item Health Survey and EuroQol at 12 months from entry to the trial
      were also scored. RESULTS: Over the course of the trial there was a mean
      difference of 0.94 (s.e. = 1.01) on the BSDQ score between the groups, with
      patients treated by the untrained group having a mean of 9.46 (s.e. = 0.82) and
      those by the trained group having a mean of 8.51 (s.e. = 0.60). There were no
      statistically significant differences between the groups. Analysing by substance
      injected, there was a mean difference of 0.15 (s.e. = 0.48) throughout the trial
      between the groups, with patients given the cortisone having a mean BSDQ of 9.67
      (s.e. = 0.39) and those given lignocaine, 9.82 (s.e. = 0.39). This was not
      statistically significantly different. CONCLUSIONS: Training GPs in the diagnosis
      and treatment of shoulder disorders does not make any difference to the outcome,
      in terms of pain and disability, 1 yr later. Further, there is no advantage to
      injecting steroid in a group with predominant rotator cuff disorder. Trial
      registration. International Standard Randomized Controlled Trial Number 58537244.
      Trial steering committee comprised Prof. Paul Dieppe, Prof. Elaine Hay, Dr Brian
      Hazleman and Dr Kerenza Hood.

PMID- 18820311
TI  - Accuracy of intra-articular injections in peripheral joints performed blindly in
      patients with rheumatoid arthritis.
AB  - OBJECTIVES: To assess the accuracy of blind IA injections (IAIs) in patients with
      RA and determine their effectiveness. METHODS: A controlled prospective study
      including 96 RA patients undergoing blind IAIs in peripheral joints was carried
      out. Clinical evaluation was performed at baseline (T(0)), 1 (T(1)) and 4 (T(4))
      weeks after IAI using the following instruments: visual analogue scale (VAS) for
      pain at rest and movement, VAS for oedema (range 0-10 cm) and morning stiffness.
      Following IAI, radiographic exam was performed in all joints for further analysis
      by two 'blinded' radiologists. The kappa-statistic, chi-square and analysis of
      variance tests were performed to determine potential differences between time
      points of evaluation. Significance level was set as P < 0.05. RESULTS: A total of
      232 injections were performed. Accuracy observed for the shoulder, elbow, wrist,
      MCP joints, knee and ankle were 82, 100, 97, 97, 100 and 77%, respectively. A
      statistically significant improvement was observed for all variables at both T(1)
      and T(4) when compared with T(0). CONCLUSIONS: Blind IAI proved safe and accurate
      when performed by a trained professional. Significant improvement was seen in the
      VAS for pain at rest and during movement, VAS for oedema and morning stiffness.

PMID- 18820312
TI  - Mapping the osteoarthritis knee and hip quality of life (OAKHQOL) instrument to
      the international classification of functioning, disability and health and
      comparison to five health status instruments used in osteoarthritis.
AB  - OBJECTIVES: To map the content of the OsteoArthritis Knee and Hip Quality Of Life
      (OAKHQOL) scale to the International Classification of Functioning, Disability
      and Health (ICF). To compare the OAKHQOL with other instruments used in OA using
      the ICF core set for OA (OA core set). METHODS: We mapped the 43 items of the
      OAKHQOL to ICF categories according to published linking rules. We used the OA
      core set to compare the linked OAKHQOL to available ICF linking results for five
      health status instruments frequently used in OA. RESULTS: The 43 items of the
      OAKHQOL encompass 51 concepts linked to 27 different second-level ICF categories.
      Of the 55 OA core set categories, 20 could be linked to the OAKHQOL. Among the
      body function categories, several items describe sleep, pain and emotional
      function. Only 3 of 19 ICF activity and participation categories are not covered
      by the OAKHQOL. ICF environmental factors explored by the OAKHQOL include several
      important categories: drugs, products for personal use, support and
      relationships. The health status instruments that most comprehensively cover the
      OA core set are the OAKHQOL and the AIMS2-SF. All instruments address pain and
      restrictions in activity and participation but, except for the OAKHQOL and the
      AIMS2-SF, seldom cover emotional and sleep functions, participation in work and
      social life, and environmental factors. CONCLUSION: Compared with other health
      status instruments commonly used in OA, the OAKHQOL covers the highest number of
      OA core set categories and captures specific aspects that are especially valuable
      to patients with knee and hip OA.

PMID- 18820313
TI  - An unusual cause of increased abdominal girth.

PMID- 18820314
TI  - When I use a word ... Ordinary words with extraordinary meanings.

PMID- 18820315
TI  - The patient journey from symptom onset to pacemaker implantation.
AB  - BACKGROUND: Regional variation in permanent pacemaker (PPM) implantation rates is
      well described, the reasons for which are unclear. Significant delays to PPM
      implantation in UK practice were described 20 years ago, but contemporary data
      are lacking. AIM: To investigate delays to PPM implantation and their causes.
      DESIGN: Prospective observational study in a UK regional pacing centre and its
      referring district hospitals. METHODS: A total of 95 consecutive patients
      receiving first PPM implant for bradycardia indications from 1 June 2006 to 31
      August 2006 were included. Hospital records from the referring and implanting
      centres were reviewed to determine the timings of: symptom onset; first hospital
      contact; documented pacing indication (defined by 2002 ACC/AHA/NASPE guidelines);
      referral to implanter; and PPM implantation. RESULTS: Forty-eight patients (51%)
      were referred for pacing urgently; median delay from symptoms to PPM 15 days
      (range 0-7332 days). Forty-seven patients (49%) were referred electively; median
      delay from symptoms to PPM 380 days (range 33-7505 days), P < 0.0001. Twenty
      three of the 47 elective patients (49%) had previous hospitalization with
      symptoms suggestive of bradycardia. Thirty-three of the 95 patients (35%) had a
      Class I or IIa pacing indication which did not trigger a pacing referral.
      CONCLUSION: There are significant delays to PPM implantation in the United
      Kingdom, longer in those treated electively than those managed as emergencies.
      Some delays are due to 'process' problems including waiting lists, but a
      substantial proportion of patients had delays due to failure to refer for pacing
      once a pacing indication was documented.

PMID- 18820316
TI  - Association of mean platelet volume between glucose regulation in children with
      type 1 diabetes.

PMID- 18820317
TI  - Factors related to lower adherence rates to inhaled corticosteroids in children
      and adolescents: a prospective randomized cohort study.
AB  - Asthma morbidity is high, partly due to low adherence to inhaled corticosteroids
      (ICS). This study aims to assess rates and factors related to low adherence to
      ICS over time in asthmatic children and adolescents. METHODS: A concurrent cohort
      study was carried out for 24 months in 168 randomly selected patients suffering
      from persistent moderate asthma. All of them were given beclomethasone
      dipropionate (BDP) free of charge. Adherence rates were verified by pharmacy
      records (doses filled/doses prescribed). A multivariate analysis evaluated
      factors related with low adherence rates. RESULTS: Overall adherence rates were
      72.5, 58.6 and 61.1% in the 4th, 12th and 24th months of follow-up, respectively.
      Factors associated to adherence rates <70% were: mother's schooling level (p =
      0.03), replacement of the caregiver (p = 0.03), prescription greater than two
      puffs/day (p = 0.005), absence of rhinosinusitis (p = 0.002) and age under 7
      years (p = 0.04). Only the number of consultations lower than two in a 4-month
      period was associated to a lower adherence rate in all study periods (p = 0.02).
      CONCLUSIONS: Adherence rates decreased over time, even in patients who had
      received the medication free of charge, and factors related to lower adherence
      changed during the follow-up. Results have shown that adherence had a dynamic
      pattern and its determinants should be re-evaluated continuously. Only the number
      of consultations was associated to a lower adherence rate in all periods,
      pointing out that health programs must recognize and facilitate the access of
      patients needing special care, which can contribute for better adherence and
      reducing asthma morbidity.

PMID- 18820318
TI  - Evaluation of cis-regulatory function in zebrafish.
AB  - As increasing numbers of vertebrate genomes are sequenced, comparative genomics
      offers tremendous promise to unveil mechanisms of transcriptional gene regulation
      on a large scale. However, the challenge of analysing immense amounts of sequence
      data and relating primary sequence to function is daunting. Several teleost
      species occupy crucial niches in the world of comparative genomics, as
      experimental model organisms of wide utility and living roadmaps of molecular
      evolution. Extant species have evolved after a teleost-specific genome
      duplication, and offer the opportunity to examine the evolution of thousands of
      duplicate gene pairs. Transgenesis in zebrafish is being increasingly employed to
      functionally examine non-coding sequences, from fish and mammals. Here, we
      discuss current approaches to the study of gene regulation in teleosts, and the
      promise of future research.

PMID- 18820319
TI  - Socioeconomic status and HIV seroprevalence in Tanzania: a counterintuitive
      relationship.
AB  - OBJECTIVE: To examine the relationship between multiple dimensions of
      socioeconomic status (SES) and HIV seroprevalence in Tanzania. METHODS: Using a
      large nationally representative sample of 7515 sexually active adults drawn from
      the 2003-04 Tanzania HIV/AIDS Indicator Survey, we analysed the relationship
      between multiple SES measures and HIV seroprevalence using weighted logistic
      regression models. RESULTS: In adjusted models, individuals in the highest
      quintile of standard of living had increased odds ratio (OR) of being HIV
      positive (male: OR 2.38, 95% CI 1.17-4.82; female: OR 3.74, 95% CI 2.16-6.49).
      Occupational status was differentially associated with HIV in men and women;
      women in professional jobs had higher OR of being HIV-positive (OR 1.54, 95% CI
      1.02-2.38), whereas unemployed men had higher risk of being HIV-positive (OR
      3.49, 95% CI 1.43-8.58). No marked association was found between increasing
      education and HIV seroprevalence for men (P = 0.83) and women (P = 0.87).
      CONCLUSION: Contrary to the prevailing perception that low SES individuals tend
      to be more vulnerable to HIV-infection, we found a positive association between
      standard of living and HIV-infection. Strategies aimed at reducing HIV-infection
      needs to be cognizant of the complex social heterogeneity in the patterns of HIV
      infection.

PMID- 18820320
TI  - Ethnic variability in adiposity and cardiovascular risk: the variable disease
      selection hypothesis.
AB  - Evidence increasingly suggests that ethnic differences in cardiovascular risk are
      partly mediated by adipose tissue biology, which refers to the regional
      distribution of adipose tissue and its differential metabolic activity. This
      paper proposes a novel evolutionary hypothesis for ethnic genetic variability in
      adipose tissue biology. Whereas medical interest focuses on the harmful effect of
      excess fat, the value of adipose tissue is greatest during chronic energy
      insufficiency. Following Neel's influential paper on the thrifty genotype,
      proposed to have been favoured by exposure to cycles of feast and famine, much
      effort has been devoted to searching for genetic markers of 'thrifty metabolism'.
      However, whether famine-induced starvation was the primary selective pressure on
      adipose tissue biology has been questioned, while the notion that fat primarily
      represents a buffer against starvation appears inconsistent with historical
      records of mortality during famines. This paper reviews evidence for the role
      played by adipose tissue in immune function and proposes that adipose tissue
      biology responds to selective pressures acting through infectious disease.
      Different diseases activate the immune system in different ways and induce
      different metabolic costs. It is hypothesized that exposure to different
      infectious disease burdens has favoured ethnic genetic variability in the
      anatomical location of, and metabolic profile of, adipose tissue depots.

PMID- 18820321
TI  - Open-heart surgery at school age does not affect neurocognitive functioning.
AB  - AIMS: Although neurocognitive problems after open-heart surgery for congenital
      heart disease are frequent, due to a shortage of prospective studies assessing
      neurocognitive functioning both before and after the procedure, the exact nature
      of the deficits usually remains unknown. The present study aims at assessing the
      neurocognitive effects of, in particular, cardiopulmonary bypass at school age.
      In addition, surgery-related risk factors for reduced neurocognitive outcome are
      explored. METHODS AND RESULTS: Participants were aged between 6 and 16 years.
      Forty-three children indicated for open-heart surgery and a comparison group of
      19 children scheduled for interventional cardiac catheterization completed a
      neurocognitive assessment battery before and 1 year after their procedures. Forty
      healthy matched controls did so at a 1 year interval. The baseline-to-follow-up
      outcomes were similar in all three groups. The observed improvements most likely
      resulted from increased age and the repeated neurocognitive assessment. No risk
      factors for postsurgical neurocognitive deficits were identified. CONCLUSION: The
      present study demonstrates that at school age cardiac surgery using full-flow
      cardiopulmonary bypass does not affect neurocognitive functioning.

PMID- 18820322
TI  - Differential diagnosis of suspected apical ballooning syndrome using contrast
      enhanced magnetic resonance imaging.
AB  - AIMS: The apical ballooning syndrome (ABS) is a new diagnostic entity which is
      increasingly recognized. Precise magnetic resonance imaging (MRI) data are not
      yet available and there is little evidence for the differential diagnosis of ABS
      assessed by MRI. METHODS AND RESULTS: Between January 2005 and January 2008, 6100
      consecutive patients with diagnosis of acute coronary syndrome underwent left
      heart catheterization. In 59 patients (1.0%), coronary angiography revealed
      normal coronary arteries, but left ventriculography showed left ventricular
      dysfunction with apical ballooning. These 59 patients underwent cardiac MRI using
      a 1.5 T MRI scanner. In 13 patients (22.0%), MRI revealed diagnosis of myocardial
      infarction, in eight patients (13.6%) diagnosis of myocarditis. In all other 38
      (64.4%) patients (36 female, age 73 +/- 10 years) with suspected ABS, no delayed
      enhancement or signs of inflammation were detected. Follow-up MRI after 3 months
      showed a completely normalized left ventricular ejection in all patients with
      suspected ABS. Similarly, the end-diastolic volume and end-systolic volume
      improved at follow-up. CONCLUSION: Cardiac MRI allows differentiating ABS from
      other rare causes with unobstructed coronary vessels such as myocarditis and
      coronary emboli with spontaneous lysis. Therefore, cardiac MRI can add valuable
      information in all patients with suspected ABS for further differential
      diagnosis.

PMID- 18820323
TI  - Septal branch aneurysm during coronary computed tomography angiography: a cause
      of right bundle branch block?

PMID- 18820324
TI  - Heart rate and mortality from cardiovascular causes: a 12 year follow-up study of
      379,843 men and women aged 40-45 years.
AB  - AIM: To study the relationship between heart rate and (a) all deaths and (b)
      cardiovascular deaths in a large cohort of middle-aged Norwegian men and women.
      METHODS AND RESULTS: A prospective study of participants in cardiovascular
      surveys that were carried out in 1985-1999 and covered men and women aged 40-45
      years in all counties except the capital, Oslo. In total, 180,353 men and 199,490
      women aged 40-45 years without cardiovascular history or diabetes accrued 4 775
      683 years of follow-up. There was a positive and graded association between heart
      rate and mortality from all causes, as well as between heart rate and deaths from
      cardiovascular disease (CVD), ischaemic heart disease, and stroke. However, these
      associations were greatly reduced when we adjusted for the main risk factors of
      disease. The hazard ratios for any death were reduced from 3.14 to 1.82 for men
      (95% CI, 1.62-2.04) and from 2.14 to 1.37 for women (95% CI, 1.19-1.59), when we
      compared > or =95 b.p.m. with <65 b.p.m. The corresponding figures for CVD were a
      reduction from 4.79 to 1.51 for men (95% CI, 1.21-1.87) and from 2.68 to 0.78 for
      women (95% CI, 0.53-1.15). CONCLUSION: In this cohort of middle-aged men and
      women, a crude association between heart rate and death from CVDs was greatly
      weakened when we adjusted for the main risk factors of disease. This suggests
      that an increased heart rate in middle age may be a marker of high cardiovascular
      risk, but is not an independent risk factor.

PMID- 18820325
TI  - Opinions of veterinarians about the age at which kittens should be neutered.
AB  - The mean age recommended by veterinary practices for neutering kittens is 22.6
      weeks, with only 28 per cent of veterinarians considering it appropriate to
      neuter 12- to 16-week-old kittens. Multivariable logistic regression was used to
      identify variables associated with veterinarians' opinion that 12 to 16 weeks is
      an appropriate age at which to neuter kittens. Significant risk factors included
      time since graduation, perception of the problem of there being too many unwanted
      domestic cats and their practice's policy on the recommended neutering age.
      Veterinarians who thought that neutering eight- to 11-week-old rescue kittens
      before homing was justified and veterinarians who had neutered 12- to 16-week-old
      domestic kittens within the previous year were more likely to consider that
      neutering 12- to 16-week-old kittens was appropriate. Veterinarians who thought
      that surgical complications, anaesthetic complications and lower urinary tract
      disease were, or might be, more likely to occur in kittens neutered at 12 to 16
      weeks than in those neutered at six months of age, were significantly less likely
      to think that neutering 12- to 16-week-old kittens was appropriate.

PMID- 18820326
TI  - Factors affecting the mortality of pigs being transported to slaughter.
AB  - A multilevel logistic regression model was used to identify and quantify the
      effects of factors affecting the mortality of pigs being transported to slaughter
      under commercial conditions. A survey of 739 journeys to 37 slaughterhouses in
      five eu countries was carried out, and information potentially related to the
      welfare and mortality of the pigs and the number of injuries were recorded. The
      average temperature during the journey, its duration, the average loading time
      per pig, the recorded injuries, fasting before transport, and the interaction
      between fasting and journey duration were used in the final model. The average
      mortality was 0.11 per cent and the average proportion of injured pigs was 0.36
      per cent, and these figures were significantly correlated (P<0.001). In 29 per
      cent of the journeys the pigs were not fasted before being loaded, which doubled
      the risk of mortality irrespective of whether the pigs were injured or not. The
      risk of mortality increased with average temperature. In journeys with fasted
      pigs that did not have any recorded injury, average temperature was more
      important than the duration of the journey. The risk of mortality increased as
      the average time taken to load them decreased, and the risk was highest when the
      pigs were not fasted and when injuries were recorded. Other factors such as the
      country, loading density, availability of drinking water and type of ventilation
      did not affect the risk of mortality.

PMID- 18820327
TI  - Sarcina-like bacteria associated with bloat in young lambs and calves.
AB  - Sarcina species are fastidious Gram-positive anaerobic bacteria that occur in
      cubical packets of eight or more cells. In 2006 to 2007, they were associated
      with cases of acute abomasal bloat in young lambs and calves. Two incidents were
      in lambs aged three to six weeks that were found dead, with one or two cases in
      each of a group of 15 and 100 lambs. Three incidents were recorded in small
      groups of calves up to 10 days of age, two cases in each incident, with the
      calves found dead or dying after a short illness characterised by bloat. Their
      gross lesions included emphysema and oedema of the abomasal wall, mucosal
      hyperaemia and haemorrhage, and rupture of the abomasum. Histological lesions
      included abomasitis with congestion, haemorrhage, emphysema and oedema. Bacteria
      characteristic of Sarcina species were observed in sections associated with the
      superficial mucosa of these cases, but the bacteria were not detected in
      cultures.

PMID- 18820328
TI  - Toxocara species egg contamination of soil from children's play areas in southern
      England.

PMID- 18820329
TI  - Clinical evaluation of alfaxalone in cyclodextrin for the induction of
      anaesthesia in rabbits.

PMID- 18820330
TI  - Suspected mitochondrial myopathy in a springer spaniel.

PMID- 18820331
TI  - Bluetongue control strategy.

PMID- 18820332
TI  - Cystic fibrosis and the isolation of Pseudomonas aeruginosa from horses.

PMID- 18820333
TI  - Control of TB in cattle and badgers.

PMID- 18820334
TI  - Bluetongue control strategy.

PMID- 18820335
TI  - Bluetongue control strategy.

PMID- 18820336
TI  - Testing for the CEMO, Klebsiella pneumoniae and Pseudomonas aeruginosa.

PMID- 18820337
TI  - Beneficial side effects?

PMID- 18820338
TI  - Nitrite reductase activity of cytochrome c.
AB  - Small increases in physiological nitrite concentrations have now been shown to
      mediate a number of biological responses, including hypoxic vasodilation,
      cytoprotection after ischemia/reperfusion, and regulation of gene and protein
      expression. Thus, while nitrite was until recently believed to be biologically
      inert, it is now recognized as a potentially important hypoxic signaling molecule
      and therapeutic agent. Nitrite mediates signaling through its reduction to nitric
      oxide, via reactions with several heme-containing proteins. In this report, we
      show for the first time that the mitochondrial electron carrier cytochrome c can
      also effectively reduce nitrite to NO. This nitrite reductase activity is highly
      regulated as it is dependent on pentacoordination of the heme iron in the protein
      and occurs under anoxic and acidic conditions. Further, we demonstrate that in
      the presence of nitrite, pentacoordinate cytochrome c generates bioavailable NO
      that is able to inhibit mitochondrial respiration. These data suggest an
      additional role for cytochrome c as a nitrite reductase that may play an
      important role in regulating mitochondrial function and contributing to hypoxic,
      redox, and apoptotic signaling within the cell.

PMID- 18820340
TI  - Participant experiences in a workplace pedometer-based physical activity program.
AB  - BACKGROUND: Limited process evaluation of pedometer-based interventions has been
      reported. METHODS: Feedback via focus groups (n=38) and exit questionnaires
      (n=68) was used to examine participants' experiences in a group-based, pedometer
      based physical activity (PA) program delivered in the workplace. RESULTS: The
      pedometer was described as a useful tool for increasing awareness of PA,
      providing motivation and visual feedback, and encouraging conversation and
      support among participants and others such as family and friends. Group meetings
      provided motivation and social support, as did participation by coworkers. Self
      selected goals, self-selected PA strategies, and recording of steps/d were also
      important. CONCLUSIONS: Given the importance of social support as a mediating
      variable in changing PA behavior, future pedometer-based programs might benefit
      from including a group-based component.

PMID- 18820341
TI  - Walking behaviors reported in the American Time Use Survey 2003-2005.
AB  - BACKGROUND: We report walking for shopping, exercise, transportation, and walking
      the dog, among other sources captured in the 2003 to 2005 American Time Use
      Survey (ATUS). METHODS: We extracted and analyzed 8 walking behaviors (by sex,
      age, education level, and race/ethnicity) from 24 hours of activities recalled by
      telephone interview for 15,175 males and 19,518 females age<15 years. RESULTS: On
      any given day in 2003 to 2005, 45.8% of Americans participated in a median of 45
      minutes of any walking activities; 31.6% walked for shopping purposes, 12.5%
      walked for transportation, 4.8% walked for exercise, and 2.5% walked the dog.
      College-educated respondents more commonly reported walking while shopping,
      walking for exercise, and dog walking. Those with less than a high school
      education more commonly reported walking for transportation. CONCLUSIONS: Despite
      limitations identified in imputing explicit and implicit performance of walking
      behaviors in the ATUS, Americans engage in a wide variety of walking behaviors
      that are not well represented by surveys focused only on leisure-time behaviors.
      Public health implications include increased availability of multiple and varied
      opportunities for walking, especially through environmental shifts toward more
      walkable places and destinations and policy shifts that support walking behaviors
      over competing transportation modes.

PMID- 18820342
TI  - Real-world evaluation of a community-based pedometer intervention.
AB  - BACKGROUND: We evaluated a pedometer-based community intervention under real
      world conditions. METHODS: Participants (n=559) provided demographic and health
      information using surveys and steps/d at baseline and during the last week the
      participants were in the program. A 1-year follow-up was conducted, but in
      keeping with real-world conditions, no incentives were offered to participate.
      RESULTS: Participants (89% female, age 48.1 [SD=12] years) took 7864 (3114)
      steps/d at baseline. Postprogram voluntary response rates to mailed surveys were
      41.3% at 12 weeks and 22.8% at 1 year. Program completers reported significantly
      higher steps/d at 12 weeks (approximately 12,000 steps/d) and 1 year
      (approximately 11,000 steps/d) compared with baseline. CONCLUSIONS: The
      improvement in steps/d in this real-world implementation was consistent with more
      controlled studies of pedometer-based interventions. Low response to voluntary
      follow-up is a study limitation but is expected of real-world evaluations.

PMID- 18820343
TI  - Are current body mass index referenced pedometer step-count recommendations
      applicable to US youth?
AB  - BACKGROUND: The purpose of this study was to cross-validate international BMI
      referenced steps/d cut points for US girls (12,000 steps/d) and boys (15,000
      steps/d) 6 to 12 years of age. METHODS: Secondary pedometer-determined physical
      activity data from US children (N=1067; 633 girls and 434 boys, 6 to 12 years)
      were analyzed. Using international BMI classifications, cross-validation of the
      12,000 and 15,000 steps/d cut points was examined by the classification
      precision, sensitivity, and specificity for each age-sex stratum. RESULTS: For
      girls (boys) 6 to 12 years, the 12,000 (15,000) steps/d cut points correctly
      classified 42% to 60% (38% to 67%) as meeting (achieved steps/d cut point and
      healthy weight) and failing (did not achieve steps/d cut point and overweight).
      Sensitivity ranged from 55% to 85% (64% to 100%); specificity ranged from 23% to
      62% (19% to 50%). CONCLUSION: The utility of pedometer steps/d cut points was
      minimal in this sample given their inability to differentiate among children who
      failed to achieve the recommended steps/d and exhibited an unhealthy weight.
      Caution, therefore, should be used in applying previous steps/d cut points to US
      children.

PMID- 18820344
TI  - Factors associated with exercise counseling and program preferences among breast
      cancer survivors.
AB  - OBJECTIVE: Our aim was to assess differences in exercise counseling preferences,
      program preferences, and telephone/Internet access among breast cancer survivors
      based on exercise behavior and demographic, medical, social cognitive, and
      environmental factors. METHODS: A self-administered survey was returned by 192
      breast cancer survivors. RESULTS: Participants were Caucasian (98%), and the mean
      age was 64+/-11.5 years. Participants preferring an exercise specialist were more
      likely to report current treatment, higher self-efficacy, greater perceived
      barriers, and a residential environment conducive to physical activity.
      Participants preferring face-to-face counseling and exercising outdoors were
      younger, and those preferring to exercise alone and at home reported lower social
      support. Low-intensity exercise was preferred by participants who were sedentary,
      obese, less self-efficacious, enjoyed exercise less, perceived greater barriers,
      and reported lower social support. Participants with Internet access were more
      apt to be younger with higher income and greater social support. CONCLUSIONS:
      Demographic, medical, social cognitive, and environmental factors might influence
      exercise preferences and Internet access. Future research assessing the
      effectiveness of tailoring interventions based on these factors is warranted.

PMID- 18820345
TI  - Effects of self-efficacy, body mass, and cardiorespiratory fitness on exercise
      motives in Chinese college students.
AB  - BACKGROUND: Researchers have studied exercise determinants primarily from
      cognitive and social psychology perspectives, which typically give minimal
      attention to the body as a physical and biological entity. With the belief that
      tapping into multidimensional variables would potentially help us better
      understand motivation in exercise, we designed this study to examine the
      influences of self-efficacy, body mass, and cardiorespiratory fitness level on
      Chinese college students' leisure-time exercise motives. METHODS: 208 college
      students completed measures of self-efficacy and exercise motives during regular
      physical education classes. Their body mass and cardiorespiratory fitness level
      data were derived from the latest annual physical training test. Multiple
      regression analyses were conducted to investigate the effects of self-efficacy,
      body mass, and cardiorespiratory fitness on exercise motives. RESULTS:
      Cardiorespiratory fitness level and self-efficacy in exercise significantly
      contributed to both psychological and interpersonal motives. Body mass was the
      only significant predictor for body-related motives. However, analyses of health
      and fitness motives did not result in any significant predictors. CONCLUSION:
      Physical and psychological variables have both independent and specialized
      functions on exercise motives. Future motivational studies in exercise should pay
      greater attention to ecological approaches that account for physical,
      psychological, and social factors.

PMID- 18820346
TI  - School design and physical activity among middle school girls.
AB  - Building design and grounds might contribute to physical activity, and youth
      spend much of their daylight hours at school. We examined the associations among
      school building footprints, the size of school grounds, and in-school physical
      activity of 1566 sixth-grade girls from medium to large middle schools enrolled
      in the Trial of Activity for Adolescent Girls (TAAG). The school building
      footprint and the number of active outdoor amenities were associated with
      physical activity among adolescent girls. On average, the school footprint size
      accounted for 4% of all light physical activity and 16% of all MET-weight
      moderate-to-vigorous physical activity (MW-MVPA) during school hours. Active
      outdoor amenities accounted for 29% of all MW-MVPA during school. School design
      appears to be associated with physical activity, but it is likely that
      programming (eg, physical education, intramurals, club sports), social factors,
      and school siting are more important determinants of total physical activity.

PMID- 18820347
TI  - Does physical activity affect the predictive value of health-related fitness
      tests on walking difficulty?
AB  - BACKGROUND: Low levels of physical activity (PA) and poor fitness tend to predict
      a decline in mobility. The current study investigated whether PA modifies the
      predictive value of health-related fitness (HRF) tests on difficulty in walking 2
      km (WD). METHODS: PA was assessed by self-reported questionnaires in 1990 and
      1996. Subjects age 55 to 69 years and free of self-reported WD participated in
      assessment of HRF in 1996. Occurrence of WD was assessed by questionnaire in 2002
      (n=537). RESULTS: There were no statistically significant interactions between PA
      and HRF tests; thus, PA and HRF were both independent predictors of WD.
      Regardless of the PA level, the subjects in the poorest performing third in each
      HRF test had higher risk of WD than the subjects in the best performing third.
      CONCLUSIONS: PA and HRF seemed to be independent predictors of WD, although the
      association of PA with WD was weaker than the association of HRF. Thus, PA did
      not modify the predictive value of HRF on WD.

PMID- 18820348
TI  - Validation of the International Physical Activity Questionnaire-Short among
      Blacks.
AB  - BACKGROUND: The International Physical Activity Questionnaire-Short Form (IPAQ-S)
      has been evaluated against accelerometer-determined physical activity measures in
      small homogenous samples of adults in the United States. There is limited
      information about the validity of the IPAQ-S in diverse US samples. METHODS: 142
      Blacks residing in low-income housing completed the IPAQ-S and wore an
      accelerometer for up to 6 days. Both 1- and 10-minute accelerometer bouts were
      used to define time spent in light, moderate, and vigorous physical activity.
      RESULTS: We found fair agreement between the IPAQ-S and accelerometer-determined
      physical activity (r=.26 for 10-minute bout, r=.36 for 1-minute bout).
      Correlations were higher among men than women. When we classified participants as
      meeting physical activity recommendations, agreement was low (kappa=.04, 10
      minute; kappa=.21, 1-minute); only 25% of individuals were classified the same by
      both instruments (10-minute bout). CONCLUSIONS: In one of the few studies to
      assess the validity of a self-reported physical activity measure among Blacks, we
      found moderate correlations with accelerometer data, though correlations were
      weaker for women. Correlations were smaller when IPAQ-S data were compared using
      a 10- versus a 1-minute bout definition. There was limited evidence for agreement
      between the instruments when classifying participants as meeting physical
      activity recommendations.

PMID- 18820349
TI  - Malaria in the South-East Asia region: myth & the reality.

PMID- 18820350
TI  - Natural reservoir, zoonotic tuberculosis & interface with human tuberculosis: an
      unsolved question.

PMID- 18820351
TI  - Changing epidemiology of hepatitis A infection.

PMID- 18820352
TI  - PKDL--a drug related phenomenon?

PMID- 18820353
TI  - Targeting protein acetylation for improving cancer therapy.
AB  - Acetylation is one of the most important post-translational modification of
      proteins determining the structure, function and intracellular localization that
      plays an important role in the signal transduction pathways related to diverse
      cell functions, both during unstimulated and stress conditions. Protein
      acetylation in cells is regulated by a co-ordinated action of histone acetyl
      transferases (HAT) and histone deacetylases(HDAC) that ensures the maintenance of
      homeostasis and execution of activities related to damage response viz. DNA
      repair, cell cycle delay, apoptosis and senescence. Since inhibition of histone
      deacetylation, stalls the progress of many nuclear events including proliferation
      and damage response events on the one hand and the levels of deacetylases are
      elevated in many tumours on the other. Histone deacetylase has been among the
      targets for the development of anticancer drugs and adjuvant. The recent
      observation showing acetylation of proteins by calreticulin (an endoplasmic
      reticulum resident protein) with a high efficiency when polyphenolic acetates are
      the acetyl group donating molecules and acetyl CoA as weak substrate extends the
      realm of protein acetylation beyond HAT/HDAC combination. Elucidation of the
      relative roles of HAT/HDAC mediated acetylation viz. a calreticulin mediated
      acetylation in cell function under a variety of stress conditions would hold key
      to the design of drugs targeting protein acetylation system.

PMID- 18820354
TI  - Biological control of mosquito populations through frogs: opportunities &
      constrains.
AB  - The use of frogs and tadpoles for disease vector control is still largely
      unexplored. Frogs are an important part of the ecosystem with a role for insect
      and pest control including mosquitoes. Available information suggests the
      existence of many direct and indirect factors affecting the growth and survival
      of both prey and predators. Other controphic species that have influence on this
      relationship also show considerable effect. Still, the associations of different
      prey and predator relationships in the environment to assess the feasibility of
      use of a species as biocontrol agent for vector control and management. However,
      frogs cannot be used as an independent intervention for disease vector control
      and more research is needed to use them effectively for mosquito control.

PMID- 18820355
TI  - Isolation of Mycobacterium bovis & M. tuberculosis from cattle of some farms in
      north India--possible relevance in human health.
AB  - BACKGROUND & OBJECTIVE: Infection due to Mycobacterium bovis typically occurs in
      cattle and animals transmit infection to each other. The choice of appropriate
      clinical specimen is very important for isolation of M. bovis and M. tuberculosis
      from cattle. The present study reports the isolation of M. tuberculosis and M.
      bovis from different types of specimens from cattle suspected to be suffering
      from tuberculosis in certain organized cattle farms in north India. METHODS: A
      total of 768 specimens (heparinized or EDTA containing blood (162), fine needle
      aspirates from prescapular lymph gland (PSLG,160), milk (154), pharyngeal swab
      (PhS, 98), rectal pinch (RP, 97) and faecal sample (97) from 161 cattle of
      organized cattle farms in north India suspected to be suffering from tuberculosis
      were analyzed. After decontamination by modified Petroff's method isolation of
      M.tuberculosis complex was done on Lowenstein-Jensen medium (with and without
      pyruvate). The culture isolates were identified as M. tuberculosis and M. bovis
      on the basis of biochemical tests. RESULTS: A total of 54 M. tuberculosis complex
      isolates were obtained, of them 40 were identified as M.bovis and 14 as M.
      tuberculosis. M.bovis were isolated from 12 of 38 animals in group A (Tuberculin
      +ve with signs of tuberculosis), 7 of 37 animals in group B (Tuberculin +ve and
      apparently healthy), 9 of 21 group C animals in (Tuberculin -ve with clinical
      signs of tuberculosis), 4 of 26 animals in group D (Tuberculin -ve and apparently
      healthy), 4 of 27 group E animals (having non-mycobacterial infection) and 4 of
      12 animals in group F (having clinical signs such as debilitated condition,
      cough, decreasing milk production, etc). Maximum number of M. bovis (19/40,
      47.5%) and M. tuberculosis (5/14, 35.7%) isolates were grown from prescapular
      lymph gland biopsy (PSLG) followed by blood from which 9/40 (22.5%) M. bovis and
      4/14 (28.5%) M. tuberculosis were isolated. M. bovis [6/40(15%)] and M.
      tuberculosis [4/14(28.5%)] were also isolated from milk. Only 3/40 (7.5%)
      isolates of M.bovis could be isolated from 97 rectal pinch followed by 98
      pharyngeal swab 2/40 (5%) and 97 fecal samples 1/40 (2.5%) while 1/14 (7.1%)
      M.tuberculosis isolates were obtained from pharyngeal swab. INTERPRETATION &
      CONCLUSION: Among the samples analyzed, PSLG was found to be most suitable
      specimen for isolation of M. tuberculosis complex from cattle and is thus of
      diagnostic importance. M. bovis in milk indicates the need to investigate the
      transmission to human in such settings. Isolation of M. bovis and/or M.
      tuberculosis from apparently healthy cattle indicates sub-clinical infection in
      the herd. Further, isolation of a significant number of M. tuberculosis from
      cattle suggests possible human-to-cattle transmission which need to be confirmed
      by prospective studies including tools like DNA fingerprinting.

PMID- 18820356
TI  - Investigation of a hepatitis A outbreak in children in an urban slum in Vellore,
      Tamil Nadu, using geographic information systems.
AB  - BACKGROUND & OBJECTIVE: An outbreak of symptomatic viral hepatitis in children
      less than 10 yr of age in Vellore, south India, was investigated and the disease
      pattern studied using serological and epidemiological methods, supplemented by
      geographic information systems (GIS) mapping. METHODS: Three cases of hepatitis A
      were identified during routine surveillance in a birth cohort House-to-house
      visits were undertaken to identify other symptomatic cases and samples collected
      for anti- HAV IgM, ELISA testing. All cases and controls were mapped and geo
      referenced using Arc View GIS 3.3. Spatial clustering was investigated using
      SaTScan 7.0.1 software. Drinking water sources were tested for coliform counts
      with the most probable number technique. RESULTS: Of the 965 children surveyed,
      26 (2.78%) had jaundice between February to July 2006. From the 26 patients, 11
      (42.3%) blood samples were obtained and tested for anti-HAV IgM; 10 (90.9%) were
      found to be positive. Water analysis showed high coliform counts in all samples.
      No spatial clustering of cases could be detected. INTERPRETATION & CONCLUSION:
      The outbreak was identified because of the symptomatic presentation of the cases.
      Our study highlighted the increasing detection of symptomatic children with
      hepatitis A virus infection. Water sources in the area were contaminated and may
      have served as the source of infection. The lack of clustering in GIS analysis
      could be due to the common water source.

PMID- 18820357
TI  - Impact of amphotericin-B in the treatment of kala-azar on the incidence of PKDL
      in Bihar, India.
AB  - BACKGROUND & OBJECTIVE: Of the two reservoirs of infection of kala-azar i.e.,
      patients of kala-azar and post kala-azar dermal leishmaniasis (PKDL), PKDL
      provides easy access for the sandfly to pick up the parasites. In the last
      epidemic of 1977 in India, the importance of PKDL as a potential cause of
      increase in number of kala-azar cases was ignored. During recent years, we found
      an increase in the cases of kalaazar whereas cases of PKDL were decreasing in
      Bihar. We undertook this study to find out reasons for this phenomenon. METHODS:
      These three different settings were selected to study the trends of the disease.
      (i) Cases of PKDL registered in the Dermatology Department of Patna Medical
      College Hospital (PMCH), one of the largest and oldest teaching hospital in
      Bihar, between 1970 and 2005; (ii) Rajendra Memorial Research Institute of
      Medical Sciences, Patna (RMRIMS), a research institute exclusively devoted to
      kala-azar (2000 and 2005); and (iii) interviews with two leading dermatologists
      of Patna selected by lottery on the incidence of PKDL and possible causes of its
      decrease, if any. The number of cases of kala-azar (visceral leishmaniasis, VL)
      from Bihar was studied from Malaria Departments of the Government of Bihar and
      Government of India, the two nodal departments dealing with the kala-azar.
      RESULTS: Analysis of data from Dermatology Department of PMCH showed increase in
      number of cases of PKDL from two in 1970 to 12 in 1976, a year before the first
      epidemic of kala-azar in 1977 with 100,000 cases. Kala-azar cases decreased to
      11,120 in 1982 due to control measures taken between 1977- 1979 but cases of PKDL
      reached 28 and kept on increasing. During 1950 to 1977, low dose and short
      duration regimen of sodium antimony gluconate (SAG) was mainly used in the
      treatment of kala-azar. Between 1977-1991 increasing incidence of
      unresponsiveness to SAG, led to the usage of longer duration and higher dose
      regimen of SAG, more use of amphotericin B (AMB) for SAG resistant cases and also
      as a first line drug for kala-azar and PKDL. The number of kala-azar cases
      started decreasing after control measures taken during 1992-1994 but cases of
      PKDL continued decreasing. The effect of control measures on the incidence of
      kala-azar was visible upto 2002, but decrease in number of PKDL cases continued.
      In 2005 the number of PKDL cases was 14 but number of kala-azar cases reached
      21,177 in Bihar. In the interview, the two dermatologists also opined that PKDL
      was decreasing due to increased use of amphotericin B in the treatment of kala
      azar. Trend analysis done on the data of PMCH and RMRIMS showed that PKDL will
      decrease in coming years and kala-azar will increase. INTERPRETATION &
      CONCLUSION: Incidence of PKDL decreased in PMCH and RMRIMS and also suggested by
      two dermatologists that extensive use of amphotericin B in the treatment of kala
      azar might be responsible for decrease in number of cases of PKDL.

PMID- 18820358
TI  - Detection & management of anaemia in pregnancy in an urban primary health care
      institution.
AB  - BACKGROUND & OBJECTIVE: In India, anaemia in pregnancy remains a major public
      health problem associated with increased risk of low birth weight deliveries. A
      study was carried out at an urban primary health institution in Delhi, to assess
      feasibility of screening all pregnant women attending antenatal clinic for
      anaemia, identifying those with moderate anaemia (haemoglobin between 5.0 - 7.9
      g/dl), administering intramuscular (im) therapy to them in the out-patient
      department (OPD), and observing the impact on maternal haemoglobin (Hb) levels
      and birth weight of the infant. METHODS: In the antenatal clinic all pregnant
      women were screened for anaemia. Women with Hb between 5.0- 7.9 g/dl were
      counselled and those who were willing, were given six intramuscular injections
      each consisting of iron sorbitol citric acid complex containing 150 microg
      elemental iron, 1500 microg folic acid, 150 microg hydroxocobalamine acetate
      (vitamin B1)). They were followed up through pregnancy and till delivery. Birth
      weight of infants of women who received therapy were compared with birth weight
      of infants born in DCMC. RESULTS: Over 80 per cent of 3698 women who attended the
      antenatal clinic were anaemic; 745 (20.1%) had Hb between 5.0-7.9 g/dl. Of these,
      419 women agreed to take im therapy as outpatients; 367 took all 6 injections.
      Metallic taste on the tongue, nausea, vomiting and pain at the injection site
      were the side effects reported. The mean Hb even 9 wk after completion of therapy
      was only 9.6 g/dl. Mean birth weight in 340 women who completed the treatment was
      2.8 kg - significantly (P<0.001) higher than birth weight in women who had Hb
      <8.0 g/dl at the time of delivery, but lower than birth weight of infants born to
      non anaemic women. INTERPRETATION & CONCLUSION: In urban primary health care
      institutions, it is possible to screen pregnant women for anaemia, identify those
      with Hb between 5.0 and 7.9 g/dl and give them im therapy as outpatients. Use of
      a preparation with fewer and milder side effects, counselling and support of
      women who develop side effect may result in high compliance rates; 900 mg of
      elemental iron as iron sorbitol citric acid was insufficient to raise mean Hb
      beyond 9.6 g/dl. The dosage has to be increased to achieve optimal results in
      relation to maternal haemoglobin levels and birth weight.

PMID- 18820359
TI  - Detection & molecular confirmation of a focus of Plasmodium malariae in Arunachal
      Pradesh, India.
AB  - BACKGROUND & OBJECTIVE: During a malaria epidemiological study in Arunachal
      Pradesh, Plasmodium malariae like human malaria parasites were seen in blood
      smears from fever cases. The study was undertaken to detect the presence of P.
      malariae and to confirm its identity through DNA based polymerase chain reaction
      approach. METHODS: Fever survey was carried out in 22 villages in Indo-Myanmar
      bordering district of Lohit, Arunachal Pradesh in 2005. Morphologically suspected
      P. malariae cases were confirmed using nested PCR based on 18S small subunit
      ribosomal DNA gene sequence. RESULTS: Screening of 1,995 fever cases resulted in
      9 probable cases of P. malariae based on morphological identification in Chakma
      tribe people residing in 2 villages. Nested PCR confirmed the identity of all
      probable cases of P. malariae by producing diagnostic band of 144 bp. PCR method
      was able to detect mixed infection of P. malariae with P. vivax and with P.
      falciparum. INTERPRETATION & CONCLUSION: P. malariae may have been present in
      Arunachal Pradesh but most probably is being misdiagnosed due to its close
      resemblance with P. vivax, especially in ring forms. Estimation of actual case
      load of P. malariae in north-east India is, therefore, important with accurate
      species identification using molecular methods.

PMID- 18820360
TI  - Incidence of Haemophilus influenzae type b meningitis in India.
AB  - BACKGROUND & OBJECTIVE: Vaccine policy depends on locally relevant disease burden
      estimates. The incidence of Haemophilus influenzae type b (Hib) disease is not
      well characterized in the South Asian region, home to 30 per cent of the world's
      children. There are limited data from prospective population incidence studies of
      Hib in Asia, and no data available from India. We therefore carried out this
      study to assess the burden of Hib meningitis in India. METHODS: A prospective
      surveillance study was carried out during 1997 and 1999 in hospitals for cases of
      Hib meningitis from 5 administrative areas of an Indian district (Vellore, Tamil
      Nadu) with 56,153 children under 5 yr of age, over a 24 month period RESULTS:
      Ninety seven cases of possible meningitis (> 10 WBC/microl in CSF) were reported,
      an annual incidence of 86 per 100,000 (95%CI 69 to 109) in 0-4 yr old children,
      and 357 per 100,000 in 0-11 month infants. Eighteen had proven bacterial
      meningitis, an annual incidence of 15.9 per 100,000. Eight CSF had Hib by culture
      or antigen testing, an annual incidence of 7.1 per 100,000 (95%CI 3.1 to 14.0) in
      children 0-59 months. In infants 0-11 months of age, the incidence of Hib
      meningitis was 32 per 100,000 (95%CI 16 to 67) and in the 0-23 month group it was
      19 (95%CI 8 to 37). INTERPRETATION & CONCLUSION: Our data are the first minimal
      estimate of the incidence of Hib meningitis for Indian children. The observed
      incidence data are similar to European reports before Hib vaccine use, suggest
      substantial disease before 24 months of age, and provide data useful for policy
      regarding Hib immunization.

PMID- 18820361
TI  - Antifilarial activity of Caesalpinia bonducella against experimental filarial
      infections.
AB  - BACKGROUND & OBJECTIVE: Lymphatic filariasis is a disabling disease that
      continues to cripple population in tropical countries. Currently available
      antifilarial drugs are not able to control the disease. Therefore, a better
      antifilarial is urgently required for proper management of the disease. We
      undertook this study to assess the antifilarial activity of Caesalpinia
      bonducella-seed kernel against rodent filarial parasite in experimental model.
      METHODS: Microfilaraemic cotton rats and Mastomys coucha harbouring Litomosoides
      sigmodontis and Brugia malayi respectively, were treated with crude extract or
      fractions of the seed kernel C. bonducella through oral route for 5 consecutive
      days. Microfilaricidal, macrofilaricidal and female worm sterilizing efficacy was
      assessed. RESULTS: Crude extract showed gradual fall in microfilariae (mf) count
      in L. sigmodontis-cotton rat model from day 8 post-treatment attaining more than
      95 per cent fall by the end of observation period. It also exhibited 96 per cent
      macrofilaricidal and 100 per cent female sterilizing efficacy. The butanol
      fraction F018 caused 73.7 per cent reduction in mf count and 82.5 per cent
      mortality in adult worms with 100 per cent female sterilization. The aqueous
      fraction F019 exerted more than 90 per cent microfilaricidal activity and 100 per
      cent worm sterilization. Two chromatographic fractions, F024 and F025 of hexane
      soluble fraction exhibited 64 and 95 per cent macrofilaricidal activity,
      respectively. Both the fractions caused gradual fall in microfilaraemia and 100
      per cent worm sterilization. In B. malayi-M. coucha model F025 showed gradual
      reduction in microfilaraemia and caused 80 per cent sterilization of female
      parasites INTERPRETATION & CONCLUSION: In conclusion, C. bonducella- seed kernel
      extract and fractions showed microfilaricidal, macrofilaricidal and female
      sterilizing efficacy against L. sigmodontis and microfilaricidal and female
      sterilizing efficacy against B. malayi in animal models, indicating the potential
      of this plant in providing a lead for new antifilarial drug development.

PMID- 18820362
TI  - Expression of cell surface markers on methicillin resistant Staphylococcus aureus
      stimulated lymphocytes.
AB  - BACKGROUND & OBJECTIVE: Methicillin-resistant Staphylococcus aureus (MRSA) has
      gradually been increasing, new strategies in the treatment of MRSA infections are
      required. This depends on the understanding of the infection pathogenesis and the
      immune response. This study was therefore designed to determine the immune
      response which develops during MRSA infection and the role of chemokines in this
      response, and also to compare the results with the changes occurring after MSSA
      infection. METHODS: The expression of the surface markers of human lymphocytes
      stimulated by heat-killed MRSA or MSSA was analysed by flow cytometry. The
      chemokine levels in the lymphocytes culture supernatants stimulated or not
      stimulated by microorganisms were determined by ELISA. RESULTS: Human peripheral
      blood mononuclear cells (PBMCs) stimulated by MRSA the levels of CD4(+)CD25(+)
      regulatory T cells, CD69 expressions in the activated T lymphocytes, CD3(
      )CD16(+)CD56(+) NK cells and the levels of MIP-1alpha, MIP-1beta, MCP-1
      chemokines increased as compared to the cells not stimulated by MRSA. Although
      stimulation by MSSA caused an increase in CD25 expression after 24 h, the
      increase was found to be lower than the one caused by MRSA stimulation. The
      increase in CD69 expression was statistically significant compared to the cells
      stimulated by MRSA. Different from the cells stimulated by MRSA, no change was
      observed in the expressions of CD54 and CD3(-)CD16(+)CD56(+) NK cells in the
      cells stimulated by MSSA. INTERPRETATION & CONCLUSION: Our findings showed that
      cellular as well as humoral immunity are critical in MRSA infection and that T
      cell activation and the increase in chemokines may play a role in the regulation
      of immune response.

PMID- 18820363
TI  - Prevalence & predictors of alcohol use among college students in Ludhiana,
      Punjab, India.

PMID- 18820364
TI  - Rolling back malaria is possible.

PMID- 18820365
TI  - Solution to contentious issue of Article 31(f) of TRIPS agreement.

PMID- 18820367
TI  - NACO must clean up phony NGOs in India.

PMID- 18820368
TI  - Molecular mechanisms of action of imatinib mesylate in human ovarian cancer: a
      proteomic analysis.
AB  - BACKGROUND: Imatinib mesylate (Gleevec, Novartis, Basel, Switzerland) is a small
      molecule tyrosine kinase inhibitor with activity against ABL, BCR-ABL, c-KIT, and
      PDGFR alpha. Several clinical trials have evaluated the efficacy and safety of
      imatinib in patients with ovarian carcinoma who have persistent or recurrent
      disease following front-line platinum/taxane based chemotherapy. However, there
      is limited pre-clinical and clinical data on the molecular targets and action of
      imatinib in ovarian cancer. MATERIALS AND METHODS: Human ovarian cancer cells
      (A2780) were treated with imatinib mesylate for either 6 or 24 h. We employed a
      2D (two-dimensional) gel electrophoresis and mass spectrometry-based proteomics
      approach to identify protein expression patterns and signaling pathways that were
      altered in response to imatinib. Cells were analyzed for PDGFR alpha and AKT
      expression, which were then correlated with imatinib sensitivity. RESULTS: Using
      2D gel electrophoresis of overlapping pH ranges from pH 4 to 11, about 4,000
      protein spots could be analyzed reproducibly. Proteins whose levels changed
      between twofold to 30 fold were grouped according to whether changes were in the
      same direction at both time points of treatment with respect to the control, or
      changed their levels only at one of the time points. CONCLUSION: Differentially
      regulated proteins following imatinib treatment of A2780 cells involved the
      regulation of actin cytoskeleton, metabolic pathways, cell cycle, cell
      proliferation, apoptosis, cell junctions, and signal transduction. Thus, exposure
      of cells to imatinib produces complex changes in the cell that require further
      investigation.

PMID- 18820369
TI  - Identification of F-box/LLR-repeated protein 17 as potential useful biomarker for
      breast cancer therapy.
AB  - BACKGROUND: The expression and activity of ribonucleotide reductase (RR) has been
      associated with resistance to multiple drugs in human cancer. The use of
      antisense oligonucleotide drug, GTI-2040, a 20-mer phosphorothioate
      oligonucleotide complemented to the human RR M2 subunit mRNA, represents an
      effective strategy for inhibiting RR. The increased specificity due to the anti
      resistance effect of GTI-2040 may also lead to a more favorable therapeutic
      outcome. MATERIALS AND METHODS: To understand the molecular mechanism underlying
      RR inhibition, patients' blood samples were analyzed using multiple dimensional
      proteomics technology via matrix-assisted laser desorption and ionization time-of
      flight (MALDI-TOF) mass spectrometry. RESULTS: A major difference occurred at 5k
      m/z in the MALDI profile, which appeared only in the non-responsive group and
      diminished after GTI-2040 treatment. This specific peptide peak remained at the
      basal level in responsive patients. The peak was identified to represent the F
      box/LLR-repeat protein 17 (FBXL17) through nanoelectrospray ionization liquid
      chromatography-tandem mass spectrometry (nanoESI LC-MS/MS). Further
      characterization revealed that FBXL17 [corrected] directly interacts with the
      human RR M2 (RRM2) subunit to promote hRRM2 overexpression in the breast cancer
      cell line MCF-7. CONCLUSION: Validation of this protein using real-time RT-PCR
      indicates the F-box protein 17 (FBXL17) can serve as a therapeutic target and
      surrogate marker for breast cancer therapy.

PMID- 18820370
TI  - Phosphoproteome and transcriptome analyses of ErbB ligand-stimulated MCF-7 cells.
AB  - Cellular signal transduction pathways and gene expression are tightly regulated
      to accommodate changes in response to physiological environments. In the current
      study, molecules were identified that are activated as a result of intracellular
      signaling and immediately expressed as mRNA in MCF-7 breast cancer cells shortly
      after stimulation of ErbB receptor ligands, epidermal growth factor (EGF) or
      heregulin (HRG). For the identification of tyrosine-phosphorylated proteins and
      expressed genes, a SILAC (stable isotopic labeling using amino acids in cell
      culture) method and Affymetrix gene expression array system, respectively, were
      used. Unexpectedly, the overlapping of genes appeared in two experimental
      datasets was very low for HRG (43 hits in the proteome data, 1,655 in the
      transcriptome data, and 5 hits common to both datasets), while no overlapping
      gene was detected for EGF (15 hits in the proteome data, 211 hits in the
      transcriptome data, and no hits common to both datasets). The HRG overlapping
      genes included ERBB2, NEDD9, MAPK3, JUP and EPHA2. Biological pathway analysis
      indicated that HRG-stimulated molecular activation is significantly related to
      cancer pathways including bladder cancer, chronic myeloid leukemia and pancreatic
      cancer (p < 0.05). The proteome datasets of EGF and HRG contain molecules that
      are related to Axon guidance, ErbB signaling and VEGF signaling at a high rate.

PMID- 18820371
TI  - The small variant of the apoptosis-associated X-chromosome RBM10 gene is co
      expressed with caspase-3 in breast cancer.
AB  - BACKGROUND: There are very few studies on the final triggers of apoptosis, the
      caspases, in breast cancer. MATERIALS AND METHODS: Caspase-3 expression was
      studied by means of reverse transcript polymerase chain reaction (RT-PCR) in a
      series of 108 previously untreated patients with breast cancer. Expression levels
      were correlated with those obtained using the same technique of the apoptosis
      associated X-chromosome genes RBMX, RBM3, RBM10 small and RBM10 large variant;
      Bcl-2 and Bax; the angiogenesis-associated genes VEGF and CD105 (endoglin); hMAM
      and Nup88. The correlation with the expression of hormone receptors, c-erb-B2,
      mutant p53 and Ki-67, all measured by means of immunohistochemistry, was also
      studied, as well as that with standard clinical parameters such as histological
      type, tumor size, axillary metastasis and DNA-ploidy. RESULTS: The only
      statistically significant correlations observed between caspase-3 mRNA expression
      and the parameters tested were a direct one with both the Bax (p = 0.007) and the
      small variant of the X-chromosome RBM10 gene (p = 0.018), and an inverse one with
      the angiogenesis-associated CD105 (endoglin) gene (p = 0.044). CONCLUSION: These
      results indicate that very few genes are involved in the last steps of the
      apoptotic cascade in breast cancer, among them one of the X-chromosome RBM
      family. They also support the relatively unexplored link between apoptosis and
      angiogenesis.

PMID- 18820372
TI  - The proteome profile of two cell lines and their xenografts isolated from a
      patient with clear cell sarcoma (soft tissue melanoma).
AB  - We report the establishment of two novel clear cell sarcoma (CCS) cell lines
      (soft tissue melanoma) from a patient and the production of the corresponding
      xenografts after xenotransplantation of those cells to NOD/SCID mice. As no
      comprehensive study on the relevant proteomes of this type of cancer has been
      reported to date, proteomics technologies were applied in a first attempt to
      analyze the proteins of the two cell lines and their corresponding primary
      xenografts. Total protein extracts were separated by two dimensional gel
      electrophoresis (2-DE) and analysed by MALDI-MS and MALDI-MS-MS following in-gel
      digestion with trypsin. Protein identification was carried out by peptide mass
      fingerprint (PMF) and post source decay (PSD), respectively. Comparative analysis
      revealed that 124 proteins were common between the cell lines and the xenografts;
      249 proteins were found to be expressed only in the proteome of the cell lines,
      while 178 proteins were expressed only in the proteome of xenografts. Our results
      demonstrated that both cell lines and xenografts were positive for vimentin and
      S100 reported as markers for CCS. After functional analysis, 27 different protein
      groups were identified in the analysed proteomes, including apoptosis-related
      proteins, oncogenes and several proteins closely related to TP-53 and NF-kappa B
      pathways. Furthermore, the proteins nestin, stem cell growth factor CLC11 and mdr
      1, closely related to malignant-melanoma-initiating cells, were found to be
      expressed in both the cell lines and their corresponding xenografts. Since there
      are no data concerning protein expression in CCS, this study may contribute to
      the understanding of the molecular basis of the disease, while the cell lines as
      well as the developed xenografts may be used as tools for the development of new
      therapeutic strategies to tackle this rare but fatal malignancy.

PMID- 18820373
TI  - Importance of optimal infant and young child feeding (IYCF) in achieving
      millennium development goals.

PMID- 18820374
TI  - Pertussis and diphtheria immunization.

PMID- 18820375
TI  - Acellular pertussis vaccines pertinent issues.

PMID- 18820376
TI  - Management of malaria in children: update 2008.
AB  - JUSTIFICATION: The first guideline on diagnosis and management of malaria in
      children was formulated by Infectious Diseases Chapter of IAP in 2005. In
      subsequent year WHO proposed artemisinin based combination therapy in all cases
      of uncomplicated falciparum malaria. The number of falciparum malaria as well as
      multidrug resistant falciparum malaria cases are constantly on the rise. So there
      was need to revise the existing guideline. PROCESS: The first recommendations on
      the diagnosis and management of malaria in children were formulated in 2005. The
      same protocol was revised on 12 October 2007 in NIMHANS, Bangalore in the light
      of various recommendations of WHO, where all the members of the Task Force
      Committee on Malaria in Children were present. OBJECTIVE: To revise and update
      treatment guidelines for malaria with special reference to artemisinin based
      combination therapy. RECOMMENDATIONS: The need for Artemisinin based combination
      therapy (ACT) is emphasized in chloroquine resistant falciparum malaria.
      Monotherapy with artesunate will further increase the resistance. Once malaria
      treatment is initiated it should be completed. In severe malaria the maintenance
      dose of artesunate is revised.

PMID- 18820377
TI  - Performing TB research in children - issues to consider.

PMID- 18820378
TI  - Long-term prognosis of neonatal seizures - where are we?

PMID- 18820379
TI  - Intestinal failure - an Indian perspective.

PMID- 18820380
TI  - A profile of bacteriologically confirmed pulmonary tuberculosis in children.
AB  - OBJECTIVE: To describe the clinical profile of children with bacteriologically
      confirmed tuberculosis. STUDY DESIGN: A multicentric study was conducted in three
      hospitals in Chennai city between July 1995 and December 1997. Children aged 6
      months to 12 years with signs and symptoms suggestive of tuberculosis were
      investigated further. Clinical examination, chest radiograph, tuberculin skin
      test with 1 TU PPD and, sputum or gastric lavage for mycobacterial smear and
      culture were done for all and, lymph node biopsy when necessary. RESULTS: A total
      of 2652 children were registered and tuberculosis was bacteriologically confirmed
      in 201. Predominant symptoms were history of an insidious illness (49%), fever
      and cough (47%), loss of weight (41%) and a visible glandular swelling (49%).
      Respiratory signs were few and 62% were undernourished. Over half the patients
      with confirmed TB had normal chest X-ray. Abnormal X-ray findings included
      parenchymal opacities in 47% and hilar or mediastinal lymphadenopathy in 26%. The
      prevalence of isoniazid resistance was 12.6% and MDR TB 4%. CONCLUSIONS: Children
      with tuberculosis present with fever and cough of insidious onset.
      Lymphadenopathy is a common feature even in children with pulmonary TB. A
      significant proportion of children have normal chest X-rays despite positive
      gastric aspirate cultures. Drug resistance rates in children mirror the pattern
      seen in adults in this geographic area.

PMID- 18820381
TI  - The newborn with seizures -- a follow-up study.
AB  - OBJECTIVE: To determine the sequelae of neonatal seizures in a cohort of
      newborns, recruited over a six month period. DESIGN: Prospective hospital based
      study. SETTING: The neonatal intensive care unit (NICU) of a tertiary care
      hospital. PARTICIPANTS: 135 babies were recruited of whom 10 died and 25 were
      lost to follow up. METHODS: The cases were followed up over four months. RESULTS:
      68% of the babies followed up were normal; 32% had an abnormal neurological
      outcome. Seven (7%) developed post-neonatal epilepsy. Hypocalcemia was
      significantly associated with mortality (OR: 21.9; 95% CI: 1.2-391.2). No risk
      factors could be identified for post neonatal epilepsy. Presence of spike waves
      in the EEG was significantly related to abnormal neurological outcome (OR: 3.5;
      95% C.I. 1.2-10.8). CONCLUSIONS: Majority of neonates with seizures have a normal
      outcome with no developmental delay or neurological deficit. Predominantly spike
      waves in the EEG is predictive of abnormal neurological outcome.

PMID- 18820382
TI  - Permanent intestinal failure.
AB  - CONTEXT: Intestinal failure (IF) requires the use of parenteral nutrition as long
      as it persists and may be in case of persistence an indication for intestinal
      transplantation. EVIDENCE ACQUISITION: Literature search was performed both
      electronically and manually. RESULTS AND CONCLUSIONS: Biological evaluation of IF
      is becoming possible with the use of plasma citrulline as a marker of intestinal
      mass. Short bowel syndrome (SBS) is the leading cause of intestinal failure in
      infants while few epidemiological data are available to date. Data on morbidity
      and mortality in pediatric patients with SBS are very limited while long-term
      outcome seems to be improving. Other causes of intestinal failure include neuro
      muscular intestinal disease and congenital disease of enterocyte development. The
      management of IF should include therapies adapted to each type and stage of IF
      based on a multidisciplinary approach, in centers involving pediatric surgery,
      pediatric gastroenterology, parenteral nutrition expertise, home parenteral
      nutrition program, and liver-intestinal transplantation experience. Timing for
      referral of patients in specialized centers remains a crucial issue. The main
      causes of IF are briefly reviewed emphasizing the medico-surgical strategy for
      prevention and care-provision, adapted to each type and stage of IF.

PMID- 18820383
TI  - Exposed to varicella: is vaccination of any use now?

PMID- 18820384
TI  - 2008 World Drug Report: a more pragmatic approach needed to combat illicit drug
      use.

PMID- 18820385
TI  - Factors associated with treatment failure in childhood tuberculosis.
AB  - We retrospectively reviewed records of 541 children (315 boys) suffering from
      tuberculosis, median age 95 (range 2-180) months, to determine factors associated
      with treatment failure. 256 (47.3%) children had pulmonary tuberculosis (PTB)
      while 285 (52.7%) had extrapulmonary tuberculosis (EPTB). 459 (84.8%) children
      were cured and 82 (15.5%) had treatment failure. On bivariate analysis, AFB
      positivity [OR= 2.13 (95% CI 1.18- 3.85)], non-receipt of BCG vaccination during
      infancy [OR=1.73 (1.02- 2.91)] and EPTB [1.9 (1.16- 3.11)] were associated with
      treatment failure. On multivariate analysis, only extrapulmonary tuberculosis was
      significantly associated with treatment failure.

PMID- 18820386
TI  - Temperamental traits and psychological problems of children with bronchial
      asthma.
AB  - Children with persistent asthma were compared with an age and sex matched control
      group for psychological problems and temperamental traits. Childhood
      Psychopathology Measurement Schedule (CPMS) and Temperament Measurement Schedule
      were used to assess psychological problems and temperamental traits,
      respectively. 69% of children in the study group scored more than the cut-off
      score on the CPMS compared to 13% in the control group (P < 0.01). Children in
      the study group showed significantly more behavior problems, conduct symptoms,
      anxiety, depression and emotional problems compared to children in the control
      group. Children with asthma also received significantly low score on the
      temperament dimension of rhythmicity.

PMID- 18820387
TI  - Persistent pulmonary interstitial emphysema in a preterm infant.
AB  - Persistent pulmonary interstitial emphysema is a chronic disease reported in
      mechanically ventilated premature newborns. We describe a case of localized
      persistent pulmonary interstitial emphysema in a preterm infant without
      mechanical ventilation but on continuous positive airway pressure using nasal
      prongs. The condition resolved without surgery.

PMID- 18820388
TI  - Biotinidase deficiency.
AB  - A three month old baby presented with refractory seizures, dermatosis and
      persistent metabolic acidosis. Biotinidase deficiency was diagnosed on enzyme
      assay. Patient responded dramatically to biotin supplementation.

PMID- 18820389
TI  - Bartsocas-Papas syndrome.
AB  - We report three sibs born to a third degree consanguineous Indian family affected
      with Bartsocas Papas Syndrome. All the three pregnancies were complicated by
      severe oligohydramnios, which is not commonly seen with Bartsocas-Papas syndrome.

PMID- 18820390
TI  - Larsen syndrome.

PMID- 18820391
TI  - Calcinosis in juvenile dermatomyositis.

PMID- 18820392
TI  - Hand hygiene care.

PMID- 18820393
TI  - Creative leisure opportunities.
AB  - Creativity is a human characteristic that enables people and communities to adapt
      and thrive in changing circumstances. People spend the greater part of their
      lives engaging in a variety of activities that support health and well-being.
      Creativity can be expressed through many of the activities of everyday life,
      including work, family life, social interaction and leisure. When someone is
      unable to access a healthy range of activities, due to illness, disability or
      other circumstances, he will seek alternative ways of meeting his needs. For
      example, if a man is unable to work because of illness, he may choose to use his
      leisure time to express his creativity. Creative leisure activities can become an
      important part of an individual's strategies for coping with illness or
      disability; through promoting adaptation, creating meaningful goals and providing
      distraction from pain and anxiety. If a person finds it difficult to engage in
      creative leisure activities, due to illness or disability, it may be necessary to
      provide practical support or to stimulate the individual's own creative
      development.

PMID- 18820394
TI  - Using music in leisure to enhance social relationships with patients with complex
      disabilities.
AB  - Acquired and complex disabilities stemming from severe brain damage and
      neurological illness usually affect communication, cognitive, physical or sensory
      abilities in any combination. Improved understanding of the care needs of people
      with complex disabilities has addressed many functional aspects of care. However,
      relatives and carers can be left at a loss knowing how to provide or share in
      meaningful activities with someone who can no longer communicate or respond to
      their environment. As a result, the individual with complex needs can become
      increasingly isolated from their previous support network. Based on theoretical
      foundations for music as instinctive in human beings, this paper offers practical
      recommendations for the creative use of music for people with complex physical
      and sensory needs which prevent active participation in previous leisure
      pursuits. Recommendations are made for relatives and carers to manage the
      environment of an individual who has limited capacity to control their
      environment or make choices about leisure activities. Particular emphasis is
      given to activities which can be shared between a facilitator and the patient,
      thereby enhancing social relationships.

PMID- 18820395
TI  - The role of occupational therapy in leisure adaptation with complex neurological
      disability: a discussion using two case study examples.
AB  - This article looks at the importance of leisure as a key principle within
      occupational therapy practice. A review of current literature and two in-patient
      case studies are used to discuss the role of the Occupational Therapist in
      adapting leisure occupations for individuals with complex neurological
      disability. The article highlights the use of leisure as an occupation through
      which therapeutic goals can be achieved. Goals should underpin leisure, enabling
      an individual to participate in their chosen leisure occupations. It is
      recognised that there is importance in using a client-centred approach to ensure
      that meaningful occupations are used and that the occupation fits the needs of
      the individual and not the other way around. Working in this way, there is a
      benefit to individuals, assisting them to cope with loss and the onset of
      disability and also preventing occupational deprivation.

PMID- 18820396
TI  - When distress gives way to possibility: the relevance of leisure in adjustment to
      disability.
AB  - Previous research has suggested that leisure assists in coping with and adjusting
      to negative life events in at least four different ways: by being diverting, by
      generating hope, by restoring some aspects of self, and by affording a context
      for personal transformation. An assault to the brain, whether due to a stroke,
      chronic disease, injury or trauma, would be such an event and would likely by
      served by leisure in the same way. This paper reviews the supporting evidence
      regarding the value and utility of leisure in coping with and adjusting to living
      with a disability. The concept of posttraumatic growth is then examined and
      related research is reviewed with particular attention to the relevance of
      leisure. Finally, considerations are offered for incorporating leisure as an
      aspect of treatment and care for those working in neurorehabilitation settings.

PMID- 18820397
TI  - Adapting leisure activity for adults with neuropsychological deficits following
      acquired brain injury.
AB  - Adapting leisure activities is sometimes required for adults with
      neuropsychological deficits following acquired brain injury. Such adaptations are
      illustrated through a brief review of relevant literature and case vignettes
      describing both group-based and individual intervention provided within a
      holistic milieu-oriented neuropsychological rehabilitation programme. Particular
      emphasis is placed on the impact of cognitive deficits on a person's ability to
      engage in their desired activities. The personal meaning and psychological
      adjustment to injury is considered a crucial factor when considering adapting
      activity. The article will conclude with implications for clinical practice in
      other settings.

PMID- 18820398
TI  - Right leisure: serious, casual, or project-based?
AB  - Leisure as a tool for rehabilitating people with neuro-disabilities is well
      established. Yet, despite significant progress in this area, problems remain in
      the way leisure is used for this purpose. One, as yet, unresolved problem is how
      to determine which leisure activity or activities will be attractive to people
      with particular disabilities. Another is how to counteract the persistent,
      dominant public view that real personal worth is measured according to the work
      people do rather than the leisure they pursue. The third is to inform
      practitioners, many of whom are unaware of recent advances in leisure theory,
      about these advances, which can help them solve the first problem and adapt to
      the second. The main body of this paper presents such a theory - the serious
      leisure perspective. It synthesizes three main forms of leisure, showing, at
      once, their distinctive features, similarities, and interrelationships. The forms
      are serious, casual, and project-based leisure. A review of the research on neuro
      rehabilitation follows. Some implications of the Perspective for neuro
      rehabilitation are then presented, including ways practitioners can introduce
      clients to certain types of leisure, encourage them to pursue the types chosen,
      and help them develop an optimal leisure lifestyle.

PMID- 18820399
TI  - Access to computer-based leisure for individuals with profound disabilities.
AB  - Advances in computer technology and the Internet have meant that more and more
      occupations can be made available to disabled individuals, including occupations
      generally considered to be leisure. However, computers and the Internet also
      provide barriers to access for these individuals. This article discusses some of
      these barriers, solutions to them and highlights the complexities involved in the
      provision of a computer-based assistive technology solution for access to leisure
      for a profoundly disabled young lady. It also points out the need for the input
      of a highly skilled, multi-disciplinary team in the assessment for and provision
      of such a system.

PMID- 18820400
TI  - Tailoring leisure to suit a wider audience through creative event planning with a
      multi-sensory approach.
AB  - Caregiving for long-term conditions is increasingly focused on holistic "person
      centred" care [9,34], with leisure and recreation providing an important and
      essential part of maintaining quality of life. This article documents examples of
      large leisure events and creative projects. These were adapted for, and
      considered to be suitable and supportive of, the needs of adults with complex and
      profound disability as a result of neurological damage or disease. The ways in
      which events have been tailored by the Recreation and Leisure Service,
      incorporating sensory elements with the view to increased accessibility and
      enjoyment for participants, are highlighted in this article. The ultimate
      challenge faced was programming events to suit more than 170 people aged over 18
      who each have particular preferences, varied interests and abilities including
      the most profound physical and cognitive impairments. These developments and
      changes in format have encouraged essential input from participants themselves
      and their families and carers, whilst involving the wider community; volunteers,
      external charitable groups and professional organisations.

PMID- 18820401
TI  - Exploring the multi-sensory environment as a leisure resource for people with
      complex neurological disabilities.
AB  - The problems experienced by people with neurological disabilities create barriers
      to participation in leisure activities. Particular common features include
      cognitive deficits (attention, executive functioning, language and memory),
      functional difficulties (in activities of daily living), psychomotor impairment
      (dyspraxia and poor co-ordination), and behavioural difficulties (aggression,
      agitation, and wandering). The Multi-sensory environment (MSE) has the potential
      to accommodate some of these problems experienced by people with neurological
      disabilities and, as such, is a valuable leisure resource. Multi-sensory activity
      can address individual sensory needs, such as offering a stronger stimulus if
      initial attempts are unnoticed, and be offered alongside familiar activities and
      routines to enhance sensory awareness. If the complexity of the activity,
      individual needs, and MSE demands are matched, engagement in this activity may be
      achieved. The Pool Activity Level Occupational Profiling Tool can provide a
      protocol from which MSE activity may be facilitated. By using this tool the MSE
      fits well within the World Health Organisation International Classification of
      functioning, Disability and Health by facilitating participation and reducing
      environmental barriers.

PMID- 18820402
TI  - Casual leisure and the sensory diet: a concept for improving quality of life in
      neuropalliative conditions.
AB  - This case report describes the leisure lifestyle of two individuals with
      neuropalliative conditions who expressed themselves satisfied with their use of
      leisure time and whose leisure occupations were based around sensory stimulation
      to each of the five senses, proprioception and vestibular stimulation in turn. It
      evaluates the concept of leisure as a means of giving a meaning to life and
      therefore increasing quality of life, suggests greater use of the existing
      sensory diet framework in the domain of neuropalliative conditions and proposes a
      direction for future research in order to provide casual leisure opportunities
      for individuals with severe cognitive dysfunction in order to improve their
      quality of life.

PMID- 18820403
TI  - Adult zebrafish as a model for successful central nervous system regeneration.
AB  - Adult fish, in contrast to mammals, are capable of regenerating axonal tracts as
      well as cells and even entire tissues in the central nervous system (CNS). The
      zebrafish is a powerful genetic model for studies on the developing CNS and is
      now emerging as a CNS regeneration model. Here we review recent progress in adult
      regeneration paradigms in zebrafish ranging from axonal re-growth models to those
      of tissue regeneration. Moreover, we review the tools that have become available
      in zebrafish to elucidate the factors contributing to successful CNS
      regeneration. Since many molecular pathways are shared between zebrafish and
      mammals, it is hoped that insights from zebrafish may contribute to future
      therapeutic approaches in CNS injury and disease.

PMID- 18820404
TI  - Cell adhesion molecules of the immunoglobulin superfamily in axonal regeneration
      and neural repair.
AB  - Cell adhesion molecules (CAMs) play important roles in cell-cell and cell
      extracellular matrix interactions in both mature and developing nervous system.
      During development, they are involved in cell migration, axon guidance, target
      recognition, and synapse formation; while in the mature nervous system, they
      maintain synaptic connections, cell-cell contacts, and neuron-glial interactions.
      Injuries to the nervous systems break the stable state of the tissues and the
      repair of damaged tissues and regeneration of axons require the participation of
      CAMs both as adhesion molecules and as signal transduction molecules. One group
      of the well-studied CAMs in the nervous system is the immunoglobulin superfamily
      including L1 and neural cell adhesion molecule (NCAM). This review will be
      focussed on the involvement of L1, NCAM, and polysialylated NCAM in neural repair
      and axon regeneration after nerve injury and their potential applications in the
      treatment of CNS injury.

PMID- 18820405
TI  - Mechanisms of CNS myelin inhibition: evidence for distinct and neuronal cell type
      specific receptor systems.
AB  - Following injury to the adult mammalian central nervous system, regenerative
      growth of severed axons is very limited. The lack of neuronal repair is often
      associated with significant functional deficits, and depending on the severity of
      injury, may result in permanent paralysis distal to the site of injury. A
      detailed understanding of the molecular mechanisms that limit neuronal growth in
      the injured spinal cord is an important step toward the development of specific
      strategies aimed at restoring functional connectivity lost as a consequence of
      injury. While rapid progress is being made in defining the molecular identity of
      CNS growth inhibitory constituents, comparatively little is known about their
      receptors and downstream signaling mechanisms. Emerging new evidence suggests
      that the mechanisms for myelin inhibition are likely to be complex, involving
      multiple and distinct receptor systems that may operate in a redundant manner.
      Furthermore, the relative contribution of a specific ligand-receptor system to
      bring about growth inhibition may greatly vary among different neuronal cell
      types. Myelin-associated glycoprotein (MAG), for example, employs different
      mechanisms to inhibit neurite outgrowth of cerebellar, sensory, and retinal
      ganglion neurons in vitro. Nogo-A harbors distinct growth inhibitory regions,
      which employ different signaling mechanisms. The Nogo-66 receptor 1 (NgR1), a
      shared ligand binding component in a receptor complex for Nogo-66, MAG, and OMgp,
      participates in neuronal growth cone collapse to acutely presented myelin
      inhibitors, but is dispensable for longitudinal neurite outgrowth inhibition on
      substrate-bound Nogo-66, MAG, OMgp, or crude CNS myelin in vitro. Consistent with
      the idea of cell-type specific mechanisms for myelin inhibition, different types
      of CNS neurons possess very different regenerative capacities and respond
      differently to experimental treatment strategies in vivo. We speculate that
      differences in regenerative axonal growth among different fiber systems are a
      reflection of their intrinsic ability to elongate axons and their distinct cell
      surface receptor profiles to respond to the growth inhibitory extracellular
      milieu. The existence of cell type specific mechanisms to impair regenerative
      axonal growth in the CNS may have important implications for the development of
      treatment strategies. Depending on the fiber tract injured, different ligand
      receptor systems may need to be targeted in order to elicit robust and long
      distance regenerative axonal growth.

PMID- 18820406
TI  - Axonal guidance molecules and the failure of axonal regeneration in the adult
      mammalian spinal cord.
AB  - A wide variety of molecules are involved as attractive or repulsive guidance cues
      in the developing nervous system. Some of these molecules are also expressed in
      the CNS of adult mammals where, following injury, they may repel regenerating
      axons, inhibit axonal regrowth, or control the behaviour of other cells important
      for the development of the meningeal and glial scars or the immune response to
      injury. Ephrins, semaphorins, Slits, Netrins, bone morphogenetic proteins (BMPs)
      and Wnts are among the most likely molecules to be involved in limiting axonal
      regeneration in the injured spinal cord. The receptors for these molecules are
      not universally expressed by neurons but there is evidence that ephrins and
      semaphorins limit regeneration of particular classes of axon into spinal cord
      lesion sites. It is likely that other repulsive guidance cues will also
      differentially affect the regeneration of specific tracts within the spinal cord.
      In addition to direct effects on axonal regeneration, many axonal guidance
      molecules have effects on glial, meningeal or immune system cells which also
      modulate the responses of CNS tissue to injury.

PMID- 18820407
TI  - Proteoglycans in the central nervous system: plasticity, regeneration and their
      stimulation with chondroitinase ABC.
AB  - After injury to the mammalian central nervous system (CNS), neurons are not able
      to regenerate their axons and recovery is limited by restricted plasticity. Axon
      regeneration is inhibited by the presence of the various inhibitory molecules,
      including chondroitin sulfate proteoglycans (CSPGs) which are upregulated around
      the injury site. Plasticity after the end of critical periods is restricted by
      extracellular matrix changes, particularly the formation of CSPG-containing
      perineuronal nets. Enzymatic removal of chondroitin sulfate (CS) chains with
      chondroitinase ABC promotes axon regeneration and reactivates plasticity. This
      review details the structures and properties of the different CSPGs in the normal
      and damaged CNS, the use of the enzyme chondroitinase ABC to promote neural
      regeneration and plasticity, and discusses mechanisms of action and possible
      therapeutic uses of this enzyme.

PMID- 18820408
TI  - Regeneration of axons in the visual system.
AB  - This review will describe the unique advantages that are offered by the visual
      system of mammals and other vertebrates for studying the regenerative responses
      of the central nervous system (CNS) to injury, and recent insights provided by
      such studies. In the mouse and rat visual system a variety of experimental
      paradigms promote survival of retinal ganglion cells (RGC) and optic nerve
      regeneration, probably through stimulation by neurotrophic factors (NTF) either
      directly, or indirectly through retinal astrocyte/Muller cell intermediary
      activation. NTF induce disinhibition of axon growth through regulated
      intramembranous proteolysis of p75NTR, and the inactivation of RhoA and EGFR
      signalling. The concomitant release of metalloproteinases (MMP) and plasminogen
      activators from RGC axons, and tissue inhibitors of metalloproteinases from optic
      nerve glia repress scarring and thereby reduce titres of scar-derived inhibitory
      ligands expressed in the wound. MMP also degrade myelin-derived inhibitory
      ligands along regenerating axon trajectories after regulated release from glia at
      the growing front of regenerating RGC axons. Optic nerve transection induces
      apoptosis of RGC which is blocked by anti-apoptotic regimes and thus, in
      combination with blockers of axon-growth inhibitory signalling and promoters of
      axon growth may be a therapeutic formula for promoting sustained axon
      regeneration. All these findings in the visual system are translatable to the CNS
      as a whole and thus strategies that successfully promote visual axon regeneration
      will be equally effective elsewhere in the CNS. Future developments likely to
      advance the field of regenerative research include a greater understanding of
      phylogenetic differences in the response of the CNS to injury, the role of NTF,
      cAMP, EGFR, glia/neuron interactions in disinhibiting and promoting axon growth,
      the control of neuron death, and effective drug delivery.

PMID- 18820409
TI  - Axon regeneration after spinal cord injury: insight from genetically modified
      mouse models.
AB  - The use of genetically modified mice to study axon regeneration after spinal cord
      injury has served as a useful in vivo model for both loss-of-function and gain-of
      function analysis of candidate proteins. This review discusses the impact of
      genetically modified mice on axon regeneration after spinal cord injury in the
      context of axon growth inhibition by myelin, the glial scar, and chemorepellent
      molecules. We also discuss the use of mice which transgenically express
      fluorescent proteins in specific axons for increasing our understanding of how
      spinal cord axons behave after injury.

PMID- 18820410
TI  - Promoting central nervous system regeneration: lessons from cranial nerve I.
AB  - The olfactory nerve differs from cranial nerves III-XII in that it contains a
      specialised type of glial cell, called 'olfactory ensheathing cell' (OEC), rather
      than Schwann cells. In addition, functional neurogenesis persists postnatally in
      the olfactory system, i.e. the primary olfactory pathway continuously rebuilds
      itself throughout adult life. The presence of OECs in the olfactory nerve is
      thought to be critical to this continuous growth process. Because of this
      intrinsic capacity for self-repair, the mammalian olfactory system has proved as
      a useful model in neuroregeneration studies. In addition, OECs have been used in
      transplantation studies to promote pathway regeneration elsewhere in the nervous
      system. Here, we have reviewed the parameters that allow for repair within the
      primary olfactory pathway and the role that OECs are thought to play in this
      process. We conclude that, in addition to intrinsic growth potential, the
      presence of an aligned substrate to the target structure is a fundamental
      prerequisite for appropriate restoration of connectivity with the olfactory bulb.
      Hence, strategies to promote regrowth of injured nerve pathways should
      incorporate usage of aligned, oriented substrates of OECs or other cellular
      conduits with additional intervention to boost neuronal cell body responses to
      injury and/or neutralisation of putative inhibitors.

PMID- 18820412
TI  - Transplantation of embryonic neurones to replace missing spinal motoneurones.
AB  - Loss of spinal motoneurones results in severe functional impairment. The most
      successful way to replace missing motoneurones is the use of embryonic
      postmitotic motoneurone grafts. It has been shown that grafted motoneurones
      survive, differentiate and integrate into the host cord. If grafted motoneurones
      are provided with a suitable conduit for axonal regeneration (e.g. a reimplanted
      ventral root) the grafted cells are able to grow their axons along the whole
      length of the peripheral nerves to reach muscles in the limb and restore
      function. Grafted motoneurones show excellent survival in motoneurone-depleted
      adult host cords, but the developing spinal cord appears to be an unfavourable
      environment for these cells. The long term survival and maturation of the grafted
      neurones are dependent on the availability of a nerve conduit and one or more
      target muscles, no matter whether these are ectopic nerve-muscle implants or limb
      muscles in their original place. Thus, grafted and host motoneurones induce
      functional recovery of the denervated limb muscles when their axons regenerate
      into an avulsed and reimplanted ventral root. On the other hand, motoneurone
      enriched embryonic grafts placed into a hemisection cavity in the cervical spinal
      cord induce axonal regeneration from great numbers of host motoneurones, possibly
      by the bridging effect of the grafts. In this case the regenerating host
      motoneurones reinnervate their original target muscles while the graft provides
      few axons for the reinnervation of muscles. These results suggest that
      reconstruction of the injured spinal cord with embryonic motoneurone-enriched
      spinal cord graft is a feasible method to improve severe functional motor
      deficits.

PMID- 18820413
TI  - Root repair review: basic science background and clinical outcome.
AB  - Spinal nerve root injuries have a profound effect on the different parts (PNS and
      CNS) of the root itself as well as the pertinent spinal cord segment. A root
      avulsion from the spinal cord is a longitudinal spinal cord injury. There is
      degeneration of sensory and motor axons, loss of synapses, deterioration of local
      segmental connections, nerve cell death and reactions among non neuronal cells
      with scar formation, i.e. a cascade of events similar to those known to occur in
      any injury to the spinal cord. For function to be restored, nerve cells must
      survive and there must be regrowth of new nerve fibres along a trajectory
      consisting of CNS growth-inhibitory tissue in the spinal cord as well as PNS
      growth-promoting tissue in nerves. Problems in PNS regeneration such as non
      directional growths and unspecific reinnervation of target organs lead to
      unpredictable sensorimotor activity and conspires against a useful recovery of
      function. From the results of basic science experiments, a surgical strategy to
      treat root avulsion with spinal cord injury has been developed. In humans this
      technique is currently the most promising treatment of any spinal cord injury,
      with return of useful function together with pain alleviation in cases where all
      nerves to the extremity have been avulsed from the spinal cord. At present the
      shortcomings of this technique are proportionate to the delay before surgery,
      which leads to death of nerve cells and incomplete and unpredictable recovery. In
      order to improve this situation and achieve further recovery of useful function
      including sensory perceptions and to fully alleviate pain it is necessary to
      pursue research and development of both basic and clinical science.

PMID- 18820411
TI  - Don't fence me in: harnessing the beneficial roles of astrocytes for spinal cord
      repair.
AB  - Astrocytes comprise a heterogeneous cell population that plays a complex role in
      repair after spinal cord injury. Reactive astrocytes are major contributors to
      the glial scar that is a physical and chemical barrier to axonal regeneration.
      Yet, consistent with a supportive role in development, astrocytes secrete
      neurotrophic factors and protect neurons and glia spared by the injury. In
      development and after injury, local cues are modulators of astrocyte phenotype
      and function. When multipotent cells are transplanted into the injured spinal
      cord, they differentiate into astrocytes and other glial cells as opposed to
      neurons, which is commonly viewed as a challenge to be overcome in developing
      stem cell technology. However, several examples show that astrocytes provide
      support and guidance for axonal growth and aid in improving functional recovery
      after spinal cord injury. Notably, transplantation of astrocytes of a
      developmentally immature phenotype promotes tissue sparing and axonal
      regeneration. Furthermore, interventions that enhance endogenous astrocyte
      migration or reinvasion of the injury site result in greater axonal growth. These
      studies demonstrate that astrocytes are dynamic, diverse cells that have the
      capacity to promote axon growth after injury. The ability of astrocytes to be
      supportive of recovery should be exploited in devising regenerative strategies.

PMID- 18820414
TI  - Occupational therapists' expertise in work rehabilitation and ergonomics.

PMID- 18820415
TI  - History of ergonomics and occupational therapy.
AB  - Ergonomics is commonly known as "the scientific study of human work" [14, p. 3]
      and "the application of scientific information concerning human beings to the
      design of objects, systems, and environments" (p. 4). The American Occupational
      Therapy Association defines occupational therapy as "skilled treatment that helps
      individuals achieve independence in all facets of their lives. It gives people
      the 'skills for the job of living' necessary for independent and satisfying lives
      [1]." Both professions share common backgrounds. Occupational therapy has been
      involved in health care and ergonomics is looking for its place in the health
      care field.

PMID- 18820416
TI  - Towards improved measurement of cognitive and behavioural work demands.
AB  - Determination of the cognitive and behavioural demands of work is an important
      part of holistic workplace intervention. Attention to these factors is especially
      important when developing return-to-work programs for persons with reduced
      cognitive, behavioural or psycho-emotional capacity, and when designing risk
      management programs in organizations. Occupational therapists have the background
      knowledge and skills to assess these components of work, but often lack valid and
      reliable measurement tools. This paper reports on three field studies that
      assessed the reliability and validity of ratings made by novice users of the City
      of Toronto Job Demands Analysis, which includes a measure of cognitive and
      behavioural work demands. Numerous challenges to accuracy and reliability that
      are common to empirical measurement were disclosed, including the necessity for
      clear and strong definitions, and the importance of thorough rater training.
      Implications for therapist training and mentorship are discussed.

PMID- 18820417
TI  - Predictive validity of a functional capacity evaluation: the physical work
      performance evaluation.
AB  - The predictive validity of a Functional Capacity Evaluation, the Physical Work
      Performance Evaluation (PWPE), was examined in 30 workers compensation patients
      with musculoskeletal dysfunction who participated in an industrial rehabilitation
      program. Return-to-work recommendations were made by comparing the discharge PWPE
      to the physical requirements of the job. Kappa coefficients were used to compare
      PWPE recommendations to actual work at discharge, 3 months and 6 months.
      Substantial agreement was found between PWPE recommendations at all three follow
      up points. This study provides preliminary evidence in support of the predictive
      validity of the PWPE for making return-to-work recommendations at the conclusion
      of an industrial rehabilitation program.

PMID- 18820418
TI  - A study of the effectiveness of ergonomically-based functional screening tests
      and their relationship to reducing worker compensation injuries.
AB  - OBJECTIVES: This paper summarizes a series of studies of the effectiveness of
      ergonomically based functional screening tests for post offer pre-placement of
      applicants for physically demanding jobs, and their relationship to reducing
      worker compensation injuries. Three predictive validation studies and a meta
      analysis of injury rates pre- and post-implementation of physical ability testing
      at 175 locations are included. METHODS: The strength and energy expenditure
      demands of physically-strenuous warehouse jobs in three industries were
      documented through ergonomic analysis. A battery of strength and endurance tests
      were developed to assess applicants' abilities to meet the measured physical
      demands. Predictive validation studies were performed for the jobs in each of the
      three industries. In each study, new-hires were given the physical ability test
      battery and then placed on the job. Management was not informed of the results of
      the tests. Injury experience and work history were then monitored over a two year
      period in each study. Injury rates and retention were then compared for
      individuals who passed and individuals who failed the battery. As the battery was
      implemented in other locations, the injury rate for individuals starting
      employment in the year prior to implementation was compared to the injury rate
      for individuals starting employment in the year after implementation.
      CONCLUSIONS: A meta-analysis of the three predictive validation studies indicated
      that new-hires who passed the battery had a 47% lower worker compensation injury
      rate and 21% higher retention. A meta-analysis of the 175 pre/post-implementation
      studies indicated a 41% reduction in worker compensation injuries associated with
      implementation of ergonomically based physical ability tests.

PMID- 18820419
TI  - Lowering nursing injuries using post offer pre-employment testing.
AB  - BACKGROUND AND PURPOSE: Nursing injuries are alarmingly high in the healthcare
      system. The rate of injuries adds to the shortage of nurses that are already
      employed. Preventing nursing injuries has focused on utilizing patient handling
      equipment. This project used post offer pre employment testing to attempt to
      control the injuries of nurses in a healthcare facility. OUTCOMES: Injuries were
      significantly lower in the employment pool that was tested when compared the
      nursing staff that had not been tested. Five injuries were reported in the tested
      group, resulting in $1,778 spent on the injuries, whereas the non-tested group
      had 54 injuries totaling $26,208. The total return on investment by this program
      was $4,541,059. DISCUSSION: Post Offer Pre employment testing can be a cost
      effective way to decrease the amount of injuries with nursing staff.

PMID- 18820420
TI  - Using the ICF as a conceptual framework to guide ergonomic intervention in
      occupational rehabilitation.
AB  - Traditional treatment of work-related musculoskeletal disorders focuses on the
      body functions and body structures aspects of the injury, with little or no
      attention paid to ergonomics as a form of treatment. The use of ergonomics in
      preventing disability in injured workers is a relatively new area of study. There
      are a number of factors that may contribute to the lack of emphasis on ergonomic
      interventions in the prevention of disability following musculoskeletal injury.
      For instance, a review of the knowledge base suggests that there is a lack of a
      formal conceptualization or standardized approach to ergonomics in the return to
      work process. In part, this lack of consistency may be due to the varied
      disciplinary backgrounds of ergonomists, leading individuals to view ergonomics
      from a specific perspective, rather than utilizing a transdisciplinary approach.
      The purpose of this paper is to introduce a new practice model of occupational
      rehabilitation ergonomics. The model draws upon the International Classification
      of Functioning, Disability, and Health (ICF) and merges this with basic ergonomic
      and rehabilitation principles.

PMID- 18820421
TI  - Return to work with chronic low back pain: using an evidence-based approach along
      with the occupational therapy framework.
AB  - This paper will attempt to apply the occupational therapy framework [1] along
      with an evidence-based approach and an occupation-based intervention with a
      population of workers with chronic low back pain (CLBP) to help them return to
      work and maintain their work status. This paper will focus primarily on those
      clients with CLBP who still have a link to their employment but who do not
      perceive themselves as being capable to go back to their job despite conflicting
      opinions from other stakeholders (primary health care professionals, employer or
      insurer). They are being evaluated in occupational therapy shortly before return
      to work and followed until their optimal functional capacities are reached. This
      means that either all functional goals related to the actual physical demands of
      their job have been reached or that further treatment does not result in
      functional improvement.

PMID- 18820422
TI  - Occupational therapy - meeting the needs of older adult workers?
AB  - OBJECTIVE: The purpose of this phenomenological study was to explore and better
      understand (a) why aging workers continue to work past retirement age, (b) how
      aware occupational therapists are of the needs of the growing demographic of the
      aging worker, and (c) potential occupational therapy interventions that could
      better help this population. METHOD: This study was conducted with a mixed method
      design approach, specifically the parallel/simultaneous design, which consisted
      of both qualitative and quantitative investigation. The quantitative portion of
      the study focused on data obtained from the surveys and the qualitative portion
      was based on phenomenological interviews of aging workers. RESULTS: Themes
      emerging from the interviews demonstrate the importance of health promoting
      habits and family support in providing the critical foundation to maintain
      employment past age 55. Financial stability was a key motivator which compelled
      the interviewees to continue working. The older workers had no planned date for
      retirement and felt confident that the knowledge and life experience they offered
      were important qualities they brought to the workplace. The survey showed a need
      for occupational therapists to become more responsive to the growing demographic
      of older adult workers as they reported limited service enhancement and expansion
      for this group. CONCLUSION: Aging workers are prime candidates for occupational
      therapy. However, the profession appears to be overlooking opportunities to meet
      the needs of these productive community members. Occupational therapists need to
      better respond to the physical, social, psychological, cognitive, and
      environmental challenges faced by this well population. The authors challenge
      occupational therapists to alter services, seek funding and obtain continuing
      education so they are better equipped to establish and enhance effective programs
      for this growing population.

PMID- 18820423
TI  - A single-subject design of ergonomic intervention effectiveness for university
      employees in a new facility.
AB  - As clinicians are searching for evidence to support their practice interventions,
      it is sometimes hard to find the "real-world" studies that incorporate the
      complexities of actual practice. Following calls in the public health, nursing
      and medical literature for clinicians to participate in practice-based evidence,
      this pilot study explores the effectiveness of a single-subject design for
      practice-based evidence. Twenty-five "well" university employees participated in
      an ergonomic intervention over the course of one academic semester that consisted
      of a 15 min ergonomic intake session, a 45 min group hands-on ergonomic
      educational session and a 15 min individual ergonomic consult in their offices.
      Participants were sent postural comfort surveys weekly and their subjective
      ratings were analyzed to determine the effectiveness of the intervention to
      decrease their perceived postural discomfort at a computer work station. Twenty
      one of the twenty-five participants reported an improvement in postural comfort
      over the course of the study. This pilot study suggests that further
      investigation needs to be conducted to determine the effectiveness of hands-on
      ergonomic education and consultation for well populations working at computer
      workstations.

PMID- 18820424
TI  - Participatory ergonomics intervention in a sterile processing center: a case
      study.
AB  - The following case study describes an ergonomics intervention program, designed
      and implemented by an occupational therapist (OT), which included principles of
      participatory ergonomics, had full support of management and administration, and
      addressed the work, worker, and environment. The ergonomics program took place in
      the Sterile Processing Center (SPC) of a 398 bed, mid-western hospital. The SPC
      was responsible for the collection, sterilization, and reassembling of hospital
      surgical equipment. The 30 employees of the SPC were vulnerable to injury, having
      experienced 19 in only two years (of the 19 injuries, 9 were WMSD or ergonomics
      related injuries). Over a two and a half year period, the OT and SPC manager
      conducted ergonomic evaluations, implemented employee training, designed a new
      SPC department, and modified work processes and equipment. In the year following
      the training and changes, the SPC staff experienced no injuries. Because of it's
      success, the program is continuing on a quarterly basis to ensure new problems
      are addressed quickly, new processes or equipment are evaluated, and new staff
      are properly trained.

PMID- 18820425
TI  - Occupational therapists' critical value in work rehabilitation and ergonomics.

PMID- 18820426
TI  - The empowerment of people with disabilities through qualitative research.
AB  - The purpose of this article is to explore the use of qualitative research in
      vocational rehabilitation as a means of empowering people with disabilities to
      (a) take greater control of their lives and (b) directly inform public policy and
      vocational rehabilitation service delivery. After exploring various definitions
      of the construct empowerment, we provide a rationale for the use of qualitative
      research as an empowerment mechanism based on (a) philosophies espoused by
      leaders of the independent living movement, (b) disability legislation, and (c) a
      multi-constituency call for more consumer involvement in research. We then
      describe empirical properties of various qualitative methodologies that lend
      themselves to consumer empowerment. The article concludes with several examples
      of qualitative approaches to scientific inquiry from the rehabilitation
      literature that include many of the empowerment aspects described herein.

PMID- 18820427
TI  - Temporal and spatial downregulation of Arabidopsis MET1 activity results in
      global DNA hypomethylation and developmental defects.
AB  - DNA methylation is an epigenetic mechanism for gene silencing. In Arabidopsis,
      MET1 is the primary DNA methyltransferase that maintains CG DNA methylation.
      Plants having an overall reduction of MET1 activity, caused by a met1 mutation or
      a constitutively expressed MET1 antisense gene, display genome hypomethylation,
      inappropriate gene and transposon transcription, and developmental abnormalities.
      However, the effect of atransient reduction in MET1 activity caused by inhibiting
      MET1 expression in a restricted set of cells is not known. For this reason, we
      generated transgenic plants with a MET1 antisense gene fused to the DEMETER (DME)
      promoter (DME:MET1 a/s). Here we show that DME is expressed in leaf primordia,
      lateral root primoridia, in the region distal to the primary root apical
      meristem, which are regions that include proliferating cells. Endogenous MET1
      expression was normal in organs where the DME:MET1 a/s was not expressed.
      Although DME promoter is active only in a small set of cells, these plants
      displayed global developmental abnormalities. Moreover, centromeric repeats were
      hypomethylated. The developmental defects were accumulated by the generations.
      Thus, not maintaining CG methylation in a small population of proliferating cells
      flanking the meristems causes global developmental and epigenetic abnormalities
      that cannot be rescued by restoring MET1 activity. These results suggest that
      during plant development there is little or no short-term molecular memory for
      reestablishing certain patterns of CG methylation that are maintained by MET1.
      Thus, continuous MET1 activity in dividing cells is essential for proper patterns
      of CG DNA methylation and development.

PMID- 18820428
TI  - Computational identification of site-specific transcription factors in
      Drosophila.
AB  - Site-specific transcription factors (TFs) recognise their target genes in a
      sequence- or conformation-dependent manor. In contrast to the basal TFs that are
      the general facilitators of gene expression, their site-specific interaction
      partners are tissue- or condition-specific. Thus, site-specific TFs constitute
      the major prerequisite for the modular expression programmes that drive metazoan
      development. This article deals with the computational identification of TFs (how
      to find them in genomes) and with online resources such as the FlyTF database of
      Drosophila site-specific TFs (how to find them online).

PMID- 18820429
TI  - Transcriptional perspectives from San Diego.

PMID- 18820430
TI  - A proteome catalog of Drosophila melanogaster: an essential resource for targeted
      quantitative proteomics.
AB  - Proteomic analyses are critically important for systems biology because important
      aspects related to the structure, function and control of biological systems are
      only amenable by direct protein measurements. It has become apparent that the
      current proteomics technologies are unlikely to allow routine, quantitative
      measurements of whole proteomes. We have therefore suggested and largely
      implemented a two-step strategy for quantitative proteome analysis. In a first
      step, the discovery phase, the proteome observable by mass spectrometry is
      extensively analyzed. The resulting proteome catalog can then be used to select
      peptides specific to only one protein, so-called proteotypic peptides (PTPs). It
      represents the basis to realize sensitive, robust and reproducible measurements
      based on targeted mass spectrometry of these PTPs in a subsequent scoring phase.
      In this Extra View we describe the need for such proteome catalogs and their
      multiple benefits for catalyzing the shift towards targeted quantitative
      proteomic analysis and beyond. We use the Insulin signaling cascade as a
      representative example to illustrate the limitations of currently used proteomics
      approaches for the specific analysis of individual pathway components, and
      describe how the recently published Drosophila proteome catalog already helped to
      overcome many of these limitations.

PMID- 18820431
TI  - Comparative neuroanatomy and genomics of hugin and pheromone biosynthesis
      activating neuropeptide (PBAN).
AB  - The Drosophila hugin gene encodes a prepropeptide that can potentially generate
      several neuropeptides.(1) The gene is expressed in 20 cells of the subesophageal
      ganglion (SOG) that are involved in modulating feeding behavior.(2) One of the
      hugin neuropeptides shares homology with mammalian neuromedin U8 (NmU8), which
      has been shown to regulate feeding behavior in rodents.(3,4) Recent clonal
      analysis indicated that each hugin expressing neuron projects to one of four main
      targets: the protocerebrum, the ventral nerve cord, the pharynx and the corpora
      cardiaca.(5) In addition all hugin neurons send short neurites to a novel region
      ventro-lateral to the foramen, which we suggested could be the tritocerebrum. In
      this short article, we discuss two specific issues brought up by these analyses.
      One concerns the polarity of hugin neurons. The other is an evolutionary
      perspective on the processing of hugin neuropeptides in light of new data from
      mass spectrometric and genomic analyses.

PMID- 18820432
TI  - What makes a fly enter diapause?
AB  - Diapause is a dormant state that insects may undergo as a response to changing
      environmental conditions. In flies, like many insects inhabiting temperate zones,
      diapause occurs generally during the winter months when ambient temperatures are
      cool and food sources scarce. Whilst the environmental factors involved in
      determining diapause have been known for a long time, the genes and molecular
      events controling its initiation are poorly understood. Here I outline the
      factors that initiate diapause and highlight recent studies that implicate
      insulin signaling in its control.

PMID- 18820433
TI  - Drosophila mechanotransduction--linking proteins and functions.
AB  - The sensation of touch, gravity, and sound all rely on dedicated ion channels
      that transduce mechanical stimulus forces into electrical signals. The functional
      workings and molecular identities of these mechanotransducer channels are little
      understood. Recent work shows that the mechanotransducers for fly and vertebrate
      hearing share equivalent gating mechanisms, whereby this mechanism can be probed
      non-invasively in the mechanics of the Drosophila ear. Here, we describe how this
      mechanics can be used to evaluate the roles of identified proteins in the process
      of mechanosensation and, specifically, their contributions to
      mechanotransduction.

PMID- 18820434
TI  - Curable genetic instability of a gal4 transgene in Drosophila.
AB  - Transgenes, especially those driving production of the GAL4 transcription factor
      in a specific spatial pattern, are a critical and widely used tool in the
      Drosophila research community. We recently noticed loss of GAL4-driven reporter
      gene expression in a series of crosses, and traced that loss of reporter gene
      expression to stochastic physical loss of the GAL4 gene in the driver line. We
      have demonstrated that the instability of the GAL4 transgene can be "cured" by
      treatment of the line with tetracycline, suggesting that the causative agent is
      of bacterial origin. A PCR assay revealed that the line is not infected by
      Wolbachia, an intracellular parasite known to infect a large percentage of stocks
      in the public stock centers and to affect mutant phenotypes. Our data indicate
      that other tetracycline-sensitive agents can cause genetic instability of
      transgenes, and also provides a potential solution to the problem.

PMID- 18820435
TI  - reduced ocelli encodes the leucine rich repeat protein Pray For Elves in
      Drosophila melanogaster.
AB  - The ocelli are three simple photoreceptors on the vertex of the fruit fly head.
      We sought to identify the gene encoded by the classical ocellar mutant, reduced
      ocelli (rdo). Deficiency and inversion breakpoint mapping and P-element induced
      male recombination analyses were performed and Pray For Elves (PFE; CG15151;
      Fbgn0032661) emerged as a promising candidate for the rdo phenotype. The PFE
      locus maps to polytene region 36E on chromosome 2L between elfless (Fbgn0032660)
      and Arrestin 1 (Fbgn0000120). FlyBase annotation predicts that PFE encodes a
      serine/threonine kinase, yet protein prediction programs revealed no kinase
      domain. These analyses suggest that PFE simply encodes a leucine rich repeat
      molecule of unknown function, but presumably functions in nervous system protein
      protein interaction. Two classical spontaneous alleles of rdo, rdo(1) and rdo(2),
      were characterized and the underlying mutations result from a small deletion
      spanning exon 1/intron 1 and a B104/roo insertion into the 3'UTR of PFE,
      respectively. Transposase-mediated excisions of several P-elements inserted into
      the PFE locus revert the rdo phenotype and a full-length PFE cDNA is sufficient
      to rescue rdo. A Gal4 enhancer trap reveals a broad adult neural expression
      pattern for PFE. Our identification and initial characterization of the rdo locus
      will contribute to the understanding of neurogenesis and neural development in
      the simple photoreceptors of the Drosophila visual system.

PMID- 18820436
TI  - Current topics in organogenesis and gametogenesis.
AB  - At the 49(th) Annual Drosophila Research Conference from April 3-8, 2008 in San
      Diego there were eight talks and over ninety posters in the section on
      Organogenesis and Gametogenesis. These covered a wide range of topics within the
      two broad categories of organ-specific stem cells (including germ cells) and
      organ-specific developmental programs. Here we discuss eleven of these
      presentations describing current research into the formation of the gonad,
      intestine, trachea, muscle and leg joint. The new insights presented advance our
      understanding of the molecular events that underlie interactions between stem
      cells and their niches as well as mechanisms underlying tissue-specific
      differentiation programs.

PMID- 18820437
TI  - Advances in age-old questions.
AB  - Drosophila melanogaster is an ideal model organism for various types of aging
      studies. They are easy to maintain, relatively inexpensive, have short life
      cycles, provide large sample sizes, and can be genetically manipulated via
      various methods for testing. The 49(th) Annual Drosophila Research Conference,
      held in San Diego, CA (April 2-6, 2008), had over 30 poster presentations and
      eight platform talks devoted to physiology and aging, and seven presentations in
      a longevity and functional senescence workshop. The data presented via these
      avenues included life span manipulation, physiological related genes, candidate
      aging genes, gene expression, signaling, and using D. melanogaster as a model for
      age related disease, to name a few. This report provides highlights of some of
      the information presented in the poster, platform and workshop presentations.

PMID- 18820438
TI  - Drosophila polymorphism database (DPDB): a portal for nucleotide polymorphism in
      Drosophila.
AB  - As a growing number of haplotypic sequences from resequencing studies are now
      accumulating for Drosophila in the main primary sequence databases, collectively
      they can now be used to describe the general pattern of nucleotide variation
      across species and genes of this genus. The Drosophila Polymorphism Database
      (DPDB) is a secondary database that provides a collection of all well-annotated
      polymorphic sequences in Drosophila together with their associated diversity
      measures and options for reanalysis of the data that greatly facilitate both
      multi-locus and multi-species diversity studies in one of the most important
      groups of model organisms. Here we describe the state-of-the-art of the DPDB
      database and provide a step-by-step guide to all its searching and analytic
      capabilities. Finally, we illustrate its usefulness through selected examples.
      DPDB is freely available at http://dpdb.uab.cat.

PMID- 18820439
TI  - A green fluorescent protein-based reporter for protein nuclear import studies in
      Drosophila cells.
AB  - Green fluorescent protein-based reporters are commonly used to investigate
      protein nucleocytoplasmic transport. In this study we developed a novel reporter
      GFP2-GST which consists of two copies of GFP and one copy of GST, and tested it
      in two commonly used Drosophila cell lines. The size of the GFP2-GST reporter
      exceeds the passive diffusion limit across the nuclear pore complexes. It shows
      an exclusive cytoplasmic localization and displays a restrictive nuclear
      localization when a nuclear localization signal is appended. This reporter will
      largely facilitate the characterization and identification of NLS sequences in
      the fly proteome.

PMID- 18820440
TI  - Stem cells: what can we learn from flies?
AB  - Studies in recent years have resulted in rapid progress in the reprogramming of
      terminally differentiated somatic cells toward their embryonic and pluripotent
      states. These discoveries not only allowed the understanding of the unique
      "stemness" feature of stem cells, but also have been advantageous in bypassing
      the difficult ethical debates on applying embryonic stem cells in biomedical
      research and regenerative medicine. However, most of the strategies to date have
      relied on ectopic expression of a particular set of transcription factors by
      integrating viruses, potentially leading to unexpected mutations and
      tumorigenesis that restrict their clinical applications. A few years ago, germ
      cells were also reported to have the potential to become pluripotent after
      treatment with extrinsic growth factors in cell culture, without the risk of
      mutations in their therapeutic use. The understanding of the germ cell
      differentiation pathway will have significant implications on stem cell biology.
      For over a decade, Drosophila germ cells have emerged as a powerful system used
      to study both the extrinsic and intrinsic factors in a microenvironmental "niche"
      for stem cell self-renewal and differentiation. In addition, other adult fly stem
      cell lineages that mimic human intestinal and haematopoietic stem cells were also
      identified recently. Because of their powerful genetics and relatively short
      lifespan, we anticipate discoveries from flies will provide valuable knowledge to
      unravel the mysteries of stem cells in the coming years.

PMID- 18820441
TI  - Transgenic inhibitors of RNA interference in Drosophila.
AB  - RNA silencing functions as an adaptive antiviral defense in both plants and
      animals. In turn, viruses commonly encode suppressors of RNA silencing, which
      enable them to mount productive infection. These inhibitor proteins may be
      exploited as reagents with which to probe mechanisms and functions of RNA
      silencing pathways. In this report, we describe transgenic Drosophila strains
      that allow inducible expression of the viral RNA silencing inhibitors Flock House
      virus-B2, Nodamura virus-B2, vaccinia virus-E3L, influenza A virus-NS1 and
      tombusvirus P19. Some of these, especially the B2 proteins, are effective
      transgenic inhibitors of double strand RNA-induced gene silencing in flies. On
      the other hand, none of them is effective against the Drosophila microRNA
      pathway. Their functional selectivity makes these viral silencing proteins useful
      reagents with which to study biological functions of the Drosophila RNA
      interference pathway.

PMID- 18820442
TI  - Par-1 and PP2A: Yin-Yang of Bazooka localization.
AB  - Apical basal cell polarity is a fundamental feature of all epithelial cells.
      Identification of the genes involved in the polarization of epithelial cells has
      begun to reveal the mechanisms underlying the establishment and maintenance of
      cell polarity. An important issue is to understand the molecular basis for
      localization of cell polarity proteins in the context of the developing organism.
      Bazooka (Baz, Drosophila homolog of Par-3) plays a crucial role in organizing
      cell polarity in several different tissues. In the ovarian follicle epithelium,
      Par-1 protein kinase regulates Baz localization to the apical cell cortex by
      excluding phosphorylated Baz from the lateral region. In photoreceptor cells of
      retinal epithelium, Baz is targeted to the adherens junction (AJ) instead of the
      apical domain. Our study suggests that in photoreceptors, Par-1 blocks the
      localization of Baz to AJ whereas protein phosphatase 2A (PP2A) promotes Baz
      localization by antagonizing the Par-1 effects. In this extra view, we provide a
      brief overview and perspective of our findings on the antagonistic function of
      Par-1 and PP2A in Baz localization during photoreceptor morphogenesis.

PMID- 18820443
TI  - Flow cytometry and karyotype analysis of D.melanogaster eye disc cells.
AB  - The developing Drosophila eye-antennal disc is a particularly suited system for
      the genetic and cellular studies of complex biological processes. Methods to
      analyze Drosophila eye discs by flow cytometry are mainly based on the
      dissociation of tissues with trypsin. Dissociation operated by trypsin is very
      effective, though it causes a lot of stress to live cells often compromising the
      use of treated cells for further analyses. Here, we report a method to produce
      dissociated eye-disc cells that retain cell-membrane markers and that can be used
      for flow cytometry and cytological analysis of mitotic chromosomes. The method
      described is a great complementing tool for the cellular characterization of
      phenotypes resulting from classic clonal and miss-expression approaches in the
      Drosophila eye.

PMID- 18820444
TI  - Combined rather than separate pathways for hedonic and sensory aspects of taste
      in fly larvae?
AB  - In mammals, the hedonic aspects (good versus bad) and sensory aspects (i.e., the
      molecular quality) of taste are associated with different brain regions.
      Anatomical data argue against such a separation in the primary taste center of
      Drosophila larvae. Is only one aspect of taste represented or do both co-exist at
      the same location? I present evidence for a hedonic representation in the larval
      taste center and review anatomical and behavioral data which support the co
      existence of a sensory representation of taste with a hedonic representation.

PMID- 18820445
TI  - Cut mutant Drosophila auditory organs differentiate abnormally and degenerate.
AB  - The Drosophila antenna is a sophisticated structure that functions in both
      olfaction and audition. Previous studies have identified Homothorax,
      Extradenticle, and Distal-less, three homeodomain transcription factors, as
      required for specification of antennal identity. Antennal expression of cut is
      activated by Homothorax and Extradenticle, and repressed by Distal-less. cut
      encodes the Drosophila homolog of human CAAT-displacement protein, a cell cycle
      regulated homeodomain transcription factor. Cut is required for normal
      development of external mechanosensory structures and Malphigian tubules (kidney
      analogs). The role of cut in the Drosophila auditory organ, Johnston's organ, has
      not been characterized. We have employed the FLP/FRT system to generate cut null
      clones in developing Johnston's organ. In cut mutants, the scolopidial subunits
      that constitute Johnston's organ differentiate abnormally and subsequently
      degenerate. Electrophysiological experiments confirm that adult Drosophila with
      cut null antennae are deaf. We find that cut acts in parallel to atonal, spalt
      major, and spalt-related, which encode other transcription factors required for
      Johnston's organ differentiation. We speculate that Cut functions in conjunction
      with these factors to regulate transcription of as yet unidentified targets.

PMID- 18820446
TI  - Cytological investigation of the mechanism of parthenogenesis in Drosophila
      mercatorum.
AB  - Thelytokous parthenogenesis (female progeny only) in animals is believed to arise
      initially in unfertilized eggs produced by bisexual females via the fusion of two
      haploid nuclei following meiosis, to produce diploid female progeny. The
      transition from sexual to parthenogenetic mechanisms of reproduction requires
      that the egg replace the paternal contributions of a haploid genetic complement
      and the basal body, which is thought to be essential for centrosome formation.
      The transitional facultative parthenogenetic stage is usually associated with a
      high rate of failed or abortive development, but the molecular and mechanistic
      reasons for this failure remain unclear. We show that a facultative
      parthenogenetic strain of Drosophila mercatorum produces a high percentage of
      unfertilized eggs competent to restore diploidy and form centrosomes de novo
      following meiosis. The female meiotic products replicate and divide by an
      acentrosomal mechanism in most oocytes and cytoplasmic centrosomes form in 35% of
      the oocytes. However, after pronuclear replication the cytoplasmic centrosomes
      must "capture" two haploid nuclei in order to restore diploidy. In practice, this
      process frequently fails due to centrosome-mediated capture events of single or
      more than two haploid nuclei, as well as multiple nuclear capture events in a
      single embryo when excess free centrosomes are not inactivated following
      formation of the first zygotic nucleus. Additionally, as development proceeds,
      many of the centrosomes that initiate syncytial development do not remain
      functional, possibly due to centrosome maturation defects, and later stages of
      syncytial development fail. The combined effect of the high error rate associated
      with nuclear capture and the failure of centrosome maturation during later
      developmental prevents successful parthenogenesis in most of the eggs that
      initiate development. This shows that the high rate of failed development
      associated with the transition from sexual to parthenogenetic reproduction is
      limited by the low probability of the formation of a diploid zygotic nucleus with
      the correct complement of centrosomes in D. mercatorum.

PMID- 18820447
TI  - Direct measurement of the performance of the Drosophila jump muscle in whole
      flies.
AB  - We have developed a novel apparatus, an ergometer, to simultaneously measure the
      horizontal and vertical components of the work done during takeoff by the
      fruitfly, Drosophila. We confirm the anatomical prediction that all the work
      comes from the middle (mesothoracic) legs. With all six legs on the ergometer
      platform, displacement is directed roughly 45 degrees forwards or backwards. Both
      directions are equally likely. This provides for a random, rapid horizontal
      component to the escape behaviour for flies. When the thoracic stiffness is
      reduced (due to a mutation in which the indirect flight muscles (IFM) do not form
      myofibrils), jump output is increased. We conclude that the jump muscle, the
      tergal depressor of trochanter (TDT), which lacks direct muscle antagonists,
      performs work during the jump against thoracic stiffness. Both cuticle and IFM
      contribute to the thoracic stiffness as the TDT still produces repeated
      contractions in the absence of the IFM. Degeneration of the TDT due to mutants in
      three sarcomeric proteins results in reduction of the jump output. In one of
      these, the myosin heavy chain mutant, Mhc5, we show that degeneration occurs with
      age. The anatomical characteristics of Drosophila mean that we are recording, for
      the first time in the intact fly, the output of a single muscle that has high
      homology to vertebrate skeletal muscle. Developing an ergometer for Drosophila
      offers novel opportunities to assess the functional consequences of mutations in
      muscle proteins, synaptic physiology, neuromuscular development and aging.

PMID- 18820448
TI  - Imp (IGF-II mRNA-binding protein) is expressed  during spermatogenesis in
      Drosophila melanogaster.
AB  - Drosophila spermatogenesis results in the production of sixty-four ~2-mm
      spermatozoa from an individual founder cell. Little is known, however, about the
      elongation of spermatids to such an extraordinary length. In a partial screen of
      a GFP-tagged protein trap collection, four insertions were uncovered that exhibit
      expression toward the tail ends of spermatid cysts and within the apical tip of
      the testis, suggesting that these protein traps may represent genes involved in
      spermatid elongation and pre-meiotic spermatogenesis, respectively. Inverse PCR
      followed by cycle sequencing and BLAST revealed that all four protein traps
      represent insertions within Imp (IGF-IImRNA binding protein), a known
      translational regulator. Testis enhancer trap analysis also reveals Imp
      expression in the cells of the apical tip, suggesting transcription of Imp prior
      to the primary spermatocyte stage. Taken together, these results suggest a role
      for Imp in the male germline during both spermatid elongation and premeiotic
      spermatogenesis.

PMID- 18820449
TI  - Visual edge orientation shapes free-flight behavior in Drosophila.
AB  - Insects rely on visual cues to estimate and control their distance to approaching
      objects and their flight speed. Here we show that in free-flight, the motion cues
      generated by high-contrast vertical edges are crucial for these estimates. Within
      a visual environment dominated by high-contrast horizontal edges, flies fly
      unusually fast and barely avoid colliding with the walls of the enclosure. The
      disruption of flight behavior by horizontal edges provides insight into the
      structure of visually-mediated control algorithms.

PMID- 18820450
TI  - Cell cycle regulation.
AB  - Drosophila researchers met in sunny San Diego for the 49(th) Annual Meeting of
      The Genetics Society of America. It was cold outside and even colder inside. Like
      last year, 'Mitosis, Meiosis and Cell Division' was no longer a session. Instead,
      we searched out and covered talks and posters in 'Cell Division and Growth
      Control', 'Gametogenesis', 'Cytoskeleton and Cell Biology' and 'Genome and
      Chromosome Structure'. We split up for maximal coverage and re-grouped later for
      the Workshop on Cell Cycle and Checkpoints. We apologize in advance for the
      brevity or omission of some reports.

PMID- 18820451
TI  - New advances in stem cell biology: A perspective from gametogenesis.
AB  - Regeneration of adult tissues relies on a small population of adult stem cells
      located in a specialized microenvironment. The adult stem cells divide
      continuously to produce new stem cells, as well as differentiated daughter cells
      to replenish lost cells due to damage or aging. The molecular mechanisms
      controlling their ability to divide, self-renew and differentiate remain largely
      undiscovered. The Drosophila reproductive systems have proven to be excellent
      models to understand the basic mechanisms regulating stem cell function. This
      report summarizes some of the recent advances in this field that were presented
      at the 49(th) Drosophila Research Conference held in San Diego in April 2008.

PMID- 18820452
TI  - Distinct signaling of Drosophila Activin/TGF-beta family members.
AB  - Growth factors of the TGF-beta family signal through type I/II receptor complexes
      that phosphorylate SMAD transcription factors. In this study, we analyzed
      signaling of all seven TGF-beta members to identify those that mediate growth
      through the Drosophila type I receptor BABO. We find that two potential ligands
      of BABO, Myoglianin (MYO) and Maverick (MAV), do not activate dSMAD2. Only
      Drosophila Activin (dACT) and the Activin-like ligand Dawdle (DAW) signal through
      BABO in combination with the type II receptor PUNT and activate dSMAD2.
      Surprisingly, we find that activation of BABO can also lead to the
      phosphorylation of the "BMP-specific" MAD. In wing discs, expression of an
      activated form of dSMAD2 promotes growth similar to dACT and activated BABO. By
      itself, activated dSMAD2 does not affect DPP/GBB target genes. However,
      coexpression of activated forms of dSMAD2 and MAD additively induces the
      expression of spalt. In contrast to dACT, we find that DAW does not promote
      growth when expressed in wings. In fact, coexpression of DAW with MAD or dSMAD2
      decreases growth. daw mutants die primarily during larval stages and exhibit anal
      pad phenotypes reminiscent of babo mutants. The rescue of daw mutants by
      restricted expression in neuroendocrine cells indicates that Activin-type ligands
      are likely distributed through the endocrine system. The distinct signaling of
      dACT, DAW and MYO through BABO suggests the existence of co-receptors that
      modulate the canonical SMAD pathway.

PMID- 18820453
TI  - Heterochromatin: not just for silencing anymore: report of the Eighth
      International Conference on Drosophila Heterochromatin.

PMID- 18820454
TI  - Life is a gas.

PMID- 18820455
TI  - CYLD: a multifunctional deubiquitinase.
AB  - The nuclear factor-kappaB (NF-kappaB) and c-Jun NH2-terminal kinase (JNK)
      signaling pathways regulate diverse biological processes, including the immune
      and inflammatory response, cell growth, apoptosis, and tumour formation. Not
      surprisingly therefore defects to either pathway contributes to the progression
      of numerous human disorders. Enhancing our understanding of the mechanisms that
      control signaling through these pathways is therefore significant as it may
      enable development of specific treatments. In this regard, CYLD was recently
      identified as a negative regulator of NF-kappaB and JNK signaling. CYLD has a C
      terminal catalytic domain characteristic of deubiquitinating enzymes, and this is
      essential for CYLD to remove ubiquitin from certain proteins that positively
      mediate signaling through the NF-kappaB and JNK pathways. Recent studies have
      revealed a requirement for CYLD in many different processes and have provided
      some insight into the underlying mechanisms.

PMID- 18820456
TI  - Between transcription and translation: Re-defining RNA and regulation.
AB  - The diverse functional roles for RNA molecules in cells of the developing embryo
      have been an area of intense study in the last few years. Progress reported at
      the 49(th) Annual Drosophila Research Conference in San Diego, California
      highlighted many of the varied mechanistic activities for RNAs. In particular,
      talks at the 'RNA Biology' platform session provided a great deal of insight into
      the function of RNA transcripts and their associated protein complexes. The
      topics covered included: (1) a large-scale screen examining the localization of
      mRNAs during embryonic development, (2) mechanisms of mRNA transport in different
      cell types, (3) localization-dependent repression of mRNA translation and (4) the
      activity of the RNAi machinery in insulator-mediated chromatin structures. Our
      journey through the modern RNA world clearly indicates that we should be
      considering a much more expansive role for RNAs in molecular biology.

PMID- 18820457
TI  - Drosophila klaroid encodes a SUN domain protein required for Klarsicht
      localization to the nuclear envelope and nuclear migration in the eye.
AB  - KASH (Klarsicht/Anc-1/Syne homology) domain proteins are cytoskeleton-associated
      proteins localized uniquely to the outer nuclear membrane. Klarsicht is a KASH
      protein required for nuclear migration in differentiating cells of the Drosophila
      eye. The C-terminal KASH domain of Klarsicht resides in the perinuclear space,
      and the cytoplasmic moiety connects to the microtubule organizing center. In C.
      elegans and vertebrate cells, SUN (Sad1/UNC-84) domain proteins reside in the
      inner nuclear membrane and tether KASH proteins to the outer nuclear membrane. Is
      there a Drosophila SUN protein that performs a similar function, and if so, is it
      like Klarsicht, obviously essential for nuclear positioning only in the eye?
      Here, we identify Drosophila Klaroid, a SUN protein that tethers Klarsicht.
      klaroid loss-of-function mutants are indistinguishable phenotypically from
      klarsicht mutants. Remarkably, neither gene is essential for Drosophila viability
      or fertility, and even in klaroid klorsicht double mutants, the only obvious
      external morphological defect is rough eyes. In addition, we find that klaroid
      and klarsicht are required for nuclear migration in differentiating neurons and
      in non-neural cells. Finally, while perinuclear Klaroid is ubiquitous in the eye,
      Klarsicht expression is limited to differentiating cells and may be part of the
      trigger for apical nuclear migration.

PMID- 18820458
TI  - A protein nuclear extract from D. melanogaster larval tissues.
AB  - Preparation of protein nuclear extracts is often the first step to study in vitro
      biological processes occurring in the nucleus of the eukaryotic cell. Nuclear
      extracts have been extensively used in different model organisms to identify and
      study protein function in nuclei. Drosophila embryos can be collected in large
      quantities and have been the source of choice for the production of protein
      nuclear extracts. However, most of Drosophila in vivo studies on protein function
      are conducted in larval tissues. Here we report a new method to produce highly
      stable large-scale protein nuclear extracts from whole Drosophila larvae that are
      suited for a variety of biochemical analyses.

PMID- 18820459
TI  - A genomic response to the yeast transcription factor GAL4 in Drosophila.
AB  - The yeast transcription factor GAL4 is widely used in Drosophila genetics to
      misexpress genes that are under control of the yeast upstream activator sequence
      (UAS). Here we show that high levels of GAL4 change the expression of many
      Drosophila genes in a UAS-independent manner, including genes that encode
      components of important signaling pathways. We find that at least part of the
      genomic response to GAL4 appears to be caused by effects of GAL4 on stress and
      immune response pathways. Finally, using the transcription factor Senseless as an
      example, we demonstrate how an interaction between GAL4 and a GAL4-driven protein
      can impede the use of the GAL4/UAS system in experiments aimed at determining the
      transcriptional response to a misexpressed gene.

PMID- 18820460
TI  - Genome and chromosome structure: Twelve dynamic and evolving genomes.
AB  - Chromosomes are not inert structures that haul the genome through cell division.
      The dynamic properties of chromosomes, during the cell cycle, the lifetime of the
      organism and across evolutionary time, featured prominently at the 49(th) Annual
      Drosophila Research Conference. Platform presentations, workshops and posters
      focused on many aspects of chromosome structure and function including chromosome
      interactions such as trans-silencing and pairing between homologous and non
      homologous chromosomes, specialized portions of the chromosome including the
      centromere and telomeres, the structure, function and evolution of the large
      heterochromatic domains such as the Y and 4(th) chromosomes, centric
      heterochromatin and subtelomeric heterochromatin. The speed of evolutionary
      changes in these regions, and the consequences for speciation and hybrid
      incompatibility, were recurring themes. Finally, there was considerable new
      insight offered into the mechanics by which chromosomes are rearranged and
      changes in the types of alterations occurring over the lifetime of the organism,
      which can result in novel genes and gene flow between chromosomes. The
      availability of the twelve sequenced Drosophila genomes has allowed new insights
      into the structure, function and evolutionary transformation of chromosomes and
      genomes that will continue to transform our view of the chromosome as a dynamic
      and flexible entity that houses and regulates the genome.

PMID- 18820461
TI  - Advances in microRNA biology.

PMID- 18820462
TI  - An eGFP-based genetic screen for defects in light-triggered subcelluar 
      translocation of the Drosophila photoreceptor channel TRPL.
AB  - Signaling at the plasma membrane is modulated by up- and downregulation of
      signaling proteins. A prominent example for this type of regulation is the
      Drosophila TRPL ion channel that changes its spatial distribution within the
      photoreceptor cell. In dark-raised flies TRPL is localized in the rhabdomeral
      photoreceptor membrane and it translocates to the cell body upon illumination. It
      has been shown that TRPL translocation depends on the activation of the
      phototransduction cascade and requires the presence of functional rhodopsin as
      well as Ca2+-influx through a second lightactivated ion channel, TRP. However,
      little is known about the cell biological mechanism underlying TRPL
      translocation. Here we describe a FRT/FLP screen designed to isolate mutants
      defective in TRPL internalization based on the localization of eGFP-tagged TRPL
      in the eyes of living flies. We mutated chromosome arms 2L, 2R and 3R and
      isolated 12 mutants that failed to internalize TRPL. We found that four mutants
      did not complement genes known to affect TRPL translocation, which are trp, ninaE
      and inaD. Two of the isolated mutants represent new alleles of trp and ninaE. The
      trp allele contains a premature stop codon after amino acid 884, whereas the
      ninaE allele has a mutation resulting in the substitution P193S. As determined
      biochemically no TRP or rhodopsin protein, respectively, was expressed in the
      eyes of these mutants. The absence of TRP or rhodopsin in the isolated mutants
      readily explains the defect in TRPL internalization and proves the feasibility of
      our genetic screen.

PMID- 18820463
TI  - Downstream of homeotic genes: in the heart of Hox function.
AB  - A functional organ is constituted of diverse cell types. Each one occupies a
      distinct position and is associated to specific morphological and physiological
      functions. The identification of the genetic programs controlling these
      elaborated and highly precise features of organogenesis is crucial to understand
      how a mature organ works under normal conditions, and how pathologies can
      develop. Recently, a number of studies have reported a critical role for Hox
      genes in one example of organogenesis: cardiogenesis in Drosophila. Beyond the
      interest in understanding the molecular basis of functional cardiogenesis, this
      system might provide a model for proposing new paradigms of how Hox genes achieve
      their action throughout development.

PMID- 18820464
TI  - Flies at the farm: Drosophila at Janelia.
AB  - On August 1, 2006 the Howard Hughes Medical Institute's first stand-alone
      research campus opened at Janelia Farm, near Washington DC. Our mission at
      Janelia is to do exceptional fundamental research. Our two scientific foci are to
      understand the function of neural circuits and to develop synergistic imaging
      technologies. To achieve this we have changed many of the conventions of academic
      and/or industrial science. The founding director at Janelia is the well-known
      Drosophilist Gerry Rubin, who has been a central figure in fly molecular,
      developmental and genomic biology in recent decades. Not coincidentally, we at
      Janelia fully appreciate the potential of flies to contribute to an understanding
      of neuronal circuits. Our objectives are ambitious, and in the first ten months
      of operations at Janelia we have made some good beginnings.

PMID- 18820465
TI  - A germline clone screen for meiotic mutants in Drosophila melanogaster.
AB  - Using an FLP/FRT-based method to create germline clones, we screened Drosophila
      chromosome arms 2L and 3R for new female meiotic mutants. The screen was designed
      to recover mutants with severe effects on meiotic exchange and/or segregation.
      This screen yielded 11 new mutants, including six alleles of previously known
      meiotic genes (c(2)M and ald/mps1). The remaining five mutants appear to define
      at least four new genes whose ablation results in severe meiotic defects. Three
      of the novel meiotic mutants were identified at the molecular level. Two of
      these, mcm5(A7) and trem(F9), define roles in meiotic recombination, while a
      third, cona(A12), is important for synaptonemal complex assembly. Surprisingly,
      five of the nine mutants for which the lesion has been identified at the
      molecular level are not the result of mutations characteristic of EMS
      mutagenesis, but rather due to the insertion of the transposable element Doc.
      This study demonstrates the utility of germline clone-based screens for the
      discovery of strong meiotic mutants, including mutations in essential genes, and
      the use of molecular genetic techniques to map the loci.

PMID- 18820466
TI  - Drosophila telomeres: A variation on the telomerase theme.
AB  - In Drosophila, the role of telomerase is carried out by three specialized
      retrotransposable elements, HeT-A, TART and TAHRE. Telomeres contain long tandem
      head-to-tail arrays of these elements. Within each array, the three elements
      occur in random, but polarized, order. Some are truncated at the 5' end, giving
      the telomere an enriched content of the large 3' untranslated regions, which
      distinguish these telomeric elements from other retrotransposons. Thus,
      Drosophila telomeres resemble other telomeres because they are long arrays of
      repeated sequences, albeit more irregular arrays than those produced by
      telomerase. The telomeric retrotransposons are reverse-transcribed directly onto
      the end of the chromosome, extending the end by successive transpositions. Their
      transposition uses exactly the same method by which telomerase extends chromosome
      ends--copying an RNA template. In addition to these similarities in structure and
      maintenance, Drosophila telomeres have strong functional similarities to other
      telomeres and, as variants, provide an important model for understanding general
      principles of telomere function and evolution.

PMID- 18820467
TI  - Climatic adaptations of body melanisation in Drosophila melanogaster from Western
      Himalayas.
AB  - We investigated population divergence in body melanisation in wild samples of
      Drosophila melanogaster across an elevational gradient (512-2202 m) in the
      Western Himalayas. Wild populations are characterized by higher phenotypic
      variability as compared with laboratory populations. Significant differences in
      elevational slope values for three posterior abdominal segments (fifth, sixth and
      seventh) in wild versus laboratory populations suggest plastic effects. However,
      elevational slope values do not differ for the three anterior abdominal segments
      (second, third and fourth). Thus, elevational changes in melanisation include
      genetic as well as plastic effects. Fitness consequences of within population
      variability were analyzed on the basis of assorted darker and lighter flies from
      two highlands as well as from two lowland localities. There is lack of
      correlation of melanisation with body size as well as ovariole number in assorted
      darker and lighter flies. For each population, darker flies showed higher
      desiccation resistance, lower rate of water loss, longer copulation duration and
      greater fecundity as compared with lighter flies. Phenotypic variations in body
      melanisation can be interpreted in relation with seasonal changes in temperature
      as well as humidity (Tcv and RHcv) of the sites of origin of populations. Thus,
      elevational changes in body melanisation may represent genetic response to
      selection pressures imposed by colder and drier climatic conditions in the
      Western Himalayas.

PMID- 18820468
TI  - Mutation of the gene encoding the ubiquitin activating enzyme ubal causes tissue
      overgrowth in Drosophila.
AB  - Protein ubiquitination has been shown to regulate a wide variety of cellular
      process including cell cycle progression, protein trafficking and apoptosis. Most
      regulation of ubiquitination occurs at the level of E2 or E3 enzymes and their
      interactions with specific substrates. In a screen for mutations that cause
      tissue overgrowth, we recovered multiple mutations in the Drosophila Uba1 gene
      that encodes the E1 enzyme that is required for the first step of most, if not
      all, ubiquitination reactions. Previous studies with yeast and mammalian cells
      have shown that disrupting E1 function results in a cell-cycle arrest. Here we
      show that in the developing Drosophila eye, clones of cells that are homozygous
      for partial loss of function alleles of Uba1 show defects in apoptosis. Moreover,
      clones homozygous for stronger or complete loss of function alleles of Uba1, that
      are predicted to have a global defect on ubiquitination, survive poorly but are
      able to stimulate the overgrowth of adjacent wild-type tissue. Experiments with
      mammalian cells show that reducing the level of RNA of the mammalian Uba1
      ortholog, UBE1, also results in increased expression of specific growth factor
      genes. Our studies show that a reduction in E1 activity can promote tissue growth
      in a multicellular organism and raise the possibility that changes in E1 activity
      may occur during normal development or in cancer.

PMID- 18820469
TI  - Recent efforts to model human diseases in vivo in Drosophila.
AB  - Upon completion of sequencing the Drosophila genome, it was estimated that 61% of
      human disease-associated genes had sequence homologs in flies, and in some
      diseases such as cancer, the number was as high as 68%. We now know that as many
      as 75% of the genes associated with genetic disease have counterparts in
      Drosophila. Using better tools for mutation detection, association studies and
      whole genome analysis the number of human genes associated with genetic disease
      is steadily increasing. These detection efforts are outpacing the ability to
      assign function and understand the underlying cause of the disease at the
      molecular level. Drosophila models can therefore advance human disease research
      in a number of ways by: establishing the normal role of these gene products
      during development, elucidating the mechanism underlying disease pathology, and
      even identifying candidate therapeutic agents for the treatment of human disease.
      At the 49(th) Annual Drosophila Research Conference in San Diego this year, a
      number of labs presented their exciting findings on Drosophila models of human
      disease in both platform presentations and poster sessions. Here we can only
      briefly review some of these developments, and we apologize that we do not have
      the time or space to review all of the findings presented which use Drosophila to
      understand human disease etiology.

PMID- 18820470
TI  - Accentuate the negative: proteome comparisons using the negative proteome
      database.
AB  - The availability of complete genome sequence information for diverse organisms
      including model genetic organisms has ushered in a new era of protein sequence
      comparisons making it possible to search for commonalities among entire proteomes
      using the Basic Local Alignment Search Tool (BLAST). Although the identification
      and analysis of proteins shared by humans and model organisms has proven an
      invaluable tool to understanding gene function, the sets of proteins unique to a
      given model organism's proteome have remained largely unexplored. We have
      constructed a searchable database that allows biologists to identify proteins
      unique to a given proteome. The Negative Proteome Database (NPD) is populated
      with pair-wise protein sequence comparisons between each of the following
      proteomes: Homo sapiens, Mus musculus, Drosophila melanogaster, Caenorhabditis
      elegans, Saccharomyces cerevisiae, Dictyostelium discoideum, Chlamydomonus
      reinhardti, Escherichia coli K12, Arabidopsis thaliana and Methanoscarcina
      acetivorans. Our analysis of negative proteome datasets using the NPD has thus
      far revealed 107 proteins in humans that may be involved in motile cilia
      function, 1628 potential pesticide target proteins in flies, 659 proteins shared
      by flies and humans that are not represented in the less neurologically complex
      worm proteome, and 180 nuclear encoded human disease associated proteins that are
      absent from the fly proteome. The NPD is the only online resource where users can
      quickly perform complex negative and positive comparisons of model organism
      proteomes. We anticipate that the NPD and the adaptable algorithm which can
      readily be used to duplicate this analysis on custom sets of proteomes will be an
      invaluable tool in the investigation of organism specific protein sets.

PMID- 18820471
TI  - The generation and analysis of deficiencies within a small genomic region on the
      X chromosome of Drosophila melanogaster containing two genes, enhancer of
      rudimentary and CG15352.
AB  - The enhancer of rudimentary gene, e(r), encodes a 104-amino-acid, highly
      conserved transcription cofactor. Hypomorphic mutations of e(r) show an
      enhancement of a hypomorphic rudimentary mutant wing phenotype. These mutants in
      a wild-type background are viable, fertile, and morphologically wild-type. Since
      the only mutant alleles were hypomorphic, it was important to isolate null
      mutations to determine if any other phenotypes might be associated with a loss-of
      function of e(r). We utilized a marked P element, P{SUPor-P, y(+)}, located 895
      bp upstream of the start of transcription of e(r) to generate nineteen
      deficiencies in the region. Deficiencies of e(r) enhance the mutant wing
      phenotype of a hypomorphic rudimentary allele, r(hd1). In a wild-type background,
      the deficiencies of e(r), unlike the hypomorphic alleles, have a low viability
      and females have low fertility. The expression of e(r) in the nurse cells of the
      ovary is consistent with the low fertility, and suggests an ovarian function for
      e(r). Deficiencies of CG15352, the gene directly upstream of e(r), are not
      associated with any obvious mutant phenotypes and present the possibility that it
      encodes a nonvital or redundant function.

PMID- 18820472
TI  - Modulation of MAPK activities during egg activation in Drosophila.
AB  - The mitogen-activated protein kinases (MAPKs) play essential roles during oocyte
      maturation and egg activation and are also active in somatic cell cycle
      regulation in many animals. In clams, starfish, ascidians, mice, and frogs, the
      species-specific timing of MAPK activity during oocyte maturation and egg
      activation correlates with the different meiotic arrest points of these various
      organisms. Furthermore, MAPKs have been shown to regulate the meiotic cell cycle
      in marine invertebrates and vertebrates. The initial trigger for egg activation
      in insects is different from that of marine invertebrates and vertebrates, and it
      was not previously known whether changes in MAPK activity accompany egg
      activation in insects. To examine the regulation of MAPKs during Drosophila egg
      activation and early embryogenesis, we quantified the levels of phosphorylated
      (active) forms of ERK, p38 and JNK by western blotting with antibodies specific
      to the phospho-forms of these kinases. Levels of phospho-ERK, phospho-p38 and
      phospho-JNK are high in Drosophila oocytes. Upon egg activation, levels of all
      these phospho- (active) forms of MAPKs decrease. Fertilization is not required
      for this decrease, consistent with the independence of egg activation from
      fertilization in Drosophila. The decrease in levels of phospho-MAPK occurs
      normally in embryos laid by sterile females mutant in the egg activation genes
      cortex, sarah, and prage. We present a model in which the decrease in MAPK
      activity is an intermediate step in the pathway leading from the calcium signal
      that initiates egg activation to the downstream events of activation.

PMID- 18820473
TI  - Epigenetics: More than genetics.

PMID- 18820474
TI  - Fruit flies like a (rotten) banana.

PMID- 18820475
TI  - Differential expression of Dystroglycan-spliceforms with and without the mucin
      like domain during Drosophila embryogenesis.
AB  - Dystroglycan (DG) is a widely expressed extracellular matrix (ECM) receptor
      required for muscle viability, synaptogenesis, basement-membrane formation and
      epithelial development. As an integral component of the Dystrophin-associated
      glycoprotein complex, DG plays a central role in linking the ECM and the
      cytoskeleton. Disruption of this linkage in skeletal muscle is the underlying
      cause in various types of muscular dystrophies (MD). One particular type of MD is
      caused by alterations of O-linked glycosylation in the mucin-like domain of DG,
      which is required for binding of the ECM molecules Laminin and Perlecan. In
      epithelial cells, reduced expression of DG is associated with increased
      invasiveness of cancer cells and loss of cell polarity. Drosophila Dg is, in
      contrast to vertebrate Dg, subjected to differential splicing of the mRNA.
      Interestingly, the shorter DG splice forms lack the mucin-like domain. Here, we
      describe the embryonic expression patterns of full-length DG and a short variant
      of DG. We find that differential splicing of Dg is developmentally regulated and
      tissue-specific. In some tissues, e.g., hindgut, midgut constrictions, gonads,
      both DG variants can be detected. For the long form, we detected specific
      expression at the blastoderm stage, in the epidermis and in the tracheal pits.
      The short form showed exclusive expression in dorsal vessel cells, chordotonal
      organs and dorsal median cells. In the nervous system, the long form is
      predominantly expressed on axons, while the short form is present on glial cells.
      Our findings further support the idea that DG forms lacking the mucin-like domain
      serve a specific function in Drosophila.

PMID- 18820476
TI  - Pipeline for acquisition of quantitative data on segmentation gene expression
      from confocal images.
AB  - We describe a data pipeline developed to extract the quantitative data on
      segmentation gene expression from confocal images of gene expression patterns in
      Drosophila. The pipeline consists of five steps: image segmentation, background
      removal, temporal characterization of an embryo, data registration and data
      averaging. This pipeline was successfully applied to obtain quantitative gene
      expression data at cellular resolution in space and at the 6.5-minute resolution
      in time, as well as to construct a spatiotemporal atlas of segmentation gene
      expression. Each data pipeline step can be easily adapted to process a wide range
      of images of gene expression patterns.

PMID- 18820477
TI  - Host immune response and differential survival of the sexes in Drosophila.
AB  - Innate immunity is essential for the survival of organisms across the
      evolutionary spectrum. Drosophila is well studied as a model of innate immunity
      and has been instrumental in establishing principles of defense and gene
      signaling pathways that are shared with humans. Previous studies in Drosophila
      have not focused on differences between the sexes, and in this report we present
      evidence that it is essential to include differences between the sexes. Survival
      rates post-infection, after a fungal or bacterial infection, varied according to
      the combination of signaling pathway (Toll and Imd) and sex tested. We also found
      that antimicrobial protein gene mRNA levels for Drosomycin and Metchnikowin
      showed both similarities and differences between the sexes. These studies
      highlight the need to include both sexes in studies of immune function as well as
      the associated opportunities for advancing our understanding of immunity.

PMID- 18820478
TI  - The Drosophila KASH domain proteins Msp-300 and Klarsicht and the SUN domain
      protein Klaroid have no essential function during oogenesis.
AB  - Proteins harboring a C-terminal KASH (Klarsicht/Anc-1/Syne Homology) domain,
      which attaches to the nucleus, have been identified in many different organisms.
      Two KASH proteins are known from Drosophila, Msp-300 and Klarsicht, the latter of
      which plays a role in nuclear migration during eye development. Here, we show
      that a complete deletion of Msp-300 leads to larval lethality. This lethality
      appears to be due to Msp-300 isoforms containing the N-terminal actin binding,
      but not the C-terminal KASH domain. Msp-300 and Klar are expressed during
      oogenesis and localize to the nuclear envelope of the germ line nuclei. However,
      neither Msp-300 single mutants nor Msp-300; klar double mutants cause defects in
      nuclear migration or anchoring during oogenesis. Germ line nuclear envelope
      localization of both KASH domain proteins depends on klaroid, the only Drosophila
      SUN domain homolog expressed in females. Like Msp-300 and klar, klaroid is also
      dispensable for normal ovarian development.

PMID- 18820479
TI  - Advances in pattern formation: Signaling and transcription.
AB  - The 49(th) Annual Drosophila Research Conference was held in the sunny confines
      of San Diego. As usual, large numbers of Drosophila scientists working in fields
      as different as immunology and evolution descended on the venue. The meeting
      showed that the fly community is still vibrant and diverse even with the funding
      crunch at the NIH and the renewed rumors that Drosophila may have outlived its
      usefulness. This short review will focus on one session of platform presentations
      detailing the recent advances in the field of pattern formation. This session
      offered a variety of topics reviewing the formation of pattern in various tissues
      through diverse mechanisms. I will focus on early embryonic patterning through
      pair-rule genes, specificity of FGF signaling, and tissue regeneration.

PMID- 18820480
TI  - Smiling Gurken gradient: An expansion of the Gurken gradient.
AB  - Morphogen gradients provide unique positional information within a tissue. Cells
      that are sensitive to the concentration of the morphogen integrate this signal
      and develop an appropriately distinct cell fate. A morphogen gradient is usually
      generated by a restricted source and shaped by the speed of diffusion and
      stability of the signaling molecule. In addition, the availability of receptor
      and Heparan Sulfate Proteoglycans (HSPGs) help to shape the gradient. We have
      shown that overexpression of Dally-like protein (Dlp) causes an expansion of
      Gurken distribution and a loss of cell fates which are specified by high levels
      of epidermal growth factor receptor (Egfr) signaling. In this article, we discuss
      how D-Cbl mediated Egfr endocytosis and the levels of Dlp affect the shape of the
      Gurken gradient.

PMID- 18820481
TI  - Recent developments in targeted transgene expression systems.

PMID- 18820482
TI  - On the roles of the Drosophila KASH domain proteins Msp-300 and Klarsicht.
AB  - KASH (Klarsicht, Anc-1, Syne-1 homology) domain-containing proteins anchor the
      nucleus to the actin cytoskeleton or to microtubules. KASH proteins thus play
      pivotal roles in a variety of developmental processes where nuclear positioning
      is critical. Two KASH proteins have been identified in Drosophila: Muscle
      specific protein-300 (Msp-300) and Klarsicht (Klar). Msp-300 anchors nuclei to
      actin, and has been reported to be essential for positioning of nurse cell nuclei
      during oogenesis, and thus production of mature ooctyes. Klar is required for
      positioning of photoreceptor and cone cell nuclei in the developing eye, which is
      critical for proper eye morphology. Here, we asked whether KASH domain-containing
      forms of Msp-300 are required for nuclear positioning in the eye, and we found
      that they are not. Moreover, in the course of this work, we discovered that
      contrary to previous reports, KASH domain-containing forms of Msp-300 are not
      required for viability, nor for oogenesis. However, we did find that Msp-300 has
      a function in egg laying, normally redundant with a function of Klar.

PMID- 18820483
TI  - Transducing the Hedgehog signal across the plasma membrane.
AB  - Cell signaling mediated by the Hedgehog (Hh) family of secreted proteins is
      essential for metazoan development and its malfunction causes congenital
      disorders and cancer. The seven-transmembrane protein Smoothened (Smo) transduces
      the Hh signal across the plasma membrane in both vertebrates and invertebrates
      but the underlying mechanisms remain ill defined. In Drosophila, Hh induces
      phosphorylation of Smo at multiple sites by PKA and CK1, leading to its cell
      surface accumulation and activation. Recently, we have obtained evidence that Hh
      induced phosphorylation promotes Smo activity by inducing a conformational switch
      and dimerization of its carboxy-terminal cytoplasmic tail (C-tail). Furthermore,
      we provided evidence that a similar mechanism regulates mammalian Smo. We discuss
      how Smo conformational change regulates the intracellular signaling complex and
      how Smo transduces the graded Hh signaling activities through different
      conformational states.

PMID- 18820484
TI  - Professionalism in clerkships: an analysis of MSPE commentary.
AB  - BACKGROUND: Professionalism in medical school predicts future behaviors. The
      authors assessed prevalence of references to professionalism behaviors in the
      clerkship commentary portion of Medical School Performance Evaluations (MSPEs).
      METHOD: Content analyses of 293 MSPEs submitted for 2005 graduates. RESULTS:
      Overall, 70% of MSPEs specifically mentioned professionalism; 96% included
      information about at least 1 of 16 professional behaviors. Internal Medicine
      referenced significantly more behaviors than other clerkships. Commentary about
      behaviors such as interactions (94%) and motivation (91%) was common; behaviors
      such as truthfulness (8%) and confidentiality (6%) were rarely mentioned. Fewer
      than 1% of comments could be considered negative. CONCLUSIONS: Most
      professionalism comments in MSPEs are generic and somewhat bland, tending to be
      about students' collegial interactions and hard work. More detail and breadth may
      be facilitated by wider use of behavior-centered evaluation in clerkships.

PMID- 18820485
TI  - The educational realities of increasing medical school class size.

PMID- 18820486
TI  - Assessing students for medical school admissions: is it time for a new approach?

PMID- 18820487
TI  - Who am I and why am I here? Professionalism research through the eyes of a
      medical student.

PMID- 18820488
TI  - Seeing the sights of RIME: resident as academic tourist.

PMID- 18820491
TI  - Setting standards for performance tests: a pilot study of a three-level Angoff
      method.
AB  - BACKGROUND: The Yes/No Angoff method is a standard-setting variant in which
      judges estimate whether a borderline student would or would not accomplish each
      item. However, when there is a 50% chance of success, systematically severe or
      lenient ratings may skew the cut score. This study piloted a three-level Angoff
      in which items were assigned to "Yes," "No," or "Maybe" categories. METHOD: Five
      judges provided three-level Angoff ratings for seven checklists used in a
      clinical skills exam for fourth-year students. Systematic severity and leniency
      were simulated by converting all "Maybe" ratings to "Yes" or "No" ratings,
      respectively. RESULTS: Forty-one percent of 121 items had at least one "Maybe"
      rating. Ten percent of all ratings were in the "Maybe" category. One judge
      accounted for 83% of all "Maybe" ratings; three did not use it at all. Case
      failure rates varied considerably depending on the simulated severity of ratings.
      Overall failure rates were not substantially impacted. CONCLUSIONS: The three
      level Angoff retains the cognitive simplicity of the Yes/No Angoff while
      addressing the challenge of items midrange for the borderline candidate.

PMID- 18820492
TI  - The impact of judge selection on standard setting for a patient survey of
      physician communication skills.
AB  - BACKGROUND: Patient surveys such as the Communication Assessment Tool (CAT) are
      recommended to assess physicians. Optimal methods to select judges and set a
      minimum passing standard (MPS) for a patient survey are unknown. METHOD: Fifty
      eight judges in five groups provided item-based (Angoff) and group-based
      (Hofstee) judgments for the CAT on two occasions. Judges were communication
      experts, program directors, trainees, and patients (two groups). Ratings were
      used to calculate MPSs for the CAT. Interrater reliability and test-retest
      reliability (stability) were estimated. MPSs were applied to data from a CAT
      pilot study. RESULTS: Judges produced different MPSs depending on their
      background. Patients and communication experts were most stringent in their MPS
      decisions; program directors and trainees were most lenient. Failure rates from
      the pilot study ranged from 0% to 47%. CONCLUSIONS: Judge expertise and
      background dramatically influenced MPSs for a patient survey of physician
      communication skills. Judge selection is a key decision when setting an MPS for a
      clinical skills evaluation.

PMID- 18820493
TI  - Measurement characteristics of content-parallel single-best-answer and extended
      matching questions in relation to number and source of options.
AB  - BACKGROUND: Previous research showed that extended-matching questions (EMQs) with
      eight options per set resulted in better score precision than EMQs with larger
      numbers of options or independent single-best-answer items (A-type) with five
      options. This study extends previous work using smaller numbers of options.
      METHOD: Ninety-six questions were presented in two formats on United States
      Medical Licensing Examination Step 2: as two-item EMQ sets and as independent A
      types. Four versions of EMQs were used: five- and eight-option versions with
      options selected using statistics, and five- and eight-option versions with
      options selected by physicians. Seven A-type versions were used: three-, four-,
      five-, and eight-option versions with options selected using statistics, and
      three-, four-, and five-option versions with options selected by physicians.
      RESULTS: Items with more options were harder, required more time to complete, and
      had similar item discrimination. Option sets selected by physicians were easier,
      slightly more discriminating, and required less testing time. CONCLUSIONS: A
      types with four or five options and EMQs with eight options make more efficient
      use of testing time. Provision of response statistics to content experts does not
      seem necessary to guide option selection.

PMID- 18820494
TI  - Tobacco world: evaluation of a tobacco cessation training program for third-year
      medical students.
AB  - BACKGROUND: Training in tobacco cessation counseling is deficient in medical
      schools. Tobacco World, a tobacco cessation training program, was implemented in
      a family medicine clerkship and subsequently evaluated. METHOD: In the pilot
      year, students were assigned to either standard clerkship training (comparison
      group) or a group that also received Tobacco World training (intervention group).
      All students received intervention training in the second year of the study. A 35
      item questionnaire was administered before and after the four-week clerkship to
      assess knowledge, attitude, and confidence regarding tobacco cessation
      counseling. RESULTS: Intervention training was highly rated. Students in the
      intervention group from both years demonstrated significant improvements in some
      key measurements of knowledge, attitude, confidence, and increased frequency of
      tobacco cessation counseling. CONCLUSIONS: This smoking cessation training
      program addresses an underrepresented area of medical school education and has
      the potential to translate into improved smoking cessation counseling by future
      physicians.

PMID- 18820495
TI  - Elapsed time between teaching and evaluation: does it matter?
AB  - BACKGROUND: Web-based course evaluation systems offer the potential advantage of
      timely evaluations. The authors examined whether elapsed time between teaching
      and student evaluation of teaching impacts preclinical courses' quality ratings.
      METHOD: The overall relationship of elapsed time with evaluation rating was
      explored with regression and ANOVA. Time between teaching event and evaluation
      was categorized by weeks. Within-teaching-events means and variances in
      evaluations related to elapsed weeks were compared using repeated-measures ANOVA.
      RESULTS: With more elapsed weeks, quality mean ratings increased (P < .001) and
      variability decreased (P < .001); effect sizes were small (average effect size =
      0.06). Trends were similar in regression analysis and for data aggregated by
      event. CONCLUSIONS: Summaries of event quality are negligibly impacted by
      evaluation timing. Future studies should examine the impact of other Web-based
      evaluation features on evaluation.

PMID- 18820496
TI  - Medical education in the Caribbean: variability in medical school programs and
      performance of students.
AB  - BACKGROUND: The purpose of this study was to examine the structure of medical
      training programs in the Caribbean and the performance of the students. METHOD:
      There are 56 medical schools in 16 countries currently recognized and open in the
      Caribbean. Almost 30,000 students from this region applied for exams leading to
      Educational Commission for Foreign Medical Graduates (ECFMG) certification
      between 1993 and 2007. The authors summarized school characteristics and pass
      rates on United States Medical Licensing Examinations, by country. RESULTS: The
      structure of medical education varies across the region, including existence of
      accrediting bodies and review processes. First-attempt pass rates by country
      ranged from 19.4% to 84.4% for Step 1, from 26.3% to 79.7% for the Step 2
      Clinical Knowledge Examination, and from 60.6% to 97.2% for the Step 2 Clinical
      Skills Examination. CONCLUSIONS: There is significant variability in
      undergraduate medical education and the performance of students of medical
      schools in Caribbean nations.

PMID- 18820497
TI  - The relationship between performance on a medical school's clinical skills
      assessment and USMLE Step 2 CS.
AB  - BACKGROUND: Little is known about the relationship between performance on
      clinical assessments during medical school and performance on similar licensing
      tests. METHOD: Correlation coefficients were computed and corrected for
      measurement error using data for 217 students who completed a school's clinical
      assessment and took the Step 2 Clinical Skills (CS) examination. RESULTS:
      Observed (and corrected) correlations between the two tests were 0.18 (0.32) for
      Data Gathering, 0.35 (0.75) for Documentation, and 0.32 (0.56) for
      Communication/Interpersonal Skills. The highest correlation within each test was
      between Documentation and Data Gathering. The lowest was between Documentation
      and Communication/ Interpersonal Skills. CONCLUSIONS: The pattern of correlations
      supports each test's construct validity. The low correlations suggest that the
      tests are not redundant, and do not support using the scores on the school's
      assessment to predict performance on Step 2 CS. Future studies of these
      relationships need to address the time between the two assessments and the effect
      of intervening remedial programs.

PMID- 18820498
TI  - The generalizability of documentation scores from the USMLE Step 2 Clinical
      Skills examination.
AB  - BACKGROUND: This research examined various sources of measurement error in the
      documentation score component of the United States Medical Licensing Examination
      (USMLE) Step 2 Clinical Skills examination. METHOD: A generalizability theory
      framework was employed to examine the documentation ratings for 847 examinees who
      completed the USMLE Step 2 Clinical Skills examination during an eight-day period
      in 2006. Each patient note was scored by two different raters allowing for a
      persons-crossed-with-raters-nested-in-cases design. RESULTS: The results suggest
      that inconsistent performance on the part of raters makes a substantially greater
      contribution to measurement error than case specificity. Double scoring the notes
      significantly increases precision. CONCLUSIONS: The results provide guidance for
      improving operational scoring of the patient notes. Double scoring of the notes
      may produce an increase in the precision of measurement equivalent to that
      achieved by lengthening the test by more than 50%. The study also cautions
      researchers that when examining sources of measurement error, inappropriate data
      collection designs may result in inaccurate inferences.

PMID- 18820499
TI  - Contrast effects in the USMLE Step 2 Clinical Skills examination.
AB  - BACKGROUND: As with any examination using human raters, it is possible that human
      subjectivity may introduce measurement error. An examinee's performance might be
      scored differently on the basis of the quality of the preceding performance(s)
      (contrast effects). This research investigated the presence of contrast effects,
      within and across test sessions, for the communication and interpersonal skills
      component of the United States Medical Licensing Examination Step 2 Clinical
      Skills (CS) examination. METHOD: Data from Step 2 CS examinees were analyzed
      using hierarchical and general linear modeling procedures. RESULTS: Contrast
      effect was significant for the communication and interpersonal skills score, both
      within and across test sessions. The effect was found to have a nontrivial impact
      on the overall score. CONCLUSIONS: The presence of contrast effects suggests that
      scores for an examinee are influenced by the performance of other examinees. More
      research is needed to fully understand these effects.

PMID- 18820500
TI  - Comprehensive changes in the learning environment: subsequent step 1 scores of
      academically at-risk students.
AB  - BACKGROUND: During the past 10 years at our institution, a number of changes have
      been instituted in the learning environment, including instructional techniques,
      assessment methods, academic support, and explicit board preparation. METHOD: The
      authors studied the Step 1 performance of students with MCAT scores of 20 to 25
      in our former and current curricula. Effect sizes were calculated for score
      improvement using adjusted means from ANCOVA with covariates of MCAT and age.
      RESULTS: The overall effect size was 0.48, with larger effects seen for
      underrepresented minority students overall (d = 0.64) and African American
      students especially (d = 0.77), representing medium to large effects. Overall
      failure rates decreased by two thirds. CONCLUSIONS: Comprehensive changes in the
      learning environment were followed by substantial improvement in Step 1
      performance among academically at-risk students.

PMID- 18820501
TI  - Development of an instrument to measure the climate of professionalism in a
      clinical teaching environment.
AB  - BACKGROUND: This report describes an instrument that measures professionalism in
      clinical environments, reports its psychometric properties, and discusses its
      potential uses. METHOD: The survey asked students (n = 371) to report the
      frequency of peers', residents', and faculty's professionalism behaviors and
      faculty's professionalism teaching, and it asked faculty (n = 28) to self-assess
      their teaching of professionalism. The authors investigated the instrument's
      reliability, convergent validity, and ability to detect differences between
      groups. RESULTS: Coefficient alphas were .75 or higher. Correlations showed
      positive relationships between students' perceptions of professionalism behaviors
      and faculty's professionalism teaching. t-tests indicated that preclinical
      students rated faculty's professionalism behaviors higher than did clinical
      students, and students rated faculty's professionalism teaching higher than the
      faculty rated themselves. CONCLUSIONS: The psychometrics of the instrument's
      scores are sound. The instrument has potential to meet the Liaison Committee on
      Medical Education's mandate to measure professional standards within learning
      environments and to track effects of interventions promoting the professionalism
      of learners and faculty.

PMID- 18820502
TI  - International exchange programs and U.S. medical schools.
AB  - BACKGROUND: International health experiences have been shown to increase
      students' and residents' interest in public health, their likelihood of choosing
      a career in primary care, and their commitment to serving the underserved. The
      purpose of the current study is to describe the international experiences
      available to students and residents at U.S. allopathic medical schools. METHOD:
      An online survey was conducted to collect information about the types of
      international opportunities in medical education provided to faculty, students,
      and residents at U.S. allopathic medical schools. RESULTS: Reponses from 103
      representatives of 96 U.S. allopathic medical schools were included in the
      analysis. A variety of opportunities for students and residents was reported,
      with 59% of the respondents reporting elective rotations for residents, 11%
      reporting a global health track for students, and 45% reporting opportunities to
      perform preclinical research abroad. CONCLUSIONS: Despite associated costs and
      risks, U.S. medical schools are developing and refining international health
      experiences for medical students and residents.

PMID- 18820503
TI  - A multilevel analysis of examinee gender and USMLE step 1 performance.
AB  - BACKGROUND: To examine the effects of (1) examinee gender on United States
      Medical Licensing Examination (USMLE) Step 1 performance, (2) examinee gender on
      the relationships between prematriculation measures and Step 1 performance, and
      (3) medical school characteristics on the relationships between examinee
      characteristics and Step 1 performance. METHOD: A series of hierarchical linear
      models (examinees-nested-in-schools) was conducted predicting Step 1 scores. The
      sample included 66,412 examinees from 133 U.S. Liaison Committee on Medical
      Education-accredited medical schools/campuses. RESULTS: Controlling for
      prematriculation measures, men outperformed women slightly on Step 1.
      Undergraduate science grade point averages were more associated with Step 1
      performance for women than men. Schools with higher mean Medical College
      Admission Test (MCAT) science scores had higher mean Step 1 scores, and MCAT
      science scores were slightly more associated with Step 1 performance for students
      from schools with higher percentages of female students. CONCLUSIONS: Patterns of
      gender-related performance differences on Step 1 generally mirrored those
      reported in earlier research. School-level variables provided some additional
      insight into these relationships, but additional research is needed to fully
      understand why men and women perform differently on the USMLE.

PMID- 18820504
TI  - Procedural and interpretive skills of medical students: experiences and attitudes
      of fourth-year students.
AB  - BACKGROUND: Recent data do not exist regarding fourth-year medical students'
      performance of and attitudes toward procedural and interpretive skills, and how
      these differ from third-year students'. METHOD: Cross-sectional survey conducted
      in February 2006 of 122 fourth-year students from seven U.S. medical schools,
      compared with their responses in summer 2005. Students estimated their cumulative
      performance of 22 skills and reported self-confidence and perceived importance
      using a five-point Likert-type scale. RESULTS: The response rate was 79%
      (96/122). A majority reported never having performed cardioversion,
      thoracentesis, cardiopulmonary resuscitation, blood culture, purified protein
      derivative placement, or paracentesis. One fifth of students had never performed
      peripheral intravenous catheter insertion, phlebotomy, or arterial blood
      sampling. Students reported increased cumulative performance of 17 skills,
      increased self-confidence in five skills, and decreased perceived importance in
      three skills (two-sided P < .05). CONCLUSIONS: A majority of fourth-year medical
      students still have never performed important procedures, and a substantial
      minority have not performed basic procedures.

PMID- 18820505
TI  - Impact of a structured skills laboratory curriculum on surgery residents'
      intraoperative decision-making and technical skills.
AB  - BACKGROUND: This project sought to study the effectiveness of a curriculum to
      enhance the intraoperative clinical judgment and procedural skill of surgical
      residents. METHOD: A multiinstitutional, prospective, randomized study was
      performed. A cognitive task analysis of laparoscopic cholecystectomy (LC) was
      conducted on which instructional activities and measurement instruments were
      designed. Residents were randomly assigned to a control or intervention group.
      Subjects took written pre- and posttests examining procedure-related judgment and
      knowledge. The intervention group participated in a three-session curriculum
      emphasizing LC critical decisions and error prevention. All subjects were
      evaluated performing the procedure on a cadaveric model. Scores from written and
      practical exams were compared using independent-sample and paired Student t
      tests. RESULTS: Written examination scores increased for both groups. The
      intervention group scored significantly higher (P < .05) on the written posttest
      than the control group. There were no differences between groups on the practical
      examination. Reliability coefficients for the written examination ranged from .65
      to .75. Reliability coefficients for the oral exam, technical skill, and error
      items on the porcine practical exam were .83, .90, and .53. CONCLUSIONS: The
      curriculum resulted in enhanced performance on a written exam designed to assess
      intraoperative judgment, but no differences in technical skills, showing
      important implications for future skills lab curriculum formats.

PMID- 18820506
TI  - A comparison of alternative item weighting strategies on the data gathering
      component of a clinical skills performance assessment.
AB  - BACKGROUND: Checklist scores used to produce the data gathering score on the Step
      2 CS examination are currently weighted using an algorithm based on expert
      judgment about the importance of the item. The present research was designed to
      compare this approach with alternative weighting strategies. METHOD: Scores from
      21,140 examinees who took the United States Medical Licensing Examination Step 2
      between May 2006 and February 2007 were subjected to five weighting models: (1) a
      regression weights model, (2) a factor loading weights model, (3) a standardized
      response model, (4) an equal weights model, and (5) the operational expert
      judgment weights model. RESULTS: Alternative weighting procedures may have a
      significant impact on the reliability and validity of checklist scores.
      CONCLUSIONS: The results suggest that the current weighting procedure is useful,
      and the regression-based model holds promise for practical application. The
      regression-based model produces scores that are more reliable than those produced
      by the current procedure and more strongly related to the external criteria.

PMID- 18820507
TI  - Interprofessional communication and medical error: a reframing of research
      questions and approaches.
AB  - Progress toward understanding the links between interprofessional communication
      and issues of medical error has been slow. Recent research proposes that this
      delay may result from overlooking the complexities involved in interprofessional
      care. Medical education initiatives in this domain tend to simplify the
      complexities of team membership fluidity, rotation, and use of communication
      tools. A new theoretically informed research approach is required to take into
      account these complexities. To generate such an approach, we review two theories
      from the social sciences: Activity Theory and Knotworking. Using these
      perspectives, we propose that research into interprofessional communication and
      medical error can develop better understandings of (1) how and why medical errors
      are generated and (2) how and why gaps in team defenses occur. Such complexities
      will have to be investigated if students and practicing clinicians are to be
      adequately prepared to work safely in interprofessional teams.

PMID- 18820508
TI  - Retention of basic science information by senior medical students.
AB  - BACKGROUND: Studies of retention of basic science information have commonly
      demonstrated a knowledge decline as students progress through medical education.
      This study examined item characteristics influencing patterns of retention.
      METHOD: A large content and statistically representative sample of basic science
      items from 2004-2005 forms of United States Medical Licensing Examination (USMLE)
      Step 1 was included in unscored sections of 2004-2005 USMLE Step 2 Clinical
      Knowledge (CK) test forms, and the performance of 15,000+ first-time examinees
      from U.S. and Canadian schools was analyzed to identify item characteristics
      affecting retention. RESULTS: Across the 502 study items, the mean item
      difficulty on Step 1 was 76.1%; on Step 2 CK, this value declined to 69.7%.
      Performance declines were largest in Biochemistry (17.5%) and Microbiology
      (12.6%). Improvement was only observed for Behavioral Sciences items (8.7%).
      CONCLUSIONS: Shifts in examinee performance in this study were similar to those
      observed in previous research, although the magnitude of the overall decline was
      somewhat larger.

PMID- 18820509
TI  - Exploring the learning curve in medical education: using self-assessment as a
      measure of learning.
AB  - BACKGROUND: Learning is a complex process that follows predictable patterns. The
      authors explored whether students' self-assessment of competencies could be used
      as a measure of learning within medical school. METHOD: Medical students (all
      grade levels) rated their achievement of competencies at the beginning and end of
      an academic year. Repeated-measures ANOVA and [eta]2 were used to determine
      differences. RESULTS: Five hundred thirty-three students participated (response
      rate = 79.3%). Self-assessment ratings between four grade levels were significant
      (P < .001, [eta]2 = 0.33), with the steepest difference between MS2 and MS3;
      professionalism ratings remained relatively stable. The largest percent increase
      within an academic year occurred between MS1 and MS2, with little increase within
      MS3 and MS4. CONCLUSIONS: Medical students' self-assessment ratings of
      competencies indicated differences between grade levels and during an academic
      year, following a sigmoidal curve. These results have implications for medical
      education and indicate the need to develop longitudinal measures to track changes
      in learning.

PMID- 18820510
TI  - Point-of-care assessment of medical trainee competence for independent clinical
      work.
AB  - BACKGROUND: Clinical supervisors make frequent assessments of medical trainees'
      competence so they can provide appropriate opportunities for trainees to
      experience clinical independence. This study explored context-specific
      assessments of trainees' competence for independent clinical work. METHOD: In
      Phase One, 88 teaching team members from internal and emergency medicine were
      observed during clinical activities (216 hours), and 65 participants completed
      brief interviews. In Phase Two, 36 in-depth interviews were conducted using video
      vignettes. Data collection and analysis employed grounded theory methodology.
      RESULTS: Supervisors' assessments of trainee trustworthiness for independent
      clinical work involved consideration of four dimensions: knowledge/skill,
      discernment of limitations, truthfulness, and conscientiousness. Supervisors'
      reliance on language cues as a source of trustworthiness data was revealed.
      CONCLUSIONS: This study provides an initial exploration of context-specific
      competence assessments, which affect both patient safety and education, and
      provides a novel framework for study of the links between language use and
      competence.

PMID- 18820511
TI  - Collecting validity evidence for an assessment of professionalism: findings from
      think-aloud interviews.
AB  - BACKGROUND: This study investigated whether participants' subjective reports of
      how they assigned ratings on a multisource feedback instrument provide evidence
      to support interpreting the resulting scores as objective, accurate measures of
      professional behavior. METHOD: Twenty-six participants completed think-aloud
      interviews while rating students, residents, or faculty members they had worked
      with previously. The items rated included 15 behavioral items and one global
      item. RESULTS: Participants referred to generalized behaviors and global
      impressions six times as often as specific behaviors, rated observees in the
      absence of information necessary to do so, relied on indirect evidence about
      performance, and varied in how they interpreted items. CONCLUSIONS: Behavioral
      change becomes difficult to address if it is unclear what behaviors raters
      considered when providing feedback. These findings highlight the importance of
      explicitly stating and empirically investigating the assumptions that underlie
      the use of an observational assessment tool.

PMID- 18820512
TI  - Cross-sectional assessment of medical and nursing students' attitudes toward
      chronic illness at matriculation and graduation.
AB  - BACKGROUND: It is important to assess students' attitudes toward chronic illness
      to enhance curriculum and support interprofessional learning. METHOD: A 40-item
      questionnaire was administered to 704 medical and nursing students. Qualitative
      and quantitative analyses examined their attitudes and understanding of chronic
      illness as well as differences between medical and nursing students. RESULTS:
      Content analysis and factor analysis indicated that entering students were more
      positive about chronic illness than graduates. Most underestimated its economic
      impact. Positive attitudes toward chronic illness were associated with taking a
      personal interest in patients. The attitudes of nursing students were generally
      similar to those of medical students, but there were differences related to
      patient adherence, the role of nurses in patient education, managing
      comorbidities, and confidentiality of electronic medical records. CONCLUSIONS:
      Entering students were more positive about chronic illness than graduates.
      Although medical and nursing students' attitudes were very similar, differences
      have implications for interprofessional education.

PMID- 18820513
TI  - Rules of engagement: residents' perceptions of the in-training evaluation
      process.
AB  - BACKGROUND: In-training evaluation reports (ITERs) often fall short of their
      goals of promoting resident learning and development. Efforts to address this
      problem through faculty development and assessment-instrument modification have
      been disappointing. The authors explored residents' experiences and perceptions
      of the ITER process to gain insight into why the process succeeds or fails.
      METHOD: Using a grounded theory approach, semistructured interviews were
      conducted with 20 residents. Constant comparative analysis for emergent themes
      was conducted. RESULTS: All residents identified aspects of "engagement" in the
      ITER process as the dominant influence on the success of ITERs. Both external
      (evaluator-driven, such as evaluator credibility) and internal (resident-driven,
      such as self-assessment) influences on engagement were elaborated. When
      engagement was lacking, residents viewed the ITER process as inauthentic.
      CONCLUSIONS: Engagement is a critical factor to consider when seeking to improve
      ITER use. Our articulation of external and internal influences on engagement
      provides a starting point for targeted interventions.

PMID- 18820514
TI  - Does the consistent application of criteria for faculty promotion lead to fair
      decisions?

PMID- 18820515
TI  - Commentary: training internists for practice focused on meeting patient needs.
AB  - The author describes the evolution of practice within the broad specialty of
      internal medicine. This evolution is driven by scientific discovery, emergent
      patient needs, and market forces. Four ages describe the evolution: the age of
      the Oslerian diagnostic consultant, the age of the subspecialist, the age of the
      primary care internist, and the emerging age of focused general internal medicine
      practice. The author suggests that competence in practice-based learning and
      improvement linked with evaluation of practice performance throughout a career
      permits the professions to abandon the notion that valid learning for medical
      practice occurs only by completing a designated number of months of residency or
      fellowship training. By applying competency-based standards for specialty
      certification and maintaining its validity for current practice, boards can
      provide trainees and practitioners a tool for professional accountability for
      initial and continuous professional competence. The lifelong learning and
      evaluation process permits the timely recognition of proficiency acquired in
      practice. This process engages internists in ongoing guided reflection on
      measures of performance and provides evidence that they have incorporated new
      knowledge, technology, skills, and attitudes that align their practice with
      patient needs. As dialogue with internal medicine stakeholders and customers
      continues, the author describes how the training standards for certification
      might adapt to the evolving demands for the specialty practice and how the
      evaluation of continuous professional development through the maintenance of
      certification provides an instrument for identifying and recognizing proficiency
      in providing focused care within the broad discipline of internal medicine.

PMID- 18820516
TI  - Commentary: Osler in a brave new world.
AB  - The current issue of Academic Medicine includes a proposal to reform internal
      medicine residency education by returning to the Oslerian ideal of an internist
      as a consultant-generalist. To meet this goal, the proposed model focuses on a
      traditional inpatient learning experience with outpatient learning structured in
      blocks rather than continuity clinics. In this commentary, the author contends
      that today's learning environment is significantly different from the learning
      environment of the 1890s when the Oslerian ideal was conceived. Inpatient wards
      are often filled with patients who arrive to the hospital ward with a diagnosis
      already made. Residency education needs to take into account the technological
      and scientific advances of today's age to ensure that residents are learning the
      fundamental skills required of all physicians--delivering a precise differential
      diagnosis which leads to the ultimate evaluation and treatment plan. Meaningful
      experience with patients who cover the full spectrum of health and illness will
      bring the most robust learning for our residents. To attain these experiences,
      our residents must practice in a variety of environments, including in inpatient
      services, intensive care units, and outpatient clinics. Just as in designing a
      well-balanced financial portfolio, educational programs must be equally well
      balanced to achieve the learning and patient outcomes that residents expect and
      patients deserve.

PMID- 18820517
TI  - Sharpening the eye of the OSCE with critical action analysis.
AB  - PURPOSE: When interpreting performance scores on an objective structured clinical
      examination (OSCE), are all checklist items created equal? Although assigning
      priority through checklist item weighting is often used to emphasize the clinical
      importance of selected checklist items, the authors propose the use of critical
      action analysis as an additional method for analyzing and discriminating clinical
      performance in clinical skill assessment exercises. A critical action is defined
      as an OSCE checklist item whose performance is critical to ensure an optimal
      patient outcome and avoid medical error. In this study, the authors analyzed a
      set of clerkship OSCE performance outcome data and compared the results of
      critical action analysis versus traditional checklist item performance scores.
      METHOD: OSCE performance scores of 398 third-year clerkship students from 2003 to
      2006 at the University of Virginia School of Medicine were analyzed using
      descriptive statistics and a logistic regression model. Through a consensus
      process, 10 of 25 OSCE cases were identified as containing critical actions.
      RESULTS: Students who scored above the median correctly performed the critical
      actions more often than those scoring lower. However, for 9 of 10 cases, 6% to
      46% of higher-scoring students failed to perform the critical action correctly.
      CONCLUSIONS: Failure to address this skill assessment outcome is a missed
      opportunity to more fully understand and apply the results of such examinations
      to the clinical performance development of medical students. Including critical
      action analysis in OSCE data interpretation sharpens the eye of the OSCE and
      enhances its value in clinical skill assessment.

PMID- 18820518
TI  - Perspective: moving students beyond an organ-based approach when teaching medical
      interviewing and physical examination skills.
AB  - Medical interviewing and physical examination skills are core pillars of clinical
      medicine. Though nearly all U.S. medical students participate in preclinical
      courses designed to teach these skills, medical school faculty often comment that
      students' abilities remain limited on entering their clinical clerkships. The
      reason for this contention is not clear.The author briefly describes the current
      preclinical curricula at most medical schools that are designed to teach patient
      interviewing and examination. An organ-based curriculum is commonly employed,
      although the limitations of such an approach readily become apparent. For
      example, many hospitalized patients do not suffer from single-organ illnesses,
      but rather from infections or metabolic derangements, which cause numerous
      abnormalities to several body systems. Furthermore, clinical reasoning skills are
      rarely taught in such preclinical courses, though these abilities form the
      foundation for effective doctoring. These findings suggest an opportunity for
      content development surrounding patient interviewing and examination. The author
      proposes an educational approach that depicts how the confluence of both content
      knowledge skills and clinical reasoning skills can work synergistically to
      enhance preclinical teaching of the medical interview and physical examination.

PMID- 18820519
TI  - Internal medicine training in the 21st century.
AB  - Many are calling for changes for internal medicine training, arguing that changes
      in the practice environment mandate changes in how the internal medicine
      residency is structured. Residency could be shorter, more conducive to role
      differentiation among general internists, and more supportive of
      subspecialization. Training could provide more experience in ambulatory care,
      multidisciplinary team-based care, chronic disease management, and quality
      improvement. The authors contend that the claim that internal medicine training
      ought to mirror internal medicine practice is mistaken. Many changes now proposed
      would likely damage if not destroy the consultant-generalist ideal of traditional
      internal medicine training which remains critical to effective medical care in
      the 21st century. The authors propose a model for training similar in structure
      but different in spirit from contending models. This model, like others, would
      involve a core experience in the first two years with tracking in the final year;
      unlike others, it would provide a conceptually coherent experience based on
      internal medicine's traditional ideal. Outpatient experience would be subsidiary
      to a predominantly inpatient experience, and it would be structured in blocks
      rather than continuity clinics. Twenty-first-century internists will continue to
      face what has always been the internist's task: the resolution of complex and ill
      defined patient problems into proper diagnoses and therapeutic options.
      Contemporary internal medicine training must fit trainees for that task and must,
      thus, continue to offer the training experience necessary for the realization of
      the Oslerian ideal: a substantial apprenticeship taking care of inpatients with a
      wide range of medical illnesses.

PMID- 18820520
TI  - Experiential learning of systems-based practice: a hands-on experience for first
      year medical residents.
AB  - Systems-based practice, a domain of expertise mandated for all residencies by the
      Accreditation Council for Graduate Medical Education, requires an
      interdisciplinary approach that involves communicating with the other members of
      the health care team as well as utilizing the many components of health care
      delivery. The Mercy Catholic Medical Center internal medicine residency
      leadership developed a two-week supervised experience in systems-based practice
      for first-year medical residents to give them firsthand experience with
      nonphysician providers' delivery of health care. The disciplines in the
      experience were home care services, hospice care, pharmacy services, laboratory
      services, utilization services, and nutrition services. Nonphysician health care
      providers willingly made themselves available for this educational activity
      because they felt that such face-to-face interaction fosters an improved
      understanding of their discipline and its services in the participating
      physicians. Surveys of resident knowledge pre- and postworkshop suggested that
      the residents' rudimentary understanding of these disciplines developed into both
      a deeper theoretical understanding and a greater knowledge of specific policies
      regarding these health care services. This type of experience is likely a
      necessary first step toward developing physicians who can provide
      interdisciplinary medical care that integrates the many other health care
      disciplines into a comprehensive plan to maximize health outcomes. As physicians
      become leaders of multidisciplinary teams in the 21st century, firsthand
      knowledge of the other health services enhances their capacity to maximize the
      services of these other disciplines for the benefit of patient care.

PMID- 18820521
TI  - The design and implementation of a multidisciplinary global health residency
      track at the Mount Sinai School of Medicine.
AB  - The Mount Sinai Global Health Center established a new multidisciplinary Global
      Health Residency Track (GHRT) in 2006. The goal of the GHRT is to provide
      participants with a foundation in global health issues and population-based
      health care, a chance to develop basic research and public health skills in the
      field, and guidance for career development. The authors describe how the GHRT was
      created, present its structure, and discuss their experience implementing this
      new program. Other selected global health residency training programs are also
      reviewed. The Mount Sinai GHRT is a two-year program that comprises a didactic
      curriculum, with participants required to take selected classes in the Master of
      Public Health Program of the Mount Sinai School of Medicine of New York
      University, and "field experience," which consists of a public health project
      that is implemented during a two-month elective period during the second year.
      Core competencies include (1) epidemiology and research skills, (2) health
      disparities, human rights, and cultural competency, (3) needs assessment and
      project development, (4) tropical medicine and infectious disease, and (5)
      reproductive, maternal, and child health. Nine residents were selected from four
      Mount Sinai residency programs to participate in the GHRT in its first year, and,
      during the winter of 2007, senior residents conducted public health projects in
      the Dominican Republic, India, Kenya, and East Harlem. All components of the
      track performed well in evaluations. An outcomes survey is ongoing to track
      career choices among graduates and to identify barriers to continuing involvement
      in global health.

PMID- 18820522
TI  - A conceptual framework for interprofessional and co-managed care.
AB  - Interprofessional care has been promoted by some policy makers and health
      professionals as a response to rising health care costs and threats to patient
      safety. Proponents suggest that interprofessional models of care can reduce
      fragmentation and lower costs through improved coordination between different
      health professionals. These models encourage the collaboration of supplementary
      skills between different health care professionals. Effective collaborative
      models of interprofessional care may be influenced by several variables germane
      to the interaction and structure of the team of health professionals-
      temporality, urgency, and degree of structured authority--and the author examines
      the importance of each variable in delivering interprofessional care. Co-managed
      models of care have also been proposed. Recent state health reform efforts have
      catalyzed the adoption of co-managed care models by expanding the autonomy of
      alternative providers through the broadening of scope of practice. These scope-of
      practice changes are intended to permit greater diagnostic and therapeutic
      authority of nonphysician providers. This effort seems aimed at enhancing the
      competition between provider groups in the market and expanding consumer choices.
      Herein, the author presents a conceptual framework to describe different models
      of interprofessional and co-managed care. The author also considers
      interprofessional and co-managed care models in the context of the health reform
      movement. Some of the challenges are considered, as policy makers consider the
      options for facilitating further development of interprofessional models of
      practice and the implications for curricular modifications at academic health
      centers.

PMID- 18820523
TI  - Making interprofessional education work: the strategic roles of the academy.
AB  - Faculties (i.e., schools) of medicine along with their sister health discipline
      faculties can be important organizational vehicles to promote, cultivate, and
      direct interprofessional education (IPE). The authors present information they
      gathered in 2007 about five Canadian IPE programs to identify key factors
      facilitating transformational change within institutional settings toward
      successful IPE, including (1) how successful programs start, (2) the ways
      successful programs influence academia to bias toward change, and (3) the ways
      academia supports and perpetuates the success of programs. Initially, they
      examine evidence regarding key factors that facilitate IPE implementation, which
      include (1) common vision, values, and goal sharing, (2) opportunities for
      collaborative work in practice and learning, (3) professional development of
      faculty members, (4) individuals who are champions of IPE in practice and in
      organizational leadership, and (5) attention to sustainability. Subsequently,
      they review literature-based insights regarding barriers and challenges in IPE
      that must be addressed for success, including barriers and challenges (1) between
      professional practices, (2) between academia and the professions, and (3) between
      individuals and faculty members; they also discuss the social context of the
      participants and institutions. The authors conclude by recommending what is
      needed for institutions to entrench IPE into core education at three levels:
      micro (what individuals in the faculty can do); meso (what a faculty can
      promote); and macro (how academic institutions can exert its influence in the
      health education and practice system).

PMID- 18820524
TI  - Speaking the right language: the scientific method as a framework for a
      continuous quality improvement program within academic medical research
      compliance units.
AB  - The authors developed a novel continuous quality improvement (CQI) process for
      academic biomedical research compliance administration. A challenge in developing
      a quality improvement program in a nonbusiness environment is that the
      terminology and processes are often foreign. Rather than training staff in an
      existing quality improvement process, the authors opted to develop a novel
      process based on the scientific method--a paradigm familiar to all team members.
      The CQI process included our research compliance units. Unit leaders identified
      problems in compliance administration where a resolution would have a positive
      impact and which could be resolved or improved with current resources. They then
      generated testable hypotheses about a change to standard practice expected to
      improve the problem, and they developed methods and metrics to assess the impact
      of the change. The CQI process was managed in a "peer review" environment. The
      program included processes to reduce the incidence of infections in animal
      colonies, decrease research protocol-approval times, improve compliance and
      protection of animal and human research subjects, and improve research protocol
      quality. This novel CQI approach is well suited to the needs and the unique
      processes of research compliance administration. Using the scientific method as
      the improvement paradigm fostered acceptance of the project by unit leaders and
      facilitated the development of specific improvement projects. These quality
      initiatives will allow us to improve support for investigators while ensuring
      that compliance standards continue to be met. We believe that our CQI process can
      readily be used in other academically based offices of research.

PMID- 18820525
TI  - The fine arts examine the medical arts: anatomy 101.

PMID- 18820526
TI  - Medicine and the arts. Fitful Tango by Denice Cora-Bramble, MD, MBA. Commentary.

PMID- 18820528
TI  - A comprehensive medical education program response to rural primary care needs.
AB  - This article presents the characteristics and results of the Rural Medical
      Education (RMED) Program which addresses medical workforce needs focused on
      reducing rural health disparities. The program is comprehensive in implementing a
      system of recruitment of candidates from rural backgrounds, offering a rural
      focused curriculum, and instituting evaluative components to track outcomes.
      Distinctive program features include a Recruitment and Retention Committee of
      rural community members; special rural-focused topics and events during the first
      three years of undergraduate medical education; and a required fourth-year, 16
      week rural preceptorship through which students work with primary care physicians
      and conduct community-oriented primary care projects. Since 1993, 216 students
      have matriculated. More than three quarters of candidates interviewed received
      offers into the program (overall acceptance rate of 75%). Comparisons between
      RMED and all other students on composite MCAT scores and United States Medical
      Licensing Examination (USMLE) Part 1 scores show a slightly lower MCAT average
      for RMED students, but USMLE scores are equal to those of non-RMED students. To
      date, 159 students have graduated, with 76% entering primary care residencies;
      103 are currently in practice, with 64.4% in primary care practice in small towns
      and/or rural communities. RMED Program outcomes compare favorably with those of
      other rural medical education programs. RMED can serve as a model at many levels,
      including recruitment, collaboration, curriculum, and retention. Future
      challenges for program development and disparity reduction include recruiting
      students from the growing number of rural minority populations, expanding the
      number of program slots, and integrating the program with other health
      professions to address the needs of rural populations.

PMID- 18820529
TI  - A successful failure.

PMID- 18820530
TI  - Faculty performance evaluation in accredited U.S. public health graduate schools
      and programs: a national study.
AB  - PURPOSE: To provide baseline data on evaluation of faculty performance in U.S.
      schools and programs of public health. METHOD: The authors administered an
      anonymous Internet-based questionnaire using PHP Surveyor. The invited sample
      consisted of individuals listed in the Council on Education for Public Health
      (CEPH) Directory of Accredited Schools and Programs of Public Health. The authors
      explored performance measures in teaching, research, and service, and assessed
      how faculty performance measures are used. RESULTS: A total of 64 individuals
      (60.4%) responded to the survey, with 26 (40.6%) reporting
      accreditation/reaccreditation by CEPH within the preceding 24 months. Although
      all schools and programs employ faculty performance evaluations, a significant
      difference exists between schools and programs in the use of results for merit
      pay increases and mentoring purposes. Thirty-one (48.4%) of the organizations
      published minimum performance expectations. Fifty-nine (92.2%) of the respondents
      counted number of publications, but only 22 (34.4%) formally evaluated their
      quality. Sixty-two (96.9%) evaluated teaching through student course evaluations,
      and only 29 (45.3%) engaged in peer assessment. Although aggregate results of
      teaching evaluation are available to faculty and administrators, this information
      is often unavailable to students and the public. Most schools and programs
      documented faculty service activities qualitatively but neither assessed it
      quantitatively nor evaluated its impact. CONCLUSIONS: This study provides insight
      into how schools and programs of public health evaluate faculty performance.
      Results suggest that although schools and programs do evaluate faculty
      performance on a basic level, many do not devote substantial attention to this
      process.

PMID- 18820531
TI  - Centralized oversight of physician-scientist faculty development at Vanderbilt:
      early outcomes.
AB  - PURPOSE: In 2000, faced with a national concern over the decreasing number of
      physician-scientists, Vanderbilt School of Medicine established the
      institutionally funded Vanderbilt Physician-Scientist Development (VPSD) program
      to provide centralized oversight and financial support for physician-scientist
      career development. In 2002, Vanderbilt developed the National Institutes of
      Health (NIH)-funded Vanderbilt Clinical Research Scholars (VCRS) program using a
      similar model of centralized oversight. The authors evaluate the impact of the
      VPSD and VCRS programs on early career outcomes of physician-scientists. METHOD:
      Physician-scientists who entered the VPSD or VCRS programs from 2000 through 2006
      were compared with Vanderbilt physician-scientists who received NIH career
      development funding during the same period without participating in the VPSD or
      VCRS programs. RESULTS: Seventy-five percent of VPSD and 60% of VCRS participants
      achieved individual career award funding at a younger age than the comparison
      cohort. This shift to career development award funding at a younger age among
      VPSD and VCRS scholars was accompanied by a 2.6-fold increase in the number of
      new K awards funded and a rate of growth in K-award dollars at Vanderbilt that
      outpaced the national rate of growth in K-award funding. CONCLUSIONS: Analysis of
      the early outcomes of the VPSD and VCRS programs suggests that centralized
      oversight can catalyze growth in the number of funded physician-scientists at an
      institution. Investment in this model of career development for physician
      scientists may have had an additive effect on the recruitment and retention of
      talented trainees and junior faculty.

PMID- 18820532
TI  - The impact of facilitation of small-group discussions of psychosocial topics in
      medicine on faculty growth and development.
AB  - PURPOSE: To use qualitative analysis of interview transcripts with clinician
      educators who facilitate small-group discussions on psychosocial themes-
      including doctoring--to answer the question, "What impact does facilitating small
      group discussions of the patient's experience with chronic illness, the doctor
      patient relationship, and doctoring have on faculty instructors' attitudes
      regarding their roles as clinicians and teachers?" METHOD: In 2006, in-depth,
      face-to-face interviews using an open-ended question format were conducted with
      individual faculty small-group instructors teaching in the Family Centered
      Experience and Longitudinal Case Studies courses at the University of Michigan
      Medical School. Interview transcripts were analyzed using grounded theory
      methodology to identify emerging themes. Accuracy of interpretations and
      saturation of themes was confirmed by repeated contextual reading of the
      transcripts. RESULTS: Several major thematic codes emerged from the data.
      Facilitation of small-group discussions of psychosocial topics and doctoring
      fostered reflective approaches to patient care and teaching; enhanced
      interpersonal relationships between facilitators and their students, colleagues,
      and patients; and acted as a source of fulfillment and renewal among faculty
      facilitators. CONCLUSIONS: Small-group teaching of the art of doctoring may
      stimulate personal and professional growth among faculty facilitators and renewed
      interest in teaching and patient care.

PMID- 18820533
TI  - Do medical students know enough about smoking to help their future patients?
      Assessment of New York City fourth-year medical students' knowledge of tobacco
      cessation and treatment for nicotine addiction.
AB  - PURPOSE: Practicing physicians underutilize U.S. Department of Health and Human
      Services evidence-based approaches to nicotine addiction and treatment. Few
      studies have assessed medical student knowledge in this area. This study examined
      New York City fourth-year medical students' knowledge of tobacco cessation and
      treatment of nicotine addiction. METHOD: The authors conducted a Web-based
      survey, comprising 27 closed- and open-ended questions, of six of seven New York
      City medical schools in the spring of 2004. They drew questions from
      international, national, and local surveys on tobacco and health, U.S. Department
      of Health and Human Services tobacco treatment guidelines, and prior studies.
      Primary outcome measures were knowledge of the epidemiology of smoking, benefits
      of cessation and treatment of nicotine addiction, clinical cessation practices,
      and students' use of tobacco and intentions to stop smoking. RESULTS: Of 943
      fourth-year medical students, 469 (50%) completed an online survey. Students had
      good knowledge of the epidemiology of smoking, including its prevalence and
      health effects, with most responding correctly to relevant questions (mean
      correct response 79%; SD = 9.4). Students demonstrated a fair understanding of
      the benefits of cessation (mean correct response, 67%; SD = 19.2) and treatment
      of nicotine addiction (mean correct response, 61%; SD = 13.2). Three hundred
      students (64%) rated their own preparation to assist patients to quit as less
      than adequate. CONCLUSIONS: Fourth-year medical students at the participating
      schools in New York City understood the harms of smoking but needed more
      information on the benefits of stopping smoking and treatment of nicotine
      addiction.

PMID- 18820534
TI  - Beyond appearances.

PMID- 18820535
TI  - Low-dose, once-daily atazanavir/ritonavir (200/100): an effective treatment for
      HIV-infected patients in Thailand.

PMID- 18820536
TI  - Recurrence of skin and soft tissue infection caused by methicillin-resistant
      Staphylococcus aureus in a HIV primary care clinic.

PMID- 18820537
TI  - Uncommon hepatitis B virus and/or hepatitis C virus occult infection in HIV
      positive patients with abnormal level of hepatic enzyme.

PMID- 18820538
TI  - Vulvodynia in preadolescent girls.
AB  - OBJECTIVE: Although vulvodynia occurs in approximately 7% of adult American
      women, we hypothesize that vulvodynia also occurs in young girls and that they
      respond to treatments that are similar to those used in women with this disorder.
      MATERIALS AND METHODS: This is a retrospective case study of vulvodynia in
      preadolescent girls seen in our referral practice. Records of all office visits
      and any telephone or e-mailed follow-up were reviewed. RESULTS: Between October
      1996 and April 2006, 6 girls ages 4 to 11 years were evaluated and diagnosed with
      vulvodynia. Pain had been present for several months to 7 years, and most
      patients had been seen by several physicians before having this diagnosis made.
      Treatment was typically initiated with a tricyclic antidepressant, and 5 of the 6
      girls noted improvement in their symptoms, including 2 who had marked
      improvement, and another 3 with substantial improvement who were able to
      discontinue therapy without a recurrence. CONCLUSIONS: Vulvodynia does occur
      among young girls and, when treated as a neuropathic pain disorder, was found to
      dramatically improve or remit in the majority of those treated in this small case
      series. This underrecognized disorder should be considered in cases of ongoing
      vulvar discomfort, regardless of age.

PMID- 18820539
TI  - Association of DRB1 and DQB1 HLA class II polymorphisms in high-grade and
      neoplastic cervical lesions of women from Argentina.
AB  - OBJECTIVES: To investigate associations between HLA-DRB1 and HLA-DQB1
      polymorphisms with low- and high-grade cervical lesions in Argentine population
      and the role human papillomavirus status in these associations. MATERIALS AND
      METHODS: Cervical biopsies and peripheral blood samples were taken from 32
      patients with cervical intraepithelial neoplasia grade 1 (CIN 1) and 44 patients
      with cervical CIN 3 or invasive squamous cell carcinomas. Cervical cells and
      peripheral blood samples from 40 healthy women were included as control group.
      Human papillomavirus detection and typing were done by polymerase chain reaction
      (PCR) MY09, 11-restriction fragment length polymorphisms, or PCR 5+, 6+ dot-blot
      hybridization, and HLA DR/DQ typing by the PCR-sequence-specific oligonucleotide
      probes method. RESULTS: HLA-DRB1*04 and HLA-DQB1*0302 were found to be positive
      associated with the CIN 3/invasive squamous cell carcinomas subgroup, whereas HLA
      DRB1*13 and HLA-DQB1*02 were negatively associated with the same group, when
      comparing to the control group. CONCLUSIONS: The data support the hypothesis that
      HLA-DRB1*04 and HLA-DQB1*0302 may be considered risk factors for malignant
      progression, whereas HLA-DRB1*13 and HLA-DQB1*02 may have a protective role.
      Further studies with a larger group are needed to confirm these susceptibility
      and protective roles in disease progression in Argentine population.

PMID- 18820540
TI  - The accuracy of the Papanicolaou smear in the screening and diagnostic settings.
AB  - OBJECTIVE: We evaluated the performance of the Papanicolaou smear in screening
      and diagnostic settings. STUDY DESIGN: We analyzed Papanicolaou smear results of
      1,850 women recruited into a clinical trial to evaluate an emerging technology
      for the detection of cervical cancer. Screening and diagnosis groups were based
      on the history of previous Papanicolaou smear results. We calculated
      sensitivities, specificities, positive and negative likelihood ratios (LR+ and LR
      ), receiver operating characteristic curves, and areas under the receiver
      operating characteristic curve (AUC). RESULTS: In the screening group, by
      defining disease as cervical intraepithelial neoplasia (CIN) 2,3/cancer or worse
      and using high-grade squamous intraepithelial lesion (HSIL) as the test cutpoint,
      the AUC was 0.689, and the LR+ and LR- were 39.25 and 0.67, respectively. In the
      diagnosis group, the AUC was 0.764, and the LR+ and LR- were 3.79 and 0.56,
      respectively. By defining disease as human papillomavirus/CIN 1 or worse and HSIL
      as the test cutpoint, the AUC was 0.586, and the LR+ and LR- were 17.01 and 0.92
      in the screening group; in the diagnosis group, the AUC was 0.686, and the LR+
      and LR- were 2.77 and 0.75, respectively. CONCLUSIONS: In a screening setting, a
      Papanicolaou smear result of HSIL or worse is 39 times more likely in a patient
      with CIN 2,3/cancer than in a patient without it. This compares to 4 times more
      likely in the diagnostic setting. The magnitude of the positive likelihood ratio
      observed in the screening group indicated that abnormal Papanicolaou smear
      results obtained in the screening setting should have more impact on clinical
      decision making than those from results obtained in the diagnostic setting.

PMID- 18820541
TI  - Men's attitudes toward receiving the human papillomavirus vaccine.
AB  - OBJECTIVES: To determine men's attitudes toward receiving the human
      papillomavirus (HPV) vaccine. MATERIALS AND METHODS: Five hundred seventy-one men
      read a 1-page informational sheet about HPV and the HPV vaccine before completing
      a 29-item questionnaire. Descriptive statistics were calculated on all variables.
      RESULTS: Of these men, 33% wanted to receive the HPV vaccine, 27% did not, and
      40% were undecided. The main reasons for wanting the vaccine included a desire to
      stay healthy (67.4%); prevention of cancer in my sexual partner(s) (52.9%);
      prevention of anal, penile, and head and neck cancer (41.0%); fear of cancer
      (33.4%); and prevention of genital warts (32.8%). Being in a monogamous
      relationship and not at risk (18.9%), not interested (13.8%), and not enough
      evidence yet to prove that it will help men (8.2%) were the main reasons for not
      wanting to be vaccinated. CONCLUSIONS: Although many men want to receive the HPV
      vaccine, more remain undecided. Pending favorable safety and efficacy results
      from a clinical trial for men, substantial factual education will likely convince
      many ambivalent men to receive the HPV vaccine.

PMID- 18820542
TI  - Effect of cervicitis on visual inspection with acetic acid.
AB  - OBJECTIVE: The objective of this study was to determine whether the presence of
      cervicitis influenced the accuracy of visual inspection with acetic acid (VIA).
      MATERIALS AND METHODS: In a pilot study, 502 women from rural El Salvador were
      screened for cervical cancer using methods including colposcopy and VIA. The
      presence of cervicitis was assessed by grading the amount of inflammation on each
      woman's cervical biopsy. Data from 495 women found to be free of cervical
      neoplasia were analyzed for the present study. RESULTS: In this study population,
      74% of women were classified as having cervicitis. Both the result of visual
      inspection and the result of colposcopy were highly associated with the presence
      of cervicitis (p =.007 and p =.006, respectively). Women with cervicitis were
      twice as likely to have a positive VIA result as women without cervicitis (odds
      ratio = 2.0, 95% CI: 1.0-3.7). CONCLUSIONS: The presence of cervicitis may
      influence the accuracy of results obtained from colposcopy and VIA. This
      observation may be of particular importance in low-resource settings such as El
      Salvador where visual inspection methods are more commonly used in screening for
      cervical cancer.

PMID- 18820543
TI  - Prevalence of the human papillomavirus in an inner-city indigent population with
      previously normal Pap tests.
AB  - OBJECTIVE: To determine the prevalence of human papillomavirus (HPV) in our inner
      city indigent population (clinic population) of women with previously normal Pap
      tests and to identify any associated risk factors. MATERIALS AND METHODS: A
      prospective cohort of 187 women between the ages of 15 and 49 years, with
      previously normal Pap tests, was recruited from a university affiliated
      outpatient clinic. A demographic questionnaire of social and sexual history was
      elicited, and ThinPrep cytology (Cytyc, Marlborough, MA) and HPV Digene Hybrid
      Capture II results (Digine, Gaithersburg, MD) were obtained. RESULTS: The
      prevalence of HPV in our primarily Hispanic clinic population was 21%. The mean
      age of women with HPV was 28.9 years and those without were 32.1 years (p <.046).
      In women with HPV, 24% had abnormal Pap tests, whereas in those without HPV, 5%
      had abnormal Pap tests (p <.001). Women who were older and parous were less
      likely to have HPV (7.5%; p <.024). The presence of HPV was not influenced by
      sexual behaviors, sexually transmitted diseases, smoking, race, or contraceptive
      use. CONCLUSIONS: The prevalence of HPV in an inner-city indigent population,
      despite previously normal cytology, was consistent with earlier reported rates of
      HPV. Our data suggest that younger, nulliparous women have a high prevalence of
      HPV.

PMID- 18820544
TI  - Colposcopically observed vascular changes in the cervix in relation to the
      hormonal levels and menstrual cycle.
AB  - OBJECTIVE: We assessed colposcopically observed vascular changes occurring in the
      cervix in relation to cyclical hormonal variation in healthy women. MATERIALS AND
      METHODS: Thirty women with regular menstrual cycles and willing to remain
      sexually abstinent during a menstrual cycle were enrolled. Colposcopy was
      performed during the peak of the estrogen and progesterone levels. RESULTS: The
      mean (+/-SD) diameter of the largest visible blood vessel differed significantly
      between the estrogenic phase (0.38 +/- 0.14 mm) as compared with the
      progestogenic phase (0.47 +/- 0.12 mm; p <.01). The blood vessels were more
      prominent and dense and had a well-defined outline during the progestogenic phase
      than the estrogenic phase; however, these differences were not statistically
      significant. There was borderline increase in the interleukin 8 level during the
      estrogenic phase. CONCLUSIONS: Physiological changes of increased vascularity of
      the cervix observed colposcopically during the progestogenic phase are normal. If
      such changes do not correspond to the menstrual cycle phase in women using
      vaginal microbicides in early-phase clinical trials, presence of inflammatory
      markers should be evaluated. Elevated interleukin 8 during the estrogenic phase
      needs further evaluation.

PMID- 18820545
TI  - Assessment of follow-up for low-grade cytological abnormalities in the National
      Breast and Cervical Cancer Early Detection Program, 2000-2005.
AB  - OBJECTIVE: To assess the management of women in the National Breast and Cervical
      Cancer Early Detection Program with low-grade squamous intraepithelial lesions
      (LSIL) before and after the American Society for Colposcopy and Cervical
      Pathology (ASCCP) guidelines for management of abnormal cytology were published
      in 2002. MATERIALS AND METHODS: We examined the follow-up for 22,342 women with
      LSIL during 2 periods: 2000-2002 and 2003-2005. RESULTS: The percentage of
      providers who followed the recommended guidelines with colposcopy for an LSIL Pap
      test result increased by 9% from the pre-ASCCP to the post-ASCCP period. An
      increase was seen in every age and racial/ethnic group. Younger women (<30 years)
      and white women were more likely than comparison groups to be followed by
      colposcopy rather than a repeat Pap test. CONCLUSIONS: The increase in percentage
      of women having colposcopy in 2003, 1 year after the new guidelines were
      published, suggests a change in provider practices consistent with those
      guidelines.

PMID- 18820546
TI  - The prevalence of examiner-diagnosed clitoral hood adhesions in a population of
      college-aged women.
AB  - OBJECTIVE: To determine the prevalence of clitoral hood adhesions in college-aged
      women. MATERIALS AND METHODS: A retrospective review of medical records was
      conducted for 589 college-aged women undergoing a routine women's annual
      examination at a student health clinic by a single examiner (E.W.) using a
      standardized procedure. The severity of adhesions was classified and recorded by
      the examiner based on the extent of visualization of the clitoral glands and
      sulcus. Recorded age, sexual activity, contraceptive use, pregnancy, and marital
      status were abstracted from records. RESULTS: Two thirds (393/589) of women were
      unaffected by any clitoral hood abnormality; of the affected, 58% (113/196)
      showed 25% involvement. Only 12% (24/196) showed adhesions involving 75% to
      >or=90% of the region (chi2 = 857.1, 4 df, p <.0001). The youngest females, born
      after 1981, were at highest risk for being affected (compared with women born
      1976-1981, adjusted OR = 1.7 [1.1, 2.6]). Relationships with other demographic
      and behavioral characteristics were not statistically significant. CONCLUSIONS:
      Adhesions may be more common than previous published reports imply. Study
      participants were evaluated for routine health screening and presented with few
      or no symptoms. These data suggest that adhesions may be a normal variant in
      otherwise asymptomatic college-aged women and that no treatment is necessary.

PMID- 18820547
TI  - Assessing new technologies for cervical cancer screening: beyond sensitivity.
AB  - New technologies have been proposed to replace cervical cytology as the medium
      for cervical cancer screening, especially testing for human papillomavirus (HPV).
      Many of these alternatives have been endorsed because their single-test
      sensitivity is superior to that of cytology. The sensitivity of a single Pap test
      may be as low as 50%, but lifetime testing has significantly greater sensitivity,
      and other parameters are also important in defining the optimal screening test.
      Test accuracy depends not only on sensitivity but also on specificity and disease
      prevalence; both of these are problematic when considering HPV as a screen. A
      screening test also must be acceptable to both clinicians and patients. HPV
      testing is regarded as test for a sexually transmitted disease by many women.
      Clinicians often fail to appreciate the transient nature of HPV infection,
      prompting overly aggressive treatment that risks future preterm birth, and there
      is no consensus about strategies for follow-up of abnormal HPV screening results
      when obtained without concomitant cytology. An emphasis on sensitivity also may
      be inappropriate when most cervical cancers occur in unscreened women, for whom
      the sensitivity of testing is irrelevant. HPV testing and other technologies have
      substantial promise as tests that may replace cytology in cervical cancer
      screening, but obstacles are significant, and premature adoption of these methods
      may result in patient harm.

PMID- 18820548
TI  - Glomus tumor presenting as a periurethral mass.
AB  - OBJECTIVES: Glomus tumors, a neoplasm arising from the glomus body, usually occur
      in the extremities with a particular predisposition to a subungual site. Glomus
      tumors are exceedingly rare in the external genitalia. In this case, the origin
      of a periurethral mass proved to be a glomus tumor. MATERIALS AND METHODS: A 61
      year-old woman presented with postmenopausal vaginal bleeding. Clinical
      examination revealed a focally ulcerating, soft periurethral mass. A subsequent
      wedge biopsy of a periurethral, submucosal tumor was examined microscopically
      using both hematoxylin and eosin stains and an extensive immunohistochemical
      panel. RESULTS: The initial histopathologic differential diagnosis of the wedge
      biopsy included several neoplasms, but final analysis, including
      immunohistochemistry (vimentin, desmin, and calponin positivity), concluded that
      the lesion was a glomus tumor. CONCLUSIONS: Periurethral masses are rare and may
      be caused by a large number of neoplastic and nonneoplastic lesions. This case of
      glomus tumor presenting as a periurethral mass may be the only third reported
      occurrence.

PMID- 18820549
TI  - Journal of Lower Genital Tract Disease. Home study course: Fall 2008.

PMID- 18820550
TI  - We share the vision that we can make a difference in the protection of women from
      the devastating consequences of cervical and other lower genital tract cancers
      and diseases.

PMID- 18820552
TI  - Nurturing the next generation of healthcare professionals--whose job is it?

PMID- 18820554
TI  - Society of Trauma Nurses position statement on the role of the clinical nurse
      specialist in trauma.
AB  - The clinical nurse specialist (CNS) is included in the collective term advanced
      practice nurse. Preparation of the CNS involves completion of a graduate program
      with a clinical focus, specialty certification, and state-defined requirements
      for licensure.The trauma CNS demonstrates advanced clinical knowledge based on an
      in-depth understanding of the pathophysiology of trauma combined with extensive
      practical experience observing human responses to injury. The trauma CNS assumes
      the traditional subroles as expert practitioner, educator, consultant, and
      researcher with the proportion of time spent in each subrole based on the needs
      of the trauma program. The CNS's ability to minimize variances in care and
      prevent adverse outcomes directly support performance improvement. The Society of
      Trauma Nurses recognizes and supports the utilization of CNSs in trauma programs.

PMID- 18820555
TI  - Traumatic brain injuries sustained in the Afghanistan and Iraq wars.
AB  - OVERVIEW: When traumatic brain injury (TBI) occurs simultaneously with more
      obviously life-threatening wounds, it may go unrecognized. Civilians and military
      personnel working in or near combat zones are at risk for this injury. Blast
      related and closed-head injuries, rather than penetrating injuries, constitute
      the majority of TBIs in this population. The authors describe the experiences of
      the Defense and Veterans Brain Injury Center team at Walter Reed Army Medical
      Center in Washington, DC, and present a composite case to illustrate the nurse's
      role in the assessment and care of the TBI patient.

PMID- 18820557
TI  - Education and prevention for teens: using Trauma Nurses Talk Tough presentation
      with pretest and posttest evaluation of knowledge and behavior changes.
AB  - Injury prevention is an essential part of any trauma program. Trauma Nurses Talk
      Tough (TNTT) is an injury prevention program utilized at many trauma centers
      targeting school-aged children from kindergarten through 12th grade. We
      hypothesized that TNTT would increase knowledge of safety strategies and change
      behavior with a prospective, correlational study using TNTT for 6th- to 8th-grade
      (n = 372) and 9th- to 12th-grade (n = 158) students, respectively. The TNTT
      injury prevention program had an effect on all students of 6th to 12th grades;
      however, the effect was more pronounced in the 6th- to 8th-grade group.

PMID- 18820558
TI  - Managing rural emergency department overcrowding.
AB  - Emergency department visits reached more than 115 million in 2005, a 30% increase
      over the past decade. Although much has been written regarding these numbers,
      little attention has been focused on the impact of overcrowding and volume
      increases on rural emergency departments. Rural emergency departments face
      challenges unlike their urban counterparts that make implementation of current
      overcrowding strategies difficult or impossible. This article addresses these
      challenges and suggests strategies specific to the needs of rural emergency
      departments.

PMID- 18820559
TI  - Propofol infusion syndrome.
AB  - Propofol (Diprivan) is an intravenous sedative hypnotic that is used in the
      induction and maintenance of anesthesia and sedation. High-dose infusions have
      been associated with several serious adverse effects and, when combined, they are
      known as propofol infusion syndrome (PRIS). Although PRIS is rare, it is
      frequently fatal if not identified early. The purpose of this article is to raise
      practitioner awareness to this syndrome, with recommendations for early
      identification, prevention, and treatment of PRIS.

PMID- 18820560
TI  - Right ventricular gunshot wound with retrograde embolization.
AB  - There have been numerous reports concerning gunshot wounds to the heart over the
      years. Many reports discuss bullets that have embolized and have migrated
      antegrade. However, there has never been a case reported on the retrograde
      embolization of a bullet from the right ventricle into the inferior vena cava.
      This case report involves a 15-year-old boy who was accidentally shot in the
      chest. The bullet entered at the mid-manubrial area, and penetrated the anterior
      wall of the right ventricle causing a tamponade. A chest x-ray film confirmed a
      bullet in the right ventricle. The patient was stabilized in the emergency
      department, and taken to the operating room for an emergent mediastinal
      exploration with evacuation of pericardial tamponade and repair of the right
      ventricle. After the tamponade was relieved, a Trans-Esophageal Echocardiogram
      was performed to locate the bullet, which could not be found in the ventricle.
      Chest and abdominal radiography were performed to locate the bullet. X-ray films
      confirmed that the bullet had migrated retrograde down into the inferior vena
      cava. Interventional radiology and vascular surgery departments were consulted.
      The consensus was to snag the bullet under fluoroscopic guidance, and pull it
      down into the right femoral vein for easy retrieval. The chest was closed and the
      patient was transferred from the surgery department to the interventional
      radiology department. Under fluoroscopy, the bullet was pulled down into the
      right common femoral vein. The bullet was extracted per venorrhaphy. The patient
      was extubated within hours after surgery and discharged home within 72 hours of
      surgery.

PMID- 18820561
TI  - Early detection of posttraumatic stress disorder in children.
AB  - Surviving trauma patients are at an increased risk for developing posttraumatic
      stress disorder (PTSD) symptoms. An estimated 1 million American children develop
      some form (acute, chronic) of PTSD every year. The purpose of this study was to
      benchmark detection of PTSD in children at our trauma center against the national
      average and develop a guideline that would identify children who might need
      referral for screening prior to discharge. A collaborative effort among the
      trauma, rehabilitation, neuropsychology, and pediatric personnel resulted in a
      guideline to address early detection of PTSD in children. After implementation of
      the guideline, there was a 40% increase in detection of PTSD symptoms in
      identified children who were screened. We conclude that a systematic
      identification of PTSD triggers increases the detection rate of PTSD and
      opportunities for screening and intervention.

PMID- 18820562
TI  - Home hazards: can children recognize the dangers?
AB  - To have effective injury prevention programs for children, solid education must
      be provided. Initially, the parental responsibility includes protecting and
      instructing the child about dangerous situations. However, when children can
      recognize a hazard for themselves, this becomes the basis for behavior change
      according to the health belief model. For trauma centers providing injury
      prevention services, knowing what a child perceives as a safety issue can be
      instrumental in correctly targeting curriculum. The following is a compilation of
      responses of 90 children who participated in a 2008 Home Hazard Recognition
      Station at a local Safe Kids event.

PMID- 18820563
TI  - Creating an evidence-based practice environment: one hospital's journey.
AB  - There is increasing effort in promoting evidence-based practice (EBP) that
      supports the best possible care to patients and families. This article describes
      essential concepts for developing an environment of EBP and its implementation at
      a large pediatric hospital. Essential components for creating an EBP environment
      include vision, engagement, integration, and evaluation. An institutional
      initiative to decrease procedure-related pain demonstrates how EBP is used to
      improve clinical care.

PMID- 18820565
TI  - Core competencies for a trauma subspecialty nurse practitioner.
AB  - The role of a trauma nurse practitioner (TNP) is not a new one. Trauma facilities
      around the nation are continually finding ways to incorporate and expand upon the
      role of the TNP within their infrastructure to better utilize resources while
      simultaneously providing comprehensive care. While this is the case, there is a
      dearth of information on the core competencies required for a TNP to practice
      efficiently. Having concise information on the core competencies for a TNP will
      be of great benefit to graduate nurse practitioners as well as seasoned nurse
      practitioners looking to change specialties.

PMID- 18820568
TI  - Universal influenza vaccination and live attenuated influenza vaccination of
      children.
AB  - Influenza is an uncontrolled epidemic disease that is vaccine preventable. Each
      winter the peak of medically attended acute respiratory illness coincides with
      the peak of influenza virus activity. The anatomy of an urban influenza epidemic
      is presented highlighting the role of children in the spread of influenza. The
      efficacy and safety of the live attenuated influenza vaccine (LAIV) for children
      are documented and the indirect effectiveness (herd protection) of vaccinating
      schoolchildren is demonstrated. Children have the highest attack rates during
      influenza epidemics and the consequences of influenza virus infection can be
      severe regardless of the virus type--A(H1N1), A(H3N2), or B. Early in the
      epidemic, over one-half of the culture-positive illnesses will occur in school
      aged children demonstrating their role in spreading the virus in the community.
      LAIV has been shown to be superior to inactivated vaccine for children and is
      safe even for children with mild intermittent asthma. One dose of LAIV is
      effective and gives almost immediate protection. LAIV administered by nasal spray
      is readily accepted by children. Several studies have demonstrated herd
      protection by immunizing schoolchildren. These studies have shown that immunizing
      schoolchildren is more efficient than vaccinating elderly and high-risk patients
      directly. Current recommendations for influenza vaccine give priority to more
      than 200 million persons in the United States, but vaccine coverage has not
      improved since 1997. Systematic delivery of influenza vaccine in school-based and
      workplace-based clinics would greatly enhance the control of epidemic influenza
      and help prepare for the next pandemic.

PMID- 18820566
TI  - Fluid resuscitation in the trauma patient.
AB  - Trauma is responsible for 25% of all emergency department visits causing a
      healthcare burden of more than $400 billion a year. Timely and appropriate fluid
      resuscitation may mean the difference between survival and death. Controversy
      surrounds the best method of fluid resuscitation for optimum recovery. This
      article will evaluate current research regarding the various types of fluid
      resuscitation in the trauma population. Colloid and crystalloid fluid will be
      compared describing the risks and benefits of each.

PMID- 18820569
TI  - Antivirals and influenza: frequency of resistance.
AB  - Antivirals are effective in prophylaxis and therapy for influenza and are likely
      to be active against a new pandemic variant. They can be divided into the M2
      inhibitors, adamantane and rimantadine, and the neuraminidase inhibitors (NAIs),
      zanamivir and oseltamivir. The former are limited in activity to type A viruses,
      whereas the latter are also active against type B viruses. Both classes of drugs
      appear similarly efficacious in prophylaxis at approximately 70-90%. However, use
      of M2 inhibitors (adamantanes) in therapy is limited by side effects, more common
      with amantadine, and also by production of antiviral resistance and lack of
      demonstrated prevention of complications. The NAIs prevent both types of seasonal
      influenza, shorten duration of illness, and reduce complications. As such, their
      use for seasonal influenza treatment has been increasing. They are active against
      A(H5N1) but oseltamivir has been most extensively stockpiled because the
      infection in humans may be disseminated. Resistance does emerge, but not at the
      same frequency as with the M2 inhibitors. Resistant viruses also appear less fit
      and thus less able to spread. However, as use increases, resistance needs to be
      carefully monitored.

PMID- 18820570
TI  - Vaccines against pandemic influenza: what can be done before the next pandemic?
AB  - We currently do not know which specific influenza subtype or isolate will cause
      the next influenza pandemic. However, 4 influenza virus hemagglutinin subtypes
      (H2, H5, H7, and H9) are considered the most likely candidates. Avian influenza
      viruses of the H5N1 subtype have received the most attention to this point, as
      their ability to spread within the human population remains the only barrier to
      emergence of a pandemic strain. Several vaccines have been tested against these
      potential pandemic viruses using standard methods for developing inactivated
      vaccines. In general, these vaccines have been poorly immunogenic, requiring high
      doses and multiple exposures to generate even modest antibody titers. The use of
      adjuvants to improve presentation of antigen and stimulate the immune system
      offers promise for enhanced immunity. Currently approved adjuvants, MF59 and
      Alum, can be readily incorporated into pandemic vaccines, while novel adjuvants
      are moving toward approval, but may still be years away from routine use. Thus, a
      prepandemic vaccine strategy that involves the stockpiling of both potential
      antigens and proven adjuvants may represent the best approach to deal with this
      looming threat.

PMID- 18820571
TI  - RNA interference strategies as therapy for respiratory viral infections.
AB  - RNA interference (RNAi) is a recently discovered, naturally occurring
      intracellular process that regulates gene expression through the silencing of
      specific mRNAs. Methods of harnessing this natural pathway are being developed
      that allow the catalytic degradation of targeted mRNAs using specifically
      designed complementary small-interfering RNAs (siRNA). siRNAs are being
      chemically modified to acquire drug-like properties. Numerous recent high profile
      publications have provided proofs of concept that RNAi may be of therapeutic use.
      Much of the design of these siRNAs can be accomplished bioinformatically, thus
      potentially expediting drug discovery and opening new avenues of therapy for many
      uncommon, orphan, or emerging diseases. Although endogenous human disease targets
      can theoretically be affected by RNAi therapeutics, nonendogenous targets (eg,
      viral targets) are attractive and RNAi therapeutics have been shown to act as
      antivirals in vivo and in vitro. Respiratory viral infections are particularly
      attractive targets for RNAi therapeutics because the infected cells exist at the
      air-lung interface, thereby positioning these cells to be accessible to topical
      administration of siRNA, for example by aerosol. RNAi therapeutics have been
      shown to be active against respiratory syncytial virus, parainfluenza and
      influenza in vitro and in vivo resulting in profound antiviral effects. The first
      RNAi therapeutic to be designed as an anti-infective medication has now entered
      proof of concept clinical trials in man. A discussion of the science behind RNAi
      is followed by a presentation of the potential practical issues in applying this
      technology to respiratory viral diseases. RNAi may offer new strategies for the
      treatment of respiratory syncytial virus and other respiratory viruses.

PMID- 18820572
TI  - Current status of vaccines for parainfluenza virus infections.
AB  - Parainfluenza viruses (PIV) have been generally disregarded as pathogens in spite
      of their importance in pediatric lower respiratory illness. Because PIVs account
      for 17% of hospitalized illness associated virus isolation, the development of
      PIV vaccine would be a major advance in preventing lower respiratory tract
      infection in infants and young children. We will review in detail several PIV
      vaccine candidates and recent newer approaches to PIV vaccine development.
      Intranasally administered bovine PIV3 (bPIV3) vaccine and cold-adapted PIV3
      vaccine have been evaluated throughout the pediatric age spectrum. BPIV3 does not
      give a robust response to the heterotypic human strain although seroconversion
      rate to bPIV3 is 57-65%. However, bPIV3 vaccine is being used as an attenuated
      backbone for insertion of human PIV3 hemagglutinin-neuraminidase and fusion (F)
      proteins and a surface protein, F, of respiratory syncytial virus. The
      effectiveness of this vaccine against both PIV3 and RSV challenge has been
      demonstrated in African green monkeys. The cold-adapted PIV3 vaccine has been
      extensively evaluated and is safe and immunogenic in seronegative children with a
      seroconversion rate of 79%. These promising candidates deserve to enter into
      efficacy trials both for their ability to prevent PIV3 disease and as a model of
      protection against respiratory illness by mucosal vaccination.

PMID- 18820576
TI  - Proceedings of the 2007 International Congress on Respiratory Viruses, July 20
      22, 2007, Colorado Springs, Colorado, USA.

PMID- 18820573
TI  - Development of recombinant Sendai virus vaccines for prevention of human
      parainfluenza and respiratory syncytial virus infections.
AB  - Respiratory syncytial virus (RSV) and human parainfluenza viruses (hPIVs) are the
      most important causes of hospitalization for viral respiratory tract diseases in
      infants and young children. Unfortunately, there are currently no licensed
      vaccines for prevention of these infections. Researchers at St. Jude Children's
      Research Hospital are now developing Sendai virus (SV), a natural respiratory
      pathogen of mice, as a Jennerian vaccine for hPIV-1, and as a vaccine backbone
      for the prevention of RSV and other hPIVs. Unmodified SV is currently being
      tested in the clinic. Thus far, the vaccine has been well tolerated. Preclinical
      studies also continue and have demonstrated that intranasal vaccinations with
      recombinant SV expressing an RSV antigen are sufficient to activate high
      magnitude RSV-specific neutralizing B- and T-cell activities in a cotton rat
      system. Furthermore, vaccinated animals are completely protected against RSV
      challenges. As clinical safety studies progress, St. Jude Children's Research
      Hospital researchers are also working to formulate a SV-based cocktail vaccine
      designed to prevent several hPIV and RSV infections in humans.

PMID- 18820577
TI  - 2007 International Congress on Respiratory Viruses. Introduction.

PMID- 18820578
TI  - H5N1 transmission and disease: observations from the frontlines.
AB  - Avian influenza A (H5N1) viruses cause severe disease in humans, characterized by
      rapidly progressive pneumonia, multiorgan dysfunction, and high mortality. Poor
      clinical outcome is associated with high viral load in throat specimens and
      frequent detection of virus in feces and blood. The latter finding indicates the
      potential of the virus to disseminate in humans, similar to what occurs in
      mammals and birds, which is supported by evidence in autopsy studies of virus in
      extrapulmonary tissues such as liver and brain. Beside direct virus-induced
      tissue damage, an intense inflammatory response to the virus likely contributes
      to disease pathogenesis. In vitro and animal experiments showed that H5N1 viruses
      induce cytokine production in macrophages and respiratory epithelium. In
      accordance, human H5N1 infections are characterized by increased plasma chemokine
      and cytokine concentrations, the levels of which correlate with pharyngeal virus
      load and clinical outcome. Although antiviral therapy forms the mainstay of
      treatment, the impact of oseltamivir on H5N1-associated mortality seems limited
      so far. Explanations for this include late institution of treatment, suboptimal
      dosing and drug delivery, and development of drug resistance, the latter of which
      may not be a rare event. The focus of clinical management should be on preventing
      virus and immune-mediated damage by early diagnosis and effective antiviral
      treatment with regimens, preferably parenteral, that minimize the risk of
      resistance development.

PMID- 18820579
TI  - Preparing for the next influenza pandemic.
AB  - There are 3 requirements for an influenza virus to cause a pandemic. It must be
      antigenically novel, cause severe disease, and transmit easily from human to
      human. Highly pathogenic avian influenza viruses of the H5N1 subtype currently
      circulating in bird populations in Asia, Africa, and Europe have met 2 of these
      criteria, and there is significant concern that these viruses will be the cause
      of the next pandemic. International efforts to prepare for a possible pandemic
      are underway. Priorities for pandemic planning include surveillance of influenza
      viruses in wild bird populations and at the avian-human interface, research into
      factors affecting the pathogenicity of these strains, stockpiling effective
      antivirals for use as a stopgap until an appropriate vaccine can be developed and
      distributed, and gaining an improved understanding of the utility of
      nonpharmaceutical interventions to slow or prevent the spread of these viruses
      within humans. Although considerable progress has been made in recent years
      towards readying the world for such an event, there is more work to be done.
      Physicians and hospitals can begin by educating themselves on the problem and
      developing a pandemic plan for their own practice or organization.

PMID- 18820580
TI  - Respiratory syncytial virus persistence: evidence in the mouse model.
AB  - Several studies have described a clear association between respiratory syncytial
      virus (RSV) lower respiratory tract infection in infancy and the subsequent
      development of persistent wheezing in children. Using the mouse model we
      demonstrated that RSV induces long-term airway disease characterized by chronic
      airway inflammation and airway hyperreactivity (AHR). The RSV murine model offers
      great advantages to study the immunopathogenesis of RSV-induced long-term airway
      disease. Mice can be challenged with aerosolized methylcholine to determine the
      presence of AHR. We can apply the reverse transcription-polymerase chain reaction
      assay (RT-PCR) to detect RSV RNA in the respiratory tract and we can perform lung
      gene expression analysis to further characterize the chronic changes induced by
      RSV infection. Compared with sham-inoculated controls, RSV-infected mice
      developed chronic airway disease characterized by AHR and persistent airway
      inflammation. Forty-two days after RSV infection, a time point when RSV could no
      longer be isolated, RT-PCR demonstrated, quite unexpectedly, the presence of RSV
      RNA in the lower respiratory tract of mice. The presence of genomic RNA persisted
      for months after inoculation. Furthermore, preliminary studies also demonstrated
      that on day 42 there were a number of genes differentially expressed in RSV
      infected mice compared with controls. RSV-infected mice with persistent AHR
      exhibited presence of abnormal chronic inflammatory changes, altered gene
      expression profiles, and persistence of RSV RNA, which may contribute to long
      term airway disease induced by RSV. Future studies are needed to define the
      significance of persistent RSV RNA in the mouse model, and its potential role in
      the pathogenesis of RSV-induced persistent wheezing in children.

PMID- 18820581
TI  - Respiratory syncytial virus persistence in chronic obstructive pulmonary disease.
AB  - Respiratory syncytial virus (RSV) is predominantly recognized as a pediatric
      pathogen although sensitive molecular diagnostic techniques have led to its more
      frequent detection in some adult settings. In some studies RSV has been detected
      just as frequently in stable chronic obstructive pulmonary disease (COPD)
      patients as in those suffering disease exacerbations, leading to the suggestion
      that RSV may persist in COPD. Although some studies have found negligible RSV in
      stable COPD, others have detected RSV in one-quarter to one-third of stable COPD
      samples. Possible reasons for this discrepancy are explored within the article. A
      relationship between RSV detection and increased disease severity, including rate
      of decline in lung function and systemic/airway inflammation, has been found on
      both occasions it has been sought. Susceptibility to persistent RSV infection
      could involve both host and viral factors. Cigarette smoking and COPD are likely
      to result in impaired antiviral immunity, and RSV is capable of evading immune
      responses by inducing skewed type 2 T-helper cell responses, antagonizing
      antiviral cytokines, mimicking chemokines, inhibiting apoptosis, and entering
      immune-privileged cells such as pulmonary neurons. It can also escape an
      established immune response through antigenic drift. This article examines
      current evidence regarding persistence of RSV in COPD and its possible
      mechanisms. We also discuss various roles for RSV persistence in COPD
      pathogenesis. Further elucidation of the contribution of persistent RSV to the
      pathogenesis of COPD requires interventional studies. Persistence of RSV in COPD
      may have direct relevance to the pathogenesis of childhood diseases such as
      postbronchiolitic wheeze and asthma.

PMID- 18820582
TI  - New respiratory viruses of humans.
AB  - Acute respiratory viruses are a major cause of morbidity and mortality in humans
      worldwide and most acute respiratory infections are caused by viruses. Many of
      these viruses cause the highest burden of disease in specific risk groups such as
      young infants, the elderly, and immune-compromised individuals. Although the most
      important respiratory viruses of humans have been identified in the last century,
      in the past decade about a dozen "new" viruses have been discovered that may
      cause a high burden of acute respiratory disease in humans. Not only viruses were
      discovered that must have been with humans for many decades or centuries, such as
      human metapneumovirus and 2 different human coronaviruses, but also viruses that
      are truly new for humans and have emerged as a result of recent interspecies
      transmissions from other mammalian or avian reservoirs. The latter include highly
      pathogenic avian influenza viruses, severe acute respiratory syndrome (SARS)
      coronavirus, and Nipah virus. The discovery, etiologic role, and burden of
      disease caused by these infections are described.

PMID- 18820583
TI  - Mumps epidemiology and immunity: the anatomy of a modern epidemic.
AB  - The success of the measles, mumps, and rubella 2-dose vaccination program led
      public health officials in 1998 to set a goal to eliminate endemic transmission
      of mumps virus by 2010 in the United States. The large outbreak of mumps in the
      spring of 2006 has led public health officials to re-evaluate this goal and to
      recognize that the transmission and epidemiology of mumps in highly vaccinated
      populations may be different than anticipated. During 2006, a total of 6584
      confirmed and probable cases of mumps were reported to the Centers for Disease
      Control and Prevention and most of these, 5865, occurred between January 1 and
      July 31. The peak of the outbreak was in April and seemed to be focused on
      college campuses in 9 midwestern states with Iowa having the highest attack rate.
      College campuses with mumps outbreaks included ones with 77% to 97% of students
      having had 2 doses of a mumps vaccine. Diagnosing mumps proved to be problematic
      in vaccinated persons (ie, laboratory tests seemed to be insensitive and some
      apparent mumps cases had mild nonclassic illness). The outbreak demonstrated that
      mumps can sometimes transmit efficiently in highly vaccinated populations and the
      clinical and laboratory diagnosis of mumps in vaccinated persons is more
      difficult than in naive persons. The reason for this mumps outbreak is not clear
      but probably results from multiple factors contributing to an overall increase in
      susceptibility and/or transmission.

PMID- 18820584
TI  - Human metapneumovirus infection in adults.
AB  - Human metapneumovirus (hMPV) was first identified in 2001 in Dutch children with
      bronchiolitis. The virus is an RNA virus in the Pneumovirinae subfamily and is
      most closely related to respiratory syncytial virus. hMPV has been shown to have
      worldwide circulation with nearly universal infection by age 5. Similar to
      influenza and respiratory syncytial virus, activity is greatest during the winter
      in temperate climates. Most of the available data on the clinical manifestations
      of hMPV infection are from studies of children where the virus causes upper
      respiratory tract infections, bronchiolitis, and pneumonia. Reinfections with
      hMPV occur throughout adult life and hMPV infection has been documented in 1-9%
      of adults each year using RT-PCR and serology for diagnosis. Illness is generally
      mild in young adults with serologic evidence of asymptomatic infection in many
      cases. Adults at highest risk of serious sequelae as a result of hMPV include the
      elderly, adults with underlying pulmonary disease, and those who are
      immunocompromised. Outbreaks of hMPV have been documented in long term care
      facilities with mortality of up to 50% in frail elderly residents. In addition, 6
      12% of exacerbations of chronic obstructive pulmonary disease have been
      associated with hMPV and underlying lung disease is common in patients
      hospitalized with hMPV. Lastly, hMPV has been linked with severe idiopathic
      pneumonia in recipients of hematopoietic stem cell transplants. Although the true
      spectrum of adult hMPV remains to be defined, it is clear that hMPV can result in
      severe illness the frail elderly and adults with underlying diseases.

PMID- 18820585
TI  - The pathogenesis of measles revisited.
AB  - Measles continues to be an important cause of childhood mortality in developing
      countries. The causative agent, measles virus (MV), is a member of the family
      Paramyxoviridae, genus Morbillivirus, and is spread via the respiratory route. MV
      was originally thought to enter the host by infecting epithelial cells of the
      respiratory tract, followed by viremia mediated by infected monocytes. However,
      neither of these cell types express signaling lymphocyte activation molecule
      (SLAM, CD150), which has been identified as the main receptor for wild-type MV.
      Measles has a relatively long incubation time, which makes it difficult to study
      the early stages of MV infection in humans. The animal models that best reflect
      the pathogenesis of measles are based on nonhuman primates. The use of
      recombinant MV strains expressing fluorescent proteins has greatly facilitated
      studies on viral tropism in macaques. These studies indicate that dendritic cells
      and lymphocytes expressing CD150 are the primary target cells for MV infection.
      At late stages of the infection MV also infects epithelial cells, despite the
      fact that these do not express CD150. Whether these cells express an as yet
      unidentified additional MV receptor remains unclear. On basis of these data it
      could be envisaged that dendritic cells are the first target cells for MV
      infection. These antigen-presenting cells may traffic the virus to the regional
      lymph nodes where they can transmit the virus to lymphocytes, which during
      viremia disseminate the virus throughout the body.

PMID- 18820586
TI  - Lung dendritic cells in respiratory syncytial virus bronchiolitis.
AB  - Respiratory syncytial virus (RSV) bronchiolitis, an important respiratory disease
      in infancy, is thought to be caused by severe inflammation of the small
      peripheral airways and has been associated with the development of recurrent
      wheeze, childhood asthma, and early allergen sensitization. Both innate and
      adaptive immune responses are thought to contribute to the development of
      bronchiolitis in RSV infection. If vaccination and specific therapy for
      bronchiolitis, which are currently lacking, are to be developed, detailed
      understanding of the immune responses involved is essential. Dendritic cells
      (DCs) are uniquely positioned to link innate to adaptive immune responses and may
      therefore be central to the development of bronchiolitis. In murine models,
      plasmacytoid DCs are recruited to the lung early in infection, presumably from
      the bone marrow, whereas lung myeloid DCs increase in numbers later in infection,
      with the advent of inflammation, and are derived from local lung precursors.
      Plasmacytoid DCs limit viral replication and they may have additional regulatory
      properties controlling pulmonary inflammation and lung function changes during
      bronchiolitis. In contrast, lung myeloid DCs are likely to contribute to
      inflammation during and after bronchiolitis and they may also facilitate
      sensitization to allergens. Myeloid DCs mature upon RSV infection and become
      potent activators of naive T cells, whereas in healthy lungs they are mostly
      immature and unable to stimulate naive T cells. As central players in the
      induction of adaptive immune responses, lung DCs need to be considered as targets
      for novel therapies and vaccination approaches.

PMID- 18820587
TI  - Respiratory syncytial virus and influenza virus infections: observations from
      tissues of fatal infant cases.
AB  - Respiratory syncytial virus (RSV) and influenza virus are common causes of
      infantile lower respiratory tract infection (LRTI). It is widely believed that
      both viral replication and inappropriately enhanced immune responses contribute
      to disease severity. In infants, RSV LRTI is known to be more severe than
      influenza virus LRTI. We compared cytokines and chemokines in secretions of
      infants surviving various forms of respiratory illness caused by RSV or influenza
      viruses, to determine which mediators were associated with more severe illness.
      We analyzed lung tissue from fatal cases of RSV and influenza LRTI to determine
      the types of inflammatory cells present. Quantities of lymphocyte-derived
      cytokines were minimal in secretions from infants with RSV infection.
      Concentrations of most cytokines were greater in influenza, rather than RSV,
      infection. Lung tissues from fatal RSV and influenza LRTI cases demonstrated
      extensive presence of viral antigen and a near absence of CD8-positive
      lymphocytes and natural killer cells, with marked expression of markers of
      apoptosis. Severe infantile RSV and influenza virus LRTI is characterized by
      inadequate (rather than excessive) adaptive immune responses, robust viral
      replication and apoptotic crisis.

PMID- 18820590
TI  - Community-associated methicillin-resistant Staphylococcus aureus: epidemiology
      and update.

PMID- 18820588
TI  - Viral respiratory infection and the link to asthma.
AB  - Viral respiratory infections are closely associated with wheezing illnesses and
      exacerbations of asthma throughout childhood, and yet there are a number of
      remaining questions pertaining to the specific nature of this relationship.
      Infection with an expanding list of respiratory viruses is an important cause of
      acute wheezing in infancy, and viruses are detected in most exacerbations of
      asthma throughout childhood. Furthermore, infants who develop severe viral
      respiratory infections are more likely to have asthma later in childhood. There
      has been progress in understanding the pathogenesis of viral respiratory
      illnesses, and this has led to new insights into how these processes might differ
      in asthma. Several host factors, including respiratory allergy and virus-induced
      interferon responses, modify the risk of virus-induced wheezing. In the absence
      of effective antiviral therapies, treatment of virus-induced wheezing and
      exacerbations of asthma can be challenging, and studies evaluating current
      treatment strategies are reviewed. Understanding the host-pathogen interactions
      that determine the severity of respiratory illnesses and long-term sequelae is
      likely to be of great help in identifying at-risk individuals, and in designing
      new and more effective treatments.

PMID- 18820591
TI  - MRSA: screening and laboratory identification.

PMID- 18820592
TI  - Effect of one-week treatment with vaginal estrogen preparations on serum estrogen
      levels in postmenopausal women.
AB  - OBJECTIVE: Approximately 50% of postmenopausal women suffer from vaginal atrophy,
      and a large proportion of them choose intravaginal estrogen preparations
      administered for local action to avoid systemic exposure to estrogens and its
      associated risk of breast and uterine cancer. The primary objective of this study
      was the evaluation of the systematic bioavailability of estradiol and estrone and
      the pharmacokinetics of two of the most frequently used intravaginal estrogen
      preparations, namely Vagifem and Premarin cream. DESIGN: While immunobased assays
      could not previously provide accurate measurement of serum estrogen
      concentrations in postmenopausal women, we have used validated mass spectrometry
      assays to measure the pharmacokinetics of serum estradiol and estrone during the
      24 hours following the seventh daily application of 25 microg estradiol (Vagifem)
      and 1 g (0.625 mg) conjugated estrogens (Premarin) cream in 10 postmenopausal
      women in each group. RESULTS: Serum estradiol was increased on average by 5.4
      fold from 3 to 17 pg/mL during the 24-hour period after daily administration of
      25 microg estradiol or 1 g (0.625 mg) conjugated estrogens cream. Serum estrone,
      conversely, increased 150% with Vagifem and 500% with Premarin cream.
      CONCLUSIONS: The present data using validated, accurate, and sensitive mass
      spectrometry assays of estrogens show that the Vagifem pill and Premarin cream,
      after 1 week of daily treatment, cause an approximately fivefold increase in
      serum estradiol in postmenopausal women, thus indicating that the effects are
      unlikely to be limited to the vagina and that systemic actions are expected after
      application of these intravaginal estrogen preparations.

PMID- 18820593
TI  - Thiopurine S-methyltransferase pharmacogenetics: autophagy as a mechanism for
      variant allozyme degradation.
AB  - OBJECTIVE: Thiopurine S-methyltransferase (TPMT)*3A is degraded much more rapidly
      than is the 'wild-type' enzyme through a ubiquitin-proteasome-dependent process.
      It also forms aggresomes, suggesting a possible dynamic balance between
      degradation and aggregation. We set out to identify genes encoding proteins
      participating in these processes. METHODS: Green fluorescent protein tagged
      TPMT*3A was expressed in a Saccharomyces cerevisiae gene deletion library, and
      flow cytometry was used to screen for cells with high fluorescence intensity,
      indicating the loss of a gene essential for TPMT*3A degradation. RESULTS: Twenty
      four yeast genes were identified in functional categories that included ubiquitin
      dependent protein degradation, vesicle trafficking, and vacuolar degradation. The
      presence of genes encoding proteins involved in vesicular transport and vacuolar
      degradation suggested a possible role in TPMT*3A degradation for autophagy--a
      process not previously identified as a pharmacogenomic mechanism. In support of
      that hypothesis, TPMT*3A aggregates increased dramatically in mutants for
      vacuolar protease and autophagy-related genes. Furthermore, TPMT*3A expression in
      human cells induced autophagy, and small interfering RNA-mediated knockdown of
      ATG7, an autophagy-related human protein, enhanced TPMT*3A aggregation but not
      that of TPMT*3C or wild-type TPMT, indicating that autophagy contributes to
      TPMT*3A degradation in mammalian cells. We also demonstrated that UBE2G2, the
      human homologue of the E2 ubiquitin-conjugating enzyme identified during the
      yeast genetic screen, was involved in TPMT*3A degradation in human cells.
      CONCLUSION: These results indicate that autophagy should be considered among
      mechanisms responsible for the effects of pharmacogenetically significant
      polymorphisms that alter encoded amino acids.

PMID- 18820594
TI  - Mitochondrial tRNAThr G15927A mutation may modulate the phenotypic manifestation
      of ototoxic 12S rRNA A1555G mutation in four Chinese families.
AB  - OBJECTIVE: To investigate the role of mitochondrial modifiers in the development
      of deafness associated with 12S rRNA A1555G mutation. METHODS: Four Chinese
      families with nonsyndromic and aminoglycoside-induced deafness were studied by
      clinical and genetic evaluation, molecular and biochemical analyses of
      mitochondrial DNA (mtDNA). RESULTS: These families exhibited high penetrance and
      expressivity of hearing impairment. Penetrances of hearing loss in WZD31, WZD32,
      WZD33, and WZD34 pedigrees ranged from 50 to 67% and from 39 to 50%,
      respectively, when aminoglycoside-induced hearing loss was included or excluded.
      Matrilineal relatives in these families developed hearing loss at the average of
      14, 13, 16, and 15 years of age, respectively, when aminoglycoside-induced
      deafness was excluded. Mutational analysis of entire mtDNA in these families
      showed the homoplasmic A1555G mutation and distinct sets of variants belonging to
      haplogroup B5b1. Of these, the tRNA G15927A mutation locates at the fourth base
      in the anticodon stem (conventional position 42) of tRNA. A guanine (G42) at this
      position of tRNA is highly conserved from bacteria to human mitochondria. The
      lower levels and altered electrophoretic mobility of tRNA were observed in cells
      carrying A1555G and G15927A mutations or only G15927A mutation but not cells
      carrying only A1555G mutation. The abolished base pairing (28C-42G) of this tRNA
      by the G15927A mutation caused a failure in tRNA metabolism, worsening the
      mitochondrial dysfunctions altered by the A1555G mutation. CONCLUSION: The
      G15927A mutation has a potential modifier role in increasing the penetrance and
      expressivity of the deafness-associated 12S rRNA A1555G mutation in those Chinese
      pedigrees.

PMID- 18820595
TI  - Molecular investigation of the functional relevance of missense variants of ICAM
      1.
AB  - In genome-wide studies, the intercellular adhesion molecule-1 (ICAM-1) locus has
      been associated with cardiovascular and inflammatory bowel diseases. To determine
      the functional relevance of five missense ICAM-1 variants (G241R; I316V; P352L;
      K469E; R478W), we generated wild-type and variant proteins [M2(241R); M3(469E);
      M4(352L); M5(478W); M6(316V); M7(352L/469E)] and transiently transfected CV1
      cells. Reverse transcription PCR, western blot, and ELISA did not reveal any
      differences in mRNA and protein expression levels for any construct. Conversely,
      in pulse-chase experiments, compared with wild-type (90-120 min), M3 and M5
      possessed a prolonged half-life of approximately 150 min, whereas M2, M4, and M7
      displayed a decreased half-life of approximately 60-75 min, implying differences
      in protein degradation. Our results do not indicate a major impact of missense
      variants on ICAM-1 biological function, even if G241R and K469E were functional
      in pulse-chase experiments. Whether these differences in protein stability exert
      measurable functional consequences needs to be elucidated further.

PMID- 18820596
TI  - Interethnic differences in drug metabolism.

PMID- 18820597
TI  - Hemoglobin substitutes.

PMID- 18820598
TI  - The optimal duration of adjuvant hormonal therapy for early-stage breast cancer.

PMID- 18820599
TI  - Monitoring treatment results in patients with chronic myelogenous leukemia.

PMID- 18820600
TI  - Single-dose recombinant activated factor VII for the treatment of joint bleeds in
      hemophilia patients with inhibitors.
AB  - Increasing evidence suggests that a single dose of 270 microg/kg recombinant
      activated factor VII (rFVIIa) may be a convenient, safe, and effective
      alternative to the repeat-dose regimen for hemophilia patients with inhibitors.
      Three recent trials investigating on-demand treatment (Kavakli et al 2006,
      Santagostino et al 2006, and Young et al 2008) lend further weight to earlier
      reports demonstrating that a single dose of 270 microg/kg rFVIIa is as effective
      as a repeat-dose schedule of 3 x 90 microg/kg rFVIIa in producing hemostasis,
      reducing the need for additional hemostatic medications, and improving pain and
      mobility in joints affected by hemarthroses. The single-dose regimen is
      advantageous as it may reduce both the difficulties caused by the need for
      repeated venous access and the interruption of daily activities associated with
      repeat dosing. Safety data from these three trials, along with those from a
      fourth study investigating the prophylactic use of 270 microg/kg rFVIIa, also
      demonstrate no additional or altered safety profile associated with single-dose
      treatment. These findings suggest that a single dose of 270 microg/kg rFVIIa is
      as safe and effective a hemostatic regimen as the standard lower, more frequent
      dose regimen and provides comparable bleeding control in hemophilia patients with
      inhibitors. The single-dose 270 microg/kg rFVIIa regimen utilized similar product
      consumption to the 3 x 90 microg/kg rFVIIa treatment regimen.

PMID- 18820601
TI  - Idiopathic hemophagocytic syndrome with a fulminant clinical course.

PMID- 18820602
TI  - Healing hemophagocytic syndrome in adults: the challenge continues.

PMID- 18820604
TI  - Oropharyngeal cancer.
AB  - Carcinoma of the oropharynx is of squamous histology in over 90% of cases.
      Oropharyngeal squamous cell carcinoma (OSCC) displays significant heterogeneity
      in terms of etiology, biology, and clinical behavior. It has now become clear
      that a subset is initiated by infection with high-risk human papillomavirus (HPV)
      types, especially type 16. This review summarizes the epidemiology, clinical
      presentation, molecular pathogenesis, diagnosis, and therapy of OSCC, focusing on
      the HPV-associated cases; it also details the need for a better understanding of
      the molecular pathogenesis of the different types of OSCC in order to improve
      treatment.

PMID- 18820605
TI  - Trading environments.

PMID- 18820606
TI  - Mistaken diagnosis.

PMID- 18820607
TI  - Rubber dam purpose.

PMID- 18820608
TI  - Commissioning appliances.

PMID- 18820609
TI  - Discriminatory.

PMID- 18820610
TI  - Unintentional oversight.

PMID- 18820611
TI  - Denture ulcerations.

PMID- 18820612
TI  - Sainsbury's launches dental services.

PMID- 18820621
TI  - Access to special care dentistry, part 7. Special care dentistry services:
      seamless care for people in their middle years--part 1.
AB  - Children and older people have been relatively well served by specialist dental
      care. Despite increasing disability amongst people in their middle years, there
      have been no or few dedicated dental teams with responsibility for provision of
      their oral care. This article explores the ethos and practicality of seamless
      care across the age groups and the primary/secondary care interface, with a focus
      on embedding oral health into general healthcare plans through the
      multidisciplinary team approach. The article explores four conditions--rheumatoid
      arthritis, Huntingdon's disease, multiple sclerosis and diabetes. It considers
      the features of each condition and how they can impact on both oral health and
      the delivery of dental services. It also considers the elements of care that
      contribute to a holistic and seamless approach to oral care services.

PMID- 18820622
TI  - The use of the erbium yttrium aluminium garnet (2,940 nm) in a laser-assisted
      apicectomy procedure.
AB  - If conventional endodontic treatment is not possible or not successful, apical
      endodontic surgery may be indicated. New techniques, materials and technologies
      have been used to increase the already high success rate of root canal treatment.
      The purpose of this article is to describe the use of the Erbium:YAG (2,940 nm)
      laser in treatment of apicectomy as a central tool, with the advantages of
      enhanced patient comfort, better bactericidal and decontamination effects.

PMID- 18820629
TI  - An infective endocarditis audit illustrates why dental guidelines in general need
      to be kept clear, simple and unambiguous.
AB  - OBJECTIVE: To test the effect complex, multiple dental guidelines have on
      establishing compliance with ideal clinical practice. DESIGN: A questionnaire was
      used to determine the level of knowledge of the British Cardiac Society and Royal
      College of Physicians 2004 infective endocarditis prophylaxis guidelines which
      were contemporary at the time the study was initiated, as well as to identify the
      existence of any written departmental policies on the safe management of patients
      at risk of developing this disease. SETTING: Hospital Orthodontic Departments in
      the East of England. SUBJECTS AND METHODS: Fourteen consultant and nine training
      grade group hospital orthodontists in the East of England initially answered the
      questionnaire in November 2005. The results of the survey were then discussed at
      a subsequent regional audit meeting after which standards were agreed. The
      original questionnaire was then reissued in June 2006 to 13 and eight of the
      original consultants and training grade group orthodontists respectively. This
      was coincidently three months after the publication of further new infective
      endocarditis prophylaxis guidance from the working party of the British Society
      for Antimicrobial Chemotherapy. RESULTS: The initial results indicated a number
      of significant deficiencies in the knowledge of which dental procedures either
      did or did not need antibiotic prophylaxis that the subsequent audit then
      improved to a variable extent. Nevertheless, the general finding was one of
      persistent confusion regarding the multiple conflicting contemporaneous
      guidelines. This lends further support to the concept of converging guidelines
      which remain disunified, complex and non-evidence based. CONCLUSIONS: The results
      of this audit confirm that compliance with preferred clinical practice is
      noticeably compromised when complex conflicting guidelines from either different
      national or international authoritative bodies exist for the same condition. With
      particular regard to the dental guidance for infective endocarditis prophylaxis,
      this has now been largely circumvented in the United Kingdom by the publication
      of a single, unambiguous guideline from the National Institute of Health and
      Clinical Excellence (NICE) in March 2008.

PMID- 18820643
TI  - Silencing of membrane-associated sialidase Neu3 diminishes apoptosis resistance
      and triggers megakaryocytic differentiation of chronic myeloid leukemic cells
      K562 through the increase of ganglioside GM3.
AB  - In chronic myeloid leukemia K562 cells, differentiation is also blocked because
      of low levels of ganglioside GM3, derived by the high expression of sialidase
      Neu3 active on GM3. In this article, we studied the effects of Neu3 silencing (40
      70% and 63-93% decrease in protein content and activity, respectively) in these
      cells. The effects were as follows: (a) gangliosides GM3, GM1, and
      sialosylnorhexaosylceramide increased markedly; (b) cell growth and
      [(3)H]thymidine incorporation diminished relevantly; (c) as mRNA, cyclin D2, and
      Myc were much less expressed, whereas cyclin D1 was expressed more like its
      inhibitor p21; (d) as mRNA, pro-apoptotic proteins Bax and Bad increased with
      concurrent decrease and increase in the anti-apoptotic proteins Bcl-2 and Bcl-XL,
      respectively; (e) the apoptosis inducers etoposide and staurosporine were active
      on Neu3 silencing cells but not on mock cells; (f) as mRNA, the megakaryocytic
      markers CD10, CD44, CD41, and CD61 increased similar to the case of mock cells
      stimulated with PMA; (g) the signaling cascades mediated by PLC-beta2, PKC, RAF,
      ERK1/2, RSK90, and JNK were largely activated. The induction of a GM3-rich
      ganglioside pattern in K562 cells by treatment with brefeldin A elicited a
      phenotype similar to that of Neu3 silencing cells. In conclusion, upon Neu3
      silencing, K562 cells show a decrease in proliferation, propensity to undergo
      apoptosis, and megakaryocytic differentiation.

PMID- 18820644
TI  - TLR4/MYD88-dependent, LPS-induced synthesis of PGE2 by macrophages or dendritic
      cells prevents anti-CD3-mediated CD95L upregulation in T cells.
AB  - Antigen-presenting cells (APCs) control T-cell responses by multiple mechanisms,
      including the expression of co-stimulatory molecules and the production of
      cytokines and other mediators that control T-cell proliferation, survival and
      differentiation. Here, we demonstrate that soluble factor(s) produced by Toll
      like receptor (TLR)-activated APCs suppress activation-induced cell death (AICD).
      This effect was observed in non-stimulated APCs, but it was significantly
      increased after lipopolysaccharide (LPS) treatment. Using different KO mice, we
      found that the LPS-induced protective factor is dependent on TLR4/MyD88. We
      identified the protective factor as prostaglandin E(2) (PGE(2)) and showed that
      both APC-derived supernatants and PGE(2) prevented CD95L upregulation in T cells
      in response to TCR/CD3 stimulation, thereby avoiding both AICD and activated T
      cell killing of target macrophages. The PGE(2) receptors, EP2 and EP4, appear to
      be involved since pharmacological stimulation of these receptors mimics the
      protective effect on T cells and their respective antagonists interfere with the
      protection induced by either APCs derived or synthetic PGE(2). Finally, the
      engagement of EP2 and EP4 synergistically activates protein kinase A (PKA) and
      exchange protein directly activated by cAMP pathways to prevent AICD. Taken
      together, these results indicate that APCs can regulate T-cell levels of CD95L by
      releasing PGE(2) in response to LPS through a TLR4/MyD88-dependent pathway, with
      consequences for both T cell and their own survival.

PMID- 18820645
TI  - Connexin 43 hemichannels contribute to the propagation of apoptotic cell death in
      a rat C6 glioma cell model.
AB  - Gap junctions (GJs) have been demonstrated to communicate cell death signals from
      apoptotic to healthy cells, thereby spatially extending apoptosis. Before being
      incorporated into GJs, hemichannels (hemi-GJs) are normally closed but recent
      evidence suggests that they can be opened by various messengers and conditions,
      thereby forming a pore through which molecules can enter or leave the cell
      potentially leading to cell death. The aim of this study was to determine the
      contribution of GJs and hemichannels in the communication of apoptosis toward
      surrounding cells. We induced apoptosis in C6 glioma cells stably transfected
      with connexin (Cx)43, with cytochrome C (cytC) using in situ electroporation and
      found that healthy surrounding cells underwent apoptotic transformation. Work
      with various cell death markers, wild-type (WT) and Cx43-expressing cells,
      inhibitors of GJs and/or hemichannels, and Cx43 gene silencing showed that GJs
      contribute to the spread of apoptosis in a zone next to where apoptosis was
      triggered whereas hemichannels also promoted cell death beyond this area.
      Buffering cytoplasmic Ca(2+) changes inhibited the spread of apoptosis in both
      cases. We conclude that Cx43 hemichannels, in concert with their GJ counterparts,
      play a role in communicating cytC-induced apoptotic cell death messages.

PMID- 18820646
TI  - Novel cell death by downregulation of eEF1A1 expression in tetraploids.
AB  - When duplicated sister chromatids are not properly compacted in mitosis,
      chromosomes are mis-segregated, inducing genetically unstable tetraploidy known
      to facilitate aneuploid malignancies. Here, we show that tetraploid cells
      produced by impaired chromosomal condensation are eliminated by a novel type of
      cell death different from caspase-dependent apoptosis. The cell death was
      associated with downregulation of eukaryotic translation elongation factor-1
      alpha 1 (eEF1A1/EF-1alpha) expression in conjunction with accumulation of its
      mRNA in processing bodies (P bodies). Importantly, expression of exogenous eEF1A1
      was shown to inhibit the caspase-independent cell death, and a similar cell death
      was observed after inducing the expression of short hairpin RNA specific for
      eEF1A1. Furthermore, the number of spontaneously arising binucleated cells was
      indicated to increase several fold during 1- to 2-week cultivation after
      initiation of exogenous eEF1A expression. Taken together, the novel cell death
      machinery should help to eliminate abnormal tetraploid cells and inhibit
      tumorigenesis.

PMID- 18820647
TI  - Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver
      disease.
AB  - Nonalcoholic fatty liver disease (NAFLD) is a burgeoning health problem of
      unknown etiology that varies in prevalence among ancestry groups. To identify
      genetic variants contributing to differences in hepatic fat content, we carried
      out a genome-wide association scan of nonsynonymous sequence variations (n =
      9,229) in a population comprising Hispanic, African American and European
      American individuals. An allele in PNPLA3 (rs738409[G], encoding I148M) was
      strongly associated with increased hepatic fat levels (P = 5.9 x 10(-10)) and
      with hepatic inflammation (P = 3.7 x 10(-4)). The allele was most common in
      Hispanics, the group most susceptible to NAFLD; hepatic fat content was more than
      twofold higher in PNPLA3 rs738409[G] homozygotes than in noncarriers.
      Resequencing revealed another allele of PNPLA3 (rs6006460[T], encoding S453I)
      that was associated with lower hepatic fat content in African Americans, the
      group at lowest risk of NAFLD. Thus, variation in PNPLA3 contributes to ancestry
      related and inter-individual differences in hepatic fat content and
      susceptibility to NAFLD.

PMID- 18820648
TI  - Long-term effects of large-volume liposuction on metabolic risk factors for
      coronary heart disease.
AB  - Abdominal obesity is associated with metabolic risk factors for coronary heart
      disease (CHD). Although we previously found that using liposuction surgery to
      remove abdominal subcutaneous adipose tissue (SAT) did not result in metabolic
      benefits, it is possible that postoperative inflammation masked the beneficial
      effects. Therefore, this study provides a long-term evaluation of a cohort of
      subjects from our original study. Body composition and metabolic risk factors for
      CHD, including oral glucose tolerance, insulin resistance, plasma lipid profile,
      and blood pressure were evaluated in seven obese (39 +/- 2 kg/m(2)) women before
      and at 10, 27, and 84-208 weeks after large-volume liposuction. Liposuction
      surgery removed 9.4 +/- 1.8 kg of body fat (16 +/- 2% of total fat mass; 6.1 +/-
      1.4 kg decrease in body weight), primarily from abdominal SAT; body composition
      and weight remained the same from 10 through 84-208 weeks. Metabolic endpoints
      (oral glucose tolerance, homeostasis model assessment of insulin resistance,
      blood pressure and plasma triglyceride (TG), high-density lipoprotein (HDL)
      cholesterol, and low-density lipoprotein (LDL)-cholesterol concentrations)
      obtained at 10 through 208 weeks were not different from baseline and did not
      change over time. These data demonstrate that removal of a large amount of
      abdominal SAT by using liposuction does not improve CHD metabolic risk factors
      associated with abdominal obesity, despite a long-term reduction in body fat.

PMID- 18820649
TI  - Circulating leptin and stress-induced cardiovascular activity in humans.
AB  - Obesity is associated with an elevated risk of hypertension and cardiovascular
      disease. The adipocyte hormone leptin, which stimulates energy expenditure in
      animals by activating the sympathetic nervous system (SNS), is believed to play a
      role in this association. However, evidence in humans remains sparse. We
      investigated the relationship between circulating leptin and cardiovascular and
      inflammatory responses to acute psychological stress in humans. Participants were
      32 men and 62 women aged 18-25 years. Cardiovascular activity was assessed using
      impedance cardiography at baseline, during acute laboratory stress, and during a
      45-min recovery period. Plasma cytokines were measured in blood drawn at baseline
      and 45-min poststress. In women only, baseline plasma leptin was significantly
      associated with stress-induced changes in heart rate (beta = 0.53, P = 0.006),
      heart rate variability (HRV) (beta = -0.44, P = 0.015), and cardiac preejection
      period (PEP) (beta = -0.51, P = 0.004), independent of age, adiposity, and
      smoking. Women's plasma leptin levels also correlated with stress-induced
      elevations in the proinflammatory cytokine interleukin-6 (IL-6) (beta = 0.35, P =
      0.042). Circulating leptin is an independent predictor of sympathetic
      cardiovascular activity, parasympathetic withdrawal, and inflammatory responses
      to stress in women. Because cardiovascular and inflammatory stress responses are
      predictive of future cardiovascular disease, leptin may be a mechanism mediating
      the adverse effects of stress and obesity on women's cardiovascular health.

PMID- 18820650
TI  - Central obesity as a precursor to the metabolic syndrome in the AusDiab study and
      Mauritius.
AB  - Evidence from epidemiologic studies that central obesity precedes future
      metabolic change and does not occur concurrently with the appearance of the blood
      pressure, glucose, and lipid abnormalities that characterize the metabolic
      syndrome (MetS) has been lacking. Longitudinal surveys were conducted in
      Mauritius in 1987, 1992, and 1998, and in Australia in 2000 and 2005 (AusDiab).
      This analysis included men and women (aged > or = 25 years) in three cohorts:
      AusDiab 2000-2005 (n = 5,039), Mauritius 1987-1992 (n = 2,849), and Mauritius
      1987-1998 (n = 1,999). MetS components included waist circumference, systolic
      blood pressure, fasting and 2-h postload plasma glucose, high-density lipoprotein
      (HDL) cholesterol, triglycerides, and homeostasis model assessment of insulin
      sensitivity (HOMA-S) (representing insulin sensitivity). Linear regression was
      used to determine which baseline components predicted deterioration in other MetS
      components over 5 years in AusDiab and 5 and 11 years in Mauritius, adjusted for
      age, sex, and ethnic group. Baseline waist circumference predicted deterioration
      (P < 0.01) in four of the other six MetS variables tested in AusDiab, five of six
      in Mauritius 1987-1992, and four of six in Mauritius 1987-1998. In contrast, an
      increase in waist circumference between baseline and follow-up was only predicted
      by insulin sensitivity (HOMA-S) at baseline, and only in one of the three
      cohorts. These results suggest that central obesity plays a central role in the
      development of the MetS and appears to precede the appearance of the other MetS
      components.

PMID- 18820651
TI  - Telomere length is associated with obesity parameters but with a gender
      difference.
AB  - Cardiovascular disease (CVD) and obesity have been coupled to short telomere
      length in peripheral blood. The biological background to this observation is not
      obvious from the literature. In this study we have analyzed a large set of known
      risk factors for CVD in relation to telomere length in blood cells on a merged
      cohort of 989 individuals recruited in the Malmo Diet and Cancer Cohort (MDCC)
      and the Northern Sweden MONICA project. We found a significant or borderline
      association between obesity parameters and telomere length in women after age and
      center adjustments (BMI: r = -0.106, P = 0.021, weight: r = -0.087, P = 0.060,
      waist circumference: r = -0.099, P = 0.032, hip circumference: r = -0.128, P =
      0.005). In men, a positive borderline correlation to high-density lipoprotein
      (HDL) (r = 0.111, P = 0.053) and a negative correlation to 2-h post-oral glucose
      tolerance test (OGTT) was observed (r = -0.202, P = 0.045). In neither group any
      association was found between telomere length and cholesterol, serum
      triglycerides, serum low-density lipoprotein, plasma insulin, blood pressure,
      pulse pressure, or smoking habits. Our data indicate that telomere length is
      associated with an "obesity-phenotype" but only in women.

PMID- 18820652
TI  - Metabolic predictors of inflammation, adhesion, and coagulability in healthy
      younger-aged adults.
AB  - Elevated levels of inflammatory biomarkers are associated with the
      pathophysiology of cardiovascular diseases and are predictors of cardiovascular
      events. The objective of this study was to determine the unique contributions of
      metabolic factors as predictors of inflammation (C-reactive protein (CRP) and
      interleukin-6 (IL-6)), adhesion (soluble intercellular adhesion molecule-1 (sICAM
      1)), and coagulation (D-dimer) in healthy younger-aged adults. Participants were
      83 women and 92 men (mean age 30.04 years, s.d. +/- 4.8, range 22-39) of normal
      weight to moderate obese weight (mean BMI 24.4 kg/m(2), s.d. +/- 3.35, range 17
      32). The primary data analytical approaches included Pearson correlation and
      multiple linear regression. Circulating levels of CRP, IL-6, sICAM-1, and D-dimer
      were determined in plasma. Higher levels of CRP were independently associated
      with higher BMI, a greater waist-to-hip ratio, female gender, and higher
      triglycerides (P < 0.001). Higher IL-6 levels were independently associated with
      a greater waist-to-hip ratio (P < 0.01). Higher levels of sICAM-1 were
      independently associated with higher BMI, higher triglycerides, and lower insulin
      resistance (P < 0.001). Higher D-dimer levels were independently associated with
      higher BMI and being female (P < 0.001). Having a higher BMI was most
      consistently associated with elevated biomarkers of inflammation, adhesion, and
      coagulation in this sample of healthy younger-aged adults, although female
      gender, insulin resistance, and lipid levels were also related to the biomarkers.
      The findings provide insight into the adverse cardiovascular risk associated with
      elevated body weight in younger adults.

PMID- 18820653
TI  - Adiponectin multimers and metabolic syndrome traits: relative adiponectin
      resistance in African Americans.
AB  - African Americans (AAs) tend to have lower total adiponectin levels compared to
      European Americans (EA); however, it is not known whether race affects
      adiponectin multimer distribution and their relationships to metabolic traits. We
      measured total adiponectin, high molecular weight (HMW), low molecular weight
      (LMW) (i.e., hexamer), and trimer adiponectin in 132 normoglycemic premenopausal
      women (75 AAs, 57 EAs), together with measures of total and abdominal fat, plasma
      lipids, insulin sensitivity (S(i)), and genetic admixture estimates. We found
      that lower total adiponectin in AAs was explained by reduced LMW, and trimer
      forms because levels of HMW did not differ between races. In EAs, HMW was highly
      correlated with multiple metabolic syndrome traits. In contrast, the LMW and
      trimer forms were most highly correlated with metabolic traits in AAs, including
      abdominal adiposity, lipids, and S(i). At similar levels of visceral adiposity,
      AAs exhibited significantly lower LMW adiponectin than EAs. Similarly, at
      comparable levels of HMW and LMW adiponectin, AAs were more insulin resistant
      than their EA counterparts. In conclusion, (i) serum adiponectin is lower in AAs
      predominantly as a result of reduced concentrations of LMW and trimers multimeric
      forms; (ii) LMW and trimer, not HMW, are most broadly correlated with metabolic
      traits in AAs. Thus, HMW adiponectin may exert less bioactivity in explaining the
      metabolic syndrome trait cluster in populations of predominant African genetic
      background.

PMID- 18820654
TI  - Breathing variability at rest is positively associated with 24-h blood pressure
      level.
AB  - BACKGROUND: Previous research has reported that inhibition of breathing can be
      observed in hypertensive patients at rest during the daytime, as well as in sleep
      at night. The present study hypothesized that the variability of breathing and
      end-tidal CO(2) (PetCO(2)) in seated women at rest is positively associated with
      their 24-h blood pressure level. METHODS: Breath-to-breath measures of breathing
      rate and tidal volume were recorded via inductive plethysmography in each of 54
      women during two 20-min sessions of seated rest, and in 32 women during night
      time sleep. PetCO(2) was also recorded during these sessions via a respiratory
      gas monitor. Ambulatory blood pressure was recorded for 24 h between the two
      clinic sessions via oscillometry. RESULTS: Breath pauses >10 s were observed
      significantly more often in women in the upper than the lower tertile of 24-h
      systolic blood pressure. Breath-to-breath variability in breathing rate, tidal
      volume, and minute ventilation were greater in the higher blood pressure tertile
      women. Variability in PetCO(2) was also greater in high blood pressure tertile.
      These associations were independent of age, weight, and body surface area (BSA).
      Breathing variability was inversely correlated with heart rate variability (HRV).
      CONCLUSION: Greater variability in breathing at rest that is independent of
      metabolic activity characterizes women with elevated blood pressure. The linear
      association of breathing variability with 24-h blood pressure level is consistent
      with the hypothesis that intermittent breathing inhibition may predispose to the
      development of some forms of hypertension.

PMID- 18820655
TI  - Von Willebrand factor as marker of vascular function in South African women: the
      POWIRS Study.
AB  - BACKGROUND: The increasing prevalence of hypertension and vascular-related
      morbidity and mortality among Africans emphasizes the need to identify markers
      for the early detection of vascular disease. Caucasian-based studies demonstrate
      that the von Willebrand factor (vWf) is a useful marker of vascular dysfunction.
      We investigated whether associations between this marker and markers of
      cardiovascular function in Caucasian women are comparable with African women.
      METHODS: The study consisted of apparently healthy African (n = 99) and Caucasian
      (n = 114) women (mean age, 31.0 years), individually matched for age and body
      mass index. We measured blood pressure and arterial compliance noninvasively, and
      vWf in serum. We assessed univariate and multivariate-adjusted associations of
      blood pressure and arterial compliance with vWf. RESULTS: Although no ethnic
      difference existed for mean vWf levels, Caucasian and African women showed
      opposite associations of blood pressure and arterial compliance with vWf after
      single, partial, and multiple regression analyses. In Caucasians, after full
      adjustment, systolic (beta = +0.179; P < 0.05) and diastolic (beta = +0.190; P <
      0.05) blood pressure correlated positively and arterial compliance negatively
      (beta = -0.197; P < 0.01) with vWf. Conversely, in Africans, systolic blood
      pressure correlated weakly, but negatively (beta = -0.168; P = 0.059) with vWf.
      However, this opposite tendency seemed due to the confounding influence of the
      depot medroxyprogesterone acetate (DMPA) contraceptive injection and, although
      >99% power existed, significance disappeared after excluding these subjects (beta
      = -0.071; P = 0.46). CONCLUSIONS: Associations of vWf with blood pressure and
      arterial compliance were not comparable between Caucasian and African women,
      suggesting that the vWf may not be a useful marker of vascular alterations in
      African women.

PMID- 18820656
TI  - Secondary pseudomonas infection of fungal keratitis following use of contaminated
      natamycin eye drops: a case series.
AB  - AIM: To report a five case of secondary pseudomonas infection of fungal keratitis
      following use of contaminated natamycin eye drops. METHODS: A retrospective
      analysis of the course and clinical outcomes of five eyes of five patients with
      clinical and laboratory-confirmed fungal keratitis species was performed.
      Clinical worsening despite hourly topical 5% natamycin drops prompted a repeat
      corneal scraping and microbiological evaluation. RESULTS: The causative fungi for
      the initial keratitis were Fusarium and Aspergillus species. All the five
      specimens obtained from repeat scrapings revealed Pseudomonas aeruginosa. The
      cultures obtained from the natamycin eye drops being used by the patients also
      grew pseudomonas. On further evaluation, the source of contamination of the
      natamycin containers was obscure but speculated to be nosocomial, being within
      the hospital or the pharmacy. All patients had a poor visual outcome with one
      requiring evisceration because of panophthalmitis, whereas three underwent
      therapeutic keratoplasty. CONCLUSIONS: A high index of suspicion is recommended
      in all cases of worsening fungal keratitis to identify secondary contamination of
      antifungal agents with nosocomial infections.

PMID- 18820657
TI  - Case-control study of subconjunctival triamcinolone acetonide injection vs
      intravenous methylprednisolone pulse in the treatment of endothelial corneal
      allograft rejection.
AB  - PURPOSE: To assess the safety and effectiveness of treating corneal endothelial
      rejection with a subconjunctival injection of 20 mg triamcinolone acetonide in
      combination with topical application of 1% prednisolone acetate, as compared to
      treatment with an intravenous pulse of 500 mg methylprednisolone in combination
      with topical application of 1% prednisolone acetate. METHODS: A case-controlled
      study including a literature review was performed. Patients who presented with an
      initial episode of corneal endothelial rejection were treated with
      subconjunctival injection of 20 mg triamcinolone in combination with topically
      applied 1% prednisolone and were retrospectively matched for age and diagnosis to
      patients who received a single intravenous injection of 500 mg methylprednisolone
      in combination with topical 1% prednisolone. Patients were analysed regarding
      reversion of the rejection episode, intraocular pressure, and visual acuity after
      1 year. RESULTS: Overall, the triamcinolone group had a better outcome regarding
      reversion of corneal transplant rejection (P=0.025), with 15 of 16 patients in
      the triamcinolone group having clear grafts, compared to only 10 of 16 patients
      in the methylprednisolone group. Intraocular pressure (IOP) was increased in both
      groups at day 30 (P=0.002), although there was no statistically significant
      difference in IOP between the groups (P=0.433). Visual acuity improved in both
      groups after 1 year (P=0.049), although slightly more improvement was observed in
      the triamcinolone group (P=0.002). CONCLUSIONS: The results observed in this case
      controlled study suggest that the use of subconjunctival triamcinolone acetonide
      may benefit patients with corneal transplant rejection.

PMID- 18820658
TI  - Dosage dependence of the effect of Ginkgo biloba on the rat retinal ganglion cell
      survival after optic nerve crush.
AB  - PURPOSE: To investigate the dosage dependence of the Ginkgo biloba effect on
      retinal ganglion cell survival in the rat optic nerve crush model. METHODS: The
      study included 56 Sprague-Dawley rats, the right optic nerve of which was crushed
      in a standardized manner. Two hours after the crush and once daily during the
      follow-up, the animals received intragastral applications of saline (saline
      group; n=13), or of a G. biloba extract of 0.25% concentration (n=14; low-dosage
      group), 1% concentration (n=15; medium-dosage group), or 4% concentration (n=14;
      high-dosage group). At 23 days after the optic nerve crush, the retinal ganglion
      cells were retrogradely labelled by injecting 3% fluorogold into the superior
      colliculi of the brain. At 4 weeks after baseline, the animals were killed.
      Retinal flat mount photographs were assessed for number and density of the
      retinal ganglion cells. RESULTS: The mean survival rate defined as the ratio of
      retinal ganglion cell density in the right eye with optic nerve crash divided by
      the retinal ganglion cell density in left eye without optic nerve intervention
      increased significantly (P<0.001) from 58.4+/-9.0% in the saline group to 68.5+/
      5.7% in the low-dosage group, to 73.7+/-6.4% in the medium-dosage group, and to
      74.2+/-6.8% in the high-dosage group. CONCLUSIONS: Intragastral applications of a
      G. biloba extract applied after an experimental and standardized optic nerve
      crush in rats were associated with a higher survival rate of retinal ganglion
      cells in a dosage-dependent manner.

PMID- 18820659
TI  - Nurse-led formal health review for immunosuppressed patients with uveitis.
AB  - PURPOSE: To describe and analyse a method of detailed formal health review for
      patients with sight-threatening uveitis using oral immunosuppression. METHODS:
      Prospective clinical study of 37 patients. RESULTS: Treatment side effects were
      absent or tolerable in 31 patients (84%) but 34 significant treatment side
      effects or other significant clinical findings were newly identified. Ten
      patients underwent a treatment change including three who transferred to a
      different immunosuppressive. CONCLUSIONS: Formal health review has proved useful
      in identifying treatment side effects previously not volunteered by patients. A
      modified form is to be embedded within our clinic management system. We recommend
      such reviews to enhance drug safety in patients with sight-threatening chronic
      uveitis using oral immunosuppressives.

PMID- 18820660
TI  - Superficial primitive Ewing's sarcoma: a clinicopathologic and molecular
      cytogenetic analysis of 14 cases.
AB  - Superficial primitive Ewing's sarcomas are rare and have been reported to be of
      favorable prognosis compared to conventional deep-seated tumors. In the skin and
      subcutis, the diagnosis is often difficult, and performing molecular cytogenetic
      techniques may be helpful. We performed a retrospective analysis of 14 cases of
      superficial Ewing's sarcomas, all confirmed by molecular cytogenetics. Clinical,
      histological, immunohistochemical, molecular cytogenetic, therapeutic, and follow
      up data are reported. There were 11 female and 3 male patients aged from 12 to 77
      years (median: 17 years). Seven tumors occurred in the extremities, five in the
      trunk wall, and two in the head. Tumor size ranged from 1 to 5 cm (median, 3 cm).
      They were all small round-cell proliferations with a strong membranous positivity
      for CD99. Ewing's sarcoma translocations/fusion gene transcripts were detected in
      eight cases, both by FISH and reverse transcriptase (RT)-PCR. Four tumors were
      positive by RT-PCR alone (FISH not done in three cases and not interpretable in
      one case), and two cases were positive by FISH alone (RT-PCR not done). Surgical
      resection was performed in all patients. Chemotherapy was given in ten patients
      and radiotherapy in six. At last medical examination (median follow-up, 47
      months), two patients who underwent surgical resection alone had died from the
      tumor. Our results confirm that superficial Ewing's sarcomas are of good
      prognosis. Given the difficulty of the diagnosis and the importance of an adapted
      treatment, a confirmation of the diagnosis by molecular or cytogenetic techniques
      is recommended when dealing with a superficial tumor.

PMID- 18820661
TI  - t(11;18)(q21;q21) in extranodal marginal zone B-cell lymphoma of mucosa
      associated lymphoid tissue in stomach: a study of 48 cases.
AB  - Gastric extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid
      tissue (MZL-MALT) is speculated to be immune mediated and is notable for
      responding to treatment by Helicobacter pylori eradication. However, the gastric
      MZL-MALT with t(11;18)(q21;q21) has been shown to be resistant to treatment by H.
      pylori eradication. We studied the molecular, immunohistochemical, and
      histological aspects of 48 cases of gastric MZL-MALT and used a reverse
      transcription real-time PCR assay to assess the presence of a t(11;18)(q21;q21)
      in formalin-fixed, paraffin-embedded tissue. Florescence in situ hybridization
      for t(11:18)(q21;q21) was used to confirm the real-time PCR results. Three
      distinct morphological subtypes were recognized: monocytoid, small lymphocytic,
      and plasmacytoid. Morphology, immunophenotype, and immunoglobulin heavy chain
      (IgH) gene rearrangement were correlated with the results of the
      t(11:18)(q21;q21) assay. Of the 48 analyzed cases, 15 (31%) were positive for
      t(11;18)(q21;q21) and 33 (69%) were monoclonal for IgH gene rearrangement. Of the
      15, 13 (87%) cases with t(11;18)(q21;q21) translocation showed IgH gene
      rearrangement by PCR. Of the 33 t(11;18)(q21;q21)-negative cases tested, 20 cases
      (61%) showed IgH gene rearrangement. The 15 t(11;18)(q21;q21) translocation
      positive cases had either monocytoid (12 of 15) or small lymphocytic morphology
      (3 of 15). Aberrant expression of CD43 was observed in 8 of 15 (53%)
      t(11;18)(q21;q21)-positive cases and 21 of 31 (68%) t(11;18)(q21;q21)-negative
      cases. Our data show that t(11;18)(q21;q21)-positive MZL-MALTs frequently show
      monocytoid morphology, less often small lymphocytic morphology, and not purely
      plasmacytoid morphology. Identification of a t(11;18)(q21;q21) by reverse
      transcription real-time PCR is highly specific for MZL-MALT and helps in the
      diagnosis of MZL-MALT. Studying the correlation between this translocation and
      morphological features may increase our understanding of the role of this
      translocation in the pathogenesis and the clinical behavior of gastric MZL-MALT.

PMID- 18820662
TI  - Primary cutaneous marginal zone B-cell lymphoma: a molecular and
      clinicopathological study of cases from Asia, Germany, and the United States.
AB  - Primary cutaneous marginal zone B-cell lymphoma is considered the cutaneous
      counterpart of extranodal marginal zone B-cell lymphoma of mucosa-associated
      lymphoid tissue. Although its molecular pathogenesis is currently unknown, an
      etiological link with Borrelia burgdorferi infection has been identified in
      European, but not in American or Asian cases. To better understand the
      pathogenesis and the geographical differences of cutaneous marginal zone B-cell
      lymphoma, 60 cases from the East Asia, Germany, and the United States at their
      initial presentation were subjected to the following analyses; (1)
      clinicopathological comparison between the geographical regions, (2) detection of
      B. burgdorferi DNA, (3) detection of the API2-MALT1 fusion transcript, a gene
      alteration specific to mucosa-associated lymphoid tissue lymphoma, and (4)
      inactivation of tumor suppressor genes (death-associated protein kinase (DAPK),
      p16(INK4a), p14(ARF), MGMT, TIMP3, CDH1, and RARB) by hypermethylation of the CpG
      islands. Cases from the three geographical regions showed similar
      clinicopathological features. However, moderate/marked tissue eosinophilia was
      found in 9/25 Asian cases, but only 1/23 German cases (P=0.011) and 0/12 American
      cases (P=0.015). All 60 cases were negative for either Borrelia DNA or API2-MALT1
      fusion. Tumors from the three regions were highly methylated for DAPK (38-50% of
      the cases, mean 43%) and p16(INK4a) (42-70%, mean 49%), and the positivities were
      significantly higher than those of nonneoplastic skin (8%, P=0.0010 and 14%,
      P=0.0032, respectively). Methylation of these genes had no significant
      association with progressive features of the tumor. Primary cutaneous marginal
      zone B-cell lymphomas from the three geographical regions have common
      clinicopathological features, however, moderate/marked tissue eosinophilia is a
      feature found almost exclusively in Asian cases. Borrelia infection and API2
      MALT1 fusion are not significant in this tumor. Methylation of DAPK and
      p16(INK4a) genes is a frequent event in this lymphoma at its initial
      presentation, but may not be associated with tumor progression.

PMID- 18820663
TI  - The number of lymph nodes identified in a simple pancreatoduodenectomy specimen:
      comparison of conventional vs orange-peeling approach in pathologic assessment.
AB  - Lymph node status is one of the most important predictors of survival in
      resectable pancreatic ductal adenocarcinoma; therefore, thorough lymph node
      evaluation is a critical assessment in pancreatoduodenectomy specimens. There is
      considerable variability in pancreatoduodenectomy specimens processed
      histologically. This study compares two approaches of lymph node dissection and
      evaluation (standard vs orange peeling) of pancreatoduodenectomy specimens. A
      different approach to dissection of pancreatoduodenectomy specimens was designed
      to optimize lymph node harvesting: All peripancreatic soft tissues were removed
      in an orange-peeling manner before further dissection of the pancreatic head.
      This approach was applied to 52 consecutive pancreatoduodenectomy specimens
      performed for ductal adenocarcinoma at two institutions. Specimen dissection was
      otherwise performed routinely. Overall number of lymph nodes harvested, number of
      positive lymph nodes, and their anatomic distribution were analyzed and compared
      with cases that had been dissected by the conventional approach. The mean number
      of lymph nodes identified by the orange-peeling approach was 14.1 (by
      institution, 13.8 and 14.4), as opposed to 6.1 (by institution, 7 and 5.3) in
      cases processed by conventional approach (P=0.0001). The number of lymph node
      positive cases also increased substantially from 50% (by institution, 54 and 46%)
      in the conventional method to 73% (by institution, 88 and 58%) in the orange
      peeling method (P=0.02). The orange-peeling method of lymph node harvest in
      pancreatoduodenectomy specimens for ductal adenocarcinoma enhances overall and
      positive lymph node yield and optimizes ductal adenocarcinoma staging. Therefore,
      lymph node harvest by the orange-peeling method should be performed routinely
      before specimen sectioning in assessment of pancreatoduodenectomy for ductal
      adenocarcinoma.

PMID- 18820664
TI  - Primary retroperitoneal myxoid/round cell liposarcoma is a nonexisting disease:
      an immunohistochemical and molecular biological analysis.
AB  - Almost all primary retroperitoneal liposarcomas can be classified as well
      /dedifferentiated liposarcoma. Rarely, however, primary retroperitoneal
      liposarcoma is classified as myxoid/round cell liposarcoma, based on the presence
      of myxoid areas and vascular crow's feet pattern, which has resulted in a debate
      on the classification of liposarcoma in the retroperitoneum. Genetically,
      myxoid/round cell liposarcoma and well-/dedifferentiated liposarcoma are
      different diseases. Myxoid/round cell liposarcoma is characterized by a
      translocation causing FUS-CHOP or EWSR1-CHOP fusion, whereas well
      /dedifferentiated liposarcoma is characterized by an amplification of the 12q13
      15 region, including MDM2 and CDK4 genes. As myxoid/round cell liposarcoma is
      highly radio- and chemosensitive, differentiation between subtypes is important
      to optimize treatment. We studied whether primary retroperitoneal liposarcomas
      diagnosed as myxoid/round cell liposarcoma represent molecularly true
      myxoid/round cell liposarcoma or are histopathological mimics and represent well
      /dedifferentiated liposarcoma. Primary retroperitoneal myxoid/round cell
      liposarcoma (n=16) were compared to primary extremity myxoid/round cell
      liposarcoma (n=20). Histopathological and immunohistochemical features were
      studied. Amplification status of the 12q13-15 region was studied using a
      multiplex ligation-dependent probe amplification analysis, and FUS-CHOP or EWS
      CHOP translocations were studied using RT-PCR. In primary retroperitoneal
      myxoid/round cell liposarcoma, MDM2 and CDK4 staining was both positive in 12 of
      15 cases. In primary extremity myxoid/round cell liposarcoma, MDM2 was negative
      in 18/20 and CDK4 was negative in all cases. Multiplex ligation-dependent probe
      amplification showed the amplification of 12q13-15 region in 16/16 primary
      retroperitoneal myxoid/round cell liposarcomas and in 1/20 primary extremity
      myxoid/round cell liposarcomas. Translocation was present in all (18/18) primary
      extremity myxoid/round cell liposarcomas, but absent in all primary
      retroperitoneal myxoid/round cell liposarcomas. On the basis of
      immunohistochemical and molecular characteristics, apparent primary
      retroperitoneal myxoid/round cell liposarcoma can be recognized as well
      /dedifferentiated liposarcoma with morphological features mimicking myxoid/round
      cell liposarcoma. In these cases, treatment should probably be specifically
      designed as for well-/dedifferentiated liposarcoma. Moreover, finding of
      myxoid/round cell liposarcoma translocations in a retroperitoneal localization is
      highly suggestive of metastasis and should prompt search for a primary
      localization outside the retroperitoneum.

PMID- 18820665
TI  - Brachyury, SOX-9, and podoplanin, new markers in the skull base chordoma vs
      chondrosarcoma differential: a tissue microarray-based comparative analysis.
AB  - The distinction between chondrosarcoma and chordoma of the skull base/head and
      neck is prognostically important; however, both have sufficient morphologic
      overlap to make delineation difficult. As a result of gene expression studies,
      additional candidate markers have been proposed to help in separating those
      entities. We sought to evaluate the performance of new markers: brachyury, SOX-9,
      and podoplanin alongside the more traditional markers glial fibrillary acid
      protein, carcinoembryonic antigen, CD24, and epithelial membrane antigen.
      Paraffin blocks from 103 skull base/head and neck chondroid tumors from 70
      patients were retrieved (1969-2007). Diagnoses were made based on morphology
      and/or whole-section immunohistochemistry for cytokeratin and S100 protein
      yielding 79 chordomas (comprising 45 chondroid chordomas and 34 conventional
      chordomas), and 24 chondrosarcomas. A tissue microarray containing 0.6 mm cores
      of each tumor in triplicate was constructed using a manual array (MTA-1; Beecher
      Instruments). For visualization of staining, the ImmPRESS detection system
      (Vector Laboratories) with 2-diaminobenzidine substrate was used. Sensitivities
      and specificities were calculated for each marker. Core loss from the microarray
      ranged from 25 to 29% yielding 66-78 viable cases per stain. The classic marker,
      cytokeratin, still has the best performance characteristics. When combined with
      brachyury, accuracy improves slightly (sensitivity and specificity for detection
      of chordoma 98 and 100%, respectively). Positivity for both epithelial membrane
      antigen and AE1/AE3 had a sensitivity of 90% and a specificity of 100% for
      detecting chordoma in this study. SOX-9 is apparently common to both notochordal
      and cartilaginous differentiation, and is not useful in the chordoma
      chondrosarcoma differential diagnosis. Glial fibrillary acid protein,
      carcinoembryonic antigen, CD24, and epithelial membrane antigen did not
      outperform other markers, and are less useful in the diagnosis of chordoma vs
      chondrosarcoma. Podoplanin still remains the only positive marker for
      chondrosarcoma, though its accuracy is less than previously reported.

PMID- 18820666
TI  - Immunosuppressive regulatory T cells are associated with aggressive breast cancer
      phenotypes: a potential therapeutic target.
AB  - FoxP3 is a marker for immunosuppressive CD25+CD4+ regulatory T cells. These
      regulatory T cells are thought to play a role in inducing immune tolerance to
      antigens and may be selectively recruited by carcinomas. We investigated whether
      breast carcinomas had significant numbers of FoxP3-positive regulatory T cells by
      immunohistochemistry, and if their presence was associated with other prognostic
      factors, such as Nottingham grade, hormone receptor immunohistochemical profile,
      tumor size, or lymph node metastases. Ninety-seven needle core or excisional
      breast biopsies with invasive breast carcinoma diagnosed at the University of
      Washington were stained with antibodies to FoxP3, estrogen receptor, and
      Her2/neu. The numbers of FoxP3-positive cells present within the neoplastic
      epithelium, and immediately adjacent stroma were counted manually in three high
      powered fields (HPFs; x 400) by two independent pathologists. The average scores
      were then correlated with the parameters of interest. A threshold of >or=15 FoxP3
      positive cells/HPF was used to define a FoxP3-positive case in some analyses.
      Higher average numbers of FoxP3-positive cells present significantly correlated
      with higher Nottingham grade status (P=0.000229). In addition, the presence of
      significant numbers (>or=15/HPF) of FoxP3-positive cells in breast carcinoma was
      positively associated with higher Nottingham grade (P=0.00002585). Higher average
      numbers of FoxP3-positive cells were also significantly associated with larger
      tumor size (>2.0 cm; P=0.012824) and trended toward an association with estrogen
      receptor negativity. Interestingly, 'triple-negative' (estrogen and progesterone
      receptor negative and Her2/neu negative) Nottingham grade III cases were also
      significantly associated with high numbers of FoxP3 cells. These results argue
      that regulatory T cells may play a role in inducing immune tolerance to higher
      grade, more aggressive breast carcinomas, and are a potential therapeutic target
      for these cancers.

PMID- 18820667
TI  - D2-40 in breast cancer: should we detect more vascular emboli?
AB  - Peritumoral emboli assessed on hematoxylin-eosin-stained slides are taken into
      account for treatment of patients with operable breast cancer. We assessed
      whether immunostaining with D2-40 improves the prognostic significance of emboli
      in a group of tumors with a large immunohistochemical sampling and a long-term
      follow-up. Topography, number, and extension of hematoxylin-eosin and D2-40
      emboli were compared in 94 node-negative breast cancers (median number of
      immunostained slides per tumor: 3). Metastasis-free survival of patients with or
      without hematoxylin-eosin and/or D2-40 emboli were evaluated (median follow-up of
      178 months). Hematoxylin-eosin emboli were detected in 14 (15%) tumors and were
      located at distance from the tumor. D2-40 emboli were detected in 39 (41%) tumors
      and was often multiple (n=30), extensive (n=23), located within (n=13), close to
      (n=10) or at distance from the tumor (n=16). The 12 distant hematoxylin-eosin and
      D2-40 emboli were located in the same vessels (seven missed at the first
      hematoxylin-eosin examination and secondarily diagnosed by D2-40 staining). A
      difference in metastasis-free survival was found only between patients with no D2
      40 emboli and those with distant D2-40 emboli (P=0.02). D2-40 emboli located
      within or close to the tumor had no prognostic value. Comparing the metastasis
      free survival of patients with or without hematoxylin-eosin emboli, the
      prognostically unfavorable significance of hematoxylin-eosin emboli was improved
      when taking into account the seven patients with missed emboli at the first
      examination and secondarily diagnosed by D2-40 staining (P=0.006 vs 0.003). To
      conclude, D2-40 increases the diagnostic sensitivity of emboli in breast
      carcinoma and the high incidence of D2-40 emboli might be related to the number
      of immunostained slides per case. Nevertheless, only distant D2-40+ emboli had a
      prognostic impact. In practice, D2-40 might be useful to detect missed
      hematoxylin-eosin emboli especially in cases without any other prognostically
      unfavorable criterion.

PMID- 18820668
TI  - Intrarenal ectopic adrenal tissue and renal-adrenal fusion: a report of nine
      cases.
AB  - Intrarenal ectopic adrenal tissue and renal-adrenal fusion are rare findings in
      the adult population. We reviewed seven cases of intrarenal adrenal tissue and
      two cases of renal-adrenal fusion. Patients ranged in age from 35 to 75 years
      (mean 55). Ectopic adrenal tissue was identified at the superior pole of the
      kidney in all but one case, which was located in the mid-portion of the kidney.
      Ectopic adrenal tissue varied in its growth from subcapsular lesions that were
      plaque-like (n=3), wedge-shaped (n=2), or spherical (n=1) to irregular nests deep
      in the renal parenchyma (n=1). In all nine cases, the adherent and intrarenal
      adrenal tissue was composed of adrenal cortical tissue, with no adrenal medullary
      tissue present. In six cases, adrenal tissue focally extended into renal
      parenchyma in an infiltrative manner. Of the nine cases, two were diagnostic
      problems for the contributing pathologists. In one case, intrarenal adrenal
      tissue mimicked low-grade clear cell renal cell carcinoma. In another case, an
      adrenocortical adenoma adherent to the kidney resembled renal invasion by
      adrenocortical carcinoma. This study summarizes key morphological features of
      intrarenal ectopic adrenal tissue and renal-adrenal fusion along with
      histological pitfalls and its differential diagnoses.

PMID- 18820669
TI  - DNA copy number alterations correlate with survival of esophageal adenocarcinoma
      patients.
AB  - Despite recent advances in surgical and multidisciplinary treatment, prognosis
      for patients with esophageal adenocarcinoma remains poor, and the low prognostic
      significance of pTNM staging suggests that additional parameters are needed. To
      identify genomic abnormalities characteristic of esophageal adenocarcinoma, a
      panel of 33 samples obtained at surgery from previously untreated patients were
      analyzed by muliplex ligation-dependent probe amplification technique. We
      detected frequent gains of 6p, 8q, 13q, 17q, 20q, and losses of 4q, 5q, 15q, and
      18q. When DNA copy number changes were correlated to clinicopathological features
      of patients no association was found between the number of chromosomal
      aberrations and gender, age, tumor grade or pTNM staging. However, interestingly,
      a significant correlation between patient survival and total number of
      chromosomal aberrations was found when esophageal adenocarcinoma cases were
      stratified according to the median of survival (20 months) (P=0.002) or the
      median of aberrations (12 aberrations) (P=0.014). Evaluation of the distribution
      of gains and losses at the level of single chromosomes indicated that gains on
      chromosomes 5, 6, 8, 11, 20 and losses on chromosomes 1, 3, 5, 11, and 18 were
      significantly different in the two survival groups. Furthermore, when single gene
      imbalances were analyzed in further details, we found that besides alterations
      that involve genes shared by both survival groups, a few genes (KIAA0170, EMS1,
      ABCC4, F3, and MIF) were altered only in samples from patients with poor
      survival. Thus, we established a good correlation between the total number of
      chromosomal alterations and survival, suggesting that the estimation of total
      imbalances might represent an additional indicator of disease outcome. In
      addition, the finding of alterations specific for the more aggressive esophageal
      adenocarcinoma subset might represent promising biomarkers to increase the
      accuracy of clinical outcome prediction.

PMID- 18820670
TI  - Multiple genes are hypermethylated in intraductal papillary mucinous neoplasms of
      the pancreas.
AB  - Ductal adenocarcinoma of the pancreas is the fourth leading cause of cancer death
      and is usually diagnosed late. Intraductal papillary mucinous neoplasms are an
      increasingly recognized precursor to invasive ductal adenocarcinoma of the
      pancreas. Identifying the alterations in DNA methylation that arise during
      intraductal papillary mucinous neoplasm development may facilitate the
      development of markers that could be used to differentiate intraductal papillary
      mucinous neoplasms from non-neoplastic pancreatic cystic lesions. Surgically
      resected intraductal papillary mucinous neoplasms and adjacent ductal
      adenocarcinomas were microdissected from 50 patients. Normal pancreas was also
      obtained from 27 patients with intraductal papillary mucinous neoplasms or
      pancreatic adenocarcinomas and 10 patients with well-differentiated pancreatic
      endocrine neoplasms. Methylation-specific PCR was performed on isolated DNA for
      seven genes (SPARC, SARP2, TSLC1, RELN, TFPI2, CLDN5, UCHL1) known to be commonly
      aberrantly methylated in pancreatic ductal adenocarcinomas. The mean percentage
      of genes methylated in invasive ductal adenocarcinomas arising in association
      with an intraductal papillary mucinous neoplasm (mean+/-s.d., 81+/-17%) was
      significantly higher than that in noninvasive-intraductal papillary mucinous
      neoplasms (57+/-26%, P=0.007) or peritumoral normal epithelial cells (22+/-17%,
      P<0.0001). Carcinomas (intraductal papillary mucinous neoplasms with carcinoma in
      situ or their associated infiltrating adenocarcinoma) had significantly more
      methylated genes (71+/-19%) than low-grade (low and moderate dysplasia)
      intraductal papillary mucinous neoplasms (44+/-26%, P<0.0001). The mean
      percentage of genes methylated in histologically normal pancreatic ductal cells
      from patients with ductal neoplasia (22+/-17%) was significantly higher than in
      normal ductal cells from patients with well-differentiated pancreatic endocrine
      neoplasms (4+/-7%, P=0.002). Thus, aberrant DNA methylation increases with
      histologic grades of intraductal papillary mucinous neoplasm. Low-level aberrant
      methylation in the normal ductal cells is more prevalent in patients with ductal
      neoplasia than in controls without ductal neoplasms and may contribute to
      carcinogenesis. The detection of aberrant methylation in pancreatic cystic
      lesions could facilitate the diagnosis of intraductal papillary mucinous
      neoplasms.

PMID- 18820671
TI  - Clinical significance of the distribution of C4d deposits in different anatomic
      compartments of the allograft kidney.
AB  - Diffuse C4d deposition in peritubular capillaries is a well-recognized marker of
      antibody-mediated rejection. The significance of staining patterns that are focal
      or affect non-peritubular capillary compartments is less well defined. Paired
      frozen section and paraffin-embedded tissue stains were performed in 52 kidney
      allograft biopsies, and correlated with clinicopathologic parameters. Diffuse
      peritubular capillary C4d deposits were more often seen in frozen sections
      (22/52, 43% frozen tissue vs 10/52, 19% paraffin-embedded tissue), whereas focal
      staining was observed more frequently within paraffin sections (13/52, 25%
      paraffin-embedded tissue vs 7/52, 14% frozen tissue). In biopsies taken from
      patients with a history of donor-specific antibodies, diffuse, focal and negative
      peritubular capillary C4d staining patterns were seen in 11/14 (79%), 1/14 (7%)
      and 2/14 (14%) of frozen biopsies vs 5/14 (36%), 6/14 (43%) and 3/14 (21%) of
      paraffin-embedded biopsies. Transplant glomerulopathy score in paraffin-embedded
      biopsies was higher in specimens with vs without glomerular basement membrane C4d
      staining (1.5+/-0.8 vs 1.0+/-0.6, P=0.03). Tubular basement membrane staining was
      present in 4% paraffin-embedded and 48% frozen specimens independent of tubular
      atrophy. Arteriolar hyalinosis score in paraffin-embedded specimens was higher in
      biopsies with vs those without arteriolar C4d deposits (1.3+/-0.9 vs 0.9+/-0.8,
      P=0.04). Arterial staining was unrelated to the degree of intimal thickening. In
      conclusion, peritubular capillary deposits correlate well with circulating donor
      specific antibody. For paraffin-embedded tissue, combining the results of focal
      and diffuse staining allows a diagnostic sensitivity comparable to diffuse
      staining in frozen tissue. Finally, C4d deposits preferentially in lesions of
      chronic transplant glomerulopathy and arteriolar hyalinosis.

PMID- 18820672
TI  - Characterization of a novel anti-fatty acid synthase (FASN) antiserum in breast
      tissue.
AB  - Fatty acid synthase (FASN) expression has been reported in many different tumors,
      including breast cancer. In gene microarray studies, the fatty acid synthase gene
      co-clustered with cytokeratins 5 and 17 and other genes that defined the basal
      like subset of breast cancers. To define the use of this marker in breast
      pathology, a rabbit polyclonal antiserum (S143) to a peptide fragment of this
      gene was produced and compared with a commercially available monoclonal antibody
      by immunohistochemistry on various tissue microarrays and whole tissue sections.
      The tissue microarrays included 1090 breast cancers and 244 normal breast
      tissues. Whole tissue sections consisted of benign and malignant tissues from
      breast resection specimens. In contrast to other 'basal' markers identified by
      gene expression profiling data, the fatty acid synthase (FASN) expression pattern
      in normal breast was notable for its expression in only a small subset of basal
      and suprabasal cells. Dual staining experiments revealed that the subpopulation
      of cells labeling with FASN did not coexpress myoepithelial markers CK5/6 or p63,
      but did coexpress e-cadherin. In addition to staining a subset of basal and
      suprabasal cells, the antiserum highlighted apocrine differentiation, and stained
      106/144 (74%) cases of columnar cell lesions and five of five cases of flat
      epithelial atypia. Despite its association with basal keratins in gene array
      studies, FASN expression did not correlate significantly with the outcome in
      breast cancer. We describe an expression pattern that highlights only a subset of
      basal and suprabasal cells in normal breast ducts and we show by dual expression
      studies that this subset of cells is different from myoepithelial and basal
      cytokeratin-positive cells. In addition, FASN expression is described in apocrine
      metaplasia, columnar cell lesions, and flat epithelial atypia.

PMID- 18820673
TI  - Loss of 13q is associated with genes involved in cell cycle and proliferation in
      dedifferentiated hepatocellular carcinoma.
AB  - Dedifferentiation of hepatocellular carcinoma implies aggressive clinical
      behavior and is associated with an increasing number of genomic alterations, eg
      deletion of 13q. Genes directly or indirectly deregulated due to these genomic
      alterations are mainly unknown. Therefore this study compares array comparative
      genomic hybridization and whole genome gene expression data of 23 well,
      moderately, or poorly dedifferentiated hepatocellular carcinoma, using
      unsupervised hierarchical clustering. Dedifferentiated carcinoma clearly branched
      off from well and moderately differentiated carcinoma (P<0.001 chi(2)-test).
      Within the dedifferentiated group, 827 genes were upregulated and 33 genes were
      downregulated. Significance analysis of microarrays for hepatocellular carcinoma
      with and without deletion of 13q did not display deregulation of any gene located
      in the deleted region. However, 531 significantly upregulated genes were
      identified in these cases. A total of 6 genes (BIC, CPNE1, RBPMS, RFC4, RPSA,
      TOP2A) were among the 20 most significantly upregulated genes both in
      dedifferentiated carcinoma and in carcinoma with loss of 13q. These genes are
      involved in cell-cycle control and proliferation. Of 33 downregulated genes in
      the dedifferentiated subgroup, 4 metallothioneins had the lowest fold change,
      most probably mediated through inactivation of C/EBPalpha by the PI3K/AKT
      cascade. In conclusion dedifferentiation of hepatocellular carcinoma is
      associated with upregulation of genes involved in cell-cycle control and
      proliferation. Notably, a significant portion of these genes is also upregulated
      in carcinoma with deletion of 13q. As no downregulated genes were identified and
      microRNAs (mir-621, mir-16-1, mir-15a) are located within the deleted region of
      13q and may be lost, we speculate that these miRNAs may induce the upregulation
      of critical cell-cycle control genes.

PMID- 18820674
TI  - Epithelioid trophoblastic tumor: comparative genomic hybridization and diagnostic
      DNA genotyping.
AB  - Arising from the putative chorionic-type intermediate trophoblast, epithelioid
      trophoblastic tumor is a recent addition to the spectrum of gestational
      trophoblastic diseases. Frequently, the tumor involves the uterine cervix and is
      misdiagnosed as invasive squamous-cell carcinoma. The pathogenesis of the tumor
      is poorly understood, and its molecular analysis is essentially lacking. This
      study was designed to explore chromosomal alterations in epithelioid
      trophoblastic tumor and to use DNA genotyping to demonstrate its trophoblastic
      origin, therefore separating the tumor from its mimics of the maternal origin.
      Five cases of epithelioid trophoblastic tumors were included in this study and
      paired DNA samples from the tumor and normal tissue were extracted from paraffin
      embedded archival materials. The status of chromosomal alterations was analyzed
      by comparative genomic hybridization using conventional metaphase chromosome
      preparations. The parental genetic contribution was determined by DNA genotyping
      analysis using AmpFISTR Identifiler Amplification system (Applied Biosystems
      Inc.). Comparative genomic hybridization analysis was successful in three cases
      analyzed, all of which showed a balanced chromosomal profile without detectable
      gain or loss of the genome. DNA genotyping was informative in four epithelioid
      trophoblastic tumor involving anatomic locations including the cervix (two
      cases), endomyometrium (one case) and lung (metastatic, one case). All four cases
      were found to have unique paternal alleles, confirming the trophoblastic nature
      of the tumors. In summary, chromosomal alterations detectable by conventional
      comparative genomic hybridization are not features of epithelioid trophoblastic
      tumors. In difficult cases, the presence of the paternal alleles demonstrated by
      DNA genotyping is a powerful diagnostic application in separating an epithelioid
      trophoblastic tumor from its maternal mimics, particularly the far more common
      squamous-cell carcinoma of the uterine cervix.

PMID- 18820675
TI  - TCL1A expression delineates biological and clinical variability in B-cell
      lymphoma.
AB  - The assembly of a collection of gene-expression signatures of the major types of
      B-cell non-Hodgkin's lymphoma has identified increased T-cell leukemia/lymphoma
      1A (TCL1) expression in multiple lymphoma types and cases, and has enabled the
      investigation of the functional and clinical importance of TCL1 expression.
      Specifically, Burkitt's lymphoma cases show a homogeneously strong expression of
      TCL1, whereas diffuse large B-cell lymphoma, follicular lymphoma, mantle cell
      lymphoma, chronic lymphocytic leukemia, nodal marginal zone lymphoma, and splenic
      marginal zone lymphoma display a striking variability in the intensity of TCL1
      staining. This was validated in two independent series. A Gene-Set Enrichment
      Analysis of the genes correlated with TCL1A expression found that variation in
      the level of expression of TCL1A was significantly associated with some of the
      most important gene signatures recognizing B-cell lymphoma pathogenesis and
      heterogeneity, such as germinal center, B-cell receptor, NF-kappaB (and its
      target genes), death, MAP kinases, TNFR1, TOLL, and IL1R. Additionally, TCL1
      expression was correlated with shorter time to treatment in chronic lymphocytic
      leukemia cases and shorter lymphoma-specific survival in mantle cell lymphoma
      series, thus indicating the clinical and biological significance of TCL1
      expression, and suggesting TCL1A as a potential therapeutic target.

PMID- 18820676
TI  - Digestive histopathological presentation of IPEX syndrome.
AB  - Immunodysregulation, polyendocrinopathy, enteropathy, and X-linked inheritance
      (IPEX) syndrome is a well recognized and particularly severe form of autoimmune
      enteropathy. It has an X-linked recessive transmission, and is caused by
      mutations in the FOXP3 gene. We studied the intestinal morphological changes
      characterizing IPEX syndrome in a series of 12 children with a molecularly
      confirmed diagnosis. Histological examination of duodenal, gastric and colonic
      biopsies were retrospectively reviewed and compared by two independent
      experienced pathologists. In parallel, the presence of circulating anti
      enterocyte antibodies was analysed using an indirect immunofluorescence technique
      and a quantitative radioligand assay against the 75-kDa autoantigen. The
      morphology of the inflammatory gut lesions could be categorized into three
      different entities, namely graft-vs-host disease-like changes (9/12 patients), a
      coeliac disease-like pattern (2/12) and an enteropathy with a complete depletion
      of goblet cells (1/12). Our results do not suggest any phenotype-genotype
      correlation. Circulating antibodies were detected in all 12 patients, with an
      anti-brush border pattern (11/12) and anti-goblet cell antibodies (1/12), as well
      as by a radioligand assay. The histological presentation of autoimmune
      enteropathy is rather variable. However, a graft-vs-host disease-like pattern
      associated with positive anti-enterocyte antibodies is the most frequent
      intestinal presentation of IPEX syndrome, and constitutes a very valuable tool
      for pathologists to suspect this diagnosis.

PMID- 18820677
TI  - The CRAC channel consists of a tetramer formed by Stim-induced dimerization of
      Orai dimers.
AB  - Ca(2+)-release-activated Ca(2+) (CRAC) channels underlie sustained Ca(2+)
      signalling in lymphocytes and numerous other cells after Ca(2+) liberation from
      the endoplasmic reticulum (ER). RNA interference screening approaches identified
      two proteins, Stim and Orai, that together form the molecular basis for CRAC
      channel activity. Stim senses depletion of the ER Ca(2+) store and physically
      relays this information by translocating from the ER to junctions adjacent to the
      plasma membrane, and Orai embodies the pore of the plasma membrane calcium
      channel. A close interaction between Stim and Orai, identified by co
      immunoprecipitation and by Forster resonance energy transfer, is involved in the
      opening of the Ca(2+) channel formed by Orai subunits. Most ion channels are
      multimers of pore-forming subunits surrounding a central channel, which are
      preassembled in the ER and transported in their final stoichiometry to the plasma
      membrane. Here we show, by biochemical analysis after cross-linking in cell
      lysates and intact cells and by using non-denaturing gel electrophoresis without
      cross-linking, that Orai is predominantly a dimer in the plasma membrane under
      resting conditions. Moreover, single-molecule imaging of green fluorescent
      protein (GFP)-tagged Orai expressed in Xenopus oocytes showed predominantly two
      step photobleaching, again consistent with a dimeric basal state. In contrast, co
      expression of GFP-tagged Orai with the carboxy terminus of Stim as a cytosolic
      protein to activate the Orai channel without inducing Ca(2+) store depletion or
      clustering of Orai into punctae yielded mostly four-step photobleaching,
      consistent with a tetrameric stoichiometry of the active Orai channel.
      Interaction with the C terminus of Stim thus induces Orai dimers to dimerize,
      forming tetramers that constitute the Ca(2+)-selective pore. This represents a
      new mechanism in which assembly and activation of the functional ion channel are
      mediated by the same triggering molecule.

PMID- 18820678
TI  - Stepwise chromatin remodelling by a cascade of transcription initiation of non
      coding RNAs.
AB  - Recent transcriptome analyses using high-density tiling arrays and data from
      large-scale analyses of full-length complementary DNA libraries by the FANTOM3
      consortium demonstrate that many transcripts are non-coding RNAs (ncRNAs). These
      transcriptome analyses indicate that many of the non-coding regions, previously
      thought to be functionally inert, are actually transcriptionally active regions
      with various features. Furthermore, most relatively large ( approximately several
      kilobases) polyadenylated messenger RNA transcripts are transcribed from regions
      harbouring little coding potential. However, the function of such ncRNAs is
      mostly unknown and has been a matter of debate. Here we show that RNA polymerase
      II (RNAPII) transcription of ncRNAs is required for chromatin remodelling at the
      fission yeast Schizosaccharomyces pombe fbp1(+) locus during transcriptional
      activation. The chromatin at fbp1(+) is progressively converted to an open
      configuration, as several species of ncRNAs are transcribed through fbp1(+). This
      is coupled with the translocation of RNAPII through the region upstream of the
      eventual fbp1(+) transcriptional start site. Insertion of a transcription
      terminator into this upstream region abolishes both the cascade of transcription
      of ncRNAs and the progressive chromatin alteration. Our results demonstrate that
      transcription through the promoter region is required to make DNA sequences
      accessible to transcriptional activators and to RNAPII.

PMID- 18820679
TI  - The ectodomain of Toll-like receptor 9 is cleaved to generate a functional
      receptor.
AB  - Mammalian Toll-like receptors (TLRs) 3, 7, 8 and 9 initiate immune responses to
      infection by recognizing microbial nucleic acids; however, these responses come
      at the cost of potential autoimmunity owing to inappropriate recognition of self
      nucleic acids. The localization of TLR9 and TLR7 to intracellular compartments
      seems to have a role in facilitating responses to viral nucleic acids while
      maintaining tolerance to self nucleic acids, yet the cell biology regulating the
      transport and localization of these receptors remains poorly understood. Here we
      define the route by which TLR9 and TLR7 exit the endoplasmic reticulum and travel
      to endolysosomes in mouse macrophages and dendritic cells. The ectodomains of
      TLR9 and TLR7 are cleaved in the endolysosome, such that no full-length protein
      is detectable in the compartment where ligand is recognized. Notably, although
      both the full-length and cleaved forms of TLR9 are capable of binding ligand,
      only the processed form recruits MyD88 on activation, indicating that this
      truncated receptor, rather than the full-length form, is functional. Furthermore,
      conditions that prevent receptor proteolysis, including forced TLR9 surface
      localization, render the receptor non-functional. We propose that ectodomain
      cleavage represents a strategy to restrict receptor activation to endolysosomal
      compartments and prevent TLRs from responding to self nucleic acids.

PMID- 18820680
TI  - Comprehensive mass-spectrometry-based proteome quantification of haploid versus
      diploid yeast.
AB  - Mass spectrometry is a powerful technology for the analysis of large numbers of
      endogenous proteins. However, the analytical challenges associated with
      comprehensive identification and relative quantification of cellular proteomes
      have so far appeared to be insurmountable. Here, using advances in computational
      proteomics, instrument performance and sample preparation strategies, we compare
      protein levels of essentially all endogenous proteins in haploid yeast cells to
      their diploid counterparts. Our analysis spans more than four orders of magnitude
      in protein abundance with no discrimination against membrane or low level
      regulatory proteins. Stable-isotope labelling by amino acids in cell culture
      (SILAC) quantification was very accurate across the proteome, as demonstrated by
      one-to-one ratios of most yeast proteins. Key members of the pheromone pathway
      were specific to haploid yeast but others were unaltered, suggesting an efficient
      control mechanism of the mating response. Several retrotransposon-associated
      proteins were specific to haploid yeast. Gene ontology analysis pinpointed a
      significant change for cell wall components in agreement with geometrical
      considerations: diploid cells have twice the volume but not twice the surface
      area of haploid cells. Transcriptome levels agreed poorly with proteome changes
      overall. However, after filtering out low confidence microarray measurements,
      messenger RNA changes and SILAC ratios correlated very well for pheromone pathway
      components. Systems-wide, precise quantification directly at the protein level
      opens up new perspectives in post-genomics and systems biology.

PMID- 18820681
TI  - Triggering the succinate receptor GPR91 on dendritic cells enhances immunity.
AB  - Succinate acts as an extracellular mediator signaling through the G protein
      coupled receptor GPR91. Here we show that dendritic cells had high expression of
      GPR91. In these cells, succinate triggered intracellular calcium mobilization,
      induced migratory responses and acted in synergy with Toll-like receptor ligands
      for the production of proinflammatory cytokines. Succinate also enhanced antigen
      specific activation of human and mouse helper T cells. GPR91-deficient mice had
      less migration of Langerhans cells to draining lymph nodes and impaired tetanus
      toxoid-specific recall T cell responses. Furthermore, GPR91-deficient allografts
      elicited weaker transplant rejection than did the corresponding grafts from wild
      type mice. Our results suggest that the succinate receptor GPR91 is involved in
      sensing immunological danger, which establishes a link between immunity and a
      metabolite of cellular respiration.

PMID- 18820682
TI  - Priming for T helper type 2 differentiation by interleukin 2-mediated induction
      of interleukin 4 receptor alpha-chain expression.
AB  - T helper type 2 (T(H)2) cells are essential for humoral immunity and host
      defense. Interleukin 4 (IL-4) drives T(H)2 differentiation and IL-2 augments the
      accessibility of Il4 chromatin. Here we demonstrate that IL-2, by inducing
      binding of STAT5 to the Il4ra locus, which encodes IL-4 receptor alpha-chain (IL
      4Ralpha), was essential for inducing and maintaining IL-4Ralpha expression.
      Although IL-4 induced IL-4Ralpha expression, T cell receptor-induced IL-4Ralpha
      expression was normal in Il4(-/-) cells but was much lower in Il2(-/-) cells.
      Notably, forced IL-4Ralpha expression restored the T(H)2 differentiation of Il2(
      /-) cells. Moreover, genome-wide mapping by chromatin immunoprecipitation coupled
      with sequencing showed broad interaction of the transcription factors STAT5A and
      STAT5B with genes associated with T(H)2 differentiation. Our results identify a
      previously unappreciated function for IL-2 in 'priming' T cells for T(H)2
      differentiation and in maintaining the expression of Il4ra and other genes in
      T(H)2-committed cells.

PMID- 18820683
TI  - Modulation of the antitumor immune response by complement.
AB  - The involvement of complement-activation products in promoting tumor growth has
      not yet been recognized. Here we show that the generation of complement C5a in a
      tumor microenvironment enhanced tumor growth by suppressing the antitumor CD8(+)
      T cell-mediated response. This suppression was associated with the recruitment of
      myeloid-derived suppressor cells into tumors and augmentation of their T cell
      directed suppressive abilities. Amplification of the suppressive capacity of
      myeloid-derived suppressor cells by C5a occurred through regulation of the
      production of reactive oxygen and nitrogen species. Pharmacological blockade of
      the C5a receptor considerably impaired tumor growth to a degree similar to the
      effect produced by the anticancer drug paclitaxel. Thus, our study demonstrates a
      therapeutic function for complement inhibition in the treatment of cancer.

PMID- 18820684
TI  - Systems-level metabolic flux profiling identifies fatty acid synthesis as a
      target for antiviral therapy.
AB  - Viruses rely on the metabolic network of their cellular hosts to provide energy
      and building blocks for viral replication. We developed a flux measurement
      approach based on liquid chromatography-tandem mass spectrometry to quantify
      changes in metabolic activity induced by human cytomegalovirus (HCMV). This
      approach reliably elucidated fluxes in cultured mammalian cells by monitoring
      metabolome labeling kinetics after feeding cells (13)C-labeled forms of glucose
      and glutamine. Infection with HCMV markedly upregulated flux through much of the
      central carbon metabolism, including glycolysis. Particularly notable increases
      occurred in flux through the tricarboxylic acid cycle and its efflux to the fatty
      acid biosynthesis pathway. Pharmacological inhibition of fatty acid biosynthesis
      suppressed the replication of both HCMV and influenza A, another enveloped virus.
      These results show that fatty acid synthesis is essential for the replication of
      two divergent enveloped viruses and that systems-level metabolic flux profiling
      can identify metabolic targets for antiviral therapy.

PMID- 18820685
TI  - Genome sequencing and analysis of the filamentous fungus Penicillium chrysogenum.
AB  - Industrial penicillin production with the filamentous fungus Penicillium
      chrysogenum is based on an unprecedented effort in microbial strain improvement.
      To gain more insight into penicillin synthesis, we sequenced the 32.19 Mb genome
      of P. chrysogenum Wisconsin54-1255 and identified numerous genes responsible for
      key steps in penicillin production. DNA microarrays were used to compare the
      transcriptomes of the sequenced strain and a penicillinG high-producing strain,
      grown in the presence and absence of the side-chain precursor phenylacetic acid.
      Transcription of genes involved in biosynthesis of valine, cysteine and alpha
      aminoadipic acid-precursors for penicillin biosynthesis-as well as of genes
      encoding microbody proteins, was increased in the high-producing strain. Some
      gene products were shown to be directly controlling beta-lactam output. Many key
      cellular transport processes involving penicillins and intermediates remain to be
      characterized at the molecular level. Genes predicted to encode transporters were
      strongly overrepresented among the genes transcriptionally upregulated under
      conditions that stimulate penicillinG production, illustrating potential for
      future genomics-driven metabolic engineering.

PMID- 18820686
TI  - Notch signaling respecifies the hemangioblast to a cardiac fate.
AB  - To efficiently generate cardiomyocytes from embryonic stem (ES) cells in culture
      it is essential to identify key regulators of the cardiac lineage and to develop
      methods to control them. Using a tet-inducible mouse ES cell line to enforce
      expression of a constitutively activated form of the Notch 4 receptor, we show
      that signaling through the Notch pathway can efficiently respecify hemangioblasts
      to a cardiac fate, resulting in the generation of populations consisting of >60%
      cardiomyocytes. Microarray analyses reveal that this respecification is mediated
      in part through the coordinated regulation of the BMP and Wnt pathways by Notch
      signaling. Together, these findings have uncovered a potential role for the Notch
      pathway in cardiac development and provide an approach for generating large
      numbers of cardiac progenitors from ES cells.

PMID- 18820687
TI  - Hypermutation by intersegmental transfer of APOBEC3G cytidine deaminase.
AB  - Deamination of cytidine residues in single-stranded DNA (ssDNA) is an important
      mechanism by which apolipoprotein B mRNA-editing, catalytic polypeptide-like
      (APOBEC) enzymes restrict endogenous and exogenous viruses. The dynamic process
      underlying APOBEC-induced hypermutation is not fully understood. Here we show
      that enzymatically active APOBEC3G can be detected in wild-type Vif(+) HIV-1
      virions, albeit at low levels. In vitro studies showed that single enzyme-DNA
      encounters result in distributive deamination of adjacent cytidines. Nonlinear
      translocation of APOBEC3G, however, directed scattered deamination of numerous
      targets along the DNA. Increased ssDNA concentrations abolished enzyme
      processivity in the case of short, but not long, DNA substrates, emphasizing the
      key role of rapid intersegmental transfer in targeting the deaminase. Our data
      support a model by which APOBEC3G intersegmental transfer via monomeric binding
      to two ssDNA segments results in dispersed hypermutation of viral genomes.

PMID- 18820688
TI  - Plasticity of the PAS domain and a potential role for signal transduction in the
      histidine kinase DcuS.
AB  - The mechanistic understanding of how membrane-embedded sensor kinases recognize
      signals and regulate kinase activity is currently limited. Here we report
      structure-function relationships of the multidomain membrane sensor kinase DcuS
      using solid-state NMR, structural modeling and mutagenesis. Experimental data of
      an individual cytoplasmic Per-Arnt-Sim (PAS) domain were compared to structural
      models generated in silico. These studies, together with previous NMR work on the
      periplasmic PAS domain, enabled structural investigations of a membrane-embedded
      40-kDa construct by solid-state NMR, comprising both PAS segments and the
      membrane domain. Structural alterations are largely limited to protein regions
      close to the transmembrane segment. Data from isolated and multidomain constructs
      favor a disordered N-terminal helix in the cytoplasmic domain. Mutations of
      residues in this region strongly influence function, suggesting that protein
      flexibility is related to signal transduction toward the kinase domain and
      regulation of kinase activity.

PMID- 18820689
TI  - The S100A8-serum amyloid A3-TLR4 paracrine cascade establishes a pre-metastatic
      phase.
AB  - A large number of macrophages and haematopoietic progenitor cells accumulate in
      pre-metastatic lungs in which chemoattractants, such as S100A8 and S100A9, are
      produced by distant primary tumours serving as metastatic soil. The exact
      mechanism by which these chemoattractants elicit cell accumulation is not known.
      Here, we show that serum amyloid A (SAA) 3, which is induced in pre-metastatic
      lungs by S100A8 and S100A9, has a role in the accumulation of myeloid cells and
      acts as a positive-feedback regulator for chemoattractant secretion. We also show
      that in lung endothelial cells and macrophages, Toll-like receptor (TLR) 4 acts
      as a functional receptor for SAA3 in the pre-metastatic phase. In our study, SAA3
      stimulated NF-kappaB signalling in a TLR4-dependent manner and facilitated
      metastasis. This inflammation-like state accelerated the migration of primary
      tumour cells to lung tissues, but this was suppressed by the inhibition of either
      TLR4 or SAA3. Thus, blocking SAA3-TLR4 function in the pre-metastatic phase could
      prove to be an effective strategy for the prevention of pulmonary metastasis.

PMID- 18820690
TI  - Specialized neuronal adaptation for preserving input sensitivity.
AB  - Some neurons in auditory cortex respond to recent stimulus history by adapting
      their response functions to track stimulus statistics directly, as might be
      expected. In contrast, some neurons respond to loud sounds by adjusting their
      response functions away from high intensities and consequently remain sensitive
      to softer sounds. In marmoset monkey auditory cortex, the latter type of
      adaptation appears to exist only in neurons tuned to stimulus intensity.

PMID- 18820691
TI  - Forebrain steroid levels fluctuate rapidly during social interactions.
AB  - Neurosteroids are powerful modulators of brain function and behavior, yet their
      dynamics in the brain have remained elusive. Using in vivo microdialysis in male
      zebra finches, we found that local estradiol levels increased rapidly in the
      forebrain during social interactions with females. Furthermore, when males were
      exposed to other males' songs, local estradiol levels also increased and
      testosterone levels dropped in a cortical/pallial auditory region that is
      analogous to mammalian auditory cortex. We also found that local estradiol and
      testosterone levels were differentially regulated in this same region by the
      conventional neurotransmitters glutamate and GABA, respectively. This study
      provides direct evidence that forebrain steroid levels are acutely and
      differentially regulated during social behavior in a region-specific manner and
      in a rapid time course similar to that of traditional neuromodulators.

PMID- 18820692
TI  - Origin of correlated activity between parasol retinal ganglion cells.
AB  - Cells throughout the CNS have synchronous activity patterns; that is, a cell's
      probability of generating an action potential depends both on its firing rate and
      on the occurrence of action potentials in surrounding cells. The mechanisms
      producing synchronous or correlated activity are poorly understood despite its
      prevalence and potential effect on neural coding. We found that neighboring
      parasol ganglion cells in primate retina received strongly correlated synaptic
      input in the absence of modulated light stimuli. This correlated variability
      appeared to arise through the same circuits that provide uncorrelated synaptic
      input. In addition, ON, but not OFF, parasol cells were coupled electrically.
      Correlated variability in synaptic input, however, dominated correlations in the
      parasol spike outputs and shared variability in the timing of action potentials
      generated by neighboring cells. These results provide a mechanistic picture of
      how correlated activity is produced in a population of neurons that are critical
      for visual perception.

PMID- 18820694
TI  - Mirror-image representation of action in the anterior parietal cortex.
AB  - Mimicking hand actions made by someone facing us (that is, allocentric viewpoint)
      is typically performed with the opposite hand. Using functional magnetic
      resonance imaging (fMRI), we found a similar mirror-image representation of
      others' actions in the human anterior parietal cortex. Viewing egocentric-based
      actions elicited greater fMRI activation in the contralteral hemisphere (as in,
      self action), whereas observation of action seen from an allocentric viewpoint
      generated greater activation in the ipsilateral hemisphere. This mirror-like
      mapping occurs without active imitation, providing further evidence for an
      automatic action-simulation system in the parietal cortex.

PMID- 18820693
TI  - Beta-catenin is required for memory consolidation.
AB  - beta-catenin has been implicated in neuronal synapse regulation and remodeling.
      Here we have examined beta-catenin expression in the adult mouse brain and its
      role in amygdala-dependent learning and memory. We found alterations in beta
      catenin mRNA and protein phosphorylation during fear-memory consolidation. Such
      alterations correlated with a change in the association of beta-catenin with
      cadherin. Pharmacologically, this consolidation was enhanced by lithium-mediated
      facilitation of beta-catenin. Genetically, the role of beta-catenin was confirmed
      with site-specific deletions of loxP-flanked Ctnnb1 (encoding beta-catenin) in
      the amygdala. Baseline locomotion, anxiety-related behaviors and acquisition or
      expression of conditioned fear were normal. However, amygdala-specific deletion
      of Ctnnb1 prevented the normal transfer of newly formed fear learning into long
      term memory. Thus, beta-catenin may be required in the amygdala for the normal
      consolidation, but not acquisition, of fear memory. This suggests a general role
      for beta-catenin in the synaptic remodeling and stabilization underlying long
      term memory in adults.

PMID- 18820695
TI  - Questioning the role of rebound firing in the cerebellum.
AB  - A key component of recent theories on cerebellar function is rebound firing in
      neurons of the deep cerebellar nuclei (DCN). Despite the robustness of this
      phenomenon in vitro, in vivo studies have provided little evidence for its
      prevalence. We found that intact mouse or rat DCN neurons rarely showed rebound
      firing under physiological conditions in vitro or in vivo. These observations
      necessitate a critical re-evaluation of recent cerebellar models.

PMID- 18820696
TI  - Genetic control of rice plant architecture under domestication.
AB  - The closely related wild rice species Oryza rufipogon is considered the
      progenitor of cultivated rice (Oryza sativa). The transition from the
      characteristic plant architecture of wild rice to that of cultivated rice was one
      of the most important events in rice domestication; however, the molecular basis
      of this key domestication transition has not been elucidated. Here we show that
      the PROG1 gene controls aspects of wild-rice plant architecture, including tiller
      angle and number of tillers. The gene encodes a newly identified zinc-finger
      nuclear transcription factor with transcriptional activity and is mapped on
      chromosome 7. PROG1 is predominantly expressed in the axillary meristems, the
      site of tiller bud formation. Rice transformation experiments demonstrate that
      artificial selection of an amino acid substitution in the PROG1 protein during
      domestication led to the transition from the plant architecture of wild rice to
      that of domesticated rice.

PMID- 18820697
TI  - Variant between CPT1B and CHKB associated with susceptibility to narcolepsy.
AB  - Narcolepsy (hypocretin deficiency), a sleep disorder characterized by sleepiness,
      cataplexy and rapid eye movement (REM) sleep abnormalities, is tightly associated
      with HLA-DRB1*1501 (M17378) and HLA-DQB1*0602 (M20432). Susceptibility genes
      other than those in the HLA region are also likely involved. We conducted a
      genome-wide association study using 500K SNP microarrays in 222 Japanese
      individuals with narcolepsy and 389 Japanese controls, with replication of top
      hits in 159 Japanese individuals with narcolepsy and 190 Japanese controls,
      followed by the testing of 424 Koreans, 785 individuals of European descent and
      184 African Americans. rs5770917, a SNP located between CPT1B and CHKB, was
      associated with narcolepsy in Japanese (rs5770917[C], odds ratio (OR) = 1.79,
      combined P = 4.4 x 10(-7)) and other ancestry groups (OR = 1.40, P = 0.02). Real
      time quantitative PCR assays in white blood cells indicated decreased CPT1B and
      CHKB expression in subjects with the C allele, suggesting that a genetic variant
      regulating CPT1B or CHKB expression is associated with narcolepsy. Either of
      these genes is a plausible candidate, as CPT1B regulates beta-oxidation, a
      pathway involved in regulating theta frequency during REM sleep, and CHKB is an
      enzyme involved in the metabolism of choline, a precursor of the REM- and wake
      regulating neurotransmitter acetylcholine.

PMID- 18820698
TI  - Control of rice grain-filling and yield by a gene with a potential signature of
      domestication.
AB  - Grain-filling, an important trait that contributes greatly to grain weight, is
      regulated by quantitative trait loci and is associated with crop domestication
      syndrome. However, the genes and underlying molecular mechanisms controlling crop
      grain-filling remain elusive. Here we report the isolation and functional
      analysis of the rice GIF1 (GRAIN INCOMPLETE FILLING 1) gene that encodes a cell
      wall invertase required for carbon partitioning during early grain-filling. The
      cultivated GIF1 gene shows a restricted expression pattern during grain-filling
      compared to the wild rice allele, probably a result of accumulated mutations in
      the gene's regulatory sequence through domestication. Fine mapping with
      introgression lines revealed that the wild rice GIF1 is responsible for grain
      weight reduction. Ectopic expression of the cultivated GIF1 gene with the 35S or
      rice Waxy promoter resulted in smaller grains, whereas overexpression of GIF1
      driven by its native promoter increased grain production. These findings,
      together with the domestication signature that we identified by comparing
      nucleotide diversity of the GIF1 loci between cultivated and wild rice, strongly
      suggest that GIF1 is a potential domestication gene and that such a domestication
      selected gene can be used for further crop improvement.

PMID- 18820699
TI  - Control of a key transition from prostrate to erect growth in rice domestication.
AB  - The transition from the prostrate growth of ancestral wild rice (O. rufipogon
      Griff.) to the erect growth of Oryza sativa cultivars was one of the most
      critical events in rice domestication. This evolutionary step importantly
      improved plant architecture and increased grain yield. Here we find that
      prostrate growth of wild rice from Yuanjiang County in China is controlled by a
      semi-dominant gene, PROG1 (PROSTRATE GROWTH 1), on chromosome 7 that encodes a
      single Cys(2)-His(2) zinc-finger protein. prog1 variants identified in O. sativa
      disrupt the prog1 function and inactivate prog1 expression, leading to erect
      growth, greater grain number and higher grain yield in cultivated rice. Sequence
      comparison shows that 182 varieties of cultivated rice, including 87 indica and
      95 japonica cultivars from 17 countries, carry identical mutations in the prog1
      coding region that may have become fixed during rice domestication.

PMID- 18820700
TI  - Hydrothermal vents and the origin of life.
AB  - Submarine hydrothermal vents are geochemically reactive habitats that harbour
      rich microbial communities. There are striking parallels between the chemistry of
      the H(2)-CO(2) redox couple that is present in hydrothermal systems and the core
      energy metabolic reactions of some modern prokaryotic autotrophs. The
      biochemistry of these autotrophs might, in turn, harbour clues about the kinds of
      reactions that initiated the chemistry of life. Hydrothermal vents thus unite
      microbiology and geology to breathe new life into research into one of biology's
      most important questions - what is the origin of life?

PMID- 18820701
TI  - The cardiovascular threat of lupus.

PMID- 18820702
TI  - Wnt-beta-catenin signaling in the pathogenesis of osteoarthritis.
AB  - Osteoarthritis (OA) is a progressively degenerative joint condition that is
      influenced by various metabolic and structural factors. The canonical Wnt
      frizzled-beta-catenin pathway has been implicated in the pathogenesis of OA.
      Products of the Wnt, frizzled, secreted frizzled-related protein (sFRP), Dickkopf
      and LDL-receptor-related protein gene families have crucial roles in the
      development and maintenance of bone, cartilage and joints. Increased levels of
      beta-catenin have been observed in degenerative cartilage, suggesting that a
      diminished capacity to limit Wnt signaling might contribute to cartilage loss.
      Polymorphisms in genes involved in Wnt signaling-particularly in the gene
      encoding sFRP-3-are associated with an increased susceptibility to the
      development of OA. At least one of these polymorphisms in the gene encoding sFPR
      3 is associated with a reduced ability to limit beta-catenin signaling. In
      addition, the canonical Wnt signaling pathway is influenced by local factors,
      including alterations in glycosaminoglycan sulfation, cartilage matrix content,
      transforming growth factor beta and vitamin D. A higher circulating level of the
      Wnt inhibitor Dickkopf-1, for instance, is associated with slowed progression of
      hip OA. Hence, the sum of local and systemic factors contributes to the outcome
      of the Wnt-frizzled pathways. Further investigation is needed to fully define the
      role of Wnt signaling in OA.

PMID- 18820703
TI  - Polo-like kinase 1 phosphorylates and regulates Bcl-x(L) during pironetin-induced
      apoptosis.
AB  - Bcl-x(L), an anti-apoptotic Bcl-2 family member protein, contributes to the
      resistance against chemotherapies such as tubulin-binder treatment in many human
      tumors. Although Bcl-x(L) is phosphorylated after tubulin-binder treatment, the
      role of the phosphorylation and its responsible kinase(s) are poorly understood.
      Here, we identified Plk1 (polo-like kinase 1) as a Bcl-x(L) kinase. Same location
      of Bcl-x(L) and Plk1 was revealed by immunocytochemical analyses at M-phase in
      situ. Plk1 phosphorylates Bcl-x(L) in vitro, and we identified Plk1
      phosphorylation sites in Bcl-x(L). When all of these phosphorylation sites were
      substituted to alanines, the anti-apoptotic activity of the Bcl-x(L) mutant
      against the apoptosis induced by pironetin, but not against ultraviolet-induced
      apoptosis, was increased. These observations suggest that Plk1 is a regulator of
      Bcl-x(L) phosphorylation and controls the anti-apoptotic activity of Bcl-x(L)
      during pironetin-induced apoptosis.

PMID- 18820704
TI  - Combined inhibition of FLIP and XIAP induces Bax-independent apoptosis in type II
      colorectal cancer cells.
AB  - Death receptors can directly (type I cells) or indirectly induce apoptosis by
      activating mitochondrial-regulated apoptosis (type II cells). The level of
      caspase 8 activation is thought to determine whether a cell is type I or II, with
      type II cells less efficient at activating this caspase following death receptor
      activation. FLICE-inhibitory protein (FLIP) blocks death receptor-mediated
      apoptosis by inhibiting caspase 8 activation; therefore, we assessed whether
      silencing FLIP could convert type II cells into type I. FLIP silencing-induced
      caspase 8 activation in Bax wild-type and null HCT116 colorectal cancer cells;
      however, complete caspase 3 processing and apoptosis were only observed in Bax
      wild-type cells. Bax-null cells were also more resistant to chemotherapy and
      tumor necrosis factor-related apoptosis inducing ligand and, unlike the Bax wild
      type cells, were not sensitized to these agents by FLIP silencing. Further
      analyses indicated that release of second mitochondrial activator of caspases
      from mitochondria and subsequent inhibition of X-linked inhibitor of apoptosis
      protein (XIAP) was required to induce full caspase 3 processing and apoptosis
      following FLIP silencing. These results indicate that silencing FLIP does not
      necessarily bypass the requirement for mitochondrial involvement in type II
      cells. Furthermore, targeting FLIP and XIAP may represent a therapeutic strategy
      for the treatment of colorectal tumors with defects in mitochondrial-regulated
      apoptosis.

PMID- 18820705
TI  - Human and primate tumour viruses use PDZ binding as an evolutionarily conserved
      mechanism of targeting cell polarity regulators.
AB  - A unique feature of the cancer-causing mucosotropic human papillomaviruses (HPVs)
      is the ability of their E6 proteins to interact with a number of PDZ domain
      containing cellular substrates, including the cell polarity regulators hDlg and
      hScrib. These interactions are essential for the ability of these viruses to
      induce malignant progression. Rhesus papillomaviruses (RhPV) are similar to their
      human counterparts in that they also cause anogenital malignancy in their host,
      the Rhesus Macaque. However, unlike HPV E6, the RhPV E6 has no PDZ-binding motif.
      We now show that such a motif is present on the RhPV E7 oncoprotein. This motif
      specifically confers PDZ-binding activity and directs the interaction of RhPV E7
      with the cell polarity regulator Par3, which it targets for proteasome-mediated
      degradation. These results demonstrate an amazing evolutionary conservation of
      function between the RhPV and the HPV oncoproteins, where both target proteins of
      the same cell polarity control network, although through different components and
      pathways.

PMID- 18820706
TI  - Generation of an indestructible cyclin B1 by caspase-6-dependent cleavage during
      mitotic catastrophe.
AB  - Overriding the G(2) DNA damage checkpoint permits precocious entry into mitosis
      that ultimately leads to mitotic catastrophe. Mitotic catastrophe is manifested
      by an unscheduled activation of CDK1, caspase activation and apoptotic cell
      death. We found that although cyclin B1 was required for mitotic catastrophe, it
      was cleaved into a approximately 35 kDa protein by a caspase-dependent mechanism
      during the process. Cyclin B1 cleavage occurred after Asp123 in the motif
      ILVD(123) downward arrow, and mutation of this motif attenuated the cleavage.
      Cleavage was abolished by a pan-caspase inhibitor as well as by specific
      inhibitors for the effector caspase-6 and the initiator caspase-8. Cleavage
      created a truncated cyclin B1 lacking part of the NH(2)-terminal regulatory
      domain that included the destruction box sequence. Although cleavage of cyclin B1
      itself was not absolutely required for mitotic catastrophe, expression of the
      truncated product enhanced cell death. In support of this, ectopic expression of
      this truncated cyclin B1 was not only sufficient to induce mitotic block and
      apoptosis but also enhanced mitotic catastrophe induced by ionizing radiation and
      caffeine. These data underscore a possible linkage between mitotic and apoptotic
      functions by caspase-dependent processing of mitotic activators.

PMID- 18820707
TI  - Ubiquitin C-terminal hydrolase-L1 is a key regulator of tumor cell invasion and
      metastasis.
AB  - Ubiquitin C-terminal hydrolase-L1 (UCH-L1) catalyses the hydrolysis of ubiquitin
      ester and amide mainly in neuronal cells. Recently it was proposed as a marker
      with a potential role in carcinogenesis. However, the molecular mechanism
      underlying the biological function of UCH-L1 in tumor cells is poorly understood.
      We found that UCH-L1 is highly expressed in non-small lung cancer cell line H157,
      having high invasive potential, and that the expression of UCH-L1 in tumor cells
      enhances their invasive potential in vitro and in vivo. UCH-L1 changes cell
      morphology by regulating cell adhesion through Akt-mediated pathway. Suppressing
      UCH-L1 expression by RNAi significantly suppressed the invasion in vitro and in
      vivo, and the activation of Akt and downstream mitogen activated protein kinases
      c-Jun N-terminal kinases and p38, but not ERK. In Akt-negative mutants,
      overexpression of UCH-L1 does not affect the invasion and migration capability of
      H157 cells. These results suggest that UCH-L1 is a key molecule to regulate tumor
      cell invasion by upstream activation of Akt.

PMID- 18820708
TI  - p53 controls hPar1 function and expression.
AB  - Human protease-activated receptor 1 (hPar1) is a bona fide receptor of the
      hemostatic protease thrombin, and has a central function in tumor progression.
      Inactivation of the tumor suppressor gene p53 is one of the most common genomic
      alterations occurring in cancer. Here, we address the interrelations between p53
      and hPar1 in cancer. We demonstrate an inverse correlation between hPar1 gene
      expression and wild-type (wt) p53 levels, and a direct correlation with levels of
      the mutant (mt) p53. Bioinformatic search revealed the presence of at least two
      p53 motifs in the hPar1 promoter. Indeed, temperature-sensitive (ts) p53 forms
      reduced hPar1 promoter activity on wt p53 expression. Ectopic introduction of the
      p53R175H mutant into cells lacking p53 caused a moderate two-fold induction of
      hPar1 promoter activity. Chromatin immunoprecipitation (ChIP) analyses confirmed
      a physical association between the p53 protein and hPar1 chromatin fragments. In
      parallel, PAR1 function is attenuated by p53, as shown by inhibition of pFAK
      levels and a Matrigel invasion assay. Ectopic reinforcement of hPar1 rescued the
      inhibition conferred by p53, confirming that p53 directly affects hPar1
      expression and function. Altogether, we provide evidence for a direct binding
      between p53 and hPar1 chromatin, and assign hPar1 as a target of p53.

PMID- 18820709
TI  - Treatment of refractory acute GVHD with third-party MSC expanded in platelet
      lysate-containing medium.
AB  - Mesenchymal stem cells have been shown to mediate immunomodulatory effects. They
      have been used in patients with steroid-refractory acute GVHD (aGVHD), but their
      relevance as a therapeutic agent targeting aGVHD has still to be defined. In this
      case series, we report 13 patients with steroid-refractory aGVHD who received BM
      derived MSC expanded in platelet lysate-containing medium from unrelated HLA
      disparate donors. MSC were characterized by their morphological, phenotypical and
      functional properties. All tested preparations suppressed the proliferation of in
      vitro activated CD4+ T cells. MSC were transfused at a median dosage of 0.9 x
      10(6)/kg (range 0.6-1.1). The median number of MSC applications was 2 (range 1
      5). Only two patients (15%) responded and did not require any further escalation
      of immunosuppressive therapy. Eleven patients received additional salvage
      immunosuppressive therapy concomitant to further MSC transfusions, and after 28
      days, five of them (45%) showed a response. Four patients (31%) are alive after a
      median follow-up of 257 days, including one patient who initially responded to
      MSC treatment. In our patient cohort, response to MSC transfusion was lower than
      in the series reported earlier. However, our experience supports the potential
      efficacy of MSC in the treatment of steroid-refractory aGVHD.

PMID- 18820710
TI  - Contaminating tumour cells in autologous PBSC grafts do not influence survival or
      relapse following transplant for multiple myeloma or B-cell non-Hodgkin's
      lymphoma.
AB  - Relapsed disease remains a major obstacle following autologous haematopoietic SCT
      (HSCT) for non-Hodgkin's lymphoma (NHL) and multiple myeloma (MM). Studies
      regarding the importance of detectable tumour cells in PBSC collections have been
      inconclusive. Patients undergoing autologous HSCT for NHL and MM between 2001 and
      2006 were enrolled (n=158). PBSC grafts were assessed for clonal IgH CDR3 gene
      rearrangements using qualitative semi-nested PCR. In comparison to patients with
      PCR-positive PBSC grafts, patients negative for detectable disease had no
      improvement in overall survival (OS) or PFS for MM (P=0.91 and 0.91) or NHL
      (P=0.82 and 0.85). Further, no significant difference in OS was observed between
      patients with PCR-positive compared with PCR-negative PBSC grafts with aggressive
      NHL histology (P=0.74) or indolent disease (P=0.29). Patients with contaminating
      tumour cells in autologous PBSCs do not have worsened OS or PFS in MM or NHL.
      Tumour cells detected by sensitive molecular methods in PBSC collections may be
      distinct from cells contaminating marrow and appear to have limited utility in
      identifying patients with MM and B-cell NHL who would benefit from purging
      strategies.

PMID- 18820711
TI  - G-CSF-induced thrombocytopenia in a healthy donor.

PMID- 18820712
TI  - GVHD after chemotherapy conditioning in allogeneic transplanted mice.
AB  - GVHD is a major complication in allogeneic SCT. Available GVHD models are mainly
      based on radiotherapy-conditioning and/or immune deficient mice. GVHD models
      based on chemotherapy-based regimens remain poorly studied, despite 50% of all
      transplantations being chemotherapy based. Our aim was to develop a GVHD model
      using chemotherapy as conditioning. Female BALB/c (H-2Kd) were conditioned with
      BU-CY and transplanted with 2 x 10(7) BM and 3 x 10(7) spleen cells from either
      C57BL/6 (H-2 Kb) mice (allogeneic setting) or from male BALB/c to serve as a
      control group for regimen-related toxicity and engraftment. GVHD manifestations
      and histopathological changes were evaluated. Chimerism and donor T cells
      presence in skin, intestine and liver were studied using FACS-, FISH analysis and
      immunohistochemistry. Allogeneic transplanted mice developed lethal GVHD starting
      from day+7 with both histological and clinical signs. Donor T cells accumulated
      in recipient skin and intestine with GVHD progression. BM-failure, apoptosis and
      T-lymphocyte infiltration into target organs were significantly higher in
      allogeneic when compared with the syngeneic group. No toxicity or GVHD signs were
      observed in the syngeneic setting. We report a mouse model of GVHD using BU-CY
      conditioning that represents the most common myeloablative-conditioning regimen
      in clinical SCT. This model can be utilized to study the role of conditioning on
      mechanisms underlying GVHD.

PMID- 18820713
TI  - Central muscarinic receptor subtypes involved in pilocarpine-induced salivation,
      hypertension and water intake.
AB  - BACKGROUND AND PURPOSE: Recent evidence has suggested that pilocarpine (ACh
      receptor agonist) injected peripherally may act centrally producing salivation
      and hypertension. In this study, we investigated the effects of specific M(1)
      (pirenzepine), M(2)/M(4) (methoctramine), M(1)/M(3) (4-DAMP) and M(4)
      (tropicamide) muscarinic receptor subtype antagonists injected into the lateral
      cerebral ventricle (LV) on salivation, water intake and pressor responses to
      peripheral pilocarpine. EXPERIMENTAL APPROACH: Male Holtzman rats with stainless
      steel cannulae implanted in the LV were used. Salivation was measured in rats
      anaesthetized with ketamine (100 mg per kg body weight) and arterial pressure was
      recorded in unanaesthetized rats. KEY RESULTS: Salivation induced by i.p.
      pilocarpine (4 micromol per kg body weight) was reduced only by 4-DAMP (25-250
      nmol) injected into the LV, not by pirenzepine, methoctramine or tropicamide at
      the dose of 500 nmol. Pirenzepine (0.1 and 1 nmol) and 4-DAMP (5 and 10 nmol)
      injected into the LV reduced i.p. pilocarpine-induced water intake, whereas
      metoctramine (50 nmol) produced nonspecific effects on ingestive behaviours.
      Injection of pirenzepine (100 nmol) or 4-DAMP (25 and 50 nmol) into the LV
      reduced i.v. pilocarpine-induced pressor responses. Tropicamide (500 nmol)
      injected into the LV had no effect on pilocarpine-induced salivation, pressor
      responses or water intake. CONCLUSIONS AND IMPLICATIONS: The results suggest that
      central M(3) receptors are involved in peripheral pilocarpine-induced salivation
      and M(1) receptors in water intake and pressor responses. The involvement of M(3)
      receptors in water intake and pressor responses is not clear because 4-DAMP
      blocks both M(1) and M(3) receptors.

PMID- 18820714
TI  - Diastereoselectivity of the P2Y11 nucleotide receptor: mutational analysis.
AB  - BACKGROUND AND PURPOSE: The P2Y(11) receptor, a member of the group of
      metabotropic nucleotide receptors, shows a stereospecific ligand recognition of
      P(alpha)-substituted ATP derivatives (ATP-alpha-S isomers). These compounds are
      suitable candidates for the development of selective P2Y(11) receptor agonists
      that might be used as immune modulators. We have analysed the binding mode of ATP
      at the P2Y(11) receptor by molecular modeling and site-directed mutagenesis.
      Based on our recent findings, we decided to decipher the molecular determinants
      of stereoselective recognition at the P2Y(11) receptor. EXPERIMENTAL APPROACH:
      Two amino acid residues [Glu186 in the extracellular loop 2 and Arg268 in the
      transmembrane domain 6 (TM6)], which are part of the nucleotide-binding pocket,
      were selected and studied by mutational analyses. We expected these residues to
      be involved in determining the stereospecificity of the P2Y(11) receptor. KEY
      RESULTS: After mutation of Arg268 to alanine or glutamine, the stereospecific
      recognition of the ATP-alpha-S isomers at the P2Y(11) receptor was lost. In
      contrast, at the Glu186Ala receptor mutant, the stereoselective differentiation
      between these isomers was increased. On the Arg268Gln/Glu186Ala double mutant we
      observed no further effect, except for additivity in the decrease in potency of
      both isomers, as compared with the single-point mutants. CONCLUSIONS AND
      IMPLICATIONS: Our results show that the stereospecificity of the P2Y(11) receptor
      for P(alpha)-substituted ATP derivatives is largely determined by the basic
      residue Arg268 in TM6. This will allow the design of receptor-subtype selective
      ligands.

PMID- 18820716
TI  - HIV coreceptor phenotyping in the clinical setting.
AB  - The introduction of CCR5 antagonists increases the options available for
      constructing antiretroviral regimens. However, this option is coupled with the
      caveat that patients should be tested for HIV coreceptor tropism prior to
      initiating CCR5 antagonist-based therapy. Failure to screen for CXCR4 usage
      increases the risk of using an ineffective drug, thus reducing the likelihood of
      viral suppression and increasing their risk for developing antiretroviral
      resistance. This review discusses current and future methods of determining HIV
      tropism, with a focus on their utility in the clinical setting for screening
      purposes. Some of these methods include recombinant phenotypic tests, such as the
      Monogram Trofile assay, as well as genotype-based predictors, heteroduplex
      tracking assays, and flow cytometry based methods. Currently, the best evidence
      supports the use of phenotypic methods, although other methods of screening for
      HIV coreceptor usage prior to the administration of CCR5 antagonists may reduce
      costs and increase turnaround time over phenotypic methods. The presence of low
      levels of X4 virus is a challenge to all assay methods, resulting in reduced
      sensitivity in clinical, patient-derived samples when compared to clonally
      derived samples. Gaining a better understanding of the output of these assays and
      correlating them with clinical progression and therapy response will provide some
      indication on how both genotype-based, and phenotypic assays for determining HIV
      coreceptor usage can be improved. In addition, leveraging new technologies
      capable of detecting low-level minority species may provide the most significant
      advances in ensuring that individuals with low levels of dual/mixed tropic virus
      are not inadvertently prescribed CCR5 antagonists.

PMID- 18820715
TI  - Resilience to resistance of HIV-1 protease inhibitors: profile of darunavir.
AB  - The current effectiveness of HAART in the management of HIV infection is
      compromised by the emergence of extensively cross-resistant strains of HIV-1,
      requiring a significant need for new therapeutic agents. Due to its crucial role
      in viral maturation and therefore HIV-1 replication and infectivity, the HIV-1
      protease continues to be a major development target for antiretroviral therapy.
      However, new protease inhibitors must have higher thresholds to the development
      of resistance and cross-resistance. Research has demonstrated that the binding
      characteristics between a protease inhibitor and the active site of the HIV-1
      protease are key factors in the development of resistance. More specifically, the
      way in which a protease inhibitor fits within the substrate consensus volume, or
      "substrate envelope", appears to be critical. The currently available inhibitors
      are not only smaller than the native substrates, but also have a different shape.
      This difference in shape underlies observed patterns of resistance because
      primary drug-resistant mutations often arise at positions in the protease where
      the inhibitors protrude beyond the substrate envelope but are still in contact
      with the enzyme. Since all currently available protease inhibitors occupy a
      similar space (in spite of their structural differences) in the active site of
      the enzyme, the specific positions where the inhibitors protrude and contact the
      enzyme correspond to the locations where most mutations occur that give rise to
      multidrug-resistant HIV-1 strains. Detailed investigation of the structure,
      thermodynamics, and dynamics of the active site of the protease enzyme is
      enabling the identification of new protease inhibitors that more closely fit
      within the substrate envelope and therefore decrease the risk of drug resistance
      developing. The features of darunavir, the latest FDA-approved protease
      inhibitor, include its high binding affinity (Kd = 4.5 x 10-12 M) for the
      protease active site, the presence of hydrogen bonds with the backbone, and its
      ability to fit closely within the substrate envelope (or consensus volume).
      Darunavir is potent against both wild-type and protease inhibitor-resistant
      viruses in vitro, including a broad range of over 4,000 clinical isolates.
      Additionally, in vitro selection studies with wild-type HIV-1 strains have shown
      that resistance to darunavir develops much more slowly and is more difficult to
      generate than for existing protease inhibitors. Clinical studies have shown that
      darunavir administered with low-dose ritonavir (darunavir/ritonavir) provides
      highly potent viral suppression (including significant decreases in HIV viral
      load in patients with documented protease inhibitor resistance) together with
      favorable tolerability. In conclusion, as a result of its high binding affinity
      for and overall fit within the active site of HIV-1 protease, darunavir has a
      higher genetic barrier to the development of resistance and better clinical
      efficacy against multidrug-resistant HIV relative to current protease inhibitors.
      The observed efficacy, safety and tolerability of darunavir in highly treatment
      experienced patients makes darunavir an important new therapeutic option for HIV
      infected patients.

PMID- 18820717
TI  - Lipodystrophy and quality of life of HIV-infected persons.
AB  - Morphological changes induced by HIV-related lipodystrophy profoundly affect body
      image and influence health-related quality of life. Measurements of health
      related quality of life in patients with lipodystrophy are complex due to a lack
      of consensus on the definition of lipodystrophy, a lack of appropriate methods to
      capture the impact of body fat changes, and the subjective perception of those
      changes by patients. This review describes the different tools that have been
      used to assess quality of life in patients with lipodystrophy, and critically
      analyzes published papers on health-related quality of life. With regard to
      facial lipoatrophy, the most stigmatizing condition of lipodystrophy, we have
      analyzed the impact of reconstructive plastic surgery on patient-related outcomes
      and health-related quality of life. A better knowledge of the associations
      between lipodystrophy and health-related quality of life will allow us to
      understand the burden of long-term toxicities of antiretroviral therapies as well
      as to identify novel patient-related endpoints useful in assessing the efficacy
      of lipodystrophy treating programs.

PMID- 18820718
TI  - HIV-1 and the self-nonself connection: how to sleep with the enemy and be much
      better off.
AB  - Envelope-based immunogens capable of generating high titers of neutralizing
      antibodies have until now been difficult to generate, or failed to act as useful
      vaccines to prevent HIV-1 infection and disease progression. On the other hand,
      humoral immune responses to self and allogeneic cellular antigens involved in HIV
      1 docking and entry are present both in infected patients and in subjects with
      natural resistance to HIV-1 infection, where they share similarities but also
      display definite differences. By dissecting these subtle differences, crucial
      cellular and molecular markers, possibly correlated with natural resistance to
      HIV-1 and with the modulation of clinical progression in stably infected
      patients, have been identified. Here, state-of-the art knowledge on anti-self
      immune responses following infection or exposure to HIV will be reviewed. The
      possible implications of these mechanisms in the design of unconventional
      therapies aimed to counteract the peculiar HIV-1 capability to circumvent the
      immune system will be discussed.

PMID- 18820719
TI  - HIV type 1 integrase inhibitors: from basic research to clinical implications.
AB  - Similar to other retroviruses, productive infection with HIV-1 requires three key
      steps in the viral replication: (i) reverse transcription of viral genomic RNA
      into viral cDNA by the viral reverse transcriptase; (ii) integration of viral
      cDNA into host cell genome using the viral integrase; and (iii) cleavage of newly
      synthesized viral polypeptide by the viral protease into individual viral
      proteins during new virion assembly. Following their discovery, all three viral
      enzymes were considered as targets for antiretroviral drugs. However, while
      multiple reverse transcriptase and protease inhibitors have been used for more
      than 12 years to treat HIV-infected individuals, only recently has the viral
      integrase enzyme emerged as an alternative, clinically validated target to block
      HIV-1 replication. Here we review the biology of HIV-1 integration, the
      mechanisms of action and development of resistance to integrase inhibitors, and
      the latest data on the most recent clinical trials involving this promising,
      novel class of antiretroviral drugs.

PMID- 18820723
TI  - Four Classes of Structurally Unusual Peptides from Two Marine-Derived Fungi:
      Structures and Bioactivities.
AB  - The structures and biological properties of peptides produced by two genera of
      marine-derived fungi, an atypical Acremonium sp., and a Metarrhizium sp. were
      explored. The Acremonium strain was isolated from a marine sponge and has
      previously been shown by our group to produce peptides from the efrapeptin and
      RHM families. The isolation and structure elucidation of the new linear
      pentadecapeptides efrapeptins Ealpha (1), H (2) and N-methylated octapeptides
      RHM3 (3) and RHM4 (4) were carried out through a combination of 1D and 2D NMR
      techniques and tandem MS. Additional known efrapeptins E, F, G and the known
      syctalidamides A and B were also isolated. The absolute configurations of 1 - 4
      are proposed to be the same as the original compound families. The marine-sponge
      derived Metarrhizium sp. was shown to produce destruxin cyclic depsipeptides
      including A, B, B2, desmethyl B, E chlorohydrin and E2 chlorohydrin. Efrapeptins
      Ealpha (1), F and G each displayed IC(50)s of 1.3 nM against H125 cells, and
      destruxin E2 chlorohydrin displayed an IC(50) of 160 nM against HCT-116 cells. An
      initial therapeutic assessment suggested a continuous (168 h) exposure of at
      least 2 ng/ml, or a daily (24 h) exposure of at least 300 ng/ml for H125 cells
      treated with efrapeptin G, and a continuous (168 h) exposure of at least 190
      ng/ml for HCT-116 cells treated with destruxin E2 chlorohydrin, will cause 90%
      tumor cell death in vitro.

PMID- 18820724
TI  - Osteomyelitis of the mandibular symphysis caused by brown recluse spider bite.
AB  - BACKGROUND: Brown recluse spider bites cause significant trauma via their tissue
      toxic venom. Diagnosis of these injuries and envenomation is difficult and many
      times presumptive. Treatment is varied and dependent upon presentation and course
      of injury. MATERIALS AND METHODS: We present a case of a previously unreported
      incidence of osteomyelitis of the mandible as a result of a brown recluse spider
      bite. A review of the literature and discussion of diagnosis and treatment of
      brown recluse spider bites are presented. RESULTS: Osteomyelitis of the mandible
      causing a chronic wound was the presenting finding of a patient with a history of
      spider bite and exposure to brown recluse spiders. Operative debridement and
      wound closure resulted in successful treatment. Brown recluse spider envenomation
      varies in its presentation and treatment is based on the presenting clinical
      picture. CONCLUSION: Treatment regimens for brown recluse spider bite
      envenomation should include the basics of wound care. Systemic antibiotics,
      topical antimicrobials, dapsone, and surgical debridement are valuable adjuncts
      of treatment, as indicated, based on the clinical course.

PMID- 18820725
TI  - HIV-1 with multiple CCR5/CXCR4 chimeric receptor use is predictive of
      immunological failure in infected children.
AB  - BACKGROUND: HIV-1 R5 viruses are characterized by a large phenotypic variation,
      that is reflected by the mode of coreceptor use. The ability of R5 HIV-1 to
      infect target cells expressing chimeric receptors between CCR5 and CXCR4
      (R5(broad) viruses), was shown to correlate with disease stage in HIV-1 infected
      adults. Here, we ask the question whether phenotypic variation of R5 viruses
      could play a role also in mother-to-child transmission (MTCT) of HIV-1 and
      pediatric disease progression. METHODOLOGY/PRINCIPAL FINDINGS: Viral isolates
      obtained from a total of 59 HIV-1 seropositive women (24 transmitting and 35 non
      transmitting) and 28 infected newborn children, were used to infect U87.CD4 cells
      expressing wild type or six different CCR5/CXCR4 chimeric receptors. HIV-1
      isolates obtained from newborn infants had predominantly R5(narrow) phenotype (n
      = 20), but R5(broad) and R5X4 viruses were also found in seven and one case,
      respectively. The presence of R5(broad) and R5X4 phenotypes correlated
      significantly with a severe decline of the CD4+ T cells (CDC stage 3) or death
      within 2 years of age. Forty-three percent of the maternal R5 isolates displayed
      an R5(broad) phenotype, however, the presence of the R5(broad) virus was not
      predictive for MTCT of HIV-1. Of interest, while only 1 of 5 mothers with an R5X4
      virus transmitted the dualtropic virus, 5 of 6 mothers carrying R5(broad) viruses
      transmitted viruses with a similar broad chimeric coreceptor usage. Thus, the
      maternal R5(broad) phenotype was largely preserved during transmission and could
      be predictive of the phenotype of the newborn's viral variant.
      CONCLUSIONS/SIGNIFICANCE: Our results show that R5(broad) viruses are not
      hampered in transmission. When transmitted, immunological failure occurs earlier
      than in children infected with HIV-1 of R5(narrow) phenotype. We believe that
      this finding is of utmost relevance for therapeutic interventions in pediatric
      HIV-1 infection.

PMID- 18820726
TI  - Arp2/3 branched actin network mediates filopodia-like bundles formation in vitro.
AB  - During cellular migration, regulated actin assembly takes place at the cell
      leading edge, with continuous disassembly deeper in the cell interior. Actin
      polymerization at the plasma membrane results in the extension of cellular
      protrusions in the form of lamellipodia and filopodia. To understand how cells
      regulate the transformation of lamellipodia into filopodia, and to determine the
      major factors that control their transition, we studied actin self-assembly in
      the presence of Arp2/3 complex, WASp-VCA and fascin, the major proteins
      participating in the assembly of lamellipodia and filopodia. We show that in the
      early stages of actin polymerization fascin is passive while Arp2/3 mediates the
      formation of dense and highly branched aster-like networks of actin. Once
      filaments in the periphery of an aster get long enough, fascin becomes active,
      linking the filaments into bundles which emanate radially from the aster's
      surface, resulting in the formation of star-like structures. We show that the
      number of bundles nucleated per star, as well as their thickness and length, is
      controlled by the initial concentration of Arp2/3 complex ([Arp2/3]).
      Specifically, we tested several values of [Arp2/3] and found that for given
      initial concentrations of actin and fascin, the number of bundles per star, as
      well as their length and thickness are larger when [Arp2/3] is lower. Our
      experimental findings can be interpreted and explained using a theoretical scheme
      which combines Kinetic Monte Carlo simulations for aster growth, with a simple
      mechanistic model for bundles' formation and growth. According to this model,
      bundles emerge from the aster's (sparsely branched) surface layer. Bundles begin
      to form when the bending energy associated with bringing two filaments into
      contact is compensated by the energetic gain resulting from their fascin linking
      energy. As time evolves the initially thin and short bundles elongate, thus
      reducing their bending energy and allowing them to further associate and create
      thicker bundles, until all actin monomers are consumed. This process is
      essentially irreversible on the time scale of actin polymerization. Two
      structural parameters, L, which is proportional to the length of filament tips at
      the aster periphery and b, the spacing between their origins, dictate the onset
      of bundling; both depending on [Arp2/3]. Cells may use a similar mechanism to
      regulate filopodia formation along the cell leading edge. Such a mechanism may
      allow cells to have control over the localization of filopodia by recruiting
      specific proteins that regulate filaments length (e.g., Dia2) to specific sites
      along lamellipodia.

PMID- 18820727
TI  - Quantum dots for tracking dendritic cells and priming an immune response in vitro
      and in vivo.
AB  - Dendritic cells (DCs) play a key role in initiating adaptive immune response by
      presenting antigen to T cells in lymphoid organs. Here, we investigate the
      potential of quantum dots (QDs) as fluorescent nanoparticles for in vitro and in
      vivo imaging of DCs, and as a particle-based antigen-delivery system to enhance
      DC-mediated immune responses. We used confocal, two-photon, and electron
      microscopies to visualize QD uptake into DCs and compared CD69 expression, T cell
      proliferation, and IFN-gamma production by DO11.10 and OT-II T cells in vivo in
      response to free antigen or antigen-conjugated to QDs. CD11c(+) DCs avidly and
      preferentially endocytosed QDs, initially into small vesicles near the plasma
      membrane by an actin-dependent mechanism. Within 10 min DCs contained vesicles of
      varying size, motion, and brightness distributed throughout the cytoplasm. At
      later times, endocytosed QDs were compartmentalized inside lysosomes. LPS-induced
      maturation of DCs reduced the rate of endocytosis and the proportion of cells
      taking up QDs. Following subcutaneous injection of QDs in an adjuvant depot, DCs
      that had endocytosed QDs were visualized up to 400 microm deep within draining
      lymph nodes. When antigen-conjugated QDs were used, T cells formed stable
      clusters in contact with DCs. Antigen-conjugated QDs induced CD69 expression, T
      cell proliferation, and IFN-gamma production in vivo with greater efficiency than
      equivalent amounts of free antigen. These results establish QDs as a versatile
      platform for immunoimaging of dendritic cells and as an efficient nanoparticle
      based antigen delivery system for priming an immune response.

PMID- 18820728
TI  - Anti-plasmodium activity of angiotensin II and related synthetic peptides.
AB  - Plasmodium species are the causative agents of malaria, the most devastating
      insect-borne parasite of human populations. Finding and developing new drugs for
      malaria treatment and prevention is the goal of much research. Angiotensins I and
      II (ang I and ang II) and six synthetic related peptides designated Vaniceres 1-6
      (VC1-VC6) were assayed in vivo and in vitro for their effects on the development
      of the avian parasite, Plasmodium gallinaceum. Ang II and VC5 injected into the
      thoraces of the insects reduced mean intensities of infection in the mosquito
      salivary glands by 88% and 76%, respectively. Although the mechanism(s) of action
      is not completely understood, we have demonstrated that these peptides disrupt
      selectively the P.gallinaceum cell membrane. Additionally, incubation in vitro of
      sporozoites with VC5 reduced the infectivity of the parasites to their vertebrate
      host. VC5 has no observable agonist effects on vertebrates, and this makes it a
      promising drug for malaria prevention and chemotherapy.

PMID- 18820729
TI  - Cancer genes hypermethylated in human embryonic stem cells.
AB  - Developmental genes are silenced in embryonic stem cells by a bivalent histone
      based chromatin mark. It has been proposed that this mark also confers a
      predisposition to aberrant DNA promoter hypermethylation of tumor suppressor
      genes (TSGs) in cancer. We report here that silencing of a significant proportion
      of these TSGs in human embryonic and adult stem cells is associated with promoter
      DNA hypermethylation. Our results indicate a role for DNA methylation in the
      control of gene expression in human stem cells and suggest that, for genes
      repressed by promoter hypermethylation in stem cells in vivo, the aberrant
      process in cancer could be understood as a defect in establishing an unmethylated
      promoter during differentiation, rather than as an anomalous process of de novo
      hypermethylation.

PMID- 18820730
TI  - The PHA test reflects acquired T-cell mediated immunocompetence in birds.
AB  - BACKGROUND: cological immunology requires techniques to reliably measure
      immunocompetence in wild vertebrates. The PHA-skin test, involving subcutaneous
      injection of a mitogen (phytohemagglutinin, PHA) and measurement of subsequent
      swelling as a surrogate of T-cell mediated immunocompetence, has been the test of
      choice due to its practicality and ease of use in the field. However, mechanisms
      involved in local immunological and inflammatory processes provoked by PHA are
      poorly known, and its use and interpretation as an acquired immune response is
      currently debated. METHODOLOGY: Here, we present experimental work using a
      variety of parrot species, to ascertain whether PHA exposure produces larger
      secondary than primary responses as expected if the test reflects acquired
      immunocompetence. Moreover, we simultaneously quantified T-lymphocyte subsets
      (CD4(+), CD5(+) and CD8(+)) and plasma proteins circulating in the bloodstream,
      potentially involved in the immunological and inflammatory processes, through
      flow cytometry and electrophoresis. PRINCIPAL FINDINGS: Our results showed
      stronger responses after a second PHA injection, independent of species, time
      elapsed and changes in body mass of birds between first and second injections,
      thus supporting the adaptive nature of this immune response. Furthermore, the
      concomitant changes in the plasma concentrations of T-lymphocyte subsets and
      globulins indicate a causal link between the activation of the T-cell mediated
      immune system and local tissue swelling. CONCLUSIONS/SIGNIFICANCE: These findings
      justify the widespread use of the PHA-skin test as a reliable evaluator of
      acquired T-cell mediated immunocompetence in diverse biological disciplines.
      Further experimental research should be aimed at evaluating the relative role of
      innate immunocompetence in wild conditions, where the access to dietary proteins
      varies more than in captivity, and to ascertain how PHA responses relate to
      particular host-parasite interactions.

PMID- 18820731
TI  - Influenza hemagglutinin attachment to target cells: 'birds do it, we do it...'

PMID- 18820732
TI  - Temporal Stability and Authenticity of Self-Representations in Adulthood.
AB  - The temporal stability of role-specific self-representations was examined in a
      sample of 188 young, middle-aged, and older adults. Considerable stability was
      observed for all self-representations. Central self-descriptors showed
      significantly greater temporal stability than peripheral self-descriptors.
      Temporal stability of self-representations was positively associated with self
      concept clarity, self-esteem, and positive affect (PA). Age differences were
      obtained for three of the five self-representations, with older adults showing
      significantly lower stabilities for self with family, self with friend, and self
      with significant other compared to young and middle-aged adults. Assessment of
      the authenticity of adults' role-specific self-representations showed that
      greater authenticity tended to be associated with greater temporal stability.
      Authenticity and the number of positive daily events were significant positive
      predictors of the stability of self-representations.

PMID- 18820733
TI  - Metabolomic analysis and signatures in motor neuron disease.
AB  - Motor neuron diseases (MND) are a heterogeneous group of disorders that includes
      amyotrophic lateral sclerosis (ALS) and result in death of motor neurons. These
      diseases may produce characteristic perturbations of the metabolome, the
      collection of small-molecules (metabolites) present in a cell, tissue, or
      organism. To test this hypothesis, we used high performance liquid chromatography
      followed by electrochemical detection to profile blood plasma from 28 patients
      with MND and 30 healthy controls. Of 317 metabolites, 50 were elevated in
      MNDpatients and more than 70 were decreased (p < 0.05). Among the compounds
      elevated, 12 were associated with the drug Riluzole. In a subsequent study of 19
      subjects with MND who were not taking Riluzole and 33 healthy control subjects,
      six compounds were significantly elevated in MND, while the number of compounds
      with decreased concentration was similar to study 1. Our data also revealed a
      distinctive signature of highly correlated metabolites in a set of four patients,
      three of whom had lower motor neuron (LMN) disease. In both datasets we were able
      to separate MND patients from controls using multivariate regression techniques.
      These results suggest that metabolomic studies can be used to ascertain metabolic
      signatures of disease in a non-invasive fashion. Elucidation of the structures of
      signature molecules in ALS and other forms of MND should provide insight into
      aberrant biochemical pathways and may provide diagnostic markers and targets for
      drug design.

PMID- 18820734
TI  - Preparation and Characterization of Porous Gold and its Application as a Platform
      for Immobilization of Acetylcholine Esterase.
AB  - We report a method for fabrication of free-standing porous gold material with
      high surface area, and well-defined, tunable pore morphology. Porous gold is
      formed via a simple procedure which involves an acidic treatment of a
      commercially available complex white-gold alloy. We used SEM and AFM techniques
      to characterize the surface morphology, size and shape of the meso-pores as well
      as the surface roughness of the prepared porous gold samples. Formation of self
      assembled monolayers of a flavin sulfide on the gold surface was used to estimate
      the total surface area of porous gold material. The monolayers were found to be
      electrochemically active by cyclic and square-wave voltammetry. It was found that
      24 hour HNO(3) treatment gave a 12,400 times surface enlargement and resulted in
      a surface area of 14.2 m(2)/g, whereas 72 hour HNO(3) treatment resulted in a
      6900 times surface enlargement and a surface area of 8.7 m(2)/g. In addition, the
      enzyme acetylcholine esterase was immobilized on the different porous gold
      surfaces in order to demonstrate biocompatibility of the porous gold material.
      Kinetic parameters and the amount of the immobilized acetylcholine esterase were
      determined.

PMID- 18820735
TI  - Effects of Hofmeister Anions on the LCST of PNIPAM as a Function of Molecular
      Weight.
AB  - The effect of a series of sodium salts on the lower critical solution temperature
      (LCST) of poly(N-isopropylacrylamide), PNIPAM, was investigated as a function of
      molecular weight and polymer concentration with a temperature gradient
      microfluidic device under a dark-field microscope. In solutions containing
      sufficient concentrations of kosmotropic anions, the phase transition of PNIPAM
      was resolved into two separate steps for higher molecular weight samples. The
      first step of this two step transition was found to be sensitive to the polymer's
      molecular weight and solution concentration, while the second step was not.
      Moreover, the binding of chaotropic anions to the polymer was also influenced by
      molecular weight. Both sets of results could be explained by the formation of
      intramolecular and intermolecular hydrogen-bonding between polymer chains. By
      contrast, the hydrophobic hydration of the isopropyl moieties and polymer
      backbone was found to be unaffected by either the polymer's molecular weight or
      solution concentration.

PMID- 18820736
TI  - Nanoparticle-based Photosensitizers Under CW Infrared Excitation.

PMID- 18820737
TI  - Signal regulatory protein alpha negatively regulates beta2 integrin-mediated
      monocyte adhesion, transendothelial migration and phagocytosis.
AB  - BACKGROUND: Signal regulate protein alpha (SIRPalpha) is involved in many
      functional aspects of monocytes. Here we investigate the role of SIRPalpha in
      regulating beta(2) integrin-mediated monocyte adhesion, transendothelial
      migration (TEM) and phagocytosis. METHODOLOGY/PRINCIPAL FINDINGS: THP-1
      monocytes/macropahges treated with advanced glycation end products (AGEs)
      resulted in a decrease of SIRPalpha expression but an increase of beta(2)
      integrin cell surface expression and beta(2) integrin-mediated adhesion to tumor
      necrosis factor-alpha (TNFalpha)-stimulated human microvascular endothelial cell
      (HMEC-1) monolayers. In contrast, SIRPalpha overexpression in THP-1 cells showed
      a significant less monocyte chemotactic protein-1 (MCP-1)-triggered cell surface
      expression of beta(2) integrins, in particular CD11b/CD18. SIRPalpha
      overexpression reduced beta(2) integrin-mediated firm adhesion of THP-1 cells to
      either TNFalpha-stimulated HMEC-1 monolayers or to immobilized intercellular
      adhesion molecule-1 (ICAM-1). SIRPalpha overexpression also reduced MCP-1
      initiated migration of THP-1 cells across TNFalpha-stimulated HMEC-1 monolayers.
      Furthermore, beta(2) integrin-mediated THP-1 cell spreading and actin
      polymerization in response to MCP-1, and phagocytosis of bacteria were both
      inhibited by SIRPalpha overexpression. CONCLUSIONS/SIGNIFICANCE: SIRPalpha
      negatively regulates beta(2) integrin-mediated monocyte adhesion,
      transendothelial migration and phagocytosis, thus may serve as a critical
      molecule in preventing excessive activation and accumulation of monocytes in the
      arterial wall during early stage of atherosclerosis.

PMID- 18820738
TI  - Therapeutic effect of a novel oxazolidinone, DA-7867, in BALB/c mice infected
      with Nocardia brasiliensis.
AB  - BACKGROUND: Mycetoma is a chronic infectious disease of tropical and subtropical
      countries. It is produced by true fungi and actinobacteria. In Mexico, Nocardia
      brasiliensis is the main causative agent of mycetoma, producing about 86% of the
      cases; the gold standard for the therapy of mycetoma by N. brasiliensis is the
      use of sulfonamides which give a 70% cure rate. The addition of amikacin to this
      regime increases to 95% the cure rate; however, the patients have to be monitored
      for creatinine clearance and audiometry studies because of the potential
      development of side effects. Because of that it is important to search for new
      active compounds. In the present work, we evaluated the in vivo effect of DA
      7867, an experimental oxazolidinone, on the development of experimental mycetomas
      by N. brasiliensis in BALB/c mice. METHODOLOGY/PRINCIPAL FINDINGS: In order to
      determine the optimal dose utilized to apply to the animals, we first determined
      by HPLC the plasma levels using several concentrations of the compounds. Based on
      these results, we used 10 and 25 mg/kg subcutaneously every 24 hr; DA-7867 was
      also supplied in the drinking water at a calculated dose of 25 mg/kg. As a
      control we utilized linezolid at 25 mg/kg, a compound active in murine and human
      infections, three times a day. The mice were infected in the right footpad with a
      young culture of N. brasiliensis HUJEG-1, and one week later we started the
      application of the antimicrobials for six more weeks. After that we compared the
      development of lesions in the groups injected with saline solution or with the
      antimicrobials; the results were analyzed by the variance ANOVA test. DA-7867 was
      able to reduce the production of lesions at 25 mg/kg, when given either
      subcutaneously or in the drinking water. CONCLUSIONS/SIGNIFICANCE: The
      experimental oxazolidinone DA-7867 is active in vivo against N. brasiliensis,
      which opens the possibility of using this drug once it is accepted for human
      application. Since oxazolidinones seem to be active against a wide spectrum of
      actinobacteria, it is possible they could be used in human cases of mycetoma by
      other actinomycetales, such as Streptomyces somaliensis, highly prevalent in
      Sudan, or Actinomadura madurae and A. pelletieri, which are commonly observed in
      Africa and India.

PMID- 18820739
TI  - Elimination of Schistosoma mansoni Adult Worms by Rhesus Macaques: Basis for a
      Therapeutic Vaccine?
AB  - BACKGROUND: Among animal models of schistosomiasis, the rhesus macaque is unique
      in that an infection establishes but egg excretion rapidly diminishes,
      potentially due to loss of adult worms from the portal system via shunts or death
      by immune attack. PRINCIPAL FINDINGS: To investigate this, six rhesus macaques
      were exposed to Schistosoma mansoni cercariae and the infection monitored until
      portal perfusion at 18 weeks. Despite a wide variation in worm numbers recovered,
      fecal egg output and circulating antigen levels indicated that a substantial
      population had established in all animals. Half the macaques had portal
      hypertension but only one had portacaval shunts, ruling out translocation to the
      lungs as the reason for loss of adult burden. Many worms had a shrunken and
      pallid appearance, with degenerative changes in intestines and reproductive
      organs. Tegument, gut epithelia and muscles appeared cytologically intact but the
      parenchyma was virtually devoid of content. An early and intense IgG production
      correlated with low worm burden at perfusion, and blood-feeding worms cultured in
      the presence of serum from these animals had stunted growth. Using
      immunoproteomics, gut digestive enzymes, tegument surface hydrolases and
      antioxidant enzymes were identified as targets of IgG in the high responder
      animals. SIGNIFICANCE: It appears that worms starve to death after cessation of
      blood feeding, as a result of antibody-mediated processes. We suggest that
      proteins in the three categories above, formulated to trigger the appropriate
      mechanisms operating in rhesus macaques, would have both prophylactic and
      therapeutic potential as a human vaccine.

PMID- 18820740
TI  - Hookworm-related anaemia among pregnant women: a systematic review.
AB  - BACKGROUND AND OBJECTIVES: Hookworm infection is among the major causes of
      anaemia in poor communities, but its importance in causing maternal anaemia is
      poorly understood, and this has hampered effective lobbying for the inclusion of
      anthelmintic treatment in maternal health packages. We sought to review existing
      evidence on the role of hookworm as a risk factor for anaemia among pregnant
      women. We also estimate the number of hookworm infections in pregnant women in
      sub-Saharan Africa (SSA). METHODS: Structured searches using MEDLINE and EMBASE
      as well as manual searches of reference lists were conducted, and unpublished
      data were obtained by contacting authors. Papers were independently reviewed by
      two authors, and relevant data were extracted. We compared haemoglobin
      concentration (Hb) according to intensity of hookworm infection and calculated
      standardised mean differences and 95% confidence intervals. To estimate the
      number of pregnant women, we used population surfaces and a spatial model of
      hookworm prevalence. FINDINGS: One hundred and five reports were screened and 19
      were eligible for inclusion: 13 cross-sectional studies, 2 randomised controlled
      trials, 2 non-randomised treatment trials and 2 observational studies. Comparing
      uninfected women and women lightly (1-1,999 eggs/gram [epg]) infected with
      hookworm, the standardised mean difference (SMD) was -0.24 (95% CI: -0.36 to 
      0.13). The SMD between women heavily (4000+ epg) infected and those lightly
      infected was -0.57 (95% CI: -0.87 to -0.26). All identified intervention studies
      showed a benefit of deworming for maternal or child health, but since a variety
      of outcomes measures were employed, quantitative evaluation was not possible. We
      estimate that 37.7 million women of reproductive age in SSA are infected with
      hookworm in 2005 and that approximately 6.9 million pregnant women are infected.
      CONCLUSIONS: Evidence indicates that increasing hookworm infection intensity is
      associated with lower haemoglobin levels in pregnant women in poor countries.
      There are insufficient data to quantify the benefits of deworming, and further
      studies are warranted. Given that between a quarter and a third of pregnant women
      in SSA are infected with hookworm and at risk of preventable hookworm-related
      anaemia, efforts should be made to increase the coverage of anthelmintic
      treatment among pregnant women.

PMID- 18820741
TI  - Impact of long-term treatment with ivermectin on the prevalence and intensity of
      soil-transmitted helminth infections.
AB  - BACKGROUND: Control of soil-transmitted helminth (STH) infections relies on the
      periodic and long-term administration of anthelmintic drugs to high-risk groups,
      particularly school-age children living in endemic areas. There is limited data
      on the effectiveness of long-term periodic anthelmintic treatment on the
      prevalence of STHs, particularly from operational programmes. The current study
      investigated the impact of 15 to 17 years of treatment with the broad-spectrum
      anthelmintic ivermectin, used for the control of onchocerciasis, on STH
      prevalence and intensity in school-age and pre-school children. METHODS AND
      FINDINGS: A cross-sectional study was conducted in communities that had received
      annual or twice-annual ivermectin treatments and geographically adjacent
      communities that had not received treatment in two districts of Esmeraldas
      Province in Ecuador. Stool samples were collected from school-age children and
      examined for STH infection using the Kato-Katz and formol-ether concentration
      methods. Samples were collected also from pre-school children and examined by the
      formol-ether concentration method. Data on risk factors for STH infection were
      collected by parental questionnaire. We sampled a total of 3,705 school-age
      children (6-16 years) from 31 treated and 27 non-treated communities, and 1,701
      pre-school children aged 0-5 years from 18 treated and 18 non-treated
      communities. Among school-age children, ivermectin treatment had significant
      effects on the prevalence (adjusted OR = 0.06, 95% CI 0.03-0.14) and intensity of
      Trichuris trichiura infection (adjusted RR = 0.28, 95% CI 0.11-0.70), but
      appeared to have no impact on Ascaris lumbricoides or hookworm infection. Reduced
      prevalence and intensities of T. trichiura infection were observed among children
      not eligible to receive ivermectina, providing some evidence of reduced
      transmission of T. trichiura infection in communities receiving mass ivermectin
      treatments. CONCLUSION: Annual and twice-annual treatments with ivermectin over a
      period of up to 17 years may have had a significant impact on T. trichiura
      infection. The present data indicate that the long-term control of onchocerciasis
      with ivermectin may provide additional health benefits by reducing infections
      with trichuriasis. The addition of a second anthelmintic drug such as albendazole
      may be useful for a long-term effect on A. lumbricoides infection.

PMID- 18820742
TI  - Hyaluronidase of bloodsucking insects and its enhancing effect on leishmania
      infection in mice.
AB  - BACKGROUND: Salivary hyaluronidases have been described in a few bloodsucking
      arthropods. However, very little is known about the presence of this enzyme in
      various bloodsucking insects and no data are available on its effect on
      transmitted microorganisms. Here, we studied hyaluronidase activity in thirteen
      bloodsucking insects belonging to four different orders. In addition, we assessed
      the effect of hyaluronidase coinoculation on the outcome of Leishmania major
      infection in BALB/c mice. PRINCIPAL FINDINGS: High hyaluronidase activity was
      detected in several Diptera tested, namely deer fly Chrysops viduatus, blackflies
      Odagmia ornata and Eusimilium latipes, mosquito Culex quinquefasciatus, biting
      midge Culicoides kibunensis and sand fly Phlebotomus papatasi. Lower activity was
      detected in cat flea Ctenocephalides felis. No activity was found in kissing bug
      Rhodnius prolixus, mosquitoes Anopheles stephensi and Aedes aegypti, tse-tse fly
      Glossina fuscipes, stable fly Stomoxys calcitrans and human louse Pediculus
      humanus. Hyaluronidases of different insects vary substantially in their
      molecular weight, the structure of the molecule and the sensitivity to reducing
      conditions or sodium dodecyl sulphate. Hyaluronidase exacerbates skin lesions
      caused by Leishmania major; more severe lesions developed in mice where L. major
      promastigotes were coinjected with hyaluronidase. CONCLUSIONS: High hyaluronidase
      activities seem to be essential for insects with pool-feeding mode, where they
      facilitate the enlargement of the feeding lesion and serve as a spreading factor
      for other pharmacologically active compounds present in saliva. As this enzyme is
      present in all Phlebotomus and Lutzomyia species studied to date, it seems to be
      one of the factors responsible for enhancing activity present in sand fly saliva.
      We propose that salivary hyaluronidase may facilitate the spread of other vector
      borne microorganisms, especially those transmitted by insects with high
      hyaluronidase activity, namely blackflies (Simuliidae), biting midges
      (Ceratopogonidae) and horse flies (Tabanidae).

PMID- 18820743
TI  - Toward comprehensive interventions to improve the health of women of reproductive
      age.

PMID- 18820745
TI  - RNA interference of Trypanosoma brucei cathepsin B and L affects disease
      progression in a mouse model.
AB  - We investigated the roles played by the cysteine proteases cathepsin B and
      cathepsin L (brucipain) in the pathogenesis of Trypansoma brucei brucei in both
      an in vivo mouse model and an in vitro model of the blood-brain barrier.
      Doxycycline induction of RNAi targeting cathepsin B led to parasite clearance
      from the bloodstream and prevent a lethal infection in the mice. In contrast, all
      mice infected with T. brucei containing the uninduced Trypanosoma brucei
      cathepsin B (TbCatB) RNA construct died by day 13. Induction of RNAi against
      brucipain did not cure mice from infection; however, 50% of these mice survived
      60 days longer than uninduced controls. The ability of T. b. brucei to cross an
      in vitro model of the human blood-brain barrier was also reduced by brucipain
      RNAi induction. Taken together, the data suggest that while TbCatB is the more
      likely target for the development of new chemotherapy, a possible role for
      brucipain is in facilitating parasite entry into the brain.

PMID- 18820744
TI  - Evidence for positive selection in putative virulence factors within the
      Paracoccidioides brasiliensis species complex.
AB  - Paracoccidioides brasiliensis is a dimorphic fungus that is the causative agent
      of paracoccidioidomycosis, the most important prevalent systemic mycosis in Latin
      America. Recently, the existence of three genetically isolated groups in P.
      brasiliensis was demonstrated, enabling comparative studies of molecular
      evolution among P. brasiliensis lineages. Thirty-two gene sequences coding for
      putative virulence factors were analyzed to determine whether they were under
      positive selection. Our maximum likelihood-based approach yielded evidence for
      selection in 12 genes that are involved in different cellular processes. An in
      depth analysis of four of these genes showed them to be either antigenic or
      involved in pathogenesis. Here, we present evidence indicating that several
      replacement mutations in gp43 are under positive balancing selection. The other
      three genes (fks, cdc42 and p27) show very little variation among the P.
      brasiliensis lineages and appear to be under positive directional selection. Our
      results are consistent with the more general observations that selective
      constraints are variable across the genome, and that even in the genes under
      positive selection, only a few sites are altered. We present our results within
      an evolutionary framework that may be applicable for studying adaptation and
      pathogenesis in P. brasiliensis and other pathogenic fungi.

PMID- 18820746
TI  - The burden of trachoma in Ayod County of Southern Sudan.
AB  - BACKGROUND: Blindness due to trachoma is avoidable through Surgery, Antibiotics,
      Facial hygiene and Environmental improvements (SAFE). Recent surveys have shown
      trachoma to be a serious cause of blindness in Southern Sudan. We conducted this
      survey in Ayod County of Jonglei State to estimate the need for intervention
      activities to eliminate blinding trachoma. METHODOLOGY AND FINDINGS: A cross
      sectional two-stage cluster random survey was conducted in November 2006. All
      residents of selected households were clinically assessed for trachoma using the
      World Health Organization (WHO) simplified grading scheme. A total of 2,335
      people from 392 households were examined, of whom 1,107 were over 14 years of
      age. Prevalence of signs of active trachoma in children 1-9 years of age was:
      trachomatous inflammation follicular (TF) = 80.1% (95% confidence interval [CI],
      73.9-86.3); trachomatous inflammation intense (TI) = 60.7% (95% CI, 54.6-66.8);
      and TF and/or TI (active trachoma) = 88.3% (95% CI, 83.7-92.9). Prevalence of
      trachomatous trichiasis (TT) was 14.6% (95% CI, 10.9-18.3) in adults over 14
      years of age; 2.9% (95% CI, 0.4-5.3) in children 1-14 years of age; and 8.4% (95%
      CI, 5.5-11.3) overall. The prevalence of corneal opacity in persons over 14 years
      of age with TT was 6.4% (95% CI, 4.5-8.3). No statistically significant
      difference was observed in the prevalence of trachoma signs between genders.
      Trachoma affected almost all households surveyed: 384/392 (98.0%) had at least
      one person with active trachoma and 130 (33.2%) had at least one person with
      trichiasis. CONCLUSIONS: Trachoma is an unnecessary public health problem in
      Ayod. The high prevalence of active trachoma and trichiasis confirms the severe
      burden of blinding trachoma found in other post-conflict areas of Southern Sudan.
      Based on WHO recommended thresholds, all aspects of the SAFE strategy are
      indicated to eliminate blinding trachoma in Ayod.

PMID- 18820747
TI  - The neglected tropical diseases of Latin America and the Caribbean: a review of
      disease burden and distribution and a roadmap for control and elimination.
AB  - The neglected tropical diseases (NTDs) represent some of the most common
      infections of the poorest people living in the Latin American and Caribbean
      region (LAC). Because they primarily afflict the disenfranchised poor as well as
      selected indigenous populations and people of African descent, the NTDs in LAC
      are largely forgotten diseases even though their collective disease burden may
      exceed better known conditions such as of HIV/AIDS, tuberculosis, or malaria.
      Based on their prevalence and healthy life years lost from disability, hookworm
      infection, other soil-transmitted helminth infections, and Chagas disease are the
      most important NTDs in LAC, followed by dengue, schistosomiasis, leishmaniasis,
      trachoma, leprosy, and lymphatic filariasis. On the other hand, for some
      important NTDs, such as leptospirosis and cysticercosis, complete disease burden
      estimates are not available. The NTDs in LAC geographically concentrate in 11
      different sub-regions, each with a distinctive human and environmental ecology.
      In the coming years, schistosomiasis could be eliminated in the Caribbean and
      transmission of lymphatic filariasis and onchocerciasis could be eliminated in
      Latin America. However, the highest disease burden NTDs, such as Chagas disease,
      soil-transmitted helminth infections, and hookworm and schistosomiasis co
      infections, may first require scale-up of existing resources or the development
      of new control tools in order to achieve control or elimination. Ultimately, the
      roadmap for the control and elimination of the more widespread NTDs will require
      an inter-sectoral approach that bridges public health, social services, and
      environmental interventions.

PMID- 18820748
TI  - Needles in the EST haystack: large-scale identification and analysis of excretory
      secretory (ES) proteins in parasitic nematodes using expressed sequence tags
      (ESTs).
AB  - BACKGROUND: Parasitic nematodes of humans, other animals and plants continue to
      impose a significant public health and economic burden worldwide, due to the
      diseases they cause. Promising antiparasitic drug and vaccine candidates have
      been discovered from excreted or secreted (ES) proteins released from the
      parasite and exposed to the immune system of the host. Mining the entire
      expressed sequence tag (EST) data available from parasitic nematodes represents
      an approach to discover such ES targets. METHODS AND FINDINGS: In this study, we
      predicted, using EST2Secretome, a novel, high-throughput, computational workflow
      system, 4,710 ES proteins from 452,134 ESTs derived from 39 different species of
      nematodes, parasitic in animals (including humans) or plants. In total, 2,632,
      786, and 1,292 ES proteins were predicted for animal-, human-, and plant
      parasitic nematodes. Subsequently, we systematically analysed ES proteins using
      computational methods. Of these 4,710 proteins, 2,490 (52.8%) had orthologues in
      Caenorhabditis elegans, whereas 621 (13.8%) appeared to be novel, currently
      having no significant match to any molecule available in public databases. Of the
      C. elegans homologues, 267 had strong "loss-of-function" phenotypes by RNA
      interference (RNAi) in this nematode. We could functionally classify 1,948
      (41.3%) sequences using the Gene Ontology (GO) terms, establish pathway
      associations for 573 (12.2%) sequences using Kyoto Encyclopaedia of Genes and
      Genomes (KEGG), and identify protein interaction partners for 1,774 (37.6%)
      molecules. We also mapped 758 (16.1%) proteins to protein domains including the
      nematode-specific protein family "transthyretin-like" and "chromadorea ALT,"
      considered as vaccine candidates against filariasis in humans. CONCLUSIONS: We
      report the large-scale analysis of ES proteins inferred from EST data for a range
      of parasitic nematodes. This set of ES proteins provides an inventory of known
      and novel members of ES proteins as a foundation for studies focused on
      understanding the biology of parasitic nematodes and their interactions with
      their hosts, as well as for the development of novel drugs or vaccines for
      parasite intervention and control.

PMID- 18820749
TI  - Reports on the prevalence of clinical conditions are more convincing when
      supported by objective evidence.

PMID- 18820750
TI  - Chlamydia trachomatis ompA variants in trachoma: what do they tell us?
AB  - BACKGROUND: Trachoma, caused by Chlamydia trachomatis (Ct), is the leading
      infectious cause of blindness. Sequence-based analysis of the multiple strains
      typically present in endemic communities may be informative for epidemiology,
      transmission, response to treatment, and understanding the host response.
      METHODS: Conjunctival and nasal samples from a Gambian community were evaluated
      before and 2 months after mass azithromycin treatment. Samples were tested for Ct
      by Amplicor, with infection load determined by quantitative PCR (qPCR). ompA
      sequences were determined and their diversity analysed using frequency-based
      tests of neutrality. RESULTS: Ninety-five of 1,319 (7.2%) individuals from 14
      villages were infected with Ct at baseline. Two genovars (A and B) and 10
      distinct ompA genotypes were detected. Two genovar A variants (A1 and A2)
      accounted for most infections. There was an excess of rare ompA mutations, not
      sustained in the population. Post-treatment, 76 (5.7%) individuals had Ct
      infection with only three ompA genotypes present. In 12 of 14 villages, infection
      had cleared, while in two it increased, probably due to mass migration. Infection
      qPCR loads associated with infection were significantly greater for A1 than for
      A2. Seven individuals had concurrent ocular and nasal infection, with divergent
      genotypes in five. CONCLUSIONS: The number of strains was substantially reduced
      after mass treatment. One common strain was associated with higher infection
      loads. Discordant genotypes in concurrent infection may indicate distinct
      infections at ocular and nasal sites. Population genetic analysis suggests the
      fleeting appearance of rare multiple ompA variants represents purifying selection
      rather than escape variants from immune pressure. Genotyping systems accessing
      extra-ompA variation may be more informative.

PMID- 18820753
TI  - Isoprenoid-like alkylations in polyketide biosynthesis.
AB  - Polyketides are secondary metabolites biosynthesized by the iterative Claisen
      condensation of malonate units. Despite utilizing only a small set of biochemical
      transformations, the polyketide biosynthetic machinery yields products of
      striking structural complexity and diversity. Recently, a new polyketide
      alkylation pathway was characterized that allows access to "beta-branched"
      structures. This Highlight will describe this alkylation sequence, with special
      emphasis on its parallels to isoprenoid biosynthesis from primary metabolism and
      the scope of structures accessible via this pathway.

PMID- 18820754
TI  - Tedanolide and the evolution of polyketide inhibitors of eukaryotic protein
      synthesis.
AB  - This Highlight covers the chemical and biological studies regarding a set of
      polyketide inhibitors of eukaryotic protein synthesis related to the marine
      derived cytotoxic agent tedanolide.

PMID- 18820755
TI  - Syntheses of the tedanolides.
AB  - This Highlight covers the synthetic contributions leading to the syntheses of
      tedanolide and 13-deoxytedanolide or the corresponding macrolactones,
      respectively. Additionally, the first SAR data for 13-deoxytedanolide (published
      by Fusetani) are presented.

PMID- 18820756
TI  - Triterpenoids from the Schisandraceae family.
AB  - Over the past 30 years, the family Schisandraceae has received considerable
      attention in chemical and biological studies. In particular, the discovery of a
      series of highly oxygenated triterpenoids with different skeletons has further
      increased the interest in this family. This review covers the structures,
      proposed biosynthetic pathways, total synthesis and biological activities of
      these and other triterpenoids from the plants of the family Schisandraceae. There
      are 100 references.

PMID- 18820757
TI  - Scaffold diversity of natural products: inspiration for combinatorial library
      design.
AB  - Natural products contain scaffold structures that can be systematically exploited
      for the design of combinatorial compound libraries with druglike properties. We
      review approaches for scaffold identification, and compare properties and
      pharmacophoric features of drugs and natural products. In particular, an
      application of the self-organizing map technique is presented for natural product
      derived compound and library design.

PMID- 18820758
TI  - New methods for stereochemical determination of complex polyketides:
      configurational assignment of novel metabolites from myxobacteria.
AB  - An overview on recently developed methods for the stereochemical determination of
      complex polyketides is given and NMR-spectroscopic, computational, biosynthetic
      and synthetic methods are discussed. These methods are presented in their
      applications to structurally novel polyketide classes from myxobacteria.

PMID- 18820759
TI  - The chemistry and biology of organic guanidine derivatives.
AB  - Organic guanidine compounds are reviewed, with emphasis on natural products
      isolation, identification, synthesis and biological activities. The literature
      survey includes purely synthetic guanidine derivatives, guanidine alkaloids and
      non-ribosomal peptides from bacteria and cyanobacteria, as well as related
      compounds isolated from marine and terrestrial invertebrates and higher plants.

PMID- 18820760
TI  - Natural products from true mangrove flora: source, chemistry and bioactivities.
AB  - The mangrove flora is a diverse group of salt-tolerant plants growing in tropical
      and subtropical intertidal estuarine zones. This review summarizes the source,
      chemistry and bioactivities of natural products from true mangrove species
      worldwide. It includes 349 metabolites and 150 references. The molecular
      phylogeny and chemotaxonomy of true mangrove plants is discussed.

PMID- 18820761
TI  - Narratives: use in qualitative health-related research.
AB  - The present bibliographic review followed a path through several chains of
      thought concerned with studying narratives. Some classical studies on narrative
      structure with origins within literature, history, communications theory and
      psychoanalysis were analyzed with the aim of exploring whether their categories
      and concepts would be methodologically applicable to qualitative health-related
      research. In the conclusions, the potential for using narratives to study
      situations in which there is interest in mediations between experience and
      language, between structure and events, between subjects and collective groups or
      between memory and political action are highlighted. These are questions that
      traditionally are of interest within Brazilian public health with regard to the
      field of "Policy, Planning and Management".

PMID- 18820762
TI  - Relationship between the quality of life and the severity of obstructive sleep
      apnea syndrome.
AB  - The effects of sleep disorders on the quality of life (QOL) have been documented
      in the literature. Excessive sleepiness and altered circadian rhythms may
      negatively affect ability to learn, employment, and interpersonal relations, and
      directly degrade QOL. The objective of the present study was to evaluate the
      impact of obstructive sleep apnea syndrome of varying severity on QOL. The study
      was conducted on 1892 patients aged 18 years or older referred by a physician to
      the Sleep Institute, Sao Paulo, with complaints related to apnea (snoring,
      excessive daytime sleepiness, hyperarousal, and fatigue). They were submitted to
      overnight polysomnography for the diagnosis of sleep disorders from August 2005
      through April 2006. The patients completed the Epworth Sleepiness Scale and QOL
      SF-36 sleep questionnaires. They were classified as non-physically active and
      physically active and not-sleepy and sleepy and the results of polysomnography
      were analyzed on the basis of the apnea hypopnea index (AHI). The apneic subjects
      showed a reduction in QOL which was proportional to severity. There was a
      significant decrease in all domains (physical functioning, role physical
      problems, bodily pain, general health perceptions, vitality, social functioning,
      emotional problems, general mental health) for apneics with AHI >30, who
      generally were sleepy and did not participate in physical activities (P < 0.05).
      The present study provides evidence that the impact of sleep disorders on QOL in
      apneics is not limited to excessive daytime sleepiness and that physical activity
      can contribute to reducing the symptoms. Thus, exercise should be considered as
      an adjunct interventional strategy in the management of obstructive sleep apnea
      syndrome.

PMID- 18820763
TI  - Measurement of annexin V uptake and lactadherin labeling for the quantification
      of apoptosis in adherent Tca8113 and ACC-2 cells.
AB  - Phosphatidylserine (PS) exposure occurs during the cell death program and
      fluorescein-labeled lactadherin permits the detection of PS exposure earlier than
      annexin V in suspended cell lines. Adherent cell lines were studied for this
      apoptosis-associated phenomenon to determine if PS probing methods are reliable
      because specific membrane damage may occur during harvesting. Apoptosis was
      induced in the human tongue squamous carcinoma cell line (Tca8113) and the
      adenoid cystic carcinoma cell line (ACC-2) by arsenic trioxide. Cells were
      harvested with a modified procedure and labeled with lactadherin and/or annexin
      V. PS exposure was localized by confocal microscopy and apoptosis was quantified
      by flow cytometry. The detachment procedure without trypsinization did not induce
      cell damage. In competition binding experiments, phospholipid vesicles competed
      for more than 95 and 90% of lactadherin but only about 75 and 70% of annexin V
      binding to Tca8113 and ACC-2 cells. These data indicate that PS exposure occurs
      in three stages during the cell death program and that fluorescein-labeled
      lactadherin permitted the detection of early PS exposure. A similar pattern of PS
      exposure has been observed in two malignant cell lines with different adherence,
      suggesting that this pattern of PS exposure is common in adherent cells. Both
      lactadherin and annexin V could be used in adherent Tca8113 and ACC-2 cell lines
      when an appropriate harvesting procedure was used. Lactadherin is more sensitive
      than annexin V for the detection of PS exposure as the physical structure of PS
      in these blebs and condensed apoptotic cell surface may be more conducive to
      binding lactadherin than annexin V.

PMID- 18820764
TI  - Solubilization of human erythrocyte membranes by ASB detergents.
AB  - Understanding the membrane solubilization process and finding effective
      solubilizing agents are crucial challenges in biochemical research. Here we
      report results on the interaction of the novel linear alkylamido propyl dimethyl
      amino propanosulfonate detergents, ASB-14 and ASB-16, with human erythrocyte
      membranes. An estimation of the critical micelle concentration of these
      zwitterionic detergents (ASB-14 = 100 microM and ASB-16 = 10 microM) was obtained
      using electron paramagnetic resonance. The amount of proteins and cholesterol
      solubilized from erythrocytes by these detergents was then determined. The
      hemolytic activities of the ASB detergents were assayed and the detergent/lipid
      molar ratios for the onset of hemolysis (Re sat) and total lysis (Re sol) were
      calculated, allowing the determination of the membrane binding constants (Kb).
      ASB-14 presented lower membrane affinity (Kb = 7050 M(-1)) than ASB-16 (Kb =
      15610 M(-1)). The amount of proteins and cholesterol solubilized by both ASB
      detergents was higher while Re sat values (0.22 and 0.08 detergent/lipid for ASB
      14 and ASB-16, respectively) were smaller than those observed with the classic
      detergents CHAPS and Triton X-100. These results reveal that, besides their well
      known use as membrane protein solubilizers to enhance the resolution of two
      dimensional electrophoresis/mass spectrometry, ASB-14 and ASB-16 are strong
      hemolytic agents. We propose that the physicochemical properties of ASB
      detergents determine their membrane disruption efficiency and can help to explain
      the improvement in the solubilization of membrane proteins, as reported in the
      literature.

PMID- 18820765
TI  - Attenuation of phosphamidon-induced oxidative stress and immune dysfunction in
      rats treated with N-acetylcysteine.
AB  - The effect of N-acetylcysteine, a thiolic antioxidant, on attenuation of
      phosphamidon-induced oxidative stress and immune dysfunction was evaluated in
      adult male Wistar rats weighing 200-250 g. Rats were divided into four groups, 8
      animals/group, and treated with phosphamidon, N-acetylcysteine or the combination
      of both for 28 days. Oral administration of phosphamidon (1.74 mg/kg), an
      organophosphate insecticide, increased serum malondialdehyde (3.83 +/- 0.18 vs
      2.91 +/- 0.24 nmol/mL; P < 0.05) and decreased erythrocyte superoxide dismutase
      (567.8 +/- 24.36 vs 749.16 +/- 102.61 U/gHb; P < 0.05), catalase activity (1.86
      +/- 0.18 vs 2.43 +/- 0.08 U/gHb; P < 0.05) and whole blood glutathione levels
      (1.25 +/- 0.21 vs 2.28 +/- 0.08 mg/gHb; P < 0.05) showing phosphamidon-induced
      oxidative stress. Phosphamidon exposure markedly suppressed humoral immune
      response as assessed by antibody titer to ovalbumin (4.71 +/- 0.51 vs 8.00 +/-
      0.12 -log(2); P < 0.05), and cell-mediated immune response as assessed by
      leukocyte migration inhibition (25.24 +/- 1.04 vs 70.8 +/- 1.09%; P < 0.05) and
      macrophage migration inhibition (20.38 +/- 0.99 vs 67.16 +/- 5.30%; P < 0.05)
      response. Phosphamidon exposure decreased IFN-small u, Cyrillic levels (40.7 +/-
      3.21 vs 55.84 +/- 3.02 pg/mL; P < 0.05) suggesting a profound effect of
      phosphamidon on cell-mediated immune response. A phosphamidon-induced increase in
      TNF-alpha level (64.19 +/- 6.0 vs 23.16 +/- 4.0 pg/mL; P < 0.05) suggests a
      contributory role of immunocytes in oxidative stress. Co-administration of N
      acetylcysteine (3.5 mmol/kg, orally) with phosphamidon attenuated the adverse
      effects of phosphamidon. These findings suggest that oral N-acetylcysteine
      treatment exerts protective effect and attenuates free radical injury and immune
      dysfunction caused by subchronic phosphamidon exposure.

PMID- 18820766
TI  - ABCB1 C1236T, G2677T/A and C3435T polymorphisms in systemic lupus erythematosus
      patients.
AB  - P-glycoprotein (Pgp), the ABCB1 gene product, acts as an efflux pump that
      transports a large variety of substrates and is a mechanism of cell protection
      against xenobiotics. An increasing number of studies have shown that some ABCB1
      polymorphisms may affect Pgp expression and activity, as well as affecting the
      development and susceptibility to diseases and pharmacological response. High
      activity of Pgp has been detected in systemic lupus erythematosus (SLE) patients.
      The C1236T, G2677T/A, and C3435T are the most commonly studied single nucleotide
      polymorphisms in the ABCB1 gene. Therefore, their frequencies were determined in
      Brazilian individuals with European ancestry (N = 143) and in SLE patients (N =
      137). Genotyping was performed by PCR-RFLP analysis using specific primers
      followed by incubation with the appropriate restriction enzymes. The resulting
      DNA fragments were visualized on agarose or polyacrylamide gels. No statistically
      significant differences were observed in allelic and genotypic frequencies
      between SLE and healthy subjects (Fisher exact test). Nevertheless, the 2677A
      allelic frequency was lower in SLE patients with malar rash (0.007) compared with
      patients without this feature (0.04; P = 0.0054), while the frequency of this
      variant was higher in SLE patients with pleuritis (0.07) compared with patients
      without this feature (0.01; P = 0.0156). We suggest that although the ABCB1
      polymorphisms do not directly interfere in SLE susceptibility, their evaluation,
      especially the 2677A allele, in other immunological processes may be interesting
      since they can interfere in clinical features of this disease.

PMID- 18820767
TI  - Humoral and cellular immune responses to Blomia tropicalis and concanavalin A
      binding fractions in atopic patients.
AB  - Blomia tropicalis, Dermatophagoides pteronyssinus and D. farinae are prevalent
      house dust mites. Concanavalin A-binding components derived from B. tropicalis
      (Bt-ConA extract) are highly immunogenic in allergic diseases. The aim of the
      present study was to evaluate the humoral and cellular immune responses to B.
      tropicalis in mite-sensitized patients. A total of 137 patients with allergic
      rhinitis with/without asthma and 109 non-atopic subjects were selected and
      analyzed by the skin prick test, and for total serum IgE and specific IgE levels
      to both Bt-total and Bt-ConA extracts, their proliferative response and cytokine
      (IFN-gamma and IL-5) production by peripheral blood mononuclear cells (PBMC)
      stimulated with both extracts. Skin prick test showed that 70% of the patients
      were sensitized to Bt (Bt+) and similar levels of specific IgE to Bt-total and Bt
      ConA extracts were demonstrable in Bt+ patients. Significant PBMC proliferation
      was observed in response to Bt-total extract in Bt+, but not in Bt- patients and
      non-atopic subjects (P < 0.001). Bt-ConA extract induced increased proliferative
      responses in all patient groups compared to medium alone (P < 0.05), but these
      responses were significantly decreased in the presence of the mannopyranoside
      ConA inhibitor (P < 0.05). Significant IFN-gamma production was observed after Bt
      ConA stimulation of Bt+ patients (P < 0.05), while Bt-total extract had no
      effect. IL-5 production was consistently detected in Bt+ patients after allergen
      specific stimulation or with no stimulus, indicating that PBMC from allergic
      patients are prone to produce Th2 profile cytokines, spontaneously or inductively
      by allergen restimulation. These data showed that ConA-binding components
      isolated from B. tropicalis may contain relevant antigens that are involved in
      both humoral and cellular immune responses. However, without an additional
      purification procedure to eliminate the residual contamination with ConA, its use
      in immunotherapeutic procedures cannot be recommended.

PMID- 18820768
TI  - Participation of the cholinergic system in the ethanol-induced suppression of
      paradoxical sleep in rats.
AB  - Sleep disturbance is among the many consequences of ethanol abuse in both humans
      and rodents. Ethanol consumption can reduce REM or paradoxical sleep (PS) in
      humans and rats, respectively. The first aim of this study was to develop an
      animal model of ethanol-induced PS suppression. This model administered
      intragastrically (by gavage) to male Wistar rats (3 months old, 200-250 g) 0.5 to
      3.5 g/kg ethanol. The 3.5 g/kg dose of ethanol suppressed the PS stage compared
      with the vehicle group (distilled water) during the first 2-h interval (0-2 h;
      1.3 vs 10.2; P < 0.001). The second aim of this study was to investigate the
      mechanisms by which ethanol suppresses PS. We examined the effects of cholinergic
      drug pretreatment. The cholinergic system was chosen because of the involvement
      of cholinergic neurotransmitters in regulating the sleep-wake cycle. A second set
      of animals was pretreated with 2.5, 5.0, and 10 mg/kg pilocarpine (cholinergic
      agonist) or atropine (cholinergic antagonist). These drugs were administered 1 h
      prior to ethanol (3.5 g/kg) or vehicle. Treatment with atropine prior to vehicle
      or ethanol produced a statistically significant decrease in PS, whereas
      pilocarpine had no effect on minutes of PS. Although the mechanism by which
      ethanol induces PS suppression is not fully understood, these data suggest that
      the cholinergic system is not the only system involved in this interaction.

PMID- 18820769
TI  - Lead reduces tension development and the myosin ATPase activity of the rat right
      ventricular myocardium.
AB  - Lead (Pb2+) poisoning causes hypertension, but little is known regarding its
      acute effects on cardiac contractility. To evaluate these effects, force was
      measured in right ventricular strips that were contracting isometrically in 45
      male Wistar rats (250-300 g) before and after the addition of increasing
      concentrations of lead acetate (3, 7, 10, 30, 70, 100, and 300 microM) to the
      bath. Changes in rate of stimulation (0.1-1.5 Hz), relative potentiation after
      pauses of 15, 30, and 60 s, effect of Ca2+ concentration (0.62, 1.25, and 2.5
      mM), and the effect of isoproterenol (20 ng/mL) were determined before and after
      the addition of 100 microM Pb2+. Effects on contractile proteins were evaluated
      after caffeine treatment using tetanic stimulation (10 Hz) and measuring the
      activity of the myosin ATPase. Pb2+ produced concentration-dependent force
      reduction, significant at concentrations greater than 30 microM. The force
      developed in response to increasing rates of stimulation became smaller at 0.5
      and 0.8 Hz. Relative potentiation increased after 100 microM Pb2+ treatment.
      Extracellular Ca2+ increment and isoproterenol administration increased force
      development but after 100 microM Pb2+ treatment the force was significantly
      reduced suggesting an effect of the metal on the sarcolemmal Ca2+ influx.
      Concentration of 100 microM Pb2+ also reduced the peak and plateau force of
      tetanic contractions and reduced the activity of the myosin ATPase. Results
      showed that acute Pb2+ administration, although not affecting the sarcoplasmic
      reticulum activity, produces a concentration-dependent negative inotropic effect
      and reduces myosin ATPase activity. Results suggest that acute lead
      administration reduced myocardial contractility by reducing sarcolemmal calcium
      influx and the myosin ATPase activity. These results also suggest that lead
      exposure is hazardous and has toxicological consequences affecting cardiac
      muscle.

PMID- 18820770
TI  - Trypanosoma cruzi infection induces up-regulation of cardiac muscarinic
      acetylcholine receptors in vivo and in vitro.
AB  - The pathogenesis of chagasic cardiomyopathy is not completely understood, but it
      has been correlated with parasympathetic denervation (neurogenic theory) and
      inflammatory activity (immunogenic theory) that could affect heart muscarinic
      acetylcholine receptor (mAChR) expression. In order to further understand whether
      neurogenic and/or immunogenic alterations are related to changes in mAChR
      expression, we studied two models of Trypanosoma cruzi infection: 1) in 3-week
      old male Sprague Dawley rats chronically infected with T. cruzi and 2) isolated
      primary cardiomyocytes co-cultured with T. cruzi and peripheral blood mononuclear
      cells (PBMC). Using [3H]-quinuclidinylbenzilate ([3H]-QNB) binding assays, we
      evaluated mAChR expression in homogenates from selected cardiac regions, PBMC,
      and cultured cardiomyocytes. We also determined in vitro protein expression and
      pro-inflammatory cytokine expression in serum and cell culture medium by ELISA.
      Our results showed that: 1) mAChR were significantly (P < 0.05) up-regulated in
      right ventricular myocardium (means +/- SEM; control: 58.69 +/- 5.54, N = 29;
      Chagas: 72.29 +/- 5.79 fmol/mg, N = 34) and PBMC (control: 12.88 +/- 2.45, N =
      18; Chagas: 20.22 +/- 1.82 fmol/mg, N = 19), as well as in cardiomyocyte
      transmembranes cultured with either PBMC/T. cruzi co-cultures (control: 24.33 +/-
      3.83; Chagas: 43.62 +/- 5.08 fmol/mg, N = 7 for both) or their conditioned medium
      (control: 37.84 +/- 3.84, N = 4; Chagas: 54.38 +/- 6.28 fmol/mg, N = 20); 2)
      [(3)H]-leucine uptake was increased in cardiomyocytes co-cultured with PBMC/T.
      cruzi-conditioned medium (Chagas: 21,030 +/- 2321; control 10,940 +/- 2385 dpm, N
      = 7 for both; P < 0.05); 3) plasma IL-6 was increased in chagasic rats, IL-1beta,
      was increased in both plasma of chagasic rats and in the culture medium, and TNF
      alpha level was decreased in the culture medium. In conclusion, our results
      suggest that cytokines are involved in the up-regulation of mAChR in chronic
      Chagas disease.

PMID- 18820771
TI  - Changes in types of muscle fibers induced by transcutaneous electrical
      stimulation of the diaphragm of rats.
AB  - The objective of the present study was to assess the effect of transcutaneous
      electrical diaphragmatic stimulation (TEDS) on different types of diaphragm
      muscle fibers. Male Wistar rats (8-12 weeks old) were divided into 2 experimental
      groups (N = 8 in each group): 1) control, 2) animals submitted to TEDS [frequency
      = 50 Hz; T(ON)/T(OFF) (contraction/relaxation time) = 2/2 s; pulse duration = 0.4
      ms, intensity = 5 mA with a 1 mA increase every 3 min for 20 min] for 7 days.
      After completing this treatment period, the I, IIA, IIB, and IID diaphragm muscle
      fibers were identified using the mATPase technique. Statistical analysis
      consisted of the normality, homoscedasticity and t-tests (P < 0.05). There was a
      19.6% (P < 0.05) reduction in the number of type I fibers and a 49.7% increase (P
      < 0.05) in type IID fibers in the TEDS group compared with the control group. An
      important result of the present study was that electrical stimulation with
      surface electrodes was efficient in altering the distribution of fibers in
      diaphragm muscle. This therapeutic resource could be used in the treatment of
      respiratory muscle alterations.

PMID- 18820772
TI  - Effect of exercise training and carvedilol treatment on cardiac function and
      structure in mice with sympathetic hyperactivity-induced heart failure.
AB  - The present investigation was undertaken to study the effect of beta-blockers and
      exercise training on cardiac structure and function, respectively, as well as
      overall functional capacity in a genetic model of sympathetic hyperactivity
      induced heart failure in mice (alpha(2A)/alpha(2C)ArKO). alpha(2A)/alpha(2C)ArKO
      and their wild-type controls were studied for 2 months, from 3 to 5 months of
      age. Mice were randomly assigned to control (N = 45), carvedilol-treated (N = 29)
      or exercise-trained (N = 33) groups. Eight weeks of carvedilol treatment (38
      mg/kg per day by gavage) or exercise training (swimming sessions of 60 min, 5
      days/week) were performed. Exercise capacity was estimated using a graded
      treadmill protocol and HR was measured by tail cuff. Fractional shortening was
      evaluated by echocardiography. Cardiac structure and gastrocnemius capillary
      density were evaluated by light microscopy. At 3 months of age, no significant
      difference in fractional shortening or exercise capacity was observed between
      wild-type and alpha(2A)/alpha(2C)ArKO mice. At 5 months of age, all
      alpha(2A)/alpha(2C)ArKO mice displayed exercise intolerance and baseline
      tachycardia associated with reduced fractional shortening and gastrocnemius
      capillary rarefaction. In addition, alpha(2A)/ alpha(2C)ArKO mice presented
      cardiac myocyte hypertrophy and ventricular fibrosis. Exercise training and
      carvedilol similarly improved fractional shortening in alpha(2A)/alpha(2C)ArKO
      mice. The effect of exercise training was mainly associated with improved
      exercise tolerance and increased gastrocnemius capillary density while beta
      blocker therapy reduced cardiac myocyte dimension and ventricular collagen to
      wild-type control levels. Taken together, these data provide direct evidence for
      the respective beneficial effects of exercise training and carvedilol in
      alpha(2A)/alpha(2C)ArKO mice preventing cardiac dysfunction. The different
      mechanisms associated with beneficial effects of exercise training and carvedilol
      suggest future studies associating both therapies.

PMID- 18820773
TI  - Histomorphometric analysis of the response of rat skeletal muscle to swimming,
      immobilization and rehabilitation.
AB  - The objective of the present study was to determine to what extent, if any,
      swimming training applied before immobilization in a cast interferes with the
      rehabilitation process in rat muscles. Female Wistar rats, mean weight 260.52 +/-
      16.26 g, were divided into 4 groups of 6 rats each: control, 6 weeks under
      baseline conditions; trained, swimming training for 6 weeks; trained-immobilized,
      swimming training for 6 weeks and then immobilized for 1 week; trained
      immobilized-rehabilitated, swimming training for 6 weeks, immobilized for 1 week
      and then remobilized with swimming for 2 weeks. The animals were then sacrificed
      and the soleus and tibialis anterior muscles were dissected, frozen in liquid
      nitrogen and processed histochemically (H&E and mATPase). Data were analyzed
      statistically by the mixed effects linear model (P < 0.05). Cytoarchitectural
      changes such as degenerative characteristics in the immobilized group and
      regenerative characteristics such as centralized nucleus, fiber size variation
      and cell fragmentation in the groups submitted to swimming were more significant
      in the soleus muscle. The diameters of the lesser soleus type 1 and type 2A
      fibers were significantly reduced in the trained-immobilized group compared to
      the trained group (P < 0.001). In the tibialis anterior, there was an increase in
      the number of type 2B fibers and a reduction in type 2A fibers when trained
      immobilized rats were compared to trained rats (P < 0.001). In trained
      immobilized-rehabilitated rats, there was a reduction in type 2B fibers and an
      increase in type 2A fibers compared to trained-immobilized rats (P < 0.009). We
      concluded that swimming training did not minimize the deleterious effects of
      immobilization on the muscles studied and that remobilization did not favor
      tissue re-adaptation.

PMID- 18820774
TI  - Training-related changes in the R-R interval at the onset of passive movements in
      humans.
AB  - The aim of the present study was to determine whether training-related
      alterations in muscle mechanoreflex activation affect cardiac vagal withdrawal at
      the onset of exercise. Eighteen male volunteers divided into 9 controls (26 +/-
      1.9 years) and 9 racket players (25 +/- 1.9 years) performed 10 s of voluntary
      and passive movement characterized by the wrist flexion of their dominant and non
      dominant limbs. The respiratory cycle was divided into four phases and the phase
      4 R-R interval was measured before and immediately following the initiation of
      either voluntary or passive movement. At the onset of voluntary exercise, the
      decrease in R-R interval was similar between dominant and non-dominant forearms
      in both controls (166 +/- 20 vs 180 +/- 34 ms, respectively; P > 0.05) and racket
      players (202 +/- 29 vs 201 +/- 31 ms, respectively; P > 0.05). Following passive
      movement, the non-dominant forearm of racket players elicited greater changes
      than the dominant forearm (129 +/- 30 vs 77 +/- 17 ms; P < 0.05), as well as both
      the dominant (54 +/- 20 ms; P < 0.05) and non-dominant (59 +/- 14 ms; P < 0.05)
      forearms of control subjects. In contrast, changes in R-R interval elicited by
      the racket players' dominant forearm were similar to that observed in the control
      group, indicating that changes in R-R interval at the onset of passive exercise
      were not attenuated in the dominant forearm of racket players. In summary,
      cardiac vagal withdrawal induced by muscle mechanoreflex stimulation is well
      maintained, despite long-term exposure to training.

PMID- 18820776
TI  - A fair homage.

PMID- 18820778
TI  - Heparin quality control in the Brazilian market: implications in the
      cardiovascular surgery.
AB  - INTRODUCTION: The change in the heparin solution trade mark in Brazil that had
      been commonly used in cardiac surgery has shown increased number in the
      coagulopathy, re-exploration and other side effects in our Institution and
      others. METHODS: All four different heparin solutions available in the Brazilian
      market were studied in the Connective Tissue Lab, HUCFF, UFRJ and compared to the
      Liquemine (out of the market) and the international control solution. All samples
      were evaluated by magnetic nuclear resonance as well as their anticoagulant
      effectiveness. RESULTS: There were significant differences among them regarding
      the anticoagulant activity. It was also observed contamination with other
      dermatan sulfate, samples chemically degraded and with significant change in the
      molecular weight. CONCLUSION: Among the studied samples, none of them can offer
      security in cardiac surgeries on pump. None of them has demonstrated similar
      quality to Liquemine, which is not available in the Brazilian market.

PMID- 18820779
TI  - The use of ultrafiltration for inflammatory mediators removal during
      cardiopulmonary bypass in coronary artery bypass graf surgery.
AB  - OBJECTIVE: To investigate the effectiveness of ultrafiltration in removing
      inflammatory mediators released by cardiopulmonary bypass and to correlate
      ultrafiltration with alterations in organic function according to the Sequential
      Organ Failure Assessment Score. METHODS: Forty patients were included and
      randomized into two groups: "no ultrafiltration" (n=20; Group I) and
      "ultrafiltration" (n=20; Group II). Activated complement 3 and 4, interleukins
      1beta, 6, 8 and tumor necrosis factor alfa were measured prior to anesthesia
      induction (Time 1), 5 minutes before cardiopulmonary bypass (Time 2), in the
      ultrafiltrated fluid (Time 3), 30 minutes (Time 4), and 6 (Time 5), 12 (Time 6),
      24 (Time 7), 36 (Time 8) and 48 (Time 9) hours following cardiopulmonary bypass.
      Sequential Organ Failure Assessment Score was evaluated at Time 1, 6 and 9.
      Statistical significance was established at p < 0.05. RESULTS: In the
      ultrafiltrated fluid, only tumor necrosis factor alfa levels were detected.
      Levels of activated complement 3 at Times 5 and 7 and activated complement 4 at
      Times 5 and 6 were significantly higher in the unfiltered Group, and levels of
      interleukin 6 were higher in the filtered Group at Times 7 and 8. Interleukins
      1beta, 8, tumor necrosis factor alfa, and the Sequential Organ Failure Assessment
      score were not significantly different between the groups. CONCLUSIONS:
      Ultrafiltration significantly filtered tumor necrosis factor alfa but did not
      influences serum levels of this cytokine. Ultrafiltration with the type of filter
      used in this study had no effect in organic dysfunction and should be used only
      for volemic control in patients undergo cardiopulmonary bypass.

PMID- 18820780
TI  - Standardization of video-assisted cardiac surgery technique: initial experience.
AB  - INTRODUCTION: Minimally invasive cardiac surgery has been performed in major
      worldwide centers, including procedure such as valves, coronary and congenital
      surgery. OBJECTIVE: To demonstrate our first works with noninvasive cardiac
      surgery by mean of the experience gained with general and thoracic surgery.
      METHODS: Whenever possible to carry out a minimally invasive cardiac surgery,
      this was the approach of choice. The left thoracoscopy was used in four cases:
      (1) symptomatic coronary-pulmonary fistula ligation; (2) implant of an epicardial
      electrode into the left ventricle for resynchronization; (3) excision of
      pericardial giant lipoma in the left atrium, and (4) resection of hemangiolipoma
      in the mediastinum. Right thoracoscopy with extracorporeal circulation through
      cardiopulmonary bypass via femoral vein and artery and cardiac arrest in
      ventricular fibrillation with moderate hypothermia were carried out in the
      following cases: (5) patient with mitral stenosis after surgical repair with
      Carpentier ring 12 years before. An anterior and posterior commissurotomy without
      thoracotomy was successfully made; (6) patient with idiopathic dilated
      cardiomyopathy, high-response atrial fibrillation, and severe mitral
      insufficiency, underwent mitral repair surgery with Gregori's ring and ablation
      of the pulmonary veins with radio-frequency catheter. (MAZZE modified). RESULT:
      No death occurred in this series and the surgical result in all cases was highly
      satisfactory. All patients were discharged from hospital with a mean time of 5.5
      +/- 5 days after intervention. CONCLUSION: Our initial experience in this field
      proves the effectiveness and the viability in introducing this type of technique.

PMID- 18820781
TI  - High-frequency ultrasonic waves cause endothelial dysfunction on canine
      epicardial coronary arteries.
AB  - OBJECTIVE: Application of ultrasound energy by an endarterectomy probe can
      facilitate the removal of atheromatous plaque, but the effect of this procedure
      on surrounding vessel structure and function is still a matter of experimental
      investigations. METHODS: To determine whether ultrasound energy impairs the
      production of nitric oxide or damages vascular smooth muscle function, isolated
      canine epicardial coronary artery segments were exposed to either high (25 W) or
      low (0-10 W) ultrasonic energy outputs, for 15 seconds, using an endarterectomy
      device prototype. After exposure, segments of epicardial coronary artery were
      studied in organ chambers. The following drugs were used: adenosine diphosphate
      (ADP), acetylcholine (Ach) and sodium fluoride (NaF) to study endothelium
      dependent relaxation and sodium nitroprusside (SNP) and isoproterenol to evaluate
      endothelium-independent relaxation. RESULTS: Application of high ultrasonic
      energy power impaired endothelium-dependent relaxation to ADP (10(-9)-10(-4) M),
      Ach (10(-9)-10(-4) M) and NaF (0.5-9.5 mM) in epicardial coronary arteries.
      However, low ultrasound energy output at the tip of the probe did not alter the
      endothelium-dependent relaxation (either maximal relaxation or EC50) to the same
      agonists. Vascular smooth muscle relaxation to isoproterenol (10(-9)-10(-5) M) or
      SNP (10(-9)-10(-6) M) was unaltered following exposure to either low or high
      ultrasonic energy outputs. CONCLUSION: These experiments currently prove that
      ultrasonic energy changes endothelial function of epicardial coronary arteries at
      high power. However, ultrasound does not alter the ability of vascular smooth
      muscle of canine epicardial coronary arteries to relax.

PMID- 18820782
TI  - The use and midium-term evaluation of decellularized allograft cusp in the
      surgical treatment of the tetralogy of fallot.
AB  - OBJECTIVE: To describe the technique of implantation and to show the
      echocardiographic follow-up of the decellularized cusps allografts used in
      patients with tetralogy of fallot. METHODS: Fifteen patients underwent this
      implantation between March 2005 and August 2007 and they were clinically followed
      up. An echocardiogram was performed to evaluate the morphofunctional result of
      the allografts. RESULTS: The mean follow-up was 12.7 months (1-25 months). The
      echocardiography results showed that pulmonary insufficiency was mild in nine
      (60%) patients, moderate in three (20%) patients, and severe in three (20%)
      patients. The results also showed that the systolic right ventricle function was
      normal in 13 (86.7%) and that there was mild dysfunction in two (13.3%). Eleven
      (73.4%) patients did not present any gradient in the right ventricular outflow
      tract and four (26.6%) presented mild stenosis. The mobility of the cusps were
      normal in all cases and there was no thickness larger than 1.5 mm. There was no
      calcification; 14 patients (93.3%) presented Z score between -1 and 0,7 and one
      patient presented dilated pulmonary annulus with a Z score of + 2.5. CONCLUSION:
      In midium-term follow-up, the decellularized allograft seemed to be a good option
      for right ventricle outflow tract enlargement in patients underwent tetralogy of
      Fallot.

PMID- 18820783
TI  - Effect of ventral cardiac denervation in the incidence of atrial fibrillation
      after coronary artery bypass graft surgery.
AB  - OBJECTIVE: To evaluate the effect of ventral cardiac denervation in the incidence
      of atrial fibrillation after coronary artery bypass surgery. METHODS: Between
      September and November, 50 patients without history or previous diagnosis of
      atrial arrhythmia from the same institution presenting coronary heart disease
      with indication for coronary artery graft bypass surgery were enrolled in a
      prospective and randomized study. The exclusion criteria were: patients older
      than 75 years of age, previous history of atrial arrhythmia and associated heart
      surgeries. Denervation was performed before cardiopulmonary bypass and it was
      achieved by removing the adipose tissues around the superior vena cava, aorta and
      pulmonary artery. The groups were compared regarding demographic, clinical and
      operative variables. RESULTS: There were no hospital mortalities. The additional
      time for the denervation was 7.64+/-2.33 minutes, and there were no associated
      complications. Postoperative atrial fibrillation was present in two (8%) patients
      of the Control Group and in three (12%) patients who underwent ventral cardiac
      denervation. The risk of postoperative atrial fibrillation in patients undergoing
      ventral cardiac denervation was 22% higher than in the Control Group (0.56
      2.66,confidence interval); however, this outcome was not statistically
      significant (p=0.64). CONCLUSION: Ventral cardiac denervation, despite being a
      fast and low-risk procedure, does not significantly reduce the incidence of
      atrial fibrillation after coronary artery bypass graft surgery.

PMID- 18820784
TI  - CPAP at 10 cm H2O during cardiopulmonary bypass does not improve postoperative
      gas exchange.
AB  - OBJECTIVE: To compare postoperative (PO) pulmonary gas exchange indexes in
      patients submitted to myocardial revascularization (MR) with or without the
      application of continuous positive airway pressure (CPAP) during cardiopulmonary
      bypass (CPB). METHODS: Thirty adult patients submitted to MR with CPB between
      March and September 2005 were randomly allocated to two groups: CPAP (n=15),
      patients that received CPAP at 10 cm H2O during CPB, and control (n=15), patients
      that didn't receive CPAP. PaO(2)/FiO2 and P(A-a)O2 were analyzed at four moments:
      Pre (just before CPB, with FiO2=1.0 ); Post (30 min post-CPB, with FiO2=1.0);
      immediate PO period (12h post-surgery, with FiO2=0.4 by using a Venturi(R) facial
      mask) and first PO day (24h post-surgery, with FiO2=0.5 by a facial mask).
      RESULTS: PaO2/FiO2 and P(A-a)O2 tend to get significantly worst as time elapsed
      during the postoperative period in both groups, but no differences were observed
      between them at any moment. When PaO2/FiO2 was subdivided into three categories,
      a greater prevalence of patients with values between 200 mmHg and 300 mmHg were
      observed in CPAP group only at moment Post (30 min post-CPB; p = 0.02).
      CONCLUSION: CPAP at 10 cm H2O administered during CPB, although had lightly
      improved PaO2/FiO2 at 30 minutes post-CPB, had no significant sustained effect on
      postoperative pulmonary gas exchange. We concluded that in patients submitted to
      MR, application of 10 cmH2O CPAP does not improve postoperative pulmonary gas
      exchange.

PMID- 18820785
TI  - Intracardiac correction of tetralogy of fallot in the first year of life: short
      term and mid-term results.
AB  - OBJECTIVE: To evaluate short-term and medium-term results of intracardiac
      correction of tetralogy of fallot in the first year of life. METHODS: From
      January 1996 to October 2004, 67 consecutive infants ranging in age from 1 to 11
      months (mean: 7.2 months) and weighing from 4 to 10 kilograms (mean: 7.1
      kilograms) underwent elective total correction of tetralogy of fallot. The
      surgery was accomplished with conventional cardiopulmonary bypass and moderate
      hypothermia. Right ventriculotomy was performed in 60 (89.5%) cases and an
      atriopulmonary approach was used in the other seven (10.5%) cases. RESULTS:
      Cardiopulmonary bypass time ranged from 35 to 147 minutes (mean: 78.8 +/- 21
      minutes), and aortic clamping time ranged from 25 to 86 minutes (mean: 51.8 +/-
      15.6 minutes). Transannular enlargement of the right ventricular outflow tract
      was needed in 50 (64.1%) patients. Gradient between the right ventricle and
      pulmonary artery after correction varied from 0 to 54 mmHg (mean: 15.5 +/- 10.8
      mmHg). There were two (2.98%) early deaths. Follow-up of the 65 survivors ranged
      from 7 to 115 months (mean:44.0 +/- 35 months). There was one late noncardiac
      death. All other patients are asymptomatic. The actuarial survival curve at 12
      years, including operative mortality, was 97%. Ten patients were evaluated by
      magnetic nuclear angioresonance. CONCLUSIONS: Intracardiac correction of
      tetralogy of fallot in the first year of life may be performed with low morbidity
      and mortality and good late results.

PMID- 18820786
TI  - Trimetazidine as cardioplegia addictive without pre-treatment does not improve
      myocardial protection: study in a swine working heart model.
AB  - OBJECTIVE: The aim of this study is to verify in an isolated working heart swine
      model if the acute administration of trimetazidine to cardioplegia, without pre
      treatment improves heart performance. METHODS: Eighteen pairs of swine were used
      in this working heart model, divided into three groups (n = 6) that underwent
      regional and global ischemia. Each group was selected to a different treatment:
      St. Thomas cardioplegia (ST), St. Thomas enriched with trimetazidine (TMZ) and
      control group (Co). Data was collected during reperfusion period at 30, 60 and 90
      minutes. Hemodynamic parameters such as elastance contractility index (Emax),
      preload recruitable stroke work relationship (PRSW) and heart "stiffness" (EDPVR)
      were measured. Other data included coronary flow, lactate, oxygen and glucose
      consumption. Results were statistically analyzed. RESULTS: All contractility data
      were not significantly different among three groups. Lactate became constantly
      higher according to time uniformly in all three groups. Coronary flow, glucose
      consumption and oxygen consumption presented large variations during time periods
      but according to treatments showed no statistical differences in all three
      groups. Left ventricle final weight was significantly lower in trimetazidine
      group compared to both other groups. CONCLUSION: Administration of trimetazidine
      enhanced cardioplegia, without pre-treatment, showed no hemodynamic or metabolic
      improvement in swine isolated working heart model.

PMID- 18820787
TI  - Interatrial sulcus opening during multiple grafts harvesting for heart and lung
      transplantation: anatomical study.
AB  - OBJECTIVE: To evaluate the impact of the interatrial sulcus opening regarding of
      left atrium gain when harvesting heart and lungs for transplantation. METHODS: It
      was evaluated the left atrium dimension, from the right mediastinal side, after
      the interatrial sulcus dissection in fifty human cadaver. The interatrial sulcus
      gain was related with gender, age and ethnic group. RESULTS: The gain observed
      through right interatrial opening was, in media, 1.31 cm (0.3 cm to 2.5 cm). When
      that value was related to the variable gender it was observed that in the 27
      (54%) cases of the male the earnings was 1.19 cm +/- 0.6 cm and, in the 23 (46%)
      female, 1.21 cm +/- 0.5 cm (p = 0.895). In relation to age, it was observed that,
      in the 24 (48%) cases with smaller age than 50 years, the value was 1.08 cm +0.6
      cm and, in the 26 (52%) with larger age or same to 50 years, 1.36 cm +/- 0.6 cm
      (p = 0.088). In relation to ethnic group, it was observed that the value of the
      earnings in the 31 (62%) cases of whites it was 1.34 cm +/- 0.5 cm and, in the 19
      (38%) non white, 1.27 cm +/- 0.4 cm (p = 0.589). CONCLUSION: Heart grafts and
      lung grafts must be harvested maintaining adequate segments of left atrium near
      the heart and the pulmonary veins of the lungs that will be transplanted.
      Although there is no correlation between the observed gain in the interatrial
      sulcus dissection and the variables gender, age and ethnic group, our results
      confirm that the interatrial sulcus opening can give access to significant
      extension of left atrium wall when separating heart and lungs.

PMID- 18820788
TI  - Hybrid CABG: an alternative for perfusion time decrease.
AB  - OBJECTIVE: To evaluate the decrease of CPB time and its related complications in
      CABG using a hybrid alternative method. METHODS: Ninety patients were
      retrospectively analyzed between March 2000 and August 2006. All were treated
      with three or more grafts and divided into two groups: Group 1 was the hybrid
      group--45 patients who had been operated by the hybrid technique; Group 2 was the
      total group--45 patients operated in on-pump. RESULTS: In the hybrid group, the
      CPB time varied from 20 min. to 81 min. In the total group, the CPB time varied
      from 60 min. to 210 min. (p<0.001). The aorta cross-clamping time varied in the
      first group from 7 min. to 70 min. In Group 2, from 34 to 100 min. (p<0.001). A
      statistically significant difference was found between these two groups in
      relation to the occurrence of postoperative atrium fibrillation and renal
      dysfunction. CONCLUSION: Using the hybrid technique it is possible to reduce the
      CPB time, as well as the occurrence of some postoperative complications.
      Probably, this decreasing in atrial fibrillation and renal dysfunction incidences
      could be explained due to a less significant inflammatory activation, which is a
      consequence of a shorter CPB time.

PMID- 18820789
TI  - Postoperative cognitive dysfunction after cardiac surgery.
AB  - Postoperative cognitive dysfunction is frequent in cardiac surgeries leading to
      major consequences. The physiopathological processes involved in this condition
      are still not completely elucidated, despite the multifactor character. Besides
      pre-operative factors such as age and education, some intra-operative factors are
      also of extreme importance. However, according to a vast literature on the
      subject, these factors are not capable to clarify the totality of the cases,
      taking us to a genetic base for this neurological sequel. In this revision, we
      briefly assess the factors involved in this cognitive dysfunction as well as
      discuss the pharmacotherapy in the prevention of this event.

PMID- 18820790
TI  - Bentall and De Bono surgery for correction of valve and ascending aortic disease:
      long-term results.
AB  - OBJECTIVE: A retrospective study was performed in a series of consecutive
      patients who underwent a Bentall and De Bono procedure. METHODS: Data were
      removed of medical records and follow-up data were obtained from clinical records
      and direct contact with patients. A total of 39 patients were studied between
      January 1996 and December 2005. RESULTS: The median age was 47 years (range 14
      70). There were 33 males and six females. Eleven (25.5%) patients presented
      Marfan syndrome and one (2.5%) Turner syndrome. Nineteen (48.5%) patients had
      hypertension, eight (20.5%) had history of smoking, six (15.5%) had history of
      alcoholism, eight (20.5%) had dyslipidemia, two (5.0%) had diabetes and one
      (2.56%) had myocardial infarct previously. Twenty-eight (72%) patients were in II
      III NYHA class in the moment of the surgery. Annulo-aortic ecstasy was present in
      14 (35.9%) patients and aortic aneurysms in 16 (41%). The median time in
      intensive care unit was 8.79 days with range 2-23 days. Four (10.0%) patients
      underwent an emergency operation and 35 (90%) elective. The overall hospital
      mortality was 5% (2/39). The event-free survival is 94.87% at 1 year and 84.61%
      at in 5 and 10. The median time of follow-up was 46.5 months (range 14-120
      months). CONCLUSION: The Bentall and De Bono technique obtained excellent results
      in the short-term and long-term, which support the continued use of the
      compositive graft technique as the preferred method of treatment for patients
      with aortic root disease. Our findings confirm the current literature data.

PMID- 18820791
TI  - EuroSCORE and the patients undergoing coronary bypass surgery at Santa Casa de
      Sao Paulo.
AB  - OBJECTIVE: The aim of this study was to assess the performance of the European
      Risk System in Cardiac Operations (EuroSCORE) model to predict mortality in
      patients undergoing myocardial revascularization at the Division of
      Cardiovascular Surgery of Santa Casa de Sao Paulo Medical School. METHODS: From
      May 2005 to November 2006, 100 consecutive patients undergoing coronary artery
      bypass surgery were retrospectively analyzed. The records of these patients were
      reviewed in order to retrieve those variables included in the EuroSCORE risk
      scoring method. The correlation of predicted and observed mortality was compared.
      Statistical analysis was performed using chi-square test for univariate analysis
      and Hosmer-Lemeshow Test for logistic regression model. RESULTS: Hospital
      mortality was 5%. For EuroSCORE univariate analysis, findings were as follows:
      score 0-2 predicted mortality 0.40%, observed 0.00%; score 3-5 predicted
      mortality 1.45%, observed 0.00%; score greater than 6 predicted mortality 3.15%,
      observed 7.94%. Although these differences, p-value was 0.213 with no statistical
      significance. The p-value for the Hosmer-Lemeshow Test was < 0.001 indicating
      poor calibration of the model for this sample. CONCLUSION: The EuroSCORE model is
      a simple, objective system to estimate hospital mortality. However, to validate
      the logistic regression analysis, it is necessary hundreds of patients, which
      limit its widespread application.

PMID- 18820792
TI  - Operative treatment after iatrogenic left main dissection.
AB  - Coronary dissection has a significant morbidity and mortality. The ideal
      management of acute coronary occlusion is the prompt restoration of the vessel
      patency to limit the extent and duration of ischemia. In the setting of
      dissection during percutaneous procedure, the usual approach has been emergency
      aortocoronary bypass surgery. The authors present a case of a patient with left
      main dissection during percutaneous transluminal coronary angioplasty. This
      problem was successfully managed with emergent aortocoronary bypass surgery.

PMID- 18820793
TI  - Technical option on tetralogy of Fallot with abnormal coronary artery: cases
      report.
AB  - Report on two children, one 11 year-male and another one year-six-month-female
      with tetralogy of Fallot associated with anomalous origin of coronary artery
      crossing the right ventricle outlet tract. Diagnosis was done by echocardiography
      and cardiac catheterization. On surgical correction we used an external composite
      tubular pericardium bovine graft and posterior wall of the pulmonary artery
      between the right ventricle and the pulmonary artery trunk. Patients had an
      uneventful post-operative period and were discharged asymptomatic. It is more an
      option on correction of tetralogy of fallot with anomalous coronary artery.

PMID- 18820794
TI  - Giant myxoma in the left atrium: case report.
AB  - In this study is reported the case of a 63-year-old-woman with history of
      dyspnea, palpitations, and precordial pain who underwent cardiologic evaluation.
      The physical examination did not reveal abnormalities. The echocardiogram showed
      great mass in the left atrium, suggesting myxoma which was confirmed by
      tomography and catheterization. The patient underwent surgical treatment with a
      good postoperative evolution. The diagnosis of myxoma was confirmed by
      histopathologic study. In this study is included a bibliographic review and a
      comment emphasizing the diagnostic difficulty based on signs and symptoms, as
      well as the details about the development of bilateral pleural effusion possibly
      related to the myxoma.

PMID- 18820795
TI  - Parasternal approach for redo in ascending aorta pseudoaneurysm.
AB  - Aortic ascending pseudoaneurysm is a rare complication following aortic root
      surgery. The surgical solution of the complication is rather demanding and
      complex, especially when reaching the mediastinum. The latter translates into an
      elevated morbidity and mortality. We present a case performed through a minimal
      anterior right thoracotomy, which allowed us to dissect between the
      pseudoaneurysm and the internal site of the sternum as a first step prior to a
      second sternotomy. By using this approach, we minimized bleeding risks and the
      possibility of aortic rupture. This technique could have the potential to be
      generally applicable in this complication after further evaluation.

PMID- 18820796
TI  - Cardiac surgery of emergency for resection of left atrial myxoma.
AB  - We report case of a female patient who during months presented pulmonary
      manifestation associated with nonspecific systemic symptoms resulting in several
      hospitalizations with the diagnostic hypothesis of pulmonary fibrosis. The
      echocardiographic study showed a great pedunculated left atrial myxoma prolapsing
      through the mitral valve for the left ventricle. In quite unfavorable clinical
      conditions the patient was sent to our Service for surgical treatment, evolving
      during the preparation for surgery with acute pulmonary edema and hemodynamic
      instability being submitted to a successfully surgery of emergency for resection
      of the tumor. The patient is asymptomatic.

PMID- 18820797
TI  - Surgical repair of rheumatic mitral valve disease with Gregori-Braile's ring.

PMID- 18820798
TI  - The use of decellularized homograft monocuspid in the treatment of truncus
      arterious by Barbero Marcial technique.

PMID- 18820799
TI  - Re: Comments to the study "Cell therapy plus transmyocardial laser
      revascularization: a proposed alternative procedure for refractory angina".

PMID- 18820800
TI  - The informed consent.

PMID- 18820801
TI  - [ABE&M and impact factor. ].

PMID- 18820802
TI  - [Adipose tissue: a brief historical perspective and the present moment. ].

PMID- 18820803
TI  - [The hypothesis of common pole between pre-eclampsia and gestational diabetes].

PMID- 18820804
TI  - [Assessment instruments for a Health-Related Quality of Life in diabetes
      mellitus].
AB  - The assessment of Health-Related Quality of Life (HRQoL) has been increasingly
      used to measure the overall impact of diseases in people's life. Diabetes
      mellitus (DM) is a chronic disease associated with high morbidity, mortality, and
      HRQoL impairment in patients. In longitudinal studies, the psychosocial impact of
      DM predicts mortality. The objective of this review is to describe and to analyze
      the main instruments used for the HRQoL evaluation in patients with DM. Generic
      instruments such, as the Quality of Well-Being Scale (QWB), Medical Outcomes
      Study 36-item Short-Form Health Survey (SF-36), EuroQol (EQ-5D) and specific
      instruments as the Diabetes Care Profile (DCP), Diabetes Quality of Life Measure
      (DQOL), Diabetes Impact Measurement Scales (DIMS), Appraisal of Diabetes Scale
      (ADS), Audit of Diabetes-Dependent Quality of Life (ADDQoL), Diabetes Health
      Profile (DHP-1 and DHP-18), Questionnaire on Stress in Patients with Diabetes
      Revised (QSD-R), Well-Being Enquiry goes Diabetics (WED), Diabetes-Specific
      Quality-of-life Scale (DSQOLS), Diabetes 39 (D-39) Problems Areas in Diabetes
      (PAID) were analyzed. PAID is the only translated and validated instrument
      available in Brazil. The generic and specific instruments have their stregths and
      shortcomings for evaluation of HRQL in patients with DM. The combined use of both
      generic (such as the SF-36) and specific (such as the PAID) appears to be a
      consistent way to evaluate HRQoL as a construct in Brazilian patients with DM.
      The present article reviews a variety of instruments and emphasizes the urgent
      need for validation studies of such instruments to be used in Brazilian subjects
      with DM.

PMID- 18820805
TI  - [The role of advanced glycation end-products (AGEs) in the development of
      vascular diabetic complications].
AB  - The advanced glycation end-products (AGEs) constitute a class of heterogeneous
      molecules formed by amino-carbonyl reactions of a non-enzymatic nature, which
      occur at an accelerated rate in the hyperglycemic state of diabetes. Considered
      important pathogenic mediators of diabetic complications, AGEs are capable of
      irreversibly modifying the chemical properties and functions of diverse
      biological structures. In this review, recent data from literature is presented
      describing the pathways of AGEs formation, their metabolism, the main mechanisms
      of action of these substances in the triggering of pathological processes
      associated with diabetes, as well as methods of AGEs determination in biological
      samples. This text also points to new perspectives in anti-AGE therapies, an
      example of which is the studies involved with the action of natural compounds of
      food, which can represent a potential coadjuvant therapy for people with diabetes
      or other pathologies associated with the degenerative accumulation of AGEs.

PMID- 18820806
TI  - [Role of diet on chronic inflammation prevention and control - current
      evidences].
AB  - It is known that low chronic inflammation occurs in several stages of non
      transmissible chronic diseases, including cardiovascular diseases, obesity and
      diabetes mellitus, among others. Observational studies and clinical trials
      indicate that diet plays an important role in the reduction of such diseases. The
      present manuscript discusses the studies that linked diet macronutrient
      composition and the levels of inflammatory markers. It has been suggested that
      the consumption of high glycemic index diets, which have low fiber content and
      are rich in trans fat cause the activation of the immune system, leading to
      excessive production of pro-inflammatory mediators and the reduction of the anti
      inflammatory ones. Although the results are controversial, healthy dietary
      intakes with the reduction in fat intake (especially trans and saturated fat) and
      the increase in fruits, vegetables, and whole grain consumption seem to be
      associated with the improvement in subclinical inflammatory condition.

PMID- 18820808
TI  - Gestational diabetes and pre-eclampsia: common antecedents?
AB  - OBJECTIVE: To evaluate commonality of risk factor profiles of women who develop
      gestational diabetes and pre-eclampsia. METHODS: Prospective cohort study in
      prenatal clinics of the Brazilian Unified Health System in six state capitals.
      4.766 pregnant women between 20 to 48 years old were consecutively enrolled
      between 20th and 28th gestational weeks. Smoking habits and traditional risk
      factors for pre-eclampsia and gestational diabetes were obtained by the interview
      at enrollment. Gestational diabetes was diagnosed using a 75-g oral glucose
      tolerance test and pre-eclampsia through chart review. RESULTS: Both gestational
      diabetes and pre-eclampsia were associated with age (OR 2.07; 95% CI 1.65-2.23
      and OR 1.55; 95% CI 1.08-2.23, respectively), pre-pregnancy body mass index (OR
      1.62; 95% CI 1.40-3.53 and OR 1.83; 95% CI 1.52-4.80, respectively) and weight
      gain in early pregnancy (OR 1.28; 95% CI 1.12-1.47 and OR 1.27; 95% CI 1.06-1.52,
      respectively). Lower odds of gestational diabetes (OR 0.31; 95% CI 0.22-0.44) and
      pre-eclampsia (OR 0.36; 95% CI 0.20-0.51) were observed in nulliparous women who
      have smoked during pregnancy. CONCLUSIONS: Gestational diabetes and pre-eclampsia
      share a pattern of risk factors, suggesting the possibility of common aetiology.

PMID- 18820807
TI  - A hypercaloric pellet-diet cycle induces obesity and co-morbidities in Wistar
      rats.
AB  - The present study was carried to develop and analyze the consequences of
      hypercaloric pellet-diet cycle that promotes obesity in rats. Male Wistar rats
      were randomly distributed into two groups that received either normal diet (ND; n
      =32; 3,5 Kcal/g) or a hypercaloric diet (HD; n =32; 4,6 Kcal/g). The ND group
      received commercial Labina rat feeding while the HD animals received a cycle of
      five hypercaloric diets over a 14-week period. The effects of the diets were
      analyzed in terms of body weight, body composition, hormone-metabolite levels,
      systolic arterial pressure and glucose tolerance at the 5% significance level.
      The hypercaloric pellet diet cycle promoted an increase in body weight and fat,
      systolic arterial pressure and a high serum level of glucose, triacylglycerol,
      insulin and leptin. The HD group also presented an impaired glucose tolerance. In
      conclusion, the results of this study show that the hypercaloric pellet-diet
      cycle promoted obesity in Wistar rats and displayed several characteristics that
      are commonly associated with human obesity, such as high arterial pressure,
      insulin resistance, hyperglycaemia, hyperinsulinaemia, hyperleptinaemia and
      dyslipidaemia.

PMID- 18820809
TI  - [Prevalence of thyroid dysfunction and antithyroid antibodies in type 1 diabetic
      mellitus patients and their first degree relatives].
AB  - Diabetes Mellius Type 1 (DM1) is frequently associated to Autoimmune Thyroid
      Disease (AITD). The prevalence of AITD among diabetic patients varies between 3
      to 50% and the incidence is also big among their family members, when compared to
      the population in general. OBJECTIVES: To investigate the prevalence of AITD in
      patients with DM1; to evaluate possible differences concerning the clinical
      evolutive behavior of DM1 among diabetic patients with or without AITD and to
      study the prevalence of AITD among the diabetes patients' relatives. MATERIALS
      AND METHODS: 124 prontuaries of diabetic patients (type 1) were revised and data
      was gathered concerning the thyroid function and the anti-thyroid antibodies.
      Patients with and without AITD were compared in relation to the level of
      glycosylated hemoglobin, the presence of acute and chronic complications, the age
      of the patient at the time of the diagnosis, time of evolution of the disease,
      daily dose of insulin and other factors. A control case study was conducted with
      54 first degree relatives of the diabetic patients who took part in the study;
      the thyroid function as well as the presence of anti-thyroid antibodies were
      evaluated in 32 of those first degree relatives with AITD, and in 22 of those
      without AITD. RESULTS: The prevalence of AITD and of hormonal dysfunction among
      diabetic patients was 35.5% and 19.3%, respectively. No significant differences
      were found between groups in respect to clinical outcome or to diabetic chronic
      complications. However, prevalence of AITD and hormonal dysfunction were found to
      be higher among first degree relatives of diabetic patients with AITD than among
      relatives of diabetic patients without AITD. CONCLUSIONS: The prevalence of
      autoimmune thyroid disease in diabetic patients and in their first degree
      relatives is high. Thyroid function screening is therefore justified in these
      cases, especially in first degree relatives of diabetics with autoimmune thyroid
      disease.

PMID- 18820810
TI  - [Is silent hypoglycemia part of ideal glycemic control in DM1 patients? -
      hypoglycemic state by CGMS vs. glycemic average].
AB  - BACKGROUND: To evaluate the impact of silent hypoglycemic state in glycemic
      control in type 1 diabetic patients (DM1) by CGMS. METHODS: 87 DM1 patients
      (45%M/55%F) submitted to a 72 h CGMS profile were classified in 4 groups. It was
      analyzed: unrecognized hypoglycemia (<70 mg/dL); duration time of silent
      hypoglycemia in which patients were classified into G1 (<5%), G2 (5-10%), G3 (10
      20%) and G4 (>20%) of hypoglycemic state by CGMS; A1c and mean capillary glucose
      (MCG) in each group. RESULTS: The silent hypoglycemia was detected in 64.5% of
      patients and nighttime episodes of hypoglycemia lasted longer (min) than daytime
      episodes in all groups (p<0.001). It was verified 41.4% of patients under than 5%
      of time in hypoglycemic state, 21.8% between 5-10%, 23% between 10-20% and 13.8%
      with more than 20% of CGMS in silent hypoglycemia. This data showed significant
      decreased in MCG when the duration time of silent hypoglycemia was longer
      (p=0.006). CONCLUSION: The silent hypoglycemia is common in DM1 patients and most
      frequently in night time period. To take an average glycemia of 120-160 mg/dL in
      these patients, it was necessary a 10-20% of CGMS period in silent hypoglycemia
      in these patients.

PMID- 18820811
TI  - [Association among weight loss, bone mass, body composition and dietary intake of
      post-pubertal obese adolescents].
AB  - OBJECTIVE: To verify the effects of weight loss on bone mass of obese adolescents
      submitted to a nutritional intervention based on a hypocaloric diet and
      nutritional advice over a nine-month-period. METHODS: Anthropometry, body
      composition, BMD and dietary intake were evaluated. RESULTS: Fifty-five
      adolescents, 78.2% females, within an average age of 16.6 (1.4) years old
      participated in the study. Sixteen participants who completed the study did not
      lose weight. The group that adhered to the nutritional intervention had a mean
      weight loss of 6.2 (4.6)% baseline. There was a significant increase in total BMD
      and bone mineral content (BMC) in those adolescents who did not lose weight,
      while increased BMC and bone area were verified in participants who lost weight,
      mainly when associated with body composition alterations while changing weight.
      CONCLUSION: The increment in bone mineral density, even throughout weight loss,
      has showed no negative effect on bone mass and has also emphasized the importance
      of nutritional improvement in total bone mass during adolescence.

PMID- 18820812
TI  - [Body Mass Index, Waist Circumference and skinfolds for predicting lipid
      abnormalities in 11 years old children].
AB  - OBJECTIVE: To analyze the predictive capacity of Body Mass Index (BMI), Waist
      Circumference (WC) and Triceps Skin Folds (TSF) to diagnose of lipid
      abnormalities and to suggest cutoff points for these measures in order to
      identify this disease in children. METHODOLOGY: It was measured the BMI, WC, TSF
      and lipid profiles of 374 schoolchildren (11,25 +/- 0,28 years) from the public
      education system of Santa Maria, RS, Brazil. Area under the ROC curve (95%CI),
      sensitivity, specificity and predictive values were analyzed in order to identify
      the ideal cutoff points. RESULTS: The anthropometric variables only exhibited
      diagnostic capacity for TG among the girls and CT and LDL-C for the boys.
      CONCLUSIONS: It was concluded that a BMI of 19.3 kg/m(2) is a diagnostic value
      for abnormal TG levels in females and for abnormal CT and LDL-C among males.
      Elevated concentrations of CT and LDL-C can also be diagnosed in boys using cut
      off values of WC > 65.7 cm and TSF > 21.0mm.

PMID- 18820813
TI  - [Metabolic Syndrome in professional truck drivers who work on Highway BR-116
      within the area of Sao Paulo City - Regis Bittencourt].
AB  - The objective of this study was to determine the Metabolic Syndrome prevalence as
      well as identify variables related in truck drivers who work on Highway BR-116
      (Sao Paulo, Brazil). A total of 258 truck drivers were assessed and the variables
      studied were: body mass index, waist circumference, blood pressure,
      triglycerides, total and fraction cholesterol, glycemia and C reactive protein.
      Cardiovascular disease risk was evaluated by Framingham's risk score whereas the
      Metabolic Syndrome based on the First Brazilian Guideline for Diagnosis and
      Treatment of the Metabolic Syndrome. The significance level adopted was p< 0.05
      and univariate and multivariate analysis were applied. The average age was of
      37.5+/-10.1. According to the anthropometric data, it was observed body mass
      index > or =25 kg/m(2) in 82%, waist circumference > or =94 cm in 58%, total
      cholesterol >240 mg/dL in 9%, LDL-c >160 mg/dL in 10%; HDL-c <40 mg/dL in 20%,
      triglycerides >200mg/dL in 22%, glycemia >110 mg/dL in 7%, and C reactive protein
      >0.5 mg/dL in 19%. Hypertension prevalence was 37%, 9% were identified at the
      highest/medium Framingham's risk score and 24% showed Metabolic Syndrome. The
      logistical regression analysis indicated independent association of the Metabolic
      Syndrome for the following variables (OD odds ratio, CI confidence interval at
      95%): body mass index (OR = 1.4007 CI 95% 1.192-1.661), use to check cholesterol
      (OR = 0.1020 CI 0.017-0.589) and Framingham's risk score (OR = 26.389 CI 2.520
      276.374). As a conclusion, it was observed a quite expressive prevalence of
      cardiovascular risk factors as well as Metabolic Syndrome in truck drivers.

PMID- 18820814
TI  - [Atherosclerotic risk factors associated with cardiorespiratory fitness and BMI
      in adolescents].
AB  - Previous research has demonstrated high prevalence of atherosclerotic risk
      factors in adolescents; however, the associate factors related to its onset are
      unclear. Therefore, the objective of this study was to relate inadequate blood
      pressure levels, total cholesterol (TC), HDL-C, LDL-C and triglycerides (TG) with
      different VO2max and BMI levels in a sample of 249 adolescents, aged between 12
      to 16 years old. For VO2max prediction, the 20 meters test was used. The BMI was
      calculated using the body mass/heigh(2) equation. The considerate inadequate
      levels were: blood pressure > or =90th percentile; total cholesterol > or =150
      mg/dL; LDL-C > or = 100 mg/dL, TG > or =100 mg/dL and HDL-C <45 mg/dL. Logistic
      regression was used as statistical procedures, with p<0.05. For the boys,
      significant associations were observed between the low VO2max with TC (OR 4.33;
      IC=1.23-15.20) and TG (OR=4.88; IC=1.15-20.79) and between overweight and TG
      (OR=4.33; IC=1.42-13.21). After BMI correction, the males subjects with low
      VO2max maintained their significant associations with TC (OR=5.73; IC=1.52-21.58)
      and TG (OR=3.81; IC=1.86-16.94). The evidences in this study suggested an inverse
      relationship of the cardiorespiratory fitness with TC and TG for boys,
      independently of the BMI.

PMID- 18820815
TI  - [Apoptosis, proliferation and spleen histomorphometry of adult female rats with
      thyroid and ovarian hypofunction].
AB  - Apoptosis, proliferation and histomorphometry of spleen were investigated in
      ovariectomized and non-ovariectomized adult Wistar rats maintained in
      hypothyroidism induced by daily administration of propylthiouracil (PTU) during
      120 days. Two groups ovariectomized euthyroid and non-ovariectomized euthyroid
      were used as controls. Plasma was collected for free T4 dosage and the spleen for
      histomorphometry analysis, apoptosis index and the immunohistochemistry
      expression of caspase 3 and CDC47. Values of free T4 were lower in rats treated
      with PTU (p<0.05). In the hypothyroid groups there was some decrease in the
      spleen weight as well as the number and size of lymphoid follicles and there was
      some increase in the apoptotic index and the caspase 3 expression (p<0.05).
      However, the increase in the apoptosis index and the expression of caspase 3 in
      ovariectomized hypothyroid rats spleen was less accentuated than non
      ovariectomized hypothyroid ones (p<0.05). The ovariectomized euthyroid group
      presented white pulp hyperplasia in comparison to the non-ovariectomized
      euthyroid group. There was no difference in the CDC47 expression between groups.
      It was concluded that the thyroid and ovarian hypofunction have distinct effects
      on the spleen and that in the hypothyroidism-hypogonadism association, the
      increase in the apoptosis index and in the expression of splenic caspase 3 is not
      as much as in isolated hypothyroidism.

PMID- 18820816
TI  - Incretin mimetics and dipeptidyl peptidase-4 inhibitors: innovative treatment
      therapies for type 2 diabetes.
AB  - The prevalence of diabetes and impaired glucose tolerance is predicted to
      dramatically increase over the next two decades. Clinical therapies for type 2
      diabetes mellitus (T2DM) have traditionally included lifestyle modification, oral
      anti-diabetic agents, and ultimately insulin initiation. In this report, we
      review the clinical trial results of two innovative T2DM treatment therapies that
      are based on the glucoregulatory effects of incretin hormones. Incretin mimetics
      are peptide drugs that mimic several of the actions of glucagon-like peptide-1
      (GLP-1) and have been shown to lower glycated hemoglobin (A1C) levels in patients
      with T2DM. Additionally, incretin mimetics lower postprandial and fasting
      glucose, suppress elevated glucagon release, and are associated with progressive
      weight reduction. Dipeptidyl peptidase-4 (DPP-4) inhibitors increase endogenous
      GLP-1 levels by inhibiting the enzymatic degradation of GLP-1. Clinical studies
      in patients with T2DM have shown that DPP-4 inhibitors reduce elevated A1C, lower
      postprandial and fasting glucose, suppress glucagon release, and are weight
      neutral. Collectively, these new drugs, given in combination with other
      antidiabetic agents, such as metformin, sulfonylureas, and/or thiazolidinediones,
      can help restore glucose homeostasis in poorly controlled patients with T2DM.

PMID- 18820817
TI  - [The importance of methodology in serum testosterone measurement: comparison
      between a direct immunoassay and a method based on high performance liquid
      chromatography and tandem mass spectrometry (HPLC/MS-MS)].
AB  - Serum testosterone in its total or free form, is a highly valuable diagnostic
      test and is available in the great majority of clinical laboratories. This
      reality was possible due to the development of simple and direct assays,
      adaptable to large automatic systems. Recent publications have called attention
      to the limitations of these simplified methodologies, mainly in samples with low
      concentration, as women and children. In this paper we present results obtained
      using a reference method based on high performance liquid chromatography and
      tandem mass spectrometry (HPLC/MS-MS) and its comparison with those obtained with
      a commercial routine immunoassay (electrochemiluminescent assay, ECLIA). Methods
      were compared in total testosterone measurement (n = 213), as well as in free
      testosterone evaluation based on calculation including sex hormone-binding
      protein (SHBG) levels (n = 135). Values obtained with ECLIA were significantly
      higher, with more marked dispersion in low concentration. This phenomenon is
      clearer when presented as a Bland-Altman plot. Difficulties in the implementation
      of reference methods as the one presented are discussed, as well as the necessity
      of caution in the interpretation of values obtained with routine assays, a matter
      of several publications in recent literature.

PMID- 18820818
TI  - [Short stature investigation: clinical, laboratorial and genetic aspects
      concerning the growth hormone insensitivity (GHI)].
AB  - It is reported in this study the clinical, laboratory and genetic aspects of
      short stature investigation with emphasis to the diagnostic approach of growth
      hormone insensitivity (GHI). This patient in case presented typical clinical
      features of GHI and his laboratory findings at prepubertal age were typical of
      those observed in GHI patients (low IGF-1 and IGFBP-3 levels, with high basal and
      stimulated GH levels). However, during the puberty, he presented normal IGFBP-3
      and IGF-1 levels that hindered the diagnosis. The molecular study disclosed a
      mutation in exon 7 of growth hormone receptor gene (S226I). The steps that
      demonstrated the causative effect of this mutation are shown here, and also a
      review of Brazilian GHI cases is given and new molecular defects in this field
      are discussed as well.

PMID- 18820819
TI  - Severe hypertension and hypokalemia as first clinical manifestations in ectopic
      Cushing's syndrome.
AB  - Ectopic ACTH production occurs in about 10% of all cases of Cushing's syndrome,
      and about 25% of cases of ACTH-dependent Cushing's syndrome. Diverse tumor types
      are able to produce ACTH ectopically, including small cell lung carcinoma.
      Ectopic ACTH secretion by malignant neoplasm has been reported to have earlier
      and more aggressive metabolic effects. We report a 59-year-old male patient with
      severe hypertension, metabolic alkalosis and hypokalemia as the first clinical
      manifestations of an ACTH-secreting small cell lung carcinoma, although the
      typical phenotypic features of Cushing's syndrome were not present. Ectopic
      Cushing's syndrome should always be ruled out in patients with severe
      hypertension and hypokalemia.

PMID- 18820820
TI  - Inequalities in health, social causation and the role of occupation.

PMID- 18820821
TI  - Inflammation but no DNA (deoxyribonucleic acid) damage in mice exposed to
      airborne dust from a biofuel plant.
AB  - OBJECTIVES: Particles in ambient air are associated with such health effects as
      lung diseases and cancer of the lung. Exposure to bioaerosols has been found to
      be associated with respiratory symptoms. The toxic properties of exposure to
      combustion and bioaerosol particles from biofuel plants have not been studied in
      detail. This study investigated whether exposure to dust from biofuel plants
      induces DNA (deoxyribonucleic acid) damage and inflammation in exposed mice.
      METHODS: DNA damage and inflammation were evaluated in mice exposed through the
      intratracheal installation of airborne dust collected at a biofuel plant at the
      straw storage hall and in the boiler room. The mice were given either a single
      dose of dust (18 or 54 microg) or four doses of 54 microg on each of four
      consecutive days. Control mice were exposed to a 0.9% sodium chloride solution.
      RESULTS: In the mice exposed to 4 x 54 microg of dust, the lung tissue mRNA
      (messenger ribonucleic acid) levels of interleukin-6 (IL-6), monocyte
      chemoattractant protein-1 (MCP-1), and macrophage inflammatory protein-2 (MIP-2)
      were increased more than 10-fold if the dust was from the boiler room and 30- to
      60-fold if the dust came from the straw storage hall. The levels of DNA strand
      breaks in broncheoalveolar lavage (BAL) cells from the mice exposed to dust did
      not differ from those in the control samples. CONCLUSIONS: The results indicate
      that the instillation of dust from a biofuel plant, at doses corresponding to 2
      weeks of exposure to human endotoxins, results in a strong inflammatory response
      without detectable DNA damage in BAL cells. The dust from the straw storage hall
      induced the strongest inflammatory response and had the highest concentration of
      most microbial components.

PMID- 18820822
TI  - Biochemical responses of cnidarian larvae to mercury and benzo(a)pyrene exposure.
AB  - The biochemical responses of planulae from the coral Porites astreoides exposed
      to 10 microg/L of benzo(a)pyrene (B(a)P) and to 10 microg/L of mercury (Hg) was
      evaluated. The survivorship of larvae only dropped significantly after 48 h of
      B(a)P exposure, whereas it remained at 98% for Hg exposure and up to 96 h.
      Exposure to B(a)P significantly increased free thiols, and the activity of
      glutathione-S-transferase and catalase were unaltered under exposure of any of
      the contaminants. This study is the first contribution of the biochemical effects
      in cnidarian larvae exposed to contaminants.

PMID- 18820823
TI  - General tissue characteristics of the lower urethral and vaginal walls in the
      domestic rabbit.
AB  - In European rabbits, the distal urethra (DU) opens into the anterior pelvic
      vagina forming a single canal by which females copulate, give birth, and urinate.
      We investigated whether the histological characteristics of the DU and the pelvic
      and perineal vagina are different. The DU and vagina of rabbits (Oryctolagus
      cuniculus) were cut and stained with hematoxylin-eosin and Masson's trichrome (n
      = 3). Data were compared by using Friedman's ANOVA for repeated measures. The
      walls of the DU and vagina are composed of mucosa, submucosa, smooth muscle, and
      an external layer. Differences in tissue characteristics of the mucosa,
      orientation of the smooth muscle fibers, components of the external layer
      (connective tissue, blood vessels, and striated musculature), and thickness of
      the tissue layers were found among regions. The lack of histological homogeneity
      along the urethra and vagina possibly reflects differences in the functions of
      each segment.

PMID- 18820824
TI  - Propylthiouracil, independent of its antithyroid effect, decreases VSMC collagen
      expression.
AB  - Propylthiouracil (PTU), in addition to its antithyroid effect, is recently found
      to have a potent antiatherosclerotic effect. Because collagen accumulation is the
      major contributor to the growth of atherosclerotic lesions and the neointimal
      formation after arterial injury, the aim of this study is to investigate the
      impact of PTU on collagen regulation. In the rat carotid injury model, PTU
      administration reversed the up-regulation of collagen in the neointima induced by
      balloon injury. In vitro, vascular smooth muscle cells (VSMCs), the main origin
      of arterial collagen, were treated with PTU. Propylthiouracil caused a
      concentration-dependent decrease in collagen I and III steady-state protein and
      mRNA levels, as determined by immuno-cytochemistry, Western, and/or Northern blot
      analyses. Transient transfection experiments using rat type I collagen promoter
      construct showed that PTU failed to affect collagen gene transcription in VSMCs.
      Actinomycin D studies demonstrated that the half-life of collagens mRNA decreased
      with PTU treatment, suggesting that PTU down-regulates collagen expression
      predominantly at the post-transcriptional level. Taken together, these data
      suggest that PTU inhibits VSMC collagen production via destabilization of
      collagen mRNA that contributes to its beneficial effect on atherogenesis and
      neointimal formation after arterial injury. However, whether the destabilization
      of collagen may induce plaque rupture in PTU-treated arteries merits further
      investigation.

PMID- 18820825
TI  - Pioglitazone reduces monocyte activation in type 2 diabetes.
AB  - Inflammation is involved in the pathophysiologic process of atherosclerosis, a
      frequent complication of type 2 diabetes. The purpose of our study was to
      investigate the effect of pioglitazone on systemic inflammatory markers and
      activation of circulating monocytes in type 2 diabetic patients through the
      dosage of IL-6. Twenty-four metformin-treated patients, in good glycemic control,
      were randomized to add pioglitazone for 8 weeks or to continue their previous
      treatment. Blood samples were collected before and at the end of the study to
      evaluate: serum levels of high sensitivity C-reactive protein (hs-CRP),
      interleukin (IL)-6 and leukocyte activation. IL-6 production of circulating
      monocytes after LPS stimulation was similar at baseline and showed a 54%
      reduction in pioglitazone-group at 8 weeks (9.1 pg/mL, range 0.0-24.3, P=0.04 vs.
      baseline) while, in controls, did not change at 8 weeks (16.9 pg/mL, range 1.5
      58.8). Treatment with pioglitazone, associated with metformin, showed a reduction
      of IL-6 monocyte production after their in vitro activation with LPS.

PMID- 18820826
TI  - The detection of sLFA-3 in plasma of patients with hemorrhagic fever with renal
      syndrome.
AB  - Hemorrhagic fever with renal syndrome (HFRS) is an acute viral disease
      characterized by endothelial dysfunction. The cellular immune response,
      especially the virus-specific CD8+ T lymphocytes, is known to attack vascular
      endothelial cells (VEC) and to contribute to the diffuse damage and penetrability
      increasing of VEC. Lymphocyte function associated antigen 3 (LFA-3) is expressed
      on T lymphocytes and VEC, which is contributed to the activation of T
      lymphocytes. The expression of LFA-3 on the activated T lymphocytes and VEC is
      highly increased, which can exfoliate into plasma to increase the level of
      soluble LFA-3 (sLFA-3) in plasma. So the change of sLFA-3 levels is correlated
      with the activation of T lymphocytes. In this study we detected the levels of
      sLFA-3 in plasma of patients with HFRS. We examined the levels of sLFA-3 in
      plasma samples collected from 53 HFRS patients by double antibody sandwich ELISA.
      We found variable, but persistently elevated levels of sLFA-3 throughout the
      various phases and types of the HFRS disease, which suggest that sLFA-3 levels
      have correlation with disease stages. Moreover, elevated sLFA-3 levels are
      closely correlated to the severity of HFRS and the degree of kidney damage.

PMID- 18820827
TI  - The analysis of CIS, SOCS1, SOSC2 and SOCS3 transcript levels in peripheral blood
      mononuclear cells of systemic lupus erythematosus and rheumatoid arthritis
      patients.
AB  - Being expressed in immune cells, cytokine-inducible SH2 protein (CIS) and
      suppressors of cytokine signaling proteins, SOCS1, SOCS2 and SOCS3, can regulate
      cytokine signaling and immune responses. To evaluate the possible expressional
      dysregulation of CIS, SOCS1, SOCS2 and SOCS3 in systemic lupus erythematosus
      (SLE) and rheumatoid arthritis (RA) patients, the transcript levels of these
      genes in peripheral blood mononuclear cells (PBMCs) from SLE and RA patients were
      determined and statistically compared with those in PBMCs from normal
      individuals. It was found that SLE patients with the active disease activity
      significantly express higher CIS transcript levels than normal individuals and
      SLE patients with the inactive disease activity, whereas the difference in SOCS1,
      SOCS2 and SOCS3 transcript levels between normal individuals and SLE patients is
      not statistically significant. However, transcript levels of these CIS/SOCS genes
      in RA patients were not significantly different from those in normal individuals,
      except that treatment with a TNF-alpha-blocking agent in RA patients appears to
      enhance the CIS transcript expression, but down-regulates the SOCS2 transcript
      expression in PBMCs. These data suggest that CIS can serve as an SLE disease
      marker and may be involved in the pathogenesis of SLE, and that TNF-alpha may
      play an important role in the regulation of CIS and SOCS2 gene expression in
      PBMCs in vivo.

PMID- 18820828
TI  - A black-streaked dwarf disease on rice in China is caused by a novel fijivirus.
AB  - An isolate of a plant reovirus causing severe stunting and dark leaf symptoms on
      rice from Guangdong, China, was similar in virion morphology and serologically
      related to rice black-streaked dwarf virus (RBSDV). The electrophoretic profiles
      of genome segments of the two viruses in agarose or polyacrylamide gel were
      indistinguishable. The four genome segments of the new isolate corresponding to
      RBSDV S7-S10 were amplified by ligation RT-PCR and sequenced. The size and
      organization of each genome segment was very similar to its counterparts in
      RBSDV, maize rough dwarf virus (MRDV), and mal de Rio Cuarto virus (MRCV).
      Sequence identity was greatest to RBSDV and MRDV (ranging from about 60-85%
      depending on the protein), but identities were always much lower than those
      between RBSDV and MRDV. These comparisons and phylogenetic analyses suggested
      that the virus represents a new species in genus Fijivirus group 2, tentatively
      named Rice black-streaked dwarf virus-2.

PMID- 18820829
TI  - A case of lymphangioleiomyomatosis with membranous nephropathy and likely
      systemic lupus.
AB  - Membranous glomerulonephritis is most often idiopathic, but it can be secondary
      to systemic lupus erythematosus, viral hepatitis, and drugs. A number of
      malignancies have also been associated with membranous glomerulonephritis,
      although a causal link has not been established yet. A young patient with
      lymphangioleiomyomatosis is described who developed massive proteinuria and was
      found to have membranous glomerulonephritis on renal biopsy. There were many
      pathological features and some clinical features that suggested the patient also
      suffered from systemic lupus erythematosus.

PMID- 18820830
TI  - Mental health and well being at work: the disposal workforce.

PMID- 18820831
TI  - Sustainable health for all by the year 2100?

PMID- 18820832
TI  - Communications about cervical cancer between women and gynecologists in Serbia.
AB  - OBJECTIVE: The age-standardized incidence rate of cervical cancer in Serbia is
      27.2 per 100,000 women, i. e., twice as high as in western European countries.
      This paper explores the communication which occurs between women and
      gynecologists in Serbia in relation to cervical cancer screening. METHODS: Our
      study was conducted in two phases: a qualitative phase (focus group discussions
      and in-depth interviews with women) and a quantitative phase (community-based
      survey). This paper reports the findings from both phases, and in particular, the
      in-depth interviews with 22 women with different socio-economic backgrounds
      residing in the capital city and a regional town. To illustrate women's
      experiences and attitudes, we used interview excerpts. RESULTS: Our findings
      indicate that there is poor communication between women and gynecologists and an
      absence of proper counseling. Women's lack of knowledge about reproductive health
      issues, poor attitudes of gynecologists, and personal barriers that women
      experience in accessing health care render preventive practices a low priority
      both for women and gynecologists. CONCLUSION: We recommend different educational
      and organizational strategies that may improve the counseling skills of
      gynecologists and ultimately reduce the prevalence of cervical cancer in Serbia.

PMID- 18820833
TI  - Epidemiology of eczema among Lebanese adolescents.
AB  - OBJECTIVE: The study aims to determine the prevalence of eczema among Lebanese
      adolescents and identify demographic, nutritional and environmental
      characteristics associated with eczema. METHODS: A cross-sectional study
      conducted on a convenient sample of 3 153 students (13-14 years) selected from
      five different provinces in Lebanon. Significant unadjusted demographic,
      nutritional and environmental variables were considered in a stepwise regression
      model. RESULTS: Ever having an itchy rash that lasted for a period more than six
      months was reported by 788 (25.0%) adolescents, while 404 (12.8%) reported ever
      having eczema. Females and passive smokers were at 1.5 increased risk of having
      eczema than their counterparts. Exercising regularly, living near a busy area,
      and frequent eating of eggs were positively associated with eczema. Finally,
      adolescents who suffered from allergic diseases, asthma (Odds ratio (OR): 1.64,
      95% CI: 1.16-2.32), rhinitis (OR: 1.35, 95% CI: 1.07-1.70) and hay fever (OR:
      2.77; 95% CI: 2.12-3.62) also reported having had eczema. CONCLUSION:
      Environmental factors were found to play an important role in the prevalence of
      eczema among adolescents.

PMID- 18820834
TI  - Bullying and subjective health among adolescents at schools in Latvia and
      Lithuania.
AB  - OBJECTIVES: To investigate the prevalence of bullying among adolescents in Latvia
      and Lithuania and to study its association with self-rated health, health
      complaints, and life satisfaction. METHODS: A total of 3417 students in Latvia
      and 5626 in Lithuania were surveyed using the Health Behaviour Study among School
      aged Children 2001/2002 (HBSC) questionnaire and research protocol. RESULTS:
      Being a victim, bully, or bully/victim was reported by 30.1% adolescents in
      Latvia and 52.3% in Lithuania with the highest proportion reporting being a
      victim. Bullying was associated with poor subjective health and low life
      satisfaction. CONCLUSIONS: The factors explaining the difference of bullying
      prevalence between both countries should be studied to develop effective anti
      bullying interventions relevant to local conditions.

PMID- 18820835
TI  - Detection and treatment of HIV and hepatitis virus infections in Swiss
      correctional facilities.
AB  - OBJECTIVES: The aim of the study was to obtain an overview on diagnostic and
      therapeutic activities concerning hepatitis A, B, C virus and HIV in Swiss
      prisons. METHODS: A standardized questionnaire was sent to 91 prisons in the
      German and Italian speaking parts in October 2004; 41 institutions (45%) answered
      the questionnaire. RESULTS: In almost all prisons serological examinations were
      not done routinely, but were provided when demanded by inmates or recommended by
      the medical service. Vaccination against hepatitis A or B infection and
      initiation of antiviral therapy was possible in most institutions. CONCLUSIONS:
      Most of the prisons investigated offered diagnostic and antiviral treatment for
      hepatitis virus and HIV infections. A reported problem was the discontinuation of
      ongoing treatments or vaccination cycles after discharge. In some cases deficient
      funding was an obstacle.

PMID- 18820836
TI  - Recurrent lymphomatous meningitis treated with intra-CSF rituximab and liposomal
      ara-C.
AB  - BACKGROUND: The most frequent central nervous system complication of systemic non
      Hodgkin's lymphoma (NHL) is lymphomatous meningitis (LM). OBJECTIVE: A clinical
      series to test the feasibility of combining intra-CSF liposomal ara-C and
      rituximab for the treatment of recurrent LM. DESIGN: Clinical series of 14
      patients with CSF positive lymphomatous meningitis. SETTING: Tertiary-care
      university medical center. RESULTS: Fourteen patients with recurrent,
      cytologically positive lymphomatous meningitis were treated. All 14 received
      liposomal ara-C and rituximab utilizing an Ommaya reservoir. Six patients also
      received involved-field radiotherapy (brain only two patients; brain and spine
      two patients; spine only two patients). Best response to treatment included 10
      partial responses and four with progressive disease. Estimated median duration of
      response was 4.0 months (range 1-6 months). Survival ranged from 1.5 to 7 months
      with an estimated median of 5 months, four patients remain alive and continue to
      be followed. Cause of death was progressive neurological disease in 7, systemic
      disease in 1, and combined systemic and neurological disease in 2 patients.
      CONCLUSIONS: The combination of intra-CSF liposomal ara-C and rituximab
      administered in this schedule appears to have no additive toxicity and has modest
      palliative activity in patients with recurrent LM.

PMID- 18820837
TI  - Localization and expression of a 70 kDa protein in goat spermatozoa having
      Na(+),K(+)-ATPase inhibitory and arylsulphatase A activities.
AB  - We have previously isolated and purified a goat sperm protein of 70 kDa molecular
      weight designated as P70 and characterized it as an inhibitor of Na(+),K(+)
      ATPase. Our study reveals that the first 10 amino acid residues from the N
      terminal end of P70 has high degree of homology with arylsulphatase A from mice,
      pig and human. Indirect immunofluorescence study shows the presence of the
      protein on goat sperm surface. Furthermore, live goat sperm and the extract of
      peripheral sperm plasma membrane proteins exhibit arylsulphatase A's desulphation
      activity. The P70 remains on the head surface of in vitro capacitated cauda
      epididymal sperm as shown by positive immunofluorescence staining of cauda sperm.
      Immunoblot and flow cytometric studies corroborate the above findings. The
      presence of P70 on capacitated cauda sperm surface suggest a possible role of
      this protein in sperm zona pellucida binding. In the present report we
      demonstrate arylsulphatase A like activity in P70 and describe its localization
      and expression in goat sperm.

PMID- 18820838
TI  - Regulation of T-type Cav3.1 channels expression by synthetic glucocorticoid
      dexamethasone in neonatal cardiac myocytes.
AB  - The effect of the dexamethasone (Dex) on the regulation of the T-type Ca(2+)
      channel expressions was investigated in primary cultures of neonatal rat
      ventricular myocytes. We found that Dex (1 microM) increases the T-type Ca(2+)
      current (I(CaT)) associated with an increase in Ca(v)3.1 mRNA amount. We isolated
      the upstream region from Ca(v)3.1 encoding gene and tested the activity of the
      promoter in transfected ventricular myocytes. We found a minimal Dex-responsive
      region that displayed putative glucocorticoid receptor (GR) and nuclear factor
      kappa-B (NFkappaB) targets. The GR selective antagonist, RU38486 (10 microM),
      nearly turned off the transcriptional activity of Ca(v)3.1 encoding gene, and an
      NFkappaB inhibitor, pyrrolodine dithiocarbonate (10 microM), completely abolished
      the Dex-induced mRNA increase. However, Dex-induced GR and NFkappaB synthesis and
      nuclear translocation were not timely related to Ca(v)3.1 mRNA increase. These
      results indicate that both GR and NFkappaB were necessary, but not sufficient, to
      trigger the increase in Ca(v)3.1 mRNA amount. This study showed the relationship
      between glucocorticoid and T-type channels up-regulation that may be involved in
      cardiac development and pathology.

PMID- 18820839
TI  - Alternate HMQC experiments for recording HN and HC-correlation spectra in
      proteins at high throughput.
AB  - Alternate implementations of the SOFAST-HMQC experiment are described. In these
      alternate SOFAST-HMQC experiments (ALSOFAST-HMQC) excitation of the magnetization
      of interest is achieved by non-selective rf pulses while preserving the
      equilibrium polarization of passive spins. This alternate excitation scheme also
      allows the incorporation of a novel sensitivity enhancement protocol which has
      been most recently developed by Brutscher and coworkers and which permits
      simultaneous detection of both the x- and y-components of the indirectly detected
      t(1)-interferograms without the need to introduce additional rf pulses and
      delays. We show that the ALSOFAST HC-HMQC experiment, which implements an
      alternate means of frequency selection, enables the detection of methyl
      resonances with large secondary proton chemical shifts. This is achieved by
      selecting coherences of interest via a frequency selective carbon inversion
      pulse. Detailed comparisons between SOFAST- and the presented ALSOFAST-HMQC
      experiment reveals a considerable degree of mutual complementarity.

PMID- 18820840
TI  - A novel beta-mannanase with high specific activity from Bacillus circulans
      CGMCC1554: gene cloning, expression and enzymatic characterization.
AB  - A DNA fragment of 2,042 bp containing a novel beta-mannanase gene, man5A, was
      identified from the genome of the mannan-degrading bacterium Bacillus circulans
      CGMCC1554. The open reading frame of man5A comprised 978 bp encoding a protein of
      326 amino acids with a predicted molecular weight of 32 kDa. The amino acid
      sequence of the encoded mannanase, MAN5A, showed the highest identity (78.5%) to
      beta-mannanases belonging to glycosyl hydrolases family 5. The gene man5A was
      efficiently expressed in Escherichia coli and Pichia pastoris with the highest
      activity of 541 U/ml in a 3-L fermenter. Recombinant MAN5A purified from E. coli
      had a high specific activity of 4,839 U/mg, which is much higher than that of
      enzymes that showed high sequence identity. The enzyme showed maximum activity at
      pH 7.6 and 60 degrees C and resistance to trypsin. After hydrolysis of LBG,
      oligomannosides accounted for 76% of the hydrolysis products. All these
      properties collectively make MAN5A a better candidate than current mannanases for
      use in the food and feed industry.

PMID- 18820843
TI  - [120th year of the Viennese Clinical Weekly and the internal medicine specialty].

PMID- 18820844
TI  - [The Viennese Clinical Weekly and the Austrian Society for Pneumology].

PMID- 18820845
TI  - [The Viennese Clinical Weekly and the Austrian Society of Physicians].

PMID- 18820846
TI  - [Low protein diet in the treatment of chronic renal failure: effective, but
      barely used].

PMID- 18820847
TI  - [Needle-stick injuries--how common are they in reality].

PMID- 18820848
TI  - Virchow's cellular pathology: 150th anniversary.

PMID- 18820849
TI  - [Asymmetric dimethylarginine (ADMA): A cardiovascular risk factor].

PMID- 18820850
TI  - [Bisphosphonate-associated osteonecrosis of the jaw].
AB  - Intravenous application of bisphosphonates (BP) represents an established
      therapeutic strategy of tumor-associated bone metastasis and severe
      hypercalcemia. Patients can develop osteonecrosis of the jaw (ONJ) as a side
      effect of this therapy. The diagnosis of ONJ is based on three criteria: a)
      patients have been or are currently treated with BP; b) a deficiency in wound
      healing, which is in 70-80% associated with necrotic alveolar bone,
      characteristically exposed, is present for at least 8 weeks and c) no
      radiotherapy of the head and neck was performed. The suppression of bone
      turnover, concomitant with high functional load of the alveolar bone, and the
      subsequent accumulation of microfractures are considered the main pathologic
      factors of this disease. The cumulative incidence of ONJ lies approximately
      between 1 and 10% in oncologic patients, being associated with the antiresorptive
      potency and the respective molecular structure of the BPs. Patients with multiple
      myeloma develop ONJ more frequently than patients with other oncological diseases
      such as metastasizing breast- and prostate cancer, a fact that may also be due to
      the higher transfusion/injection frequency of BP in these patients. Dental
      treatment strategies are responsible for the occurrence of ONJ in approximately
      80% of cases. Based on a clinical staging, patients can be grouped into three
      categories and should receive the corresponding treatment regime. Prospective
      clinical studies are required for a better understanding of etiology and
      pathogenesis of ONJ to make treatment, risk estimation and prognosis of ONJ more
      accurate.

PMID- 18820851
TI  - Colobiliary fistula: a rare complication of Crohn's disease.

PMID- 18820852
TI  - Reduction of plasma asymmetric dimethylarginine in obese patients with chronic
      kidney disease after three years of a low-protein diet supplemented with keto
      amino acids: a randomized controlled trial.
AB  - BACKGROUND: Levels of the endogenous nitric oxide synthase inhibitor asymmetric
      dimethylarginine (ADMA) are elevated in chronic kidney disease (CKD) and may
      contribute to vascular complications. In this study we tested the hypothesis that
      elevated ADMA can be reduced in obese CKD patients by long-term administration of
      a low-protein diet supplemented with keto-amino acids. PATIENTS AND METHODS: In a
      long-term prospective double-blind placebo-controlled randomized trial, we
      evaluated for a period of 36 months a total of 111 CKD patients (54 men, 57
      women) aged 22-76 years with obesity (BMI >or= 30 kg/m(2)) and an inulin
      clearance rate (C(in)) of 22-40 ml/min/1.73 m(2). All patients were on a low
      protein diet containing 0.6 g protein/kg BW per day and 120-125 kJ/kg BW per day.
      The diet was randomly supplemented with keto-amino acids at a dosage of 100 mg/kg
      BW per day (66 patients, Group I); 65 patients received placebo (Group II).
      RESULTS: During the study period, the glomerular filtration rate decreased
      slightly in Group I (C(in) from 32.4 +/- 12.6 to 29.8 +/- 8.6 ml/min/1.73 m(2))
      and more markedly in Group II (from 33.2 +/- 12.6 to 23.2 +/- 98.4 ml/min/1.73
      m(2), P < 0.01). BMI decreased significantly in Group I (from 32.0 +/- 3.3 to
      26.1 +/- 4.0 kg/m(2), P < 0.01) and was linked to reduced volume of visceral fat
      measured by MRI (P < 0.01). Reduction of BMI in Group II was not significant. In
      Group I, there was a significant decrease in the plasma level of ADMA (from 2.5
      +/- 0.5 to 1.3 +/- 0.4 micromol/l, P < 0.01), but ADMA remained unchanged in
      Group II. A further remarkable finding in Group I was reduction in the plasma
      concentration of pentosidine (from 480 +/- 170 to 320 +/- 120 microg/l, P < 0.01)
      and decrease of proteinuria (from 3.8 +/- 2.24 to 1.6 +/- 1.0 g/24 h, P < 0.02).
      Plasma adiponectin rose in Group I (P < 0.01). Analysis of the lipid spectrum
      revealed a mild but significant decrease in total cholesterol and LPD-cholesterol
      (P < 0.02), more pronounced in Group I. There was also a decrease in plasma
      triglycerides in Group I (from 3.9 +/- 1.6 down to 2.2 +/- 0.6 mmol/l, P < 0.01)
      and a decrease in glycated hemoglobin (from 7.2 +/- 1.4% to 4.2 +/- 0.8%, P <
      0.02). CONCLUSION: Compared with the placebo group, long term co-administration
      of a low-protein diet and keto-amino acids in CKD patients with obesity led to
      decreases of ADMA, visceral body fat and proteinuria. Concomitant decreases of
      glycated hemoglobin, LDL-cholesterol and pentosidine may also contribute to the
      delay in progression of renal failure.

PMID- 18820853
TI  - Needlestick injuries among health care workers: occupational hazard or avoidable
      hazard?
AB  - OBJECTIVES: The objective of this study was to describe the mechanisms and
      preventability of occupational percutaneous blood exposure of healthcare workers
      through needlestick injuries and to discuss rational strategies for prevention.
      METHODS: To calculate the preventability, we surveyed in a first step the number
      and kind of needlestick injuries and in a second step the reasons for the
      injuries and the working conditions of the healthcare workers. Both data sets
      were collected in independent anonymous questionnaire covering occupational blood
      exposure among healthcare workers in a German university hospital. RESULTS:
      Needlestick injuries were caused through unsafe procedures, difficult working
      conditions and unsafe devices. On average, 50.3% (n = 492/978) of all needlestick
      injuries could have been avoided by the use of safety devices, whereas only 15.2%
      could have been prevented by organizational measures. In our study, 31.5% (n =
      503/1598) of participant healthcare workers had sustained at least one
      needlestick injury in the past twelve months. The rate of underreporting was
      about 75%. After introduction of safety devices, 91.8% of the healthcare workers
      reported being satisfied with the anti-needlestick devices and 83.4% believed
      that safety devices would increase the safety of the work environment.
      CONCLUSIONS: Occupational exposure to blood is a common problem among healthcare
      workers. The introduction of safety devises is one of the main starting points
      for avoidance of needlestick injuries, and acceptance among healthcare workers is
      high. Further targets for preventive measures, such as training in safe working
      routines, are necessary for improvement of safe work conditions.

PMID- 18820854
TI  - Incidence and predictability of amiodarone-induced thyrotoxicosis and
      hypothyroidism.
AB  - OBJECTIVES: To determine the incidence and predictability of amiodarone-induced
      thyrotoxicosis (AIT) and hypothyroidism (AIH) in patients with cardiomyopathy.
      PATIENTS AND METHODS: A total of 72 patients (mean age 69 +/- 11 years) living in
      an area previously endemic for thyroid disease but with currently sufficient
      iodine intake were enrolled in this prospective study. All participants were
      treated with amiodarone for the first time. The course of thyroid function in
      patients with normal thyroid morphology and in those with goiter was monitored
      over a median follow-up period of eight months in 71 (98.6%) patients. RESULTS:
      Of 72 participants, 18 (25.0%) had a morphologically normal thyroid gland as
      evidenced by sonography. The prevalence of thyroid dysfunction before initiation
      of amiodarone was 37.6% (27 of 72) with almost equal distribution between
      hypothyroidism and hyperthyroidism (14 and 13 patients). After treatment with
      amiodarone, thyroid dysfunction was diagnosed in 56.8% (25 of 44) of the patients
      without preexisting dysfunction. Of these 25 patients, nine (36%) developed
      either subclinical or overt AIH and 16 (64.0%) developed either subclinical or
      overt AIT. Although 61.1% (44 of 72) had normal thyroid function before
      initiation of amiodarone, this number decreased to 26.7% (19 of 71, P < 0.001)
      after treatment. Factors such as (99m)Tc-pertechnetate scan uptake, thyroid
      autoimmunity, age, thyroid autonomy or abnormal thyroid morphology were not
      significantly associated with the development of thyroid dysfunction.
      CONCLUSIONS: Prevalence of thyroid dysfunction was high in elderly patients
      treated with amiodarone. Cases of AIT and AIH occurred in patients with and
      without preexisting thyroid disorders. Because of the high incidence of
      amiodarone-induced thyroid dysfunction, regular testing of thyroid function is
      mandatory during and following amiodarone treatment.

PMID- 18820855
TI  - Heterogeneity of traumatic injury of the tricuspid valve: a report of four cases.
AB  - Tricuspid valve injury causing severe tricuspid regurgitation is the most common
      cardiac complication following blunt chest trauma. We present four cases with
      different clinical presentations that included pleural effusion, arrhythmias,
      cyanosis, peripheral edema and dyspnea, with varying onset of symptoms.
      Echocardiographic evaluation and intraoperative findings in these patients
      revealed a broad spectrum of injury to the tricuspid valve including papillary
      muscle and chordal rupture, chordal elongation and leaflet perforation. Because
      surgical treatment is required in most patients and since the diagnosis is often
      delayed, we believe that early echocardiographic evaluation is required in all
      patients with blunt chest trauma, in particular if clinical symptoms of right
      heart failure are present.

PMID- 18820856
TI  - Fatal fulminant sepsis due to a cat bite in an immunocompromised patient.
AB  - Pasteurella multocida infections in humans can present as localized infections of
      soft tissues surrounding the lesions, as respiratory tract infections or as
      systemic infections with slow or fulminant development. Over 90% of human
      infections are cases of wound infections or abscesses related to a bite, scratch,
      or licking of skin lesions by a cat or dog. Severe systemic diseases such as
      pneumonia, lung abscess, peritonitis, endocarditis, meningitis and sepsis are
      also well known, especially in patients with underlying medical conditions. In
      this paper we report on an immunocompromised patient who was bitten by an unknown
      cat and very quickly developed fulminant sepsis, dying 70 hours after the cat
      bite, despite all the intensive care, therapy and reanimation he was given.
      Unfortunately, he asked for medical help too late. We emphasize the need for
      primary healthcare to provide more information to patients at risk of infections
      from contact with animals and to warn them about the possible consequences of
      injuries, even when the animals are pets.

PMID- 18820857
TI  - [The use of erythropoiesis-stimulating proteins in anemic patients with malignant
      diseases].

PMID- 18820858
TI  - [Laudation for Prof. Dr. Gerhard Giebisch on the occasion of the bestowal of the
      honorary membership of the OGIM].

PMID- 18820859
TI  - [Laudation for Univ. Prof. Dr. Klaus Lechner on the occasion of the bestowal of
      the honorary membership of the OGIM].

PMID- 18820861
TI  - Complications of total thyroidectomy performed by surgical residents versus
      specialist surgeons.
AB  - PURPOSE: Surgeon inexperience has been defined as a significant predictor of
      deleterious outcome in thyroid surgery; however, the safety of training programs
      in which residents are the primary surgeons is controversial. The objective of
      this prospective study was to compare the complication rates of total
      thyroidectomy (TT) performed by residents with those of TT performed by
      specialist surgeons in similar patient groups. METHODS: Between April 2001 and
      May 2007, 144 patients underwent TT at our hospital. For 75 operations, the
      primary surgeon was a resident under the direct supervision of the attending
      surgeon, and for 69 operations, the primary surgeon was the experienced attending
      surgeon. Pre-and postoperative vocal cord examinations and serum calcium level
      evaluations were carried out in all patients. RESULTS: The rates of temporary
      (unilateral) recurrent laryngeal nerve (RLN) palsy were 2.66% vs 2.17% after TT
      performed by the residents vs the attending surgeon, respectively. There were no
      significant differences in the incidences of temporary hypoparathyroidism (20% vs
      20.28%), permanent (unilateral) RLN palsy, hematoma, infection, seroma, and
      incidental parathyroidectomy between the two groups. CONCLUSION: The complication
      rates of TT performed by residents and attending surgeons were similar. Thus,
      residents can perform TT safely and effectively under the direct supervision of a
      senior surgeon. Ultimately, strict adherence to the contemporary principles of
      thyroid surgery is of paramount importance.

PMID- 18820860
TI  - Remodeling of the immunoinflammatory network system in elderly cancer patients:
      implications of inflamm-aging and tumor-specific hyperinflammation.
AB  - Although it is generally accepted that aging increases postoperative morbidity
      and mortality rates, the underlying mechanism remains unknown. The present review
      evaluates the clinical implications of remodeling the immunoinflammatory status
      with reference to inflammaging and tumor-specific hyperinflammation. We conducted
      a Medline/PubMed search for articles investigating factors related to aging and
      their effects on postoperative outcomes. Inflamm-aging results in both decreased
      immunity to exogenous antigens and increased auto-reactivity, whereby the
      beneficial effects of inflammation devoted to the neutralization of harmful
      agents early in life become detrimental late in life. Cancer also represents an
      immunologic challenge, which upregulates the systemic immune response. Thus,
      tumor-related hyperinflammation and inflamm-aging synergistically lead to the
      systemic priming of inflammatory mediators preoperatively; then, surgical stress
      acts as the second hit, increasing the risk of an exaggerated postoperative
      inflammatory response. Age-related molecular events may place elderly patients at
      greater risk of postoperative complications which could result in death. For
      regulating uncontrolled hyperinflammation, the clinical advantages of
      perioperative immunonutrition or steroids have been advocated; however, double
      blind, randomized, controlled trials of pharmacologic modulation therapy are
      needed.

PMID- 18820862
TI  - Evaluation of pain experienced during breast ductal endoscopy.
AB  - PURPOSE: Ductal endoscopy is valuable for the differential diagnosis of bloody
      nipple discharge; however, the pain associated with this procedure has not been
      evaluated. This study aims to assess the pain experienced by patients during
      ductal endoscopy. METHODS: We studied a consecutive series of women who underwent
      ductal endoscopy, to investigate the cause of bloody nipple discharge. The
      procedure was performed using standard local anesthesia (lidocaine 1% 10 ml
      without epinephrine, involving nipple block and periaureolar administration).
      Patients were asked to score the level of pain with a visual analog scale, 1, 4,
      7, 12, 17, 22, 27, and 32 min after the procedure, and describe their overall and
      maximum pain. RESULTS: This series comprised 20 women aged from 27 to 68 years
      old. The overall pain (mean +/- SE) score was equal to 5.8 +/-0.3, and the
      maximum pain score was 8.3 +/- 0.2. The peak of pain corresponded with when the
      dilator was inserted through the sphincter. The group in which the dilator was
      inserted after 4 min experienced more intense maximum and overall pain after 7,
      12, 17 and 22 min. CONCLUSIONS: Pain is an important factor in ductal endoscopy,
      and peaks relatively early. A standard, baseline local lidocaine dose of greater
      than 10 ml may be necessary at the beginning of the procedure. Late insertion of
      the dilator seems to be an indicator of the force of the procedure.

PMID- 18820863
TI  - Factors affecting postoperative morbidity and mortality in isolated coronary
      artery bypass graft surgery.
AB  - PURPOSE: This study was conducted to investigate predictors of mortality before
      and after isolated coronary artery bypass grafting (CABG). METHODS: Single
      institutional data on risk factors and mortality were collected for 8890 patients
      who underwent isolated CABG by the same group of surgeons. The relationship
      between risk factors and outcome was assessed using univariate and multivariate
      analyses in two risk models: a preoperative model (model 1) and then a pre-,
      intra-, and postoperative model (model 2). RESULTS: The mean age of the patients
      (25.4% women and 74.6% men) was 58.5 +/- 9.7 years. Fifty-five (0.6%) patients
      died after surgery. Hypercholesterolemia was the most common comorbidity factor
      (61.1%), followed by hypertension, a smoking habit, recent myocardial infarction
      (MI) <21 days, and diabetes. Postoperative tamponade, graft occlusion, and MI
      (0.01%) were the least common complications. The patients spent 39.7 +/- 33.9 h
      in the intensive care unit (ICU) postoperatively. Patients were followed up for a
      minimum of 30 days. The multivariate analysis of our preoperative risk model
      revealed that the best predictors of operative mortality were a history of
      diabetes, hypertension, previous CABG, the presence of angina, arrhythmia,
      Canadian Cardiovascular Society Classification (CCS) of grade III or IV, ejection
      fraction (EF) < or =30%, three-vessel disease, and left main disease. CONCLUSION:
      After surgery, and with the inclusion of all the pre-, intra-, and postoperative
      variables into model two, the following were revealed to be prognostic factors
      for in-hospital mortality: a history of diabetes, hypertension, the presence of
      angina, CCS grades III or IV, EF -30%, absence of internal mammary artery (IMA)
      use, prolonged cardiopulmonary bypass (CPB) time, and prolonged ICU stay.

PMID- 18820864
TI  - Clinical spectrum of internal hernia: a surgical emergency.
AB  - PURPOSE: To define the indicators of bowel ischemia caused by congenital or
      acquired internal hernia, based on our 10-year experience in one center. METHODS:
      We reviewed the medical records, imaging studies, and operative findings of 20
      patients who underwent surgery for an internal hernia at our medical center
      between 1995 and 2005. The clinical characteristics and related indicators of the
      patients with, and those without bowel ischemia were compared and analyzed
      statistically. RESULTS: The subtypes of congenital internal hernia (CIH) included
      transmesenteric (n = 6, 60%), paraduodenal (n = 2, 20%), and pericecal (n = 2,
      20%) hernia. The abdominal surgical procedures preceding acquired internal hernia
      (AIH) were Roux-en-Y anastomosis (n = 6, 60%) and appendectomy (n = 3, 30%).
      Transmesenteric hernia was the most prevalent type of CIH in children. Abdominal
      rebound tenderness, advanced leukocytosis (>18 000/mm(3)), or a high level of
      manual band form (>6%) were the positive predictive factors for bowel ischemia,
      whereas a history of chronic intermittent abdominal pain was a negative
      indicator. No recurrence was noted during the 10-year study period. The overall
      mortality rate was 20%, attributable to enteral bacteria sepsis in all cases.
      CONCLUSION: Internal hernia is a rare but lethal condition. Early diagnosis and
      prompt surgical intervention provide the only chance of a successful outcome.

PMID- 18820865
TI  - Pathological predictors for lymph node metastasis in T1 colorectal cancer.
AB  - PURPOSE: To clarify pathological predictor for lymph node metastasis in T1
      colorectal cancer. METHODS: One hundred and sixty-four patients who underwent
      surgery for single T1 colorectal cancer were reviewed. The pathological
      differentiations of non-well differentiation, invasion depth (> or =2 000
      microm), lymphatic channel involvement, venous invasion, and tumor budding were
      selected as candidate predictors. Tumor budding was estimated according to the
      definition proposed by Ueno et al. (Gastroenterology 2004; 127:385-394). The
      lymph node status was set for the endpoint. Logistic regression model was applied
      to analyze the predictors. RESULTS: Lymph node involvement was observed in 9.8%.
      The positive rates were 13.4% for the pathological differentiations of non-well
      differentiation, 51.8% for invasion depth (> or =2 000 microm), 6.1% for
      lymphatic channel involvement, 8.5% for venous invasion, and 14.6% for tumor
      budding. The pathological differentiations of non-well differentiation (P <
      0.001) and tumor budding (P = 0.002) were significantly associated with lymph
      node metastasis in multivariate analysis. When either two significant factors was
      adopted for the prediction of the lymph node metastasis, the sensitivity,
      specificity, positive predictive value, and negative predictive value were 94%,
      82%, 36%, and 99%, respectively. CONCLUSION: The pathological differentiations of
      non-well differentiation and tumor budding are useful predictors for lymph node
      metastasis in T1 colorectal cancer.

PMID- 18820866
TI  - Effect of combined therapy with the antiestrogen agent toremifene and local
      hyperthermia on breast cancer cells implanted in nude mice.
AB  - PURPOSE: We evaluated the effects of combined treatment with the antiestrogen
      agent toremifene (TOR) and local hyperthermia (LHT) on the MCF-7 breast cancer
      cell line. METHODS: BALB/c mice implanted with MCF-7 cells were divided into six
      treatment groups: a control group, a TOR30 group (given 30 mg/kg/day), a TOR120
      group (given 120 mg/kg/day), an LHT group (43.5 degrees C), a TOR30 + LHT group,
      and a TOR120 + LHT group. The effects of the treatments on tumor cells, estrogen
      receptor (ER) expression, and cell cycle kinetics were measured after 21 days. We
      calculated the apoptotic index and vascular density inside the tumors and
      evaluated the efficacy of the transmigration of TOR into the tumors. RESULTS: The
      antitumor effects were significantly greater in both combined therapy groups than
      in any of the single therapy groups. Estrogen receptor expression was weaker in
      the combined therapy groups than in the single therapy groups, and there were
      more G0/G1-phase cells and fewer S-phase cells in both combined therapy groups
      than in the single therapy groups. The apoptotic index was increased and the
      tumor vascular density was decreased in the combined therapy groups. CONCLUSIONS:
      We attributed the effects of this combined therapy to the induction of apoptosis,
      the decrease in vascular density, and the increase and decrease in G0/G1-phase
      and S-phase cells, respectively, in the tumors.

PMID- 18820867
TI  - Intratumoral expression of macrophage migration inhibitory factor is correlated
      with serum C-reactive protein and interleukin-6 in patients with non-small cell
      lung cancer.
AB  - PURPOSE: To investigate if macrophage migration inhibitory factor (MIF) affects
      systemic inflammatory response in patients with non-small cell lung cancer
      (NSCLC), we studied the relationship between intratumoral MIF expression and
      serum levels of C-reactive protein (CRP) and interleukin-6 (IL-6). METHODS: mRNAs
      for MIF and beta-actin, and 18S ribosomal RNA derived from tumor-bearing and
      nontumor-bearing tissues were quantified by a quantitative reverse transcription
      polymerase chain reaction in 35 patients with NSCLC. Spearman's test was used to
      examine the correlation between the quantities of RNAs and the preoperative serum
      levels of CRP and IL-6 in the corresponding patients. RESULTS: The intratumoral
      level of MIF mRNA was significantly correlated with the serum levels of CRP (rho
      = 0.542, P = 0.0016) and IL-6 (rho = 0.532, P = 0.0173). The level of MIF mRNA in
      the non-tumor-bearing lung also showed a positive, but relatively weak
      correlation with the serum CRP level (rho = 0.418, P = 0.0148). CONCLUSION:
      Macrophage migration inhibitory factor expression in the tumor site may affect
      the systemic inflammatory response in patients with NSCLC.

PMID- 18820868
TI  - An experimental evaluation of the lactate concentration following mesenteric
      ischemia.
AB  - PURPOSE: Although a diagnosis of mesenteric necrosis can easily be made,
      mesenteric ischemia is sometimes overlooked, especially in the acute phase. We
      experimentally evaluated the time course of the lactate concentration, which may
      be a possibly useful variable in making a diagnosis of mesenteric ischemia, and
      determined how an early diagnosis can be made. METHODS: The superior mesenteric
      artery (SMA) was surgically ligated in an anesthetized pig. Blood tests,
      including a blood gas analysis, were done using samples from the superior
      mesenteric vein (SMV), hepatic vein, femoral vein, and artery until 6 h after SMA
      ligation. RESULTS: There were no variables in any samples that showed a
      significant change within 4 h after SMA ligation except for samples taken from
      the SMV. All acidosis-related variables had changed significantly within 6 h
      after ischemia. Among them, the lactate concentration only in the SMV was
      observed to have increased significantly within one hour after SMA ligation.
      CONCLUSIONS: Currently available peripheral blood tests, including tests using
      blood obtained from the hepatic vein, do not enable the detection of mesenteric
      ischemia within 4 h after onset. In a case in which an exploratory laparotomy is
      performed, the measurement of the lactate concentration in SMV is thus considered
      to be a useful supplementary test for making a prompt diagnosis of mesenteric
      ischemia in an early phase.

PMID- 18820869
TI  - Oxymatrine attenuates intestinal ischemia/reperfusion injury in rats.
AB  - PURPOSE: Intestinal ischemia/reperfusion (I/R) is a common and serious clinical
      condition. The anti-inflammatory and anti-apoptotic properties of oxymatrine, the
      extract from a traditional Chinese herb, Sophora flavescens Ait, have been shown
      to protect the liver from I/R injury and attenuate colitis. The objective of this
      study was to investigate if oxymatrine could attenuate intestinal I/R injury
      induced in rats. METHODS: The experimental design consisted of three groups of 24
      Wistar rats each: a sham-operation group (control group), a group subjected to
      intestinal I/R and then given saline (saline group), and a group subjected to
      intestinal I/R and then given oxymatrine (oxymatrine group). Intestinal I/R was
      induced by occluding the superior mesenteric artery for 45 min. Six rats from
      each group were killed at selected time points, and blood and intestinal samples
      were collected. RESULTS: Morphological alteration, reduction of gamma-glutamyl
      transpeptidase (gamma-GGT) activity, and increased cell apoptosis confirmed
      intestinal I/R injury. The oxymatrine group had a significantly lower
      histological score and apoptosis index than the saline group, demonstrating that
      the preadministration of oxymatrine attenuated gut damage. Moreover, oxymatrine
      inhibited the production of lipid peroxides (LPO), decreased the serum levels of
      tumor necrosis factor (TNF)-alpha, and downregulated expression of phosphorylated
      p38 mitogen-activated protein kinase, Fas, and FasL, which had been elevated by
      I/R. CONCLUSIONS: These results provide further evidence of the anti-inflammatory
      and anti-apoptotic activities of oxymatrine, which may become a potent drug for
      protecting the intestines against I/R injury.

PMID- 18820870
TI  - Chylothorax due to tuberculosis lymphadenopathy: report of a case.
AB  - While pulmonary tuberculosis is a very frequent infection, chylothorax is an
      unusual manifestation of tuberculous disease. A 71-year-old woman with
      chylothorax is herein presented. The ductus thoracicus was ligated and
      lymphadenomegaly, which was adjacent to diaphragm, was resected. Based on the
      findings of various tests, a diagnosis of tuberculosis lymphadenitis was made.
      The patient was administered antituberculosis chemotherapy and has since remained
      asymptomatic for 1 year after the operation. In conclusion, tuberculosis
      lymphadenomegaly may lead to the development of chylothorax. The combination of
      appropriate surgical and medical treatment is an effective therapeutic strategy
      for this pathology.

PMID- 18820871
TI  - Sternal wound dehiscence after transverse thoracosternotomy for bilateral lung
      transplantation: report of a case.
AB  - Transverse thoracosternotomy is the standard approach for bilateral lung
      transplantation (BLT), but all measures must be taken to prevent breakdown of the
      sternal wound. We report a case of sternal dehiscence with subcutaneous and
      peristernal air collections, which occurred 1 month after BLT, performed through
      a transverse thoracosternotomy, in a 38-year-old man. Surgical exploration
      revealed that the sternal wires had cut through the bone, causing air leakage of
      both lungs. We repaired the injured lungs and reapproximated the sternum;
      however, a pseudo-joint of the sternum developed postoperatively. We report the
      clinical course of this post-transplant patient to highlight the impact and
      management of sternal dehiscence.

PMID- 18820872
TI  - A malignant peripheral nerve sheath tumor of the mediastinum in a patient with
      neurofibromatosis type 1: report of a case.
AB  - Malignant peripheral nerve sheath tumor (MPNST) is rare, but its association with
      neurofibromatosis type 1 (NF1) is well known. A 56-year-old man with NF1 was
      referred to our hospital for investigation of dyspnea. Computed tomography showed
      a huge mass occupying the right thorax and invading the inferior vena cava. A
      salvage resection was performed to alleviate the developing hypoxemia.
      Histological examination confirmed an MPNST. The tumor regrew rapidly and the
      patient died 6 weeks after the resection. This case report reinforces the
      importance of monitoring patients with NF1 carefully because of their increased
      risk of the development of malignant neoplasms.

PMID- 18820873
TI  - Repair of an infected aortic aneurysm using an aortic allograft and a venous
      autograft: report of a case.
AB  - We describe the successful surgical treatment of an unusual type of infected
      aortic aneurysm. The aneurysm emerged around the distal part of the ascending
      aorta and the proximal part of the arch and involved the innominate artery. The
      infection was attributed to prolonged catheter placement in the right jugular
      vein for intravenous hyperalimentation several years earlier. We repaired the
      aneurysm using an aortic allograft and a venous autograft under antegrade
      selective cerebral perfusion with deep hypothermia. Pathological examination
      revealed a pseudoaneurysm. The patient recovered well and has shown no sign of
      recurrence of the infection.

PMID- 18820874
TI  - Subepicardial left ventricular aneurysm with an intraventricular narrow neck on
      the avascular apical area: report of a case.
AB  - A 48-year-old hiatus hernia patient with a history of an occasional epigastric
      burning sensation for the last 10 years presented with a new onset of chest pain
      in addition to the persistence of his other symptoms. An apical left ventricular
      aneurism was found on 64-slice computed tomographic angiography. Coronary
      angiography confirmed the diagnosis. No coronary lesion was found and the apical
      region of the left ventricle was avascular. He was operated on under the
      suspected preoperative possible diagnoses of left ventricular apical aneurysm, a
      pseudoaneurysm, or a diverticulum. Macroscopically, a subepicardial whitish
      aneurysmal region with a weakened wall was seen at the apical part of the left
      ventricle. The size of the lesion was 3 x 3 cm. The aneurysm did not have an
      extracardiac neck. When the aneurysm site was opened, a sclerotic aneurysm wall
      and a narrow neck below the incised sac was found; and the neck was communicating
      with the left ventricular cavity. The aneurysm site was resected and closed with
      a linear closure technique by using pledget-supported sutures. The termination of
      cardiopulmonary bypass was uneventful. The patient left the intensive care unit
      on the first postoperative day and was discharged from hospital on the 4th
      postoperative day. A subepicardial left ventricular aneurysm should therefore
      also be considered in the differential diagnosis of atypical chest pain.

PMID- 18820875
TI  - Laparoscopic spleen-preserving distal pancreatectomy with conservation of the
      splenic artery and vein: report of three cases.
AB  - Between March 2003 and March 2007, three patients with benign pancreatic tumors
      underwent a planned laparoscopic spleen-preserving distal pancreatectomy with
      conservation of the splenic artery and vein. Four trocars were placed, and an
      endoscopic linear stapler was used to transect of the pancreas. The perioperative
      data and surgical outcomes were examined. This procedure was successfully
      completed in three patients. The mean operative time was 158.3 min, with mean
      blood loss of 14.7 ml. The postoperative pathological diagnoses included one
      insulinoma, one solid pseudopapillary tumor, and one intraductal papillary
      mucinous adenoma. The mean size of the tumors was 29.3 mm. Oral intake was
      initiated on day 1.7, and the length of postoperative hospital stay was 8.7 days
      on average. No morbidity or mortality was observed. A laparoscopic spleen
      preserving distal pancreatectomy with conservation of the splenic artery and vein
      is a safe and feasible treatment option without compromising the splenic function
      for benign or borderline malignant tumors in the distal pancreas.

PMID- 18820876
TI  - Dermoid cyst in the hepatoduodenal ligament: report of a case.
AB  - We report an unusual case of a mature cystic teratoma, or dermoid cyst, in the
      hepatoduodenal ligament of a young woman. Mature cystic teratomas are rarely
      found in extragonadal sites, especially the hepatoduodenal ligament. Surgical
      resection remains the mainstay of therapy and is required for a definitive
      diagnosis. Patients who undergo complete resection of a mature cystic teratoma
      normally have an excellent prognosis.

PMID- 18820877
TI  - Myositis ossificans in the right inferior thoracic wall as an unusual cause of
      lower thoracic-upper abdominal pain: report of a case.
AB  - We report a case of thoracic wall myositis ossificans (MO) located anterior to
      the ninth rib, causing right lower thoracic-upper abdominal pain. The diagnosis
      was based on the findings of ultrasonography (US) and computed tomography (CT).
      Numerous disorders can be included in the differential diagnosis of right lower
      thoracic-upper abdominal pain, so we must first establish if the pain is somatic
      or visceral in origin. Somatic pain in this region can be caused by traumatic
      muscle pain, overuse myalgia, costochondritis, or thoracic wall malignancies.
      Although rare, MO should also be considered in the differential diagnosis of pain
      and thoracic wall masses in this region. As the calcifications may not be seen on
      a plain chest X-ray in the early course of this condition, superficial tissue US
      or CT should be performed to establish the diagnosis.

PMID- 18820878
TI  - Successful treatment of adrenocortical carcinoma with pulmonary metastasis in a
      child: report of a case.
AB  - Adrenocortical carcinoma (ACC) in childhood is rare: in 2002, only three new
      cases were reported in Japan. Although there is no established therapeutic
      management system, margin-free complete surgical excision of the tumor is very
      important to a satisfactory outcome. We report a case of ACC with bilateral
      pulmonary metastasis in a 10-year-old boy. Preoperative chest computed tomography
      (CT) showed pulmonary metastasis with near-water density. The patient was treated
      successfully with complete surgical resection of the primary tumor and adjuvant
      chemotherapy, including mitotane. After bilateral lung surgery for the metastatic
      lesions, the plasma dehydroepiandrosterone sulfate level became negative.

PMID- 18820879
TI  - [Atypical vascular supply from the coeliac trunk. Recurrent bleeding from a
      duodenal ulcer].
AB  - Hemorrhagic duodenal ulcers should primarily be controlled by endoscopy. In cases
      of recurrent bleeding or if bleeding cannot be controlled endoscopically, open
      surgery is the gold standard. Rarely, atypical origin of arteries or additional
      atypical arteries may lead to further unexpected hemorrhagic recurrences and
      angiography with surgical intervention is the treatment of choice. In this
      article a rare case of an atypical visceral artery connecting the coeliac trunk
      and the gastroduodenal artery leading to recurrent bleeding from a duodenal ulcer
      is presented.

PMID- 18820880
TI  - [Interdisciplinary management of thoracic wall tumors: indication, technique, and
      results of interscapulothoracic amputation].
AB  - Interscapulothoracic amputation of the upper extremity, described for the first
      time by Berger in 1887, has undergone a change of indication. Originally
      performed in traumatic injuries of the shoulder or arm, it has been done in
      radical resection of malignancies of the upper extremity, axilla, or the
      surrounding thoracic wall. Particularly it is performed in tumors which cannot be
      controlled by neoadjuvant therapies or locally by radiation. The indication,
      technique, and results of such amputation are discussed by presenting our
      patients operated on with the procedure. Although this treatment is combined with
      a loss of function and body integrity, it is safe and sufficiently radical. The
      loss of function and integrity may be compensated by prosthetic reconstitution.

PMID- 18820881
TI  - [Colorectal cancer metastasis. Frequency, prognosis, and consequences].
AB  - BACKGROUND: In about 50% of colorectal cancer cases, metastases are responsible
      for tumour-specific death. This study examines influences on survival after
      diagnosis of metastases and conclusions that can be drawn from the time pattern
      of a progressive disease course. METHODS: The background was provided by Munich
      Cancer Registry database (Germany). Population-based, good follow-up, high
      quality of clinical data, and results comparable to those of other cancer
      registries stand for validity of these data. RESULTS: Number of positive lymph
      nodes is the best prognostic factor. However, since metastasis may be initiated
      before diagnosis of the primary tumour, growth of the primary tumour and the
      metastases may be two autonomous processes. Thus survival following metastasis is
      almost unrelated to prognostic factors from the primary tumour, and median
      survival time after diagnosis of metastases is therefore almost comparable with
      17 months. From the distribution of survival time after diagnosis of the primary
      tumour, the time from initiation of metastases to their diagnosis can be
      estimated at about 6 years. This means that metastases diagnosed synchronously
      with the primary tumour (M1) were initiated 6 years before detection of the
      primary tumour and also that metastases diagnosed during follow-up had already
      started before therapy of the primary tumour. In consequence, positive lymph
      nodes are an indicator but not a cause of metastases. CONCLUSIONS: Specific time
      relations support the hypothesis that all metastases were initiated before
      diagnosis of the primary tumour. This hypothetic model has a high explanatory
      potential, also for evidence of the missing survival benefit from radical lymph
      node dissection.

PMID- 18820882
TI  - [A flap simulator for training in local defect coverage].
AB  - The Hannover Medical School (Germany) developed the"Flap Lab I" flap simulator, a
      practical improvement to surgeon training. It provides realistic conditions for
      understanding and following the principles for planning and performing local
      flaps for coverage of skin defects. The Flap Lab I has proved to be a very good
      training model in several training courses. This article introduces among others
      the Z-flap, reverse Z-flap (so-called hanging man), and Limberg flap.

PMID- 18820883
TI  - [Duodenum-preserving pancreatic head resection: technique according to Beger,
      technique according to Frey and Berne modifications].
AB  - In chronic pancreatitis chronic pain is the most frequent indication for surgery.
      Because symptoms are often caused or maintained by an inflammatory mass in the
      head of the pancreas, resection procedures are superior to pure surgical
      drainage. The pancreatoduodenectomy (PD) and the duodenum-preserving pancreatic
      head resection (DPPHR) are safe and effective techniques resulting in long
      lasting pain relief in about 80% of patients. Randomized controlled trials (RCTs)
      show initial functional advantages for the organ-preserving DPPHR compared to PD,
      but these advantages are lost during follow-up, most likely because neither
      operation prevents a progressive loss of exocrine and endocrine function.
      Nevertheless the less invasive DPPHR should be regarded as the procedure of
      choice. The technique of DPPHR described by Beger was modified by Frey to an
      extended drainage procedure with local head excision; the Berne modification
      offers a technically less demanding option with comparable extent of resection.
      While results in terms of pain relief, quality of life and organ function are
      comparable between the three DPPHR techniques, the technical aspect of a simpler
      procedure favors the Berne modification.

PMID- 18820887
TI  - Expression of the endocannabinoid system in the bi-potential HEL cell line:
      commitment to the megakaryoblastic lineage by 2-arachidonoylglycerol.
AB  - The role of the endocannabinoid system in haematopoietic cells is not completely
      understood. We investigated whether human erythroleukemia (HEL) cells were able
      to bind, metabolise and transport the main endocannabinoids, anandamide (AEA) and
      2-arachidonoylglycerol (2-AG). We also investigated whether AEA or 2-AG could
      modulate HEL differentiation. Although able to internalise both endocannabinoids,
      HEL cells had the machinery to metabolise 2-AG only, since they were devoid of
      the enzymes needed to synthesise and degrade AEA. Nonetheless, the intracellular
      transport of exogenous AEA might be required to activate the vanilloid receptors,
      with yet unknown implications for vascular biology. On the contrary, 2-AG
      appeared to play a role in lineage determination. Indeed, 2-AG itself drove HEL
      cells towards megakaryocytic differentiation, as it enhanced expression of beta3
      integrin subunit, a megakaryocyte/platelet surface antigen, and glycoprotein VI,
      a late marker of megakaryocytes; in parallel, it reduced the amount of messenger
      RNA encoding for glycophorin A, a marker of erythroid phenotype. All these
      effects were mediated by activation of CB(2) cannabinoid receptors that triggered
      an extracellular signal-regulated kinase-dependent signalling cascade. In
      addition, classical inducers of megakaryocyte differentiation reduced 2-AG
      synthesis (although they did not affect the binding efficiency of CB(2)
      receptors), suggesting that levels of this endocannabinoid may be critical for
      committing HEL cells towards the megakaryocytic lineage.

PMID- 18820888
TI  - [Complex surgical procedures in orthopedics and trauma surgery. A contribution to
      the proposal procedure for the DRG system in 2009].
AB  - Since the DRG system was introduced in 2003/2004 the system for remuneration has
      been continually modified in conjunction with input from specialized medical
      associations. As part of this development of the payment system, the criteria for
      classification of a diagnosis-related group were further expanded and new
      functions were added. This contribution addresses the importance of the complex
      surgical procedures as criteria for subdivision of the DRG case-based lump sums
      in orthopedics and trauma surgery.

PMID- 18820889
TI  - [Metatarsal fractures].
AB  - Generally nondisplaced metatarsal fractures can be treated nonoperatively.
      Fracture angulation of more than 10 degrees or fracture displacement of more than
      3-4 mm are a valid indication for open or closed reduction. Fractures of the
      metatarsal bases are often associated with Lisfranc injury. Special attention
      must be paid to proximal fractures of the fifth metatarsal (avulsion, Jones,
      proximal diaphyseal fracture). Dislocated midshaft fractures of the first and
      fifth metatarsals should be treated operatively to realign foot geometry.
      Subcapital fracture malalignment causes post-traumatic metatarsalgias. Stress and
      children's fractures are treated most times nonoperatively.

PMID- 18820890
TI  - [Anterograde intramedullar K wire osteosynthesis for subcapital metatarsal
      fracture].

PMID- 18820891
TI  - [Compartment syndrome of the lower leg and foot. Anatomy and pathophysiology].
AB  - Due to the unique anatomy and pathophysiology involved, a compartment syndrome
      (CS) of the lower leg and foot is prone to develop sequelae that demand operative
      reconstruction. Moreover, the two regions are closely related. Although research
      into various pathophysiological areas is revealing specific complexities, aspects
      of the foot's compartmental anatomy remain controversial, perhaps because of
      methodological reasons. This may result in particular practices for diagnosing
      and treating CS in this region, which are discussed in this article.

PMID- 18820893
TI  - [Structured psychiatric assessment of risk for violent recidivism in juvenile
      offenders].
AB  - The psychiatric assessment of violence in youth represents a critical and
      essential part of forensic expertise and clinical practice. New methodical
      approaches are offered by structured risk rating scales and checklists which
      encompass psychopathy. The recently translated German version of Structured
      Assessment of Violence Risk in Youth (SAVRY), which is based on the Historical,
      Clinical, Risk Management Scheme (HCR 20), was evaluated in a sample of
      forensically assessed youth (n=83) regarding the predictive validity for criminal
      recidivism. Receiver operating characteristic (ROC) analyses attested medium
      (general delinquency), moderate (violent reoffending) and high (serious violent
      reoffending) effect strength, depending of the type of offence. Survival analyses
      showed that juveniles rated as high risk for violence were significantly faster
      and in a higher proportion recidivistic than those with a moderate or low risk.
      The results indicate the applicability of risk assessment instruments for German
      juveniles. Approaches for preventive, therapeutic and reintegrating measures are
      demonstrated, taking relapse patterns and dynamic risk aspects into
      consideration.

PMID- 18820892
TI  - [Correlations between risk gene variants for schizophrenia and brain structure
      anomalies].
AB  - The specific etiologies of schizophrenia are largely unknown. Genetic
      predisposition constitutes an important, however, not exclusive risk factor for
      the development of schizophrenia. In recent years, a number of candidate genes
      were identified and have been consistently replicated. Magnetic resonance imaging
      studies have characterized structural changes in brain morphology, such as
      ventricular enlargement or volume reduction of the medial temporal structures and
      the superior temporal gyrus. Several studies have found correlations between gene
      variants and changes of brain morphology in schizophrenia patients and healthy
      controls. In this review, publications examining correlations of schizophrenia
      susceptibility gene polymorphisms and structural brain anomalies in patients and
      healthy controls are described. An overview and a critical reflection of the
      current research are outlined. The results of genome-wide studies will soon
      provide a multitude of additional schizophrenia susceptibility genes. If and to
      what extent these genes exert an influence on the brain structure in the healthy
      and the diseased, can be clarified by gene structure correlations. Given the many
      possible gene-gene and gene-environment interactions, most variants will probably
      not show simple interactions with sizable effects.

PMID- 18820894
TI  - [Alzheimer's disease. Molecular pathology, animal models, and current treatment].
AB  - The currently approved but only mildly efficient drugs against Alzheimer's
      disease treat merely the symptoms. Genetic, neuropathological, and biochemical
      data support the importance of the amyloid hypothesis of Alzheimer's disease, at
      the moment the most influential hypothesis. Many treatment strategies have been
      performed based on this hypothesis and were markedly successful in preclinical
      animal models. Unfortunately the treatment is still unsuccessful in humans. This
      could be due to the animal models showing marginal behavioural deficits but no
      Alzheimer-like nerve cell loss, although they all developed a more or less
      pronounced plaque load. Today we know however that Alzheimer plaques are not
      mainly responsible for the cell loss. Therefore novel animal models have been
      developed that show age-dependent axonal degeneration, massive neuronal loss, and
      robust behavioural deficits. Successful treatment of an animal model with such
      robust deficits would be very likely better suited to transferral into the
      clinic. The final validation or disproof of individual Alzheimer hypotheses and
      their resulting treatment strategies can however be obtained only after clinical
      proof.

PMID- 18820895
TI  - [Its not always due to mumps!].
AB  - A painless swelling of the parotid gland with non-specific symptoms and
      uncharacteristic blood values is not necessarily caused by mumps. On the
      contrary, this should be examined with targeted imaging, conventional X-rays of
      the thorax on two levels and for further differential diagnostic clarification,
      computed tomography of the thorax in order to search for further causes.

PMID- 18820896
TI  - [The role of surgery in locally advanced prostate cancer].
AB  - Recent retrospective monocentric studies have demonstrated favorable 15-year
      cancer-specific survival (CSS) rates of up to 86% using radical prostatectomy as
      part of multimodal treatment in locally advanced prostate cancer (T3-4, N0, M0).
      Patients most likely to benefit from surgery include those with a biopsy Gleason
      score < or =8, a prostate-specific antigen level <20 ng/ml, and cT3a cancer.
      Patients must be informed that additional treatment after prostatectomy might be
      necessary (30-70%; radiotherapy, hormonal therapy). Urinary incontinence may
      occur in up to 20%, and severe incontinence (more than two pads per day) is
      observed in up to 6%.Adjuvant radiotherapy should be considered individually and
      is not routinely recommended. Extended pelvic lymphadenectomy should be
      performed, although it has only a minor impact on survival. However, even in
      patients with lymph node micrometastasis, 10-year CSS can be achieved in 85.6%
      with the use of additional hormonal therapy. Cancer progression can possibly be
      delayed by surgical excision of the primary tumor, even in patients with
      metastasis. The existing data must be checked in prospective randomized trials.

PMID- 18820897
TI  - Lack of an association between GHR exon 3 polymorphism and diabetic nephropathy
      in the Genetics of Kidneys in Diabetes (GoKinD) population.

PMID- 18820898
TI  - Comparative and morphological analysis of commonly used autografts for anterior
      cruciate ligament reconstruction with the native ACL: an electron, microscopic
      and morphologic study.
AB  - Ligaments and tendons are similar in composition but differ in proportion and
      arrangement. Tendons are being used as grafts for the ACL reconstruction. Their
      microscopic structure has not been sufficiently studied and compared to the
      native ACL. A null hypothesis was declared stating that the anterior cruciate
      ligament should be histological, morphologically and functionally different from
      the tendon grafts used for ACL reconstruction. We investigated similarities and
      differences of the structure of ACL and tendons used as a graft tissue for ACL
      reconstruction. In this study, standardized samples of quadriceps, hamstrings
      (semitendinosus and gracilis) and patellar tendons, and the ACL were harvested
      from 26 autopsies (average age 36.4) and were investigated using light and
      electron microscopy, immunohistochemistry and morphometry. The thickness of the
      collagen fibrils, collagen organization and diameter, the fibril/interstitium
      ratio, density of fibroblasts and blood vessels, and distribution of the collagen
      type I, III and V fibrils were analyzed. The semitendinosus showed the highest
      density of fibroblasts and blood vessels, while the gracilis the highest
      fibril/interstitium ratio. No differences regarding the thickness of collagen
      fibrils and distribution of fibrils were found. The ACL had the highest
      concentration of type III and V collagen fibrils as well as elastic fibers. The
      histological and ultrastructural appearance of the ACL differs from those of the
      tendons used as graft, for ACL reconstruction. Its ultrastructure is varied and
      complex, with its collagen fibers bundles lying in many directions.

PMID- 18820899
TI  - Stability of the pstS transcript of Escherichia coli.
AB  - The pst operon of Escherichia coli is composed of five genes that encode a high
      affinity phosphate transport system. As a member of the PHO regulon, pst
      transcription is activated under phosphate shortage conditions. Under phosphate
      replete conditions, the pst operon also functions as a negative regulator of the
      PHO genes. Transcription of pst is initiated at the promoter located upstream to
      the first gene, pstS. Immediately after its synthesis, the primary transcript of
      pst is cleaved into shorter mRNA molecules. The transcription unit corresponding
      to pstS is significantly more abundant than the transcripts of the other pst
      genes due to stabilisation of pstS mRNA by a repetitive extragenic palindrome
      (REP) structure downstream to the pstS locus. The presence of the REP sequence
      also results in an increased level of PstS proteins. However, the surplus level
      of PstS proteins produced in the presence of REP does not contribute to the
      repressive role of Pst in PHO expression.

PMID- 18820900
TI  - Structure, function and biosynthesis of carotenoids in the moderately halophilic
      bacterium Halobacillus halophilus.
AB  - Inhibitor studies and mutant analysis revealed a C(30) pathway via 4,4'
      diapophytoene and 4,4'-diaponeurosporene to 4,4'-diaponeursoporene-4-oic acid
      esters related to staphyloxanthin in Halobacillus halophilus. Six genes may be
      involved in this biosynthetic pathway and could be found in two adjacent gene
      clusters. Two genes of this pathway could be functionally assigned by functional
      pathway complementation as a 4,4'-diapophytoene synthase and a 4,4'-diapophytoene
      desaturase gene. These genes were organized in two operons together with two
      putative oxidase genes, a glycosylase and an acyl transferase ortholog. Pigment
      mutants were obtained by chemical mutagenesis. Carotenoid analysis showed that a
      white mutant accumulated 4,4'-diapophytoene due to a block in desaturation. In a
      yellow mutant carotenogenesis was blocked at the stage of 4,4'-diaponeurosporene
      and in an orange mutant at the stage of 4,4'-diaponeurosporene-4-oic acid. The
      protective function of these pigments could be demonstrated for H. halophilus
      after inhibition of carotenoid synthesis by initiation of oxidative stress. A
      degree of oxidative stress which still allowed 50% growth of carotenogenic cells
      resulted in the death of the cells devoid of colored carotenoids.

PMID- 18820901
TI  - Determination of critical micelle concentration with the rotating sample system.
AB  - A novel experimental approach using the rotating sample system (RSS) is proposed
      here for the determination of the critical micelle concentration (CMC) of
      surfactants. The RSS has been conceived in our laboratory as a convection
      platform for physicochemical studies and analyses in microliter-sized sample
      drops. The scheme allows for vigorous rotation of the drop despite its small size
      through efficient air-liquid mechanical coupling. Thus, changes in surface
      properties of aqueous samples result in corresponding modulation of the
      hydrodynamic performance of the RSS, which can be utilized to investigate
      interfacial phenomena. In this work, we demonstrate that the RSS can be used to
      study the effects of surfactants on the surface and in the bulk of very small
      samples with hydrodynamic electrochemistry. Potassium ferrocyanide is employed
      here with cyclic voltammetry to probe the air-water interface of solutions
      containing Triton X-100. The CMC of this surfactant determined using this
      approach is 140 ppm, which agrees well with reported values obtained with
      conventional methods in much larger samples. The results also demonstrate that
      besides the CMC, variations in bulk rheological properties can also be
      investigated in very small specimens using the RSS with a simple method.

PMID- 18820902
TI  - Digital bioanalysis.
AB  - Digital microfluidics has recently emerged as a new paradigm in the world of lab
      on-a-chip technology. A wide variety of bioanalyses have been successfully
      implemented in this format. This paper reviews the various techniques that have
      been adapted to digital microfluidic systems, and the current state of the field.

PMID- 18820903
TI  - Synthesis and binding site characteristics of 2,4,6-trichlorophenol-imprinted
      polymers.
AB  - 2,4,6-Trichlorophenol (2,4,6-TCP)-imprinted micro- and submicrospheres prepared
      by precipitation polymerization were compared with templated materials obtained
      by conventional bulk polymerization. The influence of the type and amount of
      functional monomer, the type and amount of cross-linker, polymerization
      temperature, porogen, and the ratio of template molecule and functional monomer
      to cross-linker on the size of the obtained particles were investigated. UV-Vis
      spectrophotometer experiments revealed that the microsphere polymers provided
      higher affinity to the template in contrast to imprinted polymers prepared by
      bulk polymerization. The binding properties of the microspheres, including
      binding isotherms and affinity distribution, were studied via Freundlich isotherm
      affinity distribution (FIAD) analysis. The obtained results indicated that
      microspheres prepared by precipitation polymerization provided superior rebinding
      properties during equilibrium binding in contrast to bulk polymers and
      submicrosphere polymers. Moreover, release experiments showed that 80% of rebound
      2,4,6-TCP was released from the imprinted microspheres within the first 2 h,
      while more intimately bound 2,4,6-TCP molecules were released in the following 40
      h. The morphologies and porosities of the resulting imprinted materials were
      characterized by scanning electron microscopy (SEM) and Brunauer-Emmett-Teller
      (BET) analysis, respectively. The microsphere polymers exhibited a regular
      spherical shape with a high degree of monodispersity to the corresponding bulk
      polymers. Furthermore, the micro- and submicrospheres were characterized by
      narrow distribution of pores in contrast to a heterogeneity index of m = 0.6647
      for the microsphere imprinted polymer.

PMID- 18820905
TI  - Bioconversion of soy isoflavones daidzin and daidzein by Bifidobacterium strains.
AB  - Twenty-two strains of Bifidobacterium, representative of eight major species of
      human origin, were screened for their ability to transform the isoflavones
      daidzin and daidzein. Most of the strains released the aglycone from daidzin and
      12 gave yields higher than 90%. The kinetics of growth, daidzin consumption, and
      daidzein production indicated that the hydrolytic activity occurred during the
      growth. The supernatant of the majority of the strains did not release the
      aglycone from daidzin, suggesting that cell-associated beta-glucosidases (beta
      Glu) are mainly responsible for the metabolism of soybean glyco-conjugates. Cell
      associated beta-Glu was mainly intracellular and significantly varied among the
      species and the strains. The lack of beta-Glu was correlated with the inability
      to hydrolyze daidzin. Although S-equol production by anaerobic intestinal
      bacteria has been established, information on S-equol-producing bifidobacteria is
      contradictory. In this study, 22 bifidobacteria failed to transform daidzein into
      reduced metabolites under all the experimental conditions, excluding any role in
      the reductive pathway of daidzein toward the production of S-equol. These results
      suggest that selected probiotic strains of Bifidobacterium can be used to speed
      up the release of daidzein, improving its bioavailability for absorption by
      colonic mucosa and/or biotransformation to S-equol by other intestinal
      microorganisms.

PMID- 18820906
TI  - Diversity of the resident microbiota in a thermophilic municipal biogas plant.
AB  - Biogas plants continuously convert biological wastes mainly into a mixture of
      methane, CO2 and H2O-a conversion that is carried out by a consortium of bacteria
      and archaea. Especially in the municipal plants dedicated towards waste
      treatment, the reactor feed may vary considerably, exposing the resident
      microbiota to a changing variety of substrates. To evaluate how and if such
      changes influence the microbiology, an established biogas plant (6,600 m3, up to
      600 m3 biogas per h) was followed over the course of more than 2 years via
      polymerase chain reaction-denaturing gradient gel electrophoresis of 16S rRNA
      genes and subsequent sequencing. Both the bacterial and the archaeal community
      remained stable over the investigation. Of the bacterial consortium, about half
      of the sequences were in decreasing order of occurrence: Thermoacetogenium sp.,
      Anaerobaculum mobile, Clostridium ultunense, Petrotoga sp., Lactobacillus
      hammesii, Butyrivibrio sp., Syntrophococcus sucromutans, Olsenella sp.,
      Tepidanaerobacter sp., Sporanaerobacter acetigenes, Pseudoramibacter
      alactolyticus, Lactobacillus fuchuensis or Lactobacillus sakei, Lactobacillus
      parabrevis or Lactobacillus spicheri and Enterococcus faecalis. The other half
      matched closely to ones from similar habitats (thermophilic anaerobic
      methanogenic digestion). The archaea consisted of Methanobrevibacter sp.,
      Methanoculleus bourgensis, Methanosphaera stadtmanae, Methanimicrococcus
      blatticola and uncultured Methanomicrobiales. The role of these species in
      methane production is discussed.

PMID- 18820907
TI  - Genetically engineered production of 1,1'-bis-valienamine and validienamycin in
      Streptomyces hygroscopicus and their conversion to valienamine.
AB  - The antifungal agent validamycin A is an important crop protectant and the source
      of valienamine, the precursor of the antidiabetic drug voglibose. Inactivation of
      the valN gene in the validamycin A producer, Streptomyces hygroscopicus subsp.
      jinggangensis 5008, resulted in a mutant strain that produces new secondary
      metabolites 1,1'-bis-valienamine and validienamycin. The chemical structures of
      1,1'-bis-valienamine and validienamycin were elucidated by 1D and 2D nuclear
      magnetic resonance (NMR) spectroscopy in conjunction with mass spectrometry and
      bioconversion employing a glycosyltransferase enzyme, ValG. 1,1'-Bis-valienamine
      and validienamycin exhibit a moderate antifungal activity against Pellicularia
      sasakii. Chemical degradation of 1,1'-bis-valienamine using N-bromosuccinimide
      followed by purification of the products with ion-exchange column chromatography
      only resulted in valienamine, whereas parallel treatments of validoxylamine A,
      the aglycon of validamycin A, resulted in an approximately 1:1 mixture of
      valienamine and validamine, underscoring the advantage of 1,1'-bis-valienamine
      over validoxylamine A as a commercial source of valienamine.

PMID- 18820908
TI  - Phage Mu-driven two-plasmid system for integration of recombinant DNA in the
      Methylophilus methylotrophus genome.
AB  - A phage Mu-driven two-plasmid system for DNA integration in Escherichia coli
      genome has been adjusted for Methylophilus methylotrophus. Constructed helper
      plasmids with broad-host-range replicons carry thermo-inducible genes for
      transposition factors MuA and MuB. Integrative plasmids that are only replicated
      in E. coli could be mobilized to M. methylotrophus and contained mini-Mu unit
      with a short terminus of Mu DNA, Mu-attL/R. Mini-Mu unit was integrated in the M.
      methylotrophus genome via mobilization of the integrative plasmid to the cells
      carrying the helper in conditions of thermo-induced expression of MuA and MuB. In
      this system, mini-Mu unit was mainly integrated due to replicative transposition,
      and the integrated copy could be amplified in the M. methylotrophus chromosome in
      the presence of helper plasmid. A kan-gene flanked by FRT sites was inserted in
      one of the mini-Mu units, and it could be readily excised by yeast FLP
      recombinase that is encoded by the designed plasmid. The multiple Mu-driven gene
      insertion was carried out by integration of the Bacillus amyloliquefaciens alpha
      amylase gene followed by curing the KmR marker before integration of the second
      mini-Mu unit with Pseudomonas putida xylE gene encoding catechol 2,3-dioxygenase
      (C23O).

PMID- 18820909
TI  - Improved PCR method for the creation of saturation mutagenesis libraries in
      directed evolution: application to difficult-to-amplify templates.
AB  - Saturation mutagenesis constitutes a powerful method in the directed evolution of
      enzymes. Traditional protocols of whole plasmid amplification such as
      Stratagene's QuikChange sometimes fail when the templates are difficult to
      amplify. In order to overcome such restrictions, we have devised a simple two
      primer, two-stage polymerase chain reaction (PCR) method which constitutes an
      improvement over existing protocols. In the first stage of the PCR, both the
      mutagenic primer and the antiprimer that are not complementary anneal to the
      template. In the second stage, the amplified sequence is used as a megaprimer.
      Sites composed of one or more residues can be randomized in a single PCR
      reaction, irrespective of their location in the gene sequence.The method has been
      applied to several enzymes successfully, including P450-BM3 from Bacillus
      megaterium, the lipases from Pseudomonas aeruginosa and Candida antarctica and
      the epoxide hydrolase from Aspergillus niger. Here, we show that megaprimer size
      as well as the direction and design of the antiprimer are determining factors in
      the amplification of the plasmid. Comparison of the results with the performances
      of previous protocols reveals the efficiency of the improved method.

PMID- 18820910
TI  - Paradoxical concentration effect of a homodimerizing antibody against a human non
      small cell lung cancer cell line.
AB  - Drug dosing is commonly based on the dogma that, increasing the dose maximizes
      the therapeutic response until a dose level that is prohibitively toxic is
      reached. This doctrine also applies to antibody therapy, as several protocols
      have explored dose escalation. We have analyzed the effect of different amounts
      of a homophilic Herceptin targeting a human lung tumor cell line, and discovered
      that the normal dose-potency relationship does not apply. To study this
      paradoxical effect of antibody concentration on potency, we examined the
      molecular species of the homophilic Herceptin under different concentrations
      using size exclusion chromatography and gel electrophoresis. We also varied
      experimental conditions in FACS tumor targeting, such as concentration of
      antibody, membrane immobilization, temperature, and antibody homo/dimer
      immobilization. We observed that high concentrations of homophilic Herceptin
      reduce targeting, and also noted the tumor growth arrest in the xenograft mice
      after the tumor reached a critical size. The therapeutic window appears to be
      defined by tumor size and antibody concentration. Since the concentration of this
      homophilic antibody defines the optimum targeting window, our data suggest the
      therapeutic dose of antibody should be matched with the tumor burden.

PMID- 18820911
TI  - HER-2/neu mediated down-regulation of MHC class I antigen processing prevents CTL
      mediated tumor recognition upon DNA vaccination in HLA-A2 transgenic mice.
AB  - To study DNA vaccination directed against human HER-2 in the HHD mouse Tg strain,
      we created a novel HER-2-expressing syngeneic tumor transplantation model. We
      found that a DNA vaccine encoding the full length HER-2 DNA protected HHD mice
      from HER-2(+) tumor challenge by a CTL independent mechanism. A more efficient
      approach to induce HLA-A2 restricted CTLs, through immunization with a multi
      epitope DNA vaccine expressing the HLA-A2 restricted HER-2 369-377, 435-443 and
      689-697 epitopes, resulted in high numbers of peptide specific T cells but failed
      to induce tumor protection. Subsequently we discovered that HER-2 transfected
      tumor cells down-regulated MHC class I antigen expression and exhibited a series
      of defects in the antigen processing pathway which impaired the capacity to
      produce and display MHC class I peptide-ligands to specific CTLs. Our data
      demonstrate that HER-2 transfection is associated with defects in the MHC class I
      presentation pathway, which may be the underlying mechanism behind the inability
      of CTLs to recognize tumors in this HLA-A2 transgenic model. As defective MHC
      class I presentation may be a common characteristic of HER-2 expressing tumors,
      vaccines targeting HER-2 should aim at inducing an integrated immune response
      where also CD4(+) T cells and antibodies are important components.

PMID- 18820912
TI  - Does the SLC40A1 gene modify HFE-related haemochromatosis phenotypes?
AB  - Most hereditary haemochromatosis patients are homozygous for the C282Y mutation
      of the HFE gene. However, the phenotypic expression and clinical aggressiveness
      of the disease differs considerably from patient to patient. The main objective
      of this work was to study the role of variants in the SLC40A1 gene in the
      severity of iron overload and his clinical consequences in 100 Spanish probands
      homozygous for the C282Y mutation of the HFE gene. We performed automated
      sequencing of the coding regions, including intron-exon junctions of the SLC40A1
      gene. We studied the association between polymorphisms in the SLC40A1 gene and
      median values of iron removed, taking into account statistical corrections for
      multiple comparisons. No pathogenic mutations in the SLC40A1 were detected. Five
      known single nucleotide polymorphisms (SNPs) were identified, and two of them
      were associated with phenotypic characteristics. IVS1-24 C>G was associated with
      the amount of iron removed and presence of liver disease: Of the 83 patients
      finally studied for this SNP, the amount of iron removed was above the median in
      36 of 56 (64.3%) for C/C, in nine of 23(39.1%) for C/G and in zero of four (0%)
      for G/G patients (P=0.01). Liver damage was observed in 34 of 56 patients (60.7%)
      for C/C, in eight of 23 (34.8%) for C/G and in zero of four (0%) for G/G
      (P=0.01). Both associations remained significant at multivariate analysis
      (P=0.011 and P=0.023, respectively). IVS1-24 C>G on the ferroportin gene seems to
      be a genetic modifier for clinical aggressiveness of HFE1 haemochromatosis.

PMID- 18820913
TI  - Role of BCRP as a biomarker for predicting resistance to 5-fluorouracil in breast
      cancer.
AB  - PURPOSE: Chemotherapy is not only important but also necessary for the patient of
      breast cancer. Breast cancer resistance protein (BCRP), an atypical drug efflux
      pump, mediates multidrug resistance in breast cancer. The aim of this study is to
      search new substrate of BCRP. The result will guide the drug selection of
      chemotherapy in BCRP-positive breast cancer. METHODS: PA317/Tet-on/TRE-BCRP cell
      induced with doxycycline was used to screen the possible substrates of BCRP by
      MTT assay. The suspicious substrate [5-fluorouracil (5-Fu)] was further confirmed
      in PA317 and breast cancer cell MCF-7 by HLCP, apoptosis assay (staining and
      FACS) and RNAi technique. RESULTS: Mitoxantrone, 5-Fu, adriamycin, Methotrexate,
      Pirarubicin, and Etoposide were identified as substrates of BCRP. However,
      Paclitaxel, Vincristine, Vindesine, Mitomycin C, and cisplatin were not mediated
      by BCRP. 5-Fu was identified as substrate of BCRP for the first time. The further
      study showed that the intracellular retention dose of 5-Fu and the 5-Fu induced
      cellular apoptosis all decreased when BCRP highly expressed. Furthermore, 5-Fu
      accumulation and 5-Fu induced DNA damage increased when BCRP was silenced by RNAi
      in breast cancer cells. CONCLUSIONS: 5-Fluorouracil may be a specific substrate
      which can be bound by BCRP. BCRP can predict the sensitivity of breast cancer to
      5-Fu. And BCRP-targeted therapy will reverse the resistance of breast cancer to 5
      Fu.

PMID- 18820914
TI  - [Current problems of hepatitis].
AB  - New findings have been made in recent years on the various forms of the hepatitis
      virus in terms of disease course, its etiopathogenetic link with comorbidities
      and the definition of new forms in Central Europe. Epstein-Barr virus (EBV)- and
      cytomegalovirus (CMV)-induced hepatitis may occur in the so-called sero-negative
      group of hepatitis and direct demonstration of the viral genome in paraffin liver
      tissues is required to confirm the diagnosis. Since diagnosis of autoimmune
      hepatitis in daily practice may be difficult, a scoring system with simplified
      criteria has recently been developed.

PMID- 18820915
TI  - [Report of the working group on paediatric pathology].

PMID- 18820916
TI  - [Report by the working group on haematopathology].

PMID- 18820917
TI  - [Virtual microscopy in systems pathology].
AB  - Genomics and proteomics have evolved towards systems biology. The general goal
      here is the construction of complex, functional models of biological systems on
      the basis of molecular networks. Such models enable improved quality in
      interpretation and evaluation of quantitative measurements and afford a
      substantially deeper functional understanding. Systems pathology differs from
      systems biology by attaching the same importance to spatial modelling of tissue
      alterations as to gene regulatory modelling. In this way, systems pathology is
      able to deploy disease models for improved diagnosis, prognosis and therapy. In
      the present work a generic process for systems pathology is created, integrating
      gene regulatory and morphological models towards molecular disease models. For
      this purpose, fluorescent virtual microscopy will be essential as it delivers
      morphological and molecular tissue data with high spatial resolution and high
      throughput. Using epidermal differentiation as an example, it is shown how -
      using virtual microscopy - the spatiotemporal expression of biomarkers can be
      modelled by reconstructing protein networks from fluorescent tissue sections.

PMID- 18820919
TI  - [The role of endothelial cells in allograft rejection].
AB  - Endothelial cells (EC) are crucially involved in allograft rejection. They are
      prime targets of alloreactivity but also key players in the recruitment and
      extravasation of immune cells. These mechanisms also become clear in allograft
      biopsies with antibody-mediated complement deposition on EC and associated
      intracapillary accumulation of immune cells. HLA molecules are the most prominent
      targets of alloantibodies in AB0 compatible transplantation. Clinically relevant
      antibodies against other antigens such as MICA (MHC class I-related chain A) or
      the angiotensin II Type-1 receptor could also be convincingly demonstrated. The
      lack of generally available diagnostic tests for such non-HLA antibodies hampers
      their introduction into clinical practice. Alloantibodies undoubtedly cause
      allograft rejection. However, our knowledge of the molecular mechanisms
      underlying graft dysfunction in antibody-mediated rejection (AMR) is still
      fragmentary. Activation of EC by anti-endothelial cell antibodies was
      demonstrated in several experimental systems. Recent animal studies employing
      immune cell deficient transplant recipients or in-vitro assays, however, failed
      to demonstrate an immediate response of EC upon antibody binding and complement
      activation. It might therefore be considered that direct antibody- or complement
      mediated EC damage is not necessarily the leading event in acute AMR. Antibody-
      and/or complement-induced recruitment of immune cells might rather be of crucial
      importance at least in the early phases of AMR.

PMID- 18820920
TI  - [Human papillomavirus infection. Pathology and molecular pathology].
AB  - Cervical cancer is the second most frequent female malignoma worldwide and
      accounts for about 500,000 cases every year. The peak incidence lies between 35
      and 55 years of age. Persistent infections with a group of 15 so-called high-risk
      human papillomaviruses (HR-HPV) are the cause of cervical carcinogenesis of
      squamous cell carcinomas and for most of the adenocarcinomas. The transforming
      potential of HR-HPVs is based on the interaction of viral oncogene products E6
      and E7 with the cellular tumor suppressor proteins p53 and pRB. The resulting
      loss of cell cycle control sets the basis for additional, as yet only
      incompletely discovered, genetic and epigenetic changes, finally leading to
      invasive growth. Preneoplastic changes, cervical intraepithelial neoplasias, can
      be identified morphologically, thus allowing for therapeutic interventions. Since
      November 2007, the Standige Impfkommission, the German standing committee on
      immunizations, has recommended the prophylactic use of vaccines against the two
      most frequent HR-HPV genotypes, HPV-16 and HPV-18, in women age 12-17 years
      before first sexual intercourse. In addition to cervical cancer, HPV infections
      are responsible for the development of genital warts (condyloma) and a number of
      vaginal, vulvar, and anal intraepithelial neoplasias. HPV infections are usually
      transmitted sexually.

PMID- 18820921
TI  - [Classification of prosthetic loosening and determination of wear particles].
AB  - Nowaday, loosening of orthopaedic implants implies important medical and
      socioeconomic problems. Implant loosening is caused by implant infections as well
      as aseptic loosening, due to particle disease and mechanical alterations.
      Clinically we divide the implant infection into early and late infections.
      Morphologically it is possible to reliably detect the infection by quantification
      of neutrophil granulocytes. Additionally molecular methods are suitable to detect
      micro-organisms which are responsible for the prosthetic joint infection
      including their resistance to antibiotics. Particle disease may be reproducibly
      classified by the detection of different types of wear particles, particularly
      polyethylene, metal, ceramic and cement. The aetiology of the indeterminate type
      of the periprosthetic membrane is obscure, but may be associated with
      osteopathies. This classification of the periprosthetic membrane morphology
      provides clinically significant information concerning clinical management of
      implant loosening.

PMID- 18820922
TI  - [WHO classification of tumours of the CNS: revised edition of 2007 with critical
      comments on the typing und grading of common-type diffuse gliomas].
AB  - The fourth edition of the WHO classification of tumours of the CNS was published
      in 2007. Six new entities were codified: angiocentric glioma (AG); papillary
      glioneuronal tumour (PGNT); rosette-forming glioneuronal tumour of the fourth
      ventricle (RGNT); papillary tumour of the pineal region (PTPR); spindle cell
      oncocytoma of the adenohypophysis (SCO); and pituicytoma. Furthermore, six
      histological variants of well-known brain tumours have been added, partially
      because they show different biological behaviour and/or prognosis: pilomyxoid
      astrocytoma; atypical choroid plexus papilloma; medulloblastoma with extensive
      nodularity; anaplastic medulloblastoma; extraventricular neurocytoma; non
      specific variant of dysembryoplastic neuroepithelial tumour (DNT). The new
      entities and variants are discussed in this review. Moreover, the typing und
      grading of common-type diffuse gliomas, as well as the WHO grading system, are
      critically reviewed, particularly with regard to the prognostically important
      differential diagnosis of diffuse astrocytomas und oligodendrogliomas.

PMID- 18820923
TI  - [Intraepithelial neoplasia/dysplasia - histopathology in ulcerative colitis].
AB  - About 1-2% of all colorectal carcinomas (CRCs) arise from a background of chronic
      inflammatory bowel diseases (IBDs) such as ulcerative colitis (UC) or Crohn's
      disease, and around 15% of patients with IBD die from colorectal cancer.
      Intraepithelial neoplasia/dysplasia in the setting of IBD is considered a
      precancerous lesion by definition. Intraepithelial neoplasia may present itself
      either as a flat or polypoid mucosal lesion and is referred to as a dysplasia
      associated lesion or mass (DALM) in the latter case. The therapeutic consequence
      of high-grade intraepithelial neoplasia/dysplasia and/or DALM is proctocolectomy
      in most centers because of the high risk of synchronous or metachronous CRC. The
      diagnosis of ulcerative colitis-related intraepithelial neoplasia and its
      distinction from regenerative changes and sporadic adenomas (ALMs) occurring in
      UC is still one of the greatest challenges in gastrointestinal pathology. Intra-
      and interobserver variability for the distinction between low-grade
      intraepithelial neoplasia and regenerative lesions tends to be quite high. This
      is partly due to the difficult histomorphology and partly due to the relative
      rareness of this diagnosis (approximately 10% of patients with IBD).

PMID- 18820924
TI  - [U-HO1. A new cell line derived from a primary refractory classical Hodgkin
      lymphoma].
AB  - The Hodgkin cell line U-HO1 was established from a malignant pleural effusion of
      a 23-yr-old male patient during the end stage of refractory nodular sclerosing
      classical Hodgkin lymphoma (cHL). Since its establishment in 2005, U-HO1 has
      maintained stable characteristics in vitro and has a doubling time of about 4
      days under standard culture conditions. U-HO1 forms typical Reed/Sternberg cells
      in suspension, is EBV negative, lacks HLA-ABC- but expresses HLA-D- proteins/CD74
      and surface exposes CD15 together with CD30 in the absence of CD19 and CD20.
      Karyotype analysis of U-HO1 revealed a hyperdiploid karyotype with multiple
      clonal aberrations. Most significant is an elongated chromosome 2,
      der(2)t(2;10)(q35;q16.1)add(2)(p13). CGH analysis revealed the following
      imbalances: ish cgh dim(1)(p13p31)(p12q21), enh(2)(p13p23), dim(4)(q31.3qter),
      enh(6)(q22q27), enh(12), enh(18),enh(20)(q13.1pter). FISH analysis showed about
      six-fold amplification of REL and BCL-11A, thus, U-HO1 is prototypical for cHL in
      every aspect tested so far. Compared to other HL cell lines, U-HO1 proved far
      less genetically aberrant suggesting that U-HO1's imbalances suffice to cause the
      full-blown phenotype of primary refractory cHL.

PMID- 18820925
TI  - [Report by the working group on gastrointestinal pathology].

PMID- 18820926
TI  - [Molecular mechanisms and consequences of cardiac viral infections].
AB  - Molecular biological methods have confirmed the pathogenetic role of
      enteroviruses, primarily coxsackieviruses of group B (CVB), in the induction and
      maintenance of inflammatory cardiomyopathy. More recently, adenoviruses, various
      herpes viruses, and increasingly parvovirus B19 (B19) have been identified as
      potential cardiotropic agents. While cardiac myocytes are target cells for
      enterovirus and adenovirus infections with virus-induced cytolysis, B19
      associated inflammatory cardiomyopathy is characterized by infection of
      intracardiac endothelial cells of small arterioles and veins, which may be
      associated with endothelial dysfunction, impairment of myocardial
      microcirculation, penetration of inflammatory cells, and secondary myocyte
      necrosis. Recent observations showed that B19 is involved in intracellular
      calcium regulation by the viral phospholipase. B19-induced caspase activation can
      lead to proinflammatory/proapoptotic processes through dysregulation of STAT
      signaling. These cellular interactions may contribute to mechanisms by which B19
      establishes persistent infection in endothelial cells and play a critical role in
      viral pathogenesis of inflammatory cardiomyopathy.

PMID- 18820927
TI  - [Cartilage tumors of the skeleton].
AB  - Although the spectrum of benign and malignant cartilaginous bone tumors is
      extremely wide, a distinct diagnosis, even from small biopsy specimens, is almost
      always possible if radiological findings, age, clinical data, and localization
      within the skeleton as well as within the bone are considered. With limitations,
      this also holds true for distinguishing enchondromas from low-grade
      chondrosarcomas; however, extensive experience in multidisciplinary bone tumor
      diagnosis is required. In single cases, immunohistochemical findings may be
      helpful in the differential diagnosis if they are integrated into the context of
      all other findings. Because of treatment-related or prognosis-related
      consequences, collaboration with a reference center is recommended.

PMID- 18820929
TI  - Serum and bronchoalveolar lavage fluid nitric oxide levels in diffuse systemic
      sclerosis.

PMID- 18820930
TI  - Fibromyalgia subgroups: profiling distinct subgroups using the Fibromyalgia
      Impact Questionnaire. A preliminary study.
AB  - The main goal of this project was to identify the presence of fibromyalgia (FM)
      subgroups using a simple and frequently used clinical tool, the Fibromyalgia
      Impact Questionnaire (FIQ). A total of 61 women diagnosed with FM participated in
      this study. FM subgroups were created by applying a hierarchical cluster analysis
      on selected items of the FIQ (pain, fatigue, morning tiredness, stiffness,
      anxiety and depressive symptoms). We also tested for group differences on
      experimental pain, psychosocial functioning and demographic characteristics. Two
      cluster profiles best fit our data. FM-Type I was characterized by the lowest
      levels of anxiety, depressive and morning tiredness symptoms, while FM-Type II
      was characterized by elevated levels of pain, fatigue, morning tiredness,
      stiffness, anxiety and depressive symptoms. Both FM subgroups showed hyperalgesic
      responses to experimental pain. These results suggest that pain and stiffness are
      universal symptoms of the disorder but that psychological distress is a feature
      present only in some patients.

PMID- 18820931
TI  - High prevalence of rheumatoid factor associated with clinical manifestations of
      rheumatic disease in Kaingang and Guarani Indians from Southern Brazil.
AB  - The aim of the present study was to perform a screening for rheumatoid factor
      (RF) and anti-nuclear antibody in Kaingang, Guarani and Mestizos individuals from
      Mangueirinha Reservation, State of Parana, Brazil, and associate it with
      demographic and clinical data. Serum samples from 321 aborigines (125 male and
      196 female; 4-86 years old) and 180 non-Indians healthy individuals were analysed
      (62 male and 118 female; 2-81 years old). Antinuclear antibody (ANA) was tested
      by indirect immunofluorescence, and RF by agglutination in latex and
      turbidimetry. RF was higher in Kaingang when compared to Guarani (P = 0.009),
      Mestizos (P = 0.061) and non-Indians (P = 0.010). A significant increase of RF
      was observed in Kaingang women versus Kaingang men (P = 0.002) and, among the
      women, in Kaingang when compared to Mestizos and Guarani (P <or= 0.008). The
      positivity for ANA did not show significant differences between the groups.
      Clinical evaluation of RF positive individuals (n = 6) confirmed rheumatoid
      arthritis in two Kaingang Indians. Other two individuals (RF positive) will be
      under medical observation, as well as two Mestizos. The differences observed
      among the investigated groups, suggest the influence of genetic and hormonal
      factors in the development of auto antibodies in these populations.

PMID- 18820932
TI  - Autoimmune lymphoproliferative syndrome-like syndrome presented as lupus-like
      syndrome with mycobacterial joint infection evolved into the lymphoma.
AB  - The autoimmune lymphoproliferative syndrome (ALPS) and ALPS-like syndrome are
      variable clinical conditions characterized by lymphoproliferative disease,
      autoimmune cytopenias and susceptibility to malignancy. A 59-year-old woman was
      admitted to the hospital for intractable generalized pain and stiffness with
      multiple swollen joints for 2 weeks. A low-grade fever, intermittent hypotension
      and confusion were associated with the pain. The evaluation revealed multiple
      joint bony erosions with effusion and a ruptured Baker's cyst and positive AFB
      testing on the joint biopsy of the right wrist. In addition, there were a macular
      skin rash with telangiectasia and perivascular lymphocyte infiltration, a
      cytopenia without abnormal cells, a hepatosplenomegaly, a pericardial thickness
      with effusion and pleural effusion. The patient was treated with anti
      mycobacterial drugs, NSAIDs and glucocorticoids for 10 months. But with the
      symptoms worsening, the patient developed cervical lymph node enlargements and
      was diagnosed as a diffuse large B cell lymphoma with hemophagocytosis on biopsy.

PMID- 18820933
TI  - Involvement of a banana MADS-box transcription factor gene in ethylene-induced
      fruit ripening.
AB  - To investigate the regulation of MADS-box genes in banana (Musa acuminata L. AAA
      group cv. Brazilian) fruit development and postharvest ripening, we isolated from
      banana fruit a MADS-box gene designated MuMADS1. Amino acid alignment indicated
      MuMADS1 belongs to the AGAMOUS subfamily, and phylogenetic analysis indicates
      that this gene is most similar to class D MADS-box genes. Reverse transcriptase
      polymerase chain reaction (RT-PCR) analysis showed that MuMADS1 is expressed in
      the stamen and pistil of male and female flowers and in the rhizome, the
      vegetative reproductive organ of the banana plant. In preharvest banana fruit,
      MuMADS1 is likely expressed throughout banana fruit development. In postharvest
      banana ripening, MuMADS1 is associated with ethylene biosynthesis. Expression
      patterns of MuMADS1 during postharvest ripening as determined by real-time RT-PCR
      suggest that differential expression of MuMADS1 may not only be induced by
      ethylene biosynthesis associated with postharvest banana ripening, but also may
      be induced by exogenous ethylene.

PMID- 18820934
TI  - In vitro hermaphrodism induction in date palm female flower.
AB  - This study explores and reports on the gain brought to the morphogenetic aptitude
      of female date palm inflorescences through in vitro hermaphrodism induction. It
      investigates the main factors involved in the process of sex modification through
      hormonal induction, such as the floral developmental stage and hormone
      combination and concentration. It demonstrates that the vestigial stamens
      (staminodes) of female date palm flowers display a new and high capacity to
      proliferate under particular in vitro conditions, without blocking carpel's
      development, leading to morphologically typical hermaphrodite flowers. This de
      novo activation of repressed stamens was found to occur rapidly. The isolated
      pollen mother cells appear in the obtained anther's locules and undergo an
      ordinary microsporogenesis process. The data show that hermaphrodism induction
      depended heavily on both the growth regulators applied and the flower's
      developmental stage. They also confirm the early theory that suggests that
      dioecious plants come from a hermaphrodite ancestor. Such hermaphrodism control
      can provide new prospects and opportunities for the investigation of the in vitro
      self-fertilization process. It can also be useful in improving the understanding
      of the genetic mechanism involved in sex organ development in date palm.

PMID- 18820935
TI  - Brain thermal inertia, but no evidence for selective brain cooling, in free
      ranging western grey kangaroos (Macropus fuliginosus).
AB  - Marsupials reportedly can implement selective brain cooling despite lacking a
      carotid rete. We measured brain (hypothalamic) and carotid arterial blood
      temperatures every 5 min for 5, 17, and 63 days in spring in three free-living
      western grey kangaroos. Body temperature was highest during the night, and
      decreased rapidly early in the morning, reaching a nadir at 10:00. The highest
      body temperatures recorded occurred sporadically in the afternoon, presumably
      associated with exercise. Hypothalamic temperature consistently exceeded arterial
      blood temperature, by an average 0.3 degrees C, except during these afternoon
      events when hypothalamic temperature lagged behind, and was occasionally lower
      than, the simultaneous arterial blood temperature. The reversal in temperatures
      resulted from the thermal inertia of the brain; changes in the brain to arterial
      blood temperature difference were related to the rate of change of arterial blood
      temperature on both heating and cooling (P < 0.001 for all three kangaroos). We
      conclude that these data are not evidence for active selective brain cooling in
      kangaroos. The effect of thermal inertia on brain temperature is larger than
      might be expected in the grey kangaroo, a discrepancy that we speculate derives
      from the unique vascular anatomy of the marsupial brain.

PMID- 18820936
TI  - Periarticular muscle stimulation controls anterior tibial laxity after
      experimental ACL section: an experimental study.
AB  - BACKGROUND AND PURPOSE: Besides current strategies to treat potentially disabling
      anterior cruciate ligament (ACL) injury, a new and innovative approach was
      designed based on electrical stimulation of the muscle to prevent unwanted
      displacement of the tibia relative to the femur. Our aim was to measure muscular
      strain and anterior tibial translation (ATT) in a controlled study using an
      animal model of ACL-deficient knee undergoing muscular electric stimulation.
      METHODS: Seventeen cat knees under tibial anterior traction of 24.5 N were
      studied before and after ACL transection. Muscular fiber length variation was
      obtained by ultrasonomicrometry and ATT by video recordings at the beginning,
      during, and at the end of the movement. Square pulses of 0.2 ms with 5 V were
      applied in trains of 500, 100, and 20 ms simultaneously to both the quadriceps
      and hamstrings before and immediately after traction. RESULTS: Electric
      stimulation of ACL-deficient knees normalized muscular strain to values of
      control knees. An increased resistance to muscular lengthening was observed in
      stimulated knees. Stimulation before traction maintained similar ATT than control
      knees during the subsequent traction. DISCUSSION: Electric muscular stimulation
      in the ACL-deficient knee provoked periarticular muscle contraction, controlling
      ATT when time-adjusted stimulus (before traction) was used. This suggested that
      artificially inducing the muscular response could help to control anterior knee
      laxity after ACL injury.

PMID- 18820937
TI  - Reconstruction of the proximal humerus with a composite of extracorporeally
      irradiated bone and endoprosthesis following excision of high grade primary bone
      sarcomas.
AB  - INTRODUCTION: Functional reconstruction of the shoulder joint following excision
      of a malignant proximal humeral tumour is a difficult proposition. METHOD: Eleven
      patients with primary osteosarcoma or Ewing's sarcoma underwent reconstruction
      with a composite of extra-corporeally irradiated autograft with the addition of a
      long stemmed hemiarthroplasty. At a mean follow-up of 5.8 years two patients had
      died from disseminated disease and one patient had undergone amputation for local
      recurrence. The eight patients with a surviving limb were examined clinically and
      radiographically. RESULT: The mean Toronto Extremity Salvage Score was 74 and
      Musculo-Skeletal Tumour Society score 66. Rotation was well preserved but
      abduction (mean 32 degrees ) and flexion (40 degrees ) were poor. There was a
      high rate of secondary surgery, with five out of eleven patients requiring re
      operation for complications of reconstruction surgery. Radiographic estimate of
      graft remaining at follow up was 71%. There were no infections, revisions or
      radiographic failures. CONCLUSION: Whilst the reconstructions were durable in the
      medium term, the functional outcome was no better than with other reported
      reconstructive methods. The composite technique was especially useful in subtotal
      humeral resections, allowing preservation of the elbow joint even with very
      distal osteotomy. Bone stock is restored, which may be useful for future revision
      surgery in this young group of patients.

PMID- 18820938
TI  - Association of interferon-gamma and tumor necrosis factor alpha polymorphisms
      with susceptibility to vitiligo in Iranian patients.
AB  - Vitiligo is a common skin disorder that is caused by selective destruction of
      melanocytes, resulting in disfiguring loss of pigment. There are convincing
      evidences that cytokines and T cell mediated immunity may have a role in its
      pathogenesis. Given the fact that cytokine production is under genetic control,
      in this study, we have investigated IFN-gamma +874 T/A and TNF-alpha -308 G/A
      gene polymorphisms in a total of 176 vitiligo patients and 545 controls. IFN
      gamma +874 T/A and TNF-alpha -308 G/A gene polymorphisms were genotyped via
      Allele Specific Oligonucleotide PCR (ASO-PCR) method. The results showed that the
      TNF-alpha -308 G/A polymorphism was more common in vitiligo patients than
      controls (P = 0.0004). This difference was only significant between female
      patients and controls (P < 0.0001), while there was no significant difference
      between male patients and male controls (P = 0.90). The distribution of IFN-gamma
      genotypes in vitiligo patients did not differ significantly from that in control
      subjects (P = 0.56). Since the presence of A nucleotide at position -308 of TNF
      alpha gene is associated with increased cytokine production, therefore, the
      higher frequency of TNF-alpha -308 A allele in vitiligo patients compared to
      controls may be considered as a genetic susceptibility factor towards the
      development of vitiligo.

PMID- 18820939
TI  - A large duplication in LIPH underlies autosomal recessive hypotrichosis simplex
      in four Middle Eastern families.
AB  - Autosomal recessive hypotrichosis simplex (ARHS) manifests with paucity of hair
      appearing during early childhood. We assessed four affected families. We
      initially genotyped three of these families for a panel of microsatellite markers
      spanning all ARHS-associated loci and obtained data suggesting linkage to 3q27,
      encompassing LIPH, which had previously been shown to be associated with ARHS.
      Accordingly, a homozygous duplication mutation in exon 2 of this gene
      (c.280_369dup; p.Gly94_Lys123dup) was found to segregate with the disease in all
      the families. Through the identification of the first duplication mutation in the
      human LIPH gene, we provide further evidence supporting a role for the
      phospholipase signalling pathway in hair growth and differentiation.

PMID- 18820940
TI  - Detection of anti-envoplakin and anti-periplakin autoantibodies by ELISA in
      patients with paraneoplastic pemphigus.
AB  - Paraneoplastic pemphigus patients (PNP) develop a group of autoantibodies, among
      which those against envoplakin and periplakin are almost always found. Epitope
      mapping has indicated that the linker subdomains of the proteins harbor the major
      antigenic sites recognized by PNP sera. In order to detect specific
      autoantibodies for the diagnosis of PNP, we expressed recombinant proteins
      containing linker subdomains of human periplakin and envoplakin in a human kidney
      cell line, and used them as the antigens for ELISAs. We found that all of the
      sera from 16 PNP patients recognized these two recombinant proteins by ELISA, and
      sera from 20 pemphigus vulgaris (PV), 12 pemphigus foliaceus (PF), 20 bullous
      pemphigoid (BP), 2 Castleman's tumor without PNP and 20 normal controls showed
      negative results. We also expressed the extracellular domain of desmoglein 3
      (Dsg3) in the cell line, and used this recombinant Dsg3 as the ELISA antigen.
      Only 11 of our 16 PNP sera were positive, and most PV sera were positive. Our
      findings indicate that ELISAs using the recombinant proteins containing linker
      subdomains of envoplakin and periplakin expressed in a human cell line as the
      antigens are highly sensitive and specific for the diagnosis of PNP.

PMID- 18820941
TI  - Roxithromycin antagonizes catagen induction in murine and human hair follicles:
      implication of topical roxithromycin as hair restoration reagent.
AB  - Roxithromycin (RXM) is a 14-member macrolide antibiotics, with a variety of
      bioregulatory functions including anti-apoptotic activity to keratinocytes.
      Therefore, RXM has been used for many kinds of skin diseases. In this study,
      human and murine hair follicles were treated with RXM in order to find the
      possibility to cure hair loss disease such as androgenetic alopecia (AGA). In
      AGA, dihydrotestosterone signals apoptosis in dermal papilla cells in susceptible
      individuals, resting in premature termination of anagen and early entry into
      catagen. Therefore, anti-apoptotitic drug has a possibility of new candidate for
      AGA. This study revealed RXM antagonized the in vitro inhibitory effect of IFN
      gamma on proliferation of keratinocytes and induction of apoptosis in murine and
      human hair bulb. RXM increases hair elongation and inhibits catagen-like changes
      induced in vitro with IFN-gamma in murine and human hair follicles. Furthermore,
      topical 5% RXM solution effectively restores hair growth in about half of
      individuals with AGA without any local and systemic adverse effects. Therefore,
      RXM is new candidate as a hair restoration drug for AGA.

PMID- 18820942
TI  - Use of Bodipy-labeled sphingolipid and cholesterol analogs to examine membrane
      microdomains in cells.
AB  - Much evidence has accumulated to show that cellular membranes such as the plasma
      membrane, contain multiple "microdomains" of differing lipid and protein
      composition and function. These domains are sometimes enriched in cholesterol and
      sphingolipids and are believed to be important structures for the regulation of
      many biological and pathological processes. This review focuses on the use of
      fluorescent (Bodipy) labeled analogs of sphingolipids and cholesterol to study
      such domains. We discuss the similarities between the behavior of Bodipy
      cholesterol and natural cholesterol in artificial bilayers and in cultured cells,
      and the use of Bodipy-sphingolipid analogs to visualize membrane domains in
      living cells based on the concentration-dependent monomer-excimer fluorescence
      properties of the Bodipy-fluorophore. The use of Bodipy-D-erythro
      lactosylceramide is highlighted for detection of domains on the plasma membrane
      and endosome membranes, and the importance of the sphingolipid stereochemistry in
      modulating domain formation is discussed. Finally, we suggest that Bodipy
      sphingolipids may be useful in future studies to examine the relationship between
      membrane domains at the cell surface and domains enriched in other lipids and
      proteins on the inner leaflet of the plasma membrane.

PMID- 18820943
TI  - Localization of the actin-binding protein fesselin in chicken smooth muscle.
AB  - This report compares cellular localization of fesselin in chicken smooth,
      skeletal and cardiac muscle tissues using affinity purified polyclonal fesselin
      antibodies. Western blot analyses revealed large amounts of fesselin in gizzard
      smooth muscle with lower amounts in skeletal and cardiac muscle. In gizzard,
      fesselin was detected by immunofluorescence as discrete cytoplasmic structures.
      Fesselin did not co-localize with talin, vinculin or caveolin indicating that
      fesselin is not associated with dense plaques or caveolar regions of the cell
      membrane. Immunoelectron microscopy established localization of fesselin within
      dense bodies. Since dense bodies function as anchorage points for actin and
      desmin in smooth muscle cells, fesselin may be involved in establishing
      cytoskeletal structure in this tissue. In skeletal muscle, fesselin was
      associated with desmin in regularly spaced bands distributed along the length of
      muscle fibers suggesting localization to the Z-line. Infrequently, this banding
      pattern was observed in heart tissue as well. Localization at the Z-line of
      skeletal and cardiac muscle suggests a role in contraction of these tissues.

PMID- 18820944
TI  - Paternal and maternal exposure to welding fumes and metal dusts or fumes and
      adverse pregnancy outcomes.
AB  - OBJECTIVE: We assessed whether paternal exposure prior to conception and maternal
      exposure during pregnancy to welding fumes (WF) and metal dusts or fumes (MD/F)
      independently and jointly increases the risk of preterm delivery, low birth
      weight, and small-for-gestational age. METHODS: The study population was selected
      from The Finnish Prenatal Environment and Health Study of 2,568 newborns
      (response rate 94%) and included 1,670 women who worked during pregnancy of which
      68 were exposed either to WF and/or MD/F. RESULTS: The risk of SGA was related to
      maternal exposure to WF only (adjusted OR = 1.78; 95% CI 0.53-5.99), MD/F only
      (adjusted OR = 1.77; 95% CI 0.38-8.35) and both exposures (2.92; 1.26-6.78). The
      corresponding effect estimates for preterm delivery were 2.66 (0.32-22.08), 5.64
      (1.14-27.81) and for birth weight below 3,000 g 3.79 (1.09-13.19), 1.85 (0.56
      6.14) and 1.70 (0.70-4.15), respectively. There was some suggestive, inconsistent
      evidence that the risk of preterm delivery and SGA is related to paternal
      exposure to WF. CONCLUSIONS: The present results provide evidence that maternal
      exposure to WF or MD/F combination during pregnancy may reduce fetal growth and
      suggestive evidence that paternal exposure to WF may increase the risk of preterm
      delivery and small-for-gestational age. The small number of exposed women and the
      lack of data for exposure concentrations suggest the need for further study to
      verify our findings.

PMID- 18820945
TI  - Compositional characterization and imaging of "wall-bound" acylesters of Populus
      trichocarpa reveal differential accumulation of acyl molecules in normal and
      reactive woods.
AB  - Acylesterification is one of the common modifications of cell wall non-cellulosic
      polysaccharides and/or lignin primarily in monocot plants. We analyzed the cell
      wall acylesters of black cottonwood (Populus trichocarpa Torr. & Gray) with
      liquid chromatography-mass spectrometry (LC-MS), Fourier transform-infrared (FT
      IR) microspectroscopy, and synchrotron infrared (IR) imaging facility. The
      results revealed that the cell wall of dicotyledonous poplar, as the walls of
      many monocot grasses, contains a considerable amount of acylesters, primarily
      acetyl and p-hydroxycinnamoyl molecules. The "wall-bound" acetate and phenolics
      display a distinct tissue specific-, bending stress responsible- and
      developmental-accumulation pattern. The "wall-bound" p-coumarate predominantly
      accumulated in young leaves and decreased in mature leaves, whereas acetate and
      ferulate mostly amassed in the cell wall of stems. Along the development of stem,
      the level of the "wall-bound" ferulate gradually increased, while the basal level
      of p-coumarate further decreased. Induction of tension wood decreased the
      accumulation of the "wall-bound" phenolics while the level of acetate remained
      constant. Synchrotron IR-mediated chemical compositional imaging revealed a close
      spatial distribution of acylesters with cell wall polysaccharides in poplar stem.
      These results indicate that different "wall-bound" acylesters play distinct roles
      in poplar cell wall structural construction and/or metabolism of cell wall matrix
      components.

PMID- 18820946
TI  - MAGE-A1 expression is associated with good prognosis in neuroblastoma tumors.
AB  - PURPOSE: Neuroblastoma is an embryonal tumor of neuroectodermal cells. Patients
      with metastatic neuroblastoma have a poor survival rate, which has led to
      numerous efforts to develop prognostic markers. Cancer/testis-specific antigens
      MAGE-A1 and MAGE-A3 genes were proposed as minimal residual disease (MRD) markers
      in neuroblastoma, but its usefulness for this purpose is rather limited. METHODS:
      We studied 47 primary neuroblastoma tumors. RNA was extracted and cDNA was
      prepared by reverse transcription. Detection of the MAGE-A1 expression was done
      by hybridization of the RT-PCR products. We used methylation-specific-PCR to
      perform the epigenetic studies. RESULTS: We studied the MAGE-A1 and MAGE-A3
      expressions, and the MAGE-A1 expression showed significant association with tumor
      stage, absence of bone marrow infiltration and survival. A multivariate analysis
      enabled us to conclude that the MAGE-A1 expression represents a new independent
      predictive factor, which is independent of N-Myc amplification (P value = 0.000),
      age at diagnosis (P value = 0.002) or tumoral stage (P value = 0.024).
      Considering the epigenetic regulation of MAGE-A1, we analyzed its methylation
      profile, and found a significant association with its expression in tumor cells.
      Moreover, we found tumors that failed to show the MAGE-A1 expression despite the
      hypomethylated sequence, and corresponded to advanced neuroblastoma that might
      share another mechanism involved in MAGE-A1 silencing. Given the association
      described between genome-wide hypomethylation and microsatellite instability, we
      determined the MSI status of tumor samples, finding a significant correlation
      with the MAGE-A1 expression and, more specifically, with the hypomethylated
      status of this gene only in female patients. CONCLUSION: We conclude that the
      MAGE-A1 expression is associated with good prognosis in neuroblastoma.

PMID- 18820947
TI  - Inflammatory cytokines suppress NAD(P)H:quinone oxidoreductase-1 and induce
      oxidative stress in cholangiocarcinoma cells.
AB  - PURPOSE: The aim of this study was to evaluate the effect of inflammation on
      NAD(P)H: quinone oxidoreductase-1 (NQO1), the xenobiotic metabolizing and
      antioxidant enzyme protecting cells against electrophiles and reactive oxygen
      species in biliary cancer (cholangiocarcinoma) cells. METHODS: Human
      cholangiocarcinoma cell line, KKU-OCA17 and HeLa Chang liver cells were treated
      with inflammatory cytokine combinations (interferon-gamma, interleukin-1beta and
      tumor necrosis factor-alpha) for 48 h before NQO1 activity was assayed. Oxidant
      status was examined by assays of formation of nitric oxide (NO) and superoxide,
      and glutathione (GSH) levels. Expression of NQO1 was assessed by a reverse
      transcription and polymerase chain reaction. Effects of S-nitroso-glutathione
      (GSNO) were examined if the effects of inflammatory cytokines could be mimicked
      by nitric oxide donor. RESULTS: NQO1 activity in KKU-OCA17 and HeLa Chang liver
      cells was suppressed by cytokine combination. Cytokines induced formation of NO
      and suppression of redox ratios of GSH and glutathione disulfide (GSSG). GSNO
      produced the similar effects as cytokines on KKU-OCA17, in contrast, GSNO induced
      increase of NQO1 activity in HeLa Chang liver cells. The treatment of cytokines
      or GSNO suppressed expression of NQO1 in KKU-OCA17 and HeLa Chang liver cells.
      CONCLUSIONS: Inflammatory cytokines induced oxidative stress and this is
      associated with suppression of NQO1, whereas may contribute to differential
      susceptibility of biliary epithelial cells to chemical-induced cytotoxicity and
      carcinogenesis.

PMID- 18820948
TI  - Association of SIRT1 gene variation with visceral obesity.
AB  - The sirtuin SIRT1 is an important regulator of energy metabolism through its
      impact on glucose and lipid metabolism and therefore we tested the hypothesis
      that genetic variation in SIRT1 may have an effect on adiposity in a Belgian
      case/control association study. This study included 1,068 obese patients (BMI >
      or = 30 kg/m(2)) from the outpatient obesity clinic and 313 lean controls (BMI
      between 18.5 and 25 kg/m(2)). Anthropometrics were assessed by classical methods
      and visceral (VFA), subcutaneous (SFA) and total abdominal (TFA) fat areas were
      determined by a CT scan. The extent of linkage disequilibrium in SIRT1 allowed us
      to reduce the number of SNPs to two, sufficient to cover the entire gene. The two
      tagSNPs (rs7069102 and rs3818292) were analyzed by LightSNiP assays in all
      subjects. Rs3818292 genotypes were similarly distributed in cases and controls,
      whereas rs7069102 was different for the additive (P = 0.007) and dominant (P =
      0.01) model. The variant C-allele of rs7069102 reduced obesity risk with an OR of
      0.74 (P = 0.025; 95% CI 0.57-0.96) under a dominant model. In obese male
      subjects, this variant allele was associated with increased waist circumference
      (P = 0.04), WHR (P = 0.02), TFA (P = 0.03) and VFA (P = 0.005) (dominant model;
      adjusted for age and BMI). Rs3818292 was related to VFA (P = 0.005; adjusted for
      age and BMI) in obese males while in obese women, no significant associations
      were detected. Our data suggest that genetic variation in SIRT1 increases the
      risk for obesity, and that SIRT1 genotype correlates with visceral obesity
      parameters in obese men.

PMID- 18820949
TI  - Re-creation of the genetic composition of a founder population.
AB  - Human ethnic groups are frequently comprised of two or more founder populations.
      One of these founding populations is often available for contemporary sampling.
      We describe a method for reconstructing the composition of a missing founder
      population using the highly informative haplotypes comprising the HLA system. An
      application of the method is demonstrated using bone marrow registry samples of
      African Americans. We use contemporary samples of African Americans and European
      Americans to derive haplotypes of the West African founder populations. This
      approach may also be useful for reconstructing ancestral haplotypes for regions
      elsewhere in the genome.

PMID- 18820950
TI  - Niche differentiation between diploid and hexaploid Aster amellus.
AB  - The maintenance of separated diploid and polyploid populations within a contact
      zone is possible due to both prezygotic and postzygotic isolation mechanisms.
      Niche differentiation between two cytotypes may be an important prezygotic
      isolating mechanism and can be studied using reciprocal transplant experiments.
      We investigated niche differentiation between diploid and hexaploid Aster amellus
      in their contact zone in the Czech Republic. Diploid populations are confined to
      habitats with low productivity, whereas hexaploid populations occur in habitats
      with both low and high productivity. Thus, we chose three diploid populations and
      six hexaploid populations, three in each of the two different habitat types. We
      analyzed habitat characteristics and carried out reciprocal transplant
      experiments in the field using both seeds and adult plants. Sites of diploid and
      hexaploid populations differed significantly in vegetation and soil properties.
      The mean number of juveniles was higher at sites of home ploidy level than at
      sites of foreign ploidy level, suggesting niche differentiation between the two
      cytotypes. On the other hand, transplanted adult plants survived at all sites and
      juvenile plants were able to establish at some sites of the foreign cytotype.
      Furthermore, the mean number of juveniles, survival, and flowering percentages
      were higher at home sites than at foreign sites, indicating local adaptation. We
      conclude that niche differentiation between the two cytotypes and local
      adaptation within each cytotype may contribute to the maintenance of diploid and
      hexaploid populations of A. amellus in their contact zone. Moreover, further
      factors, such as differences in flowering phenology and exclusion of minority
      cytotypes, should also be considered.

PMID- 18820951
TI  - Technical viability of the production, partial purification and characterisation
      of inulinase using pretreated agroindustrial residues.
AB  - The present work aimed to study the viability of the use of sugarcane molasses
      and corn steep liquor (CSL) in a sequential inulinase production performing an up
      stream pretreatment of these agroindustrial residues. A sequential strategy was
      used applying three central composite rotatable designs (CCRDs) to optimise
      medium composition, followed by a down-stream step. The medium containing 150 g
      L(-1) molasses, 50 g L(-1) CSL and 6 g L(-1) yeast extract, yielded a maximum
      inulinase production of 1,294 +/- 7 U mL(-1), after 72 h of fermentation. A down
      stream evaluation was carried out using an expanded bed of Streamline DAE resin
      (Pharmacia), with and without the up-stream treatment. The results showed that
      the enzyme could not be recovered from the non-pretreated medium, whereas a yield
      of 91% was obtained in the adsorption stage from the medium prepared with the up
      stream treatment, showing the viability of producing the enzyme inulinase from
      agroindustrial residues using the integrated process.

PMID- 18820952
TI  - The sagittal balance of the spine in children and adolescents with osteogenesis
      imperfecta.
AB  - In severe forms of osteogenesis imperfecta, multiple compression fractures of the
      spine, as well as vertebral height shortening could be responsible for an
      increased thoracic kyphosis or a diminished lumbar lordosis. Theses progressive
      changes in sagittal shapes of the trunk could be responsible for a global
      sagittal trunk imbalance. We compare the parameters of sagittal spinopelvic
      balance in young patients with OI to those parameters in a control group of
      healthy volunteers. Eighteen patients with osteogenesis imperfecta were compared
      to a cohort of 300 healthy volunteers. A standing lateral radiograph of the spine
      was obtained in a standardized fashion. The sacral slope, pelvic tilt, pelvic
      incidence, lumbar lordosis, thoracic kyphosis, T1 and T9 sagittal offset were
      measured using a computer-assisted method. The variations and reciprocal
      correlations of all parameters in both groups according to each other were
      studied. Comparison of angular parameters between OI patients and control group
      showed an increased T1T12 kyphosis in OI patients. T1 and T9 sagittal offset was
      positive in OI patients and negative in control group. This statistically
      significant difference among sagittal offsets in both groups indicated that OI
      patients had a global sagittal balance of the trunk displaced anteriorly when
      compared to the normal population. Reciprocal correlations between angular
      parameters in OI patients showed a strong correlation between lumbar lordosis
      (L1L5 and L1S1) and sacral slope. The T9 sagittal offset was also strongly
      correlated with pelvic tilt. Pelvic incidence was correlated with L1S1 lordosis,
      T1 sagittal offset and pelvic tilt. In OI patients, the T1T12 thoracic kyphosis
      was statistically higher than in control group and was not correlated with other
      shape (LL) or pelvic (SS, PT or PI) parameters. Because isolated T1T12 kyphosis
      increase without T4T12 significant modification, we suggest that vertebral
      deformations worsen in OI patients at the upper part of thoracic spine. Further
      studies are needed to precise the exact location of most frequent vertebral
      deformities.

PMID- 18820953
TI  - Aprotinin in pediatric neuromuscular scoliosis surgery.
AB  - Reduction of blood transfusions in patients with neuromuscular scoliosis can
      decrease potential complications such as immune suppression, infection, hemolytic
      reaction and viral transmission. Aprotinin (Trasylol), Bayer), an
      antifibrinolytic, has proven to be effective in reducing blood loss in cardiac
      and liver surgery, but little data exists in patients undergoing spinal fusion
      for neuromuscular scoliosis. The purpose of this study was to evaluate the safety
      and efficacy of aprotinin in pediatric neuromuscular scoliosis patients
      undergoing spinal fusion. The medical records of all patients undergoing initial
      spinal fusions for neuromuscular scoliosis between January 1999 and March 2003
      were reviewed to determine demographic data, perioperative data, wound drainage
      and number of transfusion required. Cases were compared to a matched group of
      historical controls. We had 14 patients in the aprotinin group and 17 in the
      control group. Total blood loss in the aprotinin group was significantly lower
      compared to the control group (715 vs. 2,110 ml; P = 0.007). Significantly less
      blood loss occurred in the aprotinin group when blood loss per kilogram was
      evaluated as well (23 vs. 60 ml/kg, respectively; P = 0.002). Intra-operative
      packed red blood cell (PRBC) transfusions were also significantly lower in the
      aprotinin group (1.25 vs. 3.16 units; P = 0.001). No clinical evidence of
      anaphylaxis, deep vein thrombosis (DVT) or renal failure was observed in the
      aprotinin group. After considering the price of drug therapy, operating room
      time, and the cost of blood products, the use of aprotinin saved an average of
      $8,577 per patient. In our series, the use of aprotinin resulted in decreased
      blood loss and a decreased rate of transfusions in children with neuromuscular
      scoliosis undergoing extensive spinal fusion. At out institution, the use of
      aprotinin is safe and cost effective for patients with neuromuscular scoliosis.

PMID- 18820954
TI  - Giant cell ependymoma of the cervical spinal cord: case report and review of the
      literature.
AB  - Ependymomas account for 2-6% of all central nervous system neoplasms. They
      develop from the ependymal cells that line the ventricular cavities of the brain
      and the central canal of the spinal cord, as well as from ependymal clusters in
      the filum terminale. Giant cell ependymoma (GCE) is a rare subtype, with few
      cases reported, mostly in the brain. We describe the case of a cervical spinal
      cord ependymoma with pleomorphic giant cells and focal calcifications occurring
      in a 25-year-old woman. Magnetic resonance imaging revealed a large multicystic
      and partially enhancing intramedullary tumour extending from C2 to C5.
      Intraoperative analysis of frozen section tissue fragments suggested a malignant
      tumour; however, an obvious cleavage plane was present around most of the mass,
      and a macroscopically complete tumour removal could be achieved. Subsequently,
      paraffin sections and immunohistochemical investigations revealed unequivocal
      evidence of a GCE with focal calcifications. This case, the second giant-cell
      ependymoma to be described in the spinal cord and the first with focal
      calcifications, highlights the features of GCE and the discrepancy between the
      worrisome histological appearance, the surgical findings and the clinical
      relatively good prognosis.

PMID- 18820955
TI  - Whiplash injuries: diagnosis and early management. The Swedish Society of
      Medicine and the Whiplash Commission Medical Task Force.

PMID- 18820956
TI  - Short anterior instrumented fusion and posterior convex non-instrumented fusion
      of hemivertebra for congenital scoliosis in very young children.
AB  - A variety of treatments has been described in the literature for the treatment of
      HV. We report the results of early surgical anterior instrumented fusion with
      partial preservation of the HV and posterior non-instrumented fusion in the
      treatment of progressive congenital scoliosis in children below the age of six.
      Between 1996 and 2006, 31 consecutive patients with 33 lateral HV and progressive
      scoliosis underwent short segment fusions. Mean age at surgery was 2 years and 10
      months. Mean follow-up period was 6.1 years. The major scoliotic curve improved
      from 41 degrees preoperatively to 17 degrees on follow-up. Preoperative segmental
      Cobb angle averaging 39 degrees was corrected to 15 degrees after surgery, being
      15 degrees at the last follow-up (62% of improvement). Compensatory cranial and
      caudal curves corrected by 47 and 45%, respectively. The angle of segmental
      kyphosis averaged 16 degrees before surgery, 11 degrees after surgery, and 11
      degrees at follow-up. There were two wound infections requiring surgical
      debridment, one intraoperative fracture of the vertebral body and one case lost
      correction due to implant failure. All went on to stable bony union. There were
      no neurological complications. Early diagnosis and early and aggressive surgical
      treatment are mandatory for a successful treatment of congenital scoliosis and
      prevention of the development of secondary compensatory deformities. Anterior
      instrumentation is a safe and effective technique capable of transmitting a high
      amount of convex compression allowing short segment fusion, which is of great
      importance in the growing spine.

PMID- 18820957
TI  - Autogenous auricular cartilage graft in temporomandibular joint ankylosis--an
      evaluation.
AB  - PURPOSE: Recurrence is a major problem after release of temporomandibular joint
      (TMJ) ankylosis. The purpose of this study was to evaluate the use of autogenous
      auricular cartilage graft as an interposition material after arthroplasty for TMJ
      ankylosis. MATERIALS AND METHODS: Ten patients (M = 4; F = 6) with TMJ ankylosis
      were treated with autogenous auricular cartilage graft interposition
      arthroplasty. Minimal follow-up was 2 years. The possible reasons for ankylosis
      and pre- and postoperative mouth opening at final follow-up were recorded.
      RESULTS: There was a single case of bilateral ankylosis, and a total of 11 joints
      were operated. The cause of ankylosis could be traced to trauma (n = 7) and ear
      infection (n = 3). The ages at operation ranged from 6 to 23 years. Postoperative
      mouth opening was satisfactory in all patients except one in whom relapse
      occurred. No donor site deformity was observed in any of the patients.
      CONCLUSION: Autogenous auricular cartilage graft is a good interposition material
      for successful treatment of TMJ ankylosis.

PMID- 18820958
TI  - Intramedullary lesions of the conus medullaris: differential diagnosis and
      surgical management.
AB  - The medullary conus represents a distinct entity of the spinal cord regarding its
      anatomical, clinical and microsurgical features. An overview of the pathologic
      processes of this region is provided. Epidemiological, clinical and
      neuroradiological characteristics of neoplastic (glial tumors, non-glial tumors,
      metastasis, primary melanomas) and non-neoplastic lesions (granulomatous lesions,
      abscess, parasitic infections, vascular, demyelinating and dysembryogenetic
      lesions) are discussed. Main MR imaging characteristics used to differentiate
      neoplastic from non-neoplastic lesions consist in pathological spinal cord
      expansion, gadolinium-enhancement and tumoural cyst formation. Management
      strategies differ substantially, depending on the kind of lesion. According to
      the suspected pathological entity radical resection, biopsy or conservative
      treatments are reasonable options. Intraoperative electrophysiological monitoring
      is a fundamental part of the surgical setting.

PMID- 18820959
TI  - Microvascular decompression as a surgical management for trigeminal neuralgia:
      long-term follow-up and review of the literature.
AB  - This retrospective study summarizes our experience based on treating 62 patients
      with trigeminal neuralgia treated with microvascular decompression. All patients
      had typical trigeminal neuralgia symptoms, with 24 of them (38%) having failed to
      benefit from other previous treatment paradigms. We excluded subjects with
      atypical and/or secondary forms of trigeminal neuralgia. Follow-up duration
      ranged from 5 months to 10 years 6 months, with recurrence being identified in
      three patients (4.8%).We found that the superior cerebellar artery is the leading
      offending vessel in our cases (33.9%; 21 patients). Interestingly, seven patients
      (11.3%) underwent an early reoperation 12-48 h later after the first operation
      was deemed ineffective. This subgroup recovered satisfactorily following
      isolation of the pathogenic vessels. Overall, no mortality was observed in our
      patients, and the only permanent morbidity outcome was a case of facial nerve
      palsy (1.6%). We conclude that microvascular decompression and its reapplicaiton
      for patients who showed no pain relief immediately after the first decompression
      are safe and effective treatments for trigeminal neuralgia.

PMID- 18820961
TI  - Abstracts of the 46th ISCEV (International Society for Clinical Electrophysiology
      of Vision) International Symposium. Morgantown, West Virginia, USA. July 10-15,
      2008.

PMID- 18820960
TI  - Characterisation of aerobically grown non-spore-forming bacteria from paper mill
      pulps containing recycled fibres.
AB  - A total of 179 non-spore-forming bacteria aerobically growing on Nutrient Agar,
      Plate Count Agar or in specific enrichment conditions for salmonella,
      campylobacteria, listeria, yersinia or staphylococci, were isolated from 16
      untreated paper mill pulps. After phenotypical screening the isolates were
      characterised by automated ribotyping and partial sequencing of the 16S rRNA
      gene. They could be divided into seven taxonomical classes representing 63 taxa
      (species): actinobacteria (11 species), bacilli (7), flavobacteria (3)
      alphaproteobacteria (10), betaproteobacteria (5), gammaproteobacteria (25) and
      sphingobacteria (2). Most of the gammaproteobacteria were enterobacteria, mainly
      species of the genera Enterobacter (7 species, 7 samples/3 mills) and Klebsiella
      (5 species, 6 samples/3 mills). Other commonly occurring bacteria were most
      closely related to Microbacterium barkeri (7 samples/3 mills), Cloacibacterium
      normanense (6 samples/2 mills), Pseudoxanthomonas taiwanensis (5 samples/2 mills)
      and Sphingobacterium composti (5 samples/1 mill). Sporadic isolates of Listeria
      innocua, L. monocytogenes, Enterococcus casseliflavus and Staphylococcus warneri
      were detected, from which only L. monocytogenes is considered to be a food
      pathogen. No isolates of the genera Campylobacter, Salmonella or Yersinia were
      detected. The detected bacteria may be harmful in process control, but the load
      of food pathogens with recycled fibres to paper machines is insignificant. Faecal
      contamination of the pulp samples was not indicated.

PMID- 18820962
TI  - Fracture healing in mice deficient in plasminogen activator inhibitor-1.
AB  - To evaluate the role of plasminogen activator inhibitor (PAI)-1, a key negative
      regulator of the plasmin system of extracellular matrix proteases in
      developmental bone growth and fracture repair, the bone phenotype of male adult
      PAI-1-deficient mice was determined and femoral fracture healing was compared
      with that of age- and sex-matched wild-type C57BL/6J control mice. Regarding bone
      phenotype, the length and size (but not cortical thickness) of the femur of male
      PAI-1-deficient mice were smaller than those of wild-type controls. Although the
      total bone mineral content of PAI-1-deficient mice was not significantly
      different from that of wild-type mice, the total bone area in PAI-1-deficient
      mice was smaller, leading to an increase in total bone mineral density. With
      respect to fracture healing, PAI-1-deficient mice developed fracture calluses
      that were larger and more mineralized than those of wild-type mice but only at 14
      days postfracture. These changes were even greater given the smaller size of the
      normal femur in PAI-1-deficient mice. Surprisingly, the larger fracture callus
      remodeled rapidly to normal size and mineral content by 21 days postfracture.
      Examination of fracture histology revealed that these changes were associated
      with a dramatic increase followed by a rapid remodeling of the fracture callus
      cartilage. The remodeling of fracture callus cartilage in PAI-1-deficient mice
      also displayed an abnormal pattern. These findings demonstrate for the first time
      that PAI-1 (and potentially the plasminogen extracellular matrix protease system)
      is an important regulator of bone size during developmental growth and plays a
      regulatory role in the determination of fracture callus size, cartilage
      formation, and resorption during bone fracture repair.

PMID- 18820963
TI  - Aesthetic/Cosmetic surgery and ethical challenges.
AB  - Is aesthetic surgery a business guided by market structures aimed primarily at
      material gain and profit or a surgical intervention intended to benefit patients
      and an integral part of the health-care system? Is it a frivolous subspecialty or
      does it provide a real and much needed service to a wide range of patients? At
      present, cosmetic surgery is passing through an identity crisis as well as an
      acute ethical dilemma. A closer look from an ethical viewpoint makes clear that
      the doctor who offers aesthetic interventions faces many serious ethical problems
      which have to do with the identity of the surgeon as a healer. Aesthetic surgery
      that works only according to market categories runs the risk of losing the view
      for the real need of patients and will be nothing else than a part of a beauty
      industry which has the only aim to sell something, not to help people. Such an
      aesthetic surgery is losing sight of real values and makes profit from the
      ideology of a society that serves only vanity, youthfulness, and personal
      success. Unfortunately, some colleagues brag that they chose the plastic surgery
      specialty just to become rich aesthetic surgeons, using marketing tactics to
      promote their practice. This is, at present, the image we project. As rightly
      proposed, going back a little to Hippocrates, to the basics of being a physician,
      is urgently warranted! Being a physician is all that a "cosmetic" surgeon should
      be. In the long run, how one skillfully and ethically practices the art of
      plastic surgery will always speak louder than any words.

PMID- 18820964
TI  - Endovascular treatment of arteriovenous malformation.
AB  - Vascular anomalies are common congenital or neonatal abnormalities. According to
      the approved classification of vascular lesions by Glowacki and Mulliken,
      hemangiomas and vascular malformations are distinguishable. Hemangiomas usually
      appear during the first days or weeks after birth and grow faster than the whole
      body of the infant. They are proliferating benign tumors that often involute. The
      opposite of hemangiomas, vascular malformations are present at birth, grow
      commensurately with the patient, demonstrate normal endothelial turnover, and
      never involute. The case of a young woman with an arteriovenous malformation
      (AVM) located on the left side of her face beneath the lower lip is described.
      The patient did not have any specific complaints except the cosmetic effect,
      which was a reddish and bluish discoloration of the skin over the lesion. The AVM
      was embolized with polyvinyl alcohol, and no subsequent surgery was performed.
      Follow-up ultrasound examination after a 12-month period showed no flow within
      the lesion area.

PMID- 18820965
TI  - Arcus marginalis release II via endoscopic midface-lift.
AB  - Tear troughs in combination with midfacial ptosis may be early and synergistic
      signs of aging. Premaxillary and suborbicularis oculi fat (SOOF) descent
      decreases soft tissue volume covering the orbital rim, while prolapsing
      retroseptal fat actually underscores the resulting tear trough shadow. This
      volume change precedes skin redundancy. Thus, volume redistribution avoiding
      external skin incisions is the adequate treatment. De la Plaza's
      transconjunctival lower lid blepharoplasty is a reliable tool for arcus
      marginalis release. For patients also requiring an endoscopic midface-lift, even
      the transconjunctival incision for intraorbital fat compartment realignment can
      be avoided by performing the release of the lower orbita septum via the buccal
      mucosa incision.

PMID- 18820966
TI  - Assessing local knowledge use in agroforestry management with cognitive maps.
AB  - Small-holder farmers often develop adaptable agroforestry management techniques
      to improve and diversify crop production. In the cocoa growing region of Ghana,
      local knowledge on such farm management holds a noteworthy role in the overall
      farm development. The documentation and analysis of such knowledge use in cocoa
      agroforests may afford an applicable framework to determine mechanisms driving
      farmer preference and indicators in farm management. This study employed 12 in
      depth farmer interviews regarding variables in farm management as a unit of
      analysis and utilized cognitive mapping as a qualitative method of analysis. Our
      objectives were (1) to illustrate and describe agroforestry management variables
      and associated farm practices, (2) to determine the scope of decision making of
      individual farmers, and (3) to investigate the suitability of cognitive mapping
      as a tool for assessing local knowledge use. Results from the cognitive maps
      revealed an average of 16 +/- 3 variables and 19 +/- 3 links between management
      variables in the farmer cognitive maps. Farmer use of advantageous ecological
      processes was highly central to farm management (48% of all variables),
      particularly manipulation of organic matter, shade and food crop establishment,
      and maintenance of a tree stratum as the most common, highly linked variables.
      Over 85% of variables included bidirectional arrows, interpreted as farm
      management practices dominated by controllable factors, insofar as farmers
      indicated an ability to alter most farm characteristics. Local knowledge use on
      cocoa production revealed detailed indicators for site evaluation, thus affecting
      farm preparation and management. Our findings suggest that amid multisourced
      information under conditions of uncertainty, strategies for adaptable
      agroforestry management should integrate existing and localized management
      frameworks and that cognitive mapping provides a tool-based approach to advance
      such a management support system.

PMID- 18820967
TI  - Improvement of raw sausage fermentation by stress-conditioning of the starter
      organism Lactobacillus sakei.
AB  - Effective growth and high acidification activity during meat fermentation are key
      characteristics of starter lactobacilli to ensure hygienic safety and sensory
      quality of the product. In this study, we demonstrated that the performance of
      Lactobacillus sakei in sausage fermentation can be improved by preinoculation
      treatments with sublethal heat, cold, and salt stress. Sausages were produced and
      inoculated with stress-treated cells of L. sakei 23 K (pLPV111) and the isogenic
      mutant of the class III heat-shock repressor CtsR, which was previously shown to
      exhibit improved growth in fermenting sausages. The pH values of sausages
      fermented with stressed cells attained defined threshold values in a distinctly
      shorter time than those inoculated with unstressed cells. In particular, the cold
      stressed cells (4 degrees C) reduced the pH to 5.0 within approximately 40 hours
      compared with approximately 70 hours for untreated cells. This enhanced
      acidification activity of the cold-stressed cells was consistent with an
      increased growth rate. Growth studies in culture medium showed that stress
      treated cells with improved performance did not exhibit this advantage when
      exposed to curing salt, one of the major stressors at the beginning of sausage
      fermentation. Preinoculation stress treatment is a promising way to improve the
      effectiveness of meat starter lactobacilli.

PMID- 18820968
TI  - Regulation of the spoVM gene of Bacillus subtilis.
AB  - The spoVM gene of Bacillus subtilis codes for a 26 amino-acid peptide that is
      essential for sporulation. Analysis of the expression of the spoVM gene revealed
      that wild-type cells started to synthesize a spoVM-specific transcript at t2,
      whereas the SpoVM peptide accumulated at t4. Both the transcript and the peptide
      were absent from an spoVM knockout strain. The 5' untranslated region of the
      spoVM transcript increased expression of SpoVM. Possible regulation mechanisms
      are discussed.

PMID- 18820969
TI  - Cellulose biosynthesis by the beta-proteobacterium, Chromobacterium violaceum.
AB  - The Chromobacterium violaceum ATCC 12472 genome was sequenced by The Brazilian
      National Genome Project Consortium. Previous annotation reported the presence of
      cellulose biosynthesis genes in that genome. Analysis of these genes showed that,
      as observed in other bacteria, they are organized in two operons. In the present
      work, experimental evidences of the presence of cellulose in the extracellular
      matrix of the biofilm produced by C. violaceum in static cultures are shown.
      Biofilm samples were enzymatically digested by cellulase, releasing glucose
      units, suggesting the presence of cellulose as an extracellular matrix component.
      Fluorescence microscopy observations showed that C. violaceum produces a
      cellulase-sensitive extracellular matrix composed of fibers able to bind
      calcofluor. C. violaceum grows on medium containing Congo red, forming brown-red
      colonies. Together, these results suggest that cellulase-susceptible matrix
      material is cellulose. Scanning electronic microscopy analysis showed that the
      extracellular matrix exhibited a network of microfibrils, typical of bacterial
      cellulose. Although cellulose production is widely distributed between several
      bacterial species, including at least the groups of Gram-negative proteobacteria
      alpha and gamma, we give for the first time experimental evidence for cellulose
      production in beta-proteobacteria.

PMID- 18820970
TI  - The luxS gene is involved in AI-2 production, pathogenicity, and some phenotypes
      in Erwinia amylovora.
AB  - Erwinia amylovora causes fire blight of apple, pear, and other members of the
      Rosaceae family. The enzyme LuxS catalyzes the last step in the production of
      autoinducer-2 (AI-2), a molecule implicated with quorum sensing in many bacterial
      species. It is now well recognized that LuxS also plays a central role in sulfur
      metabolism and in the activated methyl cycle, which is responsible for the
      generation of S-adenosyl-L-methionine. A research paper has reported that luxS is
      not involved with quorum sensing in Er. amylovora, but in our study, Er.
      amylovora strain NCPPB1665 (Ea1665) produced luxS-dependent extracellular AI-2
      activity. Additionally, the maximal AI-2 activity occurred during late
      exponential and early-stationary growth phases and diminished during the
      stationary phase. The luxS mutant of Ea1665 was constructed, and the phenotypes
      of a defined luxS mutant have been characterized. Inactivation of luxS in Ea1665
      impaired motility, extracellular polysaccharide (EPS) production, and tolerance
      for hydrogen peroxide, and reduced virulence on pear leaves.

PMID- 18820972
TI  - Letter in response to Ihedioha U, Mackay G, Leung E, Molloy RG, O'Dwyer PJ (2007)
      Laparoscopic colorectal resection does not reduce incisional hernia rates when
      compared with open colorectal resection. Surg Endosc 22:689-692.

PMID- 18820973
TI  - Results after conservative treatment of serous borderline tumors of the ovary
      with a micropapillary pattern.
AB  - OBJECTIVE: The aim of this study was to assess the outcomes of patients treated
      conservatively for a serous borderline ovarian tumor with micropapillary patterns
      (SBOT-MP). METHODS: Retrospective study collecting cases of conservative
      treatment of SBOT-MP. There are 15 patients treated with conservative management
      for a stage I (n = 8) or III (n = 7) SBOT-MP. Eight patients underwent a
      unilateral salpingo-oophorectomy with a contralateral cystectomy, three a
      unilateral salpingo-oophorectomy, two a cystectomy, and two a bilateral
      cystectomy. Four patients had stromal microinvasion associated with MP at
      histological examination of the ovarian tumor. Noninvasive implants were observed
      in eight patients and invasive implants in one. Three patients had residual
      disease <1 cm on the peritoneum. One patient received adjuvant chemotherapy.
      RESULTS: After a median interval of 63 months (range, 18-120 months), 11
      recurrences were observed: six of them exclusively on the ovary, three
      exclusively on the peritoneum (invasive peritoneal disease in one), and two on
      the ovary and peritoneum. One of the last two patients succumbed to the
      recurrence (under the form of invasive adenocarcinoma). The other patients were
      actually disease free. Five patients achieved eight spontaneous pregnancies.
      CONCLUSION: This study demonstrates that spontaneous pregnancies can be achieved
      after conservative treatment of SBOT-MP. Nevertheless, as 2/3 of patients had
      bilateral ovarian involvement at the time of initial management, the recurrence
      rate is high. However, making definitive conclusions about the safety of
      conservative surgery is limited by the small sample size. So, further studies are
      warranted to evaluate conservative management of advanced-stage disease.

PMID- 18820974
TI  - Feasibility of sentinel lymph node biopsy through an inframammary incision for a
      nipple-sparing mastectomy.
AB  - BACKGROUND: Nipple-sparing mastectomy (NSM) via an inframammary (IM) incision has
      been described for selected patients with breast cancer. However, the application
      of sentinel lymph node (SLN) mapping via an IM incision for NSM has yet to be
      reported. The objective of this study is to determine the technical feasibility
      of performing SLN through an IM incision without making an axillary
      counterincision. METHODS: We retrospectively reviewed our single-institutional
      experience with SLN biopsy and NSM through IM incisions between January 2006 and
      March 2008. Clinicopathologic factors were analyzed regarding indications,
      technical details, postoperative morbidity, and follow-up. RESULTS: Fifty-two
      patients underwent 87 NSM through an IM incision (17 unilateral, 35 bilateral)
      with immediate reconstruction and SLN biopsy. Indications for surgery included
      invasive breast cancer (n = 21), ductal carcinoma in situ (DCIS) (n = 18), and
      prophylactic (n = 48). Mean tumor size of invasive carcinoma was 2.1 cm. The mean
      mastectomy specimen weight was 437 g. Subareolar injection consisted of blue dye
      (n = 43), technetium sulfur colloid (n = 2), or combination injection (n = 42).
      SLN biopsy through an IM incision was successfully performed in 84 of 87 cases
      (96.6%). A mean of 2.8 SLN were removed with a positive sentinel node encountered
      in 8 of 21 patients (38%) with invasive cancer. No complications were observed
      regarding the SLN portion of the operation. With a median follow-up of 6.5 months
      (range, 0.4-23 months), there have been no axillary local recurrences.
      CONCLUSION: SLN biopsy can be performed through an IM incision during a NSM,
      avoiding a secondary axillary incision.

PMID- 18820975
TI  - Surveys, quality cancer care, and evidence-based medicine: embracing care
      delivery drivers.

PMID- 18820976
TI  - Arthroscopic hemitrapeziectomy for first carpometacarpal arthritis: results at 7
      year follow-up.
AB  - The purpose of this study was to determine the outcome of arthroscopic
      hemitrapeziectomy combined with thermal capsular plication and temporary K-wire
      fixation in patients with painful thumb basal joint due to either osteoarthritis
      or posttraumatic arthritis. There were 18 thumbs that were evaluated in this
      retrospective study of arthroscopic hemitrapeziectomy of the distal trapezium in
      addition to a pancapsular thermal shrinkage at an average of 7.6-year follow-up.
      No patient has required further surgery. A subjective improvement in pain, pinch
      activities, strength, and range of motion (ROM) was noted in all patients, and no
      patient had further surgery on their thumb. On exam, no patient had a first
      carpal-metacarpal grind or laxity. Total ROM of the thumb axis decreased by 20%,
      but all patients could oppose to the fifth finger. Grip strength remained
      unchanged, key pinch improved from 8 to 11 lbs, and tip pinch improved from 4 to
      5 lbs. Radiographs showed a metacarpal subsidence of 1.8 mm (0-4 mm). Four
      complications were noted: two cases of dorsal radial nerve neuritis, one rupture
      of the flexor pollicis longus, and one prolonged hematoma. Results demonstrate
      that arthroscopic hemitrapeziectomy and capsular shrinkage for first
      carpometacarpal arthritis is an effective technique that provides high patient
      satisfaction, a functional pain-free thumb, and a reliable rate of return to
      activity.

PMID- 18820977
TI  - Single-blinded randomized trial of mechanical bowel preparation for colon surgery
      with primary intraperitoneal anastomosis.
AB  - INTRODUCTION: We report the final analysis of a prospective single-blinded
      randomized trial designed to investigate whether omission of preoperative
      mechanical bowel preparation increases the rate of surgical-site infection and
      anastomotic failure after elective colon surgery with intraperitoneal anastomosis
      by a single surgeon. PATIENTS AND METHODS: Patients scheduled to undergo an
      elective colon or proximal rectal resection with a primary anastomosis by a
      single surgeon were randomized to receive either oral polyethylene glycol (Group
      A) or no mechanical bowel preparation (Group B). Patients were followed by an
      independent surgeon. RESULTS: One hundred and forty nine patients were enrolled.
      Three patients (2%) were preoperatively excluded because of active
      immunosuppression and 13 (9%) were excluded from the final analysis. Of the
      remaining 129 patients, 65 were assigned to Group A and 64 to Group B. Thirty
      patients (23.2%) developed wound infection, (Group A = 24.6% and Group B = 17.2%;
      NS). There were three cases of intra-abdominal sepsis a (Group A 4.6%). The
      anastomotic failure rate was 5.4% (n = 7), four patients in Group A (6.2%) vs.
      three patients in Group B (4.7%) (NS). When SSI and anastomotic failure were
      combined, the complication rate in Group A was 35.4% vs. 21.9% for Group B. The
      NNH was 7.4. CONCLUSION: Our final analysis shows that a single surgeon will not
      have a higher rate of either surgical-site infection or anastomotic failure if
      he/she routinely omits preoperative mechanical bowel preparation.

PMID- 18820979
TI  - Percutaneous endoscopic gastrostomy tube insertion via gastro-gastric fistula in
      a gastric bypass patient.
AB  - Enteral feedings are the preferred route of nutritional support for malnourished
      or critically ill patients. Recent progress in flexible endoscopic and
      interventional radiological techniques has allowed adaptation of numerous new
      procedures. Anatomic and functional rearrangement of the gastrointestinal tract
      often precludes traditional percutaneus endoscopic gastrostomy tube placement.
      Insertion of a gastroscope through the nose, via open pharynx, or neck fistula
      have been described, but there are no reports in the English literature
      describing introduction of the gastroscope through a dilated gastro-gastric
      fistula in a patient with previous open Roux en Y gastric bypass.

PMID- 18820978
TI  - Do Incretins play a role in the remission of type 2 diabetes after gastric bypass
      surgery: What are the evidence?
AB  - Gastric bypass surgery (GBP), in addition to weight loss, results in dramatic
      remission of type 2 diabetes (T2DM). The mechanisms by which this remission
      occurs are unclear. Besides weight loss and caloric restriction, the changes in
      gut hormones that occur after GBP are increasingly gaining recognition as key
      players in glucose control. Incretins are gut peptides that stimulate insulin
      secretion postprandially; the levels of these hormones, particularly glucagon
      like peptide-1, increase after GBP in response to nutrient stimulation. Whether
      these changes are causal to changes in glucose homeostasis remain to be
      determined. The purpose of this review is to assess the evidence on incretin
      changes and T2DM remission after GBP, and the possible mechanisms by which these
      changes occur. Our goals are to provide a thorough update on this field of
      research so that recommendations for future research and criteria for bariatric
      surgery can be evaluated.

PMID- 18820980
TI  - Elevated concentrations of liver enzymes and ferritin identify a new phenotype of
      insulin resistance: effect of weight loss after gastric banding.
AB  - BACKGROUND: Several studies have associated elevated liver enzymes (LFTs),
      obesity, and type 2 diabetes (T2DM), and a link has been established between
      insulin resistance (IR) and elevated ferritin concentrations. We examined the
      relationship between LFTs, ferritin, and IR in morbid obese subjects and the
      effect of weight loss after bariatric surgery. METHODS: We measured liver
      enzymes, ferritin, insulin resistance, and glucose tolerance (by OGTT) in 159
      morbid obese subjects (BMI = 44.4 +/- 0.4 kg/m(2)) at baseline, 6 months and 1
      year after laparoscopic-adjustable-gastric banding (LAGB). Subjects were divided
      in two groups: increased LFTs (ALT > 30; AST/ALT < 1) vs. normal LFTs. RESULTS: A
      large proportion of morbid obese subjects had increased LFTs (44%) which were
      associated with increased IR and ferritin, suggesting potential liver disease. A
      majority of the morbidly obese with increased LFTs, IGT, and T2DM, were male and
      had almost double ferritin concentrations, strongly correlated with ALT (r =
      0.43, p < 0.0001). Both ferritin and ALT correlated with waist circumference and
      IR. One year after, LAGB glucose tolerance improved, LFTs and IR were reduced;
      ferritin did not change significantly, but was still correlated with IR.
      CONCLUSIONS: Ferritin may be an additional useful marker for more severe hepatic
      IR.

PMID- 18820981
TI  - The female knee: anatomic variations and the female-specific total knee design.
AB  - The concept and need for a gender-specific or female-specific total knee
      prosthesis have generated interest and discussion in the orthopaedic community
      and the general public. This concept relies on the assumption of a need for such
      a design and the opinion that there are major anatomic differences between male
      and female knees. Most of the information regarding this subject has been
      disseminated through print and Internet advertisements, and through direct-to
      patient television and magazine promotions. These sources and a recent article in
      a peer-reviewed journal, which support the need for a female-specific implant
      design, have proposed three gender-based anatomic differences: (1) an increased Q
      angle, (2) less prominence of the anterior medial and anterior lateral femoral
      condyles, and (3) reduced medial-lateral to anterior-posterior femoral condylar
      aspect ratio. We examined the peer-reviewed literature to determine whether women
      have had worse results than men after traditional TKAs. We found women have equal
      or better results than men. In addition, we reviewed the evidence presented to
      support these three anatomic differences. We conclude the first two proposed
      differences do not exist, and the third is so small that it likely has no
      clinical effect. LEVEL OF EVIDENCE: Level IV, systematic review. See the
      Guidelines for Authors for a complete description of levels of evidence.

PMID- 18820982
TI  - Is radiation superior to indomethacin to prevent heterotopic ossification in
      acetabular fractures?: a systematic review.
AB  - Heterotopic ossification is a well-known complication after fixation of an
      acetabular fracture. Indomethacin and radiation therapy are used as prophylaxis
      to prevent heterotopic ossification. It is unclear, however, whether either is
      superior, although this may relate to lack of power in individual studies. To
      compare the effectiveness of indomethacin with the effectiveness of radiation
      therapy, we conducted a systematic review in which all published prospective
      studies were evaluated. We performed a literature search in PubMed, MEDLINE,
      EMBASE, and the Cochrane Controlled Trial Register. The retrieved studies were
      analyzed and categorized according to the quality and validity score of Jadad et
      al. We found five appropriate prospective studies, describing 384 patients.
      Although the quality of the available studies made a proper meta-analysis
      inappropriate, the incidence of heterotopic ossification was significantly lower
      in patients treated with radiation than in patients receiving indomethacin (five
      of 160 versus 20 of 224, respectively). Until further information is available,
      we believe the evidence supports radiation therapy as the preferred method for
      preventing heterotopic ossification after operative treatment of acetabular
      fractures. LEVEL OF EVIDENCE: Level II, therapeutic study. See the Guidelines for
      Authors for a complete description of levels of evidence.

PMID- 18820983
TI  - Proximal humerus reconstructions for tumors.
AB  - The optimal method for reconstructing the proximal humerus in patients with
      tumors is controversial. To determine functional outcomes and complication rates
      after different types of reconstructions, we reviewed a consecutive series of 49
      patients who underwent proximal humerus resection and osteoarticular allograft
      (17 patients), allograft-prosthetic composite (16), or endoprosthetic (16)
      reconstruction. Operative indications included primary malignancies (24
      patients), metastatic disease (19), and benign aggressive disease (six). Implant
      revision was more common after osteoarticular reconstruction (five of 17) than
      after allograft-prosthetic composite (one of 16) or endoprosthetic (zero of 16)
      reconstructions. At a minimum followup of 24 months (median, 98 months; range, 24
      214 months) in surviving patients, Musculoskeletal Tumor Society functional
      scores averaged 79% for the allograft-prosthetic composite, 71% for the
      osteoarticular allograft, and 69% for the endoprosthetic reconstruction cohorts.
      Shoulder instability was associated with abductor mechanism compromise and was
      more common after endoprosthetic reconstruction. Allograft fractures occurred in
      53% of patients receiving osteoarticular allografts. We recommend allograft
      prosthetic composite reconstruction for younger patients with primary tumors of
      bone and endoprosthetic reconstruction for older patients with metastatic
      disease. Because of the unacceptable complication rate, we do not recommend
      osteoarticular allograft reconstruction for routine use in the proximal humerus.
      LEVEL OF EVIDENCE: Level III, therapeutic study. See the Guidelines for Authors
      for a complete description of levels of evidence.

PMID- 18820984
TI  - Case reports: fractures of threaded cups: rare complications of a well
      established implant.
AB  - The use of cementless threaded cups in THA is a well-established treatment.
      Fractures of the cups are rare complications recorded in individual cases with
      material defects being discussed as the primary cause. We analyzed three cases of
      fractured cups. Although all three cups were well fixed to existing bone, we
      observed deficient osseous backing dorsocranially and abrasion particles. There
      were no signs of femoroacetabular impingement or infection. The cups showed
      corrosion debris. Scanning electron microscopic investigations showed
      characteristics of fretting and fretting-related corrosion. We concluded the
      fractures occurred because of fretting combined with inadequate bony support
      leading to fatigue of the material and subsequent fracture.

PMID- 18820986
TI  - The classic: On the means of lengthening, in the lower limbs, the muscles and
      tissues which are shortened through deformity. 1905.

PMID- 18820985
TI  - Can the volume of pelvic osteolysis be calculated without using computed
      tomography?
AB  - The most common method to diagnose and monitor osteolysis is the standard
      anteroposterior radiograph. Unfortunately, plain radiographs underestimate the
      incidence and extent of osteolysis. CT scans are more sensitive and accurate but
      also more expensive and subject patients to more radiation. To determine whether
      the volume of pelvic osteolysis could be accurately estimated without a CT scan,
      we evaluated the relationships between CT volume measurements and other variables
      that may be related to the size of pelvic osteolytic lesions in 78 THAs. Only the
      area of pelvic osteolysis measured on radiographs, heavy patient activity level,
      and total volume of wear were associated with the pelvic osteolysis volume
      measured on CT in the context of the multivariate regression analysis. Despite a
      strong correlation (r = 0.93, r(2) = 0.87) between these three variables and the
      volume of pelvic osteolysis measured on CT, estimates of pelvic osteolysis volume
      deviated from the actual volume measured on CT by more than 10 cm(3) among eight
      of the 78 THAs in this study. CT images remain our preferred modality when
      accurate assessments of pelvic osteolysis volume are required. LEVEL OF EVIDENCE:
      Level III, diagnostic study. See Guidelines for Authors for a complete
      description of levels of evidence.

PMID- 18820987
TI  - Correlation of shear to compression for progressive fracture obliquity.
AB  - The accompanying shear force at the point of bone opposition is an important
      factor inherent to tibial fracture stability during axial loading. We determined
      at which angle of fracture obliquity shearing becomes a dominant force after
      stabilization with circular external fixation, and how modifications to the
      external fixator can reduce this effect. We constructed tibial fracture models
      with a successively increasing fracture angle obliquely (from 0 degrees to 60
      degrees) to determine the stability in the classic Ilizarov frame and subsequent
      frame modifications during axial loading (maximum, 1000 N). Stability was
      determined by measuring the fracture line displacement for each fracture
      obliquity model after an applied axial load. Fracture line displacement was
      recorded as coordinate component changes as measured by an ultrasonic digitizer.
      We defined construct stability as less than 2 mm of fracture line migration with
      loading. More than 3500 data points were collected for this study. The classic
      Ilizarov construct successfully stabilized fractures with up to 30 degrees of
      fracture obliquity, after which divergent instability occurs. The addition of
      proximal and distal perpendicular half-pins provides little benefit. Arced wires
      provided stability up to 40 degrees fracture obliquity. A formal steerage pin
      construct provided stability for all fracture models (up to 60 degrees of
      fracture obliquity) with all applied loads (up to 1000-N axial load).

PMID- 18820988
TI  - DEXA as a predictor of fixator removal in distraction osteogenesis.
AB  - Premature removal of the fixator after a lengthening procedure can result in
      gradual bending or acute fracture of the regenerate. We reviewed the records of
      26 patients who underwent 28 limb lengthenings between 1997 and 2005 to assess
      the post lengthening regenerate fracture rate and bone healing index when using
      dual energy xray absorptiometry (DEXA) to aid in deciding on when to remove the
      fixator. Sixteen male and 10 female patients with an average age at lengthening
      of 12.3 years underwent an average lengthening of 5.2 cm (range, 3-9.1 cm).
      Nineteen femurs and nine tibiae were lengthened. Serial monthly DEXA scans were
      analyzed for bone mineral density. Bone healing indices and post fixator removal
      complications were assessed. The fixators were removed once the bone mineral
      density had plateaued to a less than 10% increase and plain radiographs showed no
      obvious defects precluding fixator removal. There were no regenerate fractures
      and only one fracture in the proximal segment of the lengthened bone after
      apparatus removal and the healing index for the series averaged 47 d/cm (range,
      20-73 d/cm). Using serial DEXA scans during the consolidation phase of
      lengthening has a low rate (3.6%) of fractures while maintaining an acceptable
      bone healing index without excessively increasing fixation time. LEVEL OF
      EVIDENCE: Level IV, therapeutic retrospective study. See the Guidelines for
      Authors for a complete description of levels of evidence.

PMID- 18820989
TI  - Effects of vitamin D insufficiency on bone mineral density in African American
      men.
AB  - In African American men serum, 25-hydroxyvitamin D (25-OHD) was below 30 ng/ml in
      89% of subjects. In overall group, there was no correlation between 25-OHD and
      bone mineral density (BMD). A subgroup analysis of subjects with 25-OHD <or=15
      ng/ml showed that serum 25-OHD was positively associated with BMD. INTRODUCTION:
      This study examined the effects of low serum 25-hydroxyvitamin D (25-OHD) on bone
      mineral density (BMD) in African American (AA) men from the general medicine
      clinic at an inner city Veteran Administration medical center. METHODS: The data
      for 112 AA males who had both 25-OHD levels and BMD of spine and hip were
      extracted and analyzed using SAS software. RESULTS: AA men were aged 38 to 85
      years, with mean age of 62 years. Levels of 25-OHD ranged from 4 to 45 ng/ml,
      with mean 17.5 ng/ml, 24% and 89% of the subjects had 25-OHD below 10 and 30
      ng/ml, respectively. In the overall group, there was no correlation between 25
      OHD and BMD at any site. In a subgroup analysis of subjects with 25-OHD <or=15
      ng/ml, in multiple adjusted models, 25-OHD was positively associated with BMD of
      spine (r = 0.26, p = 0.05), total hip (r = 0.27, p < 0.05), ward's triangle (r =
      0.25, p = 0.05), and trochanter (r = 0.30, p < 0.05). CONCLUSIONS: The negative
      effect of vitamin D insufficiency on bone was observed only at very low levels of
      25-OHD, suggesting that AA male skeleton is relatively resistant to the effects
      of secondary hyperparathyroidism.

PMID- 18820990
TI  - Severe abdominal injuries sustained in an adult wearing a pelvic seatbelt: a case
      report and review of the literature.
AB  - In automobile accidents, the "seatbelt syndrome" (SBS) consists of a
      constellation of injuries, predominantly involving thoraco-lumbar vertebral
      fractures and intraabdominal organ injury. A recent amendment to Irish
      legislation has made the wearing of seatbelts mandatory for all rear seated
      passengers in an effort to protect children. Whilst rear seatbelts result in a
      significant reduction in morbidity and mortality following road traffic accidents
      (RTA), we present a case in which the rear lap seatbelt caused severe abdominal
      injuries. It is evident that the current rear seat lapbelt system is an inferior
      design associated with a significant morbidity and mortality when compared to
      three-point harness system and consideration should be given to replacing them in
      all motor vehicles.

PMID- 18820991
TI  - Gossypiboma: a case report and review of the literature.
AB  - INTRODUCTION: Post-operative complications in surgery may frequently be
      unavoidable. However, some complications result from human error, both in the
      intra-operative and post-operative period. One such complication, which is
      frequently underreported, is the retained swab, or gossypiboma. CASE REPORT: We
      report a case from our hospital of a patient who presented with unexplained
      pyrexia, 4 years post-gynaecological surgery in another institution. A 67-year
      old woman from overseas presented to our emergency department with a 2-day
      history of pyrexia, collapse and confusion. Following a CT guided biopsy, which
      was inconclusive, she was scheduled for retroperitoneal biopsy. In theatre, a
      retained swab was discovered. CONCLUSION: Prevention of gossypiboma is far better
      than cure. Strict adherence to swab counts, and the avoidance of change of staff
      during procedures is important in decreasing the incidence. Perhaps, with the
      increasing use of minimally invasive procedures, the incidence of gossypiboma
      will fall dramatically.

PMID- 18820992
TI  - Carotid artery stenting: findings based on 8 years' experience.
AB  - PURPOSE: Carotid artery stenting (CAS) may be an alternative to surgical
      endarterectomy not only in high-risk patients. Few data are available regarding
      the long-term clinical efficacy of CAS with the use of cerebral protection
      devices and the incidence of restenosis. Our experience demonstrates that if
      certain requirements are fulfilled, CAS can be considered a safe and effective
      treatment with high short-and long-term success rates. MATERIALS AND METHODS: In
      the past 8 years, we treated 1,003 patients (1,096 arteries) affected by internal
      carotid artery stenosis, 93 with bilateral stenosis. Of these, 567 (51.74%) were
      symptomatic and 529 (48.26%) asymptomatic lesions. The preprocedural evaluation
      was performed with Doppler ultrasound (US), magnetic resonance (MR)
      angiography/computed tomography (CT) angiography and a neurological evaluation.
      Antiplatelet therapy was administered before and after the procedure. RESULTS:
      Technical success was achieved in 1,092 cases (99.6%), and a cerebral protection
      device was successfully used in 1,019 procedures (92.9%). The 30-day transient
      ischaemic attack (TIA)/stroke/death rate was 2.16%: death (0.18%) major stroke
      (0.45%) and minor stroke/TIA (1.53%). During a follow-up up to 8 years,
      restenoses occurred in 39 cases (3.57%), of which 28 were post-CAS (2.57%) and 11
      post-CAS performed for restenosis after carotid endarterectomy (1%). Only five
      symptomatic restenoses>80% were treated with a repeated endovascular procedure.
      CONCLUSIONS: A retrospective analysis of our experience suggests that CAS is a
      safe and effective procedure with better results than endarterectomy. In up to 8
      years of follow-up, CAS seems to be effective in preventing stroke, with a low
      restenosis rate.

PMID- 18820993
TI  - Power Doppler ultrasonography with time-signal intensity curves in monitoring
      hepatocellular carcinoma and liver metastases after intralesional therapy.
AB  - PURPOSE: Analysis of time-intensity curves allows evaluation of the patterns of
      lesion enhancement before and after treatment. The aim of this study was to
      evaluate the diagnostic accuracy of time-intensity curves in monitoring
      intralesional therapy of focal hepatic lesions. MATERIALS AND METHODS: Twenty
      patients underwent intralesional therapy with either radiofrequency thermal
      ablation or percutaneous ethanol injection. Contrast-enhanced power Doppler
      ultrasound with analysis of time-intensity curves was performed one day before
      and one day after treatment. Targeted biopsy was then obtained to confirm the
      imaging findings. RESULTS: Before treatment, all lesions showed time-intensity
      curves characterised by high peaks of signal intensity and plateaus. Complete
      tumour necrosis, confirmed by targeted biopsy, was observed in patients showing
      no intralesional flow signals and time-intensity curves with low peak of signal
      intensity and absence of plateau after treatment. Biopsy confirmed the presence
      of residual neoplastic tissue in one patient exhibiting perilesional vascularity,
      absence of intralesional flow signals, and a time-intensity curve with high peak
      of signal intensity and plateau. CONCLUSIONS: According to our findings, time
      intensity curves characterised by high peak of signal intensity and plateau might
      reflect the presence of perilesional or intralesional neoplastic tissue and
      provide important information on the effectiveness of the treatment.

PMID- 18820994
TI  - D-Aspartate affects secretory activity in rat Harderian gland: molecular
      mechanism and functional significance.
AB  - In this paper, the role of D-aspartate in the rat Harderian gland (HG) was
      investigated by histochemical, ultrastructural, and biochemical analyses. In this
      gland, substantial amounts of endogenous D-Asp were detected, along with
      aspartate racemases that convert D-Asp to L-Asp and vice versa. We found that the
      gland was capable of uptaking and accumulating exogenously administered D-Asp. D
      Asp acute treatment markedly increased lipid and porphyrin secretion and induced
      a powerful hyperaemia in inter-acinar interstitial tissue. Since D-Asp is known
      to be recognized by NMDA receptors, the expression of such receptors in rat HG
      led us to the hypothesis that D-Asp acute treatment induced the activation of the
      extracellular signal-regulated protein kinase (ERK) and nitric oxide synthase
      (NOS) pathways mediated by NMDA. Interestingly, as a result of enhanced oxidative
      stress due to increased porphyrin secretion, the revealed activation of the
      stress-activated protein kinase/c-jun N-terminal kinase (SAPK/JNK) pro-apoptotic
      pathway was probably triggered by the gland itself to preserve its cellular
      integrity.

PMID- 18820995
TI  - Refractory anemia with ringed sideroblasts associated with thrombocytosis:
      comparative analysis of marked with non-marked thrombocytosis, and relationship
      with JAK2 V617F mutational status.
AB  - The World Health Organization (WHO) classification of tumors of hematopoietic and
      lymphoid tissues (2001) defined a provisional entity named refractory anemia with
      ringed sideroblasts associated to marked thrombocytosis (RARS-MT). Diagnosis of
      RARS-MT requires more than 15% of ringed sideroblasts in bone marrow aspirate and
      the existence of a thrombocytosis in blood, with a platelet count above 600 x
      10(9)/L. Nevertheless, controversy exists regarding this platelet count "cut-off"
      value and, when RARS-MT was defined, the JAK2 mutation and its importance in the
      study of myeloproliferative disorders was unknown. We present the results of a
      Spanish retrospective multicentric study, which includes 76 cases of RARS with
      associated thrombocytosis (platelet count above 400 x 10(9)/L) at diagnosis (RARS
      T), 36 of them with a platelet count above 600 x 10(9)/L. Our aim was to analyze
      their clinical, analytical and morphological characteristics, and to establish
      correlations with the JAK2 mutational status.

PMID- 18820996
TI  - Biological and potential therapeutic roles of sirtuin deacetylases.
AB  - Sirtuins comprise a unique class of nicotinamide adenine dinucleotide (NAD(+))
      dependent deacetylases that target multiple protein substrates to execute diverse
      biological functions. These enzymes are key regulators of clinically important
      cellular and organismal processes, including metabolism, cell division and aging.
      The desire to understand the important determinants of human health and lifespan
      has resulted in a firestorm of work on the seven mammalian sirtuins in less than
      a decade. The implication of sirtuins in medically important areas such as
      diabetes, cancer, cardiovascular dysfunction and neurodegenerative disease has
      further catapulted them to a prominent status as potential targets for
      nutritional and therapeutic development. Here, we present a review of published
      results on sirtuin biology and its relevance to human disease.

PMID- 18820997
TI  - A celebration of wine: wine IS medicine.
AB  - Wine describes a diverse commodity class composed of the yeast fermentation
      products of the must, or juice, pressed from grapes, the fruit of genus Vitis,
      but both in animal and human studies, wine demonstrates beneficial properties
      that are independent from the presence of alcohol. These benefits for health are
      mostly associated with polyphenols, and are absorbable from wine but poorly from
      unfermented grape juice. Dealcoholised wine is providing all the benefits without
      the toxicity, and is very affordable; improvements in the organoleptic quality of
      dealcoholised wine(s) as well as massive distribution are current challenges.

PMID- 18820998
TI  - Transport mechanisms of carnosine in SKPT cells: contribution of apical and
      basolateral membrane transporters.
AB  - PURPOSE: The aim of this study was to investigate the transport properties of
      carnosine in kidney using SKPT cell cultures as a model of proximal tubular
      transport, and to isolate the functional activities of renal apical and
      basolateral transporters in this process. METHODS: The membrane transport
      kinetics of 10 microM [3H]carnosine was studied in SKPT cells as a function of
      time, pH, potential inhibitors and substrate concentration. A cellular
      compartment model was constructed in which the influx, efflux and transepithelial
      clearances of carnosine were determined. Peptide transporter expression was
      probed by RT-PCR. RESULTS: Carnosine uptake was 15-fold greater from the apical
      than basolateral surface of SKPT cells. However, the apical-to-basolateral
      transepithelial transport of carnosine was severely rate-limited by its cellular
      efflux across the basolateral membrane. The high-affinity, proton-dependence,
      concentration-dependence and inhibitor specificity of carnosine supports the
      contention that PEPT2 is responsible for its apical uptake. In contrast, the
      basolateral transporter is saturable, inhibited by PEPT2 substrates but non
      concentrative, thereby, suggesting a facilitative carrier. CONCLUSIONS: Carnosine
      is expected to have a substantial cellular accumulation in kidney but minimal
      tubular reabsorption in blood because of its high influx clearance across apical
      membranes by PEPT2 and very low efflux clearance across basolateral membranes.

PMID- 18820999
TI  - Anion binding mediated precipitation of a peptibody.
AB  - PURPOSE: Understand the underlying mechanism governing the salt-induced
      precipitation of a basic (pI = 8.8) protein, Peptibody A (PbA), in acidic
      solutions. METHODS: The rate, extent, and reversibility of PbA precipitation was
      monitored over 4-weeks as a function of pH (3.7-5.0), salt concentration (0-400
      mM), and ion identity using a series of monovalent, Hofmeister anions (F(-), Cl(
      ), Br(-), I(-), ClO(4) (-), SCN(-)) and cations (Li+, Na+, K+, Rb+, Cs+). The
      effects of salt on conformational stability and reduced valence were determined
      using Fourier-transform infrared spectroscopy, circular dichroism, and capillary
      electrophoresis/analytical ultracentrifugation. RESULTS: PbA precipitation
      occurred upon salt addition and could be modulated with solution pH, salt
      identity & concentration. The precipitation was sensitive to anions, but not
      cations, and increased with anion size. A reverse Hofmeister effect (SCN(-)
      approximately ClO(4) (-)>I(-)>Cl(-)>Br(-)>F(-)) was observed with "salting-in"
      anions being the more effective precipitants. An increase in the precipitation
      rate below pH 4.3 indicated that protonation of aspartyl and glutamyl side-chains
      was also important for precipitation. The reversibility of precipitation was
      excellent (100%) at 4 degrees C but decreased upon storage at 25 degrees C and 37
      degrees C; the loss in reversibility correlated with an increase in
      intermolecular beta-sheet content of the precipitate. CONCLUSION: Salts, employed
      as buffering, tonicifying, and viscosity modifying agents, may adversely affect
      the solubility of basic proteins formulated under acidic conditions.

PMID- 18821000
TI  - Celebremos la Salud: a community-based intervention for Hispanic and non-Hispanic
      white women living in a rural area.
AB  - The evaluation for Celebremos La Salud, a community randomized trial of Hispanic
      cancer prevention found no differences in mammography screening rates between
      intervention and control communities. The goal of the present study was to
      determine reasons for the intervention's lack of effectiveness. In the first aim,
      we assessed reach of the intervention. In the second, we assessed which
      intervention activities were associated with mammography use. In the third, we
      examined whether factors related to health care access, education level, or age
      modified the effect of the intervention. Data were used from a post-intervention
      survey of 20 rural communities in Washington State. Hispanic (N = 202) and non
      Hispanic White (N = 389) women, over age 40 formed the sample. Reporting having
      awareness of or having participated in intervention activities was positively
      associated with Hispanic ethnicity and intervention group and negatively
      associated with lack of health insurance and having a lower education level. Only
      one intervention activity was associated with screening use. Having participated
      in presentations at organizations was positively associated with having had a
      mammogram in the previous 2 years for Hispanic women. No individual level
      modifiers influenced the intervention's effectiveness. Heavily targeting the
      intervention to Hispanic women and not reaching as many White women may have
      contributed to the lack of intervention effect. Increasing mammography screening
      rates among women living in a rural area may require improved access to health
      care and reaching women with lower education levels and lack of health insurance.

PMID- 18821001
TI  - Association between media alerts of air quality index and change of outdoor
      activity among adult asthma in six states, BRFSS, 2005.
AB  - Media alerts of air quality index (AQI) were designed to inform the public the
      need to avoid harmful air pollution by changing their outdoor activities. The
      relationship between AQI media alerts and change in outdoor activities among
      people with asthma is unknown. Our objective is to examine this relationship.
      Data were analyzed in a cross-sectional study from 33,888 adults, in six states,
      who responded to the questions in the 2005 Behavioral Risk Factor Surveillance
      System (BRFSS) about reductions/changes in outdoor activity. The prevalence of
      change in outdoor activity due to media alerts was 31% among adults with lifetime
      asthma and 16% without asthma. The prevalence of outdoor activity change
      increased to 75% among those with lifetime asthma and to 68% without asthma, when
      the combined the effects of media alerts and individual perception were examined.
      The odds of activity change based on the media alerts was 2.30 (Adjusted odds
      ratio [aOR] = 2.16, 95% Confidence interval [CI]: 1.61, 2.90) among those with
      lifetime asthma and 1.72 (aO R = 1.72, 95% CI: 1.50, 1.98) without asthma,
      compared to those unaware of media alerts, after adjustment for demographic
      variables and covariates. This study shows that awareness of media alerts as well
      as health professional advice may be associated with reported changes in outdoor
      activities. Therefore, along with consistent efforts to improve the air quality,
      government agencies, health professionals, and community leaders should implement
      measures to effectively inform the public about air quality and educate them to
      take appropriate actions accordingly.

PMID- 18821002
TI  - Outcome evaluation of a 3-year senior health and wellness initiative.
AB  - The Wilmington Senior Center developed a 3-year multidisciplinary health and
      wellness initiative entitled The Time of Your Life to promote healthy aging for
      participants attending countywide senior centers. The purpose of this paper is to
      describe the development and implementation of the evaluation methodology and
      outcomes of this senior health and wellness project that consisted of 11 programs
      in total. Long-term programming can present several challenges in both
      implementation and evaluation, but assessing outcomes is critical to documenting
      program value and accountability. Participant-completed surveys and post-series
      focus groups were utilized as the evaluation tools. Our findings indicate that
      the program's objectives of increasing knowledge and motivating adoption or
      maintenance of a healthy lifestyle were met to varying degrees, while a third
      objective of assessing the usefulness of resources to inform health-related
      decisions was unable to be evaluated due to the cross-sectional nature of the
      data collection. Post-series focus groups indicated that topics of most interest
      to seniors were money management, medications and staying mentally and physically
      fit. The evaluations showed that long-term programming, while challenging, can be
      a successful and sustainable format for senior health education.

PMID- 18821003
TI  - Knowledge about breastfeeding among a group of primary care physicians and
      residents in Puerto Rico.
AB  - Physicians have an essential role in promoting, protecting, and supporting
      breastfeeding as the ideal method of infant feeding. They are in an important
      position to promote breastfeeding but report difficulty in advising mothers with
      lactation problems. The purpose of this study is to assess knowledge about
      breastfeeding among primary care physicians and residents and identify potential
      barriers to its promotion. One hundred seventy-seven residents and physicians
      answered an anonymous questionnaire. The participants recognized breastfeeding
      benefits but 26% did not encourage exclusive breastfeeding. Mastitis, breast
      abscess, and the use of medications by the mother were considered
      contraindications to breastfeeding. Temporary breastfeeding discontinuation and
      bilirubin levels measurement were the preferred recommendations for the jaundiced
      infant. Most physicians received training in breastfeeding benefits although they
      report fair knowledge in myths, techniques, and contraindications. Physicians
      demonstrated to recognize breastfeeding benefits, but formal education is needed
      to eliminate barriers to breastfeeding promotion and support.

PMID- 18821004
TI  - Effects antifreeze peptides on the thermotropic properties of a model membrane.
AB  - In this paper, we report on the effect of short segments of type I antifreeze
      protein (AFP I) on the thermotropic properties of a model membrane. Two different
      types of dimyristoylphosphatidylcholine model membranes were used, multilamellar
      vesicles and small unilamellar vesicles. The membrane properties were studied by
      differential scanning calorimetry (DSC) and fluorescence anisotropy. With the
      incorporation of AFP I and its short segments, the order of the model membrane
      increased both in the gel state and in the liquid crystalline state. The
      interaction of AFPs with the model membrane caused a shift in the phase
      transition to lower temperatures, which is accompanied by a broadening of the DSC
      thermogram. This preferential stabilization to a more ordered phase by the AFPs
      could be due to ordering the hydrophobic membrane core and separation into
      domains. Overall, this approach of employing short segments of AFP I simplifies
      the correlation between antifreeze protein characteristics and the effect of
      these parameters on the interaction mechanism of AFP with cell membranes. The
      success of this approach can lead to the identification of short peptides with
      high antifreeze activity.

PMID- 18821005
TI  - Susceptibility of current adaptive behavior measures to feigned deficits.
AB  - The current study examined the susceptibility of the Adaptive Behavior Assessment
      System-2nd edition (ABAS-II; Harrison & Oakland, 2003) and the Scales of
      Independent Behavior-Revised (S1B-R; Bruininks, Woodcock, Weatherman, & Hill,
      1996) to the feigning of adaptive functioning deficits. Using four different
      instruction sets, the authors evaluated whether the provision of diagnostic
      information (a form of coaching) improved participants' ability to simulate
      adaptive deficits commensurate with a diagnosis of mental retardation. The
      authors found that the ABAS-II was quite vulnerable to believable manipulation by
      raters, while the SIB-R was not. In fact, exaggeration on the SIB-R was easily
      detected regardless of the information provided. Implications regarding the use
      of these measures in Atkins mental retardation evaluations are discussed.

PMID- 18821006
TI  - Advances in remote monitoring of implantable pacemakers, cardioverter
      defibrillators and cardiac resynchronization therapy systems.
AB  - Unlike the standard quarterly or semi-annual direct ambulatory device
      interrogations procedures, state-of-the-art implantable electronic cardiovascular
      devices (IECD) enable their wireless remote interrogation and monitoring, and
      automatically send reports and special alerts on a daily basis. This allows
      physicians to respond more proactively to changes in patient or device status,
      more appropriately triage patient care, and more efficiently perform the post
      implant ambulatory follow-ups. This review presents the-state-of the-art
      technology of remote IECD monitoring and summarizes the main clinical
      observations published through June 2008. Cardiovascular remote monitoring
      systems made by several manufacturers are currently in various phases of
      development, clinical investigation, and medical applications. Data collected in
      several completed and ongoing studies strongly suggest that this new technology
      will make important contributions, particularly with respect to the facilitation
      of IECD follow-ups, enhancement of patient safety and quality of life, and
      lowering of medical costs. Further technological advances and a more clear
      understanding and appreciation of the clinical and economic benefits of
      telecardiology, will likely increase sharply the use of remote IECD monitoring in
      upcoming years.

PMID- 18821007
TI  - Evaluation of 3D guided electroanatomic mapping for ablation of atrial
      fibrillation in reference to CT-Scan image integration.
AB  - BACKGROUND: Anatomical guided atrial fibrillation (AF) catheter ablation relies
      on the assumption that the left atrium reconstruction anatomy (LARA) using a 3D
      mapping system precisely matches the patient's CT scan anatomy (real anatomy).
      This study investigates whether this postulation is accurate using CT scan image
      integration. PATIENTS AND METHODS: Thirty consecutive patients (23 men, mean age
      = 51.9 +/- 9.9 years) with symptomatic drug-refractory paroxysmal (n = 21) or
      persistent (n = 9) AF underwent a circumferential, 2 x 2, pulmonary vein (PV)
      radiofrequency (RF) ablation using the CARTOMERGE system. Left atrium (LA)
      anatomy was first reconstructed and RF design lines drawn on this LARA. After a
      CT-scan image of the LA was integrated into the 3D system, RF lesions were
      deployed 10 +/- 5 mm outside the PV ostia (PVO) onto the CT-scan LA surface. The
      match between the actual RF lines and the RF design lines was analyzed off-line
      after catheter withdrawal. RESULTS: Circumferential RF design lines were divided
      into four segments encircling both the right and left PVs. Design segments
      matched the actual RF segments in a proportion varying from 23% up to 83%. A mean
      of 2.8 +/- 1.6 segments per patient were inaccurately designed that extended a
      mean of 3.8 +/- 2.3mm inside the adjacent PV or 6.7 +/- 1.8mm inside the left
      atrial appendage (LAA). Seven patients (23%) had four or more segments
      incorrectly designed. CONCLUSIONS: Our study reveals the inaccuracy of 3D
      anatomic guided RF ablation with respect to the LA anatomical structures that
      could be possibly improved when combined with CT-scan image integration.

PMID- 18821008
TI  - GABA(A) receptor downregulation in brains of subjects with autism.
AB  - Gamma-aminobutyric acid A (GABA(A)) receptors are ligand-gated ion channels
      responsible for mediation of fast inhibitory action of GABA in the brain.
      Preliminary reports have demonstrated altered expression of GABA receptors in the
      brains of subjects with autism suggesting GABA/glutamate system dysregulation. We
      investigated the expression of four GABA(A) receptor subunits and observed
      significant reductions in GABRA1, GABRA2, GABRA3, and GABRB3 in parietal cortex
      (Brodmann's Area 40 (BA40)), while GABRA1 and GABRB3 were significantly altered
      in cerebellum, and GABRA1 was significantly altered in superior frontal cortex
      (BA9). The presence of seizure disorder did not have a significant impact on
      GABA(A) receptor subunit expression in the three brain areas. Our results
      demonstrate that GABA(A) receptors are reduced in three brain regions that have
      previously been implicated in the pathogenesis of autism, suggesting widespread
      GABAergic dysfunction in the brains of subjects with autism.

PMID- 18821009
TI  - Dynamic alterations of cerebral pial microcirculation during experimental
      subarachnoid hemorrhage.
AB  - The study aimed to investigate the involvement of cerebral microcirculation
      turbulence after subarachnoid hemorrhage (SAH). Wistar rats were divided into non
      SAH and SAH groups. Autologous arterial hemolysate was injected into rat's
      cisterna magna to induce SAH. Changes of pial microcirculation within 2 h were
      observed. It was found that there were no obvious changes of the diameters, flow
      velocity, and fluid state of microvessels in non-SAH group. With the exception of
      rare linear-granular flow in A4 arteriole, linear flow was observed in most of
      the arterioles. There was no blood agglutination in any of the arterioles. After
      SAH, abnormal cerebral pial microcirculation was found. Spasm of microvessels,
      decreased blood flow, and agglutination of red blood cells occurred. Five minutes
      following the induction of SAH, the diameters of the arterioles and venules
      significantly decreased. The decreased diameters persisted for 2 h after
      cisternal injection. Decreased flow velocity of venules was found from 5 to 90
      min after induction of SAH. Spasm of the basilar artery and increased brain
      malondialdehyde were also found after SAH. We concluded that cerebral
      microcirculation turbulence plays an important role in the development of
      secondary cerebral ischemia following SAH.

PMID- 18821010
TI  - Interaction between syntaxin 8 and HECTd3, a HECT domain ligase.
AB  - Ubiquitination of proteins and their degradation within the proteasome has
      emerged as the major proteolytic mechanism used by mammalian cells to regulate
      cytosolic and nuclear protein levels. Substrate ubiquitylation is mediated by
      ubiquitin (Ub) ligases, also called E3 Ub ligases. HECT-E3 Ub ligases are
      characterized by the presence of a C-terminal HECT domain that contains the
      active site for Ub transfer onto substrates. Among the many E3 Ub ligases, the
      family homologous to E6-Ap C-terminus (HECT) E3 Ub ligases, which includes the
      yeast protein Rsp5p and the mammalian homolog NEDD4, AIP4/Itch, and Smurf, has
      been shown to ubiquitylate membrane proteins and, in some instances, to induce
      their degradation. In this report, we have identified Syntaxin 8 as a binding
      protein to a novel HECT domain protein, HECT domain containing 3 (HECTd3), by
      yeast two-hybrid screen. Besides HECT domain, HECTd3 contains an anaphase
      promoting complex, subunit 10 (APC10) domain. Our co-immunoprecipitation
      experiments show that Syntaxin 8 directly interacts with HECTd3 and that the
      overexpression of HECTd3 promotes the ubiquitination of Syntaxin 8.
      Immunofluorescence results show that Syntaxin 8 and HECTd3 have similar
      subcellular localization.

PMID- 18821011
TI  - Founder mutations account for the majority of BRCA1-attributable hereditary
      breast/ovarian cancer cases in a population from Tuscany, Central Italy.
AB  - BACKGROUND: Germline mutations in the BRCA1 and BRCA2 tumour-suppressor genes
      predispose to early-onset breast and ovarian cancer. Although both genes display
      a highly heterogeneous mutation spectrum, a number of alterations recur in some
      populations. Only a limited number of founder mutations have been identified in
      the Italian population so far. OBJECTIVE: To investigate the spectrum of
      BRCA1/BRCA2 mutations in a set of families originary from the Central-Eastern
      part of Tuscany and to ascertain the presence of founder effects. We also wanted
      to approximate the age of the most frequent BRCA1 founder mutation. RESULTS:
      Overall, four distinct BRCA1 mutations accounted for a large fraction (72.7%) of
      BRCA1-attributable hereditary breast/ovarian cancer in families originary from
      this area. We identified common haplotypes for two newly recognised recurrent
      BRCA1 mutations, c.3228_3229delAG and c.3285delA. The c.3228_3229delAG mutation
      was estimated to have originated about 129 generations ago. Interestingly, male
      breast cancer cases were present in 3 out of 11 families with the
      c.3228_3229delAG mutation. CONCLUSIONS: The observation that a high proportion of
      families with BRCA1 alterations from Central-Eastern Tuscany harbours a limited
      number of founder mutations can have significant impact on clinical management of
      at risk subjects from this area. In addition, the identification of a large set
      of families carrying an identical mutation that predisposes to breast and ovarian
      cancer provides unique opportunities to study the effect of other genetic and
      environmental factors on penetrance and disease phenotype.

PMID- 18821012
TI  - The 76-gene signature defines high-risk patients that benefit from adjuvant
      tamoxifen therapy.
AB  - PURPOSE: To assess the benefit from adjuvant systemic tamoxifen therapy in breast
      cancer risk groups identified by the previously established prognostic 76-gene
      signature. METHODS: In 300 lymph node-negative (LNN), estrogen receptor-positive
      (ER+) breast cancer patients (136 treated with adjuvant tamoxifen, 164 having
      received no systemic adjuvant therapy), distant metastasis-free survival (DMFS)
      as a function of the 76-gene signature was determined in a multicenter fashion.
      RESULTS: In 136 tamoxifen-treated patients, the 76-gene signature identified a
      group of patients with a poor prognosis [hazard ratio (HR), 4.62; P = 0.0248].
      These patients showed a 12.3% absolute benefit of tamoxifen in 10-year DMFS (HR,
      0.52; P = 0.0318) compared with untreated high-risk patients. This represented a
      71% increase in relative benefit compared with the 7.2% absolute benefit observed
      for all 300 patients without using the gene signature. In the low-risk group
      there was no significant 10-year DMFS benefit of tamoxifen. CONCLUSIONS: The 76
      gene signature defines high-risk patients who benefit from adjuvant tamoxifen
      therapy. Although we did not study the value of chemotherapy in this study, low
      risk patients identified by the 76-gene signature have a prognosis good enough
      that chemotherapy would be difficult to justify. The prognosis of these patients
      is sufficiently good, in fact, that a disease-free benefit for tamoxifen therapy
      is difficult to prove, though benefits in terms of loco-regional relapse and a
      reduction in risk for contralateral breast cancer might justify hormonal therapy
      in these patients.

PMID- 18821013
TI  - Nothing for something? Estimating cost and value for beneficiaries from recent
      medicare spending increases on HMO payments and drug benefits.
AB  - The Medicare Modernization Act of 2003 added a new outpatient prescription drug
      benefit to Medicare and increased payments to HMOs. We estimate a nested logit
      model of plan choice to quantify the welfare benefits from these two expansion
      paths. We find that the addition of stand-alone prescription drug plans was
      welfare improving and produced nine times as much value per government dollar as
      the increase in payments to HMOs. In light of these results, we suggest that HMO
      bidding procedures should be modified to reduce payments to HMOs by about $67
      billion over the next 10 years.

PMID- 18821014
TI  - Fabrication of protein chips based on 3-aminopropyltriethoxysilane as a
      monolayer.
AB  - Although 3-aminopropyltriethoxysilane (APTES) is widely adopted as a monolayer in
      biosensors, experimental silanization takes at least 1 h at high temperature.
      Therefore, the feasibility of the silanization with APTES in a short reaction
      time and at room temperature was investigated. The surface modification of glass
      slides using a self-assembled monolayer of APTES with a concentration of 10% was
      studied by immobilizing FITC. APTES was successfully immobilized on the glass
      slide. The effect of reaction temperature and time of silanization were
      investigated. Various silanization conditions of APTES were examined by contact
      angle measurement and fluorescence microscopy. The surface of glass patterns with
      a gold thin film as background was characterized by determining the fluorescent
      intensities following the immobilization of fluorescein isothiocyanate (FITC),
      protein A-FITC, antimouse IgG-FITC and sheep anti-bovine albumin-FITC. The
      normalized fluorescent intensity indicated that a short period (4 min) of
      silanization at 25 degrees C suffices to form an APTES thin film by the
      immobilization of protein A on a glass surface. Such a condition does not require
      microheaters and temperature sensors in a microfluidic system, which will
      significantly reduce the manufacturing process, cost, and reaction time in the
      future.

PMID- 18821015
TI  - Spreadable dispersion of insect sex pheromone capsules, preparation via complex
      coacervation and release control of the encapsulated pheromone component
      molecule.
AB  - Using insect female pheromone to disrupt their mating process is a new
      technology, which has been applied as environment friendly pesticides in
      agricultural and forestry industries to control pest infestation. Dodecanol
      (C(12)OH), as one of the simple pheromone component, was chosen and encapsulated
      as core material using gelatin (GE) and acacia gum (AG) as wall materials via
      complex coacervation. Through variations in capsule preparations, particularly
      the crosslinking density of the wall materials, release controllability of
      C(12)OH was studied. A series of C(12)OH-containing capsules were prepared with
      different concentrations of GE and AG and different crosslinkings. Crosslinking
      and C(12)OH encapsulation were enhanced when more crosslinker, either
      formaldehyde or glutaraldehyde, were used. At same level of crosslinker, lower
      crosslinking and higher C(12)OH encapsulation were obtained in microcapsules done
      with formaldehyde than those with glutaraldehyde. Constant release of C(12)OH was
      achieved in capsules prepared with glutaraldehyde. Mechanisms of C(12)OH release
      were discussed based on the results. Scanning electron microscopy was used to
      characterize the structure and morphology of the microcapsules, which seemingly
      confirmed existence of a core-shell structure in the capsules, with the
      coacervated polymers as the shell and C(12)OH the core.

PMID- 18821016
TI  - Effect of actuation sequence on flow rates of peristaltic micropumps with PZT
      actuators.
AB  - Many biomedical applications require the administration of drugs at a precise and
      preferably programmable rate. The flow rate generated by the peristaltic
      micropumps used in such applications depends on the actuation sequence.
      Accordingly, the current study performs an analytical and experimental
      investigation to determine the correlation between the dynamic response of the
      diaphragms in the micropump and the actuation sequence. A simple analytical model
      of a peristaltic micropump is established to analyze the shift in the resonant
      frequency of the diaphragms caused by the viscous damping effect. The analytical
      results show that this damping effect increases as the oscillation frequency of
      the diaphragm increases. A peristaltic micropump with three piezoelectric
      actuators is fabricated on a silicon substrate and is actuated using 2-, 3-, 4-
      and 6-phase actuation sequences via a driving system comprising a microprocessor
      and a phase controller. A series of experiments is conducted using de-ionized
      water as the working fluid to determine the diaphragm displacement and the flow
      rates induced by each of the different actuation sequences under phase
      frequencies ranging from 50 Hz to 1 MHz. The results show that the damping effect
      of actuation sequences influences diaphragm resonant frequency, which in turn
      affects the profiles of flow rates.

PMID- 18821017
TI  - Improving abortion access in Canada.
AB  - Though abortion is legal in Canada, policies currently in place at various levels
      of the health care system, and the individual actions of medical professionals,
      can inhibit access to abortion. This paper examines the various extra-legal
      barriers to abortion access that exist in Canada, and argues that these barriers
      are unjust because there are no good reasons for the restrictions on autonomy
      that they present. The paper then outlines the various policy measures that could
      be taken to improve access.

PMID- 18821019
TI  - Adrenal changes associated with adrenarche.
AB  - The mechanisms causing the rise in adrenal androgen production during the course
      of adrenarche remain to be defined. However, the increase in steroid release is
      clearly associated with a series of intra-adrenal changes in the expression of
      steroidogenic enzymes needed for dehydroepiandrosterone (DHEA) and
      dehydroepiandrosterone sulfate (DHEAS) production, as well as an expansion of the
      adrenal zona reticularis (ZR). We and others have defined the adrenal expression
      pattern of key steroidogenic enzymes during adrenarche. As adrenarche proceeds,
      the expanding ZR expresses greater levels of cytochrome b5 (CYB5) and steroid
      sulfotransferase (SULT2A1) than the adjacent fasciculata. In contrast, the
      growing ZR is deficient in 3beta-hydroxysteroid dehydrogenase type 2 (HSD3B2).
      The resulting profile of steroidogenic enzymes lends itself to the production of
      adrenal androgens and appears to track the progression of adrenarche. This
      article reviews the intra-adrenal changes of the adrenal cortex associated with
      adrenarche.

PMID- 18821020
TI  - Keeping up appearances: perceptions of street food safety in urban Kumasi, Ghana.
AB  - The growing street food sector in low-income countries offers easy access to
      inexpensive food as well as new job opportunities for urban residents. While this
      development is positive in many ways, it also presents new public health
      challenges for the urban population. Safe food hygiene is difficult to practice
      at street level, and outbreaks of diarrheal diseases have been linked to street
      food. This study investigates local perceptions of food safety among street food
      vendors and their consumers in Kumasi, Ghana in order to identify the most
      important aspects to be included in future public health interventions concerning
      street food safety. This qualitative study includes data from a triangulation of
      various qualitative methods. Observations at several markets and street food
      vending sites in Kumasi were performed. Fourteen street food vendors were chosen
      for in-depth studies, and extensive participant observations and several
      interviews were carried out with case vendors. In addition, street interviews and
      Focus Group Discussions were carried out with street food customers. The study
      found that although vendors and consumers demonstrated basic knowledge of food
      safety, the criteria did not emphasize basic hygiene practices such as hand
      washing, cleaning of utensils, washing of raw vegetables, and quality of
      ingredients. Instead, four main food selection criteria could be identified and
      were related to (1) aesthetic appearance of food and food stand, (2) appearance
      of the food vendor, (3) interpersonal trust in the vendor, and (4) consumers
      often chose to prioritize price and accessibility of food--not putting much
      stress on food safety. Hence, consumers relied on risk avoidance strategies by
      assessing neatness, appearance, and trustworthiness of vendor. Vendors were also
      found to emphasize appearance while vending and to ignore core food safety
      practices while preparing food. These findings are discussed in this paper using
      social and anthropological theoretical concepts such as 'purity',
      'contamination', 'hygiene puzzles', and 'impression behaviors' from Douglas, Van
      Der Geest, and Goffman. The findings indicate that educating vendors in safe food
      handling is evidently insufficient. Future public health interventions within the
      street food sector should give emphasis to the importance of appearance and
      neatness when designing communication strategies. Neglected aspects of food
      safety, such as good hand hygiene and cleanliness of kitchen facilities, should
      be emphasized. Local vendor networks can be an effective point of entry for
      future food hygiene promotion initiatives.

PMID- 18821018
TI  - Androgen synthesis in adrenarche.
AB  - The enzymes and pathways of steroidogenesis are central to an understanding of
      adrenarche. The quantitative regulation of steroidogenesis occurs at the first
      step, the conversion of cholesterol to pregnenolone. Chronic quantitative
      regulation is principally at the level of transcription of the CYP11A1 gene
      encoding P450scc, which is the enzymatically rate-limiting step. Acute regulation
      is mediated by the steroidogenic acute regulatory protein (StAR), which
      facilitates the rapid influx of cholesterol into mitochondria, where P450scc
      resides. Qualitative regulation, which determines the type of steroid produced in
      a cell, is principally at the level of P450c17 (CYP17). In the absence of P450c17
      in the zona glomerulosa, C21 deoxy steroids are produced, leading to the
      mineralocorticoid, aldosterone. In the presence of the 17alpha-hydroxylase but
      not the 17,20 lyase activity of P450c17 in the zona fasciculata, C21, 17-hydroxy
      steroids are produced, leading to the glucocorticoid, cortisol. When both the
      17alpha-hydroxylase and 17,20 lyase activities of P450c17 are present in the zona
      reticularis, the androgen precursor DHEA is produced. The discrimination between
      17alpha-hydroxylase and 17,20 lyase activities is regulated by two post
      translational events, the serine phosphorylation of P450c17 and the allosteric
      action of cytochrome b5, both of which act to optimize the interaction of P450c17
      with its obligatory electron donor, P450 oxidoreductase. In the adrenal zona
      reticularis, the abundant expression of P450 oxidoreductase and cytochrome b5,
      and the low expression of 3beta-hydroxysteroid dehydrogenase (HSD3B2) result in
      the production of the large amounts of DHEA that characterize adrenarche.

PMID- 18821021
TI  - Circulating fatty acids and prostate cancer risk in a nested case-control study:
      the Multiethnic Cohort.
AB  - OBJECTIVE: Dietary fat, including specific fatty acids, has been proposed to
      contribute to prostate cancer pathogenesis, but findings from the studies based
      on biomarkers have been conflicting. METHODS: We examined the association between
      erythrocyte membrane fatty acid composition and prostate cancer risk in a nested
      case-control study within a multiethnic cohort of African Americans, Native
      Hawaiians, Japanese Americans, Latinos, and Whites. Analyses included 376 cases
      and 729 matched controls. Conditional logistic regression was used to estimate
      the odds ratios and 95% confidence intervals with adjustment for multiple
      covariates. RESULTS: No significant association was found for saturated, mono-
      and polyunsaturated fatty acid, or for specific n-3 and n-6 fatty acids, even
      when the analysis was limited to advanced or high grade prostate cancer. In
      ethnic specific analyses, there was a positive association with palmitic acid in
      Japanese Americans that was significantly different from the null results in
      other groups. There was also an increased risk with n-3 fatty acids and the ratio
      of n-3/n-6 fatty acids in Whites. CONCLUSION: Although there was a suggestion of
      ethnic specific associations with some fatty acids, our overall findings do not
      support a role for fatty acids in prostate carcinogenesis.

PMID- 18821022
TI  - Monitoring conservation effectiveness in a global biodiversity hotspot: the
      contribution of land cover change assessment.
AB  - Tropical forests, which play critical roles in global biogeochemical cycles,
      radiation budgets and biodiversity, have undergone rapid changes in land cover in
      the last few decades. This study examines the complex process of land cover
      change in the biodiversity hotspot of Western Ghats, India, specifically
      investigating the effects of conservation measures within the Indira Gandhi
      Wildlife Sanctuary. Current vegetation patterns were mapped using an IRS P6 LISS
      III image and this was used together with Landsat MSS data from 1973 to map land
      cover transitions. Two major and divergent trends were observed. A dominant
      degradational trend can be attributed to agricultural expansion and
      infrastructure development while a successional trend, resulting from protection
      of the area, showed the resilience of the system after prolonged disturbances.
      The sanctuary appears susceptible to continuing disturbances under the current
      management regime but at lower rates than in surrounding unprotected areas. The
      study demonstrates that remotely sensed land cover assessments can have important
      contributions to monitoring land management strategies, understanding processes
      underpinning land use changes and helping to inform future conservation
      strategies.

PMID- 18821023
TI  - Mapping chlorophyll-a through in-situ measurements and Terra ASTER satellite
      data.
AB  - This paper presents an application of water quality mapping through real-time
      satellite and ground data. The Lake Beysehir which is the largest freshwater lake
      and drinking water reservoir in Turkey was selected as the study area. Terra
      ASTER satellite image is used as remote sensing data source for water quality
      mapping in addition to simultaneously performed in-situ measurements. Ground data
      is collected simultaneously with the ASTER overpass on June 09, 2005 over the
      Lake Beysehir. The spatial distribution map is developed by using multiple
      regression (MR) technique for water quality parameter, which is chlorophyll-a
      (chl-a). The results indicate that simultaneous ground and satellite remote
      sensing data are highly correlated (R (2) > 0.86). In the image processing step,
      geometric correction, image filtering and development of water quality map
      procedures are performed with the ERDAS Imagine and ArcGIS 9.0 software. The
      trophic status of Lake Beysehir is considered to be oligotrophic with an average
      1.55 microg/l chl-a concentration.

PMID- 18821024
TI  - Monitoring of the physical parameters and evaluation of the chemical composition
      of river and groundwater in Calabar (Southeastern Nigeria).
AB  - A 12-month study was carried to assess the seasonal and tidal effects on the
      physical parameters of river and groundwater, which constitute the major potable
      water sources in Calabar (Nigeria). The study also included an evaluation of the
      chemical composition of the different water bodies and their relationship. The
      results show that there was a significant seasonal effect on dissolved oxygen
      (DO) and nitrate in groundwater on one hand, and on temperature, redox potential
      (Eh), and DO in river water on the other. Also, a significant tidal influence
      exists on DO in both river-and groundwater. Comparison between groundwater and
      river water show statistically significant difference in EC, TDS, Eh, DO, Na, Cl
      and NO(3). The significant differences in EC, TDS, Na and Cl are due to tidal
      flushing. The difference in Eh is due to geology of the area while, NO(3) is as a
      result of anthropogenic pollution. The concentrations of ions in the river and
      groundwater for the different seasons and tidal cycles show an inverse
      relationship, while the river water is generally more concentrated than the
      groundwater. Using a binary mixing model, estimates show that the degree of
      mixing of river water and groundwater is low, with values of between 1.93% and
      2.76% respectively, in the western and eastern parts of the study area. The study
      concludes that tidal flushing, anthropogenic effects and oxygen supply during
      recharge contribute to the shaping of water chemistry in the area.

PMID- 18821025
TI  - Mercury fractionation in stream sediments from the Quadrilatero Ferrifero gold
      mining region, Minas Gerais State, Brazil.
AB  - The Iron Quadrangle (IQ) region, located in the state of Minas Gerais, has been
      the most important gold producing area in Brazil since the end of seventeenth
      century. The use of mercury for gold amalgamation in small scale mines has been
      responsible for large release of Hg to aquatic and terrestrial environments
      during 300 years of mining. The present work sought to evaluate the fractionation
      of Hg in stream sediments is the southern region of the IQ by utilizing
      sequential extraction. Since mobility and availability of Hg are related to its
      distribution among sediment partitions, fractionation methods provide detailed
      information on the ecotoxicological impact and risks associated to the presence
      of Hg in sediments. The total Hg concentration varied from 179.3 to 690.1 microg
      kg( - 1) and Hg(0) accounted for the majority at all sample sites, ranging from
      42% to 56% of the total.

PMID- 18821026
TI  - Ontogenetic development of digestive enzymes and effect of starvation in miiuy
      croaker Miichthys miiuy larvae.
AB  - The ontogenetic development of the digestive enzymes amylase, lipase, trypsin,
      and alkaline phosphatase and the effect of starvation in miiuy croaker Miichthys
      miiuy larvae were studied. The activities of these enzymes were detected prior to
      exogenous feeding, but their developmental patterns differed remarkably. Trypsin
      activity continuously increased from 2 days after hatching (dah), peaked on 20
      dah, and decreased to 25 dah at weaning. Alkaline phosphatase activity oscillated
      at low levels within a small range after the first feeding on 3 dah. In contrast,
      amylase and lipase activities followed the general developmental pattern that has
      been characterized in fish larvae, with a succession of increases or decreases.
      Amylase, lipase, and trypsin activities generally started to increase or decrease
      at transitions from endogenous to exogenous feeding or diet changes, suggesting
      that these enzymatic activities can be modulated by feeding modes. The activities
      of all the enzymes remained stable from 25 dah onwards, coinciding with the
      formation of gastric glands and pyloric caecum. These results imply that specific
      activities of these enzymes underwent changes due to morphological and
      physiological modifications or diet shift during larval development but that they
      became stable after the development of the digestive organs and associated glands
      was fully completed and the organs/glands functioned. Trypsin and alkaline
      phosphatase were more sensitive to starvation than amylase and lipase because
      delayed feeding up to 2 days after mouth opening was able to adversely affect
      their activities. Enzyme activities did not significantly differ among feeding
      groups during endogenous feeding; however, all activities were remarkably reduced
      when delayed feeding was within 3 days after mouth opening. Initiation of larvae
      feeding should occur within 2 days after mouth opening so that good growth and
      survival can be obtained in the culture.

PMID- 18821027
TI  - Production of Prnp-/- goats by gene targeting in adult fibroblasts.
AB  - Homozygous mice devoid of functional Prnp are resistant to scrapie and prion
      propagation, but heterozygous mice for Prnp disruption still suffer from prion
      disease and prion deposition. We have previously generated heterozygous cloned
      goats with one allele of Prnp functional disruption. To obtain goats with both
      alleles of Prnp be disrupted which would be resistant to scrapie completely, a
      second-round gene targeting was applied to disrupt the wild type allele of Prnp
      in the heterozygous goats. By second-round gene targeting, we successfully
      disrupted the wild type allele of Prnp in primary Prnp (+/-) goat skin
      fibroblasts and obtained a Prnp (-/-) cell line without Prnp expression. This is
      the first report on successful targeting modification in primary adult somatic
      cells of animals. These cells were used as nuclear donors for somatic cell
      cloning to produce Prnp (-/-) goats. A total of 57 morulae or blastocytes
      developed from the reconstructed embryos were transferred to 31 recipients, which
      produced 7 pregnancies at day 35. At 73 days of gestation, we obtained one cloned
      fetus with Prnp (-/-) genotype. Our research not only indicated that multiple
      genetic modifications could be accomplished by multi-round gene targeting in
      primary somatic cells, but also provided strong evidence that gene targeting in
      adult cells other than fetal cells could be applied to introduce precise genetic
      modifications in animals without destroying the embryos.

PMID- 18821029
TI  - Cloning and expression of Bacillus thuringiensis cry11 crystal protein gene in
      Escherichia coli.
AB  - The six most toxic Pakistani isolates of Bacillus thuringiensis (SBS Bt-23, 29,
      34, 37, 45 and 47), which were previously characterized for their toxicity
      against larvae of mosquito, Anopheles stephensi, and the presence of cry4 gene,
      were used for cry11 (cry4D) gene amplification. A 1.9-kb DNA fragment of cry11
      gene was PCR-amplified, cloned in expression vector pT7-7, and then used for
      transformation of E. coli BL21C. The optimum expression was obtained with 1 mM
      IPTG at 37 degrees C for 3 h. This gene showed different percentage homologies at
      protein level with scattered mutations in the toxic region. Biotoxicity assay of
      recombinant protein showed that Cry11 of SBS Bt 45 (DAB Bt 5) was the most toxic
      protein against third instar larvae of mosquito, A. stephensi, and has
      potentiality of a bioinsecticide against mosquitoes.

PMID- 18821028
TI  - Photosystem II reaction centre quenching: mechanisms and physiological role.
AB  - Dissipation of excess absorbed light energy in eukaryotic photoautotrophs through
      zeaxanthin- and DeltapH-dependent photosystem II antenna quenching is considered
      the major mechanism for non-photochemical quenching and photoprotection. However,
      there is mounting evidence of a zeaxanthin-independent pathway for dissipation of
      excess light energy based within the PSII reaction centre that may also play a
      significant role in photoprotection. We summarize recent reports which indicate
      that this enigma can be explained, in part, by the fact that PSII reaction
      centres can be reversibly interconverted from photochemical energy transducers
      that convert light into ATP and NADPH to efficient, non-photochemical energy
      quenchers that protect the photosynthetic apparatus from photodamage. In our
      opinion, reaction centre quenching complements photoprotection through antenna
      quenching, and dynamic regulation of photosystem II reaction centre represents a
      general response to any environmental condition that predisposes the accumulation
      of reduced Q(A) in the photosystem II reaction centres of prokaryotic and
      eukaryotic photoautotrophs. Since the evolution of reaction centres preceded the
      evolution of light harvesting systems, reaction centre quenching may represent
      the oldest photoprotective mechanism.

PMID- 18821030
TI  - Reliability in the ratings of quality of life between parents and their children
      of school age with cerebral palsy.
AB  - BACKGROUND: Quality of life is recognized as an important outcome of health
      services. Ideally, the child's perspectives should be sought directly to define
      their quality of life; however, this may be limited by age and cognitive and
      language abilities. PURPOSE: In a sample of school-aged children with cerebral
      palsy (CP), we compared a parent's perspective of their child's quality of life
      with their child's own perspective, when feasible. METHODS: Forty-eight children
      completed the Pediatric Quality of Life Inventory (PedsQL) measure independently
      (n = 33/48, 69% Gross Motor Function Classification System (GMFCS) I; n = 6/48,
      12% III-V). A parent completed the proxy version and the scores were compared.
      RESULTS: Intraclass correlation (ICC) coefficients were high for physical (ICC =
      0.72, confidence interval [CI]: 0.55-0.83) and moderate for psychosocial (ICC =
      0.54, CI: 0.30-0.71) well-being, with the weakest agreement on school functioning
      and the strongest agreement for ratings of physical health. Parental ratings were
      more often lower, especially for social functioning, although children rated
      themselves lower on emotional functioning. Factors associated with a closer
      agreement between parent-child pairs included older age, male gender, higher
      social competency, functional abilities, and fewer emotional symptoms (r (2) =
      0.07-0.30). CONCLUSION: In children with CP, parents' ratings of their children's
      quality of life are generally comparable as a group to their child's self-report.
      Disparities do exist, particularly in psychosocial domains, and, therefore, the
      child's own perspective should be considered whenever feasible.

PMID- 18821031
TI  - Evaluating the effectiveness of using PROs in clinical practice: a role for
      cluster-randomised trials.
AB  - Many of us believe there are major benefits to be gained by using patient
      reported outcomes (PROs) in routine clinical practice. However, demonstrating
      tangible benefits has frequently proved elusive. Although randomised clinical
      trials (RCTs) have become accepted as the standard for comparing alternative
      forms of clinical interventions, when evaluating the effectiveness of PROs there
      are a number of challenges both in terms of study design and the subsequent
      analysis. Despite this, to date, of those investigators who have used RCTs,
      relatively few have used anything other than simple two-group randomisation and
      comparisons. Most of these trials have also failed to demonstrate convincing
      benefits to patient outcomes. We suggest that the use of PROs may result in
      modest yet important improvements to patient outcomes, and that these benefits
      may be obscured in conventional individual patient trials because of
      contamination effects. The advantages of alternative designs such as cross-over
      studies and in particular cluster-randomised trials are illustrated.

PMID- 18821032
TI  - Cold preservation of rat osteochondral tissues in two types of solid organ
      preservation solution, culture medium and saline.
AB  - We compared Dulbecco's modified Eagle's medium (DMEM), saline, Euro-Collins (EC)
      solution and University of Wisconsin (UW) solution to determine which was best
      for cold preservation of rat osteochondral tissues (OCTs). After 7 days' cold
      preservation, OCTs kept in UW solution had the highest relative viable cell
      number by the tetrazolium assay and the lowest activity of lactate dehydrogenase
      released from damaged cells. Histological evaluation revealed chondrocyte
      deformity, such as shrunken cytoplasm and pyknotic nuclei, particularly in the
      deeper layer of articular cartilage after preservation in saline and EC solution
      and predominantly in all layers if preserved in DMEM. In contrast, chondrocyte
      morphology in all layers of the articular cartilage preserved in UW solution was
      relatively unchanged and remained similar to fresh OCTs. It is therefore
      concluded that UW solution is the most suitable for cold preservation of rat OCTs
      as well as solid organs.

PMID- 18821033
TI  - SULT1E1 and ID2 genes as candidates for inherited predisposition to breast and
      ovarian cancer in Jewish women.
AB  - Mutations in currently known genes account for only a subset of breast/ovarian
      cancer risk families. Three loci (2p, 4q, 22q) seemingly harbor breast cancer
      susceptibility genes. To explore their putative role in Jewish women, 46 affected
      women representing 22 high risk families were genotyped with D2S2211, D4S392,
      D22S278 and D22S283 and two flanking markers for each locus, and mutational
      analysis of ID2 (Chromosome 2) and SULT1E1 (Chromosome 4) genes was carried out
      in seemingly linked families. No ID2 gene mutations were detected in 8 women from
      the 4 families seemingly linked to D2S2211, whereas a missense mutation
      (His224Gln) in one affected woman from a single family was detected among 9 women
      from the 4 families linked to D4S392. This mutation was not found among 153 high
      risk, 98 sporadic breast/ovarian cancer patients, or 97 healthy controls. The
      SULT1E1 gene may need to be further explored as candidate breast cancer gene.

PMID- 18821034
TI  - Patient preferences and National Health Service costs: a cost-consequences
      analysis of cancer genetic services.
AB  - The study has three aims; firstly to establish if, having been informed of their
      risk status and that gene testing is inappropriate for them, low and moderate
      risk patients have misunderstood or failed to grasp this and want a test that is
      inappropriate for them. Secondly, to elicit patients' willingness to pay for
      cancer genetic services. Thirdly, to ascertain the aspects of cancer genetics
      services that are important to high risk patients and present service
      configurations prioritised in terms of preferences accompanied by their costs
      (cost-consequences analysis). Patient preferences were gathered from 120 patients
      returning a self-administered discrete choice questionnaire issued post genetic
      risk assessment. Patients at low and moderate risk of developing breast cancer
      desired inappropriate testing. Patients at high, moderate and low risk of
      developing genetic cancer were willing to pay up to 3,000 pounds for genetic
      serviced, which exceeds the current estimated cost of providing testing and
      counselling. Counselling by a genetics associate accompanied by favourable levels
      of other attributes provided high utility and substantial cost savings.

PMID- 18821035
TI  - Medical complications drive length of stay after brain hemorrhage: a cohort
      study.
AB  - INTRODUCTION: Longer length of stay (LOS) is associated with higher complications
      and costs in ICU patients, while hospital protocols may decrease complications
      and LOS. We hypothesized that medical complications would increase LOS after
      spontaneous subarachnoid (SAH) and intracerebral (ICH) hemorrhage after
      accounting for severity of neurologic injury in a cohort of consecutively
      admitted patients. METHODS: We prospectively recorded admission characteristics,
      hospital complications, and LOS for 122 patients with SAH and 56 patients with
      ICH from February 2006 through March 2008. A multidisciplinary Neuro-ICU team
      included a dedicated pharmacist and intensivist on daily rounds. Hospital
      protocols set glucose control with intravenous insulin, ventilator bundles,
      pharmacist involvement, and hand hygiene. Associations were explored with
      univariate statistics (t-tests, ANOVA, or non-parametric statistics as
      appropriate) and linear regression (repeated after log transformation of ICU and
      hospital LOS). RESULTS: Factors associated with longer LOS after SAH and ICH were
      similar. In both SAH and ICH the strongest drivers of LOS were infection, fever,
      and acute lung injury. For SAH, vasospasm and Glasgow Coma Scale were also
      significant in some models, while in patients with ICH the volume of the initial
      bleed was significant in some models. CONCLUSION: LOS after spontaneous brain
      hemorrhage is driven by medical complications even after the adoption of
      dedicated intensive care medical staff, pharmacist involvement, and evidence
      based protocols for ICU care. Further alterations in care will be necessary to
      eliminate "preventable" complications and minimize LOS after brain hemorrhage.

PMID- 18821036
TI  - Overview of lung transplantation.
AB  - Although significant gains have been made in improving lung function and survival
      in cystic fibrosis (CF), ultimately respiratory failure is the leading cause of
      mortality in these patients. For CF patients with end stage lung disease, lung
      transplantation is an option for treatment. The field of lung transplantation has
      progressed markedly in the last 20 years. Nonetheless it remains a technically
      complex and challenging procedure, and patients are at risk for numerous short
      term and long term complications. Potential transplant recipients must be
      physically and psychologically prepared for the arduous process involved in lung
      transplantation. This article will review the history of lung transplantation,
      indications for transplantation, surgical techniques, and complications of
      transplantation.

PMID- 18821037
TI  - Significance of p53 and CD31 in astrogliomas.
AB  - BACKGROUND: Astrogliomas are the most common primary brain tumor. Its progression
      is the result of activation of oncogenes, inactivation of tumor suppressor genes
      (TSGs), and expression of various growth factors. The angiogenesis and p53 in
      astrogliomas play an important role in its grading, treatment strategies, and
      hence its clinical outcome. OBJECTIVES: To analyze the frequency of presentation
      and the possible co-expression of p53 and angiogenesis marker (CD31) and their
      clinical implications in astrogliomas. MATERIAL AND METHODS: This retrograde
      study included 45 cases with astrocytomas in the form of paraffin blocks.
      Sections were stained with hematoxylin and eosin to determine the type and
      histological grade according to WHO (2007) classification of CNS tumors.
      Immunostaining was done using anti p53 and CD31 and the results were measured as
      labeling index (LI) using image analyzer system CAS-200. RESULTS: Both p53 and
      CD31 expressions were correlated well with the histopathological grades of
      different subtypes of astrogliomas with good discrimination between low and high
      grades. Overall, a highly significant statistical correlation was observed
      between the grades of astrocytomas and the p53 and CD31 labeling indices. The
      expressions of p53 and CD31 were markedly increased in glioblastoma multiforme
      (GBM) with mean values (59.7 +/- 13.5) (P = 0.0001) and (40.7 +/- 8.9) (P =
      0.001), respectively. Obviously, these observations demonstrate that the co
      expression and increased levels of p53 and CD31 in astrogliomas are increasing as
      the tumor grade is increasing. CONCLUSION: The estimation of p53 and CD31 could
      be used as good tools to assess the grade, prognosis, and aggressiveness of the
      astroglial tumors. Thus, the two markers can be used as adjunct to the diagnosis
      and stratification of the high grade from the low-grade intrinsic brain
      astrogliomas.

PMID- 18821038
TI  - Oxidative effects of gemfibrozil on anion influx and metabolism in normal and
      Beta-thalassemic erythrocytes: physiological implications.
AB  - To further clarify some peculiar molecular mechanisms related to the physiology
      and pathophysiology of erythrocytes with respect to oxygen binding and release,
      metabolism and senescence, we investigated the oxidative effects of gemfibrozil
      in normal and beta-thalassemic red blood cells. Our results showed that the
      oxidative stress promoted by the drug, through a direct interaction with
      hemoglobin, may lead to activation of caspase 3, which in turn influences the
      band 3 anion flux and glucose metabolism. In a comparative context, we also
      evaluated the effect on band 3 and caspase 3 activation of orthovanadate (a
      phosphatase inhibitor) and t-butylhydroperoxide (a known oxidant). The results
      support the hypothesis that gemfibrozil influences band 3 function through
      several mechanisms of action, centered on oxidative stress, which induces
      significant alterations of glucose metabolism.

PMID- 18821041
TI  - A comprehensive model of health-related quality of life in Parkinson's disease.
AB  - BACKGROUND: Insight in how impairments and disabilities related to Parkinson's
      disease (PD) influence health-related quality of life (HRQoL) is required to
      review adequacy of current management strategies. METHODS: The Scales for
      Outcomes in Parkinson's disease (SCOPA) evaluation was used to assess impairments
      and disabilities. HRQoL was assessed with the EuroQol-5D Visual Analogue Scale.
      378 patients with PD who participated in the SCOPA/PROPARK cohort were assessed
      while on their usual treatment. Multiple linear regression analysis and
      structural equation modelling were used to construct a model of factors that
      influence HRQoL. RESULTS: A model with good fit was constructed that identified
      various impairments and disabilities as important contributors to HRQoL in PD. Of
      the disabilities, psychosocial well-being had a larger impact on HRQoL than
      physical functioning. Of the impairments, depression had the largest contribution
      to HRQoL, followed by axial motor symptoms, gastrointestinal symptoms, and
      urinary symptoms. In addition, pain, psychiatric and motor complications, and
      daytime sleepiness had small but significant influences on HRQoL. CONCLUSION:
      Multiple factors, including disabilities, nonmotor symptoms and axial motor
      symptoms, affect HRQoL in patients with PD. In patients who are on symptomatic
      treatment aiming to alleviate mainly motor symptoms, there is a large impact on
      HRQoL of nonmotor and nondopaminergic symptoms. Research is warranted to develop
      and evaluate management strategies for the aspects that currently impact on HRQoL
      as psychosocial well-being, depressive symptoms, axial motor symptoms,
      gastrointestinal symptoms, and urinary symptoms. These findings call for a
      multidisciplinary approach in the care of these features.

PMID- 18821042
TI  - Electrophysiological features of late-onset transthyretin Met30 familial amyloid
      polyneuropathy unrelated to endemic foci.
AB  - BACKGROUND: Through the development of gene diagnostic techniques, late-onset
      transthyretin Met30-associated familial amyloid polyneuropathy (FAP TTR Met30)
      has been shown to be more prevalent than is generally believed. OBJECTIVE: To
      examine the electrophysiological features of late-onset FAP TTR Met30 unrelated
      to endemic foci. METHODS: Nerve conduction findings in 44 cases with an onset of
      more than 50 years of age in a non-endemic area were assessed and compared with
      findings from 21 earlier-onset cases related to endemic foci. RESULTS: The extent
      of the reduction of the compound muscle action potential and, especially, the
      sensory nerve action potential was more profound in the late-onset group even
      when the decline of these indices with aging in normal control subjects was taken
      into account. The feature of predominant lower-limb involvement seemed to be more
      conspicuous in the late-onset group. Electrophysiological indices tended to be
      aggravated as the duration of neuropathic symptoms increased in the early-onset
      group, while most of these indices in the lateonset group did not show this
      correlation. A slowing of conduction velocity and a prolongation of distal
      latency, which suggests demyelination, were conspicuous in some patients.
      Pathologically, a predominant loss of small-fibers was not conspicuous in sural
      nerve biopsy specimens from late-onset patients. Large myelinated fiber density
      showed a negative correlation with the disease duration in early-onset cases, but
      not in late-onset cases. CONCLUSIONS: Electrophysiological differences between
      late- and early-onset cases were present, probably reflecting the different
      underlying pathogenic mechanisms of neuropathy. The demyelinating feature does
      not exclude the possibility of this disease.

PMID- 18821043
TI  - Hippocampal head atrophy predominance in Parkinson's disease with hallucinations
      and with dementia.
AB  - We studied regional gray matter density in the hippocampus in Parkinson's disease
      (PD) patients. We obtained magnetic resonance scans in 44 PD patients (PD
      patients with dementia (PDD) = 9, non-demented PD patients with visual
      hallucinations (PD + VH) = 16, and PD patients without dementia and without
      visual hallucinations (PD - VH) = 19) and 56 controls matched for age and years
      of education. A region of interest (ROI) of the hippocampus following voxel-based
      morphometry (VBM) procedures was used to perform group comparisons, single-case
      individual analysis and correlations with learning scores. Group comparisons
      showed that PDD patients and PD+VH patients had significant hippocampal gray
      matter loss compared to controls. In PDD patients, hippocampal gray matter loss
      involved the entire hippocampus and in PD+VH this reduction was mainly confined
      to the hippocampal head. 78 % of PDD patients, 31 % of PD+VH patients and 26 % of
      PD-VH patients had hippocampal head gray matter loss when compared to controls.
      These results suggest that in PD the neurodegenerative process in the hippocampus
      starts in the head of this structure and later spreads to the tail and that, in
      addition, memory impairment assessed by Rey's Auditory Verbal Learning Test
      (RAVLT) correlates with hippocampal head gray matter loss.

PMID- 18821044
TI  - High rate of restenosis after carotid artery stenting in patients with high-grade
      internal carotid artery stenosis. Medium-term follow-up.
AB  - OBJECTIVE: Carotid endarterectomy (CEA) is the gold-standard procedure for the
      majority of patients with high-grade symptomatic internal carotid artery stenosis
      and also for specified high-grade asymptomatic stenoses; however, a proportion of
      patients are treated with carotid endovascular therapy. We aimed to document
      medium-term clinical and neurosonographical outcome after carotid artery stenting
      (CAS). METHODS: 53 patients (mean age: 65 +/- 8 years) with high-grade (> or = 70
      % by means of duplex sonography) carotid artery stenosis were enrolled into the
      study. Nineteen patients had asymptomatic, 34 patients had symptomatic stenoses.
      All patients had a pre-interventional CT, Doppler and duplex sonography, and
      digital subtraction angiography (DSA) or magnetic resonance angiography (MRA)
      prior to the procedural DSA. All patients were offered CEA as the gold-standard
      procedure and as an alternative to CAS. Both clinical and Duplex sonographical
      follow-up was obtained at day 1 and 7, month 1, month 3, month 6, month 12, and
      every subsequent 6 months after the procedure. Mean follow-up time was 22 +/- 1.6
      months (+/- SEM). RESULTS: 2/53 patients suffered from stroke. A further 2
      patients suffered from carotid artery occlusion shortly after CAS. The cumulative
      rate of restenosis during follow-up was 24.5 % (13/53). Four of these (7.5 %)
      were of high-grade and led to further interventional or surgical therapy.
      CONCLUSIONS: A high rate of restenosis was found during follow-up after CAS. Our
      analysis of non-selected patients emphasizes that CEA remains the gold-standard
      procedure for the treatment of symptomatic internal carotid artery stenosis. The
      frequently performed endovascular treatment of carotid stenosis outside the
      setting of a randomized controlled trial is not supported by our data.

PMID- 18821045
TI  - Hemispheric asymmetry of the arcuate fasciculus: a preliminary diffusion tensor
      tractography study in patients with unilateral language dominance defined by Wada
      test.
AB  - OBJECTIVE: Lateralization of language function is a prominent feature of human
      brain function, and its underlying structural asymmetry has been recently
      reported in normal right-handed subjects. By means of diffusion tensor
      tractography (DTT), we investigated the asymmetry of the language network,
      namely, the arcuate fasciculus in patients in whom the unilateral language
      dominance was defined by Wada test. METHODS: DTT was performed in 24 patients
      with a focal lesion or an epileptic focus outside the C-shaped segment of the
      arcuate fasciculus. The arcuate fasciculus was reconstructed by placing two
      regions-of-interest in the deep white matter lateral to the corona radiata. The
      pathway was then divided into one terminating in the temporal lobe (FT tract) and
      the other in the parietal lobe (FP tract). The relative number and volume of the
      FT and FP tracts in each hemisphere were submitted to repeated measure ANOVA
      separately, with the hemisphere as a within-subject factor and with the side of
      pathology as a between subject factor. RESULTS: The FT tract showed a
      significantly larger number and volume in the language dominant hemisphere than
      in the non-dominant hemisphere, while, for the FP tract, no significant
      hemispheric difference was observed in the relative number or volume. There was a
      tendency that the FT tract was less lateralized when the pathology was located in
      the dominant hemisphere than in the non-dominant hemisphere. CONCLUSION:
      Dominance of the FT tract in the language dominant hemisphere was demonstrated
      for the first time in a patient population and implicated a clinical utility of
      DTT for non-invasive evaluation of language lateralization. Our preliminary study
      might indicate reorganization of the language network in conjunction with
      pathology.

PMID- 18821046
TI  - The Frontal Assessment Battery (FAB) in Parkinson's disease and correlations with
      formal measures of executive functioning.
AB  - BACKGROUND: The Frontal Assessment Battery (FAB) is a short tool for the
      assessment of executive functions consisting of six subtests that explore
      different abilities related to the frontal lobes. Several studies have indicated
      that executive dysfunction is the main neuropsychological feature in Parkinson's
      disease (PD). GOALS: To evaluate the clinical usefulness of the FAB in
      identifying executive dysfunction in PD; to determine if FAB scores in PD are
      correlated with formal measures of executive functions; and to provide normative
      data for the Portuguese version of the FAB. METHODS: The study involved 122
      healthy participants and 50 idiopathic PD patients. We compared FAB scores in
      normal controls and in PD patients matched for age, education and Mini-Mental
      State Examination (MMSE) score. In PD patients, FAB results were compared to the
      performance on tests of executive functioning. RESULTS: In the healthy subjects,
      FAB scores varied as a function of age, education and MMSE. In PD, FAB scores
      were significantly decreased compared to normal controls, and correlated with
      measures of executive functions such as phonemic and semantic verbal fluency
      tests, Wisconsin Card Sorting Test and Trail Making Test Part A and Part B.
      CONCLUSION: The FAB is a useful tool for the screening of executive dysfunction
      in PD, showing good discriminant and concurrent validities. Normative data
      provided for the Portuguese version of this test improve the accuracy and
      confidence in the clinical use of the FAB.

PMID- 18821047
TI  - Intact serotonergic and dopaminergic systems in two cases of orthostatic tremor.

PMID- 18821048
TI  - Reversible progressive cognitive decline due to herpes simplex type 2
      encephalitis with normal MR imaging.

PMID- 18821050
TI  - Cognitive impairment in myotonic dystrophy type 1 (DM1): a longitudinal follow-up
      study.
AB  - OBJECTIVE: To characterize the progression of the cognitive involvement in
      patients affected by myotonic dystrophy type 1 (DM1) by a longitudinal
      neuropsychological follow-up study. METHODS: In a previous study we documented an
      ageing-related decline of frontal and temporal cognitive functions in
      juvenile/adult forms of DM1, irrespectively of the n(CTG) in leukocytes and the
      severity of muscle weakness. Here we present the results of a neuropsychological
      follow-up study performed in 34 out of 70 DM1 patients previously studied.
      Patients were divided into four groups according to their genotype (E1:50-150;
      E2:150-500; E3:500-1000; E4: >1000 CTG). The neuropsychological test battery
      included MMSE, memory, linguistic, level, praxis, attentional and frontal
      executive tasks. Statistical analysis was performed by One way MANOVA with
      repeated measures analysis and by Wilcoxon match paired test. RESULTS: The whole
      group of patients showed a significant deterioration in linguistic functions,
      together with a tendency towards decline in executive abilities, confirming a
      predominant involvement of cognitive functions subserved by fronto-temporal
      areas. We found no significant correlation between the progression of cognitive
      decline and the n(CTG) in leukocytes. Moreover, we observed that patients
      belonging to E2 group, with the highest mean age, got scores lower than E3
      patients, with particular regard both to linguistic and executive tasks.
      CONCLUSIONS: These data support our previous hypothesis that the cognitive damage
      is confined to frontotemporal functions in adult DM1 patients, with a tendency
      towards a decline with aging.

PMID- 18821049
TI  - Dirty-appearing white matter in multiple sclerosis: preliminary observations of
      myelin phospholipid and axonal loss.
AB  - "Dirty-appearing white matter" (DAWM) in multiple sclerosis (MS) is defined as a
      region(s) with ill-defined borders of intermediate signal intensity between that
      of normal-appearing white matter (NAWM) and that of plaque on T(2)-weighted and
      proton density imaging. To delineate the histopathology of DAWM, four formalin
      fixed cerebral hemisphere slices of three MS patients with DAWM were scanned with
      T(2)- weighted and proton density sequences. The myelin water fraction (MWF) was
      obtained by expressing the short T(2) component as a fraction of the total T(2)
      distribution. Hemispheric sections were then stained with Luxol fast blue (LFB)
      for myelin phospholipids, for myelin basic protein (MBP) and 2',3'-cyclic
      nucleotide 3'-phosphohydrolase (CNP) for myelin; Bielschowsky silver impregnation
      for axons; and for glial fibrillary acidic protein (GFAP) for astrocytes.
      Compared to NAWM, DAWM showed reduction in MWF, corresponding to a reduction of
      LFB staining. DAWM also showed reduced Bielschowsky staining. Quantitatively, the
      change in MWF in DAWM most consistently correlated with the change in LFB
      staining. The findings of this preliminary study suggest that DAWM is
      characterized by loss of myelin phospholipids, detected by the short T(2)
      component, and axonal reduction.

PMID- 18821052
TI  - Dietary L-arginine supplementation alleviates immunosuppression induced by
      cyclophosphamide in weaned pigs.
AB  - A study was conducted to investigate the effects of L-arginine (Arg) on
      performance and immune function in cyclophosphamide (CY) immunosuppressed weaned
      pigs. The weaned pigs were allotted randomly into one of three treatments,
      including: (1) non-challenged control; (2) CY-challenged group; and (3) CY + 0.5%
      Arg. On days 14 and 21 of the trial, pigs were injected with CY or sterile
      saline. Blood samples were obtained on days 21 and 28 of the trial for further
      analysis. On day 28, delayed-type hypersensitivity reaction was evaluated. Arg
      alleviated the decrease of average daily gain (P < 0.05) induced by CY challenge
      from days 21 to 28. Arg mitigated the CY-induced decrease of total white blood
      cell numbers (P < 0.05) on day 28 and improved the lymphocyte percentage on day
      21 (P < 0.05). Arg increased the delayed-type hypersensitivity reaction (P <
      0.05), and attenuated the decrease of bovine serum albumin antibody level caused
      by CY treatment (P < 0.05) on day 28. In addition, Arg elevated the levels of
      serum interleukin-2 and interferon-gamma (P < 0.05) on day 28, and mitigated the
      decrease of serum interferon-gamma level on day 21 (P < 0.05). These results
      indicate that Arg supplementation has beneficial effects in attenuating the
      immunosuppressive effects of CY challenge, therefore improving growth performance
      of young pigs.

PMID- 18821053
TI  - Chronic methionine load-induced hyperhomocysteinemia impairs the relaxation
      induced by bradykinin in the isolated rat carotid.
AB  - This study investigates the effects of chronic methionine intake on bradykinin
      (BK)-relaxation. Vascular reactivity experiments were performed on carotid rings
      from male Wistar rats. Treatment with methionine (0.1, 1 or 2 g kg(-1) per day)
      for 8 and 16 weeks, but not for 2 and 4 weeks, reduced the relaxation induced by
      BK. Indomethacin, a non-selective cyclooxygenase (COX) inhibitor, and SQ29548, a
      selective thromboxane A(2) (TXA(2))/prostaglandin H(2) (PGH(2)) receptor
      antagonist prevented the reduction in BK-relaxation observed in the carotid from
      methionine-treated rats. Conversely, AH6809, a selective prostaglandin F(2alpha)
      (PGF(2alpha)) receptor antagonist did not alter BK-relaxation in the carotid from
      methionine-treated rats. The nitric oxide synthase (NOS) inhibitors L-NAME, L-NNA
      and 7-nitroindazole reduced the relaxation induced by BK in carotids from control
      and methionine-treated rats. In summary, we found that chronic methionine intake
      impairs the endothelium-dependent relaxation induced by BK and this effect is due
      to an increased production of endothelial vasoconstrictor prostanoids (possibly
      TXA(2)) that counteracts the relaxant action displayed by the peptide.

PMID- 18821054
TI  - Using multidimensional patterns of amino acid attributes for QSAR analysis of
      peptides.
AB  - On the basis of exploratory factor analysis, six multidimensional patterns of 516
      amino acid attributes, namely, factor analysis scales of generalized amino acid
      information (FASGAI) involving hydrophobicity, alpha and turn propensities, bulky
      properties, compositional characteristics, local flexibility and electronic
      properties, are proposed to represent structures of 48 bitter-tasting dipeptides
      and 58 angiotensin-converting enzyme inhibitors. Characteristic parameters
      related to bioactivities of the peptides studied are selected by genetic
      algorithm, and quantitative structure-activity relationship (QSAR) models are
      constructed by partial least square (PLS). Our results by a leave-one-out cross
      validation are compared with the previously known structure representation method
      and are shown to give slightly superior or comparative performance. Further, two
      data sets are divided into training sets and test sets to validate the
      characterization repertoire of FASGAI. Performance of the PLS models developed by
      training samples by a leave-one-out cross validation and external validation for
      test samples are satisfying. These results demonstrate that FASGAI is an
      effective representation technique of peptide structures, and that FASGAI vectors
      have many preponderant characteristics such as straightforward physicochemical
      information, high characterization competence and easy manipulation. They can be
      further applied to investigate the relationship between structures and functions
      of various peptides, even proteins.

PMID- 18821055
TI  - Does perceived safety of light cigarette encourage smokers to smoke more or to
      inhale more deeply?
AB  - OBJECTIVES: This study investigated the effect of smoking light cigarettes and
      believing that light cigarettes are less of a health threat on the decision to
      smoke more light cigarettes or inhale more deeply in Taiwan. METHODS: Demographic
      and smoking characteristic data for 1,182 smokers who believe that smoking light
      cigarettes is relatively safe was obtained from the 2002 Survey of the Health
      Promotion Knowledge, Attitudes, and Behavior of Taiwan Citizens; this data was
      used to establish Logit models for the decision to smoke more light cigarettes or
      inhale more deeply. RESULTS: Respectively 5.64% and 4.76% of the light cigarette
      smokers were motivated to smoke more light cigarettes or inhale more deeply by
      their belief that light cigarettes are relatively safe. Light cigarette smokers,
      who believe that light cigarettes are relatively safe and who wish to quit
      smoking, and light smokers, are both likely to smoke more light cigarettes or
      inhale light cigarettes more deeply in comparison to ordinary cigarette smokers.
      CONCLUSIONS: Government should attempt to reverse the tendency for light smokers
      to smoke more under the misconception that light cigarettes are relatively safe,
      and correct the erroneous belief among smokers who wish to quit that smoking
      light cigarettes is an intermediate stage on the path to quitting.

PMID- 18821056
TI  - Suicide and alcohol-related mortality in Hungary in the last two decades.
AB  - OBJECTIVES: Suicide and alcohol-related mortality are often linked to each other
      in recent times, especially in the unfavourable mortality trends detected in
      Russia. Recent study has aimed to investigate suicide and alcohol-related
      mortality in Hungary between 1986 and 2005. This paper is based on the concept of
      social anomie and expects to find more favourable trends for both causes of death
      among those who were less exposed to unfavourable economic and social trends in
      the last two decades. METHODS: In a cross-sectional design sex, age- and
      education-specific mortality rates were calculated. RESULTS: We found falling
      suicide rates in all socio-demographic groups, except well-educated middle aged
      men. Suicide has fallen more among women than men, more among the elderly than
      the young and more among the more educated than the less educated. Alcohol
      related mortality has risen by 5-10 %, and its occurrence in different socio
      demographic groups was found to be changing entirely proportionally. CONCLUSIONS:
      Developments in suicide mortality are generally in accordance with the hypothesis
      based on the concept of social anomie while those of alcohol-related mortality
      showed no relation with this concept.

PMID- 18821057
TI  - The three-fingered protein domain of the human genome.
AB  - Extracellular domains of some cellular receptors expressed in the organisms at
      different levels of development belong to three-fingered protein (TFP) fold. The
      Homo sapiens genome encodes at least 45 genes containing from one to three TFP
      domains (TFPDs), namely diverse paralogues of the Ly6 gene, CD59 and the
      receptors of activins, bone morphogenetic proteins, Mullerian inhibiting
      substance and transforming growth factor-beta. C4.4a and urokinase/plasminogen
      activatory receptor contain two and three TFPD repeats, respectively. These
      diverse proteins have a low overall sequence similarity with each other and their
      hydrophobicity levels vary to a considerable degree. It is suggested that
      sequence differentiation within the TFPD led to distinct groups of proteins whose
      attributes were optimized to fit both the physicochemical properties specific to
      their functional microenvironment and selective targeting of their highly
      diversified extracellular cofactors.

PMID- 18821058
TI  - An acceptor-substrate binding site determining glycosyl transfer emerges from
      mutant analysis of a plant vacuolar invertase and a fructosyltransferase.
AB  - Glycoside hydrolase family 32 (GH32) harbors hydrolyzing and transglycosylating
      enzymes that are highly homologous in their primary structure. Eight amino acids
      dispersed along the sequence correlated with either hydrolase or
      glycosyltransferase activity. These were mutated in onion vacuolar invertase
      (acINV) according to the residue in festuca sucrose:sucrose 1
      fructosyltransferase (saSST) and vice versa. acINV(W440Y) doubles transferase
      capacity. Reciprocally, saSST(C223N) and saSST(F362Y) double hydrolysis.
      SaSST(N425S) shows a hydrolyzing activity three to four times its transferase
      activity. Interestingly, modeling acINV and saSST according to the 3D structure
      of crystallized GH32 enzymes indicates that mutations saSST(N425S), acINV(W440Y),
      and the previously reported acINV(W161Y) reside very close together at the
      surface in the entrance of the active-site pocket. Residues in- and outside the
      sucrose-binding box determine hydrolase and transferase capabilities of GH32
      enzymes. Modeling suggests that residues dispersed along the sequence identify a
      location for acceptor-substrate binding in the 3D structure of
      fructosyltransferases.

PMID- 18821059
TI  - Molecular cloning and characterization of phosphate (Pi) responsive genes in Gulf
      ryegrass (Lolium multiflorum L.): a Pi hyperaccumulator.
AB  - Gulf annual ryegrass has been identified as potential Pi hyperaccumulator,
      however the molecular mechanism remains largely unknown. A suppression
      subtractive hybridization (SSH) analysis was used to evaluate the phosphate (Pi)
      responsive genome expression pattern changes in Gulf annual ryegrass (Lolium
      multiflorum L.). Differential screening identified 384 putative Pi-starvation
      induced cDNAs. Bioinformatic analysis revealed that 116 cDNAs are nonredundant
      unigenes of which 108 exhibited high similarities with Genbank entries. The
      differential expression patterns of 13 cDNAs, representing diverse functional
      categories, were confirmed by RNA gel blot analysis. Further, detailed molecular
      analysis of three genes (LmPAP1, LmIPS1 and LmIDS1) was carried out by cloning
      and characterization of full-length cDNAs. LmPAP1 is 1,414 bp in length with an
      open reading frame (ORF) of 1,188 bp capable of encoding an N-terminal signal
      peptide of 26 amino acids. LmIPS1 gene is a member of TPSI1/Mt4 family that
      contains 3 short ORFs. The cDNA of LmIDS1 is 346 bp in size including a single
      ORF of 222 nucleotides that encodes 74 amino acid proteins, exhibiting homology
      with IDS1 with similarity to type 2 metallothionein like protein. In our
      preliminary screening of different genotypes of annual ryegrass for
      hyperaccumulation of Pi in their shoots, Gulf and Urugrary showed significant
      differences with values of 1.0% and 0.7%, respectively. Since it is logical to
      assume a plausible correlation that may exist between Pi-accumulation in the
      shoots and the expression of Pi-responsive genes, the expression of LmPAP1,
      LmIPS1 and LmIDS1 was evaluated in these two genotypes grown under different Pi
      regimes. Although there was a significant induction of these genes in both the
      genotypes grown under Pi-deprived condition, the abundance of LmPAP1 transcripts
      was relatively higher in the Gulf genotype as compared to that in the Urugrary
      genotype. A similar trend was observed in qRT-PCR data of other tested genotypes
      of annual ryegrasses. This suggests the potential role of LmPAP1 in accumulation
      of Pi in Gulf grass. In addition, Gulf grass genotype revealed higher levels of
      total P, (33)Pi uptake, and APase activity as compared to Urugrary. Together,
      these results suggest that the Gulf ryegrass has evolved mechanisms to acquire
      and hyperaccumulate more Pi under different Pi regimes by activating multiple Pi
      acquisition and mobilization mechanisms.

PMID- 18821060
TI  - Inhibition of prostate cancer metastasis by administration of a tissue vaccine.
AB  - Immunotherapy by vaccination represents a novel method for treatment of cancer.
      In this regard, vaccines with the broadest possible menu of relevant antigens
      stand the greatest chance of success. Tissue vaccines are composed of material
      harvested directly from tumors and contain not only antigens associated with
      neoplastic epithelium, but also those that may be unique to in vivo growth and
      antigens associated with the tumor stroma. To test the hypothesis that a tissue
      vaccine, produced by glutaraldehyde fixation of harvested syngeneic prostate
      tumors (GFT vaccine), could be used for treatment of prostate cancer, male Lobund
      Wistar (LW) rats were treated with methylnitrosourea (MNU) and testosterone
      propionate to induce autochthonous prostate tumors. Tumor-bearing rats were
      randomly assigned to one of three treatment groups: no treatment (11 rats);
      vaccination with media (10 rats); or vaccination with the GFT vaccine (19 rats).
      Vaccination was given initially with Freund's complete adjuvant and booster doses
      were given with incomplete Freund's adjuvant every week until the time of
      euthanasia. There were no significant differences in mean tumor weight between
      groups; however, GFT-vaccinated rats had a prolonged survival time; and 4/19
      (21%) GFT-vaccinated rats were found to be tumor-free compared to none of the
      untreated or media-treated controls. Further, pulmonary metastasis occurred in
      only 5/15 (33%) of GFT-vaccinated rats compared to 10/11 (91%) and 10/10 (100%)
      of untreated and media-vaccinated controls, respectively. Supernatants of
      cultured splenocytes from similarly media- and GFT-vaccinated rats demonstrated
      significant (P < 0.001) increases in IFN-gamma and TNF-alpha from splenocytes of
      GFT-vaccinated rats, suggesting that GFT vaccination stimulates a Th1 response.
      In summary, treatment of tumor-bearing rats with a tissue vaccine stimulated a
      protective immune response that resulted in complete tumor regression in 21% of
      animals and reduced the number of animals with any evidence of metastasis by
      nearly 70%. These results suggest that tissue vaccines may be useful for the
      treatment of prostate cancer.

PMID- 18821061
TI  - Daidzein-metabolizing phenotypes in relation to mammographic breast density among
      premenopausal women in the United States.
AB  - BACKGROUND: Mammographic breast density is an established marker of breast cancer
      risk, and is hormonally sensitive. Studies suggest that production of the
      daidzein metabolites equol and O-Desmethylangolensin (ODMA) may be associated
      with hormones and hormonally mediated factors, but few studies have assessed
      relationships between the capacity to produce these metabolites and breast
      density. OBJECTIVE: To evaluate the relationship between equol- and ODMA-producer
      phenotypes and breast density in premenopausal women in the United States.
      DESIGN: Two hundred and three women attended a clinic visit and 200 provided a
      urine sample following a 3 day soy challenge. Samples were analyzed for
      isoflavones by GC-MS to determine daidzein-metabolizing phenotypes. Percent
      density on recent (<14 month prior to their clinic visit) mammograms was assessed
      by one reader using a computer-assisted method. Multiple regression analysis was
      used to assess relationships between the production of equol and ODMA and breast
      density. Results 55(27.5%) and 182(91%) women were classed as equol- and ODMA
      producers (>87.5 ng/ml urine), respectively. In unadjusted and adjusted analyses,
      there were no differences in breast density between producers and non-producers
      of either equol or ODMA (P > 0.05). CONCLUSION: In this population of low-soy
      consuming premenopausal women, there were no associations between daidzein
      metabolizing phenotypes and breast density, suggesting that these phenotypes per
      se do not influence premenopausal breast density.

PMID- 18821062
TI  - Green tea catechins inhibit angiogenesis through suppression of STAT3 activation.
AB  - Previous studies indicate that green tea extract may inhibit breast cancer
      progression by blocking angiogenesis, although the molecular mechanisms are not
      well defined. We demonstrate that administration of Polyphenon E (Poly E), a
      standardized green tea extract, inhibited MDA-MB231 breast cancer and human
      dermal microvascular endothelial (HMVEC) cell migration and the expression of
      vascular endothelial growth factor (VEGF) and matrix metalloproteinase 9 (MMP9).
      In addition, Poly E inhibited VEGF-induced neovascularization in vivo. We also
      demonstrate that Poly E blocked signal transducers and activators of
      transcription (STAT) signaling by suppressing interferon-gamma (IFN-gamma)
      induced gene transcription via IFN-gamma-activating sequence (GAS) elements and
      downstream STAT3 activation by inhibiting STAT1 and STAT3 dimerization in MDA
      MB231 cells. Transient expression of constitutively active STAT3 significantly
      reduced the inhibitory effect of Poly E on cell migration and VEGF and MMP9
      expression. Taken together, these observations indicate that green tea extract
      inhibits angiogenesis partly through the disruption of STAT3-mediated
      transcription of genes, including VEGF.

PMID- 18821063
TI  - Newborn screening for cystic fibrosis.
AB  - Newborn screening (NBS) for cystic fibrosis (CF) has evolved considerably from
      its beginnings. We review the early history of NBS in the USA and the evolution
      of CF NBS from its conception in observational studies, to the development of
      mass-screening methodology in the 1970s, and to its early applications in the USA
      and other countries. We review the development of current CF NBS algorithms,
      particularly the development of those used in the Wisconsin randomized controlled
      trial, and discuss the comparative utility of different algorithms. We also
      discuss the identified nutritional and respiratory benefits of CF NBS, discuss
      treatment strategies for newborns identified with CF, and also discuss
      opportunities for slowing the progression of this disease.

PMID- 18821064
TI  - shRNA expression plasmids generated by a novel method efficiently induce gene
      specific knockdown in a silkworm cell line.
AB  - RNAi knockdown by using shRNA expression plasmids is widely used to determine the
      function of individual genes in mammals. Here we developed a simple method to
      create an IR DNA in a U6 small nuclear RNA promoter-based parent vector using a
      single-stranded IR DNA with short hairpin structure and Bst DNA polymerase.
      Furthermore, we demonstrated that the shRNA expression plasmids constructed by
      our method effectively induced target-specific RNAi in the silkworm cell line. We
      also found that sequence preference in the silkworm cell line was much lower than
      in mammalian cells and shRNA-induced RNAi was influenced by the length of the
      stem region.

PMID- 18821065
TI  - Nanosecond electroporation: another look.
AB  - As the medical field moves from treatment of diseases with drugs to treatment
      with genes, safe and efficient gene delivery systems are needed to make this
      transition. One such safe, non-viral, and efficient gene delivery system is
      electroporation (electrogenetherapy). Exciting discoveries using electroporation
      could make this technique applicable to drug and vaccine delivery in addition to
      gene delivery. Typically milli and microsecond pulses have been used for
      electroporation. Recently, the use of nanosecond electrical pulses (10-300 ns) at
      very high magnitudes (10-300 kV/cm) has been studied for direct DNA transfer to
      the nucleus in vitro. This article reviews the work done using high-intensity
      nanosecond pulses, termed as nanosecond electroporation (nsEP), in
      electroporation gene delivery systems.

PMID- 18821066
TI  - Axillary lymph node metastasis in lung cancer.
AB  - STUDY OBJECTIVES: Axillary lymph node metastasis (ALNM) from lung cancer is rare.
      Its prognosis and effective treatments remain unknown. To evaluate
      clinicopatholgical characteristics of such lung cancer patients, we performed a
      retrospective study of them, who had ALNM at the time of initial presentation or
      developed ALNM in their clinical courses. METHODS: We reviewed the medical
      records and pathological reports of all patients at our division who had a
      diagnosis of primary lung cancer from January 1985 through August 2007. RESULTS:
      Ten (0.75%) of 1,340 patients had ALNM. In eight of them, ALNM was detected at
      the time of initial diagnosis, and two patients developed ALNM in their clinical
      courses. Lymphatic metastasis to mediastinum was evident in all patients.
      Supraclavicular and cervical lymph nodes were involved in five and three
      patients, respectively. One patient had direct chest wall invasion from the lung.
      Three patients had distant metastases other than axillary or cervical lymph
      nodes. Four patients received systemic chemotherapy, and another four patients
      received palliative chest irradiation or supportive care because of their poor
      performance status. Median survival time of 8 patients who were diagnosed as
      having ALNMs at initial presentation was 7 months. CONCLUSIONS: The most likely
      mechanism for axillary node involvement is intercostal lymphatics via spread from
      mediastinal lymph node metastasis. Routine palpation of the axillae is
      recommended if chest wall invasion, mediastinal and/or supraclavicular lymph
      nodes are found either at initial presentation or at follow-up of patients.

PMID- 18821067
TI  - Risk-adapted management for patients with clinical stage I non-seminomatous germ
      cell tumour of the testis.
AB  - Testis cancer is the most common cancer in young men and its incidence continues
      to rise. Even if prognosis is considered as good, a group with bad prognosis
      still remains. We aimed to evaluate whether two courses of chemotherapy after
      orchiectomy in patients with clinical stage I, non-seminomatous germ cell
      testicular tumour at high risk of relapse, will spare patients additional
      chemotherapy or surgery. High-risk patients had one or more of the following:
      preorchiectomy alpha-fetoprotein level of 80 ng/dl, 80% embryonal cell carcinoma
      or greater, vessel invasion in the primary tumour and tumour stage pT2 or
      greater. Low-risk patients had none of these factors or had 50% teratoma or more
      without vessel invasion. High-risk patients were offered two 21-day courses of
      outpatient chemotherapy consisting cisplatin, etoposide and bleomycin (BEP). Low
      risk patients were observed. Of the 108 patients, we classified 71 as high risk
      and 37 as low risk of relapse. All of the high-risk patients received two courses
      of BEP chemotherapy. Low-risk patients were kept on close-up. The median follow
      up was 26 months (range 10-60). Of the 71 patients in high-risk group, 3 relapsed
      with viable cancer and required additional chemotherapy and 1 patient with normal
      biomarkers and a late-appearing mass underwent retroperitoneal lympadenectomy for
      mature teratoma. All 4 relapsed patients were in high-risk group and presently
      they are free of disease. None of the 37 patients at low risk of recurrences
      developed relapse. We recommend two courses of adjuvant chemotherapy after
      postorchiectomy for high-risk patients with stage I non-seminomatous germ cell
      tumour of the testis. Adjuvant chemotherapy for these patients results in a low
      relapse and morbidity, wich compares favourably with the results of surveillance
      or RPLND. This well-tolerated approach may spare patients additional surgery or
      protracted chemotherapy, reduce the cost and eliminate the compliance problems
      associated with intensive follow up of high-risk patients.

PMID- 18821068
TI  - Tobramycin Nebulizer Solution in severe COPD patients colonized with Pseudomonas
      aeruginosa: effects on bronchial inflammation.
AB  - INTRODUCTION: Airway colonization with Pseudomonas aeruginosa is frequent in
      severe chronic obstructive pulmonary disease (COPD) and may lead to progressive
      inflammatory damage. Inhaled Tobramycin Nebulizer Solution (TNS; a preservative
      free formulation) is an effective therapy in chronic P aeruginosa infection in
      cystic fibrosis and bronchiectasis. In this study we aimed to investigate the
      effects of a TNS short course on inflammatory markers in bronchial secretions
      from multiresistant P aeruginosa-colonized patients with severe COPD. To the
      authors' knowledge, this is the first study to examine this in cases of severe
      COPD. METHODS: Thirteen COPD patients (GOLD criteria 3-4; mean age 72.7+/- 8
      years; mean basal forced expiratory volume in 1 second (FEV(1)) 34.8%+/-8.1%;
      mean FEV(1)/forced vital capacity 0.6+/-0.1) were enrolled. All patients were
      colonized with P aeruginosa and resistant to oral/intravenous specific
      antibiotics. Eosinophilic cationic protein (ECP), interleukin-1 beta (IL-1beta),
      interleukin-8 (IL-8), tumor necrosis factor alfa (TNF-alpha), and cell counts
      were measured in spontaneous secretions before and after a 2-week TNS course (300
      mg twice daily). RESULTS: The TNS course induced a significant reduction in IL
      1beta (P<0.03), IL-8 (P<0.02), ECP (P<0.01) concentrations, and in eosinophil
      count (P<0.01). TNF-alpha levels, and neutrophil and lymphocyte counts were not
      significantly affected. The second week of treatment proved crucial in terms of
      efficacy. P aeruginosa density was lowered after 6 months; severe acute
      exacerbations were reduced by 42%. CONCLUSION: TNS reduced the inflammatory
      impact of P aeruginosa in multiresistant, P aeruginosa-colonized patients with
      severe COPD. A therapeutic role for TNS can be strongly suggested in these
      particular conditions.

PMID- 18821069
TI  - Fournier's gangrene: is it scrotal gangrene?
AB  - INTRODUCTION: Fournier's gangrene was originally described as scrotal gangrene in
      young males. Today, it is generally accepted as synergistic necrotizing fasciitis
      of perineal, genital, or perianal regions, and the epidemiologic data have
      changed. However, there are still limited data about females due to the lack of
      female patients, even in large case series. METHODS: A retrospective review of
      the medical records of all patients who received surgery for emergency conditions
      over the past 22 years was performed to identify patients with Fournier's
      gangrene. Data from these patients were then reviewed to determine the age,
      gender, etiology, causative bacteria, predisposing factors, treatment modalities,
      length of hospital stay, and morbidity and mortality rates associated with
      Fournier's gangrene. Data were evaluated using multivariate analyses. RESULTS:
      Sixty-five patients (20 female) were identified with the diagnosis of Fournier's
      gangrene. The mean age was 50.8 years. The most common etiology was
      hemorrhoidectomy in male and perianal abscess in female patients. The most
      commonly isolated microorganism in both male and female patients was Escherichia
      coli. Twenty-nine patients had diabetes mellitus, which was the most common
      predisposing factor. Mean hospitalization time was 24.4 days and the overall
      mortality was 27.70%. CONCLUSION: Fournier's gangrene is still an important
      disease with high mortality rates in spite of the developments in intensive care
      units and new-generation antibiotics. It seems that there are no major
      differences between male and female patients in the characteristics of the
      condition.

PMID- 18821070
TI  - Prognostic value of preoperative CEA, CA 19-9, CA 72-4, and AFP levels in gastric
      cancer.
AB  - INTRODUCTION: Recent research has suggested that serum tumor markers can give
      valuable prognostic information in gastric cancer. In this study, we examined the
      relationship between preoperative serum carcinoembryonic antigen (CEA),
      carbohydrate antigen (CA) 19-9, CA 72-4, and alfa fetoprotein (AFP) levels on
      clinicopathologic significance in gastric cancer patients. METHODS: Preoperative
      plasma levels of CEA, CA 19-9, CA 72-4, and AFP were retrospectively examined in
      95 patients who underwent surgical resection for gastric cancer, and the
      prognostic value of the tumour markers were estimated. RESULTS: The percentage of
      CA 19-9, CA 72-4, CEA, and AFP-positive cases were 41%, 32.6%, 24.2%, and 8.4%,
      respectively. CEA was more frequently positive in the patients with liver
      metastases (P=0.02). CA 19-9 was more frequently positive in patients with lymph
      node (P=0.005), peritoneal (P=0.01), and serosal (P=0.03) involvement. CA 72-4
      was more frequently positive in patients with lymph node (P=0.01), peritoneal
      (P=0.03), and liver (P=0.01) involvement. Low 3-year cumulative survival was
      associated significantly with elevated serum levels of CEA (P=0.001), CA 19-9
      (P=0.001), CA 72-4 (P=0.001), and AFP (P=0.01). In multivariate analysis, age,
      tumor stage, and CA 72-4 were the only independent prognostic factors. Being
      positive for CA 72-4 was associated with a 3.8-fold higher risk of death (95%
      confidence intervals: 1.3, 10.9). CONCLUSION: Our results suggest that high
      preoperative serum levels of CA 72-4 in gastric cancer patients are associated
      with a higher risk of death due to gastric cancer.

PMID- 18821071
TI  - Preparation of reference material for organochlorine pesticides in a herbal
      matrix.
AB  - The development of reference material for four organochlorine pesticides, namely
      hexachlorobenzene and three isomers of hexachlorocyclohexane (alpha
      hexachlorocyclohexane, beta-hexachlorocyclohexane and gamma
      hexachlorocyclohexane), in a ginseng root sample is presented. Raw materials
      (Panax ginseng) were purchased from a local market and confirmed to contain
      certain levels of incurred organochlorine pesticide residues by a validated gas
      chromatography-mass selective detection method. A total of more than 300 bottles
      each containing 25 g of samples were prepared after the materials had been freeze
      dried, milled and thoroughly mixed. The homogeneity and stability of samples from
      randomly selected bottles were verified and the reference values were
      characterized using a highly precise isotope dilution gas chromatography-mass
      spectrometry (ID-GCMS) method that was recently developed by our laboratory. The
      purity of standard organochlorine chemicals was determined against certified
      reference materials to establish the accuracy of the ID-GCMS analysis. The
      concentrations (+/- expanded uncertainty) of hexachlorobenzene, alpha
      hexachlorocyclohexane, beta-hexachlorocyclohexane and gamma-hexachlorocyclohexane
      in the reference material were 0.198 +/- 0.015, 0.450 +/- 0.022, 0.213 +/- 0.011
      and 0.370 +/- 0.032 mg kg(-1), respectively. A portion (70 bottles) of the
      samples was also used in a proficiency testing (PT) scheme for assessing the
      testing capabilities of field laboratories. The consensus mean values of the PT
      obtained from the 70 participants were on the same order but deviated by -2.7 to 
      14.1% from those of the assigned reference values. Because of the wide spread of
      participants' data (relative standard deviation ranging from 44 to 56%), the PT
      results were not included in the calculation of the assigned values of the
      reference materials. The materials served as suitable reference materials to
      ascertain the quality control and validation processes for the determination of
      organochlorine pesticides in herbal matrices.

PMID- 18821072
TI  - Stability of arsenic peptides in plant extracts: off-line versus on-line parallel
      elemental and molecular mass spectrometric detection for liquid chromatographic
      separation.
AB  - The instability of metal and metalloid complexes during analytical processes has
      always been an issue of an uncertainty regarding their speciation in plant
      extracts. Two different speciation protocols were compared regarding the analysis
      of arsenic phytochelatin (As(III)PC) complexes in fresh plant material. As the
      final step for separation/detection both methods used RP-HPLC simultaneously
      coupled to ICP-MS and ES-MS. However, one method was the often used off-line
      approach using two-dimensional separation, i.e. a pre-cleaning step using size
      exclusion chromatography with subsequent fraction collection and freeze-drying
      prior to the analysis using RP-HPLC-ICP-MS and/or ES-MS. This approach revealed
      that less than 2% of the total arsenic was bound to peptides such as
      phytochelatins in the root extract of an arsenate exposed Thunbergia alata,
      whereas the direct on-line method showed that 83% of arsenic was bound to
      peptides, mainly as As(III)PC(3) and (GS)As(III)PC(2). Key analytical factors
      were identified which destabilise the As(III)PCs. The low pH of the mobile phase
      (0.1% formic acid) using RP-HPLC-ICP-MS/ES-MS stabilises the arsenic peptide
      complexes in the plant extract as well as the free peptide concentration, as
      shown by the kinetic disintegration study of the model compound As(III)(GS)(3) at
      pH 2.2 and 3.8. But only short half-lives of only a few hours were determined for
      the arsenic glutathione complex. Although As(III)PC(3) showed a ten times higher
      half-life (23 h) in a plant extract, the pre-cleaning step with subsequent
      fractionation in a mobile phase of pH 5.6 contributes to the destabilisation of
      the arsenic peptides in the off-line method. Furthermore, it was found that
      during a freeze-drying process more than 90% of an As(III)PC(3) complex and
      smaller free peptides such as PC(2) and PC(3) can be lost. Although the two
      dimensional off-line method has been used successfully for other metal complexes,
      it is concluded here that the fractionation and the subsequent freeze-drying were
      responsible for the loss of arsenic phytochelatin complexes during the analysis.
      Hence, the on-line HPLC-ICP-MS/ES-MS is the preferred method for such unstable
      peptide complexes. Since freeze-drying has been found to be undesirable for
      sample storage other methods for sample handling needed to be investigated.
      Hence, the storage of the fresh plant at low temperature was tested. We can
      report for the first time a storage method which successfully conserves the
      integrity of the labile arsenic phytochelatin complexes: quantitative recovery of
      As(III)PC(3) in a formic acid extract of a Thunbergia alata exposed for 24 h to 1
      mg As(v) L(-1) was found when the fresh plant was stored for 21 days at 193 K.

PMID- 18821073
TI  - NK and NKT cell dynamics after rituximab therapy for systemic lupus erythematosus
      and rheumatoid arthritis.
AB  - Biomarkers of clinical response to rituximab (RTX) therapy and early predictors
      of outcome are still under investigation. We report a flow cytometric
      immunophenotyping analysis from peripheral blood leukocyte subpopulations of two
      patients with systemic lupus erythematosus (SLE) associated thrombocytopenia and
      one patient with rheumatoid arthritis (RA), before and after 6 weeks of treatment
      with RTX. Our results show a reduced population of CD19(+) expressing cells (B
      cells) after RTX treatment in all three patients. Increased frequency of
      peripheral regulatory CD4(+)CD25(high) T cell subset and the CD3(-)CD16(
      )CD56(bright) NK cell subset after RTX therapy were also observed in all
      patients, the latter being more pronounced in the SLE patient with sustained
      clinical response. In addition, an increased population of NKT cell subsets was
      observed in the patients with clinical response. This is the first evaluation of
      NK and NKT cells as biomarkers of clinical response after rituximab therapy in
      rheumatic diseases.

PMID- 18821074
TI  - How can calcium pyrophosphate crystals induce inflammation in hypophosphatasia or
      chronic inflammatory joint diseases?
AB  - Hypophosphatasia (HP) is a rare inborn error of bone and mineral metabolism
      characterized by a defect in the tissue non-specific alkaline phosphatase
      (TNSALP) gene. Calcium pyrophosphate dihydrate (CPPD) crystals are known to
      accumulate as substrates of TNSALP in tissues and joints of patients with HP. In
      CPPD-induced arthritis these crystals are known to induce an inflammatory
      response. HP patients do suffer from pain in their lower extremities. However, it
      is not clear whether CPPD crystals contribute to these musculoskeletal complaints
      in HP. As long as there is no curative treatment of HP, symptomatic treatment in
      order to improve clinical features, especially with regard to pain and physical
      activity, is of major interest to the patients. Knowledge of the mechanisms
      underlying crystal-induced cell activation, however, is limited. Here we describe
      recent advances in elucidating the signal transduction pathways activated by CPPD
      crystals as endogenous "danger signals". Recent investigations provided evidence
      that Toll/interleukin-1 receptor (TIR) domain containing receptors including Toll
      like receptors (TLRs) and interleukin-1 receptor (IL-1R), as well as the
      triggering receptor expressed on myeloid cells 1 (TREM-1) and the NACHT-leucin
      rich repeat and pyrin-domain-containing protein (NALP3) containing inflammasome
      are essentially involved in acute CPPD crystal-induced inflammation. These
      receptors are considered in part as components of the innate immune system.
      Further studies are needed to improve our understanding of the pathophysiological
      mechanisms leading to inflammation and tissue destruction associated with
      deposition of microcrystals. They might support the development of new
      therapeutic strategies for crystal-induced inflammation. Eventually, patients
      with HP might as well profit from such strategies addressing these metabolic
      disorders secondary to the gene defect.

PMID- 18821075
TI  - Post-transcriptional gene silencing and virus resistance in Nicotiana benthamiana
      expressing a Grapevine virus A minireplicon.
AB  - Grapevine virus A (GVA) is closely associated with the economically important
      rugose-wood disease of grapevine. In an attempt to develop GVA resistance, we
      made a GFP-tagged GVA-minireplicon and utilized it as a tool to consistently
      activate RNA silencing. Launching the GVA-minireplicon by agroinfiltration
      delivery resulted in a strong RNA silencing response. In light of this finding,
      we produced transgenic Nicotiana benthamiana plants expressing the GVA
      minireplicon, which displayed phenotypes that could be attributed to reproducibly
      and consistently activate post-transcriptional gene silencing (PTGS). These
      included: (i) low accumulation of the minireplicon-derived transgene; (ii) low
      GFP expression that was increased upon agroinfiltration delivery of viral
      suppressors of silencing; and (iii) resistance against GVA infection, which was
      found in 60%, and in 90-95%, of T1 and T2 progenies, respectively. A grafting
      assay revealed that non-silenced scions exhibited GVA resistance when they were
      grafted onto silenced rootstocks, suggesting transmission of RNA silencing from
      silenced rootstocks to non-silenced scions. Despite being extremely resistant to
      GVA infection, the transgenic plants were susceptible to the closely related
      vitivirus, GVB. Furthermore, infection of the silenced plants with GVB or Potato
      virus Y (PVY) resulted in suppression of the GVA-specific defense. From these
      data we conclude that GVA-minireplicon-mediated RNA silencing provides an
      important and efficient approach for consistent activation of PTGS that can be
      used for controlling grapevine viruses. However, application of this strategy for
      virus resistance necessitates consideration of possible infection by other
      viruses.

PMID- 18821076
TI  - Cloning and characterization of the inulinase gene from a marine yeast Pichia
      guilliermondii and its expression in Pichia pastoris.
AB  - The extracellular inulinase structural gene was isolated from the genomic DNA of
      the marine yeast Pichia guilliermondii strain 1 by PCR. The gene had an open
      reading frame of 1,542 bp long encoding an inulinase. The coding region of the
      gene was not interrupted by any intron. It encoded 514 amino acid residues of a
      protein with a putative signal peptide of 18 amino acids and the calculated
      molecular mass of 58.04 kDa. The protein sequence deduced from the inulinase
      structural gene contained the inulinase consensus sequences (WMNXPNGL) and
      (RDPKVF). It also had ten conserved putative N-glycosylation sites. The inulinase
      from P. guilliermondii strain 1 was found to be closely related to that from
      Kluyveromyces marxianus. The inulinase gene without the signal sequence was
      subcloned into pPICZalphaA expression vector and expressed in Pichia pastoris X
      33. The expressed fusion protein was analyzed by SDS-PAGE and western blotting
      and a specific band with molecular mass of about 60 kDa was found. Enzyme
      activity assay verified the recombinant protein as an inulinase. A maximum
      activity of 58.7 +/- 0.12 U/ml was obtained from the culture supernatant of P.
      pastoris X-33 harboring the inulinase gene. A large amount of monosaccharides,
      disaccharides and oligosaccharides were detected after the hydrolysis of inulin
      with the crude recombinant inulinase.

PMID- 18821077
TI  - Efficacy of computer aided analysis in detection of significant coronary artery
      stenosis in cardiac using dual source computed tomography.
AB  - OBJECTIVE: To analyze the diagnostic efficacy of computer aided analysis of
      relevant coronary artery stenosis using dual source computed tomography (DSCT).
      METHODS: In a larger scale study patients scheduled for conventional coronary
      angiography (CA) were additionally examined with DSCT. Based on a 13-segment
      model 30 CT scans of this study population were analyzed for significant stenosis
      using conventional 3D charts (3D) as well as a specialized cardiac analysis tool
      (CAT). Diagnostic accuracy and time to diagnosis was recorded for each vessel
      separately as well as the three readers' confidence. RESULTS: With severe
      coronary artery calcifications, 53 false interpretations of segments were found
      for the total of 390 coronary segments analyzed. 3D and CAT analysis showed a
      Sensitivity, Specificity, PPV and NPV of 0.59, 0.91, 0.57, 0.92 and 0.57, 0.92,
      0.56, 0.92, respectively. No significant differences in diagnostic accuracy could
      be found between 3D and CAT (P = 0.1667). 3D took a mean of 5.2 min (3-10 min).
      With CAT a mean time of 8.2 min (4-12 min) was needed. No significant inter
      reader time differences (P = 0.4954) and no significant confidence level
      differences were found between readers and analyzes. CONCLUSION: CAT of the
      coronary tree shows comparable accuracy to manual 3D analysis but needs
      improvements concerning coronary tree segmentation times.

PMID- 18821078
TI  - Adjudicating rights or analyzing interests: ethicists' role in the debate over
      conscience in clinical practice.
AB  - The analysis of a dispute can focus on either interests, rights, or power.
      Commentators often frame the conflict over conscience in clinical practice as a
      dispute between a patient's right to legally available medical treatment and a
      clinician's right to refuse to provide interventions the clinician finds morally
      objectionable. Multiple sources of unresolvable moral disagreement make
      resolution in these terms unlikely. One should instead focus on the parties'
      interests and the different ways in which the health care delivery system can
      accommodate them. In the specific case of pharmacists refusing to dispense
      emergency contraception, alternative systems such as advanced prescription,
      pharmacist provision, and over-the-counter sales may better reconcile the
      client's interest in preventing unintended pregnancy and the pharmacist's
      interest in not contravening his or her conscience. Within such an analysis, the
      ethicist's role becomes identifying and clarifying the parties' morally relevant
      interests.

PMID- 18821079
TI  - 16th Symposium on the Treatment of Parkinson's Disease, September 15, 2007,
      Tokyo, Japan. Preface.

PMID- 18821080
TI  - Movement disorder emergencies.
AB  - Movement disorder emergencies include any movement disorder which evolves over
      hours to days, in which failure to appropriately diagnose and manage can result
      in patient morbidity or mortality. It is crucial that doctors recognize these
      emergencies with accuracy and speed by obtaining the proper history and by being
      familiar with the phenomenology of frequently encountered movements. These
      disorders will be discussed based on the most common associated involuntary
      movement, either parkinsonism, dystonia, chorea, tics or myoclonus, and, when
      available, review the workup and treatment options based on the current
      literature.

PMID- 18821081
TI  - Dopamine dysregulation syndrome. Hypothetical application of reward system
      stimulation for the treatment of anhedonia in Parkinson's disease patients.
AB  - The management of motor symptoms in Parkinson's disease (PD), although imperfect,
      has already been standardized. However, patients often spend their time idly
      despite improvement in the elemental motor symptoms. The main cause of this may
      be anhedonia. Dopamine dysregulation syndrome (DDS) is a troublesome condition
      that can occur as a complication of dopamine replacement therapy in PD. As
      anhedonia and DDS may be converse syndromes in PD patients, it is very important
      to overcome anhedonia to improve patients' quality of life. In this article, the
      author proposes the possibility of stimulating patients' desire to participate in
      physical activity via the incentive of a reward system. Understanding the
      mechanism of DDS may help in the development of this type of approach.

PMID- 18821082
TI  - Substrates for normal gait and pathophysiology of gait disturbances with respect
      to the basal ganglia dysfunction.
AB  - In this review, we have tried to elucidate substrates for the execution of normal
      gait and to understand pathophysiological mechanisms of gait failure in basal
      ganglia dysfunctions. In Parkinson's disease, volitional and emotional
      expressions of movement processes are seriously affected in addition to the
      disturbance of automatic movement processes, such as adjustment of postural
      muscle tone before gait initiation and rhythmic limb movements during walking.
      These patients also suffer from muscle tone rigidity and postural instability,
      which may also cause reduced walking capabilities in adapting to various
      environments. Neurophysiological and clinical studies have suggested the
      importance of basal ganglia connections with the cerebral cortex and limbic
      system in the expression of volitional and emotional behaviors. Here we
      hypothesize a crucial role played by the basal ganglia-brainstem system in the
      integrative control of muscle tone and locomotion. The hypothetical model may
      provide a rational explanation for the role of the basal ganglia in the control
      of volitional and automatic aspects of movements. Moreover, it might also be
      beneficial for understanding pathophysiological mechanisms of basal ganglia
      movement disorders. A part of this hypothesis has been supported by studies
      utilizing a constructive simulation engineering technique that clearly shows that
      an appropriate level of postural muscle tone and proper acquisition and
      utilization of sensory information are essential to maintain adaptable bodily
      functions for the full execution of bipedal gait. In conclusion, we suggest that
      the major substrates for supporting bipedal posture and executing bipedal gait
      are 1) fine neural networks such as the cortico-basal ganglia loop and basal
      ganglia-brainstem system, 2) fine musculoskeletal structures with adequately
      developed (postural) muscle tone, and 3) proper sensory processing. It follows
      that any dysfunction of the above sensorimotor integration processes would result
      in gait disturbance.

PMID- 18821083
TI  - Deep brain stimulation for parkinsonian gait disorders.
AB  - The cardinal motor manifestation of Parkinson's disease (PD) is being treated
      with greater and greater efficacy with both newer medications as well as both
      subthalamic nucleus (STN) and globus pallidus internus (GPI) deep brain
      stimulation (DBS). The burden of disease is shifting towards the non-dopaminergic
      disease manifestations including gait and posture. Based on evidence in the
      literature and in animal models, recent trials are underway to examine the
      effects of pedunculopontine nucleus DBS on the treatment of parkinsonian gait
      disorder. We review the rationale behind this treatment and the status of the
      current trials.

PMID- 18821084
TI  - Levodopa-induced dyskinesias and their management.
AB  - This paper reviews the epidemiology, pathophysiology, clinical features and
      rationale for managing dyskinesias associated with Parkinson's disease. These are
      a common clinical problem occurring in up to 90% of patients and more frequently
      affect those with early-onset. Dyskinesias have a negative impact on quality of
      life and are an important cause of disability. Their precise etiology is still
      poorly understood, although it is recognized that dopaminergic pre-synaptic and
      post-synaptic mechanisms are involved together with extra-dopaminergic factors.
      The phenomenology of dyskinesias encompasses a variable mixture of two prevalent
      features: dystonia and chorea. We have studied their time course following a
      single acute levodopa challenge and have found that dystonia occurs throughout
      the duration of the on period, whereas choreiform movements occur only at the
      peak of therapeutic dopaminergic motor responses. This allows a schematic
      relationship to be drawn between a short duration motor response and the
      occurrence of dystonia and chorea. There is currently no satisfactory treatment
      for dyskinesias. Managing the therapeutic window does not provide an adequate
      solution due to the appearance of a dyskinesia threshold dose that narrows the
      therapeutic margin. High frequency stimulation of the subthalamic nucleus
      probably has some specific anti-dyskinetic action, but is limited by the small
      number of patients who are candidates for this treatment. Research efforts are
      currently focused on the development of specific anti-dyskinetic medications.
      Their availability will certainly change the current clinical practice and will
      widen again the therapeutic window of dopaminergic medications that has now
      become too narrow.

PMID- 18821085
TI  - Therapeutic strategies to prevent motor complications in Parkinson's disease.
AB  - Dopaminergic treatment of Parkinson's disease (PD) leads to significant
      improvement in Parkinsonian features; however, the treatment response is hampered
      by the appearance of motor complications, including dyskinesias and motor
      fluctuations. These motor complications have a significant negative impact on
      quality-of-life. Therapeutic strategies using different types and timing of
      dopaminergic therapy may influence the emergence of motor complications. While
      sustained release preparations of levodopa have not shown benefit over immediate
      release preparations, the early combination of a dopamine agonist with levodopa
      appears to reduce the onset of motor fluctuations. An even larger body of
      evidence has found that initiating treatment with a dopamine receptor agonist (as
      compared to immediate release levodopa) is associated with a reduction in motor
      fluctuations, particularly dyskinesias. These data have led to evidence-based
      medicine evaluations indicating that the use of dopamine agonists is efficacious
      and clinically useful for the prevention of motor complications.

PMID- 18821086
TI  - Evaluation of ELISA in the serodiagnosis of bovine farcy.
AB  - Mycobacterium farcinogenes is the causal agent of bovine farcy, a chronic
      infectious disease of zebu cattle in some parts of tropical Africa. Whole cell
      homologous antigen of M. farcinogenes was used in the standardization and
      evaluation of an enzyme linked immunosorbent assay (ELISA) for the detection of
      circulating antibodies against bovine farcy using sera from confirmed bovine
      farcy and from bovine farcy-free cattle. The cut-off optical density (OD) value
      was decided at 1.8 using filter 405 nm after one hour of incubation at 37 degrees
      C. Accordingly, 115 out of 124 (92.7%) serum samples from clinically proven
      bovine farcy cattle were reported sero-positive. Sera from cattle infected with
      M. avium and M. paratuberculosis revealed OD value <1.8, indicating the
      differential diagnostic ability of M. farcinogenes antigen. Our test sensitivity
      was 92.7% and specificity was 97%, therefore could be routinely employed to
      support early clinical diagnosis, epidemiological surveys and for screening
      animals before exportation to farcy-free regions.

PMID- 18821087
TI  - Oral micro-organisms in the etiology of cancer.
AB  - We present a novel concept on carcinogenesis mediated by oral microbiota. Oral
      micro-organisms are capable of metabolizing alcohol to acetaldehyde. This finding
      casts light on the observed association between poor oral hygiene and oral
      cancer. Ethanol, as such, is not carcinogenic, but its first metabolite
      acetaldehyde is indisputably carcinogenic. Several gastro-intestinal microbial
      species possess the enzyme alcohol dehydrogenase (ADH), which is also the enzyme
      responsible for alcohol metabolism in the liver. In oral microbiota, we observed
      that species such as the ubiquitous viridans streptococci and Candida also
      possess ADH. Ethanol can be detected in the mouth hours after the consumption of
      alcoholic beverages. Patients with poor oral health status have shown higher
      salivary acetaldehyde concentrations than those with better oral health. It is
      thus understandable that ADH-containing micro-organisms in the mouth present a
      risk for carcinogenic acetaldehyde production, with subsequent potential for the
      development of oral cancer, particularly among heavy drinkers. In this article,
      we briefly review this area of investigation and conclude by highlighting some
      future possibilities for the control of carcinogenesis.

PMID- 18821088
TI  - Social economic costs and health-related quality of life in patients with
      amyotrophic lateral sclerosis in Spain.
AB  - Amyotrophic lateral sclerosis (ALS) is a process that leads to the functional
      disability of the individual in a relatively short period of time, with a very
      important limitation of autonomy and affecting the quality of life. We wished to
      determine the economic burden (direct and indirect costs), as well as health
      related quality of life (HRQoL) in patients with ALS in Spain. A cross-sectional
      study was carried out on 63 patients with ALS during 2004. A retrospective
      assessment of the use of resources was obtained through questionnaires completed
      by the patients and/or the patients' caregivers. The approach used was a cost-of
      illness study based on a societal perspective. We assessed the HRQoL with the EQ
      5D. Mean annual cost per patient with ALS was euro36,194. The most important
      categories of costs were informal care, early retirement, medications, and
      orthopaedic devices. The mean EQ-5D index score was 0.18 and the mean EQ-5D VAS
      score was 29. Considerations of the costs related to caregiving to cope with the
      patients' disabilities, as well as the high indirect costs resulting from early
      retirement in patients with ALS, should become a priority for health authorities
      in Spain. The patients' HRQoL was very low and substantially influenced by the
      degree of severity of ALS.

PMID- 18821090
TI  - A novel dynamic heterogeneous phase polymerization reaction for poly-hemoglobin
      with narrow molecular weight distribution.
AB  - A dynamic heterogeneous phase polymerization reaction is found to be efficient
      for controllable cross-link of hemoglobin with glutaraldehyde. The selective
      absorption of the immobile phase and asymmetry of protein concentration leads to
      narrowness of the molecular weight distribution and lowness of the average
      molecular weight. Using this method, 53% of hemoglobin obtained is intermolecular
      cross-linked with 12 molecular equivalents of glutaraldehyde. The majority of
      poly-hemoglobins is in the range of 128 kD to 258 kD.

PMID- 18821091
TI  - Excretions of urinary albumin and various proteins increase in hypertension.
AB  - AIMS: Hypertension causes proteinuria and is an important factor in the progress
      of renal dysfunction. Increases in various proteins in urine are caused by
      malfunction of the glomerulus and the renal tubules. In the present study, the
      effects of hypertension on urinary excretion levels of various proteins were
      investigated to show the tubular cell malfunction in hypertensive patients.
      METHODS AND SUBJECTS: The subjects included 55 non-diabetic hypertensive patients
      without previous treatment and 42 normotensive individuals without
      microalbuminuria. Total urinary protein/creatinine ratio was measured, and
      urinary proteins were analyzed by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis (SDS-PAGE). FINDINGS: Total urinary protein/creatinine ratio was
      higher in hypertensive patients than in normotensive individuals (122.0+/-11.0
      vs. 60.6+/-3.1 mg/gCr; p<0.001). SDS-PAGE resolved 15 protein fractions from the
      urine of both groups. Thirteen fractions were more intensely stained in samples
      from the hypertensive than from the normotensive. Two fractions did not differ
      between the groups. Hypertension increased the urinary excretion of various
      proteins including proteins of less than 40 kDa, called tubular proteins, in
      addition to albumin. CONCLUSIONS: Hypertension differently influenced the
      excretion of each urinary protein fraction. Tubular malfunction should be
      considered in hypertensive patients in addition to glomerular malfunction.

PMID- 18821092
TI  - A comparison of hormone therapies on the urinary excretion of prostacyclin and
      thromboxane A2.
AB  - OBJECTIVE: To evaluate the effect of estradiol, estradiol and norethisterone
      acetate (NETA), raloxifene and tibolone on the prostacyclin (PGI(2))/thromboxane
      A2 (TxA(2)) ratio in postmenopausal women after 8 weeks of treatment. DESIGN:
      This was a randomized, double-blind, cross-over study. Each patient took 8-week
      courses of estradiol 2 mg, estradiol 2 mg + NETA 1 mg, tibolone 2.5 mg, and
      raloxifene 60 mg; there was an 8-week placebo wash-out between each different
      intervention. All volunteers took all four treatment options and were randomized
      to one of three possible sequences. Urine was collected and frozen at each visit.
      Urinary metabolites of PGI(2) and TxA(2) were then assessed at the end of the
      study. RESULTS: The ratio of PGI(2)/TxA(2) was significantly increased for
      raloxifene. No other treatments showed statistically significant changes.
      CONCLUSIONS: The relationship between cardiovascular risk and hormone replacement
      therapy remains poorly understood. Raloxifene may have additional
      cardioprotective effects that the other treatments did not demonstrate, and none
      of the treatments statistically worsened the PGI(2)/TxA(2) ratio. This ratio may
      be under-utilized as a marker of net effect on cardiovascular health, but more
      research is needed to link it to health outcomes.

PMID- 18821093
TI  - Usefulness of 13C-methacetin breath test in liver function testing in Amanita
      phalloides poisoning; breast feeding woman case.
AB  - INTRODUCTION: Mortality from ingestion of the mushroom Amanita phalloides still
      remains as high as 8-10%. In critical patients, liver dialysis can bridge the
      patient to liver transplantation, which may be a lifesaving procedure. We report
      the use of 13C-methacetin breath test (13C-MBT) in monitoring hepatic function in
      a case of A. phalloides poisoning. CASE REPORT: A 33-year-old woman ate mushrooms
      that she had picked. After 8 h, she developed nausea and vomiting, abdominal
      cramps, and diarrhea, which lasted for another 24 h. On the third day, features
      of liver injury were seen. Pharmacologic therapy failed and she underwent liver
      dialysis on days 4 and 5. A 13C-MBT was used to evaluate hepatic functional
      reserve before the first and after the second dialysis. A liver transplantation
      on day 6 was successful. DISCUSSION: The breath test results showed that at 40
      min after substrate ingestion the mean 13C-MBT cumulative oxidation percentage
      was 10.5 +/- 3.8% in healthy controls, whereas in our patient this parameter
      decreased from 0.09% on the fourth day to 0.02% on the fifth day. CONCLUSIONS:
      13C-MBT is a simple, non-invasive diagnostic tool which may be useful as a
      predictor of outcome and as a marker of the severity of liver damage.

PMID- 18821094
TI  - Oxcarbazepine-induced Drug Reaction with Eosinophilia and Systemic Symptoms
      (DRESS).
AB  - This is an image and brief case report of a 13-year-old boy who presented with
      severe rash and systemic symptoms after starting oxcarbazepine. The patient was
      diagnosed and treated for Drug Reaction with Eosinophilia and Systemic Symptoms
      (DRESS), a syndrome of fever, rash, and internal organ involvement secondary to
      medication administration. The image illustrates the rash seen with this drug
      reaction. The report is followed by a brief review of anticonvulsant
      hypersensitivity syndrome and DRESS.

PMID- 18821095
TI  - Lithium poisoning: is determination of the red blood cell lithium concentration
      useful?
AB  - INTRODUCTION: Despite a narrow therapeutic index, lithium remains a cornerstone
      for the treatment of bipolar disease. As lithium poisoning may result in life
      threatening neurotoxicity, measurement of the lithium concentration is mandatory
      in drug monitoring as well as for the diagnosis and prognostic evaluation of
      lithium poisoning. However, toxic symptoms do not always correlate with plasma
      concentrations. Therefore, more reliable indicators have been proposed, including
      measurement of the red blood cell (RBC) lithium concentration and the RBC-to
      plasma lithium ratio. PLASMA AND RBC LITHIUM CONCENTRATIONS: Few studies have
      reviewed the relative utility of these measurements both in monitoring therapy
      and in poisoning, and they have involved only small numbers of subjects.
      Moreover, factors influencing plasma and RBC lithium concentrations are numerous,
      including gender, age, dosage, treatment duration, co-medications, and underlying
      diseases. In treated patients, investigated using in vivo magnetic resonance
      spectroscopy, there is a significant correlation between plasma and brain lithium
      concentrations in steady-state conditions. In contrast, lithium transport across
      erythrocytes markedly differs from its transport into the central nervous system,
      questioning the relevance of measuring the RBC lithium concentration. In poisoned
      patients, plasma and RBC lithium concentrations follow a parallel decline
      irrespective of the type of poisoning. CONCLUSIONS: Based on present evidence,
      measurement of the RBC lithium concentration and the calculation of the RBC-to
      plasma lithium ratio offer no important clinical advantage over the measurement
      of the plasma lithium concentration, which remains the most important variable to
      monitor in lithium-treated or lithium-poisoned patients.

PMID- 18821096
TI  - Mechanical loading effects on isthmic spondylolytic lumbar segment: finite
      element modelling using a personalised geometry.
AB  - Biomechanics of the isthmic spondylolysis was investigated by using a nonlinear
      3D-finite element model (FEM). A personalised in vivo pediatric geometry of L5-S1
      low-grade spondylolisthesis patient was used to develop a L5-pelvis motion
      segment model that took into consideration vertebrae, disc and ligaments. The
      stress distribution in the affected motion segment under axial force only, and
      for a combination of flexion and extension was evaluated. Predicted results
      showed that, under all loading conditions, stresses were much higher on the
      pedicle and in the dorsal wall of the pars interarticularis due to the abnormal
      geometry which is consistent with clinical observations.

PMID- 18821098
TI  - The effects of perceived parenting style on the propensity for illicit drug use:
      the importance of parental warmth and control.
AB  - INTRODUCTION AND AIMS: Research in adolescents has shown that parental warmth and
      control are important factors in drug use. The present study focused upon
      investigating perceived parental warmth and control in a sample of post
      adolescent ecstasy/polydrug users, and investigating their relationship to
      severity of drug use. DESIGN AND METHODS: A total of 128 (65 male)
      ecstasy/polydrug users, 51 (17 male), cannabis-only users and 54 (13 male) non
      users were recruited from a university population. All participants completed the
      parenting styles and drug use questionnaires. RESULTS: Compared to non-users, a
      greater proportion of ecstasy/polydrug users characterised their parents' style
      as neglectful. The modal style endorsed by non-users was authoritative. Those who
      rated their parents' style as authoritative had significantly lower lifetime
      consumption and average dose of ecstasy relative to those describing their
      parents as neglectful. Again, relative to those describing their parents as
      neglectful, participants from authoritarian backgrounds had significantly smaller
      lifetime consumption of ecstasy and cocaine and significantly smaller average
      doses of cannabis, ecstasy and cocaine. Contrary to expectation, there was no
      significant association between perceived parental warmth and the severity of
      ecstasy use. DISCUSSION AND CONCLUSIONS: The present study is, to our knowledge,
      the first to quantify drug use, and relate it to perceived parental practices in
      a post-adolescent sample of ecstasy/polydrug users. The results provide further
      support for the relationship between perceived parental control and drug use.

PMID- 18821099
TI  - Glutathione diminishes tributyltin- and  dibutyltin-induced loss of lytic
      function in  human natural killer cells.
AB  - This study investigated whether reduced glutathione (GSH) was able to alter the
      negative effects of tributyltin (TBT) or dibutyltin (DBT) on the lytic function
      of human natural killer (NK) cells. NK cells are an initial immune defense
      against the development of tumors or viral infections. TBT and DBT are widespread
      environmental contaminants, due to their various industrial applications. Both
      TBT and DBT have been shown to decrease the ability of NK cells to lyse tumor
      cells (lytic function). The results indicated that the presence of GSH during the
      exposure of NK cells to TBT or DBT diminished the negative effect of the butyltin
      on the lytic function of NK cells. This suggests that the interaction of TBT and
      DBT with functionally relevant sulfhydryl groups in NK cells may be part of the
      mechanism by which they decrease NK lytic function.

PMID- 18821100
TI  - Drug-induced hyperbilirubinemia and the clinical influencing factors.
AB  - Hyperbilirubinemia may accompany harmful effects such as jaundice, brain
      dysfunction, and pharmacokinetic alterations of drugs. Clinical drugs are the
      important causes of hyperbilirubinemia, especially for patients with certain
      pathologic conditions or with genetic variations. This article reviews
      hyperbilirubinemic pathophysiology with respect to the effects of clinical drugs.
      In addition, this review introduces a new formula that may be utilized to
      estimate the annual occurrences of drug-induced hyperbilirubinemia in a hospital.
      Variations in the genes of UDP-glucuronosyltransferases, organic anion
      transporting polypeptides and multidrug resistance proteins are the predisposing
      factors for drug-induced hyperbilirubinemia; therefore, their genetic and ethnic
      polymorphisms are discussed.

PMID- 18821101
TI  - Tobacco use among South Asians: results of a community-university collaborative
      study.
AB  - OBJECTIVE: Although South Asians (individuals from India, Pakistan, Sri Lanka,
      Bangladesh, Nepal, Bhutan, and the Maldives) are the third largest Asian group in
      the USA, relatively little data are available to document their use of tobacco.
      We collected data from a community sample of 344 South Asian adults to assess
      rates of smokeless tobacco product use and smoking and examine demographic
      predictors of use. DESIGN: Non-random sample; cross-sectional survey. RESULTS:
      Close to a third of the sample (28%) reported current use of smokeless tobacco
      products. In multivariate analyses, gender and ethnicity were significant
      predictors of use of smokeless tobacco products. Men and Bangladeshis were more
      likely to use smokeless tobacco. The overall rate of daily cigarette/bidi smoking
      observed in our sample (9%) was similar to that observed in the population of
      California (10%); however, the rates among men (19%) and some ethnic subgroups
      (16% for Pakistanis) were significantly higher. Gender, ethnicity and years in
      the USA emerged as significant predictors of daily smoking with men and
      Pakistanis being significantly more likely to smoke. Length of stay in the USA
      was inversely related to daily smoking. CONCLUSION: These findings emphasize the
      need to disaggregate data for South Asians and suggest that tobacco control
      interventions should target specific segments of the population (men,
      Bangladeshis, Pakistanis). Interventions to decrease use of smokeless tobacco
      products are especially warranted for South Asians.

PMID- 18821102
TI  - Semi-empirical stochastic model of aerosol bolus dispersion in the human lung.
AB  - Aerosol bolus dispersion, that is, the broadening of an inhaled narrow aerosol
      bolus upon exhalation, was simulated by Monte Carlo methods using a stochastic,
      asymmetric morphometric model of the human lung. Physical mechanisms considered
      to contribute to bolus dispersion were (1) axial diffusion in conductive airways,
      approximated by effective diffusivities, (2) convective mixing at airway
      bifurcation sites, (3) differences in inspiratory and expiratory velocity
      profiles, (4) mixing with residual air in alveoli, and (5) inhomogeneous
      ventilation of the lung lobes due to asymmetric flow spitting at bifurcations and
      asymmetric and asynchronous filling of the five lung lobes. Theoretical
      predictions of the bolus dispersion model were compared to experimental data for
      79 healthy volunteers, which provide detailed information on statistical bolus
      parameters (half-width, standard deviation, skewness, and mode shift) and total
      bolus deposition as a function of the depth of bolus penetration into the airway
      system. Predicted bolus dispersion and deposition data show excellent agreement
      with the published experimental data, suggesting that axial diffusion in
      conductive airways and convective mixing in alveoli, resulting in irreversible
      particle transport, are the major determinants of bolus dispersion. The
      variability and asymmetry of the branching airway network, leading to asymmetric
      flow splitting at airway bifurcations, greatly enhances the effect of
      irreversibility and the resulting dispersion of the inhaled bolus.

PMID- 18821103
TI  - A study on vitamin D and vitamin A in milk and edible oils available in the
      United Arab Emirates.
AB  - Two high-performance liquid chromatography methods have been validated for the
      determination of vitamin D and vitamin A in milk and edible oils. The percentage
      recovery of vitamin D added to milk ranged from 89% to 105%, with the
      repeatability relative standard deviation ranging from 2.78% to 6.11%. Its
      recovery in oil samples ranged from 90% to 102%, with the repeatability relative
      standard deviation ranging from 3.97% to 7.54%. The average recovery of vitamin A
      added to milk was found to be 98.7%. Analytical data for vitamin D in different
      brands of milk and milk products in the market samples of the United Arab
      Emirates indicate that 87% of samples contain vitamin D with 39% of samples
      within the acceptable range (0.8-1.2 microg/100 ml), where as 31% were found to
      be under-fortified and 30% were over-fortified. Analytical data for vitamin D in
      edible oils confirm a large variation. All milk samples analyzed contain less
      than 55 microg/100 ml vitamin A.

PMID- 18821106
TI  - Cost analysis of direct versus indirect and individual versus group modes of
      manual-based speech-and-language therapy for primary school-age children with
      primary language impairment.
AB  - BACKGROUND: The study is the first within trial cost analysis of direct versus
      indirect and individual versus group modes of speech-and-language therapy for
      children with primary language impairment. AIMS: To compare the short-run
      resource consequences of the four interventions alongside the effects achieved
      measured by standardized scores on a test of expressive and receptive language.
      METHODS & PROCEDURES: The study design was a cost analysis integrated within a
      randomized controlled trial using a 2x2 factorial design (direct/indirect versus
      individual/group therapy) together with a control group that received usual
      levels of community-based speech-and-language therapy. Research interventions
      were delivered in school settings in Scotland, UK. Children aged between 6 and 11
      years, attending a mainstream school, with standard scores on the Clinical
      Evaluation of Language Fundamentals (CELF-III(UK)) of less than -1.25 standard
      deviation (SD) (receptive and/or expressive) and non-verbal IQ on the Wechsler
      Abbreviated Scale of Intelligence (WASI) above 75, and no reported hearing loss,
      no moderate/severe articulation/phonology/dysfluency problems or otherwise
      requiring individual work with a speech-and-language therapist. The intervention
      involved speech-and-language therapists and speech-and-language therapy
      assistants working with individual children or small groups of children. A
      therapy manual was constructed to assist the choice of procedures and activities
      for intervention. The cost analysis focused on the salary and travel costs
      associated with each mode of intervention. The cumulative distribution of total
      costs arising from the time of randomization to post-intervention assessment was
      estimated. Arithmetic mean costs were compared and reported with their 95%
      confidence intervals. OUTCOMES & RESULTS: The results of the intention-to-treat
      analysis revealed that there were no significant post-intervention differences
      between direct and indirect modes of therapy, or between individual and group
      modes on any of the primary language outcome measures. The cost analysis
      identified indirect therapy, particularly indirect group therapy, as the least
      costly of the intervention modes with direct individual therapy as the most
      costly option. The programme cost of providing therapy in practice over 30 weeks
      for children could represent between 30% and 75% of the total gross revenue spend
      in primary school per pupil, depending on the choice of assistant led group
      therapy or therapist-led individual therapy. CONCLUSIONS & IMPLICATIONS: This
      study suggests that speech-and-language therapy assistants can act as effective
      surrogates for speech-and-language therapists in delivering cost-effective
      services to children with primary language impairment. The resource gains from
      adopting a group-based approach may ensure that effective therapy is provided to
      more children in a more efficient way.

PMID- 18821107
TI  - The Peer Attitudes Toward Children who Stutter (PATCS) scale: an evaluation of
      validity, reliability and the negativity of attitudes.
AB  - BACKGROUND: Persistent calls for school-based education about stuttering
      necessitate a better understanding of peer attitudes toward children who stutter
      and a means to measure outcomes of such educational interventions. Langevin and
      Hagler in 2004 developed the Peer Attitudes Toward Children who Stutter scale
      (PATCS) to address these needs and gave preliminary evidence of reliability and
      construct validity. AIMS: To examine further the psychometric properties of PATCS
      and to examine the negativity of attitudes. METHODS & PROCEDURES: PATCS was
      administered to 760 Canadian children in grades 3-6. Measures included
      reliability, a confirmatory factor analysis (CFA), a known groups analysis,
      convergent validity with the Pro-Victim Scale of Rigby and Slee, and the
      negativity of attitudes. OUTCOMES & RESULTS: PATCS appears to tap a second-order
      general attitude factor and three first-order factors representing the constructs
      of Positive Social Distance (PSD), Social Pressure (SP), and Verbal Interaction
      (VI). In the known groups analysis, participants who had contact with someone who
      stutters had higher scores (more positive attitudes) than those who had not, and
      girls had higher scores than boys. PATCS correlated moderately (0.43, p<0.01)
      with the Pro-Victim scale. Finally, one-fifth (21.7%) of participants had scores
      that were somewhat to very negative. CONCLUSIONS & IMPLICATIONS: Results provide
      evidence of the validity and reliability of PATCS and confirm the need for school
      based education about stuttering. The PSD and SP factors suggest that education
      include discussions about (1) similarities and differences among children who do
      and do not stutter in order to increase acceptance, and (2) making personal
      choices and handling peer pressure in thinking about children who stutter. The VI
      factor suggests that open discussion about stuttering may alleviate frustration
      experienced by listeners and provide the opportunity to give strategies for
      responding appropriately. Results also suggest that education involve contact
      with a person who stutters.

PMID- 18821108
TI  - Cleft audit protocol for speech (CAPS-A): a comprehensive training package for
      speech analysis.
AB  - BACKGROUND: The previous literature has largely focused on speech analysis
      systems and ignored process issues, such as the nature of adequate speech
      samples, data acquisition, recording and playback. Although there has been
      recognition of the need for training on tools used in speech analysis associated
      with cleft palate, little attention has been paid to this issue. AIMS: To design,
      execute, and evaluate a training programme for speech and language therapists on
      the systematic and reliable use of the Cleft Audit Protocol for Speech-Augmented
      (CAPS-A), addressing issues of standardized speech samples, data acquisition,
      recording, playback, and listening guidelines. METHODS & PROCEDURES: Thirty-six
      specialist speech and language therapists undertook the training programme over
      four days. This consisted of two days' training on the CAPS-A tool followed by a
      third day, making independent ratings and transcriptions on ten new cases which
      had been previously recorded during routine audit data collection. This task was
      repeated on day 4, a minimum of one month later. Ratings were made using the CAPS
      A record form with the CAPS-A definition table. An analysis was made of the
      speech and language therapists' CAPS-A ratings at occasion 1 and occasion 2 and
      the intra- and inter-rater reliability calculated. OUTCOMES & RESULTS: Trained
      therapists showed consistency in individual judgements on specific sections of
      the tool. Intraclass correlation coefficients were calculated for each section
      with good agreement on eight of 13 sections. There were only fair levels of
      agreement on anterior oral cleft speech characteristics, non-cleft
      errors/immaturities and voice. This was explained, at least in part, by their low
      prevalence which affects the calculation of the intraclass correlation
      coefficient statistic. CONCLUSIONS & IMPLICATIONS: Speech and language therapists
      benefited from training on the CAPS-A, focusing on specific aspects of speech
      using definitions of parameters and scalar points, in order to apply the tool
      systematically and reliably. Ratings are enhanced by ensuring a high degree of
      attention to the nature of the data, standardizing the speech sample, data
      acquisition, the listening process together with the use of high-quality
      recording and playback equipment. In addition, a method is proposed for
      maintaining listening skills following training as part of an individual's
      continuing education.

PMID- 18821109
TI  - Untrained listeners' ratings of speech disorders in a group with cleft palate: a
      comparison with speech and language pathologists' ratings.
AB  - BACKGROUND: Hypernasal resonance, audible nasal air emission and/or nasal
      turbulence, and articulation errors are typical speech disorders associated with
      the speech of children with cleft lip and palate. Several studies indicate that
      hypernasal resonance tends to be perceived negatively by listeners. Most
      perceptual studies of speech disorders related to cleft palate are carried out
      with speech and language pathologists as listeners, whereas only a few studies
      have been conducted to explore how judgements by untrained listeners compare with
      expert assessments. These types of studies can be used to determine whether
      children for whom speech and language pathologists recommend intervention have a
      significant speech deviance that is also detected by untrained listeners. AIMS:
      To compare ratings by untrained listeners with ratings by speech and language
      pathologists for cleft palate speech. METHODS & PROCEDURES: An assessment form
      for untrained listeners was developed using statements and a five-point scale.
      The assessment form was tailored to facilitate comparison with expert judgements.
      Twenty-eight untrained listeners assessed the speech of 26 speakers with cleft
      palate and ten speakers without cleft in a comparison group. This assessment was
      compared with the joint assessment of two expert speech and language
      pathologists. OUTCOMES & RESULTS: Listener groups generally agreed on which
      speakers were nasal. The untrained listeners detected hyper- and hyponasality
      when it was present in speech and considered moderate to severe hypernasality to
      be serious enough to call for intervention. The expert listeners assessed audible
      nasal air emission and/or nasal turbulence to be present in twice as many
      speakers as the untrained listeners who were much less sensitive to audible nasal
      air emission and/or nasal turbulence. CONCLUSIONS & IMPLICATIONS: The results of
      untrained listeners' ratings in this study in the main confirm the ratings of
      speech and language pathologists and show that cleft palate speech disorders may
      have an impact in the everyday life of the speaker.

PMID- 18821110
TI  - Unhelpful thoughts and beliefs linked to social anxiety in stuttering:
      development of a measure.
AB  - BACKGROUND: Those who stutter have a proclivity to social anxiety. Yet, to date,
      there is no comprehensive measure of thoughts and beliefs about stuttering that
      represent the cognitions associated with that anxiety. AIMS: The present paper
      describes the development of a measure to assess unhelpful thoughts and beliefs
      about stuttering. METHODS & PROCEDURES: The Unhelpful Thoughts and Beliefs about
      Stuttering (UTBAS) self-report measure contains 66 items that assess the
      frequency of unhelpful thoughts and beliefs. Items were constructed from a
      comprehensive file audit of all stuttering cases seen in a cognitive-behavior
      therapy based treatment programme over a ten-year period. OUTCOMES & RESULTS:
      Preliminary investigations indicate that the UTBAS has high levels of test-retest
      reliability (r = 0.89) and internal consistency (Chronbach's alpha = 0.98). It
      has good known-groups validity, being able to discriminate between stuttering and
      non-stuttering participants on items that contain no reference to stuttering
      [t(38) = 8.06, p<0.0001], with a large effect size (d = 2.3). It has good
      convergent validity (r = 0.53-0.72) and discriminant validity (r = 0.24-0.27).
      The UTBAS sensitivity to change was supported by improvements in thoughts and
      beliefs related to social anxiety following cognitive-behavioural treatment for
      anxiety in stuttering [t(25) = 10.13, p<0.0001]. The effect size was large (d =
      2.5). CONCLUSIONS & IMPLICATIONS: Implications for the use of the UTBAS as an
      outcome measure and a clinical tool are discussed, along with the potential value
      of the UTBAS to explore the well-documented social anxiety experienced by those
      who stutter.

PMID- 18821111
TI  - Speech technology-based assessment of phoneme intelligibility in dysarthria.
AB  - BACKGROUND: Currently, clinicians mainly rely on perceptual judgements to assess
      intelligibility of dysarthric speech. Although often highly reliable, this
      procedure is subjective with a lot of intrinsic variables. Therefore, certain
      benefits can be expected from a speech technology-based intelligibility
      assessment. Previous attempts to develop an automated intelligibility assessment
      mainly relied on automatic speech recognition (ASR) systems that were trained to
      recognize the speech of persons without known impairments. In this paper
      automatic speech alignment (ASA) systems are used instead. In addition, previous
      attempts only made use of phonemic features (PMF). However, since articulation is
      an important contributing factor to intelligibility of dysarthric speech and
      since phonological features (PLF) are shared by multiple phonemes, phonological
      features may be more appropriate to characterize and identify dysarthric
      phonemes. AIMS: To investigate the reliability of objective phoneme
      intelligibility scores obtained by three types of intelligibility models: models
      using only phonemic features (yielded by an automated speech aligner) (PMF
      models), models using only phonological features (PLF models), and models using a
      combination of phonemic and phonological features (PMF + PLF models). METHODS &
      PROCEDURES: Correlations were calculated between the objective phoneme
      intelligibility scores of 60 dysarthric speakers and the corresponding perceptual
      phoneme intelligibility scores obtained by a standardized perceptual phoneme
      intelligibility assessment. OUTCOMES & RESULTS: The correlations between the
      objective and perceptual intelligibility scores range from 0.793 for the PMF
      models, over 0.828 for PLF models to 0.943 for PMF + PLF models. The features
      selected to obtain such high correlations can be divided into six main subgroups:
      (1) vowel-related phonemic and phonological features, (2) lateral-related
      features, (3) silence-related features, (4) fricative-related features, (5) velar
      related features and (6) plosive-related features. CONCLUSIONS & IMPLICATIONS:
      The phoneme intelligibility scores of dysarthric speakers obtained by the three
      investigated intelligibility model types are reliable. The highest correlation
      between the perceptual and objective intelligibility scores was found for models
      combining phonemic and phonological features. The intelligibility scoring system
      is now ready to be implemented in a clinical tool.

PMID- 18821112
TI  - Gesture and speech integration: an exploratory study of a man with aphasia.
AB  - BACKGROUND: In order to comprehend fully a speaker's intention in everyday
      communication, information is integrated from multiple sources, including gesture
      and speech. There are no published studies that have explored the impact of
      aphasia on iconic co-speech gesture and speech integration. AIMS: To explore the
      impact of aphasia on co-speech gesture and speech integration in one participant
      with aphasia and 20 age-matched control participants. METHODS & PROCEDURES: The
      participant with aphasia and 20 control participants watched video vignettes of
      people producing 21 verb phrases in three different conditions, verbal only (V),
      gesture only (G), and verbal gesture combined (VG). Participants were required to
      select a corresponding picture from one of four alternatives: integration target,
      a verbal-only match, a gesture-only match, and an unrelated foil. The probability
      of choosing the integration target in the VG that goes beyond what is expected
      from the probabilities of choosing the integration target in V and G was referred
      to as multi-modal gain (MMG). OUTCOMES & RESULTS: The participant with aphasia
      obtained a significantly lower multi-modal gain score than the control
      participants (p<0.05). Error analysis indicated that in speech and gesture
      integration tasks, the participant with aphasia relied on gesture in order to
      decode the message, whereas the control participants relied on speech in order to
      decode the message. Further analysis of the speech-only and gesture-only tasks
      indicated that the participant with aphasia had intact gesture comprehension but
      impaired spoken word comprehension. CONCLUSIONS & IMPLICATIONS: The results
      confirm findings by Records ( 1994 ) that reported that impaired verbal
      comprehension leads to a greater reliance on gesture to decode messages.
      Moreover, multi-modal integration of information from speech and iconic gesture
      can be impaired in aphasia. The findings highlight the need for further
      exploration of the impact of aphasia on gesture and speech integration.

PMID- 18821113
TI  - Delivering the Lee Silverman Voice Treatment (LSVT) by web camera: a feasibility
      study.
AB  - BACKGROUND: Speech disorders are a feature of Parkinson's disease, typically
      worsening as the disease progresses. The Lee Silverman Voice Treatment (LSVT) was
      developed to address these difficulties. It targets vocal loudness as a means of
      increasing vocal effort and improving coordination across the subsystems of
      speech. AIMS: Currently LSVT is not widely available, and there are practical
      difficulties associated with the delivery of an intensive treatment in an
      environment of resource constraints in the National Health Service (NHS).
      Delivery of LSVT over the World-Wide Web may address some of these difficulties.
      METHODS & PROCEDURES: A feasibility study is reported in which three individuals
      with speech disorders resulting from Parkinson's disease received LSVT over the
      Internet, using broadband connection and a web camera. Participants were seen
      face to face for every fourth session in order to build a personal relationship,
      measure vocal sound pressure level (SPL) during treatment, and to review and
      prepare homework tasks. All other sessions were delivered over the Internet.
      OUTCOMES & RESULTS: Broadly similar treatment gains were found between
      individuals treated over the Internet and those treated face to face. Gains were
      maintained or improved at an assessment two months after the treatment.
      CONCLUSIONS & IMPLICATIONS: This study demonstrates that delivery of LSVT over
      the Internet is feasible, and that a larger trial would be appropriate to
      establish cost and treatment effectiveness.

PMID- 18821114
TI  - Deaf teenagers with cochlear implants in conversation with hearing peers.
AB  - BACKGROUND: This study investigates the use of requests for clarification in
      conversations between teenagers with a cochlear implant (CI) and hearing peers.
      So far very few studies have focused on conversational abilities in children with
      CI. AIMS: The aim was to explore co-construction of dialogue in a referential
      communication task and the participation of the teenagers with CI in comparison
      with individually matched hearing children and teenagers (HC) by studying the use
      of requests for clarification. METHODS & PROCEDURES: Sixteen conversational pairs
      participated: eight pairs consisting of a child with CI and his/her hearing
      conversational partner (CIP); and eight pairs consisting of an HC and a
      conversational partner (HCP). The conversational pairs were videotaped while
      carrying out a referential communication task requiring the description of two
      sets of pictures depicting faces. The dialogues were transcribed and analysed
      with respect to the number of words and turns, the time it took for each pair to
      complete the tasks, and the occurrence and different types of requests for
      clarification that were used in each type of conversational pair and in each type
      of dialogue. OUTCOMES & RESULTS: The main finding was that the teenagers with CI
      produced significantly more requests for clarification than the HCs. The most
      frequently used type of request for clarification in all dialogues was request
      for confirmation of new information. Furthermore, there was a trend for the
      teenagers with CI to use this type of request more often than the HC. In
      contrast, the teenagers with CI used significantly fewer requests for
      confirmation of already given information and fewer requests for elaboration than
      the HC. CONCLUSIONS & IMPLICATIONS: The deaf teenagers with CI in the study seem
      to be equally collaborative and responsible conversational partners as the
      hearing teenagers. The interpretation is that certain conditions in this study
      facilitate their participation in conversation. Such conditions might be a calm
      environment, a task that is structured and without time limits and that the
      partner is well known to the teenager with CI.

PMID- 18821115
TI  - Optimizing speech production in the ventilator-assisted individual following
      cervical spinal cord injury: a preliminary investigation.
AB  - BACKGROUND: Mechanical ventilation is commonly used during the acute management
      of cervical spinal cord injury, and is required on an ongoing basis in the
      majority of patients with injuries at or above C3. However, to date there have
      been limited systematic investigations of the options available to improve speech
      while ventilator-assisted post-cervical spinal cord injury. AIMS: To provide
      preliminary evidence of any benefits gained through the addition of positive end
      expiratory pressure (PEEP) and/or a tracheostomy speech valve to the condition of
      leak speech. METHODS & PROCEDURES: Speech production in the three conditions was
      compared in two ventilator-assisted participants using a series of instrumental
      and perceptual speech measures. OUTCOMES & RESULTS: The addition of PEEP or the
      use of a speech valve resulted in speech that was superior to leak speech for
      both participants; however, individual variation was present. CONCLUSIONS &
      IMPLICATIONS: Leak speech alone or with the addition of PEEP or a tracheostomy
      speech valve can facilitate functional communication for the ventilated patient,
      though PEEP and valve speech were found to be superior in the current study.
      These findings will be of assistance for clinicians counselling the growing
      population of patients who may require tracheostomy positive pressure ventilation
      long-term regarding communication options.

PMID- 18821116
TI  - Evaluative expression in deaf children's written narratives.
AB  - BACKGROUND: Deaf children vary in the use of and proficiency in signed language.
      The majority of studies on writing skills of children who are deaf did not assess
      deaf children's proficiency in signed language and/or grouped together deaf
      children with varying sign language skills. AIMS: Adopting a bimodal bilingual
      perspective, we examined evaluative expression, an important narrative tool in
      both oral/written languages and signed languages, in narratives written in Dutch
      by deaf children who are proficient in Sign Language of the Netherlands (SLN) and
      deaf children who are low-proficient in SLN, and hearing monolingual and
      bilingual children. We hypothesized that deaf children who are proficient in
      signed language use their knowledge of evaluative expression in signed language
      to enrich their narratives in written Dutch, and more so than deaf children who
      are low-proficient in signed language and hearing monolingual and bilingual
      children. METHODS & PROCEDURES: We examined the use of eight different evaluative
      devices in narratives written by deaf proficiently and low-proficiently signing
      children, and hearing monolingual and bilingual children. Narratives were also
      examined for morpho-syntactic errors and use of complex sentences. OUTCOMES &
      RESULTS: The results show that proficiently signing deaf children's narratives
      contain more evaluative devices that enrich the referential structure of the
      narrative than narratives of low-proficiently signing deaf children, and hearing
      bilingual and monolingual children. CONCLUSIONS & IMPLICATIONS: We propose that
      proficiently signing deaf children use their knowledge of SLN to convey
      evaluation in their written narratives, and thus have an advantage in enriching
      their narratives. This study also shows that in order to gain insight into deaf
      people's writing, it is important to take variations in sign language proficiency
      into account.

PMID- 18821117
TI  - Review of visual speech perception by hearing and hearing-impaired people:
      clinical implications.
AB  - BACKGROUND: Speech perception is often considered specific to the auditory
      modality, despite convincing evidence that speech processing is bimodal. The
      theoretical and clinical roles of speech-reading for speech perception, however,
      have received little attention in speech-language therapy. AIMS: The role of
      speech-read information for speech perception is evaluated by considering
      evidence from hearing infants and adults, people with speech disorders, and those
      born profoundly hearing impaired. METHODS & PROCEDURES: Research studies are
      evaluated for evidence on lip-reading for speech perception: the mandatory role
      of speech-reading for hearing adults' perception of the McGurk effect and hearing
      infants' awareness of the congruence between lip movements and speech sounds;
      brain neuroimaging studies of speech-read and heard speech perception; the speech
      reading abilities of people with disordered speech; and the phonological coding
      abilities of people with profound pre-lingual hearing loss. Theories of
      multimodal speech perception are explained. MAIN CONTRIBUTIONS: Five pieces of
      evidence indicate that speech-reading is an integral part of speech processing.
      Hearing people's perception of speech is influenced by speech-read cues, and
      those speech-read cues cannot be ignored. Infants are aware that lip movements
      and speech sounds match from soon after birth and by four months of age have
      language specific speech-reading skills. Studies of brain activity show that the
      brain processes speech-read and heard speech similarly. Some children and adults
      with speech disorders are reported to rely less on speech-read cues than people
      without speech disorders, and children who are profoundly hearing impaired from
      birth have concepts of rhyme, match homophones, and can repeat and spell nonsense
      words. CONCLUSIONS & IMPLICATIONS: Speech-reading, a mandatory part of speech
      perception, should be appropriately assessed and be considered when developing
      strategies for speech and language intervention.

PMID- 18821118
TI  - Cantharidin treatment for recalcitrant facial flat warts: a preliminary study.
AB  - BACKGROUND: Topical cantharidin has been reported to be effective and safe in the
      treatment of cutaneous warts but it has not previously been used for the
      treatment of facial flat warts. OBJECTIVE: To evaluate the efficacy and safety of
      topical cantharidin in the treatment of recalcitrant facial flat warts. METHODS:
      A total of 15 consecutive patients with recalcitrant facial flat warts were
      enrolled in this study. Patients having warts near the eye region were excluded
      from the study. Cantharidin 0.7% solution was applied to treat a maximum of five
      lesions per session. Repeat therapy was performed at 3-week intervals. Assessment
      for response and the occurrence of side effects was performed after every session
      until clinical cure or up to a maximum of 16 weeks. RESULTS: Of the study
      population, patients had 8.2 +/- 4.37 lesions before the treatment. The average
      duration of lesions was 12.6 +/- 6.75 months. All the patients were clinically
      cured within 16 weeks and the number of required sessions for complete clearance
      was 2.6 +/- 1.18. Cantharidin therapy was well tolerated, with mild adverse
      events related to skin. CONCLUSION: Cantharidin is safe and effective when
      applied to flat warts without occlusion for 4-6 hours every 3 weeks till clear.

PMID- 18821119
TI  - A pramoxine-based anti-itch lotion is more effective than a control lotion for
      the treatment of uremic pruritus in adult hemodialysis patients.
AB  - OBJECTIVE: The objective of this study was to evaluate the efficacy of a
      commercially available anti-itch lotion containing 1% pramoxine hydrochloride
      versus control lotion in the treatment of uremic pruritus in adult hemodialysis
      patients. METHODS: This was a randomized, double-blind, controlled comparative
      trial set in a community hemodialysis center. The study population comprised 28
      individuals (mean age 53.5) with moderate to severe uremic pruritus who had been
      receiving hemodialysis for at least 3 months. All participants were recruited
      from one community hemodialysis center. Topical anti-itch lotion containing 1%
      pramoxine was applied twice daily to all affected areas of pruritus for 4 weeks.
      The main outcome measure was a reduction in itch intensity. Secondary outcomes
      included increases in the investigator's global assessment and improvement in
      skin hydration. RESULTS: There was a 61% decrease in itch intensity in the
      treatment group, whereas a 12% reduction in itch intensity was observed in the
      control group. The rate of decline in itching was also greater in the treatment
      arm versus the control arm. No significant differences were displayed in other
      studied disease-related variables. CONCLUSION: Our study shows that individuals
      using pramoxine 1% lotion experienced a reduction in pruritus to a greater degree
      than those using the control lotion. This safe, convenient and effective topical
      lotion may potentially benefit the large number of patients affected by pruritus
      associated with end-stage renal disease.

PMID- 18821120
TI  - Microspheres with pH modulated release: design and characterization of
      formulation variables for colonic delivery.
AB  - The aim of this study was to design and develop microspheres of indomethacin with
      pH and transit time dependent release properties for achieving targeted delivery
      to the colon. Microspheres containing varying proportions of ethyl cellulose and
      Eudragit (L100 or S100) either alone or in combination were prepared using an oil
      in-oil emulsion-based solvent evaporation technique. System comprising of acetone
      (internal phase) and liquid paraffin (external phase) in the ratio of 1 : 1 and 1
      : 9 yielded microspheres with good physical properties (spherical and discrete),
      high drug loading (70-80%) and entrapment efficiency (70-85%). The lag time in
      the initial release depended on the proportion of pH-sensitive polymer Eudragit,
      while the duration of indomethacin release from microspheres was found to be
      directly proportional to proportion of the total polymer. Thus, a pH- and time
      modulated sigmoidal release pattern could be observed in optimized formulations
      with less than 10% drug release in 4-6 h followed by controlled release extending
      up to 14-16 h.

PMID- 18821121
TI  - Human herpesvirus 6 meningoradiculitis treated with intravenous immunoglobulin
      and valganciclovir.
AB  - Human herpesvirus 6 (HHV-6) is being increasingly associated with multiple
      neurological conditions. The authors report the case of a 26-year-old man with
      subacute meningoradiculitis initially treated with intravenous immunoglobulin.
      The cerebrospinal fluid (CSF) showed pleocytosis and polymerase chain reaction
      (PCR) was positive for HHV-6 type B DNA in the CSF and peripheral blood. He was
      subsequently treated with valganciclovir with near resolution of his symptoms.

PMID- 18821122
TI  - The importance of accurate site location for skinfold measurement.
AB  - We assessed the importance of accurate site location for skinfold measurement in
      ten healthy males in a cross-sectional quantitative study. Nine measurements, in
      a 1-cm grid pattern, centred on each of eight ISAK-specified skinfold sites, were
      taken three times at each grid point by each of two ISAK Level 4 practitioners
      using Harpenden skinfold callipers. The presence of significant systematic
      discrepancy between reliability measures of different skinfold sites and grid
      points for each of the two testers was determined using P-values. Effect sizes
      were calculated to show the magnitude of effects. Skinfolds taken at the eight
      peripheral grid points were generally different from the skinfolds taken at a
      central ISAK grid point and there was an effect by direction away from the
      central ISAK point (anterior, posterior, superior or inferior). The subscapular
      skinfold had the least number of differences (three) and the abdominal had the
      most (eight). All other skinfold sites showed some variation with most care
      needed in marking the biceps and triceps skinfold sites. Adherence to
      identifying, marking, and measuring at the defined site is essential.

PMID- 18821123
TI  - Antioxidant response and oxidative damage induced by a swimming session:
      influence of gender.
AB  - In this study, we examined oxidative stress after a swimming session, the
      responses of the antioxidant defences, and the influence of gender on these
      responses. Fifteen boys and eight girls participated voluntarily in the study.
      Plasma concentrations of 17-beta-estradiol, vitamin E, retinol, carotenes,
      ascorbate, malondialdehyde, and the carbonyl index were determined. Creatine
      kinase, gamma glutamyl transpeptidase, and lactate dehydrogenase activities, as
      well as glucose, urea, urate, cholesterol, and triglycerides, were determined in
      serum. Plasma concentrations of 17-beta-estradiol were higher in girls than in
      boys. Exercise increased plasma ascorbate both in boys and in girls.
      Malondialdehyde increased in boys but was maintained in girls after exercise.
      Creatine kinase values corrected for lean body mass were similar in boys and
      girls at baseline, but the post-exercise values in boys were higher than in
      girls. A positive correlation was observed in boys, but not in girls, between
      plasma malondialdehyde and creatine kinase corrected concentrations. Furthermore,
      a negative correlation was observed between the increase in circulating
      neutrophils and in creatine kinase activity in girls but not in boys. In
      conclusion, a swimming session induced higher muscular and oxidative damage in
      boys than in girls.

PMID- 18821124
TI  - Problem based practical  courses (PBPC) induce  self-directed structured 
      learning of practical skills.

PMID- 18821125
TI  - Promoting evidence based medicine in preclinical medical students via a federated
      literature search tool.
AB  - BACKGROUND: Medical educators are increasingly faced with directives to teach
      Evidence Based Medicine (EBM) skills. Because of its nature, integrating
      fundamental EBM educational content is a challenge in the preclinical years.
      AIMS: To analyse preclinical medical student user satisfaction and feedback
      regarding a clinical EBM search strategy. METHODS: The authors introduced a
      custom EBM search option with a self-contained education structure to first-year
      medical students. The implementation took advantage of a major curricular change
      towards case-based instruction. Medical student views and experiences were
      studied regarding the tool's convenience, problems and the degree to which they
      used it to answer questions raised by case-based instruction. RESULTS: Surveys
      were completed by 70% of the available first-year students. Student satisfaction
      and experiences were strongly positive towards the EBM strategy, especially of
      the tool's convenience and utility for answering issues raised during case-based
      learning sessions. About 90% of the students responded that the tool was easy to
      use, productive and accessed for half or more of their search needs. CONCLUSIONS:
      This study provides evidence that the integration of an educational EBM search
      tool can be positively received by preclinical medical students.

PMID- 18821126
TI  - The role of sterol rings and side chain on the structure and phase behaviour of
      sphingomyelin bilayers.
AB  - The role of the side chain of sterols and the sterol ring structure on the
      formation of ordered phases of the type observed in membrane rafts has been
      examined in aqueous dispersions of binary mixtures of sphingomyelin and
      androsterol. Comparisons have been made with binary systems of cholesterol,
      stigmasterol, beta-sitosterol, and ergosterol with either sphingomyelin or
      dipalmitoylphosphatidylcholine. Thermotropic phase behaviour and structure of the
      mixed aqueous dispersions were characterized by differential scanning
      calorimetry, synchrotron X-ray diffraction, freeze-fracture electron microscopy,
      and Fourier-transform infrared spectroscopy. We show that: (i) Androsterol is
      less efficient in promoting the formation of liquid-ordered phase than other
      naturally occurring sterols which possess a side chain, (ii) cholesterol is the
      most efficient sterol of those investigated in forming liquid-ordered phase,
      (iii) the molecular stoichiometry of egg sphingomyelin and androsterol in the
      liquid-ordered phase is about 2:1, and (iv) sphingomyelin can form more stable
      liquid-ordered phase than glycerophospholipid in binary systems containing
      androsterol.

PMID- 18821127
TI  - Optimization of chitosan succinate and chitosan phthalate microspheres for oral
      delivery of insulin using response surface methodology.
AB  - In the present study, a Box-Behnken experimental design was employed to
      statistically optimize the formulation parameters of chitosan phthalate and
      chitosan succinate microspheres preparation. These microspheres can be useful for
      oral insulin delivery system. The effects of three parameters namely polymer
      concentration, stirring speed and cross linking agent were studied. The fitted
      mathematical model allowed us to plot response surfaces curves and to determine
      optimal preparation conditions. Results clearly indicated that the crosslinking
      agent was the main factor influencing the insulin loading and releasing. The in
      vitro results indicated that chitosan succinate microspheres need high amount of
      crosslinking agent to control initial burst release compared to chitosan
      phthalate microspheres. The reason may be attributed that chitosan succinate is
      more hydrophilic than chitosan phthalate. The relative pharmacological efficacy
      for chitosan phthalate and chitosan succinate microspheres (18.66 +/- 3.84%,
      16.24 +/- 4%) was almost three-fold higher than the efficacy of the oral insulin
      administration (4.68 +/- 1.52%). These findings suggest that these microspheres
      are promising carrier for oral insulin delivery system.

PMID- 18821128
TI  - Determination of the mechanism of uptake of organic vapors by chitoasn.
AB  - It was of interest to investigate the possible interactions that might occur
      between chitosan and various compounds of different polarities using solvent
      vapor sorption and Fourier Transform Infrared Spectroscopy (FTIR). The sorption
      system was composed of a gas inlet, a 2 meter gas cell and a gas outlet. The
      experimental set up allowed quantification of the free vapor and therefore the
      amount of the sorbed vapor by chitosan powder. The BET equation was applied to
      the experimental data to obtain the apparent monolayer sorption capacity (Sm) and
      the parameter C, which is related to the heat of interaction. Results
      demonstrated that the surface areas obtained for chitosan from the BET analyses
      for heptane, 1,4-dioxane and methanol were 421, 379 and 58 m(2)/g, respectively.
      These values were extremely higher than the value obtained from nitrogen vapor
      adsorption isotherm (4.56 m(2)/g). The difference is attributed to the
      partitioning of these compounds into the chitosan particles. The large difference
      in the Sm values between the nonpolar (heptane and 1,4-dioxane) and the semipolar
      compounds (methanol) also suggested that the polarity of the solvent might have a
      significant effect on the partitioning of the these compounds into the chitosan
      particles. The results obtained from this study also confirmed what was
      previously described regarding the ability of chitosan to act as a 'fat magnet'
      or a 'fat sponge'.

PMID- 18821129
TI  - Solid surface chemical and physical effects on the adsorption of recombinant
      Factor VIII.
AB  - The adsorption of a recombinant Factor VIII to silica surfaces coated to present
      different hydrophilic/hydrophobic, electrostatic and steric characteristics was
      monitored in situ, with ellipsometry. rFVIII adsorption affinity was high for
      hydrophobic surfaces and hydrophilic, charged surfaces. A lower affinity was
      recorded between rFVIII and a neutral hydrophilic surface, with substantial
      reduction in rFVIII adsorption to electronically neutral surfaces presenting
      pendant poly[ethylene oxide] chains. We conclude that steric repulsion is a
      requirement for minimizing rFVIII adsorption at solid surfaces.

PMID- 18821130
TI  - Order of magnitude differences between methods for maintaining physiological
      17beta-oestradiol concentrations in ovariectomized rats.
AB  - The use of animal models, especially the rat, is crucial for elucidating the
      biological effects and mechanisms of the widely used hormone 17beta-oestradiol.
      Unfortunately, there is a lack of consensus on optimal means of obtaining and
      maintaining physiological 17beta-oestradiol concentrations in plasma and this may
      be the reason for the varying results in several studies, including the
      disagreement on whether 17beta-oestradiol is neuroprotective or not. Very few
      studies have been devoted to investigating the characteristics and biological
      relevance of different methods of 17beta-oestradiol administration. We therefore
      ovariectomized 75 Sprague-Dawley rats and, following a 2-week washout period,
      administered 17beta-oestradiol using three different methods; daily injections
      (10 microg 17beta-oestradiol/kg), slow-release pellets (0.25 mg 60 day-release
      pellets, 0.10 mg 90 day-release pellets) and silastic capsules (with/without
      washout periods) (silastic laboratory tubing, inner/outer diameter: 1.575/3.175
      mm, filled with 20 mm columns of 180 microg 17beta-oestradiol/mL sesame oil). A
      further 45 animals were used as ovariectomized and native controls studied in
      different parts of the oestrous cycle. Silastic capsules produced concentrations
      of 17beta-oestradiol within the physiological range 4-5 weeks independently of
      whether a prior washout period was included or not. The slow-release pellets,
      irrespective of dose or release period, resulted in initial concentrations an
      order of magnitude above physiological concentrations during the first 2 weeks
      followed by a substantial decrease. Daily injections resulted in increasing
      17beta-oestradiol concentrations, but within physiological levels. Silastic
      capsules are conveniently manufactured and used and are superior to pellets and
      injections in reliably producing long-term 17beta-oestradiol concentrations
      within the physiological range.

PMID- 18821131
TI  - High levels of serum antibodies to cell surface proteins of Helicobacter pullorum
      and Helicobacter pylori in hepatitis C virus-infected patients.

PMID- 18821132
TI  - Comparison of high-resolution magnification narrow-band imaging and white-light
      endoscopy in the prediction of histology in Barrett's oesophagus.
AB  - OBJECTIVE: To evaluate whether there is any appreciable difference in imaging
      characteristics between high-resolution magnification white-light endoscopy (WLE
      Z) and narrow-band imaging (NBI-Z) in Barrett's oesophagus (BE) and if this
      translates into superior prediction of histology. MATERIAL AND METHODS: This was
      a prospective single-centre study involving 21 patients (75 areas, corresponding
      NBI-Z and WLE-Z images) with BE. Mucosal patterns (pit pattern and microvascular
      morphology) were evaluated for their image quality on a visual analogue scale
      (VAS) of 1-10 by five expert endoscopists. The endoscopists then predicted
      mucosal morphology based on four subtypes which can be visualized in BE. Type A:
      round pits, regular microvasculature; type B: villous/ridge pits, regular
      microvasculature; type C: absent pits, regular microvasculature; type D:
      distorted pits, irregular microvasculature. The sensitivity (Sn), specificity
      (Sp), positive predictive value (PPV), negative predictive value (NPV) and
      accuracy (Acc) were then compared with the final histopathological analysis and
      the interobserver variability calculated. RESULTS: The overall pit and
      microvasculature quality was significantly higher for NBI-Z, pit: NBI-Z=6, WLE
      Z=4.5, p < 0.001; microvasculature: NBI-Z=7.3, WLE-Z=4.9, p < 0.001. This
      translated into a superior prediction of histology (Sn: NBI-Z: 88.9, WLE-Z: 71.9,
      p < 0.001). For the prediction of dysplasia, NBI-Z was superior to WLE-Z
      (chi(2)=10.3, p < 0.05). The overall kappa agreement among the five endoscopists
      for NBI-Z and WLE-Z, respectively, was 0.59 and 0.31 (p < 0.001). CONCLUSIONS:
      NBI-Z is superior to WLE-Z in the prediction of histology in BE, with good
      reproducibility. This novel imaging modality could be an important tool for
      surveillance of patients with BE.

PMID- 18821133
TI  - Staphylococci in primary skin and soft tissue infections in a Swedish county.
AB  - Patients with skin and soft tissue infections (SSTI) are frequently encountered
      in primary health care. The majority are uncomplicated and treated empirically by
      surgical incision and drainage and/or antibiotics. This strategy may risk
      delaying the detection of methicillin-resistant Staphylococcus aureus (MRSA),
      which, although still rare in Sweden, is increasingly being found in patients
      with SSTI. To avoid 'late detection' of MRSA, primary health care physicians in
      Kronoberg county, Sweden, were asked to perform a culture as soon as the
      patient's first visit. Samples from 175 patients with primary SSTI confirmed that
      S. aureus is the dominant pathogen. Two cases of MRSA were detected. Furthermore,
      isolates of S. aureus producing the Panton-Valentine leukocidin (PVL) toxin were
      more common among isolates from SSTI than among S. aureus from secondary
      infections. Finally, we confirmed the importance of the coagulase-negative
      staphylococcal species S. lugdunensis as a pathogen as it was isolated as the
      only pathogen in 10% of the skin and soft tissue samples.

PMID- 18821134
TI  - Doxycycline for nursing home acquired pneumonia (NHAP).

PMID- 18821135
TI  - Persistent Staphylococcus aureus bacteremia: incidence and outcome trends over
      time.
AB  - Persistent Staphylococcus aureus bacteremia (SAB-P) is well known but poorly
      delineated due to unclear definition. We retrospectively studied 78 patients with
      SAB-P using a stringent definition (bacteremia for > or = 7 d), in a single
      teaching hospital, during 1 January 2002 to 30 June 2003 and 1 November 2005 to
      31 December 2006 to determine whether the frequency, risk factors and outcome
      changed over time. SAB was encountered in 354 and 259 instances during the 2
      periods, respectively. Patients' characteristics changed with increasing organ
      dysfunction score (2.9+/-1.7 vs 3.4+/-1.4; p <0.001), patients with invasive
      devices (27.7% vs 41.3%; p=0.001), hemodialysis dependence (19.2% vs 27.8%;
      p=0.04), MRSA (50.8% vs 64.5%; p=0.001), and vancomycin treatment (57.9% vs
      67.2%; p=0.02). SAB-P frequency increased slightly (11.0% vs 15.1%). Risk
      (associated) factors for SAB-P (identified by logistic regression) were
      metastatic infection (OR=5.60; 95% CI 3.00 - 10.47), vancomycin treatment
      (OR=4.17; 95% CI 2.14 - 8.11), endovascular sources (OR=3.35; 95% CI 1.92 - 5.85)
      and diabetes (OR=2.14; 95% CI 1.26 - 3.64). SAB- and SAB-P-associated case
      fatality did not change (23.2% vs 18.5% and 25.6 vs 30.8%, respectively). All
      survivors ultimately achieved clearance. These findings suggest that patients
      with SAB are changing over time. Additionally, SAB-P frequency is higher than
      previously reported. SAB-P rise is probably due to increasing SAB, MRSA, and
      patients at risk for complications. Innovative approaches should target novel
      treatment modalities and risk reduction.

PMID- 18821136
TI  - Integrating research into practice: a challenge for local authority occupational
      therapy.
AB  - The aim of this qualitative study was to identify and analyse the experiences of
      Swedish local health authority occupational therapists with regard to their
      participation in, and the implementation of, research. Data were collected from
      three focus-group interviews, with five different occupational therapists in
      each. The interviews were taped and transcribed and thereafter analysed using
      broad coding. One core category-"feeling professionally competent"-emerged,
      comprising three subcategories: "perceiving congruence between research and
      practice", "having the necessary skills", and "making a contribution". Feeling
      professionally competent embraces the occupational therapists' definition and
      delimitation of their professional domain and the obligations related to this. It
      also embraces the perception of having the skills necessary for participating in
      research projects and implementing research findings in a scientific manner. The
      implementation of research was not only perceived as contributing to the
      knowledge base of the profession, but personal gains could also be made. The
      knowledge gained from this study can help in the development of strategies to
      promote the integration of research in local authority occupational therapy
      practice. This is necessary; otherwise the occupational therapy provided will be
      based on the knowledge and perceptions of individual professionals, rather than
      on state-of-the-art knowledge gained through research.

PMID- 18821137
TI  - Relationship between Tomm performance and PAI validity scales in a mixed clinical
      sample.
AB  - This study addressed the relationship between Personality Assessment Inventory
      (PAI) validity indicators and cognitive effort measures on the Test of Memory
      Malingering (TOMM). Significant correlations were found between TOMM and some PAI
      validity scales. Factor analysis results found separate cognitive and personality
      components, but the Negative Impression Management (NIM) scale, a measure of
      response bias, had factor loadings on both the cognitive and the personality
      components. Follow-up hierarchical multiple regression and t-test analysis
      generally confirmed this result, and found that NIM and the Infrequency (INF)
      scale have significant relationships with the TOMM. The results indicate that
      individuals with elevations on the PAI's INF and NIM scales often display
      decreased cognitive effort on the TOMM. The current results support the
      hypothesis that personality assessment validity indicators have a modest but
      significant relationship with poor cognitive effort.

PMID- 18821138
TI  - Interpreting the meaning of multiple symptom validity test failure.
AB  - While it is recommended that judgments regarding the credibility of test
      performance be based on the results of more than one effort indicator, and recent
      efforts have been made to improve interpretation of multiple effort test failure,
      the field currently lacks adequate guidelines for using multiple measures of
      effort in concert with one another. A total of 103 patients were referred for
      outpatient neuropsychological evaluation, which included multiple measures of
      negative response bias embedded in standard test batteries. Using any pairwise
      failure combination to predict diagnostic classification was superior
      (sensitivity = 83.8%, specificity = 93.9%, overall hit rate = 90.3%) to using any
      one test by itself and to using any three-test failure combination. Further, the
      results were comparable to the results of logistical regression analyses using
      the embedded indicators as continuous predictors. Given its parsimony and
      clinical utility, the pairwise failure model is therefore a recommended criterion
      for identifying non-credible performance; however, there are of course other
      important contextual factors and influences to consider, which are also
      discussed.

PMID- 18821139
TI  - Integrating patient empowerment as an essential characteristic of the discipline
      of general practice/family medicine.
AB  - BACKGROUND: Efforts to improve the quality of healthcare for patients with
      chronic conditions have resulted in growing evidence supporting the inclusion of
      patient empowerment as a key ingredient of care. In 2002, WONCA Europe issued the
      European Definition of General Practice/Family Medicine, which is currently
      considered the point of reference for European health institutions and general
      medical practice. Patient empowerment does not appear among the 11
      characteristics of the discipline. OBJECTIVES: The aim of this study is to show
      that many characteristics of general practice are already oriented towards
      patient empowerment. Therefore, promoting patient empowerment and self-management
      should be included as a characteristic of the discipline. METHODS: The following
      investigation was conducted: analysing the concept and approach to empowerment as
      applied to healthcare in the literature; examining whether aspects of empowerment
      are already part of general medical practice; and identifying reasons why the
      European definition of general practice/family medicine should contain
      empowerment as a characteristic of the discipline. RESULTS: General
      practice/family medicine is the most suitable setting for promoting patient
      empowerment, because many of its characteristics are already oriented towards
      encouraging it and because its widespread presence can ensure the generalization
      of empowerment promotion and self-management education to the totality of
      patients and communities. CONCLUSION: "Promoting patient empowerment and self
      management" should be considered one of the essential characteristics of general
      practice/family medicine and should be included in its definition.

PMID- 18821140
TI  - How to grade categories of evidence.

PMID- 18821141
TI  - Prolene: a novel, cheap, and effective material in dacryocystorhinostomy.
AB  - CONCLUSION: Prolene is cheap, effective, and readily available in almost all
      operating theaters. It might be used successfully in endoscopic
      dacryocystorhinostomy and is promising as an alternative to silicone stent
      intubations, especially in settings with limited resources. OBJECTIVE: To
      evaluate the clinical efficacy and results of stenting with polypropylene
      (Prolene; Ethicon, Inc.) suture material instead of silicone tube in endoscopic
      dacryocystorhinostomy. PATIENTS AND METHODS: Forty-two endoscopic
      dacryocystorhinostomy operations were performed in 36 patients (11 men and 25
      women; mean age 34.7 + or - 9.5 years, range 16-60 years) between 2007 and 2008.
      After creating an aperture in the medial wall of the lacrimal sac, 2/0 Prolene
      was inserted through the canaliculi into the sac. The Prolene was left in the
      lacrimal sac for 3 months. The patients were followed up for between 6 and 18
      months (mean 8.1 + or - 3.6 months). The improvement in the complaint of epiphora
      was grouped as very good, good, or no change. RESULTS: The improvement in 34 eyes
      (81%) was reported as very good, whereas improvement was noted as good in 5 eyes
      (11.9%), and there was no change in 3 eyes (7.1%). We observed granulation tissue
      formation around the Prolene in two patients.

PMID- 18821142
TI  - Open-label pilot trial of levetiracetam for cramps and spasticity in patients
      with motor neuron disease.
AB  - Cramps and spasticity impair quality of life and function in patients with motor
      neuron diseases, and there are no proven treatments for these problems. We
      conducted a pilot trial to determine if treatment with levetiracetam was
      associated with a reduction in cramp severity, cramp frequency, tonic or phasic
      spasticity. We used an open-label repeated measures pilot trial of 20 patients,
      comparing cramp and spasticity scores over a 3-month baseline versus nine months
      on treatment. Cramp and spasticity scores were stable over a 3-month baseline.
      Shortly after starting levetiracetam, there was a significant reduction in cramp
      severity and frequency, which persisted for the duration of this year-long study.
      There was also a reduction in phasic but not tonic spasticity. Levetiracetam was
      well tolerated. Our results justify a placebo-controlled study of levetiracetam
      for treatment of cramps and spasticity in patients with motor neuron diseases,
      and suggest that this can be accomplished with a small number of subjects
      followed for a short time.

PMID- 18821143
TI  - Metabolic syndrome and multiple organ damage in essential hypertension.
AB  - AIM: We investigated the prevalence of the metabolic syndrome (MS) in
      hypertensive patients categorized according to the number of markers of organ
      damage (OD) in order to assess the value of a systematic search for cardiac and
      extra-cardiac OD in the MS setting. METHODS: A total of 3119 untreated and
      treated essential hypertensives included in the Evaluation of Target Organ Damage
      in Hypertension (ETODH), an observational registry of hypertension-related OD,
      were considered for this analysis. All patients underwent extensive investigation
      for left ventricular hypertrophy (LVH) or LV concentric remodeling (cardiac OD),
      carotid plaques and/or intima-media thickening (vascular OD) and microalbuminuria
      (MA) and/or increased serum creatinine (renal OD). Subjects were classified as:
      positive for none (group 0), one (group I), two (group II) or three markers
      (group III) of OD. RESULTS: MS prevalence rates progressively rose across the
      groups stratified according to the OD score, reaching a 2.3-fold increase in
      group III compared with their MS counterparts in group 0. The distribution of
      subjects with and without the MS across the groups was 15% vs 29% (group 0), 32%
      vs 38% (group I), 39% vs 26% (group II) and 14% vs 7% (group III), respectively.
      Thus, subjects having two or three markers of OD were 53% among those with MS and
      33% (p<0.01) among those without it. CONCLUSION: Our findings indicate a strong
      association between the MS and OD by showing that a clustering of two or three
      markers of OD is the prevalent cardiovascular phenotype in MS hypertensives
      referred to a specialist center and call for a systematic evaluation of cardiac
      and extracardiac OD in this setting.

PMID- 18821144
TI  - Transforming growth factor beta1 T29C gene polymorphism and hypertension:
      relationship with cardiovascular and renal damage.
AB  - Distribution of T29C TGFbeta1 gene polymorphism was analysed in 260 hypertensive
      and 134 normotensive subjects. Circulating TGFbeta1 and procollagen type III
      levels, microalbuminuria, left ventricular geometry and function were evaluated
      in all the hypertensives subgrouped according to T29C TGFbeta1 gene polymorphism.
      Circulating TGFbeta1 by ELISA technique, procollagen type III by a specific
      radioimmunoassay, microalbuminuria by radioimmunoassay, left ventricular geometry
      and function by echocardiography were determined. All groups were comparable for
      gender, age and sex. Regarding T29C TGFbeta1 gene polymorphism, prevalence of TC
      or CC genotypes was significantly (p<0.05) higher in hypertensives than
      normotensives. TC and CC hypertensives were characterized by a higher prevalence
      of subjects with microalbuminuria (p<0.001 TC vs TT; p<0.05 CC vs TT), left
      ventricular hypertrophy (p<0.01 TC and CC vs TT), and by increased levels of
      procollagen type III (p<0.05 TC and CC vs TT). TC hypertensives were also
      characterized by a significant increase (p<0.05) of LVM and LVM/h(2.7 )and of
      urinary albumin excretion (p<0.05) values than those detectable in TT
      hypertensives. Our data suggest that T29C TGFbeta1 gene polymorphism was
      associated to clinical characteristics suitable to recognize hypertensives with a
      higher severity of hypertension.

PMID- 18821145
TI  - Toxicity from the recreational use of 1-benzylpiperazine.
AB  - AIM: This study describes the demographics and symptoms of patients, who
      presented to the Emergency Department (ED) in Christchurch, New Zealand, with
      toxicity from 1-benzylpiperazine (BZP)-based "party pills." BZP use has become
      widespread among the 16- to 30-year age group in New Zealand. This study explores
      the relationship between plasma BZP level and adverse effects experienced by
      users. The influence of ethanol co-ingestion was also studied. METHODS: From 1
      April 2005 to 1 July 2007, all BZP-related presentations to the ED were captured
      on a prospective data sheet. Patients were recruited to obtain plasma BZP levels,
      and these were correlated with the incidence of seizures and other symptoms.
      Coexistent ethanol use was also correlated with the frequency of seizures and
      other common BZP-induced symptoms. RESULTS: In total 178 presentations with BZP
      toxicity were recorded. BZP levels were measured in 96. Sixty-nine percent of
      patients co-ingested other substances, with the most common substance being
      ethanol. In patients who ingested BZP alone, increased plasma BZP levels were
      associated with increased seizure frequency. Ethanol co-ingestion reduced the
      incidence of seizures, but significantly increased the likelihood of confusion
      and agitation. CONCLUSIONS: Adverse effects from BZP commonly include confusion,
      agitation, vomiting, anxiety, and palpitations. There is strong evidence that
      higher plasma levels of BZP are associated with an increased incidence of
      seizures. Co-ingestion of ethanol increases the likelihood of common and
      distressing BZP-induced symptoms but reduces the incidence of BZP seizures.

PMID- 18821146
TI  - A mighty wind.

PMID- 18821147
TI  - CroFab reconstitution in various media: an in vitro solubility study.
AB  - BACKGROUND: We investigated the solubility of Crotalidae Polyvalent Ovine Immune
      Fab antivenom (CroFab, Savage Labs and Protherics Inc., Brentwood, TN, USA) in
      solutions not listed in the Food and Drug Administration (FDA)-approved product
      package insert. We also assessed whether adsorption to plastic tubing occurs with
      CroFab preparations. METHODS: Nine vials of expired CroFab were divided into
      three groups according to the solution used for reconstitution. Assignment to the
      solution groups of normal saline, lactated Ringer's solution, or half-normal
      saline (NS, LR, 1/2NS) was blinded. The antivenom was diluted to a final volume
      of 75 mL of test solution. Protein concentration was measured after
      reconstitution, after storage at 4-6 degrees C for 4 h, and after passage through
      plastic intravenous (IV) tubing. RESULTS: Higher measured protein yields were
      noted when half-normal saline was used in comparison with normal saline at each
      step of the study. Lactated Ringer's solution yielded higher protein
      concentrations than normal saline only at one out of the three measurement steps.
      There was no adsorption effect when CroFab was infused through plastic IV tubing.
      DISCUSSION: These data suggest that CroFab is slightly more soluble in the
      hypotonic solution we tested, and the amounts of measured antivenom did not
      diminish after 4 h of refrigeration or passage through plastic tubing.
      CONCLUSION: Our study may be of relevance when clinicians or pharmacists mix
      CroFab into non-standard solutions.

PMID- 18821148
TI  - The effect of ethyl pyruvate on dapsone-induced methemoglobinemia in rats.
AB  - INTRODUCTION: Dapsone induces methemoglobinemia by oxidant stress; ethyl pyruvate
      (EP) is an antioxidant and radical oxygen species scavenger. This study was
      conducted to evaluate the effect of EP on methemoglobinemia induced by dapsone.
      METHODS: Male Sprague-Dawley rats were divided into an EP group and a control
      group. Rats in the EP group were administered dapsone (40 mg/kg) via the stomach
      and then EP (40 mg/kg) was injected intraperitoneally. Rats in the control group
      were administered dapsone followed by Ringer's lactate solution. Methemoglobin
      concentrations were measured at 90, 180, and 360 min after dapsone
      administration. RESULTS: Methemoglobin concentrations were not different between
      time points in the control group. However, in the EP group, the methemoglobin
      concentrations were significantly lower than those of the control group at 90 and
      180 min, but this difference was no longer apparent at 360 min. CONCLUSION: A
      single intraperitoneal dose of EP was able to reduce methemoglobinemia induced by
      dapsone for a short period of time, but this effect was not sustained.

PMID- 18821149
TI  - Evaluation of the role of peroxisome proliferator-activated receptor alpha
      (PPARalpha) in mouse liver tumor induction by trichloroethylene and metabolites.
AB  - Trichloroethylene (TCE) is an industrial solvent and a widespread environmental
      contaminant. Induction of liver cancer in mice by TCE is thought to be mediated
      by two metabolites, dichloroacetate (DCA) and trichloroacetate (TCA), both of
      which are themselves mouse liver carcinogens. TCE, TCA, and DCA are relatively
      weak peroxisome proliferators (PP), a group of rodent hepatocarcinogens that
      activate a nuclear receptor, PP-activated receptor alpha (PPARalpha. The
      objective of this review is to assess the weight of evidence (WOE) that PPARalpha
      is or is not mechanistically involved in mouse liver tumor induction by TCE and
      metabolites. Based on similarities of TCE and TCA to typical PP, including dose
      response characteristics showing PPARalpha-dependent responses coincident with
      liver tumor induction and abolishment of TCE and TCA effects in PPARalpha-null
      mice, the WOE supports the hypothesis that PPARalpha plays a dominant role in TCE
      and TCA-induced hepatocarcinogenesis. Data indicates that the MOA for DCA tumor
      induction is PPARalpha-independent. Uncertainties remain regarding the genesis of
      the TCE-induced tumors. In contrast to the TCA-induced tumors, which have
      molecular features similar to those induced by typical PP, there is evidence,
      albeit weak, that TCE tumors arise by a mode of action (MOA) different from that
      of TCA tumors, based largely on dissimilarities in molecular markers found in TCE
      versus TCA-induced tumors. In summary, the WOE indicates that TCA-induced liver
      tumors arise by a PPARalpha-dependent MOA. Although the TCE MOA is likely
      dominated by a PPARalpha-dependent contribution from TCA, the contribution of a
      PPARalpha-independent MOA from DCA cannot be ruled out.

PMID- 18821150
TI  - Transdermal delivery of tadalafil. I. Effect of vehicles on skin permeation.
AB  - Transdermal delivery that avoids the presystemic disposition can provide an
      alternative to oral administration of tadalafil. Accordingly, the aim of this
      study was to select the best vehicle as the first step in optimization of
      tadalafil transdermal delivery. The vehicles were used neat or in selected binary
      combinations and were evaluated for drug solubilization and transdermal delivery.
      The drug solubility in pure vehicles were ranked as polyethylene glycol (PEG) 400
      > propylene glycol (PG) > ethanol > ethyl oleate (EO) > isopropyl myristate (IPM)
      > water. The solubility in binary systems containing ethanol at 2:1 ratios with
      EO or IPM was greater than that obtained with pure ethanol, EO, or IPM. This
      effect could be due to the cosolvency effect. The transdermal drug delivery from
      pure vehicles was ranked as IPM > EO > ethanol > PG > PEG > water. The delivery
      from binary mixtures of ethanol with either IPM or EO was higher than that
      obtained from pure solvents with the delivery increasing with increasing ethanol
      concentration in the mixtures. The delivery from binary mixtures was synergistic
      rather than additive. The study thus demonstrated a potential of tadalafil
      transdermal delivery. Binary combinations of ethanol with either IPM or EO
      provided the first step forward toward the development of transdermal delivery
      system for tadalafil.

PMID- 18821151
TI  - Preparation and evaluation of fast-disintegrating effervescent tablets of
      glibenclamide.
AB  - Fast-dissolving effervescent tablets (FETs) were prepared by the modification of
      nonreactive liquid-based wet granulation technique. Effervescent systems are not
      stable in the presence of trace amount of moisture, and elimination or
      inactivation of free water is the key to stability apart from manufacturing in
      controlled humidity environment. Our main objective of the project was to develop
      FETs of glibenclamide based on highly plastic granules that can be compressed at
      low pressure to form fast-melting pharmaceutical tablets. In this study, we have
      screened various acid and carbonate sources for the effervescent system. Citric
      acid was coated with plastic materials such as polyethylene glycol (PEG), which
      provide a physical barrier to the reaction. The inherent hygroscopic nature of
      PEG could decrease the affinity for moisture of effervescent mixtures and can
      provide a stabilizing effect. Sodium bicarbonate was blended with sugar alcohol
      like mannitol, which would give a protective coating. PEG 1000 melts at body
      temperature (approximately 37 degrees C) and thereby does not delay the reaction
      between the acid source and base. The present formulation using citric acid
      sodium bicarbonate and citric acid-sodium glycine carbonate tablet with PEG and
      mannitol was found to have better reaction properties and reaction stability than
      does the standard citric acid-sodium bicarbonate tablet. FETs of glibenclamide
      might aid in dissolution due to increase in microenvironmental pH around the
      granules and saliva. Sensory study on disintegration time and mouth feel
      attributes ranked the present formulation based on grittiness, chalkiness, and
      overall preference as best.

PMID- 18821152
TI  - Chitosan-based thermosensitive hydrogel containing liposomes for sustained
      delivery of cytarabine.
AB  - Sustained release thermosensitive solution containing cytarabine-loaded liposome
      delivery system offers the possibility of reduced dosing frequency and sustained
      drug action. Biodegradable and biocompatible chitosan-beta-glycerophosphate (C
      GP) thermosensitive solution having the property to gel at body temperature and
      to maintain its physical integrity for longer period of time was used. The C-GP
      solution containing cytarabine-loaded liposomes (CGPCLL) was studied, and the
      results showed that the cytarabine liposomes were capable of high encapsulation
      efficiency (85.2 +/- 2.58%) with the mean diameter of 220 +/- 6.9 nm of extruded
      cytarabine-loaded liposome. Furthermore, transmission electron microscopy showed
      spherical-shaped liposomes after extrusion with smooth surface. In vitro studies
      of CGPCLL in PBS buffer showed that this system can sustain release of
      encapsulated drug for more than 60 h compared with drug-loaded liposomal
      suspension (upto 48 h). Pharmacokinetic studies of CGPCLL resulted in higher
      t(1/2) (28.86 h) and AUC 2526.88 mug/mL h compared with cytarabine-loaded
      liposomal suspension (CLLS) and C-GP containing free cytarabine (CGPFC) in rats.
      CGPCLL was capable of sustaining the cytarabine release for more than 60 h in
      vivo compared with CLLS and CGPFC which showed maximum amount of drug release
      within 42 and 10 h, respectively. Thus, these results showed that the CGPCLL gels
      at body temperature and can sustain the delivery of cytarabine effectively.

PMID- 18821153
TI  - Development of glyburide fast-dissolving tablets based on the combined use of
      cyclodextrins and polymers.
AB  - Commercial tablets of glyburide exhibit unsatisfactory dissolution profiles and,
      consequently, problems of bioinequivalence and poor bioavailability. The aim of
      this work was to develop glyburide fast-dissolving tablets by exploiting the
      solubilizing effect of different cyclodextrins (CDs), alone or in combination
      with hydrophilic polymers. Drug-CD and drug-CD-polymer systems, prepared by
      different techniques, were characterized by differential scanning calorimetry
      (DSC), X-ray diffractometry, and Fourier transform infra-red (FT-IR)
      spectroscopy. Tablets containing binary and ternary systems were prepared by
      direct compression and evaluated for technological properties and dissolution
      behavior in comparison with a reference formulation containing the plain drug. A
      significant improvement of the drug dissolution profile was achieved from tablets
      containing drug-CD systems (coevaporated products doubled drug dissolution
      efficiency [DE]), but 100% drug dissolution was never reached. Better results
      were obtained with ternary systems. In particular, polyvinylpyrrolidone (PVP)
      emerged as the most effective polymer, and tablets with drug-PVP-hydroxypropyl
      betaCD coevaporated products showed the best dissolution profiles, reaching 100%
      dissolved drug within only 15 min.

PMID- 18821154
TI  - Preparation and characterization of spironolactone-loaded gelucire microparticles
      using spray-drying technique.
AB  - The basic objectives of this study were to prepare and characterize solid
      dispersions of poorly soluble drug spironolactone (SP) using gelucire carriers by
      spray-drying technique. The properties of the microparticles produced were
      studied by differential scanning calorimetry (DSC), scanning electron microscopy,
      saturation solubility, encapsulation efficiency, and dissolution studies. The
      absence of SP peaks in DSC profiles of microparticles suggests the transformation
      of crystalline SP into an amorphous form. The in vitro dissolution test showed a
      significant increase in the dissolution rate of microparticles as compared with
      pure SP and physical mixtures (PMs) of drug with gelucire carriers. Therefore,
      the dissolution rate of poorly water-soluble drug SP can be significantly
      enhanced by the preparation of solid dispersion using spray-drying technique.

PMID- 18821155
TI  - Does outdoor alcohol advertising around elementary schools vary by the ethnicity
      of students in the school?
AB  - OBJECTIVES: The objectives of this study were to determine: (1) if the number of
      outdoor alcohol advertisements around schools varied by ethnicity of students in
      the school; and (2) how the content of alcohol advertising around schools varied
      by the ethnicity of students in the school. METHODS: All outdoor alcohol
      advertisements within 1500 feet of 63 Chicago schools were documented and coded
      for content and theme. On average, the ethnic make-up of schools was 54.9%
      African American, 24.4% Hispanic, and 16.2% White; 79.7% of students were low
      SES. To compare the mean number and type of ads by ethnicity of the school,
      schools were coded by ethnicity (i.e., 20% or more Hispanic students compared
      with less than 20% Hispanic students). RESULTS: Youth attending schools with 20%
      or more Hispanic students were exposed to 6.5 times more alcohol advertising than
      students attending schools with less than 20% Hispanic students. Schools with 20%
      or more Hispanic students were also surrounded by more beer advertising and
      alcohol advertisements on bars and liquor stores. CONCLUSIONS: Alcohol
      advertising is more prevalent around schools with 20% or more Hispanic students.
      Policies should be considered to reduce the amount of alcohol advertising around
      schools.

PMID- 18821156
TI  - Implication of xanthine oxidase in muscle oxidative stress in COPD patients.
AB  - OBJECTIVE: The aim of this study was to determine the implication of xanthine
      oxidase (XO) in the exercise-induced muscle oxidative stress and muscle
      dysfunction of these patients. METHODS: A randomized, crossover and double-blind
      study was conducted in nine severe COPD patients, who performed a localized
      quadriceps endurance test after oral treatment with allopurinol, a XO inhibitor
      or placebo. Redox status was studied in arterial and venous femoral blood before
      and after the endurance test. RESULTS: In placebo condition, muscle exercise
      resulted in a significant increase in AOPP and isoprostanes, with a significant
      increase in the venoarterial difference (v-a) in isoprostanes after exercise as
      compared with before (p<0.05). In contrast, allopurinol treatment prevented the
      elevation in AOPP levels and v-a isoprostanes after exercise. However, no
      significant improvement in quadriceps muscle endurance was observed, but
      allopurinol treatment seemed to preserve muscle strength properties. CONCLUSION:
      This study demonstrates that XO is implicated in the exercise-induced muscle
      oxidative stress of COPD patients. Allopurinol administration seemed to improve
      only some muscle properties. Therefore other sources of muscle oxidative stress
      should be implicated in muscle dysfunction observed in these patients.

PMID- 18821157
TI  - Using telerehabilitation to assess apraxia of speech in adults.
AB  - BACKGROUND: Telerehabilitation is the remote delivery of rehabilitation services
      via information technology and telecommunication systems. There have been a
      number of studies that have used videoconferencing to assess speech and language
      skills in people with acquired neurogenic communication disorders. However, few
      studies have focused on cases of apraxia of speech. In order to perform
      accurately differential diagnosis via the telerehabilitation medium, it is
      important that validation of the assessment of apraxia of speech be established
      as part of the overall evidence base for telerehabilitation communication
      assessment protocols. AIMS: To determine if valid and reliable assessment of
      apraxia of speech using a standardized assessment tool was feasible via
      telerehabilitation. METHODS & PROCEDURES: Eleven participants with an acquired
      apraxia of speech were assessed simultaneously via telerehabilitation and face-to
      face methods on the Apraxia Battery for Adults - 2 (ABA-2). A custom-built
      telerehabilitation system developed at the University of Queensland enabled real
      time telerehabilitation assessment over a 128 kbit/s internet connection. Data
      analysis included tests of significant difference between raw scores using the
      Wilcoxon signed rank statistic and analysis of the degree of agreement between
      the two methods using weighted Kappa statistics. Inter- and intra-rater
      reliabilities were also examined for the telerehabilitation-led assessments.
      OUTCOMES & RESULTS: Results revealed no significant differences between the
      subtest scores of the ABA-2 obtained in the telerehabilitation and face-to-face
      test environments (p = 0.06-0.68). Weighted Kappa statistics indicated moderate
      to very good agreement (0.59-1.00) between the two environments for the subtests
      of the ABA-2. The reliability study was hampered by small sample size; however,
      the data were suggestive of reasonable reliability. Participants reported high
      overall satisfaction, comfort level, and audio and visual quality in the
      telerehabilitation environment. The speech-language pathologists (SLP) reported
      some difficulties assessing participants with severe apraxia of speech via the
      telerehabilitation system. CONCLUSIONS & IMPLICATIONS: This study suggests that
      valid assessment of apraxia of speech using the ABA-2 over the internet is
      feasible. The reliability study on the telerehabilitation assessments was
      encouraging with results suggesting that telerehabilitation assessment using the
      ABA-2 could be reliable. Findings from the participant satisfaction questionnaire
      were favourable. However, comments from the SLP suggested that participants
      exhibiting severe apraxia of speech might be better suited to face-to-face
      assessment. These findings may have implications for the development of evidence
      based guidelines for the use of telerehabilitation in the assessment of apraxia
      of speech. The authors propose that future research should include larger sample
      sizes with a range of participant severity levels and be conducted over higher
      bandwidth connections to explore further the validity and reliability of
      telerehabilitation assessment of apraxia of speech.

PMID- 18821158
TI  - Pragmatics fragmented: the factor structure of the Dutch children's communication
      checklist (CCC).
AB  - BACKGROUND: A number of disorders are associated with pragmatic difficulties.
      Instruments that can make subdivisions within the larger construct of pragmatics
      could be important tools for disentangling profiles of pragmatic difficulty in
      different disorders. The deficits underlying the observed pragmatic difficulties
      may be different for different disorders. AIMS: To study the construct validity
      of a pragmatic language questionnaire. METHOD & PROCEDURES: The construct of
      pragmatics is studied by applying exploratory factor analysis (EFA) and
      confirmatory factor analysis to the parent version of the Dutch Children's
      Communication Checklist (CCC; Bishop 1998 ). Parent ratings of 1589 typically
      developing children and 481 children with a clinical diagnosis were collected.
      Four different factor models derived from the original CCC scales and five
      different factor models based on EFA were compared with each other. The models
      were cross-validated. OUTCOMES & RESULTS: The EFA-derived models were
      substantively different from the originally proposed CCC factor structure. EFA
      models gave a slightly better fit than the models based on the original CCC
      scales, though neither provided a good fit to the parent data. Coherence seemed
      to be part of language form and not of pragmatics, which is in line with the
      adaptation of the CCC, the CCC-2 (Bishop 2003 ). Most pragmatic items clustered
      together in one factor and these pragmatic items also clustered with items
      related to social relationships and specific interests. CONCLUSIONS &
      IMPLICATIONS: The nine scales of the original CCC do not reflect the underlying
      factor structure. Therefore, scale composition may be improved on and scores on
      subscale level need to be interpreted cautiously. Therefore, in interpreting the
      CCC profiles, the overall measure might be more informative than the postulated
      subscales as more information is needed to determine which constructs the
      suggested subscales are actually measuring.

PMID- 18821159
TI  - Exploration of a 'double-jeopardy' hypothesis within working memory profiles for
      children with specific language impairment.
AB  - BACKGROUND: Children with specific language impairment (SLI) often experience
      difficulties in the recall and repetition of verbal information. Archibald and
      Gathercole (2006) suggested that children with SLI are vulnerable across two
      separate components of a tripartite model of working memory (Baddeley and Hitch
      1974). However, the hierarchical relationship between the 'slave' systems
      (temporary storage) and the central executive components places a particular
      challenge for interpreting working memory profiles within a tripartite model.
      AIMS: This study aimed to examine whether a 'double-jeopardy' assumption is
      compatible with a hierarchical relationship between the phonological loop and
      central executive components of the working memory model in children with SLI. If
      a strong double-jeopardy assumption is valid for children with SLI, it was
      predicted that raw scores of working memory tests thought to tap phonological
      loop and central executive components of tripartite working memory would be lower
      than the scores of children matched for chronological age and those of children
      matched for language level, according to independent sources of constraint. In
      contrast, a hierarchical relationship would imply that a weakness in a slave
      component of working memory (the phonological loop) would also constrain
      performance on tests tapping a super-ordinate component (central executive). This
      locus of constraint would predict that scores of children with SLI on working
      memory tests that tap the central executive would be weaker relative to the
      scores of chronological age-matched controls only. METHODS & PROCEDURES: Seven
      subtests of the Working Memory Test Battery for Children (Digit recall, Word
      recall, Non-word recall, Word matching, Listening recall, Backwards digit recall
      and Block recall; Pickering and Gathercole 2001) were administered to 14 children
      with SLI recruited via language resource bases and specialist schools, as well as
      two control groups matched on chronological age and vocabulary level,
      respectively. Mean group differences were ascertained by directly comparing raw
      scores on memory tests linked to different components of the tripartite model
      using a series of multivariate analyses. OUTCOMES & RESULTS: The majority of
      working memory scores of the SLI group were depressed relative to chronological
      age-matched controls, with the exception of spatial recall (block tapping) and
      word (order) matching tasks. Marked deficits in serial recall of words and digits
      were evident, with the SLI group scoring more poorly than the language-ability
      matched control group on these measures. Impairments of the SLI group on
      phonological loop tasks were robust, even when covariance with executive working
      memory scores was accounted for. There was no robust effect of group on complex
      working memory (central executive) tasks, despite a slight association between
      listening recall and phonological loop measures. CONCLUSIONS & IMPLICATIONS: A
      predominant feature of the working memory profile of SLI was a marked deficit on
      phonological loop tasks. Although scores on complex working memory tasks were
      also depressed, there was little evidence for a strong interpretation of double
      jeopardy within working memory profiles for these children, rather these findings
      were consistent with an interpretation of a constraint on phonological loop for
      children with SLI that operated at all levels of a hierarchical tripartite model
      of working memory (Baddeley and Hitch 1974). These findings imply that low scores
      on complex working memory tasks alone do not unequivocally imply an independent
      deficit in central executive (domain-general) resources of working memory and
      should therefore be treated cautiously in a clinical context.

PMID- 18821160
TI  - Test-retest stability on the WRAT-3 reading subtest in geriatric cognitive
      evaluations.
AB  - The primary goal of this study was to establish the stability of the Wide Range
      Achievement Test (WRAT-3) Reading score across two annual assessments of aging
      individuals. Participants were classified as controls (n = 200), mild cognitive
      impairment (MCI; n = 137), or possible or probable Alzheimer's disease (AD; n =
      41). Test-retest stability was acceptable to high for all diagnostic groups. The
      descriptive classification (e.g., "average") remained consistent for only 74% of
      participants. Results indicated that WRAT-3 Reading scores are appropriate for
      use with older adults, though the use of categorical descriptors to describe
      premorbid ability based on these scores is not supported.

PMID- 18821162
TI  - The role of intellectual openness in the relationship between hand preference and
      positive schizotypy.
AB  - Recently it has been suggested that the relationship between positive schizotypy
      and mixed handedness is limited to questionnaire measures, and thus reflects some
      aspect of questionnaire-taking behaviour as opposed to some aspect of atypical
      brain organisation. The current study set out to explore this possibility.
      Undergraduate psychology students completed the Magical Ideation Scale, the
      Waterloo Handedness Questionnaire-Revised, a manual dot-filling task, and an
      inventory measuring the personality trait of intellectual openness. On the
      questionnaire measure, magical ideation was related to mixed handedness on
      unskilled but not skilled hand preference; however, this relationship was
      partially mediated by intellectual openness. Magical ideation was not related to
      the behavioural measure of handedness. These findings suggest that responses on
      handedness questionnaires partially reflect personality variables, and such
      effects should be considered in future research on the nature of the relationship
      between handedness and schizotypy.

PMID- 18821163
TI  - The potential of the inventory of learning styles to study students' learning
      patterns in three types of medical curricula.
AB  - BACKGROUND: Introducing innovative curricular designs can be evaluating by
      scrutinizing the learning patterns students use. AIM: Studying the potential of
      Vermunt's Inventory of Learning Styles (ILS) in detecting differences in student
      learning patterns in different medical curricula. METHODS: Cross-sectional
      between-subjects comparison of ILS-scores in third-year medical students in a
      conventional, an integrated contextual and a PBL-curriculum using one-way post
      hoc ANOVA. RESULTS: Response rate was 85%: 197 conventional, 130 integrated
      contextual and 301 PBL students. The results show a differential impact from the
      three curricula. In relation to processing strategies, the students in the
      problem-based curriculum showed less rote learning and rehearsing, greater
      variety in sources of knowledge used and less ability to express study content in
      a personal manner than did the students in the conventional curriculum. The
      students of the integrated contextual curriculum showed more structuring of
      subject matter by integrating different aspects into a whole. In relation to
      regulation strategies, the students in the problem-based curriculum showed
      significantly more self-regulation of learning content and the students in the
      integrated contextual curriculum showed lower levels of regulation. As to
      learning orientations, the students in the problem-based curriculum showed less
      ambivalence and the students of the conventional curriculum were less
      vocationally oriented. CONCLUSION: The study provides empirical support for
      expected effects of traditional and innovative curricula which thus far were not
      well supported by empirical studies.

PMID- 18821164
TI  - Twelve tips for excellent physical examination teaching.
AB  - BACKGROUND: Physical examination (PEx) skills are declining among medical
      trainees, yet many institutions are not teaching these systematically and
      effectively. Many variables contribute to effective teaching: teachers'
      confidence in their clinical skills, ability to demonstrate and assess these
      skills; availability of suitable patients; trainee attitude and fatigue; belief
      that institutions do not value clinical teachers. Finally, the relevance and
      significance of a systematic exam must be demonstrated or the teaching
      degenerates into a 'show-and-tell' exercise. AIMS: This paper describes twelve
      practical teaching tips that can be used to promote high quality PEx teaching in
      5 minutes or 45 minutes. TEACHING TIPS: (1) Diagnostic hypotheses should guide
      reflective exam; (2) Teachers with the best clinical skills should be recruited;
      (3) A longitudinal and systematic curriculum can tailor teaching to multiple
      learner levels (4) Integration of simulation and bedside teaching can maximise
      learning; (5) Bedside detective work and games make learning fun; (6) The 6-step
      approach to teach procedures can be adopted to teach PEx; (7) Clinical teaching
      at the bedside should be increased; (8) Linking basic sciences to clinical
      findings will demonstrate relevance; (9) Since assessment drives learning,
      clinical skills should be systematically assessed; (10) Staff development can
      target improvement of teachers' clinical skills for effective teaching; (11)
      Technology should be used to study utility of clinical signs; (12) Institutions
      should elevate the importance of clinical skills teaching and recognize and
      reward teachers. CONCLUSIONS: PEx is important in patient-physician interactions,
      a valuable contributor to accurate clinical diagnosis and can be taught
      effectively using practical tips. To reverse the trend of deficient clinical
      skills, precision of clinical findings should be studied and exam manoeuvres that
      do not contribute to diagnosis discarded; institutions should value clinical
      skills teaching, appoint and fund core faculty to teach and provide staff
      development to improve teaching skills.

PMID- 18821165
TI  - What is a clinical pearl and what is its role in medical education?
AB  - BACKGROUND: Despite the advent of evidence-based medicine, clinical pearls,
      verbal and published, remain a popular and important part of medical education.
      AIMS: The purpose of this study was to establish a definition of a clinical pearl
      and to determine criteria for an educationally sound clinical pearl. METHODS: The
      authors searched the Medline database for material dealing with clinical pearls,
      examined and discussed the information found, and formulated a consensus opinion
      regarding the definition and criteria. RESULTS: Clinical pearls are best defined
      as small bits of free standing, clinically relevant information based on
      experience or observation. They are part of the vast domain of experience-based
      medicine, and can be helpful in dealing with clinical problems for which
      controlled data do not exist. CONCLUSIONS: While there are no universally
      accepted criteria for preparing or evaluating a clinical pearl, we propose some
      rational guidelines for both.

PMID- 18821166
TI  - Eliminating the memory blocking effect.
AB  - Six experiments investigated the memory blocking effect (MBE) in which exposure
      to orthographically similar words (e.g., BALLOON) impairs one's ability to
      complete a similar fragment (e.g., BAL_ON_, solution is BALCONY). Experiments 1
      and 2 demonstrated that blocking is not observed after a 72-hour delay; however,
      repetition priming was observed after the same delay. Experiments 3 and 4 showed
      that presenting unrelated semantic information during the fragment completion
      test eliminates blocking. Experiment 5 demonstrated that the MBE persists despite
      directed-forgetting instructions, and Experiments 5 and 6 demonstrated that
      activating both the solutions and blocking words for a particular fragment at
      study eliminates blocking. Collectively, the data demonstrate that reading
      orthographically similar primes automatically triggers retrieval of the blocking
      word and an executive control process works to manage this interference. A
      working framework that describes how an executive control mechanism could govern
      memory retrieval in the memory-blocking paradigm is presented to stimulate
      development of more advanced theoretical models that can explain blocking.

PMID- 18821167
TI  - Effects of dividing attention during encoding on perceptual priming of unfamiliar
      visual objects.
AB  - According to the distractor-selection hypothesis (Mulligan, 2003), dividing
      attention during encoding reduces perceptual priming when responses to non
      critical (i.e., distractor) stimuli are selected frequently and simultaneously
      with critical stimulus encoding. Because direct support for this hypothesis comes
      exclusively from studies using familiar word stimuli, the present study tested
      whether the predictions of the distractor-selection hypothesis extend to
      perceptual priming of unfamiliar visual objects using the possible/impossible
      object decision test. Consistent with the distractor-selection hypothesis,
      Experiments 1 and 2 found no reduction in priming when the non-critical stimuli
      were presented infrequently and non-synchronously with the critical target
      stimuli, even though explicit recognition memory was reduced. In Experiment 3,
      non-critical stimuli were presented frequently and simultaneously during encoding
      of critical stimuli; however, no decrement in priming was detected, even when
      encoding time was reduced. These results suggest that priming in the
      possible/impossible object decision test is relatively immune to reductions in
      central attention and that not all aspects of the distractor-selection hypothesis
      generalise to priming of unfamiliar visual objects. Implications for theoretical
      models of object decision priming are discussed.

PMID- 18821168
TI  - Tactile-emotion synesthesia.
AB  - We discuss experiments on two individuals in whom specific textures (e.g., denim,
      wax, sandpaper, silk, etc.) evoked equally distinct emotions (e.g., depression,
      embarrassment, relief, and contentment, respectively). The test/retest
      consistency after 8 months was 100%. A video camera recorded subjects' facial
      expressions and skin conductance responses (SCR) were monitored as they palpated
      different textures. Evaluators' ratings significantly correlated with the valence
      of synesthetes' subjective reports, and SCR was significantly enhanced for
      negative synesthetic emotions. We suggest this effect arises from increased cross
      activation between somatosensory cortex and insula for 'basic' emotions and
      fronto-limbic hyperactivation for more subtle emotions. It may represent an
      enhancement of pre-existing evolutionarily primitive interactions between touch
      and emotions.

PMID- 18821169
TI  - Case report: A prototypical spontaneous 'sensed presence' of a sentient being and
      concomitant electroencephalographic activity in the clinical laboratory.
AB  - The sensed presence of a 'Sentient Being' has been hypothesized to be the
      transient awareness of the right hemispheric equivalent of the left hemispheric
      sense of self. When the clinical context is supportive for the expression of
      anomalous cognition, the experience is reported frequently by patients who
      display complex partial epileptic-like symptoms and signs following a mild closed
      head injury. This article describes a patient with a history of presences
      subsequent to a 'mild' closed head injury who reported strong experiences during
      an electroencephalographic screening within a very quiet and darkened setting at
      the end of a day of neuropsychological assessments. The right-sided presence was
      preceded by the sensation of an 'electric shock' through the right hand and then
      both hands. Whole body 'icy coldness' and then vibrations 'moved' through her
      entire body. The experiences were concomitant with paroxysmal irregular 4-5-Hz
      activity over the temporal lobes. This case illustrates that many sensed
      presences might be similar to 'epileptic auras' for patients who also display
      elevated complex partial epileptic-like experiences following closed head
      injuries and that close attention to typically ignored electroencephalographic
      'transients' may be helpful indicators.

PMID- 18821170
TI  - Differentiated expression of the lactate dehydrogenase subunit M in pleural
      fluids of neoplastic aetiology.
AB  - OBJECTIVE: An anaerobic type of glycolysis exemplified by hyperproduction of the
      lactate dehydrogenase (LDH) subunit M has been detected in lung tumours, while a
      similar pattern has been found in concomitant pleural effusions (PE). The aim of
      this study was to verify the presence of the LDH subunit M in PEs of different
      aetiology and to compare its expression with markers of inflammation. MATERIAL
      AND METHODS: LDH isoenzymes were estimated and the LDH5/LDH1 coefficient was
      calculated in paraneoplastic PEs (n = 99), including subgroups with a different
      tumour ultrastructure, origin and pleural involvement. The expression pattern was
      compared with parainflammatory PEs (n = 21), transudates (n = 16) and with the
      expression of 13 inflammatory markers in PEs. RESULTS: The LDH5/LDH1 coefficient
      was higher in PEs associated with non-small-cell lung cancer (NSCLC) and with
      pleura-invading tumours, and lower in PEs of small-cell lung cancer and tumours
      without a confirmed pleural involvement. The LDH5/LDH1 coefficient positively
      correlated with uPA, IL-8, IL-10, sICAM, sVCAM, MPO and MMP-9. CONCLUSIONS: In
      accordance with inflammatory markers, it appears that the expression of LDH and
      its isoenzymes in PEs reflects the host reaction in pleural space and, in NSCLC,
      may also feature the anaerobic phenotype of cancer cells.

PMID- 18821171
TI  - Prospective, randomized comparison of mechanical and electronic radial endoscopic
      ultrasound systems: assessment of performance parameters and image quality.
AB  - OBJECTIVE: Implementation of electronic image technology in endoscopic
      ultrasonography (EUS) should improve image quality, but systematic data are
      scarce. The purpose of this study was to compare the image quality and
      performance of an electronic and a mechanical radial echoendoscope. MATERIAL AND
      METHODS: Eighty consecutive patients (42 M, mean age 56 years) in a tertiary
      referral center, without gross pathology (advanced tumors excluded), were
      prospectively randomized to EUS with the mechanical or electronic echoendoscope.
      Images from five standardized positions (pancreatobiliary and upper
      gastrointestinal (GI) tract) were taken by two examiners of differing experience.
      Time to acquire images was noted. Penetration depth was also measured. Image
      quality variables (overall quality, contrast, and structure discrimination) were
      assessed blindly on the basis of randomly shuffled images during three
      independent evaluations by the same experienced examiner (mean values were
      taken), using a visual analogue scale (VAS) from 1 (excellent) to 10
      (inadequate). RESULTS: Time needed to achieve visualization of the distal common
      bile duct (CBD) was significantly shorter with the electronic scope (49.7+/-8.6
      versus 97.4+/-8.5 s; p<0.001). Image quality with the electronic scope was rated
      significantly better for all variables assessed, whereas EUS penetration depth
      was similar in both groups. There were no differences in examiner experience.
      CONCLUSIONS: Electronic EUS provided better quality images according to the
      examiner's subjective assessment. An objective advantage was faster
      identification of the distal CBD.

PMID- 18821172
TI  - Pulmonary hypertension in primary biliary cirrhosis: a prospective study in 178
      patients.
AB  - OBJECTIVE. To analyze the incidence, clinical features, and prognosis of patients
      with primary biliary cirrhosis (PBC) complicated by pulmonary hypertension (PH).
      MATERIAL AND METHODS: A total of 178 consecutive PBC patients, who were admitted
      to Peking Union Medical College Hospital from January 2001 to March 2007, were
      included in this prospective study. A structured interview, systemic
      rheumatological examination, laboratory tests (including autoantibodies), and
      Doppler echocardiography were conducted for each patient and compared between
      patients with and without PH. RESULTS: Twenty-one PBC patients (11.8%) had PH.
      Among them, four patients (19.0%) had moderate to severe PH, and one patient died
      of right heart failure instead of liver failure. The incidences of Raynaud's
      phenomenon, interstitial lung disease, Sjogren's syndrome, and portal
      hypertension, the proportion of patients with a positive anti-SSA, the level of
      serum IgA, as well as the Mayo risk score in the PH-PBC patients were
      significantly higher than in the non-PH-PBC group (p = 0.02, 0.001, 0.02, 0.03,
      0.006, 0.04 and 0.02, respectively). CONCLUSIONS: PH, including moderate to
      severe PH, is not a rare complication of PBC. This complication is closely
      associated with portal hypertension and immunological dysregulation and indicates
      a poor prognosis.

PMID- 18821173
TI  - Psychological associations of irritable bowel syndrome besides panic disorder: an
      often overlooked reality.

PMID- 18821174
TI  - Immunotherapy in colorectal cancer.

PMID- 18821175
TI  - Detection of respiratory viruses and Legionella spp. by real-time polymerase
      chain reaction in patients with community acquired pneumonia.
AB  - We conducted a study on throat swabs obtained from a group of hospitalized
      patients with community acquired pneumonia (CAP). Throat swab specimens from 242
      adults admitted to hospital with CAP were tested. In total, 1 or more
      aetiological agents were identified by real-time PCR in 55 (23%) patients. The
      most frequently detected pathogens were coronavirus (17%), parainfluenza virus
      (6%) and influenza virus (4%). Overall, viral pathogens were identified by
      conventional techniques in 7 (2%) patients, and real-time PCR in 50 (21%)
      patients (p<0.0001). The diagnostic yield increased from 137 cases (57% of
      patients using conventional microbiological assays) to 158 cases (65% of patients
      using real-time PCR assays and conventional microbiological assays; p=0.06). A
      significantly higher percentage of mortality was present in patients with a mixed
      bacterial and viral infection. L. pneumophila PCR was positive in only 3 out of
      11 cases (27%) of Legionnaires' disease (LD). This study demonstrates that real
      time PCR can increase the number of microbiological detections of respiratory
      pathogens, mainly as a result of detection of respiratory viruses.

PMID- 18821176
TI  - Burden of viral respiratory disease hospitalizations among children in a
      community of Seoul, Republic of Korea, 1995 - 2005.
AB  - Our objective was to describe respiratory disease hospitalizations among children
      in a community of Seoul, Republic of Korea. Discharge data (January 1995-December
      2005) from Guro Hospital (Seoul, Republic of Korea) were collected from the
      hospital medical records office. Respiratory virus test results (March 2004
      December 2005) and hospitalization charges to the National Health Insurance
      Corporation (January 2002-December 2005) were provided by hospital laboratory and
      administrative departments. Variations in hospitalizations, test results and
      total hospitalization-associated medical charges were described by age, clinical
      complaint, discharge month and length of stay. Over the 11-y period, 4247
      paediatric hospitalizations for lower respiratory disease occurred. Semi-annual
      epidemics were identified in October-December and April-May. Among a subset
      (n=400) of patients, 48% had respiratory syncytial virus, 16% parainfluenza
      virus, 19% influenza viruses and 17% adenovirus infection. On admission, children
      had respiratory problems (53%), fever (39%), or other systemic problems (8%). The
      median charge of a lower respiratory disease hospitalization was highest in
      January ($1334) and lowest in October ($1076). Median hospitalization charges
      were highest among children 8-15 years of age compared with younger children </=2
      years and those 3-7 years of age. Respiratory disease hospitalizations among
      children demonstrated annual variations reflecting patterns of children with
      laboratory-confirmed respiratory viral infections. In the Republic of Korea,
      prospective studies that use standardized laboratory testing for respiratory
      pathogens in children will help to estimate the total burden of viral lower
      respiratory tract disease.

PMID- 18821177
TI  - Occupational therapy, professional development, and ethics.
AB  - The aim of this article is to reflect on and contribute to developing
      occupational therapy as a profession. The author proposes an ethical
      interpretation of health and helping professions in general and occupational
      therapy in particular. According to this ethical interpretation, the essential
      function and mission of classical health and helping professions are defined by
      certain ethical values: the basic elements of a good human life. The author
      argues that the central concepts of occupational therapy, activity and
      participation, can plausibly be understood in this light. However, this seems to
      imply a rather substantial conception of well-being which the author tries to
      spell out. In addition, the basic principles of biomedical ethics are specified
      in the context of occupational therapy according to an ethical interpretation. In
      conclusion, four advantages of the ethical interpretation are highlighted: it
      adds precision and content to ethical principles and guidelines; it contributes
      to building up and preserving a shared professional identity; it puts emphasis on
      a client-centred perspective on professional work; and it provides a constructive
      framework for inter-professional cooperation.

PMID- 18821178
TI  - Prevalence of spondyloarthritis in 504 Chinese patients with HLA-B27-associated
      acute anterior uveitis.
AB  - OBJECTIVES: To estimate the prevalence of spondyloarthritis (SpA) and the
      clinical features of human leucocyte antigen (HLA)-B27-associated acute anterior
      uveitis (HLA-B27 uveitis) in Chinese patients. METHODS: We conducted a
      retrospective cohort study using a structured chart review to record the complete
      ocular history, including the onset of uveitis, month of uveitis attack, specific
      eye involvement, the time of first attack, and rheumatic manifestations from 1987
      to 2004. A total of 504 patients with HLA-B27 uveitis were consequently enrolled
      consecutively from the uveitis clinic of Taipei Veterans General Hospital.
      RESULTS: In total, 1719 attacks of uveitis in 504 patients were recorded. Females
      tended to have a higher frequency of attack than males, and those with a disease
      course of less than 5 years showed more uveitis recurrence. The same eye attacks
      were observed in 156 of 332 patients (47%), more than the expected percentage
      compared with attacks with random-eye occurrence (p < 0.001). A significantly
      higher number of uveitis attacks occurred in winter. SpA-related acute anterior
      uveitis (AAU) was found in 387 patients (76.8%). Ankylosing spondylitis (AS)
      occurred in 214 patients (42.5%), with a significantly higher prevalence in males
      than in females (p < 0.001). Undifferentiated SpA (USpA)-related AAU occurred in
      150 patients (29.8%), with a significantly higher prevalence in females than in
      males (p < 0.001). Patients with SpA had an earlier onset of uveitis (p = 0.01)
      and a greater number (> or = 6) of attacks (p = 0.03). CONCLUSIONS: The
      prevalence of SpA was high in the Chinese population with HLA-B27-associated
      uveitis. The association with SpA indicated an earlier age of uveitis onset and a
      greater likelihood of having a higher number of uveitis attacks.

PMID- 18821179
TI  - Evidence-based research and practice in clinical neuropsychology.
AB  - While a definition for evidence-based clinical neuropsychological practice
      (EBCNP) has yet to emerge, it is likely to integrate the same core features as
      evidence-based medicine; namely, best research evidence, clinical expertise, and
      individual patient needs. Given the nascent stage of EBCNP, suggestions are made
      to advance evidence-based approaches in both research and practice. The common
      elements are: recognition that clinical outcomes are recorded at the level of the
      individual; and to be useful, outcomes research must be presented in a way that
      can be directly applied on a case-by-case basis. Tracking the outcomes of our
      clinical services in an evidence-based manner that is publicly verifiable will
      demonstrate the value of neuropsychological services to our patients, our
      referral sources, and ultimately to payers.

PMID- 18821180
TI  - Cognitive declines one year after unilateral deep brain stimulation surgery in
      Parkinson's disease: a controlled study using reliable change.
AB  - Conflicting research suggests that deep brain stimulation surgery, an effective
      treatment for medication-refractory Parkinson's disease (PD), may lead to
      selective cognitive declines. We compared cognitive performance of 22 PD patients
      who underwent unilateral DBS to the GPi or STN to that of 19 PD controls at
      baseline and 12 months. We hypothesized that compared to PD controls, DBS
      patients would decline on tasks involving dorsolateral prefrontal cortex
      circuitry (letter fluency, semantic fluency, and Digit Span Backward) but not on
      other tasks (Vocabulary, Boston Naming Test), and that a greater proportion of
      DBS patients would fall below Reliable Change Indexes (RCIs). Compared to
      controls, DBS patients declined only on the fluency tasks. Analyses classified
      50% of DBS patients as decliners, compared to 11% of controls. Decliners
      experienced less motor improvement than non-decliners. The present study adds to
      the literature through its hypothesis-driven method of task selection, inclusion
      of a disease control group, longer-term follow-up and use of Reliable Change. Our
      findings provide evidence that unilateral DBS surgery is associated with verbal
      fluency declines and indicate that while these changes may not be systematically
      related to age, cognitive or depression status at baseline, semantic fluency
      declines may be more common after left-sided surgery. Finally, use of Reliable
      Change highlights the impact of individual variability and indicates that fluency
      declines likely reflect significant changes in a subset of patients who
      demonstrate a poorer surgical outcome overall.

PMID- 18821181
TI  - Longitudinal changes in memory and executive functioning are associated with
      longitudinal change in instrumental activities of daily living in older adults.
AB  - Impaired everyday function is a diagnostic criterion for dementia, and a
      determinant of healthcare utilization and caregiver burden. Although many
      previous studies have demonstrated a cross-sectional relationship between
      cognition (particularly executive functions and memory) and everyday function in
      older adults, very little is known about longitudinal relationships between these
      domains. This study examined the association between longitudinal change in
      episodic memory (MEM) and executive functioning (EXEC) and change in everyday
      function. Participants were a cognitively heterogeneous group of 100 elderly
      persons including those with normal cognition, as well as those with mild
      cognitive impairment and dementia. They were followed for an average of 5 years.
      Random effects modeling showed that change in both MEM and EXEC were
      independently associated with rate of change in informant-rated instrumental
      activities of daily living (IADLs), even after controlling for age, education,
      and gender. Findings indicate that declines in MEM and EXEC over time make unique
      and independent contributions to declines in older adults' ability to function in
      daily life.

PMID- 18821182
TI  - The COPD Italian Lung Information Needs Questionnaire (LINQ): development,
      preliminary validation, and findings.
AB  - Chronic obstructive pulmonary disease (COPD) patients have poor knowledge about
      the disease. Until now, it has not been possible to check the information needs
      of these patients. The Lung Information Needs Questionnaire (LINQ), however,
      could fill this particular need. The aims of this study were to identify patient
      perceptions about COPD, and what information patients need, and to verify whether
      the questionnaire is comprehensible. Data demonstrate that LINQ is easily
      understood: 82% answered all questions with "I have properly understood the
      question". LINQ is quick to apply (approx. 6 min to complete). Sixty-seven per
      cent of patients had incorrect knowledge about their prognosis. Thirty-six per
      cent did not know when to call an ambulance. Eight per cent of smokers said that
      no one had ever told them to stop smoking. Compliance with therapy results was
      not sufficient. Patients had poor knowledge of the causes of COPD, and they knew
      little about the whys and wherefores of COPD treatment. LINQ represents a valid
      means of investigating patients afflicted with COPD and managing pathology
      control by the doctor and by the patient. LINQ represents a fundamental means of
      investigating otherwise-unknown COPD issues.

PMID- 18821183
TI  - Treatment of bipolar disorder: new perspectives.
AB  - Treatment of bipolar disorder (BD) has traditionally focused on alleviation of
      acute symptoms and prevention of future recurrences. Current treatment guide
      lines advocate more or less similar treatment algorithms for all patients. Such
      approach largely ignores the clinical, genetic, and pathophysiological
      heterogeneity of BD, which makes certain patients more (or less) likely to
      respond to specific treatments. Variables such as family history, comorbidity,
      course of illness, quality and duration of previous remissions, physical and
      medical comorbidity, and side-effects may help in selecting the most effective
      treatment for an individual patient, yet their value is not recognized by current
      algorithms. As well, polymorphisms of specific genes may prove useful in
      predicting treatment outcome and/or understanding the pharmacological mechanisms
      of mood stabilization. Novel molecular targets have recently emerged from studies
      of mechanisms of action of available mood stabilizers. They include inhibitors of
      protein kinase C, inhibitors of glycogen synthase kinase, or medications
      modulating glutamatergic neurotransmission. As well, treatment targets are moving
      beyond acute symptoms and prevention of mood episodes. Cognitive deficits,
      persistence of residual symptoms, and increased mortality of BD are recognized as
      important for outcome of BD, yet are not always adequately addressed by
      traditional treatments.

PMID- 18821184
TI  - Transmission of tuberculosis between men and pet birds: a case report.
AB  - The present report describes a case of Mycobacterium tuberculosis infection in an
      African Grey parrot (Psittacus erithacus erithacus) kept as a pet bird. Diagnosis
      was confirmed by microbiologic and pathologic results, and indicated a human
      avian transmission. Clinical signs included sublingual nodules resulting in
      anorexia and signs of osteolysis in the long bones. Proliferation consisted of
      several nodules with small greenish-caseous foci in cross-section and revealed a
      severe granulomatous inflammation without intralesional acid-fast rods. M.
      tuberculosis was cultured from a pooled sample of sublingual and liver nodules,
      and was confirmed via polymerase chain reaction. Transmission between men and
      parrot was proved by spoligotyping pattern analysis. The absence of facial skin
      lesions and acid-fast rods within the tubercles is contrary to previous
      publications of tuberculosis in birds. This disease in a common pet bird species
      is of zoonotic importance, and those parrots with close contact to owners
      suffering from tuberculosis may serve as a potential reservoir for human
      infection.

PMID- 18821185
TI  - The impact of occult renal failure on the cardiovascular risk stratification in
      an elderly population: the PREV-ICTUS study.
AB  - BACKGROUND AND OBJECTIVES: To analyze the impact of occult renal failure (ORF) in
      the individual risk stratification and on the blood pressures (BP) and low
      density lipoprotein (LDL) goals in an aged population, according to the ESH/ESC
      Hypertension Guidelines. METHODS: A cross-sectional, population-based study on
      individuals aged 60 years or more carried out in Primary Care Centers of Spain.
      Kidney function was estimated from calculated creatinine clearance (eGFR),
      Cockroft and Gault formula. Ten-year cardiovascular risk was estimated through
      the ESH/ESC table including or not including the eGFR. Estimates of the
      modification in BP and LDL-cholesterol (cLDL) goals were calculated. RESULTS: In
      6419 subjects, 4242 subjects (66%) had normal renal function, 1971 (31%) had ORF
      (normal creatinine and low eGFR) and 206 (3%) had insufficient renal function
      (high creatinine and all of them low eGFR). Inclusion of ORF as target organ
      damage resulted in an increase in the estimated risk in 10.8% of the total
      sample, increasing the percentage of high-risk subjects. In the latter case, new
      BP and cLDL goals (<130/80 mmHg and <100 mg/dl) should be needed in 475 (7.4%)
      and 413 (6.4%) additional subjects, respectively. CONCLUSION: Inclusion of the
      ORF resulted in a significant increase in the percentage of subjects with
      estimated high cardiovascular risk.

PMID- 18821186
TI  - Climacteric, physically active women ingesting their routine diet oxidize more
      carbohydrates than lipids.
AB  - OBJECTIVE: To investigate the influence of a routine Brazilian diet on the rate
      of oxidation of energy substrates in climacteric, obese women, who came to the
      outpatient clinic of the Hospital of the School of Medicine of Ribeirao Preto
      (HCFMRP-USP). METHODS: Subjects were recruited from outpatients at the
      Climacteric Clinic of the HCFMRP-USP, who were aged between 39 and 65 years and
      who voluntarily agreed to participate in this study. They were submitted to
      anthropometric measurements and indirect calorimetry for resting energy
      expenditure and substrate oxidation rate determination. RESULTS: The carbohydrate
      oxidation in the group of climacteric, obese women showed a significant positive
      correlation between energy consumption at rest and ingestion of carbohydrates (in
      grams); the subjects' rate of lipid intake showed a significant negative
      correlation with their body mass index, waist circumference, and daily total
      caloric intake. CONCLUSION: Carbohydrate intake and carbohydrate oxidation rate
      may contribute to weight gain in climacteric women.

PMID- 18821189
TI  - Stresses in peripheral arteries following stent placement: a finite element
      analysis.
AB  - The success of stents to restore blood flow in atherosclerotic peripheral
      arteries is low relative to coronary arteries. It has been shown that joint
      flexion induces a mechanical environment that makes stent placement in these
      arteries highly incompatible, and damage and destruction of stents has been
      recorded. However, the effect of this environment on the stresses in the arteries
      is unknown. It is hypothesised that the stresses induced in arteries as a result
      of this mechanical environment could be sufficient to explain the relatively low
      success rates. To investigate this hypothesis, a finite element model of the
      stent-artery interaction was developed. Following stent expansion, bending was
      simulated by applying a displacement boundary condition to the artery. It is
      found that high stresses occur at the proximal/distal ends of the stent. As high
      stress and vascular injury are hypothesised to cause restenosis, the results
      presented here suggest that the mechanical environment of peripheral arteries
      could be the predominant cause of high restenosis rates.

PMID- 18821190
TI  - Global/local head models to analyse cerebral blood vessel rupture leading to ASDH
      and SAH.
AB  - Blunt and rotational head impacts due to vehicular collisions, falls and contact
      sports cause relative motion between the brain and skull. This increases the
      normal and shear stresses in the (skull/brain) interface region consisting of
      cerebrospinal fluid (CSF) and subarachnoid space (SAS) trabeculae. The relative
      motion between the brain and skull can explain many types of traumatic brain
      injuries (TBI) including acute subdural hematomas (ASDH) and subarachnoid
      hemorrhage (SAH) which is caused by the rupture of bridging veins that transverse
      from the deep brain tissue to the superficial meningeal coverings. The
      complicated geometry of the SAS trabeculae makes it impossible to model all the
      details of the region. Investigators have compromised this layer with solid
      elements, which may lead to inaccurate results. In this paper, the failure of the
      cerebral blood vessels due to the head impacts have been investigated. This is
      accomplished through a global/local modelling approach. Two global models, namely
      a global solid model (GSM) of the skull/brain and a global fluid model (GFM) of
      the SAS/CSF, were constructed and were validated. The global models were
      subjected to two sets of impact loads (head injury criterion, HIC = 740 and
      1044). The relative displacements between the brain and skull were determined
      from GSM. The CSF equivalent fluid pressure due to the impact loads were
      determined by the GFM. To locally study the mechanism of the injury, the relative
      displacement between the brain and skull along with the equivalent fluid pressure
      were implemented into a new local solid model (LSM). The strains of the cerebral
      blood vessels were determined from LSM. These values were compared with their
      relevant experimental ultimate strain values. The results showed an agreement
      with the experimental values indicating that the second impact (HIC = 1044) was
      strong enough to lead to severe injury. The global/local approach provides a
      reliable tool to study the cerebral blood vessel ruptures leading to ASDH and/or
      SAH.

PMID- 18821191
TI  - From disablement to enablement: conceptual models of disability in the 20th
      century.
AB  - PURPOSE: The aim of this work is to provide a general view of the conceptual
      elaborations on disablement in the 20th century and to discuss the role of these
      different contributions in developing the current concepts of disablement.
      METHOD: A review of the literature on conceptual models of disablement in the
      past century has been performed. RESULTS: The 20th century has witnessed
      important theoretical considerations on health, diseases and their consequences.
      These considerations have generated various conceptual models, some of which
      share the same focus and point of arrival, the so-called 'Disablement Process'.
      Among the models that were developed, two stand out, which were drafted and
      disseminated under the aegis of the World Health Organization, namely the
      International Classification of Impairments, Disabilities and Handicaps (ICIDH)
      and the International Classification of Functioning, Disability and Health (ICF),
      but these are just one part of the conceptual elaboration in the field. Further
      conceptualization was produced in health and social settings by specialists, self
      advocacy associations and activist groups. CONCLUSIONS: The current ICF model of
      the World Health Organization has been translated and recognized in 191
      countries; it also incorporates the contribution of self-advocacy associations
      and it is now recognized by most of them. This model has enjoyed higher
      visibility than other conceptual models, though its level of development was not
      higher or more original. To our opinion the ICF is not very clear on the
      essential choice of the model, i.e., to see disablement as a dynamic process that
      happens when personal limits collide with socio-environmental needs, rather than
      as a personal feature. This choice is instead clearer in other models, like
      Nagi's 1991, the Institute of Medicine (IOM) model by Brandt and Pope, where the
      identification of three dimensions (the individual, the environment and the
      individual-environment interaction) clarifies the role played by all three
      dimensions within the process of disablement and introduces major hints for
      further considerations on how to create virtuous processes of enablement.

PMID- 18821192
TI  - Unmet needs and health care utilization in young adults with cerebral palsy.
AB  - PURPOSE: To gain insight into the unmet needs and utilization of health care of
      young adults with cerebral palsy (CP) and to explore relations between unmet
      needs, health care utilization and subject characteristics. METHOD: A cross
      sectional study was performed in 29 young adults with CP without severe learning
      disabilities (IQ > 70). Subject characteristics such as age, gender, limb
      distribution, level of gross motor functioning, level of education and perceived
      participation and autonomy were measured. Outcome measures were the Southampton
      Needs Assessment Questionnaire, Impact on Participation and Autonomy and a
      questionnaire on health care utilization. RESULTS: Young adults with CP reported
      unmet needs mostly on information (79%), mobility (66%) and health care (66%).
      About half of the participants visited a rehabilitation physician (52%) or a
      physical therapist (55%) in the past year. Participants with lower levels of
      gross motor functioning were found to have more unmet needs and visited various
      health care professionals more often than young adults with higher levels of
      gross motor functioning. However, participants with higher levels of gross motor
      functioning still reported several unmet needs. CONCLUSIONS: Although young
      adults with CP frequently receive treatment from health care professionals, they
      indicate unmet needs with respect to several areas such as information on
      diagnosis, functional mobility and formal health care. In the treatment of young
      adults with CP, attention should be paid to these aspects.

PMID- 18821193
TI  - Women's experiences of increasing subjective well-being in CFS/ME through leisure
      based arts and crafts activities: a qualitative study.
AB  - PURPOSE: To understand the meanings of art-making among a group of women living
      with the occupational constraints and stigma of CFS/ME. The study explored their
      initial motives for art-making, and then examined how art-making had subsequently
      influenced their subjective well-being. METHOD: Ten women with CFS/ME were
      interviewed; three provided lengthy written accounts to the interview questions.
      FINDINGS: Illness had resulted in devastating occupational and role loss.
      Participants took many years to make positive lifestyle changes. Art-making was
      typically discovered once participants had accepted the long-term nature of
      CFS/ME, accommodated to illness, and reprioritized occupations. Several factors
      then attracted participants specifically to art-making. It was perceived as
      manageable within the constraints of ill-health. Participants also tended to be
      familiar with craft skills; had family members interested in arts and crafts, and
      some desired a means to express grief and loss. Once established as a leisure
      activity, art-making increased subjective well-being mainly through providing
      increased satisfaction in daily life, positive self-image, hope, and contact with
      the outside world. Participants recommended provision of
      occupational/recreational counselling earlier in the illness trajectory.
      CONCLUSIONS: Creative art-making occurred as part of a broader acceptance and
      adjustment process to CFS/ME, and allowed some psychological escape from a
      circumscribed lifeworld.

PMID- 18821194
TI  - The benefits of theory for clinical practice: cognitive treatment for chronic low
      back pain patients as an illustrative example.
AB  - PURPOSE: To demonstrate, with the help of an example of cognitive treatment for
      patients with chronic low back pain, how a systematic description of the content
      and theoretical underpinnings of treatment can help to improve clinical practice.
      METHODS: A conceptual analysis, two types of theories, and a programme-theory
      framework were instrumental in systematically specifying the content of the
      treatment and the underlying assumptions. RESULTS: A detailed description of the
      cognitive treatment, including: (i) The intended outcomes; (ii) the related
      treatment components; (iii) the therapeutic process that is expected to mediate
      between outcomes and components, (iv) the conditions for optimal application; and
      (v) the guiding principles. CONCLUSIONS: The systematic description of the
      treatment revealed important issues for clinical practice, such as the patient
      and therapist characteristics that are needed for optimal provision of cognitive
      treatment. The discussions on the role of theory in rehabilitation practice are
      taken one step further in this clinical commentary: instead of simply describing
      the problems, we also demonstrated a means to tackle them.

PMID- 18821195
TI  - Tissues distribution of R-(-)- and S-(+)-m-nisoldipine after single enantiomer
      administration in rats.
AB  - Rapid, sensitive, and selective high-performance liquid chromatography methods
      were developed and validated for determination of m-nisoldipine enantiomers in
      rat tissues. All of the samples were prepared based on a simple and efficient
      liquid-liquid extraction method. After validating that no racemation occurred by
      ULTRON ES-OVM (Japan), m-nisoldipine enantiomers were determined, respectively,
      on a reverse-phase C(18) column (5 microm, 250 x 4.6 mm). This method was applied
      to study tissue distribution of m-nisoldipine enantiomers in rats after a single
      administration of m-nisoldipine enantiomers. By the two-sample t test, there were
      basically no significant differences between the two enantiomers in each tissue (
      p > .05), which indicates that they may have the same potency in rats. In small
      intestine, lung, liver, and spleen, the concentrations of R-(-)- and S-(+)-m
      nisoldipine were high at 30 and 150 min than that at 90 min, which showed that m
      nisoldipine enantiomers may have the phenomenon of hepatoenteral circulation. A
      small quantity of the prototype of R-(-)- and S-(+)-m-nisoldipine in brain showed
      that they can cross the blood-brain barrier to arrive at the brain tissue. The
      high quantity of distribution in lung and brain implied that the lipophilicity of
      the drug was powerful.

PMID- 18821196
TI  - Influence of urea, isopropanol, and propylene glycol on rutin in vitro release
      from cosmetic semisolid systems estimated by factorial design.
AB  - Rutin, one of the major flavonoids found in an assortment of plants, was reported
      to act as a sun protection factor booster with high anti-UVA defense,
      antioxidant, antiaging, and anticellulite, by improvement of the cutaneous
      microcirculation. This research work aimed at evaluating the rutin in vitro
      release from semisolid systems, in vertical diffusion cells, containing urea,
      isopropanol and propylene glycol, associated or not, according to the factorial
      design with two levels with center point. Urea (alone and in association with
      isopropanol and propylene glycol) and isopropanol (alone and in association with
      propylene glycol) influenced significant and negatively rutin liberation in
      diverse parameters: flux (microg/cm(2).h); apparent permeability coefficient
      (cm/h); rutin amount released (microg/cm(2)); and liberation enhancement factor.
      In accordance with the results, the presence of propylene glycol 5.0% (wt/wt)
      presented statistically favorable to promote rutin release from this semisolid
      system with flux = 105.12 +/- 8.59 microg/cm(2).h; apparent permeability
      coefficient = 7.01 +/- 0.572 cm/h; rutin amount released = 648.80 +/- 53.01
      microg/cm(2); and liberation enhancement factor = 1.21 +/- 0.07.

PMID- 18821198
TI  - Blood-brain barrier permeability and nerve cell damage in rat brain 14 and 28
      days after exposure to microwaves from GSM mobile phones.
AB  - We investigated the effects of global system for mobile communication (GSM)
      microwave exposure on the permeability of the blood-brain barrier and signs of
      neuronal damage in rats using a real GSM programmable mobile phone in the 900 MHz
      band. Ninety-six non-anaesthetized rats were either exposed to microwaves or sham
      exposed in TEM-cells for 2 h at specific absorption rates of average whole-body
      Specific Absorption Rates (SAR) of 0.12, 1.2, 12, or 120 mW/kg. The rats were
      sacrificed after a recovery time of either 14 or 28 d, following exposure and the
      extravazation of albumin, its uptake into neurons, and occurrence of damaged
      neurons was assessed. Albumin extravazation and also its uptake into neurons was
      seen to be enhanced after 14 d (Kruskal Wallis test: p = 0.02 and 0.002,
      respectively), but not after a 28 d recovery period. The occurrence of dark
      neurons in the rat brains, on the other hand, was enhanced later, after 28 d (p =
      0.02). Furthermore, in the 28-d brain samples, neuronal albumin uptake was
      significantly correlated to occurrence of damaged neurons (Spearman r = 0.41; p <
      0.01).

PMID- 18821199
TI  - Calcium ion cyclotron resonance (ICR) transfers information to living systems:
      effects on human epithelial cell differentiation.
AB  - The specific aim of the present work concerns the effectiveness of low-frequency
      electromagnetic fields treatment to modify biochemical properties of human
      keratinocytes (HaCaT). Cells exposed to a 7 Hz electromagnetic field, tuned to
      calcium ion cyclotron resonance (ICR), showed modifications in the cytoskeleton.
      These modifications were related to different actin distributions as revealed by
      phalloidin fluorescence analysis. Indirect immunofluorescence with fluorescent
      antibodies against involucrin and beta catenin, both differentiation and adhesion
      markers, revealed an increase in involucrin and beta-catenin expression,
      indicating that exposure to electromagnetic field carries keratinocytes to an
      upper differentiation level. This study confirms our previous observation and
      supports the hypothesis that a 7 Hz calcium ICR electromagnetic field may modify
      cell biochemistry and interfere in the differentiation and cellular adhesion of
      normal keratinocytes, suggesting the possibility to use ICR electromagnetic
      therapy for the treatment of undifferentiated diseases.

PMID- 18821200
TI  - Effects of extremely low-frequency magnetic fields on L-glutamic acid aqueous
      solutions at 20, 40, and 60 microT static magnetic fields.
AB  - Current peaks have been observed and measured in electrolytic ionic current of L
      glutamic acid aqueous solutions at room temperature, in static magnetic fields of
      20, 40, and 60 muT flux densities, with a superimposed extremely low-frequency,
      (1/10) Hz, alternating magnetic field flux density of 40 nT. The distributions of
      the peaks have mean values centered at the cyclotron resonance frequency of the
      singly charged L-glutamic acid ion molecular mass in the corresponding static
      field. Amplitudes and widths of the peaks are compared and analyzed to extract
      their correlation. The results can be considered a contribution to the
      understanding of the experimental phenomenology in low-frequency electromagnetic
      fields on ionic currents of L-glutamic amino acid aqueous solutions. The results
      can be of interest in the studies on the interaction of the electromagnetic
      fields with some structural neurotransmitters in cellular medium.

PMID- 18821201
TI  - Threshold of pain in chronic magnetic field- (50 Hz, 17.9 microT) exposed rats:
      effect of sucrose ingestion.
AB  - Both magnetic field (MF) exposure and sucrose ingestion produce opioid mediated
      analgesia, independently. This article addresses the query whether or not sucrose
      ingestion potentiates the analgesia of MF exposure. The pain threshold, as
      reflected by withdrawal of tail (thresholds of tail flick, TF), vocalization
      during stimulus (VD), and vocalization after stimulus (VA) were determined in 7
      sessions at 0, 5, 10, 15, 30, 45, and 60 min, respectively (control rats). After
      an interval of 24 h the rats were provided with sucrose solution and were allowed
      to ingest it for 10 min. The pain thresholds were determined (Control sucrose-fed
      rats). The rats then received exposure to magnetic field (50 Hz, 17.9 microT) for
      7 d (8 h/d) (MF-exposed rats) and the effect of sucrose ingestion was repeated
      (MF-Sucrose-fed rats). The basal threshold of pain did not vary in between the
      control and MF-exposed rats. Pain threshold during sessions II-VII did not vary
      in control rats but it increased in MF rats. Moreover, the pain thresholds were
      elevated in MF rats as compared to control rats. Sucrose-ingestion elevated the
      threshold of TF in controls but not in MF-exposed rats; while the thresholds of
      VA and VD were elevated more in control than MF rats. The results suggest that
      the MF exposure (50 Hz, 17.9 microT, 8 h/d) for 7 d did not affect the basal
      thresholds of pain, increased stress induced analgesia, and attenuated the
      sucrose ingestion-induced analgesia.

PMID- 18821202
TI  - Effect of chronic intermittent exposure to AM radiofrequency field on responses
      to various types of noxious stimuli in growing rats.
AB  - There are several reports of altered pain sensation after exposure (from a few
      minutes to hours in single or repeated doses for 2-3 weeks) to electromagnetic
      fields (EMF) in adults. The commonly utilized noxious stimulus is radiant heat.
      The nociceptive responses are known to be influenced by characteristics of
      stimulus, organism, and environment. We studied the pattern of nociceptive
      responses to various noxious stimuli in growing rats exposed to radiofrequency
      field (73.5 MHz amplitude modulated, 16 Hz power density 1.33 mw/cm(2), SAR = 0.4
      w/kg) for 45 d (2 h/d). Threshold current for stimulation of nociceptive
      afferents to mediate motor response of tail (TF), vocalization during stimulus
      (VD), and vocalization after discharge (VA); the withdrawal latency of tail (TFL)
      and hind paw (HPL) to thermal noxious stimulus and tonic pain responses were
      recorded in every rat. The TFL was not affected, HPL was decreased (p < 0.01),
      and the thresholds of TF and VD were not affected, while, that of VA was
      significantly decreased. The tonic pain rating was decreased (p < 0.01). A
      decrease in the threshold of VA (p < 0.01) is indicative of an increase in the
      emotional component of the response to the phasic pain, whereas a decrease in the
      pain rating indicates analgesia in response to the tonic pain. The results of our
      study suggest that chronic (45 d), intermittent (2 h/d) amplitude modulated RF
      field exposure to the peripubertal rat increases the emotional component of
      phasic pain over a basal eaualgesic state, while late response to tonic pain is
      decreased. The data suggest that amplitude modulated RF field differentially
      affects the mechanisms involved in the processing of various noxious stimuli.

PMID- 18821203
TI  - Changes of leukocyte adherence ability under the influence of magnetic field in
      the course of a treatment of patients with laryngeal and pharyngeal carcinoma.
AB  - The authors were monitoring adherence ability of T lymphocytes in vitro in
      patients with laryngeal and pharyngeal carcinoma at the presence of tumor
      specific and viral LDH antigen. The results were assessed and expressed in
      percent of non adherent T lymphocytes (NAL). First, NAL in patients before
      initiating the treatment was compared with NAL control group (voluntary blood
      donors). The ability of the adherence in T lymphocytes in the control group is
      statistically significantly higher. Further on, NAL in the course of a successful
      oncological treatment was monitored at the interval of 6 months following the
      treatment, and further on at yearly intervals. NAL level drops statistically
      significantly within 6 months and then hold on at levels with no statistical
      difference unlike the control group, however, the ability of T lymphocyte in
      patients to adhere remains statistically significantly lower. Statistically
      significantly higher levels of NAL are at the presence of LDH viral antigen.
      Further on, the authors were following the influence of magnetic sinusoidal field
      of power frequency (50 Hz) of a low induction (0.5, 0.1, and 0.05 mT) on NAL. NAL
      values under the influence of an experimental magnetic field before initiating
      the treatment as well as in the course of a successful oncological treatment are
      statistically significantly lower. It means that magnetic filed increases the
      adherence ability of T lymphocytes in patients with laryngeal and pharyngeal
      cancer in vitro.

PMID- 18821204
TI  - No effect of 50 Hz 2.45 mT magnetic field on the potency of cisplatin, mitomycin
      C, and methotrexate in S. cerevisiae.
AB  - Drug resistance is an obstacle for chemotherapy success. Because of this, this
      work aims to improve the cell killing effect of antineoplastic drugs by magnetic
      field (MF) co-exposure. S. cerevisiae cells were exposed to 2.45 mT, sinusoidal
      50 Hz MF, during 48 h, and the drugs cisplatin (cisPt), mitomycin C (MMC), or
      methotrexate (MTX); 100 and 1,000 microg/ml. Survival was assayed by the drop
      test. The results showed that MF exposures do not induce alterations in the
      potency of cisPt, MMC, and MTX on these cells in relation to untreated controls.
      In addition, a strong correlation between temperature and potency of cisPt was
      found, which contribute to the establishment of the importance of an exhaustive
      control of temperature in experiments carried out with temperature sensitive
      antineoplastic agents in co-exposure with MF; avoiding differences between MF
      exposed samples and unexposed controls and contributing to the performance of
      experiments under well-defined and controlled conditions.

PMID- 18821205
TI  - Effects of extremely low-frequency-pulsed electromagnetic field on different
      derived osteoblast-like cells.
AB  - The aim of this study is to investigate the effects of extremely low-frequency
      pulsed electromagnetic field (PEMF) on osteoblast-like cells. PEMF with a
      magnetic flux density of 1.55 mT at 48 Hz was employed to stimulate the MC3T3-E1
      cell and the primary osteoblast cell derived from 2-day-old Sprague Dawley (SD)
      rat calvaria for different time. MTS method was applied to analyze cell
      proliferation and flow cytometry to detect cell cycle. The intracellular alkaline
      phosphatase (ALP) activity was measured by colorimetry. Our results demonstrated
      that PEMF of 1.55 mT at 48 Hz did not affect cell number of MC3T3-E1 cell,
      whereas the cell percentage of S and G(2)M phase decreased significantly.
      Although the cell number of the primary osteoblast cell did not alter by MTS
      assay after being exposed to PEMF for 24 h continuously, the cell percentage of S
      and G(2)M phase increased significantly. When culture time extended to 48 h, the
      cell number increased greatly and the cell percentage of S and G(2)M phase
      decreased significantly despite of the exposure type. After the primary
      osteoblast cell was exposed to PEMF for 24 h continuously, the ALP activity
      decreased significantly, whereas it increased significantly when being exposed to
      PEMF for 48 h continuously. From the results we concluded that PEMF of 1.55 mT at
      48 Hz did not affect proliferation and differentiation of MC3T3-E1 cell, but it
      promoted proliferation, inhibited differentiation at proliferation stage, and
      promoted differentiation at differentiation stage of primary osteoblast cells.

PMID- 18821206
TI  - Microwave early detection of breast cancers using a virtual-focus scanning
      method.
AB  - In this work, we apply a virtual-focus scanning method to detect a tumor inside a
      simplified two-dimensional breast model via the finite difference time domain
      method. For the purpose of simplification, we construct a microwave detection
      system with an N-element infinitesimal dipole array, and excite the central
      element of the array while letting all elements receive the time-shifted
      scattered fields in order to filter out unwanted signals. With the application of
      the two-step, virtual-focus scanning method, our computerized prototype system
      has accurately detected randomly generated tumors in all cases investigated,
      including small tumors in early stages of development.

PMID- 18821208
TI  - "Honoring a living legend, Phyllis Noerager Stern, DNS, RN, FAAN".

PMID- 18821209
TI  - Aging women's journey toward wholeness: new visions and directions.
AB  - Through a postmodern/feminist exploration of postmenopausal women's narratives,
      set against a backdrop of a discourse analysis of pivotal biomedical texts, we
      revealed women's menopausal and postmenopausal aging life-cycle journey as a
      dynamic, positive, empowering women's process. Based on my analysis of themes in
      women's narratives I argue that the phenomenon of menopause is limited by a
      reductionist model and that a wholisitic model is more appropriate for women as
      they negotiate this significant aging life-cycle process to postmenopausal
      status. Finally, directions for supporting women to develop a wholistic approach
      to positive adult development, and how the aging woman can be given status, are
      suggested.

PMID- 18821210
TI  - Compressing "the sandwiched": an examination of reductionist health policies on
      women in Canada.
AB  - Worldwide, policymakers are critically examining the escalating costs of health
      care. One proposed solution has been to move away from a centralized "general
      hospital"-type of treatment in favor of a family-based model emphasizing health
      as well as treatment. While I agree that such approaches constitute an innovative
      outlook on health care, I draw on a social ecological approach in order to
      attract attention to and lay out the argument for future research examining the
      unacknowledged and unstudied impact that such proposed policies will have on
      women. Undoubtedly, it is they who will bear the brunt of the proposed health
      related responsibilities offloaded by governments. I examine the implications of
      such proposed policies on Canadians, particularly Canadian women, although the
      Canadian system is but an exemplar of the changing dynamics of caregiving in a
      broader world situation.

PMID- 18821211
TI  - Stability and change in health-related behaviors of midlife Swedish women.
AB  - We investigated the dimensions and stability in health-related behaviors (HRBs)
      among midlife Swedish women, and the factors that predicted change in those
      behaviors. At age 43, 569 women from a representative longitudinal sample
      completed questionnaires about lifestyle (diet, exercise, smoking, alcohol) and
      participated in medical screening. Four years later we mailed a follow-up
      questionnaire. HRBs clustered in two dimensions: healthy eating and addictions.
      There was a high degree of stability in HRBs; all women slightly increased their
      HRBs over time. After controlling for previous HRBs, we found that education,
      marital status, and having children at home were significant predictors of HRBs 4
      years later.

PMID- 18821212
TI  - "You really do something useful with kids": mothering and experienced health and
      illness in a group of elderly Swedish women.
AB  - This article is based on in-dept interviews with 20 elderly Swedish women, and
      deals with mother's child-caring work and related health and illness. Mothering
      included invisible work as well as physically heavy tasks, both aspects often
      neglected in research. The attitude of the children's father had a great impact
      on the work. Feelings of success or failure at bringing up their children
      affected the women's experience of health/ill health throughout their lives.
      Their health as elderly women depended on the health and happiness of their, now
      adult, children.

PMID- 18821214
TI  - HLA-class II alleles in Egyptian patients with hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is linked to environmental, dietary, and life
      style factors. Its incidence and distribution vary widely among ethnic groups,
      sex, and geographic regions. HBV and HCV Infection, liver cirrhosis, male gender,
      and old age are important risk factors of HCC. Variability in outcome following
      exposure, and the clustering of HCC within families raise the possibility that
      genetic factors are also involved in susceptibility to HCC. The Major
      Histocompatibility Complex (MHC) plays a key role in anti-virus and tumor
      defense. HLA polymorphism is implicated in conferring genetic susceptibility to a
      large number of immune-mediated diseases, including some cancers. The association
      between HLA class II antigen and HCC in different ethnic populations that has
      been reported is controversial. Therefore, the aim of this work was to study the
      association between HLA class II-DRB1 and DQB1 polymorphism and HCC in Egyptian
      patients and to investigate their role as risk factors for the development of
      HCC. METHODS: HLA-class II (DRB1 and DQB1) typing was done by SSP for 100
      subjects; 50 patients suffering from HCC (45 males and 5 females) with age range
      40-64 years (51.16 years (y) +/- 6.16); and 50 normal healthy control subjects.
      RESULTS: 1. A significantly increased frequency of DRB1*04, and DQB1 *02 in HCC
      patients versus control group (p = 0.016, and 0.032, respectively) was found; 2.
      A significantly decreased frequency of DQB1*06 (p = 0.032) was found; 3. A
      significantly increased frequency of DRB1*07 (odds ratio (OR) = 4.929) was found;
      and 4. A significantly decreased frequency of DRB1*15 (OR = 0.316) was seen. In
      conclusion, while some alleles are significantly associated with HCC (DRB1*04,
      DQB1*02) and others are not associated (DQB1*06); therefore, it can be concluded
      that the DRB1*04 and DQB1*02 alleles might be risk factors for the occurrence of
      HCC (OR = 4.373 and 3.807, respectively), and DQB1*06 may be a protective allele
      (OR = 0.259).

PMID- 18821215
TI  - Retinoid acid inhibits IL-1-induced iNOS, COX-2 and chemokine production in human
      chondrocytes.
AB  - This study aims to investigate the effects and mechanisms of all-trans retinoic
      acid (t-RA) on interleukin(IL)-1-induced production of several inflammatory
      mediators in human chondrocytes. The cartilage from OA patients receiving total
      knee or total hip replacement was obtained and chondrocytes were prepared.
      Chemokine concentrations were measured by ELISA. The expression of inducible
      nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) was determined by
      Western blotting and/or RT/PCR. Nitrite levels were measured by Griess assays.
      The DNA-binding activity and transcriptional activity of activator protein-1 (AP
      1) were measured by electrophoresis mobility shift assay and luciferase assay. We
      showed that t-RA suppressed IL-1-induced release of chemokines, including
      regulated upon activation, normal T cell expressed and secreted (RANTES),
      monocyte chemoattractant protein 2 (MCP-2), macrophage inflammatory protein
      1alpha (MIP-1alpha) and MIP-1beta. Four different retinoid derivatives all
      preserved inhibitory effects albeit the potency was different. t-RA potently
      suppressed IL-1-induced expression of iNOS and COX-2 and production of nitric
      oxide and prostaglandin E(2). In consistent with the results in primary
      chondrocytes, t-RA down-regulated IL-1-induced AP-1 DNA binding activity and
      transcriptional activity in a human fibroblast-like (commercially labeled as
      chondrocyte) cell line. By examining the effect of a c-jun N-terminal kinase
      (JNK) specific inhibitor, we showed that the suppression of JNK-AP-1 signaling
      was enough to inhibit IL-1-induced production of chemokines and activation of
      iNOS and COX-2 pathways. Collectively, our results raise a therapeutic option
      that intra-articular administration of retinoid derivatives at 10-1000 nanomolar
      concentrations may be effective to suppress the progression of inflammatory OA.

PMID- 18821216
TI  - Interleukin 8 is a surrogate marker for rapid diagnosis of bacteriuria.
AB  - Urinary tract infection (UTI) is one of the most common sources of infection in
      children under 5. Rapid diagnosis is a need to avoid complications of UTI. The
      goal of the present study was to evaluate the use of urinary interleukin 8 (IL8)
      as a rapid laboratory method for diagnosis of UTI. A total of 116 children were
      included in the study. They were complaining of different diseases with pyuria.
      In addition twenty healthy children were included as control subjects. Urine
      samples were subjected to full chemical, cytological and bacteriological
      examinations. In addition, urinary IL8 was measured. Patients showed
      significantly elevated urine IL-8 levels (80-820 pg/ml) compared to control
      subjects (6-10 pg/ml) (p < 0.0001). There was significant correlation between
      interleukin 8 level and white blood cells counts in urine (p = 0.039). The mean
      +/- SD of urinary IL-8 was significantly increased 165.8 +/- 115.1 in urine with
      bacterial growth (Staphylococcus species and Escherichia coli) p < 0.001 than in
      urine without growth. Urine with Escherichia coli (E. coli) growth had
      significantly higher IL 8 level than growth with other types of organisms. The
      sensitivity, specificity, accuracy, positive predictive value and negative
      predictive value had higher level for IL8 compared to other parameters in urine
      examination i.e., nitrite, WBCs and RBCs (85.7%, 60%, 64%, 87%, 64%
      respectively). This study highlights that bacteriuria is associated with higher
      level of urinary interleukin 8 than pyuria without bacteriuria. Thus from this
      study we can conclude that IL8 can be used as rapid surrogate marker for rapid
      laboratory diagnosis of urosepsis.

PMID- 18821217
TI  - Comparative study of interleukin-1beta expression by peripheral blood mononuclear
      cells and purified monocytes experimentally infected with Burkholderia
      pseudomallei and Burkholderia thailandensis.
AB  - Burkholderia pseudomallei is a causative agent of melioidosis. The present study
      investigated IL-1beta mRNA and protein expression by peripheral blood mononuclear
      cells and purified monocytes (n = 10) in response to infection with B.
      pseudomallei and B. thailandensis. Similarly increased IL-1beta mRNA and protein
      expression was found in both PBMC and purified monocytes stimulated with B.
      pseudomallei and B. thailandensis. Thus, this study suggests that IL-1beta
      response does not differ between infections with B. pseudomallei and its non
      virulent counterpart and other mechanisms may be involved in their distinct
      virulence in causing the disease.

PMID- 18821218
TI  - Altered immunodominance hierarchies of influenza A virus-specific H-2(b)
      restricted CD8+ T cells in the absence of terminal deoxynucleotidyl transferase.
AB  - Immunodominance is considered an obstacle to successful T cell-based vaccination,
      and constant efforts are made to uncover the underlying mechanisms for this
      phenomenon. We have examined the contribution of terminal deoxynucleotidyl
      transferase (TdT), whose function accounts for approximately 90% of T cell
      receptor diversity, to dominance hierarchies of H-2(b)-restricted flu-specific
      T(CD8+). Using intracellular cytokine staining to quantitatively detect epitope
      specific T(CD8+), we demonstrate that TdT-deficient mice exhibit a distinct
      hierarchical pattern in their primary and recall T(CD8+) responses to influenza A
      viruses, which results from skewed responsiveness towards select influenza
      epitopes. Our data establish a link between TdT and immunodominance in H-2(b)
      restricted antiviral T(CD8+) responses.

PMID- 18821219
TI  - Immunosuppressive properties of mesenchymal stem cells derived from bone marrow
      of patients with chronic myeloid leukemia.
AB  - Mesenchymal stem cells (MSCs) have emerged as excellent candidates for clinical
      application because of their capabilities of differentiating into multiple
      mesenchymal lineages and supporting hematopoiesis. Recently, MSCs have gained
      further interests after the demonstration of an immunosuppressive role. However,
      it is still unclear whether the immunosuppressive capability of MSCs will be
      altered with disease state. In this study, we obtained and expanded MSCs from
      bone marrow of patients with chronic myeloid leukemia (CML). Our results showed
      that MSCs derived from CML do not express costimulatory molecules CD40, CD80, and
      CD86. When MSCs derived from CML were added back to T cells stimulated by
      mitogens, a significant inhibition of T-cell proliferation was evident. MSCs
      differentiated into various mesenchymal lineages did not alter their
      immunosuppressive effect on T-cell proliferation. A significant T-cell inhibition
      was found in a transwell system, in which cell-cell contact between MSCs and
      effector cells was prevented. Furthermore, we found that transforming growth
      factor beta1 (TGF beta1) and hepatocyte growth factor (HGF) were major mediators
      of T-cell suppression by MSCs derived from CML. These results demonstrated that
      autologous MSCs derived from CML could effectively suppress T-cell proliferation.

PMID- 18821220
TI  - Scrophularia buergeriana regulates cytokine production in vitro.
AB  - The Scrophularia buergeriana (SB) has long been used to treat various diseases an
      account of its antimicrobial and anti-virus activity. However, it is unclear how
      SB regulates the immune responses. This study investigated the effect of SB on
      the production of cytokines in a human T-cell line, MOLT-4 cells, and mouse
      peritoneal macrophages. The MOLT-4 cells were cultured for 24 h in the presence
      or absence of SB plus concanavalin (con) A. SB plus con A significantly increased
      the level of interleukin (IL)-2, IL-4 and interferon (IFN)-gamma production
      compared with that of con A alone (approximately 1.79-fold for IL-2, 2-fold for
      IL-4, and 1.85-fold for IFN-gamma, p < 0.05). SB plus recombinant IFN-gamma (rIFN
      gamma) increased the level of IL-12 and NO production compared with rIFN-gamma
      alone. In addition, SB plus rIFN-gamma increased the level the iNOS expression on
      mouse peritoneal macrophages. Overall, SB may have an immune-enhancement effect
      through cytokine production.

PMID- 18821221
TI  - Advances in pediatric audiological and vestibular disorders.

PMID- 18821222
TI  - Genetics of congenital hearing impairment: a clinical approach.
AB  - Hearing impairment (HI) is the most frequent sensory disorder, with a genetic
      etiology in >50% of all cases, due to mutations in >44 identified genes.
      Autosomal recessive inheritance explains the majority, with GJB2 (connexin 26)
      mutations accounting for 15-50% of paediatric HI. Delayed presentation of HI to
      11-60 months in cases of biallelic GJB2 mutations is a concern, necessitating a
      good audiological follow-up in addition to neonatal hearing screening. Providing
      a genetic diagnosis in congenital HI has implications for the prognosis, the
      possible risk of associated medical manifestations, and precise genetic
      counseling of the family, and should be integrated into the medical examinations
      done in order to diagnose syndromic features. Large-scale mutation detection
      methods, such as micro arrays, are promising for wider genetic testing, but few
      studies on their clinical utility have been published, so far. Limitations of
      interpretation of genetic test results, combined with significant ethical issues,
      currently do not justify to institute genetic screening for GJB2 mutations in
      neonates before a diagnosis of HI is established.

PMID- 18821223
TI  - Current considerations in pediatric speech audiometry.
AB  - Current considerations in pediatric speech perception assessment are highlighted
      in this article with a focus on specific test principles and variables that must
      be addressed when evaluating speech perception performance in children. Existing
      test materials are reviewed with an emphasis on the level of sensitivity and
      standardization that they have for accurate assessment of a child's speech
      perception performance. A test battery approach is advocated because speech
      perception is an abstract construct, and in order to provide a comprehensive
      assessment of a child's capabilities, information is needed from several sources
      of concrete data. The importance of ongoing speech perception assessment in
      children is also emphasized because a child's progress over time must be
      monitored to determine if improvements need to be made with amplification and
      intervention efforts. Results from pediatric speech perception assessments can
      provide practical information regarding the prognosis of speech, language,
      reading, and cognitive abilities of children as well as steps that need to be
      taken in the intervention process.

PMID- 18821224
TI  - The bone-anchored hearing aid for children: recent developments.
AB  - In 1984 the Bone-Anchored Hearing Aid, or BAHA, system was introduced. Its
      transducer is coupled directly to the skull percutaneously to form a highly
      effective bone-conduction hearing device. Clinical studies on adults with
      conductive hearing loss have shown that the BAHA system outperforms conventional
      bone-conduction hearing aids. Therefore, the next step was to apply the BAHA
      system in children with congenital or acquired conductive hearing loss. Reviewed
      data showed that, on average, such children benefited significantly more from the
      BAHA than from reconstructive surgery. Thus, BAHA application appears to be the
      best option to achieve normal communication and speech and language development
      in children with bilateral conductive hearing loss. However, in children under
      the age of three to four years, a conventional solution must be applied, e.g. a
      bone conductor with a transcutaneous coupling, because they are too young to
      undergo BAHA implant surgery. In the case of unilateral congenital conductive
      hearing loss, there is no convincing evidence in the clinical literature for
      early intervention. In summary, the BAHA system can be considered a new,
      indispensable tool for children with bilateral conductive hearing loss.

PMID- 18821225
TI  - Immune-mediated audiovestibular disorders in the paediatric population: a review.
AB  - Recent studies show that several audiovestibular pathologies in the paediatric
      population may be immune-mediated. This is even more probable if the pathology is
      associated with a coexisting systemic autoimmune disorder. At this time, however,
      the current literature is limited to a few case reports, and little is known with
      regard to prevalence, diagnosis, and management of immune-mediated inner-ear
      disorders in children. This review aims to shed some light on clinical
      presentation, diagnosis, and treatment of paediatric immune-mediated inner-ear
      disorders. Sudden and progressive sensorineural hearing loss is discussed, in
      addition to some of the systemic autoimmune disorders commonly associated with
      immune-mediated audiovestibular pathology such as Cogan's syndrome, systemic
      lupus erythematosus, Behcet's disease, Sjogren's syndrome, and juvenile
      idiopathic arthritis.

PMID- 18821226
TI  - Development and assessment of the vestibular system.
AB  - Paediatric vestibular assessment is necessary in various situations, yielding
      invaluable information relating to diagnoses and allowing for the formulation of
      appropriate rehabilitative strategies when considering the management of children
      with vestibular and balance problems, alone or in association with hearing
      impairment or other developmental disorders. The development and assessment of
      the vestibular system is considered in this article.

PMID- 18821227
TI  - Vestibular disorders in children.
AB  - When vertigo and dizziness are diagnosed in a child, this is a matter of concern
      for the physician and the child's family. Prior to a comprehensive otological,
      neurological, and vestibular clinical examination, physicians often request CT or
      MRI scanning, although in most cases such expensive testing is unnecessary. The
      present work is based on the results of a 14-year study conducted with a sample
      of more than 2,000 children referred for vertigo and balance disorders to the
      functional vestibular evaluation unit of the ENT pediatric department at Robert
      Debre Hospital (Paris). The clinical signs of vestibular deficit and the most
      frequent aetiologies of vertigo and dizziness in children are detailed (migraine
      equivalent, ophthalmologic disorders, benign paroxysmal idiopathic pediatric
      vertigo, and temporal bone fracture), which has been helpful in determining the
      best diagnostic procedure and therapy for vertigo in children.

PMID- 18821228
TI  - Balance and otitis media with effusion.
AB  - Dizziness can be caused by a variety of peripheral vestibular, central, and
      systemic disease processes. Eustachian tube dysfunction with and without middle
      ear effusion has been considered one of the most common causes of balance
      disturbances in young children. Several studies have indicated that during an
      episode of otitis media the child's balance deteriorates and the child may become
      clumsy and fall more often. Thus, not only the adverse effect on hearing should
      be considered in the management of a child with otitis media, but also the
      child's balance.

PMID- 18821229
TI  - Vestibular failure in children with congenital deafness.
AB  - Congenitally deaf infants and children commonly suffer vestibular failure in both
      ears, and impairment of postural control, locomotion, and gait. The development
      of gross motor functions, such as head control, sitting, and walking is likely to
      be delayed, but fine motor function is usually preserved unless disorders of the
      central nervous system are present. These children can eventually catch up with
      their normal peers in terms of development and growth as a result of central
      vestibular compensation. The visual and somatosensory systems, pyramidal and
      extrapyramidal motor system (cerebellum, basal ganglia, cerebrum) and
      intellectual development, compensate for vestibular failure in infants and
      children with congenitally hypoactive or absent function of the semicircular
      canals and otolith organs.

PMID- 18821230
TI  - Dysarthria impact profile: development of a scale to measure psychosocial
      effects.
AB  - BACKGROUND: The psychosocial impact of acquired dysarthria on the speaker is well
      recognized. To date, speech-and-language therapists have no instrument available
      to measure this construct. This has implications for outcome measurement and for
      planning intervention. This paper describes the Dysarthria Impact Profile (DIP),
      an instrument that has the potential to meet this need in clinical practice.
      AIMS: To describe the development of the DIP, which was devised as part of a
      larger study to measure psychosocial impact of acquired dysarthria from the
      speaker's perspective. METHODS & PROCEDURES: The current psychometric properties
      of the DIP are examined. The scale was administered to 31 participants with
      acquired dysarthria. The internal consistency of the scale items and their intra
      rater reliability were investigated. Concurrent validity was assessed for the
      portion of the scale (Section A) assessing impact of acquired dysarthria on self
      perception, self-concept and self-esteem by comparing the results with changes in
      self-concept as determined by the Head Injury Semantic Differential Scale (HISD
      II). OUTCOMES & RESULTS: The DIP shows good internal consistency and strong intra
      rater reliability overall. There was a strong, statistically significant,
      correlation between results on Section A of the DIP and the results of the HISD
      II suggesting convergent validity for this portion of the scale. There are some
      limitations to the scale in its current format and these are highlighted.
      CONCLUSIONS & IMPLICATIONS: The scale is now ready for further refinement and
      development. Once validated, it should act as a robust outcome measure for
      clinicians.

PMID- 18821231
TI  - Toxic/hazardous substances & environmental engineering. Foreword.

PMID- 18821232
TI  - Development of a fluorescence in situ hybridization protocol for the
      identification of micro-organisms associated with wastewater particles and flocs.
AB  - Fluorescence in situ hybridization (FISH) provides a unique tool to study micro
      organisms associated with particles and flocs. FISH enables visual examination of
      micro-organisms while they are structurally intact and associated with particles.
      However, application of FISH to wastewater and sludge samples presents a specific
      set of problems. Wastewater samples generate high background fluorescence due to
      their organic and inorganic content making it difficult to differentiate a probe
      conferred signal from naturally fluorescing particles with reasonable certainty.
      Furthermore, some of the FISH steps involve harsh treatment of samples, and are
      likely to disrupt the floc structure. This study developed a FISH protocol for
      studying micro-organisms that are associated with particles and flocs. The
      results indicate that choice of a proper fluorochrome and labeling technique is a
      key step in reducing the background fluorescence and non-specific binding, and
      increasing the intensity of the probe signal. Compared to other fluorochromes
      tested, CY3 worked very well and enabled the observation of particles and debris
      in red and probe signal from microbes in yellow. Fixation, hybridization, and
      washing steps disturbed the floc structure and particle-microbe association.
      Modifications to these steps were necessary, and were achieved by replacing
      centrifugation with filtration and employment of nylon filters. Microscope slides
      generated excellent quality images, but polycarbonate membrane filters performed
      better in preserving the floc structure.

PMID- 18821233
TI  - A simple image analysis algorithm for evaluation of extended filaments length
      based on the enhanced digitized image.
AB  - An automated image analysis procedure was developed to determine extended
      filaments length and floc area to evaluate settling characteristics of activated
      sludge. Digitized image obtained by Gram staining granted the first step of
      algorithm, segmentation, to be extremely clear and simple. The image analysis
      work could become more accurate and less time consuming one to be required only 1
      minute of operation time per image. Filamentous bulking phenomenon of the
      biological sludge was induced in a laboratory-scale bioreactor system under an
      extreme operational condition, and the non-bulking and filamentous bulking sludge
      samples captured were examined with image analysis as well as traditional
      settling test. There existed a linear relationship between DSVI (Diluted Sludge
      Volume Index) and the extended filaments length. Similar results were also
      obtained with the extended filaments per floc area. The arithmetic mean extended
      filaments length showed an excellent linearity with the DSVI. It is believed that
      the image analysis algorithm developed in this study can be utilized for
      estimation of the extended filaments length and for evaluation of the settling
      characteristics of activated sludge effectively.

PMID- 18821234
TI  - Isolation and molecular identification of extracellular polymeric substances
      (EPS) producing bacterial strains for sludge settling and dewatering.
AB  - One of the major problems in overall wastewater treatment process is sludge
      settling and dewatering. In general, sludge settling and dewatering is carried
      out using conventional physico-chemical methods that are known to be expensive,
      and these processes further increase the sludge volume and ultimate disposal
      costs. To overcome this problem, a suitable alternative could be the use of
      bioflocculants for sludge settling and dewatering. To achieve bioflocculation,
      extracellular polymeric substances (EPS) producing bacterial strains were
      isolated from the complex microbial community of wastewater sludge. Crude EPS
      produced in the form of bacterial broth was used to test kaolin flocculation
      activity. Three out of 10 bacterial strains (B2, B8 and B9) were pre-selected for
      sludge settling. Based on sludge settling and dewatering results, B8 possessed
      better flocculating property than other bacterial strains. These sludge
      microorganisms were identified based on their 16S rDNA sequences and bacterial
      strain B8 was identified as Serratia sps.

PMID- 18821235
TI  - Identification of Archaeal population in the granular sludge of an UASB reactor
      treating sewage at low temperatures.
AB  - Effect of low temperature on up-flow anaerobic sludge bed (UASB) reactor
      performance treating raw sewage was investigated in terms of the variations in
      methanogenic diversity using the 16S rRNA based Fluorescence In-Situ
      Hybridization (FISH) technique. The diversity of microorganisms present in the
      anaerobic granular sludge and the structure of the granules operated at 13
      degrees C have been investigated using FISH combined with CSLM (Confocal Scanning
      Laser Microscopy). According to FISH results, archaeal cells representing
      methanogens were found intensively dominant in the bottom sampling port of the
      UASB reactor and acetoclastic Methanosaeta was the abundant methanogen. Other
      methanogens such as Methanosarcina and Methanobacterium like species were also
      observed. The abundance of originally mesophilic Methanosaeta-related Archaea
      under low temperature at all sampling days revealed the microbial adaptation to
      psychrophilic conditions. This might be attributed to the enzymatic alterations
      in Methanosaeta cells originating from seed sludge, which were exposed to sub
      mesophilic temperatures at start-up and then to psychrophilic conditions during
      gradual decreases of temperature. According to CSLM observation, even though the
      sludge retained in the reactor kept its granular form as a whole, the majority of
      the granules had a tendency to be partly broken and they lost their rigidity when
      raw sewage was fed following synthetic sewage. Besides, Methanosaeta related
      species prevailing in seed sludge have noticeably lost their long filamentous
      forms and deteriorated during raw sewage feeding. Members of the order
      Methanobacteriales constituted the major hydrogenothrophic methanogens present in
      the psychrophilic UASB reactor, whereas the other hydrogenothrophic methanogens-
      members of the order Methanococcales and Methanogenium relatives--were absent.

PMID- 18821236
TI  - Extraction of nonylphenol and nonylphenol ethoxylates from sewage sludge using
      the pressurized fluid extraction method and the supercritical fluid extraction
      method.
AB  - To establish endocrine disruptor (ED) monitoring and control methods for
      wastewater treatment plants, it is necessary to clarify the fate of EDs in each
      process of a sludge treatment system. However, the ED analysis method for sewage
      sludge containing large quantities of organic matters has not been established.
      So, a highly reliable analytical method that accurately measures EDs in sewage
      sludge must be developed. This paper reports on the results of applying the
      Pressurized Fluid Extraction (PFE) method and the Supercritical Fluid Extraction
      (SFE) method to the extraction of nonylphenol (NP) and nonylphenol ethoxylate
      (NPnEO) existence of which has often been confirmed in past surveys. To clarify
      the quantity of EDs in sludge specimens and the fate of EDs in the sludge
      treatment process, appropriate analytical methods should be developed. In this
      study, the PFE method and the SFE method were tested to extract NP and NPnEO from
      sewage sludge specimens. The findings indicate that the extraction from dried
      sludge by the PFE method can extract a larger quantity of NP and NPnEO in a
      shorter time than the widely used heating reflux method. Regarding the extraction
      by the SFE method, conditions for extraction of NP and NPnEO at a higher rate
      than the heating reflux method were not found.

PMID- 18821237
TI  - Pipe flow of highly concentrated sludge.
AB  - Industries that pump sludges experience pressure to operate at higher
      concentrations with sludges that have high mechanical strength properties. The
      viscous character of the sludge becomes increasingly non-Newtonian and yield
      stress in nature. The two principal problems are regime determination and laminar
      flow settling, which ultimately results in pipe blockage. In facing the
      diversities that sludge management currently presents, it is important to resolve
      these issues and develop solutions for engineering practice. The approaches
      developed at the Flow Process Research Centre to deal with these problems are
      introduced. The objectives of this paper are to introduce experimental data of
      the phenomena associated with the pipe flow of highly concentrated sludge, and
      use these to develop and evaluate predictive modeling approaches suitable for
      engineering design purposes. For the prediction of transitional flow, a new
      general approach for visco-plastic fluids in industrially relevant pipe sizes is
      presented, based on dimensional analysis of the flow problem. Settled bed
      behavior is modeled using an adapted two-layer model approach, in all flow
      regimes. The modeling approaches are evaluated using the experimental results
      obtained. The analysis shows that the present work provides a workable solution
      for the prediction of the pipe flow of highly concentrated sludges, for
      engineering design purposes.

PMID- 18821238
TI  - Chemical sludge conditioning in combination with different conventional and
      alternative dewatering devices: chamber filter press, decanter and Bucher press.
AB  - The Kemicond process for sludge conditioning consists of chemical treatment with
      sulphuric acid and hydrogen peroxide at a pH-value of approximately 4 followed by
      a dewatering unit. It is shown that chemical treatment can improve the
      dewaterability of ferruginous digested sludge. It is concluded that the Fenton
      process as well as the oxidation of organics and the formation of iron hydroxo
      complexes are important reaction mechanisms. Furthermore, the organic matter
      changes through the acidic oxidative process. With the improvement in
      dewaterability, it is possible to achieve an increase in TS concentration, which
      affects a reduction of the sludge volume. Cost savings for sludge disposal can
      amortize the additional investment and operational costs for chemical treatment.

PMID- 18821239
TI  - Aerobic and anaerobic bioprocessing of activated sludge: floc disintegration by
      enzymes.
AB  - Hydrolytic enzymes such as glucosidases, lipases, and proteases have an
      imperative function at the hydrolysis stage of complex organic structures in the
      degradation of biodegradable particulate organic matter. As a key factor,
      extracellular polymeric substances (EPS) control the extracellular hydrolytic
      enzymes in this degradation mechanism. A flocculated matrix of EPS bridging with
      bacteria holds back the dewaterability properties of the bioprocessed sludges.
      Disruption of the flocculated matrix leads to improved solubilization of sludge
      solids by attacking the hydrolytic enzymes to polymeric substances forming enzyme
      substrate complexes. To determine the floc disintegration mechanisms by enzymes
      during aerobic and anaerobic bioprocessing of sludges, experimental data obtained
      from three aerobic digesters and three anaerobic digesters were evaluated. As
      part of a broader project examining the overall fate and effects of hydrolytic
      enzymes in biological sludge stabilization, this paper compares the performances
      of aerobic and anaerobic reactors used in this study and reports significant
      improvements in enzymatic treatment of activated sludge.

PMID- 18821240
TI  - Enhanced efficiency of industrial-scale anaerobic digestion by the addition of
      glycosidic enzymes.
AB  - The results of the action of two glycosidic enzymes added to an anaerobic
      digester processing mixed wastewater sludge are reported in this paper. The
      experiment was performed at a continuously operating full-scale wastewater
      treatment plant during a 6-month period. The addition of the enzyme mixture
      resulted in improved gas production and dewatering properties. Dewatering
      experiments, both on enzyme-treated and reference sludge on the local
      centrifuges, indicated that the carbonaceous matter was decreased by 7% in enzyme
      treated sludge, and the average dry solids increased from 27% (reference) to 31%
      in enzyme-treated sludge. The polymer dosage was decreased from 8 to 5 kg/t dry
      solids. Additionally, practical experiences were gathered concerning the
      transformation from static laboratory-scale batch experiments to a dynamic
      continuous industrial scale setup. Preliminary cost calculations showed
      beneficial aspects and economical feasibility of enzyme addition to an anaerobic
      sludge digestion process.

PMID- 18821241
TI  - Improving anaerobic and aerobic degradation by ultrasonic disintegration of
      biomass.
AB  - Biological cell lysis is known to be the rate-limiting step of anaerobic
      biosolids degradation. Due to the slow pace by which this reaction occurs, it is
      necessary to equip treatment plants with large digesters or alternatively
      incorporate technological aids. High-power ultrasound used to disintegrate
      bacterial cells has been utilized as a pre-treatment process prior to anaerobic
      digestion. Through this application, as seen on pilot- and full-scales, it is
      possible to attain up to 30% more biogas, an increase in VS-destruction of up to
      30% and a reduced sludge mass for disposal. Utilizing ultrasound technology in
      aerobic applications is a new and innovative approach. Improved denitrification
      through a more readily available internal carbon source, and less excess sludge
      mass can be traced to the positive effects that sonication of sludge has on the
      overall biological wastewater treatment process. Reference full-scale
      installations suggest that the technology is both technically feasible and
      economically sound.

PMID- 18821242
TI  - Ozone treatment of wastewater sludge for reduction and stabilization.
AB  - Ozonation was applied to wastewater sludge for reduction and stabilization. Ozone
      was found to be very effective at reducing sludge and producing a useful carbon
      source. An ozone dose of 0.3 g/gDS fulfilled the criteria for the disinfection of
      class A type biosolids. The sludge treated with 0.5 gO(3)/gDS produced no
      hydrogen sulfide for a month at 29 degrees C. Ozonation resulted in low pH
      conditions, which might facilitate the mobilization of heavy metals from sludge.
      The results of a geotechnical investigation proved that the residuals of ozone
      treated sludge did not meet the required properties required for landfill cover
      without the addition of quick lime.

PMID- 18821243
TI  - Impact of initial biodegradability on sludge anaerobic digestion enhancement by
      thermal pretreatment.
AB  - Thermal treatments with temperature ranging from 60 to 210 degrees C were applied
      to 6 waste-activated sludge samples originating from high or medium load,
      extended aeration wastewater treatment processes that treated different
      wastewaters (urban, urban and industrial or slaughterhouse). COD sludge
      solubilisation was linearly correlated with the treatment temperature on the
      whole temperature range and independently of the sludge samples. Sludge batch
      mesophilic biodegradability increased with treatment temperature up to 190
      degrees C. In this temperature range, biodegradability enhancement or methane
      production increase by thermal hydrolysis was shown to be a function of sludge
      COD solubilisation but also of sludge initial biodegradability. The lower the
      initial biodegradability means the higher efficiency of thermal treatment.

PMID- 18821244
TI  - Sludge treatment and reuse considering different climates and varying other
      conditions--export-oriented research for developing and threshold countries.
AB  - Sewage sludge accumulating during biological wastewater treatment has to be
      treated appropriately to avoid impacts on the environment and risks to public
      health. Especially pathogen reduction is necessary when sludge is disposed or
      reused in such a way that human contact is possible. In industrialized countries
      various sludge treatment technologies are available, but these are often only
      approved under local conditions. When exporting these technologies and
      experiences to other countries, a number of factors have to be taken into account
      including climatic, sociocultural, political and financial aspects. This paper
      gives an overview of current knowledge regarding sewage sludge treatment in
      developing countries. Various sanitation projects are realized worldwide and
      experiences from these plants already in operation are summarized. Results of on
      going laboratory experiments in climatic chambers regarding aerobic and anaerobic
      stabilization as well as lime treatment are shown to define the best-practicable
      sludge treatment technology for a certain climate. Options for final reuse or
      disposal are presented depending on end-product quality.

PMID- 18821245
TI  - Optimization of the preparation conditions of ceramic products using drinking
      water treatment sludges.
AB  - The aim of this work is to optimize, via Response Surface Methodology, the values
      of the main process parameters for the production of ceramic products using
      sludges obtained from drinking water treatment in order to valorise them. In the
      first experimental stage, sludges were collected from a drinking water treatment
      plant for characterization. In the second stage, trials were carried out to
      elaborate thin cross-section specimens and fired bricks following an orthogonal
      central composite design of experiments with three factors (sludge composition,
      grain size and firing temperature) and five levels. The optimization parameters
      (Y(1)=shrinking by firing (%), Y(2)=water absorption (%), Y(3)=density (g/cm(3))
      and Y(4)=compressive strength (kg/cm(2))) were determined according to
      standardized analytical methods. Two distinct physicochemical processes were
      active during firing at different conditions in the experimental design,
      preventing the determination of a full response surface, which would allow direct
      optimization of production parameters. Nevertheless, the temperature range for
      the production of classical red brick was closely delimitated by the results;
      above this temperature, a lightweight ceramic with surprisingly high strength was
      produced, opening possibilities for the valorisation of a product with
      considerably higher added value than what was originally envisioned.

PMID- 18821246
TI  - Odor-causing volatile organic compounds in wastewater treatment plant units and
      sludge management areas.
AB  - Odors due to malodorous gas and vapor emissions from units of Izmir Wastewater
      Treatment Plant (WWTP) were studied and evaluated with respect to chemical
      composition. Altogether 29 target compounds consisting of 4 different groups of
      chemicals were identified and quantified in the odorous gas samples from
      wastewater and sludges. Total volatile malodorous organic compounds (VMOC)
      consisted of reduced sulfur compounds (RSCs) and different volatile organic
      compounds (VOCs) including volatile organic compounds (VOCs), aldehydes,
      monoaromatics (BTX) and some halogenated organics. Among these components the
      most abundant group was the monoaromatics (69% of the total VOC). A statistically
      significant linear relationship was found between odor concentrations determined
      by olfactometry and total VOC concentrations (r(2)=0.89, n=5, P<0.05) in the
      samples of odorous gases. Based on the odor contribution ratios of the compounds
      studied, the results of the study revealed that hydrogen sulfide, propanal and
      toluene were dominating in the odor emissions and these were explaining 99% of
      the variability in odor concentrations (r(2)=0.99, n=5, P<0.05). It was shown
      that not only the hydrogen sulfide and RSCs but also other organics were
      important in forming the odors from sludge units and sludge management areas.

PMID- 18821247
TI  - Recent findings on biosolids cake odor reduction--results of WERF phase 3
      biosolids odor research.
AB  - The Water Environment Research Foundation (WERF) has sponsored three phases of a
      long-term project entitled "Identifying and Controlling Odors in the Municipal
      Wastewater Environment." The current (third) phase focuses on reduction of odors
      from dewatered biosolids cakes, and is entitled "Biosolids Processing
      Modifications for Cake Odor Reduction." This phase encompasses nine research
      agenda items developed from the results of the prior phase of research (Phase 2),
      which was completed in December 2003 as WERF Report No. 00-HHE-5T and was
      entitled "Impacts of In-Plant Parameters on Biosolids Odor Quality." The current
      phase (Phase 3) was a 2.5-year project, the first half of which was dedicated to
      testing several of the more promising hypotheses from Phase 2 in the laboratory
      to help determine the cause-effect relationships of odor generation from
      biosolids, and to develop odor reduction techniques. It is important to note that
      this research project covers the reduction or prevention of odorous emissions
      from dewatered biosolids cake, not odor control by means of containment or
      adsorption or absorption of malodorous emissions. In the remainder of the Phase 3
      project, promising laboratory findings are being applied to biosolids handling
      processes at one or more wastewater treatment plants (WWTPs), with the goal of
      achieving significant cake odor reduction in a realistic, full-scale setting. The
      Phase 3 laboratory results were used to identify the relative effectiveness of
      methods for reducing biosolids cake odors, using techniques and measurements of
      biosolids cake odor production potential that have been developed by the WERF
      Project Team. Plans to demonstrate the most promising research findings at full
      scale biosolids digestion and dewatering facilities constitute the final, fourth
      phase of the project. Contacts have been made with wastewater treatment
      facilities that have an interest or need to reduce their biosolids cake odors.
      The main goal of the next phase of the project will be to match wastewater or
      biosolids facilities that need to reduce biosolids odors with specific
      technologies, chemicals, or biological agents, in order to demonstrate the
      efficacy of promising laboratory findings full scale at a real WWTP.

PMID- 18821248
TI  - Proceedings of the 16th annual conference of the Groupement des Pharmacochimistes
      de l'Arc Atlantique (GP2A).

PMID- 18821249
TI  - 3D Pharmacophore, hierarchical methods, and 5-HT4 receptor binding data.
AB  - 5-Hydroxytryptamine subtype-4 (5-HT(4)) receptors have stimulated considerable
      interest amongst scientists and clinicians owing to their importance in
      neurophysiology and potential as therapeutic targets. A comparative analysis of
      hierarchical methods applied to data from one thousand 5-HT(4) receptor-ligand
      binding interactions was carried out. The chemical structures were described as
      chemical and pharmacophore fingerprints. The definitions of indices, related to
      the quality of the hierarchies in being able to distinguish between active and
      inactive compounds, revealed two interesting hierarchies with the Unity (1 active
      cluster) and pharmacophore fingerprints (4 active clusters). The results of this
      study also showed the importance of correct choice of metrics as well as the
      effectiveness of a new alternative of the Ward clustering algorithm named Energy
      (Minimum E-Distance method). In parallel, the relationship between these
      classifications and a previously defined 3D 5-HT(4) antagonist pharmacophore was
      established.

PMID- 18821250
TI  - Molecular modelling of phthalates - PPARs interactions.
AB  - Di(2-ethylhexyl) phthalate (DEHP) is the most widely plasticizer for polyvinyl
      chloride (PVC) that is used in plastic tubes, in medical and paramedical devices
      as well as in food storage packaging. The toxicological profile of DEHP has been
      evaluated in a number of experimental animal models and has been extensively
      documented. Its toxicity is in part linked to the activation of the peroxisome
      proliferator-activated receptor alpha (PPAR(alpha)). As a response, an intensive
      research for a new, biologically inert plasticizer has been initiated. Among the
      alternative studied, tri(2-ethylhexyl) trimellitate (TEHTM) or trioctyl
      trimellitate (TOTM) has attracted increasing interest. However, very little
      information is available on their biological effects. We proceeded to dock TOTM,
      DEHP and its metabolites in order to identify compounds that are likely to
      interact with PPAR(alpha) and PPAR(gamma) binding sites. The results obtained
      hint that TOTM is not able to bind to PPARs and should therefore be safer than
      DEHP.

PMID- 18821251
TI  - Synthesis of new 1-[2-Azido-2-(2,4-dichlorophenyl)ethyl]-1H/-imidazoles and in
      vitro evaluation of their antifungal activity.
AB  - New 1-[2-azido-2-(2,4-dichlorophenyl)ethyl]-1H/-imidazole were synthesized by
      nucleophilic substitution of various tertiary alcohols with azide anion in
      presence of boron trifluoride-diethyl etherate. Their antifungal activity was
      evaluated against Candida albicans, Candida glabrata, Aspergillus fumigatus and
      an azole-resistant petite mutant of C. glabrata. Preliminary SAR results are
      discussed.

PMID- 18821252
TI  - PAMAM dendrimers for the delivery of the antibacterial Triclosan.
AB  - Many oral care products incorporate an antibacterial compound to prevent the
      formation of dental plaque which predisposes teeth to dental caries or
      periodontal disease. Triclosan (TCN) is a commonly used antiplaque agent in
      toothpastes. Strategies to increase the delivery efficiency of antibacterials
      using formulation aids such as polyamidoamine (PAMAM) dendrimers are of interest.
      Solubilisation studies over the pH range 5-12 demonstrated an increase in the
      level of TCN solubilised with increasing dendrimer concentration (1 mM-5 mM).
      However, the dendrimer was unable to enhance TCN solubility at lower pH values
      and the solubilising effect observed was attributed to the ionization of TCN (pKa
      8.14) resulting from dendrimer induced pH changes. End group modification of G3
      PAMAM dendrimer with phenylalanine in order to promote solubility through pi-pi
      stacking between TCN and the amino acid has been carried out. Phenylalanine:G3
      PAMAM conjugates of different ratios (32:1, 21:1, 16:1) were synthesized. The
      fully conjugated dendrimer (32:1) had poor aqueous solubility, whereas the 21:1
      and 16:1 dendrimer conjugates were water soluble. The 21:1 conjugate was tested
      for its ability to solubilise TCN, however, again there was no increase over
      control buffer solutions of the same pH. An alternative approach under
      investigation is to directly conjugate TCN to PAMAM dendrimers via a hydrolysable
      linkage.

PMID- 18821253
TI  - Synthesis and antitumour evaluation of novel 2-phenylbenzimidazoles.
AB  - A new series of fluorinated and non-fluorinated 2-phenylbenzimidazoles bearing
      oxygenated substituents on the phenyl ring has been synthesized. Synthesis of the
      new series was based on our previous discovery of 2-(3,4-dimethoxyphenyl)-5
      fluorobenzothiazole (PMX 610) as a potent and selective antitumour agent in vitro
      (sub-nanomolar GI(50) in sensitive human cancer cell lines), but with poor
      aqueous solubility and lack of a definitive cellular target limiting further
      development. In this study we test the hypothesis that 2-phenylbenzimidazoles
      with similar substitution patterns to PMX 610 would retain potent antitumour
      activity but with potentially superior pharmaceutical properties. In general the
      new compounds were less active than the former benzothiazole series in vitro when
      tested against the breast cancer cell lines MCF-7 and MDA 468; however the two
      most active compounds in the present series (3j and 3k) exhibit low micromolar
      GI(50) values in both cell lines and provide the opportunity for further chemical
      derivatization with a view to target identification.

PMID- 18821254
TI  - Synthesis of new pyrrolo[1,2-a]quinoxaline derivatives as potential inhibitors of
      Akt kinase.
AB  - Akt kinases are attractive targets for small molecule drug discovery because of
      their key role in tumor cell survival/proliferation and their
      overexpression/activation in many human cancers. Recent efforts in the
      development and biological evaluation of small molecule inhibitors of Akt have
      led to the identification of novel Akt kinase inhibitors, based on a quinoxaline
      or pyrazinone scaffold. A series of new substituted pyrrolo[1,2-a]quinoxaline
      derivatives, structural analogues of these active quinoxaline or pyrazinone
      pharmacophores, was synthesized from various substituted 2-nitroanilines or 1,2
      phenylenediamine via multistep heterocyclization process. These new compounds
      were tested for their in vitro ability to inhibit the proliferation of the human
      leukemic cell lines K562, U937 and HL60, and the breast cancer cell line MCF7.
      Three of these human cell lines (K562, U937 and MCF7) exhibited an active
      phosphorylated Akt form. The most promising active pyrroloquinoxalines were found
      to be 1a that inhibited K562 cell line proliferation with an IC(50) of 4.5
      microM, and 1h that inhibited U937 and MCF7 cell lines with IC(50) of 5 and 8
      microM, respectively. These two candidates exhibited more potent activities than
      the reference inhibitor A6730.

PMID- 18821255
TI  - Synthesis and immunosuppressive activity evaluation of substituted N-imidazolidin
      2-ones and N-tetrahydropyrimidin-2(1H)-ones.
AB  - Seventeen compounds with either an imidazolin-2-one or a tetrahydropyrimidin
      2(1H)-one scaffold were synthesized and evaluated for their immunosuppressive
      activity in a concanavallin A (ConA)-stimulated mouse splenocytes proliferation
      test. Three of these molecules exerted a significant activity at 90 microM. All
      the compounds of the tetrahydropyrimidin-2(1H)-one series have turned out to be
      inactive showing the crucial role of the imidazolidin-2-one scaffold in the
      induction of an immunosuppressive activity.

PMID- 18821256
TI  - Beta-lactam type molecular scaffolds for antiproliferative activity: synthesis
      and cytotoxic effects in breast cancer cells.
AB  - A series of novel beta-lactam containing compounds are described as
      antiproliferative agents and potential selective modulators of the oestrogen
      receptor. The purpose of the study is to evaluate the antiproliferative effects
      of these compounds on human MCF-7 and MDA MB-231 breast cancer cells. The
      compounds are designed to contain three aryl ring substituents arranged on the
      heterocyclic azetidin-2-one (beta-lactam), thus providing conformationally
      restrained analogues of the triarylethylene arrangement exemplified in the
      tamoxifen type structure. The compounds demonstrated potency in antiproliferative
      assays against MCF-7 human breast cancer cell line at low micromolar to nanomolar
      concentrations with low cytotoxicity and moderate binding affinity to the
      oestrogen receptor. The effect of a number of aryl and amine functional group
      substitutions on the antiproliferative activity of the beta-lactam products was
      explored and a brief computational structure-activity relationship investigation
      with molecular simulation was investigated.

PMID- 18821257
TI  - Side chain modifications of (indol-3-yl)glyoxamides as antitumor agents.
AB  - New series of analogues of N-(pyridin-4-yl)-2-[1-(4-chlorobenzyl)-indol-3
      yl]glyoxamide D-24851 were synthesized, characterized and tested for their in
      vitro anticancer properties. In the first series, an amino acid spacer was
      introduced in the glyoxamide chain of D-24851. In the second series, the
      glyoxamide chain was moved to positions 4 and 5 of indole skeleton. These new
      compounds were tested on four cancer cell lines (KB, SK-OV-3, NCI-H460 and SF
      268), with promising activity for the glycine derivative.

PMID- 18821258
TI  - Synthesis and biological evaluation of new donepezil-like Thiaindanones as AChE
      inhibitors.
AB  - Pharmacomodulations of previously reported thiaindanones related to donepezil
      were achieved with the aim to enhance their AChE inhibitory activity.
      Condensation of the cyclopentane carbonyl group into hydrazone or cyanolefine
      derivatives, as well as its hydrogenation and the subsequent substitution of the
      resulting hydroxyl group led to new 2-(4-benzylpiperazin-1-yl)-N-(1,3-dibromo-6
      hydroxy-5,6-dihydro-4H-cyclopenta[c]thien-4-yl) acetamides. The in vitro
      evaluation of this new series, according to the method of Ellman, shows however
      that it conserved only partially the biological activity. The best compound
      remains the alcohol 11 (IC(50) = 0.40 microM, against 0.02 microM for donepezil).

PMID- 18821259
TI  - Indole carboxamides inhibit bovine testes hyaluronidase at pH 7.0 and indole
      acetamides activate the enzyme at pH 3.5 by different mechanisms.
AB  - Hyaluronidases are enzymes controlling many crucial physiological processes.
      Imbalanced enzymatic activity is connected with severe diseases. Because there is
      limited availability of drugs modulating hyaluronidase activity, the search for
      hyaluronidase interacting compounds is getting more and more important. A series
      of fifteen indole carboxamides and acetamides were synthesized and tested on
      inhibition of bovine testes hyaluronidase. In vitro assays were performed using
      stains-all at pH 7 and the Morgan-Elson reaction at pH 3.5. At neutral pH, the
      most active inhibitory compound was N-(Pyridin-4yl)-[5-bromo-1-(4
      fluorobenzyl)indole-3-yl]carboxamide (20) with an IC(50) value of 46 microM.
      Surprisingly, inhibition of all compounds was completely abolished by a decrease
      in pH. At pH 3.5 the activity of the enzyme was increased up to 134% by compound
      N-(4,6-Dimethylpyridin-2yl)-(1-ethylindole-3-yl)acetamide (24) at a concentration
      of 100 microM. The known activating effect of bovine serum albumine (BSA) on
      hyaluronidase activity was verified in the assay and compared to the effect of
      compound 24. Structure-activity relationships are discussed and a model is
      proposed, which explains the increase in activity at pH 3.5 by bonding of the
      protonated form of N-(4,6-Dimethylpyridin-2yl)-(1-ethylindole-3-yl)acetamide (24)
      to hyaluronic acid. The bonding results in an elongated form of the substrate
      with easier enzymatic access.

PMID- 18821260
TI  - N-Pyridinyl(methyl)-indole-1- or 3-propanamides and propenamides acting as
      topical and systemic inflammation inhibitors.
AB  - In this study, the synthetic way to new N-pyridinyl(methyl)indolylpropanamides
      acting as non acidic NSAIDs has been described. Pharmacomodulation was carried
      out at N(1) and C(5) of the indole ring and at the level of the propanamide
      chain. N(3)-pyridinylmethyl-[1(4-chlorobenzyl-5-chloroindol-3-yl)propanamide
      represents one of the most potent compounds in the TPA-induced mouse ear swelling
      assay, with a level of activity higher than that of ibuprofen and comparable to
      that of dexamethasone.

PMID- 18821261
TI  - Formulation and characterization of catalase in albumin microspheres.
AB  - Catalase in albumin microspheres were formulated for intravenous administration
      to antagonize the effects of over-production of reactive oxygenated species (ROS)
      such as hydrogen peroxide (H(2)O(2)) in septic shock. The aim was to increase
      effective half-life of catalase and take advantage of the phagocytic uptake of
      the encapsulated catalase by the vascular endothelium. Catalase microspheres were
      prepared by spray-drying. The microspheres were evaluated for particle size,
      particle shape and surface morphology by scanning electron microscopy (SEM), drug
      encapsulation efficiency, chemical stability, thermal stability and in vitro drug
      release characteristics. The microspheres had a mean particle size of 4.7 +/- 2
      microm, optimal for phagocytic uptake, as demonstrated by Makino et al. SEM
      revealed that microspheres were spherical with smooth surface morphology. An
      encapsulation efficiency of 91.5 +/- 3% was achieved and the encapsulated
      catalase was chemically and thermally stable. Application of in vitro drug
      release data to the Higuchi kinetic equation indicated matrix diffusion
      controlled catalase release from albumin microspheres.

PMID- 18821262
TI  - Real-time PCR quantification of Mycobacterium immunogenum in used metalworking
      fluids.
AB  - Rapid detection and quantification of Mycobacterium immunogenum in field samples
      of metalworking fluids (MWFs) is important for factory fluid surveillance
      programs. The applicability of the developed DNA extraction and quantitative real
      time PCR (qPCR) methods to detect and quantify M. immunogenum in used MWFs was
      evaluated. Total DNA from these samples was extracted, and M. immunogenum
      measured by qPCR by comparison with a standard curve derived from plasmid
      vectors. PCR counts were compared with bacterial culture counts. PCR counts of M.
      immunogenum varied from 1.42 x 10(3) to 3.68 x 10(6) cells/mL of MWFs. Recovery
      of M. immunogenum by bacterial culture varied from 2.5% to 70% of qPCR count in
      corresponding samples. Quantitative PCR could be used to measure M. immunogenum
      load in MWF samples with greater sensitivity and shorter processing time than the
      classic bacterial culture-based approach. The proposed qPCR approach could be
      routinely used in real-time PCR-equipped laboratories to provide early detection
      of M. immunogenum and to control proliferation that probably leads to
      hypersensitivity pneumonitis in exposed workers.

PMID- 18821263
TI  - On how death was handed back to families--bereavement.

PMID- 18821264
TI  - Maternal mortality due to psychiatric disorders in the Netherlands.

PMID- 18821265
TI  - Comparison of labor course and women's sexuality in planned and unplanned
      pregnancy.
AB  - OBJECTIVE: This study compares several parameters of sexual life and course of
      labor in women with planned and unplanned pregnancy. METHODS: 339 primiparas
      participated in our study; they filled in a questionnaire concerning their sexual
      life during pregnancy on the second or third day after the delivery. One question
      also stressed planning of pregnancy. 246 women (i.e., 72.6%) indicated planned
      pregnancy, 93 pregnancies (i.e., 27.4%) were not planned. RESULTS: Significant
      decrease of coital activity and number of orgasms and increase of sexual
      dysfunctions were observed in the whole study group during pregnancy. Significant
      differences between women with planned and unplanned pregnancy were observed only
      in frequency of vaginal dryness and pelvic pain. CONCLUSIONS: According to the
      results of this study, unplanned pregnancy has no adverse effect on parameters of
      the labor. The equal rate of partner's presence at delivery shows a high
      involvement of the partners of unmarried women.

PMID- 18821266
TI  - Gynaecological symptoms associated with physical and sexual violence.
AB  - OBJECTIVE: The study aims to describe the prevalence of violent physical and
      sexual experiences in female outpatients and to identify specific gynaecological
      symptoms that are associated with a history of abuse. STUDY DESIGN: We performed
      a cross-sectional study among native German women. The confidential self
      administered questionnaire included items on physical and sexual abuse and on the
      patient's medical history. Of a total of 1941 eligible women, 730 (37.6%)
      participated in the survey. We calculated prevalence rates of physical and sexual
      abuse and compared victims and non-victims of violence with respect to specific
      symptoms and complaints. We developed multivariate models for pelvic pain and
      vaginal infection. RESULTS: The lifetime prevalence of severe physical violence
      by any kind of perpetrator was 35.5%. 13.5% of participants reported a completed
      rape. The lifetime prevalence of physical and/or sexual intimate partner violence
      (IPV) was 28.3%. Physical and sexual abuse is significantly associated with
      irregular menstrual cycle, urinary tract infections and pelvic pain independent
      of menses. CONCLUSIONS: Physical and sexual violence are associated with many
      gynecological symptoms. Especially gynecologists and general practitioners have
      to be aware that their patients might be victims of violence. This is important
      for adequate diagnosis and therapy and to avoid retraumatization in affected
      women.

PMID- 18821267
TI  - Influence of recovery intensity on time spent at maximal oxygen uptake during an
      intermittent session in young, endurance-trained athletes.
AB  - In this study, we examined the effects of three recovery intensities on time
      spent at a high percentage of maximal oxygen uptake (t90[Vdot]O(2max)) during a
      short intermittent session. Eight endurance-trained male adolescents (16 +/- 1
      years) performed four field tests until exhaustion: a graded test to determine
      maximal oxygen uptake ([Vdot]O(2max); 57.4 +/- 6.1 ml x min(-1) . kg(-1)) and
      maximal aerobic velocity (17.9 +/- 0.4 km x h(-1)), and three intermittent
      exercises consisting of repeat 30-s runs at 105% of maximal aerobic velocity
      alternating with 30 s active recovery at 50% (IE(50)), 67% (IE(67)), and 84%
      (IE(84)) of maximal aerobic velocity. In absolute values, mean t90[Vdot]O(2max)
      was not significantly different between IE(50) and IE(67), but both values were
      significantly longer compared with IE(84). When expressed in relative values (as
      a percentage of time to exhaustion), mean t90[Vdot]O(2max) was significantly
      higher during IE(67) than during IE(50). Our results show that both 50% and 67%
      of maximal aerobic velocity of active recovery induced extensive solicitation of
      the cardiorespiratory system. Our results suggest that the choice of recovery
      intensity depends on the exercise objective.

PMID- 18821268
TI  - Retrieval opportunities while multitasking improve name recall.
AB  - In two experiments we tested whether providing retrieval opportunities while
      people were multitasking would improve memory for names. College students (n=195)
      in Experiment 1 did addition problems and intermittently were "introduced" to 12
      face-name pairs to learn. For half the names students were given three within
      list retrieval opportunities. Name recall (cued with the faces) was tested either
      immediately or after 24 hours. Retrieval opportunities improved name recall with
      both immediate and delayed tests. Experiment 2 more closely resembled the
      multitasking required in a real-life social situation. College students (n=98)
      viewed a videotape and were asked to learn the names of 12 dormitory residents
      who were introduced during an ongoing conversation. Retrieval opportunities were
      provided for 8 of the 12 residents by having them appear three additional times
      in the video without repeating their names. Retrieval opportunities improved name
      recall, but the effect was much smaller than in Experiment 1. The present
      research demonstrates that distributed retrieval can be effective when people are
      multitasking including when the multitasking involves a conversation.

PMID- 18821269
TI  - Pathological gambling, delusional parasitosis and adipsia as a post-haemorrhagic
      syndrome: a case report.
AB  - The authors describe the case of a 70-year-old male who developed a peculiar
      syndrome characterized by pathological gambling (PG), delusional parasitosis and
      adipsia with mild frontal symptoms. Onset of the syndrome followed a cerebral
      haematoma involving hypothalamic and bilateral ventromedial prefrontal areas. The
      potential manifestation of PG following a lesion in the above areas may
      contribute towards furthering the understanding of pathological conditions
      underlying this disorder.

PMID- 18821270
TI  - Formulation and evaluation of curcumin gel for topical application.
AB  - The aim of the present investigation was to develop and study topical gel
      delivery of curcumin for its anti-inflammatory effects. Carbopol 934P (CRB) and
      hydroxypropylcellulose (HPC) were used for the preparation of gels. The
      penetration enhancing effect of menthol (0-12.5% w/w) on the percutaneous flux of
      curcumin through the excised rat epidermis from 2% w/w CRB and HPC gel system was
      investigated. All the prepared gel formulations were evaluated for various
      properties such as compatibility, drug content, viscosity, in vitro skin
      permeation, and anti-inflammatory effect. The drug and polymers compatibility was
      confirmed by Differential scanning calorimetry and infrared spectroscopy. The
      percutaneous flux and enhancement ratio of curcumin across rat epidermis was
      enhanced markedly by the addition of menthol to both types of gel formulations.
      Both types of developed topical gel formulations were free of skin irritation. In
      anti-inflammatory studies done by carrageenan induced rat paw oedema method in
      wistar albino rats, anti-inflammatory effect of CRB, HPC and standard gel
      formulations were significantly different from control group (P < 0.05) whereas
      this effect was not significantly different for CRB and HPC gels formulations to
      that of standard (diclofenac gel) formulation (P > 0.05). CRB gel showed better %
      inhibition of inflammation as compared to HPC gel.

PMID- 18821271
TI  - Effect of freeze-dryer design on drying rate of an amorphous protein-formulation
      determined with a gravimetric technique.
AB  - A freeze-drying balance was used to determine momentary drying-rate, m(t), of a
      sucrose/BSA formulation contained in a vial with varying shelf packing density,
      O2. A comparison between two different laboratory-scale freeze-dryers was made.
      The effects of O2 on m(t) differed between the two units, attributed to drying
      chamber design and its effects on heat transfer. At high O2 the differences are
      annulled because of the shielding effects of surrounding vials. Parallel effects
      of O2 were also found on product temperature, Tb, measured in the balance vial.
      Tb was used to calculate vial heat transfer coefficient, Kv. Kv was strongly
      reduced with increasing O2, but reached a plateau value at high O2.

PMID- 18821272
TI  - Sustained delivery of intact drug to the colon: mesalamine formulation and
      temporal gastrointestinal transit analysis.
AB  - The goal was to use temporal gastrointestinal transit simulations and formulation
      to predict and provide sustained input of target-site directed oral drug delivery
      exclusively into the colon. Using mesalamine as the model drug for formulation
      coupled with stomach emptying rates (fed and unfed) plus intestinal transit times
      demonstrates concepts and provides a specific example for treatment in ulcerative
      colitis. Formulation involved extrusion and spheronization into beads which were
      then coated with aqueous Eudragit S. Drug is released only at colonic pH and
      gastrointestinal transit predicts sustained drug input into the colon, especially
      when food effects are included.

PMID- 18821273
TI  - Update on endoscopic ultrasound: how much for imaging, needling, or therapy?

PMID- 18821274
TI  - Oral and i.v.-to-p.o. switch antibiotic therapy of hospitalized patients with
      serious infections.

PMID- 18821275
TI  - Degenerative and traumatic changes in the lower cervical spine facet joints.
AB  - OBJECTIVE: The aim of this study was to examine anatomical variables of the lower
      cervical spine facet joints with regard to age, gender, and exposure to trauma.
      METHODS: The lower four cervical spine segments (C4-C7 included) were obtained
      from 40 subjects during autopsy: 12 females and 28 males (median age 35 years,
      range 20-49). Through an available 636 unique facets (318 joints), 1830 randomly
      obtained observation lines were defined. Each of these lines resembled a 3-mm
      thick parasaggital slice through a facet from which 10-microm-thick histological
      sections were produced and evaluated microscopically. Inter- and intraobserver
      agreement was tested on four randomly selected facets from each subject. RESULTS:
      Significant age-, gender-, and trauma-related changes in the bone, cartilage, and
      soft tissues were observed, including subchondral sclerosis, fibrillation and
      splitting of cartilage, and cartilage length differences. Females were less
      affected by changes in the cartilage than males. Two synovial folds were present
      in all but one joint. Moderate interobserver and good intraobserver agreement
      were achieved. CONCLUSIONS: This study provides knowledge of the anatomy of the
      cervical spine facet joints. The findings support existing knowledge that males
      are more commonly affected by degenerative changes than females and that these
      changes are common from a young age. Histomorphometry confirms the presence of
      synovial folds in all of the facet joints. Following spinal trauma, pathological
      lesions may be produced in the facet joints and/or accentuate already existing
      pathology. The information provided in this study may have relevance for patients
      with neck pain.

PMID- 18821276
TI  - Paediatric contracturing granulomatous myositis.

PMID- 18821277
TI  - Can sonography be used to predict the response to intra-articular corticosteroid
      injection in primary osteoarthritis of the knee?

PMID- 18821278
TI  - Efficacy of adalimumab, etanercept, and infliximab in psoriatic arthritis based
      on ACR50 response after 24 weeks of treatment.

PMID- 18821281
TI  - Side distinct sciatic nerve recovery differences between rats and mice.
AB  - The Sciatic Functional Index (SFI) is widely used to evaluate functional recovery
      after sciatic nerve injury, primarily in the rat, and more recently shown useful
      in the mouse. This quantitative, non-invasive method allows tracking of
      regeneration capability, visible in the gait of the animal. Using a Martin micro
      needle holder, carrying a force measured to be 49.2 N, the left sciatic nerve was
      crushed for 60 s. We accumulated data from walking tracks collected
      preoperatively and 1, 7, 14, 21, and 28 days after injury. SFI values were first
      calculated in the traditional manner. Then using the preoperative values as the
      normal value in the postoperative calculations, SFI was again calculated; this
      isolated the calculations to either injured or contra lateral leg giving a
      "split" plot. The traditional SFI calculations resulted in typical shaped graphs
      for both rats and mice. However, the "split" SFI calculations showed how rats and
      mice differ in their recovery from sciatic nerve injury. The mouse graph shows
      the intact leg remaining stable and the injured leg having functional impairment,
      which then recovers. The rat graph showed functional impairment of the injured
      leg, however, the intact leg had an increase in SFI values as if to compensate
      until the injured leg showed recovery.

PMID- 18821280
TI  - Multiple parietal operculum subdivisions in humans: tactile activation maps.
AB  - We focused the present analysis on blood-oxygen-level-dependent responses evoked
      in four architectonic subdivisions of human posterior parietal operculum (PO)
      during two groups of tasks involving either vibrotactile stimulation or rubbing
      different surfaces against the right index finger pad. Activity localized in
      previously defined parietal opercular subdivisions, OP 1-4, was co-registered to
      a standard cortical surface-based atlas. Four vibrotactile stimulation tasks
      involved attention to the parameters of paired vibrations: (1) detect rare target
      trials when vibration frequencies matched; (2) select the presentation order of
      the vibration with a higher frequency or (3) longer duration; and (4) divide
      attention between frequency and duration before selecting stimulus order. Surface
      stimulation tasks involved various discriminations of different surfaces: (1)
      smooth surfaces required no discrimination; (2) paired horizontal gratings
      required determination of the direction of roughness change; (3) paired shapes
      entailed identifying matched and unmatched shapes; (4) raised letters involved
      letter recognition. The results showed activity in multiple somatosensory
      subdivisions bilaterally in human PO that are plausibly homologues of
      somatosensory areas previously described in animals. All tasks activated OP 1,
      but in vibrotactile tasks foci were more restricted compared to moving surface
      tasks. Greater spatial extents of activity especially in OP 1 and 4 when surfaces
      rubbed the finger pad did not support previously reported somatotopy of the
      second finger representation in "S2". The varied activity distributions across OP
      subdivisions may reflect low-level perceptual and/or cognitive processing
      differences between tasks.

PMID- 18821282
TI  - Topography and chemoarchitecture of the striatum and pallidum in a monotreme, the
      short-beaked echidna (Tachyglossus aculeatus).
AB  - The topography and chemoarchitecture of the striatum and pallidum in a monotreme,
      the short-beaked echidna (Tachyglossus aculeatus) have been studied using Nissl
      staining in conjunction with myelin staining, enzyme reactivity to
      acetylcholinesterase and NADPH diaphorase, and immunoreactivity to parvalbumin,
      calbindin, calretinin, tyrosine hydroxylase, neuropeptide Y, and neurofilament
      protein (SMI-32 antibody). All those components of the striatum and pallidum
      found in eutherian mammals could also be identified in the echidna's brain, with
      broad chemoarchitectural similarities to those regions in eutherian brains also
      apparent. There was a clear chemoarchitectural gradient visible with parvalbumin
      immunoreactivity of neurons and fibers, suggesting a subdivision of the echidna
      caudatoputamen into weakly reactive rostrodorsomedial and strongly reactive
      caudoventrolateral components. This may, in turn, relate to subdivision into
      associative versus sensorimotor CPu and reflect homology to the caudate and
      putamen of primates. Moreover, the chemoarchitecture of the echidna striatum
      suggested the presence of striosome-matrix architecture. The morphology of
      identified neuronal groups (i.e., parvalbumin, calbindin, and neuropeptide Y
      immunoreactive) in the echidna striatum and pallidum showed many similarities to
      those seen in eutherians, although the pattern of distribution of calbindin
      immunoreactive neurons was more uniform in the caudatoputamen of the echidna than
      in therians. These observations indicate that the same broad features of striatal
      and pallidal organization apply across all mammals and suggest that these common
      features may have arisen before the divergence of the monotreme and therian
      lineages.

PMID- 18821283
TI  - Podokinetic after-rotation in a simulated reduced gravity environment.
AB  - Stepping in place on a rotating platform for a period of 15 minutes induces an
      adaptive response, podokinetic after-rotation (PKAR), which causes a blindfolded
      individual to inadvertently rotate when attempting to step in place on the floor.
      The purpose of this investigation was to determine whether lower extremity load
      receptors were involved in this adaptation. As load receptor input is critical
      for locomotion, we hypothesized that manipulating load via body weight support
      (BWS) would influence PKAR. Eleven healthy female volunteers performed 15 minutes
      of stepping in place on a rotating treadmill (stimulation), followed by 10
      minutes of stepping in place (response) without vision on a stationary surface.
      Response and stimulation periods were with 50% body weight support (BWS) and
      without body weight support (NoBWS) in all four possible combinations (BWS-BWS,
      NoBWS-NoBWS, BWS-NoBWS, and NoBWS-BWS). Conditions were randomly assigned to all
      subjects and performed on four separate occasions at least 48 hr apart. During
      the 10-min PKAR response period, trunk angular velocity was calculated and
      plotted versus time, and exponential models were applied to the data to obtain
      curve-fit parameters for each condition. Despite the manipulations of BWS, no
      significant differences were found for any parameter value (p = 0.13-0.98). BWS
      applied during stimulation only, response only, or during both stimulation and
      response does not appear to influence PKAR. This suggests that load receptors may
      not play a critical role in mediating adaptive changes in locomotor trajectory
      control in response to walking on a rotating surface.

PMID- 18821284
TI  - Mesenteric and tactile Pacinian corpuscles are anatomically and physiologically
      comparable.
AB  - Pacinian corpuscles (PCs) in cat mesentery have been studied extensively to help
      determine the structural and functional bases of tactile mechanotransduction.
      Although we, like many other investigators, have found that the mesenteric
      receptors are anatomically very similar to those found in mammalian skin, few
      physiological characteristics of the mesenteric PCs and those of the skin have
      been compared. Action-potential rate-amplitude and frequency characteristics (10
      Hz-1 KHz), as well as interval (IH) and peri-stimulus-time (PSTH) histograms in
      response to sinusoidal displacements were obtained from nerve fibers innervating
      mesenteric PCs and from PC fibers innervating cat glabrous skin. The intensity
      characteristics obtained on both preparations showed similar response profiles,
      including equal slopes for low stimulus intensities (approximately 10, with
      impulse ratios/20 dB displacement) and one and two impulse/cycle entrainment. The
      frequency characteristics of both groups were U-shaped with similar low-frequency
      slopes (-12.5 dB/octave) and bandwidths (Q(3dB) = 1.4). The best frequency for
      both the tactile PCs' and mesenteric PCs was 250 Hz, which is in the expected
      range. The IHs showed entrainment and the PSTHs showed neither transient
      responses nor adaptation to steady-state sinusoidal stimuli. The functional
      similarity between mesenteric PCs' nerve responses and those of tactile PC
      afferents, as well as the receptors' anatomical similarity, lead us to suggest
      that the mesenteric PC can act as a model for those in the skin. Furthermore,
      since the frequency characteristics of the two PC types are similar, it is
      concluded that the skin, while attenuating stimulus intensity, does not impart
      temporal filtering of vibratory stimuli.

PMID- 18821286
TI  - Hypogonadotrophic hypogonadism in type 2 diabetes.
AB  - Recent work shows a high prevalence of low testosterone and inappropriately low
      luteinizing hormone (LH) and follicle stimulating hormone (FSH) concentrations in
      type 2 diabetes. This syndrome of hypogonadotrophic hypogonadism (HH) is
      associated with obesity in patients with type 2 diabetes. However, the duration
      of diabetes or HbA1c are not related to HH. Furthermore, recent data show that HH
      is not associated with type 1 diabetes. C-reactive protein concentrations have
      been shown to be elevated in patients with HH and are inversely related to plasma
      testosterone concentrations. This inverse relationship between plasma free
      testosterone and C- reactive protein concentrations in patients with type 2
      diabetes suggests that inflammation may play an important role in the
      pathogenesis of this syndrome. This is of interest since inflammatory mechanisms
      may have a cardinal role in the pathogenesis of insulin resistance. It is also
      relevant that in the mouse, deletion of the insulin receptor in neurons leads to
      HH in addition to a state of systemic insulin resistance. It has also been shown
      that insulin facilitates the secretion of gonadotrophin releasing hormone (GnRH)
      from neuronal cell cultures. Thus, HH may be the result of insulin resistance at
      the level of the GnRH secreting neuron. Low testosterone concentrations are also
      related to an increase in total and regional adiposity. This review discusses
      these issues and attempts to make the syndrome relevant as a clinical entity.
      Clinical trials are required to determine whether testosterone replacement
      alleviates insulin resistance and inflammation. In addition, low testosterone
      levels are associated with an increase in cardiovascular events. Testosterone
      therapy may therefore, reduce cardiovascular risk. This important aspect requires
      further investigation.

PMID- 18821287
TI  - Anabolic-androgenic steroid effects on early morbid symptoms after open
      prostatectomy: a pilot study.
AB  - OBJECTIVES: Anabolic-androgenic steroids such as Nandrolone phenpropionate (NP)
      dramatically improve the tolerance to acute stress conditions, strength, and
      subsequently the quality of life in elderly men. We hypothesize that preoperative
      pulse-dose supraphysiological NP administration might improve the early morbid
      symptoms in older patients undergoing open prostatectomy. METHODS: From 2005 to
      2006, 54 patients with a mean age of 70 years, diagnosed as benign prostatic
      hyperplasia and hospitalized for open prostatectomy were enrolled in the study.
      They were randomly selected to receive preoperative supraphysiological NP (100
      mg, intramuscularly, pulse-dose) or sesame oil placebo, prospectively. Early
      postoperative morbid symptoms including subjective urinary symptoms (dysuria,
      bladder retention sensation), incision site pain and general satisfaction of
      their current urinary condition were assessed by a 6-point scale, self
      administrated questionnaire at 24 and 48 h, postoperatively. The sex hormone
      binding globulin and the testosterone levels were also measured. RESULTS: The 24
      h postoperative symptoms were significantly reduced in the NP group compared to
      the placebo (6.18 +/- 2.81 versus 9.77 +/- 2.15; P < 0.001). The postoperative
      symptoms were reported to have a decline in the 48 h following operation, though
      was calculated to be statistically insignificant (4.48 +/- 2.32 versus 5.55 +/-
      1.84; P = 0.06). There was no complication attributed to NP therapy. CONCLUSIONS:
      The data supported the hypothesis that the preoperative anabolic steroid
      supplements (such as NP) could result in a better postoperative endurance in
      elderly men undergoing open prostatectomy. Further studies, longer and repeated
      pulse injections in a larger number of older men are mandatory to prove the
      claim.

PMID- 18821288
TI  - Increased prevalence of erectile dysfunction (ED): results of the second
      epidemiological study on sexual activity and prevalence of ED in Thai males.
AB  - OBJECTIVE: The aim of this study is to investigate changes in sexual activity and
      the prevalence of erectile dysfunction (ED) in Thai males. In addition, the
      treatment-seeking behaviour of Thai patients suffering from ED is also
      investigated. MATERIALS AND METHODS: In a cross sectional study using a
      standardized questionnaire with a multi-stage stratified random sampling, 2,269
      men aged 40-70 were interviewed. The questionnaire was designed to investigate
      the effects of socioeconomic factors, medical conditions and unhealthy lifestyles
      on the development of ED. Furthermore, the questionnaire was designed to
      characterize the treatment-seeking behaviour of Thai patients suffering from ED.
      RESULTS: Compared to the first report dated the year 2000, the prevalence of ED
      has increased from 37.5% to 42.18%. In terms of socioeconomic factors, the
      highest prevalence of ED was observed among unemployed men (78.51%). Prostatism
      and/or prostatitis (Odd ratios (OR) = 2.02) and long histories of smoking (more
      than 30 years, OR = 2.36) were identified as statistically significant risk
      factors for ED, with p-values of <0.001. It is important to notice that 38.78% of
      the ED patients wanted to discuss their problem with spouses or partners. Three
      quarters of the ED patients (74.54%) preferred oral medication as therapy.
      CONCLUSIONS: The epidemiology of ED in Thailand is changing. An increased
      prevalence of ED does require further epidemiological studies on a regular basis
      in order to better understand the etiology of ED and look for measures (such as
      education) to counter the disease.

PMID- 18821289
TI  - Relationship between vitamin D receptor BsmI and FokI polymorphisms and
      anthropometric and biochemical parameters describing metabolic syndrome.
AB  - INTRODUCTION: It was found that vitamin D may have a direct effect on adipocyte
      differentiation and metabolism and might be involved in the glucose regulation of
      insulin secretion, as suggested from the discovery of a nuclear localization of
      1,25-(OH)(2)D(3) in pancreatic islets. In recent years, several polymorphisms in
      the VDR gene which are able to alter the activity of VDR protein have been
      described. The BsmI and FokI polymorphisms were described in relation to obesity
      and type 2 diabetes. The aim of the study was to find whether there are
      associations between BsmI and FokI polymorphisms and anthropometric (BMI, WHR,
      BP) and biochemical parameters describing metabolic syndrome. MATERIALS AND
      METHODS: Studied were 176 randomly selected men aged 25-65 years (mean: 51.99
      years) with a mean BMI of 28.06 kg/m(2). Two polymorphisms of the VDR gene (FokI
      and BsmI) were explored using the PCR-RFLP method. Serum glucose, insulin, total
      cholesterol, LDL, HDL, and TG were measured using commercially available kits.
      RESULTS: It was found that BB carriers tend to have higher BMI (29.00 +/- 3.74
      versus 26.81 +/- 3.76, p = 0.024) and waist circumference (101.79 +/- 10.59
      versus 96.23 +/- 10.35, p = 0.014) compared with the bb genotypes. Similarly, FF
      and Ff carriers had higher fasting insulin levels than the ff genotypes (12.30 +/
      10.26 versus 9.76 +/- 5.88, p = 0.001 and 9.76 +/- 5.88 vs. 6.35 +/- 2.64, p =
      0.008), and lover cHDL levels in comparison to ff genotypes (52.28 +/- 10.02
      versus 60.63 +/- 16.58, p = 0.015 and 53.70 +/- 12.03 versus 60.63 +/- 16.58, p =
      0.032. Besides these, no significant differences were found. CONCLUSIONS: The
      BsmI VDR polymorphism seems to influence BMI, while the FokI VDR polymorphism
      appears to affect insulin sensitivity and serum cHDL level.

PMID- 18821290
TI  - Effect of testosterone therapy on lumbar spine and hip mineral density in elderly
      men.
AB  - OBJECTIVE: The aim of the present study was to analyse the effect of testosterone
      therapy on bone mineral density in healthy elderly men who had low levels of
      total testosterone. DESIGN: Randomized, double-blind, placebo-controlled study.
      PARTICIPANTS: Forty-eight men over 60 years old with decreased testosterone
      levels (< or =320 ng/dL) comprised the study. Twenty-five out of 48 received
      intramuscular injections of testosterone enanthate every three weeks during 12
      months; the remaining 23 participants formed the control group. All participants
      had measurements of bone mineral density (BMD) in both lumbar spine and hip
      before and at the end of the study as well as testosterone and 17-beta estradiol
      levels. RESULTS: Testosterone treated group exhibited a significant (p < 0.05)
      increment (from 1.198 +/- 0.153 to 1.240 +/- 0.141 g/cm(2)) in lumbar BMD in
      parallel with a significant (p < 0.001) increment (from 301 +/- 32 to 471 +/- 107
      ng/dL) in testosterone concentrations, whereas no significant change occurred in
      femoral neck BMD. CONCLUSIONS: Testosterone therapy elicited a positive effect
      only in lumbar BMD in elderly men with diminished testosterone serum levels.

PMID- 18821291
TI  - The effect of testosterone therapy on lower urinary tract symptoms/bladder and
      sexual functions in men with symptomatic late-onset hypogonadism.
AB  - OBJECTIVE: To prospectively investigate the effect of testosterone therapy on
      lower urinary tract symptoms (LUTS)/bladder and sexual functions in men with
      symptomatic late-onset hypogonadism (SLOH). METHODS: The study included 25 men
      (age range 38 to 73 years) presented with sexual dysfunction, having SLOH, at a
      single university hospital. All men received testosterone replacement therapy
      with transdermal testosterone 50-100 mg gel per day for one year. Urodynamic
      studies with pressure-flow analysis, measurement of prostate volume, prostate
      specific antigen (PSA) and free PSA level, International Prostate Symptom Score
      (IPSS), Aging Male Symptom (AMS) scale and International Index of Erectile
      Function (IIEF-5) score were recorded in all men before and after one year of the
      treatment. RESULTS: The mean AMS score significantly decreased from 40.4 +/- 7.3
      to 28.8 +/- 5.31 (p = 0.001), and mean IIEF-5 score significantly increased from
      8.84 +/- 3.76 to 14.36 +/- 3.62 (p = 0.001). The mean maximal bladder capacity
      and compliance significantly increased (p = 0.007 and p = 0.032, respectively),
      and mean detrusor pressure at Qmax significantly decreased from pre-treatment to
      post-treatment (p = 0.017). CONCLUSION: This study suggests that in addition to
      improvement in sexual functions, testosterone therapy may also improve
      LUTS/bladder functions by increasing bladder capacity and compliance and
      decreasing detrusor pressure at maximal flow in men with SLOH.

PMID- 18821292
TI  - Preliminary study of proteomic shift from normal to premalignant laryngeal
      lesions and to laryngeal squamous cell carcinoma.
AB  - CONCLUSIONS: The malignant shift was discovered to begin even in the premalignant
      stage in the comparison of premalignant laryngeal lesions (PMLLs) with laryngeal
      squamous cell carcinoma (LSCC) and healthy controls. The differential expression
      of proteins among normal, PMLL, and cancer cells might provide the prediction for
      the changes from normal to PMLL and to malignant disease. OBJECTIVES: To study
      the serum proteomic shift from normal control to PMLL and progression to LSCC.
      MATERIALS AND METHODS: A total of 211 serum samples from patients with LSCC (n =
      89 at stage I-II) or PMLL (n = 57), or normal controls (n = 65) were obtained
      with informed consent. Serum protein profiles on weak cationic exchange (WCX2)
      were performed by surface-enhanced laser desorption/ionization mass spectrometry
      (SELDI-TOF MS) and then analyzed by Biomarker Wizard software. RESULTS: Peak
      intensities of serum from PMLLs were compared to normal controls and serum from
      patients with LSCC. Mean intensity differed significantly only for one peak (4532
      Da, p = 0.032) between LSCC and precancerous diseases, while 13 peaks differed
      significantly between precancerous diseases and normal controls. Eighteen
      biomarkers were selected to separate stage I- II LSCC patients and healthy
      controls.

PMID- 18821293
TI  - Abstracts of the 19th International Symposium on ALS/MND. November 3-5, 2008.
      Birmingham, United Kingdom.

PMID- 18821323
TI  - 50 years of the Society for the study of Human Biology.

PMID- 18821324
TI  - Downward percentile crossing as an indicator of an adverse prenatal environment.
AB  - BACKGROUND: Postnatal health sequelae of low birth weight have been attributed to
      'poor fetal growth' from inferred adverse prenatal environments; risks augmented
      by infant growth rates. Identifying prenatal growth-restricting events is
      essential to clarify pathways and mechanisms of fetal growth. AIM: The specific
      aim of this investigation was to examine whether an episode of preterm labor may
      compromise fetal growth. SUBJECTS AND METHODS: Fetal size at the end of the
      second trimester and birth were compared among women with uncomplicated
      pregnancies (n = 3167) and those who experienced an episode of preterm labor (<37
      weeks) and subsequently delivered at term (> or =37 weeks, n = 147). Fetal weight
      estimated from ultrasound measures, and changes in weight standard scores across
      the third trimester investigated significant centile crossing (>0.67 standard
      deviation score change). RESULTS: Fetuses delivered at term after an episode of
      preterm labor were smaller at birth relative to their peers than at the end of
      the second trimester, and were 47% more likely to experience clinically
      significant downward centile crossing (p < 0.05) than their peers (OR 1.47, 95%
      CI 1.04-2.07). CONCLUSION: An episode of preterm labor may signal an adverse
      prenatal environment for term-delivered neonates. Epidemiologically silent events
      in the natural history of pregnancy are an understudied source of fetal growth
      compromise as inferred by small birth size among peers.

PMID- 18821325
TI  - Secular change in the growth status of urban and rural schoolchildren aged 6-13
      years in Oaxaca, southern Mexico.
AB  - BACKGROUND: Populations in the state of Oaxaca in southern Mexico are at high
      risk for malnutrition and marginalization. AIM: The study compared secular
      changes in the growth status of urban and rural schoolchildren in the Valley of
      Oaxaca between the 1970s and 2000. SUBJECTS AND METHODS: Cross-sectional surveys
      of boys and girls aged 6-13 years (n = 1472) were carried out in an urban colonia
      populares in 1972 and 2000 and a rural indigenous community in 1978 and 2000.
      Height, sitting height and weight were measured; leg length, sitting height
      ratio, BMI, and prevalence of stunting, underweight, overweight and obesity were
      calculated. Sex-specific ANCOVA controlling for age was used. RESULTS: Both urban
      and rural children experienced significant secular gains in linear dimensions,
      body weight and the BMI between the 1970s and 2000. Estimated rates of secular
      gain overlapped considerably between urban and rural children. Secular gains in
      the BMI are significantly greater in urban than rural boys and girls. Urban-rural
      differences in linear dimensions and body weight in 2000 compared to the 1970s do
      not differ in either sex, but urban-rural differences in the BMI are greater in
      boys and girls in 2000 compared to the 1970s. The prevalence of stunting declined
      while that of overweight and obesity increased. CONCLUSIONS: Significant secular
      increases in body size occurred between the 1970s and 2000, but there was
      considerable overlap between urban and rural children. Only secular gains in the
      BMI were significantly greater in urban than rural boys and girls and the
      magnitudes of urban-rural differences in the BMI were greater in 2000 than in the
      1970s.

PMID- 18821326
TI  - Risk genotypes and haplotypes of the GLUT1 gene for type 2 diabetic nephropathy
      in the Tunisian population.
AB  - OBJECTIVE: Diabetic nephropathy (DN) is a long-term complication of both type 1
      and type 2 diabetes. Genetic studies on DN have been of little help so far, since
      several genetic association studies have shown conflicting results. Here we
      report the findings of a case-control study on five SNPs in the glucose
      transporter 1 (GLUT1) gene. The study investigated the association of five GLUT1
      genotypes and haplotypes with DN. RESEARCH DESIGN AND METHODS: All subjects, 126
      DN (cases) and 273 type 2 diabetes (controls), were genotyped using the
      polymerase chain reaction restriction fragment length polymorphism. RESULTS: The
      TT and the AA genotypes of the Haell and Enh2 SNP1, increased the risk of DN. The
      study also identified CGT as the highest risk haplotype (4.4-fold) followed by
      CAT with an increased risk of DN of 2.6-fold. CONCLUSIONS: The GLUT1 gene confers
      susceptibility to DN in type 2 diabetes patients in the Tunisian population.

PMID- 18821327
TI  - Diversified genomic contribution among south Indian populations--a study on four
      endogamous groups of Andhra Pradesh.
AB  - BACKGROUND: The present study examines genomic variation among three tribal
      (Nayakpod, Thoti and Kolam) and a caste (Niyogi Brahmin) population groups of
      Andhra Pradesh, south India. AIM: The present study examined the genomic
      diversity of the populations in relation to other population groups of India
      using 20 autosomal loci. SUBJECTS AND METHODS: A total of 204 blood samples from
      the population groups described above were collected and analysis was carried out
      following standard protocols. RESULTS: All markers were found to be polymorphic
      in these groups except AluCD4 among Thotis. High average heterozygosity values
      (0.3927 among Thotis to 0.4268 among Brahmins) are comparable with the available
      autosomal (Alu and restriction site polymorphisms) data for the Nilgiri hill
      tribes of Tamil Nadu, south India. The gene differentiation value (Gst) was found
      to be 4.2. The principal coordinate analysis (PCO) based on data from the 20
      markers presents a smaller cluster of presently studied populations than that of
      the Nilgiri hill tribes of Tamil Nadu, south India. CONCLUSION: Although the
      presently studied populations of Andhra Pradesh have heterozygosity similar to
      that of Nilgiri hill populations, the former are more closely placed on the PCO
      plot than the latter, who are more scattered. Also the gene differentiation (Gst)
      of the former is much lower than that of the latter, indicating considerable
      regional variation in the inflow of genes from diverse ethnic groups within south
      India.

PMID- 18821328
TI  - Early stature prediction method using stature growth parameters.
AB  - BACKGROUND: The creation of an accurate growth prediction method for human
      stature at a stage of growth has been an interesting challenge in medical science
      and human biology. AIM: The aim of this study was to develop a non-radiographic
      final stature prediction method that is applicable in the early pubertal growth
      period. SUBJECTS AND METHODS: Randomly selected 12-year serial stature growth
      data for 400 Koreans were fitted with two nonlinear growth curves: Preece and
      Baines model 1 (PB1) and Jolicoeur-Pontier-Pernin-Sempe (JPPS) functions. Five
      biological parameters, including take-off (TO) related parameters, were derived
      by differentiation of the two curves, respectively. Those five variables were
      composed into a multiple linear regression equation for final stature prediction.
      In the cross-validation subjects, TO-related variables were estimated by linear
      interpolation from the partial growth data prior to estimation age, then
      incorporated into the prediction equation. RESULTS: The final stature prediction
      model had excellent validity and accuracy when applied to the cross-validation
      samples. Prediction accuracy increased according to increasing years after take
      off. CONCLUSIONS: This study suggests that a final stature prediction method
      using multiple regression analysis that includes biological parameters can
      predict stature growth with sufficient validity and accuracy. Incorporation of TO
      related parameters allowed us to develop earlier growth evaluation and prediction
      methods compared with other previous methods.

PMID- 18821329
TI  - Childhood circumstances and anthropometry: the Boyd Orr cohort.
AB  - BACKGROUND: Childhood environment is known to affect stature in childhood and
      adulthood. Peak growth for different anthropometric measures occurs at different
      times and so associations with childhood conditions that vary across different
      components of stature may indicate periods of growth that are particularly
      influenced by environmental factors. METHODS: The study examined relationships
      between anthropometric measurements (foot length, shoulder breadth, height, trunk
      and leg length) and childhood exposures (breast-feeding, birth order, household
      income, household food expenditure, social class, crowding, number of children in
      the household, and household diet) in 2376 members of the Boyd Orr cohort aged 2
      14 years. RESULTS: All childhood exposures were associated with childhood
      anthropometric measures to some degree. In multivariable models, the most
      consistent relationships were positive associations of anthropometric measures
      with ever being breast-fed, decreasing number of children in the household and,
      in boys, increasing household income. There was a steadily decreasing gradient in
      the strength of associations across different anthropometric measures; the
      strongest were observed with height followed by leg length, foot length, trunk
      and shoulder breadth. CONCLUSIONS: The individual components of stature most
      strongly associated with childhood environment in this age group were leg and
      foot length.

PMID- 18821330
TI  - Anthropometric and bone-related biochemical factors are associated with different
      haplotypes of ANKH locus.
AB  - BACKGROUND: The human homologue of the mouse progressive ankylosis (ANKH) gene is
      one of the key genetic factors involved in bone mineralization. Previous studies
      have shown that plasma levels of osteoprotegerin (OPG) and parathyroid hormone
      (PTH) are associated with the distal region of the ANKH gene, whereas skeletal
      size measurements are associated with the promoter region. AIM: The present study
      examines the possible phenotype-haplotype specificity of the associations in
      these two gene regions. SUBJECTS AND METHODS: The total sample consists of 1249
      healthy individuals (mean age = 47.7, SD = 16.8) from 404 nuclear families.
      Fifteen interrelated anthropometric measurements were transformed into two
      principal components, reflecting body size and mass. Those, plus circulating
      levels of PTH and OPG, were subjected to association analysis, using transmission
      disequilibrium tests (TDTs) with ANKH gene. From 805 to 1150 individuals per SNP
      were genotyped. RESULTS: In the proximal region (rs3006069-rs835154-rs835141),
      associations were found between the A-A-C haplotype and the first principal
      component reflecting body size (p < or = 0.048), whereas another haplotype, G-G
      C, was associated with the first principal component, reflecting the body mass (p
      < or = 0.008). In the distal region of ANKH (rs39968-rs696294-rs875525), the A-A
      C haplotype was found to be associated with OPG plasma levels (p < or = 0.001),
      whereas the G-A-C haplotype was associated with PTH circulating concentrations (p
      < or = 0.025). CONCLUSION: Taken together, the results show discrimination
      between the corresponding regions and haplotypes, suggesting trait-specific gene
      variants that influenced bone-related phenotypic variation in the studied
      population.

PMID- 18821331
TI  - Distribution of body mass index and the prevalence changes of overweight and
      obesity among adolescents in Shandong, China from 1985 to 2005.
AB  - BACKGROUND: There is strong evidence of a positive secular trend in physical
      growth and body mass index (BMI) in most of the world over the last 20 years.
      However, no studies on this trend have been reported in Shandong Province, China.
      AIM: The present study assessed the secular trend in BMI in Shandong Province
      during the past 20 years and the prevalence of overweight and obesity among
      adolescents. SUBJECTS AND METHODS: The BMI of adolescents aged 7-18 was
      calculated using data from three national surveys on students' constitution and
      health carried out by the government in 1985, 1995 and 2005 in Shandong Province,
      China. The distribution of BMI was reported, and the prevalence of overweight and
      obesity were obtained according to the screening criteria of overweight and
      obesity for Chinese students using BMI. RESULTS: In the past 20 years, the P(50)
      (percentile 50) of BMI increased rapidly. The average increments of BMI were 2.05
      kg m(-2) (Urban male), 1.08 kg m(-2) (Urban female), 1.11 kg m(-2) (Rural male)
      and 0.57 kg m(-2) (Rural female). The prevalence of overweight and obesity
      increased rapidly: for overweight from 3.08% (Urban male), 2.67% (Urban female),
      0.74% (Rural male) and 1.50% (Rural female) in 1985 to 17.52% (Urban male),
      10.56% (Urban female), 11.06% (Rural male) and 7.01% (Rural female) in 2005; and
      for obesity from 0.52% (Urban male), 0.36% (Urban female), 0.03% (Rural male) and
      0.11% (Rural female) in 1985 to 14.50% (Urban male), 6.79% (Urban female), 7.11%
      (Rural male) and 4.71% (Rural female) in 2005. CONCLUSION: The average value of
      BMI has increased over time; overweight and obesity among adolescents has become
      a serious public health problem. Comprehensive evidence-based strategies of
      intervention should be introduced, including periodic monitoring.

PMID- 18821332
TI  - HUMTH01, HUMVWA31A, HUMCSF1PO and HUMTPOX polymorphisms in Amerindian populations
      living in the Beni department of Bolivia.
AB  - This report presents allele frequency and absolute genotype data of the short
      tandem repeat (STR) loci HUMTH01, HUMVWA31A, HUMCSF1PO and HUMTPOX for three
      autochthonous Amerindian populations living in the Beni Department of Bolivia.
      These related groups are the Quechua, Aymara and Beni populations all living in
      specific although sometimes overlapping areas that extend from the Andean habitat
      to the lowland Llanos de Moxos savannah passing through the Piedmont hills. The
      usefulness of these loci for paternity and identification testing was also
      examined. The present work completes previous genetic studies performed by the
      authors in these populations including mtDNA haplogroups (Bert et al., Hum Biol,
      73:1-16, 2001) and HVRI data (Bert et al., Ann Hum Biol 31:9-28, 2004; Corella et
      al., Ann Hum Biol 34:34-35, 2007).

PMID- 18821333
TI  - Predictors of rate of weight gain in malnourished children within a
      realimentation programme.
AB  - The rate of weight gain of malnourished children in realimentation programmes
      varies substantially; however, predictors of variation are infrequently reported.
      The aim of this study was to assess a set of hypothesized predictors to the rate
      of weight gain of a sample of children attending a partial day treatment
      programme in the Dominican Republic. Data were available for 105 consecutive
      admissions (82% of total) to the programme between July 2004 and June 2006. Mean
      rate of weight gain, adjusted for initial weight, was 3.8 (SD 4.2) g kg(-1) day(
      1) during the first 28 days of treatment. Rate of weight gain was associated with
      the amount of calories consumed by the child from the enriched milk-based formula
      consumed within the clinic. This relationship depended upon the initial degree of
      wasting and the amount of diarrhoea, such that caloric intake had a greater
      impact on those with the most wasting and greater amounts of diarrhoea. Other
      hypothesized variables were not related to rate of weight gain. Further
      investigation is required to identify other predictors of the variability in
      weight gain within nutrition treatment programmes with tighter control of
      possible sources of measurement error.

PMID- 18821334
TI  - Noninvasive cardiac imaging: implications for risk assessment in adolescents and
      young adults.
AB  - Noninvasive imaging of cardiovascular end organ injury has now been applied to
      adolescents and young adults to better understand the early natural history of
      chronic heart disease. Echocardiography, assessment of endothelial function, and
      subclinical atherosclerosis imaging using carotid intima-media thickness measures
      and coronary calcium identified on computed tomography scanning have all been
      applied at young ages to demonstrate adverse effects of cardiovascular risk
      factors. Intervention trials using these techniques as end points may improve
      understanding of the natural history of acquired cardiovascular disease.

PMID- 18821335
TI  - Day care and attachment re-visited. Editorial.

PMID- 18821336
TI  - Attachment in US children experiencing nonmaternal care in the early 1990s.
AB  - This review paper presents and places in context findings from 23 manuscripts
      based on the data sets of the National Institute of Child Health and Human
      Development (NICHD) Study of Early Child Care and Youth Development (SECCYD). The
      NICHD study tracked the development of more than 1000 children from birth through
      age 15. The children were born across the USA to families that were diverse in
      terms of their economic, educational, and ethnic background. The children also
      varied in terms of the timing, extent, quality, and type of their child care
      experiences. The findings reported in this review paper pertain to (1) predictors
      of child-mother attachment; (2) links between child-mother attachment and
      children's developmental outcomes; and (3) methods for assessing attachment. The
      review paper also includes suggestions for future attachment research afforded by
      the data sets of the NICHD SECCYD. Not all the hypotheses tested in the reviewed
      papers were confirmed, and those that were confirmed were associated with modest
      effect sizes. Some findings emerged under specific conditions, even though they
      were expected to be more universal. These findings need to be discussed and
      aligned with theory. Also, the extent to which the findings generalize beyond the
      historical period and the country in which the data were collected merits
      discussion and exploration.

PMID- 18821337
TI  - Attachment to mother and nonmaternal care: bridging the gap.
AB  - In this commentary to the child-mother attachment findings of the NICHD Study of
      Early Child Care and Youth Development (SECCYD) we focus on the contextual
      conditions under which child care and the child's attachment relationship(s) may
      function as a risk or protective factor for child development. First, the
      authors' conclusion concerning child care as a risk factor for attachment
      security is refined. Second, suggestions are provided for incorporating possible
      moderators and mediators of the relations between child care, child-mother
      attachment, and developmental outcomes. Children's attachment relationship to
      nonmaternal caregivers, their temperament, and their genetic make-up may be
      relevant factors; and we discuss them in the context of children's differential
      susceptibility to influences from the caregiving environment. Third, and
      following from the above, we argue for specificity in predicting developmental
      outcomes from attachment security and nonmaternal care.

PMID- 18821338
TI  - Attachment and non-maternal care: towards contextualizing the quantity versus
      quality debate.
AB  - In this commentary to Friedman's and Boyle's review we focus on the context of
      early child care as it is reflected in the debate on the effects of quality of
      care versus amount of care and attachment relations. It is argued that cross
      national research should be considered along with the NICHD Study of Early Child
      Care and Youth Development (SECCYD) in order to promote better understanding of
      the interface of attachment, child care, and context. In addition, some
      methodological issues are discussed including the status of the Strange Situation
      assessment, definition of non-maternal care, and longitudinal correlates of
      attachment.

PMID- 18821339
TI  - Measure twice, cut once: attachment theory and the NICHD Study of Early Child
      Care and Youth Development.
AB  - The NICHD Early Child Care Research Network has produced research findings that
      provide reassuring confirmation of some central tenets of attachment theory,
      challenges to other aspects of the theory, and above all highlight the need for
      attachment researchers to clarify the claims for which the theory can be held
      accountable. This commentary on Friedman and Boyle's excellent review evaluates
      the strengths and weaknesses of the NICHD Study of Early Child Care and Youth
      Development as a study of attachment, and highlights the relevance of these
      findings for understanding the origins and consequences of attachment security,
      the problem of heterotypic continuity of the attachment construct, the importance
      of examining mediators and moderators of the developmental influence of security,
      and the interpretation of modest effect sizes from the study.

PMID- 18821340
TI  - Changes in maternal sensitivity across the first three years: are mothers from
      different attachment dyads differentially influenced by depressive
      symptomatology?
AB  - Hierarchical linear modeling was used to describe longitudinal relations between
      maternal sensitivity and depressive symptomatology for mothers of children with
      differing attachment classifications at 36 months of child age using data from
      the NICHD Study of Early Child Care. Attachment during toddlerhood was assessed
      using a modified Strange Situation Paradigm developed by the MacArthur Working
      Group on Attachment. On average, maternal sensitivity increased longitudinally
      from 6 to 36 months for groups with children classified as secure or resistant,
      but not for groups classified as avoidant or disorganized. Higher maternal
      depressive symptoms were associated with lower levels of sensitivity for all
      mothers, although this effect was significantly less severe for mothers of
      securely attached children. In addition, higher maternal depressive symptoms were
      associated with decreases in sensitivity from 6 to 36 months for mothers of
      children who at 36 months showed disorganized attachments combined with
      underlying patterns of avoidant or resistant behavior.

PMID- 18821341
TI  - Attachment security and parenting quality predict children's problem-solving,
      attributions, and loneliness with peers.
AB  - The influence of early relational experience on later social understanding has
      evoked rich theoretical discussion but relatively little empirical inquiry.
      Enlisting data from the NICHD Study of Early Child Care and Youth Development,
      measures of the security of attachment in infancy, toddlerhood, and early
      childhood, together with measures of parenting quality (maternal sensitivity and
      depressive symptoms) gathered longitudinally throughout infancy and early
      childhood, were used to predict differences in children's thoughts and feelings
      about peers (i.e., social problem solving, negative attributional biases,
      aggressive solutions to ambiguous social situations, and self-reported
      loneliness) when children were 54 months and in first grade. Relational
      experiences, especially before 36 months, were significantly predictive of later
      peer-related representations. Attachment security at 24 and 36 months was
      associated with enhanced social problem-solving skills and less loneliness, but
      security of attachment at 15 months was nonpredictive. Early maternal sensitivity
      was positively associated with later social problem-solving and negatively with
      aggressive responses, and early maternal depressive symptoms were positively
      associated with children's negative attributions. Concurrent parenting quality
      was also associated with children's thoughts and feelings about peers, but less
      consistently. These findings shed new light on how early relational experiences
      may contribute to social information processing with peers at the end of the
      preschool years, and that the timing of relational influences may be crucial.

PMID- 18821342
TI  - The eight articles finally selected reflect the range of high-quality research
      presented at MICCAI 2007.

PMID- 18821343
TI  - Cardiolock: an active cardiac stabilizer. First in vivo experiments using a new
      robotized device.
AB  - Off-pump Coronary Artery Bypass Grafting (CABG) is still a technically difficult
      procedure. The mechanical stabilizers used for local suppression of the heart
      excursion have been demonstrated to exhibit significant residual motion, which
      could lead to a lack of accuracy in performing the surgical task, particularly
      when using a minimally invasive surgery (MIS) approach. We therefore propose a
      novel active stabilizer to compensate for the residual motion whose architecture
      is compatible with MIS. An experimental evaluation of a commercially available
      totally endoscopic stabilizer is first presented to demonstrate the
      unsatisfactory behavior of this device. Then, the interaction between the heart
      and a mechanical stabilizer is assessed in vivo using an animal model. Finally,
      the principle of active stabilization, based on the high-speed vision-based
      control of a piezo-actuated compliant mechanism, is presented, along with in vivo
      experimental results obtained using a prototype to demonstrate its efficiency.

PMID- 18821344
TI  - Real-time MRI-TRUS fusion for guidance of targeted prostate biopsies.
AB  - Targeted prostate biopsy is challenging because no currently established imaging
      modality is both accurate for prostate cancer diagnosis and cost-effective for
      real-time procedure guidance. A system that fuses real-time transrectal
      ultrasound images with previously acquired endorectal coil MRI images for
      prostate biopsy guidance is presented here. The system uses electromagnetic
      tracking and intraoperative image registration to superimpose the MRI data on the
      ultrasound image. Prostate motion is tracked and compensated for without the need
      for fiducial markers. The accuracy of the system in phantom studies was shown to
      be 2.4 +/- 1.2 mm. The fusion system has been used in more than 20 patients to
      guide biopsies with almost no modification of the conventional protocol.
      Retrospective clinical evaluation suggests that clinically acceptable spatial
      accuracy can be achieved.

PMID- 18821345
TI  - Needle-tissue interaction modeling using ultrasound-based motion estimation:
      phantom study.
AB  - Needle insertion simulators find use in a number of medical interventions, such
      as prostate brachytherapy. A needle insertion simulator has three main
      components: the needle model, the tissue model, and the model of interaction
      between the needle and the tissue. In this paper, a new methodology is introduced
      for the joint modeling of tissue and needle-tissue interactions. The approach
      consists of the measurement of tissue motion using ultrasound, and of the needle
      position and base force. Tissue motion is determined using a correlation-based
      algorithm that processes the ultrasound radiofrequency data. The tissue elastic
      parameters and the parameters of the tissue-needle interaction model are
      determined by using numerical optimization to match the response of the needle
      insertion model to the measured data. Phantom experiments were carried out in
      which a brachytherapy needle was inserted into a two-layer non-homogeneous
      phantom mimicking a prostate and its surrounding tissue. Experimental results
      show good agreement with the model obtained. In particular, the parameters of a
      three-parameter force model were identified for each layer of the phantom to fit
      the measured force to the simulated one. Also, the Young's modulus of each layer
      was identified to match the measured and simulated nodal axial displacements.
      This is the first report of the use of ultrasound radiofrequency data to
      characterize tissue motion during needle insertion. As the method is non-invasive
      and does not involve ionizing radiation, its application in patient studies is
      feasible.

PMID- 18821346
TI  - Combining a breathing model and tumor-specific rigidity constraints for
      registration of CT-PET thoracic data.
AB  - Diagnosis and therapy planning in oncology applications often rely on the joint
      exploitation of two complementary imaging modalities, namely Computerized
      Tomography (CT) and Positron Emission Tomography (PET). While recent technical
      advances in combined CT/PET scanners enable 3D CT and PET data of the thoracic
      region to be obtained with the patient in the same global position, current image
      data registration methods do not account for breathing-induced anatomical changes
      in the thoracic region, and this remains an important limitation. This paper
      deals with the 3D registration of CT thoracic image volumes acquired at two
      different instances in the breathing cycle and PET volumes of thoracic regions.
      To guarantee physiologically plausible deformations, we present a novel method
      for incorporating a breathing model in a non-linear registration procedure. The
      approach is based on simulating intermediate lung shapes between the two 3D lung
      surfaces segmented on the CT volumes and finding the one most resembling the lung
      surface segmented on the PET data. To compare lung surfaces, a shape registration
      method is used, aligning anatomical landmark points that are automatically
      selected on the basis of local surface curvature. PET image data are then
      deformed to match one of the CT data sets based on the deformation field provided
      by surface matching and surface deformation across the breathing cycle. For
      pathological cases with lung tumors, specific rigidity constraints in the
      deformation process are included to preserve the shape of the tumor while
      guaranteeing a continuous deformation.

PMID- 18821347
TI  - Endoscopic navigation for minimally invasive suturing.
AB  - Manipulating small objects such as needles, screws or plates inside the human
      body during minimally invasive surgery can be very difficult for less experienced
      surgeons due to the loss of 3D depth perception. Classical navigation techniques
      are often incapable of providing support in such situations, as the augmentation
      of the scene with the necessary artificial markers--if possible at all--is
      usually cumbersome and leads to increased invasiveness. We present an approach
      relying solely on a standard endoscope as a tracking device for determining the
      pose of such objects, using the example of a suturing needle. The resulting pose
      information is then used to generate artificial 3D cues on the 2D screen to
      provide optimal support for surgeons during tissue suturing. In addition, if an
      external tracking device is provided to report the endoscope's position, the
      suturing needle can be directly tracked in the world coordinate system.
      Furthermore, a visual navigation aid can be incorporated if a 3D surface is
      intraoperatively reconstructed from the endoscopic video stream or registered
      from preoperative imaging.

PMID- 18821348
TI  - New approaches to online estimation of electromagnetic tracking errors for
      laparoscopic ultrasonography.
AB  - In abdominal surgery, a laparoscopic ultrasound transducer is commonly used to
      detect lesions such as metastases. The determination and visualization of the
      position and orientation of its flexible tip in relation to the patient or other
      surgical instruments can be a great support for surgeons using the transducer
      intraoperatively. This difficult subject has recently received attention from the
      scientific community. Electromagnetic tracking systems can be applied to track
      the flexible tip; however, current limitations of electromagnetic tracking
      include its accuracy and sensibility, i.e., the magnetic field can be distorted
      by ferromagnetic material. This paper presents two novel methods for estimation
      of electromagnetic tracking error. Based on optical tracking of the laparoscope,
      as well as on magneto-optic and visual tracking of the transducer, these methods
      automatically detect in 85% of all cases whether tracking is erroneous or not,
      and reduce tracking errors by up to 2.5 mm.

PMID- 18821349
TI  - Imagination and integrity: decision-making among lesbian couples to use medically
      provided donor insemination.
AB  - This paper reports findings from a pilot study of lesbian parents in the UK who
      used medicalised donor insemination (DI) with unknown donors. It focuses on
      decision-making processes in family construction: this includes lesbian parents'
      experiences with clinicians and their family stories as told to clinicians and to
      their young children. Findings reveal that parents' understanding of family,
      particularly the centrality of the lesbian couple as the key parenting
      relationship, is crucial. We suggest that this group of parents make considered
      decisions about how their family might be created. It is their perception of what
      family means and their desire to protect the integrity of their family that leads
      them to negotiate social questions, particularly in relation to the presence of a
      'father' and the familial role/relationship of the non-biological parent. The
      study calls attention to the process of respondents' reflexivity about family and
      their 'doing' of family and highlights the integrity and imagination central to
      becoming lesbian parents.

PMID- 18821350
TI  - 'It's like the treasure': beliefs associated with semen among young HIV-positive
      and HIV-negative gay men.
AB  - This paper examines cultural and social meanings associated with semen, along
      with related issues of unprotected receptive anal intercourse, HIV
      seroconversion, treatment optimism and viraemia. The findings are derived from
      qualitative interviews conducted with 12 HIV-positive young gay men and 12 HIV
      negative counterparts who participated in a prospective cohort study in
      Vancouver, Canada. Focussing on the narratives of young gay men, the analysis
      reveals a diverse range of knowledge, values and functions of semen, especially
      in relation to its exchange. Beliefs about semen appeared to differ by HIV
      serostatus and were linked with intimacy, identity and pleasure, particularly
      among the HIV-positive men. Against dominant representations of semen in relation
      to issues of loss, anxiety and infertility, this unique study sheds much needed
      light on its role within the cultural construction of sexuality among gay men. As
      such, these narratives are of direct importance to primary and secondary HIV
      prevention, including condom promotion and the development of rectal
      microbicides.

PMID- 18821351
TI  - Gender, culture and harm: an exploratory study of female heroin users of
      Vietnamese ethnicity.
AB  - Previous quantitative cross sectional studies of ethnic Vietnamese drug users in
      Melbourne have been overwhelmingly drawn from samples of men. In this qualitative
      investigation, 24 women aged between 18 and 33 years were interviewed. This
      exploratory study sought: to identify issues surrounding heroin initiation and
      drug use career; to examine relationships with family and primary sex partners;
      and to reveal participants' attitudes to drug treatment. Data reveal that for the
      women in this study the initiation and continued use of heroin was heavily
      influenced by men, especially their primary sex partners. The women interviewed
      reported strategies to minimise their risk taking including enrolling in
      pharmacotherapy treatment programmes, but they remained particularly vulnerable -
      especially to blood borne viruses - through both injecting and sexual risk
      behaviour. The data suggest that interventions which focus on the gendered nature
      of injecting practices within personal relationships may go some way to both
      reducing harm and increasing control for the women involved.

PMID- 18821352
TI  - 'Too many girls, too much dowry': son preference and daughter aversion in rural
      Tamil Nadu, India.
AB  - The southern Indian state of Tamil Nadu has experienced a dramatic decline in
      fertility, accompanied by a trend of increased son preference. This paper reports
      on findings from qualitative interviews with women in rural villages about their
      fertility decision-making. Specifically addressed are the reasons behind
      increasing son preference and the consequences of this change. Findings suggest
      that daughter aversion, fuelled primarily by the perceived economic burden of
      daughters due to the proliferation of dowry, is playing a larger role in
      fertility decision-making than son preference. The desire for a son is often
      trumped by the worry over having many daughters. Women use various means of
      controlling the sex of their children, which in this study appear to be primarily
      female infanticide. It is important to distinguish between son preference and
      daughter aversion and to examine repercussions of low fertility within this
      setting.

PMID- 18821353
TI  - 'Always between two cultures': young British Bangladeshis and their mothers'
      views on sex and relationships.
AB  - This paper presents data on the sexual health perspectives of young British
      Bangladeshis and their mothers. It discusses the implications of these data for
      the development of appropriate sexual health education. Between April and
      September 2006, 36 young people and 25 mothers of Bangladeshi young people were
      interviewed through seven focus group discussions. Groups were gender and age
      specific (16-18 years, 19-20 years and mothers). Recruitment took place in
      community-based organisations in an inner city London borough. Mothers expressed
      concern about pre-marital sex but felt unable to control out-of-home activity.
      Feelings of isolation, lack of control and communication difficulties were key
      issues for them. Young people had varied perspectives on pre-marital sex. Some
      experienced emotional conflict between what was expected of them in terms of
      their faith and their engagement in intimate relationships. Both the young people
      and mothers highlighted the need for sex and relationship education to take
      account of cultural perspectives and the involvement of parents and the wider
      community. However, parents and community representatives require information and
      communication support to enable this involvement. Sex and relationships education
      content needs to be inclusive, have both secular and faith perspectives and
      engage where relevant with local communities.

PMID- 18821354
TI  - Beyond stigma? Young children's responses to HIV and AIDS.
AB  - This paper explores the manifestation of HIV-related stigma in seven- and eight
      year-old white South African children's responses to HIV and AIDS. Drawing from
      elements of ethnographic and interview data, it shows how young children's
      responses to HIV and AIDS are inscribed within popular accounts of contagion and
      articulate gendered, sexual, raced and classed discourses in South Africa.
      Rejecting static accounts of stigma, the paper shows how children resist and
      confirm power inequalities involving intense self-regulation as well as
      inscribing within discourses of care and concern for others infected with HIV and
      AIDS. The findings have implications for scaling up educational efforts to
      address awareness of HIV and AIDS and stigma, but also to build on positive
      insights that young children demonstrate with regard to the disease.

PMID- 18821355
TI  - After the fall from grace: negotiation of new identities among HIV-positive women
      in Peru.
AB  - Despite increasing rates of HIV infection among heterosexual women in Peru,
      married women remain virtually invisible as a group at risk of HIV or requiring
      treatment. This study analyzed the intersections of HIV with machismo and
      marianismo, the dominant discourses in Latin America that prescribe gender roles
      for men and women. Data sources include recent literature on machismo and
      marianismo and interviews conducted with 14 HIV-positive women in Lima, Peru.
      Findings indicate how the stigma associated with HIV constructs a discourse that
      restricts the identities of HIV-positive women to those of 'fallen women' whether
      or not they adhere to social codes that shape and inform their identities as
      faithful wives and devoted mothers. Lack of public discourse concerning HIV
      positive marianas silences women as wives and disenfranchises them as mothers,
      leaving them little room to negotiate identities that allow them to maintain
      their respected social positions. Efforts must be aimed at expanding the
      discourse of acceptable gender roles and behaviour for both men and women within
      the context of machismo and marianismo so that there can be better recognition of
      all persons at risk of, and living with, HIV infection.

PMID- 18821358
TI  - Could cord blood be a source of mesenchymal stromal cells for clinical use?
AB  - BACKGROUND: Cord blood (CB) has long been regarded as an easily accessible source
      of hematopoietic progenitors suitable for transplantation, but its efficiency as
      a source of mesenchymal stromal cells (MSC) remains controversial. The aim of
      this study was to assess CB as a potential source of MSC, to determine the
      optimal culture requirements for CB MSC expansion and to compare their functional
      and immunophenotypic characteristics with bone marrow (BM) MSC from children.
      METHODS: Mononuclear cells from 18 full-term CB samples and 23 BM samples from
      children were set in culture under MSC-inducing conditions. Their
      immunophenotypic characteristics were assessed by flow cytometry and their
      differentiation potential was evaluated. RESULTS: Isolation of CB MSC was
      achieved in 25% of the samples cultured under optimal conditions: high initial
      cell concentration, fetal calf serum (FCS) enrichment of the culture medium, high
      FGF-2 concentration and high sample volume. Isolated CB MSC were morphologically
      similar to the ones derived from BM, but appeared late in culture. An adherent
      cell layer was formed and reached confluency in 34 days (passage 1; P1) and
      needed 55 days subsequently (from P1 to P2). CB MSC retained their
      characteristics for two successive passages. Immunophenotypic analysis showed no
      expression of CD34 and varying expression of CD45, ranging from 0% to 17.83%, and
      CD105, from 49% to 83%. CFU-F colonies developed in one case. DISCUSSION: These
      findings suggest that CB cannot be considered a sufficient source of MSC for
      clinical use, although easily accessible. Further research should aim for
      alternative sources.

PMID- 18821359
TI  - IMMUNEPOTENT CRP (bovine dialyzable leukocyte extract) adjuvant immunotherapy: a
      phase I study in non-small cell lung cancer patients.
AB  - BACKGROUND: IMMUNEPOTENT CRP is a mixture of low molecular weight substances,
      some of which have been shown to be capable of modifying the immune response. We
      evaluated the response and adjuvant effect of IMMUNEPOTENT CRP on non-small cell
      lung cancer (NSCLC) patients in a phase I clinical trial. METHODS: Twenty-four
      NSCLC patients were included in the study and divided into two groups. Group 1
      received a conventional treatment of 5400 cGy external radiotherapy in 28
      fractions and chemotherapy consisting of intravenous cisplatin (40 mg/m(2))
      delivered weekly for 6 weeks. Group 2 received the conventional treatment plus
      IMMUNEPOTENT CRP (5 U) administered daily. We performed clinical evaluation by CT
      scan and radiography analysis, and determined the quality of life of the patients
      with the Karnofsky performance scale. A complete blood count (red and white blood
      cell tests), including flow cytometry analysis, blood work (alkaline phosphatase
      test) and a delayed-type hypersensitivity (DTH) skin test for PPD, Varidase and
      Candida were performed. RESULTS: The administration of IMMUNEPOTENT CRP induced
      immunomodulatory activity (increasing the total leukocytes and T-lymphocyte
      subpopulations CD4(+), CD8(+), CD16(+) and CD56(+), and maintaining DHT) and
      increased the quality of the patients' lives, suggesting immunologic protection
      against chemotherapeutic side-effects in NSCLC patients. DISCUSSION: Our results
      suggest the possibility of using IMMUNEPOTENT CRP alongside radiation and
      chemotherapy for maintaining the immune system and increasing the quality of life
      of the patients.

PMID- 18821360
TI  - Flanking-sequence exponential anchored-polymerase chain reaction amplification: a
      sensitive and highly specific method for detecting retroviral integrant-host
      junction sequences.
AB  - BACKGROUND: Retroviral vectors are regularly used to transduce stem cells and
      their derivatives for experimental and therapeutic purposes. Because these
      vectors integrate semi-randomly into the cellular genome, analysis of
      integranated retroviral DNA/host cell DNA junctions (IHJ) facilitates clonality
      studies of engrafted cells, allowing their differentiation, survival and fate to
      be tracked. In the case of any adverse events, IHJ analysis can allow the
      identification of potentially oncogenic integration sites. At present, most
      measures to assess IHJ are complex, insensitive and may be subject to IHJ
      selection bias inherent to the technology used. METHODS: We have developed and
      validated a simple but effective technique for generating libraries of IHJ, which
      we term flanking-sequence exponential anchored-polymerase chain reaction (FLEA
      PCR). Flanking-sequence random anchoring is used as an alternative to restriction
      enzyme digestion and cassette ligation to allow consistent detection of IHJ and
      decrease bias. RESULTS: Individual clones from plasmid libraries can be sequenced
      and assembled using custom-written software, and FLEA-PCR smears can be analyzed
      by capillary electrophoresis after digestion with restriction enzymes.
      DISCUSSION: This approach can readily analyze complex mixtures of IHJ, allowing
      localization of these sequences to their genomic sites. This approach should
      simplify analysis of retroviral integration.

PMID- 18821361
TI  - Diagnosed eating disorders in the U.S. Military: a nine year review.
AB  - The objective of this study was to determine the incidence of three types of
      eating disorders (ED); anorexia nervosa (AN), bulimia nervosa (BN) and eating
      disorder not otherwise specified (EDNOS), diagnosed in the U.S. Military.
      Diagnosed cases of ED were obtained from the Defense Medical Epidemiology
      Database for all Service Members (SM) from 1998-2006. The percentage per year of
      SM with an ED diagnosis was .30%. Eating disorders were diagnosed significantly
      more in 2006 (.41%) compared to 1998 (.23%) (p < .001). Females were diagnosed
      significantly more than males (p < .001). The majority of AN cases (66%) were in
      the Marines. This is the first known study to investigate the incidence of ED in
      SM using medical record data. Service Members diagnosed with ED have increased.
      Females, specifically White females, have higher incidence of ED. The reported
      incidence of diagnosed ED in SM was lower compared to previous research.

PMID- 18821362
TI  - Integrating evidence-based treatments with individual needs in an outpatient
      facility for eating disorders.
AB  - The purpose of this study was to evaluate the effectiveness of a day treatment
      program for 77 women diagnosed with eating disorders. The program utilizes an
      integrative approach, combining evidence-based treatments such as cognitive
      behavioral therapy with clinical experience and additional multimodal
      interventions based on individual needs. Three modes of treatment used in the
      program (group therapy, family therapy, and individual therapy) and two levels of
      treatment (partial hospitalization and intensive outpatient) are described in
      detail. The effectiveness of the treatment program was evaluated by comparing pre
      treatment and post-treatment data on outcome measures for eating disorder
      attitudes, personality characteristics, and symptoms, as well as depressive
      symptoms and anxiety symptoms. Results indicated that after an average of 12.8
      weeks of treatment, patients reported a significant reduction in eating disorder
      symptoms, depressive symptoms, and anxiety symptoms, and a significant increase
      in weight at post-treatment. Implications of these findings and directions for
      future research are discussed.

PMID- 18821363
TI  - Participation in athletic activities and eating disordered behavior.
AB  - The purpose of the following study was to examine the relationship between
      participation in athletic and exercise activities and eating disordered behavior
      among a college student population. A sample of 853 undergraduate students
      completed the EAT-26 and indicated participation in athletic activities to
      determine eating disorder-related dieting and exercise attitudes and behaviors.
      Results demonstrate that participation in recreational activities correlates with
      more deleterious attitudes than involvement in organized sports. Implications for
      counseling and prevention are discussed.

PMID- 18821364
TI  - Emotion regulation skills mediate the effects of shame on eating disorder
      symptoms in women.
AB  - We examined the impact of negative affectivity, chronic shame, and emotion
      regulation skills on eating disorder symptoms in undergraduate women (N = 154).
      We hypothesized that self-reported emotion regulation skills would mediate the
      well-documented relationship between chronic shame and eating disorder symptoms.
      Results revealed that chronic shame predicted eating disorder symptoms over and
      above general negative affectivity. Further, difficulties with emotion regulation
      mediated the relationship between chronic shame and ED symptoms. These findings
      suggest that chronic shame's role in eating disorder symptoms can be ameliorated
      by skillful emotion regulation.

PMID- 18821365
TI  - A randomized experimental test of the efficacy of EMDR treatment on negative body
      image in eating disorder inpatients.
AB  - Eye Movement Desensitization and Reprocessing (EMDR) therapy is being used by
      some clinicians to treat eating disorders. Although there is anecdotal and case
      study data supporting its use, there are no controlled studies examining its
      effectiveness with this population. This study examined the short and long-term
      effects of EMDR in a residential eating disorders population. A randomized,
      experimental design compared 43 women receiving standard residential eating
      disorders treatment (SRT) to 43 women receiving SRT and EMDR therapy (SRT+EMDR)
      on measures of negative body image and other clinical outcomes. SRT+EMDR reported
      less distress about negative body image memories and lower body dissatisfaction
      at posttreatment, 3-month, and 12-month follow-up, compared to SRT. Additional
      comparisons revealed no differences between the conditions pre to posttreatment
      on other measures of body image and clinical outcomes. The empirical evidence
      reported here suggests that EMDR may be used to treat specific aspects of
      negative body image in conjunction with SRT, but further research is necessary to
      determine whether or not EMDR is effective for treating the variety of eating
      pathology presented by eating disorder inpatients.

PMID- 18821366
TI  - Eating disorders awareness week: the effectiveness of a one-time body image
      dissatisfaction prevention session.
AB  - The purpose of this study was to assess the effectiveness of a body image
      dissatisfaction prevention session that provided information on body image and
      media literacy to college women. Participants were 81 undergraduates who were
      randomly assigned to attend either a body image intervention or a control
      intervention. Participants completed measures at pre- and post-intervention and
      at 4-week follow-up. The body image group improved significantly more than the
      control group on body shape concerns, but not on the other outcome variables.
      Efficacious interventions capable of reaching large numbers of women are
      necessary to help dispel the "normative discontent" prevalent today.

PMID- 18821367
TI  - Effects of being a peer-leader in an eating disorder prevention program: can we
      further reduce eating disorder risk factors?
AB  - Studies regarding the effect of peer-leadership on peer-leaders in prevention
      programs remain extremely limited. In this study, 83 undergraduate sorority
      members, who previously participated in the program, served as peer-leaders for
      an eating disorder prevention program. Peer-leaders attended 9 hours of training
      and then led two 2-hour sessions. Leaders showed decreases (beyond participation
      in earlier studies) in dietary restraint, bulimic pathology, body
      dissatisfaction, and thin-ideal internalization from pre-training through 7-week
      follow up. Results from this exploratory study suggest that peer-leaders who
      participate in a program and subsequently lead it may experience additional
      benefits compared to participation in the program alone.

PMID- 18821371
TI  - Risk factor analysis of diarrhoeal diseases in the Aral Sea area (Khorezm,
      Uzbekistan).
AB  - In the Aral Sea basin, human activities have resulted in the severe degradation
      of water and soil, which is considered to cause serious human health problems.
      This study investigated the risk factors: water, sanitation and related hygiene
      issues for diarrhoeal disease in Khorezm province, Uzbekistan. The risk factors
      were studied using a combination of quantitative and qualitative methods
      including water quality monitoring, standardised questionnaires and spot checks.
      Multiple linear regression analysis revealed that visible contamination of
      drinking water during storage and the absence of anal cleansing materials were
      significantly associated with the number of diarrhoeal episodes per household.
      Overall, the findings of the study show that the domestic domain plays a major
      role with regard to faecal-oral disease transmission in Khorezm, Uzbekistan.
      Unhealthy excreta disposal habits and unsafe drinking water storage practices
      have to be urgently tackled in order to break the faecal-oral transmission route.

PMID- 18821372
TI  - Climate influence on dengue epidemics in Puerto Rico.
AB  - The variability of the insect-borne disease dengue in Puerto Rico was studied in
      relation to climatic variables in the period 1979-2005. Annual and monthly
      reported dengue cases were compared with precipitation and temperature data.
      Results show that the incidence of dengue in Puerto Rico was relatively constant
      over time despite global warming, possibly due to the offsetting effects of
      declining rainfall, improving health care and little change in population.
      Seasonal fluctuations of dengue were driven by rainfall increases from May to
      November. Year-to-year variability in dengue cases was positively related to
      temperature, but only weakly associated with local rainfall and an index of El
      Nino Southern Oscillation (ENSO). Climatic conditions were mapped with respect to
      dengue cases and patterns in high and low years were compared. During epidemics,
      a low pressure system east of Florida draws warm humid air over the northwestern
      Caribbean. Long-term trends in past observed and future projected rainfall and
      temperatures were studied. Rainfall has declined slowly, but temperatures in the
      Caribbean are rising with the influence of global warming. Thus, dengue may
      increase in the future, and it will be necessary to anticipate dengue epidemics
      using climate forecasts, to reduce adverse health impacts.

PMID- 18821373
TI  - Water disinfection and hygiene behaviour in an urban slum in Kenya: impact on
      childhood diarrhoea and influence of beliefs.
AB  - In this research project, we studied factors that presumably affect the incidence
      of diarrhoea among young children in urban slums in developing countries:
      consumption of safe drinks, hygiene behaviour, cleanliness of household
      surroundings and the quality of raw water. Beliefs concerning the causes of
      diarrhoea were also related to health-improving behaviour, namely the application
      of the water-treatment method SODIS (solar water disinfection) and hygiene
      behaviour. We conducted a survey in a shanty town in Nairobi, Kenya. Field
      workers interviewed 500 households. Analysis with regression models revealed that
      two out of the four postulated factors were significant: children have a lower
      risk of contracting diarrhoea when they consume high percentages of safe drinks
      and live in households with good hygiene. As regards beliefs, we found that
      biomedical knowledge of children's diarrhoea as well as the perceived social norm
      for treating water was associated with the use of SODIS and good hygiene.

PMID- 18821374
TI  - Monitoring environmental cleanliness on two surgical wards.
AB  - Ten hand-touch sites were screened weekly on two surgical wards over two
      consecutive six-month periods. The results were analysed using hygiene standards,
      which specify (i) an aerobic colony count (ACC) > 2.5 cfu/cm(2), and (ii)
      presence of coagulase-positive staphylococci, as hygiene failures. Sites most
      often failing the standards were beds and hoist (64%: 33 of 52 weeks), bedside
      lockers (62%: 32 of 52) and overbed tables (44%: 23 of 52). Methicillin
      susceptible/resistant Staphylococcus aureus (MSSA/MRSA) were more often recovered
      from lockers, overbed tables and beds. Recovery of MSSA/MRSA at any site was
      significantly associated with an ACC > 2.5 cfu/cm(2) from that site (p = 0.001;
      OR: 3.35 [95% CI 1.79, 6.28]). In addition, total ACC's > 2.5 cfu/cm(2) each week
      were significantly associated with weekly bed occupancies > 95% (p = 0.0004; OR:
      2.94 [95% CI 1.44, 6.02]). Higher microbial growth levels from hand-touch sites
      reflect weekly bed occupancies and indicate a risk for both resistant and
      susceptible S. aureus. These organisms are more likely to be recovered from near
      patient sites on the ward.

PMID- 18821375
TI  - Food hygiene training in small to medium-sized care settings.
AB  - Adoption of safe food handling practices is essential to effectively manage food
      safety. This study explores the impact of basic or foundation level food hygiene
      training on the attitudes and intentions of food handlers in care settings, using
      questionnaires based on the Theory of Planned Behaviour. Interviews were also
      conducted with food handlers and their managers to ascertain beliefs about the
      efficacy of, perceived barriers to, and relevance of food hygiene training. Most
      food handlers had undertaken formal food hygiene training; however, many who had
      not yet received training were preparing food, including high risk foods.
      Appropriate pre-training support and on-going supervision appeared to be lacking,
      thus limiting the effectiveness of training. Findings showed Subjective Norm to
      be the most significant influence on food handlers' intention to perform safe
      food handling practices, irrespective of training status, emphasising the role of
      important others in determining desirable behaviours.

PMID- 18821376
TI  - Water quality and improving hygienic practices of the rural community in the
      vicinity of Ramallah, West Bank, Palestine.
AB  - The study aims to increase community awareness at the household level about
      certain hygienic practices and water quality in order to develop an effective
      program that will target improving specific hygiene-related behavior. The study
      was carried out in two Palestinian villages and applies a quasi-experimental
      design where chemical and biological water quality analysis as well as
      residential behavioral aspects related to some hygiene practices were assessed
      before and after envisaged intervention applications. A questionnaire was used to
      evaluate the housewives' knowledge, and practices in regard to hygienic practices
      and water use, followed by face-to-face health education and awareness sessions
      to the selected housewives. After 3 months, another assessment was conducted
      using the same questionnaire to measure improvement in their knowledge and
      practices. On the first visit, in addition to collecting data related to the
      questionnaire, the water quality in the selected houses was tested to ensure the
      quality aspects of the hygiene practices. Based on these findings, the chosen
      methodology was able to promote a real change in improving the water quality on
      household taps and in improving hygienic practices and knowledge.

PMID- 18821377
TI  - Unintentional child home injury incidence and patterns in six countries in
      Europe.
AB  - This study investigates the incidence and patterns of child home injuries in six
      European Union countries. Emergency department and inpatient injury data on
      injuries to children aged 0-18 years in the home (n = 88,567) for the years 2003
      2004 were extracted from the European Injury Database in Austria, Denmark,
      France, Netherlands, Portugal and Sweden. The incidence of child home injuries
      was 44.9/1000 inhabitants Six age-dependent injury patterns were identified using
      cluster analysis: 1) open wound head injuries; 2) hospital admissions for
      bruises, contusions, abrasions; 3) falls on stairs indoors; 4) fractures and
      sprains of the upper extremities; 5) crush/cut/piercing of the fingers; 6)
      miscellaneous injuries. Child home injuries are a considerable public health
      problem, particularly in the ages 0 to 4 years. The findings are useful for
      injury surveillance at the European level yet do not allow for designing testable
      countermeasures for prevention within home safety initiatives.

PMID- 18821378
TI  - Latino families report lower child injury rates than white families.
AB  - Latino children have lower visit rates to emergency departments and primary care
      physicians than white children in the USA. Using a nationally representative
      household survey, this study asked whether parental report of injury was also
      lower for Latino children, after adjusting for demographic, socioeconomic, health
      status and health care access factors. Data were obtained on injuries for which
      medical advice or treatment was received from the National Health Interview
      Survey (NHIS) from 1997 to 2003. Using the multistage probability design of NHIS,
      annual rates and adjusted odds of childhood injury report by race and ethnicity
      were calculated. Respondents reported lower rates of injury for Latino children
      (6.0 (95% CI 5.3-6.8)/100 person-years) than white children (13.4 (12.7-14.2)/100
      person-years). Lower injury rates were mainly due to lower rates of sports
      injuries and accidental falls. Latino children had lower odds of reported injury
      than white children, even after adjusting for multiple factors (odds ratio 0.7;
      95% CI 0.6-0.8). Lower odds of injury report among Latino children are
      independent of direct measures of demographic, socioeconomic, health status and
      health care access factors and indirect measures of acculturation including
      respondent language and country of origin. Potential explanations include lower
      exposure to risk, greater child supervision, reporting bias, differences in
      cultural attitudes toward seeking of health care and reduced health care access
      that cannot be explored in NHIS due to the form of the current questions. Further
      research is needed to investigate cultural differences in risk exposure, child
      supervision and seeking of injury care.

PMID- 18821379
TI  - The appropriate and inappropriate use of child restraint seats in Manitoba.
AB  - The objective of this research was to describe the use and incorrect use of child
      restraint systems in Manitoba, Canada. In 2004, a team of inspectors made up of
      Royal Canadian Mounted Police officers and trained car seat technicians from the
      Manitoba child seat coalition conducted a descriptive survey of types and
      frequency of child restraint systems' incorrect use. The setting was 10 roadside
      inspection sites located around the city of Winnipeg, Manitoba. The subjects were
      parents and primary caregivers of children using child restraint systems. The
      main outcome measured was the reported appropriate use rate as determined by the
      compliance to safety standards for correct installation and use of child
      restraints. A total of 340 child restraint systems were assessed. The overall
      rate of incorrect use was 70%. The errors present in stage III systems (booster
      seats) are much lower than the errors present in stage I systems (rear-facing
      child safety seats) and stage II systems (forward-facing child safety seats). The
      data presented illustrate that incorrect use of child restraint systems in the
      province of Manitoba is a large problem and must be dealt with immediately in
      order to ensure child safety now and in the future. Community-wide information
      and enhanced enforcement campaigns, consisting of activities such as mass media,
      information and publicity, child restraint systems displays and special
      enforcement strategies (check points, dedicated law enforcement officials,
      alternative penalties) should be used to increase the correct use of child
      restraint systems. Failure to use child restraint systems properly can contribute
      to serious injury or death of a child.

PMID- 18821380
TI  - The association of psychological symptoms with unintentional injuries among
      retired employees of a university in China.
AB  - To investigate the association of psychological symptoms with injury risk,
      psychological symptoms were measured using symptom checklist-90 revised (SCL-90
      R) and the unintentional injury information was followed up for 1 year among
      retired employees at a university in China. The injury rate had a significant
      difference between groups of raw mean score > or =2.0 and <2.0 for SCL-90-R
      global factor and subscale factors of obsessive compulsiveness, interpersonal
      sensitivity, depression and anxiety. After accounting for the factors of daily
      housework, physical activities, living alone and demographic factors, SCL-90-R
      global factor (odds ratio (OR) = 1.87, 95% CI: 1.20-2.91) and subscales factors
      of obsessive compulsiveness (OR = 1.93, 95% CI: 1.31-2.85), interpersonal
      sensitivity (OR = 2.05, 95% CI: 1.09-3.02), depression (OR = 2.09, 95% CI: 1.40
      3.12) and anxiety (OR = 1.58, 95% CI: 1.03-2.44) were still significantly
      associated with an elevated risk of unintentional injury among the retired
      employees. In order to reduce the risk of unintentional injuries among the
      elderly, a psychological health service should be provided in the community.

PMID- 18821381
TI  - Road traffic accidents in Yemen.

PMID- 18821382
TI  - Predictors of goggle use among racquetball players.

PMID- 18821385
TI  - Genistein induces radioprotection by hematopoietic stem cell quiescence.
AB  - PURPOSE: In this study we addressed whether genistein-induced radioprotection in
      mice is associated with alterations of the cell cycle of hematopoietic stem and
      progenitor cells. MATERIALS AND METHODS: C57BL/6J female mice received a single
      subcutaneous injection of genistein (200 mg/kg) 24 h prior to a lethal dose (7.75
      Gy, (60)Co) of total body irradiation. Proliferation-associated Ki-67 protein/7
      aminoactinomycin-D (Ki67/7AAD) cell cycle staining was used to differentiate
      between G(0), G(1), and S/G(2)/M in bone marrow cell populations negative for
      expression of mature hematopoietic lineage marker cells but positive for
      expression of stem cell antigen-1 and tyrosine kinase receptor for stem cell
      factor (Lin(-)Sca-1(+)cKit(+), LSK(+)). Quantitative real-time polymerase chain
      reaction (qRT-PCR) microarrays were utilized to examine cell cycle specific
      genes. RESULTS: At 24 h following radiation exposure, a greater percentage of
      LSK(+) in genistein-treated mice accumulated in the G(0) phase of the cell cycle,
      whereas a large percentage of LSK(+) bone marrow cells from untreated and vehicle
      (PEG-400)-treated mice progressed into the G(1) and S/G(2)/M phases. Moreover,
      the absolute number of marrow total LSK(+), long-term LSK(+), and short-term
      LSK(+) increased 2.8, 12.1, and 4.2-fold, respectively, at 7 days post
      irradiation in genistein-treated vs. untreated irradiated mice. Lin(-) cells from
      genistein-treated mice expressed fewer DNA damage responsive and cell cycle
      checkpoint genes than LSK(+) from untreated or vehicle-treated mice. CONCLUSION:
      Pretreatment with genistein provides in vivo protection from acute myelotoxicity
      through extended quiescence followed by reduced senescence of marrow repopulating
      LSK(+).

PMID- 18821386
TI  - Radiofrequency radiation does not significantly affect ornithine decarboxylase
      activity, proliferation, or caspase-3 activity of fibroblasts in different
      physiological conditions.
AB  - PURPOSE: The aim of this study was to test the hypothesis that variations in the
      physiological state of cells explain inconsistent results from in vitro studies
      on biological effects of radiofrequency (RF) radiation. MATERIALS AND METHODS:
      Murine L929 fibroblasts stimulated with fresh medium, stressed with serum
      deprivation or not subjected to stimulation or stress were exposed in a waveguide
      exposure chamber to 872 MHz continuous wave or pulse modulated (217 pulses per
      second) RF radiation at specific absorption rate of 5 W/kg. Ornithine
      decarboxylase (ODC) activity after 1-and 24-h exposures, proliferation during 48
      h after 24 h exposure, and caspase-3 activity (a measure of apoptosis) after 1 h
      exposure were measured. RESULTS: The cells responded to fresh medium and serum
      deprivation, but no consistent effects of RF radiation were found. One
      statistically significant (p=0.03) RF radiation-related difference was observed
      in ODC activity, but this is most likely a chance finding, as many statistical
      comparisons were performed, and the finding was not supported by any other data.
      CONCLUSIONS: The results did not support effects on the endpoints studied.
      Furthermore, stressed and stimulated cells were not more sensitive than normal
      cells to possible RF radiation-induced effects.

PMID- 18821387
TI  - Molecular responses of Jurkat T-cells to 1763 MHz radiofrequency radiation.
AB  - PURPOSE: The biological effects of exposure to mobile phone emitted
      radiofrequency (RF) radiation are the subject of intense study, yet the
      hypothesis that RF exposure is a potential health hazard remains controversial.
      In this paper, we monitored cellular and molecular changes in Jurkat human T
      lymphoma cells after irradiating with 1763 MHz RF radiation to understand the
      effect on RF radiation in immune cells. MATERIALS AND METHODS: Jurkat T-cells
      were exposed to RF radiation to assess the effects on cell proliferation, cell
      cycle progression, DNA damage and gene expression. Jurkat cells were exposed to
      1763 MHz RF radiation at 10 W/kg specific absorption rate (SAR) and compared to
      sham exposed cells. RESULTS: RF exposure did not produce significant changes in
      cell numbers, cell cycle distributions, or levels of DNA damage. In genome-wide
      analysis of gene expressions, there were no genes changed more than two-fold upon
      RF-radiation while ten genes change to 1.3 approximately 1.8-fold. Among ten
      genes, two cytokine receptor genes such as chemokine (C-X-C motif) receptor 3
      (CXCR3) and interleukin 1 receptor, type II (IL1R2) were down-regulated upon RF
      radiation, but they were not directly related to cell proliferation or DNA damage
      responses. CONCLUSION: These results indicate that the alterations in cell
      proliferation, cell cycle progression, DNA integrity or global gene expression
      was not detected upon 1763 MHz RF radiation under 10 W/kg SAR for 24 h to Jurkat
      T cells.

PMID- 18821388
TI  - Pre-exposure to 50 Hz magnetic fields modifies menadione-induced DNA damage
      response in murine L929 cells.
AB  - PURPOSE: Effects on DNA damage response were investigated in murine L929 cells
      exposed to 50 Hz magnetic fields (MF) with or without ultraviolet B (UVB,
      wavelength 280-320 nm) radiation or menadione (MQ). MATERIALS AND METHODS: Cells
      were exposed to MF at 100 or 300 microT combined with MQ (150 microM, 1 hour) or
      UVB radiation (160 J/m(2)) using various exposure schedules. The samples were
      stained with propidium iodide (PI) and analysed by flow cytometer for cell cycle
      stages. Apoptotic cells were defined as sub G(1) events. RESULTS: In cells first
      exposed to 100 microT MF for 24 h, the response to subsequent MQ treatment was
      significantly altered so that the proportion of sub G(1) cells was decreased and
      the proportion of cells in the G(2)/M phase was increased. When a 300 microT MF
      was used, also the proportion of cells in the G(1) phase was decreased. MF
      exposures after MQ treatment did not alter responses to MQ. No effects were found
      from MF exposure alone or from MF combined with UVB radiation. CONCLUSIONS: The
      results strengthen previous findings suggesting that pre-exposure to MF can alter
      cellular responses to other agents, and indicate that MF as low as 100 microT has
      measurable impacts on cancer-relevant cellular processes such as DNA-damage.

PMID- 18821389
TI  - The expression and intranuclear distribution of nucleolin in HL-60 and K-562
      cells after repeated, short-term exposition to rotating magnetic fields.
AB  - PURPOSE: The aim of the study was to analyze the influence of rotating magnetic
      fields (RMF) on the expression and intranuclear distribution of nucleolin,
      protein involved in ribosome biosynthesis, in HL-60 (acute promyelocytic
      leukemia) and K-562 (chronic myelogenous leukemia) established human cell lines.
      MATERIALS AND METHODS: Cells were exposed to RMF for two chosen states of the
      magnetic field induction: B=10 mT and B=20 mT in experimental set-up for 30 min
      with 24-h intervals for four days. Cytospin slides were prepared and expression
      of nucleolin was detected using monoclonal antibodies. Parameters of fluorescence
      related to nucleolin were measured in at least 2000 tumor cells in each slide by
      a laser scanning cytometer with an argon laser. Percentages of cells in different
      phases of cell cycle were also analyzed. RESULTS: The repeated exposition of
      cells to RMF caused significant increase in nucleolin expression in the whole
      nucleus and in the nucleolin aggregates (NUA). The redistribution of nucleolin
      measured by changes in number of NUA was also observed. The exposition of both
      cell lines studied to RMF did not alter the cell cycle. CONCLUSION: The nucleolin
      is responsive to RMF in HL-60 and K-562. The increase of its expression may
      indicate a reaction of cells to RMF and it may influence their other biological
      properties.

PMID- 18821390
TI  - Exacerbation of autoimmune thyroiditis by a single low dose of whole-body
      irradiation in non-obese diabetic-H2h4 mice.
AB  - PURPOSE: To evaluate how irradiation affects thyroid autoimmunity in mouse models
      of Hashimoto's thyroiditis and Graves' hyperthyroidism. MATERIALS AND METHODS:
      Non-obese diabetic (NOD)-H2(h4) mice spontaneously develop anti-thyroglobulin
      (Tg) antibodies and thyroiditis when supplied with sodium iodine (NaI) in the
      drinking water. BALB/c mice develop anti-thyrotropin receptor (TSHR) antibodies
      and hyperthyroidism following immunization with adenovirus expressing TSHR (Ad
      TSHR). Mice were irradiated as follows: A single whole-body irradiation with
      0.05, 0.5 or 3 Gy one week before or after the beginning of NaI or immunization
      with Ad-TSHR, fractionated whole-body irradiations with 0.05 Gy twice a week or
      0.5 Gy once a week from one week before NaI or Ad-TSHR immunization, or a single
      regional irradiation to the thyroid gland with 0.5 Gy one week before NaI. The
      effect of a single irradiation with 0.05, 0.5 or 3 Gy on splenocytes was also
      evaluated. RESULTS: A single whole-body irradiation with 0.5 Gy one week before
      NaI exacerbated thyroiditis and increased anti-Tg antibody titers in NOD-H2(h4)
      mice. In contrast, any irradiation protocols employed did not affect incidence of
      hyperthyroidism or anti-TSHR antibody titers in BALB/c mice. High-dose
      irradiation increased the relative ratios of effector T cells to regulatory T
      cells (an indication of enhanced immune status) but kills most of T cells.
      CONCLUSIONS: These results indicate that a single whole-body low-dose irradiation
      with 0.5 Gy exacerbates thyroiditis in NOD-H2(h4) mice, data consistent with some
      clinical evidence for increased incidence of thyroid autoimmunity by
      environmental irradiation.

PMID- 18821391
TI  - S-phase cell-specific modification by gemcitabine of PFGE-analyzed radiation
      induced DNA fragmentation and rejoining.
AB  - PURPOSE: To assess the cell cycle-dependent influence of gemcitabine on ionizing
      radiation-induced DNA double-strand breakage (DSB) and rejoining measured by
      pulsed-field gel electrophoresis (PFGE). MATERIALS AND METHODS: WIDR cells (human
      colon carcinoma) were synchronized by serum starvation/stimulation providing
      populations with 7% (G1) or 50% S-phase cells, respectively. Following drug
      treatment (0.5 microg/ml for 2 hours) cells were irradiated (up to 90 Gy) or
      incubated for repair (up to 6 h after 40 Gy). Cell cycle changes were monitored
      by flow cytometry, DNA fragmentation was assessed by PFGE as fraction of
      electrophoretically mobile DNA. RESULTS: Without drug treatment, irradiated S
      phase cells exhibited lower PFGE signals than the G1 cells due to the well known
      electrophoretic immobility of replicative DNA fragments, but DSB rejoining was
      not different. Gemcitabine pretreatment increased the apparent initial radiation
      induced DNA fragmentation specifically for S-phase cells. This effect was rapidly
      reversed (1 h) during incubation for repair. CONCLUSIONS: The data indicate that
      gemcitabine causes the formation of additional radiation-induced DSB in S-phase
      cells or destabilizes the replicative structures that otherwise prevent DNA
      fragment migration during PFGE. The latter would be rapidly restituted
      superimposing DSB rejoining. This is discussed in relation to the recently
      proposed role of mismatch repair in gemcitabine radiosensitization.

PMID- 18821392
TI  - Characterization of cells expressing RNA polymerase II tagged with green
      fluorescent protein: effect of ionizing irradiation on RNA synthesis.
AB  - PURPOSE: To isolate and to characterize cells expressing RNA polymerase II tagged
      with green fluorescent protein for analyses of the effects of ionizing radiation
      on transcription in living cells. MATERIALS AND METHODS: We introduced an alpha
      amanitin-resistant mutation into a vector encoding the largest subunit of RNA
      polymerase II tagged with green fluorescent protein (GFP-pol). Cell lines stably
      expressing functional GFP-pol were isolated under selection with alpha-amanitin
      from a Chinese hamster cell line, CHO-K1, and a radiation-sensitive mutant CHO
      cell line, XR-1. RESULTS: We tested the functionality of the fusion protein in
      vivo by determining RNA synthesis activity by incorporation of nucleoside
      analogues. Both CHO-K1 and XR-1 cells expressing GFP-pol had properties similar
      to those of their respective parental cell lines, indicating that GFP-pol is
      functional. CONCLUSIONS: These stable lines might prove useful for analyses of
      the roles of transcription after ionizing radiation.

PMID- 18821393
TI  - Nonclinical aspects of biopharmaceutical development: discussion of case studies
      at a PhRMA-FDA workshop.
AB  - Robust assessments of the nonclinical safety profile of biopharmaceuticals are
      best developed on a scientifically justified, case-by-case basis, with
      consideration of the therapeutic molecule, molecular target, and
      differences/similarities between nonclinical species and humans (ICH S6).
      Significant experience has been gained in the 10 years ensuing since publication
      of the ICH S6 guidance. In a PhRMA-FDA-sponsored workshop, "Nonclinical Aspects
      of Biopharmaceutical Development," industry and US regulatory representatives
      engaged in exploration of current scientific and regulatory issues relating to
      the nonclinical development of biopharmaceuticals in order to share scientific
      learning and experience and to work towards establishing consistency in
      application of general principles and approaches. The proceedings and discussions
      of this workshop confirm general alignment of strategy and tactics in development
      of biopharmaceuticals with regard to such areas as species selection, selection
      of high doses in toxicology studies, selection of clinical doses, the conduct of
      developmental and reproductive toxicity (DART) studies, and assessment of
      carcinogenic potential. However, several important aspects, including, for
      example, appropriate use of homologues, nonhuman primates, and/or in vitro models
      in the assessment of risk for potential developmental and carcinogenic effects,
      were identified as requiring further scientific exploration and discussion.

PMID- 18821394
TI  - Legislation and informed consent brochures for dental patients receiving amalgam
      restorations.
AB  - In 2008, Norway banned the use of mercury for amalgam restorations. Four states
      in the United States have developed Informed Consent Brochures for amalgam
      restorations that must be given to their dental patients. The authors describe a
      patient who had a large cavity in his left lower molar tooth no.18 that had to be
      removed by an oral surgeon. When the patient went to the oral surgeon, the
      surgeon told the patient that he would replace the carious tooth with a gold
      implant. He was not given an Informed Consent Brochure regarding dental
      restorative materials. The oral surgeon extracted the carious tooth, replacing
      the tooth with a supposed gold crown implant. On his yearly dental examination,
      his dentist took an x-ray of his dental implant and explained that the x-ray
      could not distinguish whether the implant contained either gold or mercury.
      Consequently, the dentist referred him to a dental clinic in which the dental
      implant could be removed without mercury contamination of the patient's
      neurologic system during the extraction of the implant from the root canal.
      During the removal of the dental restoration, the dentist found build up
      expanding into the root canal that had a black color. The crown and underlying
      tooth were sent to ALT BioScience for analysis. Elemental analysis of the crown
      and underlying tooth confirmed the presence of mercury in the restoration. The
      patient should have been given an Informed Consent Brochure by the dentist that
      described the dental restoration that was used in the dental implant.

PMID- 18821395
TI  - Oral bioavailability of cyclotrimethylenetrinitramine (RDX) from contaminated
      site soils in rats.
AB  - Cyclotrimethylenetrinitramine (RDX), a commonly used military explosive, was
      detected as a contaminant of soil and water at Army facilities and ranges. This
      study was conducted to determine the relative oral bioavailability of RDX in
      contaminated soil and to develop a method to derive bioavailability adjustments
      for risk assessments using rodents. Adult male Sprague-Dawley rats preimplanted
      with femoral artery catheters were dosed orally with gelatin capsules containing
      either pure RDX or an equivalent amount of RDX in contaminated soils from
      Louisiana Army Ammunition Plant (LAAP) (2300 microg/g of soil) or Fort Meade (FM)
      (670 microg/g of soil). After dosing rats, blood samples were collected from
      catheters at 2-h intervals (2, 4, 6, 8, 10, and 12) and at 24 and 48 h. RDX
      levels in the blood were determined by gas chromatography. The results show that
      the peak absorption of RDX in blood was 6 h for neat RDX (1.24 mg/kg) and for RDX
      from contaminated soil (1.24 mg/kg) of LAAP. Rats dosed with RDX-contaminated FM
      soil (0.2 mg/kg) showed peak levels of RDX in blood at 6 h, whereas their
      counterparts that received an identical dose (0.2 mg/kg) of neat RDX showed peak
      absorption at 4 h. The blood levels of absorbed RDX from LAAP soil were about 25%
      less than for neat RDX, whereas the bioavailability of RDX from FM soils was
      about 15% less than that seen in rats treated with neat RDX (0.2 mg/kg). The oral
      bioavailability in rats fed RDX in LAAP soil and the FM soil was reduced with the
      neat compound but decrease in bioavailability varied with the soil type.

PMID- 18821396
TI  - Contamination with depleted or enriched uranium differently affects
      steroidogenesis metabolism in rat.
AB  - Uranium is a naturally occurring heavy metal found in the Earth's crust. It is an
      alpha-emitter radioactive element from the actinide group that presents both
      radiotoxicant and chemotoxicant properties. Some studies revealed that uranium
      could affect the reproductive system. To distinguish chemical versus radiological
      effects of uranium on the metabolism of the steroids in the testis, rats were
      contaminated via their drinking water with depleted or enriched uranium. Animals
      were exposed to radionuclides for 9 months at a dose of 40 mg/L (560 Bq/L for
      depleted uranium, 1680 Bq/L for enriched uranium). Whereas depleted uranium did
      not seem to significantly affect the production of testicular steroid hormones in
      rats, enriched uranium significantly increased the level of circulating
      testosterone by 2.5-fold. Enriched uranium contamination led to significant
      increases in the mRNA levels of StAR (Steroidogenic Acute Regulatory protein; 3
      fold, p = .001), cyp11a1 (cytochrome P45011a1; 2.2-fold, p < .001), cyp17a1
      (cytochrome P45017a1; 2.5-fold, p = .014), cyp19a1 (cytochrome P45019a1; 2.3
      fold, p = .021), and 5alpha -R1 (5alpha reductase type 1; 2.0-fold, p = .02),
      whereas depleted uranium contamination induces no changes in the expression of
      these genes. Moreover, expression levels of the nuclear receptors LXR (Liver X
      Receptor) and SF-1 (Steroidogenic Factor 1), as well as the transcription factor
      GATA-4, were modified following enriched uranium contamination. Altogether, these
      results show for the first time a differential effect among depleted or enriched
      uranium contamination on testicular steroidogenesis. It appears that the
      deleterious effects of uranium are mainly due to the radiological activity of the
      compound.

PMID- 18821397
TI  - Safety of intranasally administered archaeal lipid mucosal vaccine adjuvant and
      delivery (AMVAD) vaccine in mice.
AB  - The safety profile of a recently described novel archaeal lipid mucosal vaccine
      adjuvant and delivery (AMVAD) system capable of eliciting robust antigen-specific
      mucosal and systemic immune responses was evaluated in female Balb/c mice
      (10/group) using ovalbumin (OVA) antigen. Mice were intranasally immunized (0, 7,
      and 21 days) with a vaccine comprising 1 microg OVA (0.05 mg/kg body weight)
      formulated in 0.04 mg total polar lipids extract (2.17 mg/kg body weight) of
      Methanobrevibacter smithii constituting the AMVAD system. Control groups were
      similarly immunized with 10-fold higher AMVAD vaccine dose (0.54 mg OVA and 21.7
      mg lipid per kg), saline, 10 microg OVA in saline, or 0.04 or 0.4 mg lipid
      constituting empty AMVAD (no OVA) in saline, or were naive mice. Clinical signs,
      rectal temperature, and body weight were monitored once daily or as appropriate.
      Half the mice in each group were euthanized at 2 days after the first
      immunization. Blood was collected for clinical chemistry analyses. Major organs
      (heart, lungs, kidneys, liver, spleen, thymus, and brain) were examined
      macroscopically and histologically. The remaining mice were euthanized at 29 days
      and blood and organs collected for analyses as done at 2 days. Feces collected at
      27 days, and sera, bile, and nasal lavage at 29 days, were assayed for antibody
      responses. Based on clinical symptoms, temperature, body weight changes, serum
      clinical chemistry, and tissue histopathology, there were no overt toxicities
      associated with OVA/AMVAD or empty AMVAD vaccines. There were no antibodies
      elicited against the lipids comprising the AMVAD system. These results
      demonstrate that at 10-fold excess dose of that required for vaccine efficacy,
      intranasally administered AMVAD vaccine appears to be relatively safe.

PMID- 18821398
TI  - Effects of administration of a monoclonal antibody against mouse tumor necrosis
      factor alpha during pregnancy and lactation on the pre- and postnatal development
      of the mouse immune system.
AB  - Monoclonal antibodies directed against tumor necrosis factor alpha (TNFalpha) are
      currently employed in the treatment of various immune-mediated diseases. These
      studies were designed to evaluate potential effects of anti-TNFalpha treatment in
      mice during pregnancy and lactation on the development of the immune system in
      the F1 generation. Pregnant CD-1 mice were treated with vehicle or with 10 or 40
      mg/kg of an anti-mouse TNFalpha monoclonal antibody (mAb) (cV1q) on days 6, 12,
      and 18 of gestation and on days 3, 9, and 15 of lactation. Evaluation of immune
      system functionality was conducted in F1 generation mice at 11 weeks of age.
      Immune function was evaluated by splenocyte phenotyping, immunoglobulin M (IgM)
      antibody response to sheep red blood cells (SRBCs), spleen cell proliferative
      response to anti-CD3, and natural killer cell activity. Treatment of pregnant
      mice with cV1q produced no adverse effects in the dams and no adverse effects in
      the F1 generation. In general, the functioning of the immune system of the F1
      generation did not appear to be adversely affected following exposure to cV1q in
      utero and during lactation. The only statistically significant change was a
      slight (approximately 20%) reduction in the spleen cell expansion in response to
      SRBC immunization in the female F1 mice from the 40 mg/kg cV1q treatment group.
      In conclusion, administration of a monoclonal antibody against mouse TNFalpha
      during pregnancy and lactation had little or no effect on selected immune
      parameters in mice, with only a possible minor attenuation of spleen cell
      response to immunization noted in the female F1 generation at 11 weeks of age.

PMID- 18821400
TI  - Novel environmental enrichment may provide a tool for rapid assessment of animal
      personality: a case study with giant pandas (Ailuropoda melanoleuca).
AB  - Historically, the assessment of nonhuman animal personality has included a
      variety of methods--from direct behavioral observations in a variety of test
      situations to assessments provided by animal caretakers or trainers. Careful
      observation of how animals in zoos interact with novel enrichment may provide
      reliable insight into their personality. This study sought to describe a process
      for evaluating whether different methods of assessing personality result in
      similar conclusions. The study exposed 4 giant pandas at the Smithsonian National
      Zoological Park and Zoo Atlanta to 10 novel enrichment items and recorded their
      behavior. Keepers also rated each panda on 23 behavioral characteristics on a
      survey. The study obtained individual behavior profiles for each panda.
      Significant differences across individuals in both the novel enrichment trials
      and keeper surveys formed the basis for the profiles. These methods also provided
      some insight into differences between the sexes that--based on the natural
      history of giant pandas--are qualitatively similar to what would be expected. The
      study found some consistency between assessment methods. However, there is a need
      for further study to validate these measures in a larger sample of giant pandas.

PMID- 18821401
TI  - Feeder use patterns in group-housed pregnant sows fed with an unprotected
      electronic sow feeder (Fitmix).
AB  - Previous studies on feeder use in group-housed pregnant sows focused on dynamic
      groups and protected electronic sow feeders (ESF). This study observed 60
      pregnant sows, 1st to 8th parity--housed from Day 29 of pregnancy to 1 week
      before parturition in stable groups of 20 animals, 1 Fitmix feeder per group.
      Data from 25 nonconsecutive 24-hr feeding cycles showed sows making several
      visits to the feeder. Literature on conventional ESF indicated shorter daily
      feeder occupation. Daily feeder occupation per sow decreased over time (p <
      .001). The study observed maximum feeder activity in the hours following the
      start of each feeding cycle. During the experiment, there was a relatively
      stable, quickly established, and maintained feeder order (W > 0.80, p < .001).
      This highly correlated with dominance rank (r(s) = 0.80, p < .001). High-ranking
      sows fed earlier and made as many--but longer--visits as low-ranking sows; thus,
      they occupied the feeder more time every day (p < .01). Although optimization of
      the feeder efficiency may take several weeks, Fitmix seems an efficient feeding
      system for medium-size, stable groups of sows.

PMID- 18821402
TI  - Behavior of lambs in rest pens during long-distance transport.
AB  - The aim of this study was to determine how one group of lambs utilized 2
      consecutive rest periods in novel environments with access to food and water that
      occurred during 22 hr of motor transport. The 18.5 +/- 0.6 kg lambs (n = 15) were
      transported for 8 hr and then unloaded for a 6-hr rest period. After 6 hr, the
      lambs were reloaded for another 8 hr of transport followed by a 24-hr rest
      period. Reloading for a second 8 hr of transport followed the initial rest
      period. The percentage of lambs engaged in drinking, eating, lying, playing, or
      "other" was determined at 15-min intervals. During the 6-hr rest period, peak
      lying behavior occurred during the 2nd and 6th hr of the period. During the first
      6 hr of the 24-hr rest period, the percentage of lambs lying increased while the
      percentage of lambs eating decreased. In addition, the percentage of lambs lying
      during the first 6 hr of the 24-hr rest period was greater than during the 6-hr
      rest period. Lying down had a greater priority than eating during the second (24
      hr) rest period.

PMID- 18821403
TI  - Results of a free spay/neuter program in a Hispanic colonia on the Texas-Mexico
      border.
AB  - The purpose of this study, conducted in a small, impoverished Hispanic community
      on the Texas-Mexico border, was to evaluate the level of participation in a
      bilingual spay/neuter program offered free of charge to residents with companion
      animals. Prior to the sterilization project, approximately 11% of dogs and about
      27% of cats with guardians underwent surgical sterilization. Over an 8-month
      period, the spay/neuter program sterilized about 47% of dogs and 38% of cats who
      had guardians in the community. In spite of residents' early reluctance to neuter
      their dogs, the project sterilized nearly equal numbers of male and female dogs
      (200 male; 201 female).

PMID- 18821404
TI  - Influence of zoo visitor presence on the behavior of captive Indian gaur (Bos
      gaurus gaurus) in a zoological park.
AB  - Visitors to zoos can be a source of potential disturbance and stress to some
      captive, nonhuman animals in the wild. To determine the influence of visitor
      presence on captive bison (Bos gaurus gaurus), the study analyzed the behavior of
      4 individuals at the Arignar Anna Zoological Park, India. The study often
      observed the behavior of the animals on visitor-present days and on days when
      visitors were absent. In the presence of zoo visitors, the bison showed a higher
      level of intragroup aggression and moving behavior. In contrast, the bison rested
      more when no visitors were present. The results revealed that the presence of zoo
      visitors significantly influenced the behavior of captive bison and thereby may
      have affected their welfare.

PMID- 18821405
TI  - Function of tongue-playing of cattle in association with other behavioral and
      physiological characteristics.
AB  - To study the function of tongue-playing of cattle, this study observed 71
      Japanese Black x Holstein steers after feeding in 2 repetitive experiments. The
      number of steers who performed tongue-playing did not differ among the 3 levels
      of environmentally enriched pens. Most (90.6%) performances of tongue-playing
      terminated within 20 min. Frequency of tongue-playing positively correlated with
      the frequency of resting (r = 0.25, p < .05). Frequency of eating was lower in
      tongue-playing steers (n = 40) than in non-tongue-playing steers (n = 31; p <
      .05). Frequencies of self-grooming (p < .05), ruminating (p < .05), and lying
      ruminating (p < .01) were higher in tongue-playing steers. Plasma dopamine
      concentration was lower in tongue-playing steers (p < .05). In conclusion, tongue
      playing that lasts only for a short time after feeding was induced by behavioral
      features of steers who rest more and eat hay less at the same time as they
      perform grooming and ruminating.

PMID- 18821406
TI  - Selection of calibration standard concentrations for determination of intact-PTH
      by immunoradiometric assay.
AB  - The routine determination of parathyroid hormone (PTH) by immunoradiometric assay
      (IRMA) has been studied. Concentrations of standards have been adequate to the
      clinical range in order to reduce errors. Proposed standards were tested by the
      calculation of different quality parameters. Recoveries of sample concentrations
      were estimated for different experimental alterations (methodological errors,
      reagent degradation, or changes in background response). Finally, inter-assays
      demonstrated that reproducibility of samples with concentrations in the critical
      clinical limits was improved. The results confirmed that the proposed selection
      provided a more robust method and it is possible to extrapolate to other clinical
      immunoassays.

PMID- 18821407
TI  - Immunogenic proteins in the cell envelope and cytoplasm of vancomycin-resistant
      enterococci.
AB  - Because of the continuous advent of new modes of antimicrobial resistance, it has
      become difficult to control vancomycin-resistant enterococci (VRE) with standard
      antibiotics. Therefore, in the interest of public health, early diagnostic
      methods and a greater knowledge of the pathogenic process are urgently needed to
      prevent the spread of VRE in humans and animals. To this end, we sought
      immunogenic proteins suitable for the serological diagnosis of VanA-, VanB-,
      VanC1-, and VanC2-type VRE. Proteins were extracted from cell envelope (CE) and
      cytoplasm (CP), and anti-VRE guinea pig serum was used to identify immunogenic
      proteins. Two immunogenic proteins of 129 and 29 kDa were identified in the CE
      and CP of VanA, respectively, while a 28-kDa protein was identified in the CP of
      VanB. Additionally, the CE of VanC1 contained two immunogenic proteins of 30 and
      46 kDa, while the CP of VanC1 contained two proteins of 19 and 30 kDa. The CE of
      VanC2 possessed one immunogenic protein of 40 kDa. These proteins, which were
      specific to individual subtypes of VRE, will likely prove useful in the
      serological diagnosis of enterococcal infections and in the study of enterococcal
      pathogenesis.

PMID- 18821408
TI  - Complexities of clinical assay development and optimization prior to first-in-man
      immunization trials - a description of immunogenicity assay development for the
      testing of samples from a phase 1 Alzheimer's vaccine trial.
AB  - Immunogenicity is often a critical clinical endpoint in the assessment of
      vaccines prior to the submission of data to regulatory agencies. As a result, the
      assays used to measure immunogenicity must be highly characterized, well
      controlled, and statistically supported. These goals are not easily attained,
      however, when the development of the assay must occur prior to the first-in-man
      studies. Two significant barriers exist in the development of these assays: (1)
      the lack of experience with the performance of a novel antigen in a clinical
      assay, and (2) the lack of available proper human clinical samples to create
      reference standards and assess sample matrices. To help to overcome these
      obstacles, we employed a screening experimental design to assess assay
      optimization. Design of experiments (DOE) is a statistical tool that allows for
      the evaluation of all of the key assay parameters to determine the optimal
      conditions for the assay, as well as determine if there are any interactions of
      these parameters on the response of the assay. The multivariate approach that is
      integral to DOE helps to overcome the lack of experience with the assay reagents
      by facilitating an understanding of how the variables work together in the
      performance of the assay. Here, we outline the use of full and fractional
      factorial DOE in the optimization of a clinical assay on two platforms, Luminex
      and ELISA, for the measurement of antibodies to the beta-amyloid peptide (Abeta)
      for a novel first-in-man vaccine program. Both platforms are evaluated in an
      attempt to determine the assay best suited to the needs of the program. We also
      describe the specificity experiments performed to further characterize the
      utility of each assay platform.

PMID- 18821409
TI  - Determination of (+)-3,3',5,5'-Tetraiodo-L-thyronine (L-T4) in Serum and
      pharmaceutical formulations using a sequential injection analysis/immunosensor
      system.
AB  - A sequential injection analysis/immunosensor system is proposed for the analysis
      of thyroxine (L-T4) in serum and in pharmaceutical formulations with a rate of 75
      samples/hour. The immunosensor design is based on the physical immobilization of
      anti-L-T4 in carbon paste. The working concentration range of the immunosensor in
      the sequential injection analysis system is between 36 and 1080 ng/mL with a
      limit of detection of 24.6 ng/mL. The system is very reliable and very easy to
      design and operate.

PMID- 18821410
TI  - Development of fluorescence polarization immunoassay for the detection of
      organophosphorus pesticides parathion and azinphos-methyl.
AB  - Organophosphorus Pesticides (OPPs) are a group of artificially synthesized
      substances used in farms to control pests and to enhance agricultural production.
      Although these compounds show preferential toxicity to insects, they are also
      toxic to humans and mammals by the same mode of action. ELISA now is an
      alternative method to detect OPPs. But, it must bear heterogenous properties,
      since several separation steps are needed during the ELISA method protocols. The
      FPIAs, which belong to homogenous assay, for determination of OPPs parathion and
      zainphos-methyl have been developed. The characteristics of Dep-EDF and PM-B-EDF
      tracers binding with antibodies A and D were investigated in the antibodies
      dilution experiments. The PM-B-EDF tracer combination with antibody D was
      selected to construct the standard curve for parathion detection. The IC50 value
      and the detection of limit were 1.96 mg/L and 0.179 mg/L, respectively, as shown
      in the standard curve. The tracers of PBM-EDF 2 and 3, which were chased from 4
      PBM-EDF tracers, exhibited the good standard curves based on the MAb AZI-110. The
      FPIA constructed to analyze the azinphos-methyl showed the IC50 1.003 mg/L and
      detection limit 0.955 mg/L when PBM-EDF 2 was employed and the IC50 0.1487 mg/L
      and detection limit 0.150 mg/L were obtained when PBM-EDF 3 was used.

PMID- 18821411
TI  - Viability and function in lymphocytes cultured from the horse, chicken, and
      mouse: effects of different leukocyte enrichment techniques.
AB  - Methods of lymphocyte enrichment tend to vary across species, with the most
      common techniques employed being density-gradient separation and erythrocyte
      lysis buffer enrichment. In this study, we assessed lymphocyte viability and
      proliferation of avian, equine, and murine lymphocytes enriched by a commercial
      density-gradient technique and under identical, standardized culture conditions.
      The results of this study clearly show that, under identical enrichment and
      culture conditions, lymphocyte viability and function can be quite different
      among the equine, bird, and mouse species. Secondly, the type of enrichment
      technique employed in the mouse can impact the quality of the immune data
      generated.

PMID- 18821412
TI  - A novel enzyme-linked immunosorbent assay for cortisol using a long-chain
      biotinylated cortisol-3-CMO derivative.
AB  - An enzyme-linked immunosorbent assay (ELISA) using streptavidin-biotin system as
      a bridge between antibodies bound antigen and reporter molecule (horseradish
      peroxidase enzyme) has been described. The cortisol antiserum was generated
      against cortisol-3-O-carboxylmethyl oxime-bovine serum albumin (F-3-CMO-BSA). We
      have prepared biotin-labelled cortisol as a primary probe and utilized
      streptavidin-labelled horseradish peroxidase (SA-HRP) as secondary probe to
      monitor the antigen-antibody interaction. To the cortisol antibody coated micro
      wells, 25 microL of standard or samples, along with 100 microL of biotinylated
      cortisol, were kept for 1 h at room temperature. Thereafter, wells were washed
      and 100 microL of SA-HRP was added to all wells and kept again for 20 min at room
      temperature. Bound enzyme activity was measured using tetramethyl
      benzidine/hydrogen peroxidase (TMB/H2O2) as substrate. The incorporation of
      streptavidin-biotin system as a bridge between antibody bound antigen and
      reporter molecule (horseradish peroxidase enzyme) increased sensitivity and
      specificity of the cortisol assay. The use of low molecular weight primary label
      (F-3-CMO-biotin) might have facilitated the easy and selective access of the
      analyte present in serum to compete with the antigen-binding pocket of antibody,
      thereby detecting as low as 3.42 ng/mL of analyte specifically.

PMID- 18821413
TI  - Localized heating characteristics of hyperthermia using a reentrant cavity.
AB  - An applicator based on a reentrant cavity with excellent localized heating
      characteristics is proposed in order to treat deep tumours localized in the head
      and neck. Numerical and experimental analyses of the applicator, which produces
      an electromagnetic field distribution required for this type of localized
      heating, are performed. A simple and clear procedure for achieving localized
      heating requires applicator miniaturization. However, miniaturization causes an
      increase in the resonant frequency and leads to the degradation of the
      characteristics for heating deep tissue. Therefore, it is proposed that
      dielectrics be inserted into the applicator and the resonant frequency be
      reduced. From the results of the numerical analysis and experimental examination,
      it is shown that a deep region of 100-120 mm around the centre of a phantom can
      be heated.

PMID- 18821414
TI  - Effect of postural changes on lower limb blood volume, detected with non-invasive
      photoplethysmography.
AB  - This paper describes the effect of passive leg raising on blood volume change in
      the lower limb, using a dual probe photoplethysmography (PPG) system employing a
      tissue optics model. The normalized AC/DC ratio and DC value are introduced from
      the model to evaluate the dynamic pulsation and total blood volume changes due to
      postural effects. The AC and DC components of PPG signals were collected from a
      passive leg raising protocol. With the leg raised, the normalized AC/DC ratio
      significantly decreased when supine, while the normalized DC value increased
      significantly in both supine and reclining positions. The parameters from the
      stationary leg showed similar but smaller responses. These results demonstrate a
      local and systemic physiological phenomenon in the lower limb blood volume change
      caused by postural changes. The normalized AC/DC ratio and DC value derived from
      the tissue optics model could be applied to assess the blood volume change.

PMID- 18821415
TI  - A multi-channel stimulator and electrode array providing a rotating current
      whirlpool for electrical stimulation of wounds.
AB  - When electrical stimulation is used on wounds, the electrical current has
      difficulty penetrating areas where there is necrotic tissue. Further, for an
      irregularly shaped wound, current distribution is poor in some areas of the wound
      since conventional two-electrode delivery systems provide the greatest current in
      a line directly between the electrodes. A new stimulator and electrode system is
      described which uses three electrodes spaced around a wound to disperse current
      more evenly. The stimulator senses tissue impedance and then redirects current by
      altering its Thevenin's output impedance for each electrode; each of the three
      electrodes becomes the active one in sequence while the remaining are the sink
      electrodes. Eight subjects were examined to test the stimulator. Electrical
      stimulation was applied to the skin above the quadriceps muscle at currents of 15
      mA in six subjects without wounds and in two subjects with wounds. The
      relationship between electrode position and current dispersion on the skin was
      examined with a two-electrode vs. a three-electrode system to set stimulation
      parameters for the computer. The results showed that the three-electrode system
      could (1) detect areas of the skin with high impedance; (2) compensate by
      altering the Thevenin's output impedance at each of the three electrodes to shift
      current to high impedance areas; (3) provide uniform current across the skin as
      assessed by skin current and blood flow measurements with a laser Doppler flow
      imager.

PMID- 18821416
TI  - Numerical simulation of unsteady generalized Newtonian blood flow through
      differently shaped distensible arterial stenoses.
AB  - An updated numerical simulation of unsteady generalized Newtonian blood flow
      through differently shaped distensible arterial stenoses is developed. A shear
      thinning fluid modelling the deformation dependent viscosity of blood is
      considered for the characterization of generalized Newtonian behaviour of blood.
      The arterial model is treated as two-dimensional and axisymmetric with an outline
      of the stenosis obtained from a three-dimensional casting of a mildly stenosed
      artery. The full Navier-Stokes equations governing blood flow are written in the
      dimensionless form and the solution is accomplished by finite time-step
      advancement through their finite difference staggered grid representations. The
      marker and cell (MAC) method comprising the use of a set of marker particles
      moving with the fluid is used for the purpose. Results are obtained for three
      differently shaped stenoses - irregular, smooth and cosine curve representations.
      The present results do agree well with those of existing investigations in the
      steady state, but contrary to their conclusions the present findings demonstrate
      that the excess pressure drop across the cosine and the smooth stenoses is caused
      by neither their smoothness nor their higher degree of symmetry relative to the
      irregular stenosis, but is rather an effect of area cover with respect to the
      irregular stenosis. This effect clearly prevails throughout the entire
      physiological range of Reynolds numbers. Further the in-depth study in flow
      patterns reveals the development of flow separation zones in the diverging part
      of the stenosis towards the arterial wall, and they are influenced by non
      Newtonian blood rheology, distensibility of the wall and flow unsteadiness in
      order to validate the applicability of the present model.

PMID- 18821417
TI  - Effects of noise and filtering on SVD-based morphological parameters of the T
      wave in the ECG.
AB  - Singular value decomposition (SVD) based electrocardiogram (ECG) morphology
      analysis is a novel method in the assessment of subtle abnormalities in the T
      wave morphology of 12-lead ECG. As various types of noise contaminate the ECG
      signal and create a bias for the morphological analyses, this study was designed
      to estimate the effects of noise on the SVD method in an experimental setup.
      Ideal signals were generated by filtering real ECG signals several times with the
      Savitzky-Golay filter. Random and real noise samples were superimposed on the
      ideal signals. The noisy signals were filtered with a power line interference
      filter combined with the Savitzky-Golay or the wavelet filter. Results show that
      noise increased both the dipolar and non-dipolar components significantly unless
      filtering was applied. R-TWR (relative T wave residuum) and A-TWR (absolute T
      wave residuum) were four to eight times higher in noisy signals. The experiments
      with patient data demonstrated that certain types of noise may even lead to
      erroneous classification of patients. Filtering brings the median values closer
      to the correct ones and decreases significantly the variance of the values of
      parameters.

PMID- 18821418
TI  - Comparison of active contour models for image segmentation in X-ray coronary
      angiogram images.
AB  - Snakes, or active contours, are used extensively in computer vision and image
      processing applications, particularly to locate object boundaries. However, most
      present snake models cannot provide better capture range and evolution stop
      mechanism. This project presents a new external force for active contours,
      largely solving both problems. An extension of the gradient vector flow snake
      (GVF snake) method is presented. First, the adaptive balloon force has been
      developed to increase the GVF snake's capture range and convergence speed. Then,
      a dynamic GVF force is introduced to provide an efficient evolution-stop
      mechanism. In this way, we prevent the snake from breaking through the correct
      surface and locking to other salient feature points. The active contour models
      have been applied on X-ray coronary angiogram images. The segmentation results
      demonstrate the potential of improved GVF method is comparison with all previous
      active contour methods. Texture parameters have been calculated and results are
      compared with all active contour models.

PMID- 18821421
TI  - Role of exhaled breath biomarkers in environmental health science.
AB  - As a discipline of public health, environmental health science is the study of
      the linkage from environmental pollution sources to eventual adverse health
      outcome. This progression may be divided into two components, (1) "exposure
      assessment," which deals with the source terms, environmental transport, human
      exposure routes, and internal dose, and (2) "health effects," which deals with
      metabolism, cell damage, DNA changes, pathology, and onset of disease. The
      primary goal of understanding the linkage from source to health outcome is to
      provide the most effective and efficient environmental intervention methods to
      reduce health risk to the population. Biomarker measurements address an
      individual response to a common external environmental stressor. Biomarkers are
      substances within an individual and are subdivided into chemical markers,
      exogenous metabolites, endogenous response chemicals, and complex adducts (e.g.,
      proteins, DNA). Standard biomarker measurements are performed in blood, urine, or
      other biological media such as adipose tissue and lavage fluid. In general,
      sample collection is invasive, requires medical personnel and a controlled
      environment, and generates infectious waste. Exploiting exhaled breath as an
      alternative or supplement to established biomarker measurements is attractive
      primarily because it allows a simpler collection procedure in the field for
      numerous individuals. Furthermore, because breath is a gas-phase matrix, volatile
      biomarkers become more readily accessible to analysis. This article describes
      successful environmental health applications of exhaled breath and proposes
      future research directions from the perspective of U.S. Environmental Protection
      Agency (EPA) human exposure research.

PMID- 18821422
TI  - A review of the immunotoxicity of the pesticide 3,4-dichloropropionanalide.
AB  - The pesticide 3,4-dichloropropionanilide (propanil or, alternatively, DCPA) is a
      member of the acetanilide chemical family and is predominantly used for the
      control of weeds on commercial rice crops worldwide. This article was written to
      provide a brief review of the general toxicity of propanil followed by a detailed
      summary of the immunotoxicity studies that were performed to date in mammalian in
      vivo and in vitro models. Propanil affects the immune system at organ, cellular,
      and molecular levels. Studies demonstrated that it produces thymic atrophy and
      splenomegaly and decreases developing T- and B-cell populations in the thymus and
      bone marrow. Natural killer (NK) cells and macrophages are critical components of
      the innate immune system. NK cell cytotoxicity and the ability of macrophages to
      phagocytose, kill pathogenic bacteria, and produce inflammatory cytokines are
      suppressed by propanil. Propanil also affects the respiratory burst of
      macrophages, inhibiting reactive oxygen and nitrogen species production.
      Molecular mechanisms responsible for propanil's effects have begun to be
      elucidated and include alterations in nuclear factor (NF)-kappaB transcription
      factor activity and intracellular Ca(2+) signaling. Propanil exposure alters a
      number of functions of mature T lymphocytes and B lymphocytes that impacts the
      adaptive immune response. T-cell cytotoxic activity and cytokine production are
      major T-cell functions inhibited by propanil. The humoral antibody response to
      model antigens and intact bacteria is differentially affected after propanil
      exposure. How these changes in innate and adaptive immune responses impact the
      host response to bacterial challenge or vaccination has begun to be examined.

PMID- 18821423
TI  - Human biomonitoring and the INSPIRE directive: spatial data as link for
      environment and health research.
AB  - Recently, there has been a rapid gain of interest in the availability,
      applicability, and integration of different types of spatial data for environment
      and health issues. The INSPIRE Directive (Directive 2007/2/EC) aims at providing
      better and easily accessible spatial information in Europe for the formulation
      and implementation of community policy on the environment by triggering the
      creation of a European spatial information infrastructure that delivers
      integrated spatial information services to potential users. Human biomonitoring
      (HBM) significantly contributes to the already existing data on environment and
      health because of its specific nature of providing information on the internal
      dose of chemicals rather than their mere presence in different environmental
      compartments. However, due to the intrinsic nature of HBM data, a number of
      issues need to be dealt with if HBM data are to be used to its full capacity in a
      geographic information systems (GIS) environment and within the INSPIRE
      directive. The current article highlights some of these issues, and discusses a
      number of options to improve the geographical relevance of HBM data for their
      optimal use within the INSPIRE Directive framework. The main aim of this
      publication is to illustrate that HBM has a significant contribution to make to
      the INSPIRE Directive, although some kind of data aggregation will be necessary
      to protect individual privacy. If HBM data wants to have a significant
      contribution to spatial information used to assist policymaking and on the
      surveillance or tracking of the direct or indirect impact of such policies, the
      HBM data need to be compatible with other data collected within the other themes
      of the INSPIRE Directive.

PMID- 18821424
TI  - Potential for early-life immune insult including developmental immunotoxicity in
      autism and autism spectrum disorders: focus on critical windows of immune
      vulnerability.
AB  - Early-life immune insults (ELII) including xenobiotic-induced developmental
      immunotoxicity (DIT) are important factors in childhood and adult chronic
      diseases. However, prenatal and perinatal environmentally induced immune
      alterations have yet to be considered in depth in the context of autism and
      autism spectrum disorders (ASDs). Numerous factors produce early-life-induced
      immune dysfunction in offspring, including exposure to xenobiotics, maternal
      infections, and other prenatal-neonatal stressors. Early life sensitivity to
      ELII, including DIT, results from the heightened vulnerability of the developing
      immune system to disruption and the serious nature of the adverse outcomes
      arising after disruption of one-time immune maturational events. The resulting
      health risks extend beyond infectious diseases, cancer, allergy, and autoimmunity
      to include pathologies of the neurological, reproductive, and endocrine systems.
      Because these changes may include misregulation of resident inflammatory
      myelomonocytic cells in tissues such as the brain, they are a potential concern
      in cases of prenatal-neonatal brain pathologies and neurobehavioral deficits.
      Autism and ASDs are chronic developmental neurobehavioral disorders that are on
      the rise in the United States with prenatal and perinatal environmental factors
      suspected as contributors to this increase. Evidence for an association between
      environmentally associated childhood immune dysfunction and ASDs suggests that
      ELII and DIT may contribute to these conditions. However, it is not known if this
      linkage is directly associated with the brain pathologies or represents a
      separate (or secondary) outcome. This review considers the known features of ELII
      and DIT and how they may provide important clues to prenatal brain inflammation
      and the risk of autism and ASDs.

PMID- 18821425
TI  - Re: Guyton, Kathryn Z., Barone, Stanley, Jr., Brown, Rebecca C., Euling, Susan
      Y., Jinot, Jennifer, Makris, Susan (2008). Mode of action frameworks: a critical
      analysis. Journal of Toxicology and Environmental Health, Part B, 11(1): 16-31.

PMID- 18821427
TI  - Sixth International Workshop on non-Hodgkin Lymphoma: 16-17 November 2007,
      Boston, USA.
AB  - The sixth annual International Workshop on NHL (iwNHL) meeting began with an
      introduction and welcome by iwNHL Chair, Dr Myron S. Czuczman, Head, Lymphoma and
      Myeloma Service and Lymphoma Translational Research Laboratory at Roswell Park
      Cancer Institute, Buffalo, NY, on behalf of the Scientific Advisory Committee, to
      corporate sponsors, speakers and attendees.

PMID- 18821428
TI  - Treatment of follicular lymphoma: current status.
AB  - With the recent proliferation of treatment options for patients with follicular
      lymphoma (FL), median survival has been shown to have improved, from 84 months
      between 1983 and 1989 to 93 months between 1993 and 1999. Nevertheless, relapse
      is common in this patient group, and treatment options that extend the duration
      of remission without increased toxicity are still required. Rituximab has made a
      major contribution to the treatment of patients with FL, improving outcomes and
      making new treatment schedules possible. It is now a standard practice to
      administer rituximab with first-line combination chemotherapy in patients with
      FL. In addition, a number of current trials are examining the potential role of
      rituximab maintenance therapy in improving outcomes in FL. However, at present it
      is not clear which schedules or combinations are the most effective, and further
      randomised controlled trials of treatment strategies incorporating rituximab are
      needed to provide the evidence that will allow clinicians to maximise the
      potential of this drug. Second-line options for the treatment of FL include
      allogeneic stem cell transplantation, radioimmunotherapy targeted to CD20 and, in
      selected patients, autologous stem cell transplantation. New treatment approaches
      for FL currently being investigated in the second-line setting include the
      proteasome inhibitor, bortezomib and novel anti-CD20 monoclonal antibodies.

PMID- 18821429
TI  - Refining the treatment of follicular lymphoma.
AB  - Many effective treatments are currently available for patients with follicular
      lymphoma (FL). However, given the heterogeneity of this disease, identifying the
      most beneficial treatment for an individual patient remains a challenge, although
      clinical, genetic and biological features can all potentially be used to refine
      therapies in individual cases. The Follicular Lymphoma international prognostic
      index (FLIPI) algorithm is a valuable prognostic tool for risk categorisation.
      Despite its current limitations, further investigation will help to develop the
      role of FLIPI in treatment decision-making, and will increase its value in
      identifying the optimal therapy for individuals. Biological factors such as bulky
      disease, over-expression of Bcl-2, or histological grade can help to identify
      patients at high risk of relapse, and distinguish between the benefits of early
      intervention vs. a watch-and-wait policy in early-stage FL. The tumor
      microenvironment plays an important role in the development of FL, and
      identification of biological and genetic markers could help clinicians determine
      the prognosis of individual patients. Although much work remains to be done, a
      greater understanding of the biology of FL will lead to the development of novel
      therapeutic targets and therapies, bringing individualised treatment a step
      closer.

PMID- 18821430
TI  - Current understanding of the role of Epstein-Barr virus in lymphomagenesis and
      therapeutic approaches to EBV-associated lymphomas.
AB  - A heterogeneous group of malignancies are associated with Epstein-Barr virus
      (EBV) infection. These malignancies arise in both immunosuppressed and
      immunocompetent individuals and can be divided into three patterns of latency
      depending on the viral genes that are expressed. In Type III latency
      malignancies, such as post-transplant lymphoproliferative disorder (PTLD), EBV
      has a direct role and the activated B-cell phenotype is characterised by high
      level expression of all the immunodominant EBV latency proteins. Thus, EBV
      infected B cells are good targets for EBV-specific cytotoxic T lymphocytes
      (CTLs). New immune-based treatments for PTLD include transfer of ex vivo
      generated autologous EBV-specific CTLs or, in the case of bone marrow transplant
      recipients, donor-derived EBV-specific T cells. This strategy could, perhaps,
      also work in Type II latency malignancies, where EBV acts like a cofactor rather
      than having a direct role. In initial studies, T cells specific for the weakly
      immunogenic latent membrane protein 2 have been expanded ex vivo and have
      promoted tumor regression in a subset of patients. Another potential therapeutic
      strategy could be to try to induce lytic EBV infection in the tumor cells. This
      could be done by targeting genes that switch the EBV-infected B cells from the
      latent to the lytic cycle.

PMID- 18821431
TI  - Epidemiology, pathology and treatment of non-follicular indolent lymphomas.
AB  - Non-follicular indolent subtypes of non-Hodgkin lymphoma (NHL), which include
      chronic lymphocytic leukemia, small lymphocytic lymphoma (SLL) and marginal zone
      lymphomas (MZL), are a diverse group of disorders with different presenting
      features, behaviour patterns and treatment outcomes. Current knowledge of these
      subtypes is largely based on retrospective analyses. A precise diagnosis can be
      difficult to achieve, and specific diagnostic criteria are needed to more
      precisely define some of the rarer indolent tumors, such as nodal and splenic
      MZLs. Although some subtypes of NHL have a prolonged indolent course, with a good
      prognosis (e.g. SLL), others (e.g. nodal and splenic MZLs) can rapidly evolve
      into more aggressive subtypes. In asymptomatic patients, treatment may be
      deferred until the disease progresses and the patient becomes symptomatic.
      Universally accepted therapeutic guidelines do not exist, however, and carefully
      designed, prospective clinical studies are needed to further assess optimal
      therapeutic approaches for these indolent NHLs.

PMID- 18821432
TI  - Primary lymphoma of the central nervous system: epidemiology, pathology and
      current approaches to diagnosis, prognosis and treatment.
AB  - An overview of the current approaches to the management of patients with primary
      central nervous system lymphoma (PCNSL) is provided. Although accumulating
      evidence demonstrates that PCNSL is a curable type of brain tumor, in many cases
      establishing the diagnosis and overcoming chemotherapeutic resistance remain
      significant obstacles. The issue of treatment-related neurotoxicity is also a
      central consideration in treatment planning. The introduction of highly active
      antiretroviral therapy has had a major impact on this disease in that the
      incidence of AIDS-related central nervous system lymphoma, once highly prevalent
      in the 1980s and 1990s, has now virtually disappeared. However, the problem of
      diagnostic delays secondary to steroid effects, radiation-induced neurotoxicity
      and methotrexate resistance represent unique and important problems in this
      disease. The use of anti-CD20 antibody in this disease represents the first
      application of biologically based targeted therapies for PCNSL; however, the
      overall impact of this modality in brain lymphoma awaits further evaluation in
      ongoing studies The application of proteomic as well as gene expression
      technologies is yielding insights into PCNSL pathogenesis, in particular specific
      oncogenic pathways, which may be exploited to develop new therapies.

PMID- 18821433
TI  - Secondary lymphomas of the central nervous system: risk, prophylaxis and
      treatment.
AB  - The recurrence of non-Hodgkin lymphoma (NHL) in the central nervous system (CNS)
      is rapidly fatal in most cases. Highly aggressive lymphomas, such as
      lymphoblastic and Burkitt lymphomas, carry a high risk of CNS relapse. CNS
      relapse in intermediately aggressive subtypes, such as diffuse large B-cell
      lymphoma, is uncommon, but not rare. The risk of CNS relapse in indolent
      lymphomas is low. Prognostic markers of CNS relapse include elevated serum
      lactate dehydrogenase levels, the presence of B symptoms, and extranodal
      involvement at more than one site. Most centers give prophylactic CNS
      chemotherapy to patients considered at high risk of CNS recurrence. However,
      definitions of risk factors vary, and there is a lack of consensus regarding
      prophylaxis indications. More research is needed to define which patients might
      benefit from CNS prophylaxis at initial treatment and to find the optimal regimen
      for prophylaxis. A variety of treatments have been used to treat CNS relapse, but
      current regimens have had little success in extending survival after CNS relapse.
      Although long-term survival has been reported in a minority of patients with
      isolated CNS recurrence after treatment with methotrexate, more effective
      regimens are needed if survival times after relapse are to be prolonged.

PMID- 18821434
TI  - Novel approaches for the treatment of NHL: Proteasome inhibition and immune
      modulation.
AB  - Proteasome inhibitors and immunomodulatory drugs (IMiDs) have demonstrated
      clinical potential as novel therapies for non-Hodgkin lymphoma (NHL). Bortezomib,
      a peptide aldehyde derivative that inhibits the proteasome by binding directly to
      its active sites, is the most extensively studied agent in the clinical setting.
      Single-agent bortezomib is effective in several lymphoid malignancies, and is
      recommended for second-line treatment of mantle-cell lymphoma (MCL). Ongoing
      trials are investigating the combination of bortezomib with chemotherapy, and
      with agents that target Bcl-2 proteins. Although proteasome inhibitors are
      potentially potent anti-tumor drugs, the pleotropic nature of their biological
      effects means that further research is required to elucidate the optimal
      combinations, doses and schedules. In addition to proteasome inhibitors, the
      IMiDs, such as lenalidomide, have the potential to improve outcomes for patients
      with NHL. These drugs inhibit cell growth and proliferation by several
      mechanisms, including blocking the effect of growth factors and stimulating T
      cells and natural killer cells. Lenalidomide is particularly effective in
      lymphoproliferative disorders such as multiple myeloma, and is active in patients
      with various forms of NHL, with a favourable side-effect profile. Complimentary
      clinical and pharmacological features suggest that lenalidomide may be effective
      when combined with monoclonal antibodies. Ongoing and future studies will provide
      further information.

PMID- 18821438
TI  - Effects of 5-Form, Yang Style Tai Chi on older females who have or are at risk
      for developing osteoporosis.
AB  - This study investigated the effects of 5-Form, Yang Style Tai Chi (TC) on balance
      confidence, balance performance, functional strength, mobility, and incidence of
      falls among individuals with or at risk for developing osteoporosis. This was a
      pilot outcomes study in which participants served as their own controls. Thirty
      one independent, community-dwelling women (mean age of 67.3 years) attended TC
      sessions twice a week for 12 weeks and practiced at least 1 day a week on their
      own. A specific TC instruction video was used to facilitate home practice.
      Baseline, immediate postintervention, and 6 and 12 months postintervention data
      were recorded. Outcome measures included the Activities-specific Balance
      Confidence (ABC) Scale, One-Legged Stance Test (OLST) for both legs, Repeated
      Chair Stands (RCS), and the Timed Up and Go Test (TUG). Exercise performance and
      falls were tracked during the study by using daily diaries. Balance performance,
      functional strength, and mobility significantly improved (p < 0.05) immediately
      postintervention. Most benefits were sustained at 6 months, but only functional
      strength and mobility remained improved at 12 months postintervention. Most
      participants reported exercising at the 6- and 12-month follow-up. However, very
      few individuals continued to practice TC on a regular basis (more than once a
      week) beyond the 12-week intervention. Balance confidence or incidence of falls
      did not improve.

PMID- 18821439
TI  - The role of the cerebellum in procedural learning--are there implications for
      physiotherapists' clinical practice?
AB  - Motor learning is the means by which we acquire skilled movements and consign
      them to permanent memory. Multiple brain areas are involved, and patients with
      neurological damage often experience difficulty when attempting to relearn
      previously learned skills. For these patients, the location of the lesion may be
      critical in influencing their motor skill relearning. The cerebellum has been
      described as an "on-line" comparator and corrector of movement, but recent
      research suggests that the cerebellum may also have a role in the later stages of
      motor learning, including the automation of movement patterns, although
      conflicting research in this area means that there is as yet no consensus. This
      knowledge may have implications for the way physiotherapists treat patients with
      cerebellar lesions. Some treatments in regular use by physiotherapists are
      discussed, and possible implications for practice are considered.

PMID- 18821440
TI  - Delisting publicly funded community-based physical therapy services in Ontario,
      Canada: a 12-month follow-up study of the perceptions of clients and providers.
AB  - Publicly funded community-based physical therapy (PT) services in Canada's most
      populous province of Ontario were partially delisted, or deinsured, in April
      2005. Two previous studies examined the short-term effects from the client and
      provider perspectives; and in this study, we follow up with participants from
      these preceding studies to assess long-term consequences of this policy. Sixteen
      of 18 providers (89%) and 64 of 98 clients (65%) agreed to participate in a
      follow-up telephone interview. Our results indicate that 12 months following
      delisting, and despite government assurances that access would be preserved,
      clients rendered ineligible for publicly funded services report ongoing access
      barriers across Ontario. Clients in this study also express concern about their
      overall health and report an increased use of other insured health professionals
      (e.g., physicians) and services (e.g., hospitals). On the other hand, providers
      within the network of publicly funded clinics report an important decrease in
      demand for PT services, whereas those from other settings report little change.
      We conclude that delisting policies may have long-term consequences on uninsured
      or underinsured clients and that evidence-based policy planning is warranted to
      ensure that the goals of reform are aligned with the desired outcomes at the
      client, provider, and system levels.

PMID- 18821441
TI  - Educational and professional issues in physical therapy--an international study.
AB  - Very little information exists regarding physical therapy educational and
      professional issues in various regions of the world. A better understanding may
      facilitate physical therapy (PT) practice, education, and research around the
      globe. The purpose of this study was to gain a worldwide perspective of physical
      therapy educational and professional issues in 40 separate countries. Forty
      countries known to provide PT were chosen from a World Confederation for Physical
      Therapy (WCPT) list of affiliates based on language, geography, and presumed PT
      practice. An English survey consisting of 22 items and four primary areas
      (accreditation of PT educational programs, licensure, specialization, and earning
      potential) was translated into five different languages (Spanish, French,
      Portuguese, Japanese, and Korean). The survey was administered electronically to
      key WCPT contacts in the 40 countries. The response rate was 42.5% and revealed
      modest diversity in physical therapy educational and professional issues among
      countries with the exception that 1) all but one country had an accreditation
      process for PT educational programs; 2) all but one country had licensure for
      PTs; and 3) all but five countries had a specialization process that included a
      written examination. Modest diversity in physical therapy educational and
      professional issues appears to exist among countries except for accreditation,
      licensure, and specialization.

PMID- 18821442
TI  - Comparisons of electromyographic activity of scapular muscles between elevation
      and lowering of the arms.
AB  - The aim of this study was to compare the electromyographic (EMG) activity levels
      of the serratus anterior, upper, middle, and lower trapezius muscles between
      elevation and lowering of the arms with 10 healthy subjects. The EMGs of each
      muscle was quantified and normalized for the complete movement, as well as for
      the six different phases of each movement. Repeated measure ANOVAs were used to
      investigate main and interaction effects between movements/sides and sides/phases
      (alpha<0.05). Significant differences were found between the elevation and the
      lowering of the arms for all muscles (p<or=0.001). However, there were no
      significant differences between sides (0.24<p<0.97), nor interactions between
      movements and sides (0.28<p<0.81) and between sides and phases (0.22<p<0.94) for
      all muscles. In addition, significant differences were found between phases for
      all muscles during elevation (p<or=0.001) and lowering of the arms
      (0.001<p<0.01). Despite the different patterns of activity of all muscles, there
      were some similarities: For both movements, dominance of the upper extremities
      did not appear to be an important variable to be considered; the serratus
      anterior was the only muscle that showed significant differences in EMGs between
      all phases; and the middle trapezius was the muscle that showed the longest
      plateau phase.

PMID- 18821443
TI  - Interrater reliability of the Modified Modified Ashworth Scale (MMAS) for
      patients with wrist flexor muscle spasticity.
AB  - The measurement of spasticity is part of the neurological examination of patients
      with disorders of the central nervous system. Recently, the Modified Modified
      Ashworth Scale (MMAS) was developed for the characterization of muscle
      spasticity. The purpose of this study was to determine the interrater reliability
      of the MMAS in the assessment of wrist flexor muscle spasticity in adult patients
      after upper motoneuron lesions resulted in hemiplegia. Thirty hemiplegic patients
      (17 males and 13 females) with a mean age of 55.6+/-7.8 years participated in
      this study. The wrist flexor spasticity was assessed according to MMAS by two
      female physiotherapists. The raters gave 23 patients the same spasticity score
      (weighted percentage agreement=97.4%). The most agreement occurred for scores 3
      (46.7%) and 0 (16.7%), respectively. The agreement between raters was very good
      (weighted kappa=0.92, SE=0.03, p<0.0001). In conclusion, the MMAS has very good
      interrater reliability for the assessment of wrist flexor muscle spasticity.

PMID- 18821444
TI  - Test-retest reliability of cervicocephalic relocation test to neutral head
      position.
AB  - Considering the important role of the cervical joint position sense on control of
      human posture and locomotion, accurate and reliable evaluation of neck
      proprioceptive abilities appears of great importance. Although the
      cervicocephalic relocation test (CRT) to the neutral head position (NHP) usually
      is used for both research and clinical purposes, its test-retest reliability has
      not been clearly established yet. The purpose of the present experiment was to 1)
      evaluate the test-retest reliability of the CRT to NHP and 2) to determine the
      number of trial recordings required to ensure reliable measurements. To this aim,
      40 young healthy adults performed the CRT to NHP on two separate occasions. Ten
      trials were performed for each rotation side. Absolute and variable errors,
      processed along their horizontal, vertical, and global components, were used to
      assess the cervical joint repositioning accuracy and consistency, respectively.
      Mean difference between test and retest with 95% confidence interval, intraclass
      correlation coefficient, and Bland and Altman graphs with limits of agreement
      were used as statistical methods for assessing test-retest reliability. Results
      show that the CRT to NHP when executed in its original form (i.e., 10 trials) has
      a fair to excellent reliability (ICC ranged from 0.52 to 0.81 and from 0.49 to
      0.77, for absolute and variable errors, respectively); the test-retest
      reliability of this test increases as the number of trials used to establish
      subject's repositioning errors increases; and using the mean of eight trials is
      sufficient to ensure fair to excellent reliability of the measurements (ICC
      ranged from 0.39 to 0.78 and from 0.44 to 0.78, for absolute and variable errors,
      respectively).

PMID- 18821445
TI  - Serological and genetic evidence for the presence of Seoul hantavirus in Rattus
      norvegicus in Flanders, Belgium.
AB  - Seoul hantavirus (SEOV), carried by Rattus rattus (black rat) and R. norvegicus
      (Norway, brown rat), was reported to circulate as well as cause HFRS cases in
      Asia. As Rattus sp. are present worldwide, SEOV has the potential to cause human
      disease worldwide. In Europe however, only SEOV prevalence in rats from France
      was reported and no confirmed cases of SEOV infection were published. We here
      report genetic and serological evidence for the presence of SEOV virus in brown
      rat populations in Belgium. We also serologically screened an at-risk group that
      was in contact with R. norvegicus on a daily basis and found no evidence for SEOV
      infection.

PMID- 18821446
TI  - Doing everyday life--experiences of the oldest old.
AB  - The purpose of this article is to explore how a group of elderly people, living
      and managing on their own, describe and experience their everyday doings.
      Interviews and observations were conducted with 18 community-living people aged
      85 and above. The experiences of 'Doing everyday life' are described in five
      overarching themes: 'Experiencing being old', 'Doings in everyday life',
      'Patterns of the day', 'Altered doings', and 'The importance of time'. What is
      done during an ordinary day does not differ much from earlier in life, but how
      the doings are performed has changed. Being occupied and staying healthy and
      sound in mind was stressed as important in old age and even if reduced energy and
      functional constraints limited the doings, a strong volition to manage
      independently was expressed. The participants perceived society as regarding the
      elderly as useless and worthless. Knowledge emanating from the very old
      themselves is vital to diversify the image of elderly people and to offer
      interventions and support adapted to their needs and desires.

PMID- 18821447
TI  - Longitudinal changes in everyday life after home modifications for people aging
      with disabilities.
AB  - OBJECTIVE: To investigate longitudinal impacts of home modifications on the
      difficulty of performing everyday life tasks for people aging with disabilities,
      and to investigate whether other factors had any additional impacts on difficulty
      in everyday life tasks for people receiving home modifications. METHODS: The
      sample consisted of 103 persons aging with disabilities and in need of home
      modifications, divided into an intervention group and a comparison group. The
      data were first subjected to Rasch analysis and a random coefficient model was
      used. RESULTS: Participants in the intervention group reported a significantly
      lower level of difficulty in everyday life tasks compared with those in the
      comparison group. One confounding factor, number of months waiting for home
      modification, had an impact on difficulty in everyday life. CONCLUSION: Home
      modifications are effective in decreasing difficulty in performing everyday life
      tasks up to six months after the installation. Furthermore, to be effective home
      modifications need to be installed in a timely fashion. For each consecutive
      month the person waited for their home modification the difficulty of performing
      everyday life tasks increased. Therefore, it is important that home modifications
      be installed as soon as possible after the need has been identified.

PMID- 18821448
TI  - Hand injury from powered wood splitters.
AB  - We describe the types of hand injury sustained from powered wood splitters.
      Information about all patients with such injuries treated at the Department of
      Hand Surgery, University Hospital, Uppsala, during the period 1995-2001 was
      collected from their records, and from written questionnaires and telephone
      interviews. Fourteen of the 131 patients found were below the age of 15. There
      was no change in the annual injury rate for inpatients. Wedge splitters caused
      82% and screw splitters 18% of all injuries. The part of the hand most often
      injured by screw splitters was the metacarpus and by wedge splitters the index
      finger. Screw splitters caused palmar perforation, avulsion of the thumb, and
      shredding injuries. Traumatic amputation and devascularising injuries were also
      common. Hand injury from powered wood splitters is an important and continuing
      problem. Most injuries are caused by wedge splitters, injuries caused by screw
      splitters differ from those caused by wedge splitters. Preventive measures are
      needed and should include keeping children away from splitters. Further research
      to facilitate prevention is warranted.

PMID- 18821449
TI  - Results of treatment of malignant soft tissue tumours in the groin.
AB  - Soft tissue sarcomas of the inguinal region are a challenge with regard to
      achieving clear margins, reconstruction of the femoral vessels, and soft tissue
      coverage. Six men aged 39 to 48 years and one woman of 56 were treated for soft
      tissue sarcomas of the groin. All patients were treated with local en bloc
      resections including the femoral artery, vein, and nerve. In two patients the
      soft tissue defect was covered primarily with an ipsilateral rectus abdominis
      muscle flap, in two others (because of wound dehiscence) coverage was achieved
      with the opposite rectus abdominis muscle pedicle flap as we were afraid of
      closure of the ipsilateral deep epigastric vessels. In the others local measures
      were sufficient, however, wound healing was usually delayed. Histopathological
      examination showed tumour-free margins in each case. One patient developed a
      local recurrence, but had had no radiotherapy because of problems with wound
      healing. A high rate of local tumour control in soft tissue sarcomas of the
      inguinal region can be achieved with the combination of surgical resection and
      radiotherapy. No compromise should be made with aggressive soft tissue coverage
      to protect the vascular reconstruction, control wound healing after neoadjuvant
      radiotherapy, or allow immediate adjuvant radiotherapy. At primary wound closure
      we would generally use an ipsilaterally distally pedicled rectus abdominis muscle
      flap if the deep epigastric vessels can be preserved or - if the ipsilateral
      vessels need be resected to achieve clearance of tumour - use a contralateral
      flap.

PMID- 18821450
TI  - Employment among users of a medically supervised safer injection facility.
AB  - A supervised injection facility (SIF), where individuals can inject drugs under
      medical supervision, opened in Vancouver in 2003. The scientific evaluation of
      the SIF has demonstrated positive public health-related outcomes. However, the
      influence of supervised injection facilities on individual efforts to reintegrate
      into mainstream society has not been studied. We examined for a possible
      relationship between use of the SIF and employment among a cohort of 1090 SIF
      users using generalized estimating equations (GEE). In a multivariate analysis of
      factors associated with employment, using the SIF for >or= 25% of injections
      (versus > 25% of injections) was not statistically significant (AOR = 1.05, 95%
      CI: 0.88-1.27). These findings suggest that the SIF is not having an adverse
      impact on efforts to seek employment.

PMID- 18821451
TI  - Oxcarbazepine in rapid benzodiazepine detoxification.
AB  - OBJECTIVE: This study aims at evaluating the tolerability and efficacy of the
      antiepileptic drug oxcarbazepine in benzodiazepine detoxification in ten
      patients. METHODS: In this case study of an inpatient withdrawal program, each of
      the ten patients was detoxified using oxcarbazepine and completed withdrawal
      successfully without the occurrence of withdrawal symptoms. The detoxification
      program followed an outlined dosage scheme with oxcarbazepine increase and
      benzodiazepine tapering. RESULTS: The rapidity of benzodiazepine detoxification
      using oxcarbazepine was remarkable, benzodiazepine withdrawal being completed in
      as little as 11 days. CONCLUSIONS: The results support the assumption that
      oxcarbazepine is a valuable drug for inpatient benzodiazepine withdrawal
      programs.

PMID- 18821452
TI  - High psychiatric symptom severity is a moderator of substance abuse treatment
      outcomes among women in single vs. mixed gender group treatment.
AB  - OBJECTIVE: This exploratory study examined psychiatric symptom severity as a
      moderator of outcomes among women receiving either the Women's Recovery Group
      (WRG), a new manualized group treatment for substance use disorders combining
      single-gender group composition and women-focused content, or Group Drug
      Counseling (GDC), an empirically supported mixed-gender group treatment. METHODS:
      We used a mixed model analysis of variance. RESULTS: We found a significant 3-way
      interaction effect of treatment condition, time, and baseline Brief Symptom
      Inventory scores as well as Beck Depression Inventory scores. CONCLUSION: Single
      gender group treatment may confer added benefit for women with substance abuse
      and high psychiatric symptom severity than mixed-gender treatment.

PMID- 18821453
TI  - Measuring recovery capital and determining its relationship to outcome in an
      alcohol dependent sample.
AB  - OBJECTIVE: The current study was conducted to determine whether items culled from
      multiple measures and identified by a consensus panel as indicators of recovery
      capital would cohere as a unified, meaningful measure predictive of outcome.
      METHODS: Three-hundred twenty-three alcohol dependent individuals receiving
      inpatient care completed multiple psychosocial instruments at treatment intake
      and three-month post-admission follow-up. RESULTS: Exploratory factor analysis
      supported the multi-dimensional nature of the recovery capital construct. Modest
      relationships with proximal and distal outcomes were observed. CONCLUSIONS:
      Further work aimed at designing a psychometrically sound measure that
      specifically assesses the assets that someone brings with them into substance
      abuse treatment is needed.

PMID- 18821454
TI  - Clinical pharmacokinetics of lofexidine, the alpha 2-adrenergic receptor agonist,
      in opiate addicts plasma using a highly sensitive liquid chromatography tandem
      mass spectrometric analysis.
AB  - OBJECTIVES: The objective of this investigation was to characterize the
      pharmacokinetic profile of lofexidine. Lofexidine is an orally bioavailable alpha
      2-adrenergic receptor agonist analogue of clonidine that acts centrally to
      suppress opiate withdrawal symptoms. METHODS: During the detoxification period of
      a phase 3 placebo-controlled, randomized, double-blind trial, six subjects were
      entered in this preliminary pharmacokinetic study. RESULTS: Pharmacokinetic
      analysis of plasma samples collected during study day 7 indicated that C(max) was
      3242 +/- 917 ng/L. The mean trough levels between the study days were not
      significantly different (p > .05), suggesting that the subjects were at steady
      state. CONCLUSIONS: Although preliminary due to the limited number of subjects,
      these findings are the first to document lofexidine clinical pharmacokinetics in
      opiate addicts using a highly sensitive liquid chromatography tandem mass
      spectrometric analysis.

PMID- 18821455
TI  - History of physical or sexual abuse and participation in 12-step self-help
      groups.
AB  - OBJECTIVES: Although 12-step groups are an important resource for managing
      substance use problems, their efficacy for patients with a physical or sexual
      abuse history is unknown. METHODS: In the present study, patients with a history
      of physical or sexual (n = 122) or no (n = 143) abuse were interviewed at entry
      to outpatient substance use treatment at the Veterans Administration. RESULTS:
      After adjusting for baseline substance use, physical or sexual abuse was
      associated with more attendance at and involvement in 12-step groups.
      Participation in 12-step groups predicted abstinence at one year, regardless of
      abuse history. CONCLUSIONS: Limitations and implications are discussed.

PMID- 18821456
TI  - The urban poor's economic profile of tobacco use.
AB  - OBJECTIVES: Low-income minority tobacco users are price sensitive and are more
      likely to quit when tobacco prices go up. No prior research documents economic
      characteristics of low-income tobacco users. The study investigates economic
      profile of tobacco use among urban low-income African Americans. METHODS: In this
      baseline study (n = 338), tobacco users and nonusers were compared, and their
      economic conditions of tobacco use including (current and past) employment
      barriers were examined. RESULTS: The study results demonstrate that tobacco use
      status appeared to be associated with employment barriers among low income
      populations. Controlling for other independent variables in the multivariate
      logistic regression model, previous criminal activity, planning to move out, and
      female gender were found to be linked to labor force status. CONCLUSIONS: More
      research efforts on how indigent tobacco-using individuals develop their
      employment skills and become economically independent are needed.

PMID- 18821457
TI  - Personality factors associated with methadone maintenance dose.
AB  - OBJECTIVES: Methadone is the most frequently prescribed medication for the
      treatment of opioid dependence in the U.S., and questions relating to appropriate
      dosing of methadone remain an important issue. Given accumulating evidence
      suggesting an elevated prevalence of personality pathology in opioid dependent
      populations, as well as evidence of an association between Cluster B
      characteristics and substance use severity, we hypothesized that patients with
      such pathology would have elevated methadone dose prescriptions. METHODS:
      Participants were 54 opioid dependent individuals recruited from a methadone
      maintenance clinic. RESULTS: RESULTS indicated that participants with symptoms
      consistent with Cluster B pathology had a significantly higher mean prescribed
      methadone dose relative to participants without Cluster B pathology. CONCLUSION:
      The presence of personality traits appears to influence methadone maintenance.
      Implications of this finding are discussed.

PMID- 18821458
TI  - Developing therapies for depression in drug dependence: results of a stage 1
      therapy study.
AB  - OBJECTIVE: This Stage 1b controlled trial sought a preliminary test of the
      relative efficacy of Behavioral Therapy for Depression in Drug Dependence (BTDD)
      against a structured relaxation intervention (REL) for treating DSM-IV depressive
      disorders and substance abuse. METHOD: Thirty-eight methadone maintained opiate
      dependent participants, who met criteria for a DSM-IV depressive disorder, were
      randomized to one of two, 24-week treatment conditions (BTDD or REL). RESULTS:
      Depression response, defined as at least a 50% reduction in Hamilton Depression
      Scale score from baseline to the end of study, was high and similar in both BTDD
      (61%) and REL (65%). Rates of drug use were low overall, both at baseline and at
      the end of study, and did not differ between treatment groups at study endpoint.
      CONCLUSIONS: The findings suggest that both behavioral- and relaxation-based
      approaches show promise for treating comorbid depression in drug dependent
      populations. Future work should examine combining or modifying these
      interventions to target substance use more directly and include values based
      methods for increasing more adaptive behavioral patterns.

PMID- 18821459
TI  - Screening current and future diagnosis of psychiatric disorders using the Revised
      Drug Use Screening Inventory.
AB  - The revised Drug Use Screening Inventory (DUSI-R) is a valid and reliable self
      report questionnaire used for quantifying problems that frequently precede and co
      occur with substance abuse. The present investigation determined whether the DUSI
      R's items can be aggregated into scales that implicate current and future
      psychiatric disorders. Scales were derived to screen for attention deficit,
      conduct, antisocial, anxiety, depression, and substance use disorders in a
      longitudinally tracked cohort of 328 boys. Evaluations were conducted when the
      boys were 12-14, 16, 19, and 22 years of age. All of the scales identified youths
      qualifying for current DSM-IV diagnosis with excellent accuracy. Predictive
      validity of the scales ranged from good to excellent. Accordingly cut-off scores
      were determined for each scale for use in practical settings to identify youths
      who require comprehensive diagnostic evaluation. Thus in addition to its utility
      for detecting problems that precede and correlate with substance abuse, the DUSI
      R is cost-efficient for screening youths for mental disorders.

PMID- 18821460
TI  - Overstating the cost savings from contraceptive use.

PMID- 18821461
TI  - Contraceptive applications of progesterone receptor modulators.
AB  - Currently developed progesterone receptor modulators (PRMs) are steroid-derived
      compounds with mild or potent antiprogestin activity. PRMs may exert a
      contraceptive activity by different mechanisms such as blockade of ovulation and
      endometrial desynchronization. Their potential clinical applications are manifold
      and are very promising in major public health areas, including emergency
      contraception, long term oestrogen-free contraception (administered alone, or in
      association with a progestin-only pill to improve bleeding patterns),
      endometriosis and myoma treatment. The mechanisms of their anti-ovulatory effects
      and of the endometrial modifications elicited during long term PRM treatment are
      still not fully elucidated. In future clinical applications, PRMs will be
      administered orally, via intrauterine systems or vaginal rings.

PMID- 18821462
TI  - Experience of IUD/IUS insertions and clinical performance in nulliparous women--a
      pilot study.
AB  - OBJECTIVES: To assess experience of insertion and use, by nulliparous women, of
      intrauterine devices (IUDs) and intrauterine systems (IUSs) and the feasibility
      of a large comparative study. METHODS: Prospective pilot study of women attending
      for interval insertion of IUD/IUS or emergency IUD. Problems and experience of
      the procedure were noted. At three months and one year continuation rates,
      satisfaction levels and problems were recorded. Case notes were reviewed for non
      responders. RESULTS: Between May and October 2005, 117 nulliparous women were
      recruited. Nine had an IUS inserted, and 104 an IUD. Despite a reasonable level
      of pain at insertion most women gave broadly positive descriptions of the
      procedure. At one year, 65 women were known to still have their original device.
      Fifteen had it removed; in six women it was expelled. The satisfaction score was
      high. There were no pregnancies or perforations. CONCLUSIONS: Insertion of
      IUD/IUS was well tolerated by the majority. Continuation and satisfaction rates
      were high. The IUD/IUS should be offered to nulliparous women as part of the full
      contraceptive menu. The ease of recruitment in this pilot study suggests that a
      larger study is feasible.

PMID- 18821463
TI  - The influence of peers on risky sexual behaviour during adolescence.
AB  - OBJECTIVES: To determine to what degree the predominance of risky sexual
      behaviour during adolescence is the result of social influence, in particular
      that of peers, according to the perception of their attitudes and sexual
      behaviour. METHODS: Data were collected through structured and confidential
      individual interviews with 100 adolescents, selected randomly from among 1467
      students attending one French high school. RESULTS: Although this study is of an
      exploratory nature, it reveals that the perception of peers is associated with a
      higher frequency of sexual initiation and commitment, including oral sex, but
      also commitment to protected sex. Sexual permissiveness of peers is associated
      with a higher frequency of sexual practices considered risky. The attitudes of
      peers with regard to contraception are associated with protective contraceptive
      attitudes, without a direct influence on behavioural patterns. CONCLUSIONS: The
      sexual norms of peers influence youths' individual attitudes and behaviours.
      Gender differences in sexual socialization also play a role. Both aspects must be
      taken into account when devising prevention programmes concerning adolescent
      sexuality.

PMID- 18821464
TI  - Religious beliefs prevailing among Somali men living in Finland regarding the use
      of the condom by men and that of other forms of contraception by women.
AB  - The objective of this study was to explore religious beliefs of Somali men
      residing in Finland that may influence their use of condoms and their perceptions
      of contraceptive use by women of their community. Both quantitative and
      qualitative methods were used to study 98 refugee Somali married men aged 30-65
      years. Participants filled in self-administered questionnaires (in English or in
      Somali) but were also interviewed. The interviews were semi-structured, featuring
      thematically clustered open-ended questions; they were conducted in Somali or in
      English. Participants had arrived in Finland between 1990-1998. They had from 2
      12 children. For religious reasons, 63% of the men avoided using condoms and were
      opposed to women's contraceptive use. The remaining 37% were not deterred by
      religious beliefs from using condoms and from approving women's contraceptive
      practices. In conclusion, for religious reasons, most Somali men assessed avoided
      using condoms and disapproved of the use of contraception by women.

PMID- 18821465
TI  - Cervical pregnancy: a case series and a review of current clinical practice.
AB  - Five consecutive cases of cervical pregnancy (CP) are presented. In four cases,
      the diagnosis was made at routine check-ups and these were all treated
      conservatively. In the fifth case, an erroneous diagnosis of inevitable abortion
      was made, in a patient presenting with profuse vaginal bleeding. Persistent
      bleeding following curettage required an emergency hysterectomy, after failure of
      compressive methods. From the four cases treated conservatively, three received
      standard methotrexate i.m. (MTX) in combination with bilateral uterine artery
      embolization (UAE). In one case MTX was followed by intraamniotic puncture and
      instillation of KCl due to persistent embryonic heartbeat. A spontaneous
      evacuation of the cervical pregnancy occurred in all patients treated
      conservatively. We postulate that the preventive use of uterine artery
      embolization in combination with standard MTX treatment could contribute to
      reduce the risk of excessive bleeding and facilitate spontaneous expulsion.
      Possible detrimental effects of the treatment on subsequent reproductive
      capacities and obstetrical outcome are also pointed out. The diagnostic methods
      and therapeutic approaches are discussed and the literature is reviewed. With
      referral to the first case of our series, which required an emergency
      hysterectomy, we want to stress the importance of an early diagnosis for a
      correct management of this condition.

PMID- 18821466
TI  - Pyosalpinx caused by the tubal migration of an intrauterine device--a case
      report.
AB  - Migration of an intrauterine device (IUD) is a complication occurring at or
      following insertion. After having perforated the uterine wall, the IUD usually
      will settle into the peritoneal cavity. Tubal migration of an IUD is extremely
      rare and little is known about its mechanism. We describe a case of pyosalpinx
      caused by the tubal migration of a copper IUD. The tail of the device was
      embedded in the mesocolon.

PMID- 18821467
TI  - One genotype, many phenotypes.

PMID- 18821468
TI  - Novel therapeutic agents targeting the glucocorticoid receptor for inflammation
      and cancer.
AB  - Glucocorticoids, through their interaction with the ubiquitous glucocorticoid
      receptor (GR), have extensive and disparate effects on different cells and
      tissues. They have long been used in the treatment of asthma, arthritis and
      autoimmune diseases based on their anti-inflammatory and immunosuppressive
      effects. For these reasons, as well as for their ability to induce massive
      apoptosis in hematological malignancies, they are also commonly used as
      cotreatment in cancers. Despite their wide usage, chronic glucocorticoid therapy
      has deleterious side effects, including weight gain, osteoporosis and diabetes
      mellitus, and has been shown to diminish the tumor toxicity of chemotherapy,
      preventing the full potential of glucocorticoid treatment from being realized.
      Technological advances have contributed to a better understanding of the
      mechanism of glucocorticoid action, prompting the development of tailored
      therapeutics targeting the desired outcomes of GR signaling. This review
      discusses recent advances in the development of novel therapeutic agents for
      inflammation and cancer through targeting the GR.

PMID- 18821469
TI  - Free fatty acid receptor family: novel targets for the treatment of diabetes and
      dyslipidemia.
AB  - Free fatty acids (FFAs) fuel physiological processes in various tissues, such as
      skeletal muscle, the heart, liver and pancreas. Malfunction of FFA-mediated
      signaling pathways, as well as FFA metabolism, has been correlated to pathologies
      such as type 2 diabetes and dyslipidemia. The recent deorphanization of the FFA
      receptor family has drawn attention to these G-protein-coupled receptors as
      potential therapeutic targets for the treatment of metabolic diseases.

PMID- 18821470
TI  - The endoplasmic reticulum as a potential therapeutic target in nonalcoholic fatty
      liver disease.
AB  - The endoplasmic reticulum (ER) has emerged as a key to understanding the
      development and consequences of hepatic fat accumulation in nonalcoholic fatty
      liver disease (NAFLD). An essential function of this organelle is the proper
      assembly of proteins that are destined for intracellular organelles and the cell
      surface. Recent evidence suggests that chemical chaperones that enhance the
      functional capacity of the ER improve liver function in obesity and NAFLD. These
      chaperones may therefore provide a novel potential therapeutic strategy in NAFLD.

PMID- 18821471
TI  - Advances in immunotherapy of castration-resistant prostate cancer:
      bisphosphonates, phosphoantigens and more.
AB  - Medical progress has prolonged life expectancy in patients with castration
      resistant prostate cancer; however, the lack of effective therapies has fuelled
      an intensive search for novel modalities, including immunotherapy. Human
      gammadelta T-cells can be activated by endogenous pyrophosphates
      (phosphoantigens), or by agents that provoke their accumulation. Among the
      latter, aminobisphosphonates are well-established in the clinic. In this review,
      the possibility that the intentional activation of gammadelta T-cells in vivo by
      phosphoantigens, or aminobisphosphonates and interleukin-2, may represent a
      promising target for the design of novel and highly innovative immunotherapy in
      patients with prostate cancer is discussed.

PMID- 18821472
TI  - The anti-aging, metabolism potential of SIRT1.
AB  - SIRT1 (sirtuin 1) is the human ortholog of the yeast Sir2 (silent information
      regulator 2) protein, which is implicated in lifespan extension in model
      organisms, such as yeast, worms and flies. It is an NAD+-dependent protein
      deacetylase with over two dozen known substrates that affect a wide variety of
      cellular processes, ranging from metabolism, cell cycle, growth and
      differentiation, inflammation, senescence, apoptosis, stress response and aging.
      Even though SIRT1 has been linked to calorie restriction-mediated longevity in
      model organisms, the mechanism by which it extends lifespan in mammals is not
      fully understood. A growing body of evidence suggests a role of SIRT1 in
      maintaining energy and nutrient homeostasis, thereby linking its anti-aging
      property to its role in metabolism.

PMID- 18821473
TI  - Application of ghrelin to gastrointestinal diseases.
AB  - This review outlines recent findings related to the therapeutic potential of
      ghrelin agonists or antagonists for the treatment of gastrointestinal (GI)
      motility disorders and the regulation of the hypothalamic control of feeding. The
      ability of ghrelin to promote GI motility in patients with postoperative ileus or
      gastroparesis, and to restore the normal feeding pattern and energy balance in
      the elderly and in cancer patients with impaired appetite are highlighted. A
      critical analysis of the possible mechanism of action and the potential benefits
      of using synthetic ghrelin agonists is based on data from preclinical research
      and recent clinical studies.

PMID- 18821474
TI  - Dexlansoprazole, a modified release formulation of an enantiomer of lansoprazole,
      for the treatment of reflux esophagitis.
AB  - Takeda Pharmaceutical Co Ltd is developing dexlansoprazole, an oral controlled
      release formulation of an enantiomer of lansoprazole, for the treatment of reflux
      esophagitis. By January 2008, an NDA for gastric acid-related diseases had been
      filed with the FDA, and the drug was undergoing phase II trials in Japan for
      gastroesophageal reflux disease.

PMID- 18821475
TI  - Taranabant, a novel cannabinoid type 1 receptor inverse agonist.
AB  - Merck & Co Inc is developing the cannabinoid receptor type 1 inverse agonist
      taranabant for the potential treatment of obesity and nicotine dependence. By
      October 2006, the drug had entered phase III trials for obesity, and by May 2008,
      a phase II study of taranabant as an aid to smoking cessation in chronic
      cigarette smokers had been completed.

PMID- 18821476
TI  - [Ultrafast MR sialography: comparison of two coil systems including an
      alternative surface coil].
AB  - PURPOSE: To compare the visualization of salivary ducts by ultrafast magnetic
      resonance sialography (MR sialography) using an alternative surface coil and a
      conventional head-neck coil. MATERIALS AND METHODS: In 11 healthy volunteers,
      ultrafast MR sialography (single shot turbo spin echo; acquisition time, 2.8 s)
      was performed before and after oral application of a sialogogue. Each subject
      received examinations with both a bilateral surface coil (SC) and a conventional
      head-neck coil (HNC). The depiction of parotideal and submandibular duct systems
      was graded from 1 to 5 (5 = poor) by four independent radiologists. ANOVA served
      for statistical analysis of duct rankings, and interobserver variability was
      determined by Intraclass Correlation Coefficient (ICC). RESULTS: With an
      excellent ICC of 0.96, both coil systems offered symmetric visualization of
      salivary ducts, and the image quality increased after oral application of
      sialogogue (p < 0.001). In total, the overall rating was worse for SC than for
      HNC (2.13 +/- 1.24 vs. 1.45 +/- 0.65, p < 0.001). SC was especially inferior in
      depiction of submandibular and extraglandular duct components compared to HNC (p
      < 0.001). CONCLUSION: Most notably due to the reduced visualization of
      extraglandular and submandibular ducts, the specific surface coil used in this
      study was inferior in image quality and does not constitute a reasonable
      alternative to conventional coil systems.

PMID- 18821477
TI  - [Traces of the 2nd World War. The relationship between childhood experiences and
      mental health in advanced age].
AB  - Based on the results of the Mannheim Cohort Study, a possible causal relationship
      between childhood experiences and the long-term course of predominantly
      psychosocially influenced disorders was examined, focussing on global development
      terms and war experiences. A sample of 26 individuals born in 1935 was
      investigated over a period of approximately 25 years. Psychosomatic impairment
      was assessed using a standardized expert rating (BSS impairment score) with high
      reliability. We found strong evidence that global development terms make an
      impact on mental health in advanced age. The amount of war experiences was not
      correlated with psychosomatic impairment in later life. Furthermore, war
      determined fathers' absence during childhood was not a predictor of psychosomatic
      impairment in later life. Methodical problems and consequences of these findings
      are discussed.

PMID- 18821478
TI  - [The trauma of miscarriage--factors influencing the experience of anxiety after
      early pregnancy loss].
AB  - The experience of miscarriage results in tremendous emotional disturbance for
      many affected women. Depression, anxiety, (pathological) grief, and posttraumatic
      stress symptoms are commonly experienced reactions. Several factors influence the
      level of emotional distress, like age, previous experience of miscarriage, or
      social support. In this work, we investigated the level of emotional distress
      after miscarriage using a novel methodological approach. Through the world wide
      web, N = 500 texts of women who reported freely on their miscarriage were
      accessed and analyzed using the Dresden Anxiety Dictionary, a German computerized
      version of the Gottschalk-Gleser speech analysis. The women were 28 years old on
      average. The texts were written, on average, about 28 days after the miscarriage.
      Women's pregnancy had lasted between 2 and 40 weeks (M = 12). The scores
      pertaining to death anxiety and mutilation anxiety were higher than the norm.
      More than 20 % of the women reported an increased level of anxiety. Variables
      that influenced the level of anxiety were age, time since miscarriage, duration
      of pregnancy, previous miscarriage, and social support. The results underscore
      the need for treatment, at least for sub-groups of affected women who have a
      higher risk for a complicated course of coping with miscarriage.

PMID- 18821480
TI  - [Experience with serological diagnosis of chikungunya fever].
AB  - BACKGROUND: During the year 2006 first imported cases of chikungunya fever in
      Europe occured contextual to the epidemic in the area of Indian ocean. In summer
      2007 also autochthonnic chikungunya infections in the northern part of Italy
      appeared. On the basis of these facts serologic diagnostics of chikungunya fever
      was initiated in the National Reference Laboratory (NRL) for Arboviruses of the
      Czech Republic. MATERIAL AND METHODS: Complement-fixation assay was estabilished
      in 2006. Micromodification of virus-neutralisation assay in 96-well plate with
      staining of the cell cultures for detection of anti-chikungunya v. antibodies was
      developed and estabilished for improvement of the diagnostics in 2007.
      Consequently in 2008 the diagnostics was completed with indirect
      immunofluorescence assay for detection of anti-chikungunya v. IgG and IgM
      antibodies using the commercial EUROIMMUN assay. Principle of virus
      neutralisation and the test procedure is described in the paper. Results reached
      by the use of all these methods are compared. RESULTS: From February 2006 to
      February 2008 110 serum samples from 104 persons were tested for anti-chikungunya
      v. antibodies. In 4 pateints acute chikungunya v. infection was proved and two
      other persons revealed seropositivity without acute infection. CONCLUSIONS:
      Qualitative correspondence between the particular methods was demonstrated and a
      benefit of virus-neutralisation assay for confirmation of the results was proved.

PMID- 18821481
TI  - [Differential diagnosis of hemorrhagic fever].
AB  - Viral hemorrhagic fevers(VHFs) are taken by common population, often also by
      science society, as only exotic diseases, which can not occur in our country. But
      the risk of importation of one of these diseases is very real. In the first part,
      basic information about microbiology, epidemiology and clinical manifestation is
      presented. In the second part, other diseases with similar manifestation are
      described. The last part is focused on basic information about treatment and
      prophylaxis.

PMID- 18821482
TI  - [Listeriosis a review of current knowledge].
AB  - The study includes a recent review of the epidemiology, pathogenesis and clinical
      picture of listeriosis and new data concerning its treatment.

PMID- 18821483
TI  - [Listeriosis - four case reports].
AB  - The authors described four cases of listeria infection. The patients were
      hospitalized in the Department of Infectious Diseases of the Masaryk Hospital in
      Usti nad Labem during the epidemic outbreak of this infection around the turn of
      2006/2007. The disease in three of the four patients was manifested as purulent
      meningitis and in the remaining one as a sepsis. All of the patients were above
      the age of 55 years; moreover, two of them were assumed to be immunocompromised.
      In three of the patients, whose laboratory findings revealed purulent meningitis,
      direct microscopy of cerebrospinal fluid (CSF), specific latex agglutination test
      and PCR were negative. Final diagnosis was determined on the basis of the CSF and
      blood cultures reported 3-4 days after collection. None of the patients suffered
      from diarrhoea. In the epidemiological anamnesis, only two of them admitted
      consumption of food that could become source of infection. The patients were
      successfully treated with either ampicillin and chloramphenicol.

PMID- 18821484
TI  - [Multiple brain abscesses of odontogenic origin caused by Fusobacterium
      nucleatum].
AB  - Infection caused by the anaerobic gram-negative rod Fusobacterium nucleatum
      belongs to endogenous infections. A 41-year-old man developed multiple brain
      abscesses of odontogenic origin. The main causes were poor oral hygiene and no
      dental check-ups. Pus aspired from a site in the brain contained DNA of the
      bacterium Fusobacterium nucleatum. Several teeth with periapical abscesses were
      extracted. Initially, the patient was treated empirically with a combination of
      cefotaxime and metronidazole (18 days). Subsequently, co-trimoxazole and
      rifampicin were administered (8 months). Four and eight months after the onset of
      the disease, MRI scans revealed only persistent residual changes in the brain
      parenchyma; the patient was asymptomatic, with no neurological signs and back at
      work.

PMID- 18821485
TI  - Blinding in peer review.

PMID- 18821486
TI  - Four-year experience with methotrexate exposures.
AB  - INTRODUCTION: Unintentional methotrexate (MTX) acute oral overdose is rarely
      reported. METHODS: We conducted a retrospective chart review of all human
      exposure calls (>150,000 charts) for MTX ingestions reported to our Poison Center
      during 2000-2003. RESULTS: Thirteen patients met the criteria. The average amount
      of MTX ingested was 13.03 mg (data from 7 cases), and the average patient age was
      43 years (20 months to 80 years). No significant toxicities occurred. DISCUSSION:
      Although intravenous MTX toxicity can be severe, this does not appear to be a
      phenomenon associated with either acute unintentional or suicidal oral ingestion.

PMID- 18821487
TI  - Poisoning hospitalization correlates with poison center call frequency.
AB  - INTRODUCTION: Poison Control Centers (PCCs) have been shown to reduce health
      expenditures by reducing emergency department and clinic visits. The effect or
      association of PCC call frequency on acute hospitalization rates for poisonings
      has not been studied extensively. METHODS: All nonfederal hospital discharges for
      acute poisoning principal diagnosis codes (960-979, 980-989, 9956X, 3030, and
      005) in California between October 1999 and June 2002 were examined.
      Approximately 3.3% of the discharges had county/hospital information suppressed
      in the public-use database because of confidentiality criteria and were excluded
      from the analysis. U.S. Census Bureau population estimates for appropriate years
      by counties were also obtained. The 58 California counties were condensed to 48
      counties and 3 "small-county" geographic groupings. Exposure calls by
      counties/groupings to the California Poison Control System(CPCS) for the same
      period were tabulated. RESULTS: In California, rates of hospital discharges for
      poisoning averaged 0.54/1000 person years with a range of 0.25/1000 person years
      (Central Counties) to 1.53/1000 person years (Del Norte County). Poison call
      rates averaged 8.5/1000 person years with a range of 4.9/1000 person years (Los
      Angeles County) to 19.6/1000 person years (Napa County). Poisoning discharges per
      1000 person years positively correlated with PCC calls per 1000 person years
      (Spearman correlation 0.41, p = 0.0003). The average hospital length of stay
      (LOS) did not correlate with PCC call frequency or poisoning discharges per 1000
      person years. CONCLUSION: The CPCS call frequency or county penetrance was not
      correlated with a reduction in the number of hospitalizations for poisoning nor
      was it associated with reduced average LOS in this study. Further study is needed
      to understand the etiology of the large differences in county rates of poisoning
      hospitalization and average LOS.

PMID- 18821488
TI  - Toxicity in rhesus monkeys following administration of the 8-aminoquinoline 8-[(4
      amino-l-methylbutyl)amino]- 5-(l-hexyloxy)-6-methoxy-4-methylquinoline
      (WR242511).
AB  - INTRODUCTION: Many substances that form methemoglobin (MHb) effectively counter
      cyanide (CN) toxicity. Although MHb formers are generally applied as treatments
      for CN poisoning, it has been proposed that a stable, long-acting MHb former
      could serve as a CN pretreatment. Using this rationale, the 8-aminoquinoline
      WR242511, a potent long-lasting MHb former in rodents and beagle dogs, was
      studied in the rhesus monkey for advanced development as a potential CN
      pretreatment. METHODS: In this study, WR242511 was administered intravenously
      (IV) in 2 female and 4 male rhesus monkeys in doses of 3.5 and/or 7.0 mg/kg; a
      single male also received WR242511 orally (PO) at 7.0 mg/kg. Health status and
      MHb levels were monitored following exposure. RESULTS: The selected doses of
      WR242511, which produced significant methemoglobinemia in beagle dogs in earlier
      studies conducted elsewhere, produced very little MHb (mean < 2.0%) in the rhesus
      monkey. Furthermore, transient hemoglobinuria was noted approximately 60 minutes
      postinjection of WR242511 (3.5 or 7.0 mg/kg), and 2 lethalities occurred (one IV
      and one PO) following the 7.0 mg/kg dose. Myoglobinuria was also observed
      following the 7.0 mg/kg dose. Histopathology analyses in the 2 animals that died
      revealed liver and kidney toxicity, with greater severity in the orally-treated
      animal. CONCLUSIONS: These data demonstrate direct and/or indirect drug-induced
      toxicity. It is concluded that WR242511 should not be pursued as a pretreatment
      for CN poisoning unless the anti-CN characteristics of this compound can be
      successfully dissociated from those producing undesirable toxicity.

PMID- 18821489
TI  - Cardiovascular toxicity associated with recreational use of diphenylprolinol
      (diphenyl-2-pyrrolidinemethanol [D2PM]).
AB  - INTRODUCTION: Many countries have specific legislation, such as the Controlled
      Substances Act (1970) in the United States and the Misuse of Drugs Act (1971) in
      the United Kingdom to control recreational drugs. There is a growing market and
      supply of "novel" recreational drugs that are not covered under appropriate
      legislation, despite having similar chemical structures and/or clinical effects.
      In addition, these novel drugs are often sold legally on the street or through
      the Internet, with limited details of the exact contents, making application of
      the appropriate legislation difficult. CASE REPORT: A male patient with no risk
      factors for ischemic heart disease, presented to our emergency department with
      agitation and chest pain characteristic of ischemia following the ingestion of
      two units of "Head Candy." He improved with oral diazepam over a period of 12
      hours and there was no biochemical evidence of myocardial damage. Serum analysis
      demonstrated the presence of diphenylprolinol (diphenyl-2-pyrrolidinemethanol
      [D2PM]) and glaucine at concentrations of 0.17 mg/L and 0.10 mg/L, respectively.
      No other recreational drugs were detected in an extensive toxicological screen of
      blood and urine samples. DISCUSSION: This is the first reported case of confirmed
      toxicity associated with recreational use of diphenylprolinol in combination with
      glaucine. In our view, this case provides further support for the need for a
      systematic approach to toxicological screening of patients with recreational drug
      toxicity to identify emerging drugs and provide evidence for legislative
      authorities to assist in revising the legal status of recreational drugs.

PMID- 18821490
TI  - Lithium overdose with electrocardiogram changes suggesting ischemia.
AB  - BACKGROUND: Lithium toxicity is associated with electrocardiogram (ECG) changes,
      but changes suggestive of an ST segment elevation myocardial infarction have not
      been reported. CASE REPORT: A 46-year-old incarcerated man suffering from
      diabetes, hypertension, and schizoaffective/bipolar disorder was treated with
      lithium 1,200 mg twice daily. Two days prior to presentation the patient became
      confused, ataxic, and anorexic in jail. Lithium level was 4.69 mmol/L. He was
      transferred to the emergency department. On arrival, vital signs were normal. The
      ECG showed a normal sinus rhythm. ST segments were elevated in the anterior leads
      with downward concavity. T waves were biphasic. Since these changes suggested
      cardiac ischemia and the patient was unable to respond to questions about chest
      pain, cardiac enzymes and an emergent echocardiogram were done. Troponin I was
      less than 0.1 microg/L. Echocardiogram was normal, without wall motion
      abnormalities. Treatment was with hemodialysis and whole-bowel irrigation.
      Postdialysis lithium level was 1.30 mmol/L. Over the next several days,
      electrocardiogram normalized. His speech gradually became coherent. After a 1
      week hospitalization, he returned to jail. CONCLUSION: Lithium intoxication can
      cause transient ST segment elevations suggesting an acute myocardial infarction.
      In the absence of a clear history, echocardiogram and cardiac enzymes can be used
      to rule out a myocardial infarction.

PMID- 18821491
TI  - Cardiotoxicity after massive amantadine overdose.
AB  - INTRODUCTION: Amantadine hydrochloride is an antiviral medication used as therapy
      for parkinsonism and as a cognitive enhancer. We report 2 cases of massive, acute
      ingestion of amantadine hydrochloride confirmed with serial serum levels. CASE
      REPORTS: A 47-year-old woman presented to the emergency department (ED) 30
      minutes after ingesting 10 g of amantadine (150 mg/kg) by her report. Initial ECG
      revealed a sinus rhythm with rate of 93 bpm, and a QRS of 84 msec. While in the
      ED, the patient sustained a pulseless cardiac arrest and the monitor revealed
      ventricular tachycardia. She was successfully defibrillated. Postdefibrillation
      ECG showed a sinus rhythm (rate = 82 bpm), QRS of 236 msec, and QTc of 567 msec.
      The serum potassium was 1.0 mEq/L (1.0 mmol/L). The patient was given 300 ml (300
      cc) 3% sodium chloride IV over 10 minutes. Ten minutes after completion of the
      hypertonic saline infusion, the patient's ECG abnormalities resolved and the QRS
      was 88 msec. Her potassium was repleted over the next 11 hours postpresentation,
      and she also received an IV bolus of 4 g of magnesium sulfate immediately after
      the cardiac arrest. No further hypotension, dysrhythmia, conduction delay, or
      ectopy was noted during the patient's hospital stay. The second case involved a
      33-year-old female patient who presented 1 hour after ingesting 100 tablets of
      amantadine hydrochloride (100 mg/tab). Initial ECG revealed sinus tachycardia
      with a QRS of 113 msec, an R wave in lead aVR of 4-5 mm and a QTc of 526 msec.
      Her serum potassium was 3.0 mEq/L (3.0 mmol/L), her serum calcium was 9.4 mg/dl
      (2.35 mmol/L), and serum magnesium was 2.1 mg/dl (0.86 mmol/L) on labs drawn at
      initial presentation. The patient was intubated for airway protection, and her
      potassium was repleted and corrected over the next 9 hours. Her ECG abnormalities
      improved 8 hours after initial presentation and normalized at approximately 14
      hours postingestion. The patient was discharged home 11 days after her ingestion.
      CONCLUSION: Acute amantadine toxicity manifests with life-threatening
      cardiotoxicity. Concurrent, often profound, hypokalemia may complicate the
      administration of sodium bicarbonate in the management of cardiac dysrhythmias.

PMID- 18821492
TI  - Fatality in a case of envenomation by Crotalus adamanteus initially successfully
      treated with polyvalent ovine antivenom followed by recurrence of
      defibrinogenation syndrome.
AB  - INTRODUCTION: Recurrences of clinical or laboratory manifestations of North
      American pit viper envenomation may happen despite control of the envenomation
      syndrome by prompt and adequate antivenom therapy. Recurrences of coagulopathy in
      victims of Eastern diamondback rattlesnake envenomation are generally regarded as
      benign. The vast majority suffer no actual bleeding despite florid coagulation
      laboratory abnormalities due to selective defibrinogenation. CASE REPORT: We
      report what we believe to be the first fatality following successful control of
      the envenomation syndrome following ovine antivenom treatment resulting from
      envenomation by a bite from the Eastern diamondback rattlesnake. This case raises
      the question of whether such recurrences are in fact benign, causal, or
      coincidental. This patient sustained significant brain hemorrhage and death
      ensued due to generalized cerebral edema. Defibrinogenation occurred 4 days after
      treatment with ovine antivenom. DISCUSSION: Coagulation abnormalities following
      Eastern diamondback rattlesnake envenomation are due to selective
      defibrinogenation. This is separate from disseminated intravascular coagulation
      (DIC). Thrombin generation, thus hemostasis, are generally considered normal.
      This case may cause reexamination of this belief.

PMID- 18821493
TI  - Intravenous lipid emulsion for local anesthetic toxicity: a review of the
      literature.
AB  - INTRODUCTION: The use of intravenous lipid emulsion (IVLE) has been proposed as a
      new potential treatment for local anesthetic toxicity. Local anesthetics work
      through reversible binding at sodium channels, and signs and symptoms of toxicity
      include central nervous system and cardiovascular effects. Cardiovascular
      collapse is a potential result of local anesthetic toxicity, and is generally
      resistant to resuscitation efforts with standard measures. DISCUSSION: Various
      animal studies have been published investigating the use of IVLE in local
      anesthetic toxicity. IVLE has been shown to increase the lethal dose of
      bupivacaine required, resuscitate animals that underwent local anesthetic-induced
      cardiovascular collapse, and more quickly reduce the amount of local anesthetic
      in the myocardium (compared to administration of control solution). Four human
      case reports utilizing IVLE for presumed local anesthetic toxicity, with varying
      presentations, are reviewed. CONCLUSIONS: IVLE has shown to be an interesting
      prospect for local anesthetic toxicity. Human case reports have shown successful
      resuscitation with use of IVLE, using varying dosing regimens. More studies are
      needed to determine the optimal dosing regimen, as well as to determine the
      potential adverse effects of IVLE when used in this setting.

PMID- 18821494
TI  - Case files of the University of Massachusetts fellowship in medical toxicology:
      lethal dose of opioids contained in an elastomeric capsule labeled as vancomycin.
AB  - A 67 year-old male presented to the emergency department with alteration in
      mental status. On arrival he had vital signs: pulse 110, BP 173/83, respiratory
      rate 4, oxygen saturation 57% and temperature 36.1 degrees Celsius. His past
      medical history included hypertension, vitamin B12 deficiency, hyperlipidemia,
      and recurrent cellulitis treated with vancomycin. The patient had no response to
      noxious stimuli, pinpoint pupils, and agonal respirations. Secondary to his
      wife's vehement denial that he had access to or history of using any narcotics,
      he was intubated after 2.2mg IV naloxone failed to reverse respiratory
      depression. Thirty minutes before presentation, however, he had received an
      intravenous infusion of vancomycin administered by his wife at home. The
      vancomycin, obtained from a home infusion medication supply company, was
      contained in one of five sealed elastomeric capsules delivered earlier that day.
      A qualitative comprehensive toxicology screen of urine for 1043 substances
      identified morphine, codeine, naloxone, lidocaine and caffeine. The original
      elastomeric container was not available for testing, but another container from
      the same delivery was submitted for testing to the state forensic laboratory.
      This intact container was labeled as Vancomycin 1g in 240mL of normal saline. The
      forensic laboratory confirmed that the alkaloidal contents of the elastomeric
      capsule were 10% codeine, 4.4% 6-monoacetyl morphine, and 84% morphine. No
      vancomycin was identified in the infusion bottles. The case was referred to the
      local police department and the state department of health drug control board.
      The home infusion company was also immediately notified to prevent similar
      occurrence. CONCLUSION: We are reporting the first known case of opioid overdose
      from an adulterated elastomeric capsule that was labeled as containing an
      antimicrobial agent.

PMID- 18821495
TI  - Update on research and activities at the Centers for Disease Control and
      Prevention, and the agency for toxic substances and disease registry.

PMID- 18821496
TI  - Selected abstracts from the 6th Asia Pacific Association of Medical Toxicology,
      Part 1.

PMID- 18821498
TI  - [Universal newborn hearing screening--a silent revolution].
AB  - Significant hearing loss is one of the most frequent congenital diseases and
      present at birth in approximately one in 1000 newborns. During the first years of
      life, this number of children with permanent hearing loss rises by approximately
      the same amount. Hearing impairment is not an obvious condition in newborns in
      most cases and produces very few signs in infancy. Such hearing loss threatens
      normal speech and personality development. The longer the child is without
      auditory stimulation by speech, the more difficult it is to acquire the missed
      linguistic skills. Therefore, early detection and rehabilitation of such hearing
      loss is crucial. Universal newborn hearing screening is the most effective method
      to detect such impairment and is based on objective audiometric test methods that
      were recently developed and adapted for screening requirements. Useful tests are
      otoacoustic emissions and the auditory brainstem response. This article reviews
      this new screening tests in general and with special regard to the situation in
      Switzerland.

PMID- 18821499
TI  - [Recurrent febrile episodes in childhood. From immunodeficiency to normality].
AB  - Fever is one of the leading symptom in childhood diseases. If there are recurrent
      febrile episodes, one have to distinguish between recurrent infections in the
      normal age range, periodic fever syndromes or even a primary immunodeficiency.
      Diagnostic tools to distinguish one from another are reported. The warning signs
      for primary immunodeficiency are listed and discussed. For periodic fever
      syndromes, the PFAPA syndrome, the most frequent in Swiss children, is discussed
      in some detail.

PMID- 18821500
TI  - [Bronchial asthma in childhood. A survey].

PMID- 18821501
TI  - [The role of thoracoscopy in paediatric spontaneous pneumothorax].
AB  - Spontaneous pneumothorax in children is an emergency. A rapid and structured
      treatment is necessary. Indicating clinical signs are dyspnoea with unilateral
      reduced breath sounds and hypersonic percussion note. Chest x-ray confirms
      diagnosis. CT scan shows detailed information's of pathological changes in lung
      tissue and offers important considerations for the therapy. Today video assisted
      thoracoscopic surgery (VATS) takes a central role in the treatment of spontaneous
      pneumothorax. Thoracoscopy completes diagnosis detecting the pathologies, which
      were missed in imaging procedures. Definitive surgical treatment is performed
      simultaneously in the same anaesthesia.

PMID- 18821502
TI  - [Varicella pneumonia].
AB  - The seroprevalence of chickenpox in countries with temperate climate is very high
      among young people. Only 4% of the infections occur in adults but the clinical
      course is usually more severe than in children. In adults, The mortality is
      approximately 40 times higher and the complication rate 25 times higher than in
      children. Pneumonia is the most frequent complication in adults and may be
      extremely severe in immunocompromised patients and in pregnant women. Pneumonia
      must be promptly treated with intravenous aciclovir. Vaccination is indicated in
      young seronegative patients with supplemental risk factors for severe
      complications. It is also effective post exposure, preventing or modifying the
      illness course in up to 90% of exposed people if given within 3 days.
      Immunoglobulins may be effective as late as 96 hours after exposure. They are
      frequently used for exposed people at high risk of severe disease, when varicella
      vaccine is contraindicated.

PMID- 18821508
TI  - [Bluetongue disease in Swiss sheep breeds: clinical signs after experimental
      infection with bluetongue virus serotype 8].
AB  - Clinical disease of bluetongue (BT) in sheep may differ depending on breed, age
      and immunity of infected sheep and may also vary between serotype and strain of
      BT virus (BTV). Since there are no data available on the susceptibility of Swiss
      sheep breeds for BT, we performed experimental infection of the 4 most common
      Swiss sheep breeds and the highly susceptible Poll Dorset sheep with the BTV
      serotype 8 (BTV-8) circulating in Northern Europe since 2006. Clinical signs were
      assessed regarding severity, localisation, progression and time point of their
      appearance. The results clearly show that the Swiss sheep breeds investigated
      were susceptible to BTV-8 infection. They developed moderate, BT-characteristic
      symptoms, which were similar to those observed in Poll Dorset sheep. Regardless
      of breed, the majority of infected animals showed fever, swelling of the head as
      well as erosions of the mouth and subcutaneous haemorrhages.

PMID- 18821509
TI  - [Effects of a two-year dairy herd health management programme on udder health,
      use of antibiotics and longevity].
AB  - Since 2003, the Research Institute of Organic Agriculture (FiBL) is realizing a
      herd health management programme ("pro-Q" project) focussing on udder health. The
      objectives of the project are: (1) to reduce antibiotic mastitis treatments, (2)
      to optimise udder health and (3) to improve longevity, measured as averaged
      number of herd lactations. The farms get expert advice in prevention and
      treatment on herd- and animal-level. After 2 years, treatment recordings of the
      65 investigated farms showed that antibiotic mastitis therapies were reduced from
      38 to 26 treatments per 100 cows and year (equals a reduction of 32%). Lactation
      numbers of the herds increased significantly by 0.2 lactations from 3.3 to 3.5
      lactations per cow. Udder health remained constant over all farms during 2 years:
      theoretical bulk milk cell counts averaged constantly at around 180000 cells/ml.
      Improvement of udder health on farm level was significantly influenced by higher
      somatic cell count when the project started and enhanced by farmer's motivation
      and farm-veterinarians' commitment to the project.

PMID- 18821510
TI  - Influence of pre-anaesthetic thoracic radiographs on ASA physical status
      classification and anaesthetic protocols in traumatized dogs and cats.
AB  - The purpose of this study was to evaluate if pre-anaesthetic thoracic radiographs
      contribute to the anaesthetic management of trauma patients by comparing American
      Society of Anesthesiologists Physical Status Classification (ASA grade) with and
      without information from thoracic radiography findings. Case records of 157 dogs
      and cats being anaesthetized with or without post-traumatic, pre-anaesthetic
      chest radiographs were retrospectively evaluated for clinical parameters,
      radiographic abnormalities and anaesthetic protocol. Animals were retrospectively
      assigned an ASA grade. ASA grades, clinical signs of respiratory abnormalities
      and anaesthesia protocols were compared between animals with and without chest
      radiographs. The group of animals without pre-anaesthetic radiographs was
      anaesthetized earlier after trauma and showed less respiratory abnormalities at
      presentation. The retrospectively evaluated ASA grade significantly increased
      with the information from thoracic radiography. Animals with a higher ASA grade
      were less frequently mechanically ventilated. Pre-anaesthetic radiographs may
      provide important information to assess the ASA grade in traumatized patients and
      may therefore influence the anesthesia protocol.

PMID- 18821511
TI  - Thymectomy in a cat with myasthenia gravis: a case report focusing on
      perianaesthetic management.
AB  - An 8 years old male persian cat with a diagnosis of myasthenia gravis was
      scheduled for transternal thoracotomy. An anterior mediastinal mass, suspected to
      be a thymoma, had to be resected. Progressive paraparesis and reduced ocular
      reflexes and menace response were the main clinical features. At the preoperative
      examination the cat appeared free of significant myocardial or respiratory
      diseases. The possibility of compromised respiratory function due to muscle
      weakness was addressed by the choice of a balanced anesthesia protocol without
      the use of muscle-relaxants. Intravenous induction was followed by intubation,
      administration of isoflurane in oxygen and ventilatory support. Thorough
      cardiorespiratory monitoring was performed during anaesthesia. Epidural morphin
      was given to reduce the amount of inhalation agent required to maintain
      anaesthesia and supplemental intravenous analgesia was given. At the end of the
      surgery, intrapleural bupivacaine was administered to help controlling
      poststernotomy pain, while reducing the need for systemic analgesics. Although
      rapid returning of swallowing reflex and spontaneous breathing followed the
      disconnection from the anaesthetic circuit, the cat needed to breath oxygen
      enriched air to maintain a normal hemoglobin saturation in the early
      postoperative phase.

PMID- 18821515
TI  - [Particularities of drug dosing at the beginning and end of therapy].
AB  - The starting dose of a drug determines both onset of action and tolerability of
      the compound. In contrast to most drug therapies, which may immediately be
      started with regular maintenance doses, compounds undergoing substantial
      autoinduction (e.g. carbamazepine) must be administered at slowly increasing
      doses to compensate for an initially low clearance and to avoid toxicity. Gradual
      dose escalation is also necessary whenever a drug induces substantial counter
      regulatory reflex activation or adaptation processes. In these cases
      administration of standard doses may lead to excessive adverse reactions (e.g.
      cardiac decompensation after initiation of beta-receptor antagonism). Also in
      these situations cautious dose titration is required. After long-term
      administration those drugs should be withdrawn only very carefully to avoid
      potentially life-threatening withdrawal syndromes like hypertensive emergencies
      after abrupt discontinuation of clonidine or rebound epilepsies after
      discontinuation of anticonvulsants.

PMID- 18821516
TI  - [Arterial hypertension - dosing recommendations at beginning and end of
      treatment].
AB  - In the treatment of arterial hypertension different dosing strategies like slow
      dose escalation at the beginning of antihypertensive therapy and gradual dose
      taper or abrupt withdrawal of drugs may be appropriate. In general treatment
      should be initiated with a long acting drug at a low dose and doses should only
      slowly be increased under close blood pressure control. The dose-response curve
      usually is very flat, whilst adverse effects may rise disproportionately with
      higher doses. Therefore dose increases to maximal doses are no longer desirable
      in modern antihypertensive therapy and combinations of two drugs as fixed
      combinations at low doses should be preferred. Modern antihypertensive drugs can
      be abruptly and safely withdrawn in most patients. However, a gradual dose taper
      can be necessary in patients with coronary heart disease treated with
      cardioselective beta-blockers. Withdrawal is easier and safer under telemetric
      blood pressure control than self measured blood pressure. The same treatment
      approach applies to reserve medications like alpha-blockers, centrally acting
      drugs as clonidine, methyldopa, moxonidine, the vasodilators hydralazine and
      minoxidil, and other antihypertensives like reserpine and guanethidine.
      Withdrawal phenomena have to be considered in individual cases and particularly
      with clonidine after long-term use.

PMID- 18821517
TI  - [Chronic systolic heart failure - dosing recommendations at beginning and end of
      treatment].
AB  - As a multi-system disease, chronic heart failure requires a complex, multimodal
      therapy. Achieving maximum guideline adherence in (advanced) chronic heart
      failure can therefore become a challenge. The important decrease in morbidity and
      mortality seen lately largely depends on consequent and sometime tedious
      implementation of guideline targets. The present paper provides a comprehensive
      overview on medical therapeutic strategies with a particular focus of onset and
      discontinuation of drugs in patients with chronic systolic dysfunction.

PMID- 18821519
TI  - [Anticoagulation and platelet inhibition - dosing recommendations at the
      beginning and the end of treatment].
AB  - Anticoagulants and anti-platelet drugs are essential and widely used therapeutic
      tools in modern cardiovascular medicine. However, the initiation of anti
      thrombotic therapies, their termination, or transient discontinuation (e.g. for
      surgical procedures) are critical steps which have to be managed appropriately.
      In the near future, several novel irreversibly or reversibly acting anti
      thrombotic drugs with direct and indirect mechanisms of action, will be approved.
      Their prescription will require a deep understanding of their pharmacodynamics
      and -kinetics. In addition, pharmacogenomic issues will become increasingly
      important for the optimization of individual therapeutic strategies. This review
      summarizes clinically relevant principles and discusses them in the light of the
      assessment of the individual thrombotic and bleeding risks.

PMID- 18821518
TI  - [Coronary heart disease and dyslipdemia - dosing recommendations at beginning and
      end of treatment].
AB  - Secondary prevention in patients with coronary heart disease includes treatment
      with platelet inhibitors, beta-blockers, ACE inhibitors or AT (1)-blockers, and
      statins. Initiation of therapy generally does not require a slow gradual dose
      increase. In treatment naive patients with acute coronary syndromes,
      administration of a loading dose of aspirin and/or clopidogrel is recommended. To
      reduce flushing, nicotinic acid should be initiated at low stepwise increasing
      dosages. beta-blocker therapy should not be stopped acutely in coronary heart
      disease patients. If beta-blocker therapy has to be terminated, blood pressure
      should be monitored closely and, if necessary controlled with other medication.
      Termination of statin therapy in the acute phase after strokes or acute coronary
      syndromes is associated with increased cardiovascular events and should therefore
      be avoided.

PMID- 18821520
TI  - [Asthma and COPD - dosing recommendations at beginning and end of treatment].
AB  - In the treatment of asthma and COPD for two drug classes slowly increasing
      starting doses or tapering at the end of therapy is required: In the case of
      allergen specific immunotherapy (desensitisation) with allergen extracts gradual
      increases of doses are necessary to prevent allergic shock. In the case of
      prolonged systemic treatment of asthma or COPD with glucocorticoids tapering is
      necessary to avoid symptoms of adrenal gland insufficiency after drug withdrawal
      or exacerbation of the underlying disease. In the short term treatment of asthma
      exacerbations with systemic glucocorticoids tapering is not necessary, for COPD
      suitable studies are still lacking.

PMID- 18821521
TI  - [Antidepressive therapy - dosing recommendations at beginning and end of
      treatment].
AB  - The knowledge of diagnostic procedures and therapy of depressive disorders is
      very important for every physician because of the high incidence of the disease.
      Particularly with regard to the critical phases of therapy, onset and
      discontinuation of antidepressive medication, a close contact between patient and
      physician is needed to identify adverse effects of the medication and withdrawal
      phenomena. The following article reviews current antidepressants and
      recommendations for starting and stopping antidepressive therapy mainly based on
      clinical experience because only limited evidence-based treatment schedules are
      available.

PMID- 18821522
TI  - [Pain therapy - dosing recommendations at beginning and end of treatment].
AB  - Pain therapy is one of the basic tasks of a clinician. Good knowledge of the
      active profile of prescribed analgesics as well as their side effects will
      facilitate their use and decrease undesired effects. This article discusses
      currently used analgesics, their indication and practical application with
      special consideration of dose requirements at the beginning and end of treatment.

PMID- 18821523
TI  - [Antiepileptic drugs - fast versus slow titration and discontinuation].
AB  - The indication and management of an appropriate therapy with antiepileptic drugs
      (AEDs) requires an individualized diagnostic evaluation considering the clinical
      situation. Based on the current scientific data the therapeutic options and
      special aspects of the available AEDs are discussed with emphasis on the
      possibility of rapid initiation (therapeutic loading doses on day 1) or need of
      slow uptitration over several days or weeks in the context of different clinical
      situations. A sudden discontinuation or withdrawal of AEDs is only justified due
      to life-threatening side effects or for diagnostic purposes in the context of a
      presurgical workup. The debate on the appropriate time for a slow AED
      discontinuation (over a few weeks or several months) is still ongoing.

PMID- 18821524
TI  - Systemic analysis of TGFbeta proteomics revealed involvement of
      Plag1/CNK1/RASSF1A/Src network in TGFbeta1-dependent activation of Erk1/2 and
      cell proliferation.
AB  - Transforming growth factor-beta (TGFbeta) is a key regulator of cell
      proliferation, death, migration, and differentiation. To explore mechanisms of
      TGFbeta action, we performed systemic analysis of functional dependencies between
      153 proteins which changed their expression and synthesis upon treatment of human
      breast epithelial cells with TGFbeta1. We found that TGFbeta1 initiated signaling
      via a scale-free network of proteins which affect primary cellular metabolism,
      stress response, signal transduction, transport, transcription, cytoskeleton, and
      cell death. Multiple inputs into each functional domain were observed,
      emphasizing robustness of TGFbeta1 signaling. Network analysis demonstrated
      importance of a Plag1/CNK1/RASSF1A/Src-dependent prozone effect, as a systemic
      feature which is crucial for TGFbeta1-dependent activation of Erk1/2 and
      regulation of cell proliferation. We showed that the balance between Plag1, CNK1,
      RASSF1A and Src defined whether TGFbeta1 will stimulate, inhibit or will have no
      effect on a long-term activation of Erk1/2 and subsequent TGFbeta1 inhibitory or
      stimulatory effect on cell proliferation. This is the first demonstration of
      importance of systemic features for incorporation of Erk1/2 activation into
      TGFbeta1 signaling.

PMID- 18821525
TI  - Signal transduction pathways of mantle cell lymphoma: a phosphoproteome-based
      study.
AB  - Mantle cell lymphoma (MCL) is an incurable hematologic malignancy whose
      pathogenesis is only partly understood. The aim of the present study was to
      define a "core phosphoproteome" in MCL cell lines that is representative of
      primary MCL in order to improve knowledge of the signal transduction pathways
      involved in its tumorigenesis. We have analyzed phosphorylated proteins in
      several MCL cell lines by immobilized metal affinity chromatography and
      separation by 2-D PAGE, followed by RP-HPLC coupled with MS/MS identification.
      These data were correlated with information on copy number gains obtained by SNP
      chip analysis. Several of the proteins identified could be linked to a specific
      signal transduction pathway, and have been recently recognized as important
      players in MCL pathogenesis, such as nuclear factor-kappaB (NF-kappaB) and
      phosphoinositide-3 kinase-mammalian target of rapamycin (PI3K-mTOR). However, our
      data also implicate a number of novel proteins and pathways in the pathobiology
      of MCL, one of which is mitochondrial signaling. A second-level analysis
      identified MAPK1, CK2, CK1, PKCzeta, and PKCepsilon as candidate upstream
      molecules. Our study provides new insights in MCL pathogenesis and helps to form
      the basis for testing new target-specific therapeutics.

PMID- 18821526
TI  - Intracellular signaling pathways regulating radioresistance of human prostate
      carcinoma cells.
AB  - Radiation therapy plays an important role in the management of prostate
      carcinoma. However, the problem of radioresistance and molecular mechanisms by
      which prostate carcinoma cells overcome cytotoxic effects of radiation therapy
      remains to be elucidated. In order to investigate possible intracellular
      mechanisms underlying the prostate carcinoma recurrences after radiotherapy, we
      have established three radiation-resistant prostate cancer cell lines, LNCaP-IRR,
      PC3-IRR, and Du145-IRR derived from the parental LNCaP, PC3, and Du145 prostate
      cancer cells by repetitive exposure to ionizing radiation. LNCaP-IRR, PC3-IRR,
      and Du145-IRR cells (prostate carcinoma cells recurred after radiation exposure
      (IRR cells)) showed higher radioresistance and cell motility than parental cell
      lines. IRR cells exhibited higher levels of androgen and epidermal growth factor
      (EGF) receptors and activation of their downstream pathways, such as Ras-mitogen
      activated protein kinase (MAPK) and phosphatidyl inositol 3-kinase (PI3K)-Akt and
      Jak-STAT. In order to define additional mechanisms involved in the
      radioresistance development, we determined differences in the proteome profile of
      parental and IRR cells using 2-D DIGE followed by computational image analysis
      and MS. Twenty-seven proteins were found to be modulated in all three
      radioresistant cell lines compared to parental cells. Identified proteins
      revealed capacity to interact with EGF and androgen receptors related signal
      transduction pathways and were involved in the regulation of intracellular routs
      providing cell survival, increased motility, mutagenesis, and DNA repair. Our
      data suggest that radioresistance development is accompanied by multiple
      mechanisms, including activation of cell receptors and related downstream signal
      transduction pathways. Identified proteins regulated in the radioresistant
      prostate carcinoma cells can significantly intensify activation of intracellular
      signaling that govern cell survival, growth, proliferation, invasion, motility,
      and DNA repair. In addition, such analyses may be utilized in predicting cellular
      response to radiotherapy.

PMID- 18821527
TI  - A proteomics study on human breast cancer cell lines by fluorogenic
      derivatization-liquid chromatography/tandem mass spectrometry.
AB  - Although several molecular markers for human breast cancer exist, their
      versatility is limited. Here we demonstrate, through a differential proteome
      analysis utilizing the fluorogenic derivatization-liquid chromatography/tandem
      mass spectrometry (FD-LC-MS/MS) method between seven cancer cells and one normal
      cell, that the presence of cooperatively expressed annexin-2 and galectin-1
      without tropomyosin-1 in a tissue could be used to diagnose metastatic breast
      cancer. Interestingly, in a metastatic cancer cell, the expression of the former
      two together with highly expressed cofilin-1 activates the Rho signal pathway to
      aggressively form disorganized actin filaments. Despite the excess expression of
      annexin-2 and galectin-1 in the normal cell, the highly expressed tropomyosin-1
      counteracted the activity of cofilin-1 and stabilized the filaments, resulting in
      the restoration of the disorganization. This phenomenon suggests that enhancement
      of tropomyosin-1 should be used as therapy for metastatic breast cancer.

PMID- 18821528
TI  - Measuring attachment security in patients with advanced cancer: psychometric
      properties of a modified and brief Experiences in Close Relationships scale.
AB  - OBJECTIVE: Attachment security has been identified as an important buffer of
      distress in patients with cancer and other medical illnesses but current measures
      have not been adapted for this population who may be older, in long-term stable
      relationships, and suffering from considerable disease burden. This study reports
      on (1) the psychometric properties of a modified 36-item Experiences in Close
      Relationships scale (ECR), adapted for this population; and (2) the validity of a
      brief 16-item version of our modified scale. METHODS: A modified ECR (ECR-M36)
      was constructed by rephrasing relevant items to refer more generally to people
      with whom one feels close, instead of specifically in relation to one's romantic
      partner(s). Patients with metastatic gastrointestinal (GI) and lung cancer
      completed the ECR-M36 and other scales tapping self-esteem, social support, and
      depressive symptoms on two occasions within a period of 4-6 months. Based on
      factor analyses of the ECR-M36, 16 items were selected to form a brief measure
      (ECR-M16). RESULTS: Factor analyses of both ECR forms revealed a higher-order
      factor structure in which four first-order factors (Worrying about Relationships,
      Frustration about Unavailability, Discomfort with Closeness, Turning Away from
      Others) loaded onto two second-order factors tapping Attachment Anxiety and
      Avoidance. Both ECR forms were reliable and valid. CONCLUSION: The ECR-M36 and
      ECR-M16 are good measures of attachment orientations for use with medically ill,
      older populations.

PMID- 18821529
TI  - An evidence-based review of yoga as a complementary intervention for patients
      with cancer.
AB  - OBJECTIVE: To conduct an evidence-based review of yoga as an intervention for
      patients with cancer. Specifically, this paper reviewed the impact of yoga on
      psychological adjustment among cancer patients. METHODS: A systematic literature
      search was conducted between May 2007 and April 2008. Data from each identified
      study were extracted by two independent raters; studies were included if they
      assessed psychological functioning and focused on yoga as a main intervention.
      Using a quality rating scale (range = 9-45), the raters assessed the
      methodological quality of the studies, and CONSORT guidelines were used to assess
      randomized controlled trials (RCTs). Effect sizes were calculated when possible.
      In addition, each study was narratively reviewed with attention to outcome
      variables, the type of yoga intervention employed, and methodological strengths
      and limitations. RESULTS: Ten studies were included, including six RCTs. Across
      studies, the majority of participants were women, and breast cancer was the most
      common diagnosis. Methodological quality ranged greatly across studies (range =
      15.5-42), with the average rating (M = 33.55) indicating adequate quality.
      Studies also varied in terms of cancer populations and yoga interventions
      sampled. CONCLUSIONS: This study provided a systematic evaluation of the yoga and
      cancer literature. Although some positive results were noted, variability across
      studies and methodological drawbacks limit the extent to which yoga can be deemed
      effective for managing cancer-related symptoms. However, further research in this
      area is certainly warranted. Future research should examine what components of
      yoga are most beneficial, and what types of patients receive the greatest benefit
      from yoga interventions.

PMID- 18821531
TI  - Synthesis, microwave-assisted polymerization, and polymer properties of
      fluorinated 2-phenyl-2-oxazolines: a systematic study.
AB  - We present a detailed systematic study of the synthesis and ability of
      fluorinated 2-phenyl-2-oxazolines to undergo polymerization. The synthesis of
      these compounds is based on a two-step procedure that gives the desired 2
      oxazolines in moderate-to-good yields. All the compounds were fully characterized
      by IR and NMR ((1)H, (13)C, and (19)F) spectroscopy, mass spectrometry, and
      elemental analysis. The 2-oxazolines were subsequently used as monomers for
      living cationic ring-opening polymerization (CROP) with microwave irradiation as
      the heat source (T=140 degrees C), nitromethane as the solvent, and methyl
      tosylate as the initiator. The linear first-order kinetic plots of the
      polymerizations accompanied by a linear increase of the molecular weight with
      conversion and low polydispersity index (PDI) values (generally below 1.30)
      indicate a living polymerization mechanism. The resulting polymerization rates
      reflect a strong sensitivity to the quantity of fluorine substituents in general
      and the presence or absence of ortho-fluoro substituents of the phenyl ring in
      particular. All the polymers were isolated and characterized by size-exclusion
      chromatography and MALDI-TOF mass spectrometry. Finally, a detailed investigation
      of selected polymer properties was performed by using differential scanning
      calorimetry, thermogravimetric analysis, and contact-angle measurements, thus
      resulting in structure-property relationships. Whereas the thermal properties of
      the polymers are mostly influenced by the presence of ortho-fluoro substituents,
      the surface properties are mainly determined by the presence of para- and/or meta
      fluoro substituents.

PMID- 18821530
TI  - Personality predicts prostate cancer treatment decision-making difficulty and
      satisfaction.
AB  - OBJECTIVE: Prostate cancer (PCa) patients often must decide between several
      treatment modalities considered equally efficacious, but associated with
      different benefits and side-effects. For some, the decision-making process can be
      difficult, but little is known about patient characteristics and cognitive
      processes that might influence the difficulty of such decisions. This study
      investigated the roles of dispositional optimism and self-efficacy in PCa
      treatment decision-making difficulty and satisfaction. METHODS: One hundred and
      twenty-five patients with clinically localized PCa completed a mail-in paper-and
      pencil survey after they had made their treatment decision, but prior to
      treatment. RESULTS: After adjusting for covariates, optimism and treatment
      decision-making self-efficacy were associated with less difficulty and greater
      satisfaction with the treatment decision-making process. Effects of optimism on
      difficulty and satisfaction were partially mediated by self-efficacy for making
      the treatment decision. CONCLUSIONS: Men with PCa and who are low in optimism may
      be at greater risk for treatment decision-making difficulty and lack of treatment
      decision-making satisfaction, in part, because they have lower confidence in
      their ability to make the decision compared with those who are more optimistic.
      As self-efficacy perceptions are modifiable, consideration should be given to
      including self-efficacy enhancing components as part of PCa treatment decision
      making interventions.

PMID- 18821532
TI  - The synthesis of azadirachtin: a potent insect antifeedant.
AB  - We describe in full the first synthesis of the potent insect antifeedant
      azadirachtin through a highly convergent approach. An O-alkylation reaction is
      used to unite decalin ketone and propargylic mesylate fragments, after which a
      Claisen rearrangement constructs the central C8-C14 bond in a stereoselective
      fashion. The allene which results from this sequence then enables a second
      critical carbon-carbon bond forming event whereby the [3.2.1] bicyclic system,
      present in the natural product, is generated via a 5-exo-radical cyclisation
      process. Finally, using knowledge gained through our early studies into the
      reactivity of the natural product, a series of carefully designed steps completes
      the synthesis of this challenging molecule.

PMID- 18821533
TI  - Organocatalytic enantioselective aminosulfenylation of alpha,beta-unsaturated
      aldehydes.

PMID- 18821534
TI  - Triarylphosphanes with dendritically arranged tetraethylene glycol moieties at
      the periphery: an efficient ligand for the palladium-catalyzed Suzuki-Miyaura
      coupling reaction.

PMID- 18821535
TI  - Accurate melting temperatures for neon and argon from ab initio Monte Carlo
      simulations.

PMID- 18821536
TI  - Cobalt-lanthanide coordination polymers constructed with metalloligands: a
      ferromagnetic coupled quasi-1D Dy3+ chain showing slow relaxation.
AB  - Four types of cobalt-lanthanide heterometallic compounds based on metalloligand
      Co(2,5-pydc)(3) (3-) (2,5-H(2)pydc=pyridine-2,5-dicarboxylate acid),
      [Ln(2)Co(2)(2,5-pydc)(6)(H(2)O)(4)](n) 2n H(2)O (1) (Ln=Tb, Dy for 1 a, 1 b
      respectively), [Tb(2)Co(2)(2,5-pydc)(6)(H(2)O)(4)](n)3n H(2)O (2),
      [Tb(2)Co(2)(2,5-pydc)(6)(H(2)O)(9)](n)4n H(2)O (3), and [LaCo(2,5
      pydc)(3)(H(2)O)(2)](n)2n H(2)O (4) have been synthesized. Compound 1 has a layer
      structure with well-isolated carboxylate-bridged Ln(3+) chains, compound 2 is a
      three-dimensional (3D) porous network with Tb(3+) chains that are also well
      isolated and carboxylate bridged, 3 is a layer structure based on dinuclear
      units, and 4 is a 3D network with boron nitride (BN) topology. DC magnetic
      studies reveal ferromagnetic coupling in all the carboxylate-bridged Ln(3+)
      chains in 1 a, 1 b, and 2. Compared to the silence of the out-of-phase ac
      susceptibility of 2, above 1.9 K the magnetic relaxation behavior of both 1 a and
      1 b is slow like that of a single-chain magnet.

PMID- 18821537
TI  - SPOT synthesis of peptide arrays on self-assembled monolayers and their
      evaluation as enzyme substrates.

PMID- 18821538
TI  - CO blocking of D2 dissociative adsorption on Ru(0001).
AB  - The influence of pre-adsorbed CO on the dissociative adsorption of D(2) on
      Ru(0001) is studied by molecular-beam techniques. We determine the initial
      dissociation probability of D(2) as a function of its kinetic energy for various
      CO pre-coverages between 0.00 and 0.67 monolayers (ML) at a surface temperature
      of 180 K. The results indicate that CO blocks D(2) dissociation and perturbs the
      local surface reactivity up to the nearest-neighbour Ru atoms. Non-activated
      sticking and dissociation become less important with increasing CO coverage, and
      vanish at theta(CO) approximately 0.33 ML. In addition, at high D(2) kinetic
      energy (>35 kJ mol(-1)) the site-blocking capability of CO decreases rapidly.
      These observations are attributed to a CO-induced activation barrier for D(2)
      dissociation in the vicinity of CO molecules.

PMID- 18821539
TI  - Europium-doped mesoporous titania thin films: rare-earth locations and emission
      fluctuations under illumination.
AB  - Herein, Eu(III)-doped 3D mesoscopically ordered arrays of mesoporous and
      nanocrystalline titania are prepared and studied. The rare-earth-doped titania
      thin films-synthesized via evaporation-induced self-assembly (EISA)-are
      characterized by using environmental ellipsoporosimetry, electronic microscopy
      (i.e. high-resolution scanning electron microscopy, HR-SEM, and transmission
      electron microscopy, HR-TEM), X-ray diffraction, and luminescence spectroscopy.
      Structural characterizations show that high europium-ion loadings can be
      incorporated into the titanium-dioxide walls without destroying the mesoporous
      arrangement. The luminescence properties of Eu(III) are investigated by using
      steady-state and time-resolved spectroscopy via excitation of the Eu(III) ions
      through the titania host. Using Eu(III) luminescence as a probe, the europium-ion
      sites can be addressed with at least two different environments within the
      mesoporous framework, namely, a nanocrystalline environment and a glasslike one.
      Emission fluctuations ((5)D(0)-->(7)F(2)) are observed upon continuous UV
      excitation in the host matrix. These fluctuations are attributed to charge
      trapping and appear to be strongly dependent on the amount of europium and the
      level of crystallinity.

PMID- 18821540
TI  - Cyano analogues of 7-azaindole: probing excited-state charge-coupled proton
      transfer reactions in protic solvents.
AB  - The interplay between excited-state charge and proton transfer reactions in
      protic solvents is investigated in a series of 7-azaindole (7AI) derivatives: 3
      cyano-7-azaindole (3CNAI), 5-cyano-7-azaindole (5CNAI), 3,5-dicyano-7-azaindole
      (3,5CNAI) and dicyanoethenyl-7-azaindole (DiCNAI). Similar to 7AI, 3CNAI and
      3,5CNAI undergo methanol catalyzed excited-state double proton transfer (ESDPT),
      resulting in dual (normal and proton transfer) emission. Conversely, ESDPT is
      prohibited for 5CNAI and DiCNAI in methanol, as supported by a unique normal
      emission with high quantum efficiency. Instead, the normal emission undergoes
      prominent solvatochromism. Detailed relaxation dynamics and temperature dependent
      studies are carried out. The results conclude that significant excited-state
      charge transfer (ESCT) takes place for both 5CNAI and DiCNAI. The charge-transfer
      specie possesses a different dipole moment from that of the proton-transfer
      tautomer species. Upon reaching the equilibrium polarization, there exists a
      solvent-polarity induced barrier during the proton-transfer tautomerization, and
      ESDPT is prohibited for 5CNAI and DiCNAI during the excited-state lifespan. The
      result is remarkably different from 7AI, which is also unique among most excited
      state charge/proton transfer coupled systems studied to date.

PMID- 18821541
TI  - Pluronics-stabilized gold nanoparticles: investigation of the structure of the
      polymer-particle hybrid.
AB  - Hybrid gold-polymer nanoparticles are obtained by self-assembly of amphiphilic
      copolymers (Pluronics) in solutions containing preformed gold nanoparticles
      (diameter ca. 12 nm). Dynamic light scattering, TEM, cryo-TEM, and small-angle
      neutron scattering experiments with contrast variation are used to characterize
      the structure of the gold-polymer particles. Five Pluronics (F127, F68, F88,
      F108, P84) with different molecular weights and hydrophilic/hydrophobic balances
      are investigated. Gold nanoparticles are individually embedded within globules of
      polymer, even under conditions for which Pluronics micelles do not form in
      solution. The hybrid particles are several tens of nanometers in size (larger
      than micelles of the corresponding Pluronics), and the size can be tuned by
      changing the temperature.

PMID- 18821542
TI  - Host-guest interaction of chaperonin GroEL and water-soluble CdTe quantum dots
      and its size-selective inclusion.
AB  - Some nanoparticles, such as quantum dots (QDs), are widely used in the biological
      and biomedical fields due to their unique optical properties. However, little is
      currently known about the interaction between these nanoparticles and
      biomolecules. Herein, we systemically investigated the interaction between
      chaperonin GroEL and water-soluble CdTe QDs based on fluorescence correlation
      spectroscopy (FCS), capillary electrophoresis, and fluorescence spectrometry. We
      observed that some water-soluble CdTe QDs were able to enter the inner cavity of
      GroEL and formed an inclusion complex after the activation of chaperonin GroEL
      with ATP. The inclusion of GroEL was size-selective to QDs and only small QDs
      were able to enter the inner cavity. The inclusion could suppress the
      fluorescence quenching of the QDs. Meanwhile, we evaluated the association
      constant between chaperonin GroEL and CdTe QDs by FCS. Our results further
      demonstrated that FCS was a very useful tool for study of the interaction of QDs
      and biomolecules.

PMID- 18821543
TI  - Theoretical study on the spectroscopic properties of CO3(*-).nH2O clusters:
      extrapolation to bulk.
AB  - Vertical detachment energies (VDE) and UV/Vis absorption spectra of hydrated
      carbonate radical anion clusters, CO(3)(*-).nH(2)O (n=1-8), are determined by
      means of ab initio electronic structure theory. The VDE values of the hydrated
      clusters are calculated with second-order Moller-Plesset perturbation (MP2) and
      coupled cluster theory using the 6-311++G(d,p) set of basis functions. The bulk
      VDE value of an aqueous carbonate radical anion solution is predicted to be 10.6
      eV from the calculated weighted average VDE values of the CO(3)(*-).nH(2)O
      clusters. UV/Vis absorption spectra of the hydrated clusters are calculated by
      means of time-dependent density functional theory using the Becke three-parameter
      nonlocal exchange and the Lee-Yang-Parr nonlocal correlation functional (B3LYP).
      The simulated UV/Vis spectrum of the CO(3)(*-).8H(2)O cluster is in excellent
      agreement with the reported experimental spectrum for CO(3)(*-) (aq), obtained
      based on pulse radiolysis experiments.

PMID- 18821544
TI  - Solvent-mediated generation of cobalt-cluster-stabilised propargyl cations and
      radicals: allyl migration versus peroxide formation.
AB  - The protonation of [Co(2)(CO)(6){9-[(allyldimethylsilyl)ethynyl]-9H-fluoren-9
      ol}] (4), with HBF(4) in CH(2)Cl(2) led to migration of the allyl group from
      silicon to the cobalt-stabilised cationic site to furnish [Co(2)(CO)(6){9-allyl-9
      [(dimethylfluorosilyl)ethynyl]-9H-fluorene}] (17). However, under the same
      conditions, [Co(2)(CO)(6){9-[(benzyldimethylsilyl)ethynyl]-9H-fluoren-9-ol}] (5)
      underwent desilylation and rearrangement of the resulting terminal alkyne
      dicobalt complex to give [Co(3)(CO)(9)(9H-fluorenylmethylcarbynyl)] (24);
      moreover, dimerisation of the (benzyldimethylsilyl)ethynyl-9H-fluorenyl moiety
      led to the propargyl-allene 26. In contrast, protonation of 5 in THF yielded
      [{Co(2)(CO)(6){[(benzyldimethylsilyl)ethynyl-9H-fluorenyl])}(2)peroxide] (27)
      through a radical coupling process. Analogously, protonation of [Co(2)(CO)(6){9
      [(vinyldimethylsilyl)ethynyl]-9H-fluoren-9-ol}] (6) yields the corresponding
      peroxide 28. X-ray crystallographic data are reported for, among others,
      complexes 17, 24, 26, 27 and 28.

PMID- 18821545
TI  - Reversible conversion of electronic structures in a cyclic octacopper complex.

PMID- 18821546
TI  - Origin of diastereocontrol in the oxy-Michael reactions of delta-lactol anions: a
      computational and experimental study.
AB  - The diastereoselectivity in the alkylation and Michael addition of "naked" 6
      substituted delta-lactolates has been studied by density functional (B3LYP)
      calculations with ab initio (MP2) energy refinements. The resulting proposed
      model for the origins of stereocontrol in this reaction has been tested by
      experiment. The reactions lead to a high cis diastereoselectivity across the THP
      ring due to the preference for both the alkoxide and the 6-substituent to sit
      equatorial in the alkylation transition structure. In the oxy-Michael addition of
      these lactolates to beta-substituted nitroolefins, we propose that the high
      diastereoselectivity beta- to the nitro group is a result of a combination of
      steric, stereoelectronic and solvation factors.

PMID- 18821547
TI  - An NMR investigation of fast proton transfer along the surface of cationic
      micelles.

PMID- 18821548
TI  - Strategies for the improvement of the hydrogen storage properties of metal
      hydride materials.
AB  - Metal hydrides are an important family of materials that can potentially be used
      for safe, efficient and reversible on-board hydrogen storage. Light-weight metal
      hydrides in particular have attracted intense interest due to their high hydrogen
      density. However, most of these hydrides have rather slow absorption kinetics,
      relatively high thermal stability, and/or problems with the reversibility of
      hydrogen absorption/desorption cycling. This paper discusses a number of
      different approaches for the improvement of the hydrogen storage properties of
      these materials, with emphasis on recent research on tuning the ionic mobility in
      mixed hydrides. This concept opens a promising pathway to accelerate
      hydrogenation kinetics, reduce the activation energy for hydrogen release, and
      minimize deleterious possible by-products often associated with complex hydride
      systems.

PMID- 18821549
TI  - Circular dichroism study of the mechanism of formation of DNA templated
      nanowires.
AB  - In order to control the fabrication method, the mechanism used in the formation
      of DNA templated nanowires is investigated through circular dichroism (CD)
      spectroscopy. Metallic (Au) and magnetic (Fe(2)O(3) and CoFe(2)O(4))
      nanoparticles (NP) are aligned along the DNA strand at various mass ratios. The
      DNA templated nanowires are compared to the structure of B-form dsDNA through CD
      experiments. Absorbance and thermal melting tests are performed to verify the
      structural changes of DNA templated nanowires. Low concentrations of
      nanoparticles preserve the DNA B-form through electrostatic interactions.
      Conversely, at higher concentrations of nanoparticles aligned along the DNA
      strand, the template is denatured. Information on the mode of nanoparticle
      binding and DNA helix alterations are explored for metallic and magnetic
      nanowires based upon the results.

PMID- 18821550
TI  - Spin-label EPR on alpha-synuclein reveals differences in the membrane binding
      affinity of the two antiparallel helices.
AB  - The putative function of the Parkinson's disease-related protein alpha-Synuclein
      (alphaS) is thought to involve membrane binding. Therefore, the interaction of
      alphaS with membranes composed of zwitterionic (POPC) and anionic (POPG) lipids
      was investigated through the mobility of spin labels attached to the protein.
      Differently labelled variants of alphaS were produced, containing a spin label at
      positions 9, 18 (both helix 1), 69, 90 (both helix 2), and 140 (C terminus).
      Protein binding to POPC/POPG vesicles for all but alphaS140 resulted in two
      mobility components with correlation times of 0.5 and 3 ns, for POPG mole
      fractions >0.4. Monitoring these components as a function of the POPG mole
      fraction revealed that at low negative-charge densities helix 1 is more tightly
      bound than helix 2; this indicates a partially bound form of alphaS. Thus, the
      interaction of alphaS with membranes of low charge densities might be initiated
      at helix 1. The local binding information thus obtained gives a more
      differentiated picture of the affinity of alphaS to membranes. These findings
      contribute to our understanding of the details and structural consequences of
      alphaS-membrane interactions.

PMID- 18821551
TI  - Design of gold nanoparticle-based colorimetric biosensing assays.
AB  - Gold nanoparticle (AuNP)-based colorimetric biosensing assays have recently
      attracted considerable attention in diagnostic applications due to their
      simplicity and versatility. This Minireview summarizes recent advances in this
      field and attempts to provide general guidance on how to design such assays. The
      key to the AuNP-based colorimetric sensing platform is the control of colloidal
      AuNP dispersion and aggregation stages by using biological processes (or
      analytes) of interest. The ability to balance interparticle attractive and
      repulsive forces, which determine whether AuNPs are stabilized or aggregated and,
      consequently, the color of the solution, is central in the design of such
      systems. AuNP aggregation in these assays can be induced by an "interparticle
      crosslinking" mechanism in which the enthalpic benefits of interparticle bonding
      formation overcome interparticle repulsive forces. Alternatively, AuNP
      aggregation can be guided by the controlled loss of colloidal stability in a
      "noncrosslinking-aggregation" mechanism. In this case, as a consequence of
      changes in surface properties, the van der Waals attractive forces overcome
      interparticle repulsive forces. Using representative examples we illustrate the
      general strategies that are commonly used to control AuNP aggregation and
      dispersion in AuNP-based colorimetric assays. Understanding the factors that play
      important roles in such systems will not only provide guidance in designing AuNP
      based colorimetric assays, but also facilitate research that exploits these
      principles in such areas as nanoassembly, biosciences and colloid and polymer
      sciences.

PMID- 18821552
TI  - The entropy balance of nostocyclopeptide macrocyclization analysed by NMR
      spectroscopy.

PMID- 18821553
TI  - Site-selective and nondestructive protein labeling through azaelectrocyclization
      induced cascade reactions.

PMID- 18821554
TI  - Inhibition of Mycobacterium tuberculosis pantothenate synthetase by analogues of
      the reaction intermediate.

PMID- 18821555
TI  - A novel conformationally constrained parallel g quadruplex.

PMID- 18821556
TI  - Oligosaccharide-mediated nuclear transport of nanoparticles.

PMID- 18821557
TI  - Microfluidic lithography to create dynamic gradient SAM surfaces for spatio
      temporal control of directed cell migration.

PMID- 18821558
TI  - Morphogenesis and crystallization of ZnS microspheres by a soft template-assisted
      hydrothermal route: synthesis, growth mechanism, and oxygen sensitivity.
AB  - Almost monodisperse ZnS microspheres have been synthesized on a large scale by a
      hydrothermal route, in which tungstosilicate acid (TSA) was used as a soft
      template. By controlling the reaction conditions, such as reaction temperature,
      pH value of the solutions, and the reaction medium, almost monodisperse
      microspheres can be synthesized. The structure of these microspheres is sensitive
      to the reaction conditions. The growth mechanism of these nearly monodisperse
      microspheres was examined. Oxygen sensing is realized from ZnS microspheres. The
      current through the ZnS microspheres under UV illumination increases as the
      oxygen concentration decreases.

PMID- 18821559
TI  - Deep desulfurization of fossil fuels by air in the absence of a catalyst.

PMID- 18821560
TI  - Glycerol upgrading over zeolites by batch-reactor liquid-phase oligomerization:
      heterogeneous versus homogeneous reaction.
AB  - Glycerol upgrading to diglycerols in the presence of basic (Na+ or Cs+) ion
      exchanged (FAU or BEA) zeolite catalysts was studied in a liquid-phase batch
      rector at 260 degrees C under normal pressure. Homogeneous NaHCO3 and CsHCO3
      catalysts were studied for comparison. All the catalysts, including NaHCO3 and
      CsHCO3, displayed the same conversion-selectivity relationship. The selectivity
      to linear diglycerols decreased at higher conversions/reaction times owing to the
      consecutive formation of higher oligomers, with preferential further conversion
      of alpha,alpha'-diglycerol. The maximum yield of linear diglycerols was limited
      to about 30 %. The activities of the zeolites followed the order X>Y>Beta,
      independent of the alkali ion present. Catalysis by the zeolites starts with an
      induction period attributed to a slow leaching of alkaline cations from the
      zeolite. Thereafter, the reaction is characterized by a progressive loss of the
      microporous structure of the zeolite and increasing overlap of heterogeneous and
      homogeneous catalysis, where, primarily, the activity depends on the cation
      content of the zeolite.

PMID- 18821561
TI  - Heat of adsorption for hydrogen in microporous high-surface-area materials.

PMID- 18821562
TI  - MicroRNAs in embryonic stem cells.
AB  - The unique properties of embryonic stem cells (ESCs) to self-renew indefinitely
      or to differentiate to any cell type have great potential for clinical
      applications in regenerative medicine. MicroRNAs (miRNAs) are emerging as
      important regulators of post-transcriptional gene expression and have been
      implicated as crucial elements in regulating ESCs. Here, we review recent
      progresses in characterizing the role of miRNAs in the maintenance and
      development of ESCs.

PMID- 18821563
TI  - BAG3 protein regulates caspase-3 activation in HIV-1-infected human primary
      microglial cells.
AB  - BAG3, a member of the BAG co-chaperones family, is expressed in several cell
      types subjected to stressful conditions, such as exposure to high temperature,
      heavy metals, drugs. Furthermore, it is constitutively expressed in some tumors.
      Among the biological activities of the protein, there is apoptosis
      downmodulation; this appears to be exerted through BAG3 interaction with the heat
      shock protein (Hsp) 70, that influences cell apoptosis at several levels. We
      recently reported that BAG3 protein was detectable in the cytoplasm of reactive
      astrocytes in HIV-1-associated encephalopathy biopsies. Here we report that
      downmodulation of BAG3 protein levels allows caspase-3 activation by HIV-1
      infection in human primary microglial cells. This is the first reported evidence
      of a role for BAG3 in the balance of death versus survival during viral
      infection.

PMID- 18821564
TI  - Genome-wide association study of response to methylphenidate in 187 children with
      attention-deficit/hyperactivity disorder.
AB  - We conducted a genome-wide association study of symptom response in an open-label
      study of a methylphenidate transdermal system (MTS). All DNA extraction and
      genotyping was conducted at SUNY Upstate Medical University using the Affymetrix
      Genome-Wide Human SNP Array 6.0. All quality control and association analyses
      were conducted using the software package PLINK. After data cleaning and quality
      control, there were 187 subjects (72% (N = 135) male) with mean age 9.2 +/- 2.0
      years and 319,722 SNPs available for analysis. The most statistically significant
      association (rs9627183 and rs11134178; P = 3 x 10(-6)) fell short of the
      threshold for a genome-wide significant association. The most intriguing
      association among suggestive findings (rs3792452; P = 2.6 x 10(-5)) was with the
      metabotropic glutamate receptor 7 gene (GRM7) as it is expressed in brain
      structures also previously associated with ADHD. Among the 102 available SNPs
      covering previously studied candidate genes, two SNPs within the norepinephrine
      transporter gene (NET, SLC6A2) were significant at P < or = 1 x 10(-2). These
      results should be considered preliminary until replicated in larger adequately
      powered, controlled samples but do suggest that noradrenergic and possibly
      glutaminergic genes may be involved with response to methylphenidate.

PMID- 18821565
TI  - Genome-wide association scan of quantitative traits for attention deficit
      hyperactivity disorder identifies novel associations and confirms candidate gene
      associations.
AB  - Attention deficit hyperactivity disorder (ADHD) is a complex condition with
      environmental and genetic etiologies. Up to this point, research has identified
      genetic associations with candidate genes from known biological pathways. In
      order to identify novel ADHD susceptibility genes, 600,000 SNPs were genotyped in
      958 ADHD proband-parent trios. After applying data cleaning procedures we
      examined 429,981 autosomal SNPs in 909 family trios. We generated six
      quantitative phenotypes from 18 ADHD symptoms to be used in genome-wide
      association analyses. With the PBAT screening algorithm, we identified 2 SNPs,
      rs6565113 and rs552655 that met the criteria for significance within a specified
      phenotype. These SNPs are located in intronic regions of genes CDH13 and GFOD1,
      respectively. CDH13 has been implicated previously in substance use disorders. We
      also evaluated the association of SNPs from a list of 37 ADHD candidate genes
      that was specified a priori. These findings, along with association P-values with
      a magnitude less than 10(-5), are discussed in this manuscript. Seventeen of
      these candidate genes had association P-values lower then 0.01: SLC6A1, SLC9A9,
      HES1, ADRB2, HTR1E, DDC, ADRA1A, DBH, DRD2, BDNF, TPH2, HTR2A, SLC6A2, PER1,
      CHRNA4, SNAP25, and COMT. Among the candidate genes, SLC9A9 had the strongest
      overall associations with 58 association test P-values lower than 0.01 and
      multiple association P-values at a magnitude of 10(-5) in this gene. In sum,
      these findings identify novel genetic associations at viable ADHD candidate genes
      and provide confirmatory evidence for associations at previous candidate genes.
      Replication of these results is necessary in order to confirm the proposed
      genetic variants for ADHD.

PMID- 18821566
TI  - SNPs in dopamine D2 receptor gene (DRD2) and norepinephrine transporter gene
      (NET) are associated with continuous performance task (CPT) phenotypes in ADHD
      children and their families.
AB  - Haplotype-tagging SNP analyses were conducted to identify molecular genetic
      substrates of quantitative phenotypes derived from performance on a Continuous
      Performance Task (CPT). Three hundred sixty-four individuals were sampled from
      152 families ascertained on the basis of at least one child having ADHD.
      Probands, their affected and unaffected siblings, and parents were administered a
      CPT. Four different components of performance were analyzed and tested for
      association with SNPs from 10 candidate genes involved in monoaminergic function.
      After correcting for multiple comparisons and controlling for multiple
      individuals from the same family, significant associations were identified
      between commission errors and SNPs in the DRD2 gene (rs2075654, rs1079596), and
      between reaction time variability and a SNP in the NET gene (rs3785155). These
      findings suggest that commission errors and reaction time variability are
      excellent candidates as ADHD endophenotypes based on previously published
      criteria. Results also shed light on the molecular genetic basis of specific
      processes that may underlie the disorder.

PMID- 18821567
TI  - TeenEARS: development of a pilot assessment battery for cochlear implanted
      adolescents.
AB  - Changes in selection criteria have led to the inclusion of pre-lingually deafened
      adolescents as potential cochlear implant candidates, depending on their degree
      of residual hearing, access to and use of acoustic amplification, use of oral
      communication, and other factors such as motivation and support. Outcomes results
      in adolescents vary widely, and it has become evident that there is a need for a
      test battery that can assess a wide range of skills over time. This article
      presents the development and validation of one such test battery: TeenEARS.
      Eleven tests were assessed for inclusion in the test battery. Consideration was
      given to the ability of the test to measure improvement over time; the fact that
      there needed to be easier and more difficult tests in terms of language,
      communication and listening; the need for closed and open-set assessments; and a
      range of listening tasks: from sounds to conversational language. Data on 23
      adolescents assessed and judgment based on clinical experience resulted in eight
      tests being included in the TeenEARS test battery.

PMID- 18821568
TI  - Comparison of rehabilitation results in deaf patients with and without
      genetically related hearing loss.
AB  - The introduction of prognostic tools to evaluate rehabilitation progress in
      cochlear implant patients (CI patients) is of great importance. The authors
      attempted to verify whether the identified 35delG mutation in the GJB2 gene can
      serve as a valuable indicator for rehabilitation progress of CI patients. A group
      of 51 subjects was studied. Molecular analysis was based on the identification of
      35delG in GJB2. Logopedic assessment was performed with a non-verbal test of
      seven sounds, evaluating detection, discrimination and identification of the
      sounds during the first, third and sixth months after implantation. Results
      indicated that patients with GJB2-related deafness (DFNB1)s achieve better
      results in rehabilitation, but only at the early stages of rehabilitation.
      Prolonged rehabilitation equalised differences, which, subsequently, excluded
      this marker as an indicator for rehabilitation evaluation.

PMID- 18821569
TI  - Late skin flap failure following cochlear implantation.
AB  - The objective of the study was to determine risk factors for late skin flap
      failure following cochlear implantation. The study design was a retrospective
      case series. Data were collated from 371 implanted patients over a ten-year
      period. Of these patients, 1.3 per cent (n = 5) developed late skin flap failure.
      It is concluded that skin flap failure is a significant, though relatively
      uncommon, complication of cochlear implant surgery. What causes flap failure and
      why it should occur in such a variable fashion are still largely unknown, though
      infection undoubtedly plays an important role. The aetiological factors
      associated with flap failure and possible prevention strategies are discussed.

PMID- 18821570
TI  - Discovery to drugs: the peptide pipeline. Proceedings of the Fourth International
      Peptide Symposium. Fall 2007. Cairns, Australia.

PMID- 18821571
TI  - The Fourth International Peptide Symposium: discovery to drugs: the peptide
      pipeline.

PMID- 18821572
TI  - Thrombin induced secretion of macrophage migration inhibitory factor (MIF) and
      its effect on nuclear signaling in endothelium.
AB  - The procoagulant thrombin stimulates endothelial cells (EC) to undergo rapid
      cytoskeleton changes via signaling pathways that induce multiple phenotypic
      changes, including alterations in permeability, vasomotor tone, adhesion molecule
      synthesis, and leukocyte trafficking. We studied a novel role of thrombin's
      action on the endothelium that results in MIF secretion, which is linked to
      myosin light chain (MLC) and extracellular signal-regulated kinase (ERK(1/2))
      dependent nuclear signaling. In bovine pulmonary artery EC (BPAEC), thrombin
      treatment induced intracellular MLC phosphorylation within 15 min, followed by a
      significant increase in MIF secretion within 30 min. Thrombin treatment induced
      biphasic ERK(1/2) phosphorylation with an early phase occurring at 15 min and a
      later phase at 120 min. To understand the role of MIF secretion in thrombin
      induced biphasic activation of ERK(1/2), BPAE cells were treated with (i)
      recombinant MIF, and (ii) the medium collected from thrombin-treated BPAE cells.
      These studies demonstrated a sustained monophasic ERK(1/2) phosphorylation.
      Inhibition of MIF secretion by MIF siRNA or antisense-MIF treatment, along with a
      neutralizing antibody, attenuated the thrombin-induced second phase ERK
      phosphorylation, suggesting a direct involvement of MIF in the second phase of
      ERK(1/2) activation. Pretreatment of BPAE cells with an ERK kinase inhibitor and
      with antisense-MIF significantly inhibited thrombin-induced nuclear factor kappa
      (NF-kappaB) activation. These results indicate that MIF secretion and ERK
      phosphorylation both play a necessary role in thrombin induced NF-kappaB
      activation.

PMID- 18821573
TI  - Isolation and characterization of porcine adult muscle-derived progenitor cells.
AB  - Here, we report the isolation of progenitor cells from pig skeletal muscle tissue
      fragments. Muscle progenitor cells were stimulated to migrate from protease
      digested tissue fragments and cultured in the presence of 5 ng/ml basic
      fibroblast growth factor. The cells showed a sustained long-term expansion
      capacity (>120 population doublings) while maintaining a normal karyotype. The
      proliferating progenitor cells expressed PAX3, DESMIN, SMOOTH MUSCLE ACTIN,
      VIMENTIN, CD31, NANOG and THY-1, while MYF5 and OCT3/4 were only expressed in the
      lower or higher cell passages. Myogenic differentiation of porcine progenitor
      cells was induced in a coculture system with murine C2C12 myoblasts resulting in
      the formation of myotubes. Further, the cells showed adipogenic and osteogenic
      lineage commitment when exposed to specific differentiation conditions. These
      observations were determined by Von Kossa and Oil-Red-O staining and confirmed by
      quantitative RT-PCR analysis. In conclusion, the porcine muscle-derived
      progenitor cells possess long-term expansion capacity and a multilineage
      differentiation capacity.

PMID- 18821574
TI  - Chromosome instability and tumor lethality suppression in carcinogenesis.
AB  - The maintenance and survival of each organism depends on its genome integrity.
      Alterations of essential genes, or aberrant chromosome number and structure lead
      to cell death. Paradoxically, cancer cells, especially in solid tumors, contain
      somatic gene mutations and are chromosome instability (CIN), suggesting a
      mechanism that cancer cells have acquired to suppress the lethal mutations and/or
      CIN. Herein we will discuss a tumor lethality suppression concept based on the
      studies of yeast genetic interactions and transgenic mice. During the early
      stages of the multistep process of tumorigenesis, incipient cancer cells probably
      have adopted genetic and epigenetic alterations to tolerate the lethal mutations
      of other genes that ensue, and to a larger extent CIN. In turn, CIN mediated
      massive gain and loss of genes provides a wider buffer for further genetic
      reshuffling, resulting in cancer cell heterogeneity, drug resistance and evasion
      of oncogene addiction, thus CIN may be both the effector and inducer of
      tumorigenesis. Accordingly, interfering with tumor lethality suppression could
      lead to cancer cell death or growth defects. Further validation of the tumor
      lethality suppression concept would help to elucidate the role of CIN in
      tumorigenesis, the relationship between CIN and somatic gene mutations, and would
      impact the design of anticancer drug development.

PMID- 18821575
TI  - MRI retinovascular studies in humans: research in patients with diabetes.
AB  - PURPOSE: To review existing applications of MRI for detecting blood-retinal
      barrier (BRB) damage and retinal oxygenation response abnormalities in patients
      with diabetes and highlight new information available from such applications.
      METHODS: BRB studies were accomplished using dynamic contrast-enhanced MRI, and
      the retinal oxygenation response studies were accomplished by monitoring changes
      in the MRI signal associated with hyperoxic provocation. Participants were
      patients with diabetes and macular edema, with either no detectable or mild to
      moderate background retinopathy, as well as non-diabetic individuals of similar
      age (controls). Single-slice FLASH images were obtained using a Siemens Sonata,
      1.5 T together with a Siemens 'Loop Small' surface coil fixed in place over the
      eye. Time-dependent changes in image contrast in the pre-retinal vitreous were
      quantified, and differences between patients and controls were assessed
      statistically. RESULTS: The BRB breakdown studies showed a significant difference
      in the temporal evolution of the MRI signal enhancement post-contrast injection
      between the controls and the patients with diabetic macular edema. The retinal
      oxygenation studies revealed a supernormal oxygenation response in the pre
      retinal vitreous in patients with diabetes who had no evidence of retinopathy, as
      well as in patients with background diabetic retinopathy. A nasal-temporal
      asymmetry in the evolution of retinal oxygenation response was found in patients
      with diabetes that was not present in healthy subjects. CONCLUSIONS: These
      studies show that subtle differences in retinovascular function between patients
      with diabetes and non-diabetic individuals, including changes that occur in
      advance of the clinical appearance of diabetic retinopathy, can be detected with
      MRI. These results, together with previous extensive preclinical data, establish
      MRI as a powerful non-invasive method for measuring spatial and temporal changes
      in the same key retinovascular metrics in both animals and humans. Wide
      application of these techniques for diagnosis and evaluation of treatment
      efficacy in a variety of human retinopathies, including diabetic retinopathy, is
      expected.

PMID- 18821576
TI  - Prenylated isoflavones from Flemingia philippinensis.
AB  - Two new prenylated isoflavones, named flemiphilippinins E and F, were isolated
      from the roots of Flemingia philippinensis, together with six known ones. The
      structures of the above compounds were established by spectroscopic methods.
      Flemiphilippinins E and F were identified as 5,4'-dihydroxy-8-(3,3-dimethylallyl)
      6'',6''-dimethyl-5''-(1,1-dimethylallyl) pyrano(2'',3'':7,6)isoflavone and 5,4'
      dihydroxy-4'',4'',5''-trimethyl-4'',5''-dihydrofurano(2'',3'':7,8) isoflavone,
      respectively, by a combination of HR-EI-MS, (1)H NMR, (13)C NMR, HMQC, HMBC, and
      NOESY spectra.

PMID- 18821577
TI  - A questionnaire based review of long-term follow-up programs for survivors of
      childhood cancer in Canada.
AB  - BACKGROUND: Major advances have been made in the treatment of childhood cancer;
      however, survivors of childhood cancer are at increased risk for morbidity and
      mortality. There is little literature regarding available long-term follow-up
      programs for survivors of childhood cancer. PROCEDURE: In March 2007, 16 surveys
      were sent to pediatric hematology/oncology programs across Canada to determine
      what programs were available for survivors of childhood cancer, and the nature of
      such programs. RESULTS: Of 15 participating centers, 13 (87%) have multi
      disciplinary programs for the long-term follow-up of pediatric cancer survivors.
      Research databases were documented in 9/15 (60%) of centers to document late
      effects. Dedicated programs for adult survivors of childhood cancer were
      established in 8/15 (53%) of centers. Access to subspecialty care for survivors
      was rated as quite good. Concerns were raised by many participants about patients
      being lost to follow-up. Respondents indicated that primary care physicians
      appear to be under-represented within dedicated long-term follow-up programs.
      CONCLUSION: Long-term follow-up programs for survivors of childhood cancer are
      available in 87% of Canadian pediatric oncology centers. While programs reported
      good access to care for childhood survivors, many adult survivors of childhood
      cancer have more limited timely access to services and patients are often lost to
      follow-up. New models of care incorporating primary care physicians are necessary
      due to growing numbers of survivors.

PMID- 18821578
TI  - Structure elucidation and 1H/13C NMR spectral assignments of four trabectedin
      related compounds.
AB  - This article presents the structure elucidation of four new compounds, formed
      during the hemisynthetic preparation of trabectedin, an anti-tumor natural
      product from Ecteinascidia turbinata. We report herein on the use of UV, MS and
      NMR spectroscopic data along with (1)H and (13)C spectral assignments obtained by
      means of 1D and 2D homo- and heteronuclear NMR techniques.

PMID- 18821579
TI  - Induction of autophagy in malignant rhabdoid tumor cells by the histone
      deacetylase inhibitor FK228 through AIF translocation.
AB  - Malignant rhabdoid tumors (MRT) exhibit a very poor prognosis because of their
      resistance to chemotherapeutic agents and new therapies are needed for the
      treatment of this cancer. Here, we show that the histone deacetylase (HDAC)
      inhibitor FK228 (depsipeptide) has an antitumor effect on MRT cells both in vitro
      and in vivo. FK228 is a unique cyclic peptide and is among the most potent
      inhibitors of both Class I and Class II HDACs. FK228 inhibited proliferation and
      induced apoptosis in all MRT cell lines tested. Preincubation with the pancaspase
      inhibitor zVAD-fmk did not completely rescue FK228-induced cell death, although
      it did inhibit apoptosis. Transmission electron microscopy (TEM) showed that
      FK228 could stimulate MRT cells to undergo apoptosis, necrosis or autophagy.
      FK228 converted unconjugated microtubule-associated protein light chain 3 (LC3-I)
      to conjugated light chain 3 (LC3-II) and induced localization of LC3 to
      autophagosomes. Apoptosis inducing factor (AIF), which plays a role in caspase
      independent cell death, translocated to the nucleus in response to FK228
      treatment. Moreover, small interfering RNA (siRNA) targeting of AIF prevented the
      morphological changes associated with autophagy and redistribution of LC3 to
      autophagosomes. Disrupting autophagy with chloroquine treatment enhanced FK228
      induced cell death. In vivo, FK228 caused a reduction in tumor size and induced
      autophagy in tumor tissues. Using immunoelectron microscopy, we confirmed AIF
      translocation into the nucleus of FK228-induced autophagic cells in vivo. Thus,
      FK228 is a novel candidate for an antitumor agent for MRT cells.

PMID- 18821580
TI  - Promoter methylation of p16 associated with Helicobacter pylori infection in
      precancerous gastric lesions: a population-based study.
AB  - To investigate the relationship between p16 methylation and Helicobacter pylori
      infection in precancerous gastric lesions, a population-based study was conducted
      in Linqu County, a high-risk area of gastric cancer in China. Methylation status
      of p16 was evaluated by methylation-specific polymerase chain reaction in 920
      subjects with precancerous gastric lesions. H. pylori status was determined by
      13C-urea breath test and the density of H. pylori in biopsy specimens used for
      detecting methylation status was assessed by the modified Giemsa stain. The
      frequency of p16 methylation was significantly higher in subjects with H. pylori
      positive than those with H. pylori negative in each category of gastric lesion
      (p<0.001, respectively). Compared with H. pylori negative, the odds ratios (ORs)
      of p16 methylation were markedly elevated in subjects with H. pylori positive for
      superficial gastritis (OR, 9.45; 95% confidence interval [CI]: 2.94-30.41),
      chronic atrophic gastritis (OR, 15.92; 95%CI: 7.60-33.36), intestinal metaplasia
      (OR, 4.46; 95%CI: 2.44-8.13), indefinite dysplasia (OR, 3.67; 95%CI: 1.90-7.10),
      and dysplasia (OR, 2.48; 95%CI: 1.02-5.99). Moreover, the frequencies of p16
      methylation increased steadily with the severity of H. pylori density in gastric
      mucosa. Compared with H. pylori negative, the OR of p16 methylation was 1.02
      16.13 times higher in subjects with mild H. pylori infection, and 2.69-38.73
      times higher in those with moderate/severe infection, respectively. Our findings
      indicate that p16 methylation was significantly associated with H. pylori
      infection in precancerous gastric lesions, suggesting that H. pylori infection
      could potently induce methylation of p16 CpG island.

PMID- 18821581
TI  - Aberrant methylation of EphA7 in human prostate cancer and its relation to
      clinicopathologic features.
AB  - EphA7 is a member of Eph/ephrins family and play diverse roles in carcinogenesis.
      The aim of our study was to investigate functional and structural alterations of
      EphA7 in prostate cancer and determine if those findings correlate with the
      clinicopathologic features of prostate cancer. Forty-eight prostate carcinomas,
      31 benign prostate hyperplasias, 5 normal prostate tissues and 3 prostate cell
      lines (LNCaP, DU145 and PC-3) were examined with quantitative RT-PCR, methylation
      specific PCR and immunohistochemistry. Downregulation or loss of EphA7 mRNA
      expression was detected in 23 of 48 (47.9%) prostate carcinomas, and 2 of 31
      (6.5%) hyperplasias. Methylation of the EphA7 promoter region was present in 20
      of 48 (41.7%) of carcinomas and 6 of 31 (19.3%) hyperplasias, respectively.
      Immunostaining analysis showed EphA7 protein was absent in 10 of 30 (33.3%)
      carcinoma samples available and 8 of them (80.0%) exhibited hypermethylation. The
      frequency of EphA7 methylation was higher in cancer patients with higher Gleason
      score. Treatment of DU145 cells harboring methylation with 5-aza-2'-deoxycytidine
      reactivated expression of EphA7. Ectopic expression of EphA7 in DU145 cells did
      not suppress cell growth but inhibited colony formation. Our study provides
      evidence that epigenetic inactivation of EphA7 may be involved in prostate
      carcinogenesis.

PMID- 18821582
TI  - The MUC1 oncoprotein as a functional target: immunotoxin binding to alpha/beta
      junction mediates cell killing.
AB  - MUC1, a heavily glycosylated mucin, has generated considerable interest as a
      target for tumor killing because of its overexpression in malignancies. Full
      length MUC1 (MUC1/TM) is proteolytically cleaved after synthesis generating alpha
      and beta subunits, which specifically bind in a noncovalent interaction. Although
      the beta chain remains on the cell surface, the alpha chain binds in an on-and
      off interaction. Most anti-MUC1 antibodies (Abs) described to date recognize
      epitopes within the highly immunogenic alpha-chain tandem repeat. Because the
      alpha-chain is shed, such Abs are sequestered and fail to reach MUC1-expressing
      cells. Immunizing with cDNA encoding MUC1/TM and the spliced MUC1/X isoform from
      which the tandem repeat has been deleted yielded antibodies to the MUC1
      alpha/beta junction. Pseudomonas toxin PE38 linked to polyclonal anti-MUC1
      alpha/beta junction Abs both bound and killed MUC1-positive malignant cells.
      Monoclonal DMC209 binds the MUC1 alpha/beta junction in both MUC1/X and MUC1/TM.
      When injected into SCID mice xenotransplanted with human breast cancer MDA-MB
      231, monoclonal DMC209 showed significant in vivo tumor-suppressive activity. The
      MUC1/X alpha/beta junction presents a biologically-significant target in MUC1
      expressing malignancies because (i) antibodies directed against cell-bound
      alpha/beta junction epitopes reach the intended cellular target, (ii) antibodies
      to junction epitope are internalized into cells, (iii) anti alpha/beta junction
      antibodies can effectively kill high MUC1-expressing cancer cells as antibody
      toxin conjugates and (iv) antibodies targeting the MUC1 cell-bound alpha/beta
      junction results in tumor suppression in vivo. Our results indicate that cell
      bound MUC1 alpha/beta junction, unlike shed alpha chain, represents a highly
      effective moiety for targeting and killing MUC1-expressing malignancies.

PMID- 18821584
TI  - Progressive recruitment of Runx2 to genomic targets despite decreasing expression
      during osteoblast differentiation.
AB  - The mRNAs encoding Runx2, a master osteoblast transcription factor, and its
      target gene Osteocalcin (OC), are commonly used as markers of osteoblast
      differentiation. We found that while OC mRNA levels do indeed increase during
      development of the osteoblast phenotype in MC3T3-E1 cultures, Runx2 mRNA levels
      surprisingly decrease. Neither translational control of Runx2 (based on Western
      analysis) nor regulation of its DNA-binding ability (assessed by electrophoretic
      mobility shift assay) could explain the unexpected opposite patterns of Runx2 and
      OC expression. Instead, a series of chromatin immunoprecipitation (ChIP) assays
      during osteoblast differentiation revealed that early on, when Runx2 protein
      amount and DNA-binding activity are maximal, it is practically absent from the OC
      promoter. At later stages, Runx2 is recruited to the OC promoter while Runx2
      mRNA, protein, and in vitro DNA binding progressively decrease. We also followed
      Runx2 occupancy at a novel genomic target discovered by ChIP-Chip analysis of
      cells in which the OC promoter is maximally occupied. The results revealed that
      Runx2 is recruited to this locus and to the OC promoter with a remarkably similar
      temporal pattern. These observations highlight a mechanism that restrains Runx2
      mediated transcriptional control by confining its access to genomic targets to a
      narrow window of time. The need for such stringent control is consistent with the
      severe consequences of Runx2 over-expression in vivo.

PMID- 18821585
TI  - Leptin signaling in breast cancer: an overview.
AB  - The adipocyte-derived peptide leptin acts through binding to specific membrane
      receptors, of which six isoforms (obRa-f) have been identified up to now. Binding
      of leptin to its receptor induces activation of different signaling pathways,
      including the JAK/STAT, MAPK, IRS1, and SOCS3 signaling pathways. Since the
      circulating levels of leptin are elevated in obese individuals, and excess body
      weight has been shown to increase breast cancer risk in postmenopausal women,
      several studies addressed the role of leptin in breast cancer. Expression of
      leptin and its receptors has been demonstrated to occur in breast cancer cell
      lines and in human primary breast carcinoma. Leptin is able to induce the growth
      of breast cancer cells through activation of the Jak/STAT3, ERK1/2, and/or PI3K
      pathways, and can mediate angiogenesis by inducing the expression of vascular
      endothelial growth factor (VEGF). In addition, leptin induces transactivation of
      ErbB-2, and interacts in triple negative breast cancer cells with insulin like
      growth factor-1 (IGF-1) to transactivate the epidermal growth factor receptor
      (EGFR), thus promoting invasion and migration. Leptin can also affect the growth
      of estrogen receptor (ER)-positive breast cancer cells, by stimulating aromatase
      expression and thereby increasing estrogen levels through the aromatization of
      androgens, and by inducing MAPK-dependent activation of ER. Taken together, these
      findings suggest that the leptin system might play an important role in breast
      cancer pathogenesis and progression, and that it might represent a novel target
      for therapeutic intervention in breast cancer.

PMID- 18821586
TI  - Xenoturbellida: the fourth deuterostome phylum and the diet of worms.
AB  - Since the discovery of the marine worm Xenoturbella bocki in 1915 by Sixten Bock
      and its first published description by Einar Westblad (Westblad,1949, Arkiv
      Zoologi 1:3-29), Xenoturbella was generally allied to the turbellarian flatworms,
      perhaps most closely to acoelomorphs. In 1997, however, analyses of ribosomal DNA
      (Noren and Jondelius, 1997, Nature 390:31-32) and developing oocytes (Israelsson,
      1997, Nature 390:32) [and, subsequently, embryos (Israelsson, 1999, Proc R Soc
      Lond B 266:835-841)] recovered from Xenoturbella specimens led to the surprising
      conclusion that it was in fact a highly degenerate bivalve mollusc. Bourlat et
      al. showed in 2003 that this result was due to contamination from bivalves in its
      diet (Bourlat et al.,2003, Nature 424:925-928). Our analyses showed Xenoturbella
      is a deuterostome, related to the Ambulacraria (echinoderms and hemichordates).
      Subsequent work has shown that Xenoturbellida is a separate lineage from the
      Ambulacraria and therefore constitutes the fourth deuterostome phylum (Bourlat et
      al.,2006, Nature 444:85-88). I consider this phylogenetic position in the light
      of what is known of its genetics, morphology, and ontogeny. I examine what this
      phylogenetic position for Xenoturbella can tell us about its own evolution and
      what light this might shine on the common ancestor of the deuterostomes and hence
      on the origins of the chordates.

PMID- 18821587
TI  - The G protein-coupled receptor G2A: involvement in hepatic lipid metabolism and
      gallstone formation in mice.
AB  - The G2A receptor is a member of the ovarian cancer G protein-coupled receptor 1
      family of stress-inducible G protein-coupled receptors. In this study, we
      examined the hepatobiliary effects of loss of function of G2A in mice fed either
      a chow or lithogenic diet. G2A-deficient (G2A(-/-)) mice fed chow had a 25%
      reduction in biliary phosphatidylcholine content, reduced hepatic gene expression
      of the phosphatidylcholine transporter adenosine triphosphate-binding cassette
      B4, and an 8-fold increase in expression of the nuclear receptor liver X receptor
      (LXR). Despite the increased expression of LXR, transcription of several LXR
      target genes was reduced. G2A(-/-) mice fed a lithogenic diet had rapid gallstone
      formation, an increased cholesterol saturation index, a 2.5-fold increase in
      farnesoid X receptor expression, a 5-fold increase in LXR expression, and a 90%
      reduction in cholesterol 7alpha-hydroxylase expression in comparison with wild
      type mice. There were no changes in gallbladder volume. CONCLUSION: These data
      demonstrate that the G2A receptor is important for hepatobiliary bile salt,
      cholesterol, and phospholipid homeostasis and for the pathogenesis of cholesterol
      gallstone formation.

PMID- 18821588
TI  - Interventional treatment should be incorporated in the algorithm for the
      management of patients with portal vein thrombosis.

PMID- 18821589
TI  - Generation of mice with conditionally activated transforming growth factor beta
      signaling through the TbetaRI/ALK5 receptor.
AB  - We generated a transgenic mouse strain (LSL-TbetaRI(CA)) containing a latent
      constitutively active TGFbeta type I receptor (TbetaRI/ALK5) by using a knock-in
      strategy into the X chromosome-linked hypoxanthine phosphoribosyl-transferase
      (Hprt) locus. Transgene expression, under the control of the ubiquitous CAG
      (human cytomegalovirus enhancer and chicken beta-actin) promoter, is repressed by
      a floxed transcriptional "Stop" (LSL, Lox-Stop-Lox). In the presence of cre
      recombinase, the "Stop" is excised to allow TbetaRI(CA) transgene expression. We
      showed that restricted expression of TbetaRI(CA) in T lymphocytes efficiently
      activates TGFbeta signaling and rescues the T-cell autoimmune disorders of
      TGFbetaRII conditional knockouts. Unexpectedly, our study reveals that TGFbeta
      signaling upregulation controls T-cell activation but does not impair their
      development or their peripheral homeostasis. In addition to the information
      provided on TGFbeta effects on T-cell biology, LSL-TbetaRI(CA) mouse constitutes
      an attractive tool to address the effect of TGFbeta signaling upregulation in any
      cell type expressing the cre-recombinase.

PMID- 18821590
TI  - Translational research in liver disease.

PMID- 18821591
TI  - Molecular targeted therapies in hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is a complex and heterogeneous tumor with several
      genomic alterations. There is evidence of aberrant activation of several
      signaling cascades such as epidermal growth factor receptor (EGFR),
      Ras/extracellular signal-regulated kinase, phosphoinositol 3-kinase/mammalian
      target of rapamycin (mTOR), hepatocyte growth factor/mesenchymal-epithelial
      transition factor, Wnt, Hedgehog, and apoptotic signaling. Recently a multikinase
      inhibitor, sorafenib, has shown survival benefits in patients with advanced HCC.
      This advancement represents a breakthrough in the treatment of this complex
      disease and proves that molecular therapies can be effective in HCC. It is
      becoming apparent, however, that to overcome the complexity of genomic
      aberrations in HCC, combination therapies will be critical. Phase II studies have
      tested drugs blocking EGFR, vascular endothelial growth factor/platelet-derived
      growth factor receptor, and mTOR signaling. No relevant data has been produced so
      far in combination therapies. Future research is expected to identify new
      compounds to block important undruggable pathways, such as Wnt signaling, and to
      identify new oncogenes as targets for therapies through novel high-throughput
      technologies. Recent guidelines have established a new frame for the design of
      clinical trials in HCC. Randomized phase II trials with a time-to-progression
      endpoint are proposed as pivotal for capturing benefits from novel drugs.
      Survival remains the main endpoint to measure effectiveness in phase III studies.
      Patients assigned to the control arm should receive standard-of-care therapy,
      that is, chemoembolization for patients with intermediate-stage disease and
      sorafenib for patients with advanced-stage disease. Biomarkers and molecular
      imaging should be part of the trials, in order to optimize the enrichment of
      study populations and identify drug responders. Ultimately, a molecular
      classification of HCC based on genome-wide investigations and identification of
      patient subclasses according to drug responsiveness will lead to a more
      personalized medicine.

PMID- 18821592
TI  - The medaka sex-determining gene DMY acquired a novel temporal expression pattern
      after duplication of DMRT1.
AB  - The male sex-determining gene, DMY, of the medaka is considered to have arisen
      via gene duplication of DMRT1. In the medaka, both genes are expressed in Sertoli
      cell lineage cells, but their temporal expression patterns are quite different.
      DMY expression starts just before the sex-determining period, whereas DMRT1
      expression occurs during the testicular differentiation period. To evaluate the
      alterations to the expression patterns of the DMRT1 genes after duplication, we
      analyzed the morphological gonadal sex differentiation processes and expression
      patterns of DMRT1 in Oryzias luzonensis and Oryzias mekongensis, which are
      closely related to the medaka but do not have DMY. Male-specific upregulation of
      DMRT1 in these two species occurred during the testicular differentiation period,
      similar to the case for DMRT1 in the medaka. These findings suggest that DMY
      acquired a novel temporal expression pattern after duplication and that this
      event played a critical role in the evolutionary process of this gene.

PMID- 18821593
TI  - Hepatitis C is a predictor of acute liver injury among hospitalizations for
      acetaminophen overdose in the United States: a nationwide analysis.
AB  - Acute liver injury (ALI) following acetaminophen overdose (AO) occurs in less
      than 10% of cases, but that risk is increased among alcoholics and those with
      chronic alcoholic liver disease. We sought to assess whether coexistent hepatitis
      C virus (HCV) infection potentiated the hepatotoxic effects of acetaminophen. We
      queried the Nationwide Inpatient Sample (1998-2005), a 20% sample of U.S.
      hospitals, to identify admissions for AO using International Classification of
      Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes. Outcomes were
      development of ALI (ICD-9-CM: 570.0, 572.2, 573.3), in-hospital mortality, severe
      liver failure, and resource utilization. There were 42,781 admissions for AO in
      the sample, yielding a national estimate of 210,436 AO hospitalizations. HCV
      prevalence increased from 0.5% to 1.5% between 1998 and 2005 (P < 0.0001). The
      rate of ALI was 7.2%. After adjusting for confounders and excluding patients with
      cirrhosis, the risk of ALI increased with HCV (adjusted odds ratio [aOR] 1.80;
      95% confidence interval [CI]: 1.30-2.48), nonalcoholic fatty liver disease (aOR
      7.43; 95% CI: 3.30-16.7), alcoholic liver disease (aOR 6.46; 95% CI: 4.53-9.21),
      and malnutrition (aOR 3.84; 95% CI: 2.61-5.65). HCV was associated with greater
      risk of progression to severe liver failure (aOR 3.55; 95% CI: 1.88-6.70). Crude
      mortality was higher in patients with HCV compared to those without HCV (2.1%
      versus 0.9%, P = 0.01); patients with ALI had an overall mortality of 8.6%.
      Length of stay was longer in patients with HCV (4.0 versus 2.6 days, P < 0.0001).
      Admissions with coexistent HCV also incurred two-fold higher hospital charges
      than those that did not ($21,400 versus $11,400, P < 0.0001). CONCLUSION: Our
      retrospective analysis suggests that patients with HCV may be at increased risk
      of ALI following AO. These findings warrant further confirmation in prospective
      studies.

PMID- 18821594
TI  - Dr. H. Butt tribute.

PMID- 18821595
TI  - Rapid diagnosis of Wilson disease in acute liver failure: no more waiting for the
      ceruloplasmin level?

PMID- 18821596
TI  - Intestinal dendritic cells and epithelial barrier dysfunction in Crohn's disease.
AB  - Crohn's disease (CD) is a chronic gastrointestinal inflammatory disorder
      considered to be the result of an inappropriate and exaggerated mucosal immune
      reaction to yet undefined triggers from the gut flora in genetically predisposed
      individuals. This inflammatory phenomenon has been characterized by an adaptive T
      cell response in addition to an abnormal function of the innate immune system.
      Dendritic cells (DCs) are constituents of this innate system, inducing T-cell
      activation via antigen presentation. In the gut, mucosal DCs are separated from
      the luminal milieu by a monolayer of cylindrical epithelial cells that forms an
      anatomical and physiological barrier that controls the normal traffic of antigens
      between both compartments. An imbalance of colonic and ileal DC distribution in
      tissues from CD patients as well as functional differences between DCs isolated
      from normal and diseased intestinal samples have been demonstrated. Moreover, a
      gut barrier defect in the para- and transepithelial routes in addition to a
      significant reduction in the intestinal secretion of epithelial products involved
      in barrier function has been well documented in CD. Therefore, this may expose
      the diseased mucosa to overwhelming amounts of antigens, resulting in abnormal DC
      activation and a subsequent imbalance in their distribution. In conclusion, this
      review provides a summary of relevant progress in CD, intestinal epithelial
      permeability, and DCs highlighting a potential relationship between increased
      epithelial permeability and abnormal DC distribution during the pathogenesis of
      intestinal inflammation.

PMID- 18821597
TI  - Genetic and phenotypic studies of the dark-like mutant mouse.
AB  - The dark-like (dal) mutant mouse has a pleiotropic phenotype that includes dark
      dorsal hairs and reproductive degeneration. Their pigmentation phenotype is
      similar to Attractin (Atrn) mutants, which also develop vacuoles throughout the
      brain. In further characterizing the testicular degeneration of dal mutant males,
      we found that they had reduced serum testosterone and developed vacuoles in their
      testes. Genetic crosses placed dal upstream of the melanocortin 1 receptor (Mc1r)
      and downstream of agouti, although dal suppressed the effect of agouti on
      pigmentation but not body weight. Atrn(mg-3J) and dal showed additive effects on
      pigmentation, testicular vacuolation, and spongiform neurodegeneration, but
      transgenic overexpression of Attractin-like-1 (Atrnl1), which compensates for
      loss of ATRN, did not rescue dal mutant phenotypes. Our results suggest dal and
      Atrn function in the same pathway and that identification of the dal gene will
      provide insight into molecular mechanisms of vacuolation in multiple cell types.

PMID- 18821598
TI  - Lentiviral integration preferences in transgenic mice.
AB  - Lentiviral gene transfer has a significant impact on the development of
      biomedical research. One of the most important features of lentiviruses is the
      capability to infect both dividing and nondividing cells. However, little is
      known whether integration preference exists, specifically in early embryos. An in
      depth genome analysis on 112 independent lentiviral integration sites from 43
      transgenic founder mice was performed to determine if there are preferable sites
      for lentiviral integration in early embryonic genome. Our results demonstrated
      that lentiviruses were biased in integrating within intragenic regions,
      especially in the introns. However, no integration preference was found
      associated with specific chromosomes, repetitive elements, or CpG islands, nor
      was there any preference for integrating at close proximity to transcription
      start sites. Our findings suggested that lentiviruses were biased to integrate
      into the intragenic regions of early embryonic genome of mouse.

PMID- 18821600
TI  - Reactive hyperemia and BOLD MRI demonstrate that VEGF inhibition, age, and
      atherosclerosis adversely affect functional recovery in a murine model of
      peripheral artery disease.
AB  - PURPOSE: To develop magnetic resonace imaging (MRI) methods for functional
      assessment of arteriogenesis in a murine model of peripheral artery disease to
      quantify the influences of vascular endothelial growth factor (VEGF), age, and
      atherosclerosis. MATERIALS AND METHODS: Reactive hyperemia (RH), which was
      induced using a device designed for remote and transient occlusion of the aorta
      and vena cava, was measured by blood-oxygen-level-dependent MRI. Twenty-eight
      days after femoral artery ligation, peak height (PH) and time to peak (TTP) of
      the RH response was compared with sham-operated animals in 10-week-old C57Bl6, 9
      month-old C57Bl6, and 9-month-old Ldlr(-/-)Apobec(-/-) mice. The contribution of
      VEGF to functional recovery was assessed in young mice. Angiogenesis was
      quantified using an anti-PECAM1 radioimmunoassay. RESULTS: In young animals,
      angiogenesis was maximal 7 days after ligation, whereas functional recovery took
      28 days. Inhibition of VEGF eliminated the angiogenesis seen at 7 days and
      reduced RH (PH, P < 0.05). At day 28, RH was altered in old (TTP, P < 0.05) and
      atherosclerotic (PH, P < 0.05; TTP, P < 0.05) animals. RH was different in young,
      old, and atherosclerotic sham animals. Old and atherosclerotic mice showed
      reduced angiogenesis. CONCLUSION: The method presented herein can provide a
      sensitive assay for the functional assessment of arteriogenesis and highlights
      the contribution of VEGF, age, and atherosclerosis to this process.

PMID- 18821601
TI  - Specific absorption rate studies of the parallel transmission of inner-volume
      excitations at 7T.
AB  - PURPOSE: To investigate the behavior of whole-head and local specific absorption
      rate (SAR) as a function of trajectory acceleration factor and target excitation
      pattern due to the parallel transmission (pTX) of spatially tailored excitations
      at 7T. MATERIALS AND METHODS: Finite-difference time domain (FDTD) simulations in
      a multitissue head model were used to obtain B(1) (+) and electric field maps of
      an eight-channel transmit head array. Local and average SAR produced by 2D-spiral
      trajectory excitations were examined as a function of trajectory acceleration
      factor, R, and a variety of target excitation parameters when pTX pulses are
      designed for constant root-mean-square excitation pattern error. RESULTS: Mean
      and local SAR grow quadratically with flip angle and more than quadratically with
      R, but the ratio of local to mean SAR is not monotonic with R. SAR varies greatly
      with target position, exhibiting different behaviors as a function of target
      shape and size for small and large R. For example, exciting large regions
      produces less SAR than exciting small ones for R >or=4, but the opposite trend
      occurs when R <4. Furthermore, smoother and symmetric patterns produce lower SAR.
      CONCLUSION: Mean and local SAR vary by orders of magnitude depending on
      acceleration factor and excitation pattern, often exhibiting complex,
      nonintuitive behavior. To ensure safety compliance, it seems that model-based
      validation of individual target patterns and corresponding pTX pulses is
      necessary.

PMID- 18821602
TI  - Perfusion-weighted magnetic resonance imaging patterns of hypoxic-ischemic
      encephalopathy in term neonates.
AB  - PURPOSE: To determine whether an early magnetic resonance imaging (MRI) study
      using perfusion-weighted imaging (PWI) may define the pattern of brain injury in
      term neonatal hypoxic-ischemic (HI) encephalopathy. MATERIALS AND METHODS: Five
      newborns with HI encephalopathy or a marker of perinatal depression, and 2
      controls underwent an early MRI (at 2 to 4 days), including PWI. Relative
      cerebral blood flow (rCBF) values were measured. RESULTS: On early (<or=4 days)
      PWI-MRI, marked hyperperfusion was seen in areas of HI brain damage, allowing the
      classification of the children into different patterns according to the
      predominant site of injury: 1 with a "normal pattern"; 1 with a "watershed
      pattern" with increased rCBF ratios in white matter; 1 with a "basal ganglia
      pattern" with increased rCBF ratios in basal ganglia; and 2 with a "total
      cortical pattern" with increased rCBF ratios in cortical gray matter, white
      matter, and basal ganglia. These patterns were confirmed in all infants on late
      (9 to 11 days) conventional MRI (T2-weighted images) (4 of 5 patients) or on
      postmortem examination (1 of 5 patients). CONCLUSION: PWI is technically feasible
      in neonates with HI encephalopathy in a reproducible way, permitting comparisons
      between children. It provides a practical means to identify early after birth the
      future definitive ischemic areas that may be shown on conventional MRI only
      later.

PMID- 18821603
TI  - Evaluation of referenceless thermometry in MRI-guided focused ultrasound surgery
      of uterine fibroids.
AB  - PURPOSE: To clinically assess a previously described method (Rieke et.al., Magn
      Reson Med 2004) to produce more motion-robust MRI-based temperature images using
      data acquired during MRI-guided focused ultrasound surgery (MRgFUS) of uterine
      fibroids. MATERIALS AND METHODS: The method ("referenceless thermometry") uses
      surface fitting in nonheated regions of individual phase images to extrapolate
      and then remove background phase variations that are unrelated to temperature
      changes. We tested this method using images from 100 sonications selected from 33
      patient MRgFUS treatments. Temperature measurements and thermal dose contours
      estimated with the referenceless method were compared with those produced with
      the standard phase-difference technique. Fitting accuracy and noise level were
      also measured. RESULTS: In 92/100 sonications, the difference between the two
      measurements was less than 3 degrees C. The average difference in the
      measurements was 1.5 +/- 1.4 degrees C. Small motion artifacts were observed in
      the phase-difference imaging when the difference was greater than 3 degrees C.
      The method failed in two cases. The mean absolute error in the surface fit in
      baseline images corresponded to a temperature error of 0.8 +/- 1.4 degrees C. The
      noise level was approximately 40% lower than the phase-difference method. Thermal
      dose contours calculated from the two methods agreed well on average. CONCLUSION:
      Based on the small error when compared with the standard technique, this method
      appears to be adequate for temperature monitoring of MRgFUS in uterine fibroids
      and may prove useful for monitoring temperature changes in moving organs.

PMID- 18821604
TI  - In vivo (1)H magnetic resonance spectroscopy of amniotic fluid and fetal lung at
      1.5 T: technical challenges.
AB  - PURPOSE: To identify the major technical challenges associated with in utero
      single-voxel proton spectroscopy of amniotic fluid and fetal lung and to evaluate
      the feasibility of performing in utero fetal spectroscopy for fetal lung maturity
      testing. MATERIALS AND METHODS: Fetal magnetic resonance (MR) spectroscopy of
      amniotic fluid and fetal lung were performed at 1.5 T in 8 near-term pregnant
      women. Presence/absence of lactate and choline peaks was tabulated. Ex vivo
      spectra were obtained from amniotic fluid samples to investigate and refine
      sequence parameters. RESULTS: Spectroscopy failed in 3 of 8 cases due to maternal
      discomfort (n = 1) or fetal gastroschisis (n = 2). Both fetal motion and low
      signal-to-noise ratio were limiting factors for the remaining 5 clinical in vivo
      studies at 1.5 T. Ex vivo and in vivo studies suggested feasibility for detecting
      lactate from amniotic fluid within a reasonable clinical scan time (4-5 minutes).
      Lactate was detected in 3 of 5 patients. Choline detection was limited and was
      detected in 1 patient. CONCLUSION: Minor motion effects can be overcome but
      continuous fetal motion is problematic. Lactate detection seems clinically
      feasible, but choline detection requires additional technical development and,
      potentially, further imaging at a higher field strength because of the low signal
      to-noise ratio at 1.5 T.

PMID- 18821606
TI  - Tell me it ain't so: patient-to-patient transmission of hepatitis C in an
      endoscopy clinic.
AB  - On January 2, 2008, the Nevada State Health Division (NSHD) contacted CDC
      concerning surveillance reports received by the Southern Nevada Health District
      (SNHD) regarding two persons recently diagnosed with acute hepatitis C. A third
      person with acute hepatitis C was reported the following day. This raised
      concerns about an outbreak because SNHD typically confirms four or fewer cases of
      acute hepatitis C per year. Initial inquiries found that all three persons with
      acute hepatitis C underwent procedures at the same endoscopy clinic (clinic A)
      within 35-90 days of illness onset. A joint investigation by SNHD, NSHD, and CDC
      was initiated on January 9, 2008. The epidemiologic and laboratory investigation
      revealed that hepatitis C virus (HCV) transmission likely resulted from reuse of
      syringes on individual patients and use of single-use medication vials on
      multiple patients at the clinic. Health officials advised clinic A to stop unsafe
      injection practices immediately, and approximately 40,000 patients of the clinic
      were notified about their potential risk for exposure to HCV and other bloodborne
      pathogens. This report focuses on the six cases of acute hepatitis C identified
      during the initial investigation, which is ongoing; additional cases of acute
      hepatitis C associated with exposures at clinic A might be identified.
      Comprehensive measures involving viral hepatitis surveillance, health-care
      provider education, public awareness, professional oversight, licensing, and
      improvements in medical devices can help detect and prevent transmission of HCV
      and other bloodborne pathogens in health-care settings.

PMID- 18821605
TI  - In vivo estimation and repeatability of force-length relationship and stiffness
      of the human achilles tendon using phase contrast MRI.
AB  - PURPOSE: To devise a method using velocity encoded phase contrast MRI and MR
      compatible dynamometry, for in vivo estimation of elastic properties of the human
      Achilles tendon and to assess within-session and day-to-day repeatability of this
      technique. MATERIALS AND METHODS: Achilles tendon force and calcaneus-movement
      adjusted displacement were measured during a submaximal isometric plantarflexion
      in 4 healthy subjects, four repeated trials each. The measured force-length (F-L)
      relationship was least-squares fitted to a cubic polynomial. Typical error was
      calculated for tendon displacement at multiple force levels, stiffness from the
      "linear region," and transition point from the displacement point separating the
      linear and nonlinear parts of the curve. RESULTS: Displacements of the tendon
      were determined up to a maximum force of 500 N, with mean stiffness of 234 +/- 53
      N/mm, mean transition point of 2.70 +/- 0.23 mm and maximum tendon displacement
      of 3.38 mm. Variability of tendon displacement was not dependent on the force
      level. Overall typical errors were 0.09 mm and 0.16 mm for within-session and
      between days, respectively. Typical error of transition point was 0.05 mm and
      0.14 mm. Stiffness had typical errors of 47.24 N/mm and 51.95 N/mm. The tendon
      cross-sectional area and calcaneus displacement were found to be very significant
      factors in minimizing the individual differences in F-L curves. CONCLUSION: The
      method yielded F-L relationships, stiffness, and transition point values that
      showed good within and day-to-day repeatability. The technique compared well with
      the more conventional one using ultrasonography. Its reliability indicates
      potential for measuring tendon structural changes after an injury, disease, and
      altered loading.

PMID- 18821607
TI  - USPIO (Ferumoxtran-10)-enhanced MRI to visualize reticuloendothelial system cells
      in neonatal rats: feasibility and biodistribution study.
AB  - PURPOSE: To investigate whether USPIO-enhanced magnetic resonance imaging (MRI)
      detected reticuloendothelial system (RES) cells in newborn normal rats. MATERIALS
      AND METHODS: Newborn normal rats were imaged in vivo on a 1.5 T MR system, 2-96
      hours after intraperitoneal Ferumoxtran-10 (n = 38) or saline injection (control
      group, n = 5). Signals from liver, spleen, and vertebral bone marrow were
      measured (T2-weighted Turbo Spin Echo) to describe the kinetics of enhancement.
      The pups were sacrificed and iron concentrations in plasma and peritoneal fluid
      were measured using atomic absorption spectrometry. Prussian blue-labeled cells
      density in liver, spleen, and vertebral bone marrow was assessed. RESULTS:
      Significant (P < 0.05) negative enhancement of the liver, spleen, and vertebral
      bone marrow was noted after Ferumoxtran-10 injection (2-96 hours for liver and
      spleen, 4-96 hours for bone marrow). Ferumoxtran-10 was absorbed from the
      peritoneum in the first 8 hours postinjection, entering the circulation with a
      plasma peak (8 hours); then Ferumoxtran-10 returned over the baseline in plasma
      (96 hours). Important intracellular iron deposition in liver and spleen was
      measured postinjection (3-96 hours, P < 0.05). Limited but significant
      intracellular iron deposition was noted in vertebral bone marrow postinjection
      (96 hours, P < 0.05), suggesting that Ferumoxtran-10 selectively labeled RES
      cells after 96 hours and produced nonspecific labeling at earlier timepoints.
      CONCLUSION: Ferumoxtran-10-enhanced MRI visualizes RES cells in vivo in newborn
      rats.

PMID- 18821609
TI  - Dynamic perfusion MRI: capability for evaluation of disease severity and
      progression of pulmonary arterial hypertension in patients with connective tissue
      disease.
AB  - PURPOSE: To prospectively evaluate the capability of dynamic perfusion MRI for
      assessment of disease severity and progression to pulmonary arterial hypertension
      (PAH) in connective tissue disease (CTD) patients. MATERIALS AND METHODS: In all,
      18 gender- and age-matched CTD patients without and with PAH and nine healthy
      volunteers underwent dynamic perfusion MRI, Doppler echocardiography, and
      pulmonary function test. Disease severity of CTD was assessed in terms of
      diffusing capacity for carbon monoxide (%DL(CO)) and estimated systolic pulmonary
      arterial pressure (sPAP), and progression of PAH in terms of pulmonary arterial
      pressure (mPAP) and pulmonary vascular resistance (PVR). From calculated
      pulmonary perfusion parameter maps, means of pulmonary blood flow (mPBF),
      pulmonary blood volume (mPBV), and mean transit time (mMTT) were determined as
      averages of all region of interest (ROI) measurements. To determine disease
      severity in CTD, all parameters were statistically correlated with sPAP and
      %DL(CO). To determine progression to PAH, all parameters were statistically
      correlated with mPAP and PVR. RESULTS: All pulmonary perfusion parameters
      correlated significantly with sPAP and % DL(CO) (P < 0.05). mPBF and mPBV
      correlated significantly with mPAP and moderately with PVR (P < 0.05).
      CONCLUSION: Dynamic perfusion MRI can be used for assessment of disease severity
      and progression of PAH in CTD patients.

PMID- 18821610
TI  - Initial clinical experience with a new MRI vacuum-assisted breast biopsy device.
AB  - PURPOSE: To report initial clinical experience with a new previously unreported
      vacuum-assisted device (EnCor MR, SenoRx, Aliso Viejo, CA) for magnetic resonance
      imaging (MRI)-guided breast biopsy and to compare this device with previously
      reported technologies. MATERIALS AND METHODS: A prospective study of MRI-guided
      vacuum-assisted breast biopsies using the EnCor device was undertaken. Lesions
      targeted for biopsy were occult on mammography, ultrasound, and physical
      examination. Histologic results were obtained for all cases. Patients with
      benign, concordant results underwent clinical and imaging follow-up. Cases with
      discordant, high-risk, or malignant results were referred for surgical biopsy.
      RESULTS: A total of 55 biopsies were performed in 47 patients. All biopsies were
      technically successful. Histologic results yielded malignancy in 10 (10/55, 18%)
      of the 55 lesions and high-risk or atypical lesions in 7 (7/55, 13%) of the
      cases. All of these patients have had surgical follow-up, with four (4/55, 7%)
      underestimations. There were three (3/55, 5%) discordant cases. 35 (35/55, 64%)
      lesions yielded benign concordant results. Of these, six (6/35, 17%) lesions were
      removed surgically, with confirmation of the MR-guided biopsy results. Twenty
      (20/35, 57%) lesions have undergone at least 6-month follow-up MRI, with
      resolution or stability of the MRI findings. CONCLUSION: The EnCor breast biopsy
      device has comparable results to those previously reported for other MRI-guided
      vacuum-assisted technologies.

PMID- 18821611
TI  - Hepatitis E: does it cause chronic hepatitis?
AB  - Hepatitis E virus (HEV) is considered an agent responsible for acute hepatitis
      that does not progress to chronic hepatitis. We identified 14 cases of acute HEV
      infection in three patients receiving liver transplants, nine receiving kidney
      transplants, and two receiving kidney and pancreas transplants. All patients were
      positive for serum HEV RNA. Chronic hepatitis developed in eight patients, as
      confirmed by persistently elevated aminotransferase levels, serum HEV RNA, and
      histologic features of chronic hepatitis. The time from transplantation to
      diagnosis was significantly shorter and the total counts of lymphocytes and of
      CD2, CD3, and CD4 T cells were significantly lower in patients in whom chronic
      disease developed.

PMID- 18821612
TI  - A fresh look at interferon-alpha signaling and treatment outcomes in chronic
      hepatitis C.
AB  - Hepatitis C virus (HCV) infection is a major cause of chronic liver disease
      worldwide. The current standard therapy for chronic hepatitis C (CHC) consists of
      a combination of pegylated IFN alpha (pegIFNalpha) and ribavirin. It achieves a
      sustained viral clearance in only 50-60% of patients. To learn more about
      molecular mechanisms underlying treatment failure, we investigated IFN-induced
      signaling in paired liver biopsies collected from CHC patients before and after
      administration of pegIFNalpha. In patients with a rapid virological response to
      treatment, pegIFNalpha induced a strong up-regulation of IFN-stimulated genes
      (ISGs). As shown previously, nonresponders had high expression levels of ISGs
      before therapy. Analysis of posttreatment biopsies of these patients revealed
      that pegIFNalpha did not induce expression of ISGs above the pretreatment levels.
      In accordance with ISG expression data, phosphorylation, DNA binding, and nuclear
      localization of STAT1 indicated that the IFN signaling pathway in nonresponsive
      patients is preactivated and refractory to further stimulation. Some features
      characteristic of nonresponders were more accentuated in patients infected with
      HCV genotypes 1 and 4 compared with genotypes 2 and 3, providing a possible
      explanation for the poor response of the former group to therapy. Taken together
      with previous findings, our data support the concept that activation of the
      endogenous IFN system in CHC not only is ineffective in clearing the infection
      but also may impede the response to therapy, most likely by inducing a refractory
      state of the IFN signaling pathway.

PMID- 18821613
TI  - High relapse rate seen at week 72 for patients treated with R1626 combination
      therapy.

PMID- 18821615
TI  - Re: Transient elastography is unreliable for detection of cirrhosis in patients
      with acute liver damage.

PMID- 18821616
TI  - Transvascular and interstitial transport in rat hepatocellular carcinomas:
      dynamic contrast-enhanced MRI assessment with low- and high-molecular weight
      agents.
AB  - PURPOSE: To assess which MRI-derived kinetic parameters reflect decreased
      transvascular and interstitial transport when low- and high-molecular-weight
      agents are used in rat hepatocellular carcinomas. MATERIALS AND METHODS: Dynamic
      MRI after injection of a low-molecular-weight contrast agent of 0.56 kDa (Gd
      DOTA, gadoterate) and two high-molecular-weight contrast agents of 6.47 kDa
      (P792, gadomelitol) and 52 kDa (P717, carboxymethyldextran Gd-DOTA) was performed
      in rats with chemically induced hepatocellular carcinomas. The data were analyzed
      with the Kety compartmental model, the extended Kety compartmental model in which
      it is assumed that the tissue voxels contain a vascular component, and the St
      Lawrence and Lee distributed-parameter model. RESULTS: The extravascular
      extracellular space accessible to the contrast agent v(e) and the extraction
      fraction E decreased with increasing molecular weight of the contrast agent. In
      contrast, the volume transfer constant Ktrans did not differ significantly when
      low- or high-molecular-weight agents were used. CONCLUSION: In this animal model
      the results suggest that the accessible extravascular extracellular space and the
      extraction fraction are more sensitive indicators of decreased transvascular and
      interstitial transport with high-molecular-weight agents than the volume transfer
      constant, which is a lumped representation of blood flow and permeability.

PMID- 18821617
TI  - Reproducible MRI measurement of adipose tissue volumes in genetic and dietary
      rodent obesity models.
AB  - PURPOSE: To develop ratio MRI [lipid/(lipid+water)] methods for assessing lipid
      depots and compare measurement variability with biological differences among lean
      controls (spontaneously hypertensive rats [SHRs]), dietary obese rats (SHR-DOs),
      and genetic/dietary obese rats (SHROBs). MATERIALS AND METHODS: Images with and
      without chemical shift-selective (CHESS) water suppression were processed using a
      semiautomatic method that accounts for relaxometry, chemical shift, receive coil
      sensitivity, and partial volume. RESULTS: Partial volume correction improved
      results by 10% to 15%. Over six operators, volume variation was reduced to 1.9 mL
      from 30.6 mL for single-image-analysis with intensity inhomogeneity. For three
      acquisitions on the same animal, volume reproducibility was <1%. SHROBs had six
      times more visceral and eight times more subcutaneous adipose tissue than SHRs.
      SHR-DOs had enlarged visceral depots (three times larger than those in SHRs).
      SHROBs had significantly more subcutaneous adipose tissue, indicating a strong
      genetic component to this fat depot. Liver ratios in SHR-DO and SHROB were higher
      than in SHR, indicating elevated fat content. Among SHROBs, evidence suggested a
      phenotype SHROB* having elevated liver ratios and visceral adipose tissue
      volumes. CONCLUSION: Effects of diet and genetics on obesity were significantly
      larger than variations due to image acquisition and analysis, indicating that
      these methods can be used to assess accumulation/depletion of lipid depots in
      animal models of obesity.

PMID- 18821618
TI  - Quantitative analysis of diffusion-weighted magnetic resonance imaging of the
      pancreas: usefulness in characterizing solid pancreatic masses.
AB  - PURPOSE: To evaluate whether measurement of apparent diffusion coefficient (ADC)
      and pure diffusion coefficient (D) can help to characterize solid pancreatic
      masses. MATERIALS AND METHODS: Diffusion-weighted MR imaging was performed in
      both a patient group (n = 71; pancreatic cancer [n = 47], mass-forming
      pancreatitis [n = 13], solid pseudopapillary neoplasm [n = 6], and neuroendocrine
      tumor [n = 5]) and a normal control group (n = 11) by applying three b-factors of
      0, 500, and 1000 sec/mm(2). ADC(500), ADC(1000), D (ADC using b = 500 and 1000
      sec/mm(2)), and perfusion fraction (f, 1- exp [-500 sec/mm(2) x (ADC(500) - D)])
      of normal pancreas, pancreatic cancer, and mass-forming pancreatitis were
      compared using the Kruskal-Wallis test. Receiver operating characteristic (ROC)
      analysis was performed to evaluate the diagnostic performance and optimal cutoff
      value of these parameters in differentiating pancreatic cancer from mass-forming
      pancreatitis. RESULTS: Normal pancreas had significantly higher mean ADC(500),
      ADC(1000), and f than either pancreatic cancer (P < 0.001, < 0.001, and 0.004,
      respectively) or mass-forming pancreatitis (P < 0.001, < 0.001, and 0.002,
      respectively). ADC(500), ADC(1000), and D of mass-forming pancreatitis were
      significantly lower than those of pancreatic cancer (P = 0.002, 0.004, and 0.014,
      respectively). Sensitivities and specificities in the diagnosis of pancreatic
      cancer were 72.3% and 76.9% for ADC(500), 87.2% and 69.2% for ADC(1000), 87.2%
      and 61.5% for D, and 42.6% and 92.3% for f, respectively. CONCLUSION: Measurement
      of ADC and D may be helpful in differentiating pancreatic cancers from mass
      forming pancreatitis.

PMID- 18821619
TI  - Magnetic resonance imaging and spectroscopy for monitoring liver steatosis.
AB  - PURPOSE: To compare noninvasive MRI and magnetic resonance spectroscopy (MRS)
      methods with liver biopsy to quantify liver fat content. MATERIALS AND METHODS:
      Quantification of liver fat was compared by liver biopsy, proton MRS, and MRI
      using in-phase/out-of-phase (IP/OP) and plus/minus fat saturation (+/-FS)
      techniques. The reproducibility of each MR measure was also determined. An
      additional group of overweight patients with steatosis underwent hepatic MRI and
      MRS before and after a six-month weight-loss program. RESULTS: A close
      correlation was demonstrated between histological assessment of steatosis and
      measurement of intrahepatocellular lipid (IHCL) by MRS (r(s) = 0.928, P < 0.0001)
      and MRI (IP/OP r(s) = 0.942, P < 0.0001; FS r(s) = 0.935, P < 0.0001). Following
      weight reduction, four of five patients with >5% weight loss had a decrease in
      IHCL of >or=50%. CONCLUSION: These findings suggest that standard MRI protocols
      provide a rapid, safe, and quantitative assessment of hepatic steatosis. This is
      important because MRS is not available on all clinical MRI systems. This will
      enable noninvasive monitoring of the effects of interventions such as weight loss
      or pharmacotherapy in patients with fatty liver diseases.

PMID- 18821620
TI  - Three-dimensional fast spoiled gradient-echo dual echo (3D-FSPGR-DE) with water
      reconstruction: preliminary experience with a novel pulse sequence for gadolinium
      enhanced abdominal MR imaging.
AB  - PURPOSE: To compare three-dimensional fast spoiled gradient-echo dual-echo (3D
      FSPGR-DE) with water reconstruction to conventional 3D-FSPGR for gadolinium
      enhanced abdominal imaging. MATERIALS AND METHODS: Sixty-five patients underwent
      abdominal MRI on a 1.5T GE-HDx MR scanner using gadolinium-enhanced 3D-FSPGR and
      3D-FSPGR-DE imaging. Qualitatively, FSPGR-DE and 3D-FSPGR images were reviewed
      side by side for normal anatomic structures, artifacts, and image quality. The
      images were reviewed separately for abnormalities of abdominal organs. Receiver
      operating characteristic (ROC) curve analysis was performed. Quantitative
      analysis measured mean signal intensity of liver, spleen, aorta, liver lesions,
      and noise. RESULTS: Observers preferred FSPGR-DE for evaluating liver, vessels,
      muscles, and subcutaneous tissues. Fat suppression was superior on FSPGR-DE in 63
      (0.97) and 61 (0.94) of 65 cases for two observers. FSPGR-DE showed less
      susceptibility artifact in 47 (0.72) and 41 (0.63) cases, better signal in edge
      slices in 60 (0.92) and 60 (0.92) cases, less phase artifact in 42 (0.65) and 45
      (0.69) cases, and less parallel imaging artifact in 13 (0.20) and 10 (0.15)
      cases. Images were equivalent for depicting abdominal findings with no difference
      in the area under the ROC curve. FSPGR-DE images showed a 20%, 29%, and 34%
      increase in liver, splenic, and aortic signal, respectively, and a 45% and 62%
      increase in liver-lesion contrast and contrast-to-noise ratio (CNR),
      respectively. CONCLUSION: Gadolinium-enhanced 3D-FSPGR-DE with water
      reconstruction provides volumetric abdominal imaging with superior image quality,
      more homogeneous fat suppression, reduced artifacts, and improved image signal
      and homogeneity.

PMID- 18821621
TI  - Nephrogenic systemic fibrosis: possible mechanisms and imaging management
      strategies.

PMID- 18821622
TI  - Steady-state free-precession (SSFP) cine MRI in distinguishing normal and
      bicuspid aortic valves.
AB  - PURPOSE: To assess the diagnostic sensitivity and specificity of double-oblique
      true fast imaging with steady-state precession (SSFP) cine MRI in distinguishing
      normal and bicuspid aortic valves. MATERIALS AND METHODS: Echocardiograms on
      patients referred for MRI of the heart and thoracic aorta over a four-year period
      were reviewed retrospectively. A total of 17 patients with bicuspid aortic valve
      were identified and compared to 21 randomly chosen control patients. All patients
      had double-oblique SSFP (True FISP) cine MRI of the aortic valve independently
      assessed by two radiologists in a blinded fashion, and graded as bicuspid or
      normal. Image quality was graded as 1, 2, or 3. Discordance was resolved by
      consensus. RESULTS: A total of 38 cases were reviewed (27 men, 11 women; age
      range = 15-67 years, mean = 25.33 years). Interobserver agreement was 0.97 (36/38
      cases). One case of normal tricuspid valve was reported as bicuspid by both
      readers (false-positive). All cases in which disparity arose were rated
      suboptimal by both readers (grade 2 or 3). Consensus review yielded sensitivity =
      100%, specificity = 95.2%, positive predictive value = 94.4%, and negative
      predictive value = 100%; overall diagnostic accuracy was 97.36%. Interobserver
      agreement was 0.97. CONCLUSION: Double-oblique True FISP cine MR imaging of the
      aortic valve is 100% sensitive and 95% specific in distinguishing normal and
      bicuspid aortic valves.

PMID- 18821623
TI  - Kidney transplantation: structural and functional evaluation using MR Nephro
      Urography.
AB  - End-stage-renal disease (ESRD) is a major health issue in the United States, and
      the Medicare costs of ESRD totaled nearly USD 21 billion in 2005. Renal
      transplantation has emerged as the treatment of choice in this patient
      population, providing improved quality of life and lower healthcare costs
      compared with other treatment options. Imaging evaluation of a graft kidney plays
      a critical role in the postoperative care of the renal transplant patient. In the
      past, diagnostic evaluation of the transplant kidney has depended upon a
      combination of ultrasonography, computed tomography, MRI, and biopsy, used in
      conjunction with the patient's clinical presentation. However, new and developing
      advances in MR technology has lead to the development of MR Nephro-Urography
      (MRNU), which provides both anatomic and functional evaluation of the kidney in a
      single examination. It is expected that the increasing use of MRNU will have a
      significant impact on the management of renal transplant patients. This review
      describes MRNU methodology, examines known posttransplant complications, and
      highlights the utility of MRNU as a comprehensive imaging examination to diagnose
      both surgical and medical complications of the transplant kidney.

PMID- 18821624
TI  - Traumatic extra-axial hemorrhage: correlation of postmortem MSCT, MRI, and
      forensic-pathological findings.
AB  - PURPOSE: To evaluate the diagnostic accuracy of in situ postmortem multislice
      computed tomography (MSCT) and magnetic resonance imaging (MRI) in the detection
      of primary traumatic extra-axial hemorrhage. MATERIALS AND METHODS: Thirty
      forensic neurotrauma cases and 10 nontraumatic controls who underwent both in
      situ postmortem cranial MSCT and MR imaging before autopsy were retrospectively
      reviewed. Both imaging modalities were analyzed in view of their accuracy,
      sensitivity, and specificity concerning the detection of extra-axial hemorrhage.
      Statistical significance was calculated using the McNemar test. kappa values for
      interobserver agreement were calculated for extra-axial hemorrhage types and to
      quantify the agreement between both modalities as well as MRI, CT, and forensics,
      respectively. RESULTS: Analysis of the detection of hemorrhagic localizations
      showed an accuracy, sensitivity, and specificity of 89%, 82%, and 92% using CT,
      and 90%, 83%, and 94% using MRI, respectively. MRI was more sensitive than CT in
      the detection of subarachnoid hemorrhagic localizations (P = 0.001), whereas no
      significant difference resulted from the detection of epidural and subdural
      hemorrhagic findings (P = 0.248 and P = 0.104, respectively). Interobserver
      agreement for all extra-axial hemorrhage types was substantial (CT kappa = 0.76;
      MRI kappa = 0.77). The agreement of both modalitites was almost perfect (readers
      1 and 2 kappa = 0.88). CONCLUSION: CT and MRI are of comparable potential as
      forensic diagnostic tools for traumatic extra-axial hemorrhage. Not only of
      forensic, but also of clinical interest is the observation that most thin blood
      layers escape the radiological evaluation.

PMID- 18821625
TI  - Identifying lesion growth with MR imaging in acute ischemic stroke.
AB  - PURPOSE: To determine whether different MR diffusion- and perfusion-weighted
      imaging (DWI and PWI) parameters are important in distinguishing lesion growth
      from the acute lesion and from oligemia. MATERIALS AND METHODS: MR DWI and PWI
      were acquired from thirteen patients. We defined three regions: (i) LESION -
      intersection of acute and final lesions, (ii) GROWTH - portion of final lesion
      not part of acute lesion, and (iii) OLIGEMIA - region of perfusion abnormality
      not part of either the acute or final lesions. We used logistic regression
      modeling to distinguish GROWTH from LESION and from OLIGEMIA on a voxel-wise
      basis using DWI- and PWI-based parameters. Final models were selected based on
      the Wald statistic and validated by cross-validation using the mean (+/- standard
      deviation) area under the curve (AUC) from receiver operating characteristic
      analysis. RESULTS: The final model for differentiating GROWTH from LESION
      included DWI, the apparent diffusion coefficient (ADC), cerebral blood flow (CBF)
      and tissue type (AUC = 0.939 +/- 0.028). The final model for differentiating
      GROWTH from OLIGEMIA included DWI, ADC, CBF, and time-to-peak (AUC = 0.793 +/-
      0.106). CONCLUSION: Different MR parameters are important in differentiating
      lesion growth from acute lesion and from oligemia in acute ischemic stroke.

PMID- 18821626
TI  - Maturational changes in diffusion anisotropy in the rat corpus callosum:
      comparison with quantitative histological evaluation.
AB  - PURPOSE: To determine the main histological components that affect fractional
      anisotropy (FA) in postnatal development of the rat corpus callosum and compare
      FA values with histological changes evaluated quantitatively. MATERIALS AND
      METHODS: Diffusion tensor image (DTI) data of the rat (postnatal 1-10 weeks)
      corpus callosum were obtained with a 7.0 T MR scanner. Histological parameters
      were quantitatively assessed in toluidine blue-stained semithin sections. Simple
      and multiple linear regression analyses were performed to investigate
      relationships between FA values and histological variables. RESULTS: The mean FA
      value (mFA) increased significantly in the early growth stages, whereas the
      change became smaller after postnatal week 4. Simple regression analysis showed a
      high correlation between the area of myelin sheath and mFA (r = 0.856; P < 0.01).
      The area of extracellular space correlated negatively with mFA (r = -0.813; P <
      0.01). In a forward stepwise analysis, the area of myelin sheath had the
      strongest influence on mFA (P < 0.001), followed by the number of unmyelinated
      axons (P = 0.113). Multiple linear regression analysis revealed that both
      parameters predicted mFA with a highly significant adjusted correlation
      coefficient (r(2) adj. = 0.738, P < 0.001). CONCLUSION: During the early
      development stage in the rat corpus callosum, the strongest contribution to FA
      value is the area of myelin sheath.

PMID- 18821627
TI  - Manganese-enhanced MRI of the rat visual pathway: acute neural toxicity, contrast
      enhancement, axon resolution, axonal transport, and clearance of Mn(2+).
AB  - PURPOSE: To provide dose-response data for the safe and effective use of MnCl(2)
      for manganese (Mn(2+)) -enhanced MRI (MEMRI) of the visual pathway. MATERIALS AND
      METHODS: Retinal ganglion cell (RGC) toxicity, CNR in MEMRI, axon density
      resolution for MEMRI, mode of axonal transport and clearance of Mn(2+) from the
      vitreous after ivit were investigated. After 0, 30, 150, 300, 1500, and 3000 nmol
      ivit MnCl(2), neural toxicity was measured by counting surviving RGC back-filled
      with FluroGold (FG), CNR of the vitreous body and visual pathway by three
      dimensional (3D) MEMRI, resolution of ON axon density by correlating CNR with
      axon density, and axonal transport of Mn(2+) by studying CNR in 3D MEMRI of the
      ON after ion of 200 nmol MnCl(2). RESULTS: There were no changes in RGC density
      after ivit MnCl(2) <or= 150 nmol, and reductions of 12%, 57%, and 94% occurred
      after 300, 1500, and 3000 nmol MnCl(2). CNR increased in the visual pathway with
      MnCl(2) <or= 300 nmol, and decreased when the dose was raised further. Minimum
      detectable ON axon densities were 125,000/mm(2). After 200 nmol ion MnCl(2),
      CNR>0 were recorded distally from the ion site, but there was no signal in the
      retina. At ivit doses >1500 nmol, clearance from the vitreous body was impaired.
      CONCLUSION: The optimal dose for MEMRI of the rat visual pathway was found to be
      150-300 nmol ivit MnCl(2). Higher doses are toxic, causing RGC death, impair
      active clearance from the vitreous, and loss of Mn(2+) enhancement throughout the
      visual pathway. Mn(2+) traffic within RGC axons is mediated mainly by anterograde
      transport.

PMID- 18821628
TI  - Multicenter trial: comparison of two different formulations and application
      systems of low-dose nasal midazolam for routine magnetic resonance imaging of
      claustrophobic patients.
AB  - PURPOSE: To prospectively assess and compare two formulations and methods of
      administration of low-dose nasal midazolam for the treatment of claustrophobic
      patients undergoing magnetic resonance imaging (MRI) as part of a multicenter
      Phase III trial. MATERIALS AND METHODS: In all, 108 consecutive adult
      claustrophobic patients were randomly assigned to one of two treatment groups
      (multidose group: MDG, unit-dose group: UDG). MDG encompassed 55 patients who
      received intranasally a 0.5% midazolam formulation into each nostril (total dose,
      1.0 mg), whereas the 53 patients in UDG received a 1% midazolam formulation into
      only one nostril (total dose, 1.0 mg). This initial dose could be repeated once.
      Patient tolerance and anxiety were assessed using a questionnaire and a visual
      analog scale immediately before and after MRI. Image quality was evaluated using
      a five-point scale. RESULTS: In all, 53/55 MR examinations (96%) with MDG and
      52/53 (98%) with UDG were completed successfully. The dose of 1 mg had to be
      repeated significantly less often in UDG compared to MDG (4/53, 8% vs. 13/55,
      24%; P = 0.003). The image quality of all MR examinations was rated good to
      excellent, and slightly better in UDG (P = 0.045). CONCLUSION: Nasally applied
      low-dose midazolam is a patient-friendly solution to facilitate MRI of
      claustrophobic patients. The nasal spray of UDG is superior to that of MDG with a
      necessity of additional dosing.

PMID- 18821629
TI  - In vitro investigation of pacemaker lead heating induced by magnetic resonance
      imaging: role of implant geometry.
AB  - PURPOSE: To evaluate the effect of the geometry of implantable pacemakers (PMs)
      on lead heating induced by magnetic resonance imaging (MRI). MATERIALS AND
      METHODS: In vitro experiments were conducted with two different setups, using
      fluoroptic probes to measure the temperature increase. The first experiment
      consisted of a rectangular box filled with a gelled saline and a pacemaker with
      its leads. This box was exposed in an MRI birdcage coil to a sinusoidal 64-MHz
      field with a calibrated whole-body specific absorption rate (WB-SAR) of 1 W/kg.
      The highest SAR and temperature increase (3000 W/kg, 12 degrees C) occurred for
      the implant configuration having the largest area. The second experimental setup
      consisted of a human-shaped torso filled with gelled saline. In this setup the PM
      and its lead were exposed to a real MRI scanner, using clinical sequences with WB
      SAR up to 2 W/kg. RESULTS: We found that higher heating occurs for configurations
      with longer exposed lead lengths and that right chest PMs showed the highest
      temperature and local SAR (11.9 degrees C, 2345 W/kg), whereas the left chest PMs
      were less heated (6.3 degrees C, 1362 W/kg). Implant geometry, exposed lead
      length, and lead area must be considered in the wide variation of temperature
      increases induced by MRI. CONCLUSIONS: The amount of MRI-induced lead tip heating
      depends strongly on implant geometry, particularly the lead area, exposed lead
      length, and position of the implant in the phantom. Critical lead tip heating was
      found for the longer leads. Therefore, to minimize MRI-induced lead tip heating,
      the PM lead should be as short as possible.

PMID- 18821630
TI  - Evaluation of motion correction effect and image quality with the periodically
      rotated overlapping parallel lines with enhanced reconstruction (PROPELLER)
      (BLADE) and parallel imaging acquisition technique in the upper abdomen.
AB  - PURPOSE: To evaluate motion correction effect and image quality in the upper
      abdomen with the periodically rotated overlapping parallel lines with enhanced
      reconstruction (PROPELLER) (BLADE) and parallel imaging acquisition technique.
      MATERIALS AND METHODS: A total of 50 consecutive patients underwent abdominal MR
      imaging. Fat-saturated T2-weighted turbo spin-echo sequences were obtained by
      respiratory triggering. The subjects were examined with three different
      conditions of echo train length (ETL), blade width, and percent k-space coverage
      in the same scanning time: 19/30/100%, 30/30/100%, and 30/52/175%, which were
      designated as L/C(1), L/C(2), and L/C(3), respectively. The parallel imaging
      acquisition technique was used to either reduce ETL from 30 to 19 in L/C(1) or
      increase k-space coverage from 100% to 175% in L/C(3) compared with L/C(2).
      Motion and streak artifacts, and overall image quality were evaluated visually by
      two radiologists, independently. RESULTS: Motion and streak artifacts were mostly
      reduced in L/C(3) condition. The L/C(3) image also gave the best overall image
      quality compared with other conditions (P < 0.001). The inter-rater reliability
      for each evaluation agreed well. CONCLUSION: In upper abdominal BLADE MRI, it was
      possible to reduce image artifacts and obtain better image quality by increasing
      the k-space coverage with parallel imaging in the same scanning time.

PMID- 18821631
TI  - Diffusion-weighted MR imaging for the evaluation of seminal vesicle invasion in
      prostate cancer: initial results.
AB  - PURPOSE: To evaluate the accuracy of T2-weighted (T2WI) with diffusion-weighted
      imaging (DWI) as compared with T2WI alone for predicting seminal vesicle invasion
      (SVI) of prostate cancer. MATERIALS AND METHODS: A total of 30 patients with SVI
      and 136 patients without SVI who underwent prostate MR imaging were included in
      the study. MR images were analyzed retrospectively and independently by two
      readers for SVI on T2WI and T2WI with DWI using a 5-point scale. RESULTS: For
      predicting SVI, the specificity for T2WI with DWI and for T2WI was 97% and 87%,
      respectively, and accuracy was 96% and 87%, respectively, as determined by the
      experienced reader (P < 0.01). For the less experienced reader, the specificity
      for T2WI with DWI and for T2WI was 96% and 81%, respectively, and accuracy was
      90% and 77%, respectively (P < 0.01). The diagnostic performance of the less
      experienced reader with T2WI with DWI led to significant improvement of the area
      under the receiver operating characteristic curve (Az) as compared with T2WI
      alone (Az = 0.815 versus 0.696; P < 0.01). Interreader agreement showed a
      substantial agreement (kappa = 0.613) for T2WI, and a substantial agreement
      (kappa = 0.737) for T2WI with DWI. CONCLUSION: For predicting SVI, T2WI with DWI
      showed a better diagnostic performance than T2WI alone. Additionally, the
      accuracy of the less experienced reader using T2WI with DWI showed a significant
      improvement as compared with T2WI alone.

PMID- 18821632
TI  - Investigation of protein binding affinity and preferred orientations in ion
      exchange systems using a homologous protein library.
AB  - A library of cold shock protein B (CspB) mutant variants was employed to study
      protein binding affinity and preferred orientations in cation exchange
      chromatography. Single site mutations introduced at charged amino acids on the
      protein surface resulted in a homologous protein set with varying charge density
      and distribution. The retention times of the mutants varied significantly during
      linear gradient chromatography. While the expected trends were observed with
      increasing or decreasing positive charge on the protein surface, the degree of
      change was a strong function of the location and microenvironment of the mutated
      amino acid. Quantitative structure-property relationship (QSPR) models were
      generated using a support vector regression technique that was able to give good
      predictions of the retention times of the various mutants. Molecular descriptors
      selected during model generation were used to elucidate the factors affecting
      protein retention. Electrostatic potential maps were also employed to provide
      insight into the effects of protein surface topography, charge density and charge
      distribution on protein binding affinity and possible preferred binding
      orientations. The use of this protein mutant library in concert with the
      qualitative and quantitative analyses presented in the article provides an
      improved understanding of protein behavior in ion exchange systems.

PMID- 18821633
TI  - Magnetization transfer contrast and T2 mapping in the evaluation of cartilage
      repair tissue with 3T MRI.
AB  - PURPOSE: To use magnetization transfer (MT) imaging in the visualization of
      healthy articular cartilage and cartilage repair tissue after different cartilage
      repair procedures, and to assess global as well as zonal values and compare the
      results to T2-relaxation. MATERIALS AND METHODS: Thirty-four patients (17 after
      microfracture [MFX] and 17 after matrix-associated autologous cartilage
      transplantation [MACT]) were examined with 3T MRI. The MT ratio (MTR) was
      calculated from measurements with and without MT contrast. T2-values were
      evaluated using a multiecho, spin-echo approach. Global (full thickness of
      cartilage) and zonal (deep and superficial aspect) region-of-interest assessment
      of cartilage repair tissue and normal-appearing cartilage was performed. RESULTS:
      In patients after MFX and MACT, the global MTR of cartilage repair tissue was
      significantly lower compared to healthy cartilage. In contrast, using T2,
      cartilage repair tissue showed significantly lower T2 values only after MFX,
      whereas after MACT, global T2 values were comparable to healthy cartilage. For
      zonal evaluation, MTR and T2 showed a significant stratification within healthy
      cartilage, and T2 additionally within cartilage repair tissue after MACT.
      CONCLUSION: MT imaging is capable and sensitive in the detection of differences
      between healthy cartilage and areas of cartilage repair and might be an
      additional tool in biochemical cartilage imaging. For both MTR and T2 mapping,
      zonal assessment is desirable.

PMID- 18821635
TI  - Application of magnetic force-based cell patterning for controlling cell-cell
      interactions in angiogenesis.
AB  - To investigate the effects of cell-cell interactions on cellular function, the
      microenvironment surrounding cells should be precisely controlled. Here, we
      describe a cell patterning technique, which utilizes magnetic force and magnetite
      nanoparticles. This method was used to develop cell culture arrays for
      investigation of cell behaviors in angiogenesis. Pin holder devices that contain
      more than 6,000 pillars on the surface are used for fabricating the cell culture
      arrays by setting it on a magnet. The magnetically labeled cells were arranged by
      magnetic distribution. When the human umbilical vein endothelial cells are
      arranged at 250 microm intervals (5.9 cells/spot), the cells spread toward other
      cell cluster on adjacent spots in 4.5 h, and formed cord-like structures in 8.5
      h. It was shown that cell-cell interactions were successfully investigated using
      magnetic cell arrangement.

PMID- 18821634
TI  - Signal features of the atherosclerotic plaque at 3.0 Tesla versus 1.5 Tesla:
      impact on automatic classification.
AB  - PURPOSE: To investigate the impact of different field strengths on determining
      plaque composition with an automatic classifier. MATERIALS AND METHODS: We
      applied a previously developed automatic classifier-the morphology enhanced
      probabilistic plaque segmentation (MEPPS) algorithm-to images from 20 subjects
      scanned at both 1.5 Tesla (T) and 3T. Average areas per slice of lipid-rich core,
      intraplaque hemorrhage, calcification, and fibrous tissue were recorded for each
      subject and field strength. RESULTS: All measurements showed close agreement at
      the two field strengths, with correlation coefficients of 0.91, 0.93, 0.95, and
      0.93, respectively. None of these measurements showed a statistically significant
      difference between field strengths in the average area per slice by a paired t
      test, although calcification tended to be measured larger at 3T (P = 0.09).
      CONCLUSION: Automated classification results using an identical algorithm at 1.5T
      and 3T produced highly similar results, suggesting that with this acquisition
      protocol, 3T signal characteristics of the atherosclerotic plaque are
      sufficiently similar to 1.5T characteristics for MEPPS to provide equivalent
      performance.

PMID- 18821636
TI  - Biocatalytic polyester acrylation--process optimization and enzyme stability.
AB  - An OH-functional polyester has been acrylated via transesterification of ethyl
      acrylate, catalyzed by Candida antarctica lipase B (CalB) in two different
      preparations: Novozym 435 and immobilized on Accurel MP1000. The batch process
      resulted in incomplete acrylation as well as severe degradation of the polyester.
      A high degree of acrylation was achieved by optimization through the application
      of low pressure (15 kPa), continuous inflow of ethyl acrylate and continuous
      distillation to evaporate the by-product, ethanol. The enzyme preparations
      displayed good stability with half-lives of 180 and 324 h for Novozym 435 and
      CalB/MP1000, respectively. This translates into product yields of 3600 and 6200
      times the weight of the catalyst, indicating that the enzyme will have a marginal
      impact on the total process cost.

PMID- 18821637
TI  - An efficient and scalable process for helper-dependent adenoviral vector
      production using polyethylenimine-adenofection.
AB  - Safety requirements for adenoviral gene therapy protocols have led to the
      development of the third generation of vectors commonly called helper-dependent
      adenoviral vectors (HDVs). HDVs have demonstrated a high therapeutic potential;
      however, the poor efficiency and reliability of the actual production process
      hampers further large-scale clinical evaluation of this new vector. The current
      HDV production methods involve a preliminary rescue step through transfection of
      adherent cell cultures by an HDV plasmid followed by a helper adenovirus (HV)
      infection. Amplification by serial co-infection of complementary cells allows an
      increase in the HDV titer. Using a HEK293 FLP/frt cell system in suspension
      culture, an alternative protocol to the current transfection/infection procedure
      was evaluated. In this work, the adenofection uses the HDV plasmid linked to the
      HV with the help of polyethylenimine (PEI) and has shown to outperform standard
      protocols by producing higher HDV yield. The influence of complex composition on
      the HDV production was examined by a statistical design. The optimized
      adenofection and amplification conditions were successively performed to generate
      HDV at the 3 L bioreactor scale. Following only two serial co-infection passages,
      up to 1.44 x 10(8) HDV infectious units/mL of culture were generated, which
      corresponded to 26% of the total particles produced. This production strategy,
      realized in cell suspension culture, reduced process duration and therefore the
      probability of vector recombination by introducing a cost-effective transfection
      protocol, ensuring production of high-quality vector stock.

PMID- 18821638
TI  - Are behavioral interventions for arthritis effective with minorities? Addressing
      racial and ethnic diversity in disability and rehabilitation.
AB  - OBJECTIVE: To determine whether research evaluating the effectiveness of
      behavioral interventions for arthritis demonstrates that these interventions are
      effective with, and appropriately utilized by, minority participants. METHODS: A
      systematic review was conducted of arthritis intervention research from 1997 to
      2008. For each article, information was gathered on the percentage of
      participants who were from different racial/ethnic groups, whether interventions
      were shown to be effective for minority participants, whether differential
      attrition analyses were conducted, whether efforts were reported in minority
      recruitment and retention, and whether attempts were made to make interventions
      culturally appropriate. RESULTS: We identified 25 randomized intervention
      studies. Of these, only 2 reported on whether the intervention was similarly
      effective for white and black patients (equal effectiveness was found), and 6
      studies reported examining differences in attrition by race (higher attrition in
      nonwhites was found in 1 study). Most studies did not report the percentage of
      participants from specific minority groups, and in many studies the percentage of
      minority participants was small. No studies reported making systematic efforts to
      assure that interventions were culturally appropriate for minority participants.
      CONCLUSION: Minority patients with arthritis are at risk for higher levels of
      disability than white patients, but little is known about whether evidence-based
      interventions for arthritis are effective for culturally diverse patients. In
      addition, minority patients appear to be underrepresented in intervention
      research, and too little attention has been paid to minority recruitment and
      assuring that interventions are culturally appropriate for diverse patients.

PMID- 18821640
TI  - Family factors, emotional functioning, and functional impairment in juvenile
      fibromyalgia syndrome.
AB  - OBJECTIVE: Family factors and emotional functioning can play an important role in
      the ability of adolescents with juvenile primary fibromyalgia syndrome (JPFS) to
      cope with their condition and function in their everyday lives. The primary
      objectives of this study were to determine 1) whether adolescents with JPFS and
      their caregivers differed from healthy age-matched comparison peers and their
      caregivers in terms of emotional distress and functional impairment; 2) whether
      there were any differences in the family environment of adolescents with JPFS
      compared with healthy comparison peers; and 3) which individual-, caregiver-, and
      family-level variables were associated with functional impairment in adolescents
      with JPFS. METHODS: Participants were 47 adolescents with JPFS recruited from a
      pediatric rheumatology clinic and 46 comparison peers without chronic illness
      matched for age, sex, and race. Participants and their caregivers (all mothers)
      completed a battery of standardized measures administered in their homes.
      RESULTS: Adolescents with JPFS had greater internalizing and externalizing
      symptoms than healthy comparison peers. Mothers of adolescents with JPFS reported
      twice as many pain conditions and significantly greater depressive symptoms than
      mothers of comparison peers. The JPFS group also had poorer overall family
      functioning and more conflicted family relationships. In adolescents with JPFS,
      maternal pain history was associated with significantly higher functional
      impairment. CONCLUSION: Increased distress and chronic pain are evident in
      families of adolescents with JPFS, and family relationships are also impacted.
      Implications for child functional impairment and the need for inclusion of
      caregivers in treatment are discussed.

PMID- 18821641
TI  - Association of body composition with disability in rheumatoid arthritis: impact
      of appendicular fat and lean tissue mass.
AB  - OBJECTIVE: To explore the association of measures of body composition with
      disability in patients with rheumatoid arthritis (RA). METHODS: Patients with RA
      underwent total body dual-energy x-ray absorptiometry for measurement of total
      and regional body fat and lean mass. The associations of measures of fat and lean
      mass with disability, measured with the Health Assessment Questionnaire (HAQ),
      were explored for the total cohort and by sex, controlling for pertinent
      demographic, lifestyle, and RA disease and treatment covariates. RESULTS: We
      studied 197 subjects (118 women, 79 men). Median (interquartile range) HAQ score
      was 0.625 (0.125-1.25) and was significantly higher, indicating worse physical
      function, in women than in men. HAQ score was strongly correlated with
      depression, pain, RA duration, duration of morning stiffness, Disease Activity
      Score in 28 joints, radiographic damage scores, levels of physical and sedentary
      activities, and body composition, with increasing fat and decreasing lean mass
      associated with higher HAQ scores. Appendicular fat and lean mass demonstrated
      the strongest association per kilogram with HAQ. Mean HAQ score was 0.52 units
      higher for subjects in the highest versus the lowest quartile of appendicular fat
      mass (P<0.001), and 0.81 units higher for subjects in the lowest versus the
      highest quartile of appendicular lean mass (P<0.001). Adjusting for demographic
      and RA characteristics partially attenuated these associations. The joint
      associations of appendicular fat and lean mass on HAQ were additive without
      significant interaction. CONCLUSION: Body composition, particularly the amount of
      fat and lean mass located in the arms and legs, is strongly associated with
      disability in RA patients.

PMID- 18821642
TI  - Subclinical disability in valued life activities among individuals with
      rheumatoid arthritis.
AB  - OBJECTIVE: Subclinical disability, the need for modifications in task performance
      or frequency without reported difficulty with the task, has been identified as a
      stage along the disability continuum. We estimated the prevalence of subclinical
      disability in valued life activities (VLAs) among individuals with rheumatoid
      arthritis (RA), identified characteristics of individuals with VLA subclinical
      disability, and estimated the ability of VLA subclinical disability to predict
      later decrements in functioning. METHODS: Data were from 3 years of a
      longitudinal panel study of individuals with RA, for which annual structured
      telephone interviews are conducted (n=508 in year 1, n=442 in year 3).
      Respondents rated difficulty in VLAs and then reported whether they used any of 4
      behavioral modifications (limitations, extra time, help, or equipment) for each.
      Subclinical disability was defined for each VLA as no reported difficulty with
      use of any modification. Multiple regression analyses identified predictors of
      subclinical disability in year 1 and the role of year 1 subclinical disability in
      development of overt disability between year 1 and year 3. RESULTS: Almost three
      quarters of the subjects exhibited subclinical disability in at least 1 VLA in
      year 1. Duration of RA was consistently associated with subclinical disability.
      Individuals with subclinical disability at baseline were significantly more
      likely to experience increases in functional limitations (odds ratio [OR] 1.09,
      95% confidence interval [95% CI] 1.01-1.18) and VLA disability (OR 1.14, 95% CI
      1.06-1.23) over a prospective 2-year period. CONCLUSION: Subclinical disability
      may be a valuable marker of individuals in a disability transition phase who are
      particularly susceptible to intervention that would enable them to maintain
      functioning.

PMID- 18821643
TI  - Living with a fluctuating illness of ankylosing spondylitis: a qualitative study.
AB  - OBJECTIVE: To examine the relationship between illness fluctuations and how
      people with ankylosing spondylitis (AS) adapt to everyday life situations.
      METHODS: Twelve respondents, 8 women and 4 men, age 30-59 years with an AS
      duration of 6 months to 40 years participated in qualitative interviews. They
      were asked to give examples of how they lived their everyday life during good and
      bad times of illness. The text analyses consisted of familiarization with the
      content, identifying and coding meaningful statements, sorting them into
      categories, and condensing themes. RESULTS: Three different types of situations
      for those living with AS emerged from the analysis: ordinary life, slowed-down
      life, and disrupted life. Ordinary life included managing symptoms by
      incorporating motion into everyday life routines and adjusting tasks in work
      situations, sports activities, home life, and social activities. During slowed
      down life, an acute or insidious onset of stiffness and fatigue occurred that
      could be reversed by slowing down ordinary life for a period of time. During
      disrupted life, the respondents were unable to cope with everyday life because of
      inexplicable and unmanageable intense, localized, or distributed pain.
      CONCLUSION: By examining the relationships between illness and what people do to
      recover, 3 different life conditions were found: ordinary life, slowed-down life,
      and disrupted life. Living with AS requires a continuous but varying process of
      normalization of symptoms and everyday life within the framework of these 3
      illness conditions.

PMID- 18821644
TI  - Rheumatology gone global.

PMID- 18821645
TI  - Arthritis disability and heart disease disability.
AB  - OBJECTIVE: Arthritis is the most common health condition in midlife and late
      life, and heart disease is the leading cause of death. This article compares
      disability impacts of these 2 preeminent health problems. METHODS: Using data
      from the National Health Interview Survey Disability Supplement, we studied
      specific limitations and disabilities, accommodations used (buffers), and
      accommodations needed (barriers) for US population groups of adults with
      arthritis disability, heart disease disability, both arthritis and heart disease
      disability, and disability due to other conditions. Weights and complex SE
      adjusted for sample design. We hypothesized that arthritis disability is more
      extensive and troublesome than heart disease disability. RESULTS: People with
      arthritis disability had more numerous, longer, and more bothersome disabilities
      than people with heart disease disability. People with arthritis disability used
      more equipment and rehabilitation, whereas people with heart disease disability
      emphasized personal assistance, medications, and medical services. People with
      arthritis disability experienced more barriers and needs in activities and
      services. People with disabilities from both arthritis and heart disease were
      especially disadvantaged, with high levels of limitations and accommodations.
      People with disability from other conditions had the highest social
      participation, fewest disabilities, and most tailored accommodations of all
      groups. CONCLUSION: Arthritis had higher and more extensive disability impact
      than heart disease. Both groups had more difficulty, buffers, and barriers in
      their lives than people disabled by other conditions. Therefore, arthritis and
      heart disease are premier conditions for disability attention and alleviation in
      the US population.

PMID- 18821646
TI  - Effects of activity strategy training on pain and physical activity in older
      adults with knee or hip osteoarthritis: a pilot study.
AB  - OBJECTIVE: To examine effects of activity strategy training (AST), a structured
      rehabilitation program taught by occupational therapists and designed to teach
      adaptive strategies for symptom control and engagement in physical activity (PA).
      METHODS: A randomized controlled pilot trial was conducted at 4 sites (3 senior
      housing facilities and 1 senior center) in southeastern, lower Michigan. Fifty
      four older adults with hip or knee osteoarthritis (mean +/- SD age 75.3+/-7.1
      years) participated. At each site, older adults were randomly assigned to 1 of 2
      programs: exercise plus AST (Ex + AST) or exercise plus health education (Ex +
      Ed). The programs involved 8 sessions over 4 weeks with 2 followup sessions over
      a 6-month period, and were conducted concurrently within each site. Pain, total
      PA and PA intensity (measured objectively by actigraphy and subjectively by the
      Community Healthy Activities Model Program for Seniors questionnaire), arthritis
      self-efficacy, and physical function were assessed at baseline and posttest.
      RESULTS: At posttest, participants who received Ex + AST had significantly higher
      levels of objective peak PA (P=0.02) compared with participants who received Ex +
      Ed. Although not statistically significant, participants in Ex + AST tended to
      have larger pain decreases, increased total objective and subjective PA, and
      increased physical function. No effects were found for arthritis self-efficacy.
      CONCLUSION: Although participants were involved in identical exercise programs,
      participants who received AST tended to have larger increases in PA at posttest
      compared with participants who received health education. Future studies will be
      needed to examine larger samples and long-term effects of AST.

PMID- 18821647
TI  - Strength training for treatment of osteoarthritis of the knee: a systematic
      review.
AB  - OBJECTIVE: To assess the effectiveness of isolated resistance training on
      arthritis symptoms, physical performance, and psychological function in people
      with knee osteoarthritis. METHODS: A comprehensive systematic database search for
      randomized controlled trials was performed. Two reviewers independently assessed
      studies for potential inclusion. Study quality indicators, arthritis symptoms,
      muscle strength, functional performance, and psychological outcomes were
      extracted. The relative effect sizes (ES) were calculated with 95% confidence
      intervals. RESULTS: Eighteen studies enrolling 2,832 subjects were reviewed; the
      mean cohort age range was 55-74 years. In general, the quality of the reviewed
      literature was moderately robust; on average, 8 out of 12 quality criteria were
      accounted for in the reviewed literature. Self-reported measures of pain,
      physical function, and performance, along with muscle strength (mean 17.4%),
      maximal gait speed and chair stand time, and balance improved significantly
      following resistance training in 56-100% of studies where they were measured.
      Limitations included lack of data available for ES calculations and lack of
      adverse event and compliance reporting, particularly with regard to the actual
      training intensity versus the prescribed training intensity. CONCLUSION:
      Resistance training improved muscle strength and self-reported measures of pain
      and physical function in over 50-75% of this cohort; 50-100% of the studies
      reported a significant improvement in all but 1 performance-based physical
      function measure (walk time). The effects of resistance training on health
      related quality of life and depression are yet to be confirmed. More research
      needs to be conducted to establish dose-response relationships and the effect of
      resistance training on long-term disability, disease pathology, and progression.

PMID- 18821648
TI  - Reporting disease activity in clinical trials of patients with rheumatoid
      arthritis: EULAR/ACR collaborative recommendations.
AB  - OBJECTIVE: To make recommendations on how to report disease activity in clinical
      trials of rheumatoid arthritis (RA) endorsed by the European League Against
      Rheumatism (EULAR) and the American College of Rheumatology (ACR). METHODS: The
      project followed the EULAR standardized operating procedures, which use a three
      step approach: 1) expert-based definition of relevant research questions
      (November 2006); 2) systematic literature search (November 2006 to May 2007); and
      3) expert consensus on recommendations based on the literature search results
      (May 2007). In addition, since this is the first joint EULAR/ACR publication on
      recommendations, an extra step included a meeting with an ACR panel to approve
      the recommendations elaborated by the expert group (August 2007). RESULTS: Eleven
      relevant questions were identified for the literature search. Based on the
      evidence from the literature, the expert panel recommended that each trial should
      report the following items: 1) disease activity response and disease activity
      states; 2) appropriate descriptive statistics of the baseline, the endpoints and
      change of the single variables included in the core set; 3) baseline disease
      activity levels (in general); 4) the percentage of patients achieving a low
      disease activity state and remission; 5) time to onset of the primary outcome; 6)
      sustainability of the primary outcome; 7) fatigue. CONCLUSION: These
      recommendations endorsed by EULAR and ACR will help harmonize the presentations
      of results from clinical trials. Adherence to these recommendations will provide
      the readership of clinical trials with more details of important outcomes, while
      the higher level of homogeneity may facilitate the comparison of outcomes across
      different trials and pooling of trial results, such as in meta-analyses.

PMID- 18821649
TI  - The Ergonomic Assessment Tool for Arthritis: development and pilot testing.
AB  - OBJECTIVE: Ergonomic assessment and recommendations may help people with
      arthritis maintain employment; however, most ergonomic tools are designed to
      assess injury risk in the general population and are not specific to the needs of
      people with inflammatory arthritis (IA). Our objectives were to design and pilot
      test an ergonomic assessment tool for people with IA and to propose ergonomic
      modifications to prevent work loss and maintain at-work productivity. METHODS:
      Relevant content was identified in a literature review by an interdisciplinary
      team. Respecting some clients' reluctance to disclose arthritis to employers, no
      work site visit was required. An initial assessment tool was reviewed by a 4
      person expert panel, revised and pretested with 13 adults with IA by 3
      occupational therapists (OTs). The final tool, comprised of a self-assessment, an
      interview guide, and a solutions summary, was used in a pilot test of a
      multifaceted program designed to prevent work loss and maintain at-work
      productivity. One OT conducted all ergonomic consultations and followed up with
      phone calls at 1 month. Implementation of recommendations was evaluated at 3, 6,
      and 12 months. RESULTS: Nineteen women (mean age 51 years) with IA (mean disease
      duration 12 years) completed ergonomic assessments. A range of risks were
      identified and 87 recommendations were made (mean 4.5 per participant). At 1
      year, 85% of recommendations had been implemented by 74% of the participants.
      CONCLUSION: The Ergonomic Assessment Tool for Arthritis is a feasible and
      comprehensive process for identifying ergonomic job accommodations.

PMID- 18821650
TI  - Activity limitations and compensatory mechanism use following limited wrist
      fusion.
AB  - OBJECTIVE: To document the activity limitations experienced by patients who had
      undergone a 4-corner wrist fusion, and the compensatory mechanisms they use in
      daily life. METHODS: Patients completed 2 copies of the Adelaide Questionnaire, a
      measure with a standardized section and an individualized section. The test
      retest reliability of the questionnaire was evaluated. RESULTS: Twenty-five
      patients were recruited to the study, and 21 completed both questionnaires.
      Excellent test-retest reliability was gained for both the standardized and
      individualized sections of the Adelaide Questionnaire. CONCLUSION: Patients with
      4-corner wrist fusions report activity limitations following surgery,
      particularly with daily tasks that involve hand/forearm rotation and grip
      strength. Various compensatory mechanisms are used by the majority of patients.
      The impact of these mechanisms on activity limitations varies between patients,
      but often decreases impact of the activity limitations on everyday life.

PMID- 18821651
TI  - Compliance with biologic therapies for rheumatoid arthritis: do patient out-of
      pocket payments matter?
AB  - OBJECTIVE: To assess the impact of patient out-of-pocket (OOP) expenditures on
      adherence and persistence with biologics in patients with rheumatoid arthritis
      (RA). METHODS: An inception cohort of RA patients with pharmacy claims for
      etanercept or adalimumab during 2002-2004 was selected from an insurance claims
      database of self-insured employer health plans (n=2,285) in the US. Adherence was
      defined as medication possession ratio (MPR): the proportion of the 365 followup
      days covered by days supply. Persistence was determined using a survival analysis
      of therapy discontinuation during followup. Patient OOP cost was measured as the
      patient's coinsurance and copayments per week of therapy, and as the proportion
      of the total medication charges paid by the patient. Multivariate linear
      regression models of MPR and proportional hazards models of persistence were used
      to estimate the impact of cost, adjusting for insurance type and demographic and
      clinical variables. RESULTS: Mean +/- SD OOP expenditures averaged $7.84+/-$14.15
      per week. Most patients (92%) paid less than $20 OOP for therapy/week. The mean
      +/- SD MPR was 0.52+/-0.31. Adherence significantly decreased with increased
      weekly OOP (coeff= -0.0035, P<0.0001) and with a higher proportion of therapy
      costs paid by patients (coeff= -0.8794, P<0.0001), translating into approximately
      1 week of therapy lost per $5.50 increase in weekly OOP. Patients whose weekly
      cost exceeded $50 were more likely to discontinue than patients with lower costs
      (hazard ratio 1.58, P<0.001). CONCLUSION: Most patients pay less than $20/week
      for biologics, but a small number have high OOP expenses, associated with lower
      medication compliance. The adverse impact of high OOP costs on adherence,
      persistence, and outcomes must be considered when making decisions about
      increasing copayments.

PMID- 18821652
TI  - A 20-year-old man with right leg pain following orofacial surgery.

PMID- 18821655
TI  - Physical activity in adolescents with juvenile idiopathic arthritis.
AB  - OBJECTIVE: To explore physical activity (PA) in adolescents with juvenile
      idiopathic arthritis (JIA) compared with a healthy population and to examine
      associations between PA and disease-related factors. METHODS: Total energy
      expenditure (TEE), activity-related energy expenditure (AEE), PA level, and PA
      pattern were assessed with a 3-day activity diary. Aerobic capacity was assessed
      using a Symptom Limited Bicycle Ergometry test. Functional ability was assessed
      with the Childhood Health Assessment Questionnaire. Disease activity was assessed
      using Paediatric Rheumatology International Trials Organisation core set
      criteria. Overall well-being was measured using a visual analog scale, and time
      since diagnosis was assessed by retrospective study from patients' charts. We
      used a cross-sectional study design. Reference data were collected from healthy
      Dutch secondary school children. RESULTS: Thirty patients and 106 controls were
      included (mean+/-SD age 17.0+/-0.6 and 16.7+/-0.9 years, respectively). TEE, AEE,
      and PA level were significantly lower in the JIA group. The JIA group spent more
      time in bed and less time on moderate to vigorous PA. Only 23% of the JIA
      patients met public health recommendations to perform >or=1 hour daily moderate
      to vigorous PA compared with 66% in the reference group. Higher PA was associated
      with higher levels of well-being and maximal oxygen consumption. CONCLUSION:
      Adolescents with JIA have low PA levels and are at risk of losing the benefits of
      PA. Low PA is not related to disease activity, and control over the disease does
      not restore previous PA levels. Interventions by pediatric rheumatologists are
      needed to increase PA levels in patients with JIA.

PMID- 18821656
TI  - Feasibility and effectiveness of an aerobic exercise program in children with
      fibromyalgia: results of a randomized controlled pilot trial.
AB  - OBJECTIVE: To determine the feasibility of conducting a randomized controlled
      trial of a 12-week exercise intervention in children with fibromyalgia (FM) and
      to explore the effectiveness of aerobic exercise on physical fitness, function,
      pain, FM symptoms, and quality of life (QOL). METHODS: FM patients ages 8-18
      years were randomized to a 12-week exercise intervention of either aerobics or
      qigong. Both groups participated in 3 weekly training sessions. Program adherence
      and safety were monitored at each session. Data were collected at 3 testing
      sessions, 2 prior to and 1 after the intervention, and included FM symptoms,
      function, pain, QOL, and fitness measures. RESULTS: Thirty patients participated
      in the trial. Twenty-four patients completed the program; 4 patients dropped out
      prior to training and 2 dropped out of the aerobics program. Better adherence was
      reported in the aerobics group than in the qigong group (67% versus 61%).
      Significant improvements in physical function, functional capacity, QOL, and
      fatigue were observed in the aerobics group. Anaerobic function, tender point
      count, pain, and symptom severity improved similarly in both groups. CONCLUSION:
      It is feasible to conduct an exercise intervention trial in children with FM.
      Children with FM tolerate moderate-intensity exercise without exacerbation of
      their disease. Significant improvements in physical function, FM symptoms, QOL,
      and pain were demonstrated in both exercise groups; the aerobics group performed
      better in several measures compared with the qigong group. Future studies may
      need larger sample sizes to confirm clinical improvement and to detect
      differences in fitness in childhood FM.

PMID- 18821657
TI  - Impact of nervous system hyperalgesia on pain, disability, and quality of life in
      patients with knee osteoarthritis: a controlled analysis.
AB  - OBJECTIVE: Refractory, disabling pain associated with knee osteoarthritis (OA) is
      usually treated with total knee replacement. However, pain in these patients
      might be associated with central nervous sensitization rather than peripheral
      inflammation and injury. We evaluated the presence of hyperalgesia in patients
      scheduled for a total knee replacement due to knee osteoarthritis with refractory
      pain, and we assessed the impact of pressure pain threshold measurements (PPT) on
      pain, disability, and quality of life of these patients. METHODS: Sixty-two
      female patients were compared with 22 age-matched healthy controls without
      reported pain for the last year. PPT was measured at the lower extremities
      subcutaneous dermatomes, over the vastus medialis, adductor longus, rectus
      femoris, vastus lateralis, tibialis anterior, peroneus longus, iliacus, quadratus
      lumborum and popliteus muscles and at the supraspinous ligaments from L1-L5, over
      the L5-S1 and S1-S2 sacral areas and at the pes anserinus bursae and patellar
      tendon. RESULTS: Patients with knee OA had significantly lower PPT over all
      evaluated structures versus healthy control subjects (P<0.001). Lower PPT values
      were correlated with higher pain intensity, higher disability scores, and with
      poorer quality of life, except for the role-emotional and general health status.
      Combined PPT values over the patellar tendon, at the S2 subcutaneous dermatome
      and at the adductor longus muscle were the best predictors for visual analog
      scale and Western Ontario and McMaster Universities Osteoarthritis Index pain
      scores. CONCLUSION: Patients with pain due to osteoarthritis who were scheduled
      for total knee replacement showed hyperalgesia of nervous system origin that
      negatively impacted pain, knee functional capacity, and most aspects of quality
      of life.

PMID- 18821658
TI  - Effect of the early use of the anti-tumor necrosis factor adalimumab on the
      prevention of job loss in patients with early rheumatoid arthritis.
AB  - OBJECTIVE: To compare work disability and job loss in early rheumatoid arthritis
      (RA) patients receiving adalimumab plus methotrexate (adalimumab + MTX) versus
      MTX alone. METHODS: In this multicenter, randomized, controlled trial, patients
      with RA for <2 years who had never taken MTX and who self-reported work
      impairment were randomized to adalimumab + MTX or placebo + MTX for 56 weeks.
      Primary outcome was job loss of any cause and/or imminent job loss at or after
      week 16. Secondary outcomes included disease activity, function (Health
      Assessment Questionnaire [HAQ] score), and RA quality of life (RAQoL)
      questionnaire score. Work was evaluated with work diaries and the RA Work
      Instability Scale. RESULTS: Although job loss during the 56-week study was
      significantly lower with adalimumab + MTX (14 of 75 patients) compared with MTX
      alone (29 of 73 patients; P=0.005), the primary end point was not met (12 of 75
      versus 20 of 73 patients; P=0.092), likely owing to early drop out in the MTX
      group. There were significant improvements in American College of Rheumatology
      20% response criteria, 28-joint Disease Activity Score, DeltaHAQ, DeltaRAQoL, and
      working time lost in the adalimumab + MTX group. Twenty-four serious adverse
      events were reported in 17 participants, with no differences between groups.
      CONCLUSION: Adalimumab + MTX reduced job loss and improved productivity in early
      RA when compared with MTX alone, which supports the early use of anti-tumor
      necrosis factor therapy and suggests its cost efficacy.

PMID- 18821659
TI  - Diagnosis of remitting seronegative symmetrical synovitis with pitting edema in a
      patient with sarcoidosis: comment on the article by Dejaco et al.

PMID- 18821661
TI  - Educational and occupational outcomes among young adults with juvenile idiopathic
      arthritis.
AB  - OBJECTIVE: To examine educational and occupational outcomes among young adults
      with juvenile idiopathic arthritis (JIA) and peers during the transition from
      adolescence to emerging adulthood. METHODS: Families were recruited when children
      with JIA were 8-14 years old. At that time, each child with JIA was matched to a
      classmate of similar age, sex, and race for inclusion in a comparison group. For
      the current followup (12.64 years postdiagnosis), 45 participants with JIA, 46
      peers, and their parents completed questionnaires soon after the young person's
      18th birthday. Disease type and severity were rated by health care providers.
      RESULTS: Young adults with JIA and peers were similar on a variety of factors,
      including family background, scholastic and occupational self-concept, and
      academic competence. The proportion of participants who graduated from high
      school, were working, and expressed plans to attend postsecondary education or
      seek employment was similar between groups. Disease type, initial severity, and
      time since diagnosis were generally not associated with indices of educational
      and occupational attainment. CONCLUSION: Despite the challenge of having a
      chronic illness, young adults with JIA were similar to peers on numerous
      educational and occupational outcomes during the transition from adolescence to
      emerging adulthood. Interventions to assist academic or occupational functioning
      may not be necessary for all children with JIA, but additional research is needed
      to identify subgroups at risk for long-term difficulties.

PMID- 18821662
TI  - Hand function and performance of daily activities in systemic lupus
      erythematosus.
AB  - OBJECTIVE: To investigate hand problems in patients with systemic lupus
      erythematosus (SLE) and to explore consequences on the ability to perform daily
      activities. METHODS: One hundred nine patients with SLE completed a questionnaire
      assessing hand problems in terms of deficits in body structures, e.g., joints,
      and body functions including pain, grip force, and other physiologic functions of
      the hand, the Health Assessment Questionnaire (HAQ), and the Simple hand test.
      Patients who stated problems in hand function answered questions about
      performance of daily activities and to what extent different deficits in body
      structures and body functions interfered. RESULTS: Seventy-three percent of
      patients experienced hand problems and 42% reported interference with performance
      of daily activities. Problems from body structures of the hand were distributed
      relatively evenly over joints and tendons/muscles. Reduced grip force and
      activity-induced pain were the most commonly reported problems in body functions.
      The most affected activity area was productivity, namely household tasks, work at
      home, work/study, and child care; least affected was self-care. Reduced grip
      force followed by fumbling and pain were the most frequently reported body
      functions to create difficulties in performing daily activities. When comparing
      patients with and without difficulties in performing daily activities, there were
      significant differences in problems from tendons/muscles, joints in the thumb,
      reduced force, stiffness, fumbling, numbness/tingling, and the HAQ. CONCLUSION: A
      majority of the study group had hand problems and almost half of the group
      experienced difficulties in performing daily activities due to SLE. The most
      affected activity area was productivity, where reduced grip force, fumbling, and
      pain were the most interfering body functions.

PMID- 18821663
TI  - Work and sick leave among patients with early inflammatory joint conditions.
AB  - OBJECTIVE: To study the occurrence of sick leave and to identify work
      characteristics related to sick leave in patients with early inflammatory joint
      conditions. METHODS: Patients with inflammatory joint conditions present for <12
      months were included in this cross-sectional study. Approximately 85% of patients
      satisfying the criteria participated. Data collection included demographics,
      clinical characteristics, pain, physical functioning and mental health (Short
      Form 36), fatigue, and behavioral coping (Coping of Rheumatic Stressors
      questionnaire). Work characteristics included physical load, psychosocial load,
      job control, and support at work. Outcome was defined as sick leave for >2 weeks
      during the past 6 months. Multiple logistic regression analysis was conducted.
      RESULTS: Sick leave was reported by 54 (26%) of 210 employed patients, with 75%
      of the sick leave periods attributed to joint conditions. Of these 210 patients,
      23% were classified as having rheumatoid arthritis (RA), 35% as having non-RA
      arthritis, and 42% as having inflammatory joint conditions without synovitis.
      Pain, poor physical functioning, and passive behavioral coping were related to
      increased sick leave, whereas diagnostic group was not. Low job control, i.e.,
      low control over planning and pacing of activities within the job, was associated
      with increased sick leave (odds ratio [OR] 2.74), whereas being a supervisor (OR
      0.21) and clerical work (OR 0.45) were related to reduced sick leave. CONCLUSION:
      Substantial sick leave in the past 6 months was reported by 26% of patients with
      early inflammatory joint conditions. Pain, functional limitations, and fewer
      opportunities to determine one's work activities were associated with the
      occurrence of sick leave.

PMID- 18821664
TI  - Employment and disability issues in systemic lupus erythematosus: a review.
AB  - OBJECTIVE: To summarize research pertaining to work disability in lupus patients,
      discuss challenges patients face applying for federal disability assistance in
      the US, and make recommendations for clinical and health policy research.
      METHODS: We searched Medline for articles on work or disability in lupus patients
      and gathered information from the Social Security Administration and the National
      Organization of Social Security Claimants' Representatives. RESULTS: We found 12
      publications with employment-related data; 6 included analysis of predictors of
      work status. The prevalence of inability to work or cessation of work was 15-51%
      in these studies (3-15 years after diagnosis); 20-32% of patients received
      disability benefits. Lower education level, higher disease activity, higher
      disease damage, older age, and higher physical job strain were independent
      predictors of work disability or work cessation in at least 2 studies. Lupus
      patients may be less successful than patients with other diseases when applying
      for federal disability assistance, possibly because medical records may not
      accurately reflect functional limitations. In addition, symptoms contributing to
      work disability (e.g., fatigue, pain, neurocognitive dysfunction) may be
      difficult to assess and quantify. CONCLUSION: Work disability in lupus patients
      is common. Additional research on risk factors for work disability in lupus
      patients and on strategies for reducing the impact of these factors on work
      related activities is needed. The development of better measures and rating
      scales for the symptoms responsible for work disability in lupus patients and
      studies of factors influencing the success of obtaining federal disability
      benefits would also be useful.

PMID- 18821665
TI  - Regulation of pain sensitivity in experimental osteoarthritis by the endogenous
      peripheral opioid system.
AB  - OBJECTIVE: OA is the most common joint disease, affecting 10-15% of people over
      60 years of age. However, up to 40% of individuals with radiologic damage are
      asymptomatic. The purpose of this study was to assess the role of the endogenous
      opioid system in delaying the onset of pain in a murine model of osteoarthritis
      (OA). METHODS: Osteoarthritis was induced by transection of the medial
      meniscotibial ligament. Pain was assessed by monitoring weight distribution and
      activity. At various times postsurgery, the opioid receptor antagonists naloxone
      or peripherally restricted naloxone methiodide were administered, and pain was
      assessed. Levels of the micro-opioid receptor were assessed in the nerves
      innervating the joint by real-time reverse transcription-polymerase chain
      reaction analysis. RESULTS: As in human disease, significant joint damage
      occurred in mice before the onset of pain. To assess whether delayed pain was
      partly the result of increased endogenous opioid function, naloxone or naloxone
      methiodide was administered. Both opioid receptor antagonists led to pain onset 4
      weeks earlier than in vehicle-treated mice, indicating a role of the peripheral
      opioid system in masking OA pain. The expression of the micro-opioid receptor in
      the peripheral nerves supplying the joint was transiently increased in naloxone
      responsive mice. CONCLUSION: These findings indicate that a temporal induction of
      micro-opioid receptors in the early stages of OA delays the onset of pain. This
      is of clinical relevance and may contribute to the assessment of patients
      presenting with pain late in the disease. Furthermore, it may point to a
      mechanism by which the body blocks pain perception in moderate states of tissue
      damage, allowing an increased chance of survival.

PMID- 18821666
TI  - Polymorphisms in the interleukin-1 receptor antagonist and interleukin-6 genes
      affect risk of osteolysis in patients with total hip arthroplasty.
AB  - OBJECTIVE: To determine whether osteolysis after total hip arthroplasty (THA) is
      associated with common polymorphisms within the genes encoding the interleukin-1
      (IL-1) family and IL-6, and to determine whether polymorphisms that are
      associated with osteolysis affect in vitro messenger RNA (mRNA) expression in
      human peripheral blood mononuclear cells (PBMCs) in response to wear particles.
      METHODS: Unrelated white subjects of North European descent (n=612) were
      recruited a mean of 11 years after cemented THA for primary osteoarthritis. Of
      these subjects, 272 had previous osteolysis and 340 had no radiographic evidence
      of osteolysis (control group). Genomic DNA was genotyped for the following single
      nucleotide polymorphisms (SNPs): IL1A +4845, IL1B +3954, IL1B -3737, IL1B -511,
      IL1RA +2018, IL6 -174, IL6 -572, and IL6 -597. In a subset of 60 subjects, PBMCs
      were extracted and stimulated with titanium particles and/or endotoxin, and
      cytokine mRNA expression was measured using quantitative real-time reverse
      transcriptase-polymerase chain reaction. RESULTS: The odds ratio (OR) for
      osteolysis associated with carriage of the IL1RA +2018C allele was 0.66 (95%
      confidence interval [95% CI] 0.48-0.91) (P=0.012). The remaining SNPs were not
      individually associated with osteolysis. The uncommon IL6 haplotype -174G/-572G/
      597A (osteolysis group frequency 2.4%, control group frequency 0.8%) was
      associated with osteolysis (P=0.02, calculated using Haploview software). The
      IL1RA +2018CC genotype was associated with increased mRNA expression compared
      with the +2018TT genotype in both unstimulated and stimulated PBMCs (P=0.01 by
      analysis of variance, after Bonferroni correction). CONCLUSION: The IL1RA +2018C
      allele is associated with a decreased risk of osteolysis after THA and with
      increased IL-1 receptor antagonist mRNA expression in vitro. An uncommon
      haplotype within the promoter region of the gene for IL-6 is positively
      associated with osteolysis.

PMID- 18821667
TI  - The protein tyrosine phosphatase N22 gene is associated with juvenile and adult
      idiopathic inflammatory myopathy independent of the HLA 8.1 haplotype in British
      Caucasian patients.
AB  - OBJECTIVE: To examine single-nucleotide polymorphisms (SNPs) of the protein
      tyrosine phosphatase N22 gene (PTPN22) and to study the relationship between
      PTPN22 and the HLA region in patients with idiopathic inflammatory myopathies
      (IIMs). METHODS: PTPN22 SNPs were assessed in a large, cross-sectional, case
      control study from the UK involving patients with adult or juvenile IIM,
      comprising patients with polymyositis (PM) (n=114), dermatomyositis (DM) (n=102),
      myositis associated with another connective tissue disease (myositis-CTD overlap
      syndrome) (n=64), or juvenile DM (n=101), in comparison with 748 control
      subjects. Seventeen PTPN22 SNPs were genotyped using the Sequenom MassArray iPLEX
      platform. Serotyping for myositis-specific/myositis-associated autoantibodies
      (MSAs/MAAs) was performed by radioimmunoprecipitation. RESULTS: A significant
      association was noted between the R620W variant (rs2476601) and IIM (corrected P
      [Pcorr]=0.0009 versus controls), and specifically with the clinical subgroup of
      PM (Pcorr=0.003 versus controls). A weaker association was noted with juvenile DM
      (Pcorr=0.009 versus controls). No significant associations were noted after
      stratification by serologic subgroups. The association with the R620W variant was
      independent of alleles forming the HLA 8.1 haplotype. No other PTPN22 SNPs were
      associated with IIM. The PTPN22 haplotype containing the R620W T allele was the
      only haplotype significantly associated with IIM. CONCLUSION: The R620W variant
      is a significant risk factor for IIM, independent of the HLA 8.1 haplotype.
      Unlike that in the HLA region, risk is not increased in individuals possessing
      MSAs/MAAs. These results are further evidence that the PTPN22 gene confers
      autoimmune susceptibility.

PMID- 18821668
TI  - Percent true calcium absorption, mineral metabolism, and bone mass in children
      with arthritis: effect of supplementation with vitamin D3 and calcium.
AB  - OBJECTIVE: To assess whether percent true calcium absorption (alpha) is normal
      and whether supplementation with placebo, vitamin D3 (2,000 IU/day), calcium
      (1,000 mg/day), or vitamin D3 plus calcium improves alpha, mineral metabolism, or
      bone mass accrual in children with arthritis. METHODS: Eighteen children received
      all 4 treatments, each for 6 months, in 4 different, randomly assigned orders.
      Changes in levels of 25-hydroxyvitamin D (25[OH]D), 1,25-dihydroxyvitamin D
      (1,25[OH]2D), parathyroid hormone, bone turnover markers, and minerals and in
      bone mineral content were measured. Calcium absorption was determined with a dual
      stable isotope method using 48Ca administered intravenously and 46Ca administered
      orally, and measuring 48Ca, 46Ca, and 42Ca in a 24-hour urine specimen by high
      resolution inductively coupled plasma mass spectroscopy. Wilcoxon's signed rank
      test was used both to identify significant change over the treatment period with
      a given regimen and to compare change with an experimental treatment versus
      change with placebo. RESULTS: Percent true calcium absorption was in the lower
      normal range and did not differ by treatment (mean+/-SD 28.3+/-20.2% with
      placebo, 26.1+/-12.1% with calcium, 19.2+/-11.7% with vitamin D3, and 27.1+/
      16.5% with vitamin D3 plus calcium). With vitamin D3 and vitamin D3 plus calcium
      treatment, 25(OH)D levels were increased and 1,25(OH)2D levels were maintained.
      Serum calcium levels were increased only with vitamin D3 and vitamin D3 plus
      calcium treatment. Levels of bone turnover markers and increases in bone mineral
      content did not differ by treatment. CONCLUSION: The findings of this study
      indicate that percent true calcium absorption is low-normal in children with
      arthritis. Vitamin D3 at 2,000 IU/day increases serum 25(OH)D and calcium levels
      but does not improve bone mass accretion. Calcium at 1,000 mg/day also failed to
      improve bone mass.

PMID- 18821669
TI  - Antibodies to citrullinated alpha-enolase peptide 1 are specific for rheumatoid
      arthritis and cross-react with bacterial enolase.
AB  - OBJECTIVE: To map the antibody response to human citrullinated alpha-enolase, a
      candidate autoantigen in rheumatoid arthritis (RA), and to examine cross
      reactivity with bacterial enolase. METHODS: Serum samples obtained from patients
      with RA, disease control subjects, and healthy control subjects were tested by
      enzyme-linked immunosorbent assay (ELISA) for reactivity with citrullinated alpha
      enolase peptides. Antibodies specific for the immunodominant epitope were raised
      in rabbits or were purified from RA sera. Cross-reactivity with other
      citrullinated epitopes was investigated by inhibition ELISAs, and cross
      reactivity with bacterial enolase was investigated by immunoblotting. RESULTS: An
      immunodominant peptide, citrullinated alpha-enolase peptide 1, was identified.
      Antibodies to this epitope were observed in 37-62% of sera obtained from patients
      with RA, 3% of sera obtained from disease control subjects, and 2% of sera
      obtained from healthy control subjects. Binding was inhibited with homologous
      peptide but not with the arginine-containing control peptide or with 4
      citrullinated peptides from elsewhere on the molecule, indicating that antibody
      binding was dependent on both citrulline and flanking amino acids. The
      immunodominant peptide showed 82% homology with enolase from Porphyromonas
      gingivalis, and the levels of antibodies to citrullinated alpha-enolase peptide 1
      correlated with the levels of antibodies to the bacterial peptide (r2=0.803,
      P<0.0001). Affinity-purified antibodies to the human peptide cross-reacted with
      citrullinated recombinant P gingivalis enolase. CONCLUSION: We have identified an
      immunodominant epitope in citrullinated alpha-enolase, to which antibodies are
      specific for RA. Our data on sequence similarity and cross-reactivity with
      bacterial enolase may indicate a role for bacterial infection, particularly with
      P gingivalis, in priming autoimmunity in a subset of patients with RA.

PMID- 18821670
TI  - Phagocyte-derived reactive oxygen species as suppressors of inflammatory disease.

PMID- 18821671
TI  - Induction of osteoclast-associated receptor, a key osteoclast costimulation
      molecule, in rheumatoid arthritis.
AB  - OBJECTIVE: Osteoclast-associated receptor (OSCAR) is a newly identified
      osteoclast-specific receptor and is of key importance in the process of
      osteoclast costimulation. This study was undertaken to define the role of
      costimulation in osteoclast differentiation during inflammatory arthritis.
      METHODS: OSCAR expression was assessed in the synovium and peripheral blood
      monocytes of patients with rheumatoid arthritis (RA), and associations with
      disease activity were assessed. Serum levels of OSCAR were determined by enzyme
      linked immunosorbent assay. In vitro osteoclast assays were performed to
      characterize the role of OSCAR in human osteoclastogenesis. Cytokine regulation
      of OSCAR was investigated by reverse transcriptase-polymerase chain reaction.
      RESULTS: OSCAR was expressed by osteoclasts at the erosion front and by
      mononuclear cells around synovial microvessels. Flow cytometry revealed enhanced
      expression of OSCAR in peripheral blood monocytes of RA patients as compared with
      healthy controls. OSCAR expression was correlated with disease activity and acute
      phase reactant concentrations. Serum levels of soluble OSCAR were lower in RA
      patients than in healthy controls. Monocytes with high OSCAR expression exhibited
      an enhanced potential to differentiate into osteoclasts. Tumor necrosis factor
      alpha was identified as the main inducer of OSCAR expression in monocytes.
      CONCLUSION: These data suggest that the osteoclast costimulation pathway is
      activated in RA. OSCAR is induced in monocytes of RA patients, facilitating their
      differentiation into osteoclasts and bone resorption.

PMID- 18821672
TI  - Tumor necrosis factor alpha drives cadherin 11 expression in rheumatoid
      inflammation.
AB  - OBJECTIVE: Cadherin 11 expressed on fibroblast-like synoviocytes (FLS) plays a
      key role in normal synovial architecture. The purpose of this study was to
      examine the expression of cadherin 11 in human synovitis. METHODS: Cadherin 11
      expression in synovial biopsy samples from patients with various types of
      arthritis and in lung biopsy samples from patients with interstitial pneumonitis
      (IP) was examined by immunostaining. The regulation of cadherin 11 expression in
      human FLS was assessed by quantitative reverse transcription-polymerase chain
      reaction analysis and Western blotting. Therapeutic modulation of synovial
      cadherin 11 was assessed before and after effective antiinflammatory therapy.
      RESULTS: Abundant staining for cadherin 11 was seen in the intimal lining layer
      and the synovial sublining in inflamed tissues, with discrete staining in
      noninflammatory osteoarthritic (OA) tissues. The pattern and degree of
      immunostaining were similar in tissues from patients with rheumatoid arthritis
      (RA), nonpsoriatic spondylarthritis (SpA), psoriatic arthritis (PsA), and
      inflammatory OA. Clear staining for cadherin 11 was also observed in lung tissues
      from RA-associated IP and idiopathic IP patients, but was very limited in normal
      lung tissue. Cadherin 11 staining correlated strongly with the degree of
      inflammatory infiltration of the tissue, as well as with the C-reactive protein
      level and the erythrocyte sedimentation rate in RA patients. In vitro, cadherin
      11 expression by FLS was consistently up-regulated by tumor necrosis factor alpha
      (TNFalpha) at the protein, but not the messenger RNA, level. Cadherin 11 staining
      in vivo was strongly down-regulated by prednisone treatment in RA patients and by
      TNFalpha blockade in SpA patients. CONCLUSION: Cadherin 11 expression is
      regulated by mediators of inflammation, such as TNFalpha. Since cadherin 11 plays
      an important role in cartilage destruction in experimental arthritis, down
      modulation of cadherin 11 by potent antiinflammatory therapies in humans with
      arthritis may contribute to halting cartilage damage.

PMID- 18821673
TI  - Proteomic characterization of mouse cartilage degradation in vitro.
AB  - OBJECTIVE: To develop proteomics to analyze mouse cartilage degradation and
      correlate transcriptional and translational responses to catabolic stimuli.
      METHODS: Proteomic techniques were used to analyze catabolism in mouse femoral
      head cartilage. Using specific methods to prepare cartilage extracts and
      conditioned media for 2-dimensional polyacrylamide gel electrophoresis and
      subsequent tandem mass spectrometry, we identified novel proteins and fragments
      released into the media of control, interleukin-1alpha (IL-1alpha)-treated, and
      all-trans-retinoic acid (RetA)-treated explants. Fluorescence 2-dimensional
      difference gel electrophoresis was used to quantify protein expression changes.
      We also measured changes in messenger RNA (mRNA) expression to distinguish
      transcriptional and posttranslational regulation of released proteins. RESULTS:
      Differentially abundant proteins in the media of control and treated explants
      included fragments of thrombospondin 1 and connective tissue growth factor. IL
      1alpha stimulated release of the cartilage degeneration marker matrix
      metalloproteinase 3, as well as proteins with uncharacterized roles in cartilage
      pathology, such as neutrophil gelatinase-associated lipocalin. RetA stimulated
      release of the extracellular matrix proteins cartilage oligomeric matrix protein,
      link protein, and matrilin-3 into the media, which was accompanied by a dramatic
      reduction in the corresponding mRNA transcript levels. Gelsolin, which has been
      implicated in cytoskeletal reorganization in arthritis synovial fibroblasts but
      has not been previously associated with cartilage pathology, was regulated by IL
      1alpha and RetA. CONCLUSION: In this first analysis of mouse cartilage
      degradation and protein release using proteomics, we identified proteins and
      fragments, some of which represent novel candidate biomarkers for cartilage
      degradation. Applying these proteomic techniques to wild-type and genetically
      modified mouse cartilage will provide insights into the mechanisms of cartilage
      degeneration.

PMID- 18821674
TI  - Evidence for a pathogenetic role of interleukin-18 in cutaneous lupus
      erythematosus.
AB  - OBJECTIVE: Cutaneous manifestations are the most common clinical features of
      lupus erythematosus (LE). The aim of this study was to analyze differences in the
      inflammatory response of keratinocytes from patients with cutaneous LE (CLE)
      compared with healthy controls. METHODS: Keratinocytes from LE patients and
      controls were cultured from epidermal stem cells of the hair follicle of anagen
      head hairs. Functional responses of keratinocytes to cytokine stimulation were
      determined by flow cytometry and enzyme-linked immunosorbent assay. Biopsy
      samples of lesional skin were analyzed by immunohistochemistry. RESULTS:
      Keratinocytes from CLE patients expressed higher levels of IL-18 receptor on
      their cell surface in response to tumor necrosis factor alpha (TNFalpha) or
      interferon-gamma stimulation. In response to IL-18 stimulation, these cells
      produced large amounts of TNFalpha. Of note, in the presence of IL-18, CLE
      keratinocytes failed to express IL-12. IL-12 has previously been shown to protect
      keratinocytes from ultraviolet irradiation-induced apoptosis. Keratinocytes from
      LE patients were more prone to die upon exposure to IL-18, and this increased
      apoptosis was abrogated by blockade of endogenously produced TNFalpha as well as
      by the addition of exogenous IL-12. IL-18 was highly expressed in biopsy samples
      of lesional skin from CLE patients. CONCLUSION: Our results demonstrate an
      intrinsic difference in the inflammatory response of keratinocytes and indicate
      an autocrine feedback loop involving TNFalpha, IL-18, and IL-12 family members.
      Our results suggest that IL-18 may occupy an important position in the cytokine
      hierarchy in CLE, indicating the potential benefit of a local agent that blocks
      IL-18 activity in the treatment of the manifestations of CLE.

PMID- 18821675
TI  - Immunoglobulin gene polymorphisms are susceptibility factors in clinical and
      autoantibody subgroups of the idiopathic inflammatory myopathies.
AB  - OBJECTIVE: To investigate possible associations of GM and KM markers with adult
      and juvenile forms of the idiopathic inflammatory myopathies (IIMs) in Caucasian
      and African American patients. METHODS: We performed serologic analyses of
      polymorphic determinants associated with immunoglobulin gamma heavy chains (GM)
      and kappa light chains (KM) in large populations of Caucasian patients (n= 514
      [297 adults and 217 children]) and African American patients (n=123 [73 adults
      and 50 children]) with IIM representing the major clinical and autoantibody
      groups. RESULTS: For Caucasian patients with dermatomyositis (DM), the Gm 3 23
      5,13 phenotype was a risk factor in both adults (odds ratio [OR] 2.2, corrected P
      [Pcorr]=0.020) and children (OR 2.2, Pcorr=0.0013). Of interest, the GM 13
      allotype was a risk factor for juvenile DM in both Caucasian subjects (OR 3.9,
      Pcorr<0.0001) and African American subjects (OR 4.8, Pcorr=0.033). However, the
      Gm 1,3,17 5,13,21 phenotype was a risk factor for juvenile DM in Caucasian
      subjects but not African American subjects. Among the IIM autoantibody groups, Gm
      3 23 5,13 was a risk factor in Caucasian adults with anti-Jo-1 autoantibodies (OR
      3.4, Pcorr=0.0031), while the GM 3 allotype was protective in adults with anti
      threonyl-transfer RNA synthetase or anti-U RNP autoantibodies (OR 0.1,
      Pcorr=0.047 and OR 0.2, Pcorr=0.034, respectively). In contrast, GM 6 was a risk
      factor in African American adults with anti-signal recognition particle
      autoantibodies (OR 7.5, Pcorr=0.041). CONCLUSION: These data suggest that
      polymorphic alleles of GM and KM loci are differentially associated with IIM
      subgroups defined by age, ethnicity, clinical features, and autoantibody status,
      and expand the list of immune response genes that are possibly important in the
      pathogenesis of myositis.

PMID- 18821676
TI  - Feasibility of a tetracycline-binding method for detecting synovial fluid basic
      calcium phosphate crystals.
AB  - OBJECTIVE: Basic calcium phosphate (BCP) crystals are common components of
      osteoarthritis (OA) synovial fluid. Progress in understanding the role of these
      bioactive particles in clinical OA has been hampered by difficulties in their
      identification. Tetracyclines stain calcium phosphate mineral in bone. The aim of
      this study was to investigate whether tetracycline staining might be an
      additional or alternative method for identifying BCP crystals in synovial fluid.
      METHODS: A drop of oxytetracycline was mixed with a drop of fluid containing
      synthetic or native BCP, calcium pyrophosphate dihydrate (CPPD), or monosodium
      urate (MSU) crystals and placed on a microscope slide. Stained and unstained
      crystals were examined by light microscopy, with and without a portable broad
      spectrum ultraviolet (UV) pen light. A small set of characterized synovial fluid
      samples were compared by staining with alizarin red S and oxytetracycline.
      Synthetic BCP crystals in synovial fluid were quantified fluorimetrically using
      oxytetracycline. RESULTS: After oxytetracycline staining, synthetic and native
      BCP crystals appeared as fluorescent amorphous aggregates under UV light.
      Oxytetracycline did not stain CPPD or MSU crystals or other particulates.
      Oxytetracycline staining had fewer false-positive test results than did alizarin
      red S staining and could provide estimates of the quantities of synthetic BCP
      crystals in synovial fluid. CONCLUSION: With further validation, oxytetracycline
      staining may prove to be a useful adjunct or alternative to currently available
      methods for identifying BCP crystals in synovial fluid.

PMID- 18821677
TI  - An intriguing relationship between the immune response to citrullinated vimentin
      and the HLA shared epitope: comment on the article by Verpoort et al.

PMID- 18821679
TI  - Reactivation of rheumatoid arthritis after pregnancy: increased phagocyte and
      recurring lymphocyte gene activity.
AB  - OBJECTIVE: Pregnancy is associated with reduced disease activity in rheumatoid
      arthritis (RA) and frequently with disease exacerbation after delivery. This
      study was undertaken to generate a systematic overview of the molecular
      mechanisms related to disease remission and postpartum reactivation. METHODS:
      Transcriptomes of peripheral blood mononuclear cells (PBMCs) were generated from
      RA patients and healthy women by transcription profiling during the third
      trimester and 24 weeks after delivery. For functional interpretation, signatures
      of highly purified immune cells as well as Kyoto Encyclopedia of Genes and
      Genomes pathway annotations were used as a reference. RESULTS: Only minor
      differences in gene expression in PBMCs during pregnancy were found between RA
      patients and controls. In contrast, RA postpartum profiles presented the most
      dominant changes. Systematic comparison with expression signatures of monocytes,
      T cells, and B cells in healthy donors revealed reduced lymphocyte and elevated
      monocyte gene activity during pregnancy in patients with RA and in controls.
      Monocyte activity decreased after delivery in controls but persisted in RA
      patients. Furthermore, analysis of 32 immunologically relevant cellular pathways
      demonstrated a significant additional activation of genes related to adhesion,
      migration, defense of pathogens, and cell activation, including Notch,
      phosphatidylinositol, mTOR, Wnt, and MAPK signaling, in RA patients postpartum.
      CONCLUSION: Our findings indicate that innate immune functions play an important
      role in postpartum reactivation of arthritis. However, this may depend not only
      on the monocyte itself, but also on the recurrence of lymphocyte functions
      postpartum and thus on a critical interaction between both arms of the immune
      system.

PMID- 18821680
TI  - Marked differences in fine specificity and isotype usage of the anti
      citrullinated protein antibody in health and disease.
AB  - OBJECTIVE: Anti-citrullinated protein antibodies (ACPAs) display high association
      with rheumatoid arthritis (RA) and are implicated in its pathogenesis. The
      presence of ACPAs is known to precede the onset of RA. In order to identify the
      features that could confer its pathogenicity, we extensively characterized this
      antibody response in a unique North American native population of patients with
      RA and their unaffected relatives. METHODS: The levels of IgA, IgM, and IgG
      ACPAs, as well as IgM and IgA rheumatoid factor (RF), were measured in serum
      samples obtained from 81 patients with RA and 195 of their unaffected relatives.
      The isotype distribution, the fine specificity of the ACPA response, and its
      association with RF were compared in health and disease. RESULTS: ACPA positivity
      was observed in 19% of the healthy relatives and approximately 91% of the
      patients with RA. ACPA isotype usage was strikingly lower in unaffected relatives
      than in patients with RA (1-2 versus 5-6 isotypes). Fine specificity studies
      showed that reactivity to citrullinated fibrinogen and vimentin was present in
      sera from patients with RA, while it was virtually absent in their unaffected
      relatives. Finally, the ACPA and RF responses were associated in patients with RA
      but were discordant in their healthy relatives. Extended analyses revealed that
      the presence of ACPAs was associated with RA irrespective of RF status, while the
      association of RF with disease relied on its interaction with ACPAs. CONCLUSION:
      The fine specificity and isotype usage of the ACPA response are qualitatively
      different in health and disease. Epitope spreading and expansion of the isotype
      repertoire might be necessary for development of RA, and this could be
      facilitated by the presence of RF antibodies.

PMID- 18821681
TI  - First report of rapidly progressive glomerulonephritis in tumor necrosis factor
      receptor-associated periodic syndrome.

PMID- 18821683
TI  - Highly sensitive B cell analysis predicts response to rituximab therapy in
      rheumatoid arthritis.
AB  - OBJECTIVE: In rheumatoid arthritis (RA), B cell depletion occurs in all patients
      treated with rituximab, but the clinical responses to rituximab are variable. A
      highly sensitive assay was used to test the hypothesis that B cell depletion is
      variable, and that incomplete depletion leads to a poorer outcome. METHODS: Sixty
      patients with active RA unresponsive to anti-tumor necrosis factor agents
      received two 1-gram infusions of rituximab. B cell numbers were measured by
      highly sensitive flow cytometry before and after each infusion and at 3-month
      intervals thereafter. A reduction in B cell levels below 0.0001x10(9)/liter was
      defined as complete depletion (compared with 0.05x10(9)/liter by conventional
      cytometry). Clinical responses were measured using the European League Against
      Rheumatism (EULAR) criteria. RESULTS: At 6 months, 92% of patients had a moderate
      to-good clinical response according to the EULAR criteria. B cells were detected
      in 63% of patients after the first infusion of rituximab (median level
      0.0009x10(9)/liter [range<0.0001-0.0015x10(9)/liter), and these patients had
      poorer clinical outcomes than patients with complete depletion. At 9 months, 82%
      of patients with complete depletion had a moderate-to- good EULAR response,
      compared with 43% of those with partial depletion (P=0.01). At 12 months, 59% of
      complete responders had a moderate-to-good EULAR response, compared with 21% of
      those with partial depletion (P=0.01). Patients in whom B cells were depleted
      only after the second infusion did no better than those in whom depletion was
      never complete and had poorer clinical outcomes than those in whom depletion was
      initially complete. CONCLUSION: This study is the first to show, using a highly
      sensitive analysis, that rituximab therapy is associated with variable diminution
      in B cell numbers. A lack of complete depletion of B cells after 1 infusion was
      associated with a poorer outcome.

PMID- 18821684
TI  - Initiation of the alternative pathway of murine complement by immune complexes is
      dependent on N-glycans in IgG antibodies.
AB  - OBJECTIVE: Collagen antibody-induced arthritis in mice exhibits a requirement for
      amplification by the alternative pathway of complement. Although the alternative
      pathway is activated by spontaneous hydrolysis, it is not known whether this
      pathway can also be initiated directly by IgG antibodies in immune complexes
      (ICs). IgG lacking terminal sialic acid and galactose (G0 IgG) can activate the
      lectin pathway of complement, but it is not known if G0 IgG can also activate the
      classical or alternative pathway. The purpose of this study was to examine the
      mechanism of initiation of the alternative pathway of complement by ICs. METHODS:
      We used adherent ICs containing bovine type II collagen (CII) and 4 monoclonal
      antibodies (mAb) to CII (adCII-IC). C3 activation was measured in the presence of
      sera from wild-type C57BL/6 mice or from mice deficient in informative complement
      components. The mAb were used intact or after enzyme digestion to create G0 IgG
      or to completely remove the N-glycan. RESULTS: Both the classical and alternative
      pathways, but not the lectin pathway, mediated C3 activation induced by the adCII
      IC. Mannose inhibited the alternative pathway-mediated C3 activation but had no
      effect on the classical pathway, and N-glycans in IgG were required by the
      alternative pathway but not the classical pathway. Both the classical and
      alternative pathways mediated C3 activation induced by G0 IgG. Mannose-binding
      lectin bound avidly to G0 IgG, but lectin pathway-mediated C3 activation was only
      slightly increased by G0 IgG. CONCLUSION: The alternative pathway of complement
      is capable of initiating C3 activation induced by adCII-IC and requires the
      presence of N-glycans on the IgG. G0 IgG activates both the classical and
      alternative pathways more strongly than the lectin pathway.

PMID- 18821685
TI  - Neutrophil dysfunction in a family with a SAPHO syndrome-like phenotype.
AB  - SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis, osteitis) is an
      inflammatory disorder of the bone, skin, and joints. We describe a family with
      multiple affected members who segregate a SAPHO syndrome-like phenotype, and we
      report the results of neutrophil studies and candidate gene analysis. We obtained
      written informed consent and a family history and reviewed medical records. We
      collected DNA and sequenced candidate genes, and we performed functional studies
      on neutrophils isolated from the proband and her mother. The pedigree segregated
      chronic osteomyelitis and cutaneous inflammation in a pattern that suggested an
      autosomal-dominant disorder. No coding sequence mutations were detected in
      PSTPIP1, PSTPIP2, LPIN2, SH3BP2, or NCF4. Analysis of neutrophil function in the
      proband, including nitroblue tetrazolium tests, myeloperoxidase assays,
      neutrophil chemotaxis, and neutrophil chemotaxis assays, revealed no identifiable
      abnormalities. However, an abnormality in the luminol, but not the isoluminol,
      respiratory burst assays following stimulation with phorbol myristate acetate
      (PMA) was detected in neutrophils isolated from the affected proband. Internal
      oxidant production was also reduced in the proband and her mother when
      neutrophils were treated with fMLP with or without platelet-activating factor,
      PMA alone, or tumor necrosis factor alpha alone. This family segregates a
      disorder characterized by chronic inflammation of the skin and bone. Functional
      differences in neutrophils exist between affected individuals and controls. The
      biologic significance of this defect remains unknown. Identification of the gene
      defect will help identify an immunologic pathway that, when dysregulated, causes
      inflammation of the skin and bone.

PMID- 18821686
TI  - Brain-immune interactions in arthritis: an integrated systems approach.

PMID- 18821687
TI  - An explanation for the apparent dissociation between clinical remission and
      continued structural deterioration in rheumatoid arthritis.
AB  - OBJECTIVE: Achieving remission is the aim of treatment in rheumatoid arthritis
      (RA). This should represent minimal arthritis activity and ensure optimal disease
      outcome. However, we have previously demonstrated a high prevalence of imaging
      detected synovial inflammation in RA patients who were in clinical remission. The
      purpose of this study was to evaluate the long-term significance of subclinical
      synovitis and its relationship to structural outcome. METHODS: We studied 102 RA
      patients receiving conventional treatment who had been judged by their consultant
      rheumatologist to be in remission, as well as 17 normal control subjects.
      Subjects underwent clinical, laboratory, functional, and quality of life
      assessments over 12 months. In addition to standard radiography of the hands and
      feet, imaging of the hands and wrists was performed with musculoskeletal
      ultrasonography (US) and conventional 1.5 T magnetic resonance imaging (MRI) at
      baseline and 12 months, using validated acquisition and scoring techniques.
      RESULTS: Despite their being in clinical remission, 19% of the patients displayed
      deterioration in radiographic joint damage over the study period. Scores on
      musculoskeletal US synovial hypertrophy, power Doppler (PD), and MRI synovitis
      assessments in individual joints at baseline were significantly associated with
      progressive radiographic damage (P=0.032, P<0.001, and P=0.002, respectively).
      Furthermore, there was a significant association between the musculoskeletal US
      PD score at baseline and structural progression over 12 months in totally
      asymptomatic metacarpophalangeal joints (P=0.004) and 12 times higher odds of
      deterioration in joints with increased PD signal (odds ratio 12.21, P<0.001).
      CONCLUSION: Subclinical joint inflammation detected by imaging techniques
      explains the structural deterioration in RA patients in clinical remission who
      are receiving conventional therapy. Our findings reinforce the utility of imaging
      for the accurate evaluation of disease status and the prediction of structural
      outcome.

PMID- 18821688
TI  - Radiographic findings following two years of infliximab therapy in patients with
      ankylosing spondylitis.
AB  - OBJECTIVE: To evaluate the effect of infliximab on progression of structural
      damage over 2 years in patients with ankylosing spondylitis (AS). METHODS: In the
      Ankylosing Spondylitis Study for the Evaluation of Recombinant Infliximab Therapy
      (ASSERT), a randomized, double-blind, placebo-controlled trial of the efficacy of
      infliximab compared with placebo, 279 patients with active AS received either
      placebo through week 24 and then infliximab 5 mg/kg from week 24 through week 96
      (n=78) or infliximab 5 mg/kg from baseline through week 96, administered every 6
      weeks after a loading dose (n=201; these patients were the focus of the
      radiographic analyses). Radiographic findings in patients from the ASSERT trial
      were indistinguishable from those in a historical control cohort of patients who
      had no prior use of anti-tumor necrosis factor agents (from the Outcome in
      Ankylosing Spondylitis International Study [OASIS] database; n=192). Radiographic
      progression of structural damage from baseline to the 2-year followup was scored
      using the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). All images
      were scored in one batch. RESULTS: Median changes in the mSASSS from baseline to
      year 2 were 0.0 for both the OASIS and the ASSERT cohorts (P=0.541). Mean changes
      in the mSASSS were also similar between the OASIS and ASSERT cohorts (mean+/-SD
      change over 2 years 1.0+/-3.2 and 0.9+/-2.6, respectively). In addition, results
      from sensitivity analyses did not show a statistically significant difference in
      the mSASSS between the OASIS and ASSERT cohorts. CONCLUSION: AS patients who
      received infliximab from baseline through week 96 did not show a statistically
      significant difference in inhibition of structural damage progression at year 2,
      as assessed using the mSASSS scoring system, when compared with radiographic data
      from the historical control OASIS cohort. Improvements in clinical outcomes and
      spinal inflammation have been previously demonstrated with the use of infliximab
      therapy.

PMID- 18821689
TI  - The effects of total knee arthroplasty on physical functioning in the older
      population.
AB  - OBJECTIVE: Clinical research provides convincing evidence that total knee
      arthroplasty (TKA) is safe and improves joint-specific outcomes. However, higher
      level functioning associated with self care and independent living has not been
      studied. Furthermore, most previous studies of the effects of TKA relied on
      relatively small clinical samples. We undertook this study to estimate the
      effects of TKA on 3 levels of physical functioning in a national sample of older
      adults. METHODS: Data were obtained from the Medicare Current Beneficiary Survey
      from 1992 to 2003. Medicare claims data identified participants with
      osteoarthritis of the knee who received TKA (n=259) or no TKA (n=1,816).
      Propensity scores were used to match treatment and no-treatment groups according
      to demographic characteristics, comorbid conditions, and baseline functioning.
      Three levels of physical functioning were examined as outcomes of TKA. These
      levels were represented by items on the Nagi Disability Scale, the Instrumental
      Activities of Daily Living (IADL) Scale, and the Activities of Daily Living (ADL)
      Scale. These items were measured after TKA and at comparable intervals for the no
      treatment group. Average treatment effects were calculated for relevant Nagi
      Disability Scale, IADL Scale, and ADL Scale tasks. RESULTS: Between baseline and
      outcome assessments, TKA recipients improved on all 3 levels of physical
      functioning; the no-treatment group declined. Statistically significant average
      treatment effects for TKA were observed for one or more tasks for each measure of
      physical functioning. CONCLUSION: TKA is associated with sizeable improvements in
      3 levels of physical functioning among elderly Medicare beneficiaries.

PMID- 18821690
TI  - Expression of the CD85j (leukocyte Ig-like receptor 1, Ig-like transcript 2)
      receptor for class I major histocompatibility complex molecules in idiopathic
      inflammatory myopathies.
AB  - OBJECTIVE: Expression of class I major histocompatibility complex (MHC) molecules
      on the surface of muscle cells is a biologic feature of idiopathic inflammatory
      myopathies (IIM). Class I MHC-transgenic mouse models support a causative role
      for class I MHC expression by muscle cells in the pathogenesis of IIM. The muscle
      lesions are characterized by leukocyte infiltration. We undertook this study to
      analyze the expression in muscle lesions of various class I MHC-specific
      receptors on leukocytes and natural killer (NK) cells. METHODS: We generated a
      panel of cell transfectants to control the immunofluorescence analysis of class I
      MHC receptor expression. We then analyzed the expression of CD158 (killer cell Ig
      like receptors [KIRs]) and CD85j (leukocyte Ig-like receptor 1, Ig-like
      transcript 2) on muscle sections prepared from 14 patients with IIM (5 with
      dermatomyositis [DM], 5 with polymyositis [PM], and 4 with sporadic inclusion
      body myositis [IBM]). RESULTS: We could not detect the presence of NK cells in
      inflammatory lesions. However, the class I MHC receptor CD85j, but no KIRs, was
      expressed by inflammatory cells infiltrating muscle lesions in IIM. CONCLUSION:
      CD85j is expressed in PM and sporadic IBM at the sites of partial invasion and in
      DM in perivascular inflammation, paving the way for dissecting the role of CD85j
      in the pathogenesis of inflammatory myopathies.

PMID- 18821691
TI  - Interleukin-6 receptor inhibition with tocilizumab reduces disease activity in
      rheumatoid arthritis with inadequate response to disease-modifying antirheumatic
      drugs: the tocilizumab in combination with traditional disease-modifying
      antirheumatic drug therapy study.
AB  - OBJECTIVE: To examine the efficacy and safety of the humanized anti-interleukin-6
      receptor antibody tocilizumab combined with conventional disease-modifying
      antirheumatic drugs (DMARDs) in patients with active rheumatoid arthritis (RA).
      METHODS: A total of 1,220 patients were randomized (2:1 ratio) in the phase III,
      double-blind, placebo-controlled, multicenter TOWARD (Tocilizumab in Combination
      With Traditional DMARD Therapy) study. Patients remained on stable doses of
      DMARDs and received tocilizumab 8 mg/kg or placebo (control group) every 4 weeks
      for 24 weeks. RESULTS: At week 24, the proportion of patients achieving a
      response according to the American College of Rheumatology criteria for 20%
      improvement (ACR20) was significantly greater in the tocilizumab plus DMARD group
      than in the control group (61% versus 25%; P<0.0001). Secondary end points
      including 50% or 70% improvement (ACR50/70), the Disease Activity Score in 28
      joints (DAS28), DAS28 remission responses (DAS28<2.6), European League Against
      Rheumatism responses, and systemic markers such as the C-reactive protein and
      hemoglobin levels showed superiority of tocilizumab plus DMARDs over DMARDs
      alone. Seventy-three percent of patients in the tocilizumab group had >or=1
      adverse event (AE), compared with 61% of patients in the control group. AEs
      leading to withdrawal from the study were infrequent (4% of patients in the
      tocilizumab group and 2% of those in the control group). Serious AEs occurred in
      6.7% and 4.3% of patients in the tocilizumab and control groups, respectively,
      and serious infections occurred in 2.7% and 1.9%, respectively. Elevations in the
      alanine aminotransferase level, from normal at baseline to >3-fold the upper
      limit of normal, occurred in 4% of patients in the tocilizumab group and 1% of
      those in the control group, and elevated total cholesterol levels were observed
      in 23% and 6% of patients, respectively. Sixteen patients started lipid-lowering
      therapy during the study. Grade 3 neutropenia occurred in 3.7% of patients
      receiving tocilizumab and none of the patients in the control group, and no grade
      4 neutropenia was reported. CONCLUSION: Tocilizumab combined with any of the
      DMARDs evaluated was safe and effective in reducing articular and systemic
      symptoms in patients with an inadequate response to these agents.

PMID- 18821692
TI  - Junctional adhesion molecule C mediates leukocyte adhesion to rheumatoid
      arthritis synovium.
AB  - OBJECTIVE: Leukocyte infiltration into the rheumatoid arthritis (RA) synovium is
      a multistep process in which leukocytes leave the bloodstream and invade the
      synovial tissue (ST). Leukocyte transendothelial migration and adhesion to RA ST
      requires adhesion molecules on the surface of endothelial cells and RA ST
      fibroblasts. This study was undertaken to investigate the role of junctional
      adhesion molecule C (JAM-C) in mediating leukocyte recruitment and retention in
      the RA joint. METHODS: Immunohistologic analysis was performed on RA,
      osteoarthritis (OA), and normal ST samples to quantify JAM-C expression.
      Fibroblast JAM-C expression was also analyzed using Western blotting, cell
      surface enzyme-linked immunosorbent assay, and immunofluorescence. To determine
      the role of JAM-C in leukocyte retention in the RA synovium, in vitro and in situ
      adhesion assays and RA ST fibroblast transmigration assays were performed.
      RESULTS: JAM-C was highly expressed by RA ST lining cells, and its expression was
      increased in OA ST and RA ST endothelial cells compared with normal ST
      endothelial cells. JAM-C was also expressed on the surface of OA ST and RA ST
      fibroblasts. Furthermore, we demonstrated that myeloid U937 cell adhesion to both
      OA ST and RA ST fibroblasts and to RA ST was dependent on JAM-C. U937 cell
      migration through an RA ST fibroblast monolayer was enhanced in the presence of
      neutralizing antibodies against JAM-C. CONCLUSION: Our results highlight the
      novel role of JAM-C in recruiting and retaining leukocytes in the RA synovium and
      suggest that targeting JAM-C may be important in combating inflammatory diseases
      such as RA.

PMID- 18821693
TI  - Interactions of T helper cells with fibroblast-like synoviocytes: up-regulation
      of matrix metalloproteinases by macrophage migration inhibitory factor from both
      Th1 and Th2 cells.
AB  - OBJECTIVE: Interactions of immune cells, such as activated T helper cells, with
      fibroblast-like synoviocytes (FLS) play a crucial role in the joint destruction
      during human rheumatoid arthritis (RA). This study was undertaken to investigate
      the expression of the proinflammatory cytokine macrophage migration inhibitory
      factor (MIF) by T helper cells, and to assess the role of MIF in overexpression
      of matrix metalloproteinases (MMPs) in cocultures of FLS from arthritic mice with
      either Th1 or Th2 cells. METHODS: MIF expression by in vitro-polarized murine Th1
      and Th2 cells was determined using 2 different generation protocols. FLS were
      isolated from the inflamed joints of mice with antigen-induced arthritis. MMP
      expression was analyzed in cocultures of the FLS with T helper cell subsets.
      Effects of MIF were blocked by a neutralizing anti-MIF antibody. In addition,
      analyses were performed on cocultures of either Th1 or Th2 cells with FLS from
      MIF-deficient mice. RESULTS: Both Th1 and Th2 cells expressed high quantities of
      MIF. MMPs were overexpressed by FLS after coculture with both Th1 and Th2 cells.
      Activated T helper cells were more effective than resting cells. Neutralization
      of MIF by an anti-MIF antibody led to a marked reduction in MMP expression in Th1
      and Th2-stimulated FLS. T helper cells generated from MIF-deficient mice
      exhibited a T helper cell-specific cytokine profile comparable with that in wild
      type cells, except in the expression of MIF, but showed an impaired ability to
      stimulate MMP expression in FLS. CONCLUSION: MIF is an important Th1 and Th2 cell
      derived proinflammatory cytokine that stimulates MMP expression in FLS from
      arthritic mice, and therefore inhibition of MIF might be a promising target for
      novel therapeutic strategies in human RA.

PMID- 18821694
TI  - Spinal interleukin-1beta in a mouse model of arthritis and joint pain.
AB  - OBJECTIVE: Pain from arthritis has been associated with peripheral sensitization
      of primary sensory afferents and the development of inflammation at the dorsal
      horns. This study was undertaken to determine whether the role of spinal
      interleukin-1beta (IL-1beta) in central processing of pain is important in the
      development of arthritis. METHODS: Col1-IL-1betaXAT mice and GFAP-IL-1betaXAT
      mice were injected with the feline immunodeficiency virus (FIV) (Cre) vector in
      the right and left temporomandibular joints (TMJs), or in the cisterna magna,
      respectively, to induce IL-1beta expression in the dorsal horns of the spinal
      horn. To inhibit intrathecal IL-1 receptor type I (IL-1RI) signaling, FIV(IL-1Ra)
      vector was injected into the cisterna magna of Col1-IL-1betaXAT mice. The effects
      of IL-1RI receptor inhibition in GFAP-IL-1betaXAT mice were studied in the GFAP
      IL-1betaXAT-IL-1RI(-/-) compound mouse model. Neuroinflammatory, sensory, and
      behavioral changes were evaluated in conjunction with arthritic changes in the
      TMJ, assessed by histopathologic and immunohistochemical analyses. RESULTS:
      Induction of an osteoarthritis-like condition in the TMJ in the Col1-IL-1betaXAT
      mouse model resulted in up-regulation of murine IL-1beta at the dorsal horns.
      Moreover, intrathecal inhibition of IL-1RI in Col1-IL-1betaXAT mice with
      arthritis led to amelioration of joint pathology and attenuation of the attendant
      joint pain. Overexpression of spinal IL-1beta in the recently developed GFAP-IL
      1betaXAT somatic mosaic model of neuroinflammation led to development of
      arthritis-like pathology accompanied by increased pain-like behavior. CONCLUSION:
      Our results indicate that joint pathology and pain are dependent on spinal IL
      1beta, and suggest the presence of a bidirectional central nervous system
      peripheral joints crosstalk that may contribute to the development, expansion,
      and exacerbation of arthritis.

PMID- 18821695
TI  - Vascular endothelial growth factor is highly expressed in muscle tissue of
      patients with polymyositis and patients with dermatomyositis.
AB  - OBJECTIVE: To investigate the expression of vascular endothelial growth factor
      (VEGF) in muscle biopsy specimens and serum from patients with polymyositis and
      patients with dermatomyositis compared with that in healthy control subjects.
      METHODS: Muscle biopsy specimens from 33 patients with polymyositis or
      dermatomyositis and 15 healthy control subjects and serum samples from 56
      patients and 56 healthy control subjects were analyzed. Patients were categorized
      into 3 groups, depending on disease duration and the presence or absence of
      inflammatory infiltrates. The expression of VEGF and the vessel marker CD31 in
      muscle was analyzed by immunohistochemistry, the expression of VEGF messenger RNA
      (mRNA) was analyzed by in situ hybridization, and serum levels of VEGF were
      determined by enzyme-linked immunosorbent assay. RESULTS: Patients with
      polymyositis or dermatomyositis in the early or chronic phase without
      inflammatory infiltrates had a decreased total number of capillaries compared
      with healthy individuals. In patients with early disease without inflammatory
      infiltrates, the number of VEGF-expressing muscle fibers was increased compared
      with that in control subjects, whereas VEGF expression was unchanged in the
      chronic phase of disease. In patients with established disease with inflammatory
      infiltrates, total VEGF expression was high compared with that in healthy control
      subjects. In healthy control subjects, VEGF was expressed in endothelial cells
      and in occasional muscle fibers. VEGF mRNA was expressed in muscle fibers in both
      healthy individuals and patients. The level of serum VEGF was significantly
      increased in patients compared with control subjects. CONCLUSION: Our
      observations support a role of VEGF in the early phases of polymyositis and
      dermatomyositis. A reduced number of capillaries could lead to induction of VEGF
      expression in muscle fibers. Furthermore, differences in molecular expression
      during certain phases of disease may help in the development of specific
      therapeutic algorithms in the treatment of myositis.

PMID- 18821696
TI  - Pathophysiology of rheumatoid arthritis: split or lump?

PMID- 18821697
TI  - Antagonism of the human epidermal growth factor receptor family controls disease
      severity in murine collagen-induced arthritis.
AB  - OBJECTIVE: To evaluate the therapeutic potential of the human epidermal growth
      factor receptor (HER) family inhibitor, herstatin, in an animal model of
      arthritis. METHODS: Constructs of herstatin and modified tissue plasminogen
      activator (tPA)-herstatin were expressed in HEK 293T cells, and secreted protein
      was analyzed by Western blotting. Tissue PA-herstatin adenovirus (Ad-tPA-Her) was
      prepared, and titers established. Gene expression of Ad-tPA-Her was determined by
      polymerase chain reaction using HeLa cells. Pharmacokinetics of gene and protein
      expression in vivo in liver tissue and serum samples were confirmed via
      intravenous administration of Ad-tPA-Her. Clinical signs of disease were
      monitored in arthritic DBA/1 mice after therapeutic administration of Ad-tPA-Her,
      and histologic analysis of hind foot specimens was performed. RESULTS: Native
      herstatin was not secreted in supernatants, while modified tPA-herstatin was
      detected in abundance. HeLa cells stably expressed the tPA-herstatin gene when
      infected with virus. Additionally, tPA-herstatin gene and protein expression was
      observed over time in mice treated with virus. Importantly, Ad-tPA-Her, when
      administered therapeutically to arthritic mice, controlled clinical and
      histologic signs of disease and reduced the number of joints with severe damage.
      CONCLUSION: Our results support the notion that the human epidermal growth factor
      receptor family has a role in the progression of collagen-induced arthritis. The
      novel tPA-herstatin fusion protein could be used as an effective therapeutic tool
      for control of inflammatory disorders involving an angiogenic component.

PMID- 18821698
TI  - Nonspherical femoral head shape (pistol grip deformity), neck shaft angle, and
      risk of hip osteoarthritis: a case-control study.
AB  - OBJECTIVE: To determine whether 2-dimensional measures of femoral head shape and
      angle are associated with hip osteoarthritis (OA). METHODS: We compared cases
      with symptomatic radiographic hip OA with asymptomatic controls with no
      radiographic hip OA. On anteroposterior pelvis radiographs, we measured "pistol
      grip deformity" for each hip (visually categorized as nonspherical,
      indeterminate, or spherical), the femoral head-to-femoral neck ratio as an
      interval measure of femoral head shape, and the femoral neck shaft angle. The
      relative risk of hip OA associated with each feature was estimated using odds
      ratios (ORs) and 95% confidence intervals (95% CIs), adjusted for possible
      confounders using a logistic regression model. RESULTS: Of 1,007 cases, 965 had
      definite radiographic hip OA; of 1,123 controls, 1,111 had no radiographic OA.
      The prevalence of pistol grip deformity in at least 1 hip was 3.61% in controls
      and 17.71% in cases (OR 6.95 [95% CI 4.64-10.41]), and the prevalence of abnormal
      femoral head-to-femoral neck ratio in at least 1 hip was 3.70% in controls and
      24.27% in cases (OR 12.08 [95% CI 8.05-18.15]). The risk of hip OA increased as
      the femoral head-to-femoral neck ratio decreased (P for trend<0.001) and with
      each extreme of neck shaft angle (P<0.05). In cases with unilateral hip OA, the
      prevalence of abnormal femoral head-to-femoral neck ratio in the unaffected hip
      was 2 times greater than that in controls (OR 1.82 [95% CI 1.07-3.07]); in
      contrast, an abnormally low, but not abnormally high, neck shaft angle was more
      common in unaffected hips than in controls (OR 1.79 [95% CI 1.03-3.14]).
      CONCLUSION: Our findings indicate that pistol grip deformity is associated with
      hip OA. The increased prevalence of pistol grip deformity and an abnormally low
      neck shaft angle in unaffected hips of cases with unilateral OA suggests that
      they are risk factors for development of hip OA. However, both a nonspherical
      head shape and an increase in neck shaft angle may occur as a consequence of OA.

PMID- 18821699
TI  - Modulation of peripheral B cell tolerance by CD72 in a murine model.
AB  - OBJECTIVE: B cells play a dominant role in the pathogenesis of several autoimmune
      diseases, including systemic lupus erythematosus. It is not well understood how B
      cell signaling contributes to autoantibody production. The goal of this study was
      to elucidate the role of CD72 in modulating B cell receptor (BCR)-mediated
      tolerogenic signaling and peripheral B cell tolerance. METHODS: A mouse model
      utilizing hen egg lysozyme (HEL) "anergic" B cells was studied. CD72-deficient
      mice carrying the BCR-specific IgHEL and/or soluble HEL (sHEL) transgenes were
      generated by breeding IgHEL-transgenic MD4 mice and/or sHEL-transgenic ML5 mice
      with congenic, CD72-deficient C57BL/6J mice. Normal and anergic B cells were
      isolated for analyses of B cell signaling. Aged wild-type and CD72-deficient mice
      were also examined for autoimmune phenomena. RESULTS: In the absence of CD72,
      anergic B cells inappropriately proliferated and survived in response to
      stimulation with self antigen. Biochemical analyses indicated that in anergic B
      cells, CD72 dominantly down-regulated BCR signaling to limit the antigen-induced
      elevation in [Ca2+]i and the activation of NFATc1, NF-kappaB, MAPK, and Akt.
      Mechanistically, CD72 was associated with, and regulated, the molecular adaptor
      Cbl-b in anergic B cells, suggesting that Cbl-b may play a role in mediating the
      negative effects of CD72 on BCR signaling. Moreover, in aged CD72-deficient mice,
      spontaneous production of antinuclear and anti-double-stranded DNA autoantibodies
      and features of lupus-like autoimmune disease were observed. CONCLUSION: CD72 is
      required to maintain B cell anergy and functions as a regulator of peripheral B
      cell tolerance. Thus, altered CD72 expression may play a role during the
      development of systemic lupus erythematosus.

PMID- 18821701
TI  - Clinical images: incidental retinal vasculopathy: a clue to diagnosing systemic
      disease.

PMID- 18821703
TI  - How antirheumatic drugs protect joints from damage in rheumatoid arthritis.

PMID- 18821704
TI  - Viral infection and reactivation in autoimmune disease.

PMID- 18821705
TI  - Disrupted brain-immune system-joint communication during experimental arthritis.
AB  - OBJECTIVE: To explore the hypothesis that, in parallel with alterations in the
      hypothalamus-pituitary-adrenal axis and the sympathetic nervous system,
      hypothalamic cytokine expression and monoaminergic neurotransmitter
      concentrations are affected during the course of arthritis development induced by
      type II collagen. This hypothesis was based on evidence that acute inflammatory
      processes induce cytokine expression in the brain and affect neuronal activity.
      We also studied whether depletion of hypothalamic noradrenaline can affect
      peripheral joint disease. METHODS: Hypothalamic cytokine gene expression and
      neurotransmitter concentration, parameters of inflammation, and joint innervation
      were evaluated during arthritis development in rats induced by injection of type
      II collagen in Freund's incomplete adjuvant. Noradrenergic neurons in the brain
      were depleted with 6-hydroxydopamine. RESULTS: Transiently increased
      corticosterone levels, followed by increased adrenaline levels and hypothalamic
      interleukin-1beta (IL-1beta) and IL-6 overexpression were observed only during
      the induction phase of the disease. Hypothalamic noradrenaline content was
      increased during the symptomatic phase and was paralleled by a gradual loss of
      noradrenergic fibers in the joints. The positive correlation between hypothalamic
      IL-1beta expression and noradrenaline content in control groups was not observed
      in rats in which arthritis developed. Depletion of hypothalamic noradrenergic
      neurons when arthritis was established did not affect the course of the disease.
      CONCLUSION: The dissociation between hypothalamic cytokine gene expression and
      noradrenergic neuronal activity, the lack of sustained stimulation of the stress
      axes, and the loss of sympathetic signals in the joints indicate a disruption in
      communication between afferent immune messages to the central nervous system and
      2 main efferent antiinflammatory pathways under control of the brain during
      collagen-induced arthritis.

PMID- 18821706
TI  - Induction of an osteoarthritis-like phenotype and degradation of phosphorylated
      Smad3 by Smurf2 in transgenic mice.
AB  - OBJECTIVE: To determine whether Smurf2, an E3 ubiquitin ligase known to inhibit
      transforming growth factor beta (TGFbeta) signaling, is expressed in human
      osteoarthritic (OA) cartilage and can initiate OA in mice. METHODS: Human OA
      cartilage was obtained from patients undergoing knee arthroplasty. Samples were
      graded histologically using the Mankin scale and were examined
      immunohistochemically for Smurf2 expression. A transgene driven by the collagen
      2alpha1 promoter was used to overexpress Smurf2 in mice. Smurf2 overexpression in
      mouse sternal chondrocytes was confirmed by reverse transcription-polymerase
      chain reaction and Western blotting. Changes in articular cartilage area,
      chondrocyte number, and chondrocyte diameter were assessed histomorphometrically
      using OsteoMeasure software. Alterations in type X collagen and matrix
      metalloproteinase 13 (MMP-13) in articular chondrocytes were examined by in situ
      hybridization and immunohistochemistry, respectively. Joint bone phenotypes were
      evaluated by microfocal computed tomography. The effects of Smurf2 overexpression
      on TGFbeta signaling were examined using a luciferase-based reporter and
      immunoprecipitation/Western blotting. RESULTS: Human OA cartilage strongly
      expressed Smurf2 as compared with nonarthritic human cartilage. By 8 months of
      age, Smurf2-transgenic mice exhibited decreased articular cartilage area,
      fibrillation, clefting, eburnation, subchondral sclerosis, and osteophytes.
      Increased expression of type X collagen and MMP-13 were also detected in
      articular cartilage from transgenic mice. Transgenic sternal chondrocytes showed
      reduced TGFbeta signaling as well as decreased expression and increased
      ubiquitination of pSmad3. CONCLUSION: Smurf2 is up-regulated during OA in humans,
      and Smurf2-transgenic mice spontaneously develop an OA-like phenotype that
      correlates with decreased TGFbeta signaling and increased pSmad3 degradation.
      Overall, these results suggest a role of Smurf2 in the pathogenesis of OA.

PMID- 18821707
TI  - Epigallocatechin-3-gallate diminishes CCL2 expression in human osteoblastic cells
      via up-regulation of phosphatidylinositol 3-Kinase/Akt/Raf-1 interaction: a
      potential therapeutic benefit for arthritis.
AB  - OBJECTIVE: To assess the effects of epigallocatechin-3-gallate (EGCG) on
      oncostatin M (OSM)-induced CCL2 synthesis and the associated signaling pathways
      in human osteoblastic cells. The therapeutic effect of EGCG on collagen-induced
      arthritis (CIA) in rats was also studied. METHODS: CCL2 and c-Fos messenger RNA
      expression was analyzed by Northern blotting. The modulating effects of EGCG on
      the activation of Raf-1, Akt, and phosphatidylinositol 3-kinase (PI 3-kinase)
      were examined by coimmunoprecipitation, Western blotting, and PI 3-kinase
      activity assay. Interactions between c-Fos and CCL2 promoter were evaluated by
      electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation
      (ChIP) assay. The effect of EGCG on CIA in rats was examined clinically and
      immunohistochemically. RESULTS: EGCG inhibited OSM-stimulated CCL2 expression in
      primary human osteoblasts and MG-63 cells. In MG-63 cells, EGCG alleviated the
      OSM-induced phosphorylation of Raf-1 at Ser338 but restored the dephosphorylation
      of Raf-1 at Ser259. EGCG increased the activity of PI 3-kinase, the level of
      phosphorylated Akt (Ser473), and binding between Raf-1 and active Akt. EMSA and
      ChIP assay revealed that EGCG attenuated activator protein 1 (AP-1)-CCL2 promoter
      interaction, possibly by reducing c-Fos synthesis. Codistribution of CD68+
      macrophages and CCL2+ osteoblasts in osteolytic areas was obvious in the CIA
      model. Administration of EGCG markedly diminished the severity of CIA, macrophage
      infiltration, and the amount of CCL2-synthesizing osteoblasts. CONCLUSION: By
      stimulating PI 3-kinase activity, EGCG promoted Akt/Raf-1 crosstalk, resulting in
      decreased AP-1 binding to CCL2 promoter, and finally reduced CCL2 production in
      osteoblasts. EGCG alleviated the severity of CIA, probably by suppressing CCL2
      synthesis in osteoblasts to diminish macrophage infiltration. Our data support
      the therapeutic potential of EGCG on arthritis.

PMID- 18821709
TI  - Serum transferrin receptor.
AB  - Transferrin receptors (TfRs) are the conventional pathway by which cells acquire
      iron for physiological requirements. Under iron-deficient conditions there is an
      increased concentration of surface TfR, especially on bone marrow erythroid
      precursors, as a mechanism to sequester needed iron. TfRs are also present in the
      circulation, and the circulating serum TfR (sTfR) level reflects total body TfR
      concentration. Under normal conditions erythroid precursors are the main source
      of sTfR. Disorders of the bone marrow with reduced erythroid precursors are
      associated with low sTfR levels. The sTfR concentration begins to rise early in
      iron deficiency with the onset of iron-deficient erythropoiesis, and continues to
      rise as iron-deficient erythropoiesis progressively worsens, prior to the
      development of anemia. The sTfR level does not increase in anemia of chronic
      inflammation, but is increased when anemia of chronic inflammation is combined
      with iron deficiency. The sTfR level is also increased in patients with expanded
      erythropoiesis, including hemolytic anemias, myelodysplastic syndromes, and use
      of erythropoietic stimulating agents. The ratio of sTfR/ferritin can be used to
      quantify the entire spectrum of iron status from positive iron stores through
      negative iron balance, and is particularly useful in evaluating iron status in
      population studies. The sTfR/log ferritin ratio is valuable for distinguishing
      anemia of chronic inflammation from iron deficiency anemia, whether the latter
      occurs alone or in combination with anemia of chronic inflammation.

PMID- 18821708
TI  - The effect of glucosamine and/or chondroitin sulfate on the progression of knee
      osteoarthritis: a report from the glucosamine/chondroitin arthritis intervention
      trial.
AB  - OBJECTIVE: Osteoarthritis (OA) of the knee causes significant morbidity and
      current medical treatment is limited to symptom relief, while therapies able to
      slow structural damage remain elusive. This study was undertaken to evaluate the
      effect of glucosamine and chondroitin sulfate (CS), alone or in combination, as
      well as celecoxib and placebo on progressive loss of joint space width (JSW) in
      patients with knee OA. METHODS: A 24-month, double-blind, placebo-controlled
      study, conducted at 9 sites in the United States as part of the
      Glucosamine/Chondroitin Arthritis Intervention Trial (GAIT), enrolled 572
      patients with knee OA who satisfied radiographic criteria (Kellgren/Lawrence
      [K/L] grade 2 or grade 3 changes and JSW of at least 2 mm at baseline). Patients
      with primarily lateral compartment narrowing at any time point were excluded.
      Patients who had been randomized to 1 of the 5 groups in the GAIT continued to
      receive glucosamine 500 mg 3 times daily, CS 400 mg 3 times daily, the
      combination of glucosamine and CS, celecoxib 200 mg daily, or placebo over 24
      months. The minimum medial tibiofemoral JSW was measured at baseline, 12 months,
      and 24 months. The primary outcome measure was the mean change in JSW from
      baseline. RESULTS: The mean JSW loss at 2 years in knees with OA in the placebo
      group, adjusted for design and clinical factors, was 0.166 mm. No statistically
      significant difference in mean JSW loss was observed in any treatment group
      compared with the placebo group. Treatment effects on K/L grade 2 knees, but not
      on K/L grade 3 knees, showed a trend toward improvement relative to the placebo
      group. The power of the study was diminished by the limited sample size, variance
      of JSW measurement, and a smaller than expected loss in JSW. CONCLUSION: At 2
      years, no treatment achieved a predefined threshold of clinically important
      difference in JSW loss as compared with placebo. However, knees with K/L grade 2
      radiographic OA appeared to have the greatest potential for modification by these
      treatments.

PMID- 18821710
TI  - Hydroxycarbamide-induced changes in E/beta thalassemia red blood cells.
AB  - In thalassemia, fetal hemoglobin (HbF) augmentation with hydroxycarbamide (also
      known as hydroxyurea) is not always successful. The expected parallel effects on
      red cell (RBC) membrane deformability, cell hydration, and membrane phospholipid
      organization, all important for extending RBC life span and increasing Hb, have
      been infrequently examined. We analyzed these characteristics in 15 nontransfused
      E/beta(0) thalassemia patients treated with HU (mean 10.2 months). Membrane
      deformability and cell hydration mildly improved in association with increased
      HbF levels approaching statistical significance (r = 0.51, P = 0.06). All
      measures improved considerably in splenctomized patients. These findings
      underscore the disappointing results of hydroxyurea treatment in clinical trials
      and the importance of examining the effect on RBC characteristics for the
      development and understanding of HbF-enhancing agents.

PMID- 18821711
TI  - Effect of prophylactic cyclosporine therapy on ADAMTS13 biomarkers in patients
      with idiopathic thrombotic thrombocytopenic purpura.
AB  - Several reports have been published regarding the use of cyclosporine (CSA) in
      the treatment of idiopathic thrombotic thrombocytopenic purpura (TTP). We
      hypothesized that prophylactic CSA therapy may prevent recurrences in patients
      with a history of multiple relapses of TTP. Nineteen patients with idiopathic TTP
      were enrolled on prospective studies at Ohio State University between September
      2003 and May 2007. Patients achieving remission remained on CSA therapy for 6
      months, allowing us to evaluate the efficacy of CSA as prophylactic therapy. CSA
      was administered orally at a dose of 2-3 mg/kg in twice a day divided dose in all
      patients and continued for a total of 6 months. Long-term clinical follow-up with
      serial analysis of ADAMTS13 biomarkers during and after CSA therapy were
      performed to evaluate the efficacy of CSA as a prophylactic therapy. 17/19(89%)
      patients completed 6 months of CSA therapy in a continuous remission. Two
      patients relapsed during therapy with CSA and seven patients relapsed after
      discontinuing CSA therapy. Ten patients have maintained a continuous remission a
      median of 21 months (range, 5-46) after discontinuing CSA. The ADAMTS13 data
      suggest that CSA resulted in a significant increase in the ADAMTS13 activity
      during therapy with CSA. 8/9(89%) relapsing patients had severely deficient
      ADAMTS13 activity (<5%) suggesting this is a significant risk factor for relapse
      of TTP. These data support the hypothesis that prophylactic CSA improves the
      ADAMTS13 activity and may be effective at preventing relapses in patients at risk
      for recurrences of TTP.

PMID- 18821712
TI  - Fifteen years of triple tests in The Netherlands; the life cycle of a screening
      test.
AB  - OBJECTIVE: This report provides an overview of 15 years prenatal screening for
      Down syndrome (DS). METHODS: Between 1991 and 2005, blood samples for the triple
      test were sent for analysis to our laboratory. Test results were considered
      screen-positive for neural tube defects (NTDs) if the serum alpha-1-fetoprotein >
      or = 2.50 MoM for singleton pregnancies or screen-positive for DS if the
      calculated risk was at least 1 in 250. RESULTS: As many as 42 554 tests were
      performed. Data on the pregnancy outcome were available for 30 290 screening
      tests (71.2%). In 1991, most requests (93%) came from the university hospitals;
      thereafter a shift toward midwives occurred. Until 2001, the number of requests
      rose to 3500 a year. Most samples were collected between 15 and 17 weeks of
      gestation. The median age of women for whom a test was requested increased from
      30.5 to 34.5. The detection rate (DR) for DS remained stable over the years
      (80%), with a false positive rate of about 13%. The DR for Trisomy 13, 18, and
      NTD was 50, 68, and 70%, respectively. CONCLUSION: Based on the results of this
      study, the triple test may be considered a fairly good second trimester screening
      test. Here it is shown that health practitioners got more acquainted with the
      test through the years. This may have served the swift introduction of a formal
      national screening program that started in January 2007.

PMID- 18821713
TI  - Spatio-temporal image correlation (STIC) used by general obstetricians is
      marginally clinically effective compared to 2D fetal echocardiography scanning by
      experts.
AB  - OBJECTIVES: To assess the effectiveness of spatio-temporal image correlation
      (STIC) used by general obstetricians as compared with 2D scanning. METHODS: As
      many as 30 pregnant women at 17-21 weeks' gestation were enrolled. 2D ultrasound
      was performed by a fetal echocardiologist; STIC was performed by a general
      obstetrician. Time, accuracy of measurement of diameter of great vessels and
      quality of the pictures obtained by the two methods were compared. RESULTS: The
      mean time required by 2D ultrasound was significantly shorter than that by STIC
      (5.2 +/- 1.9 min vs 9.8 +/- 2.7 min; P < 0.001). The measurement of the diameter
      of the great vessels showed some difference but the mean score of the pictures
      obtained by both methods were not significantly different. By using 2D
      ultrasound, acceptable quality pictures were obtained in 51.9, 44.4 and 51.9% of
      cases for 4-chamber, 5-chamber and 3-vessel views, respectively. Meanwhile by
      using STIC, the percentages were 77.8, 59.3 and 37%. CONCLUSION: Our study
      suggested that STIC used by general obstetricians to check normality of fetal
      cardiac structures at 17-21 weeks' gestation has marginal clinical effectiveness
      when compared to 2D scanning by a fetal echocardiologist, and should need some
      improvement before it can be used as a tool to expand a fetal cardiac screening
      program.

PMID- 18821714
TI  - Small size-specific umbilical vein diameter in severe growth restricted fetuses
      that die in utero.
AB  - BACKGROUND: To study changes in umbilical vein (UV) blood flow velocity, diameter
      and blood flow volume in intrauterine growth retardation (IUGR) fetuses who die
      in utero (IUD-IUGR). METHODS: Twelve singleton IUGR fetuses who died in utero
      below 600 g were included. All cases had abnormal uterine and umbilical arteries
      PI. UV diameter and velocity were measured at the time of diagnosis, and at the
      last exam, within 24 hours prior to intrauterine death. UV flow was calculated
      per unit weight (mL/min/kg) and abdominal circumference (AC) (mL/min/cm). UV
      diameter and velocity were normalized per unit AC. Findings were compared to 14
      severe viable-IUGR and 22 normal gestational age-matched fetuses. RESULTS: UV
      flow (mL/min/kg) was significantly lower in IUD-IUGR compared to viable-IUGR (87
      +/- 30 mL/min/kg) and control fetuses (131 +/- 33 mL/min/kg) both at the first
      (79 +/- 40 mL/min/kg) (P < 0.0001), and at the last exam (54 +/- 29 mL/min/kg) (P
      < 0.0001). No significant longitudinal flow changes were observed. UV velocity/AC
      was significantly reduced both in IUD-IUGR and viable-IUGR compared to normal
      fetuses. UV diameter/AC, was significantly reduced only in IUD-IUGR and not in
      viable-IUGR compared to normal fetuses. CONCLUSIONS: UV flow (mL/min/kg) was
      significantly lower in IUD-IUGR fetuses both versus viable-IUGR and normal
      fetuses. A low flow was due to a decreased UV flow velocity, but also due to a
      reduced vessel size. This significantly smaller UV size observed in IUGR fetuses
      with the worst outcome could be considered a severe prognostic sign because of
      the diagnosis of severe growth restriction.

PMID- 18821715
TI  - A microfluidics approach for the isolation of nucleated red blood cells (NRBCs)
      from the peripheral blood of pregnant women.
AB  - OBJECTIVE: Nucleated red blood cells (NRBCs) have been identified in maternal
      circulation and potentially provide a resource for the monitoring and diagnosis
      of maternal, fetal, and neonatal health and disease. Past strategies used to
      isolate and enrich for NRBCs are limited to complex approaches that result in low
      recovery and less than optimal cell purity. Here we report the development of a
      high-throughput and highly efficient microfluidic device for isolating rare NRBCs
      from maternal blood. MATERIAL AND METHODS: NRBCs were isolated from the
      peripheral blood of 58 pregnant women using a microfluidic process that consists
      of a microfluidic chip for size-based cell separation and a magnetic device for
      hemoglobin-based cell isolation. RESULTS: The microfluidic-magnetic combination
      removes nontarget red blood cells and white blood cells at a very high efficiency
      (approximately 99.99%). The device successfully identified NRBCs from the
      peripheral blood of 58/58 pre-termination samples with a mean of 37.44 NRBC/mL
      (range 0.37-274.36 NRBC/mL). These results were compared with those from previous
      studies. CONCLUSION: The microfluidic device results in an approximate 10- to 20
      fold enrichment of NRBCs over methods described previously. The reliability of
      isolation and the purity of the NRBC product have the potential to enable the
      subsequent application of molecular diagnostic assays.

PMID- 18821716
TI  - Nimesulide associated fulminant hepatic failure.
AB  - PURPOSE: It is controversial whether the non-steroidal inflammatory drug
      nimesulide is associated with severe hepatotoxicity. Our objective was to
      determine whether nimesulide is associated with fulminant hepatic failure.
      METHODS: Retrospective cohort study in the Irish national liver transplant unit.
      All patients who received a liver transplant for fulminant hepatic failure of
      unknown cause, between January 1994 and March 2007, were evaluated. New
      medications started within 6 months prior to transplant were identified.
      Likelihood of association assessed using the Naranjo and Roussel UCLAF Causality
      Assessment Method (RUCAM) scoring systems. RESULTS: Thirty-two patients with sero
      negative, non-paracetamol fulminant hepatic failure, who received an emergency
      liver transplant, were identified. Nimesulide had been started within 6 months in
      6 patients. Five of the six were middle aged females. Nimesulide was assessed as
      probably associated with liver injury in all six cases. CONCLUSIONS: Nimesulide
      was associated with fulminant hepatic failure requiring liver transplant in 6/32
      cases of unknown origin. This association requires further investigation.

PMID- 18821717
TI  - Prescriber adoption of newly approved selective COX-2 inhibitors.
AB  - INTRODUCTION: There is no consistent definition of prescribers who adopt new drug
      treatments early. This study examines if COX-2 inhibitors (coxibs) were
      prescribed by subsets of practitioners and describes GP adoption patterns of
      coxibs and existing NSAIDs over time. METHODS: A population-based drug
      utilisation study using a Dutch medication claims database. Prescribers of
      patients (18+yrs) prescribed an NSAID January 1999-December 2003 were identified.
      Four NSAID categories were chosen reflecting selectivity (coxibs, preferential
      COX-2 inhibitors and non-selective (ns) NSAIDs (sub-categorised as first or
      second line treatment)). The characteristics of prescribers issuing>10
      prescriptions examined were: Type (GP, Specialist, Other); GP NSAID prescribing
      preference ratio (nsNSAIDs/coxib first prescription); coxib (ratio<3); prescriber
      proportion responsible for 100%, 80% and 50% of initiations. Odds Ratios (95%CI)
      were calculated (first-line nsNSAIDs as reference). Plots of prescribing
      proportions by quarter year were examined. RESULTS: NSAID cohorts comprised:
      first-line ns (N=38783); second-line ns (N=1459); COX-2 preferential (N=3107);
      coxib (N=4202) patients. For all four cohorts, GPs were the most common
      prescriber type (>67%); the most frequent prescribing preference was for first
      line nsNSAIDs; 50% percentile prescribing proportions were low (<9%). GPs were
      equally as likely to prescribe coxibs as first-line nsNSAIDs [OR 1.0 (0.9, 1.1)].
      Plots of 100% prescriber proportion for first-line nsNSAIDs and coxibs showed
      convergence; 50th percentile prescriber proportions plots were constant.
      CONCLUSIONS: Small subsets of prescribers accounted for the majority of
      initiations regardless of NSAID type. Further studies are needed on such
      prescribers to inform healthcare policies and encourage participation in post
      marketing safety studies.

PMID- 18821718
TI  - Expanding the phenotype of 22q13.3 deletion: report of a case detected
      prenatally.

PMID- 18821719
TI  - An incomplete trisomy 3 rescue resulting in a marker chromosome and UPD(3)-
      difficulties in interpretation.

PMID- 18821720
TI  - Prenatal sonographic diagnosis of Nager acrofacial dysostosis with unilateral
      upper limb involvement.

PMID- 18821721
TI  - Dietary fats altered nephrotoxicity profile of methylmercury in rats.
AB  - Weanling male Sprague-Dawley rats were administered semi-purified isocaloric diet
      containing soy oil (SO), seal oil (SE), docosahexaenoic acid (DHA), fish oil (FO)
      or lard (LA) for 28 days, and then gavaged with 0, 1 or 3 mg MeHg kg(-1) body
      weight per day and fed the same diet for 14 days. Serum and 24 h urine samples
      were collected on the day of necropsy, and analyzed for markers of kidney
      function and diseases. Kidney slices were analyzed for para-amino-hippurate (PAH)
      and tetraethylammonium (TEA) uptake, total mercury and MeHg content, and examined
      for pathological lesions. Total mercury and MeHg contents increased significantly
      and dose-dependently in all dietary groups. MeHg significantly increased relative
      kidney weight in all groups, serum creatinine in all except SO group, serum uric
      acid in the DHA and LA groups, serum Mg in all except the LA group, and urinary
      protein in the SO group. MeHg significantly decreased serum urea nitrogen in SE,
      FO and LA groups, urinary creatinine in the DHA group, PAH uptake in all except
      the SE group, and TEA uptake in all groups. MeHg caused nephrosis in all dietary
      groups. MeHg also significantly increased neutrophil counts in all except the SE
      group, decreased serum albumin and triglyceride in all except the DHA group, and
      increased serum total cholesterol in all groups, suggesting a nephrotic syndrome
      like outcome. These results confirmed that kidney tubules are major targets of
      MeHg nephrotoxicity. Treatment with dietary fats did not prevent, but rather
      altered the profile of, nephrotoxicity of MeHg in rats.

PMID- 18821722
TI  - Development of a validated liquid chromatography/tandem mass spectrometry method
      for the distinction of thyronine and thyronamine constitutional isomers and for
      the identification of new deiodinase substrates.
AB  - Thyronines (THs) and thyronamines (TAMs) are two groups of endogenous iodine
      containing signaling molecules whose representatives differ from each other only
      regarding the number and/or the position of the iodine atoms. Both groups of
      compounds are substrates of three deiodinase isozymes, which catalyze the
      sequential reductive removal of iodine from the respective precursor molecule. In
      this study, a novel analytical method applying liquid chromatography/tandem mass
      spectrometry (LC-MS/MS) was developed. This method permitted the unequivocal,
      simultaneous identification and quantification of all THs and TAMs in the same
      biological sample. Furthermore, a liquid-liquid extraction procedure permitting
      the concurrent isolation of all THs and TAMs from biological matrices, namely
      deiodinase (Dio) reaction mixtures, was established. Method validation
      experiments with extracted TH and TAM analytes demonstrated that the method was
      selective, devoid of matrix effects, sensitive, linear over a wide range of
      analyte concentrations and robust in terms of reproducible recoveries, process
      efficiencies as well as intra-assay and inter-assay stability parameters. The
      method was applied to study the deiodination reactions of iodinated THs catalyzed
      by the three deiodinase isozymes. With the HPLC protocol developed herein,
      sufficient chromatographic separation of all constitutional TH and TAM isomers
      was achieved. Accordingly, the position of each iodine atom removed from a TH
      substrate in a Dio-catalyzed reaction was backtracked unequivocally. While
      several established deiodination reactions were verified, two as yet unknown
      reactions, namely the phenolic ring deiodination of 3',5'-diiodothyronine (3',5'
      T2) by Dio2 and the tyrosyl ring deiodination of 3-monoiodothyronine (3-T1) by
      Dio3, were newly identified.

PMID- 18821723
TI  - Selective isolation of N-terminal peptides from proteins and their de novo
      sequencing by matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry without regard to unblocking or blocking of N-terminal amino acids.
AB  - We have developed a new method to determine the N-terminal amino acid sequences
      of proteins, regardless of whether their N-termini are modified. This method
      consists of the following five steps: (1) reduction, S-alkylation and
      guanidination for targeted proteins; (2) coupling of sulfo-NHS-SS-biotin to
      N(alpha)-amino groups of proteins; (3) digestion of the modified proteins by an
      appropriate protease followed by oxidation with performic acid; (4) specific
      isolation of N-terminal peptides from digests using DITC resins; (5) de novo
      sequence analysis of the N-terminal peptides by matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) using the
      CAF (chemically assisted fragmentation) method or tandem mass spectrometric
      (MS/MS) analysis according to unblocked or blocked peptides, respectively. By
      employing DITC resins instead of avidin resins used in our previous method
      (Yamaguchi et al., Rapid Commun. Mass Spectrom. 2007; 21: 3329), it has been
      possible to isolate selectively N-terminal peptides from proteins regardless of
      modification of N-terminal amino acids. Here we propose a universal method for N
      terminal sequence analysis of proteins.

PMID- 18821724
TI  - An evaluation of a data mining signal for amyotrophic lateral sclerosis and
      statins detected in FDA's spontaneous adverse event reporting system.
AB  - BACKGROUND: We detected disproportionate reporting of amyotrophic lateral
      sclerosis (ALS) with HMG-CoA-reductase inhibitors (statins) in the Food and Drug
      Administration's (FDA) spontaneous adverse event (AE) reporting system (AERS).
      PURPOSE: To describe the original ALS signal and to provide additional context
      for interpreting the signal by conducting retrospective analyses of data from
      long-term, placebo-controlled clinical trials of statins. METHODS: The ALS signal
      was detected using the multi-item gamma Poisson shrinker (MGPS) algorithm. All
      AERS cases of ALS reported in association with use of a statin were individually
      reviewed by two FDA neurologists. Manufacturers of lovastatin, pravastatin,
      simvastatin, fluvastatin, atorvastatin, cerivastatin, and rosuvastatin were
      requested to provide the number of cases of ALS diagnosed during all of their
      placebo-controlled statin trials that were at least 6 months in duration.
      RESULTS: There were 91 US and foreign reports of ALS with statins in AERS. The
      data mining signal scores for ALS and statins ranged from 8.5 to 1.6. Data were
      obtained from 41 statin clinical trials ranging in duration from 6 months to 5
      years and representing approximately 200,000 patient-years of exposure to statin
      and approximately 200,000 patient-years of exposure to placebo. Nine cases of ALS
      were reported in statin-treated patients and 10 cases in placebo-treated
      patients. CONCLUSIONS: Although we observed a data mining signal for ALS with
      statins in FDA's AERS, retrospective analyses of 41 statin clinical trials did
      not reveal an increased incidence of ALS in subjects treated with a statin
      compared with placebo.

PMID- 18821726
TI  - Computing an NPMLE for a mixing distribution in two closed heterogeneous
      population size models.
AB  - Binomial and geometric mixtures can be used to model data gathered in capture
      recapture surveys of animal populations, removal surveys of harvest populations,
      registrations of disease populations, ecological species census, and so on. To
      compute a nonparametric maximum likelihood estimator for the mixing distribution
      of heterogeneous capture probabilities, we consider a conditional approach and
      use a reliable and fast integrative procedure which combines the EM algorithm to
      increase the likelihood and the vertex-exchange method to update the number of
      support points. A convergent Newtonian algorithm is used in the M-step of the EM
      algorithm.

PMID- 18821725
TI  - Vascular risk and depression in the Hispanic Established Population for the
      Epidemiologic Study of the Elderly (EPESE).
AB  - OBJECTIVE: Although vascular depression has received considerable research
      attention, relatively little research in this area has focused on minority
      samples. This study investigated the association between baseline vascular risk
      factors (VRFs) and risk for elevated depressive symptoms at 2-year follow-up in a
      sample of 964 individuals without significant depressive symptomotology (CES-D <
      12) or cognitive impairment (MMSE>or= 24) at baseline from the Hispanic
      Established Population for the Epidemiologic Study of the Elderly. METHODS: We
      examined the associations between self-reported baseline vascular risk factors
      (chest pain, heart attack, stroke, hypertension, diabetes, and smoking) and a
      composite of these risk factors with elevated depressive symptoms (CES-D >or= 16)
      at 2-year follow-up. RESULTS: Seventy-four (7.7%) of the 964 participants without
      evidence of depression at baseline demonstrated elevated depressive symptoms
      (CESD >or= 16) 2 years later. There was an overall pattern of higher rates of
      elevated depressive symptoms at 2-year follow-up with increasing number of
      vascular risk factors (0 VRFs = 6.4%, 1 VRF = 5.5%, 2 VRFs = 7.7%, and 3 or more
      VRFs = 14.7%). After controlling for demographic variables, physical functioning,
      and other medical conditions, the cumulative vascular risk index was
      significantly associated with elevated depressive symptoms at 2-year follow-up (p
      < 0.05). CONCLUSIONS: Our results suggest vascular conditions may contribute to
      risk for depression over time among Mexican American elders, and this is
      relatively independent of other medical conditions. These findings suggest that
      depression is an additional long-term complication of these common cardiovascular
      disorders.

PMID- 18821727
TI  - Predictors of response to sertraline in patients with major depression.
AB  - OBJECTIVE: Investigation of the characteristics of patients being treated with
      antidepressants would be useful in determining which patients would most likely
      benefit from antidepressant. The purpose of this study was to examine the
      possible predictors of response to sertraline in major depression. METHOD: A
      retrospective cohort analysis was carried out among major depression patients.
      Eighty two patients were identified who were receiving sertraline to treat major
      depression. RESULTS: The cumulative percentage of responders was over 80% after 6
      weeks, and the cumulative percentage of responders was over 80% in patients
      receiving a 75 mg daily dose. Clinical factors, including age, gender, frequency
      of episodes, and family history were examined as possible predictors of response
      to sertraline. On Cox proportional hazards analysis, age, and gender were
      independent predictive factors of improvement with sertraline. The most
      influential factor was age (e(coef) = 1.894), followed by gender (e(coef) =
      0.542); age over 40 years (chi(2) = 5.598, df = 1, p = 0.018) and female gender
      (chi(2) = 7.370, df = 1, p = 0.0066) were significantly associated with
      improvement. CONCLUSIONS: A 6-week treatment period, a 75 mg daily dose, age over
      40 years, and female gender appear to be predictors of response to sertraline in
      major depression. These factors should guide clinicians in determining the choice
      of antidepressant.

PMID- 18821728
TI  - Characterization of natural wax esters by MALDI-TOF mass spectrometry.
AB  - The applicability of matrix-assisted laser desorption/ionization time of flight
      mass spectrometry (MALDI-TOF MS) to the analysis of wax esters (WEs) was
      investigated. A series of metal salts of 2,5-dihydroxybenzoic acid (DHB) was
      synthesized and tested as possible matrices. Alkali metal (Li, Na, K, Rb, Cs) and
      transition metal (Cu, Ag) salts were studied. The matrix properties were
      evaluated, including solubility in organic solvents, threshold laser power that
      should be applied for successful desorption/ionization of WEs, the nature of the
      matrix ions and the mass range occupied by them, and the complexity of the
      isotope clusters for individual metals. Lithium salt of dihydroxybenzoic acid
      (LiDHB) performed the best and matrices with purified lithium isotopes ((6)LiDHB
      or (7)LiDHB) were recommended for WEs. Three sample preparation procedures were
      compared: (1) mixing the sample and matrix in a glass vial and deposition of the
      mixture on a MALDI plate (Mix), (2) deposition of sample followed by deposition
      of matrix (Sa/Ma), and (3) deposition of matrix followed by deposition of sample
      (Ma/Sa). Morphology of the samples was studied by scanning electron microscopy.
      The best sample preparation technique was Ma/Sa with the optimum sample to matrix
      molar ratio 1 : 100. Detection limit was in the low picomolar range. The relative
      response of WEs decreased with their molecular weight, and minor differences
      between signals of saturated and monounsaturated WEs were observed. MALDI spectra
      of WEs showed molecular adducts with lithium [M + Li](+). Fragments observed in
      postsource decay (PSD) spectra were related to the acidic part of WEs [RCOOH +
      Li](+) and they were used for structure assignment. MALDI with LiDHB was used for
      several samples of natural origin, including insect and plant WEs. A good
      agreement with GC/MS data was achieved. Moreover, MALDI allowed higher WEs to be
      analyzed, up to 64 carbon atoms in Ginkgo biloba leaves extract.

PMID- 18821729
TI  - Synthesis and immunosuppressive activity of new cyclolinopeptide A analogs
      modified with beta-prolines.
AB  - Immune response suppressors are used in the medical praxis to prevent graft
      rejection after organ transplantation and in the therapy of some autoimmune
      diseases. As a continuation of our previous work searching for new, effective
      suppressors devoid of toxicity, we present the synthesis, conformational
      analysis, and biological activity of nonapeptides 1-6, analogs of naturally
      existing immunomodulatory peptide CLA. New CLA analogs were modified with (S)
      beta(2)-iso-proline 7 or (S)-beta(3)-homo-proline 8, respectively. The
      conformational influence of the beta-iso-proline and beta-homo-proline building
      blocks was analyzed by NMR spectroscopy. Peptides 1-6 exist as a mixture of four
      isomers due to cis/trans isomerization of the Xxx-Pro peptide bond. The major
      isomers of peptides 1, 3, and 4 contain all peptide bonds of the trans geometry.
      The geometry of the proline-proline bond of the second populated isomer of
      peptides 3 and 4 is cis. The proline-proline peptide bond is cis for the major
      isomers of peptides 2, 5, and 6. The peptides were tested for their ability to
      suppress the proliferative response of mouse splenocytes to T- and B-cell
      mitogens and the secondary humoral immune response to sheep erythrocytes in vitro
      in parallel with a reference drug-cyclosporine A. The immunoregulatory actions of
      the peptides depended on the position and content of proline isomers and were,
      with some exceptions, strongly inhibitory at the highest dose tested (100
      microg/ml). In addition, the peptides were practically devoid of toxicity at that
      dose. In conclusion, the replacement of Pro by beta-Pro may be useful for fine
      tuning CLA immunosuppressive potency and undesirable toxicity.

PMID- 18821730
TI  - Characteristic negative ion fragmentations of deprotonated peptides containing
      post-translational modifications: mono-phosphorylated Ser, Thr and Tyr. A joint
      experimental and theoretical study.
AB  - Peptides and proteins may contain post-translationally modified phosphorylated
      amino acid residues, in particular phosphorylated serine (pSer), threonine (pThr)
      and tyrosine (pTyr). Following earlier work by Lehmann et al., the [M-H]- anions
      of peptides containing pSer and pThr functionality show loss of the elements of
      H3PO4. This process, illustrated for Ser (and using a model system), is CH3CONH
      C(CH2OPO3H2)CONHCH(3) --> [CH3CONHC(==CH2)CONHCH3 (-OPO3H2)] (a) -->
      [CH3CONHC(==CH2)CONHCH3-H]- + H3PO4, a process endothermic by 83 kJ mol(-1) at
      the MP2/6-31++G(d,p)//HF/6-31++G(d,p) level of theory. In addition, intermediate
      (a) may decompose to yield CH3CONHC(==CH2)CONHCH3 + H2PO4 - in a process
      exothermic by 3 kJ mol(-1). The barrier to the transition state for these two
      processes is 49 kJ mol(-1). Characteristic cleavages of pSer and pThr are more
      energetically favourable than the negative ion backbone cleavages of peptides
      described previously. In contrast, loss of HPO3 from [M-H]- is characteristic of
      pTyr. The cleavage [NH2CH(CH2-C6H4-OPO3H-)CO2H] --> [NH2C(CH2-C6H4-O-)CO2H
      (HPO3)] (b) --> NH2CH(CH2-C6H4-O-)CO2H + HPO3 is endothermic by 318 kJ mol(-1) at
      the HF/6-31+G(d)//AM1 level of theory. In addition, intermediate (b) also yields
      NH2CH(CH2-C6H4-OH)CO2H + PO3 - (reaction endothermic by 137 kJ mol(-1)). The two
      negative ion cleavages of pTyr have a barrier to the transition state of 198 kJ
      mol(-1) (at the HF/6-31+G(d)//AM1 level of theory) comparable with those already
      reported for negative ion backbone cleavages.

PMID- 18821731
TI  - Characteristics and comparison of different radiofrequency-only multipole cooling
      cells.
AB  - Various multipole cooling cells are widely used in mass spectrometry for their
      outstanding performance with regard to transmission and cooling effects. Among
      these, radiofrequency (RF)-only quadrupoles, hexapoles, and octopoles are
      routinely used in practical instrumentation. A study of their performance has
      been carried out using a house-built electrospray time-of-flight mass
      spectrometer equipped with three different multipole devices. In addition, a user
      written program was developed using SIMION 7.0 to simulate ion transmission
      characteristics for the different devices utilized. Systematic experiments and
      simulations were performed with an RF-only quadrupole, hexapole, and octopole to
      study their theoretical and practical characteristics.

PMID- 18821732
TI  - Digitized molecular diagnostics: reading disk-based bioassays with standard
      computer drives.
AB  - We report herein a digital signal readout protocol for screening disk-based
      bioassays with standard optical drives of ordinary desktop/notebook computers.
      Three different types of biochemical recognition reactions (biotin-streptavidin
      binding, DNA hybridization, and protein-protein interaction) were performed
      directly on a compact disk in a line array format with the help of microfluidic
      channel plates. Being well-correlated with the optical darkness of the binding
      sites (after signal enhancement by gold nanoparticle-promoted autometallography),
      the reading error levels of prerecorded audio files can serve as a quantitative
      measure of biochemical interaction. This novel readout protocol is about 1 order
      of magnitude more sensitive than fluorescence labeling/scanning and has the
      capability of examining multiplex microassays on the same disk. Because no
      modification to either hardware or software is needed, it promises a platform
      technology for rapid, low-cost, and high-throughput point-of-care biomedical
      diagnostics.

PMID- 18821733
TI  - Direct analysis of fatty acid vapors in breath by electrospray ionization and
      atmospheric pressure ionization-mass spectrometry.
AB  - Real time analysis of human breath is achieved in an atmospheric pressure
      ionization mass spectrometer (API-MS) by negatively charging exhaled vapors via
      contact with an electrospray cloud. The spectrum observed is dominated by a wide
      range of deprotonated fatty acids, including saturated chains up to C14. Above
      C14, the background from cutaneous sources becomes dominant. We also tentatively
      identify a series of unsaturated fatty acids (C7-C10), ketomonocarboxylic acids
      (C6-C10), and a family of aldehydes. The ionization probability of large fatty
      acids increases drastically when the humidity changes from 20% to 95%.
      Accordingly, distinguishing lung vapors (humid) from those in the background
      (dry) requires special precautions. Estimated fatty acid vapor concentrations in
      breath based on our measurements ( approximately 100 ppt) are in fair agreement
      with values expected from blood concentrations in the range for which data are
      available (C3-C6).

PMID- 18821734
TI  - First evidence for occurrence of hydroxylated human metabolites of diclofenac and
      aceclofenac in wastewater using QqLIT-MS and QqTOF-MS.
AB  - The two nonsteroidal anti-inflammatory drugs diclofenac (DCF) and aceclofenac
      (ACF) were monitored for the first time together with their major human phase-I
      metabolites, namely, 4'-hydroxydiclofenac (4'-OH-DCF) and 4'-hydroxyaceclofenac
      (4'-OH-ACF), in untreated and treated sewage samples, collected from a municipal
      wastewater treatment plant which operated a continuous activated sludge (CAS)
      treatment in parallel with membrane bioreactor (MBR) technology. Mean
      concentrations of DCF and 4'-OH-DCF in the influent samples amounted to 349 and
      237 ng/L, respectively, whereas levels of 4'-OH-ACF (average, 59 ng/L) exceeded
      those of its parent drug approximately 2-fold (31 ng/L). Removal rates of 26 and
      56% were achieved for 4'-OH-DCF following CAS and MBR treatment, respectively.
      The most efficient elimination was observed for 4'-OH-ACF in the MBR with only 4%
      of the influent concentration remaining in the treated sewage. Biodegradation
      experiments in batch reactors loaded with mixed liquor demonstrated that ACF
      underwent rapid ester cleavage to liberate DCF, thus constituting a possible
      source of DCF release during biological sewage treatment. Studies on the
      microbial metabolism of DCF (295 Da) in controlled laboratory settings allowed us
      to identify three novel aerobic biotransformation products. Structure elucidation
      by means of ultraperformance liquid chromatography-electrospray ionization-hybrid
      quadrupole-time-of-flight-mass spectrometry in conjunction with H/D-exchange
      experiments unequivocally identified them as deriving from nitrosation of the
      hydroxyl group in the carboxylic acid moiety (324 Da) and from nitration of one
      of the aromatic ring systems (340 Da). A third microbial metabolite emerging in
      the test medium was assigned as dichlorobenzoic acid (190 Da), possibly formed by
      N-dealkylation of DCF and subsequent carboxylation. Taken together, this work
      constitutes the first report on the occurrence of ACF and the human metabolites
      4'-OH-DCF and 4'-OH-ACF in wastewater, underpinning the need of incorporating
      metabolites excreted by humans in monitoring surveys as part of a risk evaluation
      for environmentally relevant pharmaceuticals.

PMID- 18821735
TI  - Interpretation of the electronic spectra of four disilanes.
AB  - Time-dependent density functional theory (TD-DFT/B3LYP(AC)/cc-pVTZ/cc-pVTZ/6
      311G//MP2/cc-pVTZ/cc-pVTZ/6-31G**) has been used to compute vertical excitation
      energies and oscillator strengths of the six low-lying excited states of four
      peralkylated disilanes, hexamethyldisilane (1), hexa-tert-butyldisilane (2), 1,6
      disila[4.4.4]propellane (3), and 1,7-disila[5.5.5]propellane (4). The results
      provide an accurate interpretation of the reported UV absorption spectra of 1-4
      in solution, and for 1 also in the gas phase up to 62,000 cm(-1). The excellent
      agreement of the calculated with the available experimental energies and
      oscillator strengths, and with magnetic circular (MCD) and linear (LD) dichroism,
      gives us confidence that the method will be useful for dependable interpretation
      of the electronic spectra of longer oligosilanes. Although the disilane
      chromophore finds itself in quite different environments in 1-4, its fundamental
      characteristics remain the same, with one important exception. In all four
      compounds, the first valence excited state is due to an electron promotion from
      the sigma(1) HOMO to the pi(1)* orbital, and the second valence excited state to
      a promotion from the sigma(1) HOMO to the sigma(1)* orbital. Surprisingly,
      however, it is only in 2, which has an extraordinarily long SiSi bond, that the
      terminating sigma(1)* orbital is the sigma*(SiSi) antibond, as anticipated, and
      the sigma sigma* transition has the expected very high oscillator strength. In 1,
      3, and 4, the sigma*(SiSi) antibonding orbital is high in energy and does not
      play any role in low-energy excitations. Instead, the terminating orbital of the
      sigma(1)sigma(1)* excitation is represented by Si-alkyl antibonds, combined
      symmetrically with respect to rotation around the SiSi axis and antisymmetrically
      with respect to operations that interchange the two Si atoms. The common
      assumption that the characteristic intense sigma sigma* transitions of longer
      peralkylated oligosilanes extrapolate to the lowest sigma sigma* transition in
      common peralkylated disilanes is incorrect, and only the weak sigma pi*
      transitions extrapolate simply.

PMID- 18821737
TI  - Ni+ reactions with aminoacrylonitrile, a species of potential astrochemical
      relevance.
AB  - The reaction of aminoacrylonitrile, a species of astrochemical interest, with
      Ni(+)((2)D(5/2)) was investigated by means of mass spectrometry techniques and
      density functional theory calculations. The dominant fragmentations in the MIKE
      spectrum correspond to the loss of [C2,N,H3], HCN, and NH3, the loss of H2 being
      very minor. The structure and bonding of the different aminoacrylonitrile-Ni(+)
      complexes were investigated at the B3LYP/6-311G(d,p) level of theory. The same
      approach was employed in our survey of the corresponding potential energy
      surface. This survey indicates that the [C2,N,H3] neutral product can be formed
      either as ketenimine (CH2CNH) or acetonitrile. The formation of the latter is
      significantly more exothermic but involves slightly higher activation barriers;
      so very likely, both isomers are produced along the reaction process. The lost of
      HNC is not competitive with the loss of HCN, because when the former is formed
      the products lie higher in energy and the corresponding mechanisms involve energy
      barriers above the entrance channel. The loss of NH3 is associated with the
      formation of a complex between cyanoacetylene, HCCCN, which is very abundant in
      the interstellar media, and Ni(+).

PMID- 18821738
TI  - Effect of beta-ring rotation on the structures and vibrational spectra of beta
      carotene: density functional theory analysis.
AB  - The effect of beta-ring rotation on the structures and vibrational spectroscopic
      characteristics of beta-carotene, including infrared (IR) intensities and Raman
      activities, is analyzed using density functional theory. Two stable isomers
      having Ci symmetry are obtained. The reversion of bond lengths is ascribed to the
      hyperconjugation effect. The natural bond orbital (NBO) charge analysis suggests
      that the NBO charges of C5 can be used to estimate the degree of pi-electron
      delocalization. These structural variations are used to analyze and assign the
      vibrational spectra. It is concluded that (a) the similar rotational angle
      dependencies of nu1 and nu2 frequencies justify the contribution of C=C stretch
      vibrations to the nu2 mode and explain the same conjugation length dependencies
      of nu1 and nu2 frequencies in polyenes, (b) the nu1 mode can be assigned to the
      C=C stretching in the central part of polyene chain, whereas beta-rings play an
      important role in nu2 and IR1 bands, especially for the all-trans isomer, and (c)
      the transition dipole moment of the calculated IR1 absorption band is relevant to
      the conjugation degree and the crossing angle between the eigenvectors of the
      polyene chain and the C5=C6 stretching vibration. This theoretical analysis,
      together with our previous Raman spectral experiments, suggests that the C6-C7
      bond is easier to be twisted than other parts of beta-carotene molecule and so
      provides an insight into the structures of carotenoids and the properties of
      binding sites in carotenoproteins.

PMID- 18821739
TI  - Molecular structure and antioxidant properties of delphinidin.
AB  - Density functional theory calculations were performed to evaluate the antioxidant
      activity of delphinidin, taking into account its acid/base equilibrium. The
      conformational behavior of both the isolated and the aqueous solvation species
      (simulated with the polarizable continuum model) were analyzed at the B3LYP/6
      31++G(d,p) level, considering the cationic, neutral, and anionic forms, the
      latter two forms consisting of diverse tautomers. The analysis of their electron
      density distributions, using the quantum theory of atoms in molecules, reveals
      several facts that are not in line with their usual Lewis structures. The
      prototropic preferences observed in the gas phase and in solution are similar.
      Thus, in both phases, most stable tautomer of neutral delphinidin is obtained by
      deprotonating the hydroxyl at C4', and the most stable tautomer of the anion is
      obtained by deprotonating the hydroxyls at C4' and C5. All the planar conformers
      obtained display an intramolecular hydrogen bond (IHB) between O3 and H6'.
      Furthermore, the most stable tautomers of the neutral and anionic forms display
      two IHBs between O4' and H3' and H5'. To obtain ionization potentials (IPs) and
      homolytic O-H bond dissociation enthalpies (BDEs), the corresponding radical
      species were optimized at the UB3LYP level. Heterolytic O-H bond dissociation
      enthalpies (proton dissociation enthalpies, PDEs) were also computed. The
      expected important antioxidant activity can be justified from these results. IP,
      O-H BDE, and O-H PDE values suggest that one-step H atom transfer rather than
      sequential proton loss-electron transfer or electron transfer-proton transfer
      would be the most favored mechanisms for explaining the antioxidant activity of
      delphinidin in nonpolar solvents as well as in aqueous solution.

PMID- 18821740
TI  - Inverse temperature dependent lifetimes of transient S(N)2 ion-dipole complexes.
AB  - The association and collisional stabilization of the S(N)2 entrance channel
      complex [Cl(-)...CH3Cl]* is studied in a low-temperature radiofrequency ion trap.
      The temperature dependence of the ternary rate coefficient is measured and a much
      stronger inverse temperature dependence than expected from a simple statistical
      calculation is found. From these data the lifetime of the transient S(N)2 complex
      has been derived as a function of temperature. It is suggested that the inverse
      temperature dependent rates of nonsymmetric S(N)2 reactions are related to the
      observed inverse temperature dependence of the transient ion-dipole complexes.

PMID- 18821741
TI  - Interplay between hydrogen-bond formation and multicenter pi-electron
      delocalization: intramolecular hydrogen bonds.
AB  - The specific case of intramolecular hydrogen bonds assisted by pi-electron
      delocalization is thoroughly investigated using multicenter delocalization
      analysis. The effect of the pi-electron delocalization on the intramolecular
      hydrogen-bond strength is determined by means of the relative molecular energies
      of "open" and "closed" structures, calculated at the B3LYP/6-311++G(d,p) level of
      theory. These relative energies are compared to variations in the multicenter
      electron delocalization indices and covalent hydrogen-bond indices, which are
      shown to correlate very well with the relative strength of the intramolecular
      hydrogen bonds studied. The multicenter electron delocalization indices and
      covalent bond indices have been computed using the quantum theory of atoms in
      molecules approach. The hydrogen bonds are formed with oxygen, nitrogen, or
      sulfur as acceptor atom, which are also the atoms considered to be bonded to the
      donor hydrogen. Malonaldehyde is taken as reference; the substitution of oxygen
      by other atoms at the acceptor and donor positions and the effect of the
      aromaticity have been studied. The results shown here match perfectly with the
      qualitative expectations derived from the resonance models. In addition, they
      provide a quantitative picture of the role played by the pi-electron
      delocalization on the relative strength of intramolecular hydrogen bonds.

PMID- 18821742
TI  - Real-time propagation of the reduced one-electron density matrix in atom-centered
      orbitals: application to multielectron dynamics of carbon clusters C(n) in the
      strong laser pulses.
AB  - We present a time-dependent density functional theory (TDDFT) study on the
      electron dynamics of small carbon clusters C(n) (n = 9, 10) exposed to a linearly
      polarized (LP) or circularly polarized (CP) oscillating electric field of
      ultrafast laser with moderate laser intensity. The multielectron dynamics is
      described by propagating the reduced one-electron density matrix in real-time
      domain. The high harmonic generation (HHG) spectra of emission as well as the
      time evolution of atomic charges, dipole moments and dipole accelerations during
      harmonic generation are calculated. The microscopic structure-property
      correlation of carbon chains is characterized. It is found that the electron
      responses of C(n) to the laser field oscillation become nonadiabatic as the field
      intensity is larger than 1.4 x 10(13) W/cm(2). The nonadiabatic multielectron
      effect is displayed by an explicit fluctuation on the induced atomic charges and
      the instantaneous dipole acceleration and by observing the additional peaks other
      than those predicted from the spectral selection rule in HHG spectra of C(n) as
      well. The origin of these additional peaks is elucidated. The atomic charges of
      C(n) in LP and CP laser pulses experience different type of oscillations as
      expected. In the linear structure C9, the atomic charges at the two ends
      experience larger amplitude oscillations than those near the chain center whereas
      the induced charges on each atom of C10 experience the equal amplitude
      oscillations in the CP laser pulse.

PMID- 18821743
TI  - Hydrogen-bonding interactions in 2-thiophen-3-ylmalonic acid.
AB  - Formation of intra- and intermolecular hydrogen bonds in 2-thiophen-3-ylmalonic
      acid, the precursor of a polythiophene derivative bearing two carboxylic acid
      groups in the side chain, have been examined by Fourier transform infrared (FTIR)
      spectroscopy and ab initio quantum mechanical calculations. Interactions found in
      the FTIR spectra recorded for the melted and solid states are in good agreement
      with results provided by MP2/6-31+G(d,p) calculations on monomers and dimers,
      respectively. Specifically, inter- and intramolecular hydrogen bonds were
      detected in the solid and melted states, respectively. Calculations on dimers
      stabilized by intermolecular hydrogen bonds exclusively and by both intra- and
      intermolecular interactions indicated that the former structures are
      significantly more stable than the latter ones, which is fully consistent with
      experimental observations. On the other hand, intramolecular interactions in
      isolated monomers are favored in the melted state, which is dominated by a
      thermally driven entropic process.

PMID- 18821744
TI  - Wave packet simulation of nonadiabatic dynamics in highly excited 1,3
      dibromopropane.
AB  - We have conducted wave packet simulations of excited-state dynamics of 1,3
      dibromopropane (DBP) with the aim of reproducing the experimental results of the
      gas-phase pump-probe experiment by Kotting et al. [ Kotting, C. ; Diau, E. W.-G.
      ; Solling, T. I. ; Zewail, A. H. J. Phys. Chem. A 2002, 106, 7530 ]. In the
      experiment, DBP is excited to a Rydberg state 8 eV above the ground state. The
      interpretation of the results is that a torsional motion of the bromomethylene
      groups with a vibrational period of 680 fs is activated upon excitation. The
      Rydberg state decays to a valence state, causing a dissociation of one of the
      carbon bromine bonds on a time scale of 2.5 ps. Building the theoretical
      framework for the wave packet propagation around this model of the reaction
      dynamics, the simulations reproduce, to a good extent, the time scales observed
      in the experiment. Furthermore, the simulations provide insight into how the
      torsion motion influences the bond breakage, and we can conclude that the
      mechanism that delays the dissociation is solely the electronic transition from
      the Rydberg state to the valence state and does not involve, for example,
      intramolecular vibrational energy redistribution (IVR).

PMID- 18821745
TI  - IR and Raman characterization of the zincocenes (eta(5)-C5Me5)2Zn2 and (eta(5)
      C5Me5)(eta(1)-C5Me5)Zn.
AB  - The measured Raman and IR spectra of solid, polycrystalline
      bis(pentamethylcyclopentadienyl)dizinc, (eta(5)-C5Me5)2Zn2, 1, and
      bis(pentamethylcyclopentadienyl)monozinc, (eta(5)-C5Me5)(eta(1)-C5Me5)Zn, 8, are
      reported in some detail. The IR spectra of the vapors of 1 and 8 each trapped in
      a solid Ar matrix at 12 K confirm the essentially molecular character of the
      solids. The experimental results have been interpreted with particular reference
      (i) to the corresponding spectra of (68)Zn-enriched samples of the compounds, and
      (ii) to the spectra simulated by density functional theory (DFT) calculations at
      the B3LYP level. The marked differences of structure of 1 and 8 contrast with the
      relatively close similarity of their vibrational spectra, disparities being
      revealed only on detailed scrutiny, including the effects of (68)Zn enrichment,
      and primarily at wavenumbers below 1000 cm(-1). The Zn-Zn stretching motion of 1
      features not as a single, well-defined mode identifiable with intense Raman
      scattering but in several normal modes which respond in varying degrees to (68)Zn
      substitution. A stretching force constant of 1.42 mdyne A(-1) has been estimated
      for the Zn-Zn bond of 1.

PMID- 18821746
TI  - Discovery of novel PPAR ligands by a virtual screening approach based on
      pharmacophore modeling, 3D shape, and electrostatic similarity screening.
AB  - Peroxisome proliferator-activated receptors (PPARs) are important targets for
      drugs used in the treatment of atherosclerosis, dyslipidaemia, obesity, type 2
      diabetes, and other diseases caused by abnormal regulation of the glucose and
      lipid metabolism. We applied a virtual screening workflow based on a combination
      of pharmacophore modeling with 3D shape and electrostatic similarity screening
      techniques to discover novel scaffolds for PPAR ligands. From the resulting 10
      virtual screening hits, five tested positive in human PPAR ligand-binding domain
      (hPPAR-LBD) transactivation assays and showed affinities for PPAR in a
      competitive binding assay. Compounds 5, 7, and 8 were identified as PPAR-alpha
      agonists, whereas compounds 2 and 9 showed agonistic activity for hPPAR-gamma.
      Moreover, compound 9 was identified as a PPAR-delta antagonist. These results
      demonstrate that our virtual screening protocol is able to enrich novel scaffolds
      for PPAR ligands that could be useful for drug development in the area of
      atherosclerosis, dyslipidaemia, and type 2 diabetes.

PMID- 18821747
TI  - The importance of micelle-bound states for the bioactivities of bifunctional
      peptide derivatives for delta/mu opioid receptor agonists and neurokinin 1
      receptor antagonists.
AB  - To provide new insight into the determining factors of membrane-bound peptide
      conformation that might play an important role in peptide-receptor docking and
      further biological behaviors, the dodecylphosphocholine (DPC) micelle-bound
      conformations of bifunctional peptide derivatives of delta-preferring opioid
      agonists and NK1 antagonists (1: Tyr-D-Ala-Gly-Phe-Met-Pro-Leu-Trp-O-3,5-Bzl(CF
      3) 2; 2: Tyr-D-Ala-Gly-Phe-Met-Pro-Leu-Trp-NH-3,5-Bzl(CF 3) 2; 3: Tyr-D-Ala-Gly
      Phe-Met-Pro-Leu-Trp-NH-Bzl) were determined based on 2D NMR studies. Although the
      differences in the primary sequence were limited to the C-terminus, the obtained
      NMR conformations were unexpectedly different for each compound. Moreover, their
      biological activities showed different trends in direct relation to the compound
      specific conformations in DPC micelles. The important result is that not only
      were the NK1 antagonist activities different (the pharmacophore located at the C
      terminus)but the opioid agonist activities (this pharmacophore was at the
      structurally preserved N-terminus) also were shifted, suggesting that a general
      conformational change in the bioactive state was induced due to relatively small
      and limited structural modifications.

PMID- 18821748
TI  - Synthesis and utilization of chiral alpha-methylated alpha-amino acids with a
      carboxyalkyl side chain in the design of novel Grb2-SH2 peptide inhibitors free
      of phosphotyrosine.
AB  - The growth factor receptor-bound protein 2 (Grb2) is an SH2 domain-containing
      docking module that represents an attractive target for anticancer therapeutic
      intervention. To improve the potency and bioavailability of the Grb2-SH2
      inhibitors, the chiral alpha-methyl-alpha-carboxyalkyl amino acid [(alpha-Me)Aa]
      was designed to cover dual structural and functional features separately
      contributed by 1-aminocyclohexanecarboxylic acid (Ac6c) and alpha-aminoadipic
      acid (Adi) in position Y + 1. The enantiopure l(or D)-(alpha-Me)Aa bearing
      various chain length carboxylalkyl side chain was conveniently synthesized by an
      optimized oxazolidinone methodology. The incorporation of (S)-(alpha-Me)Aa into
      the non-pTyr-containing peptide framework with a 5-amino acid sequence binding
      motif of X (-2)-Leu-(3'-substituted-Tyr) (0)-X (+1)-Asn really improved the
      inhibitory activity, affording potent (R)-sulfoxide-bridged cyclic and an open
      chain series of pentapeptide inhibitors of Grb2-SH2 domain (IC 50 = 1.1-5.8
      microM). More significantly, these (alpha-Me)Aa incorporated peptide inhibitors
      showed excellent activities in inhibiting the growth of erbB2-dependent MDA-MB
      453 tumor cell lines with low micromolar IC 50 values, owing to the reduced
      peptidic nature and absence of pTyr or pTyr mimetics.

PMID- 18821749
TI  - 5-N-methylated quindoline derivatives as telomeric g-quadruplex stabilizing
      ligands: effects of 5-N positive charge on quadruplex binding affinity and cell
      proliferation.
AB  - A series of 5-N-methyl quindoline (cryptolepine) derivatives (2a- x) as telomeric
      quadruplex ligands was synthesized and evaluated. The designed ligands possess a
      positive charge at the 5- N position of the aromatic quindoline scaffold. The
      quadruplex binding of these compounds was evaluated by circular dichroism (CD)
      spectroscopy, fluorescence resonance energy transfer (FRET) melting assay,
      polymerase chain reaction (PCR) stop assay, nuclear magnetic resonance (NMR), and
      molecular modeling studies. Introduction of a positive charge not only
      significantly improved the binding ability but also induced the selectivity
      toward antiparallel quadruplex, whereas the nonmethylated derivatives tended to
      stabilize hybrid-type quadruplexes. NMR and molecular modeling studies revealed
      that the ligands stacked on the external G-quartets and the positively charged 5-
      N atom could contribute to the stabilizing ability. Long-term exposure of human
      cancer cells to 2r showed a remarkable cessation in population growth and
      cellular senescence phenotype and accompanied by a shortening of the telomere
      length.

PMID- 18821751
TI  - Ligand-target interaction-based weighting of substructures for virtual screening.
AB  - A methodology is introduced to assign energy-based scores to two-dimensional (2D)
      structural features based on three-dimensional (3D) ligand-target interaction
      information and utilize interaction-annotated features in virtual screening.
      Database molecules containing such fragments are assigned cumulative scores that
      serve as a measure of similarity to active reference compounds. The Interaction
      Annotated Structural Features (IASF) method is applied to mine five high
      throughput screening (HTS) data sets and often identifies more hits than
      conventional fragment-based similarity searching or ligand-protein docking.

PMID- 18821750
TI  - Evaluation of different virtual screening programs for docking in a charged
      binding pocket.
AB  - Virtual screening of small molecules against a protein target often identifies
      the correct pose, but the ranking in terms of binding energy remains a difficult
      problem, resulting in unacceptable numbers of false positives and negatives. To
      investigate this problem, the performance of three docking programs, FRED,
      QXP/FLO, and GLIDE, along with their five different scoring functions, was
      evaluated with the engineered cavity in cytochrome c peroxidase (CCP). This small
      cavity is negatively charged and completely buried from solvent. A test set of 60
      molecules, experimentally identified as 43 "binders" and 17 "non-binders", were
      tested with the CCP binding site. The docking methods' performance is quantified
      by the ROC curve and their reproduction of crystal poses. The effects from
      generation of different ligand tautomers and inclusion of water molecule in the
      cavity are also discussed.

PMID- 18821752
TI  - Mechanistic insight into the initiation step of the coupling reaction of oxetane
      or epoxides and CO2 catalyzed by (salen)CrX complexes.
AB  - The most active and robust current catalysts for the copolymerization of carbon
      dioxide and epoxides or oxetanes, (salen)CrX in conjunction with PPNX (PPN(+) =
      (Ph3P)2N(+)) or n-Bu4NX (X = Cl, N3, CN, NCO), are characterized both in solution
      by infrared spectroscopy and in the solid-state by X-ray crystallography. All
      anions (X) afford six-coordinate chromium(III) PPN(+) or n-Bu4N(+) salts composed
      of trans-(salen)CrX2(-) species. Of the X groups investigated in (salen)CrX,
      chloride is easily displaced by the others, that is, the reaction of (salen)CrCl
      with 2 equiv of N3(-), CN(-), or NCO(-) quantitatively provide (salen)Cr(N3)2(-),
      (salen)Cr(CN)2(-), and (salen)Cr(NCO)2(-), respectively. On the other hand,
      addition of less than 2 equiv of azide to (salen)CrCl leads to a Schlenk (ligand
      redistribution) equilibrium of the three possible anions both in solution and in
      the solid-state as shown by X-ray crystallography and electrospray ionization
      mass spectrometry. It was further demonstrated that all trans-(salen)CrX2(-)
      anions react with the epoxide or oxetane monomers in TCE (tetrachloroethane)
      solution to afford an equilibrium mixture containing (salen)CrX x monomer, with
      the oxetane adduct being thermodynamically more favored. The ring-opening steps
      of the bound cyclic ether monomers by X(-) were examined, revealing the rate of
      ring-opening of the epoxides (cyclohexene oxide and propylene oxide) to be much
      faster than of oxetane, with propylene oxide faster than cyclohexene oxide.
      Furthermore, both X anions in (salen)CrX2(-) were shown to be directly involved
      in monomer ring-opening.

PMID- 18821753
TI  - Oxygen atom transfer from nitrite mediated by Fe(III) porphyrins in aqueous
      solution.
AB  - Aqueous solutions of the iron(III) porphyrin complex FeIII(TPPS) (1, TPPS =
      tetra(4-sulfonatophenyl)-porphyrinato) and nitrite ion react with various
      substrates S to generate the ferrous nitrosyl complex FeII(TPPS)(NO) (2) plus
      oxidized substrate. When S is a water-soluble sulfonated phosphine, the product
      is the resulting monoxide. When air is introduced to the product solutions, 2 is
      rapidly reoxidized to 1; however, even in the absence of air, there is a slow
      regeneration of the ferric species with concomitant production of nitrous oxide.
      Thus, in an anaerobic aqueous environment, FeIII(TPPS) catalyzes oxygen atom
      transfer from nitrite ion to substrates with the eventual formation of N2O.

PMID- 18821754
TI  - Orchestration of concurrent oxidation and reduction cycles for stereoinversion
      and deracemisation of sec-alcohols.
AB  - Black and white are opposites as are oxidation and reduction. Performing an
      oxidation, for example, of a sec-alcohol and a reduction of the corresponding
      ketone in the same vessel without separation of the reagents seems to be an
      impossible task. Here we show that oxidative cofactor recycling of NADP (+) and
      reductive regeneration of NADH can be performed simultaneously in the same
      compartment without significant interference. Regeneration cycles can be run in
      opposing directions beside each other enabling one-pot transformation of racemic
      alcohols to one enantiomer via concurrent enantioselective oxidation and
      asymmetric reduction employing defined alcohol dehydrogenases with opposite
      stereo- and cofactor-preference. Thus, by careful selection of appropriate
      enzymes, NADH recycling can be performed in the presence of NADP (+) recycling to
      achieve overall, for example, deracemisation of sec-alcohols or stereoinversion
      representing a possible concept for a "green" equivalent to the chemical
      intensive Mitsunobu inversion.

PMID- 18821757
TI  - Salt-specific stability and denaturation of a short salt-bridge-forming alpha
      helix.
AB  - The structure of a single alanine-based Ace-AEAAAKEAAAKA-Nme peptide in explicit
      aqueous electrolyte solutions (NaCl, KCl, NaI, and KF) at large salt
      concentrations (3-4 M) is investigated using approximately 1 mus molecular
      dynamics (MD) computer simulations. The peptide displays 71% alpha-helical
      structure without salt and destabilizes with the addition of NaCl in agreement
      with experiments of a somewhat longer version. It is mainly stabilized by direct
      and indirect (" i + 4")EK salt bridges between the Lys and Glu side chains and a
      concomitant backbone shielding mechanism. NaI is found to be a stronger
      denaturant than NaCl, while the potassium salts hardly show influence.
      Investigation of the molecular structures reveals that consistent with recent
      experiments Na (+) has a much stronger affinity to side chain carboxylates and
      backbone carbonyls than K (+), thereby weakening salt bridges and secondary
      structure hydrogen bonds. At the same time, the large I (-) has a considerable
      affinity to the nonpolar alanine in line with recent observations of a large
      propensity of I (-) to adsorb to simple hydrophobes, and thereby "assists" Na (+)
      in its destabilizing action. In the denatured states of the peptide, novel long
      lived (10-20 ns) "loop" configurations are observed in which single Na (+) ions
      and water molecules are hydrogen-bonded to multiple backbone carbonyls. In an
      attempt to analyze the denaturation behavior within the preferential interaction
      formalism, we find indeed that for the strongest denaturant, NaI, the protein is
      least hydrated. Additionally, a possible indication for protein denaturation
      might be a preferential solvation of the peptide backbone by the destabilizing
      cosolute (sodium). The mechanisms found in this work may be of general importance
      to understand salt effects on protein secondary structure stability.

PMID- 18821758
TI  - Thermodynamics of guest-induced structural transitions in hybrid organic
      inorganic frameworks.
AB  - We provide a general thermodynamic framework for the understanding of guest
      induced structural transitions in hybrid organic-inorganic materials. The method
      is based on the analysis of experimental adsorption isotherms. It allows the
      determination of the free energy differences between host structures involved in
      guest-induced transitions, especially hard to obtain experimentally. We discuss
      the general case of adsorption in flexible materials and show how a few key
      quantities, such as pore volumes and adsorption affinities, entirely determine
      the phenomenology of adsorption, including the occurrence of structural
      transitions. On the basis of adsorption thermodynamics, we then propose a
      taxonomy of guest-induced structural phase transitions and the corresponding
      isotherms. In particular, we derive generic conditions for observing a double
      structural transition upon adsorption, often resulting in a two-step isotherm.
      Finally, we show the wide applicability and the robustness of the model through
      three case studies of topical hybrid organic-inorganic frameworks: the hysteretic
      hydrogen adsorption in Co(1,4-benzenedipyrazolate), the guest-dependent gate
      opening in Cu(4,4'-bipyridine)(2,5-dihydroxybenzoate)2 and the CO2-induced
      "breathing" of hybrid material MIL-53.

PMID- 18821759
TI  - A bifunctional monomer derived from lactide for toughening polylactide.
AB  - (6S)-3-Methylene-6-methyl-1,4-dioxane-2,5-dione was synthesized from L-lactide
      and used as the dienophile to prepare spiro[6-methyl-1,4-dioxane-2,5-dione-3,2'
      bicyclo[2.2.1]hept[5]ene] via an exoselective and diastereofacial-selective Diels
      Alder reaction. Polymerizations of this bifunctional lactide derivative were
      successfully carried out under ring-opening and ring-opening metathesis
      polymerization conditions to yield high molecular weight and high Tg polymers. We
      further demonstrated that by incorporating a small percentage of spiro[6-methyl
      1,4-dioxane-2,5-dione-3,2'-bicyclo[2.2.1]hept[5]ene] into poly(1,5
      cyclooctadiene) and copolymerizing it with DL-lactide, novel polymeric alloys of
      PLA can be created that have tremendous improvements in toughness over PLA and
      the corresponding binary blend of PLA and poly(1,5-cyclooctadiene).

PMID- 18821760
TI  - Total synthesis of (+)-lepadin B: stereoselective synthesis of nonracemic
      polysubstituted hydroquinolines using an RC-ROM process.
AB  - This communication describes a new tandem metathesis reaction for which an RC-ROM
      mechanism was experimentally supported. This process was successfully applied to
      the synthesis of cis-fused polyhydroquinolines enabling a short stereoselective
      total synthesis of ent-lepadin B.

PMID- 18821761
TI  - Prominent electron transport property observed for triply fused metalloporphyrin
      dimer: directed columnar liquid crystalline assembly by amphiphilic molecular
      design.
AB  - A triply fused copper porphyrin dimer, when site-specifically modified on its
      periphery with hydrophobic and hydrophilic wedges (1C12/TEG), self-assembles into
      a columnar liquid crystalline (LC) mesophase over a wide-temperature range from 
      17 to 99 degrees C but gives rise to an amorphous solid when modified with only
      hydrophobic (1C12/C12) or hydrophilic wedges (1TEG/TEG). A LC film of 1C12/TEG
      displays at 16 degrees C a top-class one-dimensional electron mobility (0.27
      cm2/V x s), as evaluated from its maximum flash-photolysis time-resolved
      microwave conductivity.

PMID- 18821762
TI  - Realization of SOMO-HOMO level conversion for a TEMPO-dithiolate ligand by
      coordination to platinum(II).
AB  - We developed a TEMPO-bound dithiolate ligand (= tempodt) and its
      Pt(diimine)(dithiolate) complex to realize a unique electronic structure with the
      potential for unprecedented functionalities. The physical properties and
      electronic structures of tempodt, (tempodt)Pt, and their related compounds were
      investigated by cyclic voltammetry, UV-visible spectroscopy, electron spin
      resonance (ESR) spectroscopy, and other techniques. It was revealed that
      (tempodt)Pt showed an unusual electronic structure in which the HOMO level (= pi
      conjugated dithiolate-based orbital) was located above the SOMO level attributed
      to the TEMPO moiety, and that this situation was achieved via a drastic
      electronic structure change of SOMO-HOMO level conversion through complex
      formation. These findings were further supported by an investigation into a one
      electron oxidized (tempodt)Pt and related complexes.

PMID- 18821763
TI  - Enzyme-like acceleration for the hydrolysis of a DNA model promoted by a
      dinuclear Zn(II) catalyst in dilute aqueous ethanol.
AB  - The rates and products of cleavage of methyl (2-chloro-4-nitrophenyl) phosphate
      (2) promoted by a dinuclear Zn(II) complex (3) of 1,3-bis-N,N'(1,5,9
      triazacyclododecyl)propane along with 1 equiv of ethoxide were investigated in
      ethanol solution containing small amounts of water (8 mM <or= [H2O] <or= 2.1 M)
      at 25 degreesC and sspH 7.9. The kinetics of decomposition of 5 x 10(-5) M 2 in
      the presence of varying [3] (0.03 mM <or= [3] <or= 0.12 mM) in ethanol containing
      28 mM water show very strong saturation binding which is analyzed to give fitted
      values for the complex dissociation constant (Kd) and maximum catalytic rate
      constant (kcatmax) of 3.2 x 10(-8) M and 1.47 x 10(-3) s(-1). Product analysis
      indicates that the reaction in ethanol containing 28 mM and 2.1 M water produces
      46% and 93% of the hydrolysis product (methyl phosphoric acid), with the
      remainder being ethanolysis product (ethyl methyl phosphate). Analysis of the
      kinetics of the reaction at 28 mM water indicates that second order rate constant
      for the catalytic reaction, given as kcatmax/Kd, is 4.6 x 104 M(-1) s(-1), is a
      factor of 8.4 x 10(10) larger than the second order rate constant (k2EtO) for the
      ethoxide promoted reaction of 2 in ethanol (5.5 +/- 0.3) x 10(-7) M(-1) s(-1). A
      more detailed analysis that considers the relative acidities of water and ethanol
      in ethanol solvent indicates that at sspH 7.9, the ethanolysis is accelerated by
      2.3 x 10(14) times relative to the computed ethoxide reaction at that sspH, while
      the hydrolysis is accelerated by >or=1.6 x 10(17) times relative to the
      background hydroxide reaction, suggesting that complex 3 promotes the hydrolysis
      at least 1000 times more effectively than ethanolysis.

PMID- 18821764
TI  - Syntheses of alpha- and beta-C-glucopyranosyl serines from a common intermediate.
AB  - A versatile synthesis leading to either C-linked alpha- or beta-glucopyranosyl
      serines is presented from a common, advanced synthetic intermediate. Cyclization
      of the penultimate carbinol onto the alkene and methanolysis of the lactone
      yields selectively the alpha-linkage. A transposition of these last steps leads
      to the beta-linked isomer selectively.

PMID- 18821765
TI  - TEMPO/NaIO4-SiO2: a catalytic oxidative rearrangement of tertiary allylic
      alcohols to beta-substituted alpha,beta-unsaturated ketones.
AB  - The novel catalytic method for the oxidative rearrangement of tertiary allylic
      alcohols to beta-substituted alpha,beta-unsaturated ketones is described.
      TEMPO/NaIO4-SiO2 causes facile and efficient oxidative rearrangement of various
      acyclic substrates as well as medium-sized and macrocyclic substrates.

PMID- 18821766
TI  - Highly diastereoselective addition of lithio vinyl sulfoxides to N-sulfinimines:
      an entry to enantiopure 3-sulfinyl-2,5-cis-dihydropyrroles.
AB  - The addition of enantiopure alpha-metalated vinyl and dienyl sulfoxides to
      enantiomerically pure N-sulfinimines takes place with high diastereoselectivity
      primarily directed by the N-sulfinimine sulfur. The resulting allylic amines have
      been further transformed into highly functionalized 3-sulfinyl and 3-sulfonyl 2,5
      cis-dihydropyrroles by reaction with electrophiles.

PMID- 18821767
TI  - Total synthesis of (+)-lepadin F.
AB  - An enantioselective total synthesis of (+)-lepadin F is described. The synthetic
      sequence features an intermolecular aza-[3 + 3] annulation, homologation of a
      vinylogous amide via Eschenmoser's episulfide contraction, and a highly
      stereoselective hydrogenation essential for achieving the 1,3-anti relative
      stereochemistry at C2 and C8a.

PMID- 18821768
TI  - Influence of processing on quality parameters of strawberries.
AB  - To determine the effects of different processing steps, such as enzymatic
      treatment of the mash and pasteurization, on selected quality parameters,
      strawberries were processed to juices and purees. To identify the processing
      steps causing the highest losses, samples were taken after each step, and
      ascorbic acid, total phenols, anthocyanins, and antioxidant capacity were
      analyzed. To assess the antioxidant capacity, three different methods were
      applied: the trolox equivalent antioxidant capacity (TEAC), the ferric reducing
      antioxidant power (FRAP), and the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay,
      showing correlation coefficients of 0.889 to 0.948. The antioxidant capacity
      decreased with processing steps except heat treatment, which partly caused an
      increase due to the formation of antioxidant active products. The content of
      ascorbic acid, in comparison to that in the frozen strawberries, decreased
      significantly during the processing of the fruit to puree by 77%. In the pressed
      cloudy juices, the loss of ascorbic acid was 37%. The decline of phenolic
      compounds, measured as total polyphenols and anthocyanins, was smaller (between
      30-40%). Pressing and pasteurization were the most critical steps for the
      decrease of these compounds. The enzymatic treatment of the mash within 90 min
      supported the release of secondary plant metabolites, while ascorbic acid is
      reduced up to 20%.

PMID- 18821769
TI  - Obtention and characterization of phenolic extracts from different cocoa sources.
AB  - The aim of this study was to evaluate several cocoa sources to obtain a rich
      phenol extract for use as an ingredient in the food industry. Two types of
      phenolic extracts, complete and purified, from different cocoa sources (beans,
      nibs, liquor, and cocoa powder) were investigated. UPLC-MS/MS was used to
      identify and quantify the phenolic composition of the extracts, and the Folin
      Ciocalteu and vanillin assays were used to determine the total phenolic and
      flavan-3-ol contents, respectively. The DPPH and ORAC assays were used to measure
      their antioxidant activity. The results of the analysis of the composition of the
      extracts revealed that the major fraction was procyanidins, followed by flavones
      and phenolic acids. From the obtained results, the nib could be considered the
      most interesting source for obtaining a rich phenolic cocoa extract because of
      its rich phenolic profile content and high antioxidant activity in comparison
      with the other cocoa sources.

PMID- 18821770
TI  - Does white wine qualify for French paradox? Comparison of the cardioprotective
      effects of red and white wines and their constituents: resveratrol, tyrosol, and
      hydroxytyrosol.
AB  - It is generally believed that the French paradox is related to the consumption of
      red wine and not other varieties of wine, including white wine or champagne. Some
      recent studies have indicated that white wine could also be as cardioprotective
      as red wine. The present investigation compares the cardioprotective abilities of
      red wine, white wine, and their principal cardioprotective constituents.
      Different groups of rats were gavaged with red wine, white wine, resveratrol,
      tyrosol, and hydroxytyrosol. Red wine and its constituent resveratrol and white
      wine and its constituents tyrosol and hydroxytyrosol all showed different degrees
      of cardioprotection as evidenced by their abilities to improve postischemic
      ventricular performance, reduce myocardial infarct size and cardiomyocyte
      apoptosis, and reduce peroxide formation. It was discovered in this study that
      although each of the wines and their components increased the enzymatic
      activities of the mitochondrial complex (I-IV) and citrate synthase, which play
      very important roles in oxidative phosphorylation and ATP synthesis, some of the
      groups were more complex-specific in inducing the activity compared to the other
      groups. Cardioprotective ability was further confirmed by increased expression of
      phospho-Akt, Bcl-2, eNOS, iNOS, COX-1, COX-2, Trx-1, Trx-2, and HO-1. The results
      of this study suggest that white wine can provide cardioprotection similar to red
      wine if it is rich in tyrosol and hydroxytyrosol.

PMID- 18821771
TI  - Applications of high-resolution solid-state NMR spectroscopy in food science.
AB  - The principal applications of high-resolution solid-state NMR spectroscopy, in
      the field of food science, are reviewed, after a short general introduction,
      mainly focusing on the potential of these investigations, which are, today,
      routine tools for resolving technological problems. Selected examples of the
      applications in the field of food science of high-resolution solid-state NMR
      spectroscopy both in (13)C and in (1)H NMR particularly illustrative of the
      results obtainable are reported in some detail.

PMID- 18821773
TI  - A stabilizing alpha/beta-hydrophobic core greatly contributes to
      hyperthermostability of archaeal [P62A]Ssh10b.
AB  - The hyperthermophilic Ssh10b from Sulfolobus shibatae is a member of the Sac10b
      family, which has been postulated to play a role in chromosomal organization in
      Archaea. Ssh10b is capable of significantly constraining negative DNA supercoils
      at elevated temperatures. In this study, the solution structure of the dimeric
      P62A mutant Ssh10b ([P62A]Ssh10b) was determined by multidimensional NMR
      spectroscopy. The backbone 15N dynamics, H/D exchange with and without the
      denaturant GdmSCN, and chemical and thermal denaturation experiments were
      performed to investigate the molecular basis of high thermostability of
      [P62A]Ssh10b. Data analysis has revealed an alpha/beta-hydrophobic core
      consisting of two alpha-helices and one beta-sheet which are stabilized by
      cooperative hydrophobic and hydrogen-bonding interactions. This stabilizing
      alpha/beta-hydrophobic core of [P62A]Ssh10b exhibiting highly restricted internal
      motions is composed of residues having highly protected amide protons which
      exchange with solvent mostly by means of a global unfolding process. The K40N
      mutation greatly destabilizes the mutant [P62A]Ssh10b because this mutation
      disturbs the packing of alpha-helix against the beta-sheet reducing the stability
      of the alpha/beta-hydrophobic core in the mutant protein. In comparison with
      homologous mesophilic and thermophilic proteins, it can be presumed that the
      stabilizing alpha/beta-hydrophobic core in the [P62A]Ssh10b structure greatly
      contributes to the high thermostability of the protein.

PMID- 18821774
TI  - Monitoring water reactions during the S-state cycle of the photosynthetic water
      oxidizing center: detection of the DOD bending vibrations by means of Fourier
      transform infrared spectroscopy.
AB  - Photosynthetic water oxidation takes place in the water-oxidizing center (WOC) of
      photosystem II (PSII). To clarify the mechanism of water oxidation, detecting
      water molecules in the WOC and monitoring their reactions at the molecular level
      are essential. In this study, we have for the first time detected the DOD bending
      vibrations of functional D 2O molecules during the S-state cycle of the WOC by
      means of Fourier transform infrared (FTIR) difference spectroscopy. Flash-induced
      FTIR difference spectra upon S-state transitions were measured using the PSII
      core complexes from Thermosynechococcus elongatus moderately deuterated with D 2
      (16)O and D 2 (18)O. D 2 (16)O-minus-D 2 (18)O double difference spectra at
      individual S-state transitions exhibited six to eight peaks arising from the D
      (16)OD/D (18)OD bending vibrations in the 1250-1150 cm (-1) region. This
      observation indicates that at least two water molecules, not in any deprotonated
      forms, participate in the reaction at each S-state transition throughout the
      cycle. Most of the peaks exhibited clear counter peaks with opposite signs at
      different transitions, reflecting a series of reactions of water molecules at the
      catalytic site. In contrast, negative bands at approximately 1240 cm (-1) in the
      S 2 --> S 3, S 3 --> S 0, and possibly S 0 --> S 1 transitions, for which no
      clear counter peaks were found in other transitions, can be interpreted as
      insertion of substrate water into the WOC from a water cluster in the proteins.
      The characteristics of the weakly D-bonded OD stretching bands were consistent
      with the insertion of substrate from internal water molecules in the S 2 --> S 3
      and S 3 --> S 0 transitions. The results of this study show that FTIR detection
      of the DOD bending vibrations is a powerful method for investigating the
      molecular mechanism of photosynthetic water oxidation as well as other enzymatic
      reactions involving functional water molecules.

PMID- 18821775
TI  - Structural basis for ligand binding and specificity in adrenergic receptors:
      implications for GPCR-targeted drug discovery.
AB  - Crystal structures of engineered human beta 2-adrenergic receptors (ARs) in
      complex with an inverse agonist ligand, carazolol, provide three-dimensional
      snapshots of the disposition of seven transmembrane helices and the ligand
      binding site of an important G protein-coupled receptor (GPCR). As expected, beta
      2-AR shares substantial structural similarities with rhodopsin, the dim-light
      photoreceptor of the rod cell. However, although carazolol and the 11- cis
      retinylidene moiety of rhodopsin are situated in the same general binding pocket,
      the second extracellular (E2) loop structures are quite distinct. E2 in rhodopsin
      shows beta-sheet structure and forms part of the chromophore-binding site. In the
      beta 2-AR, E2 is alpha-helical and seems to be distinct from the receptor's
      active site, allowing a potential entry pathway for diffusible ligands. The
      structures, together with extensive structure-activity relationship (SAR) data
      from earlier studies, provide insight about possible structural determinants of
      ligand specificity and how the binding of agonist ligands might alter receptor
      conformation. We review key features of the new beta 2-AR structures in the
      context of recent complementary work on the conformational dynamics of GPCRs. We
      also report 600 ns molecular dynamics simulations that quantified beta 2-AR
      receptor mobility in a membrane bilayer environment and show how the binding of
      an agonist ligand, adrenaline (epinephrine), causes conformational changes to the
      ligand-binding pocket and neighboring helices.

PMID- 18821776
TI  - Switch from conventional to distributed kinetics in the bacteriorhodopsin
      photocycle.
AB  - Below 195 K, the bacteriorhodopsin photocycle could not be adequately described
      with exponential kinetics [Dioumaev, A. K., and Lanyi, J. K. (2007) Proc. Natl.
      Acad. Sci. U.S.A. 104, 9621-9626] but required distributed kinetics, previously
      found in hemoglobin and myoglobin at temperatures below the vitrification point
      of the surrounding solvent. The aim of this study is to determine which factors
      cause the switch from this low-temperature regime to the conventional kinetics
      observed at ambient temperature. The photocycle was monitored by time-resolved
      FTIR between 180 and 280 K, using the D96N mutant. Depending on the temperature,
      decay and temporal redistribution of two or three intermediates (L, M, and N)
      were observed. Above approximately 245 K, an abrupt change in the kinetic
      behavior of the photocycle takes place. It does not affect the intermediates
      present but greatly accelerates their decay. Below approximately 240 K, a kinetic
      pattern with partial decay that cannot be explained by conventional kinetics, but
      suggesting distributed kinetics, was dominant, while above approximately 250 K,
      there were no significant deviations from exponential behavior. The approximately
      245 K critical point is >/=10 K below the freezing point of interbilayer water,
      and we were unable to correlate it with any FTIR-detectable transition of the
      lipids. Therefore, we attribute the change from distributed to conventional
      kinetics to a thermodynamic phase transition in the protein. Most probably, it is
      related to the freezing and thawing of internal fluctuations of the protein,
      known as the dynamic phase transition, although in bacteriorhodopsin the latter
      is usually believed to take place at least 15 K below the observed critical
      temperature of approximately 245 K.

PMID- 18821777
TI  - Identification of cell surface markers to differentiate rat endothelial and
      fibroblast cells using lectin arrays and LC-ESI-MS/MS.
AB  - Vascular endothelial cells located at the inner surface of blood vessels are a
      key component in angiogenesis and are employed as a primary cell type in the
      study of angiogenesis. These endothelial cells are, however, easily contaminated
      with fibroblast cells, which are located in proximity to the endothelial cells,
      during their isolation from tissue. It is thus important to find markers to
      distinguish the two cell types. In the present work, lectin arrays were prepared
      using aldehyde-terminated self-assembled monolayers (SAMs) and utilized to
      explore cell surface carbohydrate expression patterns on endothelial and
      fibroblast cells. It was found that the lectins Griffonia simplicifolia II (GS
      II) and Ulex europaeus agglutinin I (UEA I) selectively bind to rat fibroblast
      cells and not to rat endothelial cells. GS II-binding glycoproteins on fibroblast
      cells, which are potential cell surface markers to differentiate endothelial and
      fibroblast cells, were captured on a GS II lectin column and analyzed by LC-ESI
      MS/MS. Six candidate cell surface glycoproteins were identified. Differential
      expression was confirmed by Western blot analysis for two of these proteins,
      lysosome-associated membrane glycoprotein-1 and transmembrane glycoprotein NMB.

PMID- 18821778
TI  - Speciation analysis of gadolinium-based MRI contrast agents in blood plasma by
      hydrophilic interaction chromatography/electrospray mass spectrometry.
AB  - The first analytical method for simultaneous speciation analysis of five of the
      most important gadolinium-based magnetic resonance imaging (MRI) contrast agents
      in blood plasma samples was developed. Gd-DTPA (Magnevist), Gd-BT-DO3A
      (Gadovist), Gd-DOTA (Dotarem), Gd-DTPA-BMA (Omniscan), and Gd-BOPTA (Multihance)
      were separated by hydrophilic interaction liquid chromatography (HILIC) and
      detected with electrospray mass spectrometry (ESI-MS). Spiking experiments of
      blank plasma with Magnevist and Gadovist were performed to determine the
      analytical figures of merit and the recovery rates. The limits of detection
      ranged from 1 x 10 (-7) to 1 x 10 (-6) mol/L depending on the ionization
      properties of the individual compounds, and limits of quantification ranged from
      5 x 10 (-7) to 5 x 10 (-6) mol/L. The linear concentration range comprised 2
      orders of magnitude. With application of this method, blood plasma samples of 10
      healthy volunteers, with Magnevist or Gadovist medication, were analyzed for Gd
      DTPA and Gd-BT-DO3A, respectively. The obtained results were successfully
      validated with inductively coupled plasma-optical emission spectroscopy (ICP
      OES).

PMID- 18821779
TI  - Mass spectrometry analysis of phosphopeptides after peptide carboxy group
      derivatization.
AB  - A nearly 100% yield peptide carboxy group derivatization method was offered to
      largely enhance phosphopeptide ionization efficiency. This method, adopting 1-(2
      pyrimidyl) piperazine (PP) as the derivatization reagent, shows several
      advantages such as good reproducibility, ease of handling, rapid reaction time,
      and no side reaction. PP derivatization improves the hydrophobicities, p I
      values, and gas-phase basicities of peptides especially those of phosphopeptides.
      In the matrix assisted laser desorption ionization (MALDI) source, the ionization
      efficiencies of four synthetic phosphopeptides were increased by 50-101 times
      while that of three nonphosphopeptides were 10-40-fold. In the electrospray
      ionization (ESI) source, PP-derivatized phosphopeptides also gave much higher
      ionization efficiency improvements than nonphosphopeptides. When this method was
      applied to much more complex mixtures, tryptic BSA digests spiked with one single
      phosphopeptide in different molar ratios, the signal intensity of this
      phosphopeptide always had the largest increment among all those peptides.
      Obviously, this easily manipulated as well as highly specific method provides a
      promising tool for high-throughput phosphoproteome research.

PMID- 18821780
TI  - Equivalence of the different Cm- and Cs-term expressions used in liquid
      chromatography and a geometrical model uniting them.
AB  - It is shown that all C m and C s expressions ever established in the literature
      are intrinsically fully identical and can be derived from a simple parallel plug
      flow model. Analytically solving this model yields C m- and C s-term expressions
      that exactly correspond to the expressions obtained via either the method of
      moments (general rate model) or via Giddings' nonequilibrium theory. This holds
      for open-tubular as well as packed and monolithic columns. From this equivalence,
      a set of convenient "translation" expressions could be established, enabling a
      swift transition between the different C m- and C s-term expressions that
      currently coexist in literature. The link with the parallel plug flow model
      provides a good physical insight into the assumptions underlying the general rate
      model (e.g., a plug flow in the flow-through pores) and in the physical meaning
      of the different parameters involved in it. The parallel plug flow model also
      allows us to illustrate the difference between the zone and the phase retention
      factor and between the intraparticle diffusion coefficient and the effective
      diffusion coefficient used in the general rate model. These differences are
      subtle, but as they can have a large impact, they constitute important potential
      sources of confusion currently obscuring the modeling of HPLC columns.

PMID- 18821781
TI  - Multiplex mass spectrometric genotyping of single nucleotide polymorphisms
      employing pyrrolidinyl peptide nucleic acid in combination with ion-exchange
      capture.
AB  - A new ion-exchange capture technique is introduced for label-free sample
      preparation in single nucleotide polymorphism (SNP) genotyping. The DNA sample is
      hybridized with a new pyrrolidinyl peptide nucleic acid (PNA) probe and treated
      with a strong anion exchanger. The complementary PNA.DNA hybrid is selectively
      captured by the anion exchanger in the presence of noncomplementary or
      unhybridized PNA, allowing direct detection of the hybridization event on the
      anion exchanger by MALDI-TOF mass spectrometry after simple washing. The high
      specificity of the pyrrolidinyl PNA allows simultaneous multiplex SNP typing to
      be carried out at room temperature without the need for enzyme treatment or
      heating. Exemplary applications of this technique, in the identification of meat
      species in feedstuffs and in multiplex SNP typing of the human IL-10 gene
      promoter region are demonstrated, clearly suggesting the potential for much
      broader applications.

PMID- 18821782
TI  - Identification of adducts formed in the reactions of 5'-acetoxy-N'
      nitrosonornicotine with deoxyadenosine, thymidine, and DNA.
AB  - N'-Nitrosonornicotine (NNN) is the most prevalent of the carcinogenic tobacco
      specific nitrosamines found in all tobacco products. Previous studies have
      demonstrated that cytochrome P450-mediated 5'-hydroxylation of NNN is a major
      metabolic pathway leading to mutagenic products, but to date, DNA adducts formed
      by this pathway have been only partially characterized, and there have been no
      studies reported on adducts formed with bases other than dGuo. Because adducts
      with dAdo and dThd have been identified in the DNA of the livers of rats treated
      with the structurally related carcinogen N-nitrosopyrrolidine, we investigated
      dAdo and dThd adduct formation from 5'-acetoxyNNN (3), a stable precursor to 5'
      hydroxyNNN (2). Reaction of 3 with dAdo gave diastereomeric products, which were
      identified by their spectral properties and LC-ESI-MS/MS-SRM analysis as N(6)-[5
      (3-pyridyl)tetrahydrofuran-2-yl]dAdo (9). This adduct was further characterized
      by NaBH(3)CN reduction to N(6)-[4-hydroxy-4-(3-pyridyl)but-1-yl]dAdo (17). A
      second dAdo adduct was identified, after NaBH(3)CN treatment, as 6-[2-(3
      pyridyl)pyrrolidin-1-yl]purine-2'-deoxyriboside (18). Reaction of 3 with dThd,
      followed by NaBH(3)CN reduction, gave O(2)-[4-(3-pyridyl)-4-hydroxybut-1
      yl]thymidine (11). Adducts 9, 11, 17, and 18 were all identified by LC-ESI-MS/MS
      SRM comparison to synthetic standards. The reaction of 3 with calf thymus DNA was
      then investigated. The DNA was enzymatically hydrolyzed to deoxyribonucleosides,
      and the resulting mixture was treated with NaBH(3)CN and analyzed by LC-ESI-MS/MS
      SRM. Adducts 11, 17, and 18, as well as the previously identified dGuo adducts,
      were identified. The results of this study provide a more comprehensive picture
      of DNA adduct formation by the quantitatively important 5'-hydroxylation pathway
      of NNN and will facilitate investigation of the presence of these adducts in
      laboratory animals treated with NNN or in people who use tobacco products.

PMID- 18821783
TI  - Activated epidermal growth factor receptor as a novel target in pancreatic cancer
      therapy.
AB  - Pancreatic cancer is one of the most fatal among all solid malignancies. Targeted
      therapeutic approaches have the potential to transform cancer therapy as
      exemplified by the success of several tyrosine kinase inhibitors. Prompted by
      this, comprehensive profiling of tyrosine kinases and their substrates was
      carried out using a panel of low passage pancreatic cancer cell lines. One of the
      pancreatic cancer cell lines, P196, which showed dramatic upregulation of
      tyrosine kinase activity as compared to non-neoplastic cells, was systematically
      studied using a quantitative proteomic approach called stable isotope labeling
      with amino acids in cell culture (SILAC). A careful analysis of activated
      tyrosine kinase pathways revealed aberrant activation of epidermal growth factor
      receptor pathway in this cell line. Mouse xenograft based studies using EGFR
      inhibitor erlotinib confirmed EGFR pathway to be responsible for proliferation in
      these tumors. By a systematic study across low passage pancreatic cancer cell
      lines and mice carrying pancreatic cancer xenografts, we have demonstrated
      activated epidermal growth factor receptor as an attractive candidate for
      targeted therapy in a subset of pancreatic cancers. Further, we propose
      immunohistochemical labeling of activated EGFR (pEGFR (1068)) as an efficient
      screening tool to select patients who are more likely to respond to EGFR
      inhibitors.

PMID- 18821785
TI  - First-principles-based calculations of vibrational normal modes in polyatomic
      materials with translational symmetry: application to PETN molecular crystal.
AB  - Numerical studies of vibrational energy transport and associated (non)linear
      infrared and Raman response in polyatomic materials require knowledge of the
      multidimensional vibrational potential-energy surface and the ability to perform
      normal-mode analysis on that potential. The presence of translational symmetry,
      as in crystals, leads to the observed dispersion of the unit cell normal modes
      and has to be accounted for in calculations of energy transfer rates and other
      spectroscopic quantities. Here we report on the implementation of a computational
      approach that combines the generalized supercell method and density functional
      theory electronic structure calculations to investigate the vibrational structure
      in translationally symmetric materials containing relatively large numbers of
      atoms in the unit cell (58 atoms in the present study). The method is applied to
      calculate the phonon and vibron dispersion relations and the vibrational density
      of states in pentaerythritol tetranitrate (PETN) molecular crystal which is an
      important energetic material. The results set the stage for future investigations
      of vibrational energy transport and associated nonlinear spectroscopic signatures
      in this class of materials.

PMID- 18821788
TI  - Hydrated excess proton at water-hydrophobic interfaces.
AB  - The behavior of the hydrated excess proton is investigated at the water-vapor,
      water-hydrophobic wall, and water-carbon tetrachloride interfaces through
      molecular dynamics simulations using the third-generation multistate empirical
      valence bond model (MS-EVB3). The MS-EVB3 simulations show a surface preference
      of the excess proton at the water-vapor interface, consistent with the discovery
      of this effect using an earlier version of the MS-EVB model (Petersen et al. J.
      Phys. Chem. B 2004, 108, 14804) and with the experimental results. The preference
      of the hydrated excess proton for other water-hydrophobic interfaces is also
      analyzed for the first time. The hydrated proton structures and charge defect
      delocalization effects at these interfaces are discussed in detail. By
      decomposing the free energy profiles into the internal energy and entropic
      contributions, the thermodynamic (free energy) driving forces for the surface
      preference of the excess proton are also elaborated. These results indicate that
      the "rigid" hydrated proton structures at all the interfaces are energetically
      (as opposed to entropically) stabilized due to the "amphiphilic" nature of the
      hydrated excess proton, resulting in its overall interfacial concentration
      enhancement. The effects of acid concentration and nuclear quantization are also
      explored.

PMID- 18821786
TI  - Anesthetic modulation of protein dynamics: insight from an NMR study.
AB  - Mistic (membrane integrating sequence for translation of integral membrane
      protein constructs) comprises the four-alpha-helix bundle scaffold found in the
      transmembrane domains of the Cys-loop receptors that are plausible targets for
      general anesthetics. Nuclear magnetic resonance (NMR) studies of anesthetic
      halothane interaction with Mistic in dodecyl phosphocholine (DPC) micelles
      provide an experimental basis for understanding molecular mechanisms of general
      anesthesia. Halothane was found to interact directly with Mistic, mostly in the
      interfacial loop regions. Although the presence of halothane had little effect on
      Mistic structure, (15)N NMR relaxation dispersion measurements revealed that
      halothane affected Mistic's motion on the microsecond-millisecond time scale.
      Halothane shifted the equilibrium of chemical exchange in some residues and made
      the exchange faster or slower in comparison to the original state in the absence
      of halothane. The motion on the microsecond-millisecond time scale in several
      residues disappeared in response to the addition of halothane. Most of the
      residues experiencing halothane-induced dynamics changes also exhibited profound
      halothane-induced changes in chemical shift, suggesting that dynamics
      modification of these residues might result from their direct interaction with
      halothane molecules. Allosteric modulation by halothane also contributed to
      dynamics changes, as reflected in residues I52 and Y82 where halothane
      introduction brought about dynamics changes but not chemical shift changes. The
      study suggests that inhaled general anesthetics could act on proteins via
      altering protein motion on the microsecond-millisecond time scale, especially
      motion in the flexible loops that link different alpha helices. The validation of
      anesthetic effect on protein dynamics that are potentially correlated with
      protein functions is a critical step in unraveling the mechanisms of anesthetic
      action on proteins.

PMID- 18821789
TI  - Ultrafast N-H vibrational dynamics of cyclic doubly hydrogen-bonded homo- and
      heterodimers.
AB  - Hydrogen-bonded interfaces are essential structural elements in biology.
      Furthermore, they can mediate electron transport by coupling the electron to
      proton transfer within the interface. The specific hydrogen-bonding configuration
      and strength have a large impact on the proton transfer, which exchanges the
      hydrogen-bonded donor and acceptor species (i.e., NH...O --> N...HO). Modulations
      of the hydrogen-bonding environment, such as the hydrogen-bond stretch and twist
      modes, affect the proton-transfer dynamics. Here, we present transient grating
      and echo peak shift measurements of the NH stretch vibrations of four doubly
      hydrogen-bonded cyclic dimers in their electronic ground state. The equilibrium
      vibrational dynamics exhibit strong coherent modulations that we attribute to
      coupling of the high-frequency NH vibration to the low-frequency interdimer
      stretch and twist modes and not to interference between multiple Fermi resonances
      that dominate the substructure of the linear spectra.

PMID- 18821790
TI  - The effect of the incident collision energy on the porosity of vapor-deposited
      amorphous solid water films.
AB  - Molecular beam techniques are used to grow water films on Pt(111) with various
      incident angles and collision energies from 5 to 205 kJ/mol. The effect of the
      incident angle and collision energy on the porosity and surface area of the vapor
      deposited water films was studied using nitrogen physisorption and infrared
      spectroscopy. At low incident energy (5 kJ/mol), the infrared spectra, which
      provide a direct measure of the surface area, show that the surface area
      increases with incident angle and levels off at angles > 65 degrees . This is in
      contrast to the nitrogen uptake data, which display a maximum near 65 degrees
      because of the decrease in nitrogen condensation in the larger pores that develop
      at high incident angles. Both techniques show that the morphology of vapor
      deposited water films depends strongly on the incident kinetic energy. These
      observations are consistent with a ballistic deposition shadowing model used to
      describe the growth of highly porous materials at glancing angle. The dependence
      of film morphology on incident energy may have important implications for the
      growth of porous materials via glancing angle deposition and for the structure of
      interstellar ices.

PMID- 18821791
TI  - Calculation of absolute ligand binding free energy to a ribosome-targeting
      protein as a function of solvent model.
AB  - A comparative analysis is provided of the effect of different solvent models on
      the calculation of a potential of mean force (PMF) for determining the absolute
      binding affinity of the small molecule inhibitor pteroic acid bound to ricin
      toxin A-chain (RTA). Solvent models include the distance-dependent dielectric
      constant, several different generalized Born (GB) approximations, and a hybrid
      explicit/GB-based implicit solvent model. We found that the simpler approximation
      of dielectric screening and a GB model, with Born radii fitted to a switching
      window dielectric-boundary surface Poisson solvent model, severely overpredicted
      the binding affinity as compared to the experimental value, estimated to range
      from -4.4 to -6.0 kcal/mol. In contrast, GB models that are parametrized to fit
      the Lee-Richards molecular surface performed much better, predicting binding free
      energy within 1-3 kcal/mol of experimental estimates. However, the predicted free
      energy profiles of these GB models displayed alternative binding modes not
      observed in the crystal structure. Finally, the most rigorous and computationally
      costly approach in this work, which used a hybrid explicit/implicit solvent
      model, correctly determined a binding funnel in the PMF near the crystallographic
      bound state and predicted an absolute binding affinity that was 2 kcal/mol more
      favorable than the estimated experimental binding affinity.

PMID- 18821792
TI  - Ultrafast infrared spectroscopy of riboflavin: dynamics, electronic structure,
      and vibrational mode analysis.
AB  - Femtosecond time-resolved infrared spectroscopy was used to study the vibrational
      response of riboflavin in DMSO to photoexcitation at 387 nm. Vibrational cooling
      in the excited electronic state is observed and characterized by a time constant
      of 4.0 +/- 0.1 ps. Its characteristic pattern of negative and positive IR
      difference signals allows the identification and determination of excited-state
      vibrational frequencies of riboflavin in the spectral region between 1100 and
      1740 cm (-1). Density functional theory (B3LYP), Hartree-Fock (HF) and
      configuration interaction singles (CIS) methods were employed to calculate the
      vibrational spectra of the electronic ground state and the first singlet excited
      pipi* state as well as respective electronic energies, structural parameters,
      electronic dipole moments and intrinsic force constants. The harmonic frequencies
      of the S 1 excited state calculated by the CIS method are in satisfactory
      agreement with the observed band positions. There is a clear correspondence
      between computed ground- and excited-state vibrations. Major changes upon
      photoexcitation include the loss of the double bond between the C4a and N5 atoms,
      reflected in a downshift of related vibrations in the spectral region from 1450
      to 1720 cm (-1). Furthermore, the vibrational analysis reveals intra- and
      intermolecular hydrogen bonding of the riboflavin chromophore.

PMID- 18821793
TI  - Attractions, water structure, and thermodynamics of hydrophobic polymer collapse.
AB  - We explore the prospects of a perturbation approach for predicting how weak
      attractive interactions affect collapse thermodynamics of hydrophobic polymers in
      water. Specifically, using molecular dynamics simulations of model polymers in
      explicit water, we show that the hydration structure is sensitive to the strength
      of the van der Waals attractions but that the hydration contribution to the
      potential of mean force for collapse is not. We discuss how perturbation theory
      ideas developed for small spherical apolar solutes need to be modified in order
      to account for the effect of attractions on the conformational equilibria of
      polymers.

PMID- 18821794
TI  - Surface characterization and biocompatibility of restorative resin containing
      nanoparticles.
AB  - Composite resins that are used to restore hard tissues have several drawbacks
      including the accumulation of biofilm on teeth and restorations. Recently,
      quaternary ammonium poly(ethylene imine) (QA-PEI) nanoparticles were developed
      for additional antibacterial activity of restorative composite resins. QA-PEI
      nanoparticles were synthesized from cross-linked poly(ethylene imine) that was N
      alkylated with octyl halide, followed by quaternary methylation with methyl
      iodide. QA-PEI particles that were embedded in restorative composite resin at 1%
      w/w resulted in the complete growth inhibition of Streptococcus mutans. Moreover,
      the antibacterial activity was retained for at least 3 months. The active
      substances on the surface of the restorative composite resin that were
      incorporated with QA-PEI particles were detected by X-ray photoelectron
      spectroscopy (XPS) and confocal microscopy measurements. The in vitro
      cytotoxicity tests showed a similar effect on the viability of the cell line that
      was tested with composites including modified and unmodified dental composite
      resins. In vivo toxicity studies, which were assessed on Wistar rats by the
      implantation of modified composite specimens, revealed no inflammation response 1
      week after the implantation of restorative composite resin that was embedded with
      up to 2% w/w QA-PEI.

PMID- 18821795
TI  - DNA nanotubes as combinatorial vehicles for cellular delivery.
AB  - This work explores using self-assembled DNA nanostructures as carriers for drug
      delivery. We have recently developed an organic nanotube system that is assembled
      from a single component: a 52-base-long DNA single strand. In this work,
      functional agents (folate as a cancer cell target agent and Cy3 as a fluorescence
      imaging agent) are conjugated with the DNA strands; the conjugates self-assemble
      into micrometers-long nanotubes (NTs). The conjugated DNA-NTs can be effectively
      taken by cancer cells as demonstrated by fluorescence imaging and fluorescence
      activated cell sorting. No obvious toxicity has been observed under current
      experimental conditions.

PMID- 18821796
TI  - Double-globular structure of porcine stomach mucin: a small-angle X-ray
      scattering study.
AB  - We present evidence from small-angle X-ray scattering synchrotron experiments
      that porcine stomach mucin (MUC6) contains a double-globular comb structure.
      Analysis of the amino acid sequence of the peptide comb backbone indicates that
      the globular structure is determined by both the charge and hydrophobicity of the
      amino acids and the placement of the short hydrophilic carbohydrate side chains
      (approximately 2.5 nm). The double-globular structure is, thus, due to a block
      copolymer type hydrophobic polyampholyte charge instability in contrast to the
      random copolymer instabilities observed previously with synthetic
      polyelectrolytes (particularly polystyrene sulfonates). Careful filtering was
      required to exclude multimonomer aggregates from the X-ray measurements. A double
      Guinier analysis ( R g approximately 26 nm) and a double power law fit are
      consistent with two globules per chain in low salt conditions. The average radius
      of the globules is approximately 10 nm in salt- free condition (double Guinier
      fit) and the average distance of intrachain separation of the globules is 48 nm.
      The addition of salt causes a significant decrease in the radius of gyration (14
      nm 100 mM NaCl) of the chains and is attributed to the contraction of the
      glycosylated peptide spacer between the two globules (the globular size continues
      to be approximately 10 nm and the globule separation is then 18 nm). Without
      salt, the scaling of the semidilute mesh size (xi) as a function of the mucin
      concentration (c) is xi approximately c (-0.45)compared with xi approximately c (
      0.28) in high salt conditions, highlighting the globular nature of the chains. In
      contrast, hydrophilic flexible polyelectrolytes have a stronger concentration
      dependence of xi when excess salt is added.

PMID- 18821797
TI  - Vesicles from peptidic side-chain polymers synthesized by atom transfer radical
      polymerization.
AB  - Block copolymers can adopt a wide range of morphologies in dilute aqueous
      solution. There is a significant amount of interest in the use of block copolymer
      vesicles for a number of applications. We show that a series of oligo(valine) and
      oligo(phenylalanine) peptides coupled to a methacrylic group can be prepared by
      conventional peptide coupling techniques. These can be successfully polymerized
      by atom transfer radical polymerization (ATRP) in hexafluoroisopropanol (HFIP)
      giving access to poly(ethylene oxide)- b-poly(side-chain peptides). Many of these
      polymers self-assemble to form vesicles using an organic to aqueous solvent
      exchange. One example with a divaline hydrophobic block gives a mixture of
      toroids and vesicles. Circular dichroism demonstrates that secondary structuring
      is observed in the hydrophobic region of the vesicle walls for the valine side
      chain containing polymers.

PMID- 18821798
TI  - Clerodane diterpenoids with NGF-potentiating activity from Ptychopetalum
      olacoides.
AB  - Four new clerodane-type diterpenoids, ptychonolide (1), 20-O-methylptychonal
      acetal (2), and an equilibrium mixture of ptychonal hemiacetal (3) and ptychonal
      (4), were isolated from the MeOH extract of the bark of a Brazilian plant,
      Ptychopetalum olacoides. The structure of 1 was elucidated as a clerodane-type
      diterpenoid on the basis of spectroscopic data, whereas 2 was assigned to an
      acetal derivative of 1. Compounds 3 and 4 existed as an equilibrium mixture. A
      mixture of compounds 3 and 4 was found to exhibit neurite outgrowth-promoting
      activities on NGF-mediated PC12 cells at concentrations ranging from 0.1 to 10.0
      microM.

PMID- 18821800
TI  - Zwitterionic phosphonium sulfonates as easily phase-separable ion-tagged Wittig
      reagents.
AB  - Zwitterionic phosphonium sulfonates 3, conveniently derived from TPPMS (1), can
      be used as Wittig reagents in solution. The excess reagents and byproduct TPPMSO
      (6) can be easily separated from the product alkenes by simple precipitation with
      a less polar solvent. The alkenes thus obtained were often sufficiently pure
      without chromatographic purification. A one-pot protocol for the synthesis of
      alpha,beta-unsaturated esters has been developed and appears to be convenient.

PMID- 18821801
TI  - Synthesis and biological evaluation of a phosphonate analog of the natural acetyl
      cholinesterase inhibitor cyclophostin.
AB  - Two diastereomers of a phosphonate analog 6 of the AChE inhibitor cyclophostin
      were synthesized. The substitution reaction of phosphono allylic carbonate 10a
      with methyl acetoacetate gave the vinyl phosphonate 9a. Attempted
      hydrogenation/debenzylation gave an unexpected enolether lactone. Alternatively,
      selective hydrogenation, demethylation, cyclization and debenzylation gave the
      phosphonate analog of cyclophostin as a separable mixture of diastereomers 6. The
      trans phosphonate isomer was more active than the cis isomer against AChE from
      two sources.

PMID- 18821802
TI  - N-carbamate protected alpha-amidoalkyl-p-tolylsulfones: convenient substrates in
      the aza-Morita-Baylis-Hillman reaction.
AB  - An efficient and practical one-pot approach to aza-Morita-Baylis-Hillman adducts
      has been developed. The reaction occurs between N-Boc or N-Cbz imines, generated
      in situ from stable and easy to handle N-Boc or N-Cbz protected alpha-amidoalkyl
      p-tolylsulfones, and electron-deficient alkenes in the presence of DABCO. The
      presented procedure eliminates the use of the relatively unstable N-carbamate
      imines prior to the coupling reaction. The reaction is limited to alpha
      amidosulfones derived from aromatic and heteroaromatic aldehydes.

PMID- 18821803
TI  - Povarov reactions involving 3-aminocoumarins: synthesis of 1,2,3,4
      tetrahydropyrido[2,3-c]coumarins and pyrido[2,3-c]coumarins.
AB  - Condensation of 3-aminocoumarin (5) with 4-nitrobenzaldehyde (8) afforded a 2
      azadiene (9), which reacted with various electron-rich alkenes (10 examples) in
      the presence of Yb(OTf)3 to afford 1,2,3,4-tetrahydropyrido[2,3-c]coumarins.
      Yields were generally good, but the diastereomeric ratios were highly variable.
      The products arose through a formal [4 + 2] cycloaddition (inverse electron
      demand Diels-Alder reaction) followed by tautomerization. As such, these are
      examples of the Povarov reaction. A range of 1,2,3,4-tetrahydropyrido[2,3
      c]coumarins was then synthesized using a three-component version of this
      reaction, which involves in situ formation of the 2-azadiene component. Some of
      these products were converted into the corresponding pyrido[2,3-c]coumarins upon
      treatment with various oxidants, the most effective of which proved to be nitrous
      gases.

PMID- 18821804
TI  - Oxidative aromatization of olefins with dioxygen catalyzed by palladium
      trifluoroacetate.
AB  - Molecular oxygen can replace sacrificial olefins as the hydrogen acceptor in the
      palladium trifluoroacetate catalyzed dehydrogenation of cyclohexene and related
      cyclic olefins into aromatics. One of the major drawbacks of the homogeneous
      system is the tendency of the palladium trifluoroacetate to precipitate as
      palladium(0) at elevated temperatures. The use of better ligands affords
      catalysts that can operate at higher temperatures, although they are less
      reactive than palladium trifluoroacetate.

PMID- 18821805
TI  - Hydride affinities of cumulated, isolated, and conjugated dienes in acetonitrile.
AB  - The hydride affinities (defined as the enthalpy changes in this work) of 15
      polarized dienes [five phenyl sulfone substituted allenes (1a), the corresponding
      five isolated dienes (1b), and the corresponding five conjugated dienes (1c)] in
      acetonitrile solution were determined by titration calorimetry for the first
      time. The results display that the hydride affinity scales of the 15 dienes in
      acetonitrile range from -71.6 to -73.9 kcal/mol for 1a, from -46.2 to -49.7
      kcal/mol for 1b, and from -45.0 to -46.5 kcal/mol for 1c, which indicates that
      the hydride-obtaining abilities of the cumulated dienes (1a) are not only much
      larger than those of the corresponding conjugated dienes (1c) but also much
      larger than those of the corresponding isolated dienes (1b). The hydrogen
      affinities of the 15 dienes as well as the hydrogen affinities and the proton
      affinities of the radical anions of the dienes (1(-*)) in acetonitrile were also
      evaluated by using relative thermodynamic cycles according to Hess's law. The
      results show that (i) the hydrogen affinities of the neutral dienes 1 cover a
      range from -44.5 to -45.6 kcal/mol for 1a, from -20.4 to -21.4 kcal/mol for 1b,
      and from -17.3 to -18.5 kcal/mol for 1c; (ii) the hydrogen affinities of the
      radical anions of the dienes (1(-*)) in acetonitrile cover a range from -40.6 to 
      47.2 kcal/mol for 1a(-*), from -21.6 to -29.6 kcal/mol for 1b(-*), and from -10.0
      to -15.4 kcal/mol for 1c(-*); (iii) the proton affinities of the 15 1a(-*) in
      acetonitrile cover a range from -97.0 to -100.6 kcal/mol for 1a(-*), from -77.8
      to -83.4 kcal/mol for 1b(-*), and from -66.2 to -68.9 kcal/mol for 1c(-*). The
      main reasons for the great difference between the cumulated dienes and the
      corresponding isolated and conjugated dienes in the hydride affinity, hydrogen
      affinity, and proton affinity have been examined. It is evident that these
      experimental results should be quite valuable to facilitate the elucidation of
      the origins of the especially high chemical potencies of the allenes, the choice
      of suitable hydride reducing agents to reduce the dienes, and the analyses on the
      reduction mechanisms.

PMID- 18821806
TI  - Solid-phase synthesis of 4-methylcarboxy-1,4-benzodiazepine-2,5-diones.
AB  - A solid-phase synthesis of 1,4-benzodiazepinone-2,5-diones is described. This new
      route can afford benzodiazepinone bearing a N-urethane-protected amine and a
      carboxylic acid function. This kind of building block is valuable as a dipeptide
      mimic or beta-turn mimetic, and it can be introduced in place of any amino acid
      in peptide synthesis. Using an "analytical probe" strategy, we optimized the
      synthesis of a model compound on SynPhase Lanterns. Therefore, the efficiency of
      several linkers was investigated.

PMID- 18821807
TI  - Molecular aspects of biomineralization of the echinoderm endoskeleton.

PMID- 18821808
TI  - Preface: Overview of the forum on functional inorganic materials.

PMID- 18821809
TI  - Recent progress in oxide thermoelectric materials: p-type Ca3Co4O9 and n-type
      SrTiO3(-).
AB  - Thermoelectric energy conversion technology to convert waste heat into
      electricity has received much attention. In addition, metal oxides have recently
      been considered as thermoelectric power generation materials that can operate at
      high temperatures on the basis of their potential advantages over heavy metallic
      alloys in chemical and thermal robustness. We have fabricated high-quality
      epitaxial films composed of oxide thermoelectric materials that are suitable for
      clarifying the intrinsic "real" properties. This review focuses on the
      thermoelectric properties of two representative oxide epitaxial films, p-type Ca
      3Co 4O 9 and n-type SrTiO 3, which exhibit the best thermoelectric figures of
      merit, ZT (= S (2)sigma Tkappa (-1), S = Seebeck coefficient, sigma = electrical
      conductivity, kappa = thermal conductivity, and T = absolute temperature) among
      oxide thermoelectric materials reported to date. In addition, we introduce the
      recently discovered giant S of two-dimensional electrons confined within a unit
      cell layer thickness ( approximately 0.4 nm) of SrTiO 3.

PMID- 18821810
TI  - Optical properties of cation-substituted zinc oxide.
AB  - Zinc oxide (ZnO)-based optoelectronics has emerged as a frontier area in
      semiconductor research in recent years. In the design of ZnO-based optoelectronic
      devices, cation-substituted ZnO serves as essential components for the desired
      device functions. Band-gap engineering by cation substitution enables the facile
      preparation of barrier layers and quantum wells in device structures. Wurtzite
      solid solutions Zn 1- x Mg x O, Zn 1- x Cd x O, and Zn 1- x Be x O have been
      reported as examples where band gaps are gradually modulated as functions of x.
      In this contribution, we present an overview of composition-dependent band-gap
      variations of Zn 1- x M x O solid solutions. In addition, we describe the optical
      properties and microstructural evolution in polycrystalline Zn 1- x Mg x O (0
      <or= x <or= 0.15). It is proposed that chemical strain associated with cation
      substitution has an impact on the band-gap magnitude, crystallite morphology, and
      optical defects.

PMID- 18821811
TI  - Isolation of two-dimensional 2:1 cation-ordered perovskite units by anion vacancy
      ordering in Ba6Na2Nb2P2O17.
AB  - A new six-layer perovskite-related structure Ba 6Na 2Nb 2M 2O 17 (M = P, V),
      which consists of cubic (c) BaO 3 layers and oxygen-deficient pseudocubic (c')
      BaO 2 layers stacked in the sequence c'ccccc, is presented. In Ba 6Na 2Nb 2M 2O
      17, two-dimensional slabs of the well-known 2:1 octahedral cation-ordered
      perovskite motif are isolated between layers of tetrahedral units formed by anion
      vacancy ordering: two consecutive NbO 6 octahedral layers are sandwiched by two
      single NaO 6 octahedral layers, which, in turn, connect with two isolated MO 4
      tetrahedral layers. Both oxides are derived from the 2:1 ordered perovskite
      structure (e.g., Ba 3ZnTa 2O 9) by ordered removal of O atoms in every sixth BaO
      3 layer. Both materials exhibit a relative permittivity of approximately 20-23, Q
      x f 0 values of approximately 7800-10600 GHz, and negative temperature
      coefficients of the resonant frequency of approximately -23 to -7 ppm/ degrees C.

PMID- 18821812
TI  - Role of temperature and time in the formation of infinite -M-O-M- linkages and
      isolated clusters in MOFs: a few illustrative examples.
AB  - The role of temperature and time of reaction in the formation of metal-organic
      frameworks (MOFs) has been studied in two systems of compounds, manganese
      oxybis(benzoate) and manganese trimellitates, and the results compared and
      contrasted with other similar studies in the literature. The investigation
      reveals the formation of six different phases in oxybis(benzoate) and three
      phases in trimellitate systems. The low-temperature phases in both systems of
      compounds possess Mn 4 cluster units linked by the carboxylate ligands, while the
      high-temperature phase, irrespective of the duration of the reaction, has a three
      dimensional structure with -Mn-O-Mn- linkages with brucite-related layers
      pillared by oxybis(benzoate) and Kagome-related layers pillared by trimellitate
      ligands. In all of the preparation, the reactions appear to have thermodynamic
      control as a function of the temperature. The isolation of low-dimensional
      structures in manganese oxybis(benzoate) at moderate time and temperature
      indicates possible kinetic control. The formation of reactive low-dimensional
      phases has been rationalized by considering the local charge distribution around
      the Mn site and also invoking a possible dissolution-recrystalization mechanism.

PMID- 18821813
TI  - Ag4V2O6F2 (SVOF): a high silver density phase and potential new cathode material
      for implantable cardioverter defibrillators.
AB  - The electrochemical reactivity of the cathode material Ag 4V 2O 6F 2 (SVOF)
      versus lithium, with a particular emphasis on the lithium insertion mechanism,
      was studied by means of the complementary techniques in situ X-ray diffraction,
      electron paramagnetic resonance, and high-resolution transmisssion electron
      microscopy. This study confirms the initial reports of a high capacity for SVOF
      of 148 mAh/g above 3 V and that the reduction of silver above 3 V (vs Li (+)/Li
      (0)) leads to a loss of SVOF crystallinity until it becomes completely amorphous
      between the third and fourth lithiums inserted. Next, vanadium is reduced between
      2.5 and 1.5 V (vs Li (+)/Li (0)) for the fifth and sixth lithiums inserted. In
      addition, the polarization within the cathode is significantly lower for the
      vanadium reduction than for the silver reduction. The silver metal morphologies
      consisted of nanoparticles ( approximately 5 nm diameter) and dendrites and were
      both seen in samples of lithiated SVOF.

PMID- 18821814
TI  - Structures, physical properties, and chemistry of layered oxychalcogenides and
      oxypnictides.
AB  - A series of layered oxychalcogenide and oxypnictide solids is described that
      contain oxide layers separated by distinct layers, which contain the softer
      chalcogenide (S, Se, Te) or pnictide (P, As, Sb, Bi) anions. The relationships
      between the crystal structures adopted by these compounds are described, and the
      physical and chemical properties of these materials are related to the structures
      and the properties of the elements. The properties exhibited by the
      oxychalcogenide materials include semiconductor properties, for example, in
      LaOCuCh (Ch = chalcogenide) and derivatives, unusual magnetic properties
      exhibited by the class Sr 2MO 2Cu 2-deltaS 2 (M = Mn, Co, Ni), and redox
      properties exhibited by the materials Sr 2MnO 2Cu 2 m-0.5 S m+1 ( m = 1-3) and Sr
      4Mn 3O 7.5Cu 2Ch 2 (Ch = S, Se). Recent results in the oxychalcogenide area are
      reviewed, and some new results on the intriguing series of compounds Sr 2MO 2Cu 2
      deltaS 2 (M = Mn, Co, Ni) are reported. Oxypnictides have received less recent
      attention, but this is changing: a new frenzy of research is underway following
      the discovery of high-temperature superconductivity (>40 K) in derivatives of the
      layered oxyarsenide LaOFeAs. The early results in this exciting new area will be
      reviewed.

PMID- 18821815
TI  - Status of trivalent copper and charge-transfer excitons in high-TC cuprates.
AB  - A chemical bonding approach based on tight-binding cluster and band calculations,
      taking into account on-site Coulomb repulsion (Hubbard U parameter) to
      differentiate doubly and singly occupied states, was applied to high- T C
      superconducting cuprates and related compounds. This work provides rational
      insight and explanations for issues such as (i) the actual oxidation number Cu
      (I+) for formally trivalent copper in oxides such as La 2Li 1/2Cu 1/2O 4, (ii)
      the dominant oxygen character of the doping holes in (CuO 2) ( n- ) planes, (iii)
      the Mott-Hubbard character of the insulator-to-metal transition triggered by hole
      doping, leading to an oxygen-to-copper charge transfer of avalanche type, (iv)
      the occurrence of an excitonic phase with anisotropic Frenkel-type excitons, (v)
      the role of Coulomb interactions between excitons and between doping holes and
      their exciton surroundings, and (vi) the on-time pairing of doping holes by means
      of an "excitonic glue".

PMID- 18821816
TI  - Structures and properties of functional metal selenites and tellurites.
AB  - Metal selenites and tellurites are a class of very important compounds. In this
      paper, the structures and properties of metal selenites or tellurites combining
      with transition-metal (TM) ions with the d (0) electronic configuration or
      tetrahedral MO 4 building blocks of post-transition main-group elements were
      reviewed. Most compounds in the alkali or alkaline-earth-d (0) TM-Se (IV) (or Te
      (IV))-O systems exhibit extended anionic architectures composed of distorted
      octahedra of (d (0)) TM cations and tellurite or selenite groups. The distortion
      of the octahedron is always away from the lone-pair cation, and some of them
      exhibit excellent second-order nonlinear optical properties due to the adductive
      effects of two types of bond polarizations. Because of the high coordination
      number of Ln (III) ions, most of compounds in the Ln-d (0) TM-Se (IV) (or Te
      (IV))-O systems are not second-harmonic-generation active; however, they are able
      to emit strong luminescence in the visible or near-IR region; also in most cases,
      the d (0) TM cations are in tetrahedral geometry and are well separated from
      selenite or tellurite groups. It is also interesting to note that the selenite
      group is normally "isolated", whereas the TeO x ( x = 3-5) can be polymerized
      into a variety of discrete polynuclear anionic clusters or extended architectures
      via Te-O-Te bridges.

PMID- 18821817
TI  - Polar hexagonal tungsten bronze-type oxides: KNbW2O9, RbNbW2O9, and KTaW2O9.
AB  - The synthesis, crystal structures, second-harmonic generation (SHG),
      piezoelectric, pyroelectric, and ferroelectric properties of three polar
      noncentrosymmetric (NCS) hexagonal tungsten bronze-type oxides are reported. The
      materials KNbW 2O 9, RbNbW 2O 9, and KTaW 2O 9 were synthesized by standard solid
      state techniques and structurally characterized by laboratory powder X-ray
      diffraction. The compounds are isostructural, crystallizing in the polar NCS
      space group Cmm2. The materials exhibit a corner-shared MO 6 (M = Nb (5+)/W (6+)
      or Ta (5+)/W (6+)) octahedral framework, with K (+) or Rb (+) occupying the
      "hexagonal" tunnels. The d (0) transition metals, Nb (5+), Ta (5+), and W (6+),
      are displaced from the center of their oxide octahedra attributable to second
      order Jahn-Teller effects. SHG measurements using 1064 nm radiation revealed
      frequency-doubling efficiencies ranging from 180 to 220 x alpha-SiO 2. Converse
      piezoelectric measurements resulted in d 33 values ranging from 10 to 41 pm V (
      1). The total pyroelectric coefficient, p, at 50 degrees C ranged from -6.5 to 
      34.5 muC K (-1) m (-2). The reported materials are also ferroelectric, as
      demonstrated by hysteresis loops (polarization vs electric field). Spontaneous
      polarization values, P s, ranging from 2.1 to 8.4 muC cm (-2) were measured. The
      magnitudes of the SHG efficiency, piezoelectric response, pyroelectric
      coefficient, and ferroelectric polarization are strongly dependent on the out-of
      center distortion of the d (0) transition metals. Structure-property
      relationships are discussed and explored. Crystal data: KNbW 2O 9, orthorhombic,
      space group Cmm2 (No. 35), a = 21.9554(2) A, b = 12.60725(15) A, c = 3.87748(3)
      A, V = 1073.273(13) A (3), and Z = 6; RbNbW 2O 9, orthorhombic, space group Cmm2
      (No. 35), a = 22.00985(12) A, b = 12.66916(7) A, c = 3.8989(2) A, V =
      1086.182(10) A (3), and Z = 6; KTaW 2O 9, orthorhombic, space group Cmm2 (No.
      35), a = 22.0025(2) A, b = 12.68532(14) A, c = 3.84456(4) A, V = 1073.05(2) A
      (3), and Z = 6.

PMID- 18821818
TI  - Synthetic approaches for noncentrosymmetric molybdates.
AB  - The use of second-order Jahn-Teller active Mo (VI) centers and chiral organic
      amines is discussed as an approach to crystallographic noncentrosymmetry. Several
      series of reactions, conducted under mild hydrothermal conditions, were designed
      to probe important reaction variables. Correlations between reagent and solvent
      concentrations and the molybdate structure were investigated using composition
      space analysis, which allows for the isolation of specific reaction variables.
      The effects of amine structure variation were probed using multiple series of
      related amines, which consisted of either linear diamines or ethylenediamine
      derivatives. The addition of fluoride results in the loss of amine-based
      structural variations. Chiral organic amines were used to demonstrate the
      viability of using such components to control the three-dimensional symmetry in
      new materials. The synthesis, structure, and characterization of eight new
      organically templated polyoxomolybdates and polyoxofluoromolybdates are reported.

PMID- 18821819
TI  - Increasing the structural complexity of chromium(IV) oxides by high-pressure and
      high-temperature reactions of CrO2.
AB  - This work presents an overview of a series of increasingly complex oxides
      synthesized from CrO 2, under high-pressure and high-temperature conditions,
      having Cr (4+) in octahedral coordination. Although the emphasis is on the
      structure and microstructure of the compounds as obtained from X-ray diffraction
      and transmission electron microscopy and diffraction, attention is also given to
      their interesting electronic and magnetic properties. The study is complemented
      with an electron energy loss spectroscopic analysis of the different phases.
      These are the cubic perovskite SrCrO 3, the orthorhombic perovskite CaCrO 3, the
      solid solution Sr 1-xCa xCrO 3, the Ruddlesden-Popper-type Sr 3Cr 2O 7, the
      family CrSr 2RECu 2O 8 (RE = rare earth), a compositionally modulated perovskite
      "PbCrO 3", and the misfit layer oxide SrO 2[CrO 2] 1.85.

PMID- 18821820
TI  - Target-aimed synthesis of anion-deficient perovskites.
AB  - The brownmillerite-type A 2B 2O 5 structure is considered as a parent one, giving
      rise to different derivatives: layered double perovskites, A-site and anion
      vacancy-ordered perovskites, and the perovskite-like compounds with
      crystallographic shear planes. The structural relationships and synthesis
      pathways for these classes of materials are discussed with particular attention
      to the ordering at the A or B sublattices, anion vacancy ordering, and their
      mutual interaction.

PMID- 18821821
TI  - Transition-metal oxides with triangular lattices: generation of new magnetic and
      electronic properties.
AB  - The search for multifunctional materials as multiferroics to be applied in
      microelectronic or for new, chemically stable and nontoxic, thermoelectric
      materials to recover waste heat is showing a common interest in the oxides whose
      structures contain a triangular network of transition-metal cations. To
      illustrate this point, two ternary systems, Ba-Co-O and Ca-Co-O, have been
      chosen. It is shown that new phases with a complex triangular structure can be
      discovered, for instance, by introduction of Ga (3+) into the Ba-Co-O system to
      stabilize Ba 6Ga 2Co 11O 26 and Ba 2GaCo 8O 14, which both belong to a large
      family of compounds with formula [Ba(Co,Ga)O 3-delta] n [BaCo 8O 11]. In the
      latter, both sublattices contain triangular networks derived from the hexagonal
      perovskite and the spinel structure. Among the hexagonal perovskite, the Ca 3Co
      2O 6 crystals give clear evidence where the coupling of charges and spins is at
      the origin of a magnetocapacitance effect. In particular, the ferrimagnetic to
      ferromagnetic transition, with a one-third plateau on the M( H) curve
      characteristic of triangular magnetism, is accompanied by a peak in the
      dielectric constant. A second class of cobaltites is the focus of much interest.
      Their 2D structure, containing CoO 2 planes isostructural to a CdI 2 slice that
      are stacked in an incommensurate way with rock salt type layers, is referred to
      misfit cobaltite. The 2D triangular network of edge-shared CoO 6 octahedra is
      believed to be responsible for large values of the Seebeck coefficient and low
      electrical resistivity. A clear relationship between the
      structuresincommensurability ratiosand the electronic properties is evidenced,
      showing that the charge carrier concentration can be tuned via the control of the
      ionic radius of the cations in the separating layers.

PMID- 18821822
TI  - A-site-ordered perovskites with intriguing physical properties.
AB  - Recent findings on intriguing physical properties of new A-site-ordered
      perovskite structure oxides are reviewed. High-pressure and high-temperature
      conditions stabilize the square-coordinated Jahn-Teller Cu (2+) ions in the
      original 12-fold-coordinated positions of the perovskite structure. The special
      ordered arrangement of the square-coordinated A'O 4 units that align
      perpendicularly to each other sets a characteristic structural framework, and the
      presence of Cu (2+) ions at the A' site and A'-B interactions play crucial roles
      for the diverse and intriguing physical properties.

PMID- 18821823
TI  - Comparative phylogenetic histories of two louse genera found on Catharus thrushes
      and other birds.
AB  - The louse genera Brueelia (Ischnocera) and Myrsidea (Amblycera) are broadly
      codistributed on songbirds (Passeriformes), but differ in a variety of life
      history characteristics. We used mitochondrial and nuclear DNA sequences to
      assess levels of genetic divergence and reconstruct phylogenies of these 2
      genera, focusing especially on Catharus thrushes in North America. We then
      qualitatively compared the phylogenies and levels of divergence within these 2
      genera of codistributed parasites. Neither Brueelia nor Myrsidea appears to
      cospeciate with Catharus thrushes or passerine birds in general. The Myrsidea
      phylogeny exhibits significant levels of biogeographic structure, whereas the
      Brueelia phylogeny does not. Myrsidea and Brueelia also differ in their levels of
      intra-generic genetic divergence, with Myrsidea showing higher levels of genetic
      divergence and host specificity than Brueelia. Our genetic data support
      traditional morphology-based taxonomy in several instances in which the same
      species of Brueelia has been reported on multiple host taxa, e.g., all migrant
      Catharus spp. carry B. antiqua, with little haplotype divergence. Myrsidea found
      on each Catharus sp. are in general genetically distinct, except for M. incerta,
      which parasitizes both Catharus ustulatus and Catharus minimus. The strong
      biogeographic signal in the Myrsidea phylogeny and higher relative levels of host
      specificity of Myrsidea spp. suggest that infrequent host-switching, followed by
      speciation, is shaping the evolutionary history of this group. In contrast, the
      relatively lower host specificity of Brueelia spp. suggests that host-switching,
      combined with more frequent ongoing dispersal, has been more important in the
      evolutionary history of Brueelia.

PMID- 18821824
TI  - Infection of primary canine duodenal epithelial cell cultures with Neospora
      caninum.
AB  - According to current knowledge, sexual development of the apicomplexan parasite
      Neospora caninum takes place in the canine intestine. However, to date there is
      no information on the interaction between the parasite and the canine intestinal
      epithelium, and, next to the clinical and in vivo research tools, an in vitro
      model comprised of canine intestinal cells infected with N. caninum would be very
      helpful for investigations at the cellular level. Following the isolation of
      cells of neonatal canine duodenum and growth of cell cultures to monolayers for 5
      6 days, canine intestinal epithelial cells were exposed to cell culture-derived
      N. caninum tachyzoites and bradyzoites. The host cells remained viable during in
      vitro culture for an average of 2 wk. During this time span, N. caninum was found
      to readily adhere to any surface area of these cells, but infection took mostly
      place at sites where microvilli-like structures were missing, e.g., at the cell
      periphery, with tachyzoites exhibiting at least 3-4 times increased invasive
      capacities compared to bradyzoites. Once intracellular, parasites resided within
      a parasitophorous vacuole, moved toward the vicinity of the nucleus and the more
      distal portion of the epithelial cells, and proliferated to form vacuoles of not
      more than 2-4 parasites, which were surrounded by numerous mitochondria.
      Immunofluorescence staining and TEM of infected cells showed that the expression
      of cytokeratins and the structural integrity of desmosomes and tight junctions
      were not notably altered during infection. Furthermore, no changes could be
      detected in the alkaline phosphatase activities in cell culture supernatants of
      infected and noninfected cells. Canine duodenal epithelial cell cultures
      represent a useful tool for future studies on the characteristics of the
      intestinal phases of N. caninum infection.

PMID- 18821825
TI  - Acceptance of the 2008 Henry Baldwin Ward Medal: balancing the tripod.

PMID- 18821826
TI  - Megalencephalic leukoencephalopathy with subcortical cysts: a third confirmed
      case with literature review.
AB  - Megalencephalic leukoencephalopathy with subcortical cysts (MLC) causes early
      onset, slowly progressive central nervous system white matter disease,
      macrocephaly, and later cognitive and motor decline. We describe brain structure
      in a patient with MLC and proven MLC1 mutations. A male, normal at birth, had
      macrocephaly at 6 months followed by developmental delay. Magnetic resonance
      imaging showed extensive signal abnormality in cerebral white matter and
      subcortical progressive cystic changes in the bilateral temporal and right
      frontal areas. Biopsy of frontal gyrus at age 15 months showed normal gray
      matter. The subcortical white matter was pale due to prominent fine uniform 2- to
      4-mu-thick vacuoles with a few interspersed myelinated axons and rare microglia.
      The vacuoles had a single-, double-, or, rarely, triple-unit membrane (resembling
      myelin) and contained occasional organelles but no intermediate filaments. Both
      normal myelinated and thinly myelinated axons were observed. The outer and
      occasionally the inner layers of myelin surrounding intact axons formed blebs
      that may represent a source for vacuoles. Genetic analysis identified 2
      heterozygous mutations of intron 3 (c.322-1 G>A) and intron 7 (c.597+1G>A), the
      1st leading to deletion of amino acids 60 to 89 and the 2nd to deletion of amino
      acids 194 to 199. Fine uniform vacuolation of white matter with wide separation
      of myelinated axons is the hallmark of MLC in early childhood.

PMID- 18821827
TI  - Human embryonic and mesenchymal stem cells express different nuclear proteomes.
AB  - Human embryonic stem cells (hESCs) are characterized by their immortality and
      pluripotency. Human mesenchymal stem cells (hMSC), on the other hand, have
      limited self-renewal and differentiation capabilities. The underlying molecular
      differences that account for this characteristic self-renewal and plasticity are,
      however, poorly understood. This study reports a nuclear proteomic analysis of
      human embryonic and bone marrow-derived mesenchymal stem cells. Our proteomic
      screen highlighted a 5-fold difference in the expression of Reptin52. We show,
      using two-dimensional difference gel electrophoresis (2-DIGE), western analysis,
      and quantitative reverse transcriptase polymerase chain reaction, that Reptin52
      is more abundantly expressed in hESC than hMSC. Moreover, we observed
      differential expression of Pontin52 and beta-catenin-proteins known to interact
      with Reptin52. This difference in the expression of Reptin52 and Pontin52 (known
      regulators of beta-catenin) further supports a role for Wnt signaling in stem
      cell self-renewal and proliferation.

PMID- 18821828
TI  - Sulcal and ventricular trajectories in stereotactic surgery.
AB  - OBJECT: The authors analyzed deep brain stimulation electrode trajectories on MR
      images to identify risks of cerebrovascular complications associated with the
      number of electrode insertions, traversal of a sulcus, and penetration of the
      ventricle. METHODS: Pre- and postoperative MR volumes were fused to determine the
      proximity of electrodes to a sulcus or ventricle and whether there were cortical,
      subcortical, or intraventricular complications. Complications were further
      classified as hemorrhagic or nonhemorrhagic and symptomatic or asymptomatic. The
      authors examined 258 electrode implantation for deep brain stimulation. There
      were 4 symptomatic events (1.6% incidence): 3 hemorrhagic and 1 nonhemorrhagic,
      all within the cortex. Asymptomatic events included cortical hemorrhage in 1
      patient, nonhemorrhagic cortical changes in 6, pallidal hemorrhage in 1, thalamic
      infarction in 1, and intraventricular hemorrhage (IVH) in 5 patients. RESULTS:
      Proximity to a sulcus was a significant risk factor for hemorrhagic and
      nonhemorrhagic cortical complications (p = 0.001). There was a complication rate
      of 10.1% within the trajectories penetrating or adjacent to a sulcus, and a 0.7%
      rate with trajectories clearly positioned within the gyrus. Asymptomatic IVH was
      observed in 5% of ventricular penetrations. A history of hypertension was a risk
      factor for cortical hemorrhage (p = 0.019), but not for cortical
      ischemic/edematous events (p = 0.605). The number of electrode penetrations did
      not differ between patients with and without complications (p = 0.868), and the
      sequence of electrode insertions was not a risk factor in bilateral surgeries.
      CONCLUSIONS: Symptomatic cortical complications occur when electrodes traverse
      close to a sulcus. Asymptomatic IVH occurs infrequently with ventricular
      penetration. Despite intraoperative efforts to avoid cortical sulci, a higher
      than expected incidence of electrode proximity to the sulci was identified on
      careful postoperative trajectory analysis. This finding emphasizes the importance
      of assiduously planning trajectories and reviewing cases with thorough MR
      analysis.

PMID- 18821829
TI  - Responsiveness of short-lasting unilateral neuralgiform headache with
      conjunctival injection and tearing to hypothalamic deep brain stimulation.
AB  - Short-lasting unilateral neuralgiform headache with conjunctival injection and
      tearing (SUNCT) is a severe primary headache disorder that is often refractory to
      medical therapy. Although the pathogenesis of this and other trigeminal autonomic
      cephalalgias is not completely understood, ipsilateral activation of the
      posterior and inferior hypothalamus has been identified on functional imaging
      studies during attacks. The authors report on a case of SUNCT syndrome
      successfully treated with hypothalamic deep brain stimulation and discuss the
      current literature.

PMID- 18821830
TI  - Accuracy of transcranial Doppler ultrasonography and single-photon emission
      computed tomography in the diagnosis of angiographically demonstrated cerebral
      vasospasm.
AB  - OBJECT: The goal of this study was to assess the accuracy of the routine clinical
      use of transcranial Doppler (TCD) ultrasonography and SPECT in predicting
      angiographically demonstrated vasospasm. METHODS: Following receipt of
      institutional review board approval, the authors reviewed the records of patients
      with subarachnoid hemorrhage who had been admitted between 2004 and 2005 and
      underwent TCD ultrasonography and SPECT evaluations within 24 hours of cerebral
      angiography. Patients were categorized based on the presence or absence of
      vasospasm and/or hypoperfusion in the anterior cerebral arteries (ACAs), middle
      cerebral arteries (MCAs), and basilar arteries (BAs) or posterior cerebral
      arteries (PCAs) according to each imaging modality. Logistic regression was used
      to estimate the odds ratio (OR) of an angiographically demonstrated vasospasm
      also detected on TCD ultrasonography and SPECT. RESULTS: One hundred fifty-two
      patients (101 women) with a mean age (+/- standard deviation) of 53 +/- 13 years
      were included in the study. In the ACA, the OR of a vasospasm on TCD
      ultrasonography was 27 (95% confidence interval [CI] 3-243) and on SPECT 0.97
      (95% CI 0.36-2.6); in the MCA, 17 (95% CI 5.4-55) and 2.0 (95% CI 0.71-5.5),
      respectively; in the BA, 4.4 (95% CI 0.72-27) and 5.6 (95% CI 0.89-36),
      respectively. There was no substantial change in the relative odds of a vasospasm
      when the findings on TCD ultrasonography and SPECT were considered jointly.
      CONCLUSIONS: Transcranial Doppler ultrasonography appears to be highly predictive
      of an angiographically demonstrated vasospasm in the MCA and ACA; however, its
      diagnostic accuracy was lower with regard to vasospasm in the BA. Single-photon
      emission computed tomography was not predictive of a vasospasm in any of the
      vascular territories assessed.

PMID- 18821831
TI  - The contralateral long thoracic nerve as a donor for upper brachial plexus
      neurotization procedures: cadaveric feasibility study.
AB  - OBJECT: Various donor nerves, including the ipsilateral long thoracic nerve
      (LTN), have been used for brachial plexus neurotization procedures. Neurotization
      to proximal branches of the brachial plexus using the contralateral long thoracic
      nerve (LTN) has, to the authors' knowledge, not been previously explored.
      METHODS: In an attempt to identify an additional nerve donor candidate for
      proximal brachial plexus neurotization, the authors dissected the LTN in 8 adult
      human cadavers. The nerve was transected at its distal termination and then
      passed deep to the clavicle and axillary neurovascular bundle. This passed
      segment of nerve was then tunneled subcutaneously and contralaterally across the
      neck to a supra- and infraclavicular exposure of the suprascapular and
      musculocutaneous nerves. Measurements were made of the length and diameter of the
      LTN. RESULTS: All specimens were found to have a LTN that could be brought to the
      aforementioned contralateral nerves. Neural connections remained tension free
      with left and right neck rotation of approximately 45 degrees . The mean length
      of the LTN was 22 cm with a range of 18-27 cm. The overall mean diameter of this
      nerve was 3.0 mm. No gross evidence of injury to surrounding neurovascular
      structures was identified in any specimen. CONCLUSIONS: Based on the results of
      this cadaveric study, the use of the contralateral LTN may be considered for
      neurotization of the proximal musculocutaneous and suprascapular nerves.

PMID- 18821832
TI  - Early brain tumor metastasis reduction following Gamma Knife surgery.
AB  - OBJECT: Unlike whole-brain radiation therapy, Gamma Knife surgery (GKS) is
      delivered in a single session for the treatment of brain metastases. The extent
      to which GKS can facilitate early tumor control was the focus of this study.
      METHODS: The authors reviewed 134 metastatic lesions in 82 patients treated with
      GKS at the University of Virginia who underwent follow-up MR imaging within 30
      days or less of GKS. For accurate volumetry only tumors measuring 0.5 cm3 or
      greater in volume were included. Radiological review as well as tumor volumetry
      was performed to assess the tumor's response to GKS. Tumors were characterized as
      either enlarged (> 15% volume increase), stable (follow-up volume +/- 15% of the
      initial volume), or decreased (> 15% volume decrease). A multivariate analysis
      was performed to determine factors related to each volume outcome group. RESULTS:
      Within the first month following GKS, a decrease was observed in 47.8% of the
      tumors. Tumor reduction varied according to carcinoma histopathological subtype,
      with 46.4% of non-small cell lung carcinomas, 70% of breast carcinomas, and 22.6%
      of melanomas showing volume reduction within 30 days after GKS. The mean volume
      decrease was 41.7%. For the remaining tumors, 41% were stable and 11.2% increased
      in volume. The overall analysis showed that there was a significant difference in
      percentage tumor change according to histopathological type (p < 0.001). There
      was a trend toward increased tumor reduction in those carcinoma types that are
      traditionally viewed as radiation sensitive (breast and non-small cell lung
      carcinomas). CONCLUSIONS: Gamma Knife surgery can offer patients early
      substantial volume reduction in many brain metastases. In instances in which
      early volume reduction of limited intracranial disease is desired, GKS may be
      used alone or before whole brain radiation therapy.

PMID- 18821833
TI  - "The mute who can sing": a cortical stimulation study on singing.
AB  - OBJECT: In an attempt to identify cortical areas involved in singing in addition
      to language areas, the authors used a singing task during direct cortical mapping
      in 5 patients who were amateur singers and had undergone surgery for brain
      tumors. The organization of the cortical areas involved in language and singing
      was analyzed in relation with these surgical data. METHODS: One left-handed and 4
      right-handed patients with brain tumors in left (2 cases) and right (3 cases)
      hemispheres and no significant language or singing deficits underwent surgery
      with the "awake surgery" technique. All patients had a special interest in
      singing and were involved in amateur singing activities. They were tested using
      naming, reading, and singing tasks. RESULTS: Outside primary sensorimotor areas,
      singing interferences were rare and were exclusively localized in small cortical
      areas (< 1 cm(2)). A clear distinction was found between speech and singing in
      the Broca region. In the Broca region, no singing interference was found in areas
      in which interference in naming and reading tasks were detected. Conversely, a
      specific singing interference was found in nondominant middle frontal gyri in one
      patient. This interference consisted of abrupt singing arrest without apparent
      face, mouth, and tongue contraction. Finally, nonspecific singing interferences
      were found in the right and left precentral gyri in all patients (probably by
      interference in final articulatory mechanisms of singing). CONCLUSIONS:
      Dissociations between speech and singing found outside primary sensorimotor areas
      showed that these 2 functions use, in some cortical stages, different cerebral
      pathways.

PMID- 18821834
TI  - MicroNester coil for neurointervention.
AB  - A MicroNester coil (MNC) was developed from the Nester coil with a 0.018-in
      microcatheter. The most specific feature of the MNC is the extended length of 14
      cm. Neurointervention involving the MNC was undertaken in 11 patients.
      Intervention procedures were transvenous embolization for a dural arteriovenous
      fistula in 4 patients, transarterial embolization for a dural arteriovenous
      fistula in 2, parent artery occlusion for a cerebral aneurysm in 4, and stent
      assisted embolization for a carotid artery dissection in 1. A push technique
      through microcatheter was used to deploy the MNCs. The MNCs were successfully
      placed into the venous sinus lesion, feeding artery, parent artery of the
      aneurysm, and the pseudoaneurysm. There were no major technical complications
      resulting in morbidity. The postoperative course was uneventful except in 2 cases
      in which the occluded vessel recanalized. Use of MNCs was safe and feasible for
      embolization of cerebrovascular lesions. Fewer coils are required in embolization
      when using MNCs.

PMID- 18821835
TI  - Endovascular intervention for acute thromboembolic stroke in young patients: an
      ideal population for aggressive intervention?
AB  - OBJECT: Endovascular treatment of acute thromboembolic stroke is a rapidly
      developing field that appears to hold great promise. Young patients may be
      particularly suited to benefit from endovascular acute stroke therapy. The
      authors sought to identify outcomes in young patients with thromboembolic stroke
      who underwent endovascular intervention. METHODS: The authors retrospectively
      reviewed a prospectively collected endovascular intervention registry of patients
      with ischemic strokes treated at a single large-volume institution between
      December 2000 and June 2007 to identify patients 18-35 years of age who were
      treated for thromboembolic stroke. Data are presented as the mean +/- standard
      deviation unless otherwise noted. RESULTS: Seven young patients underwent 8
      consecutive endovascular interventions for thromboembolic stroke (mean age 26 +/-
      6 years; 5 women). The National Institutes of Health Stroke Scale score at
      presentation was 13 +/- 4.3 (median 13). All patients presented within 6 hours of
      symptom onset. Revascularization was attempted with mechanical
      thrombectomy/disruption, intraarterial thrombolysis, and/or angioplasty, with or
      without stent placement. The modified Rankin Scale (mRS) score at discharge was
      2.2 +/- 1.5 (median 1.5), with 5 patients (62.5%) achieving independence at
      discharge (mRS Score 0-2). There were no deaths. Hospital length of stay was 6.5
      +/- 3.7 days (4.4 +/- 1.5 days for patients with an mRS score of 0-2; 10 +/- 3.6
      days for patients with an mRS score of 4). All patients became independent and
      had reached an mRS score of < or = 2 at last follow-up evaluation (29 +/- 25
      months). CONCLUSIONS: The data demonstrate the relative safety of endovascular
      intervention in young patients with thromboembolic cerebral ischemia and may
      suggest a potential benefit in outcome. Further investigation is indicated with
      larger numbers of patients and an appropriate control population.

PMID- 18821836
TI  - Eagle syndrome as a cause of transient ischemic attacks.
AB  - Eagle syndrome is an uncommon entity but is well known in the otorhinolaryngology
      and oral surgery literature. This syndrome results from the compression of
      cranial nerves in the neck by an elongated styloid process causing unilateral
      cervical and facial pain. The styloid process can also cause compression of the
      cervical carotid arteries leading to the so-called carotid artery syndrome
      together with carotidynia or neurological symptoms due to flow reduction in these
      arteries. The authors discuss the case of a 70-year-old man who suffered from
      transient ischemic attacks on turning his head to the left, with immediate
      remission of symptoms when his head returned to the neutral position. The patient
      was studied with dynamic angiography, which clearly showed focal flow
      restriction. Once a diagnosis was made, the styloid process was removed
      surgically and the patient completely recovered from his symptoms. A
      postoperative angiogram demonstrated complete resolution of the pathology.
      Neurosurgeons might encounter patients with Eagle syndrome and should be aware of
      the symptoms and signs. Once the diagnosis is made, the treatment is clear and
      very effective.

PMID- 18821837
TI  - Hyperinsulinemic euglycemia therapy for stunned myocardium following subarachnoid
      hemorrhage.
AB  - The authors describe the clinical course of a 50-year-old woman who presented
      with life-threatening cardiac dysfunction after aneurysmal subarachnoid
      hemorrhage (Fisher Grade 4). The pathophysiology of cardiac injury in this
      setting is not fully understood, but excess sympathetic activation can lead to
      neurogenic stressed myocardium. A metabolic intervention using the continuous
      intravenous infusion of high doses of insulin with euglycemia resulted in a rapid
      improvement of cardiac contractility. The observed benefit could be due to better
      myocardial glucose utilization that could not have been achieved by catecholamine
      administration.

PMID- 18821838
TI  - Using mechanistic models to understand synchrony in forest insect populations:
      the North American gypsy moth as a case study.
AB  - In many forest insects, subpopulations fluctuate concurrently across large
      geographical areas, a phenomenon known as population synchrony. Because of the
      large spatial scales involved, empirical tests to identify the causes of
      synchrony are often impractical. Simple models are, therefore, a useful aid to
      understanding, but data often seem to contradict model predictions. For instance,
      chaotic population dynamics and limited dispersal are not uncommon among
      synchronous forest defoliators, yet both make it difficult to achieve synchrony
      in simple models. To test whether this discrepancy can be explained by more
      realistic models, we introduced dispersal and spatially correlated stochasticity
      into a mechanistic population model for the North American gypsy moth Lymantria
      dispar. The resulting model shows both chaotic dynamics and spatial synchrony,
      suggesting that chaos and synchrony can be reconciled by the incorporation of
      realistic dynamics and spatial structure. By relating alterations in model
      structure to changes in synchrony levels, we show that the synchrony is due to a
      combination of spatial covariance in environmental stochasticity and the origins
      of chaos in our multispecies model.

PMID- 18821839
TI  - Movement strategies of seed predators as determinants of plant recruitment
      patterns.
AB  - Plant recruitment in nature exhibits several distinctive patterns ranging from
      hump shaped to monotonically decreasing with distance from the seed source. We
      investigate the role of postdispersal seed predation in shaping these patterns,
      introducing a new mechanistic model that explicitly accounts for the movement
      strategy used by seed eaters. The model consists of two partial differential
      equations describing the spatiotemporal dynamics of both seed and predator
      densities. The movement strategy is defined by how predators move in response to
      the different cues they can use to search for seeds. These cues may be seed
      density, seed intake, distance from the plant, density of conspecific foragers,
      or a mixture of these four. The model is able to reproduce all the basic plant
      recruitment patterns found in the field. We compare the results to those of the
      ideal free distribution (IFD) theory and show that hump-shaped plant recruitment
      patterns cannot be generated by IFD predators and, in general, by foragers that
      respond exclusively to seed density. These foragers can produce only
      nonincreasing patterns, the shapes of which are determined by the foragers'
      navigation capacities. In contrast, hump-shaped patterns can be produced by
      distance-responsive predators or by foragers that use conspecifics as a cue for
      seed abundance.

PMID- 18821840
TI  - Sea snakes (Laticauda spp.) require fresh drinking water: implication for the
      distribution and persistence of populations.
AB  - Dehydration and procurement of water are key problems for vertebrates that have
      secondarily invaded marine environments. Sea snakes and other marine reptiles are
      thought to remain in water balance without consuming freshwater, owing to the
      ability of extrarenal salt glands to excrete excess salts obtained either from
      prey or from drinking seawater directly. Contrary to this long-standing dogma, we
      report that three species of sea snake actually dehydrate in marine environments.
      We investigated dehydration and drinking behaviors in three species of amphibious
      sea kraits (Laticauda spp.) representing a range of habits from semiterrestrial
      to very highly marine. Snakes that we dehydrated either in air or in seawater
      refused to drink seawater but drank freshwater or very dilute brackish water (10%
      30% seawater) to remain in water balance. We further show that Laticauda spp. can
      dehydrate severely in the wild and are far more abundant at sites where there are
      sources of freshwater. A more global examination of all sea snakes demonstrates
      that species richness correlates positively with mean annual precipitation within
      the Indo-West Pacific tropical region. The dependence of Laticauda spp. on
      freshwater might explain the characteristically patchy distributions of these
      reptiles and is relevant to understanding patterns of extinctions and possible
      future responses to changes in precipitation related to global warming. In
      particular, metapopulation dynamics of the Laticauda group of sea snakes are
      expected to change in relation to projected reductions of tropical dry-season
      precipitation.

PMID- 18821842
TI  - Optimization of amniotic membrane (AM) denuding for tissue engineering.
AB  - INTRODUCTION: Amniotic membrane (AM) has gained increasing popularity as a useful
      carrier for ex vivo-expanded cells for tissue engineering, particularly in ocular
      surface reconstruction. However, current methods employed for denuding AM are
      highly variable, and the consequent effects on the structural and molecular
      composition of the AM basement membrane (BM) are ambiguous. We compare the
      effects of the main denuding procedures, and propose a highly effective
      standardized alternative. METHODS: AMs preserved for transplantation were denuded
      using published ethylenediaminetetraacetic acid (EDTA)- and dispase-based
      methodologies and our novel thermolysin-based procedure. Scanning and
      transmission electron microscopy and immunohistochemistry, for BM components
      (collagens IV and VII, laminin 5, and integrins alpha6 and beta4), were used to
      assess effectiveness of denuding epithelium, whilst maintaining the integrity of
      the BM. RESULTS: EDTA- and dispase-based denuding techniques resulted in the
      disaggregation and even destruction of the BM structure and molecular
      composition. Employing thermolysin effectively denuded epithelium whilst
      maintaining BM structural and molecular integrity. CONCLUSION: Current procedures
      for preparing AM are variable and often ineffective, resulting in nonstandard
      membranes. Our novel thermolysin-based technique effectively denudes the AM
      whilst preserving an essentially intact and consistent BM. Therefore, we propose
      that this novel thermolysin procedure may potentially improve overall generation
      of tissue-engineered constructs using AM.

PMID- 18821841
TI  - Stem cells for heart cell therapies.
AB  - Myocardial infarction-induced heart failure is a prevailing cause of death in the
      United States and most developed countries. The cardiac tissue has extremely
      limited regenerative potential, and heart transplantation for reconstituting the
      function of damaged heart is severely hindered mainly due to the scarcity of
      donor organs. To that end, stem cells with their extensive proliferative capacity
      and their ability to differentiate toward functional cardiomyocytes may serve as
      a renewable cellular source for repairing the damaged myocardium. Here, we review
      recent studies regarding the cardiogenic potential of adult progenitor cells and
      embryonic stem cells. Although large strides have been made toward the
      engineering of cardiac tissues using stem cells, important issues remain to be
      addressed to enable the translation of such technologies to the clinical setting.

PMID- 18821843
TI  - Bioreactor maintained living skin matrix.
AB  - Numerous reconstructive procedures result in wounds that require skin grafting.
      Often, the amount of tissue available from donor sites is limited. In vivo tissue
      expanders have been used clinically to generate larger sections of skin, and
      other methods exist to cover large wounds, but all have significant limitations.
      We investigated whether these difficulties could be overcome by increasing the
      surface area of skin in vitro while maintaining tissue viability. Human foreskin
      was incrementally expanded in a computer-controlled bioreactor system over 6 days
      to increase its surface dimensions under culture conditions. Morphological,
      ultrastructural, and mechanical properties of the foreskin were evaluated before
      and after expansion using histology, scanning electron microscopy, mercury
      porosimetry, and tensile testing. The surface area of the tissue was 110.7% +/-
      12.2% greater, with maintenance of cell viability and proliferative potential.
      Histomorphological and ultrastructural analyses showed that dermal structural
      integrity was preserved. The pore diameter of the expanded skin was 64.49% +/-
      32.8% greater. The mechanical properties were not adversely affected. These
      findings show that expansion of living skin matrices can be achieved using a
      computer-controlled bioreactor system. This technique provides an opportunity to
      generate large amounts of skin for reconstructive procedures.

PMID- 18821844
TI  - Effect of scaffold stiffness on myoblast differentiation.
AB  - Successful tissue engineering requires optimization of scaffold stiffness for a
      given application and cell type. Here, we investigated the effect of scaffold
      stiffness on myoblast cells, demonstrating the ability of cells to affect and to
      sense their mechanical microenvironment. Myoblasts were cultured on composite
      three-dimensional poly-lactic acid (PLLA)/poly-lactic co glycolic acid (PLGA)
      porous scaffolds of varied elasticity. The elasticity was controlled by changing
      the ratio of PLLA versus PLGA in the scaffolds. Cell organization, myotube
      formation, and cell viability were affected by scaffold stiffness. PLLA
      containing scaffolds (100% to 25% PLLA) provided stiffness that supported myotube
      formation, while neat PLGA scaffold failed to support myotube formation and cell
      viability. Furthermore, scaffold stiffness correlated to its size/area reduction
      upon culturing experiments, suggesting different shrinkage degree by cell forces.
      Inhibition of scaffold shrinking by affixing device resulted in spacious cell
      organization with normal cell morphology. This may suggest that scaffold
      shrinkage led to cellular degeneration and shape deformation. Our results
      indicate that compliant scaffolds are insufficient to withstand cell forces. On
      the other hand, excessively firm scaffold could not lead to parallel oriented
      myotube organization. Hence, optimal scaffold stiffness can be tailored by
      PLLA/PLGA blending to direct specific stages of myoblast differentiation and
      organization.

PMID- 18821845
TI  - Full-length genome characterization of an HIV type 2 isolate from India.
AB  - An infectious Indian human immunodeficiency virus-2 (HIV-2) subtype A isolate was
      completely sequenced and analyzed and its phylogenetic relatedness was
      investigated. The unusual limited size of the long terminal repeat (LTR) from the
      isolate was caused due to a truncation within the nef open reading frame (ORF)
      located at the U3 region of the LTR. The genetic relatedness and lineage of this
      HIV-2 strain were investigated. The close relatedness of this isolate to West
      African HIV-2 isolates confirms a geographical entry route of HIV-2 to this part
      of the Indian subcontinent. This is the first report of an HIV-2 full genome
      analysis from the Indian subcontinent as well as from Asia.

PMID- 18821846
TI  - Manganese superoxide dismutase V16A single-nucleotide polymorphism in the
      mitochondrial targeting sequence is associated with reduced enzymatic activity in
      cryopreserved human hepatocytes.
AB  - Mitochondrial manganese superoxide dismutase (MnSOD), encoded by the SOD2 gene,
      represents a major cellular defense against environmental carcinogens that cause
      oxidative stress. Two single-nucleotide polymorphisms -9 T>C (V16A in the MnSOD
      mitochondrial targeting sequence) and -102 C>T (in the SOD2 promoter sequence)
      modify risk toward various types of malignancies and overall survival. Since
      little is known about the effects of these polymorphisms on overall enzyme
      function in normal human tissue, the goal of this study was to evaluate their
      functional effects in cryopreserved human hepatocytes. Cryopreserved human
      hepatocytes were genotyped for the MnSOD -9 T>C and -102 C>T polymorphisms by
      TaqMan allelic discrimination assays. MnSOD catalytic activities were determined
      in vitro in lysates derived from the hepatocytes. In random samplings of
      cryopreserved hepatocytes, 16% possessed the -9 T>C and 6% possessed polymorphism
      on at least one of the two alleles. -9 T>C (V16A) significantly (p < 0.02)
      reduced MnSOD catalytic activity whereas -102 C>T did not (p > 0.05). The -9 T>C
      (V16A) polymorphism in the MnSOD mitochondrial targeting sequence significantly
      reduced MnSOD catalytic activity in cryopreserved hepatocytes, consistent with
      its reported associations with cancer risk and treatment.

PMID- 18821847
TI  - Suppression of dendritic cell activation by anthrax lethal toxin and edema toxin
      depends on multiple factors including cell source, stimulus used, and function
      tested.
AB  - Bacillus anthracis produces lethal toxin (LT) and edema toxin (ET), and they
      suppress the function of LPS-stimulated dendritic cells (DCs). Because DCs
      respond differently to various microbial stimuli, we compared toxin effects in
      bone marrow DCs stimulated with either LPS or Legionella pneumophila (Lp). LT,
      not ET, was more toxic for cells from BALB/c than from C57BL/6 (B6) as measured
      by 7-AAD uptake; however, ET suppressed CD11c expression. LT suppressed IL-12, IL
      6, and TNF-alpha in cells from BALB/c and B6 mice but increased IL-1beta in LPS
      stimulated cultures. ET also suppressed IL-12 and TNF-alpha, but increased IL-6
      and IL-1beta in Lp-stimulated cells from B6. Regarding maturation marker
      expression, LT increased MHCII and CD86 while suppressing CD40 and CD80; ET
      generally decreased marker expression across all groups. We conclude that the
      suppression of cytokine production by anthrax toxins is dependent on variables,
      including the source of the DCs, the type of stimulus and cytokine measured, and
      the individual toxin tested. However, LT and ET enhancement or suppression of
      maturation marker expression is more related to the marker studied than the
      stimuli or cell source. Anthrax toxins are not uniformly suppressive of DC
      function but instead can increase function under defined conditions.

PMID- 18821848
TI  - Premature apoptosis of Chlamydia-infected cells disrupts chlamydial development.
AB  - The obligate intracellular development of Chlamydia suggests that the bacteria
      should be vulnerable to premature host cell apoptosis, but because Chlamydia
      infected cells are apoptosis resistant, this has never been able to be tested. We
      have devised a system to circumvent the apoptotic block imposed by chlamydial
      infection. When the proapoptotic protein Bim(S) was experimentally induced,
      epithelial cells underwent apoptosis that was not blocked by chlamydial
      infection. Apoptosis during the developmental cycle prevented the generation of
      infectious bacteria and caused transcriptional changes of bacterial genes and
      loss of intracellular ATP. Intriguingly, although apoptosis resulted in
      destruction of host cell structures and of the Chlamydia inclusion, and prevented
      generation of elementary bodies, Bim(S) induction in the presence of a caspase
      inhibitor allowed differentiation into morphologically normal but noninfectious
      elementary bodies. These data show that chlamydial infection renders host cells
      apoptosis resistant at a premitochondrial step and demonstrate the consequences
      of premature apoptosis for development of the bacteria.

PMID- 18821849
TI  - Danger ahead: politics intrude in Infectious Diseases Society of America
      guideline for Lyme disease.

PMID- 18821851
TI  - Apolipoprotein(a) stimulates vascular endothelial cell growth and migration and
      signals through integrin alphaVbeta3.
AB  - Elevated plasma concentrations of Lp(a) [lipoprotein(a)] are an emerging risk
      factor for atherothrombotic disease. Apo(a) [apolipoprotein(a)], the unique
      glycoprotein component of Lp(a), contains tandem repeats of a plasminogen kringle
      (K) IV-like domain. In the light of recent studies suggesting that apo(a)/Lp(a)
      affects endothelial function, we evaluated the effects of apo(a)/Lp(a) on growth
      and migration of cultured HUVECs (human umbilical-vein endothelial cells). Two
      full-length r-apo(a) [recombinant apo(a)] variants (12K and 17K), as well as
      Lp(a), were able to stimulate HUVEC growth and migration to a comparable extent;
      17K r-apo(a) also decreased the levels of total and active transforming growth
      factor-beta secreted by these cells. Using additional r-apo(a) variants
      corresponding to deletions and/or site-directed mutants of various kringle
      domains in the molecule, we were able to determine that the observed effects of
      full-length r-apo(a) on HUVECs were dependent on the presence of a functional
      lysine-binding site(s) in the apo(a) molecule. With respect to signalling events
      elicited by apo(a) in HUVECs, we found that 17K treatment of the cells increased
      the phosphorylation level of FAK (focal adhesion kinase) and MAPKs (mitogen
      activated protein kinases), including ERK (extracellular-signal-regulated
      kinase), p38 and JNK (c-Jun N-terminal kinase). In addition, we showed that
      LM609, the function-blocking antibody to integrin alphaVbeta3, abrogated the
      effects of 17K r-apo(a) and Lp(a) on HUVECs. Taken together, the results of the
      present study suggest that the apo(a) component of Lp(a) signals through integrin
      alphaVbeta3 to activate endothelial cells.

PMID- 18821852
TI  - Characterization of cytochrome bo3 activity in a native-like surface-tethered
      membrane.
AB  - We have developed a simple native-like surface-tethered membrane system to
      investigate the activity of cbo(3) (cytochrome bo(3)), a terminal oxidase in
      Escherichia coli. The tethered membranes consist of E. coli inner-membrane
      extracts mixed with additional E. coli lipids containing various amounts of the
      cbo(3) substrate UQ-10 (ubiquinol-10). Tethered membranes are formed by self
      assembly from vesicles on to gold electrodes functionalized with cholesterol
      derivatives. cbo(3) activity was monitored using CV (cyclic voltammetry) with
      electron transfer to cbo(3) mediated by UQ-10. The apparent K(m) for oxygen with
      this system is 1.1+/-0.4 microM, in good agreement with values reported in the
      literature for whole-cell experiments and for purified cbo(3). Increasing the
      concentration of lipophilic UQ-10 in the membrane leads to an increase in cbo(3)
      activity. The activity of cbo(3) with long-chain ubiquinones appears to be
      different from previous reports using short-chain substrate analogues such as UQ
      1 in that typical Michaelis-Menten kinetics are not observed using UQ-10. This
      native-like membrane model thus provides new insights into the interaction of
      transmembrane enzymes with hydrophobic substrates which contrasts with studies
      using hydrophilic UQ analogues.

PMID- 18821853
TI  - Hyperbaric oxygen activates discoidin domain receptor 2 via tumour necrosis
      factor-alpha and the p38 MAPK pathway to increase vascular smooth muscle cell
      migration through matrix metalloproteinase 2.
AB  - DDR2 (discoidin domain receptor 2) regulates collagen turnover mediated by SMCs
      (smooth muscle cells) in atherosclerosis. HBO (hyperbaric oxygen) has been used
      in medical practice; however, the molecular mechanism of the beneficial effects
      of HBO is poorly understood. Furthermore, the effect of HBO on DDR2 has not been
      reported previously. In the present study, we investigated the cellular and
      molecular mechanisms of DDR2 regulation by HBO in VSMCs (vascular SMCs). Cells
      were exposed to 2.5 ATA (atmosphere absolute) of oxygen in a hyperbaric chamber.
      DDR2 protein (3.63-fold) and mRNA (2.34-fold) expression were significantly
      increased after exposure to 2.5 ATA HBO for 1 h. Addition of SB203580 and p38
      MAPK (mitogen-activated protein kinase) siRNA (small interfering RNA) 30 min
      before HBO inhibited the induction of DDR2 protein. HBO also significantly
      increased DNA-protein binding activity of Myc/Max. Addition of SB203580 and an
      anti-TNF-alpha (tumour necrosis factor-alpha) monoclonal antibody 30 min before
      HBO abolished the DNA-protein binding activity induced by HBO. HBO significantly
      increased the secretion of TNF-alpha from cultured VSMCs. Exogenous addition of
      TNF-alpha significantly increased DDR2 protein expression, whereas anti-TNF-alpha
      and anti-(TNF-alpha receptor) antibodies blocked the induction of DDR2 protein
      expression. HBO significantly increased VSMC migration and proliferation, whereas
      DDR2 siRNA inhibited the migration induced by HBO. HBO increased activated MMP2
      (matrix metalloproteinase 2) protein expression, and DDR2 siRNA abolished the
      induction of activated MMP2 expression induced by HBO. In conclusion, HBO
      activates DDR2 expression in cultured rat VSMCs. HBO-induced DDR2 is mediated by
      TNF-alpha and at least in part through the p38 MAPK and Myc pathways.

PMID- 18821850
TI  - Redox control of renal function and hypertension.
AB  - Loss of redox homeostasis and formation of excessive free radicals play an
      important role in the pathogenesis of kidney disease and hypertension. Free
      radicals such as reactive oxygen species (ROS) are necessary in physiologic
      processes. However, loss of redox homeostasis contributes to proinflammatory and
      profibrotic pathways in the kidney, which in turn lead to reduced vascular
      compliance and proteinuria. The kidney is susceptible to the influence of various
      extracellular and intracellular cues, including the renin-angiotensin-aldosterone
      system (RAAS), hyperglycemia, lipid peroxidation, inflammatory cytokines, and
      growth factors. Redox control of kidney function is a dynamic process with
      reversible pro- and anti-free radical processes. The imbalance of redox
      homeostasis within the kidney is integral in hypertension and the progression of
      kidney disease. An emerging paradigm exists for renal redox contribution to
      hypertension.

PMID- 18821854
TI  - Tanning, p53 and PCMR.

PMID- 18821856
TI  - Are tanning beds "safe"? Human studies of melanoma.
AB  - Controversy continues over the carcinogenic properties of tanning beds. The
      tanning industry "sells" tanning beds as a safe alternative to UV exposure for
      both tanning as well as vitamin D biosynthesis. But, how safe are tanning beds?
      Epidemiologic data - incomplete and unsatisfactory - suggests that tanning beds
      are not safer than solar ultraviolet radiation and that they may have independent
      effects from solar exposure that increase risk for melanoma.

PMID- 18821855
TI  - UV and pigmentation: molecular mechanisms and social controversies.
AB  - Ultraviolet radiation (UVR) is an essential risk factor for the development of
      premalignant skin lesions as well as of melanoma and non-melanoma skin cancer.
      UVR exerts many effects on the skin, including tanning, carcinogenesis,
      immunomodulation, and production of vitamin D. Vitamin D (vit D) is important in
      the maintenance of healthy bones as well as other purported beneficial effects,
      amongst which is the potential for reducing risk of malignancy--though oral
      supplementation is fully capable of maintaining systemic levels. The known
      medical harm from UV exposure relates primarily to cancer of the skin--the most
      common organ in man to be affected by cancer. In this review, we summarize the
      knowledge about the ultraviolet (UV) response in regards to inflammation,
      immunosuppression, carcinogenesis and the tanning response. We also discuss vit D
      and UV, as well as public health implications of tanning behavior and commercial
      interests related to the promotion of UV exposure. As the most ubiquitous human
      carcinogen, UVR exposure represents both a challenge and enormous opportunity in
      the realm of skin cancer prevention.

PMID- 18821857
TI  - Ultraviolet wavebands and melanoma initiation.
AB  - In view of claims that ultraviolet radiation-emitting sunbeds are safe, or safe
      when they emit only longer wavelengths, research findings are reviewed here on
      the effects of ultraviolet wavebands A and B (UVA, 315-400 nm and UVB, 290-315
      nm) on mutagenesis and carcinogenesis in skin, with particular reference to
      melanocytes and melanoma. Both UVA and UVB radiation have been shown to induce
      mutations, as well as mutagenic photoproducts such as cyclobutane pyrimidine
      dimers, in human skin. UVB can induce melanoma in susceptible mice and in
      xenografted human skin engineered to express melanocyte growth factors. There is
      evidence for photosensitization of melanocytes by melanin, especially
      pheomelanin. UVA can induce melanoma in pigmented fish, and melanocytic
      hyperplasia in pigmented opossums, but has not generally been tested for melanoma
      induction in pigmented mammals or in human skin. There is no experimental basis
      for a claim that UVA is safe, and recreational exposure to this known mutagen
      should be discouraged.

PMID- 18821858
TI  - Molecular diagnosis of oculocutaneous albinism: new mutations in the OCA1-4 genes
      and practical aspects.

PMID- 18821859
TI  - Tandem measurement of D-dimer and myeloperoxidase or C-reactive protein to
      effectively screen for pulmonary embolism in the emergency department.
AB  - OBJECTIVES: The hypothesis was that the tandem measurement of D-dimer and
      myeloperoxidase (MPO) or C-reactive protein (CRP) could significantly decrease
      unnecessary pulmonary vascular imaging in emergency department (ED) patients
      evaluated for pulmonary embolism (PE) compared to D-dimer alone. METHODS: The
      authors measured the sequential combinations of D-dimer and MPO and D-dimer and
      CRP in a prospective sample of ED patients evaluated for PE at two centers.
      Patients were followed for 90 days for venous thromboembolism (VTE, either PE or
      deep venous thrombosis [DVT]), which required the consensus of two of three
      blinded physician reviewers. RESULTS: The authors enrolled 304 patients, 22 with
      VTE (7%; 95% confidence interval [CI] = 5% to 10%). The sensitivity and
      specificity of a D-dimer alone (cutoff > or = 500 ng/mL) were 100% (95% CI = 85%
      to 100%) and 59% (95% CI = 53% to 65%), respectively, and was followed by
      pulmonary vascular imaging negative for PE in 38% (115/304; 95% CI = 32% to 44%).
      The combination of either a negative D-dimer, or MPO < 22 mg/dL, had a
      sensitivity of 100% and specificity of 73% (95% CI = 67% to 78%). Thus, tandem
      measurement of D-dimer and MPO would have decreased the frequency of subsequent
      negative pulmonary vascular imaging from 38% to 25% (95% CI of the difference of 
      13% = -5% to -20%). The combination of CRP and D-dimer would not have
      significantly improved the rate of negative imaging. CONCLUSIONS: The tandem
      measurement of D-dimer and MPO would have significantly decreased negative
      pulmonary vascular imaging compared with D-dimer alone and should be validated
      prospectively.

PMID- 18821860
TI  - Pediatric emergency department overcrowding and impact on patient flow outcomes.
AB  - BACKGROUND: Understanding the impact of overcrowding in pediatric emergency
      departments (PEDs) on quality of care is a growing concern. Boarding admitted
      patients in the PED and increasing emergency department (ED) visits are two
      potentially significant factors affecting quality of care. OBJECTIVES: The
      objective was to describe the impact ED boarding time and daily census have on
      the timeliness of care in a PED. METHODS: Pediatric ED boarding time and daily
      census were determined each day from July 2003 to July 2007. Outcome measures
      included mean length of stay (LOS), time to triage, time to physician, and
      patient elopement during a 24-hour period. RESULTS: For every 50 patients seen
      above the average daily volume of 250, LOS increased 14.8 minutes, time to triage
      increased 6.6 minutes, time to physician increased 18.2 minutes, and number of
      patient elopements increased by three. For each increment of 24 hours to total ED
      boarding time, LOS increased 7.6 minutes, time to triage increased 0.6 minutes,
      time to physician increased 3 minutes, and number of patient elopements increased
      by 0.6 patients. CONCLUSIONS: ED boarding time and ED daily census show
      independent associations with increasing overall LOS, time to triage, time to
      physician, and number of patient elopements in a PED.

PMID- 18821861
TI  - International emergency medicine: a review of the literature from 2007.
AB  - The subspecialty of international emergency medicine (IEM) continues to grow
      within the United States, just as the specialty of emergency medicine (EM)
      continues to spread to both developed and developing countries around the world.
      One of the greatest obstacles, however, faced by IEM researchers and
      practitioners alike, remains the lack of a high-quality, consolidated, and easily
      accessible evidence-base of literature. In response to this perceived need,
      members of the Emergency Medicine Resident Association (EMRA) International
      Emergency Medicine Committee, in conjunction with members of the Society for
      Academic Emergency Medicine (SAEM) International Health Interest Group, have
      embarked on the task of creating a recurring review of IEM literature. This
      publication represents the third annual review, covering the top 30 IEM research
      articles published in 2007. Articles were selected for the review according to
      explicit, predetermined criteria that included both methodologic quality and
      perceived impact of the research. It is hoped that this annual review will act as
      a forum for disseminating best practices, while also stimulating further research
      in the field of IEM.

PMID- 18821862
TI  - Mechanical ventilation was associated with acidemia in a case series of
      salicylate-poisoned patients.
AB  - OBJECTIVES: Despite little empiric evidence, mechanical ventilation (MV) in the
      setting of salicylate poisoning is considered by many to be harmful. When
      salicylate-poisoned patients are ventilated at conventional settings, the
      respiratory alkalosis is abolished, more salicylate is able to pass into the
      central nervous system (CNS), and neurotoxicity worsens. The objective of this
      study was to identify a relationship between MV, acidosis, and outcome in
      salicylate-poisoned patients. METHODS: The authors electronically searched a
      poison control center (PCC) database (2001-2007) for patients with salicylate
      poisoning, defined as a serum concentration > 50 mg/dL, who had MV listed as a
      therapy. For the 7-year study period, a total of 3,144 salicylate-poisoning cases
      were identified. Eleven patients met the inclusion criteria of having both
      salicylate concentrations > 50 mg/dL and required MV; only 7 of them had post-MV
      data available. RESULTS: In all seven patients with post-MV blood gas data, the
      post-MV pH was < 7.4. In five of six patients with recorded PCO2, the post-MV
      PCO2 was > 50 mm Hg. Two of the seven patients in the study group died following
      intubation (two patients died within 3 hours [serum salicylate concentrations, 85
      and 79 mg/dL, respectively]). Another patient sustained severe neurologic injury
      (serum salicylate concentration, 84 mg/dL). The other four patients were
      ultimately discharged home. In the three patients with the worst clinical
      outcome, deterioration was reported within hours of intubation. CONCLUSIONS:
      Inadequate MV of patients with salicylate poisoning is associated with
      respiratory acidosis, acidemia, and clinical deterioration in this series of
      cases. This supports warnings about the danger of improper MV in patients with
      salicylate poisoning. A prospective study should be performed.

PMID- 18821863
TI  - Emergency department bedside echocardiography in diagnosis of Ebstein's anomaly
      with Wolff-Parkinson-White syndrome and atrial fibrillation.

PMID- 18821864
TI  - Emergency department diagnosis of pericardial tamponade aided by goal-directed
      bedside echocardiography.

PMID- 18821865
TI  - Emergency bedside ultrasound diagnosis of traumatic cardiac tamponade--a case of
      blunt cardiac rupture.

PMID- 18821867
TI  - Abstracts from the 2008 council of residency directors academic assembly.

PMID- 18821866
TI  - Emergency bedside ultrasound diagnosis of nontraumatic cardiac tamponade--a case
      of Type A aortic dissection.

PMID- 18821868
TI  - Why do alcohol outlets matter anyway? A look into the future.

PMID- 18821869
TI  - No reason for optimism: the expected impact of commitments in the European
      Commission's Alcohol and Health Forum.
AB  - BACKGROUND: Europe is the heaviest-drinking region in the world, more than 2.5
      times the rest of the world's average. THE COMMISSION'S CONCLUSION: The
      cornerstone for the European Commission's action to decrease the alcohol-related
      harm of this consumption and the main emphasis for its work is the Alcohol and
      Health Forum, with its Task Forces on Marketing Communication and Youth-Specific
      Aspects of Alcohol. The Forum, which was launched in June 2007, aims to provide a
      common platform for all interested stakeholders. Forum members are invited to
      make commitments to reduce alcohol-related harm, in the form of a monitored and
      evaluated action plan. By 29 February 2008, 79 commitments have been provided by
      the members of the Forum. APPRAISAL OF THE INITIATIVE: Taking into account the
      limited information available, the proposed commitments indicate few evidence
      based approaches. A large majority of the summaries do not, or only slightly,
      address the relevance of their commitment and give no evidence of why their
      proposed action is important in reducing alcohol-related harm. Even fewer
      commitments mention indicators of effectiveness of the proposed actions or
      propose to evaluate the effectiveness of the proposed actions. CONCLUSION: While
      most economic operators in the Forum have resources to undertake actions which
      could be highly effective, they commit principally to educational programmes
      which have been found to be mainly ineffective. This, and the neglect of existing
      legislation, do not give reason for optimism on the impact of the proposed
      commitments.

PMID- 18821870
TI  - The social production of hepatitis C risk among injecting drug users: a
      qualitative synthesis.
AB  - BACKGROUND: Intervention impact on reductions in hepatitis C virus (HCV)
      incidence among injecting drug users (IDUs) are modest. There is a need to
      explore how drug injectors' interpret HCV risk. AIMS: To review English-language
      qualitative empirical studies of HCV risk among IDUs. METHODS: Qualitative
      synthesis using a meta-ethnographic approach. Searching of eight electronic
      databases and reference lists identified manually papers in peer-reviewed
      journals since 2000. Only studies investigating IDU perspectives on HCV risk were
      included. Themes across studies were identified systematically and compared,
      leading to a synthesis of second- and third-order constructs. FINDINGS: We
      included 31 papers, representing 24 studies among over 1000 IDUs. Seven themes
      were generated: risk ubiquity; relative viral risk; knowledge uncertainty;
      hygiene and the body; trust and intimacy; risk environment; and the
      individualization of risk responsibility. Evidence supports a perception of HCV
      as a risk accepted rather than avoided. HCV was perceived largely as socially
      accommodated and expected, and in relative terms to human immunodeficiency virus
      (HIV) as the 'master status' of viral dangers. Symbolic knowledge systems, rather
      than biomedical risk calculus, and especially narratives of hygiene and trust,
      played a primary role in shaping interpretations of HCV risk. Critical factors in
      the risk environment included policing, homelessness and gendered risk.
      CONCLUSIONS: Appealing to risk calculus alone is insufficient. Interventions
      should build upon the salience of hygiene and trust narratives in HCV risk
      rationality, and foster community changes towards the perceived preventability of
      HCV. Structural interventions in harm reduction should target policing,
      homelessness and gendered risk.

PMID- 18821871
TI  - Density of alcohol outlets and teenage drinking: living in an alcogenic
      environment is associated with higher consumption in a metropolitan setting.
AB  - AIM: This study examines the relationship between physical, socio-economic and
      social environments and alcohol consumption and drunkenness among a general
      population sample of drinkers aged 12-17 years. DESIGN, SETTING, PARTICIPANTS AND
      MEASURES: The study was conducted in Auckland, New Zealand. The design comprised
      two components: (i) environmental measures including alcohol outlet density,
      locality-based measure of willingness to sell alcohol (derived from purchase
      surveys of outlets) and a locality-based neighbourhood deprivation measure
      calculated routinely in New Zealand (known as NZDEP); and (ii) the second
      component was a random telephone survey to collect individual-level information
      from respondents aged 12-17 years including ethnicity, frequency of alcohol
      supplied socially (by parents, friends and others), young person's income;
      frequency of exposure to alcohol advertising; recall of brands of alcohol and
      self-reported purchase from alcohol outlets. A multi-level model was fitted to
      predict typical-occasion quantity, frequency of drinking and drunkenness in
      drinkers aged 12-17 years. FINDINGS: Typical-occasion quantity was predicted by:
      frequency of social supply (by parents, friends and others); ethnicity and outlet
      density; and self-reported purchasing approached significance. NZDEP was
      correlated highly with outlet density so could not be analysed in the same model.
      In a separate model, NZDEP was associated with quantity consumed on a typical
      drinking occasion. Annual frequency was predicted by: frequency of social supply
      of alcohol, self-reported purchasing from alcohol outlets and ethnicity. Feeling
      drunk was predicted by frequency of social supply of alcohol, self-reported
      purchasing from alcohol outlets and ethnicity; outlet density approached
      significance. Age and gender also had effects in the models, but retailers'
      willingness to sell to underage patrons had no effects on consumption, nor did
      the advertising measures. The young person's income was influential on typical
      occasion quantity once deprivation was taken into account. CONCLUSION: Alcohol
      outlet density was associated with quantities consumed among teenage drinkers in
      this study, as was neighbourhood deprivation. Supply by family, friends and
      others also predicted quantities consumed among underage drinkers and both social
      supply and self-reported purchase were associated with frequency of drinking and
      drunkenness. The ethnic status of young people also had an effect on consumption.

PMID- 18821872
TI  - Blood pressure reduction during treatment for alcohol dependence: results from
      the Combining Medications and Behavioral Interventions for Alcoholism (COMBINE)
      study.
AB  - AIMS: Heavy drinking is associated with hypertension. This study evaluated blood
      pressure changes occurring during treatment for alcohol dependence. PARTICIPANTS:
      Subjects included 1383 people participating in the Combining Medications and
      Behavioral Interventions for Alcoholism (COMBINE) study, a large multi-center
      treatment study for alcohol dependence. MEASUREMENTS: Methods appropriate for
      repeated-measures data were used to assess the relationship of percentage of
      drinking days (PDD) to systolic and diastolic blood pressure over a 16-week
      treatment period. Modification of these associations by demographic and other
      variables was assessed. FINDINGS: Blood pressure reduction was evident only in
      people who were above the median blood pressure at baseline. In this group,
      systolic blood pressure decreased by an average of 12 mmHg and diastolic blood
      pressure decreased by an average of 8 mmHg. Blood pressure reduction occurred
      during the first month of treatment. This effect was similar regardless of age,
      sex, body mass index, reported history of hypertension and use of anti
      hypertensive medications. An observed association between blood pressure and PDD
      in Caucasians was not evident in African Americans due largely to their lower pre
      treatment blood pressure. CONCLUSIONS: Reduction in alcohol consumption has a
      potent anti-hypertensive effect in alcoholics with higher blood pressure. For
      hypertensive, alcohol-dependent people, treatment for alcoholism should be
      considered a major component of anti-hypertensive therapy.

PMID- 18821873
TI  - Reducing youth alcohol drinking through a parent-targeted intervention: the
      Orebro Prevention Program.
AB  - AIMS: To evaluate a 2.5-year prevention programme working through parents,
      targeting drinking among 13-16-year-olds. DESIGN: Quasi-experimental using
      matched controls with a pre-post, intention-to-treat design. SETTING: Schools
      located in inner city, public housing and small town areas. PARTICIPANTS: A total
      of 900 pupils entering junior high school and their parents, followed
      longitudinally. INTERVENTION: Parents received information by mail and during
      parent meetings in schools urging them to: (i) maintain strict attitudes against
      youth alcohol use and (ii) encourage their youth's involvement in adult-led,
      organized activities. MEASUREMENTS: Evaluation of the implementation used
      measures of parental attitudes against underage drinking and youths'
      participation in organized activities. Outcomes were youths' drunkenness and
      delinquency. FINDINGS: The implementation successfully influenced parents'
      attitudes against underage drinking, but not youth participation in organized
      activities. At post-test, youths in the intervention group reported less
      drunkenness and delinquency. Effect sizes were 0.35 for drunkenness and 0.38 for
      delinquency. Findings were similar for boys and girls and for early starters.
      Effects were not moderated by community type. CONCLUSIONS: Working via parents
      proved to be an effective way to reduce underage drinking as well as delinquency.

PMID- 18821874
TI  - Risk and speed of transitions to first alcohol dependence symptoms in
      adolescents: a 10-year longitudinal community study in Germany.
AB  - BACKGROUND: Although in many western countries alcohol use (AU) and symptoms of
      alcohol dependence (AD) are frequent in adolescence, temporal patterns and
      trajectories remain understudied. It is unclear whether early onset of AU is
      associated with the speed of transition to first AD symptoms and whether specific
      first AD symptoms and their timing are associated with AD. AIMS: To examine (i)
      the incidence patterns of self-reported first AD symptoms; (ii) whether early AU
      is associated with the risk and speed of transition to first AD symptoms; and
      (iii) whether first AD symptoms and their timing are associated with AD. DESIGN:
      A total of 3021 community subjects from Germany aged 14-24 years at baseline
      followed prospectively over 10 years. AU, AD symptoms and AD were assessed using
      the Munich-Composite International Diagnostic Interview (DIA-X/M-CIDI). FINDINGS:
      Among first AD symptoms, tolerance (13.1%) and much time spent (5.0%) were most
      prevalent. Five to 30% of all first AD symptoms occurred during the first year
      after first AU. Early AU was not related to the risk of first AD symptoms. The
      speed of transition to first AD symptoms was greater among those with AU onset in
      later adolescence. Tolerance and loss of control were associated with AD
      development (risk difference 3.9% and 15.4%), as was early onset of tolerance,
      much time spent and loss of control. CONCLUSION: Early AU and early AD symptoms
      are frequent among adolescents. Early self-reported tolerance, much time spent
      and loss of control are particularly predictive for AD and important targets for
      early preventive interventions.

PMID- 18821875
TI  - Overdose training and take-home naloxone for opiate users: prospective cohort
      study of impact on knowledge and attitudes and subsequent management of
      overdoses.
AB  - AIM: To examine the impact of training in overdose management and naloxone
      provision on the knowledge and confidence of current opiate users; and to record
      subsequent management of overdoses that occur during a 3-month follow-up period.
      DESIGN: Repeated-measures design to examine changes in knowledge and confidence
      immediately after overdose management training; retention of knowledge and
      confidence at 3 months; and prospective cohort study design to document actual
      interventions applied at post-training overdose situations. METHOD: A total of
      239 opiate users in treatment completed a pre-training questionnaire on overdose
      management and naloxone administration and were re-assessed immediately post
      training, at which point they were provided with the take-home emergency supply
      of naloxone. Three months later they were re-interviewed. RESULTS: Significant
      improvements were seen in knowledge of risks of overdose, characteristics of
      overdose and appropriate actions to be taken; and in confidence in the
      administration of naloxone. A 78% follow-up rate was achieved (186 of 239) among
      whom knowledge of both the risks and physical/behavioural characteristics of
      overdose and also of recommended management actions was well retained. Eighteen
      overdoses (either experienced or witnessed) had occurred during the 3 months
      between the training and the follow-up. Naloxone was used on 12 occasions (a
      trained client's own supply on 10 occasions). One death occurred in one of the
      six overdoses where naloxone was not used. Where naloxone was used, all 12
      resulted in successful reversal. CONCLUSIONS: With overdose management training,
      opiate users can be trained to execute appropriate actions to assist the
      successful reversal of potentially fatal overdose. Wider provision may reduce
      drug-related deaths further. Future studies should examine whether public policy
      of wider overdose management training and naloxone provision could reduce the
      extent of opiate overdose fatalities, particularly at times of recognized
      increased risk.

PMID- 18821876
TI  - Case for peer naloxone further strengthened.

PMID- 18821877
TI  - Smokers' use of nicotine replacement therapy for reasons other than stopping
      smoking: findings from the ITC Four Country Survey.
AB  - AIMS: To measure the prevalence and correlates of nicotine replacement therapy
      (NRT) use for reasons other than quitting smoking among smokers in four
      countries. DESIGN AND SETTING: Population-based, cross-sectional telephone survey
      with nationally representative samples of adult smokers in Canada, the United
      States, the United Kingdom and Australia, conducted in 2005. PARTICIPANTS: A
      total of 6532 adult daily smokers in Canada (n = 1660), the United States (n =
      1664), the United Kingdom (n = 1617) and Australia (n = 1591). MEASUREMENTS:
      Survey questions included demographics, smoking behaviour, use of NRT and reasons
      for NRT use, as well as access and availability of NRT. FINDINGS: Approximately
      17% of smokers surveyed had used NRT in the past year. Among NRT users,
      approximately one-third used NRT for a reason other than quitting smoking,
      including temporary abstinence or reducing the number of cigarettes smoked. The
      prevalence of non-standard NRT use was remarkably consistent across countries.
      Using NRT for reasons other than quitting was associated with higher education
      level, heavier smoking, having no quit intentions, having no past-year quit
      attempts, the type of NRT product used and accessing NRT without a prescription.
      CONCLUSIONS: The use of NRT for purposes other than quitting smoking is fairly
      common and may help to explain the difficulty in detecting significant quitting
      benefits associated with NRT use in population studies. Tobacco control policies,
      including the accessibility of NRT, may have important implications for patterns
      of NRT use.

PMID- 18821878
TI  - Significance of off-label use of NRT.

PMID- 18821879
TI  - Longitudinal study of parental movie restriction on teen smoking and drinking in
      Germany.
AB  - AIMS: To determine if adolescents who report that their parents restrict viewing
      movies based on rating have a lower risk of trying smoking and drinking alcohol
      in the future. DESIGN: Prospective observational study. A cohort of 2110 German
      adolescents younger than 15 years who had never smoked or drunk alcohol at
      baseline were surveyed 12-13 months later to determine smoking and binge drinking
      initiation. Risk of substance use was assessed as a function of parental
      restriction on viewing FSK-16 movies (movies that only those aged 16 years and
      over would be allowed to see in theaters). FINDINGS: The percentage of students
      who tried smoking was 16.3%, 10.9% initiated binge drinking and 5.0% used both
      substances during the follow-up period. There was a significant effect of
      parental movie restriction on each substance use outcome measure after
      controlling for covariates. Compared with adolescents whose parents never allowed
      them to view FSK-16 movies, the adjusted relative risk [(RR) (95% confidence
      interval (CI)] for use of both substances were 1.64 (1.05-2.58) for adolescents
      allowed to view them once in a while, 2.30 (1.53-3.45) for sometimes and 2.92
      (1.83-4.67) for all the time. FSK-16 restrictions were associated with lower
      viewership of all classes of movies, but especially FSK-16/18 movies; in
      addition, FSK-16 restrictions were associated with substantially lower exposure
      to movie depiction of tobacco and alcohol use, suggesting a mediational mechanism
      for the association. CONCLUSIONS: Among young adolescents, parental restriction
      from viewing movies rated for older adolescents/adults decreases the risk of
      substance use in the future.

PMID- 18821881
TI  - Science, pseudoscience and the need for practical knowledge.

PMID- 18821880
TI  - Genetic and environmental contributions to the diversity of substances used in
      adolescent twins: a longitudinal study of age and sex effects.
AB  - AIMS: To determine how genetic and environmental contributions affecting the
      number of psychoactive substances used varies with age and gender over the course
      of adolescence. DESIGN: Estimates of genetic, shared environmental and non-shared
      environmental contributions to total variance in diversity of substances used at
      ages 11, 14 and 17 years were obtained by fitting a multivariate behavior genetic
      (Cholesky) model. PARTICIPANTS: A total of 711 male and 675 female twins.
      MEASUREMENTS: Participants reported whether they had used each of 11 substances.
      FINDINGS: The average diversity of substances used increased over time for both
      males and females, and males generally reported a wider diversity of substances
      used than females. Influences of genetic factors increased with age and were
      greater for males than for females at ages 14 and 17 years. Genetic factors
      remained consistent (i.e. highly correlated) across ages for both males and
      females, as did shared environmental influences for males. Non-shared
      environmental factors for both sexes and females' shared environmental factors
      were age-specific. CONCLUSIONS: Regardless of sex, the proportion of variance in
      substances used attributable to genetic factors increases during adolescence,
      although it is greater for males than females at later ages. These findings
      indicate that prevention interventions may be most effective if they target early
      adolescence when environmental factors account for the majority of variance in
      substance use. The high correlation of genetic factors across ages suggests that
      early use may sometimes signal an early expression of a developmentally stable
      genetic predisposition.

PMID- 18821883
TI  - Is alcohol the only cause of alcohol-related mortality?

PMID- 18821885
TI  - Peri-operative i.v. fluids in diabetic patients--don't forget the salt.

PMID- 18821886
TI  - Bed occupancy and incidence of Methicillin-resistant Staphylococcus aureus
      infection in an intensive care unit.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) incidence and workload as
      reflected by daily bed occupancy were assessed retrospectively over a 12-month
      period in a mixed adult ICU. All MRSA positive results were retrieved from the
      Microbiology Department; patients with MRSA were divided into those whose
      admission swabs were positive and those whose specimens subsequently became
      positive. There were 619 admissions, 48 of which had MRSA on admission (7.8%
      incidence) and 16 new MRSA infections in ICU (total incidence 10.3%). The
      frequency of MRSA acquisition was significantly higher on days when more than
      seven beds were occupied (0.0090 vs 0.0059 new acquisitions per patient per day,
      respectively, p = 0.015). In this well staffed but physically small unit local
      routes of infection transmission may be relevant.

PMID- 18821887
TI  - High dependency care in an obstetric setting in the UK.
AB  - Our objective was to establish the utilisation and pattern of high dependency
      care in a tertiary referral obstetric unit. Data of pregnant or recently pregnant
      women admitted to the obstetric high dependency unit from 1984 to 2007 were
      included to evaluate the admission rate. Four years' information of an ongoing
      prospective audit was collated to identify the indications for admission,
      maternal monitoring, transfers to intensive care unit, and location of the baby.
      The overall high dependency unit admission rate is 2.67%, but increased to 5.01%
      in the most recent 4 years. Massive obstetric haemorrhage is now the most common
      reason for admission. Invasive monitoring was undertaken in 30% of women. Two
      thirds of neonates (66.3%) stayed with their critically ill mothers in the high
      dependency unit. Transfer to the intensive care unit was needed in 1.4 per 1000
      deliveries conducted. We conclude that obstetric high dependency care provides
      holistic care from midwives, obstetricians and anaesthetists while retaining the
      opportunity of early bonding with babies for critically ill mothers.

PMID- 18821888
TI  - Evaluation of pelvic wedge for gynaecological laparoscopy.
AB  - Seventy-eight ASA 1 and 2 women scheduled for elective diagnostic laparoscopy
      under general anaesthesia were randomly allocated into two groups. Patients were
      either positioned with a 20 degrees Trendelenberg tilt (group T) or with a wedge
      placed under the pelvis (group W). A standard general anaesthetic technique was
      used in all patients. The endoscopic view of pelvic organs was graded on a four
      point scale by the operating surgeon. Heart rate (HR), mean arterial pressure
      (MAP), S(p)O(2), and peak airway pressure (Paw) were continuously measured.
      Significantly more patients (77%) in group W had grade 1 view (clear view of
      pelvic organs without additional manoeuvres) when compared with group T (46%).
      Mean Paw increased significantly in group T when compared with group W. The use
      of a pelvic wedge provides a better view of pelvic viscera than 20 degrees
      Trendelenberg tilt during gynaecological laparoscopy.

PMID- 18821889
TI  - 'Thoracic epidural anaesthesia--first do no harm'.

PMID- 18821891
TI  - Epidural analgesia: the need for more evidence.

PMID- 18821892
TI  - Peribulbar block or topical application of local anaesthesia combined for
      paediatric strabismus surgery.

PMID- 18821895
TI  - Monitoring during sedation--the setting is all.

PMID- 18821896
TI  - Comments on a case report of Angelman syndrome anaesthesia.

PMID- 18821898
TI  - A survey of local opinion of NICE guidance on the use of ultrasound in the
      insertion of epidural catheters.

PMID- 18821899
TI  - Oxygen pipeline aneurysm.

PMID- 18821900
TI  - Fixing reinforced tracheal tubes...a surprisingly complex problem.

PMID- 18821901
TI  - Apparent decline in published anaesthetic articles.

PMID- 18821902
TI  - Oral submucous fibrosis and restricted mouth opening.

PMID- 18821903
TI  - Spinal anaesthesia in older children in the United Kingdom: personal experience.

PMID- 18821905
TI  - Dose of lipid emulsion in obstetric anaesthesia in the UK.

PMID- 18821906
TI  - Monitoring central venous pressure: a survey of British intensive care units.

PMID- 18821907
TI  - Thoracic outlet obstruction during neurosurgical positioning.

PMID- 18821909
TI  - Systolic anterior motion of the mitral valve leaflet leading to haemodynamic
      compromise.

PMID- 18821910
TI  - Persistent pain relief following epidural analgesia for cancer pain.

PMID- 18821920
TI  - Self preservation or salvage?

PMID- 18821923
TI  - Artificial neural network: is it free of problems?

PMID- 18821925
TI  - How should patients with an overactive bladder manipulate their fluid intake?

PMID- 18821926
TI  - Millin retropubic prostatectomy.

PMID- 18821930
TI  - Global health inequalities and breast cancer: an impending public health problem
      for developing countries.
AB  - The aim of the study was to provide information on the global health inequality
      pattern produced by the increasing incidence of breast cancer and its
      relationship with the health expenditure of developing countries with emphasis on
      sub-Saharan Africa. It examines the difference between the health expenditure of
      developed and developing countries, and how this affects breast cancer incidence
      and mortality. The data collected from the World Health Organization and World
      Bank were examined, using bivariate analysis, through scatter-plots and Pearson's
      product moment correlation coefficient. Multivariate analysis was carried out by
      multiple regression analysis. National income, health expenditure affects breast
      cancer incidence, particularly between the developed and developing countries.
      However, these factors do not adequately explain variations in mortality rates.
      The study reveals the risk posed to developing countries to solving the present
      and predicted burden of breast cancer, currently characterized by late
      presentation, inadequate health care systems, and high mortality. Findings from
      this study contribute to the knowledge of the burden of disease in developing
      countries, especially sub-Saharan Africa, and how that is related to
      globalization and health inequalities.

PMID- 18821932
TI  - Nipple-sparing mastectomy: lessons from ex vivo procedures.
AB  - Moderate size series have reported successful nipple-sparing mastectomy using a
      variety of surgical techniques. This study aimed to understand which aspects of
      these techniques are safe, necessary, and successful. Eight skin-sacrificing
      mastectomy specimens were used as ex vivo models of nipple-sparing mastectomy.
      After inking the resection margins of the specimen, the skin ellipse was elevated
      in the subcutaneous plane using a scalpel. The retroareolar breast tissue was
      taken as a margin specimen. The nipple was inverted and the nipple core removed.
      The hollowed-out nipple remnant (which would have remained with the patient in a
      true nipple-sparing mastectomy) was submitted for confirmatory histopathologic
      analysis. Precise identification of the duct margin directly beneath the nipple
      proved difficult once the duct bundle had been divided. Successful retroareolar
      margin identification was achieved by grasping the duct bundle with atraumatic
      forceps as soon as it became exposed. A cut made below and above the forceps
      resulted in a full cross-section of the duct bundle. Nipple core tissue was
      difficult to excise in one piece and cannot be oriented, thus complete evaluation
      of the specimen required examination of multiple levels. Histologic artifacts
      caused by freezing may be present in frozen sections of nipple core and
      retroareolar margin specimens; the impact of such changes must be considered when
      developing institutional protocols for this procedure. Evaluation of the hollowed
      out nipple revealed that the inverted nipple must be substantially thinned to
      remove all ducts. Modification of technique resulted in more complete excision of
      duct tissue. This series of ex vivo procedures provides information that can be
      used to modify surgical and pathologic techniques for nipple-sparing mastectomy.
      When performing nipple-sparing mastectomy for breast cancer, these measures may
      be advisable as complements to careful patient selection.

PMID- 18821931
TI  - Role of endocrine responsiveness and HER2/neu overexpression in inflammatory
      breast cancer treated with multimodality preoperative therapy.
AB  - We analyzed the role of endocrine responsiveness and HER2/neu overexpression in
      inflammatory breast cancer treated with multimodality preoperative therapy.
      Thirty-eight patients (estrogen receptor [ER] and/or progesterone receptor [PgR]
      >or=10% of the cells 21, premenopausal 14, Ki-67 expression >or=20% of the cells
      30, HER2/neu overexpressed 11) were treated with six courses of epirubicin,
      cisplatin and fluorouracil (FU) as continuous infusion, perioperative FU as
      continuous infusion, mastectomy and loco-regional radiotherapy. In endocrine
      responsive patients, endocrine treatment (letrozole, either alone or if
      premenopausal with triptorelin) was given preoperatively and as adjuvant
      treatment. There were 32 objective responders (84.2%; 95% CI 70.0-94.6%), three
      of whom had pathologic complete remission. At the multivariate analysis disease
      free survival was significantly worse in patients with ER and PgR absent tumors
      compared with the positive expression cohort (hazards ratio [HR]: 5.91; 95% CI
      1.69-20.7; p = 0.005), in particular if HER2/neu overexpression was detected (HR:
      16.5; 95% CI 4.24-64.5; p < 0.0001). New multimodality and targeted strategies
      should be explored in endocrine nonresponsive breast cancer.

PMID- 18821933
TI  - Efficiency of Core Biopsy for BI-RADS-5 Breast Lesions.
AB  - Stereotactic biopsy has proven more cost effective for biopsy of lesions
      associated with moderately suspicious mammograms. Data regarding selection of
      stereotactic biopsy (CORE) instead of excisional biopsy (EB) as the first
      diagnostic procedure in patients with nonpalpable breast lesions and highest
      suspicion breast imaging-reporting and data system (BI-RADS)-5 mammograms are
      sparse. Records from a regional health system radiology database were screened
      for mammograms associated with image-guided biopsy. A total of 182 nonpalpable BI
      RADS-5 lesions were sampled in 178 patients over 5 years, using CORE or EB.
      Initial surgical margins, number of surgeries, time from initial procedure to
      last related surgical procedure, and hospital and professional charges for
      related admissions were compared using chi-squared, t-test, and Wilcoxon Mann
      Whitney tests. A total of 108 CORE and 74 EB were performed as the first
      diagnostic procedure. Invasive or in situ carcinoma was diagnosed in 156 (86%) of
      all biopsies, 95 in CORE and 61 in EB groups. Negative margins of the first
      surgical procedure were more frequent in CORE (n = 70, 74%) versus EB (n = 17,
      28%), p < 0.05. Use of CORE was associated with fewer total surgical procedures
      per lesion (1.29 +/- 0.05 versus 1.8 +/- 0.05, p < 0.05). Time of initial
      diagnostic procedure to final treatment did not vary significantly according to
      group (27 +/- 2 days versus 22 +/- 2 days, CORE versus EB). Mean charges
      including the diagnostic procedure and all subsequent surgeries were not
      different between CORE and EB groups ($10,500 +/- 300 versus $11,500 +/- 500, p =
      0.08). Use of CORE as the first procedure in patients with highly suspicious
      mammograms is associated with improved pathologic margins and need for fewer
      surgical procedures than EB, and should be considered the preferred initial
      diagnostic approach.

PMID- 18821934
TI  - Computer vision techniques for breast tumor ultrasound analysis.
AB  - In this paper, we present a new approach to the segmentation and analysis of
      solid breast nodules in ultrasonography. We have applied computer vision
      techniques to segment the nodules and analyze a series of diagnostic criteria
      which can help discriminate malignant and benignant tumors. The segmentation is
      carried out in a semiautomatic way, whereas the analysis of the diagnostic
      criteria involves several computational methods. The techniques which we propose
      have provided quite satisfactory results and show the usefulness of image
      processing in the diagnosis through medical imaging.

PMID- 18821935
TI  - A case of heterogeneous breast cancer with clonally expanded T-Cells in the HER2+
      and metastasis of the HER2- tumor cells.
AB  - We report a case of an invasive ductal breast carcinoma with significant
      heterogeneity: a HER-2+ tumor component was densely infiltrated by T-cells,
      whereas the HER2- tumor component, including two axillary lymph node metastases,
      showed much fewer tumor infiltrating lymphocytes. Array comparative genomic
      hybridization of dissected tumor cells from both components revealed many shared
      chromosomal aberrations but also unique alterations of the HER2+ tumor cell
      population besides HER2 amplification. We found a clonally dominated T-cell
      receptor rearrangement of the tumor infiltrating lymphocytes in the HER2+, but
      not in the HER2- tumor component. Thus, in this case HER2 overexpression is
      associated with a marked infiltration by T-cells suggesting a specific T-cell
      response against the HER2+ tumor cell population.

PMID- 18821937
TI  - Dermatitis artefacta of the breast: a diagnostic dilemma.

PMID- 18821936
TI  - Choroidal metastasis as first manifestation of systemic recurrence of breast
      cancer.

PMID- 18821938
TI  - Pure tubular breast carcinoma: a 34 year study of outcomes.

PMID- 18821940
TI  - Higher constitutive IL15R alpha expression and lower IL-15 response threshold in
      coeliac disease patients.
AB  - The IL-15 triggering effect of gliadin is not exclusive to coeliac disease (CD)
      patients, whereas the secondary response is CD specific. We have studied the
      expression of the IL-15 receptor, and the IL-15 response upon stimulation, in non
      CD and CD patients, and the possible existence of a lower immunological threshold
      in the latter. Forty-two CD patients (20 on a gluten-containing diet, GCD, and 22
      on gluten-free diet, GFD) and 24 non-CD healthy individuals were studied. IL15R
      alpha mRNA expression, and tissue characterization, were assayed in the duodenum.
      Biopsies from six CD patients on GFD and 10 non-CD individuals were studied in
      vitro using organ culture in basal conditions, as well as after IL-15 stimulation
      discarding basal IL-15 production. Secretion of immune mediators was measured in
      the culture supernatants. IL15R alpha mRNA expression was increased in CD
      patients, as compared with non-CD controls (on GFD P = 0.0334, on GCD P = 0.0062,
      respectively), and confirmed also by immunofluorescence. No differences were
      found between CD patients on GFD and on GCD. After in vitro IL-15 stimulation,
      IL15R alpha expression was only triggered in non-CD controls (P = 0.0313), though
      it remained increased in CD patients. Moreover, IL-15 induced a more intense
      immunological response in CD patients after triggering the production of both
      nitrites and IFN gamma (P = 0.0313, P = 0.0313, respectively). Gliadin-induced
      IL15 has a lower response threshold in CD patients, leading to the production of
      other immune mediators and the development of the intestinal lesion, and thus
      magnifying its effects within the CD intestine.

PMID- 18821941
TI  - Do cytokines have any role in Wilson's disease?
AB  - The aim of this study was to determine the serum cytokine levels in patients with
      Wilson's disease (WD) and correlate with phenotype, therapeutic status and
      laboratory data. In this cross-sectional study, the serum levels of cytokines
      were estimated in 34 patients (M : F, 23 : 11; drug-naive, 11) with WD (mean age:
      13.8 +/- 8.6 and 19.6 +/- 9.03 years) and compared with 30 controls. The
      following serum cytokines were analysed using enzyme-linked immunosorbent assay:
      (i) tumour necrosis factor (TNF)-alpha, (ii) interferon (IFN)-gamma, (iii)
      interleukin (IL)-2, (iv) IL-6 and (v) IL-4. Serum TNF-alpha (P < 0.001), IFN
      gamma (P = 0.005) and IL-6 (P < 0.001) were detectable in WD compared with
      controls. However, serum level elevation of IL-4 (P = 0.49) and IL-2 (P = 0.11),
      although detectable compared with controls, was statistically insignificant. The
      disease severity and therapeutic status did not affect the cytokines. Presence of
      anaemia, leucopenia, thrombocytopenia, pancytopenia and hepatic dysfunction did
      not influence cytokine levels. There was a significant negative correlation
      between IL-6 and ceruloplasmin (P = 0.04) and anti-inflammatory cytokines (IL-4)
      and copper level (P = 0.01). Serum cytokines, both proinflammatory and anti
      inflammatory subtypes, were elevated significantly in patients with WD. Further
      studies would establish their role in its pathogenesis.

PMID- 18821944
TI  - Breast fine needle aspiration: a way forward for a threatened art.

PMID- 18821942
TI  - Regulatory T cells in human immunodeficiency virus-infected patients are elevated
      and independent of immunological and virological status, as well as initiation of
      highly active anti-retroviral therapy.
AB  - Infection with human immunodeficiency virus (HIV) causes a dysregulation of the
      immune system. This is caused by HIV-specific as well as non-specific mechanisms
      and has not been explained fully. In particular, knowledge is lacking about the
      potential role of host-mediated immunosuppressive mechanisms. During recent years
      it has become evident that a subpopulation of T cells [T regulatory (T(regs))]
      play a major role in sustaining tolerance to self-antigens. To investigate the
      influence of initiation of highly active anti-retroviral therapy (HAART) on the
      T(reg) level in HIV-infected patients we have conducted a prospective study
      enrolling treatment-naive HIV-infected patients just prior to starting treatment
      with HAART, measuring levels of T(regs) by flow cytometry and mRNA expression of
      forkhead box P3 (FoxP3) at weeks 0, 4, 12 and 24 of treatment. In this
      prospective study neither the percentage of CD4(+)CD25(high+) nor the expression
      of FoxP3 changed significantly during 24 weeks of HAART. Furthermore, HIV
      patients have higher T(regs) measured as percentages of CD4(+)CD25(high+) cells
      paralleled by higher levels of FoxP3 compared with healthy controls. The elevated
      level of T(regs) was found to be independent of both immunological and
      virological status, indicating that initiation of HAART has minor effects on the
      T(reg) level in HIV-infected patients.

PMID- 18821947
TI  - Replantation of an immature permanent central incisor following pre-eruptive
      traumatic avulsion.
AB  - Tooth avulsion represents 0.5-16% of traumatic injuries. Avulsion of a pre
      eruptive left permanent maxillary incisor in a 6-year-old boy is presented. The
      immature tooth was replanted after rinsing with saline following 10 min dry extra
      oral time. This case report describes treatment and a 2-year follow-up of the
      tooth. During the follow-up period, continuation of root development, pulp
      revascularization, and irregular dentin formation were demonstrated. The tooth is
      vital, functional, and esthetic. To the best of our knowledge, no such case of
      replantation of a pre-eruptive tooth has been reported previously.

PMID- 18821945
TI  - The role of breast FNAC in diagnosis and clinical management: a survey of current
      practice.
AB  - Most participating countries have now adopted a triple assessment approach, i.e.
      clinical,imaging and pathology, to breast diagnosis, with FNAC as the first-line
      pathological investigation in both screening and symptomatic populations, with
      the exception of microcalcifications. Pathologists specialized in cytopathology
      are best qualified to collect and interpret FNAC samples, but this is not always
      possible or practical. Radiologists involved in breast imaging should ensure that
      they have the necessary skills to carry out FNAC under all forms of image
      guidance. Best results are achieved by a combination of both techniques, as shown
      in the image-guided FNAC in the presence of the cytopathologist. The majority of
      European countries use similar reporting systems for breast FNAC (C1-C5), in
      keeping with European Guidelines for Quality Assurance in Breast Cancer Screening
      and Diagnosis, although some still prefer descriptive reporting only. When triple
      assessment is concordant, final treatment may proceed on the basis of FNAC,
      without a tissue biopsy. ER and PR assessment can be done safely on FNAC
      material. However, not all institutions may have expertise in doing this. HER-2
      protein expression on direct cytological preparations is insufficiently reliable
      for clinical use, although its use for FISH is possible, if expertise is
      available. The majority of participants practise a degree of one-stop diagnosis
      with a cytopathologist present in the out-patient clinic. Formal recognition of
      the importance of the time spent outside the laboratory, both for cytopathologist
      and cytotechnologist, is necessary in order to ensure appropriate resourcing. The
      use of core biopsy (CB) has increased, although not always for evidence-based
      reasons. CB and FNAC are not mutually exclusive. FNAC should be used in diagnosis
      of benign, symptomatic lesions and CB in microcalcifications, suspicious FNAC
      findings and malignancies where radiology cannot guarantee stromal invasion.

PMID- 18821948
TI  - Arrest of root formation in a permanent maxillary central incisor subsequent to
      trauma and pulp necrosis to the primary predecessor.
AB  - This paper reports a case in which a previous traumatic injury at the age of 2
      and pulp necrosis to a primary incisor resulted in a rare injury to the permanent
      successor tooth. The radiographic examination at the age of 9 showed the arrest
      of root formation of the permanent maxillary right central incisor, which did not
      erupt. Tooth 11 was extracted and a functional removable space maintainer was
      prepared. At the age of 17, the patient received an anterior fixed prosthesis for
      re-establishment of the esthetics, phonetics and deglutition.

PMID- 18821949
TI  - A successful treatment of vertical root fracture: a case report and 4-year follow
      up.
AB  - This case report describes a successful treatment of vertically fractured tooth
      which was reconstructed with a self-etching dual-cured adhesive resin cement and
      intentionally replanted without using rotation in conjunction with a bio
      absorbable barrier membrane. At a follow-up consultation 4 years later, the tooth
      was asymptomatic, and attachment gain and bone regeneration were observed. In
      addition, no ankylosis was detected clinically or radiographically.

PMID- 18821950
TI  - Evidence-based dental traumatology.

PMID- 18821951
TI  - Efficacy of enamel matrix derivatives (Emdogain) in treatment of replanted teeth-
      a systematic review based on animal studies.
AB  - The objective of the current systematic review was to evaluate the efficacy of
      enamel matrix derivative (EMD) (Emdogain) on healing of replanted or
      autotransplanted permanent teeth. A review of the published literature [search
      term: (Emdogain OR enamel matrix derivative OR enamel matrix protein] AND
      [avulsion OR replantation OR autotransplantation)] was conducted by two
      independent investigators according to defined selection criteria. For data
      extraction of the identified animal studies, the following histomorphometric
      findings were considered: (i) healed PDL, (ii) surface resorption, (iii)
      inflammatory resorption and (iv) replacement resorption. The heterogeneity of
      data collection and the small amount of identified publications did not allow for
      statistical analysis. Four controlled trials (CT) conducted in animals, but no
      randomized controlled trials (RCT) or clinical controlled trials (CCT) could be
      received from the systematic search. From the selected studies, two CT gave
      evidence of EMD treatment to be effective in inducing healing of replanted teeth,
      while one CT found no differences between EMD treated teeth and controls.
      Finally, one CT compared EMD and sodium fluoride application, but revealed no
      differences between the treatments. The data of controlled trials available are
      limited and conflicting. No firm conclusion regarding the efficacy of EMD
      application on healing of replanted or autotransplanted permanent teeth can be
      drawn because of lack of RCT and CCT.

PMID- 18821952
TI  - Root fractures in children and adolescents: diagnostic considerations.
AB  - The objectives of this study were to (i) characterize epidemiologic trends in
      anterior permanent tooth trauma in a sample of children and adolescents (ii)
      examine the relationship of crown fractures (CF) and concomitant root fractures
      (RF) to determine if CFs are protective against RFs and (iii) examine the
      radiographic evidence of RFs to determine the value of obtaining three vertical
      periapical radiographic projections. This was an 8-year cross-sectional study of
      patients aged 6-18 with anterior permanent tooth trauma. We examined cases
      involving maxillary central/lateral incisors for which three clearly diagnostic
      periapical radiographs were obtained during the initial emergency visit. Two
      trained and calibrated dentists served as expert examiners for the radiographic
      assessments. Kappa statistics were used to determine reliability. Tests for
      association of concomitant crown and root fractures were performed using
      Likelihood Ratio Chi-Square tests. The final sample included 185 teeth in 114
      children. Our demographic and epidemiologic findings were comparable to those of
      previous studies. Experts reached this consensus: 22 RFs were detected, 9.6%
      (eight out of 83) teeth exhibited root fractures when no CFs was documented, and
      13.7% (14 out of 102) teeth had both CFs and RFs as separate entities. Good
      examiner reliability was reached confirming the presence of RFs (Kappa = 0.81).
      The association of concomitant RFs and CFs was odds ratio = 1.97 (P = 0.052). CFs
      were not protective against RFs; indeed, teeth with CFs were twice as likely to
      have an RF as those without CFs. As the number of radiographic projections
      increased, RFs were identified more often; however, our data suggest that there
      is no reason to suspect a complete RF in preteen children unless the root
      exhibits clinical signs such as luxation or severe mobility. This study provides
      solid evidence to support obtaining multiple radiographic projections at
      different vertical angulations to rule out RFs in children and adolescents when
      RFs are suspected.

PMID- 18821953
TI  - Periodontal healing of replanted dog teeth stored in milk and egg albumen.
AB  - The type of storage medium used to store avulsed teeth prior to replantation has
      been shown to be a decisive factor in periodontal ligament (PDL) healing. The aim
      of the present study was to investigate the effect of storage medium on
      periodontal healing. Thirty teeth from three dogs were endodontically treated to
      prevent subsequent inflammatory root resorption. The teeth were atraumatically
      extracted and randomly stored in milk or egg albumen for 3, 6 and 10 h at 4
      degrees C. All teeth were splinted for 1 weeks after replanting. After 2 months
      animals were sacrificed using vital perfusion-fixation and teeth were
      histologically prepared and evaluated following Andreasen's method. It was found
      that teeth stored in egg albumen for 6 and 10 h had significantly higher incident
      of PDL healing than those treated with milk for the same period (P < 0.05). . The
      highest incidence of PDL healing was observed in teeth stored in egg albumen for
      6 h. The least surface resorption was also evident in this group (P < 0.05). The
      result of this study shows that egg albumen is an excellent storage media for up
      to 10 h considering its likely availability at most accident sites.

PMID- 18821954
TI  - The effect of a leaflet given to parents for first aid measures after tooth
      avulsion.
AB  - The aims of this study were to evaluate knowledge level among parents regarding
      tooth avulsion and replantation and to evaluate a simple leaflet as an
      information tool to enhance this knowledge. One Hundred and fifty parents in a
      primary school in Kuwait City participated in the study. Half of the parents
      received a leaflet with basic first aid message regarding what to do in case of
      tooth avulsion. One week after reading the leaflet, the parents who had received
      the leaflet were evaluated by using a questionnaire. The other half of the
      parents who had not seen the leaflet served as control. The level of knowledge
      was measured in the following categories: General knowledge of tooth avulsion,
      knowledge of replantation and primary vs permanent teeth, knowledge of how to
      clean an avulsed tooth, knowledge of extra-oral time, knowledge of storage
      methods and storage media. By scoring the knowledge, the level of knowledge was
      calculated. The results showed that knowledge level was low among Kuwaiti
      parents. Improvement was seen in all categories of knowledge as a result of
      reading the leaflet. A simple leaflet can be a valuable tool to convey important
      basic information and enhance knowledge of tooth avulsion and how parents should
      act in such a situation, although there are limitations in conveying the message
      for a complete understanding. Measuring the knowledge by scoring can give
      valuable feedback in developing various educational tools.

PMID- 18821955
TI  - Dental injuries in mountain biking--a survey in Switzerland, Austria, Germany and
      Italy.
AB  - Mountain biking is considered an extreme sport, causing not only head and neck
      injuries, but also injuries to every part of the body. Using standardised
      interview, the aim of this work was to survey the frequency of dental injuries in
      mountain biking, as well as the behaviour of athletes after experiencing dental
      trauma, depending on their intensity level. Furthermore, habits of wearing
      helmets and mouthguards as well as knowledge about the tooth rescue kit were
      investigated. A total of 423 male mountain bikers from Germany, Italy, Austria
      and Switzerland were surveyed for this study, including 50 juniors from
      Switzerland. 27 athletes (5.7%) had endured tooth accidents in mountain biking.
      Only 246 (52%) were aware of the fact that avulsed teeth can be replanted, and
      only 30 individuals knew about the tooth rescue kit (6.3%). 71.9% (n=340) were
      familiar with mouthguards; however, only 21 individuals (4.4%) used mouthguards
      while mountain biking. The results show that where mountain biking is concerned,
      more information about prevention is required.

PMID- 18821956
TI  - Attitude of Pilsen primary school teachers in dental traumas.
AB  - Dental injuries are rather common during sport activities and at schools where
      children spend most of their time every day. The purpose of this study was to
      evaluate the knowledge of primary school teachers in Pilsen, Czech Republic, of
      how to provide first aid in cases of one of the most serious dental injuries, the
      tooth avulsion. To this end, a questionnaire which contained nine questions about
      avulsion of permanent teeth was prepared. The questionnaires were distributed in
      nine primary schools in Pilsen where almost 300 teachers are employed. Seventy
      four percent of the teachers replied. Sixty-eight percent had never received any
      information about providing first aid in cases of dental injuries and 81% would
      place the avulsed tooth in a dry handkerchief until the transfer of the patient
      to dentist. Prevention of tooth injuries is very important, as they may result
      even in tooth loss. This demands an effort to properly inform and educate sport
      trainers and primary school teachers about providing first aid in dental trauma
      situations; this effort should be intensive and continuous.

PMID- 18821957
TI  - The relationship between sports activities and permanent incisor crown fractures
      in a group of school children aged 7-9 and 11-13 in Ankara, Turkey.
AB  - The objective of the study was to determine the distribution, aetiology of the
      crown fractures of permanent anterior teeth in children aged 7-9 and 11-13 years
      and to identify the role of participation in sports associated with crown
      fractures. The study population comprised 2570 students from 10 primary schools
      randomly selected from five municipalities in Ankara, Turkey. Two paediatric
      dentists examined all permanent maxillary and mandibular incisors for evidence of
      fracture and completed a standardized examination form to obtain information on
      the age, gender, severity of incisor injury and frequency and type of sports
      participation for each child, as well as whether or not children used mouthguards
      during sports activities. Chi-square and z-tests were used to determine
      differences. A total of 191 (7.43%) of the 2570 subjects examined were affected
      by dental trauma. The proportion of fractured incisors was significantly higher
      in males than in females among older children (P < 0.01). Out of a total of 222
      fractured teeth, 84% involved the maxillary central incisors. Bicycling caused
      significantly higher rates of crown fractures than other types of sports (P <
      0.05). The percentage of incisal fractures caused by sports-related accidents was
      14.14%. The number of children interested in sports is high, and the sports
      chosen are generally contact sports. The high rate (14.14%) of crown injuries
      caused by sports activities supports these findings.

PMID- 18821958
TI  - Diagnostic of tooth fractures with the Vistascan system.
AB  - Compared with conventional films digital radiography allows a wide range of
      exposure and scanner settings. The aim of this study was to investigate the
      diagnostic accuracy of the evaluation of tooth fractures depending on variations
      of exposure dose, scanner settings and surrounding tissues. Extracted human teeth
      were exposed separately and in a pig bone phantom before and after artificial
      fracture at 70 kV (Gendex Oralix DC) and three exposure settings using the
      Vistascan System I at three different resolution settings. Five dental observers
      evaluated 432 radiographs of 12 adequately fractured teeth under randomized
      conditions for the existence of a tooth fracture on a five-point scale. The
      highest value of true ratings (76.7%) with pig bone vicinity was achieved at 56
      micro Gy (160 ms) and 20 lp mm(-1), followed by 71.7% at 27 micro Gy (80 ms) and
      20 lp mm(-1). The worst diagnostic accuracy of 56.7% true ratings resulted from 6
      micro Gy (20 ms) and 10 lp mm(-1). With radiographs of teeth in empty
      surroundings the rate of true decisions was in some cases significantly higher.
      For the diagnostics of tooth fractures with the Vistascan System I the diagnostic
      value seems to depend on, besides radiographic projection, the scanner resolution
      setting, the surrounding tissues and the exposure dose.

PMID- 18821959
TI  - pH changes after manual or ultrasonic instrumentation and smear layer removal
      with EDTA or ultrasonic.
AB  - The purpose of the present study was to evaluate the influence of instrumentation
      techniques associated with the smear layer removal, in the pH changes of the root
      surface. Thirty mandibular humans premolars were divided into three groups: Group
      I - instrumentation by Ohio technique and final cleaning with EDTA (3 minutes);
      Group II - instrumentation by Ohio technique and final cleaning with ultrasonic
      (1 minute); Group III - instrumentation by the ultrasonic technique and final
      cleaning with ultrasonic (1 minute). The pH was measured in the cavities prepared
      in the cervical, middle and apical thirds of the lateral wall of each root. The
      teeth were evaluated at the initiation of the experiment, and 3, 7, 14, 21, 30
      days after of the intracanal dressing of the calcium hydroxide with camphorated p
      monochlorophenol (Calen/PMCC). All the groups presented increasing pH values;
      group III presented the highest average pH, followed by groups II and I; the
      values for the apical third were lower than those of the middle and cervical
      thirds (anova and Tukey test). The results showed that the biomechanical
      preparation by the ultrasonic technique and smear layer removal with ultrasonic
      showing the highest diffusion of the calcium and hydroxyl ions from the
      intracanal dressing (P < 0.05).

PMID- 18821960
TI  - Rapidly progressive internal root resorption: a case report.
AB  - The etiology of internal root resorption is not fully understandable, trauma and
      chronic pulpitis are considered the main risk factors. Usually the process is
      asymptomatic and diagnosed upon routine radiographic examination. This case
      report presents a rapid progression of internal resorption related directly to
      traumatic injury. A 16-year-old female arrived at the emergency room after a mild
      extrusion of the mandibular incisors. The initial treatment included
      repositioning and splinting of the teeth. Radiographs performed at repositioning
      and splinting demonstrated normal configuration of the incisor's roots. Ten
      months later progressive internal resorption of the left mandibular first incisor
      was diagnosed. While treating this tooth similar process was detected in the
      right mandibular second incisor and in the mandibular left second incisor. The
      lower right first incisor reacted inconsistently to vitality test. As a result of
      the severe and rapidly progressive nature of the process, root canal treatments
      were performed in all lower incisors. The follow-up radiographs demonstrate
      arrest of the internal resorption process.

PMID- 18821961
TI  - An unusual lateral luxation of an upper incisor owing to long-term boxing without
      protection.
AB  - This case report describes a lateral luxation of an upper incisor in a 19-year
      old non-professional boxer. The tooth displacement gradually worsened over
      several months because the boxer received repeated blows to the head without
      using a mouthguard. Being a chronic dental trauma, rather than an acute lateral
      luxation, this case had several unique features: the labial plate of the alveolar
      bone was penetrated, the root apex was free in the vestibulum, the tooth was
      mobile (second degree) and radiographs revealed bone resorption. This case
      emphasized the need for a mouthguard to be used even with amateur boxing. The
      dental practitioner should educate his sportsmen-patients of the risk of sport
      related dental trauma and the benefit of a mouthguard.

PMID- 18821962
TI  - Partial replacement of the dentin-pulp complex by periodontal supporting tissues
      in a traumatically intruded primary maxillary incisor.
AB  - This paper describes a case of a 9-year-old patient who presented a completely
      intruded primary maxillary incisor because of a traumatic injury sustained at the
      age of 3 years. After tooth extraction, histological analysis revealed that the
      dentin-pulp complex was partially replaced by cementum, periodontal ligament and
      alveolar bone. No signs of ankylosis were noticed. It is suggested that the lack
      of spontaneous re-eruption of the traumatized primary tooth after 6 years could
      be due to the development of functional periodontal supporting tissues in the
      pulp chamber secondary to the traumatism.

PMID- 18821963
TI  - External multiple invasive cervical resorption with subsequent arrest of the
      resorption.
AB  - A rare, the uncommon, case of multiple invasive cervical resorption (MICR) with
      subsequent arrest of the resorption involving eight teeth of the mandible (tooth
      46 to tooth 32) is presented. This case is noteworthy because of the
      characteristics of its clinical evolution. There have only been a few cases in
      the literature were found presenting involvement of such a large number of teeth.
      Furthermore, no reports on cases of MICR with arrest of the resorption, as
      described in this report, were found.

PMID- 18821964
TI  - Rehabilitation of severely injured anterior teeth in a young patient using
      ceramic and FRC: a clinical report.
AB  - This clinical report describes the indirect restoration of anterior teeth in a
      young patient after a severe dental trauma using all-ceramic coronal posts. Step
      by-step clinical procedures and their rationale are described. The learning
      objective of this case report is to outline the principles for the management of
      traumatic injuries of permanent anterior teeth in young patients to re-establish
      function and provide good esthetic results.

PMID- 18821965
TI  - Mineral trioxide aggregate as an alternative treatment for intruded permanent
      teeth with root resorption and incomplete apex formation.
AB  - A case of extensive crown fracture associated with intrusion of the permanent
      maxillary central incisors in an 8-year-old boy is reported. The treatment of
      both injured teeth included attempts of apexification and arrest of root
      resorption with calcium hydroxide. After 8 months of the trauma, there was no
      calcified barrier formation in the apex. Mineral trioxide aggregate (MTA) was
      then used as a filling material. At 15-month follow up, the teeth were
      asymptomatic and correctly sealed, the external inflammatory root resorption had
      stopped, and the radiolucent image had disappeared, which meant the initial
      healing of the periapical lesion. MTA may be considered as an alternative option
      for the treatment of traumatized and immature permanent teeth.

PMID- 18821966
TI  - Replantation of an avulsed maxillary primary central incisor and management of
      dilaceration as a sequel on the permanent successor.
AB  - This case report outlines the sequel and possible management of a permanent tooth
      traumatized through the predecessor, a maxillary right primary central incisor
      that was avulsed and replanted by a dentist 1 h after the trauma in a 3-year-old
      girl. Three years later, discoloration and fistula were present, so the primary
      tooth was extracted. The patient did not come to the scheduled follow-ups to
      perform a clinical and radiographic control of the succeeding permanent incisor,
      and only returned when she was 10 years old. At that moment, the impaction and
      dilaceration of the maxillary right permanent central incisor were observed
      through radiographic examination. The dilacerated permanent tooth was then
      surgically removed, and an esthetic fixed appliance was constructed with the
      crown of the extracted tooth. Positive psychological influence of the treatment
      on this patient was also observed.

PMID- 18821967
TI  - Use of a crown fragment to establish favorable temporary crown.
AB  - This case describes the esthetic management of a fractured tooth at first visit
      and its subsequent treatments to restore the esthetics and function. Patients
      expect adequate esthetics immediately after the first appointment. In addition,
      they require that esthetics is maintained throughout the definitive treatment
      phase as well. After the use of the fractured crown fragment as a temporary
      crown, a root canal treatment was undertaken in a conventional manner. The
      rehabilitation of the fractured tooth was performed with a post-core-supported
      prosthetic restoration. Examination at 18 months after treatment revealed good
      esthetics and normal function.

PMID- 18821968
TI  - Intraradicular splinting with endodontic instrument of horizontal root fracture-
      case report.
AB  - This case report describes the treatment of a horizontal mid-root-fractured
      incisor with an alternative fixation technique. As a result of clinical signs of
      pulpal necrosis, both the coronal and the apical root fragments were
      endodontically treated and obturated at single visit, and the fragments were
      stabilized internally through insertion of a stainless-steel endodontic file into
      the root canal. Four-year follow-up examination revealed satisfactory clinical
      and radiographic findings with hard tissue repair of the fracture line. This
      technique can be a quick remedy for patients with root-fractured tooth,
      especially for those who cannot make a second visit to the dental clinic.

PMID- 18821969
TI  - Treatment of complex dentoalveolar injury--avulsion and loss of periodontal
      tissue: a case report.
AB  - Dental avulsion is a common and complex injury which affects multiple oral
      tissues. In this case report, a 9-year-old girl patient with two traumatically
      avulsed maxillary central incisors with loss of periodontal tissue was presented.
      Treatment guidelines for avulsed permanent teeth with open apex were carried out.
      Bilateral laterally sliding flap procedure was performed, to repair loss of
      gingival soft tissue. Conventional immobilization was carried out for 6 weeks.
      Five months follow-up of the patient in whom replantation was performed resulted
      in positive sensitivity test, no symptoms of infection, pain or any discomfort
      and good periodontal wound healing. In conclusion, this report presents
      successful replantation and periodontal treatment of a patient with complex
      dentoalveolar injury.

PMID- 18821970
TI  - Avulsion and replacement of the tooth element fractured at the level of the
      middle 1/3: a case report.
AB  - Dental trauma continues to cause loss of teeth, particularly in the anterior
      region of the maxilla. Reimplanting the tooth with the fragment repositioned by
      turning it through 180 degrees presents a conservative treatment option that
      makes it possible to keep a tooth, at first indicated for extraction, functioning
      and with a satisfactory esthetic appearance.

PMID- 18821971
TI  - Two-year follow-up of fractured anterior teeth restored with direct composite
      resin: report of three cases.
AB  - Thirty-five (case 1), 15 (case 2) and 22 (case 3)-year-old female patients
      presented to Yeditepe University Dental Faculty Clinic because of esthetic
      reasons. Fractures of maxillar central incisors including enamel and dentin were
      diagnosed. Beveling with diamond bur was performed in all four cases. Dentin was
      cleaned with tungsten carbid bur. The teeth were etched with 37% phosphoric acid,
      restored with an adhesive system and microhybrid composite. Finishing and
      polishing procedures were performed by discs (Sof-Lex) and burs. Restorations
      were found successful according to modified United States Public Health Service
      (USPHS) criteria after 2 years in terms of retention, color match, marginal
      discoloration, secondary caries, marginal adaptation, and surface texture.

PMID- 18821972
TI  - Re: An occult foreign body aspiration with bronchial anomaly mimicking asthma and
      pneumonia.

PMID- 18821974
TI  - The quest for biofuels fuels genome sequencing.

PMID- 18821977
TI  - The ever-widening spectrum of varicella zoster virus vasculopathy.

PMID- 18821978
TI  - Autoregulation might explain why blood pressure is not associated with haematoma
      enlargement in acute intracerebral haemorrhage.

PMID- 18821979
TI  - Neuroplasticity of edentulous patients with implant-supported full dentures.
AB  - Edentulous patients with implant-supported prostheses report improved tactile
      discriminative capabilities and motor function compared with when they wore
      complete dentures. 'Osseoperception' is defined as the ability to identify
      kinesthetic sensation without the input from periodontal mechanoreceptors. This
      sensation is generated from the temporomandibular joint, masticatory muscle,
      mucosa, and periosteum, and provides sensory and motor information related to
      mandible movements and occlusion. The aim of this study was to analyze the
      cortical plasticity occurring in patients with implant-supported prostheses.
      Twenty edentulous patients with implant-supported full dentures or traditional
      complete dentures were recruited for a clenching task. They were scanned by
      functional magnetic resonance imaging (fMRI), and the data were analyzed using
      the spm99 software package to generate activation brain maps. Increased blood
      oxygen level dependent signals in the primary sensorimotor cortex were found in
      patients with implant-supported fixed dentures. Other activated areas included
      prefrontal cortex, Broca's area, premotor cortex, supplementary motor area,
      superior temporal gyrus, insular, basal ganglion, and hippocampus. We suggest
      that sensory and motor feedback to the central nervous system can be restored by
      implant-supported full dentures. Activation of the primary sensorimotor cortex in
      patients with implant-supported dentures might explain the improved tactile,
      stereognostic ability, and mastication functions, which are more similar to the
      natural dentition.

PMID- 18821980
TI  - Taste deficits after middle ear surgery for otosclerosis: taste somatosensory
      interactions.
AB  - The aim of this study was to evaluate the postoperative consequences of chorda
      tympani reclining during middle ear surgery for otosclerosis. Electrogustometric
      taste thresholds were measured at 11 loci on the tongue and the soft palate in 14
      patients before surgery, and 8 d, 1 month and (in some cases) 6 months after
      surgery. A significant increase in thresholds was observed on the ipsilateral
      side of the tongue after surgery. The extent of the deficit and the recovery time
      course depended on tongue locus. The tip of the tongue displayed a limited
      deficit, suggesting bilateral chorda tympani innervation. The edge of the tongue
      was less impaired than the dorsal or the lateral tip loci; it may be dually
      innervated by both chorda tympani and glossopharyngeal nerves in humans, as
      already shown in rats. Likewise for the fungiform papillae located just anterior
      to the circumvallate papillae. Somatosensory early complaints suggest a
      derepression of chorda tympani on lingual nerve signals. In a second stage,
      relief of complaints before electrogustometric threshold recovery suggested
      trigeminal compensation of the chorda tympani deficit. Relief of complaints seems
      to involve central integrative processes, whereas the evolution of
      electrogustometric threshold represents the actual recovery time course of chorda
      tympani peripheral sensitivity.

PMID- 18821981
TI  - Non-participation and adjustment for bias in case-control studies of
      periodontitis.
AB  - Periodontal researchers frequently use case-control studies, but information on
      participation rates and the reasons for participation are often missing in the
      publications, thus hindering the assessment of the validity of those studies. A
      nested case-control study based on a well-defined population was used to (i)
      describe the patterns of participation; (ii) show how some associations can be
      biased; and (iii) illustrate how inverse probability weights can be applied to
      reduce bias. Differential subject participation was quantified using the ratio
      between participation for each level and the overall participation. Possible
      biased associations were illustrated using the odds ratios found for eligible and
      participant subjects. Finally, we used the estimated probability that an
      individual participates in the case-control study conditional on that
      individual's covariate pattern, as observed in the screening study to attempt
      bias reduction. Considerable differential participation was observed for selected
      factors, including age, annual tuitions and fees, parental income, and parental
      education. The strategy used for adjustment of bias resulted in some degree of
      bias reduction. These findings challenge the inferential validity of many studies
      on periodontitis. The design and conduct of these studies should aim to improve
      subject participation and must consider and minimize this potential source of
      bias.

PMID- 18821982
TI  - Mutations in the EDA gene are responsible for X-linked hypohidrotic ectodermal
      dysplasia and hypodontia in Chinese kindreds.
AB  - X-linked hypohidrotic ectodermal dysplasia (XLHED, OMIM 305100) is a rare
      congenital disorder that results in the defective development of teeth, hair,
      nails, and eccrine sweat glands. Previous studies found that mutations in the
      ectodysplasin A (EDA) gene are associated with XLHED. In the present study, we
      investigated four Chinese families suffering from classical XLHED and
      investigated two additional families segregating hypodontia in an X-linked
      recessive manner. Mutations were characterized respectively in the EDA gene in
      all families, and five of these mutations were found to be novel. Among these
      mutations, five were missense (c.200A>T, c.463C>T, c.758T>C, c.926T>G, and
      c.491A>C) and located in the functional domain of EDA, and one was a splice donor
      site mutation in intron 5 (c.IVS5 + 1G>A), which may result in an alternative
      transcript derived from a new cryptic splice site. Our data further confirm that
      EDA mutations could cause both XLHED and isolated hypodontia and provide evidence
      that EDA is a strong candidate gene for tooth genesis.

PMID- 18821983
TI  - Myelin basic protein is temporospatially expressed in developing rat molars.
AB  - Tooth development occurs through a complex and intricate set of gene-expression
      cascades. Although its early events have been examined extensively, there are
      fewer reports on the late events, such as dental hard-tissue formation. This
      study searched for genes involved in the late stages of tooth development.
      Differential display-polymerase chain reaction revealed myelin basic protein
      (MBP) mRNA to be expressed differentially in the second molar root stage germs
      compared with the third molar cap/early bell stage germs. The MBP expressed
      during hard tissue formation was confirmed to be a 21.5 kDa molecule by Western
      blotting. Immunoreactivity of MBP in the third molar (cap/early bell stage) germs
      was barely detectable in the dental papilla and inner enamel epithelia, whereas
      strong reactivity was noted in the differentiating and differentiated ameloblasts
      and odontoblasts in a temporospatial pattern. However, after complete formation
      of the full-thickness enamel, no reactivity was observed in the maturation-stage
      and protection stage ameloblasts. Myelin basic protein immunoreactive nerve
      fibers were also observed near the developing molar germs. This is the first
      report showing the presence of MBP in dental hard tissue cells, and its
      functional implications should be studied further.

PMID- 18821984
TI  - Thymosin beta4 is cytoprotective in human gingival fibroblasts.
AB  - Thymosin beta4 (Tbeta(4)) is a naturally occurring, ubiquitous, non-toxic protein
      with documented wound-healing, anti-inflammatory, anti-apoptotic, and tissue
      repair properties in skin, the ocular surface, and the heart. The ability of
      Tbeta(4) to demonstrate similar protective properties in cells of the oral cavity
      was analyzed using an in vitro model of cultured human gingival fibroblasts.
      Thymosin beta 4 significantly suppressed the secretion of interleukin-8 (IL-8)
      following stimulation with tumor necrosis factoralpha (TNF-alpha), suggesting
      that it may suppress the inflammatory response initiated by pro-inflammatory
      cytokines. By contrast, Tbeta(4) was not effective in protecting fibroblasts from
      challenge with lipopolysaccharide purified from Porphyromonas gingivalis or
      Escherichia coli. Thymosin beta 4 was able to protect gingival fibroblasts
      against the known cytotoxic effects of chlorhexidine digluconate, a mouthrinse
      containing chlorhexidine digluconate, and carbamide peroxide. Additionally,
      Tbeta(4) was able to protect gingival fibroblasts from the apoptosis that is
      induced by stimulation with TNF-alpha or by exposure to chlorhexidine. Because of
      its multifunctional roles in protecting cells against damage, Tbeta(4) may have
      significant potential for use as an oral heathcare aid with combined
      antimicrobial, anti-inflammatory, anti-apoptotic, and cytoprotective properties.

PMID- 18821985
TI  - The impact of a 17-day training period for an international championship on
      mucosal immune parameters in top-level basketball players and staff members.
AB  - This investigation examined the impact of a 17-d training period (that included
      basketball-specific training, sprints, intermittent running exercises, and weight
      training, prior to an international championship competition) on salivary
      immunoglobulin A (SIgA) levels in 10 subjects (athletes and staff members) from a
      national basketball team, as a biomarker for mucosal immune defence. Unstimulated
      saliva samples were collected at rest at the beginning of the preparation for the
      Pan American Games and 1 d before the first game. The recovery interval from the
      last bout of exercise was 4 h. The SIgA level was measured using enzyme-linked
      immunosorbent assay and expressed as absolute concentrations, secretion rate, and
      SIgA level relative to total protein. The decrease in SIgA levels following
      training was greater in athletes than in support staff; however, no significant
      differences between the two groups were detected. A decrease in SIgA level,
      regardless of the method used to express IgA results, was verified for athletes.
      Only one episode of upper respiratory tract illness symptoms was reported, and it
      was not associated with changes in SIgA levels. In summary, a situation of
      combined stress for an important championship was found to decrease the level of
      SIgA-mediated immune protection at the mucosal surface in team members, with
      greater changes observed in the athletes.

PMID- 18821986
TI  - Waking-state oral parafunctional behaviors: specificity and validity as assessed
      by electromyography.
AB  - In contrast to sleep-related oral parafunctional behaviors, little is known about
      waking oral parafunctional behaviors. The Oral Behaviors Checklist contains terms
      referring to a variety of non-observable behaviors that are reliable when
      prompted (e.g. 'clench') but validity data are absent. Our goal was to assess
      whether (i) each behavioral term is distinct electromyographically, and (ii)
      temporomandibular disorder (TMD) subjects differ from non-TMD subjects in their
      performance. Surface electromyographic (EMG) activity was used to measure
      bilateral masseter, temporalis, and suprahyoid muscles while subjects (27
      patients with TMD; 27 healthy controls) performed ten oral behaviors without
      explanation. Electromyographic data were averaged between bilateral muscles and
      two trials. A multivariate construct (jaw muscle activity) was analyzed using
      Wilks lambda within multivariate analysis of variance (manova). Obvious behaviors
      (e.g. clench, read, tongue press) exhibited expected EMG patterns, and patients
      and controls produced identical profile plots of the EMG data. Of 10 tested
      behaviors, nine were found to be associated with significantly differing
      proportions of amplitudes across muscles and were thus unique. Behaviors with
      similar terms were associated with different EMG patterns. The present data
      support the specificity of behavioral terms and performances. Implications
      include causation related to TMD based on subtle behaviors that occur at a high
      frequency.

PMID- 18821987
TI  - Linking oral health, general health, and quality of life.
AB  - The aim of this work was to assess the association among oral health, general
      health, and quality of life (QoL). The Oral Health Impact Profile (OHIP-49) and
      the RAND-36 were distributed amongst 118 psychology freshmen. Additionally, two
      single items self-rated general health (SRGH) and self-rated oral health (SROH) -
      were administered. Kruskal-Wallis and Mann-Whitney U-tests were used to evaluate
      differences between SRGH and SROH categories, regarding OHIP subscale scores and
      RAND subscale scores. More than 75% of the subjects rated their oral and general
      health as good. Mean OHIP scores and RAND scores indicated a relatively good oral
      and general health-related QoL respectively. The correlation between oral and
      general health was weak. Significant differences were found between SRGH
      categories regarding RAND subscale scores, except for the 'role emotional' and
      'mental health' subscales. Significant differences were also found between SROH
      categories regarding OHIP subscale scores, except for the 'psychological
      disability' subscale. However, no significant differences were found between SRGH
      categories regarding OHIP subscale scores, or between SROH categories regarding
      RAND subscale scores. The findings suggest that oral health, general health, and
      QoL have different determinants. Furthermore, oral health and general health
      appear to be mostly unrelated in this seemingly healthy population. It is
      proposed that if no apparent disease is present, oral and general health must be
      regarded as separate constructs.

PMID- 18821988
TI  - Dental pain and care-seeking in 11-14-yr-old adolescents in a low-income country.
AB  - The purpose of this article was to document the 1-month dental pain prevalence in
      11-14-yr-old subjects attending Grade Six of middle schools in Peshawar,
      Pakistan, and to explore the effect of dental pain and the impact on daily living
      on dental care-seeking. A self-completed questionnaire survey of all 13 middle
      schools in University Town, Peshawar, Pakistan, was carried out in April 2007.
      Questionnaire items on dental pain were adapted from the dental pain screening
      questionnaire (DePaQ) and items on the impact on daily living were adapted from
      the child-oral impact on daily performance (OIDP-Child) questionnaire. Regression
      analysis was carried out to determine the relative usefulness of predictors for
      care-seeking. The prevalence of dental pain was estimated to be 30.4%, and care
      seeking in those reporting pain was estimated to be 64%. Care-seeking was
      associated with 'pain felt in one tooth', 'painful tooth felt loose',
      'difficulties sleeping', and 'difficulties playing', which accounted for 35% of
      the explained variance. The findings substantiate dental pain as an important
      dental public health concern in Pakistan and support the hypothesis that
      assessment of dental pain characteristics can add to the accuracy of dental need
      estimation.

PMID- 18821989
TI  - Toothache prevalence and associated factors: a life course study from birth to
      age 12 yr.
AB  - This study estimated the lifetime prevalence of toothache at ages 6 and 12 yr,
      the prevalence of toothache during the last month, and their association with
      social, behavioural and clinical exposures in the course of life of 339 12-yr-old
      children from a birth cohort in Pelotas, Brazil. Exploratory variables were
      collected in the perinatal study and during several follow-up studies. Prevalence
      ratios were calculated using Poisson regression, following a hierarchical
      conceptual model. The lifetime prevalence of toothache at ages 6 and 12 yr were
      39% [95% confidence interval (CI) = (34;45)] and 63% [95% CI = (58;69)],
      respectively. Toothache during the last month was reported by 11% [95% CI =
      (8;15)]. Children who did not live with their biological father at birth, and
      children with higher dmf-t counts, reported a higher lifetime prevalence of
      toothache at age 6 yr. Children experiencing poverty between ages 0 and 4 yr,
      with higher dmf-t and DMF-T indexes presented a greater lifetime prevalence of
      toothache at 12 yr. Toothache within the last month was more likely to be
      reported by girls and by children who did not live with their biological father
      at birth. Preventive strategies should be implemented in early stages of the life
      cycle, taking into account the socio-economic and family context in which pain
      mostly occurs.

PMID- 18821990
TI  - Diagnostic accuracy of digitized periapical radiographs validated against micro
      computed tomography scanning in evaluating orthodontically induced apical root
      resorption.
AB  - The aim of this study was to validate the use of digitized periapical radiographs
      in evaluating orthodontically induced apical root resorption against micro
      computed tomography (micro-CT) scanning as a criterion standard test. In a
      standardized experimental protocol, 29 premolars in 16 subjects were tipped
      buccally for 8 wk. Nineteen contralateral premolars not subjected to orthodontic
      movement served as controls. Standardized periapical radiographs were taken
      before and after the experimental period (Rx method). These teeth were extracted
      and scanned using a micro-CT technique with a 9 mum resolution. Two calibrated
      examiners assessed blindly the presence or absence of apical root resorption on
      digitized radiographs and three-dimensional reconstructions of the scans.
      Significant differences were detected between the orthodontically moved teeth and
      controls: 86% of the orthodontically moved teeth and 21% of the control teeth
      showed apical root resorption when using micro-CT as a validation method. A total
      of 55% of the experimental teeth and 5% of the control teeth showed resorption
      when assessed using Rx method. The Rx method showed a specificity of 78% and a
      sensitivity of 44%, which means that less than half of the cases with root
      resorption identified using a CT scanner were identified by radiography. Nearly
      all the orthodontically moved teeth showed apical root resorption. Apical root
      resorption may be underestimated when evaluated using digitized periapical
      radiographs.

PMID- 18821991
TI  - Inhibition of hydroxyapatite dissolution by whole casein: the effects of pH,
      protein concentration, calcium, and ionic strength.
AB  - Formulating drinks with reduced erosive potential is one approach for reducing
      dental erosion. In this study, whole casein was added to citric acid solutions
      representative of soft drinks, and the hydroxyapatite dissolution rate was
      assessed. Adding 0.02% (w/v) casein to acid solutions significantly reduced the
      hydroxyapatite dissolution rate by 51 +/- 4% at pH values of 2.80, 3.00, 3.20,
      3.40, and 3.60, although the baseline dissolution rates of course varied as a
      function of pH. The protein concentration [0.002, 0.02, and 0.2% (w/v) casein]
      had no significant effect on dissolution inhibition. Adding both casein and
      calcium to citric acid resulted in a further reduction in the dissolution rate at
      low and intermediate calcium concentrations (5 and 10 mM) but not at higher
      calcium concentrations (20 and 50 mM). Ionic strength had no significant impact
      on the efficacy of casein. Casein also significantly reduced the hydroxyapatite
      dissolution rate when the hydroxyapatite was coated with a salivary pellicle. The
      reduction in dissolution rate is ascribed to firmly adsorbed casein on the
      hydroxyapatite surface, which stabilizes the crystal surface and inhibits ion
      detachment.

PMID- 18821992
TI  - Bioactive glass-ionomer cement with potential therapeutic function to dentin
      capping mineralization.
AB  - We have developed a novel bioactive resin-modified glass-ionomer cement system
      with therapeutic function to dentin capping mineralization. In the system, the
      newly synthesized star-shape poly(acrylic acid) was formulated with water, Fuji
      II LC filler, and bioactive glass S53P4 to form resin-modified glass-ionomer
      cement. Compressive strength (CS) was used as a screening tool for evaluation.
      The commercial glass-ionomer cement Fuji II LC was used as a control. All the
      specimens were conditioned in simulated body fluid (SBF) at 37 degrees C prior to
      testing. The effect of aging in SBF on CS and microhardness of the cements was
      investigated. Scanning electron microscopy was used to examine the in vitro
      dentin surface changes caused by the incorporation of bioactive glass. The
      results show that the system not only provided strengths comparable to original
      commercial Fuji II LC cement but also allowed the cement to help mineralize the
      dentin in the presence of SBF. It appears that this bioactive glass-ionomer
      cement system has direct therapeutic impact on dental restorations that require
      root surface fillings.

PMID- 18821993
TI  - An in vitro investigation of the effectiveness of bioactive glass air-abrasion in
      the 'selective' removal of orthodontic resin adhesive.
AB  - The process of clinically debonding orthodontic brackets causes
      histomorphological damage to enamel that needs to be quantified and minimized.
      This study compared three methods for removing residual resin adhesive following
      bracket debonding. The surface finish following removal of residual adhesive
      using a slow-speed eight-bladed tungsten carbide bur (group 1), alumina air
      abrasion (group 2), and bioactive-glass air-abrasion (group 3) and following
      polishing, was examined using scanning electron microscopy imaging of resin
      replicas. Contact profilometry was used to image surfaces before and after
      debonding for quantifiable volumetric analysis of enamel damage. Surface scarring
      was seen on scanning electron micrographs from group 1, a sharp pitted surface
      was identified in group 2, while group 3 exhibited similar, but subjectively
      smoother, pits. The surface finish following polishing was similar for groups 2
      and 3 but did not completely remove the scarring evident from group 1.
      Quantifiable enamel lost was as follows: group 1, 0.285 mm(3); group 2, 0.386
      mm(3); and group 3, 0.135 mm(3); statistical differences were observed between
      groups 2 and 3. From these results, bioactive-glass air-abrasion more
      consistently caused less physical damage to enamel and achieved a clinically
      smooth surface finish following polishing and is therefore to be recommended for
      clinical use.

PMID- 18821994
TI  - Influence of a chitosan on oral bacterial adhesion and growth in vitro.
AB  - Generally, mechanical plaque control without chemical support is insufficient to
      prevent oral diseases, and an ongoing quest exists for new antimicrobials for use
      in oral healthcare. Chitosans are polycationic, naturally occurring
      antimicrobials that are rapidly finding their way into oral healthcare. In this
      study we determined the effects of pellicle treatment with chitosan on bacterial
      adhesion and growth. Chitosan caused a reduction in bacterial adhesion and was
      responsible for bacterial death upon contact compared with a buffer control.
      Exposure of adhering bacteria to a chitosan solution or a buffer control did not
      cause detachment, but the chitosan solution left a small proportion of the
      adhering bacteria alive. Growth after exposure to chitosan was similar to
      (Streptococcus mutans ATCC700610, Streptococcus oralis HM1, Streptococcus
      sobrinus HG1025) or less than (S. mutans NS, Actinomyces naeslundii HM1) that of
      the control, while biofilm viability after chitosan treatment was lower than that
      of the control, except for S. oralis HM1. Therefore, chitosan is a promising
      antimicrobial for use in oral healthcare.

PMID- 18821996
TI  - Reducing psychotropic medications in elderly rehabilitation inpatients with a
      fall-related admission: how often is it happening?
AB  - AIM: To assess the frequency of psychotropic medication withdrawal in an
      inpatient geriatric rehabilitation population with a fall-related admission
      diagnosis. METHODS: A retrospective medical record audit. The medical records
      department randomly selected 100 patients admitted between October 2006 and April
      2007 to the geriatric rehabilitation ward of Casey Hospital with a fall-related
      admission diagnosis. RESULTS: The population was predominantly female (71%) and
      elderly (average age, 80 years) with the vast majority of patients living at home
      (88%) prior to admission. Twenty-six of 49 (53%) of patients admitted on
      psychotropic medication were on a reduced regime by discharge (reduced dose or
      number of psychotropic medications). Just 7 of 100 patients had an increased
      psychotropic medication regime by discharge. Benzodiazepines were far more likely
      to be reduced (20/24, 83%) than other psychotropic medications. CONCLUSION: This
      audit does suggest an acceptable awareness in this geriatric rehabilitation
      setting of the fall risk posed by psychotropic medication. It needs to be further
      explored why benzodiazepines are so much more likely to be reduced in this
      population than other psychotropic medications, despite those other types also
      posing a significant fall risk.

PMID- 18821997
TI  - Validity and reliability of the Physical Activity Scale for the Elderly (PASE) in
      Japanese elderly people.
AB  - AIM: In Japan, there are no valid and reliable physical activity questionnaires
      for elderly people. In this study, we translated the Physical Activity Scale for
      the Elderly (PASE) into Japanese and assessed its validity and reliability.
      METHODS: Three hundred and twenty-five healthy and elderly subjects over 65 years
      were enrolled. Concurrent validity was evaluated by Spearman's rank correlation
      coefficient between PASE scores and an accelerometer (waking steps and energy
      expenditure), a physical activity questionnaire for adults in general (the Japan
      Arteriosclerosis Longitudinal Study Physical Activity Questionnaire, JALSPAQ),
      grip strength, mid-thigh muscle area per bodyweight, static valance and bodyfat
      percentage. Reliability was evaluated by the test-retest method over a period of
      3-4 weeks. RESULTS: The mean PASE score in this study was 114.9. The PASE score
      was significantly correlated with walking steps (rho = 0.17, P = 0.014), energy
      expenditure (rho = 0.16, P = 0.024), activity measured with the JALSPAQ (rho =
      0.48, P < 0.001), mid-thigh muscle area per bodyweight (rho = 0.15, P = 0.006)
      and static balance (rho = 0.19, P = 0.001). The proportion of consistency in the
      response between the first and second surveys was adequately high. The intraclass
      correlation coefficient for the PASE score was 0.65. CONCLUSIONS: The Japanese
      version of PASE was shown to have acceptable validity and reliability. The PASE
      is useful to measure the physical activity of elderly people in Japan.

PMID- 18821998
TI  - Mortality rates of community-residing adults with and without dentures.
AB  - AIM: To prospectively study how dental status with and without dentures could
      become a predictor of overall mortality risk. METHODS: Five thousand six hundred
      eighty-eight community residents over 40 years old in the Miyako Islands, Okinawa
      Prefecture, Japan, were followed up for 15 years from 1987-2002. RESULTS: We
      found that female subjects with less than 10 functional teeth and without
      dentures showed a significantly higher mortality rate than those with dentures.
      There was no significant difference of mortality rates in male subjects. There
      were no significant differences of mortality rates between subjects with 10 or
      more functional teeth with and without dentures. CONCLUSION: The present study
      suggests that dentures are one of the factors associated with mortality rates
      especially in female subjects with less than 10 functional teeth.

PMID- 18821999
TI  - Daily blood glucose profiles of glibenclamide and gliclazide taken once or twice
      daily in elderly type 2 diabetic patients.
AB  - AIM: The aim of this study was to evaluate the difference in daily blood glucose
      profiles between once- and twice-daily regimens of a moderate daily dose of
      glibenclamide or gliclazide in elderly patients with type 2 diabetes. METHODS:
      Daily blood glucose profile data were evaluated in 18 elderly type 2 diabetic
      patients treated with 80 mg/day gliclazide or 5 mg/day glibenclamide as
      monotherapy. The first daily blood glucose profile of the twice-daily regimen was
      performed approximately 1 week before hospital discharge, and the second was
      performed after taking a once-daily regimen for 4-7 days. Plasma glucose and
      plasma immunoreactive insulin (IRI) concentrations were measured daily at 12 time
      points: 08.00 (before breakfast); 10.00; 12.00 (before lunch); 14.00; 18.00
      (before dinner); 20.00; 0.00; 02.00; 03.00; 04.00; 06.00; and 08.00 hours the
      next morning. RESULTS: Daily blood glucose profiles and plasma IRI profiles did
      not differ between the once- and twice-daily regimen groups in either the
      gliclazide group or the glibenclamide group. Plasma glucose values between
      midnight and early morning tended to be lower than the 08.00 hours plasma glucose
      value in the glibenclamide group, but not in the gliclazide group. CONCLUSION:
      These results suggest that the blood glucose-lowering effects of a once- and
      twice-daily moderate daily dose of glibenclamide or gliclazide do not differ in
      elderly type 2 diabetic patients. However, glibenclamide, regardless of the
      dosage schedule, tends to lower the plasma glucose values between midnight and
      early morning.

PMID- 18822000
TI  - In-depth descriptive analysis of trends in prevalence of long-term care in Japan.
AB  - BACKGROUND: Long-term care (LTC) insurance was introduced in Japan in 2000.
      Herein, we describe the trends in demand for LTC, using age-standardized and
      level-specific rates of entitlement and utilization of LTC at national and
      prefectural levels. METHODS: We analyzed LTC data from 2002-2005 to examine: (i)
      the influence of population aging, calculating crude and age-standardized
      entitlement and utilization rates; (ii) the relation between baseline entitlement
      rate and increase in the rate over this 3-year period; and (iii) differences in
      increases in entitlement rate between low and high care levels. RESULTS: The
      entitlement and utilization rates increased even after adjustment for age;
      approximately two-thirds of the increase was not due to population aging.
      Variations in the entitlement rates among prefectures did not decrease
      (coefficient of variance was 0.12 in 2002 and 0.11 in 2005), and there was no
      significant correlation between baseline entitlement rates and the later
      increases among prefectures (r = -0.20, P = 0.19). The increase in entitlement
      rate was larger for low than for high care levels (31% vs 6%), and those for low
      and high care levels were weakly correlated. CONCLUSION: This study suggested
      that a large part of the increase in LTC demand could not be explained by
      population aging, and the increase did not result from equalization of LTC
      services across the country. In addition, it seems that the demands of low and
      high care levels depend on different factors. The increase in LTC demand should
      be monitored carefully to identify underlying factors and to ensure
      sustainability of the system.

PMID- 18822001
TI  - Effects of aging and sex on progression of carotid intima-media thickness: a
      retrospective 6-year follow-up study.
AB  - AIM: We retrospectively examined the relationship of aging, sex and risk factors
      to increased carotid intima-media thickness (IMT) over a follow-up period of 6
      years in patients with multiple risk factors. METHODS: Subjects were comprised of
      463 patients (287 men, 176 women) with a mean age of 64 +/- 0.4 years who had
      undergone carotid ultrasonography twice or more at intervals of 5 years or older.
      The mean follow-up period was 6.0 +/- 0.1 years. RESULTS: Mean baseline IMT for
      all subjects was 1.40 +/- 0.02 mm, and no significant difference was seen between
      sexes. Mean IMT after 6 years for all subjects was 1.84 +/- 0.03 mm, and was
      significantly greater in men than in women. Mean annual increase in IMT (Delta
      IMT) for all subjects was 0.073 +/- 0.005 mm/year, with a significant positive
      correlation between baseline age and Delta IMT (r = 0.11, P < 0.05), and Delta
      IMT was significantly greater in men than in women (0.087 +/- 0.007 mm vs 0.050
      +/- 0.007 mm, P < 0.001). IMT increased with age in both men and women, but Delta
      IMT increased with age only in men. Multivariate analysis showed baseline age and
      diabetes mellitus as significant risk factors with baseline IMT as the objective
      variable. Age and sex represented significant risk factors with DeltaIMT as the
      objective variable. CONCLUSION: Sex differences exist in the relationship between
      increases in IMT and age. Age, sex and diabetes mellitus represented the main
      risk factors.

PMID- 18822002
TI  - Age and sex differences in various stepping movements of the elderly.
AB  - AIM: This study aimed to examine sex and age differences of various stepping
      movements in the elderly and to clarify useful stepping movements for evaluation
      of their dynamic balance. METHODS: Two hundred and eighty-six healthy elderly
      subjects who could walk independently (male mean age = 71.2 +/- 7.1 years; female
      mean age = 71.5 +/- 6.0) performed the following stepping tests: back and forth;
      up and down with a 5 cm tall step; and in-place stepping matching three tempos
      (44, 66 and 132 b.p.m.). Step number, single and double support times in the
      former two stepping tests, and time difference between metronome sound and
      grounding time in the latter tempo stepping tests were selected as evaluation
      parameters. RESULTS: An insignificant sex difference was found in all parameters.
      Hence, the data of men and women was pooled to examine age differences.
      Significant age differences were found in the step number and double support time
      of back and forth and up and down stepping tests and in the time difference of
      three tempo stepping tests. The step number in younger age groups and the support
      times in older age groups tended to be larger. CONCLUSION: No sex difference was
      found in evaluation parameters of all stepping tests, and all parameters tended
      to be superior in the younger elderly. The elderly experienced more difficulty
      matching slow tempos than fast tempos in the in-place stepping test. The back and
      forth, up and down and in-place matching tempo stepping tests may be useful for
      evaluating dynamic balance ability of the elderly.

PMID- 18822003
TI  - Body-sway characteristics during a static upright posture in the elderly.
AB  - AIM: This study aimed to determine the reliability and sex and age-level
      differences of body-sway parameters, based on center of pressure (COP)
      measurements, during a static upright posture in the elderly and to clarify their
      body-sway characteristics in comparison with those of young adults. METHODS: The
      subjects were 50 healthy elderly and 50 healthy young adults. They had no
      evidence or known history of disorder. The data sampling frequency was 20 Hz.
      Thirty-six highly reliable parameters were selected from the following seven
      domains: distance; position; distribution of amplitude; area; velocity; power
      spectrum; and vector. In addition, four body-sway factors (unit time sway, front
      back sway and a left-right sway and the high-frequency band power) were also
      measured. RESULTS: In the elderly, most body-sway parameters had very high
      reliability and did not show significant sex or age-level differences. The degree
      of body sway was greater in the elderly than in young adults, and marked
      differences were found, especially in sway velocity and periodicity. The four
      body-sway factors showed almost the same tendency as the 32 sway parameters.
      CONCLUSION: We judged that the body sway in the elderly showed large individual
      differences. Approximately 10% of the elderly subjects may be outside the
      standard range as compared to young adults, mainly in parameters relating to
      velocity and spectrum. Because the body-sway characteristics of the elderly are
      considerably different from those of young adults, we may need unique criteria to
      evaluate their body sway.

PMID- 18822004
TI  - Undiagnosed cirrhosis occurs frequently in the elderly and requires periodic
      follow ups and medical treatments.
AB  - BACKGROUND: Autopsy examinations frequently reveal undiagnosed cirrhosis, but its
      characteristics have rarely been addressed in the elderly. METHODS: From 1597
      consecutive autopsies, those of patients with liver cirrhosis were selected and
      their clinicopathological findings were examined. RESULTS: Seventy-six patients
      had liver cirrhosis; 18 of these patients (23.7%) were classified as an
      "undiagnosed" group and in that they had not been diagnosed as having cirrhosis
      before death. The remaining 58 patients were classified as a "clinical" group.
      Compared to the clinical group, the undiagnosed group demonstrated a
      significantly lower Child-Pugh score (7.1 +/- 1.9 vs 8.6 +/- 2.1; P < 0.01) and
      infrequent hepatocellular carcinoma (72.4% vs 5.6%; P < 0.0001). The undiagnosed
      group also demonstrated significantly lower complication rates of hepatic
      encephalopathy and esophageal varix, and a volume of ascites. The patients in the
      undiagnosed group were significantly older (79.9 +/- 8.1 vs 74.2 +/- 8.5 years; P
      < 0.01), and fewer patients died of liver-related causes (17% vs 67.2%; P <
      0.0001). The etiology of cirrhosis was unknown in five patients in the
      undiagnosed group, and seven patients did not show any suggestive symptoms or
      imaging signs. CONCLUSION: Liver cirrhosis is often undiagnosed (23.7%) in the
      elderly. In the undiagnosed group, liver function was preserved and serious
      complications were infrequent. Because the diagnosis of cirrhosis leads to early
      identification of hepatocellular carcinoma and good prognosis, detailed
      examination and periodic follow ups should be performed when liver dysfunction is
      indicated, even in the elderly.

PMID- 18822005
TI  - Effects of olopatadine in limited scleroderma with peripheral eosinophils.
AB  - Scleroderma and eosinophilia often occur together, though the pathogenesis is
      unclear. We investigated the effect of olopatadine hydrochloride in a series of
      cases of limited scleroderma (LS). Ten patients with LS and positive eosinophil
      counts (LSE) were enrolled (average age, 85 years; six men and four women). Serum
      concentrations of the anti-Scl-70 antibody were positive. Olopatadine
      hydrochloride was prescribed at 10 mg/day for 3 weeks. Serum concentrations of
      the anti-Scl-70 antibody significantly decreased, but changes in eosinophil
      numbers and percentages in peripheral blood were not significant. Factor analysis
      suggested a correlation between serum concentrations of the anti-Scl-70 antibody
      and complement C4. Olopatadine could be effective in reducing anti-Scl-70
      antibodies in the elderly with LSE.

PMID- 18822006
TI  - White matter lesions and endothelial dysfunction measured by pulse wave analysis.

PMID- 18822007
TI  - Terminal illness - the right to choose.

PMID- 18822009
TI  - Abstracts of the XXVII International Congress of the International Academy of
      Pathology. October 12-17, 2008. Athens, Greece.

PMID- 18822010
TI  - Root canal morphology of mandibular permanent molars at different ages.
AB  - AIM: To investigate differences in the root canal morphology of permanent
      mandibular molar teeth at various ages. METHODOLOGY: Four hundred and eighty
      permanent mandibular first and second molars were examined. First and second
      molars were divided into six and five groups, respectively, according to the age
      of the patient at the time of extraction. Root canal morphology was studied using
      a clearing technique. The canal morphology of the mesial root was classified into
      three stages depending on its developmental pattern. When the root canal system
      was completely differentiated, the canal classification and the number of lateral
      canals and inter-canal communications were recorded. Vertucci's classification
      was taken as the main reference. Canal morphology was compared amongst age
      groups. RESULTS: In both first and second molars, developmental stages of canal
      morphology amongst age groups were significantly different (P < 0.0001). The
      prevalence of inter-canal communications was highly significantly different in
      the first (P < 0.0001) and less significant in the second molar (P < 0.05). After
      completion of the canal differentiation, the mesial roots of first molars had
      type IV and II canal forms. The majority of the mesial roots of second molars had
      type I and III canals. C-shaped canals were found in 3% of second molars.
      CONCLUSIONS: Mesial roots of first and second molars mostly had one large canal
      until 11 and 15 years of age, respectively. In both molars, the canal system was
      completely defined at 30-40 years. The prevalence of inter-canal communications
      was low at young and old ages but high at intermediate ages.

PMID- 18822011
TI  - Effectiveness of different gutta-percha techniques when filling experimental
      internal resorptive cavities.
AB  - AIM: To determine the quality of root fillings in teeth with artificial internal
      resorptive cavities filled with Thermafil, JS Quick-Fill, Soft Core, System B and
      Microseal, and by cold lateral compaction (LC) technique. METHODOLOGY: Sixty
      maxillary incisor teeth were selected. After access cavity preparation and root
      canal instrumentation, the roots were sectioned horizontally and artificial
      internal resorption cavities were prepared on the canal walls. The tooth sections
      were cemented together and the root canals were filled using one of six different
      techniques: Thermafil, JS Quick-Fill, Soft Core, System B and Microseal, and by
      LC. The roots were then divided at the level of the previous section and each
      root surface was photographed. Image analysis program was used to calculate the
      percentage of sealer, gutta-percha and void in the internal resorptive cavities.
      All measurements were analysed statistically using One-way ANOVA and Newman-Keuls
      tests. RESULTS: The Microseal technique filled 99% of the artificial resorptive
      area followed by LC (92%), SystemB (89%), Quick-Fill (88%), Thermafil (74%) and
      Soft-Core (73%). Warm gutta-percha compaction techniques filled the resorption
      areas with more gutta-percha than sealer (Microseal 68%, System B 62%) compared
      to the other techniques (LC 48%, Quick Fill 41%, Soft Core 34%, Thermafil 35%).
      In addition, core techniques left a considerable volume of voids in the
      resorptive areas (Quick-Fill 12%, Thermafil 26%, Soft Core 27%). CONCLUSIONS:
      Warm gutta techniques filled artificial resorption cavities significantly better
      than the other gutta-percha techniques.

PMID- 18822012
TI  - Substance P influenced gelatinolytic activity via reactive oxygen species in
      human pulp cells.
AB  - AIM: To investigate the effects of substance P (SP) on gelatinolytic activity of
      matrix metalloproteinases (MMPs) in human pulp cells. METHODOLOGY: Human dental
      pulp cells were isolated and cultured. Subconfluent cells, between the third and
      sixth passages, were maintained under serum deprivation for 18 h followed by the
      treatment of varying doses of SP (1 pmol L(-1), 100 pmol L(-1), 10 nmol L(-1), 1
      micromol L(-1) and 100 micromol L(-1)). Conditioned media were then subjected to
      gelatin zymography using 8% sodium dodecyl sulphate polyacrylamide gel
      electrophoresis minigels containing 1.5 g L(-1) gelatin. The effect of SP on
      intracellular reactive oxygen species (ROS) was also examined by confocal
      microscopy. ROS scavenger N-Acetyl-L-cysteine (NAC, 5 mmol L(-1)) was utilized to
      evaluate the roles of ROS pathway in mediating the impact of SP on cellular
      gelatinolytic activity. Data were analysed using analysis of variance with
      Bonferroni correction for multiple comparisons or an unpaired Student's t-test.
      RESULTS: Substance P, at levels above 1 micromol L(-1), remarkably enhanced MMP-2
      activity reflected by the band migrating at 66 kDa (P < 0.05). A gelatinolytic
      band at approximately 44 kDa appeared to be intensified in a SP dose-dependent
      manner. In addition, it was demonstrated that SP could induce ROS production in
      pulp cells and ROS scavenger NAC was further found to significantly reduce MMP-2
      activity (P < 0.05), as well as other bands of gelatinolytic proteinases.
      CONCLUSION: Substance P can influence gelatinolytic activity in human pulp cells
      via ROS pathway.

PMID- 18822013
TI  - Dentinal tubule invasion and adherence by Enterococcus faecalis.
AB  - AIM: To investigate dentinal tubule invasion and the predilection of Enterococcus
      faecalis for dentinal tubule walls. METHODOLOGY: The invasion of dentinal tubules
      in extracted human teeth by E. faecalis was measured ex vivo after 8 weeks of
      incubation. The canal walls of 16 root sections were either intact or
      instrumented with or without smear layer present. Extent and maximum depth of
      tubule invasion were assessed histologically and compared between groups. In the
      adherence study, 44 vertically split root samples were prepared to expose
      longitudinally aligned dentinal tubules and fractured orthodentine (OD). Surfaces
      were exposed to E. faecalis (erythromycin resistant strain, JH2-2 carrying
      plasmid pGh9:ISS1) and incubated aerobically for 2 h. Samples were processed for
      analysis using scanning electron microscopy. Bacterial adhesion to tubule walls
      versus fractured OD was calculated as number of cells per 100 microm(2). RESULTS:
      The strain of E. faecalis used in this study showed moderate to heavy tubule
      invasion after 8 weeks. In the adhesion studies, significantly more bacteria
      adhered to fractured OD than to dentinal tubule walls (ANOVA, P < 0.001). With
      respect to the tubule wall, adherence was greater in inner versus outer dentine
      (P = 0.02) and greater when bacterial adhesion was tested in chemically defined
      medium than in phosphate-buffered saline (ANOVA, P < 0.001). CONCLUSIONS:
      Although E. faecalis readily invaded tubules, it did not adhere preferentially to
      tubule walls. Initial colonization of dentinal tubules by E. faecalis may depend
      primarily on other factors.

PMID- 18822014
TI  - Effect of canal preparation and residual root filling material on root impedance.
AB  - AIM: To investigate the effect of root canal preparation and residual root
      filling material on the impedance characteristics of extracted human roots.
      METHODOLOGY: Thirty extracted, human single-rooted teeth were mounted in a custom
      made apparatus that allowed strict temperature control. Impedance measurements of
      the roots were made with a file acting as the internal electrode, using a
      frequency response analyser. The measurements were made under three canal
      conditions: (i) before chemo-mechanical preparation; (ii) after chemo-mechanical
      preparation; (iii) after root filling removal to re-establish patency (following
      placement of root filling). The measurements were taken at 0, 0.5, 1, 2, 3, 4, 5,
      6, 7, 8, 9 and 10 mm coronal to the apical terminus and also at 0.5 and 1 mm past
      the apical terminus. Impedance values were viewed using Nyquist plots and
      comparisons made within each tooth, between measurement points along the length
      of the canal, as well as under the different canal conditions. Equivalent
      circuits were modelled for different test conditions. RESULTS: The impedance
      decreased from the coronal to the apical levels in all canal conditions in a
      characteristic way, with an exaggerated drop at the apical terminus. Impedance
      decreased after chemo-mechanical preparation, but gave higher values compared
      with before or after instrumentation, once canal filling had been removed.
      Equivalent circuits remained consistent at the tested positions within the canal,
      regardless of canal condition, but the circuit component values changed with the
      impedance. CONCLUSIONS: Impedance was influenced by corono-apical position, chemo
      mechanical preparation and residual root canal filling material.

PMID- 18822016
TI  - Smoking cessation--medicine must triumph over politics.

PMID- 18822017
TI  - The five 'Ps' of an incontinence clinical practice guideline.

PMID- 18822018
TI  - Risks of chest drain insertion.

PMID- 18822019
TI  - How important are metalloproteinases in aortic dissection?

PMID- 18822020
TI  - Muddy waters: more stormy SEAS for ezetimibe.

PMID- 18822021
TI  - Long-term efficacy and safety of ezetimibe 10 mg in patients with homozygous
      sitosterolemia: a 2-year, open-label extension study.
AB  - OBJECTIVE: To assess the long-term efficacy and safety profile of ezetimibe 10
      mg/day in patients with homozygous sitosterolemia. METHODS: This was an extension
      of a multi-centre, randomised, double-blind, placebo-controlled base study in
      which patients with homozygous sitosterolemia and plasma sitosterol
      concentrations > 5 mg/dl were randomised 4 : 1 to ezetimibe 10 mg/day (n = 30) or
      placebo (n = 7) for 8 weeks. Patients who successfully completed the base study
      with > 80% compliance to study medication were eligible to enter two, successive,
      1-year extension studies in which ezetimibe 10 mg/day was administered in an open
      label manner. Patients remained on their current treatment regimen (e.g. bile
      salt-binding resins, statins and low-sterol diet) during the base and extension
      studies. Patients had to be off ezetimibe therapy for > or = 4 weeks prior to
      entering the first extension. Efficacy and safety/tolerability parameters were
      evaluated every 12 and 26 weeks in the first and second years respectively. The
      primary efficacy end-point was mean percentage change in plasma sitosterol from
      baseline to study end for the cohort of patients (n = 21) who successfully
      completed the second extension study. RESULTS: Treatment with ezetimibe 10 mg/day
      led to significant mean percentage reductions from baseline in plasma
      concentrations of sitosterol (-43.9%; p < 0.001), campesterol (-50.8%; p <
      0.001), low-density lipoprotein (LDL) sterols (-13.1%; p < 0.050), total sterols
      (-10.3%; p < 0.050) and apolipoprotein (apo) B (-10.1%; p < 0.050). No
      significant changes from baseline were observed for lathosterol, high-density
      lipoprotein sterol, triglycerides or apo A-1. Maximal reductions in sitosterol
      and campesterol occurred within the first 52 weeks of treatment and were
      sustained for the duration of the study. For LDL sterol, total sterols and apo B,
      maximal reductions were achieved early (by weeks 4 or 16) and waned slightly
      through the remainder of the study. Overall ezetimibe 10 mg was well tolerated.
      CONCLUSION: In patients with homozygous sitoserolemia, long-term treatment with
      ezetimibe 10 mg/day for 2 years was effective in reducing plasma plant sterol
      concentrations with an overall favourable safety and tolerability profile.

PMID- 18822022
TI  - Prevalence and risk factors of metabolic syndrome in Brazilian and Italian obese
      adolescents: a comparison study.
AB  - BACKGROUND: Metabolic syndrome (MS) prevalence between different populations in
      obese adolescents is scanty to date. OBJECTIVE: To compare the MS prevalence and
      related risk factors in Brazilian and Italian obese adolescents. METHODS: A total
      of 509 adolescents (110 Brazilian, 399 Italian), aged 15-19 years. Anthropometric
      characteristics, triglycerides (TG), total, low-density lipoprotein (LDL)-, high
      density lipoprotein (HDL)-cholesterol, fasting plasma glucose (FPG), insulin,
      homeostasis model assessment of insulin resistance (HOMA-IR) and blood pressure
      were measured. RESULTS: Age, body mass index (BMI) and BMI z-score were not
      significantly different between the two subgroups. BMI z-score, TG, FPG, HOMA-IR
      and systolic blood pressure (SBP) were significantly higher in boys than in girls
      both in Brazilian and Italian adolescents, while HDL-cholesterol levels were
      lower in boys than in girls. No significant differences were observed in BMI, LDL
      and total-cholesterol and DBP in two genders and groups. Insulin, FPG, HOMA-IR
      and TG were significantly higher, while LDL-cholesterol and SBP were
      significantly lower in Brazilian than in Italian subjects, both in males and
      females. HDL and total-cholesterol and diastolic blood pressure (DBP) were not
      significantly different between the two subgroups and genders. MS prevalence was
      higher in Brazilian than in Italian obese boys (34.8 vs. 23.6%, p < 0.001) and
      girls (15.6 vs. 12.5%, p < 0.01). The most frequently altered parameter was HOMA
      IR both in subjects with MS (100% in Brazilian and 81.8% in Italian) and without
      MS (42.9% and 11.7%). CONCLUSION: Metabolic syndrome represents a worldwide
      emerging health problem in different ethnical populations, the alterations of the
      risk factors related to MS (different in their prevalence between different
      subgroups) being strictly linked to the degree of obesity.

PMID- 18822023
TI  - Current practice and resource utilisation in men diagnosed with premature
      ejaculation.
AB  - OBJECTIVES: To compare the healthcare resource utilisation of men diagnosed with
      premature ejaculation (PE) with that of age-matched men without a PE diagnosis,
      through a retrospective analysis of US medical claims data. METHODS: Data were
      from the PHARMetrics Database. Records of patients > or = 18 years of age
      diagnosed with PE (n = 1245) and age-matched controls (n = 3915) were compared
      with regard to number of physician encounters, concomitant medical diagnoses,
      drug therapies and treatment costs. RESULTS: Men diagnosed with PE visited their
      physicians twice as frequently in the year before their diagnosis as men in the
      control group. Men diagnosed with PE were more likely to receive a prescription
      for a selective serotonin reuptake inhibitor or a phosphodiesterase-5 inhibitor
      after their diagnosis than before and used more of these compared with controls.
      Prior to their PE diagnosis, patients received more (and more frequent) comorbid
      diagnoses than controls, and their mean yearly diagnosis and prescription costs
      were $1320 (vs. $447 for controls). In the year after the PE diagnosis, diagnosis
      and prescription costs fell by 24% (to $998), primarily because of a reduction in
      physician visits. CONCLUSIONS: Compared with controls, men with PE who sought
      help from a healthcare professional consumed more medical resources, primarily
      because of a higher number of physician visits and greater use of prescription
      drugs. Further research is warranted to determine if the observed associations
      between PE and other diagnoses indicate genuine aetiological factors or reporting
      bias.

PMID- 18822024
TI  - A re-appraisal of lactose intolerance.
AB  - BACKGROUND: Lactose, beta-galactose-1,4-glucose, is hydrolysed by the enzyme
      lactase. Lactose intolerance occurs when lactase deficiency causes clinical
      symptoms. AIMS: To provide an overview of lactose intolerance, including
      definition, aetiology and epidemiology, the clinical symptoms and diagnostic
      testing and management. METHODS: A literature review was carried out to meet the
      aims of this paper. This resulted in the analysis of a database of patients
      tested for lactose intolerance to provide examples of the consequences of
      problems of terminology identified. CONCLUSIONS: The terminology relating to
      lactose intolerance is confusing for clinicians and researchers. Clinicians need
      to ensure that these problematic terms do not cause diagnostic mistakes and
      inappropriate treatment. Researchers should be aware of inconsistent terminology
      in studies and resultant problems with the interpretation of results.

PMID- 18822025
TI  - A meta-analysis of the vascular-related safety profile and efficacy of alpha
      adrenergic blockers for symptoms related to benign prostatic hyperplasia.
AB  - OBJECTIVES: To evaluate the safety profile and efficacy of alpha1-adrenergic
      receptor blockers (A1Bs) currently prescribed for benign prostatic hyperplasia
      (BPH). DATA SOURCES: A systematic literature search of MEDLINE, the Cochrane
      Database and the Food and Drug Administration Web site through December 2006
      identified double-blinded, prospective, placebo-controlled trials, evaluating
      agents commercially available by prescription for the symptomatic treatment of
      BPH. REVIEW METHODS: Data were reviewed by two investigators with the use of a
      standardised data abstraction form. Studies were evaluated for methodological
      quality using the Jadad scale. Studies with a score of < 3 were considered of
      weaker methodology. RESULTS: Of 2389 potential citations, 25 were usable for
      evaluation of safety data, 26 for efficacy. A1B use was associated with a
      statistically significant increase in the odds of developing a vascular-related
      event [odds ratio (OR) 2.54; 95% confidence interval (CI): 2.00-3.24; p <
      0.0001]. The odds of developing a vascular-related adverse event were: alfuzosin,
      OR 1.66, 95% CI: 1.17-2.36; terazosin, OR 3.71, 95% CI: 2.48-5.53; doxazosin, OR
      3.32, 95% CI: 2.10-5.23 and tamsulosin, OR 1.42, 95% CI: 0.99-2.05. A1Bs
      increased Q(max) by 1.32 ml/min (95% CI: 1.07-1.57) compared with placebo.
      Difference from placebo in American Urological Association symptom
      index/International Prostate Symptom Score was -1.92 points (95% CI: -2.71 to 
      1.14). CONCLUSIONS: Alfuzosin, terazosin and doxazosin showed a statistically
      significant increased risk of developing vascular-related events compared with
      placebo. Tamsulosin showed a numerical increase that was not statistically
      significant. All agents significantly improved Q(max) and symptom signs compared
      with placebo.

PMID- 18822026
TI  - Optimal time to take once-daily oral medications in clinical practice.
AB  - Currently only a few package inserts of once-daily medications specially define
      the dosing time, although sporadic studies have demonstrated administration time
      dependent effects on the therapeutic outcome. Some chronotherapeutic approaches
      aim to diminish the occurrence of adverse drug reactions (ADRs) and hence better
      tolerance and medication compliance whereas most of the chronotherapies are
      recommended to improve therapeutic efficacy. The administration time-dependent
      efficacy seems not a common feature of drugs within the similar therapeutic or
      structural class and it is related to kinds of drugs, pathophysiologic status,
      clinical symptoms and feedback from patients. Doctors, pharmacists and nurses
      should know what kind of drug has requirement for optimal dosing time, and
      realize that better efficacy and lower incidence of ADRs may be achieved by
      rational arrangement of administration schedule. In order to promote medication
      compliance, it is essential to provide patient education regarding differences
      between conventional and chronotherapeutic approaches and pathophysiologic
      benefits of chronotherapy.

PMID- 18822027
TI  - Blood pressure drug therapy and electrolyte disturbances.
AB  - Antihypertensive pharmacologic treatment may be associated with diverse
      disturbances of electrolyte homeostasis. These drug-induced disorders are
      relatively common, typically including hyponatraemia, hypokalaemia,
      hyperkalaemia, hypomagnesaemia, hypophosphataemia and hypercalcaemia. Diuretics,
      beta-blockers, angiotensin-converting enzyme inhibitors and angiotensin receptor
      blockers are particularly likely to cause these complications. Recognised risk
      factors include high-dosage regimens (especially diuretics), old age, diabetes
      and impairment of renal function. Strategies to prevent these adverse drug
      reactions involve careful consideration of risk factors and clinical and
      laboratory evaluation in the course of treatment.

PMID- 18822028
TI  - Diagnosis and management of Parkinson's disease dementia.
AB  - Parkinson's disease (PD) has long been considered predominantly a motor disorder.
      However, its frequent association with dementia, which contributes significantly
      to the morbidity and mortality of the condition, is gaining increasing
      recognition. PD dementia (PDD) has a unique clinical profile and neuropathology,
      distinct from Alzheimer's disease (AD). Cholinergic deficits, a feature of both
      AD and PDD, underlie the rationale for cholinesterase inhibitor therapy in both
      conditions. In clinical practice, it is important that PDD should be recognised
      and appropriately treated. This review aims to outline the recently proposed
      clinical diagnostic criteria for PDD and to summarise the
      guidelines/recommendations published since 2006 on the use of cholinesterase
      inhibitors in the management of PDD. Although the cholinesterase inhibitor
      rivastigmine has recently been approved for the management of PDD, there remains
      a need for the development of novel therapies that can affect key mechanisms of
      the disease or prevent/delay patients with PD and mild cognitive impairment from
      progressing to PDD.

PMID- 18822029
TI  - Overactive Bladder and Continence Guidelines: implementation, inaction or
      frustration?
AB  - Guidelines for the management of continence and overactive bladder are generally
      available across Europe. For a majority of countries, these have been adopted by
      professional societies in either urology or gynaecology for local use. There has,
      however, been little monitoring of formal implementation of these guidelines and
      seldom any attempt to audit their operation. The state of continence care
      therefore remains largely unknown. This article reviews current guidelines and
      their status across Europe and examines what might be relevant from other disease
      areas to promote successful implementation.

PMID- 18822030
TI  - Global experiences with vardenafil in men with erectile dysfunction and
      underlying conditions.
AB  - OBJECTIVE: Vardenafil has demonstrated efficacy for the pharmacological
      management of erectile dysfunction (ED). Accumulating evidence suggests that ED
      is frequently associated with underlying cardiovascular and metabolic conditions
      which are thought to be involved in the aetiology of ED. The present review aims
      to summarise and discuss the available evidence for the efficacy, safety and
      tolerability of vardenafil in patients with underlying conditions including
      diabetes, hypertension and dyslipidaemia. METHODS: Relevant articles were
      identified through a PubMed search of clinical trials and postmarketing
      surveillance studies of vardenafil in patients with ED including those with
      diabetes, hypertension and dyslipidaemia. RESULTS: Across all trials, vardenafil
      showed good efficacy for the treatment of ED in patients with diabetes,
      hypertension and dyslipidaemia. Vardenafil also showed a favourable safety and
      tolerability profile. The concomitant use of medication to treat hypertension or
      dyslipidaemia was not associated with an increase in adverse events following
      vardenafil treatment. CONCLUSIONS: The prevalence of both diagnosed and
      undiagnosed underlying conditions is high among men with ED. The evidence
      presented in this review suggests that vardenafil is efficacious and well
      tolerated in patients with ED and diabetes, hypertension and/or dyslipidaemia and
      can be recommended as first-line treatment for ED in patients with these
      conditions.

PMID- 18822031
TI  - Chest drains: always carefully evaluate the chest radiograph and patient.

PMID- 18822032
TI  - The impact of the menopausal transition on the body composition and abdominal fat
      distribution in middle-aged women: a study by bio-electrical impedance and
      computed tomography.

PMID- 18822033
TI  - Severe hypocalcaemia because of osteoblastic prostate carcinoma metastases.

PMID- 18822034
TI  - Suspicious breast mass in an anticoagulated patient--is core biopsy safe?

PMID- 18822035
TI  - Psychoflexed hand: a forgotten entity. A case report and review of the
      literature.

PMID- 18822036
TI  - A review of ageing and an examination of clinical methods in the assessment of
      ageing skin. Part I: Cellular and molecular perspectives of skin ageing.
AB  - The ageing process is noticeable within all organs of the body and manifests
      itself visibly in the skin. Skin ageing is influenced by several factors
      including genetics, environmental exposure, hormonal changes and metabolic
      processes. Together these factors lead to cumulative alterations of skin
      structure, function and appearance. The functioning of the central nervous,
      immune, endocrine and cardiovascular systems, as well as the skin is also
      impaired with age. Chronologically, aged skin is thin, relatively flattened, dry
      and unblemished, with some loss of elasticity and age-related loss of
      architectural regularity. General atrophy of the extracellular matrix is
      reflected by a decrease in the number of fibroblasts. Reduced levels of collagen
      and elastin, with impaired organization are primarily because of decreased
      protein synthesis affecting types I and III collagen in the dermis, with an
      increased breakdown of extracellular matrix proteins. Oxidative stress is
      considered of primary importance in driving the ageing process. The original free
      radical theory of ageing purported that the molecular basis of ageing was derived
      from a lifetime accumulation of oxidative damage to cells resulting from excess
      reactive oxygen species (ROS) produced as a consequence of aerobic metabolism.
      Although the skin possesses extremely efficient anti-oxidant activities, during
      ageing, ROS levels rise and anti-oxidant activities decline. The ROS are
      necessary in multiple MAP kinase pathways and the induction of AP-1, in turn, up
      regulates expression of matrix-metalloproteinases providing a plausible mechanism
      for the increased collagen degradation in aged human skin.

PMID- 18822037
TI  - A review of ageing and an examination of clinical methods in the assessment of
      ageing skin. Part 2: Clinical perspectives and clinical methods in the evaluation
      of ageing skin.
AB  - With the advancement of skin research, today's consumer has increased access to
      technological information about ageing skin and hair care products. As a result,
      there is a rapidly increasing demand for proof of efficacy of these products.
      Recognizing these demands has led to the development and validation of many
      clinical methods to measure and quantify ageing skin and the effects of anti
      ageing treatments. Many of the current testing methods used to research and
      evaluate anti-ageing product claim to employ sophisticated instruments alongside
      more traditional clinical methods. Intelligent use of combined clinical methods
      has enabled the development of technologically advanced consumer products
      providing enhanced efficacy and performance. Of non-invasive methods for the
      assessment and quantification of ageing skin, there is a plethora of tools
      available to the clinical researcher as defined by key clinically observed ageing
      parameters: skin roughness and surface texture; fine lines and wrinkles; skin
      pigmentation; skin colour; firmness and elasticity; hair loss; and proliferative
      lesions. Furthermore, many clinical procedures for the evaluation of ageing skin
      treatments are combined with invasive procedures, which enable added-value to
      claims (such as identification and alteration of biochemical markers),
      particularly in those cases where perception of product effect needs additional
      support. As discussed herein, clinical methods used in the assessment of skin
      ageing are many and require a disciplined approach to their use in such
      investigations.

PMID- 18822038
TI  - The perception threshold measurement can be a useful tool for evaluation of
      sensitive skin.
AB  - Sensitive skin is characterized by subjective symptoms that are hard to quantify.
      However, a neurobiological approach could improve our understanding of the nature
      of skin sensitivity. In this study, we measured the sensory perception of well
      controlled electric currents on the skin that stimulated sensory nerve fibres
      such as the myelinated A fibre, A delta fibre and unmyelinated c-fibre. The
      sensory perception thresholds were obtained quantitatively from subjects with
      sensitive-prone skin and controls. Application of 0.075% capsaicin, known to
      stimulate the nociceptor c-fibre, was topically applied; then the sensory
      perception thresholds were measured to determine whether the exposure to
      nociceptive stimulation could affect the subsequent sensory perception. The
      results showed that the perception thresholds of skin sensitive-prone subjects
      were low for the c-fibre measurements at 5 Hz electric current stimulation.
      Furthermore, a wide variation in sensory perception was noted in the skin
      sensitive-prone subjects after topical application of capsaicin. In conclusion,
      the abnormal sensory perception in individuals with sensitive skin appears to be
      related to neurological instability, where c-fibre nociception plays a role.
      Thus, quantitative sensory perception threshold measurement was found to be a
      useful method for the identification of skin sensitive-prone subjects.

PMID- 18822039
TI  - Cocoa polyphenols and their influence on parameters involved in ex vivo skin
      restructuring.
AB  - Polyphenols in general are compounds that are known to promote health and have a
      preventive effect against various chronic diseases. The influence of cocoa
      polyphenols on skin, however, has scarcely been studied from a histological point
      of view. The aim of this study is to assess the influence of cocoa polyphenols on
      several indicators of skin elasticity and skin tonus, namely, glycosaminoglycans
      and collagen I, III and IV. This was carried out by using a model of ex vivo
      human skin explants maintained in survival, on which a cocoa polyphenol extract
      was applied. After processing by standard histological techniques (fixation,
      paraffin embedding, sectioning, staining, immunostaining and microscopical
      observation), the influence of cocoa polyphenols on the evaluated parameters was
      quantified by image analysis. The results obtained show that cocoa polyphenols
      exhibit a positive action on the parameters assessed, and the dose at which they
      improve the most parameters associated with skin tonus and elasticity was
      determined. Their activity was compared with a commercially available product,
      and the results obtained show that their efficacy is equivalent. Moreover, an
      enhancing effect of cocoa butter on activity of cocoa polyphenol was highlighted.
      Now that the properties of cocoa polyphenols on ex vivo skin restructuring
      parameters have been assessed, the next step could include their evaluation in
      vivo.

PMID- 18822040
TI  - Properties of a new hydrotrope hydrophobic molecule and its potential
      applications.
AB  - In the present contribution, the properties of dipropylene glycol isobornyl ether
      (Pribelance) are discussed, especially in the context of microemulsion and
      emulsion formulations. Pribelance is a new low-toxic anti-foaming hydrotrope with
      excellent co-surfactant properties that has some similarities with long-chain
      alcohols, but in contrast to them, it is liquid at room temperature. In
      combination with another, more hydrophilic co-surfactant, it allows significant
      amounts of oil to be solubilized in water. Possible applications such as in
      cosmetics, as an anti-foaming agent or as additive to cooling lubricants are
      discussed. Further potential applications are plasticizers, fermentation systems,
      agrochemicals and waste-water treatments.

PMID- 18822041
TI  - Screening of Nepalese crude drugs traditionally used to treat hyperpigmentation:
      in vitro tyrosinase inhibition.
AB  - South-East Asian population is daily exposed to strong sunlight. As a result, the
      majority of population will have darker, ethnic skin. Moreover, many people
      suffer from dark spots, hyperpigmentation, which is considered to be a skin
      disorder and causes psychological disturbance. To treat dark spots, most of the
      population will still rely on traditionally used crude drugs, knowledge about
      which is transferred from generation to generation. Fifty-two crude drugs were
      selected based on the survey performed among local healers and beauticians of
      different ethnic origin. These crude drugs were screened for mushroom tyrosinase
      inhibitory activity, as tyrosinase inhibitors are becoming increasingly important
      as cosmetic and medicinal products, primarily to control hyperpigmentation. Among
      the tested crude drugs, methanolic extracts of Glycyrrhiza glabra, Morus alba,
      Syzygium aromaticum, Citrus aurantifolia, Cypreae moneta, Punica granatum and
      Citrus aurantium, at the final concentration of 50 microg mL(-1), showed mushroom
      tyrosinase inhibitory activity of 78.9%, 71.0%, 69.4%, 59.0%, 56.0%, 53.4 and
      51.9%, respectively, with 91.4% inhibitory activity of kojic acid taken as
      positive control. To our knowledge, this is the first report that extracts of
      Cypreae moneta shell and Syzygium aromaticum flowering bud have tyrosinase
      inhibitory activity. These potent extracts were further evaluated at different
      concentration. The final concentration of the extracts in reaction mixtures was
      50, 25 and 5 microg mL(-1) for the initial concentration of 1000, 500 and 100
      microg mL(-1), respectively. They showed concentration-dependent inhibition of
      mushroom tyrosinase. Those extracts expressing relatively weak tyrosinase
      inhibitory activity may act through different inhibition pathway which is not
      based on tyrosinase activity. Further evaluation of the most potent tyrosinase
      inhibitors in in vivo conditions would be recommended.

PMID- 18822042
TI  - Adaptation of the protocol for determining in vitro the sun protection factor of
      anti-solar sticks.
AB  - Apart from the protection offered by clothing, the application of sunscreen
      products suited to each type of skin constitutes one way for decreasing the
      frequency of skin cancers nowadays. After having adapted an in vitro method for
      determining the efficacy of sunscreens in emulsion form, we wished to transpose
      this technique by adapting it for the anti-solar sticks for the evaluation of sun
      protection factor (SPF) using a spectrophotometer equipped with an integrating
      sphere. To do this, we tested 14 products in the market as well as sticks that we
      ourselves fabricated in the laboratory. In a base common to all of these sticks,
      we added organic (13 filters tested) and inorganic (two filters tested, titanium
      dioxide and zinc oxide) to their maximum permitted concentration in the European
      Union. In parallel, emulsions containing the same filters at the same percentage
      of use were studied; to be in keeping with the results on the products packaging
      on the one hand, and with the results obtained for the emulsion form on the other
      hand, we were able to determine the optimal mass which needed to be placed on the
      support used the in vitro test to determine the SPF.

PMID- 18822043
TI  - Simultaneous determination of 21 preservatives in cosmetics by ultra performance
      liquid chromatography.
AB  - An ultra performance liquid chromatography (UPLC) method has been developed for
      the simultaneous determination of 21 preservatives: 2-methyl-4-isothiazoline-3
      ketone, bronopol, 5-chloro-2-methyl-4-isothiazoline-3-ketone, benzyl alcohol, 2
      phenoxyethanol, methyl-p-hydroxy benzoate, ethyl-p-hydroxy benzoate, methyl
      benzoate, 4-hydroxybenzoic acid iso-propyl ester, propyl-p-hydroxy benzoate, 4
      chloro-3-methylphenol, ethyl benzoate, 2-phenylphenol, 4-hydroxybenzoic acid iso
      butyl ester, butyl-p-hydroxy benzoate, 4-chloro-3,5-dimethylphenol, phenyl
      benzoate, 2,4-dichloro-3,5-dimethylphenol, 2-benzyl-4-chlorophenol, triclocarban
      and triclosan in cosmetics. A Waters ACQUITY UPLC BEH C(18) column was used with
      0.1% formic acid solution as the mobile phase under the condition of gradient
      elution. Preservatives were extracted with methanol by ultrasonicator, and then
      they were analysed by UPLC-PDA detector. All these preservatives were baseline
      separated in 8.5 min. The pre-treatment method of samples and the chromatographic
      condition of analysis were critically examined in this study. The recoveries
      ranged from 90.5 to 97.8%, with RSD values below 3.2%, and all correlation
      coefficients (r) were no less than 0.9997. Thus, this method could be used for
      analysing the preservatives in cosmetic products.

PMID- 18822044
TI  - Validation of HPLC method for quantitative determination of Tinosorb S and three
      other sunscreens in a high protection cosmetic product.
AB  - A chromatographic method (high performance liquid chromatography) with a diode
      array detector was developed for simultaneous assay of Tinosorb S (bis
      ethylhexyloxyphenol methoxyphenyl triazine) with three other sunscreen agents
      [benzophenone-3, butyl methoxydibenzoylmethane (avobenzone) and ethylhexyl
      methoxycinnamate] in high protection sunscreen. Separations were performed on a
      RP-18 Nucleodur Gravity column (150 x 4.6 mm, 5 mum) eluted with a ternary
      gradient mixture constituted of tetrahydrofuran, acetonitrile and an aqueous
      solution of acetic acid. The quantitative analysis was achieved with internal
      calibration performed with octyl dimethyl para-aminobenzoate (PABA) at 330 nm. In
      accordance with the analytical references (SFSTP, ICH, ISO...), the accuracy of
      the method was evaluated using a statistical approach of the validation
      parameters (specificity, response function, linearity, precision and trueness).
      For each studied ultraviolet filter, an accuracy profile was determined on a
      predicted range. These profiles show a graphical representation of the recovery
      percentage and confidence limits centred on 100%. The method is validated and can
      be used for analysis in cosmetic sunscreen products.

PMID- 18822060
TI  - ICSH guidelines for the standardization of bone marrow specimens and reports.
AB  - The bone marrow examination is an essential investigation for the diagnosis and
      management of many disorders of the blood and bone marrow. The aspirate and
      trephine biopsy specimens are complementary and when both are obtained, they
      provide a comprehensive evaluation of the bone marrow. The final interpretation
      requires the integration of peripheral blood, bone marrow aspirate and trephine
      biopsy findings, together with the results of supplementary tests such as
      immunophenotyping, cytogenetic analysis and molecular genetic studies as
      appropriate, in the context of clinical and other diagnostic findings. Methods
      for the preparation, processing and reporting of bone marrow aspirates and
      trephine biopsy specimens can vary considerably. These differences may result in
      inconsistencies in disease diagnosis or classification that may affect treatment
      and clinical outcomes. In recognition of the need for standardization in this
      area, an international Working Party for the Standardization of Bone Marrow
      Specimens and Reports was formed by the International Council for Standardization
      in Hematology (ICSH) to prepare a set of guidelines based on preferred best
      practices. The guidelines were discussed at the ICSH General Assemblies and
      reviewed by an international panel of experts to achieve further consensus.

PMID- 18822061
TI  - Nevi with site-related atypia: a review of melanocytic nevi with atypical
      histologic features based on anatomic site.
AB  - A subset of melanocytic nevi share features with melanoma and nevi with
      architectural disorder but are biologically inert and to date do not appear to
      portend an increased risk for the development of malignancy. These benign nevi
      with certain atypical histologic features cluster among specific anatomic sites
      and are thus designated nevi with site-related atypia. We categorize these
      lesions into four main groups: acral, genital, special site and conjunctival,
      based on anatomy and relative prevalence of specific atypical histologic
      features. As the literature and our recognition of these lesions continue to
      grow, our understanding of their biology has not kept pace.

PMID- 18822062
TI  - CD4+/CD56+ hematodermic neoplasm (blastic NK-cell lymphoma).

PMID- 18822063
TI  - School lunches: a continuing opportunity for dietitians.

PMID- 18822064
TI  - Development of a recommended food intake pattern for healthy Danish adolescents
      consistent with the Danish dietary guidelines, nutrient recommendations and
      national food preferences.
AB  - BACKGROUND: Danish adolescents have poor dietary habits compared to current
      recommendations. The present study aimed to develop a recommended food intake
      pattern for adolescents consistent with Danish Dietary Guidelines (DDG), Nordic
      Nutrition Recommendations (NNR) and dietary preferences. METHODS: The nutrient
      content of a food intake pattern consistent with DDG was calculated using dietary
      intake data from a random sample of 11-15-year-old boys (n = 85) and girls (n =
      70). A recommended food intake pattern was modelled to meet NNR. The
      discretionary energy allowance was calculated as the difference between the total
      energy level and the energy needed to meet recommended nutrient needs. The
      flexibility of the recommended food intake pattern was tested against various
      energy requirements and with the inclusion of basic foods with higher sugar
      and/or fat content. RESULTS: The developed food intake pattern meets all nutrient
      goals except for vitamin D. At low energy requirements, the intake of iron and
      selenium is of concern. To fulfil nutrient recommendations, half of the
      bread/cereals and vegetables consumed should be fibre-rich, and fats should be of
      plant origin. CONCLUSIONS: The recommended food intake pattern meets most
      nutrient recommendations and makes it possible to advise on discretionary energy.

PMID- 18822065
TI  - Re: Habitual caffeine intake in women of childbearing age.

PMID- 18822073
TI  - Editor's report: reflections on the first year.

PMID- 18822072
TI  - An oro-facial disease 'noma (cancrum oris)' in a Japanese monkey (Macaca
      fuscata): clinical signs, clinicopathological features, and response to
      treatment.
AB  - BACKGROUND: A Japanese monkey developed severe oro-facial lesions that were
      called noma in humans. Although extensive destruction of both the buccal regions
      occurred with rapid progress, author successfully treated the lesions with
      povidone-iodine, enrofloxacin, chymotrypsin, a glycyrrhizin preparation, and a
      basic fibroblast growth factor. METHODS: Author clinicopathologically
      investigated this disease during the treatment. RESULTS: In the subcutaneous and
      muscular tissues, the lesions developed characteristic changes such as dissolving
      collagen fibers and muscular tissues phagocytosed by giant and epitheloid cells.
      The monkey showed a notable increase in creatine kinase activities. The present
      examinations revealed severe invasive findings in muscular tissues, which were
      accompanied by infections of beta-hemolytic streptococcus Group C. This monkey
      was negative for simian immunodeficiency virus antibody; however, infection with
      simian D retrovirus was not ruled out. CONCLUSIONS: Simian noma was a rapidly
      devastating disease, which destroyed the muscle tissues of oro-facial structure.
      Nonhuman primates are the only species that develop oro-facial lesions,
      corresponding to noma in humans.

PMID- 18822074
TI  - Metastatic hepatocellular carcinoma: when, how, where and so what?

PMID- 18822075
TI  - Deciding liver transplant candidacy: tools of the trade.

PMID- 18822076
TI  - Pregnancy and liver transplantation.
AB  - Since the first pregnancy in a transplant recipient in 1958, pregnancy in
      recipients of solid organ transplants has become increasingly common. Although
      previously considered a hazardous event, data collected over the last 50 years
      demonstrate that despite an increased risk of maternal and fetal complications,
      pregnancy in transplant recipients can have a successful outcome. As of 2006,
      there were over 3000 female liver transplant recipients of childbearing age in
      the USA. Two hundred and two pregnancies and 205 outcomes were reported in 121
      liver transplant recipients in the National Transplantation Pregnancy Registry.
      Children born to female liver recipients have a greater risk of prematurity and
      low birth weight than the general population, but no malformation patterns have
      been observed. Mothers are more likely to experience pregnancy-induced
      hypertension, pre-eclampsia and caesarian section, but overall mortality is not
      worse. Rates of acute rejection and graft loss are similar to nonpregnant liver
      recipients. The optimal timing of conception post-transplant is controversial,
      but current recommendations suggest waiting for at least 1 year after
      transplantation. Choice of contraception is also debatable, although barrier
      methods have traditionally been preferred. Many medications used for post
      transplant immunosuppression have potential effects during pregnancy and breast
      feeding. The risks and benefits of each medication should be reviewed with
      patients contemplating pregnancy, and regimens should be tailored accordingly.

PMID- 18822077
TI  - Report from South Korea.

PMID- 18822078
TI  - Adult liver transplant survey: policies towards eligibility criteria in Canada
      and the United States 2007.
AB  - GOALS: To assess the current practice patterns of liver transplant centres in
      Canada and the USA regarding transplant eligibility. BACKGROUND: Liver
      transplantation is an evolving field and today remains the only life-sustaining
      treatment for end-stage liver disease. Issues of allocation and transplant
      eligibility are important factors in the ethical practice of medicine. STUDY:
      Questionnaires were mailed to liver transplant programme directors in Canada and
      the USA inquiring about current practices regarding recipient eligibility.
      RESULTS: This study demonstrates that there is consensus in the use of other
      eligibility criteria, including non-compliance, social status, abstinence from
      alcohol and methadone and cocaine use. Interestingly, literature is lacking to
      support the use of these parameters as eligibility criteria with the exception of
      alcohol. There is a lack in consensus regarding marijuana use, human
      immunodeficiency virus status, ability to accept blood transfusions and prisoner
      status. The literature suggests that liver transplantation in select patients who
      refuse blood transfusions results in good outcomes. CONCLUSIONS: Important
      decisions regarding transplant eligibility still have to be made empirically in
      the absence of scientific literature about various social issues. While consensus
      among transplant programmes is useful, it is important that we continue to use
      the evidence in the literature to revise these eligibility criteria, keeping in
      mind ethical principles applied to the access and allocation of a scarce
      resource.

PMID- 18822080
TI  - A taxonomic study on erysipelothrix by DNA-DNA hybridization experiments with
      numerous strains isolated from extensive origins.
AB  - The purpose of this study was to clarify the taxonomic relationship between all
      the serovars and species of the genus Erysipelothrix by performing DNA-DNA
      hybridization experiments, the customary criterion for separation of bacterial
      genospecies. A total of 93 strains were isolated from a wide variety of sources,
      including pigs affected with acute or chronic erysipelas, other diseased animals,
      healthy animals, fish, retail meats, and environmental materials from throughout
      the world during the period 1958 to 1996. The present data on phenotypic
      characterization and DNA relatedness values demonstrate that 24 strains (96%) of
      E. tonsillarum are avirulent for swine, whereas 39 strains (66%) of genomic E.
      rhusiopathiae induced generalized or local urticarial lesion in swine after
      intradermal inoculation. This observation suggests that genomic E. tonsillarum
      has little etiological significance. Three minor groups contained several strains
      which exhibited minimal association with each type strain of E. rhusiopathiae and
      E. tonsillarum. In conclusion, it was confirmed that members of the E.
      rhusiopathiae and E. tonsillarum groups resemble each other in regard to many
      phenotypic characteristics, but differ in their ability to produce acid from
      saccharose and in their pathogenicity for swine. The genus Erysipelothrix
      certainly contains two main species: E. rhusiopathiae and E. tonsillarum.

PMID- 18822081
TI  - Identification of the repeated number of C and D regions of tyrosine
      phosphorylation motifs in Helicobacter pylori cagA using multiplex PCR.
AB  - Various tyrosine phosphorylation motif regions of H. pylori cagA exist. The
      number of these regions was found to have some influence on cell signaling, which
      was found to be more pronounced when in D (ESS) region than in C (WSS) region. A
      molecular biological method with multiplex PCR was developed to distinguish C and
      D regions, and to identify the repetition number of tyrosine phosphorylation of
      the cagA gene. Multiplex PCR using novel primer sets was performed on 73 strains
      of H. pylori isolated from Korean patients with upper gastrointestinal diseases.
      The Western cagA was identified in only 3 strains (4.1%) whereas East Asia cagA
      was identified in 69 strains (94.5%). These results were reconfirmed through a
      sequencing analysis. The method developed in this study would be useful for
      monitoring the repeated number of C and D regions of tyrosine phosphorylation
      motifs in H. pylori cagA.

PMID- 18822082
TI  - Production and characterization of rabbit polyclonal sera against Shiga toxins
      Stx1 and Stx2 for detection of Shiga toxin-producing Escherichia coli.
AB  - STEC has emerged as an important group of enteric pathogens worldwide. In this
      study, rabbit polyclonal Stx1 and Stx2 antisera were raised and employed in the
      standardization of immunoassays for STEC detection. Using their respective
      antisera, the limit of detection of the toxin was 35.0 pg for Stx1 and 5.4 pg for
      Stx2. By immunoblotting, these antisera recognized both toxin subunits. Cross
      reactivity was observed in the A subunit, but only Stx2 antiserum was able to
      neutralize the cytotoxicity of both toxins in the Vero cell assay. Six stx
      harboring E. coli isolates were analyzed for their virulence traits. They
      belonged to different serotypes, including the O48:H7, described for the first
      time in Brazil. Only three strains harbored eae, and the e-hly gene and hemolytic
      activity was detected in five strains. Three isolates showed new stx2 variants
      (stx(2v-ha) and stx(2vb-hb)). The ELISA assay detected all six isolates,
      including one VCA-negative isolate, while the immunodot assay failed to detect
      one isolate, which was VCA-positive. In contrast, the colony-immunoblot assay
      detected only one VCA-positive isolate. Our results demonstrate that among the
      immunoassays developed in this study, the immunodot, and particularly the ELISA,
      appear as perspective for STEC detection in developing countries.

PMID- 18822083
TI  - Diversity of laccase among Cryptococcus neoformans serotypes.
AB  - The pathogenic yeast C. neoformans is classified into three varieties with five
      serotypes; var. grubii (serotype A), var. neoformans (serotype D), var. gattii
      (serotypes B and C), and serotype AD. Melanin is a virulence factor in the
      species, and its biosynthesis is catalyzed by laccase, encoded by the LAC1 gene.
      In order to estimate the natural variability of the LAC1 gene among Cryptococcus
      serotypes, the laccase protein sequence from 55 strains was determined and the
      phylogenetic relationships between cryptococcal and related fungal laccases
      revealed. The deduced laccase proteins consisted of 624 amino acid residues in
      serotypes A, D and AD, and 613 to 615 residues in serotypes B and C. Intra
      serotype amino acid variation was marginal within serotypes A and D, and none was
      found within serotypes AD and C. Maximum amino acid replacement occurred in two
      serotype B strains. The similarity in the deduced sequence ranged from 80 to 96%
      between serotypes. The sequence in the copper-binding regions was strongly
      conserved in the five serotypes. The laccases of the five serotypes were grouped
      together in the same clade of the phylogenetic tree reconstructed from different
      fungal laccases, suggesting a monophyletic clade.

PMID- 18822084
TI  - Decreased interferon-alpha production and impaired regulatory function of
      plasmacytoid dendritic cells induced by the hepatitis C virus NS 5 protein.
AB  - pDC are known to produce large amount of IFN-alpha/beta in response to viruses,
      and act as a major link between the innate and adaptive immune response. This
      study concentrated on the interaction of human peripheral blood derived pDC with
      HCV NS3, NS4, and NS5 proteins, and their maturation, cytokine secretion and
      functional properties. It was shown that HCV NS5 interferes with CD40L induced
      maturation of pDC as indicated by decreased expression of CD83 and CD86 markers.
      CpG ODN stimulated HCV NS3 and NS5 treated pDC showed decreased production of IFN
      alpha. In the case of NS3, IFN-alpha production was reduced to 126 pg/ml as
      compared to 245 pg/ml in controls (P < 0.01), and with NS5, IFN-alpha production
      was reduced to 92 pg/ml as compared to 238 pg/ml in controls (P < 0.05). In the
      presence of HCV NS5, the T cell stimulatory capacity of pDC was impaired, as
      indicated by decreased proliferation of T cells, and decreased production by the
      T cells of IFN-gamma, which were down to 86 pg/ml as compared to 260 pg/ml in
      controls (P < 0.05). These results suggest that HCV NS5 impairs pDC function and
      is in agreement with several other in vivo studies indicating decreased numbers
      of, and dysfunctional pDC, in chronic HCV infected patients.

PMID- 18822085
TI  - Isolation of tetracycline-resistant clinical Helicobacter pylori without
      mutations in 16S rRNA gene in Bangladesh.
AB  - The occurrence of 16S rRNA gene mutations associated with resistance to
      tetracycline in H. pylori isolated in Bangladesh was investigated. Tetracycline
      susceptibility was determined by the agar dilution method. The 16S rRNA genes of
      these isolates were sequenced and analyzed. A tetracycline accumulation assay was
      performed. DNA sequence and transformation tests of nine tetracycline-resistant
      (MIC = 2 microg/ml) Bangladeshi H. pylori clinical isolates showed that in no
      case was the resistance due to mutations in the 16S rRNA gene, the only known
      cause of tetracycline resistance in this pathogen. Tetracycline accumulation
      assays implicated altered uptake or efflux.

PMID- 18822086
TI  - Paraneoplastic antibody during follow-up of a patient with anti-Ri-associated
      paraneoplastic neurological syndrome.
AB  - BACKGROUND: The role of classical antineuronal antibody determinations to confirm
      the paraneoplastic aetiology of a neurological syndrome is well established.
      However, the value of antineuronal antibody estimation during follow-up of
      paraneoplastic neurological syndromes (PNS) is not known. AIMS OF THE STUDY:
      Prospective analysis of antibody concentrations in follow-up serum samples from a
      patient with anti-Ri-associated PNS. METHODS: Semiquantitative estimation of
      antibody concentrations with an ELISA using recombinant Ri antigen. RESULTS:
      Semiquantitative estimation of circulating anti-Ri antibodies demonstrated a
      renewed increase in antibody levels preceding relapse of the cancer, as confirmed
      using F-fluorodeoxyglucose positron emission tomography (FDG-PET). CONCLUSIONS:
      This is the first prospective report on serial anti-Ri antibody determinations.
      As a large increase in antineuronal antibody concentrations in follow-up serum
      samples preceded relapse of the cancer, paraneoplastic antineuronal antibodies
      may represent a marker for tumour activity in this case. These results warrant
      further multicentre studies to investigate the ability of serial quantification
      of classical antineuronal antibodies in monitoring PNS and in predicting relapse
      of cancers.

PMID- 18822087
TI  - Comparison of apomorphine and levodopa infusions in four patients with
      Parkinson's disease with symptom fluctuations.
AB  - BACKGROUND: Motor fluctuations in patients with advanced Parkinson's disease may
      be successfully treated with subcutaneous apomorphine infusion or intraduodenal
      levodopa/carbidopa infusion. No comparative trials of these two alternatives were
      performed. AIMS OF THE STUDY: We present a subanalysis from a randomized
      crossover clinical trial where levodopa infusion as monotherapy was compared with
      any other combination of pharmacotherapy in fluctuating patients. Four patients
      used apomorphine infusion and oral levodopa in the comparator arm. The results of
      these four patients are presented in detail. METHODS: The duration of the trial
      was 3 + 3 weeks. Patients were video-recorded half-hourly on two non-consecutive
      days of both treatment arms. Blinded video ratings were used. Patient self
      assessments of motor function and quality-of-life (QoL) parameters were captured
      using an electronic diary. RESULTS: Ratings in moderate to severe "off" state
      ranged 0-44% on apomorphine infusion and 0-6% on levodopa infusion. Moderate to
      severe dyskinesias were not recorded in any of the treatments. QoL was reported
      to be improved in all patients on duodenal levodopa infusion. CONCLUSIONS:
      Monotherapy with duodenal infusion of levodopa was more efficacious and brought
      greater QoL than combination therapy with apomorphine infusion in these
      fluctuating patients.

PMID- 18822088
TI  - Adolescent Transition to Adult Care in Solid Organ Transplantation: a consensus
      conference report.
AB  - Transition of care from pediatric to adult-oriented health care providers is
      difficult for children with special health care needs. Children who have received
      solid organ transplants and their providers experience the same difficulties and
      frustrations as children with other major illnesses. A consensus conference was
      organized by several transplant organizations to identify major issues in this
      area and recommend possible approaches to easing the process of transition for
      solid organ transplant recipients. This report summarizes the discussions and
      recommendations.

PMID- 18822089
TI  - Subjective and objective sleep among depressed and non-depressed postnatal women.
AB  - OBJECTIVE: Women sleep less in the postnatal period and it has been suggested
      that mothers diagnosed with depression alternatively could be suffering from the
      effects of chronic sleep deprivation. METHOD: From a population-based study, we
      recruited 42 women, of whom 21 scored >or=10 on the Edinburgh Postnatal
      Depression Scale. Sleep was registered by the Pittsburgh Sleep Quality Index
      (PSQI), sleep diaries and actigraphy 2 months after delivery. RESULTS: There were
      significant differences in subjective sleep measured retrospectively by the PSQI
      between depressed and non-depressed women. In contrast, there were no significant
      differences in sleep measured prospectively by sleep diaries and actigraphy. Both
      depressed and non-depressed women had impaired sleep efficiency (82%) and were
      awake for about 1.5 h during the night. Primipara had worse sleep, measured by
      actigraphy, compared with multipara. CONCLUSION: Measured objectively and
      prospectively, women with depression did not have worse sleep than non-depressed
      women.

PMID- 18822090
TI  - Group cognitive behavioural therapy for obsessive-compulsive disorder: a
      systematic review and meta-analysis.
AB  - OBJECTIVE: Behaviour therapy with exposure and response prevention (ERP) or
      cognitive behavioural therapy (CBT) including ERP are considered the
      psychological treatments of choice for obsessive-compulsive disorder (OCD), but
      group CBT/ERP has received relatively little research attention in the treatment
      of OCD. The aim of this study was to provide a meta-analysis of the effectiveness
      of group CBT/ERP for OCD. METHOD: A systematic literature search was conducted
      and studies were meta-analysed by means of the Cochrane Review Manager Program
      with measures of i) pre- to post-effect sizes (ES) and ii) between-group ES in
      comparison with different control conditions. Outcome was primarily measured on
      the Y-BOCS and ES was calculated in the form of Cohens d. RESULTS: Thirteen
      trials were included in the meta-analysis. The overall pre-post-ES of these
      trials of 1.18 and a between-group ES of 1.12 compared with waiting list control
      in three randomized controlled studies indicate that group CBT/ERP is an
      effective treatment for OCD. Group CBT achieved better results than
      pharmacological treatment in two studies. One study found no significant
      differences between individual and group CBT. CONCLUSION: Group CBT is an
      effective treatment for OCD, but more studies are needed to compare the
      effectiveness of group and individual treatment formats.

PMID- 18822091
TI  - Preterm birth or foetal growth impairment and psychiatric hospitalization in
      adolescence and early adulthood in a Swedish population-based birth cohort.
AB  - OBJECTIVE: Preterm birth and restricted foetal growth are related to symptoms of
      psychiatric disorder. Our aim was therefore to investigate possible relations
      between being born preterm and/or small for gestational age (SGA) and later
      psychiatric hospitalization. METHOD: A population-based registry study of
      psychiatric hospitalization of in total 155,994 boys and 148,281 girls born in
      Sweden in 1973-1975. RESULTS: The risk of hospitalization for all mental
      disorders was increased for preterm SGA boys (OR 2.19, 95% CI 1.49-3.21); at-term
      SGA boys (OR 1.55, 95% CI 1.34-1.79); at-term SGA girls (OR 1.31, 95% CI 1.15
      1.50). At-term SGA boys and girls suffered increased risk of anxiety and
      adjustment disorders (OR 1.70, 95% CI 1.18-2.45 and OR 1.49, 95% CI 1.14-1.94).
      Preterm SGA boys were at risk of personality disorders (OR 3.30, 95% CI 1.16
      9.41) and psychotic disorders (OR 4.36, 95% CI 1.85-10.30). CONCLUSION: The
      results show a relationship between being born SGA and later psychiatric
      hospitalization, where preterm birth and male gender seem to increase the risk.

PMID- 18822092
TI  - Does reactivity to stress cosegregate with subclinical psychosis? A general
      population twin study.
AB  - OBJECTIVE: This study assessed the relationship between stress reactivity (trait
      1) and psychosis (trait 2) across genetically related persons (cross-twin, cross
      trait design) to examine whether stress reactivity is an uncontaminated and
      unconfounded familial marker of psychosis risk. METHOD: Reactivity to stress and
      subclinical psychotic experiences were assessed in 289 female, general population
      twin-pairs. Cross-trait, within-twin associations investigating the association
      between stress reactivity and subclinical psychotic experiences in each person,
      were calculated. In addition, cross-trait, cross-twin associations were
      calculated to assess whether stress reactivity in one twin was moderated by
      subclinical psychotic experiences in the co-twin. RESULTS: Cross-trait, within
      twin analyses showed significant associations between stress reactivity and
      subclinical psychotic experiences in each person. In addition, the cross-trait
      cross-twin analyses showed that stress reactivity in twin 1 was significantly
      moderated by subclinical experiences in the co-twin. CONCLUSION: The results
      suggest that the psychosis phenotype cosegregates with increased emotional
      reactivity to stress in daily life.

PMID- 18822093
TI  - Accuracy of detecting changes in auditory heart rate in a simulated operating
      room environment.
AB  - The threshold for the identification of changes in heart rate and the accuracy in
      estimating heart rate were compared between 20 anaesthetists and 20 non
      anaesthetists in a simulated operating theatre, both with and without distraction
      tasks. Typical operating theatre distractions were simulated by requiring
      anaesthetists and non-anaesthetists to perform secondary tasks. There were no
      differences found between the groups in identification of heart rate changes. The
      distraction tasks reduced performance in both groups (to a greater extent in the
      anaesthetists group). A change of > 10 beats per minute was required for 80% of
      the changes to be detected. An upward heart rate change was more easily detected
      than a reduction. Anaesthetists were found to be marginally better at estimating
      the heart rate change from an auditory tone alone. However, the study did not
      confirm that anaesthetists have a superior ability to detect changes in heart
      rate than non-anaesthetists.

PMID- 18822094
TI  - Effects of propofol on pulmonary inflammatory response and dysfunction induced by
      cardiopulmonary bypass.
AB  - The pulmonary inflammatory response and pulmonary dysfunction after
      cardiopulmonary bypass is a major problem in patients undergoing cardiac surgery.
      Propofol has anti-inflammatory and immunomodulatory properties which may
      attenuate this response. Thirty patients undergoing cardiopulmonary bypass were
      randomly assigned to receive saline (control group) or propofol (propofol group).
      Pulmonary thoracic compliance, respiratory index, malondialdehyde and interleukin
      8 concentrations and intrapulmonary polymorphonucleocyte sequestration were
      measured at pre-bypass and 5, 30, 60, 90 and 120 min after unclamping the aorta.
      Plasma levels of interleukin-8, malondialdehyde and the respiratory index
      increased and reached peaks 30 min after unclamping in both groups. However, in
      the propofol group the increases were less than in the control group (p < 0.01).
      Intrapulmonary polymorphonucleocytes sequestration in the propofol group was less
      than in the control group 5 min after unclamping (p < 0.0001). Pulmonary thoracic
      compliance decreased significantly after unclamping in both groups, but the
      reduction was less in the propofol group (p < 0.01). These findings suggest that
      propofol administered during bypass could reduce the severity of pulmonary
      dysfunction.

PMID- 18822095
TI  - Use of heart rate variability analysis to determine the risk of cardiac ischaemia
      in high-risk patients undergoing general anaesthesia.
AB  - The aim of this study was to investigate the use of pre-operative heart rate
      variability analysis to predict postoperative cardiac events (identified by 24 h
      Holter-ECG recording and an increase of creatine kinase MB) in high-risk cardiac
      patients. Length of hospital stay, the incidence of postoperative cardiac
      ischaemia and cardiac events after discharge were recorded. Fifty patients were
      assigned by the presence of cardiac events and the heart rate variability in 17
      patients with an event was compared with 33 patients without. Total power was
      identified as a predictive parameter. The usefulness of this test was assessed in
      a second group of 50 patients. The incidence of cardiac events detected by Holter
      ECG recording or an increased creatine kinase MB was greater and the duration of
      hospital stay longer in the 26 patients with total power < 400 ms(2).Hz(-1)
      compared with those with total power > 400 ms(2).Hz(-1) (eight and four patients
      and 10 (7) days (mean (SD)), vs 1 (p < 0.05) and 0 (p < 0.05) patients and 6 (2)
      days (p < 0.05), respectively). The total power of high-risk cardiac patients
      predicted postoperative cardiac events and extended length of hospital stay.

PMID- 18822096
TI  - Associations between the 11-bp deletion in the myostatin gene and carcass quality
      in Angus-sired cattle.
AB  - An 11-bp deletion in the bovine myostatin (MSTN) gene was identified as the
      causative mutation for the double-muscling phenotype in Belgian Blue and
      Asturiana cattle. More recently, this mutation was also identified in the South
      Devon breed of cattle, in which it has been found to be associated with a general
      increase in muscle mass. The present study found that the mutant allele was also
      segregating in a commercial population of Scottish Aberdeen Angus beef cattle.
      The mutation was found at a low frequency (0.04) with no animals homozygous for
      the mutation in the sample population (536 animals). The effects of this mutation
      on various carcass traits of economic interest were then tested. We found that
      the mutation significantly increased carcass weight, sirloin weight, hindquarter
      weight, muscle conformation score and eye muscle area, but had no effect on the
      fat traits.

PMID- 18822097
TI  - A GYS1 gene mutation is highly associated with polysaccharide storage myopathy in
      Cob Normand draught horses.
AB  - Glycogen storage diseases or glycogenoses are inherited diseases caused by
      abnormalities of enzymes that regulate the synthesis or degradation of glycogen.
      Deleterious mutations in many genes of the glyco(geno)lytic or the glycogenesis
      pathways can potentially cause a glycogenosis, and currently mutations in
      fourteen different genes are known to cause animal or human glycogenoses,
      resulting in myopathies and/or hepatic disorders. The genetic bases of two forms
      of glycogenosis are currently known in horses. A fatal neonatal polysystemic type
      IV glycogenosis, inherited recessively in affected Quarter Horse foals, is due to
      a mutation in the glycogen branching enzyme gene (GBE1). A second type of
      glycogenosis, termed polysaccharide storage myopathy (PSSM), is observed in adult
      Quarter Horses and other breeds. A severe form of PSSM also occurs in draught
      horses. A mutation in the skeletal muscle glycogen synthase gene (GYS1) was
      recently reported to be highly associated with PSSM in Quarter Horses and Belgian
      draught horses. This GYS1 point mutation appears to cause a gain-of-function of
      the enzyme and to result in the accumulation of a glycogen-like, less-branched
      polysaccharide in skeletal muscle. It is inherited as a dominant trait. The aim
      of this work was to test for possible associations between genetic polymorphisms
      in four candidate genes of the glycogen pathway or the GYS1 mutation in Cob
      Normand draught horses diagnosed with PSSM by muscle biopsy.

PMID- 18822098
TI  - Characterization of the complete porcine MSTN gene and expression levels in pig
      breeds differing in muscularity.
AB  - Myostatin (MSTN), a transforming growth factor beta superfamily member, is an
      essential factor for the growth and development of muscle mass. The protein
      functions as a negative regulator of muscle growth and is related to the so
      called double-muscling phenotype in cattle, where a series of mutations renders
      the gene inactive. One particular breed of pigs, the Belgian Pietrain, also shows
      a heavily muscled phenotype. The similarity of muscular phenotypes between the
      double-muscled cattle and Pietrain pigs indicated that MSTN may be a candidate
      gene for muscular hypertrophy in pigs. In this study, we sequenced and analysed
      the complete MSTN gene from 45 pigs of five different breeds, including the
      heavily muscled Pietrain breed at one extreme and the Meishan and Wild boar
      breeds at the other extreme. In total, 7626 bp of the porcine MSTN gene were
      sequenced, including the 5' and 3' UTR. Fifteen polymorphic loci were found,
      three of which were located in the promoter region, five in intron 1 and seven in
      intron 2. Most mutations were found when comparing the obtained MSTN sequence
      with porcine MSTN sequences already published. However, one polymorphism located
      at position 447 of the porcine MSTN promoter had a very high allele frequency in
      the Pietrain pig breed and disrupted a putative myocyte enhancer factor 3 binding
      site. Real-time PCR using Sybr Green showed that this mutation was associated
      with expression levels of the MSTN gene in m. longissimus dorsi at an age of 4
      weeks.

PMID- 18822099
TI  - The effects of polymorphisms in the DGAT1, leptin and growth hormone receptor
      gene loci on body energy, blood metabolic and reproductive traits of Holstein
      cows.
AB  - The objective of this study was to examine the impact of polymorphisms in the
      acyl-CoA:diacylglycerol acyltransferase (DGAT1), leptin and growth hormone
      receptor genes on body energy (body condition score, total body energy content
      and cumulative effective energy balance) and blood metabolic traits (levels of
      beta-hydroxybutyrate, glucose and non-esterified fatty acids), measured once
      before the first calving and then repeatedly throughout first lactation in 497
      Holstein cows. The influence of the same polymorphisms on cow reproductive
      performance and health during the first and second lactations was also assessed.
      Several reproductive traits were considered including interval, conception and
      insemination traits, as well as incidence of metritis and reproductive problems.
      Genotyping was performed using PCR-RFLP (DGAT1, leptin) or allele-specific PCR
      (growth hormone receptor). For each locus, the effect of allele substitution on
      body energy and blood metabolic traits was estimated using random regression
      models. The same effect on reproductive traits was assessed with single-trait
      mixed linear models. Significant (P<0.05) effects on specific reproductive traits
      were observed. DGAT1 and growth hormone receptor alleles responsible for
      significant increases in milk production were found to have an adverse effect on
      reproduction, while the leptin allele responsible for significant increase in
      milk production was linked to marginally increased metritis frequency.
      Furthermore, the three studied loci were also found to significantly (P<0.05)
      affect certain body energy and blood metabolic traits. Several associations are
      published for the first time, but these should be confirmed by other
      investigators before the polymorphisms are used in gene-assisted selection.

PMID- 18822100
TI  - Albinism in the American mink (Neovison vison) is associated with a tyrosinase
      nonsense mutation.
AB  - Albino phenotypes are documented in various species including the American mink.
      In other species the albino phenotypes are associated with tyrosinase (TYR) gene
      mutations; therefore TYR was considered the candidate gene for albinism in mink.
      Four microsatellite markers were chosen in the predicted region of the TYR gene.
      Genotypes at the markers Mvi6025 and Mvi6034 were found to be associated with the
      albino phenotype within an extended half-sib family. A BAC clone containing
      Mvi6034 was mapped to chromosome 7q1.1-q1.3 by fluorescent in situ hybridization.
      Subsequent analysis of genomic TYR sequences from wild-type and albino mink
      samples identified a nonsense mutation in exon 1, which converts a TGT codon
      encoding cysteine to a TGA stop codon (c.138T>A, p.C46X; EU627590). The mutation
      truncates more than 90% of the normal gene product including the putative
      catalytic domains. The results indicate that the nonsense mutation is responsible
      for the albino phenotype in the American mink.

PMID- 18822101
TI  - Ancestral matrilineages and mitochondrial DNA diversity of the Lidia cattle
      breed.
AB  - To clarify the genetic ancestry and the mitochondrial DNA (mtDNA) diversity of
      the Lidia cattle breed, a 521-bp D-loop fragment was sequenced in 527 animals
      belonging to 70 herds distributed across 29 lineages. The mtDNA diversity
      recorded was similar to that seen for Middle Eastern breeds and greater than that
      recorded for the majority of European breeds. Haplotype T3 was the most common
      (81%), followed by the African T1 haplotype (17%); very low frequencies were
      recorded for haplotypes T and T2. The results agree with there being two major
      ancestral lines for the Lidia breed, European and African, similar to that seen
      for other Mediterranean breeds. A wide range of variation in haplotype
      frequencies was seen between the examined lineages. Haplotype T3 was present in
      all those analysed; in five it was the only one present, and in only one lineage
      (Miura) was its frequency lower than that of T1. T1*, a haplotype reported in
      Criollo breeds and to date in only a single European breed (the Retinta breed
      from Spain), was found in a single animal belonging to the Concha y Sierra
      lineage. Network analysis of the Lidia breed revealed the presence of two major
      haplotypes: T3 and T1. The Lidia breed appears to be more closely related to
      prehistoric Iberian and Italian than to British aurochs.

PMID- 18822102
TI  - Arterial anastomosis in a pediatric patient receiving a right extended split
      liver transplant: a case report.
AB  - We report a case of a pediatric patient who received a right-extended liver
      transplant. The size of the recipient hepatic artery did not match with the donor
      right hepatic arterial stump. Moreover, recipient arterial anatomy made the
      direct anastomosis difficult or at increased risk for complications. The
      recipient's splenic artery was then mobilized, divided and anastomosed to the
      donor's right hepatic artery. The spleen was preserved and revascularization
      through collaterals is demonstrated by Angio CT Scan. Doppler US of the
      transplanted liver demonstrated good flow through the liver and the patient was
      discharged with perfect liver function. Splenic artery is perfectly suited for
      hepatic artery anastomosis. The use of splenic artery is favored in particular
      situations as in the case of a pediatric recipient receiving a right-extended
      liver graft with small caliber artery.

PMID- 18822103
TI  - Clinical and genetic heterogeneity in Omenn syndrome and severe combined immune
      deficiency.
AB  - OS has been described as a clinical phenotype in infants characterized by SCID,
      diffuse erythroderma, and other distinct features. The pathogenesis is secondary
      to autologous, auto-reactive T cells produced as rare escapees from the SCID
      blockade. Mutations in either the RAG1 or RAG2 gene that lead to partial
      recombinase activity are responsible for many of the patients with these clinical
      features. We report on two patients, one with an atypical phenotype of OS
      (absence of rash but presence of other typical features) who harbored a
      previously undescribed mutation in RAG1, and a second who had many of the classic
      features of OS but was found to have a mutation in the common gamma chain
      (gamma(c)) cytokine receptor gene. These cases highlight the clinical and genetic
      heterogeneity of OS.

PMID- 18822104
TI  - Intrathecal chemoprophylaxis after HSCT in children.
AB  - At present, the literature on the efficacy and risks of i.t. chemotherapy to
      children after HSCT is scarce. Current practices to reduce the risk of leukemic
      relapse in the CNS after HSCT differ between centers of transplantation. We
      compared 74 patients (56 ALL/18 AML), who received i.t. therapy post-HSCT with 46
      patients (36 ALL/10 AML) who did not receive post-HSCT i.t. therapy. The patients
      were transplanted at the University Children's Hospital, Uppsala or the
      Karolinska University Hospital, Huddinge, two Swedish transplantation units with
      different routines concerning i.t. therapy after HSCT. The primary end-point was
      the number of isolated CNS relapses. Secondary end-points were other types of
      relapse, death, and neurological complications. There was no statistically
      significant difference in the incidence of CNS relapses between the groups (p >
      0.05). I.t. therapy did not reduce the overall incidence of isolated CNS relapse
      or mortality. Our study did not demonstrate a protective effect of i.t. therapy
      indicating that post-HSCT i.t. therapy may only be of limited use in the
      treatment of acute childhood leukemia. We conclude that with the risks present,
      i.t. therapy should be carefully evaluated, and only considered in high-risk
      cases.

PMID- 18822105
TI  - Successful allogeneic unrelated bone marrow transplantation using reduced
      intensity conditioning for the treatment of X-linked adrenoleukodystrophy in a
      one-yr-old boy.
AB  - The childhood cerebral form of X-linked ALD is a demyelinating disorder of the
      central nervous system, which rapidly leads to total disability and death.
      Allogeneic stem cell transplantation benefits patients who show early evidence of
      the demyelination. We report here a one-yr-old boy with ALD who received HLA
      matched unrelated BMT in an early stage of the disease after careful planning and
      observation since his birth. BMT was performed when MRI began to show slight
      signal intensity changes in the white matter of the brain. Pretransplant
      conditioning consisted of fludarabine, l-PAM and TBI (2 Gy). GVHD prophylaxis
      consisted of cyclosporine A and short-course methotrexate. The patient showed an
      uneventful BMT course with fast and stable engraftment. Following BMT, the plasma
      levels of VLCFA decreased gradually and MRI changes improved. The patient did not
      have any evidence of further neurological deterioration 22 months following the
      transplant. Although this is still a short follow-up, it has been shown that BMT
      should be considered when a child has a biochemical diagnosis and MRI findings of
      ALD without any neurological signs. RIST should be considered as a pretransplant
      conditioning for ALD.

PMID- 18822106
TI  - Intravenous immunoglobulin as rescue therapy for BK virus nephropathy.
AB  - BKVN has emerged as an important cause of pediatric renal allograft nephropathy,
      with significant graft dysfunction in majority of the cases. Reduced
      immunosuppression and cidofovir therapy are the most commonly used therapeutic
      options for the treatment of BKVN in these patients. Recently, a preliminary
      study in adult renal allograft recipients with BKVN showed a therapeutic response
      to a combined approach of immunosuppression reduction and IVIg administration. A
      therapeutic benefit of IVIg without another concomitant treatment intervention
      has not been evaluated. We report stabilization of renal functions, histological
      resolution of BKVN and significant reduction in BK viremia in pediatric renal
      transplant with the use of IVIg, after an inadequate response to
      immunosuppression reduction and cidofovir therapy. In addition, we review the
      current literature on the use of cidofovir in pediatric renal transplant patients
      with BKVN and the potential of IVIg use in this condition.

PMID- 18822107
TI  - Rituximab for post-transplant recurrences of FSGS.
AB  - A 14-yr-old boy whose primary kidney disease was FSGS developed severe recurrence
      of proteinuria immediately after a second living-related kidney transplant.
      Despite pre- and post-operative PP and immunosuppressive treatment consisting of
      steroids, CycA, daclizumab, and MMF, daily protein excretion and serum creatinine
      increased. We therefore administered rituximab on the fourth day of
      transplantation. He received four weekly doses of rituximab (375 mg/m(2)/dose),
      which resulted in a rapid clearing of circulating CD19-positive B cells, and
      remission of proteinuria was achieved six wk after the first rituximab treatment.
      Graft function was excellent six months after transplantation with proteinuria of
      8 mg/m(2)/h. We conclude that rituximab may be an effective treatment for post
      transplant recurrence of FSGS.

PMID- 18822108
TI  - Differential invasion of Trypanosoma brucei brucei and lymphocytes into the brain
      of C57BL/6 and 129Sv/Ev mice.
AB  - Trypanosoma brucei subspecies invade the brain parenchyma at late stages of human
      and experimental rodent infections. In this study, we compared the outcome of
      infection with T. b. brucei in MHC-matched (H-2b) C57BL/6 (B6) and 129Sv/Ev (Sv
      129). Sv-129 showed higher parasitaemia and lower specific IgM (but not IgG)
      antibody levels than B6 mice. The number of trypanosomes, CD4+ and CD8+ T cells
      in the brain parenchyma was higher in B6 mice. B6 mice lost weight and showed
      higher cumulative mortality when compared with Sv-129 mice. Higher levels of IL
      1beta, IL-6, IL-10, TNF-alpha, IFN-gamma, ICAM-1 and E-selectin, but low levels
      of TGF-beta mRNA were present in brains of B6 when compared with Sv-129-infected
      mice. Thus, host genetics differentially determine the invasion of T. b. brucei
      into the brain parenchyma, which is paralleled by the severity of inflammation in
      the brain and course of the disease, but not by parasitaemia nor by antibody
      titres.

PMID- 18822109
TI  - Effect of neonatal sublingual vaccination with native or denatured ovalbumin and
      adjuvant CpG or cholera toxin on systemic and mucosal immunity in mice.
AB  - Sublingual immunotherapy has been applied for allergic diseases, but whether
      sublingual immunization in neonates can prevent sensitization has not been
      studied. In this study, we evaluate the effect of neonatal sublingual vaccination
      with native or denatured allergens alone or plus adjuvant on allergy prevention.
      Newborn BALB/c mice were sublingually vaccinated daily for the first 3 days with
      native or denatured ovalbumin (OVA) only, or combined adjuvant CpG or cholera
      toxin (CT). They were sensitized with OVA adsorbed onto alum 7 weeks after the
      last vaccination. Specific secretory IgA antibody responses were readily induced
      by neonatal vaccination with antigen plus CpG or CT, but not with antigen alone.
      Whereas vaccination with denatured OVA plus CpG markedly enhanced T helper 1
      (Th1) responses and inhibited IgE production, vaccination with denatured OVA plus
      CT increased cervical lymph node cell production of interleukin-4 (IL-4), IL-5,
      IL-6, and serum IgG1 responses. These data demonstrate that neonatal sublingual
      vaccination with denatured OVA and CpG not only preferentially induces systemic
      Th1 responses and mucosal immunity, but also simultaneously abrogates IgE
      production. Neonatal sublingual vaccines may play a role for the strategy of
      allergy prevention.

PMID- 18822110
TI  - CD8+CD60+ T cells, cells expressing epsilon specific mRNA and Th1/Th2 cytokines
      in cord blood and at 7 months of age.
AB  - IgE levels in cord blood have been investigated as predictors of atopy, but no
      definitive findings have been made. Other factors, including cells and/or
      cytokines may serve as predictors of this disease. Cord blood and peripheral
      blood was obtained at birth and at 7 months of age, respectively, from children
      (n = 2) with a family history of allergy. Cells in cord blood and peripheral
      blood were phenotyped and levels of serum immunoglobulins (IgM, IgG, IgA and IgE)
      were determined. In addition, placentas from these pregnancies were obtained and
      stained for IgE+ cells and CD8+CD60+ T cells. We found immunoglobulin levels were
      within normal ranges although IgE levels were negligible in cord blood and at 7
      months of age. Similar numbers of CD8+ T cells and CD19+ B cells were detected in
      cord blood and at 7 months of age. However, CD4+ T cells increased (twofold) and
      CD16+/CD56+ natural killer precursor cells decreased (twofold) at 7 months of
      age. CD8+ T cells in their cord blood and at 7 months of age comprised of >50%
      CD8+CD60+ T cells. Cord blood cells expressed epsilon-specific mRNA and mRNA for
      interleukin-2 (IL-2), IL-4, IL-10 and interferon-gamma (IFN-gamma) but not IL-6.
      At 7 months of age, peripheral blood mononuclear cells expressed epsilon-specific
      mRNA and mRNA for all cytokines. In the placental membrane, we detected IgE+
      cells, while CD8+CD60+ T cells were detected in the chorionic villi. CD8+CD60+ T
      cells, cells expressing epsilon-specific and IL-6-specific mRNA may contribute to
      the pathobiology and provide important prognostic indicators of atopy.

PMID- 18822111
TI  - Smoking status in relation to serum folate and dietary vitamin intake.
AB  - OBJECTIVE: Cigarette smoke itself is an abundant source of free radicals and a
      major cause of oxidative stress, to which plasma antioxidants function as a vital
      protective and counterbalancing mechanism. The objective of this study was to
      investigate into the relationship between smoking status and serum and dietary
      micronutrient concentrations. DESIGN: Cross-sectional study SUBJECTS - SETTING:
      502 farmers from the Valley of Messara in Crete were randomly selected and
      examined. Complete three-day and 24-hr recall questionnaires were collected along
      with anthropometrical, physical activity and clinical data from all participating
      subjects. RESULTS: After adjusting for age, gender and number of fasting days
      adhered to per year, current smokers were found to have a lower dietary intake of
      vitamin C (112.1 mg vs. 136.4 mg, p = 0.03), fibre (16.6 g vs. 19.1 g, p = 0.006)
      and fruits and vegetables (339 g vs. 412 g, p = 0.014), while dietary vitamin B1
      intake was found to be higher (1.7 mg vs. 1.4 mg, p = 0.02) in comparison to
      non/ex smokers. Dietary intake of meat, folate and vitami A, E, B2, B6 and B12
      did not differ between the groups. Controlling age, gender, fasting days and
      dietary micronutrient intake, serum folate levels were found to be lower among
      smokers (geometric mean 15.3 nmol/L vs. 17.7 nmol/L, p = 0.023), while serum iron
      and vitamin B12 levels were not affected by smoking status. CONCLUSION: Current
      smoking status affects dietary nutrient intake as well as plasma folate levels.
      The above coherence between antioxidant depletion and reduced antioxidant intake
      may predispose smokers to the premature development of tobacco related mortality
      and morbidity.

PMID- 18822112
TI  - A review of estimation of distribution algorithms in bioinformatics.
AB  - Evolutionary search algorithms have become an essential asset in the algorithmic
      toolbox for solving high-dimensional optimization problems in across a broad
      range of bioinformatics problems. Genetic algorithms, the most well-known and
      representative evolutionary search technique, have been the subject of the major
      part of such applications. Estimation of distribution algorithms (EDAs) offer a
      novel evolutionary paradigm that constitutes a natural and attractive alternative
      to genetic algorithms. They make use of a probabilistic model, learnt from the
      promising solutions, to guide the search process. In this paper, we set out a
      basic taxonomy of EDA techniques, underlining the nature and complexity of the
      probabilistic model of each EDA variant. We review a set of innovative works that
      make use of EDA techniques to solve challenging bioinformatics problems,
      emphasizing the EDA paradigm's potential for further research in this domain.

PMID- 18822113
TI  - Search extension transforms Wiki into a relational system: a case for flavonoid
      metabolite database.
AB  - BACKGROUND: In computer science, database systems are based on the relational
      model founded by Edgar Codd in 1970. On the other hand, in the area of biology
      the word 'database' often refers to loosely formatted, very large text files.
      Although such bio-databases may describe conflicts or ambiguities (e.g. a protein
      pair do and do not interact, or unknown parameters) in a positive sense, the
      flexibility of the data format sacrifices a systematic query mechanism equivalent
      to the widely used SQL. RESULTS: To overcome this disadvantage, we propose
      embeddable string-search commands on a Wiki-based system and designed a half
      formatted database. As proof of principle, a database of flavonoid with 6902
      molecular structures from over 1687 plant species was implemented on MediaWiki,
      the background system of Wikipedia. Registered users can describe any information
      in an arbitrary format. Structured part is subject to text-string searches to
      realize relational operations. The system was written in PHP language as the
      extension of MediaWiki. All modifications are open-source and publicly available.
      CONCLUSION: This scheme benefits from both the free-formatted Wiki style and the
      concise and structured relational-database style. MediaWiki supports multi-user
      environments for document management, and the cost for database maintenance is
      alleviated.

PMID- 18822114
TI  - Mining tissue specificity, gene connectivity and disease association to reveal a
      set of genes that modify the action of disease causing genes.
AB  - BACKGROUND: The tissue specificity of gene expression has been linked to a number
      of significant outcomes including level of expression, and differential rates of
      polymorphism, evolution and disease association. Recent studies have also shown
      the importance of exploring differential gene connectivity and sequence
      conservation in the identification of disease-associated genes. However, no study
      relates gene interactions with tissue specificity and disease association.
      METHODS: We adopted an a priori approach making as few assumptions as possible to
      analyse the interplay among gene-gene interactions with tissue specificity and
      its subsequent likelihood of association with disease. We mined three large
      datasets comprising expression data drawn from massively parallel signature
      sequencing across 32 tissues, describing a set of 55,606 true positive
      interactions for 7,197 genes, and microarray expression results generated during
      the profiling of systemic inflammation, from which 126,543 interactions among
      7,090 genes were reported. RESULTS: Amongst the myriad of complex relationships
      identified between expression, disease, connectivity and tissue specificity, some
      interesting patterns emerged. These include elevated rates of expression and
      network connectivity in housekeeping and disease-associated tissue-specific
      genes. We found that disease-associated genes are more likely to show tissue
      specific expression and most frequently interact with other disease genes. Using
      the thresholds defined in these observations, we develop a guilt-by-association
      algorithm and discover a group of 112 non-disease annotated genes that
      predominantly interact with disease-associated genes, impacting on disease
      outcomes. CONCLUSION: We conclude that parameters such as tissue specificity and
      network connectivity can be used in combination to identify a group of genes, not
      previously confirmed as disease causing, that are involved in interactions with
      disease causing genes. Our guilt-by-association algorithm should be useful for
      the discovery of additional modifiers of genetic diseases, and more generally,
      for the ability to associate genes of unknown function to clusters of genes with
      defined functions allowing for novel biological inference that can be
      subsequently validated.

PMID- 18822115
TI  - Fast approximate hierarchical clustering using similarity heuristics.
AB  - BACKGROUND: Agglomerative hierarchical clustering (AHC) is a common unsupervised
      data analysis technique used in several biological applications. Standard AHC
      methods require that all pairwise distances between data objects must be known.
      With ever-increasing data sizes this quadratic complexity poses problems that
      cannot be overcome by simply waiting for faster computers. RESULTS: We propose an
      approximate AHC algorithm HappieClust which can output a biologically meaningful
      clustering of a large dataset more than an order of magnitude faster than full
      AHC algorithms. The key to the algorithm is to limit the number of calculated
      pairwise distances to a carefully chosen subset of all possible distances. We
      choose distances using a similarity heuristic based on a small set of pivot
      objects. The heuristic efficiently finds pairs of similar objects and these help
      to mimic the greedy choices of full AHC. Quality of approximate AHC as compared
      to full AHC is studied with three measures. The first measure evaluates the
      global quality of the achieved clustering, while the second compares biological
      relevance using enrichment of biological functions in every subtree of the
      clusterings. The third measure studies how well the contents of subtrees are
      conserved between the clusterings. CONCLUSION: The HappieClust algorithm is well
      suited for large-scale gene expression visualization and analysis both on
      personal computers as well as public online web applications. The software is
      available from the URL http://www.quretec.com/HappieClust.

PMID- 18822116
TI  - Ultrasound evaluation of the abductor hallucis muscle: Reliability study.
AB  - BACKGROUND: The Abductor hallucis muscle (AbdH) plays an integral role during
      gait and is often affected in pathological foot conditions. The aim of this study
      was to evaluate the within and between-session intra-tester reliability using
      diagnostic ultrasound of the dorso-plantar thickness, medio-lateral width and
      cross-sectional area, of the AbdH in asymptomatic adults. METHODS: The AbdH
      muscles of thirty asymptomatic subjects were imaged and then measured using a
      Philips HD11 Ultrasound machine. Interclass correlation coefficients (ICC) with
      95% confidence intervals (CI) were used to calculate both within and between
      session intra-tester reliability. RESULTS: The within-session reliability results
      demonstrated for dorso-plantar thickness an ICC of 0.97 (95% CI: 0.99-0.99);
      medio-lateral width an ICC: of 0.97 (95% CI: 0.92-0.97) and cross-sectional area
      an ICC of 0.98 (95% CI: 0.98-0.99). Between-session reliability results
      demonstrated for dorso-plantar thickness an ICC of 0.97 (95% CI: 0.95 to 0.98);
      medio-lateral width an ICC of 0.94 (95% CI 0.90 to 0.96) and for cross-sectional
      area an ICC of 0.79 (95% CI 0.65 to 0.88). CONCLUSION: Diagnostic ultrasound has
      the potential to be a reliable tool for evaluating the AbdH muscle in
      asymptomatic subjects. Subsequent studies may be conducted to provide a better
      understanding of the AbdH function in foot and ankle pathologies.

PMID- 18822117
TI  - Chromosomal evolution of the PKD1 gene family in primates.
AB  - BACKGROUND: The autosomal dominant polycystic kidney disease (ADPKD) is mostly
      caused by mutations in the PKD1 (polycystic kidney disease 1) gene located in
      16p13.3. Moreover, there are six pseudogenes of PKD1 that are located proximal to
      the master gene in 16p13.1. In contrast, no pseudogene could be detected in the
      mouse genome, only a single copy gene on chromosome 17. The question arises how
      the human situation originated phylogenetically. To address this question we
      applied comparative FISH-mapping of a human PKD1-containing genomic BAC clone and
      a PKD1-cDNA clone to chromosomes of a variety of primate species and the dog as a
      non-primate outgroup species. RESULTS: Comparative FISH with the PKD1-cDNA clone
      clearly shows that in all primate species studied distinct single signals map in
      subtelomeric chromosomal positions orthologous to the short arm of human
      chromosome 16 harbouring the master PKD1 gene. Only in human and African great
      apes, but not in orangutan, FISH with both BAC and cDNA clones reveals additional
      signal clusters located proximal of and clearly separated from the PKD1 master
      genes indicating the chromosomal position of PKD1 pseudogenes in 16p of these
      species, respectively. Indeed, this is in accordance with sequencing data in
      human, chimpanzee and orangutan. Apart from the master PKD1 gene, six pseudogenes
      are identified in both, human and chimpanzee, while only a single-copy gene is
      present in the whole-genome sequence of orangutan. The phylogenetic
      reconstruction of the PKD1-tree reveals that all human pseudogenes are closely
      related to the human PKD1 gene, and all chimpanzee pseudogenes are closely
      related to the chimpanzee PKD1 gene. However, our statistical analyses provide
      strong indication that gene conversion events may have occurred within the PKD1
      family members of human and chimpanzee, respectively. CONCLUSION: PKD1 must have
      undergone amplification very recently in hominid evolution. Duplicative
      transposition of the PKD1 gene and further amplification and evolution of the
      PKD1 pseudogenes may have arisen in a common ancestor of Homo, Pan and Gorilla
      approximately 8 MYA. Reticulate evolutionary processes such as gene conversion
      and non-allelic homologous recombination (NAHR) may have resulted in concerted
      evolution of PKD1 family members in human and chimpanzee and, thus, simulate an
      independent evolution of the PKD1 pseudogenes from their master PKD1 genes in
      human and chimpanzee.

PMID- 18822118
TI  - The methodological quality of systematic reviews comparing temporomandibular
      joint disorder surgical and non-surgical treatment.
AB  - BACKGROUND: Temporomandibular joint disorders (TMJD) are multifactor, complex
      clinical problems affecting approximately 60-70% of the general population, with
      considerable controversy about the most effective treatment. For example, reports
      claim success rates of 70% and 83% for non-surgical and surgical treatment,
      whereas other reports claim success rates of 40% to 70% for self-improvement
      without treatment. Therefore, the purpose of this study was to (1) identify
      systematic reviews comparing temporomandibular joint disorder surgical and non
      surgical treatment, (2) evaluate their methodological quality, and (3) evaluate
      the evidence grade within the systematic reviews. METHODS: A search strategy was
      developed and implemented for MEDLINE, Cochrane Library, LILACS, and Brazilian
      Dentistry Bibliography databases. Inclusion criteria were: systematic reviews (+/
      meta-analysis) comparing surgical and non-surgical TMJD treatment, published in
      English, Spanish, Portuguese, Italian, or German between the years 1966 and
      2007(up to July). Exclusion criteria were: in vitro or animal studies; narrative
      reviews or editorials or editorial letters; and articles published in other
      languages. Two investigators independently selected and evaluated systematic
      reviews. Three different instruments (AMSTAR, OQAQ and CASP) were used to
      evaluate methodological quality, and the results averaged. The GRADE instrument
      was used to evaluate the evidence grade within the reviews. RESULTS: The search
      strategy identified 211 reports; of which 2 were systematic reviews meeting
      inclusion criteria. The first review met 23.5 +/- 6.0% and the second met 77.5 +/
      12.8% of the methodological quality criteria (mean +/- sd). In these systematic
      reviews between 9 and 15% of the trials were graded as high quality, and 2 and 8%
      of the total number of patients were involved in these studies. CONCLUSION: The
      results indicate that in spite of the widespread impact of TMJD, and the
      multitude of potential interventions, clinicians have expended sparse attention
      to systematically implementing clinical trial methodology that would improve
      validity and reliability of outcome measures. With some 20 years of knowledge of
      evidence-based healthcare, the meager attention to these issues begins to raise
      ethical issues about TMJD trial conduct and clinical care.

PMID- 18822119
TI  - Transperitoneal laparoscopic adrenalectomy for metachronous contralateral adrenal
      metastasis from renal cell carcinoma: a case report.
AB  - BACKGROUND: We report a case of metachronous solitary metastasis of renal cell
      carcinoma to the contralateral adrenal gland treated by laparoscopic
      transperitoneal adrenalectomy. CASE PRESENTATION: A 58-year-old man presented to
      our institution for regular follow up, 2 years after a right radical nephrectomy
      with preservation of the ipsilateral adrenal gland, for a primary renal cell
      carcinoma. The patient remained asymptomatic but an abdominal computed tomography
      scan on follow up revealed a 6.5 x 4 cm2 mass in the left adrenal gland. A
      positron emission tomography scan was also performed to rule out other possible
      metastases, and a magnetic resonance imaging scan was used for accurate
      localization and determination of resectability of the adrenal tumour. A bone
      scan, metabolic screen, liver and renal function tests were all within normal
      limits. A laparoscopic transperitoneal adrenalectomy was then performed. The
      postoperative period was uneventful, and the patient was discharged on
      postoperative day two. The patient remains in satisfactory condition and no
      recurrence or adrenal insufficiency has been observed during 12 months follow up.
      CONCLUSION: Metachronous contra lateral adrenal metastases from primary renal
      cell carcinoma are very rare but should always be suspected in any nephrectomised
      patient presenting with an adrenal tumour. Regular follow up in these patients
      accompanied with computed tomography imaging may help the surgeon to detect early
      lesions. Laparoscopic transperitoneal adrenalectomy is feasible, safe and
      effective, with minimal trauma to the patient.

PMID- 18822120
TI  - Menopause, postmenopausal hormone use and serum uric acid levels in US women--the
      Third National Health and Nutrition Examination Survey.
AB  - INTRODUCTION: Despite the substantial prevalence of gout in the ageing female
      population, female hormonal influence has not been comprehensively examined. We
      evaluated and quantified the potential independent association between menopause,
      postmenopausal hormone use and serum uric acid levels in a nationally
      representative sample of women. METHODS: Using data from 7662 women aged 20 years
      and older in the Third National Health and Nutrition Examination Survey (1988 to
      1994), we examined the relation between menopause, postmenopausal hormone use and
      serum uric acid levels. We used multivariate linear regression to adjust for
      other risk factors for hyperuricaemia such as dietary factors, age, adiposity,
      alcohol use, renal function, hypertension and diuretic use. RESULTS: Menopause
      was associated with higher serum uric acid levels. After adjusting for
      covariates, serum uric acid levels among women with natural menopause and
      surgical menopause were greater than premenopausal women by 0.34 mg/dl (95%
      confidence interval [CI], 0.19 to 0.49) and 0.36 mg/dl (95% CI, 0.14 to 0.57),
      respectively. Current postmenopausal hormone use was associated with a lower
      serum uric acid level among postmenopausal women (multivariate difference, 0.24
      mg/dl [95% CI, 0.11 to 0.36]). The serum uric acid levels increased with
      increasing age categories (crude difference between 20 to 29 years and 70 years
      and over = 1.03 mg/dl, p for trend < 0.001), but this increase was not present
      after adjusting for other covariates (p for trend = 0.66). CONCLUSIONS: These
      findings from a nationally representative sample of US women indicate that
      menopause is independently associated with higher serum uric acid levels, whereas
      postmenopausal hormone use is associated with lower uric acid levels among
      postmenopausal women. The age-associated increase in serum uric acid levels in
      women may be explained by menopause and other age-related factors.

PMID- 18822121
TI  - Pioglitazone retrieves hepatic antioxidant DNA repair in a mice model of high fat
      diet.
AB  - BACKGROUND: Pioglitazone was reported to improve hepatic steatosis and
      necroinflammation in human studies. To investigate whether the hepato-protective
      effect of pioglitazone was associated with an improvement of antioxidant defense
      mechanism, oxidative DNA damage and repair activity were determined in a high fat
      diet model. Male C57BL/6 mice were respectively fed with a 30% fat diet, the same
      diet with pioglitazone 100 mg/kg/day, or a chow diet as control for 8 weeks.
      Tissue oxidative stress was indicated by malondialdehyde concentration. Oxidative
      DNA damage was detected by immunohistochemical 8-oxoG staining. Enzymatic
      antioxidant defense was detected by the real-time PCR of superoxide dismutase
      (Sod1, Sod2) and DNA glycosylase (Ogg1, MutY). Oxidative DNA repair was detected
      by immunohistochemical staining and western blotting of OGG1 expression. RESULTS:
      Our results show that hepatic steatosis was induced by a high-fat diet and
      improved by adding pioglitazone. Malondialdehyde concentration and 8-oxoG
      staining were strongly increased in the high-fat diet group, but attenuated by
      pioglitazone. Gene expressions of antioxidant defense mechanism: Sod1, Sod2, Ogg1
      and MutY significantly decreased in the high-fat diet group but reversed by
      pioglitazone co-administration. CONCLUSION: The attenuation of hepatic oxidative
      DNA damage by pioglitazone in a high-fat diet may be mediated by up-regulation of
      the antioxidant defense mechanism and oxidative DNA repair activity. The
      diminution of oxidative damage may explain the clinical benefit of pioglitazone
      treatment in patients with non-alcoholic fatty liver disease.

PMID- 18822122
TI  - Variation in incidence of breast, lung and cervical cancer and malignant melanoma
      of skin by socioeconomic group in England.
AB  - BACKGROUND: Cancer incidence varies by socioeconomic group and these variations
      have been linked with environmental and lifestyle factors, differences in access
      to health care and health seeking behaviour. Socioeconomic variations in cancer
      incidence by region and age are less clearly understood but they are crucial for
      targeting prevention measures and health care commissioning. METHODS: Data were
      obtained from all eight English cancer registries for patients diagnosed between
      1998 and 2003, for all invasive cases of female breast cancer (ICD-10 code C50),
      lung cancer (ICD-10 codes C33-C34), cervical cancer (ICD-10 code C53), and
      malignant melanoma of the skin (ICD-10 code C43). Socioeconomic status was
      assigned to each patient based on their postcode of residence at diagnosis, using
      the income domain of the Index of Multiple Deprivation 2004. We analysed the
      socioeconomic variations in the incidence of breast, lung and cervical cancer and
      malignant melanoma of the skin for England, and regionally and by age. RESULTS:
      Incidence was highest for the most deprived patients for lung cancer and cervical
      cancer, whilst the opposite was observed for malignant melanoma and breast
      cancer. The difference in incidence between the most and the least deprived
      groups was higher for lung cancer patients aged under 65 at diagnosis than those
      over 65 at diagnosis, which may indicate a cohort effect. There were regional
      differences in the socioeconomic gradients with the gap being widest for lung and
      cervical cancer in the North (North East, North West and Yorkshire and
      Humberside) and for malignant melanoma in the East and South West. There were
      only modest variations in breast cancer incidence by region. If the incidence of
      lung and cervical cancer were decreased to that of the least deprived group it
      would prevent 36% of lung cancer cases in men, 38% of lung cancer cases in women
      and 28% of cervical cancer cases. Incidence of breast cancer and melanoma was
      highest in the least deprived group, therefore if all socioeconomic groups had
      incidence rates similar to the least deprived group it is estimated that the
      number of cases would increase by 7% for breast cancer, 27% for melanoma in men
      and 29% for melanoma in women. CONCLUSION: National comparison of socioeconomic
      variations in cancer incidence by region and age can provide an unbiased basis
      for public health prevention and health commissioning. Decreasing inequalities in
      incidence requires the integration of information on risk factors, incidence and
      projected incidence but targeted public health interventions could help to reduce
      regional inequalities in incidence and reduce the future cancer burden.

PMID- 18822123
TI  - Early intestinal Bacteroides fragilis colonisation and development of asthma.
AB  - BACKGROUND: The 'hygiene hypothesis' suggests that early exposure to microbes can
      be protective against atopic disease. The intestinal microbial flora could
      operate as an important postnatal regulator of the Th1/Th2 balance. The aim of
      the study was to investigate the association between early intestinal
      colonisation and the development of asthma in the first 3 years of life. METHODS:
      In a prospective birth cohort, 117 children were classified according to the
      Asthma Predictive Index. A positive index included wheezing during the first
      three years of life combined with eczema in the child in the first years of life
      or with a parental history of asthma. A faecal sample was taken at the age of 3
      weeks and cultured on selective media. RESULTS: Asthma Predictive Index was
      positive in 26/117 (22%) of the children. The prevalence of colonisation with
      Bacteroides fragilis was higher at 3 weeks in index+ compared to index- children
      (64% vs. 34% p < 0,05). Bacteroides fragilis and Total Anaerobes counts at 3
      weeks were significantly higher in children with a positive index as compared
      with those without. After adjusting for confounders a positive association was
      found between Bacteroides fragilis colonisation and Asthma Predictive Index (odds
      ratio: 4,4; confidence interval: 1,7 - 11,8). CONCLUSION: Bacteroides fragilis
      colonisation at age 3 weeks is an early indicator of possible asthma later in
      life. This study could provide the means for more accurate targeting of treatment
      and prevention and thus more effective and better controlled modulation of the
      microbial milieu.

PMID- 18822124
TI  - Exhaled and arterial levels of endothelin-1 are increased and correlate with
      pulmonary systolic pressure in COPD with pulmonary hypertension.
AB  - BACKGROUND: Endothelin-1 (ET-1) and Nitric Oxide (NO) are crucial mediators for
      establishing pulmonary artery hypertension (PAH). We tested the hypothesis that
      their imbalance might also occur in COPD patients with PAH. METHODS: The aims of
      the study were to measure exhaled breath condensate (EBC) and circulating levels
      of ET-1, as well as exhaled NO (FENO) levels by, respectively, a specific enzyme
      immunoassay kit, and by chemiluminescence analysis in 3 groups of subjects: COPD
      with PAH (12), COPD only (36), and healthy individuals (15). In order to evaluate
      pulmonary-artery systolic pressure (PaPs), all COPD patients underwent Echo
      Doppler assessment. RESULTS: Significantly increased exhaled and circulating
      levels of ET-1 were found in COPD with PAH compared to both COPD (p < 0.0001)
      only, and healthy controls (p < 0.0001). In COPD with PAH, linear regression
      analysis showed good correlation between ET-1 in EBC and PaPs (r = 0.621; p =
      0.031), and between arterial levels of ET-1 and PaPs (r = 0.648; p = 0.022),
      while arterial levels of ET-1 inversely correlated with FEV1%, (r = -0.59, p =
      0.043), and PaPs negatively correlated to PaO2 (r = -0.618; p = 0.032).
      Significantly reduced levels of FENO were found in COPD associated with PAH,
      compared to COPD only (22.92 +/- 11.38 vs.35.07 +/- 17.53 ppb; p = 0.03). Thus,
      we observed an imbalanced output in the breath between ET-1 and NO, as expression
      of pulmonary endothelium and epithelium impairment, in COPD with PAH compared to
      COPD only. Whether this imbalance is an early cause or result of PAH due to COPD
      is still unknown and deserves further investigations.

PMID- 18822125
TI  - High-throughput Agrobacterium-mediated barley transformation.
AB  - BACKGROUND: Plant transformation is an invaluable tool for basic plant research,
      as well as a useful technique for the direct improvement of commercial crops.
      Barley (Hordeum vulgare) is the fourth most abundant cereal crop in the world. It
      also provides a useful model for the study of wheat, which has a larger and more
      complex genome. Most existing barley transformation methodologies are either
      complex or have low (<10%) transformation efficiencies. RESULTS: A robust, simple
      and reproducible barley transformation protocol has been developed that yields
      average transformation efficiencies of 25%. This protocol is based on the
      infection of immature barley embryos with Agrobacterium strain AGL1, carrying
      vectors from the pBract series that contain the hpt gene (conferring hygromycin
      resistance) as a selectable marker. Results of large scale experiments utilising
      the luc (firefly luciferase) gene as a reporter are described. The method
      presented here has been used to produce hundreds of independent, transgenic plant
      lines and we show that a large proportion of these lines contain single copies of
      the luc gene. CONCLUSION: This protocol demonstrates significant improvements in
      both efficiency and ease of use over existing barley transformation methods. This
      opens up opportunities for the development of functional genomics resources in
      barley.

PMID- 18822126
TI  - Discovery of frameshifting in Alphavirus 6K resolves a 20-year enigma.
AB  - BACKGROUND: The genus Alphavirus includes several potentially lethal human
      viruses. Additionally, species such as Sindbis virus and Semliki Forest virus are
      important vectors for gene therapy, vaccination and cancer research, and
      important models for virion assembly and structural analyses. The genome encodes
      nine known proteins, including the small '6K' protein. 6K appears to be involved
      in envelope protein processing, membrane permeabilization, virion assembly and
      virus budding. In protein gels, 6K migrates as a doublet--a result that, to date,
      has been attributed to differing degrees of acylation. Nonetheless, despite many
      years of research, its role is still relatively poorly understood. RESULTS: We
      report that ribosomal -1 frameshifting, with an estimated efficiency of
      approximately 10-18%, occurs at a conserved UUUUUUA motif within the sequence
      encoding 6K, resulting in the synthesis of an additional protein, termed TF
      (TransFrame protein; approximately 8 kDa), in which the C-terminal amino acids
      are encoded by the -1 frame. The presence of TF in the Semliki Forest virion was
      confirmed by mass spectrometry. The expression patterns of TF and 6K were studied
      by pulse-chase labelling, immunoprecipitation and immunofluorescence, using both
      wild-type virus and a TF knockout mutant. We show that it is predominantly TF
      that is incorporated into the virion, not 6K as previously believed.
      Investigation of the 3' stimulatory signals responsible for efficient
      frameshifting at the UUUUUUA motif revealed a remarkable diversity of signals
      between different alphavirus species. CONCLUSION: Our results provide a
      surprising new explanation for the 6K doublet, demand a fundamental
      reinterpretation of existing data on the alphavirus 6K protein, and open the way
      for future progress in the further characterization of the 6K and TF proteins.
      The results have implications for alphavirus biology, virion structure,
      viroporins, ribosomal frameshifting, and bioinformatic identification of novel
      frameshift-expressed genes, both in viruses and in cellular organisms.

PMID- 18822127
TI  - Wnt and Frizzled RNA expression in human mesenchymal and embryonic (H7) stem
      cells.
AB  - BACKGROUND: Wnt signals are important for embryonic stem cells renewal, growth
      and differentiation. Although 19 Wnt, 10 Frizzled genes have been identified in
      mammals, their expression patterns in stem cells were largely unknown. RESULTS:
      We conducted RNA expression profiling for the Wnt ligands, their cellular
      receptors "Frizzleds" and co-receptors LRP5/6 in human embryonic stem cells (H7),
      human bone marrow mesenchymal cells, as well as mouse totipotent F9
      teratocarcinoma embryonal cells. Except failing to express Wnt2 gene, totipotent
      F9 cells expressed RNA for all other 18 Wnt genes as well as all 10 members of
      Frizzled gene family. H7 cells expressed RNA for each of the 19 Wnt genes. In
      contrast, human mesenchymal cells did not display detectable RNA expression of
      Wnt1, Wnt8a, Wnt8b, Wnt9b, Wnt10a, and Wnt11. Analysis of Frizzled RNAs in H7 and
      human mesechymal cells revealed expression of 9 members of the receptor gene
      family, except Frizzled8. Expression of the Frizzled co-receptor LRP5 and LRP6
      genes were detected in all three cell lines. Human H7 and mouse F9 cells express
      nearly a full complement of both Wnts and Frizzleds genes. The human mesenchymal
      cells, in contrast, have lost the expression of six Wnt ligands, i.e. Wnt1, 8a,
      8b, 9b, 10a and 11. CONCLUSION: Puripotent human H7 and mouse F9 embryonal cells
      express the genes for most of the Wnts and Frizzleds. In contrast, multipotent
      human mesenchymal cells are deficient in expression of Frizzled-8 and of 6 Wnt
      genes.

PMID- 18822128
TI  - The Cues and Care Trial: a randomized controlled trial of an intervention to
      reduce maternal anxiety and improve developmental outcomes in very low
      birthweight infants.
AB  - BACKGROUND: Very low birthweight infants are at risk for deficits in cognitive
      and language development, as well as attention and behaviour problems. Maternal
      sensitive behaviour (i.e. awareness of infant cues and appropriate responsiveness
      to those cues) in interaction with her very low birthweight infant is associated
      with better outcomes in these domains; however, maternal anxiety interferes with
      the mother's ability to interact sensitively with her very low birthweight
      infant. There is a need for brief, cost-effective and timely interventions that
      address both maternal psychological distress and interactive behaviour. The Cues
      and Care trial is a randomized controlled trial of an intervention designed to
      reduce maternal anxiety and promote sensitive interaction in mothers of very low
      birthweight infants. METHODS AND DESIGN: Mothers of singleton infants born at
      weights below 1500 g are recruited in the neonatal intensive care units of 2
      tertiary care hospitals, and are randomly assigned to the experimental (Cues)
      intervention or to an attention control (Care) condition. The Cues intervention
      teaches mothers to attend to their own physiological, cognitive, and emotional
      cues that signal anxiety and worry, and to use cognitive-behavioural strategies
      to reduce distress. Mothers are also taught to understand infant cues and to
      respond sensitively to those cues. Mothers in the Care group receive general
      information about infant care. Both groups have 6 contacts with a trained
      intervener; 5 of the 6 sessions take place during the infant's hospitalization,
      and the sixth contact occurs after discharge, in the participant mother's home.
      The primary outcome is maternal symptoms of anxiety, assessed via self-report
      questionnaire immediately post-intervention. Secondary outcomes include maternal
      sensitive behaviour, maternal symptoms of posttraumatic stress, and infant
      development at 6 months corrected age. DISCUSSION: The Cues and Care trial will
      provide important information on the efficacy of a brief, skills-based
      intervention to reduce anxiety and increase sensitivity in mothers of very low
      birthweight infants. A brief intervention of this nature may be more readily
      implemented as part of standard neonatal intensive care than broad-based, multi
      component interventions. By intervening early, we aim to optimize developmental
      outcomes in these high risk infants. TRIAL REGISTRATION: Current Controlled
      Trials ISRCTN00918472. The Cues and Care Trial: A randomized controlled trial of
      an intervention to reduce maternal anxiety and improve developmental outcomes in
      very low birthweight infants.

PMID- 18822129
TI  - Regulatory subunits of PKA define an axis of cellular
      proliferation/differentiation in ovarian cancer cells.
AB  - BACKGROUND: The regulatory subunit of cAMP-dependent protein kinase (PKA) exists
      in two isoforms, RI and RII, which distinguish the PKA isozymes, type I (PKA-I)
      and type II (PKA-II). Evidence obtained from a variety of different experimental
      approaches has shown that the relative levels of type I and type II PKA in cells
      can play a major role in determining the balance between cell growth and
      differentiation. In order to characterize the effect of PKA type I and type II
      regulatory subunits on gene transcription at a global level, the PKA regulatory
      subunit genes for RIalpha and RIIbeta were stably transfected into cells of the
      ovarian cancer cell line (OVCAR8). RESULTS: RIalpha transfected cells exhibit
      hyper-proliferative growth and RIIbeta transfected cells revert to a relatively
      quiescent state. Profiling by microarray revealed equally profound changes in
      gene expression between RIalpha, RIIbeta, and parental OVCAR cells. Genes
      specifically up-regulated in RIalpha cells were highly enriched for pathways
      involved in cell growth while genes up-regulated in RIIbeta cells were enriched
      for pathways involved in differentiation. A large group of genes (~3600) was
      regulated along an axis of proliferation/differentiation between RIalpha,
      parental, and RIIbeta cells. RIalpha/wt and RIIbeta/wt gene regulation was shown
      by two separate and distinct gene set analytical methods to be strongly cross
      correlated with a generic model of cellular differentiation. CONCLUSION:
      Overexpression of PKA regulatory subunits in an ovarian cancer cell line
      dramatically influences the cell phenotype. The proliferation phenotype is
      strongly correlated with recently identified clinical biomarkers predictive of
      poor prognosis in ovarian cancer suggesting a possible pivotal role for PKA
      regulation in disease progression.

PMID- 18822130
TI  - Correlates of susceptibility to smoking among Mexican origin youth residing in
      Houston, Texas: a cross-sectional analysis.
AB  - BACKGROUND: Survey data suggest that in Texas Latino youth exhibit higher rates
      of susceptibility to smoking than youth from other ethnic groups. In this
      analysis we examined the relationship between susceptibility to smoking and well
      known risk factors associated with smoking initiation among a cohort of 11 to 13
      year old Mexican origin youth residing in Houston, Texas. METHODS: We analyzed
      cross-sectional survey data from 1,187 participants who reported they had never
      smoked, even a puff of a cigarette. The survey assessed peer and family social
      influence, school and neighborhood characteristics, level of family acculturation
      and socioeconomic status, and attitudes toward smoking. Bivariate associations,
      Student's t-tests, and logistic regression analysis were used to examine
      predictors of susceptibility. RESULTS: Overall, 22.1% of the never-smokers were
      susceptible to smoking. Boys were more likely to be susceptible than girls (25.6%
      vs. 18.9%), and susceptible children were slightly older than non-susceptible
      children (12.1 vs. 11.8 years). In addition, multivariate analyses revealed that
      positive expectations about smoking exerted the strongest influence on
      susceptibility status (odds ratio = 4.85). Multivariate analyses further revealed
      that compared to non-susceptible participants, susceptibles were more likely to
      report peer influences supportive of smoking, lower subjective social status and
      more detentions at school, more temptations to try smoking and to have a mother
      and a brother who smokes. CONCLUSION: Our findings suggest that interventions
      that target positive expectations about smoking may be useful in this population.
      Furthermore, because youth encounter smoking-initiation risk factors in different
      social environments, our results underscore the continued need for both family-
      and school-based primary prevention programs to adequately combat their
      influence. The results also can be used to inform the development of culturally
      sensitive programs for Mexican origin youth.

PMID- 18822131
TI  - RASSF1A protein expression and correlation with clinicopathological parameters in
      renal cell carcinoma.
AB  - BACKGROUND: Epigenetic silencing of RAS association family 1A (RASSF1A) tumor
      suppressor gene occurs in various histological subtypes of renal cell carcinoma
      (RCC) but RASSF1A protein expression in clear cell RCC as well as a possible
      correlation with clinicopathological parameters of patients has not been analyzed
      at yet. METHODS: 318 primary clear cell carcinomas were analyzed using tissue
      microarray analysis and immunohistochemistry. Survival analysis was carried out
      for 187 patients considering a follow-up period of 2-240 month. RESULTS:
      Expression of RASSF1A was found to be significantly decreased in tumoral cells
      when compared to normal tubular epithelial cells. RASSF1A immunopositivity was
      significantly associated with pT stage, group stage and histological grade of
      tumors and showed a tendency for impaired survival in Kaplan-Meier analysis.
      CONCLUSION: While most tumors demonstrate a loss of RASSF1A protein, a subset of
      tumors was identified to exhibit substantial RASSF1A protein expression and show
      increased tumor progression. Thus RCC tumorigenesis without depletion of RASSF1A
      may be associated with an adverse clinical outcome.

PMID- 18822132
TI  - Bioinformatic and statistical analysis of the optic nerve head in a primate model
      of ocular hypertension.
AB  - BACKGROUND: The nonhuman primate model of glaucomatous optic neuropathy most
      faithfully reproduces the human disease. We used high-density oligonucleotide
      arrays to investigate whole genome transcriptional changes occurring at the optic
      nerve head during primate experimental glaucoma. RESULTS: Laser scarification of
      the trabecular meshwork of cynomolgus macaques produced elevated intraocular
      pressure that was monitored over time and led to varying degrees of damage in
      different samples. The macaques were examined clinically before enucleation and
      the myelinated optic nerves were processed post-mortem to determine the degree of
      neuronal loss. Global gene expression was examined in dissected optic nerve heads
      with Affymetrix GeneChip microarrays. We validated a subset of differentially
      expressed genes using qRT-PCR, immunohistochemistry, and immuno-enriched
      astrocytes from healthy and glaucomatous human donors. These genes have
      previously defined roles in axonal outgrowth, immune response, cell motility,
      neuroprotection, and extracellular matrix remodeling. CONCLUSION: Our findings
      show that glaucoma is associated with increased expression of genes that mediate
      axonal outgrowth, immune response, cell motility, neuroprotection, and ECM
      remodeling. These studies also reveal that, as glaucoma progresses, retinal
      ganglion cell axons may make a regenerative attempt to restore lost nerve cell
      contact.

PMID- 18822133
TI  - A Dutch guideline for the treatment of scoliosis in neuromuscular disorders.
AB  - BACKGROUND: Children with neuromuscular disorders with a progressive muscle
      weakness such as Duchenne Muscular Dystrophy and Spinal Muscular Atrophy
      frequently develop a progressive scoliosis. A severe scoliosis compromises
      respiratory function and makes sitting more difficult. Spinal surgery is
      considered the primary treatment option for correcting severe scoliosis in
      neuromuscular disorders. Surgery in this population requires a multidisciplinary
      approach, careful planning, dedicated surgical procedures, and specialized after
      care. METHODS: The guideline is based on scientific evidence and expert opinions.
      A multidisciplinary working group representing experts from all relevant
      specialties performed the research. A literature search was conducted to collect
      scientific evidence in answer to specific questions posed by the working group.
      Literature was classified according to the level of evidence. RESULTS: For most
      aspects of the treatment scientific evidence is scarce and only low level cohort
      studies were found. Nevertheless, a high degree of consensus was reached about
      the management of patients with scoliosis in neuromuscular disorders. This was
      translated into a set of recommendations, which are now officially accepted as a
      general guideline in the Netherlands. CONCLUSION: In order to optimize the
      treatment for scoliosis in neuromuscular disorders a Dutch guideline has been
      composed. This evidence-based, multidisciplinary guideline addresses conservative
      treatment, the preoperative, perioperative, and postoperative care of scoliosis
      in neuromuscular disorders.

PMID- 18822134
TI  - Pathway to psychiatric care in Japan: A multicenter observational study.
AB  - BACKGROUND: This study examines pathways to psychiatric care in Japan using the
      same method as the collaborative study carried out in 1991 under the auspices of
      the World Health Organization. METHODS: Thirteen psychiatric facilities in Japan
      were involved. Of the 228 patients who contacted psychiatric facilities with any
      psychiatric illness, eighty four visiting psychiatric facilities for the first
      time were enrolled. Pathways to psychiatric care, delays from the onset of
      illness to treatment prior to reaching psychiatrists were surveyed. RESULTS:
      Thirty three patients (39.4%) directly accessed mental health professionals, 32
      patients (38.1%) reached them via general hospital, and 13 patients (15.5%) via
      private practitioners. The patients who consulted mental health professionals as
      their first carers took a longer time before consulting psychiatrists than the
      patients who consulted non-mental health professionals as their first carers. The
      patients who presented somatic symptoms as their main problem experienced longer
      delay from the onset of illness to psychiatric care than the patients who
      complained about depressive or anxiety symptoms. Prior to the visit to mental
      health professionals, patients were rarely informed about their diagnosis and did
      not receive appropriate treatments from their physicians. Private practitioners
      were more likely to prescribe psychotropics than physicians in general hospitals,
      but were less likely to inform their patients of their diagnosis. CONCLUSION:
      This first pathway to psychiatric care study in Japan demonstrated that referral
      pathway in Japan heavily relies on medical resources. The study indicates
      possible fields and gives indications, underlining the importance of improving
      skills and knowledge that will facilitate the recognition of psychiatric
      disorders presenting with somatic and depressive symptoms in the general health
      care system and by private practitioners.

PMID- 18822135
TI  - Investigation of Chlamydophila spp. in dairy cows with reproductive disorders.
AB  - BACKGROUND: Reports worldwide indicate high prevalence of Chlamydophila spp.
      infection in cattle. To assess the prevalence in Sweden, 525 cows in 70 dairy
      herds with reproductive disorders was investigated. METHODS: To detect antibodies
      two commercially available kits were used. Moreover, 107 specimens, including
      vaginal swabs, organ tissues and milk were analysed by Polymerase Chain Reaction
      (PCR). RESULTS: Two (0.4%) cows were seropositive in the Pourquier Cp. abortus
      ELISA. The seroprevalence with the Chekit ELISA was 28% with no difference
      between cases and controls. Five specimens were positive in real-time PCR and
      further analysed by nested PCR. Cp. pecorum was confirmed by partial omp1 DNA
      sequencing of the nested PCR product of vaginal swabs from control cows.
      CONCLUSION: The results suggest that Cp. abortus infection is absent or rare in
      Swedish cows whereas Cp. pecorum is probably more spread. They also suggest that
      Chlamydophila spp. are not related to reproduction disorders in Swedish cattle.

PMID- 18822136
TI  - Mutation detection analysis of a region of 16S-like ribosomal RNA gene of
      Entamoeba histolytica, Entamoeba dispar and Entamoeba moshkovskii.
AB  - BACKGROUND: The level of intra-species genetic variation in Entamoeba
      histolytica, Entamoeba dispar and Entamoeba moshkovskii populations in a
      localized geographic area, like Puducherry, India, remains unknown. METHODS: In
      the present study the existence of genetic variation in the nested multiplex
      polymerase chain reaction (NM-PCR) amplified region of the 16S-like ribosomal RNA
      genes of E. histolytica, E. dispar and E. moshkovskii was investigated by
      riboprinting and single strand conformation polymorphism (SSCP) analysis.
      RESULTS: We found that 70 stool specimens were positive for E. histolytica, 171
      stool specimens were positive for E. dispar, and 37 stool specimens were positive
      for E. moshkovskii by NM-PCR. Ninety liver abscess pus specimens, 21 urine
      specimens, and 8 saliva specimens were positive for E. histolytica by NM-PCR.
      Riboprinting analysis detected a mutation in the PCR product of only one E.
      histolytica isolate from a stool specimen. However, SSCP analysis detected
      mutations in the PCR products of five E. histolytica isolates and three E.
      moshkovskii isolates from stool specimens, and one E. histolytica isolate from a
      saliva specimen. The mutations detected by riboprinting and SSCP analysis were
      confirmed by sequencing. All the nucleotide sequences showing mutations in this
      study have already been deposited into the NCBI GenBank database under accession
      numbers [GenBank: EF682200 to GenBank: EF682208]. CONCLUSION: The present study
      has revealed the subsistence of mutations in the ribosomal RNA genes of E.
      histolytica and E. moshkovskii, which points towards the existence of intra
      species genetic variation in E. histolytica and E. moshkovskii isolates infecting
      humans.

PMID- 18822137
TI  - Role of Smac/DIABLO in cancer progression.
AB  - Second mitochondria-derived activator of caspase/direct inhibitor of apoptosis
      binding protein with low pI (Smac/DIABLO) is a proapoptogenic mitochondrial
      protein that is released to the cytosol in response to diverse apoptotic stimuli,
      including commonly used chemotherapeutic drugs. In the cytosol, Smac/DIABLO
      interacts and antagonizes inhibitors of apoptosis proteins (IAPs), thus allowing
      the activation of caspases and apoptosis. This activity has prompted the
      synthesis of peptidomimetics that could potentially be used in cancer therapy.
      For these reasons, several authors have analyzed the expression levels of
      Smac/DIABLO in samples of patients from different tumors. Although dissimilar
      results have been found, a tissue-specific role of this protein emerges from the
      data. The objective of this review is to present the current knowledge of the
      Smac/DIABLO role in cancer and its possible use as a marker or therapeutic target
      for drug design.

PMID- 18822138
TI  - The KBG syndrome: Case report.
AB  - INTRODUCTION: The KBG syndrome is a rare autosomal dominant condition, first
      described by Hermann et al. in 1975. Fundamental findings are: mild development
      delay, short stature, craniofacial dysmorphism and skeletal anomalies. CASE
      PRESENTATION: A 32 years old woman, Caucasian race, weight 57 Kg, affected by KBG
      syndrome was sent to our clinics for preoperative anaesthesia evaluation. She was
      schedules for left ossicular reconstruction under general anaesthesia for
      bilateral hearing loss. A psycho-motor retardation was associated to
      morphological anomalies such as short neck, hyperlordosis without neck extension
      imparirment, craniofacial anomalies and dento-skeletal abnormalities. An
      echocardiography showed the presence of interatrial defect with left-to-right
      shunt. The patient was sent to a cardiac surgery centre. CONCLUSION:
      Perioperative evaluation of patients affected by KBG syndrome must take into
      consideration the management of difficult airways, due to the associated
      craniofacial dysmorphism. The possible presence of cardiac anomalies in the KBG
      syndrome is currently being evalueted. In this report the finding of cardiomegaly
      and congestion of the pulmonary circulation was attributed to presence of an
      interatrial defect with left-to-right shunt. The risk of cardiopulmonary failure
      led us to ask for a cardiac surgery consult. Perioperative management of these
      patients should be extremely accurate, even in the case of minor surgery, and
      should include also chest X-rays and echocardiography evaluation.

PMID- 18822139
TI  - Investigating health effects in a community surrounding a road tunnel stack--a
      cross sectional study.
AB  - BACKGROUND: Extended tunnelled roadways requiring ventilation via exhaust stacks
      are an increasingly common solution to traffic congestion around the world. In
      response to community concerns about adverse health effects associated with
      emissions from a new road tunnel exhaust stack, despite no demonstrable change in
      local ambient air quality, we conducted a cross sectional study to test for an
      association between exposure to the exhaust stack emissions and the presence of
      eye, nose and throat symptoms. METHODS: Stack emissions were modelled and
      categorised into areas of high, medium and low levels of exposure to emissions. A
      telephone interview survey was conducted in these three zones. Multivariate
      analysis was undertaken using Cox Proportional Hazards modelling to estimate
      prevalence ratios between zones for eye, nose and throat symptoms. RESULTS: The
      prevalence of eye, nose and throat symptoms in the study area were 50 percent, 67
      percent and 33 percent respectively and did not differ between the exposure
      zones. The presence of these symptoms was associated with a measure of reported
      "environmental worry". CONCLUSION: The study did not demonstrate a community wide
      health impact associated with modelled emissions but is unable to exclude the
      possibility of sensitive individuals being adversely affected.

PMID- 18822140
TI  - Case reports: a helping hand to generalists.
AB  - Clinical decision making can be challenging for both generalists and specialists.
      Case reports may assist the decision making process either by providing guidance
      to generalists on identifying rarer conditions or a searchable database for
      looking up seemingly disparate symptoms. This editorial highlights the
      innovations being implemented by Journal of Medical Case Reports and Cases
      Journal in developing an educational resource to help clinicians in decision
      making.

PMID- 18822141
TI  - Kikuchi-Fujimoto Disease: A case report and review of the literature.
AB  - Kikuchi-Fujimoto Disease is a rare benign, condition of necrotising histiocytic
      lymphadenitis. A case of a 55 year old gentleman is described here. He presented
      with fevers, weight loss and tender cervical lymph nodes. Kikuchi-Fujimoto
      disease was diagnosed after cervical lymph node biopsy. Symptomatic treatment was
      provided and an uneventful full recovery was made. Of significant note, this
      patient's daughter had Kikuchi-Fujimoto disease almost a decade earlier. Although
      Kikuchi-Fujimoto disease has been reported widely, we believe this is the first
      familial report in the literature of a case of Kikuchi-Fujimoto disease occurring
      in a parent and child.

PMID- 18822142
TI  - The potential for measles transmission in England.
AB  - BACKGROUND: Since the schools vaccination campaign in 1994, measles has been
      eliminated from England. Maintaining elimination requires low susceptibility
      levels to keep the effective reproduction number R below 1. Since 1995, however,
      MMR coverage in two year old children has decreased by more than 10%. METHODS:
      Quarterly MMR coverage data for children aged two and five years resident in each
      district health authority in England were used to estimate susceptibility to
      measles by age. The effective reproduction numbers for each district and
      strategic health authority were calculated and possible outbreak sizes estimated.
      RESULTS: In 2004/05, about 1.9 million school children and 300,000 pre-school
      children were recorded as incompletely vaccinated against measles in England,
      including more than 800,000 children completely unvaccinated. Based on this,
      approximately 1.3 million children aged 2-17 years were susceptible to measles.
      In 14 of the 99 districts, the level of susceptibility is sufficiently high for R
      to exceed 1, indicating the potential for sustained measles transmission. Eleven
      of these districts are in London. Our model suggests that the potential exists
      for an outbreak of up to 100,000 cases. These results are sensitive to the
      accuracy of reported vaccination coverage data. CONCLUSION: Our analysis
      identified several districts with the potential for sustaining measles
      transmission. Many London areas remain at high risk even allowing for
      considerable under-reporting of coverage. Primary care trusts should ensure that
      accurate systems are in place to identify unimmunised children and to offer catch
      up immunisation for those not up to date for MMR.

PMID- 18822143
TI  - Evidence of inflammatory immune signaling in chronic fatigue syndrome: A pilot
      study of gene expression in peripheral blood.
AB  - BACKGROUND: Genomic profiling of peripheral blood reveals altered immunity in
      chronic fatigue syndrome (CFS) however interpretation remains challenging without
      immune demographic context. The object of this work is to identify modulation of
      specific immune functional components and restructuring of co-expression networks
      characteristic of CFS using the quantitative genomics of peripheral blood.
      METHODS: Gene sets were constructed a priori for CD4+ T cells, CD8+ T cells,
      CD19+ B cells, CD14+ monocytes and CD16+ neutrophils from published data. A group
      of 111 women were classified using empiric case definition (U.S. Centers for
      Disease Control and Prevention) and unsupervised latent cluster analysis (LCA).
      Microarray profiles of peripheral blood were analyzed for expression of leukocyte
      specific gene sets and characteristic changes in co-expression identified from
      topological evaluation of linear correlation networks. RESULTS: Median expression
      for a set of 6 genes preferentially up-regulated in CD19+ B cells was
      significantly lower in CFS (p = 0.01) due mainly to PTPRK and TSPAN3 expression.
      Although no other gene set was differentially expressed at p < 0.05, patterns of
      co-expression in each group differed markedly. Significant co-expression of CD14+
      monocyte with CD16+ neutrophil (p = 0.01) and CD19+ B cell sets (p = 0.00)
      characterized CFS and fatigue phenotype groups. Also in CFS was a significant
      negative correlation between CD8+ and both CD19+ up-regulated (p = 0.02) and NK
      gene sets (p = 0.08). These patterns were absent in controls. CONCLUSION:
      Dissection of blood microarray profiles points to B cell dysfunction with
      coordinated immune activation supporting persistent inflammation and antibody
      mediated NK cell modulation of T cell activity. This has clinical implications as
      the CD19+ genes identified could provide robust and biologically meaningful basis
      for the early detection and unambiguous phenotyping of CFS.

PMID- 18822144
TI  - Phylogenetic patterns and conservation among North American members of the genus
      Agalinis (Orobanchaceae).
AB  - BACKGROUND: North American Agalinis Raf. species represent a taxonomically
      challenging group and there have been extensive historical revisions at the
      species, section, and subsection levels of classification. The genus contains
      many rare species, including the federally listed endangered species Agalinis
      acuta. In addition to evaluating the degree to which historical classifications
      at the section and subsection levels are supported by molecular data sampled from
      79 individuals representing 29 Agalinis species, we assessed the monophyly of 27
      species by sampling multiple individuals representing different populations of
      those species. Twenty-one of these species are of conservation concern in at
      least some part of their range. RESULTS: Phylogenetic relationships estimated
      using maximum likelihood analyses of seven chloroplast DNA loci (aligned length =
      11,076 base pairs (bp) and the nuclear ribosomal DNA ITS (internal transcribed
      spacer) locus (733 bp); indicated no support for the historically recognized
      sections except for Section Erectae. Our results suggest that North American
      members of the genus comprise six major lineages, however we were not able to
      resolve branching order among many of these lineages. Monophyly of 24 of the 29
      sampled species was supported based on significant branch lengths of and high
      bootstrap support for subtending branches. However, there was no statistical
      support for the monophyly of A. acuta with respect to Agalinis tenella and
      Agalinis decemloba. Although most species were supported, deeper relationships
      among many species remain ambiguous. CONCLUSION: The North American Agalinis
      species sampled form a well supported, monophyletic group within the family
      Orobanchaceae relative to the outgroups sampled. Most hypotheses regarding
      section- and subsection-level relationships based on morphology were not
      supported and taxonomic revisions are warranted. Lack of support for monophyly of
      Agalinis acuta leaves the important question regarding its taxonomic status
      unanswered. Lack of resolution is potentially due to incomplete lineage sorting
      of ancestral polymorphisms among recently diverged species; however the gene
      regions examined did distinguish among almost all other species in the genus. Due
      to the important policy implications of this finding we are further evaluating
      the evolutionary distinctiveness of A. acuta using morphological data and loci
      with higher mutation rates.

PMID- 18822145
TI  - Neuraminidase activity provides a practical read-out for a high throughput
      influenza antiviral screening assay.
AB  - BACKGROUND: The emergence of influenza strains that are resistant to commonly
      used antivirals has highlighted the need to develop new compounds that target
      viral gene products or host mechanisms that are essential for effective virus
      replication. Existing assays to identify potential antiviral compounds often use
      high throughput screening assays that target specific viral replication steps. To
      broaden the search for antivirals, cell-based replication assays can be
      performed, but these are often labor intensive and have limited throughput.
      RESULTS: We have adapted a traditional virus neutralization assay to develop a
      practical, cell-based, high throughput screening assay. This assay uses viral
      neuraminidase (NA) as a read-out to quantify influenza replication, thereby
      offering an assay that is both rapid and sensitive. In addition to identification
      of inhibitors that target either viral or host factors, the assay allows
      simultaneous evaluation of drug toxicity. Antiviral activity was demonstrated for
      a number of known influenza inhibitors including amantadine that targets the M2
      ion channel, zanamivir that targets NA, ribavirin that targets IMP dehydrogenase,
      and bis-indolyl maleimide that targets protein kinase A/C. Amantadine-resistant
      strains were identified by comparing IC50 with that of the wild-type virus.
      CONCLUSION: Antivirals with specificity for a broad range of targets are easily
      identified in an accelerated viral inhibition assay that uses NA as a read-out of
      replication. This assay is suitable for high throughput screening to identify
      potential antivirals or can be used to identify drug-resistant influenza strains.

PMID- 18822146
TI  - Modeling gene-by-environment interaction in comorbid depression with alcohol use
      disorders via an integrated bioinformatics approach.
AB  - BACKGROUND: Comorbidity of Major Depressive Disorder (depression) and Alcohol Use
      Disorders (AUD) is well documented. Depression, AUD, and the comorbidity of
      depression with AUD show evidence of genetic and environmental influences on
      susceptibility. We used an integrated bioinformatics approach, mining available
      data in multiple databases, to develop and refine a model of gene-by-environment
      interaction consistent with this comorbidity. METHODS: We established the
      validity of a genetic model via queries against NCBI databases, identifying and
      validating TNF (Tumor Necrosis Factor) and MTHFR (Methylenetetrahydrofolate
      Reductase) as candidate genes. We used the PDG-ACE algorithm (Prioritizing
      Disease Genes by Analysis of Common Elements) to show that TNF and MTHFR share
      significant commonality and that this commonality is consistent with a response
      to environmental exposure to ethanol. Finally, we used MetaCore from GeneGo, Inc.
      to model a gene-by-environment interaction consistent with the data. RESULTS: TNF
      Alpha Converting Enzyme (TACE) activity is suppressed by ethanol exposure,
      resulting in reduced TNF signaling. TNF binds to TNF receptors, initiating signal
      transduction pathways that activate MTHFR expression. MTHFR is an essential
      enzyme in folate metabolism and reduced folate levels are associated with both
      AUD and depression. Integrating these pieces of information our model shows how
      excessive alcohol use would be expected to lead to reduced TNF signaling, reduced
      MTHFR expression, and increased susceptibility to depression. CONCLUSION: The
      proposed model provides a novel hypothesis on the genetic etiology of comorbid
      depression with AUD, consistent with established clinical and biochemical data.
      This analysis also provides an example of how an integrated bioinformatics
      approach can maximize the use of available biomedical data to improve our
      understanding of complex disease.

PMID- 18822147
TI  - Neural networks for genetic epidemiology: past, present, and future.
AB  - During the past two decades, the field of human genetics has experienced an
      information explosion. The completion of the human genome project and the
      development of high throughput SNP technologies have created a wealth of data;
      however, the analysis and interpretation of these data have created a research
      bottleneck. While technology facilitates the measurement of hundreds or thousands
      of genes, statistical and computational methodologies are lacking for the
      analysis of these data. New statistical methods and variable selection strategies
      must be explored for identifying disease susceptibility genes for common, complex
      diseases. Neural networks (NN) are a class of pattern recognition methods that
      have been successfully implemented for data mining and prediction in a variety of
      fields. The application of NN for statistical genetics studies is an active area
      of research. Neural networks have been applied in both linkage and association
      analysis for the identification of disease susceptibility genes.In the current
      review, we consider how NN have been used for both linkage and association
      analyses in genetic epidemiology. We discuss both the successes of these initial
      NN applications, and the questions that arose during the previous studies.
      Finally, we introduce evolutionary computing strategies, Genetic Programming
      Neural Networks (GPNN) and Grammatical Evolution Neural Networks (GENN), for
      using NN in association studies of complex human diseases that address some of
      the caveats illuminated by previous work.

PMID- 18822148
TI  - Filling the gap between biology and computer science.
AB  - This editorial introduces BioData Mining, a new journal which publishes research
      articles related to advances in computational methods and techniques for the
      extraction of useful knowledge from heterogeneous biological data. We outline the
      aims and scope of the journal, introduce the publishing model and describe the
      open peer review policy, which fosters interaction within the research community.

PMID- 18822149
TI  - Musculoskeletal ultrasound imaging of the plantar forefoot in patients with
      rheumatoid arthritis: inter-observer agreement between a podiatrist and a
      radiologist.
AB  - BACKGROUND: The use of musculoskeletal ultrasound (MSUS) in the diagnosis and
      management of foot and ankle musculoskeletal pathology is increasing. Due to the
      wide use of MSUS and the depth and breadth of training required new proposals
      advocate tailored learning of the technique to discrete fields of practice. The
      aims of the study were to evaluate the inter-observer agreement between a MSUS
      radiologist and a podiatrist, who had completed basic skills training in MSUS, in
      the MSUS assessment of the forefoot of patients with Rheumatoid Arthritis.
      METHODS: A consecutive sample of thirty-two patients with rheumatoid arthritis
      was assessed for presence of synovitis, erosions and bursitis within the forefoot
      using MSUS. All MSUS assessments were performed independently on the same day by
      a podiatrist and one of two Consultant Radiologists experienced in MSUS. RESULTS:
      Moderate agreement on image acquisition and interpretation was achieved for
      bursitis (kappa 0.522; p < 0.01) and erosions (kappa 0.636; p < 0.01) and fair
      agreement for synovitis (kappa 0.216; p < 0.05) during the primary assessments.
      Following a further training session, substantial agreement (kappa 0.702) between
      the two investigators was recorded. The sensitivity of the podiatrist using MSUS
      was 82.4% for detection of bursitis, 83.0% for detection of erosion and 84.0% for
      detection of synovitis. Specificity of the podiatrist using MSUS was 88.9% for
      detection of bursitis, 80.7% for detection of erosion and 35.9% for detection of
      synovitis. CONCLUSION: This study demonstrated good inter-observer agreement
      between a podiatrist and radiologist on MSUS assessment of the forefoot,
      particularly for bursitis and erosions, in patients with rheumatoid arthritis.
      There is scope to further evaluate and consider the role of podiatrists in the
      MSUS imaging of the foot following appropriate training and also in the
      development of reliable protocols for MSUS assessment of the foot.

PMID- 18822150
TI  - Uncovering mechanisms of transcriptional regulations by systematic mining of cis
      regulatory elements with gene expression profiles.
AB  - BACKGROUND: Contrary to the traditional biology approach, where the expression
      patterns of a handful of genes are studied at a time, microarray experiments
      enable biologists to study the expression patterns of many genes simultaneously
      from gene expression profile data and decipher the underlying hidden biological
      mechanism from the observed gene expression changes. While the statistical
      significance of the gene expression data can be deduced by various methods, the
      biological interpretation of the data presents a challenge. RESULTS: A method,
      called CisTransMine, is proposed to help infer the underlying biological
      mechanisms for the observed gene expression changes in microarray experiments.
      Specifically, this method will predict potential cis-regulatory elements in
      promoter regions which could regulate gene expression changes. This approach
      builds on the MotifADE method published in 2004 and extends it with two
      modifications: up-regulated genes and down-regulated genes are tested separately
      and in addition, tests have been implemented to identify combinations of
      transcription factors that work synergistically. The method has been applied to a
      genome wide expression dataset intended to study myogenesis in a mouse C2C12 cell
      differentiation model. The results shown here both confirm the prior biological
      knowledge and facilitate the discovery of new biological insights. CONCLUSION:
      The results validate that the CisTransMine approach is a robust method to uncover
      the hidden transcriptional regulatory mechanisms that can facilitate the
      discovery of mechanisms of transcriptional regulation.

PMID- 18822151
TI  - Clustering-based approaches to SAGE data mining.
AB  - Serial analysis of gene expression (SAGE) is one of the most powerful tools for
      global gene expression profiling. It has led to several biological discoveries
      and biomedical applications, such as the prediction of new gene functions and the
      identification of biomarkers in human cancer research. Clustering techniques have
      become fundamental approaches in these applications. This paper reviews relevant
      clustering techniques specifically designed for this type of data. It places an
      emphasis on current limitations and opportunities in this area for supporting
      biologically-meaningful data mining and visualisation.

PMID- 18822152
TI  - Growing pains: contemporary knowledge and recommended practice.
AB  - BACKGROUND: Leg pain in children, described as growing pains, is a frequent
      clinical presentation seen by an array of health care professionals. Described
      since 1823, growing pains continues to puzzle practitioners, yet diagnostic
      criteria and evidence based treatment is available. METHODS: The medical
      literature has been searched exhaustively to access all articles (English
      language) pertaining to leg pains in children which are ascribed to being
      'growing pains'. RESULTS: The literature, whilst plentiful in quantity and
      spanning two centuries, is generally replete with reiterated opinion and anecdote
      and lacking in scientific rigour. The author searched 45 articles for relevance,
      determined according to title, abstract and full text, resulting in a yield of 22
      original studies and 23 review articles. From the original studies, one small
      (non-blinded) randomised controlled trial that focused on GP treatment with leg
      muscle stretching was found. Nine prevalence studies were found revealing
      disparate estimates. Ten cohort (some case-controlled) studies, which
      investigated pain attribute differences in affected versus unaffected groups,
      were found. One series of single case experiment designs and one animal model
      study were found. CONCLUSION: Growing pains is prevalent in young children,
      presents frequently in the health care setting where it is poorly managed and is
      continuing to be researched. A common childhood complaint, growing pains needs to
      be acknowledged and better managed in the contemporary medical setting.

PMID- 18822153
TI  - Prevalence and correlates of foot pain in a population-based study: the North
      West Adelaide health study.
AB  - BACKGROUND: Few population-based studies have examined the prevalence of foot
      pain in the general community. The aims of this study were therefore to determine
      the prevalence, correlates and impact of foot pain in a population-based sample
      of people aged 18 years and over living in the northwest region of Adelaide,
      South Australia. METHODS: The North West Adelaide Health Study is a
      representative longitudinal cohort study of n = 4,060 people randomly selected
      and recruited by telephone interview. The second stage of data collection on this
      cohort was undertaken between mid 2004 and early 2006. In this phase, information
      regarding the prevalence of musculoskeletal conditions was included. Overall, n =
      3,206 participants returned to the clinic during the second visit, and as part of
      the assessment were asked to report whether they had pain, aching or stiffness on
      most days in either of their feet. Data were also collected on body mass index
      (BMI); major medical conditions; other joint symptoms and health-related quality
      of life (the Medical Outcomes Study Short Form 36 [SF-36]). RESULTS: Overall,
      17.4% (95% confidence interval 16.2 - 18.8) of participants indicated that they
      had foot pain, aching or stiffness in either of their feet. Females, those aged
      50 years and over, classified as obese and who reported knee, hip and back pain
      were all significantly more likely to report foot pain. Respondents with foot
      pain scored lower on all domains of the SF-36 after adjustment for age, sex and
      BMI. CONCLUSION: Foot pain affects nearly one in five of people in the community,
      is associated with increased age, female sex, obesity and pain in other body
      regions, and has a significant detrimental impact on health-related quality of
      life.

PMID- 18822154
TI  - Arch height change during sit-to-stand: an alternative for the navicular drop
      test.
AB  - BACKGROUND: A study was conducted to determine the reliability and validity of a
      new foot mobility assessment method that utilizes digital images to measure the
      change in dorsal arch height measured at 50% of the length of the foot during the
      Sit-to-Stand test. METHODS: Two hundred - seventy five healthy participants
      participated in the study. The medial aspect of each foot was photographed with a
      digital camera while each participant stood with 50% body weight on each foot as
      well as in sitting for a non-weight bearing image. The dorsal arch height was
      measured at 50% of the total length of the foot on both weight bearing and non
      weight bearing images to determine the change in dorsal arch height. The
      reliability and validity of the measurements were then determined. RESULTS: The
      mean difference in dorsal arch height between non-weight bearing and weight
      bearing was 10 millimeters. The change in arch height during the Sit-to-Stand
      test was shown to have good to high levels of intra- and inter-reliability as
      well as validity using x-rays as the criterion measure. CONCLUSION: While the
      navicular drop test has been widely used as a clinical method to assess foot
      mobility, poor levels of inter-rater reliability have been reported. The results
      of the current study suggest that the change in dorsal arch height during the Sit
      to-Stand test offers the clinician a reliable and valid alternative to the
      navicular drop test.

PMID- 18822155
TI  - Normative values for the Foot Posture Index.
AB  - BACKGROUND: The Foot Posture Index (FPI) is a validated method for quantifying
      standing foot posture, and is being used in a variety of clinical settings. There
      have however, been no normative data available to date for comparison and
      reference. This study aimed to establish normative FPI reference values. METHODS:
      Studies reporting FPI data were identified by searching online databases. Nine
      authors contributed anonymised versions of their original datasets comprising
      1648 individual observations. The datasets included information relating to
      centre, age, gender, pathology (if relevant), FPI scores and body mass index
      (BMI) where available. FPI total scores were transformed to interval logit scores
      as per the Rasch model and normal ranges were defined. Comparisons between groups
      employed t-tests or ANOVA models as appropriate and data were explored
      descriptively and graphically. RESULTS: The main analysis based on a normal
      healthy population (n = 619) confirmed that a slightly pronated foot posture is
      the normal position at rest (mean back transformed FPI raw score = +4). A 'U'
      shaped relationship existed for age, with minors and older adults exhibiting
      significantly higher FPI scores than the general adult population (F = 51.07, p <
      0.001). There was no difference between the FPI scores of males and females (2.3
      versus 2.5; t = -1.44, p = 0.149). No relationship was found between the FPI and
      BMI. Systematic differences from the adult normals were confirmed in patients
      with neurogenic and idiopathic cavus (F = 216.981, p < 0.001), indicating some
      sensitivity of the instrument to detect a posturally pathological population.
      CONCLUSION: A set of population norms for children, adults and older people have
      been derived from a large sample. Foot posture is related to age and the presence
      of pathology, but not influenced by gender or BMI. The normative values
      identified may assist in classifying foot type for the purpose of research and
      clinical decision making.

PMID- 18822156
TI  - Welcome to Journal of Foot and Ankle Research: a new open access journal for foot
      health professionals.
AB  - Journal of Foot and Ankle Research (JFAR) is a new, open access, peer-reviewed
      online journal that encompasses all aspects of policy, organisation, delivery and
      clinical practice related to the assessment, diagnosis, prevention and management
      of foot and ankle disorders. JFAR will cover a wide range of clinical subject
      areas, including diabetology, paediatrics, sports medicine, gerontology and
      geriatrics, foot surgery, physical therapy, dermatology, wound management,
      radiology, biomechanics and bioengineering, orthotics and prosthetics, as well
      the broad areas of epidemiology, policy, organisation and delivery of services
      related to foot and ankle care. The journal encourages submission from all health
      professionals who manage lower limb conditions, including podiatrists, nurses,
      physical therapists and physiotherapists, orthopaedists, manual therapists,
      medical specialists and general medical practitioners, as well as health service
      researchers concerned with foot and ankle care. All manuscripts will undergo open
      peer review, and all accepted manuscripts will be freely available on-line using
      the open access platform of BioMed Central.

PMID- 18822157
TI  - Tobacco use and asking prices of used cars: prevalence, costs, and new
      opportunities for changing smoking behavior.
AB  - Secondhand smoke (SHS) causes premature death and disease in children and
      adults, and the scientific evidence indicates that there is no risk-free level of
      exposure to SHS. Smoking tobacco in a car can pollute the microenvironment of the
      car with residual SHS, leaving telltale signs to potential buyers (e.g., odor,
      used ash tray). This study examined (a) the proportion of used cars sold in the
      private party market that may be polluted with tobacco smoke and (b) whether
      asking prices of smoker and nonsmoker cars differed for cars of otherwise
      equivalent value. A random sample of 1,642 private party sellers were interviewed
      by telephone, and content analyses of print advertisements were conducted.
      Findings indicate that 22% of used cars were advertised by smokers or had been
      smoked in during the previous year. Among nonsmokers, 94% did not allow smoking
      in their car during the past year. Only 33% of smokers had the same restrictions.
      The smoking status of the seller and tobacco use in the car were significantly (p
      < .01) associated with the asking price independent of a car's Kelley Blue Book
      value (KBB). Used nonsmoker cars were offered at a considerable premium above
      their KBB value (>11%) and above comparable smoker cars (7-9%). These findings
      suggest that community preferences are affecting the value of smoke-free cars.
      New directions for research, tobacco control policies, and health education are
      discussed to further reduce smoking behavior, to help consumers make informed
      purchasing decisions, and to protect nonsmokers from SHS exposure.

PMID- 18822158
TI  - Tobacco Induced Diseases moves to BioMed Central.
AB  - This Editorial marks the transfer of Tobacco Induced Diseases to BioMed
      Central's publishing platform.

PMID- 18822159
TI  - The Framework Convention on Tobacco Control (FCTC) and Japanese anti-tobacco
      measures.
AB  - Japanese anti-tobacco measures are reviewed and checked the relationship between
      the FCTC and its changes. Japan is making efforts to follow the FCTC, but it is
      insufficient and present anti-tobacco measures seem to have only a little impact
      on decreasing smoking rates. More effective measures should be developed for
      reducing smoking rates and for making smoke-free society.

PMID- 18822160
TI  - Mitogenic and functional responses by nicotine and hydrogen peroxide in AR42J
      cells: a comparative study.
AB  - The aim of the current study was to investigate the oxidative effects of
      nicotine by examining the mitogenic and functional responses in AR42J cells. As a
      control and for comparison, hydrogen peroxide (H2O2) was used as a source of
      known oxidative biomarker. Responses were examined by determining cell
      proliferation through the activation of ERK signaling, basal and CCK-stimulated
      cell function and measuring lipid peroxidation. AR42J cells have been exposed to
      either a non-cytotoxic dose of 20 muM H2O2 for 15 min or to 100 muM of nicotine
      for 3 min respectively. Nicotine and H2O2 at these dose and time intervals
      produced similar levels of malondialdyde (MDA) production and p-ERK1/2
      activation. Immunofluorescence studies employing specific antibody to p-ERK1/2
      confirmed the latter. Nicotine-induced increase in the proliferation of AR42J
      cells was significantly higher in comparison to H2O2 exposed cells. CCK
      stimulated cell function induced by nicotine was significantly higher in AR42J
      cells as compared to the response by H2O2. These results suggest that nicotine-
      induced mitogenic and functional response in AR42J cells are associated with ERK
      signaling and increase in reactive oxygen species production. The data suggests
      that nicotine-induced mitogenic response in AR42J cells closely identifies the
      response induced by an oxidative biomarker.

PMID- 18822161
TI  - Identification of bacterial and fungal components in tobacco and tobacco smoke.
AB  - The microbiological composition of tobacco products was studied using culture
      and chemical analysis (of tobacco leaves) or chemical analysis only (tobacco and
      tobacco smoke). The chemical analyses utilized gas chromatography-tandem mass
      spectrometry for determining 3-hydroxy fatty acids, muramic acid, and ergosterol
      as markers of respectively lipopolysaccharide (LPS), peptidoglycan, and fungal
      biomass. Mesophilic bacteria dominated in both fresh and cured tobacco leaves; a
      range of additional bacteria and fungi were also found albeit in minor amounts.
      The peptidoglycan and LPS concentrations were approximately the same in tobacco
      leaves as in cigarette tobacco. The concentrations of the measured microbial
      components were much lower in some cigarettes locally produced in China, Korea,
      and Vietnam than in cigarettes of international brands purchased in the same
      countries, and the concentrations in the smoke were in general agreement with the
      concentrations in cigarette tobacco. No differences in microbial load in tobacco
      of "light" and "full flavor" cigarettes were seen. Storing cigarettes at high
      humidity resulted in elevated levels of fungi in the cigarette tobacco leading to
      increased ergosterol concentrations in the smoke. The fact that tobacco smoke is
      a bioaerosol may help to explain the high prevalence of respiratory disorders
      among smokers and non-smokers exposed to second hand smoke since the same
      symptoms are also commonly associated with exposure to bioaerosols.

PMID- 18822162
TI  - Plantar calcaneal spurs in older people: longitudinal traction or vertical
      compression?
AB  - BACKGROUND: Plantar calcaneal spurs are common, however their pathophysiology is
      poorly understood. This study aimed to evaluate the prevalence and correlates of
      plantar calcaneal spurs in a large sample of older people. METHODS: Weightbearing
      lateral foot radiographs of 216 people (140 women and 76 men) aged 62 to 94 years
      (mean age 75.9, SD 6.6) were examined for plantar calcaneal and Achilles tendon
      spurs. Associations between the presence of spurs and sex, body mass index,
      radiographic measures of foot posture, self-reported co-morbidities and current
      or previous heel pain were then explored. RESULTS: Of the 216 participants, 119
      (55%) had at least one plantar calcaneal spur and 103 (48%) had at least one
      Achilles tendon spur. Those with plantar calcaneal spurs were more likely to have
      Achilles tendon spurs (odds ratio [OR] = 2.0, 95% confidence interval [CI] 1.2 to
      3.5). Prevalence of spurs did not differ according to sex. Participants with
      plantar calcaneal spurs were more likely to be obese (OR = 7.9, 95% CI 3.6 to
      17.0), report osteoarthritis (OR = 2.6, 95% CI 1.6 to 4.8) and have current or
      previous heel pain (OR = 4.6, 95% CI 2.3 to 9.4). No relationship was found
      between the presence of calcaneal spurs and radiographic measures of foot
      posture. CONCLUSION: Calcaneal spurs are common in older men and women and are
      related to obesity, osteoarthritis and current or previous heel pain, but are
      unrelated to radiographic measurements of foot posture. These findings support
      the theory that plantar calcaneal spurs may be an adaptive response to vertical
      compression of the heel rather than longitudinal traction at the calcaneal
      enthesis.

PMID- 18822163
TI  - Predictors of podiatry utilisation in Australia: the North West Adelaide Health
      Study.
AB  - BACKGROUND: Foot problems are highly prevalent in the community; however no large
      population-based studies have examined the characteristics of those who do and do
      not access podiatry services in Australia. The aim of this study was to explore
      patterns of podiatry utilisation in a population-based sample of people aged 18
      years and over living in the northwest region of Adelaide, South Australia.
      METHODS: The North West Adelaide Health Study is a representative longitudinal
      cohort study of 4,060 people randomly selected and recruited by telephone
      interview. The interview included questions regarding healthcare service
      utilisation in the past year. Data were also collected on education, income and
      major medical conditions. RESULTS: Overall, 9.5% of the total sample and 17.7% of
      those who reported foot pain had attended a podiatrist in the past year.
      Participants who had accessed podiatry treatment were more likely to be female,
      be aged over 45 years, be obese, and have major chronic medical conditions
      (osteoporosis, osteoarthritis, diabetes, cardiovascular disease and high blood
      pressure). Those who reported foot pain but had not accessed a podiatrist were
      more likely to be male and be aged 20 to 34 years. CONCLUSION: Only a small
      proportion of people who report foot pain have accessed podiatry services in the
      past year. There is a need to further promote podiatry services to the general
      community, particularly to men and younger people.

PMID- 18822164
TI  - Designing a tobacco counter-marketing campaign for African American youth.
AB  - The objectives of this qualitative study were to: a) identify common marketing
      themes and tactics used by the tobacco industry to entice African Americans
      (AA's) and youth to initiate and maintain smoking behavior, especially smoking
      mentholated brands of cigarettes, and b) determine AA youths' knowledge,
      attitudes, intentions, and beliefs about smoking and the tobacco industry.
      Together, these activities could aid in the development of effective tobacco
      counter-marketing campaigns for AA youth. Using publicly available tobacco
      industry documents, computerized searches using standardized keywords were run
      and results were cataloged and analyzed thematically. Subsequently, 5 focus
      groups were conducted with n = 28 AA middle school-aged youth. Results suggest
      that the tobacco industry consistently recruited new AA smokers through a variety
      of means, including social and behavioral marketing studies and targeted media
      and promotional campaigns in predominantly AA, urban, and low income areas. AA
      youth interviewed in this study were largely unaware of these tactics, and
      reacted negatively against the industry upon learning of them. Youth tended to
      externalize control over tobacco, especially within the AA community. In
      designing a counter-marketing campaign for this population, partnering knowledge
      of tobacco industry practices with youth needs and community resources will
      likely increase their effectiveness.

PMID- 18822165
TI  - A profile of teen smokers who volunteered to participate in school-based smoking
      intervention.
AB  - OBJECTIVES: Although a number of population-based studies have examined the
      characteristics of teens who attempt to quit smoking, few have identified the
      characteristics of youth who participate in structured cessation interventions,
      particularly those with demonstrated effectiveness. The purpose of the present
      study is to describe the sociodemographic and smoking-related characteristics of
      teen smokers who participated in the American Lung Association's Not On Tobacco
      (N-O-T) program, spanning eight years. N-O-T is the most widely used teen smoking
      cessation program in the nation. METHODS: Drawn from multiple statewide N-O-T
      studies, this investigation examined data from 5,892 teen smokers ages 14-19 who
      enrolled in N-O-T between 1998-2006. We demonstrate similarities and differences
      between N-O-T findings and existing data from representative samples of US teen
      smokers where available and relevant. RESULTS: N-O-T teens started smoking
      earlier, were more likely to be poly-tobacco users, were more dependent on
      nicotine, had made more previous attempts to quit, and were more deeply embedded
      in smoking contexts than comparative samples of teen smokers. Additionally, N-O-T
      teens were moderately ready to quit smoking, believed important people in their
      lives would support their quit efforts, yet had deficits in their confidence with
      quitting. CONCLUSION: This profile of N-O-T teens can guide efforts for targeted
      recruitment strategies to enhance intervention reach for teen smoking cessation.
      Findings provide guidance for marketing and recruitment efforts of intensive,
      school-based cessation interventions among established teen smokers, particularly
      those who want to quit. Study results may shed light upon who is and is not
      enrolling in N-O-T.

PMID- 18822166
TI  - Threshold for detection of diabetic peripheral sensory neuropathy using a range
      of research grade monofilaments in persons with Type 2 diabetes mellitus.
AB  - AIMS: To identify the threshold of reduced sensory perception in Type 2 diabetes
      mellitus (Type 2 DM) using a range of research grade monofilaments. METHODS:
      Three groups of participants were recruited into a between subject, cross
      sectional study. Group 1(NEW), persons with Type 2 DM diagnosed for less than 2
      years (n = 80); Group 2 (EST) persons with Type 2 DM diagnosed for more than 2
      years (n = 91), and Group 3, a Comparison group without Type 2 DM (n = 73),
      resulted in a total study population, n = 244. Research grade monofilaments (2,
      4, 6, 8 and 10-gram) were employed using standardised protocol, at 6 sites on the
      plantar aspect of both feet. The demographic and anthropometric measures of
      gender, age, height, weight, body mass index (BMI), blood pressure and duration
      of Type 2 DM since diagnosis (if applicable) of the participants were analysed.
      RESULTS: Perception of the research grade monofilaments differed significantly
      between the 3 groups (p < 0.05). The 6-gram monofilament was found to be the
      threshold of normal perception, based on 90% of the Comparison group perceiving
      the 6-gram monofilament at all sites in contrast to 64% of NEW and 48% of EST
      groups. CONCLUSION: The 6-gram monofilament was identified as the threshold of
      normal sensory perception. Inability to perceive the 6-gram monofilament
      indicates, when using the method described in this study, that diminution of
      sensory perception is evident. Employing a range of monofilaments, 6, 8 and 10
      grams in Type 2 DM foot screening would allow the clinical detection of
      deteriorating sensory perception and enable implementation of foot protection
      strategies at an earlier stage than is currently practised.

PMID- 18822167
TI  - The historical decline of tobacco smoking among United States physicians: 1949
      1984.
AB  - BACKGROUND: Tobacco use became an ingrained habit in the United States (US)
      following the First World War and a large proportion of physicians, similar to
      the general population, were smokers. The period from 1949 to 1984 was a pivotal
      era of change however, as the medical profession, like the society it served,
      became increasingly aware of the dangers that tobacco incurred for health.
      METHODS: An extensive review targeted all manuscripts published in academic
      journals between 1949 and 1984 that related to tobacco smoking among US
      physicians. The study was undertaken in 2007-08 with an internet search of
      relevant medical databases, after which time the reference lists of manuscripts
      were also examined to find additional articles. RESULTS: A total of 57
      manuscripts met the inclusion criteria. From a research perspective, the
      methodology and coverage of smoking surveys ranged from detailed national
      investigations, to local medical association surveys, and journal readership
      questionnaires. From a historical perspective, it can be seen that by the 1950s
      many US physicians had begun questioning the safety of tobacco products, and by
      the 1960s and 1970s, this had resulted in a continuous decline in tobacco use. By
      the 1980s, few US physicians were still smoking, and many of their younger
      demographic had probably never smoked at all. CONCLUSION: Although the quality
      and coverage of historical surveys varied over time, a review of their main
      results indicates a clear and consistent decline in tobacco use among US
      physicians between 1949 and 1984. Much can be learned from this pivotal era of
      public health, where the importance of scientific knowledge, professional
      leadership and social responsibility helped set positive examples in the fight
      against tobacco.

PMID- 18822168
TI  - Acral lentiginous melanoma of the foot and ankle: A case series and review of the
      literature.
AB  - BACKGROUND: Acral lentiginous melanoma (ALM) is an uncommon, cutaneous malignant
      tumour which may arise on the foot. Its relative rarity, atypical appearance and
      late presentation frequently serve as poor prognostic indicators. METHODS: At a
      tertiary skin tumour centre, a retrospective review was undertaken of all
      patients diagnosed with the tumour at the level of ankle or below. RESULTS: Over
      a six year period, 27 cases (20 female, 7 male) were identified with positive
      histology confirming the disease. The age ranged from 35-96 years of age (mean
      62.7 years). The majority of the cohort were white (59%) with plantar lesions
      (62%). 33% of patients were initially were diagnosed incorrectly. The average
      time taken from the point of recognition, by the patient, to the lesion being
      correctly diagnosed was around 13.5 months. CONCLUSION: Earlier diagnosis of ALM
      requires education at both a patient and practitioner level.

PMID- 18822169
TI  - Foot and ankle surgery in Australia: a descriptive analysis of the Medicare
      Benefits Schedule database, 1997-2006.
AB  - BACKGROUND: Foot and ankle problems are highly prevalent in the general community
      and a substantial proportion of people seek surgical treatment to alleviate foot
      pain and deformity. However, the epidemiology of foot and ankle surgery has not
      been examined in detail. Therefore, the aim of this study was to examine patterns
      and costs of private sector foot surgery provision in Australia. METHODS: Data
      pertaining to all foot and ankle surgical procedures for the calendar years 1997
      2006 were extracted from the Australian Medicare Benefits Schedule (MBS) database
      and were cross-tabulated by sex and age. Descriptive analyses were undertaken to
      assess sex and age differences in the number and type of procedures performed and
      to assess for temporal trends over the ten year assessment period. The total cost
      to Medicare of subsiding surgeons' fees in 2006 was also determined. RESULTS:
      During the 1997-2006 period, 996,477 surgical procedures were performed on the
      foot and ankle by private surgeons in Australia. Approximately equal numbers of
      procedures were performed on males (52%) and females (48%). However, males were
      more likely to undergo toenail, ankle, clubfoot, tarsal coalition and congenital
      vertical talus surgery, whereas females were more likely to undergo lesser toe,
      first metatarsophalangeal joint (MPJ), neuroma, heel, rearfoot and lesser MPJ
      surgery. The total number of procedures was stable over the assessment period,
      however there was a relative increase in the number of procedures performed on
      people aged over 55 years. The total contribution of Medicare to subsiding
      surgeons' fees for procedures performed in 2006 was $14 M. CONCLUSION: Foot and
      ankle surgery accounts for a considerable degree of healthcare expenditure in
      Australia, and the number of procedures in those aged over 55 years is
      increasing. Given the ageing demographics of the Australian population, the
      future public health and economic impact of foot morbidity is likely to be
      substantial. Strategies need to be implemented to ensure that the surgical labour
      force is adequate to address this increasing demand.

PMID- 18822170
TI  - Effectiveness of artemisinin-based combination therapy used in the context of
      home management of malaria: a report from three study sites in sub-Saharan
      Africa.
AB  - BACKGROUND: The use of artemisinin-based combination therapy (ACT) at the
      community level has been advocated as a means to increase access to effective
      antimalarial medicines by high risk groups living in underserved areas, mainly in
      sub-Saharan Africa. This strategy has been shown to be feasible and acceptable to
      the community. However, the parasitological effectiveness of ACT when dispensed
      by community medicine distributors (CMDs) within the context of home management
      of malaria (HMM) and used unsupervised by caregivers at home has not been
      evaluated. METHODS: In a sub-set of villages participating in a large-scale study
      on feasibility and acceptability of ACT use in areas of high malaria transmission
      in Ghana, Nigeria and Uganda, thick blood smears and blood spotted filter paper
      were prepared from finger prick blood samples collected from febrile children
      between six and 59 months of age reporting to trained CMDs for microscopy and PCR
      analysis. Presumptive antimalarial treatment with ACT (artesunate-amodiaquine in
      Ghana, artemether-lumefantrine in Nigeria and Uganda) was then initiated. Repeat
      finger prick blood samples were obtained 28 days later for children who were
      parasitaemic at baseline. For children who were parasitaemic at follow-up, PCR
      analyses were undertaken to distinguish recrudescence from re-infection. The
      extent to which ACTs had been correctly administered was assessed through
      separate household interviews with caregivers having had a child with fever in
      the previous two weeks. RESULTS: Over a period of 12 months, a total of 1,740
      children presenting with fever were enrolled across the study sites. Patent
      parasitaemia at baseline was present in 1,189 children (68.3%) and varied from
      60.1% in Uganda to 71.1% in Ghana. A total of 606 children (51% of infected
      children) reported for a repeat test 28 days after treatment. The crude
      parasitological failure rate varied from 3.7% in Uganda (C.I. 1.2%-6.2%) to 41.8%
      in Nigeria (C.I. 35%-49%). The PCR adjusted parasitological cure rate was greater
      than 90% in all sites, varying from 90.9% in Nigeria (C.I. 86%-95%) to 97.2% in
      Uganda (C.I. 95%-99%). Reported adherence to correct treatment in terms of dose
      and duration varied from 81% in Uganda (C.I. 67%-95%) to 97% in Ghana (C.I. 95%
      99%) with an average of 94% (C.I. 91%-97%). CONCLUSION: While follow-up rates
      were low, this study provides encouraging data on parasitological outcomes of
      children treated with ACT in the context of HMM and adds to the evidence base for
      HMM as a public health strategy as well as for scaling-up implementation of HMM
      with ACTs.

PMID- 18822171
TI  - Decreased levels of the gelsolin plasma isoform in patients with rheumatoid
      arthritis.
AB  - INTRODUCTION: Gelsolin is an intracellular actin-binding protein involved in cell
      shape changes, cell motility, and apoptosis. An extracellular gelsolin isoform,
      plasma gelsolin circulates in the blood of healthy individuals at a concentration
      of 200 +/- 50 mg/L and has been suggested to be a key component of an
      extracellular actin-scavenging system during tissue damage. Levels of plasma
      gelsolin decrease during acute injury and inflammation, and administration of
      recombinant plasma gelsolin to animals improves outcomes following sepsis or burn
      injuries. In the present study, we investigated plasma gelsolin in patients with
      rheumatoid arthritis. METHODS: Circulating and intra-articular levels of plasma
      gelsolin were measured in 78 patients with rheumatoid arthritis using a
      functional (pyrene-actin nucleation) assay and compared with 62 age- and gender
      matched healthy controls. RESULTS: Circulating plasma gelsolin levels were
      significantly lower in patients with rheumatoid arthritis compared with healthy
      controls (141 +/- 32 versus 196 +/- 40 mg/L, P = 0.0002). The patients' intra
      articular plasma gelsolin levels were significantly lower than in the paired
      plasma samples (94 +/- 24 versus 141 +/- 32 mg/L, P = 0.0001). Actin was detected
      in the synovial fluids of all but four of the patients, and immunoprecipitation
      experiments identified gelsolin-actin complexes. CONCLUSIONS: The plasma isoform
      of gelsolin is decreased in the plasma of patients with rheumatoid arthritis
      compared with healthy controls. The reduced plasma concentrations in combination
      with the presence of actin and gelsolin-actin complexes in synovial fluids
      suggest a local consumption of this potentially anti-inflammatory protein in the
      inflamed joint.

PMID- 18822172
TI  - European trial of free light chain removal by extended haemodialysis in cast
      nephropathy (EuLITE): a randomised control trial.
AB  - BACKGROUND: Renal failure is a frequent complication of multiple myeloma and when
      severe is associated with a greatly increased morbidity and mortality. The
      principal cause of severe renal failure is cast nephropathy, a direct consequence
      of high concentrations of monoclonal free light chains (FLCs) in patients' sera.
      FLC removal by extended haemodialysis, using a high cut-off dialyser, has
      recently been described as a novel therapeutic option. METHODS: The EUropean
      trial of free LIght chain removal by exTEnded haemodialysis in cast nephropathy
      (EuLITE) trial is a prospective, randomised, multicentre, open label clinical
      trial to investigate the clinical benefits of FLC removal haemodialysis in
      patients with cast nephropathy, dialysis dependent acute renal failure and de
      novo multiple myeloma. Recruitment commenced in May 2008. In total, 90 patients
      will be recruited. Participants will be randomised, centrally, upon enrolment, to
      either trial chemotherapy and FLC removal haemodialysis or trial chemotherapy and
      standard high flux haemodialysis. Trial chemotherapy consists of bortezomib,
      doxorubicin and dexamethasone. FLC removal haemodialysis is undertaken with two
      Gambro HCO 1100 dialysers in series using an intensive treatment schedule. The
      primary outcome for the study is independence of dialysis at 3 months. Secondary
      outcomes are: duration of dialysis, reduction in serum FLC concentrations;
      myeloma response and survival. HYPOTHESIS: FLC removal haemodialysis will
      increase the rate of renal recovery in patients with severe renal failure
      secondary to cast nephropathy in de novo multiple myeloma. TRIAL REGISTRATION:
      ISRCTN45967602.

PMID- 18822173
TI  - Prevalence of abnormal glucose metabolism in atrial fibrillation: a case control
      study in 75-year old subjects.
AB  - BACKGROUND: The prevalence of atrial fibrillation (AF) is increasing world wide
      and amongst factors that aggravate the risk is diabetes mellitus (DM), also in
      epidemic development.However, although DM is a potentially modifiable risk factor
      for AF, few, if any, studies have explored the prevalence of undiagnosed
      dysglycaemia among subjects with AF or if duration of AF are related to
      parameters of glycaemia or dysglycaemia prevalence. METHODS: In this case control
      study, amongst 75-year old subjects with and without AF, the prevalence of
      dysglycaemia, i.e., impaired fasting glycaemia, impaired glucose tolerance or DM,
      according to World Health Organisation criteria was assessed by a 75-g oral
      glucose tolerance test (OGTT). RESULTS: Prevalence of undiagnosed DM among the
      108 subjects (male/female 73/35, BMI 25.4 +/- 3.2) without and the 46
      (male/female 34/12, BMI 25.3 +/- 3.7) with AF (median AF duration five years)
      where 3.7% and 13.0%, respectively (p = 0.031, Odds ratio (OR) 3.86 (95%
      Confidence interval [CI]: 1.01, 16.25)) whereas the overall prevalence of
      dysglycaemia (prediabetes and DM) where similar (respectively 43.5% and 39.1%, p
      = 0.46, OR 0.83 [95% CI: 0.41, 1.69]). Patients with AF duration >or= 5 years had
      however a higher dysglycaemia prevalence (61.1% [DM 22.2%, prediabetes 38.9%]) as
      compared to AF duration < 5 years (25% [DM 7.1%, prediabetes 17.9%], p = 0.0014,
      OR 4.7 [95% CI: 1.30, 16.90]) or no AF (p = 0.17, OR 2.04 [95% CI: 0.73, 5.66]).
      There was also a significant correlation between the duration of AF and HbA1c (r
      = 0.408, p = 0.005) and fasting glucose levels (r = 0.353, p = 0.016).
      CONCLUSION: AF is associated with chronic hyperglycaemia amongst 75-year old
      subjects. Prediabetes and DM should be pro-actively assessed if AF duration >or=
      5 years.

PMID- 18822174
TI  - Takayasu arteritis in children.
AB  - Takayasu arteritis (TA) is a large vessel vasculitis that usually affects young
      female patients during the second and third decades of life, but has been
      reported in children as young as 24 months of age. Aim of this report was to
      describe four children (two girls) with TA, as well as summarizing main published
      studies. The mean age at presentation of our cases was 11 years (range 8-15).
      Three patients were Caucasians and one Asian. Arterial hypertension was the
      commonest mode of presentation followed by systemic symptoms. Other related
      symptoms were due to ischemia and consisted of abdomen, chest, and limb pain. An
      abdominal bruit was noted in only one patient. Inflammation markers were always
      abnormal. Angiography was performed in all cases; left subclavian artery and
      common carotid artery were more frequently involved. Renal artery stenosis was
      observed in two patients. One boy was diagnosed as having an associated immune
      deficiency (Wiskott-Aldrich syndrome). Treatment modalities included prednisone
      (n = 4), methotrexate (n = 3), and mycophenolate mofetil (MMF) (n = 1). Surgery
      was required in two patients. Follow-up ranged from 3 to 10 years since
      diagnosis. In three cases antihypertensive drugs and methotrexate were stopped,
      and prednisone was reduced to 7.5 mg/day.

PMID- 18822175
TI  - Cost-effectiveness of decompression according to Gill versus instrumented
      spondylodesis in the treatment of sciatica due to low grade spondylolytic
      spondylolisthesis: a prospective randomised controlled trial [NTR1300].
AB  - BACKGROUND: Nerve root decompression with instrumented spondylodesis is the most
      frequently performed surgical procedure in the treatment of patients with
      symptomatic low-grade spondylolytic spondylolisthesis. Nerve root decompression
      without instrumented fusion, i.e. Gill's procedure, is an alternative and less
      invasive approach. A comparative cost-effectiveness study has not been performed
      yet. We present the design of a randomised controlled trial on cost-effectiveness
      of decompression according to Gill versus instrumented spondylodesis.
      METHODS/DESIGN: All patients (age between 18 and 70 years) with sciatica or
      neurogenic claudication lasting more than 3 months due to spondylolytic
      spondylolisthesis grade I or II, are eligible for inclusion. Patients will be
      randomly allocated to nerve root decompression according to Gill, either
      unilateral or bilateral, or pedicle screw fixation with interbody fusion. The
      main primary outcome measure is the functional assessment of the patient measured
      with the Roland Disability Questionnaire for Sciatica at 12 weeks and 2 years.
      Other primary outcome measures are perceived recovery and intensity of leg pain
      and low back pain. The secondary outcome measures include, incidence of re
      operations, complications, serum creatine phosphokinase, quality of life, medical
      consumption, costs, absenteeism, work perception, depression and anxiety, and
      treatment preference. The study is a randomised prospective multicenter trial in
      which two surgical techniques are compared in a parallel group design. Patients
      and research nurse will not be blinded during the follow-up period of 2 years.
      DISCUSSION: Currently, nerve root decompression with instrumented fusion is the
      golden standard in the surgical treatment of low-grade spondylolytic
      spondylolisthesis, although scientific proof justifying instrumented
      spondylodesis over simple decompression is lacking. This trial is designed to
      elucidate the controversy in best surgical treatment of symptomatic patients with
      low-grade spondylolytic spondylolisthesis.

PMID- 18822176
TI  - Transferability and polymorphism of barley EST-SSR markers used for phylogenetic
      analysis in Hordeum chilense.
AB  - BACKGROUND: Hordeum chilense, a native South American diploid wild barley, is a
      potential source of useful genes for cereal breeding. The use of this wild
      species to increase genetic variation in cereals will be greatly facilitated by
      marker-assisted selection. Different economically feasible approaches have been
      undertaken for this wild species with limited direct agricultural use in a search
      for suitable and cost-effective markers. The availability of Expressed Sequence
      Tags (EST) derived microsatellites or simple sequence repeat (SSR) markers,
      commonly called as EST-SSRs, for barley (Hordeum vulgare) represents a promising
      source to increase the number of genetic markers available for the H. chilense
      genome. RESULTS: All of the 82 barley EST-derived SSR primer pairs tested for
      transferability to H. chilense amplified products of correct size from this
      species. Of these 82 barley EST-SSRs, 21 (26%) showed polymorphism among H.
      chilense lines. Identified polymorphic markers were used to test the
      transferability and polymorphism in other Poaceae family species with the aim of
      establishing H. chilense phylogenetic relationships. Triticum aestivum-H.
      chilense addition lines allowed us to determine the chromosomal localizations of
      EST-SSR markers and confirm conservation of the linkage group. CONCLUSION: From
      the present study a set of 21 polymorphic EST-SSR markers have been identified to
      be useful for diversity analysis of H. chilense, related wild barleys like H.
      murinum, and for wheat marker-assisted introgression breeding. Across-genera
      transferability of the barley EST-SSR markers has allowed phylogenetic inference
      within the Triticeae complex.

PMID- 18822177
TI  - The influence of the Cyclin D1 870 G>A polymorphism as an endometrial cancer risk
      factor.
AB  - BACKGROUND: Cyclin D1 is integral for the G1 to S phase of the cell cycle as it
      regulates cellular proliferation. A polymorphism in cyclin D1, 870 G>A, causes
      overexpression and supports uncontrollable cellular growth. This polymorphism has
      been associated with an increased risk of developing many cancers, including
      endometrial cancer. METHODS: The 870 G>A polymorphisms (rs605965) in the cyclin
      D1 gene was genotyped in an Australian endometrial cancer case-control population
      including 191 cases and 291 controls using real-time PCR analysis. Genotype
      analysis was performed using chi-squared (chi2) statistics and odds ratios were
      calculated using unconditional logistic regression, adjusting for potential
      endometrial cancer risk factors. RESULTS: Women homozygous for the variant cyclin
      D1 870 AA genotype showed a trend for an increased risk of developing endometrial
      cancer compared to those with the wild-type GG genotype, however this result was
      not statistically significant (OR 1.692 95% CI (0.939-3.049), p = 0.080).
      Moreover, the 870 G>A polymorphism was significantly associated with family
      history of colorectal cancer. Endometrial cancer patients with the homozygous
      variant AA genotype had a higher frequency of family members with colorectal
      cancer in comparison to endometrial cancer patients with the GG and combination
      of GG and GA genotypes (GG versus AA; OR 2.951, 95% CI (1.026-8.491), p = 0.045,
      and GG+GA versus AA; OR 2.265, 95% CI (1.048-4.894), p = 0.038, respectively).
      CONCLUSION: These results suggest that the cyclin D1 870 G>A polymorphism is
      possibly involved in the development of endometrial cancer. A more complex
      relationship was observed between this polymorphism and familial colorectal
      cancer.

PMID- 18822178
TI  - Leaders, leadership and future primary care clinical research.
AB  - BACKGROUND: A strong and self confident primary care workforce can deliver the
      highest quality care and outcomes equitably and cost effectively. To meet the
      increasing demands being made of it, primary care needs its own thriving research
      culture and knowledge base. METHODS: Review of recent developments supporting
      primary care clinical research. RESULTS: Primary care research has benefited from
      a small group of passionate leaders and significant investment in recent decades
      in some countries. Emerging from this has been innovation in research design and
      focus, although less is known of the effect on research output. CONCLUSION:
      Primary care research is now well placed to lead a broad re-vitalisation of
      academic medicine, answering questions of relevance to practitioners, patients,
      communities and Government. Key areas for future primary care research leaders to
      focus on include exposing undergraduates early to primary care research,
      integrating this early exposure with doctoral and postdoctoral research career
      support, further expanding cross disciplinary approaches, and developing useful
      measures of output for future primary care research investment.

PMID- 18822179
TI  - Training of front-line health workers for tuberculosis control: lessons from
      Nigeria and Kyrgyzstan.
AB  - Efficient human resources development is vital for facilitating tuberculosis
      control in developing countries, and appropriate training of front-line staff is
      an important component of this process. Africa and Central Asia are over
      represented in global tuberculosis statistics. Although the African region
      contributes only about 11% of the world population, it accounts for at least 25%
      of annual TB notifications, a proportion that continues to increase due to poor
      case management and the adverse impact of HIV/AIDS. Central Asia's estimated
      current average tuberculosis prevalence rate of 240/100,000 is significantly
      higher than the global average of 217/100,000. With increased resources currently
      becoming available for countries in Africa and Central Asia to improve
      tuberculosis control, it is important to highlight context-specific training
      benchmarks, and propose how human resources deficiencies may be addressed, in
      part, through efficient (re)training of frontline tuberculosis workers. This
      article compares the quality, quantity and distribution of tuberculosis
      physicians, laboratory staff, community health workers and nurses in Nigeria and
      Kyrgyzstan, and highlights implications for (re)training tuberculosis workers in
      developing countries.

PMID- 18822180
TI  - Prevalence of oral pain and barriers to use of emergency oral care facilities
      among adult Tanzanians.
AB  - BACKGROUND: Oral pain has been the major cause of the attendances in the dental
      clinics in Tanzania. Some patients postpone seeing the dentist for as long as two
      to five days. This study determines the prevalence of oral pain and barriers to
      use of emergency oral care in Tanzania. METHODS: Questionnaire data were
      collected from 1,759 adult respondents aged 18 years and above. The study area
      covered six urban and eight rural study clusters, which had been selected using
      the WHO Pathfinder methodology. Chi-square tests and logistic regression analyses
      were performed to identify associations. RESULTS: Forty two percent of the
      respondents had utilized the oral health care facilities sometimes in their
      lifetime. About 59% of the respondents revealed that they had suffered from oral
      pain and/or discomfort within the twelve months that preceded the study, but only
      26.5% of these had sought treatment from oral health care facilities. The reasons
      for not seeking emergency care were: lack of money to pay for treatment (27.9%);
      self medication (17.6%); respondents thinking that pain would disappear with time
      (15.7%); and lack of money to pay for transport to the dental clinic (15.0%).
      Older adults were more likely to report that they had experienced oral pain
      during the last 12 months than the younger adults (OR = 1.57, CI 1.07-1.57, P <
      0.001). Respondents from rural areas were more likely report dental clinics far
      from home (OR = 5.31, CI = 2.09-13.54, P < 0.001); self medication at home (OR =
      3.65, CI = 2.25-5.94, P < 0.001); and being treated by traditional healer (OR =
      5.31, CI = 2.25-12.49, P < 0.001) as reasons for not seeking emergency care from
      the oral health care facilities than their counterparts from urban areas.
      CONCLUSION: Oral pain and discomfort were prevalent among adult Tanzanians. Only
      a quarter of those who experienced oral pain or discomfort sought emergency oral
      care from oral health care facilities. Self medication was used as an alternative
      to using oral care facilities mainly by rural residents. Establishing oral care
      facilities in rural areas is recommended.

PMID- 18822181
TI  - Termites, hemimetabolous diploid white ants?
AB  - Ants and termites are the most abundant animals on earth. Their ecological
      success is attributed to their social life. They live in colonies consisting of
      few reproducing individuals, while the large majority of colony members
      (workers/soldiers) forego reproduction at least temporarilly. Despite their
      apparent resemblance in social organisation, both groups evolved social life
      independently. Termites are basically social cockroaches, while ants evolved from
      predatory wasps. In this review, I will concentrate on termites with an ancestral
      life type, the wood-dwelling termites, to compare them with ants. Their different
      ancestries provided both groups with different life history pre-adaptations for
      social evolution. Like their closest relatives, the woodroaches, wood-dwelling
      termites live inside their food, a piece of wood. Thus, intensive costly food
      provisioning of their young is not necessary, especially as young instars are
      rather independent due to their hemimetabolous development. In contrast, ants are
      progressive food provisioners which have to care intensively for their helpless
      brood. Corresponding to the precocial - altricial analogy, helping by workers is
      selected in ants, while new evidence suggests that wood-dwelling termite workers
      are less engaged in brood care. Rather they seem to stay in the nest because
      there is generally low selection for dispersal. The nest presents a safe haven
      with no local resource competition as long as food is abundant (which is
      generally the case), while founding a new colony is very risky. Despite these
      differences between ants and termites, their common dwelling life style resulted
      in convergent evolution, especially winglessness, that probably accounts for the
      striking similarity between both groups. In ants, all workers are wingless and
      winglessness in sexuals evolved in several taxa as a derived trait. In wood
      dwelling termites, workers are by default wingless as they are immatures. These
      immatures can develop into winged sexuals that disperse and found a new nest or
      into neotenic replacement reproductives that inherit the natal colony. Depending
      on the worker instar from which the latter develop, the neotenic reproductives
      are either apterous or brachypterous, but never winged. I propose that this wing
      polyphenism might present a basis for the evolution of social life in termites.

PMID- 18822182
TI  - Cardiac valvular inflammatory pseudotumor.
AB  - Inflammatory pseudotumors are quasineoplastic lesions that occur in the lungs as
      well as other extrapulmonary sites. The heart is an uncommon site of origin. We
      report a valvular pseudotumor that produced chronic mitral and aortic
      regurgitation in an elderly woman.

PMID- 18822183
TI  - Phosphorylated EGFR and PI3K/Akt signaling kinases are expressed in circulating
      tumor cells of breast cancer patients.
AB  - INTRODUCTION: The phosphoinositide-3 kinase (PI3K)/Akt pathway, operating
      downstream of epidermal growth factor receptor (EGFR) and human epidermal growth
      factor receptor (HER)2, is implicated in cell migration and survival. EGFR and
      HER2 are expressed in circulating tumor cells, but the activation status of
      downstream signaling molecules has not yet been reported. METHODS: To investigate
      expression levels of EGFR, HER2, PI3K, and Akt in circulating tumor cells, we
      used peripheral blood mononuclear cells from 32 cytokeratin-19 mRNA-positive
      patients with early (n = 16) and metastatic (n = 16) breast cancer.Peripheral
      blood mononuclear cell cytospins were double stained with cytokeratin antibody
      along with one of the following: EGFR, phospho-EGFR, HER2, phospho-PI3K, or
      phospho-Akt antibodies. RESULTS: EGFR and HER2 were expressed in circulating
      tumor cells of 38% and 50% patients with early and 44% and 63% patients with
      metastatic disease, respectively. Interestingly, phospho-PI3K and phospho-Akt
      expression levels were similar at 88% (14 out of 16) and 81% (13 out of 16),
      respectively, in circulating tumor cells of patients with early and metastatic
      disease. Phospho-EGFR was observed in circulating tumor cells of two (33%) early
      and six (86%) metastatic EGFR-positive patients. Immunomagnetic separation of
      peripheral blood mononuclear cells, using EpCAM antibody, and subsequent double
      staining experiments of circulating tumor cells showed that EGFR was co-expressed
      with HER2, phospho-Akt and phospho-PI3K kinases, indicating activation of the
      corresponding survival signaling pathway. CONCLUSIONS: Our findings demonstrate
      that circulating tumor cells express receptors and activated signaling kinases of
      the EGFR/HER2/PI3K/Akt pathway, which could be used as targets for their
      effective elimination.

PMID- 18822184
TI  - Hantaviruses and TNF-alpha act synergistically to induce ERK1/2 inactivation in
      Vero E6 cells.
AB  - BACKGROUND: We have previously reported that the apathogenic Tula hantavirus
      induces apoptosis in Vero E6 epithelial cells. To assess the molecular mechanisms
      behind the induced apoptosis we studied the effects of hantavirus infection on
      cellular signaling pathways which promote cell survival. We previously also
      observed that the Tula virus-induced cell death process is augmented by external
      TNF-alpha. Since TNF-alpha is involved in the pathogenesis of hantavirus-caused
      hemorrhagic fever with renal syndrome (HFRS) we investigated its effects on HFRS
      causing hantavirus-infected cells. RESULTS: We studied both apathogenic (Tula and
      Topografov) and pathogenic (Puumala and Seoul) hantaviruses for their ability to
      regulate cellular signaling pathways and observed a direct virus-mediated down
      regulation of external signal-regulated kinases 1 and 2 (ERK1/2) survival pathway
      activity, which was dramatically enhanced by TNF-alpha. The fold of ERK1/2
      inhibition correlated with viral replication efficiencies, which varied
      drastically between the hantaviruses studied. CONCLUSION: We demonstrate that in
      the presence of a cytokine TNF-alpha, which is increased in HFRS patients,
      hantaviruses are capable of inactivating proteins that promote cell survival
      (ERK1/2). These results imply that hantavirus-infected epithelial cell barrier
      functions might be compromised in diseased individuals and could at least
      partially explain the mechanisms of renal dysfunction and the resulting
      proteinuria seen in HFRS patients.

PMID- 18822185
TI  - Domain knowledge moderates the influence of visual saliency in scene recognition.
AB  - Is the sequence of eye-movements made when viewing a picture related to encoding
      the image into memory? The suggestion of a relationship is supported by studies
      that have found that scanpaths are more similar over multiple viewings of a
      stimulus than would be expected by chance. It has also been found that low-level
      visual saliency contributes to the initial formation of these scanpaths, and has
      lead to formation of theories such as the saliency map hypothesis. However,
      bottom-up processes such as these can be overridden by top-down cognitive
      knowledge in the form of domain proficiency. Domain specialists were asked to
      look at a set of photographs of real-world scenes in preparation for a memory
      test. Then they were given a second set of stimuli and were asked to identify the
      picture as old (from the previous set) or new (never seen before). Eye tracking
      analyses (including scanpath comparison using a string editing algorithm)
      revealed that saliency did influence where participants looked and in what
      sequence. However, this was reliably reduced when participants viewed pictures
      from their specialist domain. This effect is shown to be robust in a repeated
      viewing of the stimuli.

PMID- 18822186
TI  - Consistencies in sex differences on the Cognitive Abilities Test across
      countries, grades, test forms, and cohorts.
AB  - BACKGROUND: Strand, Deary, and Smith (2006) reported an analysis of sex
      differences on the Cognitive Abilities Test (CAT) for over 320,000 UK students 11
      12 years old. Although mean differences were small, males were overrepresented at
      the upper and lower extremes of the score distributions on the quantitative and
      non-verbal batteries and at the lower extreme of the verbal battery. AIMS: We
      investigate whether these results were unique to the UK or whether they would be
      seen in other countries, at other grades, cohorts, or forms of the test. SAMPLE:
      The sample consisted of three nationally representative cohorts of US students in
      grades 3 through 11 (total N=318,599) for the 1984, 1992, and 2000
      standardizations of the US version of the CAT. METHODS: We replicated and
      extended the Strand et al. (2006) results by comparing the proportions of males
      and females at each score level across countries (UK vs. US), grades (3-11), and
      cohorts/test forms (Forms 4, 5, and 6 standardized in 1984, 1992, and 2000,
      respectively). RESULTS: The results showed an astonishing consistency in sex
      differences across countries, grades, cohorts, and test forms. CONCLUSIONS:
      Implications for the current debate about sex differences in quantitative
      reasoning abilities are discussed.

PMID- 18822187
TI  - Minimally invasive strategies and options for far-lateral lumbar disc herniation.
AB  - OBJECTIVE: To investigate the surgical procedures, options and surgical
      indications for far-lateral lumbar disc herniation between three different
      minimally invasive procedures. METHODS: From January 2000 to October 2006, 52
      patients with far-lateral lumbar disc herniation (29 males and 23 females, with
      the average age of 41.5 years) were treated with minimally invasive procedures.
      All the patients were assessed by X-ray and CT. Some were given additional
      myeography, discography, Computerized tomography mye-lography (CTM) and MRI
      examination. Yeung Endoscopy Spine System (YESS), METRx and X-tube procedures
      were performed in 25, 13 and 14 cases, respectively. All patients were followed
      up for a mean period of 13.5 months. Clinical outcomes were assessed by visual
      analog score (VAS) and Nakai criteria. RESULTS: The results indicated that the
      three procedures could significantly improve the radiating leg symptoms (P less
      than 0.05). The postoperative overall excellent and good rates of YESS, METRx and
      X-tube procedures were 84.0%, 84.6% and 92.8% respectively, with no statistical
      difference among three groups (P larger than 0.05). The YESS procedure had
      several advantages including shortest operation time, simplest anesthesia and
      least trauma as compared with the other two procedures, especially for simple
      type I far-lateral lumbar disc herniation. METRx procedure was specially suitable
      for simple type II. And the procedure of posterior endoscopic facetectomy,
      posterior lumbar interbody fusion and unilateral pedicle screw instrumentation
      with X-tube was designed for far-lateral disc herniation combined with
      degenerative lumbar instability. CONCLUSION: Minimally invasive strategies and
      options should be determined by different types of far-lateral lumbar disc
      herniation.

PMID- 18822188
TI  - Reimplantation combined with transplantation of transgenic neural stem cells for
      treatment of brachial plexus root avulsion.
AB  - OBJECTIVE: To explore a new method to treat brachial plexus root avulsion
      experimentally by reimplantation combined with transplantation of neural stem
      cells (NSCs) modified by neurotrophin-3 gene (NT-3). METHODS: The total RNA was
      extracted from neonatal rat striatum and the NT-3 cDNA was obtained by reverse
      transcription and amplified by polymerase chain reaction. The NT-3 gene was
      transferred into NSCs via the pLEGFP-C1, an expression plasmid vectors. The
      untransfected NSCs, the pLEGFP-C1 treated NSCs, and the pLEGFP-C1-NT-3 treated
      NSCs were transplanted into corresponding spinal cord segment with brachial
      plexus root avulsion. The survival, differentiation, and migration of the
      transplanted cells were determined under confocal laser scanning microscope or by
      immunohistochemistry method. The nerve regeneration was evaluated by gross
      observation, electrophysiological examination and reverse horseradish peroxidase
      tracing. RESULTS: The NT-3 gene was successfully amplified and transferred into
      neural stem cells via the plasmid vectors. The transplanted cells survived,
      differentiated, and migrated and NT-3 was expressed within the spinal cord. The
      animals regained some muscle strength which was less than 3-degree muscular
      strength according to the British Medical Research Council (BMRC) evaluating
      system. The results of electrophysiological examination and reverse horseradish
      peroxidase tracing were superior in the pLEGFP-C1-NT-3 group to the NSCs
      untransfected group or the pLEGFP-C1 group. CONCLUSION: Transplantation of NSCs
      modified by NT-3 gene combined with reimplantation is a relatively effective way
      to treat brachial plexus root avulsion experimentally. It still need further
      study to improve the results.

PMID- 18822189
TI  - Curative effect and histocompatibility evaluation of reconstruction of traumatic
      defect of rabbit urethra using extracellular matrix.
AB  - OBJECTIVE: To investigate the curative effect and histocompatibility of
      reconstruction of traumatic urethral defect of rabbit using urethral
      extracellular matrix (ECM). METHODS: Urethral ECM was obtained by excision of the
      urethra in 20 donor rabbits. In experimental group, 20 rabbits were resected a
      1.0 cm-1.5 cm segment of the urethra and artificially made a model of traumatic
      urethral defect, then reconstructed by the urethral extracellular matrix of the
      same length. The rabbit immunity response was assessed by lymphocyte
      transformation test and serum TNF-alpha level. The reconstructed urethral
      segments were stained with hematoxylin-eosin and Van Gieson stain and observed by
      histological examination postoperatively. The urethrography, urethroscopy and
      urodynamic examinations were performed. RESULTS: There was no significant
      difference in stimulative index of lymphocyte transformation between ECM group
      and control group. The serum TNF-alpha levels of ECM group slightly rose, but the
      increase was not significant as compared with control group. On postoperative day
      10, epithelial cell had migrated from each side and small vessels were found in
      the extracellular matrix. In the 3rd week, several layers of urothelium covered
      the whole surface of the matrix tube. In the 6th week, the disorganized
      arrangements of smooth muscle fibers were firstly observed by Van Gieson
      staining. In the 24th week, the smooth muscle cells increased and the matrix tube
      appeared fairly similar to normal urethral wall components. The urethroscopy and
      urodynamic evaluation revealed that the surface of reconstructed urethra was
      smooth and emiction was unobstructed. CONCLUSION: The urethral extracellular
      matrix might be an ideal and safe biomaterial for the reconstruction of urethral
      traumatic defect.

PMID- 18822190
TI  - An anatomic study of vascularized fibular grafts.
AB  - OBJECTIVE: To study the applied anatomy of the vascular and muscular innervations
      related to vascularized fibular grafts. METHODS: Thirty-four cadaveric lower
      extremities were dissected for this study. The observations included fibular
      length, fibular nutrient artery, arcuate arteries, and innervation of fibular
      muscles. The fibulas were averagely divided into four segments and the locations
      of relevant vessels and nerves were ascertained. RESULTS: All specimens had 1
      fibular nutrient artery and 4-9 arcuate arteries except 1 specimen which had only
      1 arcuate artery. The fibular nutrient artery and the first three arcuate
      arteries were constantly located between the distal half of the 1/4 segment and
      2/4 segment of the fibula. The muscular branch of the superficial peroneal nerve
      passed through the surface of the periosteum in the 2/4 segment of the fibula.
      CONCLUSIONS: The most proximal osteotomy point locates at the midpoint of the 1/4
      segment by which it ensure the maximal potential for preserving the nutrient
      vessels. The muscular branch of the superficial peroneal nerve is fragile to
      injury at the 2/4 segment of the fibula.

PMID- 18822191
TI  - Damage control orthopaedics in 53 cases of severe polytrauma who have mainly
      sustained orthopaedic trauma.
AB  - OBJECTIVE: To discuss damage control orthopaedics in 53 cases of severe
      polytrauma who have mainly sustained orthopaedic trauma. METHODS: The data of 53
      cases of severe polytrauma who had mainly sustained orthopaedic trauma were
      retrospectively analyzed. And the methods and timing of damage control
      orthopaedics were discussed in this study. RESULTS: We succeeded in rescuing the
      lives of all the 53 patients, and 38 patients returned to their former work.
      CONCLUSIONS: Injury Severity Score (ISS(90)) should be 17 in severe polytrauma
      patients, but in severe polytrauma patients who have mainly sustained orthopaedic
      trauma, the ISS(90) of bone and joint injuries should be 16. We recommend that
      primary minimally-invasive external fracture stabilization should be made for
      extremities and pelvis in these patients to avoid additional surgical trauma and
      that definitive secondary fracture care should be performed after medical
      stabilization for these patients in intensive care unit (ICU).

PMID- 18822192
TI  - Arthroscopically assisted treatment for Schatzker type I-V tibial plateau
      fractures.
AB  - OBJECTIVE: To report the clinical outcome of arthroscopically assisted treatment
      for tibial plateau fractures. METHODS: A total of 39 patients with tibial plateau
      fractures were treated by arthroscopic fixation from February 2002 to December
      2005, including 11 patients with bony avulsion of the anterior cruciate ligament
      and 19 with meniscal injury. There were 4 cases of type I fracture, 12 type II, 9
      type III, 12 type IV and 2 type V according to Schatzker criteria. Firstly, the
      combined injuries were treated. Then the plateau fractures with the displacement
      over 3 mm or more were reduced and fixed. Finally, the internal fixation was
      observed by X-ray equipment. Postoperative management was early motion and
      delayed weight bearing. RESULTS: All the fractures healed in 3 or 4 months. All
      patients were followed up for 1 to 5 years after operation. No case had severe
      complications, such as poor wound healing, infection, osteofascial compartment
      syndrome and osteoarthritis. According to the Rasmussen scoring system, 36 cases
      obtained excellent or good results and the other 3 cases had moderate clinical
      results. The average score was 26+/-3. CONCLUSIONS: As an adjuvant treatment of
      intraarticular fractures such as tibial plateau fracture, arthroscopy has many
      advantages. It can treat associated intraarticular soft tissue components,
      visualize the chondral surface reduction, lavage the hematoma and smaller loose
      fragments, decrease soft tissue dissection, reduce the risk of scarring and
      promote rapid recovery.

PMID- 18822193
TI  - Influence of sodium hyaluronate on iNOS expression in synovium and NO content in
      synovial fluid of rabbits with traumatic osteoarthritis.
AB  - OBJECTIVE: To observe the influence of intra-articular injection of sodium
      hyaluronate (SH) on the expression of inducible nitric oxide synthase (iNOS) in
      the synovium and nitric oxide (NO) content in synovial fluid of rabbits with
      traumatic osteoarthritis (OA). METHODS: Sixteen white rabbits underwent
      unilateral anterior cruciate ligament transection and were randomly divided into
      2 groups 5 weeks after the operation. Rabbits in the experimental group received
      intra-articular injection of 0.3 ml of 1% SH, once a week for 5 weeks. Animals in
      the control group were treated under the same conditions using physiological
      saline. All the animals were sacrificed at the 10th week after surgery. The mRNA
      expression of iNOS in the synovium was analyzed using reverse transcription
      polymerase chain reaction. The content of NO in the synovial fluid was assayed.
      RESULTS: The level of iNOS expression of the synovium in the experimental group
      was lower than that in control group (0.47+/-0.09 vs. 0.65+/-0.12, t equal to
      3.45, P less than 0.01). Compared with control group, the content of NO decreased
      significantly in synovial fluid of SH injection group (134.11 micromolar/L +/-
      12.47 micromolar/L vs. 152.17 micromolar/L +/- 15.69 micromolar/L, t equal to
      2.55, P less than 0.05). CONCLUSIONS: SH significantly decreases the content of
      NO in the synovial fluid of rabbits with traumatic OA. SH may exert the effect on
      synovial fluid NO level as a result of the suppression of iNOS expression in the
      synovium. It may be one of the mechanisms of the therapeutic effect of SH on
      early traumatic OA.

PMID- 18822194
TI  - Ultrasonography for non-displaced and mini-displaced humeral lateral condyle
      fractures in children.
AB  - OBJECTIVE: To evaluate the value of ultrasonography in non-displaced and mini
      displaced humeral lateral condyle fractures in children. METHODS: Nine children
      aged 2-9 years with non-displaced or mini-displaced humeral lateral condyle
      fractures were examined by high-resolution ultrasonography. The fracture line
      through the joint surface was visualized by ultrasonography in 6 case, in which
      closed reduction and percutaneous pinning was performed on 3 patients and other 3
      patients did not receive the treatment because of patients'or their
      parents'refusal. In the remaining 3 children, ultrasonography did not reveal the
      cartilaginous trochle involvement at the joint surface and conservative treatment
      was adopted. RESULTS: The average follow-up period was 8 months. The sonographic
      findings were confirmed by magnetic resonance imaging in one child who received
      conservative treatment and another child who received percutaneous pinning. The
      elbow function and fracture healing were good in cases received closed reduction
      and percutaneous pinning. Among the three cases who refused to receive closed
      reduction and internal fixation, re-displacement occurred in 1 case and delayed
      union in 1 case. All three cases receiving conservative treatment had good
      results both in elbow function and fracture healing. CONCLUSION: High-resolution
      ultrasonography enable to reveal non-displaced and mini-displaced humeral lateral
      condyle fractures as well as to ascertain whether the cartilaginous trochlea
      humeri was involved. For these cases, arthrography or magnetic resonance imaging
      is unnecessary.

PMID- 18822195
TI  - Clinical observation of particulate cancellous bone impaction grafting in
      combination with total hip arthroplasty for acetabular reconstruction.
AB  - OBJECTIVE: To investigate the effect of particulate cancellous bone impaction
      grafting in combination with total hip arthroplasty (THA) for acetabular
      reconstruction in patients with posttraumatic arthritis and bone loss after
      acetabular fractures. METHODS: Totally 15 consecutive cases with unilateral
      acetabular fracture were treated with bone impaction grafting in combination with
      THA in our department. There were 10 males and 5 females with mean age of 48.2
      years (ranging from 36 to 73 years). Eight cases had the fracture at left hips, 7
      at right hips. The average age at injury was 28 years (ranging from 18 to 68
      years). The mean follow-up period was 4.3 years (ranging from 2 to 7 years).
      RESULTS: Compared with mean 42 points (ranging from 10 to 62) of the preoperative
      Harris score, the survival cases at the final follow-up had mean 84 points
      (ranging from 58 to 98). One patient had mild pain in the hip. No revision of the
      acetabular or femoral component was undertaken during the follow-up. Normal
      rotational centre of most hips was recovered except 2 cases in which it was 0.8
      mm higher than that in opposite side. All of them had a stable radiographic
      appearance. Progressive radiolucent lines were observed in I, III zones in 2
      cases. One patient had a nonprogressive radiolucent line in zone III. The cup
      prosthesis was obviously displaced (6 mm) in one patient, but had not been
      revised. CONCLUSION: Particulate cancellous bone impaction grafting in
      combination with THA as a biological solution is an attractive procedure for
      acetabular reconstruction in patients with posttraumatic arthritis and bone loss
      after acetabular fracture, which can not only restore acetabular bone stock but
      also repair normal hip anatomy and its function.

PMID- 18822196
TI  - Control of demyelination for recovery of spinal cord injury.
AB  - Since loss of oligodendrocytes and consequent demyelination of spared axons
      severely impair the functional recovery of injured spinal cord, it is reasonably
      expected that the reduction of oligodendroglial death and enhanced remyelination
      of demyelinated axons will have a therapeutic potential to treat spinal cord
      injury. Amelioration of axonal myelination in the injured spinal cord is valuable
      for recovery of the neural function of incompletely injured patients. Here, this
      article presents an overview about the pathophysiology and mechanism of axonal
      demyelination in spinal cord injury and discusses its therapeutic significance in
      the treatment of spinal cord injury. Moreover, it further introduces the recent
      strategies to improve the axonal myeliantion to facilitate functional recovery of
      spinal cord injury.

PMID- 18822197
TI  - Hypogastric artery autograft treating hemorrhage with infection of external iliac
      artery secondary to renal transplantation.
AB  - Massive hemorrhage from infected anastomosed site between the graft artery and
      the external iliac artery is one of the most serious complications of renal
      transplantation. Clinically, it is a rare but fatal occasion. We reported here
      one case of hemorrhage with infection in the iliac artery anastomosed site
      treated successfully with hypogastric artery autograft interposition in March
      2003.

PMID- 18822198
TI  - Leakage of cerebrospinal fluid and secondary intracranial infection induced by
      Cloward technique of cervical discectomy and fusion: presentation and treatment.
AB  - Cloward technique of cervical discectomy and fusion is a long and complex
      surgical procedure and instrumentation, by which complicated infection is rare in
      an era of routine prophylactic antimicrobial agent, especially in procedures by
      anterior approach. A study in the journal of Spine suggested that the incidence
      of unintentional laceration of the dura mater during spinal surgery might be as
      high as 14%.1 A majority of them are repaired intraoperatively and/or present as
      a spontaneous process of healing. Therefore, leakage of cerebrospinal fluid (CSF)
      and secondary intracranial infection induced by incidental durotomy are rare.
      Levi et al.2 reviewed spinal instrumentation procedures in 452 cases at a single
      institution, finding that 17 patients got infections in the operative areas.
      Infection occurred after posterior spinal instrumentation procedures (7.2%) and
      no infection was found after anterior instrumentation procedures regardless of
      the vertebral levels. Likewise, Aydinli et al.3 reported that 8 patients were
      complicated by acute infection out of 174 patients undergoing instrumented spinal
      surgery, including no anterior procedures. To our knowledge, we are the first to
      report a complete clinical course concerning CSF leakage and secondary
      intracranial infection induced by Cloward technique of cervical discectomy and
      fusion.

PMID- 18822199
TI  - Prefabricated flap to repair heel defect of child.
AB  - The coverage of large soft tissue defects in heel is a problem for surgical
      reconstruction. Various reconstructive materials are available depending on the
      location, size and depth of heel defect, but unique function of heel skin cannot
      be restored easily by means of reconstruction. We used prefabricated flap of the
      foot heel to cover heel defect in a child and obtained satisfactory clinical
      results.

PMID- 18822200
TI  - [Short-term results of telbivudine versus entecavir treatments in HBeAg-positive
      chronic hepatitis B patients in China].
AB  - OBJECTIVE: To evaluate the efficacy and safety of telbivudine (LDT) versus
      entecavir treatments in hepatitis B e antigen (HBeAg)-positive chronic hepatitis
      B (CHB) patients. METHODS: Eighty HBeAg-positive compensated CHB patients with
      HBV DNA more than 6 log10 copies/ml and serum ALT 2 x ULN were divided into two
      groups: a telbivudine treatment group, and a entecavir treatment group. HBV DNA,
      ALT and HBeAg were surveyed at baseline and at 12 and 24 weeks. The efficacy and
      safety of the two nucleoside analogues were assessed at 12 and 24 weeks. RESULTS:
      Undetectable serum HBV DNA levels of the telbivudine group (50% and 80%) were
      similar to those of the entecavir B group (50% and 70%) according to the
      polymerase-chain-reaction assay at week 12 and 24. There were no significant
      differences in the normalization of alanine aminotransferase levels between the
      two groups at week 12 and 24 (52.5% vs 60.0%, 77.5% vs 75.0%). The mean
      reductions in serum HBV DNA from the baseline levels at week 12 and 24 were
      similar between the two groups [5.27 vs.5.36, 6.49 vs.6.18 log (on a base-10
      scale) copies per milliliter]. More patients in the telbivudine group had HBeAg
      seroconversion at week 12 than those in the entecavir group (20.0% vs 5.0%, P =
      0.043); however, there was no significant difference between the two groups at
      week 24 (27.5% vs 17.5%). No adverse reactions were found in either group.
      CONCLUSION: There was no significant difference in HBV DNA undetectable rates and
      the ALT normalization rates between the two groups in a short-term therapy (24
      weeks), but the telbivudine group had a higher rate in HBeAg seroconversion than
      that in the entecavir group at week 12.

PMID- 18822201
TI  - [The relationship between alpha-IFN anti-virus treatment and HLA-DRB1*11 gene
      mononucleotide polymorphism].
AB  - OBJECTIVE: To investigate the relationship between the distribution of
      mononucleotide polymorphism of five regulation regions of alpha-IFN among HLA
      DRB1*11 gene episodes and the therapeutic effects of alpha-IFN treatment in
      chronic hepatitis B patients. METHODS: One hundred seven chronic hepatitis
      patients from Nanjing Second Hospital who were treated by alpha-IFN for 12 months
      and then followed at least six months without the treatment were randomly
      selected for this regressive analysis. They were grouped into a continuous
      responsive group and a non-continuous responsive group. Hepatitis B virus X
      interacting protein gene locus was searched in NCBI. Single nucleotide
      polymorphism (SNP) gene locus was detected based on a pooling sequencing method.
      Primer and TaqMan-MGB probes referring to different mononucleotide loci were
      designed respectively to detect SNP in five regulation regions of alpha-IFN. Then
      gene sequencing differences between the two groups were analyzed. RESULTS: Among
      the 107 cases there were 30 cases (28.0%) in the continuous responsive group and
      77 cases (71.9%) in the non-continuous responsive group. CT occupation rate in
      five regulation regions of IFN reached 18.0% in the continuous responsive group
      and 23.8% in the non-continuous responsive group. AG occupation rate reached
      10.8% in the former group and 15.8% in the latter group. The differences in CT
      and AG between the two groups were significant. CONCLUSIONS: The distribution of
      mononucleotide polymorphism of five regulation regions of alpha-IFN among HLA
      DRB1*11 gene episodes affects the IFN anti-virus treatment. Detecting the gene
      distribution of mononucleotide in five regulation regions of alpha-IFN helps in
      predicting the therapeutic effects of alpha-IFN.

PMID- 18822202
TI  - [Dynamic expression of PD-1 in HBV-specific cytotoxic T lymphocytes correlates
      with memory T-cell development in acute hepatitis B patients].
AB  - OBJECTIVES: Programmed death-1 (PD-1) up-regulation impairs virus-specific CD8+ T
      cell responses during chronic viral infection. Whether PD-1 expression influences
      the virus-specific CD8+ T cells in humans with acute viral infection remains
      largely undefined. This study aims to characterize the PD-1 expression during
      acute hepatitis B (AHB), and further addresses the association between the PD-1
      dynamics and memory T-cell formation during acute HBV infection. METHODS:
      Peripheral HBV-specific CD8+ T cells from 11 HLA-A2-positive AHB patients were
      longitudinally quantitatively analyzed, and PD-1, memory markers CCR7, CD45RA and
      CD127 and activation marker CD38 on HBV-specific CD8+ T cells were measured using
      flow cytometric assay. Serum ALT, HBsAg, HBsAb and HBV-DNA levels were evaluated
      for each subject. RESULTS: All 11 AHB patients examined had multiple pentamer
      positive CD8+ T-cell responses in their early phase of HBV infection.
      Specifically, their PD-1 on pentamer-positive CD8+ T-cells was significantly up
      regulated at the onset of their disease. Following their disease resolution, the
      dynamic decrease in PD-1 expression was found to correlate with the phenotypic
      development of memory CD8+ T cells, indicated by the increases in CCR7, CD45RA
      and CD127 and decrease in CD38. CONCLUSION: PD-1-mediated negative signaling may
      be closely associated with memory T-cell formation during acute self-limited
      hepatitis B.

PMID- 18822203
TI  - [An analysis of CD3+CD56+ lymphocytes and their subsets in the peripheral blood
      of patients with chronic hepatitis B].
AB  - OBJECTIVES: To investigate CD3+CD56+ lymphocytes and their subsets in the
      peripheral blood of chronic hepatitis B patients and to explore the relationship
      between these cells and the pathogenesis of their diseases. METHODS: Blood
      samples from 53 chronic hepatitis B patients, 17 from HBV asymptomatic carriers
      (ASC) and 19 from healthy controls (HC) were collected. CD3+CD56+ lymphocytes
      were detected by flow cytometry (FCM), then the CD3+CD56+ lymphocytes were
      gathered to analyze their expressions of CD4, CD8, TCR Valpha24, TCRalpha/beta
      and TCRgamma/delta. RESULTS: The number of CD3+CD56+ lymphocytes of chronic
      hepatitis B patients (7.4+/-4.6%) was more than those of ASC (4.5%+/-3.5%) and
      healthy controls (4.4%+/-3.7%). The expressions of TCR Valpha24 on CD3+CD56+
      lymphocytes showed no significant differences among the three groups, but the
      expression of TCR Valpha24 on CD3-CD56+ lymphocytes of ASC ( 2.8%+/-1.4% ) was
      much more than that of the HC (1.7%+/-1.0%). For the subsets analysis, the CD8
      and TCRalpha/beta subsets of CD3+CD56+ lymphocytes of chronic hepatitis B
      (61.9%+/-16.8% and 68.1%+/-16.9%) were significantly higher than those of the HC
      (49.2%+/-15.6% and 56.4%+/-17.9%), while the TCRgamma/delta subsets of chronic
      hepatitis B and ASC (29.6%+/-15.4% and 30.5%+/-14.8%) were decreased
      significantly than those of the HC (41.4%+/-19.4%). On the other hand, the CD8
      and TCRalpha/beta subsets of CD3+CD56+ lymphocytes of severe chronic hepatitis B
      (69.0%+/-14.0% and 76.1%+/-12.9%) and CD8 subsets of moderate chronic hepatitis B
      patients (66.4%+/-14.9%) were significantly higher than those of the mild chronic
      hepatitis B patients (51.4%+/-16.2% and 62.1%+/-14.6%). CONCLUSION: The
      pathogenesis of chronic hepatitis B may positively relate to the high expression
      of CD8 on the CD3+CD56+ lymphocytes.

PMID- 18822204
TI  - [Effects of trichostatin A on the interaction between HBx and histone deacetylase
      protein 1].
AB  - OBJECTIVES: To study the effects of trichostatin A (TSA) on protein-protein
      interaction between HBx and histone deacetylase protein 1 (HDAC1). METHODS: Both
      HBx and HDAC1 expressing vectors were constructed by the method of routine
      molecular cloning. The expression of HBx and HDAC1 were observed by Western blot
      assay. The protein-protein interaction was tested between HBx and HDAC1 by GST
      pull-down in vitro as well as co-immunoprecipitation in vivo. RESULTS: Both HBx
      and HDAC1 expressing vectors were successfully constructed. Protein-protein
      interaction between HBx and HDAC1 existed both in vitro and in vivo. TSA, an
      inhibitor of HDAC1, had no effect on the interaction between HBx and HDAC1.
      CONCLUSIONS: HBx interacts with HDAC1 in vivo and in vitro in a non- TSA
      dependent way.

PMID- 18822205
TI  - [The functions of liver natural killer cells in murine fulminant hepatitis
      induced by murine hepatitis virus strain 3].
AB  - OBJECTIVES: To investigate the role of liver natural killer cells (NK cells) in
      murine hepatitis virus strain 3 (MHV-3) induced murine fulminant hepatitis.
      METHOD: Balb/cJ mice (6-8 weeks, female) were intraperitoneally injected with 100
      PFU MHV-3. The numbers of NK cells in their livers, spleens, blood and bone
      marrow and the expression of CD69 on liver NK cells at 0, 24, 48 and 70 h after
      MHV-3 infection were analyzed by flow cytometry. The cytotoxic activity of liver
      NK cells was detected by a non-radioactive cytotoxicity assay. The levels of IFN
      gamma produced by hepatic NK cells were detected by intracellular cytokine
      staining. RESULT: Following MHV-3 infection, the proportion of liver NK cells in
      the mice increased remarkably and reached the peak (43.9%+/-2.3%) at 48 h, then
      kept a high proportion until the mice were sacrificed. The proportion of NK cells
      in the peripheral blood also significantly increased and reached the peak
      (18.0%+/-5.4%) at 48 h. However, there were few NK cells in the peripheral blood
      at 70 h after infection; the ratio was only 1.3%+/-0.6%. In the spleens and bone
      marrow, the proportions of NK cells were both significantly decreased from 0 h to
      48 h and then slightly increased. The expression of CD69 on liver NK cells was
      highly up-regulated after the infection and the cytotoxic activity of hepatic NK
      cells at 48 h was also significantly enhanced. In addition, an increase in IFN
      gamma production by hepatic NK cells was observed at 48 h. CONCLUSION: After MHV
      3 infection, NK cells were recruited to the liver quickly, probably from the
      spleen and bone marrow. Recruited NK cells remarkably express CD69, enhance
      cytotoxic activity and IFN gamma production, which correlate with the disease
      severity of fulminant viral hepatitis. Our results suggest that liver NK cells
      may play a pivotal role in the pathogenesis of fulminant viral hepatitis.

PMID- 18822206
TI  - [Effects and the mechanism of HGF on the apoptosis of rat primary cultured
      hepatic stellate cells treated with platelet-derived growth factor].
AB  - OBJECTIVE: To investigate the inhibitory effect of hepatocyte growth factor (HGF)
      on the apoptosis of rat primary cultured hepatic stellate cells treated with
      platelet-derived growth factor BB (PDGF-BB). METHODS: Hepatic stellate cells were
      cultured and treated with PDGF-BB+HGF, HGF or nothing (controls). Apoptosis of
      these hepatic stellate cells was evaluated by AO/EB staining, TUNEL and flow
      cytometry. Expression level of P65 was observed with immunocytochemical staining;
      DNA-protein binding complex of NF-kappa B was detected by electrophoretic
      mobility shift assay. RESULTS: The cell apoptosis rate of the control group was
      lower than that of the PDGF-BB+HGF group. The apoptosis rate of the PDGF-BB+HGF
      group was lower than that of the HGF treated group; the expression of P65 was
      lower in the PDGF-BB+HGF group and HGF treated group compared to the normal
      control group; DNA-protein binding activity of NF-kappa B was respectively
      attenuated in the normal control group, PDGF-BB+HGF treated group and HGF treated
      group (P less than 0.05). CONCLUSION: HGF can induce HSC apoptosis. Its possible
      mechanism may involve inhibiting DNA-protein binding activity of NF-kappa B and
      down-regulating the expression level of P65.

PMID- 18822207
TI  - [Dynamic expression and quantitative analysis of hepatic nuclear factor-kappa B
      and its gene during the development of hepatocellular carcinoma].
AB  - OBJECTIVE: To investigate the kinetic expression and alteration of nuclear
      transcription factor-kappa B (NF-kappaB) and its gene in hepatocellular carcinoma
      (HCC) development. METHODS: A hepatoma model was established with N-(2-fluorenyl)
      acetamide (2-FAA) using male SD rats. Morphological changes and dynamic
      alterations of NF-kappaB and NF-kappaB mRNA of the rat livers at different stages
      of HCC development were observed by pathological examinations. The liver
      specimens from HCC patients were collected by self-control method. The expression
      of NF-kappaB was quantitatively analyzed by ELISA. RESULTS: Hepatocytes showed
      vacuole-like denaturation, atypical hyperplasia, and transformation into highly
      differentiated cancerous hepatocytes with increasing tendencies of liver NF
      kappaB and NF-kappaB mRNA expressions. The NF-kappaB positive material was
      granule-like and stained brown, with dot-nest-like staining localized in the
      nuclei and cytoplasm of HCC cells, but only in the cytoplasm of the cells of park
      cancer tissues. Its expression in HCC cells was stronger than that in their
      surrounding tissues (chi2 = 13.1, P less than 0.01). No positive relationship was
      found between NF-kappaB expression and histological grades, the number of tumors,
      or size of the tumors. CONCLUSION: The expression of NF-kappaB and its gene are
      associated with the development of HCC. To inhibit the expression may be useful
      to HCC therapy.

PMID- 18822208
TI  - [Effects of over-expressed Smac gene coupling with cisplatin on proliferation and
      apoptosis of hepatocarcinoma cells].
AB  - OBJECTIVE: To investigate the effects of over-expressed Smac gene combined with
      cisplatin (CDDP) on proliferation and apoptosis of hepatic carcinoma cells.
      METHODS: The recombinant plasmid pcDNA3.1+-hSmac was introduced into the human
      hepatic carcinoma SMMC-7721 cells using a liposome-mediated method. The
      expression of Smac protein was detected by Western blot and flow cytometry. The
      cells were treated with three different doses of CDDP, 5, 15 and 25microg/ml, for
      24 hours after the transfection. MTT colorimetry was used to detect the cellular
      growth-inhibitory effects; acridine orange-ethidium bromide fluorescent staining
      (AO/EB) and flow cytometry with annexin V-PI double staining METHODS: were used
      to detect the changes of cell apoptosis. RESULTS: Western blot and flow cytometry
      results demonstrated that the Smac protein level in SMMC-7721 cells was
      significantly increased after the transfection (P less than 0.01). Compared with
      that of the control group, the over-expressed Smac gene inhibited the cell growth
      and induced cell apoptosis (P less than 0.01). After being treated with CDDP, the
      inhibitory rates were increased significantly with increasing concentrations of
      CDDP compared with that of the control group, and the inhibitory rate of the CDDP
      treated plus Smac group was significantly higher than that of the CDDP-treated
      group (P less than 0.01). The results detected by AO/EB and flow cytometry
      demonstrated that the apoptotic rates of CDDP-treated plus Smac group were higher
      than those of the CDDP-treated group (P less than 0.01). The results demonstrated
      that the Smac over-expression enhanced the effects of cell growth inhibition and
      apoptotic promotion induced by CDDP. CONCLUSION: The pro-apoptotic Smac gene
      could be over-expressed in hepatocarcinoma SMMC-7721 cells and inhibit cell
      growth and induce apoptosis. Moreover the over-expressed Smac could enhance the
      chemotherapeutic sensitivity of SMMC-7721 to cisplatin. This experimental work
      may help in further study on the regulatory mechanism of Smac in apoptosis and
      improve the chemotherapeutic effect on hepatoma.

PMID- 18822209
TI  - [Inhibition of HSP70-2 expression by RNA interference induces apoptosis of human
      hepatocellular carcinoma cells].
AB  - OBJECTIVES: To determine the effect of short hairpin RNA targeting HSP70-2 on the
      growth and apoptosis of hepatocellular carcinoma (HCC) cells, and to elucidate
      its possible mechanisms in mitochondria apoptotic pathway. METHODS: Western blot
      and immunocytochemistry were used to determine the expression of HSP70-2 in HCC
      cells and normal hepatocytes. HepG2 and Huh-7 cells were cultured and transfected
      with HSP70-2 shRNA1 and shRNA2. Cell proliferation was examined by MTT. Cell
      apoptosis and mitochondria membrane potential were determined by flow cytometry.
      Western blot was used to analyze the expressions of apoptosis related proteins
      including Bax, Bcl-2, PARP, caspase-9 and caspase-3. RESULTS: HSP70-2 was
      expressed at high levels in hepatocellular carcinoma (HCC) cells (SNU-449, HepG2,
      Huh-7, Hep3B) whereas there were very low levels in normal hepatocytes (L02).
      Using DNA vector-based RNA interference, we found that knockdown of HSP70-2
      inhibited the growth of HCC cells through induction of mitochondria-dependent
      apoptosis. The mitochondria-dependent apoptosis induced by HSP70-2 knockdown was
      indicated by cytochrome c release from mitochondria, activation of caspase-9 and
      caspase-3, and loss of mitochondrial potential. Furthermore, knockdown of HSP70-2
      resulted in up-regulation of the pro-apoptotic factor Bax and down-regulation of
      the pro-survival factor Bcl-2. CONCLUSIONS: Our results indicated that HSP70-2
      down-regulation induces apoptosis of HCC cells through the mitochondrial
      apoptotic pathway, highlighting the importance of HSP70-2 in survival of HCC
      cells and maintenance of liver function.

PMID- 18822210
TI  - [Effect of KLF6 and its splice variant KLF6V on proliferation and differentiation
      of human hepatocellular carcinoma HepG2 cells].
AB  - OBJECTIVE: To investigate the roles of Kruppel-like factor 6 (KLF6) and its
      splice variant KLF6V on suppressing growth and inducing differentiation of human
      hepatocellular carcinoma hepG2 cells. METHOD: KLF6V cDNA was amplificated by RT
      PCR from human hepatocellular carcinoma (HCC) tissue and then sequenced. The
      recombinant vectors expressing KLF6 variant (KLF6V) were constructed using
      molecular clone technology based on established plasmid pcDNA3.1A(-)/wtKLF6.
      KLF6V or KLF6-transfected HepG2 cells were established after being screened with
      G418. Growth activity of HepG2/KLF6 or HepG2/KLF6V cells was detected by in vitro
      MTT assay. Expression of p21WAF1 or cyclin D1 protein was detected by Western
      blot, and expressions of AFP or ALB protein were measured by radioimmunoassay.
      RESULTS: A novel alternatively spliced transcript of the human KLF6 gene was
      found and its sequencing revealed that the variant form of KLF6 lacked 126nt and
      its encoded protein products had a deletion of 42 aa near the COOH-terminal amino
      acid in comparison with full-length KLF6. Although KLF6 alternative splicing was
      present in both normal and cancerous tissues, expression of the KLF6 splice
      variants seemed to be up-regulated in HCCs tissues. The isoform of KLF6 proteins
      antagonized the ability of wild-type KLF6 to up-regulate p21 expression or down
      regulate cyclin D1 expression and suppress HepG2 cell proliferation. KLF6 gene
      increased albumin production and decreased alpha fetoprotein production of the
      cells. CONCLUSION: The isoform of KLF6 protein, present in HCC tissue,
      antagonizes the ability of wild-type KLF6 to suppress cell proliferation and
      induce cellular differentiation.

PMID- 18822211
TI  - [Experimental study of transplanting human mesenchymal stem cells via portal vein
      to treat acute liver injury of mice induced with acetaminophen].
AB  - OBJECTIVE: To evaluate the effects of human mesenchymal stem cells (hMSCs)
      transplantation via portal vein to treat acute liver injury in mice induced with
      acetaminophen. METHODS: A model of acute liver injury was established by
      acetaminophen gavage with a dose of 500 mg/kg. Twenty severe combined immune
      deficient mice (SCID mice) were randomly divided into 2 groups; one with hMSCs
      transplantation via their portal veins, the other group served as controls and
      only saline was infused into their veins. Liver function tests, fluorescein
      staining and reticular fiber staining of liver histological preparations and
      fluorescence- and light-microscopy were applied to observe the biochemical and
      pathological changes in the mice before and after the transplantation of hMSCs.
      RESULTS: Liver function of the hMSCs group was significantly better than that of
      the controls (P less than 0.05). Fluorescence microscopy revealed that the hMSCs
      appeared in the areas of the periportal veins at first and then extended to the
      central vein areas; the reticular fiber staining indicated that hMSCs could
      repair the architecture of the hepatic acini. No prominent fibrosis and
      pseudolobules were found. CONCLUSIONS: hMSCs transplantation via portal vein to
      SCID mice with acute liver injury induced by acetaminophen can improve their
      liver function effectively; hMSCs growth in their livers and acinus
      reconstruction can be affected. We think it is a good method to treat acute liver
      injury.

PMID- 18822212
TI  - [An experimental study of plasma-perfusion with a novel aminated chitosan on
      liver failure in a canine model].
AB  - OBJECTIVE: To study the efficacy and safety of plasma-perfusion with a novel
      aminated chitosan on liver failure in a canine model. METHODS: A canine model of
      liver failure was established. Plasma-perfusion with a novel aminated chitosan
      was performed on those dogs. Blood pressure and body temperature during plasma
      perfusion were monitored. Total plasma bilirubin, direct bilirubin and indirect
      bilirubin at the entrance and exit of a column before and after plasma-perfusion
      and at the time of 15, 30, 60, and 120 min during plasma-perfusion were examined.
      Blood alanine aminotransferase, aspartate aminotransferase, ammonia, plasma
      prothrombin time, electrolytes and other blood parameters were examined before
      and after the plasma-perfusion. RESULTS: After the plasma-perfusion, total
      bilirubin decreased from 177.4+/-18.1 to 46.1+/-3.7 (P less than 0.05), direct
      bilirubin decreased from 124.2+/-10.3 to 30.5+/-1.7 (P less than 0.05), indirect
      bilirubin decreased from 53.2+/-2.8 to 15.6+/-2.0 (P less than 0.05). Compared at
      the entrance of the column, there were significant decreases in the levels of
      total bilirubin, direct bilirubin and indirect bilirubin of plasma at the exit of
      the column at the times of 15 and 30 min during plasma-perfusion (P less than
      0.05); there were no further significant decreases at 60 and 120 min (P more than
      0.05). Compared with pre-plasma-perfusion, there were significant decreases in
      the levels of blood alanine aminotransferase, aspartate aminotransferase, and
      ammonia (P less than 0.05); the plasma prothrombin time was significantly
      increased (P less than 0.05), the electrolytes, hematocrit level, platelet count,
      and white cell count were not affected significantly by the perfusion (P more
      than 0.05); blood pressure and body temperature were not affected significantly
      during the plasma-perfusion. CONCLUSION: Plasma-perfusion with a novel aminated
      chitosan resin is an effective and safe method for treating liver failure in this
      canine model.

PMID- 18822213
TI  - [Construction of full-length genome HBV plasmid with adefovir dipivoxil drug
      resistance gene in RT domain of polymerase].

PMID- 18822214
TI  - [Differentiation of self bone marrow mesenchymal stem cells in transplanted rat
      livers].

PMID- 18822215
TI  - [Relationships of HBV genotypes and HBV lymphocytes and clinical features of
      chronic hepatitis B patients].

PMID- 18822216
TI  - [The effects of glycine on the expression of peroxisome-proliferator-activated
      receptor gamma in nonalcoholic fatty rat livers].

PMID- 18822217
TI  - [A study on the numbers and functions of circulating CD11c+ myeloid dendritic
      cells in patients with chronic hepatitis B].

PMID- 18822218
TI  - [Significance of PD-1 up-regulation on CD8+ T lymphocytes from patients with
      chronic hepatitis B virus infection].

PMID- 18822219
TI  - [The molecular biological mechanisms of hepatocellular injury].

PMID- 18822220
TI  - [Basic and clinical research regarding hepatocyte death].

PMID- 18822222
TI  - [Advances in hepatic stellate cell functions research].

PMID- 18822221
TI  - [Application and value of anti-inflammation and liver protection therapy in the
      treatment of liver diseases].

PMID- 18822223
TI  - [Intestinal microenvironment of patients with liver disease and its effect on
      immunity].

PMID- 18822224
TI  - [Back pain: need for a new research paradigm].

PMID- 18822227
TI  - [Exenatide--an alternative to insulin in the treatment of type 2 diabetes?].
AB  - The benefits and drawbacks of exenatide as an alternative to insulin in the
      treatment of poorly regulated type 2 diabetes are reviewed. Exenatide and insulin
      have equal effects on HbA1c but exenatide causes weight-loss and improved
      postprandial glucose control. Nausea is reported by nearly half of patients
      treated with exenatide. Exenatide can be considered in the overweight patient
      without extremely elevated HbA1c but nausea could pose a substantial hurdle for
      successful treatment.

PMID- 18822228
TI  - [Global spread of meningococcal serogroup W135].
AB  - Worldwide, meningococcal meningitis and sepsis cause 500,000 cases of illness and
      50,000 deaths annually. The increase in global travel activity has resulted in a
      change in the epidemiology of infectious diseases, and an accumulation of
      evidence now indicates a connection between pilgrimage and the spread of
      meningococcal serogroup W135. During the past decade a number of cases of
      meningococcal disease caused by serogroup W135 have been observed in West Africa.
      The epidemiology of meningococcal disease in the meningitis belt has changed and
      this calls for awareness when counselling travellers.

PMID- 18822229
TI  - [Preoperative chemotherapy in operable breast cancer. A survey of a Cochrane
      review].

PMID- 18822230
TI  - [Bispectral index for improving anesthetic delivery and postoperative recovery. A
      survey of a Cochrane review].

PMID- 18822231
TI  - [Synacten test].

PMID- 18822232
TI  - [Alcoholics Anonymous and other 12-step programs].

PMID- 18822233
TI  - [Brief intervention in primary health care for patients with excessive alcohol
      drinking--is it effective?].

PMID- 18822234
TI  - [Gum chewing reduces duration of postoperative ileus].
AB  - Postoperative ileus (POI) after abdominal surgery is characterized by delayed
      passage of flatus and stool due to decreased bowel motility. Research has been
      performed in order to find new approaches such as fast track to reduce patient
      discomfort and durability of POI. One of the latest approaches attempting to
      reduce POI is gum chewing. Four controlled studies have been published on the
      subject and the results of two of these studies found a significant decrease in
      time until first passage of flatus and defaecation. The remaining two studies
      showed no significant difference, but a slight tendency towards a reduction of
      POI.

PMID- 18822235
TI  - [Cancer survival before and after initiating the Danish Cancer Control plan].
AB  - INTRODUCTION: Has there been a visible effect on cancer survival after the launch
      of the first cancer control plan in year 2000? MATERIAL AND METHODS: All cancers
      reported 1995-2003 to the Danish Cancer Registry were included. Three cohorts
      diagnosed 1995-1997, 1998-2000 and 2001-2003 were followed for death until 31
      December 2006 and age standardized 1- and 3-year relative survival was calculated
      by the cohort method. RESULTS: One-year survival increased for men from 59 to 65%
      and for women from 67 to 70%, and 3-year survival from 44 to 51% and 55 to 59%,
      respectively. The improved 3-year survival for women was after the launch of the
      cancer plan, whilst for men it was in the entire observation period. Improvement
      in 3-year survival for both sexes occurred for colon, rectum and lung cancer, and
      for bladder and prostate in men and esophagus, breast, ovary and leukemia in
      women. Worse survival was seen for oral and pharyngeal cancer in women.
      DISCUSSION: The improved trend in survival has been maintained. The cancer plan
      may improve survival before onset due to the early implementation of
      recommendations. Since improvements in surgery presents early, 3-year survival is
      relevant. The improved survival for colo-rectal, lung, bladder, esophagus and
      ovarian cancer may be related to the cancer plan. Improvement in breast cancer
      survival is likely due to screening and the DBCG continued activity, whilst
      increasing incidence of prostate cancer due to PSA testing is likely to be behind
      our observation. Longer follow-up and a timely and updated cancer registry are
      needed to fully assess the impact of the cancer plan.

PMID- 18822236
TI  - [Respiratory symptoms after the use of a painting primer product spray].
AB  - The use of waterproofing spray has been associated with the development of
      respiratory symptoms, but the pathogenetic mechanisms are unclear. We describe a
      case of acute respiratory disease with impaired diffusion developed after the use
      of a painting primer product spray (stain stop). Further investigation in aerosol
      toxicology is needed.

PMID- 18822237
TI  - [Hypokalemic thyrotoxic periodic paralysis--a rare differential diagnosis in
      patients presenting acute tetraparesis].
AB  - A 40-year-old Caucasian man was diagnosed hyperthyroid in 2001. In 2002 he
      suddenly developed a feeling of muscle weakness. Medical investigation showed
      decreased muscle strength of the legs and arms, reduced deep reflexes of the
      patella and low serum potassium. The neurological symptoms disappeared 10 hours
      later without potassium treatment. Similar diseases and symptoms appeared in
      2006. This case demonstrates that it is important to keep HTTP in mind since it
      can be the clinical manifestation of hyperthyroidism.

PMID- 18822238
TI  - [Streptococcus pneumoniae endocarditis diagnosed with polymerase chain reaction].
AB  - A 60-year old man was admitted with sepsis and meningitis of unknown aetiology.
      Underlying aortic valve endocarditis was diagnosed by echocardiography and severe
      insufficiency led to aortic valve replacement. Application of broad-range PCR to
      cusp tissue revealed a DNA product, and a diagnosis of Streptococcus pneumoniae
      endocarditis was obtained by DNA sequencing.

PMID- 18822240
TI  - Conclusions from Swiss study questioned.

PMID- 18822241
TI  - Human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS)
      case reporting in the World Health Organization European Region in 2006.
AB  - This article presents information on HIV and AIDS case reporting systems as part
      of a survey on HIV/AIDS surveillance practices in the World Health Organization
      (WHO) European Region. A standardised questionnaire was sent to the 53 national
      correspondents of the European Centre for the Epidemiological Monitoring of
      AIDS(EuroHIV). The HIV and AIDS case reporting section of the questionnaire
      comprised four parts: data collection system, HIV/AIDS case definition for
      surveillance, variables collected, and evaluation of surveillance systems).
      Individual-based data collection systems for HIV case reports have been
      implemented in 43 of 44 countries in the WHO European Region and for AIDS case
      reports in all the countries. For HIV case reports, a coded identifier is used in
      28 countries, and full names are used in 11 countries. The European AIDS case
      definition has been adopted in 35 countries(80%). Information on molecular
      epidemiology is available in 30 countries, and HIV drug resistance is monitored
      in 11 countries.HIV/AIDS case reporting systems have been evaluated for
      underreporting in 17 countries and for completeness in 11 countries.This article
      outlines the future needs for HIV/AIDS surveillance and presents recommendations
      on how to improve data comparability across European countries in the WHO region.

PMID- 18822242
TI  - Increase in VTEC cases in the south of Ireland: link to private wells?

PMID- 18822243
TI  - Detection of West Nile virus infection in horses, Italy, September 2008.

PMID- 18822244
TI  - West Nile fever in a patient in Romania, August 2008: case report.

PMID- 18822245
TI  - Nationwide outbreak of Salmonella enterica serotype gives infections in infants
      in France, linked to infant milk formula, September 2008.

PMID- 18822246
TI  - [Editorial. Diabetic foot].

PMID- 18822247
TI  - [Epidemiology of diabetic foot problems].
AB  - Since diabetes mellitus is growing at epidemic proportions worldwide, the
      prevalence of diabetes-related complications is bound to increase. Diabetic foot
      disorders, a major source of disability and morbidity, are a significant burden
      for the community and a true public health problem. Many epidemiological data
      have been published on the diabetic foot but they are difficult to interpret
      because of variability in the methodology and in the definitions used in these
      studies. Moreover, there is a lack of consistency in population characteristics
      (ethnicity, social level, accessibility to care) and how results are expressed.
      In westernized countries, two of 100 diabetic patients are estimated to suffer
      from a foot ulcer every year. Amputation rates vary considerably: incidence
      ranges from 1 per thousand in the Madrid area and in Japan to up to 20 per
      thousand in some Indian tribes in North America. In metropolitan France, the
      incidence of lower-limb amputation is approximately 2 per thousand but with
      marked regional differences, and in French overseas territories, the incidence
      rate is much higher. Nevertheless, the risk for ulceration and amputation is much
      higher in diabetics compared to the nondiabetic population: the lifetime risk of
      a diabetic individual developing an ulcer is as high as 25% and it is estimated
      that every 30s an amputation is performed for a diabetic somewhere in the world.
      As reviewed in this paper, peripheral neuropathy, arterial disease, and foot
      deformities are the main factors accounting for this increased risk. Age and sex
      as well as social and cultural status are contributing factors. Knowing these
      factors is essential to classify every diabetic using a risk grading system and
      to take preventive measures accordingly.

PMID- 18822248
TI  - [Physiopathology of the diabetic foot].
AB  - Diabetic foot ulcerations result from different physiopathological mechanisms; a
      clear understanding of them is crucial to reduce their incidence, provide early
      care, and finally delay the amputation risk. The three main diabetes
      complications involved in foot ulcerations are neuropathy, peripheral arterial
      disease, and infection. The most common pathway to ulceration is peripheral
      sensorimotor and autonomic neuropathy, leading to loss of sensitivity, foot
      deformities, high foot pressure, and dry skin. Peripheral arterial disease is
      more frequent and more serious in the diabetic population. It delays
      cicatrization and causes gangrene and finally amputation. Infection is also a
      major complication of ulceration because of its risk of spreading into deep
      tissue and bone, which increases the risk of amputation. Infection may also
      generalize and become life-threatening. These complications preferentially affect
      the foot because it is exposed to hyper pressure, neuropathy, and peripheral
      arterial disease, which cause distal lesions, and the foot is exposed to a closed
      atmosphere, a source of soaking and skin frailty. Diabetes itself may enhance the
      risk of complications stemming from the disease's long-term progression and poor
      glucose control, thereby affecting ocular and renal functions. Finally, some
      psychosocial situations such as depression syndrome or poor hygiene possibly
      enhance diabetic foot occurrence.

PMID- 18822249
TI  - [Management of a diabetic foot ulcer].
AB  - A chronic diabetic foot ulcer requires a search for the etiology. The three main
      causes to search for are poor off-loading compliance, osteomyelitis, and
      peripheral vascular disease. The level of severity is measured with the U.T.
      classification and the level of infection with the classification of the
      International Consensus on the Diabetic Foot. Peripheral vascular disease must be
      precisely evaluated by Doppler ultrasound, which describes all the arteries of
      the lower limb. Angiography is required only in case of revascularization.
      Treatment of the ulcer includes strict off-loading, topical treatment, optimal
      treatment of hyperglycemia, and antibiotic therapy on a case-by-case basis for
      osteomyelitis and/or, angioplasty or by-pass procedures. Osteomyelitis can be
      treated by associating conservative surgery, antibiotic therapy, and off-loading.
      No amputation, even of one toe, must be done without a previous vascular check
      up. Off-loading of the ulcer must be regularly checked. Poor off-loading
      compliance must be systematically investigated if the ulcer worsens or healing is
      delayed.

PMID- 18822250
TI  - [Infection and diabetic foot].
AB  - The large number of factors that influence the outcome of patients with diabetic
      foot infections calls for a multidisciplinary management of such patients.
      Infection is always the consequence of a preexisting foot wound whose chronicity
      is facilitated by the diabetic peripheral neuropathy, whereas peripheral vascular
      disease is a factor of poor outcome, especially regarding the risk for leg
      amputation. Primary and secondary prevention of IPD depends both on the efficacy
      of wound off-loading. Antibiotic treatment should only be considered for
      clinically infected foot wounds for which diagnostic criteria have recently been
      proposed by international consensus. The choice of the antibiotic regimen should
      take into account the risk for selecting bacterial resistance, and as a
      consequence, agents with a narrow spectrum of activity should be preferred.
      Respect of the measures for preventing the spread of bacterial resistance in
      diabetic foot centers is particularly important.

PMID- 18822251
TI  - [Peripheral vascular disease and diabetic foot].
AB  - Peripheral vascular disease is one component of the diabetic foot. Diabetic
      patients should be assessed for lower limb arterial disease resulting from the
      high prevalence of this complication. Medical management includes the treatment
      of vascular risk factors, anti-thrombotic agents, and walking rehabilitation.
      Vascular testing is required in the presence of a foot wound. Ischemia alone is
      implicated in only 10% of foot wounds, whereas inadequate tissue perfusion is
      often a nonhealing factor. Managing a diabetic patient with a foot wound will be
      more effective in a dedicated center providing vascular assessment, a
      multidisciplinary pre concerted plan, and vascular management. Lowering the
      number of major amputations in the diabetic population requires better arterial
      evaluation and treatment (vascular functional testing and revascularization when
      possible).

PMID- 18822252
TI  - [Diabetic foot: detection and prevention].
AB  - Foot care prevention programs can reduce the occurrence of foot ulcerations and
      amputations. The most important factor related to the development of foot ulcer
      is peripheral neuropathy, associated with loss of pain. Neuropathy can be
      associated with peripheral vascular disease and foot deformities. Five
      cornerstones for prevention should be respected, including regular examination of
      the feet and footwear, identification of high-risk patients, education of the
      patient and family, appropriate footwear, and treatment of nonulcerative
      pathology. After examination of the foot using the Semmes-Weinstein monofilament
      test, each patient can be assigned to one of the four risk categories to guide
      management. Foot care programs should be provided to high-risk categories of
      patients. Education plays an important role in prevention. The aim is to increase
      motivation and skills and enhance compliance with footwear advice. Items may
      include daily feet inspection and regular washing. Appropriate foot wear should
      protect against trauma. High-risk patients should participate in a foot care
      program set up by a multidisciplinary foot care team.

PMID- 18822253
TI  - [The French nationwide cystic fibrosis newborn screening program: strategy and
      results].
AB  - In 2002 France implemented a nationwide newborn screening program for cystic
      fibrosis (CF). The strategy combined immunoreactive trypsinogen and, in case of a
      value over the cut-off level, DNA analysis in dried blood samples at day 3. Data
      were centralized and periodically analyzed thus maintaining the percentage of
      samples requiring mutation analysis (0.6%), limiting the number of false-positive
      cases (0.1%) without increasing the number of false-negative cases (3.2%).
      3.527.353 infants were screened between 2002 and 2006. The overall cystic
      fibrosis incidence was 1/ 4136 with a wide range of regional variations. Dilemma
      case presentation occurred for 14 % of the patients; an European working group is
      actively working on this topic, attempting to establish a consensus on the
      adequate procedures. Cystic fibrosis newborn screening is feasible all over a
      nation but needs a strong organization from maternity wards to CF care centers.

PMID- 18822254
TI  - [Attachment process between an infant and his/her mother: the first year].
AB  - Attachment theory is focused upon the development of the attachment process
      organized jointly by the child and the environmental factors which contribute to
      the development of the feeling of security. The authors focus on the mother-baby
      relationships and describe the normative process of attachment relationships
      during the first year of life. The ethologic perspective of this development is
      also summarized. The steps of the developing attachment relationship are
      described. The description of motherhood is focused on the bonding process, which
      is a more immediate and biologically based process and on caregiving which is a
      symmetrical motivational system as complex as the attachment one. The main
      factors known as having an impact on the two processes are described.

PMID- 18822255
TI  - [Prevention of positional plagiocephaly].
AB  - Since the beginning of 90's, there is an increasing incidence of deformational
      plagiocephaly (DP). Based upon observational studies, some authors proposed to
      provide parents with advices about positioning infants. We recently observed that
      early specific counselling about "unrestricted motility", as suggested by E.
      Pikler, during maternity stay, is able to significantly reduce the incidence of
      DP at 4 months of life. In agreement with recent studies we did not observe a
      relationship between sleeping position and the occurrence of DP. Flattened head
      at birth was not an independent risk factor for DP at four months, suggesting
      that it could be more efficient to provide "unrestricted motility advices" to all
      parents and not only to a supposed "at-risk" population. Finally the absence of
      "unrestricted motility", rather than supine position, could be implicated in the
      increasing incidence of deformational plagiocephaly.

PMID- 18822256
TI  - [Cranial osteopathy as a complementary treatment of postural plagiocephaly].
AB  - For the majority of neonates and young infants, appropriate postures and standard
      physiotherapy succeed in preventing or correcting acquired cranial deformations
      (fetal due to restricted mobility in utero or postnatal secondary to exclusive
      dorsal decubitus). However in some cases, when postural management is not
      efficient, pediatricians will be asked by the parents about the potential
      benefits of osteopathy. What is osteopathic treatment? At first, diagnostic
      palpation will identify which suture is normally mobile with the respiratory
      cycle, and which has limited or absent mobility secondary to abnormal postures.
      Later on, the goal of the therapeutic phase is to mobilise impaired sutures, by
      various gentle maneuvers depending on the topography of the impairment. The
      treatment is not restricted to the skull but extended to the spine, pelvis and
      lower extremities which contribute to the deformative sequence. Osteopathic
      treatment belongs to complementary medicine, therefore demonstration of its
      scientific value and favorable results have to be provided. Based on randomized
      studies, the answer is yes, it significantly decreases the degree of asymmetry.
      Do postural deformations matter to the development of an healthy infant? It seems
      that the prejudice is not only esthetic but also functional, however more
      research is necessary. In conclusion, pediatricians should be more aware of the
      method and expectations: major deformative sequence since birth and increasing
      deformations despite preventive postures and standard physiotherapy are
      reasonable indications for such complementary treatment. "Preventive" osteopathy
      in maternity is not justified. Moreover osteopathy has no place in the treatment
      of craniosynostosis ; the latter belong to malformations, completely distinct
      from postural deformations.

PMID- 18822257
TI  - [Is it possible to protect the preterm infant brain and to decrease later
      neurodevelopmental disabilities?].
AB  - With improving neonatal survival for very premature babies, the challenge for
      neonatalogists is to ameliorate outcome of surviving babies. Several
      pharmacological molecules have been shown to have protective effects in different
      types of in vitro or in vivo animal models of acquired cerebral brain damages.
      However translational research and conduction of therapeutic trials in human
      remain difficult due to failure to recognize start of deleterious cascade leading
      to cerebral damage and additional toxic effect of potential protective molecules.
      This review concentrates on best evidence emerging in recent years on prevention
      on brain damage by early drug administration. It has been shown in two randomised
      trials that prenatal low-dose of magnesium sulphate does not increase paediatric
      mortality in very-preterm infants and has non significant neuroprotective effects
      on occurrence of motor dysfunction (with a 0.62 odds ratio in the French trial
      Premag and 0.71 relative risk in the Australian trial ACTOMgSO4), justifying that
      magnesium sulphate should be discussed as a stand-alone treatment or as part of a
      combination treatment, at least in the context of clinical trials. Antenatal
      corticosteroid therapy increases the survival of very-preterm infants, including
      the most immature. Moreover in an observational recent study of the Epipage
      cohort, it has been observed a significant decrease in white matter injury in the
      28-32 weeks' gestation group but no effect on long term outcome and behaviour.
      Conversely in the most immature of the 24-27 weeks' gestation group, no effect
      has been detected either in white matter injury incidence or in long term outcome
      rates. Caffeine has a protective effect since a decrease in cerebral palsy has
      been noted in the caffeine group in a randomised trial studying caffeine versus
      placebo. For what concern other widely used potential protective molecules during
      the perinatal period, there is no evidence of cerebral protection with
      indometacine, nitric oxide, eythropoietin, phenobarbital, and etamsylate. Due to
      their specific properties, a careful evaluation of aspirin, anaesthetic drugs and
      tocolytics should be done in the next months.

PMID- 18822258
TI  - [Exogenous surfactant therapy: new synthetic surfactants].
AB  - There are numerous pulmonary conditions in which qualitative or quantitative
      anomalies of the surfactant system have been demonstrated. In premature newborns
      with immature lungs, a functional deficit in surfactant is the main
      physiopathologic mechanism of the neonatal respiratory distress syndrome (RDS).
      Since the landmark pilot study of Fujiwara, published more than 20 years ago, the
      efficacy of exogenous surfactant for the treatment of neonatal RDS has been
      established by numerous controlled studies and meta-analyses. Enlightened by a
      growing insight into both the structure and function of the different surfactant
      components, a new generation of synthetic surfactants has been developed. Various
      complementary approaches have confirmed the fundamental role of the two
      hydrophobic proteins, SP-B and SP-C, in the surfactant system, thus opening the
      way to the design of analogues, either by chemical synthesis or expression in a
      prokaryotic system. An example of these peptide-containing synthetic surfactant
      preparations, lucinactant (Surfaxin), has been recently tested in comparison to a
      synthetic surfactant that does not contain protein as well as to animal derived
      surfactant preparations. Major clinical outcomes between lucinactant and animal
      derived surfactant preparations were fund similar in two randomized controlled
      trials, opening the way to a new generation of synthetic surfactants in the near
      future.

PMID- 18822259
TI  - [Prematurity and neonatal screening].
AB  - Neonatal screening for metabolic and endocrine diseases has clear benefits for
      full-term infants by providing early diagnosis and treatment to prevent or limit
      the severe adverse outcomes which occur in untreated infants. The situation of
      preterm infants is more complicated, with an increased risk of false-positive as
      well as false-negative screening results. The aim of this work was to evaluate
      the impact of prematurity in screening strategies in order to answer practical
      questions: is there a need or not to adjust cut-off values in accord to
      gestational parameters? Is there a need or not to repeat screening tests at a
      later age?

PMID- 18822260
TI  - [Editorial].

PMID- 18822261
TI  - [Prostate cancer: news in 2008].
AB  - In 2007, prostate cancer was the subject of a large number of communications in
      international conferences. The most innovating studies that are likely to modify
      patient management were selected. The topics included cancer detection, active
      surveillance, surgery and treatment of urinary incontinence after prostatectomy,
      radiotherapy, and high-intensity focalized ultrasound (HIFU). Current hormone
      treatment modalities as well as the new therapies for hormone-resistant prostate
      cancer management were also evaluated in detail.

PMID- 18822262
TI  - [Bladder cancer: news in 2008].
AB  - In 2007, urothelial cancers were the subject of a large number of varied
      communications in international conferences. Some of the most innovating studies
      likely to modify patient management were selected. Regarding non muscle-invading
      tumors, maintenance treatments using intravesical instillations were emphasized.
      Laser and laparoscopy were assessed in urothelial tumors of the upper urinary
      tract. Finally, new radiochemotherapy protocols have appeared for infiltrating
      bladder tumors. Extended lymphadenectomy and laparoscopy were also evaluated in
      detail.

PMID- 18822263
TI  - [Cancers of the penis and testicle: news in 2008].
AB  - In the 2007 international conferences, a certain number of communications were
      devoted to the cancers of the male external genital organs. The most innovating
      studies were selected. In the pure testicular seminomas, radiotherapy was
      compared to carboplatin in adjuvant treatment. Active surveillance of stage Ia
      germinal tumors was evaluated. In penis cancer management, curietherapy in early
      stage treatment was reported, and sentinel lymph node detection was covered in
      many studies.

PMID- 18822264
TI  - [Kidney cancer: news in 2008].
AB  - The most innovating studies presented at the 2007 international conferences in
      the field of kidney cancer were selected. The notable topics presented covered
      diagnostic biopsies and the growing place of conservative surgery and laparoscopy
      in kidney cancer management. For cases with poor prognosis, the new anti
      angiogenic therapies were thoroughly evaluated.

PMID- 18822265
TI  - Monitoring Plasmodium falciparum chloroquine resistance in Yunnan Province,
      China, 1981-2006.
AB  - The emergence and spread of drug resistant malaria parasites are an important
      factor contributing to the global resurgence of malaria, demonstrating the
      essence of drug resistance surveillance in endemic areas. In the malarious border
      regions of Yunnan Province, China, we have selected three study sites to monitor
      in vitro and in vivo resistance of Plasmodium falciparum parasites to chloroquine
      (CQ) from 1981 to 2006. In vitro studies using the microtest clearly showed high
      degree of CQ resistance in the early 1980s, when CQ was replaced by artemether
      monotherapy for falciparum malaria. In subsequent in vitro surveys performed in
      the early 1990s and 2003-2004, we found reductions in both the concentrations
      inhibiting 50% parasite growth (IC(50)s) and the percentage of resistant
      parasites at all study sites, although the degrees of the reduction varied among
      sites. Even though amodiaquine has never been used in this area, there were
      consistently high levels of resistance to this drug, confirming crossresistance
      between CQ and amodiaquine. In vivo clinical studies were consistent with the
      results of the in vitro assays. The overall rate of resistant clinical cases
      decreased from 97% in 1981-1983 to 40% in 2005-2006. Collectively, whereas a
      general trend of reduction in CQ resistance was observed in Yunnan, variations
      among sites existed in this relatively small area, probably as the result of both
      geographical heterogeneity of malaria epidemiology in Yunnan and different levels
      of CQ resistance in neighboring countries.

PMID- 18822266
TI  - Diagnosis of cryptosporidiosis using PCR or auramine O with LED fluorescent
      microscopy: which end of the stick?

PMID- 18822267
TI  - Neopterin, a marker of immune response, and 8-hydroxy-2'-deoxyguanosine, a marker
      of oxidative stress, correlate at high age as determined by automated
      simultaneous high-performance liquid chromatography analysis of human urine.
AB  - Using an established high-performance liquid chromatography (HPLC) method based
      on anion exchange chromatography, fraction collection, and electrochemical
      detection, the oxidative DNA damage marker 8-hydroxy-2'-deoxyguanosine (8-OH-dG)
      can be analyzed rapidly and precisely in human urine samples. In addition, by
      ultraviolet (UV) detection, it was shown recently that it is possible to
      simultaneously analyze creatinine and 7-methylguanine (m(7)Gua), an RNA
      degradation product, in urine. By adding a fluorescence detector to the HPLC
      system, we now report that it is also possible to detect pteridins such as
      neopterin and biopterin. The fluorescence detection was evaluated in detail for
      neopterin, an immune response and tumor marker. The urinary content of neopterin,
      assessed by using the HPLC method, was verified with a commercial neopterin
      enzyme-linked immunosorbent assay (ELISA) kit as indicated by the high
      correlation between the two methods (r=0.98). In urinary samples from 58 young
      healthy individuals (male and female nonsmokers, ages 19-39 years), it was found
      that there was no significant correlation (r=-0.04) between the levels of 8-OH-dG
      and neopterin (as normalized to urinary creatinine levels). In contrast, in
      urinary samples from 60 old healthy individuals (male and female nonsmokers, ages
      60-86 years), there was a significant correlation (r=0.47) found between the
      levels of 8-OH-dG and neopterin (as normalized to urinary creatinine levels).
      These findings strongly indicate that the higher level of immune response that
      was correlating with old age contributes significantly to the higher level of
      oxidative damage as assessed in the form of 8-OH-dG. Using this type of HPLC
      system, it is possible to evaluate oxidative DNA damage and immune response
      simultaneously using the respective urinary markers. These data may contribute to
      understanding of the pathophysiology of diseases such as infections and tumor
      progression where both oxidative stress and immune response occur simultaneously.

PMID- 18822268
TI  - High sensibility to reactivation by acidic lipids of the recombinant human plasma
      membrane Ca2+-ATPase isoform 4xb purified from Saccharomyces cerevisiae.
AB  - The human plasma membrane Ca2+ pump (isoform 4xb) was expressed in Saccharomyces
      cerevisiae and purified by calmodulin-affinity chromatography. Under optimal
      conditions the recombinant enzyme (yPMCA) hydrolyzed ATP in a Ca2+ dependent
      manner at a rate of 15 micromol/mg/min. The properties of yPMCA were compared to
      those of the PMCA purified from human red cells (ePMCA). The mobility of yPMCA in
      SDS-PAGE was the expected for the hPMCA4xb protein but slightly lower than that
      of ePMCA. Both enzymes achieved maximal activity when supplemented with acidic
      phospholipids. However, while ePMCA in mixed micelles of phosphatidylcholine
      detergent had 30% of its maximal activity, the yPMCA enzyme was nearly inactive.
      Increasing the phosphatidylcholine content of the micelles did not increase the
      activity of yPMCA but the activity in the presence of phosphatidylcholine
      improved by partially removing the detergent. The reactivation of the detergent
      solubilized yPMCA required specifically acidic lipids and, as judged by the
      increase in the level of phosphoenzyme, it involved the increase in the amount of
      active enzyme. These results indicate that the function of yPMCA is highly
      sensitive to delipidation and the restitution of acidic lipids is needed for a
      functional enzyme.

PMID- 18822269
TI  - AFM for structure and dynamics of biomembranes.
AB  - We review structure and dynamic measurements of biomembranes by atomic force
      microscopy (AFM). We focus mainly on studies involving supported lipid bilayers
      (SLBs), particularly formation by vesicle rupture on flat and corrugated
      surfaces, nucleation and growth of domains in phase-separated systems, anesthetic
      lipid interactions, and protein/peptide interactions in multicomponent systems.
      We show that carefully designed experiments along with real-time AFM imaging with
      superior lateral and z resolution (0.1 nm) have revealed quantitative details of
      the mechanisms and factors controlling vesicle rupture, domain shape and size,
      phase transformations, and some model biological interactions. The AFM tip can
      also be used as a mechanical transducer and incorporated in electrochemical
      measurements of membrane components; therefore, we touch on these important
      applications in both model and cell membranes.

PMID- 18822270
TI  - Lipid domains in bacterial membranes and the action of antimicrobial agents.
AB  - There has been increasing interest in recent years in describing the lateral
      organization of membranes and the formation of membrane domains. Much of the
      focus in this area has been on the formation of cholesterol-rich domains in
      mammalian membranes. However, it is likely that there are domains in all
      biological membranes. One of the challenges has been to define the chemical
      composition, lifetime and size of these domains. There is evidence that bacteria
      have domains that are enriched in cardiolipin. In addition, the formation of
      lipid domains can be induced in bacteria by clustering negatively charged lipids
      with polycationic substances. Many antimicrobial compounds have multiple positive
      charges. Such polycationic compounds can sequester anionic lipids to induce lipid
      phase separation. The molecular interactions among lipids and their lateral
      packing density will be different in a domain from its environment. This will
      lead to phase boundary defects that will lower the permeability barrier between
      the cell and its surroundings. The formation of these clusters of anionic lipids
      may also alter the stability or composition of existing membrane domains that may
      affect bacterial function. Interestingly many antimicrobial agents are
      polycationic and therefore likely have some effect in promoting lipid phase
      segregation between anionic and zwitterionic lipids. However, this mechanism is
      expected to be most important for substances with sequential positive charges
      contained within a flexible molecule that can adapt to the arrangement of charged
      groups on the surface of the bacterial cell. When this mechanism is dominant it
      can allow the prediction of the bacterial species that will be most affected by
      the agent as a consequence of the nature of the lipid composition of the
      bacterial membrane.

PMID- 18822271
TI  - JNK1 regulates histone acetylation in trigeminal neurons following chemical
      stimulation.
AB  - Trigeminal nerve fibers in nasal and oral cavities are sensitive to various
      environmental hazardous stimuli, which trigger many neurotoxic problems such as
      chronic migraine headache and trigeminal irritated disorders. However, the role
      of JNK kinase cascade and its epigenetic modulation of histone remodeling in
      trigeminal ganglion (TG) neurons activated by environmental neurotoxins remains
      unknown. Here we investigated the role of JNK/c-Jun cascade in the regulation of
      acetylation of H3 histone in TG neurons following in vitro stimulation by a neuro
      inflammatory agent, mustard oil (MO). We found that MO stimulation elicited JNK/c
      Jun pathway significantly by enhancing phospho-JNK1, phospho-c-Jun expression,
      and c-Jun activity, which were correlated with an elevated acetylated H3 histone
      in TG neurons. However, increases in phospho-c-Jun and c-Jun activity were
      significantly blocked by a JNK inhibitor, SP600125. We also found that altered H3
      histone remodeling, assessed by H3 acetylation in triggered TG neurons, was
      reduced by SP600125. The study suggests that the activated JNK signaling in
      regulation of histone remodeling may contribute to neuro-epigentic changes in
      peripheral sensory neurons following environmental neurotoxic exposure.

PMID- 18822272
TI  - Molecular NMR T2 values can predict cartilage stress-relaxation parameters.
AB  - Articular cartilage lines synovial joints and functions as a low-friction
      deformable tissue to enable smooth and stable joint articulation. The objective
      of this study was to determine the relationships between cartilage stress
      relaxation properties and the collagen and GAG NMR transverse relaxation times
      (T(2)) toward understanding mechanisms of cartilage viscoelasticity. Stress
      relaxation tests were performed on both cultured and enzymatically digested
      bovine cartilage, followed by measurements of both the collagen and GAG T(2)
      using the Call-Purcell-Meiboom-Gill pulse sequence. The peak and equilibrium
      stresses were correlated with the GAG T(2), and the stress-relaxation time
      constant was correlated with the collagen T(2). Multiple linear regression models
      were successful in using the specific T(2) values to predict the stress
      relaxation properties. As a model of osteoarthritis, enzymatic digestion with
      collagenase and testicular hyaluronidase had weak effects on T(2) values. These
      data present a complex picture of cartilage mechanical behavior, with cartilage
      stiffness associated with the GAG T(2) values and the stress-relaxation time
      constant associated with the collagen T(2).

PMID- 18822273
TI  - The E163K DJ-1 mutant shows specific antioxidant deficiency.
AB  - Recent discoveries of genetic mutations linked to familial forms of Parkinson's
      disease (PD), including mutations in DJ-1, have provided insights into the
      pathogenesis of sporadic PD. Recently, a novel homozygous missense mutation in
      the gene encoding human DJ-1 protein resulting in the E163K amino acid
      substitution has been reported. This mutation is associated with early-onset and
      clinical presentations that include parkinsonism, cognitive decline, and
      amyotrophic lateral sclerosis. The specific effect of this mutation on the
      function of DJ-1 protein as it relates to disease pathogenesis is currently
      unknown. Herein we show that the E163K pathogenic mutant retains similar
      properties to wild-type DJ-1 protein as it relates to protein stability,
      solubility, and dimerization. However, we show that the E163K mutant loses the
      ability to protect against oxidative stress while demonstrating a reduced
      redistribution towards mitochondria, but retains the ability to mitigate toxicity
      due to mitochondrial stress and proteasomal impairment. These findings suggest
      that DJ-1 influences several neuroprotective pathways and that the E163K mutation
      impairs the mechanism that is more specific to oxidative stress.

PMID- 18822274
TI  - Effects of dopamine and NMDA receptors on cocaine-induced Fos expression in the
      striatum of Fischer rats.
AB  - Cocaine is an addictive psychostimulant that induces immediate early gene (IEG)
      expression by activating dopamine (DA) D1 and glutamate NMDA receptors in the
      striatum. In this study, we show that a single cocaine administration (30 mg/kg)
      time-dependently increases ERK phosphorylation, c-Fos and FosB protein
      expression, and MKP-1 phosphorylation (p-MKP-1), in the caudate-putamen (CPu) and
      nucleus accumbens (NAc) of Fischer rats. In the CPu, 1 h after cocaine injection,
      the increase in c-Fos and FosB protein expressions is totally abolished by pre
      administration of DA-D1 receptor antagonist, SCH23390. In the NAc, SCH23390 also
      inhibits cocaine-induced c-Fos protein expression. The pre-treatment of NMDA
      receptor antagonist, MK801, partially reduces cocaine-activated c-Fos protein
      expression in the CPu. Furthermore, the escalation of p-MKP-1 after acute cocaine
      administration is dependent on both DA-D1 and NMDA receptor activation in both
      brain regions examined. Our data suggest that cocaine may modulate ERK pathway
      signaling through the activation of DA-D1 and NMDA receptors, subsequently
      influencing the IEG protein expression.

PMID- 18822275
TI  - NMDA modulation of GABA transporter current in carp retinal horizontal cells.
AB  - In the present study, the modulatory effect of NMDA on GABA transporter current
      was investigated on enzymatically isolated horizontal cells of carp retina. After
      application of NMDA (0.1 mM) for 50 s, the GABA transporter current elicited by
      GABA (1 mM) was decreased to 78.07+/-3.10% (n=5) of the control level. When the
      extracellular Ca(2+) was removed from the Ringer's solution, the NMDA inhibitory
      effect on the GABA transporter current was eliminated. The suppression effect
      could be attenuated when the Ca(2+) release and Ca(2+) uptake of intracellular
      Ca(2+) store were blocked after the cell had been pre-incubated with 20 muM
      ryanodine plus 2 muM thapsigargin. Application of 10 mM BAPTA in intracellular
      solution also suppressed the NMDA modulation of GABA transporters. These results
      suggest that the activation of NMDA receptors inhibits GABA transporter-mediated
      current by affecting Ca(2+) processes in the retinal horizontal cells.

PMID- 18822276
TI  - Differential effects of the dopamine neurotoxin MPTP in animals with a partial
      deletion of the GDNF receptor, GFR alpha1, gene.
AB  - Glial cell line-derived neurotrophic factor (GDNF), a member of the transforming
      growth factor beta (TGFbeta) superfamily, is a potent neurotrophic protein
      promoting the survival and maintenance of dopaminergic (DA) neurons in the
      substantia nigra during development and adulthood. DA neurons that project to the
      striatum in the nigrostriatal pathway express GDNF receptors, GFR alpha1. The
      purpose of this study was to determine whether these neurons are especially
      sensitive to neurotoxic insults. Therefore, we examined effects of the
      dopaminergic toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on
      locomotion and DA neurons in 26-month-old male GFR alpha1 heterozygous (GFR
      alpha1(+/-)) mice compared to aged-matched wild-type (WT) littermates. MPTP gave
      rise to increased locomotion, regardless of genotype, while GFR alpha1(+/-) mice
      treated with saline exhibited lower spontaneous locomotion, compared to WT mice.
      Moreover, GFR alpha1(+/-) saline mice had fewer TH-positive neurons, greater
      expression of inflammatory markers (CD45 immunostaining and phosphorylated p38
      MAPK) in the nigra, and reduced striatal TH staining. MPTP exacerbated these
      effects, with the lowest density of striatal TH and highest density of nigral
      CD45 and phospho-p38 MAPK immunoreactivity observed in GFR alpha1(+/-) mice. The
      findings point to increased sensitivity of the DAergic system with age and
      neurotoxic exposure as a result of a genetic reduction of GFR alpha1.

PMID- 18822277
TI  - 17beta-estradiol affects GABAergic transmission in developing hippocampus.
AB  - Estrogens are potent modulators of the nervous system. In particular, 17beta
      estradiol was shown to affect GABAergic synaptic transmission in hippocampus of
      adult animals in vivo but much less is known on the impact of this hormone on the
      GABAergic system in the developing brains. We have recently shown that phasic and
      tonic GABAergic transmissions are strongly modulated upon long-term treatment
      with exogenous 17beta-estradiol in hippocampal neurons developing in vitro. To
      check for the long-term estrogen effect in a more physiological developmental
      model, we have investigated the GABAergic transmission in developing brains of P7
      P40 animals, injected daily with 17beta-estradiol. We have found that such a
      treatment clearly increased GABAergic mIPSC frequency and amplitude while the
      onset and decay of mIPSCs were shortened. These effects were statistically
      significant in the youngest considered age group (P7-P13) with a tendency to
      disappear in older animals. Long-term treatment with estradiol did not change the
      susceptibility of mIPSC amplitude to upregulation by flurazepam while mIPSC decay
      was prolonged by this drug to a larger extent in 17beta-estradiol-treated
      animals. 17beta-estradiol strongly upregulated GABAergic tonic current but again
      this effect was restricted to the youngest group of animals. We conclude that
      17beta-estradiol strongly modulates the GABAergic synaptic transmission but this
      effect critically depends on the animal age being the most prominent in youngest
      animals.

PMID- 18822278
TI  - Inhibition of thioredoxin reductase by mansonone F analogues: Implications for
      anticancer activity.
AB  - Mammalian thioredoxin reductase (TrxR), a ubiquitous selenocysteine containing
      oxidoreductase, catalyzes the NADPH-dependent reduction of oxidized thioredoxin
      (Trx). TrxR has been suggested as a potential target for anticancer drugs
      development for its overexpression in human tumors and its diverse functions in
      intracellular redox control, cell growth and apoptosis. Mansonone F (MF)
      compounds have been shown to exhibit antiproliferative effects, but their complex
      mechanisms are unknown. In the present study, we have investigated the effects of
      some synthesized MF analogues on TrxR and HeLa cells. The studies of the mode of
      inhibition and the interactions of IG3, one of the most potent MF analogues, with
      TrxR showed MF compounds could be partly reduced by the C-terminal selenolthiol
      active site, and possibly by the N-terminal dithiol motif and/or FAD domain of
      TrxR simultaneously, accompanied by redox cycling with the generation of
      superoxide anion radicals. In addition, MF analogues exhibited the potential to
      inhibit the growth of HeLa cells and reduce TrxR activity in cell lysates. The
      cell cycle was arrested in G2/M phase and apoptosis was induced in a dose
      dependent manner. Furthermore, our results showed that IG3-treated HeLa cells
      induced the change of intracellular ROS. Taken together, the reported results
      here suggest that inhibition of TrxR by MF analogues provides a possible complex
      mechanism for explaining the anticancer activity of MF compounds.

PMID- 18822279
TI  - Genetic and epigenetic stability of cryopreserved and cold-stored hops (Humulus
      lupulus L.).
AB  - Conventional cold storage and cryopreservation methods for hops (Humulus lupulus
      L.) are available but, to our knowledge, the genetic and epigenetic stability of
      the recovered plants have not been tested. This study analyzed 51 accessions of
      hop using the molecular techniques, Random Amplified DNA Polymorphism (RAPD) and
      Amplified Fragment Length Polymorphism (AFLP), revealing no genetic variation
      among greenhouse-grown controls and cold stored or cryopreserved plants.
      Epigenetic stability was evaluated using Methylation Sensitive Amplified
      Polymorphism (MSAP). Over 36% of the loci were polymorphic when the cold and cryo
      treated plants were compared to greenhouse plants. The main changes were
      demethylation events and they were common to the cryopreserved and cold stored
      plants indicating the possible effect of the in vitro establishment process, an
      essential step in both protocols. Protocol-specific methylation patterns were
      also detected indicating that both methods produced epigenetic changes in plants
      following cold storage and cryopreservation.

PMID- 18822280
TI  - Cryopreservation of kangaroo spermatozoa using alternative approaches that reduce
      cytotoxic exposure to glycerol.
AB  - Alternative techniques for the cryopreservation of kangaroo spermatozoa that
      reduced or eliminated the need for glycerol were investigated including; (1)
      freezing spermatozoa with 20% glycerol in pre-packaged 0.25 mL Cassou straws to
      enable rapid dilution of the glycerol post-thaw, (2) investigating the efficacy
      of 20% (v/v) dimethyl sulphoxide (DMSO) and dimethylacetamide (DMA-10%, 15% and
      20% v/v) as cryoprotectants and (3) vitrification of spermatozoa with or without
      cryoprotectant (20% v/v glycerol, 20% v/v DMSO and 20% v/v DMA). Immediate in
      straw post-thaw dilution of 20% glycerol and cryopreservation of spermatozoa in
      20% DMSO produced no significant improvement in post-thaw viability of kangaroo
      spermatozoa. Spermatozoa frozen in 20% DMA showed post-thaw motility and plasma
      membrane integrity of 12.7+/-1.9% and 22.7+/-5.4%, respectively, while kangaroo
      spermatozoa frozen by ultra-rapid freezing techniques showed no evidence of post
      thaw viability. The use of 10-20% DMA represents a modest but significant
      improvement in the development of a sperm cryopreservation procedure for
      kangaroos.

PMID- 18822281
TI  - Multiplicative interactions to enhance gabapentin to treat neuropathic pain.
AB  - We previously reported that gabapentin activates the bulbospinal-spinal
      noradrenergic-cholinergic pathway to produce analgesia in rats after nerve
      injury. Also, gabapentin interacts synergistically with a cholinesterase
      inhibitor donepezil to produce analgesia. Duloxetine, a serotonin/noradrenaline
      re-uptake inhibitor, has been used for the treatment of neuropathic pain and
      should amplify the noradrenergic mechanisms recruited by gabapentin. In the
      present study, we determined the interaction between duloxetine and gabapentin
      with and without donepezil when administered by the clinically preferred oral
      route in rats after spinal nerve ligation. The ED(50) value of gabapentin,
      donepezil, and duloxetine to reduce mechanical hypersensitivity after nerve
      injury was 45, 3.7, and 32 mg/kg, respectively. In the examination of two drug
      combinations, oral duloxetine with either gabapentin or donepezil were additive
      to reduce hypersensitivity. The combination of all three drugs yielded a
      synergistic interaction with an observed ED(50) at 1/4th the predicted dose of
      additivity, likely due to the gabapentin-donepezil interaction. This three drug
      combination did not affect motor coordination or show signs of sedation in the
      rotarod test. Analgesia by the combination of these three drugs was reversed by
      intrathecal injection either of the alpha(2)-adrenoceptor antagonist idazoxan or
      by the muscarinic receptor antagonist atropine. These results suggest that the
      combination of these drugs, which stimulate and augment the bulbospinal-spinal
      noradrenergic-cholinergic pathway, lowers the dose requirement for each drug to
      reduce hypersensitivity after nerve injury without sedative effects. The current
      study provides the rationale for clinical study of the combination of gabapentin,
      donepezil and duloxetine to treat neuropathic pain.

PMID- 18822282
TI  - SONU20176289, a compound combining partial dopamine D(2) receptor agonism with
      specific serotonin reuptake inhibitor activity, affects neuroplasticity in an
      animal model for depression.
AB  - We investigated the efficacy of SONU20176289, a member of a group of novel
      phenylpiperazine derivatives with a mixed dopamine D(2) receptor partial agonist
      and specific serotonin reuptake inhibitor (SSRI) activity, in a chronic stress
      model of depression in male tree shrews. Animals were subjected to a 7-day period
      of psychosocial stress before treatment for 28 days with SONU20176289 (6
      mg/kg/day, p.o.), during which stress was maintained. Stress reduced the in vivo
      brain concentrations of N-acetyl-aspartate, total creatine, and choline
      containing compounds, as measured by localized proton magnetic resonance
      spectroscopy. Post mortem analyses revealed a reduced adult dentate cell
      proliferation and a decreased GluR2 expression in the prefrontal cortex. All
      these alterations were prevented by concomitant administration of SONU20176289.
      The results provide further support to the concept that antidepressant treatments
      may act by normalizing disturbed neuroplasticity, and indicate that combining
      dopamine D(2) receptor agonism with SSRI activity may serve as an effective tool
      in the treatment of depressive/anxiety syndromes.

PMID- 18822283
TI  - DDTD, an isoflavone derivative, induces cell apoptosis through the reactive
      oxygen species/apoptosis signal-regulating kinase 1 pathway in human osteosarcoma
      cells.
AB  - Osteosarcoma is the most common primary bone tumor associated with childhood and
      adolescence. In the present study, we investigated the anticancer effect of a new
      isoflavone derivative, 3',4'-dichloro-3-(3,4-dichlorophenylacetyl)-2,4,6
      trihydroxydeoxybenzoin (DDTD) in human osteosarcoma cells. DDTD induced cell
      apoptosis in human osteosarcoma cell lines (including: U2OS, MG-63, Saos2 and ROS
      17/2.8). We found that the accumulation of reactive oxygen species is a critical
      mediator in DDTD-induced cell death. DDTD induced apoptosis signal-regulating
      kinase 1 (ASK1) dephosphorylation and its dissociation from 14-3-3. Treatment of
      osteosarcoma cells with DDTD induced p38 and p53 phosphorylation. Transfection
      with ASK1, mitogen activated protein kinase (MAPK) kinase (MKK)3/6, and p38 small
      interfering RNA (siRNA) antagonized the DDTD-induced cell apoptosis. DDTD also
      triggered the mitochondrial apoptotic pathway, as indicated by a change in
      Bax/Bcl2 ratio and Caspase-9 activation. Bax knockdown using a Bax siRNA strategy
      reduced Bax expression and subsequent cell death. In addition, transfection of
      cells with ASK1, MKK3/6, and p38 siRNA reduced DDTD-induced p38 activation, p53
      phosphorylation and Bax expression. These results suggest that DDTD generates
      reactive oxygen species and activates the ASK1-MKK3/6-p38-p53-Bax pathway to
      cause osteosarcoma cell death.

PMID- 18822284
TI  - Direct effect of light on 24-h variation of aqueous humor protein concentration
      in Sprague-Dawley rats.
AB  - Sprague-Dawley rats 10-12 weeks of age were entrained to a standard light-dark
      cycle with lights turned on at 6 am and off at 6 pm. Variations of 24-h aqueous
      humor protein concentration were determined. Samples were taken every 4h (N=10
      14) under the standard light-dark condition at 8 pm, midnight, 4 am, 8 am, noon,
      and 4 pm. Under an acute constant dark condition, when lights were not turned on
      at 6 am, samples were collected at 8 am, noon, 4 pm, and 8 pm. Aqueous humor
      protein concentrations under the standard light-dark condition were found in the
      range of 0.305+/-0.115 mg/ml (mean+/-SD, N=10) at midnight to 1.505+/-0.342 mg/ml
      (N=14) at noon. The 3 light-phase protein concentrations were each higher than
      the 3 dark-phase concentrations. Aqueous humor protein concentrations at 8 am,
      noon, and 4 pm under the acute constant dark condition were each higher than the
      concentrations at 8 pm (after both 2h and 26 h in the dark), midnight, and 4 am,
      demonstrating an endogenously driven 24-h pattern. At 8 am, noon, and 4 pm,
      protein concentrations were 56-147% higher when exposed to light. Intraocular
      pressure (IOP) was monitored using telemetry in separate groups of light-dark
      entrained rats under the standard light-dark condition and the acute constant
      dark condition. The 24-h IOP pattern was inverse to the 24-h pattern of aqueous
      humor protein concentration under the standard light-dark condition, and this IOP
      pattern was not altered by the acute constant dark condition. In conclusion, an
      endogenously driven 24-h variation of aqueous humor protein concentration
      occurred in Sprague-Dawley rats with higher concentrations during the light-phase
      than the dark-phase. This endogenous pattern of protein concentration was
      accentuated by a direct effect of light, which was unrelated to the 24-h pattern
      of IOP.

PMID- 18822285
TI  - VEGF overexpression improves mice cognitive abilities after unilateral common
      carotid artery occlusion.
AB  - Angiogenesis and neurogenesis are adaptive responses protecting cerebral tissue
      from hypoxic-ischemic injury. Both processes seem to be governed by hypoxia
      induced growth factors, of which vascular endothelial growth factor (VEGF) is a
      prominent example. The aim of this study was to investigate the influence of VEGF
      overexpression (V1 mice) on mice cognitive function and cerebral structure under
      moderate cerebral oligemia. In 33 V1 and wild-type (wt) mice, the left common
      carotid artery was permanently occluded (CCAO) under acute (48 h) and subchronic
      (12 days) conditions. Sham operation was performed in 35 mice (controls).
      Psychometric testing was done using holeboard test and Morris Water Maze system,
      immunohistochemistry was performed for detection of cerebral apoptosis, nestin
      and CD31 expression. The results show that under control conditions V1 mice
      showed better spatial cognitive abilities as compared to their wt littermates.
      During CCAO, time and distance to reach a hidden platform in Water Maze were
      shorter in V1 mice as compared to wt animals, indicative of faster learning and
      better spatial memory processes. While no signs of necrosis or apoptosis were
      detected, immunohistochemistry showed that VEGF transgenity was related to higher
      number of nestin-positive precursor cells. Finally, acute CCAO was paralleled by
      a reduction of CD31 staining in wt but not V1 mice. We conclude that VEGF
      overexpression led to a protective effect on cognitive function, because V1 mice
      showed evidence for faster spatial learning and better memory, as well as an
      increased number of neuronal precursor cells and a prevention of endothelial cell
      loss after CCAO.

PMID- 18822286
TI  - Schistosoma mansoni: Microarray analysis of gene expression induced by host sex.
AB  - Schistosoma mansoni is a digenetic trematode and a human parasite responsible for
      high social and economic impact. Although some authors have studied the effect of
      host hormones on parasites, not much is known about the effects of host sex on
      gene expression in Schistosomes. In order to study gene transcripts associated
      with the host sex, we compared the gene expression profiles of both male and
      female unisexual adult S. mansoni parasites raised on either male or female
      hosts, using DNA microarrays. Our results show that host sex caused differential
      expression of at least 11 genes in female parasites and of 134 in male parasites.
      Of the differentially expressed genes in female worms, 10 were preferentially
      expressed in female worms from male mice, while of the 134 differentially
      expressed genes in male parasites, 79 (59%) were preferentially expressed in
      worms from female mice. Further investigation of the role of each of those genes
      will help understand better their importance in the pathogenesis of
      Schistosomiasis.

PMID- 18822287
TI  - Bioluminescence imaging of hepatitis B virus enhancer and promoter activities in
      mice.
AB  - By bioluminescence imaging and hydrodynamic gene transfer technology, the
      activities of hepatitis B virus (HBV) promoters and the effects of HBV enhancers
      on these promoters in mice under true physiological conditions have been
      assessed. Our studies reveal that either of the two HBV enhancers can stimulate
      HBV major promoter activity in hepa 1-6 cells (in vitro) and in mouse liver (in
      vivo), and the enhancer effects on the three promoters (S1, S2 and X promoter)
      are markedly greater in vivo than in vitro. The two HBV enhancers have no
      cooperative action on HBV promoters in vitro or in vivo.

PMID- 18822289
TI  - Self-interaction of soluble and surface-bound beta2-glycoprotein I and its
      enhancement by lupus anticoagulants.
AB  - Antiphospholipid antibodies found in antiphospholipid syndrome are autoantibodies
      to phospholipid-binding proteins, such as beta2-glycoprotein I (beta2GPI). We
      have previously reported that among these antibodies, the so-called lupus
      anticoagulants (LAs) augment beta2GPI binding to the phospholipid membrane
      surface, which is associated with the pathological action of LAs. However, the
      molecular mechanisms underlying this augmentation are uncertain. Here we show
      that beta2GPI, which is monomeric in solution, self-interacts at the interface of
      soluble and surface-bound molecules. In addition, this self-interaction is
      enhanced by LA-positive, but not LA-negative, anti-beta2GPI monoclonal
      antibodies. This study suggests that beta2GPI self-interaction upon surface
      binding could be involved in the LA-induced potentiation of beta2GPI binding to
      the phospholipid surface.

PMID- 18822290
TI  - Imaging the assembly and disassembly kinetics of cis-SNARE complexes on native
      plasma membranes.
AB  - Mild sonication of eukaryotic cells produces native plasma membrane sheets that
      retain their docked organelles, cytoskeleton structures and cytoplasmic
      complexes. While the delicate organization of membranous protein complexes
      remains undisturbed, their inner plasmalemmel leaflet can be rapidly exposed to
      bathing solutions, enabling specific biochemical manipulations. Here, we apply
      this system to track membrane-biochemistry kinetics. We monitor soluble NSF
      attachment protein receptor (SNARE) complex assembly and disassembly on the
      plasma membrane at high time resolution. The results suggest two-phase kinetics
      for the assembly process and dependence of the disassembly kinetics on both N
      ethyl maleimide-sensitive factor (NSF) and soluble NSF-attachment protein (alpha
      SNAP) concentrations.

PMID- 18822291
TI  - Evolution of the apicoplast and its hosts: from heterotrophy to autotrophy and
      back again.
AB  - The photosynthetic origin of apicomplexan parasites was proposed upon the
      discovery of a reduced non-photosynthetic plastid termed the apicoplast in their
      cells. Although it is clear that the apicoplast has evolved through a secondary
      endosymbiosis, its particular origin within the red or green plastid lineage
      remains controversial. The recent discovery of Chromera velia, the closest known
      photosynthetic relative to apicomplexan parasites, sheds new light on the
      evolutionary history of alveolate plastids. Here we review our knowledge on the
      evolutionary history of Apicomplexa and particularly their plastids, with a focus
      on the pathway by which they evolved from free-living heterotrophs through
      photoautotrophs to omnipresent obligatory intracellular parasites. New sequences
      from C. velia (histones H2A, H2B; GAPDH, TufA) and phylogenetic analyses are also
      presented and discussed here.

PMID- 18822292
TI  - Evaluation of logistic and polynomial models for fitting sandwich-ELISA
      calibration curves.
AB  - Appropriately modeled calibration curves are important for accurately estimating
      the concentrations of proteins in samples evaluated in sandwich-format enzyme
      linked immunosorbent assay (ELISA). Calibration curves are commonly fit using
      polynomial or logistic models. We compared the fit of a quadratic, cubic and 4
      parameter logistic model for highly-replicated calibration curves across seven
      assays used for quantifying transgenic proteins in commercial crops. Results
      indicate that it is typically undesirable to include zero-concentration data when
      modeling these curves over the quantitative range, and simple polynomial models
      are typically preferable to the commonly recommended 4-parameter logistic model.
      These results are applicable to assays where precision constraints preclude
      interpolating results from the flat portions of the calibration curve, and it is
      under these conditions that the moderate improvements in accuracy described here
      will have impact.

PMID- 18822293
TI  - Hygropreference and brood care in the honeybee (Apis mellifera).
AB  - Terrestrial organisms need to limit evaporation from their bodies in order to
      maintain a homeostatic water balance. Owing to a large surface to volume ratio,
      arthropods are particularly susceptible to desiccation and have evolved
      behavioural and physiological mechanisms to conserve water. In social insects,
      water balance is also affected by the interactions between nestmates and by the
      architecture of the nest. For honeybees, humidity is particularly important for
      the brood because it affects the hatching success of eggs and because, unlike
      ants, honeybees cannot relocate their brood to parts of the nest with more
      favourable humidity. To advance the understanding of the water economy in
      honeybee nests, we investigated whether workers exhibit a hygropreference when
      exposed to a gradient of 24-90% relative humidity (RH) and whether the expression
      of this preference and their behaviour is affected by the presence of brood. The
      results show that young honeybee workers in the absence of brood exhibit a weak
      hygropreference for approximately 75% RH. When brood is present the expression of
      this preference is further weakened, suggesting that workers tend to the brood by
      distributing evenly in the gradient. In addition, fanning behaviour is shown to
      be triggered by an increase in humidity above the preferred level but not by a
      decrease. Our results suggest that humidity in honeybee colonies is actively
      controlled by workers.

PMID- 18822294
TI  - Spectral sensitivity and wing colors of Narathura and Panchala species.
AB  - Spectral sensitivity and wing colors were compared among three species of
      lycaenid butterflies, Panchala ganesa, Narathura bazalus and Narathura japonica.
      Spectral sensitivity was examined by the ERG method using an integrating sphere
      which could stimulate the whole surface of the compound eye. Wing colors were
      measured using a spectrophotometer. All three species examined were sensitive to
      a broad wavelength range, from UV to red light, with the primary peak in the
      shorter wavelength region. Slight peak shifts were observed among the studied
      species; species with wings reflecting shorter wavelength light tended to be
      sensitive to shorter wavelength lights.

PMID- 18822295
TI  - Artificial binding proteins (Affitins) as probes for conformational changes in
      secretin PulD.
AB  - The DNA-binding protein Sac7d was previously modified to bind with high affinity
      to the N domain of the outer membrane secretin PulD from the bacterium Klebsiella
      oxytoca. Here, we show that binding of the Sac7d derivatives (affitins) to PulD
      is sensitive to conformational changes caused by denaturant and by the
      zwitterionic detergent Zwittergent 3-14 routinely used to extract secretins from
      outer membranes. This sensitivity to the conformational state of PulD allowed us
      to use the affitins as probes for the native structure of PulD and to devise
      protocols for examining in vitro synthesized protein in nonionic detergent and
      for the affinity purification of native PulD using affitins as ligands. When
      fused to periplasmic PhoA, three affitins inhibited PulD multimerization in vivo
      and caused loss of function. In two cases, this was likely to be due to
      dimerization of the affitin by the bound PhoA, as the effect was absent when the
      affitins were fused to monomeric MalE. In the third case, the MalE and PhoA
      moieties probably interfered sterically with PulD protomer interactions and,
      thereby, inhibited multimerization. None of the affitins tested interacted with
      PulD at sites of protomer interaction or blocked the secretin channel through
      which exoproteins cross the outer membrane in the Type II secretion pathway of
      which PulD is a key component.

PMID- 18822296
TI  - The expression level of the chromatin-associated HMGB1 protein influences growth,
      stress tolerance, and transcriptome in Arabidopsis.
AB  - High mobility group (HMG) proteins of the HMGB family are small and relatively
      abundant chromatin-associated proteins. As architectural factors, the HMGB
      proteins are involved in the regulation of transcription and other DNA-dependent
      processes. We have examined Arabidopsis mutant plants lacking the HMGB1 protein,
      which is a typical representative of the plant HMGB family. In addition, our
      analyses included transgenic plants overexpressing HMGB1 and mutant plants that
      were transformed with the HMGB1 genomic region (complementation plants), as well
      as control plants. Both the absence and overexpression of HMGB1 caused shorter
      primary roots and affected the sensitivity towards the genotoxic agent methyl
      methanesulfonate. The overexpression of HMGB1 decreased the seed germination rate
      in the presence of elevated concentrations of NaCl. The complementation plants
      that expressed HMGB1 at wild-type levels did not show phenotypic differences
      compared to the control plants. Transcript profiling by microarray hybridization
      revealed that a remarkably large number of genes were differentially expressed
      (up- and down-regulated) in plants lacking HMGB1 compared to control plants.
      Among the down-regulated genes, the gene ontology category of stress-responsive
      genes was overrepresented. Neither microscopic analyses nor micrococcal nuclease
      digestion experiments revealed notable differences in overall chromatin
      structure, when comparing chromatin from HMGB1-deficient and control plants.
      Collectively, our results show that despite the presence of several other HMGB
      proteins, the lack and overexpression of HMGB1 affect certain aspects of plant
      growth and stress tolerance and it has a marked impact on the transcriptome,
      suggesting that HMGB1 has (partially) specialized functions in Arabidopsis.

PMID- 18822297
TI  - Electrostatics in the ribosomal tunnel modulate chain elongation rates.
AB  - Electrostatic potentials along the ribosomal exit tunnel are nonuniform and
      negative. The significance of electrostatics in the tunnel remains relatively
      uninvestigated, yet they are likely to play a role in translation and secondary
      folding of nascent peptides. To probe the role of nascent peptide charges in
      ribosome function, we used a molecular tape measure that was engineered to
      contain different numbers of charged amino acids localized to known regions of
      the tunnel and measured chain elongation rates. Positively charged arginine or
      lysine sequences produce transient arrest (pausing) before the nascent peptide is
      fully elongated. The rate of conversion from transiently arrested to full-length
      nascent peptide is faster for peptides containing neutral or negatively charged
      residues than for those containing positively charged residues. We provide
      experimental evidence that extraribosomal mechanisms do not account for this
      charge-specific pausing. We conclude that pausing is due to charge-specific
      interactions between the tunnel and the nascent peptide.

PMID- 18822298
TI  - Genetic and structural characterization of an L201P global suppressor
      substitution in TEM-1 beta-lactamase.
AB  - TEM-1 beta-lactamase confers bacterial resistance to penicillin antibiotics and
      has acquired mutations that permit the enzyme to hydrolyze extended-spectrum
      cephalosporins or to avoid inactivation by beta-lactamase inhibitors. However,
      many of these substitutions have been shown to reduce activity against penicillin
      antibiotics and/or result in loss of stability for the enzyme. In order to gain
      more information concerning the tradeoffs associated with active site
      substitutions, a genetic selection was used to find second site mutations that
      partially restore ampicillin resistance levels conferred by an R244A active site
      TEM-1 beta-lactamase mutant. An L201P substitution distant from the active site
      that enhanced ampicillin resistance levels and increased protein expression
      levels of the R244A TEM-1 mutant was identified. The L201P substitution also
      increases the ampicillin resistance levels and restores expression levels of a
      poorly expressed TEM-1 mutant with a core-disrupting substitution. In vitro
      thermal denaturation of purified protein indicated that the L201P mutation
      increases the T(m) value of the TEM-1 enzyme. The X-ray structure of the L201P
      TEM-1 mutant was determined to gain insight into the increase in enzyme
      stability. The proline substitution occurs at the N-terminus of an alpha-helix
      and may stabilize the enzyme by reducing the helix dipole, as well as by lowering
      the conformational entropy cost of folding due to the reduced number of
      conformations available in the unfolded state. Collectively, the data suggest
      that L201P promotes tolerance of some deleterious TEM-1 mutations by enhancing
      the protein stability of these mutants.

PMID- 18822299
TI  - Bag-1M is a component of the in vivo DNA-glucocorticoid receptor complex at
      hormone-regulated promoter.
AB  - Molecular chaperones and cochaperones are known to participate in nuclear
      receptor-mediated gene expression in addition to providing the appropriate
      conformation for hormone binding. It has been reported that Bag-1M (Bcl-2
      associated athanogene 1M) downregulates the transactivation function of the
      glucocorticoid receptor (GR). Here, we demonstrate that Bag-1M downregulates the
      glucocorticoid function via binding to distinct amino acid sequences in the hinge
      region of the GR. In cells expressing the human metallothionein IIa gene,
      overexpression of Bag-1M resulted in an in vivo dissociation of the DNA-receptor
      complex and a decrease in glucocorticoid-mediated transcription, indicating that
      this cochaperone acts as a negative regulator of GR action. In Bag-1M-expressing
      cells, this cochaperone is recruited with the GR to genomic hormone response
      element following glucocorticoid treatment. In line with this, small interfering
      RNA knockdown of the cellular level of Bag-1M enhanced DNA binding by the GR,
      resulting in a robust increase in transcriptional activity. These findings
      identify a regulatory mechanism, downstream of hormone binding, used by Bag-1M
      for attenuating GR action in response to its changing cellular levels.

PMID- 18822300
TI  - A note on plating efficiency in fluctuation experiments.
AB  - In estimating mutation rates using the Luria-Delbruck experimental protocol, it
      is often assumed that all mutant cells survive the plating procedure to form
      visible mutant colonies. This assumption of perfect plating efficiency may not
      hold in certain circumstances, but none of the existing estimation methods that
      adjust for plating efficiency is strictly based on the likelihood principle. To
      ameliorate this situation, we propose likelihood based algorithms for computing
      point and interval estimates of mutation rates.

PMID- 18822301
TI  - Arsenic trioxide mutational spectrum analysis in the mouse lymphoma assay.
AB  - It has been well documented that long-term exposure to inorganic arsenic induces
      cancers and vascular diseases in a dose-response relationship. Nevertheless,
      arsenic has also demonstrated to have anticancer activity; thus, arsenic trioxide
      (ATO, As2O3) is an inorganic trivalent arsenic form, currently used in the
      treatment against acute promyelocytic leukaemia (APL). The open discussion about
      how arsenic compounds induce genotoxic damage has moved us to evaluate the
      mutational spectrum induced by ATO in mouse lymphoma cells. Thus, 49 Tk-/- mutant
      colonies obtained in the mouse lymphoma assay (MLA), after treatments lasting for
      4h with 10microM ATO, and 49 spontaneous mutant colonies from independent
      untreated cultures, were used to analyse and to characterise the mutational
      spectrum induced by this arsenic compound, to understand its mechanism of action.
      RT-PCR analysis of Tk cDNA and PCR amplifications of eight selected
      microsatellite sequences, located on chromosome 11, were used to carry out this
      screening. Our results show that, in mouse lymphoma cells, ATO is a strong
      clastogenic compound inducing large deletions, at chromosomal level, covering the
      Tk gene, as well as other regions of chromosome 11.

PMID- 18822302
TI  - Functional analysis of HNPCC-related missense mutations in MSH2.
AB  - Hereditary nonpolyposis colorectal cancer (HNPCC) is associated with germline
      mutations in the human DNA mismatch repair (MMR) genes, most frequently MSH2 and
      MLH1. The majority of HNPCC mutations cause truncations and thus loss of function
      of the affected polypeptide. However, a significant proportion of MMR mutations
      found in HNPCC patients are single amino acid substitutions and the functional
      consequences of many of these mutations in DNA repair are unclear. We have
      examined the consequences of seven MSH2 missense mutations found in HNPCC
      families by testing the MSH2 mutant proteins in functional assays as well as by
      generating equivalent missense mutations in Escherichia coli MutS and analyzing
      the phenotypes of these mutants. Here we show that two mutant proteins, MSH2
      P622L and MSH2-C697F confer multiple biochemical defects, namely in mismatch
      binding, in vivo interaction with MSH6 and EXO1, and in nuclear localization in
      the cell. Mutation G674R, located in the ATP-binding region of MSH2, appears to
      confer resistance to ATP-dependent mismatch release. Mutations D167H and H639R
      show reduced mismatch binding. Results of in vivo experiments in E. coli with
      MutS mutants show that one additional mutant, equivalent of MSH2-A834T that do
      not show any defects in MSH2 assays, is repair deficient. In conclusion, all
      mutant proteins (except for MSH2-A305T) have defects; either in mismatch binding,
      ATP-release, mismatch repair activity, subcellular localization or protein
      protein interactions.

PMID- 18822303
TI  - Augmentation of antipsychotic-induced neurochemical changes by the NK3 receptor
      antagonist talnetant (SB-223412).
AB  - Neurokinin-3 (NK(3)) receptor distribution and its modulatory influence on
      dopaminergic and noradrenergic neurotransmission have lead to the hypothesis that
      NK(3) receptor antagonists may be a valid target to ameliorate the symptomatology
      of schizophrenia. This hypothesis has gained some clinical support as the
      selective NK(3) receptor antagonist osanetant has shown efficacy in schizophrenic
      patients. Talnetant (SB-223412) is a potent and selective NK(3) receptor
      antagonist able to modulate monoaminergic neurotransmission in both cortical and
      subcortical brain structures. Here we have used in vivo microdialysis to
      investigate the adjunctive effects of talnetant (10 and 30 mg/kg; i.p.) on
      typical (i.e. haloperidol, 0.3 and 1 mg/kg; i.p.) and atypical (i.e. risperidone,
      0.3 and 1 mg/kg; i.p.) antipsychotic drug-induced changes in monoaminergic
      neurotransmission in forebrain structures of the guinea pig. As seen previously
      talnetant, produced a dose dependent increase in extracellular levels of both
      dopamine (DA) and norepinephrine (NE) in both prefrontal cortex (PFC) and
      hippocampus in a similar manner to the atypical risperidone. Combination studies
      revealed an additive effect of talnetant on risperidone-induced changes in both
      NE and DA levels in the PFC but not the hippocampus. Furthermore, addition of
      talnetant converted the neurochemical profile of the typical antipsychotic,
      haloperidol, to a profile more akin to that induced by an atypical antipsychotic.
      These data suggest that addition of talnetant to antipsychotic drugs may
      facilitate monoaminergic neurotransmission and hence potentially improve their
      clinical efficacy.

PMID- 18822304
TI  - A hand in the blindsight paradox: a subcortical pathway?

PMID- 18822305
TI  - Koniocellular projections and hand-assisted blindsight.

PMID- 18822306
TI  - Evaluating the role of prefrontal and parietal cortices in memory-guided response
      with repetitive transcranial magnetic stimulation.
AB  - The dorsolateral prefrontal cortex (dlPFC) plays an important role in working
      memory, including the control of memory-guided response. In this study, with 24
      subjects, we used high frequency repetitive transcranial magnetic stimulation
      (rTMS) to evaluate the role of the dlPFC in memory-guided response to two
      different types of spatial working memory tasks: one requiring a recognition
      decision about a probe stimulus (operationalized with a yes/no button press),
      another requiring direct recall of the memory stimulus by moving a cursor to the
      remembered location. In half the trials, randomly distributed, rTMS was applied
      to the dlPFC and in a separate session, the superior parietal lobule (SPL), a
      brain area implicated in spatial working memory storage. A 10-Hz (3s, 110% of
      motor threshold) train of TMS was delivered at the onset of the response period.
      We found that only dlPFC rTMS significantly affected performance, with rTMS of
      right dlPFC decreasing accuracy on delayed-recall trials, and rTMS of left and
      right dlPFC decreasing and enhancing accuracy, respectively, on delayed
      recognition trials. These findings confirm that the dlPFC plays an important role
      in memory-guided response, and suggest that the nature of this role varies
      depending on the processes required for making a response.

PMID- 18822307
TI  - Motion integration deficits are independent of magnocellular impairment in
      Parkinson's disease.
AB  - Motion processing involves multiple hierarchical steps, from the magnocellular
      pathway, sensitive to high temporal frequency modulations, to subsequent motion
      integration within the visual cortical dorsal stream. We have tested whether
      motion integration deficits in mild Parkinson disease (PD) can be explained by
      visual deficits in earlier processing nodes. Contrast sensitivity deficits in the
      magnocellular pathway, were compared with speed discrimination of local dots
      moving in random directions, speed and direction discrimination of moving
      surfaces and motion integration as measured by 2D coherence thresholds (n=27). We
      have found that low-level magnocellular impairment in PD does not explain
      deficits in subsequent steps in motion processing. High-level performance was
      abnormal in particular for tasks requiring perception of coherently moving
      surfaces. Motion coherence deficits were predictive of visuomotor impairment,
      corroborating a previous magnetic stimulation study in normal subjects. We
      conclude that dorsal stream deficits in PD have a high-level visual cortical
      basis independent of low-level magnocellular damage.

PMID- 18822308
TI  - Improved sensorimotor adaptation after exhaustive exercise is accompanied by
      altered brain activity.
AB  - Acute exercise has been shown to exhibit different effects on human sensorimotor
      behavior; however, the causes and mechanisms of the responses are often not
      clear. The primary aim of the present study was to determine the effects of
      incremental running until exhaustion on sensorimotor performance and adaptation
      in a tracking task. Subjects were randomly assigned to a running group (RG), a
      tracking group (TG), or a running followed by tracking group (RTG), with 10
      subjects assigned to each group. Treadmill running velocity was initially set at
      2.0 m s(-1), increasing by 0.5 m s(-1) every 5 min until exhaustion. Tracking
      consisted of 35 episodes (each 40 s) where the subjects' task was to track a
      visual target on a computer screen while the visual feedback was veridical
      (performance) or left-right reversed (adaptation). Resting
      electroencephalographic (EEG) activity was recorded before and after each
      experimental condition (running, tracking, rest). Tracking performance and the
      final amount of adaptation did not differ between groups. However, task
      adaptation was significantly faster in RTG compared to TG. In addition, increased
      alpha and beta power were observed following tracking in TG but not RTG although
      exhaustive running failed to induce significant changes in these frequency bands.
      Our results suggest that exhaustive running can facilitate adaptation processes
      in a manual tracking task. Attenuated cortical activation following tracking in
      the exercise condition was interpreted to indicate cortical efficiency and
      exercise-induced facilitation of selective central processes during actual task
      demands.

PMID- 18822309
TI  - Developmental plasticity of human reproductive development: effects of early
      family environment in modern-day France.
AB  - In a first study, we investigated how the absence of a father and the presence of
      a stepfather during early childhood affected physiological and behavioral traits
      related to reproductive development (such as age of menarche, age of first sexual
      intercourse and number of sexual partners) in a large sample set of male and
      female French university students. We evaluated which ages were sensitive to
      modifications in the family composition and found that menarche occurred earlier
      when the father was absent, particularly when the child was between 0 and 5 years
      of age. Father absence during early adolescence was associated with a younger age
      at first sexual intercourse and an increased number of sexual partners, for both
      sexes. The presence of a stepfather during this period further advanced the age
      of first sexual intercourse. We also measured testosterone levels in both sexes
      and analyzed their association with parental separation, and found that young
      women with separated parents had significantly higher afternoon levels of
      testosterone. In a second study, we analyzed direct fitness measures (such as
      number of children and grandchildren) in a large sample of French workers and
      found that parental separation during childhood was not associated with fitness
      variation. We discuss whether the reproductive outcomes of individuals having
      experienced modifications in the early family environment are the expression of
      costs or adaptive strategies.

PMID- 18822310
TI  - Arsenic trioxide phosphorylates c-Fos to transactivate p21(WAF1/CIP1) expression.
AB  - An infamous poison, arsenic also has been used as a drug for nearly 2400 years;
      in recently years, arsenic has been effective in the treatment of acute
      promyelocytic leukemia. Increasing evidence suggests that opposite effects of
      arsenic trioxide (ATO) on tumors depend on its concentrations. For this reason,
      the mechanisms of action of the drug should be elucidated, and it should be used
      therapeutically only with extreme caution. Previously, we demonstrated the
      opposing effects of ERK1/2 and JNK on p21(WAF1/CIP1) (p21) expression in response
      to ATO in A431 cells. In addition, JNK phosphorylates c-Jun (Ser(63/73)) to
      recruit TGIF/HDAC1 to suppress p21 gene expression. Presently, we demonstrated
      that a high concentration of ATO sustains ERK1/2 phosphorylation, and increases c
      Fos biosynthesis and stability, which enhances p21 gene expression. Using site
      directed mutagenesis, a DNA affinity precipitation assay, and functional assays,
      we demonstrated that phosphorylation of the C-terminus of c-Fos (Thr(232),
      Thr(325), Thr(331), and Ser(374)) plays an important role in its binding to the
      p21 promoter, and in conjunction with N-terminus phosphorylation of c-Fos
      (Ser(70)) to transactivate p21 promoter expression. In conclusion, a high
      concentration of ATO can sustain ERK1/2 activation to enhance c-Fos expression,
      then dimerize with dephosphorylated c-Jun (Ser(63/73)) and recruit p300/CBP to
      the Sp1 sites (-84/-64) to activate p21 gene expression in A431 cells.

PMID- 18822311
TI  - Inhalation carcinogenicity study with nickel metal powder in Wistar rats.
AB  - Epidemiological studies of nickel refinery workers have demonstrated an
      association between increased respiratory cancer risk and exposure to certain
      nickel compounds (later confirmed in animal studies). However, the lack of an
      association found in epidemiological analyses for nickel metal remained
      unconfirmed for lack of robust animal inhalation studies. In the present study,
      Wistar rats were exposed by whole-body inhalation to 0, 0.1, 0.4, and 1.0 mg
      Ni/m(3) nickel metal powder (MMAD=1.8 microm, GSD=2.4 microm) for 6 h/day, 5
      days/week for up to 24 months. A subsequent six-month period without exposures
      preceded the final euthanasia. High mortality among rats exposed to 1.0 mg
      Ni/m(3) nickel metal resulted in the earlier termination of exposures in this
      group. The exposure level of 0.4 mg Ni/m(3) was established as the MTD for the
      study. Lung alterations associated with nickel metal exposure included alveolar
      proteinosis, alveolar histiocytosis, chronic inflammation, and bronchiolar
      alveolar hyperplasia. No increased incidence of neoplasm of the respiratory tract
      was observed. Adrenal gland pheochromocytomas (benign and malignant) in males and
      combined cortical adenomas/carcinomas in females were induced in a dose-dependent
      manner by the nickel metal exposure. The incidence of pheochromocytomas was
      statistically increased in the 0.4 mg Ni/m(3) male group. Pheochromocytomas
      appear to be secondary to the lung toxicity associated with the exposure rather
      than being related to a direct nickel effect on the adrenal glands. The incidence
      of cortical tumors among 0.4 mg Ni/m(3) females, although statistically higher
      compared to the concurrent controls, falls within the historical control range;
      therefore, in the present study, this tumor is of uncertain relationship to
      nickel metal exposure. The lack of respiratory tumors in the present animal study
      is consistent with the findings of the epidemiological studies.

PMID- 18822312
TI  - The immunogenic properties of protozoan glycosylphosphatidylinositols in the
      mosquito Anopheles gambiae.
AB  - In contrast to humans, mosquitoes do not have an adaptive immune response to deal
      with pathogens, and therefore must rely on their innate immune system to deal
      with invaders. This facilitates the recognition of different microbes on the
      basis of surface components or antigens. Such antigens have been identified in
      various types of microbe such as bacteria and fungi, yet none has been identified
      in the genus protozoa, which includes pathogens such as the malaria parasite,
      Plasmodium falciparum and Toxoplasma gondii. This study allowed us to test the
      antigenic properties of protozoan glycosylphosphatidylinositol (GPI) on the
      mosquito immune system. We found that both P. falciparum GPI and T. gondii GPI
      induce the strong expression of several antimicrobial peptides following
      ingestion, and that as a result of the immune response against the GPIs, the
      number of eggs produced by the mosquito is reduced dramatically. Such effects
      have been associated with malaria infected mosquitoes, but never associated with
      a Plasmodium specific antigen. This study demonstrates that protozoan GPIs can be
      considered as protozoan specific immune elicitors in mosquitoes, and that P.
      falciparum GPI plays a critical role in the malaria parasite manipulation of the
      mosquito vector to facilitate its transmission.

PMID- 18822313
TI  - Models of response inhibition in the stop-signal and stop-change paradigms.
AB  - The stop-signal paradigm is very useful for the study of response inhibition.
      Stop-signal performance is typically described as a race between a go process,
      triggered by a go stimulus, and a stop process, triggered by the stop signal.
      Response inhibition depends on the relative finishing time of these two
      processes. Numerous studies have shown that the independent horse-race model of
      Logan and Cowan [Logan, G.D., Cowan, W.B., 1984. On the ability to inhibit
      thought and action: a theory of an act of control. Psychological Review 91, 295
      327] accounts for the data very well. In the present article, we review the
      independent horse-race model and related models, such as the interactive horse
      race model [Boucher, L., Palmeri, T.J., Logan, G.D., Schall, J.D., 2007.
      Inhibitory control in mind and brain: an interactive race model of countermanding
      saccades. Psychological Review 114, 376-397]. We present evidence that favors the
      independent horse-race model but also some evidence that challenges the model. We
      end with a discussion of recent models that elaborate the role of a stop process
      in inhibiting a response.

PMID- 18822315
TI  - Independent positioning of microelectrodes for multisite recordings in vitro.
AB  - A robust and easy to handle, inexpensive multisite recording system is described
      which allows independent positioning of several microelectrodes with high
      precision axial movement of each electrode. The basic units of the system are a
      manually operated manipulator for left-right and up-down movement and a
      micrometer for positioning in the direction of the micrometer axis. The
      micrometer is actuated with a DC-motor operated by a stand-alone controller
      module allowing for remote control of the motor in either step mode or continuous
      mode. The multisite recording system has been proven to allow stable simultaneous
      recordings of single unit and population activities, extracellular ion
      concentrations and intracellular potentials in organotypic hippocampal slice
      cultures (OHSCs) of rat.

PMID- 18822314
TI  - Toll-like receptors in neurodegeneration.
AB  - The key roles of toll-like receptors (TLRs) as mediators of the detection and
      responses of immune cells to invading pathogens are well known. There are at
      least 13 mammalian TLRs which are integral membrane proteins with a leucine-rich
      extracellular domain and a cytoplasmic domain similar to that of the interleukin
      1 receptor which initiates downstream signaling through kinases to activate
      transcription factors such as AP-1 and NFkappaB. TLRs are activated in glial
      cells (microglia, astrocytes and oligodendrocytes) and lymphocytes that
      infiltrate the nervous system in response to inflammation caused by infectious
      agents, tissue injury or autoimmune conditions. By inducing the production of pro
      inflammatory cytokines and cell adhesion molecules in immune cells, TLRs may
      indirectly damage neurons in conditions such as ischemic stroke and multiple
      sclerosis. Recent findings suggest that neurons also express a subset of TLRs and
      that their activation promotes neuronal degeneration in experimental models of
      stroke and Alzheimer's disease. TLRs may also play roles in regulating the
      processes of neurogenesis and neurite outgrowth, suggesting roles in neuronal
      plasticity. A better understanding of the molecular and cellular biology of TLRs
      in the normal and diseased nervous system, may lead to novel approaches for
      preventing neuronal degeneration and promoting recovery of function in an array
      of neurodegenerative conditions.

PMID- 18822316
TI  - Transfection of adult canine Schwann cells and olfactory ensheathing cells at
      early and late passage with human TERT differentially affects growth factor
      responsiveness and in vitro growth.
AB  - Adult canine Schwann cells and olfactory ensheathing cells (OECs) are closely
      related cell types that are considered attractive candidates for translational
      studies of neural repair. To establish a reliable cell source by comparing the in
      vitro properties of immortalized Schwann cells and OECs for transplantation
      purposes, we transfected both cell types with human telomerase reverse
      transcriptase (hTERT). Ectopic hTERT expression has been shown to induce
      immortalization of various cell types without substantial alterations of their
      phenotypes. Schwann cells and OECs were isolated from adult dogs, transfected
      with hTERT at early (P4) and late passage (P26), characterized regarding in vitro
      proliferation, antigenic expression and senescence-associated genes in the
      presence and absence of fibroblast growth factor-2 (FGF-2). Ectopic hTERT
      expression in late passage glia treated with but not without FGF-2 prevented the
      decline in proliferation observed in non-transfected cells. Immortalization did
      not alter p75(NTR) and GFAP but O4 and A2B5 expression. Contrary to this, early
      passage hTERT transfection significantly reduced proliferation independent of FGF
      2 and lowered expression of O4 and GFAP in both cell types. Transfection did not
      alter mRNA expression of senescence-associated genes such as p53 and p16. No
      substantial differences were found between Schwann cells and OECs underscoring
      the close relationship of both cell types. Taken together, we established a
      stable source of adult canine Schwann cells and OECs and demonstrated that the
      effects of hTERT expression on in vitro growth and growth factor responsiveness
      depend on the replicative age.

PMID- 18822317
TI  - Pathogenic anti-DNA antibodies modulate gene expression in mesangial cells:
      involvement of HMGB1 in anti-DNA antibody-induced renal injury.
AB  - Although anti-DNA antibodies have been decisively linked to the pathogenesis of
      lupus nephritis, the mechanisms have not been conclusively determined. Recently,
      we reported that anti-DNA antibodies may contribute to kidney damage by
      upregulation of proinflammatory genes in mesangial cells (MC), a process
      involving both Fc receptor-dependent and independent pathways. In investigating
      the mechanism by which pathogenic anti-DNA antibodies modulate gene expression in
      MC, we found that the pathogenic anti-DNA antibody 1A3F bound to high mobility
      group binding protein 1 (HMGB1), an endogenous ligand for TLR2/4 and RAGE
      (receptor for advanced glycation end products). Interestingly, HMGB1 treatment of
      MC induced a similar pattern of genes as stimulation with 1A3F. Furthermore,
      HMGB1 and 1A3F exhibited a synergistic proinflammatory effect in the kidney,
      where increased expression of HMGB1 was found in lupus patients but not in
      patients with other types of renal disease. TLR2/Fc and RAGE/Fc inhibited the
      proinflammatory effects of 1A3F on MC. Finally, we found enhanced susceptibility
      of lupus prone MRL-lpr/lpr (MRL/lpr) as compared to normal BALB/c derived MC to
      pathogenic anti-DNA antibody and LPS stimulation (in particular enhanced
      chemokine synthesis), in addition to significantly increased expression of TLR4.
      Our results suggest that gene upregulation in MC induced by nephritogenic anti
      DNA antibodies is TLR2/4 and RAGE-dependent. Finally, HMGB1 may act as a
      proinflammatory mediator in antibody-induced kidney damage in systemic lupus
      erythematosus (SLE).

PMID- 18822318
TI  - Effects of rat sex differences and lighting on locomotor exploration of a
      circular open field with free-standing central corners and without peripheral
      walls.
AB  - A typical open field consists of a square enclosure, bounded by four straight
      walls joined by identical corners. For decades behavioral researchers have used
      the open center and more sheltered perimeter of such fields to examine the
      effects of drugs, sex differences, and illumination on the behavioral expression
      of fear and anxiety. The present study "reversed" the relative security of the
      center and periphery of a circular field to re-examine the functional relation of
      open field behavior to experience, sex differences and lighting. Across six daily
      exposures, males in both the light and dark rapidly increased their preference
      for the center. Females in the light developed a similar pattern, though more
      slowly; females in the dark continued to spend the great majority of their time
      in the open periphery, including the edge of the field. The behavior of all
      groups, but especially the dark females, strongly supports the continued
      importance of environmental assessment in open field behavior.

PMID- 18822319
TI  - Drug-seeking behavior in an invertebrate system: evidence of morphine-induced
      reward, extinction and reinstatement in crayfish.
AB  - Several lines of evidence suggest that exploring the neurochemical basis of
      reward in invertebrate species may provide clues for the fundamental behavioral
      and neurobiology underpinnings of drug addiction. How the presence of drug
      sensitive reward relates to a decrease in drug-seeking behavior and reinstatement
      of drug-seeking behavior in invertebrate systems is not known. The present study
      of a conditioned place preference (CPP) paradigm in crayfish (Orconectes
      rusticus) explores morphine-induced reward, extinction and reinstatement.
      Repeated intra-circulatory infusions of 2.5 microg/g, 5.0 microg/g and 10.0
      microg/g doses of morphine over 5 days serve as a reward when paired with a
      distinct visual or tactile environment. Morphine-induced CPP was extinguished
      after repeated saline injections for 5 days in the previously morphine-paired
      compartment. After the previously established CPP had been eliminated during the
      extinction phase, morphine-experienced crayfish were challenged with 2.5
      microg/g, 5.0 microg/g and 10.0 microg/g, respectively. The priming injections of
      morphine reinstated CPP in all training doses, suggesting that morphine-induced
      CPP is unrelenting, and that with time, it can be reinstated by morphine
      following extinction in an invertebrate model just like in mammals. Together with
      other recent studies, this work demonstrates the advantage of using crayfish as
      an invertebrate animal model to investigate the basic biological processes that
      underline exposure to mammalian drugs of abuse.

PMID- 18822320
TI  - Extracellular superoxide released from mitochondria mediates mast cell death by
      advanced glycation end products.
AB  - Advanced glycation end products (AGEs) accumulate during aging and to higher
      extents under pathological conditions such as diabetes. Since we previously
      showed that mast cells expressed the AGE-binding protein, receptor for AGEs
      (RAGE) on their cell surface, we examined whether AGE affected mast cell
      survival. Herein, we demonstrate that mast cells undergo apoptosis in response to
      AGE. Glycated albumin (GA), an AGE, but not stimulation with the high-affinity
      IgE receptor (FcepsilonRI), can induce mast cell death, as measured by annexin
      V/propidium iodide double-staining. GA (> or =0.1 mg/ml) exhibited this pro
      apoptotic activity in a concentration-dependent manner. GA and FcepsilonRI
      stimulation increased the cytosolic Ca(2+) levels to a similar extent, whereas
      GA, but not FcepsilonRI stimulation, caused mitochondrial Ca(2+) overload and
      membrane potential collapse, resulting in mitochondrial integrity disruption,
      cytochrome c release and caspase-3/7 activation. In addition, GA, but not
      FcepsilonRI stimulation, induced extracellular release of superoxide from
      mitochondria, and this release played a key role in the disruption of Ca(2+)
      homeostasis. Knockdown of RAGE expression using small interfering RNA abolished
      GA-induced apoptosis, mitochondrial Ca(2+) overload, and superoxide release,
      demonstrating that RAGE mediates the GA-induced mitochondrial death pathway. AGE
      induced mast cell apoptosis may contribute to the immunocompromised and
      inflammatory conditions.

PMID- 18822321
TI  - A novel and rapid method for determining integration frequency catalyzed by
      integron integrase intI1.
AB  - We developed a faster and more convenient method to determine integration
      frequency mediated by integron integrase intI1. This method based on real-time
      fluorescent quantitative PCR. By using this method, we revealed that the
      integration frequency of aadA2 gene cassette was 1.87x10(-4) when integrase intI1
      was present, and the background frequency was less than 5.23x10(-8) without
      integrase intI1.

PMID- 18822322
TI  - Involvement of the left inferior frontal gyrus in predictive inference making.
AB  - Although predictive inference in reading has been extensively investigated with
      behavioral paradigms, little is known about its neural substrates. Manipulating
      the likelihood that a particular event can be predicted from the content of a
      preceding three-sentence story, the present functional MRI study showed that the
      left inferior frontal gyrus (LIFG) and the right lingual gyrus were involved in
      predictive inference generation. It is suggested that the LIFG was responsible
      for the construction of predictive inference and the right lingual gyrus for
      integrating the constructed inference into a coherent text representation.
      Combined with previous research, the results provide brain imaging evidence
      consistent with predictions from the Schmalhofer et al. model (Discourse
      Processes, 33, 105-13, 2002) which intends to unify predictive inference and
      bridging inference in a single theoretical framework.

PMID- 18822323
TI  - Regenerating cellulose from ionic liquids for an accelerated enzymatic
      hydrolysis.
AB  - The efficient conversion of lignocellulosic materials into fuel ethanol has
      become a research priority in producing affordable and renewable energy. The
      pretreatment of lignocelluloses is known to be key to the fast enzymatic
      hydrolysis of cellulose. Recently, certain ionic liquids (ILs) were found capable
      of dissolving more than 10wt% cellulose. Preliminary investigations [Dadi, A.P.,
      Varanasi, S., Schall, C.A., 2006. Enhancement of cellulose saccharification
      kinetics using an ionic liquid pretreatment step. Biotechnol. Bioeng. 95, 904
      910; Liu, L., Chen, H., 2006. Enzymatic hydrolysis of cellulose materials treated
      with ionic liquid [BMIM]Cl. Chin. Sci. Bull. 51, 2432-2436; Dadi, A.P., Schall,
      C.A., Varanasi, S., 2007. Mitigation of cellulose recalcitrance to enzymatic
      hydrolysis by ionic liquid pretreatment. Appl. Biochem. Biotechnol. 137-140, 407
      421] suggest that celluloses regenerated from IL solutions are subject to faster
      saccharification than untreated substrates. These encouraging results offer the
      possibility of using ILs as alternative and non-volatile solvents for cellulose
      pretreatment. However, these studies are limited to two chloride-based ILs: (a) 1
      butyl-3-methylimidazolium chloride ([BMIM]Cl), which is a corrosive, toxic and
      extremely hygroscopic solid (m.p. approximately 70 degrees C), and (b) 1-allyl-3
      methylimidazolium chloride ([AMIM]Cl), which is viscous and has a reactive side
      chain. Therefore, more in-depth research involving other ILs is much needed to
      explore this promising pretreatment route. For this reason, we studied a number
      of chloride- and acetate-based ILs for cellulose regeneration, including several
      ILs newly developed in our laboratory. This will enable us to select inexpensive,
      efficient and environmentally benign solvents for processing cellulosic biomass.
      Our data confirm that all regenerated celluloses are less crystalline (58-75%
      lower) and more accessible to cellulase (>2 times) than untreated substrates. As
      a result, regenerated Avicel((R)) cellulose, filter paper and cotton were
      hydrolyzed 2-10 times faster than the respective untreated celluloses. A complete
      hydrolysis of Avicel((R)) cellulose could be achieved in 6h given the Trichoderma
      reesei cellulase/substrate ratio (w/w) of 3:20 at 50 degrees C. In addition, we
      observed that cellulase is more thermally stable (up to 60 degrees C) in the
      presence of regenerated cellulose. Furthermore, our systematic studies suggest
      that the presence of various ILs during the hydrolysis induced different degrees
      of cellulase inactivation. Therefore, a thorough removal of IL residues after
      cellulose regeneration is highly recommended, and a systematic investigation on
      this subject is much needed.

PMID- 18822324
TI  - Feruloyl esterase-catalysed synthesis of glycerol sinapate using ionic liquids
      mixtures.
AB  - The ability of a feruloyl esterase (AnFaeA), either in free or immobilised (cross
      linked enzyme aggregates) form, to catalyse the esterification of glycerol, a
      major by-product of the biodiesel industry, with sinapic acid was studied in four
      hexafluorophosphate anion-containing ionic liquids: ([Bmim][PF(6)],
      [Omim][PF(6)], [C(2)OHmim][PF(6)] and [C(5)O(2)mim][PF(6)]). Such ionic liquids
      are considered 'green' reaction systems. The synthetic reaction was optimised in
      [C(2)OHmim][PF(6)] and the highest conversion yield was 72.5+/-2.1%, while, at
      the same reaction conditions in [C(5)O(2)mim] [PF(6)], a similar conversion yield
      was obtained (76.7+/-1.5%). AnFaeA was active in its free and immobilised form,
      with the latter retaining a part of its synthetic activity after 5 consecutive
      24h-period reaction cycles. Sinapic acid was esterified to one of the primary
      hydroxyl groups of glycerol and retained, after esterification, 63.1+/-0.3% and
      89.5+/-1.1% of its antioxidant activity against low-density lipoprotein
      oxidation, when added at concentrations of 10 and 60muM, respectively, in the
      assay mixture.

PMID- 18822325
TI  - Molecular divergence of Grapevine virus A (GVA) variants associated with Shiraz
      disease in South Africa.
AB  - Shiraz disease (SD) is a highly destructive, insect-transmitted disease of noble
      grapevine cultivars, such as Shiraz and Merlot, in South Africa. Earlier studies
      revealed that, of the three molecular groups of GVA that were detected in local
      vineyards, variants of group II are closely associated with expression of this
      disease, and variants of group III are commonly present in GVA-infected SD
      negative plants [Goszczynski, D.E., 2007. Single-strand conformation polymorphism
      (SSCP), cloning and sequencing of Grapevine virus A (GVA) reveal a close
      association between related molecular variants of the virus and Shiraz disease in
      South Africa. Plant Pathol. 56, 755-762]. Among many GVA variants transmitted to
      Nicotiana benthamiana from various grapevines with different SD status, a variant
      of group II, referred to here as GTR1-2, was also isolated from a consistently SD
      negative Shiraz plant. The genome of this variant, along with 7 other GVA
      variants of the 3 molecular groups, including 4 variants of molecular group II
      associated with strong symptoms of SD, were sequenced. Results of comparative
      analysis of these genomes, with emphasis on differences between GTR1-2 and other
      variants of molecular group II, are presented. Among the many differences that
      were found, a 119 nt ORF2-related fragment was discovered within the native ORF2
      of a GVA variant, P163-M5. This variant was isolated from a grapevine used by
      local industry as a reliable positive control for SD in woody indexing. The
      variant induced symptoms in N. benthamina that were significantly more severe
      than those of other variants of molecular group II.

PMID- 18822326
TI  - Dynamic microPET technique: an in vivo GPS navigation tool.

PMID- 18822327
TI  - Novel double coated nanocapsules for intestinal delivery and enhanced oral
      bioavailability of tacrolimus, a P-gp substrate drug.
AB  - This study proposes a new concept of double coated nanocapsules to improve the
      oral bioavailability of a P-glycoprotein (P-gp) substrate drug, tacrolimus,
      without modulating the physiological activity of the P-gp pump. Tacrolimus was
      incorporated in nanocapsules with different ratios of two polymethacrylate
      polymers followed by microencapsulation of these nanocapsules within
      hydroxypropylmethylcellulose using a spray drying technique. The influence of
      different formulations of tacrolimus administered orally to rats and pigs on the
      drug's absorption was investigated. Histopathological studies were performed on
      rats to follow the nanocapsule path in enterocytes. The novel formulations that
      released mostly drug loaded nanocapsules in the intestine were shown to enhance
      markedly the oral absorption of tacrolimus. The relative oral bioavailability of
      tacrolimus was 4.9 and 2.45 fold compared to the commercial product in rats and
      pigs respectively. Although there is no direct evidence that intact nanocapsules
      internalized in the enterocytes, numerous small oil cores were detected within
      the enterocytes showing the potential of P-gp substrates incorporated in such
      nanocarriers to escape the efflux pump.

PMID- 18822328
TI  - Genetic variations of the chemokine scavenger receptor D6 are associated with
      liver inflammation in chronic hepatitis C.
AB  - Chronic hepatitis C (HCV) represents one of the most common chronic infections
      worldwide and is a major indication for liver transplantation. Liver inflammation
      is the main predictor of advanced fibrosis in HCV. Inflammatory cells are
      recruited to the liver by chemokines. Recently, a novel class of chemokine
      receptors has been characterized that lack signaling functions and are termed
      scavenger receptors. We determine here whether genetic variations of the
      scavenger receptor D6 contribute to the grade of liver inflammation in HCV. Four
      haplotype tagging single nucleotide polymorphisms (SNPs) were identified from
      HapMap that cover the genetic information of D6 (CCBP2). Among these SNPs,
      rs4683336 was associated with liver inflammation in qualitative (p = 0.003) and
      quantitative (p = 0.0086) genotype analysis. This association was confirmed in an
      independent cohort of HCV-infected patients (p = 0.006 for qualitative and p =
      0.0046 for quantitative analysis, respectively). Furthermore, the haplotype that
      is tagged by marker rs4683336 was significantly correlated with liver
      inflammation when compared with the most common D6 haplotype (p = 0.014). The
      importance of genetic variations in D6 was supported through the demonstration of
      an association of D6 mRNA expression with histologic inflammation in liver
      biopsies and a considerable range of D6 mRNA expression in isolated human
      hepatocytes. In conclusion, we demonstrate that variations in a chemokine
      scavenging receptor are significantly correlated with clinical inflammatory
      phenotypes such as HCV infection.

PMID- 18822329
TI  - Alloantigen-induced regulatory CD8+CD103+ T cells.
AB  - Regulatory T cells (Tregs) appear of great importance in the balance between
      alloreactivity and tolerance and subsets of both CD4(+) and CD8(+) T cells have
      been recognized to function as regulatory T cells after allogenic
      transplantation. Among the CD8(+) T-cell subsets, the CD103(+) cells were most
      recently identified as regulatory. In this review, we describe their phenotypical
      and functional properties, as well as their relevance for the alloimmune response
      in vivo. These CD8(+)CD103(+) Tregs are generated within mixed lymphocyte
      cultures (MLCs) and are elevated by additional transforming growth factor-beta.
      Interestingly, myeloid dendritic cells are the responsible cell type for
      induction of CD103(+) Tregs. Allostimulated CD8(+)CD103(+) Tregs display an
      antigen-experienced effector phenotype with limited effector functions such as
      cytotoxicity and interferon-gamma production and show a reduced proliferation
      capacity after restimulation. Beside this anergic phenotype, CD8(+)CD103(+) Tregs
      are able to suppress alloreactive effector T cells. Through intracellular
      cytokine staining and transwell assays, we showed that the mechanism of
      suppression is cytokine independent, but close cell-cell contact is required for
      suppression.

PMID- 18822330
TI  - Qa-1/HLA-E-restricted regulatory CD8+ T cells and self-nonself discrimination: an
      essay on peripheral T-cell regulation.
AB  - By discriminating self from nonself and controlling the magnitude and class of
      immune responses, the immune system mounts effective immunity against virtually
      any foreign antigens but avoids harmful immune responses to self. These are two
      equally important and related but distinct processes, which function in concert
      to ensure an optimal function of the immune system. Immunologically relevant
      clinical problems often occur because of failure of either process, especially
      the former. Currently, there is no unified conceptual framework to characterize
      the precise relationship between thymic negative selection and peripheral immune
      regulation, which is the basis for understanding self-non-self discrimination
      versus control of magnitude and class of immune responses. In this article, we
      explore a novel hypothesis of how the immune system discriminates self from
      nonself in the periphery during adaptive immunity. This hypothesis permits
      rational analysis of various seemingly unrelated biomedical problems inherent in
      immunologic disorders that cannot be uniformly interpreted by any currently
      existing paradigms. The proposed hypothesis is based on a unified conceptual
      framework of the "avidity model of peripheral T-cell regulation" that we
      originally proposed and tested, in both basic and clinical immunology, to
      understand how the immune system achieves self-nonself discrimination in the
      periphery.

PMID- 18822331
TI  - Efficient induction of oral tolerance by fusing cholera toxin B subunit with
      allergen-specific T-cell epitopes accumulated in rice seed.
AB  - Cholera toxin B (CTB) subunit is an efficient mucosal carrier molecule for
      induction of oral tolerance to antigens and allergens. Here, T-cell epitopes of
      Cry j 1 and Cry j 2, major allergens in Japanese cedar pollen, were expressed in
      rice seed as a fusion protein with either CTB or rice glutelin as a control.
      Feeding mice with rice seed containing CTB-fused T-cell epitopes suppressed
      allergen-specific IgE responses and pollen-induced clinical symptoms at 50-fold
      lower doses of T-cell epitopes than required when using control seed. Our
      findings present a novel potential strategy for immunotherapy of type-I allergy.

PMID- 18822332
TI  - Yersinia enterocolitica Yop mutants as oral live carrier vaccines.
AB  - Attenuated enteropathogenic yersiniae that translocate heterologous antigens into
      the cytosol of antigen presenting cells via their type three secretion system
      (TTSS) are considered promising candidates for the development of live oral
      vaccine carrier strains that induce CD8 T cell responses. Wild type Yersinia
      enterocolitica of serotype O:8 however efficiently suppresses the immune response
      of the host by translocating effector proteins called Yersinia outer proteins
      (Yops) into the cytosol of immune cells. We therefore tested immunogenicity,
      protective efficacy, and virulence ofyop mutants that translocate the model
      antigen Listeriolysin (LLO) of Listeria monocytogenes in a mouse model. A
      deltayopP mutant-based vaccine carrier strain induced the highest numbers of
      LLO91-99-specific CD8 T cells and effectively protected mice against a lethal
      challenge with Listeria whereas deltayopPT, deltayopPV(K42Q), and deltayopPO
      mutants of Y. enterocolitica induced fewer CD8 T cells and conferred only partial
      protection. The deltayopPH, deltayopPE, deltayopPM, and deltayopPQ mutants
      induced the weakest CD8 T cell response and did not significantly protect mice
      against Listeria presumably due to the strong attenuation of these strains in the
      mouse model. Even though a Y. enterocolitica strain WA-C(pTTSS), which
      translocated only LLO (but not Yops), induced superior MHC class I-restricted
      antigen presentation in DC compared to the deltayopP mutants in vitro, this
      strain was not able to significantly colonize mouse tissue or to induce CD8 T
      cell responses in vivo. The success in designing a Yersinia oral vaccine carrier
      is therefore dependent to a great extent on the subtle balance between
      immunogenicity and attenuation.

PMID- 18822333
TI  - Immunogenicity and protective efficacy of tuberculosis subunit vaccines
      expressing PPE44 (Rv2770c).
AB  - In this study we have evaluated the vaccine potential of a Mycobacterium
      tuberculosis antigen of the PPE protein family, namely PPE44 (Rv2770c). PPE44
      specific immune responses could be detected in mice acutely, chronically and
      latently infected with M. tuberculosis. Vaccination of mice with a plasmid DNA
      vaccine coding for PPE44 or recombinant PPE44 protein formulated in adjuvant
      generated strong cellular and humoral immune responses; immunodominant T cell
      epitopes were identified. Most importantly, vaccination of mice with both subunit
      vaccines followed by an intratracheal challenge with M. tuberculosis resulted in
      a protective efficacy comparable to the one afforded by BCG. Taken together these
      results indicate that PPE44 of M. tuberculosis is a protective antigen that could
      be included in novel subunit TB vaccines and that warrants further analysis.

PMID- 18822334
TI  - Development of a PIV-vectored RSV vaccine: preclinical evaluation of safety,
      toxicity, and enhanced disease and initial clinical testing in healthy adults.
AB  - MEDI-534 is a bivalent live attenuated vaccine candidate against human
      respiratory syncytial virus (hRSV) and human parainfluenza virus type 3 (hPIV3)
      that was previously shown to be immunogenic and to protect rodents and African
      green monkeys from wild-type (wt) hRSV challenge. We performed further
      preclinical evaluations to address the safety of MEDI-534 prior to human testing.
      MEDI-534 did not predispose rodents to enhanced RSV disease following wt-RSV
      challenge, and the tissue tropism of the chimeric virus was confined to the
      respiratory tract. Representative clinical trial material did not produce
      toxicity in rats. In adults, MEDI-534 was highly restricted in replication, did
      not boost RSV and PIV3 antibody titers, and produced no medically significant
      vaccine-related adverse events thereby warranting further evaluation in pediatric
      populations.

PMID- 18822335
TI  - Effect of H7N1 vaccination on highly pathogenic avian influenza H7N7 virus
      transmission in turkeys.
AB  - This study describes the results of a transmission experiment with highly
      pathogenic avian influenza (HPAI) H7N7 virus in 12-week-old turkeys. Cloacal and
      tracheal swabs as well as serum samples were taken to monitor the infection both
      in inoculated and in susceptible contact turkeys, which were all either
      unvaccinated, vaccinated once or vaccinated twice with H7N1. Swabs were tested by
      real-time RT-PCR and serum samples with hemagglutination inhibition test (HI).
      Unvaccinated contact birds had a mean infectious period of 6.2 days, and an
      estimated transmission rate parameter of 1.26 per infectious bird per day.
      However, no virus shedding was found in inoculated vaccinated turkeys and thus we
      concluded that vaccination with H7N1 protected against challenge with HPAI H7N7
      virus.

PMID- 18822336
TI  - Foot-and-mouth disease vaccine potency testing: the influence of serotype, type
      of adjuvant, valency, fractionation method, and virus culture on the dose
      response curve in cattle.
AB  - The aim of this study was to determine a relationship between vaccine potency
      (amount of PD50 per dose) and fraction of clinically protected cattle following
      homologous challenge with infectious foot-and-mouth disease (FMD) virus, and to
      determine the effect of method of fractionation, serotype, type of adjuvant,
      valency and type of virus culture on the dose-response curve. Data from 297
      potency tests of FMD vaccines, comprising 4004 vaccinated cattle, performed at
      the FMD vaccine production facility in the Netherlands, were used for the present
      study. A generalised linear mixed effect model was used to analyse the results.
      Our study showed that the relation between FMD vaccine potency and fraction
      protected was also affected by the serotype and type of adjuvant. No common level
      of protection could be assigned to all FMD vaccines with the same amount of PD50
      per dose, this information is essential when designing a new standard FMD
      vaccines control.

PMID- 18822337
TI  - Interactions between cytochromes P450, glutathione S-transferases and Ghanaian
      medicinal plants.
AB  - Inhibition of cytochrome P450s (CYPs) is a major cause of adverse drug-drug
      interactions. Alternatively, inhibition of glutathione S-transferases (GSTs) may
      increase harmful effects of electrophilic compounds or metabolites. In the
      present study, aqueous extracts of seven Ghanaian medicinal plants were
      investigated for their inhibitory potential towards recombinant human CYP1A2,
      CYP2C9, CYP2D6 and CYP3A4, heterologously expressed in Escherichia coli. Effects
      of these extracts on recombinant human GSTA1-1, GSTM1-1, GSTP1-1, human and rat
      cytosolic GSTs were also investigated. Seven extracts, including Phyllanthus
      amarus whole plant, leaf, stem and root, Cassia siamea and Momordica charantia,
      inhibited CYP1A2 and CYP2C9 with IC50 values ranging between 28.3-134.3microg/ml
      and between 63.4-425.9microg/ml, respectively. Similarly, both CYP2D6 and CYP3A4
      were inhibited by five extracts including Phyllanthus amarus whole plant, leaf,
      stem and root and Cassia alata, with IC50 values ranging between 45.8
      182.0microg/ml and between 79.2-158.8microg/ml respectively. Human and rat liver
      cytosolic GSTs were inhibited with IC50 values ranging between 25.2-95.5microg/ml
      and between 8.5-139.4microg/ml, respectively. GSTM1-1 was most susceptible to the
      inhibition by the extracts, with IC50 values ranging between 3.6-50.0microg/ml,
      whilst IC50 values of 8.9-159.0microg/ml and 68.6-157.0microg/ml were obtained
      for GSTA1-1 and GSTP1-1, respectively. These findings show a significant
      potential both for CYP- and GST-mediated herb-drug interactions of the Ghanaian
      medicinal plants investigated.

PMID- 18822338
TI  - Enantioselective cytotoxicity of the insecticide bifenthrin on a human amnion
      epithelial (FL) cell line.
AB  - Synthetic pyrethroids (SPs) are used in preference to organochlorines and
      organophosphates due to their high efficiency, low toxicity to mammals, and ready
      biodegradability. Previous studies reported that enantioselective toxicity of SPs
      occurs in aquatic toxicity. Several studies have indicated that SPs could lead to
      oxidative damage in humans or animals which was associated with their toxic
      effects. Little is known about the differences in the effects of chronic toxicity
      induced by individual stereoisomers of chiral SPs. The present study was
      therefore undertaken to evaluate the enantioselectivity in cytotoxicity,
      genotoxicity caused by bifenthrin (BF) on human amnion epithelial (FL) cell lines
      and pesticidal activity on target organism. The cell proliferation and cytoflow
      analysis indicated that 1S-cis-BF presented more toxic effects than 1R-cis-BF
      above the concentration of 7.5 mg L(-1) (p>0.05). FL cells incubated with 1S-cis
      BF exhibited a dose-dependent accumulation of intracellular reactive oxygen
      species (ROS). In the comet assay, the number of cells with damaged DNA incubated
      with 1S-cis-BF was more than that with 1R-cis-BF (p<0.01). While the LC(50)
      values of enantiomer to the target pest on Pieris rapae L. show that 1R-cis-BF
      was 300 times more active than 1S-cis-BF. These results indicate that the
      enantioselective toxicity and activity of BF between non-target organism and
      target organism was reversal. These implications together suggest that assessment
      of the environmental safety and new pesticides development with chiral centers
      should consider enantioselectivity.

PMID- 18822339
TI  - Inhibition of cation channels and suicidal death of human erythrocytes by
      zidovudine.
AB  - Zidovudine, a drug widely used in the treatment of AIDS, has been shown to
      influence cytosolic calcium activity in HIV-infected lymphocytes. Thus,
      zidovudine may modify the activity of Ca(2+)-permeable ion channels. In
      erythrocytes, activation of Ca(2+)-permeable cation channels stimulates
      eryptosis, the suicidal erythrocyte death. Eryptosis is characterized by cell
      shrinkage (apparent from a decrease of forward scatter) and phosphatidylserine
      (PS) exposure (apparent from annexin V-binding) at the erythrocyte surface.
      Triggers of eryptosis include isotonic cell shrinkage (Cl(-) replacement by
      gluconate), energy depletion (removal of glucose) or exposure to a variety of
      drugs including azathioprine. The present study explored, whether zidovudine
      influences the activity of erythrocytic Ca(2+)-permeable cation channels and
      eryptosis. Whole-cell patch-clamp recordings indeed revealed that zidovudine
      blocked the Ca(2+)-permeable cation channels activated by Cl(-) removal. In the
      presence of Cl(-) and glucose, the percentage of annexin V-binding cells was low
      and not significantly modified by the presence of zidovudine. Both, Cl(-) removal
      and glucose depletion increased annexin V-binding and decreased forward scatter,
      effects significantly blunted by zidovudine (2 microg/ml). According to Fluo3
      fluorescence, zidovudine (2 microg/ml) did not significantly modify cytosolic
      Ca(2+) concentration under control conditions, but significantly blunted the
      increase in cytosolic Ca(2+) activity following glucose depletion. Furthermore,
      zidovudine significantly inhibited azathioprine-induced eryptosis. The present
      observations disclose a completely novel effect of zidovudine, i.e. its
      inhibitory influence on Ca(2+) entry and subsequent suicidal erythrocyte death
      during isotonic cell shrinkage or energy depletion.

PMID- 18822340
TI  - Novel translationally controlled tumor protein homologue in the buccal gland
      secretion of Lampetra japonica.
AB  - We have cloned a homologue of the translationally controlled tumor protein (TCTP)
      from the buccal gland of Lampetra japonica according to information from a cDNA
      library and primary analysis of expressed sequence tags. Sequence analysis of L.
      japonica TCTP showed that it had two signature regions of high sequence homology
      termed TCTP-1 and TCTP-2, respectively. TCTP is highly conserved in evolution. It
      showed more than 40% identification similarities with parasite TCTPs that had
      effect on immune responses of host. Phylogeny of 31 TCTP sequences showed that
      lamprey was closer to jawed vertebrates than to Amphioxus and was a sister group
      of gnathostomes. TCTP gene from L. japonica was expressed in a pET23b vector and
      purified by using His Bind affinity chromatography. Polyclonal antibody to
      recombinant protein was generated in New Zealand Rabbit. Immunoblot analysis to
      localize the recombinant protein in buccal gland secretion proves that
      recombinant TCTP is a secretion protein, which may be secreted through a non
      classical secretion pathway. A characterization study shows that recombinant TCTP
      has histamine-releasing function in vitro. It mediated histamine release from rat
      basophilic leukemia (RBL-2H3) cells. TCTP links both the innate and the adaptive
      immune responses by modulating the secretion of cytokines from mast cells,
      basophils, eosinophils, and T and B lymphocytes. These may indicate a potential
      role of TCTP in the inflammatory process and immune regulation between L.
      japonica and host.

PMID- 18822341
TI  - The use of an unpleasant sound unconditional stimulus in an aversive conditioning
      procedure with 8- to 11-year-old children.
AB  - The study of aversive Pavlovian conditioning in children can contribute to our
      understanding of how fears are acquired and extinguished during development.
      However, methodological issues hamper further research because of ethical and
      procedural concerns regarding the use of traditional aversive unconditional
      stimuli (USs) and no established method to measure trial-by-trial changes in the
      child's expectancy of the US. The present experiment used geometric shape
      conditional stimuli (CSs) and an unpleasant sound US with 8- to 11-year-old
      children. Reliable acquisition and extinction were observed with first, second,
      and third interval skin conductance responses, on-line expectancy judgments, and
      post-conditioning subjective ratings of pleasantness and arousal. The experiment
      confirms the novel use of an unpleasant sound of metal scraping on slate as a US
      in aversive conditioning with children. The methods have the potential to
      facilitate the ethical conduct of aversive conditioning research in children
      using psychophysiological, affective, and self-report expectancy measures.

PMID- 18822342
TI  - Evolution of carrying capacity in evolution experiments focusing on a single
      locus on the Escherichia coli chromosome.
AB  - We performed a series of evolution experiments, the results of which illustrated
      the relationship between mutations and increased carrying capacity (K).
      Performing an evolution experiment with repeated cycles of mutation by PCR and
      selection makes it possible to obtain results over shorter culture durations than
      in methods reported previously relying on spontaneous mutation and selection. We
      constructed random mutant populations of Escherichia coli in which members
      differed only in part of the genomic copy of the glutamine synthetase gene and
      performed daily serial transfer culture where the populations were in K-selected
      environments. The value of K in this system was increased by 10(5)- to 10(8)-fold
      relative to the parent clone, which was achieved by four randomly introduced
      mutations. This method can be applied to any gene and will be useful for
      analyzing a number of important issues in evolutionary biology.

PMID- 18822343
TI  - The role of bone in phosphate metabolism.
AB  - Fibroblast growth factor 23 (FGF23) is a humoral factor that is produced by
      osteocytes and reduces serum phosphate and 1,25-dihydroxyvitamin D levels by
      acting on kidney through some FGF receptor and Klotho. Excessive action of FGF23
      results in several hypophosphatemic diseases characterized by impaired renal
      tubular phosphate reabsorption. In contrast, deficient action of FGF23 causes
      familial hyperphosphatemic tumoral calcinosis with enhanced renal tubular
      phosphate reabsorption. In addition, FGF23 null mice also show hyperphosphatemia.
      The production and circulatory level of FGF23 seem to be tightly regulated while
      the detailed mechanism of this regulation remains to be clarified. These results
      indicate that FGF23 is a physiological factor working as a hormone produced by
      bone. The discovery of FGF23 has revealed the possibility that bone produces
      several humoral factors to communicate with other organs.

PMID- 18822344
TI  - Pharmacophore modelling of 17beta-HSD1 enzyme based on active inhibitors and
      enzyme structure.
AB  - The 17beta-hydroxysteroid dehydrogenase type 1 (17beta-HSD1) enzyme regulates the
      conversion of estrone (E1) to the biologically active estradiol (E2). Due to its
      role as a key enzyme in female hormone production, it has emerged as an
      attractive drug target for inhibitor development in relation to hormone-dependent
      breast cancer. Herein, we report four pharmacophore models of 17beta-HSD1 based
      on a crystal structure, a relaxed crystal structure, a library of 17beta-HSD1
      inhibitors and on a docked complex of 17betaHSD1 enzyme and a potent inhibitor.
      The models were used in screening two databases, which produced novel compounds
      to be used as leads in our drug design project. The results were validated by
      docking the compounds to the active site of the 17beta-HSD1 enzyme. With the help
      of our 3D-QSAR model, these results will be used to develop new inhibitors of
      17beta-HSD1 as drug candidates.

PMID- 18822345
TI  - 11beta-Hydroxysteroid dehydrogenase type 1 inhibitors with oleanan and ursan
      scaffolds.
AB  - The enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) converts
      cortisone to the active glucocorticoid cortisol, thereby acting as a cellular
      switch to mediate glucocorticoid action in many tissues. Several studies have
      indicated that 11beta-HSD1 plays a crucial role in the onset of type 2 diabetes
      and central obesity. As a consequence, selective inhibition of 11beta-HSD1 in
      humans might become a new and promising approach for lowering blood glucose
      concentrations and for counteracting the accumulation of visceral fat and its
      related metabolic abnormalities in type 2 diabetes. In this study, we present the
      synthesis and the biological evaluation of ursan or oleanan type triterpenoids
      which may act as selective 11beta-HSD1 inhibitors in liver as well as in
      peripheral tissues, like adipocytes and muscle cells. In order to rationalise the
      outcomes of the inhibition data, docking simulations of the ligands were
      performed on the experimentally determined structure of 11beta-HSD1. Furthermore,
      we discuss the structural determinants that confer enzymatic specificity. From
      our investigation, valuable information has been obtained to design selective
      11beta-HSD1 blockers based on the oleanan and ursan scaffold.

PMID- 18822346
TI  - Evidence that TRPC1 is involved in hippocampal glutamate-induced cell death.
AB  - Massive neuronal activation by glutamate can result in an excessive rise in
      cytoplasmic calcium, a process ultimately leading to neuronal death. We have
      investigated the role of the transient receptor potential channel 1 (TRPC1) in
      mediating glutamate-induced neuron death. We show that 2-APB (a blocker of store
      operated Ca2+ entry) dramatically reduces glutamate-induced cell death in
      hippocampal organotypic slice cultures and that glutamate-induced toxicity is
      accompanied by an increase in TRPC1 expression. RNAi mediated knock-down ofTRPC1
      in slice cultures prevented glutamate-induced cell death, indicating that TRPC1
      plays a prominent role in calcium entry following exposure to glutamate. Thus,
      TRPC1 may represent a promising target for pharmacological interventions to
      prevent or reduce glutamate-induced neuronal damage.

PMID- 18822347
TI  - When they see, they see it almost right: normal subjective experience of detected
      stimuli in spatial neglect.
AB  - Unilateral spatial neglect (USN) patients show reduced contrast sensitivity on
      their contralesional side and often miss their non-salient stimuli. What their
      subjective experience is when successfully reporting a stimulus remains unclear.
      Here, we report that despite large contrast sensitivity differences between the
      sides, the relative attenuation in perceived contrast measured in a contrast
      matching task was small. This was true even at threshold levels where the
      patients missed up to 40% of the contralesional target patches, in contrast to a
      100% detection rate on their ipsilesional side. When the misses were counted as
      zero perceived contrast events, the attenuation in perceived contrast was less
      than half of the sensitivity loss. When the misses were ignored, there was almost
      no attenuation in perceived contrast, implying that whenever the patients
      detected a target, they perceived it with the correct contrast. These findings
      suggest that contrast sensitivity reduction in USN is not due to attenuation
      occurring at a peripheral low-level processing stage. More likely it reflects a
      high-threshold added at a higher level of processing, which prevents sensory
      events from reaching conscious awareness. Hence, patients may often miss
      contralesional stimuli but see them in full contrast once they clear the high
      level hurdle.

PMID- 18822348
TI  - Integration of cortical areas during performance of a catching ball task.
AB  - The study aimed to elucidate electrophysiological and cortical mechanisms
      involved in anticipatory actions when healthy subjects had to catch balls in free
      drop; specifically through quantitative electroencephalography (qEEG) alpha
      absolute power changes. Our hypothesis is that during the preparation of motor
      action (i.e., 2s before ball's drop) occurred integration among left medial
      frontal, left primary somatomotor and left posterior parietal cortices, showing a
      differentiated activity involving expectation, planning and preparedness. This
      hypothesis supports a lateralization of motor function. Although we contend that
      in right-handers the left hemisphere takes on a dominant role for the regulation
      of motor behavior. The sample was composed of 23 healthy subjects (13 male and 10
      female), right handed, with ages varying between 25 and 40 years old (32.5+/
      7.5), absence of mental and physical illness, right handed, and do not make use
      of any psychoactive or psychotropic substance at the time of the study. The
      experiment consisted of a task of catching balls in free drop. The three-way
      ANOVA analysis demonstrated an interaction between moment and position in left
      medial frontal cortex (F3 electrode), somatomotor cortex (C3 electrode) and
      posterior parietal cortex (P3 electrode; p < 0.001). Summarizing, through
      experimental task employed, it was possible to observe integration among frontal,
      central and parietal regions. This integration appears to be more predominant in
      expectation, planning and motor preparation. In this way, it established an
      absolute predominance of this mechanism under the left hemisphere.

PMID- 18822349
TI  - Quantitative analysis of activated caspase-3-positive cells and a circadian cycle
      of programmed cell death in the adult teleost retina.
AB  - In adult teleosts, it has been shown that germinal cells proliferate in the
      marginal retina. Daughter cells also die in this region but the details of their
      death, presumably by programmed cell death (PCD), are not fully known. In this
      study, we labeled cells undergoing PCD in the adult goldfish retina by an
      antibody to activated caspase-3. Most of the activated caspase-3-positive cells
      (caspase-3+ cells) were found at the primary growth zone in the retinal margin,
      80-140 microm from the circular blood vessel, where their density was 518+/-65.3
      cells/mm2 of the retinal surface (mean+/-S.D., n = 3) at midday and 395+/-47.4
      cells/mm2 (n = 3) at midnight. Although the local densities of caspase-3+ cells
      in the primary growth zone in the day and night-time were significantly
      different, the mean densities of caspase-3+ cells in the retinal margin as a
      whole remained constant at 185+/-29.7 cells/mm2 (n = 16) during most of the day
      and night-time. However, immediately after light onset in the morning, the
      density of caspase-3+ cells in the retinal margin increased by 30%. This
      transient increase was also seen at the same objective time in goldfish that were
      kept in the dark for the entire day. Our quantitative study demonstrates that PCD
      in the marginal retina of the adult goldfish is induced in some parts by a
      caspase-3-dependent pathway and that it is also regulated by a circadian
      mechanism.

PMID- 18822350
TI  - Intranasally delivered bFGF enhances neurogenesis in adult rats following
      cerebral ischemia.
AB  - Basic fibroblast growth factor (bFGF) is a very important mitogenic factor with
      proved neurogenesis effects in the central nervous system. Intranasal
      administration can bypass blood-brain barrier and deliver drugs into the brain
      directly. We investigated whether intranasal administration of bFGF at later time
      points after ischemia could promote adult neurogenesis and improve neurologic
      functions. Rats received bFGF or saline intranasally once daily for 6 consecutive
      days, starting at 1 day after transient middle cerebral artery occlusion (MCAO).
      Bromodeoxyuridine (BrdU) was injected at 5 and 6 days after MCAO. Rats were
      killed at 7 or 28 days after MCAO. Neurogenesis was assessed by immunostaining
      for BrdU and cell type-specific markers. Neurological functions were evaluated by
      the modified Neurological Severity Scores. Compared with the control animals,
      intranasal administration of bFGF improved behavioral recovery without affecting
      infarct size, and enhanced proliferation of progenitor cells in the
      subventricular zone and the subgranular zone of the dentate gyrus (DG).
      Furthermore, the new proliferated cells could differentiate into neurons
      (BrdU+NeuN+ cells) in the striatum and DG at 28 days after MCAO. Intranasal
      administration of bFGF offers a non-invasive alternative for the treatment of
      stroke.

PMID- 18822351
TI  - Identification of aquaporin-5 and lipid rafts in human resting saliva and their
      release into cevimeline-stimulated saliva.
AB  - BACKGROUND: It is unknown whether AQP5 and lipid rafts are released into human
      unstimulated (resting) saliva and saliva in response to secretagogues. METHODS:
      In order to quantitate the salivary concentration of AQP5, we produced a
      polyclonal antibody for human AQP5 and developed an enzyme-like immunosorbent
      assay (ELISA). RESULTS: AQP5 and lipid rafts were identified in human resting
      saliva. The amount of AQP5 in resting saliva showed a diurnal variation with high
      levels during waking hours, and an age-related decrease in AQP5 was coincident
      with the volume of resting saliva. Cevimeline, a muscarinic acetylcholine
      receptor (mAChR) agonist, induced the release of AQP5 with lipid rafts, amylase,
      mucin, and lysozyme. Changes in saliva AQP5 levels after cevimeline
      administration occurred simultaneously with changes in saliva flow rates.
      Confocal microscopy revealed that AQP5 was located in the apical plasma membrane
      and showed a diffuse pattern in parotid glands under resting conditions.
      Following cevimeline administration, AQP5 was predominantly associated with the
      APM and was localized in the lumen. GENERAL SIGNIFICANCE: AQP5 and lipid rafts
      were released with salivary proteins from human salivary glands by the
      stimulation of M3 mAChRs, and that changes in saliva AQP5 levels can be used as
      an indicator of salivary flow rate and also as a useful index of M3 mAChR
      agonist's action on human salivary glands.

PMID- 18822352
TI  - Elevated pressure triggers a physiological release of ATP from the retina:
      Possible role for pannexin hemichannels.
AB  - Increased hydrostatic pressure can damage neurons, although the mechanisms
      linking pressure to neurochemical imbalance or cell injury are not fully
      established. Throughout the body, mechanical perturbations such as shear stress,
      cell stretching, or changes in pressure can lead to excessive release of ATP. It
      is thus possible that increased pressure across neural tissues triggers an
      elevated release of ATP into extracellular space. As stimulation of the P2X(7)
      receptor for ATP on retinal ganglion cells leads to elevation of intracellular
      calcium and excitotoxic death, we asked whether increased levels of extracellular
      ATP accompanied an elevation in pressure across the retina. The hydrostatic
      pressure surrounding bovine retinal eyecups was increased and the ATP content of
      the vitreal compartment adjacent to the retina was determined. A step increase of
      only 20 mm Hg induced a threefold increase in the vitreal ATP concentration. The
      ATP levels correlated closely with the degree of pressure increase over 20-100 mm
      Hg. The increase was transient at lower pressures but sustained at higher
      pressures. The rise in vitreal ATP was the same regardless of whether nitrogen or
      air was used to increase pressure, implying changes in oxygen partial pressure
      did not contribute. Lactate dehydrogenase activity was not affected by pressure,
      ruling out a substantial contribution from cell lysis. The ATP increase was
      largely inhibited by either 30 muM 5-nitro-2-(3-phenylpropylamino) benzoic acid
      (NPPB) or 10 muM carbenoxolone (CBX). While this pharmacological profile is
      consistent with physiological release of ATP through pannexins hemichannels, a
      contribution from anion channels, vesicular release or other mechanisms cannot be
      ruled out. In conclusion, a step elevation in pressure leads to a physiologic
      increase in the levels of extracellular ATP bathing retinal neurons. This excess
      extracellular ATP may link increased pressure to the death of ganglion cells in
      acute glaucoma, and suggests a possible role for ATP in the neuronal damage
      accompanying increased intracranial pressure.

PMID- 18822353
TI  - The anandamide membrane transporter inhibitor, VDM-11, modulates sleep and c-Fos
      expression in the rat brain.
AB  - Endogenous cannabinoids or endocannabinoids are lipid molecules that have a
      variety of biological actions, most notably via activation of the cannabinoid
      receptors. The family of endocannabinoids includes arachidonoylethanolamide (ANA)
      which modulates different behaviors, such as sleep. However, it is unknown
      whether pharmacological elevation of ANA endogenous levels might induce sleep.
      VDM 11 [(5 Z,8 Z,11 Z,14 Z)-N-(4-hydroxy-2-methylphenyl)-5,8,11,14
      eicosatetraenamide] is commonly used as an inhibitor of ANA cellular uptake, and
      thereby to potentiate its actions. In this study we have examined whether VDM-11
      exerts any effect on the sleep-wake cycle and c-Fos expression in brain areas.
      When assayed alone in rats, VDM-11 (10 or 20 microg/5 microL, i.c.v.) at the
      beginning of the lights-off period, reduced wakefulness and increased sleep. The
      CB(1) cannabinoid receptor antagonist, SR141716A, partially reversed the effects
      of VDM-11 on sleep. Additionally, VDM-11 enhanced c-Fos expression in sleep
      related brain areas such as the anterior hypothalamic area, paraventricular
      thalamic nucleus, and pedunculopontine tegmental nucleus. It is concluded that
      VDM-11 displays sleep-inducing properties and these effects slightly, albeit
      significantly, are reversed using SR141716A. Furthermore, c-Fos data suggest a
      possible underlying neuroanatomical substrate of the sleep-inducing properties of
      VDM-11. We report evidence suggesting that VDM-11 might be considered for the
      development of new pharmacological and pharmaceutical approaches to treat sleep
      disorders such as insomnia.

PMID- 18822354
TI  - Alpha(2)-noradrenergic antagonist administration into the central nucleus of the
      amygdala blocks stress-induced hypoalgesia in awake behaving rats.
AB  - Stress-induced hypoalgesia (SIH) is an adaptive behavioral phenomenon mediated in
      part by the amygdala. Acute stress increases amygdalar noradrenaline levels and
      focal application of alpha(2)-adrenoceptor agonists in the central nucleus of the
      amygdala (CeA) is antinociceptive. We hypothesized that alpha(2)-adrenoceptor
      antagonist administration into the CeA may block SIH. Bilateral microinjections
      of drug or saline via chronically implanted CeA cannulae were followed by either
      a period of restraint stress or rest. The nocifensive paw-withdrawal latency
      (PWL) to a focused beam of light was measured. PWLs were longer in restrained
      rats, constituting SIH. Microinjection of the alpha(2)-adrenoceptor antagonist
      idazoxan into the CeA prior to restraint blocked SIH. Idazoxan administration in
      unrestrained rats had no effect. Microinjection of the alpha(2)-adrenoceptor
      agonist clonidine in unrestrained rats caused dose dependent hypoalgesia,
      mimicking the effects of environmental stress. alpha(2)-Adrenoceptor function in
      the CeA is necessary for restraint-induced SIH.

PMID- 18822355
TI  - Stress- and non-stress-mediated mechanisms are involved in pain-induced apoptosis
      in hippocampus and dorsal lumbar spinal cord in rats.
AB  - Chronic pain has been reported to induce apoptosis. Both chronic excitation of
      neural pathways involved in pain transmission and control and the stress of pain
      may be potentially involved in apoptosis induced by pain. Here, we have
      investigated their possible role in pain-induced apoptosis. Inflammatory pain was
      induced by injection of formalin in intact and adrenalectomized (ADX) rats.
      Following exposure to repeated injections of 5% formalin, we detected Bax, Bcl-2,
      pro-caspase and activated caspase-3 proteins using immunoblotting. The results
      were compared with those obtained from animals suffered from chronic
      immobilization stress (IMO). These results showed an increased ratio of Bax/Bcl-2
      and activated caspase-3 in hippocampus and dorsal lumbar spinal cord of animals
      treated with pain and IMO stress; these effects were reduced in ADX animals. On
      the other hand, the remaining apoptotic effect of pain in adrenalectomized rats
      was also significant. We surmise that both chronic neural activation and the
      stress induced by pain are involved in pain-induced apoptosis.

PMID- 18822356
TI  - Attempt to record electrical cerebral activity.

PMID- 18822357
TI  - Evaluation of behavioural effects of a selective NMDA NR1A/2B receptor antagonist
      in the unilateral 6-OHDA lesion rat model.
AB  - The degeneration of the dopaminergic nigrostriatal pathway in Parkinson's disease
      (PD) is associated with altered transmission at striatal NMDA receptors
      containing NR2B subunits. We investigated a potential novel therapeutic compound,
      4-trifluoromethoxy-N-(2-trifluoromethyl-benzyl)-benzamidine (BZAD-01), a
      selective NMDA NR1A/2B receptor antagonist for PD and compared it with levodopa,
      the standard treatment for PD. This study also evaluated whether combining
      levodopa and BZAD-01 gave better improvements of parkinsonian symptoms.
      Parkinsonism was induced by microinjection of the toxin, 6-hydroxydopamine (6
      OHDA) into the medial forebrain bundle (MFB) of 40 Sprague-Dawley rats.
      Parkinsonism and the efficacy of drugs were assessed using a battery of
      behavioural tests including balance beam, apomorphine-induced rotation, body axis
      bias or "curling", head position bias and disengage sensorimotor latency test.
      Immunohistochemistry was performed on post-mortem tissue to estimate the loss of
      dopaminergic neurons. The main effects were that BZAD-01 co-administration
      prevented chronic levodopa-induced potentiation of apomorphine rotation. However
      levodopa-treated rats were slower than either controls or BZAD-01-treated rats in
      the locomotor test. The improvement in the apomorphine rotation test suggests
      that BZAD-01 may be a useful adjunct to levodopa monotherapy.

PMID- 18822358
TI  - Comparison of the diagnostic performance of human whole genome microarrays using
      mixed-tissue RNA reference samples.
AB  - Universal approaches for assessing the diagnostic performance of microarray
      assays are essential for the application of microarray technology to clinical and
      regulatory settings. Reference systems for diagnostic assays in laboratory
      medicine typically involve the utilization of reference samples, metrics, and
      reference datasets to ensure that measurements are comparable and true. For
      microarray performance evaluation and process improvement, reference samples can
      be composed of mixes of different tissue or cell line RNAs that contain tissue
      selective analytes at defined target ratios. The diagnostic accuracy of detected
      changes in expression, measured as the area under the curve from receiver
      operating characteristic plots, can provide a single commutable value for
      comparing assay specificity and sensitivity. Examples of applying this method for
      assessing overall performance are provided using public datasets generated on
      five commercial human whole genome microarray platforms for the MicroArray
      Quality Control project, a community-wide effort to address issues surrounding
      microarray data reliability.

PMID- 18822359
TI  - Application of toxicogenomics to study mechanisms of genotoxicity and
      carcinogenicity.
AB  - Specific genotoxic events such as gene mutations and/or chromosome damage are
      considered hallmarks of cancer. The genotoxicity testing battery enables
      relatively simple, rapid and inexpensive hazard identification, namely by
      assessing a chemical's ability to cause genetic damage in cells. In addition, the
      2-year rodent carcinogenicity bioassay provides an assessment of a risk
      associated with the chemical to develop cancer in animals. Although the link
      between genotoxicity and carcinogenicity is well documented, this relationship is
      complicated due to the impact of non-genotoxic mechanisms of carcinogenesis and
      by character of the in vitro genotoxicity assays and specific endpoints making
      the interpretation of test results in light of human risk and relevance
      difficult. In particular, the specificity of test results has been questioned.
      Therefore, the development of novel scientific approaches bridging genotoxicity
      and carcinogenicity testing via understanding underlying mechanisms is extremely
      important for facilitating cancer risk assessment. In this respect,
      toxicogenomics approaches are considered promising as these have the potential of
      providing generic insight in molecular pathway responses. The goal of this report
      thus is to review recent progress in the development and application of
      toxicogenomics to the derivation of genomic biomarkers associated with mechanisms
      of genotoxicity and carcinogenesis. Furthermore, the potential for application of
      genomic approaches to hazard identification and risk assessment is explored.

PMID- 18822360
TI  - Dithiocarbamate propineb induces acetylcholine release through cytoskeletal actin
      depolymerization in PC12 cells.
AB  - Neurological complications as well as movement disorders are relevant symptoms in
      animals and humans chronically exposed to dithiocarbamates. Using rat
      pheochromocytoma cells differentiated by NGF (PC12), we investigated whether
      propineb affects acetylcholine (Ach) release and the molecular mechanisms
      involved. Propineb (0.001-100 nM) dose-dependently increased Ach release from
      PC12. Thus, 0.001-1 nM propineb-induced Ach release, reaching a maximal effect (
      approximately 50%) at 0.1-1 nM. Higher concentrations of propineb (10-100 nM)
      caused a progressive disappearance of the effect. Chelation of extra- and
      intracellular Ca(2+) did not affect Ach release by propineb, which was prevented
      by the actin stabilizer jasplakinolide (500 nM). Accordingly, actin
      depolymerization was observed after exposure of differentiated PC12 to 0.1-1 nM
      propineb, a loss of effect was evident at higher concentrations (100 nM), and the
      effect was Ca(2+)-independent. Disulfiram, a related dithiocarbamate not
      coordinated with Zn(2+), also depolymerized actin, suggesting the involvement of
      the organic structure of dithiocarbamates rather than the leakage of Zn(2+).
      Nevertheless, propineb did not depolymerize actin in a cell-free system. These
      data suggest that dithiocarbamates, through the activation of intracellular
      cascade(s), impair cytoskeletal actin. This effect may contribute to affect
      synaptic vesicles processing resulting in an impaired cholinergic transmission.

PMID- 18822361
TI  - In situ gel based on gellan gum as new carrier for nasal administration of
      mometasone furoate.
AB  - The main purpose of this study was to prepare a novel in situ gel system for
      nasal delivery of MF and study its efficacy on allergic rhinitis model. An ion
      activated in situ gel was developed and characterized with gellan gum as a
      carrier. The system was stable kept at 40+/-2 degrees C for 6 months, and the
      micrographic results showed that in situ gel was safety without mucosa irritation
      when given at 20 microg once daily for 1 month to rats with allergic rhinitis. MF
      in gellan gum produced obviously effect on allergic rhinitis at the doses of 20
      microg/body following intranasal administration, and the efficacy was
      significantly superior to that of the common suspension (P<0.01). The in situ gel
      system is a promising approach for the intranasal delivery of MF for the
      therapeutic effects improvement.

PMID- 18822362
TI  - Mathematical modeling of drug delivery.
AB  - Due to the significant advances in information technology mathematical modeling
      of drug delivery is a field of steadily increasing academic and industrial
      importance with an enormous future potential. The in silico optimization of novel
      drug delivery systems can be expected to significantly increase in accuracy and
      easiness of application. Analogous to other scientific disciplines, computer
      simulations are likely to become an integral part of future research and
      development in pharmaceutical technology. Mathematical programs can be expected
      to be routinely used to help optimizing the design of novel dosage forms. Good
      estimates for the required composition, geometry, dimensions and preparation
      procedure of various types of delivery systems will be available, taking into
      account the desired administration route, drug dose and release profile. Thus,
      the number of required experimental studies during product development can be
      significantly reduced, saving time and reducing costs. In addition, the
      quantitative analysis of the physical, chemical and potentially biological
      phenomena, which are involved in the control of drug release, offers another
      fundamental advantage: The underlying drug release mechanisms can be elucidated,
      which is not only of academic interest, but a pre-requisite for an efficient
      improvement of the safety of the pharmaco-treatments and for effective trouble
      shooting during production. This article gives an overview on the current state
      of the art of mathematical modeling of drug delivery, including empirical/semi
      empirical and mechanistic realistic models. Analytical as well as numerical
      solutions are described and various practical examples are given. One of the
      major challenges to be addressed in the future is the combination of mechanistic
      theories describing drug release out of the delivery systems with mathematical
      models quantifying the subsequent drug transport within the human body in a
      realistic way. Ideally, the effects of the design parameters of the dosage form
      on the resulting drug concentration time profiles at the site of action and the
      pharmacodynamic effects will become predictable.

PMID- 18822363
TI  - Physical chemistry behavior of enteric polymer in drug release systems.
AB  - We report an analysis based on the electrical impedance (EI) spectrum of the
      samples of enteric random copolymer poly-methacrylic acid-co-methyl methacrylate
      as a function of pH of media. Important aspects of the charge transport and
      conformational processes in enteric polymer can be identified by mapping the
      complex impedance as a function of the frequency, which allows that some
      parallelism between titration and EI measurements can be obtained. However, the
      latter technique reveals details of this complex equilibrium that not appear
      using common titration methods. The relaxation frequency observed in the
      impedance spectrum act as a probe for the detection of phase transitions and
      conformational changes of the polymeric chains, once the distribution of size of
      particles can be related with this parameter. The progressive introduction of the
      alkali and the variation of pH between 4 and 10 are associated with a three steps
      process, related to the equilibrium shift from a precipitated solid or
      suspension, to a colloidal-like dispersion and to a complete solubilization of
      the copolymer. All those experimental features were reflected simultaneously as a
      turning point in plots of impedance, relaxation frequency and visible absorption
      with alkali addition giving a better and detailed insight to these processes.

PMID- 18822364
TI  - Azithromycin loaded on hydrogels of carbomer: chemical stability and delivery
      properties.
AB  - Hydrogels of carbomer (C) and azithromycin (AZI) were prepared by neutralizing
      with AZI 50% of the carboxylic groups of 0.25% C(974) and C(934) dispersions. The
      hydrogels exhibit pH close to 8 and are physically stable. Titration with NaCl
      revealed a high degree of counterion condensation C-AZI. The release of AZI in a
      Franz cell was almost negligible when the receptor compartment was filled with
      water but was increased about 20 times as water is replaced by NaCl solution. Two
      analytical methods were used to evaluate the effect of the counterionic
      condensation on the chemical stability of AZI, a microbial assay and an HPLC
      method. Degradation of AZI in buffered aqueous solution was used as reference.
      The stability of AZI was significantly improved in the hydrogels retaining more
      than 75% of the initial concentration along a period of 18-20 months evaluated
      and the self life (t(90)) of the drug was increased 27 and 20 times over the
      reference. The improvement of AZI stability could be attributed to the high
      degree of counterion condensation in which drug molecules remain associated to
      the macromolecular phase having a high negative electrokinetic potential and
      higher viscosity and lower kinetic energy than those in the fluid phase.

PMID- 18822365
TI  - Anticonvulsant activity of Carissa edulis (Vahl) (Apocynaceae) root bark extract.
AB  - AIM OF THE STUDY: To investigate the anticonvulsant activity of root bark extract
      of Carissa edulis. MATERIALS AND METHODS: The median lethal dose (LD(50)) of
      Carissa edulis extract was determined using Lork's method (1983). The
      anticonvulsant activity of the extract was assessed in pentylenetetrazole (PTZ)
      induced convulsion in mice and maximal electroshock test (MEST) in chicks, with
      benzodiazepine and phenytoin as standard drugs, respectively. While mechanistic
      studies were conducted using both flumazenil, a GABA(A)-benzodiazepine receptor
      complex site antagonist and naloxone a non-specific opioid receptor antagonist.
      RESULTS: The median lethal dose (LD(50)) of Carissa edulis was 282.8mg/kg and
      over 5000mg/kg following intraperitoneal and oral administration, respectively.
      Carissa edulis produced 40% and 20% protection against convulsion at 5 and
      20mg/kg, respectively, compared with 100% protection with benzodiazepine. The
      mean onset and percentage protection against convulsion in Carissa edulis extract
      treated mice were reduced by flumazenil and naloxone. Carissa edulis exhibited
      dose-dependent inhibition of the convulsion induced by MEST with 20mg/kg
      providing 90% protection while phenytoin (20mg/kg) produced 100% protection.
      CONCLUSION: These results suggest that Carissa edulis possesses biologically
      active constituent(s) that have anticonvulsant activity which supports the
      ethnomedicinal claims of the use of the plant in the management of epilepsy.

PMID- 18822366
TI  - Genetic association analysis of copy-number variation (CNV) in human disease
      pathogenesis.
AB  - Structural genetic variation, including copy-number variation (CNV), constitutes
      a substantial fraction of total genetic variability and the importance of
      structural genetic variants in modulating human disease is increasingly being
      recognized. Early successes in identifying disease-associated CNVs via a
      candidate gene approach mandate that future disease association studies need to
      include structural genetic variation. Such analyses should not rely on previously
      developed methodologies that were designed to evaluate single nucleotide
      polymorphisms (SNPs). Instead, development of novel technical, statistical, and
      epidemiologic methods will be necessary to optimally capture this newly
      appreciated form of genetic variation in a meaningful manner.

PMID- 18822367
TI  - Cautionary insights on knockout mouse studies: the gene or not the gene?
AB  - Gene modification technologies play a vital role in the study of biological
      systems and pathways. Although there is widespread and beneficial use of genetic
      mouse models, potential shortcomings of gene targeting technology exist, and are
      not always taken into consideration. Oversights associated with the technology
      can lead to misinterpretation of results; for example, ablation of a gene of
      interest can appear to cause an observed phenotype when, in fact, residual
      embryonic stem cell-derived genetic material in the genetic background or in the
      area immediately surrounding the ablated gene is actually responsible. The
      purpose of this review is to remind researchers, regardless of scientific
      discipline, that the background genetics of a knockout strain can have a profound
      influence on any observed phenotype. It is important that this issue be
      appropriately addressed during data collection and interpretation.

PMID- 18822368
TI  - Protective effect of Pycnogenol in human neuroblastoma SH-SY5Y cells following
      acrolein-induced cytotoxicity.
AB  - Oxidative stress is one of the hypotheses involved in the etiology of Alzheimer's
      disease (AD). Considerable attention has been focused on increasing the
      intracellular glutathione (GSH) levels in many neurodegenerative diseases,
      including AD. Pycnogenol (PYC) has antioxidant properties and stabilizes
      intracellular antioxidant defense systems including glutathione levels. The
      present study investigated the protective effects of PYC on acrolein-induced
      oxidative cell toxicity in cultured SH-SY5Y neuroblastoma cells. Decreased cell
      survival in SH-SY5Y cultures treated with acrolein correlated with oxidative
      stress, increased NADPH oxidase activity, free radical production, protein
      oxidation/nitration (protein carbonyl, 3-nitrotyrosine), and lipid peroxidation
      (4-hydroxy-2-nonenal). Pretreatment with PYC significantly attenuated acrolein
      induced cytotoxicity, protein damage, lipid peroxidation, and cell death. A dose
      response study suggested that PYC showed protective effects against acrolein
      toxicity by modulating oxidative stress and increasing GSH. These findings
      provide support that PYC may provide a promising approach for the treatment of
      oxidative stress-related neurodegenerative diseases such as AD.

PMID- 18822369
TI  - Leishmania major ascorbate peroxidase overexpression protects cells against
      reactive oxygen species-mediated cardiolipin oxidation.
AB  - Heme peroxidases are a class of multifunctional redox-active proteins found in
      all organisms. We recently cloned, expressed, and characterized an ascorbate
      peroxidase from Leishmania major (LmAPX) that was capable of detoxifying hydrogen
      peroxide. Localization studies using green fluorescent protein fusions revealed
      that LmAPX was localized within the mitochondria by its N-terminal signal
      sequence. Subcellular fractionation analysis of the cell homogenate by the
      Percoll density-gradient method and subsequent Western blot analysis with anti
      LmAPX antibody further confirmed the mitochondrial localization of mature LmAPX.
      Submitochondrial fractionation analysis showed that the mature enzyme (~3.6 kDa
      shorter than the theoretical value of the whole gene) was present in the
      intermembrane space side of the inner membrane. Moreover, expression of the LmAPX
      gene was increased by treatment with exogenous H(2)O(2), indicating that LmAPX
      was induced by oxidative stress. To investigate the biological role of LmAPX we
      generated Leishmania cells overexpressing LmAPX in the mitochondria. Flow
      cytometric analysis, thin-layer chromatography, and IC(50) measurements suggested
      that overexpression of LmAPX caused depletion of the mitochondrial ROS burden and
      conferred a protection against mitochondrial cardiolipin oxidation and increased
      tolerance to H(2)O(2). These results suggest that the single-copy LmAPX gene
      plays a protective role against oxidative damage.

PMID- 18822370
TI  - Increased oxidative stress and astrogliosis responses in conditional double
      knockout mice of Alzheimer-like presenilin-1 and presenilin-2.
AB  - Conditional presenilin 1 and presenilin 2 double knockout causes memory
      dysfunction and reproduces neurodegenerative phenotypes of Alzheimer disease (AD)
      in mice. Oxidative stress has been long implicated predominantly in amyloidosis
      mediated AD pathologies; however, its role in response to the loss-of-function
      pathogenic mechanism of AD remains unclear. In this study, we examined the
      oxidative stress status in PS1 and PS2 double-knockout (PS cDKO) mice using F(2)
      isoprostanes (iPF(2alpha)-III) as the marker of lipid peroxidation. Lipid
      peroxidation was enhanced in a gender- and age-related manner in the PS cDKO mice
      independent of brain Abeta deposition. Such oxidative abnormalities predominantly
      in cerebral cortex at 2-4 months of age preceded the onset of many pronounced AD
      neuropathologies, suggesting that increased lipid peroxidation is not only an
      early pathophysiological response to PS inactivation, but also a potential
      culprit responsible for the AD-like neurodegenerative pathologies in the PS cDKO
      mice. Western blot analysis of cortical glial fibrillary acidic protein
      demonstrated an increased astrogliosis response to PS inactivation, in particular
      in the PS cDKO mice at as young as 2 months of age, suggesting that lipid
      peroxidation and neuronal injury may be closely associated with the loss-of
      function neuropathogenic mechanism of AD.

PMID- 18822371
TI  - Effects of prenatal cocaine exposure on infant reactivity and regulation.
AB  - The purpose of this study was to examine the role of prenatal cocaine exposure
      and associated risk factors on infant reactivity and regulation at 7 months of
      infant age. Participants consisted of 167 mother-infant dyads participating in an
      ongoing longitudinal study of prenatal cocaine exposure, who completed the arm
      restraint procedure at the 7-month assessment (87 cocaine exposed, 80 non-cocaine
      exposed). We hypothesized that cocaine exposed infants would display higher
      arousal or reactivity and lower regulation during a procedure designed to arouse
      anger/frustration. Results indicated that cocaine exposed infants were more
      reactive to increases in the level of stress from trial 1 to trial 2 but
      exhibited no change in the number of regulatory strategies as stress increased,
      unlike the control group infants. Infant birth weight moderated the association
      between cocaine exposure and infant regulation. Among cocaine exposed infants,
      those with lower birth weight displayed higher reactivity compared to those with
      higher birth weight. Contrary to expectations, there were no indirect effects
      between cocaine exposure and infant reactivity/regulation via environmental risk,
      parenting, or birth weight. Results are supportive of a teratological model of
      prenatal cocaine exposure for infant reactivity/regulation in infancy.

PMID- 18822372
TI  - Controlling cell surface dynamics and signaling: how CD82/KAI1 suppresses
      metastasis.
AB  - The recent identification of metastasis suppressor genes, uniquely responsible
      for negatively controlling cancer metastasis, are providing inroads into the
      molecular machinery involved in metastasis. While the normal function of a few of
      these genes is known; the molecular events associated with their loss that
      promotes tumor metastasis is largely not understood. KAI1/CD82, whose loss is
      associated with a wide variety of metastatic cancers, belongs to the tetraspanin
      family. Despite intense scrutiny, many aspects of how CD82 specifically functions
      as a metastasis suppressor and its role in normal biology remain to be
      determined. This review will focus on the molecular events associated with CD82
      loss, the potential impact on signaling pathways that regulate cellular processes
      associated with metastasis, and its relationship with other metastasis suppressor
      genes.

PMID- 18822373
TI  - IgE receptor and signal transduction in mast cells and basophils.
AB  - There are many aspects of mast cell and basophil biology that are being explored
      today. Notably, there is a wide variety of studies of the roles these two cell
      types play in the development of a multitude of diseases and the role they play
      in the general immune response. But the original reasons for studying these two
      cells types--because they are considered crucial to immediate hypersensitivity
      reactions--remain a driving force for research. These two cell types express the
      complete high affinity IgE receptor and aggregation of this receptor results in
      the secretion of multiple potent mediators that cause many of the signs and
      symptoms of an allergic reaction. Understanding more about the biology of the
      receptor and the signaling that it initiates remains important to the development
      of new therapeutic approaches to inhibit this reaction.

PMID- 18822374
TI  - A transcribed polyketide synthase gene from Xanthoria elegans.
AB  - We characterize the transcript of a polyketide synthase gene (PKS) from the
      cultured mycobiont of Xanthoria elegans (XePKS1) using SMART-rapid amplification
      of cDNA ends (RACE) cDNA synthesis. Sequence analysis of the cloned cDNA reveals
      an open reading frame of 2144 amino acid residues. It contains features of a non
      reducing fungal type I PKS with an N-terminal starter unit: acyl carrier protein
      (ACP) transacetylase domain, ketosynthase, acyltransferase, two acyl carrier
      protein domains, and a thioesterase domain. XePKS1 was the only paralogue
      detected in the cDNA and the genomic DNA of the cultured X. elegans mycobiont by
      using a degenerate PCR approach targeted at the conserved regions of non-reducing
      type I PKS genes. The hypothetical protein is phylogenetically related to genes
      that are basal to a clade of dihydroxynaphthalene synthases (non-reducing clade
      II) and anthraquinone type synthases of non-lichenized fungi (non-reducing clade
      I). According to hplc and tlc analyses, the cultured mycobiont exclusively
      produced anthraquinones and its precursors. Therefore, we discuss whether the
      characterized paralogue is involved in anthraquinone production, which raises the
      possibility of a paraphyletic origin of lichen anthraquinone biosynthesis. The
      cDNA of XePKS1 was the first full-length coding sequence of a lichen PKS to be
      published. This proves SMART RACE to be a suitable tool for obtaining full-length
      coding sequences of genes from environmental samples and organisms, which are
      hardly amenable to standard molecular approaches or genomic sequencing.

PMID- 18822375
TI  - Glycosyltransferases, glycoside hydrolases: surprise, surprise!
AB  - Several in the field-and many outside-consider that solving the three-dimensional
      structures of more glycoside hydrolases (GHs) and glycosyltransferases (GTs)
      confines to stamp collection and some even think that there is no main revelation
      to expect in this area. It is wrong! The past year has come as a refreshing wake
      up call with major surprises for both GHs and GTs.

PMID- 18822376
TI  - Molecular mechanisms of O-GlcNAcylation.
AB  - Protein glycosylation with O-linked N-acetylglucosamine (O-GlcNAc) is a
      reversible post-translational modification of serines/threonines on metazoan
      proteins and occurring with similar time scales, dynamics and stoichiometry as
      protein phosphorylation. Levels of this modification are regulated by two enzymes
      O-GlcNAc transferase (OGT) and O-GlcNAc hydrolase (OGA). Although the
      biochemistry of these enzymes and functional implications of O-GlcNAc have been
      studied extensively, until recently the structures and molecular mechanisms of
      OGT/OGA were not understood. This review covers a body of recent work that has
      led to an understanding of the structure of OGA, its catalytic mechanism and the
      development of a plethora of different inhibitors that are finding their use in
      cell biological studies towards the functional implications of O-GlcNAc.
      Furthermore, the very recent structure determination of a bacterial OGT
      orthologue has given the first insights into the contribution of the
      tetratricopeptide repeats (TPRs) to the active site and the role of some residues
      in catalysis and substrate binding.

PMID- 18822377
TI  - Putting glycobiology on a structural footing.

PMID- 18822378
TI  - Aromatase is phosphorylated in situ at serine-118.
AB  - Phosphorylation of the cytochrome P450 aromatase has been proposed as a switch to
      rapidly modulate enzymatic activity and estrogen biosynthesis. Herein, we
      demonstrate that aromatase serine-118 is a potential phosphorylation site in
      mammalian cells. The amino acid context surrounding S118 is highly conserved
      among diverse animal species and suggests that an AGC-like kinase may
      phosphorylate aromatase. Mutation of S118 to Ala blocked phosphorylation.
      Mutation of S118 to either Ala or Asp destabilized aromatase, indicating an
      important structural role for S118. The phosphomimetic S118D mutant showed
      decreased specific enzymatic activity, decreased Vmax, and increased Km, while
      the S118A phospho-inhibiting mutant showed opposite effects. Our findings suggest
      that phosphorylation of S118 may decrease aromatase activity, presenting a
      mechanism whereby kinase signaling may modulate estrogen production and hormone
      balance.

PMID- 18822379
TI  - Anabolic activity of ursolic acid in bone: Stimulating osteoblast differentiation
      in vitro and inducing new bone formation in vivo.
AB  - In the field of osteoporosis, there has been growing interest in anabolic agents
      that enhance bone mass and improve bone architecture. In this study, we
      demonstrated that the ubiquitous plant triterpenoid, ursolic acid, enhances
      differentiation and mineralization of osteoblasts in vitro. We found that ursolic
      acid induced the expression of osteoblast-specific genes with the activation of
      mitogen-activated protein kinases, nuclear factor-kappaB, and activator protein
      1. Additionally, noggin, an antagonist of bone morphogenetic proteins (BMPs),
      inhibited ursolic acid-induced osteoblast differentiation. Noggin also inhibited
      the activation of Smad and the induction of BMP-2 mRNA expression by ursolic acid
      in the late stage of osteoblast differentiation. Importantly, ursolic acid was
      shown to have bone-forming activity in vivo in a mouse calvarial bone formation
      model. A high proportion of positive immunostaining of BMP-2 was found in the
      nuclear region of woven bone formed by ursolic acid. These results suggested that
      ursolic acid has the anabolic potential to stimulate osteoblast differentiation
      and enhance new bone formation.

PMID- 18822380
TI  - NR4A2 controls the differentiation of selective dopaminergic nuclei in the
      zebrafish brain.
AB  - The orphan nuclear receptor NR4A2/Nurr1 is mandatory for the terminal
      differentiation of mesencephalic dopamine neurons in mammals, but a similar role
      has remained elusive in the homologous area of the fish brain, the posterior
      tuberculum. Using loss- and gain-of-function experiments in zebrafish, we show
      that NR4A2 is indeed responsible for the expression of tyrosine hydroxylase (TH)
      in selective subpopulations of dopamine cells in the posterior tuberculum, as
      well as in the pretectum, preoptic area and telencephalon. Cross sections of the
      neural tube reveal that cells expressing the proliferation marker PCNA, NR4A2 and
      TH are aligned along a mediolateral progression rather than overlapping
      populations, suggesting that NR4A2 does not simply regulate TH expression but
      also controls more general steps of progenitor commitment towards the fully
      differentiated DA neuronal state. Finally, in line with NR4A2+/- heterozygote
      mice, NR4A2 morphant fish are hyperactive. This behavioural phenotype is
      maintained throughout life, pointing to a developmental control of locomotor
      activity by NR4A2. Our results shed new light on NR4A2 function in the DA
      differentiation pathway, and stress the effect of DA dysregulation on the control
      of locomotor activity.

PMID- 18822381
TI  - Cape diversification and repeated out-of-southern-Africa dispersal in paper
      daisies (Asteraceae-Gnaphalieae).
AB  - The large daisy tribe Gnaphalieae occurs in extra-tropical habitats worldwide,
      but is most diverse in southern Africa and in Australia. We explore the age and
      evolutionary history of the tribe by means of a phylogenetic hypothesis based on
      Bayesian analysis of plastid and nuclear DNA sequences, maximum likelihood
      reconstruction of ancestral areas, and relaxed Bayesian dating. Early
      diversification occurred in southern Africa in the Eocene-Oligocene, resulting in
      a grade of mostly Cape-centred lineages which subsequently began speciating in
      the Miocene, consistent with diversification times for many Cape groups.
      Gnaphalieae from other geographic regions are embedded within a southern African
      paraphylum, indicating multiple dispersals out of southern Africa since the
      Oligocene to Miocene which established the tribe in the rest of the world.
      Colonisation of Australia via direct long-distance trans-oceanic dispersal in the
      Miocene resulted in the radiation which produced the Australasian gnaphalioid
      flora. The similarly diverse regional gnaphalioid floras of Australasia and
      southern Africa thus exhibit very different temporal species accumulation
      histories. An examination of the timing and direction of trans-Indian Ocean
      dispersal events in other angiosperms suggests a role for the West Wind Drift in
      long-distance dispersal eastwards from southern Africa.

PMID- 18822382
TI  - Effects of environmental salinity on gill endothelin receptor expression in the
      killifish, Fundulus heteroclitus.
AB  - We recently determined that rapid changes in environmental salinity alter
      endothelin-1 (EDN1) mRNA levels in the euryhaline killifish, Fundulus
      heteroclitus, so we hypothesized that EDN1 may be a local regulator of gill ion
      transport in teleost fishes. The purpose of the present study was to examine the
      effects of changes in environmental salinity on the gill endothelin receptors:
      EDNRA, EDNRB, and EDNRC. Using quantitative real-time PCR, we determined that
      after a fresh water (FW) to seawater (SW) transfer, there is a two to threefold
      increase in gill EDNRA and EDNRB mRNA levels. Likewise, we found a two to three
      fold increase in gill EDNRA and EDNRB protein concentration. In addition,
      killifish that have acclimated to FW for 30 days had significantly lower EDNRA
      mRNA and protein levels than SW killifish. ENDRA were immunolocalized to the
      mitochondrion-rich cells of the killifish gill, suggesting that EDN1 signaling
      cascades may affect MRC function. EDNRB were found throughout the gill
      vasculature and on lamellar pillar cells. We previously immunolocalized EDN1 to
      the pillar cell suggesting that EDN1 acts as an autocrine signaling molecule and
      potentially regulates pillar cell tone and lamellar perfusion. We conclude that
      EDN1 is physiologically active in the teleost gill, and regulated by
      environmental salinity. Future functional studies examining the physiological
      role of this system are necessary to completely understand EDN1 in the fish gill.

PMID- 18822383
TI  - Apolipophorin III from Hyphantria cunea shows different anti-oxidant ability
      against LDL oxidation in the lipid-free and lipid-bound state.
AB  - Insect apolipophorin III (apoLp-III) and human apolipoprotein A-I (apoA-I) are
      major protein constituents of the lipoprotein system that share various
      properties. In order to compare the anti-oxidant ability of apoLp-III and apoA-I
      in the lipid-free and lipid-bound state, both proteins were purified and
      synthesized individually as a palmitoyloleoyl phosphatidylcholine (POPC)
      reconstituted high-density lipoprotein (rHDL) using the same molar ratio. In the
      lipid-bound state, apoLp-III and apoA-I showed good anti-oxidant activities
      against copper-mediated LDL oxidation. Furthermore, apoLp-III and apoA-I, in the
      lipid-bound state, exhibited potent activities in ferric ion-reducing ability
      (FRA). However, lipid-free apoLp-III lost the anti-oxidant activity and FRA
      ability in contrast to lipid-free apoA-I. Lipid-free apoA-I treatment prevented
      the cellular uptake of oxLDL in macrophages, as visualized by oil-red O staining
      and detection assays for malondialdehyde (MDA) and lipid hydroperoxide (LPO) in
      the culture media. However, lipid-free apoLp-III did not prevent the uptake of
      oxLDL. These results indicate that the putative conformational change of apoLp
      III during lipid association is critical for the maintenance of anti-oxidant
      activity and that the physiologic role of apoLp-III may differ when it is in the
      lipid-free state and the lipid-bound state.

PMID- 18822384
TI  - Tumor suppressor SMAR1 downregulates Cytokeratin 8 expression by displacing p53
      from its cognate site.
AB  - Intermediary filaments play a crucial role in transformation of cells to a
      malignant phenotype. Here, we report that tumor suppressor SMAR1 downregulates
      Cytokeratin 8 gene expression by modulating p53-mediated transactivation of this
      gene. Moreover, the cell surface cytokeratin expression was downregulated leading
      to a decreased migration and invasiveness of cells. We further validated these
      results using genotoxic stress agents that lead to an increase in the levels of
      SMAR1 protein. This subsequently represses the transcription of Cytokeratin 8
      gene by local chromatin condensation mediated by histone methylation and
      deacetylation. Evaluation of SMAR1 and Cytokeratin 8 proteins in different grades
      of cancer using tissue microarray point out at the inverse expression profiles of
      these genes (i.e. low levels of SMAR1 correlating with high expression of
      Cytokeratin 8) in higher grades of breast cancer. Therefore, the results
      presented here highlight the mechanism of Cytokeratin 8 gene regulation by
      interplay of tumor suppressor proteins SMAR1 and p53.

PMID- 18822385
TI  - PPARgamma agonists attenuate proliferation and modulate Wnt/beta-catenin
      signalling in melanoma cells.
AB  - Peroxisome proliferator-activated receptor-gamma (PPARgamma) is a member of the
      nuclear hormone receptor (NHR) superfamily of ligand-activated transcriptional
      regulators. Accumulating evidence suggests that PPARgamma agonists such as the
      thiazolidinediones (TZDs) may prove to be useful anti-cancer agents exhibiting
      anti-proliferative and/or pro-apoptotic affects in a range of cancer cell types
      including melanoma, however, the mechanisms underlying this effect remain
      unclear. We have demonstrated the anti-proliferative effects of full and partial
      PPARgamma modulators in human melanoma cell lines. Ablation of PPARgamma
      expression in the MM96L melanoma cell line by siRNA mediated mechanisms
      attenuates the anti-proliferative effect of these agents suggesting this effect
      is directly mediated by PPARgamma. The mechanisms underlying the anti
      proliferative effects of PPARgamma in melanoma cells involve the regulation of
      expression of a number of critical cell cycle genes and beta-catenin. Moreover,
      our data indicate that PPARgamma modulates Wnt/beta-catenin mediated signalling
      in melanoma cells in an agonist dependent manner.

PMID- 18822386
TI  - Population genomics: diversity and virulence in the Neisseria.
AB  - Advances in high-throughput nucleotide sequencing and bioinformatics make the
      study of genomes at the population level feasible. Preliminary population genomic
      studies have explored the relationships among three closely related bacteria,
      Neisseria meningitidis, Neisseria gonorrhoeae and Neisseria lactamica, which
      exhibit very different phenotypes with respect to human colonisation. The data
      obtained have been especially valuable in the establishing of the role of
      horizontal genetic exchange in bacterial speciation and shaping population
      structure. In the meningococcus, they have been used to define invasive genetic
      types, search for virulence factors and potential vaccine components and
      investigate the effects of vaccines on population structure. These are generic
      approaches and their application to the Neisseria provides a foretaste for their
      application to the wider bacterial world.

PMID- 18822387
TI  - Low hanging fruit in infectious disease drug development.
AB  - Cost estimates for developing new molecular entities (NME) are reaching non
      sustainable levels and coupled with increasing regulatory requirements and
      oversight have led many pharmaceutical sponsors to divest their anti-microbial
      development portfolios [Projan SJ: Why is big Pharma getting out of anti
      bacterial drug discovery?Curr Opin Microbiol 2003, 6:427-430] [Spellberg B,
      Powers JH, Brass EP, Miller LG, Edwards JE, Jr: Trends in antimicrobial drug
      development: implications for the future.Clin Infect Dis 2004, 38:1279-1286].
      Operational issues such as study planning and execution are significant
      contributors to the overall cost of drug development that can benefit from the
      leveraging of pre-randomization data in an evidence-based approach to protocol
      development, site selection and patient recruitment. For non-NME products there
      is even greater benefit from available data resources since these data may permit
      smaller and shorter study programs. There are now many available open source
      intelligence (OSINT) resources that are being integrated into drug development
      programs, permitting an evidence-based or 'operational epidemiology' approach to
      study planning and execution.

PMID- 18822388
TI  - Virogenomics: the virus-host interaction revisited.
AB  - Genomics tools allow us to assess gene expression 'genome wide' providing an
      unprecedented view on the host-side of the virus-host interaction. The success of
      the application of these tools crucially depends on our ability to reduce the
      total information load while increasing the information density of the data
      collected. In addition to the advanced data analysis algorithms, gene annotation
      pathway databases, and theoretical models, specifically designed sets of
      complementary experiments are crucial in translating the collected genomics data
      into palatable knowledge. A better understanding of the molecular basis of virus
      host interactions will support the rational design of improved and novel
      intervention strategies for viral infections.

PMID- 18822389
TI  - Development of the Gateway system for cloning and expressing genes in Entamoeba
      histolytica.
AB  - The early branching eukaryote Entamoeba histolytica is a human parasite that is
      the etiologic agent of amebic dysentery and liver abscess. The sequencing of the
      E. histolytica genome combined with the development of an E. histolytica
      microarray has resulted in the identification of several distinct gene expression
      profiles associated with virulence. The function of many modulated transcripts is
      unknown and their role in pathogenicity is unclear. They however represent a pool
      of potential virulence factors that could be targets for the development of novel
      therapeutics. Efficient tools and methods to characterize these novel virulence
      associated genes and proteins would be beneficial. Here we report the use of the
      Gateway((R)) cloning system to generate the E. histolytica expression vector pAH
      DEST. To test the usefulness of this system, the vector was used to construct a
      plasmid containing a recombinant version of the locus EHI_144490, which encoded a
      protein of unknown function. The recombinant gene was expressed and the
      recombinant protein, which was strep-myc-tagged, showed a cytoplasmic
      localization in transfected trophozoites. This expression vector with the
      Gateway((R)) system should facilitate investigation into the functions of novel
      proteins in E. histolytica.

PMID- 18822390
TI  - Response to the letter of Dr. Ming-Hua Zheng and colleagues on "Recombination
      human hepatocyte growth factor for liver failure".

PMID- 18822391
TI  - Induction of late airway response was involved in serum antigen-specific
      immunoglobulin G in rats.
AB  - The antigen-induced immediate airway response (IAR) has been considered a form of
      bronchoconstriction mainly provoked by histamine and leukotriene C4/D4/E4, which
      are released by stimulation by antigen-specific IgE. However, the
      pathophysiological features of the antigen-induced late airway response (LAR) are
      not yet fully understood. In the present study, sensitized rats were repeatedly
      exposed to ovalbumin (OVA) to induce IAR and LAR, and the immunological profiles
      of IAR and LAR were examined. The first antigen inhalation induced only IAR but
      not LAR. However, the second antigen inhalation 7 days after IAR induced LAR but
      not IAR. Tumor necrosis factor (TNF)-alpha level in BALF in LAR was significantly
      higher than that in IAR, although there were no differences in histamine,
      leukotriene C4/D4/E4, interleukin (IL)-1beta, or IL-13 levels between IAR and
      LAR. Serum antigen-specific IgE titer was high in both IAR and LAR, but serum
      antigen-specific IgG, IgG1, and IgG2a titers were dramatically high in LAR but
      not IAR. There were significant correlations between antigen-specific IgG, IgG1,
      and IgG2a titers and LAR. Interestingly, LAR could be induced in normal rats by
      transfer of serum from LAR rats, which exhibited high antigen-specific IgG, IgG1,
      and IgG2a titers. In conclusion, these findings suggest that repeated antigen
      inhalation converts IAR to LAR, and that LAR is a reaction triggered by antigen
      specific IgG and involving TNF-alpha. This is the first study to directly suggest
      the involvement of antigen-specific IgG in the induction of LAR.

PMID- 18822392
TI  - Mammalian SWI/SNF chromatin remodeling complexes are required to prevent
      apoptosis after DNA damage.
AB  - Although SWI/SNF chromatin remodeling complexes play important roles in
      transcription, recent studies suggest that they also participate directly in DNA
      repair. In yeast, SWI/SNF and related RSC complexes have been shown to be
      recruited to the sites of DNA double strand breaks (DSBs) to facilitate DNA
      repair. We recently have shown that mammalian SWI/SNF complexes contribute to DBS
      repair by direct mechanisms of stimulating the phosphorylation of histone H2AX at
      DSB-surrounding chromatin. Here we investigated the role of mammalian SWI/SNF
      complexes in cell survival after DNA damage. When SWI/SNF was inactivated by
      means of dominant negativity or its catalytic subunit BRG1 was knockdowned by
      small interfering RNA, cells became highly susceptible to DNA damage-induced
      apoptosis. SWI/SNF inactivation had no effect on the activation and establishment
      of G2/M DNA damage checkpoint. However, SWI/SNF-defective cells could not sustain
      the G2/M checkpoint long enough to survive DNA damage, and rather underwent
      apoptosis before entering mitosis. We also found that, although the basal state
      and DNA damage-triggered activation of p53 were normal, the kinetics of p53
      downregulation was significantly delayed in SWI/SNF-defective cells. Finally, the
      sustained p53 activation in SWI/SNF-defective cells was accompanied by
      accumulation of unrepaired DSBs owing to inefficient DNA repair. These results
      suggest that mammalian SWI/SNF complexes prevent DNA damage-induced apoptosis in
      part by facilitating efficient repair and thereby ensuring timely elimination of
      unrepaired DSBs that could otherwise lead to excessive prolongation of p53
      activation.

PMID- 18822393
TI  - Aestivation in the South American lungfish, Lepidosiren paradoxa: effects on
      cardiovascular function, blood gases, osmolality and leptin levels.
AB  - The African (Protopterus sp.) and South American lungfish (Lepidosiren paradoxa)
      inhabit shallow waters, that seasonally dry out, which induces aestivation and
      cocoon formation in Protopterus. Differently, L. paradoxa has no cocoon, and it
      aestivates in a simple burrow. In water PaCO(2) is 21.8+/-0.4mmHg (mean values+/
      S.E.M.; n=5), whereas aestivation for 20 days increased PaCO(2) to as much as
      37.6+/-2.1mmHg, which remained the same after 40 days (35.8+/-3.3mmHg).
      Concomitantly, the plasma [HCO(3)(-)]-values for animals in water were 22.5+/
      0.5mM, which after 20 days increased to 40.2+/-2.3mM and after 40 days to 35.8+/
      3.3mM. Initially in water, PaO(2) was 87.7+/-2.0mmHg, but 20 days in aestivation
      reduced the value to 80.5+/-2.2 and later (40 days) to 77.1+/-3.0mmHg. Meanwhile,
      aestivation had no effect on pHa and hematocrit. The blood pressures were equal
      for animals in the water or in the burrow (P(mean) approximately 30mmHg), and
      cardiac frequency (f(H)) fell from 31beats min(-1) to 22beats min(-1) during 40
      days of aestivation. The osmolality (mOsmkgH(2)O(-1)) was elevated after 20 and
      40 days of aestivation but declined upon return to water. The transition from
      activity to aestivation involves new set-points for the variables that determine
      the acid-base status and PaO(2) of the animals, along with a reduction of cardiac
      frequency.

PMID- 18822394
TI  - Role of TRP channels and NCX in mediating hypoxia-induced [Ca(2+)](i) elevation
      in PC12 cells.
AB  - Mammalian cells require a constant O2 supply to produce adequate energy, and
      sustained hypoxia can kill cells. Mammals therefore have evolved sophisticated
      mechanisms to allow their cells to adapt to hypoxia. In this study, we
      investigated the role of TRP channels and the Na+-Ca2+ exchanger (NCX) in
      mediating hypoxia-induced [Ca2+]i elevation in a model of the O2-sensing rat
      pheochromocytoma (PC12) cell line by using Ca2+ imaging and molecular biological
      approaches. Non-selective cation channels, such as TRPC1, 3 and 6, were found to
      be functionally expressed in PC12 cells. They mediated Ca2+ entry when cells were
      exposed to acute hypoxia (PO2 of 15 mmHg), in addition to Ca2+ entry via VGCCs.
      Blockage of TRPCs by 2APB and SKF96365 could significantly reduce hypoxia
      mediated [Ca2+]i elevation. Suramin and U73122 attenuated the hypoxia-induced
      [Ca2+]i elevation, implying the involvement of the G-protein and PLC pathways in
      the hypoxic response. In addition to TRPCs and VGCCs, NCX also contributed to the
      hypoxia-induced [Ca2+]i elevation, and blockade of NCX by KBR7943 could
      significantly decrease the hypoxia-induced [Ca2+]i elevation. Our results suggest
      that the activation of TRP by hypoxia could lead to NCX reversal; furthermore,
      membrane depolarization and TRPCs may play a primary role in mediating the
      hypoxic response in PC12 cells.

PMID- 18822395
TI  - Investigation of a role for Glu-331 and Glu-305 in substrate binding of
      tripeptidyl-peptidase II.
AB  - The aim of this study was to investigate the mechanism by which tripeptidyl
      peptidase II (TPP II) can specifically release tripeptides from the free N
      terminus of an oligopeptide. The subtilisin-like N-terminal part of TPP II was
      modelled using subtilisin as template. Two glutamate residues (Glu-305 and Glu
      331) appeared to be positioned so as to interact with the positively charged N
      terminus of the substrate. In order to test this potential interaction, both
      residues were replaced by glutamine and lysine. The catalytic efficiency was
      reduced 400-fold for the E331Q variant and 20000-fold for the E331K variant,
      compared with the wild-type (wt). A substantial part of this reduction was due to
      decreased substrate affinity, since the K(M) for both mutants was at least two
      orders of magnitude greater than for the wt. This decrease was linked
      specifically to interaction with the free N-terminal amino group, based on
      inhibition studies. Glu-305 appears to be essential for enzymatic activity, but
      the extremely low activity of the E305Q variant prevented an investigation of the
      involvement of Glu-305 in substrate binding. The present work is, to our
      knowledge, the first report to investigate a mechanism for a tripeptidyl
      peptidase activity through site-directed mutagenesis.

PMID- 18822396
TI  - Deletion 2q36.2q36.3 with multiple renal cysts and severe mental retardation.
AB  - Interstitial 2q36 deletion is a rare event. We report on a patient with a de novo
      del(2)(q36.2q36.3) interstitial deletion of the long arm of chromosome 2
      diagnosed by classical banding. The phenotype comprised facial dysmorphism,
      enlarged kidneys with multiple renal cysts, abnormal minora labia, asymmetric
      lower limbs with dysplastic patella, and severe mental retardation. By physical
      mapping, using array-comparative genomic hybridisation (CGH) confirmed by
      Fluorescent In Situ Hybridisation (FISH), the breakpoints of the deletion were
      mapped and the size of the deletions was measured: 5.61+/-0.19Mb. A skin biopsy
      was analysed using electronic microscopy showing an alteration of the structure
      and organisation of the dermal and peri-neuronal basement membrane. The relation
      between the phenotype and the deletion of both COL4A4 and COL4A3 genes, located
      in 2q36.3 loci, as well as the disruption of TRIP12 were discussed.

PMID- 18822397
TI  - Conserved properties of a urochordate estrogen receptor-related receptor (ERR)
      with mammalian ERRalpha.
AB  - Estrogen receptor-related receptors (ERRs) were the first orphan nuclear
      receptors identified on the basis of their sequence similarity to the estrogen
      receptors. Although unique ERRs were found in some marine invertebrates, the
      molecular functions of these receptors are not well understood. In the present
      study, we identified three transcript variants of the tunicate Halocynthia
      roretzi ERR (Hr-ERR), varying in their 3' untranslated regions, and putatively
      encoding a unique receptor deriving from an ancestor protein common to vertebrate
      ERRalpha/beta/gamma. Maternal mRNA of Hr-ERR was detected throughout the entire
      egg cytoplasm and early embryos. Zygotic Hr-ERR was predominantly expressed in
      the heart, and at lower levels in muscle, stomach, gonad and digestive glands.
      Electrophoretic mobility shift assay demonstrated that Hr-ERR directly binds to
      the estrogen-response element (ERE) and ERR-response element (ERRE). Gene
      reporter assays also showed that Hr-ERR activates transcription through ERE and
      ERRE. Hr-ERR-mediated transactivation was modulated by various cofactors for
      mammalian ERRs, such as peroxisome proliferator-activated receptor gamma
      coactivator 1-alpha and small heterodimer partner. In addition, the ERR
      antagonists 4-hydroxytamoxifen and diethylstilbestrol inhibited the Hr-ERR
      mediated transactivation, whereas Hr-ERR activity on ERE was further induced by
      genistein, an ERRalpha agonist. Taken together, our results show that Hr-ERR is
      an unduplicated ERR that however, possesses functional properties common to
      ERRalpha and not to ERRbeta/gamma.

PMID- 18822399
TI  - Comparison of intact tissues and isolated cells from human fetal membranes.

PMID- 18822398
TI  - Specimen size and porosity can introduce error into microCT-based tissue mineral
      density measurements.
AB  - The accurate measurement of tissue mineral density, rho(m), in specimens of
      unequal size or quantities of bone mineral using polychromatic microCT systems is
      important, since studies often compare samples with a range of sizes and bone
      densities. We assessed the influence of object size on microCT measurements of
      rho(m) using (1) hydroxyapatite rods (HA), (2) precision-manufactured aluminum
      foams (AL) simulating trabecular bone structure, and (3) bovine cortical bone
      cubes (BCt). Two beam-hardening correction (BHC) algorithms, determined using a
      200 and 1200 mg/cm(3) HA wedge phantom, were used to calculate rho(m) of the HA
      and BCt. The 200 mg/cm(3) and an aluminum BHC algorithm were used to calculate
      the linear attenuation coefficients of the AL foams. Equivalent rho(m)
      measurements of 500, 1000, and 1500 mg HA/cm(3) rods decreased (r(2)>0.96, p<0.05
      for all) as HA rod diameter increased in the 200 mg/cm(3) BHC data. Errors
      averaged 8.2% across these samples and reached as high as 29.5%. Regression
      analyses suggested no size effects in the 1200 mg/cm(3) BHC data but differences
      between successive sizes still reached as high as 13%. The linear attenuation
      coefficients of the AL foams increased up to approximately 6% with increasing
      volume fractions (r(2)>0.81, p<0.05 for all) but the strength of the size-related
      error was also BHC dependent. Equivalent rho(m) values were inversely correlated
      with BCt cube size (r(2)>0.92, p<0.05). Use of the 1200 mg/cm(3) BHC ameliorated
      the size-related artifact compared to the 200 mg/cm(3) BHC but errors with this
      BHC were still significant and ranged between 5% and 12%. These results
      demonstrate that object size, structure, and BHC algorithm can influence microCT
      measurements of rho(m). Measurements of rho(m) of specimens of unequal size or
      quantities of bone mineral must be interpreted with caution unless appropriate
      steps are taken to minimize these potential artifacts.

PMID- 18822400
TI  - Preeclampsia and subsequent risk of cancer: update from the Jerusalem Perinatal
      Study.
AB  - OBJECTIVE: The purpose of this study was to examine the association between
      preeclampsia and cancer incidence. STUDY DESIGN: The Jerusalem Perinatal Study is
      a population-based cohort of all births to 41,206 residents of Western Jerusalem
      from 1964-76. Cancer incidence to 2004 was assessed by linkage of the cohort with
      the Israel Cancer Registry. Cox's proportional hazards models were constructed to
      estimate the hazard ratio for cancer among women who had had preeclampsia.
      RESULTS: Preeclampsia was associated with a 1.23-fold increased risk of cancer at
      all sites, a 37% increased risk of breast cancer, and more than a doubling of
      ovarian cancer risk. Analysis by morphologic condition yielded significantly
      increased risks for malignancies that were classed as cystic mucinous and serous
      (relative risk, 1.96; 95% CI, 1.00-3.83) and for ductal, lobular, and medullary
      carcinomas (relative risk, 1.40; 95% CI, 1.07-1.83). No differential association
      was observed by sex of offspring. CONCLUSION: Our study suggests that the
      previously described protective effect of preeclampsia on cancer is not
      universal.

PMID- 18822402
TI  - Y chromosome azoospermia factor region microdeletions and recurrent pregnancy
      loss.
AB  - OBJECTIVE: This study was undertaken to determine the prevalence of Y-chromosome
      microdeletions in couples with recurrent pregnancy loss (RPL) as compared with
      fertile couples. STUDY DESIGN: Forty-three men from couples with recurrent
      pregnancy loss, and 43 men from couples with a live birth and no history of
      miscarriages were recruited from Zekai Tahir Burak Woman Health, Education and
      Research Hospital. The DNA was tested for the presence of 4 sequence tagged sites
      (STSs) spanning 4 AZF regions: DYS220 (AZFb), DYS235, DYS236, and DYS237 (AZFd).
      RESULTS: Seven (7) of the 43 men (16%) from couples with recurrent pregnancy loss
      had microdeletions in 1 or more of the 4 segments studied, whereas none of the
      fertile men had any microdeletions (P < .05). Their microdeletions were all found
      specifically at locus DYS 220 (AZFb). CONCLUSION: The prevalence of the Y
      chromosome microdeletion in AZF region was much higher in men from couples with
      recurrent pregnancy loss than men in fertile couples. This study showed that Y
      chromosome microdeletion in AZF region may be a possible etiologic factor of
      recurrent pregnancy loss.

PMID- 18822401
TI  - Can a prediction model for vaginal birth after cesarean also predict the
      probability of morbidity related to a trial of labor?
AB  - OBJECTIVE: The objective of the study was to determine whether a model for
      predicting vaginal birth after cesarean (VBAC) can also predict the probabilty of
      morbidity associated with a trial of labor (TOL). STUDY DESIGN: Using a
      previously published prediction model, we categorized women with 1 prior cesarean
      by chance of VBAC. Prevalence of maternal and neonatal morbidity was stratfied by
      probability of VBAC success and delivery approach. RESULTS: Morbidity became less
      frequent as the predicted chance of VBAC increased among women who underwent TOL
      (P < .001) but not elective repeat cesarean section (ERCS) (P > .05). When the
      predicted chance of VBAC was less than 70%, women undergoing a TOL were more
      likely to have maternal morbidity (relative risk [RR], 2.2; 95% confidence
      interval [CI], 1.5-3.1) than those who underwent an ERCS; when the predicted
      chance of VBAC was at least 70%, total maternal morbidity was not different
      between the 2 groups (RR, 0.8; 95% CI, 0.5-1.2). The results were similar for
      neonatal morbidity. CONCLUSION: A prediction model for VBAC provides information
      regarding the chance of TOL-related morbidity and suggests that maternal
      morbidity is not greater for those women who undergo TOL than those who undergo
      ERCS if the chance of VBAC is at least 70%.

PMID- 18822403
TI  - Forced coughing versus local anesthesia and pain associated with cervical biopsy:
      a randomized trial.
AB  - OBJECTIVE: Cervical biopsy often causes discomfort and pain. To compare local
      anesthesia (1% lidocaine) with forced coughing as pain relief, we quantified the
      actual pain experienced during cervical punch biopsies. STUDY DESIGN: For a
      prospective trial conducted at the Medical University of Vienna, 68 women
      undergoing cervical punch biopsies for assessment of abnormal cervical smears
      were randomized in 2 pain relief treatment groups. Patients' discomfort was
      assessed immediately after taking the biopsy using at 10-cm visual analog scale.
      RESULTS: No statistically significant difference was found between pain scores
      recorded for the 2 groups (P = .47, 95% confidence interval [CI], -0.4 to 1.3
      cm). However, when local anesthesia was applied, the examination was
      significantly prolonged by a median of 2.11 min (P < .001; 95% CI, 1.6-2.8).
      CONCLUSION: Forced coughing during cervical biopsies reduces patients' discomfort
      to the same extent as local anesthesia, but is associated with a significantly
      reduced examination time.

PMID- 18822404
TI  - The effect of sleep deprivation on fine motor coordination in obstetrics and
      gynecology residents.
AB  - OBJECTIVE: The purpose of this study was to evaluate the effect of acute sleep
      deprivation on the fine motor coordination in obstetrics and gynecology
      residents. STUDY DESIGN: Twenty-eight obstetrics and gynecology residents
      completed a series of tasks using the Purdue pegboard standardized protocol for
      testing fine motor coordination both before and after a 24-hour call. RESULTS:
      Twenty-three participants were women and 5 were men. There was a learning curve
      demonstrated for performance of the tasks. There was a statistically significant
      decline in performance of residents after overnight call. When adjusting for the
      learning curve, effects of sleep deprivation were magnified for all tasks: right
      (dominant) hand (P = .0005), left hand (P = .0020), both hands (P < .0001), and
      assembly (P < .0001). There were significant differences in performance when
      segregated by year of training and sex; female residents appeared to tolerate
      better lack of sleep. CONCLUSION: Acute sleep deprivation has a deleterious
      effect on fine motor coordination in this group of obstetrics and gynecology
      residents.

PMID- 18822405
TI  - [Outpatient tonsillectomy in children].
AB  - Tonsillectomy may be performed as an outpatient procedure because post
      tonsillectomy hemorrhages occur during the first few hours, and therefore are
      diagnosed before discharge, or occur after the sixth day. Nevertheless, not all
      patients are eligible for outpatient tonsillectomy. Both the ENT surgeon and the
      anesthesiologist must identify children who cannot be operated as outpatients
      because they do not satisfy the social criteria for discharge on the day of
      surgery (their parents do not speak French, they live too far from the hospital,
      etc.) or because they have individual risk factors for complications unrelated to
      their tonsils, such as bleeding disorders or related to their tonsils, such as a
      history of obstructive sleep apnea due to enlarged tonsils, particularly for
      young children. The anesthetic protocol must minimize the risk of postoperative
      nausea and vomiting. After tonsillectomy, the child may be discharged from the
      recovery room if he is fully awake, with no dyspnea and no oral bleeding, and is
      able to swallow liquids, without repeated vomiting.

PMID- 18822406
TI  - Increased expression of Annexin A2 in oral squamous cell carcinoma.
AB  - Previously, in vitro cellular carcinogenesis model of oral squamous cell
      carcinoma (OSCC) was established with a line of human immortalized oral epithelia
      cells (HIOECs), a line of cancerous HB96 cells, and another kind of cells (HB56
      cells) at the early stage of carcinogenesis. In this study, comparative proteomic
      analysis identified a panel of differentially expressed proteins among these
      cells, and Annexin A2 shown as one of the significantly up-regulated proteins
      accompanying cellular transformation. Annexin A2 was further validated for its
      expression in the three kinds of cells and in the clinical samples of tumour
      tissues and their adjacent normal epithelia from primary OSCC patients. Western
      blot analysis and real-time PCR detected increased Annexin A2 protein and mRNA
      levels in cancerous HB56 and HB96 cells over HIOECs. Immunohistochemistry showed
      elevated Annexin A2 protein expression in tumour tissues over the adjacent non
      malignant epithelia from OSCC patients; however, the mRNA levels between tumour
      and normal tissues did not change significantly. Interestingly, levels of Annexin
      A2 protein expression negatively correlated with the tumour differentiation
      grades. The results presented here suggest that Annexin A2 protein may play
      important roles in carcinogenesis of OSCC, and it may also serve as a candidate
      biomarker for pathologic differentiation grade of OSCC.

PMID- 18822407
TI  - Multivariate pattern analysis of functional magnetic resonance imaging data
      reveals deficits in distributed representations in schizophrenia.
AB  - BACKGROUND: Multivariate pattern analysis is an alternative method of analyzing
      functional magnetic resonance imaging (fMRI) data, which is capable of decoding
      distributed neural representations. We applied this method to test the hypothesis
      of the impairment in distributed representations in schizophrenia. We also
      compared the results of this method with traditional general linear model (GLM)
      based univariate analysis. METHODS: Nineteen schizophrenia and 15 control
      subjects viewed two runs of stimuli-exemplars of faces, scenes, objects, and
      scrambled images. To verify engagement with stimuli, subjects completed a 1-back
      matching task. A multivoxel pattern classifier was trained to identify category
      specific activity patterns on one run of fMRI data. Classification testing was
      conducted on the remaining run. Correlation of voxelwise activity across runs
      evaluated variance over time in activity patterns. RESULTS: Patients performed
      the task less accurately. This group difference was reflected in the pattern
      analysis results with diminished classification accuracy in patients compared
      with control subjects, 59% and 72%, respectively. In contrast, there was no group
      difference in GLM-based univariate measures. In both groups, classification
      accuracy was significantly correlated with behavioral measures. Both groups
      showed highly significant correlation between interrun correlations and
      classification accuracy. CONCLUSIONS: Distributed representations of visual
      objects are impaired in schizophrenia. This impairment is correlated with
      diminished task performance, suggesting that decreased integrity of cortical
      activity patterns is reflected in impaired behavior. Comparisons with univariate
      results suggest greater sensitivity of pattern analysis in detecting group
      differences in neural activity and reduced likelihood of nonspecific factors
      driving these results.

PMID- 18822408
TI  - Increased anterior cingulate cortical activity in response to fearful faces: a
      neurophysiological biomarker that predicts rapid antidepressant response to
      ketamine.
AB  - BACKGROUND: Most patients with major depressive disorder (MDD) experience a
      period of lengthy trial and error when trying to find optimal antidepressant
      treatment; identifying biomarkers that could predict response to antidepressant
      treatment would be of enormous benefit. We tested the hypothesis that
      pretreatment anterior cingulate cortex (ACC) activity could be a putative
      biomarker of rapid antidepressant response to ketamine, in line with previous
      findings that investigated the effects of conventional antidepressants. We also
      investigated patterns of ACC activity to rapid presentation of fearful faces
      compared with the normal habituation observed in healthy subjects. METHODS: We
      elicited ACC activity in drug-free patients with MDD (n = 11) and healthy control
      subjects (n = 11) by rapidly presenting fearful faces, a paradigm known to
      activate rostral regions of the ACC. Spatial-filtering analyses were performed on
      magnetoencephalographic (MEG) recordings, which offer the temporal precision
      necessary to estimate ACC activity elicited by the rapid presentation of stimuli.
      Magnetoencephalographic recordings were obtained only once for both patients and
      control subjects. Patients were subsequently administered a single ketamine
      infusion followed by assessment of depressive symptoms 4 hours later. RESULTS:
      Although healthy subjects had decreased neuromagnetic activity in the rostral ACC
      across repeated exposures, patients with MDD showed robust increases in
      pretreatment ACC activity. Notably, this increase was positively correlated with
      subsequent rapid antidepressant response to ketamine. Exploratory analyses showed
      that pretreatment amygdala activity was negatively correlated with change in
      depressive symptoms. CONCLUSIONS: Pretreatment rostral ACC activation may be a
      useful biomarker that identifies a subgroup of patients who will respond
      favorably to ketamine's antidepressant effects.

PMID- 18822409
TI  - Structural elucidation of a cell wall fungal polysaccharide isolated from
      Ustilaginoidea virens, a pathogenic fungus of Oriza sativa and Zea mays.
AB  - The alkali-extractable water-soluble polysaccharides (F1SS) isolated from the
      outer cell wall of two strains of Ustilaginoidea virens have been studied by
      chemical and methylation analyses, and 1D and 2D (1)H and (13)C NMR spectroscopy.
      The structures of these polysaccharides are very similar, and can be described by
      the following idealized repeating unit: where n and m are approximately 1 and 2,
      respectively.

PMID- 18822410
TI  - A thixotropic hydrogel from chemically cross-linked guar gum: synthesis,
      characterization and rheological behaviour.
AB  - Polysaccharide guar gum (GG) was cross-linked in an alkaline solution with
      polyethylene glycol diglycidyl ether (PEGDGE) to create a new hydrogel. The GG
      hydrogel was examined by FT-IR spectroscopy, AFM analysis and SEM analysis. The
      water uptake of the GG hydrogel was measured at different pHs, and rheological
      studies were performed to verify the thixotropic nature of the material.
      Rheological studies revealed the pseudoplastic behaviour of the GG hydrogel and
      its thixotropic nature. AFM analysis on a sample which was subjected to shear
      stress showed the presence of nanoparticles in the hydrogel. When the sample was
      left to settle, the gel surface returned to its original homogenous morphology.
      The thixotropic and injectable nature of the GG hydrogel suggest its possible use
      in biomedical applications.

PMID- 18822411
TI  - Structure of the high-molecular weight exopolysaccharide isolated from
      Lactobacillus pentosus LPS26.
AB  - The strain Lactobacillus pentosus LPS26 produces a capsular polymer composed of a
      high- (2.0x10(6)Da) (EPS A) and a low-molecular mass (2.4x10(4)Da) (EPS B)
      polysaccharide when grown on semi-defined medium containing glucose as the carbon
      source. The structure of EPS A and its deacetylated form has been determined by
      monosaccharide and methylation analysis as well as by 1D/2D NMR studies ((1)H and
      (13)C). We conclude that EPS A is a charged heteropolymer, with a composition of
      D-glucose, D-glucuronic acid and L-rhamnose in a molar ratio 1:2:2. The repeating
      unit is a pentasaccharide with two O-acetyl groups at O-4 of the 3-substituted
      alpha-D-glucuronic acid and at O-2 of the 3-substituted beta-L-rhamnose,
      respectively. -->4)-alpha-D-Glcp-(1-->3)-alpha-D-GlcpA4Ac-(1-->3)-alpha-L-Rhap-(1
      ->4)-alpha-D-GlcpA-(1-->3)-beta-L-Rhap2Ac-(1--> This unbranched structure is not
      common in EPSs produced by Lactobacilli. Moreover, the presence of acetyl groups
      in the structure is an unusual feature which has only been reported in L. sake 0
      1 [Robijn et al. Carbohydr. Res., 1995, 276, 117-136].

PMID- 18822412
TI  - Design of new enzyme stabilizers inspired by glycosides of hyperthermophilic
      microorganisms.
AB  - In response to stressful conditions like supra-optimal salinity in the growth
      medium or temperature, many microorganisms accumulate low-molecular-mass organic
      compounds known as compatible solutes. In contrast with mesophiles that
      accumulate neutral or zwitterionic compounds, the solutes of hyperthermophiles
      are typically negatively charged. (2R)-2-(alpha-D-Mannopyranosyl)glycerate
      (herein abbreviated as mannosylglycerate) is one of the most widespread solutes
      among thermophilic and hyperthermophilic prokaryotes. In this work, several
      molecules chemically related to mannosylglycerate were synthesized, namely (2S)-2
      (1-O-alpha-D-mannopyranosyl)propionate, 2-(1-O-alpha-D-mannopyranosyl)acetate,
      (2R)-2-(1-O-alpha-D-glucopyranosyl)glycerate and 1-O-(2-glyceryl)-alpha-D
      mannopyranoside. The effectiveness of the newly synthesized compounds for the
      protection of model enzymes against heat-induced denaturation, aggregation and
      inactivation was evaluated, using differential scanning calorimetry, light
      scattering and measurements of residual activity. For comparison, the protection
      induced by natural compatible solutes, either neutral (e.g., trehalose, glycerol,
      ectoine) or negatively charged (di-myo-inositol-1,3'-phosphate and diglycerol
      phosphate), was assessed. Phosphate, sulfate, acetate and KCl were also included
      in the assays to rank the solutes and new compounds in the Hofmeister series. The
      data demonstrate the superiority of charged organic solutes as thermo-stabilizers
      of enzymes and strongly support the view that the extent of protein stabilization
      rendered by those solutes depends clearly on the specific solute/enzyme examined.
      The relevance of these findings to our knowledge on the mode of action of charged
      solutes is discussed.

PMID- 18822413
TI  - Effects of oral niacin on endothelial dysfunction in patients with coronary
      artery disease: results of the randomized, double-blind, placebo-controlled INEF
      study.
AB  - High-density-lipoproteins-cholesterol (HDL-C) is invertedly related to the
      incidence of cardiovascular events. Recent studies suggest that HDL-C directly
      improves endothelial function. Nicotinic acid (niacin) effectively raises serum
      HDL-C. We therefore hypothesized that treatment with niacin improves endothelial
      dysfunction in patients with coronary artery disease (CAD). One hundred seven
      patients with CAD were randomly assigned to double-blinded treatment for 12 weeks
      with extended-release (ER)-niacin 1000 mg/day (N) or placebo (C), respectively.
      Flow-mediated dilation (FMD) of the brachial artery, nitroglycerin-mediated
      endothelium-independent dilation (NMD) and serum lipid concentrations were
      measured before and after treatment. Triglycerides (P=0.013), low-density
      lipoprotein-cholesterol (LDL-C) (P=0.013) and HDL-C (P<0.0001) were altered by N
      compared to C. Niacin treatment was without effect on FMD or NMD, respectively,
      compared to placebo. However, post-hoc subgroup analysis revealed an improvement
      in FMD in patients with low HDL-C at baseline (absolute change in FMD (mean+/
      S.D.) N: +3.25+/-3.88%, C: +1.03+/-2.71% in low tertile HDL-C <or=45 mg/dl.
      P=0.047). The present findings indicate that ER-niacin treatment improves
      endothelial dysfunction in patients with CAD and low HDL-C, but not with normal
      HDL-C.

PMID- 18822414
TI  - Detection of occult coronary artery disease in asymptomatic individuals with
      diabetes mellitus using non-invasive cardiac angiography.
AB  - INTRODUCTION/OBJECTIVES: Cardiovascular disease is the leading cause of death for
      individuals with diabetes mellitus. Controversy exists regarding the screening of
      asymptomatic diabetics for occult coronary artery disease (CAD). The purpose of
      this study is to describe the prevalence of occult CAD in a group of asymptomatic
      subjects with diabetes using non-invasive coronary angiography, as well as to
      investigate the predictive accuracy of current guidelines with regards to their
      recommended criteria for further cardiac diagnostic testing in this patient
      population. METHODS: We prospectively enrolled 217 asymptomatic Korean
      outpatients with type 2 diabetes who had no prior history of CAD. All underwent
      non-invasive coronary angiography using a 64-slice multi-detector computed
      tomography scanner. RESULTS: The mean age of the study participants was 59+/-8
      years; 66% were men. Diabetes duration was 7+/-7 years, mean Framingham risk
      score was 13%, and mean hemoglobin A1C level was 7%. Of the 217 outpatients, 138
      (64%) had occult CAD based on cardiac computed tomography angiography (CCTA)
      findings. Thirty-six (36/138; 26%) had a significant stenosis on CCTA. Nearly
      half of the individuals (62/138; 45%) had a combination of non-calcified and
      calcified plaques. Only 5 out of 217 (2%) individuals with significant stenosis
      would have been missed using the American Diabetes Association (ADA) criteria for
      further cardiac testing. CONCLUSION: Almost two thirds of asymptomatic diabetics
      have occult CAD, including obstructive disease. Based on CCTA findings, the ADA
      criteria for further cardiac diagnostic testing would identify most individuals
      who have a significant coronary stenosis.

PMID- 18822415
TI  - Muscle contributions to support and progression over a range of walking speeds.
AB  - Muscles actuate walking by providing vertical support and forward progression of
      the mass center. To quantify muscle contributions to vertical support and forward
      progression (i.e., vertical and fore-aft accelerations of the mass center) over a
      range of walking speeds, three-dimensional muscle-actuated simulations of gait
      were generated and analyzed for eight subjects walking overground at very slow,
      slow, free, and fast speeds. We found that gluteus maximus, gluteus medius,
      vasti, hamstrings, gastrocnemius, and soleus were the primary contributors to
      support and progression at all speeds. With the exception of gluteus medius,
      contributions from these muscles generally increased with walking speed. During
      very slow and slow walking speeds, vertical support in early stance was primarily
      provided by a straighter limb, such that skeletal alignment, rather than muscles,
      provided resistance to gravity. When walking speed increased from slow to free,
      contributions to support from vasti and soleus increased dramatically. Greater
      stance-phase knee flexion during free and fast walking speeds caused increased
      vasti force, which provided support but also slowed progression, while
      contralateral soleus simultaneously provided increased propulsion. This study
      provides reference data for muscle contributions to support and progression over
      a wide range of walking speeds and highlights the importance of walking speed
      when evaluating muscle function.

PMID- 18822416
TI  - Development of an automated on-line pre-column derivatization procedure for
      sensitive determination of histamine in food with high-performance liquid
      chromatography-fluorescence detection.
AB  - An improved sensitive method was developed and validated for the determination of
      histamine in food samples by using automated on-line pre-column derivatization
      coupled with high performance liquid chromatography and fluorescence detection
      (HPLC-FLD). o-Phthaldialdehyde (OPA) was adopted as derivatization reagent, and a
      "sandwich" (OPA+histamine+OPA) aspiration mode for the automated on-line pre
      column derivatization was found to efficiently enhance the method sensitivity and
      precision. Histamine in food samples was efficiently extracted with a methanol
      phosphate buffer solution (50:50, v/v) at 60 degrees C for 30 min, and purified
      with Waters Oasis MCX solid-phase extraction (SPE) cartridge. The limit of
      quantification for this method is 0.2 mg/kg, which is very sensitive for
      histamine determination. With the "sandwich" injection program, 3.7% of relative
      standard deviation (RSD) was achieved by five replicative determinations of a
      sample blank spiked with 0.25 mg/kg histamine standard. Histamine in food samples
      such as fumitory skipjack and mackerel was analyzed with relative recoveries over
      95% at spiking level of 150 mg/kg, as well as canned tuna fish and cheese with
      relative recoveries up to 98% at spiking levels of 0.50 and 5.0 mg/kg,
      respectively. The proposed method was validated with a sample from the Food
      Analysis Performance Assessment Scheme (FAPAS) as a standard certified material;
      and the results (140+/-6 mg/kg) agreed well with the assigned value (139 mg/kg).

PMID- 18822417
TI  - Anion-exchange behavior of several alkylsilica reversed-phase columns.
AB  - Some alkylsilica columns carry a positive charge at low pH, as determined by
      anion-exchange with nitrate ion. In the present study, the relative positive
      charge for 14 alkylsilica columns was measured for a mobile-phase pH 3.0. All but
      3 of these columns were found to carry a significant positive charge under these
      conditions. The relative positive charge on these columns was found to correlate
      approximately with two other column characteristics: relative cation-exchange
      behavior as measured by the hydrophobic-subtraction model (values of C-2.8), and
      slow equilibration of the column to changes in the mobile-phase-as evidenced by a
      slow change in the retention of anionic and cationic solutes with time. The
      origin of this positive charge may arise from the bonding process, with
      incorporation of some cationic entity into the stationary phase.

PMID- 18822418
TI  - Structural and thermal characterizations of silica nanoparticles grafted with
      pendant maleimide and epoxide groups.
AB  - Grafting of free maleimide and epoxide pendant groups onto the surface of
      approximately 7-nm silica nanoparticles was investigated. Glycidyloxypropyl
      groups (3-glycidyloxypropyltrimethoxysilane and 3-aminopropyltrimethoxysilane)
      that carried epoxide groups and aminopropyl groups were grafted to the silica
      surface with the help of condensation reactions. Maleimide groups [1,1(')
      (methylenedi-4,1-phenelene) bismaleimide] were introduced to the silica surface
      via nucleophilic addition reaction with the aminopropyl groups pre-grafted onto
      the surface. The grafted silica samples were characterized using CHN, FTIR, DSC,
      TGA-FTIR, and 13C and 29Si CP/MAS NMR spectroscopy. NMR analyses revealed that
      all the functional groups were covalently bonded to the silica surface and most
      of the maleimide and epoxide rings remained intact on surface. DSC analysis
      showed that the epoxide groups were more reactive than the maleimide groups.

PMID- 18822419
TI  - Homogeneous Ni-P/Al(2)O(3) nanocomposite coatings from stable dispersions in
      electroless nickel baths.
AB  - The dispersion stability of aluminum oxide colloidal particles stabilized with
      comb-polyelectrolytes in an electroless nickel (EN) solution was studied under
      plating conditions (80-90 degrees C). The nanodispersions which were stable at
      room temperature for several weeks flocculate rapidly as the temperature
      approached approximately 65 degrees C. Hydrotropes such as propylene glycol and
      urea are found to induce stability under plating conditions. A dependency of the
      critical flocculation temperature (CFT) on additives, comb-polyelectrolyte
      polyether side chain, and particle morphology is found. The codeposition of
      stabilized and nonstabilized nanoparticle dispersions resulted in very different
      particle density and distribution in the composite coatings. Highly homogeneous
      Ni-P/alumina nanocomposite coatings plated from stabilized baths with up to 50
      vol% particle incorporation have been demonstrated.

PMID- 18822420
TI  - Numerical investigation of transporting droplets by spatiotemporally controlling
      substrate wettability.
AB  - Droplet behaviors on substrates with wettability controlled both in space and in
      time are numerically investigated by using the lattice Boltzmann method. Several
      typical droplet responses are found under different designs of substrate
      wettability control. Special attention is drawn to the conditions under which
      rapid transport of droplets can be achieved. It is found that on alternating non
      wetting-wetting units with proper non-wetting confining stripes, this objective
      can be realized when the frequency of wettability switch approximately matches
      that of the droplet to move across one unit. The variation of the "optimal"
      frequency with the size of the confining stripe is sought within certain ranges.
      The various types of droplet movement are analyzed by looking at the three-phase
      lines on the substrate, as well as the droplet shapes under different conditions.
      The results may provide useful implications for droplet manipulation in
      microfluidic devices.

PMID- 18822421
TI  - Computer-assisted nuclear morphometry in the cytological evaluation of canine
      perianal adenocarcinomas.
AB  - Stained cytological specimens from 18 canine perianal adenocarcinomas were
      analyzed by computer-assisted nuclear morphometry in order to evaluate the
      prognostic value of this technique. In each case, the nuclei of at least 100
      neoplastic hepatoid cells were measured and the mean nuclear area (MNA), mean
      nuclear perimeter (MNP), mean nuclear diameter (D mean), maximum nuclear diameter
      (D max) and minimum nuclear diameter (D min) were calculated. There were
      significant differences in all of these parameters when non-metastatic tumours
      were compared with tumours in which lymph node metastasis had been identified. A
      statistically significant correlation was found between the survival period of
      the dogs and MNA, MNP, D max and D mean. The age of the dog, diameter of the
      tumour and presence of nodal metastasis were also correlated with survival, but
      there was no correlation with breed, sex or D min. These results indicate that
      MNA, MNP, D max and D min may be used as prognostic indicators for canine
      perianal adenocarcinoma.

PMID- 18822422
TI  - Features of an exceptionally narrow QRS data set.
AB  - BACKGROUND: Little attention has been directed to the characteristics of
      electrocardiograms (ECGs) with brief QRS durations (BD). METHODS: From a database
      of 859,977 computer-analyzed (Marquette 12SL, GE Healthcare, Milwaukee, WI, USA)
      ECGs of 216,148 patients, 1805 patients (data set of BD: 19,718 ECGs; age, >18
      years, unpaced), had, in at least one ECG, a QRS duration of less than 62
      milliseconds, a prevalence of 0.8%. RESULTS: The QRS duration ranged from 46 to
      188 milliseconds; values fluctuated between excessive brevity and the
      traditionally normal (80-95 milliseconds), with many values in the 60's. The
      average age at first acquisition was 56 years (range, 18-96 years); 1371 were
      female (76%) and 433 were males (24%); and 416 were white (23%), 1243 African
      American (69%), 109 other (6%). The summed 12-lead QRS amplitude (SigmaQRS)
      ranged from 2800 to 32,929 microV (mean +/- SD, 11,154 +/- 4101), and heart rate
      ranged from 40 to 269 (98 +/- 26). There was a statistically positive
      relationship between QRS duration (in the range 52-105 milliseconds) and SigmaQRS
      (P < 0001): for each 1000 microV increment, duration increased by 0.7
      milliseconds (95% confidence interval [CI], 0.66-0.73 milliseconds). Conversely,
      for each 5-millisecond increment in duration, SigmaQRS increased by 475 microV
      (95% CI, 450-498 microV). There was an inverse relationship between QRS duration
      and heart rate (P < .0001): for every 10 beat rate increase, the duration dropped
      by 1.14 milliseconds (95% CI, 1.09-1.19 milliseconds). An additional data set of
      normal QRS durations ND consisted of 2902 subjects, none of whose 40,327 ECGs
      showed a QRS duration less than 62 milliseconds; 2.8% of ND ECGs had durations in
      the 62-69 millisecond range, 26% in BD. Sinus tachycardia was 43% in BD and 24%
      in ND. The average age of ND was 58 years (range, 18-100 years); 44% were male
      and 56% female; and 39% were white and 57% were African American. A positive
      relationship between duration and amplitude was found among ND subjects as well:
      for each 1000 point increase in SigmaQRS, duration increased by 0.45 milliseconds
      (P < .0001; 95% CI, 0.42-0.47 milliseconds). The duration amplitude relationship
      did not hold for durations greater than 105 milliseconds in either data set.
      CONCLUSION: Over the full extended span of QRS durations (46-106 milliseconds),
      the value of the latter is directly related to the total summed amplitude of the
      12-lead QRS. An inverse relationship is demonstrable with heart rate.

PMID- 18822423
TI  - The relationship between mitral papillary muscles positions and characteristics
      of the QRS complex.
AB  - BACKGROUND: QRS complex characteristics are considered to be one of the most
      significant diagnostic and prognostic determinants for assessment of several
      cardiac conditions. However, there is a large variability of the QRS complex even
      among "normal" individuals. This study was based on 2 assumptions: (1) that the
      portion of the left ventricular endocardium activated earliest is directly
      supplied by the "fanlike" distribution of the anterior, middle, and posterior
      fascicles of the left bundle branch, and (2) that the anterior and posterior
      fascicles course toward their respective mitral papillary muscles. These
      structures could therefore serve as anatomical landmarks to indicate the borders
      of this fanlike distribution of primary "start points" of left ventricular
      activation. AIMS: The primary aim of this study is to test the hypothesis that
      location of both papillary muscles closer to the septum correlates with longer
      QRS duration. The secondary aim of the study is to test the hypothesis that the
      balance of the distances of the anterior and posterior papillary muscles from the
      septum is related to the direction of the frontal plane QRS axis. METHODS: The
      study population consisted of 16 healthy adult volunteers with a mean age of 26
      +/- 9 years, mean height of 170 +/- 12 cm, and mean weight of 68 +/- 10 kg.
      Measurements were done on the magnetic resonance images from all study subjects.
      Positions of papillary muscles were assessed as a predictive variable of QRS
      duration. RESULTS: A significant correlation was found between the closer
      position of both papillary muscles to the septum and longer QRS duration (R =
      0.7, P = .02). Subjects with higher ratio of anterior papillary muscle vs
      posterior papillary muscle free wall angle correlates with inferior rotation of
      the average axis of QRS complex in the frontal plane (R = 0.5, P = .04).
      CONCLUSIONS: The positions of the papillary muscles in relation to the free wall
      and septum wall can be predictive of both QRS duration and the direction of the
      QRS complex of the heart. These results might provide a new basis for prediction
      of QRS complex characteristics of an individual and, thus, differentiate between
      real QRS complex abnormalities and variants of normal.

PMID- 18822424
TI  - The appearance of negative U waves in the precordial leads during balloon
      occlusion of the long posterior descending artery.
AB  - This report presents a patient in which balloon occlusion of the posterior
      descending artery wrapping the apex produced negative U waves in leads V(4-5).
      This case report demonstrates, for the first time, that negative U waves in the
      precordial leads can appear by occlusion of the long posterior descending artery.

PMID- 18822425
TI  - T(peak)T(end) interval in long QT syndrome.
AB  - BACKGROUND: The T(peak)T(end) (T(p)T(e)) interval is believed to reflect the
      transmural dispersion of repolarization. Accordingly, it should be a risk factor
      in long QT syndrome (LQTS). The aim of the study was to determine the effect of
      genotype on T(p)T(e) interval and test whether it was related to the occurrence
      of syncope. METHODS: Electrocardiograms were taken in 95 patients with LQTS drawn
      from the Danish long QT registry (44 patients with KvLQT1, 43 with HERG, and 8
      with SCN5A mutations) and manually evaluated for the QT, QT(peak), and RR
      interval. RESULTS AND CONCLUSION: (1) T(p)T(e) cannot be used to distinguish
      symptomatic from asymptomatic patients with LQTS; (2) HERG patients have longer
      T(p)T(e) than KvLQT1 patients; and (3) there is no need to heart rate-correct
      T(p)T(e) intervals in patients with LQTS.

PMID- 18822426
TI  - Association between foot growth and musculoskeletal loading in children with
      Prader-Willi syndrome before and during growth hormone treatment.
AB  - OBJECTIVE: To explore how foot growth relates to musculoskeletal loading in
      children with Prader-Willi syndrome (PWS). STUDY DESIGN: In 37 children with PWS,
      foot length (FL) before and after 6 years of growth hormone therapy (GHT) was
      retrospectively evaluated with parental and sibling's FL, height, and factors
      reflecting musculoskeletal loading, such as weight for height (WfH), lean body
      mass (LBM; dual energy X-ray absorptiometry, deuterium labeled water), physical
      activity (accellerometry), and walk age. Because of the typically biphasic
      evolution of body mass and the late walk age in PWS, 2 age groups were separated
      (group 1, >2.5 years; group 2, < or =2.5 years). RESULTS: Children with PWS
      normalized height, but not FL after 6 years of GHT. Parental FL correlation with
      PWS's FL was lower than with sibling's FL. In group 1, FL positively correlated
      with WfH, LBM, and physical activity. In group 2, FL negatively correlated with
      age at onset of independent ambulation. Foot catch-up growth with GHT was slower
      in group 2 compared with group 1. CONCLUSION: In PWS, FL is positively associated
      with musculoskeletal loading. Small feet in children with PWS before and during
      long-term GHT may be more than just another dysmorphic feature, but may possibly
      reflect decreased musculoskeletal loading influencing foot growth and genetic and
      endocrine factors.

PMID- 18822428
TI  - Randomized trial of milrinone versus placebo for prevention of low systemic blood
      flow in very preterm infants.
AB  - OBJECTIVE: To assess the effectiveness of early prophylactic milrinone versus
      placebo for prevention of low systemic blood flow in high-risk preterm infants.
      STUDY DESIGN: Double-blind randomized placebo controlled trial of milrinone
      (loading dose 0.75 microg/kg/min for 3 hours then maintenance 0.2 microg/kg/min
      until 18 hours after birth) versus placebo. Infants born <30 weeks gestational
      age and <6 hours of age were eligible and were monitored with serial
      echocardiography, head ultrasound scanning, and continuous invasive blood
      pressure. Primary outcome was maintenance of superior vena cava (SVC) flow > or
      =45 mL/kg/min through the first 24 hours. The exit criterion was hypotension
      unresponsive to volume and inotropes. RESULTS: Ninety infants were enrolled,
      equal proportions maintained SVC flow > or =45 mL/kg/min after treatment
      commenced. No significant difference was observed in SVC flow, right ventricular
      output, and blood pressure during the first 24 hours; or grades 3 to 4
      periventricular/intraventricular hemorrhage and death. Heart rate was higher and
      constriction of the ductus was slower in the infants randomized to milrinone.
      CONCLUSIONS: Milrinone did not prevent low systemic blood flow during the first
      24 hours in very preterm infants, and no adverse effects were attributable to
      milrinone. Use of a preventative treatment with rescue model allowed comparison
      of an inotrope with placebo in this high-risk group of infants.

PMID- 18822427
TI  - Impact of Pseudomonas and Staphylococcus infection on inflammation and clinical
      status in young children with cystic fibrosis.
AB  - OBJECTIVE: To assess the effects of Pseudomonas aeruginosa and Staphylococcus
      aureus infection on lower airway inflammation and clinical status in young
      children with cystic fibrosis (CF). STUDY DESIGN: We studied 111 children age < 6
      years who had 2 P aeruginosa-positive oropharyngeal cultures within 12 months. We
      examined bronchoalveolar lavage fluid (BALF) inflammatory markers (ie, cell
      count, differential, interleukin [IL]-8, IL-6, neutrophil elastase), CF-related
      bacterial pathogens, exotoxin A serology, and clinical indicators of disease
      severity. RESULTS: Young children with CF with both upper and lower airway P
      aeruginosa infection had higher neutrophil counts, higher IL-8 and free
      neutrophil elastase levels, increased likelihood of positive exotoxin A titers,
      and lower Shwachman scores compared with those with positive upper airway
      cultures only. S aureus was associated with increased lower airway inflammation,
      and the presence of both P aeruginosa and S aureus had an additive effect on
      concentrations of lower airway inflammatory markers. BALF markers of inflammation
      were increased with the number of different bacterial pathogens detected.
      CONCLUSIONS: Young children with CF who have upper and lower airway P aeruginosa
      infection have increased endobronchial inflammation and poorer clinical status
      compared with those with only upper airway P aeruginosa infection. The
      independent and additive effects of S aureus on inflammation support the
      significance of polymicrobial infection in early CF lung disease.

PMID- 18822429
TI  - Prospective human leukocyte antigen, endomysium immunoglobulin A antibodies, and
      transglutaminase antibodies testing for celiac disease in children with Down
      syndrome.
AB  - OBJECTIVE: To assess the effect of a prospective screening strategy for the early
      diagnosis of celiac disease (CD) in children with Down syndrome (DS). STUDY
      DESIGN: Blood samples were taken from 155 children with DS. Buccal swabs were
      also taken from 9 of these children for determination of human leukocyte antigen
      (HLA)-DQ2 or HLA-DQ8 positivity. Independently, immunoglobulin A anti-endomysium
      (EMA) and anti-tissue transglutaminase antibodies (TGA) were tested. An
      intestinal biopsy was performed to confirm the diagnosis of CD. RESULTS: Sixty
      three children (40.6%) had test results that were positive for HLA-DQ2 or HLA
      DQ8. Results of HLA DQ-typing of DNA isolated from blood and buccal swabs were
      identical. Eight of the children in whom test results were positive for HLA-DQ2/8
      also had positive test results for EMA and TGA. CD was confirmed in 7 of these
      children with an intestinal biopsy, and in 1 child, CD was suggested with
      improvement on a gluten-free diet. CONCLUSIONS: We found a prevalence of CD in
      children with DS of 5.2% (10 times higher than the general Dutch population). We
      recommend HLA-DQ2/8 typing from buccal swabs in the first year of life and
      initiating serologic screening of children with DS in whom test results are
      positive for HLA-DQ2 or DQ8 at age 3 years. Early knowledge of negative HLA-DQ2/8
      status can reassure most parents that their children do not have a CD risk.

PMID- 18822430
TI  - Health utilization and cost impact of childhood constipation in the United
      States.
AB  - OBJECTIVE: To estimate the total health care utilization and costs for children
      with constipation in the United States. STUDY DESIGN: We analyzed data from 2
      consecutive years (2003 and 2004) of the Medical Expenditure Panel Survey (MEPS),
      a nationally representative household survey. We identified children who either
      had been reported as constipated by their parents or had received a prescription
      for laxatives in a given year. Outcome measures were service utilization and
      expenditures. RESULTS: The MEPS database included a total of 21 778 children age
      0 to 18 years, representing 158 million children nationally. An estimated 1.7
      million US children (1.1%) reported constipation in the 2-year period. No
      differences with respect to age, sex, race, and socioeconomic status were found
      between the children with constipation and those without constipation. The
      children with constipation used more health services than children without
      constipation, resulting in significantly higher costs: $3430/year vs $1099/year.
      This amounts to an additional cost for children with constipation of $3.9
      billion/year. CONCLUSIONS: This study demonstrates that childhood constipation
      has a significant impact on the use and cost of medical care services. The
      estimated cost per year is 3 times than that in children without constipation,
      which likely is an underestimate of the actual burden of childhood constipation.

PMID- 18822431
TI  - Prediction of child abuse risk from emergency department use.
AB  - OBJECTIVE: To examine whether pre-abuse rates and patterns of emergency
      department (ED) visits between children with supported child abuse and age
      matched control subjects are useful markers for abuse risk. STUDY DESIGN: A
      population-based case-control study using probabilistic linkage of four statewide
      data sets. Cases were abused children <13 years of age, identified between
      January 1, 2002, and December 31, 2002. For each case, a birth date-matched,
      population-based control was obtained. Outcome measures were rate ratios of ED
      visits in cases compared with control subjects. RESULTS: Cases (n = 9795) and
      control subjects (n = 9795) met inclusion criteria; 4574 cases (47%) had an ED
      visit; thus linked to the ED database versus 2647 control subjects (27%). The
      crude ED visit rate per 10,000 person-days of exposure was 8.2 visits for cases
      compared with 3.9 visits for control subjects. Cases were almost twice as likely
      as control subjects (adjusted rate ratio = 1.8; 95% CI, 1.5, 1.8) to have had a
      prior ED visit. Leading ED discharge diagnoses were similar for both groups.
      CONCLUSIONS: Children with supported child abuse have higher ED use before abuse
      diagnosis, when compared with the general pediatric population. However, neither
      the rate of ED use nor the pattern of diagnoses offers sufficient specificity to
      be useful markers of risk for abuse.

PMID- 18822432
TI  - Cryptogenic stroke and patent foramen ovale: clinical clues to paradoxical
      embolism.
AB  - BACKGROUND: Patent foramen ovale (PFO) is an independent risk factor for cerebral
      infarction. Since ~25% of the population have a PFO, the simple association of
      PFO with stroke is not enough to establish the diagnosis of paradoxical embolism.
      We evaluated possible clinical clues to the diagnosis of paradoxical embolism.
      METHODS: Among patients with cryptogenic ischemic stroke (CS) who were
      investigated for a right-to-left shunt (RLS), we compared clinical, coagulation
      and biochemical parameters in patients with PFO versus without PFO. RESULTS:
      Among 1689 new patients referred for TIA/non-disabling stroke between 2001 and
      2007, 175 with cryptogenic stroke (CS) were investigated for RLS by transcranial
      Doppler (TCD) bubble studies; 89 (5.5%) with positive TCD had a PFO confirmed by
      TEE. In multivariate logistic regression, a history of DVT or pulmonary embolism
      (OR, 4.39; 95% CI, 1.23-15.69; p=0.023), prolonged travel (OR, 8.77; 95% CI,
      1.775-43.3; p=0.008) , migraine (OR, 2.30: 95% CI, 1.07-4.92; p=0.031), a
      Valsalva maneuver preceding the onset of focal neurological symptoms (OR, 3.33;
      95% CI, 1.15-9.64; p=0.026) and waking up with stroke/TIA (OR, 4.53, 95% CI, 1.26
      16.2; p=0.018) were independently associated with PFO-associated cerebrovascular
      events. Patients with PFO had higher plasma total homocysteine levels than
      patients without PFO (8.9+/-3 versus 7.9+/-2.6 micromol/L respectively; p=0.021).
      CONCLUSIONS: A history of DVT or pulmonary embolism, migraine, recent prolonged
      travel, sleep apnea, waking up with TIA or stroke or a Valsalva maneuver
      preceding the event are clinical clues to the diagnosis of paradoxical embolism
      among patients with CS.

PMID- 18822433
TI  - New treatment measurements for treatment effects on relapses and progression.
AB  - Multiple sclerosis (MS) is considered to be a two stage disease: a first stage in
      which inflammatory phenomena are crucial and a later one in which degenerative
      processes become the hallmark. The role of magnetic resonance imaging (MRI) is
      nowadays of great help both to establish the diagnosis and to rule out other
      conditions. At the clinically isolated syndrome (CIS) stage, MRI is an important
      tool both to predict the appearance of a second attack or the development of
      disability at long term. In the relapsing-remitting (RR) phase of the disease
      conventional MRI is probably less helpful to predict future relapses and
      disability. Cross sectional and longitudinal studies have shown very weak
      correlations between lesion burden on brain T2 and disability in the progressive
      forms of MS. Regarding T2 burden of disease, a plateau effect for EDSS values
      greater than 4.5 has been observed. Measures related to brain or spinal cord
      atrophy together with MR Spectroscopy, Magnetization Transfer Imaging and
      Diffusion Tensor Imaging may be useful in the future to better monitor disease
      progression in the late degenerative phase of the condition. MRI has also been of
      great help in monitoring the effect of immunomodulatory drugs in CIS or RRMS
      clinical trials. Its role to predict treatment response is still controversial on
      an individual basis.

PMID- 18822434
TI  - The implications of immunogenicity for protein-based multiple sclerosis
      therapies.
AB  - Administered proteins are inherently immunogenic, which may influence their
      efficacy or safety when used therapeutically. A review of the published
      literature was performed to compare and evaluate the development and consequences
      of antibodies against therapeutic protein agents for the treatment of multiple
      sclerosis (MS). Interferon beta (IFNbeta), glatiramer acetate (GA), and
      natalizumab are all protein-based therapeutic agents approved to treat MS and are
      associated with the development of antibodies. Both binding antibodies and
      neutralizing antibodies (NAbs) develop to varying degrees in patients treated
      with any of the formulations of IFNbeta. Comparison between studies is
      complicated by differences in methods, assays, criteria for determining NAb
      positivity, treatment duration, and fluctuation of NAb status. Despite these
      confounding factors, current data indicate that high-titer persistent NAbs may be
      relevant in terms of their effect on IFNbeta bioavailability and bioefficacy. GA
      reactive antibodies developed in a high proportion of GA-treated patients, but
      the clinical relevance of these antibodies remains to be established.
      Immunogenicity against natalizumab was associated with reduced efficacy and
      increased incidence of infusion reactions. Other emerging monoclonal antibody
      therapeutics have also been associated with the development of antibodies.
      Experience with generic biosimilars of other protein therapeutics suggests that
      the immunogenicity of generic biosimilar agents cannot be assumed and must be
      established for each formulation.

PMID- 18822435
TI  - Longitudinal changes in myelin water fraction in two MS patients with active
      disease.
AB  - Multiple sclerosis (MS) is characterised by focal areas that undergo cycles of
      demyelination and remyelination. Although conventional magnetic resonance imaging
      is very effective in localising areas of damage, these techniques are not
      pathology specific. A newer technique, T(2) relaxation, can separate water from
      brain into three compartments: (1) a long T(2) component (>2 s) arising from CSF,
      (2) an intermediate T(2) component (~80 ms) attributed to intra- and extra
      cellular water and (3) a short T(2) component (~20 ms) assigned to water trapped
      in between the myelin bilayers (termed myelin water). Histological evidence shows
      that myelin water is a specific marker of myelination. The goal of this work was
      to follow changes in total water content (WC) and myelin water fraction (MWF) in
      evolving MS lesions over one year. Multi-echo T(2) relaxation data was collected
      and used to measure water content and myelin water fraction from three new MS
      lesions in two patients. WC increased in the three large (>1 cm(3)) lesions at
      lesion appearance and remained elevated in the central core. Two lesions showed
      low MWF in the core suggesting demyelination upon first appearance. At later time
      points, one lesion showed a decrease in volume of low MWF, reflecting
      remyelination whereas the volume of low MWF in the other lesion core remained
      constant. This work provides evidence that MWF and WC can monitor demyelination
      and remyelination in MS.

PMID- 18822436
TI  - [Giant cerebellar tuberculoma mimicking a malignant tumor].
AB  - BACKGROUND: Isolated central nervous system (CNS) tuberculoma is rare. Central
      nervous system tuberculosis (TB) is associated with high morbidity and mortality
      despite modern methods of detection and treatment. The authors report a case of a
      giant cerebellar tuberculoma mimicking a malignant tumor and review the
      literature. OBSERVATION: A six-year-old girl, with no past medical history,
      vaccinated for her age, presented with a three-month history of occipitocervical
      cephalalgia, complicated by gait disturbances. The MRI showed a left cerebellar
      tumor suggestive of a medulloblastoma. At surgery, a nodular, avascular lesion
      was found and pathological examination confirmed tuberculoma. Intracranial
      tuberculoma is an uncommon variety of central nervous system tuberculosis. The
      prognosis is related to the rapidity of diagnosis, surgical resection and the
      complementary antituberculosis treatment. CONCLUSION: Intracranial tuberculoma is
      an uncommon variety of central nervous system infection. Prognosis is improved by
      a quick diagnosis, surgical removal, and associated antituberculoma therapy.

PMID- 18822437
TI  - [Cognitive disorders and adult grade II and III gliomas: analysis of a series of
      15 patients].
AB  - BACKGROUND AND PURPOSE: Correlated with better follow-up of gliomas, cognitive
      disorders are increasingly studied. The aim of this study was to describe the
      cognitive disorders presented by these patients at baseline, before any
      treatment, and to evaluate the relations between cognitive disorders and return
      to work. METHODS: A detailed neuropsychological evaluation was administrated to
      15 newly diagnosed patients with a grade II or III glial tumor before any
      treatment. Patients also completed the quality of life and depression scales.
      RESULTS: All patients in our study presented with at least one failed cognitive
      domain during the detailed examination, while the scores on the MMSE scale were
      within the norm. The most deteriorated functions were divided attention and
      episodic verbal and nonverbal memory. Moreover, a significant link was found
      between the number of failed cognitive functions and quality of life. CONCLUSION:
      Cognitive disorders are frequent with glial tumors and impact patients' quality
      of life. Simple tests of global cognitive status are not sufficient to detect
      cognitive difficulties in these patients. Consequently, detailed and adapted
      neuropsychological assessment is necessary, especially to detect deteriorated
      problems with memory, divided attention, or processing speed in this population.

PMID- 18822438
TI  - Steroidal glycosides from the underground parts of Trillium erectum and their
      cytotoxic activity.
AB  - Six steroidal glycosides, along with 14 known compounds, were isolated from the
      underground parts of Trillium erectum L. (Liliaceae). The structures of 1-6 were
      determined on the basis of extensive spectroscopic analysis, including two
      dimensional (2D) NMR data, and a few chemical transformations. The isolated
      compounds were evaluated for their cytotoxic activity against HL-60 human
      promyelocytic leukemia cells.

PMID- 18822439
TI  - Toxoplasma gondii infection in pregnant women in China.
AB  - Infection with Toxoplasma gondii is common and usually asymptomatic, but it can
      have serious consequences in pregnant women if passed to the developing fetus.
      The aims of this study were to determine the prevalence of toxoplasmosis in
      pregnant women and to identify the possible risk factors associated with T.
      gondii infection in China. Of a sample of 235 pregnant women in Changchun, China,
      25 (10.6%) were found by ELISA to be positive for IgG and none (0%) for IgM.
      Major risk factors were found by bivariate and multivariate analysis to include
      eating raw or undercooked meat, unwashed raw vegetables or fruit, contact with
      cats, living in rural areas, and low educational standards. In order to lower
      congenital infection, pregnant women need to be informed about the risk factors
      for toxoplasmosis.

PMID- 18822440
TI  - Neutralizing activity of antibodies to the V3 loop region of HIV-1 gp120 relative
      to their epitope fine specificity.
AB  - The V3 loop of HIV-1 gp120 is considered occluded on many primary viruses.
      However, virus sensitivity to neutralization by different V3 mAbs often varies,
      indicating that access to V3 is not restricted equally for all antibodies. Here,
      we have sought to gain a better understanding of these restrictions by
      determining the neutralizing activities of 7 V3 mAbs (19b, 39F, CO11, F2A3, F530,
      LA21, and LE311) against 15 subtype B primary isolates and relating these
      activities to the fine specificity of the mAbs. Not surprisingly, we found that
      most mAbs neutralized the same 2-3 viruses, with only mAb F530 able to neutralize
      2 additional viruses not neutralized by the other mAbs. Epitope mapping revealed
      that positively-charged residues in or near the V3 stem are important for the
      binding of all the mAbs and that most mAbs seem to require the Pro residue that
      forms the GPGR beta hairpin turn in the V3 tip for binding. Based on the mapping,
      we determined that V3 sequence variation accounted for neutralization resistance
      of approximately half the viruses tested. Comparison of these results to those of
      select V3 mAbs with overall better neutralizing activities in the light of
      structural information illustrates how an antibody's mode of interaction with V3,
      driven by contact residue requirements, may restrict the antibody from accessing
      its epitope on different viruses. Based on the data we propose an angle of
      interaction with V3 that is less stringent on access for antibodies with cross
      neutralizing activity compared to antibodies that neutralize relatively fewer
      viruses.

PMID- 18822441
TI  - Toward understanding the mechanism of improving the production of volatile fatty
      acids from activated sludge at pH 10.0.
AB  - A well-defined fractionation approach for sludge flocs was applied to a better
      understanding of the underlying mechanism of improving the production of volatile
      fatty acids (VFA) in the hydrolysis and acidification processes at pH 10.0.
      Specifically, sludge flocs were fractionated through centrifugation and
      ultrasound into four fractions: (1) slime, (2) loosely bound extracellular
      polymeric substances (LB-EPS), (3) tightly bound EPS (TB-EPS) and (4) pellet.
      Result showed that during 20 days of fermentation, the total VFA production at pH
      10.0 was higher, from 2 to 34 times, than that at pH 5.5. At pH 10.0, however,
      the enzyme activities (i.e. protease, alpha-amylase, alkaline phosphatase and
      acid phosphatase) in all fractions of sludge flocs were all lower than pH 5.5,
      which strongly suggests that the biotic effect was not the leading cause of the
      VFA improvement. Further investigation suggests that pH 10.0 could significantly
      improve the VFA production through the break of sludge matrix which is usually
      hydrolyzed by the extracellular enzymes embedded in itself, increase the
      effective contact between extracellular organic matters and enzymes, and create a
      favorable environment for microbes to accumulate VFA. Hydrolysis and
      acidification at pH 10.0 can be considered as part of an appropriate solution for
      tertiary treatment and contribute to the headway toward the goal of sustainable
      water treatment technologies.

PMID- 18822442
TI  - Effect of nitrate on the performance of single chamber air cathode microbial fuel
      cells.
AB  - The effect of nitrate on the performance of a single chamber air cathode MFC
      system and the denitrification activity in the system were investigated. The
      maximum voltage output was not affected by 8.0mM nitrate in the medium solution
      at higher external resistance (270-1000Omega), but affected at lower resistance
      (150Omega) possibly due to the low organic carbon availability. The Coulombic
      efficiency was greatly affected by the nitrate concentration possibly due to the
      competition between the electricity generation and denitrification processes.
      Over 84-90% of nitrate (0.8-8.0mM) was removed from the single chamber MFCs in
      less than 8h in the first batch. After 4-month operation, over 85% of nitrate
      (8.0mM) was removed in 1h after the MFC was continuously fed with a medium
      solution containing nitrate. Only a small amount of nitrite (<0.01mM) was
      detected during the denitrification process. The similar denitrification activity
      observed at different external resistances (1000 and 270Omega) and open circuit
      mode indicates that the denitrification was not significantly affected by the
      electricity generation process. No electricity was generated when the MFC fed
      with 8.0mM nitrate was moved to a glove box (no oxygen), indicating that the
      bacteria on the cathode did not involve in accepting electrons from the circuit
      to reduce the nitrate. Denaturing Gradient Gel Electrophoresis (DGGE) profiles
      demonstrate a similar bacterial community composition on the electrodes and in
      the solution but with different dominant species.

PMID- 18822443
TI  - Polychlorinated dibenzo-p-dioxins and dibenzofurans in soils and sediments from
      Daliao River Basin, China.
AB  - Polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/F) were
      analyzed in surface sediments and top soils collected from 30 sites in Daliao
      River Basin. The concentrations of PCDD/F ranged from 0.28 to 29.01 ng TEQ kg(-1)
      dw (mean value, 7.45 ng TEQ kg(-1)dw) in sediments, and from 0.31 to 53.05 ng TEQ
      kg(-1)dw (mean value, 7.00 ng TEQ kg(-1)dw) in soils. PCDD/F pollution in
      sediments from the mid- and downstream sections of Hun River was found to be
      relatively heavy, and the levels of PCDD/F contamination in paddy soils were
      generally higher than those of upland soils. Using multivariate statistical
      analysis, the PCDD/F homologue and congener profiles of all soil and sediment
      samples were compared with those of suspected PCDD/F sources. The results showed
      that, PCDD/F contamination in most sediments of Hun River should mainly
      originated from the production of organochlorine chemicals, while metal smelting
      was the important potential source of PCDD/F in the drainage area of Taizi River.
      PCDD/F contamination in paddy soils should be simultaneously attributed to the
      polluted water irrigation and the organochlorine pesticide application.

PMID- 18822444
TI  - Do uncertainty analyses reveal uncertainties? Using the introduction of DNA
      vaccines to aquaculture as a case.
AB  - The Walker and Harremoes (W&H) uncertainty framework is a tool to systematically
      identify scientific uncertainty. We applied the W&H uncertainty framework to
      elicit scientists' judgements of potential sources of uncertainty associated with
      the use of DNA vaccination in aquaculture. DNA vaccination is considered a
      promising solution to combat pathological fish diseases. There is, however, lack
      of knowledge regarding its ecological and social implications. Our findings
      indicate that scientists are open and aware of a number of uncertainties
      associated with DNA vaccination e.g. with regard to immune response, degradation
      and distribution of the DNA plasmid after injection and environmental release,
      and consider most of these uncertainties to be adequately reduced through more
      research. We proceed to discuss our experience of using the W&H uncertainty
      framework. Some challenges related to the application of the framework were
      recognised. This was especially related to the respondents' unfamiliarity with
      the concepts used and their lack of experience in discussing qualitative aspects
      of uncertainties. As we see it, the W&H framework should be considered as a
      useful tool to stimulate reflection on uncertainty and an important first step in
      a more extensive process of including and properly dealing with uncertainties in
      science and policymaking.

PMID- 18822445
TI  - Effects of reduced nitrogen compounds on epiphytic lichen communities in
      Mediterranean Italy.
AB  - The effects of reduced nitrogen compounds on epiphytic lichen vegetation have
      been largely investigated in northern Europe. This paper reports for the first
      time results of a study carried out on pine trees in the Mediterranean basin.
      Contrary to the usual acidophytic lichen colonization of pine bark, in this case
      a nitrophytic lichen vegetation was found, suggesting that the study area is
      characterized by a diffuse eutrophication. Tree circumference, distance from the
      stock farms, bark pH and bark electrical conductivity emerged as the main factors
      influencing the distribution and abundance of epiphytic lichens in the study
      area. Both Hyperphyscia adglutinata and Xanthoria parietina were suitable local
      indicator species of high pine bark pH values. However, while X. parietina
      indicated high nitrogen dust pollution, H. adglutinata occurred also where there
      was an additional increase in bark pH caused by the release of high amounts of
      ammonia. The increased nitrogen availability caused by ammonium apparently had no
      effect on the occurrence of nitrophytes.

PMID- 18822446
TI  - Removal of organics in constructed wetlands with horizontal sub-surface flow: a
      review of the field experience.
AB  - Constructed wetlands with horizontal sub-surface flow (HF CWs) have successfully
      been used for treatment various types of wastewater for more than four decades.
      Most systems have been designed to treat municipal sewage but the use for
      wastewaters from agriculture, industry and landfill leachate in HF CWs is getting
      more attention nowadays. The paper summarizes the results from more than 400 HF
      CWs from 36 countries around the world. The survey revealed that the highest
      removal efficiencies for BOD(5) and COD were achieved in systems treating
      municipal wastewater while the lowest efficiency was recorded for landfill
      leachate. The survey also revealed that HF CWs are successfully used for both
      secondary and tertiary treatment. The highest average inflow concentrations of
      BOD(5) (652 mg l(-1)) and COD (1865 mg l(-1)) were recorded for industrial
      wastewaters followed by wastewaters from agriculture for BOD(5) (464 mg l(-1))
      and landfill leachate for COD (933 mg l(-1)). Hydraulic loading data reveal that
      the highest loaded systems are those treating wastewaters from agriculture and
      tertiary municipal wastewaters (average hydraulic loading rate 24.3 cm d(-1)). On
      the other hand, landfill leachate systems in the survey were loaded with average
      only 2.7 cm d(-1). For both BOD(5) and COD, the highest average loadings were
      recorded for agricultural wastewaters (541 and 1239 kg ha(-1) d(-1),
      respectively) followed by industrial wastewaters (365 and 1212 kg ha(-1) d(-1),
      respectively). The regression equations for BOD(5) and COD inflow/outflow
      concentrations yielded very loose relationships. Much stronger relationships were
      found for inflow/outflow loadings and especially for COD. The influence of
      vegetation on removal of organics in HF CWs is not unanimously agreed but most
      studies indicated the positive effect of macrophytes.

PMID- 18822447
TI  - Source apportionment of human personal exposure to volatile organic compounds in
      homes, offices and outdoors by chemical mass balance and genetic algorithm
      receptor models.
AB  - A number of past studies have shown the prevalence of a considerable amount of
      volatile organic compounds (VOCs) in workplace, home and outdoor
      microenvironments. The quantification of an individual's personal exposure to
      VOCs in each of these microenvironments is an essential task to recognize the
      health risks. In this paper, such a study of source apportionment of the human
      exposure to VOCs in homes, offices, and outdoors has been presented. Air samples,
      analysed for 25 organic compounds and sampled during one week in homes, offices,
      outdoors and close to persons, at seven locations in the city of Leipzig, have
      been utilized to recognize the concentration pattern of VOCs using the chemical
      mass balance (CMB) receptor model. In result, the largest contribution of VOCs to
      the personal exposure is from homes in the range of 42 to 73%, followed by
      outdoors, 18 to 34%, and the offices, 2 to 38% with the corresponding
      concentration ranges of 35 to 80 microg m(- 3), 10 to 45 microg m(- 3) and 1 to
      30 microg m(- 3) respectively. The species such as benzene, dodecane, decane,
      methyl-cyclopentane, triethyltoluene and trichloroethylene dominate outdoors;
      methyl-cyclohexane, triethyltoluene, nonane, octane, tetraethyltoluene, undecane
      are highest in the offices; while, from the terpenoid group like 3-carane,
      limonene, a-pinene, b-pinene and the aromatics toluene and styrene most influence
      the homes. A genetic algorithm (GA) model has also been applied to carry out the
      source apportionment. Its results are comparable with that of CMB.

PMID- 18822448
TI  - Concomitant antiplatelet and anticoagulation therapy: indications, controversies
      and practical advice.
AB  - The use of combination antiplatelet and anticoagulant therapy is commonly
      encountered in clinical practice and is often a source of clinical controversy in
      regards to the efficacy versus the safety of this regimen. The benefit of
      combination therapy relates to the probable additive effect of suppressing both
      platelet and coagulation factor activities. The risk of dual therapy is the
      potential for increased hemorrhagic events which may outweigh the clinical
      benefit. This review will focus on the clinical evidence that has demonstrated
      greater efficacy with combination therapy over either antiplatelet or
      anticoagulant therapy alone. Clinicians should consider the importance of
      documentation of combination therapy use in their patients in an effort to target
      those patients with the greatest benefit, and to avoid unnecessary complications.

PMID- 18822449
TI  - Minimal effect of cold ischemia time on progression to late-stage chronic kidney
      disease observed long term after partial nephrectomy.
AB  - OBJECTIVES: To assess the influence of cold ischemia on postoperative renal
      function and the new onset of late-stage chronic kidney disease during long-term
      follow-up after partial nephrectomy. METHODS: A total of 131 patients with renal
      tumors who underwent partial nephrectomy and were followed up for >or=12 months
      were included in the present study. Renal function was analyzed using the
      estimated glomerular filtration rate (e-GFR). RESULTS: We classified the subjects
      into 3 groups according to the length of cold ischemia time: group 1, 1-30
      minutes; group 2, 31-60 minutes; and group 3, >60 minutes. Although the
      postoperative e-GFR was lower in group 3 than in groups 1 and 2, no significant
      difference was found among the 3 groups during long-term follow-up when
      preoperative CKD was absent. A cold ischemia time of >or=44 minutes significantly
      increased the probability of freedom from the new onset of an e-GFR of <45
      mL/min/1.73 m(2), but this difference was minimal. Multivariate analysis showed
      that the preoperative e-GFR and the relative decrease of e-GFR at 1 year after
      surgery were the significant factors determining postoperative renal function.
      CONCLUSIONS: A cold ischemia time of >44 minutes appears to be a threshold
      influencing the new onset of late-stage CKD; however, it was not a significant
      factor on multivariate analysis. Thus, renal hypothermia appears to prevent the
      deterioration of renal function long term after surgery for patients undergoing a
      longer ischemia time.

PMID- 18822450
TI  - Ovotesticular disorder of sexual development (true hermaphroditism).
AB  - OBJECTIVES: To determine the mechanism for the 46,XX/46,XY karyotype observed in
      a patient with an ovotesticular disorder of sexual development (ie, true
      hermaphroditism). METHODS: Cytogenetic, molecular cytogenetic, and molecular DNA
      analyses were performed on the blood, skin, and left and right gonadal tissue
      from 2 surgical procedures. The results of these studies were used to determine
      whether the ovotesticular disorder of sexual development resulted from mosaicism
      or tetragametic chimerism. RESULTS: Cytogenetic and molecular analyses revealed a
      mixture of 46,XX and 46,XY cells in most tissues. DNA analysis from the gonadal
      tissues from surgeries 1 and 2 was performed. Highly polymorphic loci from 12
      different chromosomes were examined for the presence of > or = 1 paternal or
      maternal alleles. Three loci were highly informative: D14S544 (14q32.2), DS14S583
      (14q21.3), and SE33 (6q14). Each demonstrated the presence of 2 paternal and 2
      maternal alleles, indicating that the ovotesticular disorder of sexual
      development resulted from tetragametic chimerism. CONCLUSIONS: Based on the
      findings of the cytogenetic, molecular cytogenetic, and DNA analyses of the
      polymorphic markers from several different loci, it was confirmed that the
      patient had tetragametic chimerism. This case has assisted in increasing our
      knowledge of the possible mechanisms causing this rare and complex disorder.

PMID- 18822451
TI  - Single center, single operator comparative study of the effectiveness of
      electrohydraulic and electromagnetic lithotripters in the management of 10- to 20
      mm single upper urinary tract calculi.
AB  - OBJECTIVES: This study compared the efficacy and safety profile of
      electrohydraulic (EH) and electromagnetic (EM) lithotriptors in the treatment of
      10- to 20-mm renal and proximal ureteric stones at a single center and by a
      single operator. METHODS: Between January 2001 and December 2006, we sequentially
      treated patients meeting study inclusion criteria with MPL 9000 Dornier EH for
      the first 3 years, followed by the EM Siemens Modularis shockwave lithotripsy
      (SWL) unit. A single operator performed all SWL treatments under the supervision
      of an admitting urologist. We analyzed the demographic features and stone- and
      treatment-related parameters including complications for both groups. In each
      group, the stone-free rate and efficiency quotient was determined at 1-3 months.
      RESULTS: Of 274 patients, we sequentially treated 112 using the EH lithotriptor,
      and 162 the EM lithotriptor. The pre-SWL patients and stone-related parameters
      were similar in the two groups, except for diagnostic imaging modalities. The
      mean number of SWL sessions, need for ancillary procedure, retreatment rate,
      stone location, stone-free rate, and efficiency quotient were not significantly
      different between groups. The mean number of shockwaves required for complete
      fragmentation was 2977 and 6044 (P < .000) for the EH and EM groups,
      respectively. CONCLUSIONS: Single center, single operator experience with two
      types of lithotriptor indicated that both are equally efficacious, with similar
      safety profiles. The only significant difference was that the EH lithotriptor
      required fewer shockwaves for fragmentation.

PMID- 18822452
TI  - Some criteria to attempt second side safely in planned bilateral simultaneous
      percutaneous nephrolithotomy.
AB  - OBJECTIVES: To determine the validity of some criteria that could guide in the
      decision to cancel or proceed with the second side of planned bilateral
      simultaneous percutaneous nephrolithotomy (bsPCNL). METHODS: Patients with an
      indication for bilateral PCNL were enrolled in this study. The operation was
      stopped at the end of the initial side if operative time was >180 min, the
      hemoglobin level was <11 g/dL, the hemoglobin decrease was >3 g/dL, the systolic
      arterial pressure was <100 mm Hg, the arterial oxygen saturation was <95%, the
      arterial blood pH was <7.35, or the blood sodium was <128 mg/mL. The success and
      complication rates were compared in patients who underwent second side PCNL
      (group 1) and those for whom the procedure was stopped after the initial side
      (group 2). RESULTS: Of 42 planned bsPCNLs, 12 were stopped after the initial
      side, with the cause being prolonged operative time in 7, hemoglobin decrease in
      6, systolic arterial pressure decrease in 2, arterial oxygen saturation decrease
      in 2, pH decrease in 1, and sodium decrease in 1. Differences in patient
      characteristics, stone burdens, and overall success and complication rates were
      insignificant. Transfusion, postoperative urinary infection, and prolonged urine
      drainage rates were similar, but the total hospitalization time was significantly
      longer in group 2. One hydrothorax and one renal pelvic perforation occurred in
      group 2. The need for transfusion correlated positively with the number of
      nephrostomy tracts in group 2 (r = 0.895, P = .001). No such correlation was
      found in group 1. CONCLUSIONS: Despite the best of intentions, about 30% of
      anticipated bsPCNL cases might be limited to single-sided PCNL, depending on the
      intraoperative events. Our criteria seem reasonable, because similar success and
      complication rates were obtained with bilateral, separate-session PCNL and
      bsPCNL. These criteria can be considered in the decision making to omit the
      advantages of a single session for safety.

PMID- 18822453
TI  - The newer the better? Comparison of the 1997 and 2001 partin tables for
      pathologic stage prediction of prostate cancer in China.
AB  - OBJECTIVES: The use of the Partin tables for pathologic stage prediction of
      prostate cancer in China has 2 problems. First, the validity of such U.S.-derived
      predictive tools has not been tested in China. Second, because an updated version
      of the Partin tables created using a more contemporary cohort was introduced in
      2001, it is important to determine whether this renewed version (2001 Partin
      tables) is superior to the old version (1997 Partin tables). To investigate these
      problems, we compared these 2 predictive tools for their ability to predict the
      pathologic stage in Chinese patients. METHODS: From June 2001 to May 2007, 271
      consecutive patients who met the inclusion criteria for Partin table prediction
      and underwent radical prostatectomy for clinically localized prostate cancer at a
      single center were evaluated. The predictive accuracy of the 1997 Partin tables
      and 2001 Partin tables were assessed using receiver operating characteristics
      analysis. RESULTS: For the 1997 Partin tables, the area under the receiver
      operating characteristics curve for the prediction of organ-confined disease,
      established capsular penetration, seminal vesicle involvement, and lymph node
      involvement was 0.723, 0.674, 0.749, and 0.781, respectively. The corresponding
      values for the 2001 Partin tables were consistently low at 0.604, 0.539, 0.654,
      and 0.631. CONCLUSIONS: The results of our study have confirmed good predictive
      accuracy for the 1997 Partin tables for Chinese patients, but not for their
      updated 2001 version.

PMID- 18822454
TI  - Nevirapine induces growth arrest and premature senescence in human cervical
      carcinoma cells.
AB  - OBJECTIVE: The aim of this study was to assess the impact of nevirapine on a
      cervix carcinoma cell line. METHODS: HeLa cells were cultured in Dulbecco's
      modified Eagle medium supplemented with 20% fetal bovine serum at 37 degrees C
      and humidified 10% CO(2) in air. Nevirapine was purified from commercially
      available Viramune (Boehringer-Ingelheim), diluted in dimethyl sulfoxide (DMSO,
      Sigma-Aldrich) in 350 microMu final concentration and added to cell cultures 5 h
      after seeding. The same DMSO volume (0.2% final concentration) was added to
      controls. RESULTS: We found that nevirapine treatment induces reversible growth
      arrest and produces morphological changes in treated cells. In contrast with
      previous reports the observed effects of nevirapine did not correlate with
      promotion of differentiation, but with induction of premature senescence.
      Premature senescence as a response to anti-tumour treatment is a common effect of
      the most anti-cancer chemotherapeutics. Nevirapine treated cells strongly
      accumulated SA-b-Gal activity and also expressed increased levels of p53 and p21
      when analyzed via RT-PCR. In order to further explore the potent mechanisms of
      premature senescence induction we performed pChk2-Thr68 immunofluorescence
      analysis and found that nevirapine treated cells exhibited increased number of
      nuclear foci, indicating activated DNA damage response. CONCLUSION: We propose
      that at least in HeLa cell line nevirapine treatment exerts an effect far from
      the differentiation process, by introducing the cells into premature senescence.
      Based on these data, the effects of RT inhibitors should be further investigated
      since they may represent an additional agent against human cancer.

PMID- 18822455
TI  - The effects of simulated stuttering and prolonged speech on the neural activation
      patterns of stuttering and nonstuttering adults.
AB  - Functional magnetic resonance imaging was used to investigate the neural
      correlates of passive listening, habitual speech and two modified speech patterns
      (simulated stuttering and prolonged speech) in stuttering and nonstuttering
      adults. Within-group comparisons revealed increased right hemisphere biased
      activation of speech-related regions during the simulated stuttered and prolonged
      speech tasks, relative to the habitual speech task, in the stuttering group. No
      significant activation differences were observed within the nonstuttering
      participants during these speech conditions. Between-group comparisons revealed
      less left superior temporal gyrus activation in stutterers during habitual speech
      and increased right inferior frontal gyrus activation during simulated stuttering
      relative to nonstutterers. Stutterers were also found to have increased
      activation in the left middle and superior temporal gyri and right insula,
      primary motor cortex and supplementary motor cortex during the passive listening
      condition relative to nonstutterers. The results provide further evidence for the
      presence of functional deficiencies underlying auditory processing, motor
      planning and execution in people who stutter, with these differences being
      affected by speech manner.

PMID- 18822456
TI  - Polygenes, risk prediction, and targeted prevention of breast cancer.

PMID- 18822457
TI  - Polygenes, risk prediction, and targeted prevention of breast cancer.

PMID- 18822458
TI  - Graves' disease.

PMID- 18822459
TI  - Graves' disease.

PMID- 18822460
TI  - Graves' disease.

PMID- 18822461
TI  - Overdoing safety wrap.

PMID- 18822462
TI  - Primate gloom.

PMID- 18822463
TI  - Bee fears heighten.

PMID- 18822464
TI  - Pesticides linked to bee deaths.

PMID- 18822465
TI  - Darwin television celebrations begin.

PMID- 18822466
TI  - Clavicle fractures during birth.

PMID- 18822467
TI  - Access to cancer drugs: local autonomy or local tyranny?

PMID- 18822468
TI  - The pathogenesis of gout.
AB  - An elevated serum urate level, together with local factors, can result in the
      deposition of urate crystals into the joints. Once crystals are deposited into a
      joint, they can be released into the joint space and initiate an inflammatory
      cascade causing acute gouty arthritis. These acute flares resolve, but the
      crystals remain in the joint. The way to ultimately correct the underlying
      metabolic problem of hyperuricemia and the crystal deposition is to lower the
      serum urate level and dissolve the crystal deposits. This will stop both the
      acute attacks and the progressive joint damage.

PMID- 18822469
TI  - Clinical manifestations of hyperuricemia and gout.
AB  - Biologically significant hyperuricemia occurs when serum urate levels exceed
      urate solubility, ie, at approximately 6.8 mg/dL. At serum urate levels above
      this threshold, manifestations of chronic crystal deposition, including gouty
      arthritis, may occur, although asymptomatic hyperuricemia often persists for many
      years without progression. Intercritical asymptomatic periods follow the
      resolution of acute gout flares, but crystals remain in the joint during these
      intervals and further deposition may continue silently. Ultimately this may lead
      to persistent attacks, chronic pain, and, in some patients, joint damage.

PMID- 18822470
TI  - The role of hyperuricemia and gout in kidney and cardiovascular disease.
AB  - Elevated serum urate levels are recognized as leading to gouty arthritis, tophi
      formation, and uric acid kidney stones. While serum urate elevations have long
      been associated with renal disease, they are not usually considered to have a
      causal role in kidney dysfunction. However, recent epidemiologic studies have
      identified serum urate elevations as an independent risk factor for chronic
      kidney disease. Hyperuricemia has also been found to be an independent risk
      factor for cardiovascular disease and hypertension. An animal model of mild
      hyperuricemia has shed new light on a potential mechanism of microvascular
      changes leading to endothelial dysfunction, a precursor to both coronary artery
      disease and hypertension. Additional animal studies and recent epidemiologic
      findings have provided further evidence that soluble urate is a risk factor for
      nonarticular disease.

PMID- 18822471
TI  - The gout diagnosis.
AB  - Synovial fluid aspiration and analysis is the gold standard for making the
      diagnosis of gout but is not always performed when indicated in clinical
      practice. In clinical situations when joint aspiration simply cannot be
      performed, a presumptive (or clinical) diagnosis of gout may be made in
      consultation with published recommendations and criteria from expert societies. A
      thorough patient history and physical examination are critical to a presumptive
      diagnosis of gout, as is serum urate measurement at the time of an acute attack
      and at follow-up 2 weeks later.

PMID- 18822472
TI  - [Pulmonary hemorrhages].

PMID- 18822473
TI  - [Inhalational antibacterial therapy for an exacerbation of chronic obstructive
      pulmonary disease].
AB  - The clinical efficiency of inhalational antibacterial therapy for Stage II
      chronic obstructive pulmonary disease (COPD) was evaluated in 100 patients who
      had been randomized to an inhalational fusafungine group (n = 50) and a systemic
      (per os or parenteral) antibiotics group (n = 50). Inhalational antibacterial
      therapy for exacerbations of Stage II COPD was found to be as effective as
      systemic use of antibiotics. Moreover, side effects of inhalational therapy were
      much less pronounced.

PMID- 18822474
TI  - [Tuberculin sensitivity in old children with new-onset active tuberculosis].
AB  - In recent years, there have been reports on the reduced diagnostic value of a
      tuberculin test with 2 TE PPD-L. Tuberculin diagnosis is a ground for suspecting
      tuberculosis only in 25.9 +/- 0.06% of cases in senior pupils and in 10.7 +/-
      0.03% amongst adolescents. This is associated with the higher proportion
      tuberculin-positive individuals and it is very difficult to make the diagnosis in
      children with monotonous tuberculin sensitivity. A contact with a bacterium
      discharging person undoubtedly increases a risk for the disease, but fails to
      affect the true outcome of delayed hypersensitivity. According to the date of
      this study, comorbidity and helminthic invasion have no significant impact on
      tuberculin sensitivity. Reactivation impairs immune homeostasis towards
      inadequate immune system performance.

PMID- 18822475
TI  - [Diagnostic characteristics of adenosine deaminase test in Byelorussian patients
      with tuberculous pleurisy].
AB  - The results of studying the diagnostic value of changes in the pleural fluid and
      serum activities of adenosine deaminase (ADA) and its isozymes are analyzed in
      Byelorussian patients with tuberculous pleurisy. There is an increased serum and
      pleural fluid ADA activity in the patients with tuberculous pleurisy caused
      mainly by a rise in ADA2 activity. The test determining the activity of ADA, and
      ADA2 in particular, has shown high sensitivity and specificity as compared with
      the results obtained in other countries. The diagnostic efficacy of determination
      of these indices in the serum is also high, but it is lower than that in the
      pleural fluid.

PMID- 18822476
TI  - [X-ray endovascular surgery in the trauma and orthopedic unit].
AB  - The review of X-ray endovascular surgical methods applied in the practice of FSF
      CITO named after N.N. Priorov since 1970 is presented. The complex evaluation of
      the altered conditions of performing angiographic examinations for the time
      present was carried out. The main regulations of anesthesiological provisions for
      angiographic studies in conditions of an in-patient trauma department are
      described. The methods of interventional X-ray surgery became use in patients
      with vertebral column and spinal medulla injuries, traumas with the threat of
      pulmonary thromboembolism and in patients with bone pathology. More than 200
      patients with a traumatic disease of the spinal medulla and scoliotic deformities
      were investigated. In all patients spinal angiography with the evaluation of the
      spinal cord blood supply was performed. The results of more than 450 angiographic
      examinations the patients with bone pathology are presented. In 83 cases X-ray
      endovascular embolizations of the regional blood flow were done. 63 Cava Filters
      were implanted in patients with floating pelvic and leg vein thrombosis. Own
      expertise of the use of tentative Cava Filters is described. These and other data
      testify of X-ray endovascular methods prove to be in demand in traumatological
      and orthopedic practice. Their application will open new possibilities for
      traumatologists and orthopedists in the process of preventive measures,
      diagnostics and treatment the patients

PMID- 18822477
TI  - [Surgical treatment of spine deformities in patients with systemic hereditary
      spine diseases].
AB  - Experience in treatment of 55 patients with spine deformities developed on the
      background of systemic hereditary spine diseases is presented. Algorithm of the
      examination and treatment tactics for this group of patients is presented.
      Features of surgical technique in dorsal, ventral and combined approaches are
      described.

PMID- 18822478
TI  - [New facilities in management of complex regional pain upper limb syndrome with
      thoracoscopic sympathectomy].
AB  - 26 patients (21 females and 5 males, aged from 40 to 70 years) with complex
      regional pain syndrome (CRPS) who underwent thoracic sympathectomy at the Th3-4
      level on the damaged side, were examined 1,5-2 months since trauma. After an
      operation all patients showed pain management, improvement of motor and trophic
      functions, positive dynamics of laser Doppler flowmetry and computer
      thermography. The given method was demonstrated to be effective and mostly
      successful at the early stages of CRPS.

PMID- 18822479
TI  - [Spa and resort treatment of patients with ischemic heart disease including
      magnetopeloido therapy and sulfurated hydrogen baths].

PMID- 18822480
TI  - [The use of nitric-silica mineral water in combined rehabilitative therapy of
      musculotonic dorsopathy syndromes].
AB  - Nitric-silica baths had beneficial myoadaptive and analgesic effect on patients
      with reflex dorsopathy syndromes. Balneotherapy combined with the treatment by
      sinusoidal modulated currents, massage, and remedial gymnastics was efficacious
      in alleviating musculotonic and orthopedic problems in patients with lumbar
      osteochondrosis. This effect was more pronounced than with the use of gas-bubble
      baths due to the improvement of trophic processes in the muscular tissue of the
      affected back and limb regions.

PMID- 18822481
TI  - [Combination of modern physiotherapeutic methods in rehabilitation of patients
      with osteoarthrosis and rheumatoid arthritis after arthroscopic surgery on the
      knee joint].
AB  - Duration of the rehabilitation period after arthroscopic surgery on the knee
      joint was reduced by the use of a combination of two modern physiotherapeutic
      modalities, local cryo-aerotherapy and electrostimulation of smooth muscle
      components of vascular walls using a Lymphavision apparatus (5-7 sessions). This
      treatment was given to 55 patients with osteoarthrosis following arthroscopic
      meniscal resection and abrasive chondropasty and to 20 ones with rheumatoid
      arthritis after arthroscopic total synovectomy. All patients reported alleviation
      of pain and oedema in the affected joint. The rehabilitation period was 2-5 days
      shorter than after the traditional treatment.

PMID- 18822482
TI  - [Effect of tiotropium bromide on exercise tolerance in patients with chronic
      obstructive pulmonary disease].
AB  - This open prospective randomized parallel-group comparative study included 43
      patients with moderate or severe chronic obstructive pulmonary disease (COPD).
      The patients of active working age were referred to the disability groups II-III
      based on the average forced expiratory volume in 1 second (1.70+/0.43 1 or 49.1+/
      10.7% the normal value) and received an eight-week course of pulmonary
      rehabilitation. During the study, the patients were given tiotropium bromide (TB)
      for 14 weeks to assess its effect on the tolerance of physical activity. A
      combination of TB with pulmonary rehabilitation was shown to improve tolerance
      evaluated by whole-body rheography (WBR) in a 6 minute step-test and the standard
      functional test. Also, this treatment resulted in the clinically significant
      alleviation of dyspnea and permitted to decrease the intake of salbutamol (used
      "as required") compared with pulmonary rehabilitation alone. It is concluded that
      combination of TB and pulmonary rehabilitation provides an effective tool for the
      treatment of patients with COPD. The whole-body rheographic technique can be used
      to evaluate the functional state of the patients and the efficiency of their
      rehabilitation.

PMID- 18822483
TI  - [Electropulse therapy in the early postoperative rehabilitation period after
      reconstructive and plastic surgery on fallopian tubes].
AB  - The efficiency of sinusoidal modulated currents applied to the vaginosacral
      region in the early postoperative rehabilitation period after plastic and
      reconstructive surgery on the fallopian tubes was assessed in 30 women aged from
      21 to 38 (mean 29.3+/-0.6) years. All of them had endoscopically diagnosed
      tubuloperitoneal infertility. Treatment with sinusoidally-modulated current in he
      early postoperative period had beneficial effect on the luteal phase of the
      menstrual cycle in 55.6%, on the hypothalamo-pituitary-ovarian axis in 23.3%, on
      hemodynamics in the small pelvis organs in 46.7%, on uterine tube activity in
      36.7%, and on the reproductive function in 30% of the patients. These women
      suffered tubuloperitoneal infertility for less than 5 years and underwent grade I
      II adhesive process in the absence of endoscopic signs of atrophic or hypetrophic
      changes in uterine tube walls.

PMID- 18822484
TI  - [Effect of low-intensity laser radiation on neutrophils from cervical discharge
      of women with mycoplasma infection].
AB  - Effect of low-intensity laser radiation on the main effector functions of
      neutrophils from the cervical discharge was studied in women with mycoplasma
      infection and dysfunction of neutrophil granulocytes manifest in the first place
      as a reduced number of phagocytic cells and decreased intensity of phagocytosis.
      The fraction of intracellular active forms of oxygen in cervical neutrophils from
      infected women was smaller than in healthy ones. Irradiation by low-intensity
      laser light increased both activity of pagocytosis and intracellular generation
      of active oxygen forms. It is concluded that low-intensity laser radiation
      normalizes disturbed neutrophil function.

PMID- 18822485
TI  - [Effect of spa-and-resort factors on the general well-being of practically
      healthy subjects].

PMID- 18822486
TI  - [Ultraphonophoresis using Tambukan peloid mud for the treatment of Chernobyl
      accident liquidators].

PMID- 18822487
TI  - [Effect of low-mineralized calcium-sodium sulfate hydrocarbonate Slavianovskaia
      mineral water on the metabolism in rats with experimental obesity].

PMID- 18822488
TI  - [Unilateral spinal anesthesia].

PMID- 18822489
TI  - [Monitoring and control of the parameters of respiratory mechanics during high
      frequency jet ventilation].

PMID- 18822490
TI  - [Role of paracetamol in a balanced postoperative analgesia scheme after
      thoracotomy].
AB  - The efficiency of paracetamol used in the balanced multimodal analgesia after
      thoracotomy still remains unclear. The prospective study covered 75 adult
      patients operated on the chest. The patients were randomized to 3 groups. They
      all received epidural autoanalgesia with a mixture of fentanyl (2 microg/ml) in
      0.2% ropivacaine solution and intramuscular injections of ketorolac, 30 mg, every
      8 hours. In Group 1 (n = 25), paracetamol was intravenously injected in a dose of
      4 g daily. In Group 2 (n = 23), rectal paracetamol was used in an equipotential
      dose. In Group 3 (n = 24), paracetamol was not given. Within the first 24
      postoperative hours, the severity of the pain syndrome and the incidence of
      adverse reactions of analgesia were estimated in all the patients. The obtained
      data were compared using Student's t-test and x2 test, by taking into account
      Bonferroni's correction. The p values of < 0.0017 were determined as
      statistically significant. The resting VAS did not differ between the groups. In
      cough, the severity of the pain syndrome was significantly less in Group 1 than
      in Groups 2 and 3. The use of the epidural mixture of ropivacaine and fentanyl
      required for adequate analgesia within the first 24 hours after surgery was much
      less in Groups 1 and 2 than that in Group 3. The high incidence of skin itch
      (20%) and urinary retention (8%) was observed in Group 3 (p < 0.017). No
      difference was found between the groups in the development of dyspepsia. The use
      of paracetamol in the postoperative multimodal analgesic therapy program after
      thoracotomy reduces the daily dose of epidurally administered ropivacaine and
      fentanyl with evident upgrade of analgesia quality, and the incidence of opioid
      induced adverse reactions.

PMID- 18822491
TI  - [Evaluation of the efficiency of using two different visual scales for
      quantitative measurement of acute pain].
AB  - The paper provides quantitative assessment of acute pain during the standard
      blood sampling procedure. The estimates of the impact of sex and age on the level
      of pain sensation were determined using two different visual scales in the
      evaluation of pain.

PMID- 18822492
TI  - [Topical aspects of standardization in anesthesiology and intensive care].
AB  - Implementation of standards and practice protocols is one of the most challenging
      problems of anesthesiology and intensive care. Several important issues regarding
      the process of standards development, their structure, goals, and targets,
      anticipated results and benefits, as well as clinical and theoretical limitations
      are discussed. The situation associated with the standardization at the national
      level is presented with parallel highlighting of future perspectives.

PMID- 18822494
TI  - [Seronin syndrome and cardiac arrest caused by high-dose moclobemide (case
      report)].
AB  - Serotonin syndrome is the syndrome resulting from brain tissue serotonin
      accumulation and accompanying by central nervous system dysfunction and
      circulatory collapse, which leads to a serious mortal danger to life. A female
      patient aged 31 years, diagnosed as having chronic psychosis in the history, was
      admitted to an intensive care unit in a critical state for having taking an
      increased moclobemide dose. The patient developed cardiac arrest and
      cardiopulmonary resuscitation (CPR) was initiated. A 15-minute CPR recovered
      sinus rhythm and pulse on the peripheral arteries of the limbs. When
      consciousness and respiration improved, the patient was weaned from resuscitation
      and extubated on the second day. On day 4, the patient was transferred from the
      intensive care unit to the department of psychiatry. The authors consider that
      patients with overdosage of antipsychotic agents at a risk for such serious
      complications, such as cardiac arrest, should be necessarily monitored in the
      intensive care unit.

PMID- 18822493
TI  - [Treatment of life-threatening airway obstruction in patients with malignant
      lymphomas].
AB  - Case histories of patients with hemoblastosis admitted to a hospital for acute
      respiratory failure due to tumor-induced obstruction were retrospectively
      analyzed. The causes of obstruction, antitumor therapy, methods for provision of
      airway patency, and major critical syndromes were analyzed. Ten patients with
      life-threatening tumor-induced airway obstruction were hospitalized from 1995 to
      2007. The patients suffered from malignant lymphomas in all cases. The causes of
      impaired airway patency were the compression of the trachea and large bronchi
      with a tumor, lymph nodes, affected thyroid, as well as the superior vena cava
      syndrome, and tumor-induced lesion of soft tissues of the neck and chest. Airway
      patency was effected with tracheal intubation in 9 cases, it was maintained by
      noninvasive mask ventilation in 1 patient. Translaryngeal tracheal intubation and
      tracheostomy were used for artificial ventilation (AV) in 6 and 3 patients,
      respectively. Multidrug therapy (MDT) was performed in all the patients. Airway
      patency restored in 9 patients after MDT initiation. The duration of AV was 5.8
      +/- l.7 days. The length of stay in an intensive care unit was 90%; intrahospital
      survival was 70%; 28-day and 3-year survivals were 90 and 24%, respectively. Two
      of the 3 patients who had undergone were observed to have serious complications
      (cicatrical stenosis, tracheoesophageal fistula). Hemoblastosis patients with
      tumor-induced obstruction need for provision of airway patency and for immediate
      initiation of MDT and/or radiotherapy. Orothracheal or nasotracheal intubation of
      the trachea is the methods of choice in providing airway patency. Tracheostomy is
      not indicated in most cases. Short-term prognosis is good in this cohort of
      patients. Long-term prognosis is determined by a lot of factors of which tumor
      sensitivity to cytostatics and radiation is most important.

PMID- 18822495
TI  - [Active forms of oxygen as a factor regulating surface characteristics of
      bacterial cells].
AB  - AIM: Effects of sublethal concentration of active forms of oxygen (hydrogen
      peroxide and hydroxyl radical) on cell surface properties of Escherichia coil,
      Staphylococcus aureus, Bacillus subtilis, and Klebsiella pneumoniae were studied.
      MATERIALS AND METHODS: Hydrophobicity of cell surface measured by transition of
      cells from water phase to hydrocarbomic phase and by the ability of bacteria to
      sorb lysozyme and hemoglobin. RESULTS: Treating of bacterial cells with hydroxyl
      radicals compared with hydrogen peroxide resulted in more marked decrease of
      bacteria's hydrophobicity and reduction of their ability to sorb on the surface
      the lysozyme and hemoglobin. Increasing of the number of R-forms in the bacterial
      population after contact with hydroxyl radicals was revealed. CONCLUSION: Active
      forms of oxygen generated in biological systems in concentrations which are not
      lethal for majority of microorganisms can regulate prokaryote and eukaryote
      interactions by changing their surface characteristics and therefore they are an
      ecologic factor determining forming and existence of microbial cenoses.

PMID- 18822496
TI  - [Phenotypic and genetic features of cultural-morphologic variants of Bacillus
      anthracis].
AB  - Comparative analysis of MVLA-genotypes of 6 Bacillus anthracis strains and 40
      their variants differing on capsule- and toxin synthesis, hemolytic, proteolytic
      and lecitinase activity, nutritional requirements, susceptibility to anthrax
      bacteriophages, virulence, immunogenicity, and presence of genes for capsule and
      toxin synthesis was performed. Results of phylogenetic analysis of 5 chromosome
      locuses and plasmid locus pXO1aat which are variable for this sample of B.
      anthracis cultures showed that all strains divided on 2 main clusters - A and B.
      Cluster A consisted of 5 genotypes whereas cluster B - of 1 genotype. All highly
      virulent original strains and variants with characteristic phenotype
      Cap(CO2)(+)(O2)(-)Tox(+)ProtA(+)Hly(+) Lec(-)Trp(+) had identical genotype in 4
      groups and in 5th group differences were present only in vrrA locus. All original
      strains and variants with the most atypical complex of phenotypic characteristics
      Cap (CO2)(+)(O2)(+)Tox(-)ProtA(-)Hly(-)Lec(-)Trp(-) also had the same genotype
      belonging to cluster B and diverged on characteristic of 5 chromosomal VNTR
      locuses and pXO1aat locus from typical strains. Absence of toxin production in
      vitro was not related to loss of genetic determinants of toxin components.
      Cultures with typical characteristics, one of which was ability to produce toxin
      in vitro, had larger sizes of amplicons of pXO1aat locus (135 and 132 nbp),
      whereas atoxigenic original strains and variants with complex of atypical
      characteristics and identical chromosome genotype had the smallest sizes (123
      bnp). All original cultures were isolated in Russia, their genotypes are
      described for the first time.

PMID- 18822497
TI  - [Protective activity of secreted proteins of Streptococcus pneumoniae and
      Klebsiella pneumoniae].
AB  - Protective efficacy of secreted proteins of Streptococcus pneumoniae and
      Klebsiella pneumoniae cultivated on cardiocerebral broth and semisynthetic growth
      medium respectively was studied in vivo. Fraction with molecular weight 30 - 50
      kDa obtained by the method of membrane fractionation had high protective
      efficacy. Two-dose immunization of mice with this fraction provided 80 - 100%
      protection from infection by homologous strains of S. pneumoniae and K.
      pneumoniae. Cross-protective activity of the fraction was revealed when infecting
      immunized mice by different K-types of K. pneumoniae. Blood sera of mice
      immunized with 30 - 50 kDa fraction possessed preventive features protecting from
      infection 90% of animals while 100% of death in the control group. It was
      determined that protective efficacy of the mentioned fraction was determined by
      protein-containing antigens because proteolytic disruption of the protein
      component resulted in loss of protective properties of the preparation.

PMID- 18822498
TI  - [Vaccination of children born from HIV-infected mothers against Haemophilus
      influenzae type b infection].
AB  - Course of postvaccinal period after injection of vaccine against Haemophilus
      influenzae type b administered simultaneously with vaccines of Russian national
      immunization schedule was studied in children born from HIV-infected mothers.
      Good tolerability of the vaccine administered concomitantly with diphtheria
      tetanus-whole cell pertussis and inactivated polio vaccines (Imovax Polio), which
      is comparable with tolerability in healthy children, was demonstrated.
      Prevaccination titers of antibodies and their dynamics during immunization
      process were described. Increase of levels of antibodies was detected both in the
      group of children with perinatal contact with HIV infection and in the group of
      HIV-infected children.

PMID- 18822499
TI  - [Chronic HCV-infection and expression of mRNA of CC-chemokines and their
      receptors].
AB  - The aim of this study was to evaluate some patterns in expression of CC
      chemokines (MIP-1alpha, MIP-1beta, MCP-1, RANTES) and their receptors (CCR1,
      CCR2, CCR3, CCR5) in peripheral blood leukocytes and liver biopsy samples from 21
      patients with chronic hepatitis C. 10 healthy subjects were included in the
      control group. In patients with chronic HCV-infection significant increase of MCP
      1 mRNA in liver tissue was observed as the disease progressed. Moreover, content
      of MCP-1 mRNA was significantly higher in liver as compared with blood. Level of
      MCP-1 mRNA in liver was directly related with histological changes. Levels of
      mRNA of CCR1, CCR2, CCR3, and CCR5 in blood of patients with minimal histological
      manifestations of chronic HCV-infection were significantly lower than in patients
      with more marked lesions. Expression of CCR1 and CCR5 mRNA in blood was directly
      correlated with histological activity index and degree of fibrosis. Conducted
      study demonstrates that progression of chronic hepatitis C is realized through
      local activation of MCP-1 mRNA synthesis leading to systemic response which
      manifested by increase of expression of CCR1, CCR2, CCR3, and CCR5 in peripheral
      blood leukocytes.

PMID- 18822500
TI  - [Phenotypic and genotypic identification of bacteria from the Burkholderia
      cepacia complex].
AB  - AIM: Evaluation of the diagnostic value of pheno- and genotypic characteristics
      of B. cepacia strains collection. MATERIALS AND METHODS: Phenotypic and genetic
      methods of identification and differentiation of 25 strains of the B. cepacia
      complex. RESULTS: Polyphasic taxonomic approach utilizing multiple diagnostic
      tests was used for accurate identification of Burkholderia species. Algorithm for
      identification of microorganisms from the B. cepacia complex was developed.
      CONCLUSION: Combined use of phenotypic and molecular genetic tests, such as recA
      gene PCR, is recommended for differentiation of the B. cepacia complex
      genomovars.

PMID- 18822501
TI  - [Microflora of gastrointestinal tract in patients with chronic cholecystitis].
AB  - AIM: Assessment of quantitative and qualitative characteristics of
      gastrointestinal microflora in patients with chronic cholecystitis. MATERIALS AND
      METHODS: Bacteriological analysis of biopsy samples of esophageal and gastric
      mucosae as well as stool samples was performed in 10 healthy volunteers and 28
      patients with chronic cholecystitis. RESULTS: Opportunistic microorganisms are
      acquiring greater significance in formation of gastrointestinal microbiocenosis.
      Significant increase of both isolation rate and density of gastrointestinal tract
      colonization by staphylococci, enterobacteriae and anaerobic microorganisms was
      revealed. CONCLUSION: Obtained results showed abnormalities of microbiocenosis of
      esophageal and gastric mucosae and presence of intestinal disbacteriosis of
      different degrees of intensity.

PMID- 18822502
TI  - [Current characteristics of natural nidality of tick-borne encephalitis: new or
      well forgotten?].
AB  - A number specialists' opinion as to which the rise in the incidence of tick-borne
      encephalitis at the turn of the centuries is due to the new features of the
      epidemiology of this infection and to global climatic changes is analyzed. There
      are no objective evidence suggesting the ongoing expansion of a natural habitat
      of the major vectors--taiga (Ixodes persulcatus) and wood (I. ricinis) ticks and
      the noticeable increase in their size and virus infection rates. The notion of
      the recent penetration of ticks into the metropolises where natural focuses have
      emerged and human beings are infected is inconsistent with the multidescribed
      facts. There is no significant evidence for the expansion of a nosoarea of
      tickborne encephalitis. The impact of reformed anthropurgic foci and that of the
      proportion of town-dwellers in the general structure of morbidity on the epidemic
      situation have been evaluated. The intensity of an epidemic manifestation of
      natural foci is always determined by two most important parameters: 1) the
      loimopotential of foci and 2) the intensity of the population's contact with
      them. The nature of an interaction between these factors, which has caused a
      rapid surge of morbidity rates and their subsequent long-time reduction, is
      considered.

PMID- 18822503
TI  - [Study of the emotional-and-personality sphere in patients with psoriasis
      concurrent with chronic opisthorchiasis].
AB  - The study was undertaken to evaluate the emotional-and-personality sphere in
      patients with psoriasis concurrent with chronic opisthorchiasis (CO). A hundred
      and fifty patients with psoriasis concurrent with CO, 100 psoriatic patients
      without helminthiasis, 100 patients with CO, and 30 healthy individuals were
      examined. The SMOL test was used to evaluate the emotional-and-personality
      sphere. Clinical and psychological studies of patients with psoriasis alone and
      in combination with CO revealed unidirectional psychoemotional (mainly
      hypochondriacal) changes in patients in these groups. However, anxiety and
      hypochondriac disorders were clinically significant in patients with comorbidity
      (psoriasis + CO). This suggests that Opisthorchis invasion is of considerable
      importance in the genesis of these changes and requires medical correction of
      helminthiasis.

PMID- 18822504
TI  - [Anopheles mosquitoes (Diptera, Culicidae) of the Tien Shan: morphological,
      cytogenetic, and molecular genetic analysis].
AB  - Morphological, cytogenetic, and molecular genetic studies of the Anopheles fauna
      in the valley and foothills of the Tien Shan identified 5 species of malaria
      mosquitoes: An. artemievi Gordeev et al., An. messeae Fall, An. claviger Meigen,
      An. hyrcanus Pallas, An. pulcherrimus Theobald, and superpictus Grassi. An.
      claviger, An. hyrcanus, and An. messeae were prevalent in the Northern Tien-Shan.
      An. artemievi, An. claviger, An. hyrcanus, An. messeae, and An. superpictus were
      detected in the Western Tien Shan. An. artemievi was first recorded in
      Kazakhstan. An. artemievi, An. claviger, and An. superpictus were noted in the
      Inferior Tien Shan. An. messeae was first observed in the Issyk Kul hollow. An.
      artemievi, An. claviger, and An. superpictus were habitants of the foothills of
      the South-Western Tien Shan. An. artemievi, An. hyrcanus, An. superpictus, and
      An. pulcherrimus were in the plain. An. pulcherrimus and An. superpicts
      mosquitoes are regarded as important vectors in the new malaria foci of the
      Fergana regions. The role of An. artemievi in the transmission of malaria is to
      be specified.

PMID- 18822505
TI  - [Malaria elimination monitoring and assessment].

PMID- 18822506
TI  - [Role of fleas, the principal and secondary plague vectors, in the circulation of
      the causative agent in Siberian natural foci].
AB  - The paper reviews data on the role of fleas as the principal and secondary
      vectors of infection in the Siberian natural foci of plague. The role of
      Citellophilus tesquorum as the principal plague vectors in the Transbaikalian and
      Tuvinian natural foci is shown to be determined by their ecological
      characteristics (the degree of specificity to the main host, numbers, and natural
      infection) to a greater extent and by the rate of block formation to a lesser
      extent. The significance of principal and secondary vectors is estimated in the
      circulation of the causative agent in the monovectoral (Transbaikalian and
      Tuvinian) and multivectoral (Gorno-Altai) foci of plagues. It is suggested that
      the "microfocal" form (phenotype) of the agent's existence is characteristic of
      the Siberian natural foci where the rate of block formation does not generally
      show high indices. This phenomenon might be a basis for the long circulation of
      the plague microbe in the mountain (Tuva and Gorno-Altai) foci where protracted
      interepizootic periods have not been registered.

PMID- 18822507
TI  - Slow rehabilitation of drug-coated stents. New research supports the safety of
      drug-coated stents, but they aren't for everyone.

PMID- 18822508
TI  - Don't delay when heart failure threatens. Ignoring the warning signs of worsening
      heart failure can get you into big trouble.

PMID- 18822509
TI  - A second look at beta blockers and blood pressure.  A beta blocker alone isn't
      usually the best choice for simple, uncomplicated high blood pressure.

PMID- 18822510
TI  - Seeing the heart with sound.  Ultrasound-based echocardiograms yield ultra images
      of the heart.

PMID- 18822511
TI  - Warfarin home monitoring program expanded.

PMID- 18822512
TI  - Ask the doctor.  I want to donate blood, but I faint or come close to it nearly
      every time I have blood drawn at the doctor's office.  Can I do anything to keep
      myself from fainting?

PMID- 18822513
TI  - Home defibrillators may save lives, but aren't for everyone.  AEDs provide
      reassurance, but CPR may be just as effective.

PMID- 18822514
TI  - Recurrent clots can be prevented inside stents.  Controlling your risk factors
      and adhering to anticoagulation therapy can help you stay healthy after stent
      placement.

PMID- 18822515
TI  - Combination drug may be best for treating hypertension.  Two medications in one
      pill help lower blood pressure and significantly reduce the risk of potential
      cardiovascular events.

PMID- 18822516
TI  - I was told to stop taking my daily betablocker (Coreg)before a myocardial
      perfusion test.  I was hospitalized with chest pain and a bout of atrial
      fibrillation.  I have cardiomyopathy and was prescribed amiodarone and warfarin,
      but I stopped taking them when I learned of their side effects.  Was it wrong to
      stop taking the Coreg?

PMID- 18822517
TI  - Treating prostate cancer, Part V: radiation therapy.

PMID- 18822518
TI  - Chronic constipation: a strain for men.

PMID- 18822519
TI  - On call. Ever since I retired last year, I've enjoyed taking an afternoon nap
      whenever it's convenient. My wife says napping will turn me into an old man. I
      can easily give up my naps if she is right--but is she?

PMID- 18822521
TI  - Health tips.  Get the most from a complete checkup.

PMID- 18822520
TI  - By the way, doctor.  My ophthalmologist says I have drusen scattered over the
      macula in both eyes and wants to check them every nine months.  Could you say
      something about what drusen are and what they mean?

PMID- 18822522
TI  - Study suggests vitamin D may play role in arterial disease.

PMID- 18822523
TI  - Dual energy X-ray imaging.  Two is better than one.

PMID- 18822524
TI  - Thyroid nodules.  A lump in the neck.

PMID- 18822525
TI  - I recently visited a large medical center for a second opinion. I brought along
      results from an MRI done at my local hospital, but was told I'd need to have
      another MRI. Why was that necessary?

PMID- 18822526
TI  - Have the heart for fish oil?

PMID- 18822527
TI  - Drink to good health?  More findings on alcohol.

PMID- 18822529
TI  - Infection after joint replacement surgery.

PMID- 18822528
TI  - Care for the caregivers:  how to find it.

PMID- 18822530
TI  - Study shows benefit of hypertension help after 80.

PMID- 18822531
TI  - My 10-year colonscopy is coming up.  Should I request a virtual colonscopy?

PMID- 18822532
TI  - [Enjoying life in studying, teaching and researching].

PMID- 18822533
TI  - Morbidity due to obstructive sleep apnea: insights from animal models.
AB  - PURPOSE OF REVIEW: Obstructive sleep apnea (OSA) is a prevalent disorder with
      clinically well known mid-term and long-term consequences. It is difficult,
      however, to investigate the mechanisms causing morbidity in OSA from human
      studies, owing to confounding factors in patients. Animal research is useful to
      analyze the various injurious stimuli--intermittent hypoxia/hypercapnia,
      mechanical stress and sleep disruption--that potentially cause OSA morbidity.
      This review is focused on the most recent advances in our understanding of the
      consequences of OSA, achieved as a result of animal models. RECENT FINDINGS:
      Animal research has improved our knowledge of various aspects of the
      cardiovascular consequences of OSA: myocardial damage, left ventricular
      dysfunction, vasoconstriction, hypertension and atherosclerosis. The systemic and
      metabolic consequences of OSA--inflammation, insulin resistance, alterations in
      lipid metabolism and hepatic morbidity--have also been investigated with animal
      models. Our understanding of the mechanisms involved in the neurocognitive
      consequences of OSA--neuronal and brain alterations and cognitive dysfunctions-
      has also been improved through animal research. Moreover, animal models have
      recently been used to investigate the mechanisms of upper airway inflammation and
      dysfunction. SUMMARY: The simple experimental models used to investigate OSA
      morbidity are useful for investigating isolated mechanisms. However, more complex
      and realistic models incorporating the various injurious challenges
      characterizing OSA are required to more precisely translate the results of animal
      research to patients and to design potentially preventive and therapeutic
      strategies.

PMID- 18822534
TI  - [Punishment versus reconciliation: marriage control in 16th- and 17th-century
      Holland].

PMID- 18822535
TI  - Baltic Dental and Maxillofacial Journal: quality of the journal.

PMID- 18822536
TI  - The labyrinth and the pit.

PMID- 18822538
TI  - Do dress codes lead to discrimination?

PMID- 18822539
TI  - 'We must find a solution to the neonatal nursing crisis'.

PMID- 18822540
TI  - Champions of equal rights.

PMID- 18822541
TI  - A pledge on cancer care.

PMID- 18822542
TI  - Guidelines outline key actions to improve infection control.

PMID- 18822543
TI  - Exploring the anatomy and physiology of ageing. Part 6--the eye and ear.

PMID- 18822544
TI  - Acute respiratory failure 1: assessing patients.
AB  - This is the first in a two-part unit on acute respiratory failure. Part 1
      explores respiratory failure and its causes and identifies ways of recognising
      patients in acute respiratory failure.

PMID- 18822545
TI  - A controversial jab or a wonderful opportunity?

PMID- 18822546
TI  - Exploring the evidence for screening staff for MRSA.
AB  - Christine Perry reviews the current evidence for screening staff for MRSA and the
      issues to be considered when screening identifies positive members of staff.

PMID- 18822547
TI  - The epidemiology and burden of HPV disease.
AB  - Margaret Stanley describes what human papillomavirus is and how it causes
      disease. She also outlines how the new vaccine to protect against HPV works.

PMID- 18822548
TI  - How to evaluate sharp safety-engineered devices.
AB  - With increasing concerns of occupational exposure to bloodborne viruses in
      healthcare settings, NHS trusts are under pressure to consider opting for safer
      sharps devices that are designed to protect users from needlestick injuries.
      However, with an ever-increasing range of 'sharp safety' devices on the market,
      deciding what to purchase is a complex issue. In addition, evidence shows that
      purchasing safety devices alone will not eliminate the problem of needlestick
      injuries. This article discusses the criteria that should be taken into account
      when trusts consider introducing sharp safety devices into their workplace.

PMID- 18822549
TI  - Why have evidence if it's really money that matters?

PMID- 18822552
TI  - Correction to smoking article.

PMID- 18822553
TI  - Empowering people to manage their cancer experience. Interview by Anne
      Manchester.

PMID- 18822554
TI  - Returning home to care for a dying mother.

PMID- 18822555
TI  - Helping dying patients transition to another realm.

PMID- 18822556
TI  - Walking beside those with cancer. Interview by Teresa O'Connor.

PMID- 18822557
TI  - Assessing patients' spiritual needs.

PMID- 18822558
TI  - Reflective practice. AIDS critical thinking.

PMID- 18822559
TI  - Looking back and forward at Labour's industrial relations record. Interview by
      Jock Lawrie.

PMID- 18822560
TI  - I didn't know--a defence or not?

PMID- 18822561
TI  - Safe staffing--getting it right now.

PMID- 18822562
TI  - The role of culture in determining wellness.

PMID- 18822563
TI  - Survey reveals extent of bullying.

PMID- 18822564
TI  - Unlevel playing field? Hospitals contend ASCs getting off easy.

PMID- 18822565
TI  - Tormented by the RAC. Hospitals, lawmakers challenge audit program.

PMID- 18822566
TI  - The socialization of risk. Medicare debate, bailouts speak volumes about
      corporate, government recklessness.

PMID- 18822568
TI  - Joining hands. Legal, operational issues prove tricky as providers collaborate on
      technology.

PMID- 18822567
TI  - A sense of urgency is needed. Solutions on long-term care demand action now.

PMID- 18822569
TI  - Medicaid's hard lessons. Teaching hospitals learn to cope with complexities.

PMID- 18822570
TI  - Children in immigrant families impact health care system. Pennsylvania has almost
      a quarter of a million.
AB  - 15.7 million U.S. children (including almost a quarter of a million Pennsylvania
      children) live in immigrant families. These newest arrivals are becoming a
      critical component of the changing demographics of the state's (and nation's)
      evolving population. A complex set of economic, social and cultural factors
      affect these youngsters and their families, which in turn can impact on the
      delivery of health services.

PMID- 18822571
TI  - Exit strategies.

PMID- 18822572
TI  - Basics of investing.

PMID- 18822573
TI  - Scooters: a smoother, sleeker ride.

PMID- 18822574
TI  - Stand for health.

PMID- 18822575
TI  - The complexity of walking.

PMID- 18822576
TI  - What price fitness?

PMID- 18822577
TI  - Conquering back pain.

PMID- 18822578
TI  - Paper or plastic.

PMID- 18822579
TI  - Recovering lost function.

PMID- 18822580
TI  - Present on admission overview.

PMID- 18822581
TI  - Funding deficiencies, overcrowding create lack of access to care for mental
      health patients.

PMID- 18822582
TI  - Georgia's growing crisis goes largely unnoticed.

PMID- 18822583
TI  - A call to unity.

PMID- 18822584
TI  - Global HIV/AIDS funding expanded to $50 billion.

PMID- 18822585
TI  - Preconception care: ensuring healthier pregnancies.

PMID- 18822586
TI  - Did this young girl brush too vigorously?

PMID- 18822587
TI  - Antenatal depression: guidelines for when to use pharmacotherapy.

PMID- 18822588
TI  - VATS lobectomy to treat early-stage non-small cell lung cancer.

PMID- 18822589
TI  - What to do when neck pain is more than just a simple pain in the neck.

PMID- 18822590
TI  - A call to compassion.

PMID- 18822591
TI  - Urinary incontinence and sarcoidosis.

PMID- 18822592
TI  - When the patient asks. How can I lower my cholesterol?

PMID- 18822593
TI  - These characteristic findings reveal a rare disease.

PMID- 18822594
TI  - Case of the month. Subacute stent thrombosis with classic symptoms of angina.

PMID- 18822595
TI  - Health care made simple.

PMID- 18822596
TI  - A plea for my daughter.

PMID- 18822597
TI  - The genetic detectives.

PMID- 18822598
TI  - The myths of teen sex.

PMID- 18822599
TI  - A sperm-biz overhaul.

PMID- 18822600
TI  - How to get a leg up for fitness.

PMID- 18822601
TI  - Why only-children rule.

PMID- 18822602
TI  - [Fetal responses to different methods of electrocution of pregnant sows].
AB  - The fetal stress responses in sows euthanized by electrical current during their
      second and last trimester of pregnancy (G1 and G2) were evaluated. Three methods
      of euthanasia of pregnant sows generally applicable to cases of epizootic or
      emergency slaughter were investigated: 1. conventional application of electrical
      current to the head and heart (HH); 2. application of electrical current to the
      head, heart and the uterus (HHU); 3. application of electrical current to the
      head, heart and from the upper body to the vagina (HHV). Fetuses were delivered
      by cesarean section at intervals of 3 to 4 minutes and remained attached to the
      sow by the umbilical cord. Fetal vitality, reflexes, heart rate, blood pressure,
      rectal body temperature, intracardial arteriovenous pCO2, pH and lactic acid were
      monitored for a period of 30 minutes. No method was found to kill the fetal pigs
      immediately. In fetuses at G1 there were no significant differences between the
      HH and HHU and HHV methods. Fetuses at G2 showed a significantly faster decrease
      in heart rate and blood pressure as well as a shorter period of time for the
      absence of fetal body movements and reflexes for the HHT method, compared to the
      other methods. Since it is not yet known to what extent the fetal pig experiences
      pain and suffering, the prolonged process of dying for the in utero fetus due to
      hypoxia which includes struggling and gasps is inconsistent with criteria for
      humane euthanasia and animal welfare.

PMID- 18822603
TI  - Response to a combined treatment program with clomipramine, behavioral, and
      environmental management of compulsive tail chasing in a German Shepherd.
AB  - A 15-month-old female German Shepherd dog showing compulsive tail chasing was
      treated with a treatment protocol of pharmacological therapy (using clomipramine)
      in conjunction with behavioral and environmental management. The responses to the
      treatment protocol were assessed once a week for 7 weeks in respects to
      behavioral conditions and the frequency of bouts and its duration. The behavior
      history including mother, father, and her littermates were also evaluated for the
      apparent diagnosis. The compulsive tail chasing of the patient dog was improved
      on the aspect of behavioral condition and gradually decreased in the frequency
      and duration of bouts. However, in the mid of treatment, the animal showed an
      aggressive behavior as a concurrent sign associated with compulsive tail chasing.

PMID- 18822604
TI  - [Antibody response after immunization with a Salmonella Typhimurium live vaccine
      in dependence on the way of application].
AB  - In Germany now, the recognition of Salmonella infections in pig herds is based on
      three different commercial tests detecting antibodies against Salmonella-derived
      lipopolysaccharide (LPS). However, a serious disadvantage of these tests, used so
      far, is the restricted detection of antibodies belonging predominantly to the
      immunoglobulin class g (IgG). Therefore, a new test was developed to detect three
      Ig classes (IgM, IgG and IgA). Different constellations between the three Ig
      classes allow the evaluation of the current infection status of each pig. Under
      field conditions, this was proved in three different vaccination trials using a
      commercial Salmonella Typhimurium live vaccine.

PMID- 18822605
TI  - [Investigations on the antioxidative metabolism during the periparturient period
      in dairy goats with special regard to seasonal differences in feeding and
      management].
AB  - In a herd of 1400 dairy goats with an average milk yield of 840 kg/year, 40
      "Weisse Deutsche Edelziegen" (October-January: n = 19; April-July: n = 21) were
      examined. Venous blood samples were collected 6-8, 3-4 and < 2 weeks (wks) ante
      partum (a. p.) and 2-4 days (d), 3-4 and 6-8 wks post partum (p. p.).
      Antioxidative Capacity of Water soluble substances (ACW) and Trolox Equivalent
      Antioxidative Capacity (TEAC) were measured in serum; activities of superoxide
      dismutase (SOD) and glutathione peroxidase (GPX) were measured in an erythrocyte
      pellet and in whole blood. ACW and TEAC increased significantly 3-4 wks p. p. In
      summer these two parameters showed significantly higher concentrations than in
      winter. The SOD had a significantly higher activitiy < 2 wks a. p. and 6-8 wks p.
      p. GPX-activity showed a constant increase from the beginning of investigations
      and from 3-4 wks p. p. up to the end of investigations activities were
      significantly higher than 6-8 wks a. p. The samples ante partum and the first
      sample taken post partum showed significantly higher activities in summer than in
      winter. The present study shows, that the metabolic challenge associated to the
      periparturient period in combination with changing capacity of food intake,
      influences the antioxidative metabolism in dairy goats. Seasonal depending
      changes on feeding quality and climate (barn temperature, quality of feeding
      components) also influence this system.

PMID- 18822606
TI  - [Familial canine pituitary-dependent hyperadrenocorticism in wirehaired
      Dachshunds].
AB  - Canine pituitary hyperadrenocorticism (Cushing's disease) caused by neoplasia of
      the corticotrope cells is one of the most common endocrine diseases especially in
      smaller dog breeds. Cushing's disease was diagnosed in eleven wire-haired
      Dachshunds and for further six wire-haired Dachshunds Cushing's disease was
      suspected on the basis of clinical signs. A joined pedigree could be ascertained
      for all these 17 dogs. Eleven of these dogs were so closely related to each
      other, that they were summarized in four nucleus families. Two fullsiblings were
      examined by means of clinical, laboratory diagnostic and morphological methods.
      The main lesions consisted of atrophic dermatosis with alopecia, increase of
      activity of liver enzymes in plasma and bilateral adrenocortical hyperplasia and
      therefore corresponded to the typical signs of a secondary hyperadrenocorticism.
      A rather unusual finding was the pituitary carcinoma in one of these dogs.
      Similarly to human patients affected by hyperadrenocorticism, real-time PCR
      analysis showed a 2.9-fold increase of expression of the canine MDR1 gene in the
      liver of one affected wirehaired Dachshund. This study documents the first
      familial occurrence of pituitary-dependent hyperadrenocorticism in wirehaired
      Dachshunds, the overexpression of the MDR1 gene in the dog and the third case of
      familial hyperadrenocorticism in dogs ever described.

PMID- 18822607
TI  - [Estimation of genetic parameters for radiographic signs of hip dysplasia in
      Labrador Retrievers].
AB  - The aim of this study was the analysis of environmental factors and estimation of
      genetic parameters for hip dysplasia in Labrador Retrievers. We analysed hip
      dysplasia scores of 2970 dogs from the official screening programme of the
      Labrador Club Deutschland (LCD) according to the FCI protocols. Traits evaluated
      were HD-Mit (average value of HD scores), HD-Max (higher score of both hip
      joints), HD-LI and HD-RE (HD score of the left or right hip joint). A linear
      animal model was employed to estimate heritabilities, additive genetic and
      residual correlations using Residual Maximum Likelihood (REML). Only inbreeding
      was significant after testing all non-genetic effects. Higher inbreeding
      coefficients were associated with higher HD scores. Heritability estimates and
      their standard errors were 0.38 +/- 0.04 for HD-Mit, 0.40 +/- 0.04 for HD-Max,
      0.33 +/- 0.03 for HD-LI and 0.38 +/- 0.04 for HD-RE. The additive genetic
      correlation between HD-LI and HD-RE was 1. Heritability for female dogs was 0.31
      and 0.30 for male dogs. The analysis of HD scores of Labrador Retrievers showed
      that the highest HD score of the hips should be used in breeding programmes, that
      heritabilities are not different among females and males, and that genetic
      components are much more important than environmental factors.

PMID- 18822608
TI  - [Pyothorax in 26 cats: clinical signs, laboratory results and therapy (2000
      2007)].
AB  - Common historical findings in 26 cats with pyothorax were dyspnea (85%), lethargy
      (65%), and anorexia (62%), common clinical findings were dyspnea (89%), tachypnea
      (73%), fever (39%), and hypothermia (27%). Frequent laboratory abnormalities were
      leukocytosis (68%) with a left shift (100%), anemia (65%), hypoalbuminemia (91%),
      hyperglobulinemia (86%), hyperbilirubinemia (60%) as well as azotemia (52%). The
      thoracic effusion was purulent in all cats, the thoracic fluid evaluation (n =
      19) met the criteria for an inflammatory exudate (protein 32-63 g/l, median 44;
      cell count 54.4-390 x 10(9)/l, median 100). Cytological analysis revealed
      bacteria in 21 of 24 cats. From 16 cats 13 different genera were isolated, 5
      cultures were without bacterial growth. In 12.5% of the cats a single population
      of bacteria was identified, and in 87.5% a mixture of 2-4 different bacterial
      species were cultured. Obligate anaerobic bacteria were the most common isolates
      (70%) followed by facultative anaerob (22.5%) and aerob growing (7.5%) bacteria.
      Bacterial culture most often yielded Fusobacteria spp., Prevotella spp.,
      Pasteurella spp., Porphyromonas spp. and Bacteroides spp. Three cats were
      euthanized at the day of presentation. A thoracic lavage was performed in 22
      cats; mechanical complications with the chest tubes occured in 4 cats.
      Thoracotomy was performed in 2 cats. Of the 23 treated cats 17 survived (74%).

PMID- 18822609
TI  - [Viscosity determination of synovial fluids from the canine hip and elbow joint
      as well as the human knee joint].
AB  - The development of pathological changes in both human and canine hip joints is
      mainly caused by a lack of synovial fluid lubrication. This results in an
      increased joint abrasion. Even after implantation of joint prosthesis, inadequate
      lubrication can lead to abrasion in the tribological pair. This can finally
      result in aseptic loosening of the prosthesis. In spite of the enormous number of
      studies that have been performed on human, only little knowledge about the
      tribological properties of the joints in dogs is available in the literature. For
      this reason the viscosities of synovial fluid, derived from physiological and
      pathologically changed canine elbow joints were measured. The viscosities were
      determined by the use of a cone-plate viscometer at different temperatures and
      shear rates. The obtained values were compared with the viscosity values of
      pathologically changed synovial fluids from human knee joints as well as with
      pathological samples from the canine hip joint. The results show that the
      viscosity values vary within a series of measurements and are inversely
      proportional to the temperature of the sample and the shear rate. The differences
      between the average viscosities of canine and human synovial fluids taken from
      pathologically changed joints are below 4% (22.5 s(-1) at theta1 = 25 degrees C).
      The findings of this study are being implemented in a FE-Model for the
      computation of actual forces in the hip joint during different movements. This
      would represent a contribution to an improved prosthetic treatment of canine and
      human hips.

PMID- 18822610
TI  - An Rx to push generic drugs.

PMID- 18822611
TI  - Sad brain, happy brain.

PMID- 18822612
TI  - Neurotransmitters 101.

PMID- 18822613
TI  - Sing, brain sing.

PMID- 18822614
TI  - My mother's case of 'pleasant dementia'.

PMID- 18822615
TI  - Mysteries of memory.

PMID- 18822616
TI  - Is morality natural?

PMID- 18822617
TI  - Silent demons.

PMID- 18822618
TI  - XDR-TB in India : when will we heed the alarm?

PMID- 18822619
TI  - Prevalence and predictors of pulmonary artery hypertension in systemic sclerosis.
AB  - INTRODUCTION: Development of pulmonary artery hypertension (PAH) worsens the
      prognosis of systemic sclerosis (SSc). There is paucity of data on PAH in
      patients with SSc in India. We have attempted to determine the prevalence and
      predictors of pulmonary artery hypertension in systemic sclerosis using
      noninvasive cardiopulmonary evaluation. OBJECTIVES: (1) To study the prevalence
      of PAH in SSc (2) To study the predictors of PAH in SSc (gender, age of onset of
      disease, duration of disease, extent of skin involvement, digital infarcts/ulcer,
      interstitial lung disease. MATERIAL AND METHODS: Clinical and functional
      characteristics of 100 patients of systemic sclerosis who had undergone screening
      echocardiography to detect pulmonary artery hypertension were studied. RESULTS:
      PAH was found in 32% patients on 2D-echocardiography. Prevalence of PAH did not
      differ between patients with limited cutaneous SSc (lcSSc) and patients with
      diffuse cutaneous SSc (dcSSc). On multiple logistic regression analysis, none of
      the studied variables was found to be independent predictor of PAH in SSc.
      CONCLUSION: PAH in SSc occurs in significant proportion of patients without any
      "red flag signs" in early stages. Non-invasive screening of patients with SSc for
      PAH will help in early diagnosis and appropriate timely therapeutic intervention
      before significant end-organ damage occurs.

PMID- 18822620
TI  - Efficacy of teriparatide in increasing bone mineral density in postmenopausal
      women with osteoporosis--an Indian experience.
AB  - BACKGROUND AND OBJECTIVE: Osteoporosis is emerging as a leading cause of
      substantial morbidity in India, particularly in postmenopausal women.
      Teriparatide (recombinant human parathyroid hormone [1-34]) increases bone
      formation and improves bone microarchitecture, thereby reducing the risk of
      fractures. This study was conducted to evaluate the efficacy of teriparatide in
      increasing bone mineral density (BMD) in postmenopausal women with osteoporosis.
      MATERIAL AND METHODS: A randomised, prospective, multicentre, open-label,
      controlled study was conducted on 82 postmenopausal women with established
      osteoporosis. Patients were randomly divided into control and teriparatide
      groups, each group consisting of 41 patients. All the patients were supplemented
      with 1000 mg of elemental calcium and 500 IU of vitamin D throughout the study
      period of 180 days. Besides, teriparatide group patients were administered
      teriparatide 20 microg daily subcutaneously. Lumbar spine, femoral neck and total
      hip BMD, bone mineral content (BMC) and bone area were measured by dual energy x
      ray absorptiometry (DXA) at baseline and at the end of 6 months of treatment.
      Bone biomarkers, such as serum bone specific alkaline phosphatase (BSAP) and
      serum osteocalcin (OC), representing bone formation, and urinary
      deoxypyridinoline (DPD), representing bone resorption were assessed at baseline,
      and at 3 and 6 months of treatment. RESULTS: During the study period, 9 patients
      (11%) were lost to follow-up--6 in control group (7.3%) and 3 in teriparatide
      group (3.7%). There was an excellent compliance to both oral and injectable
      medication. The investigational product teriparatide was well tolerated and there
      were no serious adverse events. In addition, there were no significant
      differences between the groups in the incidence of adverse events. The percentage
      of increase in lumbar spine BMD, which is the primary endpoint, was significantly
      (P < 0.001) higher in teriparatide group compared to that in control group (6.58%
      vs. 1.06%). Further, teriparatide significantly increased percentage of change in
      lumbar spine T-score (P < 0.001), BMC (P < 0.001) and bone area (P < 0.028)
      compared to control group at 6 months. Administration of teriparatide resulted in
      a significant percentage of increase in all the bone biomarkers in teriparatide
      group compared to control group patients at 3 and 6 months over baseline, thereby
      showing that there was a significant increase in bone turnover in teriparatide
      group of patients. CONCLUSION: These results show that teriparatide is an
      effective and safe drug in increasing the BMD and therefore, teriparatide
      provides yet another new therapeutic option for reducing the risk management of
      osteoporosis in postmenopausal women (clinicaltrials.gov number, NCT00500409).

PMID- 18822621
TI  - Transjugular liver biopsy using Tru-cut biopsy needle: KEM experience.
AB  - BACKGROUND AND AIM: Transjugular liver biopsy is accepted procedure in patients
      in whom percutaneous liver biopsy is contraindicated. We report our experience
      with this procedure, its indications, efficacy and safety in Indian population
      over 5 years. MATERIAL & METHODS: A retrospective study of 145 consecutive
      patients who had undergone transjugular liver biopsy from May 2002 to Nov. 2007
      was done from the database maintained in our department. We evaluated the
      indications, technical success, complication and impact of histological diagnosis
      on the management of those patients. RESULTS: 145 Transjugular liver biopsies
      were performed of which 74 were males and 71 were females aged between 5 and 74
      years. Two procedures were abandoned due to failed hepatic vein cannulation
      because of venous occlusion. Out of 143 biopsies, 4 were inadequate while 139
      yielded adequate tissue for histopathological diagnosis. Histopathological
      examination in our study showed cirrhotic changes in 56, hepatitis including both
      acute and chronic in 48, periportal fibrosis in 9, Wilson's disease in 5 and
      obstructive cholangiopathy in 2 patients. The remaining 19 were normal. Minor
      complications occurred in 2 patients. CONCLUSION: Transjugular liver biopsy is a
      safe procedure in the trained hands and provides adequate tissue for diagnosis
      when percutaneous liver biopsy is contraindicated.

PMID- 18822622
TI  - Prevention awareness counselling and evaluation (PACE) diabetes project: a mega
      multi-pronged program for diabetes awareness and prevention in South India (PACE-
      5).
AB  - OBJECTIVE: The Prevention Awareness Counselling Evaluation (PACE) Diabetes
      Project is a large scale community based project carried out to increase
      awareness of diabetes and its complications in Chennai city (population: 4.7
      million) through 1) public education 2) media campaigns 3) general practitioner
      training 4) blood sugar screening and 5) community based "real life" prevention
      program METHODS: Education took place in multiple forms and venues over the three
      year period of the PACE project between 2004-2007. With the help of the
      community, awareness programs were conducted at residential sites, worksites,
      places of worship, public places and educational institutions through lectures,
      skits and street plays. Messages were also conveyed through popular local
      television and radio channels and print media. The General Practitioners (GPs)
      program included training in diabetes prevention, treatment and the advantages of
      early detection of complications. Free random capillary blood glucose testing was
      done for individuals who attended the awareness programs using glucose meter.
      RESULTS: Over a three-year period, we conducted 774 education sessions, 675 of
      which were coupled with opportunistic blood glucose screening. A total of 76,645
      individuals underwent blood glucose screening. We also set up 176 "PACE Diabetes
      Education Counters" across Chennai, which were regularly replenished with
      educational materials. In addition, we trained 232 general practitioners in
      diabetology prevention, treatment and screening for complications. Multiple
      television and radio shows were given and messages about diabetes sent as Short
      Message Service (SMS) through mobile phones. Overall, we estimate that we reached
      diabetes prevention messages to nearly two million people in Chennai through the
      PACE Diabetes Project, making it one of the largest diabetes awareness and
      prevention programs ever conducted in India. CONCLUSION: Mass awareness and
      screening programs are feasible and, through community empowerment, can help in
      prevention and control of non-commuincable diseases such as diabetes and its
      complications on a large scale.

PMID- 18822623
TI  - Porphyria cutanea tarda.

PMID- 18822624
TI  - Symmetrical peripheral gangrene.

PMID- 18822625
TI  - Challenges in diabetes care in India: sheer numbers, lack of awareness and
      inadequate control.
AB  - With an estimated 40 million people suffering from the condition, the largest in
      any country in the world, diabetes has become a major health care problem in
      India. Recent epidemiological studies from India point to the great burden due to
      diabetes and its micro and macrovascular complications. This is primarily because
      the status of diabetes control in India is far from ideal. Based on the available
      data, the mean glycated hemoglobin levels are around 9% which is at least 2%
      higher than the goal currently suggested by international bodies. The IMPROVE
      study has helped identify the barriers to good control of diabetes both among
      patients as well as physicians in today's practice. However the recent ACCORD
      study points to the dangers of overaggressive treatment, especially in high risk
      in elderly patients. A balanced approach to improve awareness about diabetes and
      its control both among patients and the medical fraternity is urgent need of the
      hour in India. The associated risks of tight control in high risk groups should
      also be kept in mind.

PMID- 18822626
TI  - Hemophagoctic lymphohistiocytosis--recent concept.
AB  - Hemophagocytic lymphohistiocytosis is a rare condition characterized by highly
      stimulated but inactive immune response. The disease may be inherited or acquired
      due to infections, collagen vascular diseases and malignancies. The pathological
      hallmark of the syndrome is aggressive proliferation of macrophages and
      histiocytes. Decreased NK cell activity results in increased T cell activation
      resulting production of large quantities of interferon gamma (IFN gamma), tumor
      necrosis factor alpha (TNF alpha) and granulocyte macrophage colony stimulating
      factor (GM-CSF). This causes sustained macrophage activation and tissue
      infiltration as well as production of interleukin 1 (IL1) and interleukin 6
      (IL6).The resulting inflammatory reaction causes extensive damage and associated
      symptoms. Patients with HLH commonly present with high fever, anemia and
      splenomegaly. Minimal diagnostic parameters are a complete hemogram, liver
      function test, serum triglycerides and ferritin, coagulation profile including
      fibrinogen and bone marrow aspiration. Two highly sensitive diagnostic marker are
      an increased plasma concentration of the alpha chain of soluble IL2 receptor
      (CD25) and impaired NK cell activity. Hyperinflammation can be treated with
      steroid, Cyclosporine prevents T lymphocytes and immunoglobulin infusion helps to
      control the infection. Etoposide may be life saving specially in case of HLH with
      Ebstein Barr Viruses infection. The Histiocyte Society in 1994 developed a common
      treatment protocol (HLH-94). In January 2004 a revised HLH treatment protocol was
      opened entitled HLH-2004, which is based on HLH-94 with minor modifications.
      There is a high remission rate on the HLH-94 and HLH-2004 treatment protocols.

PMID- 18822627
TI  - Primary amoebic meningoencephalitis due to Naegleria fowleri.
AB  - Primary amoebic meningoencephalitis (PAM) due to Naegleria fowleri was detected
      in a 36-year-old, Indian countryman who had a history of taking bath in the
      village pond. He was admitted in a semi comatosed condition with severe frontal
      headache, neck stiffness, intermittent fever, nausea, vomiting, left hemiparesis
      and seizures. Computerized tomography (CT) scan of brain showed a soft tissue non
      enhancing mass with erosion of sphenoid sinus. However CSF findings showed no
      fungal or bacterial pathogen. Trophozoites of Naegleria fowleri were detected in
      the direct microscopic examination of CSF and these were grown in culture on non
      nutrient agar. The patient was put on amphotericin-B, rifampicin and ceftazidime
      but his condition deteriorated and was taken home by his relatives in a moribund
      condition against medical advice and subsequently died. A literature review of 7
      previous reports of PAM in India is also presented. Four of theses eight cases
      were non lethal. The mean age was 13.06 years with male: female ratio of 7:1.
      History of contact with water was present in four cases. Trophozoites could be
      identified in all 8 cases in this series.

PMID- 18822628
TI  - Myocardial damage in hair dye poisoning--an uncommon presentation.
AB  - A 22-year-old female presented to us after consuming hair dye with features of
      angio-neurotic edema, asphyxia and irregular pulse. Serial ECGs revealed presence
      of ST segment elevation and T wave inversion in anterior chest leads. Strongly
      positive c-troponin-T test further confirmed the myocardial damage. This is a
      rare manifestation of para-phenylene diamine poisoning mentioned in literature.
      Patient also had elevated liver enzymes and oliguria.

PMID- 18822629
TI  - Medical philately (medical theme on stamps).

PMID- 18822630
TI  - Purpura fulminans in a complicated Falciparum malaria.
AB  - A 19-year-old male presented with fever, oliguria and purpuric lesions involving
      both hands. The patient was diagnosed as a case of purpura fulminans with
      disseminated intravascular coagulation due to complicated Falciparum malaria. The
      case is presented to sensitize the physicians to keep malaria as a differential
      in cases of fever with purpura fulminans.

PMID- 18822631
TI  - Fatal cerebral abscess caused by Cladophialophora bantiana.
AB  - Primary cerebral phaeohyphomycosis is caused by pigmented fungi that exhibit
      distinct neurotropism often in immunocompetent individuals. A 20-yr-old male
      presented with multiple brain abscess which was subsequently proven
      microbiologically to be due to Cladophialophora Bantiana. In spite of near total
      excision and appropriate antifungal agents succumbed to his illness. We report
      this case to highlight its rarity and high mortality in an immunocompetent host.
      There is no initial clinical or laboratory feature that makes a preoperative
      diagnosis possible and relies on microbiological confirmation.

PMID- 18822632
TI  - Case of ADEM following Chikungunya fever.

PMID- 18822633
TI  - Interesting case of gastroenteritis with 'shock'.

PMID- 18822634
TI  - Recurrent reversible jaundice, neuropsychiatric manifestations, dementia and
      ataxia as manifestations of vit. B12 deficiency.

PMID- 18822635
TI  - Men who have sex with men: new emerging threat of HIV/AIDS spread in Pakistan.

PMID- 18822636
TI  - The epidemic of injuries in Pakistan--a neglected problem.

PMID- 18822637
TI  - Predictive model of blood transfusion during CABG surgery in Pakistan.
AB  - OBJECTIVE: To determine predictors of need for transfusion of blood and blood
      products and create a clinical predictive model to reduce indiscriminate use of
      blood products during surgery. METHOD: We conducted a retrospective chart review
      of 485 patients who underwent coronary artery bypass surgery from January 2004 to
      December 2004 at a Tertiary Care Hospital in Karachi, Pakistan. Independent
      predictors associated with transfusion were identified and a clinical prediction
      model developed. RESULTS: The transfusion rate was 37.1%. A predictive model was
      created based on the presence of pulmonary disease, diabetes mellitus, low
      ejection fraction and recent/ongoing myocardial infarction. CONCLUSION: The study
      identifies some predictors of need for blood transfusion in patients undergoing
      Coronary Artery Bypass Grafting. However, prospective studies with a larger
      sample of patients are needed to determine other predictors and their
      applicability in patient selection across institutions.

PMID- 18822638
TI  - Correlation of age at menarche and height in Iranian student girls living in
      Gorgan--northeast of Iran.
AB  - OBJECTIVE: To see the association of age at menarche with adult height in girls
      living in Gorgan--North of Iran. METHODS: This study included 100 female
      university students (aged 18-21 years) born between 1985-1988 and 200
      intermediate school students (aged 12-15 years) born between 1992-1994. Age at
      menarche and its association with height were studied. Data was analyzed by SPSS
      v11.5 software. Pearson correlation was used to determine the relation between
      menarcheal age and height. RESULTS: There was a significant difference in the age
      of menarche between intermediate school students (12.20 +/- 1.45 years) and
      university students (13.54 +/- 1.30 years). This decreased by 68.54 days per 1
      year. The significant positive association was between age at menarche and
      height. Height of students with menarche at an earlier age was less (P < 0.05).
      There was no significant difference in menarche age in the different
      socioeconomic classes. CONCLUSION: Girls living in Gorgan--North of Iran acquire
      menarche at an early age. Students with earlier menarche reach a shorter adult
      height.

PMID- 18822639
TI  - Is ascending urethrogram mandatory for all urethral strictures?
AB  - OBJECTIVE: To determine the role of ascending urethrogram in decision making for
      patients with suspected urethral strictures. METHODS: Medical Records were
      reviewed of male patients presenting with lower urinary tract symptoms who were
      subjected to ascending urethrogram and selected cases for cystourethroscopy from
      January 2001 to December 2002. Cystourethroscopy was performed on those patients
      who complied with treatment for urethral stricture or who had persistent low flow
      of urine despite ascending urethrogram reporting no urethral stricture. Data was
      analyzed on SPSS 10.0. Sensitivity, specificity, positive and negative predictive
      values were calculated for ascending urethrogram as a measure to evaluate
      urethral stricture. RESULTS: Ascending urethrogram was done on 92 patients. Of
      whom 55 were reported to have urethral stricture. The mean age of patients was
      42.8 +/- 13.2 years. Of the 92 patients who had ascending urethrogram, 62 were
      subjected to cystourethroscopy proceed optical internal urethrotomy (OIU) in
      cases of stricture. It was that out of 45 reported urethral strictures on
      ascending urethrogram, 5 did not have stricture on cystourethroscopy (P = 0.001).
      Likewise in the same group of 62 patients, 17 patients were reported to have no
      stricture on ascending urethrogram, whereas subsequent cystourethroscopy revealed
      stricture in 4 patients. The calculated sensitivity of ascending urethrogram was
      91% and specificity 72%. The calculated positive and negative predictive values
      were 89% and 76% respectively. CONCLUSION: The study concluded that Ascending
      Urethrogram does not completely rule out urethral stricture (Negative Predictive
      Value 76%). It was also observed that urethral stricture may be non-existent even
      though suggested in Ascending Urethrogram (Positive Predictive Value 89%). With a
      sensitivity of 91% and a low specificity of 72% of the ascending urethrogram for
      diagnosing urethral stricture, it would be advisable to subject the patient to
      cystourethroscopy proceed Optical Internal Urethrotomy in cases of urethral
      stricture. This will save cost, avoid infection reduce risk of radiation and
      contrast related hypersensitivity reaction.

PMID- 18822640
TI  - Factors associated with non-adherence among psychiatric patients at a tertiary
      care hospital, Karachi, Pakistan: a questionnaire based cross-sectional study.
AB  - OBJECTIVE: To elucidate predictors of non-adherence among psychiatric patients
      presenting at a tertiary care hospital of Pakistan, for follow-up with consultant
      psychiatrist. METHODS: A convenient sampleof psychiatric patients from Aga Khan
      University Hospital was enrolled between April and May, 2005. An interviewer
      assisted, standardized questionnaire was used for data collection. Patients with
      cognitive deficit or psychosis and those presenting for the first time were not
      included in the study. RESULTS: Out of 128 patients, those with co-morbidity
      (32.81%) were less adherent than those without comorbidity (p-value:0.002).
      Adherence among depressed was 61.53%; psychotic was 58.82%; bipolar disorder was
      73.91%. Reasons for non-adherence included sedation (30%), medication cost (22%),
      forgot to take medication (36%); and inability of the physicians to explain
      timing and dose (92%) or benefit of medication (76%). CONCLUSIONS: Non-adherence
      is a common and important issue. Treatment cost and co-morbidity should be
      reviewed in order to keep the medication regime affordable and comprehensible.

PMID- 18822641
TI  - Primary drug resistance to antituberculous drugs in NWFP Pakistan.
AB  - OBJECTIVE: To assess the prevalence of Primary drug resistance to Antituberculous
      drugs in NWFP METHOD: A cross-sectional prevalence study was undertaken to
      evaluate the prevalence of drug resistance among new TB patients, using a non
      probability convenience sampling methodology. Sample size was calculated
      according to the population and WHO's estimated incidence of smear positive
      tuberculosis in the province/country. Sputum samples were obtained from 122 newly
      diagnosed patients of pulmonary tuberculosis from centres in Peshawar and
      Abbotabad in NWFP. RESULTS: Sensitivities were performed by proportion method
      which showed the following resistance values in 118 eligible patients: 15 (12.7%)
      samples showed primary resistance to one or more drugs. 8 (6.4%) isolates were
      resistant to a single drug, 2 (1.6%) were resistant to 2 drugs, 4 (3.2%) to 3
      drugs, 1 (0.8%) to 4 drugs while none to all 5 first line agents. Resistance to
      Streptomycin (10 microg/ml) was seen in 7 (5.9%), Isoniazid (1 microg/ml) in 10
      (8.4%), Rifampicin (5 microg/ml) in 3 (2.5%), Ethambutol (10 microg/ml) in 2
      (1.6%) and Pyrazinamide in 6 (5.0%) samples. Primary Multidrug resistance was
      2.5%. CONCLUSION: This study suggests that prevalence of MDR amongst untreated
      patients in NWFP is 2.5%, which is a cause of concern and should be addressed
      through effective TB control programmes with DOTS strategy.

PMID- 18822642
TI  - Frequency and clinical spectrum of rare inherited coagulopathies--a tricenter
      study.
AB  - OBJECTIVE: To determine the frequency of rare inherited coagulopathies at three
      centers of haematology in Karachi and to study the clinical spectrum and
      laboratory data of these coagulopathies. METHODS: This was a descriptive study
      conducted from September 2003 to December 2004 on subjects from Aga Khan
      University Hospital, Husaini Blood Bank and Fatimid Blood Transfusion Centre. All
      the subjects with bleeding tendency without any acquired causes of bleeding were
      selected for further investigation, and were asked relevant questions as present
      in the questionnaire. Screening tests including platelet count, PT, APTT and
      bleeding time were performed on all patients and subsequently, specific tests
      including factor assay, clot solubility test, platelet aggregation and vWFAg were
      performed. RESULTS: In total, 1100 patients were evaluated for bleeding tendency
      at the three centers and 65 patients were diagnosed to have inherited
      coagulopathy other than haemophilia A and B. Out of these 65 patients, 33 (50.7%)
      were males and 32 (49.2%) were females. Rare inherited coagulopathies that were
      found in our population included deficiency of factor VII {n = 21 (32.3%)},
      factor X {n = 17 (26.1%)}, factor XIII {n =14 (21.5%)}, factor V {n = 9 (13.8%)},
      fibrinogen {n = 2 (3%)}, prothrombin {n = 1 (1.5%)} and factor XII {n = 1
      (1.5%)}. CONCLUSION: Inherited coagulopathies other than haemophilia A and B were
      noted in the study population.

PMID- 18822643
TI  - Reducing the rate of primary caesarean sections--an audit.
AB  - OBJECTIVE: To evaluate how the implementation of universally acceptable standards
      affects rates for primary caesarean sections, without compromising maternal or
      foetal safety. METHODS: A complete audit cycle of all the primary caesarean
      sections performed in the maternity unit of Aga Khan University was conducted
      from 1st January to 31st March during years 2003 and 2004. New labour management
      guidelines were implemented after the first audit (appendix). The rates of
      caesarean section, induction of labour, failed induction, and maternal and foetal
      outcomes were compared before and after the implementation of the guidelines.
      RESULTS: Primary emergency caesarean section rate decreased from 16% to 12%. A
      reduction in primary caesarean sections was noted in the induced cases. Practice
      of checking cord blood for foetal pH and maintaining partograms improved
      markedly. There were no significant adverse maternal and perinatal outcomes.
      CONCLUSION: Implementation of standard labour management strategies can reduce
      primary caesarean section rate without compromising maternal and foetal safety.

PMID- 18822644
TI  - Clinical outcomes of sirolimus with eluting stent implantation in coronary artery
      disease.
AB  - OBJECTIVE: To evaluate the immediate post procedure, thirty-days, and six-months
      clinical outcomes of sirolimus-eluting stents (SES) implantation in patients with
      single and multivessel coronary artery disease (CAD). METHODS: A case series of
      all consecutive patients undergoing percutaneous coronary interventions (PCI)
      with SES implantation at Shifa International Hospital, Islamabad, were evaluated
      at early post-procedure, 30-days and six-months clinical follow-up for the
      incidence of major adverse cardiac event (MACE). This included death, nonfatal
      myocardial infarction (MI) and repeat revascularization. RESULTS: Out of 206
      consecutive patients, 324 had SES implanted. Cumulative MACE rate was 2.93% and
      6% at 30-days and six-months follow-ups respectively. Five patients developed ST
      segment elevation MI (STEMI). One patient developed non-STEMI. Emergency Coronary
      Artery Bypass Grafting (CABG) was done in two patients. Repeat (PCI) was carried
      in three (1.46%) patients for acute in-stent thrombosis. Diabetes Mellitus and
      multivessel stenting were found to be the independent predictors for acute in
      stent thrombosis (P-value < 0.02 and 0.05 respectively). CONCLUSION: SES
      implantation in coronary artery disease can be safe and effective MACE at one and
      six months follow-ups.

PMID- 18822645
TI  - Migraine and patent foramen ovale: exploring the association and a possible
      treatment option.
AB  - Migraine is a very common type of headache. With a prevalence of 10-12%, migraine
      ranks 19th among diseases causing worldwide morbidity. Number of studies have
      shown a high prevalence of patent foramen ovale (PFO) in patients with migraine,
      especially migraine with aura. The right to left shunting of blood in a PFO could
      serve as a conduit for chemicals that would exert a trigger effect on hyper
      excitable neurons leading to the development of migraine. Furthermore patients
      with PFO and migraine also show a marked improvement in their symptoms after
      percutaneous closure of the PFO. This review is a close look at this association
      and also explores whether subsequent closure of the shunt can be looked upon as a
      viable treatment option.

PMID- 18822646
TI  - Deliberate self-poisoning: experience at a medical unit.
AB  - To share our experience of managing acute DSP patients, a cross sectional,
      observational study was conducted for one year. Patients with acute DSP, defined
      as "ingestion of a poison or excessive dose of a medicine for self-harm" were
      included. Patient demographics (gender, age, educational, and marital status
      etc), intention, substance used, and outcome were noted. Eighty patients (47
      female, and 33 male) were managed. Mean patient age was 24.35 +/- 7.69 years.
      Most of the patients were educated up to 10th grade, were unmarried, resident of
      urban area, occupation wise household related, and belonged to middle class.
      Majority (55%) of patients wanted to commit suicide. Benzodiazepines (31.3%) and
      organophosphate (OP) compounds (21.3%) were commonly used for DSP. 2.5% (n = 2)
      patients expired. DSP with OP compounds was significantly associated with
      suicidal intention.

PMID- 18822647
TI  - A case of histoplasmosis mimicking tuberculosis.
AB  - Drug resistance to Tuberculosis is an emerging problem but proper exhaustive
      workup needs to be done before confirming the diagnosis. The case of a 5 year old
      male child who presented with low grade fever and lymphadenopathy and was being
      treated with anti TB drugs with no satisfactory response is presented. A detail
      workup including a biopsy gave the diagnosis of histoplasmosis.

PMID- 18822648
TI  - An unusual cause of haemoperitoneum in a child.
AB  - We present a case of haemoperitoneum in a child, who presented with signs of
      acute abdomen with subacute intestinal obstruction. Abdominal paracentesis
      aspirated fresh blood. Ultrasound and CT scan abdomen showed loculated
      haemoperitoneum. A definitive diagnosis could not be made andan exploratory
      laparotomy was undertaken which revealed a large cystic lymphangioma of greater
      omentum with acute massive spontaneous haemorrhage. It was excised in toto along
      with the involved omentum leading to excellent recovery. Abdominal cystic
      lymphangioma first presenting as a spontaneous, life threatening haemorrhage has
      to our knowledge, not been reported before. It may have to be included in the
      differential diagnosis of acute haemoperitoneum.

PMID- 18822649
TI  - Anaesthetic management of patient with Ellis Van Creveld syndrome.
AB  - A known case of Ellis-Van Creveld Syndrome was scheduled for emergency repair of
      obstructed paraumblical hernia. We describe the anaesthetic management of the
      case with special reference to the classic physical and physiological
      manifestations of this syndrome present in our patient.

PMID- 18822650
TI  - Autoerotic asphyxia by hanging.
AB  - A case of sexual asphyxial death by hanging is presented. A 41-year-old man was
      found dead hanging by a towrope. A mirror was placed in front of a table,
      reflecting him in full height. A photograph of a celebrity mannequin was found
      against him. The towrope was arranged for the compression of the neck, and
      controlled voluntarily by a shower apparatus. Autopsy findings revealed an
      ascending ligature mark, 2 cm in width on the neck. Although this is a very
      ancient behaviour, we are presenting a very rare case from Turkey. We aim to
      discuss sexual asphyxiation phenomenon together with the features of the previous
      Turkish cases on the aspect of the forensic viewpoint, as well as the
      similarities and differences between different nations and religious.

PMID- 18822651
TI  - Quest for a 'universal psychiatrist': how long is the journey?

PMID- 18822652
TI  - Awareness of bird flu amongst young college students.
AB  - OBJECTIVE: To assess the awareness among students about the disease, their
      attitude during the outbreak, along with their perceptions about treatment, and
      severity of disease. METHODS: A cross sectional study was conducted among 220
      intermediate students. The data was collected through a self filled questionnaire
      after taking verbal consent. The variables included in this study were age,
      gender and department (medical/non-medical). RESULTS: A total of 220 students
      participated with mean age of 17 +/- 1 year. There were 132 (61%) males and 84
      (39%) females. The students were divided into pre-medical 110 (50%) and non
      premedical 110 (50%). About 211 (96%) students said that they had heard about
      bird flu but only 86 (39%) correctly identified it as a disease of birds and
      humans both. One hundred and fifty-four (70%) participants said that virus causes
      it and the most common source of knowledge was media (T.V) by 153 (70%) followed
      by newspaper 113 (51%) respondents. Flu like symptoms were identified by 77 (35%)
      and 160 (73%) considered birds to human as the most likely route of transmission.
      Regarding vaccine, 133 (70%) replied that it is not available and 80 (41%) said
      that there is a treatment for the disease. About 143 (73%) thought that it is
      life-threatening. According to 105 (48%) the suitable preventive measure taken by
      the government would be to kill susceptible chickens. CONCLUSION: The awareness
      regarding bird flu was quite low among students. As bird flu is a world wide
      public health problem therefore increasing awareness would be a solution to avoid
      its spread and complications.

PMID- 18822653
TI  - Polio eradication: an elusive dream?

PMID- 18822654
TI  - Indoor air pollution: an avoidable health risk factor.

PMID- 18822655
TI  - Global research collaboration for priority setting in health systems in
      developing countries.

PMID- 18822656
TI  - Risk factors of cardiovascular disease among the oral contraceptive users in
      Kermanshah City of Iran.

PMID- 18822657
TI  - Will discouraging migration really make doctors happier?

PMID- 18822658
TI  - The nature and context of exploratory experimentation: an introduction to three
      case studies of exploratory research.
AB  - My aim in this article is to introduce readers to the topic of exploratory
      experimentation and briefly explain how the three articles that follow, by
      Richard Burian, Kevin Elliott, and Maureen O'Malley, advance our understanding of
      the nature and significance of exploratory research. I suggest that the
      distinction between exploratory and theory-driven experimentation is
      multidimensional and that some of the dimensions are continuums. I point out that
      exploratory experiments are typically theory-informed even if they are not theory
      driven. I also distinguish between research programs and experiments. Research
      programs that are largely exploratory, such as the ones discussed in these case
      studies, can involve both exploratory and theory-driven experimentation.

PMID- 18822659
TI  - On microRNA and the need for exploratory experimentation in post-genomic
      molecular biology.
AB  - This paper is devoted to an examination of the discovery, characterization, and
      analysis of the functions of microRNAs, which also serves as a vehicle for
      demonstrating the importance of exploratory experimentation in current (post
      genomic) molecular biology. The material on microRNAs is important in its own
      right: it provides important insight into the extreme complexity of regulatory
      networks involving components made of DNA, RNA, and protein. These networks play
      a central role in regulating development of multicellular organisms and
      illustrate the importance of epigenetic as well as genetic systems in evolution
      and development. The examination of these matters yields principled arguments for
      the historicity of the functions of key biological molecules and for the
      indispensability of exploratory experimentation in contemporary molecular biology
      as well as some insight into the complex interplay between exploratory
      experimentation and hypothesis-driven science. This latter result is not only
      important for philosophy of science, but also of practical importance for the
      evaluation of grant proposals, although the elaboration of this latter claim must
      be left for another occasion.

PMID- 18822660
TI  - Varieties of exploratory experimentation in nanotoxicology.
AB  - There has been relatively little effort to provide a systematic overview of
      different forms of exploratory experimentation (EE). The present paper examines
      the growing subdiscipline of nanotoxicology and suggests that it illustrates at
      least four ways that researchers can engage in EE: searching for regularities;
      developing new techniques, simulation models, and instrumentation; collecting and
      analyzing large swaths of data using new experimental strategies (e.g., computer
      based simulation and "high-throughput" instrumentation); and structuring an
      entire disciplinary field around exploratory research agendas. In order to
      distinguish these and other activities more effectively, the paper proposes a
      taxonomy that includes three dimensions along which types of EE vary: (1) the aim
      of the experimental activity, (2) the role of theory in the activity, and (3) the
      methods or strategies employed for varying experimental parameters.

PMID- 18822661
TI  - Exploratory experimentation and scientific practice: metagenomics and the
      proteorhodopsin case.
AB  - Exploratory experimentation and high-throughput molecular biology appear to have
      considerable affinity for each other. Included in the latter category is
      metagenomics, which is the DNA-based study of diverse microbial communities from
      a vast range of non-laboratory environments. Metagenomics has already made
      numerous discoveries and these have led to reinterpretations of fundamental
      concepts of microbial organization, evolution, and ecology. The most outstanding
      success story of metagenomics to date involves the discovery of a rhodopsin gene,
      named proteorhodopsin, in marine bacteria that were never suspected to have any
      photobiological capacities. A discussion of this finding and its detailed
      investigation illuminates the relationship between exploratory experimentation
      and metagenomics. Specifically, the proteorhodopsin story indicates that a
      dichotomous interpretation of theory-driven and exploratory experimentation is
      insufficient and that an interactive understanding of these two types of
      experimentation can be usefully supplemented by another category, "natural
      history experimentation". Further reflection on the context of metagenomics
      suggests the necessity of thinking more historically about exploratory and other
      forms of experimentation.

PMID- 18822662
TI  - Biology and war--American biology and international science.
AB  - The German-born American scientist Jacques Loeb (1859-1924) was one of the most
      important promoters of experimental biology around 1900. He was best known for
      his physico-chemical explanations of psychological processes and his
      biotechnological approach to artificial parthenogenesis. At the start of the
      First World War, Loeb was deeply troubled by the deterioration of the
      international scientific community and the growing alienation of his German and
      American colleagues. The aim of this paper is to examine Jacques Loeb's
      activities aimed at advancing scientific internationalism before, during, and
      after the war. Loeb, for example, tried to negotiate the publication of German
      authors in American journals during the war, at a time when this was
      categorically rejected by publishers. Immediately after the war, he tried to
      create a specific system aimed at disseminating scientific literature and funding
      selected European colleagues, in order to overcome what he considered reactionary
      and hegemonic forces within German scientific institutions. His correspondence
      with eminent scientists from all over the world (amongst them Albert Einstein,
      Richard Goldschmidt, Otto Meyerhof, Otto Warburg, Paul Ehrlich, Wolfgang Ostwald,
      Wilhelm Roux, and Ross Harrison) will serve as a source for the analysis. Special
      emphasis will be placed on the question how Jacques Loeb integrated epistemology,
      his particular world view, and his social commitment into the workings of his own
      life and how he tried to extend his scientific goal of controlling biological
      systems to the sphere of international science.

PMID- 18822663
TI  - Racial classification in the evolutionary sciences: a comparative analysis.
AB  - Human racial classification has long been a problem for the discipline of
      anthropology, but much of the criticism of the race concept has focused on its
      social and political connotations. The central argument of this paper is that
      race is not a specifically human problem, but one that exists in evolutionary
      thought in general. This paper looks at various disciplinary approaches to racial
      or subspecies classification, extending its focus beyond the anthropological race
      concept by providing a comparative analysis of the use of racial classification
      in evolutionary biology, genetics, and anthropology.

PMID- 18822664
TI  - What is marine biology?: Defining a science in the United States in the mid 20th
      century.
AB  - Marine biology and biological oceanography are two disciplinary subfields that
      have long struggled with their definitions. Should marine biology simply be
      considered a part of biology that takes place in the marine environment or is it
      a distinct entity, with conceptual problems and methodological approaches all its
      own? Similarly, biological oceanography could be seen as a necessary adjunct to
      physical and chemical oceanography or it could be defined more as an extension of
      biology into the marine realm. In the United States, these issues were directly
      addressed from the mid 1950s through the mid 1960s in a series of events that
      shed light on how marine biologists came to a working definition of their field
      that provided a broad methodological tent for practitioners and, at the same
      time, allied the field to oceanography during a period in which exploration of
      uncharted areas drew considerable funding from the post-WWII federal agencies
      charged with keeping American science at the forefront.

PMID- 18822665
TI  - Population regulation and the life history studies of LaMont Cole.
AB  - Transformative changes marked the growth of mid-twentieth century American
      ecology. This included redirection of the scholarly focus of the discipline,
      especially on the role evolutionary theory and "levels of selection", and
      increased visibility of ecologist as public figures in the environmental movement
      with special knowledge of how natural systems work. Cornell ecologist LaMont Cole
      is an important figure to examine both of these trends. Like many of his
      contemporaries, Cole was devoted to a perspective on natural selection operating
      at levels above the individual. However, because of his influential mathematical
      treatment of animal demography he has been historically subsumed into a group of
      scholars that views the events in the life course as adaptations to the
      maximization of individual fitness--life history theory. Cole's popular writings
      and lectures, which consumed his later career, extend his scholarly portrayal of
      natural populations as tending toward stable and homoeostatic equilibrium, with
      the goal of drawing contrasts with the deviance of rapid human population growth.
      In both regards, Cole serves as a topical and temporal extension of the well
      documented and analyzed ecology of his mentors--Alfred Emerson, Thomas Park, and
      Warder Allee--in the University of Chicago Zoology Department.

PMID- 18822666
TI  - The circle of nursing knowledge: education, practice, and research. Foreword.

PMID- 18822667
TI  - Knowledge that matters: integrating research, practice, and education.

PMID- 18822668
TI  - Health care transitions of youth with special health care needs: the never ending
      journey.

PMID- 18822669
TI  - Advances in nursing education: virtual experiential communities.

PMID- 18822670
TI  - Thoughts about the state of the science related to culturally competent care for
      persons with chronic illness and its relationship to practice.
AB  - In 1985, a very important event, the distribution of the Heckler Report, changed
      the direction of health policy and health research policy in this country.
      Although we have yet to see a yield of information that is substantially making a
      difference in health disparities, progress is being made and nurse scientists are
      at the forefront of the effort. For example, on December 21, 2001, NINR released
      a request for applications calling for proposals for Partnership Centers on
      Health Disparities (RFA-NR-02-004). The NINR in collaboration with the National
      Center on Minority Health and Health Disparities now funds 11 such Centers. These
      centers are charged with "(1) expanding the cadre of nurse researchers involved
      in minority health or health disparities research, (2) increasing the number of
      research projects aimed at eliminating health disparities, and (3) enhancing the
      career development of potential minority nurse investigators." NINR also
      currently funds seven Institutional National Research Service Awards focused on
      educating young nurse scientists in the conduct of health disparities research.
      So while I'm a little impatient about the progress we've made, I believe that, if
      we keep sight on what nursing research is about and the pressing need to focus
      attention on answering clinical questions about the prevention and treatment of
      chronic conditions, we are well positioned to make an enormous difference in the
      future. Personally, I can't wait to see what's going to happen next.

PMID- 18822671
TI  - One successful nursing research career: the 5 P's and more.

PMID- 18822672
TI  - Longing for everydayness: life after traumatic brain injury in children.

PMID- 18822673
TI  - It's time to make management a true profession.
AB  - In the face of the recent institutional breakdown of trust in business, managers
      are losing legitimacy. To regain public trust, management needs to become a true
      profession in much the way medicine and law have, argue Khurana and Nohria of
      Harvard Business School. True professions have codes, and the meaning and
      consequences of those codes are taught as part of the formal education required
      of their members. Through these codes, professional institutions forge an
      implicit social contract with society: Trust us to control and exercise
      jurisdiction over an important occupational category, and, in return, we will
      ensurethat the members of our profession are worthy of your trust--that they will
      not only be competent to perform the tasks entrusted to them, but that they will
      also conduct themselves with high standardsand great integrity. The authors
      believe that enforcing educational standards and a code of ethics is unlikely to
      choke entrepreneurial creativity. Indeed, if the field of medicine is any
      indication, a code may even stimulate creativity. The main challenge in writing a
      code lies in reaching a broad consensus on the aims and social purpose of
      management. There are two deeply divided schools of thought. One school argues
      that management's aim should simply be to maximize shareholder wealth; the other
      argues that management's purpose is to balance the claims of all the firm's
      stakeholders. Any code will have to steer a middle course in order to accommodate
      both the value-creating impetus of the shareholder value concept and the
      accountability inherent in the stakeholder approach.

PMID- 18822674
TI  - Creativity and the role of the leader.
AB  - In today's innovation-driven economy, understanding how to generate great ideas
      has become an urgent managerial priority. Suddenly, the spotlight has turned on
      the academics who've studied creativity for decades. How relevant is their
      research to the practical challenges leaders face? To connect theory and
      practice, Harvard Business School professors Amabile and Khaire convened a two
      day colloquium of leading creativity scholars and executives from companies such
      as Google, IDEO, Novartis, Intuit, and E Ink. In this article, the authors
      present highlights of the research presented and the discussion of its
      implications. At the event, a new leadership agenda began to take shape, one
      rooted in the awareness that you can't manage creativity--you can only manage for
      creativity. A number of themes emerged: The leader's job is not to be the source
      of ideas but to encourage and champion ideas. Leaders must tap the imagination of
      employees at all ranks and ask inspiring questions. They also need to help their
      organizations incorporate diverse perspectives, which spur creative insights, and
      facilitate creative collaboration by, for instance, harnessing new technologies.
      The participants shared tactics for enabling discoveries, as well as thoughts on
      how to bring process to bear on creativity without straitjacketing it. They
      pointed out that process management isn't appropriate in all stages of creative
      work; leaders should apply it thoughtfully and manage the handoff from idea
      generators to commercializers deftly. The discussion also examined the need to
      clear paths through bureaucracy, weed out weak ideas, and maximize the
      organization's learning from failure. Though points of view varied, the theories
      and frameworks explored advance the understanding of creativity in business and
      offer executives a playbook for increasing innovation.

PMID- 18822675
TI  - What was privacy?
AB  - Why is that question in the past tense? Because individuals can no longer feel
      confident that the details of their lives--from identifying numbers to cultural
      preferences--will be treated with discretion rather than exploited. Even as
      Facebook users happily share the names of their favorite books, movies, songs,
      and brands, they often regard marketers' use of that information as an invasion
      of privacy. In this wide-ranging essay, McCreary, a senior editor at HBR,
      examines numerous facets of the privacy issue, from Google searches, public
      shaming on the internet, and cell phone etiquette to passenger screening devices,
      public surveillance cameras, and corporate chief privacy officers. He notes that
      IBM has been a leader on privacy; its policy forswearing the use of employees'
      genetic information in hiring and benefits decisions predated the federal Genetic
      Information Nondiscrimination Act by three years. Now IBM is involved in an open
      source project known as Higgins to provide users with transportable, potentially
      anonymous online presences. Craigslist, whose CEO calls it "as close to 100% user
      driven as you can get," has taken an extremely conservative position on privacy-
      perhaps easier for a company with a declared lack of interest in maximizing
      revenue. But TJX and other corporate victims of security breaches have discovered
      that retaining consumers' transaction information can be both costly and risky.
      Companies that underestimate the importance of privacy to their customers or fail
      to protect it may eventually face harsh regulation, reputational damage, or both.
      The best thing they can do, says the author, is negotiate directly with those
      customers over where to draw the line.

PMID- 18822676
TI  - Clinical update on palonosetron in the management of chemotherapy-induced nausea
      and vomiting.
AB  - The need to control chemotherapy-induced nausea and vomiting is continuously
      stimulating research to find better options for the optimal antiemetic care.
      Palonosetron is different from conventional serotonin receptor antagonists not
      only by the fact of having a longer half-life but also by higher binding affinity
      for serotonin receptors. It is the first agent in the class which is approved for
      preventing both delayed and acute emesis induced by moderately emetogenic
      chemotherapy. Recent studies using palonosetron-based antiemetic regimens, as
      well as in the clinical setting of multiple-day chemotherapy, have been reported.
      Palonosetron plus dexamethasone given as a pre-treatment infusion was effective
      for preventing acute and delayed emesis after moderately emetogenic chemotherapy.
      Palonosetron in combination with dexamethasone and aprepitant was highly
      effective in preventing emesis in the days following administration of moderately
      emetogenic chemotherapy. Treatment was well tolerated, with no unexpected adverse
      events. Multiple-day dosing of palonosetron plus dexamethasone was safe and
      effective for prevention of emesis induced by 5-day cisplatin-based chemotherapy.
      There was no evidence of cumulative toxicity when palonosetron was given three
      times over 5 days. Further evidence from ongoing clinical trials with
      palonosetron with or without dexamethasone will be available soon. Palonosetron
      represents an useful addition to the therapeutic armamentarium for the management
      of chemotherapy-induced nausea and vomiting. Further studies are needed to assess
      the effectiveness of palonosetron in combination with dexamethasone compared with
      that of older serotonin receptor antagonists combined with dexamethasone.
      However, palonosetron may offer advantages of convenience over the short-acting
      older antagonists due to its ability to be given as a single intravenous dose
      prior to chemotherapy.

PMID- 18822677
TI  - Radiochemotherapy with cisplatin and oral tegafur in advanced head and neck
      cancer: long-term results of a phase II study.
AB  - AIMS AND BACKGROUND: To evaluate the tolerance and efficacy of an original
      concurrent radiochemotherapy regimen in locally advanced head and neck cancer.
      METHODS: Sixty-four patients with stage III or IV squamous cell carcinoma arising
      from a head and neck mucosal site were eligible. Simultaneous radiochemotherapy
      consisted of two courses of continuous infusional cisplatin (20 mg/m2/d, days 1-4
      and 29-32) and oral tegafur (1200 mg/d, days 1-14 and 29-43), together with
      conventional radiation therapy up to a total dose of 70-75 Gy over nine weeks.
      RESULTS: All the patients were evaluated for toxicity and response. Acute
      mucositis was the most prevalent complication. Grade 3 toxicities were mucositis
      (44%), skin toxicity (10%), leukopenia (8%), and thrombocytopenia (1%). No toxic
      death was observed. Complete response to treatment was observed in 72% of
      patients. With a median follow-up of 48.5 months (range, 27-84), 5-year actuarial
      rate of local-regional control, disease-free survival, overall survival and
      disease-specific survival were 60% (95% confidence interval [CI], 40-70%), 55%
      (95% CI, 45-65%), 51% (95% CI, 43-59%) and 61% (95% CI, 53-69%), respectively.
      CONCLUSIONS: Response, local-regional control and survival rates are equivalent
      to those reported from other concomitant radiochemotherapy combinations. However,
      the regimen offers the advantage of its tolerance and toxicity profile.

PMID- 18822678
TI  - Stromal tumors of the stomach: a clinicopathological study of 15 cases and review
      of the literature.
AB  - AIMS AND BACKGROUND: Gastrointestinal stromal tumors are the most common
      mesenchymal tumors of the digestive tract, although their incidence is low. These
      tumors make up a unique entity based on their molecular pathogenesis,
      immunohistochemical staining and responsiveness to targeted therapy.
      Gastrointestinal stromal tumors vary in malignant potential ranging from small
      incidentally detected tumors with an excellent outcome to aggressive sarcomas.
      Their optimal diagnostic approach and treatment remain a matter of debate. We
      present our experience in this rapidly moving field. METHODS: We present our
      experience on 15 patients presented during a 5-year period (June 2000-September
      2005) with gastrointestinal stromal tumors located in the stomach. RESULTS: Upper
      gastrointestinal endoscopy and CT scan revealed the tumors in all cases. All
      patients underwent curative surgery. A definitive diagnosis was established after
      surgery. CONCLUSIONS: Although an inverse correlation between level of risk and
      survival of patients with gastrointestinal stromal tumors has been observed, 6 of
      our patients with an intermediate risk of recurrence had a favorable outcome.

PMID- 18822679
TI  - Trastuzumab and vinorelbine as highly effective and safe therapy for HER-2
      overexpressing metastatic breast cancer. A single institution experience.
AB  - AIMS AND BACKGROUND: Trastuzumab-based therapy has improved survival of women
      with human epidermal growth factor receptor 2 (HER2)-overexpressing metastatic
      breast cancer. STUDY DESIGN: From September 2002 to July 2006, 45 women with
      metastatic breast cancer HER2 3+, or 2+ and positive for HER2 gene amplification,
      were enrolled in the study and received a combination therapy with vinorelbine,
      25 mg/m2 weeks 1 and 2, plus trastuzumab, 4 mg/kg loading dose and then 2 mg/kg
      weekly, in a three weeks cycle. Eligibility criteria included measurable disease
      and a baseline ejection fraction > or = 50%. Forty-two percent of the patients
      were not pretreated, whereas 58% had received a previous chemotherapy regimen for
      metastatic disease, including anthracyclines and/or taxanes (47%), and
      trastuzumab plus taxol (11%). RESULTS: We observed 14 (31%) complete responses
      and 21 (47%) partial responses, with an overall response rate of 78%. Stable
      disease > 6 months was assessed for 5 (11%) patients with a clinical benefit of
      89%. Five (11%) patients progressed. With a median follow-up of 11 months, median
      time to progression was 9 months and median duration of response was 7.6 months
      for complete remissions and 4 months for partial remissions. Median survival was
      29 months. CONCLUSIONS: In spite of a smaller dose intensity of vinorelbine than
      previously reported, the regimen evaluated was notably effective in terms of
      response rate, time to progression and survival, with very mild toxicity.

PMID- 18822680
TI  - Adjuvant chemotherapy and whole abdominal irradiation for gastric carcinoma.
AB  - AIMS AND BACKGROUND: To analyze the efficacy and toxicity of adjuvant
      chemotherapy followed by whole abdominal irradiation in the treatment of
      resectable gastric cancer with positive lymph nodes. METHODS AND STUDY DESIGN:
      Between 1996 and 1999, 10 patients with node-positive gastric cancer underwent
      complete gross resection and were treated by postoperative chemoradiotherapy. The
      chemotherapy regimen consisted of 5-fluorouracil, 1000 mg/m2/day as a 96-hr
      continuous infusion on day 1, and cisplatin, 100 mg/m2 on day 2, every 21 days.
      Six courses were planned. Radiotherapy was administered 3 weeks after completion
      of the chemotherapy protocol as a single-fraction dose of 600 cGy in a two-field
      (anterior and posterior) configuration. RESULTS: Treatment was generally well
      tolerated, with no treatment-related deaths. However, 9 of the 10 patients died
      of recurrent disease, with a median survival of 20 months (range, 7-84).
      CONCLUSIONS: Adjuvant chemotherapy with whole abdominal irradiation for gastric
      cancer is safe and tolerable but has no apparent effect on patient outcome.
      Studies in larger series are needed to evaluate the role of the approach in this
      disease.

PMID- 18822681
TI  - Gemcitabine and cisplatin treatment of advanced-stage non-small-cell lung cancer
      in patients given cisplatin on day 8.
AB  - AIMS AND BACKGROUND: Gemcitabine and cisplatin treatment were administered to
      patients with advanced-stage, non-small-cell lung cancer. During phase II
      studies, the treatment is performed using a 28-day cycle, with gemcitabine
      administered on days 1, 8, and 15. Although it is advised that cisplatin not be
      administered on the first day, gemcitabine and cisplatin treatment is usually
      performed using a 21-day cycle, with gemcitabine administered on days 1 and 8,
      and cisplatin is given on the first day in most phase III studies. In contrast
      with previous phase III studies, cisplatin was administered on day 8 in our
      study. Dose density, drug toxicity, and efficacy were analyzed. METHODS AND STUDY
      DESIGN: Chemonaive patients with stage IIIB or stage IV nonsmall-cell lung cancer
      received gemcitabine (1250 mg/m2) on days 1 and 8 plus cisplatin (75 mg/m2) on
      day 8 every 3 weeks (1 cycle contained 2 applications). RESULTS: Sixty-seven
      patients received a total of 293 applications. Dose densities were 92.3% for
      gemcitabine and 93.9% for cisplatin. The types and rates of grade 3 and grade 4
      hematologic toxicities were anemia (6%), granulocytopenia (46%), and
      thrombocytopenia (6%). Complete remission was seen in 2 patients (3%); partial
      remission was 40%, stable disease was 39%, and progression of disease, 10%. The
      median overall survival time was 13 months. The median progression-free survival
      time was 9.5 months. One-year survival rate was 54% and 2-year survival, 10.4%.
      CONCLUSIONS: In this 21-day treatment regimen, overall survival was longer than 1
      year and the 1-year survival rate was more than 50%. Both the severity and rate
      of observed thrombocytopenia in the study were very low. Other adverse effects in
      the current study were comparable to those reported in the literature.

PMID- 18822682
TI  - Correlation between magnetic resonance imaging and histopathological tumor
      response after neoadjuvant chemotherapy in breast cancer.
AB  - AIM: To evaluate the accuracy of magnetic resonance imaging in assessing tumor
      response following neoadjuvant chemotherapy in patients with locally advanced
      breast cancer. MATERIALS AND METHODS: Twenty-six patients entered a phase II
      study of neoadjuvant chemotherapy, undergoing bilateral breast magnetic resonance
      imaging before therapy and before surgery. Tumor response was classified using
      RECIST criteria, using tumor size at magnetic resonance imaging. The latter was
      then compared to residue found at histopathological examination. RESULTS:
      Magnetic resonance imaging showed 6 (23%) complete responses, 17 (65%) partial
      responses, 3 (11.5%) disease stabilizations and no disease progressions. Twenty
      three tumors (88.5%) were considered responsive and 3 (11.5%) unresponsive.
      Pathological tumor response was: 6 complete responses (23%), 17 partial responses
      (65%), 2 stable disease (8%), 1 progression (4%). When results of the
      preoperative magnetic resonance imaging were compared to pathological tumor
      response, magnetic resonance imaging overestimated tumor size in 12 cases (46%)
      and underestimated it in 9 (35%). However, preoperative magnetic resonance
      imaging failed to detect invasive tumor in 2 false-negative cases (8%), 1 of
      which was multifocal. Mastectomy was performed in 12 cases: 1 case of disease
      progression even though the neoplasm appeared smaller at magnetic resonance
      imaging, 3 cases with stable disease, and 4 cases with T3 or T4 disease. The 9th
      patient was T2N2 with initial retroareolar disease and negative magnetic
      resonance imaging after chemotherapy. The 10th patient, affected by lobular
      cancer, was in partial remission but was T3N1. The 11th patient was 57 years old
      but was not interested in conservative surgery. The 12th patient requested
      bilateral prophylactic mastectomy due to her positive family history of breast
      cancer. CONCLUSIONS: Magnetic resonance imaging of the breast allowed
      conservative surgery in 54% of the patients. This low value is primarily due to
      overestimation of tumor size, with a negative predictive value of 67% in our
      population. However, surgeons were able to choose conservative surgery with
      relative safety in cases of small residual disease.

PMID- 18822683
TI  - Complete response of colorectal liver metastases after intra-arterial
      chemotherapy.
AB  - AIMS AND BACKGROUND: We demonstrated that colorectal liver metastases considered
      in complete response after intra-arterial floxuridine-based chemotherapy had
      recurred in situ. METHODS AND STUDY DESIGN: One hundred and six colorectal liver
      metastases disappeared after intra-arterial chemotherapy. Persistent macroscopic
      disease was observed at surgery at the site of 52 of 106 liver metastases, even
      though computerized tomography scan and ultrasound showed a complete response.
      The sites of 35 initial liver metastases that were not visible at surgery were
      resected. Pathologic examination of these sites, considered in complete response,
      showed viable cancer cells in 22 of 35 cases. RESULTS: After 1 year of follow-up,
      33 of 106 liver metastases considered in complete response had recurred in situ.
      After 2 years of follow-up, persistent macroscopic or microscopic residual
      disease or recurrence was observed in 86 (81%) of the 106 liver metastases.
      CONCLUSIONS: Nevertheless, 19% of the patients had a long-lasting response. This
      means that floxuridine given as intra-arterial hepatic chemotherapy can still be
      considered an interesting option of cure in the treatment of colorectal liver
      metastases. When feasible, the site of the lesion that disappeared after intra
      arterial chemotherapy should be resected at surgery. The best palliative cure of
      liver metastases should be the combination of local-regional strategies like
      intra-arterial chemotherapy, surgery or radiofrequency ablation with the systemic
      approach.

PMID- 18822684
TI  - Gliosarcomas in the elderly: analysis of 7 cases and clinico-pathological
      remarks.
AB  - AIMS AND BACKGROUND: Gliosarcomas are rare malignant primary brain tumors that
      usually affect the fifth or sixth decades of life. The purpose of this study was
      to describe our experience with such lesions in elderly patients and to establish
      their prognosis factors. METHODS: Between 1993 and 2001, 7 patients over 60 years
      of age were treated at our institute for cerebral gliosarcomas. All patients
      underwent surgery for total or at least sub-total removal of a neoplastic mass.
      RESULTS: Owing to poor clinical conditions (Karnofsky performance score = 40),
      one patient was not treated postoperatively. Remaining patients were treated with
      whole-brain radiotherapy, whereas concomitant chemotherapy (temozolomide) was
      administrated only to 4 patients. Histological examination showed the prevalence
      of sarcomatous aspects in 3 patients; the gliomatous aspect prevailed in 4
      patients. CONCLUSIONS: Sarcomatous aspects and multimodality treatment (surgery,
      radiotherapy and chemotherapy) were associated with a better prognosis and showed
      in these elderly patients a trend similar to that of young people.

PMID- 18822685
TI  - Retroperitoneal soft tissue sarcoma: prognostic factors and therapeutic
      approaches.
AB  - AIMS AND BACKGROUND: Retroperitoneal sarcomas are a rare group of malignant soft
      tissue tumors with a generally poor prognosis. The aim of the study was to assess
      clinical, pathological and treatment-related factors affecting prognosis in
      patients with retroperitoneal sarcomas. METHODS AND STUDY DESIGN: The hospital
      records of 73 patients who underwent surgical exploration at our unit for primary
      retroperitoneal sarcomas between 1984 and 2003 were reviewed. Factors influencing
      overall and disease-free survival were analyzed for all patients and for those
      who underwent complete surgical resection. RESULTS: The complete resectability
      rate was 69.8% (51/73). Operative mortality and morbidity rates were 2.7% and
      21.9%, respectively. For patients who underwent complete resection, the 5-year
      survival rate was 58.3%, whereas it was 0% in cases of incomplete or no resection
      (P < 0.001). Local recurrence rate was 37.2%. Incomplete gross surgical resection
      and microscopic infiltration of margins were the most important independent
      predictors of a poor prognosis. CONCLUSIONS: The present study confirmed the
      importance of an aggressive surgical management for retroperitoneal sarcomas to
      offer these patients the best chance for long-term survival.

PMID- 18822686
TI  - Cell invasiveness in sarcomas: a possibly useful clinical correlation.
AB  - AIMS AND BACKGROUND: The prognosis of each individual patient affected by
      sarcoma, including those with low histopathologic grading, cannot be reliably
      predicted at the time of surgery. We have developed an in vitro cell invasion
      assay on early primary cell cultures derived from surgically removed sarcomas.
      METHODS: Primary cell cultures were subjected to in vitro cell invasion assays by
      using Boyden chambers, filters coated with matrigel and fetal bovine serum as a
      source of chemoattractant. For each primary cell culture, the sarcoma cell
      invasion index was determined in comparison with the percentage of human
      fibrosarcoma HT1080 cell invasion extent. The cell invasion index of 7 different
      sarcomas was evaluated in respect to the outcome of the disease, after a follow
      up ranging from 14 to 48 months. RESULTS: Data evidenced that a low cell invasion
      index (39.7% +/- 8.9) was retained by tumor cells derived from patients with no
      progression of the disease and with a longer interval of disease-free survival
      (21 +/- 0.8 months). However, an increase in cell invasion index (61% +/- 5) was
      retained by tumor cells derived from patients with progression of the disease and
      with a shorter disease-free survival (9 +/- 3 months). Overall, although only 7
      cases were analyzed, a statistically significant correlation was found between
      disease-free survival and cell invasion index (P = 0.003). CONCLUSIONS: Our data
      support the possibility that cell invasion assays performed in vitro on cells
      derived from human sarcomas may be predictive of a more aggressive form of the
      disease.

PMID- 18822687
TI  - Serum IL-6, IL-8, IL-10 and beta2-microglobulin in association with International
      Prognostic Index in diffuse large B cell lymphoma.
AB  - AIMS AND BACKGROUND: Diffuse large B-cell lymphoma displays striking
      heterogeneity at clinical, genetic and molecular levels. The International
      Prognostic Index is useful to predict the outcome of diffuse large B-cell
      lymphoma patients. However, patients with identical International Prognostic
      Index values in clinical practice exhibit marked variability in survival,
      suggesting the presence of significant residual heterogeneity within each
      category. Since cytokines such as interleukin-6, -8 and -10 play important roles
      in the pathogenesis of lymphomas, and plasma level of beta2-microglobulin is
      associated with the outcome of patients with diffuse large B-cell lymphoma, the
      aim of the present study was to determine whether these parameters combined with
      the International Prognostic Index would better stratify these patients to
      predict their prognosis. PATIENTS AND METHODS: The study included 46 untreated
      diffuse large B-cell lymphoma patients. RESULTS: All study parameters
      (International Prognostic Index, Ann Arbor stage, extranodal involvement,
      performance status, lactate dehydrogenase, beta2-microglobulin, interleukin-6 and
      -10, and response to therapy) except for patient age and serum interleukin-8
      level were associated with overall survival. In addition, the International
      Prognostic Index was strongly correlated with beta2-microglobulin, interleukin-6,
      -8 and -10, and when combined these parameters significantly better stratified
      patients according to survival. On multivariate analysis, therapeutic response to
      the primary treatment, elevated interleukin-6 and -10 levels, and the
      International Prognostic Index were significant predictors of overall survival.
      CONCLUSIONS: Our data imply that interleukins and beta2-microglobulin evaluation
      should be used in association with the International Prognostic Index to define
      prognostic subgroups in diffuse large B-cell lymphoma patients.

PMID- 18822688
TI  - PSA use and incidence of prostate biopsy in the Tuscany region: is opportunistic
      screening discounting biopsy in subjects with PSA elevation?
AB  - AIMS AND BACKGROUND: To assess PSA use in the general population and estimate
      biopsy rate subsequent to opportunistic screening. METHODS AND STUDY DESIGN: We
      report on PSA testing and related prostate biopsy frequency in the Tuscany Region
      during 2004-2005 to establish current patterns of care. We used population data
      sources to survey PSA testing and biopsy and estimated expected PSA values and
      expected recommended biopsies (> or = PSA 4 ng/ml) from the ongoing Florence arm
      of the European Study of Screening for Prostate Cancer (ERSPC). RESULTS: PSA
      testing was common for both years and across age groups, increasing with age and
      peaking at 70-74 years (37.6% in 2004, 41.9% in 2005) and increasing over the 2
      years. PSA use in the 55-69 years cohort (screening age in ERSPC) was 28.3% in
      2004 and 30.4% in 2005. Repeat PSA testing was also common and repeat PSA
      probability increased with age, peaking at age 70-74 (60.9%); repeat PSA testing
      at age 55-69 was 53.7%. Overall, 1.3% and 1.2% of men had a biopsy following PSA
      testing in 2004 and 2005. Observed/expected biopsy incidence was 14.3% in 2004
      and 13.2% in 2005. ERSPC compliance to recommended biopsy was 77% or 60% at first
      or repeat screening. CONCLUSIONS: A discordance was identified between high PSA
      testing prevalence and low prostate biopsy rate. Based on projections from the
      ERSPC, this indicates a much lower observed biopsy rate than expected in
      organized screening. Although the implications of this are difficult to quantify
      in the absence of evidence on screening efficacy, it suggests inefficient
      practice.

PMID- 18822689
TI  - Cellular mechanisms of hepatocyte growth factor-mediated urokinase plasminogen
      activator secretion by MAPK signaling in hepatocellular carcinoma.
AB  - AIMS AND BACKGROUND: The hepatocyte growth factor, its receptor c-Met, and
      urokinase-type plasminogen mediate various cellular responses on activation,
      including proliferation, survival, invasion, and metastasis. The regulatory
      mechanisms for the proliferation and the particular invasive phenotypes of
      hepatocellular carcinoma are not yet fully understood. In order to clarify the
      intracellular downstream signal for hepatocyte growth factor/c-Met signaling in
      tumor progression and metastasis in hepatoma, we determined the effects of a
      specific MEK1 inhibitor (PD 098059) and a p38 kinase inhibitor (SB 203580) on
      hepatocyte growth factor-mediated cell proliferation and urokinase-type
      plasminogen expression in hepatoma cell lines (HepG2 and Hep3B). RESULTS:
      Hepatocyte growth factor treatment induced the phosphorylation of ERK and p38
      kinase in a dose-dependent manner, resulting in an early peak of phosphorylation
      at 3 to 10 min, which then rapidly decreased to a near basal level. Pretreatment
      with PD 098059 reduced hepatocyte growth factor-mediated cell proliferation and
      urokinase-type plasminogen secretion. In contrast, SB 203580 pretreatment
      enhanced cell proliferation and urokinase-type plasminogen secretion due to
      induction of ERK phosphorylation. Treatment with PD 098059 and SB 203580 resulted
      in a decrease in phospho-ERK activity. Stable expression of dominant negative
      MEK1 in HepG2 cells showed a decrease in hepatocyte growth factor-mediated
      urokinase-type plasminogen secretion. CONCLUSIONS: Such results suggest that
      interaction of an MEK/ERK and a p38 kinase might be critical in intrahepatic
      invasion and metastasis of human hepatoma cells.

PMID- 18822690
TI  - Clinicopathological significance of overexpression of TSPAN1, Ki67 and CD34 in
      gastric carcinoma.
AB  - To investigate the expression of TSPAN1 (Gene ID: 10103), Ki67 and CD34 in
      gastric carcinomas and the clinicopathological significance, the expression of
      TSPAN1, Ki67 and CD34 was detected in 86 cases of gastric carcinoma, paraffin
      embedded sections using an immunohistochemical method. The rates of
      overexpression of TSPAN1, Ki67 and CD34 in gastric carcinomas were 56.98%,
      74.42%, and 62.79%, respectively. The overexpression of these markers was
      positively correlated with clinical stage and negatively correlated with survival
      rates (at 3 and 5 years). The overexpression of TSPAN1 and Ki67 was negatively
      correlated with carcinoma differentiation, and the overexpression of TSPAN1 and
      CD34 was positively correlated with infiltration and lymph node status of the
      tumor. Thus, overexpression of TSPAN1, Ki67 and CD34 in gastric cancer tissues is
      associated with development of the cancer. The detection of expression of TSPAN1,
      Ki67 and CD34 in gastric cancer may provide useful prognostic information for
      patients with the disease.

PMID- 18822691
TI  - RNA interference-mediated silencing of the Hsp70 gene inhibits human gastric
      cancer cell growth and induces apoptosis in vitro and in vivo.
AB  - AIMS AND BACKGROUND: The role of heat shock protein (HSP) 70 in gastric cancer
      has been extensively examined in many studies for the past decade. It has been
      demonstrated that over-expression of Hsp70 might play important role in malignant
      transformation and maintenance of malignant phenotypes. Therefore, silencing the
      Hsp70 gene could be applicable in molecular therapies of human gastric cancer.
      Herein, we designed a small interfering RNA targeting Hsp70 to knock down its
      expression and investigated its effect on cell proliferation and apoptosis in a
      gastric cancer cell line. METHODS: Two plasmids (phsp1-siRNA, phsp2-siRNA), along
      with a negative control (phsp3-siRNA), were created using a genic recombination
      technique. BGC823 cell lines were used to perform experiments. Western blotting
      and RT-PCR were used to detect Hsp70 expression in vitro and in vivo. Cell
      morphology was observed under light microscope. Cell cycle and apoptosis were
      analyzed by flow cytometry and acridine orange/ethidium bromide double stain, and
      cell proliferative activity was measured by alamarblue assay. In all experiments,
      a negative control served as a baseline measure. RESULTS: We successfully
      constructed phsps-siRNA plasmids and transfected them into BGC823 cells. RT-PCR
      and western blotting revealed that the expression of Hsp70 was down-regulated in
      transfection groups compared with the control group. Flow cytometric analysis
      indicated that less S-phase fraction accumulated in small interfering RNA
      transfected cells than in parental cells and the cells transfected with empty
      vector. CONCLUSIONS: Our results demonstrated that RNAi against Hsp70 could
      effectively knock down gene expression, inhibit growth of cancer cells, induce
      cell cycle arrest and increase cell apoptosis in vitro and in vivo. Hsp70 might
      serve as a therapeutic target for human gastric cancer.

PMID- 18822692
TI  - NF2 expression levels of gastrointestinal stromal tumors: a quantitative real
      time PCR study.
AB  - Gastrointestinal stromal tumors are the most common mesenchymal tumors of the
      gastrointestinal tract. Until today, there have been few markers specific for the
      tumor. This has complicated the differential diagnosis of the neoplasm from
      tumors of smooth muscle origin. Recently, the proto-oncogene c-kit has been shown
      to be a very relevant marker as it almost invariably is expressed in
      gastrointestinal stromal tumors. Radiation exposure, hormonal and genetic
      factors, particularly neurofibromatosis 2, have been implicated in their
      development and growth. GIST initiation, either in NF2-associated or in sporadic
      cases, is linked to inactivation of members of the proteins 4.1 superfamily. The
      majority of the mutations identified in the NF2 gene result in a truncated
      protein and are clinically associated with a severe phenotype. Occasionally,
      missense mutations associated with a mild phenotype may occur. We compared NF2
      gene expression in 5 cases with gastrointestinal stromal tumors by quantitative
      real-time polymerase chain reaction analysis. NF2 gene mRNA expression was
      assessed in fresh tissue of stomach from 5 consecutive patients. We detected no
      alterations in NF2 gene expression in the quantitative analyses of the 5 tumors.

PMID- 18822693
TI  - Significance of p57(Kip2) down-regulation in oncogenesis of bladder carcinoma: an
      immunohistochemical study.
AB  - AIMS AND BACKGROUND: Cyclin-dependent kinase inhibitors have important roles in
      the oncogenesis of various tumors including urothelial cancer. The aim of this
      study was to establish the importance of p57(Kip2), a unique cyclin-dependent
      kinase inhibitor, in the oncogenesis of bladder carcinoma. This article also
      focused on another cyclin-dependent kinase inhibitor, p27(Kip1), and telomerase
      enzyme and examined the relationship between these proteins. MATERIAL AND
      METHODS: Thirty-one patients with urothelial carcinomas of the bladder and 7
      cases with normal urinary bladder mucosa were included in the study.
      Immunohistochemical study was performed by monoclonal antibodies of p27(Kip1),
      p57(Kip2), and the telomerase subunit (hTERT). All immunohistochemical
      preparations were evaluated by an immunohistochemical histological score.
      RESULTS: p57(Kip2) and p27Kip1) expression were seen in all of the cases of
      normal mucosa. In carcinoma cases, 8 of 31 (25.8%) showed p57(Kip2) nuclear
      positivity and 20 of 31 (64.5%) expressed nuclear p27(Kip1). HSCOREs of carcinoma
      cases showed lower scores of nuclear p57(Kip2) and p27(Kip1) than normal mucosa,
      but only HSCOREs of nuclear p57(Kip2) (P = 0.001) showed statistical
      significance. Despite unknown significance, cytoplasmic p57(Kip2) and p27(Kip1)
      were also evaluated. Immunohistochemical analysis showed that carcinomas
      expressed higher HSCOREs of hTERT than normal mucosa, and there was a significant
      difference (P = 0.026) between muscle invasive carcinomas and normal mucosa.
      CONCLUSIONS: The data showed that p57(Kip2) down-regulation along with p27(Kip1)
      is a well-established feature of urothelial carcinoma. Probably, this down
      regulation of cyclin-dependent kinase inhibitors supports the proliferation phase
      of oncogenesis. In the study, we also showed that hTERT expression was up
      regulated in higher stages of urothelial carcinoma.

PMID- 18822694
TI  - 5-HTTLPR polymorphism of serotonin transporter and effects of sertraline in
      terminally ill cancer patients: report of eleven cases.
AB  - Depression is difficult to detect in cancer patients, though its determination
      offers an opportunity to relieve patients' suffering in palliative care.
      Selective serotonin reuptake inhibitors (SSRIs) are the treatment of choice for
      mood disorders, but they show a highly variable response. The short allelic
      variants "s/s" and "s/l" of the 5-HTTLPR polymorphism in the promoter region of
      the serotonin transporter gene has been consistently associated with a poorer
      response to SSRIs. The aim of this study has therefore been to examine
      depression, anxiety and mental adaptation to cancer in terminally ill and
      depressed cancer patients, in relation to treatment with sertraline and to the 5
      HTTLPR genetic polymorphism. Eleven consecutive depressed patients with different
      forms of advanced cancer who were admitted to the Hospice of the Casa di Cura
      "Pineta del Carso" (Trieste, Italy) were treated with sertraline for two weeks
      and their response was determined and related to 5-HTTLPR. Sertraline
      significantly reduced the average depression and anxiety subscale scores of HADS,
      as well as the scores of the subscales of Mini-MAC. When the effects of
      sertraline were analyzed in relation to the 5-HTTLPR polymorphism, only patients
      with the "l/l" allelic variant had significantly lower scores of HADS anxiety,
      Mini-MAC hopelessness-helplessness and anxious preoccupation, and a higher score
      for the fighting spirit of Mini-MAC; the depression score was significantly
      reduced in patients with both allelic variants. These data indicate that
      sertraline is effective after two weeks of treatment in terminally ill cancer
      patients, acting not only on depression but also on anxiety and mental adaptation
      to cancer. Moreover, the effect of sertraline significantly depended on the
      genetic polymorphism of the serotonin transporter, being more pronounced in
      patients carrying the "l/l" genetic variant; these findings seem to encourage the
      examination of a larger sample of patients.

PMID- 18822695
TI  - Psychological assessment of women on an early breast screening program after
      radiotherapy to the chest wall for childhood cancer.
AB  - AIMS AND BACKGROUND: This study investigates the psychological status in a
      population of female patients who received chest irradiation for a childhood
      cancer and were screened for second primary breast cancer. METHODS: Sixty-eight
      consecutive such young women were included. Compilation of the Crown-Crisp Index
      questionnaire was requested and 49/68 patients accepted to fill it in; 14 women
      in the sample had children (28%). RESULTS: Twenty-seven of 49 patients achieved a
      normal score, whereas in 22 the score was slightly above the normal range in at
      least one scale. Pathological scores were more frequent among the women without
      children. CONCLUSION: Quality of life in this series of long-term survivors does
      not seem to be severely affected by previous treatment for cancer nor by the
      concern for the onset of a second primary malignancy.

PMID- 18822696
TI  - Mammographic microcalcification in an autogenously reconstructed breast
      simulating recurrent carcinoma.
AB  - Breast cancer is a common cancer among women. The transverse rectus abdominis
      myocutaneous (TRAM) flap is a popular option because not only does it provide a
      breast with satisfactory bulk composed of autogenous tissue but it also provides
      an abdominal dermolipectomy to the patient. Fat necrosis remains a common problem
      following TRAM flap reconstruction, occurring in 10% to 36% of patients
      undergoing the procedure. A 44-year-old woman underwent a modified radical
      mastectomy followed by pedicled TRAM flap reconstruction after 5 months. Follow
      up mammography 27 months after TRAM flap reconstruction showed a cluster of
      microcalcifications in the deep retroareolar area and recurrent breast carcinoma
      was highly suspected. Physical examination did not detect any abnormality of the
      reconstructed breast. Stereotactic hook localization was performed and an
      excisional biopsy was successfully done. The histological features of the
      resected specimens corresponded to fat necrosis change. Only with the awareness
      of the existence of such entity and careful follow-up can the occurrence of fat
      necrosis in TRAM flap reconstructed breasts be accurately detected and
      appropriately treated.

PMID- 18822697
TI  - Primary infiltrating ductal carcinoma arising in aberrant breast tissue of the
      axilla: a rare entity. Report of a case.
AB  - A 52-year-old woman presented with a palpable nodule in the right axilla.
      Physical examination revealed a 2.5 x 2.5 cm, nontender, firm, brownish, and
      peripherally hyperemic mass with overlying skin retraction on the right anterior
      axillary fold. Bilateral mammogram was negative. Ultrasonography of the right
      axillary region showed a 1.8 x 1.1 cm, poorly defined hypoechoic mass with
      irregular margins and posterior acoustic shadowing. Fine-needle aspiration biopsy
      of the mass revealed malignant epithelial cells. The patient underwent a wide
      local excision of the right axillary lesion with en bloc axillary lymph node
      dissection. Histopathological examination revealed an infiltrating ductal
      carcinoma. Here we report this case of carcinoma originating from aberrant breast
      tissue in the axilla. It is suggested that subcutaneous lesions of uncertain
      origin around the periphery of the breast should be suspected for breast
      carcinoma and treated appropriately.

PMID- 18822698
TI  - Hepatogastric inflammatory pseudotumor presumably deriving from prior amebic
      infection.
AB  - INTRODUCTION: Inflammatory pseudotumor is a rare entity with a clinical and
      radiographic presentation that is difficult to differentiate from malignancy.
      This is a case report of a large hepatogastric inflammatory pseudotumor that
      presumably developed from a prior amebic pseudocyst. CASE REPORT: A 14-year-old
      boy presented with increasing vomiting, epigastric pain, dysphagia, asthenia and
      weight loss. The clinical history included an amebic infection at the age of 2
      months. Instrumental investigations revealed an 8 x 6 cm left subdiaphragmatic
      mass inseparable from the gastric fundus, which appeared to infiltrate the left
      hepatic lobe. Surgery disclosed a bulky mass adhering to the gastric fundus and
      left hepatic lobe that prompted total gastrectomy, resection of the second and
      third hepatic segments, and Roux-en-Y esophagojejunal loop anastomosis. Histology
      subsequently confirmed that this was a pseudocyst with a large calcified nucleus
      surrounded by myofibroblastic proliferation associated with a diffuse
      lymphoplasmacytic infiltrate affecting the gastric wall and hepatic parenchyma,
      hence the final diagnosis of inflammatory pseudotumor, presumably in response to
      a prior amebic pseudocyst. CONCLUSIONS: Inflammatory pseudotumor is a rare entity
      that is seldom found in the stomach. The particular interest of the present case
      lies in the fact that it developed in the stomach and liver, presumably deriving
      from a previous amebic pseudocyst.

PMID- 18822699
TI  - Unusual presentation of metastatic hepatocellular carcinoma in an HIV/HCV
      coinfected patient: case report and review of the literature.
AB  - Hepatocellular carcinoma (HCC) is an increasing cause of mortality in human
      immunodeficiency virus (HIV) seropositive patients. Concurrent infection with HIV
      may accelerate the progression from cirrhosis to HCC. Viral hepatitis and alcohol
      abuse are the main risk factors for HCC in developed countries. Exposure to these
      risk factors is common among HIV-infected patients. We report the case of a 43
      year-old woman affected by HCC, with unusual soft tissue metastases (left
      masseter muscle) and HIV/HCV coinfection. The usual route of metastatic spread
      from classic HCC is hematogenous, with the most common extrahepatic site being
      the lung. Our case, besides the unusual distant metastatic site, showed very
      rapid clinical progression, as has been commonly observed in HIV-infected
      patients with HCC. The case series of HCC in HIV-positive individuals published
      to date does not cumulatively exceed 70 subjects.

PMID- 18822700
TI  - Multiple bowel stenosis and perforation as long-term complications of
      chemoradiotherapy for advanced cervical cancer in a young woman: case report.
AB  - BACKGROUND: Although combined treatment (chemoradiotherapy) appears to improve
      the overall and progression-free survival of patients wih locally advanced
      cervical cancer, some acute toxicity is increased (hematological toxicity,
      nausea, vomiting) while the long-term side effects are unclear. CASE: A 35-year
      old Caucasian woman with a diagnosis of advanced cervical cancer (FIGO stage
      IIIB) was treated with neoadjuvant chemoradiotherapy not followed by radical
      surgery. She underwent whole pelvic radiation therapy for a total of 40 Gy in
      fractions of 2.5 Gy given 4 times per week for 4 consecutive weeks followed by 2
      sessions of intracavitary brachytherapy starting within 7 days of completion of
      external beam radiotherapy (3500 mg/h and 2500-3000 mg/h). Cis-DDP IV was
      administered at a dose of 25 mg/m2 on day 1 and then weekly until completion of
      the radiotherapeutic protocol. After several months the patient presented
      persistent gastrointestinal symptoms and an X-ray showed findings consistent with
      bowel occlusion. The patient underwent emergency surgery and multiple bowel
      stenosis with perforation was diagnosed. DISCUSSION: This is the first report in
      which neoadjuvant chemoradiotherapy is associated with the late complication of
      multiple stenosis and bowel perforation in a young woman with advanced cervical
      cancer. Considering that despite the large number of studies about non-cisplatin
      agents there is not enough evidence to justify treatment with alternative agents,
      this case report might provide new important data regarding the late morbidity of
      cisplatin-based concurrent chemoradiation.

PMID- 18822701
TI  - Primary mucinous adenocarcinoma of appendix treated with chemotherapy and
      radiotherapy: a case report.
AB  - A rare case of primary appendiceal mucinous adenocarcinoma is reported. The
      presenting signs and symptoms were suggestive of acute appendicitis. An
      appendectomy was performed resulting in a histological diagnosis of grade 2
      mucinous adenocarcinoma of the appendix. The patient was referred to our clinic
      where he underwent a complementary right hemicolectomy with lymph node
      dissection. Two of the 17 resected lymph nodes were tumor positive but there was
      no residual tumor in the hemicolectomy specimen. The patient was staged as T4N1M0
      and adjuvant multimodality treatment was planned because he was considered at
      high risk for local-regional recurrence and distant metastasis. Three cycles of
      capecitabine 1250 mg/m2 on days 1-14 and oxaliplatin 130 mg/m2 on day 1, every 21
      days (CAPOX) were administered, then a total dose of 50.4 Gy external-beam
      radiation therapy was delivered to the primary tumor region and 45 Gy to the
      lymphatics, and finally 3 further cycles of the CAPOX regimen were administered.
      Multimodality treatment was well tolerated by the patient, who is still alive 25
      months after the hemicolectomy procedure with no evidence of disease progression.

PMID- 18822702
TI  - Tumor seeding after open nephroureterectomy for ureteral transitional cell
      carcinoma.
AB  - Skeletal muscle metastases following cancer surgery are rare. Few cases of
      abdominal wall metastasis have been reported in the literature and attributed to
      tumor seeding after laparoscopic surgery or percutaneous nephrostomy. We report a
      case of abdominal tumor seeding after open nephroureterectomy managed by means of
      a surgical and medical approach.

PMID- 18822703
TI  - Congenital tumors of the retrorectal space in the adult: report of two cases and
      review of the literature.
AB  - AIMS AND BACKGROUND: To describe and discuss, on the basis of the authors'
      experience and a review of the literature, the main aspects regarding the
      etiology, diagnosis, treatment and prognosis of congenital tumors of the
      retrorectal space. METHODS: We present 2 cases of congenital retrorectal tumors,
      a sacrococcygeal teratoma and a dermoid cyst, which represent, from the
      pathogenetic point of view, the most frequent presentation of the rare tumors of
      the retrorectal space. RESULTS: The reported cases are typical. The teratoma
      presented as an encapsulated, mixed mass located in the pelvic cavity behind the
      rectum and the vaginal canal, without signs of sacral involvement. The dermoid
      cyst appeared as a unilocular lesion filled with sebum and hair, which extended
      laterally to the iliopubic branch, medially to the urethra and anal canal, and
      posteriorly to the adipose tissue of the right buttock. Pelvic MRI produced a
      precise picture of the extension of the lesion and of the relationship between
      the mass and the pelvic organs and surrounding bony structures. Both lesions were
      completely removed via the perineal approach without coccygectomy. No recurrences
      were observed at 2 years of follow-up. CONCLUSIONS: Congenital retrorectal tumors
      are rare. MRI is crucial for diagnosis and preoperative planning. Complete
      surgical removal is the treatment of choice. Resection of the coccyx is necessary
      only in case of its involvement by the neoplastic mass or suspected malignant
      transformation.

PMID- 18822705
TI  - Small-cell lung cancer: an unusual therapeutic approach with more than 10-year
      overall survival. Case report and review of the literature.
AB  - Small-cell lung cancer is the most aggressive lung cancer, with a dismal
      prognosis. The authors present a case report of a patient with limited-stage
      small-cell lung cancer who underwent a thoracotomy for diagnostic purposes, with
      the diagnosis being made after surgical excision. Combination chemotherapy
      remains the cornerstone of treatment for both limited and extensive disease.
      Radiotherapy has been established as an adjunct to chemotherapy in limited-stage
      disease, while in extensive-stage disease it is mostly reserved for the treatment
      of brain metastases. As for surgery, the potential benefits of resection are
      predominantly seen in patients who present with a solitary pulmonary nodule.
      Since small-cell lung cancer becomes highly resistant to chemotherapy, second
      line chemotherapeutic schemes are used for disease progression, with topotecan
      being the highlighted agent. Despite the unusual therapeutic approach, where
      surgery was preferred over the standard diagnostic and staging procedures, the
      patient's more than ten years' survival makes this case presentation a very
      interesting one.

PMID- 18822704
TI  - Laparoscopic treatment of simultaneous splenic lymphangioma and non-Hodgkin's
      lymphoma: report of a case.
AB  - We report, to the best of our knowledge, the first case of simultaneous splenic
      lymphangioma and non-Hodgkin's B-cell lymphoma with liver and bone marrow
      involvement arising in a 69-year-old woman suffering from chronic hepatitis C
      infection treated with laparoscopic splenectomy followed by polychemotherapy.
      After 22 months from surgical treatment, the patient is alive without signs of
      residual disease. According to our experience, laparoscopic splenectomy followed
      by polychemotherapy seems to be an effective treatment for simultaneous splenic
      lymphangioma and non-Hodgkin's B-cell lymphoma.

PMID- 18822706
TI  - An unusual presentation of secondary involvement of B-cell chronic lymphocytic
      leukemia. A case report.
AB  - Extramammary tumors rarely metastasize to the breast. The commonest tumors to
      metastasize in breast tissue are lymphoproliferative diseases, melanoma, lung
      cancer and gynecological malignancies. Primary breast lymphoma has been reported
      in the literature with a maximum percentage of about 0.5% of all breast
      malignancies, while secondary localizations of lymphomas in the breast are less
      well studied in the literature than primary ones. The authors report a rare case
      of a secondary localization of B-cell chronic lymphocytic leukemia to the breast
      in which the diagnosis was obtained by histopathology and immunohistochemistry
      and further confirmed by molecular data. This occurrence must be considered in
      the differential diagnosis of a breast lump so that the primary hematological
      disease can be adequately treated and the correct type of breast surgery
      performed.

PMID- 18822707
TI  - Communication near the end of life.

PMID- 18822709
TI  - Hepatic abscess and silent underlying colon cancer: an emerging association?

PMID- 18822708
TI  - Clinical guidelines in advanced cancer: why we cannot avoid an evidence-based
      model.

PMID- 18822710
TI  - Phase 0 trial as first human study in translational research in medical
      technology.

PMID- 18822711
TI  - [Bevacizumab in the treatment of colorectal carcinoma: news from ASCO 2008].

PMID- 18822712
TI  - [Capecitabine in colorectal carcinoma: news from ASCO 2008]].

PMID- 18822713
TI  - [Docetaxel in the inductive therapy of head and neck cancer: recent evidence].

PMID- 18822714
TI  - [The viewpoint of the medical oncologist].

PMID- 18822715
TI  - [The viewpoint of the radiotherapy oncologist].

PMID- 18822716
TI  - Ike, Katrina not a match. Texas healthcare learns from past devastation.

PMID- 18822717
TI  - Modern Healthcare's 23rd annual Design Awards. Fitting in and standing out.

PMID- 18822718
TI  - The 2008 Greeders' Cup. Distress in financial markets can be blamed on fiscal
      irresponsibility.

PMID- 18822719
TI  - Swamped. Flood forces hospital to change plans from renovation to restoration.

PMID- 18822720
TI  - [3D visualization research on microstructure of human ulnar nerve].
AB  - OBJECTIVE: To explore the application of 3D nerve visualization system in
      processing 2D image information of human ulnar nerve acquired by series freezing
      tissue section, staining and scanning. And to draw the 3D anatomical atlas of
      human ulnar nerve through 3D Nerve visualization software system. METHODS: One
      left ulnar nerve (from medial fasciculus of brachial plexus to transverse carpal
      ligament, about 50 cm) was taken from a fresh donated cadaver. After marked with
      human hair and embedded in OCT, series freezing tissue sections were made and
      stained with acetylcholinesterase histochemically. Series 2D image information
      was obtained through high resolution scanner. Then the microstructure of ulnar
      nerve was reconstructed with 3D Nerve visualization software system. RESULTS:
      Different cross sections of ulnar nerve have different numbers, positions and
      characters of the internal nerve fibers. The microstructure of ulnar nerve could
      be observed in magnifying visual field at any cross section after reconstructed
      in 3D Nerve visualization soft ware system, which made it possible to track
      stereo course of fascicles. CONCLUSION: Reconstructed 3D Nerve visualization
      software system shows the whole microstructure of ulnar nerve and the 3D stereo
      structure of its internal fascicles, thus provides exact topography atlas for
      medical teaching and facilitates precise repair of ulnar nerve injury to improve
      therapeutic effect.

PMID- 18822721
TI  - [Preliminary research of 3D reconstruction of short-segment common peroneal nerve
      functional fascicles].
AB  - OBJECTIVE: To investigate the feasibility of building the 3D reconstruction of
      short segment common peroneal nerve functional fascicles based on serial
      histological sections and computer technology. METHODS: Five cm of the common
      peroneal nerve in the popliteal fossa, donated by an adult, was made into the
      serial transverse freezing sections (n=200) at an interval of 0.25 mm and 10
      microm in thickness per section. Acetylcholinesterase staining was adopted and
      the nerve fascicles were observed by microscope. 2D panorama images were acquired
      by high-resolution digital camera under microscope (x 100) and mosaic software.
      Different functional fascicles were distinguished and marked on each section. The
      topographic database was matched by image processing software. The 3D
      microstructure of the fascicular groups of 5 cm common peroneal nerve was
      reconstructed using Amira 3.1 3D reconstruction software. RESULTS: Based on
      microanatomy and the results of acetylcholinesterase staining, this segmented
      common peroneal nerve functional fascicles was divided into sensory tract, motor
      tract, mixed tract and motor-predominating mixed tract. The cross merging was not
      evident in the nerve fascicles between deep peroneal nerve and superficial
      peroneal nerve, but existed within the functional fascicles of the deep peroneal
      nerve and the superficial peroneal nerve. The results of 3D reconstruction
      reflected the 3D structure of peripheral nerve and its interior functional
      fascicles factually, which displayed solely or in combination at arbitrary
      angles. CONCLUSION: Based on serial histological sections and computer
      technology, the 3D microstructure of short-segment peripheral nerve functional
      fascicles can be reconstructed satisfactorily, indicating the feasibility of
      building 3D reconstruction of long-segmental peripheral nerve functional
      fascicles.

PMID- 18822722
TI  - [Clinical significance of electrophysiological dominance analysis of triceps
      brachii muscle/extensor digitorum communis muscle innervation in ipsilateral C7
      transfer].
AB  - OBJECTIVE: To analysis the electrophysiological dominance weight of the triceps
      brachii muscle/extensor digitorum communis muscle innervated by brachial plexus
      and to conclude its effect on the ipsilateral C7 transfer so as to offer
      electrophysiological data for the safety and indication of ipsilateral C7
      transfer. METHODS: From August 2007 to October 2007, 15 patients with complete
      brachial plexus nerve root avulsion received contralateral C7 transfer. There
      were 13 males and 2 females aged 18-49 years (28 years on average). Injury was
      caused by falling in 1 case, by crush in 2 cases and by traffic accident in 12
      cases, involving left side in 8 cases and right side in 7 cases. The upper,
      middle and lower trunk of the brachial plexus were stimulated respectively, the
      compound muscle action potential (CMAP) at the triceps brachii muscle/extensor
      digitorum communis muscle was recorded, and then the electrophysiological
      dominance weight of the triceps brachii muscle/extensor digitorum communis muscle
      innervated by brachial plexus was confirmed according to the comparison of the
      amplitude percentage of the CMAP by three trunks. The muscle strength of triceps
      brachii muscle/extensor digitorum communis muscle was evaluated and the
      electromyogram was taken 6 months after operation. RESULTS: All patients were
      followed up for 6 months. Concerning the electrophysiological dominance weight,
      the triceps brachii muscle was mainly innervated by upper-middle trunk in 3 cases
      (20%), by middle-lower trunk in 3 cases (20%), by whole trunk in 7 cases (47%)
      and by middle trunk in 2 cases (13%). While the extensor digitorum communis
      muscle was mainly innervated by middle-lower trunk in 3 cases (20%), by whole
      trunk in 10 cases (67%) and by lower trunk in 2 cases (13%). Concerning the
      triceps brachii muscle, 2 patients got the muscle strength of 4 grade with
      recruitment simple phase at 1 month after operation and returned to normal at 3
      month after operation, while 13 patients got the muscle strength of 5 grade with
      recruitment simple or mixed phase at 1 month after operation. Concerning the
      extensor digitorum communis muscle, the muscle strength and the recruitment phase
      of all 15 patients recovered to normal at 1 month after operation. CONCLUSION: To
      patients with various kinds of electrophysiological dominance weight, the cutting
      of C7 does not substantially damage the triceps brachii muscle or extensor
      digitorum communis muscle, indicating that the ipsilateral C7 transfer is safe
      and feasible. However, it should be applied prudently for the patients with high
      dominance weight since it may result in the short-term decrease of triceps
      brachii muscle strength.

PMID- 18822723
TI  - [Short-term efficacy of multiple nerves branch transfer for treating superior
      trunk brachial plexus in jury].
AB  - OBJECTIVE: To recover the loss of the shoulder and elbow function after superior
      trunks injury of brachial plexus through multiple nerves branch transfer
      simultaneously near the nerve entering points of recipient nerves. METHODS: Four
      male patients (aged 21-39 years) with superior trunks injury of brachial plexus
      were treated from February to September 2007. All cases were injured in the
      traffic accident, left side in 1 case and right side in 3 cases, resulting in the
      loss of shoulder abduction, shoulder extorsion, shoulder lift and elbow flexion,
      and the increase of muscle strength of shoulder shrug, elbow extension and finger
      flexion to above or equal to 4th grade. Patients were hospitalized 3-11 months
      after injury. Electromyography showed that the functions of accessory nerve,
      ulnar nerve and the branch to long head of triceps brachii were good, but the
      function of median nerve was injured partially. The following multiple donor
      nerves transfer were performed under general anaesthesia, namely from posterior
      approach accessory nerve to suprascapular nerve, from triceps to axillary nerve,
      from the partial branch of ulnar nerve to the biceps and/or brachial is muscular
      branch of musculocutaneous nerve. RESULTS: All incisions healed by first
      intention. One case suffered postoperative numbness on the ulnar side of hand and
      was symptomatically relieved after expectant treatment, while 3 cases had no
      manifestation of the motor and sensory functional injury related to donor nerve.
      All patients were followed up for 7-12 months. All patients regained the shoulder
      abduction and the elbow flexion 3-4 months after operation and electromyography
      showed that there was the regenerative potential in 3 recipient muscles. The
      shoulder abduction, elbow flexion and the muscle strength of the patients was 30
      65 degrees, 90-120 degrees and 3-4 grade, respectively, 6-7 months after
      operation. Twelve months after operation, the first patient's shoulder abduction,
      external rotation, superinduction and elbow flexion almost returned to normal,
      and his shape of triangular muscle and biceps muscle were nearly normal.
      CONCLUSION: Adopting donor nerves with similar functions to conduct the multiple
      donor nerves transfer in cord level has the advantages of little functional loss
      at the donor sites, and fast and sound functional recovery at the recipient
      sites. It is especially suitable for the superior trunks injury patient with
      delayed treatment and for the patient with the great risk in supraclavicular
      exploration, providing a new approach for treating superior trunks injury of
      brachial plexus.

PMID- 18822724
TI  - [Decompression and anterior transposition of ulnar nerve with inferior ulnar
      collateral artery for cubital tunnel syndrome].
AB  - OBJECTIVE: To report the operation method and the clinical effect of
      decompression and anterior transposition of the ulnar nerve with inferior ulnar
      collateral artery for cubital tunnel syndrome. METHODS: From September 2005 to
      May 2006, 25 cases of cubital tunnel syndrome were treated by the method of
      decompression and anterior transposition of the ulnar nerve with inferior ulnar
      collateral artery. There were 19 males and 6 females with an average of 60 years
      (20-72 years). The disease course was 2 months to 3 years (mean 6.7 months). The
      causes were osteoarthritis in 23 cases, cubital tunnel cyst in 1 case and ulnar
      nerve olisthy in 1 case. According to Pasque grading system for cubital tunnel
      syndrome, 19 cases were graded as good and 6 cases were graded as poor.
      Electrophysiological examination showed the motor nerve conduction velocity of
      the ulnar nerve around the elbow joint was less than 42 m/s. RESULTS: All wounds
      healed by first intention and no operative complications and recurrences
      occurred. All patients were followed up for one year to two and half years (13.9
      months on average). According to Pasque grading system for cubital tunnel
      syndrome, 15 cases were graded as excellent, 9 cases as good and 1 case as fair.
      The excellent and good rate was 96%, indicating a significant difference compared
      with the results before operation (P < 0.05). Electrophysiological examination
      showed the motor nerve conduction velocity of the ulnar nerve around the elbow
      joint was more than 42 m/s. CONCLUSION: The method of decompression and anterior
      transposition of the ulnar nerve with inferior ulnar collateral artery is safe
      and effective for the treatment of cubital tunnel syndrome.

PMID- 18822725
TI  - [Effect of extract of ginkgo biloba leaves on proliferation of SCs cultured in
      vitro].
AB  - OBJECTIVE: To investigate the effect of extract of ginkgo biloba leaves (EGb50)
      on the proliferation of SCs cultured in vitro. METHODS: The SCs were isolated
      from 3-day-old SD rats' sciatic nerves by the method of enzyme gradation
      digestion (n=20) and the purified 2nd passage of SCs were divided into 2 groups:
      the experimental group, in which SCs were cultured in FBS-DMEM medium with EGb50
      (terminal concentration: 50 microg/mL); the control group, in which SCs were
      cultured in the FBS-DMEM medium without EGb50. The absorbance (A) value was
      detected by the 2, 3-bis- (2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5
      carboxanilide (XTT) method 1, 3, 5, 7 and 9 days after culture, then the growth
      curves was drawn. Cell cycle was detected by flow cytometry (FCM). Disintegration
      per minute (DPM) of SCs was detected by the method of 3H-thymine nucleoside (3H
      TdR) 2 and 3 days after culture and nerve growth factor (NGF) synthesis in SCs
      culture media was detected by ELISA method. RESULTS: Most SCs were spindle-shaped
      with a purity above 90%. XTT detection showed that A value of SCs in the control
      group was gradually increased 3 days after culture, reached the peak 5 days after
      culture and gradually decreased from then; the A value in the experimental group
      experienced the similar changes, but it was higher than that in the control group
      at each time point (P < 0.01). 3H-TdR showed that the DPM of the experimental
      group was 1 961.78 +/- 231.13 and 4 601.51 +/- 605.08 at 2 and 3 days after
      culture, while for the control group, the A value was 1347.15 +/- 121.57 and
      3740.42 +/- 158.73 at the same time point, indicating a significant difference
      between two groups (P < 0.01). FCM observation indicated that the SCs
      proliferation index of the experimental group and the control group was 18.6% +/-
      3.2% and 9.7% +/- 2.9%, indicating a significant difference between two groups (P
      < 0.01). ELISA observation showed that the NGF concentration in the experimental
      and the control group was (0.0656 +/- 0.0039) ng/mL and (0.0386 +/- 0.0036)
      ng/mL, indicating a significant difference (P < 0.01). CONCLUSION: EGb50 is
      capable of enhancing the proliferation of SCs cultured in vitro, which may be one
      of the important mechanisms to promote peripheral nerve regeneration.

PMID- 18822726
TI  - [Experimental study on neural stem cell transplantation delaying denervated
      muscle atrophy].
AB  - OBJECTIVE: To observe the delaying effect of neural stem cell (NSC)
      transplantation on denervated muscle atrophy after peripheral nerve injury, and
      to investigate its mechanism. METHODS: NSCs were separated from the spinal cords
      of green fluorescent protein (GFP) transgenic rats aged 12-14 days mechanically
      and were cultured and induced to differentiate in vitro. Thirty-two F344 rats,
      aged 2 months and weighed (180 +/- 20) g, were randomized into two groups (n=16
      per group). The animal models of denervated musculus triceps surae were
      established by transecting right tibial nerve and common peroneal nerve 1.5 cm
      above the knee joints. In the experimental and the control group, 5 microL of GFP
      NSC suspension and 5 microL of culture supernatant were injected into the distal
      stump of the tibial nerve, respectively. The general condition of rats after
      operation was observed. At 4 and 12 weeks postoperatively, the wet weight of
      right musculus triceps surae was measured, the HE staining, the Mallory trichrome
      staining and the postsynaptic membrane staining were adopted for the histological
      observation. Meanwhile, the section area of gastrocnemius fiber and the area of
      postsynaptic membrane were detected by image analysis software and statistical
      analysis. RESULTS: The wounds in both groups of animals healed by first
      intension, no ulcer occurred in the right hind limbs. At 4 and 12 weeks
      postoperatively, the wet weight of right musculus triceps surae was (0.849 +/-
      0.064) g and (0.596 +/- 0.047) g in the experimental group, respectively, and was
      (0.651 +/- 0.040) g and (0.298 +/- 0.016) g in the control group, respectively,
      showing a significant difference (P < 0.05). The fiber section area of the
      gastrocnemius was 72.55% +/- 8.12% and 58.96% +/- 6.07% in the experimental
      group, respectively, and was 50.23% +/- 4.76% and 33.63% +/- 4.41% in the control
      group, respectively. There were significant differences between them (P < 0.05).
      Mallory trichrome staining of muscle notified that there was more collagen fiber
      hyperplasia of denervated gastrocnemius in the control group than that in the
      experimental group at 4 and 12 weeks postoperatively. After 12 weeks of
      operation, the area of postsynaptic membrane in the experimental group was
      (137.29 +/- 29.14) microm2, which doubled that in the control group as (61.03 +/-
      11.38) microm2 and was closer to that in normal postsynaptic membrane as (198.63
      +/- 23.11) microm2, showing significant differences (P < 0.05). CONCLUSION: The
      transplantation in vivo of allogenic embryonic spinal cord NSCs is capable of
      delaying denervated muscle atrophy and maintaining the normal appearance of
      postsynaptic membrane, providing a new approach to prevent and treat the
      denervated muscle atrophy clinically.

PMID- 18822727
TI  - [Primary study on effect of various components of modified formula radix hedysari
      on peripheral nerve regeneration].
AB  - OBJECTIVE: To investigate the effects of icariin and mixed prescription of
      icariin, radix hedysari polysaccharide, and liquid extracted from earthworm on
      peripheral nerve regeneration. METHODS: Twenty male SD rats weighing (200 +/- 10)
      g were selected and randomized into four groups (n=5 per group): sham operated
      group (group A), model group (group B), icariin group (group C), and mixed liquid
      group (group D). In group A, the left sciatic nerves of the rats were only
      exposed, and treated at fixed time from the following day with the NS (2 mL/d).
      In groups B, C, D, the models were made by clamping sciatic nerve and treated
      with NS, icariin and mixed liquid, respectively (2 mL/d). The general state of
      animals was observed after the treatment daily. The nerve function index, motor
      nerve conductive velocity and the amorphous and number of myelinated sciatic
      nerve fibers were measured at 21 days. RESULTS: Animals in various groups were
      all in good state. After 21 days, the weights of rats in groups A, B, C and D
      were (366.9 +/- 14.0), (370.1 +/- 16.3), (373.3 +/- 19.6) and (374.0 +/- 11.4) g,
      respectively, and there was no significant difference among these groups (P >
      0.05). For sciatic function index, there was no significant difference between
      group A and group D (P > 0.05), between group B and group C (P > 0.05), while
      there was significant difference between group B and group D (P < 0.05). For
      tibial function index, there was significant difference between group A and
      groups B, C, D (P < 0.05), there was no significant difference between group B
      and groups C, D (P > 0.05). For peroneal function index, there was no significant
      difference between group A and groups C, D (P > 0.05), between group B and groups
      C, D (P > 0.05). The sciatic motor nerve conductive velocities of group A, B, C
      and D were (45.0 +/- 2.9), (8.0 +/- 2.6), (13.4 +/- 6.8), and (19.6 +/- 9.3) m/s,
      respectively, there was no significant difference between group B and group C (P
      > 0.05), and there was significant difference between group A and groups B, C, D
      and between group B and group D (P < 0.05). The size of individual myelinated
      sciatic nerve fibers of regenerated nerves in groups B, C, and D was
      significantly smaller than that in group A. Comparing with group A, the number of
      myelinated sciatic nerve fibers in groups B, C, and D was 93.3% +/- 35.6%, 90.6%
      +/- 37.1%, and 115.4% +/- 40.6%, respectively, but there was no significant
      difference among four groups (P > 0.05). CONCLUSION: Icariin and mixed
      prescription are safe. The improving peripheral nerve regeneration effect of
      mixed prescription is more obvious than that of icariin, indicating the
      comprehensive study of modified formula radix hedysari is necessary to find the
      effective part or mixture of effective compounds with fixed percentage.

PMID- 18822728
TI  - [Experimental study on the functional reserve of ulnar nerve in rats].
AB  - OBJECTIVE: To study the functional change of nerve trunk after removing the
      partial bundles of ulnar nerve, to propose the concept of functional reserve of
      peripheral nerves and to investigate the functional reserve quantity of
      peripheral nerves. METHODS: Two hundred and twenty SD rats (male or female),
      aging 3 months and weighing 300-350 g, were randomized into the experimental
      group and the control group (n=110 per group). And the experimental group was
      subdivided into group 1/8, group 1/4, group 1/3, group 1/2 and group 2/3
      according to the resection portion (n=22 per group). In the experimental group,
      the section of the lowest level on ulnar nerve trunks was exposed, and a certain
      portion of its bundles was separated and cut, while in the control group the
      bundles were only separated without resection. The general condition of all rats
      was observed, and the motoneurons in cornu anterius medullae spinalis were
      detected at 1 week, 2 weeks and 2 months after operation. The neuro
      electrophysiology and the function of dominated muscles were detected at 2 weeks,
      2 months, 3 months, and 4 months after operation. RESULTS: All the rats survived
      without infection and obvious ulcer in the limbs. The number of motoneurons in
      cornu anterius medullae spinalis in various experimental subgroups witnessed no
      obvious changes (P > 0.05). The superstructure changed obviously at the early
      postoperative stage in group 1/2 and group 2/3, but restored well at 2 months
      after operation. For the latent period of evoked potential, there was no
      significant difference between the various experimental subgroups and the control
      group at each time point (P > 0.05), but there was a significant difference among
      the various experimental subgroups when compared the time points of 2, 3 and 4
      months to that of 2 weeks (P < 0.05) and no statistically significant difference
      at other time points (P > 0.05). For the wave amplitude of evoked potential of
      motor nerves, the maximum wave amplitude and the persistence time of the dominate
      muscle, there were significant differences between the various experimental
      subgroups and the control group at each time point (P < 0.05), and there were
      significant differences among the various experimental subgroups when comparing
      the time points of 2, 3 and 4 months to that of 2 weeks (P < 0.05) and no
      statistical significance at other time points (P > 0.05). CONCLUSION: The
      functional reserve of the ulnar nerve without compromise accounts the 1/3 of the
      whole trunk diameter.

PMID- 18822729
TI  - [Experimental study on the improving effect of motor nerve babysitting on delayed
      nerve anastomosis].
AB  - OBJECTIVE: To observe whether the motor nerve babysitter could improve the
      delayed nerve anastomosis and promote the functional recovery. METHODS: Sixteen
      SD rats weighing 200-250 g were randomly divided into 2 groups. In group A, the
      left musculocutaneous nerve was transected to make the model of biceps brachii
      denervation and anastomosed to its proximal end 6 weeks later; In group B, the
      musculocutaneous nerve was transected and the distal end was coapted to the
      purely motor medial pectoral nerve immediately (nerve babysitter) and the
      musculocutaneous nerve was separated from the medial pectoral nerve, and
      reanastomosed to its proximal end 6 weeks later. In the animal model, the left
      limbs served as experimental sides, the right limbs as control sides. After 6 and
      12 weeks of the second surgery, behavioral test (grooming test) was performed and
      the degree of the biceps brachii atrophy was observed, the latent period and the
      amplitude of the maximum action potentials of the biceps brachii were detected,
      the wet muscle weight, muscle fiber cross-section area and the activity of Na+-K+
      ATPase of the biceps brachii were measured. RESULTS: After 4 weeks of the second
      surgery, grooming behavior was found in group B, while few grooming behavior was
      seen in group A till 6 weeks after the secondary surgery. After 6 weeks of the
      second surgery, the recovery rate of the latent period and the amplitude, the wet
      muscle weight, muscle fiber cross-section area and the enzymatic activity of Na+
      K+-ATPase of the biceps brachii in group A was 187.25% +/- 1.97%, 46.25% +/-
      4.63%, 55.14% +/- 1.99%, 49.97% +/- 1.71%, and 65.81% +/- 2.24%, respectively,
      which was significantly different from that in group B (155.96% +/- 3.02%, 51.21%
      +/- 2.13%, 74.18% +/- 1.82%, 55.05% +/- 1.64% and 71.08% +/- 1.53%, respectively,
      P < 0.05). After 12 weeks of the second surgery, the recovery rate of the latent
      period and amplitude, the wet muscle weight, muscle fiber cross-section area and
      the enzymatic activity of Na+-K+-ATPase of the biceps brachii in group A was
      145.36% +/- 3.27%, 51.84% +/- 5.02%, 77.92% +/- 1.73%, 61.04% +/- 2.68% and
      71.94% +/- 1.65%, respectively, which was significantly different from that in
      group B (129.83% +/- 8.36%, 75.22% +/- 2.78%, 84.51% +/- 1.34%, 78.75% +/- 3.69%
      and 84.86% +/- 1.81%, respectively, P < 0.05). CONCLUSION: Motor nerve
      babysitting could reduce muscular damage after denervation, improve the effect of
      delayed nerve repair and promote the functional recovery of musculocutaneous
      nerve.

PMID- 18822730
TI  - [Time limit of repairing old sciatic nerve defect in rats].
AB  - OBJECTIVE: To investigate the time limit of repairing old sciatic nerve defect in
      rats and observe the repair effect of autogenous nerve transplantation on old
      sciatic nerve defect in rats. METHODS: Thirty-six SD rats of clean grade were
      randomized into 6 groups (n=6 per group). The animal model of nerve defect was
      made by transecting left sciatic nerve at the mid-thigh level. For groups A1, B1
      and C1, defects were repaired by the contralateral autogenous nerve
      transplantation 1, 3 or 6 months after nerve damage and for the control groups of
      A2, B2 and C2, defects were not repaired. After operation, the gait, toe skin and
      leg muscle were examined weekly. Three months after autograft, a combination of
      electrophysiology examination, fluoro gold (FG) retrograde tracing and
      histological assessment including light microscopy, TEM was utilized to
      investigate the nerve functional recovery. RESULTS: Lameness and foot skin ulcers
      were observed in each group after nerve damage. At 2 months after autograft, such
      denervation symptoms were only improved in groups A1 and B1. At 3 months after
      autograft, the motor conduction velocity was (21.84 +/- 6.74), (20.02 +/- 4.17)
      and (16.09 +/- 8.21) m/s in groups A1, B1 and C1, respectively, showing no
      statistically significant difference between them (P > 0.05). The amplitude of
      compound muscle action potential (CAMP) was (12.68 +/- 4.38), (9.20 +/- 3.43) and
      (1.22 +/- 0.39) mV in groups A1, B1 and C1, respectively, indicating significant
      differences between groups A1, B1 and group C1 (P < 0.05). No CAMP was evident in
      groups A2, B2 and C2. FG retrograde tracing conducted 3 months after autograft
      showed that the positive cells were most common in group A1 with big soma, mild
      in group B1 and lest in group C1 with smallest soma. Gastrocnemius Masson
      staining showed that the fiber morphology of gastrocnemius in groups A1 and B1
      was close to normal, while the rest 4 groups had an obvious atrophy of muscle
      fiber. The fiber cross-section area was (340.73 +/- 118.46), (299.88 +/- 119.75),
      (54.33 +/- 53.43), (78.60 +/- 51.38), (65.62 +/- 25.36), and (40.93 +/- 28.22)
      microm2 in groups A1, B1, C1, A2, B2 and C2, respectively, indicating a
      significant difference between groups A1, B1 and groups C1, A2, B2 (P < 0.05).
      Neurohistology observation showed that more regenerated nerve fibers were
      observed in group A1 and B1, but less in group C1. The myelin sheath was thick in
      groups A1 and B1, while it was thin in group C1. Only SCs and hyperplastic
      collagen fiber were found in groups A2, B2 and C2. CONCLUSION: Autogenous nerve
      transplantation is capable of repairing 1- and 3-month sciatic nerve defect to
      some degree in rat, but repair effect is not obvious on 6-month sciatic nerve
      defect in rats.

PMID- 18822731
TI  - [Experimental study on peripheral nerve plasticity in rats].
AB  - OBJECTIVE: To observe the plastic changes of sensory nerve in terms of structure
      and function when target organ changed through making the rat model of nerve
      regeneration by anastomosing the proximal end of sensory nerve and the distal end
      of motor nerve. METHODS: Thirty adult SD rats (male or female), weighing 200-250
      g, were randomized into three groups (n=10 per group). The left upper limb of the
      each rat was used as the experimental side, while the right upper limb as the
      control side. In group A, the medial antebrachial cutaneous nerve was cut 5 mm
      away from its origin and its proximal end was anastomosed end-to-end to the
      distal end of musculocutaneous nerve. In group B, the musculocutaneous nerve was
      cut 5 mm away from its nerve entry point and the proximal end of medial
      antebrachial cutaneous nerve were anastomosed end-to-end to the distal end of
      musculocutaneous nerve. In group C, medial antebrachial cutaneous nerve and
      musculocutaneous nerve were cut, without further anastomosis. Twenty-four weeks
      after operation, the general condition and the motion of the elbow joint of rats,
      the wet weight and muscle fiber cross-section area of the biceps brachii as well
      as the latent period and the amplitude of the evoked potential were observed and
      the acetylcholinesterase (AchE) staining of nerve of proximal end of anastomosis
      was conducted. RESULTS: All the rats survived for 24 weeks with good general
      condition and without wound infection. The rats in groups A, B and C were lost
      the active flexion of left elbow joint after operation. The rats in groups A and
      B got recovered to some degree at 24 weeks. The behavioral evaluation showed that
      there were 7 limbs in group A and 5 limbs in group B scored as 4-5 points, there
      was a significant difference when compared with group C (P < 0.05), but there was
      no significant difference between group A and group B (P > 0.05). Group A and
      group B were superior to group C in terms of the wet weight and the muscle fiber
      cross-section area of the biceps brachii (P < 0.05), but no significant
      difference between group A and group B was detected (P > 0.05). The evoked
      potential of the biceps brachii and motor nerve fibers in proximal end of
      anastomosis could be detected in both group A and group B. But there was no
      significant difference between group A and group B with respects of function
      recovery of elbow joint, the latent period and the amplitude of the evoked
      potential of the biceps brachii and the quantity of motor nerve fiber in proximal
      end of anastomosis (P > 0.05). CONCLUSION: The change of target organ leads to
      the sensory nerve plasticity structurally and functionally, which may provide a
      new approach for peripheral nerve repair.

PMID- 18822732
TI  - [Spinal pathologic changes and axonal regeneration after brachial plexus root
      anastomosis in rats].
AB  - OBJECTIVE: To evaluate the feasibility of direct anastomosis in the rat model of
      the brachial plexus extravertebral foramen nerve root division of C5-7. Methods
      Forty-eight SD rats (male or female) aging 4-6 months and weighing 250-300 g were
      selected to make the model of extravertebral foramen nerve root division of C5-7.
      The left C5-7 nerve roots, as the experimental sides, were separated to the
      brachial plexus nerve trunk and the transected roots were sutured to the proximal
      stump immediately after cutting off the brachial plexus extravertebral foramen
      nerve root division. The right C5-7 nerve roots, as the control sides, received
      no operation. The general condition of rats after operation was observed. The
      gross observation, the histological observation and BDA nerve tracing technology
      were adopted to observe the wet weight of musculus biceps brachii, the cross
      section of biceps brachii and the spinal cord and distal nerve trunk at 3 weeks,
      3 months and 6 months after operation. Results All rats survived well after
      operation. Claudication and unfold claw reflex were observed in the experimental
      sides, and the unfold claw reflex disappeared 3 months later. Comparatively, the
      control sides were normal. Nerve adhesion aggravated gradually and the neural
      stems were shriveled within 6 months after operation in the experimental sides.
      Comparatively, the control sides were normal. The wet weight of biceps brachii in
      the experimental sides and the control sides at 3 weeks, 3 months and 6 months
      after operation was (0.28 +/- 0.12), (1.37 +/- 0.33), (0.58 +/- 0.10), (1.36 +/-
      0.35), (1.39 +/- 0.31), (1.37 +/- 0.38) g, respectively, indicating significant
      differences between two sides at 3 weeks and 3 months (P < 0.05), but no
      significant difference at 6 months (P > 0.05). The modified Marsland and the LFB
      staining of spinal cord and superior trunk of brachial plexus showed that the
      number of neurons, cell nuclear and Nissl body decreased and cell bodies changed
      from swelling to shrinkage, dyeing nerve fibers increased, neural axone was thin
      and myelin sheath was slightly stained at each time point in experimental side.
      The number of motor neurons in cornu anterius medullae spinalis in the
      experimental side was 84.5% +/- 3.2%, 74.4% +/- 4.5%, 73.7% +/- 3.8% of that in
      the control side at each time point, respectively. HE staining of biceps brachii
      detected that the muscle denaturation was very serious at 3 months after
      operation and then recovered. Neural tracing used BDA showed that the closer to
      the proximal of nerve trunk, the more obviously stained it was of myelin sheath
      and the more massive of axon at 6 months after operation. And there was almost no
      myelin and axon stained in musculocutaneous nerve. CONCLUSION: In the rat model
      of brachial plexus extravertebral foramen nerve root division, the motoneuron in
      cornu anterius medullae spinalis necrosis rate reaches 20%-30%, and most of the
      residual neurons are pathologic. The regenerated fibers manifest as insufficient
      dynamic power and incomplete development, making no sense for the recovery of end
      organ function. Therefore, the exact mechanism of the recovery of biceps brachial
      muscle demands further study.

PMID- 18822733
TI  - [Study on treating residual cavity of body surface after abscess drainage by
      sodium hyaluronate hydrogel].
AB  - OBJECTIVE: To study the effect of sodium hyaluronate hydrogel in treating
      residual cavity on body surface after abscess drainage so as to provide new
      method to speed up the healing of residual cavity after body surface abscess
      drainage and reduce the frequency of dressing change and clinic nursing workload.
      METHODS: From June 2007 to March 2008, 60 outpatients with body surface abscess
      drainage were randomly divided into hydrogel group (group A, 30 cases) and the
      control group (group B, 30 cases). In group A, there were 16 males and 14 females
      aged (49.5 +/- 6.1) years, the disease course was (3.8 +/- 0.6) days, and the
      volume of residual cavity was (4.19 +/- 1.31) mL. In group B, there were 18 males
      and 12 females aged (50.2 +/- 7.6) years, the disease course was (4.3 +/- 0.5)
      days, and the volume of residual cavity was (4.04 +/- 1.22) mL. There was no
      significant difference between two groups in gender, age, disease course and
      volume of residual cavity (P > 0.05). Residual cavity was smeared with 1 mL/cm2
      sodium hyaluronate hydrogel in group A and drained by saline gauze in group B,
      the dressing was changed every two to three days. Residual cavity volume was
      recorded every four days, and the residual cavity volume, the frequency of out
      patient dressing and the healing time residual of cavity were compared. RESULTS:
      The volume of residual cavity was (3.11 +/- 1.12), (1.75 +/- 0.95) and (0.55 +/-
      0.56) mL in group A, and was (3.39 +/- 1.12), (2.64 +/- 0.99) and (1.81 +/- 0.81)
      mL in group B at 4, 8 and 12 days after treatment respectively, showing no
      significant differences at 4 days (P > 0. 05), but significant difference at 8
      and 12 days (P < 0.01). Residual cavity healing time was (12.70 +/- 2.78) days in
      group A and (20.27 +/- 3.89) days in group B, and the frequency of dressing
      change was 5.53 +/- 1.33 in group A and 9.13 +/- 1.81 in group B, indicating
      significant differences between two groups (P < 0.01). CONCLUSION: Sodium
      hyaluronate hydrogel can promote residual cavity healing, reduce the frequency of
      dressing change of out-patient and decrease the clinic nursing care workload.

PMID- 18822734
TI  - [Treating complex renal aneurysm with ex vivo aneurysmectomy and
      autotransplantation].
AB  - OBJECTIVE: To discuss the safety and feasibility of treating complex renal
      aneurysm with ex vivo aneurysmectomy and renal revascularization and renal
      autotransplantation after hand-assisted retroperitoneoscopic nephrectomy.
      METHODS: In October 2006, one male patient with complex renal aneurysm was
      treated. The preoperative color Doppler ultrasonograph, CT and DSA showed that
      there was an aneurysm (3.4 cm x 4.3 cm x 4.5 cm) located in the main renal artery
      bifurcation and its five branches of the left kidney. The patient had a history
      of hypertension with no response to treatment. After successful hand-assisted
      retroperitoneoscopic nephrectomy, the kidney off-body was perfused by the renal
      irrigating solution immediately to protect the kidney. Then ex vivo
      aneurysmectomy and renal artery revascularization were performed, the renal
      artery was reconstructed with an autologous right internal iliac artery. The
      reconstructed left kidney was re-implanted into the right iliac fossa. RESULTS:
      The operation was successful and the patient recovered without perioperative
      complications. The postoperative renal function was normal and the color Doppler
      ultrasonograph showed that the blood circulation in the transferred renal artery
      of the right iliac fossa and its branches was smooth, the blood circulation of
      the renal venous was smooth and no stenosis in the ureter 2 weeks after
      operation. Thirteen months follow-up showed the blood pressure was recovered to
      normal and the renal function was normal. CONCLUSION: The method of ex vivo
      aneurysmectomy and autotransplantation is safe, feasible and minimally invasive
      for treating complex hilar renal artery aneurysms.

PMID- 18822735
TI  - [Investigation of new classification and repair methods for fingertip traverse
      amputation].
AB  - OBJECTIVE: To investigate new classification and repair methods for the traverse
      amputated fingertip. METHODS: From March 2000 to October 2006, 20 cases of 20
      fingers with traverse amputated fingertip, including 13 males and 7 females aged
      17-47 years, were treated. Twenty patients (9 crush injuries, 5 cutting injuries
      and 6 sawing injuries) were classified into 4 types, namely type I (the distal
      one third of nail bed), type II (the middle of nail bed), type III (the proximal
      one third of nail bed), and type IV (the root of nail bed). There were 3 patients
      (2 index fingers and 1 little finger) of type I, 8 patients (2 thumbs, 3 index
      fingers and 3 middle fingers) of type II, 5 patients (3 index fingers, 1 ring
      finger and 1 little finger) of type III, and 4 patients (2 thumbs, 1 middle
      finger and 1 little finger) of type IV. The soft tissue defect ranged from 1.2 cm
      x 1.2 cm to 1.5 cm x 1.2 cm. The time from injury to surgery was 3-10 hours.
      Fingers of type I and type II were treated with forward flow axial flap and
      modified nail bed lengthening. Fingers of type III and type IV were treated with
      forward flow axial flap and partial nail bed replantation as well as modified
      nail bed lengthening. The flaps ranged in size from 1.5 cm x 1.2 cm to 2.0 cm x
      1.4 cm. RESULTS: Twenty patients incisions healed by first intention and the
      flaps, nails and skin grafting survived. All donor sites healed by first
      intention. All patients were followed up for 2-6 months (4 months on average).
      The appearances of fingertips were good. The texture of the flap was soft, and
      the fingers had no tenderness and motor disturbance. The two-point discrimination
      was 4.5-6.5 mm. The finger nails of type I and type II extended 3-4 mm after
      operation, while the finger nails of type III and type IV extended 8-10 mm after
      operation. All finger nails were smooth and flat without pain. Hook nail happened
      in 1 case 6 months after operation. CONCLUSION: Classification of the injured
      fingers according to the condition of the amputation base is helpful in choosing
      repair methods, and is conducive to maximize the recovery of the function and
      shape of fingertips.

PMID- 18822736
TI  - [Microvascular decompression for cranial nerve hyperactive dysfunction].
AB  - OBJECTIVE: To assess the results of microvascular decompression (MVD) in treating
      cranial nerve hyperactive dysfunction. METHODS: From October 2002 to January
      2007, 106 patients with cranial never hyperactive dysfunction were treated with
      MVD. Among them, there were 47 males and 59 females with an average age of 62
      years (42-85 years), including 56 cases of trigeminal neuralgia, 33 cases of
      hemifacial spasm and 17 cases of spasmodic torticollis. MRI showed obvious nerve
      root compression in 60 patients (56.6%), suspected nerve root compression in 33
      patients (31.1%) and no nerve root compression in 13 patients (12.3%). The
      disease course was 2-300 months with median course of 54 months. The typical
      manifestations before operation were pain and myospasm in corresponding
      innervation region. RESULTS: The superior cerebellar artery was the most common
      offending vessel in trigeminal neuralgia (44.6%, 25/56), the anterior inferior
      cerebellar artery in hemifacial spasm (33.3%, 11/33), and the vertebra-basilar
      artery in spasmodic torticolis (82.4%, 14/17). Complications of facial paralysis,
      hypoacusia, facial numbness, dizziness, pain of neck and shoulder, muscles
      weakness of neck and subcutaneous dropsy occurred in 31 patients (29.2%). All
      patients were followed up for 6-42 months. The total response rate was 90.6%. The
      curative rate of MVD was 83.9% (47/56) in trigeminal neuralgia, 81.8% (27/33) in
      hemifacial spasm and 41.2% (7/17) in spasmodic torticolis, respectively. Five
      patients failed to response (4.7%), 2 of them were cured after re-operation and 3
      abandoned further treatment. Five patients suffered recurrence 3-8 months after
      operation (4.7%), 2 of them recovered after re-operation, 1 got relief by Gamma
      knife treatment, and 2 abandoned further treatment. CONCLUSION: MVD has a good
      therapeutic effect on the disease caused by vascular compression of cranial
      nerve. Comprehensive preoperative evaluation, skillful operational technique and
      intraoperative electrophysiological monitoring should be implemented to enhance
      the therapeutic effects of MVD and to prevent possible complications.

PMID- 18822737
TI  - [MRI diagnosis of sacral fracture with sacral neurological damage and its
      clinical application].
AB  - OBJECTIVE: To study the MRI diagnosis of sacral fracture with sacral neurological
      damage and its clinical application. METHODS: From October 1999 to October 2007,
      20 cases of sacral fracture (Denis classification, Type II) with sacral
      neurological damage were examined by oblique coronal MRI of sacrum to show the
      whole length of sacral nerve. There were 17 males and 3 females, aged 30-55
      years. The time from injury to hospitalization varied from 1 day to 23 months.
      The injury was caused by traffic accident in 10 cases, smash of heavy object in 8
      cases and crush in 2 cases. Eight cases were accompanied by pubis fracture and 4
      cases by urethral disruption. All patients accepted the examination of X-ray, CT
      and spiral CT 3D reconstruction. X-ray showed the displacement of fracture
      fragment was backwards and upwards, and sacral-hole line was vague, asymmetric
      and distorted. CT showed that sacral neural tube was left-right asymmetry, the
      displacement of fracture fragment was backwards and upwards, combining with the
      compression and intruding to sacrum center at different section levels. The
      clinical manifestations, international standards for Neurological Classification
      of Spinal Cord Injury recommended by American Spinal Injury Association
      International Spinal Cord Society, comparison between normal and abnormal MRI and
      Gierada's results were the basis for clinical diagnose and MRI diagnose, which
      was confirmed by operation. RESULTS: Nerve injury diagnosed by clinical
      manifestation were S1 (17 cases), S2 (14 cases), S3 (7 cases), and S4 (6 cases).
      Nerve injury diagnosed by MRI were S1 (17 cases), S2 (14 cases), S3 (3 cases),
      and S4 (2 cases). Nerve injury confirmed by operation were S1 (17 cases), S2 (14
      cases), S3 (7 cases), and S4 (1 case). Oblique coronal MRI of sacrum showed the
      whole length of sacral nerve and its adjacent relationship, detecting bone
      fragment compression and route alteration of never were evident in 5 cases, the
      fat disappearance around the site of nerve root injury in 19 cases, narrowness of
      sacral nerve canal in 17 cases and the abnormally enlarged sacral nerve in 11
      cases. CONCLUSION: Oblique coronal MRI of sacrum is of great value in the
      localization and the qualitative diagnosis of sacral neurological damage.

PMID- 18822738
TI  - [Introduction of amyotrophic lateral sclerosis self-assessment scale].
AB  - OBJECTIVE: To introduce a new functional self-assessment scale of amyotrophic
      lateral sclerosis (ALS). METHODS: By comparing current different ALS functional
      scales and combining relative clinical experience and numeric pain intensity
      scale, ALS self-assessment scale was set down by International Association of
      Neural Restoration. RESULTS: ALS self-assessment scale included 3 categories with
      18 items, adopting 10 points grading system, namely 10 was defined as the normal,
      0 as the worst, and the total scores was 180. This scale included: (1) Bulbus
      medullae function: speech, swallowing, salivation, and tongue extension. (2)
      Limbs function: left arm movement, left hand movement, right arm movement, right
      hand movement, left leg movement, right leg movement, trunk movement, head-up,
      walking, and climbing stairs. (3) Others: breathing, muscular tone, pain, and
      muscle discomfort. CONCLUSION: ALS self-assessment scale is specifically designed
      for ASL patients. It can evaluate patient's function comprehensively and is
      simple and convenient, consuming less time.

PMID- 18822739
TI  - [Phosphoinositide 3-kinase/Akt pathway involved in regulation of hypoxia
      inducible factor 1alpha in hypoxia ischemia brain damage of neonatal rats].
AB  - OBJECTIVE: To investigate the expression of hypoxia inducible factor 1alpha (HIF
      1alpha) protein and the activation of phosphoinositide 3-kinase/Akt (PI3K/Akt)
      signaling pathway in neurons under hypoxia ischemia condition, and to elucidate
      the role of PI3K/Akt on HIF-1alpha regulation in the developing neurons after
      hypoxia ischemia brain damage (HIBD). METHODS: Fifty-six SD rats aged 10 days
      were randomly divided into normal control group (n=12), sham operation group
      (n=12), experimental group (n=24), wortmannin treated group (n=4) and DMSO/PBS
      treated group (n=4). In the experimental group, the rats were anesthetized with
      ethyl ether. The right common carotid artery was exposed and ligated. Then, they
      were exposed to hypoxia in a normobaric chamber filled with 8% oxygen and 92%
      nitrogen for 2.5 hours. In the sham control group, the right common carotid
      artery was exposed but was not ligated or exposed hypoxia. In the normal control
      group, the rats received no further processing. For wortmannin treated group and
      DMSO/PBS treated group, the rats received intraventricular injection of
      wortmannin or DMSO/PBS 30 minutes before hypoxia ischemia. The brain tissues were
      harvested from the rats in the normal control, sham operation and experimental
      groups at 4, 8 and 24 hours after hypoxia ischemia, but in the wortmannin and
      DMSO/PBS treated groups only at 4 hours. The HIF-1alpha protein expression and
      Akt protein expression were detected with immunohistochemistry method. HIF
      1alpha, Akt and p-Akt protein expression were measured by Western blot analysis.
      RESULTS: In the experimental group, the HIF-1alpha expression was significantly
      increased at 4 hours after operation, reached the peak level at 8 hours, and
      began to decrease at 24 hours. The p-Akt protein was significantly increased at 4
      hours, and began to decrease at 8 hours. However, the expression levels of HIF
      1alpha and p-Akt protein in the normal control group were extremely low at each
      time point. So, the expression levels of HIF-1alpha in the experimental group was
      significantly higher than that in the normal control groups (P < 0.01), the
      expression of p-Akt protein in the experimental group at 4 and 8 hours was
      significant higher than that in the normal control group (P < 0.05). The change
      of Akt protein in the experimental group was not time-dependent, and no
      significant difference was evident when compared with that of the normal control
      group (P > 0.05). Using wortmannin, the PI3K/Akt specific inhibitor, HIF-1alpha
      protein expression was significantly decreased when compared with the DMSO/PBS
      treated group and experimental group (P < 0.01). CONCLUSION: These results
      suggested that the HIBD of neonatal rats may activate PI3K/Akt signaling pathway
      and further induce the expression of HIF-1alpha, indicating PI3K/Akt signaling
      pathway and HIF-1alpha could be a potential target for treatment of neonatal
      HIBD.

PMID- 18822740
TI  - [Biocompatibility of micturition alert device dedicated to neurogenic bladder].
AB  - OBJECTIVE: To investigate the biocompatibility of silica gel embedded permanent
      magnets of the micturition alert device dedicated to neurogenic bladder. METHODS:
      According to the national standards of biological evaluation of medical equipment
      (GB/T 16886), Shanghai Biomaterial Research and Test Center was confined to
      evaluate the biocompatibility of silica gel embedded permanent magnets both in
      vitro and in vivo, including cytotoxicity test, sensitization test, primary skin
      irritant test and acute general toxicity test. The cytotoxicity test was
      performed according to the agar diffusion method. The L929 cell discoloration
      index and cell lysis index were counted at 24 hours after the action of the
      specimen. The sensitization test was performed according to the maximal dose
      method. The skin response was evaluated in 30 male albino guinea-pigs at 24 and
      48 hours after the routine induction and provocation of leaching liquors of the
      specimen. The primary skin irritant test was evaluated in 2 male healthy New
      Zealand rabbits according to the local tissue response at 24, 48 and 72 hours
      after intradermal injection of leaching liquors of the specimen. The acute
      general toxicity test was evaluated in 10 male Kunming mice musculus albus
      according to animal condition at 4, 24, 48 and 72 hours after injection of
      leaching liquors of the specimen through the caudal vein. Both the general
      reaction of canines and the pathology of the local bladder walls were observed at
      2, 4 and 8 weeks after a permanent magnet was fixed on the anterior wall of
      urinary bladder in three canines. RESULTS: No sensitization, no stimulation and
      no acute general toxicity were observed except slight cytotoxicity to silica gel
      embedded permanent magnets. After implantation of a permanent magnet, the canines
      showed excellent tolerance, which manifested as no abnormality in spirit,
      appetite, urine and stool, healed wounds and no infection. Adhesions occurred
      between the epiploon and the bladder wall around the permanent magnet in two
      canines at 2 and 4 weeks, and between the lower abdominal wall and the bladder
      wall around the permanent magnet in the other canine at 8 weeks. The local
      bladder wall below permanent magnet was thickened, the fibrous capsule around the
      permanent magnet was thin, but the bladder mucosa was normal. Inflammatory
      reaction such as congestion, edema and inflammatory cells lessened from the
      serosa layer to the mucosa layer microscopically. CONCLUSION: Silica gel embedded
      permanent magnets used in the micturition alert device dedicated to neurogenic
      bladder has excellent biocompatibility and meet the criteria for clinical
      application.

PMID- 18822741
TI  - [Effects of enamel matrix proteins on attachment, proliferation and pre-mRNA of
      type I collagen synthesis of human dermal fibroblast cells in vitro].
AB  - OBJECTIVE: To investigate the influence of enamel matrix proteins (EMPs) on the
      attachment, proliferation and pre-mRNA of type I collagen synthesis of cultured
      human dermal fibroblast cells. METHODS: Human dermal fibroblast cells were
      obtained from human acrobystia and cultured in DMEM medium with 10% FBS. The 3rd
      to 6th passage cells were used. Ninety-six-well plates and 6-well plates were pre
      coated with different concentrations of EMPs (50, 100, 150 and 200 microg/mL).
      (1) The cell attachment experiment: 0.2 mL cells suspension at the concentration
      of 1 x 10(6)/mL was added to the pre-coated 96-well plates as the experimental
      groups (groups A, B, C and D based on different concentrations of EMPs). At 1.5,
      3.0, and 4.5 hours after inoculation, the attached cells were measured by MTT
      method. (2) The cell proliferation experiment: 0.2 mL cells suspension at the
      concentration of 5 x 10(4)/mL was added to the pre-coated 96-well plates as the
      experimental groups (groups A1, B1, C1 and D1 based on the different
      concentrations of EMPs). At 2, 4, 6 and 8 days after inoculation, the cells were
      measured by MTT method. (3) The synthesis experiment of pre-mRNA: 2 mL cells at
      the concentration of 1 x 10(6)/mL was added to the pre-coated 6-well plates as
      the experimental groups (groups A2, B2, C2 and D2 based on different
      concentrations of EMPs). At 5 days after inoculation, the synthesis of pre-mRNA
      was measured by RT-PCR method. Human dermal fibroblast cells were added to the un
      coated plates as the control groups. RESULTS: (1) The cell attachment experiment:
      There were significant differences in attachment cells between the control group,
      group A and the groups B, C and D (P < 0.05). There were no significant
      difference between group A and control group (P < 0.05). (2) The cell
      proliferation experiment: At 2 days, there were no significant differences in
      absorbance between the control group and the experimental groups (P > 0.05); at 4
      days and 6 days, the absorbance of groups B1 (0.598 +/- 0.020 and 0.639 +/- 0.016
      ), C1 (0.582 +/- 0.017 and 0.641 +/- 0.020) and D1 (0.574 +/- 0.021 and 0.635 +/-
      0.021) was significantly higher than that of the control group (0.548 +/- 0.021
      and 0.605 +/- 0.019, P < 0.05); at 8 days, the absorbance of group B1 (0.629 +/-
      0.012) and group C1 (0.631 +/- 0.014) was significantly higher than that of the
      control group (0.606 +/- 0.031, P < 0.05). (3) The synthesis experiment of pre
      mRNA: The synthesis of type I collage pre-mRNA of groups B2, C2 and D2 was
      significantly higher than that of the control group. CONCLUSION: EMPs stimulate
      human dermal fibroblast cell attachment, proliferation and synthesis of type I
      collage pre-mRNA, and its maximal effect can be achieved at the concentration of
      100 microg/mL.

PMID- 18822742
TI  - [Study on differentiation of embryonic stem cells into osteoblast in vitro
      inducing by 1,25(OH)2VD3].
AB  - OBJECTIVE: To investigate the effect of 1,25(OH)2VD3 on differentiation of
      embryonic stem cells (ESCs) into osteoblasts. METHODS: Osteoblasts were isolated
      and cultured from calvarium of 2-day-old Kunming white mice, embryoid bodies
      (EBs) were prepared with modified zur Nieden method. EBs were divided into 4
      groups according to different mediums: group A, as the control group, in which
      EBs medium contained no leukemia inhibitory factor; group B, in which EBs medium
      contained supplements of Vitamin C (VC, 50 microg/mL) and beta-glycerophosphate
      (beta-GP, 50 mmol/L); group C, in which EBs medium was the same as that of group
      B and 5 x 10(4) osteoblasts of 3rd passage were seeded into each well; group D,
      in which the medium contained supplements of VC (50 microg/mL), beta-GP (50
      mmol/L) and 1,25(OH)2VD3 (4 x 10(-9) mol/L), and 5 x 10(4) osteoblasts of 3rd
      passage were seeded into each well. The ALP activity was determined by ALP
      reagent kit every 5 days. The RQ-PCR was performed to measure the mRNA
      expressions of osteocalcin (OCN). Alizarin red S staining was performed to count
      the bone nodules. RESULTS: The expression of ALP witnessed no obvious change in
      each group within 5 days after adherence of EBs, but increased gradually after 5
      days. The expression of ALP in group D reached the peak at 20 days. Red nodules
      with clear outline and different sizes were evident by microscope. Alizarin red S
      staining testified the number of bone nodules in groups A, B, C and D was 20 +/-
      8, 18 +/- 5, 31 +/- 1 and 50 +/- 1, respectively, indicating significant
      differences between groups C, D and groups A, B (P < 0.05), no significant
      difference between group A and group B (P > 0.05), and a significant difference
      between group C and group D (P < 0.05). The result of RQ-PCR showed that the mRNA
      expressions of OCN in groups A, B, C and D was 10.18 +/- 1.17, 20.29 +/- 1.03,
      18.84 +/- 4.07 and 32.15 +/- 5.23, respectively, indicating significant
      differences between groups C, D and groups A, B (P < 0.05), no significant
      difference between group A and group B (P > 0.05), and a significant difference
      between group C and group D (P < 0.05). CONCLUSION: The combined action of
      1,25(OH)2VD3 (4 x 10(-9) mol/L), VC, and beta-GP can effectively promote the
      differentiation of the ESCs-derived osteoblasts.

PMID- 18822743
TI  - [Experimental study on biological feature of rabbit intervertebral disc nucleus
      pulposus in vitro].
AB  - OBJECTIVE: To research the biological feature of intervertebral disc nucleus
      pulposus cells (NPCs) by observing cell amorphous, phenotype and
      ultramicrostructure. METHODS: The NPCs from 2-week-old healthy rabbit were
      cultured in DMEM/F12 medium with 15% FBS. The cell biological features were
      observed by inverted phase contrast microscope, light microscope, electron
      microscope, cell vitality assay, cell growth curve and cells staining after
      harvest and during the periods of culturing the primary, the 1st passage and 2nd
      passage. RESULTS: The results of inverted phase contrast microscope showed that
      the primary passage adhered at 5 days, grew exponentially at 6-8 days, and were
      subcultured after covering the bottom at 17 days. The phenotype of the NPCs
      changed from polygon to long fusiform with passage increased; the vitality assay
      showed that there was about 95%-97%, 98%-100%, 100% and 75%-80% NPCs survived
      just after isolation from intervertebral disc, during the period of culturing the
      primary, the 1st passage and the 2nd passage, respectively. The toluidine blue
      staining of the NPCs was strongly positive, and HE staining showed clear cell
      nucleus and cytoplasm. The I collagen immunohistochemical staining showed
      negative results in the 1st passage, but II collagen immunohistochemical staining
      and safranin O staining showed positive results. However, the I collagen
      immunohistochemical staining showed positive result in the 2nd passage, and II
      collagen immunohistochemical staining and safranin O staining showed weakly
      positive results. The cell growth curve showed the same as the growth course of
      cell cultured in vitro. The results of TEM showed that there were many glycogen
      particles and less chondriosomes in the primary passage. With the increased
      passage, the glycogen particles decreased and the chondriosomes increased, and
      cell organ became swell. CONCLUSION: This study clarifies the biological feature
      of NPCs in vitro, providing the experimental basis for the seed cell research of
      the nucleus pulposus tissue.

PMID- 18822744
TI  - [Experimental study on ultra-filtration in reducing matrix effects of
      recombination human acellular dermal matrix immersion on residual bovine serum
      albumin measurement by ELISA].
AB  - OBJECTIVE: To investigate the effect of ultra-filtration on reducing the matrix
      effects of the immersion of recombination human acellular dermal matrix (rhADM)
      on detecting residual bovine serum albumin (BSA) by ELISA. METHODS: Preparation
      of rhADM immersion: rhADM were rinsed, and then rhADM immersion were prepared.
      Physiological saline was used as immersion medium. Presaturation and ultra
      filtration: marked the ultra-filtration tubes as PR1 (presaturation protocol 1),
      PR2 (presaturation protocol 2) and rhADM, respectively, added 2 mL of 1 mg/mL and
      10 microg/mL BSA solution into PR1 and PR2 respectively, and added 2 mL of rhADM
      immersion into rhADM tubes (rhADM1 and rhADM2). The tubes were then centrifuged
      at 1500 x g for 20 minutes. The above steps were repeated for 3 times. Take the
      inner-tube of ultra-filtration into unused centrifuge tube. Added 4 mL of 10
      microg/mL BSA solution in PR1 and PR2 tubes, 4 mL of rhADM immersion in rhADM
      tubes, centrifuged at 1500 x g for 20 minutes, and then the filtration was
      collected. Detecting BSA concentration: the BSA concentrations of all samples
      were detected by using the quantitative measure of residual BSA ELISA kit. The
      recoveries of 10 microg/mL BSA solution treated by presaturation protocol 1 and 2
      were calculated (untreated 10 microg/mL BSA solution was as the basic sample,
      marked R10 and R20 respectively). The correlation coefficient between the
      logarithm of the filtrate dilution and the absorbance (A) value was calculated
      and compared with that of water exact without ultra-filtration. RESULTS: The BSA
      concentration of PR1 and R10 was (23.80 +/- 1.58) microg/mL and (9.04 +/- 0.24)
      microg/mL, respectively. The BSA concentration of PR2 and R20 was (8.64 +/- 0.24)
      microg/mL and (8.12 +/- 1.01) microg/mL, respectively. The average recovery of 10
      microg/mL BSA was 263.4% +/- 16.9% and 106.5% +/- 3.0% when the ultra-filtration
      tubes were presaturaed by PR1 and PR2 (P < 0.01), respectively. The BSA recovery
      of PR2 met the detecting demand. The correlations between A value and sample
      dilution were increased, the correlation coefficient was raised from -0.727 to 
      0.960 after rhADM immersion were treated by ultra-filtration. CONCLUSION: The
      results show that the matrix effects can be reduced effectively by ultra
      filtration, indicating that an acceptable recovery of BSA can be acquired when
      ultra-filtration tube is presaturated by sample water extract.

PMID- 18822745
TI  - [Research advancement of bone marrow derived stem cell heterogeneity and its role
      in intestinal epithelial repair].
AB  - OBJECTIVE: To summarize and review the heterogeneity of bone marrow derived stem
      cells (BMDSCs) and its formation mechanism and significance, and to analyze the
      possible roles and mechanisms in intestinal epithelial reconstruction. METHODS:
      The related literature about BMDSCs heterogeneity and its role in intestinal
      epithelial repair was reviewed and analyzed. RESULTS: The heterogeneity of BMDSCs
      provided better explanations for its multi-potency. The probable mechanisms of
      BMDSCs to repair intestinal epithelium included direct implantation into
      intestinal epithelium, fusion between BMDSCs and intestinal stem cells, and
      promotion of injury microcirculation reconstruction. CONCLUSION: BMDSCs have a
      bright future in gastrointestinal injury caused by inflammatory bowl disease and
      regeneration.

PMID- 18822747
TI  - The dynamics of research in nursing.

PMID- 18822746
TI  - [Research progress in cardiac biological pacemaker created by cell
      transplantation].
AB  - OBJECTIVE: To review the current status and problems in developing cardiac
      biological pacemaker (CBP) by cell transplantation. METHODS: The literature over
      the past decade concerning CBP constructed through cell transplantation was
      reviewed and summarized. RESULTS: Experiments in vivo testified that the cell
      transplantation was feasible for CBP construction, and the transplantation of
      sinus atrial node cell and stem cell was still the predominant method for
      constructing CBP. However, such problems as difficult amplification of
      transferred cardio muscle cell, low success rate of CBP construction as well as
      unstable function of CBP make it lag behind the tremendous clinical demands. The
      gene transfection technology might be one of the approaches to resolve these
      issues. CONCLUSION: As one feasible method for CBP construction, the cell
      transplantation has a bright future in the clinical application and is worthy of
      further study.

PMID- 18822748
TI  - [The postpartum appointment: women's needs from the perspective of social needs
      in health care].
AB  - Postpartum appointments are essential in women health care. This study aimed at
      identifying the social health needs of women during postpartum. A survey was
      conducted with 50 puerperal women of the Curitiba Mother Program receiving care
      at basic health units of a health district of the city of Curitiba, Parana,
      southern Brazil. An instrument with objective questions was applied in February
      and March, 2007, to collect the data. Descriptive statistics was used to analyze
      the data. The most frequently mentioned set of needs was "to be someone with the
      right to be different", whereas the least mentioned was "link with health
      professional and team". The latter appears as a positive aspect of the nurse's
      (and health team) work, whereas the first shows the need to build practices to
      strengthen the autonomy and the self-reliance of women in health care.

PMID- 18822749
TI  - [The clinical and social vulnerability of children with special healthcare
      needs].
AB  - Children with special healthcare needs (CSHCN) require increasing care by
      relatives and health services. Due to the 'invisibility' of this group, a
      qualitative studied was carried out to analyze and to discuss the dimension of
      physical care provided to CSHCN. The studied included the analyses of the
      patients' records, interviews of family caretakers in a university hospital in
      southern Brazil, and the application of a sensitive creative method. Findings
      showed that these children are clinically and socially vulnerable. Consequently,
      during home care, their caretakersf'ce challenges related to care complexity and
      to the fact of being women. The presence of the State is scarce, and follow-up
      nursing after discharge is absent. It is recommended that these caretakers are
      taught some nursing knowledge, and that actions are taken to improve prenatal
      care services as a preventive measure.

PMID- 18822750
TI  - [Death and dying in the nurse formation process].
AB  - Death is one of the great mysteries of life. We live in a death denying-society.
      This aim of the present qualitative study was to see if undergraduate Nursing
      students are prepared to face death and dying during training. Seven students
      enrolled in the discipline "Supervised Training II", the last discipline of the
      course were interviewed using a semi-structured script, and the collected data
      were submitted to content analysis. The following categories were discussed:
      facing death in daily life, reaction to death, and dying in training. It was
      observed that the process of death and dying is not approached in a manner that
      supplies the students' needs in routine situations that require them to provide
      dying patients humane conditions to die.

PMID- 18822751
TI  - [Burns and the family experience as to the hospitalization process].
AB  - Hospital admission due to burning is usually fast and unpredictable. There may be
      different reactions to trauma according to the phase experienced by the patient
      and his/her family. This study aimed at describing the impact of the
      hospitalization of burnt patients on family dynamics. The Calgary Family
      Assessment Model was applied using semi-structured interviews and direct
      observation of family members. The following phases were considered for data
      analysis: reading the material and data reduction, data presentation, conclusion
      presentation, and verification. The findings showed that family members
      experience a crisis period that affects their physical and emotional status,
      relationships, daily routine, management of financial resources, and work. All of
      these aspects change the family dynamics, contributing for the maintenance of a
      crisis-adjustment-stability cycle during the entire treatment

PMID- 18822752
TI  - [Knowledge on chronic oral anticoagulation of patients followed up in a
      specialized outpatient clinic].
AB  - This study was carried out to assess patients' knowledge on anticoagulant therapy
      in an outpatient clinic. A questionnaire with ten questions with closed answers
      was applied. Correct answers to about 80% of the questions were considered
      satisfactory. Out of the 120 evaluated patients, 77 (64.1%) showed satisfactory
      knowledge, with an average of 7.8 +/- 1.7 correct answers. As to the
      International Normalized Ratio (INR), 69.4% of the sample was beyond therapeutic
      range, and 42.5% had hemorrhages in the last 6 months. Factors such as education
      level, income, hemorrhagic event, anticoagulation time, and gender did not show
      statistically significant difference. There is an obvious need for a systematic
      follow-up by health care professionals, using educational measures, to detect the
      difficulties faced by patients, maintaining an optimal INR.

PMID- 18822753
TI  - [The experience of elderly submitted to complete laryngectomy].
AB  - Laryngectomy causes functional and esthetic lesions on the patients, and
      therefore they need emotional support to resume their activities. This
      exploratory descriptive study, with a qualitative approach, was developed with 16
      elderly patients of Rio Grande do Sul, Brazil, submitted to complete
      laryngectomy, with the aim of collecting their experience after the surgery. Data
      were collected using semi-structured interviews. The thematic analysis allowed
      building the following categories possible to be built: identity loss, social
      isolation, and communication dfficulties. The change in body image and
      communication difficulties contribute for the elderly perception of social
      exclusion, being a burden to the family, and concern with the future. Limitations
      resulting from surgery and from changes in body image result in emotional and
      social fragility, which can be minimized by the support of interdisciplinary
      interventions.

PMID- 18822754
TI  - [Flow and use of health services: medium complexity users' mobility].
AB  - The organization of health services must respond to population demands resulting
      from complex social, individual and cultural factors. The objective of this study
      was to build the social-economic and demographic profile of the users to
      illustrate how to intermediate-complexity health services are used by mapping
      user flows in the southern region of the state of Rio Grande do Sul, Brazil. This
      was a descriptive and transversal study with 150 users. Statistic and spatial
      analyses were used. User flow analysis revealed dissonance between the
      Regionalization Master Health Plan and users' practice because the organization
      proposed by the State does not correspond to users' real needs of moving in the
      local space. An inevitable political engagement is evidenced on behalf of
      regionalization, and users' mobility and building therapeutic trajectories were
      considered as new challenges to be faced by public health.

PMID- 18822755
TI  - [Activity-based management applied in an intensive care unit of a public
      hospital].
AB  - This quantitative study proposed to apply Activity-Based Management in an
      Intensive Care Unit (ICU) of a teaching hospital Porto Alegre, Rio Grande do Sul,
      Brazil. The objective of applying that tool was to direct the establishment of
      strategies, aiming at reducing costs and optimizing human, technological, and
      financial resources used in intensive care. The process of patient admission in
      the ICU was the focus of the analysis. Data were collected in sir collective
      interviews with 13 ICU team members. The results showed that Activity-Based
      Management can be used in an ICU, replicated, and that understanding the care
      process helps to provide information that aid the management to make decision, to
      identify the need of improvement, and to include the team members in the ICU
      management practice.

PMID- 18822756
TI  - [The access to the prenatal assistance in the basic health care from the
      perspective of pregnant women].
AB  - This qualitative study was conducted with the aim of analyzing the access to
      prenatal care at the Basic Health Care Program under the perspective of pregnant
      women who were attended to at a Basic Health Unit in Porto Alegre, Rio Grande do
      Sul, Brazil. Data were collected using semi-structured interviews. Transcription
      and thematic analysis of the interviews gave rise to five analytical
      categories:forms of access to prenatal service; obstacles to begin and/or to
      continue care; access to multiprofessional care; access to reference systems; and
      access to Health Education activities. The results suggest that some aspects of
      that service should be adapted to provide the real needs of women who use it and
      to strengthen the links with the professionals working in that unit.

PMID- 18822757
TI  - [Shift reporting: a strategic resource for the continuity of nursing care].
AB  - Shift reporting is an important tool for organizing and planning nursing care.
      The purpose of this study was to describe how shift reporting is conducted in
      some wards of a teaching hospital in Porto Alegre, Rio Grande do Sul, Brazil, and
      to identify the nurses' knowledge on how to systematize this activity. Two data
      collection methods were used in this qualitative study: observation of shift
      report; and a questionnaire answered by nurses. Data were submitted to thematic
      content analysis. In all wards, shift report happened during a nurses' meeting,
      when information was exchanged, although nurse knew other form of shift
      reporting. Several positive and negative factors affect shift reporting, and the
      nursing staff should try to make this activity as easy, systematic, and effective
      as possible.

PMID- 18822758
TI  - [The relationship between the family member and the child with AIDS:
      understanding in the light of Martin Buber].
AB  - This qualitative study with a phenomenological approach aimed at understanding
      what it means to be a family caregiver of a child living with the Acquired
      Immunodeficiency Syndrome (AIDS) in the light of Martin Buber's philosophy. The
      study was carried out at the Pediatric outpatient Unit of a teaching hospital of
      Porto Alegre, Rio Grande do Sul, Brazil with the participation of 7 family
      caregivers. Data was collected between September and October, 2006 using
      phenomenological interviews, and interpreted using Ricouer's hermeneutics. The
      ethical issues were considered. Being a family member of a child with AIDS is a
      complex existential phenomenon including changes, caring, dialogues, and concerns
      in search of the wellbeing of both children and caretaker in the world.
      Understanding the meaning of these phenomena the life of these families is
      essential to Nursing in order to plan and to develop a humanistic, ethical,
      esthetical, and solidary care.

PMID- 18822759
TI  - [Reorganization of services: challenges of the psychiatric reform].
AB  - This qualitative study, based on social survey, aimed at understanding actions
      carried out in mental health in nine cities of the 10th Health District of the
      Health Care Module of Cascavel, Parana, Brazil. Nine municipal health secretaries
      participated in a semi-structured interview carried out between July and
      September, 2004. Collective Subject Discourse (CSD) was used to analyze the data.
      Five CSD and three meaning-generating themes (service reorganization, home
      visits, and prevention) were identified. The present article discusses theme 1-
      service reorganization, which should include diverse mental health care modes
      integrated to the regional basic health care network.

PMID- 18822760
TI  - [Patient satisfaction in a laboratory test collection unit].
AB  - This exploratory descriptive study aimed at identifying customer satisfaction
      attributes in the field of laboratory tests. Data were collected in 2006, using
      104 interviews in a laboratorial unit inside a teaching hospital, using the
      critical incident technique, and submitted to content analysis. Three attribute
      categories were identified: time spent in waiting for care, interpersonal
      contact, and technical skills. These results subsidize the assessment of the
      current satisfaction survey tool, and point to its reformulation. They also allow
      the identification of improvement needs in customer attention, and provide
      elements to be taken into account in personnel selection, training programs,
      personnel performance assessment.

PMID- 18822761
TI  - [Nursing supervision: a management tool].
AB  - Supervision is a management tool in the nurse's working context. This qualitative
      exploratory-descriptive study aimed at understanding how the work routine of
      nurses in supervisory positions is organized. Data were collected by semi
      structured interviews with five subjects working at Hospital de Clinicas de Porto
      Alegre, Rio Grande do Sul, Brazil, and submitted to content analysis.
      Supervisors' work demand increased due to their administrative tasks, requiring
      more attention when prioritizing actions. Subjects also believed face-to-face
      contact with the nursing team extremely important to manage routine nursing
      tasks. This study also makes some contributions as to the supervisor's profile,
      and some reflections his/her tasks.

PMID- 18822762
TI  - [Family experience on the care needs relative to insulin therapy and diabetic
      foot prevention].
AB  - This study aimed at describing routine insulin therapy and lower-limb lesion
      prevention practices used by relatives of diabetes mellitus patients. Semi
      structured interviews were carried out at home, and 38 families of the municipal
      district of Bandeirantes, Parana, Brazil, were included. Results revealed that
      relatives had good knowledge on glycemic control and diabetic foot prevention,
      particularly of non-medication care, with emphasis on food. Insulin therapy care
      is very demanding for relatives, both in emotional and technical terms. It was
      concluded that the quality of the relationship among family members, encouraging
      the patient to comply with insulin therapy and special diet, and concern with
      food items available at home are essential for the patient with diabetes
      mellitus.

PMID- 18822763
TI  - [Intravenous insulin: controversy on the adsorption process of infusion kits].
AB  - Insulin adsorption is a non-specific surface phenomenon that interferes with the
      patient's insulin demand. This literature review aimed at identifying the causes
      of insulin adsorption in intravenous solutions and the strategies used to reduce
      adsorption. Articles from Medical Literature and Retrieval System On Line
      (MEDLINE), Latin American and Caribbean Health Science Literature (LILACS),
      Cumulative Index to Nursing & Allied Health Literature (CINAHL) and Co-ordination
      and Improvement of Graduate People (CAPES) databases were used. Polypropylene
      flasks and in-line equipment without filter presented less adsorption, adsorption
      was maximum when the first looml of the solution were infused. Strategies used to
      minimize insulin adsorption pre-exposure of 50 to 100 solution flasks for 30-60
      minutes, use of flasks with smaller internal surface, and short in-lines.

PMID- 18822764
TI  - [Pain similarities and differences in the chest syndromes: systematic literature
      review].
AB  - Clinical conditions that present chest pain should be its causes quickly and
      precisely diagnosed. The objective of this study was to identify the existence of
      specific and common pain characteristics in acute myocardial infarction, angina,
      pericarditis, dissected thoracic aorta, and esophagus conditions. A systematic
      literature search was carried out using descriptors related to pain and chest
      syndromes. The following databases were searched for articles published between
      1996 and November, 2005: Caribbean and Latin American in Health Sciences
      Literature (LILACS), Medical Literature and Retrieval System On Line (MEDLINE),
      Nursing Database (BDEnf), Pan-American Health Organization Database (PAHO), World
      Health Organization Library Database (WHOLIS), and Cochrane Library, between 1966
      and November of 2005. No conclusive studies on the characterization of chest pain
      diagnosis were found.

PMID- 18822765
TI  - [Pain assessment and analgesia in pre-admission care of trauma patients].
AB  - Pain is one of the main complaints at admission in emergency services. This
      article aims at presenting pain assessment methods in trauma patients using
      objective tools in pre- and intra-hospital settings. The harmful effects of pain
      in the post-trauma patients, and the benefits of early analgesia are discussed.
      We found that acute pain in emergency wards is rarely studied in Brazil, which
      points out a significant gap in terms of care and research.

PMID- 18822766
TI  - [The integrated curriculum in nursing undergraduate training: between the
      traditional and the disruptive ethos].
AB  - The contemporary world reveals new needs to society, stimulating the universities
      to search ways to understand these demands and to train people to supply them.
      This article discusses Nursing undergraduate studies,focusing on an integrated
      curriculum as a novel instrument that allows the faculty and the students to
      analyze problems from the perspective of other areas of knowledge beyond those
      taken by the regular disciplines. The importance of an integrated curriculum is
      highlighted as a mechanism to socially share knowledge using flexible pedagogical
      tools that take into consideration new models of society, stressing the
      differences between the traditional and disruptive ethos.

PMID- 18822767
TI  - [Sexuality and hysterectomy: myths and reality].
AB  - Hysterectomy is a surgical procedure that may interfere with women's sexual
      sensations and expression. Sexuality may have different meanings. Women submitted
      to hysterectomy may experience situations that disturb their identity as women.
      Therefore, reflections must be made on those influences on sexuality. Ideas on
      gender and sexuality are used in this article to explain concepts and to relate
      them to the possibilities of nursing care based on changing the dominant
      paradigm.

PMID- 18822768
TI  - [Fungal phytotoxins: from basic studies to practical use (a review)].
AB  - Recent materials are summarized, pertaining to classification of fungal
      phytotoxins, methods of their isolation, and assays for biological activity.
      Producers of phytotoxic substances have been characterized, and the chemical
      nature of phytotoxins has been subjected to analysis. The review gives
      consideration to the mechanisms of action of phytotoxins on susceptible plants
      and the mechanisms of plant resistance to such agents. Other matters discussed
      include prospects of utilizing basic knowledge of the nature and mechanisms of
      action of phytotoxins for developing means of plant protection against diseases
      and weeds and identifying or classifying fungi (chemosystematics).

PMID- 18822769
TI  - [Thymidine and thymidylate kinases from the scallop Mizuhopecten yessoensis
      gonads].
AB  - Thymidine and thymidylate kinases were isolated from the gonads of scallop
      Mizuhopecten yessoensis. The enzymes were purified 537- and 100-fold,
      respectively, and were free of phosphatase and ATPase impurities. Ions of
      bivalent metals and ATP were necessary for both the nucleoside and nucleotide
      kinase activities; the pH optimum fall into the range of 7.5-8.5. KCl and NaCl at
      a concentration of up to 100 mM had no inhibiting effect on the activities of
      these scallop enzymes. Thymidine kinase catalyzed thymidine, and, at a lower
      rate, deoxycytidine phosphorylations did not utilize ribo- and
      deoxyribonucleosides, as well as pyrimidine ribonucleosides, as a phosphate
      acceptor. Thymidylate kinase phosphorylated TMP and dCMP with an efficiency of
      about 30%. In addition to ATP, these enzymes can also utilize with different
      efficiencies dATP, dGTP, GTP, UTP, and CTP as a donor of phosphate groups.
      Thymidine kinase activity was inhibited by TMP, TTP, and dCTP.

PMID- 18822770
TI  - [Isolation and characteristics of new thermostable DNA ligase from archaea of the
      genus Thermococcus].
AB  - The DNA ligase gene from thermophilic archaea of the genus Thermococcus (strain
      1519) was identified and sequenced in the polymerase chain reaction. The
      recombinant enzyme LigTh1519 was expressed in Escherichia coli, purified, and
      characterized. LigTh1519 was capable of ligating the cohesive ends and single
      strand breaks in double-stranded DNA (ATP as a cofactor). The optimum conditions
      for the ligase reaction appeared as follows: 100 mM NaCl, 50 mM MgCl2, pH 7.0
      10.5, and temperature 70 degrees C. More than 50% Lig1519 activity were preserved
      after incubation of the enzyme at 80 degrees C for 30 min. New thermostable DNA
      ligase LihTh1519 may be used for basic and applied researches in molecular
      biology and genetic engineering.

PMID- 18822771
TI  - Examination of bovine lactoferrin binding to bifidobacteria.
AB  - In the present study, lactoferrin binding to bifidobacteria and detection of
      lactoferrin-binding protein in membrane fractions of several bifidobacteria have
      been demonstrated. This is the first report showing the binding of bovine
      lactoferrin to four Bifidobacterium spp. (B. infantis, B. breve, B. bifidum, B.
      longum) incubated with biotinylated lactoferrin and fluorescein conjugated-avidin
      and observed under an inverted confocal laser scanning microscope. Fluorescence
      staining showed lactoferrin binding at the pole of the bacterial cells. A
      lactoferrin-binding protein with a molecular weight of approximately 67 kDa was
      also detected in the membrane fraction of Bifidobacterium spp. by far western
      blotting technique using biotinylated lactoferrin and horseradish peroxidase
      conjugated streptavidin. Based on the results of this and previously reported
      studies, we suggest that binding of lactoferrin to Bifidobacterium longum is
      strain-dependent.

PMID- 18822772
TI  - [Effect of growth conditions on the molecular weight of poly-3-hydroxybutyrate
      produced by Azotobacter chroococcum 7B].
AB  - It has been shown that poly-3-hydroxybutyrate (PHB) of predetermined molecular
      weight can be obtained by varying the growth conditions of the producer strain,
      Azotobacter chroococcum 7B: pH, temperature, aeration, presence of sodium acetate
      as an additional carbon source, or growth on crude complex carbon sources
      (molasses, vinasse, or starch). High-molecular-weight polymer can be obtained at
      pH 7.0, optimal for the culture (1485 kDa), temperature 30-37 degrees C (1600
      1450 kDa, respectively), and low aeration (2215 kDa). The following factors
      decrease PHB MW: pH deviation to the acidic (pH 6.0, 476 kDa) or alkaline (pH
      8.0, 354 kDa) range or lower temperature (20 degrees C, 897 kDa). Introduction of
      additional carbon source (sodium acetate) at concentrations in the medium varying
      from 0 to 5 g/l provides an original method of production of PHB with
      predetermined MW in a wide range, from 270 to 1515 kDa, with high PHB content in
      the cell.

PMID- 18822773
TI  - Effect of bioprocess conditions on growth and alkaline protease production by
      halotolerant Bacillus licheniformis BA17.
AB  - The effect of bioprocess conditions (pH and temperature) on the growth and
      alkaline protease production of halotolerant Bacillus licheniformis BA17
      bioreactor cultures have been systematically analyzed using response surface
      methodology in order to assess the importance of these generally disregarded
      parameters. Two models were proposed differing by the choice of response
      variable. Under optimized bioprocess conditions, whole alkaline protease activity
      was about 3 fold higher than the activities obtained in the preliminary studies.
      Results of this study not only highlight the importance of pH and temperature for
      further engineering purposes but also serve as basis for understanding the true
      mechanism lying under the relation between these process parameters and growth
      and whole alkaline protease production.

PMID- 18822774
TI  - [Sequential degradation of p-cresol by photochemical and biological methods].
AB  - Sequential photo- and biodegradation of p-cresol was studied using a mercury
      lamp, as well as KrCl and XeCl excilamps. Preirradiation of p-cresol at a
      concentration of 10(-4) M did not affect the rate of its subsequent
      biodegradation. An increase in the concentration of p-cresol to 10(-3) M and in
      the duration preliminary UV irradiation inhibited subsequent biodegradation.
      Biodegradation of p-cresol was accompanied by the formation of a product with a
      fluorescence maximum at 365 nm (lambdaex 280 nm), and photodegradation yielded a
      compound fluorescing at 400 nm (lambdaex 330 nm). Sequential UV and
      biodegradation led to the appearance of bands in the fluorescence spectra that
      were ascribed to p-cresol and its photolysis products. It was shown that
      sequential use of biological and photochemical degradation results in degradation
      of not only the initial toxicant but also the metabolites formed during its
      biodegradation.

PMID- 18822775
TI  - [Isolation of an aboriginal bacterial community capable of utilizing cyanide,
      thiocyanate, and ammonia from metallurgical plant wastewater].
AB  - An aboriginal bacterial community capable of degrading cyanide (10 mg/l) and
      thiocyanate (2 g/l) and eliminating ammonia (120 mg/l) had been isolated from
      recycled water samples after blast-furnace gas purification of a metallurgical
      plant wastewater. It was shown that the optimal conditions for this bacterial
      community were as follows: temperature, 34 degrees C; pH, 8.8-9.0; available
      organic matter concentration (glucose equivalent), 5 g/l; and dissolved O2
      concentration, 8-10 mg/l. This aboriginal community was formed by the bacteria
      belonging to the genus Pseudomonas.

PMID- 18822776
TI  - [Effect of acidic treatment of the chemical composition and bacterial oxidation
      of arsenic-bearing gold concentrate].
AB  - Effect of acidic pretreatment of arsenic-bearing gold concentrate, a promising
      gold source, on its chemical composition and efficiency of its bacterial
      oxidation (BO) was studied. The titer of sulfobacilli during BO of the
      concentrate after high-temperature acidic treatment was 9.0 x 10(7) cells/ml, the
      degree of arsenic sulfide oxidation being 71.1%, and in the control, 6.5 x 10(7)
      cells/ml with the oxidation degree as low as 48.7%. Deeper oxidation of the main
      gold-containing mineral, arsenic sulfide, would allow more efficient gold
      recovery from the concentrate.

PMID- 18822777
TI  - [Kinetic aspects of inhibition of the phytopathogenic fungi growth by rhizospera
      bacteria].
AB  - Kinetics of growth inhibition of fungi Fusarium and Bipolaris caused by bacteria
      Pseudomonas sp. V-6798 and Azotobacter chroococum V-2272 D on dense nutrient
      media, both in single-crop system and by coinoculation, was demonstrated. The
      speed of fungal colonies growth as a function of bacteria concentration in
      inoculate was shown to be in accordance with the Ierysalimskii modified equation.
      The degree of antagonistic activity was suggested to be assessed by the constant
      of inhibition (Ki) and residual rate of fungi growth. Constant of inhibition of
      fungal growth by bacteria varied within 10-100 cells/ml for observed species.
      More effective fungistatic influence of bacterial strains in combined culture was
      observed. Parameters reported in the present study allow comparing the degree of
      bacteria antifungal activity in vitro. Suggested screening method could be used
      for selection of bacteria as activity biofungicide and while selecting
      biomedication for defined plant pathogen disruption.

PMID- 18822778
TI  - [Regulatory effect of microbial alkyloxybenzenes of different structure on the
      stress response of yeast].
AB  - The effect of alkyloxybenzenes (AHBs) belonging to the class of alkylresorcinols
      differing in the degree of hydrophobicity--C7-AHB and more hydrophobic Cl12-AHB-
      on the resistance of Saccharomyces cerevisiae cells to heat shock and oxidative
      stress of lethal intensity was studied. Depending on structure and concentration,
      AHB added 2 h before exposure to stress had either an antistress or stress
      potentiating effect on yeast cells in the mid-logarithmic growth phase. C7-AHB at
      concentrations 0.25-0.5 g/l caused a two- to fivefold increase in the resistance
      of yeast cells to hydrogen peroxide (30-150 mM), whereas Cl2-AHB reduced it at
      all concentrations. C7-AHB and Cl2-AHB had a similar effect on yeast subjected to
      heat shock (45 degrees C, 30 min). It was found that the degree of the protective
      effect of C7-AHB and potentiating effect of Cl2-AHB depended on the nature of the
      stressor, being more pronounced in heat shock. The environmental significance of
      the antistress and stress-potentiating effects of microbial AHBs is discussed.

PMID- 18822779
TI  - [Lipids of filamentous fungi as a material for producing biodiesel fuel].
AB  - Species of various filamentous fungus taxa were tested for ability to produce
      lipids suitable as a material for manufacturing biodiesel. The mucoralean fungus
      Cunninghamella japonica was found to be a promising lipid producer. The
      inexpensive medium for its growth developed in this study contained ammonium
      nitrate as a nitrogen source. With its use, up to 16 g/l biomass and over 7 g/l
      lipids was obtained. The fungal lipids were dominated by oleic acid. It
      constituted 50% of total fatty acids. The iodine index of the lipid fraction was
      86.61. The heat of combustion of the lipids, 37.13 MJ/kg, was close to the value
      for rapeseed oil.

PMID- 18822780
TI  - [Increased secretion of lignolytic enzymes by the Lentinus tigrinus fungus after
      addition of butanol and toluene in submerged cultivation].
AB  - We studied the effects of butanol and toluene on secretion of lignolytic enzymes
      by the Lentinus tigrinus fungus during submerged cultivation. Addition of butanol
      and toluene during the trophophase was followed by an increase in laccase and
      peroxidase activity of the culture and change in the composition of phospholipids
      and fatty acids. The ratio of phosphatidylcholine and phosphatidic acid
      decreased, while the amount of lysophosphatidylcholine, phosphatidylethanolamine,
      phosphoinositides, phosphatidylserine, and unsaturated fatty acids decreased.
      These changes resulted in an increase in the unsaturation index.

PMID- 18822781
TI  - [Primary and secondary metabolism of winter wheat under cold hardening and
      treatment with antioxidants].
AB  - The content of saccharides and phenolic compounds (including flavonoids and
      lignin) and the activity of L-phenylalanine ammonia-lyase (PAL, EC 4.3.1.5) were
      determined in leaves and tillering nodes of winter wheat Triticum aestivum L.)
      cultivars Inna and Moskovskaya 39, differing in the level of frost resistance.
      These parameters were determined in three groups of plants--control, hardened,
      and treated with synthetic antioxidants (ambiol and amerol 2000). Cold hardening
      increased accumulation of primary and secondary metabolites in tissues but
      decreased the enzyme activity. Treatment with antioxidants also increased the
      content of saccharides and phenolic compounds (primarily flavonoids) and PAL
      activity. These changes were more pronounced in cultivar Inna, which is less
      frost resistant than Moskovskaya 39.

PMID- 18822782
TI  - [Immunochemical properties of conjugated antigens from N-substituted
      phenothiazines and dibenzazepines with antiarrhythmic activity].
AB  - The use of metabolites of antiarrhythmic drugs (ethmozine, ethacizine, and
      bonnecor) as haptens in the synthesis of conjugated antigens allowed us to induce
      the formation of antibodies with different specificity for certain metabolites. A
      new enzyme immunoassay was developed for the detection of phenothiazine and
      dibenzazepine derivatives (ethmozine, ethacizine, and bonnecor). Nanogram and
      subnanogram quantities of these substances may be detected in biological fluids.

PMID- 18822783
TI  - [The influence of starter cultures on the formation of volatile compounds in dry
      smoked sausages].
AB  - The differences between the composition of volatile substances in two specimens
      of dry smoked sausages produced using a standard and experimental (a mixture of
      propionic acid bacteria and bifidobacteria) cultures were studied by capillary
      gas chromatography. It was found that the experimental starter culture
      intensified the flavor-formation processes as compared with the standard culture.
      The experimental specimen had richer qualitative and quantitative compositions
      and displayed more intensive aroma and flavor. The contents of lactones and
      volatile terpenoids in the experimental specimen were much higher than in the
      control. The organoleptic characteristics of experimental dry smoked sausage
      specimen were considerably better.

PMID- 18822784
TI  - [Obtaining and study of monosaccharide derivatives of low-molecular-weight
      chitosan].
AB  - The possibility of obtaining monosaccharide derivatives of low-molecular-weight
      chitosan with the use of the Maillard reaction was studied. Chitosan derivatives
      (molecular weight, 24 and 5 kDa) obtained with glucosamine, N-acetyl
      galactosamine, galactose, and mannose with a substitution degree of 4-14% and a
      yield of 60-80% were obtained. Some physicochemical and biological properties of
      these derivatives were studied. We showed that monosaccharide derivatives of low
      molecular-weight chitosan exhibited antibacterial activity. Chitosan at a
      concentration of 0.01% caused 100% death of bacteria B. subtilis and E. coil. The
      strongest antibacterial effect was exhibited by 24-kDa derivatives: only 0.02
      0.08% of cells survived. These derivatives were two orders of magnitude more
      effective than the 5-kDa chitosan modified with galactose.

PMID- 18822785
TI  - [Regulation of the life span in unicellular eukaryotes].
AB  - The review considers the mechanisms of nucleic and mitochondrial control of the
      life span of unicellular eukaryotes. Special attention is given to analysis of
      the mechanisms of functioning of telomerase complex, the mechanisms of varied
      expression of the genes regulating the cell cycle, and the mitochondrial
      retrograde pathway.

PMID- 18822786
TI  - [Posttranslation regulation of programmable cell events in unicellular
      eukaryotes].
AB  - The review considers the up to date achievements about posttranslational
      regulation of programmable cell events: growth, development, and apoptosis in
      unicellular eukaryotes mediated by histone modifications and DNA metylation.
      Special attention is given to the evolution aspects of the problem.

PMID- 18822787
TI  - [Nucleolus transformation in oocytes of mouse antral follicles. Revealing of
      coilin and RNA polymerase I complex components].
AB  - This study is the continuation of our previous investigation of the nucleolus
      transformation in growing oocytes from mouse multilayer follicles (Pochukalina,
      Parfenov, 2006). Here in the present research we have examined the features of
      organization and molecular composition of nucleolus like body, or postnucleolus,
      in two groups of oocytes with different chromatin configuration from mouse antral
      follicles. Using light and electron immunocytochemistry, we have defined the
      dynamics of ribosomal RNA synthesis and processing molecular component
      distribution in postnucleolus. Considerable changes in RNA polymerase I
      distribution and its colocalization with coilin at the periphery of postnucleolus
      were revealed. Putative role of coilin in formation of complexes with ribosomal
      RNA synthesis/processing components is discussed.

PMID- 18822788
TI  - [Dynamics of the annulate lamellae in Drosophila syncytial embryos].
AB  - In eukaryotic cells, mitotic events are controlled by evolutionarily conserved
      cyclin-dependent kinases (cdk): these kinases phosphorylate cell proteins, which
      causes structural reorganization of the entire cell. Our recent studies of
      Drosophila syncytial embryos have demonstrated that cdk1 activity is a key factor
      that controls nuclear pore complex assembly/disassembly and affects the structure
      of cytoplasmic pores in the annulate. In this paper, we report a comparative
      analysis of these cytoplasmic organelles throughout the cell-cycle and throughout
      the development of Drosophila syncytial embryos. Based on the results obtained,
      it was presupposed that distribution of annulate lamellae containing cytoplasmic
      pores could reflect the inactivation of the mitotic kinase cdk1 in Drosophila
      syncytial embryos.

PMID- 18822789
TI  - [Proteoglycans of L6J1 myoblast extracellular matrix. Characteristics and effect
      on myoblast adhesion].
AB  - Proteoglycans were isolated from extracellular matrix of L6J1 rat myoblasts and
      their influence on myoblast adhesion was studied. Proteoglycan digestion with
      chondroitinase AC and heparinase III degrading the polysaccharide moieties
      revealed that chondroitin sulfate proteoglycans are the main class of myoblast
      extracellular matrix proteoglycans. Electrophoresis of enzymatically processed
      proteoglycans was used to examine their core proteins. Myoblast adhesion was
      suppressed by proteoglycans or the mixture of proteoglycans and
      fibronectin/extracellular matrix. When being processed with chondroitinase AC the
      combined substrate of fibronectin and proteoglycans lost the capability of
      myoblast adhesion suppression. Thus, as a result of presented work the
      proteoglycans of L6J1 rat myoblast extracellular matrix were isolated and
      purified. The main class of proteoglycans was chondroitin sulphate proteoglycans.
      Isolated proteoglycans suppressed myoblast adhesion and this effect was mediated
      by polysaccharide moieties of proteoglycans.

PMID- 18822790
TI  - [Dynamics of ultrastructure changes in sheet plate fiber flax with braking
      transport assimilate by nitrate-anion].
AB  - Changes in leaf mesophyll cell ultrastructure under nitrate feeding into the
      apoplast of common flax (Linum usitatissimum L.) in the form of 50 mM KNO3
      solution were studied. In 30 min after the beginning of nitrate feeding through
      the transpiration water stream, swelling of mitochondrial and microbodies,
      clarification of their matrices, and curling of dictyosome discs into annular
      structures were observed. These events characterized symplastic domain formed by
      mesophyll, bundle sheath and phloem parenchyma cells, and were not found in
      companion cell-sieve element complex. Simultaneously, formation of large central
      vacuoles in companion cells was noted. Restoration of organelle structures in
      assimilating cells and phloem parenchyma in 1-2 h after treatment was accompanied
      by enhancement of morphological changes in phloem elements and companion cells
      and signs of plasmolysis in the mesophyll cells. It was supposed that the two
      phase character of changes in leaf organelle ultrastructure and photosynthesis
      might reflect duality of leaf cell response to nitrate ion. The rapid alterations
      of the structure can be coupled with direct influence of the anion on cell
      metabolism and(or) with signal-regulatory functions of oxidized nitrogen forms,
      while the slower ones reflect the result of suppression of photoassimilate export
      from leaves by the anion.

PMID- 18822791
TI  - [Fate of parental mitochondria in embryonic stem hybrid cells].
AB  - When hybrid cells are created, not only nuclear genomes of parental cells unite
      but their cytoplasm as well. Mitochondrial DNA (mtDNA) is a convenient marker of
      cytoplasm allowing one to gain insight into the organization of hybrid cell
      cytoplasm. We analyzed the parental mtDNAs in hybrid cells resulting from fusion
      of Mus musculus embryonic stem (ES) cells with splenocytes and fetal fibroblasts
      of DD/c mice or with splenocytes of M. caroli. Identification of the parental
      mtDNAs in hybrid cells was based on polymorphism among the parental mtDNAs for
      certain restrictases. We found that intra- and inter-specific ES cell-splenocyte
      hybrid cells lost entirely or partially mtDNA derived from the somatic partner,
      whereas ES cell-fibroblast hybrids retained mtDNAs from both parents in similar
      ratios with a slight bias. The lost of the "somatic" mitochondria by Es
      splenocyte hybrids implies non-random segregation of the parental mitochondria as
      supported by a computer simulation of genetic drift. In contrast, ES cell
      fibroblast hybrids show bilateral random segregation of the parental mitochondria
      judging from analysis of mtDNA in single cells. Preferential segregation of
      "somatic" mitochondria does not depend on the differences in sequences of the
      parental mtDNAs but depends on replicative state of the parental cells.

PMID- 18822792
TI  - [Histological and histochemical characteristics of pancreas of deer at the
      Altay].
AB  - Season changes in the pancreas from animals belonging to genuine deer subfamily
      have been investigated by histological, histochemical and biometric methods.
      Glycogen is not found in the pancreas cells throughout the seasons pointing to
      high functional activity of glandular cells, since glycogen is consumed for
      carbohydrate biopolymer synthesis and not accumulated. Depending upon the season,
      cytoplasm of pancreacells, cells of excretory ducts and pancreas islets showed
      different intensity of pyroninophilous reaction indicating RNA presence. These
      data coupled with the presence of protein in these cells demonstrate protein
      synthesizing ability of the gland adapted to biorhythm. Changes in quantity and
      types of web cells as well as in functional activity of pancrea cells and
      pancreas islets revealed season regularity and reflected functional lability of
      the cells and their constant involvement in many of vital important process.

PMID- 18822793
TI  - [Polymorphism of yellow locus in Drosophila melanogaster from natural
      populations].
AB  - We studied molecular characteristics of yellow (y; 1-0.0) locus, which determines
      the body coloration of phenotypically wild-type and mutant alleles isolated from
      geographically distant populations of Drosophila melanogaster in different years.
      According to Southern data, restrictions map of yellow locus of all studied
      strains differ from each other as well as from that of Oregon stock. FISH
      analysis shows that in the neighborhood of yellow locus in X chromosome neither P
      nor hobo elements are found in y1-775 stock, while only hobo is found there in y1
      859 and y1-866 stocks, only P element in y+sn849 stock, and both elements in y1
      719 stock. Thus, all studied mutant variants of yellow are of independent origin.
      Yellow locus residing at the very end of X chromosome (region 1A5-8 of cytologic
      map) carries significantly more transposon than retrotransposon-induced
      mutations, as compared to white locus (regions 3C2). It is possible that
      transposons are more active than retrotransposons at the chromosomal ends of D.
      melanogaster.

PMID- 18822794
TI  - [The rhythms of daily mitotic activity in Vigna radiata (L.) R. Wilczek].
AB  - The daily mitotic activity (MA) in Vigna radiata (L.) R. Wilczek. has been
      studied using local cultivar for Vietnam No I 176. It has been shown that the
      curve of mitotic activity has five peaks. Maximum mitotic index (MI) was observed
      at 04:00 (5.93 %) and the other peaks were at 02:00 (5.58 %), 08:00 (4.70 %),
      12:00 (4.60 %) and at 22:00 (4.60 %). If we took into account that duration of
      the mitotic cycle in Vigna radiata makes up ten hours, we can propose that there
      are two peaks of MA within each cycle. It may be due to the presence of two
      meristematic cell subpopulations which enter mitosis at different time and have
      nearly equal duration of the cell cycle.

PMID- 18822795
TI  - [Interaction of signal cascades induced by cAMP and prolactin in bovine oocyte
      cumulus complexes].
AB  - Prolactin (PRL) is one of the pituitary hormones participating in the control of
      mammalian folliculo- and oogenesis. In the present study, the joint effect of PRL
      (50 ng/ml) and dibutyryl cAMP (dbcAMP, 1 mM) on oocyte maturation and the
      morphologic-functional state of surrounding cumulus cells was investigated in
      vitro. It has been shown that PRL totally suppresses the braking impact of dbcAMP
      on meiosis reinitiation and the completion of oocyte nuclear maturation.
      Furthermore, PRL partly inhibited cumulus expansion induced by dbcAMP, although
      it exerted the opposite effect in the control medium. In the presence of PRL, the
      inhibitory impact of dbcAMP on the proliferative activity of cumulus cells and on
      the PRL-elicited braking of destructive processes in the cells has been found. In
      cumulus cells, mRNA expression of PRL receptor long isoform was revealed by the
      RT-PCR method. The data obtained suggest an interaction of signal cascades
      induced by PRL and cAMP in bovine oocyte-cumulus complexes, with the coupling
      site of these cascades in oocytes being apparently different from that in cumulus
      cells.

PMID- 18822796
TI  - Paradoxical experience of hypnotic analgesia in low hypnotizable fibromyalgic
      patients.
AB  - The study investigated the differences in pain perception in highly (Highs) and
      low (Lows) hypnotizable patients with chronic benign pain undergoing hypnotic
      suggestions of analgesia. Self reports of pain intensity were collected in
      different groups of fibromyalgic patients: (1) Highs and Lows during pre
      hypnosis, neutral hypnosis, suggestions for analgesia, posthypnotic conditions;
      (2) Lows during suggestions for analgesia administered after a mental stress
      instead of neutral hypnosis; (3) healthy Lows receiving nociceptive stimulation
      during hypnotic relaxation and suggestions of analgesia. The results showed that
      Highs and Lows differed in their response to suggestions, but significant
      analgesia was reported also by Lows. These individuals did not report any
      difference in pain perception between the sessions including mental stress and
      hypnotic relaxation. No change in pain perception was observed in healthy Lows
      during nociceptive stimulation associated with relaxation and suggestions for
      analgesia. In conclusion, the presence of chronic pain seems to be responsible
      for the paradoxical response of non hypnotizable patients to hypnotic
      suggestions.

PMID- 18822797
TI  - Spatiotemporal dynamics of single-letter reading: a combined ERP-FMRI study.
AB  - This work investigates the neural correlates of single-letter reading by
      combining event-related potentials (ERPs) and functional magnetic resonance
      imaging (fMRI), thus exploiting their complementary spatiotemporal resolutions.
      Three externally-paced reading tasks were administered with an event-related
      design: passive observation of letters and symbols and active reading aloud of
      letters. ERP and fMRI data were separately recorded from 8 healthy adults during
      the same experimental conditions. Due to the presence of artifacts in the EEG
      signals, two subjects were discarded from further analysis. Independent Component
      Analysis was applied to ERPs, after dimensionality reduction by Principal
      Component Analysis: some independent components were clearly related to specific
      reading functions and the associated current density distributions in the brain
      were estimated with Low Resolution Electromagnetic Tomography Analysis method
      (LORETA). The impulse hemodynamic response function was modeled as a linear
      combination of linear B-spline functions and fMRI statistical analysis was
      performed by multiple linear regression. fMRI and LORETA maps were superimposed
      in order to identify the overlapping activations and the activated regions
      specifically revealed by each modality. The results showed the existence of
      neuronal networks functionally specific for letter processing and for explicit
      verbal-motor articulation, including the temporo-parietal and frontal regions.
      Overlap between fMRI and LORETA results was observed in the inferior temporal
      middle occipital gyrus, suggesting that this area has a crucial and
      multifunctional role for linguistic and reading processes, likely because its
      spatial location and strong interconnection with the main visual and auditory
      sensory systems may have favored its specialization in grapheme-phoneme matching.

PMID- 18822798
TI  - D-glucose induces microtubular changes in C1300 neuroblastoma cell line through
      the incorporation of 3-nitro-L-tyrosine into tubulin.
AB  - The microtubular network of neurons is involved in several functions such as
      formation and tropism of cellular processes, cell division and intracellular
      transport. A lot of evidences testify that the microtubular network of neurons
      can be impaired by oxidative stress. A condition of oxidative stress is often
      possible when D-glucose overloads its metabolic pathway, resulting in an increase
      in reactive oxygen species and subsequent neurological disorders. The aim of this
      work was to check in undifferentiated mouse neuroblastoma cells (C1300) the
      possible oxidative effects of D-glucose on microtubules. Using a concentration of
      110mM D-glucose, cell morphology, growth rate, viability and catalase activity
      were seriously altered. Noteworthy, an increase in 3-nitro-L-tyrosine and a
      downregulation of tubulins was found in D-glucose-exposed cells, whereas another
      cytoskeletal proteins, namely actin, did not show any changes. In conclusion,
      microtubular network can be impaired by D-glucose through specific nitrosative
      effects, suggesting a possible mechanism at the basis of hyperglycemia-induced
      neuronal damage.

PMID- 18822799
TI  - Orientation sensitive properties of visually driven neurons in extrastriate area
      21a of cat cortex.
AB  - Orientation sensitive properties of extrastriate area 21a neurons were
      investigated. Special attention was paid to the qualitative characteristics of
      neuron responses to the different orientations of visual stimulus motion across
      neuron classical receptive fields (CRF). The results of experiments have shown
      that a group of neurons (31%) in area 21a with specialized responses to moving
      visual stimuli changed their direction selective (DS) characteristics depending
      on the orientation of the stimulus movement. Some neurons reveal an abrupt drop
      of the direction sensitivity index (DI) to certain orientation (58%), and some
      show significant increase of DI at one of applied orientations of stimulus motion
      (22%). Detailed investigation of response patterns of non-directional neurons to
      different orientations of stimulus motion have revealed clear-cut qualitative
      differences, such as different regularities in the distribution of inter-peak
      inhibitory intervals in the response pattern in dependence of the orientation of
      stimulus motion. The investigation of neuron CRF stationary functional
      organization did not reveal correlations between RF's spatial functional
      organization, and that of qualitative modulations of neuron response patterns. A
      suggestion was put forward, that visual information central processing of
      orientation discrimination is a complex integrative process that includes
      quantitative as well as qualitative transformations of neuron activity.

PMID- 18822800
TI  - Tomorrow's stethoscope.

PMID- 18822801
TI  - New law could improve consumer confidence in genetic testing.

PMID- 18822802
TI  - Renewed focus on prevention and wellness in state Medicaid programs.

PMID- 18822803
TI  - Genetically speaking.

PMID- 18822804
TI  - Early intervention. Childhood obesity programs aim to put kids on a new,
      healthier path to adulthood.

PMID- 18822805
TI  - First, communicate.

PMID- 18822806
TI  - The new world.

PMID- 18822807
TI  - Team green. What is good for the environment is good for business--and members,
      too.

PMID- 18822808
TI  - Survey results renew public interest in advance care planning.

PMID- 18822809
TI  - Dental consultants champion evidence-based dentistry.

PMID- 18822810
TI  - Volunteerism is the lifeblood of SOHN.

PMID- 18822811
TI  - Creating a medical home for the child with recurrent respiratory papillomatosis.
AB  - Juvenile onset recurrent respiratory papillomatosis is a chronic disease of the
      pediatric airway caused by human papillomavirus. This paper discusses the
      etiology, epidemiology, symptomatology, diagnosis, and treatment of this disease.
      The role of the pediatric nurse practitioner is described in applying the medical
      home model. Comprehensive primary care is described for children with recurrent
      respiratory papillomatosis, including well child care, episodic illness
      management, and care coordination.

PMID- 18822812
TI  - Project management skills prove invaluable.
AB  - IHEEM business development manager Louise Corfield examines the role of project
      management in the skill set of today's healthcare estates and facilities manager,
      and explains how the Institute has joined forces with a number of organisations
      to offer members access to training in this increasingly vital area.

PMID- 18822813
TI  - Maritime hospital on crest of a wave.
AB  - Kent's Medway NHS Foundation Trust has recently signed up to the Chartered
      Institution of Building Services Engineers' (CIBSE's) 2008 "100 Hours of Carbon
      Clean Up" campaign, encouraged to participate for the third year running by its
      environmental team's winning of a top award in 2007. Health Estate Journal editor
      Jonathan Baillie visited the Trust's sizeable main hospital, Gillingham's Medway
      Maritime, where two of the team described this year's ambitious energy-saving
      plans.

PMID- 18822814
TI  - Planning for the unforeseen.
AB  - Ensuring business continuity in the face of an emergency is arguably more
      important in a healthcare facility, where lives depend on, for example, vital
      medical equipment continuing to function at all times, than in any other
      environment. IHEEM business development manager Louise Corfield examines the
      importance of effective resilience and emergency planning for the healthcare
      estate and highlights the key priorities.

PMID- 18822815
TI  - Flexible design should be primary goal.
AB  - At "Rebuilding the NHS", a recent Health Service Journal conference in London,
      Daryl Murphy, a partner at leading architect and health planning specialist for
      the primary and community care sectors Murphy Philipps, explained how the
      Department of Health's (DH's) forthcoming HBN 11-01 Health Building Note sets out
      a "less prescriptive approach" to the design of new primary care and community
      healthcare facilities.

PMID- 18822816
TI  - Concordat encourages 'measured approach'.
AB  - Simon Greenfield, estates advisor, NHS London, reports on the Fire Safety
      Concordat between the London Fire and Emergency Planning Authority (LFEPA), the
      Department of Health and NHS London, a voluntary agreement aimed at improving
      fire safety in the capital's NHS properties, and discusses the responsibilities
      of NHS hospitals and other healthcare facilities more widely in complying with
      The Regulatory Reform (Fire Safety) Order.

PMID- 18822817
TI  - Building design links to infection control.
AB  - The extent to which a hospital's built environment, ward and clinical layout, and
      the clinical procedures deployed, are directly linked to hospital-acquired
      infection rates, and how existing experience and studies can be best harnessed
      when designing new healthcare facilities, are examined by Graeme Gidney, an
      associate director at Buro Happold.

PMID- 18822818
TI  - Turning up the heat on energy performance.
AB  - Chris Holme, principal engineer, Gateway Review and Estates and Facilities
      Division, Department of Health (DH), discusses what a new requirement for those
      running large publicly-owned buildings to display, publicly, information on their
      site's energy consumption will mean for the NHS when it comes into force on 1
      October.

PMID- 18822819
TI  - New thinking for the boiler room.
AB  - Wayne Rose, marketing manager at integrated plant room manufacturer Armstrong
      Integrated Systems, explains how increasing use of off-site manufacture, the
      latest 3D modelling technology, and advances in control technology, are
      revolutionising boiler room design and construction.

PMID- 18822820
TI  - Primary care services shift proving its value.
AB  - Speaking at "Rebuilding the NHS", a conference recently staged by Health Service
      Journal, John Pope, in his capacity as Department of Health (DH) programme lead,
      New Models of Care, examined how innovative estates planning can "continue to
      facilitate the shift of more health services to primary and community care
      settings". Health Estate Journal reports.

PMID- 18822821
TI  - Portable units help old stager keep cool.
AB  - Heating, ventilating and air conditioning specialist Andrews Sykes' expertise has
      seen comfortable ward temperatures maintained for patients and a good working
      environment ensured for clinical staff at part of an ageing, yet characterful
      19th Century Bristol hospital where structural constraints made installing fixed
      air conditioning impractical. Health Estate Journal reports.

PMID- 18822822
TI  - Pre-planning does a power of good.
AB  - Power quality is a serious, and often costly, issue in healthcare, especially
      when equipment is prone to fail without warning. Powervar's Rob Morris considers
      how sensitive medical equipment can be effectively protected against power
      surges, spikes, electrical noise and large value transients so as to maximise the
      chances of it keeping operating efficiently.

PMID- 18822823
TI  - Distance no object for teleconsultations.
AB  - Cisco's Internet Business Solutions Group (IBSG) is piloting a remote
      teleconsultation system that combines video, audio and medical technology with IP
      telephony to create a "consulting room" environment in a medical setting, home,
      office or shopping mall. Two key goals are to enable patients many miles from
      their nearest doctor to receive remote consultations, and to reduce pressure in
      hospital emergency departments. Jonathan Baillie reports.

PMID- 18822824
TI  - Kilkenny theatres set for top performance.
AB  - Adrian Parkin, operations director at Howorth Air Technology, describes how, in
      May, Ireland's Aut Even Hospital near Kilkenny became the country's first
      healthcare facility to be fitted out exclusively with UCV (ultra-clean
      ventilated) operating theatres, guaranteeing that patients' operations take place
      in the cleanest air possible.

PMID- 18822825
TI  - Sealants fight back aginst bacteria.
AB  - Mike Moran, business development manager, Industrial Construction, at Bostik,
      explains how a range of new sealants increase protection in hospital bathrooms,
      shower rooms and kitchen facilities against healthcare-acquired infections.

PMID- 18822826
TI  - Adolescent attention-deficit/hyperactivity disorder and learning disorders.
      Preface.

PMID- 18822827
TI  - Overview of epidemiology, clinical features, genetics, neurobiology, and
      prognosis of adolescent attention-deficit/hyperactivity disorder.
AB  - ADHD is a common neurobehavioral disorder that is highly heritable. Recent
      research has identified several genes that are associated with ADHD. In addition,
      there are several biological factors that are environmentally derived that appear
      to play a role in the etiology of ADHD. It is quite clear that ADHD begins in
      childhood, but persists into adolescence and adulthood for the majority of
      individuals. Since the criteria for the diagnosis of ADHD are most applicable to
      children, making the diagnosis in adolescents requires an understanding of how
      these symptoms are expressed in this age group. The prognosis of ADHD is variable
      and depends on several psychosocial factors, with approximately 20% of
      adolescents who perform well in social, emotional, and educational domains,
      another 20% who perform poorly in these domains, and the majority who perform
      somewhere in the middle.

PMID- 18822828
TI  - Common comorbidities seen in adolescents with attention-deficit/hyperactivity
      disorder.
AB  - This article provides an overview of key research on significant comorbidities
      that occur among adolescents with attention-deficit/hyperactivity disorder,
      including disruptive behaviors. Such comorbidities include oppositional defiant
      disorder and conduct disorder, as well as depressive disorders, anxiety
      disorders, personality disorders, suicidality, eating disorders, sleep disorders,
      learning disabilities, Internet "addiction," tic disorders, new-onset pediatric
      epilepsy, and celiac disease.

PMID- 18822829
TI  - Learning disorders in adolescence: the role of the primary care physician.
AB  - Adolescents with learning disorders are at significantly increased risk for
      negative outcomes in regard to their emotional, behavioral, and academic
      functioning. Primary care physicians should be alert to the effect of
      neurodevelopmental dysfunctions that might be taking their toll as academic
      demands increase or as new manifestations of previously identified problems
      emerge. The physician should review emotional, family, and environmental factors
      and rule out underlying or associated medical causes and can participate in the
      assessment process. He or she can advise and assist parents with obtaining
      necessary evaluations through the school or by referral to independent clinicians
      and should assist with the interpretation of the findings, ensuring appropriate
      understanding of the challenges by the adolescent and parents and coordinating
      care if other medical specialists are involved. The physician can direct students
      and their families to appropriate resources in the community and advocate for
      appropriate educational services at school. Brief office-based counseling can
      help in dealing with the stresses associated with learning challenges and
      ensuring that students are afforded regular opportunities to pursue their
      affinities and build on their strengths.

PMID- 18822830
TI  - Substance use disorders in adolescents with attention-deficit/hyperactivity
      disorder.
AB  - Attention-deficit/hyperactivity disorder and substance use disorders are commonly
      observed together, particularly in clinical populations of adolescents. The co
      occurrence of these problems is common and presents challenges for the clinician
      in assessment and management. This article will review the extent of the problem,
      the relationship in terms of risk and prognosis, and management issues, including
      the use of stimulant and nonstimulant medications and the risk of abuse, misuse,
      and diversion.

PMID- 18822831
TI  - Medications for adolescents with attention-deficit/hyperactivity disorder.
AB  - ADHD is recognized as a neurologic condition rather than just bad behavior.
      Medical treatment has been recognized as very helpful. Risks of untreated ADHD
      are substantial. Every life area is negatively affected including school
      performance, drug abuse and dependence risk, driving performance, sexually
      transmitted diseases, unwanted pregnancy and family cohesiveness to mention some
      of them. Frequent misinformation in the popular media causes apprehension about
      medical treatment. Even after almost 60 years stimulants remain the mainstay in
      treatment of ADHD. Newer release systems have produced longer acting and smoother
      acting medication. Side effects have always been brief and mild however, newer
      forms cause fewer side effects than older preparations and cover symptoms for
      more of the waking hours of each day. Although studies in adolescents are less
      numerous than in children the literature standard supports the safety and
      efficacy of stimulants in adolescents. In addition there are non-stimulant
      medications that have shown efficacy in adolescents. There are now a greater
      number of medications and more effective medications than ever before. Clinical
      pearls in medication management are shared in practical terms so that these newer
      treatments can be used to help those affected with ADHD more effectively than
      ever before.

PMID- 18822832
TI  - Family intervention for home-based problems of adolescents with attention
      deficit/hyperactivity disorder.
AB  - Adolescents with ADHD frequently argue with their parents about a variety of
      issues, especially when they also have Oppositional Defiant Disorder or Conduct
      Disorder. Family interventions have proven effective for ameliorating such
      conflicts in two independent investigations. After a comprehensive assessment
      including family interviews and self-report inventories, the therapist first
      teaches the parents contingency management techniques and then teaches the
      parents and adolescent problem solving communication skills. Contingency
      management techniques include one-on-one time, effective commands, positive
      incentive systems, and punishment systems. Problem solving involves discussing a
      specific dispute by defining the problem, generating a list of solutions,
      evaluating the solutions, and reaching a compromise. Communication training
      involves identifying specific negative communication skills and replacing them
      with positive communication skills. This article reviews research and provides
      practitioners with specific guidelines for implementing these family
      interventions.

PMID- 18822833
TI  - Social competence and friendship formation in adolescents with attention
      deficit/hyperactivity disorder.
AB  - Friendship formation (making friends, keeping friends, and having successful
      interactions with peers and adults) constitutes a critical developmental-social
      milestone for adolescents. This process can be especially challenging for
      adolescents with attention-deficit/hyperactivity disorder, whose attentional
      problems may negatively affect their social skills (verbal and nonverbal
      language) and who fail to appreciate the complexity and nuances of adolescent
      communication. They often do not respond to feedback cues. They may be perceived
      as "immature," lacking empathy, and loners and losers, they may endure a
      "reputational bias," and they often experience coexisting challenges (eg,
      language problems, learning disabilities, or obesity). Successful and gratifying
      interactions, or the lack thereof, deeply and broadly affect adolescents: their
      self-esteem, self-image, confidence, school-learning, lifestyle, behavior, sexual
      activity, intimacy formation, mental-emotional well-being, and physical health.
      Successful achievement of this ever-evolving milestone has lifelong implications.
      This article describes various social-interactional skills, other components of
      social competence, and the dysfunctions that may cause social failure and
      suffering and describes how to evaluate and help manage problems in adolescents
      with attention-deficit/hyperactivity disorder.

PMID- 18822834
TI  - School-based interventions for adolescents with attention-deficit/hyperactivity
      disorder.
AB  - Adolescents with attention-deficit/hyperactivity disorder (ADHD) frequently
      encounter significant difficulties with academic, behavioral, and social
      functioning in secondary school settings. Although psychotropic medication (eg,
      stimulants) may reduce ADHD symptoms, this treatment does not directly address
      functional impairments. Four broad psychosocial treatment classes including
      behavioral, academic, self-management, and multimodal intervention programs have
      been used to address the school difficulties adolescents with ADHD. Relevant
      research supporting each of these treatment approaches is described along with
      the clinical implications of these findings. Limitations of the extant literature
      are identified in order to delineate critical directions for future treatment,
      development and research.

PMID- 18822835
TI  - Attention-deficit/hyperactivity disorder and complementary/alternative medicine.
AB  - The use of complementary and alternative medicine (CAM) for treatment of
      attention-deficit/hyperactivity disorder (ADHD) has increased both by parents and
      health care providers. Despite scientific evidence supporting the effectiveness
      of stimulants in the treatment of ADHD, the use of stimulants has received
      negative publicity and, for many parents, is worrisome. Concerns regarding
      adverse effects and the prospect of long-term use of pharmacologic treatments
      make many parents uncomfortable thus they seek "alternative treatments." With the
      information explosion produced by the Internet, marketing for alternative
      therapies such as herbal remedies, elimination diets, and food supplements for
      ADHD has increased. Many people use CAM because they are attracted to the CAM
      philosophies and health beliefs, dissatisfied with the process or results of
      conventional treatments, or concerned about adverse effects of stimulants.
      Although some scientific evidence exists regarding some CAM therapies, for most
      there are key questions regarding safety and efficacy of these treatments in
      children. The aim of this article is to provide a general overview and focus on
      the evidence-based studies of CAM modalities that are commonly used for ADHD.

PMID- 18822836
TI  - Educational rights of children and adolescents with attention
      deficit/hyperactivity disorder.
AB  - This article describes the evolution of the legal rights of children with
      Attention Deficit Hyperactivity Disorder (ADHD) under the federal special
      education law, the Individuals with Disabilities Education Act, and under the
      federal disability rights law, Section 504 of the Rehabilitation Act of 1973.
      This article highlights key requirements under each law and compares how they
      apply to children with ADHD. The article also identifies key steps that
      physicians can take to assist children with ADHD to obtain appropriate
      educational and related services, accommodations and legal protections under
      these laws.

PMID- 18822837
TI  - Attention-deficit/hyperactivity disorder: a personal perspective.
AB  - Children with ADHD can achieve academic and personal success in adulthood. In
      this article the author shares personal perspectives on his own struggles with
      ADHD as a child and shares insights, tips, and anecdotes from his own life. These
      insights, when viewed in light of the scientific literature regarding ADHD, offer
      new directions for research into the management of the disorder in children and
      adolescents.

PMID- 18822838
TI  - Training medical staff for pediatric disaster victims: a comparison of different
      teaching methods.
AB  - OBJECTIVE: The goal of this study was to assess the effectiveness of the
      different types of healthcare worker training in pediatric disaster medicine
      knowledge over time and to analyze the effects of training type on healthcare
      workers' attitude toward pediatric disaster medicine. DESIGN: Prospective
      randomized controlled longitudinal study. SETTING: Large, urban, tertiary
      academic children's hospital. SUBJECTS: Physicians and nurses employed at
      Children's Hospital Los Angeles randomly selected from a global hospital e-mail
      server over a 3-week time frame were invited to participate and receive an
      incentive on completion. Forty-three controls and 42 intervention subjects (22
      lecture + tabletop exercise, 20 lecture only) completed the study. Subjects with
      disaster training in the prior 6 months were excluded. INTERVENTIONS: Subjects
      underwent a didactic lecture or a combination of didactic lecture and tabletop
      exercise. Preintervention and postintervention testing took place using a 37
      question multiple-choice test on pediatric disaster medical topics. Posttesting
      took place immediately after intervention and then 1, 3, and 6 months after the
      intervention. Subjects also were surveyed before and after intervention regarding
      their attitudes toward pediatric disaster medicine. MAIN OUTCOME MEASURES: (1)
      Scores on a 37-question knowledge test and (2) Likert scores on self-perceptions
      of knowledge, comfort, and interest in pediatric disaster medicine. RESULTS:
      Regardless of intervention type, participant scores on a postintervention
      pediatric disaster medicine tests over a 6-month period increased and remained
      well above pretest means for intervention and control pretest scores. There were
      no differences in scores comparing type of intervention. However, subjects who
      underwent the tabletop simulation had a better sense of knowledge and comfort
      with the topics compared with those who only underwent a didactic lecture.
      CONCLUSIONS: Didactic lecture and tabletop exercises both increase healthcare
      worker's knowledge of pediatric disaster medical topics. This knowledge seems to
      be retained for at least 6 months postintervention. The addition of the tabletop
      exercise to a standard didactic lecture may increase a learner's sense of
      knowledge and comfort with disaster topics, which may in turn lead to increased
      staff participation in the event of an actual disaster.

PMID- 18822839
TI  - Validation of the Short Posttraumatic Stress Disorder Rating Interview (expanded
      version, Sprint-E) as a measure of postdisaster distress and treatment need.
AB  - OBJECTIVE: Professionals and paraprofessionals working in disaster settings need
      tools to identify persons with mental health needs. To validate the Sprint-E as a
      measure of postdisaster distress and treatment need, the authors tested (1) the
      concurrent validity of the measure compared with other measures of distress, (2)
      the sensitivity and specificity of a "3/7 rule" on the Sprint-E relative to
      probable PTSD diagnosis, and (3) the hypothesis that Sprint-E scores would be
      stable in the absence of treatment but would improve in its presence. METHOD: In
      Study 1, data were collected at the point of enrollment from 165 adults
      participating in a Florida treatment program implemented in response to the 2004
      hurricanes. In Study 2, data were collected at points of referral, pretreatment,
      and intermediate treatment from 128 adults participating in a Baton Rouge
      Louisiana treatment program implemented in response to the 2005 hurricanes,
      Katrina and Rita. RESULTS: The utility of a 3/7 rule for the Sprint-E, with 3
      suggesting possible and 7 suggesting probable treatment needs, was supported in
      Study 1. Tested against the PTSD Checklist, the Sprint-E performed well in ROC
      analyses (area under the curve = 0.87); a score of 7 achieved sensitivity of 78
      percent and specificity of 79 percent. In Study 2, Sprint-E scores evidenced
      little change between referral and pretreatment but substantial change between
      pretreatment and intermediate treatment. CONCLUSION: The Sprint-E is useful as an
      assessment and referral tool in situations where more in-depth assessment is not
      feasible and mental health services are available.

PMID- 18822840
TI  - Hazmat disaster preparedness in Hong Kong: what are the hazardous materials on
      Lantau, Lamma, and Hong Kong Islands?
AB  - OBJECTIVE: Hazmat disaster preparedness is critical, especially as Hong Kong
      prepares for major international events, such as the 2008 Olympic Equestrian
      Games. No published medical study describes the identities and quantities of
      hazardous materials (HMs) in Hong Kong and lists what antidotes are needed for
      these dangerous goods (DGs). This study describes what HMs are most common in
      Hong Kong to prioritize disaster preparedness and training. DESIGN: A
      descriptive, cross-sectional study. SETTING: The Hong Kong Special Administrative
      Region, specifically Lantau, Lamma, and Hong Kong Islands. SAMPLE: The Hong Kong
      Fire Services Department (HKFSD) Dangerous Goods Database (DGD). INTERVENTIONS:
      Descriptive statistical analyses with Stata 9.2. MAIN OUTCOME MEASURES:
      Identifying and quantifying HMs in the HKFSD DGD. RESULTS: Most HMs do not have
      antidotes. The most common HMs with recognized antidotes are carbon monoxide,
      methylene chloride, fluorides, cyanides, nitriles, hydrazine, methanol, and
      nitrates. The most common categories of DGs are substances giving off inflammable
      vapors, compressed gases, and corrosive and poisonous substances. CONCLUSIONS:
      Hazmat disaster preparedness and training should emphasize these most common
      categories of DGs. Disaster planning should ensure adequate antidotes for HMs
      with recognized antidotes, ie, oxygen for carbon monoxide and methylene chloride;
      calcium gluconate and calcium chloride for fluorides; hydroxocobalamin or amyl
      nitrite, sodium nitrite, and sodium thiosulfate for cyanides and nitriles;
      pyridoxine for hydrazine; fomepizole or ethanol for methanol; and methylene blue
      for methemoglobinemia produced by nitrates. Supportive care is essential for
      patients exposed to HMs because most DGs do not have antidotes.

PMID- 18822841
TI  - Application of a needs-driven, competencies-based mental health training program
      to a post-disaster situation: the Grenada experience.
AB  - This report outlines an innovative approach to address post-natural disaster
      mental health needs in a region in which natural disasters are common---the
      Caribbean. Instead of traditional external vertical psychosocial interventions
      commonly used in this region, the authors developed and implemented a mental
      health interventions training program, in the island country of Grenada, which is
      focused on enhancing the capacity of local community-based health service
      providers to provide immediate and continued mental healthcare following a
      natural disaster. Soon after this training, a hurricane stuck the island of
      Grenada. A review of the self-confidence in the application of this training and
      the mental health intervention activities of these community health providers
      demonstrated that they felt able to effectively identify, intervene, and address
      post-disaster mental health needs within their communities and that their care of
      individuals affected continued beyond the immediate post-disaster period,
      suggesting that enhancing the capacity of local community-based health providers
      to deal with post-natural disaster mental health needs may be a useful model that
      may be applicable in other jurisdictions.

PMID- 18822842
TI  - Use of ultrasound to assess acute fracture reduction in emergency care settings.
AB  - OBJECTIVE: There is a need to develop tools for the rapid diagnosis and treatment
      of fractures and intraosseous pathology in remote and austere environments.
      Several emergency and orthopedic studies have demonstrated ultrasound to be a
      reliable tool in diagnosing these conditions in both adult and pediatric
      patients. The purpose of this pilot study is to assess the ability of the
      ultrasound to assess in "real-time" the success of fracture reduction in adult
      patients in the emergency department (ED), in comparison with the accepted
      standard, plain film radiography, for the purposes of future application in
      austere environments. DESIGN: Case series. SETTING: Emergency department at an
      academic medical center. PATIENTS/PARTICIPANTS: Convenience sample of five
      patients presenting to an ED with clinical evidence of fractures (three radial,
      one phalangeal, and one metacarpal). INTERVENTIONS: A Sonosite Titan portable
      ultrasound system with L38/10-5:38-mm broadband linear array transducer was used
      to assess prereduction and postreduction angulations and alignment. Alignment was
      reconfirmed with use of fluoroscopy and plain radiography. RESULTS: The
      ultrasound confirmed proper reduction and realignment in all five cases, from an
      average prereduction angle of alignment of 37.4 degrees to an average
      postreduction angle of 4.4 degrees. The use of the ultrasound resulted in
      adequate visualization of the reduction in all cases. Regional anesthesia or
      sedation and limited pressure with the probe resulted in no verbalization of pain
      by any of the subjects. CONCLUSIONS: In this pilot study, emergency physicians
      demonstrated the use of ultrasound in place of traditional radiography to either
      confirm adequate reduction or assess the need for further manipulation. Our pilot
      study suggests that ultrasound has a possible future role in fracture reduction
      management in both the ED as well as "austere"prehospital locations.

PMID- 18822843
TI  - [Medical error, medical secrecy, bioethics: essence and legal aspect].
AB  - The lecture presents questions on essence and legal aspect of medical fault,
      medical secret and bioethics which are the components of protection of a
      physician's and patient's right in health care.

PMID- 18822844
TI  - Chronic morbidity in women, namely in pregnancy. (Comparative study between West,
      Central and East European centres).
AB  - 18 chronic diseases were investigated in a population of 13,115 women living in
      six settings of West- (Avon UK, the Isle of Man), Central- (the Czech Republic
      and the Slovak Republic) and East-Europe (the Ukraine and Russia), that
      collaborate in the European Longitudinal Study of Pregnancy and Childhood (ELSPAC
      project). In prenatal questionnaires filled in after the first half of pregnancy,
      women reported 25,795 chronic diseases they ever suffered, out of them 11,188
      having in present pregnancies. In the whole sample, lifelong prevalence was
      11,2%, and prevalence in pregnancy 4,8% which means that 43,4% of all chronic
      diseases recurred in pregnancy. Up to mean age of 255 years in the whole sample,
      39,6% women reported ever having indigestion, 29% back pains, 22,6% migraine,
      about 16% haemorrhoids, hay fever and eczema, about 10% varicose veins, anorexia
      nervosa, heavy depression and kidney diseases, over 5% rheumatism and 4% asthma.
      Less prevalent were infections of pelvic organs, febrile convulsions, joint
      inflammations, stomach ulcers, psoriasis and epilepsy. Lifetime prevalence of
      chronic diseases and their prevalence in pregnancy were the highest in the
      western zone and decreased eastwards, but recurrence grew in the opposite
      direction, being the highest in the eastern zone. The variation of each morbidity
      indicator is followed in all diseases between geographical zones as well as
      between individual study centres.

PMID- 18822845
TI  - [Pharmacotherapy of patients with chronic heart failure. Analysis of multicenter
      international studies].
AB  - Leterature data and own investigations are summarized in the article. New
      experimental facts about mechanism of action of cardiac glycosides (especially
      digoxin) were obtained last year. It was shown that in human organism there are
      endogenous cardiosteroids (digitalis-like substances, endogenous oubain and
      other). They are in different organs (adrenal glands, hypothalamus, pituitary
      gland) and have influence on different organs and systems. Indications,
      contraindications, side effects, interactions with other drugs have been studied
      by cardiologists. Results of international multicentere studies demonstrate high
      efficacy of digoxin in treatment of chronic heart failure caused by compromised
      contractile activity of myocardium, atrium fibrillation and is used for
      controlling number of heart contractions and supraventricular paroxysmal
      tachycardia. More than 200 years history of scientific researches and clinical
      use of cardiac glycosides show that this group of medicine may be applied in a
      combine pharmacotherapy of chronic heart failure together with antihypertensive
      drugs.

PMID- 18822846
TI  - [Connection of endothelial dysfunction and level of blood leukocytes with
      clinical course of stable angina pectoris in patients with ischemic heart
      disease].
AB  - The authors presents in the article information on influence of endothelial
      dysfunction and level of blood leukocytes with clinical course of stable angina
      pectoris in patients with ischemic heart disease (IHD). 104 male patients aged
      from 36 to 69 (on average 54.9+/-2.1 years) with IHD and stage I-III stable
      angina pectoris have been observed. The level of leukocytes, ECG daily
      monitoring, endotelial function with the help of Celermaera-Sorensena test and
      plasma concentration of endothelin I have been studied in patients. It was
      established that there is no significant different (P>0.05) in the level of
      leukocytes between health persons and patients with IHD independently of
      functional class of angina pectoris. Patients with IHD had higher level of
      endothelin I in their blood serum than those in a control group. Patients with
      IHD have a complicated endothelial-non-dependent vasodilation and an increased
      thickness of the complex intima-media, there is a negative correlation bond
      between these characteristics. Patients III functional class of angina pectoris
      has also reliably decreased endothelial-dependent vasodilation by 37%. Frequency
      of ventricular extrasystoles in patients with IHD and endothelial dysfunction
      increases by 12 times.

PMID- 18822847
TI  - [Short-term prognosis of the course of acute coronary syndrome (according to
      analysis of data of one-channel ECG in phase space and variability of the heart
      rhythm)].
AB  - 74 patients with different variants of coronary syndrome have been observed at
      myocardial infarction department of #5 Kiev sity clinical hospital.
      Investigations showed that 66 (89%) patients from 74 had their symmetry dynamics
      of T wave in phase space correlated with a clinical picture and outcome of the
      treatment carried out in the cardioresuscitation of patients with acute coronary
      syndrome (ACS). Patients with positive results of the treatment of ACS had their
      T-waves decreased, patients who had not improved had their T-waves stable on
      increased. These changes were statistically certain. Changes of symmetry of T
      wave in a phase space have a good correlation with treatment results.

PMID- 18822848
TI  - [Pathogenetic variants of liver steatosis: diagnostic approach using serum lipid
      levels].
AB  - Hepatic steatosis may develop secondary to abnormalities in lipid and/or glucose
      metabolism. We presume that a phenotype of lipid profile may represent
      pathogenetic variant of steatosis. liver steatosis had been diagnosed on
      ultrasonography in 108 patients (27 with alcoholic liver disease, 28 with chronic
      HCV hepatitis and 21 with chronic HBV hepatitis; 34 patients with chronic viral
      hepatitis (CVH) had alcohol abuse). Serum levels of total cholesterol (TC), its
      fractions and triglycerides (TG) were assessed by standard tests. chi2 (chi
      square) criterion was used to assess reliability of the lipid parameters
      deviation, alcohol-induced (AI), virus-induced (VI) and mixed pathogenetic
      variants of liver steatosis had been identified. TC level >200 mg/dL, LDL
      cholesterol >120 mg/dL, TG >150 mg/dL, and normo- or hypoglycemia were typical,
      while TC level<180 mg/dL and hyperglycemia were not found in patients with AI
      steatosis. TC level<180 mg/dL, LDL-cholesterol<100 mg/dL and TG<150 mg/dL were
      typical for VI steatosis. 46,4% of patients with HCV hepatitis and 19% of
      patients with HBV hepatitis had TC level<140 mg/dL and LDL-cholesterol<70 mg/dL.
      In patients with CVH and alcohol abuse a mixed variant of liver steatosis has
      been diagnosed, their serum lipid levels were lower than those in patients with
      alcoholic liver disease, and insignificantly higher than those in patients with
      CVH. Conclusions. Determination of pathogenetic type of steatosis in patients
      with fatty infiltration of the liver is adjunctive to the diagnosis and is a
      screening test for patients with CVH. Serum levels of HDL-cholesterol below
      normal values were frequently seen in patient with III grade steatosis.

PMID- 18822849
TI  - [Induced acute non-lymphoblastic leukemia and prognostic significance of
      cytogenetic abnormalities: trisomy in chromosome 8, inv(16)(p13q22), and
      t(8;21)(q22;q22)].
AB  - 3 patients with secondary acute non-lymphoblastic leucosis have been observed.
      The cytogenetic analysis revealed pathologic karyotypes: 46, XY,+8, t(8;21), inv
      16. Two patients have been found with typical markers of damaged chromosome of
      radiation origion. Insensibility of blastic cells to cytostatic therapy was
      typical for the patients.

PMID- 18822850
TI  - [Experience of two-valve prosthesis in patients with combined aorto-mitral heart
      disease].
AB  - One of the main orientations of cardiosurgery is a surgical treatment of combined
      aortomitral valvular disease and often in combination with mitral valve
      insufficiency. The article presents the authors's surgical experience on
      treatment of patients with combined aortomitral valvular disease. Analysis of
      frequency and patern of complications during hospital stage of treatment and its
      remote results are given by authors in the article.

PMID- 18822851
TI  - [Pneumothermometric estimation of conditioning function of the respiratory system
      in ischemic heart disease].
AB  - The research was carried out on 153 patients with ischemic heart disease at
      standard ambient temperature and humidity. The conditioning function of the
      respiratory system was examined by pneumothermometric method. Values of expired
      air temperature (EAT) have been compared with predicted values. Statistically
      significant increase of EAT was observed: in myocardial infarction - 0.49 degrees
      C, in atherosclerotic cardiosclerosis - 0.36 degrees C, in unstable angina
      pectoris - 0.12 degrees C. These data how respiratory heat exchange flux in
      patients with ischemic heart disease, possibly due to lung haemodynamics
      disturbances which are common among patients with this pathology. This measuring
      of expired air temperature is advisable for functional diagnostics of the
      respiratory system in routine and emergency cases.

PMID- 18822852
TI  - Diagnostic algorithm for identification of individuals with hereditary
      predisposition to breast cancer.
AB  - Breast cancer originates from genetic and environmental factors leading to
      accumulation of mutations in both nuclear DNA (nDNA) and mitochondrial DNA
      (mtDNA). Incidence of breast cancer cases rises dramatically with ageing.
      Approximately 90% of breast cancers are sporadic while the remaining 10% are
      inheritable. BRCA1 and BRCA2 mutations are associated with a greatly increased
      risk for development of hereditary breast cancer (HBC). Besides BRCA mutations,
      enhanced production of ROS and accumulation of mitochondrial DNA mutations in
      mitochondria of post mitotic cells are a contributory factor to human aging. In
      this review, a model for predisposition to HBC incorporating the BRCA mutation,
      mtDNA4977 mutation, ER and TP53 was developed. Our model shows that germ-line
      point BRCA mutations transmitted from ancestors accelerated the somatic oxygen
      damages and mtDNA mutations leading to phenotypic expression of premature aging
      and breast cancer. Also, a diagnostic algorithm targeted at active identification
      of hereditary breast cancer was developed and introduced into clinical practice
      by diagnosis of founder BRCA mutation, mitochondrail common deletion and clinical
      parameters.

PMID- 18822853
TI  - [Biological age of asbestoscement plant workers in Ukraine].
AB  - Biological age of asbestoscement workers was estimated. The accelerated ageing
      was recorded in asbestos cement workers, especially in male groups in comparison
      with female ones. It is established that with the increase of the work experience
      record the biological age decreases. This can be connected with biological
      (difference of adaptation processes in different persons) and social-economic
      factors. The obtained results conform to the availability the accelerated ageing
      among workers engaged in other industries.

PMID- 18822854
TI  - [About phenomenon of time and efficiency of chronotherapy of chronic diseases].
AB  - Resonance chronophytotherapy (RCT) was carried out to patients with epilepsy,
      bronchial asthma, rheumatism, scleroderma, hypertension, chronic
      glomerulonephritis, vegetovascular dystonia, female sterility, round-type
      alopecia, vitiligo, eczema, psoriasis, onychomycosis. Special medicine technology
      RCT does not have any adverse effects nor contraindications and is intended first
      of all to eliminate non specific signs of a disease, decrease dependence and
      complications of applying chemical synthetic medications. RCT may be used
      together with any type of specific treatment. Internet variant of TRC have been
      developed.

PMID- 18822855
TI  - [Efficiency of introduction of the program for quality management of medical care
      of oncological patients].
AB  - The performance indicators of city hospital oncological proctological department
      have been analysed before and after the introduction of the program of quality
      management to medical care. The detailed analysis of indexes with the use of
      methods of variation statistics allowed to confirm positive influence of
      organizational experiment on intensification of the use of bed fund for
      oncological patients and improvement of performance indicators, in particular,
      frequencies of postoperative complications.

PMID- 18822856
TI  - [Creation and cross-cultural adaptation of ukrainian versions of questionnaires
      for assessment of quality of life of children with atopic dermatitis and their
      families].
AB  - Origional versions of the Dermatitis Family Impact, Infant's Dermatitis Quality
      of Life Index and Children's Dermatology Life Quality Index questionnaires have
      been translated into Ukrainian independently by two translators and then back-
      translation was done by other translators. Total number of forward or back
      translation was 6. A final back-translation was approved by one of the authors
      and copyright owner, prof. A.Y. Finlay. The probe technique for pre-testing was
      used. Retest reliability, discriminant validity and over time sensitivity have
      been checked. 60 children with atopic dermatitis received Trixera emollient cream
      for a month that led to decrease of their SCORAD (P<0.01) score and was followed
      by improvement of both health-related and family quality of life (P<0.01). It was
      confirmed high sensitivity of the questionnaires to successful therapeutic
      intervention. Ukrainian versions of the Dermatitis Family Impact, Infant's
      Dermatitis Quality of Life Index and Children's Dermatology Life Quality Index
      questionnaires could be used for practical and research reasons as important
      sources of additional information.

PMID- 18822857
TI  - [Influence of chronic diseases of reserve military personnel of Ukraine army on
      their capability to do their duty according military speciality].
AB  - The author presents in the article the way of distribution of reserve military
      personnel of Ukraine army on special groups depending on presence of chronical
      diseases or pathological conditions. The author analyzed more than 800 personal
      files of military personnel and other materials related to assessment of
      functional state of this personnel and efficiency of performing their duty. Data
      received from Kiev commissariats and other Ukraine military Institutions have
      been analyzed. The proposed way of military personnel distribution allows
      optimizing their operating mode by creating a special mode where resource of
      military personnel's professional health is preserved.

PMID- 18822858
TI  - [N.D. Strazhesko and his role in the development of modern clinical medicine].
AB  - The article presents information on academician N.D.Strazheshko- the founder of
      one of key native therapeutic schools with its new, original features. In the
      article was shown an important contribution of the scientist to the study of
      significant questions related to internal medicine and his role in the
      development of current clinical medicine.

PMID- 18822859
TI  - [Sergei Gavrilovich Navashin: two jubilees].

PMID- 18822860
TI  - [Double fertilization in flowering plants: 1898-2008].
AB  - A short review of the results of investigations in the field of plant embryology
      in vivo and in vitro which are directly connected with the discovery of double
      fertilization in flowering plants by S.G. Navashin is presented. These results
      have been obtained by using the methods of electron and fluorescence microscopy,
      cytophotometry, cultures of isolated ovules, sperms, eggs, and embryo sac central
      cells. The question on an origin of the female gametophyte of flowering plants,
      double fertilization, and endosperm are discussed. It is emphasized that the
      progress in this field is connected mostly with the study of molecular processes
      which control the development and functioning of a female gametophyte and
      sporophyte at the early stages of ontogenesis.

PMID- 18822861
TI  - Monozygotic cleavage polyembryogenesis and conifer tree improvement.
AB  - The mass cloning of elite genotypes of commercially important conifers has led to
      the establishment of an industrial forest of two of the most important softwood
      species in the USA. Embryonal-suspensor masses, produced by monozygotic cleavage
      polyembryony (MCP), are rescued from controlled-pollinated seeds in tree breeding
      orchards. MCP is scaled up as cell suspensions and grown into mature somatic
      embryos. The embryos serve as a source for the production of various artificial
      and manufactured seeds used in replicated field trials to test genotype x
      environmental interactions. For the capture of genetic gains, early selections
      are based on correlations with known traits. This reduces the costs of years of
      tree improvement. Mass cloning and genotype cryopreservation enables field
      testing under a wider range of sites. Process-controlled bioreactors are proposed
      as artificial ovules to impose nutritional variables from the mother tree, and to
      simulate environmental factors that are known to affect the performance of the
      new generation. Comparisons among extant and modern conifer genotypes would
      provide new insights regarding their latent potentials for apomixis, the
      alternation of generations, and adaptive plasticity.

PMID- 18822862
TI  - [Polyspermism and antipodal fertilization in Lilium (Tourn.) L. species].
AB  - It has been shown that several pollen tubes can penetrate into the embryo sac on
      the source side of the antipodal apparatus. One of the pair of sperms of
      additional pollen tube copulates with the upper antipodal, the second sperm
      copulates with the lower antipodal or rarely penetrates in the central cell. The
      process of fertilization was accomplished by the phase of nuclei morphological
      similarity characteristic ofsyngamy (by postmitotic type of fertilization
      according to Gerasimova-Navashina). A directional growth of additional pollen
      tubes involves a specifically differentiation of antipodal cells that imitates
      the egg cell.

PMID- 18822863
TI  - [Apomixis and amphimixis in flowering plants].
AB  - The light microscopic and ultrastuctural events of apomictic seed development
      from the earliest stages through the embryo and endosperm development to maturity
      were compared with those of the sexual one. The problem of autonomous endosperm
      formation was postulated as the main problem in low apomictic seed set. The
      characteristic features of fine differentiation of megasporocytes at diplospory,
      aposporous initials at apospory, embryocytes at adventive embryony as well as the
      egg cells at parthenogenesis and synergids at apogamety were described and
      compared with sexual reproductive structures. It was supposed that the observed
      similarities in differentiation at the cell level are the result of identical
      mechanisms of genetic regulation of reproductive structures at amphimixis and
      apomixis.

PMID- 18822864
TI  - Tools and methodologies for cytogenetic studies of plant chromosomes.
AB  - A brief overview is presented in advances in cytogenetic methodology and
      development of aneuploid stocks since the 1920s. The methodologies range from
      first reports of chromosome numbers of major organisms, the development of
      chromosome karyotypes, then aneuploid stocks in the major crop plants. Molecular
      inputs included chromosome banding techniques, molecular marker maps and in situ
      hybridization methodologies. All of the new techniques greatly increased the
      degree of resolution obtained from cytogenetic studies.

PMID- 18822865
TI  - [Mixoploidy in wild and cultivated Cruciferae species able to hybridize with
      Brassica napus].
AB  - Chromosome numbers in root meristem cells of the seedlings of wild and cultivated
      Cruciferae species able to hybridize with Brassica napus have been studied. The
      seedlings of Brassica junceae, Diplotaxis tenuifolia and Raphanum raphanistrum
      showed exclusively diploid metaphases. Up to 5% of B. napus and B. cretica
      seedlings were mixoploids. Diploid cells prevailed among the mixoploids, but hypo
      and hyperdiploid ones were observed as well. Nearly 20 % of B. campestris and R.
      sativum seedlings were mixoploid, and di-tetraploid chimeras constituted
      considerable proportion of them. Less than a half of B. nigra seedlings were
      diploid, while the rest of plants were mixoploid. Among them the seedlings
      bearing preferentially tetra- and triploid cells dominated. Biological
      implications and presumable reasons underlying the discovered mixoploidy are
      discussed.

PMID- 18822866
TI  - [Dependence of cross-pollination indices on genotype characteristics of winter
      common wheat].
AB  - Out-crossing indices (the out-rcrossing rate, the frequency of plants with cross
      pollination and outcrossing intensity) in F2 plants of winter common wheat from
      the reciprocal cross B-16 x Odesskaya Krasnokolosaya were analysed using storage
      proteins as genetic markers. Outcrossing indices greatly differed depending on
      growth conditions. The out-crossing rate was 0,35 % (Odessa, 2000) and 5,11%
      (Kyiv, 2004). The highest out-crossing indices were detected in homozygotes for
      the presence of the rye 1BL/1RS translocation. The out-crossing indices in
      heterozygotes for the presence of the 1BL/1RS translocation were intermediate.
      Differences in the out-crossing indices were detected between populations of F2
      plants derived from direct and reciprocal crossing. Different directions of these
      differences were noted for the out-rcrossing rate and the frequency of plants
      with cross-pollination, on the one hand, and out-crossing intensity, on the other
      hand.

PMID- 18822867
TI  - [II International Symposium "Plant growth substances: intracellular hormonal
      signaling and agricultural application". October 8-12 2007, Kiev].

PMID- 18822868
TI  - Pulmonary rehabilitation in chronic respiratory diseases--from goals to outcomes.
AB  - This paper is a review of current approaches on pulmonary rehabilitation (PR) in
      chronic pulmonary diseases. Pulmonary rehabilitation is the most accepted method
      of non-pharmacological treatment in patients with chronic obstructive pulmonary
      disease (COPD), bronchial asthma, bronchiectasis, cystic fibrosis, interstitial
      lung disease, neuromuscular degenerative disease and post-tuberculosis lung
      sequelae. Throughout its components, especially oxygen therapy, it is the most
      important intervention in chronic respiratory failure in order to improve
      exercise tolerance, lung function and self-management. Enrolling patients in
      pulmonary rehabilitation programmes is a consistent help to a better control of
      their illness and a step forward to the international standards of treating COPD
      and non-COPD chronic respiratory diseases. It is evidence-based that PR is
      effective in reducing dyspnoea, improving health-related quality of life,
      reducing the number of hospital days and the utilisation of costly healthcare
      resources; there are also psychosocial benefits from comprehensive PR programmes
      in patients with COPD. PR is currently considered as effective in patients with
      COPD and in some patients with chronic respiratory diseases other than COPD.

PMID- 18822869
TI  - [Pulmonary function tests in bronchial asthma].
AB  - Bronchial obstruction, variable over time and reversible after using
      bronchodilator is the hallmark of the respiratory function in bronchial asthma.
      There are patients with "atypical" functional tests or in whom routine tests
      (spirometry, peak-flowmetry) are not sufficient for asthma diagnosis (thus
      necessitating more complex functional tests). Pulmonary function evaluation
      confirms the diagnostic, establishes disease severity and contributes to disease
      monitoring. Quality criteria verification (e.g. acceptability of the measurements
      and reproducibility of the parameters) should precede any interpretation.

PMID- 18822870
TI  - [An improved approach in the diagnosis of mediastinal/pulmonary masses through
      the CT-guided transthoracic fine needle aspiration].
AB  - AIM: In our clinic we have gathered more than 750 cases of CT-guided
      transthoracic fine needle aspiration (FNA). This procedure is very useful for the
      diagnosis of mediastinal/pulmonary tumor masses. Because of the relatively high
      cost of this procedure, we tried to find out a less expensive but still reliable
      way to get the diagnosis for these tumors, and for this reason we figure out an
      original approach. METHODS: The study population consisted of 160 patients
      divided in two groups. To first group we applied the classic method using the
      conventional needles and the Papanicolaou stain. For the second group we used the
      spinal anesthetic needle and an original stain (blue--polychrome--tanine-
      Dragan). The chi2 test was used to match the results and complications between
      the two groups. RESULTS: This study prove that this original method is as
      reliable as the classic one but with a ten-fold reduction of costs: 1,198 euro
      versus 128 euro per 100 smears. CONCLUSIONS: Choosing of this original method for
      the diagnosis of mediastinal/pulmonary tumors through transthoracic FNA is
      justified by the low cost, simple technique and the same reliability as the
      classic method.

PMID- 18822871
TI  - [Ultrastructural aspects of intercostal muscles in patients with COPD].
AB  - The studies to the electron microscope have shown that external and internal
      intercostal muscles present characteristic changes of ultra structural
      organization in COPD. The diameter of muscle fibers become unequal, sarcolemma
      shows frequently deep invaginations, having in the near sarcoplasma
      concentrations of mitochondria and tubes of the system T. Here and there,
      myocytes appear divided or with sarcomere frequently being in contraction state.
      Ultra structural changes are more emphasized to the external intercostal muscles,
      more requested than those internal. In this way, the results show that the
      intercostal breathing muscle are affected by the chronic obstructive pulmonary
      disease.

PMID- 18822872
TI  - [Evolution of the tuberculosis epidemic in Oltenia, between 1980-2006].
AB  - The analyze of TB epidemic in Romania and, particularly, in Oltenia, in the
      condition of national applying of WHO strategy of prevention and control of TB,
      as the only way of achieving as main objective, the cure of 85% of source cases,
      represents the main way able to bring the base for adopting optimal solutions for
      correcting deficiencies. For the evaluation of the tendencies of evolution of the
      tuberculosis epidemic in Oltenia, the authors carried out a retrospective study
      over a period of more than 25 years, by the analysis of the main epidemiological
      indices of tuberculosis epidemic in this Romanian region: global incidence both
      in adults and children, for new cases and relapses apart, incidence of new cases
      of pulmonary and extra-respiratory TB, mortality through tuberculosis. In 1980,
      the TB global incidence was 71.07%000 and doubled this value in 2006. The
      distribution of new cases on regions in 2005 reflects the fact that Oltenia was
      on the first place, with a rate of 132.45%000, compared with national value of
      105.7%000 in the same year. The incidence of new cases in children in 2006
      (33.45%000) was higher than national level (31.6%000). The improvement of the
      living level of the population, following of the correct application of directly
      observed treatment and efficient anti-tuberculosis actions can determine a
      decrease of the TB epidemic in Oltenia.

PMID- 18822873
TI  - Bilateral pulmonary shadows and incapsulated mediastinal effusion in a patient
      with respiratory blastoschizomycosis.
AB  - INTRODUCTION: Invasive blastoschizomycosis is an emerging and fatal infection of
      severely immunocompromised patients. Pneumonia caused by this fungus has been
      reported as a post mortem diagnosis in a patient with haematologic malignancy.
      CASE REPORT: A 46-year-old unemployed Caucasian man, smoker, was admitted on
      emergency in a serious condition, with bilateral pulmonary infiltrates (chest x
      ray) and incapsulated mediastinal pleural effusions (computed tomography scans).
      Blastoschizomyces capitatus (Trichosporon capitatum) has been isolated from two
      sputum samples and bronchial secretion aspirate obtained by bronchoscopy.
      CONCLUSION: Pneumonia caused by Blastoschizomyces capitatus can develop in
      subjects without underlying malignancy but with history of heavy alcohol intake,
      tobacco smoking and malnutrition and may have favorable disease outcome.

PMID- 18822874
TI  - [Chronic eosinophilic pneumonia--clinical case].
AB  - Eosinophilic pneumonia (EP) is a rare, heterogeneous group of respiratory
      diseases, characterized by eosinophilic pulmonary infiltrates, with or without
      peripheral blood eosinophilia. The hallmark of chronic eosinophilic pneumonia
      (CEP) is a massive accumulation of eosinophils in the lungs, and an increased
      number of eosinophils in the bronchoalveolar lavage (BAL) fluid. We present the
      case of a 58 years-old female patient who came to the Clinical Hospital of
      Pneumology "Leon Daniello" from Cluj Napoca, Romania, with the suspicion of a
      recurrent diffuse interstitial pneumonia, despite of a proper antibiotic and
      symptomatic treatment. After clinical and paraclinical investigations the patient
      was diagnosed with idiopathic chronic eosinophilic pneumonia. Corticosteroid
      treatment was started, with rapid improvement in both clinical and radiographic
      abnormalities.

PMID- 18822875
TI  - [Respiratory symptoms of gastroesophageal reflux in children].
AB  - In the current pediatric practice, respiratory symptoms are one of the most
      common reasons that lead to referral to a pediatric specialist. Although most
      such symptoms are generated by respiratory causes, mainly infectious ones,
      sometimes extra-respiratory pathogenesis is involved. In the last twenty years,
      pediatric gastroesophageal reflux (GER) has been more frequently recognized both
      because the increased awareness of the disease and the progresses concerning the
      diagnostic techniques. The reflux-related complications and not necessarily the
      number and severity of reflux episodes are the features which help distinguishing
      between functional or physiologic and pathologic GER. The actual gold standard
      for gastro-esophageal reflux disease (GERD) diagnosis is the twenty-four-hour pH
      monitoring of the distal esophagus. Real time ultrasound examination of the eso
      gastric junction might also raise the suspicion of GERD. We report three clinical
      cases of GERD with distinct respiratory complications and non specific clinical
      picture in which anti-reflux therapy have successfully contributed symptoms
      remission.

PMID- 18822876
TI  - [Chronic cough--etiological and therapeutical considerations in the
      otorhinolaryngological practice].
AB  - Chronic cough (cough persisting more than 3 weeks) is the one of the most common
      presenting symptom in adults seeking medical care. Given the fact that the
      variety of diseases that can produce this symptom is great, the correct
      management of chronic cough should include a close cooperation between
      pneumologist, gastroenterology specialist and otorhinolaryngology specialist, in
      another words a multidisciplinary approach. The purpose of this article is to
      reveal this symptom from the otolaryngologist perspective, emphasising on the
      main diseases involved, and also on the diagnosis and treatment alternatives of
      chronic cough.

PMID- 18822877
TI  - [Bronchial thermoplasty--a new therapeutic approach in asthma].

PMID- 18822878
TI  - [Extreme solutions for those who do not succeed to quit smoking. About smokeless
      tobacco and harm reduction].
AB  - Although in the last two decades, intensified tobacco control measures have
      increased access to smoking cessation services worldwide and pharmacological
      therapy in the field had enlarged spectrum and has higher efficiency, yet, long
      term abstinence rate is no more than 20-25%. Only 70% of smokers are willing to
      quit and only 10% succeed for good. The rest of 60% plus 30% not even willing to
      quit will balance between new attempts to quit, new failures to quit and
      continuing smoking, mainly cigarettes. Among them, many heavy smokers, highly
      nicotine addicted, unable to quit, even if strongly motivated to. Harm reduction
      concept is proposing alternatives to classic cigarettes smoking, which is the
      most dangerous modality of tobacco products consumption. Such alternatives try to
      minimize as much as possible harm induced by tobacco smoking,by reducing
      carcinogenic and toxic compounds in tobacco products. Overview of smokeless
      tobacco types is given, with health risks and consumption particularities in each
      case. Scientific community in the field's opinions are presented from the
      perspective of finding ways to save as many lives as possible of smokers unable
      to quit and to change actual status quo. As part of experts predict continuous
      increasing smoking prevalence in the future unless competitive alternatives to
      cigarettes smoking are arising, such alternatives can be temporarily helpful, in
      order to assist all categories of smokers to avoid tobacco smoke (most dangerous
      form of smoking) exposure.

PMID- 18822879
TI  - [Indeterminate test results of T-SPOT.TB performed under routine field
      conditions].

PMID- 18822880
TI  - [A novel Salmonella Typhimurium plasmid, pAnkS: an example for plasmid evolution
      in antibiotic resistance].
AB  - In this study, a plasmid, carrying ampicillin resistance (ampR) gene, isolated
      from a clinical isolate of Salmonella enterica serotype Typhimurium presenting
      ACSSuT (ampicilin, chloramphenicol, streptomycin, sulphonamide, tetracycline)
      resistance phenotype, was defined. The length of complete sequence of this
      plasmid was 8271 base pairs (bp), and it was named as pAnkS owing to its
      isolation place (plasmid-Ankara- Salmonella). The plasmid was analyzed for
      potential reading frames and structural features indicative of transposons and
      transposon relics. The Xmnl enzyme restriction fragments of pAnkS were cloned
      into E. coli plasmid vectors (pBSK), sequenced and analyzed with the BLAST
      programs. Plasmid pAnkS has contained a previously defined enterohemorrhagic E.
      coli (EHEC) plasmid p4821 as a core region and also contained a complete Tn3-like
      transposon of 4950 bp consisting of the left terminal repeat, Tn3-related tnpR
      and tnpA genes for transposition functions, ampicillin resistance gene bla(TEM),
      and the right terminal repeats, pAnkS showed strong homology with another
      Salmonella plasmid, pNTP16, for sequences that belong to p4821 and partial Tn3
      segments. It was found that pNTP16 also carries kanamycin resistance gene (kanR)
      in addition to ampR gene. Plasmid pAnkS is one of the few completely sequenced
      plasmids from Salmonella Typhimurium and is in the middle of the pathway of
      evolution of plasmid from p4821 to pNTP16. The identification of pAnkS might help
      better understanding of plasmid evolution.

PMID- 18822881
TI  - [Pertussis seroprevalence and vaccination status in three selected provinces of
      Turkey].
AB  - The aim of this community-based seroepidemiological survey was to assess the
      immune status against pertussis among the healthy population in three selected
      provinces with different geographical and socioeconomical status (Antalya,
      Diyarbakir and Samsun, located at Mediterrenean, Southeast Anatolia and Black Sea
      regions of Turkey, respectively) in relation with DwPT (whole cell pertussis
      vaccine combined with diphtheria and tetanus toxoids) vaccination status. A total
      of randomly selected 2085 subjects ages between 6 months to > 50 years were
      included to the study. Serum samples have been screened for the presence of
      pertussis antibodies by an in house ELISA method with the use of pertussis toxin
      (PT) and filamentous hemagglutinin (FHA) antigens. The levels of > or = 10 EU/mL
      was accepted as positive for anti-PT and anti-FHA. Vaccination rate with 3-4
      doses among children under 15 years old was significantly lower in Diyarbakir
      compared to the other two provinces (p< 0.05). The antibody positivity was
      increased with age up to the 10-14 year group and was maintained among older
      groups. There was no statistically significant relationship between the
      vaccination rate and antibody prevalence (p> 0.05). Adult females showed a
      significantly higher antibody-positivity rate for anti-PT than the males (p<
      0.05). Our study pointed out a high prevalence of pertussis infection in those
      selected provinces, suggesting that the adults play a role as potential
      reservoirs for B. pertussis. It can be concluded that adult immunization,
      especially of those who are likely to have close contact with infants, should be
      considered.

PMID- 18822882
TI  - [Comparative evaluation of 113 cases with severe and mild forms of extrapulmonary
      tuberculosis].
AB  - Tuberculosis, one of the oldest diseases of human beings, has still high
      mortality rates. In this prospective study, 113 HIV seronegative patients with
      extrapulmonary tuberculosis (EPT) who were admitted to our department between
      January 2001 and July 2006 have been evaluated and cases with severe or mild
      forms of EPT have been compared with respect to epidemiological and clinical
      features, laboratory results and treatment outcomes. The age range of the
      patients were 16-78 years old (mean age: 46.3 +/- 16.9 years), and 64 of them
      (56.6%) were female. Severe and mild forms of EPT were diagnosed in 49 (43.3%)
      and 64 (56.6%) of the patients, respectively. The most frequently involved organ
      was detected as lymph nodes (43.3%), followed by pleura and vertebrate
      involvements with the rates of 12.4%. There was an underlying disease in 35
      (30.9%) of the patients (diabetes mellitus in 15%; chronic renal dysfunction in
      11.5%; malignancy in 4.4%), history of passed tuberculosis infection in 13
      (11.5%) and history of contact with a tuberculosis patient in 25 (22.1%). In
      direct microscopic examination, samples from 19 (16.8) patients were found
      positive for acid-fast bacilli, and samples cultivated in Lowenstein-Jensen media
      yielded mycobacterial growth in 25 (22.1%) patients. The diagnosis have been made
      histopathologically in 89 (78.7%) of the cases. In comparison of the patients
      with severe and mild forms of EPT, the severe form were detected more frequently
      in males (p= 0.01), the positivity rates of culture and acid-fast staining were
      higher in patients with severe form (p= 0.0004 and p= 0.001, respectively). The
      mortality rate was also found higher in patients with severe form (p= 0.046). The
      cases who were diagnosed as EPT have been treated by three or four
      antituberculosis drugs. Izoniazid (300 mg/day, 6-12 months), rifampicin (600
      mg/day, 6-12 months), ethambutol (1500 mg/day, 2-4 months), pyrazinamide (2000
      mg/day, 2-4 months) and streptomycin (1 g/day, 45-60 days) were used for the
      therapy. Side effects due to the therapy were observed in 13.3% of the cases
      (most frequently; gastrointestinal intolerance in 53.3% and hepatitis in 40%),
      however, there was no necessity to quit the therapy. Surgical treatment has been
      applied in 14 (12.4%) of the patients. As a result, the investigation of
      epidemiological and clinical characteristics of extrapulmonary tuberculosis on
      the large series of cases may be essential for early diagnosis and treatment in
      endemic countries such as Turkey.

PMID- 18822883
TI  - [Prevalence of inducible clindamycin resistance in Staphylococcus aureus strains
      isolated from clinical samples].
AB  - Empirical treatment options for staphylococcal infections have become limited, as
      the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) strains have
      increased. Clindamycin has been a useful option for treating skin and soft-tissue
      infections caused by MRSA. However, expression of inducible macrolide-lincosamide
      streptogramin B resistance (MLS(B)i) to clindamycin could limit the effectiveness
      of this drug. The purpose of this study was to investigate the prevalence of
      inducible clindamycin resistance (MLS(B)i) in S. aureus strains isolated from
      clinical samples (wound, abscess, blood, sterile body fluids, upper respiratory
      tract samples, catheter). We prospectively collected sequential non-duplicated S.
      aureus isolates exhibiting erythromycin resistance and clindamycin
      susceptibility, as determined by disk diffusion method from September 2005 to
      August 2007 in Baskent University Adana Research and Practice Center. Testing for
      MLS(B)i was accomplished by the disk-diffusion induction test (D test). A total
      of 892 S. aureus isolates were collected during the study period. Of these, 226
      were detected as erythromycin resistant-clindamycin susceptible by disk diffusion
      method. The prevalence of inducible clindamycin resistance in all S. aureus
      isolates and erythromycin resistant-clindamycin susceptible isolates were found
      as 19.4% (173/892) and 76.5% (173/226), respectively. Accurate susceptibility
      data are important for appropriate clindamycin therapy. Since inducible
      clindamycin resistance is not detected by standard susceptibility tests,
      application of D-test on a routine basis will be helpful to detect this
      resistance and to help effective use of clindamycin in staphylococcal infections.

PMID- 18822884
TI  - [Investigation of anti-R7V antibodies in HIV-infected patients under highly
      active antiretroviral therapy].
AB  - R7V is a seven-aminoacid peptide epitope derived from cellular beta-2
      microglobulin, present on human immunodeficiency virus (HIV) virion surface in
      patients with HIV infection. Antibodies against R7V peptide have the property of
      neutralizing all strains of HIV, unrelated to genotype, phenotype, or
      geographical origin of the virus, even in the presence of anti-retroviral drug
      resistance. Patients that mount an anti-R7V antibody response have been shown to
      be slow or non-progressors and this epitope has been considered for vaccine
      and/or therapeutic uses. In this study, HIV-infected patients under highly active
      anti-retroviral therapy (HAART) at Hacettepe University Faculty of Medicine,
      Department of Internal Medicine, Division of Infectious Diseases, were evaluated
      for the presence of anti-R7V antibodies. Thirty-three HIV positive patients and
      10 healthy controls were enrolled to the study. For HIV-infected patients,
      determination of viral load and CD4+ T lymphocyte counts were performed by a
      commercial real-time PCR assay and flow cytometry, respectively. Anti-R7V
      antibodies were detected from serum samples by a commercial ELISA (Anti-R7V
      ELISA, Ivagen, France) test. Three HIV infected patients (3/33, 9.1%) displayed
      anti-R7V antibodies whereas the remaining 30 (90.9%) patients and all controls
      were interpreted as negative. No statistically significant difference was
      detected for HIV-RNA levels and CD4+ T lymphocyte counts between anti-R7V
      positive and negative patients (p= 0.871 and p= 0.287, respectively). These
      results indicate the presence of anti-R7V antibodies in our study population with
      HIV infection. No correlation with the presence of anti-R7V and disease
      progression were displayed in this study. Clinical impact of anti-R7V antibody
      assays for the management of HIV-infected patients will be revealed in the near
      future with the help of advanced studies.

PMID- 18822885
TI  - [Investigation of herpes simplex virus in viral meningoencephalitis suspected
      cases using molecular and serological methods].
AB  - Herpes simplex virus (HSV) meningoencephalitis has a high mortality rate if
      proper antiviral therapy is not applied. Thus rapid diagnosis is of peculiar
      importance in such cases. In this study we aimed to evaluate the use of
      polymerase chain reaction (PCR) and detection of intrathecally synthesized
      antibodies by serological methods in viral meningoencephalitis suspected cases to
      determine HSV as the causative agent. Seventeen cases with cerebrospinal fluid
      (CSF) samples with microscopical and biochemical findings compatible with viral
      encephalitis were included in this study. CSF samples yielded no bacterial
      growth. Cell cultures propagated in Vero cell line and PCR with different primer
      sets against HSV-1 and HSV-2 (specific for US7 and US2 gene regions,
      respectively) were used to investigate the presence of HSV in CSF. Serum samples
      were taken simultaneously with the CSF sampling and "Reibergram" graphics and
      antibody index (AI) calculations were used for the evaluation of intrathecal
      antibody synthesis. Albumin and total IgG levels in serum and CSF samples
      measured with nephelometry (Dade-Behring, Germany) for Reibergram graphics,
      albumin and IgG ratios were calculated. Quantitative levels of HSV 1+2 IgG were
      measured in serum and CSF samples using ELISA (HSV-1/2 Pool; Antibody
      Determination in CSF, Euroimmun, Germany) for AI determination. One of the CSF
      samples obtained one week after the neurological symptoms had started, yielded
      HSV-2 in cell culture and also HSV-2 DNA was detected by PCR. Intrathecal
      antibody synthesis was not detected in this case. In two cases with symptoms
      lasting for more than three weeks, intrathecal IgG synthesis in Reibergrams and
      pathological intrathecal HSV AI (27.9 and 7.9, respectively) were detected,
      however, virus isolation and PCR detection were not successful. For the other 14
      cases, HSV-DNA were found negative and no intrathecal antibody synthesis were
      detected. HSV meningoencephalitis can be diagnosed via using PCR which has been
      accepted as gold standard in recent years, with 24 hours turn-around time.
      However, if CSF samples were taken later than the first week following the
      beginning of symptoms, possibility of HSV detection by PCR is lowered. According
      to the data obtained from this limited study, it may be suggested that PCR may be
      used for the detection of HSV-DNA in CSF samples during the early phase of
      meningoencephalitis cases, however, consideration must be taken to detect the
      intrathecal antibodies during the later phases of the infection where intrathecal
      antibody synthesis starts.

PMID- 18822886
TI  - [Common viral etiologies of community acquired lower respiratory tract infections
      in young children and their relationship with long term complications].
AB  - Viral lower respiratory tract infections (LRTIs) and their late complications are
      important causes of morbidity and mortality in childhood. The aims of this study
      were the detection of viral agents that cause community-acquired LRTIs in young
      children and investigation of the relationship between viral etiology and
      bronchiolitis obliterans (BO) which is one of the late complications of LRTIs. A
      total of 151 children (86 male, 65 female; mean age: 2.9 +/- 1.9 years) who were
      diagnosed to have LRTIs between the period of 2002-2004, at Pediatric Allergy and
      Pulmonology Department of a University Hospital in Manisa (located in the Aegean
      region of Turkey) were included to the study. The presence of respiratory viruses
      [respiratory syncytial virus (RSV), influenza virus type A and B, parainfluenza
      virus types 1, 2 and 3, adenovirus] in the nasopharyngeal aspirate specimens
      collected from children have been searched by direct fluorescence antibody test
      (Biotrin, Ireland). Respiratory viruses were detected in 25.2% (38/151) of the
      patients with LRTIs, while this rate was 46.8% (22/47) for 2002 period, 13.3%
      (8/60) for 2003 period and 18.2% (8/44) for 2004 period. RSV and adenoviruses
      both detected with a frequency of 31.5% (n= 12/38); were the most common agents
      encountered, and followed by parainfluenza (10/38, 26.3%) and influenza (9/38,
      23.6%) viruses. Postinfectious BO have been diagnosed in 7.3% (11/151) of the
      patients; seven in 2002, one in 2003 and three in 2004 periods. Viral etiology
      were present in all of the patients who developed BO in 2002, while viral
      infection was detected in one of the patients who developed BO in 2003-2004
      periods. Adenoviruses were the most frequently detected agents (n= 5) in BO cases
      with viral etology (n= 8). Viral agents were found positive in 72.7% (8/11) and
      21.4% (30/140) of the patients with and without BO development, respectively, and
      this difference was found statistically significant (p= 0.02). Besides, BO
      development was detected in 21.1% (8/38) and 2.6% (3/113) of LRTI patients with
      and without viral etiology, respectively, and this difference was also
      significant (p< 0.05). In conclusion, the long term follow-up is important in
      young children with viral LRTIs for the early diagnosis of complications. Thus
      the identification of viruses might aid in estimation of prognosis.

PMID- 18822887
TI  - [Investigation of viral nucleic acids in middle-ear effusion specimens from
      children with acute otitis media].
AB  - Acute otitis media with effusion (OME) is one of the major causes of antibiotic
      use, indication for operation and hearing loss in children. In two third of the
      cases the etiologic agents are bacteria. Nonetheless, increasing numbers of
      reports have implicated viruses as etiologic agents that may have some effect on
      prognosis of OME. The aim of this study was to investigate the presence of
      nucleic acids of respiratory syncytial virus (RSV) type A and B, influenza type A
      virus, adenovirus, cytomegalovirus (CMV), herpes simplex virus type-1 (HSV-1),
      and enteroviruses in the middle ear effusion specimens from children with otitis
      media by TaqMan real-time PCR. As a result, 18 of 30 (60%) OME samples were found
      positive in terms of viral nucleic acids by real-time PCR. RSV-A was detected in
      nine samples (30%), CMV in 3 (10%) samples and HSV-1 in 1 (3.3%) sample. In five
      of the samples two viruses were detected in the same sample (three were positive
      for adenovirus and RSV-A, and two were positive for CMV and RSV-A). Our data have
      supported the importance of viruses as etiologic agents of OME. Additionally, it
      was thought that TaqMan real-time PCR may be used as a reliable and rapid method
      for the detection of viruses in the middle ear effusion samples.

PMID- 18822888
TI  - [YMDD motif variants detected by Inno-Lipa HBV DR assay in chronic hepatitis B
      patients during lamivudine therapy].
AB  - Lamivudine resistance is a result of mutations in YMDD motif in which rt203-206th
      codons (Y: tyrosine; M: methionin; D: aspartic acid; D: aspartic acid) of reverse
      trancriptase; the catalytic part of hepatitis B polymerase enzyme, takes place.
      In this study we aimed to show the YMDD motif variants in chronic hepatitis B
      patients who have presumably developed lamivudine resistance due to viral
      polymerase gene mutation during lamivudine therapy. Twenty lamivudine treated
      patients were included in the study, and HBV-DNA was extracted from the sera of
      the patients by using extraction kit (Invisorb, Instant Spin DNA/RNA Virus Mini
      Kit, Germany). A line probe assay (INNO-LIPA HBV DR; INNOGENETICS N.V, Ghent,
      Belgium) was used to determine YMDD motif variants at viral polymerase gene
      fragment in HBV-DNA samples of these patients and evaluated colorimetrically. In
      12 (60%) patients' samples YMDD motif variants were detected leading to lamivudin
      resistance. Eleven (91.6%) of the 12 samples having motif variants were YMDD
      variant and wild-type combination. While YMDD + YIDD combination was determined
      in only one specimen, YMDD + YVDD combination was determined in six. Mixed
      combination of YMDD + YVDD + YIDD were detected in four samples. In 8 (66.6%) HBV
      DNA samples YMDD variants were accompanied with L180M variants. It can be
      concluded that determination of genotypic resistance before the expression of
      phenotypic resistance during lamivudin therapy is important since addition of
      adefovir to the therapy at an early stage will prevent the occurence of hepatitis
      with mutant species. Thus lamivudin resistance should be followed up regularly in
      all of the chronic hepatitis B patients under lamivudin therapy.

PMID- 18822889
TI  - [Epidemiological features of Candida infections detected in intensive care units
      and risk factors affecting mortality].
AB  - The aim of this study was to describe the epidemiological features of nosocomial
      Candida infections in intensive care units and to detect the risk factors which
      increase the mortality rate. A total of 940 patients hospitalized in ICUs of
      Gulhane Military Medical Academy Haydarpasa Training Hospital, Istanbul, between
      January 01 and December 31, 2006 were prospectively enrolled into this study.
      Candida spp. were isolated from various clinical specimens (blood, urine,
      respiratory tract, wound) in 48 patients. Of these patients, 50% were male and
      50% were female, and the mean age was 63.66 +/- 22.72 (age range: 8-92) years.
      The mean duration of hospital stay was 36.25 +/- 44.51 (min: 1, max: 90) days.
      Thirty five Candida infection attacks were observed in 29 of 48 patients. C.
      albicans was isolated in 18 infections and non-albicans Candida spp. in 17
      infections. Nosocomial infection rate due to Candida spp. was 3.22 per 1000
      patient-days. The most common Candida infections were bloodstream (42.9%) and
      urinary tract infections (37.1%). At the time of diagnosis, 89.6% of patients
      were being hospitalized for more than ten days and 69% of the patients were using
      three or more wide spectrum antibiotics. Diabetes mellitus and cardiovascular
      diseases were the most frequently detected co-morbid diseases. The overall
      mortality rate was 55.2%. Predictors of adverse outcome were diabetes mellitus
      (p= 0.016), need for mechanical ventilation (p= 0.010) and infection with non
      albicans Candida spp. (p= 0.002). In conclusion, Candida infections in the
      intensive care patients are associated with high mortality. Mortality due to
      Candida infections could be reduced by defining the risk factors and starting
      preemptive antifungal treatment to patients who are under risk.

PMID- 18822890
TI  - [Investigation of keratinophilic fungi in Laodicea's recreation workshop].
AB  - Recreation ateliers in which archeological remnants are operated to be restorated
      to their original forms, are closed places with high humidity rates. The hands
      and the nails of archeology workers contact directly with the keratinophilic
      fungi during recreation facilities. The aim of this study was to investigate the
      presence and distribution of keratinophilic fungi in Laodikeia antique city's
      recreation atelier (Pamukkale region; Aegean part of Turkey). A total of 18
      archeological remnant samples were collected from Laodikeia recreation atelier
      during the digging period of 2006. The samples were screened for the prevalence
      of keratinophilic fungi by hair baiting technique and the isolates were
      identified by conventional mycological methods. Of the samples 38.9% (7/18) were
      found positive and the distribution of keratinophilic fungi were as follows;
      Chrysosporium spp. (22.2%) (two of them were C. keratinophilum), Aphanoascus spp.
      (11.1%), Auxarthron spp. (5.5%) and Trichophyton rubrum (5.5%). It was concluded
      that the patient histories including living and working conditions, may be
      helpful to identify the keratinophilic fungi growing on cycloheximide containing
      mycologic media and archeology workers should be informed for the diseases caused
      by environmental keratinophilic fungi.

PMID- 18822891
TI  - [Biosafety profile of laboratory workers at three education hospitals in Izmir,
      Turkey].
AB  - The laboratory personnel in hospitals are at risk in terms of transmission of
      various infectious diseases. The aim of this study is to evaluate the knowledge,
      behavior and attitude of the health personnel who work in one university and two
      state hospitals in Izmir, Turkey, about biosafety. The study is an observational
      sectional study. Participants were selected via random sampling method. The
      hospitals were visited on workdays determined by the random selection method and
      all of the personnel (doctor, technician, cleaning-staff) were included to the
      study. The data were analyzed statistically using Chi square test. Of the 183
      participants included in the study, 106 were from Dokuz Eylul University School
      of Medicine Central Laboratory and 77 were from state hospitals. 62.8% of the
      participants were female, 37.2% were male and mean age of all was 32.8 +/- 6.9
      years. 23.5% of the participants stated that they had previously taken education
      about biosafety (p= 0.002). It was determined that 91.3% of the participants were
      wearing gloves and 87.4% of them were wearing lab-coat during laboratory studies.
      A significant difference was observed between the hospitals in terms of use of
      gloves (p= 0.004). All the participants stated that they wash their hands and 43%
      of them indicated that their daily hand wash rate was > or = 10 times. It was
      determined that 38.3% of the participants consumed food or drinks in the
      laboratory, however, this rate was statistically significantly less in the
      university hospital laboratory (p= 0.000). The rate of participants who had been
      subjected to a microorganism in the last six months was 6.6%. Obedience to the
      biosafety rules in laboratory will not only provide a safer environment but also
      improve the quality of work. We believe that the results of this study will serve
      as a guide for future studies on laboratory biosafety.

PMID- 18822892
TI  - [Susceptibility testing of Mycobacterium tuberculosis isolates to primary
      antituberculous drugs on chocolate agar: a preliminary study].
AB  - The aim of this study was to evaluate the use of chocolate agar as an alternative
      medium instead of Middlebrook 7H10 agar, for the susceptibility testing of
      Mycobacterium tuberculosis strains against isoniazid (INH), rifampicin (RIF),
      streptomycin (STR) and ethambutol (ETM). The susceptibility results obtained by
      chocolate agar were compared with the results of BACTEC 460 TB (Becton Dickinson,
      Sparks, MD, USA) system which was accepted as the reference method. A total of 25
      M. tuberculosis clinical isolates were included to the study and susceptibility
      testing was performed on malachite green added-chocolate agar with some
      modifications of proportion method recommended by NCCLS. In our study when
      comparing the results obtained by chocolate agar with the results of BACTEC 460
      TB system, the concordance rates for INH, STR, RIF and ETM were found as 88%,
      88%, 84% and 72%, respectively. The specificity, sensitivity, positive and
      negative predictive values of susceptibility testing on chocolate agar have been
      detected as 82.3%, 100%, 72.7% and 100% for INH; 78.5%, 100%, 78.5% and 100% for
      RIF; 83.3%, 84.2%, 94.1% and 62.5% for STR; 25%, 94.1%, 72.7% and 66.6% for ETM,
      respectively. The results of the susceptibility testing performed on chocolate
      agar were obtained on the 21st day of incubation for all isolates. In conclusion,
      the data from our study suggested that chocolate agar can be used as an
      alternative medium for the susceptibility testing of M. tuberculosis, however,
      further studies with more isolates are needed for the standardisation of the
      method.

PMID- 18822893
TI  - [Investigation of anticardiolipin antibodies in chronic hepatitis B infection
      together with total anti-delta positivity].
AB  - Anticardiolipin antibodies (ACAs) are formed against phospholipids in various
      clinical conditions such as autoimmune diseases, malignancy, infectious diseases,
      alcohol-related and hepatic cirrhosis. The aims of this study were to investigate
      the presence of ACAs in patients with chronic hepatitis B together with positive
      total anti-delta antibodies, and to investigate the relationship between age,
      gender, and some laboratory parameters (ALT, AST, albumin, globulin, platelet
      number) of patients with chronic hepatitis delta virus (HDV) infection, who were
      positive or negative for ACAs. A total of 60 patients (43 male, 17 female) with
      chronic hepatitis D infection [HBsAg positive, HBeAg negative, anti-HBe positive,
      anti-HBc IgG positive, anti-HBc IgM negative, total anti-delta positive, anti-HCV
      negative] and 30 patients (21 male, 9 female) without hepatitis D infection
      [HBsAg positive, HBeAg negative, anti-HBe positive, anti-HBc IgG positive, anti
      HBc IgM negative, total anti-delta negative, anti-HCV negative] as control group
      were included to the study. ACA IgG and IgM were searched by a commercial
      microELISA kit (Euroimmun, Germany). The statistical evaluation was performed
      with Pearson's chi-square test, Student's t-test, and Fisher's exact test. Total
      ACAs positivity rate of 60 patients with chronic HDV infection, was found as
      13.3%, in which four of the patients were positive for only ACA IgM, while four
      was positive for only IgG. Positivity for both ACA IgG and ACA IgM could not be
      detected in these patients. No patients in the control group had positivity for
      ACAs (IgG and/or IgM). A statistically significant difference was observed in
      terms of ACA positivity between patients with and without HDV infection (p<
      0.05). After all, there was no statistically significant correlation between ACAs
      positivity and the age, sex, and laboratory parameters of the patients with
      chronic HDV infection, except lower serum albumin levels (p= 0.004). Although the
      data of this study revealed a statistically significant positive correlation
      between chronic HDV infection and anticardiolipin antibodies, it is clear that
      there is a need for further studies on this subject.

PMID- 18822894
TI  - [Pulmonary nocardiosis with a large solitary cavitary nodule caused by Nocardia
      cyriacigeorgica in a patient receiving corticosteroid therapy].
AB  - Nocardiosis is a rare disease generally caused by members of Nocardia asteroides
      complex, particularly in immunosupressed patients. Nocardia cyriacigeorgica is a
      newly described member of this complex. In this article, a case of pulmonary
      nocardiosis with a large solitary cavitary nodule caused by N. cyriacigeorgica,
      in a patient receiving corticosteroid therapy was presented. A 29 years old male
      patient receiving prednisolone for 5 months was admitted to our hospital with
      fever, cough, right thoracic pain and night sweats. Computed tomography scan of
      chest demonstrated a large solitary cavitary nodule in the right lower lobe. Gram
      stained smear of the sputum revealed gram-positive, beaded, branched filamentous
      bacilli. On the third day of his admission, a catalase positive, oxidase negative
      and immotile bacilli, compatible with Nocardia spp., were isolated from the
      sputum sample taken at the day of admission. The isolated bacterium was
      identified as N. cyriacigeorgica by reference laboratory (Lyon, France). Oral
      trimethoprim (320 mg/day) and sulfamethoxazole (1600 mg/day) therapy given for
      three months, resulted in complete cure of the lesion without any sequela. This
      was the fourth case of pulmonary nocardiosis caused by N. cyriacigeorgica
      reported from Turkey. Microbiological examination of sputum is the most important
      tool for the diagnosis. Treatment with appropriate antibiotics may achieve
      complete cure even in large cavitary lesions. In conclusion, pulmonary
      nocardiosis should be considered in differential diagnosis of solitary cavitary
      nodules, especially in immunocompromised patients.

PMID- 18822895
TI  - [Nosocomial meningitis with dual agents and treatment with intraventricular
      gentamicin].
AB  - Nosocomial central nervous system infections constitute 0.4% of all nosocomial
      infections. The responsible pathogens of nosocomial meningitis are quite
      different from community-acquired meningitis with high rates of morbidity and
      mortality. The most important prognostic factor is the appropriate choice of
      pathogen-specific antibacterial therapy. In this report, a 64 years old woman
      with nosocomial meningitis caused by Klebsiella pneumoniae and Acinetobacter spp.
      after lumbar disc hernia operation, has been presented. The risk factors were
      detected as recent history of neurosurgical operation for three times and long
      term (29 days) use of external ventricular drainaige (EVD) catheter. Empirical
      meropenem (3 x 2 g, IV) and vancomycin (2 x 1 g, IV) therapy was initiated upon
      the diagnosis of nosocomial meningitis based on the clinical and laboratory
      findings on the postoperative fifth day. Extended-spectrum beta-lactamase (ESBL)
      producing K. pneumoniae (susceptible to amikacin, imipenem, meropenem,
      cefoxitine, ciprofloxacin, piperasillin-tazobactam and
      trimethoprim/sulfamethoxazole) was recovered from cerebrospinal fluid (CSF) and
      blood samples obtained on the same day. There was no change in the status of the
      patient on the eighth day of meropenem therapy, with high leukocyte number
      (1300/mm3) and presence of gram-negative bacilli in CSF, and ESBL positive K.
      pneumoniae (antibiotic susceptibility pattern same with the previous isolate)
      growth in CSF culture. Thereupon intravenous ciprofloxacin (3 x 400 mg) was added
      to the therapy and her EVD has been changed. However, ESBL positive K. pneumoniae
      (antibiotic susceptibility pattern same with the previous isolate) together with
      Acinetobacter spp. (susceptible to gentamycin, tobramycin, netilmicin,
      ciprofloxacin, levofloxacin and cefepime) were isolated from CSF and blood
      cultures obtained on the 13th day of meropenem and fifth day of ciprofloxacin
      therapy. Therefore intraventricular and intravenous gentamicin (15 mg/days and 3
      x 120 mg, respectively) were added to the therapy. The patient recovered at the
      end of three weeks treatment without any additional sequela other than her
      primary illness. This case was the first case of nosocomial meningitis due to
      ESBL positive K. pneumoniae together with Acinetobacter spp. in the available
      literature.

PMID- 18822896
TI  - [Sternal tuberculosis].
AB  - Isolated involvement of the sternum is rare, representing less than 1% of
      tuberculous osteomyelitis. In this report, a 51-years-old woman who was admitted
      to the hospital with a localized solid mass in the sternum has been presented. A
      soft, painful mass measuring 3 cm in diameter in the lower sternum was detected
      during physical examination. Radiological investigation revealed presternal soft
      tissue and bone expansion in the posterior side of lower sternum. The patient was
      treated with non-specific antibiotics for a suspected diagnosis of osteomyelitis
      but the lesion did not show any regression. Since the microbiological analysis of
      fine needle aspiration fluid demonstrated acid-fast bacilli in direct microscopy
      and Mycobacterium tuberculosis was isolated from the culture, anti-tuberculous
      therapy consisting of isoniazid (INH), rifampicin (RIF), pyrazinamide (PZA), and
      ethambutol (ETM) was started. Sputum and urine cultures of the patient yielded
      negative results in terms of tuberculosis. After the first month of the therapy,
      her skin lesion was completely healed. Since the strain was found to be resistant
      to isoniazid, the maintenance therapy has been applied as INH + RIF + PZA for
      nine months. The history of the patient indicated that one of her relatives had
      skin tuberculosis on the face. As a result the patient has been successfully
      treated with anti-tuberculosis combination therapy together with surgical
      debridement.

PMID- 18822897
TI  - [Infective endocarditis due to high level aminoglycoside resistant Enterococcus
      faecalis and methicillin resistant coagulase-negative staphylococci presenting
      with rheumatic manifestations].
AB  - Infective endocarditis has variable clinical presentations and may present with
      rheumatologic manifestations. Infective endocarditis due to high level
      aminoglycoside resistant enterococci represents a severe therapeutic challenge as
      none of the currently recommended treatment regimens are bactericidal against
      these isolates. In this report, a case of infective endocarditis with double
      aetiology, high level aminoglycoside resistant Enterococcus faecalis together
      with methicillin-resistant coagulase-negative staphylococci (MR-CNS), presenting
      with leukocytoclastic vasculitis and rapidly progressive glomerulonephritis, has
      been presented. A 48-years-old woman was admitted to our hospital with malaise
      and non-pruritic purpural rush on her lower extremities. On admission she had no
      fever or leukocytosis. Skin biopsy showed leukocytoclastic vasculitis and steroid
      therapy was started. On 12th day of admission rapidly progressive
      glomerulonephritis was diagnosed and she received plasmapheresis and
      haemodialysis support. Transthoracic echocardiography (TTE) demonstrated 1 x 1.5
      cm vegetation on the mitral valve. An initial diagnosis of infective endocarditis
      was made and empirical treatment with vancomycin and gentamicin was started. All
      blood cultures yielded high level aminoglycoside resistant E. faecalis and
      additionally two of them yielded MR-CNS. Vancomycin was administered in
      combination with high dose ampicillin and repeated blood cultures taken after
      administration of ampicillin, revealed no growth. The patient remained afebrile,
      renal functions improved and a repeat TTE done on 20th day of ampicillin therapy
      showed waning of the vegetation. On 42nd day of treatment repeat TTE showed new
      vegetation on the mitral valve and severe valve insufficiency, so the patient was
      scheduled for mitral valve replacement. She was treated for 12 weeks with
      vancomycin and ampicillin and recovered successfully. In conclusion; infective
      endocarditis should be considered in the differential diagnosis of
      leukocytoclastic vasculitis and rapidly progressive glomerulonephritis.
      Physicians should document their treatment outcomes and experience with high
      level aminoglycoside resistant enterococcal infective endocarditis, which is a
      therapeutic challenge, so that the best therapeutic options can be identified.

PMID- 18822898
TI  - [Streptococcus equisimilis associated septic arthritis/prosthetic joint
      infection].
AB  - Group C streptococci are flora members of skin, nasopharynx, gastrointestinal and
      genitourinary systems. They are rare causes of human pharyngitis, arthritis,
      pneumonia, meningitis and bacteremia. In this report, a 71-years old male patient
      with Streptococcus equisimilis arthritis/prosthetic joint infection has been
      presented. The patient was admitted to the emergency service with the complaints
      of erythema, swelling and tenderness on right knee which had total knee
      prosthesis. Examination of synovial fluid punction sample yielded abundant amount
      of leukocytes (> 1000 cells/mm3). Empirical ampicillin-sulbactam (1 g q6h,
      parenterally) therapy was initiated. Bacteria which have been cultivated from
      synovial fluid specimen were identified as S. equisimilis. The isolate was found
      to be susceptible to penicilin, erythromycin and teicoplanin, and resistant to
      chloramphenicol and tetracycline. Although clinical presentation improved during
      the first ten days, symptoms recurred after the 10th day and the therapy was
      switched to teicoplanin. The recurrence was thought to be the result of
      antibiotic tolerence. The patient was treated successfully with teicoplanin, and
      no relapse or reinfection was observed during one year of follow-up. To our
      knowledge this is the first case of S. equisimilis arthritis reported from Turkey
      and first case of S. equisimilis associated prosthetic joint infection.

PMID- 18822899
TI  - [Cryptococcus neoformans meningitis in a HIV negative miliary tuberculosis
      suspected patient].
AB  - Cryptococcosis caused by Cryptococcus neoformans has a wide range of clinical
      presentations, varying from asymptomatic colonization of the respiratory airways
      to the dissemination of infection into different parts of body. It is more common
      among immunosupressed patients such as human immunodeficiency virus (HIV)
      positive ones. In this report we present a case with C. neoformans meningitis and
      miliary pulmonary infiltrates suggesting pulmonary tuberculosis without HIV
      infection. A-70-years-old male was admitted to the hospital with mental
      confusion, 3-weeks history of headache, weight loss, dry cough and fatigue.
      Physical examination was normal except neck stiffness. Cerebrospinal fluid (CSF)
      white cell count was 120/mm3 (80% polimorphonuclear cells). Gram staining of CSF
      revealed poorly stained gram-positive yeast cells. Empirical therapy with
      lipozomal amphotericin B, ceftriaxone and ampicillin combination was started.
      When C. neoformans growth was detected on CSF culture, ceftriaxone and ampicillin
      were discontinued. Patient became conscious at 24th hour of the treatment.
      Peripheric blood flow-cytometric analysis revealed a significant decrease in
      absolute CD4+ T lymphocytes, and in CD8+28+ T lymphocytes in addition a
      significant increase in natural killer cell ratio. Blood immunoglobulin and
      complement levels were found normal. Cranial magnetic resonance imaging and
      computerized tomogralphy (CT) of the abdomen were normal, however, chest CT
      revealed multiple parenchymal millimetric nodular infiltrations on both sides and
      minimal fibrotic alterations. Acid-fast staining of CSF, tuberculosis culture,
      tuberculosis PCR results and repeated HIV serology were found negative. Despite
      the lack of microbiological confirmation, empirical antituberculosis treatment
      was also started with the suspicion of miliary tuberculosis as the patient had a
      symptom of long-term dry cough, miliary infiltrations on chest CT, anergic
      tuberculin skin test and a history of pulmonary tuberculosis in childhood. After
      two weeks, amphotericin B was changed to oral fluconazole which was continued for
      an additional eight weeks. Antituberculosis therapy was given for nine months.
      Control chest CT taken after four months of antituberculosis therapy revealed
      improvement of the lesions. This presentation emphasizes the fact that
      cryptococcal infections may develop in HIV negative patients, even together with
      tuberculosis in certain cases and radiological findings of the two infections may
      be confusing when both of them invade the lungs.

PMID- 18822900
TI  - [Treatment of chronic hepatitis C virus infection in hemodialysis patients].
AB  - Hepatitis C virus (HCV) is the most common pathogen leading to serious morbidity
      and mortality in hemodialysis patients. The prevalence of HCV infection detected
      in dialysis patients in developing countries such as Turkey is generally much
      higher than those in developed countries. The prevalence of HCV infection among
      hemodialysis patients has been reported between 31.4% to 51% in Turkey.
      Interferon based therapy is the mainstay of treatment for HCV related liver
      disease in dialysis patients however, it is not recommended after renal
      transplantation because of the risk of acute rejection and graft dysfunction.
      Therefore it is important to eradicate HCV-RNA before transplantation. Currently
      available pegylated interferons have much higher efficacy against HCV than
      conventional interferons in the dialysis patients. Pegylation delays clearence of
      interferon and it leads to a more potent and longer antiviral effect. Two
      pegylated interferon (Peg-IFN) formulations with different pharmacokinetic
      characteristics are currently available (Peg-IFN alpha-2a and Peg-IFN alpha-2b).
      In view of the high prevalence of adverse effects associated with Peg-IFN, an
      increased awareness of their use in dialysis patient population is reasonable.
      However, there are few published studies on interferon therapy in hemodialysis
      patients. These studies confirm that the response rate to different interferon
      formulations is much higher than the general population but with a higher rate of
      adverse events. Ribavirin is usually not recommended in patients with chronic
      renal failure since the drug is not removed during conventional dialysis and its
      accumulation causes a dose dependent hemolytic anemia. Use of ribavirin plus
      interferons should still be limited to controlled clinical studies. Results
      obtained in recent clinical trials should be confirmed by large prospective,
      randomized, multi-center studies. In this review article the treatment of
      hemodialysis patients with chronic hepatitis C has been discussed under the light
      of recent literature.

PMID- 18822901
TI  - [High rate of hepatitis B virus DNA positivity in anti-HBc only-positive
      patients].
AB  - In hepatitis B virus (HBV) infections, detection of only anti-HBc in the absence
      of HBsAg and anti-HBs is known as 'anti-HBc only' situation. In this study we
      investigated the rate of HBV-DNA positivity in anti-HBc only-positive 45 patients
      (29 male, 16 female; mean age: 39.2 +/- 12.3 years) who were followed in the
      outpatient clinics of a University Hospital in Duzce (located at northern west
      part of Turkey). HBV markers were investigated by 3rd generation ELISA (MEIA
      Axsym-Abbott), and HBV-DNA were searched by real-time PCR [extraction: Minielute
      (Qiagen, Germany); PCR kits: Florion HBV (lontek, Turkey); detection: i-cycler
      IQ5 (BioRad, USA)] methods. As a result, 24.4% (11/45) of the patients were found
      HBV-DNA positive (> 10(3) copies/ml). There was no statistically significant
      difference of HBV-DNA positivity rates between males (9/29; 31%) and females
      (2/16; 12.5%), (p= 0.15). It was concluded that there may be a serious risk of
      HBV transmission from anti-HBc only-positive patients since the rate of HBV-DNA
      positivity was found high in our study. Thus HBV-DNA screening should be
      performed in 'anti-HBc only' patient groups.

PMID- 18822902
TI  - [Structure and prospect of osteoimmunology of integrative medicine].

PMID- 18822903
TI  - [Regulatory effect of bushen jianpi recipe on cellular immunity of patients with
      primary liver cancer after intervention therapy].
AB  - OBJECTIVE: To observe the regulatory effect of Bushen Jianpi Recipe (BSJPR) on
      cellular immunity the of primary liver cancer patients of Gan-Shen yin-deficiency
      and Pi qi-deficiency syndrome type after intervention therapy. METHODS: According
      to the multi-center randomized controlled principle, 117 patients after
      transcatheter arterial chemoembolization (TACE) were assigned to two groups, 60
      in the treated group and 57 in the control group, who were treated respectively
      with BSJPR and liver protecting remedy (silymarin and vitamin c) for 12 weeks.
      Changes in TCM syndrome, quality of life (QOL), immediate effect on tumor size
      and survival time were observed. Meantime, the cellular immune function was also
      observed, including the T lymphocyte response determined by 3H-TdR, expression of
      MHC class I/II and B7 molecule detected by FACS, and interleukin 10 and 12 (IL
      10, IL-12), interferon-gamma (IFN-gamma) tested by ELISA. RESULTS: In the treated
      group after treatment, the efficacy for improving TCM syndrome reached 73.33%
      (44/60 cases), their half-year survival rate being 83.33% (50/60 cases); while
      those in the control group were 52.63% (30/57 cases) and 70.18% (40/57 cases)
      respectively, significant difference was shown between the two groups (P <0.05).
      The patients' QOL was improved in the treated group after treatment, with no
      obvious adverse reaction. However, the clinical benefit rate in the control group
      (92.7%, 51/55 cases) was higher than that in the treated group (78.0%, 46/59
      cases, P =0. 035). Laboratory examination showed increases of MHC class II
      (CD14+/HLA-DR) expression on monocyte surface as well as IFN-gamma and IL-12
      production in the treated group. CONCLUSION: Using BSJPR together with TACE could
      enhance patients' cellular immune function to elevate the clinical curative
      effect on primary liver cancer.

PMID- 18822904
TI  - [Quality assessment of the report of randomized controlled trials on treatment of
      liver carcinoma with traditional Chinese medicine].
AB  - OBJECTIVE: To investigate the published randomized controlled trials (RCTs)
      concerning the treatment of liver carcinoma with TCM, and to assess their
      methodologic quality and quality of report. METHODS: Related RCT reports
      published from Jan. 2004 to June 2006 were retrieved by computerized and manual
      search, and the criteria of CONSORT statement (revised edition) were applied to
      assess the articles searched. RESULTS: Forty-six articles up to the RCTs
      inclusion standard were searched, among them, the method for randomized
      distribution sequence producing was described in 9 articles (19.57%), none
      mentioned randomization concealment and the estimation of the sample size. The
      blinded method was adopted in 3 articles (6.52%), the inclusion and exclusion
      criteria were reported in 18 (39.13%) and 1 (2.17%), respectively. Participant
      flow was reported in 3 (6.52%), but flow chart was not described in any article.
      Patients' compliance was reported in 5 (10.87%), and the concrete P value was
      reported in 6 (13.04%), but with no report involving the confidence interval.
      Adverse events were described in 15 (32.61%). Only 5 articles (10.87%) discussed
      the limitations of the present study in their section of discussion. CONCLUSION:
      The quality of RCTs reports on treatment of liver carcinoma with TCM are still in
      low quality, not meeting the CONSORT statement.

PMID- 18822905
TI  - [Effect of Chinese herbal medicine in the natural cycle of frozen embryo
      transfer].
AB  - OBJECTIVE: To study the effect of Chinese herbal medicine on the clinical
      pregnancy rate and implantation rate of frozen embryo transfer (FET) in a natural
      cycle. METHODS: Women with frozen embryos planned to receive FET and had
      spontaneous ovulation in a natural cycle were chosen for observation. They were
      assigned to the treated group and the control group, both were treated with
      conventional medicine in the very month of FET, but to the treated group, Chinese
      herbal medicine was given additionally. The clinical pregnant rate, implantation
      rate, endometrial thickness during transferring, as well as the levels of
      estrogen and progesterone 2 weeks after transfer in the two groups were observed
      and compared. RESULTS: The clinical pregnancy rate and implantation rate in the
      treated group were significant higher than those in the control group, 47.37%
      (36/76 cases) vs 32.14% (54/168 cases) and 22.38% (47/210 embryos) vs 16.09%
      (74/460 embryos), respectively (all P <0.05). Difference between the two groups
      in endometrial thickness, levels of estrogen and progesterone showed no
      statistical significance (P > 0.05). CONCLUSION: Chinese herbal medicine could
      enhance the clinical pregnancy rate and implantation rate in the natural cycle of
      FET to certain extent.

PMID- 18822906
TI  - [Clinical observation of bushen er'xian decoction in treating premature ovarian
      failure].
AB  - OBJECTIVE: To observe the therapeutic effect and immune regulatory mechanism of
      Bushen Er'xian Decoction (BED) on patients with premature ovarian failure (POF).
      METHODS: Sixty patients with POF were randomly assigned to two groups in the
      ratio of 2:1, the 40 in the treatment group were treated with BED and the 20 in
      the control group were treated with artificial menstrual cycle therapy. The
      clinical efficacy was observed and the changes of serum reproductive hormone and
      T lymphocytes before and after treatment were observed. RESULTS: The total
      effective rate in the treatment group was 72.5% (29/40 cases), which was higher
      than that in the control group, 45.0% (9/20 cases, P < 0.05). Serum follicle
      stimulating hormone (FSH) and luteinizing hormone (LH) decreased and estradiol
      (E2) increased in both groups after treatment (P <0.05), but the level of FSH was
      lower in the treatment group than in the control group (22.57 +/- 12.49 IU/L vs
      31.10 +/- 14.50 IU/L, P <0.05). CD4 and CD4/CD8 increased, CD8 decreased in the
      treatment group after treatment, showing significant difference as compared with
      those before treatment and with those in the control group after treatment (P
      <0.01). CONCLUSION: BED is favourable for improving POF, being a good remedy with
      better clinical efficacy.

PMID- 18822907
TI  - [Systematic review of randomized controlled trials on preventing and treating
      restenosis after percutaneous coronary intervention with Chinese medicine].
AB  - OBJECTIVE: To evaluate the randomized controlled trials on preventing and
      treating restenosis after percutaneous coronary intervention (PCI) with Chinese
      medicine adopting the principle of evidence-based medicine (EBM). METHODS:
      Pertinent literatures were retrieved roundly, and scored depending on Jadad
      Quality Scale. Meta-analysis was applied on the total effect of outcomes reported
      using RevMan 4. 2 software. Moreover, the sensitivity was analyzed, the
      publication bias was identified with funnel-plot and the adverse reaction of
      medicine was reported. RESULTS: Among the 17 literatures met the inclusion
      criteria, only two double-blinded trials were appraised as high quality. The
      analysis on the recurrence rates of restenosis post-PCI and angina pectoris in
      patients treated with Chinese medicine illustrated that the rates in the
      treatment group were all lower than those in the control group with statistical
      significance (P < 0.01). Sensitivity analysis revealed a relatively stable result
      of the evaluation. Funnel-plot displayed an asymmetrical figure, indicating the
      possible existence of publication bias. CONCLUSION: TCM has definite therapeutic
      effect on preventing and treating restenosis after PCI and reducing the
      recurrence rate of angina pectoris in patients.

PMID- 18822908
TI  - [Relation of phlegm-stasis syndrome with insulin resistance and monocyte
      PPARgamma mRNA expression in patients with coronary heart disease].
AB  - OBJECTIVE: To explore the relation of phlegm-stasis syndrome with insulin
      resistance and monocyte peroxisome proliferator activated receptor-gamma
      messenger ribonucleic acid (PPARgamma mRNA) expression in patients with coronary
      heart disease (CHD). METHODS: Sixty patients with CHD were differentiated into
      three syndrome types, the non-phlegm non-stasis (NN) type, the phlegm congealing
      heart vessel (PC) type and the phlegm-stasis cemented (PS) type. Besides, 20
      healthy volunteers were selected as the normal control. Levels of fasting plasma
      glucose (FPG) and fasting insulin (FINS) were determined and homeostasis model
      assessment of insulin resistance (HOMA-IR) was calculated accordingly. The
      expression of PPARgamma mRNA in the peripheral monocytes was assessed by reverse
      transcriptase-polymerase chain reaction (RT-PCR). RESULTS: Levels of FINS, HOMA
      IR and PPAR-gamma mRNA expression in all CHD patients were higher than in the
      normal control (P <0.01, P < 0.05); comparisons of the three indexes between
      patients of different syndrome types showed that they were higher in PC type and
      PS type than in NN type (P < 0.05 or P <0.01), and the difference between PC type
      and PS type was significant (P < 0.05). CONCLUSION: Changes of insulin resistance
      and PPARgamma mRNA expression in monocytes are possibly one of the mechanisms for
      the development of phlegm-stasis syndrome in CHD.

PMID- 18822909
TI  - [Clinical effect of ligustrazine combined with citicoline for treatment of
      diabetic peripheral neuropathy].
AB  - OBJECTIVE: To assess the clinical efficacy of the therapeutic schema for
      treatment of diabetic peripheral neuropathy (DPN) with ligustrazine and
      citicoline injection in combination. METHODS: Adopting double-centered randomized
      controlled trial, 300 patients were randomly assigned to 3 groups, who were
      treated respectively by ligustrazine plus citicoline (group A), ligustrazine
      alone (group B) and citicoline alone (group C). Clinical efficacy, symptomatic
      integral (SI), electromyogram ( EMG), blood sugar and blood lipids were assessed
      4 weeks after treatment, and the clinical efficacy and SI were assessed at the
      end of 3-month follow-up. RESULTS: After 4-week treatment, improvements of blood
      sugar and blood lipids were seen in all the three groups, showing insignificant
      difference among them (P > 0.05). But the clinical efficacy, improvement of SI
      and EMG in group A were superior to those in group B and C (P < 0.05), while the
      difference between group B and C was insignificant. No severe adverse reaction
      was found. Results at the end of 3-month follow-up showed that the clinical
      efficacy in group A was still better than in the other two groups, so did the SI
      (6.39 +/- 2.04 vs 8.36 +/- 1.17 and 8.05 +/- 1.34, P < 0.05). CONCLUSION: The
      therapeutic schema of using ligustrazine and citicoline in combination is
      effective and safe for improving DPN, and worthy of clinical spreading.

PMID- 18822910
TI  - [Epidemiologic study on basic TCM syndrome in the subhealth population in the
      Zhengzhou area].
AB  - OBJECTIVE: To study the distribution characteristics of clinical manifestation
      and TCM basic syndromes in the subhealth population. METHODS: The investigation
      list for basic syndrome of subhealth used in the study was formulated through
      retrieving a large amount of literatures, referring to principles of
      epidemiology, computer science, mathematics and international metrics, and
      according to the standard denoting figure of GR/T 1.1-2000 and ZY/T001.1-94. The
      data obtained were analyzed by the statistical methods like multiple factor
      analysis and cluster analysis to explore the distribution of main symptoms and
      syndromes in the subhealth condition. RESULTS: The analysis of data from 2,133
      lists showed that in the Zhengzhou area, the main clinical symptoms presented in
      the subhealth population were aversion to cold, fatigue, spontaneous
      perspiration, poor memory, bad-temper, short breath, palpitation, etc.; with the
      syndrome key elements of deficiency, dampness, phlegm, stagnancy, stasis, qi
      stagnation, and body fluid loss; the dysfunction of zang-fu organs was mainly
      observed in Xin, Pi, Shen, Gan, Dan, Wei, Fei, etc.; and the most commonly
      encountered basic syndromes were Xin-Pi deficiency, Xin-Shen deficiency, Gan-qi
      stagnation, Pi insufficiency with dampness stagnation, phlegm-qi cementation,
      Shen-yin deficiency, Shen-yang deficiency, qi insufficiency, Gan-stagnancy
      transforming to fire, damp-heat accumulation, etc. CONCLUSION: The clinical
      manifestation of the subhealth population in the Zhengzhou area is characterized
      by a syndrome composed of a certain main symptom with some other accompanied
      symptoms, the distribution of the basic syndrome is mainly dominated by the
      deficiency syndrome.

PMID- 18822911
TI  - [Synergistic effect of emodin and cyclosporine A on rejective reaction against
      liver graft in rats].
AB  - OBJECTIVE: To evaluate the effect of emodin in combination with cyclosporine A
      (CsA) on rejective reaction against liver graft in rats. METHODS: The LEW-->BN
      orthotopic liver transplantation rat model was used in the study. A total of 48
      rats were divided into 4 groups randomly and equally, after operation they were
      intraperitoneally injected respectively with normal saline (0.5 mL d(-1), group
      A); CsA (10.0 mg kg(-1) d(-1), group B); emodin (50.0 mg kg(-1) d(-1), group C);
      and CsA plus emodin (group D, at the same dose as in B and C). Six rats taken
      from each group were sacrificed on the 8th day after operation to calculate the
      rejection active index (RAI) and hepatocyte apoptosis index (AI). The remainder
      were stopped medication and used for observing the survival time. RESULTS: The
      inter-group comparisons in mean survival time, RAI and AI showed significant
      difference in comparing group A with group B, C and D (P <0.01), and those in
      group D were more obvious than in group B and C (P < 0.05, but showed no
      significant difference between group B and group C (P > 0.05). CONCLUSION:
      Administering of emodin combined with CsA after liver transplantation shows a
      synergistic effect for suppressing acute rejective reaction in rats.

PMID- 18822912
TI  - [Intervening and therapeutic effect of cordyceps mycelia extract on liver
      cirrhosis induced by dimethylnitrosamine in rats].
AB  - OBJECTIVE: To explore the intervening and therapeutic effect of Cordyceps mycelia
      extract (CME) on liver cirrhosis induced by dimethylnitrosamine (DMN) in rats.
      METHODS: Rat liver cirrhosis model was established by peritoneal injection of DMN
      at a dose of 10 microg/kg, once daily in the first 3 days of every week for 4
      successive weeks. Experimental study on CME-intervention was conducted from the
      beginning of modeling to the end of the 4th week, while the CME-treatment
      experiment was carried out from the 4th week of modeling, when terminating the
      modeling factor, to the end of the 8th week, by administering CME at a dose of 0.
      74 g/( kg d) once a day. Animals were killed in batches on the 3rd day, the 2nd
      (T1), 4th (T2), 6th (T3) and 8th (T4) week after modeling, to observe the
      histopathologic change in liver and the immunohistochemical staining of alpha
      smooth muscle actin (alpha-SMA) and collagen type I (Col I), determine the
      content of hydroxyproline (Hyp) in liver, and the liver function was tested as
      well. RESULTS: CME-intervention experiment showed that as compared to those in
      the modeled rats at corresponding time points, in rats at T1 and T2, serum
      alanine aminotransferase (ALT), aspartate aminotransferase (AST) activity and
      total bilirubin (TBIL) content were significantly lower, and albumin (Alb)
      obviously higher; while at T2, Hyp content, ct-SMA and Col I positive expression
      were significantly lower (P < 0.05), the proliferation of collagen fibre
      attenuated. CME-treatment experiment showed that as compared to those in the
      modeled rats at corresponding time points, lower serum ALT, AST activity and TBIL
      content, and higher serum level of Alb were shown in rats at T1; and lower Hyp
      content, liver collagen fibre, and alpha-SMA positive expression were shown at T1
      and T2; while less Col I positive expression at T2 was also shown in them (all P
      < 0.05). CONCLUSION: CME could not only prevent the development of liver
      cirrhosis induced by DMN in rats, but also effectively promote the reversion of
      already formed liver cirrhosis, having a favourable prospect of clinical
      application.

PMID- 18822913
TI  - [Chaotic dynamic process of multiple organs dysfunction syndrome and the
      regulatory function of shenqin liquid on it].
AB  - OBJECTIVE: To explore the chaotic dynamic process of multiple organs dysfunction
      syndrome (MODS) and the regulatory effect of Shenqin Liquid (SQL), a Chinese
      herbal liquid preparation with the action of purging and qi-tonifying. METHODS:
      Eighty SD rats were divided into 4 groups, and were given suspension of zymosan A
      and paraffine (1 mL/kg) by peritoneal injection except for those in the blank
      control group to set up the multiple organs dysfunction syndrome (MODS) model.
      Low and high doses SQL were administered twice at the doses of 30 and 60 g/kg of
      SQL respectively at an interval of 8 h per day before modeling. Serum
      concentration of tumor necrosis factor alpha (TNF-alpha) and nitric oxide (NO) in
      MODS model animals were tested diachronically, eg. 12, 6 h before modeling,
      during modeling, 6 and 12 h after modeling, and then the mathematic models were
      built up with compartment analysis. Lyapunov exponents (LE) of the mathematic
      models were calculated to evaluate their chaotic characteristics of movement and
      the degree of chaos was ascertained with the correlation dimension (CD). RESULTS:
      The serum levels of TNF-alpha and NO were significantly higher than those in the
      bland control group at modeling, 6, and 12 h after modeling (P <0.01), while
      those in the low and high doses of SQL were significantly lower than the model
      group (P <0.01). Moreover, the level of NO in the high dose of SQL was
      significantly lower than that in the low dose group (P <0. 01). CD of TNF-alpha
      movement in the blank control group was 0.803 with the LE less than zero; those
      in the model group was 1. 966 and > 0 respectively; in the low dose and high dose
      SQL treated groups, CD was 0.517 and 0.653 respectively and LE >0. CD of NO
      movement in the blank control group was 0.670 and with LE < 0; in the model
      group, 1.242 with LE > 0; in the low dose SQL group, 0.574 and in the high dose
      SQL group 0.850, and LE <0 in the two groups. CONCLUSION: Under the normal
      physiologic condition, TNF-alpha and NO moved steadily without chaotic
      properties; while under the pathologic condition of MODS, they manifest
      relatively complicated chaotic properties. SQL can intervene the movement of TNF
      alpha and NO, decrease the complexity of their chaotic movement, and make them
      return back to a stable state.

PMID- 18822914
TI  - [Inhibitory effect and acting mechanism of Tongxinluo on IL-1beta-mediated
      coronary intimal hyperplasia and 5-hydroxytryptamine-induced coronary vasospasm
      in small swine].
AB  - OBJECTIVE: To observe the inhibitory effect of Tongxinluo (TXL) on coronary vaso
      spasm in small swine in vivo, and to investigate its possible acting mechanism.
      METHODS: The model of coronary atherosclerosis in 16 male small swines was
      established by left thoracotomy after anesthesia, isolated the sections of left
      anterio-descending branch and proximal end of rotator branch with similar outer
      diameter, and encapsulated them with paper-towel holding 2.5 microg interleukin
      1beta. Two weeks later, the condition of coronary vasospasm induced by catheter
      intra-coronary injection of 5-hydroxytryptamine (5-HT, 10 microg/kg) was observed
      through coronary artery contrast examination. The 12 swines with successfully
      formed coronary vaso spasm were randomly divided into 2 groups, the TXL group and
      the control group. They were fed with special diet, but TXL 1 g/(kg d) was
      administered additionally to the TXL group for 4 weeks. The observation on
      coronary vasospasm was repeated 1 week after discontinuation of TXL treatment,
      then the animals were sacrificed, their vascular sections enclosed with IL-1beta
      was taken to conduct the pathologic examination and to detect the expressions of
      Rho kinase mRNA and its substrate myosin- binding subunit phosphorylation (MBS-P)
      by RT-PCR and Western blot method. RESULTS: Coronary artery contrast showed that
      local coronary stenosis occurred in the 12 model swines to different extents (20%
      - 30%, and vascular spasm on them could be induced by 5-HT. At the time of
      repeating examination, 11 vascular sections in the control group still maintain
      their positive spasm reaction to 5-HT, but only 2 in the TXL group did so, the
      reaction turned to negative in 1 and 10 in the two groups respectively.
      Pathological examination showed that different degrees of macrophage aggregation
      could be found in both groups. The degree of lumen stricture and endometrial
      hyperplasia in the TXL group was obviously attenuated than those in the control
      group. The expressions of Rho kinase mRNA and MBS-P in the control group were up
      regulated obviously. As compared with those in the control group, they were
      inhibited significantly in the TXL group, as (71.5 +/- 2.4) vs (98.2 +/- 7.7)%
      and 16,633 +/- 1,390 vs 25,818 +/- 4,745, respectively (all P < 0.05).
      CONCLUSION: TXL could obviously inhibit the coronary intimal hyperplasia mediated
      by IL-1beta and coronary vasospasm induced by 5-HT, one of its mechanisms is
      possibly the inhibition on the intracellular Rho kinase mRNA expression in the IL
      1beta enclosed vascular section to decrease the level of MBS-P.

PMID- 18822915
TI  - [Effect of tanshinone II A on angiotensin receptor in hypertrophic myocardium of
      rats with pressure over-loading].
AB  - OBJECTIVE: To explore the molecular biological mechanism of tanshinone II A (TSN)
      in preventing hypertensive left ventricular hypertrophy (HLVH) through studying
      the effects of TSN on angiotensin receptor (ATR) expression and free calcium ion
      ([Ca2+]i) in rats with hypertrophic myocardium caused by abdominal aorta
      constriction. METHODS: SD rats were established into HLVH model by abdominal
      aorta constriction operation, they were randomly divided into the model group,
      the three treated groups treated respectively with intra peritoneal injection of
      low dose TSN (10 mg/kg) and high dose TSN (20 mg/kg) and gastrogavage of
      Valsartan (10 mg/kg) once a day 4 weeks after modeling. Besides, 8 sham-operated
      SD rats were set up as the control group. Eight weeks later, rats' caudal
      arterial pressure was measured, and their hearts were taken for measuring the
      left ventricular mass index (LVMI) and myocardial fiber diameter (MFD) by HE
      stain of the pathological section. Moreover, the mRNA and protein expressions of
      AT1 and AT2 receptors in the left ventricular tissue were detected by RT-PCR and
      Western blot, and [Ca2+]i concentration was determined with laser-scanning
      confocal microscope. RESULTS: (1) The elevated blood pressure in the TSN treated
      groups, either high or low dose, remained unchanged, significantly higher than
      that in the control group and the Valsartan treated group (P < 0.01, P < 0.05).
      (2) LVMI and MFD in the three treated groups were significantly lower than those
      in the model group (P <0.01), respectively, although they were higher than those
      in the control group (P <0.05). (3) The mRNA and protein expressions of AT1
      receptor were obviously lower in the three treated groups than those in the model
      groups (P < 0.05); but the lowering was more significant in the valsartan treated
      group (P < 0.05). (4) The mRNA and protein expressions of AT2 receptor were
      significantly higher in the Valsartan treated group as compared with other groups
      (P < 0.05), while the difference among the other groups showed no statistical
      significance (P > 0.05). (5) The elevated (Ca2+]i concentration in hypertrophic
      myocardium after modeling was significantly lowered after treatment in the three
      treated groups (P < 0.05), but the lowering in the high TSN treated group was
      more significant than that in the Valsartan treated group (P <0.05). CONCLUSION:
      The inhibition of TSN on myocardial hypertrophy is blood pressure independent,
      its mechanism is possibly related with the inhibition on AT1R gene expression and
      the blocking of free calcium ion influx in cardiac muscle cells. AT2 receptor may
      participate the effect of Valsartan in lowering blood pressure and reversing
      myocardial hypertrophy.

PMID- 18822916
TI  - [Effect of nano-liposome sustained elemene in inducing cell apoptosis of C6
      glioma].
AB  - OBJECTIVE: To study the effect of nano-liposome sustained elemene in inducing
      cell apoptosis of C6 glioma and to explore its influence on the expression of
      caspase-3 gene. METHODS: C6 glioma cells were cultured in medium with the same
      amount of nano-liposome sustained elemene and common elemene respectively, also
      in blank medium for control. The status of cell apoptosis was determined by flow
      cytometry at 0, 48 h and 72 h, and the expression of Caspase-3 protein was
      measured simultaneously by immunohistochemistry assay. RESULTS: Marked apoptosis
      presented in cells cultured in the medium with nano-liposome sustained elemene or
      common elemene at 48 h and 72 h, with the apoptotic rate significantly higher
      than that in the control. At the same time, Caspase-3 protein expression raised
      significantly in cells cultured in medium with either kinds of elemene, showing
      significant difference when compared with that in the control. CONCLUSION:
      Elemene has significant apoptosis promoting and Caspase-3 protein expression
      inducing effect on C6 glioma cells, which could be facilitated by nano-liposome
      bearing.

PMID- 18822917
TI  - [Effect of sodium ferulate on hemodynamics in hepatic cirrhosis patients with
      portal hypertension].
AB  - OBJECTIVE: To observe the effect of sodium ferulate on the hemodynamics of
      hepatic cirrhosis patients. METHODS: Eighty-two hepatic cirrhosis patients were
      randomly assigned to two groups, the 27 patients in the control group were
      treated by conventional liver protecting therapy, and the 55 patients in the
      treated group were treated with sodium ferulate besides the conventional therapy.
      The therapeutic course for both groups was two weeks. The following indexes were
      measured before treatment and two weeks after treatment respectively: inner
      diameter of portal vein (PV), inner diameter of splenic vein (SPV), maximum
      portal vein flow rate (PVX), maximum splenic vein flow rate (SPVX), portal vein
      blood flow (QPV) and endothelin-1 (ET-1) concentration. The adverse effect was
      observed meanwhile. RESULTS: In the treated group after treatment, levels of PV,
      SPV and ET-1 decreased (P < 0.01), PVX and SPVX increased significantly (P <
      0.01), but QPV was unchanged; while no significant change of all the indexes was
      found in the control group (P > 0.05). Further analysis showed that in the
      treated group, PV, SPV and ET-1 decreased significantly in patients of Child
      grade A and B (P <0. 01), but QPV changed insignificantly (P > 0.05, and all
      indexes were unchanged in patients of Child grade C (P > 0.05). CONCLUSION:
      Sodium ferulate can effectively lower the pressure of portal vein in hepatic
      cirrhosis patients without any influence on the blood flow of portal vein, the
      effect is more significant on patients of Child grade A and B.

PMID- 18822918
TI  - [Effect of umbilical sticking therapy with qitou xiaogu plaster in treating liver
      cirrhosis patients with portal hypertension].
AB  - OBJECTIVE: To observe the effect of umbilical sticking therapy (UST) with Qitou
      Xiaugu Plaster (QXP) on hemodynamics of portal system in patients with liver
      cirrhosis. METHODS: One hundred and twenty patients of liver cirrhosis with
      portal hypertension were assigned to two groups. On the basis of conventional
      therapy, UST was applied in the 66 patients in treated group, which was exchanged
      once every 3 days with an interval of 1-day rest. The 54 patients in the control
      group were orally administered with propanolol. The therapeutic course for both
      groups was 1 month. Before and after treatment, the hemodynamic changes in portal
      or splenic veins were observed by color Doppler ultrasonograph, and the changes
      of liver function, blood coagulation and patients' subjective symptoms were
      observed as well. RESULTS: After treatment, portal vein diameter and splenic vein
      diameter significantly decreased (P < 0.05, portal venous flow velocity and
      splenic venous flow velocity apparently increased (P < 0.05), and portal venous
      flow apparently decreased in both groups (P < 0.05), while no significant change
      was found in the splenic venous flow (P > 0.05). The liver function and blood
      coagulation indexes in both groups were improved. The improvement of clinical
      symptoms in the treated group was superior to that in the control group.
      CONCLUSION: UST with QXP could decrease the portal vein pressure in a short time,
      with the therapeutic effect comparable to propanolol, and with no adverse
      reaction.

PMID- 18822919
TI  - [Effect of retention enema with combination of compound glutamine entero-soluble
      capsule and glucocorticoids for treatment of ulcerative colitis].
AB  - OBJECTIVE: To observe the therapeutic effect and safety of retention enema with
      compound glutamine entero-soluble Capsule (CGC) on active ulcerative colitis
      (UC). METHODS: One hundred and sixty-eight patients with active UC were randomly
      assigned to the treatment group (86 patients) and the control group (82
      patients). Besides the basic treatment of oral taking salicylazosulfapyridine or
      mesalazine, they were treated by retention enema with predisolone plus
      metronidazole injection. In addition, the patients in the treatment group were
      treated by retention enima with GGC and orally took CGC, 0.8 g each time, thrice
      a day. The efficacy of treatment and the changes in the principal symptoms 2
      months after treatment were evaluated. RESULTS: The total effective rate in the
      treatment group was 94.2% (81/86 cases), and that in the control group was 82.9%
      (68/82 cases), the difference between the two groups was significant (P <0. 05).
      The symptoms of hemafecia and abdominal pain were improved, the disease active
      index (DAI) was lowered after treatment in both groups (P <0.01), but the
      improvement of hemafecia, time of disappearance of mucous bloody stool and
      decrease of DAI in the treatment group were superior to those in the control
      group (P <0.05 or P <0.01). No adverse reaction was found in all patients.
      CONCLUSION: The retention enema with glucocorticoid plus metronidazole combined
      with CGC shows an immediate effect obviously superior to that treated with
      glucocorticoids and metronidazole alone, and with no adverse reaction.

PMID- 18822920
TI  - [Effect of busui shengxue granule on serum tyrosine kinase 3 ligand and
      fibronectin in patients with chronic aplastic anemia].
AB  - OBJECTIVE: To observe the clinical effect of Busui Shengxue Granule (BSG) in
      treating chronic aplastic anemia (CAA) and the changes of serum fibronectin (Fn)
      level and expression of FMS-like tyrosine kinase 3 ligand (FL). METHODS: Sixty
      eight patients with CAA were assigned to two groups. The 35 patients in the test
      group were treated with BSG and the 33 in the control group by Zaizhang Shengxue
      Tablet. Levels of Fn and FL were determined before and after 6-month treatment by
      enzyme linked immunosorbent assay. RESULTS: The clinical effective rate in the
      test group was 74.3% (26/35 cases), and that in the control group 48.5% (16/33
      cases), the difference between the two groups was significant (P <0.05). In the
      test group, patients of yang-deficiency type showed an effect superior to that of
      yin-deficiency type, 93.8% (15/16 cases) vs 57.9% (11/19 cases, P < 0.05). High
      expression manners of Fn and FL were shown in all CAA patients, the high
      expressions of both were lowered to some extent after treatment, but the
      improvement in the test group was better than that in the control group (P
      <0.05), and the deviation was more liable to be corrected in patients of Shen
      yang deficiency type than that in patients of Shen-yin deficiency type.
      CONCLUSION: BSG is better than Zaizhang Shengxue Tablet in clinical effect and
      improving the CAA related adhesive molecules, Fn and FL, suggesting that it is an
      effective remedy for preventing and treating CAA, with its curative effect more
      significant on patients of yang-deficiency type than that on patients of yin
      deficiency type.

PMID- 18822921
TI  - [Discussion on some basic academic problems in research and development of
      treatment based on syndrome differentiation].
AB  - To implement treatment depending on syndrome differentiation, namely, the
      syndrome dependent therapy (SDT), is the characteristics of Chinese medicine,
      also an important field for TCM researches and development in the contemporary
      era. This paper summarized the common academic problems in this field, involving
      the relationship between syndrome and disease, body constitution, four diagnostic
      methods and SDT, the mechanisms of diseases, syndromes and SDT, as well as the
      relationship between SDT and Western medicine. The thinking path and
      recommendation for solution were proposed as well.

PMID- 18822922
TI  - [Current status of study on impacts of Chinese herbal drugs and their
      preparations on pharmacokinetics].
AB  - Since Chinese herbal drugs and their preparations were usually applied in
      combining with digoxin in modern clinical practice, high attention was
      accordingly widely paid to their impacts on the pharmacokinetics of digoxin. The
      researches in the recent years dealing with this topic were reviewed in the
      paper, involving the Chinese herbs, including Radix Ginseng, Radix Salviae
      Miltiorrhizae, Venenum Bufonis, Folium Seu Cortex Nerii Indici, St John's wort,
      Fructus Crataegi, and Semen Ginkgo, as well as the Chinese herbal preparations
      including Shengmai Injection, Milkvetch Injection, Liushen Pill, Kyushin, and
      Di'ao Xinxuekang, etc.

PMID- 18822923
TI  - [Progress on study of clinical application of xinhuang tablet on orthopedic
      diseases].
AB  - By retrieval of medical periodicals published in the recent 23 years, 155 papers
      concerning Xinhuang Tablet were searched, among them 28 were dealing with its
      clinical application in orthopedics disease, involving gouty arthritis, soft
      tissue injury, osteoarthritis, ankylosing spondylosis, rheumatoid arthritis, etc.
      Besides the traditional oral administration mode, Xinhuang Tablet may be used
      externally for local absorption through transcutaneous manner by mixing with some
      adjuvant as honey, vinegar, wine, and egg white.

PMID- 18822924
TI  - Psychological effects of earthquakes in children: prospects for brief behavioral
      treatment.
AB  - BACKGROUND: Treatment of child earthquake survivors is a relatively less
      investigated issue in disaster research. A review of the evidence on the mental
      health effects of earthquakes, risk factors, and findings from treatment studies
      may provide useful insights into effective treatment of traumatized children.
      DATA SOURCES: Studies of child and adolescent earthquake survivors included the
      PILOTS database (electronic index for literature on psychological trauma) and
      relevant evidence from various studies of adult earthquake survivors. RESULTS:
      Evidence points to elevated rates of posttraumatic stress disorder (PTSD),
      depression, and earthquake-related fears in children and adolescents. Traumatic
      stress appears to be mediated by loss of control over fear induced by exposure to
      unpredictable and uncontrollable earthquakes. This implies that interventions
      enhancing sense of control over fear are likely to be most effective. Recent
      studies indeed show that a control focused behavioral treatment (CFBT) involving
      mainly encouragement for self-exposure to feared situations is highly effective
      in facilitating recovery from earthquake trauma. Evidence also suggests that CFBT
      can be delivered through booklets and similar media. CONCLUSIONS: Pilot studies
      suggest that CFBT has promise in effective treatment of PTSD in children. Further
      research is needed to confirm these preliminary findings and to develop self-help
      tools for children.

PMID- 18822925
TI  - An update in prevention and treatment of pediatric obesity.
AB  - BACKGROUND: Obesity prevalence is growing as well as its severity with increasing
      morbidity and mortality. This "globesity" also affects developing countries where
      under nutrition and stunting frequently coexist with overweight and obesity. One
      third of obese adults began to be so in the pediatric ages. There are two main
      types of prevention: general one representing greater actions from health
      authorities and the individual one carried out by the pediatrician and the
      patient at risk. Once the state of obesity is reached (relative body mass index,
      rBMI >121%) the longer lasting care becomes more complex and frequently
      unsuccessful. The treatment of obesity is aimed to care for the present and
      silent disorders and for preventing its further tracking to adulthood. DATA
      SOURCES: Identification of pediatric population at risk which is the one with an
      rBMI of 111%-120% plus other risk factors. Specific individual actions include
      reduction of food intake, increase of energy expenditure, involvement of parents,
      and the child-adolescent himself in the prevention. Therapy is based on some
      principles plus the important medical and emotional approach. RESULTS: A Cochrane
      study based on only 10 appropriate studies showed a predominant poor efficacy of
      the undergone preventive action. Treatment guides are presented after our own
      experience with a group of 400 kids with an average follow-up of 7 years and
      other individual prevention studies. CONCLUSIONS: Involving motivated
      pediatricians with a minimum of time for visits and better follow-up in the frame
      of a general national preventive programme could be a rational outcome. Treatment
      of obesity should never be postponed whatever the clinical care is.

PMID- 18822926
TI  - Network in pediatric rheumatology: the example of the Pediatric Rheumatology
      International Trials Organization.
AB  - BACKGROUND: Pediatric rheumatic diseases (PRDs) are rare conditions associated
      with significant sequelae affecting the quality of life and long-term outcome.
      The research aimed at studying new therapeutic approaches is difficult because of
      logistic, methodological and ethical problems. DATA SOURCES: To address these
      problems, two international networks, the Pediatric Rheumatology Collaborative
      Study Group (PRCSG) and the Pediatric Rheumatology International Trials
      Organization (PRINTO) were established. The two networks share the goal to
      promote, facilitate and conduct high quality research for PRDs. RESULTS: The
      PRINTO and PRCSG networks have standardized the evaluation of response to therapy
      in juvenile idiopathic arthritis (JIA), juvenile systemic lupus erythematosus,
      and juvenile dermatomyositis, drafted clinical remission criteria in JIA, and
      provided cross-cultural adapted and validated quality of life instruments
      including the Childhood Health Assessment Questionnaire and the Child Health
      Questionnaire into 32 different languages. In this paper we reviewed how the
      networks of the PRINTO and PRCSG have created the basic premises for the best
      future assessment of PRDs. CONCLUSIONS: The PRINTO and PRCSG networks can be
      regarded as a model for international cooperation or collaboration in other
      pediatric subspecialties.

PMID- 18822927
TI  - Hypercapnia and hypocapnia in neonates.
AB  - BACKGROUND: The arterial partial pressure of carbon dioxide (PaCO2) represents
      the balance between CO2 production and consumption. Abnormal increase or decrease
      in PaCO2 can affect the body's internal environment and function. Permissive
      hypercapnia has aroused more attention as a novel ventilatory therapy. The aim of
      this study was to elucidate the effects of hypercapnia and hypocapnia on the
      functions of such neonatal organs as the lung and brain. DATA SOURCES: The PubMed
      database was searched with the keywords "hypocapnia", "hypercapnia" and
      "newborn". RESULTS: Hypocapnia is a risk factor for potential damage to the
      central nervous system, such as periventricular leukomalacia, intraventricular
      hemorrhage, cerebral palsy, cognition developmental disorder, and auditory
      deficit. Hyperventilation can lessen pulmonary artery hypertension to certain
      extent, but hypocapnia can aggravate ischemia/reperfusion-induced acute lung
      injury. Severe hypercapnia can induce intracranial hemorrhage, even consciousness
      alterations, cataphora, and hyperspasmia. Permissive hypercapnia can improve lung
      injury caused by diseases of the respiratory system, lessen mechanical
      ventilation-associated lung injury, reduce the incidence of bronchopulmonary
      dysplasia and protect against ventilation-induced brain injury. In addition,
      permissive hypercapnia plays a role in expanding cerebral vessels and increasing
      cerebral blood flow. CONCLUSIONS: Severe hypercapnia and hypocapnia can cause
      neonatal brain injury and lung injury. Permissive hypercapnia can increase the
      survival of neonates with brain injury or respiratory system disease, and lessen
      the brain injury and lung injury caused by mechanical ventilation. However, the
      mechanism of permissive hypercapnia needs further exploration to confirm its
      safety and therapeutic utility.

PMID- 18822928
TI  - Molecular epidemic features and variation of rotavirus among children with
      diarrhea in Lanzhou, China, 2001-2006.
AB  - BACKGROUND: Human rotavirus (HRV) is the most common pathogen causing severe
      diarrhea among infants and young children worldwide. This study aims to
      understand rotavirus epidemiology and its variation in the period of 2001-2006 in
      Lanzhou, Gansu Province, China, and to provide an epidemiological basis for the
      development of rotavirus vaccine. METHODS: A total of 1019 stool specimens were
      collected from patients with acute diarrhea admitted to the First Hospital of
      Lanzhou University from 2001 to 2006, who were younger than 5 years old. Dako
      IDEIATM kits were used for detection of rotavirus, and RT-PCR was performed for
      determination of G serotype and P genotype of the rotavirus. RESULTS: Rotavirus
      was present in 51.6% (526) of the 1019 specimens. G serotype identified G3 at
      40.9%, G2 14.6%, G1 22.2% and G9 1.9%. Mixed-G infection was observed in 4.4% and
      non-typeable infection 16.0%. P genotype was observed in 372 samples, of which
      P[8] accounted for 186 cases (50.0%), P[4] 72 cases (19.4%), mixed-P infection 2
      cases (0.5%), and non-typeable cases 112 (30.1%). G3 was the most prevalent G
      serotype found in this study from 2001 to 2004, G2 was the most prevalent G
      serotype (34.4%) from 2004 to 2005, and G1 (61.5%) was the most prevalent strain
      from 2005 to 2006. G9 was detected in 10 cases (1.9%) and G4 was not detected
      during this 5-year period. P[8] was the most prevalent P genotype found over the
      5 consecutive years of this study, although there was a significant transition of
      P genotype from 2004 to 2005 with P[4] (45%) identified as the predominant P
      genotype, followed by P[8] (22.1%). The predominant G-P combination was P[8]G1
      (33.6%), followed by P[8]G3 (32.1%) and P[4]G2 (17.2%). Rotavirus diarrhea
      admissions peaked between October and December. Continuous surveillance showed
      that the incidence rate of rotavirus was the highest in infants aged 6-23 months,
      averaging 11.0-11.9 months. CONCLUSIONS: Five years of continuous surveillance
      showed that rotavirus remains the most significant viral agent causing diarrhea
      hospitalization among children under 5 years old in Lanzhou, China although the
      predominant strain of rotavirus varies between years. Mixed-G serotype infection
      also appears to occur at a relatively high rate in Lanzhou.

PMID- 18822929
TI  - The relationship between drug treatment and the clinical characteristics of
      febrile seizures.
AB  - BACKGROUND: Drugs such as theophylline, antihistamines, and antiallergics with
      anti-histaminic actions have been shown to induce febrile seizures. The
      relationship between febrile seizures and medications has not been actively
      investigated. The present study aimed to investigate the relationship between the
      clinical characteristics of febrile seizures and the use of medications. METHODS:
      Two hundred and sixty-five children treated at our emergency room due to febrile
      seizures were studied to investigate the relationship between the clinical
      characteristics of febrile seizures, such as the type and duration of
      convulsions, and the drug treatment. RESULTS: The duration of convulsions was
      longer among children who took theophylline and antihistamines than among
      children who did not take these medications. Of the antihistamines, mequitazine
      did not prolong the duration of convulsion. CONCLUSIONS: Theophylline should not
      be used in febrile children, particularly infants. Cautions should be taken in
      using histamine H1 antagonists in young infants because such drugs could
      potentially disturb the anticonvulsive central histaminergic system. However,
      mequitazine appears to be a suitable antihistamine for use in children with
      febrile seizures, since it does not prolong convulsions.

PMID- 18822930
TI  - Multidisciplinary behavioural treatment of fecal incontinence and constipation
      after correction of anorectal malformation.
AB  - BACKGROUND: Fecal incontinence and constipation are major problems after
      correction of anorectal malformation (ARM), caused not only by the somatic
      defects but also by a psychosomatic dysfunction of defecation. To better release
      patients from this dysfunction we offered a multidisciplinary, psycho- and
      physiotherapeutic therapy according to an approach developed in Nijmegen
      (Netherlands). We herein summarize the preliminary results to evaluate whether
      the approach can be adopted with similar success. METHODS: Since January 2002
      multidisciplinary behavioural treatment (MBT) has been offered to children above
      3 years of age and suffering from fecal incontinence and constipation after
      surgical correction of ARM in our department or elsewhere. Prerequisites included
      no anal stenosis, regulation of stool consistency, and a suitable defecation
      diary over 2 weeks. MBT contained regular consultations by a pediatric
      psychologist and a physiotherapist, teaching the child to establish a regular
      defecation pattern and how to push while relaxing the pelvic floor. The entry-
      and post-treatment situation was prospectively monitored by means of defecation
      and constipation scoring systems. RESULTS: Complete data were available in 10
      patients (9 males, 1 female) with high (8 patients) and low (2) forms of anal
      atresia initially, who finished MBT 2-36 months ago (mean: 13 months). The
      average amount of stool reaching the toilet was 27% before and 90% after therapy.
      Clean days were absent before, reaching 3.7 days on average after therapy.
      Constipation was present in 6 patients before (3 of them on enemas) and in 2
      after therapy (no enemas needed). The duration of MBT was 7 months on average,
      range 3-23 months, with 8-9 sessions per patient, each lasting 60-90 minutes. An
      observation period of 7 months after treatment confirmed stable results. MBT
      turned out to improve body-consciousness and self-confidence. CONCLUSIONS: MBT is
      effective in reducing incontinence and constipation in patients after ARM. It
      helps the children and their families to relieve psychosocial stress. The
      approach can be successfully adopted, if a team of committed specialists is
      available and sufficient compliance of patients and families is given.

PMID- 18822931
TI  - Peak expiratory flow rate of rural school children from Wardha district,
      Maharashtra in India.
AB  - BACKGROUND: Peak expiratory flow rate (PEFR) recording is an essential measure in
      the management and evaluation of asthmatic children. The PEFR can be measured by
      a simple instrument--peak expiratory flow meter. The aim of this study was to
      determine the normal PEFR in rural school children from Wardha district of
      Maharashtra state, India. METHODS: The PEFR was measured in 1078 healthy rural
      school children, living in Wardha district, Maharashtra using the Mini-Wright
      peak flow meter. All measurements were obtained in a standing position and the
      best out of three trials was recorded. Anthropometric measurements, weight,
      height, and mid-upper-arm circumference (MAC) were recorded, and body surface
      area (BSA) and body mass index (BMI) were calculated. RESULTS: Positive
      correlation was seen between age, height, weight and PEFR. The regression
      equations for PEFR were determined for boys and girls separately. The boys had
      higher values than the girls at all heights. The prediction equation for PEFR
      based on height was PEFR = 3.64 height (cm) - 257.86 (R=0.47, R2=0.22) for
      female; PEFR = 4.7 height (cm) - 346.51 (R=0.62, R2 =0.38) for male. CONCLUSION:
      PEFR is a reliable measurement, which can be used routinely and regularly in
      rural areas for assessment of airway obstruction and prediction formula derived
      for use in this population.

PMID- 18822932
TI  - Do high blood glucose peaks contribute to higher HbA1c? Results from repeated
      continuous glucose measurements in children.
AB  - BACKGROUND: HbA1c levels are influenced by the glycemic control of previous 2-3
      months. Sometimes patients have surprisingly low HbA1c in spite of many correctly
      measured high blood glucose values, which is difficult to explain. As glucose
      sensors give an objective picture based on glucose readings several times per
      minute over 24 hours, we used the area under the curve (AUC) of such subcutaneous
      glucose profiles to evaluate their relationship with HbA1c. METHODS: Thirty-two
      patients were randomized into two study arms, one open and the other blinded.
      Both arms had 8 pump users and 8 patients with multiple daily injections (MDI).
      After three months the two arms crossed over. Both study arms wore a continuous
      glucose monitoring system (CGMS) for 3 days every 2 weeks. HbA1c was determined
      before and after each 3-month study period. RESULTS: There was no relationship
      between HbA1c and s.c. glucose AUC or between HbA1c and the number of peaks >15.0
      mmol/L when all CGMS profiles during the 6 months were taken together. Children
      on MDI showed a positive relationship between HbA1c and AUC (P<0.01) as well as
      the number of peaks (P<0.01). Children with a negative relationship between HbA1c
      and AUC generally had fewer fluctuations in blood glucose values, whereas
      children with a positive relationship had wide fluctuations. between s.c. glucose
      AUC and HbA1c, the results indicate that wide blood glucose fluctuations may be
      related to high HbA1c values. Therefore, complications and therapeutic
      interventions should aim at reducing such fluctuations. CONCLUSIONS: Although
      there was no relationship between s.c. glucose AUC and HbA1c, the results
      indicate that wide blood glucose fluctuations may be related to high HbA1c
      values. Therefore, complications and therapeutic interventions should aim at
      reducing such fluctuations.

PMID- 18822933
TI  - Birth weight and adult lung function: a within-pair analysis of twins followed up
      from birth.
AB  - BACKGROUND: The aim of the study was to evaluate whether there is any association
      between intrauterine growth and later lung function or bronchial reactivity in
      early adulthood in line with Barker's hypothesis. METHODS: Nineteen twin pairs
      with disproportionate intrauterine growth pattern were followed up from birth:
      either one of the pairs had intrauterine growth retardation (birth weight <2 SD)
      or the within-pair birth weight difference was >1.3 SD. Flow-volume spirometry,
      followed by isocapnic hyperventilation of cold air, was performed at the ages of
      8-16 and 14-22 years in 1993 and 1999. Wilcoxon's matched-pairs analysis was used
      to compare smaller and larger twin pairs. RESULTS: In 1993, there were no
      significant differences between the groups in either spirometry or cold air
      challenge. In 1999, such a difference was found in forced expiratory volume %
      (FEV%) and forced expiratory flow (FEF) at 25%-75%, the smaller twin pairs having
      lower values. In 1993, nine subjects reacted to cold air (>9% decrease in FEV in
      1 second). In 1999, only four subjects reacted to cold air, and they all belonged
      to the group of smaller twins (P=0.04). CONCLUSION: Lung function evaluated by
      FEV% and FEF25-75 was lower and responses to cold air were more common at the
      median age of 16 years in twins with impaired intrauterine growth.

PMID- 18822934
TI  - Diffuse cavernous hemangioma of the spleen with Kasabach-Merritt syndrome
      misdiagnosed as idiopathic thrombocytopenia in a child.
AB  - BACKGROUND: Most cavernous hemangiomas in the spleen are small lesions that are
      found incidentally and patients usually present with no symptoms. Imaging is able
      to detect the lesions that are considered as diagnostic evidence. But some
      patients with diffuse cavernous hemangioma may present with anemia,
      thrombocytopenia, coagulopathy and bleeding, which might be misdiagnosed as
      idiopathic thrombocytopenia with disseminated intravascular coagulation (DIC).
      Splenectomy is the most effective therapy for diffuse cavernous hemangiomas with
      symptoms. METHODS: The history, imaging results, pathologic findings, diagnosis
      and treatment of a 34-month-old boy with severe petechiae were reviewed. RESULTS:
      The boy was diagnosed as having refractory idiopathic thrombocytopenia (ITP)
      because of low platelet count and bleeding at a local hospital. He had no
      response to a full-dose of corticosteroid and a high-dose of immunoglobulin (2
      g/kg). Huge splenomegaly and DIC were found after 7 months. Diffuse cavernous
      hemangioma of the spleen was highly suspected, but it was not confirmed by B
      ultrasound, enhanced CT or MRI. DIC and bleeding were solved by low molecular
      weight heparin, supplement of fibrinogen and prothrombin complex. A diffuse
      cavernous hemangioma involving the whole spleen was confirmed pathologically
      following a successful splenectomy. The boy recovered completely without any
      complication after the operation. CONCLUSIONS: Diffuse cavernous hemangioma of
      the spleen should be differentiated from ITP associated with splenomegaly.
      Radiological and overall physical examination should be emphasized for refractory
      ITP cases.

PMID- 18822935
TI  - Tension pneumocranium in childhood trauma.
AB  - BACKGROUND: To report a case of fatal tension pneumocephalus in a 9-year-old boy
      following a severe motor vehicle accident. METHODS: A young boy with a serious
      closed head injury was resuscitated in the emergency room and underwent CT scan
      of the head and orbits. RESULTS: The CT-scan revealed a fracture of the orbital
      roof with extensive bilateral pneumocephalus. CONCLUSIONS: A high index of
      suspicion for tension pneumocephalus is required in patients with severe head
      injuries presenting with periorbital swelling and perioccular trauma. A prompt CT
      scan and neurosurgical intervention are indicated.

PMID- 18822936
TI  - A rare cutaneous sign of occult spinal dysraphism with tethered spinal cord.

PMID- 18822937
TI  - Response to traumatic brain injury neurorehabilitation through an artificial
      intelligence and statistics hybrid knowledge discovery from databases
      methodology.
AB  - PURPOSE: Develop a classificatory tool to identify different populations of
      patients with Traumatic Brain Injury based on the characteristics of deficit and
      response to treatment. WORK METHOD: A KDD framework where first, descriptive
      statistics of every variable was done, data cleaning and selection of relevant
      variables. Then data was mined using a generalization of Clustering based on
      rules (CIBR), an hybrid AI and Statistics technique which combines inductive
      learning (AI) and clustering (Statistics). A prior Knowledge Base (KB) is
      considered to properly bias the clustering; semantic constraints implied by the
      KB hold in final clusters, guaranteeing interpretability of the resultis. A
      generalization (Exogenous Clustering based on rules, ECIBR) is presented,
      allowing to define the KB in terms of variables which will not be considered in
      the clustering process itself, to get more flexibility. Several tools as Class
      panel graph are introduced in the methodology to assist final interpretation.
      WORK RESULTS: A set of 5 classes was recommended by the system and interpretation
      permitted profiles labeling. From the medical point of view, composition of
      classes is well corresponding with different patterns of increasing level of
      response to rehabilitation treatments. DISCUSSION: All the patients initially
      assessable conform a single group. Severe impaired patients are subdivided in
      four profiles which clearly distinct response patterns. Particularly interesting
      the partial response profile, where patients could not improve executive
      functions. CONCLUSIONS: Meaningful classes were obtained and, from a semantics
      point of view, the results were sensibly improved regarding classical clustering,
      according to our opinion that hybrid AI & Stats techniques are more powerful for
      KDD than pure ones.

PMID- 18822938
TI  - Comparative study of interleukin 1ALFA and interleukin 6 concentrations in serum
      specimens detected by ELISA.
AB  - Interleukin 1 (IL-1) contains two proteins, which are the products of distinct
      genes, but which recognize the same cell surface receptors. In the liver, IL-1
      initiates the acute phase response resulting in an increase in hepatic protein
      synthesis and decreased albumin production IL-1 also plays an important role in
      immune functions, having effects on macrophages/monocytes, T lymphocytes, B
      lymphocytes, NK cells, and LAK cells. Interleukin-6 (IL-6) is a cytokine that
      regulates immune responses. We analyzed total 160 serum specimens of patients
      from Clinical Center University of Sarajevo with different inflammatory diseases
      by ELISA method on interleukins: IL-1alfa and IL-6. Tests that we performed with
      IL-lalfa and IL-6 by ELISA method confirmed that serum specimens with IL-6 ELISA
      showed increased values of tested specimens, than the lowest standard and blank.
      We had average levels of IL-1alfa 3.7 pg/ml which was below the level of the
      lowest standard. All obtained results were in accordance with the results in IBL
      protocol for blank and lowest standard values, as well as the average levels of
      serum specimen values.

PMID- 18822939
TI  - Anthropometric indices and gastro-esophageal reflux disease in adult population
      in Tirana, Albania.
AB  - PURPOSE: To assess the association of Gastro-Esophageal Reflux Disease (GERD)
      with anthropometric indices [body mass index (BMI) and waist-to-hip ratio (W/H)]
      in the adult population of Tirana, the Albanian capital. WORK METHOD: A case
      control study was conducted in Tirana in 2005-2007 including 126 consecutive
      patients diagnosed with GERD at the Endoscopy Unit of the University Hospital
      Center (77 men aged 54.95 +/- 14.58 years; 49 women aged 50.33 +/- 15.42 years),
      and 252 GERD-free hospital based controls (150 men aged 54.55 +/- 6.78 years; 102
      women aged 50.30 +/- 11.00 years; 84% response). A structured questionnaire
      included information about socioeconomic characteristics and behavioral factors.
      Physical examination included measurement of height and weight, and waist and hip
      circumferences. Multivariable-adjusted binary logistic regression was used to
      assess the independent associations of anthropometric indices with GERD. WORK
      RESULTS: GERD was positively associated with BMI (age-adjusted OR = 2.49, 95% CI
      = 1.40-4.43 for BMI > or = 30 vs.< 30), but less so with W/H (OR = 1.33, 95% CI =
      0.85-2.09 for values above cutoff vs. values below cutoff). Upon adjustment for
      socioeconomic characteristics and behavioral factors, the association with BMI
      persisted strongly (OR = 2.12, 95% CI = 1.13-3.98), whereas the relationship with
      W/H was slightly attenuated (OR = 1.22, 95% CI = 0.73-2.02). DISCUSSION: Our
      findings indicate that BMI is a strong predictor of symptomatic GERD, independent
      of animal fat intake, smoking, alcohol consumption and physical exercise.
      CONCLUSION: The positive relationship of BMI with symptomatic GERD is also
      confirmed in the adult population of transitional Albania.

PMID- 18822940
TI  - [Quality of life in multiple sclerosis: relation to the clinical parameters of
      the disease].
AB  - PURPOSE: Multiple sclerosis is a chronic progressive disease with multiple
      neurological and psychological impairments. The object of this study was to
      investigate the relation between quality of life of MS patients and main clinical
      parameters of the disease. METHODS: The study included 100 patients diagnosed
      with multiple sclerosis who were treated at the Department of Neurology, Clinical
      Center University in Sarajevo. Quality of life was evaluated by using MSQOL-54
      questionnaire. Internal consistency of Bosnian MSQOL-54 version was evaluated.
      Associations between disability level (EDSS score), clinical type, disease
      duration, presence of pain and sphincteral problems and the MSQOL-54 physical and
      mental health composite scores were determined. RESULTS: The MSQOL -54
      questionnaire, translated to Bosnian, proved to be highly reliable (Cronbach alfa
      > 0.75 on all scales). All clinical determinants used in the sudy proved to be
      significantly related to the quality of life scores based on the Mann-Whitney
      test (p < 0.05). Method of linear regression analysis showed presence of pain and
      EDSS score as the most significant independent predictive factors of the physical
      health composite score (R2 = 0.827). The presence of pain and clinical type of
      disease, proved to be independent predictive factors of the mental health
      composite score with present, but less significant role of EDSS score (R2 =
      0.598). CONCLUSION: The presence of pain retained the most significant role in
      the prediction of both physical and mental composite scores, which proved the
      importance of pain management in treatment of MS patients. Disability level (EDSS
      score) showed minor importance in predicting mental health composite scores which
      proved deficiency of clinical scales and emphasize the importance of the quality
      of life measures as independent criteria in the evaluation of multiple sclerosis
      patients.

PMID- 18822941
TI  - [Low intensity ultrasound for more rapid healing of distal radius fractures].
AB  - Distal radius fractures are most often treated conventionally. With this paper we
      wish to show that by stimulating the distal radius fracture with the specific low
      intensity ultrasound the splicing is more rapid, complications reduced and by
      that also the healing time is shorter. The basic goal of the research is to reach
      the answer by using the adequate equipment on one group of respondents, can we
      with the programmed application of specific low intensity ultrasound in treatment
      can reach shorter joining time of the distal radius fracture compared to the
      controls. The research is conducted at the Clinic for Orthopedic Surgery and
      Traumatology of the Clinical Center in Sarajevo where we evaluated 60 patients
      with the distal radius fracture (intra and extra articulare) classified according
      to Frykman. First group of 30 patients were treated with the use of low intensity
      ultrasound and external immobilization, and the second group of 30 patients, with
      classic treatment with use of external immobilization and without use of
      ultrasound. Based on results we can conclude that the above mentioned treatment
      of distal radius fractures with use of low intensity ultrasound makes healing and
      course of treatment more rapid.

PMID- 18822942
TI  - [Outcome of the pediatric post-traumatic contracture of the elbow].
AB  - INTRODUCTION: Pediatric elbow contractures may happen as a consequence of the
      various injuries in the elbow area. PURPOSE: The aim of this article has been to
      analyze outcome of the therapy of the pediatric elbow posttraumatic contracture
      in relation to primary injury and to establish if the age of the children has
      effect on the length of hospital stay of the children with posttraumatic elbow
      contractures. WORK METHOD: We analyzed 75 children (51 boys and 24 girls);
      average age 9.1 +/- 3.2 years that have been treated in Rehabilitation center
      because of the posttraumatic elbow contractures. The average duration of
      rehabilitation was 40.1 days. Rehabilitation included procedures of the physical
      therapy and splints. The other group of the 80 healthy children was control
      group. Range of motion of elbow joint was measured for each child by goniometry.
      WORK RESULTS: The most often pediatric elbow contractures were in the children
      with supracondylar fractures (39 or 52%) at the beginning of the therapy and at
      the end of the therapy in the children with condylar fractures (7 children or
      9.3%). Outcome of the therapy was the best in the children with supracondylar
      fracture (34 children or 87.2% had full range of motion of the elbow at the
      discharge). The average value of the range of motion of the elbow joint after
      physical therapy was 124.1(0). Outcome was the best in the children with
      supracondylar fractures. Age of the children was not significantly correlated
      with length of hospital stay (Pearson's coefficient of correlation, r =
      0.267282). DISCUSSION AND CONCLUSION: Physical therapy has favorable effect on
      the outcome of the therapy of the pediatric elbow contractures and age of the
      children did not significantly correlate with length of hospital stay.

PMID- 18822943
TI  - Test for obscure bleeding vs colonoscopy in the prevention of colorectal cancer.
AB  - INTRODUCTION: Colorectal cancer is one of the most common forms of cancer and its
      frequency has been on the constant and significant increase over the past 20
      years. Prevention aiming for early precancerous detection, results in huge
      financial savings in the health care system. METHODOLOGY AND TEST SUBJECTS:
      Prospective randomized clinical research was conducted on 150 randomly chosen
      asymptomatic persons over the age of 50, with positive family history. All test
      subjects were given a Haemoccult test and colonoscopy examination. Primary
      objective of the research was to detect precancerous symptoms of colorectal
      cancer or large intestine cancer in the early stage of the disease when it is
      therapeutically curable. Secondary objective was to prove that colonoscopy
      represents an obligatory examination of the large intestine, as well as to
      introduce a Haemoccult test as a regular diagnostic procedure on the level of
      primary and secondary health care for asymptomatic patients over the age of 50.
      RESULTS: Out of 80/230 test subjects who did not fully complete the examination,
      62 (77.5%) did not respond to the test reading for obscure bleeding, whereas 18
      of them did not consent to be given a colonoscopy examination. Two registered
      neoplasm were found in the rectosigmoid colon, and the polyps were found in
      rectosigmoid colon in over 2/3 of the patients. In 125/150 test subjects, the
      test for obscure bleeding was negative (p < 0.001), but the colonoscopy procedure
      proved that 11 patients had precancerous changes (polyps). This proved that the
      test was not highly sensitive and it was recommended that it should be conducted
      in combination with colonoscopy. Patients with positive test (n = 14) had 8
      normal colonoscopy results, but the difference was not significant. CONCLUSION:
      Application of the test for detection of obscure bleeding once a year, in
      combination with flexible colonoscopy every 5 years, significantly reduces the
      risk of colorectal cancer inception.

PMID- 18822944
TI  - [Presence of depressive disorder among patients with epilepsy in relation to the
      duration of illness and type of antiepileptic therapy].
AB  - INTRODUCTION: Interictal depression as a co morbid disorder can be seen among
      more than 40% of patients with epilepsy. Epilepsy duration as well as selected
      antiepileptic drugs can be suitable for the development of depressive disorder in
      many aspects. AIM: To test relation between depressive disorder in patients with
      epilepsy, duration of illness and type of antiepileptic therapy. PATIENTS AND
      METHODS: Prospectively, by random selection, we have tested 300 patients with
      epilepsy, with or without depressive affective disorder at the Outpatient
      Department for Epilepsies in the Clinical Center of Sarajevo University. All
      patients answered Beck and Hamilton depression scales. RESULTS: This research
      involved male patients which made 54% of baseline at the average age of 37.7
      years SD = 12.86, as well as female patients at average age of 32.83 years SD =
      12.26. Depressive disorder according to the results at the Beck scale was present
      in 34%, and according to the Hamilton scale in 38.9% of patients. Carbamazepin as
      monotherapy was applied for more than a half of the baseline, Phenobarbital as
      monotherapy and combined with Carbamazepin significantly more frequently among
      men's (p < 0.0001). Duration of illnesses longer than 20 years had 56% women with
      the expressed depressive disorder, compared to the 42% men's with depression (p <
      0.01). CONCLUSION: Depressive disorder occurs significantly more frequently among
      women with the longer epilepsy duration, as well as among male patients who had
      Phenobarbital as single or add on therapy.

PMID- 18822945
TI  - [Temporoparietal pedicled flap for orbital reconstruction].
AB  - INTRODUCTION: This is excellent technique for orbital cavity reconstruction. The
      pericranial flap and flap of superficial temporoparietal fascia are supplied by
      superficial temporal artery and vein. These flaps are used as skin carrier
      without hairs of retroauricular area that can be moved to area of eye socket.
      PATIENT AND METHODS: In twenty patients the temporoparietal peduncular fascial
      flap (TPFF) for reconstruction of orbital bone defects regardless of etiology.
      The soft structures and periorbital bones were reconstructed. RESULTS: The
      reconstruction gave good esthetic and functional results in all patients that
      were followed in next six months. In six patients the bottom of eye socket is
      reconstructed and prepared for eye prosthesis. The occlusion of eye socket is
      done in ten patients after eye removal. In four patients bone defect were
      reconstructed with vascular pericranial peduncular flap of parietal bone.

PMID- 18822946
TI  - Use of lamotrigine in medically intractable epilepsies in children.
AB  - Medically intractable epilepsies are defined as seizures that are not controlled
      after an adequate trial with 2 first-line antiepileptic drugs (AED). Evidence in
      the literature show that these patients have many dysfunctions in their lifes.
      Lamotrigine is part of group of "newer antiepileptic drugs". Goal of this paper
      was to show what benefit is expected with introduction of add-on therapy with
      lamotrigine in patients with medically intractable epilepsies. Study was done in
      period 2002-2007 at Paediatric Hospital in Sarajevo. Inclusion criteria were:
      established diagnose of epilepsy, medical intractability defined as seizures not
      controlled after an adequate trial with 2 first-line antiepileptic drugs, age of
      more than 2 years and less than 18 years. Total of 61 children were assessed, 35
      male and 26 female. Average age was 61.3 months at diagnosis of epilepsy. Add-on
      therapy with lamotrigine started in average about sixteen months after the
      diagnosis, with average age at starting the therapy of 77.4 months. Predominant
      type of seizures were partial seizures (with or without secondary generalization)
      in 67.20% cases, primarily generalized tonic clonic seizures in 13.11% cases,
      typical and atypical absences in 11.48% cases and myoclonic seizures in 8.20%
      cases. Reduction in seizure frequency was very good (76-100% reduction) in 37.70%
      of patients, good (51-75%) in 21.31%, fair (26-50%) in 9.84 and poor (less than
      25%) in 31.14%. Chances of poor outcome were greater in patients with partial
      seizures. Side effects were noticed in 8.2% patients (6,56% with skin rash).
      Lamotrigine has showed good efficacy and safety profile. It is providing new
      efficient and well tolerated options for treatment for medically intractable
      epilepsies.

PMID- 18822947
TI  - [Urgent ultrasound in clinical practice].
AB  - Ultrasound (US) has been recognized as a powerful tool for use in the diagnosis
      and evaluation of many diseases in clinical practice. The possibility of
      immediate bedside US examinations in the evaluation of specific emergent
      complaints makes it an ideal tool for the emergency specialist. Correct diagnosis
      of potential life-threatening emergencies such as hematoperitoneum following
      blunt trauma, abdominal emergencies, ectopic pregnancy, pericardial tamponade,
      and aortic aneurysms with US evaluation can be easily made. Emergency physicians
      now view screening ultrasonography as highly focused and limited to answer on
      select set of questions. These questions include: Is there a pericardial effusion
      present? Are there gallstones present? Is there hydronephrosis evident? Is there
      free peritoneal fluid? Is there intrauterine pregnancy? Is there an abdominal
      aortic aneurysm (AAA) present? Is there a foreign body? It is clear that
      emergency screening ultrasound is now accepted tool for the rapid evaluation of
      the emergency patient. Using this effective diagnostic and therapeutic tool in
      emergency units our patients will have efficient, safe, and accurate health care.

PMID- 18822948
TI  - [Hypertension in pregnancy].
AB  - About 50,000 women dead due to result hypertension in pregnancy every year
      worldwide. Frequency of hypertension in pregnancy is 5-10% and complicate
      pregnancy. Control of high blood presure in pregnancy and therapy of hypertension
      are elements that prevent complication as a praeclampsia, eclampsia, abruption of
      placenta and operation end pregnancy. Aim of work is to establishing frequency of
      hypertension of controlled group of pregnen women and determinate results of
      pregnancy in pregnant women with high blood presure. The sample were 230 pregnant
      women which we controlled in Health Care Sapna. Hypertension was found at 7
      pregnant women or 3.04%, at 14.28% was found chronic hypertension and at 87.1%
      was found gestation hypertension. Pregnant women were controlled, averagely 4
      times and pregnant women with hypertension were controlled 8 times. Hypertension
      was treated with drugs at 6 pregmnant women with hypertension and one pregnant
      women did not take a medicine. 28.57% pregnant women with hypertension was
      delivered Caesarean section and 71.42% was vaginal delivery. Pregnancy of one
      pregnant women with chronic hypertension who did not take medicine was
      complicated of abruption of placenta and she was delivered Caesarean section.
      Pregnant women with gestation hypertension did not complicate during delivery.
      CONCLUSIONS: Regular control and therapy of hypertension during pregnancy can
      significantly reduce perinatal morbidity and mortality. Health educated pregnant
      women is important for control pregnancy as using advise and regular treating of
      medicine of pregnant women.

PMID- 18822949
TI  - [Brucellosis spondilitis in a ten year boy].
AB  - INTRODUCTION: Brucellosis is acute infectious disease classified as zoonosis,
      which can leave humans with chronic damages and disability. It can appear as
      sporadic cases or a smaller epidemic anywhere in the world but it is more common
      in some areas and there it presents significant public health issue. Clinical
      picture is very variegated. A long period of latency is possible, unnoticed
      asymptomatic start or forms with mild clinical picture up to the forms with per
      acute septic-toxic shock and possible lethal outcome. Symptoms of general
      infectious syndrome, wave like (undulating) temperature, profuse night sweat,
      muscle, bone and joint pain can be considered to be characteristic. Diagnosis is
      made based on epidemiological data, clinical findings, microbiological and
      serological tests. Differentially diagnostic all long-lasting febrile diseases
      may be considered and disease with neuralgic and arthralgic syndromes. Therapy
      includes antibiotics and prevention implies sanitary veterinary control, food
      control and measures of professional protection. METHODS: This paper
      descriptively describes clinical course of the disease in ten year old boy with
      brucellosis spondylitis. CASE REPORT: Ten year old boy was hospitalized for
      febrile condition and acute pain in back and abdomen of unknown etiology. We did
      diagnostic and therapeutic treatment with multidisciplinary approach and due to
      information on previous cases of brucellosis in family we also added tests to
      brucellosis. Diagnosis of brucellosis spondylitis is made based on MRI of
      lumbosacral spine and is confirmed with positive serological tests and positive
      blood cultures to Brucella melitensis. The boy had no other localized foci of the
      disease in other organs or systems. Etiological treatment was done in accordance
      to recommended antimicrobic scheme. A complete recovery was achieved with further
      need for observation of condition and Elisa titer to this agent. CONCLUSION:
      Osteoarticular form of brucellosis is relatively common focal form of the disease
      in adult patients but not so common in children. Syndrome of acute lumbosacral
      pain in children is of unknown etiology and diagnostic procedures must include
      infectious diseases with possible osteo-articular symptoms including brucellosis.

PMID- 18822950
TI  - [Case report of successful treating of refractory form of chronic lymphatic
      leukemia in Binnet C stage by using anti-CD52 antibodies].
AB  - Chronic lymphatic leukemia (CLL) is the most frequent type of leukemia in western
      world, and a choice of treatment modality depends on current stage of disease.
      Clinical condition of patient considered as Binnet C stage, requires treatment.
      Standard polyhemiotherapy (FC protocol) does not always warrant adequate and
      satisfactory response. This case report reviews the patient with CLL in Binnet C
      stage, who did not respond on FC protocol in expected way, meaning, hematological
      and medullar response was not detected. Twelve weeks therapy of monoclonal
      antiCD52 antibody (MabCampath) was than applied, resulting in normalization of
      all parameters of disease activity, which was desired effect of the therapy.
      Administration of monoclonal antiCD52 antibody is justified in case of resistance
      on conventional previously applied means of therapy.

PMID- 18822951
TI  - Traumatic rupture of the bronchus intermedius in closed chest trauma.
AB  - Traumatic rupture of the major intrathoracic airway following blunt thoracic
      trauma is a potentially lethal injury which can be repaired successfully if the
      diagnosis is made early. Early repair of the bronchus will ensure a good anatomic
      result and almost complete return of pulmonary function. This article describes
      the situation in a patient with complete transversal and partial longitudinal
      rupture of the bronchus intermedius after car accidents. Bronchus injury was
      repaired primarily with uneventful recovery.

PMID- 18822952
TI  - [Lung lymphangioleiomyomatosis (LAM)].
AB  - Lymphangioleiomyomatosis (LAM) is extreme rare diffuse lung disease of unknown
      cause seen almost exclusively in women of child-bearing age and rarely
      postmenopausal which indicates the involvement of hormones-estrogens. It results
      from proliferation of the cells having a smooth muscle cell phenotype (LAM cells)
      in the lung, and very often in the kidney and axial lymphatics and lymph nodes or
      any combination. It may occur sporadically or in association with the
      neurocutaneous syndrome--tuberous sclerosis. LAM cell proliferation may obstruct
      bronchioles, lymph vessels and venules that lead to airflow obstruction,
      formation of lung cysts, bullas and pneumothoraces, chylothorax, chylous ascites,
      hemosiderosis and hemoptysis. Approxymately 400 cases of LAM have been reported
      so far, most of them in USA. The average survival is about 8.5 years. There is no
      specific therapy. There are attempts with progesterone, lung transplantation,
      Doxycicline besides the symptomatic therapy. A new drug Rapamycin is tested. We
      are reporting 43-year old woman admitted in the Clinic for pulmonary diseases and
      TB "Podhrastovi" because of progressive dyspnea and suspect lung diffuse
      fibrosis, after the surgical treatment of spontaneous pneumothorax. The diagnosis
      of lung lymphangiomyomatosis was established by chest X ray, computerized chest
      tomography (CT), pathohistological findings of open lung biopsy. The treatment
      with progesterone is underway with other symptomatic therapy.

PMID- 18822953
TI  - Ibn al-Haitham--father of optics and describer of vision theory.
AB  - Among famous Arabic doctor belongs also Ibn Al-Haitam (known in the west as
      Alhazen) which is considered to be the greatest Muslim doctor and one of the
      greatest researches of optics for all times. Al Haitam is born in city Basra and
      immigrated to Egypt during reign of Caliph Al Hakim. He is quoted as excellent
      astronomer, mathematician and doctor as well as one of the best commentators of
      the Galen and Aristotle's work. He is the first medical scholar who teaches that
      light "does not originates from the eye but on opposite enters the eye", and in
      that manner corrects the wrong opinion of the Greeks about the nature of vision.
      According to this scholar retina is the center of vision and the impressions that
      it receives are transferred to the brain by the optical nerve, in order that
      brain afterwards create visual image in the symmetrical relationship for both
      retinas. Al-Haitam was the most important researcher of optics in Islam. He was
      convinced that the adequate theory of vision must combine Euclid and Ptolemy
      "mathematical" approach and "physical doctrine of the naturalists. The result of
      his reflections in the paper "Optics", supported by the experimental approach, is
      the new theory of vision, much richer and perfected than any before. He thought
      that light and color, two physical features that exist independently from the
      observed subject, in strait lines originates from the each point of visible
      object. Al Haitam concludes that what we perceive is actually the object which is
      on a certain distance from the eye and which have certain shape and size, and
      vision itself is the result of intervention by the visual material received by
      the brain and stored information's from previous experiences. Reception
      hypothesis (intromission) Al-Haitam exposed to mathematical testing, and then
      incorporated into already developed perception theory, which is still not
      completely explored by historians. In his experiments he used "dark chambers",
      trying to confirm the features of light, such as expansion in straight lines,
      reflexion and refraction of the light beams. Basic stand point which he supported
      was that the vision is the result of impression which light leaves on the sight
      sense, he supported it based on the experience that the eye "retains an image" or
      has pain when looking into bright light. Theory of vision by Haitam Optics,
      written in Egypt during the first half of XI century, overmatches Galen, Euclid
      and Ptolemy ones.

PMID- 18822954
TI  - [Advance in the study of compounds inducing the expression of heme oxygenase-1].
AB  - Heme oxygenase-1 (HO-1) is a cellular stress protein, and its expression plays an
      important regulatory role in a lot of physiological and pathological processes.
      Although the expression of HO-1 in most tissues of body is low, a number of
      clinical and pharmacological experiments have proved that many compounds can
      induce HO-1 expression. The increase of HO-1 expression is the result of
      regulating different signaling pathways and transcription factors, and this
      induction of HO-1 is suggested to be partially therapeutic efficacy of these
      compounds. This article summarizes some kinds of compounds in this field of
      research at home and abroad over the last 10 years, and provides a brief analysis
      of the mechanism.

PMID- 18822955
TI  - [Advances in the MDCK-MDR1 cell model and its applications to screen drug
      permeability].
AB  - This article introduces the characteristics and establishment of MDCK-MDR1 cell
      line, and its applications as an in vitro model for the assessment of the
      membrane permeability properties of drugs. MDCK-MDR1 cell model is widely used in
      drug screenings, and the study of mechanisms of drug interaction and absorption
      or transport. The review summarizes the progress and applications of MDCK-MDR1
      cell model. Because there is high polarized P-glycoprotein (P-gp) expression in
      MDCK-MDR1 cells, it could be used as a drug transport model to screen P-gp
      substrates or inhibitors, as well as models of intestinal mucosa, blood brain
      barrier and kidney. Although there are some disadvantages in MDCK-MDR1 cell
      model, it is an effective tool for implementing permeability of drug in an
      optimal fashion.

PMID- 18822956
TI  - [Recent progress in the study on antitumor drugs targeting hypoxia-inducible
      factor-1].
AB  - Hypoxia-inducible factor-1 (HIF-1), as a transcription factor, plays an important
      role in the adaptation to hypoxic microenvironment within tumors. It can induce a
      series of genes transcription that participate in angiogenesis, glucose
      metabolism, cell proliferation, and cell migration/invasion. Thus HIF-1 not only
      allows cancer cells to survive in hypoxic microenvironment, but also makes the
      tumor more aggressive. Moreover, HIF-1 also induces tumors to acquire resistance
      to chemo-/radio-therapy, and is related to poor prognosis. HIF-1 emerges
      gradually as a potential target to develop new antitumor drugs. This paper
      reviews recent progress in this field.

PMID- 18822957
TI  - [Inhibitory action of hydroxysafflor yellow A on inflammatory signal transduction
      pathway related factors in rats with cerebral cortex ischemia].
AB  - Hydroxysafflor yellow A (HSYA) is a main active monomer purified from Carthamus
      tinctorius L. The research is to study the inhibitory effect of HSYA on the
      inflammatory signal transduction pathway related factors which were induced by
      permanent cerebral ischemia in rats. By using the successive administration at a
      30 min interval of HSYA and the rats permanent focal cerebral ischemia model
      established by a intraluminal suture occlusion method. After cerebral artery
      occlusion 3, 6, 12 and 24 h, cortex was removed for the next experiments. Western
      blotting was used to detect the expression of p65 protein and the phospho-IkappaB
      alpha (pIkappaB-alpha) in the cytoplasm and nucleus. Nuclear factor-kappaB (NF
      kappaB) DNA binding activity was measured by Trans-AM transcription factor assay
      kits. mRNA expression of cytokines TNF-alpha, IL-1beta, IL-6 and IL-10 was
      measured by the RT-PCR method. The result showed that intravenous injection of
      HSYA (10 mg x kg(-1)) to rats after cerebral occlusion, the p65 translocation
      activity and the phosphorylation of IkappaB-alpha were significantly inhibited.
      At the same time, HSYA suppressed p65 binding activity and the transcriptional
      level of pro-inflammatory cytokines including TNF-alpha, IL-1beta and IL-6, and
      promoted the mRNA expression of anti-inflammatory cytokine IL-10. In conclusion,
      the anti-cerebral ischemic mechanism of HSYA may be due to its inhibition of NF
      kappaB activity and the mRNA expression of cytokines in the inflammatory
      transduction pathway.

PMID- 18822958
TI  - [Dihydroartemisinin down-regulates the expression of transferrin receptor in
      myeloid leukemia cells].
AB  - This article reports the effect of dihydroartemisinin (DHA) on transferrin
      receptor (TfR) in myeloid leukemia cells by establishing the model of normal iron
      HL60 and K562 cells and iron overload K562 cells in vitro. The TfR content of
      myeloid leukemia cells was determined by flow cytometry, and the effect of DHA on
      iron content in K562 cells was determined by atomic absorption spectrophotometric
      analysis. Furthermore, the inhibitory effect of DHA on the anti-proliferation and
      expression of TfR protein and mRNA in myeloid leukemia cells was studied. As a
      result, DHA effectively decreased the TfR content and down-regulated TfR protein
      expression in normal iron HL60 and K562 cells in a dose- and time-dependent
      manner and inhibited the cell proliferation. The IC50 were 1.74 and 11.33
      micromol x L(-1), respectively. DHA exerted more pronounced inhibitory action on
      expression of TfR protein and mRNA in iron overload K562 cells. Compared to
      normal iron K562 cells, the TfR protein and mRNA levels were lowered by 28.1% (P
      < 0.01) and 26. 2% (P < 0. 05) , respectively, after DHA treatment for 48 h in
      iron overload K562 cells. Moreover, DHA decreased the iron content of iron
      overload K562 cells and inhibited the proliferation of iron overload K562 cells
      more potently. DHA effectively down-regulated the TfR content as well as
      expression of TfR protein and mRNA in normal iron myeloid leukemia cells. DHA
      also inhibited the proliferation of HL60 and K562 cells. The anti-proliferation
      effect of DHA on iron overload K562 cells was more striking.

PMID- 18822959
TI  - [Methyl jasmonate induces apoptosis of human neuroblastoma cell line BE(2) -C and
      its mechanism].
AB  - This study is to explore the inhibitory effect of methyl jasmonate on cell
      proliferation and expression of XIAP and survivin of human neuroblastoma cell
      line BE(2)-C. After cultivation of 1 - 2 mmol x L(-1) jasmonates with BE (2) -C
      cells for 6 - 24 h, the growth inhibiting rates of BE (2) -C cells were studied
      by MTT colorimetry. Cell proliferation was detected by colony formation assay.
      Cell cycle phases were assayed by propidium iodide staining flow cytometery. Cell
      apoptosis was inspected by acridine orange-ethidium bromide fluorescent staining,
      Hoechst 33258 fluorescent staining, and Annexin V-FITC and propidium iodide
      staining flow cytometry. Expressions of cyclin D1, XIAP and survivin were
      determined by RT-PCR and real-time RT-PCR. Methyl jasmonate inhibited the growth
      of BE(2)-C cells in a dose- and time-dependent manner. After addition of 1, 1.5
      and 2 mmol x L(-1) of methyl jasmonate for 24 h, the inhibiting rates of cell
      growth reached 20.6% - 85.5% (P < 0.01), and the IC50 was 1.35 mmol x L(-1). The
      cell cycles were arrested at S phase. A part of cells presented the
      characteristic morphological changes of apoptosis. The early apoptotic rates were
      13.51%, 17.32%, 24.59% (P < 0.01) and the cell death rates were 29.36% , 54.73% ,
      75.52% (P < 0.01), respectively. The expression of XIAP and survivin mRNA were
      downregulated by 18.5% - 68.9% , 22.4% - 48.7% (P < 0.05), respectively, without
      change in that of cyclin D1. The results indicated that methyl jasmonate could
      significantly inhibit the growth of BE(2) -C cells through inducing cell cycle
      arrest and apoptosis, downregulating the expression of XIAP and survivin might be
      one of its molecular mechanisms of action.

PMID- 18822960
TI  - [Effects of taurine on proliferation of rat cardiac fibroblast].
AB  - This project aimed to investigate the effect of taurine on nitric oxide (NO) and
      protein kinase C alpha (p-PKCalpha) in the proliferation of cultured neonatal rat
      cardiac fibroblast (CFb) induced by angiotensin II (Ang II), and to explore the
      effect of taurine on the signal transduction pathway in CFb proliferation. The
      cultured neonatal rats CFb were isolated by trypsin digestion method. The
      proliferation of CFb was induced by Ang II and detected by thiazole blue (MTT)
      colorimetric assay. The levels of collagen I and collagen III were measured by
      the ELISA. Cell cycle was analyzed by flow cytometry. The change of NO content
      was measured by nitric acid reductase method and the protein express of p
      PKCalpha in cells was determined by Western blotting technology. Among the
      concentration of 40 - 160 mmol x L(-1), taurine could not only prevent the
      synthesis of collagen and the proliferation of CFb stimulated by angiotensin II,
      but also block CFb in the G0/G1 phase from entering the S phase, resulting in
      more cells in the G0/G1 phase and fewer in the S phase (P < 0.05, P < 0.01).
      Taurine significantly increased NO level and inhibited p-PKCalpha expression in
      CFb (P < 0.05, P < 0.01). The inhibitory effects of taurine on CFb proliferation
      and collagen synthesis might be due to inhibition of p-PKCalpha expression and NO
      content increase.

PMID- 18822961
TI  - [Effect of bicyclol on gene expression profiles in mice with liver injury induced
      by concanavalin A].
AB  - The aim of this study was to investigate the effect of the novel antihepatitis
      drug bicyclol on the gene expression profiles in concanavalin A (Con A)
      intoxicated mice by using cDNA microarray analysis. Bicyclol (250 mg x kg(-1))
      was given orally to mice three doses before Con A intravenous injection (26.5 mg
      x kg(-1)). Serum levels of aminotransferases were examined by biochemical
      methods. Liver mRNA was extracted and reversely transcribed to cDNA with the
      incorporation of labeled Cy3-dUTP and Cy5-dUTP, separately. The probes were
      hybridized to the cDNA microarray. The acquired image was scanned and analyzed by
      Cenepix Pro 3.0 software. Microarray analysis showed that 287 genes exhibited
      differential expression in bicyclol group, in which 121 genes were up-regulated
      and 166 genes were down-regulated comparing with that of untreated Con A
      intoxicated mice. The differential gene expression after bicyclol treatment was
      involved in the biotransformation, protein synthesis, degradation and circadian
      rhythm, proliferation and signal transduction. Bicyclol might regulate a series
      of genes expressions in Con A intoxicated mice.

PMID- 18822962
TI  - [Lidamycin induces apoptosis of human gastric carcinoma BGC823 cells and inhibits
      xenograft growth in nude mice].
AB  - To investigate the effect of lidamycin (LDM) on human gastric carcinoma BGC823
      cells and xenograft growth in nude mice, MTT (methyl thiazolyl tetrazolium) assay
      was used to determine the inhibition of BGC823 cell proliferation by LDM.
      Induction of apoptosis was studied by flow cytometry and TUNEL assay. The
      expression of VEGF was detected by Western blotting analysis. Athymic nude mice
      were used to determine in vivo antitumor activity. Proliferation inhibition and
      apoptosis induction were studied in lidamycin-treated cells. The expression of
      VEGF in BGC823 cells decreased in a dose-dependent manner. LDM at 0.02 mg x kg(
      1) and 0.04 mg x kg(-1) suppressed the growth of BGC823 xenografts in nude mice
      by 57% and 72%, respectively. LDM potently induces apoptosis in human gastric
      carcinoma BGC823 cells and inhibits xenograft growth.

PMID- 18822963
TI  - [Design and synthesis of a type of benzopyran derivatives with insulin
      sensitizing activity].
AB  - Ten novel compounds were designed and synthesized on the basis of compound 1,
      their insulin-sensitizing activities were evaluated in 3T3-L1 cells. Results
      showed that compound 10 exhibited strong differentiation-stimulating activity on
      3T3-L1 cells model, which indicated that compound 10 may possess well insulin
      sensitizing activity.

PMID- 18822964
TI  - [Synthesis and central none-opioid analgesic activity of SIPI5047].
AB  - Compound SIPI5047 was synthesize by using piperazine as starting material in five
      reaction steps, and its central none-opioid analgesic activity was studied. Its
      analgesic activity, pharmacological mechanism, action type and drug dependence
      were well studied in vivo and in vitro. The results show that SIPI5047 has potent
      analgesic activities in vivo, which is quite similar to morphine and also much
      more powerful than paracetamol. SIPI5047 has no efficacy to reduce fever or
      inflammation, but has an obvious action on central nervous system. SIPI5057 has
      no apparent affinity with the mu-receptor and it is an antagonist that acts on
      the polyamine site of the NMDA receptor. SIPI5057 appears no drug dependence.
      SIPI5047 is a novel central none-opioid analgesic agent and more worthy of
      further research as a new drug candidate.

PMID- 18822965
TI  - [Synthesis and 5-HT reuptake inhibition activity of biarylbenzamidine
      derivatives].
AB  - A series of biarylbenzamidine analogs were synthesized and tested for their
      biological activities of inhibiting the reuptake of 5-HT. All of them were new
      compounds, and their structures were confirmed by 1H NMR and HRMS. Preliminary in
      vitro pharmacological tests showed that all target compounds exhibited 5-HT
      reuptake inhibition activity. Among the tested compounds, 5i, 4a and 5m exhibited
      potent inhibitory activity against 5-HT reuptake in vitro. It is a chance to find
      a better precursor of SSRIs (selective serotonin reuptake inhibitors) for further
      optimization of compounds.

PMID- 18822966
TI  - A new compound from Senecio cannabifolius var integrilifolius.
AB  - Senecio cannabifolius var integrilifolius (Compositae), locally known as
      "Fanhuncao" in China, is a folk herb used for the treatment of pneumonia, virus
      influenza and bronchitis. To investigate the chemical constituents of this herb,
      water extract of the aerial parts was subjected to various chromatography on
      normal/reversed phase silica gel and Sephadex LH-20 column. Eleven compounds were
      obtained and identified on the basis of their physicochemical properties and
      spectroscopic analysis as senecine (1), p-hydroxy-benzeneacetic acid (2),
      protocatechuic acid (3), 2,5-dihydroxy-benzeneacetic acid (4), 3,4-dihydroxy
      benzeneacetic acid (5), vanillic acid (6), caffic acid (7), succinic acid (8), 2
      furoic acid (9), 1, 2, 4, 5-tetrahydro-jacaranone (10), and 4-(pyrrolidin-2-one)
      phenylacetic acid (11). Compound 1 was structurally identified to be a new
      compound; the other compounds were isolated from this plant for the first time.

PMID- 18822967
TI  - [Lignans from different processed products of Schisandra chinensis fruits].
AB  - To study the lignan components of different processed products of Schisandra
      chinensis fruits, the study was conducted with electrospray ionization mass
      spectrometry (ESI-MS) and high performance liquid chromatography (HPLC). There
      was no new lignan components detected from the products obtained with different
      processed methods, the difference was in the content of lignan components. The
      method is accurate and effective, which can be used to evaluate the quality of
      different processed products of Schisandra chinensis fruits.

PMID- 18822968
TI  - [Analysis of primary metabolites of alpha-tocopherol in human urine by liquid
      chromatography-mass spectrometry].
AB  - To investigate primary metabolites of alpha-tocopherol in human urine, the urine
      samples of five healthy volunteers after oral administration of 250 mg vitamin E
      once a day for seven days were collected within 0 -6 h in the seventh day. The
      samples were purified through C18 solid-phase extraction cartridge and analyzed
      by liquid chromatography-tandem mass spectrometry. alpha-Tocopheronic acid,
      2,5,7, 8-tetramethyl-2-(2'-carboxyethyl) -6-suphate-chroman (alpha-CEHC
      sulphate), gamma-tocopheronolactone, and 2, 5, 7, 8-tetramethyl-2-(4', 8', 12'
      trimethyl-12'-carboxy dodecanyl) -6-suphate-chroman were found in urine of
      volunteers as four primary metabolites of alpha-tocopherol. The method has shown
      to be promising for alpha-tocopherol detection with many desirable properties
      including high sensitivity and selectivity, thus providing a reliable pathway for
      further study in metabolism of alpha-tocopherol.

PMID- 18822969
TI  - [Preparation, characterization of paclitaxel-loaded Pluronic P105 polymeric
      micelles and in vitro reversal of multidrug resistant tumor].
AB  - Drug delivery system (DDS) is a novel approach to overcome multidrug resistance
      (MDR) in tumors nowadays. This work was designed to investigate a new micellar
      delivery system for in vitro reversal of resistant ovarian tumor cells, based on
      a nonionic triblock copolymer Pluronic P105 and paclitaxel (PTX). The PTX-loaded
      polymeric micelles (P105/PTX) were prepared by thin film-hydration methods. Based
      on the results of single factor experiments, the P105/PTX micelle formulation was
      optimized by employing the central composite design-response surface methodology.
      The physico-chemical properties of the P105/PTX micelles were characterized,
      including micelle size, drug loading coefficient, in vitro release behavior, etc.
      The cytotoxicity of the P105/PTX micelles was assessed against human ovarian
      tumor cell line, SKOV-3/PTX, by a standard 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyl (MTT) assay. In order to understand the possible mechanism of Pluronic
      effects in resistant tumor cells, cellular uptake study of micellar PTX or
      Rhodamine-123 (R-123) was also carried out. The results showed that the micelle
      size was about 24 nm with drug loading coefficient of 1.1% and PTX concentration
      of 700 microg x mL(-1). The cumulative release amount of PTX from the P105/PTX
      micelles was only 45.4% in 6 h (P < 0.05) and 79.6% in 24 h, whereas Taxol
      injection in 6 h released 95.2% PTX. The IC50 values of the P105/PTX micelles and
      Taxol injection against SKOV-3/PTX were 1.14 and 5.11 microg x mL(-1), and
      resistance reversion index (RRI) was 9.65 and 2.15, respectively. The micellar
      PTX or R-123 exhibited a significant increase in cellular uptake in resistant
      SKOV-3/PTX cells compared with free PTX or R-123. These results indicated that
      PTX could effectively be solubilized by Pluronic P105 block copolymers via thin
      film-hydration process and formulation optimization, producing nano-scale
      polymeric micelles with sustained release property in vitro. The P105/PTX
      micelles were effectively able to reverse resistance to PTX in SKOV-3/PTX tumor
      cells compared with Taxol injection or free PTX solution, and the enhanced
      cytotoxicity in the resistant SKOV-3/PTX cell was related to the improved
      cellular uptake of PTX by Pluronic P105 copolymers.

PMID- 18822970
TI  - [Novel method for the evaluation of the synchronicity of the chemomic
      release/dissolution of multi-component traditional Chinese medicines].
AB  - Due to the diversity of components within the traditional Chinese medicines
      (TCMs), the release profiles of the components in the TCM dosage forms vary
      dramatically and no quantification method is available to determine the variance
      yet. Based upon the principles of Kalman filter method, the authors defined a new
      parameter, relative chemomic error (epsilon), to evaluate the asynchronous nature
      of the components in TCMs, and a derivative parameter as synchronization factor
      (SF) to quantify the synchronicity of the chemome of the TCMs. The average
      synchronization factor (SF(av)) was accordingly derived to simultaneously
      quantify the release/dissolution profiles of the multi-components in TCMs.
      Randomly generated simulation data were processed to demonstrate the chemomic
      data processing and the methodology. The results indicated that the novel
      parameter epsilon was well correlated (r = 0.996 8) with the coefficient of
      variation from the conventional release profiles of all the components. As the
      asynchronicity was the intrinsic characteristics of the multi-component TCMs, the
      synchronicity might be a new target of quality control of TCMs. The methods
      established by this report can be used a quantitative tool for the evaluation of
      the chemomic release synchronization of TCMs.

PMID- 18822971
TI  - [Preparation of verapamil hydrochloride core-in-cup tablets with double-pulsatile
      and multi-phasic release].
AB  - To prepare verapamil hydrochloride (VH) core-in-cup tablets with tri-layered
      tablet and four-layered tablet as core tablets, separately, which can provide
      biphasic release with double-pulsatile and multi-phasic release, core tablets
      were prepared by direct compression method, and core-in-cup tablets by dry
      compression coated technology. The parameter, time-lag (T(lag)), was used to
      evaluate the influence of factors, such as the weight of the top cover layer, the
      amount of hydroxypropylmethylcellulose (HPMC), and the compression load on VH
      release. With the increase of the weight and HPMC amount of the top cover layer,
      the first lag time T(lag1) was prolonged. The second lag time T(lag2) of core-in
      cup tablet with four-layered tablet as core tablet increased with the increasing
      amount of HPMC K100M. With the increase of compression load among the range (6 -
      10 kg x cm(-2)), the two lag times were prolonged. Core-in-cup tablets with
      double-pulsatile and multi-phasic release released VH after the first lag time (4
      -5 h), then kept sustained release for 12 h or 13 h, finally released rapidly.
      The drug in the core-in-cup tablet only released from the top cover layer. T(lag)
      is determined by the erosion rate of the inhibitor layers (the top cover layer
      and the sustained-release layer of the multi-layer core tablet).

PMID- 18822972
TI  - [Analysis of expressed sequence tags (EST) from Panax quinquefolium root].
AB  - To investigate the profile of gene expression in American ginseng (Panax
      quinquefolium L.) and discover its functional genes, for the first time,
      expressed sequence tags (EST) library of four-year-old American ginseng roots has
      been established. According to BLAST and Gene Ontology analysis, eleven genes,
      encoding cytochrome P450, glucosyltransferase, farnesyltransferase and cyclase
      family protein, are found to be associated with ginsenosides biosynthesis. Six
      other genes are obtained encoding auxin-regulated protein, auxin response factor
      4 and auxin-repressed protein in the roots of American ginseng. In addition,
      thirteen expressed transcripts are stress-connected proteins and twelve expressed
      other transcripts are closely related to plant defense in four-year-old American
      ginseng roots. Furthermore, 62 genes no hit in BLAST and in Interproscan may be
      new genes. These results indicate EST is an useful tool for research on
      functional genomics of P. quinquefolium and it can be applied to the molecular
      modification of the ginsenosides biosynthetic pathway ultimately for improving
      the quality of American ginseng germplasm.

PMID- 18822973
TI  - [In vitro metabolic interconversion between baicalin and baicalein in the liver,
      kidney, intestine and bladder of rat].
AB  - The present study is aimed to investigate the in vitro metabolic interconversion
      between baicalin (BG) and baicalein (B) in rat liver, kidney, intestine and
      bladder. BG and B were separately incubated with rat hepatic, renal, and
      intestinal microsomes, as well as bladder homogenates, for 30 min. The
      metabolites were identified and quantified by HPLC and metabolic kinetic
      parameters were obtained by fitting the data to the Michaelis-Menten equation. In
      hepatic microsomes, renal microsomes and bladder homogenates, but not in
      intestinal microsomes, BG was transformed into B, the hydrolysis metabolite of
      BG, with K(m) values being (44.65 +/- 6.01), (92.73 +/- 11.41), (74.60 +/- 3.68)
      micromol x L(-1), respectively, and V(max) values being (12.32 +/- 0.56), (3.30
      +/- 0.18), (5.93 +/- 0.12) micromol x min(-1) x g(-1) (protein), respectively. In
      incubations with hepatic, renal, and intestinal microsomes and bladder
      homogenates, B was also transformed into BG, the glucuronidation metabolite of B,
      with K(m) values being (67.46 +/- 10.49), (226.7 +/- 71.59), (177.3 +/- 35.85),
      and (18.33 +/- 2.53) micromol x L(-1), respectively, and V(max) values being
      (14.74 +/- 0.97), (5.91 +/- 1.03), (38.14 +/- 3.60), and (1.22 +/- 0.05) micromol
      x min(-1) x g(-1) (protein), respectively. The results showed that the activity
      of UDP-glucuronosyltranferase (UGT) in intestinal microsomes was the highest
      among the four organs, and the activities of UGT were higher than that of
      glucuronidase (GUS) in hepatic, renal and intestinal microsomes, but the activity
      of GUS was higher than that of UGT in bladder homogenates.

PMID- 18822974
TI  - [Randomized controlled study on effects of the needling method for regulating
      spleen-stomach on coronary heart disease complicated by type 2 diabetes mellitus
      complicated].
AB  - OBJECTIVE: To probe into the clinical therapeutic effect of acupuncture on
      coronary heart disease complicated by type 2 diabetes mellitus (CDM) and the
      mechanism. METHODS: Using multi-central, randomized, controlled and blind
      methods, 120 cases of CDM were divided into an observation group and a control
      group, 60 cases in each group. They were treated by routine therapy for diabetes
      mellitus, and in the observation group, acupuncture at Quchi (LI 11), Hegu (LI
      4), Xuehai (SP 10), Zusanli (ST 36), Yinlingquan (SP 9), Fenglong (ST 40). Diji
      (SP 8), Sanyinjiao (SP 6), etc. were added with the needling method for
      regulating spleen-stomach; while in the control group, acupuncture was given at
      Weiwanxiashu (EX-B 3), Feishu (BL 13), Pishu (BL 20), Shenshu (BL 23),
      Yanglingquan (GB 34), etc. The treatment was given twice a day in the two groups.
      Clinical therapeutic effects were assessed according to clinical symptoms and
      signs, frequency and lasting time of angina pectoris, quantity of taking Glycerol
      Trinitrate, blood sugar, blood lipids, urinary albumin excretion rate, urinary
      beta2-microglobulin, urinary monocyte chemotactic protein-1 (MCP-1), ECG, heart
      color Doppler, etc. RESULTS: The needling method for regulating spleen-stomach
      not only could improve the symptoms and signs of the patient, but also could
      improve the degree of ST segment moving down and the function of left artrium
      relaxation, and had benign regulative effect on glycometabolism, lipids
      metabolism and urinary albumin level, with significant differences as compared
      with the control group (P < 0.05 or P < 0.01). The markedly effective rate for
      improvement of ECG was 50.00% in the observation group and 13.79% in the control
      group. CONCLUSION: The needling method for regulating spleen-stomach can improve
      the damage of heart and blood vessels induced by abnormal sugar and lipids,
      decrease the level of urinary protein, inhibit MCP-1 excessive expression,
      relieve myocardial load and raise cardiac output in the patient of coronary heart
      disease complicated by type 2 diabetes mellitus.

PMID- 18822975
TI  - [Acupoint electrogymnastics therapy for treatment of apoplectic hemiplegia: a
      multicenter randomized control study].
AB  - OBJECTIVE: To observe the therapeutic effect of acupoint electrogymnastics
      therapy on apoplectic hemiplegia, so as to further popularize this therapy in
      treatment of apoplectic hemiplegia. METHODS: Using three-central, randomized,
      controlled, multi-blind methods, 153 cases were divided into an electrogymnastics
      group (n = 77) and an electroacupuncture group (n = 76). They were treated with
      acupoint electrogymnastics (AE) and traditional electroacupuncture (TEA),
      respectively. Shousanli (LI 10) and Waiguan (TE 5) on upper limbs and
      Yanglingquan (GB 34) and Zusanli (ST 36) on the lower limbs were selected in the
      two groups. A JD-2008 hemiplegia treatment apparatus was used in the AE group.
      Fugl-Meyer method was used for assessment of motor function and sense function of
      the four limbs, balance function and joint activity, etc. before and after
      treatment. RESULTS: In the motor function and sense function of four limbs,
      balance function and joint activity in the two groups had significant improvement
      after treatment (both P < 0. 001) with no significant difference between the two
      groups (P > 0.05). CONCLUSION: Both acupoint electrogymnastics (AE) and
      traditional electroacupuncture (TEA) have a similar therapeutic effect on
      apoplectic hemiplegia, but AE has the advantages of safety, reliability and
      convenience in operation, so it is suitable for long-term rehabilitation
      treatment of the patient and for popularization in hospital of basic level.

PMID- 18822976
TI  - [Effects of acupuncture at Neiguan (PC 6) on function of sinoatrial node].
AB  - OBJECTIVE: To observe effects of acupuncture at Neiguan (PC 6) on function of
      sinoatrial node, so as to provide experimental basis for clinical application of
      Neiguan (PC 6) to treatment of heart diseases. METHODS: Fifty cases of heart
      diseases were randomly divided into 2 groups, a no-blocking group (n = 35) and a
      blocking group (n = 15). In the no-blocking group, sinoatrial node recovery time
      (SNRT), sinoatrial conduction time (SACT), sinoatrial node effective refractory
      period (SNERP) and heart rate (HR) were determined by using esophagus-left
      cardiac atrium regulating pulsation technique before and after acupuncture at
      Neiguan (PC 6); and in the blocking group, the vegetative nerve was blocked by
      intravenous injection of Propanolol and Atropine, and then SNRT, SACT, SNERP and
      intrinsic heart rate (IHR) were detected before and after acupuncture. RESULTS:
      In the no-blocking group there were significant differences in SACT, SNERP and HR
      (all P < 0.05) and no significant difference in SNRT (P > 0.05) before and after
      treatment. In the blocking group, there were no significant differences in SNRT,
      SACT and SNERP and a significant difference in IHR before and after acupuncture
      (P < 0.05). CONCLUSION: Acupuncture at Neiguan (PC 6) has a significant effect on
      function of sinoatrial node, and the mechanism is possibly related with the
      bidirectional regulative action of acupuncture at Neiguan (PC 6) on the autonomic
      nerve in the sinoatrial node.

PMID- 18822977
TI  - [Clinical observation on injection of small dose of morphine into Neiguan (PC 6)
      for treatment of chest pain in the patient with acute myocardial infarction].
AB  - OBJECTIVE: To probe into an effective injection way of Morphine for treatment of
      chest pain of acute cardiac infarction. METHODS: Ninety cases of myocardial
      infarction were randomly divided into 3 groups, an acupoint-injection group, an
      intravenous injection group and a hypodermic injection group, 30 cases in each
      group. The acupoint-injection group were treated with injection of 2 mg Morphine
      into bilateral Neiguan (PC 6) respectively, and the intravenous injection group
      with intravenous injection of 5 mg Morphine and the hypodermic injection group
      with hypodermic injection of 5 mg Morphine, and other treatments were same in the
      3 groups. The analgesic effects were assessed with visual analogue scale (VAS) 5,
      10, 30, 60 and 180 minutes after treatment and the complications were observed.
      RESULTS: There were no significant differences among the 3 groups before
      treatment in the VAS score (P > 0.05). The analgesic effect in the acupoint
      injection group was better than those in other two groups 5 min, 30 min and 180
      min after treatment (all P < 0.01). The incidence rate of nausea and vomiting of
      0.3% in the acupoint-injection group was significantly lower than 40.0% in the
      intravenous injection group and 20.0% in the hy podermic injection group (all P <
      0.01). CONCLUSION: Injection of small dose of Morphine into Neiguan (PC 6) has a
      definite therapeutic effect on chest pain of acute myocardial infarction with
      earlier analgesic effect, smaller dose of Morphine, longer analgesic duration and
      less complications.

PMID- 18822978
TI  - [Observation on therapeutic effect of acupuncture combined with medicine on
      Parkinson disease].
AB  - OBJECTIVE: To observe therapeutic effect of acupuncture on Parkinson disease
      (PD). METHODS: Sixty cases of PD were randomly divided into 2 groups, an
      acupuncture plus medication group and a medication group, 30 cases in each group.
      The acupuncture plus medication group were treated with acupuncture at Shenting
      (GV 24), Baihui (GV 20), Sishencong (EX-HN 1), etc. and oral administration of
      Madopa, and the medication group only with Madopa. Their therapeutic effect and
      scores of Parkinson disease function rating scale (modified UPDRS) were compared.
      RESULTS: The total improvement rate of 80.0% in the acupuncture plus medication
      group was significantly higher than 60.0% in the medication group (P < 0.05); the
      decrease of cumulative score of UPDRS in the acupuncture plus medication group
      was better than that in the medication group (P < 0.05). CONCLUSION: Acupuncture
      has a certain therapeutic effect on PD.

PMID- 18822979
TI  - [Effects of the needling method for regulating kidney and smoothing liver on
      endocrine and immune functions in the patient with hyperplasia of mammary
      glands].
AB  - OBJECTIVE: To probe into a better acupoint association for treatment of
      hyperplasia of mammary glands and the mechanism. METHODS: Two hundred cases were
      randomly divided into a regulating kidney and smoothing liver needling group, a
      routine acupuncture group and a Chinese medicine group. The regulating kidney and
      smoot hing liver needling group were treated with acupuncture at Shenshu (BL 23),
      Mingmen (GV 4), Fengfu (GV 16), Lingxu (KI 24), Shenfeng (KI 23), Bulang (KI 22),
      Qimen (LR 14), etc. and the routine acupuncture group with acupuncture at Zusanli
      (ST 36), Tanzhong (CV 17), Ganshu (BL 18), Rugen (ST 18), Neiguan (PC 6), Qimen
      (LR 14), once daily; and the Chinese medicine group with oral administration of
      Rupixiao tablet, 6 tablets each time, thrice each day. After they were treated
      for 2 menstrual cycles, the therapeutic effects and changes of E2, PRL, P, CD3+,
      CD4+ and CD8+ were observed. RESULTS: The clinical therapeutic effect and the
      total effective rate for TCM syndromes were 92.0% and 94.0% in the regulating
      kidney and smoothing liver needling group, 86.0% and 88.0% in the routine
      acupuncture group and 78.0% and 84.0% in the Chinese medicine group, with a
      significant difference among the 3 groups, the former being better than the other
      two groups; after treatment, serum PRL, P, P/E2 significantly improved in all the
      3 groups (P < 0.05) and the regulating kidney and smoothing liver needling group
      was better than other two groups in decreasing PRL and increasing P, P/E2 (P <
      0.05); and E2, CD8+, CD4+/CD8+ significantly improved in the regulating kidney
      and smoothing liver needling group and the routine acupuncture group, the former
      being better than the later in decreasing E2 (P < 0.05). CONCLUSION: The
      regulating kidney and smoothing liver needling method is an effective method for
      treatment of hyperplasia of mammary glands and it has regulative action on
      endocrine and immune functions in the patient with hyperplasia of mammary glands.

PMID- 18822980
TI  - [Effects of electroacupuncture on urinary bladder function after radical
      hysterectomy].
AB  - OBJECTIVE: To observe the effect of electroacupuncture on recovery of urinary
      bladder function after radical hysterectomy. METHODS: One hundred and ten cases
      were randomly divided into an electroacupuncture (EA) group and a control group,
      55 cases in each group. In the control group, the urinary tube was placed and
      kept with routine method and the urinary bladder was rinsed, and from the eighth
      day the abdomen was radiated with TDP, 30 min each day, for 5 days. In the EA
      group, on the basis of treatment in the control group EA was given at Sanyinjiao
      (SP 6), Zusanli (ST 36), Waiguan (TE 5), Shuidao (ST 28), Guilai (ST 29), etc.
      from the eighth day to twelfth day after operation. The recovery time of urinary
      bladder function after radical hysterectomy, urine dynamic indexes and
      hospitalization days were compared between the two groups. RESULTS: The cases of
      the bladder function recovery, retention of urine, urinary incontinence were
      51(51/55), 4(4/55), 0 on the 14 th day after operation and 53(53/55), 2(2/55), 0
      on the 28 th day in the EA group, and 27(27/55), 25(25/55), 3(3/55) on the 14 th
      day and 43(43/55), 11(11/55), 1(1/55) on the 28th day in the control group,
      respectively, with a very significant difference between the two groups (P <
      0.01); the EA group in residual urine volume, bladder volume, mean urinary
      flowing rate was better than the control group on the 14 th day after operation
      (P < 0.01 or P < 0.05); the hospitalization days after operation was (21.1 +/-
      3.3) days in the EA group and (25.5 +/- 3.5) days in the control group, the
      former being shorter than the later (P < 0.01). CONCLUSION: EA can promote
      recovery of bladder function, shorten the keeping time of urinary tube after
      radical hysterectomy, which is benefit to decreasing incidence rate of urinary
      system infection and shortening hospitalization days.

PMID- 18822981
TI  - [Observation on therapeutic effect of catgut implantation at acupoints on
      exercise fatigue and study on the mechanism].
AB  - OBJECTIVE: To probe into the therapeutic effect of catgut implantation at
      acupoint on exercise fatigue and to study on the mechanism. METHODS: Catgut
      implantation was given at main points Guanyuan (CV 4), Shen shu (BL 23), Mingmen
      (GV 4), Zusanli (ST 36), Sanyinjiao (SP 6) in 41 players during training for 2
      courses. Training-related condition and changes of blood testosterone (T) and
      hemoglobin (Hb) before and after training were observed. RESULTS: After
      treatment, sleeping quality, the mental state at the time of getting out of bed
      in the morning, appetite, training wish, training stamina, training quality,
      training attention, etc. in the player significantly improved, and blood T and Hb
      levels significantly increased. CONCLUSION: Catgut implantation at acupoints can
      significantly improve exercise fatigue in the player and the mechanism is
      possibly related with increase of testosterone and hemoglobin levels.

PMID- 18822982
TI  - [Observation on therapeutic effect of electroacupuncture combined with local
      blocking therapy on acute gouty arthritis].
AB  - OBJECTIVE: To search for a new method for treatment of acute gouty arthritis.
      METHODS: One hundred cases of acute gouty arthritis were randomly divided into an
      observation group and a control group. The observation group were treated with
      local blocking and electroacupuncture at Yinbai (SP 1), Taichong (LR 3),
      Sanyinjiao (SP 6), Zusanli (ST 36), Fenglong (ST 40), Yinlingquan (SP 9) and Ashi
      points, and the control group were treated with oral administration of 25 mg
      Indomethacin, thrice each day, and 100 mg Allopurinol, thrice daily. The
      therapeutic effects and changes of pain score, serum uric acid were observed in
      the two groups. RESULTS: The effective rate was 96.4% in the observation group
      and 84.1% in the control group, the former being better than the later (P <
      0.05). Before and after treatment, pain scores were 3.48 +/- 1.05 and 0.94 +/-
      10.85, 3.45 +/- 1.07 and 2.11 +/- 0.91, and serum uric acid contents were (539.16
      +/- 34.49) micromol/L and (376.30 +/- 52.85) micromol/L, and (552.29 +/- 46.15)
      micromol/L and (425.79 +/- 48.69) micromol/L in the two group, respectively.
      After treatment, pain score and serum uric acid content very significantly
      decreased in the two groups (both P < 0.01) and the observation group in the
      analgesic effect and the effect in decreasing serum uric acid content was better
      than the control group (both P < 0.01). CONCLUSION: Electroacupuncture combined
      with local blocking is an effective method for treatment of acute gouty arthritis
      and it can decrease blood uric acid level.

PMID- 18822983
TI  - [Observation on therapeutic effect of low energy He-Ne laser acupoint radiation
      on infantile cold].
AB  - OBJECTIVE: To search for an effective therapy for infantile cold. METHODS: Two
      hundred and fifty-five cases were randomly divided into a laser group (n = 130)
      and a medication group (n = 125). The laser group were treated with lower energy
      He-Ne laser radiation at Tiantu (CV 22), Renying (ST 9), Dazhui (CV 14), Fengmen
      (BL 12), etc. and the medication group were treated mainly with oral
      administration of Amantadine tablets. The therapeutic effect was assessed after
      treatment of 5 days. RESULTS: The laser group in alleviation of cough, nasal
      obstruction, rhinorrhea, sputum sound were significantly better than the
      medication group (P < 0.001, P < 0.01); the cured rate was 68.5% in the laser
      group and 42.4% in the medication group, the former being better than the latter
      (P < 0.001). CONCLUSION: The low energy He-Ne laser acupoint radiation has a
      significant therapeutic effect on infantile cold.

PMID- 18822984
TI  - [Brief introduction of academic thought of ZHU Lian, an expert in modern acup
      moxibustion science].
AB  - ZHU Lian studied medicine from 17 years old and studied acup-moxibustion from
      October 1944. She raised the principle of acupuncture and moxibustion treating
      diseases in the middle period of the last century, "Acupuncture-moxibustion
      mainly stimulates and regulates human nerve system, particularly, regulative
      function and control function of high central nerve system including the cerebral
      cortex, so as to cure diseases". Also, she first put forward 3 keys of
      acupuncture-moxibustion treating diseases, stressed aseptic manipulation, and
      originated a safe needle-retaining method, finger-pressure therapy and maxo roll
      moxibustion; she found 19 new acupoints. Her academic thought of acupuncture and
      moxibustion will become a bridge of integrated Chinese medicine and western
      medicine and will produce inestimable influence on acupuncture and moxibustion
      sciences.

PMID- 18822985
TI  - [Observation on therapeutic effect of acupuncture on complicated facial paralysis
      in the African patient of HIV/AIDS].
AB  - OBJECTIVE: To compare therapeutic effects of acupuncture on complicated facial
      paralysis in the patient with HIV/AIDS and in the patient with no HIV/AIDS.
      METHODS: The observation group of 31 cases of facial paralysis with positive
      HIV/AIDS and the control group of 30 cases of facial paralysis with negative
      HIV/AIDS were treated with acupuncture at Yifeng (TE 17), Xiaguan (ST 7), Jiache
      (ST 6), Taiyang (EX-HN 5), Dicang (ST 4), Yuyao (EX-HN 4), Cuanzhu (BL 2),
      Yingxiang (LI 20), etc. and with individual treatment according to different
      periods of disease. The difference of therapeutic effects between the two groups
      were observed. RESULTS: The effective rate was 83.9% in the observation group and
      96.7% in the control group, with no significant difference between the two
      groups; while the cured rate was 9.7% in the observation group and 73.3% in the
      control group with a very significant difference between the two groups (P <
      0.01). CONCLUSION: Acupuncture with individual treatment has a satisfactory
      therapeutic effect on complicated facial paralysis in the patient of HIV/AIDS.

PMID- 18822986
TI  - [Effects of acupuncture combined with medicine on expression of matrix
      metalloproteinase-2 in the rat of endometriosis].
AB  - OBJECTIVE: To probe into an effective method for treatment of endometriosis (EMs)
      and the mechanism. METHODS: Rat EMs model was established and they were randomly
      divided into a model group, an acup-moxibustion group, a TCM group, an
      acupuncture and medicine group, with a control group set. The acup-moxibustion
      group were treated with electroacupuncture at "Xuehai (SP 10)", "Sanyinjiao (SP
      6)" and moxibustion at "Guanyuan (CV 4)"; the TCM group were treated with stomach
      perfusion of modified Mojie Tablet in normal saline; the acupuncture and medicine
      group were treated with the above two methods; both the control group and the
      model group were bound and treated with stomach perfusion of saline. After
      treatment of 35 days, the greatest diameter of the ectopic tissue was measured in
      the rats, pathological observation of the ectopic tissue was made and matrix
      metalloproteinase-2 (MMP-2) expression in the ectopic tissue was determined.
      RESULTS: The greatest diameter of ectopic tissue and MMP-2 expression in the
      ectopic tissue in the acupuncture and medicine group were significantly lower
      than those in the model group, the acup-moxibustion group and the TCM group (P <
      0.05); and the ectopic endometrium trended to atrophy, and with necrosis of some
      epithelial cells. CONCLUSION: Combination of acupuncture with medicine has a
      better therapeutic effect on endometriosis and down-regulates the abnormal
      increase of MMP-2 level to inhibit the invasion of ectopic tissue to
      extracellular matrix, so as to reduce the ectopic tissue, hence cure of
      endometriosis.

PMID- 18822987
TI  - [Effects of moxibustion and Chinese herbs on contents of mitochondrial DNA, serum
      IL-2 and IL-6 in the aging model rat].
AB  - OBJECTIVE: To probe into the mechanisms of moxibustion and Chinese herbs in
      delaying aging. METHODS: Sixty SD rats were randomly divided into a young control
      group, an aging group, a moxibustion group, a Chinese herb group and a
      moxibustion plus Chinese herb group. In the latter 4 groups, aging rat model was
      established by hypodermic injection of D-galactose. In the course of modeling,
      the 3 treatment group were treated by mild-warm moxibustion at "Zusanli (ST 36)",
      "Shenshu (BL 23)" and "Guanyuan (CV 4)" with reinforcing method, stomach
      perfusion of decoction of Liuwei Dihuang plus Danggui (Angelica) and Danshen
      (Salvia Miltiorrhiza Bge), and the moxibustion plus the Chinese herbs,
      respectively. After treatment for 40 days, liver mitochondrial DNA, serum IL-2
      and IL-6 contents were detected. RESULTS: (1) The mitochondrial DNA content of
      liver cells and serum IL-6 level significantly increased (P < 0.05, P < 0.01) and
      serum IL-2 level significantly decreased (P < 0.05) in the aging model group as
      compared with those in the young control group. (2) The mitochondrial DNA content
      of liver cells and serum IL-6 level significantly decreased (P < 0.05, P < 0.01)
      and serum IL-2 level significantly increased (P < 0.05) in all the treatment
      group as compared with those in the aging model group. CONCLUSION: Moxibustion
      and Chinese herbs function delaying aging though decreasing mitochondrial DNA
      content of liver cells and serum IL-6 level and increasing serum IL-2 level.

PMID- 18822988
TI  - [Thinking about syndrome differentiation-based treatment in clinical acupuncture
      and moxibustion].
AB  - At present, current situation of syndrome differentiation-based treatment in
      clinical acupuncture and moxibustion has brought about concern of scholars at
      home and abroad. Acu-moxibustion doctors on Japan point out that a great number
      of corrupt practice in clinical treatment, which should be paid to enough
      attention. Based on the question put forward by the Japanese doctor, this article
      points out the main existing problems and analyzes some opinions, for which
      people may hold different viewpoints. The "syndrome differentiation-based
      treatment" is embodied in the scientific and orderly application of "principles,
      methods, prescriptions, acupoints and techniques" in the clinical practice. To
      achieve the purpose of improving the therapeutic effect, the clinical techniques,
      action regularity, indications and influential factors, etc. should further be
      studied.

PMID- 18822989
TI  - [Discussion on the national standard, the Name and Location of Acupoints].
AB  - Location of a part of acupoints in the national standard, The Name and Location
      of Acupoints, are studied. In combination with anatomy, record of ancient
      literature and teaching experience, the location of Naohui (TE 13), Chengshan (BL
      57), Fengshi (GB 31), Zhongdu (GB 32), Toulinqi (GB 15), Yinbao (LR 9) and
      Shaoshang (LU 11) in the national standard are analyzed and the relative location
      methods are raised.

PMID- 18822990
TI  - [Textual research on the twelve divergent meridians].
AB  - Checking of divergent meridians in the development course of meridian theories
      shows that these are remains of meridian theories of the eleven meridians model,
      expressing relation of yang meridians to zang-fu organs, and yin and yang
      meridians having a certain common characters, which are components of twelve
      meridians before Lingshu : Meridians. Modern expressions of meridian system
      confuse its relation with theory of twelve meridians in Lingshu : Meridians.

PMID- 18822991
TI  - [Contribution of teacher MEI Jian-Han to modern acup-moxibustion science].
AB  - Acup-moxibustion experts are indispensable for probing into establishment of
      modern higher education and academic system of acupuncture and moxibustion. Among
      them, teacher MEI made a great distribution, mainly including: summarizing the
      outline of indications of acupoints of 14 channels, raising making prescription
      law of acupoints and indications law of acupoints, expounding the relationship
      between channels running and disease symptoms, summing up characteristics of
      theories of the twelve divergent meridians and the twelve muscle regions, drawing
      an indications diagram of acupoints of the 14 meridians and a schematic diagram
      of relation between the running of meridians and disease symptoms, a schematic
      diagram of running of the twelve divergent meridians, and a diagram of the
      relations between running of the twelve muscle regions and disease symptoms,
      inventing acupoint location method with finger-equal division, expounding
      Xiaheshu, simplifying the calculation of Ziwuliuzhu and inventing a calculation
      scale and simple acupoints selection table. In his later years, he systematically
      studied on the theories of eight extra meridians and clinical application, and
      raised theorem of meridians, etc.

PMID- 18822992
TI  - [Advances of studies on acupuncture reinforcing-reducing of twirling-rotating the
      needle].
AB  - The theories and clinical and experimental studies about reinforcing-reducing
      manipulation of twirling rotating the needle in recent 15 years are reviewed and
      a brief account of manipulation methods, mechanisms and effects of reinforcing
      reducing manipulation of twirling-rotating the needle is given, and it is
      indicated that the following several aspects in the studies at present need to be
      completed. Standardization and establishment of national standard of acupuncture
      manipulation must be enforced; quantitative parameters of acupuncture
      manipulation and mechanisms of acupuncture reinforcing-reducing of twirling
      rotating the needle need to be further studied.

PMID- 18822993
TI  - Leadership in mental health nursing.

PMID- 18822994
TI  - Focus on compassion.

PMID- 18822995
TI  - Gender bias in domestic violence?

PMID- 18822996
TI  - Sequenced Treatment Alternatives to Relieve Depression (STAR*D). Part 1: study
      design.
AB  - This article describes the design of the Sequenced Treatment Alternatives to
      Relieve Depression (STAR*D) study. The main study objective was to compare the
      efficacy and tolerability of various antidepressant therapies through four
      sequential treatment levels. To maximize the generalizability of the results,
      broad inclusion and minimal exclusion criteria were used to recruit patients with
      major depression from a large number of real-world settings. The goal of
      treatment was to achieve full remission. A measurement-based care system was used
      to guide and optimize treatment at each level. Patients were treated for up to 12
      weeks at each level (with an optional week 14 visit, if needed). All patients
      started with citalopram at Level 1. The three subsequent levels of treatment
      options were randomized and open label, and patients could accept or decline
      treatments as long as sufficient options were left that allowed randomization
      between at least two different options. For any treatment level, patients who
      reached full remission, and those with satisfactory response, could continue the
      same treatment during 1-year naturalistic follow up. Patients who did not reach
      full remission were encouraged to enter subsequent levels.

PMID- 18822997
TI  - Remembering: forget about forgetting and train your brain instead.
AB  - As people age, they often become increasingly concerned about their inability to
      remember names and faces or recall specific words. As their memory seems to
      decline, they worry about developing Alzheimer's disease. Yet, new research
      suggests that for most aging adults, failing to remember is because of an
      overload of information and difficulty in trying to sort through a cluttered
      "database." Brain-training programs based on evolving research, as well as
      increased opportunities to reflect on healthy aging experiences, offer important
      possibilities for working with clients concerned about memory problems.

PMID- 18822998
TI  - Behavioral health staff's perceptions of pet-assisted therapy: an exploratory
      study.
AB  - The purpose and objectives of this exploratory descriptive study were threefold:
      to assess the impact of pet-assisted therapy on the overall well-being of
      behavioral health staff, to document whether pet-assisted therapy affected the
      retention of behavioral health staff, and to explore and describe therapeutic
      measures behavioral health staff implemented in using pet-assisted therapy in the
      delivery of mental health patient care. The participants in this study were 10
      behavioral health staff members who were involved with the pet-assisted therapy
      program at a private psychiatric hospital in a Chicago suburb. Themes that
      emerged from the study included Self-Awareness, Morale, Innovative Therapeutic
      Strategies, Challenges, and Future Directions. This article describes these
      themes in detail, provides quotations from participants to further highlight
      meaning, and discusses the powerful effect of pet-assisted therapy on both
      patients and staff in the therapeutic milieu.

PMID- 18822999
TI  - Cyber child sexual exploitation.
AB  - A 2-year review of 285 child cyber crime cases reported in the newspaper revealed
      how the Internet offenders were apprehended, the content of child pornography,
      and crime classification. A subsample of 100 cases with data on offender
      occupation revealed 73% of cases involved people in positions of authority. The
      dynamics of child cyber crime cases direct the implications for nursing practice
      in terms of evidence-based suspicion for reporting, categorizing the content of
      Internet images, referral of children for counseling, and treatment of offenders.

PMID- 18823000
TI  - Web-based treatment of alcohol problems among rural women.
AB  - It is estimated that 6 million women in the United States misuse alcohol. Of that
      number, many live in rural areas and face numerous barriers to treatment. The
      World Wide Web has the potential to help such individuals overcome these
      barriers. In light of emergent findings supporting the effectiveness of online
      alcohol treatment services for women, a randomized pilot study was conducted to
      evaluate a Web-based, self-guided alcohol treatment program. Eligible women were
      randomized to standard care or an online treatment program. Web-based treatment
      components included gender-specific reference modules and decision making
      modules, an asynchronous bulletin board, and a synchronous chat feature. The
      average age of the participants (N = 44) was 50 (SD = 11 years), and their
      baseline Alcohol Use Disorders Identification Test score was 18 (SD = 6), with 8
      being the cut-off score for problem drinking. At 3-month follow up, both
      treatment groups decreased their drinking; however, no significant differences
      were found between them.

PMID- 18823001
TI  - MRT letter: full-tilt electron tomography with a piezo-actuated rotary drive.
AB  - Piezoelectric nanoactuation, which is rapidly becoming established as state-of
      the-art positioning control in transmission electron microscopy (TEM), is
      extended here to include a rotational degree of freedom. A piezoelectric
      goniometer with both translational and rotary drive action has been designed with
      high level of miniaturization to fit into a standard TEM specimen holder shaft
      without compromising any of the performance of the default TEM goniometer and
      without any modifications to the TEM. Enhanced functionality of such a goniometer
      in-goniometer is outlined and experimental results for electron tomography of
      nanostructures over a full tilt range of views, without any missing angles, are
      demonstrated.

PMID- 18823002
TI  - Types and numbers of sensilla on antennae and maxillary palps of small and large
      houseflies, Musca domestica (Diptera, Muscidae).
AB  - Houseflies, Musca domestica, obtained from a high-larval-density culture were
      significantly (ca. 1.5 times) smaller than those from a low-larval-density
      culture. The same held true for their antennae and maxillary palps. Structure,
      number, and distribution of sensilla on antennae and palps of small and large
      flies were investigated using Scanning electron microscopy and Transmission
      electron microscopy. In each funiculus three pits were present, two (Type I)
      consisting of several compartments and one (Type II) of one compartment. Four
      types of olfactory sensilla were detected: trichoid sensilla on the funiculi,
      basiconic sensilla on funiculi and palps, grooved sensilla on funiculi and in
      pits Type I, and clavate sensilla on funiculi and in pits Type II. Type I pits
      also contained striated sensilla (presumably hygroreceptors). Mechanosensory
      bristles were present on scapes, pedicels, and palps. Noninnervated microtrichia
      were found on the palps and all antennal segments. The large houseflies possessed
      nearly twice as much sensilla as the small flies. So far, we did not observe
      differences in behavior between small and large flies. We assumed that small
      flies, being olfactory less equipped than large flies, may be able to compensate
      for this by, e.g., visual cues or by their olfactory sensilla being more
      sensitive than those of large flies. To be able to answer these questions careful
      studies have to be done on the behavioral responses of small and large flies to
      environmental stimuli. In addition, electrophysiological studies should be
      performed to reveal whether the responses of individual sensilla of flies reared
      under different conditions have been changed.

PMID- 18823003
TI  - Assessment of mitochondrial toxicity by analysis of mitochondrial protein
      expression in mononuclear cells.
AB  - BACKGROUND: Real-time PCR has quantified decreased mitochondrial DNA levels in
      association with nucleoside reverse transcriptase inhibitor (NRTI) therapy of HIV
      infected populations. However, real-time PCR is best suited to distinguish log
      differences in an analyte. In an effort to monitor individuals in more detail, we
      developed a flow cytometric assay to gauge mitochondrial function. METHODS: Flow
      cytometric quantification of a mitochondrial DNA-encoded mitochondrial protein
      (cytochrome c oxidase subunit I (COX-I)) and a nuclear DNA-encoded mitochondrial
      protein [ATP synthase subunit D (Sub-D)] was optimized and validated. RESULTS:
      Intra-assay and interassay variability was low using peripheral blood mononuclear
      cells (PBMCs) (CV of 6.15% for COX-I and 7.11% Sub-D, and 9.38% and 9.83% for COX
      I and Sub-D, respectively). Mitochondrial protein depletion was evident with in
      vitro treatment of cells with ethidium bromide (EtBr) and zalcitabine (ddC).
      Mitochondrial protein expression in 40 healthy adults clustered tightly.
      Depletion of mitochondrial protein, however, was neither detected in
      cryopreserved PBMC from NRTI-treated children (n = 9) nor in adults with a
      history of symptoms consistent with mitochondrial toxicity or ongoing treatment
      with didanosine (ddI) or stavudine (d4T) (n = 51). CONCLUSIONS: A validated flow
      cytometric assay allows simultaneous detection of mitochondrial DNA and nuclear
      DNA encoded proteins at the single cell level, offering a method to monitor for
      mitochondrial function. Prospective studies are required to evaluate whether
      mitochondrial protein loss is observed in at-risk patients prior to the onset of
      symptoms from mitochondrial dysfunction.

PMID- 18823004
TI  - Preparation, characterization, and evaluation of radiopaque hydrogel filaments
      for endovascular embolization.
AB  - Radiopaque hydrogel filaments were prepared, characterized, and evaluated for
      potential use as implants for endovascular embolization of vascular defects.
      Three hydrogel formulations were prepared by free radical polymerization: (i)
      poly(ethylene glycol) diacrylate with 2,4,6-triiodophenyl penta-4-enoate (PEG-I),
      (ii) poly(ethylene glycol) diacrylamide with barium sulfate (PEG-B), and (iii)
      poly(propylene glycol) diacrylate with barium sulfate (PPG-B). The PEG-B and PPG
      B hydrogels exhibited radiopacity comparable with clinically used platinum coils,
      whereas the PEG-I hydrogel did not. In the dry state, the average ultimate
      tensile strength and strain of the hydrogels ranged from 37 to 128 gf and 21% to
      72%, respectively. The PEG-B hydrogel had significantly higher tensile strength
      compared with the PEG-I hydrogel. In the hydrated state, the average ultimate
      tensile strength and strain ranged from 5 to 15 gf and 7% to 30%, respectively.
      Statistically significant differences in tensile strength were not present when
      hydrated. Compared with poly(ethylene) after 4-week implantation into the
      subcutaneous space of rabbits, the PEG-I hydrogel elicited slightly more
      inflammation, whereas the PEG-B and PPG-B hydrogels elicited less inflammation.
      All three hydrogel formulations elicited less fibrous encapsulation than
      poly(ethylene). With further development, these materials have potential as
      embolization devices.

PMID- 18823005
TI  - A comparison of multiplex suspension array large-panel kits for profiling
      cytokines and chemokines in rheumatoid arthritis patients.
AB  - BACKGROUND: Multiplex analysis allows measurements of a large number of analytes
      simultaneously in each sample. On the basis of the Luminex multiplex technology
      (xMAP), kits for measuring multiple cytokines and chemokines (immunomodulators)
      are commercially available and are useful in investigations on inflammatory
      diseases. This study evaluated four multiplex kits (Bio-Plex, LINCOplex,
      Fluorokine, and Beadlyte) that contained 27, 29, 20, and 22 analytes each,
      respectively, for the analysis of immunomodulators in plasma of patients with
      rheumatoid arthritis (RA) who underwent treatment with antibody against CD20
      (rituximab), a B-cell reductive therapy. METHODS: Multiplex kits were tested on
      serial plasma samples obtained from six RA patients at baseline and multiple time
      points (3, 6, and 9 months) post-treatment with rituximab. The RA patients
      included in this study had previously failed therapy with disease modifying anti
      arthritis drugs (DMARD) and treatment with anti-TNFalpha antibody (infliximab).
      RESULTS: Computer modeling and hierarchical cluster analysis of the multiplex
      data allowed a comparison of the performance of multiplex assay kits and revealed
      profiles of immunomodulators in the RA patients. CONCLUSIONS: In plasma of RA
      patients who appeared to have benefited from the rituximab treatment, the profile
      of significantly elevated immunomodulators by at least two of the three kits
      (BioPlex, LINCOplex, Beadlyte) is as follows: IL-12p70, Eotaxin, IL-4, TNFalpha,
      Il-9, IL-1beta, IFNgamma, IL-10, IL-6, and IL-13. Immunomodulator profiling by
      multiplex analysis may provide useful plasma biomarkers for monitoring response
      to B-cell reductive therapy in RA patients.

PMID- 18823006
TI  - Microspheres made by w/o/o emulsion method with reduced initial burst for long
      term delivery of endostar, a novel recombinant human endostatin.
AB  - The purpose of this work is to design biodegradable Poly(lactide-co-glycolide)
      (PLGA) microspheres with low initial burst for sustained delivery of Endostar (a
      novel recombinant human endostatin) and investigate effects of PLGA molecular
      weight and composition on the release behavior of Endostar microspheres. Endostar
      microspheres were prepared by using novel w/o/o multiple emulsification
      evaporation technique. Effects of polymer molecular weight and copolymer
      composition on particle properties and release behavior (in vitro and in vivo)
      have been reported. Drug release in vitro decreased with increase in molecular
      weight and lactide content of PLGA. Zero order release and low initial burst were
      obtained with all microsphere formulations. The in vivo performance of Endostar
      microspheres were also found to be dependent on the polymer molecular weight and
      copolymer composition. Together, these results suggest that the initial burst
      release can be reduced by w/o/o emulsion method and the release of Endostar can
      be changed significantly by varying the polymer molecular weight and copolymer
      composition.

PMID- 18823007
TI  - Automatic quantification of histological studies in allergic asthma.
AB  - The evaluation of new therapies to treat allergic asthma makes frequent use of
      histological studies. Some of them are based on microscope observation of stained
      paraffin lung sections to quantify cellular infiltrate, an effect directly
      related to allergic processes. Currently, there is no software tool available for
      doing this quantification automatically. This paper presents a methodology and a
      software tool for the quantification of cellular infiltrate in lung tissue images
      in an allergic asthma mouse model. The image is divided into regions of equal
      size, which are then classified by means of a segmentation algorithm based on
      texture analysis. The classification uses three discriminant functions, built
      from parameters derived from the histogram and the co-occurrence matrix. These
      functions were calculated by means of a stepwise discriminant analysis on 79
      samples from a training set. Results provided a correct classification of 96.8%
      on an independent test set of 251 samples labeled manually. Regression analysis
      showed a good agreement between automatic and manual methods. A reliable and easy
      to implement method has been developed to provide an automatic method for
      quantifying microscopy images of lung histological studies. Results showed
      similar accuracy to that provided by an expert, while allowing analyzing a much
      larger number of fields in a repeatable way.

PMID- 18823008
TI  - How to minimize formation and growth of tumours: potential benefits of decapod
      crustaceans for cancer research.
AB  - Tumours have only rarely been observed in the decapod crustaceans, a large animal
      group of more than 10,000 species that includes the commercially important and
      well investigated shrimp, lobsters, crayfish and crabs. Analysis of the
      literature and information from cancer and diseases data bases revealed a total
      of 15 incidences, some of them being questionable. Even in the long-lived
      species, which can reach life spans of almost 100 years, neoplasias are virtually
      unknown. The data published so far suggest that the strikingly different
      frequencies of carcinogenesis between decapods and other well investigated animal
      groups like mammals, fish, insects and molluscs is based on differences of the
      metabolic pathways for carcinogens, the immune systems, and the regulation of
      stem cells. Therefore, representatives of the Decapoda may serve as useful models
      to study how organisms can successfully prevent or control spontaneously and
      environmentally induced cell proliferation. A particularly promising candidate
      for in-depth investigation of these topics is the marbled crayfish, a rather new
      clonal lineage that is presently being introduced as a laboratory model in
      development and epigenetics.

PMID- 18823009
TI  - Exploring the cost-effectiveness of Helicobacter pylori screening to prevent
      gastric cancer in China in anticipation of clinical trial results.
AB  - Gastric cancer is the second leading cause of cancer-related deaths worldwide.
      Treatment for Helicobacter pylori infection, the leading causal risk factor, can
      reduce disease progression, but the long-term impact on cancer incidence is
      uncertain. Using the best available data, we estimated the potential health
      benefits and economic consequences associated with H. pylori screening in a high
      risk region of China. An empirically calibrated model of gastric cancer was used
      to project reduction in lifetime cancer risk, life-expectancy and costs
      associated with (i) single lifetime screening (age 20, 30 or 40); (ii) single
      lifetime screening followed by rescreening individuals with negative results and
      (iii) universal treatment for H. pylori (age 20, 30 or 40). Data were from the
      published literature and national and international databases. Screening and
      treatment for H. pylori at age 20 reduced the mean lifetime cancer risk by 14.5%
      (men) to 26.6% (women) and cost less than $1,500 per year of life saved (YLS)
      compared to no screening. Rescreening individuals with negative results and
      targeting older ages was less cost-effective. Universal treatment prevented an
      additional 1.5% to 2.3% of risk reduction, but incremental cost-effectiveness
      ratios exceeded $2,500 per YLS. Screening young adults for H. pylori could
      prevent one in every 4 to 6 cases of gastric cancer in China and would be
      considered cost-effective using the GDP per capita threshold. These results
      illustrate the potential promise of a gastric cancer screening program and
      provide rationale for urgent clinical studies to move the prevention agenda
      forward.

PMID- 18823010
TI  - Elevation of seprase expression and promotion of an invasive phenotype by
      collagenous matrices in ovarian tumor cells.
AB  - Tumor cells do not constitutively exhibit invasive activity, but rather, can be
      transiently induced to adhere and form lesions. We report here that the
      expression of seprase, a dominant EDTA-resistant gelatinase in malignant tumors,
      is dependent on tumor cell exposure to type I collagen gel (TICg). The induced
      seprase expression of ovarian tumor cells influences their collagen contraction
      and invasion capability. Importantly, tumor cells with reduced seprase
      expression, due to manipulation by RNA interference, showed a reduction of TICg
      contraction in the gel contractility assay, inhibition of tumor cell invasion
      through TICg as shown by a transwell migration assay and inhibition of peritoneal
      membrane tumor lesion in a mouse model. In addition, mAb C27, an antibody against
      beta1 integrin, which blocks cellular avidity to TICg, can induce seprase RNA
      expression and promote the invasive phenotype and metastatic potential of ovarian
      tumor cells. Thus, collagenous matrices in the tumor cell niche induce the
      expression of seprase and initiate tumor invasion and metastatic cascades.

PMID- 18823011
TI  - Hypomethylation of retrotransposable elements correlates with genomic instability
      in non-small cell lung cancer.
AB  - LINE-1 and Alu elements are non-LTR retrotransposons, constituting together over
      30% of the human genome and they are frequently hypomethylated in human tumors. A
      relationship between global hypomethylation and genomic instability has been
      shown, however, there is little evidence to suggest active role for
      hypomethylation-mediated reactivation of retroelements in human cancer. In our
      study, we examined by Pyrosequencing the methylation levels of LINE-1 and Alu
      sequences in 48 primary nonsmall cell carcinomas and their paired adjacent
      tissues. We demonstrate a significant reduction of the methylation levels of both
      elements (p = 7.7 x 10(-14) and 9.6 x 10(-7), respectively). The methylation
      indices of the 2 elements correlated (p = 0.006), suggesting a possible common
      mechanism for their methylation maintenance. Genomic instability was measured
      utilizing 11 fluorescent microsatellite markers located on lung cancer hot-spot
      regions such as 3p, 5q 9p, 13q and 17p. Hypomethylation of both transposable
      elements was associated with increased genomic instability (LINE, p = 7.1 x 10(
      5); Alu, p = 0.008). The reduction of the methylation index of LINE-1 and Alu
      following treatment of 3 lung cell lines with 5-aza-2'-deoxycitidine,
      consistently resulted in increased expression of both elements. Our study
      demonstrates the strong link between hypomethylation of transposable elements
      with genomic instability in non-small cell lung cancer and provides early
      evidence for a potential active role of these elements in lung neoplasia. As
      demethylating agents are now entering lung cancer trials, it is imperative to
      gain a greater insight into the potential reactivation of silent retrotransposons
      in order to advance for the clinical utilization of epigenetics in cancer
      therapy.

PMID- 18823012
TI  - Mechanistic evaluation of alginate-HEC gelisphere compacts for controlled
      intrastriatal nicotine release in Parkinson's disease.
AB  - This study focused on elucidating a mechanistic understanding in support of the
      multiple mechanisms which govern the formation of crosslinked alginate
      hydroxyethylcellulose (Alg-HEC) gelispheres intended for the controlled
      intrastriatal release of nicotine as a neuroprotectant in Parkinson's Disease.
      HEC was incorporated as a reinforcing "protective" colloidal polymer to induce
      interactions between the free carboxyl groups of alginate with hydroxylated HEC
      monomers. Gelispheres were compressed within an external poly(lactic-co-glycolic
      acid) (PLGA) matrix to further prolong the release of nicotine. Sol-gel
      interconversion mechanisms, matrix deformability moduli, matrix fracture energies
      and chemometric models of the associated energy paradigms were analyzed for their
      influence on the mechanism and extent of nicotine release. Textural profiling
      demonstrated higher fracture energies (7.94-26.69 x 10(-4) J) and lower
      deformability moduli (12.24-58.36 N/mm) when gelispheres were cured in 2 M HCl as
      a postcuring step. Ba(2+) crosslinked gelispheres resulted in superiorly compact
      matrices with an increase in volume of 201-329% as compared to the Ca(2+) and
      Zn(2+) crosslinked matrices. The order of matrix compactness was as follows:
      Zn(2+) < Ca(2+) < Ba(2+). Molecular mechanisms of formation, interaction,
      conversion, and stability of sol-gel transitions depended on the type of
      crosslinker, crosslinking time, energy transactions, and interactions with
      molecules of the hydration medium. Ba(2+) crosslinked gelispheres released
      nicotine slower than Ca(2+) and Zn(2+) crosslinked gelispheres due to the higher
      energy requirement for interconversion to sol while the energy requirements for
      Ca(2+) and Zn(2+) was at a lower demand. Ba(2+) crosslinked gelispheres within
      PLGA matrices therefore retarded nicotine release in a pseudo-zero-order manner
      over 21 days.

PMID- 18823013
TI  - Freeze-dry microscopy of protein/sugar mixtures: drying behavior, interpretation
      of collapse temperatures and a comparison to corresponding glass transition data.
AB  - The purpose of this study is to investigate the change in collapse appearance and
      temperature of protein/sugar mixtures as a function of nucleation temperature
      (T(n)), sublimation velocity (V(sub)) and the sugar/protein mole ratio when
      performing freeze-dry microscopy experiments. BSA and HSA were used as sample
      proteins and mixed with either sucrose or trehalose. Differential scanning
      calorimetry was used to determine the corresponding glass transition temperatures
      (T'g). To allow a more representative comparison between these analytical
      methods, a collapse midpoint temperature (T(c-50)) was introduced. While there
      was no distinct correlation between T(n) and the onset of collapse (T(oc)) for
      either mixture, V(sub) was found to correlate with the measured collapse
      temperature which is important for comparability of experiments. Furthermore,
      V(sub) could be used to qualitatively investigate the product resistance to water
      vapor flow. A dramatic change in the appearance of collapse was found for high
      sugar/protein mole ratios (> or =362:1) which needs to be considered to avoid a
      misinterpretation of T(oc) data. At low protein concentrations midpoint T'g data
      showed good agreement with T(oc) values but were found significantly lower at
      higher protein concentrations. Application of the Gordon-Taylor equation failed
      to predict the critical temperature for any of the protein/sugar mixtures
      studied.

PMID- 18823014
TI  - Spectrum of movement disorders associated with glutaric aciduria type 1: a study
      of 16 patients.
AB  - Glutaric aciduria type 1 (GA1) is an autosomal recessive neurometabolic disorder
      due to glutaryl CoA dehydrogenase deficiency. Comprehensive descriptions of GA1
      associated movement disorders are rare. In order to refine the description of the
      motor phenotype, we prospectively studied 16 consecutive pediatric and adult GA1
      patients, focusing on the movement disorders and their time course. In most
      patients, generalized dystonia, superimposed on baseline axial hypotonia,
      remained the predominant feature throughout the disease course. With aging, it
      tended to evolve from mobile to fixed dystonia and to be associated with akinetic
      rigid parkinsonism. Prominent orofacial involvement was a consistent feature in
      GA1 patients with movement disorders, resulting in speech disorders with features
      of combined hyperkinetic dysarthria and speech apraxia. The types and outcome of
      movement disorders in this setting should be taken into consideration during
      rehabilitation and for patient selection and evaluation in therapeutic trials.

PMID- 18823015
TI  - TENS for the treatment of propriospinal myoclonus.

PMID- 18823016
TI  - Liquid high concentration IgG1 antibody formulations by precipitation.
AB  - A manufacturing approach for liquid high concentration antibody formulations
      based on precipitation and subsequent re-dissolution was investigated. IgG1
      antibody solutions were concentrated from 20 to 100 mg/mL by intermediate
      precipitation, with a recovery exceeding 95%, retention of the native secondary
      structure and binding activity as well as adequate stability. Quantitative,
      reproducible precipitation was performed using 1.45 M ammonium sulphate (pH 5.5
      and 8.0), 0.67 M sodium citrate (pH 8.0) and 9% (w/v) PEG 4000 (pH 5.5 and 8.0).
      Scalability was confirmed from 1 to 100 mL. The concentrations achievable in the
      re-dissolution step were less affected by the re-dissolution medium, but limited
      by the residual precipitant. Both, improved removal of remaining precipitant
      liquid and larger precipitation scales were successful in increasing the final
      protein concentration. SEC and turbidity analysis directly after re-dissolution
      indicated that similar protein qualities were obtained, independent from the
      precipitant used. However, increased aggregate formation was observed after short
      term storage of the precipitated protein particles at either 2-8 degrees C or
      ambient temperature. An accelerated mechanical and thermal stability program
      verified comparable stability of the re-dissolved liquid 100 mg/mL formulations
      produced by intermediate precipitation to a control formulation obtained by
      standard ultrafiltration.

PMID- 18823017
TI  - Frequency dependence of viscoelastic properties of medical grade silicones.
AB  - Cylinders of medical grade silicone elastomers, (29 mm in diameter and 13 mm
      thick), immersed in physiological saline solution at 37 degrees C, were
      investigated by dynamic mechanical analysis (DMA). A sinusoidal cyclic
      compression of 40 +/- 5 N was applied over a frequency range, f, of 0.02-100 Hz.
      Values of the storage, E', and loss, E'', moduli for the cylinders were found to
      depend on f; the dependence of E' or E'' on the logarithm (base 10) of f was
      represented by a third-order polynomial. Above about 0.3 Hz, the cylindrical
      specimens appeared to be undergoing the onset of a transition from the rubbery to
      the glassy state. There was no significant difference between results obtained at
      37 and 23 degrees C; pretreatment of specimens in physiological saline at 37
      degrees C for 24 h and 29 days had no appreciable effect on the results.

PMID- 18823018
TI  - Magnetic resonance imaging identifies multifocal and multicentric disease in
      breast cancer patients who are eligible for partial breast irradiation.
AB  - BACKGROUND: In this retrospective study, the authors hypothesized that magnetic
      resonance imaging (MRI) would alter partial breast irradiation (PBI) eligibility
      by identifying cancers outside the PBI volume compared with mammography alone.
      METHODS: Since 2002, MRI was used nonselectively at the authors' institution for
      the staging of patients with nonmetastatic breast cancer. Of 450 consecutive
      patients with invasive breast cancer, 110 patients who were eligible for PBI were
      identified by using criteria outlined by National Surgical Adjuvant Breast and
      Bowel Project B-39/Radiation Oncology Group trial 0413 based on mammography,
      ultrasonography, and initial pathology. In that trial, patients were randomized
      (stage I/II invasive cancers that measured <or=3 cm and <or=3 positive lymph
      nodes) to receive either whole-breast radiotherapy or PBI. MRI reports were
      reviewed to determine whether MRI identified secondary lesions 1) within the same
      quadrant (multifocal), 2) in a different quadrant (multicentric), or 3) in the
      contralateral breast. These lesions were pathologically proven carcinoma and
      would have rendered the patient ineligible for PBI. RESULTS: MRI identified
      secondary lesions in 10% of patients (95% confidence interval [CI], 4.4%-15.6%).
      Multifocal disease was identified in 3.6% (95% CI, 1.4%-9%), multicentric disease
      was identified in 4.5% (95% CI, 2%-10.2%), and contralateral disease was
      identified in 1.8% (95% CI, 0.5%-6.4%). The proportion of patients with false
      positive MRI findings was 4.5% (95% CI, 2%-10.2%). The positive predictive value
      of MRI was 72.2% (95% CI, 46.4%-89.3%). CONCLUSIONS: MRI identified frequent
      secondary cancers that would not be removed routinely by surgery or targeted in
      the radiation field if treated with PBI. The current data suggest that MRI should
      be considered to assess PBI eligibility to minimize potential local failures.

PMID- 18823019
TI  - Effects of simulated functional loading conditions on dentin, composite, and
      laminate structures.
AB  - Use of composite restorations continues to increase, tempered by more potential
      problems when placed in posterior dentition. Thus, it is essential to understand
      how these materials function under stress-bearing clinical conditions. Because
      mastication is difficult to replicate in the laboratory, cyclic loading is
      frequently used within in vitro evaluations but often employs traditional fatigue
      testing, which typically does not simulate occlusal loading because higher
      stresses and loading frequencies are used, so failure mechanisms may be
      different. This investigation utilized relevant parameters (specimen size,
      loading frequency) to assess the effects of cyclic loading on flexural mechanical
      properties and fracture morphology of (coronal) dentin, composite, and dentin
      adhesive-composite "laminate" structures. Incremental monitoring of flexural
      modulus on individual beams over 60,000 loading cycles revealed a gradual
      increase across materials; post hoc comparisons indicated statistical
      significance only for 1 versus 60k cycles. Paired specimens were tested (one
      exposed to 60k loading cycles, one to static loading only), and comparisons of
      flexural modulus and strength showed statistically significantly higher values
      for cyclically loaded specimens across materials, with no observable differences
      in fracture morphology. Localized reorganization of dentin collagen and polymer
      chains could have increased flexural modulus and strength during cyclic loading,
      which may have implications toward the life and failure mechanisms of clinical
      restorations and underlying tooth structure.

PMID- 18823020
TI  - Properties of antibiotic-loaded acrylic bone cements for use in cemented
      arthroplasties: a state-of-the-art review.
AB  - Infection of periprosthetic sites of total joint replacements has been widely
      reported. Although, by most accounts, the incidence of such events is low, the
      problem can prove to be expensive to remedy. In the case of cemented
      arthroplasties, a common management modality is the use of antibiotic-loaded
      acrylic bone cement (ALABC) as a prophylaxis or a therapeutic agent. Although
      there is a large literature on properties of ALABCs (on the order of 100 journal
      articles), a comprehensive review is lacking. The present contribution, whose
      objective is to fill this gap, is organized in four parts. Details of the
      background to and motivation for the work are given in the first part,
      explicative summaries of literature studies on the influence of various factors
      on an array of in vitro and in vivo properties of ALABCs are covered in the
      second part, issues and areas for future studies are presented in the third part,
      and the fourth part contains a summary of the most salient points made in the
      review.

PMID- 18823021
TI  - Cephalexin-loaded injectable macroporous calcium phosphate bone cement.
AB  - Different types of calcium phosphate cements (CPCs) have been studied as
      potential matrices for incorporating different types of antibiotics. All of these
      matrices were morphologically microporous whereas macroporosity is essential for
      rapid cement resorption and bone replacement. In this study, liberation of
      cephalexin monohydrate (CMH) from a macroporous CPC was investigated over 0.5-300
      h in simulated body fluid and some mathematical models were fitted to the release
      profiles. Macroporosity was introduced into the cement matrix by using sodium
      dodecyl sulfate molecules as air-entraining agents and the effect of both
      surfactant and CMH on basic properties of the CPC was studied. Incorporation of
      CMH into the CPC composition increased the setting time, decreased the
      crystallinity of the formed apatite phase, and improved the injectability of the
      paste. The use of both CMH and sodium dodecyl sulfate did not affect the rate of
      conversion of the reactants into apatite phase while soaking the cements in
      simulated body fluid. Results showed that the liberation rate of the drug from
      porous CPC was higher than that of the nonporous CPC but same release patterns
      were experienced in both types of cements, that is, like to nonporous CPC, a time
      dependent controlled release of the incorporated drug was obtained from
      macroporous CPC. The Weibull model was the best fitting-equation for release
      profiles of all cements. The liberated CMH was as active as fresh cephalexin. It
      is concluded that this macroporous CPC can be successfully used as drug carrier
      with controlled release profile for the treatment of bone infections.

PMID- 18823022
TI  - In-situ sol-gel synthesis and characterization of bioactive pHEMA/SiO2 blend
      hybrids.
AB  - A novel procedure to synthesize poly(2-hydroxyethylmethacrylate)-silica blend
      hybrids is presented. Methacrylate monomers bearing an alkoxysilyl unit, prepared
      by Michael addition of 2-hydroxyethylmethacrylate (HEMA) to 3
      Aminopropyltriethoxysilane (APTS) were employed. By (13)C NMR and mass analysis
      it was possible to establish the formation of coupling hybrid species. Hybrid
      materials, with final concentration ranging from 10% to 30% w/w of silica gel to
      the mass of polymer, were obtained through basic catalyzed sol-gel process of
      tetraethoxysilane (TEOS) and the alkoxysilyl unit of the hybrid monomer, followed
      by in-situ free-radical polymerization. The hybrids were characterized as far as
      concerns their thermal properties (glass transition temperature, decomposition
      temperature), their sorption behavior in water, and in-vitro bioactivity. Optical
      transparency, higher glass transition temperature, and higher decomposition
      temperature than pHEMA suggest an increase in either density or intensity of
      cross-links between the organic and the inorganic phases. The swelling ratio of
      the 30% hybrids is comparable to pHEMA, whereas it is lower for the other
      compositions. In-vitro bioactivity of the hybrids, due to the inorganic phase,
      was ascertained. Soaking time required for apatite deposition on the samples
      surface decreases as the content of silica gel increases. Therefore, the obtained
      bioactive hybrids can be used to make bioactive scaffolds for bone engineering.

PMID- 18823023
TI  - Controlled release of complexed DNA from polycaprolactone film: comparison of
      lipoplex and polyplex release.
AB  - This report investigates the comparative in vitro controlled release and
      transfection efficiencies of pDNA-lipofectamine complex (lipoplex) and pDNA
      poly(ethylene imine) complex (polyplex), from a biodegradable polycaprolactone
      (PCL) film. The effect of molecular weight of gelatin used as a porogen on in
      vitro release and transfection efficiency was also studied. A sustained release
      profile was obtained for naked pDNA and lipoplex from polymeric films for a
      month, while the release of polyplexes (PEI/DNA) is simply a burst at day 5, with
      little or no release thereafter. The release of polyplexes from PCL films is
      retarded due to interaction between the polyplexes and the polymer. A high burst
      release was seen for naked pDNA which was suppressed in the presence of gelatin.
      The extent of suppression of the burst effect by gelatin increased with its
      molecular weight. For complexed pDNA (lipoplex), the release was slow, but could
      be accelerated using gelatin; again the acceleration in release is dependant on
      the molecular weight of the gelatin used. The addition of gelatin as a porogen
      has no effect on the release of polyplexes from PCL films. The bioactivity of
      released plasmid DNA and complexes was studied by in vitro transfection using COS
      7 cells. Transfection was observed from released lipoplexes samples till day 9
      from PCL film with lower MW gelatin and till day 18 in the case of PCL films with
      higher MW gelatin. The results also showed that the bioactivity of released
      lipoplexes was superior to that of the naked pDNA.

PMID- 18823024
TI  - A randomized phase II trial of adjuvant chemotherapy with uracil/tegafur and
      gemcitabine versus gemcitabine alone in patients with resected pancreatic cancer.
AB  - BACKGROUND: There have been few randomized studies of adjuvant chemotherapy using
      gemcitabine (GEM) in patients with resected pancreatic cancer. METHODS: Patients
      with invasive ductal pancreatic cancer who underwent radical surgery were
      enrolled and assigned to receive uracil/tegafur (UFT) and GEM together (GU) or
      GEM alone (G). GEM was administrated at a dosage of 1 g/m(2) intravenously weekly
      3 of 4 weeks and UFT at a dosage of 200 mg/day orally continuously. Eligibility
      included resection status 0 or 1, and no previous chemo- or/and radiation
      therapy. The primary endpoint was disease-free survival (DFS), and secondary
      endpoints included overall survival (OS) and toxicity. RESULTS: Between 2002 and
      2005, 100 patients were randomized into the 2 arms of the trial (50 patients to
      GU and 50 to G). One patient in the G group was found to be ineligible. Baseline
      characteristics were well balanced between the 2 groups. With a median
      observation period of 21 months, the 1- and 3-year DFS rates were 50.0% and 17.7%
      in the GU group and 49.0% and 21.6% in the G group, respectively. The median OS
      was 21.2 months in the GU group and 29.8 months in the G group. Toxicity was
      minor and acceptable, less than grade 4 in both groups. CONCLUSIONS:
      Postoperative GEM-based adjuvant chemotherapy was safe and well tolerated.
      However, addition of UFT with GEM did not improve DFS as compared with GEM alone.
      Further clinical trial resources for adjuvant chemotherapy should address other
      combinations and novel agents.

PMID- 18823025
TI  - Genetic variations in cell-cycle pathway and the risk of oral premalignant
      lesions.
AB  - BACKGROUND: Cell-cycle checkpoint controls regulate cell-cycle progression and
      proliferation. Alterations in cell-cycle control mechanisms are linked to
      tumorigenesis. METHODS: This case-control study included 147 cases and 147
      controls. The authors used a pathway-based approach to assess the association
      between 10 potential functional single-nucleotide polymorphisms from 7 cell-cycle
      control genes and the risk of oral premalignant lesions (OPLs). They also used
      classification and regression tree analysis to examine high-order gene-gene and
      gene-smoking interactions. RESULTS: Compared with the homozygous wild-type GG
      genotype of CCND1 P241P, individuals with the AG genotype exhibited an increased
      risk of OPL (odds ratio, 1.58; 95% confidence interval, 0.89-2.83), and carriers
      of the AA genotype had a significantly increased risk of OPL (odds ratio, 2.75;
      95% confidence interval, 1.33-5.71), with risk increasing significantly with the
      increasing number of variant alleles (P= .006). The risk of OPL increased
      significantly as the number of unfavorable genotypes in the pathway increased (P=
      .002). The final decision tree in the classification and regression tree analysis
      contained 5 terminal nodes. Compared with the never smokers (the lowest risk
      group), the odds ratios for terminal nodes 2 through 5 ranged from 1.21 to 5.40.
      CONCLUSIONS: The results illustrated the advantage of using a pathway-based
      approach for analyzing gene-gene and gene-smoking interactions. Specifically, the
      authors showed that genetic polymorphisms in cell-cycle control pathway genes may
      contribute to the risk of OPL.

PMID- 18823026
TI  - Hemimasticatory spasm with lateral jaw deviations.

PMID- 18823027
TI  - Pisa syndrome and parkinsonism secondary to valproic acid in Huntington's
      disease.

PMID- 18823028
TI  - Pathogenesis of PD: missing the point.

PMID- 18823029
TI  - Antitumor effect of adriamycin-encapsulated nanoparticles of poly(DL-lactide-co
      glycolide)-grafted dextran.
AB  - In this study, we prepared adriamycin (ADR)-encapsulated core-shell type
      nanoparticles of a poly(DL-lactide-co-glycolide) (PLGA) grafted-dextran (DexLG)
      copolymer and evaluated its antitumor activity in vitro and in vivo. The particle
      size of ADR-encapsulated DexLG nanoparticles was around 50-200 nm and the
      morphology was spherical shapes at transmission electron microscopy (TEM)
      observation. Since reconstitution of lyophilized nanoparticles is essential to
      practical use in vivo, ADR-encapsulated DexLG nanoparticles were lyophilized and
      reconstituted them into deionized water. Although reconstitution process caused
      increase of particle size, drug release behavior of nanoparticles was not
      significantly changed before and after reconstitution process. The ADR
      encapsulated DexLG nanoparticles were less cytotoxic than free ADR plus empty
      nanoparticles at in vitro, while empty DexLG nanoparticles did not significantly
      affect cell viability. Even if free ADR plus empty nanoparticles are most
      effective to inhibit tumor growth at tumor-induced animal model using CT-26
      cells, ADR-encapsulated DexLG nanoparticles showed increased survivability of
      mice. These results indicated that ADR-encapsulated DexLG nanoparticles are
      promising vehicles for antitumor drug delivery.

PMID- 18823030
TI  - Second solid malignancies among children, adolescents, and young adults diagnosed
      with malignant bone tumors after 1976: follow-up of a Children's Oncology Group
      cohort.
AB  - BACKGROUND: The growing number of individuals surviving childhood cancer has
      increased the awareness of adverse long-term sequelae. One of the most worrisome
      complications after cancer therapy is the development of second malignant
      neoplasms (SMNs). METHODS: The authors describe the incidence of solid organ SMN
      in survivors of pediatric malignant bone tumors who were treated on legacy
      Children's Cancer Group/Pediatric Oncology Group protocols from 1976 to 2005.
      This retrospective cohort study included 2842 patients: 1686 who were treated for
      osteosarcoma (OS) and 1156 who were treated for Ewing sarcoma (ES). RESULTS: The
      cohort included 56% boys/young men and 44% girls/young women, and the median age
      at primary diagnosis was 13 years. The median length of follow-up was 6.1 years
      (range, 0-20.9 years). In this analysis, 64% of patients were alive. Seventeen
      patients with solid organ SMN were identified. The standardized incidence ratio
      was 2.9 (95% confidence interval [CI], 1.4-5.4) for patients who were treated for
      OS and 5.0 (95% CI, 2.6-9.4) for patients who were treated for ES. The median
      time from diagnosis to development of solid SMN was 7 years (range, 1-13 years).
      The 10-year cumulative incidence of solid organ SMN for the entire cohort was
      1.4% (95%CI 0.6%-2%). CONCLUSIONS: The magnitude of risk of solid SMNs was modest
      after treatment for malignant bone tumors. However, radiation-related solid SMNs
      will increase with longer follow-up. Because nearly 33% of patients die from
      their disease, recurrence remains the most significant problem. The development
      of improved therapies with fewer long-term consequences is paramount. Follow-up
      should focus on monitoring for both recurrence of primary malignancies and
      development of SMNs.

PMID- 18823031
TI  - Protein aggregation: pathways, induction factors and analysis.
AB  - Control and analysis of protein aggregation is an increasing challenge to
      pharmaceutical research and development. Due to the nature of protein
      interactions, protein aggregation may occur at various points throughout the
      lifetime of a protein and may be of different quantity and quality such as size,
      shape, morphology. It is therefore important to understand the interactions,
      causes and analyses of such aggregates in order to control protein aggregation to
      enable successful products. This review gives a short outline of currently
      discussed pathways and induction methods for protein aggregation and describes
      currently employed set of analytical techniques and emerging technologies for
      aggregate detection, characterization and quantification. A major challenge for
      the analysis of protein aggregates is that no single analytical method exists to
      cover the entire size range or type of aggregates which may appear. Each
      analytical method not only shows its specific advantages but also has its
      limitations. The limits of detection and the possibility of creating artifacts
      through sample preparation by inducing or destroying aggregates need to be
      considered with each method used. Therefore, it may also be advisable to
      carefully compare analytical results of orthogonal methods for similar size
      ranges to evaluate method performance.

PMID- 18823032
TI  - Release mechanisms of a sparingly water-soluble drug from controlled porosity
      osmotic pump pellets using sulfobutylether-beta-cyclodextrin as both a
      solubilizing and osmotic agent.
AB  - The purpose of this work is to delineate the release mechanisms of a sparingly
      water-soluble drug, prednisolone (PDL), from a microporous or controlled porosity
      osmotic pump pellet (CP-OPP) using sulfobutylether-beta-cyclodextrin (CD) as both
      a solubilizing and osmotic agent. All factors, osmotic and diffusional,
      influencing drug release as described by the Theeuwes and Zentner equation were
      partially demonstrated in an earlier paper1 and are further quantitatively
      evaluated here to determine whether the equation may be applied to CP-OPPs. The
      PDL release rate from the CP-OPPs containing precomplexed PDL follows the zero
      order kinetics for up to 30-40% of drug release during the first 1-2 h and
      subsequently nonzero order kinetics. The zero-order drug release phase reveals
      the main contribution is from osmotic pumping with a negligible diffusion
      component, resulting from the nearly constant driving forces in the system. The
      nonzero order drug release phase is associated with the dynamic changes in the
      system (e.g., declining osmotic driving force and greater diffusion component
      with time). In addition, the parameters related to membrane characteristics were
      determined, and the effect of viscosity was evaluated for the pellet system. The
      membranes coated on the CP-OPPs are less permeable to water or solutes than the
      membranes coated on the previously reported tablets. The viscosity due to the CD
      decreases as a function of CD concentration, which partly affects the observed
      drug release profiles. The viscosity effect of CD is significant and captured in
      a hydraulic permeability term.

PMID- 18823033
TI  - Short-term effects of treatment-induced hormonal changes on cognitive function in
      breast cancer patients: results of a multicenter, prospective, longitudinal
      study.
AB  - BACKGROUND: It is suspected that estrogen depletion resulting from treatment may
      contribute to cognitive compromise in patients with breast cancer. However, the
      evidence for estrogen effects on cognition is inconclusive, and the consequences
      of hormonal changes for cognitive function in patients with cancer rarely have
      been investigated. In this study, the authors investigated the effects of
      treatment-induced menopause and antiestrogen therapy with tamoxifen and aromatase
      inhibitors (AIs) on cognitive function. METHODS: Cognitive performance was
      assessed in 101 patients with breast cancer before the start of cancer therapy
      (T1), toward the end of neoadjuvant chemotherapy (T2), and 1 year after baseline
      (T3) using 12 cognitive tests. Menopause occurred in a subgroup of patients, and
      an overlapping subgroup started antiestrogen therapy with tamoxifen or AIs.
      Linear mixed-effects models that made it possible to determine effects at group
      levels and individual levels simultaneously were used for statistical analysis.
      RESULTS: At the group level, a significant favorable effect of induced menopause
      emerged in a test of executive function (P= .0035). Two additional group-level
      effects of induced menopause, both favorable, and 2 individual-level effects that
      were positive in some patients and negative in others were not significant when
      multiple testing was taken into account. No significant effects of tamoxifen or
      AIs on cognitive function were observed. CONCLUSIONS: Hormonal changes did not
      appear to contribute to cognitive compromise in patients with breast cancer
      during the first year after diagnosis. Antiestrogen treatment with tamoxifen or
      AIs did not affect cognition, and the effects of induced menopause were more
      likely to be favorable. However, the possibility that some cognitive decline
      occurs in individual patients could not be excluded.

PMID- 18823034
TI  - Cancer-specific survival outcomes among patients treated during the cytokine era
      of kidney cancer (1989-2005): a benchmark for emerging targeted cancer therapies.
AB  - BACKGROUND: The management of renal cell carcinoma (RCC) is evolving toward less
      extirpative surgery and the use of targeted therapy. The authors set out to
      provide a benchmark against which emerging therapies should be measured. METHODS:
      A prospective database including clinical and pathological variables for 1632
      patients with RCC treated between 1989 and 2005 was queried. Patients were
      stratified using the University of California-Los Angeles Integrated Staging
      System (UISS) into low-, intermediate-, and high-risk groups. Disease-specific
      survival (DSS) was measured. Response to systemic therapy for patients with
      advanced disease was assessed. RESULTS: Nephrectomy was performed in 1492
      patients. Overall 5-, 10-, and 15-year DSS was 55%, 40%, and 29%. For localized
      disease, 5- and 10-year DSS for UISS low-, intermediate-, and high-risk groups
      was 97% and 92%, 81% and 61%, and 62% and 41%, respectively. For metastatic
      disease, 5- and 10-year DSS for UISS low-, intermediate-, and high-risk groups
      was 41% and 31%, 18% and 7%, and 8% and 0%, respectively. Patients with
      metastatic disease receiving immunotherapy (n=453) had complete response in 7%
      (median survival [MS], 120+ months), partial response in 15% (MS, 42.8 months),
      stable disease in 33% (MS, 38.6 months), and progressive disease in 45% (MS, 11.6
      months). CONCLUSIONS: Most patients with localized RCC do well with surgery
      alone, but effective adjuvant therapy is needed for patients identified as at
      high risk for recurrence. For advanced disease, newer targeted and potentially
      less toxic treatments should be at least as effective as those achieved with
      aggressive surgical resection and immunotherapy.

PMID- 18823035
TI  - Neoadjuvant gemcitabine and cisplatin: another step on the path toward improving
      the outcomes of patients with high-risk, invasive bladder cancer.

PMID- 18823037
TI  - Levodopa affects functional brain networks in Parkinsonian resting tremor.
AB  - Resting tremor in idiopathic Parkinson's disease (PD) is associated with an
      oscillatory network comprising cortical as well as subcortical brain areas. To
      shed light on the effect of levodopa on these network interactions, we
      investigated 10 patients with tremor-dominant PD and reanalyzed data in 11
      healthy volunteers mimicking PD resting tremor. To this end, we recorded surface
      electromyograms of forearm muscles and neuromagnetic activity using a 122-channel
      whole-head magnetometer (MEG). Measurements were performed after overnight
      withdrawal of levodopa (OFF) and 30 min after oral application of fast-acting
      levodopa (ON). During OFF, patients showed the typical antagonistic resting
      tremor. Using the analysis tool Dynamic Imaging of Coherent Sources, we
      identified the oscillatory network associated with tremor comprising
      contralateral primary sensorimotor cortex (S1/M1), supplementary motor area
      (SMA), contralateral premotor cortex (PMC), thalamus, secondary somatosensory
      cortex (S2), posterior parietal cortex (PPC), and ipsilateral cerebellum
      oscillating at 8 to 10 Hz. After intake of levodopa, we found a significant
      decrease of cerebro-cerebral coupling between thalamus and motor cortical areas.
      Similarly, in healthy controls mimicking resting tremor, we found a significant
      decrease of functional interaction within a thalamus-premotor-motor network
      during rest. However, in patients with PD, decrease of functional interaction
      between thalamus and PMC was significantly stronger when compared with healthy
      controls. These data support the hypothesis that (1) in patients with PD the
      basal ganglia and motor cortical structures become more closely entrained and (2)
      levodopa is associated with normalization of the functional interaction between
      thalamus and motor cortical areas.

PMID- 18823038
TI  - Parkinsonism in polycythaemia vera probably due to manganism.

PMID- 18823036
TI  - A role for neoadjuvant gemcitabine plus cisplatin in muscle-invasive urothelial
      carcinoma of the bladder: a retrospective experience.
AB  - BACKGROUND: Neoadjuvant cisplatin-based chemotherapy improves survival in muscle
      invasive urothelial cancer, with MVAC (methotrexate, vinblastine, doxorubicin and
      cisplatin) considered the standard regimen. Gemcitabine plus cisplatin (GC) has
      similar efficacy and less toxicity than MVAC in metastatic disease, but is
      untested as neoadjuvant treatment. METHODS: The authors retrospectively evaluated
      patients with muscle-invasive urothelial carcinoma who received neoadjuvant GC
      before radical cystectomy between November 2000 and December 2006 at Memorial
      Sloan-Kettering Cancer Center. Post-therapy pathological downstaging to either
      residual disease at cystectomy (pT0) or no residual muscle-invasion (<pT2, ie,
      pT0, pTIS, pT1), chemotherapy delivery, and disease-free survival were the
      endpoints of interest. For comparison, similar endpoints were assessed in a
      historical cohort treated with neoadjuvant MVAC. RESULTS: Four cycles of
      neoadjuvant GC were given over 12 weeks (n=42). Thirty-nine (93%) of 42 patients
      received 4 cycles, with a median 91% drug delivery for cisplatin and 90% for
      gemcitabine. The pT0 proportion was 26% (95% confidence interval [CI], 14-42),
      and no residual muscle-invasive disease proportion (<pT2) was 36% (95% CI, 21
      52); pT0 was achieved in 28% (95% CI, 16-42) and <pT2 in 35% (95% CI, 23-49) of
      54 MVAC-treated patients. All 15 GC patients achieving <pT2 pathologic stage
      remained disease-free at a median follow-up of 30 months. CONCLUSIONS:
      Neoadjuvant GC is feasible and allows for timely drug delivery. The proportion of
      GC-treated patients whose primary tumors were downstaged, with prolonged disease
      free survival and minimal or no residual disease, was similar to MVAC-treated
      patients.

PMID- 18823039
TI  - Effects of dopaminergic medications on psychosis and motor function in dementia
      with Lewy bodies.
AB  - Dopaminergic treatment in dementia with Lewy bodies (DLB) requires balancing risk
      of worsened psychosis and potential motor benefit. We assessed the effects of
      increased dopaminergic medication on psychosis and motor function in DLB. We
      studied 19 subjects fulfilling probable DLB Consensus criteria before and after
      increased dopaminergic medications. Standard clinical measures included: Thought
      Disorder score from the Unified Parkinson's disease Rating Scale (UPDRS) Part I,
      total motor score (UPDRS Part III), and Hoehn-Yahr (H&Y) stage. Motor benefit
      defined as >10% improvement over baseline UPDRS Part III score, occurred in only
      one-third of subjects. In this group, worsened hallucinations or psychosis
      developed in one-third. Considering motor benefit without exacerbation of
      psychosis as our aim, only 4 DLB subjects (22%) achieved this goal. Our results
      suggest that dopaminergic medications have limited benefit in DLB because of the
      low likelihood of motor improvement and the risk of psychosis exacerbation.

PMID- 18823040
TI  - Normal dopamine transporter single photon-emission CT scan in corticobasal
      degeneration.

PMID- 18823041
TI  - An updated catalog of prostate cancer predictive tools.
AB  - Accurate estimates of risk are essential for physicians if they are to recommend
      a specific management to patients with prostate cancer. Accurate risk estimates
      also are required for clinical trial design to ensure that homogeneous, high-risk
      patient groups are used to investigate new cancer therapeutics. Using the MEDLINE
      database, a literature search was performed on prostate cancer predictive tools
      from January 1966 to July 2007. The authors recorded input variables, the
      prediction form, the number of patients used to develop prediction tools, the
      outcome being predicted, prediction tool-specific features, predictive accuracy,
      and whether validation was performed. Each prediction tool was classified into
      patient clinical disease state and the outcome being predicted. First, the
      authors described the criteria for evaluation (predictive accuracy, calibration,
      generalizability, head-to-head comparison, and level of complexity) and the
      limitations of current predictive tools. The literature search generated 109
      published prediction tools, including only 68 that had undergone validation. An
      increasing number of predictive tools addressed important endpoints, such as
      disease recurrence, metastasis, and survival. Despite their limitations and the
      limitations of data, predictive tools are essential for individualized, evidence
      based medical decision making. Moreover, the authors recommend wider adoption of
      risk-prediction models in the design and implementation of clinical trials. Among
      prediction tools, nomograms provide superior, individualized, disease-related
      risk estimations that facilitate management-related decisions. Nevertheless, many
      more predictive tools, comparisons between them, and improvements to existing
      tools are needed.

PMID- 18823042
TI  - Desmoplastic neurotropic melanoma: a clinicopathologic analysis of 128 cases.
AB  - BACKGROUND: Several studies have suggested that desmoplastic neurotropic melanoma
      (DNM) is associated with higher local recurrence rates than other types of
      melanoma. The authors investigated the local recurrence rates for patients with
      DNM after surgery alone or surgery followed by radiotherapy (RT). METHODS: One
      hundred twenty-eight patients with DNM were treated at the Sydney Melanoma Unit
      and the Sydney Cancer Center from 1996 to 2007. All patients underwent local
      excision, 27 patients also received RT. For both groups, clinical and pathologic
      features, treatment details, and local recurrence data were analyzed. RESULTS:
      The median age at diagnosis was 65.5 years. The ratio of men to women was 2.7:1.
      The head and neck was the most common location (51%). The median Breslow
      thickness was 4 mm, and 99% of patients had Clark Level IV or V primary tumors.
      Patients who received adjuvant RT had thicker tumors (P = .003), deeper Clark
      level invasion (P < .001), and narrower excision margins (P < .001). There were 8
      local recurrences, including 6 (6%) in the surgery only group and 2 (7%) in the
      adjuvant RT group. A positive margin (P < .001) and head and neck location (P =
      .03) were significant predictors of local recurrence. CONCLUSIONS: The local
      recurrence rate in this series was lower than the rates reported in historic
      control groups and in the authors' previous temporal cohort. The results
      indicated that clear surgical margins are of paramount importance in minimizing
      local recurrence; when margins are compromised, the addition of RT may reduce
      local recurrence rates compared with historic controls. A prospective randomized
      trial is needed to quantify the risk reduction with adjuvant RT.

PMID- 18823043
TI  - Risk of radiation-related salivary gland carcinomas among survivors of Hodgkin
      lymphoma: a population-based analysis.
AB  - BACKGROUND: Radiotherapy for Hodgkin lymphoma (HL) increases the risk of salivary
      gland carcinomas (SGC). To the authors' knowledge, however, the magnitude of the
      risk has not been assessed to date. METHODS: The risks of SGC among 20,928 1-year
      survivors of HL who were diagnosed between 1973 and 2003 were evaluated in 11
      population-based cancer registry areas of the Surveillance, Epidemiology, and End
      Results (SEER) program. Observed-to-expected ratios (O/E) were assessed by
      radiation treatment, sex, age at the time of HL diagnosis, calendar year of
      diagnosis, attained age, time since HL diagnosis, histologic type of SGC, and
      site of occurrence in the major salivary glands. RESULTS: Among 11,047 HL
      patients who received radiotherapy as part of their initial treatment for HL, 21
      developed subsequent invasive SGC (O/E = 16.9; 95% confidence interval [95% CI],
      10.4-25.8). The risk of radiation-related SGC was highest for younger HL patients
      (age <20 years) (O/E = 45.5; 95% CI, 12.4-116.5) and among 10-year survivors (O/E
      = 23.9; 95% CI, 13.1-40.1), with risks remaining elevated for at least 2 decades
      after irradiation. Significant differences in risk by histologic type were
      observed, with a particularly high risk of developing mucoepidermoid carcinomas
      (O = 14; O/E = 44.2 [95% CI, 24.2-74.2]) and adenocarcinomas (O = 4; O/E = 30.6
      [95% CI, 8.3-78.2]) noted. CONCLUSIONS: HL patients treated with radiotherapy
      experienced a significantly increased risk of SGC, particularly when exposed at
      young ages or for at least 2 decades after exposure. Although the results of the
      current study reflect the late effects of former HL treatment approaches, they
      point to the importance of long-term follow-up and a heightened awareness of SGC
      risk in this population.

PMID- 18823044
TI  - Clinical and genetic characterization of a large Dutch family with primary focal
      dystonia.
AB  - We describe a large family with a primary focal dystonia from a small Dutch
      village on a former island. Twenty-four individuals spanning three generations
      were examined by two movement-disorder neurologists. Two other movement-disorder
      neurologists evaluated the videos independently. Subjects were classified as
      "affected," "possibly affected," or "not affected." A diagnosis was defined if
      all the neurologists agreed on the definition. Eight definitely affected and four
      possibly affected subjects were detected. Clinical presentation consisted of mild
      cranio-cervical-brachial dystonia. Mean age at onset was 45.5 years (range, 39
      56). Mean BFMDRS motor score was 4.4 (range, 1-8). Mean TWSTRS score (part I) was
      11.3 (range, 8-23). Mutations in DYT1 gene and in the epsilon-sarcoglycan (SGCE)
      genes were not detected. We could not find linkage to the dominant DYT6, DYT7,
      DYT13, or the recessive DYT16 loci. The identification and accurate clinical
      evaluation of large dystonia families not linked to known genes is crucial for
      further advancement in molecular genetic characterization of focal dystonia.

PMID- 18823045
TI  - Molecular and functional characteristics of proton-coupled folate transporter.
AB  - Proton-coupled folate transporter (PCFT) has recently been identified as the
      molecular entity of the carrier-mediated intestinal folate transport system. PCFT
      has been demonstrated to be most abundantly expressed in the upper small
      intestine, localizing at the brush border membrane of epithelial cells, transport
      folate and its analogs more efficiently at lower (acidic) pH by a H(+)-coupled
      cotransport mechanism, and have a high affinity for folate with a Michaelis
      constant (K(m)) of a few microM at pH 5.5 and somewhat lower affinities for
      reduced folates and methotrexate (MTX). A loss of PCFT function due to a
      homozygous mutation in its gene has been indicated to be responsible for
      hereditary folate malabsorption. Thus, PCFT has all the characteristics of the
      brush border H(+)-coupled cotransporter for folate and analogs, which has long
      been suggested to be present in the intestine. Furthermore, sulfasalazine was
      found to be a potent inhibitor of PCFT, suggesting that it is a risk factor that
      would cause malabsorption of folate and also MTX, when coadministered in the
      treatment of rheumatoid arthritis. Understanding the molecular and functional
      characteristics of PCFT should be important and helpful in exploring therapeutic
      strategies for folate malabsorption and in optimizing therapies using antifolate
      drugs.

PMID- 18823046
TI  - Monitoring intracellular labile iron pools: A novel fluorescent iron(III) sensor
      as a potential non-invasive diagnosis tool.
AB  - The physiological and pathophysiological importance of intracellular redox active
      "labile" iron has created a significant need for improved noninvasive diagnostic
      tools to reliably monitor iron metabolism in living cells. In this context,
      fluorescent iron-sensitive chemosensors in combination with digital fluorescence
      spectroscopic methods have proven to be highly sensitive and indispensable tools
      to determine cellular iron homeostasis. Recently, application of fluorescent iron
      sensors has led to the identification of a complex sub-cellular iron
      compartmentation. Cell organelle-specific iron sensors will significantly
      contribute to enhance fundamental knowledge of cellular iron trafficking,
      representing a crucial prerequisite for the future development of therapeutic
      strategies in iron dysregulatory diseases. Here we present physicochemical
      characterization and functional investigation of a new 3-hydroxypyridin-4-one
      based fluorescent iron(III) sensor, exclusively monitoring labile iron pools in
      the endosomal/lysosomal compartments. In vitro studies of the fluorescein labeled
      probe were carried out in murine bone marrow derived macrophages.
      Endosomal/lysosomal accumulation of the probe was revealed by confocal
      microscopy. Flow cytometry analyses demonstrated high sensitivity of the probe
      towards exogenous alterations of intracellular iron concentrations as well as in
      response to the chelation potency of iron chelators, clinically approved for
      treatment of iron-overload related diseases.

PMID- 18823047
TI  - Essential tremor might be less frequent than Parkinson's disease in North Israel
      Arab villages.
AB  - Essential tremor (ET) is much more prevalent than Parkinson's disease (PD) in
      Western countries. We estimated ET and PD prevalence in Wadi Ara Arabic villages
      in Northern Israel. In this door-to-door survey, all consenting residents aged
      >or=65 years were systematically examined by an Arabic speaking team. No
      prescreening questionnaires were used. A random sample of 900 subjects [437
      males, mean age (SD) = 72.6 years (6.6)] of the 2,163 eligible residents were
      evaluated. Sixteen subjects had an action, intentional tremor. Tremor prevalence
      was estimated as 1.78% (95% CI 1.1-2.87). Nine of these had another likely cause
      of tremor. Only 7 patients were diagnosed as ET [prevalence 0.78% (95% CI 0.38
      1.6)]. PD was diagnosed in 13 subjects. PD prevalence was 1.44% (95% CI 0.84
      2.45). ET is unusually uncommon in this population and possibly even less
      frequent than PD. The PD prevalence in Wadi Ara is similar to that reported in
      Western countries.

PMID- 18823048
TI  - Structural findings in the basal ganglia in genetically determined and idiopathic
      Parkinson's disease.
AB  - A bilateral compensatory increase of basal ganglia (BG) gray matter value (GMV)
      was recently demonstrated in asymptomatic Parkin mutation carriers, who likely
      have an increased risk to develop Parkinson's disease (PD). We hypothesized BG
      morphological changes in symptomatic Parkin mutation carriers (sPARKIN-MC) and
      idiopathic PD patients (iPD) after the occurrence of PD symptoms, reflecting the
      breakdown of compensatory mechanisms. Nine sPARKIN-MC, 14 iPD, and 24 controls
      were studied clinically and with voxel-based morphometry. Analysis of variance
      revealed mainly BG decrease of GMV in sPARKIN-MC and to a lesser extent in iPD.
      However, a slight increase in GMV was also found in the right globus pallidus
      externus in sPARKIN-MC and in the right putamen in iPD. This may reflect a
      structural correlate of functional compensation that can only partially be
      maintained when nigrostriatal neurodegeneration becomes manifest. Simple
      regression analyses with the UPDRS-III and disease duration score revealed a
      distinct more bilateral linear decrease of BG GMV in sPARKIN-MC than in iPD that
      may correspond to previous findings showing a symmetric reduction in putaminal
      (18)F-DOPA-uptake and bilateral manifestation of symptoms in sPARKIN-MC. In
      symptomatic PD, BG are subject to a progressive atrophy, which gradually
      increases with disease severity and duration.

PMID- 18823049
TI  - Effect of thalamotomy on focal hand dystonia in a family with DYT1 mutation.
AB  - We report the clinical and molecular features of a family with focal hand
      dystonia caused by DYT1 mutation. Four members of a family who underwent
      thalamotomy showed a marked and sustained therapeutic benefit that lasted for up
      to 12 years without recurrence of dystonia or any significant surgical
      complication. The hand dystonia caused by DYT1 mutation may be successfully
      managed by thalamotomy.

PMID- 18823050
TI  - Cell cycle progression in Escherichia coli B/r affects transcription of certain
      genes: Implications for synthetic genome design.
AB  - We propose that transcript levels for some genes are affected by the bacterial
      cell division cycle and this may be an important factor to consider when
      designing synthetic bacterial genomes. To test this hypothesis, transcript levels
      of 58 genes in Escherichia coli B/r A were determined at five times during the
      cell division cycle. A two-step ANOVA technique was used to analyze data from
      custom oligonucleotide microarrays containing genes involved in important
      cellular processes including central metabolism, macromolecular synthesis, and
      transport and secretion. Consistent with results previously found in Caulobacter,
      approximately 17% of the transcript levels were cell cycle dependent. Cell cycle
      regulation can be divided into two classes: genes displaying increased transcript
      concentrations following gene replication and genes displaying an increased
      transcript concentration prior to replication initiation. Transcripts levels for
      hns, uspA, and zwf were affected by the cell division cycle, but did not fit well
      into either class. These results indicate that transcription of a significant
      fraction of the genome is affected by replication cycle progression. The results
      also show that both physical gene position and the physiological function of a
      gene affect when it is transcribed. In addition to the simple association with
      replication fork progression, other phenomena must be occurring to account for
      some of our observations. In conclusion, gene position, with regard to the C
      period, and gene function are important factors to incorporate into design
      criteria for synthetic bacterial genomes.

PMID- 18823051
TI  - Hydrogen photoproduction by nutrient-deprived Chlamydomonas reinhardtii cells
      immobilized within thin alginate films under aerobic and anaerobic conditions.
AB  - A new technique for immobilizing H2-photoproducing green algae within a thin
      (<400 microm) alginate film has been developed. Alginate films with entrapped
      sulfur/phosphorus-deprived Chlamydomonas reinhardtii, strain cc124, cells
      demonstrate (a) higher cell density (up to 2,000 microg Chl mL(-1) of matrix),
      (b) kinetics of H2 photoproduction similar to sulfur-deprived suspension
      cultures, (c) higher specific rates (up to 12.5 micromol mg(-1) Chl h(-1)) of H2
      evolution, (d) light conversion efficiencies to H2 of over 1% and (e)
      unexpectedly high resistance of the H2-photoproducing system to inactivation by
      atmospheric O2. The algal cells, entrapped in alginate and then placed in vials
      containing 21% O2 in the headspace, evolved up to 67% of the H2 gas produced
      under anaerobic conditions. The results indicate that the lower susceptibility of
      the immobilized algal H2-producing system to inactivation by O2 depends on two
      factors: (a) the presence of acetate in the medium, which supports higher rates
      of respiration and (b) the capability of the alginate polymer itself to
      effectively separate the entrapped cells from O2 in the liquid and headspace and
      restrict O2 diffusion into the matrix. The strategy presented for immobilizing
      algal cells within thin polymeric matrices shows the potential for scale-up and
      possible future applications.

PMID- 18823052
TI  - Culture nutrition and physiology impact the inhibitor tolerance of the yeast
      Pichia stipitis NRRL Y-7124.
AB  - Pichia stipitis NRRL Y-7124 is one of the natural yeasts best able to utilize
      biomass because it is able to ferment hexoses and the pentose, xylose, to
      economically recoverable concentrations of ethanol. To test the impact of culture
      conditions on inhibitor tolerance, inhibitors were spiked to growing or
      stationary-phase P. stipitis supplied either glucose or xylose and varying
      nitrogen and mineral compositions; then the ensuing specific death rate response
      was measured. Resistance of glucose- or xylose-grown cells to inhibitors was
      generally greater in stationary-phase cells than log-phase cells, despite a
      greater exposure of stationary cells to ethanol. Consistent with this, the
      specific productivity of detoxification products, furan methanol or furan-2,5
      dimethanol, from respective spikes of furfural or HMF increased as cultures
      progressed into stationary phase. However, when xylose was the substrate, ethanol
      resistance behaved uniquely and was greater for log- than stationary-phase cells.
      Amino acid enrichment of the growth medium significantly enhanced ethanol
      tolerance if xylose was the carbon source, but had no impact if glucose supplied
      carbon. Regardless of the carbon source, amino acid enrichment of the culture
      medium enhanced the ability of cells to resist furfural and HMF exposure. Mineral
      compositions tested had little impact on inhibitor resistance except stationary
      phase xylose-grown cells were more susceptible to inhibitor exposure when
      magnesium sulfate was excessive. Observed tolerance optimization based on
      specific death rate as a function of culture physiological state, carbon source,
      nitrogen source and mineral composition provides new knowledge supporting process
      designs to convert biomass to ethanol using P. stipitis.

PMID- 18823053
TI  - Phase 2 study of gemcitabine and irinotecan in metastatic breast cancer with
      correlatives to determine topoisomerase I localization as a predictor of
      response.
AB  - BACKGROUND: Gemcitabine incorporation into DNA enhances cleavage complexes in
      vitro when combined with topoisomerase I inhibitors and demonstrates synergy in
      cancer cells when given with irinotecan. Topoisomerase I inhibitors require that
      topoisomerase I interacts with DNA to exert activity. METHODS: Patients who had
      received previous anthracycline therapy or were not candidates for anthracycline
      therapy received gemcitabine at a dose of 1000 mg/m2 intravenously over 30
      minutes followed by irinotecan at a dose of 100 mg/m2 over 90 minutes on Days 1
      and 8 of a 21-day cycle. The primary endpoint was improvement in response from
      that historically observed with gemcitabine (from 25% to 45%) as measured by
      Response Evaluation Criteria in Solid Tumors. Correlative studies included
      characterization of cellular levels and nuclear distribution of topoisomerase I
      and pharmacokinetic analysis of gemcitabine and irinotecan. RESULTS: Forty-nine
      patients were assessed for response. The response rate was approximately 25% (all
      partial responses [PRs], 12 patients; 95% confidence interval [95% CI], 13-39).
      Six patients had stable disease (SD) for > or =6 months for a clinical benefit
      rate (PR + SD) of 39%. The median time to disease progression was 3.7 months (95%
      CI, 2.5 months-4.6 months), and median survival was 11.6 months (95% CI, 8.9
      months-15 months). Toxicities included neutropenia, nausea, and vomiting. Seven
      of 9 tissue biopsies were assessable for topoisomerase I. Tumors with the 2
      lowest nuclear to cytoplasmic ratios demonstrated no response to irinotecan.
      CONCLUSIONS: Gemcitabine and irinotecan are active in metastatic breast cancer,
      but response did not meet predetermined response parameters, and the null
      hypothesis was accepted. Topoisomerase I localization can be measured in
      metastatic breast cancer. Further validation is needed to determine whether this
      assay can predict response.

PMID- 18823054
TI  - Phase 1 trial of lipoplatin and gemcitabine as a second-line chemotherapy in
      patients with nonsmall cell lung carcinoma.
AB  - BACKGROUND: : Lipoplatin is a new liposomal cisplatin that already has been
      tested in solid tumors, with encouraging results. The purpose of the current
      study was to determine the maximum tolerated dose (MTD) and the dose-limiting
      toxicity (DLT) of a 21-day regimen of lipoplatin plus a fixed dose of gemcitabine
      in patients with refractory or resistant nonsmall cell lung carcinoma (NSCLC)
      with an Eastern Cooperative Oncology Group (ECOG) performance status of </=2.
      METHODS: : The lipoplatin dose was escalated at 100 mg/m(2) by increments of 10
      mg/m(2) on Days 1 and 8, with gemcitabine at a dose of 1000 mg/m(2) administered
      on Days 1 and 8, repeated every 21 days. Hematopoietic growth factors were not
      allowed. Thirteen patients with advanced stage NSCLC who had been pretreated with
      platinum combination chemotherapy were enrolled in this phase 1 trial. At least 3
      patients were entered at each dose level. RESULTS: : At the fourth dose level,
      the DLT was reached (grade 3 neutropenia [according to World Health Organization
      criteria] in 3 of 4 patients 75%]; the fourth patient demonstrated degradation of
      performance status). Therefore, the third dose level (lipoplatin at a dose of 120
      mg/m(2)) was defined as the MTD. At the same dose level, 2 of 4 patients had
      grade 3 thrombocytopenia. At the fourth dose level, 1 patient achieved a partial
      response and 1 patient had stable disease. Another patient achieved stable
      disease at the second dose level. Therefore, the overall disease control rate was
      23% (3 of 13 patients). The median overall survival was 29 weeks (range, 4 weeks
      59 weeks) and the median time to disease progression was 12 weeks (range, 3 weeks
      36 weeks). CONCLUSIONS: : The pharmacokinetic profile of the 2 compounds used in
      the current study are not modified when they are administered according to the
      schedule evaluated in this trial. When one considers that the patients in the
      current study had refractory or resistant NSCLC, the authors concluded that the
      combination of lipoplatin administered at a dose of 120 mg/m(2) and gemcitabine
      administered at a dose of 1000 mg/m(2) on Days 1 and 8 every 3 weeks needs to be
      studied further in phase 2 trials. Cancer 2008. (c) 2008 American Cancer Society.

PMID- 18823055
TI  - A modular "toolbox" approach to flexible branched multimacrocyclic hosts as
      precursors for multiply interlocked architectures.
AB  - Tetralactam macrocycles can be functionalized by a variety of cross-coupling
      reactions. A modular "toolbox" strategy is presented that allows 1) several
      tetralactam macrocycles to be covalently connected with each other or with a
      central spacer, 2) the macrocycles to be substituted with or connected to
      different chromophores, and 3) metal-coordination sites to be attached to the
      macrocycles. With this approach a series of different oligo-macrocyclic hosts was
      obtained with great structural diversity and enormous potential for further
      functionalization. Rotaxanes made on the basis of these macrocycles have been
      synthesized to demonstrate their utility in building more complex supramolecular
      architectures.

PMID- 18823056
TI  - Anion-responsive supramolecular gels.
AB  - Supramolecular gels that change their state or structure in response to anion
      stimuli have been highlighted. Only a few examples exist of such supramolecular
      gels, the structures and properties of which can be controlled and modulated by
      interactions with anions. To form anion-responsive dimensionally-controlled
      organized structures, the constituent low-molecular-weight gelator molecules must
      act as anion receptors by possessing one or more of van der Waals interaction
      units (aliphatic chains), stacking pi planes, hydrogen-bonding sites, and metal
      coordination units. This Concept focuses on the gelation and transition behaviors
      of amide- and urea-based anion-stimulated systems, metal-coordinated systems, and
      novel acyclic pi-conjugated oligopyrroles that act as "molecular flippers."

PMID- 18823057
TI  - Determinants of the unexpected stability of RNA fluorobenzene self pairs.

PMID- 18823058
TI  - A bacterial small molecule undermining immune response signaling.

PMID- 18823059
TI  - DMAP as an effective catalyst to accelerate the solubilization of waste fiber
      reinforced plastics.
AB  - Waste fiber-reinforced plastics (FRPs), which are formidable composite plastics
      for chemical treatment, can be efficiently depolymerized by treatment with
      supercritical methanol in the presence of catalytic amounts of 4
      (dimethylamino)pyridine (DMAP), which is a well-known catalyst for the formation
      of esters and amides. This novel depolymerization reaction also provides ready
      separation of the depolymerized products into three components: methanol-soluble
      oil, CHCl3-soluble solid, and an inorganic residue. Thus, almost complete
      decomposition of FRP as well as useful separation of the decomposed products was
      achieved with the present method, and the latter were ready for chemical
      recycling. Investigation of the reaction profile revealed that the reaction rate
      increased as the amount of DMAP increased. Unfortunately, DMAP employed in the
      reaction could not be recovered because of its decomposition catalyzed by
      dimethyl phthalate, a depolymerized product from waste FRP, under the reaction
      conditions employed.

PMID- 18823060
TI  - Multivariate analysis of toxicological and environmental properties of soil
      nematicides.
AB  - BACKGROUND: In intensive agriculture, the use of pesticides and soil fumigants is
      necessary to produce economically viable crops worldwide. However, this practice
      may involve undesirable effects on human health and the environment. In 1995,
      methyl bromide was restricted by the Montreal Protocol because of possible ozone
      depletion. The objective of this study was to compare intrinsic environmental and
      toxicological properties of 11 active substances with nematicidal properties,
      some of them recognized as methyl bromide alternatives. RESULTS: Four groups of
      active substances were discriminated by a series of principal component analyses
      (PCAs): (a) high toxicity to non-target fauna, humans and animals and medium
      persistence in the environment (cadusafos, ethoprophos and fenamiphos); (b) high
      toxicity to humans, animals and non-target fauna and high persistence (carbofuran
      and fosthiazate); (c) low toxicity to non-target fauna, humans and animals and
      low persistence (carbosulfan, benfuracarb and oxamyl); (d) low toxicity to
      humans, animals and non-target fauna and medium persistence in the environment
      (1,3-dichloropropene, chloropicrin and methyl bromide). CONCLUSION: Evaluating
      the multiple aspects of toxicological and environmental properties of active
      substances through PCA is proposed as a helpful tool for initially comparing the
      complex toxicological behaviour of active substances as plant protection
      products.

PMID- 18823061
TI  - Highly enantioselective copper-catalyzed ring opening of oxabicyclic alkenes with
      Grignard reagents.
AB  - A highly efficient copper-catalyzed enantioselective ring opening of oxabicylic
      alkenes with Grignard reagents has been developed by using chiral spiro phosphine
      ligands. Excellent trans selectivities, good yields, and high
      enantioselectivities are obtained for a broad range of Grignard reagents under
      mild reaction conditions. The catalyst system shows an extraordinary activity and
      the TON of the reaction reaches 9000.

PMID- 18823062
TI  - Denial in lung cancer patients: a longitudinal study.
AB  - BACKGROUND: Although denial in cancer patients is well known clinically, few
      studies investigating the prevalence of denial over time have been conducted. The
      objectives of this study are to investigate the level of denial in lung cancer
      patients over time and the impact of socio-demographic and illness-related
      variables on denial in these patients. METHODS: The level of denial was measured
      in 195 consecutive newly diagnosed lung cancer patients, using the Denial of
      Cancer Interview. Four assessments were conducted in eight months. Socio
      demographic data were collected during the interviews. Medical data were provided
      by the chest physicians. RESULTS: Most patients (86.6%) displayed a low or
      moderate level of denial at baseline. A small number (3%) showed a high level of
      denial. The mean level of denial was lowest at baseline and increased over time.
      Male lung cancer patients exhibited more denial than did female ones, and younger
      patients showed less denial than did the elderly. Shortly after diagnosis,
      patients with a lower level of education denied stronger than higher educated
      patients, and during the course of illness, both groups showed the same level of
      denial. CONCLUSION: A certain level of denial has to be considered a normal
      phenomenon in lung cancer patients, part of the illness process that they
      undergo. Whether the level of denial is related to adaptive or maladaptive coping
      remains to be investigated.

PMID- 18823064
TI  - Brief exposure of Blattella germanica (Blattodea) to insecticides formulated in
      various microcapsule sizes and applied on porous and non-porous surfaces.
AB  - BACKGROUND: The authors explored how microcapsule size and brief exposure
      affected the bioavailability of five microencapsulated insecticide formulations,
      chlorpyrifos 23.1 g L(-1) CS (Detmol-PRO), chlorpyrifos 20 g L(-1) CS (Empire
      20), fenitrothion 20 g L(-1) CS (Detmol-Mic), cyphenothrin 10 g L(-1) CS (Detmol
      CAP) and diazinon 30 g L(-1) CS (Diacap), to Blattella germanica L. on porous and
      non-porous surfaces. The hypothesis was tested that microencapsulated (CS)
      insecticides comprising larger microcapsules show higher efficacy on porous
      surfaces than formulations with smaller microcapsules. RESULTS: Brief exposure
      was accomplished by allowing B. germanica to cross a 0.3 m insecticide barrier in
      30 s (1.01 cm s(-1)). Such short exposure did not lead to 100% mortality in any
      formulation or surface tested. Significant differences in bioavailability on the
      porous and the non-porous surfaces were found: the largest difference was
      observed in Empire 20 and Detmol CAP, while bioavailability of Detmol MIC did not
      differ on porous and non-porous surfaces. Comparison of their microcapsule size
      spectra revealed that formulations containing larger microcapsules had higher
      efficacy on porous surfaces than formulations with smaller microcapsules. In
      order to explain the difference in efficacy, the variance of microcapsule sizes
      was regressed on the efficacy ratio on porous versus non-porous surfaces.
      Although negative correlation was evident between size of capsules and the
      efficacy ratio on porous and non-porous surfaces, the difference in the slope
      parameter was not statistically significant. CONCLUSION: Brief contact of B.
      germanica with insecticide spray residues, which is common in barrier treatment,
      may lead to low efficacy, especially on porous surfaces. The latter should be
      preferably treated with CS insecticides containing a fraction with large
      capsules. In addition to the size of the microcapsules, the role of other
      factors, such as wall capsule thickness and chemical composition, on CS
      insecticide activity on various surfaces should be examined in future work.

PMID- 18823065
TI  - Monitoring of Venturia inaequalis harbouring the QoI resistance G143A mutation in
      French orchards as revealed by PCR assays.
AB  - BACKGROUND: Genetic resistance to QoI fungicides may account for recent failures
      to control Venturia inaequalis (Cooke) Winter in French orchards. Two PCR-based
      assays were developed to detect the G143A point mutation in the fungal
      mitochondrial cytochrome b gene. The mutation is known to confer a high level of
      resistance to QoI fungicides. Occurrence of the G143A mutation in French field
      isolates collected from 2004 to 2007 was monitored. RESULTS: The QoI-resistant
      cytochrome b allele was specifically detected either following the cleavage of
      the amplified marker by a restriction endonuclease (CAPS assay) or its
      amplification using an allele-specific PCR primer. Using either method, the G143A
      mutation was found in 42% of the 291 field samples originating from French
      orchards in which apple scab proved difficult to be controlled. Monitoring of the
      G143A mutation in orchards located in 15 French administrative regions indicated
      that the mutation was detected at least once in nine of the regions, and its
      presence ranged from 33% to 64% of the orchards analysed in 2004 and in 2007
      respectively. CONCLUSION: The PCR-based methods developed in this study
      efficiently reveal the presence of the G143A mutation in French V. inaequalis
      field populations.

PMID- 18823066
TI  - Automatic sex detection of individuals of Ceratitis capitata by means of computer
      vision in a biofactory.
AB  - BACKGROUND: The sterile insect technique (SIT) is acknowledged around the world
      as an effective method for biological pest control of Ceratitis capitata
      (Wiedemann). Sterile insects are produced in biofactories where one key issue is
      the selection of the progenitors that have to transmit specific genetic
      characteristics. Recombinant individuals must be removed as this colony is
      renewed. Nowadays, this task is performed manually, in a process that is
      extremely slow, painstaking and labour intensive, in which the sex of individuals
      must be identified. The paper explores the possibility of using vision sensors
      and pattern recognition algorithms for automated detection of recombinants.
      RESULTS: An automatic system is proposed and tested to inspect individual
      specimens of C. capitata using machine vision. It includes a backlighting system
      and image processing algorithms for determining the sex of live flies in five
      high-resolution images of each insect. The system is capable of identifying the
      sex of the flies by means of a program that analyses the contour of the abdomen,
      using fast Fourier transform features, to detect the presence of the ovipositor.
      Moreover, it can find the characteristic spatulate setae of males. Simulation
      tests with 1000 insects (5000 images) had 100% success in identifying male flies,
      with an error rate of 0.6% for female flies. CONCLUSION: This work establishes
      the basis for building a machine for the automatic detection and removal of
      recombinant individuals in the selection of progenitors for biofactories, which
      would have huge benefits for SIT around the globe.

PMID- 18823067
TI  - New asperxanthone and asperbiphenyl from the marine fungus Aspergillus sp.
AB  - BACKGROUND: Marine fungi are of great importance as potential sources of
      agricultural pesticide leads. To continue work on new and biologically active
      metabolites from marine fungi, culture extracts of selected isolates were
      screened for inhibitory activity against tobacco mosaic virus (TMV), a typical
      member of the tobamovirus group of plant viruses. RESULTS: A new difuranxanthone,
      asperxanthone (1), and a new biphenyl, asperbiphenyl (2), as well as seven known
      unsaturated fatty acid glycerol esters, were isolated from a selected marine
      fungus, identified as Aspergillus sp. (MF-93), collected in the Quan-Zhou Gulf.
      Two-dimensional NMR methods and FAB-MS established the structures of the new
      compounds. Among the compounds, 1 and 2 showed moderate activity (inhibitory
      rates 62.9 and 35.5% respectively) in inhibiting multiplication of TMV, higher
      than that of the other seven known lipids but much lower than that of the extract
      at the identical concentration of 0.2 mg mL(-1). CONCLUSION: Two new compounds,
      asperxanthone and asperbiphenyl, were identified as active components from
      Aspergillus sp. (MF-93).

PMID- 18823068
TI  - Active drug safety surveillance: a tool to improve public health.
AB  - PURPOSE: Ensuring that drugs have an acceptable safety profile and are used
      safely is a major public health priority. The Centers for Education and Research
      on Therapeutics (CERTs) convened experts from academia, government, and industry
      to assess strategies to increase the speed and predictive value of generating and
      evaluating safety signals, and to identify next steps to improve the US system
      for identifying and evaluating potential safety signals. METHODS: The CERTs
      convened a think tank comprising representatives of the groups noted above to
      address these goals. RESULTS: Participants observed that, with the increasing
      availability of electronic health data, opportunities have emerged to more
      accurately characterize and confirm potential safety issues. The gain for public
      health from a highly coordinated network of population-based databases for active
      surveillance is great and within reach, although operational questions remain. A
      collaborative network must create a working definition of a safety signal,
      screening algorithms, and criteria and strategies to confirm or refute a signal
      once identified through screening. Guidelines are needed for when and how to
      communicate a signal exists and is being evaluated, as well as the outcome of
      that evaluation. CONCLUSION: A public-private partnership to create a network of
      government and private databases to routinely evaluate and prioritize safety
      questions is in the public interest. Better methods are needed, and a
      knowledgeable workforce is required to conduct the surveillance and understand
      how to interpret the results. The international community will benefit from the
      availability of better methods and more experts.

PMID- 18823069
TI  - Effects of an evidence report and policies lifting reimbursement restrictions for
      acid suppressants: analysis of the Belgian national database.
AB  - PURPOSE: To explore the effect on prescribing of policies that lift reimbursement
      restrictions on selected H2-antihistamines and proton pump inhibitors (PPI) and
      of practice recommendations. METHODS: Monthly claims based data for proton pump
      inhibitors (PPIs) and H2-antihistamines were obtained from the national health
      insurance database (Farmanet 1997-2005). Two policies were issued. In March 2001
      two H2-antihistamines and in March 2003 two PPIs became available without
      restrictions. An evidence report was distributed in September 2004. Periods
      before and after implementation of the interventions were compared. Interrupted
      time series with segmented regression analysis was used to assess and compare
      time trends. RESULTS: The first policy resulted in an increase of volume (1.6
      million DDDs; 95% CI 1.4-1.8 million; p < .001) and expenditure (euro 637,744;
      95% CI 177 052-1 098 437; p = .026) for H2-antihistamines, but consumption of
      PPIs continued to grow. After the second policy use of selected PPIs also
      increased (4.7 million DDDs increase; 95% CI 3.9-5.5 million; p < .001), but more
      than the desired shift toward selected PPIs. Although total expenditure
      stabilized at a lower level, there was no significant change of trend.
      Publication of the evidence report did not have any impact on prescribing.
      CONCLUSIONS: Policies that lift reimbursement restrictions did not result in
      meaningful changes in utilization or cost saving. They may even have unintended
      effects. Collaboration between policymakers and guideline developers and linking
      policies to evidence-based guidelines could be a more effective way to pursue
      cost-containment and better quality of care.

PMID- 18823070
TI  - Binding and elution strategy for improved performance of arginine affinity
      chromatography in supercoiled plasmid DNA purification.
AB  - New interesting strategies for plasmid DNA (pDNA) purification were designed,
      exploiting affinity interactions between amino acids and nucleic acids. The
      potential application of arginine-based chromatography to purify pDNA has been
      recently described in our work; however, to achieve higher efficiency and
      selectivity in arginine affinity chromatography, it is essential to characterize
      the behaviour of binding/elution of supercoiled (sc) isoforms. In this study, two
      different strategies based on increased sodium chloride (225-250 mm) or arginine
      (20-70 mm) stepwise gradients are described to purify sc isoforms. Thus, it was
      proved that well-defined binding/elution conditions are crucial to enhance the
      purification performance, resulting in an improvement of the final plasmids
      yields and transfection efficiency, as this could represent a significant impact
      on therapeutic applications of the purified sc isoform.

PMID- 18823071
TI  - An isocratic fluorescence HPLC assay for the monitoring of l-asparaginase
      activity and l-asparagine depletion in children receiving E. colil-asparaginase
      for the treatment of acute lymphoblastic leukaemia.
AB  - A novel assay for the determination of l-asparaginase activity in human plasma is
      described that is based on the HPLC quantitation of l-aspartic acid produced
      during enzyme incubation. Methods for monitoring l-asparagine depletion are also
      described. Chromatography of l-aspartic acid, l-asparagine and l-homoserine (the
      internal standard) involved derivatization with o-pthaldialdehyde, then
      separation from other amino acids on a Phenomenex Luna C(18) column using a 1
      mL/min flow rate and a mobile phase consisting of di-potassium hydrogen
      orthophosphate propionate buffer, pH 6, with 10% methanol and 10% acetonitrile.
      Fluoresence detection was at excitation/emission wavelengths of 357/455 nm. Under
      these conditions l-aspartic acid, l-asparagine and l-homoserine had retention
      times of 3.5, 9.8 and 17.7 min, respectively. The l-asparaginase assay was linear
      from 0.1 to 10 U/mL activity and interday precision and accuracy were less than
      13%. The limit of quantitation was approximately 0.03 U/mL. The assay utility was
      established in 12 children who received E. coli l-asparaginase as treatment for
      acute lymphoblastic leukaemia.

PMID- 18823072
TI  - A rapid and specific approach for direct measurement of donepezil concentration
      in human plasma by LC-MS/MS employing solid-phase extraction.
AB  - A selective, rapid and simple liquid chromatography-tandem mass spectrometry (LC
      MS/MS) method is described for assay of donepezil in human plasma using
      escitalopram as an internal standard. Chromatographic separation was achieved on
      a Betabasic-C(8), 5 microm, 100 x 4.6 mm column using methanol:water:formic acid
      (90:9.97:0.03, v/v/v) as mobile phase. Detection of donepezil and internal
      standard was achieved by ESI MS/MS in positive ion mode using 380.20/91.10 and
      325.13/262.00 transitions, respectively. The linearity over the concentration
      range of 0.15-50 ng/mL for donepezil was obtained and the lower limit of
      quantification was 0.15 ng/mL. For each level of quality control samples, inter
      day and intra-day precisions (RSD) were < or =8.92 and 10.35% and accuracy (%RE)
      were < or =7.33% and 9.33%, respectively. The recovery was more than 88.50% for
      both donepezil and internal standard by solid-phase extraction, eliminating
      evaporation and reconstitution steps.

PMID- 18823073
TI  - Determination of halofantrine and its main metabolite desbutylhalofantrine in rat
      plasma by high-performance liquid chromatography with on-line UV irradiation and
      peroxyoxalate chemiluminescence detection.
AB  - A sensitive, selective and reliable method has been developed and validated for
      the determination of halofantrine and its metabolite desbutylhalofantrine in rat
      plasma using 9,10-diphenylanthracene as an internal standard. The method is based
      on peroxyoxalate chemiluminescence detection of hydrogen peroxide produced from
      fused aromatic rings in the structures of halofantrine and desbutylhalofantrine
      upon UV irradiation. Using spiked rat plasma, good linear relationships were
      obtained for both halofantrine and desbutylhalofantrine between peak height
      ratios (vs internal standard) and their corresponding concentrations over a range
      of 0.01-0.8 microg/mL with correlation coefficients of at least 0.997. The
      detection limits at signal-to-noise ratio of 3 using 0.2 mL of rat plasma were
      1.5 and 1.4 ng/mL for halofantrine and desbutylhalofantrine, respectively.
      Relative standard deviations (n = 3) intra- and inter-day were between 0.5 and
      5.4% for all the studied concentrations. Using this method with simple sample
      treatment, halofantrine and desbutylhalofantrine in rat plasma could be precisely
      determined without interference from endogenous substances. The method was
      successfully applied to the measurement of the time courses of plasma
      halofantrine concentration after oral administration of the drug (7 mg/kg) to
      rats.

PMID- 18823074
TI  - Determination of acyclovir in horse plasma and body fluids by high-performance
      liquid chromatography combined with fluorescence detection and heated
      electrospray ionization tandem mass spectrometry.
AB  - Two methods are presented for the determination of 'respectively' the plasma
      protein unbound and total concentration of acyclovir in horse plasma and body
      fluids: first, a liquid-liquid extraction was performed on plasma, combined with
      HPLC-fluorescence detection for the total plasma concentration; second a more
      sensitive method using high-performance liquid chromatography combined with
      heated electrospray ionization tandem mass spectrometry (LC-HESI-MS/MS) was
      described for plasma and for body fluids analysis. To obtain the unbound
      concentration of acyclovir in plasma, a simple deproteinization step using a
      Microcon filter was performed. Ganciclovir was used as an internal standard.
      Analysis was carried out on an Inertsil 5 ODS-3 column for the HPLC-fluorescence
      method. For the LC-HESI-MS/MS method a PLRP-S column was used. The limit of
      quantification (LOQ) for the total concentration was set at 50 and 2 ng mL(-1)
      for the HPLC-fluorescence method and the LC-HESI-MS/MS method, respectively. The
      limit of quantification for the unbound concentration was set at 5 ng mL(-1) and
      at 2 ng mL(-1) for body fluids. The methods were successfully used to perform
      pharmacokinetic and clinical studies in horses after intravenous and oral dosage
      of acyclovir and its prodrug valacyclovir.

PMID- 18823075
TI  - The phytochemical analysis and antioxidant activity assessment of orange peel
      (Citrus sinensis) cultivated in Greece-Crete indicates a new commercial source of
      hesperidin.
AB  - The flavonoid content of several methanolic extract fractions of Navel orange
      peel (flavedo and albedo of Citrus sinensis) cultivated in Crete (Greece) was
      first analysed phytochemically and then assessed for its antioxidant activity in
      vitro. The chemical structures of the constituents fractionated were originally
      determined by comparing their retention times and the obtained UV spectral data
      with the available bibliographic data and further verified by detailed LC-DAD-MS
      (ESI+) analysis. The main flavonoid groups found within the fractions examined
      were polymethoxylated flavones, O-glycosylated flavones, C-glycosylated flavones,
      O-glycosylated flavonols, O-glycosylated flavanones and phenolic acids along with
      their ester derivatives. In addition, the quantitative HPLC analysis confirmed
      that hesperidin is the major flavonoid glycoside found in the orange peel.
      Interestingly enough, its quantity at 48 mg/g of dry peel permits the commercial
      use of orange peel as a source for the production of hesperidin. The antioxidant
      activity of the orange peel methanolic extract fractions was evaluated by
      applying two complementary methodologies, DPPH(*) assay and the Co(II)/EDTA
      induced luminol chemiluminescence approach. Overall, the results have shown that
      orange peel methanolic extracts possess moderate antioxidant activity as compared
      with the activity seen in tests where the corresponding aglycones, diosmetin and
      hesperetin were assessed in different ratios.

PMID- 18823076
TI  - HPLC-UV assay for monitoring total and unbound mycophenolic acid concentrations
      in children.
AB  - A simple, accurate and sensitive HPLC method was developed for measuring total
      and unbound mycophenolic acid (MPA) in human plasma. Total MPA was extracted by
      protein precipitation and ultrafiltration was used to assess unbound MPA
      concentrations. The supernatant (20 microL) or ultrafiltrate (100 microL) was
      injected onto a C(18) HPLC column with a mobile phase of 0.05 m sodium phosphate
      buffer (pH 2.31)-acetonitrile (55:45, v/v for total MPA; 50:50 for unbound MPA)
      with UV detection at 254 nm. The extraction recovery was over 93% and
      reproducible. The assay was linear over the concentration range of 0.07-50 mg/L
      for total MPA and 4-1500 microg/L for unbound MPA. Intra- and inter-day assay
      reproducibility was less than 10%. Detection limits were 0.04 mg/L and 2 microg/L
      for total and unbound MPA, respectively. The assay utility was established in
      samples collected from five paediatric bone marrow transplant recipients who were
      receiving intravenous doses of mycophenolate mofetil. In these patients MPA
      concentrations ranged from 0.07 to 7.83 mg/L and unbound drug concentrations
      ranged from 2.1 to 107.5 microg/L. This method can be effectively applied to MPA
      pharmacokinetics in paediatric patients.

PMID- 18823077
TI  - The 'Distress Barometer': validation of method of combining the Distress
      Thermometer with a rated complaint scale.
AB  - OBJECTIVE: Screening instruments may enhance the clinician's ability to detect
      elevated levels of distress in cancer patients, but these are often neither
      suitable nor effective for the routine of daily care for cancer patients. The
      newly developed Distress Barometer (DB) was intended to provide medical doctors
      with a convenient tool to interpret 'at single glance' the nature and the
      intensity of distress in ambulatory cancer patients. The DB, i.e. a combination
      of the Distress Thermometer (DT) and a new tool, the Colored Complaint Scale was
      developed to improve the specificity of distress screening without decreasing the
      sensitivity of the Distress Thermometer. METHODS: Distress was screened in a
      sample of 538 out-patients, using the Hospital Anxiety and Depression Scale
      (HADS) and the new Distress Barometer (DB). RESULTS: The results confirm the
      validity of the Dutch version of the DT against the HADS as standard measure. In
      addition, it was found that the overall accuracy of the new DB was higher, with a
      sensitivity of 0.79 and a specificity of 0.81. CONCLUSION: These results indicate
      that the Distress Barometer, which is convenient for both patients and doctors,
      can be used as an acceptable, brief and sufficiently accurate method for
      detecting distress in cancer patients.

PMID- 18823078
TI  - Entomopathogens (Beauveria bassiana and Steinernema carpocapsae) for biological
      control of bark-feeding moth Indarbela dea on field-infested litchi trees.
AB  - BACKGROUND: The bark-feeding moth Indarbela dea (Swinhoe) is one of the major
      pests of litchi (Litchi chinensis Sonn.) in Asia. Effects on larval mortality and
      web production were tested by repeated, single and combined tree trunk
      applications of the entomopathogenic fungus Beauveria bassiana (Bals.) Vuill. and
      the entomopathogenic nematode Steinernema carpocapsae (Weiser). Two separate
      application trials were conducted in different seasons on young and older larvae
      respectively. RESULTS: In both trials, complete or nearly complete mortality
      (100% and 95%) of the larvae was achieved 3 weeks after application of S.
      carpocapsae alone and 2 weeks after the combined application of B. bassiana and
      S. carpocapsae (100% in both trials). However, in the combined application, all
      larvae were killed by one treatment, while the application of S. carpocapsae
      alone needed to be repeated to reach the same result. The effectiveness of the
      combined entomopathogen application and of the application of S. carpocapsae
      alone was not influenced by the age of the larvae. However, the single
      applications of B. bassiana were only effective on young larvae. In both trials,
      web production of surviving larvae was very significantly reduced by the
      application of S. carpocapsae in single and combined treatments. CONCLUSIONS: As
      the results show, only one application is necessary in the combined application
      of the two entomopathogens to control I. dea, which implies that such treatment
      is probably the economically most relevant solution.

PMID- 18823079
TI  - Watsu approach for improving spasticity and ambulatory function in hemiparetic
      patients with stroke.
AB  - BACKGROUND AND PURPOSE: This study reports the effect of Watsu as rehabilitation
      method for hemiparetic patients with stroke. METHOD: Watsu consisted of 40
      treatment sessions for 8 weeks, delivered underwater or at water surface level,
      it applied in three patients. Outcome measures included tools for assessing
      spasticity and ambulatory function. RESULTS: All patients showed decreased scores
      in the TAS and RVGA after Watsu application. CONCLUSIONS: Watsu was helpful in
      controlling spasticity and improving ambulatory function of the patients with
      hemiparesis.

PMID- 18823080
TI  - Dual types of spherulites in poly(octamethylene terephthalate) confined in thin
      film growth.
AB  - Spherulite morphology and growth kinetics of poly(octamethylene terephthalate)
      (POT), cast on single-side glass or confined between two slides in thin-film
      forms, were characterized using polarized versus nonpolarized optical microscopy,
      scanning electron microscopy (SEM), and wide-angle X-ray (WAXD) analysis. POT can
      simultaneously display solely one type of spherulite or dual types of spherulites
      (double-ring-banded and ringless ones), depending on T c or T max imposed.
      Fractions of these two types depend on T c when quenched from a fixed T max = 160
      degrees C. At lower T c's, POT exhibits higher crystallization rates leading to
      higher fractions of ringless spherulites; at higher T c's, POT exhibits lower
      crystallization rates leading to ring-banded spherulites. At intermediate to high
      T c's where the growth kinetics of POT could be monitored, the ring-band type
      dominates and the fraction of ringless spherulites is insignificantly small. Both
      ringless and ring-banded spherulites can be seen in regime III ( T c = 70-110
      degrees C), with fractions of ringless type of spherulites decreasing with
      temperature. Thus, growth kinetics for POT was mainly focused on the regime of
      ring-banded spherulites. In regime III, the ring-band pattern is more orderly
      concentric with smaller inter-ring spacing (1-2 mum) for lower T c's but
      intermediately larger spacing (3-5 mum) for higher T c's. The orderly lamellar
      orientation in the ring-bands in contrast with the inter-ring valley region is
      discussed. In regime II (115 degrees C and above), the ring-band pattern is first
      distorted to highly zigzag irregularity at higher T c's and then eventually
      disappears at extremely high T c, with the lamellar crystals eventually turning
      dendritic with no rings. Apparently, the types of spherulites in polymers are
      more influenced by the growth rates as determined by T c and slightly less by T
      max, but not by the substrate surface nucleation.

PMID- 18823081
TI  - Comparison of electron-transfer rates for metal- versus ring-centered redox
      processes of porphyrins in monolayers on Au(111).
AB  - The standard electron-transfer rate constants ( k ( 0 )) are measured for redox
      processes of Fe versus Zn porphyrins in monolayers on Au(111); the former
      undergoes a metal-centered redox process (conversion between Fe (III) and Fe (II)
      oxidation states) whereas the latter undergoes a ring-centered redox process
      (conversion between the neutral porphyrin and the pi-cation radical). Each
      porphyrin contains three meso-mesityl groups and a benzyl thiol for surface
      attachment. Under identical solvent (propylene carbonate)/electrolyte (1.0 M Bu
      4NCl) conditions, the Zn (II) center has a coordinated Cl (-) ion when the
      porphyrin is in either the neutral or oxidized state. In the case of the Fe
      porphyrin, two species are observed a low-potential form ( E l (0) approximately 
      0.6 V) wherein the metal center has a coordinated Cl (-) ion when it is in either
      the Fe (II) or Fe (III) state and a high-potential form ( E h (0) approximately
      +0.2 V) wherein the metal center undergoes ligand exchange upon conversion from
      the Fe (III) to Fe (II) states. The k ( 0 ) values observed for all of the
      porphyrins depend on surface concentration, with higher concentrations resulting
      in slower rates, consistent with previous studies on porphyrin monolayers. The k
      ( 0 ) values for the ring-centered redox process (Zn chelate) are 10-40 times
      larger than those for the metal-centered process (Fe chelate); the k ( 0 ) values
      for the two forms of the Fe porphyrin differ by a factor of 2-4 (depending on
      surface concentration), the Cl (-) exchanging form generally exhibiting a faster
      rate. The faster rates for the ring- versus metal-centered redox process are
      attributed to the participating molecular orbitals and their proximity to the
      surface (given that the porphyrins are relatively upright on the surface): a pi
      molecular orbital that has significant electron density at the meso-carbon atoms
      (one of which is the site of attachment of the linker to the surface anchoring
      thiol) versus a d-orbital that is relatively well localized on the metal center.

PMID- 18823082
TI  - Adsorption and stability of streptavidin on cluster-assembled nanostructured TiOx
      films.
AB  - The study of the adsorption of proteins on nanostructured surfaces is of
      fundamental importance to understand and control cell-surface interactions and,
      notably, cell adhesion and proliferation; it can also play a strategic role in
      the design and fabrication of nanostructured devices for postgenomic and
      proteomic applications. We have recently demonstrated that cluster-assembled
      nanostructured TiO x films produced by supersonic cluster beam deposition possess
      excellent biocompatibility and that these films can be functionalized with
      streptavidin, allowing the immobilization of biotinylated retroviral particles
      and the realization of living-cell microarrays for phenotype screening. Here we
      present a multitechnique investigation of the adsorption mechanisms of
      streptavidin on cluster-assembled TiO x films. We show that this nanostructured
      surface provides an optimal balance between adsorption efficacy and protein
      functionality. By using low-resolution protein arrays, we demonstrate that a
      layer of adsorbed streptavidin can be stably maintained on a cluster-assembled
      TiO x surface under cell culture conditions and that streptavidin retains its
      biological activity in the adsorbed layer. The adsorption mechanisms are
      investigated by atomic force microscopy in force spectroscopy mode and by valence
      band photoemission spectroscopy, highlighting the potential role of the
      interaction of the exposed carboxyl groups on streptavidin with the titanium
      atoms of the nanostructured surface.

PMID- 18823083
TI  - Aggregation of a peptide antibiotic alamethicin at the air-water interface and
      its influence on the viscoelasticity of phospholipid monolayers.
AB  - The aggregation properties of an antibiotic membrane-active peptide alamethicin
      at the air-water interface have been studied using interfacial rheology and
      fluorescence microscopy techniques. Fluorescence microscopy of alamethicin
      monolayers revealed a coexistence of liquid expanded (LE) and solid phases at the
      surface concentrations studied. Interfacial oscillatory shear measurements on
      alamethicin monolayers indicate that its viscoelastic properties are determined
      by the area fraction of the solid domains. The role of zwitterionic phospholipids
      dioleoylphosphatidyl choline (DOPC) and dioleoylphosphatidyl ethanolamine (DOPE)
      on the peptide aggregation behavior was also investigated. Fluorescence
      microscopy of alamethicin/phospholipid monolayers revealed an intermediate phase
      (I) in addition to the solid and LE phase. In mixed monolayers of phospholipid
      (L)/alamethicin (P), with increase in L/P, the monolayer transforms from a
      viscoelastic to a viscous fluid with the increase in area fraction of the
      intermediate phase. Further, a homogeneous mixing of alamethicin/lipid molecules
      is observed at L/P > 4. Our studies also confirm that the viscoelasticity of
      alamethicin/phospholipid monolayers is closely related to the
      alamethicin/phospholipid interactions at the air-water interface.

PMID- 18823084
TI  - Nanografting versus solution self-assembly of alpha,omega-alkanedithiols on
      Au(111) investigated by AFM.
AB  - The solution self-assembly of alpha,omega-alkanedithiols onto Au(111) was
      investigated using atomic force microscopy (AFM). A heterogeneous surface
      morphology is apparent for 1,8-octanedithiol and for 1,9-nonanedithiol self
      assembled monolayers (SAMs) prepared by solution immersion as compared to methyl
      terminated n-alkanethiols. Local views from AFM images reveal a layer of mixed
      molecular orientations for alpha,omega-alkanedithiols, which evidence surface
      structures with heights corresponding to both lying-down and standing-up
      orientations. For dithiol SAMs prepared by solution self-assembly, the majority
      of alpha,omega-alkanedithiol molecules chemisorb with both thiol end groups bound
      to the Au(111) surface with the backbone of the alkane chain aligned parallel to
      the surface. However, AFM images disclose that there are also islands of standing
      molecules scattered throughout the surface. To measure the thickness of
      alpha,omega-alkanedithiol SAMs with angstrom sensitivity, methyl-terminated n
      alkanethiols with known dimensions were used as molecular rulers. Under
      conditions of spatially constrained self-assembly, nanopatterns of alpha,omega
      alkanedithiols written by nanografting formed monolayers with heights
      corresponding to an upright configuration.

PMID- 18823085
TI  - Correlation between the molecular structure and photoresponse in aliphatic self
      assembled monolayers with azobenzene tailgroups.
AB  - We have compared the structural and photoisomerization properties of self
      assembled monolayers (SAMs) comprising either the trans or cis isomers of
      azobenzene terminated dithiolane with in-chain amide unit, viz., 4
      (phenyldiazenyl)phenyl-4-(1,2-dithiolane-3-yl)-butylcarboxamide ( 1). These films
      were prepared on Au(111) from solutions of both isomers. Structure and
      composition of the SAMs were studied by X-ray photoelectron spectroscopy and near
      edge X-ray absorption fine structure spectroscopy. The photoresponse of the films
      was monitored in real time by ellipsometry. SAMs fabricated from the trans isomer
      were found to be densely packed and highly ordered. These films did not show any
      discernible photoresponse upon irradiation with UV light, which, under favorable
      conditions, triggers the trans- cis isomerization. In contrast, films prepared
      from solutions containing predominantly the cis isomer were loosely packed and
      mostly disordered but exhibited reversible photoreactivity. The results confirm
      that steric effects, i.e., available free volume, play a dominant role for the
      photoresponse of aliphatic SAMs bearing the photoactive azobenzene group. The
      crystal structure of 1 ( trans isomer) exhibits a row-like aggregation of
      neighboring molecules by weak hydrogen bonds and can be taken as a model for the
      arrangement of 1 in the monolayer films. Further, in addition to the surface
      coordination behavior, we have also mimicked the chemisorption of the 1,2
      dithiolane moiety onto the gold substrate in molecular coordination chemistry in
      oxidative addition reactions with the zero-valent platinum complex [Pt(PPh 3) 4].

PMID- 18823086
TI  - Monolayers of 3-mercaptopropyl-amino acid to reduce the nonspecific adsorption of
      serum proteins on the surface of biosensors.
AB  - Monolayers prepared with polar or ionic amino acids with short side chains have a
      reduced nonspecific adsorption of serum proteins compared to that of hydrophobic
      amino acids and organic monolayers immobilized on the gold surface of surface
      plasmon resonance (SPR) biosensors. Proteins contained in biological samples
      adsorb on most surfaces, which in the case of biosensors causes a nonspecific
      response that hinders the quantification of biomarkers in these biological
      samples. To circumvent this problem, self-assembled monolayers (SAM) of N-3
      mercaptopropyl-amino acids (3-MPA-amino acids) were prepared from 19 natural
      amino acids. These SAM were investigated to limit the nonspecific adsorption of
      proteins contained in biological fluids and to immobilize molecular receptors
      (i.e., antibodies) that are necessary in the construction of biosensors. SPR and
      Ge attenuated total reflection (GATR) FTIR spectroscopy were employed to
      characterize the formation of the amino acid SAMs. Monolayers of 3-MPA-amino
      acids densely packed on the surface of the SPR biosensors result in a surface
      concentration of approximately 10 (15) molecules/cm (2). SPR also quantifies the
      surface concentration of serum proteins nonspecifically adsorbed on 3-MPA-amino
      acids following the exposure of the biosensor to undiluted bovine serum. The
      concentration of nonspecifically bound proteins ranged from approximately 400
      ng/cm (2) with polar and ionic amino acids to approximately 800 ng/cm (2) with
      amino acids of increased hydrophobicity. The nonspecific adsorption of serum
      proteins on the 3-MPA-amino acids increases in the following order: Asp < Asn <
      Ser < Met < Glu < Gln < Thr < Gly < His < Cys < Arg < Phe < Trp < Val < Pro < Ile
      < Leu < Ala < Tyr. The analysis of the adsorption and desorption curves for serum
      proteins on the SPR sensorgram has demonstrated the strong irreversibility of the
      protein adsorption on each surface. The effective hydrophilicity of the SAMs was
      measured from the contact angle with a saline buffer and has demonstrated that
      surfaces minimizing the contact angle with PBS performed better in serum. The
      antibody for beta-lactamase was immobilized on a 3-MPA-glycine SAM, and beta
      lactamase was detected in the nanomolar range. The presence of beta-lactamase is
      an indicator of antibiotic resistance.

PMID- 18823087
TI  - Motion picture imaging of a nanometer-thick liquid film dewetting by
      ellipsometric microscopy with a submicrometer lateral resolution.
AB  - We visualized the detwetting of a nanometer-thick unstable liquid film on a
      nanotextured solid surface with a high lateral spatial resolution. The dewetting
      was imaged as a motion picture at a submicrometer spatial resolution and a frame
      rate of 4 frames/s, using ellipsometric microscopy in a vertical objective
      configuration. The observation revealed that the dewetting process significantly
      depends on the sign of the disjoining pressure Pi. When Pi is negative, the film
      rupture due to the spinodal dewetting proceeds to droplet formation in a single
      step, whereas, when Pi is positive, the film rupture due to the spinodal
      dewetting stops when the pressure of the thicker region balances with that of the
      thinner region, and then the heterogeneous grooves are nucleated and grow. The
      dewetting process dependence on the sign of Pi can be found in systems other than
      that reported here because the sign of Pi changes at the local maximum of the
      surface energy.

PMID- 18823088
TI  - Confinement of DNA in water-in-oil microemulsions.
AB  - The study of systems that allow DNA condensation in confined environments is an
      important task in producing cell-mimicking microreactors capable of biochemical
      activities. The water droplets formed in water-in-oil emulsions are potentially
      good candidates for such microcompartments. The anionic surfactant AOT was used
      here to stabilize the droplets. We have studied in detail the DNA distribution
      and the structural modifications of these microemulsion drops by varying the
      concentration and molecular weight of DNA and using various techniques such as
      light, X-ray, and neutron scattering, electrical conductivity, and surface
      tension. DNA induces the formation of large drops into which it is internalized.
      The size of these drops depends on the amount of DNA dissolved in water as well
      as on its molecular weight. The local DNA concentration is very high (>100
      mg/mL). The large drops coexist with small empty drops (not containing DNA),
      similar to those found in the DNA-free microemulsion.

PMID- 18823089
TI  - Composites of kaolin and polydimethylsiloxane.
AB  - Kaolin particles were surface-treated with isobutyltrimethoxysilane (IBTMS),
      hydrogenated tallow (HT), and a polyisobutyl chain-based stabilizer (SAP) to make
      composites with polydimethylsiloxane (PDMS). IBTMS did not cover the strong acid
      sites on the kaolin surface and as a result a cross-linking reaction occurred for
      silanol-terminated PDMS. The polyisobutyl chain of SAP was found to be
      incompatible with PDMS and this caused aggregation of the kaolin particles. HT
      was the most effective at dispersing the particles into silanol-terminated PDMS.
      The aggregation state of the composites was characterized using rheology and
      microscopy. Both showed the HT-treated particles were well-dispersed in low
      molecular weight silanol-terminated PDMS, and they were weakly flocculated in
      higher molecular weight silanol-terminated PDMS. However, the same particles
      aggregated when dispersed in methyl-terminated PDMS. It appears the silanol
      terminated PDMS acted as costabilizer through interaction with the kaolin
      surface. Transverse relaxation NMR was used to probe mobility of the PDMS chains
      in the composites. This showed little dependence on surface treatment,
      aggregation state, or polymer end groups. For all samples, chain mobility
      decreased with increasing kaolin concentration.

PMID- 18823090
TI  - Synthesis and characterization of polydiacetylene films and nanotubes.
AB  - We report here the synthesis and characterization of polydiacetylene (PDA) films
      and nanotubes using layer-by-layer (LBL) chemistry. 10,12-Docosadiyndioic acid
      (DCDA) monomer was self-assembled on flat surfaces and inside of nanoporous
      alumina templates. UV irradiation of DCDA provided polymerized-DCDA (PDCDA) films
      and nanotubes. We have used zirconium-carboxylate interlayer chemistry to
      synthesize PDCDA multilayers on flat surfaces and in nanoporous template. PDCDA
      multilayers were characterized using optical (UV-vis, fluorescence, ellipsometry,
      FTIR) spectroscopies, ionic current-voltage ( I- V) analysis, and scanning
      electron microscopy. Ellipsometry, FTIR, electronic absorption and emission
      spectroscopies showed a uniform DCDA deposition at each deposition cycle. Our
      optical spectroscopic analysis indicates that carboxylate-zirconium interlinking
      chemistry is robust. To explain the disorganization in the alkyl portion of PDCDA
      multilayer films, we propose carboxylate-zirconium interlinkages act as "locks"
      in between PDCDA layers which restrict the movement of alkyl portion in the
      films. Because of this locking, the induced-stresses in the polymer chains can
      not be efficiently relieved. Our ionic resistance data from I- V analysis
      correlate well with calculated resistance at smaller number of PDCDA layers but
      significantly deviated for thicker PDCDA nanotubes. These differences were
      attributed to ion-blocking because some of the PDCDA nanotubes were totally
      closed and the nonohmic and permselective ionic behaviors when the diameter of
      the pores approaches the double-layer thickness of the solution inside of the
      nanotubes.

PMID- 18823091
TI  - Regulation of pattern dimension as a function of vacuum pressure: alkyl monolayer
      lithography.
AB  - Photopatterning of a hexadecyl (HD) monolayer has been demonstrated using vacuum
      ultraviolet (VUV; lambda = 172 nm) light under controlled vacuum pressure with
      the objective of minimizing the pattern dimension. X-ray photoelectron
      spectroscopy (XPS) and lateral force microscopy (LFM) studies reveal that
      photodegradation of the HD monolayer not only is limited to the regions exposed
      to VUV but also spreads under the masked regions. The strong oxidants generated
      by VUV irradiation to atmospheric oxygen and water vapor diffuse toward the
      masked regions through the nanoscopic channels and photodissociate the monolayer
      under the masked area, near the photomask apertures, resulting in broadening of
      the photopattern. Such broadening decreases with decreased vacuum pressure inside
      the VUV chamber, associated with a decrease of oxidant concentration and
      reduction of their diffusion. Gold nanoparticles (AuNPs) were immobilized on the
      VUV patterned features to probe the dimension of the chemically active pattern.
      Field emission electron microscopy reveals the construction of 565 nm wide
      pattern features at a vacuum pressure of 10 Pa. This pattern widens to 1,030 nm
      at 10 (4) Pa using the same size apertures (500 nm) as printed on the photomask.
      This study provides insight for fabricating submicron patterns with high
      reproducibility and its exploitation for different applications, which includes
      the patterning of nanoparticles, biopolymers, and other nano-objects at submicron
      dimensions.

PMID- 18823092
TI  - Synthesis and assembly of gold nanoparticles in organized molecular films of
      gemini amphiphiles.
AB  - Generation and assembly of gold nanostructures were investigated in the organized
      molecular films of a series of gemini amphiphiles. The chloroauric acid,
      dissolved in the aqueous subphase, was incorporated into the monolayers of the
      gemini amphiphiles containing ethyleneamine spacers through an interfacial
      assembly. The in situ formed complex monolayers were transferred onto solid
      substrates, and gold nanoparticles were generated in the film by a chemical or
      photochemical reduction. Discrete gold nanoparticles with an absorption maximum
      at 550 nm were generated in the films by photoirradiation, while different gold
      nanostructures were obtained by chemical reduction. Depending on the chemical
      reductant, various shape and assembly of gold nanostructures were obtained. When
      reduced by hydroquinone, a tree-branched assembly of the nanoparticles was
      obtained and the film showed a broad band centered at around 900 nm. When NaBH 4
      was applied, crooked nanowires or assembly of nanoparticles were obtained,
      depending on concentration, and the film showed absorption at 569 or 600 nm.
      Furthermore, by combining the photochemical and chemical reduction methods, i.e.,
      the chloroaurate ion-incorporated film was initially irradiated with UV light and
      then subjected to chemical reduction, the optical absorption of the formed gold
      nanostructures can be regulated.

PMID- 18823093
TI  - Transmembrane delivery of the cell-penetrating peptide conjugated semiconductor
      quantum dots.
AB  - Conjugation of the cell-penetrating peptide derived from the human
      immunodeficiency virus-1 transactivator protein (TAT) to semiconductor quantum
      dots (QDs) is an effective way to enhance transmembrane delivery of QDs for
      intracellular and molecular imaging. In this work, the internalization pathway of
      TAT-QDs was studied systematically in living cells. Cellular uptake of TAT-QDs,
      under different endocytosis-inhibiting conditions, was compared by fluorescence
      imaging and flow cytometry. The results suggest TAT-QDs internalize through lipid
      raft-dependent macropinocytosis, which is different from that of FITC-labeled
      TAT. They also provide new information for better understanding of the TAT
      mediated cell uptake mechanism.

PMID- 18823094
TI  - Influence of substrate heating on the evaporation dynamics of pinned water
      droplets.
AB  - The dynamics of evaporating water droplets deposited on a heated substrate is
      investigated numerically. Droplets are pinned with a contact line radius of R = 1
      mm. Evaporative mass flow and convection occurring inside the droplets are
      studied for different heating substrate sizes L S and heating temperatures T S. A
      simplified model neglecting hydrodynamics in air and evaporative cooling and
      assuming droplets to be spherical caps is simulated with a finite element method.
      A toruslike convective cell appears inside the droplets as evaporation takes
      place. For L S/ R > 1, the contact line is warmer than the apex of the droplets,
      and convection generates a downstream flow in the vicinity of the symmetry axis
      of the droplets. For L S/ R < 1, it is the apex that is warmer. Convection then
      generates an upstream flow. The overall evaporation time is described. It slows
      when L S/ R > 1.

PMID- 18823095
TI  - Microfluidic production of droplet pairs.
AB  - We study a microfluidic dual nozzle for the production of water-in-oil droplet
      pairs. Droplets are paired by the hydrodynamic coupling of two nozzles over a
      wide range of aqueous and oil flow rates provided that they are larger than the
      channel dimensions. The droplet production frequencies and volumes are related to
      the flow rates through a single, experimentally determined power-law. The data
      are in good agreement with a model based on a geometrical decomposition of the
      dual nozzle leading to a general equation of droplet frequencies as a function of
      the various flow rates.

PMID- 18823096
TI  - Quantitation of surface-reducing-end covalently bound polysaccharides via
      hydrazinolysis and deamination.
AB  - Depending on the method of deposition, reactive sites of polysaccharides on
      substrates may not be available when their reducing ends have been used to
      covalently bind them to the substrates. Here we present a method that allows
      surface density measurements of reducing-end covalently bound polysaccharides in
      a procedure that cleaves the polysaccharide chain from the surface via
      hydrazinolysis and deamination, leaving on the surface a disaccharide that is
      later radiolabeled with an aldehyde in a reaction with enamine formation. The
      method described has the advantage that it may be used with any polysaccharide
      patterned to any surface exposing an amino-terminated monolayer by reductive
      amination of their galactosamine or glucosamine repeating units. We illustrate
      the technique with the quantitation of glycosaminoglycans (GAGs) on silanized
      glass surfaces.

PMID- 18823097
TI  - Some physicochemical aspects of nanoparticulate magnetic iron oxide colloids in
      neat water and in the presence of poly(vinyl alcohol).
AB  - The preparation of magnetic iron oxide colloids directly from the coprecipitation
      of Fe (2+) and Fe (3+) species at different temperatures may lead to crystallites
      of higher size as the temperature of the reaction increases. On the other hand,
      dynamic light scattering investigations and dielectric measurements rather point
      to the similar colloidal size of the entities existing in their aqueous or solid
      state dispersions, irrespective of the size of the primary nanocrystallites.
      Significant enhancement of the stability of the colloids, even in the presence of
      high electrolyte concentrations, is furnished after the addition of relatively
      small amounts of poly(vinyl alcohol), and the stabilization mechanism is
      discussed in terms of the various forces participating in the system. The
      experimental results suggest that the increased colloidal stability is triggered
      from the particles' decrease of velocity rather than from steric (entropic)
      effects originating from polymer absorption.

PMID- 18823098
TI  - Heats of formation of HCCl3, HCCl2Br, HCClBr2, HCBr3, and their fragment ions
      studied by threshold photoelectron photoion coincidence.
AB  - The dissociative photoionization onsets for Cl and Br loss reactions were
      measured for HCCl3, HCCl2Br, HCClBr2, and HCBr3 by threshold photoelectron
      photoion coincidence (TPEPICO) in order to establish the heats of formation of
      the mixed halides as well as the following fragment ions: HCCl2(+), HCClBr(+),
      HCBr2(+). The first zero Kelvin onsets were measured with a precision of 10 meV.
      The second onsets, which are in competition with the lower energy onsets, were
      established with a precision of 60 meV. Because both the chloroform and bromoform
      have relatively well established heats of formation, these measurements provide a
      route for establishing the heats of formation of the mixed halomethanes within
      uncertainties of less than 5 kJ mol(-1).

PMID- 18823099
TI  - Pyrolysis of methyl tert-butyl ether (MTBE). 1. Experimental study with molecular
      beam mass spectrometry and tunable synchrotron VUV photoionization.
AB  - An experimental study of methyl tert-butyl ether (MTBE) pyrolysis (3.72% MTBE in
      argon) has been performed at low pressure (267 Pa) within the temperature range
      from 700 to 1420 K. The pyrolysis process was detected with the tunable
      synchrotron vacuum ultraviolet (VUV) photoionization and molecular-beam mass
      spectrometry (MBMS). About thirty intermediates are identified from near
      threshold measurements of photoionization mass spectrum and photoionization
      efficiency spectrum. Among them, H2, CO, CH4, CH3OH and C4H8 are the major
      pyrolysis products. The radicals such as methyl, methoxy, propargyl, allyl, C4H5
      and C4H7 are detected. The isomers of pyrolysis products are identified as well,
      i.e., propyne and allene, 1,2,3-butatriene and vinylacetylene, isobutene and 1
      butene, propanal and acetone. Furthermore, the mole fractions of the pyrolysis
      products have been evaluated under various temperatures. Meanwhile, the initial
      formation temperatures of different pyrolysis products can be obtained. This work
      is anticipated to present a new experimental method for pyrolysis study and help
      understand the pyrolysis and combustion chemistry of MTBE and other oxygenated
      fuels.

PMID- 18823100
TI  - Comparison of nitroaldol reaction mechanisms using accurate ab initio
      calculations.
AB  - In the nitroaldol reaction, condensation between a nitroalkane and an aldehyde
      yields a nitroalcohol that can undergo dehydration to yield a nitroalkene. Amine
      functionalized, MCM-41-type mesoporous silica nanosphere (MSN) materials have
      been shown to selectively catalyze this reaction. Gas-phase reaction paths for
      the several competing mechanisms for the nitroaldol reaction have been mapped out
      using second-order perturbation theory (MP2). Improved relative energies were
      determined using singles and doubles coupled cluster theory with perturbative
      triples, CCSD(T). The mechanism in the absence of a catalyst was used to provide
      a baseline against which to assess the impact of the catalyst on both the
      mechanism and the related energetics. Catalyzed mechanisms can either pass
      through a nitroalcohol intermediate as in the classical mechanism or an imine
      intermediate.

PMID- 18823101
TI  - Simplifying the complex 1H NMR spectra of fluorine-substituted benzamides by spin
      system filtering and spin-state selection: multiple-quantum-single-quantum
      correlation.
AB  - The proton NMR spectra of fluorine-substituted benzamides are very complex
      (Figure 1) due to severe overlap of (1)H resonances from the two aromatic rings,
      in addition to several short and long-range scalar couplings experienced by each
      proton. With no detectable scalar couplings between the inter-ring spins, the
      (1)H NMR spectra can be construed as an overlap of spectra from two independent
      phenyl rings. In the present study we demonstrate that it is possible to separate
      the individual spectrum for each aromatic ring by spin system filtering employing
      the multiple-quantum-single-quantum correlation methodology. Furthermore, the two
      spin states of fluorine are utilized to simplify the spectrum corresponding to
      each phenyl ring by the spin-state selection. The demonstrated technique reduces
      spectral complexity by a factor of 4, in addition to permitting the determination
      of long-range couplings of less than 0.2 Hz and the relative signs of
      heteronuclear couplings. The technique also aids the judicious choice of the spin
      selective double-quantum-single-quantum J-resolved experiment to determine the
      long-range homonuclear couplings of smaller magnitudes.

PMID- 18823102
TI  - Pyrolysis of methyl tert-butyl ether (MTBE). 2. Theoretical study of
      decomposition pathways.
AB  - The thermal decomposition pathways of MTBE have been investigated using the G3B3
      method. On the basis of the experimental observation and theoretical calculation,
      the pyrolysis channels are provided, especially for primary pyrolysis reactions.
      The primary decomposition pathways include formation of methanol and isobutene,
      CH4 elimination, H2 elimination and C-H, C-C, C-O bond cleavage reactions. Among
      them, the formation channel of methanol and isobutene is the lowest energy
      pathway, which is in accordance with experimental observation. Furthermore, the
      secondary pyrolysis pathways have been calculated as well, including
      decomposition of tert-butyl radical, isobutene, methanol and acetone. The
      radicals play an important role in the formation of pyrolysis products, for
      example, tert-butyl radical and allyl radical are major precursors for the
      formation of allene and propyne. Although some isomers (isobutene and 1-butene,
      allene and propyne, acetone and propanal) are identified in our experiment, these
      isomerization reaction pathways occur merely at the high temperature due to their
      high activation energies. The theoretical calculation can explain the
      experimental results reported in part 1 and shed further light on the thermal
      decomposition pathways.

PMID- 18823103
TI  - Polyfunctional methodology for improved DFT thermochemical predictions.
AB  - Statistical error distributions for enthalpies of formation as predicted by 18
      different density functionals have been analyzed using a test set of 675
      molecules. Systematic errors, dependent on the number of valence electrons, have
      been identified for some functionals. A simple empirical correction makes a
      significant improvement in the prediction error for these single functionals.
      Linear combinations of enthalpy estimates from different density functionals are
      identified that exploit the error correlations among the functionals and allow
      for further improvements in the accuracy of thermodynamic predictions. A good
      compromise between accuracy and computational efforts is achieved by the BLUE
      (best linear unbiased estimator) combination of three functionals, B3LYP, BLYP,
      and VSXC (polyfunctional 3 or PF3). The PF3 method has a mean absolute deviation
      (MAD) from experiment of 2.4 kcal/mol on the G3 set of 271 molecules. This can be
      compared to the MAD of 4.9 kcal/mol for B3LYP and 1.2 kcal/mol for the more
      costly G3 method. On the larger set of 675 molecules, the MAD for PF3 is 3.0
      kcal/mol. Opportunities for further improvements in the accuracy of this method
      are discussed.

PMID- 18823104
TI  - Information theoretical study of chirality: enantiomers with one and two
      asymmetric centra.
AB  - In this work, the Kullback-Leibler information deficiency is probed as a
      chirality measure. It is argued that the information deficiency, calculated using
      the shape functions of the R and S enantiomers, considering one as reference for
      the other, gives an information theory based expression useful for quantifying
      chirality. The measure is evaluated for five chiral halomethanes possessing one
      asymmetric carbon atom with hydrogen, fluorine, chlorine, bromine, and iodine as
      substituents. To demonstrate the general applicability, a study of two halogen
      substituted ethanes possessing two asymmetric carbon atoms has been included as
      well. The basic expression of the sum of the local information deficiency over
      all atoms can be decomposed into separate summations over coinciding and
      noncoinciding atoms, or into a global and a mixing entropy term, or into a local
      entropy contribution for each atom individually based on the Hirshfeld
      partitioning. Avnir's continuous chirality measure (CCM) has been computed and
      confronted with the information deficiency. Finally, the relationship between
      chirality and optical rotation is used to study the proposed measure. The results
      illustrate Mezey's holographic electron density theorem with an intuitively
      appealing division of the strength of propagation of the atomic chirality from an
      asymmetric carbon atom throughout the molecule. The local information deficiency
      of the carbon atom is proposed as a measure of chirality; more precisely, the
      difference in information between the R and the S enantiomer turns out to be a
      quantitative measure of the chirality of the system. It may be evaluated as the
      arithmetic mean of the different alignments, or considering only the alignment
      resulting in the highest similarity value, or using the QSSA alignment.

PMID- 18823105
TI  - Parametric investigation of laser-induced fluorescence of solid-state uranyl
      compounds.
AB  - The combination of remote/standoff sensing and laser-induced fluorescence (LIF)
      spectroscopy shows potential for detection of uranyl (UO2(2+)) compounds. Uranyl
      compounds exhibit characteristic emission in the 450-600 nm (22,200 to 16,700 cm(
      1)) spectral region when excited by wavelengths in the ultraviolet or in the
      short-wavelength portion of the visible spectrum. We report a parametric study of
      the effects of excitation wavelength [including 532 nm (18,797 cm(-1)), 355 nm
      (28,169 cm(-1)), and 266 nm (37,594 cm(-1))] and excitation laser power on solid
      state uranium compounds. The uranium compounds investigated include uranyl
      nitrate, uranyl sulfate, uranyl oxalate, uranium dioxide, triuranium octaoxide,
      uranyl acetate, uranyl formate, zinc uranyl acetate, and uranyl phosphate. We
      observed the characteristic uranyl fluorescence spectrum from the uranium
      compounds except for uranium oxide compounds (which do not contain the uranyl
      moiety) and for uranyl formate, which has a low fluorescence quantum yield.
      Relative uranyl fluorescence intensity is greatest for 355 nm excitation, and the
      order of decreasing fluorescence intensity with excitation wavelength (relative
      intensity/laser output) is 355 nm > 266 nm > 532 nm. For 532 nm excitation, the
      emission spectrum is produced by two-photon excitation. Uranyl fluorescence
      intensity increases linearly with increasing laser power, but the rate of
      fluorescence intensity increase is different for different emission bands.

PMID- 18823106
TI  - Electron transfer in the P450cam/PDX complex. The QM/MM e-pathway.
AB  - Electron transfer processes are simple but crucial reactions in biochemistry,
      being one of the main steps in almost all enzymatic cycles. Obtaining an atomic
      description of the transfer pathway is a difficult task, at both the experimental
      and theoretical levels. Here we combine protein-protein docking algorithms,
      protein structure prediction methodologies and mixed quantum mechanics/molecular
      mechanics techniques to map the electron transfer pathway between cytochrome P450
      camphor and its redox partner, putidaredoxin. Although the mechanism of
      interaction and electron transfer for this redox couple has been under
      investigation for over 30 years, the exact mechanism and electron transfer
      pathway has not been fully understood, yet. Our results report the first ab
      initio quantum chemistry description of the electron migration. The obtained
      electron transfer pathway indicates the key role of Arg112 of P450 and Asp38 of
      PDX and the existence of slightly different electron transfer pathways for
      different protein-protein complexes.

PMID- 18823107
TI  - Collisionally assisted spectroscopy of water from 27,000 to 34,000 cm(-1).
AB  - We report here an experimental approach that enables measurement of weak
      transitions to a wide range of rovibrational levels of water in the energy region
      27,000-34,200 cm(-1). We have previously demonstrated the use of laser double
      resonance overtone excitation to access highly excited vibrational levels from
      single rovibrational states. Although this approach simplifies the assignment of
      the spectra, it strongly reduces the number of observed transitions and hence our
      ability to test theoretical predictions. Here, we increase significantly the
      number of observed transitions by allowing rotational relaxation of H2O at
      intermediate levels of the double-resonance excitation scheme to the levels of
      the same nuclear spin (ortho or para). Our recently developed semiempirical
      potential energy surface PES12 enables assignment of the resulting complex
      spectra and reproduction of the measured transitions with accuracy better than 1
      cm(-1).

PMID- 18823108
TI  - Ultrasensitive absorption spectroscopy of optically-trapped aerosol droplets.
AB  - High-sensitivity optical absorption measurements on individual sub-picoliter
      aqueous droplets are reported using aerosol optical tweezers to simultaneously
      manipulate and characterize a sample droplet and a control droplet for
      comparison. It is demonstrated that the detection sensitivity to trace analytes
      is set by the weak absorption by the solvent, water, and that absorbances less
      than 5 x 10(-7) can be measured over pathlengths of less than 10 microm. The
      potential applications of this approach to analyze aerosol particle composition
      and to perform trace analysis are discussed.

PMID- 18823109
TI  - DFT-UX3LYP studies on the coordination chemistry of Ni2+. Part 1: Six coordinate
      [Ni(NH3)n(H2O)(6-n)]2+ complexes.
AB  - DFT calculations with the UX3LYP hybrid functional and a medium-sized 6
      311++G(d,p) basis set were performed to examine the gas-phase structure of
      paramagnetic (S = 1) six-coordinate complexes [Ni(NH3)n(H2O)(6-n)](2+), 0 < or =
      n < or = 6. Significant interligand hydrogen bonding was found in [Ni(H2O)6](2+),
      but this becomes much less significant as NH3 replaces H2O in the coordination
      sphere of the metal. Bond angles and bond lengths obtained from these
      calculations compare reasonably well with available crystallographic data. The
      mean calculated Ni-O bond length in [Ni(H2O)6](2+) is 2.093 A, which is 0.038 A
      longer than the mean of the crystallographically observed values (2.056(22) A,
      108 structures) but within 2sigma of the experimental values. The mean calculated
      Ni-N bond length in [Ni(NH3)6](2+) is 2.205(3) A, also longer (by 0.070 A) than
      the crystallographically observed mean (2.135(18) A, 7 structures). Valence bond
      angles are reproduced within 1 degree. The successive replacement of H2O by NH3
      as ligands results in an increase in the stabilization energy by 7 +/- 2 kcal
      mol(-1) per additional NH3 ligand. The experimentally observed increase in the
      lability of H2O in Ni(II) as NH3 replaces H2O in the coordination sphere is
      explained by an increase in the Ni-OH2 bond length. It was found from a natural
      population analysis that complexes with the highest stabilization energies are
      associated with the greatest extent of ligand-to-metal charge transfer, and the
      transferred electron density is largely accommodated in the metal 4s and 3d
      orbitals. An examination of the charge density rho bcp and the Laplacian of the
      charge density nabla(2)rho(bcp) at the metal-ligand bond critical points (bcp) in
      the series show a linear correlation with the charge transferred to the metal.
      Values of nabla(2)rho(bcp) are positive, indicative of a predominantly closed
      shell interaction. The charge transferred to the metal increases as n, the number
      of NH3 ligands in the complex, increases. This lowers the polarizing ability of
      the metal on the ligand donors and the average metal-ligand bond length
      increases, resulting in a direct correlation between the dissociation energy of
      the complexes and the reciprocal of the average metal-ligand bond length. There
      is a strong correlation between the charge transferred to the metal and
      experimental DeltaH values for successive replacement of H2O by NH3, but a
      correlation with stability constants (log beta values) breaks when n = 5 and 6,
      probably because of entropic effects in solution. Nevertheless, DFT calculations
      may be a useful way of estimating the stability constants of metal-ligand
      systems.

PMID- 18823111
TI  - Axial ligand coordination in sterically strained vanadyl porphyrins: synthesis,
      structure, and properties.
AB  - A hitherto unknown family of six-coordinate vanadyl porphyrins of the sterically
      crowded, nonplanar 2,3,7,8,12,13,17,18-octaethyl-5,10,15,20-tetranitroporphyrin
      incorporating axial ligand L [where L is pyridine, tetrahydrofuran (THF), or
      methanol (MeOH)] has been isolated as VO(tn-OEP)(L) in the solid phase for the
      first time and also structurally characterized. The presence of four electron
      withdrawing, bulky nitro groups at the meso positions of vanadyl
      octaethylporphyrins severely distorts the porphyrin macrocycles and significantly
      enhances the affinity for the axial ligands, where even weak sigma-donating
      ligands, such as MeOH, bind strongly enough to be isolable in the solid phase and
      that too under the offset effects of the macrocyclic distortions. Thus, the axial
      ligand affinity is influenced by both the electronic and conformational effect,
      which cannot be separated completely in this series. The solid-state magnetic
      measurements and their typical electron paramagnetic resonance (EPR) spectrum
      show the presence of a single, unpaired electron, consistent with V(IV)
      formulation. The VO stretching frequency for VO(tn-OEP) occurs as a sharp, strong
      peak at 1008 cm(-1), which is consistent with five-coordinate vanadyl porphyrins,
      while VO(tn-OEP)(L) displays a strong band at lower wavenumbers. The downshift in
      nu(VO) upon axial coordination increases with increasing donor strength of the
      axial ligands; for pyridine, the downshift is 30 cm(-1), while for THF and MeOH,
      the downshifts are nearly 18 cm(-1). X-ray structure determinations authenticate
      axial coordination in a purely saddle-distorted porphyrin macrocycle for all of
      the complexes reported here in which V-Np distances are significantly shorter,
      while the porphyrin cores have been expanded on axial ligand coordination. As a
      result, vanadium atoms are more inplane than in a five-coordinate species. The
      binding of L does not change the spin or metal oxidation states (V(IV), d(1)
      system) of the complexes; therefore, the changes observed are truly the
      reflections of axial ligand coordination. Electrochemical data obtained from
      cyclic voltammetric studies reveal that the complexes are much easier to reduce
      (by approximately 1200 mV) but more difficult to oxidize (by approximately 500
      mV) as compared to nearly planar VO(OEP). The complexes undergo two one-electron
      oxidations due to pi-cation radical and dication formation and three one-electron
      reductions. The first two reductions are because of pi-anion radical and dianion
      formation, while the third quasi-reversible reduction is assigned to a metal
      centered process (V(IV) --> V(III)). These results can be useful for identifying
      the interaction of the vanadyl porphyrins with the biological targets in their
      reported involvement in potent insulinomimetic activity and in anti-HIV agents.

PMID- 18823112
TI  - Mononuclear and binuclear rhenium carbonyl nitrosyls: comparison with their
      manganese analogues.
AB  - The structures and energetics of Re(NO)(CO)n (n = 5, 4, 3, 2) and Re2(NO)2(CO)n
      (n = 7, 6) have been investigated using density functional theory. For
      Re(NO)(CO)4 the preferred structure is an equatorially substituted trigonal
      bipyramid analogous to the known structure of the manganese analogue. The lowest
      energy structures for the unsaturated Re(NO)(CO)n (n = 3, 2) species can be
      derived from this structure by removal of carbonyl groups. A structure is found
      for Re(NO)(CO)5 in which the NO ligand has attached to one of the CO ligands by
      forming a C-N bond to give an unprecedented eta(2)-OCNO ligand. However, this
      structure is predicted to undergo exothermic CO loss to give Re(NO)(CO)4. The
      preferred structures for the binuclear derivatives Re2(NO)2(CO)n (n = 7, 6) are
      structures unprecedented for the manganese analogues and consist of a Re(CO)5
      unit linked to a Re(NO)2(CO)(n-5) unit. However, only slightly higher in energy
      are structures of the type Re2(mu-NO)2(CO)n with two bridging nitrosyl groups,
      similar to the global minima for the manganese analogues. These results predict
      extensive areas of new rhenium carbonyl nitrosyl chemistry. Thus the synthesis of
      Re(NO)(CO)4 by methods related to the synthesis of the manganese analogue appears
      to be feasible. In addition, the existence of an extensive series of
      Re(NO)2(CO)2X derivatives, as well as a Re2(NO)4(CO)4 dimer, is predicted.

PMID- 18823110
TI  - A copper(I)-catalyzed 1,2,3-triazole azide-alkyne click compound is a potent
      inhibitor of a multidrug-resistant HIV-1 protease variant.
AB  - Treatment with HIV-1 protease inhibitors, a component of highly active
      antiretroviral therapy (HAART), often results in viral resistance. Structural and
      biochemical characterization of a 6X protease mutant arising from in vitro
      selection with compound 1, a C 2-symmetric diol protease inhibitor, has been
      previously described. We now show that compound 2, a copper(I)-catalyzed 1,2,3
      triazole derived compound previously shown to be potently effective against wild
      type protease (IC 50 = 6.0 nM), has low nM activity (IC 50 = 15.7 nM) against the
      multidrug-resistant 6X protease mutant. Compound 2 displays similar efficacy
      against wild-type and 6X HIV-1 in viral replication assays. While structural
      studies of compound 1 bound to wild type and mutant proteases revealed a
      progressive change in binding mode in the mutants, the 1.3 A resolution 6X
      protease-compound 2 crystal structure reveals nearly identical interactions for 2
      as in the wild-type protease complex with very little change in compound 2 or
      protease conformation.

PMID- 18823113
TI  - Computational study of iron bis(dithiolene) complexes: redox non-innocent ligands
      and antiferromagnetic coupling.
AB  - The molecular and electronic structure of monomeric ([Fe(S2C2H2)2](z),
      [Fe(S2C2(C6H4-p-OCH3)2)2](z)) and dimeric ([{Fe(S2C2H2)2}2](z)) iron
      bis(dithiolene) complexes, and of their phosphine adducts ([(PH3)Fe(S2C2H2)2](z),
      [(P(C6H5)3)Fe(S2C2H2)2](z), [(PH3)Fe(S2C2(C6H4-p-OCH3)2)2](z)), carrying various
      charges (z = 0, 1-, 2-), have been investigated by density functional theory
      (DFT). Net total spin polarization values S of zero, two, and four have been
      considered for all neutral model compounds and their dianions, whereas all
      monoanions have been examined with net total spin polarization values S of one,
      three, and five. The DFT calculations utilized the pure functional BP86, as well
      as the hybrid functionals B3LYP and B3LYP*. For the monomers, the calculations
      reveal the presence of redox non-innocent dithiolene ligands and
      antiferromagnetic coupling between the ligands and the metal center. For the
      dimers, complexes with antiferromagnetically coupled iron centers have been found
      to represent structures of low energy, if not lowest energy structures. The spin
      coupling constant of [{Fe(S2C2H2)2}2](2-) is calculated as J = -230 cm(-1). On
      the basis of the computational results, a model for reversible, electrochemically
      controlled binding and release of phosphine ligands to iron bis(dithiolene)
      complexes is proposed. Only BP86 and B3LYP* results, but not those of B3LYP
      calculations, are in qualitative agreement with experimental findings. BP86
      calculations provide the best quantitative match in comparison with the
      experiment.

PMID- 18823114
TI  - A unique Mn2Gd2 tetranuclear compound of p-tert-butylthiacalix[4]arene.
AB  - A calixarene complex with tetragonal Mn(II 2Gd(III)2 tetranuclear units was
      synthesized in solvothermal conditions, where the addition of a small amount of
      water was crucial for the formation of the target compound. In the structure, two
      tail-to-tail p-tert-butylthiacalixarenes are located in a C-shaped mode with a
      dihedral angle of 14.29 degrees but not in the conventional antiparallel
      arrangement and form a sandwich-like subunit with an in-between Mn2Gd2 unit. Both
      calixarenes assume similar cone shapes of C2v symmetry but are pinched to
      different extents. The extended structure is constructed by supramolecular
      stacking of the sandwich-like units with the interstices filled by the solvent.
      The magnetic property of the title compound has been examined.

PMID- 18823115
TI  - Persistent radicals of trivalent tin and lead.
AB  - In this report we present synthetic, crystallographic, and new electron
      paramagnetic resonance (EPR) spectroscopic work that shows that the synthetic
      route leading to the recently reported, first persistent plumbyl radical *PbEbt3
      (Ebt = ethylbis(trimethylsilyl)silyl), that is, the oxidation of the related
      PbEbt3-anion, was easily extended to the synthesis of other persistent molecular
      mononuclear radicals of lead and tin. At first, various novel solvates of
      homoleptic potassium metallates KSnHyp3 (4a), KPbHyp3 (3a), KSnEbt3 (4b), KPbIbt3
      (3c), and KSnIbt3 (4c) (Hyp = tris(trimethylsilyl)silyl, Ibt =
      isopropylbis(trimethylsilyl)silyl), as well as some heteroleptic metallates, such
      as [Li(OEt2)2][Sn(n)BuHyp2] (3d), [Li(OEt2)2][Pb(n)BuHyp2] (4d),
      [Li(thf)4][PbPhHyp2] (3e), and [K(thf)7][PbHyp2{N(SiMe3)2}] (3f), were
      synthesized and crystallographically characterized. Through oxidation by tin(II)
      and lead(II) bis(trimethylsilyl)amides or the related 2,6-di-tert
      butylphenoxides, they had been oxidized to yield in most cases the corresponding
      radicals. Five novel persistent homoleptically substituted radicals, that is,
      *SnHyp3 (2a), *PbHyp3 (1a), *SnEbt3 (2b), *SnIbt3 (2c), and *PbIbt3 (1c), had
      been characterized by EPR spectroscopy. The stannyl radicals 2a and 2c as well as
      the plumbyl radical 1c were isolated as intensely colored crystalline compounds
      and had been characterized by X-ray diffraction. Persistent heteroleptically
      substituted radicals such as *PbHyp2Ph (1e) or *PbHyp2Et (1g) had also been
      generated, and some selected EPR data are given for comparison. The plumbyl
      radicals *PbR3 exhibit a clean monomolecular decay leading to the release of a
      temperature-dependent stationary concentration of branched silyl radicals. They
      may thus serve as tunable sources of these reactive species that may be utilized
      as reagents for mild radical silylations and/or as initiators for radical
      polymerizations. We present EPR-spectroscopic investigations for the new tin- and
      lead-containing compounds giving detailed insights into their electronic and
      geometric structure in solution, as well as structural studies on the crystalline
      state of the radicals, some of their anionic precursors, and some side-products.

PMID- 18823116
TI  - Water at the surfaces of aligned phospholipid multibilayer model membranes probed
      with ultrafast vibrational spectroscopy.
AB  - The dynamics of water at the surface of artificial membranes composed of aligned
      multibilayers of the phospholipid dilauroyl phosphatidylcholine (DLPC) are probed
      with ultrafast polarization selective vibrational pump-probe spectroscopy. The
      experiments are performed at various hydration levels, x = 2 - 16 water molecules
      per lipid at 37 degrees C. The water molecules are approximately 1 nm above or
      below the membrane surface. The experiments are conducted on the OD stretching
      mode of dilute HOD in H 2O to eliminate vibrational excitation transfer. The FT
      IR absorption spectra of the OD stretch in the DLPC bilayer system at low
      hydration levels shows a red-shift in frequency relative to bulk water, which is
      in contrast to the blue-shift often observed in systems such as water nanopools
      in reverse micelles. The spectra for x = 4 - 16 can be reproduced by a
      superposition of the spectra for x = 2 and bulk water. IR Pump-probe measurements
      reveal that the vibrational population decays (lifetimes) become longer as the
      hydration level is decreased. The population decays are fit well by biexponential
      functions. The population decays, measured as a function of the OD stretch
      frequency, suggest the existence of two major types of water molecules in the
      interfacial region of the lipid bilayers. One component may be a clathrate-like
      water cluster near the hydrophobic choline group and the other may be related to
      the hydration water molecules mainly associated with the phosphate group. As the
      hydration level increases, the vibrational lifetimes of these two components
      decrease, suggesting a continuous evolution of the hydration structures in the
      two components associated with the swelling of the bilayers. The agreement of the
      magnitudes of the two components obtained from IR spectra with those from
      vibrational lifetime measurements further supports the two-component model. The
      vibrational population decay fitting also gives an estimation of the number of
      phosphate-associated water molecules and choline-associated water molecules,
      which range from 1 to 4 and 1 to 12, respectively, as x increases from 2 to 16.
      Time-dependent anisotropy measurements yield the rate of orientational relaxation
      as a function of x. The anisotropy decay is biexponential. The fast component is
      almost independent of x, and is interpreted as small orientational fluctuations
      that occur without hydrogen-bond rearrangement. The slower component becomes very
      long as the hydration level decreases. This component is a measure of the rate of
      complete orientational randomization, which requires H-bond rearrangement and is
      discussed in terms of a jump reorientation model.

PMID- 18823117
TI  - Chirality-controlled and solvent-templated catenation isomerism in metal-organic
      frameworks.
AB  - A family of highly porous homochiral, racemic, and meso metal-organic frameworks
      (MOFs) were synthesized based on a new elongated tetra-carboxylate ligand and the
      copper paddle-wheel building units. These MOFs exhibited remarkable catenation
      isomerism that is controlled by both chirality of the bridging ligand and the
      size of solvent molecules. The ability to manipulate framework interpenetration
      is key to future synthesis of mesoporous homochiral MOFs which hold great promise
      in heterogeneous asymmetric catalysis and chiral separations.

PMID- 18823118
TI  - Dynamic allosteric control of noncovalent DNA catalysis reactions.
AB  - Allosteric modulation of catalysis kinetics is prevalent in proteins and has been
      rationally designed for ribozymes. Here, we present an allosteric DNA molecule
      that, in its active configuration, catalyzes a noncovalent DNA reaction. The
      catalytic activity is designed to be modulated by the relative concentrations of
      two DNA regulator molecules, one an inhibitor and the other an activator. Dynamic
      control of the catalysis rate is experimentally demonstrated via three cycles of
      up and down regulation by a factor of over 10. Unlike previous works, both the
      allosteric receptor and catalytic core are designed, rather than evolved. This
      allows flexibility in the sequence design and modularity in synthetic network
      construction.

PMID- 18823119
TI  - Sequence- and chain-length-specific complementary double-helix formation.
AB  - The artificial sequential strands consisting of two, three, or four m-terphenyl
      groups joined by diacetylene linkers with complementary binding sites, either the
      chiral amidine (A) or achiral carboxyl (C) group, were synthesized in a stepwise
      manner. Using circular dichroism and (1)H NMR spectroscopies along with liquid
      chromatography, we showed that, when three dimeric molecular strands (AA, CC, and
      AC) or six trimeric molecular strands (AAA, CCC, AAC, CCA, ACA, and CAC) were
      mixed in solution, the complementary strands were sequence-specifically
      hybridized to form one-handed double-helical dimers AA.CC and (AC) 2 or trimers
      AAA.CCC, AAC.CCA, and ACA.CAC, respectively, through complementary amidinium
      carboxylate salt bridges. Upon the addition of CCA to a mixture of AAA, AAC, and
      ACA, the AAC.CCA double helix was selectively formed and then isolated from the
      mixture by chromatography. Moreover, the homo-oligomer mixtures of amidine or
      carboxylic acid from the monomers to tetramers (A, AA, AAAA, C, CC, and CCCC)
      assembled with a precise chain length specificity to form A.C, AA.CC, and
      AAAA.CCCC, which were separated by chromatography.

PMID- 18823120
TI  - Synthesis and electronic properties of conjugated pentacene dimers.
AB  - Conjugated pentacene dimers 1-3 were synthesized in two steps from readily
      available precursors. Noteworthy is the initial step, which assembles five
      independent fragments to form the carbon-rich molecular framework. Solution-cast
      films of these materials are air stable. Photocurrent measurements for solution
      deposited thin films show that dimer 3 exhibits photoconductive gain >10.

PMID- 18823121
TI  - Versatile synthesis of head group functionalized phospholipids via oxime bond
      formation.
AB  - A method for introduction of various head groups on phospholipid frameworks via
      oxime bond formation has been developed for the synthesis of cyclen-Cu(II),
      pyrene, naphthalene, and other headgroup functionalized phospholipids that can
      cleave the membrane protein, hemagglutinin.

PMID- 18823122
TI  - Mono- and penta-addition of enol silyl ethers to [60]fullerene.
AB  - The reaction of 1-alkoxy-1-siloxyethene with [60]fullerene in 20%
      DMSO/chlorobenzene at ambient temperature under an oxygen atmosphere gave a penta
      addition product, while the reaction of 1-alkoxy-1-siloxyalkenes or 1,2
      siloxyalkenes under argon gave monoaddition products. The new method has merits
      over the previously reported syntheses of these compounds in that the synthesis
      does not require the use of heavy metals or photolysis conditions, and it can be
      carried out under simple and mild conditions.

PMID- 18823123
TI  - Prediction of a new pathway to presilphiperfolanol.
AB  - Quantum chemical calculations on the conversion of farnesyl diphosphate to
      presilphiperfolanol are described. On the basis of the results of this
      theoretical study, we predict a new mechanism for presilphiperfolanol formation
      that involves the intermediacy of nerolidyl diphosphate and an unusual reaction
      step in which a 1,2-alkyl shift and a transannular alkene attack are combined
      into a concerted process.

PMID- 18823124
TI  - Highly acylated (acetylated and/or p-coumaroylated) native lignins from diverse
      herbaceous plants.
AB  - The structure of lignins isolated from the herbaceous plants sisal ( Agave
      sisalana), kenaf ( Hibiscus cannabinus), abaca ( Musa textilis) and curaua (
      Ananas erectifolius) has been studied upon spectroscopic (2D-NMR) and chemical
      degradative (derivatization followed by reductive cleavage) methods. The analyses
      demonstrate that the structure of the lignins from these plants is highly
      remarkable, being extensively acylated at the gamma-carbon of the lignin side
      chain (up to 80% acylation) with acetate and/or p-coumarate groups and
      preferentially over syringyl units. Whereas the lignins from sisal and kenaf are
      gamma-acylated exclusively with acetate groups, the lignins from abaca and curaua
      are esterified with acetate and p-coumarate groups. The structures of all these
      highly acylated lignins are characterized by a very high syringyl/guaiacyl ratio,
      a large predominance of beta- O-4' linkages (up to 94% of all linkages), and a
      strikingly low proportion of traditional beta-beta' linkages, which indeed are
      completely absent in the lignins from abaca and curaua. The occurrence of beta
      beta' homocoupling and cross-coupling products of sinapyl acetate in the lignins
      from sisal and kenaf indicates that sinapyl alcohol is acetylated at the monomer
      stage and that, therefore, sinapyl acetate should be considered as a real
      monolignol involved in the lignification reactions.

PMID- 18823125
TI  - Effect of plasticizer type and amount on hydroxypropyl methylcellulose-beeswax
      edible film properties and postharvest quality of coated plums (cv. Angeleno).
AB  - The effect of the composition of hydroxypropyl methylcellulose (HPMC)-beeswax
      (BW) edible coatings on stand-alone film properties and on postharvest quality of
      coated 'Angeleno' plums was studied. Glycerol (G) and mannitol (M) were tested as
      plasticizers at two different plasticizer/HPMC ratios (100:1 and 300:1 molar
      basis). BW content was 20 or 40% (dry basis). An increase in G content increased
      film flexibility and vapor permeability (WVP), whereas an increase in M content
      enhanced film brittleness without affecting WVP. An increase in BW content
      reduced film flexibility and reduced WVP of only G-plasticized films. Coatings
      reduced plum softening and bleeding, but were not effective in reducing plum
      weight loss. At low plasticizer content, coatings reduced texture loss
      effectively. Low BW also lowered plum bleeding. Plasticizer type affected only
      ethanol and acetaldehyde contents without affecting the remaining quality
      parameters. Therefore, HPMC-BW coatings have the potential to extend the shelf
      life of plums. However, this effect depends on coating composition. Differences
      between coating and film performance indicate that data from stand-alone films
      may be used as a preliminary screening, but coating performance should be
      analyzed on coated fruit.

PMID- 18823126
TI  - Regulation of sterol transport between membranes and NPC2.
AB  - Niemann-Pick disease type C (NPC) is caused by defects in either the NPC1 or NPC2
      gene and is characterized by accumulation of cholesterol and glycolipids in the
      late endosome/lysosome compartment. NPC2 is an intralysosomal protein that binds
      cholesterol in vitro. Previous studies demonstrated rapid rates of cholesterol
      transfer from NPC2 to model membranes [Cheruku, S. R., et al. (2006) J. Biol.
      Chem. 281, 31594-31604]. To model the potential role of NPC2 as a lysosomal
      cholesterol export protein, in this study we used fluorescence spectroscopic
      approaches to examine cholesterol transfer from membranes to NPC2, assessing the
      rate, mechanism, and regulation of this transport step. In addition, we examined
      the effect of NPC2 on the rate and kinetic mechanism of intermembrane sterol
      transport, to model the movement of cholesterol from internal lysosomal membranes
      to the limiting lysosomal membrane. The results support the hypothesis that NPC2
      plays an important role in endo/lysosomal cholesterol trafficking by markedly
      accelerating the rates of cholesterol transport. Rates of sterol transfer from
      and between membranes were increased by as much as 2 orders of magnitude by NPC2.
      The transfer studies indicate that the mechanism of NPC2 action involves direct
      interaction of the protein with membranes. Such interactions were observed
      directly using FTIR spectroscopy and protein tryptophan spectral shifts.
      Additionally, cholesterol transfer by NPC2 was found to be greatly enhanced by
      the unique lysosomal phospholipid lyso-bisphosphatidic acid (LBPA), suggesting an
      important role for LBPA in NPC2-mediated cholesterol trafficking.

PMID- 18823127
TI  - Weak coupling of ATP hydrolysis to the chemical equilibrium of human nicotinamide
      phosphoribosyltransferase.
AB  - Human nicotinamide phosphoribosyltransferase (NAMPT, EC 2.4.2.12) catalyzes the
      reversible synthesis of nicotinamide mononucleotide (NMN) and inorganic
      pyrophosphate (PP i) from nicotinamide (NAM) and alpha- d-5-phosphoribosyl-1
      pyrophosphate (PRPP). NAMPT, by capturing the energy provided by its facultative
      ATPase activity, allows the production of NMN at product:substrate ratios
      thermodynamically forbidden in the absence of ATP. With ATP hydrolysis coupled to
      NMN synthesis, the catalytic efficiency of the system is improved 1100-fold,
      substrate affinity dramatically increases ( K m (NAM) from 855 to 5 nM), and the
      K eq shifts -2.1 kcal/mol toward NMN formation. ADP-ATP isotopic exchange
      experiments support the formation of a high-energy phosphorylated intermediate
      (phospho-H247) as the mechanism for altered catalytic efficiency during ATP
      hydrolysis. NAMPT captures only a small portion of the energy generated by ATP
      hydrolysis to shift the dynamic chemical equilibrium. Although the weak energetic
      coupling of ATP hydrolysis appears to be a nonoptimized enzymatic function,
      closer analysis of this remarkable protein reveals an enzyme designed to capture
      NAM with high efficiency at the expense of ATP hydrolysis. NMN is a rate-limiting
      precursor for recycling to the essential regulatory cofactor, nicotinamide
      adenine dinucleotide (NAD (+)). NMN synthesis by NAMPT is powerfully inhibited by
      both NAD (+) ( K i = 0.14 muM) and NADH ( K i = 0.22 muM), an apparent regulatory
      feedback mechanism.

PMID- 18823128
TI  - Association properties of betaB1- and betaA3-crystallins: ability to form
      heterotetramers.
AB  - As major constituents of the mammalian lens, beta-crystallins associate into
      dimers, tetramers, and higher-order complexes to maintain lens transparency and
      refractivity. A previous study has shown that dimerization of betaB2- and betaA3
      crystallins is energetically highly favored and entropically driven. While
      heterodimers further associate into higher-order complexes in vivo, a significant
      level of reversibly associated tetrameric crystallin has not been previously
      observed in vitro. To enhance our understanding of the interactions between beta
      crystallins, we characterized the association of betaB1-crystallin, a major
      component of large beta-crystallin complexes (beta-high), with itself and with
      betaA3-crystallin. Mouse betaB1-crystallin and human betaA3-crystallin were
      expressed in Escherichia coli and purified chromatographically. Their association
      was then characterized using size-exclusion chromatography, native gel
      electrophoresis, isoelectric focusing, and analytical sedimentation equilibrium
      centrifugation. When present alone, each beta-crystallin associates into
      homodimers; however, no tetramer formation is seen. Once mixing has taken place,
      formation of a heterocomplex between betaB1- and betaA3-crystallins is observed
      using size-exclusion chromatography, native gel electrophoresis, isoelectric
      focusing, and sedimentation equilibrium. In contrast to results previously
      obtained after betaB2- and betaA3-crystallins had been mixed, mixed betaB1- and
      betaA3-crystallins show a dimer-tetramer equilibrium with a K d of 1.1 muM,
      indicating that these two beta-crystallins associate predominantly into
      heterotetramers in vitro. Thus, while each purified beta-crystallin associates
      only into homodimers and under the conditions studied mixed betaB2- and betaA3
      crystallins form a mixture of homo- and heterodimers, mixed betaB1- and betaA3
      crystallins associate predominantly into heterotetramers in equilibrium with
      heterodimers. These findings suggest a unique role for betaB1-crystallin in
      promoting higher-order crystallin association in the lens.

PMID- 18823129
TI  - Energetics of the cleft closing transition and the role of electrostatic
      interactions in conformational rearrangements of the glutamate receptor ligand
      binding domain.
AB  - The ionotropic glutamate receptors are localized in the pre- and postsynaptic
      membrane of neurons in the brain. Activation by the principal excitatory
      neurotransmitter glutamate allows the ligand binding domain to change
      conformation, communicating opening of the channel for ion conduction. The free
      energy of the GluR2 S1S2 ligand binding domain (S1S2) closure transition was
      computed using a combination of thermodynamic integration and umbrella sampling
      modeling methods. A path that involves lowering the charge on E705 was chosen to
      clarify the role of this binding site residue. A continuum electrostatics
      approach in S1S2 is used to show E705, located in the ligand binding cleft,
      stabilizes the closed conformation of S1S2 via direct interactions with other
      protein residues, not through the ligand. In the closed conformation, in the
      absence of a ligand, S1S2 is somewhat more closed than what has been reported in
      X-ray structures. A semiopen conformation has been identified which is
      characterized by disruption of a single cross-cleft interaction and differs only
      slightly in energy from the fully closed S1S2. The fully open S1S2 conformation
      exhibits a wide energy well and shares structural similarity with the apo S1S2
      crystal structure. Hybrid continuum electrostatics/MD calculations along the
      chosen closure transition pathway reveal solvation energies, and electrostatic
      interaction energies between two lobes of the protein increase the relative
      energetic difference between the open and closed conformational states. By
      analyzing the role of several cross-cleft contacts as well as other binding site
      residues, we demonstrate how S1S2 interactions facilitate formation of the closed
      conformation of the GluR2 ligand binding domain.

PMID- 18823130
TI  - Size-controlled, one-pot synthesis, characterization, and biological applications
      of epoxy-organosilica particles possessing positive zeta potential.
AB  - Epoxy-organosilica particles made from 2-(3,4
      epoxycyclohexyl)ethyltrimethoxysilane (EpoMS) as a single silica source were
      synthesized by means of a one-pot method. We evaluated three sets of synthesis
      conditions, including traditional Stober conditions and two variations. Although
      the traditional conditions did not afford EpoMS particles, the variations did.
      The size distributions of the particles were evaluated by means of transmission
      electron microscopy. The mean diameters and size distributions of the particles
      depended on the EpoMS concentration, and the best coefficient of variation for
      the size distribution was 5.9%. The surface of the particles had unique
      properties, such as a positive zeta potential. The particles bound strongly to
      proteins as well as to DNA. The particles made from EpoMS, allowing particles
      internally functionalized with fluorescent dye to be prepared by means of a one
      pot synthesis. EpoMS particles doped and tuned with fluorescent dye showed strong
      fluorescence signals and distinct peaks on flow cytometry, and the fluorescent
      particles could be used to label cells. The labeled cells showed clear
      fluorescence under a fluorescence microscope, and electron microscopy showed many
      particles in the cytoplasm. This is the first report describing the synthesis of
      epoxy-organosilica particles with a positive zeta potential and describing
      differences in the characteristics of particle formations due to changes in
      synthesis conditions. We also discuss the advantages of EpoMS particles, as well
      as the potential biological applications of these particles.

PMID- 18823131
TI  - In situ polymerization of molecular macroclusters on a silica surface: poly(N
      isopropylacrylamide) nanofilms.
AB  - We have found that alcohols, carboxylic acids, and amides self-assemble into a
      unique molecular architecture, a hydrogen-bonded molecular macrocluster, when
      they are selectively adsorbed onto silica (glass and oxidized silicon) surfaces
      in nonpolar solvents such as cyclohexane. In our previous study, this phenomenon
      could be successfully applied to fabricate molecularly flat and defect-free
      nanofilms of several tens of nanometers thickness. In this study, we prepared a
      poly(N-isopropylacrylamide) [poly(NIPAAm)] film on the basis of in situ
      polymerization of a monomer macrocluster layer formed on silica surfaces and
      investigated how the molecular arrangement of the adsorbed NIPAAm monomers
      affects the efficiency of the polymerization of them. Poly(NIPAAm) films were
      prepared by the following two methods: (1) the one-solution method, the in situ
      photopolymerization of an NIPAAm monomer adsorption layer on silica in one
      solution (chloroform, cyclohexane, and toluene), and (2) the solution exchange
      method, adsorption of NIPAAm monomers onto a silica surface from NIPAAm (0.1 mol
      %) in chloroform, exhange of the solution to 0.005 mol % NIPAAm in cyclohexane,
      and then polymerization by UV irradiation. By the solution exchange method,
      molecularly flat, defect-free, and thermoresponsive films were obtained and the
      thickness could be controlled by the irradiation time, while only several
      nanometers thickness could be attained by the one-solution method. The structure
      of NIPAAm adsorption layers formed in each solution condition was characterized
      by attenuated total reflection Fourier transform infrared spectroscopy. It was
      revealed that only the solution exchange procedure induced the beta-sheet-like
      adsorbed structure of NIPAAm in which the double bonds of neighboring NIPAAm
      monomers were closely located, which should have resulted in effective
      polymerization.

PMID- 18823132
TI  - Solvent driven motion of lithographically fabricated gels.
AB  - We investigated the solvent driven motion of lithographically structured poly- N
      isopropylacrylamide (PNIPAm) gels. The gels were soaked in ethanol and then
      transferred to water, where they moved spontaneously. This movement was driven by
      the expulsion of the ethanol from the gel and subsequent ethanol spreading at the
      air-water interface. We utilized lithographic patterning of the gels at the
      micron-millimeter length scales to investigate the effect of size, shape and
      symmetry. Lithographic patterning allowed the structures to be fabricated in an
      identical manner, thereby allowing a single variable (such as shape, size, or
      symmetry) to be altered while minimizing change in other variables such as
      thickness, roughness and swelling characteristics. The diverse range of motions
      including translation, precession and rotation could be controlled and were
      recorded using videography. Gels were lithographically patterned with features
      less than 100 microm, and exhibited remarkably high linear and rotational
      velocities of up to 31 cm/s and 3529 rpm over time spans of seconds to minutes.
      We observed a reciprocal dependence of maximum rotational velocity on linear
      dimension. The linear velocity for all types of motion, along a line or curve,
      was analyzed and found to be similar across different shapes and sizes. This
      velocity was in the range of 17-39 cm/s even though our sizes and shapes varied
      across orders of magnitude. We postulate that this velocity is related to the
      velocity of spreading of ethanol on water, which is approximately 53 cm/s.
      Additionally, since this solvent powered motion is a clean, quiet and reusable
      source of motive power, with no need for on-board wiring or batteries, we
      explored applications in moving lithographically integrated metallic payloads on
      top of the gels and utilized the gels to move larger floating objects.

PMID- 18823133
TI  - Atomic force microscopy reveals hydroxyapatite-citrate interfacial structure at
      the atomic level.
AB  - An approach to organic-inorganic interfacial structure at the atomic level is a
      great challenge in the studies of biomineralization. We demonstrate that atomic
      force microscopy (AFM) is powerful tool to discover the biomineral interface in
      detail. By using a model system of (100) hydroxyapatite (HAP) face and citrate,
      it reveals experimentally that only a side carboxylate and a surface calcium ion
      are involved in the binding effect during the citrate adsorption, which is
      against the previous understandings by using Langmuir adsorption and computer
      simulation. Furthermore, the adsorbed citrate molecules can use their free
      carboxylate and hydroxyl groups to be self-assembled on the HAP surface. AFM
      examination also finds that the presence of citrate molecules on the HAP crystal
      faces can enhance the adhesion force of the HAP surface. We suggest that the
      established AFM method can be used for a precise and direct understanding of
      biointerfaces at the atomic level.

PMID- 18823134
TI  - Colloidal behavior of aluminum oxide nanoparticles as affected by pH and natural
      organic matter.
AB  - The colloidal behavior of aluminum oxide nanoparticles (NPs) was investigated as
      a function of pH and in the presence of two structurally different humic acids
      (HAs), Aldrich HA (AHA) and the seventh HA fraction extracted from Amherst peat
      soil (HA7). Dynamic light scattering (DLS) and atomic force microscopy (AFM) were
      employed to determine the colloidal behavior of the NPs. Influence of pH and HAs
      on the surface charges of the NPs was determined. zeta-Potential data clearly
      showed that the surface charge of the NPs decreased with increasing pH and
      reached the point of zero charge (ZPC) at pH 7.9. Surface charge of the NPs also
      decreased with the addition of HAs. The NPs tend to aggregate as the pH of the
      suspension approaches ZPC, where van der Waals attraction forces dominate over
      electrostatic repulsion. However, the NP colloidal suspension was stable in the
      pHs far from ZPC. Colloidal stability was strongly enhanced in the presence of
      HAs at the pH of ZPC or above it, but in acidic conditions NPs showed strong
      aggregation in the presence of HAs. AFM imaging revealed the presence of long
      chain fractions in HA7, which entangled with the NPs to form large aggregates.
      The association of HA with the NP surface can be assumed to follow a two-step
      process, possibly the polar fractions of the HA7 sorbed on the NP surface
      followed by entanglement with the long-chain fractions. Thus, our study
      demonstrated that the hydrophobic nature of the HA molecules strongly influenced
      the aggregation of colloidal NPs, possibly through their conformational behavior
      in a particular solution condition. Therefore, various organic matter samples
      will result in different colloidal behavior of NPs, subsequently their
      environmental fate and transport.

PMID- 18823135
TI  - Toposelective electrochemical desorption of thiol SAMs from neighboring
      polycrystalline gold surfaces.
AB  - We describe a method for the selective desorption of thiol self-assembled
      monolayers from gold surfaces having micrometer-scale separations on a substrate.
      In an electrolyte solution, the electrical resistance between the adjacent areas
      can be much lower than the resistance between a surface and the counter
      electrode. Also, both reductive and oxidative thiol desorption may occur.
      Therefore, the potentials of the surfaces must be independently controlled with a
      multichannel potentiostat and operating windows for a given thiol/electrolyte
      system must be established. In this study operating windows were established for
      1-dodecanethiol-based SAMs in phosphate buffer, phosphate-buffered saline, and
      sodium hydroxide solution, and selective SAM removal was successfully performed
      in a four-electrode configuration.

PMID- 18823136
TI  - Tunable porosity in bridged organosilicas using self-organizing precursors.
AB  - Functionalized, mesoporous organosilicas with tunable porosity were prepared by a
      direct and simple approach from rationally designed precursors, combining the
      function of a network builder and a porogen in one molecule. The precursors are
      synthesized using a dual hydroboration reaction, fulfilling the criteria of
      "click-chemistry", first on an ethylene-bridged organosilica and then on a long
      chain alkene. Thus, in the final molecule the boron atom connects the sol-gel
      precursor (the bridged organosilica) with the porogen (the long-chain alkene).
      The so-prepared precursors do self-organize when hydrolysis of their inorganic
      moiety takes place via an aggregation of their organic side chains into
      hydrophobic domains. The length of the attached chain influences the size of the
      hydrophobic domain and thus, after a condensation-aminolysis sequence, the
      finally observed porosity of the organosilicas. Depending on chain length micro-
      to mesoporous materials with average pore sizes from 1.5 to 4.1 nm (for attached
      pentene to hexadecene chains) are observed. Furthermore, the boron entity enables
      the subsequent introduction of various functional groups into the pore walls of
      the organosilica networks. Amine or hydroxyl functionalities can be easily
      introduced, dependent on the experimental conditions used during the borane
      cleavage and extraction step. The accessibility of these functionalities can be
      proven by a significant metal adsorption onto the functional organosilica walls.

PMID- 18823137
TI  - Time-dependent interactions of the two porphyrinic compounds chlorin e6 and mono
      L-aspartyl-chlorin e6 with phospholipid vesicles probed by NMR spectroscopy.
AB  - The distribution processes of chlorin e6 (CE) and monoaspartyl-chlorin e6 (MACE)
      between the outer and inner phospholipid monolayers of 1,2-dioleoyl
      phosphatidylcholine (DOPC) vesicles were monitored by 1H NMR spectroscopy through
      analysis of chemical shifts and line widths of the DOPC vesicle resonances.
      Chlorin adsorption to the outer vesicle monolayer induced changes in the DOPC 1H
      NMR spectrum. Most pronounced was a split of the N-methyl choline resonance,
      allowing for separate analysis of inner and outer vesicle layers. Transbilayer
      distribution of the chlorin compounds was indicated by time-dependent
      characteristic spectral changes of the DOPC resonances. Kinetic parameters for
      the flip-flop processes, that is, half-lives and rate constants, were obtained
      from the experimental data points. In comparison to CE, MACE transbilayer
      movement was significantly reduced, with MACE remaining more or less attached to
      the outer membrane layer. The distribution coefficients for CE and MACE between
      the vesicular and aqueous phase were determined. Both CE and MACE exhibited a
      high affinity for the vesicular phase. For CE, a positive correlation was found
      between transfer rate and increasing molar ratio CE/DOPC. Enhanced membrane
      rigidity induced by increasing amounts of cholesterol into the model membrane was
      accompanied by a decrease of CE flip-flop rates across the membrane. The present
      study shows that the movement of porphyrins across membranes can efficiently be
      investigated by 1H NMR spectroscopy and that small changes in porphyrin structure
      can have large effects on membrane kinetics.

PMID- 18823138
TI  - X-ray reflectivity measurements of layer-by-layer films at the solid/liquid
      interface.
AB  - In this Letter, we present a method for the decoration of layer-by-layer (LbL)
      structures by heavy metal ions, which allows X-ray reflectivity (XRR)
      measurements at the solid/water interface. The improved contrast has allowed us
      to obtain well-structured X-ray reflectivity curves from samples at the
      liquid/solid interface that can be used for the film structure modeling. The
      developed technique was also used to follow the formation of complexes between
      DNA and the LbL multilayer. The XRR data are confirmed by independent null
      ellipsometric measurements at the solid/liquid interface on the very same
      architectures.

PMID- 18823139
TI  - Comparative proteomic analysis provides new insights into the fiber elongating
      process in cotton.
AB  - A comparative proteomic analysis was performed to explore the mechanism of cell
      elongation in developing cotton fibers. The temporal changes of global proteomes
      at five representative development stages (5-25 days post-anthesis [dpa]) were
      examined using 2-D electrophoresis. Among approximately 1800 stained protein
      spots reproducibly detected on each gel, 235 spots were differentially expressed
      with significant dynamics in elongating fibers. Of these, 120 spots showed a more
      than 2-fold change in at least one stage point, and 21 spots appeared to be
      specific to developmental stages. Furthermore, 106 differentially expressed
      proteins were identified from mass spectrometry to match 66 unique protein
      species. These proteins involve different cellular and metabolic processes with
      obvious functional tendencies toward energy/carbohydrate metabolism, protein
      turnover, cytoskeleton dynamics, cellular responses and redox homeostasis,
      indicating a good correlation between development-dependent proteins and fiber
      biochemical processes, as well as morphogenesis. Newly identified proteins such
      as phospholipase D alpha, vf14-3-3 protein, small ras-related protein, and GDP
      dissociation inhibitor will advance our knowledge of the complicated regulatory
      network. Identification of these proteins, combined with their changes in
      abundance, provides a global view of the development-dependent protein changes in
      cotton fibers, and offers a framework for further functional research of target
      proteins associated with fiber development.

PMID- 18823141
TI  - Body cooling causes normalization of cardiac protein expression and function in a
      rat heatstroke model.
AB  - Cardiac dysfunction contributes to heatstroke genesis, which can be ameliorated
      by whole body cooling. A comparative analysis using two-dimensional in-gel
      electrophoresis of cardiac protein patterns is performed in rat controls,
      untreated heatstroke rats, and whole body cooling-treated heatstroke rats. After
      the onset of heatstroke, animals display hypotension and altered cardiac protein
      profiles, which can be reversed by whole body cooling. Thus, the proteomic
      mechanisms exerted by body cooling during heatstroke are elucidated by the
      current results.

PMID- 18823140
TI  - Quantitative analysis of brain nuclear phosphoproteins identifies developmentally
      regulated phosphorylation events.
AB  - Protein phosphorylation is a globally adopted and tightly controlled post
      translational modification, and represents one of the most important molecular
      switching mechanisms that govern the entire spectrum of biological processes. In
      the central nervous system, it has been demonstrated that phosphorylation of key
      proteins mediating chromatin remodeling and gene transcription plays an important
      role controlling brain development, synaptogenesis, learning and memory. Many
      studies have focused on large scale identification of phosphopeptides in brain
      tissue. These studies have identified phosphorylation site specific motifs useful
      for predicting protein kinase substrates. In this study, we applied a previously
      developed quantitative approach, stable isotope labeling of amino acids in
      mammals (SILAM), to quantify changes in the phosphorylation of nuclear proteins
      between a postnatal day one (p1) and a p45 rat brain cortex. Using a 15N labeled
      rat brain as an internal standard, we quantified 705 phosphopeptides in the p1
      cortex and 1477 phosphopeptides in the p45 cortex, which translates to 380 and
      585 phosphoproteins in p1 and p45 cortex, respectively. Bioinformatic analysis of
      the differentially modified phosphoproteins revealed that phosphorylation is
      upregulated on multiple components of chromatin remodeling complexes in the p1
      cortex. Taken together, we demonstrated for the first time the usefulness of
      employing stable isotope labeled rat tissue for global quantitative
      phosphorylation analysis.

PMID- 18823142
TI  - Differential proteomic screen to evidence proteins ubiquitinated upon mitotic
      exit in cell-free extract of Xenopus laevis embryos.
AB  - Post-translational modification of proteins via ubiquitination plays a crucial
      role in numerous vital functions of the cell. Polyubiquitination is one of the
      key regulatory processes involved in regulation of mitotic progression. Here we
      describe a differential proteomic screen dedicated to identification of novel
      proteins ubiquitinated upon mitotic exit in cell-free extract of Xenopus laevis
      embryo. Mutated recombinant His6-tagged ubiquitin (Ubi (K48R)) was added to
      mitotic extract from which we purified conjugated proteins, as well as associated
      proteins in nondenaturing conditions by cobalt affinity chromatography. Proteins
      eluted from Ubi (K48R) supplemented and control extracts were compared by LC
      MS/MS analysis after monodimensional SDS-PAGE. A total of 144 proteins
      potentially ubiquitinated or associated with them were identified. Forty-one
      percent of these proteins were shown to be involved in ubiquitination and/or
      proteasomal degradation pathway confirming the specificity of the screen. Twelve
      proteins, among them ubiquitin itself, were shown to carry a "GG" or "LRGG"
      remnant tag indicating their direct ubiquitination. Interestingly, sequence
      analysis of ubiquitinated substrates carrying these tags indicated that in
      Xenopus cell-free embryo extract supplemented with Ubi (K48R) the majority of
      polyubiquitination occurred through lysine-11 specific ubiquitin chain
      polymerization. The potential interest in this atypical form of ubiquitination as
      well as usefulness of our method in analyzing atypical polyubiquitin species is
      discussed.

PMID- 18823144
TI  - Mechanistic and kinetic insights into the thermally induced rearrangement of
      alpha-pinene.
AB  - The thermal rearrangement of alpha-pinene (1) is interesting from mechanistic as
      well as kinetic point of view. Carrier gas pyrolyses with 1 and its acyclic
      isomers ocimene (2) and alloocimene (3) were performed to investigate the thermal
      network of these hydrocarbons. Kinetic analysis of the major reaction steps
      allows for a deeper insight in the reaction mechanism. Thus it was possible to
      explain the racemization of 1, the formation of racemic limonene (4), and the
      absence of the primary pyrolysis product 2 in the reaction mixture resulting from
      thermal rearrangement of 1. Results supported the conclusion that the reactions
      starting with 1 involve biradical transition states.

PMID- 18823145
TI  - Glucose-based surfactants with hydrogenated, fluorinated, or hemifluorinated
      tails: synthesis and comparative physical-chemical characterization.
AB  - (Hemi)fluorinated hydrophobic chains have been found to minimize the denaturating
      propensity of surfactants toward membrane proteins. The work reported herein
      deals with the synthesis of a new series of non-ionic glucose-based surfactants
      endowed with a hybrid hemifluorocarbon chain. The convergent synthesis is based
      on a one-pot reduction/alkylation of hemifluorinated thioacetate and glucosylated
      trishydroxymethyl acrylamidomethane using NaBH4 in methanol. This "mild"
      alkylation was studied in order to improve yields and to pass up the use of an
      excess of commercially unavailable hemifluorinated thiols. The physical-chemical
      properties in aqueous solution of this novel series were studied by surface
      tension measurement and dynamic light scattering (DLS), as well as their behavior
      upon reverse-phase chromatography, and were compared with those of their
      hydrogenated and perfluorinated analogues. The atypical effect of the additional
      ethyl tip to the fluorinated chain was demonstrated by higher critical micellar
      concentration values and abnormal hydrophobicities measured by reverse-phase
      chromatography. Moreover, according to Israelachvili's concept, DLS studies
      showed that surfactants bearing bulkier polar head self-assemble into small and
      well-defined aggregates, suggesting the formation of spherical micelles rather
      than the cylindrical ones usually observed with classical fluorinated
      surfactants.

PMID- 18823146
TI  - Substituent effects on the ring-opening mechanism of lithium
      bromocyclopropylidenoids to allenes.
AB  - The ring-opening reactions of lithium bromocyclopropylidenoids to allenes have
      been investigated computationally at the B3LYP/6-31G(d) level of theory.
      Formally, two pathways can be considered: the reaction may either proceed in a
      concerted fashion or stepwise with the intermediacy of a free cyclopropylidene.
      In both cases, the loss of the bromide ion determines the kinetic of the
      reaction. The stability of the reactive intermediate, i.e., the carbene, is
      dependent on the substituent. Cyclopropylidenes bearing an electron-donating
      group (+M) are extremely unstable and ring-open readily to the allene. In
      contrast, bromocyclopropylidenoids with electron-withdrawing groups are
      particularly stable species. Here, a high energy barrier needs to be overcome in
      order to split off bromide and to generate the corresponding carbene or allene.
      Still, for most of the monosubstituted cyclopropylidenes investigated during this
      study, the activation energy for the cyclopropylidene to allene rearrangement is
      lower than the energy required for parent compound (X = H) except for X = -SiH3
      and -CF3.

PMID- 18823147
TI  - Hierarchical assembly of ultranarrow alkylamine-coated ZnS nanorods: a
      synchrotron surface X-ray diffraction study.
AB  - The packing of anisotropic ultranarrow nanoparticles ( r <or= 0.5 nm) in Langmuir
      films was investigated for two types of nanoparticles: short ZnS wires coated
      with tetradecylamine and ZnS rods coated with octadecylamine. In situ grazing
      incidence small-angle X-ray scattering (GISAXS) revealed the formation, even
      under zero pressure, of ordered superstructures on the water surface consisting
      of alternating nanoparticles. A hierarchical "packing model" is proposed, based
      on GISAXS, transmission electron microscopy, thermogravimetric analysis, and
      grazing incidence X-ray diffraction of pure surfactant Langmuir films.

PMID- 18823148
TI  - Piezoelectric-potential-controlled polarity-reversible Schottky diodes and
      switches of ZnO wires.
AB  - Using a two-end bonded ZnO piezoelectric-fine-wire (PFW) (nanowire, microwire) on
      a flexible polymer substrate, the strain-induced change in I-V transport
      characteristic from symmetric to diode-type has been observed. This phenomenon is
      attributed to the asymmetric change in Schottky-barrier heights at both source
      and drain electrodes as caused by the strain-induced piezoelectric potential-drop
      along the PFW, which have been quantified using the thermionic emission-diffusion
      theory. A new piezotronic switch device with an "on" and "off" ratio of
      approximately 120 has been demonstrated. This work demonstrates a novel approach
      for fabricating diodes and switches that rely on a strain governed piezoelectric
      semiconductor coupling process.

PMID- 18823149
TI  - Determining the internal quantum efficiency of PbSe nanocrystal solar cells with
      the aid of an optical model.
AB  - We determine the internal quantum efficiency (IQE) of the active layer of PbSe
      nanocrystal (NC) back-contact Schottky solar cells by combining external quantum
      efficiency (EQE) and total reflectance measurements with an optical model of the
      device stack. The model is parametrized with the complex index of refraction of
      each layer in the stack as calculated from ellipsometry data. Good agreement
      between the experimental and modeled reflectance spectra permits a quantitative
      estimate of the fraction of incident light absorbed by the NC films at each
      wavelength, thereby yielding well-constrained QE spectra for photons absorbed
      only by the NCs. Using a series of devices fabricated from 5.1+/-0.4 nm diameter
      PbSe NCs, we show that thin NC cells achieve an EQE and an active layer IQE as
      high as 60+/-5% and 80+/-7%, respectively, while the QE of devices with NC layers
      thicker than about 150 nm falls, particularly in the blue, because of
      progressively greater light absorption in the field-free region of the films and
      enhanced recombination overall. Our results demonstrate that interference effects
      must be taken into account in order to calculate accurate optical generation
      profiles and IQE spectra for these thin film solar cells. The mixed
      modeling/experimental approach described here is a rigorous and powerful way to
      determine if multiple exciton generation (MEG) photocurrent is collected by
      devices with EQE<100%. On the basis of the magnitudes and shapes of the IQE
      spectra, we conclude that the 1,2-ethanedithiol treated NC devices studied here
      do not produce appreciable MEG photocurrent.

PMID- 18823150
TI  - Four new species of Plasmodium from New Guinea lizards: integrating morphology
      and molecules.
AB  - New Guinea is one of the most biodiverse regions of the world, particularly in
      terms of the herpetofauna present, yet surprisingly little is known about the
      parasites that infect these organisms. A survey of diverse scinid and agamid
      lizard hosts from this country showed a diversity of malaria parasites infecting
      these hosts. We combined morphological and morphometric observations of the
      parasites (primarily gametocytes) along with DNA sequence data from the
      mitochondrial cytochrome b and cytochrome oxidase I genes and here describe 4 new
      species of Plasmodium, i.e. Plasmodium minuoviride n. sp., Plasmodium koreafense
      n. sp., Plasmodium megalotrypa n. sp., and Plasmodium gemini n. sp. A fifth
      species, Plasmodium lacertiliae Thompson and Hart 1946, is redescribed based on
      new observations of hosts and localities and additional molecular data. This
      combined morphological and molecular approach is advised for all future
      descriptions of new malaria parasite species, particularly in light of situations
      where every life-history stage is not available.

PMID- 18823151
TI  - A new species of camallanidae from Ageneiosus ucayalensis (Pisces: Siluriformes)
      from Para State, Brazil.
AB  - Procamallanus (Spirocamallanus) belenensis n. sp. is described using light and
      scanning electron microcopy, based on specimens taken from Ageneiosus
      ucayalensis, Castelnau, 1855 (Pisces: Siluriforme), a freshwater fish commonly
      called mandube, in Pard State, Brazil; Procamallanus (Spirocamallanus) rarus is
      recorded from the same host. To our knowledge there are no previous reports of
      nematodes from this fish species. Procamallanus (S.) belenensis is characterized
      by the presence of 8-13 cuticular spiral thickenings coating 2/3 of posterior
      region of the buccal capsule of males and females (the anterior third is smooth);
      small sub-equal spicules; 3 and 4-5 pairs of pre- and post-cloacal papillae,
      respectively; the proportion of muscular and glandular esophagus is 1:1.5-2;
      males present 2 spike-like projections at the tail tip, which are absent in
      females by light microscopy. The most closely related species are Procamallanus
      (Spirocamallanus) inopinatus and Procamallanus (Spirocamallanus) pintoi. The new
      species differs from the most closely related species by the presence of 8-10
      cuticular spiral thickenings in the buccal capsule of males and 9-13 in the
      females, 8 pairs of male clocal papillae (3 pre- and 5 post-cloacal,
      respectively), and only males bearing 2 minute, spike-like projections at the
      posterior end.

PMID- 18823152
TI  - Estrogen, testosterone, and sequential movement in men.
AB  - Behavioral and physiological data suggest that the striatal dopaminergic system
      is important in the production and execution of sequential movements. Striatal
      function is also modulated by sex hormones, and previous studies show that
      estradiol is related to sequential movement in women. The authors examined
      whether sex hormones are involved in the production of sequential movement in
      healthy older and younger men. Testosterone was modified for a 6-week period such
      that levels in older men matched those of younger men, the conversion of
      testosterone to estradiol was blocked, the production of testosterone was
      blocked, or the men received no treatment (placebo). Sequential movement was
      measured before and after hormone treatment. Older men were slower and more
      accurate than younger men on the sequential movement task pre- and posttreatment.
      Hormone manipulation had no effect on movement speed. Hormone levels were not
      correlated with sequential movement performance in either older or younger men,
      suggesting that sex hormones do not modulate sequential movement in men, and
      hormone replacement may not restore a loss of sequential movement ability in
      elderly men or men with Parkinson's disease.

PMID- 18823153
TI  - The paternally expressed gene Peg3 regulates sexual experience-dependent
      preferences for estrous odors.
AB  - Sexual experience has marked and long-lasting effects on male behavior in
      mammals, regulating traits such as the anticipation and display of sexual
      behavior, aggression, and olfaction. The authors conducted urine preference,
      habituation-dishabituation, and partner choice tests with sexually experienced
      and naive male mice and found that wild-type males acquire adaptively significant
      preferences for the odors of receptive, estrous females with sexual experience,
      and that these preferences are matched by changes in main olfactory system
      responses involving the piriform cortex, as indicated by c-Fos expression. The
      authors also report that these experiential effects are disrupted in male mice
      carrying a knockout of the imprinted gene Peg3. This paternally expressed gene
      regulates maternal care and offspring development, but the authors here report
      that Peg3 mutant males suffer a complex olfactory deficit that affects estrous
      odor preferences and the responses of the main olfactory system to such odors.
      Peg3 appears to have evolved to regulate the experience-dependent preference for
      receptive females, an adaptive trait that would enhance male reproductive success
      and so potentially increase paternal transmission of this paternally expressed
      gene.

PMID- 18823155
TI  - Male and female mice differ for baseline and nicotine-induced event related
      potentials.
AB  - The usage patterns and biological effects of cigarette smoking differ
      significantly among men and women. This study seeks to clarify the interaction
      that exists between nicotine and biological gender by investigating changes in
      brain electrical activity after acute nicotine treatment. The P20, N40, and P80
      components of the auditory evoked potential were examined in male and female
      C57BL/6J mice using a paired-stimulus gating paradigm. Consistent with previously
      published data, acute nicotine resulted in increased gating of the P20 but a
      decrease in that of N40. Nicotine also resulted in a lengthening of P20 latency
      but a decrease in that of N40 and P80. The P80 latencies of male and female
      subjects were differentially affected by nicotine, as males appeared to be more
      sensitive to its shortening effect. Males and females also exhibited differences
      in N40 and P80 amplitudes, both of which were smaller in males. The effects of
      gender on auditory evoked potential amplitude suggest dimorphic signaling in the
      N40 and P80 generators. Whether this electrophysiological sexual dimorphism has
      functional consequences for sensory or cognitive abilities requires additional
      research. (PsycINFO Database Record (c) 2008 APA, all rights reserved).

PMID- 18823154
TI  - Estradiol or diarylpropionitrile decrease anxiety-like behavior of wildtype, but
      not estrogen receptor beta knockout, mice.
AB  - Clinical and basic studies demonstrate that estrogen (E-sub-2)-based therapies
      influence anxiety and mood, but the receptor targets (e.g., a or ss isoform of
      the estrogen receptor, ER) for these effects requires further investigation. To
      address the specificity of E2's anxiolytic-like effects through ERss, anxiety,
      motor, and nociceptive behavior of ovariectomized, wildtype (WT), and ERss
      knockout (ssERKO) mice was examined. Mice were administered oil vehicle or ER
      agonists, 17ss-E2 (E2; 0.1 mg/kg; similar affinity for ERa and ERss), and a
      selective ER modulator, diarylpropionitrile (DPN; 0.1 mg/kg; greater affinity for
      ERss than ERa). Performance of mice in anxiety (open field, elevated plus maze,
      elevated zero maze, social interaction), motor activity (activity monitor) and
      nociception (tailflick, pawlick) measures was compared. Results supported our
      hypothesis that ERss is important in modulation of anxiety-like behavior by E2 in
      some tasks. Administration of E2 or DPN to WT, but not ssERKO, mice increased
      open field central entries, plus maze open arm time, zero maze open quadrant
      time, and social interaction. This pattern was neither seen in motor activity nor
      pain threshold measures. Thus, actions of ERss may be important for modulating
      anxiety-like behavior of mice.

PMID- 18823156
TI  - Context-dependent acquisition of copulatory behavior in the male rat: role of
      female availability.
AB  - The effect of the environment in which sexual experience is acquired was examined
      on patterns of male rat copulatory behavior. Males trained in a pacing chamber
      with a 4-hole partition had significantly shorter ejaculation latencies compared
      with males trained in chambers with a 1-hole partition. Those differences
      persisted when males were switched into the other pacing condition, suggesting
      that the pattern of copulation in these males had become "fixed." In the second
      experiment, males were trained to associate an almond odor with copulation in
      either the 1-hole or 4-hole condition. Males ejaculated preferentially with
      females associated with the 4-hole pacing condition. Copulatory behavior in male
      rats is sensitive to female availability, and females associated with greater
      availability are preferred.

PMID- 18823157
TI  - The reproductive stage and experience of sexually receptive mothers alter their
      preference for pups or males.
AB  - Female rats show postpartum estrus, a unique stage in their reproductive cycle in
      which they are able to display maternal and sexual responses at the same time. To
      assess the relative value of pups or males for sexually receptive mothers with
      different hormonal profiles and reproductive experiences, we employed a 3-point
      star maze with 3 choice compartments containing: pups, a sexually active male, or
      no stimulus (neutral). Cycling maternal and nonmaternal females in late
      proestrus, independently of their previous reproductive experience, strongly
      preferred the male to the pups, although most postpartum estrous dams did not
      exhibit preference for the male. The majority of the postpartum primiparous
      females did not prefer the litter's chamber either, but a previous reproductive
      experience strongly determined their preference for the pups. These results
      suggest that the hormonal changes of the proestrus, in contrast to those of the
      postpartum estrus, promote a strong preference for the male that is not
      diminished by the maternal condition. Conversely, the endocrine changes of the
      postpartum facilitate the effect of previous reproductive experience in
      strengthening the incentive value of the pups.

PMID- 18823158
TI  - Emergence of stereotypies in juvenile monkeys (Macaca mulatta) with neonatal
      amygdala or hippocampus lesions.
AB  - The emergence of stereotypies was examined in juvenile rhesus monkeys (Macaca
      mulatta) who, at 2 weeks of postnatal age, received selective bilateral ibotenic
      acid lesions of the amygdala (N = 8) or hippocampus (N = 8). The lesion groups
      were compared to age-matched control subjects that received a sham surgical
      procedure (N = 8). All subjects were maternally reared for the first 6 months and
      provided access to social groups throughout development. Pronounced stereotypies
      were not observed in any of the experimental groups during the first year of
      life. However, between 1 to 2 years of age, both amygdala- and hippocampus
      lesioned subjects began to exhibit stereotypies. When observed as juveniles, both
      amygdala- and hippocampus-lesioned subjects consistently produced more
      stereotypies than the control subjects in a variety of contexts. More
      interesting, neonatal lesions of either the amygdala or hippocampus resulted in
      unique repertoires of repetitive behaviors. Amygdala-lesioned subjects exhibited
      more self-directed stereotypies and the hippocampus-lesioned subjects displayed
      more head-twisting. We discuss these results in relation to the neurobiological
      basis of repetitive stereotypies in neurodevelopmental disorders, such as autism.

PMID- 18823159
TI  - Timing of extinction relative to acquisition: a parametric analysis of fear
      extinction in humans.
AB  - Fear extinction is a reduction in conditioned fear following repeated exposure to
      the feared cue in the absence of any aversive event. Extinguished fear often
      reappears after extinction through spontaneous recovery. Animal studies suggest
      that spontaneous recovery can be abolished if extinction occurs within minutes of
      acquisition. However, a limited number of human extinction studies have shown
      that short interval extinction does not prevent the return of fear. For this
      reason, we performed an in-depth parametric analysis of human fear extinction
      using fear-potentiated startle. Using separate single-cue and differential
      conditioning paradigms, participants were fear conditioned and then underwent
      extinction either 10 min (Immediate) or 72 hr (Delayed) later. Testing for
      spontaneous recovery occurred 96 hr after acquisition. In the single cue
      paradigm, the Immediate and Delayed groups exhibited differences in context, but
      not fear, conditioning. With differential conditioning, there were no differences
      in context conditioning and the Immediate group displayed less spontaneous
      recovery. Thus, the results remain inconclusive regarding spontaneous recovery
      and the timing of extinction and are discussed in terms of performing
      translational studies of fear in humans.

PMID- 18823160
TI  - Working memory across nostrils.
AB  - Whether olfactory working memory involves verbal representations or neural images
      of odor per se remains unclear. This study investigated whether verbal
      representation influences performance in an olfactory delayed-match-to-sample
      task and used monorhinal presentation to generate hypotheses as to the underlying
      anatomy of this mechanism. The main findings were that (a) nameable odorants were
      easier to remember than hard-to-name odorants and (b) the nameability effect was
      more pronounced when the evaluation was done across nostrils. Considering these
      results within a proposed model implies dual representation in olfactory working
      memory: All odors, nameable and hard to name, are represented both perceptually
      and verbally.

PMID- 18823162
TI  - Reduced palatability in lithium- and activity-based, but not in amphetamine
      based, taste aversion learning.
AB  - Conditioned taste aversions (CTA) based on lithium chloride (Experiment 1),
      amphetamine (Experiment 2), and wheel running (Experiment 3) were examined using
      the analysis of the microstructure of licking to measure the palatability of the
      taste serving as the conditioned stimulus (CS). Pairing saccharin with
      amphetamine reduced saccharin intake without reducing the size of licking
      clusters, initial lick rate, or the distribution of inter-lick intervals (ILIs)
      within a cluster. By contrast, pairing saccharin with lithium or wheel-running
      reduced saccharin intake as well as lick cluster size, initial lick rate, and the
      distribution of ILIs within a cluster. As lick cluster size, initial lick rate,
      and ILI distribution can be used as indices of stimulus palatability, the current
      results indicate that taste aversions based on either lithium or activity reduced
      the palatability of the CS. This suggests that aversions based on both lithium
      and wheel running involve conditioned nausea to the CS taste. The absence of
      similar changes in licking microstructure with amphetamine-based CTA is
      consistent with other evidence indicating this does not involve nausea.

PMID- 18823161
TI  - Gustatory insular cortex lesions disrupt drug-induced, but not lithium chloride
      induced, suppression of conditioned stimulus intake.
AB  - Rats suppress intake of a normally preferred 0.15% saccharin conditioned stimulus
      (CS) when it is paired with an aversive agent like lithium chloride (LiCl) or a
      preferred substance such as sucrose or a drug of abuse. The reward comparison
      hypothesis suggests that rats avoid intake of a saccharin cue following pairings
      with a drug of abuse because the rats are anticipating the availability of the
      rewarding properties of the drug. The present study used bilateral ibotenic acid
      lesions to examine the role of the gustatory cortex in the suppression of CS
      intake induced by cocaine, morphine, and LiCl. The results show that bilateral
      lesions of the insular gustatory cortex (1) fully prevent the suppressive effects
      of both a 15 and a 30 mg/kg dose of morphine, (2) attenuate the suppressive
      effect of a 10 mg/kg dose of cocaine, but (3) are overridden by a 20 mg/kg dose
      of the drug. Finally, these same cortical lesions had no impact on LiCl-induced
      conditioned taste aversion. The current data show that the insular taste cortex
      plays an integral role in drug-induced avoidance of a gustatory CS.

PMID- 18823163
TI  - Central CRF receptor antagonist a-helical CRF9-41 blocks reinstatement of
      extinguished fear: the role of the bed nucleus of the stria terminalis.
AB  - The present experiments assessed the necessity of central CRF in reinstatement of
      extinguished fear. Using the fear-potentiated startle procedure, rats were given
      light-shock pairings (fear conditioning) followed by light-alone extinction
      training. Rats were then given unsignaled shocks to reinstate fear to the light
      conditioned stimulus (CS). Intracerebroventricular administration of the CRF
      antagonist a-Helical CRF9-41 prior to reinstatement training dose-dependently
      prevented reinstatement. Further, a-Helical CRF9-41 administration prior to
      reinstatement training or the test for reinstatement of fear to the extinguished
      CS prevented reinstatement at both treatment times, suggesting that CRF activity
      is critical for this type of return of fear to an extinguished CS. The abolition
      of reinstatement by drug administration was not due to state-dependent learning,
      as rats treated with the drug prior to both reinstatement training or testing
      also failed a-Helical CRF9-41 in the bed nucleus of the stria terminalis
      suggested that this area is a site at which central CRF is involved in this form
      of relapse.

PMID- 18823164
TI  - Neurotoxic lesions of retrosplenial cortex disrupt signaled and unsignaled
      contextual fear conditioning.
AB  - The majority of research regarding contextual learning and memory has focused on
      the contributions of the hippocampus and related medial temporal lobe structures.
      However, little is known about other possible cortical contributions to these
      processes. Our laboratory recently demonstrated that electrolytic lesions of the
      retrosplenial cortex (RSP), a posterior region of cingulate cortex, impaired
      contextual but not cue-specific fear conditioning. The present experiments
      further examined the role of RSP in contextual fear memory using fiber-sparing
      neurotoxic lesions and both signaled and unsignaled fear conditioning paradigms.
      Despite comparable acquisition of the conditioned fear response, rats with
      neurotoxic lesions of RSP exhibited impaired contextual memory relative to
      control animals in both the signaled and unsignaled paradigms. These results
      further suggest an important role for RSP in contextual learning and memory.

PMID- 18823165
TI  - A morphine-paired environment alters c-Fos expression in the forebrain of rats
      displaying conditioned place preference or aversion.
AB  - The question of whether a common mechanism mediates both aversive and rewarding
      drug-paired cues is still unclear. In this study, we used a place preference
      conditioning paradigm to train rats to associate 1 chamber with morphine and the
      other chamber with saline. On the test day, rats were divided into those
      displaying conditioned place preferences (CPP) versus conditioned place aversion
      (CPA). After the test, all rats were killed and c-Fos immunocytochemistry was
      performed. For the control group, rats were treated with the same procedure
      except that the injections of morphine or saline had no association with the
      chambers. Compared with the control group, the CPP and CPA groups showed a
      significant increase of c-Fos expression in the dorsomedial striatum, central
      medial nucleus of the thalamus, and the basolateral amygdala. However, we saw no
      difference between CPP and CPA rats in any brain region examined. These results
      suggest that a morphine-paired environment can elicit neural activity in brain
      regions that are involved in emotional learning. Morphine-conditioned place
      preference and aversion may share a common neural circuitry elicited by a
      morphine-paired environment.

PMID- 18823166
TI  - Hippocampal response patterns during discriminative eyeblink/jaw movement
      conditioning in the rabbit.
AB  - Rabbits were given concurrent training in eyeblink (EB) and jaw movement (JM)
      conditioning in which 1 tone predicted an airpuff and another tone predicted
      water. After 10 days of discrimination training, the animals were given 10 days
      of reversal training. In the discrimination phase, acquisition of the 2
      conditioned responses was not significantly different; however JM discrimination
      errors were much more frequent than were EB errors. In the reversal phase,
      correct performance on EB trials increased gradually, as was expected, whereas
      there was immediate behavioral reversal on JM trials. Differences in size and
      topography of dorsal CA1 multiple-unit responses reflected the ability of the
      hippocampus to discriminate between stimuli in trained animals, corresponding to
      the performance of the behavioral discrimination. During JM trials, the
      rhythmicity of the neural response was further modulated by the type of the prior
      trial, suggesting the coding of sequential events by the hippocampus. Thus,
      hippocampal conditioned activity can rapidly change its magnitude and pattern
      depending on the specific trial type during a concurrent EB/JM discrimination
      task and its reversal. (PsycINFO Database Record (c) 2008 APA, all rights
      reserved).

PMID- 18823167
TI  - Neural dynamics underlying impaired autonomic and conditioned responses following
      amygdala and orbitofrontal lesions.
AB  - A neural model is presented that explains how outcome-specific learning modulates
      affect, decision-making, and Pavlovian conditioned approach responses. The model
      addresses how brain regions responsible for affective learning and habit learning
      interact and answers a central question: What are the relative contributions of
      the amygdala and orbitofrontal cortex to emotion and behavior? In the model, the
      amygdala calculates outcome value while the orbitofrontal cortex influences
      attention and conditioned responding by assigning value information to stimuli.
      Model simulations replicate autonomic, electrophysiological, and behavioral data
      associated with three tasks commonly used to assay these phenomena: Food
      consumption, Pavlovian conditioning, and visual discrimination. Interactions of
      the basal ganglia and amygdala with sensory and orbitofrontal cortices enable the
      model to replicate the complex pattern of spared and impaired behavioral and
      emotional capacities seen following lesions of the amygdala and orbitofrontal
      cortex.

PMID- 18823168
TI  - The reinforcement mountain: allocation of behavior as a function of the rate and
      intensity of rewarding brain stimulation.
AB  - The single-operant matching law has been used to describe the relationship
      between time allocated to pursuit of brain stimulation reward (BSR) and the
      obtained rate of reinforcement. We generalize this relationship to a third
      dimension by including the strength of the stimulation (the number of pulses per
      train) as an independent dimension, and we dub the resulting 3-dimensional
      structure "the reinforcement mountain." The validity of generalizing the single
      operant matching law in this way was assessed by determining the changes in the
      position of the mountain produced by increasing the stimulation current or the
      train duration. Most of the predictions were supported, and the mountain model
      fitted the data closely. It is argued that application of this model can remove
      ambiguity inherent in 2-dimensional descriptions of operant performance and can
      reveal whether lesions, drugs, or physiological manipulations that alter
      performance for BSR act before or after the output of the ("reward-growth")
      function that translates the electrically induced impulse flow into the intensity
      of the BSR.

PMID- 18823169
TI  - Responses of pigeon (Columba livia) Wulst neurons during acquisition and reversal
      of a visual discrimination task.
AB  - The avian visual "Wulst" is a target of the ascending thalamofugal visual
      pathway. In pigeons (Columba livia), lesion damage to the Wulst has little effect
      on simple visual discriminations, but impairs performance on tasks such as
      reversal learning. We recorded the responses of single Wulst neurons as pigeons
      were trained on the acquisition and subsequent reversal of a visual
      discrimination. Of the 64 units recorded, 54 (84%) displayed a significant
      difference in firing rate between some component of the task and the intertrial
      interval that separated trials. More important, 14 units (22%) displayed a
      significant change in firing rate exclusively to the S+ and/or S- as learning
      progressed either during acquisition or reversal. The responses of these 14
      neurons indicate that learning during initial acquisition was as likely to
      correlate with a change in firing rate as during reversal, and some neuronal
      responses could be characterized as representing reward properties together with
      visual stimulus features. As such, responses of pigeon Wulst neurons indicate a
      role in representing aspects of learning as much as the physical/perceptual
      properties of visual stimuli.

PMID- 18823170
TI  - Noradrenergic neurotoxin, N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine
      hydrochloride (DSP-4), treatment eliminates estrogenic effects on song
      responsiveness in female zebra finches (Taeniopygia guttata).
AB  - Female songbirds use male songs as an important criterion for mate selection.
      Several studies have reported that female songbirds prefer complex songs to other
      song types. In a recent study, the authors found that song responsiveness in
      female zebra finches (Taeniopygia guttata) is strongly modulated by circulating
      estrogen levels. The behavioral effects of estrogen are often mediated via
      norepinephrine (NE). The current study administered the noradrenergic neurotoxin,
      N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride (DSP-4) to estradiol
      treated female zebra finches to investigate if estrogenic effects on song
      responsiveness are mediated via NE. The authors tested song responsiveness of
      adult female zebra finches for three acoustically different song types--simple,
      long-bout, and complex--under three treatment conditions, untreated, estradiol
      treated, and estradiol + DSP-4-treated. Females only showed differential song
      responsiveness when treated with estradiol alone, responding more to complex
      songs. DSP-4 treatment eliminated this differential responsiveness. The results
      are discussed in the light of evidence from functional, neurochemical, and
      neuroanatomical studies that suggest that estrogenic effects on song processing
      might be mediated by NE.

PMID- 18823171
TI  - Nicotine enhances context learning but not context-shock associative learning.
AB  - Nicotine has been found to enhance learning in a variety of tasks, including
      contextual fear conditioning. During contextual fear conditioning animals have to
      learn the context and associate the context with an unconditioned stimulus
      (footshock). As both of these types of learning co-occur during fear
      conditioning, it is not clear whether nicotine enhances one or both of these
      types of learning. To tease these two forms of learning apart, the authors made
      use of the context preexposure facilitation effect (CPFE). Acquisition of the
      CPFE requires that contextual and context-shock learning occurs on separate days,
      allowing for their individual manipulation. Nicotine (0.09 mg/kg) administered
      prior to contextual learning and retrieval enhanced the CPFE whereas
      administration prior to context-shock learning and retrieval had no effect. Thus,
      nicotine enhances contextual learning but not context-shock associative learning.
      Finally, the results are discussed in terms of a theory of how nicotine could
      alter hippocampal-cortical-amygdala interactions to facilitate contextual
      learning.

PMID- 18823172
TI  - Varenicline ameliorates nicotine withdrawal-induced learning deficits in C57BL/6
      mice.
AB  - Varenicline, a partial agonist for a4ss2 nicotinic acetylcholine receptors
      (nAChRs) and full agonist for a7 nAChRs, has been approved for the treatment of
      smoking cessation. Although recent clinical trials support the efficacy of
      varenicline for managing global nicotine withdrawal symptoms and for smoking
      cessation, its effects on animal models of specific withdrawal-associated
      behaviors have not been tested. The present study evaluated the effects of
      varenicline on contextual fear conditioning and its effects on nicotine (6.3
      mg/kg/day) withdrawal-induced deficits in contextual fear conditioning.
      Varenicline (0.01, 0.1, 1.0 mg/kg) had no effect on contextual fear conditioning
      when administered alone, but (0.1 mg/kg) prevented nicotine withdrawal-associated
      deficits in contextual fear conditioning. These data demonstrate, for the first
      time, that varenicline reverses nicotine withdrawal-induced deficits in an animal
      model and suggest that varenicline may be effective at treating nicotine
      withdrawal-associated deficits in learning and memory.

PMID- 18823173
TI  - Insulin receptor substrate-2 in the ventral tegmental area regulates behavioral
      responses to cocaine.
AB  - Neurotrophic factor signaling modulates cellular and behavioral responses to
      drugs of abuse. Among other biochemical adaptations, chronic exposure to abused
      drugs decreases the expression of insulin receptor substrate-2 (IRS-2; a protein
      involved in neurotrophic signaling) in the ventral tegmental area (VTA), a neural
      substrate for many drugs of abuse. Using viral-mediated gene transfer to locally
      alter the activity of IRS-2, the authors show that overexpression of IRS-2 in the
      VTA results in an enhanced preference for environments previously paired with
      cocaine, as measured by the place conditioning paradigm, whereas blockade of IRS
      2 activity results in avoidance of cocaine-paired compartments. In addition, IRS
      2 overexpression leads to enhanced cocaine-induced locomotor activity, and
      blockade of IRS-2 expression significantly blunts behavioral responses to
      cocaine. These results demonstrate that levels of IRS-2 in the VTA regulate
      responsiveness to the behavioral effects of cocaine.

PMID- 18823174
TI  - Fear conditioning to discontinuous auditory cues requires perirhinal cortical
      function.
AB  - Pretraining lesions of rat perirhinal (PR) cortex impair fear conditioning to
      ultrasonic vocalizations (USVs) but have no effect on conditioning to continuous
      tones. This study attempted to deconstruct USVs into simpler stimulus features
      that cause fear conditioning to be PR-dependent. Rats were conditioned to one of
      three cues: a multicall 19-kHz USV, a 19-kHz discontinuous tone, and a 19-kHz
      continuous tone. The discontinuous tone duplicated the on/off pattern of the
      individual calls in the USV, but it lacked the characteristic frequency
      modulations. Well-localized neurotoxic PR lesions impaired conditioning to the
      USV, the discontinuous tone, and the training context. However, PR lesions had no
      effect on conditioning to the continuous tone. The authors suggest that the
      lesion effects on fear conditioning to both cues and contexts reflect the
      essential role of PR in binding stimulus elements together into unitary
      representations.

PMID- 18823175
TI  - What does it take to demonstrate memory erasure? Theoretical comment on Norrholm
      et al. (2008).
AB  - An issue of increasing interest in Pavlovian conditioning is to identify ways to
      facilitate the development and persistence of extinction. Both behavioral and
      molecular lines of evidence demonstrate that learning during extinction can be
      enhanced. Similar evidence has been offered to support the idea that extinction
      causes the original association to be unlearned, or erased. Differentiating
      between extinction and erasure accounts is extremely difficult and requires many
      assumptions about the fundamental nature of how memory storage maps into memory
      expression. In this issue of Behavioral Neuroscience, Norrholm et al. (see record
      2008-13280-002) describe a study of extinction with humans that has the potential
      to serve as a translational bridge between rodent work and clinical applications.
      They find less recovery of a conditioned fear response when extinction occurs 10
      min compared with 72 hr after conditioning; however, the recovery of subjects'
      expectancies of the fearful stimulus is independent of when extinction occurred.
      These findings and others discussed in this article demonstrate some of the
      challenges in making inferences about memory erasure during extinction.

PMID- 18823176
TI  - Do conscientious individuals live longer? A quantitative review.
AB  - OBJECTIVE: Following up on growing evidence that higher levels of
      conscientiousness are associated with greater health protection, the authors
      conducted a meta-analysis of the association between conscientiousness-related
      traits and longevity. DESIGN: Using a random-effects analysis model, the authors
      statistically combined 20 independent samples. In addition, the authors used
      fixed-effects analyses to examine specific facets of conscientiousness and study
      characteristics as potential moderators of this relationship. MAIN OUTCOME
      MEASURES: Effect sizes were computed for each individual sample as the
      correlation coefficient r, based on the relationship between conscientiousness
      and mortality risk (all-cause mortality risk, longevity, or length of survival).
      RESULTS: Higher levels of conscientiousness were significantly and positively
      related to longevity (r = .11, 95% confidence interval = .05-.17). Associations
      were strongest for the achievement (persistent, industrious) and order
      (organized, disciplined) facets of conscientiousness. CONCLUSION: Results
      strongly support the importance of conscientiousness-related traits to health
      across the life span. Future research and interventions should consider how
      individual differences in conscientiousness may cause and be shaped by health
      relevant biopsychosocial events across many years.

PMID- 18823177
TI  - Physician and patient communication training in primary care: effects on
      participation and satisfaction.
AB  - OBJECTIVE: To assess the effects of a communication skills training program for
      physicians and patients. DESIGN: A randomized experiment to improve physician
      communication skills was assessed 1 and 6 months after a training intervention;
      patient training to be active participants was assessed after 1 month. Across
      three primary medical care settings, 156 physicians treating 2,196 patients were
      randomly assigned to control group or one of three conditions (physician,
      patient, or both trained). MAIN OUTCOME MEASURES: Patient satisfaction and
      perceptions of choice, decision-making, information, and lifestyle counseling;
      physicians' satisfaction and stress; and global ratings of the communication
      process. RESULTS: The following significant (p < .05) effects emerged: physician
      training improved patients' satisfaction with information and overall care;
      increased willingness to recommend the physician; increased physicians'
      counseling (as reported by patients) about weight loss, exercise, and quitting
      smoking and alcohol; increased physician satisfaction with physical exam detail;
      increased independent ratings of physicians' sensitive, connected communication
      with their patients, and decreased physician satisfaction with interpersonal
      aspects of professional life. Patient training improved physicians' satisfaction
      with data collection; if only physician or patient was trained, physician stress
      increased and physician satisfaction decreased. CONCLUSION: Implications for
      improving physician-patient relationship outcomes through communication skills
      training are discussed.

PMID- 18823178
TI  - The psychobiology of trait shame in young women: extending the social self
      preservation theory.
AB  - OBJECTIVE: The social self preservation theory (SSPT) proposes that social
      evaluative threat evokes the emotion of shame, which then shapes a coordinated
      psychobiological response. While this is supported in acute stress studies, there
      is no data on chronic experiences of shame. DESIGN: We investigated the
      association of trait shame with activity of the hypothalamic-pituitary-adrenal
      (HPA) axis, of the sympathetic nervous system (SNS), and regulation of
      inflammation in n = 56 young women. MAIN OUTCOME MEASURES: Daily profiles of
      salivary cortisol and alpha-amylase were assessed as indices of HPA axis and SNS
      activity, respectively. Inflammatory regulation was assessed by
      lipopolysaccharide-stimulated production and glucocorticoid inhibition of
      interleukin-6 in vitro. RESULTS: Trait shame was associated with SNS (r = .49; p
      = .001), but not HPA activity (r = .14; ns). Shame was associated with
      inflammatory activity (r = .35; p = .006) and glucocorticoid sensitivity (r = 
      0.43; p = .001). Relationships were not mediated by HPA and SNS activity.
      CONCLUSIONS: Results support SSPT predictions with respect to chronic shame
      experience and inflammation. Results further suggest the importance of SNS
      activation related to shame, and the possibility that HPA activation may be
      limited acute experiences of shame.

PMID- 18823179
TI  - Are we aware of the external factors that influence our food intake?
AB  - OBJECTIVES: This research examines the extent to which people accurately report
      some of the external influences on their food intake. DESIGN: In two studies,
      specific factors (the presence and behavior of others) were manipulated in order
      to influence the amount of food that individuals consumed. MAIN OUTCOME MEASURES:
      The main outcomes of interest were participants' spontaneously generated
      explanations for their food intake (Study 1; n = 122), and their ratings of the
      importance of several potential determinants of food intake (Study 2; n = 75).
      RESULTS: In Study 1, there was high concordance between the amounts eaten by
      members of a dyad, but very few participants indicated that they were influenced
      by their partner's behavior; they instead identified hunger and taste as the
      primary determinants of intake. Study 2 showed that participants' intake was
      strongly influenced by the behavior of others, but people rated taste and hunger
      as much more important influences on their intake. CONCLUSIONS: If external
      environmental factors influence people's food intake without their awareness or
      acknowledgment, then maintaining a healthy diet can be a challenge, with long
      term consequences for health and well-being.

PMID- 18823180
TI  - Timing of dietary change in response to a telephone counseling intervention:
      evidence from the WHEL study.
AB  - OBJECTIVE: Little is known about temporal patterns of diet change within
      interventions, nor about predictors of early and sustained successful change.
      Social-cognitive theory asserts that early successes in achieving behavior change
      increase self-efficacy, leading to longer-term success. DESIGN: The authors
      conducted exploratory cluster analyses using dietary data from the first month of
      the telephone counseling intervention of the Women's Healthy Eating and Living
      (WHEL) Study. MAIN OUTCOME MEASURE: Change in dietary pattern at three early
      intervention timepoints. RESULTS: Three clusters were identified: Cluster 1 (25%)
      was close to meeting study goals at baseline, but still made major changes;
      Cluster 2 (49%) and Cluster 3 (26%) were not achieving study goals at baseline,
      but Cluster 2 made substantial immediate changes, while Cluster 3 changed their
      diet more gradually. Baseline demographic and behavioral variables were
      associated with cluster membership; however, the strongest predictors of cluster
      were self-efficacy, motivation, and approaches to study goals. Cluster membership
      predicted dietary pattern at 12 months. CONCLUSION: These data suggest that a one
      on-one telephone counseling intervention that is intensive in the early weeks may
      maximize the level of change achieved in a study.

PMID- 18823181
TI  - Analyzing the transtheoretical model using the framework of Weinstein, Rothman,
      and Sutton (1998): the example of smoking cessation.
AB  - OBJECTIVE: To assess the transtheoretical model applied to smoking cessation
      using the framework of N. D. Weinstein, A. J. Rothman, and S. R. Sutton (1998),
      which is the general framework for designing and evaluating stage models of
      health behavior. DESIGN: Systematic review. RESULTS AND CONCLUSION: The
      transtheoretical model applied to smoking cessation does not satisfy the criteria
      required of a valid stage model. Most significantly, the evidence indicates that
      the stages of change are not qualitatively distinct categories.

PMID- 18823182
TI  - A volitional help sheet to encourage smoking cessation: a randomized exploratory
      trial.
AB  - OBJECTIVE: The volitional help sheet draws on Gollwitzer's (1993) concept of
      implementation intentions by encouraging smokers to link temptations to smoke
      with appropriate behavioral responses derived from Prochaska and DiClemente's
      (1983) transtheoretical model. DESIGN: There were 193 smokers who were randomly
      allocated to receive questionnaires, planning instruction, and a volitional help
      sheet or one of three control conditions: Questionnaire-only; questionnaire plus
      planning instruction; or questionnaire, planning instruction plus volitional help
      sheet without the explicit instruction to link temptations to smoke with
      appropriate behavioral responses. MAIN OUTCOME MEASURES: Nicotine dependence,
      number of cigarettes smoked and quit status. RESULTS: Findings revealed
      significant decreases in nicotine dependence, number of cigarettes smoked, and
      increases in quitting in the volitional help sheet condition, relative to the
      control conditions, Fs(3, 189) = 7.48 to 10.78, ps < .01, eta 2 p s = .11 to .15.
      This pattern of findings did not hold for social?cognitive variables, with few
      differences between the volitional help sheet (standard instructions) group and
      the other conditions. CONCLUSION: The findings provide support for the use of
      implementation intentions to protect against health risk behaviors and are
      congruent with laboratory research showing that implementation intentions are a
      case of strategic automaticity.

PMID- 18823183
TI  - The effects of physical fitness and feeling vigorous on self-rated health.
AB  - OBJECTIVE: We prospectively studied the hypothesized beneficial effects of
      feeling vigorous and of objective physical fitness (gauged based on functional
      capacity) on subsequently assessed self-rated health (SRH), controlling for
      possible confounders known to be precursors of SRH and of our predictors. We also
      investigated the reverse-causation hypothesis that SRH predicts subsequent vigor
      and functional capacity. DESIGN: Participants were apparently healthy employees
      (N = 779) who underwent a routine health check at two points of time, Time 1 (T1)
      and Time 2 (T2), about 18 months apart. We used regression analysis, predicting
      T2 SRH by T1 SRH, the control variables, and T1vigor and functional capacity.
      MAIN OUTCOME MEASURES: Vigor was assessed using the Shirom-Melamed Vigor Measure;
      objective physical fitness was indicated by functional capacity following a
      treadmill exercise, and self-rated health was measured by a single item. RESULTS:
      As hypothesized, we found that the change in T2 SRH was positively predicted by
      T1 vigor, functional capacity, and their interactive term. Testing the reverse
      causation paths, we found that T1 SRH did not predict subsequent functional
      capacity and was a relatively weak predictor of subsequent vigor. CONCLUSION: The
      affective state of vigor and objectively assessed functional capacity interact to
      predict subsequent changes in self-rated health.

PMID- 18823184
TI  - Association between socioeconomic status and metabolic syndrome in women: testing
      the reserve capacity model.
AB  - OBJECTIVE: Low socioeconomic status (SES) environments may impede the development
      of a bank of resources, labeled reserve capacity, and may also be stressful,
      thereby depleting available reserves. In consequence, lower SES persons may
      experience more negative emotions, leading to adverse health consequences. The
      authors tested the reserve capacity model in relation to the metabolic syndrome.
      DESIGN: There were 401 initially healthy women who followed longitudinally for 12
      years. Self-reported characteristics, stressors, and cardiovascular risk factors
      were measured repeatedly. Structural equation modeling was used to evaluate
      hypothesized relationships. MAIN OUTCOME MEASURE: Metabolic syndrome factor.
      RESULTS: Confirmatory factor analysis verified reserve capacity as the aggregate
      of optimism, self-esteem, and social support, and negative emotion as the
      aggregate of depressive symptoms, anger, and tension. Structural equation
      modeling showed two pathways to the metabolic syndrome factor, (chi2(59) =
      111.729, p < .0001 chi2/df = 1.894; CFI = .956; RMSEA = .047): direct from low
      SES to the metabolic syndrome factor (B = -0.19, t = -3.24, p = .001); and
      indirect, from low SES to low reserve capacity to high negative emotions to the
      metabolic syndrome factor (B = -0.024, t = -2.05, p = .04). CONCLUSION: Low SES
      may increase risk for metabolic syndrome, in part, through reserve capacity and
      negative emotions.

PMID- 18823185
TI  - Long-term effects of lifestyle changes on well-being and cardiac variables among
      coronary heart disease patients.
AB  - OBJECTIVE: To focus on psychological well-being in the Lifestyle Heart Trial
      (LHT), an intensive lifestyle intervention including diet, exercise, stress
      management, and group support that previously demonstrated maintenance of
      comprehensive lifestyle changes and reversal of coronary artery stenosis at 1 and
      5 years. DESIGN AND MAIN OUTCOME MEASURES: The LHT was a randomized controlled
      trial using an invitational design. The authors compared psychological distress,
      anger, hostility, and perceived social support by group (intervention group, n =
      28; control group, n = 20) and time (baseline, 1 year, 5 years) and examined the
      relationships of lifestyle changes to cardiac variables. RESULTS: Reductions in
      psychological distress and hostility in the experimental group (compared with
      controls) were observed after 1 year (p < .05). By 5 years, improvements in
      hostility tended to be maintained relative to the control group, but reductions
      in psychological distress were reported only by experimental patients with very
      high 5-year program adherence. Improvements in diet were related to weight
      reduction and decreases in percent diameter stenosis, and improvements in stress
      management were related to decreases in percent diameter stenosis at both follow
      ups (all p < .05). CONCLUSION: These findings illustrate the importance of
      targeting multiple health behaviors in secondary prevention of coronary heart
      disease.

PMID- 18823186
TI  - Social support from family and friends as a buffer of low spousal support among
      mothers of critically ill children: A multilevel modeling approach.
AB  - OBJECTIVE: To investigate whether social support from family and friends
      (family/friend support) attenuated ("buffered") adverse effects of having low
      spouse support (spousal support) among mothers of children undergoing
      hematopoietic stem cell transplantation (HSCT). DESIGN: One hundred sixty-three
      married mothers who were their child's primary caregiver during treatment
      completed assessments during the child's hospitalization for HSCT and 3-, 6-, and
      12-months post-HSCT. MEASURES: Family/friend support and spousal support were
      assessed during hospitalization. Maternal physical and mental health-related
      functioning (the main outcome measures) were assessed at all timepoints. RESULTS:
      Multilevel modeling was used to analyze trajectories of maternal functioning.
      Findings indicated that mothers with low spousal support and low family/friend
      support demonstrated the worst functioning across all timepoints. Mothers with
      low spousal support and high family/friend support demonstrated significantly
      better functioning, supporting the hypothesized buffering effect. Their
      functioning compared to the functioning of mothers with high spousal support.
      Moreover, mothers with high family/friend support demonstrated trajectories of
      physical health-related functioning that were more stable than the trajectories
      of mothers with low family/friend support. CONCLUSION: These findings have
      clinical implications in addition to advancing knowledge of social support
      processes among couples coping with the shared stressor of a child's life
      threatening illness and treatment.

PMID- 18823187
TI  - Pregnancy-specific stress, prenatal health behaviors, and birth outcomes.
AB  - OBJECTIVE: Stress in pregnancy predicts earlier birth and lower birth weight. The
      authors investigated whether pregnancy-specific stress contributes uniquely to
      birth outcomes compared with general stress, and whether prenatal health
      behaviors explain this association. DESIGN: Three structured prenatal interviews
      (N = 279) assessing state anxiety, perceived stress, life events, pregnancy
      specific stress, and health behaviors. MAIN OUTCOME MEASURES: Gestational age at
      delivery, birth weight, preterm delivery (<37 weeks), and low birth weight
      (<2,500 g). RESULTS: A latent pregnancy-specific stress factor predicted birth
      outcomes better than latent factors representing state anxiety, perceived stress,
      or life event stress, and than a latent factor constructed from all stress
      measures. Controlling for obstetric risk, pregnancy-specific stress was
      associated with smoking, caffeine consumption, and unhealthy eating, and
      inversely associated with healthy eating, vitamin use, exercise, and gestational
      age at delivery. Cigarette smoking predicted lower birth weight. Clinically
      defined birth outcomes were predicted by cigarette smoking and pregnancy-specific
      stress. CONCLUSION: Pregnancy-specific stress contributed directly to preterm
      delivery and indirectly to low birth weight through its association with smoking.
      Pregnancy-specific stress may be a more powerful contributor to birth outcomes
      than general stress.

PMID- 18823188
TI  - Effects of relationship maintenance on psychological distress and dyadic
      adjustment among couples coping with lung cancer.
AB  - OBJECTIVE: Relationship maintenance strategies help to ensure the continuation of
      valued relationships by keeping them at a certain level of intimacy. This study
      evaluated how lung cancer patients' and spouses' efforts to maintain their
      relationships affected their psychological and marital adjustment over time.
      DESIGN: Psychosocial questionnaires were administered within 1 month of lung
      cancer treatment initiation (baseline) and 3 and 6 months later to 158 lung
      cancer patients and their spouses. MAIN OUTCOME MEASURES: Study outcomes were
      global severity index scores on the Brief Symptom Inventory, and total scores on
      the Dyadic Adjustment Scale. RESULTS: Multilevel modeling analyses using the
      Actor-Partner Interdependence Model showed that, regardless of gender or social
      role (i.e., patient or spouse), individuals who engaged in the strategies of
      positivity, networks, and shared tasks reported less distress at baseline than
      other participants. Over time, the effects of providing more assurances and
      experiencing a partner's increased reliance on social networks differed: patient
      distress was exacerbated, and spouse distress was alleviated. Couples where both
      partners engaged in more frequent maintenance behaviors reported greater dyadic
      adjustment at baseline and over time. CONCLUSION: For couples coping with lung
      cancer, the initial treatment period may be an important time that sets the tone
      for future spousal interactions. Engaging in relationship maintenance during this
      stressful time may help mold more resilient relationships and facilitate
      adjustment as the disease progresses.

PMID- 18823189
TI  - The temporal relationship between alcohol consumption and HIV-medication
      adherence: a multilevel model of direct and moderating effects.
AB  - Previous studies documenting an association between alcohol use and HIV
      medication nonadherence, have been unable to distinguish between-persons
      characteristics from within-person characteristics representing the temporally
      linked effects of alcohol. Hierarchical Linear Modeling (HLM) explored within-
      and between-person predictors of adherence during the past 14 days, as well as
      factors that moderate the event-level effects of alcohol consumption among 272
      HIV-positive men and women with alcohol problems. On days in which participants
      drank, they had almost 9 times higher odds of medication nonadherence, with each
      drink increasing the odds by 20%. The cognitive and alcohol factors had
      significant between-person effects on adherence. Individuals with strong and
      rigid beliefs about the importance of strict medication adherence were
      significantly more affected by each dose of alcohol, while individuals with more
      alcohol use and problems were less affected by each drink. Regimen complexity
      increased the effects of having 1 or more drinks. These results highlight the
      importance of promoting medication adherence among alcohol-using adults,
      especially among patients with complex regimens or with high confidence and
      positive attitudes toward HIV medication.

PMID- 18823190
TI  - Beyond the most willing audiences: a meta-intervention to increase exposure to
      HIV-prevention programs by vulnerable populations.
AB  - OBJECTIVE: Enrollment in HIV-prevention interventions is more likely when the
      audience has safer rather than riskier HIV-relevant behavior. Thus, a meta
      intervention was designed to increase participation by an audience of infrequent
      condom users in Florida. DESIGN: Participants (N = 400) were randomly assigned to
      1 of 4 conditions varying the introduction to a counseling program. In the
      experimental condition, participants were told that the intervention gave
      participants options but might not change their behavior. In a standard
      introduction condition, participants were told that the program was highly
      effective at changing participants' behaviors. There was also an information
      control group containing a description of the program, and a no-information
      control group solely containing an invitation. MAIN OUTCOME MEASURES: The outcome
      measure was actual participation in the offered counseling. RESULTS: Findings
      indicated that the experimental introduction was the most successful at yielding
      participation in the counseling program when the audience had low intentions to
      use condoms in the future. CONCLUSION: Intervention introductions countering
      participants' resistance to change increase participation in HIV-prevention
      counseling among reluctant clients. Other meta-interventions may be explored to
      systematically augment the effectiveness of evidence-based health-promotion
      interventions.

PMID- 18823191
TI  - Effects of anger suppression on pain severity and pain behaviors among chronic
      pain patients: evaluation of an ironic process model.
AB  - OBJECTIVE: Evidence for links between anger inhibition or suppression and chronic
      pain severity is based mostly on studies with correlation designs. Following from
      ironic process theory, we proposed that attempts to suppress angry thoughts
      during provocation would increase subsequent pain intensity among chronic low
      back pain (CLBP) patients, and do so through paradoxically enhanced accessibility
      of anger. DESIGN: CLBP patients (N = 58) were assigned to suppression and
      nonsuppression conditions while performing a computer maze task with a harassing
      confederate. A structured pain behavior task (SPBT) followed. MAIN OUTCOME
      MEASURES: Self-reported anger, anxiety, and sadness following maze task. Self
      reported pain severity and number of observed pain behaviors during SPBT.
      RESULTS: Patients told to suppress during provocation: (a) reported greater anger
      following the maze task, reported greater pain intensity during the SPBT, and
      exhibited more pain behaviors than patients not suppressing; (b) postmaze anger
      levels significantly mediated group differences on pain behaviors. CONCLUSION:
      Attempts by CLBP patients to suppress anger may aggravate pain related to their
      clinical condition through ironically increased feelings of anger.

PMID- 18823192
TI  - Mispredicting and misremembering: patients with renal failure overestimate
      improvements in quality of life after a kidney transplant.
AB  - OBJECTIVE: People tend to overestimate the impact that future events will have on
      their quality of life. In the case of a medical treatment like kidney transplant,
      this should result in biased predictions--overestimates of how much the
      transplant will benefit quality of life. The authors surveyed kidney transplant
      patients, both before and after transplant, to test whether they would
      overestimate the benefits of a successful transplant for their quality of life.
      DESIGN: The authors interviewed 307 patients on a waiting list for cadaveric
      renal or renal-pancreatic transplant, and 195 patients one year after a
      successful transplant. A sub sample of patients were interviewed both before and
      after transplant. MAIN OUTCOME MEASURES: The survey included measures of quality
      of life, both in terms of an overall estimate (0-100), and across sub domains,
      including health, employment, and travel. RESULTS: Cross-sectional results
      suggested that overall quality of life improved after transplant, but the
      predictions of pretransplant patients overestimated the magnitude of the
      improvement (p < .01). In addition, patients predicted large improvements in
      specific life domains that did not change. These results were confirmed in
      longitudinal, prospective analyses. Additional analyses showed that
      posttransplant patients recalled their pretransplant quality of life to be much
      lower than what they had reported at the time. CONCLUSION: Consistent with an
      impact bias, patients substantially overestimated the benefits of a successful
      kidney transplant, both in terms of predictions of life after treatment, and in
      their memories of QOL before the transplant.

PMID- 18823193
TI  - Psychological resilience and dysfunction among hospitalized survivors of the SARS
      epidemic in Hong Kong: a latent class approach.
AB  - OBJECTIVE: To examine trajectories of psychological functioning using latent
      class analysis on a sample of hospitalized survivors of the 2003 severe acute
      respiratory syndrome (SARS) epidemic in Hong Kong. DESIGN: A longitudinal study
      of 997 survivors, recruited from among 1,331 individuals hospitalized for SARS,
      were interviewed at 6, 12, and 18 months after hospitalization. MAIN OUTCOME
      MEASURES: Psychological and physical functioning at each time point was measured
      using the 12-item Medical Outcome Study Short-Form Health Survey (SF-12).
      RESULTS: Four latent classes were identified--chronic dysfunction, delayed
      dysfunction, recovery, and resilience. All groups had better physical health than
      the chronic group. Resilient and recovered individuals had greater social support
      and less SARS-related worry, and resilient individuals were more likely to be
      male. The resilient group also had greater social support than the delayed group
      and better physical functioning than the recovered group. CONCLUSION: This study
      demonstrated that longitudinal outcome trajectories following a major health
      threat event in an Asian sample bear close resemblance to prototypical
      trajectories observed in trauma studies using Western samples. Unique predictors
      of the trajectories included factors observed in previous studies, such as social
      support, as well as factors of particular relevance to a major disease outbreak,
      such as SARS-related worry.

PMID- 18823194
TI  - Pip and pop: nonspatial auditory signals improve spatial visual search.
AB  - Searching for an object within a cluttered, continuously changing environment can
      be a very time-consuming process. The authors show that a simple auditory pip
      drastically decreases search times for a synchronized visual object that is
      normally very difficult to find. This effect occurs even though the pip contains
      no information on the location or identity of the visual object. The experiments
      also show that the effect is not due to general alerting (because it does not
      occur with visual cues), nor is it due to top-down cuing of the visual change
      (because it still occurs when the pip is synchronized with distractors on the
      majority of trials). Instead, we propose that the temporal information of the
      auditory signal is integrated with the visual signal, generating a relatively
      salient emergent feature that automatically draws attention. Phenomenally, the
      synchronous pip makes the visual object pop out from its complex environment,
      providing a direct demonstration of spatially nonspecific sounds affecting
      competition in spatial visual processing.

PMID- 18823195
TI  - Four-dimensional spatial reasoning in humans.
AB  - Human subjects practiced navigation in a virtual, computer-generated maze that
      contained 4 spatial dimensions rather than the usual 3. The subjects were able to
      learn the spatial geometry of the 4-dimensional maze as measured by their ability
      to perform path integration, a standard test of spatial ability. They were able
      to travel down a winding corridor to its end and then point back accurately
      toward the occluded origin. One interpretation is that the brain substrate for
      spatial navigation is not a built-in map of the 3-dimensional world. Instead it
      may be better described as a set of general rules for manipulating spatial
      information that can be applied with practice to a diversity of spatial
      frameworks.

PMID- 18823196
TI  - Load induced blindness.
AB  - Although the perceptual load theory of attention has stimulated a great deal of
      research, evidence for the role of perceptual load in determining perception has
      typically relied on indirect measures that infer perception from distractor
      effects on reaction times or neural activity (see N. Lavie, 2005, for a review).
      Here we varied the level of perceptual load in a letter-search task and assessed
      its effect on the conscious perception of a search-irrelevant shape stimulus
      appearing in the periphery, using a direct measure of awareness (present/absent
      reports). Detection sensitivity (d') was consistently reduced with high, compared
      to low, perceptual load but was unaffected by the level of working memory load.
      Because alternative accounts in terms of expectation, memory, response bias, and
      goal-neglect due to the more strenuous high load task were ruled out, these
      experiments clearly demonstrate that high perceptual load determines conscious
      perception, impairing the ability to merely detect the presence of a stimulus--a
      phenomenon of load induced blindness.

PMID- 18823197
TI  - Attention set for number: expectation and perceptual load in inattentional
      blindness.
AB  - Inattentional blindness is the failure to detect unexpected events when attention
      is otherwise engaged. Previous research indicates that inattentional blindness
      increases as perceptual demands intensify. The authors present 6 cuing
      experiments that manipulated both the perceptual demands of a primary letter
      naming task and the expectations of the individual. Inattentional blindness was
      greatest for individuals who held a numerical expectation that was consistent
      with the number of primary-task items presented. Expectation also affected
      detection differentially at various levels of perceptual load: Detection at
      moderate and high perceptual load was significantly affected by expectation,
      whereas detection at low perceptual load was not. The authors suggest that at
      moderate to high levels of perceptual load, individuals whose numerical
      expectations are fulfilled terminate processing when the primary task is
      complete, at the expense of the unexpected visual event. These experiments
      provide compelling evidence that expectations do affect detection of an
      unexpected stimulus, and they are the first to demonstrate that individuals set
      their attention for the number of items to be detected and are vulnerable to
      inattentional blindness whenever their primary-task numerical expectation is
      fulfilled.

PMID- 18823198
TI  - Object substitution masking: when does mask preview work?
AB  - When a target is enclosed by a 4-dot mask that persists after the target
      disappears, target identification is worse than it is when the mask terminates
      with the target. This masking effect is attributed to object substitution masking
      (OSM). Previewing the mask, however, attenuates OSM. This study investigated
      specific conditions under which mask preview was, or was not, effective in
      attenuating masking. In Experiment 1, the interstimulus interval (ISI) between
      previewed mask offset and target presentation was manipulated. The basic preview
      effect was replicated; neither ISI nor preview duration influenced target
      identification performance. In Experiment 2, mask configurations were
      manipulated. When the mask configuration at preview matched that at target
      presentation, the preview effect was replicated. New evidence of ineffective mask
      preview was found: When the two configurations did not match, performance
      declined. Yet, when the ISI between previewed mask offset and target presentation
      was removed such that the mask underwent apparent motion, preview was effective
      despite the configuration mismatch. An interpretation based on object
      representations provides an excellent account of these data.

PMID- 18823199
TI  - Effects of temporal integration on the shape of visual backward masking
      functions.
AB  - Many studies of cognition and perception use a visual mask to explore the
      dynamics of information processing of a target. Especially important in these
      applications is the time between the target and mask stimuli. A plot of some
      measure of target visibility against stimulus onset asynchrony is called a
      masking function, which can sometimes be monotonic increasing but other times is
      U-shaped. Theories of backward masking have long hypothesized that temporal
      integration of the target and mask influences properties of masking but have not
      connected the influence of integration with the shape of the masking function.
      With two experiments that vary the spatial properties of the target and mask, the
      authors provide evidence that temporal integration of the stimuli plays a
      critical role in determining the shape of the masking function. The resulting
      data both challenge current theories of backward masking and indicate what
      changes to the theories are needed to account for the new data. The authors
      further discuss the implication of the findings for uses of backward masking to
      explore other aspects of cognition.

PMID- 18823200
TI  - The effects of face inversion on the perception of long-range and local spatial
      relations in eye and mouth configuration.
AB  - A recent study hypothesized a configurational anisotropy in the face inversion
      effect, with vertical relations more difficult to process. However, another
      difference in the stimuli of that report was that the vertical but not horizontal
      shifts lacked local spatial references. Difficulty processing long-range spatial
      relations might also be predicted from a relevance-interaction explanation, which
      proposes that in inverted faces, spatial relations are processed efficiently only
      within high-relevance local regions. The authors performed 2 experiments to
      distinguish between these hypotheses. Experiment 1 showed that the inversion
      effect for vertical shifts of the eyes alone was more similar to that for
      horizontal eye shifts than for vertical shifts of the eyes and eyebrows. In
      Experiment 2, focused attention reduced the inversion effect for vertical mouth
      position more than that for vertical shifts of the eyes and brows. The authors
      concluded that face inversion impairs the perception of both local spatial
      relations in low-relevance regions and long-range spatial relations extending
      across multiple facial regions, consistent with a loss of efficient whole-face
      processing of the spatial relations between features.

PMID- 18823201
TI  - An action sequence withheld in memory can delay execution of visually guided
      actions: the generalization of response compatibility interference.
AB  - Withholding an action plan in memory for later execution can delay execution of
      another action, if the actions share a similar (compatible) action feature (i.e.,
      response hand). This phenomenon, termed compatibility interference (CI), was
      found for identity-based actions that do not require visual guidance. The authors
      examined whether CI can generalize to both identity-based and location-based
      actions that require visual guidance. Participants withheld a planned action
      based on the identity of a stimulus and then immediately executed a visually
      guided action (touch response) to a 2nd stimulus based on its color identity
      (Experiment 1), its spatial location (Experiment 2), or an intrinsic spatial
      location within an object (Experiment 3). Results showed CI for both left- and
      right-hand responses in Experiment 1. However, CI occurred for left- but not
      right-hand responses in Experiment 2 and 3. This suggests that CI can generalize
      to visually guided actions under cognitive control but not to actions that invoke
      automatic visual-control mechanisms where the left hemisphere may play a special
      role (C. Gonzalez, T. Ganel, & M. Goodale, 2006). The code occupation account for
      CI (G. Stoet & B. Hommel, 2002) is also discussed.

PMID- 18823202
TI  - Active gaze, visual look-ahead, and locomotor control.
AB  - The authors examined observers steering through a series of obstacles to
      determine the role of active gaze in shaping locomotor trajectories. Participants
      sat on a bicycle trainer integrated with a large field-of-view simulator and
      steered through a series of slalom gates. Steering behavior was determined by
      examining the passing distance through gates and the smoothness of trajectory.
      Gaze monitoring revealed which slalom targets were fixated and for how long.
      Participants tended to track the most immediate gate until it was about 1.5 s
      away, at which point gaze switched to the next slalom gate. To probe this gaze
      pattern, the authors then introduced a number of experimental conditions that
      placed spatial or temporal constraints on where participants could look and when.
      These manipulations resulted in systematic steering errors when observers were
      forced to use unnatural looking patterns, but errors were reduced when peripheral
      monitoring of obstacles was allowed. A steering model based on active gaze
      sampling is proposed, informed by the experimental conditions and consistent with
      observations in free-gaze experiments and with recommendations from real-world
      high-speed steering.

PMID- 18823203
TI  - Selective attention and control of action: comparative psychology of an
      artificial, evolved agent and people.
AB  - This study examined the selective attention abilities of a simple, artificial,
      evolved agent and considered implications of the agent's performance for theories
      of selective attention and action. The agent processed two targets in continuous
      time, catching one and then the other. This task required many cognitive
      operations, including prioritizing the first target (T1) over the second (T2);
      selectively focusing responses on T1, while preventing T2 from interfering with
      responses; creating a memory for the unselected T2 item, so that it could be
      efficiently processed later; and reallocating processing towards T2 after
      catching T1. The evolved agent demonstrated all these abilities. Analysis shows
      that the agent used reactive inhibition to selectively focus behavior. That is,
      the more salient T2, the more strongly responses towards T2 were inhibited and
      the slower the agent was to subsequently reallocate processing towards T2.
      Reactive inhibition was also suggested in two experiments with people, performing
      a virtually identical catch task. The presence of reactive inhibition in the
      simple agent and in people suggests that it is an important mechanism for
      selective processing.

PMID- 18823204
TI  - Impairments in the perception of odor-induced tastes and their relationship to
      impairments in taste perception.
AB  - Certain odors have tastelike qualities when sniffed. To the extent that these
      qualities are akin to real taste experiences, impairment in perception of odor
      induced tastes should be accompanied by taste impairment, and vice versa. Twelve
      patients were selected with possible odor-induced taste impairments or general
      taste impairments via a screening test, along with a further 6 patients with a
      probable taste impairment (insular lesion). These 18 patients, along with 19
      normal controls, completed a battery of odor, taste, visual control, and
      neuropsychological tests to assess impairments in odor-induced taste perception
      and general taste perception. Four patients had an odor-induced taste impairment
      and were also impaired on taste perception. A further analysis, using regression
      on the whole sample, indicated that taste impairments were associated with odor
      induced taste abnormalities independent of other predictors. This pattern also
      held for the patient group alone. The insular patients also exhibited both taste
      and odor-induced taste impairments. This study is the first to demonstrate a
      relationship between impaired taste perception and the perception of odor-induced
      tastes and suggests that both may rely on certain common neural substrates.

PMID- 18823205
TI  - The role of response repetition in task switching.
AB  - When switching between tasks, participants are sometimes required to use
      different response sets for each task. Thus, task switch and response set switch
      are confounded. In 5 experiments, the authors examined transitions of response
      within a linear 4-finger arrangement. A random baseline condition was compared
      with the cuing of specific response subsets grouped by hand or by finger
      equivalence, and these subsets were examined in both single task and task
      switching designs. Results showed that part of the task switch cost is associated
      with switching between response sets. Furthermore, the analysis revealed a novel
      effect: When task switching and repetition trials are mixed, a bias towards
      switching the response and/or hand is found in task repetition trials. Response
      repetition is hindered when a task switch is expected, even for those trials when
      a switch of task does not occur. The results demonstrate executive processes
      involved in task set configuration closely depend on the motoric processing of
      the response set. The results are also important for current theories of task set
      control.

PMID- 18823206
TI  - How to stop and change a response: the role of goal activation in multitasking.
AB  - Multitasking was studied in the stop-change paradigm, in which the response for a
      primary GO1 task had to be stopped and replaced by a response for a secondary GO2
      task on some trials. In 2 experiments, the delay between the stop signal and the
      change signal was manipulated to determine which task goals (GO1, GO2, or STOP)
      were involved in performance and to determine whether the goals were activated in
      series or in parallel. As the delay increased, the probability of responding on
      stop trials changed very little, but GO2 task reaction times decreased
      substantially. Such effects are consistent with both a nondeterministic serial
      model (in which the GO1 goal is replaced by the STOP goal, which is subsequently
      replaced by the GO2 goal) and a limited-capacity parallel model (in which
      stopping and GO2 processing occur concurrently) with a capacity-sharing
      proportion that resembles serial processing.

PMID- 18823207
TI  - Long-term aftereffects of response inhibition: memory retrieval, task goals, and
      cognitive control.
AB  - Cognitive control theories attribute control to executive processes that adjust
      and control behavior online. Theories of automaticity attribute control to memory
      retrieval. In the present study, online adjustments and memory retrieval were
      examined, and their roles in controlling performance in the stop-signal paradigm
      were elucidated. There was evidence of short-term response time adjustments after
      unsuccessful stopping. In addition, it was found that memory retrieval can slow
      responses for 1-20 trials after successful inhibition, which suggests the
      automatic retrieval of task goals. On the basis of these findings, the authors
      concluded that cognitive control can rely on both memory retrieval and executive
      processes.

PMID- 18823208
TI  - Masked priming with orthographic neighbors: a test of the lexical competition
      assumption.
AB  - In models of visual word identification that incorporate inhibitory competition
      among activated lexical units, a word's higher frequency neighbors will be the
      word's strongest competitors. Preactivation of these neighbors by a prime is
      predicted to delay the word's identification. Using the masked priming paradigm
      (K. I. Forster & C. Davis, 1984, J. Segui and J. Grainger (1990) reported that,
      consistent with this prediction, a higher frequency neighbor prime delayed the
      responses to a lower frequency target, whereas a lower frequency neighbor prime
      did not delay the responses to a higher frequency target. In the present
      experiments, using English stimuli, it was found that this pattern held only when
      the primes and targets had few neighbors; when the primes and targets had many
      neighbors, lower frequency primes delayed responses to higher frequency targets
      essentially as much as higher frequency primes delayed responses to lower
      frequency targets. Several possible explanations for these findings are discussed
      along with their theoretical implications. Considered together, the results are
      most consistent with activation-based accounts of the masked priming effect.

PMID- 18823209
TI  - Eye movements when reading transposed text: the importance of word-beginning
      letters.
AB  - Participants' eye movements were recorded as they read sentences with words
      containing transposed adjacent letters. Transpositions were either external
      (e.g., problme, rpoblem) or internal (e.g., porblem, probelm) and at either the
      beginning (e.g., rpoblem, porblem) or end (e.g., problme, probelm) of words. The
      results showed disruption for words with transposed letters compared to the
      normal baseline condition, and the greatest disruption was observed for word
      initial transpositions. In Experiment 1, transpositions within low frequency
      words led to longer reading times than when letters were transposed within high
      frequency words. Experiment 2 demonstrated that the position of word-initial
      letters is most critical even when parafoveal preview of words to the right of
      fixation is unavailable. The findings have important implications for the roles
      of different letter positions in word recognition and the effects of parafoveal
      preview on word recognition processes.

PMID- 18823210
TI  - Reading spaced and unspaced Chinese text: evidence from eye movements.
AB  - Native Chinese readers' eye movements were monitored as they read text that did
      or did not demark word boundary information. In Experiment 1, sentences had 4
      types of spacing: normal unspaced text, text with spaces between words, text with
      spaces between characters that yielded nonwords, and finally text with spaces
      between every character. The authors investigated whether the introduction of
      spaces into unspaced Chinese text facilitates reading and whether the word or,
      alternatively, the character is a unit of information that is of primary
      importance in Chinese reading. Global and local measures indicated that sentences
      with unfamiliar word spaced format were as easy to read as visually familiar
      unspaced text. Nonword spacing and a space between every character produced
      longer reading times. In Experiment 2, highlighting was used to create analogous
      conditions: normal Chinese text, highlighting that marked words, highlighting
      that yielded nonwords, and highlighting that marked each character. The data from
      both experiments clearly indicated that words, and not individual characters, are
      the unit of primary importance in Chinese reading.

PMID- 18823211
TI  - Retraction of Lozano, Hard and Tversky (2006).

PMID- 18823212
TI  - Are phonological representations of printed and spoken language isomorphic?
      Evidence from the restrictions on unattested onsets.
AB  - Are the phonological representations of printed and spoken words isomorphic? This
      question is addressed by investigating the restrictions on onsets. Cross
      linguistic research suggests that onsets of rising sonority are preferred to
      sonority plateaus, which, in turn, are preferred to sonority falls (e.g., bnif
      [symbol: see text] bdif [symbol: see text] lbif). Of interest is whether these
      grammatical preferences constrain the recognition of auditory and printed words
      by speakers of English--a language in which such onsets are unattested. Five
      experiments compare phonological lexical decision responses to nonwords,
      including unattested onsets, through either aural or visual presentation. Results
      suggest that both hearers and readers are sensitive to the phonotactics of
      unattested onsets. However, the phonotactic generalizations of hearers and
      readers differ on their scope and source. Hearers differentiated all three types
      of onsets (e.g., bnif, bdif, and lbif), and their behavior implicated both
      grammatical and statistical constraints. In contrast, readers were able to
      differentiate only those structures similar to attested English onsets from
      dissimilar structures (i.e., bnif vs. bdif or lbif), and their preferences
      reflected statistical knowledge alone. These findings suggest that the
      phonological representations informing lexical decision to spoken and printed
      words are not isomorphic.

PMID- 18823213
TI  - Category and perceptual interference in second-language phoneme learning: an
      examination of English /w/-/v/ learning by Sinhala, German, and Dutch speakers.
AB  - The present study investigated the perception and production of English /w/ and
      /v/ by native speakers of Sinhala, German, and Dutch, with the aim of examining
      how their native language phonetic processing affected the acquisition of these
      phonemes. Subjects performed a battery of tests that assessed their
      identification accuracy for natural recordings, their degree of spoken accent,
      their relative use of place and manner cues, the assimilation of these phonemes
      into native-language categories, and their perceptual maps (i.e.,
      multidimensional scaling solutions) for these phonemes. Most Sinhala speakers had
      near-chance identification accuracy, Germans ranged from chance to 100% correct,
      and Dutch speakers had uniformly high accuracy. The results suggest that these
      learning differences were caused more by perceptual interference than by category
      assimilation; Sinhala and German speakers both have a single native-language
      phoneme that is similar to English /w/ and /v/, but the auditory sensitivities of
      Sinhala speakers make it harder for them to discern the acoustic cues that are
      critical to /w/-/v/ categorization.

PMID- 18823214
TI  - Improving accuracy in detecting acoustic onsets.
AB  - In current cognitive psychology, naming latencies are commonly measured by
      electronic voice keys that detect when sound exceeds a certain amplitude
      threshold. However, recent research (e.g., K. Rastle & M. H. Davis, 2002) has
      shown that these devices are particularly inaccurate in precisely detecting
      acoustic onsets. In this article, the authors discuss the various problems and
      solutions that have been put forward with respect to this issue and show that
      classical voice keys may trigger several tens of milliseconds later than acoustic
      onset. The authors argue that a solution to this problem may come from voice keys
      that use a combination of analogue and digital noise (nonspeech sound) detection.
      It is shown that the acoustic onsets detected by such a device are only a few
      milliseconds delayed and correlate highly (up to .99) with reaction time values
      obtained by visual waveform inspection.

PMID- 18823215
TI  - Effect of intravenous propacetamol on blood pressure in febrile critically ill
      patients.
AB  - STUDY OBJECTIVES: To investigate the effect of intravenous propacetamol, a
      parenteral bioprecursor of acetaminophen, on systemic blood pressure in
      critically ill patients with fever, and to establish the prevalence and clinical
      significance of this effect. DESIGN: Prospective, observational study. SETTING: A
      six-bed medical-surgical intensive care unit (ICU) of a university-affiliated
      tertiary care hospital in Israel. PATIENTS: Fourteen critically ill patients
      (aged 17-83 yrs) with sepsis and fever (body temperature > or = 38 degrees C) who
      received an intravenous infusion of propacetamol 2 g over 15-20 minutes every 6
      hours as needed to reduce fever. MEASUREMENTS AND RESULTS: Demographic data,
      including degree of sepsis, were collected at baseline (before propacetamol
      infusion). Blood pressure, heart rate, body temperature, and need for fluid or
      vasopressor therapy were recorded at baseline, at end of infusion, and at 15, 30,
      45, 60, 90, and 120 minutes after propacetamol administration. The drug was
      administered on 72 occasions in the 14 patients. Mean +/- SE systolic, diastolic,
      and mean arterial pressures recorded 15 minutes after propacetamol administration
      were significantly lower than baseline measurements: 123 +/- 29 versus 148 +/-
      33, 62 +/- 12 versus 70 +/- 15, and 83 +/- 16 versus 97 +/- 19 mm Hg,
      respectively (p<0.05). In 24 (33%) of the 72 infusions, systolic blood pressure
      decreased to below 90 mm Hg and required intervention with fluid bolus
      administration on six occasions; a fluid bolus was accompanied by a dosage
      increase or initiation of a norepinephrine infusion on 18 occasions. No
      correlation, however, was noted between the degree of decrease in mean arterial
      pressure and decrease in temperature (r(2)=0.01), or the degree of decrease in
      mean arterial pressure and decrease in heart rate (r2=0.23), at each data
      collection time point, as measured by linear regression. CONCLUSION: Intravenous
      propacetamol, given in antipyretic doses, caused a significant decrease in blood
      pressure 15 minutes after administration in febrile critically ill patients. This
      drug-induced hypotension was clinically relevant in that interventions to control
      blood pressure were required. Thus, clinicians should be aware of this potential
      deleterious effect, particularly in specific populations such as critically ill
      patients.

PMID- 18823216
TI  - Overnight transition from carbamazepine to oxcarbazepine in children and
      adolescents.
AB  - STUDY OBJECTIVE: To evaluate our clinical experience in pediatric patients who
      were rapidly switched from carbamazepine to oxcarbazepine at full therapeutic
      doses. DESIGN: Retrospective medical record review. SETTING: Children's hospital.
      PATIENTS: Twenty six patients (mean age 9.8 yrs, range 5-21 yrs) with childhood
      epilepsy who were converted from carbamazepine to oxcarbazepine overnight between
      January 2003 and December 2005. MEASUREMENTS AND MAIN RESULTS: Data collection
      included patient demographics, seizure type, epilepsy syndrome, seizure
      frequency, and adverse events. Dose conversion ratios for switching from
      carbamazepine to oxcarbazepine ranged from 1:1-1.5. The transition was well
      tolerated, with only three patients experiencing an adverse event (rash). Among
      the other 23 patients, seizure frequency decreased in 12 (52%), increased in two
      (9%), and remained unchanged in nine (39%). CONCLUSION: Overnight switching from
      carbamazepine to oxcarbazepine may be a useful option for pediatric patients who
      cannot tolerate or whose condition is unresponsive to carbamazepine.

PMID- 18823217
TI  - Effects of different meal compositions and fasted state on the oral
      bioavailability of etravirine.
AB  - STUDY OBJECTIVE: To determine the effects of various meal compositions and the
      fasted state on the pharmacokinetics of etravirine, a nonnucleoside reverse
      transcriptase inhibitor. DESIGN: Phase I, open-label, randomized, repeated single
      dose, three-period crossover trial. SETTING: Clinical pharmacology unit.
      PARTICIPANTS: Two parallel panels of 12 human immunodeficiency virus (HIV)
      negative, healthy, male volunteers. Twenty volunteers completed the study; three
      withdrew consent, and one was lost to follow-up. Intervention. Panel 1 received a
      single dose of etravirine 100 mg after a standard breakfast, in the fasted state,
      and after a light breakfast (croissant). Panel 2 received the same treatment
      after a standard breakfast, after an enhanced-fiber breakfast, and after a high
      fat breakfast. Each treatment was separated by a washout period of at least 14
      days. MEASUREMENTS AND MAIN RESULTS: For each treatment, full pharmacokinetic
      profiles of etravirine were determined up to 96 hours after dosing.
      Pharmacokinetic parameters were determined by noncompartmental methods and
      analyzed using a linear mixed-effects model for a crossover design. The least
      squares mean ratio for the area under the plasma concentration-time curve from
      time of administration to the last time point with a measurable concentration
      after dosing (AUClast) was 0.49 (90% confidence interval [CI] 0.39-0.61) for the
      fasted state compared with dosing after a standard breakfast. When dosing
      occurred after a light or enhanced-fiber breakfast, the corresponding values were
      0.80 (90% CI 0.69-0.94) and 0.75 (90% CI 0.63-0.90), respectively. When
      administered after a high-fat breakfast the least-squares mean ratio of AUC(last)
      was 1.09 (0.84-1.41), compared with dosing after a standard breakfast. Adverse
      events were also assessed. Under all conditions, single doses of etravirine 100
      mg were generally safe and well tolerated. CONCLUSION: Administration of
      etravirine in a fasted state resulted in 51% lower mean exposure compared with
      dosing after a standard breakfast. Etravirine should be administered following a
      meal to improve bioavailability; however, differences in exposure after a
      standard breakfast versus a high-fat, enhanced-fiber, or light breakfast
      (croissant) were not considered clinically relevant.

PMID- 18823218
TI  - Pharmacokinetics of oral posaconazole in neutropenic patients receiving
      chemotherapy for acute myelogenous leukemia or myelodysplastic syndrome.
AB  - STUDY OBJECTIVE: To analyze the pharmacokinetics of posaconazole administered as
      prophylaxis for invasive fungal infection (IFI) in neutropenic patients receiving
      chemotherapy for acute myelogenous leukemia (AML) or myelodysplastic syndrome
      (MDS). DESIGN: Pharmacokinetic subanalysis of a phase III, prospective,
      randomized, multicenter, evaluator-blinded trial comparing posaconazole with
      standard azoles (fluconazole and itraconazole). PATIENTS: One hundred ninety-four
      patients with AML or MDS who received posaconazole oral suspension 200 mg 3
      times/day with meals or a nutritional supplement for a minimum of 7 days to
      achieve steady state and for a maximum of 12 weeks. INTERVENTION: For the first
      20 patients, blood samples were collected before the first dose on day 8 and at
      2, 4, 6, and 24 hours after that first dose; for all other patients, blood
      samples were collected at 1 and 3 hours after the first dose on day 8 and during
      the first episode of evaluation for a possible IFI. MEASUREMENTS AND MAIN
      RESULTS: The effects of the following covariates on average (Cav) and maximum
      (Cmax) posaconazole plasma concentrations at steady state were explored: age,
      sex, and race-ethnicity; proven or probable IFI; baseline body weight and body
      surface area; and baseline (on or before day 7) increases in liver enzyme levels,
      mucositis, neutropenia, diarrhea, vomiting, or use of an H2-receptor antagonist
      or proton pump inhibitor. Diarrhea, proton pump inhibitor use, gamma-glutamyl
      transferase level of 2 or more times the upper limit of normal, and race
      ethnicity reduced Cav. Although statistically significant, these results were not
      considered clinically significant and did not necessitate posaconazole dosage
      adjustments. Mean Cav and Cmax values did not appear different in the six
      patients with IFIs (three with proven IFIs, three with probable IFIs) compared
      with the entire sample of 194 patients; however, a definitive conclusion cannot
      be made due to the small sample size of patients with IFI. No factor found to
      affect posaconazole concentrations predominated in patients with IFIs.
      CONCLUSION: Oral posaconazole 200 mg 3 times/day provided plasma concentrations
      adequate for preventing IFIs. No dosage adjustments are recommended based on any
      covariate tested.

PMID- 18823219
TI  - Combination antiplatelet agents for secondary prevention of ischemic stroke.
AB  - Stroke is a leading cause of death and the primary cause of serious, long-term
      disability in the United States. Joint guidelines from the American Heart
      Association (AHA) and American Stroke Association (ASA), as well as recent
      guidelines from the Eighth American College of Chest Physicians (ACCP) Conference
      on Antithrombotic and Antiplatelet Therapy, recommend aspirin, clopidogrel, or
      extended-release dipyridamole plus aspirin as acceptable first-line options for
      secondary prevention of ischemic events in patients with a history of ischemic
      stroke or transient ischemic attack (TIA). The ACCP strongly recommends the
      combination of extended-release dipyridamole plus aspirin over aspirin
      monotherapy (highest level of evidence) and suggests clopidogrel monotherapy over
      aspirin monotherapy (lower level of evidence). The AHA-ASA guidelines suggest
      that either extended-release dipyridamole plus aspirin or clopidogrel monotherapy
      should be used over aspirin monotherapy. Both guidelines recommend avoiding the
      combination of clopidogrel and aspirin for most patients with previous stroke or
      TIA. Results from recent trials evaluating combination antiplatelet therapy have
      been published that enhance the AHA-ASA recommendations and provide the
      foundation for the updated ACCP guideline. To identify pertinent combination
      antiplatelet trials, a MEDLINE search of the literature from 1967-2007 was
      performed. Two trials were identified--the European-Australasian Stroke
      Prevention in Reversible Ischemia Trial (ESPRIT) and Clopidogrel for High
      Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance
      (CHARISMA). The ESPRIT compared aspirin monotherapy with the combination of
      aspirin plus extended-release dipyridamole for prevention of secondary ischemic
      events in patients with a history of TIA or minor stroke. The CHARISMA trial
      compared aspirin plus clopidogrel with aspirin alone in a population at high risk
      for atherothrombotic events using the composite outcome of myocardial infarction,
      stroke, and death from cardiovascular causes. Data from ESPRIT add to evidence
      that the combination of aspirin plus extended-release dipyridamole is superior to
      aspirin alone. The findings of the CHARISMA trial reinforce recommendations from
      both AHA-ASA and ACCP that the combination of aspirin and clopidogrel be reserved
      for special populations requiring this antiplatelet combination (e.g., those who
      have had coronary artery stenting).

PMID- 18823220
TI  - Treatment of extensively drug-resistant tuberculosis and role of the pharmacist.
AB  - Abstract Outbreaks of extensively drug-resistant tuberculosis (XDR-TB) in
      developing countries and recent headlines of an American traveling with a
      resistant variant of tuberculosis have brought XDR-TB into the spotlight. The
      World Health Organization and the United States Centers for Disease Control and
      Prevention have identified XDR-TB as a serious public health threat and are
      mandating increased efforts at control of tuberculosis. Although XDR-TB is
      believed to be no more infectious than other variants of tuberculosis, infection
      with and spread of XDR-TB are concerning because of the ineffectiveness,
      toxicity, and cost of the available tuberculosis treatment options. Pharmacists
      may not be aware of the recent trends in tuberculosis resistance or of the impact
      that they can have on educating the public about this disease. To gain a better
      understanding of this disease and the potential roles for pharmacists in public
      health awareness of tuberculosis and in the care of patients with and at risk for
      this disease, we undertook an extensive search of the Internet, including Web
      sites of tuberculosis advocacy groups, and of MEDLINE from January 1968-March
      2008. Currently, XDR-TB infection is uncommon in the United States, but if
      history is any indication, there is a high potential for an outbreak or epidemic.
      The XDR-TB variant has emerged from mismanaging multidrug-resistant tuberculosis,
      treating tuberculosis with too few drugs, using less effective second-line drugs,
      and not educating patients about the dangers of nonadherence. With only limited
      hopes of a novel effective drug combination regimen, use of available
      antimycobacterial drugs needs to be optimized. Pharmacists can be key players in
      the prevention and treatment of tuberculosis by promoting adherence, assessing
      patients for risk factors for resistant disease, providing information about
      disease control and prevention, and monitoring for effectiveness, adverse
      effects, and drug interactions.

PMID- 18823221
TI  - Lapatinib and ixabepilone for the treatment of metastatic breast cancer.
AB  - Breast cancer is the second leading cause of cancer death in women. Treatment
      options for advanced-stage disease, although numerous, remain suboptimal.
      Lapatinib and ixabepilone are two new agents approved by the United States Food
      and Drug Administration (FDA) in 2007 for the treatment of locally advanced
      breast cancer (LABC) or metastatic breast cancer (MBC). When added to the
      existing endocrine therapies-single--agent cytotoxic therapies and combination
      chemotherapy regimens--lapatinib and ixabepilone offer potential treatment
      strategies for disease that has become resistant to trastuzumab and the taxanes,
      respectively. Lapatinib is an oral dual tyrosine kinase inhibitor against members
      of the human epidermal growth factor receptor (HER) family (HER1 or epidermal
      growth factor receptor [EGFR], and HER2). It is indicated for combination therapy
      with capecitabine for the treatment of patients with HER2-overexpressing LABC or
      MBC whose disease has progressed after receiving previous treatment with an
      anthracycline, a taxane, and trastuzumab. Of note, lapatinib is the first FDA
      approved tyrosine kinase inhibitor indicated for use in MBC. Ixabepilone, the
      first FDA-approved analog of the antimicrotubule agent epothilone B, is indicated
      as monotherapy for the treatment of LABC or MBC in patients whose tumors are
      refractory or resistant to anthracyclines, taxanes, and capecitabine. It is also
      indicated in combination with capecitabine for treatment of LABC or MBC that is
      resistant to anthracycline and taxane. Both lapatinib and ixabepilone are fairly
      well tolerated. The most common toxicities with lapatinib are diarrhea (65%) and
      hand-and-foot syndrome (53%), whereas peripheral neuropathy (62%), fatigue (56%),
      and neutropenia (54%) are most common with ixabepilone. Though the conventional
      standard end point of overall survival has not yet been assessed in clinical
      trials, these agents have been shown to improve surrogate markers of clinical
      benefit: progression-free survival and the related time to progression. Future
      clinical trials should focus on elucidation of optimal combination or sequential
      therapies, as well as patient-specific therapies based on tumor characteristics,
      such as biomarkers and tumor subtypes.

PMID- 18823222
TI  - Anemia of critical illness.
AB  - Anemia of critical illness, a commonly encountered clinical situation, is
      hematologically similar to that of chronic anemia, except that the onset is
      generally sudden. The etiology is usually multifactorial, occurring as a
      consequence of direct inhibitory effects of inflammatory cytokines,
      erythropoietin deficiency, blunted erythropoietic response, blood loss,
      nutritional deficiencies, and renal insufficiency. Although anemia is not well
      tolerated by critically ill patients, aggressive treatment of anemia can be just
      as detrimental as no treatment. Different types of anemia may coexist in a
      patient in the intensive care unit, making diagnosis and differentiation among
      these anemias complex, therefore requiring good diagnostic skills. Although
      several therapeutic options are available to treat anemia, critically ill
      patients often receive a transfusion, and yet, most recent studies indicate that
      blood transfusions in critically ill patients are associated with worse outcomes,
      including higher morbidity and mortality. These studies have generated interest
      in the administration of exogenous erythropoietin and iron therapy.
      Unfortunately, the accurate determination of iron status can be a rather
      difficult task, an undertaking that is made even more difficult by the presence
      of comorbid conditions that can affect the commonly used parameters for guiding
      iron therapy. The use of erythropoiesis-stimulating agents is rapidly gaining
      acceptance, although they also present potential problems of their own.

PMID- 18823223
TI  - Paliperidone extended-release for the treatment of schizophrenia.
AB  - Paliperidone, the major active metabolite of risperidone (9-hydroxyrisperidone),
      is a second-generation antipsychotic that was recently approved by the United
      States Food and Drug Administration for treatment of acute schizophrenia and for
      maintenance treatment of schizophrenia. We performed a literature search of
      PreMEDLINE, MEDLINE, and International Pharmaceutical Abstracts from 1966-October
      2007 to review the available data on the pharmacology, pharmacokinetics, clinical
      evidence, and safety and tolerability profile of paliperidone extended-release
      (ER). Articles from randomized controlled trials, abstracts, and posters
      presented at national scientific meetings were included in this review.
      Paliperidone ER has been shown to be significantly more effective in improving
      schizophrenic symptoms according to the Positive and Negative Symptom Scale
      (PANSS), Clinical Global Impressions-Severity Scale, and Personal and Social
      Performance Scale compared with placebo (p<0.05). In addition, limited evidence
      suggests similar efficacy between paliperidone ER 6-12 mg/day and risperidone 4-6
      mg/day. A 2-week, double-blind comparison with quetiapine demonstrated that
      paliperidone ER was significantly better than quetiapine in improving PANSS
      scores (p<0.001). Paliperidone ER appears to be well tolerated at the recommended
      starting dosage of 6 mg/day. The most commonly reported adverse effect was dose
      related extrapyramidal symptoms. Weight gain and metabolic disturbances were
      minimal. The cost of paliperidone ER appears to be slightly higher than that of
      other second-generation antipsychotics. Paliperidone ER tablets may be a safe and
      effective treatment option for acute schizophrenia and maintenance treatment of
      schizophrenia compared with placebo. Because well-designed comparative data are
      lacking, an additional benefit over other antipsychotics is yet to be determined.

PMID- 18823224
TI  - Determining effective insulin analog therapy based on the individualized needs of
      patients with type 2 diabetes mellitus.
AB  - Abstract To manage patients with type 2 diabetes mellitus effectively and delay
      the onset of diabetes-related complications, therapeutic targets for glycemic
      control, as recommended by the American Diabetes Association and the American
      Association of Clinical Endocrinologists, should be implemented in clinical
      practice. Initiation of treatment with insulin is a critical step in achieving
      target glycemic levels. A variety of insulin formulations are available in the
      United States that can be matched to meet the diverse needs and lifestyles of
      patients with type 2 diabetes. In particular, insulin analogs have more
      predictable profiles of action and thus are able to more closely mimic
      physiologic insulin action. Case studies are presented to demonstrate the use of
      different types of insulin analogs in various situations as supported by data
      from clinical trials. The needs of the individual patient are considered in terms
      of his or her particular preferences, medical history, and adjustments for
      lifestyle concerns. The involvement of pharmacists in this individualized therapy
      is critical in order to enhance patients' understanding of their disease and
      their most effective treatment options.

PMID- 18823226
TI  - Development during adolescence of the neural processing of social emotion.
AB  - In this fMRI study, we investigated the development between adolescence and
      adulthood of the neural processing of social emotions. Unlike basic emotions
      (such as disgust and fear), social emotions (such as guilt and embarrassment)
      require the representation of another's mental states. Nineteen adolescents (10
      18 years) and 10 adults (22-32 years) were scanned while thinking about scenarios
      featuring either social or basic emotions. In both age groups, the anterior
      rostral medial prefrontal cortex (MPFC) was activated during social versus basic
      emotion. However, adolescents activated a lateral part of the MPFC for social
      versus basic emotions, whereas adults did not. Relative to adolescents, adults
      showed higher activity in the left temporal pole for social versus basic
      emotions. These results show that, although the MPFC is activated during social
      emotion in both adults and adolescents, adolescents recruit anterior (MPFC)
      regions more than do adults, and adults recruit posterior (temporal) regions more
      than do adolescents.

PMID- 18823227
TI  - Concurrent sound segregation is enhanced in musicians.
AB  - The ability to segregate simultaneously occurring sounds is fundamental to
      auditory perception. Many studies have shown that musicians have enhanced
      auditory perceptual abilities; however, the impact of musical expertise on
      segregating concurrently occurring sounds is unknown. Therefore, we examined
      whether long-term musical training can improve listeners' ability to segregate
      sounds that occur simultaneously. Participants were presented with complex sounds
      that had either all harmonics in tune or the second harmonic mistuned by 1%, 2%,
      4%, 8%, or 16% of its original value. The likelihood of hearing two sounds
      simultaneously increased with mistuning, and this effect was greater in musicians
      than nonmusicians. The segregation of the mistuned harmonic from the harmonic
      series was paralleled by an object-related negativity that was larger and peaked
      earlier in musicians. It also coincided with a late positive wave referred to as
      the P400 whose amplitude was larger in musicians than in nonmusicians. The
      behavioral and electrophysiological effects of musical expertise were specific to
      processing the mistuned harmonic as the N1, the N1c, and the P2 waves elicited by
      the tuned stimuli were comparable in both musicians and nonmusicians. These
      results demonstrate that listeners' ability to segregate concurrent sounds based
      on harmonicity is modulated by experience and provides a basis for further
      studies assessing the potential rehabilitative effects of musical training on
      solving complex scene analysis problems illustrated by the cocktail party
      example.

PMID- 18823228
TI  - The role of serotonin in nonnormative risky choice: the effects of tryptophan
      supplements on the "reflection effect" in healthy adult volunteers.
AB  - Risky decision-making involves weighing good and bad outcomes against their
      probabilities in order to determine the relative values of candidate actions.
      Although human decision-making sometimes conforms to rational models of how this
      weighting is achieved, irrational (or nonnormative) patterns of risky choice,
      including shifts between risk-averse and risk-seeking choices involving
      equivalent-value gambles (the "reflection effect"), are frequently observed. In
      the present experiment, we investigated the role of serotonin in decision-making
      under conditions of uncertainty. Fifteen healthy adult volunteers received a
      treatment of 3 g per day of the serotonin precursor, tryptophan, in the form of
      dietary supplements over a 14-day period, whereas 15 age- and IQ-matched control
      volunteers received a matched placebo substance. At test, all participants
      completed a risky decision-making task involving a series of choices between two
      simultaneously presented gambles, differing in the magnitude of their possible
      gains, the magnitude of their possible losses, and the probabilities with which
      these outcomes were delivered. Tryptophan supplements were associated with
      alterations in the weighting of gains and small losses perhaps reflecting reduced
      loss-aversion, and a marked and significant diminution of the reflection effect.
      We conclude that serotonin activity plays a significant role in nonnormative
      risky decision-making under conditions of uncertainty.

PMID- 18823229
TI  - Modality- and task-specific brain regions involved in Chinese lexical processing.
AB  - fMRI was used to examine lexical processing in native adult Chinese speakers. A 2
      task (semantics and phonology) x 2 modality (visual and auditory) within-subject
      design was adopted. The semantic task involved a meaning association judgment and
      the phonological task involved a rhyming judgment to two sequentially presented
      words. The overall effect across tasks and modalities was used to identify seven
      ROIs, including the left fusiform gyrus (FG), the left superior temporal gyrus
      (STG), the left ventral inferior frontal gyrus (VIFG), the left middle temporal
      gyrus (MTG), the left dorsal inferior frontal gyrus (DIFG), the left inferior
      parietal lobule (IPL), and the left middle frontal gyrus (MFG). ROI analyses
      revealed two modality-specific areas, FG for visual and STG for auditory, and
      three task-specific areas, IPL and DIFG for phonology and VIFG for semantics.
      Greater DIFG activation was associated with conflicting tonal information between
      words for the auditory rhyming task, suggesting this region's role in strategic
      phonological processing, and greater VIFG activation was correlated with lower
      association between words for both the auditory and the visual meaning task,
      suggesting this region's role in retrieval and selection of semantic
      representations. The modality- and task-specific effects in Chinese revealed by
      this study are similar to those found in alphabetical languages. Unlike English,
      we found that MFG was both modality- and task-specific, suggesting that MFG may
      be responsible for the visuospatial analysis of Chinese characters and
      orthography-to-phonology integration at a syllabic level.

PMID- 18823230
TI  - Neural correlates of metamemory: a comparison of feeling-of-knowing and
      retrospective confidence judgments.
AB  - Metamemory refers to knowledge and monitoring of one's own memory. Metamemory
      monitoring can be done prospectively with respect to subsequent memory retrieval
      or retrospectively with respect to previous memory retrieval. In this study, we
      used fMRI to compare neural activity during prospective feeling-of-knowing and
      retrospective confidence tasks in order to examine common and distinct mechanisms
      supporting multiple forms of metamemory monitoring. Both metamemory tasks,
      compared to non-metamemory tasks, were associated with greater activity in medial
      prefrontal, medial parietal, and lateral parietal regions, which have previously
      been implicated in internally directed cognition. Furthermore, compared to non
      metamemory tasks, metamemory tasks were associated with less activity in
      occipital regions, and in lateral inferior frontal and dorsal medial prefrontal
      regions, which have previously shown involvement in visual processing and
      stimulus-oriented attention, respectively. Thus, neural activity related to
      metamemory is characterized by both a shift toward internally directed cognition
      and away from externally directed cognition. Several regions demonstrated
      differences in neural activity between feeling-of-knowing and confidence tasks,
      including fusiform, medial temporal lobe, and medial parietal regions;
      furthermore, these regions also showed interaction effects between task and the
      subjective metamemory rating, suggesting that they are sensitive to the
      information monitored in each particular task. These findings demonstrate both
      common and distinct neural mechanisms supporting metamemory processes and also
      serve to elucidate the functional roles of previously characterized brain
      networks.

PMID- 18823231
TI  - The cerebral basis of mapping nonsymbolic numerical quantities onto abstract
      symbols: an fMRI training study.
AB  - Although significant insights into the neural basis of numerical and mathematical
      processing have been made, the neural processes that enable abstract symbols to
      become numerical remain largely unexplored in humans. In the present study, adult
      participants were trained to associate novel symbols with nonsymbolic numerical
      magnitudes (arrays of dots). Functional magnetic resonance imaging was used to
      examine the neural correlates of numerical comparison versus recognition of the
      novel symbols after each of two training stages. A left-lateralized fronto
      parietal network, including the intraparietal sulcus, the precuneus, and the
      dorsal prefrontal cortex, was more active during numerical comparison than during
      perceptual recognition. In contrast, a network including bilateral temporal
      occipital regions was more active during recognition than comparison. A whole
      brain three-way interaction revealed that those individuals who had higher scores
      on a postscan numerical task (measuring their understanding of the global
      numerical organization of the novel symbols) exhibited increasing segregation
      between the two tasks in the bilateral intraparietal sulci as a function of
      increased training. Furthermore, whole-brain regression analysis showed that
      activity in the left intraparietal sulcus was systematically related to the
      effect of numerical distance on accuracy. These data provide converging evidence
      that parietal and left prefrontal cortices are involved in learning to map
      numerical quantities onto visual symbols. Only the parietal cortex, however,
      appeared systematically related to the degree to which individuals learned to
      associate novel symbols with their numerical referents. We conclude that the left
      parietal cortex, in particular, may play a central role in imbuing visual symbols
      with numerical meaning.

PMID- 18823232
TI  - Mind your left: spatial bias in subcortical fear processing.
AB  - Hemispheric lateralization of emotional processing has long been suggested, but
      its underlying neural mechanisms have not yet been defined. In this functional
      magnetic resonance imaging study, facial expressions were presented to 10 right
      handed healthy adult females in an event-related visual half-field presentation
      paradigm. Differential activations to fearful versus neutral faces were observed
      in the amygdala, pulvinar, and superior colliculus only for faces presented in
      the left hemifield. Interestingly, the left hemifield advantage for fear
      processing was observed in both hemispheres. These results suggest a leftward
      bias in subcortical fear processing, consistent with the well-documented leftward
      bias of danger-associated behaviors in animals. The current finding highlights
      the importance of hemifield advantage in emotional lateralization, which might
      reflect the combination of hemispheric dominance and asymmetric interhemispheric
      information transfer.

PMID- 18823233
TI  - Neural systems supporting the control of affective and cognitive conflicts.
AB  - Although many studies have examined the neural bases of controlling cognitive
      responses, the neural systems for controlling conflicts between competing
      affective responses remain unclear. To address the neural correlates of affective
      conflict and their relationship to cognitive conflict, the present study
      collected whole-brain fMRI data during two versions of the Eriksen flanker task.
      For these tasks, participants indicated either the valence (affective task) or
      the semantic category (cognitive task) of a central target word while ignoring
      flanking words that mapped onto either the same (congruent) or a different
      (incongruent) response as the target. Overall, contrasts of incongruent >
      congruent trials showed that bilateral dorsal ACC, posterior medial frontal
      cortex, and dorsolateral pFC were active during both kinds of conflict, whereas
      rostral medial pFC and left ventrolateral pFC were differentially active during
      affective or cognitive conflict, respectively. Individual difference analyses
      showed that separate regions of rostral cingulate/ventromedial pFC and left
      ventrolateral pFC were positively correlated with the magnitude of response time
      interference. Taken together, the findings that controlling affective and
      cognitive conflicts depends upon both common and distinct systems have important
      implications for understanding the organization of control systems in general and
      their potential dysfunction in clinical disorders.

PMID- 18823235
TI  - Optimizing functional accuracy of TMS in cognitive studies: a comparison of
      methods.
AB  - Transcranial magnetic stimulation (TMS) is a tool for inducing transient
      disruptions of neural activity noninvasively in conscious human volunteers. In
      recent years, the investigative domain of TMS has expanded and now encompasses
      causal structure-function relationships across the whole gamut of cognitive
      functions and associated cortical brain regions. Consequently, the importance of
      how to determine the target stimulation site has increased and a number of
      alternative methods have emerged. Comparison across studies is precluded because
      different studies necessarily use different tasks, sites, TMS conditions, and
      have different goals. Here, therefore, we systematically compare four commonly
      used TMS coil positioning approaches by using them to induce behavioral change in
      a single cognitive study. Specifically, we investigated the behavioral impact of
      right parietal TMS during a number comparison task, while basing TMS localization
      either on (i) individual fMRI-guided TMS neuronavigation, (ii) individual MRI
      guided TMS neuronavigation, (iii) group functional Talairach coordinates, or (iv)
      10-20 EEG position P4. We quantified the exact behavioral effects induced by TMS
      using each approach, calculated the standardized experimental effect sizes, and
      conducted a statistical power analysis in order to calculate the optimal sample
      size required to reveal statistical significance. Our findings revealed a
      systematic difference between the four approaches, with the individual fMRI
      guided TMS neuronavigation yielding the strongest and the P4 stimulation approach
      yielding the smallest behavioral effect size. Accordingly, power analyses
      revealed that although in the fMRI-guided neuronavigation approach five
      participants were sufficient to reveal a significant behavioral effect, the
      number of necessary participants increased to n = 9 when employing MRI-guided
      neuronavigation, to n = 13 in case of TMS based on group Talairach coordinates,
      and to n = 47 when applying TMS over P4. We discuss these graded effect size
      differences in light of the revealed interindividual variances in the actual
      target stimulation site within and between approaches.

PMID- 18823234
TI  - Theta phase synchrony and conscious target perception: impact of intensive mental
      training.
AB  - The information processing capacity of the human mind is limited, as is evidenced
      by the attentional blink-a deficit in identifying the second of two targets (T1
      and T2) presented in close succession. This deficit is thought to result from an
      overinvestment of limited resources in T1 processing. We previously reported that
      intensive mental training in a style of meditation aimed at reducing elaborate
      object processing, reduced brain resource allocation to T1, and improved T2
      accuracy [Slagter, H. A., Lutz, A., Greischar, L. L., Francis, A. D.,
      Nieuwenhuis, S., Davis, J., et al. Mental training affects distribution of
      limited brain resources. PloS Biology, 5, e138, 2007]. Here we report EEG
      spectral analyses to examine the possibility that this reduction in elaborate T1
      processing rendered the system more available to process new target information,
      as indexed by T2-locked phase variability. Intensive mental training was
      associated with decreased cross-trial variability in the phase of oscillatory
      theta activity after successfully detected T2s, in particular, for those
      individuals who showed the greatest reduction in brain resource allocation to T1.
      These data implicate theta phase locking in conscious target perception, and
      suggest that after mental training the cognitive system is more rapidly available
      to process new target information. Mental training was not associated with
      changes in the amplitude of T2-induced responses or oscillatory activity before
      task onset. In combination, these findings illustrate the usefulness of
      systematic mental training in the study of the human mind by revealing the neural
      mechanisms that enable the brain to successfully represent target information.

PMID- 18823236
TI  - Word semantics is processed even without attentional effort.
AB  - We examined the attentional modulation of semantic priming and the N400 effect
      for spoken words. The aim was to find out how the semantics of spoken language is
      processed when attention is directed to another modality (passive task), to the
      phonetics of spoken words (phonological task), or to the semantics of spoken
      words (word task). Equally strong behavioral priming effects were obtained in the
      phonological and the word tasks. A significant N400 effect was found in all
      tasks. The effect was stronger in the word and the phonological tasks than in the
      passive task, but there was no difference in the magnitude of the effect between
      the phonological and the word tasks. The latency of the N400 effect did not
      differ between the tasks. Although the N400 effect had a centroparietal maximum
      in the phonological and the word tasks, it was largest at the parietal recording
      sites in the passive task. The effect was more pronounced at the left than right
      recording sites in the phonological task, but there was no laterality effect in
      the other tasks. The N400 effect in the passive task indicates that semantic
      priming occurs even when spoken words are not actively attended. However,
      stronger N400 effect in the phonological and the word tasks than in the passive
      task suggests that controlled processes modulate the N400 effect. The finding
      that there were no differences in the N400 effect between the phonological and
      the word tasks indicates that the semantics of attended spoken words is processed
      regardless of whether semantic processing is relevant for task performance.

PMID- 18823237
TI  - Learning to become an expert: reinforcement learning and the acquisition of
      perceptual expertise.
AB  - To elucidate the neural mechanisms underlying the development of perceptual
      expertise, we recorded ERPs while participants performed a categorization task.
      We found that as participants learned to discriminate computer generated "blob"
      stimuli, feedback modulated the amplitude of the error-related negativity (ERN)
      an ERP component thought to reflect error evaluation within medial-frontal
      cortex. As participants improved at the categorization task, we also observed an
      increase in amplitude of an ERP component associated with object recognition (the
      N250). The increase in N250 amplitude preceded an increase in amplitude of an ERN
      component associated with internal error evaluation (the response ERN).
      Importantly, these electroencephalographic changes were not observed for
      participants who failed to improve on the categorization task. Our results
      suggest that the acquisition of perceptual expertise relies on interactions
      between the posterior perceptual system and the reinforcement learning system
      involving medial-frontal cortex.

PMID- 18823238
TI  - Decision-making under risk: an fMRI study.
AB  - Recent research has focused on decision-making under risk and its neural bases.
      Two kinds of bad decisions under risk may be defined: too risky decisions and too
      cautious decisions. Here we show that suboptimal decisions of both kinds lead to
      increased activity in the anterior cingulate cortex in a Blackjack gambling task.
      Moreover, this increased activity is related to the avoidance of the negatively
      evaluated decision under risk. These findings complement other results suggesting
      an important role of the dorsal anterior cingulate cortex in reward-based
      decision-making and conflict resolution.

PMID- 18823240
TI  - Conceptual processing in music as revealed by N400 effects on words and musical
      targets.
AB  - The cognitive processing of concepts, that is, abstract general ideas, has been
      mostly studied with language. However, other domains, such as music, can also
      convey concepts. Koelsch et al. [Koelsch, S., Kasper, E., Sammler, D., Schulze,
      K., Gunter, T., & Friederici, A. D. Music, language and meaning: Brain signatures
      of semantic processing. Nature Neuroscience, 7, 302-307, 2004] showed that 10 sec
      of music can influence the semantic processing of words. However, the length of
      the musical excerpts did not allow the authors to study the effect of words on
      musical targets. In this study, we decided to replicate Koelsch et al. findings
      using 1-sec musical excerpts (Experiment 1). This allowed us to study the reverse
      influence, namely, of a linguistic context on conceptual processing of musical
      excerpts (Experiment 2). In both experiments, we recorded behavioral and
      electrophysiological responses while participants were presented 50 related and
      50 unrelated pairs (context/target). Experiments 1 and 2 showed a larger N400
      component of the event-related brain potentials to targets following a
      conceptually unrelated compared to a related context. The presence of an N400
      effect with musical targets suggests that music may convey concepts. The
      relevance of these results for the comprehension of music as a structured set of
      conceptual units and for the domain specificity of the mechanisms underlying N400
      effects are discussed.

PMID- 18823239
TI  - Age-related alterations in simple declarative memory and the effect of negative
      stimulus valence.
AB  - Healthy aging has been shown to modulate the neural circuitry underlying simple
      declarative memory; however, the functional impact of negative stimulus valence
      on these changes has not been fully investigated. Using BOLD fMRI, we explored
      the effects of aging on behavioral performance, neural activity, and functional
      coupling during the encoding and retrieval of novel aversive and neutral scenes.
      Behaviorally, there was a main effect of valence with better recognition
      performance for aversive greater than neutral stimuli in both age groups. There
      was also a main effect of age with better recognition performance in younger
      participants compared to older participants. At the imaging level, there was a
      main effect of valence with increased activity in the medial-temporal lobe
      (amygdala and hippocampus) during both encoding and retrieval of aversive
      relative to neutral stimuli. There was also a main effect of age with older
      participants showing decreased engagement of medial-temporal lobe structures and
      increased engagement of prefrontal structures during both encoding and retrieval
      sessions. Interestingly, older participants presented with relatively decreased
      amygdalar-hippocampal coupling and increased amygdalar-prefrontal coupling when
      compared to younger participants. Furthermore, older participants showed
      increased activation in prefrontal cortices and decreased activation in the
      amygdala when contrasting the retrieval of aversive and neutral scenes. These
      results suggest that although normal aging is associated with a decline in
      declarative memory with alterations in the neural activity and connectivity of
      brain regions underlying simple declarative memory, memory for aversive stimuli
      is relatively better preserved than for neutral stimuli, possibly through greater
      compensatory prefrontal cortical activity.

PMID- 18823241
TI  - Neural evidence of statistical learning: efficient detection of visual
      regularities without awareness.
AB  - Our environment contains regularities distributed in space and time that can be
      detected by way of statistical learning. This unsupervised learning occurs
      without intent or awareness, but little is known about how it relates to other
      types of learning, how it affects perceptual processing, and how quickly it can
      occur. Here we use fMRI during statistical learning to explore these questions.
      Participants viewed statistically structured versus unstructured sequences of
      shapes while performing a task unrelated to the structure. Robust neural
      responses to statistical structure were observed, and these responses were
      notable in four ways: First, responses to structure were observed in the striatum
      and medial temporal lobe, suggesting that statistical learning may be related to
      other forms of associative learning and relational memory. Second, statistical
      regularities yielded greater activation in category-specific visual regions
      (object-selective lateral occipital cortex and word-selective ventral occipito
      temporal cortex), demonstrating that these regions are sensitive to information
      distributed in time. Third, evidence of learning emerged early during
      familiarization, showing that statistical learning can operate very quickly and
      with little exposure. Finally, neural signatures of learning were dissociable
      from subsequent explicit familiarity, suggesting that learning can occur in the
      absence of awareness. Overall, our findings help elucidate the underlying nature
      of statistical learning.

PMID- 18823242
TI  - Recognizing threat: a simple geometric shape activates neural circuitry for
      threat detection.
AB  - The urgent need to recognize danger quickly has been shown to rely on
      preferential processing in dedicated neural circuitry. In previous behavioral
      studies examining the pattern of the face when displaying anger, we found
      evidence that simple noncontextual geometric shapes containing downward-pointing
      V-shaped angles activate the perception of threat. We here report that the neural
      circuitry known to be mobilized by many realistic, contextual threatening
      displays is also triggered by the simplest form of this V-shaped movement
      pattern, a downward-pointing triangle. Specifically, we show that simple
      geometric forms containing only downward-pointing V-shapes elicit greater
      activation of the amygdala, subgenual anterior cingulate cortex, superior
      temporal gyrus, and fusiform gyrus, as well as extrastriate visual regions, than
      do presentations of the identical V-shape pointing upward. Thus, this simple V
      shape is capable of activating neural networks instantiating detection of threat
      and negative affect, suggesting that recognition of potential danger may be
      based, in part, on very simple, context-free visual cues.

PMID- 18823243
TI  - Seeing sounds and hearing colors: an event-related potential study of auditory
      visual synesthesia.
AB  - In auditory-visual synesthesia, sounds automatically elicit conscious and
      reliable visual experiences. It is presently unknown whether this reflects early
      or late processes in the brain. It is also unknown whether adult audiovisual
      synesthesia resembles auditory-induced visual illusions that can sometimes occur
      in the general population or whether it resembles the electrophysiological
      deflection over occipital sites that has been noted in infancy and has been
      likened to synesthesia. Electrical brain activity was recorded from adult
      synesthetes and control participants who were played brief tones and required to
      monitor for an infrequent auditory target. The synesthetes were instructed to
      attend either to the auditory or to the visual (i.e., synesthetic) dimension of
      the tone, whereas the controls attended to the auditory dimension alone. There
      were clear differences between synesthetes and controls that emerged early (100
      msec after tone onset). These differences tended to lie in deflections of the
      auditory-evoked potential (e.g., the auditory N1, P2, and N2) rather than the
      presence of an additional posterior deflection. The differences occurred
      irrespective of what the synesthetes attended to (although attention had a late
      effect). The results suggest that differences between synesthetes and others
      occur early in time, and that synesthesia is qualitatively different from similar
      effects found in infants and certain auditory-induced visual illusions in adults.
      In addition, we report two novel cases of synesthesia in which colors elicit
      sounds, and vice versa.

PMID- 18823244
TI  - ERP evidence for flexible adjustment of retrieval orientation and its influence
      on familiarity.
AB  - The assumption was tested that familiarity memory as indexed by a mid-frontal ERP
      old-new effect is modulated by retrieval orientation. A randomly cued category
      based versus exemplar-specific recognition memory test, requiring flexible
      adjustment of retrieval orientation, was conducted. Results show that the mid
      frontal ERP old-new effect is sensitive to the manipulation of study-test
      congruency-that is, whether the same object is repeated identically or a
      different category exemplar is presented at test. Importantly, the effect pattern
      depends on subjects' retrieval orientation. With a specific orientation, only
      same items elicited an early old-new effect (same > different = new), whereas in
      the general condition, the old-new effect was graded (same > different > new).
      This supports the view that both perceptual and conceptual processes can
      contribute to familiarity memory and demonstrates that the rather automatic
      process of familiarity is not only data driven but influenced by top-down
      retrieval orientation, which subjects are able to adjust on a flexible basis.

PMID- 18823245
TI  - Neural priming in human frontal cortex: multiple forms of learning reduce demands
      on the prefrontal executive system.
AB  - Past experience is hypothesized to reduce computational demands in PFC by
      providing bottom-up predictive information that informs subsequent stimulus
      action mapping. The present fMRI study measured cortical activity reductions
      ("neural priming"/"repetition suppression") during repeated stimulus
      classification to investigate the mechanisms through which learning from the past
      decreases demands on the prefrontal executive system. Manipulation of learning at
      three levels of representation-stimulus, decision, and response-revealed
      dissociable neural priming effects in distinct frontotemporal regions, supporting
      a multiprocess model of neural priming. Critically, three distinct patterns of
      neural priming were identified in lateral frontal cortex, indicating that frontal
      computational demands are reduced by three forms of learning: (a) cortical tuning
      of stimulus-specific representations, (b) retrieval of learned stimulus-decision
      mappings, and (c) retrieval of learned stimulus-response mappings. The
      topographic distribution of these neural priming effects suggests a rostrocaudal
      organization of executive function in lateral frontal cortex.

PMID- 18823246
TI  - Distinct hippocampal and basal ganglia contributions to probabilistic learning
      and reversal.
AB  - The hippocampus and the basal ganglia are thought to play fundamental and
      distinct roles in learning and memory, supporting two dissociable memory systems.
      Interestingly, however, the hippocampus and the basal ganglia have each,
      separately, been implicated as necessary for reversal learning-the ability to
      adaptively change a response when previously learned stimulus-outcome
      contingencies are reversed. Here, we compared the contribution of the hippocampus
      and the basal ganglia to distinct aspects of learning and reversal. Amnesic
      subjects with selective hippocampal damage, Parkinson subjects with disrupted
      basal ganglia function, and healthy controls were tested on a novel probabilistic
      learning and reversal paradigm. In this task, reversal can be achieved in two
      ways: Subjects can reverse a previously learned response, or they can select a
      new cue during the reversal phase, effectively "opting out" of the reversal. We
      found that both patient groups were intact at initial learning, but differed in
      their ability to reverse. Amnesic subjects failed to reverse, and continued to
      use the same cue and response learned before the reversal. Parkinson subjects, by
      contrast, opted out of the reversal by learning a new cue-outcome association.
      These results suggest that both the hippocampus and the basal ganglia support
      reversal learning, but in different ways. The basal ganglia are necessary for
      learning a new response when a previously learned response is no longer
      rewarding. The failure of the amnesic subjects to reverse their response or to
      learn a new cue is consistent with a more general role for the hippocampus in
      configural learning, and suggests it may also support the ability to respond to
      changes in cue-outcome contingencies.

PMID- 18823247
TI  - Target selection by the frontal cortex during coordinated saccadic and smooth
      pursuit eye movements.
AB  - Oculomotor tracking of moving objects is an important component of visually based
      cognition and planning. Such tracking is achieved by a combination of saccades
      and smooth-pursuit eye movements. In particular, the saccadic and smooth-pursuit
      systems interact to often choose the same target, and to maximize its visibility
      through time. How do multiple brain regions interact, including frontal cortical
      areas, to decide the choice of a target among several competing moving stimuli?
      How is target selection information that is created by a bias (e.g., electrical
      stimulation) transferred from one movement system to another? These saccade
      pursuit interactions are clarified by a new computational neural model, which
      describes interactions between motion processing areas: the middle temporal area,
      the middle superior temporal area, the frontal pursuit area, and the dorsal
      lateral pontine nucleus; saccade specification, selection, and planning areas:
      the lateral intraparietal area, the frontal eye fields, the substantia nigra pars
      reticulata, and the superior colliculus; the saccadic generator in the brain
      stem; and the cerebellum. Model simulations explain a broad range of
      neuroanatomical and neurophysiological data. These results are in contrast with
      the simplest parallel model with no interactions between saccades and pursuit
      other than common-target selection and recruitment of shared motoneurons. Actual
      tracking episodes in primates reveal multiple systematic deviations from
      predictions of the simplest parallel model, which are explained by the current
      model.

PMID- 18823248
TI  - Anticipating conflict facilitates controlled stimulus-response selection.
AB  - Cognitive control can be triggered in reaction to previous conflict, as suggested
      by the finding of sequential effects in conflict tasks. Can control also be
      triggered proactively by presenting cues predicting conflict ("proactive
      control")? We exploited the high temporal resolution of ERPs and controlled for
      sequential effects to ask whether proactive control based on anticipating
      conflict modulates neural activity related to cognitive control, as may be
      predicted from the conflict-monitoring model. ERPs associated with conflict
      detection (N2) were measured during a cued flanker task. Symbolic cues were
      either informative or neutral with respect to whether the target involved
      conflicting or congruent responses. Sequential effects were controlled by
      analyzing the congruency of the previous trial. The results showed that cueing
      conflict facilitated conflict resolution and reduced the N2 latency. Other
      potentials (frontal N1 and P3) were also modulated by cueing conflict. Cueing
      effects were most evident after congruent than after incongruent trials. This
      interaction between cueing and sequential effects suggests neural overlap between
      the control networks triggered by proactive and reactive signals. This finding
      clarifies why previous neuroimaging studies, in which reactive sequential effects
      were not controlled, have rarely found anticipatory effects upon conflict-related
      activity. Finally, the high temporal resolution of ERPs was critical to reveal a
      temporal modulation of conflict detection by proactive control. This novel
      finding suggests that anticipating conflict speeds up conflict detection and
      resolution. Recent research suggests that this anticipatory mechanism may be
      mediated by preactivation of ACC during the preparatory interval.

PMID- 18823249
TI  - A multisensory cortical network for understanding speech in noise.
AB  - In noisy environments, listeners tend to hear a speaker's voice yet struggle to
      understand what is said. The most effective way to improve intelligibility in
      such conditions is to watch the speaker's mouth movements. Here we identify the
      neural networks that distinguish understanding from merely hearing speech, and
      determine how the brain applies visual information to improve intelligibility.
      Using functional magnetic resonance imaging, we show that understanding speech-in
      noise is supported by a network of brain areas including the left superior
      parietal lobule, the motor/premotor cortex, and the left anterior superior
      temporal sulcus (STS), a likely apex of the acoustic processing hierarchy.
      Multisensory integration likely improves comprehension through improved
      communication between the left temporal-occipital boundary, the left medial
      temporal lobe, and the left STS. This demonstrates how the brain uses information
      from multiple modalities to improve speech comprehension in naturalistic,
      acoustically adverse conditions.

PMID- 18823250
TI  - An FMRI investigation of spontaneous mental state inference for moral judgment.
AB  - Human moral judgment depends critically on "theory of mind," the capacity to
      represent the mental states of agents. Recent studies suggest that the right TPJ
      (RTPJ) and, to lesser extent, the left TPJ (LTPJ), the precuneus (PC), and the
      medial pFC (MPFC) are robustly recruited when participants read explicit
      statements of an agent's beliefs and then judge the moral status of the agent's
      action. Real-world interactions, by contrast, often require social partners to
      infer each other's mental states. The current study uses fMRI to probe the role
      of these brain regions in supporting spontaneous mental state inference in the
      service of moral judgment. Participants read descriptions of a protagonist's
      action and then either (i) "moral" facts about the action's effect on another
      person or (ii) "nonmoral" facts about the situation. The RTPJ, PC, and MPFC were
      recruited selectively for moral over nonmoral facts, suggesting that processing
      moral stimuli elicits spontaneous mental state inference. In a second experiment,
      participants read the same scenarios, but explicit statements of belief preceded
      the facts: Protagonists believed their actions would cause harm or not. The
      response in the RTPJ, PC, and LTPJ was again higher for moral facts but also
      distinguished between neutral and negative outcomes. Together, the results
      illuminate two aspects of theory of mind in moral judgment: (1) spontaneous
      belief inference and (2) stimulus-driven belief integration.

PMID- 18823251
TI  - Neural correlates of stimulus reportability.
AB  - Most experiments on the "neural correlates of consciousness" employ stimulus
      reportability as an operational definition of what is consciously perceived. The
      interpretation of such experiments therefore depends critically on understanding
      the neural basis of stimulus reportability. Using a high volume of fMRI data, we
      investigated the neural correlates of stimulus reportability using a partial
      report object detection paradigm. Subjects were presented with a random array of
      circularly arranged disc-stimuli and were cued, after variable delays (following
      stimulus offset), to report the presence or absence of a disc at the cued
      location, using variable motor actions. By uncoupling stimulus processing,
      decision, and motor response, we were able to use signal detection theory to
      deconstruct the neural basis of stimulus reportability. We show that
      retinotopically specific responses in the early visual cortex correlate with
      stimulus processing but not decision or report; a network of parietal/temporal
      regions correlates with decisions but not stimulus presence, whereas classical
      motor regions correlate with report. These findings provide a basic framework for
      understanding the neural basis of stimulus reportability without the theoretical
      burden of presupposing a relationship between reportability and consciousness.

PMID- 18823252
TI  - Attending to multiple visual streams: interactions between location-based and
      category-based attentional selection.
AB  - Behavioral studies indicate that subjects are able to divide attention between
      multiple streams of information at different locations. However, it is still
      unclear to what extent the observed costs reflect processes specifically
      associated with spatial attention, versus more general interference due the
      concurrent monitoring of multiple streams of stimuli. Here we used a factorial
      design to disentangle the correlates of location- versus category-based selection
      processes during fMRI. In all conditions, participants were presented with two
      overlapping visual stimuli (red shapes and green shapes) in each hemifield. In
      different blocks, subjects either: (1) attended to one single stimulus category,
      red shapes or green shapes, in one hemifield; (2) attended to both stimulus
      categories in the same hemifield; (3) attended to one single stimulus category,
      but monitoring both hemifields at the same time; or (4) attended to one stimulus
      category in one hemifield, and the other category in the opposite hemifield. The
      behavioral data showed the expected costs of dividing spatial attention across
      the two hemifields, and the cost of monitoring two stimulus categories versus one
      category. The imaging data revealed activation of a dorsal fronto-parietal
      network, both for dividing spatial attention and for monitoring multiple stimulus
      categories. However, unlike behavioral data, the imaging results also showed a
      significant interaction between location- and category-based attention within the
      same network. This demonstrates that the fronto-parietal cortex engages in both
      of these selective attention functions, and that a mere increase in task
      difficulty cannot explain colocalization of these processes. We conclude that,
      under conditions of multiple streams monitoring, fronto-parietal regions control
      location- and category-based attentional selection.

PMID- 18823253
TI  - Time course of evoked-potential changes in different forms of anomia in aphasia.
AB  - Impaired word production after brain damage can be due to impairment at lexical
      semantic or at lexical-phonological levels of word encoding. These processes are
      thought to involve different brain regions and to have different time courses.
      The present study investigated the time course of electrophysiological correlates
      of anomia in 16 aphasic speakers, divided in two subgroups according to their
      anomic pattern (8 with lexical-semantic impairment and 8 with lexical
      phonological impairment), in comparison to 16 healthy control subjects performing
      the same picture naming task. Differences in amplitudes and in topographic maps
      between groups were differently distributed when the whole heterogeneous group of
      aphasic patients was compared to the control group and when the two more
      homogeneous subgroups of anomic patients were analyzed. The entire aphasic group
      expressed different waveforms and topographic patterns than the control group
      starting about 100 msec after picture presentation. When two subgroups of aphasic
      patients are considered according to the underlying cognitive impairment, early
      event-related potential (ERP) abnormalities (100-250 msec) appeared only in the
      lexical-semantic subgroup, whereas later ERP abnormalities (300-450 msec)
      occurred only in the lexical-phonological subgroup. These results indicate that
      the time windows of ERP abnormalities vary depending on the underlying anomic
      impairment. Moreover, the findings give support to current hypotheses on the time
      course of processes involved in word production during picture naming.

PMID- 18823254
TI  - Semantic context and visual feature effects in object naming: an fMRI study using
      arterial spin labeling.
AB  - Previous behavioral studies reported a robust effect of increased naming
      latencies when objects to be named were blocked within semantic category,
      compared to items blocked between category. This semantic context effect has been
      attributed to various mechanisms including inhibition or excitation of lexico
      semantic representations and incremental learning of associations between
      semantic features and names, and is hypothesized to increase demands on verbal
      self-monitoring during speech production. Objects within categories also share
      many visual structural features, introducing a potential confound when
      interpreting the level at which the context effect might occur. Consistent with
      previous findings, we report a significant increase in response latencies when
      naming categorically related objects within blocks, an effect associated with
      increased perfusion fMRI signal bilaterally in the hippocampus and in the left
      middle to posterior superior temporal cortex. No perfusion changes were observed
      in the middle section of the left middle temporal cortex, a region associated
      with retrieval of lexical-semantic information in previous object naming studies.
      Although a manipulation of visual feature similarity did not influence naming
      latencies, we observed perfusion increases in the perirhinal cortex for naming
      objects with similar visual features that interacted with the semantic context in
      which objects were named. These results provide support for the view that the
      semantic context effect in object naming occurs due to an incremental learning
      mechanism, and involves increased demands on verbal self-monitoring.

PMID- 18823255
TI  - Functional specialization and convergence in the occipito-temporal cortex
      supporting haptic and visual identification of human faces and body parts: an
      fMRI study.
AB  - Humans can recognize common objects by touch extremely well whenever vision is
      unavailable. Despite its importance to a thorough understanding of human object
      recognition, the neuroscientific study of this topic has been relatively
      neglected. To date, the few published studies have addressed the haptic
      recognition of nonbiological objects. We now focus on haptic recognition of the
      human body, a particularly salient object category for touch. Neuroimaging
      studies demonstrate that regions of the occipito-temporal cortex are specialized
      for visual perception of faces (fusiform face area, FFA) and other body parts
      (extrastriate body area, EBA). Are the same category-sensitive regions activated
      when these components of the body are recognized haptically? Here, we use fMRI to
      compare brain organization for haptic and visual recognition of human body parts.
      Sixteen subjects identified exemplars of faces, hands, feet, and nonbiological
      control objects using vision and haptics separately. We identified two discrete
      regions within the fusiform gyrus (FFA and the haptic face region) that were each
      sensitive to both haptically and visually presented faces; however, these two
      regions differed significantly in their response patterns. Similarly, two regions
      within the lateral occipito-temporal area (EBA and the haptic body region) were
      each sensitive to body parts in both modalities, although the response patterns
      differed. Thus, although the fusiform gyrus and the lateral occipito-temporal
      cortex appear to exhibit modality-independent, category-sensitive activity, our
      results also indicate a degree of functional specialization related to sensory
      modality within these structures.

PMID- 18823256
TI  - Increased expression of glutathione peroxidase 4 strongly protects retina from
      oxidative damage.
AB  - Oxidative damage contributes to cone cell death in retinitis pigmentosa and death
      of rods, cones, and retinal pigmented epithelial (RPE) cells in age-related
      macular degeneration. In this study, we explored the strategy of overexpressing
      components of the endogenous antioxidant defense system to combat oxidative
      damage in RPE cells and retina. In transfected cultured RPE cells with increased
      expression of superoxide dismutase1 (SOD1) or SOD2, there was increased
      constitutive and stress-induced oxidative damage measured by the level of
      carbonyl adducts on proteins. In contrast, RPE cells with increased expression of
      glutathione peroxidase 1 (Gpx1) or Gpx4 did not show an increase in constitutive
      oxidative damage. An increase in Gpx4, and to a lesser extent Gpx1, reduced
      oxidative stress-induced RPE cell damage. Co-expression of Gpx4 with SOD1 or 2
      partially reversed the deleterious effects of the SODs. Transgenic mice with
      inducible expression of Gpx4 in photoreceptors were generated, and in three
      models of oxidative damage-induced retinal degeneration, increased expression of
      Gpx4 provided strong protection of retinal structure and function. These data
      suggest that gene therapy approaches to augment the activity of Gpx4 in the
      retina and RPE should be considered in patients with retinitis pigmentosa or age
      related macular degeneration.

PMID- 18823257
TI  - Handling of and preferences for available dry powder inhaler systems by patients
      with asthma and COPD.
AB  - The correct handling of dry powder inhalers (DPIs) is crucial for efficient
      therapy, and acceptance of the device can improve compliance. The handling of
      seven different dry powder inhalers was studied in 72 patients with asthma and
      chronic obstructive pulmonary disease (COPD). The aim of this study was to
      identify possible handling errors and investigate patient preferences. Patients
      inhaled twice with each inhaler; first after reading the device leaflet, and
      second after device handling was explained by the investigator. The investigator
      identified handling errors and critical handling errors, which might lead to
      insufficient or no dose delivery. Afterward, the patients selected their
      preferred device and judged different aspects of device handling. The lowest
      number of patients with critical handling errors was observed for the
      Diskus/Accuhaler, the highest numbers for the Jethaler and the Easyhaler (% of
      patients during first/second use): Diskus/Accuhaler 25%/13.9% (group A) and
      38.9%/8.3% (group B); Clickhaler 50.0%/52.8%, Cyclohaler 58.3%/13.9%, Jethaler
      66.7%/30.6% (group A) and Benosid N Inhaler 52.8%/22.2%, Novolizer 52.8%/25.0%,
      Easyhaler 72.2%/47.2% (group B). Device handling improved after instruction by
      the investigator. Device handling and preferences of patients closely correlated
      in this study. Both devices producing the lowest numbers of handling errors
      (Diskus/Accuhaler and Clickhaler) had the highest preference by the subjects
      (score from 1 = very good to 7 = very bad): Diskus/Accuhaler 2.21 (group A) and
      2.02 (group B); Clickhaler 2.21, Cyclohaler 2.80, Jethaler 3.16 (group A);
      Novolizer 2.33, Easyhaler 2.37, Benosid N Inhaler 2.43 (group B). Critical
      handling errors may reduce therapy outcome due to a reduced dose delivery. In
      addition, reduced patients acceptance of a device, being dependent on device
      handling, may have a similar effect by reducing patients' compliance.

PMID- 18823258
TI  - Phospholipid-induced in vivo particle migration to enhance pulmonary deposition.
AB  - Amount of drug actually reaching the target region in the lung following
      pulmonary inhalation is often estimated at less than 10% for older devices.
      Current particle and device engineering technologies have improved on this but
      still fail to recover the "wasted" fraction of the drug and deliver it deeper
      into the lungs, which is generally desirable. FDA has approved several exogenous
      surfactants for prophylaxis and rescue treatment of respiratory distress syndrome
      (RDS). Their approved mode of administration (intratracheal instillation) and
      site of action (alveolar spaces) suggest that the phospholipids in the exogenous
      surfactants can spread from the trachea to alveolar air spaces and exert
      advantageous effects. We investigated whether in vivo lung migration of particles
      based on this phenomenon was possible and could be quantified based on changes in
      total and regional deposition of fluorescently labeled latex beads, utilized as
      an insoluble drug model. Following intranasal administration of beads, migration
      to rodent lungs was monitored upon intranasal instillation of Survanta (exogenous
      surfactant) or saline (control). After intranasal instillation approximately 12%
      of beads were found to migrate to the lung, and total lung deposition increased
      by approximately 10% on administration of Survanta or saline (control). After
      intranasal administration approximately 1% of beads in the lung were found to
      migrate to peripheral regions of the lungs, and a four- to six-fold increase in
      peripheral lung deposition was observed after Survanta instillation, compared to
      the saline control, which was determined to be independent of dose and volume of
      Survanta instillate in the range we studied. The in vivo rodent studies provided
      support for the idea that intranasally administered particles deposited in non
      target lung locations may be translocated to peripheral sites in the lung
      therapeutically after surfactant application.

PMID- 18823259
TI  - Deposition-dependent normal ranges for radioaerosol assessment of lung mucus
      clearance.
AB  - Deposition distribution variability strongly influences data from radioaerosol
      mucus clearance measurements. We investigated how one clearance measurement-the
      area under the 0-6 h tracheobronchial retention curve (AUC)-relates to three
      different indices characterizing initial particle distribution. These indices
      were a conventional penetration index (PI), retention at 24 h (R(24)) and an
      Airways Penetration Index (API). API is an estimate of an outer to inner zone
      ratio for "tracheobronchial" (short-term cleared) deposition. Data were analyzed
      from "control" tests on 35 normal nonsmoking volunteers (16 females, 19 males,
      age 18-72 years). The strongest clearance-deposition correlation (r = 0.84, p <
      0.0001) was obtained with API, yielding a narrower normal range than those with
      PI or R(24). No influence of age was detected. Data from repeat tests on 17
      subjects demonstrated AUC changes correlating closely with API changes (r = 0.92,
      p < 0.0001), confirming the potential value of API as a "predictor" of clearance
      changes resulting simply from a changed distribution of initial deposition along
      the tracheobronchial airway generations. Additional data from 19 "placebo" tests
      on normal subjects gave AUC values within or close to suggested normal confidence
      limits derived from the control subject plots of AUC against, respectively, PI,
      R(24), and API. Quantitative attention to the influence of depositionclearance
      relationships should help in analyzing data from studies where posttreatment
      aerosol distribution cannot be exactly matched to the pretreatment situation.
      Deposition-corrected clearance provides an approach to improved estimation of
      clearance "normality."

PMID- 18823260
TI  - Sustained mechanical and clinical functionality of the flexhaler dry powder
      inhaler.
AB  - Flexhaler is a multiple-dose, inspiratory flow-driven dry powder inhaler that is
      a newer version of Turbuhaler, and is identical to the Symbicort Turbuhaler.
      Sustained performance is of the utmost importance to ensure consistent drug
      delivery throughout the lifespan of the inhaler. We report functionality testing
      results of Flexhaler inhalers used in two large-scale 12-week studies of
      budesonide (Pulmicort) and returned for testing. Functionality tests included
      measurement of airflow resistance and inspection of vital parts for the
      mechanical functionality of the inhaler, including visual inspection of the
      indicator wheel and function check of dose loading. In addition, delivered dose,
      particle size distribution, moisture content, and microbial counts were
      evaluated. Seven hundred sixteen out of 720 units were returned. Airflow
      resistance was not affected by the handling of the Flexhaler inhalers during use
      (prior to use, average airflow resistance: 67 Pa(0.5)*s*L(-1); returned inhalers:
      66 and 67 Pa(0.5)*s*L(-1) in each study, respectively. The average dose delivered
      remained as intended after prolonged clinical use [95% (range 88 -103%) vs.
      reference of 99% (range 93-104%) before issue]. Relative fine particle dose ( <5
      mum) after use was 107% (range 96-111%) of the reference value before issue.
      Moisture content in the inhaler desiccant was 3-25%, suggesting variability in
      storage conditions. Among the 28 inhalers randomly selected for microbiological
      testing there was no or very limited microbial growth. All 14 inhalers returned
      with functionality issues operated as intended and no reported functionality
      issues could be confirmed. Flexhaler inhalers operated as intended during these
      two clinical trials. These results should reassure both clinicians and patients
      with respect to the consistent quality of this unit for the delivery of dry
      powder formulations for inhalation.

PMID- 18823261
TI  - Qigong stress reduction in hospital staff.
AB  - OBJECTIVE: The aim of this study was to investigate the effectiveness of a qigong
      training program in reducing stress in hospital staff. METHODS: Subjects were
      randomly assigned to a 6-week intervention of either qigong practice (n = 16) or
      a waiting list (n = 21). The primary measure of stress was the Perceived Stress
      Scale. Secondary measures included the Short Form 36 (SF-36) quality-of-life
      measure and a 100-mm analog pain scale. RESULTS: The qigong group demonstrated a
      statistically significant reduction of perceived stress compared to the control
      group (p = 0.02). On the Social Interaction subscale of the SF-36, the qigong
      group demonstrated greater improvement compared to controls (p = 0.04). Within
      groups analyses demonstrated that the qigong group (p = 0.03), but not the
      control group, experienced a significant reduction of pain intensity. A
      regression analysis demonstrated an association between higher baseline stress
      levels and greater improvement within the qigong group (R(2) = 0.34; p = 0.02).
      CONCLUSIONS: These results suggest that short-term exposure to qigong was
      effective in reducing stress in hospital staff. Further studies are needed to
      evaluate the possible effectiveness of qigong in reducing pain and in improving
      quality of life.

PMID- 18823262
TI  - Qigong: bio-energy medicine.

PMID- 18823263
TI  - Potential use of a monoclonal antibody for the detection of Candida antigens in
      an experimental systemic candidiasis model.
AB  - The Candida species are the most common fungal pathogens of systemic candidiasis.
      The diagnosis of invasive candidiasis remains a laboratory and clinical
      challenge. Thus, development of diagnostic assays to detect systemic candidiasis
      and to identify Candida virulence factors and associated pathogenesis through
      immunohistochemistry using specific monoclonals and polyclonals will be useful.
      Inbred Balb/c mice were immunized with C. albicans antigens, and blood was
      checked for the presence of reactive antibodies using ELISA. Fusion was performed
      using the harvested spleen cells and NS1 myeloma cells, and the clones were
      screened for the presence of antibody producing hybrid cells by dot-blot. Western
      blot analysis showed that the L2D10 monoclonal antibody was reactive against the
      antigens with molecular weight of 20 kDa. Experimental systemic candidiasis in
      mice was induced through intravenous injection of C. albicans and all the vital
      organs were collected for immunohistochemistry study. The monoclonal antibody
      reacted to surface epitopes on the yeast cells, germ tubes, and hyphae, and to
      immune complexes. It was used with the polyclonal antibody in a sandwich ELISA
      for the detection of circulating antigens in experimental candiadiasis in mice.
      Antibody levels were also determined using the ELISA method, and the antibody
      levels of C. albicans infected mice were increased compared with uninfected
      animals. The monoclonal antibody was used in immunoperoxidase and
      immunofluorescence techniques for the detection of fungal infection in tissue
      sections and was found to be more sensitive than conventional periodic acid
      Schiff or silver staining techniques. This monoclonal antibody may serve as
      potential primary capture antibodies for the development of a rapid diagnostic
      test for human systemic fungal infection.

PMID- 18823264
TI  - Cells derived from human umbilical cord blood support the long-term growth of
      undifferentiated human embryonic stem cells.
AB  - Various types of human cells have been tested as feeder cells for the
      undifferentiated growth of human embryonic stem cells (hESCs) in vitro. We report
      here the successful culture of two hESC lines (H1 and H9) on human umbilical cord
      blood (UCB)-derived fibroblast-like cells. These cells permit the long-term
      continuous growth of undifferentiated and pluripotent hESCs. The cultured hESCs
      had normal karyotypes, expressed OCT-4, SSEA-4, TRA-1-60, and TRA-1-81, formed
      cystic embryonic body in vitro and teratomas in vivo after injected into
      immunodeficient mice. The wide availability of clinical-grade human UCB makes it
      a promising source of support cells for the growth of hESC for use in cell
      therapies.

PMID- 18823265
TI  - Transgene expression of green fluorescent protein and germ line transmission in
      cloned pigs derived from in vitro transfected adult fibroblasts.
AB  - The pig represents the xenogeneic donor of choice for future organ
      transplantation in humans for anatomical and physiological reasons. However, to
      bypass several immunological barriers, strong and stable human genes expression
      must occur in the pig's organs. In this study we created transgenic pigs using in
      vitro transfection of cultured cells combined with somatic cell nuclear transfer
      (SCNT) to evaluate the ubiquitous transgene expression driven by pCAGGS vector in
      presence of different selectors. pCAGGS confirmed to be a very effective vector
      for ubiquitous transgene expression, irrespective of the selector that was used.
      Green fluorescent protein (GFP) expression observed in transfected fibroblasts
      was also maintained after nuclear transfer, through pre- and postimplantation
      development, at birth and during adulthood. Germ line transmission without
      silencing of the transgene was demonstrated. The ubiquitous expression of GFP was
      clearly confirmed in several tissues including endothelial cells, thus making it
      a suitable vector for the expression of multiple genes relevant to
      xenotransplantation where tissue specificity is not required. Finally
      cotransfection of green and red fluorescence protein transgenes was performed in
      fibroblasts and after nuclear transfer blastocysts expressing both fluorescent
      proteins were obtained.

PMID- 18823266
TI  - BMP4 induces primitive endoderm but not trophectoderm in monkey embryonic stem
      cells.
AB  - Monkey embryonic stem (ES) cells share similar characteristics to human ES cells
      and provide a primate model of allotransplantation, which allows to validate
      efficacy and safety of cell transplantation therapy in regenerative medicine.
      Bone morphogenetic protein 4 (BMP4) is known to promote trophoblast
      differentiation in human ES cells in contrast to mouse ES cells where BMP4
      synergistically maintains self-renewal with leukemia inhibitory factor (LIF),
      which represents a significant difference in signal transduction of self-renewal
      and differentiation between murine and human ES cells. As the similarity of the
      differentiation mechanism between monkey and human ES cells is of critical
      importance for their use as a primate model system, we investigated whether BMP4
      induces trophoblast differentiation in monkey ES cells. Interestingly, BMP4 did
      not induce trophoblast differentiation, but instead induced primitive endoderm
      differentiation. Prominent downregulation of Sox2, which plays a pivotal role not
      only in pluripotency but also placenta development, was observed in cells treated
      with BMP4. In addition, upregulation of Hand1, Cdx2, and chorionic gonadotropin
      beta (CG-beta), which are markers of trophoblast, was not observed. In contrast,
      BMP4 induced significant upregulation of Gata6, Gata4, and LamininB1, suggesting
      differentiation into the primitive endoderm, visceral endoderm, and parietal
      endoderm, respectively. The threshold of BMP4 activity was estimated as about 10
      ng/mL. These findings suggest that BMP4 induced differentiation into the
      primitive endoderm lineage but not into trophoblast in monkey ES cells.

PMID- 18823267
TI  - Clarification of the Agreement between the Infectious Diseases Society of America
      and the Attorney General of Connecticut.

PMID- 18823268
TI  - Tuberculosis transmission by patients with smear-negative pulmonary tuberculosis
      in a large cohort in the Netherlands.
AB  - BACKGROUND: Sputum smear microscopy is commonly used for diagnosing tuberculosis
      (TB). Although patients with sputum smear-negative TB are less infectious than
      patients with smear-positive TB, they also contribute to TB transmission. The
      objective of this study was to determine the proportion of TB transmission events
      caused by patients with smear-negative pulmonary TB in The Netherlands. METHODS:
      All patients in The Netherlands with culture-confirmed TB during the period 1996
      2004 were included in this study. Patients with identical DNA fingerprints in
      Mycobacterium tuberculosis isolates from sputum samples were clustered. The first
      patients in a cluster were considered to be the index patients; all other
      patients were considered to have secondary cases. In addition, we examined
      transmission from sources by conventional contact tracing. RESULTS: We analyzed
      394 clusters with a total of 1285 patients. On the basis of molecular linkage
      only, 12.6% of the secondary cases were attributable to transmission from a
      patient with smear-negative TB. The relative transmission rate among patients
      with smear-negative TB, compared with patients with smear-positive TB, was 0.24
      (95% confidence interval, 0.20-0.30). Secondary cases in clusters with an index
      patient with smear-negative TB more frequently had smear-negative status (odds
      ratio, 1.86; 95% confidence interval, 1.18-2.93), compared with secondary cases
      in clusters with an index patient with smear-positive TB. Conventional contact
      tracing revealed that 26 (6.2%) of the 417 sources, as identified by the
      Municipal Health Services, had smear-negative TB. CONCLUSIONS: In The
      Netherlands, patients with smear-negative, culture-positive TB are responsible
      for 13% of TB transmission. Countries that have ample resources should expand
      their TB-control efforts to include prevention of transmission from patients with
      smear-negative, culture-positive pulmonary TB.

PMID- 18823269
TI  - Large outbreak of measles in a community with high vaccination coverage:
      implications for the vaccination schedule.
AB  - BACKGROUND: Attempts to eliminate measles from a country or region may be
      disrupted by an imported case that affects indigenous persons. The objective of
      this study was to analyze epidemiological and clinical characteristics of a
      measles outbreak in Catalonia, Spain, in 2006. METHODS: Data on cases of measles
      reported to the Department of Health, Generalitat of Catalonia, during the period
      28 August 2006 through 8 July 2007 were collected. Suspected cases were confirmed
      by determination of measles-specific immunoglobulin M antibodies and/or detection
      of virus genome. Incidences were calculated using the estimated population of
      Catalonia for 2006, and 95% confidence intervals were determined assuming a
      Poisson distribution. The association between proportions was determined using
      the chi(2) test and Fisher's exact test. The level of statistical significance
      was set at alpha = .05. RESULTS: A total of 381 cases were confirmed, for an
      incidence of 6.6 cases per 100,000 persons. A total of 89.5% of cases occurred in
      nonvaccinated persons, mainly those aged < or =15 months (incidence, 278.2 cases
      per 100,000 persons; mean age of patients, 12 months). Indigenous subjects
      accounted for 89.8% of cases, and laboratory confirmation of results was obtained
      for 87.1%. Measles genotype D4 was identified in all sequenced samples.
      CONCLUSIONS: The age distribution of cases of measles among children aged <15
      months suggests that the first dose of vaccine should be routinely administered
      at the age of 12 months.

PMID- 18823270
TI  - Exploration of the effectiveness of social distancing on respiratory pathogen
      transmission implicates environmental contributions.
AB  - BACKGROUND: In both military and civilian settings, transmission of respiratory
      pathogens may be due to person-to-person and environmental contributions. This
      possibility was explored in a military training setting, where rates of febrile
      respiratory illness (FRI) often reach epidemic levels. METHODS: Population size
      and FRI rates were monitored over 10 months in the units of 50-90 individuals.
      Some units were open to the influx of potentially infectious convalescents
      (hereafter referred to as "open units," and some were closed to such an influx
      (hereafter referred to as "closed units"). Virologic testing and polymerase chain
      reaction analysis were used to detect adenovirus on surface structures. RESULTS:
      The odds ratio (OR) associated with FRI in closed units, compared with open
      units, was 1.13 (95% confidence interval [CI], 0.99-1.28). The OR in units with a
      population greater than the median size, compared with units with a population
      lower than the median size was 1.38 (95% CI, 1.23-1.55). Between 5% and 9% of
      surface samples obtained from selected units harbored viable adenovirus.
      CONCLUSIONS: FRI rates were not reduced in units that were closed to potentially
      contagious individuals. These findings imply that the primary source of the
      pathogen is likely environmental rather than human, and they underscore what is
      known about other virus types. Diligence in identifying the relative roles of
      different transmission routes is suggested for civilian settings similar to those
      described in the current study.

PMID- 18823271
TI  - Respiratory disease, the environment, and the military: important, unexplored
      frontiers.

PMID- 18823272
TI  - Alpha-toxin facilitates the generation of CXC chemokine gradients and stimulates
      neutrophil homing in Staphylococcus aureus pneumonia.
AB  - BACKGROUND: Staphylococcus aureus alpha-toxin is a major virulence factor, but
      its mechanism of action in vivo is incompletely understood. METHODS: We examined
      the role of alpha-toxin in S. aureus pneumonia using the mouse model of
      intranasal lung infection with S. aureus strain 8325-4 (hla(+) S. aureus) and an
      alpha-toxin-deficient mutant strain made on the 8325-4 background (hla(-) S.
      aureus). RESULTS: Intranasal infection of mice with hla(-) S. aureus resulted in
      substantially less lung injury and inflammation, pulmonary edema, and tissue
      bacterial burden than did infection with hla(+) S. aureus. Furthermore, fewer
      mice infected with hla(-) S. aureus died of the infection, compared with those
      infected with hla(+) S. aureus. Levels of the CXC chemokines keratinocyte-derived
      chemokine and macrophage inflammatory protein-2 were significantly lower in the
      airways of mice infected with hla(-) S. aureus, and this difference was the
      result of reduced secretion of newly synthesized chemokines into the airway.
      Consistent with these data, significantly fewer neutrophils were present in the
      airways and lungs of mice infected with hla(-) S. aureus, compared with those
      infected with hla(+) S. aureus. CONCLUSIONS: These data suggest that alpha-toxin
      enhances virulence by facilitating the generation of CXC chemokine gradients and
      stimulating chemokine-induced neutrophil influx in S. aureus pneumonia.

PMID- 18823273
TI  - Epidemiology of vancomycin-resistant enterococci among patients on an adult stem
      cell transplant unit: observations from an active surveillance program.
AB  - OBJECTIVE: To use the findings of an active surveillance program to delineate the
      unique epidemiology of vancomycin-resistant enterococci (VRE) in a mixed
      population of transplant and nontransplant patients hospitalized on a single
      patient care unit. DESIGN: Surveillance survey and case-control analysis.
      SETTING: A 19-bed adult bone marrow and stem cell transplant unit at a referral
      and primary-care center. PATIENTS: The study included patients undergoing
      transplantation, patients who had previously received bone marrow or stem cell
      transplants, and patients with other malignancies and hematological disorders who
      were admitted to the study unit. METHODS: Patients not previously identified as
      colonized with VRE had perirectal swab specimens collected at admission and once
      weekly while hospitalized on the unit. The prevalence of VRE colonization at
      admission and the incidence throughout the hospital stay, genotypes of VRE
      specimens as determined by pulsed field gel electrophoresis, and risk factors
      related to colonization were analyzed. RESULTS: There was no significant
      difference in the prevalence or incidence of new colonization between
      nontransplant patients and prior or current transplant recipients, although
      overall prevalence at admission was significantly higher in the prior transplant
      group. Preliminary genotypic analysis of VRE isolates from transplant patients
      suggests that a proportion of cases of newly detected VRE carriage may represent
      prior colonization not detected at admission, with different risk factors
      suggestive of a potential epidemiological distinction. CONCLUSION: Examination of
      epidemiological and microbiological data collected by an active surveillance
      program provides useful information about the epidemiology of VRE that can be
      applied to inform rational infection control strategies.

PMID- 18823274
TI  - Contamination of hospital curtains with healthcare-associated pathogens.
AB  - In a culture survey, we found that 42% of hospital privacy curtains were
      contaminated with vancomycin-resistant enterococci, 22% with ethicillin-resistant
      Staphylococcus aureus, and 4% with Clostridium difficile. Hand imprint cultures
      demonstrated that these pathogens were easily acquired on hands. Hospital
      curtains are a potential source for dissemination of healthcare-associated
      pathogens.

PMID- 18823275
TI  - Evaluation of adhesion, proliferation, and functional differentiation of dermal
      fibroblasts on glycosaminoglycan-coated polysulfone membranes.
AB  - It may be hypothesized that wound healing will benefit from polymer membranes
      coated with extracellular matrix macromolecules. Here we describe the behavior of
      dermal fibroblasts on polysulfone (PSU) membranes, and PSU membranes covered with
      chitosan (Ch), chondroitin sulfate (CS), or hyaluronan, using an additional
      intermediary ionic charge modification with poly-(acrylonitrile-co-methallyl
      sulfonate) (AN69), which allows binding of the polysaccharidic macromolecules.
      Cell adhesion, proliferation, cell signaling, and collagen gene expression were
      investigated. Ch and CS were found unable to support cell adhesion and
      proliferation. In contrast, both PSU and hyaluronic acid-coated PSU membranes
      appeared as suitable materials to culture fibroblasts and support their matrix
      synthesis capacity. Moreover, they induce type III collagen expression in
      addition to type I, suggesting that they promote a fetal-like environment that
      could be beneficial for wound healing.

PMID- 18823276
TI  - Injectable tissue-engineered bone using autogenous bone marrow-derived stromal
      cells for maxillary sinus augmentation: clinical application report from a 2-6
      year follow-up.
AB  - This clinical study used injectable tissue-engineered bone, along with bone
      marrow-derived stromal cells (BMDSCs) and platelet-rich plasma (PRP), to conduct
      maxillary sinus floor augmentation by the simultaneous placement of bone graft
      and dental implants and to examine the state of regenerated bone after functional
      loading in 16 sinus augmentations in 12 patients whose alveolar crestal bone
      height was 2-10 mm. We used PRP as an autologous scaffold-which provides signal
      molecules-with in vitro expanded BMDSCs to enhance osteogenesis. All 41 dental
      implants prepared with the materials were clinically stable after second-stage
      surgery. The height of mineralized tissue at 2 years showed the mean increases of
      8.8 +/- 1.6 mm compared to preoperative values, and no adverse effects and
      remarkable bone absorption were seen in the 2-6-year follow-up time. Although
      these results are preliminary, injectable tissue-engineered bone would stably
      predict the success of bone formation and dental implants, reduce patient burden,
      and provide minimally invasive cell therapy for patients.

PMID- 18823277
TI  - Three-dimensional ingrowth of bone cells within biodegradable cryogel scaffolds
      in bioreactors at different regimes.
AB  - Three-dimensional cell ingrowth within biodegradable cryogel scaffolds made of
      cross-linked 2-hydroxyethyl methacrylate (HEMA)-lactate-dextran with
      interconnected macropores was studied in bioreactors at different regimes
      (static, perfusion, and compression-perfusion). An osteoblast-like cell line
      (MG63) was used in these studies. The samples taken after selected times from the
      bioreactors were examined by microscopy techniques (light, SEM, TEM, and laser
      scanning confocal). The cell culture conditions were found to have a significant
      impact not only on the cell morphology, such as the extent of cell attachment and
      ingrowth, but also on cellular activities. Dynamic conditions (perfusion and/or
      compression) greatly improved cell ingrowth and extracellular matrix (ECM)
      synthesis. Alkaline phosphatase activity results confirmed the positive effect of
      dynamic conditions on bone cells.

PMID- 18823278
TI  - Human chondrocyte morphology, its dedifferentiation, and fibronectin conformation
      on different PLLA microtopographies.
AB  - Surfaces of poly(L-lactic acid) (PLLA) of well-defined microtopography were
      prepared by making use of the semicrystalline character of PLLA. Different
      thermal treatments before isothermal crystallization (which include nucleation
      steps) permit to obtain a controlled number of simultaneously growing
      spherulites, which, in the end, modulate the topography at the microscale. Four
      qualitatively different surfaces were prepared. The dynamics of primary human
      chondrocyte adhesion and cytoskeleton organization was investigated on the
      different surfaces. Chondrocyte morphology is shown to be influenced by the
      microtopography of the system as obtained by scanning electron microscopy and
      atomic force microscopy (AFM). The cytoplasmatic distribution of a focal adhesion
      protein, tensin, is followed as a function of time. Since the effect of surface
      topography on cell morphology is a consequence of the process of interaction
      between the extracellular matrix (ECM) proteins, adsorbed on the surface of the
      material, and related cell adhesion molecules, the conformation of one ECM
      protein, fibronectin, adsorbed on the different substrates was investigated by
      means of AFM.

PMID- 18823279
TI  - WITHDRAWN:Curcumin, a dietary polyphenol, emerges as a novel inhibitor of DNA
      topoisomerase I of kinetoplastid parasite Leishmania donovani.
AB  - This paper published as an Immediate Publication on 29 September 2008 was
      withdrawn by the Editorial Board of the Biochemical Journal on 12 December 2008.

PMID- 18823280
TI  - Synergistic induction of nuclear factor-kappaB by transforming growth factor-beta
      and tumour necrosis factor-alpha is mediated by protein kinase A-dependent RelA
      acetylation.
AB  - The TGF-beta (transforming growth factor-beta) pathway represents an important
      signalling pathway involved in regulating diverse biological processes, including
      cell proliferation, differentiation and inflammation. Despite the critical role
      for TGF-beta in inflammatory responses, its role in regulating NF-kappaB (nuclear
      factor-kappaB)-dependent inflammatory responses still remains unknown. In the
      present study we show that TGF-beta1 synergizes with proinflammatory cytokine TNF
      alpha (tumour necrosis factor-alpha) to induce NF-kappaB activation and the
      resultant inflammatory response in vitro and in vivo. TGF-beta1 synergistically
      enhances TNF-alpha-induced NF-kappaB DNA binding activity via induction of RelA
      acetylation. Moreover, synergistic enhancement of TNF-alpha-induced RelA
      acetylation and DNA-binding activity by TGF-beta1 is mediated by PKA (protein
      kinase A). Thus the present study reveals a novel role for TGF-beta in
      inflammatory responses and provides new insight into the regulation of NF-kappaB
      by TGF-beta signalling.

PMID- 18823281
TI  - Yeast chitin synthase 2 activity is modulated by proteolysis and phosphorylation.
AB  - Saccharomyces cerevisiae Chs2 (chitin synthase 2) synthesizes the primary septum
      after mitosis is completed. It is essential for proper cell separation and is
      expected to be highly regulated. We have expressed Chs2 and a mutant lacking the
      N-terminal region in Pichia pastoris in an active form at high levels. Both
      constructs show a pH and cation dependence similar to the wild-type enzyme, as
      well as increased activity after trypsin treatment. Using further biochemical
      analysis, we have identified two mechanisms of chitin synthase regulation. First,
      it is hyperactivated by a soluble yeast protease. This protease is expressed
      during exponential growth phase, when budding cells require Chs2 activity.
      Secondly, LC-MS/MS (liquid chromatography tandem MS) experiments on purified Chs2
      identify 12 phosphorylation sites, all in the N-terminal domain. Four of them
      show the perfect sequence motif for phosphorylation by the cyclin-dependent
      kinase Cdk1. As we also show that phosphorylation of the N-terminal domain is
      important for Chs2 stability, these sites might play an important role in the
      cell cycle-dependent degradation of the enzyme, and thus in cell division.

PMID- 18823282
TI  - Characterization of the ubinuclein protein as a new member of the nuclear and
      adhesion complex components (NACos).
AB  - BACKGROUND INFORMATION: We characterized previously a cellular protein through
      its interaction with cellular and viral transcription factors from the bZip
      family. The corresponding mRNA was detected in a wide range of cell types and the
      protein was highly expressed in the nucleus of human keratinocytes. On the basis
      of these observations, we named this protein ubinuclein. RESULTS: Using a
      specific monoclonal antibody, we have shown in the present study that, although
      endogenous ubinuclein was mainly nuclear in sparse MDCK (Madin-Darby canine
      kidney) cells, it was exclusively present in the cell-cell junctions in confluent
      MDCK cultures or in polarized HT29 cells, where it co-localized with the tight
      junction marker ZO-1 (zonula occludens 1). In accordance with this, we have shown
      that ubinuclein interacted with ZO-1 in vitro and in vivo. In cultures of
      undifferentiated human keratinocytes, ubinuclein was essentially nuclear, but in
      differentiated cells, in which involucrin and periplakin reside at the apical
      cell membrane and at the cell-cell junctions, ubinuclein staining was observed at
      the lateral cell-cell borders. In human skin, ubinuclein appeared as a thread
      like pattern between the upper granular cell layer and the cornified cell layer.
      In mouse epithelia, including bile canaliculi, bronchioli, salivary gland ducts,
      and oral and olfactory epithelium, ubinuclein co-localized with tight junction
      markers. Ubinuclein was, however, not present in endothelial cell-cell junctions.
      In addition, when overexpressed, ubinuclein localized to the nucleus and
      prevented MDCK cells from entering cytokinesis, resulting in multinucleated giant
      cells after several cycles of endoreplication. CONCLUSIONS: Ubinuclein mRNA and
      its corresponding protein are expressed in almost all cell types. Analyses have
      revealed that in most cells ubinuclein occurred in the nucleoplasm, but in cells
      forming tight junctions it is recruited to the plaque structure of the zonula
      occludens. This recruitment appeared to be dependent on cell density. Therefore
      ubinuclein is a new NACos (nuclear and adhesion complex component) protein.

PMID- 18823283
TI  - Discovery of a new RNA-containing nuclear structure in UVC-induced apoptotic
      cells by integrated laser electron microscopy.
AB  - BACKGROUND INFORMATION: Treatment of cells with UVC radiation leads to the
      formation of DNA cross-links which, if not repaired, can lead to apoptosis. gamma
      H2AX and cleaved caspase 3 are proteins formed during UVC-induced DNA damage and
      apoptosis respectively. The present study sets out to identify early
      morphological markers of apoptosis using a new method of correlative microscopy,
      ILEM (integrated laser electron microscopy). Cleaved caspase 3 and gamma-H2AX
      were immunofluorescently labelled to mark the cells of interest. These cells were
      subsequently searched in the fluorescence mode of the ILEM and further analysed
      at high resolution with TEM (transmission electron microscopy). RESULTS:
      Following the treatment of HUVECs (human umbilical vein endothelial cells) with
      UVC radiation, in the majority of the cells gamma-H2AX was formed, whereas only
      in a subset of cells caspase 3 was activated. In severely damaged cells with high
      levels of gamma-H2AX a round, electron-dense nuclear structure was found, which
      was hitherto not identified in UV-stressed cells. This structure exists only in
      nuclei of cells containing cleaved caspase 3 and is present during all stages of
      the apoptotic process. Energy-loss imaging showed that the nuclear structure
      accumulates phosphorus, indicating that it is rich in nucleic acids. Because the
      nuclear structure did not label for DNA and was not affected by regressive EDTA
      treatment, it is suggested that the UV-induced nuclear structure contains a high
      amount of RNA. CONCLUSIONS: Because the UV-induced nuclear structure was only
      found in cells labelled for cleaved caspase 3 it is proposed as an electron
      microscopic marker for all stages of apoptosis. Such a marker will especially
      facilitate the screening for early apoptotic cells, which lack the well-known
      hallmarks of apoptosis within a cell population. It also raises new questions on
      the mechanisms involved in the UV-induced apoptotic pathway.

PMID- 18823284
TI  - Glucose induces an autocrine activation of the Wnt/beta-catenin pathway in
      macrophage cell lines.
AB  - The canonical Wnt signalling pathway acts by slowing the rate of ubiquitin
      mediated beta-catenin degradation. This results in the accumulation and
      subsequent nuclear translocation of beta-catenin, which induces the expression of
      a number of genes involved in growth, differentiation and metabolism. The
      mechanisms regulating the Wnt signalling pathway in the physiological context is
      still not fully understood. In the present study we provide evidence that changes
      in glucose levels within the physiological range can acutely regulate the levels
      of beta-catenin in two macrophage cell lines (J774.2 and RAW264.7 cells). In
      particular we find that glucose induces these effects by promoting an autocrine
      activation of Wnt signalling that is mediated by the hexosamine pathway and
      changes in N-linked glycosylation of proteins. These studies reveal that the
      Wnt/beta-catenin system is a glucose-responsive signalling system and as such is
      likely to play a role in pathways involved in sensing changes in metabolic
      status.

PMID- 18823285
TI  - Interdependence of two NarK domains in a fused nitrate/nitrite transporter.
AB  - Nitrate uptake is essential for various bacterial processes and combines with
      nitrite export to form the usual initial steps of denitrification, a process that
      reduces nitrate to dinitrogen gas. Although many bacterial species contain NarK
      like transporters that are proposed to function as either nitrate/proton
      symporters or nitrate/nitrite antiporters based on sequence homology, these
      transporters remain, in general, poorly characterized. Several bacteria appear to
      contain a transporter that is a fusion of two NarK-like proteins, although the
      significance of this arrangement remains elusive. We demonstrate that NarK from
      Paracoccus denitrificans is expressed as a fusion of two NarK-like transporters.
      NarK1 and NarK2 are separately capable of supporting anaerobic denitrifying
      growth but with growth defects that are partially mitigated by coexpression of
      the two domains. NarK1 appears to be a nitrate/proton symporter with high
      affinity for nitrate and NarK2 a nitrate/nitrite antiporter with lower affinity
      for nitrate. Each transporter requires two conserved arginine residues for
      activity. A transporter consisting of inactivated NarK1 fused to active NarK2 has
      a dramatically increased affinity for nitrate compared with NarK2 alone, implying
      a functional interaction between the two domains. A potential model for nitrate
      and nitrite transport in P. denitrificans is proposed.

PMID- 18823286
TI  - Malignant solitary fibrous tumour of the orbit.
AB  - PURPOSE: We aimed to report a case of orbital solitary fibrous tumour (SFT) in a
      child and to review the relevant literature. METHODS: We describe an SFT in a 13
      year-old boy with a 1-month history of painless proptosis in the left eye.
      RESULTS: Magnetic resonance imaging revealed a well circumscribed mass filling
      most of the left intraconal orbit. The lesion was excised and histopathological
      examination revealed a malignant SFT. Postoperative follow-up for 18 months was
      uneventful. CONCLUSIONS: Malignant SFT of the orbit should be included in the
      differential diagnosis of paediatric orbital tumours. Complete surgical excision
      remains the preferred method of management and the longterm prognosis is guarded.

PMID- 18823287
TI  - The prevalence of diabetic retinopathy in patients with screen-detected type 2
      diabetes in Denmark: the ADDITION study.
AB  - BACKGROUND: The prevalence of type 2 diabetes is increasing, but the exact
      prevalence of the disease and its accompanying late complications are unknown. In
      the Anglo-Danish-Dutch study of Intensive Treatment in People with Screen
      detected Diabetes in Primary Care (ADDITION study), patients with hitherto
      undiagnosed type 2 diabetes are identified using a stepwise screening strategy in
      selected general practices. This article reports the occurrence of diabetic
      retinopathy in this population. METHODS: In Arhus and Copenhagen counties, a
      total of 12,708 of the persons invited by mail were screened for diabetes
      mellitus. Consequently, 763 persons with type 2 diabetes were identified; 670 of
      these (335 from each of the two centres) underwent a general physical examination
      (including measurement of blood pressure and HbA1c) and an ophthalmological
      examination (including measurement of visual acuity and fundus photography).
      Retinopathy was graded from the photographs by counting all retinopathy lesions.
      RESULTS: Forty-five (6.8%) of the examined patients had any retinopathy, of which
      the majority was minimal. No patients had severe non-proliferative or
      proliferative diabetic retinopathy. There was no significant difference between
      age, sex and visual acuity among patients with and without retinopathy. However,
      the patients with retinopathy had significantly higher HbA1c and systolic and
      diastolic blood pressure than the patients without retinopathy. CONCLUSION:
      Patients with screen-detected diabetes have a low prevalence of diabetic
      retinopathy and no vision-threatening lesions. Screening for diabetic retinopathy
      should be focused on those patients who have already been diagnosed with type 2
      diabetes during routine clinical practice.

PMID- 18823288
TI  - Tryptophan catabolism in females with irritable bowel syndrome: relationship to
      interferon-gamma, severity of symptoms and psychiatric co-morbidity.
AB  - Irritable bowel syndrome (IBS) has been linked with abnormal serotonin
      functioning and immune activation. Tryptophan forms the substrate for serotonin
      biosynthesis, but it can alternatively be catabolized to kynurenine (Kyn) by the
      enzyme indoleamine 2,3-dioxygenase (IDO), the main inducer of which is interferon
      gamma. The primary aim of this study was to test the hypothesis that IBS is
      associated with increased tryptophan (Trp) catabolism along the Kyn pathway due
      to increased IFN-gamma levels. Plasma Kyn, Trp and IFN-gamma levels were measured
      in 41 female IBS subjects and 33 controls. Indoleamine 2,3-dioxygenase activity
      was assessed using the Kyn to Trp ratio. Psychiatric co-morbidity was assessed
      using the Patient Health Questionnaire, and severity of IBS assessed using self
      report ordinal scales. Irritable bowel syndrome subjects had increased Kyn
      concentrations compared with controls (P = 0.039) and there was a trend for
      Kyn:Trp to be increased in the IBS group (P = 0.09). There was a positive
      correlation between IBS severity and Kyn:Trp (r = 0.57, P < 0.001). Those with
      severe IBS symptoms had increased Kyn:Trp (P < 0.005) compared to those with less
      severe symptoms and controls, and were over twice as likely to have depression or
      anxiety compared to those with less severe IBS (RR = 2.2, 95% CI 1.2-3.9). No
      difference in IFN-gamma levels was observed between groups; however, IFN-gamma
      was positively correlated with Kyn:Trp in IBS (r = 0.58, P = 0.005) but not
      controls (r = 0.12, P = 0.5). Females with IBS have abnormal Trp catabolism. The
      Kyn:Trp is related to symptom severity, and those with severe IBS symptoms have
      increased shunting of Trp along the Kyn pathway which contributes to the abnormal
      serotonergic functioning in this syndrome.

PMID- 18823289
TI  - Sleep disturbances are linked to both upper and lower gastrointestinal symptoms
      in the general population.
AB  - In tertiary referral patients, there is association between altered sleep
      patterns, functional bowel disorders and altered gut motor function. Body mass
      index (BMI) is also associated with gastrointestinal (GI) symptoms including
      diarrhoea, and with sleep disturbances. Our hypothesis is that sleep disturbances
      are associated with GI symptoms, and this is not explained by BMI. A 48-item
      validated questionnaire was mailed to 6939 community participants in Olmsted
      County, MN. The survey included GI symptoms, sleep disturbance, daily lifestyle
      and quality of life (QOL). Independent contributions of sleep disturbance to
      individual symptoms were assessed using logistic regression adjusting for age,
      gender, lifestyle and mental health status. The association of an overall sleep
      score with an overall symptom score was examined and the ability of both scores
      to predict SF-12 physical and mental functioning scores assessed in multiple
      linear regression models. Among 3228 respondents, 874 (27%) reported trouble
      staying asleep. There was a significant correlation of overall sleep scores with
      overall GI symptom scores (partial r = 0.28, P < 0.001). Waking up once nightly
      at least four times a month was significantly associated with pain, nausea,
      dysphagia, diarrhoea, loose stools, urgency and a feeling of anal blockage.
      Trouble falling asleep was significantly associated with rectal urgency.
      Associations were independent of gender, age, lifestyle factors and BMI. Overall,
      sleep scores and GI symptom scores were both significant independent predictors
      of impaired QOL. In the community, reporting poor sleep is associated with upper
      and lower GI symptoms, but this is independent of BMI.

PMID- 18823290
TI  - Effect of a kappa-opioid agonist, i.v. JNJ-38488502, on sensation of colonic
      distensions in healthy male volunteers.
AB  - Kappa-opioid receptors are located on visceral pain fibres. JNJ-38488502 is a
      highly selective tetrapeptide kappa-opioid agonist with little access to the
      central nervous system and low risk of central nervous system side effects. The
      aim of the study was to evaluate the effects of i.v. JNJ-38488502 on sensations,
      including pain, during colonic distension. In a single-centre study, 23 healthy
      adult males underwent a single-dose, randomized, double-blind crossover study of
      JNJ-38488502 (0.42 mg kg(-1) i.v. infusion) vs placebo on left colon compliance,
      sensory thresholds and ratings during standard distensions. One participant could
      not undergo sensation studies. In the other 22, JNJ-38488502 increased colonic
      compliance (pressure at half-maximum volume 17.9 +/- 0.8 mmHg) compared to
      placebo (21.6 +/- 0.9 mmHg, P = 0.007). There was no significant effect on
      sensory thresholds which, however, were not reached by 44 mmHg in >50% of
      participants in both treatment phases. There were no significant treatment
      effects on sensory ratings to distensions at 8, 16, 24, 32 and 36 mmHg above
      baseline operating pressure. JNJ-38488502 was associated with increased urine
      output and plasma prolactin, consistent with kappa-opioid receptor activation.
      This study concluded that i.v. JNJ-38488502 induced kappa-opioid effects, but did
      not attenuate colonic sensations following random order colonic distension.
      Further studies of effects on pain sensations in health and disease are required.

PMID- 18823291
TI  - Endogenous and exogenous ghrelin enhance the colonic and gastric manifestations
      of dextran sodium sulphate-induced colitis in mice.
AB  - Ghrelin is an important orexigenic peptide that not only exerts gastroprokinetic
      but also immunoregulatory effects. This study aimed to assess the role of
      endogenous and exogenous ghrelin in the pathogenesis of colitis and in the
      disturbances of gastric emptying and colonic contractility during this process.
      Dextran sodium sulphate colitis was induced for 5 days in (i) ghrelin(+/+) and
      ghrelin(-/-) mice and clinical and histological parameters were monitored at days
      5, 10 and 26 and (ii) in Naval Medical Research Institute non-inbred Swiss (NMRI)
      mice treated with ghrelin (100 nmol kg(-1)) twice daily for 5 or 10 days. Neural
      contractility changes were measured in colonic smooth muscle strips, whereas
      gastric emptying was measured with the (14)C octanoic acid breath test.
      Inflammation increased ghrelin plasma levels. Body weight loss, histological
      damage, myeloperoxidase activity and IL-1beta levels were attenuated in ghrelin(
      /-) mice. Whereas absence of ghrelin did not affect changes in colonic
      contractility, gastric emptying in the acute phase was accelerated in
      ghrelin(+/+) but not in ghrelin(-/-) mice. In agreement with the studies in
      ghrelin knockout mice, 10 days treatment of NMRI mice with exogenous ghrelin
      enhanced the clinical disease activity and promoted infiltration of neutrophils
      and colonic IL-1beta levels. Unexpectedly, ghrelin treatment decreased excitatory
      and inhibitory neural responses in the colon of healthy but not of inflamed NMRI
      mice. Endogenous ghrelin enhances the course of the inflammatory process and is
      involved in the disturbances of gastric emptying associated with colitis.
      Treatment with exogenous ghrelin aggravates colitis, thereby limiting the
      potential therapeutic properties of ghrelin during intestinal inflammation.

PMID- 18823292
TI  - SPECT/CT fusion imaging in radionuclide cisternography for localization of liquor
      leakage sites.
AB  - OBJECTIVE: We report our experience with radionuclide cisternography (RC) with
      111In-diethylenthriamine penta-acetic acid (DTPA) using a computed tomography
      (CT) mounted hybrid gamma camera in patients with cerebrospinal liquor leakage.
      METHODS: SPECT/CT fusion imaging was performed in case of suspected tracer egress
      on planar or SPECT images in order to obtain a detailed correlation of the
      leakage site. RESULTS: Leakage was detected in all 3 patients. Using SPECT/CT,
      the extradural tracer accumulation could be correlated to an anatomical
      structure, which had not been possible by evaluation of the scintigraphic studies
      alone. CONCLUSION: Introducing SPECT/CT for radionuclide cisternography seems to
      be a valuable tool to facilitate the diagnosis of cerebrospinal liquor leakage.

PMID- 18823293
TI  - Real-time hemodynamic assessment of intracranial stenosis in a patient with
      orthostatic aphasia: potential applications of transcranial Doppler.
AB  - BACKGROUND: Intracranial atherosclerotic stenosis is thought to be responsible
      for 8% of all ischemic stroke subtypes. Transcranial Doppler (TCD)
      ultrasonography allows for noninvasive and dynamic evaluation of the cerebral
      circulation within the circle of Willis. We present a case of recurrent,
      orthostatic transient ischemic attacks in which, using TCD, we were able to
      correlate dynamically between the orthostatic symptomatology and a significant
      drop in the mean flow velocity (MFV) across the stenotic middle cerebral artery
      (MCA) segment. METHODS: A 56-year-old male presented with recurrent episodes of
      orthostatic right-sided weakness and expressive aphasia. Diagnostic TCD revealed
      a stenotic signal in the left internal carotid artery (ICA) siphon. Subsequent
      TCD monitoring of both MCAs demonstrated a significant orthostatic drop in MFV of
      the left MCA, which closely correlated with his symptoms. The cerebral angiogram
      confirmed a high-grade stenosis at the supraclinoid segment of the left ICA.
      CONCLUSION: TCD is a useful, noninvasive, and dynamic tool for assessment of the
      intracranial circulation, and should be considered in the workup of patients with
      hypoperfusion cerebrovascular events.

PMID- 18823294
TI  - Quantitative magnetic resonance angiography in the evaluation of the subclavian
      steal syndrome: report of 5 patients.
AB  - BACKGROUND AND PURPOSE: The indications for surgical or endovascular treatment of
      patients with subclavian stenosis (SS) or occlusion remain controversial.
      Multiple studies have shown that in most patients, SS results in steal that is
      evident radiographically, but requires no treatment. METHODS: This report
      describes 5 cases of SS, analyzed with phase contrast quantitative MRA (QMRA).
      QMRA provides quantitative blood flow data previously unavailable. A quantitative
      ischemic forearm challenge is also introduced using the QMRA technique. RESULTS:
      A basilar flow index, basilar artery (BA) flow as a percentage of total
      intracranial flow was defined. This varied from 12.6% to 20.4%. All patients in
      this report had VA flow reversal. None had BA flow reversal CONCLUSION: This
      report features novel methods using QMRA to identify ischemic patterns in the BA
      indicative of significant subclavian steal syndrome (SSS) in patients with SS.

PMID- 18823295
TI  - Neonatal and paediatric air transfers: the Isle of Man experience.

PMID- 18823297
TI  - Visual impairment is common in children born before 25 gestational weeks--boys
      are more vulnerable than girls.
AB  - INTRODUCTION: Children born extremely preterm have high risk of visual impairment
      due to retinopathy of prematurity (ROP) and cerebral lesions. OBJECTIVE: The aim
      of this study was to investigate the frequency of ROP and visual impairment as
      defined by the World Health Organization (WHO), with respect to gender in two
      hospital-based groups of children born at the limit of viability. PATIENTS AND
      METHODS: A retrospective chart review was conducted for all children (n = 114),
      born before 25 gestational weeks and screened for ROP at Karolinska hospital in
      Stockholm and Sahlgrenska hospital in Gothenburg between 1990 and 2002. Maximal
      ROP stages, treatment for ROP and visual acuity (VA), with correction when needed
      at latest available visit, were recorded. RESULTS: Altogether 97.4% had ROP,
      74.6% developed proliferative disease (stage >/= 3) and 63.2% were treated with
      retinal ablation. Normal VA (>/=0.8) in at least one eye was found in 50.5% of
      all and in significantly more girls (61.5%) than boys (34.8%) (p = 0.006), while
      visual impairment (VA < 0.33) was more common in boys (32.6%) than in girls
      (9.2%) (p = 0.004). CONCLUSION: A large proportion of children, especially boys,
      born at the level of viability are visually impaired with low vision or
      blindness. Development of preventive measures is urgent.

PMID- 18823298
TI  - Relationship of food frequencies as reported by parents to overweight and obesity
      at 5 years.
AB  - AIM: To investigate if food frequencies are related to overweight/obesity in 5
      year-old children. METHODS: During 1997-1999, 21 700 infants were invited to
      participate in ABIS (All Babies in Southeast Sweden), a prospective, cohort
      study. Participants were followed from birth (n = 16 058) to 5 years (n = 7356).
      Food frequencies reported by parents at 2.5 and 5 years were studied in the
      relation to overweight/obesity at 5 years using multiple logistic regressions. A
      p-value < 0.01 was considered statistically significant. RESULTS: At 2.5 years
      frequencies of intake of cheese were positively associated with
      overweight/obesity at 5 years while porridge, fried potatoes/french fries and
      cream/creme fraiche showed a negative association. When adjusting for known risk
      factors, porridge and fried potatoes/french fries remained negatively associated
      with overweight/obesity. At 5 years, chocolate and lemonade were positively
      associated with overweight/obesity whereas cream/creme fraiche, pastries and
      candy were negatively associated. Candy remained negatively associated to
      overweight/obesity after adjustment for potential confounders. CONCLUSION: Food
      frequencies do not offer any simple explanation for overweight/obesity. Porridge
      at 2.5 years may protect against overweight/obesity at 5 years, while lemonade
      may contribute to overweight. Our finding that fried potatoes/french fries may
      protect against overweight/obesity is unexpected and must be interpreted with
      caution. These findings should be confirmed by prospective studies using
      objective recordings.

PMID- 18823299
TI  - Evaluation of the pharmacokinetics of digoxin in healthy subjects receiving
      etoricoxib.
AB  - AIMS: Digoxin is a commonly prescribed cardiac glycoside with a narrow
      therapeutic index. The aim was to investigate whether the cyclooxygenase-2
      selective nonsteroidal anti-inflammatory drug etoricoxib affects the steady-state
      pharmacokinetics of digoxin. METHODS: This was a double-blind, randomized,
      placebo-controlled, two-period cross-over study. In each period, 14 healthy
      volunteers ranging in age from 21 to 35 years received oral digoxin 0.25 mg daily
      and were randomized to either etoricoxib 120 mg or matching placebo tablets once
      daily for 10 days. Trough digoxin plasma concentrations were analysed by linear
      regression to examine digoxin accumulation over time. RESULTS: The geometric mean
      ratios (etoricoxib/placebo) for AUC(0-24h), C(max) and urinary excretion were
      1.06 (90% confidence interval 0.97, 1.17), 1.33 (1.21, 1.46) and 1.10 (1.00,
      1.20), respectively. The median (range) for digoxin T(max) (h) values with
      etoricoxib and placebo were 0.5 (0.5, 1.5) and 1.0 (0.5, 1.5), respectively.
      Steady-state digoxin plasma concentrations were achieved by day 7 in each
      treatment period. No serious adverse experiences were reported. CONCLUSIONS:
      Although etoricoxib 120 mg did produce an approximately 33% increase in digoxin
      C(max), this increase does not appear to be clinically meaningful, as
      cardiotoxicity with digoxin has been associated with elevations in steady-state
      rather than peak concentrations. From these results, it appears that etoricoxib
      does not cause any changes in digoxin steady-state pharmacokinetics that would
      necessitate a dose adjustment.

PMID- 18823300
TI  - Do thiazide diuretics alter the pharmacokinetics of metformin in patients with
      type 2 diabetes already established on metformin?

PMID- 18823301
TI  - Psychological, social and behavioural factors that influence drug efficacy: a
      noteworthy research subject in clinical pharmacology.

PMID- 18823302
TI  - Macrolide-theophylline interactions: no role for the inhibition of cytochrome
      P4501A2.

PMID- 18823303
TI  - QT prolongation and torsade de pointes associated with solifenacin in an 81-year
      old woman.

PMID- 18823304
TI  - The effect of SLCO1B1 polymorphism on repaglinide pharmacokinetics persists over
      a wide dose range.
AB  - AIMS: To establish whether the effect of SLCO1B1[encoding organic anion
      transporting polypeptide 1B1 (OATP1B1)] c.521T-->C (p.Val174Ala) polymorphism on
      the pharmacokinetics of repaglinide is dose-dependent. METHODS: Twelve healthy
      volunteers with the SLCO1B1 c.521TT genotype (controls) and eight with the
      c.521CC genotype ingested a single 0.25-, 0.5-, 1- or 2-mg dose of repaglinide in
      a dose-escalation study with a wash-out period of > or =1 week. RESULTS: The mean
      area under the plasma concentration-time curve from time 0 to infinity (AUC(0
      infinity)) of 0.25, 0.5, 1 or 2 mg repaglinide was 82% (95% confidence interval
      47, 125), 72% (24, 138), 56% (24, 95) or 108% (59, 171) (P < or = 0.001) larger
      in participants with the SLCO1B1 c.521CC genotype than in those with the c.521TT
      genotype, respectively. Repaglinide peak plasma concentration and AUC(0-infinity)
      increased linearly along with repaglinide dose in both genotype groups (r > 0.88,
      P < 0.001). There was a tendency towards lower blood glucose concentrations after
      repaglinide administration in the participants with the c.521CC genotype than in
      those with the c.521TT genotype. CONCLUSIONS: The effect of SLCO1B1 c.521T-->C
      polymorphism on the pharmacokinetics of repaglinide persists throughout the
      clinically relevant dose range.

PMID- 18823305
TI  - Initiation and persistence with clopidogrel treatment after acute myocardial
      infarction: a nationwide study.
AB  - AIMS: To identify possible underuse by analysing initiation and persistence with
      clopidogrel treatment in an unselected population of patients admitted with
      myocardial infarction (MI) with or without subsequent percutaneous coronary
      intervention (PCI). METHODS: Patients admitted with first-time MI from 2000 to
      2005 and subsequent prescription claims of clopidogrel were identified by
      individual-level linkage of nationwide administrative registries in Denmark.
      Independent factors affecting initiation and persistence with treatment were
      analysed by multivariable logistic regression models and Cox proportional hazard
      models. RESULTS: A total of 46,190 MI patients were included in the study, of
      whom 14,939 were treated with PCI. From 2000 to 2005 initiation of clopidogrel
      increased from 80.4 to 93.7% among MI patients with PCI and from 2.8 to 39.3%
      among MI patients without PCI. MI patients with concomitant heart failure
      received less treatment [odds ratio (OR) 0.49, confidence interval (CI) 0.43,
      0.56 among patients with PCI and OR 0.90, CI 0.81, 0.99 among patients without
      PCI in 2002-2003, and OR 0.89, CI 0.80, 1.00 in 2004-2005, respectively]. Of MI
      patients with PCI, 77.5% completed 9 months' clopidogrel treatment in 2004-2005,
      the corresponding figures for MI patients without PCI being 53.9%. CONCLUSIONS:
      Initiation and persistence with clopidogrel treatment is high in MI patients with
      PCI. However, we found substantial underuse among MI patients without PCI and in
      MI patients with heart failure.

PMID- 18823306
TI  - Population pharmacokinetic and pharmacogenetic analysis of 6-mercaptopurine in
      paediatric patients with acute lymphoblastic leukaemia.
AB  - AIMS: To investigate the population pharmacokinetics of 6-mercaptopurine (6-MP)
      active metabolites in paediatric patients with acute lymphoblastic leukaemia
      (ALL) and examine the effects of various genetic polymorphisms on the disposition
      of these metabolites. METHODS: Data were collected prospectively from 19
      paediatric patients with ALL (n = 75 samples, 150 concentrations) who received 6
      MP maintenance chemotherapy (titrated to a target dose of 75 mg m(-2) day(-1)).
      All patients were genotyped for polymorphisms in three enzymes involved in 6-MP
      metabolism. Population pharmacokinetic analysis was performed with the nonlinear
      mixed effects modelling program (nonmem) to determine the population mean
      parameter estimate of clearance for the active metabolites. RESULTS: The
      developed model revealed considerable interindividual variability (IIV) in the
      clearance of 6-MP active metabolites [6-thioguanine nucleotides (6-TGNs) and 6
      methylmercaptopurine nucleotides (6-mMPNs)]. Body surface area explained a
      significant part of 6-TGNs clearance IIV when incorporated in the model (IIV
      reduced from 69.9 to 29.3%). The most influential covariate examined, however,
      was thiopurine methyltransferase (TPMT) genotype, which resulted in the greatest
      reduction in the model's objective function (P < 0.005) when incorporated as a
      covariate affecting the fractional metabolic transformation of 6-MP into 6-TGNs.
      The other genetic covariates tested were not statistically significant and
      therefore were not included in the final model. CONCLUSIONS: The developed
      pharmacokinetic model (if successful at external validation) would offer a more
      rational dosing approach for 6-MP than the traditional empirical method since it
      combines the current practice of using body surface area in 6-MP dosing with a
      pharmacogenetically guided dosing based on TPMT genotype.

PMID- 18823307
TI  - Life-threatening hypokalaemia and lactate accumulation after autointoxication
      with Stacker 2, a 'powerful slimming agent'.

PMID- 18823308
TI  - Allergens to wheat and related cereals.
AB  - Wheat is one of the major crops grown, processed and consumed by humankind and is
      associated with both intolerances (notably coeliac disease) and allergies. Two
      types of allergy are particularly well characterized. The first is bakers'
      asthma, which results from the inhalation of flour and dust during grain
      processing. Although a number of wheat proteins have been shown to bind IgE from
      patients with bakers' asthma, there is no doubt a well-characterized group of
      inhibitors of alpha-amylase (also called chloroform methanol soluble, or CM,
      proteins) are the major components responsible for this syndrome. The second well
      characterized form of allergy to wheat proteins is wheat-dependent exercise
      induced anaphylaxis (WDEIA), with the omega(5)-gliadins (part of the gluten
      protein fraction) being the major group of proteins which are responsible. Other
      forms of food allergy have also been reported, with the proteins responsible
      including gluten proteins, CM proteins and non-specific lipid transfer proteins.
      Processing of wheat and of related cereals (barley and rye, which may contain
      related allergens) may lead to decreased allergenicity while genetic engineering
      technology offers opportunities to eliminate allergens by suppressing gene
      expression.

PMID- 18823310
TI  - Effects of Lactobacillus GG treatment during pregnancy on the development of
      fetal antigen-specific immune responses.
AB  - BACKGROUND: Several clinical trials suggest that probiotics may have a role in
      the prevention of eczema. The optimal timing and mechanisms underlying this
      intervention are not clear. In particular it is not known whether such treatment
      works during pregnancy or whether postnatal exposure is important. OBJECTIVE: We
      investigated whether the probiotic Lactobacillus rhamnosus strain GG (LGG)
      influences fetal immune responses when administered to pregnant women, as a
      possible mechanism for its protective effects against the development of eczema.
      METHODS: Peripheral blood mononuclear cell from 11 adults treated with LGG, and
      cord blood mononuclear cells (CBMCs) from 73 women participating in a randomized
      controlled trial of LGG treatment were cultured with heat-killed LGG, ovalbumin
      (OVA) or without stimulus. Cells were analysed by flow cytometry and real-time
      PCR for markers of dendritic cell (DC) phenotype, T cell proliferation and
      regulation. Cytokine secretion was analysed in culture supernatants by multiplex
      cytokine assay. RESULTS: LGG treatment of adults led to systemic immune responses
      suggestive of antigen-specific tolerance including reduced CD4(+) T cell
      proliferation to heat-killed LGG (30% reduction; P=0.03). LGG treatment of
      pregnant women did not influence CD4(+) T cell proliferation, forkhead box P3
      expression, DC phenotype or cytokine secretion in CBMCs cultured with heat-killed
      LGG or OVA. CONCLUSION: LGG treatment of pregnant women fails to influence fetal
      antigen-specific immune responses. This suggests that modulation of fetal immune
      responses may not be a major mechanism by which probiotics such as LGG prevent
      eczema.

PMID- 18823309
TI  - Association of polymorphisms in CASP10 and CASP8 with FEV(1)/FVC and bronchial
      hyperresponsiveness in ethnically diverse asthmatics.
AB  - BACKGROUND: Several chromosomal regions have been identified using family-based
      linkage analysis to contain genes contributing to the development of asthma and
      allergic disorders. One of these regions, chromosome 2q32-q33, contains a gene
      cluster containing CFLAR, CASP10 and CASP8. These genes regulate the extrinsic
      apoptosis pathway utilized by several types of immune and structural cells that
      have been implicated in the pathogenesis of asthma. OBJECTIVE: To assess the role
      of genetic variation in CFLAR, CASP10 and CASP8 in asthma and related phenotypes
      in individuals of diverse ethnic backgrounds. METHODS: We tested 26 single
      nucleotide polymorphisms (SNPs) in the CFLAR, CASP10 and CASP8 gene cluster for
      association with asthma and related phenotypes in African-American, non-Hispanic
      whites, and Hispanic case-control populations (cases, N=517, controls, N=644).
      RESULTS: Five CASP10 SNPS were associated with forced expiratory volume in 1 s
      (FEV(1))/forced expiration volume capacity (FVC) in the African-American subjects
      with asthma (P=0.0009-0.047). Nine SNPs, seven in CASP10 and two in CASP8, were
      also associated with the degree of bronchial hyperresponsiveness (BHR) (as
      determined by PC(20)) in race-specific analysis, predominately in the Non
      Hispanic white cases. Two SNPs, rs6750157 in CASP10 and rs1045485 in CASP8 were
      modestly associated with asthma in the African-American (P=0.025) and Hispanic
      (P=0.033) populations, respectively. CONCLUSION: These data suggest a role for
      CASP10 as a potential modifier of the asthma phenotype, specifically with
      measures of airway obstruction and BHR.

PMID- 18823311
TI  - Validation of the triage risk stratification tool to identify older persons at
      risk for hospital admission and returning to the emergency department.
AB  - OBJECTIVES: To assess the predictive validity of the Triage Risk Stratification
      Tool (TRST) to identify return to the emergency department (ED) or
      hospitalization in a multicenter patient sample. DESIGN: Prospective,
      observational study with 1-year follow-up. SETTING: EDs of three hospitals in
      Toronto, Canada. PARTICIPANTS: Seven hundred eighty-eight subjects aged 65 to 101
      (mean age 76.6, 58.5% female) who presented to the ED and were discharged home
      from the ED. MEASUREMENTS: Trained clinical assessors completed the TRST on
      patients aged 65 and older during a 4-week study period. Patients who
      subsequently returned to the ED or were admitted to the hospital were identified
      using hospital information systems and classified as experiencing the composite
      endpoint at 30, 120, and 365 days. RESULTS: The mean TRST score was 1.55 (range 0
      5), and 147 (18.7%) patients experienced the composite endpoint of return to the
      ED or hospital admission by 30 days. The sensitivity of a TRST score of 2 or
      greater was 62%, (95% confidence interval (CI)=54-70%), specificity was 57% (95%
      CI=53-61%), and likelihood ratio was 1.44 (95% CI=1.23-1.66). The area under the
      curve was 0.61 using a cutoff score of 2. CONCLUSION: The TRST demonstrated only
      moderate predictive ability, and ideally, a better prediction rule should be
      sought. Future studies to develop better prediction rules should compare their
      performance with that of existing prediction rules, including the TRST and
      Identifying Seniors at Risk tool, and assess the effect of any new prediction
      rule on patient outcomes.

PMID- 18823312
TI  - Arabidopsis thaliana acyl-CoA-binding protein ACBP2 interacts with heavy-metal
      binding farnesylated protein AtFP6.
AB  - Arabidopsis thaliana acyl-CoA-binding protein 2 (ACBP2) was observed to interact
      with farnesylated protein 6 (AtFP6), which has a metal-binding motif (M/LXCXXC).
      Their interaction and expression in response to heavy metals were investigated.
      Yeast two-hybrid analysis and in vitro assays showed that an ACBP2 derivative
      lacking ankyrin repeats did not interact with AtFP6, indicating that the ankyrin
      repeats mediate protein-protein interaction. Autofluorescence-tagged ACBP2 and
      AtFP6 transiently co-expressed in tobacco (Nicotiana tabacum) were both targeted
      to the plasma membrane. Reverse transcriptase polymerase chain reaction and
      northern blot analyses revealed that AtFP6 mRNA was induced by cadmium (Cd(II))
      in A. thaliana roots. Assays using metal-chelate affinity chromatography
      demonstrated that in vitro translated ACBP2 and AtFP6 bound lead (Pb(II)), Cd(II)
      and copper (Cu(II)). Consistently, assays using fluorescence analysis confirmed
      that (His)(6)-AtFP6 bound Pb(II), like (His)(6)-ACBP2. Arabidopsis thaliana
      plants overexpressing ACBP2 or AtFP6 were more tolerant to Cd(II) than wild-type
      plants. Plasma membrane-localized ACBP2 and AtFP6 probably mediate Pb(II), Cd(II)
      and Cu(II) transport in A. thaliana roots. Also, (His)(6)-ACBP2 binds
      [(14)C]linoleoyl-CoA and [(14)C]linolenoyl-CoA, the precursors for phospholipid
      repair following lipid peroxidation under heavy metal stress at the plasma
      membrane. ACBP2-overexpressing plants were more tolerant to hydrogen peroxide
      than wild-type plants, further supporting a role for ACBP2 in post-stress
      membrane repair.

PMID- 18823313
TI  - Virus infection improves drought tolerance.
AB  - Viruses are obligate intracellular symbionts. Plant viruses are often discovered
      and studied as pathogenic parasites that cause diseases in agricultural plants.
      However, here it is shown that viruses can extend survival of their hosts under
      conditions of abiotic stress that could benefit hosts if they subsequently
      recover and reproduce. Various plant species were inoculated with four different
      RNA viruses, Brome mosaic virus (BMV), Cucumber mosaic virus (CMV), Tobacco
      mosaic virus and Tobacco rattle virus. The inoculated plants were stressed by
      withholding water. The onset of drought symptoms in virus-infected plants was
      compared with that in the plants that were inoculated with buffer (mock
      inoculated plants). Metabolite profiling analysis was conducted and compared
      between mock-inoculated and virus-infected plants before and after being
      subjected to drought stress. In all cases, virus infection delayed the appearance
      of drought symptoms. Beet plants infected with CMV also exhibited significantly
      improved tolerance to freezing. Metabolite profiling analysis showed an increase
      in several osmoprotectants and antioxidants in BMV-infected rice and CMV-infected
      beet plants before and after drought stress. These results indicate that virus
      infection improves plant tolerance to abiotic stress, which correlates with
      increased osmoprotectant and antioxidant levels in infected plants.

PMID- 18823314
TI  - The phytotoxin coronatine induces light-dependent reactive oxygen species in
      tomato seedlings.
AB  - The phytotoxin coronatine (COR), which is produced by Pseudomonas syringae pv.
      tomato DC3000 (DC3000), has multiple roles in virulence that lead to chlorosis
      and a reduction in chlorophyll content. However, the physiological significance
      of COR-induced chlorosis in disease development is still largely unknown. Global
      expression analysis demonstrated that DC3000 and COR, but not the COR-defective
      mutant DB29, caused reduced expression of photosynthesis-related genes and result
      in a 1.5- to 2-fold reduction in maximum quantum efficiency of photosystem II
      (F(V)/F(M)). Tomato (Solanum lycopersicum) seedlings inoculated with DC3000 and
      incubated in a long daily photoperiod showed more necrosis than inoculated
      seedlings incubated in either dark or a short daily photoperiod. The accumulation
      of reactive oxygen species (ROS) was detected in cotyledons inoculated with
      either purified COR or DC3000 but not in tissues inoculated with DB29.
      Interestingly, COR-induced ROS accumulated only in light and was inhibited by 3
      (3,4-dichlorophenyl)-1,1-dimethylurea and diphenylene iodonium, which function to
      inhibit electron transport from PSII. Furthermore, COR and DC3000 suppressed
      expression of the gene encoding the thylakoid Cu/Zn superoxide dismutase but not
      the cytosolic form of the same enzyme. In conclusion, these results demonstrate a
      role for COR-induced effects on photosynthetic machinery and ROS in modulating
      necrotic cell death during bacterial speck disease of tomato.

PMID- 18823315
TI  - Copper stress induces biosynthesis of octadecanoid and eicosanoid oxygenated
      derivatives in the brown algal kelp Laminaria digitata.
AB  - To better understand the toxicity and the orchestration of antioxidant defenses
      of marine brown algae in response to copper-induced stress, lipid peroxidation
      processes were investigated in the brown alga Laminaria digitata. The expression
      of genes involved in cell protection and anti-oxidant responses were monitored by
      semi-quantitative reverse transcriptase polymerase chain reaction and the lipid
      peroxidation products were further characterized by profiling oxylipin signatures
      using high-pressure liquid chromatography-mass spectrometry. Exposure to copper
      excess triggers lipoperoxide accumulation and upregulates the expression of
      stress related genes. It also increases the release of free polyunsaturated fatty
      acids, leading to an oxidative cascade through at least two distinct mechanisms.
      Incubations in presence of inhibitors of lipoxygenases and cycloxygenases showed
      that in addition to the reactive oxygen species-mediated processes, copper stress
      induces the synthesis of oxylipins through enzymatic mechanisms. Among complex
      oxylipins, cyclopentenones from C18 and C20 fatty acids such as 12-oxo-PDA and
      prostaglandins were detected for the first time in brown algae, as well as unique
      compounds such as the 18-hydroxy-17-oxo-eicosatetraenoic acid. These results
      suggest that lipid peroxidation participates in the toxic effects of copper and
      that lipid peroxidation derivatives may regulate protective mechanisms by
      employing plant-like octadecanoid signals but also eicosanoid oxylipins which are
      absent in vascular plants.

PMID- 18823316
TI  - Genital responsiveness in healthy women--what about subjective genital
      engorgement?

PMID- 18823317
TI  - Lack of information underlies women's perceptions of erectile dysfunction (ED)
      drugs in Japan.
AB  - INTRODUCTION: Some Japanese women are known to have negative attitudes toward
      erectile dysfunction (ED) drugs, but the environment underlying these perceptions
      is unclear. AIM: To reveal the underlying environment that shapes women's
      perceptions of ED drugs in Japan. METHODS: A web-based questionnaire was
      conducted through an Internet-based market research company. A total of 2,593
      women in five age groups (20s, 30s, 40s, 50s, and 60s or older) were randomly
      invited to participate in this study, with an almost equal number in each age
      group. The questionnaire contained 30 items related to individual background and
      sexual information, concerns about the image of ED drugs, ED drug-related
      perceptions, and attitude toward sexual information media. MAIN OUTCOME MEASURES:
      The women's attitude and the independent predictors that affect their partner's
      use of ED drugs were clarified. RESULTS: Answers were obtained from 1,077 women,
      of whom 35.4% (n=381) had a negative image of ED drugs. Although 69.5% (n=749)
      agreed that a sexual relationship with a male partner was important, only 26.7%
      (n=288) agreed that this remained important if ED drugs were used. However, 56.7%
      (n=611) and 57.7% (n=621) of respondents, respectively, answered that they would
      allow their partner's use of ED drugs if they imagined that they understood the
      safety and effectiveness of ED drugs and that their quality of life was improved
      by their partner's use of the drugs. Lack of information about ED drugs was a
      significant predictor for acceptance of a partner's use of ED drugs among women
      with a negative image of ED drugs, since they were more likely to accept the use
      of these drugs if they were convinced about their safety and effectiveness or
      positive effect on quality of life. CONCLUSION: Lack of information about ED
      drugs may influence the perception of women in Japan regarding these drugs.

PMID- 18823318
TI  - The PDE5 inhibitor sildenafil increases circulating endothelial progenitor cells
      and CXCR4 expression.
AB  - INTRODUCTION: Endothelial progenitor cells (EPC) are a specific subtype of
      progenitor cells that can be isolated from circulating mononuclear cells, able to
      migrate from the bone marrow to the peripheral circulation where they contribute
      to vascular repair. CXC-motif chemochine receptor 4 (CXCR4) receptor seems to
      play a critical role in this process. AIM: To assess the effects of sildenafil (a
      type 5 phosphodiesterase [PDE5] inhibitor) administration in 20 healthy young
      men. METHODS: Evaluation of CXCR4 expression in circulating EPC before and 4
      hours after in vivo administration of 100 mg sildenafil by flow cytometry and
      colony-forming unit. RESULTS: We found that sildenafil increases circulating EPC
      number, the relative expression of CXCR4 on these cells and the ability to
      generate colonies in vitro. CONCLUSIONS: These data allow us to suppose an
      involvement of PDE5 in bone marrow release and peripheral homing of EPC.

PMID- 18823319
TI  - Salmonella infection of a penile prosthesis.
AB  - INTRODUCTION: Patients with erectile dysfunction (ED) who have failed oral or
      intracavernosal erectogenic therapy may benefit from inflatable penile prosthesis
      (IPP) placement. Such individuals commonly include patients with diabetes
      mellitus or chronic renal insufficiency. Complications of IPP placement include
      erosion and infection. Most often, infection of IPPs involves skin flora that are
      hypothesized to be introduced at the time of device placement and persist as a
      biofilm, causing clinical infection as a result of failure of containment by host
      defense mechanisms. AIM: In this report, we describe a renal transplant patient
      with a Salmonella infection of an IPP following a diarrheal illness. To our
      knowledge, this organism has not been implicated in penile prosthesis infection.
      MAIN OUTCOME MEASURES: The clinical course of, and microbiological data pertinent
      to, this patient are summarized. Additionally, a limited literature review was
      undertaken and is here summarized. METHODS: Retrospective review of medical
      record documentation. RESULTS: This patient was found to have a Salmonella
      infection of his IPP with ensuing device erosion. Following urgent device removal
      and culture-specific antibiotic therapy, he was discharged from the hospital at
      his baseline functional status and renal function. CONCLUSIONS: This is the first
      report of which we are aware in which Salmonella penile prosthesis infection is
      described. While this man's immunocompromised status may have made him more
      vulnerable to device infection, the literature is generally supportive of IPP
      placement in the transplant population when other modes of ED treatment have
      failed. Moreover, we postulate a hematogenous mechanism for device seeding in
      this patient.

PMID- 18823320
TI  - Activation of the ET-1/ETA pathway contributes to erectile dysfunction associated
      with mineralocorticoid hypertension.
AB  - INTRODUCTION: The cavernosal tissue is highly responsive to endothelin-1 (ET-1),
      and penile smooth muscle cells not only respond to but also synthesize ET-1. AIM:
      Considering that ET-1 is directly involved in end-organ damage in salt-sensitive
      forms of hypertension, we hypothesized that activation of the ET-1/ET(A) receptor
      pathway contributes to erectile dysfunction (ED) associated with
      mineralocorticoid hypertension. METHODS: Wistar rats were uninephrectomized and
      submitted to deoxycorticosterone acetate (DOCA)-salt treatment for 5 weeks.
      Control (Uni [uninephrectomized control]) animals were uninephrectomized and
      given tap water. Uni and DOCA-salt rats were simultaneously treated with vehicle
      or atrasentan (ET(A) receptor antagonist, 5 mg/Kg/day). Cavernosal reactivity to
      ET-1, phenylephrine (PE), ET(B) receptor agonist (IRL-1620) and electric field
      stimulation (EFS) were evaluated in vitro. Expression of ROCKalpha, ROCKbeta,
      myosin phosphatase target subunit 1 (MYPT-1), and extracellular signal-regulated
      kinase 1/2 (ERK 1/2) were evaluated by western blot analysis. ET-1 and ET(A)
      receptor mRNA expression was evaluated by real-time reverse-transcriptase
      polymerase chain reaction. Voltage-dependent increase in intracavernosal
      pressure/mean arterial pressure (ICP/MAP) was used to evaluate erectile function
      in vivo. MAIN OUTCOME MEASURE: ET(A) receptor blockade prevents DOCA-salt
      associated ED. RESULTS: Cavernosal strips from DOCA-salt rats displayed augmented
      preproET-1 expression, increased contractile responses to ET-1 and decreased
      relaxation to IRL-1620. Contractile responses induced by EFS and PE were enhanced
      in cavernosal tissues from DOCA-salt hypertensive rats. These functional changes
      were associated with increased activation of the RhoA/Rho-kinase and ERK 1/2
      pathways. Treatment of rats with atrasentan completely prevented changes in
      cavernosal reactivity in DOCA-salt rats and restored the decreased ICP/MAP,
      completely preventing ED in DOCA-salt rats. CONCLUSION: Activation of the ET
      1/ET(A) pathway contributes to mineralocorticoid hypertension-associated ED.
      ET(A) receptor blockade may represent an alternative therapeutic approach for ED
      associated with salt-sensitive hypertension and in pathological conditions where
      increased levels of ET-1 are present.

PMID- 18823321
TI  - Development and evaluation of the Women's Sexual Interest Diagnostic Interview
      (WSID): a structured interview to diagnose hypoactive sexual desire disorder
      (HSDD) in standardized patients.
AB  - INTRODUCTION: Female sexual dysfunction (FSD) is a common disorder in
      postmenopausal women. Currently, there is no clear "gold standard" for the
      diagnosis of FSD. AIM: The aim of this study was to evaluate the interrater
      reliability of the Women's Sexual Interest Diagnostic Interview (WSID), a new
      structured clinical interview designed to diagnose hypoactive sexual desire
      disorder (HSDD). The reliability of additional interview questions focused on the
      diagnosis of other types of FSD was also evaluated. MAIN OUTCOME MEASURES: The
      main outcome measure was the level of agreement in the diagnosis of FSD among
      clinical experts, between clinical experts and study coordinators, and between
      clinical experts and patients' self-reported interactive voice response system
      (IVRS) version of the WSID. METHODS: Two versions of WSID were developed based on
      current diagnostic criteria: a clinician-administered version using a structured
      interview guide, and a patient self-report version using an IVRS. Three sexual
      medicine experts developed 20 clinical scenarios portraying cases and noncases of
      HSDD and other FSD diagnostic subtypes. Ten actresses with experience in
      standardized patient interviewing rehearsed these scenarios and performed the
      scripted patient roles in a standardized clinical interview with clinical experts
      (not the author of the script) and study coordinators, on a one-on-one basis,
      using the WSID interview format. In addition, all actresses completed the IVRS
      version of the WSID. Interviews were videotaped and viewed by the expert panel.
      In each instance, the diagnosis that the interview was scripted to portray was
      considered as the "gold standard." Kappa (kappa) coefficients were utilized to
      assess the level of agreement among experts, between study coordinators and the
      "gold standard", and between the IVRS version of the WSID and the "gold
      standard". RESULTS: All experts agreed with the gold standard diagnosis provided
      by the author of the script (kappa=1.0). Similarly, there was perfect agreement
      among the experts on the presence of depressive symptomatology (kappa=1.0). On
      the related diagnoses of arousal disorder, orgasmic disorder, and sexual pain
      disorder, kappas of 0.894, 0.966, and 0.946 were observed (P<0.0001 for all
      comparisons). When study coordinator's WSID diagnoses were compared with the
      "gold standard," kappa for HSDD was 0.851; sensitivity was 0.864, and specificity
      and positive predictive value (PPV) were 1.00 (P<0.001 for all comparisons). When
      diagnoses obtained via IVRS interviews were compared with the "gold standard",
      kappa for HSDD was 0.802, sensitivity was 0.818, and specificity and PPV were
      1.00 (P<0.001 for all comparisons). CONCLUSION: Agreement as estimated by kappa
      coefficients was consistently high in both clinician-administered and patient
      self-reported IVRS versions in the diagnosis of HSDD.

PMID- 18823322
TI  - Glucose-6-phosphate dehydrogenase deficiency associated stuttering priapism:
      report of a case.
AB  - AIM: Stuttering priapism is an uncommon form of recurrent priapism whose etiology
      if often unknown. To date, there has been one report of a patient with stuttering
      priapism and glucose-6-phosphate dehydrogenase (G6PD) deficiency. Herein we
      describe the second-known case of recurrent priapism in a patient with G6PD
      deficiency. The pathophysiology of G6PD deficiency and its potential to cause
      priapism is reviewed. METHODS: A case report is described of a 29-year-old
      African-American man with G6PD deficiency who presented with numerous episodes of
      recurrent ischemic priapism. Clinical data was reviewed. RESULTS: Despite medical
      management with gonadotropin-releasing hormone (GnRH) agonist, an antiandrogen,
      and baclofen, he required several surgical procedures which also ultimately
      failed. A continuous phosphodiesterase type-5 inhibitor (PDE5) was started and
      the patient had no recurrences at 3-month follow-up. CONCLUSION: Idiopathic
      recurrent priapism may be explained by underlying hemolytic anemia associated
      with G6PD deficiency. Several possible mechanisms exist to explain this
      association, including hyperviscosity, direct endothelial dysfunction secondary
      to bare hemoglobin vasculotoxicity, and relative nitric oxide deficiency causing
      vasoconstriction and vascular smooth muscle proliferation.

PMID- 18823323
TI  - Needs assessment survey to justify establishing a reproductive health clinic at a
      comprehensive cancer center.
AB  - INTRODUCTION: Reproductive health problems, including sexual dysfunction and
      impaired fertility, are distressing and persistent after cancer treatment.
      However, recent reports suggest that reproductive health remains neglected in
      oncology settings. AIMS: We conducted a survey to ascertain the prevalence of
      reproductive health problems in men and women treated in a comprehensive cancer
      center, and to estimate potential usage of clinical services to preserve
      fertility or to treat postcancer infertility and sexual dysfunction. METHODS: We
      mailed 800 questionnaires to men and women treated for cancer at our institution
      1 to 5 years previously. Cancer sites and ages were chosen to maximize the risk
      of reproductive problems. We stratified the sample by living distance from our
      institution, to see if travel affected service utlilization. To provide a self
      selected sample for comparison, another 200 questionnaires were made available in
      outpatient areas. MAIN OUTCOME MEASURES: Self-report questionnaire. RESULTS: The
      return rate for the combined surveys was 29% for men and 26% for women. Cancer
      sites for self-selected respondents were almost identical to those in the postal
      cohort. Prevalence and types of sexual dysfunction were typical for surveys of
      cancer survivors, with 49% of men reporting new erection problems after cancer
      treatment and 45% of women noting loss of desire for sex and vaginal dryness.
      About a third of patients aged less than 50 years would have liked a fertility
      consultation before cancer treatment. Twenty to thirty percent wanted more
      information about premature ovarian failure or health risks for their children.
      Twenty-four percent of men and 21% of women would definitely want to visit a
      reproductive health clinic in the next year. Factors associated with wanting an
      appointment included self-selection to complete the survey and, for men, having
      less education. CONCLUSION: It should be feasible to establish a
      multidisciplinary reproductive health center in a comprehensive cancer center.

PMID- 18823324
TI  - The sexual lives of residents and fellows in graduate medical education programs:
      a single institution survey.
AB  - INTRODUCTION: The prevalence of sexual problems among resident physicians has not
      been investigated. AIM: To explore the sexual behavior of residents and fellows
      in training and to determine the incidence of sexual dysfunction in this
      population. METHODS: Residents and fellows at our institution were invited to
      complete a demographic questionnaire, as well as two to three gender-specific
      validated instruments for the assessment of human sexuality. MAIN OUTCOME
      MEASURES: The validated survey instruments selected were the International Index
      of Erectile Function (IIEF), the Index of Premature Ejaculation (IPE), and the
      Self-Esteem and Relationship Quality (SEAR) survey for male residents, and the
      Female Sexual Function Index (FSFI) and the Index of Sex Life (ISL) for female
      residents. Results were compared with established normative data and validated
      cut-off scores that were available. Pearson correlation coefficient was used to
      assess for relationships between variables. RESULTS: There were 180 responses (83
      female, 97 male, mean age 29 years), for a response rate of 20%. Among men, 90%,
      67%, and 98% were in a relationship, married, and heterosexual, respectively.
      Among women, the same numbers were 80%, 55%, and 96%, respectively. Based on
      validated cut-off scores for the IIEF and FSFI, 13% of men reported ED (3%
      reported mild ED, 4% reported moderate ED, and 6% reported severe ED) and 60% of
      women were classified as "at high risk" for sexual problems, with desire
      disorders the most prevalent and orgasmic disorders the second most prevalent.
      There were significant gender differences with respect to the associations
      between sexual and relationship problems. CONCLUSIONS: Sexual problems may be
      prevalent among residents in training, particularly female residents. Additional,
      larger studies that assess other quality of life measures and query sexual
      partners of residents are needed.

PMID- 18823325
TI  - Optimal clinical management of children receiving the ketogenic diet:
      recommendations of the International Ketogenic Diet Study Group.
AB  - The ketogenic diet (KD) is an established, effective nonpharmacologic treatment
      for intractable childhood epilepsy. The KD is provided differently throughout the
      world, with occasionally significant variations in its administration. There
      exists a need for more standardized protocols and management recommendations for
      clinical and research use. In December 2006, The Charlie Foundation commissioned
      a panel comprised of 26 pediatric epileptologists and dietitians from nine
      countries with particular expertise using the KD. This group was created in order
      to create a consensus statement regarding the clinical management of the KD.
      Subsequently endorsed by the Practice Committee of the Child Neurology Society,
      this resultant manuscript addresses issues such as patient selection, pre-KD
      counseling and evaluation, specific dietary therapy selection, implementation,
      supplementation, follow-up management, adverse event monitoring, and eventual KD
      discontinuation. This paper highlights recommendations based on best evidence,
      including areas of agreement and controversy, unanswered questions, and future
      research.

PMID- 18823326
TI  - DNA variants in coding region of EFHC1: SNPs do not associate with juvenile
      myoclonic epilepsy.
AB  - PURPOSE: Juvenile myoclonic epilepsy (JME) accounts for 3 to 12% of all
      epilepsies. In 2004, we identified a mutation-harboring Mendelian gene that
      encodes a protein with one EF-hand motif (EFHC1) in chromosome 6p12. We observed
      one doubly heterozygous and three heterozygous missense mutations in EFHC1
      segregating as an autosomal dominant gene with 21 affected members of six
      Hispanic JME families from California and Mexico. In 2006, similar and three
      novel missense mutations were reported in sporadic and familial Caucasian JME
      from Italy and Austria. In this study, we asked if coding single nucleotide
      polymorphisms (SNPs) of EFHC1 also contribute as susceptibility alleles to JME
      with complex genetics. METHODS: We screened using denaturing high-performance
      liquid chromatography (DHPLC) and then directly sequenced the 11 exons of EFHC1
      in 130 unrelated JME probands, their 352 family members, and seven exons of EFHC1
      in 400-614 ethnically matched controls. We carried out case-control association
      studies between 124 unrelated Hispanic JME probands and 552-614 ethnically
      matched controls using four SNPs, rs3804506, rs3804505, rs1266787, and
      rs17851770. We also performed family-based association on SNPs rs3804506 and
      rs3804505 in 84 complete JME families using the Family-Based Association Test
      (FBAT) program. RESULTS: We found no statistically significant differences
      between JME probands and controls in case-control association and no genetic
      transmission disequilibria in family-based association for the tested SNPs. In
      addition, we identified four new DNA variants in the coding region of EFHC1.
      CONCLUSION: The four coding SNPs, rs3804506, rs3804505, rs1266787, and
      rs17851770, of EFHC1 may not be susceptibility alleles for JME.

PMID- 18823327
TI  - Trehalose and trehalase in root nodules of Medicago truncatula and Phaseolus
      vulgaris in response to salt stress.
AB  - Trehalose (alpha-D-glucopyranosyl-1,1-alpha-D-glucopyranoside), a non-reducing
      disaccharide, has been found in a wide variety of organisms playing an important
      role as an abiotic stress protectant. Plants may come into contact with trehalose
      from exogenous sources, such as in plant-rhizobia symbiosis in which the rhizobia
      have the capacity to produce trehalose. The aim of this work is to analyse how
      trehalose and trehalase respond to salt stress in root nodules of legumes. For
      this purpose, tissue expression of Medicago truncatula trehalase gene (MTTRE1)
      and the expression of MTTRE1 under salt stress were analysed by real-time
      quantitative reverse transcription-PCR method. Trehalase activity was determined
      and trehalose was also measured by gas chromatography. In addition, trehalase
      protein occurrence in different organs and at different developmental stages in
      Phaseolus vulgaris plants has been studied. MTTRE1 expression is induced in
      nodules compared with leaves and roots, indicating a transcriptional regulation
      of trehalase in the presence of the microsymbiont. Under salt stress conditions,
      trehalase activity is downregulated at the transcriptional level, allowing
      trehalose accumulation. The results found in this study led us to conclude that
      trehalase activity is induced in root nodules of legumes by the microsymbiont and
      that under salt stress conditions; trehalase activity is downregulated at the
      transcriptional level in M. truncatula nodules. This allows trehalose
      accumulation and supports the possible role of this disaccharide as a stabilizer
      against salt stress conditions.

PMID- 18823328
TI  - Senescence progression in a single darkened cotyledon depends on the light status
      of the other cotyledon in Cucurbita pepo (zucchini) seedlings: potential
      involvement of cytokinins and cytokinin oxidase/dehydrogenase activity.
AB  - Darkness mediates different senescence-related responses depending on the
      targeting of dark treatment (whole plants or individual leaves) and on the organs
      that perceive the signal (leaves or cotyledons). As no data are available on the
      potential role of darkness to promote senescence when applied to individual
      cotyledons, we have investigated how darkness affects the progression of
      senescence in either a single or both individually darkened cotyledons of young
      10-day-old Cucurbita pepo (zucchini) seedlings. Strong acceleration of senescence
      was observed when both cotyledons were darkened as judged by the damage in their
      anatomical structure, deterioration of chloroplast ultrastructure in parallel
      with decreased photosynthetic rate and photochemical quantum efficiency of PSII.
      In addition, the endogenous levels of cytokinins (CKs) and IAA were strongly
      reduced. In a single individually darkened cotyledon, the structure and function
      of the photosynthetic apparatus as well as the contents of endogenous CKs and IAA
      were much less affected by darkness, thus suggesting inhibitory effect of the
      illuminated cotyledon on the senescence of the darkened one. Apparently, the
      effect of darkness to accelerate/delay senescence in a single darkened cotyledon
      depends on the light status of the other cotyledon from the pair. The close
      positive correlation between CK content and the activity of CK
      oxidase/dehydrogenase (CKX; EC 1.4.3.18/1.5.99.12) suggested that CKX was
      essentially involved in the mechanisms of downregulation of endogenous CK levels.
      Our results indicated that CKX-regulated CK signaling could be a possible
      regulatory mechanism controlling senescence in individually darkened cotyledons.

PMID- 18823329
TI  - Ozone-induced changes in photosynthesis and photorespiration of hybrid poplar in
      relation to the developmental stage of the leaves.
AB  - Young poplar trees (Populus tremula Michx. x Populus alba L. clone INRA 717-1B4)
      were subjected to 120 ppb of ozone for 35 days in phytotronic chambers. Treated
      trees displayed precocious leaf senescence and visible symptoms of injury (dark
      brown/black upper surface stippling) exclusively observed on fully expanded
      leaves. In these leaves, ozone reduced parameters related to photochemistry (Chl
      content and maximum rate of photosynthetic electron transport) and photosynthetic
      CO(2) fixation [net CO(2) assimilation, Rubisco (ribulose-1,5-bisphosphate
      carboxylase oxygenase) activity and maximum velocity of Rubisco for
      carboxylation]. In fully expanded leaves, the rate of photorespiration as
      estimated from Chl fluorescence was markedly impaired by the ozone treatment
      together with the activity of photorespiratory enzymes (Rubisco and glycolate
      oxidase). Immunoblot analysis revealed a decrease in the content of serine
      hydroxymethyltransferase in treated mature leaves, while the content of the H
      subunit of the glycine decarboxylase complex was not modified. Leaves in the
      early period of expansion were exempt from visible symptoms of injury and
      remained unaffected as regards all measured parameters. Leaves reaching full
      expansion under ozone exposure showed potential responses of protection
      (stimulation of mitochondrial respiration and transitory stomatal closure). Our
      data underline the major role of leaf phenology in ozone sensitivity of
      photosynthetic processes and reveal a marked ozone-induced inhibition of
      photorespiration.

PMID- 18823330
TI  - The cyclic nucleotide-gated channel, AtCNGC10, influences salt tolerance in
      Arabidopsis.
AB  - Cyclic nucleotide-gated channels (CNGCs) in the plasma membrane transport K+ and
      other cations; however, their roles in the response and adaptation of plants to
      environmental salinity are unclear. Growth, cation contents, salt tolerance and
      K+ fluxes were assessed in wild-type and two AtCNGC10 antisense lines (A2 and A3)
      of Arabidopsis thaliana (L.) Heynh. Compared with the wild-type, mature plants of
      both antisense lines had altered K+ and Na+ concentrations in shoots and were
      more sensitive to salt stress, as assessed by biomass and Chl fluorescence. The
      shoots of A2 and A3 plants contained higher Na+ concentrations and significantly
      higher Na+/K+ ratios compared with wild-type, whereas roots contained higher K+
      concentrations and lower Na+/K+ ratios. Four-day-old seedlings of both antisense
      lines exposed to salt stress had smaller Na+/K+ ratios and longer roots than the
      wild-type. Under sudden salt treatment, the Na+ efflux was higher and the K+
      efflux was smaller in the antisense lines, indicating that AtCNGC10 might
      function as a channel providing Na+ influx and K+ efflux at the root/soil
      interface. We conclude that the AtCNGC10 channel is involved in Na+ and K+
      transport during cation uptake in roots and in long-distance transport, such as
      phloem loading and/or xylem retrieval. Mature A2 and A3 plants became more salt
      sensitive than wild-type plants because of impaired photosynthesis induced by a
      higher Na+ concentration in the leaves.

PMID- 18823331
TI  - Involvement of the MP1 scaffold protein in ERK signaling regulation during
      Drosophila wing development.
AB  - Mitogen-activated protein kinase (MAPK) cascades are evolutionary conserved
      transduction pathways involved in many cellular processes. Kinase modules are
      associated with scaffold proteins that regulate signaling by providing critical
      spatial and temporal specificities. Some of these scaffold proteins have been
      shown to be conserved, both in sequence and function. In mouse, the scaffold MP1
      (MEK Partner 1) forms a signaling complex with MEK1 and ERK1. In this work, we
      focus on Drosophila MP1 (dMP1). We show that dMP1 is expressed ubiquitously
      during embryonic and larval development. By in vitro and in vivo experiments, we
      show that dMP1 is located in the cytoplasm and the nuclei, and that it interacts
      with MEK and ERK. Genetic studies with transgenic Drosophila lines allowing
      either dMP1 over-expression or dMP1 down-regulation by RNA interference highlight
      dMP1 function in the control of cell differentiation during development of the
      Drosophila wing.

PMID- 18823332
TI  - Escherichia coli tRNase Z can shut down growth probably by removing amino acids
      from aminoacyl-tRNAs.
AB  - In most organisms, tRNase Z is considered to be essential for 3' processing of
      tRNA molecules. The Escherichia coli tRNase Z gene, however, appears to be
      dispensable under normal growth conditions, and its existence remained an enigma.
      Here we intensively examined various (pre-)tRNAs for good substrates of E. coli
      tRNase Z in vitro, and found that the enzyme can remove the 3' terminal CCA
      residues from mature tRNAs regardless of their nucleotide modifications.
      Furthermore, we discovered that E. coli tRNase Z, when sufficiently expressed in
      the cell, can shut down growth probably by removing amino acids from aminoacyl
      tRNAs. We confirmed in vitro that E. coli tRNase Z exceptionally possesses the
      activity that cleaves off the 3' terminal residues charging an amino acid from an
      aminoacyl-tRNA molecule. The current data suggest that tRNase Z might help
      modulate a cell growth rate by repressing translation under some stressful
      conditions.

PMID- 18823333
TI  - Transcriptional repression of the IMD2 gene mediated by the transcriptional co
      activator Sub1.
AB  - Sub1 was originally identified as a transcriptional co-activator and later
      demonstrated to have pleiotropic functions during multiple transcription steps,
      including initiation, elongation and termination. The present study reveals a
      novel function of Sub1 as a transcription repressor in budding yeast. Sub1 does
      not activate IMP dehydrogenase 2 (IMD2) gene expression but rather represses its
      expression. First, we examined the genetic interaction of Sub1 with the
      transcription elongation factor S-II/TFIIS, which is encoded by the DST1 gene.
      Disruption of the SUB1 gene partially suppressed sensitivity to the transcription
      elongation inhibitor mycophenolate (MPA) in a dst1 gene deletion mutant. SUB1
      gene deletion increased the expression level of the IMD2 gene, which confers
      resistance to MPA, indicating that Sub1 functions to repress IMD2 gene
      expression. Sub1 located around the promoter region of the IMD2 gene. The
      upstream region of the transcription start sites was required for Sub1 to repress
      the IMD2 gene expression. These results suggest that the transcriptional co
      activator Sub1 also has a role in transcriptional repression during transcription
      initiation in vivo.

PMID- 18823334
TI  - Velocity tracking, a new and user independent method for detecting regional
      function of the left ventricle.
AB  - BACKGROUND: The use of two-dimensional echocardiography (2D echo) for detection
      of ischaemia is limited due to high user dependency. Longitudinal motion is
      sensitive for ischaemia and usable for quantitative measurement of longitudinal
      myocardial function but time consuming. Velocity tracking (VeT) is a new method
      that gives an easy three-dimensional understanding of both systolic and diastolic
      regional motion, using colour coded bull's eye presentation of longitudinal
      velocity, derived from colour coded tissue Doppler. The aim of this study was to
      test the accuracy of VeT in detecting ischaemia in non-ST-segment elevation
      myocardial infarction (NSTEMI) patients bedside. METHODS: Twenty patients with
      NSTEMI and 10 controls were included. Echocardiography was performed within 24 h
      of symptoms and prior to coronary angiography. Bull's eye plots presenting the
      peak systolic velocity (PSV) and the sum of PSV and the E-wave-velocity (PSV+E)
      were created using our developed software. VeT was compared to expert wall motion
      scoring (WMS) and bedside echo. We used the clinical conclusion based on ECG,
      angiography and clinical picture as 'gold standard'. RESULTS: Sensitivity for
      ischaemia with VeT (PSV+E) was 85% and specificity 60%. The corresponding
      sensitivities for expert WMS were 75% (specificity 40%). For regional analysis
      VeT and WMS showed comparable results with correct regional outcome in 11/20 of
      patients both superior to bedside echo. CONCLUSION: Velocity tracking is a
      promising technique that provides an easily understandable three-dimensional
      bull's eye plot for assessment of regional left ventricular longitudinal velocity
      with great potential for detection of regional dysfunction and myocardial
      ischaemia.

PMID- 18823335
TI  - Interrupter technique and pressure oscillation analysis during
      bronchoconstriction in children.
AB  - The use of interrupter resistance (R(int)) is a feasible method of measuring
      bronchodilator responsiveness and bronchial hyperresponsiveness in preschool
      children. It has been suggested that analysis of recorded oscillations of the
      mouth pressure may provide additional indices of changes in airway mechanics. The
      aim of our study was to determine whether amplitude or damping properties of
      oscillations were more sensitive than R(int) in describing changes during
      bronchoconstriction. Data from 44 children (24 boys) who completed tripling dose
      methacholine (Mch) challenge were analysed. The median (range) age of children
      was 4.9 (3.1-6.1 years). In addition to baseline and maximal R(int) after Mch
      [mean (SD) were 0.92 (0.19) and 1.44 (0.35) kPa l(-1) s, respectively], obtained
      from a commercial device we analysed the following parameters: difference between
      the first maximum and minimum (A(MxMn)), maximum instantaneous amplitude
      (A(inst)), amplitudes of fitted mathematical model and the dominant frequency,
      sum of frequency component amplitudes, two damping factors and frequency. All
      amplitude parameters changed significantly after Mch. For comparison of the
      decrease in amplitudes and increase in R(int) we additionally used reciprocals of
      amplitudes. Using the sensitivity index (SI) i.e. the change after intervention
      divided by the baseline SD, 1/A(inst) and 1/A(MxMn) were the most sensitive
      indices to describe the change (with median SI of 6.29 and 6.28, respectively).
      R(int) had a median SI of 5.13. Frequency and damping factors were less
      sensitive, with median SI values <1. These findings suggest that oscillation
      amplitude analysis implemented in the software of commercial devices could have
      further applications in assessing respiratory mechanics.

PMID- 18823336
TI  - The effect of glibenclamide on acetylcholine and sodium nitroprusside induced
      vasodilatation in human cutaneous microcirculation.
AB  - OBJECTIVE: K(ATP) channels have an important regulatory role in resting vascular
      tone and during hypoxia. Their role in endothelium dependent and independent
      vasodilatation in human skin microcirculation is less known. METHODS: We
      monitored the laser-Doppler (LD) response in 14 healthy male volunteers on the
      skin of the forearm. In the case of endothelium dependent vasodilatation
      [acetylcholine (ACh) induced], a saline solution (used as control) or a solution
      of glibenclamide (K(ATP) channel blocker) were randomly injected each into a
      distinct measurement site on different forearms followed by the iontophoresis of
      ACh. In the case of endothelium dependent vasodilatation with the inhibition of
      prostaglandin production, diclofenac (cyclooxygenase inhibitor) or the
      combination of diclofenac and glibenclamide were randomly injected each into a
      distinct measurement site on different forearms followed by the iontophoresis of
      ACh. In the case of endothelium independent vasodilatation [sodium nitroprusside
      (SNP) induced], a saline solution or glibenclamide were randomly injected each
      into a distinct measurement site on different forearms, iontophoresis of SNP
      followed. RESULTS: Glibenclamide alone, diclofenac alone or the combination of
      glibenclamide and diclofenac reduced the LD flux values during rest and after ACh
      application (P<0.05). The reduction of LD flux in ACh mediated vasodilatation was
      greatest when using the combination of glibenclamide and diclofenac. In the case
      of SNP application, there was also a significantly lower LD flux rise for
      glibenclamide in comparison with the saline solution (P<0.05). CONCLUSIONS:
      K(ATP) channels play an important role in human cutaneous vasodilatation induced
      by ACh and SNP.

PMID- 18823337
TI  - Power Doppler sonography in the diagnosis of hemophilic synovitis--a promising
      tool.
AB  - BACKGROUND: Recurrent hemarthroses in hemophilia results in synovitis and joint
      arthropathy. Primary prophylaxis when universally instituted at current doses can
      prevent joint deterioration but is expensive. Alternatively, the selective
      implementation of prophylaxis would require a more sensitive tool for detecting
      synovitis than possible with clinical surveillance or plain radiographs. Magnetic
      resonance imaging (MRI) is such a tool and is utilized for the evaluation of
      hemophilic joint disease (HJD). However, it is expensive, and requires sedation
      in younger children precluding its utility for monitoring of synovitis.
      Ultrasonography (USG) with power Doppler (USG-PDS) has been utilized to detect
      and quantitate synovial vascularity in other arthritides and could provide an
      equally effective but less costly tool for HJD, particularly in children who
      would not require sedation. OBJECTIVES: To determine whether USG-PDS is
      comparable to MRI in the evaluation of hemophilic synovitis. PATIENTS: A
      prospective cohort of 31 subjects including 33 joints (knees, elbows, ankles)
      underwent dynamic contrast enhanced (DCE)-MRI and USG-PDS. RESULTS: USG-PDS
      measurements of synovial thickness(r = 0.70, P < 0.0001) and synovial vascularity
      (r = 0.73, P < 0.0001) correlated strongly with those obtained with DCE-MRI. A
      cutoff of PDS intensity of 1.3 decibels (dB) per mm(2) was found to yield a
      sensitivity of 100% and a specificity of 94.1% in 17 joints with/without a
      history of hemarthroses. Pettersson radiographic scores correlated significantly
      with synovial thickness in adults but not children. CONCLUSIONS: Our data suggest
      that USG-PDS may be an inexpensive and easily implemented imaging tool for
      detecting hemophilic synovitis and could be useful in tailoring effective
      prophylaxis.

PMID- 18823338
TI  - Diverse Mpl expression pattern among pedigrees with inherited thrombocytopenia:
      potential diagnostic and therapeutic implications.

PMID- 18823339
TI  - Reduced factor VII and factor VIII levels and prolonged thrombin-generation times
      during a healthy diet in middle-aged women with mild to moderate cardiovascular
      disease risk.
AB  - BACKGROUND: No experimental study has investigated the effect of whole-diet
      therapies on a wide range of hemostatic parameters, and their relationship with
      metabolic and inflammatory markers. Such information was sought in middle-aged
      women with moderate cardiovascular disease (CVD) risk subjected to an integrated
      healthy diet. METHODS: Forty-nine premenopausal women were screened for C
      reactive protein levels > or =1 mg L(-1) and at least one additional CVD risk
      factor. Sixteen women (age: 43-54 years) were selected and received a 12-week
      diet (four phases) integrating National Cholesterol Education Program-Adult
      Treatment Panel-III recommendations with components of a Mediterranean-style
      diet. RESULTS: We observed a reduction in body mass index (BMI) (P = 0.001),
      waist circumference (P = 0.005), total (P = 0.011) and low-density lipoprotein
      (LDL) cholesterol levels (P = 0.035). Antigen levels of coagulation factor (F)VII
      (P = 0.003) and FVIII (P = 0.005) were clearly reduced by dietary intervention,
      which also appeared to decrease circulating tissue factor but not fibrinogen and
      von Willebrand factor (VWF) antigen levels. Levels of FVIII and tumor necrosis
      factor-alpha, among the inflammation markers, showed the highest correlation,
      particularly before the intervention (r = 0.55, P = 0.032). Only this cytokine
      influenced FVIII variation over time, thus highlighting new relations between
      coagulation and cellular components of inflammation. The functional effect of
      diet on coagulation was indicated by markedly prolonged thrombin generation
      initiation and propagation times (lag time, P = 0.002; time to peak, P = 0.005).
      CONCLUSIONS: The changes observed in coagulation initiation and amplification
      phases, body composition and lipid profile could translate into a remarkable
      decrease in the risk for cardiovascular disease. Our observations suggest novel
      relationships between coagulation and inflammatory components.

PMID- 18823340
TI  - Dual antiplatelet therapy unmasks distinct platelet reactivity in patients with
      coronary artery disease.
AB  - BACKGROUND: Platelet-induced thrombosis is a major risk factor for recurrent
      ischemic events, although platelet function in patients with cardiovascular
      disease taking aspirin and clopidogrel is very poorly characterized. The aim of
      this study was to assess platelet reactivity in patients with cardiovascular
      disease taking aspirin and clopidogrel. METHODS: We developed a rapid assay to
      measure platelet aggregation in response to arachidonic acid, collagen, adenosine
      diphosphate (ADP), epinephrine and thrombin receptor activating peptide (TRAP) in
      80 healthy volunteers. We then recruited 200 consecutive patients from outpatient
      clinics and the cardiac catheterization laboratory and tested platelet function.
      Platelet aggregation induced by epinephrine is a marker of global platelet
      reactivity. We tested platelet function in 146 patients compliant with
      antiplatelet therapy. Platelet aggregation to epinephrine was divided into
      quartiles. The platelet response to the other agonists was analysed based on the
      response to epinephrine. RESULTS: Platelet reactivity increased significantly
      across the quartiles in response to epinephrine in healthy volunteers and
      patients (P < 0.0001). A significant increase in response across quartiles was
      seen with all agonists in healthy volunteers (P < 0.001). In contrast, a
      significant increase in response across quartiles was only seen with ADP in
      patients (P < 0.0001). Hypertension, smoking and diabetes were significantly
      associated with increasing platelet reactivity to epinephrine (P < 0.05).
      CONCLUSION: This study shows that platelet response differs between healthy
      volunteers and patients on dual antiplatelet therapy. In patients with
      cardiovascular disease, dual antiplatelet therapy unmasks a distinct type of
      platelet reactivity in response to epinephrine and ADP but not other agonists.

PMID- 18823341
TI  - Building-related symptoms and stress indicators.
AB  - This study aims to study physiological stress indicators in relation to
      prevalence of building-related symptoms (BRS) among teachers employed in three
      selected schools in Copenhagen. Three hypotheses were studied: (i) Perceived
      psychosocial work environment was associated with BRS; (ii) Perceived
      psychosocial work environment (job strain) was associated with physiological
      strain; (iii) BRS was associated with physiological strain. We found a tendency
      among women of an association between job strain and being BRS positive. Also an
      association between job strain and physiological strain was observed among women.
      Being BRS positive was not associated with single physiological stress indicators
      with the exception of a higher level free testosterone in serum among BRS
      positive women. PRACTICAL IMPLICATIONS: Including physiological stress indicators
      may be a supplementary measure to questionnaires when studying the association
      between the psychosocial work environment and building-related symptoms (BRS). In
      this study, job strain was associated with physiological strain among women.
      Being BRS positive was not associated with single physiological stress indicators
      with the exception of a higher level free testosterone in serum among BRS
      positive women. This study should be regarded as a preliminary study because of
      its small number of participants.

PMID- 18823342
TI  - Indoor air disinfection using a polyester supported TiO2 photo-reactor.
AB  - Among the decontamination methods applicable to indoor air, heterogeneous
      photocatalysis has received increasing attention in recent years. This
      decontamination method is based on the UV irradiation of a solid catalyst,
      normally TiO2, aiming at the generation of highly reactive hydroxyl radicals. In
      this work, a novel way to prepare the photocatalyst was used, incorporating pure
      P-25 TiO2 (Degussa) into polyester orthophthalic polymer. The film was coated
      onto the walls of a PVC reactor with a concentric 30 W germicidal lamp (254 nm).
      The efficiency of this prototype was evaluated against fungi and bacteria
      elimination in a 67 m3 confined room. The system was very efficient for bacteria
      reduction, decreasing the bacterial count to below the detection limit (1
      CFU/plate during 30-min sampling) after 2 h of operation at 195 l/min. For fungi,
      the gas-phase reactor showed to be less efficient and silver doping of the
      catalyst showed no increase in biocide activity. PRACTICAL IMPLICATIONS: The use
      of a photocatalytic reactor based on TiO2 incorporated onto polyester
      orthophtalic polymer has been tested at 195 l/min, showing good performance in
      the air disinfection of a 67 m3 room.

PMID- 18823343
TI  - Characterization of indoor air quality in primary schools in Antwerp, Belgium.
AB  - The indoor air quality of 27 primary schools located in the city centre and
      suburbs of Antwerp, Belgium, was assessed. The primary aim was to obtain
      correlations between the various pollutant levels. Indoor:outdoor ratios and the
      building and classroom characteristics of each school were investigated. This
      paper presents results on indoor and local outdoor PM2.5 mass concentrations, its
      elemental composition in terms of K, Ca, Ti, V, Cr, Mn, Fe, Ni, Cu, Zn, Br, Pb,
      Al, Si, S, and Cl, and its black smoke content. In addition, indoor and local
      outdoor levels of the gases NO2, SO2, O3, and BTEX (benzene, toluene, ethyl
      benzene, and xylene isomers) were determined. Black smoke, NO2, SO2 and O3,
      occurred at indoor:outdoor ratios below unity, indicating their significant
      outdoor sources. No linear correlation was established between indoor and outdoor
      levels for PM2.5 mass concentrations and BTEX; their indoor:outdoor ratios
      exceeded unity except for benzene. Classroom PM2.5 occurred with a different
      elemental composition than local outdoor PM2.5. The re-suspension of dust because
      of room occupation is probably the main contributor for the I/O ratios higher
      than 1 reported for elements typically constituting dust particles. Finally,
      increased benzene concentrations were reported for classrooms located at the
      lower levels. PRACTICAL IMPLICATIONS: The elevated indoor PM2.5, and BTEX
      concentrations in primary school classrooms, exceeding the ambient
      concentrations, raise concerns about possible adverse health effects on
      susceptible children. This is aggravated by the presence of carpets and in the
      case of classrooms at lower levels. Analysis of PM2.5's elemental composition
      indicated a considerable contribution of soil dust to indoor PM2.5 mass. In order
      to set adequate threshold values and guidelines, detailed information on the
      health impact of specific PM2.5 composites is needed. The results suggest that
      local outdoor air concentrations measurements do not provide an accurate
      estimation of children's personal exposures to the identified air pollutants
      inside classrooms.

PMID- 18823344
TI  - Effects of treatment on soluble tumour necrosis factor receptor type 1 and 2 in
      chronic periodontitis.
AB  - AIM: We reported that soluble tumour necrosis factor receptor type 2
      (sTNFR2)/type 1 (sTNFR1) ratios in gingival crevicular fluid (GCF) decreased as
      the severity of chronic periodontitis (CP) increased. This study investigated the
      effects of the periodontal treatment on TNF-alpha, sTNFR1 and R2 in GCF and serum
      of CP patients. MATERIAL AND METHODS: Thirty-five serum and 90 GCF samples were
      obtained from 35 CP patients (23 non-smokers and 12 smokers) at baseline and
      after treatment. The levels of TNF-alpha, sTNFR1 and R2 in serum and GCF were
      quantified by enzyme-linked immunosorbant assay. RESULTS: No significant
      differences were found in the serum levels of TNF-alpha, sTNFR1 and R2 and the
      ratio of sTNFR2/R1 between baseline and after treatment. After treatment, sTNFR1
      and R2 levels in GCF of non-smokers and smokers were significantly decreased
      compared with baseline. However, the sTNFR2/R1 ratio was significantly increased
      (non-smoker: 0.56+/-0.03-0.84+/-0.03, p<0.0001; smoker: 0.59+/-0.06-0.85+/-0.04,
      p=0.0019). There were no significant differences between non-smoking and smoking
      CP groups in serum and GCF. CONCLUSION: The ratio of sTNFR2/R1 in GCF
      significantly increased after treatment, and could be related to the clinical
      state of CP.

PMID- 18823345
TI  - Adolescents' sense of coherence and smoking as longitudinal predictors of self
      reported gingivitis.
AB  - OBJECTIVE: This study sought to determine the influence of sense of coherence
      (SOC), a personal stress-coping resource, and smoking on the self-reported
      gingival health of a cohort of rural black South African adolescents. METHODS:
      This 18-month study involved a three-wave survey of a representative sample of
      eighth graders from 11 randomly selected high schools in the Limpopo province,
      South Africa (n=970). Using a generalized estimating equation model, we examined
      the correlates of recent gingivitis, defined as self-reporting frequent gingival
      bleeding (GB). Explanatory variables included baseline socio-economic status,
      age, gender, plaque levels, toothbrushing frequency, tobacco use status and SOC
      levels. RESULTS: Among our sample, 74.6% reported experiencing gingivitis at some
      point during follow-up, while 41.9% reported frequent GB at the last survey.
      Factors that were positively associated with recent gingivitis include living in
      poor households [odds ratio (OR)=1.49; p<0.01], having higher plaque levels
      (OR=1.18; p=0.04) and smoking regularly (OR=1.57; p=0.04). Self-reporting
      gingivitis was negatively associated with being female (OR=0.76; p=0.02) and
      having a higher SOC (OR=0.96; p<0.001). CONCLUSIONS: Adolescent smoking and SOC
      levels are independent predictors of self-reported gingivitis. Therefore, in
      addition to plaque control, smoking prevention and the teaching of stress-coping
      skills may be important interventions for promoting adolescents' gingival health.

PMID- 18823346
TI  - Mannose-binding lectin gene polymorphisms in relation to periodontitis.
AB  - AIM: To investigate the correlation of six functional polymorphisms in the MBL
      gene with MBL plasma levels in relation to periodontitis. MATERIAL AND METHODS: A
      total of 92 periodontitis patients and 70 controls, all of Caucasian origin, were
      included. Patients and controls were genotyped for the L/H, X/Y, P/Q, A/D, A/B
      and A/C polymorphisms. Distributions of genotypes, rate of allele carriage and
      allele frequencies were compared between patients and controls. Patients and
      controls were subdivided in groups of genotypes. Plasma MBL levels were compared
      between different genotype groups. RESULTS: On the basis of genotyping, three
      phenotypes with regard to mannose-binding lectin (MBL) production were
      distinguished: high-producers, low-producers and deficient subjects. No
      differences in the genotype frequencies were observed between patients and
      controls. Within patients and controls, subjects with the high-producing
      genotypes had significantly higher MBL plasma levels than low-producers and
      deficient subjects (p<0.001). Plasma MBL was higher in low-producer patients
      compared with low-producer controls (p(adjusted)=0.021). CONCLUSION: No
      association could be observed between MBL gene polymorphisms and susceptibility
      to periodontitis in Caucasians. However, now that genotyping could distinguish
      the low producing and deficient subjects from the high-producers, it was
      observed, for the first time, that MBL acts as a weak acute-phase protein in
      periodontitis.

PMID- 18823347
TI  - Lubricating gel as an aid to coat the passage of 6/0 polyglactin 910 (Vicryl
      Rapide).

PMID- 18823348
TI  - Surgical intervention for a penoscrotal ulcer: a note of caution.

PMID- 18823349
TI  - Giant genital seborrheic keratosis or Buschke Lowenstein tumor?

PMID- 18823350
TI  - Umbilical pyogenic granuloma associated with occult omphalith.

PMID- 18823351
TI  - Basal cell and squamous cell carcinoma occurring within a field of multiple
      tumors of the follicular infundibulum.

PMID- 18823352
TI  - Tripier flap for medial lower eyelid reconstruction.

PMID- 18823353
TI  - Modified single-sling myocutaneous island pedicle flap: series of 61
      reconstructions.
AB  - BACKGROUND: Bilevel undermining above and below the transverse nasalis muscle in
      the construction of a myocutaneous island pedicle flap produces a bilateral or
      unilateral muscular sling with exceptional vascular supply for reconstruction of
      defects on the distal nose. We present further modification of the single-sling
      myocutaneous island pedicle flap that expands its application to a wide variety
      of nasal defects and further defines its usefulness in nasal reconstruction.
      METHODS: A series of 61 consecutive myocutaneous island pedicle flap
      reconstructions performed after Mohs surgery between March 2005 and July 2006 are
      presented. Flap modifications are presented, and advantages and limitations are
      discussed. RESULTS: Flap modifications introduce additional reach and rotational
      mobility to the flap that permit extension of the flap to defects on the nasal
      tip and distal ala. CONCLUSION: Modifications of the bilevel approach to the
      single-sling nasalis myocutaneous island pedicle flap further define its
      practicality in nasal reconstruction and expand its application to a variety of
      nasal defects.

PMID- 18823354
TI  - Saccharomyces kluyveri as a model organism to study pyrimidine degradation.
AB  - The yeast Saccharomyces kluyveri (Lachancea kluyveri), a far relative of
      Saccharomyces cerevisiae, is not a widely studied organism in the laboratory.
      However, significant contributions to the understanding of nucleic acid
      precursors degradation in eukaryotes have been made using this model organism.
      Here we review eukaryotic pyrimidine degradation with emphasis on the
      contributions made with S. kluyveri and how this increases our understanding of
      human disease. Additionally, we discuss the possibilities and limitations of this
      nonconventional yeast as a laboratory organism.

PMID- 18823355
TI  - Health status, symptoms and health counselling among middle-aged men: comparison
      of men at low and high risk.
AB  - AIM: To assess the levels of health indicators, health behaviour and health
      counselling among men at low and high risk for adverse health outcomes. METHODS:
      A total of 273 middle-aged men, 145 at low and 128 at high risk for adverse
      health outcomes, were studied. Two- and three-way tables with chi-squared tests
      were performed to identify differences between the groups. A step-wise logistic
      regression model was used to analyse symptoms and complaints associated with the
      likelihood of perceived health. RESULTS: One-half of the low-risk men were
      overweight, of whom 8% were obese. Forty per cent of the low-risk men smoked
      cigarettes and one-fifth used alcohol excessively. Headache, chest and back pain,
      stress, and insomnia occurred frequently (range: 20-38%) and were highly
      correlated with depression. Joint pain (p = 0.012) in the low-risk men and
      sciatica (p = 0.047) in the high-risk men were the only statistically significant
      differences related to normal weight vs. overweight status. There was a greater
      than sixfold odds of average/poor health among low-risk men who were depressed
      than in those who were not depressed men. Only a small percentage of the low-risk
      men had received counselling from professionals for different health issues,
      including weight control and smoking cessation; the corresponding percentages
      were somewhat higher when given by family members. CONCLUSIONS: A real need for
      better counselling was found among middle-aged men identified with obesity and
      risky behaviours. Public health nurses and other health workers should be aware
      of the differences between men at low and high risk. Men had different health
      experiences and lifestyles in these groups. More research is needed to determine
      the most efficient counselling strategies among men.

PMID- 18823356
TI  - Challenges in the diagnosis and management of Nocardia infections in lung
      transplant recipients.
AB  - BACKGROUND: Nocardia infection occurs in 2.1-3.5% of lung transplant recipients,
      and may involve cavitary nodular pulmonary lesions, soft tissue infection, or
      other sites of dissemination. Nocardiosis can pose challenging clinical problems
      in the areas of diagnosis and treatment. Diagnostic delays may occur, and adverse
      reactions to therapy are common. This study reviews clinical and epidemiological
      aspects of nocardiosis in lung transplant recipients, with special attention to
      pitfalls in management. Clinicians should be alert for these possibilities in
      order to institute prompt therapy and to achieve successful outcomes. METHODS: A
      retrospective cohort study was conducted of 577 lung transplant recipients from
      January 1991 to May 2007. Demographics, reason for transplant, recent rejection,
      time from transplantation, site of infection, hypogammaglobulinemia, and/or
      neutropenia shortly before onset, Pneumocystis jiroveci prophylaxis, Nocardia
      species, radiographic findings, extrapulmonary lesions, nature and duration of
      treatment, adverse reactions, and outcomes were recorded. RESULT: Nocardia
      infection occurred in 1.9% (11/577). Mean onset was 14.3 months after transplant
      (range 1.5-39 months). N. asteroides was isolated in 55% (6/11). Emphysema was
      the most common reason for transplant (7/11, 64%). Six patients were receiving
      trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis at the time of diagnosis.
      Three patients had immune globulin G levels <400 mg/dL and 2 were neutropenic in
      the 3 months preceding diagnosis. Diagnosis was made by bronchoalveolar lavage
      (55%), skin abscess culture (18%), open lung biopsy (9%), pleural fluid (9%), and
      sputum culture (9%). Definitive diagnosis required a median of 9 days and a mean
      of 13.6 days (range 3-35 days) from the time of diagnostic sampling. Soft tissue
      lesions occurred in 3 and central nervous system involvement in 1 patient.
      Adverse reactions to therapy occurred in 9/10 (90%) of patients for whom
      information was available. Nocardia-related mortality occurred in 2/11 patients
      (18%). CONCLUSIONS: Nocardiosis occurred in 1.9% of lung transplant recipients
      and was associated with a mean of nearly 2 weeks to diagnosis and frequent
      adverse effects on therapy. TMP-SMX prophylaxis on a thrice weekly basis did not
      prevent all episodes of nocardiosis. Despite utilization of protocol
      bronchoscopies with cultures for Nocardia, this organism remains a source of
      clinical complexity in the lung transplant population.

PMID- 18823357
TI  - Sublingual immunotherapy in children: more optimism today.

PMID- 18823358
TI  - A multicenter survey of childhood asthma in Turkey. II: Utilization of asthma
      drugs, control levels and their determinants.
AB  - Many surveys worldwide have consistently demonstrated a low level of asthma
      control and under-utilization of preventive asthma drugs. However, these studies
      have been frequently criticized for using population-based samples, which include
      many patients with no or irregular follow-ups. Our aim, in this study, was to
      define the extent of asthma drug utilization, control levels, and their
      determinants among children with asthma attending to pediatric asthma centers in
      Turkey. Asthmatic children (age range: 6-18 yr) with at least 1-yr follow-up seen
      at 12 asthma outpatient clinics during a 1-month period with scheduled or
      unscheduled visits were included and were surveyed with a questionnaire-guided
      interview. Files from the previous year were evaluated retrospectively to
      document control levels and their determinants. From 618 children allocated, most
      were mild asthmatics (85.6%). Almost 30% and 15% of children reported current use
      of emergency service and hospitalization, respectively; and 51.4% and 53.1% of
      children with persistent and intermittent disease, respectively, were on daily
      preventive therapy, including inhaled corticosteroids. Disease severity [odds
      ratio: 12.6 (95% confidence intervals: 5.3-29.8)], hospitalization within the
      last year [3.4 (1.4-8.2)], no use of inhaled steroids [2.9 (1.1- 7.3)], and
      female gender [2.3 (1.1-5.4)] were major predictors of poor asthma control as
      defined by their physicians. In this national pediatric asthma study, we found a
      low level of disease control and discrepancies between preventive drug usage and
      disease severity, which shows that the expectations of guidelines have not been
      met even in facilitated centers, thus indicating the need to revise the severity
      based approach of asthma guidelines. Efforts to implement the control-based
      approach of new guidelines (Global Initiative for Asthma 2006) would be
      worthwhile.

PMID- 18823359
TI  - Gender differences in the association of overweight and asthma morbidity among
      urban adolescents with asthma.
AB  - Asthma and obesity disproportionately affect US African-American youth. Among
      youth with asthma, obesity has been associated with poor control. The impact of
      gender on this association is unclear. We examined these relationships in a
      sample of urban, African-American adolescents with asthma. Questionnaires were
      used to identify high school students with asthma, and to examine the association
      of body mass index (BMI) to asthma morbidity, by gender. Of 5967 students
      completing questionnaires, 599 (10%) met criteria for asthma and 507 had data
      sufficient for inclusion in further analyses (46% male, mean age = 15.1 yr).
      Univariately, BMI > 85th percentile was significantly related only to reported
      emergency department visits (ED) and school days missed for any reason, Odds
      Ratio (95%Confidence Interval) = 1.7(1.1-2.7), p = 0.01 and 1.8(1.1-3.0), p =
      0.01, respectively. A significant gender-BMI interaction (p < 0.05) was observed
      in multivariate models for ED visits, hospitalizations and school days missed for
      asthma. In gender-specific models, adjusted Risk Ratios for BMI > 85th and ED
      visits, hospitalizations, and school days missed because of asthma were 1.7(0.9
      3.2), 6.6(3.1-14.6) and 3.6(1.8-7.2) in males. These associations were not
      observed in females. Gender modifies the association between BMI and asthma
      related morbidity among adolescents with asthma. Results have implications for
      clinical management as well as future research.

PMID- 18823360
TI  - Ictal headache and visual sensitivity.
AB  - Migrainous headache is reported by patients with photosensitive epilepsy, whereas
      their relatives complain more often about headache than the relatives of patients
      with other types of epilepsy. We therefore investigated whether headache itself
      could be an epileptic symptom related to photosensitivity. Four probands with
      headache and photosensitive epilepsy were selected. Their first-degree family
      members were studied using video-EEG with extensive intermittent photic
      stimulation and pattern stimulation. Nine of the 12 subjects (10 female and two
      male, mean age 30 years, range 14-46 years) proved to be photosensitive with
      either focal (n = 5) or generalized (n = 4) epileptiform discharges. In two
      subjects an ictal recording of headache occurred after visual stimulation. We
      found evidence that, in specific patients, headache could be an ictal sign of
      epilepsy. Photic stimulation during EEG recording can contribute to correct
      diagnosis and lead to the best care and management of the patient.

PMID- 18823361
TI  - Headache classification by history has only limited predictive value for headache
      episodes treated in controlled trials with OTC analgesics.
AB  - We investigated the consistency between the headache diagnosis based on medical
      history and three treated headache episodes diagnosed based on a diary. In a
      randomized double-blind study including individuals with either migraine or
      tension-type headache (TTH) we showed significant superiority of the fixed
      combination of acetylsalicylic acid + paracetamol + caffeine over the combination
      without caffeine, the single preparations, and placebo in the treatment of
      headache. A neurologist performed a classification of the usual headache episodes
      and each of the three treated ones in a blinded fashion based on a structured
      questionnaire. This was done for the 1734 patients included in the efficacy
      analysis who usually treated their episodic TTH or migraine attacks with non
      prescription analgesics. The overall percentage of patients with migraine and TTH
      remained relatively stable. The treated headache episodes were between 75 and 77%
      migraine, 18-20% were TTH and 5-7% could not be classified. We observed some
      shift in headache type within patients from prior history and in treated attacks.
      In 60% of patients all three treated episodes were of the type initially
      diagnosed by the neurologist by history (56% migraine and 4% episodic TTH). Of
      those with an initial diagnosis of migraine, 24% had at least one attack meeting
      criteria for TTH. Of patients with an initial diagnosis of TTH, 54% had at least
      one attack meeting the diagnostic criteria for migraine. Our results demonstrate
      that an initial headache diagnosis does not accurately predict the headache type
      treated in a randomized trial. Symptom features of treated headaches should be
      captured to ensure that the attack is of the type targeted by the clinical trial.
      The International Headache Society Guidelines for controlled clinical trials
      should be updated accordingly.

PMID- 18823362
TI  - Prevalence of primary headaches and cranial neuralgias in men and women aged 55
      94 years (Bruneck Study).
AB  - The aim of the current study was to estimate the prevalence of all primary
      headaches and cranial neuralgias in the general community. As part of the
      population-based Bruneck Study, 574 men and women aged 55-94 years underwent
      extensive neurological and laboratory examinations involving a standardized
      headache interview. In the Bruneck Study population the lifetime prevalence of
      all primary headaches combined and of cranial neuralgias was 51.7 and 1.6%,
      respectively. Tension-type headache (40.9%) and migraine (19.3%) emerged as the
      most common types of headache. In men and women aged 55-94 years the 1-year
      prevalence of primary headaches was high at 40.5%. In this age range headaches
      caused significant impairment of health-related quality of life. The Bruneck
      Study has confirmed the high lifetime prevalence of primary headaches and cranial
      neuralgias in the general population and provided first valid prevalence data for
      all primary headaches based on International Classification of Headache
      Disorders, 2nd edition criteria.

PMID- 18823363
TI  - Management of medication overuse headache: 1-year randomized multicentre open
      label trial.
AB  - It is a general belief that patients with medication overuse headache (MOH) need
      withdrawal of acute headache medication before they respond to prophylactic
      medication. In this 1-year open-labelled, multicentre study intention-to-treat
      analyses were performed on 56 patients with MOH. These were randomly assigned to
      receive prophylactic treatment from the start without detoxification, undergo a
      standard out-patient detoxification programme without prophylactic treatment from
      the start, or no specific treatment (5-month follow-up). The primary outcome
      measure, change in headache days per month, did not differ significantly between
      groups. However, the prophylaxis group had the greatest decrease in headache days
      compared with baseline, and also a significantly more pronounced reduction in
      total headache index (headache days/month x headache intensity x headache hours)
      at months 3 (P = 0.003) and 12 (P = 0.017) compared with the withdrawal group. At
      month 12, 53% of patients in the prophylaxis group had > or = 50% reduction in
      monthly headache days compared with 25% in the withdrawal group (P = 0.081).
      Early introduction of preventive treatment without a previous detoxification
      programme reduced total headache suffering more effectively compared with abrupt
      withdrawal. (ClinicalTrials.gov number, NCT00159588).

PMID- 18823364
TI  - Medication overuse headache and chronic migraine in a specialized headache
      centre: field-testing proposed new appendix criteria.
AB  - The classification subcommittee of the International Headache Society (IHS) has
      recently suggested revised criteria for medication overuse headache (MOH) and
      chronic migraine (CM). We field tested these revised criteria by applying them to
      the headache population at the Danish Headache Centre and compared the results
      with those using the current criteria. For CM we also tested two alternative
      criteria, one requiring > or = 4 migraine days/month and > or = 15 headache
      days/month, the second requiring > or = 15 headache days/month and > or = 50%
      migraine days. We included 969 patients with migraine or tension-type headache
      (TTH) among 1326 patients treated and dismissed in a 2-year period. Two hundred
      and eighty-five patients (30%) had TTH, 265 (27%) had migraine and 419 (43%) had
      mixed migraine and TTH. The current criteria for MOH classified 86 patients (9%)
      as MOH, 98 (10%) as probable MOH and 785 (81%) as not having MOH after a 2-month
      drug-free period. Using the appendix criteria, 284 patients (29%) were now
      classified as MOH, no patients as probable MOH and 685 (71%) as not having MOH.
      For CM only 16 patients (3%) fulfilled the current diagnostic criteria. This
      increased to 42 patients (7%) when we applied the appendix criteria. Using the
      less restrictive criteria of > or = 4 migraine days and > or = 15 headache days,
      88 patients (14%) had CM, whereas the more restrictive criteria of > or = 15
      headache days and > or = 50% migraine days resulted in 24 patients (4%) with CM.
      Our data suggest that the IHS has succeeded in choosing new criteria for CM which
      are neither too strict, nor too loose. For MOH, a shift to the appendix criteria
      will increase the number of MOH patients, but take into account the possibility
      of permanent changes in pain perception due to medication overuse and the
      possibility of a renewed effect of prophylactic drugs due to medication
      withdrawal. We therefore recommend the implementation of the appendix criteria
      for both MOH and CM into the main body of the International Classification of
      Headache Disorders.

PMID- 18823365
TI  - Correlation between abnormal brain excitability and emotional symptomatology in
      paediatric migraine.
AB  - We investigated a possible correlation between brain excitability in children
      with migraine and tension-type headache (TTH) and their behavioural
      symptomatology, assessed by using the Child Behaviour Checklist (CBCL). The
      mismatch negativity (MMN) and P300 response were recorded in three successive
      blocks to test the amplitude reduction of each response from the first to the
      third block (habituation). MMN and P300 habituation was significantly lower in
      migraineurs and TTH children than in control subjects (two-way ANOVA: P < 0.05).
      In migraineurs, but not in TTH patients, significant positive correlations
      between the P300 habituation deficit and the CBCL scores were found (P < 0.05),
      meaning that the migraineurs with the most reduced habituation showed also the
      worst behavioural symptomatology. To the best of our knowledge, this is the first
      study showing a correlation between neurophysiological abnormality and emotional
      symptomatology in migraine, suggesting a role of the latter in producing the
      migrainous phenotype.

PMID- 18823366
TI  - Activation and membrane binding of retinal protein kinase Balpha/Akt1 is
      regulated through light-dependent generation of phosphoinositides.
AB  - Akt is a phospholipid-binding protein and the downstream effector of the
      phosphoinositide 3-kinase (PI3K) pathway. Akt has three isoforms: Akt1, Akt2, and
      Akt3. All of these isoforms are expressed in rod photoreceptor cells, but the
      individual functions of each isoform are not known. In this study, we found that
      light induces the activation of Akt1. The membrane binding of Akt1 to rod outer
      segments (ROS) is insulin receptor (IR)/PI3K-dependent as demonstrated by reduced
      binding of Akt1 to ROS membranes of photoreceptor-specific IR knockout mice.
      Membrane binding of Akt1 is mediated through its Pleckstrin homology (PH) domain.
      To determine whether binding of the PH domain of Akt1 to photoreceptor membranes
      is regulated by light, various green fluorescent protein (GFP)/Akt1-PH domain
      fusion proteins were expressed in rod photoreceptors of transgenic Xenopus laevis
      under the control of the Xenopus opsin promoter. The R25C mutant PH domain of
      Akt1, which does not bind phosphoinositides, failed to associate with plasma
      membranes in a light-dependent manner. This study suggests that light-dependent
      generation of phosphoinositides regulates the activation and membrane binding of
      Akt1 in vivo. Our results also suggest that actin cytoskeletal organization may
      be regulated through light-dependent generation of phosphoinositides.

PMID- 18823367
TI  - The blood-brain barrier significantly limits eflornithine entry into Trypanosoma
      brucei brucei infected mouse brain.
AB  - Drugs to treat African trypanosomiasis are toxic, expensive and subject to
      parasite resistance. New drugs are urgently being sought. Although the existing
      drug, eflornithine, is assumed to reach the brain in high concentrations, little
      is known about how it crosses the healthy and infected blood-brain barrier. This
      information is essential for the design of drug combinations and new drugs. This
      study used novel combinations of animal models to address these omissions.
      Eflornithine crossed the healthy blood-CNS interfaces poorly, but this could be
      improved by co-administering suramin, but not nifurtimox, pentamidine or
      melarsoprol. Work using a murine model of sleeping sickness demonstrated that
      Trypanosoma brucei brucei crossed the blood-CNS interfaces, which remained
      functional, early in the course of infection. Concentrations of brain parasites
      increased during the infection and this resulted in detectable blood-brain
      barrier, but not choroid plexus, dysfunction at day 28 post-infection with
      resultant increases in eflornithine brain delivery. Barrier integrity was never
      restored and the animals died at day 37.9 +/- 1.2. This study indicates why an
      intensive treatment regimen of eflornithine is required (poor blood-brain barrier
      penetration) and suggests a possible remedy (combining eflornithine with
      suramin). The blood-brain barrier retains functionality until a late, possibly
      terminal stage, of trypanosoma infection.

PMID- 18823368
TI  - Persistent MDMA-induced dopaminergic neurotoxicity in the striatum and substantia
      nigra of mice.
AB  - Acute administration of repeated doses of 3,4-methylenedioxymethamphetamine
      (MDMA, ecstasy) dramatically reduces striatal dopamine (DA) content, tyrosine
      hydroxylase (TH), and DA transporter-immunoreactivity in mice. In this study, we
      show for the first time the spatiotemporal pattern of dopaminergic damage and
      related molecular events produced by MDMA administration in mice. Our results
      include the novel finding that MDMA produces a significant decrease in the number
      of TH-immunoreactive neurons in the substantia nigra (SN). This decrease appears
      1 day after injection, remains stable for at least 30 days, and is accompanied by
      a dose-dependent long-lasting decrease in TH- and DA transporter-immunoreactivity
      in the striatum, which peaked 1 day after treatment and persisted for at least 30
      days, however, some recovery was evident from day 3 onwards, evidencing sprouting
      of TH fibers. No change is observed in the NAc indicating that MDMA causes
      selective destruction of DA-containing neurons in the nigrostriatal pathway,
      sparing the mesolimbic pathway. The expression of Mac-1 increased 1 day after
      MDMA treatment and glial fibrillary acidic protein increased 3 days post
      treatment in the striatum and SN but not in the NAc, in strict anatomical
      correlation with dopaminergic damage. These data provide the first evidence that
      MDMA causes persistent loss of dopaminergic cell bodies in the SN.

PMID- 18823369
TI  - An antagonistic interaction between A2B adenosine and D2 dopamine receptors
      modulates the function of rat carotid body chemoreceptor cells.
AB  - We have previously demonstrated that adenosine controls the release of
      catecholamines (CA) from carotid body (CB) acting on A2B receptors. Here, we have
      tested the hypothesis that the control is exerted via an interaction between
      adenosine A2B and dopamine D2 receptors present in chemoreceptor cells.
      Experiments were performed in vitro in CB from 3 months rats. The effect of A2B
      adenosine and D2 dopamine agonists and antagonists applied alone or in
      combination were studied on basal (20%O2) and hypoxia (10%O2)-evoked release of
      CA and cAMP content of CB. We have found that adenosine A2 agonists and D2
      antagonists dose-dependently increased basal and evoked release CA from the CB
      while A2 antagonists and D2 agonists had an inhibitory action. The existence of
      A2B-D2 receptor interaction was established because the inhibitory action of A2
      antagonists was abolished by D2 antagonists, and the stimulatory action of A2
      agonists was abolished by D2 agonists. Further, A2 agonists increased and D2
      agonist decreased cAMP content in the CB; their co-application eliminated the
      response. The present results provide direct pharmacological evidence that an
      antagonistic interaction between A2B adenosine and D2 dopamine receptors exist in
      rat CB and would explain the dopamine-adenosine interactions on ventilation
      previously observed.

PMID- 18823370
TI  - Dopaminergic system dysregulation in the mrsk2_KO mouse, an animal model of the
      Coffin-Lowry syndrome.
AB  - The Coffin-Lowry syndrome, a rare syndromic form of X-linked mental retardation,
      is caused by loss-of-function mutations in the hRSK2 (RPS6KA3) gene. To further
      investigate RSK2 (90-kDa ribosomal S6 kinase) implication in cognitive processes,
      a mrsk2_KO mouse has previously been generated as an animal model of Coffin-Lowry
      syndrome. The aim of the present study was to identify possible neurochemical
      dysregulation associated with the behavioral and morphological abnormalities
      exhibited by mrsk2_KO mice. A cortical dopamine level increase was found in
      mrsk2_KO mice that was accompanied by an over-expression of dopamine receptor of
      type 2 and the dopamine transporter. We also detected an increase of total and
      phosphorylated extracellular regulated kinase that may be responsible for the
      increased level of tyrosine hydroxylase phosphorylation also observed. By taking
      into consideration previously reported data, our results strongly suggest that
      the dopaminergic dysregulation in mrsk2_KO mice may be caused, at least in part,
      by tyrosine hydroxylase hyperactivity. This cortical hyperdopaminergia may
      explain some non-cognitive but also cognitive alterations exhibited by mrsk2_KO
      mice.

PMID- 18823371
TI  - Regulation of DARPP-32 phosphorylation by three distinct dopamine D1-like
      receptor signaling pathways in the neostriatum.
AB  - Dopamine D(1)-like receptors play a key role in dopaminergic signaling. In
      addition to G(s/olf)/adenylyl cyclase (AC)-coupled D(1) receptors, the presence
      of D(1)-like receptors coupled to G(q)/phospholipase C (PLC) has been proposed.
      Benzazepine D(1) receptor agonists are known to differentially activate
      G(s/olf)/AC and G(q)/PLC signaling. By utilizing SKF83959 and SKF83822, we
      investigated the D(1)-like receptor signaling cascades, which regulate DARPP-32
      phosphorylation at Thr34 (the PKA-site) in mouse neostriatal slices. Treatment
      with SKF83959 or SKF83822 increased DARPP-32 phosphorylation. The SKF83959- and
      SKF83822-induced increase in DARPP-32 phosphorylation was largely, but partially,
      antagonized by a D(1) receptor antagonist, SCH23390, and the residual SCH23390
      insensitive increase was abolished by an adenosine A(2A) receptor antagonist. In
      addition, the SKF83959-induced, SCH23390-sensitive increase in DARPP-32
      phosphorylation was enhanced by a PLC inhibitor. Analysis in slices from
      D(1)R/D(2)R-DARPP-32 mice revealed that both D(1) receptor agonists regulate
      DARPP-32 phosphorylation in striatonigral, but not in striatopallidal, neurons.
      Thus, dopamine D(1)-like receptors are coupled to three signaling cascades in
      striatonigral neurons: (i) SCH23390-sensitive G(s/olf)/AC/PKA, (ii) adenosine
      A(2A) receptor-dependent G(s/olf)/AC/PKA, and (iii) G(q)/PLC signaling.
      Interestingly, G(q)/PLC signaling interacts with SCH23390-sensitive
      G(s/olf)/AC/PKA signaling, resulting in its inhibition. Three signaling cascades
      activated by D(1)-like receptors likely play a distinct role in dopaminergic
      regulation of psychomotor functions.

PMID- 18823372
TI  - TNF-alpha-mediates neuroprotection against glutamate-induced excitotoxicity via
      NF-kappaB-dependent up-regulation of K2.2 channels.
AB  - Previous studies have shown that tumor necrosis factor-alpha (TNF-alpha) induces
      neuroprotection against excitotoxic damage in primary cortical neurons via
      sustained nuclear factor-kappa B (NF-kappaB) activation. The transcription factor
      NF-kappaB can regulate the expression of small conductance calcium-activated
      potassium (K(Ca)) channels. These channels reduce neuronal excitability and as
      such may yield neuroprotection against neuronal overstimulation. In the present
      study we investigated whether TNF-alpha-mediated neuroprotective signaling is
      inducing changes in the expression of small conductance K(Ca) channels.
      Interestingly, the expression of K(Ca)2.2 channel was up-regulated by TNF-alpha
      treatment in a time-dependent manner whereas the expression of K(Ca)2.1 and
      K(Ca)2.3 channels was not altered. The increase in K(Ca)2.2 channel expression
      after TNF-alpha treatment was shown to be dependent on TNF-R2 and NF-kappaB
      activation. Furthermore, activation of small conductance K(Ca) channels by 6,7
      dichloro-1H-indole-2,3-dione 3-oxime or cyclohexyl-[2-(3,5-dimethyl-pyrazol-1-yl)
      6-methyl-pyrimidin-4-yl]-amine-induced neuroprotection against a glutamate
      challenge. Treatment with the small conductance K(Ca) channel blocker apamin or
      K(Ca)2.2 channel siRNA reverted the neuroprotective effect elicited by TNF-alpha.
      We conclude that treatment of primary cortical neurons with TNF-alpha leads to
      increased K(Ca)2.2 channel expression which renders neurons more resistant to
      excitotoxic cell death.

PMID- 18823373
TI  - Predictive value of MMP-7 expression for response to chemotherapy and survival in
      patients with non-small cell lung cancer.
AB  - Fundamental studies have suggested that matrix metalloproteinases-7 (MMP-7)
      expression is associated with chemoresistance and constitutes a prognostic factor
      in several solid tumors. The present study assessed the prognostic and predictive
      value of MMP-7 in tumors of patients with advanced non-small cell lung cancer
      (NSCLC) treated with platinum-based chemotherapy. In total, 159 patients with
      stage III and IV NSCLC were retrospectively enrolled. Immunohistochemistry was
      performed to evaluate the expression of MMP-7, apoptosis-related proteins Bcl-2,
      Bax, Fas and FasL and the Ki-67 proliferation marker. The TUNEL (terminal
      deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end
      labeling) method was performed to investigate tumor apoptosis. Ninety carcinomas
      (56.6%) were identified as high expression of MMP-7. Overexpression of MMP-7 was
      more frequent in adenocarcinomas than in squamous cell carcinomas (P = 0.032).
      The expression of MMP-7 was positively related with Ki-67 index and Bcl-2, but
      not apoptosis index. MMP-7 status was correlated inversely with response to
      chemotherapy in overall patients (response rates, 20.0% and 35.8%, for patients
      with high-MMP-7 and low-MMP-7 tumors, respectively, P = 0.036), especially in
      adenocarcinoma (P = 0.021), but not in patients with squamous cell carcinomas (P
      = 0.373). The overall survival was significantly lower in NSCLC patients with
      high MMP-7 than in those with low MMP-7 (P < 0.001). A Cox regression analyses
      also demonstrated MMP-7 status to be a significant prognostic factor (hazard
      ratio, 5.49 P = 0.001). These findings suggest that the expression level of MMP-7
      in tumor cells is predictive of response to chemotherapy and outcome in patients
      with advanced NSCLC receiving platinum-based chemotherapy.

PMID- 18823374
TI  - Frequent aberrant methylation of the promoter region of sterile alpha motif
      domain 14 in pulmonary adenocarcinoma.
AB  - Aberrant methylation of promoter CpG islands is known to be a major inactivation
      mechanism of tumor-suppressor and tumor-related genes. In order to identify novel
      hypermethylated genes in early stage lung adenocarcinoma, we carried out
      methylated CpG island amplification, modified suppression subtractive
      hybridization, and methylation-specific polymerase chain reaction to identify
      aberrant methylation of CpG islands in the A/J mouse lung adenoma model, which
      histologically mimics the early stage of human pulmonary adenocarcinoma. Through
      methylated CpG island amplification, suppression subtractive hybridization, and
      differential screening, we detected five genes, three of which have human
      homologs. Two of them showed downregulation of their expression in human lung
      adenocarcinoma. Of these two genes, we selected sterile alpha motif domain 14
      (SAMD14) and further analyzed its methylation status and expression level by
      methylation-specific polymerase chain reaction and quantitative real-time
      polymerase chain reaction. Most of the lung adenocarcinoma cell lines showed
      suppressed expression of SAMD14 together with hypermethylation at the promoter
      region, although an immortalized bronchial epithelium cell line (PL16B) did not
      show hypermethylation and did express SAMD14. The expression of SAMD14 in A549
      was rescued by treatment with the demethylation agent 5-aza-2'-deoxycytidine.
      These data indicate that hypermethylation of the SAMD14 gene promoter region is
      associated with silencing of its expression. Hypermethylation at the CpG site of
      the SAMD14 promoter region was detected frequently in early invasive
      adenocarcinoma (8/24, 33.3%) but not in in situ adenocarcinoma (0/7, 0%) or
      normal lung tissue (0/31, 0%). Hypermethylation of the SAMD14 gene is a specific
      event in pulmonary adenocarcinogenesis and malignant progression.

PMID- 18823375
TI  - TS-1 enhances the effect of radiotherapy by suppressing radiation-induced hypoxia
      inducible factor-1 activation and inducing endothelial cell apoptosis.
AB  - The therapeutic effect of concurrent chemoradiotherapy with TS-1 has been
      confirmed in various solid tumors; however, the detailed mechanism of action has
      not yet been fully elucidated. In the present study, we identified hypoxia
      inducible factor-1 (HIF-1) as one of the targets of TS-1 in chemoradiotherapy. In
      growth delay assays using a tumor xenograft of non-small-cell lung carcinoma,
      H441, TS-1 treatment enhanced the therapeutic effect of single gamma-ray
      radiotherapy (14 Gy) and significantly delayed tumor growth by 1.58-fold compared
      to radiotherapy alone (P < 0.01). An optical in vivo imaging experiment using a
      HIF-1-dependent 5HRE-luc reporter gene revealed that TS-1 treatment suppressed
      radiation-induced activation of HIF-1 in the tumor xenografts. The suppression
      led to apoptosis of endothelial cells resulting in both a significant decrease in
      microvessel density (P < 0.05; vs radiation therapy alone) and a significant
      increase in apoptosis of tumor cells (P < 0.01; vs radiation therapy alone) in
      tumor xenografts. All of these results indicate that TS-1 enhances radiation
      induced apoptosis of endothelial cells by suppressing HIF-1 activity, resulting
      in an increase in radiosensitivity of the tumor cells. Our findings strengthen
      the importance of both HIF-1 and its downstream gene, such as vascular
      endothelial cell growth factor, as therapeutic targets to enhance the effect of
      radiotherapy.

PMID- 18823376
TI  - Somatostatin receptor-1 induces cell cycle arrest and inhibits tumor growth in
      pancreatic cancer.
AB  - Functional somatostatin receptors (SSTR) are lost in human pancreatic cancer.
      Transfection of SSTR-1 inhibited pancreatic cancer cell proliferation in vitro.
      We hypothesize that stable transfection of SSTR-1 may inhibit pancreatic cancer
      growth in vivo possibly through cell cycle arrest. In this study, we examined the
      expression of SSTR-1 mRNA in human pancreatic cancer tissue specimens, and
      investigated the effect of SSTR-1 overexpression on cell proliferation, cell
      cycle, and tumor growth in a subcutaneous nude mouse model. We found that SSTR-1
      mRNA was downregulated in the majority of pancreatic cancer tissue specimens.
      Transfection of SSTR-1 caused cell cycle arrest at the G(0)/G(1) growth phase,
      with a corresponding decline of cells in the S (mitotic) phase. The
      overexpression of SSTR-1 significantly inhibited subcutaneous tumor size by 71%
      and 43% (n = 5, P < 0.05, Student's t-test), and inhibited tumor weight by 69%
      and 47% (n = 5, P < 0.05, Student's t-test), in Panc-SSTR-1 and MIA-SSTR-1
      groups, respectively, indicating the potent inhibitory effect of SSTR-1 on
      pancreatic cancer growth. Our data demonstrate that overexpression of SSTR-1
      significantly inhibits pancreatic cancer growth possibly through cell cycle
      arrest. This study suggests that gene therapy with SSTR-1 may be a potential
      adjuvant treatment for pancreatic cancer.

PMID- 18823377
TI  - Antitumor and antimetastatic actions of anthrone-C-glucoside, cassialoin isolated
      from Cassia garrettiana heartwood in colon 26-bearing mice.
AB  - We examined the antitumor and antimetastatic actions of 10-hydroxy-anthrone-C
      glucoside cassialoin isolated from Cassia garrettiana heartwood in colon 26
      bearing mice. Cassialoin (5 and 10 mg/kg) inhibited tumor growth and metastasis
      to the abdomen and the expression of CD31 (angiogenesis marker) in the tumors,
      and it increased the numbers of the gamma-interferon (IFN-gamma)-positive, CD8(+)
      T and natural killer cells in the small intestine or spleen of colon 26-bearing
      mice. Furthermore, cassialoin inhibited tumor-induced angiogenesis in colon 26
      packed chamber-bearing mice. We examined the metabolic activities in the blood,
      stomach and small intestine after p.o. administration of cassialoin to mice.
      These results suggest that cassialoin might be converted to chrysophanol through
      chrysophanol-9-anthrone and metabolized to aloe-emodin from chrysophanol.
      Chrysophanol-9-anthrone inhibited vascular endothelial growth factor (VEGF) and
      matrix metallopeptidase-9 expression in colon 26 cells at 5 and 10 microM, and it
      inhibited VEGF-induced angiogenesis and migration in human umbilical vein
      endothelial cells (HUVEC) at 0.5-10 microM. Furthermore, chrysophanol-9-anthrone
      inhibited VEGF receptor (VEGFR)-2 expression and VEGF-induced VEGFR-2
      phosphorylation. Aloe-emodin also inhibited the VEGF-induced angiogenesis by
      HUVEC at 1-100 microM. Cassialoin, chrysophanol-9-anthrone and aloe-emodin
      enhanced concanavalin A-induced IFN-gamma production in splenocytes of colon 26
      bearing mice at a low concentration of 0.1 microM. From these results, it is
      suggested that the antitumor and antimetastatic actions of p.o. administered
      cassialoin may be partly due to cassialoin and its metabolites such as
      chrysophanol-9-anthrone and aloe-emodin through their anti-angiogenic activities
      and/or the modulation of the immune systems in the spleen and small intestine in
      tumor-bearing mice.

PMID- 18823378
TI  - Autophagy and autophagic cell death are next targets for elimination of the
      resistance to tyrosine kinase inhibitors.
AB  - Autophagy, a cellular degradation system has been demonstrated in some
      hematopoietic malignant cell lines, but there is much still remaining to be known
      about its role and the mechanisms. We observed the excessive autophagy in chronic
      myelogenous leukemia (CML) cell line, K562, associated with treatment of 12-O
      tetradecanoyl-phorbol-13-acetate (TPA), which can induce K562 cells to
      differentiate into megakaryocytic lineage. Confocal microscopic analysis
      demonstrated that autophagic cells did not express a megakaryocyte marker, the
      CD41 molecule, indicating that the autophagy was independent of megakaryocytic
      differentiation. After remarkable autophagic degradation, the cells finally
      underwent autophagic cell death (APCD). On the other hand, a block of TPA-induced
      autophagy by chloroquine rapidly promoted cell death that was not APCD. This
      result suggested that autophagy regulated two mechanisms in K562 cells: both the
      cell survival system and APCD. To confirm that autophagy regulates the cell
      survival system in K562 cells, imatinib was used to induce cell death in K562
      cells. Autophagy has not been considered during imatinib treatment; nonetheless,
      co-treatment with imatinib and chloroquine markedly enhanced imatinib-induced
      cell death, compared to K562 cells treated only with imatinib. Furthermore,
      imatinib-resistant cell lines, BaF3/T315I and BaF3/E255K, also underwent cell
      death by co-treatment with imatinib and chloroquine. From these data, we
      concluded that autophagy is deeply related to the cell survival system and that
      inhibition of autophagy accelerates TPA- or imatinib-induced cell death. The
      block of autophagy could be a new strategy in the treatment of CML.

PMID- 18823379
TI  - DCUN1D3, a novel UVC-responsive gene that is involved in cell cycle progression
      and cell growth.
AB  - DCUN1D3 (DCN1, defective in cullin neddylation 1, domain containing 3) was found
      during the process of high throughput screening of novel human genes associated
      with serum response element (SRE) pathway activation. The DCUN1D3 gene is highly
      conserved among vertebrates. Human DCUN1D3 complementary DNA (cDNA) encodes 304
      amino acids with an apparent molecular mass of 34 kDa. However, there has been no
      report about the function of DCUN1D3. This study detected that DCUN1D3 was
      broadly expressed in several tumor tissues and cultured cell lines; however, UVC
      irradiation of different doses significantly increased DCUN1D3 expression level
      in these cancer cell lines. Over-expression of the DCUN1D3 inhibits cell growth
      in HeLa. When the DCUN1D3 gene was silenced by siRNA in UVC-treated HeLa, the
      cell cycle in S phase was remarkably blocked; furthermore, the UVC-induced cell
      death was inhibited. In addition, DCUN1D3 localized mainly in the cytoplasm and
      perinuclear, but after UVC treatment, the DCUN1D3 gradually entered the nucleus.
      All the results above indicate that DCUN1D3 is a novel UVC-response gene involved
      in cell cycle regulation and cell survival.

PMID- 18823380
TI  - Hepatoma-derived growth factor involved in the    carcinogenesis of gastric
      epithelial cells through   promotion of cell proliferation by Erk1/2 activation.
AB  - Hepatoma-derived growth factor (HDGF) is related to tumorigenesis and the
      development of cancer; it is an independent factor associated with the prognosis
      of liver cancer, non-small cell lung cancer and pancreatic cancer. However, the
      molecular mechanism by which HDGF participates in gastric carcinogenesis and
      development as well as its functional regulation during the development of
      gastric precancerous lesions needs to be further analyzed. In the present study,
      we analyzed the effect of HDGF transfection on the proliferation and on the
      changes of mitogen-activated protein kinase (MAPK), Akt, and nuclear factor-kB
      (NF-kB) pathways in gastric cancer AGS cells. HDGF transfection significantly
      activated Erk1/2 in AGS cells and promoted anchorage-independent growth. Further
      studies showed that HDGF expression gradually increased in the gastric
      carcinogenesis process and HDGF showed a high expression in poorly differentiated
      adenocarcinoma prone to lymphoid metastasis; these findings suggest that HDGF is
      involved in the gastric carcinogenesis process and promotes proliferation and
      metastasis via Erk1/2 activation.

PMID- 18823381
TI  - Enhancement of apoptotic damage of squamous cell carcinoma cells by inhibition of
      the mitochondrial DNA repairing system.
AB  - Mitochondrial DNA (mtDNA) repair systems are thought to be associated with the
      susceptibility of cancer cells to anticancer agents. The present study
      investigated the relationship between the susceptibility to gamma-rays and the
      mtDNA repair ability of oral squamous cell carcinoma (OSC) cell lines. The levels
      of 8-hydroxy-2'-deoxyguanosine (8-OHdG) and mtDNA common deletion in both nuclear
      and mitochondrial DNA of OSC-2, OSC-3 and OSC-6 cells (radio-sensitive cell
      lines) after gamma-ray-irradiation were higher than those of OSC-1, OSC-4 and OSC
      5 cells (radio-resistant cell lines). Compared with OSC-2, OSC-3 and OSC-6 cells,
      OSC-1, OSC-4 and OSC-5 cells had higher levels of activity of phosphoinositide-3
      kinase (PI-3K)/Akt and more strongly expressed 8-hydroxyguanine DNA glycosylase
      (OGG1), DNA polymerase gamma (POLG) and mitochondrial transcription factor A
      (Tfam). Down-regulation of these mtDNA-repair-associated molecules by the RNA
      interference technique enhanced the susceptibility of OSC-2 and OSC-5 cells to
      gamma-rays, and the expression of Tfam and POLG was down-regulated by inhibitors
      of PI-3K/Akt signaling. These results indicate that the inhibition of mtDNA
      repair capacity by PI-3K/Akt signal inhibitors and OGG1 down-regulator in cancer
      cells may be a useful strategy for cancer treatment when combined with ionizing
      irradiation and chemotherapeutic drugs.

PMID- 18823382
TI  - The rate of germline mutations and large deletions of SMAD4 and BMPR1A in
      juvenile polyposis.
AB  - Juvenile polyposis (JPS) is an autosomal dominant syndrome that predisposes
      individuals to develop gastrointestinal polyps and cancer. Germline point
      mutations in SMAD4 and BMPR1A have been identified as causing JPS in
      approximately 40-60% of patients, but few studies have looked at the rate of
      large deletions. In this study, we determined the overall prevalence of genetic
      changes of SMAD4 and BMPR1A by sequencing and by screening for larger deletions.
      DNA was extracted from 102 JPS probands, and each exon and intron-exon boundary
      of SMAD4 and BMPR1A were sequenced. Coding and non-coding exons of SMAD4 and
      BMPR1A were screened for deletions with multiplex ligation-dependent probe
      amplification (MLPA). By sequencing, 20 probands had point mutations of SMAD4 and
      22 of BMPR1A. By MLPA, one proband had deletion of most of SMAD4, one of both
      BMPR1A and PTEN, one of the 5' end of BMPR1A, and another of the 5' end of SMAD4.
      The overall prevalence of SMAD4 and BMPR1A point mutations and deletions in JPS
      was 45% in the largest series of patients to date. Large deletions are less
      frequent in JPS patients, but represent other heritable causes of JPS, which
      should be screened for in pre-symptomatic genetic testing.

PMID- 18823383
TI  - Adaptation to living with a genetic condition or risk: a mini-review.
AB  - One goal of genetic counseling is to facilitate client adaptation to a genetic
      condition or risk. Adaptation refers to both the process of coming to terms with
      the implications of the condition or risk and the observable outcomes of that
      process. This review summarizes existing studies on how well clients adapt to
      living with a common chronic disease, and more specifically, a genetic condition.
      Overall, it appears that about one-third of clients do not adjust well to the
      stress of living with a genetic condition or at risk. However, the data are
      limited by inconsistencies in the conceptualization of adaptation, a paucity of
      theoretical models, poor study design and inadequate outcome measures. Well
      designed studies based upon multidimensional models are needed that focus on
      familial as well as individual adaptation. We conclude with a summary of studies
      that have explored the use of interventions to enhance adaptation and suggest
      improved client outcomes. Further research should result in evidence-based
      interventions to facilitate client adaptation that can be used effectively by
      genetic providers within the confines of their clinical work.

PMID- 18823384
TI  - Leishmania donovani depletes labile iron pool to exploit iron uptake capacity of
      macrophage for its intracellular growth.
AB  - Intracellular pathogens employ several strategies for iron acquisition from host
      macrophages for survival and growth, whereas macrophage resists infection by
      actively sequestering iron. Here, we show that instead of allowing macrophage to
      sequester iron, protozoan parasite Leishmania donovani (LD) uses a novel strategy
      to manipulate iron uptake mechanisms of the host and utilizes the taken up iron
      for its intracellular growth. To do so, intracellular LD directly scavenges iron
      from labile iron pool of macrophages. Depleted labile iron pool activates iron
      sensors iron-regulatory proteins IRP1 and IRP2. IRPs then bind to iron-responsive
      elements present in the 3' UTR of iron uptake gene transferrin receptor 1 by a
      post-transcriptional mRNA stability mechanism. Increased iron-responsive element
      IRP interaction and transferrin receptor 1 expressions in spleen-derived
      macrophages from LD-infected mice confirm that LD employs similar mechanism to
      acquire iron during infection into mammalian hosts. Increased intracellular LD
      growth by holo-transferrin supplementation and inhibited growth by iron chelator
      treatment confirm the significance of this modulated iron uptake pathway of host
      in favour of the parasite.

PMID- 18823385
TI  - A novel approach to the use of animals in studies of pain: validation of the
      canine brief pain inventory in canine bone cancer.
AB  - OBJECTIVE: To validate the Canine Brief Pain Inventory (CBPI), which is based on
      the human Brief Pain Inventory (BPI), in a canine model of spontaneous bone
      cancer. DESIGN AND PARTICIPANTS: One hundred owners of dogs with bone cancer self
      administered the CBPI on three occasions to test the reliability, validity, and
      responsiveness of the measure. OUTCOME MEASURES: Factor analysis, internal
      consistency, convergent validity, and an extreme group validation assessment were
      completed using the responses from the first administration of the CBPI. Test
      retest reliability was evaluated using two administrations of the instrument, 1
      week apart. Responsiveness was tested by comparing responses 3 weeks apart.
      RESULTS: The "severity" and "interference" factors hypothesized based on the BPI
      were demonstrated in the CBPI in dogs with bone cancer. Internal consistency was
      high (Cronbach's alpha, 0.95 and 0.93), as was test-retest reliability (kappa,
      0.73 and 0.65). Convergent validity was demonstrated with respect to quality of
      life (r = 0.49 and 0.63). Extreme group validation against normal dogs showed
      significantly higher factor scores (P < 0.001 for both). CONCLUSIONS: The CBPI
      reliably measures the same pain constructs in the companion canine model of
      spontaneous bone cancer as the BPI does in people with bone cancer. This
      innovative approach to preclinical outcomes development, validating a preclinical
      outcome measure that directly corresponds to an outcome measure routinely used in
      clinical research, applied to a readily available animal model of spontaneous
      disease could transform the predictive ability of preclinical pain studies.

PMID- 18823386
TI  - Development of a comprehensive e-learning resource in pain management.
AB  - OBJECTIVE: The prevalence of chronic nonmalignant pain (CNMP), the lack of
      confidence and reward among trainees and providers caring for patients with CNMP,
      and the lack of a comprehensive curriculum in pain management prompted the
      creation of the Virginia Commonwealth University (VCU) Chronic Nonmalignant Pain
      Management curriculum, an innovative e-learning resource. This article describes
      the development of the curriculum and presents initial evaluation data. DESIGN:
      The curriculum is organized into six modules that cover 20 specific Accreditation
      Council of Graduate Medical Education competency-based objectives. Broad content
      and effective instructional design elements promote its utility among a range of
      learner levels in a variety of medical disciplines. RESULTS: Twenty-four
      physician reviewers and over 430 trainees (medical students and graduate medical
      residents) have evaluated the curriculum. Of the respondents to course evaluation
      questions, 85.7% (366/427) stated that they would access the practice resources
      again, 86.3% (366/424) agreed that the treatment of CNMP was more important to
      them after completing the curriculum, 73.9% (312/422) stated that they would make
      changes in their behavior or practice, and 92.3% (386/418) stated that they would
      recommend the curriculum to their colleagues. Qualitative data are uniformly
      positive. Results of pretest and posttest scores and item analyses have been used
      to make content changes. CONCLUSIONS: The VCU Chronic Nonmalignant Pain
      Management curriculum is an e-learning resource that has the potential to fill a
      significant training void. Design and content changes have been made as a result
      of initial evaluation data. Data from ongoing evaluation will allow curricular
      refinement.

PMID- 18823387
TI  - A primer of ethical issues involving opioid therapy for chronic nonmalignant pain
      in a multidisciplinary setting.
AB  - OBJECTIVE: This forum presents a clinical vignette of orofacial pain and expounds
      on ethical issues related to opioid therapy in the context of multidisciplinary
      treatment. The purpose of this forum is to assist health care providers from
      different disciplines in identifying ethical issues and conflicts regarding
      opioid therapy encountered in multidisciplinary clinical pain practices. DESIGN:
      We use the case vignette and opioid therapy as a backdrop for a discussion of 1)
      an overview of ethics terminology; 2) a presentation of key ethics principles; 3)
      our conceptualization of ethical obligations of patients regarding opioid
      therapy; and 4) the process of developing an appropriate treatment plan within
      the context of the discussed ethical principles.

PMID- 18823388
TI  - Modulatory effects of transcranial direct current stimulation on laser-evoked
      potentials.
AB  - OBJECTIVE: Invasive stimulation of the motor cortex has been used for years to
      alleviate chronic intractable pain in humans. In our study, we have investigated
      the effect of transcranial direct current stimulation (tDCS), a noninvasive
      stimulation method, for manipulating the excitability of cortical motor areas on
      laser evoked potentials (LEP) and acute pain perception. DESIGNS AND SETTINGS:
      The amplitude of the N1, N2, and P2 LEP components of 10 healthy volunteers were
      evaluated prior to and following anodal, cathodal, and sham stimulation of the
      primary motor cortex. In a separate experiment subjective, pain rating scores of
      16 healthy subjects in two perceptual categories (warm sensation, mild pain) were
      also analyzed. RESULTS: Cathodal tDCS significantly reduced the amplitude of N2
      and P2 components compared with anodal or sham stimulation. However, neither of
      the tDCS types modified significantly the laser energy values necessary to induce
      moderate pain. In a separate experiment, cathodal stimulation significantly
      diminished mild pain sensation only when laser-stimulating the hand contralateral
      to the side of tDCS, while anodal stimulation modified warm sensation.
      CONCLUSIONS: The possible underlying mechanisms of our findings in view of recent
      neuroimaging studies are discussed. To our knowledge this study is the first to
      demonstrate the mild antinociceptive effect of tDCS over the primary motor cortex
      in healthy volunteers.

PMID- 18823389
TI  - Deconstructing the litigious pain patient.

PMID- 18823390
TI  - Oxygen and the spatial structure of microbial communities.
AB  - Oxygen has two faces. On one side it is the terminal electron acceptor of aerobic
      respiration - the most efficient engine of energy metabolism. On the other hand,
      oxygen is toxic because the reduction of molecular O2 creates reactive oxygen
      species such as the superoxide anion, peroxide, and the hydroxyl radical.
      Probably most prokaryotes, and virtually all eukaryotes, depend on oxygen
      respiration, and we show that the ambiguous relation to oxygen is both an
      evolutionary force and a dominating factor driving functional interactions and
      the spatial structure of microbial communities.We focus on microbial communities
      that are specialised for life in concentration gradients of oxygen, where they
      acquire the full panoply of specific requirements from limited ranges of PO2,
      which also support the spatial organisation of microbial communities. Marine and
      lake sediments provide examples of steep O2 gradients, which arise because
      consumption or production of oxygen exceeds transport rates of molecular
      diffusion. Deep lakes undergo thermal stratification in warm waters, resulting in
      seasonal anaerobiosis below the thermocline, and lakes with a permanent
      pycnocline often have permanent anoxic deep water. The oxycline is here
      biologically similar to sediments, and it harbours similar microbial biota, the
      main difference being the spatial scale. In sediments, transport is dominated by
      molecular diffusion, and in the water column, turbulent mixing dominates vertical
      transport. Cell size determines the minimum requirement of aerobic organisms. For
      bacteria (and mitochondria), the half-saturation constant for oxygen uptake
      ranges within 0.05-0.1% atmospheric saturation; for the amoeba Acanthamoeba
      castellanii it is 0.2%, and for two ciliate species measuring around 150 microm,
      it is 1-2 % atmospheric saturation. Protection against O2 toxicity has an
      energetic cost that increases with increasing ambient O2 tension. Oxygen sensing
      seems universal in aquatic organisms. Many aspects of oxygen sensing are
      incompletely understood, but the mechanisms seem to be evolutionarily conserved.
      A simple method of studying oxygen preference in microbes is to identify the
      preferred oxygen tension accumulating in O2 gradients. Microorganisms cannot
      sense the direction of a chemical gradient directly, so they use other devices to
      orient themselves. Different mechanisms in different prokaryotic and eukaryotic
      microbes are described. In O2 gradients, many bacteria and protozoa are
      vertically distributed according to oxygen tension and they show a very limited
      range of preferred PO2. In some pigmented protists the required PO2 is contingent
      on light due to photochemically generated reactive oxygen species. In protists
      that harbour endosymbiotic phototrophs, orientation towards light is mediated
      through the oxygen production of their photosynthetic symbionts. Oxygen plays a
      similar role for the distribution of small metazoans (meiofauna) in sediments,
      but there is little experimental evidence for this. Thus the oxygenated sediments
      surrounding ventilated animal burrows provide a special habitat for metazoan
      meiofauna as well as unicellular organisms.

PMID- 18823391
TI  - Robustness: confronting lessons from physics and biology.
AB  - The term robustness is encountered in very different scientific fields, from
      engineering and control theory to dynamical systems to biology. The main question
      addressed herein is whether the notion of robustness and its correlates
      (stability, resilience, self-organisation) developed in physics are relevant to
      biology, or whether specific extensions and novel frameworks are required to
      account for the robustness properties of living systems. To clarify this issue,
      the different meanings covered by this unique term are discussed; it is argued
      that they crucially depend on the kind of perturbations that a robust system
      should by definition withstand. Possible mechanisms underlying robust behaviours
      are examined, either encountered in all natural systems (symmetries, conservation
      laws, dynamic stability) or specific to biological systems (feedbacks and
      regulatory networks). Special attention is devoted to the (sometimes
      counterintuitive) interrelations between robustness and noise. A distinction
      between dynamic selection and natural selection in the establishment of a robust
      behaviour is underlined. It is finally argued that nested notions of robustness,
      relevant to different time scales and different levels of organisation, allow one
      to reconcile the seemingly contradictory requirements for robustness and
      adaptability in living systems.

PMID- 18823392
TI  - Hypotheses, mechanisms and trade-offs of tolerance and adaptation to serpentine
      soils: from species to ecosystem level.
AB  - Understanding the relative importance of the abiotic environment and species
      interactions in determining the distribution and abundance of organisms has been
      a challenge in ecological research. Serpentine substrata are stressful
      environments for plant growth due to multiple limitations, collectively called
      the "serpentine syndrome". In the present review, our aim is not only to describe
      recent work in serpentine ecology, but also to highlight specific mechanisms of
      species tolerance and adaptation to serpentine soils and their effects on
      community structure and ecosystem functioning. We present hypotheses of the
      development of serpentine endemism and a description of functional traits of
      serpentine plants together with a synthesis of species interactions in serpentine
      soils and their effects on community structure and ecosystem productivity. In
      addition, we propose hypotheses about the effects of the 'serpentine syndrome' on
      ecosystem processes including productivity and decomposition.

PMID- 18823394
TI  - Cross-sectional analysis of testosterone therapies in hypopituitary men on stable
      pituitary hormone replacement.
AB  - OBJECTIVE: The last decade has seen a proliferation in options for testosterone
      replacement. However, little is known as to the benefits of different treatment
      modalities. Our objective was to determine the testosterone prescription pattern
      and to examine the impact on various outcome measures. SUBJECTS AND METHODS: A
      total of 816 adult-onset hypopituitary males on stable pituitary replacement for
      at least 1 year were identified from the KIMS database. Patients were classified
      as either eugonadal (n = 106), or hypogonadal (n = 710) on intramuscular (IM, n =
      558), oral (n = 74), transdermal (n = 61), and depot (n = 17) testosterone.
      RESULTS: After 1 year of stable pituitary replacement therapy, body composition,
      cardiovascular parameters, GH replacement and quality of life were not
      significantly different in androgen-replaced hypogonadal patients compared to
      eugonadal patients. There were no differences in outcome variables within the
      hypogonadal group according to the testosterone replacement regimen used and no
      difference in response to GH therapy. CONCLUSIONS: The majority of hypopituitary
      patients in the last decade have received IM testosterone. Body composition,
      cardiovascular parameters, GH replacement and quality of life were not different
      between eugonadal and hypogonadal patients and were not differentially affected
      by the mode of testosterone replacement. These findings are reassuring that there
      is no major difference in response to different testosterone replacement
      regimens.

PMID- 18823393
TI  - Stoichiometry of soil enzyme activity at global scale.
AB  - Extracellular enzymes are the proximate agents of organic matter decomposition
      and measures of these activities can be used as indicators of microbial nutrient
      demand. We conducted a global-scale meta-analysis of the seven-most widely
      measured soil enzyme activities, using data from 40 ecosystems. The activities of
      beta-1,4-glucosidase, cellobiohydrolase, beta-1,4-N-acetylglucosaminidase and
      phosphatase g(-1) soil increased with organic matter concentration; leucine
      aminopeptidase, phenol oxidase and peroxidase activities showed no relationship.
      All activities were significantly related to soil pH. Specific activities, i.e.
      activity g(-1) soil organic matter, also varied in relation to soil pH for all
      enzymes. Relationships with mean annual temperature (MAT) and precipitation (MAP)
      were generally weak. For hydrolases, ratios of specific C, N and P acquisition
      activities converged on 1 : 1 : 1 but across ecosystems, the ratio of C : P
      acquisition was inversely related to MAP and MAT while the ratio of C : N
      acquisition increased with MAP. Oxidative activities were more variable than
      hydrolytic activities and increased with soil pH. Our analyses indicate that the
      enzymatic potential for hydrolyzing the labile components of soil organic matter
      is tied to substrate availability, soil pH and the stoichiometry of microbial
      nutrient demand. The enzymatic potential for oxidizing the recalcitrant fractions
      of soil organic material, which is a proximate control on soil organic matter
      accumulation, is most strongly related to soil pH. These trends provide insight
      into the biogeochemical processes that create global patterns in ecological
      stoichiometry and organic matter storage.

PMID- 18823395
TI  - Intravenous zoledronate improves bone density in adults with cystic fibrosis
      (CF).
AB  - OBJECTIVE: Reduced bone mineral density (BMD) and increased rates of atraumatic
      fracture are observed in cystic fibrosis (CF) patients, causing increasing
      morbidity as this population ages. The study aimed to assess the safety,
      tolerability and effect on BMD of intravenous zoledronate in adults with CF and
      osteopaenia. DESIGN: Randomized, double-blind, placebo-controlled clinical trial.
      SETTING: Adult CF outpatient clinics at two hospitals. PATIENTS: Twenty-two non
      transplanted CF patients aged > or = 18 years with a bone densitometry T-score of
      < -1.5 at one of three sites (lumbar spine, femoral neck, distal forearm) were
      studied. Participants were randomized to receive either 2 mg zoledronate i.v. (n
      = 10) or normal saline (placebo, n = 12) every 3 months for 2 years (8
      infusions). All participants received calcium and vitamin D supplements twice
      daily. MEASUREMENTS: Percentage change in areal BMD from baseline. RESULTS:
      Lumbar spine BMD increased from baseline more with zoledronate than placebo at 6
      months (5.35 +/- 0.76 vs. 1.19 +/- 1.20%, P = 0.012), 12 months (6.6 +/- 1.5 vs.
      0.35 +/- 1.55%, P = 0.011) and 24 months (6.14 +/- 1.86 vs. 0.44 +/- 0.10, P =
      0.021). Femoral neck BMD increased more after zoledronate than placebo at 6
      months (3.2 +/- 1.6 vs.-1.43 +/- 0.43%, P = 0.019), 12 months (4.12 +/- 1.8 vs.
      1.59 +/- 1.4%, P = 0.024) and 24 months (4.23 +/- 1.3 vs.-2.5 +/- 1.41%, P =
      0.0028). Forearm BMD did not change. Zoledronate was associated with flu-like and
      musculoskeletal side effects, particularly after the first infusion. There were
      no fractures in either group. CONCLUSION: Intravenous zoledronate was
      significantly more effective than placebo for increasing BMD in adults with CF
      and osteopaenia, but side effects limited its tolerability.

PMID- 18823397
TI  - The classification and diagnosis of erythrocytosis.
AB  - An absolute erythrocytosis is present when the red cell mass is raised and the
      haematocrit is elevated above prescribed limits. Causes of an absolute
      erythrocytosis can be primary where there is an intrinsic problem in the bone
      marrow and secondary where there an event outside the bone marrow driving
      erythropoiesis. This can further be divided into congenital and acquired causes.
      There remain an unexplained group idiopathic erythrocytosis. Investigation
      commencing with thorough history taking and examination and then investigation
      depending on initial features is required. Clear simple criteria for
      polycythaemia vera are now defined. Those who do not fulfil these criteria
      require further investigation depending on the clinical scenario and initial
      results. The erythropoietin level provides some guidance as to the direction in
      which to proceed and the order and extent of investigation necessary in an
      individual patient. It should thus be possible to make an accurate diagnosis in
      the majority of patients.

PMID- 18823396
TI  - Evidence for recombination between a sialidase (nanH) of Actinomyces naeslundii
      and Actinomyces oris, previously named 'Actinomyces naeslundii genospecies 1 and
      2'.
AB  - Actinomyces spp., predominant members of human oral biofilms, may use
      extracellular sialidase to promote adhesion, deglycosylate immunoglobulins and
      liberation of nutrients. Partial nanH gene sequences (1,077 bp) from Actinomyces
      oris (n=74), Actinomyces naeslundii (n=30), Actinomyces viscosus (n=1) and
      Actinomyces johnsonii (n=2) which included the active-site region and the
      bacterial neuraminidase repeats (BNRs) were compared. The sequences were aligned
      and each species formed a distinct cluster with five isolates having intermediate
      positions. These five isolates (two A. oris and three A. naeslundii) exhibited
      interspecies recombination. The nonsynonymous/synonymous ratio was <1 for both A.
      oris and A. naeslundii indicating that nanH in both species is under stabilizing
      selective pressure; nonsynonymous mutations are not selected. However, for A.
      oris significant negative values in tests for neutral selection suggested the
      rate of mutation in A. oris was greater than in A. naeslundii but with selection
      against nonsynonymous mutations. This was supported by the observation that the
      frequency of polymorphic sites in A. oris, which were monomorphic in A.
      naeslundii was significantly greater than the frequency of polymorphic sites in
      A. naeslundii which were monomorphic in A. oris (chi(2)=7.011; P=0.00081). The
      higher proportions of A. oris in the oral biofilm might be explained by the
      higher mutation rate facilitating an increased ability to respond successfully to
      environmental stress.

PMID- 18823398
TI  - Quantifying potential recharge in mantled sinkholes using ERT.
AB  - Potential recharge through thick soils in mantled sinkholes was quantified using
      differential electrical resistivity tomography (ERT). Conversion of time series
      two-dimensional (2D) ERT profiles into 2D volumetric water content profiles using
      a numerically optimized form of Archie's law allowed us to monitor temporal
      changes in water content in soil profiles up to 9 m in depth. Combining Penman
      Monteith daily potential evapotranspiration (PET) and daily precipitation data
      with potential recharge calculations for three sinkhole transects indicates that
      potential recharge occurred only during brief intervals over the study period and
      ranged from 19% to 31% of cumulative precipitation. Spatial analysis of ERT
      derived water content showed that infiltration occurred both on sinkhole flanks
      and in sinkhole bottoms. Results also demonstrate that mantled sinkholes can act
      as regions of both rapid and slow recharge. Rapid recharge is likely the result
      of flow through macropores (such as root casts and thin gravel layers), while
      slow recharge is the result of unsaturated flow through fine-grained sediments.
      In addition to developing a new method for quantifying potential recharge at the
      field scale in unsaturated conditions, we show that mantled sinkholes are an
      important component of storage in a karst system.

PMID- 18823399
TI  - Vulnerability of a public supply well in a karstic aquifer to contamination.
AB  - To assess the vulnerability of ground water to contamination in the karstic Upper
      Floridan aquifer (UFA), age-dating tracers and selected anthropogenic and
      naturally occurring compounds were analyzed in multiple water samples from a
      public supply well (PSW) near Tampa, Florida. Samples also were collected from 28
      monitoring wells in the UFA and the overlying surficial aquifer system (SAS) and
      intermediate confining unit located within the contributing recharge area to the
      PSW. Age tracer and geochemical data from the earlier stage of the study (2003
      through 2005) were combined with new data (2006) on concentrations of sulfur
      hexafluoride (SF(6)), tritium ((3)H), and helium-3, which were consistent with
      binary mixtures of water for the PSW dominated by young water (less than 7
      years). Water samples from the SAS also indicated mostly young water (less than 7
      years); however, most water samples from monitoring wells in the UFA had lower
      SF(6) and (3)H concentrations than the PSW and SAS, indicating mixtures
      containing high proportions of older water (more than 60 years). Vulnerability of
      the PSW to contamination was indicated by predominantly young water and elevated
      nitrate-N and volatile organic compound concentrations that were similar to those
      in the SAS. Elevated arsenic (As) concentrations (3 to 19 microg/L) and higher
      As(V)/As(III) ratios in the PSW than in water from UFA monitoring wells indicate
      that oxic water from the SAS likely mobilizes As from pyrite in the UFA matrix.
      Young water found in the PSW also was present in UFA monitoring wells that tap a
      highly transmissive zone (43- to 53-m depth) in the UFA.

PMID- 18823400
TI  - PRO-GRADE: GIS toolkits for ground water recharge and discharge estimation.
AB  - PRO-GRADE is an ESRI ArcGIS 9.2 plug-in package that consists of two separate
      toolkits: (1) the pattern recognition organizer for geographic information system
      (PRO-GIS) and (2) the ground water recharge and discharge estimator for GIS
      (GRADE-GIS). PRO-GIS is a collection of several existing image-processing
      algorithms into one user interface to offer the flexibility to extract spatial
      patterns according to the user's needs. GRADE-GIS is a ground water recharge and
      discharge estimation interface using a mass balance method that requires only
      hydraulic conductivity, water table, and bedrock elevation data for simulating
      two-dimensional steady-state unconfined aquifers. PRO-GRADE was developed to
      assist ongoing assessments of the water resources in Illinois and Wisconsin, and
      is being used to assist several ground water resource studies in several
      locations in the United States. The advantage of using PRO-GRADE is to enable
      fast production of initial recharge and discharge maps that can be further
      enhanced by using a follow-up ground water flow model with parameter estimation
      codes. PRO-GRADE leverages ArcGIS to provide a computer-assisted framework to
      support expert judgment in order to efficiently select alternative recharge and
      discharge maps that can be used as (1) guidelines for field study planning and
      decision making; (2) initial conditions for numerical simulation; and (3)
      screening for alternative model selection and prediction/parameter uncertainty
      evaluation. In addition, PRO-GRADE allows for more easy and rapid correlation of
      those maps with other hydrologically relevant geospatial data.

PMID- 18823401
TI  - Biased monitoring of fresh water-salt water mixing zone in coastal aquifers.
AB  - In coastal aquifers, significant vertical hydraulic gradients are formed where
      fresh water and underlying salt water discharge together upward to the seafloor.
      Monitoring boreholes may act as "short circuits" along these vertical gradients,
      connecting between the higher and the lower hydraulic head zones. When a sea tide
      is introduced, the fluctuations of both the water table and the depth of the
      mixing zone are also biased due to this effect. This problem is intensified in
      places of long-screen monitoring boreholes, which are common in many places in
      the world. For example, all approximately 500 boreholes of the fresh water-salt
      water mixing zone in the coastal aquifer of Israel are installed with 10 to 50 m
      long screens. We present field measurements of these fluctuations, along with a
      three-dimensional numerical model. We find that the in-well fluctuation magnitude
      of the mixing zone is an order of magnitude larger than that in the porous media
      of the actual aquifer. The primary parameters that affect the magnitude of this
      bias are the anisotropy of the aquifer conductivity and the borehole hydraulic
      parameters. With no sea tide, borehole interference is higher for the anisotropic
      case because the vertical hydraulic gradients are high. When tides are
      introduced, the amplitude of the mixing zone fluctuation is higher for the
      isotropic case because the overall effective hydraulic conductivity is greater
      than the conductivity in the anisotropic case. In the aquifer, the fresh water
      salt water mixing zone fluctuations are dampened, and tens of meters inland from
      the shoreline, the fluctuations are on the order of few centimeters.

PMID- 18823402
TI  - Introduction to hydromechanical well tests in fractured rock aquifers.
AB  - This article introduces hydromechanical well tests as a viable field method for
      characterizing fractured rock aquifers. These tests involve measuring and
      analyzing small displacements along with pressure transients. Recent developments
      in equipment and analyses have simplified hydromechanical well tests, and this
      article describes initial field results and interpretations during slug and
      constant-rate pumping tests conducted at a site underlain by fractured biotite
      gneiss in South Carolina. The field data are characterized by displacements of
      0.3 microm to more than 10 microm during head changes up to 10 m. Displacements
      are a hysteretic function of hydraulic head in the wellbore, with displacements
      late in a well test always exceeding those at similar wellbore pressures early in
      the test. Displacement measurements show that hydraulic aperture changes during
      well tests, and both scaling analyses and field data suggest that T changed by a
      few percent per meter of drawdown during slug and pumping tests at our field
      site. Preliminary analyses suggest that displacement data can be used to improve
      estimates of storativity and to reduce nonuniqueness during hydraulic well tests
      involving single wells.

PMID- 18823403
TI  - A review of minimally invasive cosmetic procedures.
AB  - In today's society the desire to maintain a youthful appearance has driven the
      development of minimally invasive dermatological procedures that are designed to
      rejuvenate the ageing face. The aim of this review is to present evidence for the
      use of techniques which can easily be incorporated into outpatient dermatology
      practice with low overhead expenditure. For this reason, laser and light-based
      treatments have been omitted. This review will instead focus on chemical peels,
      intradermal fillers and botulinum toxin. These techniques address the main
      aspects of facial ageing, namely photodamage, volume loss and dynamic lines,
      which correlate anatomically to skin, subcutaneous fat and muscle. A combination
      of such techniques will provide the practitioner with a reasonable portfolio of
      treatments for a balanced, holistic result.

PMID- 18823404
TI  - Germline expression of H-Ras(G12V) causes neurological deficits associated to
      Costello syndrome.
AB  - Costello syndrome (CS) is a rare congenital disorder caused by germline
      activation of H-Ras oncogenes. A mouse model of CS generated by introduction of
      an oncogenic Gly12Val mutation in the mouse H-Ras locus using homologous
      recombination in embryonic stem (ES) cells has been recently described. These
      mice phenocopied some of the abnormalities observed in patients with CS,
      including facial dysmorphia and cardiomyopathies. We investigated here their
      neurological and behavioral phenotype. The analysis of H-Ras(G12V) mice revealed
      phenotypes that resembled the hyperemotivity, hypersensibility and cognitive
      impairments observed in children with CS. Stronger neurological deficits were
      found in the analysis of mice homozygous for this mutation than in the analysis
      of heterozygous mice, suggesting the existence of a gene dose effect. These mice
      represent the first mouse model for CS, offering an experimental tool to study
      the molecular and physiological alterations underlying the neurological
      manifestations of CS and to test new therapies aimed at preventing or
      ameliorating the cognitive and emotional impairments associated to this
      condition.

PMID- 18823405
TI  - Cognitive function in facioscapulohumeral dystrophy correlates with the molecular
      defect.
AB  - Previous studies based on case descriptions and neuroradiological findings have
      suggested central nervous system (CNS) involvement in facioscapulohumeral
      dystrophy. The aim of this work is to explore the relationship between
      cognitive/personality pattern and the underlying molecular defect for this
      muscular dystrophy. We performed a wide-ranging neuropsychological assessment of
      34 molecularly confirmed facioscapulohumeral dystrophy patients and 49 control
      subjects, all of whom also received the Millon-II Multiaxial Clinical Inventory
      (MCMI-II). Patients and controls show mild learning-level differences in the
      neuropsychological profile, and only the hysteriform scale is statistically
      higher in patients than controls. The patients' intelligence quotient (IQ) is
      related to the size of the deleted fragment but not to the degree of muscular
      impairment. The results of this study indicate a cut-off point and two distinct
      cognitive profiles in facioscapulohumeral dystrophy, depending on the patients'
      molecular defect: patients with a fragment size > 24 kb show a relatively normal
      cognitive pattern, whereas those with a fragment size < or = 24 kb show a
      significantly reduced IQ and difficulties with verbal function and visuo
      constructive tasks. This work provides more evidence for the involvement of the
      CNS in facioscapulohumeral dystrophy and suggests that the fragment size should
      be taken into account in the clinical management of facioscapulohumeral dystrophy
      as it has a predictive value on the cognitive phenotype.

PMID- 18823406
TI  - Masitinib is safe and effective for the treatment of canine mast cell tumors.
AB  - BACKGROUND: Activation of the KIT receptor tyrosine kinase is associated with the
      development of canine mast cell tumors (MCT). HYPOTHESIS/OBJECTIVE: To evaluate
      the efficacy of masitinib, a potent and selective inhibitor of KIT, in the
      treatment of canine MCT. ANIMALS: Two hundred and two client-owned dogs with
      nonmetastatic recurrent or nonresectable grade II or III MCT. METHODS: Double
      blind, randomized, placebo-controlled phase III clinical trial. Dogs were
      administered masitinib (12.5 mg/kg/d PO) or a placebo. Time-to-tumor progression
      (TTP), overall survival, objective response at 6 months, and toxicity were
      assessed. RESULTS: Masitinib increased overall TTP compared with placebo from 75
      to 118 days (P = .038). This effect was more pronounced when masitinib was used
      as first-line therapy, with an increase in the median TTP from 75 to 253 days (P
      = .001) and regardless of whether the tumors expressed mutant (83 versus not
      reached [P = .009]) or wild-type KIT (66 versus 253 [P = .008]). Masitinib was
      generally well tolerated, with mild (grade I) or moderate (grade II) diarrhea or
      vomiting as the most common adverse events. CONCLUSIONS AND CLINICAL IMPORTANCE:
      Masitinib is safe and effective at delaying tumor progression in dogs presenting
      with recurrent or nonresectable grade II or III nonmetastatic MCT.

PMID- 18823407
TI  - Successful resolution of cryptococcal meningitis and optic neuritis in an adult
      horse with oral fluconazole.

PMID- 18823408
TI  - Hypoglycemia and hyperlactatemia associated with lymphoma in an Angus cow.

PMID- 18823409
TI  - The TrialNet Natural History Study of the Development of Type 1 Diabetes:
      objectives, design, and initial results.
AB  - OBJECTIVES: TrialNet's goal to test preventions for type 1 diabetes has created
      an opportunity to gain new insights into the natural history of pre-type 1
      diabetes. The TrialNet Natural History Study (NHS) will assess the predictive
      value of existing and novel risk markers for type 1 diabetes and will find
      subjects for prevention trials. RESEARCH DESIGN AND METHODS: The NHS is a three
      phase, prospective cohort study. In phase 1 (screening), pancreatic
      autoantibodies (glutamic acid decarboxylase, insulin, ICA-512, and islet cell
      antibodies) are measured. Phase 2 (baseline risk assessment) includes oral
      glucose tolerance tests (OGTTs) in antibody-positive subjects and estimation of 5
      yr diabetes risks according to the OGTT and number of confirmed positive antibody
      tests. Phase 3 (follow-up risk assessments) requires OGTTs every 6 months. In
      phases 2 and 3, samples are collected for future tests of T-lymphocyte function,
      autoantibody isotypes, RNA gene expression, and proteomics. The primary outcome
      is diabetes onset. RESULTS: Of 12 636 relatives screened between March 2004 and
      December 2006, 605 (4.8%) were positive for at least one biochemical antibody. Of
      these, 322 were confirmed antibody positive and completed phase 2, of whom 296
      subjects were given preliminary 5-yr diabetes risks of <25% (n = 132), > or =25%
      (n = 36), and > or =50% (n = 128) where the latter two categories represent
      different subjects based on number of confirmed positive antibodies (2, > or
      =25%; 3 or more, > or =50%) and/or an abnormal OGTT (> or =50%). CONCLUSIONS: The
      NHS is identifying potential prevention trial subjects and is assembling a large
      cohort that will provide new natural history information about pre-type 1
      diabetes. Follow-up to diabetes will help establish the biological significance
      and clinical value of novel type 1 diabetes risk markers.

PMID- 18823410
TI  - Participant and parent experiences in the oral insulin study of the Diabetes
      Prevention Trial for Type 1 Diabetes.
AB  - OBJECTIVE: To assess the experiences of participants and parents of children in
      the oral insulin study of the Diabetes Prevention Trial - Type 1. METHOD: Before
      trial results were publicized, surveys were completed by 124 participants and 219
      parents of children in the oral trial. RESULTS: Although most of those surveyed
      were positive about the trial, survey results suggest that participant
      perspective (adult, child, parent, and gender), study procedures, and beliefs
      about placebo vs. active drug assignment have important implications for planning
      future clinical trials. Parents and children reported greater distress, worry,
      and difficulty making the decision to join the trial compared with adult
      participants. Mothers and female participants were particularly interested in
      additional psychosocial support during the study. Random assignment was viewed
      negatively by both parents and children, and close observation for diabetes onset
      was viewed as the most favorable aspect of the study. Adherence to study
      procedures declined over time and behaviors outside the study protocol to
      prevent/delay diabetes onset were common, particularly among those who believed
      the participant was taking a placebo. Children and respondents who believed that
      the participant was taking the active drug expressed confidence in oral insulin's
      ability to delay or prevent type 1 diabetes. CONCLUSIONS: Although most
      participants were positive about the trial and many expressed optimism about the
      intervention's potential for success, future trials need to address negative
      reactions to random assignment, the unique concerns of children and their
      parents, declining adherence, and behaviors - external to the trial - designed to
      delay or prevent diabetes.

PMID- 18823411
TI  - Transverse patterning dissociates human EEG theta power and hippocampal BOLD
      activation.
AB  - Theta oscillations (4-8 Hz) are often modulated in human electroencephalogram
      (EEG) studies of memory, whereas overlapping frequencies dominate rodent
      hippocampal EEG. An emerging parallelism between theta reactivity and hippocampal
      functional magnetic resonance imaging activation has suggested a homology between
      theta activity in humans and rodents, representing a process of cortico
      hippocampal interaction involved in memory. In the present study, we investigated
      EEG reactivity during performance of a relational memory task that induces a
      negative hippocampal blood oxygenation level dependent (BOLD) signal change,
      compared to a nonrelational control condition. Relational trials induced theta
      increases and alpha decreases. Low Resolution Electromagnetic Brain Tomography
      estimates localized theta and alpha modulation to frontal midline and parietal
      midline cortices, respectively, both of which exhibit negative BOLD responses in
      this task. Thus, theta and alpha dynamics are dissociable from positive BOLD
      activation, and may, in fact, colocalize with negative BOLD responses.

PMID- 18823412
TI  - The effects of 28 hours of sleep deprivation on respiratory sinus arrhythmia
      during tasks with low and high controlled attention demands.
AB  - Task performance while sleep deprived may be moderated by the controlled
      attention required by the task (Pilcher, Band, Odle-Dusseau, & Muth, 2007). This
      study examined the effects of 28 h of sleep deprivation on respiratory sinus
      arrhythmia (RSA) during tasks with low and high controlled attention demands. The
      results showed that RSA increased throughout the night for both task types, but
      was consistently reduced during the low compared to high controlled attention
      tasks. The increase in RSA was linear for the high controlled attention tasks but
      curvilinear for the low ones. Hence, RSA followed a circadian pattern during the
      low controlled attention tasks but not the high ones. These results suggest that
      the effects of sleep deprivation on task performance may be moderated by
      parasympathetic activity and task type, and this has implications for task
      assignment during sustained operations that cause sleep deprivation.

PMID- 18823413
TI  - Influence of successive bouts of fatiguing exercise on perceptual and
      physiological markers during an incremental exercise test.
AB  - The purpose of this study was to examine the effects of a succession of fatiguing
      stages, on ratings of perceived exertion (RPE) and estimated time limits (ETL)
      during an incremental exercise test. Twenty-seven cyclists performed a continuous
      incremental test and a discontinuous test with randomized workloads. A linear
      mixed model was used to compare the RPE, ETL, respiratory gas, heart rate, and
      blood data obtained during the two exercise tests. RPE and ETL were not
      significantly different between the tests. Ventilation, breathing frequency,
      heart rate, and blood lactate concentration were significantly higher during the
      last incremental test workloads. In conclusion, although the incremental exercise
      test generated higher cardiorespiratory and muscular workloads than observed
      during the randomized exercise test, most likely due to a greater fatiguing
      process, these higher workloads did not influence the perceptual response.

PMID- 18823414
TI  - Affective modulation of inspiratory motor drive.
AB  - The present study aimed to explore inspiratory motor drive as measured by
      inspiratory occlusion pressure (P100) during affective picture viewing. P100 is
      the decrease in mouth pressure that develops 100 ms after an inspiratory effort
      against a closed breathing circuit. The P100 is a measure of the "central
      respiratory drive." Seventy-eight healthy women viewed four pictures series (160
      s) varying in content: neutral, positive, threat, or pain. They also rated each
      picture series on pleasantness and arousal. An occlusion was applied at the onset
      of inspiration in 33% of the breaths. The threat and the pain picture series were
      associated with an increased P100 and were rated as most unpleasant and highest
      in arousal. We conclude that inspiratory motor drive is affectively modulated and
      is a measure of the respiratory response to threatful stimuli.

PMID- 18823415
TI  - Cardiovascular dynamics in blood phobia: evidence for a key role of sympathetic
      activity in vulnerability to syncope.
AB  - This study was aimed at clarifying the mechanism predisposing people with blood
      phobia to syncope by investigating the complete hemodynamic response pattern and
      the underlying autonomic control. Blood phobics and controls were shown 3 film
      clips: phobia-related, phobia-unrelated, and neutral. Hemodynamic responses were
      recorded using impedance cardiography and Finapres. Preejection period and
      respiratory sinus arrhythmia were employed as indices of cardiac sympathetic and
      parasympathetic activity. Self-ratings of emotion were also collected. Blood
      phobics displayed global heart rate and cardiac output increases to the phobic
      film, mediated by augmented cardiac sympathetic activity. Systolic blood pressure
      and total peripheral resistance markedly declined, with no evidence of diphasic
      reaction or parasympathetic activation. An impaired vasomotor response under
      sympathetic control might be the key mechanism underlying the phobic
      dysfunctional response.

PMID- 18823416
TI  - Modulation of the human mirror neuron system during cognitive activity.
AB  - In this experiment we examined the relationship between the mirror neuron system
      and increased attention caused by task demands. Whole head MEG recordings were
      made from 13 participants who were asked to passively observe finger movement
      sequences, observe these sequences with the knowledge they would later have to
      perform the sequence presented, and finally, to perform a nonmotor mathematics
      task based on the finger-movement sequences. Beta-band (15-35 Hz) sensorimotor
      desynchronization was found in overlapping areas during passive observation and
      in a separate motor execution condition, indicating the activity of the human
      mirror neuron system. The beta desynchronization in these areas was enhanced
      relative to passive viewing when participants had to watch the stimuli to later
      imitate and when they performed the mathematics task, indicating that mirror
      neuron system activity can be modulated by attention.

PMID- 18823417
TI  - Comparing low frequency heart rate variability and preejection period: two sides
      of a different coin.
AB  - It has been hypothesized that the ratio of heart rate variability in the low-
      (LF) and high- (HF) frequency bands may capture variation in cardiac sympathetic
      control. Here we tested the temporal stability of the LF/HF ratio in 24-h
      ambulatory recordings and compared this ratio to the preejection period (PEP), an
      established measure of cardiac sympathetic control. Good temporal stability was
      found across a period of 3.3 years (.46<r<.78), but the LF/HF ratio did not show
      the expected negative correlation to PEP, either between or within subjects. We
      conclude that the evidence to support the LF/HF ratio as a potential marker of
      cardiac sympathetic control in epidemiology-scaled research is currently
      insufficient.

PMID- 18823418
TI  - The Complex Trial Protocol (CTP): a new, countermeasure-resistant, accurate, P300
      based method for detection of concealed information.
AB  - A new P300-based concealed information test is described. A rare probe or
      frequent irrelevant stimulus appears in the same trial in which a target or
      nontarget later appears. One response follows the first stimulus and uses the
      same button press regardless of stimulus type. A later second stimulus then
      appears: target or nontarget. The subject presses one button for a target,
      another for a nontarget. A P300 to the first stimulus indicates probe
      recognition. One group was tested in 3 weeks for denied recognition of familiar
      information. Weeks 1 and 3 were guilty conditions; Week 2 was a countermeasure
      (CM) condition. The probe-irrelevant differences were significant in all weeks,
      and percent hits were >90%. Attempted CM use was detectable via elevated reaction
      time to the first stimulus. In a replication, results were similar. False
      positive rates for both studies varied from 0 to .08, yielding J. B. Grier (1971)
      A' values from .9 to 1.0.

PMID- 18823419
TI  - Perceiving age and gender in unfamiliar faces: brain potential evidence for
      implicit and explicit person categorization.
AB  - We used repetition priming to investigate implicit and explicit processes of
      unfamiliar face categorization. During prime and test phases, participants
      categorized unfamiliar faces according to either age or gender. Faces presented
      at test were either new or primed in a task-congruent (same task during priming
      and test) or incongruent (different tasks) condition. During age categorization,
      reaction times revealed significant priming for both priming conditions, and
      event-related potentials yielded an increased N170 over the left hemisphere as a
      result of priming. During gender categorization, congruent faces elicited priming
      and a latency decrease in the right N170. Accordingly, information about age is
      extracted irrespective of processing demands, and priming facilitates the
      extraction of feature information reflected in the left N170 effect. By contrast,
      priming of gender categorization may depend on whether the task at initial
      presentation requires configural processing.

PMID- 18823421
TI  - Modality-specific attentional startle modulation during continuous performance
      tasks: a brief time is sufficient.
AB  - Attentional startle modulation has been found to be modality specific in
      continuous performance tasks (CPTs) and modality nonspecific in trial-structured
      tasks. Experiment 1 investigated whether attentional blink modulation in a CPT
      would change if a trial structure was imposed. Participants performed a visual
      CPT either continuously (CONT), or during brief periods of time signaled by a
      change in screen color with stimuli either presented all the time (MIXED) or only
      during the trial segments (DISC). Contrary to expectation, evidence for modality
      specific attentional startle modulation-smaller acoustic startle during targets
      than during nontargets-was strongest in Groups MIXED and DISC. Experiment 2
      confirmed that this pattern of results was present during the first stimulus of
      the task period in group DISC. This suggests that the continuous nature of a task
      is not critical in determining the attentional mechanisms engaged.

PMID- 18823420
TI  - Psychiatric and neurophysiological predictors of obesity in HIV/AIDS.
AB  - The objective of the study was to identify predictors of obesity. One hundred
      eleven nonobese and 48 obese HIV-1 seropositive patients provided information on
      medical history and other characteristics. They were then asked to detect the
      passage of 2-s time intervals while the contingent negative variation (CNV) was
      recorded. Obese patients were healthier, more likely to be receiving Highly
      Active Antiretroviral Therapy, and less likely to be substance dependent. Obese
      patients also exhibited a greater CNV slope and responded prematurely. A path
      model suggested that CD4+count and protease inhibitor use directly predicted
      obesity. Depression had no direct effect. However, when incorporated into a
      hypothetical construct, "mood dysregulation," that also included childhood
      conduct problems and stimulant dependence, the shared variance among the
      indicators did predict obesity. This relationship was mediated through premature
      response preparation (anterior scalp CNV amplitude) and its hypothesized
      association with impatience/impulsivity.

PMID- 18823422
TI  - Associations between the perception of dyspnea, pain, and negative affect.
AB  - The perception of dyspnea shares many characteristics with the perception of
      pain, and both sensations might be linked to affective states. Therefore, the
      present study investigated the associations between perceived dyspnea, pain, and
      negative affect during resistive load breathing, the cold-pressor test, and
      affective picture viewing in healthy volunteers. Physiological and psychological
      measures confirmed successful experimental manipulation. There was a positive
      correlation between perceived dyspnea and pain in the unpleasantness dimension,
      but not in the intensity dimension, and this was further related to negative
      affect. These associations might be explained by similarities in the cortical
      processing of dyspnea, pain, and negative affect. The present findings extend the
      knowledge on similarities between dyspnea and pain and provide support for
      theories focusing on the perception of physiologic sensations in the development
      of affective states.

PMID- 18823423
TI  - The case of letter rhyming: an ERP study.
AB  - Previous visual event-related potential (ERP) studies using prime-target pairs of
      word and pseudoword stimuli have reported a robust rhyming effect such that
      nonrhyming targets elicit a larger N450 than rhyming targets. However, results of
      similar studies using simpler linguistic stimuli-single letters-are equivocal. We
      used lowercase and uppercase letter pairs in a simple ERP prime-target rhyming
      paradigm to further investigate whether single letters could elicit the typical
      rhyming effect and, if so, whether the rhyming effect was sensitive to physical
      orthography (which differed between the case conditions). The typical N450
      rhyming effect was observed in both the lowercase and uppercase letter pair
      conditions, with similar amplitude and latency between conditions. This pattern
      of results suggests that the N450 rhyming effect is not sensitive to physical
      (case) orthography and likely primarily indexes phonological processing related
      to the rhyme task.

PMID- 18823424
TI  - Cardiac vagal activity during psychological stress varies with social functioning
      in older women.
AB  - The polyvagal theory states that social behavior is linked to cardiac vagal
      control. This theory has been tested widely in infants and children, but less so
      in adults. Thus, we examined if resting or stress-related changes in high
      frequency heart rate variability (HF-HRV; a presumed index of vagal control)
      varied with social functioning in 50 healthy women (mean age 68 years). After
      completing assessments of social functioning, women were exposed to laboratory
      stressors with concurrent psychophysiological monitoring. Although stressor
      induced suppression of HF-HRV was common, women with less stressor-induced
      suppression of HF-HRV reported more positive social functioning. Resting HF-HRV
      was not related to social functioning. These findings are at apparent odds with
      the polyvagal theory; however, they complement prior work suggesting that
      emotional self-regulation could plausibly modulate cardiac vagal control in
      association with social functioning.

PMID- 18823425
TI  - Neural activity and diurnal variation of cortisol: evidence from brain electrical
      tomography analysis and relevance to anhedonia.
AB  - The medial prefrontal cortex (mPFC), hippocampus, and amygdala are implicated in
      the regulation of affect and physiological processes, including hypothalamic
      pituitary-adrenal (HPA) axis function. Anhedonia is likely associated with
      dysregulation of these processes. Dense-array resting electroencephalographic and
      cortisol were obtained from healthy and anhedonic groups. Low-resolution
      electromagnetic tomography was used to compute intracerebral current density. For
      the control group, voxelwise analyses found a relationship between current
      density in beta and gamma bands and steeper cortisol slope (indicative of more
      adaptive HPA axis functioning) in regions of the hippocampus, parahippocampal
      gyrus, and mPFC. For the anhedonic group, the mPFC finding was absent. Anhedonia
      may be characterized by disruptions of mPFC-mediated neuroendocrine regulation,
      which could constitute a vulnerability to the development of stress-related
      disorders.

PMID- 18823426
TI  - RUN/EDIT information processing mode and phasic cardiac acceleration.
AB  - Our previous research showed that tasks demanding running of ready-to-use
      programs (RUN tasks) caused a greater tonic heart rate increase than did tasks
      that require problem solving (EDIT tasks). We found also a similar though not so
      consistent effect in the analysis of phasic cardiac acceleration. The aim of the
      present study was to replicate the last finding using new experimental tasks.
      Fifty-four male secondary school pupils were divided randomly into three
      experimental groups. Each group performed a different version of a nonsignaled
      reaction time (RT) task: simple RT, sensory choice RT, and semantic choice RT.
      Participants had to respond within an established time limit, but this limit was
      continuously modified in such a way that each participant was given positive
      feedback in approximately 50% of trials. According to expectations, the simple RT
      task evoked greater phasic cardiac acceleration than did the choice RT tasks.

PMID- 18823427
TI  - Schizophrenia diagnosis and anterior hippocampal volume make separate
      contributions to sensory gating.
AB  - Impaired P50 gating is thought to reflect a core deficit in schizophrenia, but
      the relevant neural network is not well understood. The present study used EEG
      and MEG to assess sensory gating and volumetric MRI to measure hippocampal volume
      to investigate relationships between them in 22 normal controls and 22 patients
      with schizophrenia. In the schizophrenia group, anterior but not posterior
      hippocampal volume was smaller, and both the P50 and M50 gating ratios were
      larger (worse) than in controls. Independent of group, left-hemisphere M50 gating
      ratio correlated negatively with left anterior hippocampal volume, and right
      hemisphere M50 gating ratio correlated negatively with right anterior hippocampal
      volume. Schizophrenia diagnosis predicted M50 gating independent of hippocampal
      volume. These results are consistent with the finding that hippocampus is a
      critical part of a fronto-temporal circuit involved in auditory gating.

PMID- 18823428
TI  - Assessing sleepiness in the rat: a multiple sleep latencies test compared to
      polysomnographic measures of sleepiness.
AB  - Sleepiness following 6 h of sleep deprivation (SD) was evaluated with a rat
      multiple sleep latencies test (rMSLT), and the findings were compared to
      conventional polysomnographic measures of sleepiness. The 6 h of SD was produced
      by automated activity wheels, and was terminated at either the end of the light
      period or at the beginning of the dark period. The rMSLT consisted of 5 min
      wakefulness induced by sensory stimulation followed by 25 min of freedom to
      sleep. This procedure was repeated every 30 min for 3 h and was designed to
      minimize the amount of sleep lost due to the testing procedure. In separate rats,
      6 h SD was followed by undisturbed recovery, allowing evaluation of conventional
      polysomnographic measures of sleepiness. Sleep onset latencies were reduced
      following SD, with recovery in the light (baseline = 8 min, 3 s versus post-SD =
      1 min, 17 s) and dark period (baseline = 14 min, 17 s versus 7 min, 7 s). Sleep
      onset latencies were not altered by varying the duration criterion for the first
      sleep bout (i.e., sleep bout length criteria of 10, 20, 30, or 60 s were
      compared). Polysomnographic variables (non-rapid eye movement sleep episode
      duration, delta power, and number of awakenings) also provided reliable indirect
      measures of sleepiness, regardless of whether the recovery sleep occurred in the
      light or dark period. Evaluation of effect size indicated that the rMSLT was a
      strong measure of sleepiness, and was influenced by homeostatic, circadian, and
      illumination factors. The rMSLT provided a simple, objective, robust and direct
      measure of sleepiness that was as effective as conventional polysomnographic
      measures of sleepiness.

PMID- 18823429
TI  - Helicobacter pylori eradication may induce de novo, but transient and mild,
      reflux esophagitis: Prospective endoscopic evaluation.
AB  - BACKGROUNDS AND AIM: The effect on reflux esophagitis of eradicating Helicobacter
      pylori is variable and not fully defined. We previously reported that in patients
      who have reflux esophagitis associated with duodenal ulcer, a significant
      improvement in the pre-existing reflux esophagitis occurred after H. pylori was
      eradicated. In the present study, we asked whether H. pylori eradication leads to
      de novo development of reflux esophagitis in peptic ulcer patients. METHODS:
      Prospective post-eradication evaluations were conducted in 1195 H. pylori
      positive patients with peptic ulcer diseases who were confirmed not to have
      reflux esophagitis by endoscopic examination before eradication therapy. After
      eradication therapy, endoscopy and a urea breath test were performed yearly.
      RESULTS: A total of 1187 patients were followed for up to 10.0 years (a mean of
      3.6 years). Reflux esophagitis developed in 279 of 1000 patients cured of
      infection and in 26 of 187 patients who had persistent infection (P < 0.0001,
      Fisher's exact test). The esophagitis was mild (Los Angeles grade A) in most
      patients, transient in approximately one-half, and rarely necessitated long-term
      medication for the condition. Cure of infection, alcohol consumption, younger
      age, and high body mass index were identified as significant factors for the risk
      of developing non-transient reflux esophagitis. CONCLUSIONS: Cure of H. pylori
      infection may increase the risk of developing reflux esophagitis in patients with
      peptic ulcer, but the esophagitis is mostly mild and transient, and long-term
      medication is rarely required. Thus, H. pylori eradication therapy need not be
      withheld for fear of provoking reflux esophagitis.

PMID- 18823430
TI  - Effects of CYP2C19 and MDR1 genotype on the eradication rate of Helicobacter
      pylori infection by triple therapy with pantoprazole, amoxycillin and
      clarithromycin.
AB  - BACKGROUND: CYP2C19 polymorphism plays an important role in the metabolism of
      proton pump inhibitors. The multidrug resistance (MDR)1 genotype is associated
      with the successful eradication of Helicobacter pylori. The aim of the present
      study was to investigate the effects of CYP2C19 and MDR1 genotypes on the
      eradication rate of H. pylori using a pantoprazole-based triple therapy. METHODS:
      A total of 210 patients infected with H. pylori were treated with 40 mg
      pantoprazole, 500 mg clarithromycin and 1000 mg amoxicillin twice daily for 7
      days. The CYP2C19 genotype was determined with polymerase chain reaction (PCR)
      restriction fragment length polymorphism analysis. The MDR1 C3435T polymorphism
      was identified by PCR-based allele-specific amplification (PCR-ASA). RESULTS: Of
      the 210 patients who completed the study, 174 (82.9%, 95.0% confidence interval
      [CI], 77.8-88.0%) achieved successful eradication after the first cycle of
      therapy. The eradication rates for H. pylori were 86.7%, 81.1% and 82.1% in the
      homozygous extensive, heterozygous extensive and poor metabolizer groups,
      respectively (P = 0.65). Moreover, the cure rates in the CC, CT, and TT groups
      were 82.7%, 84.4% and 76.9%, respectively (P = 0.66). Multiple logistic
      regression analysis revealed that endoscopic diagnosis was a significant
      independent risk factor for treatment failure. CONCLUSION: The eradication rates
      of H. pylori by pantoprazole, amoxicillin and clarithromycin were not
      significantly different among the CYP2C19 and MDR1 genotypes. Hence, the cure
      rate of H. pylori in the Korean population was no different for the CYP2C19 and
      MDR1 genotypes.

PMID- 18823431
TI  - Multi-center survey regarding the management of anticoagulation and antiplatelet
      therapy for endoscopic procedures in Japan.
AB  - BACKGROUND: A guideline on the management of anticoagulation and antiplatelet
      therapy for endoscopic procedures has been established from Japan
      Gastroenterological Endoscopy Society in 2005. However, it is unknown whether
      consensus on the management of these conditions is obtained among endoscopists in
      daily practice owing to the guideline. METHODS: To study the current practice on
      the management, survey questionnaires were sent to 13 representative endoscopists
      of 13 middle or high-volume hospitals in the Tokyo area. RESULTS: Responses were
      obtained from all 13 endoscopists. The results showed that only five (38%) and
      six (46%) hospitals had their own standard protocols regarding the management for
      endoscopic biopsy and endoscopic mucosal resection (EMR), respectively. There was
      a wide variation among endoscopists in terms of discontinuation of each agent.
      When the patients had a major risk of thromboembolism due to discontinuation of
      anticoagulants and antiplatelet agents, seven (54%) and five (38%) endoscopists,
      respectively, never took a biopsy. Similar numbers of endoscopists never carried
      out EMR. During discontinuation of anticoagulants or antiplatelet agents for
      biopsy and EMR, three (23%) and three (23%) endoscopists, respectively,
      experienced patients with thromboembolic events. CONCLUSIONS: There is still a
      wide variation and confusion among endoscopists after establishment of our
      national guideline. A robust national guideline with clearer description based on
      the scientific evidence is needed.

PMID- 18823432
TI  - Views of supervisors of colonoscopy training on quality issues for the national
      bowel cancer screening program in Australia.
AB  - BACKGROUND AND AIM: To describe the views of supervisors of colonoscopy training
      in regard to colonoscopy training capacity and quality in Australia. METHODS:
      Anonymous postal surveys from March to May 2007 were posted to 127 colonoscopy
      training supervisors (30.2% estimated response rate). The surveys queried
      colonoscopy training capacity and quality, supervisors' views and opinions on
      innovative approaches to colonoscopy training, number of colonoscopies and time
      required by trainees to gain competence in colonoscopy. RESULTS: Approximately
      50% of trainers agreed and 27% disagreed that current numbers of training places
      were adequate to maintain a skilled colonoscopy workforce in preparation for the
      National Bowel Cancer Screening Program (NBCSP). A collaborative approach with
      the private sector was seen as beneficial by 65%. Non-gastroenterologists (non
      GEs) were more likely than gastroenterologists (GEs) to be of the opinion that
      simulators are beneficial for colonoscopy training (chi(2)-test = 5.55, P =
      0.026). The majority of trainers did not support training either nurses (73%) or
      general practitioners (GPs) in colonoscopy (71%). Approximately 60% of trainers
      considered that the current requirements for recognition of training in
      colonoscopy could be insufficient for trainees to gain competence and 80% of
      those indicated that > or = 200 colonoscopies were needed. CONCLUSIONS:
      Colonoscopy training in Australia has traditionally followed the apprenticeship
      model. Projected increases in demand for colonoscopy with the introduction of the
      NBCSP may require additional training places and new and innovative approaches to
      training in order to ensure the provision of high-quality colonoscopy services
      under the NBCSP.

PMID- 18823433
TI  - Cutaneous gastric electrical stimulation alters gastric motility in dogs: New
      option for gastric electrical stimulation?
AB  - BACKGROUND AND AIM: We investigated the effects of cutaneous gastric electrical
      stimulation (CGES) on gastric myoelectrical activity, postprandial antral
      contractions and gastric tone in dogs. METHODS: CGES was carried out via
      abdominal surface electrodes over the stomach. After an overnight fast, gastric
      slow waves were recorded from the serosal electrodes in six dogs at a frequency
      of 4.4 cycles/min (c.p.m.) or 10 c.p.m. Nine dogs were used for the measurement
      of postprandial antral contractions. Gastric tone at baseline and during CGES was
      measured in six of the dogs. RESULTS: We found that: (i) CGES at 4.4 c.p.m.
      decreased slow wave frequency (5.1 vs 4.6 c.p.m., P < 0.05) and increased slow
      wave power (-6.2 vs 2.7 c.p.m., P < 0.05); CGES at 10 c.p.m. increased slow wave
      frequency (5.1 vs 9.2 dB, P < 0.05) and decreased normal slow waves (85.4% vs
      60.0%, P < 0.05); (ii) CGES at 10 c.p.m. significantly suppressed postprandial
      antral contractions (P < 0.01); (iii) CGES had no effects on gastric tone.
      CONCLUSIONS: CGES is capable of altering gastric slow waves and inhibiting
      gastric motility. It may have therapeutic potential for treating eating
      disorders, such as obesity. However, clinical studies are needed to explore the
      potential of CGES.

PMID- 18823434
TI  - Biliary phenotype of hepatocellular carcinoma after preoperative transcatheter
      arterial chemoembolization.
AB  - BACKGROUND AND AIM: Transcatheter arterial chemoembolization (TACE) is now the
      mainstay of treatment for non-curative hepatocellular carcinoma (HCC), and hoped
      to have chemotherapeutic and ischemic effects; however, the histopathological
      changes of HCC caused by TACE have not been sufficiently discussed so far. We
      aimed to assess the morphological and immunohistochemical features of HCC treated
      with TACE by immunostaining cytokeratin (CK) 7, CK14, CK19 and vimentin, and to
      correlate these data with observed clinicopathological characteristics. METHODS:
      Eighty cases of surgically resected HCC with preoperative TACE and 146 cases of
      HCC resected without TACE as a control were analyzed. RESULTS: The incidences of
      intrahepatic metastasis, poorly differentiated histology, multinucleated giant
      cells, mitotic figures and cytoplasmic inclusion bodies in the TACE group were
      significantly higher than those in the non-TACE group. The TACE group showed
      reactivity for CK7 in 56.3% (45/80) of patients, CK14 in 12.5% (10/80), CK19 in
      23.8% (19/80) and vimentin in 6.3% (5/80) of patients. CK19 expression in the
      TACE group was significantly higher than in the non-TACE group (P = 0.0423).
      There was no correlation between immunoreactivity and the number of times TACE
      was carried out, but the expression of CK19 and vimentin in the massive necrotic
      group was higher than that in the mild necrotic group (P = 0.0197, P = 0.0229,
      respectively). Only TACE was an independent determinant of CK19 expression in all
      cases by multivariate analysis. CONCLUSIONS: These results suggest that
      preoperative TACE may have an impact on the biliary phenotype of HCC. Some post
      therapeutic HCC patients might develop HCC with a biliary phenotype indicating
      more aggressive malignancies.

PMID- 18823435
TI  - Clinical, biochemical, immunological and virological profiles of, and
      differential diagnosis between, patients with acute hepatitis B and chronic
      hepatitis B with acute flare.
AB  - BACKGROUND AND AIM: In areas with high or intermediate endemicity for chronic
      hepatitis B virus (HBV) infection, it is difficult to distinguish acute hepatitis
      B (AHB) from chronic hepatitis B with an acute flare (CHB-AF) in patients whose
      prior history of HBV infection has been unknown. The present study aimed to
      screen laboratory parameters other than immunoglobulin M antibody to hepatitis B
      core antigen (IgM anti-HBc) to discriminate between the two conditions. METHODS:
      A retrospective and prospective study was conducted in patients first presenting
      clinically as HBV-related acute hepatitis to sort out acute self-limited
      hepatitis B (ASL-HB). Then, clinical and laboratory profiles were compared
      between patients with ASL-HB and CHB-AF. Parameters closely associated with ASL
      HB were chosen to evaluate sensitivity, specificity, accuracy, positive
      predictive values and negative predictive values for diagnosing AHB. RESULTS:
      There were significant differences between patients with ASL-HB and CHB-AF in
      relation to clinical and laboratory aspects, with many outstanding differences in
      levels of serum HBV-DNA, hepatitis B e antigen (HBeAg) and alpha-fetoprotein
      (AFP) as well as IgM anti-HBc. In particular, there was a greater difference
      between the two groups in low levels of HBeAg (ratio of the optical density of
      the sample to the cut-off value [S/CO] <20) than in negativity for HBeAg (42.7%
      and 13.5% vs 49.3% and 45.9%). 1:10 000 IgM anti-HBc had a sensitivity and
      specificity of 96.2% and 93.1%, respectively, for predicting ASL-HB. Combining it
      with AFP, HBeAg or HBV-DNA could improve diagnostic power. A combination of IgM
      anti-HBc, HBV-DNA and HBeAg had a predictive value of 98.9% and a negative
      predictive value of 100.0%, similar to that of a combination of IgM anti-HBc and
      HBV-DNA. Adding AFP to the combinations of IgM anti-HBc and HBV-DNA or HBeAg
      could further heighten the positive predictive value. The positive predictive
      value and negative predictive value of the combination of IgM anti-HBc, HBV-DNA
      and AFP were both 100.0%. CONCLUSIONS: (i) There are significant differences with
      respect to clinical, biochemical, immunological and virological aspects between
      ASL-HB and CHB-AF. (ii) Of several diagnostic combinations, IgM anti-HBc jointing
      HBV-DNA is most effective and most practicable in distinguishing ASL-HB from CHB
      AF. (iii) A low HBeAg level is more useful than negative HBeAg in differential
      diagnosis between ASL-HB and CHB-AF. (iv) In those patients with a high level of
      IgM anti-HBc, serum AFP level >10x upper reference limit could rule out a
      probability of ASL-HB.

PMID- 18823436
TI  - Anti-gastric cancer effects of celecoxib, a selective COX-2 inhibitor, through
      inhibition of Akt signaling.
AB  - BACKGROUND AND AIM: Previously, we showed that treatment with celecoxib
      significantly reduced the number of viable gastric cancer cells, in a dose- and
      time-dependent manner. However, the specific anti-cancer effects of celecoxib on
      gastric cancer cells have not been clarified. The present in vitro study was
      carried out to investigate the mechanism involved in the anti-gastric cancer
      effects of celecoxib. METHODS: 3-(4,5-Dimethyl-2 thiazoyl)-2,5-diphenyl-2H
      tetrazolium bromide (MTT) assay was carried out after treating AGS cells (human
      gastric cancer cell line, ATCC CRL 1739) with celecoxib or indomethacin, and the
      effect of prostaglandin E(2) or LY294002 (PI3K inhibitor) was evaluated. Western
      blot analysis of tAkt (total Akt), pAkt (phosphorylated Akt), pGSK3beta
      (phosphorylated glycogen synthase kinase-3beta), pFKHR (phosphorylated forkhead
      transcriptional factor), and caspase-9 was carried out at various concentrations
      (0, 5, 10, 25, or 50 micromol/L) of celecoxib or indomethacin-treatment for 24 or
      48 h in AGS cells. RESULTS: Celecoxib- or LY294002-induced cell death was found
      to occur in a dose-dependent manner in AGS cells, and these decreases were
      slightly recovered by the addition of PGE(2) (25 or 50 micromol/L). The
      expression of pAkt but not tAkt was lower in the celecoxib treated-AGS cells and
      the response was dose dependent (P < 0.05). The expression of pGSK3beta and pFKHR
      was also significantly decreased in the celecoxib treated-AGS cells. Procaspase 9
      (47 kDa) was frequently cleaved into 37, 35 and 17 kDa fragments in the celecoxib
      treatment group. However, these changes in cell signal transduction were not
      observed in the indomethacin treated-AGS cells. CONCLUSION: The anti-cancer
      effects of celecoxib on gastric cancer cells might be partly mediated by
      downregulation of Akt, GSK3beta, FKHR, and upregulation of caspase-9, in the
      mitochondrial apoptotic pathway.

PMID- 18823437
TI  - Dietary trans-resveratrol bioavailability and effect on CCl4-induced liver lipid
      peroxidation.
AB  - BACKGROUND AND AIM: Several in vitro studies have demonstrated the ability of
      pure trans-resveratrol (t-Res) to act as an anti-oxidant, but the scientific
      literature is lacking in in vivo studies dealing with dietary t-Res
      bioavailability in oxidative stress models. Our aim was to investigate the
      bioavailability of t-Res from dietary sources and its effect on an animal model
      of carbon tetrachloride (CCl4)-induced liver lipid peroxidation. METHODS: Ten
      rats were intragastrically administered for 14 days with a grape-stalk extract
      determining a daily t-Res dosage of 3 mg/kg. The control group (10 rats) was
      daily injected with the vehicle solvent without the t-Res extract. After 1 week,
      the induction of liver lipid peroxidation by CCl4 injection was carried out.
      Serum and liver samples, at different time intervals, were collected to evaluate
      t-Res content, by high-performance liquid chromatography (HPLC) and liquid
      chromatography-mass spectometry-mass spectometry (LC-MS-MS). Liver
      malondialdehyde (MDA) as marker of oxidative stress was measured. RESULTS: t-Res
      accumulates in the liver reaching 49.8 +/- 10.2 ng/g after 7 days and 191.8 +/-
      15.3 ng/g after 14 days. No t-Res was detected in serum. The increase of MDA
      liver concentration due to CCl4 injection after 24 h and 1 week was reduced by
      38% and a 63%, respectively, by the treatment with the t-Res extract.
      CONCLUSIONS: A moderate consumption of t-Res from a dietary source resulted in a
      time-dose-dependent liver accumulation. It was able to counteract in vivo CCl4
      induced liver lipid peroxidation thus demonstrating the hepatoprotective property
      of t-Res.

PMID- 18823438
TI  - Marked elevation of serum mitochondrion-derived markers in mild models of non
      alcoholic steatohepatitis in rats.
AB  - BACKGROUND AND AIM: In order to find sensitive serum markers in non-alcoholic
      steatohepatitis, liver-specific injury markers were thoroughly examined in mild
      models of NASH in rats. METHODS: Wistar and Sprague-Dawley rats were fed a
      choline-deficient diet for 4 weeks, and serum activities of liver-specific enzyme
      markers were examined. In the drug-induced steatohepatitis model, tetracycline
      (0.4 mmol/kg) was given i.p. to rats and the course of hepatotoxicity was
      evaluated with serum markers, together with the accumulation of total lipid and
      thiobarbituric acid-reactive substances in the liver. RESULTS: In Wistar rats,
      serum activities of most enzymes tested were significantly increased. In Sprague
      Dawley rats, in contrast, the serum level of ornithine carbamyltransferase and
      glutamate dehydrogenase were markedly elevated in the choline-deficient diet
      group compared with the control diet groups, whereas other markers were not
      significantly increased. In the tetracycline-induced steatohepatitis model, the
      extent of the increase was much higher in mitochondrial markers and the peak of
      the increase in these markers corresponded with the increase of hepatic total
      lipid and thiobarbituric acid-reactive substance. CONCLUSIONS: These observations
      show that serum mitochondrial enzyme markers are potent markers for non-alcoholic
      steatohepatitis in rats and are possibly applicable to humans.

PMID- 18823439
TI  - Comparison of therapeutic effects between radiofrequency ablation and
      percutaneous microwave coagulation therapy for small hepatocellular carcinomas.
AB  - BACKGROUND: Although thermal ablation therapies have gained fairly wide
      acceptance as an effective treatment for small hepatocellular carcinoma (HCC),
      there have been only a few clinical studies comparing the response to
      radiofrequency ablation (RFA) and percutaneous microwave coagulation therapy
      (PMCT). We evaluated the therapeutic efficacy and safety of these two procedures
      for the treatment of small HCC measuring < or = 2 cm in diameter. METHODS: Thirty
      four patients who had 37 nodules were treated by RFA and were compared with 49
      patients (56 nodules) who underwent PMCT. Treatment was repeated until complete
      tumor necrosis was confirmed by contrast computed tomography (CT) scanning. The
      therapeutic efficacy and complications were retrospectively compared between the
      two procedures. RESULTS: (i) There were significantly fewer treatment sessions (P
      < 0.001) in the RFA group than in the PMCT group, but the necrotic area was
      significantly larger (P < 0.001) in the former group. (ii) The local recurrence
      rate was significantly lower (P = 0.031) after RFA than after PMCT, although the
      ectopic recurrence rate showed no significant difference. (iii) The cumulative
      survival rate was significantly higher (P = 0.018) after RFA than after PMCT.
      (iv) The incidence of pain and fever after treatment was significantly higher in
      the PMCT group. Bile duct injury, pleural effusion, and ascites were also
      significantly more common in the PMCT group. CONCLUSIONS: RFA is more useful than
      PMCT for the treatment of small HCC because it is minimally invasive and achieves
      a low local recurrence rate, high survival rate, and extensive necrosis after
      only a few treatment sessions.

PMID- 18823440
TI  - Granulocytapheresis versus methylprednisolone in patients with acute ulcerative
      colitis: 12-month follow up.
AB  - AIM: To evaluate granulocytapheresis (GCAP) in active ulcerative colitis (UC),
      with particular attention to the long-term effects of such treatment. METHODS: We
      included 80 patients with UC. Activity of the disease was evaluated by clinical
      activity index and endoscopic index. Patients were randomly divided in two
      groups: Group A received a five-session (1 session/week) treatment with GCAP,
      Group B were treated with i.v. or i.m. methylprednisolone (MP). Concomitant
      therapy with oral 5-aminosalicylic acid (5-ASA) 2.4 g/day was maintained in both
      groups. Subjects who achieved a remission were clinically and endoscopically
      followed for 12 months after the end of GCAP or MP. RESULTS: Remission was
      observed in 72.5% of those treated with GCAP versus 50% of those treated with MP.
      After a 12-month follow up, a sustained remission was recorded in 40% of those
      treated with GCAP and in 25% of those treated with MP. During the GCAP only a
      transient mild headache was recorded in 10% of patients, whereas side-effects
      were observed in 50% of those treated with MP (P < 0.05). CONCLUSION: GCAP
      results were superior to MP for the treatment of UC, even though no statistically
      significant difference was observed. Side-effects in the GCAP group were
      significantly lower than in the MP group. This new therapeutic approach seems
      able to maintain the condition of remission for a longer time after a flare. In
      fact, the patients who had obtained a remission after a course of CGAP showed
      fewer relapses during the follow up compared to the patients treated with MP.

PMID- 18823441
TI  - Model to predict rebleeding following endoscopic therapy for non-variceal upper
      gastrointestinal hemorrhage.
AB  - BACKGROUND AND AIM: Following endoscopic therapy, up to 20% of patients with non
      variceal upper gastrointestinal hemorrhage experience rebleeding. The aim of the
      present study was to determine risk factors for recurrent hemorrhage in these
      patients. METHODS: This was a retrospective cohort study of consecutive patients
      admitted to a tertiary care hospital between 1 July 1999 and 30 June 2004, with
      non-variceal upper gastrointestinal hemorrhage. Patients were evaluated for
      rebleeding within 30 days of successful therapeutic endoscopy. Using the
      hospital's endoscopic database, 236 patients were identified. Risk factors were
      identified using multivariable logistic regression with backward selection.
      Internal validation was carried out using bootstrapping. RESULTS: Six risk
      factors were identified: failure to use a proton pump inhibitor post-procedure (P
      = 0.056), Endoscopically demonstrated bleeding (P = 0.053), peptic ulcer as the
      bleeding source (P = 0.018), treatment with epinephrine monotherapy (P = 0.0026),
      post-procedure intravenous or low molecular weight heparin use (P = 0.0014), and
      moderate or severe cirrhosis (P = 0.032) (PEPTIC). The risk of rebleeding
      increased as the number of risk factors present increased. The observed rates of
      rebleeding were: 7.1%, 16.4%, 37.0%, 75.0% and 100% for zero, one, two, three or
      four risk factors, respectively (no patients had five or six risk factors
      present). The bias-adjusted area under the receiver-operator characteristic curve
      for the number of risk factors predicting rebleeding was 0.69. CONCLUSIONS: We
      have identified six easily remembered risk factors, which, when summed, predict
      recurrent hemorrhage following endoscopic therapy for non-variceal upper
      gastrointestinal hemorrhage.

PMID- 18823442
TI  - L-Ornithine-l-aspartate in the management of hepatic encephalopathy: a meta
      analysis.
AB  - BACKGROUND AND AIM: Hepatic encephalopathy continues to be a major clinical
      problem and the current decade has not witnessed major therapeutic breakthroughs
      in this area. L-ornithine-l-aspartate (LOLA) is not frequently used as there are
      still some reservations about its benefits. The present study aimed to assess the
      effectiveness and safety of LOLA in the management of hepatic encephalopathy.
      METHODS: We used the method recommended by the Cochrane Collaboration to perform
      a meta-analysis of randomized controlled trials of LOLA therapy for hepatic
      encephalopathy including three randomized controlled trials. RESULTS: Three
      randomized trials randomizing 212 patients were included. LOLA versus placebo had
      a significant effect on improvement of hepatic encephalopathy (relative risk
      1.89; 95% CI 1.32 to 2.71; P = 0.0005). This comparison showed no statistical
      heterogeneity (P = 0.85 and chi(2) = 0.09). Subgroup analysis showed that LOLA
      could be effective versus placebo in trials with grade I or II overt hepatic
      encephalopathy patients (relative risk 1.87; 95% CI 1.30 to 2.68; P = 0.0007) and
      had no significant effect in trials with subclinical hepatic encephalopathy
      patients (relative risk 1.69; 95% CI 0.72 to 3.94; P = 0.23). Adverse effects
      were observed in only three patients treated with LOLA in one report.
      CONCLUSIONS: LOLA benefited patients with overt hepatic encephalopathy (I or II),
      whereas these data do not support the use of LOLA for patients with subclinical
      hepatic encephalopathy.

PMID- 18823443
TI  - Surface enhanced laser desorption/ionization profiling: New diagnostic method of
      HBV-related hepatocellular carcinoma.
AB  - BACKGROUND AND AIM: To screen for serum biomarkers of HBV-related hepatocellular
      carcinoma (HCC) and HBV-related liver cirrhosis (LC) in an attempt to seek a new
      method for differential diagnosis of HCC and LC using surface-enhanced laser
      desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) techniques.
      METHODS: Using SELDI-TOF-MS, serum proteins/peptide profiles on the immobilized
      metal ion affinity capture (IMAC) protein chips were obtained from 29 HCC
      patients and 30 LC patients. Discriminant analysis was carried out to establish
      new diagnostic methods using protein/peptide peaks with or without alpha
      fetoprotein (AFP). RESULTS: Forty-five protein/peptide peaks changed much more in
      the HCC group than they did in the LC group. Discriminant analysis using the
      Wilcoxon rank-sum test showed high sensitivity and specificity in distinguishing
      HCC from LC. The most significantly differentiating peak, 3892, offered 69.0%
      sensitivity, 83.3% specificity and 80% positive predictive value in
      distinguishing HCC and LC. Interestingly, six HCC patients with negative serum
      AFP were confirmed by peak 3892. The combination of multi-protein peaks (m/z =
      9297, 29 941) with AFP offered an 82.8% sensitivity, 93.3% specificity and 92.3%
      positive predictive value, which was much better than AFP alone (P = 0.013).
      CONCLUSIONS: Special proteins/peptides of serum may differentiate HBV-related HCC
      and HBV-related LC, indicating that SELDI-TOF-MS may be useful to distinguish HCC
      from LC with the proper discriminant analytical method. SELDI peak 3892 may be a
      complementary diagnostic marker to positive AFP for HCC and a potential marker
      for the diagnosis of AFP-negative HCC as well.

PMID- 18823444
TI  - Wounding-mediated gene expression and accelerated viviparous reproduction of the
      pea aphid Acyrthosiphon pisum.
AB  - Most insects mount a potent antimicrobial defence upon contact with microbes or
      microbe-associated pattern molecules. Using a combined set of methods for
      analysis of insect innate immunity, we report here that piercing of the pea aphid
      Acyrthosiphon pisum with a bacteria-contaminated needle elicits lysozyme-like
      activity in the haemolymph but no detectable activities against live bacteria.
      Confirming these results, we found no homologues of known antimicrobial peptides
      in our cDNA library generated by using the suppression subtractive hybridization
      method or in over 90,000 public expressed sequence tag (EST) sequences, but
      lysozyme genes have recently been described in A. pisum. Interestingly, we
      discovered that production of viviparous offspring was significantly accelerated
      upon wounding. Therefore, we postulate that aphids may increase terminal
      reproductive investment and limit antibacterial defence in response to a threat
      to their survival.

PMID- 18823445
TI  - Development of an interactive computer program for advance care planning.
AB  - OBJECTIVE: To describe the development of an innovative, multi-media decision aid
      for advance care planning. BACKGROUND: Advance care planning is an important way
      for people to articulate their wishes for medical care when they are not able to
      speak for themselves. Living wills and other types of advance directives are the
      most commonly used tools for advance care planning, but have been criticized for
      being vague, difficult to interpret, and inconsistent with individuals' core
      beliefs and values. RESULTS: We developed a multimedia, computer-based decision
      aid for advance care planning ('Making Your Wishes Known: Planning Your Medical
      Future') to overcome many of the limitations of standard advance directive forms.
      This computer program guides individuals through the process of advance care
      planning, and unlike standard advance directives, provides tailored education,
      values clarification exercises, and a decision-making tool that translates an
      individual's values and preferences into a specific medical plan that can be
      implemented by a health-care team. Pilot testing with 50 adult volunteers
      recruited from an outpatient primary care clinic showed high levels of
      satisfaction with the program. Further pilot testing with 34 cancer patients
      indicated that the program was perceived to be highly accurate at representing
      patients' wishes. CONCLUSIONS: This paper describes the development of an
      innovative decision aid for advance care planning that was designed to overcome
      common problems with standard advance directives. Preliminary testing suggests
      that it is acceptable to users and is accurate.

PMID- 18823446
TI  - Advancing measurement of patient safety culture.
AB  - OBJECTIVE: To examine the psychometric and unit of analysis/strength of culture
      issues in patient safety culture (PSC) measurement. DATA SOURCE: Two cross
      sectional surveys of health care staff in 10 Canadian health care organizations
      totaling 11,586 respondents. STUDY DESIGN: A cross-validation study of a measure
      of PSC using survey data gathered using the Modified Stanford PSC survey (MSI
      2005 and MSI-2006); a within-group agreement analysis of MSI-2006 data.
      Extraction Methods. Exploratory factor analyses (EFA) of the MSI-05 survey data
      and confirmatory factor analysis (CFA) of the MSI-06 survey data; Rwg
      coefficients of homogeneity were calculated for 37 units and six organizations in
      the MSI-06 data set to examine within-group agreement. PRINCIPAL FINDINGS: The
      CFA did not yield acceptable levels of fit. EFA and reliability analysis of MSI
      06 data suggest two reliable dimensions of PSC: Organization leadership for
      safety (alpha=0.88) and Unit leadership for safety (alpha=0.81). Within-group
      agreement analysis shows stronger within-unit agreement than within-organization
      agreement on assessed PSC dimensions. CONCLUSIONS: The field of PSC measurement
      has not been able to meet strict requirements for sound measurement using
      conventional approaches of CFA. Additional work is needed to identify and soundly
      measure key dimensions of PSC. The field would also benefit from further
      attention to strength of culture/unit of analysis issues.

PMID- 18823447
TI  - Transportation brokerage services and Medicaid beneficiaries' access to care.
AB  - OBJECTIVE: To examine the effect of capitated transportation brokerage services
      on Medicaid beneficiaries' access to care and expenditures. DATA SOURCES/STUDY
      SETTING: The study period from 1996 to 1999 corresponds to the period of a
      natural experiment during which Georgia and Kentucky implemented transportation
      brokerage services. Effects were estimated for asthmatic children and diabetic
      adults. STUDY DESIGN: We used difference-in-differences models to assess the
      effects of transportation brokerage services on access to care, measured by
      Medicaid expenditures and health services use. The study design is strengthened
      by the staggered implementation dates between states and within each state.
      PRINCIPAL FINDINGS: For asthmatic children, transportation brokerage services
      increased nonemergency transportation expenditures and the likelihood of using
      any services; reductions in monthly expenditures more than offsetting the
      increased transportation costs. For diabetic adults, nonemergency transportation
      costs decreased despite increased monthly use of health services; average monthly
      medical expenditures and the likelihood of hospital admission for an ambulatory
      care-sensitive condition (ACSC) also decreased. CONCLUSIONS: The shift to
      transportation brokerage services improved access to care among Medicaid
      beneficiaries and decreased the expenditures. The increase in access combined
      with reduced hospitalizations for asthmatic children and ACSC admissions for
      diabetic adults are suggestive of improvements in health outcomes.

PMID- 18823448
TI  - Effects of state minimum staffing standards on nursing home staffing and quality
      of care.
AB  - OBJECTIVE: To investigate the impact of state minimum staffing standards on the
      level of staffing and quality of nursing home care. DATA SOURCES: Online Survey
      and Certification Reporting System (OSCAR) merged with the Area Resource File
      from 1998 through 2001. STUDY DESIGN: Between 1998 and 2001, 16 states
      implemented or expanded staffing standards in excess of federal requirements,
      creating a natural experiment in comparison with facilities in states without new
      standards. Difference-in-differences models using facility fixed effects were
      estimated to determine the effect of state standards. DATA COLLECTION/EXTRACTION
      METHODS: OSCAR data were linked to the data on market conditions and state
      policies. A total of 55,248 facility-year observations from 15,217 freestanding
      facilities were analyzed. PRINCIPAL FINDINGS: Increased standards resulted in
      small staffing increases for facilities with staffing initially below or close to
      new standards. Yet the standards were associated with reductions in restraint use
      and the number of total deficiencies at all types of facilities. CONCLUSIONS:
      Mandated staffing standards affect only low-staff facilities facing potential for
      penalties, and effects are small. Selected facility-level outcomes may show
      improvement at all facilities due to a general response to increased standards or
      to other quality initiatives implemented at the same time as staffing standards.

PMID- 18823449
TI  - Validity of selected AHRQ patient safety indicators based on VA National Surgical
      Quality Improvement Program data.
AB  - OBJECTIVES: To examine the criterion validity of the Agency for Health Care
      Research and Quality (AHRQ) Patient Safety Indicators (PSIs) using clinical data
      from the Veterans Health Administration (VA) National Surgical Quality
      Improvement Program (NSQIP). DATA SOURCES: Fifty five thousand seven hundred and
      fifty two matched hospitalizations from 2001 VA inpatient surgical discharge data
      and NSQIP chart-abstracted data. STUDY DESIGN: We examined the sensitivities,
      specificities, positive predictive values (PPVs), and positive likelihood ratios
      of five surgical PSIs that corresponded to NSQIP adverse events. We created and
      tested alternative definitions of each PSI. DATA COLLECTION: FY01 inpatient
      discharge data were merged with 2001 NSQIP data abstracted from medical records
      for major noncardiac surgeries. PRINCIPAL FINDINGS: Sensitivities were 19-56
      percent for original PSI definitions; and 37-63 percent using alternative PSI
      definitions. PPVs were 22-74 percent and did not improve with modifications.
      Positive likelihood ratios were 65-524 using original definitions, and 64-744
      using alternative definitions. "Postoperative respiratory failure" and
      "postoperative wound dehiscence" exhibited significant increases in sensitivity
      after modifications. CONCLUSIONS: PSI sensitivities and PPVs were moderate. For
      three of the five PSIs, AHRQ has incorporated our alternative, higher sensitivity
      definitions into current PSI algorithms. Further validation should be considered
      before most of the PSIs evaluated herein are used to publicly compare or reward
      hospital performance.

PMID- 18823450
TI  - Teaching neurology by videolink.

PMID- 18823451
TI  - Host ecology and life-history traits associated with blood parasite species
      richness in birds.
AB  - Identifying host traits associated with the number of different parasite species
      or strains harboured by a particular host species can have important implications
      for understanding the impact of parasitism on hosts. We investigated associations
      between host ecology and life history, and parasite richness and prevalence of
      the four major avian blood parasite genera. We used an extensive data on blood
      parasite infections and host ecology in 263 bird species from the Western
      Palearctic, combining species-specific data with a comparative approach to
      control for similarity in phenotype among host species due to the effects of
      common phylogenetic descent. Adult survival rate negatively correlated with the
      number of parasite species infecting a host species when controlling for
      similarity due to common descent and body mass. In addition, the prevalence of
      Haemoproteus, Plasmodium and Leucocytozoon was higher in species harbouring a
      richer parasite assemblage. These results suggest that the impact on host fitness
      caused by avian haematozoa may be underestimated in natural populations if the
      exacerbated virulence associated with exposure to multiple parasites is not taken
      into account.

PMID- 18823452
TI  - What, if anything, is sympatric speciation?
AB  - Sympatric speciation has always fascinated evolutionary biologists, and for good
      reason; it pits diversifying selection directly against the tendency of sexual
      reproduction to homogenize populations. However, different investigators have
      used different definitions of sympatric speciation and different criteria for
      diagnosing cases of sympatric speciation. Here, we explore some of the
      definitions that have been used in empirical and theoretical studies. Definitions
      based on biogeography do not always produce the same conclusions as definitions
      based on population genetics. The most precise definitions make sympatric
      speciation an infinitesimal end point of a continuum. Because it is virtually
      impossible to demonstrate the occurrence of such a theoretical extreme, we argue
      that testing whether a case fits a particular definition is less informative than
      evaluating the biological processes affecting divergence. We do not deny the
      importance of geographical context for understanding divergence. Rather, we
      believe this context can be better understood by modelling and measuring
      quantities, such as gene flow and selection, rather than assigning cases to
      discrete categories like sympatric and allopatric speciation.

PMID- 18823453
TI  - Genetically engineered rice containing larger amounts of nicotianamine to enhance
      the antihypertensive effect.
AB  - Nicotianamine (NA), a metal chelator ubiquitous in higher plants, serves as an
      antihypertensive substance in humans. To engineer a novel antihypertensive rice
      that contains larger amounts of NA, the barley NA synthase gene, HvNAS1, was
      introduced into rice via Agrobacterium-mediated transformation. The introduced
      HvNAS1 was driven by pGluB-1, which induces strong gene expression in the
      endosperm of rice seeds. The NA content in transgenic rice seeds was up to
      fourfold greater than that in non-transgenic rice seeds. The Cre/loxP DNA
      excision (CLX) system was used to remove the selectable marker gene for
      antibiotic resistance. Furthermore, the transgenic rice was crossed with a
      cleistogamous mutant to prevent gene transfer via pollen dispersal. These two
      modifications may minimize public concern with regard to the use of this
      transgenic rice.

PMID- 18823455
TI  - Meta-analysis of the diagnostic accuracy of transesophageal echocardiography for
      assessment of atherosclerosis in the ascending aorta in patients undergoing
      cardiac surgery.
AB  - BACKGROUND: Stroke after cardiac surgery may be caused by emboli emerging from an
      atherosclerotic ascending aorta (AA). Epiaortic ultrasound scanning (EUS), the
      current 'gold' standard for detecting AA atherosclerosis, has not gained
      widespread use because there is a lack of optimized ultrasound devices, it
      lengthens the procedure, it endangers sterility, and there is a false belief by
      many surgeons that palpation is as sensitive as EUS. Furthermore there is no
      clear evidence proving that the use of epiaortic scanning changes outcome in
      cardiac surgery. Various researchers investigated the ability of transesophageal
      echocardiography (TEE) to discriminate between the presence and absence of AA
      atherosclerosis. It is acknowledged that TEE has limited value in this, but it
      has never been supported by a meta-analysis estimating the true diagnostic
      accuracy of TEE based on all quantitative evidence. We aimed to do this using
      state-of-the-art methodology of diagnostic meta-analyses. METHODS: We searched
      multiple databases for studies comparing TEE vs. EUS for detection of
      atherosclerosis. A random-effects bivariate meta-regression model was used to
      obtain summary estimates of sensitivity and specificity, incorporating the
      correlation between sensitivity and specificity as well as covariates to explore
      heterogeneity across studies. RESULTS: We extracted six studies with a total of
      346 patients, of whom 419 aortic segments were analyzed, including 100 segments
      with atherosclerosis [median prevalence 25% (range 17-62%)]. Summary estimates of
      sensitivity and specificity were 21% (95% CI 13-32%) and 99% (96-99%),
      respectively. CONCLUSIONS: Because of the low sensitivity of TEE for the
      detection of AA atherosclerosis, a negative test result requires verification by
      additional testing using epiaortic scanning. In case of a positive test result,
      AA atherosclerosis can be considered as present, and less manipulative strategies
      might be indicated.

PMID- 18823454
TI  - Platelet-derived growth factor-B gene delivery sustains gingival fibroblast
      signal transduction.
AB  - BACKGROUND AND OBJECTIVE: Platelet-derived growth factor-BB is a potent mediator
      of tooth-supporting periodontal tissue repair and regeneration. A limitation of
      the effects of topical platelet-derived growth factor-BB application is its short
      half-life in vivo. Gene therapy has shown strong promise for the long-term
      delivery of platelet-derived growth factor in both skin ulcer healing and
      periodontal tissue engineering. However, little is known regarding the extended
      effects of platelet-derived growth factor-B on cell signaling via gene delivery,
      especially at the level of phosphorylation of intracellular kinases. This study
      sought to evaluate the effect of gene transfer by Ad-PDGF-B on human gingival
      fibroblasts (HGFs) and the subsequent regulation of genes and cell-surface
      proteins associated with cellular signaling. MATERIAL AND METHODS: HGFs from
      human subjects were treated by adenoviral PDGF-B, PDGF-1308 (a dominant negative
      mutant of PDGF) and recombinant human platelet-derived growth factor-BB, and then
      incubated in serum-free conditions for various time points and harvested at 1, 6,
      12, 24, 48, 72 and 96 h. Exogenous PDGF-B was measured by RT-PCR and Western
      blot. Cell proliferation was evaluated by [methyl-3H]thymidine incorporation
      assay. We used proteomic arrays to explore phosphorylation patterns of 23
      different intracellular kinases after PDGF-B gene transfer. The expression of
      alpha and beta PDGFR and Akt were measured by Western blot analysis. RESULTS:
      Sustained in vitro expression of PDGF-B in HGFs by Ad-PDGF-B transduction was
      seen at both the mRNA and protein levels. Compared to rhPDGF-BB and Ad-PDGF-1308,
      Ad-PDGF-B maintained cell growth in serum-free conditions, with robust increases
      in DNA synthesis. Gene delivery of PDGF-B also prolonged downregulation of the
      growth arrest specific gene (gas) PDGF alpha R. Of the 23 intracellular kinases
      that we tested in proteomic arrays, Akt revealed the most notable long-term cell
      signaling effect as a result of the over-expression of Ad-PDGF-B, compared with
      pulse recombinant human platelet-derived growth factor BB. Prolonged Akt
      phosphorylation was induced by treatment with Ad-PDGF-B, for at least up to 96 h.
      CONCLUSION: These findings further demonstrate that gene delivery of PDGF-B
      displays sustained signal transduction effects in human gingival fibroblasts that
      are higher than those conveyed by treatment with recombinant human platelet
      derived growth factor-BB protein. These data on platelet-derived growth factor
      gene delivery contribute to an improved understanding of these pathways that are
      likely to play a role in the control of clinical outcomes of periodontal
      regenerative therapy.

PMID- 18823456
TI  - Post-conditioning reduces infarct size in an open-chest porcine acute ischemia
      reperfusion model.
AB  - BACKGROUND: Timely reperfusion is a prerequisite for myocardial salvage; however,
      re-oxygenation of the ischemic myocardium initiates reperfusion injury. Post
      conditioning diminishes the detrimental aftermath of an acute myocardial
      infarction through alleviation of reperfusion injury. Ischemic post-conditioning
      consists of a series of brief interruptions in the coronary blood supply that has
      to be applied within the first minutes after re-establishing the coronary flow.
      METHODS: Sixteen female mixed Danish Landrace and Yorkshire pigs weighing 20 kg
      were included. The heart was exposed through a midline sternotomy. A snare was
      positioned around the left anterior descending coronary artery downstream of the
      second diagonal branch. After randomization to either no treatment (control
      group) or treatment by ischemic post-conditioning (post-conditioning group), the
      pigs underwent 45 min of ischemia and 180 min of reperfusion. The post
      conditioning group had a post-conditioning algorithm applied consisting of 15 s
      of reperfusion alternating with 15 s of re-occlusion repeated 10 times. RESULTS:
      The groups were comparable with regard to body weight, hemodynamics and the size
      of the area at risk. The post-conditioning group had an absolute reduction in
      infarct size of 18.1% [confidence interval (CI): 6.2: 30.0%] compared with the
      control group (P=0.0056). In the post-conditioning group, infarction developed in
      39.6+/-12.0% (1 SD) of the area at risk compared with 57.8+/-10.2% (1 SD) in the
      control group. CONCLUSION: When ischemic post-conditioning was applied at
      reperfusion, we found an absolute reduction in infarct size of 18.1% presumably
      attributable to a diminished reperfusion injury. The model we have developed is
      suitable for further studies of this promising intervention.

PMID- 18823457
TI  - Establishment of a porcine right ventricular infarction model for
      cardioprotective actions of xenon and isoflurane.
AB  - BACKGROUND: Right ventricular (RV) function is an important determinant of post
      operative outcome. Consequences of RV infarction might be limited by pre
      conditioning with volatile anesthetic drugs. Therefore, we used a porcine model
      of RV ischemia and reperfusion (IR) injury to study the influence of isoflurane
      and xenon on the extent and degree of myocardial injury. METHODS: IR injury was
      induced by a 90-min ligation of the distal right coronary artery and 120-min
      reperfusion in thiopental anesthetized pigs. A control group (n=12) was compared
      with two groups, which received either 0.55 minimum alveolar concentration (MAC)
      isoflurane (n=10) or xenon (n=12) starting 60 min before ischemia. Myocardial
      injury was described by three criteria: the infarct size related to area at risk
      (IS/AAR), the infiltration of neutrophils as determined by myeloperoxidase (MPO)
      activity, and the plasma levels of tumor necrosis factor alpha (TNFalpha),
      interleukin 6 (IL-6), myoglobin and troponin-T (TnT). RESULTS: IS/AAR was reduced
      from 58.3+/-6.2% in the control group to 41.8+/-7.8% after isoflurane and 42.7+/
      8.5% after xenon pre-treatment, which equals an absolute reduction of 16.5% [95%
      confidence interval (CI): 10.9-22.1] and 15.5% (95% CI: 10.1-20.9). The maximum
      increase of TnT could be observed within the xenon group. Both treatment groups
      were characterized by lower MPO activity, in the infarct and periinfarct region
      and lower plasma concentrations of TNFalpha and IL-6. CONCLUSIONS: It could be
      demonstrated for the first time in a model of RV infarction that the continuous
      application of isoflurane or xenon before, during and after ischemia reduced the
      extent (size) and severity (inflammation) of myocardial injury.

PMID- 18823458
TI  - The inflammatory response to colloids and crystalloids used for pump priming
      during cardiopulmonary bypass.
AB  - BACKGROUND: Systemic inflammatory response frequently occurs after coronary
      artery bypass surgery and is strongly correlated with the risk of postoperative
      morbidity and mortality. This study tests the hypothesis that the priming of the
      extracorporeal circuit with colloid solutions results in less inflammation in
      patients undergoing cardiac surgery than priming with crystalloid solutions.
      METHODS: A prospective, randomized study was designed. Forty-four patients
      undergoing elective coronary artery bypass grafting were randomly allocated to
      one of two groups: 22 patients primed with Ringer's lactate (RL) solution and 22
      patients primed with gelatin-containing solution during the surgery. Plasma
      levels of interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-alpha, C-reactive
      protein (CRP) and, complement 4 were measured during the surgical intervention
      and over the following 48 postoperative hours. Cytokine levels were measured by
      enzyme-linked assays from plasma samples obtained at specific time points pre-
      and post-operatively. RESULTS: In both groups the serum levels of the pro
      inflammatory cytokines (IL-6, IL-8, TNF-alpha), CRP, complement 4, and leukocytes
      increased significantly over the baseline, although no significant differences
      were observed between the two groups. The operation time, blood loss, need for
      inotropic support, extubation time, and length of intensive care unit stay did
      not differ significantly between the two groups. CONCLUSION: Priming with gelatin
      vs. RL produces no significant differences in the inflammatory response in
      patients undergoing coronary artery bypass grafting with cardiopulmonary bypass.

PMID- 18823459
TI  - Correlation between central venous oxygen saturation and oxygen delivery changes
      following fluid therapy.
AB  - BACKGROUND: The rationale for using central venous oxygen saturation (ScvO(2)) in
      various clinical scenarios is that it reflects the balance between oxygen
      delivery (DO(2)) and demands. In this study, we evaluated the correlation between
      ScvO(2) and DO(2) changes (Delta Do(2), DeltaScvO(2)) in patients receiving fluid
      therapy following coronary surgery. We also correlated the changes of mean
      arterial pressure (Delta MAP) and central venous pressure (Delta CVP), with Delta
      DO(2). METHODS: Sixty consecutive sedated and mechanically ventilated adult
      patients, with cardiac index <or=2.3 L/min/m(2) and a pulmonary artery occlusion
      pressure <or=12 mmHg following coronary surgery, were included. Concomitant
      hemodynamic parameters, arterial and venous blood gases were measured before (T0)
      and after (T1) administration of a 500 ml bolus of an isotonic crystalloid
      solution over 30 min. The correlations between Delta DO(2) and DeltaScvO(2),
      Delta MAP or Delta CVP were evaluated by linear regression analysis and Pearson
      test. RESULTS: Cardiac index (1.9+/-0.2 vs 2.3+/-0.5 ml/min/m(2)), MAP (83+/-11
      vs 94+/-13 mm Hg) and CVP (5.7+/-3 vs 7.1+/-3 mmHg) were significantly higher at
      T1 compared with T0. The correlation of Delta DO(2) with DeltaScvO(2) was
      positive, significant (r=0.41; P=0.004) and superior to its correlation with
      Delta MAP (r=0.30; P=0.01) or Delta CVP (r=0.03; P=0.78). CONCLUSION: A
      significant correlation between ScvO(2) and DO(2) changes was found in patients
      receiving fluid therapy following coronary surgery. ScvO(2) could be used as an
      indicator to track DO(2) and to guide volume loading.

PMID- 18823460
TI  - Influence of pre-operative fluid infusion on volume status during oesophageal
      resection--a prospective trial.
AB  - BACKGROUND: Perioperative fluid therapy is controversially debated in surgery. In
      malnourished and hypovolaemic patients, a restrictive fluid regimen may lead to
      hypoperfusion and increased incidence of complications. The present prospective
      cohort study was performed to assess whether pre-operative i.v. fluid
      administration improves intraoperative cardiac preload in patients undergoing
      oesophageal resection. METHODS: Intraoperatively, the intrathoracic blood volume
      index (ITBVI) was monitored in 44 consecutive patients undergoing elective
      oesophagectomies with the transthoracic thermodilution technique. Twenty-two of
      these patients received a pre-operative i.v. fluid loading with a balanced
      crystalloid solution (1 ml/kg/h over 48 h). RESULTS: After induction of
      anaesthesia ITBVI was low but not different between the groups [767 (512-1314)
      vs. 775 (531-1200) ml/m(2), P=0.81]. In the intervention group, the extravascular
      lung water increased above normal levels during the operation. The groups did not
      differ in cardiac output, blood pressure, heart rate and central venous pressure.
      Post-operative morbidity was not different between the cohorts. CONCLUSION: Pre
      operative i.v. fluid loading with crystalloid solutions could not be shown to
      improve the intraoperative volume status and cardiac function in this study.
      Randomised trials with other volume replacement techniques are recommended.

PMID- 18823461
TI  - Bleeding time prolonged by daily low-dose aspirin is shortened by one medium dose
      aspirin.
AB  - BACKGROUND: In planning surgery, a low-dose aspirin regimen for prevention of
      thrombotic events is often discontinued in order to avoid the risk of excessive
      bleeding during surgery. However, this procedure increases the risk from adverse
      thrombotic events. We propose a different method, which may normalize the
      prolonged bleeding time caused by low-dose aspirin. We verified the effectiveness
      of this method in healthy volunteers. METHODS: Volunteers with bleeding time
      prolonged by taking 81 mg of aspirin a day for a period of 1 week were randomly
      divided into two groups. The test group of 18 volunteers received a dose of 660
      mg of aspirin, while the control group of 16 received placebo. Bleeding time and
      maximum platelet activity were then evaluated. RESULTS: Before 660 mg of aspirin
      or placebo, bleeding time was prolonged: in the aspirin group from 3.1 +/- 0.7 to
      6.1 +/- 1.4 min (n=18), and in the placebo group from 2.9 +/- 0.9 to 6.1 +/- 1.5
      min (n=16). This prolongation was significant in both groups at the P<0.01 level.
      In the test group, bleeding time was shortened to 4.5 +/- 1.3 min (P<0.01), which
      is in the normal range, while it remained prolonged in the control group (6.0 +/-
      1.2 min). Platelet activity, on the other hand, was suppressed in both groups.
      CONCLUSION: We conclude that 660 mg of aspirin effectively shortens the bleeding
      time prolonged by daily low-dose (81 mg) aspirin.

PMID- 18823462
TI  - Early time course of altered leukocyte response to lipopolysaccharide and
      peptidoglycan in porcine gunshot injury.
AB  - BACKGROUND: Penetrating injuries are frequently combined with polybacterial
      soiling. Clearance of the microorganisms depends on the ability to activate
      immune responses, but post-traumatic hyporeactivity of immune cells is almost
      universal. The aim of this study was to map the early time course of this altered
      leukocyte reactivity, and to compare the reactions to subsequent Gram-positive or
      Gram-negative challenges. METHODS: Twelve juvenile pigs sustained two
      standardized rounds, one through the right femur and one through the left upper
      abdomen. First aid treatment and acute surgery were started immediately. Blood
      samples were drawn before trauma and after 10, 30, 60, and 90 min, and thereafter
      stimulated in ex vivo whole blood for 3 h with lipopolysaccharide (LPS, 10
      ng/ml), peptidoglycan (PepG, 1 microg/ml), or an equivalent amount of normal
      saline. The leukocyte response was evaluated by measurement of tumor necrosis
      factor (TNF)-alpha, interleukin (IL)-1 beta, IL-6, IL-8, and IL-10 in the
      supernatant. RESULTS: In the post-traumatic in vivo serum, the concentration of
      TNF-alpha increased steadily (significant after 60 min). A reduced ex vivo
      reaction to LPS was evident after 10 min, and was statistically significant after
      30 min. The lowest levels were reached after 90 min. The ex vivo synthesis of TNF
      alpha after stimulation with PepG remained unaltered. A similar development was
      seen for IL-6. IL-1 beta levels did not change, while IL-8 increased
      significantly only after 60 and 90 min. CONCLUSIONS: Trauma almost
      instantaneously reprogrammed circulating leukocytes. As measured with TNF-alpha,
      a profound hyporeactivity to LPS, but not to PepG, was induced. In addition, no
      global down-regulation of leukocyte function was found after stimulation with
      LPS.

PMID- 18823463
TI  - Risk factors and outcome in ICU-acquired infections.
AB  - BACKGROUND: Nosocomial infections are common in intensive care units (ICU). The
      objectives of this study were to determine risk factors of ICU-acquired
      infections, and potential mortality attributable to such infections. METHODS: An
      observational study was performed in a 10-bed multidisciplinary ICU. For a period
      of 27 months, all patients admitted for >or=48 h were included. Infections were
      diagnosed according to Centers for Disease Control and Prevention definitions.
      Airway colonization was explored by molecular typing. Risk factors for infection
      were determined by multivariable logistic regression. Survival was analyzed with
      time-varying proportional hazards regression. RESULTS: Of 278 patients, 81 (29%)
      were infected: urinary tract infections in 39 patients (14%), primary bloodstream
      infections in 25 (9%), surgical site infections in 22 (8%) and pneumonia in 21
      (8%). Of the total of 147 episodes, Gram-negative bacilli were isolated in 90,
      Gram-positive cocci in 49 and Candida sp. in 25. Risk factors for pneumonia were
      mechanical ventilation [odds ratio (OR=7.9, CI 1.8-35), lack of enteral nutriment
      (OR=8.0, CI 1.4-45) and length of time at risk (OR=1.8, CI 1.2-2.8), while
      gastric acid inhibitors did not affect the risk (OR=0.99, CI 0.32-3.0).
      Transmission of bacteria from the stomach to the airway was not confirmed. The
      risk of death was increased as patients were infected with pneumonia [hazard
      ratio (HR)=3.6; CI: 1.6-8.1], or primary bloodstream infection (HR=2.5; CI: 1.2
      5.4), independent of age and disease severity. CONCLUSIONS: Mortality was
      increased by ICU-acquired pneumonia and primary bloodstream infections. Our
      findings did not support the gastro-pulmonary hypothesis of ICU-acquired
      pneumonia. The proposition that blood transfusions increase the risk of ICU
      acquired nosocomial infections was not supported.

PMID- 18823464
TI  - Effects of recombinant human activated protein C on the coagulation system: a
      study with rotational thromboelastometry.
AB  - BACKGROUND: Recombinant human activated protein C (rhAPC) is an anticoagulant
      that can be used for treatment of patients with severe sepsis. The use of rhAPC
      is accompanied by an increased risk of severe bleeding. Rotational
      thromboelastometry is a method for measuring the status of the coagulation. The
      aim of the study was to investigate whether rotational thromboelastometry could
      be used for monitoring the effects of rhAPC on the coagulation. METHODS: Whole
      blood was mixed in vitro with concentrations of rhAPC ranging from 0 to 75 ng/ml
      and analysed with rotational thromboelastometry. RESULTS: The parameter
      Coagulation Time was significantly prolonged by increasing the concentrations of
      rhAPC (P=0.002). Other parameters were not significantly affected. CONCLUSION:
      rhAPC dose dependently affects the early humoral parts of the coagulation, while
      platelet function and fibrinogen to fibrin conversion seem virtually unaffected.

PMID- 18823465
TI  - Post-operative pressure lability and cardiac baroreflex in normotensive patients
      as a function of age.
AB  - BACKGROUND: Pressure lability may be linked to the loss of the cardiac
      baroreflex. The reduction of the sensitivity of the cardiac baroreflex has not
      been delineated in the post-operative period according to age in normotensive
      patients. This study addresses pressure lability and slope of the cardiac
      baroreflex as a function of age. METHODS: Patients were allocated to the
      following three groups: young (20-39 years, n=7), middle aged (40-59 years, n=7)
      and elderly (60-79 years, n=6), and studied before minor intra-abdominal surgery
      under CO(2) peritoneal insufflation and nitrous oxide-isoflurane-sufentanil
      anesthesia, up to 24 h after extubation. An electrocardiogram and non-invasive
      beat-by-beat pressure monitoring (Finapres) allowed offline calculation of the
      sensitivity of the cardiac baroreflex ('sequence' technique) and standard
      deviation (SD) of heart rate (HR; HR variability) and systolic blood pressure
      (SBP; pressure lability). RESULTS: Before anesthesia, (a) an inverse relationship
      was observed between the slope of the cardiac baroreflex and age and (b) a trend
      (P<0.09) existed between the slope of the cardiac baroreflex and pressure
      lability, irrespective of age. During the early post-operative period, young
      patients returned to their baseline slope of the cardiac baroreflex; no inverse
      relationship between increased SD of SBP and decreased SD of RR interval was
      observed. Middle-aged and elderly patients displayed a depressed slope of the
      cardiac baroreflex both before and after anesthesia. CONCLUSION: At variance with
      the pre-operative period, no simple inverse relationship was observed between
      increased pressure lability and depressed HR variability in young patients during
      the early post-operative period.

PMID- 18823466
TI  - Sepsis-related acute kidney injury: a protective effect of drotrecogin alpha
      (activated) treatment?
AB  - BACKGROUND: Drotrecogin alpha activated (DrotAA) is licensed for treatment of
      patients with severe sepsis and organ failure. Among the latter, acute kidney
      injury (AKI), defined as the persistence of oligo-anuria following adequate
      resuscitation, is one of the most apprehended. We conducted a prospective,
      observational, and controlled study to test the hypothesis that DrotAA
      beneficially affected the evolution and outcome of AKI, complicating acute sepsis
      induced cardiopulmonary failure. METHODS: Forty-six patients were studied. Thirty
      subjects received standard treatment for sepsis without DrotAA. In the remaining
      16 patients, DrotAA was added as a continuous infusion of 24 microg/kg/h for 96
      h. RESULTS: Mean age, causes of sepsis, and severity/organ failure scores were
      comparable between patients treated with or without DrotAA. Mortality at 28 days
      was high and comparable between both treatment groups (56% vs. 69%, DrotAA vs. no
      DrotAA; P=0.5). When oligo-anuria was present at the start of the study, it
      persisted during treatment in all patients, with no significant difference
      between groups. Both treatment groups presented with baseline mean daily
      fractional excretion of sodium values >2% that remained high during the
      observation period, regardless of whether DrotAA was given or not. Kidney
      histology showed a preserved renal architecture with tubular necrosis in all
      specimens. Similar glomerular, tubulo-interstitial, and vascular alterations were
      present in both treatment groups. CONCLUSION: In this small cohort of patients
      with severe sepsis who received adjuvant DrotAA treatment, no effect on urine
      output, tubular function, or mortality could be demonstrated.

PMID- 18823467
TI  - Prognostic merit of N-terminal-proBNP and N-terminal-proANP in mechanically
      ventilated critically ill patients.
AB  - BACKGROUND: Amino-terminal fragments of type-A and type-B natriuretic peptide
      prohormones (NT-proBNP, NT-proANP) are powerful prognostic markers in patients
      with cardiac disease, and NT-proBNP has been demonstrated to predict outcome in
      severe sepsis and septic shock. We assessed the prognostic value of NT-proBNP and
      NT-proANP in a consecutive series of mechanically ventilated intensive care
      patients and compared their prognostic merit. METHODS: Seventy unselected
      patients admitted to the intensive care unit (ICU) were included in the study 48
      h after start of controlled mechanical ventilation. Venous blood was obtained on
      inclusion and assayed for NT-proBNP and NT-pro ANP. Univariate and multivariate
      logistic regression analysis was used to assess the association of NT-proBNP and
      NT-proANP levels with 30-day mortality. Established risk factors and possible
      confounders were used as covariates. Discrimination of different prognostic
      models was assessed calculating the area under the receiver-operating
      characteristics curve (ROC-AUC). RESULTS: NT-proBNP and NT-proANP levels were
      higher in non-survivors (n=25) than in 30-day survivors (n=45). Log NT-proBNP
      [odds ratio (OR) 2.34, 95% CI 1.17-4.66], and log NT-proANP (OR 2.44, 95% CI 1.12
      5.30) were independently predictive of increased mortality. A prior diagnosis of
      chronic obstructive lung disease was predictive of decreased mortality (OR 0.29,
      95% CI 0.08-1.00). The relative prognostic values, evaluated by the ROC-AUCs of
      NT-proBNP (AUC 0.74, 95% CI 0.61-0.86) and NT-proANP (AUC 0.73, 95% CI 0.61
      0.86), were nearly identical. CONCLUSIONS: High NT-proANP and NT-proBNP levels
      associated with decreased short-term survival in unselected, mechanically
      ventilated ICU patients. NT-proANP performed equally well as a prognostic
      indicator as NT-proBNP, and may represent a clinically useful alternative to NT
      proBNP.

PMID- 18823468
TI  - Effect of remifentanil on oculocardiac reflex in paediatric strabismus surgery.
AB  - BACKGROUND: Rapidly acting narcotics enhance the degree of bradycardia due to the
      oculocardiac reflex (OCR) elicited by extraocular muscle (EOM) tension during
      strabismus surgery. We evaluated and compared the effects of remifentanil and
      sevoflurane on OCR during paediatric strabismus surgery. METHODS: One hundred and
      twenty children, 1-9 years old, undergoing elective strabismus surgery, were
      randomly assigned to receive sevoflurane or remifentanil. No anticholinergic
      prophylaxis was administered. Anaesthesia was induced using ketamine 1.0 mg/kg or
      midazolam 0.15 mg/kg with 66% N(2)O in O(2). Laryngeal mask airways were placed
      with rocuronium 0.5 mg/kg. Anaesthesia was maintained with sevoflurane 2.0-3.0
      vol% with 66% N(2)O in O(2) or remifentanil 0.75 mug/kg over 1 min and followed
      by the continuous infusion of remifentanil 0.5 mug/kg/min with 66% N(2)O in O(2).
      Heart rate (HR) and blood pressure (BP) were measured and compared. OCR was
      defined as a reduction in HR of >20% induced by traction of an EOM. RESULTS:
      During anaesthesia, HR and BP were maintained at a lower level in the
      remifentanil group than in the sevoflurane group (each, P<0.05). The mean percent
      change in HR (-23.3+/-17.0% vs. -11.2+/-13.0%; P<0.05) and the incidence of OCR
      (58.3% vs. 28.3%; P<0.05) following traction of an EOM were higher in the
      remifentanil group than in the sevoflurane group. CONCLUSIONS: Remifentanil
      enhanced the degree of bradycardia due to OCR as compared with sevoflurane during
      paediatric strabismus surgery.

PMID- 18823469
TI  - Comparison of etoricoxib vs. ketorolac in postoperative pain relief.
AB  - BACKGROUND: COX-2 inhibitors have been claimed to have equal analgesic efficacy
      as non-selective nonsteroidal anti-inflammatory drugs, but this has been disputed
      in animal experiments. METHODS: One hundred thirty-three women scheduled for
      ambulatory, laparoscopic gynaecological surgery were included in this randomised,
      double-blind study. Group E received 120 mg etoricoxib orally as premedication.
      Group K received 30 mg ketorolac i.v. after induction of anaesthesia. General
      anaesthesia was induced and maintained with propofol and remifentanil. Fentanyl
      0.5 microg/kg i.v. and local wound anaesthesia was administered at the end of
      surgery. Postoperatively, the patients received fentanyl 0.5 microg/kg i.v. if
      visual analogue scale (VAS) >or=30 mm. Before discharge, Group K received 30 mg
      ketorolac i.v. Twenty-four hours postoperatively, Group E received 120 mg
      etoricoxib. RESULTS: The first 4 h postoperatively, Group K required 83+/-65
      microg and Group E required 123+/-91 microg fentanyl [mean (SD), P=0.004]. After
      30 min VAS in Group K was 31.3+/-19.7 mm and 43.8+/-16.9 mm in Group E [mean
      (SD), P<0.001]. Discharge readiness was significantly shorter in Group K (222+/
      40 min) compared with Group E (244+/-47 min) [mean (SD), P=0.004]. There were no
      differences in pain scores or rescue pain medication at 24 or 48 h
      postoperatively. Less nausea was observed in the 4-24-h period in Group E.
      CONCLUSIONS: Thirty milligram ketorolac i.v. after induction of anaesthesia
      resulted in significantly less immediate pain and opioid consumption during the
      first 4 h postoperatively compared with 120 mg etoricoxib preoperatively.

PMID- 18823470
TI  - Comparison of three doses of epidural fentanyl followed by bupivacaine and
      fentanyl for labor analgesia.
AB  - BACKGROUND: Epidural fentanyl 100 microg after lidocaine-epinephrine test dose
      has been shown to provide adequate analgesia in early labor. This investigation
      determines the effect of three different bolus doses of epidural fentanyl on
      duration and quality of analgesia during early first stage of labor. METHODS: In
      this prospective, double-blind study, 103 laboring nulliparous at cervical
      dilation <5 cm were enrolled. After an epidural test dose of lidocaine (60 mg)
      with epinephrine (15 microg), parturients received, randomly, bolus of epidural
      fentanyl 50, 75, or 100 microg, followed by a continuous infusion of epidural
      bupivacaine 0.0625% and fentanyl 3 microg/ml at a rate of 10 ml/h. Pain scores
      and maternal sedation, pruritus, nausea, and vomiting were recorded 10, 20, and
      30 min after fentanyl, and every 30 min thereafter until first request for
      additional analgesia. RESULTS: Adequate analgesia was achieved in 87% (28/32),
      94% (35/38), and 94% (31/33) in the fentanyl 50, 75, and 100 microg groups within
      20 min. Mean duration of analgesia before re-dosing was significantly longer in
      fentanyl 100 and 75 microg groups (185.6+/-82.9 and 188.5+/-82.2 min,
      respectively) as compared with fentanyl 50 microg group (133.6+/-46.2 min,
      P<0.016). There was no difference in the incidence of maternal side effects or
      neonatal Apgar scores among the three groups. CONCLUSION: After a test dose of
      lidocaine-epinephrine, the three epidural fentanyl doses produced similar
      effective labor analgesia. However, epidural fentanyl 75 microg followed by
      epidural infusion of dilute bupivacaine and fentanyl produced longer duration of
      analgesia than fentanyl 50 microg followed by the same infusion, with no further
      prolongation when the dose of fentanyl was increased up to 100 microg.

PMID- 18823471
TI  - Significance of retrograde diastolic uterine artery blood flow during regional
      anesthesia in instrumented pregnant sheep.
AB  - BACKGROUND: We studied the interactions between uterine and placental
      hemodynamics during maternal hypotension in chronically instrumented fetal sheep.
      In addition, we investigated maternal hemodynamic characteristics, fetoplacental
      hemodynamics and fetal acid-base status when a retrograde diastolic uterine
      artery blood flow pattern is present during maternal hypotension. METHODS:
      Invasive maternal and fetal hemodynamic parameters, uterine (Q(UtA)) and
      placental (Q(UA)) volume blood flows and acid-base values were examined in 24
      chronically instrumented sheep at baseline and during epidural-induced maternal
      hypotension at 117-132 (term 145) days of gestation. Uterine artery blood flow
      velocity waveforms were obtained by Doppler ultrasonography. RESULTS: Maternal
      hypotension decreased Q(UtA) without affecting Q(UA). During hypotension, eight
      out of 24 sheep demonstrated a retrograde diastolic blood flow velocity waveform
      pattern in the uterine artery. Maternal systolic, diastolic and mean arterial
      blood pressures were significantly lower in the retrograde group than in the
      antegrade group. No statistically significant differences in Q(UtA), Q(UA) and
      fetal blood gas values were detected between the two groups during hypotension.
      CONCLUSIONS: An acute decrease in uterine artery volume blood flow during
      maternal hypotension is not compensated by increased placental volume blood flow.
      A retrograde diastolic blood flow pattern in the uterine artery is related to
      lower maternal arterial pressures, especially during diastole. A uterine artery
      retrograde diastolic blood flow pattern does not have any additional detrimental
      short-term effects on fetal acid-base status.

PMID- 18823472
TI  - Visualization of the course of the sciatic nerve in adult volunteers by
      ultrasonography.
AB  - BACKGROUND: The sciatic nerve block by the posterior approaches represents one of
      the more difficult ultrasound-guided nerve blocks. Our clinical experiences with
      these blocks indicated a point slightly distal to the subgluteal fold as an
      advantageous position to allow good ultrasonic visibility. In this study, we
      systematically scanned the sciatic nerve from the subgluteal fold to the
      popliteal crease, to determine an optimal point for ultrasonographic
      visualization. METHODS: After institutional approval and written informed
      consent, we recruited 15 volunteers to visualize the sciatic nerve from the
      subgluteal fold to the popliteal crease using a linear ultrasound probe in the
      range of 7-13 MHz. The ultrasonographic visibility of the sciatic nerve, nerve
      diameter (width and thickness), and skin-to-nerve distance at 20 equidistant
      points between the subgluteal fold and the popliteal crease were recorded.
      RESULTS: The sciatic nerve could be successfully visualized in cross-section as a
      hyperechoic structure on ultrasound in all volunteers. In the course from
      subgluteal to the popliteal area, the shape of the sciatic nerve changed from
      flat to round, while the skin-nerve distance varied with the smallest skin-nerve
      distances at the popliteal crease and at 5.4 cm (on average) distal to the
      subgluteal fold. The best ultrasonographic visibility scores were found between
      7.2 and 10.8 cm (on average) distal to the gluteal fold. CONCLUSION: Between 5.4
      and 10.8 cm from the subgluteal fold seems to be the best area to scan the
      sciatic nerve in terms of superficial nerve position and good ultrasonic
      visibility.

PMID- 18823473
TI  - Pulse oximetry in scleroderma patients: concerns.

PMID- 18823474
TI  - In reply to the letter to the editor 'What to do if the endotracheal tube will
      not pass through the nasal passage during fiberoptic nasotracheal intubation'.

PMID- 18823475
TI  - Time-motion echocardiographic examination in the identification of an unusual
      lung artifact in the ICU.

PMID- 18823476
TI  - Mask for stoma ventilation: rescue using a Rendell-Baker-Soucek mask after a
      dislodged tracheostomy tube.

PMID- 18823477
TI  - Do we really need a low central venous pressure in elective liver resection.

PMID- 18823478
TI  - Reply to 'Chronic pain after hysterectomy'.

PMID- 18823479
TI  - The tube tie revisited.

PMID- 18823480
TI  - Awake laryngeal mask insertion followed by induction of anesthesia in infants
      with the Pierre Robin sequence.

PMID- 18823482
TI  - Professionalizing psychiatry: from 'amateur' psychiatry to 'a mature' profession.

PMID- 18823485
TI  - Maternal mortality in sub-Saharan Africa: the contribution of ineffective blood
      transfusion services.
AB  - In sub-Saharan Africa, where blood supply is critically inadequate, severe
      haemorrhage is a leading cause of maternal deaths. The aim of this review was to
      estimate the impact of lack of blood on maternal deaths and identify reasons and
      potential solutions. Databases and websites from 1970 to 2007 were searched for
      information concerning maternal deaths and near misses due to haemorrhage in sub
      Saharan Africa. Original studies that provided qualitative or quantitative
      information about blood transfusion services in relation to obstetric deaths or
      near misses were included. Data about maternal haemorrhage deaths associated with
      lack of blood for transfusion and reasons for blood shortages were extracted from
      the full text of articles by two independent reviewers using predesigned, piloted
      forms. Twenty of 37 selected studies described a direct association between
      maternal deaths and lack of blood transfusions. Five of 37 provided quantitative
      information which showed that overall 26% (16-72%) of maternal haemorrhage deaths
      were due to lack of blood. Reasons included nonaffordability of blood, lack of
      blood donors, unwillingness of relatives to donate and inadequate supplies and
      transport. Lack of blood for emergency transfusions is a major, but poorly
      quantified and under-researched cause of maternal deaths in sub-Saharan Africa.
      Potential solutions include more blood donations, better financing mechanisms and
      more efficient management systems. Complementary approaches to prevent severe
      anaemia and treat hypovolaemia are important to reduce use of transfusions.

PMID- 18823486
TI  - Comparison of sublingual versus vaginal misoprostol for the induction of labour:
      a systematic review.
AB  - BACKGROUND: The induction of full-term labour in women with a live fetus remains
      a major challenge in modern obstetrics. OBJECTIVES: To determine, using the best
      level of evidence available, the efficacy and safety of sublingual administration
      of misoprostol compared with vaginal misoprostol in the third trimester of
      pregnancy for the induction of labour, according to initial doses, in women with
      a live, full-term fetus and an unripe cervix. SEARCH STRATEGY: Pubmed/Medline,
      Lilacs and Scielo databases were consulted, as well as clinical trials registered
      in the Cochrane Register from January 1996 to February 2008, using the keywords
      'misoprostol', 'labour, obstetric', 'delivery, obstetric', 'induced labour' and
      'parturition' with the search limits of 'clinical trials' and 'randomised
      clinical trials'. SELECTION CRITERIA: This review contains randomised clinical
      trials in which the sublingual and vaginal routes of administration of
      misoprostol were compared. Participants were pregnant women with an indication
      for induction of labour and a live fetus more than 37 weeks of gestational age.
      DATA COLLECTION AND ANALYSIS: The primary analysis compared sublingual and
      vaginal routes of administration of misoprostol. Secondary analyses compared
      different routes and initial doses of misoprostol. Statistical analysis included
      odds ratios and their respective 95% CI. To evaluate the heterogeneity of the
      studies, the I-squared test was used, studies being considered heterogeneous when
      I 2 was greater than 50%. MAIN RESULTS: Five good quality clinical trials
      involving a total of 740 women were eligible, and all were included. No
      statistically significant difference was found between the sublingual and the
      vaginal misoprostol groups with respect to the rate of vaginal delivery not
      achieved within 24 hours (OR 1.27, 95% CI 0.87-1.84), uterine hyperstimulation
      syndrome (OR 1.20, 95% CI 0.61-2.33) or caesarean section (OR 1.33, 95% CI 0.96
      1.85). An increased risk of uterine tachysystole was found in the sublingual
      misoprostol group (OR 1.70, 95% CI 1.02-2.83). When the studies were grouped
      according to the initial dose of misoprostol, no significant difference was found
      between sublingual or vaginal groups. AUTHOR'S CONCLUSIONS: The sublingual route
      of administration is as effective as the vaginal route in inducing labour in full
      term pregnancies with live fetuses. However, the safety, adverse effects, optimal
      dose and perinatal outcome related to this route of administration remain to be
      established, and it cannot be recommended for routine use in obstetric practice.

PMID- 18823487
TI  - The role of Lactobacillus casei rhamnosus Lcr35 in restoring the normal vaginal
      flora after antibiotic treatment of bacterial vaginosis.
AB  - OBJECTIVE: To evaluate the efficacy of additional topical Lactobacillus casei
      rhamnosus (Lcr35) subsequent to antibiotic treatment of bacterial vaginosis (BV)
      to restore the normal vaginal flora. STUDY DESIGN: Single-centre, randomised,
      observerblinded study. SETTING: Population-based study in Vienna over 1 year.
      SAMPLE: 190 women were enrolled in the study. METHODS: Women with Nugent scores
      between 7 and 10 on initial vaginal swab were randomised to the one of two
      groups. All women were treated with standard antibiotic therapy for 7 days. Only
      women in the intervention group received vaginal capsules containing 10(9) colony
      forming units of live Lcr35 for 7 days after antibiotic treatment. Final vaginal
      swabs for Nugent scoring were taken 4 weeks after the last administration of the
      study medication. MAIN OUTCOME MEASURES: The primary efficacy variable was a
      change in the Nugent score between the baseline and the end of the study of at
      least 5 grades in each individual woman. RESULTS: Sixty-nine of the 83 women
      (83%) in the intervention group and 31 of the 88 women (35%) in the control group
      showed a reduction of the Nugent score by at least 5 grades. The difference in
      the number of women with improvement was highly significant (P < 0.001). The
      median difference in Nugent scores between initial and final swabs was 6.61 in
      the intervention group and 4.13 in the control group (P < 0.001). CONCLUSION: Our
      data show that the restoration of the vaginal flora after antibiotic treatment of
      BV can be significantly enhanced by exogenously applied lactobacilli.

PMID- 18823488
TI  - A randomised comparison of SurePath liquid-based cytology and conventional smear
      cytology in a colposcopy clinic setting.
AB  - OBJECTIVE: The objective of this study was to compare the sensitivity of cervical
      cytology using conventional smears and SurePath liquid-based cytology (LBC).
      DESIGN: Prospective randomised evaluation of diagnostic test. SETTING: A single
      institution colposcopy clinic. POPULATION: Women attending first visit colposcopy
      appointments were offered entry into the study. METHODS: Cervical cytology
      samples from 913 women of age 16-75 years were randomly processed as SurePath LBC
      or conventional smears. Conventional smears were taken for 453 women and a
      SurePath LBC taken for 451 women. Cytology results were correlated with
      colposcopic findings and histology from colposcopic biopsies, treatment and
      follow up. MAIN OUTCOME MEASURES: To compare the sensitivity of SurePath LBC and
      conventional smears for histologically proven abnormality. Other outcome measures
      include a comparison of their sensitivity for high-grade abnormalities and their
      satisfactory rate. RESULTS: Accounting for all randomised samples, there was a
      trend towards improved sensitivity for SurePath LBC (79.1 versus 73.7%, P = 0.1).
      However, excluding unsatisfactory cytology (and samples not taken) eliminated
      this trend; the sensitivity for both LBC and conventional smears for any
      epithelial abnormality was 81%. With a threshold of atypical squamous cells of
      uncertain significance (ASC-US), both SurePath LBC and conventional smears had a
      sensitivity of 92% for high-grade lesions. SurePath LBC was less likely to be
      reported as unsatisfactory (2.7 versus 9.1%, P < 0.0001). CONCLUSIONS: In this
      context, with a threshold of ASC-US, both SurePath LBC and conventional smears
      offer high sensitivity for the detection of CIN2/3, but SurePath LBC is less
      likely to be reported as unsatisfactory.

PMID- 18823489
TI  - Customised birthweight percentiles: does adjusting for maternal characteristics
      matter?
AB  - OBJECTIVE: The objective of this study was to determine whether the improved
      prediction of risk for perinatal mortality obtained with the use of a customised
      birthweight standard can also be obtained with the use of a non-customised but
      intrauterine-based standard. DESIGN: Population-based cohort study. SETTING:
      Sweden. POPULATION: Births in the Swedish Medical Birth Register between 1992 and
      2001 (n = 782 303) with complete data on birthweight, gestational age, sex,
      maternal age, pre-pregnancy body mass index, height, parity, and ethnicity.
      METHODS: We calculated the relative risks (RRs) of stillbirth and early neonatal
      mortality among small-for-gestational-age (SGA) births as established by (1) a
      customised standard, (2) a population standard based on birthweights, and (3) a
      population standard based on a best estimate of intrauterine weights. MAIN
      OUTCOME MEASURES: Stillbirth and early neonatal mortality (<7 days). RESULTS: The
      RRs of stillbirth and early neonatal mortality among SGA births as classified by
      the intrauterine standard were similar to those among SGA births as classified by
      the customised standard and much higher than those among SGA births as classified
      by the birthweight standard. CONCLUSIONS: A non-customised but intrauterine-based
      standard has a similar ability to predict risk for stillbirth and early neonatal
      mortality as a customised birthweight standard. The process of customising
      population weight-for-gestational-age standards to account for maternal
      characteristics does little to improve prediction of perinatal mortality.

PMID- 18823490
TI  - Can excess maternal mortality among women of foreign nationality be explained by
      suboptimal obstetric care?
AB  - OBJECTIVES: To test the hypothesis that the risk of postpartum maternal death in
      France remains significantly higher for women of foreign nationality after
      individual characteristics are taken into account and to examine whether the
      quality of care received by the women who died differs according to nationality.
      DESIGN: A national case-control study. SETTING: Metropolitan France. POPULATION:
      A total of 267 women who died of maternal death from 1996 to 2001 as cases and a
      representative sample (n = 13 186) of women who gave birth in 1998 as controls.
      METHODS: Crude and adjusted odd ratios were calculated with multivariate logistic
      regression, and the quality of care for cases was compared according to
      nationality with chi-square tests or Fisher's exact tests. MAIN OUTCOME MEASURES:
      Odd ratio for postpartum maternal death associated with nationality and quality
      of care. RESULTS: After taking individual characteristics into account, the risk
      of postpartum maternal death was twice as high for foreign women. The odds ratio
      was 5.5 (95% CI: 3.3-9.0) for women from sub-Saharan Africa and 3.3 (95% CI: 1.7
      6.5) for those from Asia, North and South America. There was no significant
      excess risk of postpartum maternal death for the other European and North Africa
      women. The risk of dying from hypertensive disorder or infection was four times
      higher for foreign women. Among women who died, care was more often considered
      not optimal for foreign women (78 versus 57%). CONCLUSIONS: The excess risk of
      postpartum maternal death persisted for foreign women after individual
      characteristics were taken into account and was especially important for some
      nationalities and for some causes of death, primarily hypertensive disorders.
      These results point to an immediate need to pay special attention to early
      enrollment in prenatal care, screening and prenatal management of hypertension,
      especially in women of sub-Saharan African nationality.

PMID- 18823491
TI  - The association of maternal chronic hypertension with perinatal death in male and
      female offspring: a record linkage study of 866,188 women.
AB  - OBJECTIVE: The purpose of this study was to determine whether there is a
      difference, by gender, in perinatal mortality in chronically hypertensive women
      compared with normotensive women. DESIGN: Population-based prospective cohort
      study. SETTING: Sweden. POPULATION: A total of 866,188 women with singleton
      pregnancies registered in the Swedish Medical Birth Registry 1992-2004, of which
      4749 were diagnosed with chronic hypertension. METHODS: Multivariate logistic
      regression analysis was performed. In a first step, we adjusted for maternal
      characteristics and in a second step for mild and severe pre-eclampsia,
      gestational diabetes, placental abruption and small for gestational age. An
      effect modification by gender was included in the model. MAIN OUTCOME MEASURES:
      Odds ratios (OR) for intrauterine death, neonatal death and post-neonatal death
      with respect to gender of offspring. RESULTS: The unadjusted OR of intrauterine
      death was 4.12 (95% CI: 2.84-5.96) and 1.29 (95% CI: 0.67-2.48) for male and
      female offspring, respectively, and of neonatal death, it was 3.45 (95% CI: 2.13
      5.59) and 2.17 (95% CI: 1.08-4.35) for male and female offspring, respectively.
      After multivariate analysis, the OR of intrauterine death was 3.07 (95% CI: 2.12
      4.46) and neonatal death was 2.99 (95% CI: 1.84-4.85) for male offspring. For
      female offspring, the OR of intrauterine death was 0.98 (95% CI: 0.51-1.89) and
      neonatal death was 1.88 (95% CI: 0.93-3.79). CONCLUSION: Mothers with chronic
      hypertension have an increased risk of perinatal mortality of their male
      offspring.

PMID- 18823493
TI  - Previous caesarean and the risk of antepartum stillbirth.

PMID- 18823494
TI  - Advances in the medical management of endometriosis.

PMID- 18823496
TI  - Human amnion-derived mesenchymal stem cells are a potential source for uterine
      stem cell therapy.
AB  - OBJECTIVES: Human amnion is an easy-to-obtain novel source of human mesenchymal
      stem cells, which poses little or no ethical dilemmas. We have previously shown
      that human amnion-derived mesenchymal (HAM) cells exhibit certain mesenchymal
      stem cell-like characteristics with respect to expression of stem cell markers
      and differentiation potentials. MATERIALS AND METHODS: In this study, we further
      characterized HAM cells' potential for in vivo therapeutic application. RESULTS:
      Flow cytometric analyses of HAM cells show that they express several stem cell
      related cell surface markers, including CD90, CD105, CD59, CD49d, CD44 and HLA
      ABC, but not CD45, CD34, CD31, CD106 or HLA-DR. HAM cells at the 10th passage
      showed normal karyotype. More interestingly, the AbdB-like HOXA genes HOXA9,
      HOXA10 and HOXA11 that are expressed in the mesenchyme of the developing female
      reproductive tract and pregnant uteri are also expressed in HAM cells, suggesting
      similarities between these two mesenchymal cell types. Progesterone receptor is
      also highly expressed in HAM cells and expression of genes or proteins in HAM
      cells could be manipulated with the aid of lentivirus technology or cell
      permeable peptides. To test potentials of HAM cells for in vivo application, we
      introduced enhanced green fluorescence protein (EGFP)-expressing HAM cells to
      mice by intrauterine infusion (into uteri) or by intravenous injection (into the
      circulation). Presence of EGFP-expressing cells within the uterine mesenchyme
      after intrauterine infusion or in lungs after intravenous injection was noted
      within 1-4 weeks. CONCLUSIONS: Collectively, these results suggest that HAM cells
      are a potential source of mesenchymal stem cells with therapeutic potential.

PMID- 18823497
TI  - Stem cell antigen 2: a new gene involved in the self-renewal of erythroid
      progenitors.
AB  - OBJECTIVES: Stem cell antigen 2 (SCA2), also known as TSA1 and LY6E, is a
      glycosylphosphatidylinositol-anchored molecule that belongs to the Ly-6 family
      and whose function remains largely unknown. We have previously shown that SCA2 is
      overexpressed in self-renewing avian erythroid progenitors (T2ECs) as opposed to
      differentiating T2ECs. The aim of this study was to define the role of SCA2 in
      the switch between self-renewal and differentiation of erythroid progenitors.
      MATERIALS AND METHODS: We have investigated the cellular processes controlled by
      SCA2 in T2ECs by RNA interference and overexpression approaches. Moreover, we
      have used a SAGE Querying and analysis tools developed in our laboratory, to
      investigate the expression level of SCA2 gene in different human cell types.
      RESULTS: We demonstrate the regulation of SCA2 expression by TGF-beta, a growth
      factor essential for self-renewal of T2ECs. We establish that SCA2 knockdown by
      RNA interference reduced the proliferation and promoted the differentiation of
      T2ECs. In contrast, SCA2 overexpression inhibited differentiation of T2ECs only.
      Furthermore, by using a bioinformatic approach, we found that SCA2 is highly
      expressed in a variety of human cancer cells. We confirmed this result by
      quantitative PCR on human colon and kidney tissues. CONCLUSIONS: Altogether,
      these findings imply that SCA2 may function in a dose-dependent manner to support
      the self-renewal state and that its deregulation might contribute to the
      development of some human cancers.

PMID- 18823498
TI  - Silence of ClC-3 chloride channel inhibits cell proliferation and the cell cycle
      via G/S phase arrest in rat basilar arterial smooth muscle cells.
AB  - OBJECTIVES: Previously, we have found that the ClC-3 chloride channel is involved
      in endothelin-1 (ET-1)-induced rat aortic smooth muscle cell proliferation. The
      present study was to investigate the role of ClC-3 in cell cycle
      progression/distribution and the underlying mechanisms of proliferation.
      MATERIALS AND METHODS: Small interference RNA (siRNA) is used to silence ClC-3
      expression. Cell proliferation, cell cycle distribution and protein expression
      were measured or detected with cell counting, bromodeoxyuridine (BrdU)
      incorporation, Western blot and flow cytometric assays respectively. RESULTS: ET
      1-induced rat basilar vascular smooth muscle cell (BASMC) proliferation was
      parallel to a significant increase in endogenous expression of ClC-3 protein.
      Silence of ClC-3 by siRNA inhibited expression of ClC-3 protein, prevented an
      increase in BrdU incorporation and cell number induced by ET-1. Silence of ClC-3
      also caused cell cycle arrest in G(0)/G(1) phase and prevented the cells'
      progression from G(1) to S phase. Knockdown of ClC-3 potently inhibited cyclin D1
      and cyclin E expression and increased cyclin-dependent kinase inhibitors (CDKIs)
      p27(KIP) and p21(CIP) expression. Furthermore, ClC-3 knockdown significantly
      attenuated phosphorylation of Akt and glycogen synthase kinase-3beta (GSK-3beta)
      induced by ET-1. CONCLUSION: Silence of ClC-3 protein effectively suppressed
      phosphorylation of the Akt/GSK-3beta signal pathway, resulting in down-regulation
      of cyclin D1 and cyclin E, and up-regulation of p27(KIP) and p21(CIP). In these
      BASMCs, integrated effects lead to cell cycle G(1)/S arrest and inhibition of
      cell proliferation.

PMID- 18823499
TI  - A potential role of connexin 43 in epidermal growth factor-induced proliferation
      of mouse embryonic stem cells: involvement of Ca2+/PKC, p44/42 and p38 MAPKs
      pathways.
AB  - OBJECTIVES: The gap junction protein, connexin (Cx), plays an important role in
      maintaining cellular homeostasis and cell proliferation by allowing communication
      between adjacent cells. Therefore, this study has examined the effect of
      epidermal growth factor (EGF) on Cx43 and its relationship to proliferation of
      mouse embryonic stem cells. MATERIALS AND METHODS: Expressions of Cx43, mitogen
      activated protein kinases (MAPKs) and cell cycle regulatory proteins were
      assessed by Western blot analysis. Cell proliferation was assayed with
      [(3)H]thymidine incorporation. Intercellular communication level was measured by
      a scrape loading/dye transfer method. RESULTS: The results showed that EGF
      increased the level of Cx43 phosphorylation in a time- (> or =5 min) and dose- (>
      or =10 ng/mL) dependent manner. Indeed, EGF-induced increase in phospho-Cx43
      level was significantly blocked by either AG 1478 or herbimycin A (tyrosine
      kinase inhibitors). EGF increased Ca(2+) influx and protein kinase C (PKC)
      translocation from the cytosolic compartment to the membrane compartment.
      Moreover, pre-treatment with BAPTA-AM (an intracellular Ca(2+) chelator), EGTA
      (an extracellular Ca(2+) chelator), bisindolylmaleimide I or staurosporine (PKC
      inhibitors) inhibited the EGF-induced phosphorylation of Cx43. EGF induced
      phosphorylation of p38 and p44/42 MAPKs, and this was blocked by SB 203580 (a p38
      MAPK inhibitor) and PD 98059 (a p44/42 MAPK inhibitor), respectively. EGF or
      18alpha-glycyrrhetinic acid (GA; a gap junction inhibitor) increased expression
      levels of the protooncogenes (c-fos, c-jun and c-myc), cell cycle regulatory
      proteins [cyclin D1, cyclin E, cyclin-dependent kinase 2 (CDK2), CDK4 and p-Rb],
      [(3)H]thymidine incorporation and cell number, but decreased expression levels of
      the p21(WAF1/Cip1) and p27(Kip1), CDK inhibitory proteins. Transfection of Cx43
      siRNA also increased the level of [(3)H]thymidine incorporation and cell number.
      EGF, 18alpha-GA or transfection of Cx43 siRNA increased 2-DG uptake and GLUT-1
      protein expression. CONCLUSIONS: EGF-induced phosphorylation of Cx43, which was
      mediated by the Ca(2+)/PKC, p44/42 and p38 MAPKs pathways, partially contributed
      to regulation of mouse embryonic stem cell proliferation.

PMID- 18823501
TI  - What is in store for EJN?

PMID- 18823502
TI  - Embryonic motor activity and implications for regulating motoneuron axonal
      pathfinding in zebrafish.
AB  - Zebrafish embryos exhibit spontaneous contractions of the musculature as early as
      18-19 h post fertilization (hpf) when removed from their protective chorion.
      These movements are likely initiated by early embryonic central nervous system
      activity. We have made the observation that narrowminded mutant embryos
      (hereafter, nrd(-/-)) lack normal embryonic motor output upon dechorionation.
      However, these mutants can swim and respond to tactile stimulation by larval
      stages of development. nrd(-/-) embryos exhibit defects in neural crest
      development, slow muscle development and also lack spinal mechanosensory neurons
      known as Rohon-Beard (RB) neurons. At early developmental stages (i.e. 21-22 hpf)
      and while still in their chorions, nrd siblings (nrd(+/?)) exhibited contractions
      of the musculature at a rate similar to wild-type embryos. Anatomical analysis
      indicated that RB neurons were present in the motile embryos, but absent in the
      non-motile embryos, indicating that the non-motile embryos were nrd(-/-) embryos.
      Further anatomical analysis of nrd(-/-) embryos revealed errors in motoneuron
      axonal pathfinding that persisted into the larval stage of development. These
      errors were reversed when nrd(-/-) embryos were raised in high [K(+)] beginning
      at 21 hpf, indicating that the abnormal axonal phenotypes may be related to a
      lack of depolarizing activity early in development. When activity was blocked
      with tricaine in wild-type embryos, motoneuron phenotypes were similar to the
      motoneuron phenotypes in nrd(-/-) embryos. These results implicate early
      embryonic activity in conjunction with other factors as necessary for normal
      motoneuron development.

PMID- 18823503
TI  - Making mirrors: sensorimotor experience directs activation of the mirror system
      (commentary on Catmur et al.).

PMID- 18823504
TI  - C-reactive protein and coronary heart disease: a critical review.
AB  - Modestly elevated baseline concentrations of C-reactive protein (CRP), the
      classical acute phase protein, are associated with the long-term risk of coronary
      heart disease in general populations, whilst the major acute phase response of
      CRP following myocardial infarction is associated with death and cardiac
      complications. The pathogenic and clinical significance of these associations is
      controversial. Here we critically review the evidence and describe large-scale
      epidemiological studies, novel experiments and possible specific therapies which
      will rigorously inform the debate. We distinguish between the potential
      pathogenicity of high acute phase circulating CRP concentrations in individuals
      with substantial tissue damage and modest but persistent increases in baseline
      values in generally healthy subjects.

PMID- 18823505
TI  - Recent developments in the management of postmenopausal osteoporosis with
      bisphosphonates: enhanced efficacy by enhanced compliance.
AB  - Bisphosphonates are the current mainstay of treatment for postmenopausal
      osteoporosis. Although daily oral dosing is effective, it is associated with poor
      compliance, partly because of the pre and postdose fasting and posture
      requirements. This negatively impacts treatment outcomes, leading to a reduced
      clinical benefit. Improved, yet still suboptimal adherence has been noticed with
      less frequent bisphosphonate dosing e.g. once-weekly and once-monthly oral
      regimens. The recently approved quarterly intravenous (i.v.) injection regimen of
      ibandronate and yearly i.v. infusion of zoledronic acid are attractive options in
      the management of postmenopausal osteoporosis. These regimens may assure
      quarterly and year long compliance.

PMID- 18823506
TI  - Ventilation/Perfusion SPECT for diagnostics of pulmonary embolism in clinical
      practice.
AB  - AIM: The aim of this retrospective study is to illustrate clinical utility and
      impact of pulmonary embolism (PE) diagnostics of up to date Ventilation/Perfusion
      SPECT (V/P (SPECT)) applying holistic interpretation criteria. MATERIAL AND
      METHODS: During a 2-year period 2328 consecutive patients referred to V/P(SPECT)
      for clinically suspected PE were examined. Final diagnosis was established by
      physicians clinically responsible for patient care. To establish the performance
      of V/P(SPECT) negative for PE, patients were followed up by medical records for 6
      months. RESULTS: Ventilation/Perfusion SPECT was feasible in 99% of the patients.
      Data for follow-up were available in 1785 patients (77%). PE was reported in 607
      patients (34%). Normal pattern was described in 420 patients (25%). Pathology
      other than PE such as a pneumonia, left heart failure, obstructive lung disease,
      tumour was described in 724 patients (41%). Report was nondiagnostic in 19
      patients (1%). Six cases were classified as falsely negative because PE was
      diagnosed at follow-up and was fatal in one case. Six cases were classified as
      falsely positive because the clinician decided not to treat. In 608 patients with
      final PE diagnosis, 601 patients had positive V/P(SPECT) (99%). In 1177 patients
      without final PE diagnosis 1153 patients had negative V/P(SPECT) (98%).
      CONCLUSIONS: Holistic interpretation of V/P(SPECT,) yields high negative and
      positive predictive values and only 1% of nondiagnostic findings and was feasible
      in 99% of patients. It is a responsibility and a challenge of nuclear medicine to
      provide optimal care of patients with suspected PE by making V/P(SPECT)
      available.

PMID- 18823507
TI  - Stroke risk might be specifically correlated with the burden of paroxysmal atrial
      fibrillation.

PMID- 18823510
TI  - The cross-cutting edge: striving for symbiosis between medical education research
      and related disciplines.

PMID- 18823511
TI  - Teaching to test or testing to teach?

PMID- 18823512
TI  - Do not adjust your set: the benefits and challenges of test-enhanced learning.

PMID- 18823513
TI  - Neo-colonialism versus sound globalization policy in medical education.

PMID- 18823514
TI  - Test-enhanced learning in medical education.
AB  - CONTEXT: In education, tests are primarily used for assessment, thus permitting
      teachers to assess the efficacy of their curriculum and to assign grades.
      However, research in cognitive psychology has shown that tests can also directly
      affect learning by promoting better retention of information, a phenomenon known
      as the testing effect. COGNITIVE PSYCHOLOGY RESEARCH: Cognitive psychology
      laboratory studies show that repeated testing of information produces superior
      retention relative to repeated study, especially when testing is spaced out over
      time. Tests that require effortful retrieval of information, such as short-answer
      tests, promote better retention than tests that require recognition, such as
      multiple-choice tests. The mnemonic benefits of testing are further enhanced by
      feedback, which helps students to correct errors and confirm correct answers.
      APPLICATION TO MEDICAL EDUCATION: Medical educational research has focused
      extensively on assessment issues. Such assessment research permits the conclusion
      that clinical expertise is founded on a broad fund of knowledge and effective
      memory networks that allow easy access to that knowledge. Test-enhanced learning
      can potentially strengthen clinical knowledge that will lead to improved
      expertise. CONCLUSIONS: Tests should be given often and spaced out in time to
      promote better retention of information. Questions that require effortful recall
      produce the greatest gains in memory. Feedback is crucial to learning from tests.
      Test-enhanced learning may be an effective tool for medical educators to use in
      promoting retention of clinical knowledge.

PMID- 18823515
TI  - Influence of open- and closed-book tests on medical students' learning
      approaches.
AB  - CONTEXT: Two learning approaches are consistently distinguished in the
      literature: deep and surface learning. The deep learning approach is considered
      preferable. Open-book tests are expected to stimulate deep learning and to offer
      a possible way of handling the substantial growth in medical knowledge. In this
      study we test the hypothesis that open-book tests stimulate deep learning more
      than closed-book tests. METHODS: Medical students in Years 2 (n = 423) and 3 (n =
      306) participated in this study. They evaluated their preparation for open- and
      closed-book tests using the test for Deep Information Processing (DIP). This
      questionnaire consists of 24 items divided into three subscales: Critical
      Reading; Broaden One's Context, and Structuring. A paired t-test was used to
      analyse the data. RESULTS: Both cohorts scored significantly higher when
      preparing for closed-book tests for the overall DIP score and on the Broaden
      One's Context and Structuring scales. Year 3 students also scored significantly
      higher on the Critical Reading scale when preparing for closed-book tests. Gender
      differences were found: women used deeper learning approaches than men.
      CONCLUSIONS: Our hypothesis was not supported. In fact, the opposite was found:
      closed-book tests stimulated a deep learning approach more than open-book tests.
      Three possible explanations are: deep learning is particularly necessary for
      remembering and recalling knowledge; students feel more confident when preparing
      for closed-book tests, and students are more motivated to study for closed-book
      tests. The debate on the concept of deep learning in higher education should
      probably be renewed.

PMID- 18823516
TI  - Doctors' perspectives on their innovations in daily practice: implications for
      knowledge building in health care.
AB  - CONTEXT: When individuals adapt their practice in order to solve novel or
      unexpected problems of practice, they are creating new knowledge. This form of
      innovation development is understood as a core competency of adaptive expertise
      and the basis for knowledge building community practice. However, little is known
      about the ways in which this knowledge, produced through daily, innovative
      problem solving, is developed, identified and shared by health care
      professionals. METHODS: Following this line of inquiry, we conducted semi
      structured interviews with a saturation sample of 15 clinical faculty staff at
      the University of Toronto. RESULTS: A grounded theory analysis of the results
      showed that our participants held the view that innovation was focused on
      outcomes, developed through research practice and diffused for adoption in the
      broader community. As a result, their own individual improvements to daily
      practice were excluded from this view of innovation. Furthermore, their
      perceptions of innovation limited participants' engagement in the sort of
      collaborative process that is central to the practice of knowledge-building
      communities. CONCLUSIONS: This research demonstrated that thinking about
      innovation and innovative practice must be changed in order to foster the
      development of knowledge-building communities in medicine.

PMID- 18823517
TI  - Learning not to take it seriously: junior doctors' accounts of error.
AB  - OBJECTIVES: We aimed to investigate experiences of, and responses to, medical
      error amongst junior doctors and to examine the challenges junior doctors face
      and the support they receive. METHODS: We carried out a qualitative study of 38
      randomly selected pre-registration house officers (PRHOs) in 10 hospitals. All 38
      had graduated in 2000 or 2001 from a single medical school. RESULTS: Errors were
      common and sometimes serious. In relation to disclosure and learning from error,
      four main themes emerged: a norm of selective disclosure; the effects of the
      team; individualised blame and responsibility, and the 'learning moment'.
      Trainees reported disclosing errors informally, particularly when teams were seen
      as supportive, but were reluctant to criticize colleagues. Formal reports and
      disclosure to patients were very rare. Patient care was compromised when juniors
      did not access senior help, often when working outside their usual team
      environment. Lack of cooperation between teams and poor continuity of care also
      contributed to errors. Learning was maximised when errors were formally discussed
      and constructive feedback offered. However, both blame and the prioritization of
      reassurance over learning and structured feedback appeared to inhibit reflection
      on the experience of error. CONCLUSIONS: Junior doctors need help to reflect on
      their experiences and to recognise where they may have made mistakes,
      particularly in the contexts of shift-work and fragmented teams. Formal reporting
      systems alone will not facilitate learning from error. Juniors require individual
      clinical supervision from seniors with appropriate training. Such expertise may
      benefit the whole team and the training environment.

PMID- 18823518
TI  - MOR: a simulation-based assessment centre for evaluating the personal and
      interpersonal qualities of medical school candidates.
AB  - CONTEXT: Medical school admissions traditionally rely heavily on cognitive
      variables, with non-cognitive measures assessed through interviews only. In
      recognition of the unsatisfactory reliability and validity of traditional
      interviews, medical schools are increasingly exploring alternative approaches
      that can provide improved measures of candidates' personal and interpersonal
      qualities. METHODS: An innovative assessment centre (MOR [Hebrew acronym for
      'selection for medicine']) was designed to measure candidates' personal and
      interpersonal attributes. Three assessment tools were developed: behavioural
      stations, including encounters with simulated patients and group tasks; an
      autobiographical questionnaire, and a judgement and decision-making
      questionnaire. Candidates were evaluated by trained raters on four qualities:
      interpersonal communication; ability to handle stress; initiative and
      responsibility, and self-awareness. RESULTS: In the years 2004-05, the 588
      medical school candidates with the highest cognitive scores were tested; this
      resulted in a change of approximately 20% in the cohort of accepted students
      compared with previous admission criteria. Internal consistency ranged from 0.80
      to 0.88; inter-rater reliability ranged from 0.62 to 0.77 for the behavioural
      stations and from 0.72 to 0.95 for the questionnaires; test-retest score
      correlation was 0.7. The correlation between candidates' MOR scores and cognitive
      scores approached zero, reflecting the value of MOR in the screening process.
      Feedback from participants indicated that MOR was perceived as fair and
      appropriate for medical school screening. DISCUSSION: MOR is a reliable tool for
      measuring non-cognitive attributes in medical school candidates. It has high
      content and face validity. Furthermore, its implementation conveys the importance
      of maintaining humanist characteristics in the medical profession to students and
      faculty staff.

PMID- 18823519
TI  - Establishing the criterion validity of the Graduate Medical School Admissions
      Test (GAMSAT).
AB  - CONTEXT: This paper examines the criterion validity of the Graduate Medical
      School Admissions Test (GAMSAT), which has been used since 1996 in Australia and
      more recently in the UK and Ireland. The study provides evidence on the extent to
      which GAMSAT, in combination with grade point average (GPA) and interview scores,
      adds value to determining an individual's capability for medical study. The study
      responds to increasing demand for information on the validity of selection
      processes. Criterion validity is important because it helps to empirically
      situate selection tests within their broader contexts by, for instance, providing
      an assurance to educators and the public that test results are valid and add
      value to selection decisions. METHODS: After introducing the rationale and focus
      of the study, the paper summarises the data and research methods, presents
      statistical results and draws conclusions that advance current insight into
      medical school admissions processes. The results are based on data from six
      institutions and 351 students. RESULTS: Analyses of GAMSAT, interview and GPA
      scores show, in summary, that: there are fairly high levels of divergence between
      these three measures; that relationships between the measures and Year 1 marks
      vary across institutions, and that a combination of GAMSAT and GPA scores
      provides the best means of predicting Year 1 performance.

PMID- 18823520
TI  - Changes in performance: a 5-year longitudinal study of participants in a multi
      source feedback programme.
AB  - OBJECTIVES: Multi-source feedback (MSF) enables performance data to be provided
      to doctors from patients, co-workers and medical colleagues. This study examined
      the evidence for the validity of MSF instruments for general practice,
      investigated changes in performance for doctors who participated twice, 5 years
      apart, and determined the association between change in performance and initial
      assessment and socio-demographic characteristics. METHODS: Data for 250 doctors
      included three datasets per doctor from, respectively, 25 patients, eight co
      workers and eight medical colleagues, collected on two occasions. RESULTS: There
      was high internal consistency (alpha > 0.90) and adequate generalisability (Ep(2)
      > 0.70). D study results indicate adequate generalisability coefficients for
      groups of eight assessors (medical colleagues, co-workers) and 25 patient
      surveys. Confirmatory factor analyses provided evidence for the validity of
      factors that were theoretically expected, meaningful and cohesive. Comparative
      fit indices were 0.91 for medical colleague data, 0.87 for co-worker data and
      0.81 for patient data. Paired t-test analysis showed significant change between
      the two assessments from medical colleagues and co-workers, but not between the
      two patient surveys. Multiple linear regressions explained 2.1% of the variance
      at time 2 for medical colleagues, 21.4% of the variance for co-workers and 16.35%
      of the variance for patient assessments, with professionalism a key variable in
      all regressions. CONCLUSIONS: There is evidence for the construct validity of the
      instruments and for their stability over time. Upward changes in performance will
      occur, although their effect size is likely to be small to moderate.

PMID- 18823521
TI  - Specialty-specific multi-source feedback: assuring validity, informing training.
AB  - CONTEXT: The white paper 'Trust, Assurance and Safety: the Regulation of Health
      Professionals in the 21st Century' proposes a single, generic multi-source
      feedback (MSF) instrument in the UK. Multi-source feedback was proposed as part
      of the assessment programme for Year 1 specialty training in histopathology.
      METHODS: An existing instrument was modified following blueprinting against the
      histopathology curriculum to establish content validity. Trainees were also
      assessed using an objective structured practical examination (OSPE). Factor
      analysis and correlation between trainees' OSPE performance and the MSF were used
      to explore validity. All 92 trainees participated and the assessor response rate
      was 93%. Reliability was acceptable with eight assessors (95% confidence interval
      0.38). Factor analysis revealed two factors: 'generic' and 'histopathology'.
      Pearson correlation of MSF scores with OSPE performances was 0.48 (P = 0.001) and
      the histopathology factor correlated more highly (histopathology r = 0.54,
      generic r = 0.42; t = - 2.76, d.f. = 89, P < 0.01). Trainees scored least highly
      in relation to ability to use histopathology to solve clinical problems (mean =
      4.39) and provision of good reports (mean = 4.39). Three of six doctors whose
      means were < 4.0 received free text comments about report writing. There were 83
      forms with aggregate scores of < 4. Of these, 19.2% included comments about
      report writing. RESULTS: Specialty-specific MSF is feasible and achieves
      satisfactory reliability. The higher correlation of the 'histopathology' factor
      with the OSPE supports validity. This paper highlights the importance of
      validating an MSF instrument within the specialty-specific context as, in
      addition to assuring content validity, the PATH-SPRAT (Histopathology-Sheffield
      Peer Review Assessment Tool) also demonstrates the potential to inform training
      as part of a quality improvement model.

PMID- 18823522
TI  - How undergraduate clinical learning climates differ: a multi-method case study.
AB  - CONTEXT: The clinical learning climate affects undergraduate medical students'
      behaviour, satisfaction and success. Most studies predominantly describe aspects
      of the clinical learning climate using quantitative methodologies, such as
      questionnaires. This study aimed to illuminate medical students' perceptions of
      the clinical learning climate, and which factors and their interactions explain
      differences in clinical learning climates. METHODS: We carried out a multi-method
      case study. Twelve departments of obstetrics and gynaecology distributed the
      Postgraduate Hospital Educational Environment Measure (PHEEM), a reliable
      questionnaire measuring the clinical learning environment, among medical
      students. After analysis (using anova and post hoc tests), 14 medical students
      from the highest- and lowest-scoring departments participated in semi-structured
      interviews. We analysed the transcribed recordings using a content analysis
      approach. Researchers agreed on coding and an expert group reached consensus on
      the themes of the analysis. RESULTS: We found a significant difference between
      departments in PHEEM scores. The interviews indicated that department and medical
      student characteristics determine the clinical learning climate. For departments,
      'legitimacy', 'clerkship arrangements' and 'focus on personal development' were
      the main themes. For medical students, 'initial initiatives', 'continuing
      development' and 'clerkship fatigue' were the principal themes. The amount and
      nature of participation played a central role in all themes. CONCLUSIONS:
      Differences between clinical learning climates appear to be related to differing
      approaches to participation among departments. Participation depends on
      characteristics of both departments and students, and the interactions among
      them. The outcomes give valuable clues to how a favourable clinical learning
      climate is shaped.

PMID- 18823523
TI  - Growth of analytical thinking skills over time as measured with the MATCH test.
AB  - CONTEXT: Ber's Comprehensive Integrative Puzzle aims to assess analytical
      clinical thinking in medical students. We developed a paediatric version, the
      MATCH test, in which we added two irrelevant options to each question in order to
      reduce guessing behaviour. We tested its construct validity and studied the
      development of integrative skills over time. METHODS: We administered a test
      (MATCH 1) to subjects from two universities, both with a 6-year medical training
      course. Subjects included 30 students from university 1 who had completed a
      paediatric clerkship in Year 4, 23 students from university 2 who had completed a
      paediatric clerkship in Year 5, 13 students from both universities who had
      completed an advanced paediatric clerkship in Year 6, 28 paediatric residents and
      17 paediatricians. We repeated this procedure using a second test with different
      domains in a new, comparable group of subjects (MATCH 2). RESULTS: Mean MATCH 1
      scores for the respective groups were: Year 4 students: 61.2% (standard deviation
      [SD] 1.3); Year 5 students: 71.3% (SD 1.6); Year 6 students: 76.2% (SD 1.5);
      paediatric residents: 88.5% (SD 0.7), and paediatricians: 92.2% (SD 1.1) (one-way
      ANOVA F = 104.00, P < 0.0001). Students of both universities had comparable
      scores. MATCH 1 and 2 scores were comparable. Cronbach's alpha-values in MATCH 1
      and 2 were 0.92 and 0.91, respectively, for all subjects, and 0.82 and 0.87,
      respectively, for all students. CONCLUSIONS: Analytical clinical thinking
      develops over time, independently of the factual content of the course. This
      implies that shortened medical training programmes could produce less skilled
      graduates.

PMID- 18823524
TI  - Changing unsafe practice is challenging.

PMID- 18823525
TI  - What is the value of good medical education research? A reply to Bligh and Brice.

PMID- 18823526
TI  - Italian network for obesity and cardiovascular disease surveillance: a pilot
      project.
AB  - BACKGROUND: Also in Mediterranean countries, which are considered a low risk
      population for cardiovascular disease (CVD), the increase in body mass index
      (BMI) has become a public health priority. To evaluate the feasibility of a CVD
      and obesity surveillance network, forty General Practitioners (GPs) were engaged
      to perform a screening to assess obesity, cardiovascular risk, lifestyle habits
      and medication use. METHODS: A total of 1,046 women and 1,044 men aged 35-74
      years were randomly selected from GPs' lists stratifying by age decade and
      gender. Anthropometric and blood pressure measurements were performed by GPs
      using standardized methodologies. BMI was computed and categorized in normal
      weight (BMI 18.5-24.9 kg/m2), overweight (BMI 25.0-29.9 kg/m2) and obese (BMI >
      or = 30 kg/m2). Food frequency (per day: fruits and vegetables; per week: meat,
      cheese, fish, pulses, chocolate, fried food, sweet, wholemeal food, rotisserie
      food and sugar drink) and physical activity (at work and during leisure time)
      were investigated through a questionnaire. CVD risk was assessed using the
      Italian CUORE Project risk function. RESULTS: The percentage of missing values
      was very low. Prevalence of overweight was 34% in women and 50% in men;
      prevalence of obesity was 23% in both men and women. Level of physical activity
      was mostly low or very low. BMI was inversely associated with consumption of
      pulses, rotisserie food, chocolate, sweets and physical activity during leisure
      time and directly associated with consumption of meat. Mean value of total
      cardiovascular risk was 4% in women and 11% in men. One percent of women and 16%
      of men were at high cardiovascular risk (> or = 20% in 10 years). Normal weight
      persons were four times more likely to be at low risk than obese persons.
      CONCLUSION: This study demonstrated the feasibility of a surveillance network of
      GPs in Italy focusing on obesity and other CVD risk factors. It also provided
      information on lifestyle habits, such as diet and physical activity.

PMID- 18823527
TI  - A genome-wide association study for late-onset Alzheimer's disease using DNA
      pooling.
AB  - BACKGROUND: Late-onset Alzheimer's disease (LOAD) is an age related
      neurodegenerative disease with a high prevalence that places major demands on
      healthcare resources in societies with increasingly aged populations. The only
      extensively replicable genetic risk factor for LOAD is the apolipoprotein E gene.
      In order to identify additional genetic risk loci we have conducted a genome-wide
      association (GWA) study in a large LOAD case - control sample, reducing costs
      through the use of DNA pooling. METHODS: DNA samples were collected from 1,082
      individuals with LOAD and 1,239 control subjects. Age at onset ranged from 60 to
      95 and Controls were matched for age (mean = 76.53 years, SD = 33), gender and
      ethnicity. Equimolar amounts of each DNA sample were added to either a case or
      control pool. The pools were genotyped using Illumina HumanHap300 and Illumina
      Sentrix HumanHap240S arrays testing 561,494 SNPs. 114 of our best hit SNPs from
      the pooling data were identified and then individually genotyped in the case -
      control sample used to construct the pools. RESULTS: Highly significant
      association with LOAD was observed at the APOE locus confirming the validity of
      the pooled genotyping approach.For 109 SNPs outside the APOE locus, we obtained
      uncorrected p-values </= 0.05 for 74 after individual genotyping. To further test
      these associations, we added control data from 1400 subjects from the 1958 Birth
      Cohort with the evidence for association increasing to 3.4 x 10-6 for our
      strongest finding, rs727153.rs727153 lies 13 kb from the start of transcription
      of lecithin retinol acyltransferase (phosphatidylcholine - retinol O
      acyltransferase, LRAT). Five of seven tag SNPs chosen to cover LRAT showed
      significant association with LOAD with a SNP in intron 2 of LRAT, showing
      greatest evidence of association (rs201825, p-value = 6.1 x 10-7). CONCLUSION: We
      have validated the pooling method for GWA studies by both identifying the APOE
      locus and by observing a strong enrichment for significantly associated SNPs. We
      provide evidence for LRAT as a novel candidate gene for LOAD. LRAT plays a
      prominent role in the Vitamin A cascade, a system that has been previously
      implicated in LOAD.

PMID- 18823529
TI  - The plants, rituals and spells that 'cured' helminthiasis in Sicily.
AB  - BACKGROUND: The author reports on the plants, rituals and spells used against
      worms and the so-called scantu (fright) in some areas of Sicily. The work is
      based on ethnobotanical research carried out, prevalently, between 2002-2006, in
      some areas of Eastern, South-Eastern, North-Central and South-Central Sicily.
      METHODS: This research is based on dialogue. Senior 'healers' were contacted;
      furthermore, doctors, teachers, farmers and in general 'experts' with herbs and
      'magic' rituals. Information was collected about the way the plants of folk
      medicine are prepared. The interviewees were also invited to recite prayers and
      spells against helminthiasis. RESULTS: The author has highlighted the importance
      of how, in some parts of Sicily, some ailments like helminthiasis and other
      correlated pathologies like scantu are 'treated' and, especially within the rural
      social classes, by folk medicine remedies, herbal practises, particular prayers,
      rituals and spells. CONCLUSION: As regards health/illness, it should be noted
      that in the last ten years conventional medicine has provided very satisfactory
      results even resolving potentially mortal pathologies. However, in certain social
      classes, there is no real collaboration between conventional and folk medicine;
      so for some senior citizens, the 'healer' with his rituals and empirical and
      magical herbs is still the person to turn to for the 'cure' of particular
      ailments. Interest in these practises from ancestral heritage in an advanced
      country like Italy, is only relevant if the aim is to recoup a cultural identity
      which is already in decline.It is significant to report a piece: on 14 October
      2007 the news on a well-known national Italian TV channel reported an interview
      with a 94 year-old man from Arbatax (Sardinia) referred to as a 'healer' because
      both his townspeople and others from all over the world go to him for his cures.
      He is not paid except in kind and has been known to cure St. Anthony's fire,
      burns, scalding and marine fungal infections, by smearing his saliva over the
      infected part and reciting 'special words'.

PMID- 18823528
TI  - A multivariate analysis of serum nutrient levels and lung function.
AB  - BACKGROUND: There is mounting evidence that estimates of intakes of a range of
      dietary nutrients are related to both lung function level and rate of decline,
      but far less evidence on the relation between lung function and objective
      measures of serum levels of individual nutrients. The aim of this study was to
      conduct a comprehensive examination of the independent associations of a wide
      range of serum markers of nutritional status with lung function, measured as the
      one-second forced expiratory volume (FEV1). METHODS: Using data from the Third
      National Health and Nutrition Examination Survey, a US population-based cross
      sectional study, we investigated the relation between 21 serum markers of
      potentially relevant nutrients and FEV1, with adjustment for potential
      confounding factors. Systematic approaches were used to guide the analysis.
      RESULTS: In a mutually adjusted model, higher serum levels of antioxidant
      vitamins (vitamin A, beta-cryptoxanthin, vitamin C, vitamin E), selenium,
      normalized calcium, chloride, and iron were independently associated with higher
      levels of FEV1. Higher concentrations of potassium and sodium were associated
      with lower FEV1. CONCLUSION: Maintaining higher serum concentrations of dietary
      antioxidant vitamins and selenium is potentially beneficial to lung health. In
      addition other novel associations found in this study merit further
      investigation.

PMID- 18823530
TI  - Gene products of chromosome 11q and their association with CCND1 gene
      amplification and tamoxifen resistance in premenopausal breast cancer.
AB  - INTRODUCTION: The amplification event occurring at chromosome locus 11q13,
      reported in several different cancers, includes a number of potential oncogenes.
      We have previously reported amplification of one such oncogene, namely CCND1, to
      be correlated with an adverse effect of tamoxifen in premenopausal breast cancer
      patients. Over-expression of cyclin D1 protein, however, confers tamoxifen
      resistance but not a tamoxifen-induced adverse effect. Potentially, co
      amplification of an additional 11q13 gene, with a resulting protein over
      expression, is required to cause an agonistic effect. Moreover, during 11q13
      amplification a deletion of the distal 11q region has been described. In order to
      assess the potential impact of the deletion we examined a selected marker for
      this event. METHOD: Array comparative genomic hybridization analysis was employed
      to identify and confirm changes in the gene expression of a number of different
      genes mapping to the 11q chromosomal region, associated with CCND1 amplification.
      The subsequent protein expression of these candidate genes was then examined in a
      clinical material of 500 primary breast cancers from premenopausal patients who
      were randomly assigned to either tamoxifen or no adjuvant treatment. The protein
      expression was also compared with gene expression data in a subset of 56 breast
      cancer samples. RESULTS: Cortactin and FADD (Fas-associated death domain) over
      expression was linked to CCND1 amplification, determined by fluorescence in situ
      hybridization, but was not associated with a diminished effect of tamoxifen.
      However, deletion of distal chromosome 11q, defined as downregulation of the
      marker Chk1 (checkpoint kinase 1), was associated with an impaired tamoxifen
      response, and interestingly with low proliferative breast cancer of low grade.
      For Pak1 (p21-activated kinase 1) and cyclin D1 the protein expression
      corresponded to the gene expression data. CONCLUSIONS: The results indicate that
      many 11q13 associated gene products are over-expressed in conjunction with cyclin
      D1 but not linked to an agonistic effect of tamoxifen. Finally, the deletion of
      distal 11q, linked to 11q13 amplification, might be an important event affecting
      breast cancer outcome and tamoxifen response.

PMID- 18823531
TI  - Development of behaviour change communication strategy for a vaccination-linked
      malaria control tool in southern Tanzania.
AB  - BACKGROUND: Intermittent preventive treatment of malaria in infants (IPTi) using
      sulphadoxine-pyrimethamine and linked to the expanded programme on immunization
      (EPI) is a promising strategy for malaria control in young children. As evidence
      grows on the efficacy of IPTi as public health strategy, information is needed so
      that this novel control tool can be put into practice promptly, once a policy
      recommendation is made to implement it. This paper describes the development of a
      behaviour change communication strategy to support implementation of IPTi by the
      routine health services in southern Tanzania, in the context of a five-year
      research programme evaluating the community effectiveness of IPTi. METHODS: Mixed
      methods including a rapid qualitative assessment and quantitative health facility
      survey were used to investigate communities' and providers' knowledge and
      practices relating to malaria, EPI, sulphadoxine-pyrimethamine and existing
      health posters. Results were applied to develop an appropriate behaviour change
      communication strategy for IPTi involving personal communication between mothers
      and health staff, supported by a brand name and two posters. RESULTS: Malaria in
      young children was considered to be a nuisance because it causes sleepless
      nights. Vaccination services were well accepted and their use was considered the
      mother's responsibility. Babies were generally taken for vaccination despite
      complaints about fevers and swellings after the injections. Sulphadoxine
      pyrimethamine was widely used for malaria treatment and intermittent preventive
      treatment of malaria in pregnancy, despite widespread rumours of adverse
      reactions based on hearsay and newspaper reports. Almost all health providers
      said that they or their spouse were ready to take SP in pregnancy (96%, 223/242).
      A brand name, key messages and images were developed and pre-tested as behaviour
      change communication materials. The posters contained public health messages,
      which explained the intervention itself, how and when children receive it and
      safety issues. Implementation of IPTi started in January 2005 and evaluation is
      ongoing. CONCLUSION: Behaviour Change Communication (BCC) strategies for health
      interventions must be both culturally appropriate and technically sound. A mixed
      methods approach can facilitate an interactive process among relevant actors to
      develop a BCC strategy.

PMID- 18823533
TI  - Unusual histological presentation in neurofibromas: Two case reports.
AB  - Various histological variants of neurofibroma have been described. The objective
      of this paper is to discuss the unusual histological findings seen in two cases
      of neurofibromas associated with neurofibromatosis type 1 Both cases presented
      with multiple subcutaneous nodules. Surgical excision of the largest nodule was
      done in both the cases. Histological examination of case no.1 revealed a benign
      tumor of the peripheral nerve sheath, of neurofibroma type with presence of mucus
      producing glands. The epithelial component was benign in this case. The second
      case showed presence of rosettes in between areas of typical neurofibroma.

PMID- 18823532
TI  - MetaMQAP: a meta-server for the quality assessment of protein models.
AB  - BACKGROUND: Computational models of protein structure are usually inaccurate and
      exhibit significant deviations from the true structure. The utility of models
      depends on the degree of these deviations. A number of predictive methods have
      been developed to discriminate between the globally incorrect and approximately
      correct models. However, only a few methods predict correctness of different
      parts of computational models. Several Model Quality Assessment Programs (MQAPs)
      have been developed to detect local inaccuracies in unrefined crystallographic
      models, but it is not known if they are useful for computational models, which
      usually exhibit different and much more severe errors. RESULTS: The ability to
      identify local errors in models was tested for eight MQAPs: VERIFY3D, PROSA,
      BALA, ANOLEA, PROVE, TUNE, REFINER, PROQRES on 8251 models from the CASP-5 and
      CASP-6 experiments, by calculating the Spearman's rank correlation coefficients
      between per-residue scores of these methods and local deviations between C-alpha
      atoms in the models vs. experimental structures. As a reference, we calculated
      the value of correlation between the local deviations and trivial features that
      can be calculated for each residue directly from the models, i.e. solvent
      accessibility, depth in the structure, and the number of local and non-local
      neighbours. We found that absolute correlations of scores returned by the MQAPs
      and local deviations were poor for all methods. In addition, scores of PROQRES
      and several other MQAPs strongly correlate with 'trivial' features. Therefore, we
      developed MetaMQAP, a meta-predictor based on a multivariate regression model,
      which uses scores of the above-mentioned methods, but in which trivial parameters
      are controlled. MetaMQAP predicts the absolute deviation (in Angstroms) of
      individual C-alpha atoms between the model and the unknown true structure as well
      as global deviations (expressed as root mean square deviation and GDT_TS scores).
      Local model accuracy predicted by MetaMQAP shows an impressive correlation
      coefficient of 0.7 with true deviations from native structures, a significant
      improvement over all constituent primary MQAP scores. The global MetaMQAP score
      is correlated with model GDT_TS on the level of 0.89. CONCLUSION: Finally, we
      compared our method with the MQAPs that scored best in the 7th edition of CASP,
      using CASP7 server models (not included in the MetaMQAP training set) as the test
      data. In our benchmark, MetaMQAP is outperformed only by PCONS6 and method QA_556
      - methods that require comparison of multiple alternative models and score each
      of them depending on its similarity to other models. MetaMQAP is however the best
      among methods capable of evaluating just single models. We implemented the
      MetaMQAP as a web server available for free use by all academic users at the URL
      https://genesilico.pl/toolkit/

PMID- 18823534
TI  - Diverse histologic appearances in pulmonary mucinous cystic neoplasia: a case
      report.
AB  - INTRODUCTION: Primary pulmonary mucinous cystic neoplasia comprises a group of
      tumors, from benign cystadenoma to mucinous cystadenocarcinoma. CASE
      PRESENTATION: We report a case of primary pulmonary mucinous cystadenocarcinoma
      in a 75-year-old woman who was found to have a right hilar mass on a routine
      chest X-ray. A lobectomy was performed and the resection specimen revealed a
      multicystic mucinous tumor. Microscopically, the tumor was composed of confluent
      mucin-filled cystic spaces lined by columnar mucin-secreting cells which ranged
      from cytologically bland to moderately atypical with 'bronchioloalveolar pattern'
      invasion into the adjacent parenchyma. Immunohistochemically, tumor cells were
      positive diffusely for Cytokeratin 7, and focally for Cytokeratin 20 and Thyroid
      Transcription Factor-1. CONCLUSION: This case highlights the continuous spectrum
      of pulmonary mucinous cystic neoplasia from benign mucinous cystadenoma to
      malignant mucinous cystadenocarcinoma, and the probable existence of a
      'borderline' mucinous cystic tumor. Although molecular data are lacking to
      substantiate progression from benign to malignant in these neoplasms, the
      importance of recognizing the morphologic continuum lies in alerting pathologists
      to thoroughly examine specimens to rule out invasive foci in tumors with
      'borderline' morphology.

PMID- 18823535
TI  - Integrative bioinformatics analysis of transcriptional regulatory programs in
      breast cancer cells.
AB  - BACKGROUND: Microarray technology has unveiled transcriptomic differences among
      tumors of various phenotypes, and, especially, brought great progress in
      molecular understanding of phenotypic diversity of breast tumors. However,
      compared with the massive knowledge about the transcriptome, we have surprisingly
      little knowledge about regulatory mechanisms underling transcriptomic diversity.
      RESULTS: To gain insights into the transcriptional programs that drive tumor
      progression, we integrated regulatory sequence data and expression profiles of
      breast cancer into a Bayesian Network, and searched for cis-regulatory motifs
      statistically associated with given histological grades and prognosis. Our
      analysis found that motifs bound by ELK1, E2F, NRF1 and NFY are potential
      regulatory motifs that positively correlate with malignant progression of breast
      cancer. CONCLUSION: The results suggest that these 4 motifs are principal
      regulatory motifs driving malignant progression of breast cancer. Our method
      offers a more concise description about transcriptome diversity among breast
      tumors with different clinical phenotypes.

PMID- 18823536
TI  - Treatment of branch retinal vein occlusion induced macular edema with
      bevacizumab.
AB  - BACKGROUND: Branch retinal vein occlusion is a frequent cause of visual loss with
      currently insufficient treatment options. We evaluate the effect of Bevacizumab
      (Avastin) treatment in patients with macular edema induced by branch retinal vein
      occlusion. METHODS: Retrospective analysis of 32 eyes in 32 patients with
      fluorescein angiography proven branch retinal vein occlusion, macular edema and
      Bevacizumab treatment. Outcome measures were best corrected visual acuity in
      logMAR and central retinal thickness in OCT. RESULTS: Visual acuity was
      significantly better 4 to 6 weeks after Bevacizumab treatment compared to visual
      acuity prior to treatment (before 0.7 +/- 0.3 and after 0.5 +/- 0.3; mean +/-
      standard deviation; p < 0.01, paired t-test). Gain in visual acuity was
      accompanied by a significant decrease in retinal thickness (454 +/- 117 to 305 +/
      129 microm, p < 0.01, paired t-test). Follow up (170, 27 - 418 days; median,
      range) shows that improvement for both visual acuity and retinal thickness last
      for several months after Bevacizumab use. CONCLUSION: We present evidence that
      intravitreal Bevacizumab is an effective and lasting treatment for macular edema
      after branch retinal vein occlusion.

PMID- 18823537
TI  - Insecticide resistance in Anopheles gambiae from south-western Chad, Central
      Africa.
AB  - BACKGROUND: Indoor residual spraying and insecticide-treated nets (ITN) are
      essential components of malaria vector control in Africa. Pyrethroids are the
      only recommended compounds for nets treatment because they are fast-acting
      insecticides with low mammalian toxicity. However, there is growing concern that
      pyrethroid resistance may threaten the sustainability of ITN scaling-up
      programmes. Here, insecticide susceptibility was investigated in Anopheles
      gambiae sensu lato from an area of large scale ITN distribution programme in
      south-western Chad. METHODS: Susceptibility to 4% DDT, 0.05% deltamethrin, 0.75%
      permethrin, 0.1% bendiocarb and 5% malathion was assessed using the WHO standard
      procedures for adult mosquitoes. Tests were carried out with two to four days
      old, non-engorged female mosquitoes. The An. gambiae Kisumu strain was used as a
      reference. Knockdown effect was recorded every 5 min and mortality scored 24 h
      after exposure. Mosquitoes were identified to species and molecular form by PCR
      RFLP and genotypes at the kdr locus were determined in surviving specimens by Hot
      Oligonucleotide Ligation Assay (HOLA). RESULTS: During this survey, full
      susceptibility to malathion was recorded in all samples. Reduced susceptibility
      to bendiocarb (mortality rate of 96.1%) was found in one sample out of nine
      assayed. Increased tolerance to pyrethroids was detected in most samples (8/9)
      with mortality rates ranging from 70.2 to 96.6% for deltamethrin and from 26.7 to
      96.3% for permethrin. Pyrethroid tolerance was not associated with a significant
      increase of knock-down times. Anopheles arabiensis was the predominant species of
      the An. gambiae complex in the study area, representing 75 to 100% of the
      samples. Screening for kdr mutations detected the L1014F mutation in 88.6% (N =
      35) of surviving An. gambiae sensu stricto S form mosquitoes. All surviving An.
      arabiensis (N = 49) and M form An. gambiae s.s. (N = 1) carried the susceptible
      allele. CONCLUSION: This first investigation of malaria vector susceptibility to
      insecticides in Chad revealed variable levels of resistance to pyrethroid
      insecticides (permethrin and deltamethrin) in most An. gambiae s.l. populations.
      Resistance was associated with the L1014F kdr mutation in the S form of An.
      gambiae s.s.. Alternative mechanisms, probably of metabolic origin are involved
      in An. arabiensis. These results emphasize the crucial need for insecticide
      resistance monitoring and in-depth investigation of resistance mechanisms in
      malaria vectors in Chad. The impact of reduced susceptibility to pyrethroids on
      ITN efficacy should be further assessed.

PMID- 18823538
TI  - Sample size determination for bibliographic retrieval studies.
AB  - BACKGROUND: Research for developing search strategies to retrieve high-quality
      clinical journal articles from MEDLINE is expensive and time-consuming. The
      objective of this study was to determine the minimal number of high-quality
      articles in a journal subset that would need to be hand-searched to update or
      create new MEDLINE search strategies for treatment, diagnosis, and prognosis
      studies. METHODS: The desired width of the 95% confidence intervals (W) for the
      lowest sensitivity among existing search strategies was used to calculate the
      number of high-quality articles needed to reliably update search strategies. New
      search strategies were derived in journal subsets formed by 2 approaches: random
      sampling of journals and top journals (having the most high-quality articles).
      The new strategies were tested in both the original large journal database and in
      a low-yielding journal (having few high-quality articles) subset. RESULTS: For
      treatment studies, if W was 10% or less for the lowest sensitivity among our
      existing search strategies, a subset of 15 randomly selected journals or 2 top
      journals were adequate for updating search strategies, based on each approach
      having at least 99 high-quality articles. The new strategies derived in 15
      randomly selected journals or 2 top journals performed well in the original large
      journal database. Nevertheless, the new search strategies developed using the
      random sampling approach performed better than those developed using the top
      journal approach in a low-yielding journal subset. For studies of diagnosis and
      prognosis, no journal subset had enough high-quality articles to achieve the
      expected W (10%). CONCLUSION: The approach of randomly sampling a small subset of
      journals that includes sufficient high-quality articles is an efficient way to
      update or create search strategies for high-quality articles on therapy in
      MEDLINE. The concentrations of diagnosis and prognosis articles are too low for
      this approach.

PMID- 18823539
TI  - Human embryonic stem cell research, justice, and the problem of unequal
      biological access.
AB  - In 2003, Ruth Faden and eighteen other colleagues argued that a "problem of
      unequal biological access" is likely to arise in access to therapies resulting
      from human embryonic stem cell research. They showed that unless deliberate steps
      are taken in the United States to ensure that the human embryonic stem cell lines
      available to researchers mirrors the genetic diversity of the general population,
      white Americans will likely receive the benefits of these therapies to the
      relative exclusion of minority ethnic groups. Over the past five years the
      problem of unequal biological access has not received much attention from
      politicians, bioethicists and even many researchers in the United States, in
      spite of the widely held belief in the country that there is an obligation to
      prevent and correct ethnic disparities in access to medical care. The purpose of
      this paper is to increase awareness of the problem of unequal biological access
      and of the need to do more than is currently being done to ensure that ethnic
      disparities in access to human embryonic stem cell-based therapies do not arise.
      Specifically, this paper explains why the problem of unequal biological access
      will likely arise in the United States in such a way that white Americans will
      disproportionately receive most of the benefits of the therapies resulting from
      human embryonic stem cell research. It also argues for why there is an obligation
      to prevent these ethnic disparities in access from happening and outlines four
      steps that need to be taken towards meeting this obligation.

PMID- 18823541
TI  - Oral cavity metastasis of renal cell carcinoma: a case report.
AB  - INTRODUCTION: Despite being reported rarely, renal cell carcinoma is the third
      most frequent neoplasm to metastasize to the head and neck region preceded only
      by breast and lung cancer. Little information exists regarding the presentation
      and work-up of metastatic renal cell carcinoma in the oral cavity. CASE
      PRESENTATION: We report the case of a 63-year-old Caucasian man presenting with
      an oral cavity lesion that was painful and that had grown substantially over
      several months. Biopsy resulted in persistent bleeding requiring cautery and
      manual pressure. Immunoperoxidase testing was necessary to make the diagnosis of
      metastatic renal cell carcinoma and rule out other clear cell carcinomas of
      salivary gland origin. CONCLUSION: Metastatic renal cell carcinoma is part of the
      differential diagnosis for patients presenting with a new head or neck lesion in
      the setting of a history of kidney cancer. The physician needs to be prepared for
      the increased risk of bleeding and understand the importance of
      immunohistochemical staining to differentiate between metastatic renal cell
      carcinoma and malignancies of salivary origin. Unfortunately, the prognosis is
      invariably poor in these patients.

PMID- 18823540
TI  - Organogenic nodule development in hop (Humulus lupulus L.): transcript and
      metabolic responses.
AB  - BACKGROUND: Hop (Humulus lupulus L.) is an economically important plant forming
      organogenic nodules which can be used for genetic transformation and
      micropropagation. We are interested in the mechanisms underlying reprogramming of
      cells through stress and hormone treatments. RESULTS: An integrated molecular and
      metabolomic approach was used to investigate global gene expression and metabolic
      responses during development of hop's organogenic nodules. Transcript profiling
      using a 3,324-cDNA clone array revealed differential regulation of 133 unigenes,
      classified into 11 functional categories. Several pathways seem to be determinant
      in organogenic nodule formation, namely defense and stress response, sugar and
      lipid metabolism, synthesis of secondary metabolites and hormone signaling.
      Metabolic profiling using 1H NMR spectroscopy associated to two-dimensional
      techniques showed the importance of metabolites related to oxidative stress
      response, lipid and sugar metabolism and secondary metabolism in organogenic
      nodule formation. CONCLUSION: The expression profile of genes pivotal for energy
      metabolism, together with metabolites profile, suggested that these morphogenic
      structures gain energy through a heterotrophic, transport-dependent and sugar
      degrading anaerobic metabolism. Polyamines and auxins are likely to be involved
      in the regulation of expression of many genes related to organogenic nodule
      formation. These results represent substantial progress toward a better
      understanding of this complex developmental program and reveal novel information
      regarding morphogenesis in plants.

PMID- 18823542
TI  - Relation between Plasmodium falciparum asymptomatic infection and malaria attacks
      in a cohort of Senegalese children.
AB  - BACKGROUND: It is important to establish whether or not the presence of malaria
      parasites in peripheral blood of asymptomatic individuals is a predictor of
      future clinical mild malaria attacks (MMA). The aim of this study was to
      determine how an asymptomatic positive thick blood smear could be related to the
      occurrence of a MMA during the nine following days. METHODS: The study was
      conducted in a cohort of 569 Senegalese children, who were investigated for
      Plasmodium falciparum asymptomatic carriage at two different times of the
      transmission season, the beginning (September) and the end (November). The
      occurrence of MMA was investigated in asymptomatic carriers and non-carriers,
      every three days for nine consecutive days. Survival analysis was performed and
      risk estimates were calculated by Cox proportional hazards model. RESULTS: At the
      beginning of the transmission season, 27.8% (147/529) of the children were
      asymptomatic carriers (ACs) and 5.4% (8/147) of MMA occurred among these, versus
      1% (4/382) among non-carriers (RR = 5.32; IC = [1.56-18.15], p = 0.008). At the
      end of the transmission season, the frequency of asymptomatic carriers was
      similar to that observed at the beginning of the season (31.9%, p = 0.15), but no
      MMA was detected during this period. CONCLUSION: A significant association
      between P. falciparum asymptomatic carriage and the occurrence of MMA at the
      beginning of the transmission season was demonstrated, with a five-fold increase
      in the risk of developing a MMA in ACs. In the context of a possible distribution
      of IPTc in the future, drug strategies may have dramatic consequences due to the
      existence of ACs (both long term and short term), as they seem to play an
      important role in the individual protection to malaria, in the most exposed age
      groups.

PMID- 18823544
TI  - Prevalence and determinants of child maltreatment among high school students in
      Southern China: a large scale school based survey.
AB  - BACKGROUND: Child maltreatment can cause significant physical and psychological
      problems. The present study aimed to investigate the prevalence and determinants
      of child maltreatment in Guangzhou, China, where such issues are often considered
      a taboo subject. METHODS: A school-based survey was conducted in southern China
      in 2005. 24 high schools were selected using stratified random sampling strategy
      based on their districts and bandings. The self-administered validated Chinese
      version of parent-child Conflict Tactics Scale (CTSPC) was used as the main
      assessment tool to measure the abusive experiences encountered by students in the
      previous six months. RESULTS: The response rate of this survey was 99.7%. Among
      the 6592 responding students, the mean age was 14.68. Prevalence of parental
      psychological aggression, corporal punishment, severe and very serve physical
      maltreatment in the past 6 months were 78.3%, 23.2%, 15.1% and 2.8% respectively.
      The prevalence of sexual abuse is 0.6%. The most commonly cited reasons for
      maltreatment included 'disobedience to parents', 'poor academic performance', and
      'quarrelling between parents'. Age, parental education, places of origins and
      types of housing were found to be associated with physical maltreatments whereas
      gender and fathers' education level were associated with sexual abuse.
      CONCLUSION: Though largely unspoken, child maltreatment is a common problem in
      China. Identification of significant determinants in this study can provide
      valuable information for teachers and health professionals so as to pay special
      attention to those at-risk children.

PMID- 18823543
TI  - Perceived needs and satisfaction with care in people with multiple sclerosis: a
      two-year prospective study.
AB  - BACKGROUND: Considering the costs of multiple sclerosis (MS), it is crucial that
      the health-related services supplied are in accordance with needs as they are
      perceived by people with MS (PwMS). Satisfaction with care is related to quality
      of care and can provide health care providers with the means for improvement. The
      aim was to explore the perceived needs and satisfaction with care amongst PwMS
      over a two-year period, also taking sex and disease severity into consideration.
      METHODS: The sample consisted of 219 outpatients at a MS specialist clinic. Data
      on perceived needs and satisfaction with care were collected every six months
      using a questionnaire which included various dimensions of care. The data was
      analysed for the whole sample and on an individual level, as well as in subgroups
      with regard to sex and disease severity. RESULTS: There were no statistically
      significant variations in the proportion of PwMS with perceived needs concerning
      different health-related services during the study period. However, individual
      variations were found with regard to both perceived needs and satisfaction with
      care. Few PwMS perceived a continuous need for a specific service. However, the
      majority perceived a need for rehabilitation, assistive devices, transportation
      service for the disabled, psychosocial support/counselling and information on
      social insurance/vocational rehabilitation at least sometimes. Severe MS was
      associated with a greater perceived need for almost all the services studied and
      women experienced a need for psychosocial support/counselling to a greater extent
      than men. In relation to the different categories of health care staff, PwMS were
      most satisfied with nurses with regard to all dimensions of care. They were least
      satisfied with the availability of psychosocial support/counselling; and
      information about social insurance/vocational rehabilitation. CONCLUSION: Despite
      the large proportion of individuals with mild disease severity in our sample, a
      considerable number of needs were identified of which many, on an individual
      level, varied over time. Key services demanded by PwMS were identified. Also the
      level of satisfaction with care varied and areas with a potential for improvement
      were identified such as the availability of rehabilitation services including an
      increase in the supply of psychosocial support and counselling.

PMID- 18823545
TI  - Physical environmental characteristics and individual interests as correlates of
      physical activity in Norwegian secondary schools: the health behaviour in school
      aged children study.
AB  - BACKGROUND: The school has been identified as a key arena for physical activity
      promotion for young people. Effective change of physical activity behaviour
      requires identification of consistent and modifiable correlates. The study
      explores students' interests in school physical activity and facilities in the
      school environment and examines their associations with students' participation
      in physical activity during recess and their cross-level interaction effect.
      METHODS: This cross-sectional study was based on a national representative sample
      of Norwegian secondary schools and grade 8 students who participated in the
      Health Behaviour in School-aged Children (HBSC) 2005/06 study. The final sample
      comprised 68 schools and 1347 students. Physical environment characteristics were
      assessed through questionnaires completed by the principals, and students'
      physical activity and interests in physical activity were assessed through
      student self-completion questionnaires. RESULTS: Most students were interested in
      more opportunities for physical activity in school. Multilevel logistic
      regression models demonstrated that students attending schools with many
      facilities had 4.49 times (95% Confidence Interval (CI) = 1.93-10.44) higher odds
      of being physically active compared to students in schools with fewer facilities
      when adjusting for socio-economic status, sex and interests in school physical
      activity. Also open fields (Odds Ratio (OR) = 4.31, 95% CI = 1.65-11.28), outdoor
      obstacle course (OR = 1.78, 95% CI = 1.32-2.40), playground equipment (OR = 1.73,
      95% CI = 1.24-2.42) and room with cardio and weightlifting equipment (OR = 1.58,
      95%CI = 1.18-2.10) were associated with increased participation in physical
      activity. Both students' overall interests and the physical facilitation of the
      school environment significantly contributed to the prediction of recess physical
      activity. The interaction term demonstrated that students' interests might
      moderate the effect of facilities on recess physical activity. CONCLUSION: The
      findings support the use of an ecological approach and multilevel analyses in the
      investigation of correlates of physical activity that allows for a broader
      understanding of the influence of and interaction between factors at multiple
      levels on physical activity behaviour. In the promotion of physical activity in
      lower secondary schools, the study suggests that programmes should include a
      focus on environmental facilitation and incorporate strategies to increase
      students' interests for school physical activity.

PMID- 18823546
TI  - The prevalence of pain and disability one year post fracture of the distal radius
      in a UK population: a cross sectional survey.
AB  - BACKGROUND: A fracture of the distal radius is a commonly occurring fracture and
      accounts for a third of all fractures in the elderly. Thus far, one year
      estimates of pain and disability following a fracture of the distal radius have
      been reported on Canadian populations. The primary aim of this study is to
      investigate the prevalence of pain and disability in a UK population one year
      post fracture of the distal radius. METHODS: A cross-sectional survey was
      undertaken, of all subjects suffering a fracture of the distal radius between
      October 2005 and February 2006 in Nottingham, UK. Primary outcomes used were the
      VAS for pain and the DASH for disability. Prevalence of pain and disability were
      calculated and odds ratios presented for associations between demographics, pain
      and disability. RESULTS: 93/264 (35%) subjects responded to the questionnaire. 6
      subjects did not fulfill the inclusion criteria and were excluded from further
      analysis. 11% of subjects reported moderate to very severe pain. 16% of subjects
      reported moderate to very severe disability. Statistically significant
      associations were found between pain medication usage for the wrist fracture and
      moderate to very severe pain (OR 11.20, 95% CI 2.05 - 61.23). Moderate to very
      severe disability was associated with older age (OR 6.53, 95%CI 1.65 - 25.90) and
      pain medication usage for the wrist fracture (OR 4.75, 95% CI 1.38 - 16.37).
      Working was associated with a reduction in risk of moderate to very severe
      disability (OR 0.14, 95% CI 0.03 - 0.67). CONCLUSION: This study demonstrates
      that there are a small proportion of patients who are still suffering moderate to
      very severe pain and disability one year post fracture of the distal radius. The
      study also demonstrates that there are significant associations between
      characteristics of the patients and the level of pain and disability. This
      highlights the need for further research into the most appropriate management of
      these patients in order to reduce this burden of pain and disability,
      particularly as this is a predominantly elderly patient group.

PMID- 18823547
TI  - The small GTPase RhoH is an atypical regulator of haematopoietic cells.
AB  - Rho GTPases are a distinct subfamily of the superfamily of Ras GTPases. The best
      characterised members are RhoA, Rac and Cdc42 that regulate many diverse actions
      such as actin cytoskeleton reorganisation, adhesion, motility as well as cell
      proliferation, differentiation and gene transcription. Among the 20 members of
      that family, only Rac2 and RhoH show an expression restricted to the
      haematopoietic lineage.RhoH was first discovered in 1995 as a fusion transcript
      with the transcriptional repressor LAZ3/BCL6. It was therefore initially named
      translation three four (TTF) but later on renamed RhoH due to its close
      relationship to the Ras/Rho family of GTPases. Since then, RhoH has been
      implicated in human cancer as the gene is subject to somatic hypermutation and by
      the detection of RHOH as a translocation partner for LAZ3/BCL6 or other genes in
      human lymphomas. Underexpression of RhoH is found in hairy cell leukaemia and
      acute myeloid leukaemia.Some of the amino acids that are crucial for GTPase
      activity are mutated in RhoH so that the protein is a GTPase-deficient, so-called
      atypical Rho GTPase. Therefore other mechanisms of regulating RhoH activity have
      been described. These include regulation at the mRNA level and tyrosine
      phosphorylation of the protein's unique ITAM-like motif. The C-terminal CaaX box
      of RhoH is mainly a target for farnesyl-transferase but can also be modified by
      geranylgeranyl-transferase. Isoprenylation of RhoH and changes in subcellular
      localisation may be an additional factor to fine-tune signalling.Little is
      currently known about its signalling, regulation or interaction partners. Recent
      studies have shown that RhoH negatively influences the proliferation and homing
      of murine haematopoietic progenitor cells, presumably by acting as an antagonist
      for Rac1. In leukocytes, RhoH is needed to keep the cells in a resting, non
      adhesive state, but the exact mechanism has yet to be elucidated. RhoH has also
      been implicated as a regulatory molecule in the NFkappaB, PI3 kinase and Map
      kinase pathways. The recent generation of RhoH knockout mice showed a defect in
      thymocyte selection and TCR signalling of thymic and peripheral T-cells. However,
      RhoH-deficient mice did not develop lymphomas or showed obvious defects in
      haematopoiesis.

PMID- 18823548
TI  - Enhancement of presynaptic glutamate release and persistent inflammatory pain by
      increasing neuronal cAMP in the anterior cingulate cortex.
AB  - Both presynaptic and postsynaptic alterations are associated with plastic changes
      of brain circuits, such as learning and memory, drug addiction and chronic pain.
      However, the dissection of the relative contributions of pre- and postsynaptic
      components to brain functions is difficult. We have previously shown peripheral
      inflammation caused both presynaptic and postsynaptic changes and calcium
      stimulated cyclic AMP (cAMP) pathway in the anterior cingulate cortex (ACC) is
      critical in the synaptic plasticity and behavioral sensitization to pain. It
      remains to be elucidated whether presynaptic or postsynaptic modulation by cAMP
      in the ACC could be sufficient for enhancing inflammatory pain. In order to
      address this question, we took advantage of a novel transgenic mouse model,
      heterologously expressing an Aplysia octopamine receptor (Ap oa1). This receptor
      is G protein-coupled and selectively activates the cAMP pathway. We found that
      activation of Ap oa1 by octopamine enhanced glutamatergic synaptic transmission
      in the ACC by increasing presynaptic glutamate release in vitro. Bilateral
      microinjection of octopamine into the ACC significantly facilitated behavioral
      responses to inflammatory pain but not acute pain. The present study provides the
      first evidence linking enhanced presynaptic glutamate release in the ACC to
      behavioral sensitization caused by peripheral inflammation.

PMID- 18823549
TI  - Host immunity in the protective response to vaccination with heat-killed
      Burkholderia mallei.
AB  - BACKGROUND: We performed initial cell, cytokine and complement depletion studies
      to investigate the possible role of these effectors in response to vaccination
      with heat-killed Burkholderia mallei in a susceptible BALB/c mouse model of
      infection. RESULTS: While protection with heat-killed bacilli did not result in
      sterilizing immunity, limited protection was afforded against an otherwise lethal
      infection and provided insight into potential host protective mechanisms. Our
      results demonstrated that mice depleted of either B cells, TNF-alpha or IFN-gamma
      exhibited decreased survival rates, indicating a role for these effectors in
      obtaining partial protection from a lethal challenge by the intraperitoneal
      route. Additionally, complement depletion had no effect on immunoglobulin
      production when compared to non-complement depleted controls infected
      intranasally. CONCLUSION: The data provide a basis for future studies of
      protection via vaccination using either subunit or whole-organism vaccine
      preparations from lethal infection in the experimental BALB/c mouse model. The
      results of this study demonstrate participation of B220+ cells and pro
      inflammatory cytokines IFN-gamma and TNF-alpha in protection following HK
      vaccination.

PMID- 18823550
TI  - Gene expression in BMPR2 mutation carriers with and without evidence of pulmonary
      arterial hypertension suggests pathways relevant to disease penetrance.
AB  - BACKGROUND: While BMPR2 mutation strongly predisposes to pulmonary arterial
      hypertension (PAH), only 20% of mutation carriers develop clinical disease. This
      finding suggests that modifier genes contribute to FPAH clinical expression.
      Since modifiers are likely to be common alleles, this problem is not tractable by
      traditional genetic approaches. Furthermore, examination of gene expression is
      complicated by confounding effects attributable to drugs and the disease process
      itself. METHODS: To resolve these problems, B-cells were isolated, EBV
      immortalized, and cultured from familial PAH patients with BMPR2 mutations,
      mutation positive but disease-free family members, and family members without
      mutation. This allows examination of differences in gene expression without drug
      or disease-related effects. These differences were assayed by Affymetrix array,
      with follow-up by quantitative RT-PCR and additional statistical analyses.
      RESULTS: By gene array, we found consistent alterations in multiple pathways with
      known relationship to PAH, including actin organization, immune function, calcium
      balance, growth, and apoptosis. Selected genes were verified by quantitative RT
      PCR using a larger sample set. One of these, CYP1B1, had tenfold lower expression
      than control groups in female but not male PAH patients. Analysis of
      overrepresented gene ontology groups suggests that risk of disease correlates
      with alterations in pathways more strongly than with any specific gene within
      those pathways. CONCLUSION: Disease status in BMPR2 mutation carriers was
      correlated with alterations in proliferation, GTP signaling, and stress response
      pathway expression. The estrogen metabolizing gene CYP1B1 is a strong candidate
      as a modifier gene in female PAH patients.

PMID- 18823551
TI  - NPHS2 variation in focal and segmental glomerulosclerosis.
AB  - BACKGROUND: Focal and segmental glomerulosclerosis (FSGS) is the most common
      histologic pattern of renal injury seen in adults with idiopathic proteinuria.
      Homozygous or compound heterozygous mutations in the podocin gene NPHS2 are found
      in 10-30% of pediatric cases of steroid resistant nephrosis and/or FSGS. METHODS:
      We studied the spectrum of genetic variation in 371 individuals with
      predominantly late onset FSGS (mean age of onset 25 years) by analysis of DNA
      samples. RESULTS: We identified 15 non-synonymous alleles that changed the amino
      acid sequence in 63 of the subjects screened (17%). Eight of these (p.R138Q,
      p.V180M, p.R229Q, p.E237Q, p.A242V, p.A284V, p.L327F and the frameshift 855-856
      delAA) are alleles previously reported to cause FSGS in either the homozygous or
      compound heterozygous states, while the remaining 7 (p.R10T, p.V127W, p.Q215X,
      p.T232I, p.L270F, p.L312V and the frameshift 397delA) are novel alleles that have
      not been demonstrated previously. Twelve individuals of the 371 (3.2%) screened
      had two likely disease-causing NPHS2 alleles, present in either a homozygous or
      compound heterozygous state. We genotyped the two most common of the non
      synonymous NPHS2 alleles (p.A242V and p.R229Q) identified by resequencing in
      participants from the Nurses' Health Study and also genotyped p.R229Q in 3
      diabetic cohorts. We found that the presence of either of these variants does not
      significantly alter the risk of albuminuria in the Nurses' Health participants,
      nor does p.R229Q associate with "diabetic nephropathy". CONCLUSION: NPHS2
      mutations are a rare cause of FSGS in adults. The most common non-synonymous
      NPHS2 variants, p.R229Q and p.A242V, do not appear to alter the risk of
      proteinuria in the general population nor does p.R229Q associate with measures of
      kidney dysfunction in diabetic individuals. Our results help clarify the
      frequency of FSGS-causing NPHS2 mutations in adults and broaden our understanding
      of the spectrum of NPHS2 mutations that lead to human disease.

PMID- 18823552
TI  - Improvement of quality of life, anxiety and depression after surgery in patients
      with stress urinary incontinence: results of a longitudinal short-term follow-up.
AB  - OBJECTIVE: The objective of this study was to compare the effect of incontinence
      surgery and pelvic floor training on quality of life (QOL), anxiety and
      depression in patients with stress urinary incontinence (SUI). METHODS: In a
      prospective longitudinal study, females with proven SUI were asked to complete a
      set of standardized questionnaires (sociodemographic data sheet, FACT-G, I-QOL,
      HADS) before and eight weeks after treatment. The comparison groups consisted of
      a surgical treatment group and a conservative group that underwent supervised
      pelvic floor training for eight weeks. RESULTS: From the 67 female patients
      included in the study a number of 53 patients completed both assessment time
      points (mean age 57.4, mean years of SUI 7.6). The surgical treatment group
      consisted of 32 patients of which 21 patients received a modified Burch
      colposuspension and 11 patients a tension-free mid-urethral tape suspension. The
      21 patients in the conservative group attended eight once-weekly supervised
      pelvic floor training sessions. After treatment the surgical intervention group
      showed a significantly higher improvement of QOL (FACT-G and I-QOL) and anxiety
      (HADS) than the pelvic floor training group. CONCLUSION: For female patients with
      SUI surgery yielded a better outcome than pelvic floor training with regard to
      quality of life and anxiety.

PMID- 18823553
TI  - Setting up a Paediatric Rapid Access Outpatient Unit: views of general practice
      teams.
AB  - BACKGROUND: Rapid Access Outpatient Units (RAOUs) have been suggested as an
      alternative to hospital inpatient units for the management of some acutely unwell
      children. These units can provide ambulatory care, delivered close to home, and
      may prevent unnecessary hospital admission. There are no qualitative data on the
      views of primary care practitioners regarding these types of facilities. The aim
      of the study was to explore the opinions of primary care practitioners regarding
      a newly established RAOU. METHODS: The RAOU was established locally at a district
      general hospital when inpatient beds were closed and moved to an inpatient
      centre, based six miles away at the tertiary teaching hospital.Qualitative,
      practice based group interviews with primary care practitioners (general
      practitioners (GPs), nurse practitioners and practice nurses) on their
      experiences of the RAOU. The data collection consisted of three practice based
      interviews with 14 participants. The interviews were recorded and transcribed
      verbatim. Thematic content analysis was used to evaluate the data. RESULTS: There
      was positive feedback regarding ease of telephone access for referral, location,
      and the value of a service staffed by senior doctors where children could be
      observed, investigated and discharged quickly. There was confusion regarding the
      referral criteria for the assessment unit and where to send certain children. A
      majority of the practitioners felt the utility of the RAOU was restricted by its
      opening hours. Most participants felt they lacked sufficient information
      regarding the remit and facilities of the unit and this led to some uneasiness
      regarding safety and long term sustainability. CONCLUSION: Practitioners
      considered that the RAOU offered a rapid senior opinion, flexible short term
      observation, quick access to investigations and was more convenient for patients.
      There were concerns regarding opening hours, safety of patients and lack of
      information about the unit's facilities. There was confusion about which children
      should be sent to the unit. This study raises questions regarding policy in
      regard to the organisation of paediatric services. It highlights that when
      establishing alternative services to local inpatient units, continual
      communication and engagement of primary care is essential if the units are to
      function effectively.

PMID- 18823554
TI  - A pre-intervention study of malaria vector abundance in Rio Muni, Equatorial
      Guinea: their role in malaria transmission and the incidence of insecticide
      resistance alleles.
AB  - BACKGROUND: Following the success of the malaria control intervention on the
      island of Bioko, malaria control by the use of indoor residual spraying (IRS) and
      long-lasting insecticide-treated nets (LLITN) was extended to Rio Muni, on the
      mainland part of Equatorial Guinea. This manuscript reports on the malaria
      vectors present and the incidence of insecticide resistant alleles prior to the
      onset of the programme. METHODS: Anopheles mosquitoes were captured daily using
      window traps at 30 sentinel sites in Rio Muni, from December 2006 to July 2007.
      The mosquitoes were identified to species and their sporozoite rates, knockdown
      resistance (kdr) and acetylcholinesterase (AChE) sensitivity measured, to define
      the role of vector species in malaria transmission and their potential
      susceptibility to insecticides. RESULTS: A total of 6,162 Anopheles mosquitoes
      were collected of which 4,808 were morphologically identified as Anopheles
      gambiae s.l., 120 Anopheles funestus, 1,069 Anopheles moucheti, and 165 Anopheles
      nili s.l.. Both M and S molecular forms of Anopheles gambiae s.s. and Anopheles
      melas were identified. Anopheles ovengensis and Anopheles carnevalei were the
      only two members of the An. nili group to be identified. Using the species
      specific sporozoite rates and the average number of mosquitoes per night, the
      number of infective mosquitoes per trap per 100 nights for each species complex
      was calculated as a measure of transmission risk. Both kdr-w and kdr-e alleles
      were present in the S-form of An. gambiae s.s. (59% and 19% respectively) and at
      much lower frequencies in the M-form (9.7% and 1.8% respectively). The kdr-w and
      kdr-e alleles co-occurred in 103 S-form and 1 M-form specimens. No insensitive
      AChE was detected. CONCLUSION: Anopheles gambiae s.s, a member of the Anopheles
      gambiae complex was shown to be the major vector in Rio Muni with the other three
      groups playing a relatively minor role in transmission. The demonstration of a
      high frequency of kdr alleles in mosquito populations before the onset of a
      malaria control programme shows that continuous entomological surveillance
      including resistance monitoring will be of critical importance to ensure the
      chosen insecticide remains effective.

PMID- 18823555
TI  - Utility values for symptomatic non-severe hypoglycaemia elicited from persons
      with and without diabetes in Canada and the United Kingdom.
AB  - OBJECTIVE: To elicit societal and patient utilities associated with diabetic
      symptomatic non-severe hypoglycaemia for three health states: 1) rare
      (quarterly), 2) intermittent (monthly), 3) and frequent (weekly) hypoglycaemia
      episodes. METHODS: Using validated health states, time trade-off utilities were
      elicited from 51 Canadian respondents with diabetes, and 79 respondents in Canada
      and 75 respondents in the United Kingdom (UK) without diabetes. RESULTS AND
      DISCUSSION: Each hypoglycaemic episode was associated with a reduction in utility
      and persons with diabetes consistently reported slightly higher utility values
      than respondents without diabetes. The utility for diabetes without hypoglycaemia
      ranged from 0.88 to 0.97, the mean utility for rare hypoglycaemic events
      (quarterly) ranged between 0.85 and 0.94. The utility for the intermittent state
      (monthly) ranged from 0.77 to 0.90 and from 0.66 to 0.0.83 for the frequent state
      (weekly). Differences were observed between respondents without diabetes in
      Canada and the UK. Using a multivariate linear OLS regression, the estimated
      utilities associated with a single hypoglycaemic event were -0.0033 and -0.0032
      for respondents with diabetes and without diabetes, respectively. CONCLUSION:
      Among respondents with and without diabetes, there was a demonstrable utility
      loss associated with hypoglycaemia. Considering a utility loss of 0.03 as a
      minimum clinically important difference for persons with diabetes, the evidence
      from this study indicates that as low as ten symptomatic non-severe hypoglycaemic
      episodes per year may be of clinical importance and that the importance increases
      with frequency of episodes. Integrating directly elicited utility values such as
      those reported here will improve the quality and applicability of economic
      evaluations of diabetes treatment.

PMID- 18823556
TI  - Country differences in the diagnosis and management of coronary heart disease - a
      comparison between the US, the UK and Germany.
AB  - BACKGROUND: The way patients with coronary heart disease (CHD) are treated is
      partly determined by non-medical factors. There is a solid body of evidence that
      patient and physician characteristics influence doctors' management decisions.
      Relatively little is known about the role of structural issues in the decision
      making process. This study focuses on the question whether doctors' diagnostic
      and therapeutic decisions are influenced by the health care system in which they
      take place. This non-medical determinant of medical decision-making was
      investigated in an international research project in the US, the UK and Germany.
      METHODS: Videotaped patients within an experimental study design were used.
      Experienced actors played the role of patients with symptoms of CHD. Several
      alternative versions were taped featuring the same script with patients of
      different sex, age and social status. The videotapes were shown to 384 randomly
      selected primary care physicians in the three countries under study. The sample
      was stratified on gender and duration of professional experience. Physicians were
      asked how they would diagnose and manage the patient after watching the video
      vignette using a questionnaire with standardised and open-ended questions.
      RESULTS: Results show only small differences in decision making between British
      and American physicians in essential aspects of care. About 90% of the UK and US
      doctors identified CHD as one of the possible diagnoses. Further similarities
      were found in test ordering and lifestyle advice. Some differences between the US
      and UK were found in the certainty of the diagnoses, prescribed medications and
      referral behaviour. There are numerous significant differences between Germany
      and the other two countries. German physicians would ask fewer questions, they
      would order fewer tests, prescribe fewer medications and give less lifestyle
      advice. CONCLUSION: Although all physicians in the three countries under study
      were presented exactly the same patient, some disparities in the diagnostic and
      patient management decisions were evident. Since other possible influences on
      doctors treatment decisions are controlled within the experimental design,
      characteristics of the health care system seem to be a crucial factor within the
      decision making process.

PMID- 18823557
TI  - Molecular architecture of the fruit fly's airway epithelial immune system.
AB  - BACKGROUND: Airway epithelial cells not only constitute a physical barrier, but
      also the first line of defence against airborne pathogens. At the same time, they
      are constantly exposed to reactive oxygen species. Therefore, airway epithelia
      cells have to possess a sophisticated innate immune system and a molecular
      armamentarium to detoxify reactive oxygen species. It has become apparent that
      deregulation of epithelial innate immunity is a major reason for the development
      of chronic inflammatory lung diseases. To elucidate the molecular architecture of
      the innate immune system of airway epithelial cells, we choose the fruit fly
      Drosophila melanogaster as a model, because it has the simplest type of airways,
      consisting of epithelial cells only. Elucidating the structure of the innate
      immune system of this "airway epithelial cell culture" might enable us to
      understand why deregulatory processes in innate immune signalling cascades lead
      to long lasting inflammatory events. RESULTS: All airway epithelial cells of the
      fruit fly are able to launch an immune response. They contain only one functional
      signal transduction pathway that converges onto NF-kappaB factors, namely the IMD
      pathway, which is homologous to the TNF-alpha receptor pathway. Although vital
      parts of the Toll-pathway are missing, dorsal and dif, the NF-kappaB factors
      dedicated to this signalling system, are present. Other pathways involved in
      immune regulation, such as the JNK- and the JAK/STAT-pathway, are completely
      functional in these cells. In addition, most peptidoglycan recognition proteins,
      representing the almost complete collection of pattern recognition receptors, are
      part of the epithelial cells equipment. Potential effector molecules are
      different antimicrobial peptides and lysozymes, but also transferrin that can
      inhibit bacterial growth through iron-depletion. Reactive oxygen species can be
      inactivated through the almost complete armamentarium of enzymatic antioxidants
      that has the fly to its disposal. CONCLUSION: The innate immune system of the
      fly's airway epithelium has a very peculiar organization. A great variety of
      pattern recognition receptors as well as of potential effector molecules are
      conspicuous, whereas signalling presumably occurs through a single NF-kappaB
      activating pathway. This architecture will allow reacting if confronted with
      different bacterial or fungal elicitors by activation of a multitude of
      effectors.

PMID- 18823558
TI  - Preclinical evaluation of dasatinib, a potent Src kinase inhibitor, in melanoma
      cell lines.
AB  - BACKGROUND: Metastatic melanoma is a highly chemotherapy resistant tumour. The
      use of newer targeted therapies alone and in combination with chemotherapy may
      offer new hope of improving response to treatment. Dasatinib, a multi-target
      kinase inhibitor, is currently approved for the treatment of chronic myeloid
      leukaemia and has shown promising results in preclinical studies in a number of
      solid tumours. METHODS: We examined the effects of dasatinib on proliferation,
      chemo-sensitivity, cell cycle arrest, apoptosis, migration and invasion in human
      melanoma cell lines. Expression and activation of Src kinase, FAK and EphA2 were
      also examined in the melanoma cells. RESULTS: Dasatinib inhibited growth of three
      of the five melanoma cell lines. Comparison with sorafenib showed that in these
      three cell lines dasatinib inhibited growth at lower concentrations than
      sorafenib. Dasatinib in combination with the chemotherapy drug temozolomide
      showed greater efficacy than either drug alone. Dasatinib induced cell cycle
      arrest and apoptosis and significantly inhibited cell migration and invasion of
      melanoma cells. Dasatinib inhibition of proliferation was associated with reduced
      phosphorylation of Src kinase, while decreased phosphorylation of FAK was
      implicated in dasatinib-mediated inhibition of migration and invasion in melanoma
      cells. CONCLUSION: Dasatinib has both anti-proliferative and anti-invasive
      effects in melanoma cells and combined with chemotherapy may have clinical
      benefit in the treatment of malignant melanoma.

PMID- 18823559
TI  - Antigen stimulation of peripheral blood mononuclear cells from Mycobacterium
      bovis infected cattle yields evidence for a novel gene expression program.
AB  - BACKGROUND: Bovine tuberculosis (BTB) caused by Mycobacterium bovis continues to
      cause substantial losses to global agriculture and has significant repercussions
      for human health. The advent of high throughput genomics has facilitated large
      scale gene expression analyses that present a novel opportunity for revealing the
      molecular mechanisms underlying mycobacterial infection. Using this approach, we
      have previously shown that innate immune genes in peripheral blood mononuclear
      cells (PBMC) from BTB-infected animals are repressed in vivo in the absence of
      exogenous antigen stimulation. In the present study, we hypothesized that the
      PBMC from BTB-infected cattle would display a distinct gene expression program
      resulting from exposure to M. bovis. A functional genomics approach was used to
      examine the immune response of BTB-infected (n = 6) and healthy control (n = 6)
      cattle to stimulation with bovine tuberculin (purified protein derivative - PPD
      b) in vitro. PBMC were harvested before, and at 3 h and 12 h post in vitro
      stimulation with bovine tuberculin. Gene expression changes were catalogued
      within each group using a reference hybridization design and a targeted
      immunospecific cDNA microarray platform (BOTL-5) with 4,800 spot features
      representing 1,391 genes. RESULTS: 250 gene spot features were significantly
      differentially expressed in BTB-infected animals at 3 h post-stimulation
      contrasting with only 88 gene spot features in the non-infected control animals
      (P < or = 0.05). At 12 h post-stimulation, 56 and 80 gene spot features were
      differentially expressed in both groups respectively. The results provided
      evidence of a proinflammatory gene expression profile in PBMC from BTB-infected
      animals in response to antigen stimulation. Furthermore, a common panel of
      eighteen genes, including transcription factors were significantly expressed in
      opposite directions in both groups. Real-time quantitative reverse transcription
      PCR (qRT-PCR) demonstrated that many innate immune genes, including components of
      the TLR pathway and cytokines were differentially expressed in BTB-infected (n =
      8) versus control animals (n = 8) after stimulation with bovine tuberculin.
      CONCLUSION: The PBMC from BTB-infected animals exhibit different transcriptional
      profiles compared with PBMC from healthy control animals in response to M. bovis
      antigen stimulation, providing evidence of a novel gene expression program due to
      M. bovis exposure.

PMID- 18823560
TI  - The -786T>C promoter polymorphism of the NOS3 gene is associated with prostate
      cancer progression.
AB  - BACKGROUND: There is no biological or epidemiological data on the association
      between NOS3 promoter polymorphisms and prostate cancer. The polymorphisms in the
      promoter region of NOS3 gene may be responsible for variations in the plasma NO,
      which may promote cancer progression by providing a selective growth advantage to
      tumor cells by angiogenic stimulus and by direct DNA damage. METHODS: This study
      aimed evaluating the NOS3 promoter polymorphisms by PCR-SSCP and sequencing,
      associating genotypes and haplotypes with NOS3 expression levels through semi
      quantitative RT-PCR, and with PCA3 mRNA detection, a specific tumor biomarker, in
      the peripheral blood of pre-surgical samples from 177 patients; 83 PCa and 94
      BPH. RESULTS: Three novel SNPs were identified -764A>G, -714G>T and -649G>A in
      the NOS3 gene promoter region, which together with the -786T>C generated four
      haplotypes (N, T, C, A). NOS3 gene expression levels were affected by the -786T>C
      polymorphism, and there was a 2-fold increase in NOS3 levels favored by the
      incorporation of each C allele. NOS3 levels higher than 80% of the constitutive
      gene expression level (B2M) presented a 4-fold increase in PCa occurrence.
      CONCLUSION: The -786T>C polymorphism was the most important promoter alteration
      of the NOS3 gene that may affect the PCa progression, but not its occurrence, and
      the incorporation of the C allele is associated with increased levels of NOS3
      transcripts. The NOS3 transcript levels presented a bimodal behavior in tumor
      development and may be used as a biomarker together with the PCA3 marker for
      molecular staging of the prostate cancer.

PMID- 18823561
TI  - How often do physicians review medication charts on ward rounds?
AB  - BACKGROUND: Prescribing errors are common in hospital settings. Regular review of
      medication charts is recommended as a way to reduce errors but it is not clear
      how often this happens. The aim of this study was to determine the frequency with
      which specialist physicians reviewed medication charts during ward rounds.
      METHODS: An observer noted how often consultant physicians at Auckland City
      Hospital reviewed medication charts during ward rounds. The physicians were not
      aware that they were being observed. RESULTS: Twenty-one physicians were observed
      over a 26 week period. The general physicians reviewed the medication charts on
      77% of occasions (range: 45% - 100%) during routine ward rounds and 65% of the
      time (range: 41% - 80%) on post admission rounds. Subspecialty physicians who did
      not see more than 8 patients on their rounds reviewed medication charts more
      frequently (88%) than those specialties where more than 8 patients were seen on
      average (61%). CONCLUSION: The physicians did not review medication charts on all
      ward rounds and there was considerable variation in how often they did this.
      There is some evidence that the frequency with which charts are reviewed
      decreases as the number of patients seen increases. More efforts should be made
      to encourage regular review of medication charts.

PMID- 18823562
TI  - Cross-species comparison of biological themes and underlying genes on a global
      gene expression scale in a mouse model of colorectal liver metastasis and in
      clinical specimens.
AB  - BACKGROUND: Invasion-related genes over-expressed by tumor cells as well as by
      reacting host cells represent promising drug targets for anti-cancer therapy.
      Such candidate genes need to be validated in appropriate animal models. RESULTS:
      This study examined the suitability of a murine model (CT26/Balb/C) of colorectal
      liver metastasis to represent clinical liver metastasis specimens using a global
      gene expression approach. Cross-species similarity was examined between pure
      liver, liver invasion, tumor invasion and pure tumor compartments through overlap
      of up-regulated genes and gene ontology (GO)-based biological themes on the level
      of single GO-terms and of condensed GO-term families. Three out of four GO-term
      families were conserved in a compartment-specific way between the species:
      secondary metabolism (liver), invasion (invasion front), and immune response
      (invasion front and liver). Among the individual GO-terms over-represented in the
      invasion compartments in both species were "extracellular matrix", "cell
      motility", "cell adhesion" and "antigen presentation" indicating that typical
      invasion related processes are operating in both species. This was reflected on
      the single gene level as well, as cross-species overlap of potential target genes
      over-expressed in the combined invasion front compartments reached up to 36.5%.
      Generally, histopathology and gene expression correlated well as the highest
      single gene overlap was found to be 44% in syn-compartmental comparisons (liver
      versus liver) whereas cross-compartmental overlaps were much lower (e.g. liver
      versus tumor: 9.7%). However, single gene overlap was surprisingly high in some
      cross-compartmental comparisons (e.g. human liver invasion compartment and murine
      tumor invasion compartment: 9.0%) despite little histolopathologic similarity
      indicating that invasion relevant genes are not necessarily confined to
      histologically defined compartments. CONCLUSION: In summary, cross-species
      comparison on a global gene expression scale suggests the validity of an animal
      model representing the human situation. The actual yield of potential target
      genes depends on several variables including the animal model, choice of
      inclusion criteria, inherent species differences and histologic assessment.

PMID- 18823563
TI  - Pharmaceutical induction of ApoE secretion by multipotent mesenchymal stromal
      cells (MSCs).
AB  - BACKGROUND: Apolipoprotein E (ApoE) is a molecular scavenger in the blood and
      brain. Aberrant function of the molecule causes formation of protein and lipid
      deposits or "plaques" that characterize Alzheimer's disease (AD) and
      atherosclerosis. There are three human isoforms of ApoE designated epsilon2,
      epsilon3, and epsilon4. Each isoform differentially affects the structure and
      function of the protein and thus the development of disease. Homozygosity for
      ApoE epsilon4 is associated with atherosclerosis and Alzheimer's disease whereas
      ApoE epsilon2 and epsilon3 tend to be protective. Furthermore, the epsilon2 form
      may cause forms of hyperlipoproteinemia. Therefore, introduction of ApoE epsilon3
      may be beneficial to patients that are susceptible to or suffering from these
      diseases. Mesenchymal stem cells or multipotent mesenchymal stromal cells (MSCs)
      are adult progenitor cells found in numerous tissues. They are easily expanded in
      culture and engraft into host tissues when administered appropriately.
      Furthermore, MSCs are immunosuppressive and have been reported to engraft as
      allogeneic transplants. In our previous study, mouse MSCs (mMSCs) were implanted
      into the brains of ApoE null mice, resulting in production of small amounts of
      ApoE in the brain and attenuation of cognitive deficits. Therefore human MSCs
      (hMSCs) are a promising vector for the administration of ApoE epsilon3 in humans.
      RESULTS: Unlike mMSCs, hMSCs were found not to express ApoE in culture; therefore
      a molecular screen was performed for compounds that induce expression. PPARgamma
      agonists, neural stem cell conditioned medium, osteo-inductive media,
      dexamethasone, and adipo-inductive media (AIM) were tested. Of the conditions
      tested, only AIM or dexamethasone induced sustained secretion of ApoE in MSCs and
      the duration of secretion was only limited by the length of time MSCs could be
      sustained in culture. Upon withdrawal of the inductive stimuli, the ApoE
      secretion persisted for a further 14 days. CONCLUSION: The data demonstrated that
      pre-treatment and perhaps co-administration of MSCs homozygous for ApoE epsilon3
      and dexamethasone may represent a novel therapy for severe instances of AD,
      atherosclerosis and other ApoE-related diseases.

PMID- 18823564
TI  - Mannan-Abeta28 conjugate prevents Abeta-plaque deposition, but increases
      microhemorrhages in the brains of vaccinated Tg2576 (APPsw) mice.
AB  - BACKGROUND: New pre-clinical trials in AD mouse models may help to develop novel
      immunogen-adjuvant configurations with the potential to avoid the adverse
      responses that occurred during the clinical trials with AN-1792 vaccine
      formulation. Recently, we have pursued an alternative immunization strategy that
      replaces QS21 the Th1 type adjuvant used in the AN-1792 clinical trial with a
      molecular adjuvant, mannan that can promote a Th2-polarized immune response
      through interactions with mannose-binding and CD35/CD21 receptors of the innate
      immune system. Previously we established that immunization of wild-type mice with
      mannan-Abeta28 conjugate promoted Th2-mediated humoral and cellular immune
      responses. In the current study, we tested the efficacy of this vaccine
      configuration in amyloid precursor protein (APP) transgenic mice (Tg2576).
      METHODS: Mannan was purified, activated and chemically conjugated to Abeta28
      peptide. Humoral immune responses induced by the immunization of mice with mannan
      Abeta28 conjugate were analyzed using a standard ELISA. Abeta42 and Abeta40
      amyloid burden, cerebral amyloid angiopathy (CAA), astrocytosis, and microgliosis
      in the brain of immunized and control mice were detected using
      immunohistochemistry. Additionally, cored plaques and cerebral vascular
      microhemorrhages in the brains of vaccinated mice were detected by standard
      histochemistry. RESULTS: Immunizations with low doses of mannan-Abeta28 induced
      potent and long-lasting anti-Abeta humoral responses in Tg2576 mice. Even 11
      months after the last injection, the immunized mice were still producing low
      levels of anti-Abeta antibodies, predominantly of the IgG1 isotype, indicative of
      a Th2 immune response. Vaccination with mannan-Abeta28 prevented Abeta plaque
      deposition, but unexpectedly increased the level of microhemorrhages in the
      brains of aged immunized mice compared to two groups of control animals of the
      same age either injected with molecular adjuvant fused with an irrelevant
      antigen, BSA (mannan-BSA) or non-immunized mice. Of note, mice immunized with
      mannan-Abeta28 showed a trend toward elevated levels of CAA in the neocortex and
      in the leptomeninges compared to that in mice of both control groups. CONCLUSION:
      Mannan conjugated to Abeta28 provided sufficient adjuvant activity to induce
      potent anti-Abeta antibodies in APP transgenic mice, which have been shown to be
      hyporesponsive to immunization with Abeta self-antigen. However, in old Tg2576
      mice there were increased levels of cerebral microhemorrhages in mannan-Abeta28
      immunized mice. This effect was likely unrelated to the anti-mannan antibodies
      induced by the immunoconjugate, because control mice immunized with mannan-BSA
      also induced antibodies specific to mannan, but did not have increased levels of
      cerebral microhemorrhages compared with non-immunized mice. Whether these anti
      mannan antibodies increased the permeability of the blood brain barrier thus
      allowing elevated levels of anti-Abeta antibodies entry into cerebral
      perivascular or brain parenchymal spaces and contributed to the increased
      incidence of microhemorrhages remains to be investigated in the future studies.

PMID- 18823565
TI  - Cost effectiveness of preventing falls and improving mobility in people with
      Parkinson disease: protocol for an economic evaluation alongside a clinical
      trial.
AB  - BACKGROUND: Cost of illness studies show that Parkinson disease (PD) is costly
      for individuals, the healthcare system and society. The costs of PD include both
      direct and indirect costs associated with falls and related injuries. METHODS:
      This protocol describes a prospective economic analysis conducted alongside a
      randomised controlled trial (RCT). It evaluates whether physical therapy is more
      cost effective than usual care from the perspective of the health care system.
      Cost effectiveness will be evaluated using a three-way comparison of the cost per
      fall averted and the cost per quality adjusted life year saved across two
      physical therapy interventions and a control group. CONCLUSION: This study has
      the potential to determine whether targetted physical therapy as an adjunct to
      standard care can be cost effective in reducing falls in people with PD. TRIAL
      REGISTRATION: No: ACTRN12606000344594.

PMID- 18823566
TI  - Association of MUTYH Gln324His and APEX1 Asp148Glu with colorectal cancer and
      smoking in a Japanese population.
AB  - BACKGROUND: Genetic polymorphisms of DNA repair enzymes may lead to genetic
      instability and colorectal cancer carcinogenesis. Our objective was to measure
      the interactions between polymorphisms of repair genes and tobacco smoking in
      colorectal cancer. METHODS: The case-control study involved sixty-eight
      colorectal cancer patients and 121 non-cancer controls divided into non-smokers
      and smokers according to pack-years of smoking. The genetic polymorphisms of DNA
      repair enzymes,OGG1 Ser326Cys, MUTYH Gln324His, APEX1 Asp148Glu and XRCC1
      Arg399Gln, were examined using PCR-RFLP. RESULTS: The MUTYH Gln324His showed
      strong significant associations with a risk of colorectal cancer (crude odds
      ratio [OR] 3.30, 95% confidence interval [95%CI] 1.44-7.60, p = 0.005; adjusted
      OR3.53, 95%CI 1.44-8.70, p = 0.006). The ORs for the APEX1 Asp148Glu were
      statistically significant (crude OR 2.69, 95%CI 1.45-4.99, p = 0.002; adjusted OR
      2.33, 95%CI 1.21-4.48, p = 0.011). The ORs for the MUTYH Gln324His and the APEX1
      Asp148Glu were statistically significant for colon cancer (adjusted OR 3.95,
      95%CI 1.28-12.20, p = 0.017 for MUTYH Gln324His ; adjusted OR 3.04, 95%CI 1.38
      6.71, p = 0.006 for APEX1 Asp148Glu). The joint effect of tobacco exposure and
      the MUTYH Gln324His showed a significant association with colorectal cancer risk
      in non-smokers (adjusted OR 4.08, 95%CI 1.22-13.58, p = 0.022) and the APEX1
      Asp148Glu was significantly increased in smokers (adjusted OR 5.02, 95%CI 1.80
      13.99, p = 0.002). However, the distributions of OGG1 Ser326Cys and XRCC1
      Arg399Gln were not associated with a colorectal cancer risk. CONCLUSION: Our
      findings suggest that the MUTYH Gln324His and the APEX1 Asp148Glu constitutes an
      increased risk of colorectal cancer, especially colon cancer. The MUTYH Gln324His
      is strongly associated with colorectal cancer susceptibility in never smoking
      history, whereas the APEX1 Asp148Glu genotype constitutes an increased risk of
      colorectal cancer when accompanied by smoking exposure.

PMID- 18823567
TI  - Development of a loop-mediated isothermal amplification assay for sensitive and
      rapid detection of Vibrio parahaemolyticus.
AB  - BACKGROUND: Vibrio parahaemolyticus is a marine seafood-borne pathogen causing
      gastrointestinal disorders in humans. Thermostable direct hemolysin (TDH) and TDH
      related hemolysin (TRH) are known as major virulence determinants of V.
      parahaemolyticus. Most V. parahaemolyticus isolates from the environment do not
      produce TDH or TRH. Total V. parahaemolyticus has been used as an indicator for
      control of seafood contamination toward prevention of infection. Detection of
      total V. parahaemolyticus using conventional culture- and biochemical-based
      assays is time-consuming and laborious, requiring more than three days. Thus, we
      developed a novel and highly specific loop-mediated isothermal amplification
      (LAMP) assay for the sensitive and rapid detection of Vibrio parahaemolyticus.
      RESULTS: The assay provided markedly more sensitive and rapid detection of V.
      parahaemolyticus strains than conventional biochemical and PCR assays. The assay
      correctly identified 143 V. parahaemolyticus strains, but did not detect 33 non
      parahaemolyticus Vibrio and 56 non-Vibrio strains. Sensitivity of the LAMP assay
      for direct detection of V. parahaemolyticus in pure cultures and in spiked shrimp
      samples was 5.3 x 10(2) CFU per ml/g (2.0 CFU per reaction). The sensitivity of
      the LAMP assay was 10-fold more sensitive than that of the conventional PCR
      assay. The LAMP assay was markedly faster, requiring for amplification 13-22 min
      in a single colony on TCBS agar from each of 143 V. parahaemolyticus strains and
      less than 35 min in spiked shrimp samples. The LAMP assay for detection of V.
      parahaemolyticus required less than 40 min in a single colony on thiosulfate
      citrate bile salt sucrose (TCBS) agar and 60 min in spiked shrimp samples from
      the beginning of DNA extraction to final determination. CONCLUSION: The LAMP
      assay is a sensitive, rapid and simple tool for the detection of V.
      parahaemolyticus and will facilitate the surveillance for control of
      contamination of V. parahaemolyticus in seafood.

PMID- 18823568
TI  - iRefIndex: a consolidated protein interaction database with provenance.
AB  - BACKGROUND: Interaction data for a given protein may be spread across multiple
      databases. We set out to create a unifying index that would facilitate searching
      for these data and that would group together redundant interaction data while
      recording the methods used to perform this grouping. RESULTS: We present a method
      to generate a key for a protein interaction record and a key for each participant
      protein. These keys may be generated by anyone using only the primary sequence of
      the proteins, their taxonomy identifiers and the Secure Hash Algorithm. Two
      interaction records will have identical keys if they refer to the same set of
      identical protein sequences and taxonomy identifiers. We define records with
      identical keys as a redundant group. Our method required that we map protein
      database references found in interaction records to current protein sequence
      records. Operations performed during this mapping are described by a mapping
      score that may provide valuable feedback to source interaction databases on
      problematic references that are malformed, deprecated, ambiguous or unfound. Keys
      for protein participants allow for retrieval of interaction information
      independent of the protein references used in the original records. CONCLUSION:
      We have applied our method to protein interaction records from BIND, BioGrid,
      DIP, HPRD, IntAct, MINT, MPact, MPPI and OPHID. The resulting interaction
      reference index is provided in PSI-MITAB 2.5 format at http://irefindex.uio.no.
      This index may form the basis of alternative redundant groupings based on gene
      identifiers or near sequence identity groupings.

PMID- 18823569
TI  - Transplantation of vascular cells derived from human embryonic stem cells
      contributes to vascular regeneration after stroke in mice.
AB  - BACKGROUND: We previously demonstrated that vascular endothelial growth factor
      receptor type 2 (VEGF-R2)-positive cells induced from mouse embryonic stem (ES)
      cells can differentiate into both endothelial cells (ECs) and mural cells (MCs)
      and these vascular cells construct blood vessel structures in vitro. Recently, we
      have also established a method for the large-scale expansion of ECs and MCs
      derived from human ES cells. We examined the potential of vascular cells derived
      from human ES cells to contribute to vascular regeneration and to provide
      therapeutic benefit for the ischemic brain. METHODS: Phosphate buffered saline,
      human peripheral blood mononuclear cells (hMNCs), ECs-, MCs-, or the mixture of
      ECs and MCs derived from human ES cells were intra-arterially transplanted into
      mice after transient middle cerebral artery occlusion (MCAo). RESULTS:
      Transplanted ECs were successfully incorporated into host capillaries and MCs
      were distributed in the areas surrounding endothelial tubes. The cerebral blood
      flow and the vascular density in the ischemic striatum on day 28 after MCAo had
      significantly improved in ECs-, MCs- and ECs+MCs-transplanted mice compared to
      that of mice injected with saline or transplanted with hMNCs. Moreover, compared
      to saline-injected or hMNC-transplanted mice, significant reduction of the
      infarct volume and of apoptosis as well as acceleration of neurological recovery
      were observed on day 28 after MCAo in the cell mixture-transplanted mice.
      CONCLUSION: Transplantation of ECs and MCs derived from undifferentiated human ES
      cells have a potential to contribute to therapeutic vascular regeneration and
      consequently reduction of infarct area after stroke.

PMID- 18823570
TI  - A systems biology approach to construct the gene regulatory network of systemic
      inflammation via microarray and databases mining.
AB  - BACKGROUND: Inflammation is a hallmark of many human diseases. Elucidating the
      mechanisms underlying systemic inflammation has long been an important topic in
      basic and clinical research. When primary pathogenetic events remains unclear due
      to its immense complexity, construction and analysis of the gene regulatory
      network of inflammation at times becomes the best way to understand the
      detrimental effects of disease. However, it is difficult to recognize and
      evaluate relevant biological processes from the huge quantities of experimental
      data. It is hence appealing to find an algorithm which can generate a gene
      regulatory network of systemic inflammation from high-throughput genomic studies
      of human diseases. Such network will be essential for us to extract valuable
      information from the complex and chaotic network under diseased conditions.
      RESULTS: In this study, we construct a gene regulatory network of inflammation
      using data extracted from the Ensembl and JASPAR databases. We also integrate and
      apply a number of systematic algorithms like cross correlation threshold, maximum
      likelihood estimation method and Akaike Information Criterion (AIC) on time
      lapsed microarray data to refine the genome-wide transcriptional regulatory
      network in response to bacterial endotoxins in the context of dynamic activated
      genes, which are regulated by transcription factors (TFs) such as NF-kappaB. This
      systematic approach is used to investigate the stochastic interaction represented
      by the dynamic leukocyte gene expression profiles of human subject exposed to an
      inflammatory stimulus (bacterial endotoxin). Based on the kinetic parameters of
      the dynamic gene regulatory network, we identify important properties (such as
      susceptibility to infection) of the immune system, which may be useful for
      translational research. Finally, robustness of the inflammatory gene network is
      also inferred by analyzing the hubs and "weak ties" structures of the gene
      network. CONCLUSION: In this study, Data mining and dynamic network analyses were
      integrated to examine the gene regulatory network in the inflammatory response
      system. Compared with previous methodologies reported in the literatures, the
      proposed gene network perturbation method has shown a great improvement in
      analyzing the systemic inflammation.

PMID- 18823571
TI  - Is there a need for a GP consultant at a university hospital?
AB  - BACKGROUND: Patients in hospital can develop complaints unrelated to the
      condition they are admitted for. The treating specialist will then call upon a co
      specialist who is specialized in the clinical picture associated with the new
      complaint. For such a complaint, the GP is usually the first contact, when the
      patient is not in hospital. Normally specialists only encounter patients GPs have
      selected for referral. The risk of the specialist overestimating the predictive
      value of 'unselected' complaints and symptoms of a serious condition is high.
      This may lead to an overuse of diagnostic treatments. Such treatments weigh more
      heavily on the patient, cause inadequate use of hospital facilities and, as a
      consequence, generate higher costs. Because of these considerations, we wished to
      investigate if there is a need for the GP as a consultant for new complaints
      during hospital admittance. METHOD: The files of a random sample of patients who
      had an interdisciplinary consultation during their stay in hospital were judged
      by an expertpanel whether the consultation fitted the expertise of a GP. RESULTS:
      In 28 out of 84 files the consultation fitted the expertise of a GP; most cases
      concerned a specific condition that is not part of the specialist's expertise,
      most frequently dermatological problems. In a minority of cases the specialist is
      confronted with a clinical problem with symptoms of which the cause is not clear,
      for example fever. CONCLUSION: Generally, the consultations concern serious,
      often very complex conditions, i.e. cases that should be assessed by a
      specialist. Nevertheless, the expert panel's judgment of the interdisciplinary
      consultations shows that in more than half of the dermatological cases and in a
      limited number of consultations by a specialist of internal medicine and
      geriatrics the problems fit the GP's expertise. Given the morbidity in academic
      hospitals we suppose that the results of a similar study in a peripheral hospital
      might even show more perspective for a GP consultant. These results offer
      sufficient arguments to start a pilotstudy into the role of a GP consultant in
      hospital.

PMID- 18823572
TI  - [Biology of the Phaenicia sericata fly in different substrata].
AB  - Dipterans of the species Phaenicia sericata were captured and placed in cages in
      order to evaluate their biological cycle and to define the best substratum for
      posture and development of the larvae in controlled temperature and humidity (27
      degrees C e 80% UR). Four decomposing substrata were evaluated: bovine, chicken
      and fish meat as well as bovine liver. No statistical differences were observed
      in the three first substrata and no posture occurred in the liver. The same
      substrata were used for feeding larvae and no interference in the larval cycle
      was observed. The copula occurred five days after the pupation and the posture
      six days after the copula. The average longevity of the adult flies was 37 days
      when they were fed with honey and water. According to these results the
      biological cycle of P. sericata in laboratory was approximately of 51 days.

PMID- 18823573
TI  - Thermal requirements of Dermanyssus gallinae (De Geer, 1778) (Acari:
      Dermanyssidae).
AB  - The thermal requirements for development of Dermanyssus gallinae were studied
      under laboratory conditions at 15, 20, 25, 30 and 35 degrees C, a 12h photoperiod
      and 60-85% RH. The thermal requirements for D. gallinae were as follows.
      Preoviposition: base temperature 3.4 degrees C, thermal constant (k) 562.85
      degree-hours, determination coefficient (R(2)) 0.59, regression equation: Y= 
      0.006035 + 0.001777x. Egg: base temperature 10.60 degrees C, thermal constant (k)
      689.65 degree-hours, determination coefficient (R(2)) 0.94, regression equation:
      Y= -0.015367 + 0.001450x. Larva: base temperature 9.82 degrees C, thermal
      constant (k) 464.91 degree-hours, determination coefficient (R(2)) 0.87,
      regression equation: Y= -0.021123 + 0.002151x. Protonymph: base temperature 10.17
      degrees C, thermal constant (k) 504.49 degree-hours, determination coefficient
      (R(2)) 0.90, regression equation: Y= -0.020152 + 0.001982x. Deutonymph: base
      temperature 11.80 degrees C, thermal constant (k) 501.11 degree-hours,
      determination coefficient (R(2)) 0.99, regression equation: Y= -0.023555 +
      0.001996x. The results obtained showed that 15 to 42 generations of Dermanyssus
      gallinae may occur during the year in the State of Sao Paulo, as estimated based
      on isotherm charts. Dermanyssus gallinae may develop continually in the State of
      Sao Paulo, with a population decrease in the winter. There were differences
      between the developmental stages of D. gallinae in relation to thermal
      requirements.

PMID- 18823574
TI  - [Immune-humoral response of water buffalo (Bubalus bubalis) against Anaplasma
      marginale (Theiler, 1910)].
AB  - The aim of the present study was to analyze the humoral-immune response of water
      buffalo (Bubalus bubalis) naturally infected against Anaplasma marginale. For
      this work, colostrums/milk and blood samples were sequentially collected from
      buffalo cows prior and after partum for a period of 335 days and from buffalo
      calves from birth to 365 days after. The antibodies in the colostrums/milk and
      serum samples of these animals were determined using an ELISA indirect method and
      the data were analyzed as a mean of a group of animals with the matched ages
      during the period of 1999/2000 or individually during the year of 2005. The data
      from animals analyzed in group showed that the antibodies against A. marginale
      were in low concentration (below the cut off point: D.O. = 0.265 and ELISA
      levels, EL < or =3), in the sera of buffalo, during the first 90 and 105 days,
      respectively for cows and calves. Then, the levels of antibodies in the serum
      samples of buffalo calves, slightly raised to above the cut-off point and kept in
      higher levels up to approximately 365 days after birth, indicating active
      acquired immunity. Furthermore, when the animals were individually examined, the
      buffalo cows showed high antibody levels in the colostrums, but low levels in the
      blood stream during the first seven days post-partum, suggesting antibody
      transference from blood to mammary gland. In addition to that, buffalo calves
      showed high antibody levels during the first 24 hours after suckling colostrum,
      indicating a colostral passive immunity. By conclusion, the buffaloes were able
      to arm a humoral immune response against A. marginale and were considered
      reservoir of this parasite.

PMID- 18823575
TI  - [Physiological response of experimental challenge of Ichthyophthirius multifiliis
      (Fouquet, 1876) in jundia (Rhamdia quelen Quoy and Gaimard, 1824) fingerlings
      rather fed with different lipid sources].
AB  - A limiting factor in the early stage of the jundia (Rhamdia quelen Quoy; Gaimard,
      1824) culture is the presence of diseases such as ichthyophthiriasis or "Ich".
      Dietary polyunsaturated fatty acids (PUFAs) have a potent immunomodulatory
      activity; and this activity depend of the fish species, quantity/quality of the
      dietary PUFAS. The aim of this study was evaluate the physiologic response of
      jundia, rather fed diets with different sources of fatty acids when challenge to
      Ich disease. Fingerlings of jundia (7.6+/-0.8g) were fed during seven weeks with
      five diets with a different lipid source: fish, linseed and corn oils. Then, the
      fish were challenged with the Ichthyophthirius multifiliis (Fouquet, 1876). On
      the 5(th) day, the presence of the disease was detected. Survival rate, blood
      samples and infection grade were recorded. Diets affect the survival rate of
      fingerlings, thus fish fed with diet with fish oil showed a higher survival.
      Hematocrit and infestation grade no recorder differences among treatment. The
      differential analysis of white blood cells shows difference. The results point
      out, at first time in jundia, that dietary lipids caused diversity physiologic
      response, this may be represent an opportunity for the disease treatment. New
      studies must be carrying out to deep knowledge found.

PMID- 18823576
TI  - [Helminths of Pampas fox, Pseudalopex gymnocercus (Fischer, 1814) and of Crab
      eating fox, Cerdocyon thous (Linnaeus, 1766) in the South of the State of Rio
      Grande do Sul, Brazil].
AB  - Forty wild canids were captured by live trap at Municipalities of Pedro Osorio
      and Pelotas in Southern of the State of Rio Grande do Sul and they were
      transported to the Parasitology Laboratory at the Universidade Federal de
      Pelotas. After they were posted, segments of intestinal, respiratory and urinary
      tracts and liver were separated and examined. Animal skulls were used for
      taxonomic identification. Of forty wild animals trapped, 22 (55%) were
      Pseudalopex gymnocercus and 22 (55%) Cerdocyon thous. The most prevalent
      nematodes were: Ancylostoma caninum (45.4 in P. gymnocercus and 22.2% in C.
      thous), Molineus felineus (9.9 in P. gymnocercus and 5.6% in C. thous),
      Strongyloides sp. (22.7 in P. gymnocercus and 16.7% in C. thous), Trichuris sp.
      (13.6 in P. gymnocercus and 11.1% in C. thous), and Capillaria hepatica (13.6 in
      P. gymnocercus and 5.5% in C. thous). The trematodes observed were: Alaria alata
      (36.4 in P. gymnocercus and 50.0% in C. thous), and Asthemia heterolecithodes in
      5.6% C. thous. Cestodes were identified as Spirometra sp. (61.1% in C. thous and
      54.5 in P. gymnocercus), Diphyllobothriidae, (81.8 in P. gymnocercus and 77.8% in
      C. thous) and an Acantocephala of the genus Centrorhynchus was also observed in
      5.6% of C. thous only. These results indicated the helminths fauna in wild canids
      from the studied area.

PMID- 18823577
TI  - Comparison of predicted binders in Rhipicephalus (Boophilus) microplus intestine
      protein variants Bm86 Campo Grande strain, Bm86 and Bm95.
AB  - This paper reports the sequence analysis of Bm86 Campo Grande strain comparing it
      with Bm86 and Bm95 antigens from the preparations TickGardPLUS and Gavac,
      respectively. The PCR product was cloned into pMOSBlue and sequenced. The
      secondary structure prediction tool PSIPRED was used to calculate alpha helices
      and beta strand contents of the predicted polypeptide. The hydrophobicity profile
      was calculated using the algorithms from the Hopp and Woods method, in addition
      to identification of potential MHC class-I binding regions in the antigens. Pair
      wise alignment revealed that the similarity between Bm86 Campo Grande strain and
      Bm86 is 0.2% higher than that between Bm86 Campo Grande strain and Bm95 antigens.
      The identities were 96.5% and 96.3% respectively. Major suggestive differences in
      hydrophobicity were predicted among the sequences in two specific regions.

PMID- 18823578
TI  - [Expression and enzymatic activity of glutathione s-transferase in tissues of
      Boophilus microplus females].
AB  - Cellular detoxification and excretion enzymes are important to the maintenance of
      cellular homeostasis. In this work mRNA transcription, protein expression and
      enzymatic activity of Glutathione S-transferases (GSTs), enzymes involved in the
      excretion of endo and xenobiotic compounds were analyzed. These parameters are
      elements believed to protect cells against chemical toxicity and oxidative stress
      in different tissues (salivary gland, ovary and synganglion) from partially
      engorged females and engorged females of Boophilus microplus. The results
      presented showed elevated GST activity in partially engorged females. The
      enzymatic activity decreased during the preoviposition period in engorged
      females. GST mRNA transcription was detected in salivary glands and synganglion
      from partially engorged and engorged females, but not in ovary. The results of
      this work help to elucidate the role of GST in tick development and assist in the
      understanding of the importance of GST in tick females during the preparation for
      oviposition.

PMID- 18823579
TI  - Frequency of antibodies to Babesia bigemina, B. bovis, Anaplasma marginale,
      Trypanosoma vivax and Borrelia burgdorferi in cattle from the Northeastern region
      of the State of Para, Brazil.
AB  - Babesiosis, anaplasmosis, and trypanosomosis are relevant diseases, potentially
      causing morbidity in cattle, leading to economic losses. Borreliosis is import as
      a potential zoonosis. The objective of this study was to determine, by indirect
      enzyme-linked immunosorbent assay (ELISA), the frequency of seropositive cattle
      to Babesia bigemina, B. bovis, Anaplasma marginale, Trypanosoma vivax and
      Borrelia burgdorferi in cattle from the Northeastern region of Para, Brazil. Sera
      samples from 246 female adult cattle from municipalities of Castanhal and Sao
      Miguel do Guama were used. Crude antigens ELISAs were used to detect antibodies
      to all agents, except to A. marginale, to which an indirect ELISA with
      recombinant major surface 1a protein (MSP1a) antigen was used. Overall
      frequencies of seropositive animals were: B. bigemina--99.2%; B. bovis--98.8%; A.
      marginale--68.3%; T. vivax--93.1% and B. burgdorferi--54.9%. The frequencies of
      seropositive cattle to B. bovis and B. bigemina suggest a high rate of
      transmission of these organisms by tick in the studied region, which can be
      classified as enzootically stable to these hemoprotozoans. The low frequency of
      seropositive cattle to A. marginale may be attributed to a lower sensitivity of
      the recombinant antigen ELISA utilized or a distinct rate of inoculation of this
      rickettsia by ticks, as compared with Babesia sp. transmission. The high
      frequency of seropositive cattle to T. vivax indicates that this hemoprotozoan is
      prevalent in herds from the Northeastern region of Para. The rate of animal that
      showed homologues antibodies to B. burgdorferi indicates the presence of the
      tickborne spirochaetal agent in the cattle population in the studied region.

PMID- 18823580
TI  - [Pseudolynchia canariensis (Diptera:Hippoboscidae) on Buteogallus aequinoctialis
      (Ciconiiformes: Accipitridae) in the State of Rio de Janeiro, Brazil].
AB  - The record of Pseudolynchia canariensis on two Rufous Crab-Hawk in situ taken
      care of the Hospital Veterinarian of the RioZoo Foundation. The nineteen
      collected specimens had been identified in the Laboratory of Diptera, Fundacao
      Instituto Oswaldo Cruz. The findings of P. canariensis out natural host (Columba
      livia) it represents a contribution to the studies of the family Hippoboscidae
      considering that it does not have records about native birds of the american
      continent parasitized by P. canariensis.

PMID- 18823581
TI  - Tripanosomatides like Trypanosoma theileri in the cattle tick Boophilus
      microplus.
AB  - Findings of epimastigotes forms of a tripanosomatide is reported in the hemolymph
      of the cattle tick Boophilus microplus in the state of Rio Grande do Sul,
      southern Brazil. Morphological evidences suggest they are similar to Trypanosoma
      theileri, a species described as non pathogenic to cattle, and usually
      transmitted by tabanids.

PMID- 18823582
TI  - [Detection of antibodies against Anaplasma sp. in small ruminants from the semi
      arid region against Pernambuco State, Brazil].
AB  - This paper reports the detection of antibodies against Anaplasma sp. in goats and
      sheep from the semi-arid region from Pernambuco State, Brazil, using an enzyme
      linked immunosorbent assay with recombinant MSP5 of Anaplasma marginale. Sera
      from 243 goats and 68 sheep from Ibimirim municipality were analyzed and
      frequencies of antibodies of 11.93% (29/243) and 16.17% (11/68) were found for
      goats and sheep, respectively. The epidemiological relevance of the findings was
      discussed.

PMID- 18823583
TI  - [Relationship between biomass and parasite density of Mediorhynchus emberizae
      (Acanthocephala: Gigantorhynchidae) parasites of Paroaria dominicana
      (Passeriformes: Emberizidae) of the State of Bahia, Brazil].
AB  - During the study of the metazoan parasites of Paroaria dominicana (Linnaeus,
      1758), eight infrapopulations of Mediorhynchus emberizae (Rudolphi, 1819), were
      collected in the medium third of the small intestine, with parasite intensities
      ranging from one to ten specimens. Differences among the average values of the
      biomass, volume of the eggs, volume of the testicles and the parasite density of
      the infrapopulations were statistically tested in order to detect variations of
      these parameters in function of parasite density. Was observed that the
      acanthocephalans biomass increased with the volume of the intestine and also that
      the parasite density increased with the parasite intensity in the
      infrapopulations. It was verified that the increase of the parasite intensity was
      accompanied by the decrease of the mean biomass of the parasites. Decrease of the
      volume of the eggs was verified with the increase of the density and of the
      parasite intensity. The results of the present work could suggested the
      occurrence of density-dependent factors and the decrease of testicles volume and
      the biomass of the males with the increase of the parasite density in the
      infrapopulations of M. emberizae in the intestine of P. dominicana.

PMID- 18823584
TI  - Biomarkers for the lung cancer diagnosis and their advances in proteomics.
AB  - Over a last decade, intense interest has been focused on biomarker discovery and
      their clinical uses. This interest is accelerated by the completion of human
      genome project and the progress of techniques in proteomics. Especially, cancer
      biomarker discovery is eminent in this field due to its anticipated critical role
      in early diagnosis, therapy guidance, and prognosis monitoring of cancers. Among
      cancers, lung cancer, one of the top three major cancers, is the one showing the
      highest mortality because of failure in early diagnosis. Numerous potential DNA
      biomarkers such as hypermethylations of the promoters and mutations in K-ras,
      p53, and protein biomarkers; carcinoembryonic antigen (CEA), CYFRA21-1, plasma
      kallikrein B1 (KLKB1), Neuron-specific enolase, etc. have been discovered as lung
      cancer biomarkers. Despite extensive studies thus far, few are turned out to be
      useful in clinic. Even those used in clinic do not show enough sensitivity,
      specificity and reproducibility for general use. This review describes what the
      cancer biomarkers are for, various types of lung cancer biomarkers discovered at
      present and predicted future advance in lung cancer biomarker discovery with
      proteomics technology.

PMID- 18823585
TI  - Tissue proteomics for cancer biomarker development: laser microdissection and 2D
      DIGE.
AB  - Novel cancer biomarkers are required to achieve early diagnosis and optimized
      therapy for individual patients. Cancer is a disease of the genome, and tumor
      tissues are a rich source of cancer biomarkers as they contain the functional
      translation of the genome, namely the proteome. Investigation of the tumor tissue
      proteome allows the identification of proteomic signatures corresponding to
      clinico-pathological parameters, and individual proteins in such signatures will
      be good biomarker candidates. Tumor tissues are also a rich source for plasma
      biomarkers, because proteins released from tumor tissues may be more cancer
      specific than those from non-tumor cells. Two-dimensional difference gel
      electrophoresis (2D-DIGE) with novel ultra high sensitive fluorescent dyes (CyDye
      DIGE Fluor satulation dye) enables the efficient protein expression profiling of
      laser-microdissected tissue samples. The combined use of laser microdissection
      allows accurate proteomic profiling of specific cells in tumor tissues. To
      develop clinical applications using the identified biomarkers, collaboration
      between research scientists, clinicians and diagnostic companies is essential,
      particularly in the early phases of the biomarker development projects. The
      proteomics modalities currently available have the potential to lead to the
      development of clinical applications, and channeling the wealth of produced
      information towards concrete and specific clinical purposes is urgent.

PMID- 18823586
TI  - Acrolein, the toxic endogenous aldehyde, induces neurofilament-L aggregation.
AB  - Acrolein is a highly reactive by product of lipid peroxidation and individuals
      with neurodegenerative disorders have been shown to contain elevated
      concentrations of this molecule in the brain. In the present study, we examined
      the pattern of neurofilament-L (NF-L) modification elicited by acrolein. When NF
      L was incubated with acrolein, protein aggregation occurred in a acrolein
      concentration-dependent manner. Exposure of NF-L to acrolein also led to the
      generation of protein carbonyl compounds. Through the addition of free radical
      scavengers we observed a significant decrease in acrolein-mediated NF-L
      aggregation. These results indicate that free radicals may be involved in the
      modification of NF-L by acrolein. In addition, dityrosine crosslink formation was
      observed in acrolein-mediated NF-L aggregates and these aggregates displayed
      thioflavin T reactivity, reminiscent of amyloid. This study suggests that
      acrolein-mediated NF-L aggregation might be closely related to oxidative
      reactions, thus these reactions may play a critical role in neurodegenerative
      diseases.

PMID- 18823587
TI  - An anti-viral peptide derived from the preS1 surface protein of hepatitis B
      virus.
AB  - The preS1 surface protein of the hepatitis B virus (HBV) is a key factor involved
      in initial viral entry into hepatocytes. It has been long postulated that an anti
      HBV effect should be achievable using peptide fragments of the preS1. Recent
      reports demonstrated that several preS1-derived lipo-peptides in genotype D HBV
      exhibit nano to picomolar inhibitory activity against HBV infection. In this
      study, an acylated analog of a preS1 fragment, a 21-residue lipo-peptide (named
      7524 BVS7) with a sequence of palmitoyl-GMGTNLSVPNPLGFFPDHQLDC-NH2, from genotype
      C HBV was produced base upon a previous structural study and was shown potently
      inhibits HBV infection with an IC(50) of approximately 20 nM.

PMID- 18823588
TI  - Arabidopsis nucleoside diphosphate kinase-2 as a plant GTPase activating protein.
AB  - Nucleoside diphosphate kinase (NDPK) is involved in multiple signaling pathways
      in mammalian systems, including G-protein signaling. Arabidopsis NDPK2, like its
      mammalian counterparts, is multifunctional despite its initial discovery
      phytochrome-interacting protein. This similarity raises the possibility that
      NDPK2 may play a role in G-protein signaling in plants. In the present study, we
      explore the potential relationship between NDPK2 and the small G proteins, Pra2
      and Pra3, as well as the heterotrimeric G protein, GPA1. We report a physical
      interaction between NDPK2 and these small G proteins, and demonstrate that NDPK2
      can stimulate their GTPase activities. Our results suggest that NDPK2 acts as a
      GTPase-activating protein for small G proteins in plants. We propose that NDPK2
      might be a missing link between the phytochromemediated light signaling and G
      protein-mediated signaling.

PMID- 18823589
TI  - Fine localization of a new cataract locus, Kec, on mouse chromosome 14 and
      exclusion of candidate genes as the gene that causes cataract in the Kec mouse.
AB  - A mouse with cataract, Kec, was generated from N-ethyl-N-nitrosourea (ENU)
      mutagenesis. Cataract in the Kec mouse was observable at about 5 weeks after
      birth and this gradually progressed to become completely opaque by 12 weeks.
      Dissection microscopy revealed that vacuoles with a radial or irregular shape
      were located primarily in the cortex of the posterior and equatorial regions of
      the lens. At the late stage, the lens structure was distorted, but not ruptured.
      This cataract phenotype was inherited in an autosomal recessive manner. We
      performed a genetic linkage analysis using 133 mutant and 67 normal mice produced
      by mating Kec mutant (BALB/c) and F1 (C57BL/6 x Kec) mice. The Kec locus was
      mapped to the 3 cM region encompassed by D14Mit34 and D14Mit69. In addition we
      excluded coding sequences of 9 genes including Rcbtb2, P2ry5, Itm2b, Med4,
      Nudt15, Esd, Lcp1, Slc25a30, and 2810032E02Rik as the candidate gene that causes
      cataract in the Kec mouse.

PMID- 18823590
TI  - Taurine protects the antioxidant defense system in the erythrocytes of cadmium
      treated mice.
AB  - The present study was undertaken to investigate the protective role of taurine (2
      aminoethanesulfonic acid) against cadmium (Cd) induced oxidative stress in murine
      erythrocytes. Cadmium chloride (CdCl(2)) was chosen as the source of Cd.
      Experimental animals were treated with either CdCl(2) alone or taurine, followed
      by Cd exposure. Cd intoxication reduced hemoglobin content and the intracellular
      Ferric Reducing/Antioxidant Power of erythrocytes, along with the activities of
      antioxidant enzymes, glutathione content, and total thiols. Conversely,
      intracellular Cd content, lipid peroxidation, protein carbonylation, and
      glutathione disulphides were significantly enhanced in these cells. Treatment
      with taurine before Cd intoxication prevented the toxin-induced oxidative
      impairments in the erythrocytes of the experimental animals. Overall, the results
      suggest that Cd could cause oxidative damage in murine erythrocytes and that
      taurine may play a protective role in reducing the toxic effects of this
      particular metal.

PMID- 18823591
TI  - Expression and localization of the spermatogenesis-related gene, Znf230, in mouse
      testis and spermatozoa during postnatal development.
AB  - Znf230, the mouse homologue of the human spermatogenesis-related gene, ZNF230,
      has been cloned by rapid amplification of cDNA ends (RACE). This gene is
      expressed predominantly in testis, but its expression in different testicular
      cells and spermatogenic stages has not been previously analyzed in detail. In the
      present study, the cellular localization of the Znf230 protein in mouse testis
      and epididymal spermatozoa was determined by RT-PCR, immunoblotting,
      immunohistochemistry and immunofluorescence. It is primarily expressed in the
      nuclei of spermatogonia and subsequently in the acrosome system and the entire
      tail of developing spermatids and spermatozoa. The results indicate that Znf230
      may play an important role in mouse spermatogenesis, including spermatogenic cell
      proliferation and sperm maturation, as well as motility and fertilization.

PMID- 18823592
TI  - Differentially expressed genes in Penaeus monodon hemocytes following infection
      with yellow head virus.
AB  - A cDNA microarray composed of 2,028 different ESTs from two shrimp species,
      Penaeus monodon and Masupenaeus japonicus, was employed to identify yellow head
      virus (YHV)-responsive genes in hemocytes of P. monodon. A total of 105
      differentially expressed genes were identified and grouped into five different
      clusters according to their expression patterns. One of these clusters, which
      comprised five genes including cathepsin L-like cysteine peptidase, hypothetical
      proteins and unknown genes, was of particular interest because the transcripts
      increased rapidly (< or = 0.25 hours) and reached high expression levels in
      response to YHV injection. Microarray data were validated by realtime RT-PCR
      analyses of selected differentially expressed transcripts. In addition,
      comparative analysis of the hemocyte transcription levels of three of these genes
      between surviving and non-surviving shrimp revealed significantly higher
      expression levels in surviving shrimp.

PMID- 18823593
TI  - The unique role of domain 2A of the hepatitis A virus precursor polypeptide P1-2A
      in viral morphogenesis.
AB  - The initial step during assembly of the hepatitis A virus particle is driven by
      domain 2A of P1-2A, which is the precursor of the structural proteins. The
      proteolytic removal of 2A from particulate VP1-2A by an as yet unknown host
      enzyme presumably terminates viral morphogenesis. Using a genetic approach, we
      show that a basic amino acid residue at the C-terminus of VP1 is required for
      efficient particle assembly and that host proteases trypsin and cathepsin L
      remove 2A from hepatitis A virus particles in vitro. Analyses of insertion
      mutants in the C-terminus of 2A reveal that this part of 2A is important for
      liberation of P1-2A from the polyprotein. The data provide the first evidence
      that the VP1/2A junction is involved in both viral particle assembly and
      maturation and, therefore, seems to coordinate the first and last steps in viral
      morphogenesis.

PMID- 18823594
TI  - [Long live the case report].

PMID- 18823595
TI  - [Telemedical pre-hospital diagnosis of a patient with thoracic aortic
      dissection].
AB  - Thoracic aortic dissection is a life-threatening emergency that must be met and
      surmounted immediately to increase survival. In this case, telemedicine involving
      ECG and GSM-based communication between the patient in the ambulance and the
      centre doctor was used to obtain remote pre-hospital suspicion of aorta
      dissection. Thus, the ambulance was re-routed directly to a specialized unit
      where the diagnosis was confirmed and immediate and successful surgical treatment
      was performed. Telemedicine allowing direct communication between the patient and
      the doctor is recommended.

PMID- 18823596
TI  - [Bicipitoradial bursitis].
AB  - Bicipitoradial bursitis is a rare pathological condition of the elbow and is seen
      as a distension of the bicipitoradial bursa in the cubital fossa. The bursa is
      located at the insertion of the distal biceps tendon and the role of this bursa
      is to reduce friction between the biceps tendon and the tuberosity of the radius.
      Most often, enlargement or bursitis results from repetitive mechanical trauma. In
      the present case report, we describe the condition in a 71-year-old woman using
      both MR and ultra sound scanning.

PMID- 18823597
TI  - [Acute ischemic proctitis following an epileptic attack].
AB  - Acute ischemic proctitis is a rare diagnosis mainly because the rectum is
      supplied by an extensive arterial network. Consequently, in more than 90% of
      patients with ischemic colitis the rectum is spared. Previously reported cases
      are related to severe vascular insufficiency of the rectal circulation caused by
      systemic atherosclerosis, usually following aortic or aortoiliac operations. We
      report one case of acute ischemic proctitis following an epileptic attack.

PMID- 18823598
TI  - [Syphilis--''to be or not to be"].
AB  - Syphilis has increased in Denmark and this "great imitator" disease is easily
      overlooked. Two case stories are presented; one case illustrates how a patient
      with classical symptoms of secondary syphilis was overlooked by doctors of
      several specialities for one year, and the other case is of a patient with a
      lesion on the penis presenting clinically, serologically and histologically as a
      syphilitic chancre, but it proved to be a rare chronic inflammatory condition
      known as a pseudotumor. It is emphasized that doctors in all specialities should
      increase their awareness of this disease.

PMID- 18823599
TI  - [The enzyme papain in industry and food causes allergic sensitization].
AB  - The proteolytic enzyme papain is known to cause allergic sensitization. At a
      research laboratory several employees developed allergic symptoms after
      occupational exposure to papain dust and were referred to the local Clinic of
      Occupational Medicine. 10 out of 22 employees reported work-related ocular
      itching and symptoms of rhinitis. A Histamine Release Test showed that three
      employees were sensitized to papain. After the introduction of more stringent
      hygienic procedures including the use of a fume cupboard and external washing of
      test tubes during use, all work-related symptoms disappeared.

PMID- 18823600
TI  - [Residual limb pain from bone overgrowth after amputation].
AB  - Bone overgrowth is classified as either heterotopic or orthotopic ossification.
      Three cases are reported in which bone overgrowth caused complications in three
      adult amputees. The cases demonstrate that bone overgrowth is an important
      differential diagnosis to residual limb pain following amputation. Bone
      overgrowth after amputation is very seldom described in literature. Furthermore,
      heterotopic ossification has not previously been reported following complications
      to initial amputation but only in traumatic amputees.

PMID- 18823601
TI  - [Ulnar neuropathy in a poultry worker].
AB  - Three months after he was employed as a poultry worker, a 48-year-old man
      developed involuntary jerks of his right first, fourth, and fifth fingers,
      paraesthesiae, weakness, and eventually wasting of the first dorsal interosseous
      muscle. His job entailed repetitive lifting of boxes weighing 10-25 kg with
      flexion of the elbow, pronation of the forearm, and ulnar deviation of the wrist.
      A nerve conduction study indicated ulnar neuropathy just distal to the elbow.
      Surgery at this level alleviated the symptoms, but shortly after his return to
      work, he changed jobs because of aggravation.

PMID- 18823602
TI  - [Salmonella typhi--time to change empiric treatment].
AB  - In the present case series report we describe seven recent cases of typhoid
      fever. All the patients were travellers returning from Pakistan, where typhoid is
      endemic. Salmonella typhi isolated from the patients by blood culture were
      reported as intermediary susceptible to fluoroquinolones in six out of seven
      cases. We recommend that empiric treatment of suspected cases of typhoid fever
      includes a third generation cephalosporin such as ceftriaxon. Furthermore, the
      present report stresses the importance of typhoid vaccination of travellers to
      areas where typhoid is endemic.

PMID- 18823603
TI  - [Numbness of the chin as a paraneoplastic syndrome].
AB  - A 60-year-old woman consulted a medical specialist for numbness of the chin. A
      bilateral mental nerve affection was found. A PET-scan with fluodeoxyglucose
      revealed a localised process in the right thyroid gland. She was operated for a
      localised thyroid cancer. At follow-up, 6 years later, she was in good health
      without any symptoms apart from numbness of the chin.

PMID- 18823604
TI  - [Sentinel node technique in local relapse after breast-conserving surgery].
AB  - Mastectomy is the treatment of choice in local relapse after breast-conserving
      surgery. We present two cases where the sentinel node technique was used. The
      first case presents with one negative SN after axillary dissection 11 years
      earlier. The second case presents with a new SN with micrometastases and axillary
      dissection with 11 negative nodes 2 years after a negative SN procedure. We
      recommend the use of the sentinel node technique in surgery for relapse in order
      to optimize the staging.

PMID- 18823605
TI  - [Stress fracture in female athlete runner carrying weights].
AB  - A 32-year old female athlete was referred with a femoral neck fracture. She
      practiced intensive cycling and running while carrying weights. The fracture had
      been overlooked on multiple occasions. She suffered from underweight, Vitamin D
      deficiency, ammenorhea and osteopenia.

PMID- 18823606
TI  - [Two cases of cardial myxomas with severe course].
AB  - We describe two cases of cardial myxomas. The first had a rare location in the
      left ventricle presenting with cardiac arrest because of left ventricular outflow
      obstruction. The other myxoma has a typical localisation in the left atrium with
      symptoms of heart failure and syncope because of mitral valve occlusion. Myxomas
      are rare benign tumours with a wide spectrum of symptoms from asymptomatic to
      very serious, depending of the localisation of the tumours in relation to the
      heart valves. Eccocardiography is the examination of choice when myxoma is
      suspected. The treatment and way to final diagnostic is surgery.

PMID- 18823607
TI  - [Two cases of laryngocele].
AB  - A laryngocele is a rare benign dilatation of the anterior part of Ventriculus
      Laryngis. The symptoms are either hoarseness, a tumor on the neck or a
      combination. In the literature a link between laryngocele and carcinoma of the
      larynx is well described. For this reason a careful clinical examination together
      with MRI or CT scans is of outmost importance. None of the patients described had
      larynx cancer. Of the two patients described, one underwent surgery, the other
      was treated conservatively due to general health.

PMID- 18823608
TI  - [Severe Haemophilus influenzae b infection in healthy male adult].
AB  - Haemophilus influenzae b (Hib) can be the cause of serious infections, and is
      mainly observed affecting children and immuno-compromised patients. We report a
      case of a healthy 49-year old male with a severe Hib infection complicated by
      septicaemia, meningitis and anuria. The risk of invasive Hib infections in adults
      is reviewed.

PMID- 18823609
TI  - [Severe ileus due to hypothyroidism].
AB  - Hypothyroidism (HT) is a rare cause of ileus. A patient with ileus had several
      examinations during his hospitalization and was treated in intensive care unit
      due to septicaemia and respiratory failure. At day 25 HT was suspected. However,
      the patient was transferred between hospitals many times and blood samples were
      not seen until day 46. He suffered from severe HT and treatment had immediate
      effect on the intestinal function. This case illustrates a probable association
      between HT and ileus, and that valuable information may be lost when transferring
      severely ill patients between hospitals.

PMID- 18823610
TI  - [Autoimmune polyglandular syndrome in a 13-year old girl].
AB  - Autoimmune polyglandular syndrome (APS) is an entity, defined by autoimmunity
      towards two or more endocrine organs. APS is classified in 3 subgroups (type-1,
      type-2a, type-2b), according to the organs involved. A case is presented of a 13
      year old girl referred to the Department of Paediatrics with hypothyroidism,
      subsequently diagnosed adrenocortical insufficiency and impending Addison crisis,
      typical for APS-type 2a. In the paper we discuss the need for more attention to
      APS in clinical work.

PMID- 18823611
TI  - [Congenital radioulnar synostosis].
AB  - Congenital radio-ulnar synostosis is a rare condition with approximately 350
      cases reported in the literature. The condition is due to the failure of
      segmentation between the radius and ulna. The rarity of the condition often leads
      to delayed clinical diagnosis. Average age at diagnosis is 6 years, and ranges
      from 6 months to 22 years. The sexes are affected 3-2 male/female and 60% of
      cases are bilateral. Functional deficits with congenital radio-ulnar synostosis
      depend on the severity of the deformity and on whether or not it is bilateral.
      The disability is most significant in bilateral cases with severe pronation.
      Children initially may have reduced radial heads and later develop symptomatic
      radial head subluxation as adolescents. Therefore, they must be followed-up
      radiographically. Indications for surgery still remain somewhat controversial but
      are related to bilaterality and the degree of deformity.

PMID- 18823612
TI  - [Rapid growing liposarcoma in retroperitoneum].
AB  - A 36-year-old male was admitted with a giant abdominal tumour and dyspnoea from
      thoracic displacement. Symptoms were one year of haemorrhoids, but complaints of
      growing abdomen presented only for 10 weeks. Ultrasound could not differentiate
      tumour from the liver, but MR scan could. A 24.2 kg inhomogeneous tumour adhesive
      to the right kidney capsule was removed in toto from retroperitoneum.
      Histological diagnosis: Sclerosing, low differentiated liposarcoma. Besides
      radical surgery only radiation therapy may have effect in treatment of
      retroperitoneal soft tissue sarcomas.

PMID- 18823613
TI  - [Severe metabolic acidosis in an alcoholic].
AB  - Severe metabolic acidosis is associated with poor prognosis. We present a patient
      with profound alcohol and starvation-related combined lactic and keto acidosis
      (lactate = 29 mM; pH = 6.83) who made a good recovery following 18 hours of
      intensive care therapy. A brief summary of the proposed mechanism by which these
      metabolic derangements develop is presented.

PMID- 18823614
TI  - [Diagnosis of meningococcal sepsis by real-time polymerase chain reaction].
AB  - Approximately 100 cases of meningococcal disease are reported annually in
      Denmark; 90% of these cases are confirmed by culture and serological methods.
      Real-time PCR was introduced in Denmark in 2005 as a diagnostic tool for
      meningococcal disease. We hereby report the first notified case of meningococcal
      sepsis in Denmark where real-time PCR was the primary positive microbiological
      result.

PMID- 18823615
TI  - Thoracoabdominal incision: a forgotten tool in the management of complex upper
      gastrointestinal complications.
AB  - BACKGROUND: The gastroesophageal junction was commonly approached surgically
      through a thoracoabdominal incision. With the advent of improved retraction
      devices, this has been abandoned because the upper midline incision has provided
      adequate exposure with decreased morbidity. However, exposure of the
      gastroesophageal junction remains a challenge in the setting of surgical
      complications associated with repeat surgeries and abscess formation. METHODS:
      Patients were placed in the right lateral decubitus position. An incision was
      made 2 cm below the tip of the scapula to a point in the midline equidistant from
      the xiphoid process to the umbilicus. The chest was entered at the eighth
      intercostal space. The abdominal cavity was entered by dividing the diaphragm
      peripherally from its lateral attachments to the ribs. RESULTS: We have used this
      approach on 4 patients. All patients were discharged home tolerating oral diets.
      The average postoperative stay was 10 days. No complications related to the
      incision were reported. At the 6-month follow-up evaluation all patients
      continued to tolerate a regular diet without difficulties. CONCLUSIONS: The
      technique described allows for excellent exposure of the upper gastrointestinal
      tract in a subset of patients with complex upper gastrointestinal complications.

PMID- 18823616
TI  - Comparison of outcomes of arteriovenous grafts and fistulas at a single Veterans'
      Affairs medical center.
AB  - BACKGROUND: Before 2003, almost all dialysis access procedures performed at the
      G.V. Montgomery Veterans' Affairs Medical Center were arteriovenous grafts. In
      mid-2003, it was decided to place fistulas in most patients. This study compared
      the patency rates and frequency of interventions to maintain function between the
      2 procedures. METHODS: Patency rates for 64 grafts and 50 fistulas were computed
      using Kaplan-Meier life-tables and compared using the Cox-Mantel log- rank test.
      The frequency of interventions to maintain function was compared using a Poisson
      model. RESULTS: Primary patency of grafts at 1 and 2 years was 39% and 26%, and
      that of fistulas was 44% and 37%. Secondary patency of grafts at 1 and 2 years
      was 71% and 63%, and that of fistulas was 75% and 72%. Neither difference reached
      significance. The difference in interventions also was insignificant.
      CONCLUSIONS: Switching from grafts to fistulas did not significantly improve the
      patency and frequency of interventions.

PMID- 18823617
TI  - Management of patients with concomitant lung cancer and abdominal aortic
      aneurysm.
AB  - BACKGROUND: Management of patients with an abdominal aortic aneurysm (AAA) and
      malignancy is challenging. We aimed to define the coincidence of AAA and lung
      cancer and to determine a treatment strategy. METHODS: The outcomes for patients
      diagnosed with AAA and lung cancer between 1991 and 2004 at our institution were
      reviewed retrospectively. RESULTS: We identified 75 patients with both lesions
      among 1,096 AAA and 1,875 lung cancer patients. Survival correlated with cancer
      stage; only 3 deaths were directly attributable to the patient's AAA. Of 59
      patients who did not have AAA repair at the time of cancer diagnosis, 12 were
      repaired. Twenty-seven of those 59 patients had a 5.0-cm or larger AAA; only 1
      patient with a 7.5-cm AAA had a rupture 5 months after thoracotomy and died.
      CONCLUSIONS: The co-existence of AAA and lung cancer is not rare; prognosis is
      poor and largely determined by the lung cancer stage. Open or endovascular repair
      of AAA rarely is justified in patients with advanced disease unless the AAA is
      symptomatic or large (>7 cm). Treatment for AAAs greater than 5.5 cm should be
      based on stage, histology, and patient comorbidities.

PMID- 18823618
TI  - Surgical outcomes and survival after multiorgan resection for locally advanced
      gastric cancer.
AB  - BACKGROUND: Multiple organ resection for locally advanced (assumed T4) gastric
      cancer is associated with high morbidity and mortality. Our aim was to evaluate
      the efficacy of these surgeries with regard to surgical morbidity, mortality, and
      survival. METHODS: Fifty-six patients underwent potentially radical gastrectomy
      combined with invaded organ resection. Early and late results of multiorgan
      resection and clinicopathologic factors influencing these results were evaluated.
      RESULTS: Forty patients (71.4%) received 1 additional organ resection and 16
      patients (28.6%) received 2 or more additional organ resections. Postoperative
      morbidity and mortality was 37.5% and 12.5%, respectively. Resection of 2 or more
      additional organs increased postoperative morbidity and advanced age increased
      mortality. The 1- and 3-year survival rates were 53.3% and 28.1%, respectively.
      Advanced age, lymph node metastasis, and resection of more than 1 additional
      organ were significant prognostic factors for survival. CONCLUSIONS: For patients
      with locally advanced gastric carcinoma, multiple organ resection is worthwhile
      with careful patient selection.

PMID- 18823619
TI  - Trityl-derivatized carbohydrates immobilized on a polystyrene microplate.
AB  - Carbohydrate biosensors, including carbohydrate arrays, are attracting increased
      attention for the comprehensive and high-throughput investigation of protein
      carbohydrate interactions. Here, we describe an effective approach to fabricating
      a robust microplate-based carbohydrate array capable of probing protein binding
      and screening for inhibitors in a high-throughout manner. This approach involves
      the derivatization of carbohydrates with a trityl group through an alkyl linker
      and the immobilization of the trityl-derivatized carbohydrates (mannose and
      maltose) onto microplates noncovalently to construct carbohydrate arrays. The
      trityl carbohydrate derivative has very good immobilization efficiency for
      polystyrene microplates and strong resistance to aqueous washing. The
      carbohydrate arrays can probe the interactions with the lectin Concanavalin A and
      screen this protein for the well-known inhibitors methyl alpha-D-mannopyranoside
      and methyl alpha-D-glucopyranoside in a high-throughput manner. The method
      described in this paper represents a convenient way of fabricating robust
      noncovalent carbohydrate arrays on microplates and offers a convenient platform
      for high-throughput drug screening.

PMID- 18823620
TI  - Preferential recognition of peroxynitrite modified human DNA by circulating
      autoantibodies in cancer patients.
AB  - Peroxynitrite (ONOO(-)) has been vastly implicated in mutagenesis and cancer
      development. Present study probes the antigenicity of peroxynitrite damaged DNA
      (ONOO(-)-DNA) in cancer patients. Purified human placental DNA was damaged by the
      synergistic action of sodium nitroprusside (SNP) and Pyrogallol for 3h at 37
      degrees C. Binding characteristics of cancer autoantibodies as well as
      experimentally induced anti-peroxynitrite-DNA (anti-ONOO(-)-DNA) antibodies were
      assessed by ELISA and band shift assay. DNA modifications produced single strand
      breaks, decreased melting temperature (T(m)), hyperchromicity in UV spectrum and
      decreased fluorescence intensity. The ONOO(-)-DNA induced high titre antibodies
      in experimental animals. Cancer autoantibodies exhibited enhanced binding with
      the modified DNA as compared to the native form. Lymphocyte DNA from cancer
      patients showed appreciable recognition of anti-ONOO(-)-DNA IgG as compared to
      the DNA from healthy subjects. The peroxynitrite modified DNA presents unique
      epitopes which may be one of the factors for the autoantibody induction in cancer
      patients.

PMID- 18823621
TI  - Mathematical approach to understand the kinetics of alpha-synuclein aggregation:
      relevance to Parkinson's disease.
AB  - alpha-Synuclein aggregation is a hallmark pathological feature in Parkinson's
      disease (PD). The conversion of alpha-synuclein from soluble monomer to insoluble
      aggregates through the toxic oligomeric intermediates underlie the
      neurodegeneration associated with PD. Redox active metal ions such as iron (Fe)
      and copper (Cu) are known to enhance alpha-synuclein fibrillogenesis. In the
      present study, we have implemented mathematical approach to monitor the kinetics
      of aggregation of alpha-synuclein nucleation and elongation constants based on
      fluorescence studies. In this pretext, we have implemented mathematical
      simulations like self and absolute analysis. The mathematical model discussed in
      this paper is the first of its kind and might prove useful for predicting the
      drug intervention time to prevent alpha-synuclein aggregation and has future
      clinical application.

PMID- 18823622
TI  - A quantitative method for representing balance strategies of goal-directed human
      motions.
AB  - A movement index termed balance strategy vector (BSV) was developed as a research
      tool for studying human balance strategies during goal-directed motions. For a
      given motion (motion capture data), the BSV index quantitatively represents its
      balance strategy by computing how available body joint DoFs' angular motions
      affect the formation of the wholebody center-of-mass trajectory. The index
      facilitates easy and intuitive understanding of balance strategies of various
      human motions and can assist scientific investigations on human balance
      strategies. As an example demonstrating the utility of the index, the index was
      used to explore balance strategies of free-style, sagittal-plane load lifting
      motions.

PMID- 18823623
TI  - Computer simulation of topical knee cooling.
AB  - Local topical cooling with gel-packs or cryo-cuffs is often used after surgery or
      after knee injuries. Mostly beneficial, but some deleterious effects have been
      reported in literature. The spatial distribution of heat/cold through different
      tissues of the knee in time may be responsible for different effects of cooling
      on the traumatized or inflamed tissue and have yet to be studied. Parallel
      computer simulation was used to study, non-invasively, temperature changes in the
      knee during cooling. A 3-D computer model of the knee, with a spatial resolution
      of 1mm, was derived from cross sections available in the visible human dataset.
      Heat transfer in a non-homogenous knee tissue was modeled with a diffusion
      equation, which was solved by the explicit finite difference method. The heat
      transfer between blood and tissue and tissue metabolism have also been modeled
      and simulated. Two different simulations were performed: cooling with a liquid at
      constant temperature (cryo-cuff) and topical cooling with frozen gel-packs. The
      simulated results were analyzed and compared with relevant measurements.

PMID- 18823624
TI  - Analysis of the helical plate for bone fracture fixation.
AB  - The improvements in oblique fracture fixation by means of the hemi-helical plate
      (HHP) to provide the bone-plate-screw assembly with enhanced holding capacity are
      discussed. The HHP is designed to provide stable fixation for helical cracks
      caused by torsional loading, such that the bone interfaces at the crack are
      brought into apposition and compressive strains are applied at the cracked
      interfaces. The HHP wraps around the bone, and hence is also suited for fixation
      of comminuted fractures. This is because, instead of employing multiple screws
      across the cracks, the HHP holds the bone fragments together. First, we
      illustrate through experiments the special capabilities of the HHP with respect
      to its fracture-holding capability, in comparison with straight-plate fixation
      with different screw orientations (convergent, divergent, alternately convergent
      and divergent, and perpendicular). Second, the finite-element (FE) analysis of
      the HHP is described, to elucidate the efficacy of fracture-gap movement and
      closure, and the flexibility of the fixation under compressive, bending moment
      and torsional loads.

PMID- 18823625
TI  - Predicting nurse burnout from demands and resources in three acute care hospitals
      under different forms of ownership: a cross-sectional questionnaire survey.
AB  - BACKGROUND: Health care organizations have changed dramatically over the last
      decades, with hospitals undergoing restructurings and privatizations. OBJECTIVES:
      The aim of this study is to enhance the understanding of the origin and
      prevalence of burnout in health care by investigating factors in the psychosocial
      work environment and comparing three Swedish emergency hospitals with different
      types of ownership. DESIGN: A cross-sectional design was used. PARTICIPANTS: We
      selected a total sample of 1800 registered nurses from three acute care
      hospitals, one private for-profit, one private non-profit and one publicly
      administered. A total of 1102 questionnaires were included in the analyses.
      SETTINGS: The examined ownership types were a private for-profit, a private non
      profit and a traditional publicly administered hospital. All were situated in the
      Stockholm region, Sweden. METHODS: Data were collected by questionnaires using
      validated instruments, in accordance with the Job Demands-Resources Model and
      Maslach's Burnout Inventory. Descriptive statistics, correlation analyses,
      multivariate covariance analyses and multiple regression analyses were conducted.
      RESULTS: The results showed that the burnout levels were the highest at the
      private for-profit hospital and lowest at the publicly administered hospital.
      However, in contrast to expectations the demands were not higher overall at the
      for-profit organization or lowest at the public administration unit, and overall,
      resources were not better in the private for-profit or worse at the publicly
      administered hospital. Multiple regression analyses showed that several of the
      demands included were related to higher burnout levels. Job resources were linked
      to lower burnout levels, but not for all variables. CONCLUSIONS: Profit
      orientation in health care seems to result in higher burnout levels for
      registered nurses compared to a publicly administered hospital. In general,
      demands were more predictive of burnout than resources, and there were only
      marginal differences in the pattern of predictors across hospitals.

PMID- 18823626
TI  - Impact factors and citations counts: a state of disquiet.

PMID- 18823627
TI  - Association of lipoprotein lipase D9N polymorphism with myocardial infarction in
      type 2 diabetes: the genetics, outcomes, and lipids in type 2 diabetes (GOLD)
      study.
AB  - The association of polymorphisms affecting lipid metabolism with the risk of
      myocardial infarction (MI) in type 2 diabetes mellitus was investigated. The
      Genetics, Outcomes and Lipids in type 2 Diabetes (GOLD) Study is a prospective,
      multicenter study, conducted on 990 patients presenting diabetes and MI (n=386),
      or diabetes without previous manifestation of stroke, peripheral or coronary
      arterial disease (n=604), recruited from 27 institutions in Brazil. APO A1 (A/G 
      75 and C/T +83) and APO C3 (C/G 3'UTR) non-coding sequences, CETP (Taq 1B), LPL
      (D9N), APO E (epsilon2, epsilon3, epsilon4,), PON-1 (Q192R), and two LCAT
      variants Arg(147)-->Trp and Tyr(171)-->Stop were tested by PCR-RFLP. There was a
      higher prevalence of LPL DN genotype (19% vs.12%, p=0.03) and a higher frequency
      of the N allele (11% vs. 7%) among subjects with MI when compared to controls,
      with an odds ratio of MI for carriers of 9N allele of 2.46 (95% CI=1.79-3.39,
      p<0.0001). This association was present in men and women, in non-smokers and in
      hypertensive patients. A logistic regression model including gender, duration of
      diabetes, systolic blood pressure, HDL-C, left ventricle hypertrophy and D9N
      polymorphism showed that the latter still remained significantly associated with
      MI (OR=1.50, 95% CI=1.02-2.25, p=0.049). These findings suggest that D9N
      polymorphism can be a useful risk marker for myocardial infarction and that
      further potential candidate genes should be screened for exploratory analysis and
      for future therapeutic intervention in diabetes.

PMID- 18823628
TI  - Physiologic deformational loading does not counteract the catabolic effects of
      interleukin-1 in long-term culture of chondrocyte-seeded agarose constructs.
AB  - An interplay of mechanical and chemical factors is integral to cartilage
      maintenance and/or degeneration. Interleukin-1 (IL-1) is a pro-inflammatory
      cytokine that is present at elevated concentrations in osteoarthritic joints and
      initiates the rapid degradation of cartilage when cultured in vitro. Several
      short-term studies have suggested that applied dynamic deformational loading may
      have a protective effect against the catabolic actions of IL-1. In the current
      study, we examine whether the long-term (42 days) application of dynamic
      deformational loading on chondrocyte-seeded agarose constructs can mitigate these
      catabolic effects. Three studies were carried out using two IL-1 isoforms (IL
      1alpha and IL-1beta) in chemically defined medium supplemented with a broad range
      of cytokine concentrations and durations. Physiologic loading was unable to
      counteract the long-term catabolic effects of IL-1 under any of the conditions
      tested, and in some cases led to further degeneration over unloaded controls.

PMID- 18823629
TI  - Ionic liquid supported three-phase liquid-liquid-liquid microextraction as a
      sample preparation technique for aliphatic and aromatic hydrocarbons prior to gas
      chromatography-mass spectrometry.
AB  - For the first time hollow fiber-protected ionic liquid supported three-phase
      (liquid-liquid-liquid) microextraction (HFM-LLLME) was developed for the gas
      chromatography-mass spectrometric (GC-MS) analysis of aromatic and aliphatic
      hydrocarbons. The hydrocarbons were extracted from 10 ml of aqueous samples
      though small volumes of ionic liquid and organic solvent in the hollow fiber
      membrane HFM) wall and channel, respectively. The ionic liquid was immiscible
      with both the aqueous sample and the organic solvent (toluene). After extraction,
      the enriched solvent was directly injected into a GC-MS system for analysis
      without any further pretreatment. Ionic liquid supported HFM-LLLME shows better
      extraction performance than two-phase HFM-liquid-phase microextraction, in which
      only organic solvent is involved, and solid-phase microextraction. The ionic
      liquid and organic solvent combination found most suitable for HFM-LLLME was 1
      butyl-3-methylimidazolium hexafluorophosphate, and toluene, respectively. This
      new technique provided up to 210-fold enrichment of aliphatic and aromatic
      hydrocarbons in 40 min with good reproducibility (<11%) and limits of detection
      (1-7 ng l(-1)).

PMID- 18823630
TI  - Evaluation of various immobilized enzymatic microreactors coupled on-line with
      liquid chromatography and mass spectrometry detection for quantitative analysis
      of cytochrome c.
AB  - An in-line procedure for protein analysis using a trypsin-based immobilized
      enzymatic reactor (IMER) coupled to LC-MS/MS has been developed. Various IMERs
      were synthesized and characterized by estimating the digestion yield of a pattern
      peptide in UV detection. Laboratory-made IMERs were optimized by studying the
      effect of different parameters as the nature of the functionalized immobilization
      support (silica, agarose), the amount of immobilized trypsin and the binding
      density. The potential of the laboratory-made IMERs were compared with a batch
      digestion and with a commercial trypsin-based IMER. The laboratory-made IMER
      based on CNBr-activated Sepharose showed the best performances in terms of
      digestion yields, digestion time, price and repeatability (RSD<4%). Cytochrome c
      was then digested on this IMER and used in-line with LC-MS. The target protein
      was easily recognized by the Mascot database until 17pmol injected.

PMID- 18823631
TI  - The free solution electrophoretic mobility of peptides by a bead modeling
      methodology.
AB  - A bead modeling methodology, BMM, discussed previously to compute the free
      solution electrophoretic mobility of peptides [H. Pei, Y. Xin, S.A. Allison, J.
      Sep. Sci. 31 (2008) 554-564], is generalized to avoid the approximation of
      orientationally preaveraging hydrodynamic interaction. In general, peptide
      mobilities computed without preaveraging are lower by about 2%. The BMM is then
      used to study the free solution electrophoretic mobility of several insect
      oostatic peptides reported previously in a variety of different buffer systems
      ranging in pH from 2.25 to 8.1 [V. Solinova, V. Kasicka, D. Koval, J. Hlavacek,
      Electrophoresis, 25 (2004) 2299-2308]. With minor adjustment of the intrinsic
      pK(a0) of the N-terminal peptide, good agreement between modeling and experiment
      is achieved for peptide models with random secondary structures in the entire pH
      range. Model mobilities of these peptides appear to be relatively insensitive to
      the assumed secondary structure.

PMID- 18823632
TI  - Comparison between charged aerosol detection and light scattering detection for
      the analysis of Leishmania membrane phospholipids.
AB  - The performance of charged aerosol detection (CAD) was compared to evaporative
      light scattering detection (ELSD) for the analysis of Leishmania membrane
      phospholipid (PL) classes by NP-HPLC. In both methods, a PVA-Sil column was used
      for the determination of the major Leishmania membrane PLs, phosphatidic acid,
      phosphatidylglycerol, cardiolipin, phosphatidylinositol,
      phosphatidylethathanolamine, phosphatidylserine, lysophosphatidylethathanolamine,
      phosphatidylcholine, sphingomyelin and lysophosphatidylcholine in the same
      analysis. Although the response of both detection methods can be fitted to a
      power function, CAD response can also be described by a linear model with
      determination coefficients (R(2)) ranging from 0.993 to 0.998 for an injected
      mass of 30 ng to 20.00 microg. CAD appeared to be directly proportional when a
      restricted range was used and it was found to be more sensitive at lowest mass
      range than ELSD. With HPLC-ELSD the limits of detection (LODs) were between 71
      and 1195 ng and the limits of quantification (LOQs) were between 215 and 3622 ng.
      With HPLC-CAD, the LODs were between 15 and 249 ng whereas the limits of
      quantification (LOQs) were between 45 and 707 ng. The accuracy of the methods
      ranged from 62.8 to 115.8% and from 58.4 to 110.5% for ELSD and CAD,
      respectively. The HPLC-CAD method is suitable to assess the influence of
      miltefosine on the composition of Leishmania membrane phospholipids.

PMID- 18823633
TI  - Pulsed flow modulation two-dimensional comprehensive gas chromatography-tandem
      mass spectrometry with supersonic molecular beams.
AB  - Pulsed flow modulation (PFM) two-dimensional comprehensive gas chromatography (GC
      x GC) was combined with quadrupole-based mass spectrometry (MS) via a supersonic
      molecular beam (SMB) interface using a triple-quadrupole system as the base
      platform, which enabled tandem mass spectrometry (MS-MS). PFM is a simple GC x GC
      modulator that does not consume cryogenic gases while providing tunable second GC
      x GC column injection time for enabling the use of quadrupole-based mass
      spectrometry regardless its limited scanning speed. The 20-ml/min second column
      flow rate involved with PFM is handled, splitless, by the SMB interface without
      affecting the sensitivity. The combinations of PFM GC x GC-MS with SMB and PFM GC
      x GC-MS-MS with SMB were explored with the analysis of diazinon and permethrin in
      coriander. PFM GC x GC-MS with SMB is characterized by enhanced molecular ion and
      tailing-free fast ion source response time. It enables universal pesticide
      analysis with full scan and data analysis with reconstructed single ion
      monitoring on the enhanced molecular ion and another prominent high mass fragment
      ion. The elimination of the third fragment ion used in standard three ions method
      results in significantly reduced matrix interference. GC x GC-MS with SMB
      improves the GC separation, and thereby our ability for sample identification
      using libraries. GC-MS-MS with SMB provides better reduction (elimination) of
      matrix interference than GC x GC-MS. However, it is a target method, which is not
      always applicable. GC x GC-MS-MS does not seem to further reduce matrix
      interferences over GC-MS-MS and unlike GC x GC-MS, it is incompatible with
      library identification, but it is beneficial to have both GC x GC and MS-MS
      capabilities in the same system.

PMID- 18823634
TI  - Histopathological distinction and evaluation of biliary and peribiliary cysts in
      pig liver.
AB  - The majority of hepatic cysts identified in animals are considered to derive from
      the intrahepatic bile ducts (biliary cysts). An alternative origin is the
      peribiliary glands located in the hilum of the liver and large portal tracts
      (peribiliary cysts). The distinction between biliary and peribiliary cysts, and
      whether these have different clinical significance, has rarely been considered
      previously. This study reports the pathological features of five cystic porcine
      livers. Four of these five livers had both biliary and peribiliary cysts and the
      fifth had only biliary cysts. Biliary cysts were not associated with distortion
      of adjacent hepatic parenchyma, whereas peribiliary cysts appeared to cause local
      compression and circulatory disturbance. It would therefore appear that
      peribiliary cysts have greater potential clinical significance than those of
      biliary origin.

PMID- 18823635
TI  - Localization of fibropapilloma-associated turtle herpesvirus in green turtles
      (Chelonia mydas) by in-situ hybridization.
AB  - Fibropapilloma-associated turtle herpesvirus (FPTHV) is the presumed aetiological
      agent of sea turtle fibropapillomatosis (FP). Intralesional DNA and RNA of the
      virus have been detected by polymerase chain reaction (PCR) and reverse
      transcriptase-PCR (RT-PCR), respectively, but the exact location and distribution
      of the virus within the tumours have not been addressed. In this study, in-situ
      hybridization (ISH) was used to investigate viral transcriptional activity and
      localization of FPTHV. Twenty-five tumours were obtained from the skin or
      conjunctiva of 105 green turtles (Chelonia mydas) examined on two islands in
      Puerto Rico (Culebra and Culebrita). These lesions comprised 19 fibropapillomas
      and six fibromas. FPTHV mRNA transcripts were detected by ISH in three
      fibropapillomas, with positive reactions confined to the nuclei of clusters of
      epithelial cells. Viral DNA was detected by riboprobe ISH combined with
      denaturation in 14 tumours, including both fibropapillomas and fibromas. Signals
      were confined to the nuclei of acanthotic epithelial cells and were not seen in
      the subepithelial fibrous areas of the tumours. These results suggest that FPTHV
      is present in epithelial cells and transcriptionally active in fibropapillomas.

PMID- 18823636
TI  - Gastric lesions and immune responses caused by long-term infection with
      Helicobacter heilmannii in C57BL/6 mice.
AB  - Helicobacter heilmannii is a gastric micro-organism that can induce gastritis and
      B-cell MALT (mucosa-associated lymphoid tissue) lymphoma in mice, in a host
      dependent manner. The present study was designed to examine gastric lesions and
      immune responses caused by intragastric H. heilmannii infection of an inbred
      mouse strain, C57BL/6. Long-term infection led to the formation of gastric
      nodules and increased mucosal thickness of the stomach, due to gastric epithelial
      proliferation. Infection also induced the formation of lymphoid follicles in the
      corpus mucosa and submucosa. The follicular cells were mainly CD45R+ cells that
      did not produce immunoglobulin. However, scattered in the lamina propria and
      corpus submucosa, numerous IgA+ cells were found in infected mice, but not in
      control mice. RT-PCR results showed that H. heilmannii infection led to increased
      mRNA expression for IFN-gamma (a Th1 cytokine) and IL-10 (a Th2 cytokine) in the
      mouse stomach, suggesting that both Th1 and Th2 responses are associated with H.
      heilmannii infection. The mRNA of other cytokines and chemokines (IL-1beta, IL
      12p40, TNF-alpha, MCP-1, KC and MIP-2) was also increased by infection.

PMID- 18823637
TI  - Development and validation of a predictive outcome score of cerebral venous
      thrombosis.
AB  - BACKGROUND AND PURPOSE: Cerebral venous thrombosis (CVT) is a rare disease with a
      variable outcome. The aim of this study was to develop and validate a predictive
      outcome score for CVT patients. METHODS: The score was based on the 8 predictive
      variables of poor outcome (modified Rankin Scale score>2) from the International
      Study on Cerebral Vein and Dural Sinus Thrombosis: age >37, male, mental status
      disorder, coma, intracranial hemorrhage, deep CVT, CNS infection, and malignancy.
      To assign a weighted index (WI), the natural logarithm of the hazard ratio of
      each variable was calculated, multiplied by 10 and rounded to the nearest
      integer. The individual score of each patient was the sum of the WI. The
      validation sample consisted of a retrospective single center cohort of 90 CVT
      patients. RESULTS: Sixteen patients (18%) had a poor outcome. The predictive
      score had an area under the receiver operating characteristic curve of 0.81 (95%
      CI 0.71-0.90). The cut-off score with the maximum sum of sensitivity and
      specificity was a score> or =14 with sensitivity of 88% (81%-95%) and specificity
      of 70% (61%-79%). The predictive value of a score<14 for good outcome was 96%
      (92%-100%), whereas the predictive value of a score> or =14 for poor outcome was
      39% (29%-49%). CONCLUSIONS: This relatively simple predictive outcome score may
      be useful in CVT patients. A cut-off score of 14 reliably predicts good outcome,
      but is less accurate in predicting poor outcome.

PMID- 18823638
TI  - Empirical models to identify mechanisms driving reductions in tissue mercury
      concentration during culture of farmed southern bluefin tuna Thunnus maccoyii.
AB  - Two empirical models are presented to elucidate the mechanisms driving reductions
      in the mercury concentration of southern bluefin tuna (SBT) during culture. Model
      1 predicts temporal fluctuations in mercury concentration in response to growth
      dilution. Model 2 predicts the combined effects of growth dilution and linear
      mercury accumulation. Model 2 was found to be the more accurate model. Over a
      typical farming period of 136 days, growth dilution resulted in a reduction in
      mean mercury concentration of SBT edible tissues from 0.51 mg/kg down to 0.33
      mg/kg. Extended culture beyond 136 days resulted in an increase in mercury
      concentration due to the combined effects of mercury accumulation and seasonal
      lipid depletion. Results indicate that under current industry practice, cultured
      SBT can be consumed twice as frequently as that of wild caught SBT while
      maintaining total dietary mercury intake below national recommendations.

PMID- 18823639
TI  - Intermittent preventive treatment for malaria and anaemia control in Tanzanian
      infants; the development and implementation of a public health strategy.
AB  - Minimizing the time between efficacy studies and public health action is
      important to maximize health gains. We report the rationale, development and
      implementation of a district-based strategy for the implementation of
      intermittent preventive treatment in infants (IPTi) for malaria and anaemia
      control in Tanzania. From the outset, a research team worked with staff from all
      levels of the health system to develop a public-health strategy that could
      continue to function once the research team withdrew. The IPTi strategy was then
      implemented by routine health services to ensure that IPTi behaviour-change
      communication materials were available in health facilities, that health workers
      were trained to administer and to document doses of IPTi, that the necessary
      drugs were available in facilities and that systems were in place for stock
      management and supervision. The strategy was integrated into existing systems as
      far as possible and well accepted by health staff. Time-and-motion studies
      documented that IPTi implementation took a median of 12.4 min (range 1.6-28.9)
      per nurse per vaccination clinic. The collaborative approach between researchers
      and health staff effectively translated research findings into a strategy fit for
      public health implementation.

PMID- 18823640
TI  - Identification of genetic determinants of a tick-borne flavivirus associated with
      host-specific adaptation and pathogenicity.
AB  - Tick-borne flaviviruses are maintained in nature in an enzootic cycle involving a
      tick vector and a vertebrate host. Thus, the virus replicates in two disparate
      hosts, each providing selective pressures that can influence virus replication
      and pathogenicity. To identify viral determinants associated with replication in
      the individual hosts, plaque purified Langat virus (TP21pp) was adapted to growth
      in mouse or tick cell lines to generate two virus variants, MNBp20 and ISEp20,
      respectively. Virus adaptation to mouse cells resulted in four amino acid changes
      in MNBp20 relative to TP21pp, occurring in E, NS4A and NS4B. A comparison between
      TP21pp and ISEp20 revealed three amino acid modifications in M, NS3 and NS4A of
      ISEp20. ISEp20, but not MNBp20, was attenuated following intraperitoneal
      inoculation of mice. Following isolation from mice brains, additional mutations
      reproducibly emerged in E and NS3 of ISEp20 that were possibly compensatory for
      the initial adaptation to tick cells. Thus, our data implicate a role for E, M,
      NS3, NS4A and NS4B in host adaptation and pathogenicity of tick-borne
      flaviviruses.

PMID- 18823641
TI  - Removal of ammonia from contaminated air in a biotrickling filter - denitrifying
      bioreactor combination system.
AB  - The removal of gaseous ammonia in a system consisting of a biotrickling filter, a
      denitrification reactor and a polishing bioreactor for the trickling liquid was
      investigated. The system allowed sustained treatment of ammonia while preventing
      biological inhibition by accumulating nitrate and nitrite and avoiding generation
      of contaminated water. All bioreactors were packed with cattle bone composite
      ceramics, a porous support with a large interfacial area. Excellent removal of
      ammonia gas was obtained. The critical loading ranged from 60 to 120 gm(-3)h(-1)
      depending on the conditions, and loadings below 56 gm(-3)h(-1) resulted in
      essentially complete removal of ammonia. In addition, concentrations of ammonia,
      nitrite, nitrate and COD in the recycle liquid of the inlet and outlet of each
      reactor were measured to determine the fate of nitrogen in the reactor, close
      nitrogen balances and calculate nitrogen to COD ratios. Ammonia absorption and
      nitrification occurred in the biotrickling filter; nitrate and nitrite were
      biologically removed in the denitrification reactor and excess dissolved COD and
      ammonia were treated in the polishing bioreactor. Overall, ammonia gas was very
      successfully removed in the bioreactor system and steady state operation with
      respect to nitrogen species was achieved.

PMID- 18823642
TI  - Amendment of hydroxyapatite in reduction of tetrachloroethylene by zero-valent
      zinc: its rate enhancing effect and removal of Zn(II).
AB  - The effects of hydroxyapatite (HAP) on dechlorination of tetrachloroethylene
      (PCE) by zero-valent zinc (ZVZ) were examined in batch systems. PCE was primarily
      transformed to trichloroethylene by ZVZ, with 1,2-trans-dichloroethylene
      representing a minor product. Dechlorination of PCE was accelerated by the
      presence of HAP, and the pseudo-first order rate constants increased with
      increasing amount of HAP. Zn(II), mostly generated from oxidative dissolution of
      ZVZ by PCE, was effectively removed from the solution by HAP. Ion substitution,
      coprecipitation, and adsorption are proposed as the possible mechanisms for
      Zn(II) removal. These reactions appeared to occur simultaneously and the
      contribution of each reaction to overall removal of Zn(II) was primarily
      dependent on HAP loading at constant ZVZ loading. The results indicate that the
      use of HAP in combination with conventional zero-valent metals is promising in
      that it can achieve both degradation of organic contaminants and stabilization of
      inorganic contaminants.

PMID- 18823643
TI  - Effects of human activities and urbanization on groundwater environments: an
      example from the aquifer system of Tokyo and the surrounding area.
AB  - The Kanto plain that is the largest depositional plain in Japan has the largest
      urbanized area called Tokyo Metropolitan Area. This plain has experienced
      extensive groundwater withdrawals for water resources and human induced disasters
      such as land subsidence in the process of urbanization. Japanese national
      government and local governments have monitored groundwater levels and settlement
      of ground surface for about half a century. These data are useful not only for
      the prevention of these disasters but for the evaluation of the change of
      groundwater flow beneath the urbanized area. However, few hydrological and
      hydrogeological studies about the change of groundwater flow in this plain have
      been conducted until now except for several studies which were limited in areal
      extent. In this paper, changes of the distribution of hydraulic heads in the
      central part of this plain are discussed using the long-term groundwater level
      observation data to evaluate the change of groundwater flow. The temporal changes
      in the distribution of hydraulic heads in a major confined aquifer (the second
      aquifer) and the areal extent of the urbanized area for approximately 50 years
      can be summarized as follows. In the latter half of the 1950s, urban area was
      limited in the southern region of the study area and hydraulic head gradually
      declined from the northwest to the southeast in the study area. After the 1960s,
      urban area extended toward the north and groundwater in the northern part was
      largely abstracted until the 1980s. As a result, hydraulic heads in this area
      markedly declined. On the other hand, hydraulic heads in the southern part began
      to rise because of the restriction of groundwater withdrawals. In recent years,
      low hydraulic head area has been formed from the northern region to the central
      region. These results suggest that the groundwater flow which was affected by
      urbanization (groundwater withdrawals) has continued to change over several
      decades, even after the regulation of withdrawals, and hence, the continued
      monitoring of the groundwater environment is important for the sustainable use of
      groundwater resources.

PMID- 18823644
TI  - Methane oxidation in a boreal climate in an experimental landfill cover composed
      from mechanically-biologically treated waste.
AB  - The present study evaluated microbial methane (CH4) oxidation in a boreally
      located outdoor landfill lysimeter (volume 112 m3, height 3.9 m) filled with
      mechanically-biologically treated waste (MBT residual) and containing a cover
      layer made from the same MBT residual. The calculations based on gas emission and
      pore gas measurements showed that, between April and October 2005, a significant
      proportion (> 96%) of the methane produced (< 23 l CH4 m(-2) d(-1)) in the
      lysimeter was oxidized. Methane was oxidized mainly at the depths of 35-75 cm, as
      indicated by the upward decrease both in the methane concentration and in the
      methane-to-carbon dioxide ratio in the pore gas. Lower methane oxidation (< 0.8
      CH4 m(-2) d(-1); this was < 22% of the methane produced) was observed only during
      the coldest time of the year (January 2006), apparently due to the fall in
      temperature at the depths of 25-70 cm (from 9-25 degrees C during April to
      October to 2-9 degrees C in January). Unexpectedly, the highest methane oxidation
      potential (MOP) was observed in samples from the top layer where exposure to
      methane was low. Overall, the results show that MBT residual is a suitable
      support medium for methane oxidation in landfill covers in field conditions in a
      boreal climate.

PMID- 18823645
TI  - Treatment with infliximab plus methotrexate improves anemia in patients with
      rheumatoid arthritis independent of improvement in other clinical outcome
      measures-a pooled analysis from three large, multicenter, double-blind,
      randomized clinical trials.
AB  - OBJECTIVE: To evaluate the effect of antitumor necrosis factor-alpha monoclonal
      antibody infliximab treatment on anemia in patients with rheumatoid arthritis
      (RA). METHODS: Data from patients with RA who received infliximab or placebo in
      the multicenter, placebo-controlled, double-blind, randomized ATTRACT, ASPIRE,
      and START studies were included in this post-hoc, pooled analysis. Infliximab (3
      to 10 mg/kg) was administered every 4 or 8 weeks, and all patients received
      stable doses of methotrexate (MTX). We determined the percentage of anemic
      patients (baseline hemoglobin level <12 g/dL) who had an increase from baseline
      in hemoglobin level greater than or equal to 1 or 2 g/dL or achieved normal
      hemoglobin level at week 22. The association of improvement in anemia with
      improvement in clinical parameters was also evaluated. RESULTS: Among patients
      with anemia at baseline, infliximab plus MTX treatment produced a significantly
      greater mean (standard deviation) increase in hemoglobin level from baseline to
      week 22 (0.74 [1.12], P < 0.0001) than placebo plus MTX (0.30 [0.92]).
      Significantly (P < 0.001) greater proportions of anemic patients treated with
      infliximab plus MTX had either at least a 1 g/dL (40%) or at least a 2 g/dL (12%)
      increase in hemoglobin level from baseline to week 22 or achieved normal
      hemoglobin level (43%) when compared with placebo plus MTX (19, 5, and 28%,
      respectively). Greater improvement in hemoglobin level among infliximab plus MTX
      treated patients was consistently observed across subgroups and in patients
      without clinical response (American College of Rheumatology 20% response
      criteria) at week 22. Multiple regression analysis indicated that the effect of
      infliximab plus MTX on anemia was independent of improvement in disease activity.
      CONCLUSION: Treatment with infliximab plus MTX significantly improved hemoglobin
      level among anemic RA patients when compared with treatment with placebo plus
      MTX, even after adjusting for improvement in disease activity.

PMID- 18823646
TI  - Nonsteroidal anti-inflammatory drugs: adverse effects and their prevention.
AB  - OBJECTIVES: To discuss nonsteroidal anti-inflammatory drugs (NSAIDs), their
      history, development, mode of action, toxicities, strategies for the prevention
      of toxicity, and future developments. METHODS: Medline search for articles
      published up to 2007, using the keywords acetylsalicylic acid, aspirin, NSAIDs,
      cyclooxygenase 2, adverse effects, ulcer, and cardiovascular. RESULTS: NSAIDs are
      1 of the oldest, most successful drugs known to modern medicine. They are
      effective for alleviating pain, fever, and inflammation by inhibiting
      prostaglandin synthesis. Aspirin, by its irreversible inhibition of blood
      platelet function, is also effective in the prevention of cardiovascular disease.
      NSAIDs may cause gastrointestinal ulcers, serious cardiovascular events,
      hypertension, acute renal failure, and worsening of preexisting heart failure.
      These adverse effects may be prevented by limiting NSAID dosage and duration and
      by performing individual risk assessments and treating patients accordingly.
      Those at risk for gastroduodenal ulcers may be treated with concomitant proton
      pump inhibitors, misoprostol and/or COX-2 selective NSAIDs. Those at risk for
      cardiovascular events may be treated with naproxen and a proton-pump inhibitor or
      misoprostol, but should best avoid NSAID use altogether. CONCLUSIONS: Physicians
      should always prescribe the lowest effective dose for the shortest possible time
      and must take into account both the gastrointestinal and the cardiovascular risks
      of individual patients when prescribing NSAIDs.

PMID- 18823647
TI  - Augmentation index and large-artery remodeling in patients with longstanding
      rheumatoid arthritis compared with healthy controls.
AB  - OBJECTIVE: There is growing evidence of premature atherosclerosis in patients
      with rheumatoid arthritis (RA), leading to a higher rate of cardiovascular events
      than in the general population. The augmentation index (AIx), a marker of
      arterial stiffness, is an indicator of vascular function. The aim of the study
      was as follows: (1) to investigate whether AIx is increased in RA patients
      without traditional cardiovascular risk factors and (2) to evaluate whether there
      is an interrelationship with large artery remodeling as ascertained by carotid
      ultrasound. METHODS: Thirty-six RA patients (age, 46.4 +/- 7.7 years; 31 female)
      were recruited. Patients were eligible for analysis if they had no traditional
      cardiovascular risk factors. AIx was assessed noninvasively during pulse wave
      analyses. For large artery remodeling the intima-media thickness (IMT) was
      measured in both common carotid arteries with ultrasound. Results were compared
      with 36 age- and sex-matched controls. RESULTS: AIx was statistically
      significantly higher in RA patients as compared with controls (27.4 +/- 9.4%
      versus 18.4 +/- 9.0%; P < 0.001). In addition, IMT was significantly higher in RA
      patients (0.73 +/- 0.16 mm versus 0.65 +/- 0.12 mm; P = 0.01). In RA patients
      there was a positive correlation between IMT and AIx (r[IMT; AIx] = 0.45; P =
      0.008). CONCLUSION: AIx, a marker of arterial stiffness, as well as IMT, a marker
      of large-artery remodeling, are increased in RA patients without traditional
      cardiovascular risk factors. Measuring AIx might assist in better assessing the
      increased cardiovascular risk in RA patients.

PMID- 18823648
TI  - Duration of anticoagulant therapy for patients with venous thromboembolism.
AB  - In principle, the answer to this question is obvious: "as long as the risk of
      continued therapy is outweighed by the benefit." In practice, determining an
      individual patient's risk of recurrent venous thromboembolism (VTE) without
      warfarin or other vitamin K antagonists is difficult. However, there are many
      factors (both intrinsic and environmental) that can alter the risk of VTE
      recurrence. This paper will discuss evidence and considerations (including the
      issue of bleeding risk) that may be relevant to decisions about duration of
      anticoagulant therapy for patients with VTE.

PMID- 18823649
TI  - Does equal treatment yield equal outcomes? The impact of race on survival in
      epithelial ovarian cancer.
AB  - OBJECTIVE: To determine if race impacts the survival of patients with epithelial
      ovarian cancer in a large academic medical center. METHODS: Demographic and
      clinical-pathologic information from patients treated at the University of
      Chicago from 1992-2007 were analyzed. Continuous variables were analyzed with t
      tests and categorical variables with chi square tests. Survival curves were
      evaluated using Kaplan-Meier methods and Cox proportional hazard models were
      constructed for both overall and disease free survival. RESULTS: 209 women with
      epithelial ovarian cancer were included in the study, 163 (78%) white and 46
      (22%) African American. The baseline demographic characteristics and clinico
      pathologic factors such as disease stage, grading, CA-125 levels, rates of
      optimal debulking (<1 cm residual tumor), platinum sensitivity and American
      Society of Anesthesiologists score (ASA) were similar between the groups. The
      median overall survival for African American women was similar: 37.2 months (95%
      Confidence Interval (CI): 22.5, 52.9) while it was 34.1 months (95% CI: 27.4,
      42.6) for white women. CONCLUSIONS: There is no evidence of a racial disparity in
      either treatment or survival for ovarian cancer patients treated at a large
      academic center. Given that large epidemiologic studies suggested a difference in
      survival between African American and white women, other sources of disparities
      must be sought.

PMID- 18823650
TI  - Role of microRNAs in drug-resistant ovarian cancer cells.
AB  - OBJECTIVES: Chemotherapy is the preferred therapeutic approach for the therapy of
      advanced ovarian cancer, but a successful long-term treatment is prevented by the
      development of drug resistance. Recent works have underlined the involvement of
      non-coding RNAs, microRNAs (miRNAs) in cancer development, with several
      conjectures regarding their possible involvement in the evolution of drug
      resistance. This work was aimed to identify selected microRNAs involved in the
      development of chemoresistance in ovarian cancer. METHODS: High-throughput
      analysis of the miRNA profile in a panel of paclitaxel- (A2780TAX, A2780TC1 and
      A2780TC3) and cisplatin-resistant (A2780CIS) cells was assessed using a
      microarray platform and subsequent validation with qPCR and Northern blots.
      Downstream target validation was performed for miR-130a and the target M-CSF.]
      RESULTS: Six miRNAs (let-7e, miR-30c, miR-125b, miR-130a and miR-335) were always
      diversely expressed in all the resistant cell lines. Let-7e was upregulated in
      A2780TAX cells, while it was downregulated in the other resistant cell lines. The
      opposite phenomenon was obtained for miR-125b, which was downregulated in
      A2780TAX and upregulated in the other cell lines. The miR-30c, miR-130a and miR
      335 were downregulated in all the resistant cell lines, thereby suggesting a
      direct involvement in the development of chemoresistance. Finally downstream
      target validation was proven for the miR-130a, whose downregulation was linked to
      the translational activation of the M-CSF gene, a known resistance factor for
      ovarian cancer. CONCLUSIONS: Our results indicate that ovarian cancer drug
      resistance is associated with a distinct miRNA fingerprint, and miRNA microarrays
      could represent a prognostic tool to monitor the chemotherapy outcome.

PMID- 18823652
TI  - Allergen challenge dose-response slope.

PMID- 18823651
TI  - Chronic granulomatous disease as a risk factor for autoimmune disease.
AB  - Chronic granulomatous disease (CGD) is characterized by recurrent infections and
      granuloma formation. In addition, we have observed a number of diverse autoimmune
      conditions in our CGD population, suggesting that patients with CGD are at an
      elevated risk for development of autoimmune disorders. In this report, we
      describe antiphospholipid syndrome, recurrent pericardial effusion, juvenile
      idiopathic arthritis, IgA nephropathy, cutaneous lupus erythematosus, and
      autoimmune pulmonary disease in the setting of CGD. The presence and type of
      autoimmune disease have important treatment implications for patients with CGD.

PMID- 18823653
TI  - Prevalence of ergot derivatives in natural ryegrass pastures: detection and
      pathogenicity in the horse.
AB  - In the present study, we determined the incidence and effects of season and
      weather on clinical manifestations of endophyte-infected ryegrass toxicity,
      performed chemical detection and pharmacological bioassays on ryegrass extracts,
      and conducted trials on: (i) effects of domperidone or metochlopramide on ovarian
      inactivity induced by endophyte-infected ryegrass; (ii) efficacy of buspirone or
      dihydrochloro phenyl piperazine (m-CPP) for preventing suppressed milk production
      induced by endophyte-infected ryegrass; and (iii) efficacy of domperidone to
      induce ovulation during winter anestrus. Mares with toxicosis had prolonged
      gestation, embryonic losses, dystocia, poor mammary gland development, low milk
      production, prolonged uterine involution, and suppressed ovarian activity. Foals
      had respiratory failure, abnormalities of the skin, umbilicus, bone, and muscle,
      failure to thrive, blindness, testicular atrophy, and decreased serum total
      immunoglobulin concentrations. Endophyte-infected ryegrass and the incidence of
      toxicosis were correlated (r=0.861, P=0.03). Ergot alkaloids were not detected in
      extracts of endophyte-infected ryegrass by either thin-layer chromatography or
      spectrophotometry, but their presence was inferred in bioassays of extracts (dose
      related increases in the contractile response of rat uterus). Mares given
      metoclopropamide (0.6 mg/kg/d), given orally every 8h for up to 7d) ovulated
      earlier (4-7d vs. 15-18d, P<0.001) than those given domperidone (1.1mg/kg/d)
      orally for up to 18d). Although both metoclopropamide and domperidone induced
      milk production, the latter did not induce ovarian cyclicity in healthy mares
      during seasonal anestrus. Based on these findings, we inferred that endophyte
      infected ryegrass is associated with ergot alkaloid intoxication in horse.

PMID- 18823654
TI  - Glucose homeostasis during canine pregnancy: Insulin resistance, ketosis, and
      hypoglycemia.
AB  - Through a variety of mechanisms, pregnancy causes insulin resistance, which
      suppresses the intracellular transport of glucose and increases blood glucose
      concentrations. In the extreme, gestational diabetes (GDM) mellitus may develop.
      In addition to insulin resistance, pregnant bitches have decreased ability to
      produce glucose via gluconeogenesis, glycogenolysis and lipolysis, because the
      normal multi-factorial responses to hypoglycemia are blunted late in pregnancy.
      Simply fasting late-pregnant bitches is sufficient to cause blood glucose and
      insulin concentrations to decrease and ketones to increase. The purpose of this
      paper is to review the clinical implications of pregnancy-associated changes in
      glucose homeostasis in bitches.

PMID- 18823655
TI  - Auditory word comprehension impairment in acute stroke: relative contribution of
      phonemic versus semantic factors.
AB  - Auditory word comprehension was assessed in a series of 289 acute left hemisphere
      stroke patients. Participants decided whether an auditorily presented word
      matched a picture. On different trials, words were presented with a matching
      picture, a semantic foil, or a phonemic foil. Participants had significantly more
      trouble with semantic foils across all levels of impairment.

PMID- 18823657
TI  - DIRECT new treatments for diabetic retinopathy.

PMID- 18823656
TI  - Effect of candesartan on prevention (DIRECT-Prevent 1) and progression (DIRECT
      Protect 1) of retinopathy in type 1 diabetes: randomised, placebo-controlled
      trials.
AB  - BACKGROUND: Results of previous studies suggest that renin-angiotensin system
      blockers might reduce the burden of diabetic retinopathy. We therefore designed
      the DIabetic REtinopathy Candesartan Trials (DIRECT) Programme to assess whether
      candesartan could reduce the incidence and progression of retinopathy in type 1
      diabetes. METHODS: Two randomised, double-blind, parallel-design, placebo
      controlled trials were done in 309 centres worldwide. Participants with
      normotensive, normoalbuminuric type 1 diabetes without retinopathy were recruited
      to the DIRECT-Prevent 1 trial and those with existing retinopathy were recruited
      to DIRECT-Protect 1, and were assigned to candesartan 16 mg once a day or
      matching placebo. After 1 month, the dose was doubled to 32 mg. Investigators and
      participants were unaware of the treatment allocation status. The primary
      endpoints were incidence and progression of retinopathy and were defined as at
      least a two-step and at least a three-step increase on the Early Treatment
      Diabetic Retinopathy Study (ETDRS) scale, respectively. These trials are
      registered with ClinicalTrials.gov, numbers NCT00252733 for DIRECT-Prevent 1 and
      NCT00252720 for DIRECT-Protect 1. FINDINGS: 1421 participants (aged 18-50 years)
      were randomly assigned to candesartan (n=711) or to placebo (n=710) in DIRECT
      Prevent 1, and 1905 (aged 18-55 years) to candesartan (n=951) or to placebo
      (n=954) in DIRECT-Protect 1. Incidence of retinopathy was seen in 178 (25%)
      participants in the candesartan group versus 217 (31%) in the placebo group.
      Progression of retinopathy occurred in 127 (13%) participants in the candesartan
      group versus 124 (13%) in the placebo group. Hazard ratio (HR for candesartan vs
      placebo) was 0.82 (95% CI 0.67-1.00, p=0.0508) for incidence of retinopathy and
      1.02 (0.80-1.31, p=0.85) for progression of retinopathy. The post-hoc outcome of
      at least a three-step increase for incidence yielded an HR of 0.65 (0.48-0.87,
      p=0.0034), which was attenuated but still significant after adjustment for
      baseline characteristics (0.71, 0.53-0.95, p=0.046). Final ETDRS level was more
      likely to have improved with candesartan treatment in both DIRECT-Prevent 1 (odds
      1.16, 95% CI 1.05-1.30, p=0.0048) and DIRECT-Protect 1 (1.12, 95% CI 1.01-1.25,
      p=0.0264). Adverse events did not differ between the treatment groups.
      INTERPRETATION: Although candesartan reduces the incidence of retinopathy, we did
      not see a beneficial effect on retinopathy progression.

PMID- 18823659
TI  - Culture on electrospun polyurethane scaffolds decreases atrial natriuretic
      peptide expression by cardiomyocytes in vitro.
AB  - The function of the mammalian heart depends on the functional alignment of
      cardiomyocytes, and controlling cell alignment is an important consideration in
      biomaterial design for cardiac tissue engineering and research. The physical cues
      that guide functional cell alignment in vitro and the impact of substrate-imposed
      alignment on cell phenotype, however, are only partially understood. In this
      report, primary cardiac ventricular cells were grown on electrospun,
      biodegradable polyurethane (ES-PU) with either aligned or unaligned microfibers.
      ES-PU scaffolds supported high-density cultures and cell subpopulations remained
      intact over two weeks in culture. ES-PU cultures contained electrically-coupled
      cardiomyocytes with connexin-43 localized to points of cell:cell contact. Multi
      cellular organization correlated with microfiber orientation and aligned
      materials yielded highly oriented cardiomyocyte groupings. Atrial natriuretic
      peptide, a molecular marker that shows decreasing expression during ventricular
      cell maturation, was significantly lower in cultures grown on ES-PU scaffolds
      than in those grown on tissue culture polystyrene. Cells grown on aligned ES-PU
      had significantly lower steady state levels of ANP and constitutively released
      less ANP over time indicating that scaffold-imposed cell organization resulted in
      a shift in cell phenotype to a more mature state. We conclude that the physical
      organization of microfibers in ES-PU scaffolds impacts both multi-cellular
      architecture and cardiac cell phenotype in vitro.

PMID- 18823660
TI  - A comparative study of proliferation and osteogenic differentiation of adipose
      derived stem cells on akermanite and beta-TCP ceramics.
AB  - This study investigated the in vitro effects of akermanite, a new kind of Ca-, Mg
      , Si-containing bioceramic, on the attachment, proliferation and osteogenic
      differentiation of human adipose-derived stem cells (hASCs). Parallel comparison
      of the cellular behaviors of hASCs on the akermanite was made with those on beta
      tricalcium phosphate (beta-TCP). Scanning electron microscope (SEM) observation
      and fluorescent DiO labeling were carried out to reveal the attachment and growth
      of hASCs on the two ceramic surfaces, while the quantitative assay of cell
      proliferation with time was detected by DNA assay. Osteogenic differentiation of
      hASCs cultured on the akermanite and beta-TCP was assayed by ALP expression and
      osteocalcin (OCN) deposition, which was further confirmed by Real-time PCR
      analysis for markers of osteogenic differentiation. It was shown that hASCs
      attached and spread well on the akermanite as those on beta-TCP, and similar
      proliferation behaviors of hASCs were observed on the two ceramics. Both of them
      exhibited good compatibility to hASCs with only minor cytotoxicity as compared
      with the tissue culture plates. Interestingly, the osteogenic differentiation of
      hASCs could be enhanced on the akermanite compared with that on the beta-TCP when
      the culture time was extended to approximately 10 days. Thus, it can be
      ascertained that akermanite ceramics may serve as a potential scaffold for bone
      tissue engineering.

PMID- 18823661
TI  - Demethylating agent 5-aza-2'-deoxycytidine activates HLA-G expression in human
      leukemia cell lines.
AB  - HLA-G is a non-classical HLA class I antigen primarily expressed in the
      extravillous cytotrophoblast. HLA-G can also be expressed at some pathological
      circumstances and may thus contribute to inhibition of efficient immune
      responses. Complex regulation of HLA-G expression also involves epigenetic
      mechanisms as DNA methylation. Here we demonstrate that treatment with
      demethylating agent 5-aza-2'-deoxycytidine (AdC) resulted in HLA-G transcription
      in 18 out of 20 examined leukemia cell lines. HLA-G protein synthesis was
      detected in 10 cell lines expressing significant level of HLA-G transcripts
      following AdC treatment.

PMID- 18823662
TI  - Road traffic noise, sensitivity, annoyance and self-reported health--a structural
      equation model exercise.
AB  - The proposed effect of road traffic noise on hypertension and ischemic heart
      disease finds mixed empirical support. One problem with many studies is that the
      directions of the causal relationships are not identified. This is often the case
      when cross-sectional data and multivariate regression models are utilised. The
      aim of the study was to explore the relationship between road traffic noise and
      health. More specifically the relationships between noise complaints, noise
      sensitivity and subjectively reported hypertension and heart problems were
      investigated. 1842 respondents in Oslo, Norway were interviewed about their
      experience of the local environment and their subjective health complaints. The
      interviews were conducted as part of two surveys. Individual measures of air
      pollution (NO(2)) and noise (Lden) were calculated. The data were analysed using
      Structural Equation Models. Only sensitivity to noise is related to hypertension
      and chest pain. No relationships between noise exposure and health complaints
      were identified. Rather than noise being the causal agent leading to health
      problems, the results suggest that the noise-health relationships in these
      studies may be spurious. It is conceivable that individual vulnerability is
      reflected both in ill health and in being sensitive to noise. The benefit of
      including more contextual variables in a model of noise-health relationships is
      supported.

PMID- 18823663
TI  - Persistent organochlorine compounds in peregrine falcon (Falco peregrinus) eggs
      from South Greenland: levels and temporal changes between 1986 and 2003.
AB  - Thirty-seven addled peregrine falcon eggs collected in South Greenland between
      1986 and 2003 were analysed for their content of the organochlorine compounds
      polychlorinated biphenyls (PCBs), dichlorodiphenyl tricloroethane (DDT) and its
      degradation products, hexachlorocyclohexane (HCH) isomers and hexachlorobenzene
      (HCB). PCBs and DDT (including metabolites) were by far the most abundant OC
      groups, with median concentrations of 55 and 40 microg/g lw, respectively. The
      concentrations were high in an Arctic context, but similar to previously reported
      levels from Alaska and Norway and slightly lower than concentrations measured in
      eggs from industrialised regions. Geographical differences may be of importance,
      considering the migration of peregrine falcons and their prey. SigmaHCH and HCB
      had median concentrations of 0.39 and 0.17 microg/g lw, respectively. On average,
      DDE accounted for 97% of SigmaDDT, but was below critical levels for eggshell
      thinning. All compound groups showed a weak decreasing trend over the study
      period, which was statistically significant for HCB and close to being
      significant for SigmaHCH. The weak decrease of SigmaPCB and SigmaDDT is different
      from other time trend studies from Greenland, usually showing a more pronounced
      decrease in the beginning of the study period, followed by a certain
      stabilisation in recent years.

PMID- 18823658
TI  - Effect of candesartan on progression and regression of retinopathy in type 2
      diabetes (DIRECT-Protect 2): a randomised placebo-controlled trial.
AB  - BACKGROUND: Diabetic retinopathy remains a leading cause of visual loss in people
      of working age. We examined whether candesartan treatment could slow the
      progression and, secondly, induce regression of retinopathy in people with type 2
      diabetes. METHODS: We did a randomised, double-blind, parallel-group, placebo
      controlled trial in 309 centres worldwide. We recruited normoalbuminuric,
      normotensive, or treated hypertensive people with type 2 diabetes with mild to
      moderately severe retinopathy and assigned them to candesartan 16 mg once a day
      or placebo. After a month, the dose was doubled to 32 mg once per day.
      Investigators and patients were unaware of the treatment allocation status.
      Progression of retinopathy was the primary endpoint, and regression was a
      secondary endpoint. Analysis was by intention to treat. The trial is registered
      with ClinicalTrials.gov, number NCT00252694. FINDINGS: 1905 participants (aged 37
      75 years) were randomised to candesartan (n=951) or placebo (n=954). 161 (17%)
      patients in the candesartan group and 182 (19%) in the placebo group had
      progression of retinopathy by three steps or more on the Early Treatment Diabetic
      Retinopathy Study scale. The risk of progression of retinopathy was non
      significantly reduced by 13% in patients on candesartan compared with those on
      placebo (hazard ratio [HR] 0.87, 95% CI 0.70-1.08, p=0.20). Regression on active
      treatment was increased by 34% (1.34, 1.08-1.68, p=0.009). HRs were not
      attenuated by adjustment for baseline risk factors or changes in blood pressure
      during the trial. An overall change towards less severe retinopathy by the end of
      the trial was observed in the candesartan group (odds 1.17, 95% CI 1.05-1.30,
      p=0.003). Adverse events did not differ between the treatment groups.
      INTERPRETATION: Treatment with candesartan in type 2 diabetic patients with mild
      to moderate retinopathy might induce improvement of retinopathy.

PMID- 18823664
TI  - Expression of biologically active recombinant porcine interleukin-12 from
      Escherichia coli.
AB  - The control of viral infections is of critical importance to livestock industries
      worldwide and is highlighted by costly infection outbreaks, such as that seen
      with foot and mouth disease virus. To ameliorate the impact of increasing
      problems with viral infections, new vaccine and anti-viral strategies are
      required and a greater understanding of the anti-viral response is essential.
      Furthermore, in pigs, evidence is still being gathered on the components of a
      defined anti-viral immune response. However, this has been greatly improved by
      the recent cloning and expression of critical cytokines involved in the anti
      viral response. To assess the use of recombinant porcine interleukin-12 (rPoIL
      12) as an immunotherapeutic and immunomodulator of swine, we have cloned and
      expressed rPoIL-12 as a single-chain fusion protein from Esherichia coli (E.
      coli). The fusion encodes the p40 and p35 subunits, linked by a glycine-serine
      linker and expressed as a C-terminal 6xHis tagged protein. rPoIL-12 stimulated
      the proliferation of human lymphoblasts and its activity on porcine cells was
      demonstrated by the ability of rPoIL-12 to increase the mRNA expression of
      porcine interleukin-18 receptor-alpha (poIL-18Ralpha) from porcine peripheral
      blood mononuclear cells (PoPMBCs). This data supports the inclusion of E. coli
      produced rPoIL-12 in immunomodulation strategies in the pig.

PMID- 18823665
TI  - Emerging roles for two-pore-domain potassium channels and their potential
      therapeutic impact.
AB  - A distinct gene family of widely distributed and well-modulated two-pore-domain
      background potassium (K(2P)) channels establish resting membrane potential and
      cell excitability. By using new mouse models in which K(2P)-channel genes are
      deleted, the contributions of these channels to important physiological functions
      are now being revealed. Here, we highlight results of recent studies using mice
      deleted for K(2P)-channel subunits that uncover physiological functions of these
      channels, mostly those of the TASK and TREK subgroup. Consistent with activation
      of these K(2P) channels by volatile anesthetics, TASK-1, TASK-3 and TREK-1
      contribute to anesthetic-induced hypnosis and immobilization. The acid-sensitive
      TASK channels are not required for brainstem control of breathing by CO(2) or pH,
      despite widespread expression in respiratory-related neurons. TASK channels are
      necessary, however, for homeostatic regulation of adrenal aldosterone secretion.
      The heat-, stretch- and lipid-activated TREK-1 channels contribute to temperature
      and mechanical pain sensation, neuroprotection by polyunsaturated fatty acids
      and, unexpectedly, mood regulation. The alkaline-activated TASK-2 channel is
      necessary for HCO(3)(-) reabsorption and osmotic volume regulation in kidney
      proximal tubule cells. Development of compounds that selectively modulate K(2P)
      channels is crucial for verifying these results and assessing the efficacy of
      therapies targeting these interesting channels.

PMID- 18823666
TI  - The role of fluctuations in perception.
AB  - Noise contributed by the probabilistic spiking times of neurons has an important
      and advantageous role in brain function. We go beyond the deterministic noiseless
      description of the dynamics of cortical networks and show how the properties of
      the system are influenced by the spiking noise. We review here recent results
      that show the direct link between brain activity and psychophysically quantified
      behaviors during a somatosensory detection task. We focus on the following
      remarkable observation in this somatosensory task: when a near-threshold stimulus
      is presented, a sensory percept may or may not be produced. These perceptual
      judgments are believed to be determined by the fluctuation in activity of early
      sensory cortices. We show, however, that the behavioral outcomes associated with
      near-threshold stimuli depend on the neuronal fluctuations of more central areas
      to early somatosensory cortices. Furthermore, we show that the behavioral
      correlate of perceptual detection is given by a noise-driven transition in a
      multistable neurodynamical system. Thus, neuronal fluctuations can be an
      advantage for brain processing because they lead to probabilistic behavior in
      decision making in this and other sensory tasks.

PMID- 18823667
TI  - Hepatic transcriptomic profiles of European flounder (Platichthys flesus) from
      field sites and computational approaches to predict site from stress gene
      responses following exposure to model toxicants.
AB  - Genomic technologies offer opportunities to gain a more global assessment of the
      health status of an organism through an understanding of the functional pathways
      that are responding to pollutant exposure. We have developed a 13,000 clone cDNA
      toxicogenomics microarray for Platichthys flesus, the European flounder (EU
      GENIPOL Project). We aimed to distinguish the origins of flounder taken from six
      sampling sites of different pollution status in Northern Europe according to
      their hepatic gene expression profile using bioinformatic approaches. To
      determine which gene expression differences may relate to pollutant impact, we
      have completed complementary laboratory exposures of flounder to selected
      toxicants and determined the associated gene expression profiles. Using
      multivariate variable selection coupled with a statistical modelling procedure
      (GALGO) we can predict geographical site but the accuracy is limited to specific
      sites. The search space for a combination of genes that effectively predicts
      class membership is very large, however, by combining the signatures derived from
      acute laboratory exposure to individual chemicals to limit the search space, a
      very accurate model for classification of all the different environmental sites
      was achieved. The final model utilised the expression profiles of 16 clones and
      validation with a qPCR array comprising these genes correctly assigned the site
      of origin for fish obtained from three of the sites in an independent sampling.
      These data would imply that the gene expression fingerprints obtained with these
      arrays are primarily attributable to variations in chemical pollutant responses
      at the different sites, indicating their potential utility in environmental
      impact assessment.

PMID- 18823668
TI  - Sulfhydryl systems are a critical factor in the zebrafish developmental toxicity
      of the dithiocarbamate sodium metam (NaM).
AB  - Dithiocarbamates (DTCs) are sulfhydryls (thiol)-containing compounds, often
      associated with metals, and have both antioxidant and pro-oxidant abilities
      depending on the compound, experimental system and condition. In this study we
      investigated whether cell death plays a role in the manifestation of DTC-induced
      notochord distortions in the developing zebrafish and if thiol-containing
      compounds or antioxidants could modify this developmental toxicity. Sodium metam
      (NaM) induced notochord distortions could not be protected with the antioxidants
      ascorbic acid, trolox (synthetic vitamin E) or lipoic acid. However, NaM-induced
      distortions could be protected with co-exposure to glutathione or N-Acetyl
      Cysteine. Staggering the NaM and glutathione exposures in consecutive 10h
      developmental windows also resulted in protection. There were no discernable
      changes in TUNEL positive cells, a marker of apoptotic cells, at 24h post
      fertilization (hpf) in NaM, dimethyl-dithiocarbamate, carbon disulfide, or
      neocuproine exposed embryos. Live NaM-exposed embryos incubated with acridine
      orange, a general stain for cell death, for 1h beginning at 11, 18 and 24hpf
      showed clusters of stained nuclei near the somitogenic front but not in the cells
      making up the notochord. Overall, induction of apoptotic pathways and widespread
      cell death are not involved in the manifestation of the adverse developmental
      outcomes following NaM exposure. However, cellular thiol status or critical
      sulfhydryl moieties are important considerations in the mechanisms of DTC
      developmental toxicity.

PMID- 18823669
TI  - Endothelial progenitor cells and cardiovascular homeostasis: clinical
      implications.
AB  - Emerging evidences indicate that endothelial progenitor cells (EPCs) actively
      contribute in regulating cardiovascular homeostasis, and interest is growing for
      possible future diagnostic and therapeutic applications in the cardiovascular
      arena. In the present clinically-oriented review, special attention was given to
      the clinical implications of the potential of EPCs to test and strengthen the
      capacity of the organism to challenge atherosclerosis, vascular remodelling and
      ischemia. Accumulating data suggest that the vasculo-protective functions of EPCs
      may be used as cellular biomarkers for endothelial damage, or may be
      pharmacologically modulated to enhance the body's defence to atherosclerosis.
      Furthermore, biomedical engineering and cell transplantation open new scenarios
      to reverse vascular and graft remodelling and achieve therapeutic angiogenesis in
      limb and heart ischemia. However, a number of unsolved issues remain to be
      exploited, such as the identification of the true identity of EPCs and a better
      characterization of their role in vascular homeostasis under normal and
      pathologic conditions.

PMID- 18823670
TI  - Future costs in economic evaluation. A comment on Lee.
AB  - In a recent article in this journal Lee argued that indirect medical costs should
      be ignored in economic evaluations. To reach this conclusion, Lee uses an
      unrealistic and uncommon budget constraint. This comment highlights a number of
      methodological problems in Lee's analysis. Moreover, it highlights that looking
      at current practice of economic evaluation, Lee's model implies the inclusion
      rather than the exclusion of indirect medical costs.

PMID- 18823671
TI  - Identification of non-linear microbial inactivation kinetics under dynamic
      conditions.
AB  - In this study dynamic microbial inactivation experiments are exploited for
      performing parameter identification of a non-linear microbial model. For that
      purpose microbial inactivation data are produced and a differential equation
      exhibiting a shoulder and a loglinear phase is employed. The derived parameter
      estimates from this method were used to perform predictions on an independent
      experimental set at fluctuating temperature. Joint confidence regions and
      asymptotic confidence intervals of the estimated parameters were compared with
      previous studies originating from parameter identification under isothermal
      conditions. The developed approach can provide more reliable estimates for
      realistic conditions compared to the usual or standard two step approach.

PMID- 18823672
TI  - Enhanced short-term improvement of insulin response to a low-caloric diet in
      obese carriers the Gly482Ser variant of the PGC-1alpha gene.
AB  - AIM: The Gly482Ser missense mutation of the transcriptional coactivator,
      peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha)
      has been involved in insulin function impairments, with conflicting results. The
      current study investigated the relationships of carrying this polymorphism with
      insulin resistance (IR) during a short-term weight-loss and the subsequent weight
      follow-up. METHODS: The Gly482Ser was genotyped in 180 Spanish volunteers [body
      mass index: 31.4+/-3.2kg/m(2); age: 35+/-5 years]. Specific phenotypical
      measurements were determined at baseline, following an 8-week low-calorie diet
      (LCD) as well as after 6-month and 1-year of follow-up. RESULTS: At baseline the
      Ser482Ser genotype was associated with higher HOMA-IR and insulin concentrations
      than the other genotypes (p<0.05), which was accompanied by an increased higher
      risk of IR (OR: 2.97; 95% CI: 1.24-7.15). After following the LCD, such increased
      risk of insulin insensitivity in Ser482Ser carriers was toned down (p>0.05). This
      outcome was sustained after 6-month and 1-year of follow-up (p>0.05).
      CONCLUSIONS: These data show an increased risk of IR in obese carrying the
      rs8192673 Ser482Ser genotype. This risk was markedly reduced by an energy
      restricted diet, which was sustained 6 months and 1 year after the diet therapy.
      This observation allows identifying obese subjects who might personally profit
      most from an energy-restrictive treatment concerning insulin response and lead to
      more individualized prognostic and therapeutic decisions.

PMID- 18823673
TI  - Can diabetes medication be reduced in elderly patients? An observational study of
      diabetes drug withdrawal in nursing home patients with tight glycaemic control.
AB  - AIM: To explore the feasibility of withdrawal of diabetes medication in elderly
      patients with HbA1c<or=6.0%. METHODS: HbA1c was measured in 98 patients with
      known diabetes in 17 nursing homes in Sweden. Thirty-two subjects with HbA1c
      <or=6.0% participated in the drug withdrawal study. After measuring plasma
      glucose on 3 consecutive days, diabetes drugs were reduced, i.e. complete
      withdrawal of oral anti-diabetic drugs (OADs), complete insulin withdrawal when
      doses were <or=20units/day and reduced by half in patients on more than
      20units/day. RESULTS: We identified 31 episodes of plasma glucose <or=4.4mmol/l,
      most of them nocturnal (n=17). Mean HbA1c was 5.2+/-0.4% compared to 7.1+/-1.6%
      in the non-intervention group. Three months after the diabetes drug
      discontinuation, 24 patients (75%) remained in the intervention group and mean
      HbA1c was then 5.8.+/-0.9%. Six months after baseline investigation mean HbA1c in
      the intervention group was 5.8+/-1.1% compared with 6.6+/-1.4% in the non
      intervention group. CONCLUSIONS: Hypoglycaemic events are common among elderly
      patients with type 2 diabetes. The withdrawal of diabetes medication in elderly
      with tight glycaemic control is safe and may decrease the risk for hypoglycaemia.

PMID- 18823674
TI  - International perspectives on the cost-effectiveness of tandem mass spectrometry
      for rare metabolic conditions.
AB  - OBJECTIVES: To examine and evaluate the economic evidence regarding the use of
      tandem mass spectrometry (MS/MS) for the detection of rare metabolic conditions
      in neonates, and then to consider the transferability of these national-level
      results to other decision-making contexts. METHODS: A systematic literature
      review was undertaken, identifying papers published between January 1997 and
      March 2008. Thirteen unique cost-effectiveness evaluations were identified and
      appraised for comparability and transferability of results across settings.
      RESULTS: The primary outcome measure was usually life years gained (LYG) or
      quality-adjusted life years gained (QALY). The incremental cost-effectiveness
      ratios (ICER) presented were generally supportive of MS/MS, but showed
      considerable variation. Differences in assumptions made regarding prevalence and
      prognosis played a significant role in this variation. CONCLUSIONS: Differences
      in study structure, the approach to costing, the choice of intervention, control
      and outcome measure, and the limit of studies to developed countries makes
      international generalisation of the cost-effectiveness evidence difficult. The
      importance of assumptions regarding disease progression and subsequent health
      care utilisation suggests that further work needs to consider the importance of
      longer-term follow-up.

PMID- 18823675
TI  - Child head injury criteria investigation through numerical simulation of real
      world trauma.
AB  - Finite element modelling has been used for decades in the study of adult head
      injury biomechanics and determination of injury criteria. Interest is recently
      growing in investigation on pediatric head injury which requires elaboration of
      biofidelic models that take into account child's head particularities in terms of
      size, geometry, and mechanical properties. In this study, a finite element model
      of a 3-year-old child head is proposed. The model is reconstructed from real CT
      scan images and mechanical properties are extracted from available data in the
      literature. A large number of real accidents (25 falls) are reconstructed with
      proposed model using different brain constitutive relationships in order to
      investigate their influence on model response. Mechanical output parameters (HIC,
      pressure, shearing stress) are calculated from these simulations. Statistical
      analysis was performed in order to evaluate predictive capability of the
      parameters. Von Mises stress appears to be clearly the most predictive
      parameters, allowing clear distinction between injured and non-injured cases. To
      the authors' knowledge, this study proposes for the first time a statistically
      based neurological injury criterion for a pediatric population using finite
      element modelling.

PMID- 18823676
TI  - Immunohistochemical expression of BCRP and ERCC1 in biopsy specimen predicts
      survival in advanced non-small-cell lung cancer treated with cisplatin-based
      chemotherapy.
AB  - PURPOSE: The aim of this study was to determine the prognostic value of
      expression of ATP binding cassette (ABC) transporter proteins and DNA repair gene
      proteins by immunohistochemically staining tumor biopsy specimens from patients
      with advanced non-small-cell lung cancer (NSCLC) being treated with platinum
      based chemotherapy. EXPERIMENTAL DESIGN: Expression of ABC transporter proteins,
      including BCRP (breast cancer resistance protein) and MRP2 (multidrug resistance
      proteins 2), and the DNA-repair-related proteins, ERCC1 (excision repair cross
      complementation group 1) and BRCA1 (breast cancer type 1 susceptibility protein)
      was assessed immunohistochemically in 156 tumor samples from untreated stage IV
      NSCLC patients. All of the patients had received platinum-based chemotherapy.
      Response to chemotherapy, progression-free survival (PFS), and overall survival
      were compared in relation to expression of each of the proteins and to
      clinicopathological factors. RESULTS: High ERCC1 expression was associated with
      short survival (237 days vs. 453 days, log-rank P = 0.03), but not with response
      to chemotherapy or PFS. And high BCRP expression was associated with short
      survival (214 days vs. 412 days, log-rank P = 0.02) but not with response to
      chemotherapy or PFS. Multivariate analysis confirmed that negativity for the
      expression of BCRP tends to be an independent variable related to overall
      survival (P = 0.06). CONCLUSIONS: This study examined ERCC1 and BCRP expression
      in biopsy specimens as candidates for predictors of the survival of patients with
      advanced NSCLC treated with platinum-based chemotherapy.

PMID- 18823677
TI  - Missing inaction: the dangers of ignoring missing data.
AB  - The most common approach to dealing with missing data is to delete cases
      containing missing observations. However, this approach reduces statistical power
      and increases estimation bias. A recent study shows how estimates of heritability
      and selection can be biased when the 'invisible fraction' (missing data due to
      mortality) is ignored, thus demonstrating the dangers of neglecting missing data
      in ecology and evolution. We highlight recent advances in the procedures of
      handling missing data and their relevance and applicability.

PMID- 18823678
TI  - Phylogenetic analysis of community assembly and structure over space and time.
AB  - Evolutionary ecologists are increasingly combining phylogenetic data with
      distributional and ecological data to assess how and why communities of species
      differ from random expectations for evolutionary and ecological relatedness. Of
      particular interest have been the roles of environmental filtering and
      competitive interactions, or alternatively neutral effects, in dictating
      community composition. Our goal is to place current research within a dynamic
      framework, specifically using recent phylogenetic studies from insular
      environments to provide an explicit spatial and temporal context. We compare
      communities over a range of evolutionary, ecological and geographic scales that
      differ in the extent to which speciation and adaptation contribute to community
      assembly and structure. This perspective allows insights into the processes that
      can generate community structure, as well as the evolutionary dynamics of
      community assembly.

PMID- 18823679
TI  - Parasites as predators: unifying natural enemy ecology.
AB  - Parasitism and predation have long been considered analogous interactions. Yet by
      and large, ecologists continue to study parasite-host and predator-prey ecology
      separately. Here we discuss strengths and shortcomings of the parasite-as
      predator analogy and its potential to provide new insights into both fields.
      Developments in predator-prey ecology, such as temporal risk allocation and
      associational resistance, can drive new hypotheses for parasite-host systems.
      Concepts developed in parasite-host ecology, such as threshold host densities and
      phylodynamics, might provide new ideas for predator-prey ecology. Topics such as
      trait-mediated indirect effects and enemy-mediated facilitation provide
      opportunities for the two fields to work together. We suggest that greater
      unification of predator-prey and parasite-host ecology would foster advances in
      both fields.

PMID- 18823680
TI  - Mechanisms of long-distance seed dispersal.
AB  - Growing recognition of the importance of long-distance dispersal (LDD) of plant
      seeds for various ecological and evolutionary processes has led to an upsurge of
      research into the mechanisms underlying LDD. We summarize these findings by
      formulating six generalizations stating that LDD is generally more common in open
      terrestrial landscapes, and is typically driven by large and migratory animals,
      extreme meteorological phenomena, ocean currents and human transportation, each
      transporting a variety of seed morphologies. LDD is often associated with unusual
      behavior of the standard vector inferred from plant dispersal morphology, or
      mediated by nonstandard vectors. To advance our understanding of LDD, we advocate
      a vector-based research approach that identifies the significant LDD vectors and
      quantifies how environmental conditions modify their actions.

PMID- 18823681
TI  - Increased aging in primary muscle cultures of sporadic inclusion-body myositis.
AB  - Ageing is thought to participate to the pathogenesis of sporadic inclusion-body
      myositis (s-IBM). Although the regenerative potential of s-IBM muscle is reduced
      in vivo, age-related abnormalities of satellite cells possibly accounting for the
      decline of muscle repair have not been demonstrated. Here we show that
      proliferation rate and clonogenicity of s-IBM myoblasts are significantly lower
      and doubling time is longer than normal age-matched controls, indicating that
      proliferative capacity of s-IBM muscles becomes exhausted earlier. Telomere
      shortening is detected in s-IBM cells suggesting premature senescence.
      Differently from controls, s-IBM myoblasts show increased active beta-catenin
      mainly localized within myonuclei, indicating active Wnt stimulation. After many
      rounds of muscle growth, only s-IBM myoblasts accumulate congophilic inclusions
      and immunoreactive Abeta(1-40) deposits. Therefore, s-IBM myoblasts seem to have
      a constitutively impaired regenerative capacity and the intrinsic property, upon
      sufficient aging in vitro, to accumulate Abeta. Our results might be valuable in
      understanding molecular mechanisms associated with muscle aging underlying the
      defective regeneration of s-IBM muscle and provide new clues for future
      therapeutic strategies.

PMID- 18823682
TI  - Study of soil-plant transfer of 226Ra under greenhouse conditions.
AB  - A soil-plant transfer study was performed using soil from a former uranium ore
      processing factory in South Bohemia. We present the results from greenhouse
      experiments which include estimates of the time required for phytoremediation.
      The accumulation of (226)Ra by different plant species from a mixture of garden
      soil and contaminated substrate was extremely variable, ranging from 0.03 to 2.20
      Bq (226)Ra/g DW. We found differences in accumulation of (226)Ra between plants
      from the same genus and between cultivars of the same plant species. The results
      of (226)Ra accumulation showed a linear relation between concentration of (226)Ra
      in plants and concentration of (226)Ra in soil mixtures. On the basis of these
      results we estimated the time required for phytoremediation, but this appears to
      be too long for practical purposes.

PMID- 18823683
TI  - Eagle's syndrome after fracture of the elongated styloid process.
AB  - A case is reported of a patient presenting to clinic after a sudden spontaneous
      'cracking' sensation in the jugulo-digastric region. This proved, following
      clinical and radiological investigation, to be a fractured elongated styloid
      process(ESP). This extraordinary presentation of Eagle's syndrome has not
      previously been published.

PMID- 18823684
TI  - Cystatin C and carotid intima-media thickness in asymptomatic adults: the Multi
      Ethnic Study of Atherosclerosis (MESA).
AB  - BACKGROUND: Persons with early kidney disease have an increased risk of
      cardiovascular events and mortality, but the importance of accelerated
      atherosclerosis in promoting these outcomes is unclear. We therefore explored
      whether serum cystatin C level is associated with carotid intima-media thickness
      (IMT) in ambulatory adults without clinical heart disease. STUDY DESIGN: Cross
      sectional study. SETTING & PARTICIPANTS: We evaluated 6,557 ethnically diverse
      persons free of clinical cardiovascular disease aged 45 to 84 years at the
      baseline visit of the Multi-Ethnic Study of Atherosclerosis. PREDICTORS: Kidney
      function was estimated by using 2 methods: serum cystatin C level and estimated
      glomerular filtration rate, based on creatinine and cystatin C levels. OUTCOMES &
      MEASUREMENTS: Study outcomes were internal and common carotid IMT, measured by
      using high-resolution B-mode ultrasound. Multivariate linear and logistic
      regressions were used to evaluate the independent association of kidney function
      with carotid IMT. RESULTS: In unadjusted linear analysis, each SD (0.23 mg/L)
      greater cystatin C level was associated with 0.091-mm greater internal carotid
      IMT (P < 0.001), but this association was diminished by 70% after adjustment for
      age, sex, and race/ethnicity (0.027 mm; P < 0.001) and was no longer significant
      after adjustment for cardiovascular risk factors (0.005 mm; P = 0.5). Similarly,
      the strong unadjusted associations of cystatin C level with common carotid IMT
      disappeared after adjustment. Chronic kidney disease, defined by using either
      creatinine level or cystatin C-based estimated glomerular filtration rate less
      than 60 mL/min/1.73 m(2), had no independent association with internal and common
      carotid IMT. LIMITATIONS: There were few participants with severe kidney disease.
      CONCLUSIONS: Cystatin C level had no independent association with carotid IMT in
      a population free of clinical heart disease. This observation suggests that
      accelerated atherosclerosis is unlikely to be the primary mechanism explaining
      the independent association of cystatin C level with cardiovascular risk.

PMID- 18823685
TI  - Rituximab treatment of fibrillary glomerulonephritis.
AB  - Fibrillary glomerulonephritis belongs to a group of disorders characterized by
      pathogenic deposition of fibrils in glomeruli. This glomerulopathy tends to
      progress to end-stage kidney disease, and there currently are no treatments of
      proven benefit, including corticosteroids and cytotoxic agents. Because the
      glomerular deposits contain an immunoglobulin component, it was postulated that
      anti-B-cell therapy with rituximab, an anti-CD20 monoclonal antibody, may be
      effective in the treatment of patients with fibrillary glomerulonephritis. We
      describe 3 patients with fibrillary glomerulonephritis who were treated with
      rituximab for nephrotic-range proteinuria. Each patient also received standard
      antiproteinuria therapy, including blockade of the renin-angiotensin system and
      strict blood pressure control. All patients showed a decrease in proteinuria to
      less than 1.5 g/d of protein by 27 months, and kidney function was preserved
      throughout the duration of therapy and follow-up. No adverse effects were seen
      with rituximab. These outcomes suggest that treatment with rituximab may be a
      promising approach to the management of fibrillary glomerulonephritis, an entity
      previously considered refractory to therapy.

PMID- 18823686
TI  - Temporal trends in red blood transfusion among US dialysis patients, 1992-2005.
AB  - BACKGROUND: Studies addressing patterns and trends in red blood cell transfusion
      use in US hemodialysis patients surprisingly have received little attention in
      the last decade. STUDY DESIGN: Retrospective cohort study. SETTING &
      PARTICIPANTS: Point prevalent (as of January 1 of each calendar year 1992 to
      2005) dialysis patients with Medicare Part A and Part B as primary insurance (n =
      77,347 in 1992, n = 164,933 in 2005). The 6 months preceding January 1 of each
      year were used to assemble a comorbidity profile based on administrative claims
      data. PREDICTORS: Hemoglobin levels, patient characteristics, comorbid
      conditions. OUTCOMES: Blood transfusion events obtained from Part A and Part B
      files using code files for both whole and packed red blood cell transfusions and
      hemoglobin levels. MEASUREMENTS: Comorbid conditions were defined by the presence
      of 1 or more inpatient/outpatient institutional claims (inpatient
      hospitalization, skilled nursing facility, or home health agency), 2 or more
      outpatient or physician/supplier claims, or 1 or more outpatient and 1 or more
      physician/supplier claims for atherosclerotic heart disease, congestive heart
      failure, cerebrovascular accidents/transient ischemic attacks, peripheral
      vascular disease, other cardiovascular diseases, chronic obstructive pulmonary
      disease, gastrointestinal disorders, liver disease, arrhythmia, and diabetes
      mellitus. RESULTS: Raw transfusion rates decreased in both outpatient and
      inpatient settings from 535.33/1,000 patient-years for 1992 prevalent dialysis
      patients to 263.65/1,000 patient-years in 2005 (P for trend < 0.001, 1992 versus
      1999 and 1999 versus 2005). Adjusted rates decreased similarly. This phenomenon
      could not be explained by changes in case mix. LIMITATIONS: Cause, effect, and
      confounding cannot be separated in this observational study. The accuracy of
      blood transfusion billing data is unknown. Temporal trends may be related to
      factors other than erythropoiesis-stimulating agent use. CONCLUSION: Transfusion
      events in hemodialysis patients decreased more than 2-fold from 1992 to 2005;
      most of the decrease occurred in the first 5 years after erythropoietin was
      introduced.

PMID- 18823688
TI  - Scope and design of the Following Rehabilitation, Economics and Everyday-Dialysis
      Outcome Measurements (FREEDOM) Study.
AB  - BACKGROUND: Conventional thrice-weekly hemodialysis (HD) has limited the ability
      to generate further improvements in patient quality of life, morbidity, and
      mortality. Daily HD (DHD) offers the promise of providing clinical and economic
      benefits. The objectives of the Following Rehabilitation, Economics and Everyday
      Dialysis Outcome Measurements Study are to evaluate outcomes of DHD (6 times/wk)
      with the NxStage System One (NxStage Medical Inc, Lawrence, MA) device. DESIGN:
      Cohort study with matched control group. SETTING & PARTICIPANTS: The DHD group
      will include up to 500 participants at 70 clinical sites, enrolling for 3 years
      with a minimum of 1-year follow-up. Study candidates include adult patients (age
      >or= 18 years) with end-stage renal disease who are considered suitable
      candidates for DHD with the NxStage System One device by the treating physician
      and who have Medicare as their primary insurance payer. The control group will
      consist of a matched thrice-weekly in-center HD cohort derived from the US Renal
      Data System database using a 10:1 ratio, totaling 5,000 patients. PREDICTOR:
      Treatment with DHD and "standard of care" thrice-weekly HD. OUTCOMES &
      MEASUREMENTS: The primary intent-to-treat analysis compares hospitalization
      days/patient-year between the DHD and thrice-weekly HD groups. Other outcomes
      recorded in both groups include non-treatment-related medical expenditures. In
      addition, in the DHD cohort, changes in quality-of-life measures (baseline, 4 and
      12 months, and every 6 months thereafter); urea kinetics; parameters related to
      anemia, bone and mineral metabolism, and nutrition; vascular access
      interventions; and use of medications will be examined. CONCLUSIONS: This study
      has the potential to elucidate the health and economic benefits of DHD and
      complement results of current clinical trials.

PMID- 18823687
TI  - Effect of renin-angiotensin-aldosterone system inhibition, dietary sodium
      restriction, and/or diuretics on urinary kidney injury molecule 1 excretion in
      nondiabetic proteinuric kidney disease: a post hoc analysis of a randomized
      controlled trial.
AB  - BACKGROUND: Tubulointerstitial damage plays an important role in chronic kidney
      disease (CKD) with proteinuria. Urinary kidney injury molecule 1 (KIM-1) reflects
      tubular KIM-1 and is considered a sensitive biomarker for early tubular damage.
      We hypothesized that a decrease in proteinuria by using therapeutic interventions
      is associated with decreased urinary KIM-1 levels. STUDY DESIGN: Post hoc
      analysis of a randomized, double-blind, placebo-controlled, crossover trial.
      SETTING & PARTICIPANTS: 34 proteinuric patients without diabetes from our
      outpatient renal clinic. INTERVENTION: Stepwise 6-week interventions of losartan,
      sodium restriction (low-sodium [LS] diet), their combination, losartan plus
      hydrochlorothiazide (HCT), and the latter plus an LS diet. OUTCOMES &
      MEASUREMENTS: Urinary excretion of KIM-1, total protein, and N-acetyl-beta-d
      glucosaminidase (NAG) as a positive control for tubular injury. RESULTS: Mean
      baseline urine protein level was 3.8 +/- 0.4 (SE) g/d, and KIM-1 level was 1,706
      +/- 498 ng/d (increased compared with healthy controls; 74 ng/d). KIM-1 level was
      decreased by using placebo/LS (1,201 +/- 388 ng/d; P = 0.04), losartan/high
      sodium (1,184 +/- 296 ng/d; P = 0.09), losartan/LS (921 +/- 176 ng/d; P = 0.008),
      losartan/high sodium plus HCT (862 +/- 151 ng/d; P = 0.008) and losartan/LS plus
      HCT (743 +/- 170 ng/d; P = 0.001). The decrease in urinary KIM-1 levels
      paralleled the decrease in proteinuria (R = 0.523; P < 0.001), but not blood
      pressure or creatinine clearance. 16 patients reached target proteinuria with
      protein less than 1 g/d, whereas KIM-1 levels normalized in only 2 patients.
      Urinary NAG level was increased at baseline and significantly decreased during
      the treatment periods of combined losartan plus HCT only. The decrease in urinary
      NAG levels was not closely related to proteinuria. LIMITATIONS: Post hoc
      analysis. CONCLUSIONS: Urinary KIM-1 level was increased in patients with
      nondiabetic CKD with proteinuria and decreased in parallel with proteinuria by
      using losartan, sodium restriction, their combination, losartan plus HCT, and the
      latter plus sodium restriction. These results are consistent with the hypothesis
      of amelioration of proteinuria-induced tubular damage. Long-term studies are
      warranted to evaluate whether targeting treatment on KIM-1 can improve outcomes
      in patients with CKD with proteinuria.

PMID- 18823689
TI  - The effect of severe carotid occlusive disease and its surgical treatment on
      cognitive functions of the brain.
AB  - Surgery of a high-grade carotid stenosis is evidence-based stroke prevention.
      Also cognitive effects are reported after carotid endarterectomy (CEA): both
      deterioration and improvement, the former attributed to perioperative
      complications and the latter often to learning effect. By imaging, brain
      perfusion and diffusion changes were shown in subjects with a high-grade stenosis
      undergoing CEA. We wanted to find out if the cognition of patients undergoing CEA
      display postoperative worsening or true improvement in association with findings
      in serial MR imaging. The patients had a poorer overall cognition than healthy
      matched controls. The cerebral hemisphere ipsilateral to the stenosis had higher
      diffusion and more sluggish perfusion leading to perfusion deficits. These
      asymmetries were abolished by CEA. Postoperatively, the patients showed a trend
      for cognitive worsening, most often attentional, but over months, the group
      performance improved similarly to the controls. Still, lower baseline perfusion
      was associated with a greater cognitive improvement, most clearly in executive
      functions. Consequently, despite the risk for transient decline, true cognitive
      benefit by CEA seems possible.

PMID- 18823690
TI  - Malignant transformation of mature cystic teratoma of the ovary: experience at a
      single institution.
AB  - OBJECTIVES: Malignant transformation of mature cystic teratoma (MCT) of ovary is
      very rare. Therefore, the clinicopathologic characteristics, treatment and
      prognostic factors are not yet well established. The aim of this study was to
      review our experience with this malignancy and previously published reports in
      the literature. STUDY DESIGN: A review of pathologic reports for 2019 patients
      with ovarian MCT and 937 patients with primary ovarian cancer who were treated at
      the Asan Medical Center, Korea, from 1989 to 2007 identified 16 patients with
      malignant transformation from MCT. A retrospective chart review of these patients
      and a review of the literature were performed. RESULTS: The incidence rate of
      malignant transformation was 0.8% of all ovarian MCT. It accounted for 1.7% of
      all primary ovarian cancer. Squamous cell carcinoma was the most common
      histologic type, comprising 75%. The median age of the 16 patients was 50 years
      (range, 29-75 years). Mean tumor size was 14.5 cm (range, 5-26 cm). Twelve
      patients had some solid portions in the cyst containing fat fluid, hair, and/or
      calcification. According to the review of the patients in our study and of the
      literature, early detection and complete surgical resection are important for
      long-term survival. It seems that adjuvant chemotherapy or concurrent
      chemoradiation therapy have roles in treating this malignancy. CONCLUSIONS: Early
      detection is important for long-term survival. Old age, large tumor size, and
      solid portion in mature cystic teratoma seem to predict the malignant
      transformation of mature cystic teratoma.

PMID- 18823691
TI  - On the relation between native geometry and conformational plasticity.
AB  - In protein folding the term plasticity refers to the number of alternative
      folding pathways encountered in response to free energy perturbations such as
      those induced by mutation. Here we explore the relation between folding
      plasticity and a gross, generic feature of the native geometry, namely, the
      relative number of local and non-local native contacts. The results from our
      study, which is based on Monte Carlo simulations of simple lattice proteins, show
      that folding to a structure that is rich in local contacts is considerably more
      plastic than folding to a native geometry characterized by having a very large
      number of long-range contacts (i.e., contacts between amino acids that are
      separated by more than 12 units of backbone distance). The smaller folding
      plasticity of native geometries is probably a direct consequence of their higher
      folding cooperativity that renders the folding reaction more robust against
      single- and multiple-point mutations.

PMID- 18823693
TI  - Early versus delayed endocrine treatment of T2-T3 pN1-3 M0 prostate cancer
      without local treatment of the primary tumour: final results of European
      Organisation for the Research and Treatment of Cancer protocol 30846 after 13
      years of follow-up (a randomised controlled trial).
AB  - BACKGROUND: The timing of endocrine treatment (ET) for prostate cancer (PCa)
      remains controversial. The issue is addressed in European Organisation for the
      Research and Treatment of Cancer (EORTC) protocol 30846 for patients with lymph
      node-positive (pN1-3) cancer without local treatment of the primary tumour.
      OBJECTIVE: To evaluate the effect of early versus delayed treatment in pN1-3 PCa.
      DESIGN, SETTING, AND PARTICIPANTS: Two hundred thirty-four patients with
      histologically proven PCa and nodal metastases (pN1-3) were randomized to
      immediate versus delayed ET without treatment of the primary tumour. ET consisted
      of a depot luteinising hormone-releasing hormone (LHRH) agonist and 1 mo of an
      anti-androgen or surgical castration. The trial's main objective was to show non
      inferiority of delayed ET to immediate ET by ruling out a hazard ratio (HR) of
      1.50 for overall survival (OS), with 85% power at one-sided alpha=5%.
      MEASUREMENTS: All but three patients were treated as randomized. The median
      follow-up is 13 yr. The median protocol treatment duration was 2.7 yr in the
      delayed and 3.2 yr in the immediate ET groups. RESULTS AND LIMITATIONS: Overall,
      193 patients (82.5%) have died (97 on delayed ET and 96 on immediate ET), 59.4%
      of them as a result of PCa. The intention-to-treat analysis shows a 22% increase
      in the hazard of death of those randomized to delayed treatment (HR=1.22, 95%
      confidence interval [CI]: 0.92, 1.62). The difference is not statistically
      significant, but non-inferiority is also not proved. The median OS on immediate
      ET is 7.6 yr (95% CI, 6.3-8.3 yr) versus 6.1 yr (95% CI, 5.7-7.3 yr) in the
      delayed ET group. The 10-yr cumulative incidence of death resulting from PCa was
      55.6% in the delayed ET group versus 52.1% with immediate ET group. Similar
      conclusions hold for PCa-specific survival. CONCLUSIONS: After 13 years of follow
      up, survival or PCa-specific survival between immediate and delayed ET appear
      similar, but the trial is underpowered to reach its goal of showing non
      inferiority.

PMID- 18823695
TI  - Re: Annette Kuhn, Caroline Eggeman, Fiona Burkhard and Michael D. Mueller.
      Correction of erosion after suburethral sling insertion for stress incontinence:
      results and related sexual function. Eur Urol 2009;56:371-7.

PMID- 18823696
TI  - Editorial comment on: Recommendations on the use of botulinum toxin in the
      treatment of lower urinary tract disorders and pelvic floor dysfunctions: a
      European consensus report.

PMID- 18823697
TI  - Recommendations on the use of botulinum toxin in the treatment of lower urinary
      tract disorders and pelvic floor dysfunctions: a European consensus report.
AB  - CONTEXT: The increasing body of evidence and number of potential indications for
      the use of botulinum neurotoxins (BoNTs) in the lower urinary tract (LUT)
      underlines the pressing need for evidence-based guidelines. OBJECTIVE: A European
      expert panel consensus conference was convened with the main aim of evaluating
      the evidence and clinical considerations for the use of BoNTs in the treatment of
      urologic and pelvic-floor disorders and to propose relevant recommendations.
      EVIDENCE ACQUISITION: The quality of evidence from fully published English
      language literature in the PubMed and EMBASE databases was assessed using the
      European Association of Urology (EAU) levels of evidence (LoE). Recommendations
      were graded and approved by a unanimous consensus of the panel. EVIDENCE
      SYNTHESIS: The use of botulinum neurotoxin type A (BoNTA) is recommended in the
      treatment of intractable symptoms of neurogenic detrusor overactivity (NDO) or
      idiopathic detrusor overactivity (IDO) in adults (grade A). Caution is
      recommended in IDO because the risk of voiding difficulty and duration of effect
      have not yet been accurately evaluated. Repeated treatment can be recommended in
      NDO (grade B). The depth and location for bladder injections should be within the
      detrusor muscle outside the trigone (grade C). Dosage in children should be
      determined by body weight, with caution regarding total dose if also being used
      for treatment of spasticity, and minimum age (grade B). Existing evidence is
      inconclusive for recommendations in neurogenic detrusor-sphincter dyssynergia,
      bladder pain syndrome, prostate diseases, and pelvic-floor disorders. The use of
      BoNTA in the LUT with the current dosages and techniques is considered to be safe
      overall (grade A). CONCLUSIONS: The consensus committee recommends larger placebo
      controlled and comparative trials to evaluate the efficacy of single and repeat
      injections, the duration of effect, the optimal dosage and injection technique,
      the timing for repeat injection, and the short- and long-term safety of the
      treatment in LUT and pelvic-floor disorders.

PMID- 18823698
TI  - Re: Herve Baumert, Mehrak Hekmati, Irene Dunia, et al. Laparoscopy in ureteral
      engineering: a feasibility study. Eur Urol 2008;54:1154-63.

PMID- 18823699
TI  - EMP3 as a tumor suppressor gene for esophageal squamous cell carcinoma.
AB  - EMP3, epithelial membrane protein 3, was recently reported to be a tumor
      suppressor gene in neuroblastomas and gliomas. We found that EMP3 was commonly
      repressed in esophageal squamous cell carcinoma (ESCC) cell lines by
      oligonucleotide microarrays. Its overexpression in ESCC cell lines caused growth
      inhibition with morphological changes and TERT repression. In addition to
      promoter hypermethylation, TSA caused repression of EMP3, indicating the
      involvement of histone deacetylase-regulated repressors. The post-recurrent
      survival after radical surgery was poorer in ESCC patients with lower EMP3
      expression. We propose that EMP3 may be a tumor suppressor gene at the late step
      of ESCC carcinogenesis.

PMID- 18823700
TI  - Variability of origin for the neocentromeric sequences in analphoid supernumerary
      marker chromosomes of well-differentiated liposarcomas.
AB  - Well-differentiated liposarcomas (WDLPS) and dedifferentiated liposarcomas are
      cytogenetically characterized by the presence of supernumerary ring or giant
      chromosomes containing amplified material from the 12q14-15 region. These
      chromosomes contain neocentromeres, which are able to bind the kinetochore
      proteins and to ensure a stable mitotic transmission although they do not show
      detectable alpha-satellite sequences. WDLPS is the sole solid tumor for which the
      presence of a neocentromere is a consistent and specific feature. By
      immunostaining with anti-centromere antibodies in combination with FISH analysis
      (immunoFISH) in four cases of WDLPS, we have shown that sequences from the region
      12q14-21 region were not located at the neocentromere site. In addition, we have
      microdissected the neocentromeric region from a giant supernumerary chromosome in
      the 94T778 WDLPS cell line. By using immunoFISH and positional cloning we have
      shown that the neocentromere of this cell line originated from a region at
      4p16.1, rich in AT sequences and in long interspersed nucleotide element (LINE)1,
      that was co-amplified with 12q14-15. We have observed that this 4p sequence was
      not involved in the neocentromere of the supernumerary giant chromosome present
      in the 93T449 WDLPS cell line derived from a metachronous recurrence of the same
      primary WDLPS than 94T778. Altogether, these results indicate that the
      neocentromeres in WDLPS originate from amplified chromosomal regions other than
      12q14-15 and do not involve a specific and recurrent DNA sequence. These
      sequences might be activated for centromeric function by epigenetic mechanisms.

PMID- 18823701
TI  - CASP8 D302H and meningioma risk: an analysis of five case-control series.
AB  - Caspase 8 (CASP8) is a key regulator of apoptosis or programmed cell death, and
      hence a defence against cancer. The CASP8 polymorphism D302H has recently been
      shown to influence the risk of breast cancer. We tested the hypothesis that the
      CASP8 polymorphism D302H may influence risk of meningioma through analysis of
      five independent series of case patients and controls (n=631 and 637,
      respectively). Carrier status for 302H was not associated with a statistically
      significantly increased risk (OR=1.16; 95% CI: 0.87-1.53; P=0.31) making it
      unlikely that this variant contributes to the inherited risk of meningioma.

PMID- 18823702
TI  - Sorption behavior of heavy metal species by soakaway sediment receiving urban
      road runoff from residential and heavily trafficked areas.
AB  - Groundwater contamination by heavy metals from infiltration facilities receiving
      road runoff is of potential concern. In this study, sorption tests were conducted
      to evaluate the influence of the water quality of road runoff, especially
      dissolved organic matter (DOM), on the sorption of heavy metal species by
      soakaway sediment. Sequential batch tests were conducted to assess metal sorption
      by the soakaway sediment receiving road runoff from residential and heavily
      trafficked areas. Ni was adsorbed by the sediment, indicating that soakaway
      sediments function to prevent groundwater contamination by Ni. In contrast, Zn
      was released from the soakaway sediment in sorption tests using heavily
      trafficked road dust leachates. Ni, Cu, Zn, and dissolved organic carbon
      concentrations were higher in soakaway sediment leachates obtained by sorption
      tests using heavily trafficked road dust leachates than those using residential
      road dust leachates, suggesting traffic activities contaminate these pollutants.
      A large portion of Zn, released from the soakaway sediment, existed as stable
      complexes. DOM in road runoff possibly enhances the release of Zn from the
      sediments within infiltration facilities and might cause groundwater
      contamination.

PMID- 18823703
TI  - Approaches for the treatment of waste streams of the aluminium anodising
      industry.
AB  - The aluminium anodising industry is an important industrial sector that
      invariably generates great amounts of different waste streams. Classical and
      especially new-developing technologies dealing with them are reviewed. Innovative
      methods are mainly based on engineering geochemical processes, looking for the
      recovery of resource materials and the reduction of emissions to the environment.
      These represent a promising alternative to the classical method (neutralisation
      process and anodising mud disposal) which is an end-of-pipe solution. Among the
      treatments recently proposed, there are the use of anodising mud in the
      manufacture of refractory bodies, and the synthesis of useful minerals from the
      wastewaters arising from the etching, anodising and brightening processes. The
      viability of the application of such methods in the treatment of waste streams of
      the aluminium anodising industry is discussed, pointing out the main shortcomings
      and benefits of each of them. For those methods appearing environmentally
      friendly the process cost and the actual marketability of the final products
      should be determinant on their near future applicability.

PMID- 18823704
TI  - Catalytic dechlorination of polychlorinated biphenyls in soil by palladium-iron
      bimetallic catalyst.
AB  - Pd/Fe bimetallic particles were synthesized by chemical deposition and used to
      dechlorinate 2,2',4,5,5'-pentachlorobiphenyl in soil. Batch experiments
      demonstrated that the Pd/Fe bimetallic particles could effectively dechlorinate
      2,2',4,5,5'-pentachlorobiphenyl. Dechlorination was affected by several factors
      such as reaction time, Pd loading, the amount of Pd/Fe used, initial soil pH, and
      2,2',4,5,5'-pentachlorobiphenyl concentration. The results showed that higher Pd
      loading, higher dosage of Pd/Fe, lower initial concentration of 2,2',4,5,5'
      pentachlorobiphenyl and slightly acid condition were beneficial to the catalytic
      dechlorination of 2,2',4,5,5'-pentachlorobiphenyl. The degradation of 2,2',4,5,5'
      pentachlorobiphenyl, catalyzed by Pd/Fe followed pseudo-first-order kinetics.

PMID- 18823705
TI  - Equilibrium studies on hydrolysis of urea in a semi-batch reactor for production
      of ammonia to reduce hazardous pollutants from flue gases.
AB  - The increasing environmental awareness and the mandate of the pollution control
      agencies in various part of country for lowering emission of air pollutants such
      as CO(2), NO(x), SO(2) and fly ash emissions, has increased the urgency for
      reviewing options and alternatives to accomplish the above objective. The
      addition of ammonia into the flue gas stream as a conditioning agent is found to
      be used in recent years for the reduction of air pollutants. Flue gas
      conditioning requires in situ generation of ammonia as the transportation and
      storage of anhydrous ammonia is hazardous in nature. The equilibrium study on
      hydrolysis of urea was done in a semi-batch glass reactor to investigate the
      effect of reaction temperature, initial feed concentration and stirring speed on
      ammonia production. Few experiments were carried out in a semi-batch reactor at
      atmospheric pressure by using different concentration of urea solution from 10 to
      40 wt% of urea to water and equilibrium study has been done. The study reveals
      that conversion increases exponentially with an increase in temperature but the
      conversion decreases with increase in the inlet feed concentration of urea
      solution. Furthermore, the effect of stirring speed on conversion has also been
      studied and it found that conversion increases with increase in stirring speed.

PMID- 18823706
TI  - Characterization and activity of Pd-modified TiO2 catalysts for photocatalytic
      oxidation of NO in gas phase.
AB  - Pd-modified TiO(2) prepared by thermal impregnation method was used in this study
      for photocatalytic oxidation of NO in gas phase. The physico-chemical properties
      of Pd/TiO(2) catalysts were characterized by X-ray diffraction analysis (XRD),
      Brunauer-Emmett-Teller measurements (BET), X-ray photoelectron spectrum analysis
      (XPS), transmission electron microscopy (TEM), high resolution-transmission
      electron microscopy (HR-TEM), UV-vis diffuse reflectance spectra (UV-vis DRS) and
      photoluminescence spectra (PL). It was found that Pd dopant existed as PdO
      particles in as-prepared photocatalysts. The results of PL spectra indicated that
      the photogenerated electrons and holes were efficiently separated after Pd
      doping. During in situ XPS study, it was found that the content of hydroxyl
      groups on the surface of Pd/TiO(2) increased when the catalyst was irradiated by
      UV light, which could result in the improvement of photocatalytic activity. The
      activity test showed that the optimum Pd dopant content was 0.05 wt.%. And the
      maximum conversion of NO was about 72% higher than that of P25 when the initial
      concentration of NO was 200 ppm, which showed that Pd/TiO(2) photocatalysts could
      be potentially applied to oxidize higher concentration of NO.

PMID- 18823707
TI  - Something about Mary.

PMID- 18823708
TI  - PVN electrical stimulation prolongs withdrawal latencies and releases oxytocin in
      cerebrospinal fluid, plasma, and spinal cord tissue in intact and neuropathic
      rats.
AB  - We are studying an endogenous, oxytocinergic analgesia system to obtain more
      information about normal and pathological pain processes. In the recent years,
      this oxytocinergic system has been shown to be involved in normal and
      pathological pain suppression. The paraventricular nucleus (PVN) of the
      hypothalamus is an important source of brain oxytocin (OT). A descending pathway
      reaching the dorsal horn in the spinal cord was postulated to mediate analgesic
      effects at the spinal cord level. However, the oxytocin concentration during pain
      conditions and during PVN electrical stimulation needs to be determined. We
      designed experiments to measure the OT concentration in cerebrospinal fluid
      (CSF), plasma, and OT protein in lumbar spinal cord tissue in control and
      neuropathic rats. Sciatic loose ligature was used as the experimental method to
      produce neuropathic pain. The main findings were (1) Chronic pain experiments in
      animals showed that the stimulation of the anterior part of the PVN increased OT
      concentration and produced analgesia states, as measured by von Frey, cold, and
      heat plantar tests. (2) Differential effects were produced by electrical
      stimulation of the anterior or posterior regions of the PVN; electrical
      stimulation of the anterior part of the PVN enhanced the OT concentration in CSF
      and plasma, and it also increased OT protein concentrations in the spinal cord
      tissue; in contrast, the stimulation of the posterior part of the PVN only
      increased OT concentrations in CSF. These results suggest the participation of an
      endogenous analgesia system mediated by OT.

PMID- 18823709
TI  - Comment on article by Eligio-Garcia et al. entitled "Frequency of Giardia
      intestinalis assemblages isolated from dogs and humans in a community from
      Culiacan, Sinaloa, Mexico using beta-giardin restriction gene".

PMID- 18823710
TI  - Comparative evaluation of enzyme-linked immunosorbent assay based on crude and
      purified antigen in the diagnosis of canine visceral leishmaniasis in symptomatic
      and oligosymptomatic dogs.
AB  - This study evaluated the performance of crude total antigen (CTA) and fucose
      mannose ligand antigen (FML) in an enzyme-linked immunosorbent assay for
      diagnosis of canine visceral leishmaniasis (CVL). The assays used sera from known
      negative controls (n=30), clinically symptomatic (n=30) and oligosymptomatic
      (n=30) parasitologically proven infection (by microscopy). Aspirates of popliteal
      lymph node from infected canines were colleted to score parasitism and compared
      with the ELISA results. The study indicated that FML used in ELISA provided high
      sensitivity for detecting oligosymptomatic dogs (90%) and CTA showed greater
      sensitivity than FML for symptomatic canines (90%). In oligosymptomatic dogs,
      specificity was 100% for CTA-ELISA, but in symptomatic dogs, FML specificity was
      higher (96.7%) than CTA-ELISA (93.3%). A significant correlation was observed
      between the degree of parasitism and the results obtained in CTA-ELISA. Since no
      available antigen offers 100% specificity and sensitivity for CVL diagnosis, the
      choice of antigen used must depend on the aim of the investigation.

PMID- 18823711
TI  - Detection of Leishmania infantum in captive wolves from Southwestern Europe.
AB  - The aim of the present study was to determine the prevalence of Leishmania
      infantum infection in a wild reservoir host (Canis lupus) throughout an endemic
      area for the disease (Southern Europe). For that reason, the serum and peripheral
      blood samples of 33 captive wolves from the European Breeding of Endangered
      Species Programme (EEP) were analyzed using the enzyme-linked immunosorbent assay
      (ELISA) and real-time quantitative PCR (qPCR). L. infantum was detected in three
      samples from Central Portugal and Central and Northern Spain. Even though L.
      infantum infection in positive samples was low, surveillance of zoonotic
      leishmaniosis in this population is recommended as the parasite load could be
      higher in other tissues due to parasite tropism and most of the EEP institutions
      studied are located in endemic areas for canine leishmaniosis in Europe.

PMID- 18823712
TI  - On objectives and achievements of the journal medical hypotheses and the utopia
      of following-up 'true positives'.

PMID- 18823713
TI  - Sequential comparison of seed loss and prostate dosimetry of stranded seeds with
      loose seeds in 125I permanent implant for low-risk prostate cancer.
AB  - PURPOSE: To compare stranded seeds (SSs) with loose seeds (LSs) in terms of
      prostate edema, dosimetry, and seed loss after (125)I brachytherapy. METHODS AND
      MATERIALS: Two prospective cohorts of 20 men participated in an institutional
      review board-approved protocols to study postimplant prostate edema and its
      effect on dosimetry. The LS cohort underwent brachytherapy between September 2002
      and July 2003 and the SS cohort between April 2006 and January 2007. Both cohorts
      were evaluated sequentially using computed tomography-magnetic resonance imaging
      fusion-based dosimetry on Days 0, 7, and 30. No hormonal therapy or supplemental
      beam radiotherapy was used. RESULTS: Prostate edema was less in the SS cohort at
      all points (p = NS). On Day 0, all the prostate dosimetric factors were greater
      in the LS group than in the SS group (p = 0.003). However, by Days 7 and 30, the
      dosimetry was similar between the two cohorts. No seeds migrated to the lung in
      the SS cohort compared with a total of five seeds in 4 patients in the LS cohort.
      However, the overall seed loss was greater in the SS cohort (24 seeds in 6
      patients; 1.1% of total vs. 0.6% for LSs), with most seeds lost through urine (22
      seeds in 5 patients). CONCLUSION: Despite elimination of venous seed migration,
      greater seed loss was observed with SSs compared with LSs, with the primary site
      of loss being the urinary tract. Modification of the technique might be necessary
      to minimize this. Prostate dosimetry on Days 7 and 30 was similar between the SS
      and LS cohorts.

PMID- 18823714
TI  - Postmastectomy chest wall radiation to a temporary tissue expander or permanent
      breast implant--is there a difference in complication rates?
AB  - PURPOSE: The purpose of this study was to evaluate the likelihood of
      complications and cosmetic results among breast cancer patients who underwent
      modified radical mastectomy (MRM) and breast reconstruction followed by radiation
      therapy (RT) to either a temporary tissue expander (TTE) or permanent breast
      implant (PI). METHODS AND MATERIALS: Records were reviewed of 74 patients with
      breast cancer who underwent MRM followed by breast reconstruction and RT.
      Reconstruction consisted of a TTE usually followed by exchange to a PI. RT was
      delivered to the TTE in 62 patients and to the PI in 12 patients. Dose to the
      reconstructed chest wall was 50 Gy. Median follow-up was 48 months. The primary
      end point was the incidence of complications involving the reconstruction.
      RESULTS: There was no significant difference in the rate of major complications
      in the PI group (0%) vs. 4.8% in the TTE group. No patients lost the
      reconstruction in the PI group. Three patients lost the reconstruction in the TTE
      group. There were excellent/good cosmetic scores in 90% of the TTE group and 80%
      of the PI group (p = 0.22). On multivariate regression models, the type of
      reconstruction irradiated had no statistically significant impact on complication
      rates. CONCLUSIONS: Patients treated with breast reconstruction and RT can
      experience low rates of major complications. We demonstrate no significant
      difference in the overall rate of major or minor complications between the TTE
      and PI groups. Postmastectomy RT to either the TTE or the PI should be considered
      as acceptable treatment options in all eligible patients.

PMID- 18823715
TI  - Radiotherapeutic parameters predictive of liver complications induced by liver
      tumor radiotherapy.
AB  - PURPOSE: The purpose of this study was to identify radiotherapeutic parameters
      for predicting the occurrence of liver complications induced by radiotherapy of a
      liver tumor. METHODS AND MATERIALS: From 2001 to 2003, a total of 131 patients
      with hepatocellular carcinoma received three-dimensional conformal radiotherapy.
      The total dose was determined by the fraction of nontumor liver receiving 50% of
      the isocenter dose (V(50%)). We evaluated three sets of published radiation dose
      guidelines using nontumor liver volume or a combination of nontumor liver volume
      and hepatic functional reserve. The V(50%) was divided into three intervals
      (<33%, 33-66%, and >66%) and four categories (<25%, 25-49%, 50-75%, and >75%)
      according to guidelines by the University of Michigan and the Yonsei University,
      respectively. According to the guideline of Cheng et al., the radiation dose was
      determined by the indocyanin green retention rate at 15 min (ICG-R15) and the
      nontumor liver volume. RESULTS: Of the 131 patients, 13 patients (9.9%) presented
      with liver complications. The incidence was 11.1%, 10.3%, and 18.2%,
      respectively, for a V(50%) of less than 33%, 33% to 66%, and more than 66%. The
      observed hepatic toxicity incidence was 10%, 12.1%, and 10.4% respectively for a
      V(50%) of less than 25%, 25% to 49%, and 50% to 75%, respectively. Nontumor liver
      volume and ICG-R15 were not predictors of liver complications. The incidence of
      liver complications was significantly increased in patients with Child-Pugh Class
      B (p = 0.044). CONCLUSIONS: The parameter, V(50%), can be divided into 4
      categories and used to predict acceptable toxicity. Furthermore, indicators of
      liver functional status like the Child-Pugh class may be more important and
      useful parameters than ICG-R15 for predicting radiation-related liver disease.

PMID- 18823716
TI  - Health-related quality of life in cervical cancer survivors: a population-based
      survey.
AB  - PURPOSE: In a population-based sample of cervical cancer survivors, health
      related quality of life (HRQoL) was assessed 2-10 years postdiagnosis. METHODS
      AND MATERIALS: All patients given a diagnosis of cervical cancer in 1995-2003 in
      the Eindhoven region, The Netherlands, and alive after Jan 2006 were identified
      through the cancer registry. Generic HRQoL (36-Item Short-Form Health Survey, EQ
      5D), cervical cancer-specific HRQoL (European Organization for Research and
      Treatment of Cancer Quality-of-Life questionnaire cervical cancer module), and
      anxiety (6-item State Trait Anxiety Inventory) were assessed and compared with a
      reference population (n = 349). Data for tumor characteristics at diagnosis and
      disease progression were available. RESULTS: A total of 291 women responded
      (69%), with a mean age of 53 +/- 13 (SD) years (range, 31-88 years). Treatment
      had consisted of surgery (n = 195) or a combination of therapies (n = 75); one
      woman had not been treated. Of all women, 85% were clinically disease free, 2%
      had a recurrence/metastasis, and in 13%, this was unknown. After controlling for
      background characteristics (age, education, job and marital status, having
      children, and country of birth), generic HRQoL scale scores were similar to the
      reference population, except for worse mental health in survivors. The most
      frequent symptoms were crampy pain in the abdomen or belly (17%), urinary leakage
      (15%), menopausal symptoms (18%), and problems with sexual activity. Compared
      with the 6-10-year survivors, more sexual worry and worse body image were
      reported by the 2-5-year survivors. Compared with surgery only, especially
      primary radiotherapy was associated with an increased frequency of treatment
      related side effects, also after controlling for age and disease stage at
      diagnosis and follow-up. CONCLUSIONS: Most cervical cancer survivors were coping
      well, although their mental health was worse than in the reference population.
      Even after 2-10 years, radiotherapy was associated with an increased frequency of
      treatment-related side effects.

PMID- 18823717
TI  - Retrospective analysis of artifacts in four-dimensional CT images of 50 abdominal
      and thoracic radiotherapy patients.
AB  - PURPOSE: To quantify the type, frequency, and magnitude of artifacts in four
      dimensional (4D) CT images acquired using a multislice cine method. METHODS AND
      MATERIALS: Fifty consecutive patients who underwent 4D-CT scanning and
      radiotherapy for thoracic or abdominal cancers were included in this study. All
      the 4D-CT scans were performed on the GE multislice PET/CT scanner with the
      Varian Real-time Position Management system in cine mode. The GE Advantage 4D
      software was used to create 4D-CT data sets. The artifacts were then visually and
      quantitatively analyzed. We performed statistical analyses to evaluate the
      relationships between patient- or breathing-pattern-related parameters and the
      occurrence as well as magnitude of artifacts. RESULTS: It was found that 45 of 50
      patients (90%) had at least one artifact (other than blurring) with a mean
      magnitude of 11.6 mm (range, 4.4-56.0 mm) in the diaphragm or heart. We also
      observed at least one artifact in 6 of 20 lung or mediastinal tumors (30%).
      Statistical analysis revealed that there were significant differences between
      several breathing-pattern-related parameters, including abdominal displacement (p
      < 0.01), for the subgroups of patients with and without artifacts. The magnitude
      of an artifact was found to be significantly but weakly correlated with the
      abdominal displacement difference between two adjacent couch positions (R = 0.34,
      p < 0.01). CONCLUSIONS: This study has identified that the frequency and
      magnitude of artifacts in 4D-CT is alarmingly high. Significant improvement is
      needed in 4D-CT imaging.

PMID- 18823718
TI  - [Water-electrolyte abnormalities during pregnancy: maternal and fetal
      complications (about a case)].
AB  - Water-electrolyte abnormalities while pregnancy or for infant are very serious.
      We present a case of a woman at 26 weeks who had gestation pernicious vomiting
      that led to major extracellular dehydration, water intoxication and acute renal
      insufficiency. The etiology was a volvulus on common mesentery. Hyperemesis
      disappeared thanks to surgical treatment. The mother and her fetus would later
      present serious complications due to the water-electrolyte imbalance correction.
      The fetus suffered from cerebral hemorrhage and subdural hematoma subordinate to
      brain edema resorption. The mother presented centropontine myelinolysis. The
      treatment of electrolyte abnormalities during pregnancy could lead to serious
      complications for the mother and fatal for the foetus.

PMID- 18823719
TI  - Transfusion-related acute lung injury (TRALI) during remission induction course
      of acute myeloid leukemia: a possible role for all-transretinoic-acid (ATRA)?
AB  - Transfusion-related acute lung injury (TRALI) is a clinical syndrome
      characterized by sudden onset of respiratory distress due to pulmonary edema
      during or following transfusion. Two proposed pathophysiologic mechanisms for
      TRALI were proposed: the antibody hypothesis and the two-event hypothesis. The
      two-event hypothesis postulates that a pathway to neutrophil activation and
      aggregation can occur without leukocyte antibodies. We report a case of TRALI
      occurring during remission induction course of acute myeloid leukemia in a 27
      year-old woman who received All-transretinoic-acid (ATRA). We postulate that ATRA
      may have played a role in this life-threatening complication by priming
      neutrophil and enhancing their adherence and their activation in the pulmonary
      endothelium. TRALI improved with non-invasive ventilation support and use of high
      dose corticosteroids.

PMID- 18823720
TI  - WITHDRAWN: Effect of TCF7L2 polymorphism on the genetic susceptibility to obesity
      in the Tunisian population.
AB  - Cet article a du etre retire conformement a la ligne de conduite d'Elsevier
      concernant le retrait d'articles. Vous pouvez consulter le site
      (http://www.elsevier.com/locate/withdrawalpolicy) pour de plus amples
      renseignements. L'editeur vous prie d'accepter ses excuses pour ce desagrement.

PMID- 18823721
TI  - Neurobiological substrates of cue-elicited craving and anhedonia in recently
      abstinent opioid-dependent males.
AB  - AIM: Drug-related stimuli may induce craving in addicted patients, prompting drug
      seeking behaviour. In addition, studies have shown addicted patients to be less
      sensitive to pleasant, but non-drug-related, stimuli; a condition generally
      referred to as anhedonia. The neural correlates of cue-induced craving and
      anhedonia in opioid-dependent patients are, however, not well understood. We
      studied brain activation patterns following visual presentation of neutral,
      pleasant and heroin-related cues. METHODS: Detoxified opioid-dependent males
      (n=12) and healthy male control subjects (n=17) underwent functional magnetic
      resonance imaging (fMRI) while subjects viewed neutral, pleasant and heroin
      related images. In addition, subjective cue-elicited craving (OCDUS and DDQ) and
      anhedonia (SHAPS) were measured. RESULTS: Opioid-dependent subjects, but not
      control subjects, showed significant increases in activation in hippocampal
      region and subcortical limbic structures in response to heroin-related stimuli
      with a significant group x stimulus interaction effect for the subthalamic
      nucleus (STN). Control subjects, but not opioid-dependent subjects, showed
      significant increases in activation of anterior frontal areas and basal ganglia
      while viewing pleasant images with a significant group x stimulus interaction
      effect for bilateral anterior prefrontal cortex. Regression analyses showed a
      positive association between cue-elicited craving and ventral tegmental area
      (VTA) activation in response to heroin-related stimuli in heroin-dependent
      patients. In addition, a negative correlation was found between self-reported
      anhedonia and medial prefrontal regions in both groups. CONCLUSIONS: Our findings
      suggest that the VTA is prominently involved in cue-induced opioid craving for
      heroin stimuli, in addition to mesolimbic and mesocortical pathways as identified
      in previous research. The present study also provides further evidence for the
      involvement of the STN in reward processing. Finally, our data support the
      presence of reduced brain activation in heroin-dependent patients in response to
      pleasant (non-drug-related) stimuli.

PMID- 18823722
TI  - Salmonella Indiana as a cause of abortion in ewes: Genetic diversity and
      resistance patterns.
AB  - Salmonella enterica subspecies enterica Indiana, a food-borne serovar uncommon in
      most countries, was responsible for an outbreak of abortion in a flock of Lacaune
      dairy ewes in southern Spain. Drinking water and feedstuff samples were analysed
      in an attempt to determine the source of the infection. Pigeons (Columba livia)
      and turtledoves (Streptopelia turtur) in close contact with the ewes were
      captured and examined for the bacterium. Seventeen S. Indiana strains were
      isolated from the ewes and wild birds and the genetic similarity among them
      analysed by Pulsed Field Gel Electrophoresis (PFGE) after the digestion of their
      genomic DNA with the restriction enzyme XbaI. The results suggest the wild birds
      might be responsible for the outbreak in the ewes. The strains recovered were
      fully susceptible to 15 out of the 16 antimicrobial agents tested: ampicillin,
      amoxycillin clavulanate, cephalothin, ceftriaxone, gentamicin, neomycin,
      streptomycin, tetracycline, ciprofloxacin, enrofloxacin, sulphonamides,
      trimethoprim-sulphamethoxazole, apramycin, colistin and chloramphenicol.
      Differences in the resistance pattern to nalidixic acid were observed; 11 strains
      (64.7%) were nalidixic acid resistant (R-Nx) and 6 (35.3%) sensitive (S-Nx).
      Among the R-Nx strains, a substitution of Gly to Cys at position 81 (Gly81aCys)
      of the gyrA gene in 10 strains isolated from wild birds and ovine foetuses, and
      of Asp to Tyr at position 87 (Asp87aTyr) in one strain isolated from ewe faeces,
      were revealed by sequencing the gene. To control the outbreak, enrofloxacin
      treatment was administered for 5 days. The same therapy was used to prevent
      infection during following gestation cycles, administering the antimicrobial
      agent at presentation and over 4 weeks before birth. Anti-bird meshes and closed
      drinking and feeding troughs were also installed to prevent further contact of
      the ewes with wild birds.

PMID- 18823723
TI  - In vitro antimicrobial activity against 10 North American and European Lawsonia
      intracellularis isolates.
AB  - The objective of this study was to determine the in vitro minimum inhibitory
      concentration (MIC) of antimicrobials against 10 isolates of Lawsonia
      intracellularis, the etiological agent of proliferative enteropathy (PE).
      Antimicrobials tested included carbadox, chlortetracycline, lincomycin, tiamulin,
      tylosin and valnemulin. The MIC of each antimicrobial against L. intracellularis
      was determined using a tissue culture system and was identified as the lowest
      concentration that inhibited 99% of L. intracellularis growth, as compared to the
      antimicrobial-free control. Each antimicrobial concentration was evaluated for
      both intracellular and extracellular activity against L. intracellularis, an
      obligately intracellular bacterium. When tested for intracellular activity,
      carbadox, tiamulin, and valnemulin were the most active antimicrobials with MICs
      of < or =0.5microg/ml. Tylosin (MICs ranging from 0.25 to 32microg/ml) and
      chlortetracycline (MICs ranging from 0.125 to 64microg/ml) showed intermediate
      activities and lincomycin (MICs ranging from 8 to >128mIcog/ml) showed the least
      activity. When tested for extracellular activity, valnemulin (MICs ranging from
      0.125 to 4microg/ml) was the most active against most L. intracellularis
      isolates. Chlortetracycline (MICs ranging from 16 to 64microg/ml), tylosin (MICs
      ranging from 1 to >128microg/ml), and tiamulin (MICs ranging from 1 to
      32microg/ml) showed intermediate activities. Lincomycin (MICs ranging from 32 to
      >128microg/ml) showed the least activity. Our in vitro results showed that each
      L. intracellularis isolate had a different antimicrobial sensitivity pattern and
      these data can be utilized as an in vitro guideline for the further antimicrobial
      evaluation of field L. intracellularis isolates.

PMID- 18823724
TI  - Experimental transmission of field Anaplasma marginale and the A. centrale
      vaccine strain by Hyalomma excavatum, Rhipicephalus sanguineus and Rhipicephalus
      (Boophilus) annulatus ticks.
AB  - The cattle rickettsia Anaplasma marginale is distributed worldwide and is
      transmitted by about 20 tick species, but only Rhipicephalus simus, a strictly
      African tick species, has been shown to transmit the vaccine strain of A.
      centrale. The aim of the present study was to examine transmission of field
      strains of A. marginale and of the vaccine strain of A. centrale by three tick
      species -Hyalomma excavatum, Rhipicephalus sanguineus and Rhipicephalus
      (Boophilus) annulatus - to susceptible calves. Two genetically distinct Israeli
      field strains of A. marginale, tailed and non-tailed (AmIsT and AmIsNT,
      respectively), were efficiently transmitted by R. sanguineus, whereas H.
      excavatum transmitted only the tailed isolate, and R. (Boophilus) annulatus did
      not transmit A. marginale. None of the three tick species transmitted A.
      centrale. By means of msp1a primers in PCR assays, amplicons of similar sizes
      were obtained from either A. marginale-infected calves that were used for
      acquisition feeding, from R. sanguineus fed on the infected calves, or from
      calves to which anaplasmosis had been successfully transmitted by these ticks.
      Although an A. centrale-specific fragment was amplified from salivary glands of
      R. sanguineus, no transmission to susceptible cattle occurred during 3 months of
      observation, and anaplasmosis was not induced in splenectomized calves that were
      subinoculated with blood from calves on which R. sanguineus had fed.

PMID- 18823725
TI  - Infections with weakly haemolytic Brachyspira species in pigs with miscellaneous
      chronic diseases.
AB  - The prevalence of infections with different Brachyspira species was assessed in
      202 pigs with various chronic herd problems using different methods. Twenty-seven
      pigs (13.4%) were positive for Brachyspira spp. with at least one of the methods
      used. The highest number of positives was identified with mucosal scraping-PCR
      (23), followed by PET-PCR (22) and bacteriological-biochemical analysis (15).
      With the exception of three cases of B. pilosicoli infections, only weakly
      pathogenic Brachyspira species were identified. The majority was B. murdochii,
      followed by B. innocens and B. intermedia. Concurrent infections with two or more
      Brachyspira species were common and accounted for 37.1% of the total. Presence of
      weakly haemolytic Brachyspira was associated with wasting and diarrhoea in a
      number of cases. This investigation shows that infections with weakly haemolytic
      Brachyspira spp. may contribute to colonic pathology in pigs with chronic herd
      problems and that mixed infections seem to occur more frequently than previously
      noticed.

PMID- 18823726
TI  - Perinatal tuberculosis: new challenges in the diagnosis and treatment of
      tuberculosis in infants and the newborn.
AB  - With increasing rates of tuberculosis (TB) infection and disease worldwide, the
      rate of perinatal TB is also affected. A high index of suspicion by health
      professionals, in both the developed and developing world, is required to detect
      and manage tuberculosis in pregnancy and the early newborn period. Differences in
      immune responses in the fetus and neonate add to the diagnostic difficulties
      already recognised in young children. Although specific guidelines for the
      treatment of this potentially devastating disease are lacking due to paucity of
      experience, outcome is favourable, if the condition is recognised and treated
      according to existing TB protocols. HIV co-infection, multi- and extensively-drug
      resistant (MDR/XDR) TB contribute to the challenges. New diagnostic and vaccine
      developments hold future promise, but much work is needed to completely
      understand the complex immune responses to tuberculosis and control this disease.

PMID- 18823727
TI  - Expansion of the first polyalanine tract of the ARX gene in a boy presenting with
      generalized dystonia in the absence of infantile spasms.
AB  - Mutations in the Aristaless-related homeobox (ARX) gene are associated with
      pleiotropic phenotypes including infantile spasms, mental retardation and
      dystonia. However, relatively consistent genotype-phenotype correlations have
      been emphasized in prior reports. We report a boy presenting with mental
      retardation, tonic seizures and dystonia but without infantile spasms. Gene
      sequencing detected an additional seven GCG repeats in the first polyalanine
      tract of the ARX gene, a mutation which leads to an expansion of the normal 16
      alanine residues to 23. The same ARX gene mutation has been reported in patients
      with infantile spasms, but was absent in the present case. This finding
      highlights the diverse phenotypic spectrum that may result from ARX gene
      mutations.

PMID- 18823728
TI  - [An unusual case of congenital bronchoesophageal fistula in an adult patient].

PMID- 18823729
TI  - [Doxycycline induced hepatitis].

PMID- 18823730
TI  - GRAPPA-based susceptibility-weighted imaging of normal volunteers and patients
      with brain tumor at 7 T.
AB  - Susceptibility-weighted imaging (SWI) is a valuable technique for high-resolution
      imaging of brain vasculature that greatly benefits from the emergence of higher
      field strength MR scanners. Autocalibrating partially parallel imaging techniques
      can be employed to reduce lengthy acquisition times as long as the decrease in
      signal-to-noise ratio does not significantly affect the contrast between vessels
      and brain parenchyma. This study assessed the feasibility of a Generalized
      Autocalibrating Partially Parallel Acquisition (GRAPPA)-based SWI technique at 7
      T in both healthy volunteers and brain tumor patients. GRAPPA-based SWI allowed a
      twofold or more reduction in scan time without compromising vessel contrast and
      small vessel detection. Postprocessing parameters for the SWI needed to be
      modified for patients where the tumor causes high-frequency phase wrap artifacts
      but did not adversely affect vessel contrast. GRAPPA-based SWI at 7 T revealed
      regions of microvascularity, hemorrhage and calcification within heterogeneous
      brain tumors that may aid in characterizing active or necrotic tumor and
      monitoring treatment effects.

PMID- 18823731
TI  - Carr-Purcell-Meiboom-Gill imaging of prostate cancer: quantitative T2 values for
      cancer discrimination.
AB  - Quantitative, apparent T(2) values of suspected prostate cancer and healthy
      peripheral zone tissue in men with prostate cancer were measured using a Carr
      Purcell-Meiboom-Gill (CPMG) imaging sequence in order to assess the cancer
      discrimination potential of tissue T(2) values. The CPMG imaging sequence was
      used to image the prostates of 18 men with biopsy-proven prostate cancer. Whole
      gland coverage with nominal voxel volumes of 0.54 x 1.1 x 4 mm(3) was obtained in
      10.7 min, resulting in data sets suitable for generating high-quality images with
      variable T(2)-weighting and for evaluating quantitative T(2) values on a pixel-by
      pixel basis. Region-of-interest analysis of suspected healthy peripheral zone
      tissue and suspected cancer, identified on the basis of both T(1)- and T(2)
      weighted signal intensities and available histopathology reports, yielded
      significantly (P<.0001) longer apparent T(2) values in suspected healthy tissue
      (193+/-49 ms) vs. suspected cancer (100+/-26 ms), suggesting potential utility of
      this method as a tissue specific discrimination index for prostate cancer. We
      conclude that CPMG imaging of the prostate can be performed in reasonable scan
      times and can provide advantages over T(2)-weighted fast spin echo (FSE) imaging
      alone, including quantitative T(2) values for cancer discrimination as well as
      proton density maps without the point spread function degradation associated with
      short effective echo time FSE sequences.

PMID- 18823732
TI  - Semi-preparative HPLC preparation and HPTLC quantification of
      tetrahydroamentoflavone as marker in Semecarpus anacardium and its polyherbal
      formulations.
AB  - Application of modern scientific knowledge coupled with sensitive analytical
      technique is important for the quality evaluation and standardization of
      polyherbal formulations. Semecarpus anacardium, an important medicinal plant with
      wide medicinal properties, is frequently used in a large number of traditional
      herbal preparations. Tetrahydroamentoflavone (THA), a major bioactive biflavonoid
      was selected as a chemical marker of S. anacardium and RP-semi-preparative HPLC
      conditions were optimized for the isolation of tetrahydroamentoflavone. HPTLC
      analytical method was developed for the fingerprinting of S. anacardium
      flavonoids and quantification of tetrahydroamentoflavone. The method was
      validated in terms of their linearity, LOD, LOQ, precision and accuracy and
      compared with RP-HPLC-DAD method. The methods were demonstrated for the chemical
      fingerprinting of S. anacardium plant parts and some commercial polyherbal
      formulations and the amount of tetrahydroamentoflavone was quantified. HPTLC
      analysis showed that S. anacardium seed contained approximately 10 g kg(-1) of
      tetrahydroamentoflavone. The methods were able to identify and quantify
      tetrahydroamentoflavone from complex mixtures of phytochemicals and could be
      extended to the marker-based standardization of polyherbal formulations,
      containing S. anacardium.

PMID- 18823733
TI  - Cocaine-induced agitated delirium with associated hyperthermia: a case report.
AB  - BACKGROUND: "Cocaine-induced agitated delirium with associated hyperthermia" is a
      rare, almost uniformly fatal syndrome. The incidence of the disease is not known,
      however, it is believed to have markedly increased since the late 1980s with
      widespread popularity of crack cocaine. OBJECTIVE: Recent literature is lacking
      regarding this rare syndrome. Although almost uniformly fatal, we present a
      neurologically intact survivor due to a multidisciplinary team approach. CASE
      REPORT: We are reporting a 41-year-old African-American man who arrived at the
      trauma center with a rectal temperature of 42.6 degrees C (108.6 degrees F) and a
      toxicology screen positive for cocaine. The patient manifested many of the known
      complications of cocaine-induced agitated delirium with associated hyperthermia,
      including renal failure and coagulation panel abnormalities. With early
      application of cooling techniques, including ice pack, gastric lavage, and
      bilateral chest cavity lavage using multiple chest tubes, the patient's core
      temperature was quickly lowered. CONCLUSION: This case demonstrated how a
      multidisciplinary team approach, including emergency medicine and critical care
      specialists, and aggressive treatment of hyperthermia using bilateral tube
      thoracostomy and chest cavity lavage enabled our patient's core temperature to be
      effectively lowered. We were unable to find prior reports of using tube
      thoracostomy in this manner.

PMID- 18823734
TI  - Enhancing the diagnostic performance of troponins in the acute care setting.
AB  - BACKGROUND: Current guidelines define cardiac troponin I (TnI) as an indicator of
      necrosis when the concentration exceeds the 99% upper limit of a healthy
      reference population, a reference value near the assay's lowest detectable level.
      We assessed the utility of a modified TnI cutoff point derived from a population
      at low risk for coronary artery disease (CAD) and evaluated its utility in
      determining acute myocardial infarction (MI). METHODS: A modified TnI cutoff
      point was derived by the receiver operating characteristic (ROC) curve from 737
      consecutive patients who underwent serial TnI measurements for exclusion of MI.
      Creatinine kinase isoenzyme MB (CK-MB) evolutionary change was used to define MI.
      The new derived cutoff point was validated using another subset of 320 patients
      who were evaluated for MI. RESULTS: ROC-derived TnI cutoff point (A) was 0.65
      MUg/L, and its performance was compared to the recommended cutoff point ([B] 0.15
      MUg/L). Cutoff point A had greater specificity (94.5% vs. 86.9%, p < 0.001) but
      slightly lower sensitivity (96.5% vs. 100%, p < 0.01). Cutoff point A provided
      significantly greater positive predictive value (PPV) for MI (74.1% vs. 55.5%, p
      < 0.0001) and fewer false-positive errors, while preserving comparable negative
      predictive value (NPV) (98.9% vs. 100%). CONCLUSION: A higher cutoff point
      derived from a reference population of patients at low risk for CAD may improve
      the TnI performance assay. The PPV for diagnosis of MI was significantly higher
      and false-positive values were fewer without affecting the NPV. The more reliable
      diagnosis of MI may have resulted, which, in turn, may have significant clinical
      and economic implications.

PMID- 18823735
TI  - National study on the frequency, types, causes, and consequences of voluntarily
      reported emergency department medication errors.
AB  - BACKGROUND: Medication errors contribute to significant morbidity, mortality, and
      costs to the health system. Little is known about the characteristics of
      Emergency Department (ED) medication errors. STUDY OBJECTIVE: To examine the
      frequency, types, causes, and consequences of voluntarily reported ED medication
      errors in the United States. METHODS: A cross-sectional study of all ED errors
      reported to the MEDMARX system between 2000 and 2004. MEDMARX is an anonymous,
      confidential, de-identified, Internet-accessible medication error-reporting
      program designed to allow hospitals to report, track, and share error data in a
      standardized format. RESULTS: There were 13,932 medication errors from 496 EDs
      analyzed. The error rate was 78 reports per 100,000 visits. Physicians were
      responsible for 24% of errors, nurses for 54%. Errors most commonly occurred in
      the administration phase (36%). The most common type of error was improper
      dose/quantity (18%). Leading causes were not following procedure/protocol (17%),
      and poor communication (11%), whereas contributing factors were distractions
      (7.5%), emergency situations (4.1%), and workload increase (3.4%). Computerized
      provider order entry caused 2.5% of errors. Harm resulted in 3% of errors.
      Actions taken as a result of the error included informing the staff member who
      committed the error (26%), enhancing communication (26%), and providing
      additional training (12%). Patients or family members were notified about
      medication errors 2.7% of the time. CONCLUSION: ED medication errors may be a
      result of the acute, crowded, and fast-paced nature of care. Further research is
      needed to identify interventions to reduce these risks and evaluate the
      effectiveness of these interventions.

PMID- 18823736
TI  - Acute multi-vessel coronary stent thrombosis.
AB  - BACKGROUND: Coronary artery stent thrombosis is a rare but often fatal
      complication associated with percutaneous coronary intervention (PCI) using both
      bare-metal stents and drug-eluting stents. Although strict adherence to dual anti
      platelet therapy (aspirin plus clopidogrel) minimizes this risk, stent thrombosis
      will still occur in rare patients, leading to acute, subacute, or late life
      threatening acute coronary syndromes. OBJECTIVES: To present a rare case of acute
      stent thrombosis involving multiple vessels to increase awareness of this life
      threatening condition among emergency physicians, and to review the current
      guidelines for anti-platelet therapy in this patient population. CASE REPORT: A
      52-year-old man who underwent PCI using drug-eluting stents in two separate
      coronary vessels presented to the Emergency Department within 2 h of discharge
      from the hospital with chest pain, dynamic electrocardiogram changes, and
      elevated cardiac markers. Despite compliance with the current recommendations for
      post-PCI anti-platelet therapy, urgent repeat catheterization revealed total
      thrombotic occlusion of both stents, requiring urgent repeat intervention.
      CONCLUSION: Despite patient compliance with the currently recommended anti
      platelet regimen after stent therapy for coronary artery disease, acute stent
      thrombosis remains a rare but life-threatening risk in both the immediate and
      delayed post-intervention period. In addition, premature cessation of this anti
      platelet therapy stands as the greatest risk factor for such thrombotic events.
      This case is presented to inform emergency physicians of the current post-PCI
      anticoagulation recommendations to help mitigate the risk of such complications.

PMID- 18823737
TI  - Role of biographical experience and bodily sensations in patients' adaptation to
      hypertension.
AB  - OBJECTIVE: To explore patients' adaptation to hypertension and to describe its
      impact on their sense of body, biographical experience, approach to life and
      daily activities. METHODS: A qualitative interview study with nine men and eight
      women (age: 35-50 years) with hypertension from four general practices in
      Denmark. The informants differed in type and duration of treatment. RESULTS:
      Adaptation to hypertension was influenced by the patients' biographical
      experiences and involved changes in body perception. The process affected
      patients' daily activities and they actively tested their physical abilities.
      Patients gradually adopted behaviour and attitudes to reduce their risk of
      cardiovascular disease. CONCLUSION: A diagnosis of hypertension constitutes a
      biographical disruption and has an impact on daily life. Patients' adaptation to
      hypertension combines biographical and bodily experiences. PRACTICE IMPLICATIONS:
      Attention to patients' biographies and images of hypertension is an important
      element of hypertensive treatment.

PMID- 18823738
TI  - Development of an antisense RNA delivery system using conjugates of the MS2
      bacteriophage capsids and HIV-1 TAT cell-penetrating peptide.
AB  - RNA-based therapeutic strategies are used widely due to their highly specific
      mode of action. However, the major obstacle in any RNA-based therapy is cellular
      delivery and stability in the cells. The self-assembly of the MS2 bacteriophage
      capsids has been used to develop virus-like particles (VLPs) for drug delivery.
      In this study, we utilized the heterobifunctional crosslinker, sulfosuccinimidyl
      4-(p-maleimidophenyl)-butyrate (sulfo-SMPB), to conjugate the human
      immunodeficiency virus-1 (HIV-1) Tat peptide and MS2 VLPs; the antisense RNA
      against the 5'-untranslated region (UTR) and the internal ribosome entry site
      (IRES) of the hepatitis C virus (HCV) was packaged into these particles by using
      a two-plasmid coexpression system. The MS2 VLPs conjugated with the Tat peptide
      were then transferred into Huh-7 cells containing an HCV reporter system. The
      packaged antisense RNA showed an inhibitory effect on the translation of HCV.
      This paper describes our initial results with this system using the Tat peptide.

PMID- 18823739
TI  - Vascular endothelial dysfunction: a tug of war in diabetic nephropathy?
AB  - Vascular endothelium regulates vascular tone and maintains free flow of blood in
      vessels. Vascular endothelial dysfunction (VED) results in reduced activation of
      endothelial nitric oxide synthase (eNOS), reduced generation and bioavailability
      of nitric oxide (NO) and increased production of reactive oxygen species (ROS).
      The eNOS uncoupling in VED leads to eNOS mediated production of ROS that further
      damage the endothelial cells by upregulating the proinflammatory mediators and
      adhesion molecules. VED has been associated in the pathogenesis of hypertension,
      atherosclerosis, coronary artery diseases, diabetes mellitus and nephropathy.
      Diabetes is a chronic metabolic disorder characterized by hyperglycemia followed
      by micro and macrovascular complications. A correlation between diabetes and VED
      has been demonstrated in various studies. The downregulation of eNOS in diabetes
      has been noted to accelerate diabetic nephropathy. Moreover, various endogenous
      vasoconstrictors are also upregulated in diabetic nephropathy. VED has been shown
      to be involved in diabetic nephropathy by inducing nodular glomerulosclerosis
      followed by glomerular basement membrane thickness and mesangial expansion, which
      ultimately decline glomerular filtration rate (GFR). Thus it is suggested that
      diabetes-induced VED could be one of the culprits involved in the pathogenesis of
      diabetic nephropathy.

PMID- 18823740
TI  - [Chronic obstructive pulmonary disease exacerbations and their impact on the long
      term natural history of the disease].
AB  - Exacerbations can occur at each stage of chronic obstructive pulmonary disease
      (COPD), but their frequency and severity increase with disease progression. Today
      exacerbations are known to have severe immediate and delayed consequences. They
      aggravate symptoms (dyspnea, cough, and sputum), airflow, and FEV1 decline and
      impair quality of life--all durably, with prolonged recovery time. They increase
      the risk of death. Their economic consequences are substantial, accounting for
      60% of direct cost associated with COPD - 3 and 9 billion euros per year.
      Prevention of exacerbations is a major public health objective and is an integral
      part of the COPD program defined by French health authorities for the 2005-2010
      period. It is essential to improve quality of life and prevent worsening of the
      long-term course of COPD.

PMID- 18823741
TI  - Pull-out strength of a polished tapered stem is improved by placing bone cement
      over the shoulder of the implant.
AB  - Displacement of a polished stem while attempting closed reduction of a dislocated
      total hip or during dislocation itself is a rare but significant complication.
      Our aim was to assess whether applying bone cement over the shoulder of the
      implant can help to prevent this. We conducted an in vitro mechanical study with
      tensile testing machine. We cemented 7 sawbones with a standard cementing
      technique and another 7 with additional cement over the shoulder of the implant.
      The mean pull-out force in the routine cementing technique was 2066 N (SD,
      256.65), and it was 3220 N (SD, 312.22) for the group with the cement on the
      shoulder. There is a statistically significant difference of 1154 N. We recommend
      that when a polished stem is used, bone cement should be applied over the
      shoulder of the implant.

PMID- 18823742
TI  - Metal-on-metal hip resurfacing: the effect of cup position and component size on
      range of motion to impingement.
AB  - The aim of this dry bone study was to determine the range of hip motion to
      impingement for different hip resurfacing cup positions and component sizes. The
      maximum angles of hip flexion, extension, abduction, and adduction were
      calculated from 3-dimensional coordinates for: 1. Cup inclination of 30 degrees ,
      40 degrees , 50 degrees , 60 degrees , and 70 degrees with fixed anteversion; 2.
      Cup anteversion of 0 degrees , 10 degrees , 25 degrees , 35 degrees , and 45
      degrees with fixed inclination; and 3. 3 different component sizes on the same
      size dry bones. An acetabular component inclination of 50 degrees and an
      anteversion of 25 degrees allowed the most physiologic range of hip motion. A
      larger-diameter femoral component relative to the native femoral neck diameter
      resulted in a greater range of hip motion to impingement.

PMID- 18823743
TI  - Impact of medial opening or lateral closing tibial osteotomy on bone resection
      and posterior cruciate ligament integrity during knee arthroplasty.
AB  - To compare lateral closing to medial opening wedge high tibial osteotomy
      regarding change in proximal tibial anatomy and PCL tibial attachment integrity
      after standard tibial arthroplasty resection. Controlled cadaveric study. Ten
      cadaveric lower limbs received either a 12 degrees lateral closing or 12.5-mm
      medial opening wedge high tibial osteotomy. Radiographs were performed before and
      after each osteotomy, and each PCL tibial attachment was dissected.
      Postosteotomy, tibial arthroplasty resection was performed and the remaining PCL
      attachment area calculated. Lateral closing wedge specimens demonstrated a
      greater change in proximal tibial anatomy. After tibial arthroplasty resection,
      there was a significant difference in remaining PCL tibial attachment percentage
      area. Proximal tibial anatomy is altered differently for each type of osteotomy
      despite similar correction angles. Arthroplasty conversion may be more
      challenging after lateral closing wedge procedures.

PMID- 18823744
TI  - Elevated serum concentrations of cobalt, chromium, nickel, and manganese after
      metal-on-metal alloarthroplasty of the hip: a prospective randomized study.
AB  - In this prospective randomized study, we investigate metal ion concentrations and
      clinical outcome 2 years after metal-on-metal (28 patients) or metal-on
      polyethylene (26 patients) hip arthroplasty with 28-mm modular heads. Metal ion
      concentrations in patient serum were analyzed by high-resolution plasma mass
      spectrometry. The clinical outcome was almost identical in both groups with
      respect to the Harris hip score and the Medical Outcome Study Short Form-36; and
      on plain radiography, no signs of loosening occurred in any group. In the metal
      on-metal group, concentrations of all investigated ions increased significantly
      when compared with preoperative values: cobalt, 15.3-fold (95% confidence
      interval [CI], 9.4-21.2); chromium, 5.2-fold (CI, 3.5-7.0); nickel, 2.1-fold (CI,
      1.2-3.0); and manganese, 1.6-fold (CI, 1.3-2.0). In the metal-on-polyethylene
      group, a smaller but significant increase in the concentrations of cobalt and
      nickel occurred, whereas concentrations of the other ions did not change
      significantly.

PMID- 18823745
TI  - Acetabular component revision using a porous tantalum biomaterial: a case series.
AB  - Biologic ingrowth can be difficult to achieve in acetabular component revision,
      especially in cases with significant bone loss. The purpose of this study was to
      review our clinical results of acetabular component revisions in patients with
      significant bone loss using a porous tantalum biomaterial. This is a
      retrospective review of 25 patients. There were 16 females and 9 males with a
      mean age of 71.7 +/- 10.54 years. The mean follow up was 39 +/- 11.09 months
      (range, 28-55 months). All patients in this series had combined segmental and
      cavitary bone loss, Paprosky type 2 or type 3. Of 22 patients in this series, 21
      had a well-fixed and functioning implant at latest follow up. All 21 patients
      developed ingrowth along the tantalum surface despite compromised host bone.
      There were no cases of dislocation or aseptic loosening. Porous tantalum appears
      to be a promising material for use in revision hip arthroplasty to facilitate
      biologic ingrowth in patients with acetabular bone loss.

PMID- 18823746
TI  - Three-dimensional tibiofemoral kinematics during deep flexion kneeling in a
      mobile-bearing total knee arthroplasty.
AB  - Achieving very deep flexion after total knee arthroplasty is an important goal of
      most patients in Japan, Asia, and the Middle East because of floor-sitting
      lifestyles. Numerous knee arthroplasty designs have been introduced to permit
      high flexion. We performed an in vivo radiographic analysis of tibiofemoral
      motions during weight-bearing kneeling in one high-flexion knee arthroplasty
      design. Twenty knees implanted with a posterior-stabilized rotating-platform knee
      arthroplasty flexed an average of 126 degrees. The femoral condyles translated
      posteriorly from extension to maximum flexion. Total posterior condylar
      translations averaged 11.6 and 4.7 mm for the lateral and medial condyles,
      respectively. Tibial internal rotation in 19 knees averaged 9 degrees from
      extension to maximum flexion. Knees implanted with a posterior-stabilized,
      rotating-platform knee arthroplasty show deep flexion knee kinematics consistent
      with the implant design intent.

PMID- 18823747
TI  - Role of surgical position on interface stress and initial bone remodeling
      stimulus around hip resurfacing arthroplasty.
AB  - Valgus alignment of femoral resurfacing components has been advocated to reduce
      proximal femur loading and thus minimize the risk for femoral neck fractures.
      However, such reduction in loading may exacerbate undesirable stress shielding.
      This study examined the effect of extreme implant orientations (+/-15 degrees )
      and stem canal overreaming on initial bone remodeling stimulus using finite
      element models. The changes in implant-cement interface stresses due to implant
      alignment were also evaluated. The valgus model showed increased initial bone
      resorption stimulus, which extended distally and peripherally around the femoral
      neck. The peak implant-cement interface shear stress for the varus model was 10.9
      MPa, exceeding the interface shear strength. Overreaming of the stem canal
      eliminated distal tip loading, but proximal stress shielding was still
      unavoidable. These data show bone loading and interface fixation trends emanating
      from valgus and varus implant positions that will be of interest to practicing
      physicians.

PMID- 18823748
TI  - Antibiotic bone cement and the incidence of deep infection after total knee
      arthroplasty.
AB  - We asked if the use of antibiotic-laden bone cement (ALBC) decreased the deep
      infection rate after primary total knee arthroplasty as compared to plain bone
      cement. We surveyed 1625 consecutive patients for relevant covariates. Joint pain
      and function were assessed at baseline and at 1 year of follow-up with the
      Western Ontario McMaster University Osteoarthritis Index scores. The incidence of
      deep infection at 1-year follow-up was recorded. There were no differences in
      baseline covariates between groups (P > .05). We found a deep infection rate of
      2.2% in the ALBC group and 3.1% in the plain bone cement group (P = .27).
      Adjusted analysis showed that ALBC was not predictive of a lower infection rate
      at 1 year (P = .84). Antibiotic-laden bone cement did not reduce the incidence of
      deep infection following primary total knee arthroplasty at 1-year follow-up.

PMID- 18823749
TI  - Porous tantalum cones for large metaphyseal tibial defects in revision total knee
      arthroplasty: a minimum 2-year follow-up.
AB  - Sixteen cases of revision total knee arthroplasty requiring the use of porous
      tantalum tibial cones for 2 T2A, 3 T2B, 4 T3A, and 7 T3B tibial bone defects
      (Anderson Orthopaedic Research Institute classification) after 13 cases of
      aseptic loosening and 3 cases of staged reimplantation for infection were
      reviewed. At an average 31 months (24-38), no patients were lost to follow-up.
      There were 2 cases of recurrent sepsis requiring removal of a well-fixed cone. In
      the remaining 14 cases, the reconstructions were functioning well with no
      reoperations. Radiographs demonstrated reestablishment of the joint line, neutral
      mechanical axis (average, 5.4 degrees of valgus), and signs of stable
      osteointegration into the cones. Good short-term results were achieved in complex
      revisions, with these new reconstructive tools.

PMID- 18823750
TI  - A comparative review of palliative care development in six countries represented
      by the Middle East Cancer Consortium (MECC).
AB  - Palliative care development and services were reviewed in the region represented
      by the six members of the Middle East Cancer Consortium: Cyprus, Egypt, Israel,
      Jordan, the Palestinian Authority, and Turkey. The multimethod review synthesized
      evidence from ethnographic field visits to inpatient units, home care hospice
      teams and free-standing hospices, including interviews with hospice and
      palliative care clinicians, administrators, volunteers, policy makers and
      academic researchers. Public health data and relevant literature were collated
      together with internet-accessed information on services and health care systems.
      A total of 69 services were located; two country members have a history of
      relatively sustained development of hospice and palliative care, but provision
      across the Middle East Cancer Consortium region is highly variable at a local
      level. Considerable barriers to service development were identified in a region
      already struggling with many military and political conflicts. Key problems are a
      lack of secure funds and government support, inadequate professional training
      programs, opioid phobia in professionals and the public, and a lack of awareness
      and understanding of palliative care needs at public, government, and
      professional levels. Key areas for further attention were increasing national and
      international professional training and public education programs, improving
      opioid legislation and health care policies, negotiating for secure government or
      health insurance funding provision, raising awareness about the need for
      pediatric services and for patients with other illnesses, as well as for those
      with cancer, and working to integrate palliative care into mainstream health
      service provision and education.

PMID- 18823751
TI  - Predicting survival with the Palliative Performance Scale in a minority-serving
      hospice and palliative care program.
AB  - Palliative Performance Scale (PPS) scores have shown potential for
      prognosticating survival in Caucasian samples, but have not been studied for
      prognostic value in cancer patients from minority groups. Using data obtained
      from a retrospective chart audit of 492 cancer patients admitted over an 18-month
      period to a minority-serving home-based hospice and palliative care program, we
      examined the relationship between PPS scores and length of survival (survival
      days). Patients with PPS scores of 10% to 30% had fewer survival days than those
      with scores of 40% and those with scores of 50% to 100% (median=6, 19, and 34
      days, respectively; F=25.02, P<0.001). A PPS score of 40% serves as a reliable
      inclusion criterion for a study requiring two weeks for completion, whereas 50%
      to 100% is required for a three-week study. Findings from a predominantly
      minority sample are similar to those from predominantly Caucasian samples.

PMID- 18823752
TI  - Adhesive arachnoiditis following percutaneous cervical cordotomy--may we still
      use lipiodol?

PMID- 18823753
TI  - Physical and mental health status of staff working for people with intellectual
      disabilities in Taiwan: measurement with the 36-Item Short-Form (SF-36) health
      survey.
AB  - Little explicit attention has been given to the generic health profile of staff
      working for people with intellectual disability in institutions. This study aimed
      to provide a profile of physical and mental health of staff working in disability
      welfare institutions, and to examine the possible demographic and organizational
      factors that explain an association with their health. A cross-sectional
      questionnaire survey was conducted to analyze 1243 staff (76% response rate)
      working in 24 institutions in Taiwan. The 36-Item Short-Form (SF-36) Taiwan
      version was used to measure their generic health status. The mean of Physical
      component scores (PCS) was slightly higher than Mental component scores (MCS)
      (50.83 vs. 45.12). With regard to each dimension among PCS, the mean score of
      Physical functioning (PF) was 57.14 (S.D.=5.93), Role limitations-physical (RP)
      was 49.88 (S.D.=9.69), Bodily pain (BP) was 52.14 (S.D.=8.09) and General medical
      health (GH) was 51.50 (S.D.=8.28). Among the MCS, Vitality (VT) was 46.19
      (S.D.=6.71); Social functioning (SF) was 46.44 (S.D.=7.58); Role limitations
      emotional (RE) was 47.30 (S.D.=11.89) and Mental health (MH) was 43.58
      (S.D.=8.81). We found the generic health of staff working for people with
      intellectual disabilities were significantly lower in PCS and MCS than the Taiwan
      general population. Influences of staff's demographic and organizational
      characteristics on their health were also analyzed in the content. This study
      highlights the authorities and service providers need to continue to develop
      their awareness and understanding of the experiences that their staff encounters
      in the organizations, so that they can receive resources to support their
      positive health in working for people with intellectual disabilities.

PMID- 18823754
TI  - AHRQ series paper 4: assessing harms when comparing medical interventions: AHRQ
      and the effective health-care program.
AB  - Comparative effectiveness reviews (CERs) are systematic reviews that evaluate
      evidence on alternative interventions to help clinicians, policy makers, and
      patients make informed treatment choices. Reviews should assess harms and
      benefits to provide balanced assessments of alternative interventions.
      Identifying important harms of treatment and quantifying the magnitude of any
      risks require CER authors to consider a broad range of data sources, including
      randomized controlled trials (RCTs) and observational studies. This may require
      evaluation of unpublished data in addition to published reports. Appropriate
      synthesis of harms data must also consider issues related to evaluation of rare
      or uncommon events, assessments of equivalence or noninferiority, and use of
      indirect comparisons. This article presents guidance for evaluating harms when
      conducting and reporting CERs. We include suggestions for prioritizing harms to
      be evaluated, use of terminology related to reporting of harms, selection of
      sources of evidence on harms, assessment of risk of bias (quality) of harms
      reporting, synthesis of evidence on harms, and reporting of evidence on harms.

PMID- 18823755
TI  - Potential for technical errors and subverted allocation can be reduced if certain
      guidelines are followed: examples from a web-based survey.
AB  - OBJECTIVE: To elicit researchers' experiences and knowledge of how the
      randomization process can be undermined. STUDY DESIGN AND SETTING: Web-based
      survey conducted in February 2006 using a convenience sample of individuals who
      are, or have been, involved in some aspect of randomized controlled trials.
      RESULTS: Thirty responses were received that described incidences of
      manipulation. Seven reasons were identified for manipulation: interest of
      participants, demonstrating treatment efficacy, treatment preference, lack of
      knowledge, pressure from participants, pressure from trial workers, and practical
      or technical concerns. In many cases when manipulation was discovered, it was
      rarely mentioned in the trial publication. Twenty-three responses that described
      technical errors were received. Technical errors were reported for both the
      generation and implementation stages of the randomization process. CONCLUSIONS:
      This study provides further evidence on trial subversion and highlighted that the
      potential for technical errors can be reduced, and in most cases eliminated, if
      certain guidelines are followed. Recommendations are as follows: use simple
      randomization where possible, use third party allocation, test computer
      randomization programs prior to participant recruitment and ensure that
      individuals are aware of the procedures needed to be performed if the treatment
      allocations cannot be accessed using the intended methods.

PMID- 18823756
TI  - Effect of acute and chronic photoperiod modulation on pentylenetetrazole-induced
      clonic seizure threshold in mice.
AB  - Changes in circadian rhythms have been shown to alter seizure susceptibility and
      anticonvulsant properties of drugs. The present study attempts to elucidate the
      effect of acute and chronic light/dark (LD) cycle alterations on
      pentylenetetrazol-induced clonic seizure threshold (CST) in male NMRI mice. The
      acute effect was tested by comparing the effects of abrupt 6-h phase shifts that
      resulted in 6-h and 18-h photoperiods, during the 24-h period before CST
      determination, with the controls that were maintained on 12h/12h LD cycle. In
      order to test the effect of chronic LD cycle alteration on CST, three groups of
      mice were maintained on 12h/12h, 6h/18h and 18h/6h LD cycles for 2 weeks prior to
      CST testing. The effect of administration of exogenous melatonin (5, 10 and
      20mg/kg, i.p.) was also assessed on LD cycle related changes of CST. The results
      indicate that acute photoperiod change from 12h/12h to 18h/6h LD cycle lowers
      CST, while keeping animals under shorter photoperiod does not produce a
      significant effect. The pro-convulsant effect of acute increase in light period
      is reversed by a single injection of melatonin (10 and 20mg/kg). Animals
      chronically maintained on both shorter and longer photoperiods show a significant
      decrease in CST compared to animals under 12h/12h LD cycle. However, in both
      groups chronic administration of melatonin (20mg/kg) reversed the effect of LD
      cycle alteration on CST. In conclusion, our data demonstrate that acute increase
      and chronic modulation of the photoperiod increase seizure susceptibility in
      mice. Moreover, the pro-convulsant effect of LD cycle alteration could be
      reversed by exogenous melatonin administration.

PMID- 18823757
TI  - Association of Sult4A1 SNPs with psychopathology and cognition in patients with
      schizophrenia or schizoaffective disorder.
AB  - A number of genes located on chromosome 22q11-13, including catechol-O
      methyltransferase (COMT), are potential schizophrenia susceptibility genes.
      Recently, the sulfotransferase-4A1 (Sult4A1) locus within chromosome 22q13 was
      reported to be linked to schizophrenia in a family TDT study. Sult4A1 is related
      to metabolism of monoamines, particularly dopamine and norepinephrine, both of
      which have been implicated in the pathophysiology of the psychopathology and
      cognitive dysfunction components of schizophrenia. An available, prospectively
      collected data base was interrogated to determine how three Sult4A1 SNPs:
      rs138060, rs138097, and rs138110, previously shown to be associated with
      schizophrenia might be associated with psychopathology, cognition, and quality of
      life in a sample of 86 Caucasian patients with schizophrenia or schizoaffective
      disorder. The majority of patients met criteria for treatment resistant
      schizophrenia and had been drug-free for one week or longer at the time of
      evaluation. The major findings were: 1) patients heterozygous (T/G) for rs138060
      had significantly worse Brief Psychiatric Rating Scale (BPRS) Total and
      anxiety/depression sub-scale scores, and higher Scale for the Assessment of
      Positive Symptoms (SAPS) Total scores than G/G homozygous patients; and 2)
      patients heterozygous (A/G) for rs138097 demonstrated significantly worse
      performance on neuropsychological testing, specifically on tests of executive
      function and working memory, compared to patients homozygous for the G and A
      alleles. RS138110 was unrelated to psychopathology and cognition. These results
      provide the first evidence of how genetic variation in Sult4A1 may be related to
      clinical symptoms and cognitive function in schizophrenia, and permit future
      studies to attempt to replicate these potentially important findings.

PMID- 18823758
TI  - Dipeptidyl peptidase II is not a marker for progression in melanoma.

PMID- 18823759
TI  - A cost analysis of Outpatient Parenteral Antibiotic Therapy (OPAT): an Asian
      perspective.
AB  - The concept of Outpatient Parenteral Antibiotic Therapy (OPAT) is relatively new
      in Asia. This study compared the actual costs and outcomes of care involving OPAT
      with conventional inpatient-only care at a university hospital in Singapore.
      Actual costs were obtained for selected patients enrolled in OPAT after 1 January
      2005 and these costs were directly compared with those of age-, gender- and
      diagnosis-matched patients managed as inpatients only prior to the availability
      of OPAT in the preceding 12 months. Outcomes of patients were also considered.
      The OPAT and inpatient-only groups comprised 72 and 93 enrollments, respectively.
      Mean treatment duration for OPAT patients was 42.5 days versus 19 days for those
      receiving inpatient-only care (P < 0.001). The mean total treatment cost for OPAT
      and inpatient-only care was US$12 736 and $12 403, respectively (P = 0.706). Mean
      cost per day for care including an OPAT episode was US$278 versus $457 per day
      for inpatient-only care (P < 0.001). There was no difference in outcomes between
      the two groups. OPAT is a viable alternative to inpatient care as it is safe,
      effective and results in lower daily costs. The trend to longer treatment courses
      is worthy of further review.

PMID- 18823760
TI  - Does the probability of receiving placebo influence clinical trial outcome? A
      meta-regression of double-blind, randomized clinical trials in MDD.
AB  - Substantial and highly variable placebo response rates represent a major obstacle
      to antidepressant development in major depressive disorder (MDD). However,
      whether the likelihood of receiving active treatment or placebo, a proxy of the
      degree of expectation of improvement, may itself influence clinical trial outcome
      is unclear. The goal of this work was to examine whether the probability of
      receiving placebo influences clinical trial outcome antidepressant MDD trials.
      Medline/Pubmed publication databases were searched for randomized, double-blind,
      placebo-controlled trials of antidepressants for adults with MDD. 146 manuscripts
      involving 182 clinical trials were pooled (n = 36,385). Pooled response rates for
      drug and placebo were 53.8% and 37.3%. A meta-regression (random-effects)
      established that the probability of receiving placebo, year of publication, and
      baseline severity were independent predictors of the risk ratio of responding to
      antidepressants versus placebo. Specifically, a greater probability of receiving
      placebo, greater baseline severity and an earlier year of publication predicted
      greater antidepressant-placebo "efficacy separation". Fixed versus flexible dose
      design, trial duration and population age did not influence clinical trial
      outcome.

PMID- 18823761
TI  - Electrochemical behavior of valsartan and its determination in capsules.
AB  - Electrochemical behavior of valsartan has been carried out in Britton-Robinson (B
      R) buffer solution at pH 7.0 at the mercury film electrode (MFE) by cyclic,
      linear sweep, differential-pulse and square-wave voltammetry. The property of
      valsartan adsorption at the MFE using accumulation potential of +0.10 V was
      observed. The effects of experimental parameters on electrochemical process at
      the MFE were discussed. Differential-pulse adsorptive stripping and square-wave
      adsorptive stripping voltammetry for the valsartan determination were proposed,
      linearity was found in the range of 6.0 x 10(-8) to 4.0 x 10(-6)mol/L. The
      detection limits were 2.93 x 10(-9) and 3.27 x 10(-9)mol/L, respectively. The
      proposed methods were also applied to the commercial valsartan with good
      recoveries.

PMID- 18823762
TI  - Electrochemical properties of niosomes modified Au electrode and DNA recognition.
AB  - Non-ionic surfactant vesicles (NSVs), also referred to as niosomes, have been
      studied as an alternative to conventional liposomes. In this paper,
      electrochemical inspection of the interaction between Herring sperm DNA and
      niosomes has been investigated after a simple and novel method for the formation
      of niosomes on Au electrode. Each step of electrode modification has been
      confirmed with cyclic voltammetry (CV) and electrochemical impedance spectroscopy
      (EIS). The assembly of octadecanethiol (ODT) layer on the electrode surface
      generates a packed film that introduces a barrier to the interfacial electron
      transfer (R(et)), and the subsequent immobilization of niosomes onto the self
      assembled monolayer (SAM) layer results in a further increase of R(et), due to
      the formed bilayer almost blocked the redox probe to the electrode surface. When
      Herring sperm DNA was added, the R(et) value decreased, indicating that the
      barrier of the redox probe to the surface was disrupted. The addition of DNA
      caused the formation of some transmembrane channels for the redox probe across
      the niosomes. A good linear relationship between R(et) value and DNA
      concentration was found over the 0-0.05 mg mL(-1) concentration range.

PMID- 18823763
TI  - [Pulmonary function testing in children].
AB  - Pulmonary function testing in child can be realized in different circumstances:
      to confirm a diagnosis (asthma), to monitor evolution of a chronic pulmonary
      disease (asthma, bronchodysplasia, mucovicidosis...) or to quantify a possible
      pulmonary dysfunction in various pathologies (immune defect, dermatomyositis,
      scoliosis, drepanocytosis...).

PMID- 18823764
TI  - Modeling adaptive kernels from probabilistic phylogenetic trees.
AB  - OBJECTIVE: Modeling phylogenetic interactions is an open issue in many
      computational biology problems. In the context of gene function prediction we
      introduce a class of kernels for structured data leveraging on a hierarchical
      probabilistic modeling of phylogeny among species. METHODS AND MATERIALS: We
      derive three kernels belonging to this setting: a sufficient statistics kernel, a
      Fisher kernel, and a probability product kernel. The new kernels are used in the
      context of support vector machine learning. The kernels adaptivity is obtained
      through the estimation of the parameters of a tree structured model of evolution
      using as observed data phylogenetic profiles encoding the presence or absence of
      specific genes in a set of fully sequenced genomes. RESULTS: We report results
      obtained in the prediction of the functional class of the proteins of the budding
      yeast Saccharomyces cerevisae which favorably compare to a standard vector based
      kernel and to a non-adaptive tree kernel function. A further comparative analysis
      is performed in order to assess the impact of the different components of the
      proposed approach. CONCLUSIONS: We show that the key features of the proposed
      kernels are the adaptivity to the input domain and the ability to deal with
      structured data interpreted through a graphical model representation.

PMID- 18823765
TI  - Immunohistochemical study on the distribution of insulin-like growth factor
      binding protein 4 in the central nervous system of SOD1(G93A) transgenic mice as
      an in vivo model of amyotrophic lateral sclerosis.
AB  - In the present study, we used the SOD1(G93A) mutant transgenic mice as an in vivo
      model of amyotrophic lateral sclerosis (ALS) and performed immunohistochemical
      studies to investigate the changes of insulin-like growth factor-binding protein
      4 (IGFBP4) in the central nervous system. Decreased expression of IGFBP4 was
      obvious in the cerebral cortex, hippocampus, cerebellar cortex and inferior olive
      of SOD1(G93A) transgenic mice. In the cerebral cortex, there was a significant
      decrease in IGFBP4 immunoreactivity in the pyramidal cells. In the hippocampal
      formation, IGFBP4 immunoreactivity was also decreased in the pyramidal cells of
      CA1-3 areas and the granule cells of dentate gyrus. In the cerebellar cortex,
      IGFBP4 immunoreactivity was prominent in the granular layer in wtSOD1 transgenic
      mice, compared to that in SOD1(G93A) transgenic mice. IGFBP4 immunoreactivity was
      decreased in the inferior olive of SOD1(G93A) transgenic mice. This study,
      showing decreased IGFBP4 in different brain regions of SOD1(G93A) transgenic
      mice, may provide clues to understanding the differential susceptibility of
      neural structures in ALS, suggesting a role of IGFBP4 in an abnormality of
      cognitive and/or motor function in ALS. The mechanisms and functional
      implications of these decreases require elucidation.

PMID- 18823766
TI  - Detection of biological macromolecules on a biochip dedicated to UV specific
      absorption.
AB  - This work describes an ultraviolet biosensing technique based on specific
      molecular absorption detected with a previously developed spectrally selective
      aluminum gallium nitride (AlGaN) based detector. Light absorption signal of DNA
      and proteins, respectively at 260 nm and 280 nm, is used to image biochips. To
      allow detection of protein or DNA monolayers at the surface of a biochip, we
      develop contrast-enhancing multilayer substrates. We analyze them through models
      and experiments and validate the possibility of measuring absorptions of the
      order of 10(-3). These multilayer structures display a high reflectivity, and
      maximize the interaction of the electric field with the biological element at the
      chip surface. Optimization of the experimental absorption, which includes effects
      such as roughness of the biochip, spectral and angular resolution of the optics,
      illumination, etc., is carried out with an inorganic ultraviolet absorber
      (titanium dioxide) deposit. We obtained an induced absorption contrast enhanced
      by a factor of 4.0, conferring enough sensitivity to detect monolayers of DNA or
      proteins. Experimental results on an Escherichia coli histidine-tagged methionyl
      tRNA synthetase protein before and after complexation with an anti-polyHis
      specific antibody validate our biosensing technique. This label-free optical
      method may be helpful in controlling biochip coatings, and subsequent biological
      coupling at the surface of a biochip.

PMID- 18823767
TI  - The role of H2O2 outer diffusion on the performance of implantable glucose
      sensors.
AB  - The performance of an implantable glucose sensor is strongly dependent on the
      ability of their outer membrane to govern the diffusion of the various
      participating species. In this contribution, using a series of layer-by-layer
      (LBL) assembled outer membranes, the role of outwards of H(2)O(2) diffusion
      through the outer membrane of glucose sensors has been correlated to sensor
      sensitivity. Glucose sensors with highly permeable humic acids/ferric cations
      (HAs/Fe(3+)) outer membranes displayed a combination of lower sensitivities and
      better linearities when compared with sensors coated with lesser permeable outer
      membranes (namely HAs/poly(diallyldimethylammonium chloride) (PDDA) and
      poly(styrene sulfonate) (PSS)/PDDA). On the basis of a comprehensive evaluation
      of the oxygen dependence of these sensors in conjunction with the permeability of
      H(2)O(2) through these membranes, it was concluded that the outer diffusion of
      H(2)O(2) is crucial to attain optimized sensor performance. This finding has
      important implications to the design of various bio-sensing elements employing
      perm-selective membranes.

PMID- 18823768
TI  - Electrically active polyaniline coated magnetic (EAPM) nanoparticle as novel
      transducer in biosensor for detection of Bacillus anthracis spores in food
      samples.
AB  - Electrically active polyaniline coated magnetic (EAPM) nanoparticle-based
      biosensor has been developed for the detection of Bacillus anthracis endospores
      in contaminated food samples. The 100 nm-diameter EAPM nanoparticles are
      synthesized from aniline monomer (made electrically active by acid doping)
      coating the surface of gamma iron oxide cores. The magnetic, electrical, and
      structural characteristics of the synthesized EAPM nanoparticles have been
      studied using superconducting quantum interference device (SQUID), four-point
      probe, and transmission electron microscopy (TEM). Room temperature hysteresis of
      the synthesized nanoparticles shows a saturation magnetization value of 44.1
      emu/g. The EAPM nanoparticles are biologically modified to act as an
      immunomagnetic concentrator of B. anthracis spores from lettuce, ground beef and
      whole milk samples and are directly applied to a direct-charge transfer
      biosensor. The detection mechanism of the biosensor depends on the capillary flow
      of the captured spores on the biosensor surface along with direct-charge transfer
      across the EAPM nanoparticles. Experimental results indicate that the biosensor
      is able to detect B. anthracis spores at concentrations as low as 4.2 x
      10(2)spores/ml from the samples. The EAPM-based biosensor detection system is
      fast and reliable with a total detection time of 16 min.

PMID- 18823769
TI  - Early determination of cystic fibrosis by electrochemical chloride quantification
      in sweat.
AB  - A novel and rapid approach to quantify chloride concentration in sweat for early
      detection of cystic fibrosis (CF) is shown in this work. Disposable screen
      printed sensor (SPS) devices capable to induce sweat and measure the chloride
      concentration are presented. Pilocarpine, which was forced into de skin by means
      of iontophoresis, has been used to stimulate the sweat glands. Chloride
      concentration has been directly measured on the skin by potentiometry. The
      performance of the devices has been tested in synthetic samples, obtaining good
      agreement with the Nernst equation. Sensors reproducibility has been analyzed in
      terms of residual standard deviation (RSD), obtaining a value of 8% (n=6 and
      alpha=0.05). Finally, the application of these sensors in several volunteers has
      been carried out. The results were compared with the method generally used in
      hospitals, obtaining deviations minor than 8%.

PMID- 18823770
TI  - Sensitive detection of cysteine based on fluorescent silver clusters.
AB  - In this work, we report the application of novel, water-soluble fluorescent Ag
      clusters in fluorescent sensors for detecting cysteine, an important biological
      analyte. The fluorescence of poly(methacrylic acid) (PMAA)-templated Ag clusters
      was found to be quenched effectively by cysteine, but not when the other alpha
      amino acids were present. By virtue of the specific response, a new, simple, and
      sensitive fluorescent method for detecting cysteine has been developed based on
      Ag clusters. The present assay allows for the selective determination of cysteine
      in the range of 2.5 x 10(-8) to 6.0 x 10(-6)M with a detection limit of 20 nM at
      a signal-to-noise ratio of 3. Based on the absorption and fluorescence studies,
      we suggested that cysteine quenched the emission by the thiol-adsorption
      accelerated oxidation of the emissive Ag clusters. The present study shows a
      promising step toward the application of silver clusters, a new class of
      attractive fluorescence probes.

PMID- 18823771
TI  - Bienzyme system for the biocatalyzed deposition of polyaniline templated by
      multiwalled carbon nanotubes: a biosensor design.
AB  - A novel method based on covalent attachment of two enzymes, glucose oxidase (GOD)
      and horseradish peroxide (HRP), onto carboxylic-derived multiwalled carbon
      nanotubes (MWNTs) for the deposition of electroactive polyaniline (PANI) under
      ambient conditions is described. Ultraviolet-visible spectroscopy, Fourier
      transform infrared (FTIR) spectroscopy, and transmission electron microscopy were
      used to characterize the assembling of bienzyme and the morphology of PANI|MWNTs.
      Under the bienzyme biocatalytic condition, a head-to-tail structure of PANI
      templated by MWNTs was formed. The voltammetric characteristics of the resulting
      biosensor were investigated by cyclic voltammetry in the presence of glucose. The
      current response of PANI was linearly related to glucose concentration between
      0.05 and 12.0mM with a correlation coefficient of 0.994. The synergistic
      performance of bienzyme, highly efficient polymerization, and templated
      deposition provide a general platform for the synthesis of nanowires and
      nanocircuits, the construction of bioelectronic devices, and the design of novel
      biosensors.

PMID- 18823772
TI  - Highly sensitive and selective oligonucleotide sensor for sickle cell disease
      gene using photon upconverting nanoparticles.
AB  - We report the design of an oligonucleotide sensor for the detection of point
      mutation associated with sickle cell disease. The sensor was based on
      luminescence resonance energy transfer between a donor and an acceptor. Photon
      upconverting nanoparticles (NaYF(4) doped with Yb(3+) and Er(3+)) were used as
      the donor and a conventional fluorophore, N,N,N',N'-tetramethyl-6
      carboxyrhodamine (TAMRA), as the acceptor. The sensor could detect the perfectly
      matched target, in the background of the mismatched target or other
      oligonucleotides of random sequences. The detection limit of this sensor towards
      perfectly matched target was calculated to be 120 femtomoles, with no
      photobleaching. Oligonucleotide sensors of such design demonstrate high
      sensitivity and specificity.

PMID- 18823773
TI  - Localized surface plasmon coupled fluorescence fiber-optic biosensor for alpha
      fetoprotein detection in human serum.
AB  - In this study, we demonstrated that the fiber-optic biosensor based on localized
      surface plasmon coupled fluorescence (LSPCF) is capable of detecting alpha
      fetoprotein (AFP) in human serum. The sensitivity of LSPCF fiber-optic biosensor
      is not only enhanced but also the specific selectivity is improved since the
      fluorophores are excited by the localized surface plasmon with high efficiency.
      Experimentally, this fiber-optic biosensor is able to detect AFP concentration in
      phosphate buffered saline (PBS) solution from 0.1ng/mL to 100ng/mL whereas the
      linear relationship between the AFP concentrations and the fluorescence signals
      is shown. Furthermore, a linear response between the fluorescence signals and the
      concentrations of AFP in human serum from 2.33ng/mL to 143.74ng/mL is also
      obtained. As a result, the detection limit of the LSPCF fiber-optic biosensor on
      AFP detection is comparable with the conventional enzyme-linked immunosorbent
      assay (ELISA). Additionally, the LSPCF fiber-optic biosensor benefits on
      inexpensive, disposable and simpler optical geometry that can become a high
      efficient immunoassay comparable with the conventional ELISA and radioimmunoassay
      (RIA) clinically.

PMID- 18823774
TI  - A comparison of paracervical block with single-shot spinal for labour analgesia
      in multiparous women: a randomised controlled trial.
AB  - BACKGROUND: Epidural and spinal analgesia may be contraindicated or unavailable
      in labour. This randomised controlled study examined the suitability of
      paracervical block as an alternative method of labour analgesia. METHODS:
      Multiparous women in labour were randomised to receive either paracervical block
      or single-shot spinal analgesia. Pain was quantified using a numerical rating
      scale. Subsequent analgesia, progress of labour, and mode of delivery were noted.
      Fetal heart rate patterns were reviewed. Apgar scores and umbilical artery pH
      measurements were collected. Parturients' satisfaction and willingness to have
      the same method of labour analgesia again were recorded. RESULTS: 122 parturients
      were randomised with data available on 104. Median pain scores decreased
      significantly in both groups; this was greater with single-shot spinal analgesia
      (difference between means 2.7; 95% CI 1.9-3.5; P(g)<0.001). Parturients receiving
      paracervical block received subsequent analgesia more often (23/56 vs. 3/48,
      P<0.001). Progress of labour, instrumental delivery rates, detected abnormal
      decelerations in cardiotocography and neonatal outcome were similar between
      groups. Shivering (P<0.04) and pruritus (P<0.001) were more common with single
      shot spinal analgesia. Parturients in the paracervical block group were less
      satisfied (median 7.0, IQR 3.0-8.0 vs. median 9.0, IQR 8.0-10.0; P<0.001) and
      less willing (28/55 vs. 39/48, P=0.002) to have the same labour analgesia again.
      CONCLUSIONS: Paracervical block was less effective than single-shot spinal
      analgesia. Both methods were associated with a low incidence of fetal bradycardia
      but maternal side effects were more common with single-shot spinal analgesia.

PMID- 18823775
TI  - A systematic review of the use and validation of health-related quality of life
      instruments in older cancer patients.
AB  - AIM: The aim of this paper is to systematically review the use and validation of
      HRQOL instruments in older cancer patients. METHOD: A systematic review of 5
      databases and 3 research registers identified studies reporting the use and
      validation of HRQOL instruments in cancer patients aged over 65 years from 1995
      to mid 2007. RESULTS: Thirty-one studies reported the use of HRQOL measures in
      older people, using a range of generic and disease-specific instruments. Little
      work was reported in patients aged over 80 years. All studies exhibited
      methodological limitations. Fourteen studies were identified with variable
      evidence on the psychometric properties and clinical usefulness of identified
      instruments. CONCLUSION: Our review identified that the development, validation
      and use of HRQOL instruments often ignore the specific needs of older people.
      This review highlights the need for a HRQOL instrument specifically designed to
      capture the issues and concerns most relevant to older cancer patients.

PMID- 18823776
TI  - Effects of selenium on arsenic uptake in arsenic hyperaccumulator Pteris vittata
      L.
AB  - Selenium (Se) is a non-metallic element, which has the capability to increase the
      antioxidative capacity and stress tolerance of plants to heavy metals. Plants
      vary considerably in their physiological response to Se. The reported research
      investigated the effects of Se on arsenic (As) uptake by As hyperaccumulator
      Pteris vittata L. and determined possible mechanisms of interaction. Pteris
      vittata plants were exposed hydroponically to 0, 150 or 300 microM of
      Na(2)HAsO(4) in the presence of 0, 5 or 10 microM of Na(2)SeO(4) for 5 or 10d.
      Application of 5 microM Se enhanced As concentration by P. vittata fronds by 7
      45%. At 5 microM, Se acted as an antioxidant, inhibiting lipid peroxidation
      (reduced by 26-42% in the fronds) via increased levels of thiols and glutathione
      (increased by 24% in the fronds). The results suggest that Se is either an
      antioxidant or it activates plant protective mechanisms, thereby alleviating
      oxidative stress and improving arsenic uptake in P. vittata.

PMID- 18823777
TI  - Development of mitochondria-targeted derivatives of resveratrol.
AB  - To target natural polyphenols to the subcellular site where their redox
      properties might be exploited at best, that is, mitochondria, we have synthesised
      new proof-of-principle derivatives by linking resveratrol (3,4',5-trihydroxy
      trans-stilbene) to the membrane-permeable lipophilic triphenylphosphonium cation.
      The new compounds, (4-triphenylphosphoniumbutyl)-4'-O-resveratrol iodide and its
      bis-acetylated derivative, the latter intended to provide transient protection
      against metabolic conjugation, accumulate into energized mitochondria as expected
      and are cytotoxic for fast-growing but not for slower-growing cells. They provide
      a powerful potential tool to intervene on mitochondrial and cellular redox
      processes of pathophysiological relevance.

PMID- 18823778
TI  - Development of bestatin-based activity-based probes for metallo-aminopeptidases.
AB  - A novel set of activity-based probes (ABPs) for functionally profiling metallo
      aminopeptidases was synthesized based on the bestatin inhibitor scaffold, the
      first synthesis of bestatin analogues using solid-phase techniques. These ABPs
      were shown to label metallo-aminopeptidases, using both a biotin and a
      fluorophore reporter, in an activity-dependent manner. This probe class was also
      shown to be amenable to 'click' chemistry labeling for possible use in live
      cells. Finally, we demonstrate that the ABPs are able to label an aminopeptidase
      in a complex proteome. Thus, these bestatin-based probes should have wide utility
      to functionally profile aminopeptidases in many biological systems.

PMID- 18823779
TI  - 5-Aminomethyl-1H-benzimidazoles as orally active inhibitors of inducible T-cell
      kinase (Itk).
AB  - A series of novel 5-aminomethyl-1H-benzimidazole based inhibitors of Itk were
      prepared. Structure-activity relationships, selectivity and cell activity are
      reported for this series. Compound 2, a potent and selective antagonist of Itk,
      inhibited anti-CD3 antibody induced IL-2 production in vivo in mice.

PMID- 18823780
TI  - Statin use and the risk of Parkinson disease: a nested case control study.
AB  - Using the British Columbia Linked Health Databases, we explored the association
      between the use of statin drugs and the risk of developing Parkinson disease
      (PD). We followed a cohort of older adults in the Province of British Columbia
      from 1997 to 2003. Using a study design of nested case control (case-control
      study within a cohort), the relative risk of developing PD for statin users was
      0.94 (0.82-1.09). Our study did not show a statistically significant effect on
      the risk of PD with statin use.

PMID- 18823781
TI  - A case of compression fracture of medial tibial plateau and medial femoral
      condyle combined with posterior cruciate ligament and posterolateral corner
      injury.
AB  - We report a case of compression fracture of anterior margin of medial tibial
      plateau and medial femoral condyle combined with the posterior cruciate ligament
      and posterolateral corner disruption. A thirty-seven-year old male had undergone
      the left knee injury 6 months before. The physical examination revealed positive
      posterior drawer test and tibial dial test, which evidenced the posterior
      cruciate ligament and posterolateral corner insufficiency. The plain lateral knee
      radiographs showed a marginal fracture of the anteromedial tibial plateau and a
      dimpling on the adjacent part of the medial femoral condyle. On arthroscopy,
      there were no gross tear of the cruciates, but the posterolateral capsule
      disclosed stigmata of stretching injury with multiple petechiae and scarring. The
      compression fracture on the anteromedial side and the stretching injury on the
      posterolateral side altogether support the mechanism of hyperextension pivoting
      on the anteromedial side of the knee joint. A small bony lesion around the knee
      joint should be inspected rigorously with an assumed mechanism of injury for it
      may herald major ligamentous injury.

PMID- 18823782
TI  - Synthesis and recovery of high bioactive phenolics from table-olive brine process
      wastewater.
AB  - The generated wastewater of table-olive brine processing contains a high amount
      of polyphenols which are endowed with interesting biological activities. The
      ethyl acetate extract (EAE) of such wastewater shows high hydroxytyrosol (HT) and
      tyrosol concentrations of 690 and 98 mg g(-1) dry weight extract, respectively.
      Phenolic compounds analysis was performed by gas chromatography-mass spectrometry
      (GC-MS). The antioxidant activity was evaluated by the scavenging effect on DPPH
      (2,2-diphenyl-1-picrylhydrazyl) and ABTS (2,2'-Azinobis[3-ethylbenzothiazoline-6
      sulfonate] radicals. Total polyphenol content was estimated with the Folin
      Ciocalteu assay. Hydroxytyrosol has DPPH and ABTS radicals scavenging activities
      higher than 2,6-di-tert-butyl-hydroxytoluene (BHT), while triacetylated
      hydroxytyrosol (triAcHT) was devoid of any antioxidant activity. The assessment
      of these antioxidant compounds in biological systems was carried out by the
      determination of their in vitro cytotoxicity against two different human cancer
      cell lines (HeLa and DG75) and normal peripheral blood lymphocytes (PBL) using
      the MTT assay. The 50% cytotoxic concentrations were ranged between 27 and 210
      microg mL(-1) for Hela and DG75. At the same concentration range, the EAE and the
      pure HT and triAcHT exhibited an insignificant cytotoxicity against PBL.
      Incubation of HeLa and DG75 cells with non-cytotoxic concentrations of EAE, HT or
      triAcHT resulted in a remarkable protection from the oxidative stress induced by
      Fe(2+). The antimicrobial activity evaluated by the broth dilution NCCL method
      using Gram-positive (Staphylococcus aureus, Bacillus subtilis) and Gram-negative
      (Pseudomonas aeruginosa, Escherichia coli, Salmonella enterica) bacteria and
      (Candida albicans, Aspergillus niger) fungi showed a broad spectrum bactericidal
      and fungicidal effect of table-olives-EAE, HT and triAcHT. The MICs vary from 125
      to 500 microg mL(-1) for bacteria and from 500 to 2000 microg mL(-1) for fungi.

PMID- 18823783
TI  - Spectroscopic studies on the formation and thermal stability of DNA triplexes
      with a benzoannulated delta-carboline-oligonucleotide conjugate.
AB  - A benzoannulated delta-carboline with a phenyl substituent has been covalently
      tethered to the 3'-end of a triplex-forming oligonucleotide and its ability to
      bind and stabilize DNA triple helices has been examined by various spectroscopic
      methods. UV thermal melting experiments were conducted with different hairpin
      duplexes and with a complementary single-stranded oligonucleotide as targets for
      the conjugate. The delta-carboline ligand preferentially binds triplexes over
      duplexes and leads to a temperature increase of the triplex-to-duplex transition
      by up to 23 degrees C. The results obtained from UV, CD and fluorescence
      measurements suggest that the delta-carboline ligand exhibits specific
      interactions with a triplex and favors binding by intercalation at the triplex
      duplex junction.

PMID- 18823784
TI  - Structure-activity relationship studies of imidazo[1,2-c]pyrimidine derivatives
      as potent and orally effective Syk family kinases inhibitors.
AB  - Spleen tyrosine kinase (Syk) and zeta-associated protein kinase of 70k Da (ZAP
      70) are members of the Syk family and non-receptor-type protein tyrosine kinases,
      which play crucial roles in B- and T-cell activation. Therefore, a Syk family
      tyrosine kinases inhibitor would be a useful therapeutic agent for the treatment
      of various allergic disorders and autoimmune diseases. Previously, we reported
      that 1,2,4-triazolo[4,3-c]pyrimidine derivative 1 and 1,2,4-triazolo[1,5
      c]pyrimidine derivative 2 showed strong inhibitory activities against Syk family
      kinases. These compounds also exhibited high-level suppression of IL-2 in
      cellular assays. However, their oral efficacies were poor in a mouse model of IL
      2 production. To improve oral effectiveness, we investigated a new series of Syk
      family kinases inhibitors. We found that imidazo[1,2-c]pyrimidine derivatives
      potently inhibited the Syk family kinases. Among these agents, compound 9f not
      only showed strong inhibitory activities against Syk and ZAP-70 kinases in vitro,
      but its oral administration resulted in the in vivo suppression of both the
      passive cutaneous anaphylaxis reaction and Concanavalin A-induced IL-2 production
      in a mouse model.

PMID- 18823785
TI  - Design and synthesis of dinucleotide 5'-triphosphates with expanded
      functionality.
AB  - We propose the new approach to the synthesis of 5'-triphosphate derivatives of
      natural and modified dinucleotides with expanded functionality. Our strategy
      includes the combination of the solution phase synthesis of necessary dimers
      using the wide range of nucleic acids chemistry methods and the subsequent
      introduction of the triphosphate residue. A number of the new potential
      substrates for the template dependent synthesis of nucleic acids with expanded
      functionality are obtained, namely, 5'-triphosphates of dinucleotides containing
      the functionally active groups in heterocyclic bases, in carbohydrate-phosphate
      backbone, and the groups mimicking the residues of natural amino acids. The
      abilities of the proposed synthetic route are also demonstrated by the synthesis
      of 5'-triphosphates of dinucleotides with modified carbohydrate-phosphate
      backbone.

PMID- 18823786
TI  - Aldehydic components of cinnamon bark extract suppresses RANKL-induced
      osteoclastogenesis through NFATc1 downregulation.
AB  - Several major bone diseases are directly attributable to bone loss, including
      osteoporosis, bone metastasis, and rheumatoid arthritis. The nuclear factor of
      activated T cell 1 (NFATc1), a transcription factor, has recently been shown to
      play an essential role in osteoclastogenesis. In this study, we found that of
      several herbs, Cinnamomum zeylanicum (C. zeylanicum) exhibited the strong
      inhibitory effects on osteoclastogenesis and that its mechanism of action
      involves the suppression of NFATc1-mediated signal transduction. C. zeylanicum
      dose-dependently inhibited osteoclast-like cell formation at concentrations of
      12.5-50 microg/ml without affecting cell viability. Resorption pit assays have
      shown that C. zeylanicum also inhibits the bone-resorbing activity of mature
      osteoclasts. Treatment with C. zeylanicum inhibited the receptor activator of
      nuclear factor-kappaB ligand (RANKL)-induced NFATc1 and c-fos expression.
      Additionally, C. zeylanicum moderately inhibited phosphorylation of IkappaB
      alpha, suggesting that the c-fos/NFATc1 pathway, rather than the nuclear factor
      kappaB (NF-kappaB) pathway, is the primary target of C. zeylanicum during RANKL
      induced osteoclastogenesis. Using an HPLC-DAD system, we identified three major
      peaks for four characteristic components in the C. zeylanicum extract and
      identified an unknown peak as 2-methoxycinnamaldehyde via HPLC and a 2D-COSY (1)H
      NMR study. We identified cinnamaldehyde and 2-methoxycinnamaldehyde as active
      components reducing osteoclast-like cell formation and inhibiting NFATc1
      expression. Notably, in a resorption pit assay, 2-methoxycinnamaldehyde exhibited
      remarkable inhibition rates of 95% at 2 microM on bone resorption. In summary,
      this study points to the conclusion that C. zeylanicum inhibits RANKL-induced
      osteoclastogenesis. This finding raises prospects for the development of a novel
      approach in the treatment of osteopenic disease.

PMID- 18823787
TI  - Histological and histochemical effects after occlusion alteration in suprahyoid
      muscles.
AB  - This study verified the effect of unilateral teeth extraction on the suprahyoid
      muscles in gerbils (Meriones unguiculatus). Ten adult male gerbils weighing about
      50g had induced occlusal alterations by upper molar teeth extraction on the left
      side while the other ten animals were only subjected to surgical stress, control
      group. After 60 days, animals of both groups, experimental and control had the
      suprahyoid muscles removed and processed for histological and histochemical
      (adenosine triphosphatase (ATPase), nicotine adenine dinucleotide tetrazolium
      reductase (NADH-TR) and succinate dehydrogenase (SDH)) purposes. The fiber type
      area was estimated in % according to Weibel method (point-counting method) using
      a test-system. The myosinic ATPase pH 4.7 activity in the control group of the
      digastric, milohyoid and geniohyoid muscles presented a small area of type I
      fiber and a larger area of type IIa fibers; in the experimental group,
      significant contractile capacity alteration was not observed. Samples of the
      digastric, milohyoid and geniohyoid muscles, after SDH activity, showed a small
      area with high metabolic activity fibers, and a large area with intermediary and
      low metabolic activity fibers in the control group. The milohyoid muscle of the
      experimental group presented low metabolic fibers in a reduced area, in both
      sides, however without significant difference. In the experimental group, high
      metabolic fibers were observed on the left side in a reduced area in the
      geniohyoid muscle, but without statistical significance. Thus, the geniohyoid
      muscle did not change the metabolic activity after occlusal alteration. In
      conclusion, 60 days of unilateral malocclusion induced was able to alter the
      fibers oxidative activity of the suprahyoid muscles, however, it does not affect
      the contractile property of the fibers. The digastric muscle has adequate fibers
      to produce fast contraction and able to resist to fatigue in intermediate
      degrees, but became more fatigable after unilateral exodontia.

PMID- 18823788
TI  - Monte-Carlo simulations of elastically backscattered neutrons from hidden
      explosives using three different neutron sources.
AB  - Calculations of elastically backscattered (EBS) neutrons from hidden explosives
      buried in soil were performed using Monte-Carlo N-particle transport code MCNP5.
      Three different neutron sources were used in the study. The study re-examines the
      performance of the neutron backscattering methods in providing identification of
      hidden explosives through their chemical composition. The EBS neutron energy
      spectra of fast and slow neutrons of the major constituent elements in soil and
      an explosive material in form of TNT have shown definite structures that can be
      used for the identification of a buried landmine.

PMID- 18823789
TI  - Rupture of the left atrial 'basal' appendage due to blunt trauma in an elderly
      patient.
AB  - Blunt traumatic cardiac rupture is associated with a high mortality rate. Motor
      vehicle accidents account for most cardiac ruptures, but crush injury is
      relatively rare. We describe a case of a 77-year-old man who had the left atrial
      'basal' appendage ruptured through blunt trauma due to a fall. He was surgically
      treated and recovered without complication.

PMID- 18823790
TI  - Vascular ring and coarctation of the aorta associated with oesophageal atresia.

PMID- 18823791
TI  - Aberrant subclavian artery as origin of aortic dissection.

PMID- 18823792
TI  - The epidemiologic transition model: accomplishments and challenges.

PMID- 18823793
TI  - Epidemiology: key to translational, team, and transdisciplinary science.

PMID- 18823794
TI  - Crisscross-configured dual stent placement for trisectoral drainage in patients
      with advanced biliary hilar malignancies.
AB  - PURPOSE: To evaluate technical success and clinical efficacy of crisscross
      configured dual biliary stent implantation in patients with a biliary hilar tumor
      extending beyond the segmental ducts. MATERIALS AND METHODS: Between January 2002
      and December 2006, two metallic stents were placed crossing each other in a
      hepatic hilum in 42 patients. One stent was placed between one right sectoral
      duct and the left hepatic duct and the other was placed between another right
      sectoral duct and the common bile duct. The patients ranged in age from 36 to 83
      years (mean, 63.3 y) and included 26 men and 16 women. Technical success,
      clinical success, complications, and long-term results were analyzed by
      retrospective review. RESULTS: Stent placement was performed through two right
      accesses (n = 30), one right and one left access (n = 3), or two right accesses
      and one left access (n = 6). Successful "trisectoral" drainage was obtained with
      two stents in 41 patients (98%). In one case of initial technical failure, an
      additional stent was needed to connect the two previously placed stents. Clinical
      success was obtained in 34 of the remaining 36 patients (92%). No procedure
      related major complication was observed. The median primary stent patency time
      was 187 days and the median patient survival time was 247 days. CONCLUSIONS:
      Crisscross-configured dual stent implantation is a feasible, safe, and effective
      method to maximize hepatic drainage with a minimal number of stents in patients
      with advanced biliary hilar malignancy.

PMID- 18823795
TI  - Comparative study of four different spherical embolic particles in an animal
      model: a morphologic and histologic evaluation.
AB  - PURPOSE: To perform a study in a porcine model comparing four different spherical
      embolic particles in terms of postembolization patency, deformation, and
      potential for recanalization, with a focus on a relatively new agent--HepaSphere.
      MATERIALS AND METHODS: Partial embolization of both kidneys was performed in 18
      pigs. Nine animals were sacrificed at 48 hours and nine at 4 weeks. In the same
      animal, the right kidney was embolized with HepaSphere particles ("dry" size, 50
      100 microm; presumed final size, 200-300 microm), and the left kidney was
      alternatively embolized with EmboSphere (100-300 microm), Contour (150-350
      microm), or Bead Block (150-350 microm) particles. The authors analyzed the size,
      deformation, and number of particles in each vessel, their morphologic
      characteristics, and recanalization. RESULTS: Particle sizes and deformation
      (1,096 particles) were as follows: HepaSphere, 225.3 microm +/- 67 and 26% +/-
      19.7, respectively; EmboSphere, 132.9 microm +/- 36 and 18.1% +/- 14.2; Bead
      Block, 108.1 microm +/- 38 and 16.5% +/- 13.9; and Contour, 240.8 microm +/- 135
      and 55.5% +/- 33. HepaSphere and Bead Block particles were distally located, and
      EmboSphere and Contour particles were located more proximally. EmboSphere and
      Bead Block particles were round, HepaSphere particles were round and/or ovoid,
      and Contour particles had an amorphous aspect. EmboSphere particles had a higher
      tendency to aggregate. No recanalization was seen with HepaSphere particles, and
      variable recanalization was observed with the others. CONCLUSIONS: Despite
      similar initial morphologic characteristics, the performance of the agents tested
      in this study differed in terms of final size, shape, deformation, and luminal
      recanalization. These differences have potential clinical relevance, and the
      knowledge of the differing embolic performance may be helpful in choosing agents
      for specific therapeutic purposes.

PMID- 18823796
TI  - The lymphocele PILL: a case report of percutaneous imaging-guided lymphatic
      ligation for the treatment of postsurgical lymph collections.
AB  - Lymphoceles occur after surgical interventions in areas with an extensive
      lymphatic network due to injury to the large lymphatic vessels. Recurrent
      lymphoceles are treated percutaneously by using sclerotherapy, with surgery
      reserved for cases of failed sclerotherapy. In this case report, the authors
      describe a minimally invasive technique using lymphangiography and percutaneous
      imaging-guided lymphatic ligation of the feeding lymphatic vessel of a persistent
      lymphocele refractory to the sclerotherapy.

PMID- 18823797
TI  - Bidirectionally adjustable TIPS reduction by parallel stent and stent-graft
      deployment.
AB  - Excessive shunting through transjugular intrahepatic portosystemic shunts (TIPS)
      can cause life-threatening hepatic encephalopathy and insufficiency. Intentional
      reduction of flow may be effective but difficult to control. The present report
      describes refinements of the parallel stent/stent-graft technique of flow
      reduction that is adjustable in either direction. Six patients underwent TIPS
      reduction with varying stent positioning and a variety of commercial products.
      Flow was adjusted by iterative balloon dilatation of the stent and stent-graft,
      resulting in a mean gradient increase of 8 mm Hg. All cases were technically
      successful, but 1-year survival was seen in only the patient who underwent liver
      transplantation.

PMID- 18823798
TI  - Discrete subaortic membranes in adults--a clinicopathological analysis.
AB  - INTRODUCTION: A discrete subaortic membrane (DSM) is one of the causes of
      subaortic stenosis in children. The incidence, characteristics, and the
      therapeutic options for such membranes in adults have not been well documented.
      This report documents the clinical and pathological features of DSM in adults.
      METHODS: DSMs, surgically excised over a 10-year period in a large adult tertiary
      care center, were reviewed with regard to the age and gender of the patients,
      clinical findings, and the morphological features. RESULTS: Among the 19 adults,
      there were six males and 13 females, with age ranging from 26 to 75 years. The
      patients most often presented with dyspnea, fatigability, and palpitation for 3
      months to 2 years. Four patients (21%) had other congenital heart disease in
      association with the DSM; in the rest, the membranes were isolated occurrences
      (79%). A cardiac murmur or the presence of membranes had been noted in childhood
      in four patients. Tissue growths over the ventricular surface of the anterior
      mitral leaflet were seen in 18 cases. Irrespective of the gross appearance, the
      stenosing lesions exhibited five tissue layers, beginning from the luminal
      aspect, endothelium, acid mucopolysaccharide-rich subendothelial layer, collagen
      rich fibrous layer, fibroelastotic layer, and a smooth muscle layer. Twelve
      patients (63%) had aortic regurgitation, which necessitated repair or replacement
      in seven. Septal myectomy resulted in conduction abnormalities in nine.
      CONCLUSIONS: The study describes the occurrence of DSM in adults. It is important
      to remember that it can occur following a repair of underlying congenital heart
      disease.

PMID- 18823799
TI  - A multicenter, prospective, randomized, controlled trial of open reduction-
      internal fixation versus total elbow arthroplasty for displaced intra-articular
      distal humeral fractures in elderly patients.
AB  - We conducted a prospective, randomized, controlled trial to compare functional
      outcomes, complications, and reoperation rates in elderly patients with displaced
      intra-articular, distal humeral fractures treated with open reduction-internal
      fixation (ORIF) or primary semiconstrained total elbow arthroplasty (TEA). Forty
      two patients were randomized by sealed envelope. Inclusion criteria were age
      greater than 65 years; displaced, comminuted, intra-articular fractures of the
      distal humerus (Orthopaedic Trauma Association type 13C); and closed or Gustilo
      grade I open fractures treated within 12 hours of injury. Both ORIF and TEA were
      performed following a standardized protocol. The Mayo Elbow Performance Score
      (MEPS) and Disabilities of the Arm, Shoulder and Hand (DASH) score were
      determined at 6 weeks, 3 months, 6 months, 12 months, and 2 years. Complication
      type, duration, management, and treatment requiring reoperation were recorded. An
      intention-to-treat analysis and an on-treatment analysis were conducted to
      address patients randomized to ORIF but converted to TEA intraoperatively. Twenty
      one patients were randomized to each treatment group. Two died before follow-up
      and were excluded from the study. Five patients randomized to ORIF were converted
      to TEA intraoperatively because of extensive comminution and inability to obtain
      fixation stable enough to allow early range of motion. This resulted in 15
      patients (3 men and 12 women) with a mean age of 77 years in the ORIF group and
      25 patients (2 men and 23 women) with a mean age of 78 years in the TEA group.
      Baseline demographics for mechanism, classification, comorbidities, fracture
      type, activity level, and ipsilateral injuries were similar between the 2 groups.
      Operative time averaged 32 minutes less in the TEA group (P = .001). Patients who
      underwent TEA had significantly better MEPSs at 3 months (83 vs 65, P = .01), 6
      months (86 vs 68, P = .003), 12 months (88 vs 72, P = .007), and 2 years (86 vs
      73, P = .015) compared with the ORIF group. Patients who underwent TEA had
      significantly better DASH scores at 6 weeks (43 vs 77, P = .02) and 6 months (31
      vs 50, P = .01) but not at 12 months (32 vs 47, P = .1) or 2 years (34 vs 38, P =
      .6). The mean flexion-extension arc was 107 degrees (range, 42 degrees -145
      degrees) in the TEA group and 95 degrees (range, 30 degrees -140 degrees) in the
      ORIF group (P = .19). Reoperation rates for TEA (3/25 [12%]) and ORIF (4/15
      [27%]) were not statistically different (P = .2). TEA for the treatment of
      comminuted intra-articular distal humeral fractures resulted in more predictable
      and improved 2-year functional outcomes compared with ORIF, based on the MEPS.
      DASH scores were better in the TEA group in the short term but were not
      statistically different at 2 years' follow-up. TEA may result in decreased
      reoperation rates, considering that 25% of fractures randomized to ORIF were not
      amenable to internal fixation. TEA is a preferred alternative for ORIF in elderly
      patients with complex distal humeral fractures that are not amenable to stable
      fixation. Elderly patients have an increased baseline DASH score and appear to
      accommodate to objective limitations in function with time.

PMID- 18823800
TI  - In vitro and finite element analysis of a novel rotator cuff fixation technique.
AB  - The purpose of this investigation was to assess the biomechanic strength and
      stress dispersion at the repair site of surface-holding repair techniques for
      rotator cuff repair compared to the double-row technique. Eighteen bovine
      infraspinatus tendons were repaired using 3 different repair techniques: double
      row repair, surface-holding repair with transosseous sutures, and surface-holding
      repair with knotless anchors. Biomechanical testing and two-dimensional finite
      element analysis were performed. The surface-holding repair with transosseous
      sutures provided 87.9% more stiffness than the double-row repair. The number of
      tendon-suture site failures of the surface-holding repair with transosseous
      sutures was smaller than the other 2 techniques. The finite element analysis
      showed that the surface-holding repair model had a more dispersing stress pattern
      compared to a double-row repair model. It suggests that these repair techniques
      can prevent high stress concentration compared to the double-row repair.

PMID- 18823801
TI  - Factors associated with health-related quality of life, anxiety and depression
      among young adults with epilepsy and mild cognitive impairments in short-term
      residential care.
AB  - INTRODUCTION: This study examined associations of health-related quality of life
      (HRQOL), anxiety, and depression with medical and psychosocial variables.
      Participants were young adults with epilepsy and additional mild cognitive
      impairments in short-term residential care of the Bethel Institute, Germany.
      METHODS: Thirty-six individuals were interviewed using the Quality of Life in
      Epilepsy Inventory 31 (QOLIE-31), the Hospital Anxiety and Depression Scale
      (HADS) and the neuroticism scale of the Neo-Five-Factor Inventory (NEO-FFI).
      Medical as well as socio-demographic data were assembled from client files.
      RESULTS: Regression analyses revealed neuroticism as the strongest predictor of
      HRQOL, anxiety and depression. The only variables that additionally explained a
      substantial proportion of variance counting for 6-10% in the three criteria were
      age at epilepsy onset and sex: epilepsy onset after the age of 10 years was
      associated with lower HRQOL and higher anxiety, men suffered from more depression
      than women. DISCUSSION: Neuroticism as a personality disposition seems to be most
      influential on HRQOL and anxiety in people with epilepsy and mild cognitive
      impairment. The impact of sex and age at epilepsy onset on HRQOL, anxiety and
      depression of this epilepsy subpopulation should be further clarified.

PMID- 18823802
TI  - Focus laterality and interictal psychiatric disorder in temporal lobe epilepsy.
AB  - The current study was carried out in order to find the possible associations
      between foci laterality and kind of prevailed psychopathological disorder in
      patients with temporal lobe epilepsy (TLE). One hundred and ten patients with TLE
      (40 men and 70 women) were included into the study. Among all studied patients
      the left-focus activity was detected in 67 patients, right-sided foci-in 43
      patients. No relationships between chronology variables of epilepsy (age, age at
      epilepsy onset, epilepsy duration) and different subtypes of psychopathology in
      studied patients were revealed. Diagnosis of organic affective disorder was
      observed more frequently in patients with right-sided foci, while diagnosis of
      organic anxiety disorder-in patients with left-sided foci (chi(2)=7.0, p=0.0081;
      Fisher's exact test p=0.018). The comparison of dysphoric disorder with anxiety
      or affective disorder could not reveal any statistically significant association
      with focus laterality. Obtained results are discussed in terms of association
      between the different subtypes of studied psychiatric disorders and foci
      laterality in patients with TLE.

PMID- 18823803
TI  - Severe iron overload with a novel aminolevulinate synthase mutation and hepatitis
      C infection. A case report.
AB  - A 55 year old man with a history of chronic hepatitis C infection was found to
      have severe hemochromatosis: hepatic cirrhosis, cardiomyopathy, arrhythmia,
      hypogonadism, diabetes and bronzed skin color. After 50 phlebotomies, he
      underwent a combined heart and liver transplant. Genetic analyses identified a
      novel mutation in the iron responsive element of the ALAS2 gene. No mutations
      were found in other genes associated with adult or juvenile hemochromatosis
      including HFE, transferrin receptor-2 (TFR2), ferroportin (SLC40A1), hepcidin
      (HAMP) and hemojuvelin (HJV). We suggest that the ALAS2 mutation together with
      chronic hepatitis C infection may have caused the severe iron overload phenotype.

PMID- 18823804
TI  - Acquired isolated unilateral fourth nerve palsy after ventriculoperitoneal shunt
      surgery.
AB  - Ventriculoperitoneal shunt has been the surgical procedure of choice for many
      years for both communicating and noncommunicating hydrocephalus.(1) High failure
      rates and complications have been reported, despite major improvements in shunt
      technology(2); however, fourth (trochlear) nerve palsy has not been reported
      after this procedure. We describe 2 patients who developed a fourth nerve palsy
      after shunt surgery. Recovery was incomplete, and strabismus surgery was
      required.

PMID- 18823805
TI  - Quantitative optical coherence tomography findings in a 4-year-old boy with
      typical morning glory disk anomaly.
AB  - Morning glory disk anomaly (MGDA) is a congenital malformation of the optic disk
      that is usually unilateral. It has characteristic fundus findings, including
      enlarged optic disk opening and funnel-shaped excavation of the peripapillary
      fundus. Optical coherence tomography (OCT) with micrometer resolution and cross
      sectional imaging capabilities can provide detailed information about the
      structure of the living eye. Some reports have used OCT to demonstrate the
      structure of the disk in older patients with MGDA but, to our knowledge, no
      quantitative OCT report concerning a child with MGDA has been published
      previously.

PMID- 18823806
TI  - Methodological aspects of crossover and maximum fat-oxidation rate point
      determination.
AB  - AIM: Indirect calorimetry during exercise provides two metabolic indices of
      substrate oxidation balance: the crossover point (COP) and maximum fat oxidation
      rate (LIPOXmax). We aimed to study the effects of the analytical device, protocol
      type and ventilatory response on variability of these indices, and the
      relationship with lactate and ventilation thresholds. METHODS: After maximum
      exercise testing, 14 relatively fit subjects (aged 32+/-10 years; nine men, five
      women) performed three submaximum graded tests: one was based on a theoretical
      maximum power (tMAP) reference; and two were based on the true maximum aerobic
      power (MAP). Gas exchange was measured concomitantly using a Douglas bag (D) and
      an ergospirometer (E). RESULTS: All metabolic indices were interpretable only
      when obtained by the D reference method and MAP protocol. Bland and Altman
      analysis showed overestimation of both indices with E versus D. Despite no mean
      differences between COP and LIPOXmax whether tMAP or MAP was used, the individual
      data clearly showed disagreement between the two protocols. Ventilation explained
      10-16% of the metabolic index variations. COP was correlated with ventilation
      (r=0.96, P<0.01) and the rate of increase in blood lactate (r=0.79, P<0.01), and
      LIPOXmax correlated with the ventilation threshold (r=0.95, P<0.01). CONCLUSION:
      This study shows that, in fit healthy subjects, the analytical device, reference
      used to build the protocol and ventilation responses affect metabolic indices. In
      this population, and particularly to obtain interpretable metabolic indices, we
      recommend a protocol based on the true MAP or one adapted to include the
      transition from fat to carbohydrate. The correlation between metabolic indices
      and lactate/ventilation thresholds suggests that shorter, classical maximum
      progressive exercise testing may be an alternative means of estimating these
      indices in relatively fit subjects. However, this needs to be confirmed in
      patients who have metabolic defects.

PMID- 18823807
TI  - Ultrasound of the peripheral nerves.
AB  - Peripheral nerves disorders are common in the rheumatologic practice and can
      mimic a variety of musculoskeletal diseases. Clinical evaluation remains the
      mainstay for diagnosing nerve disorders of the extremities. A careful history and
      an accurate physical examination lead in most patients to a high diagnostic
      suspicion. Nevertheless several imaging techniques are usually obtained to
      confirm the clinical data and in the preoperative workup. Although standard
      radiographs and computed tomography do not visualize the nerves directly, they
      can reveal the adjacent anatomic structures such as bones and joints and can add
      additional information that frequently is essential in the choice of adequate
      treatment. Magnetic resonance imaging and ultrasound show peripheral nerves
      directly and can reveal their size and internal structure. With the new
      developments in high resolution, electronic broadband transducers, ultrasound
      (US) is now considered an optimal imaging technique to evaluate the normal
      anatomy and disorders of peripheral nerves. Well recognized advantages of this
      technique in this field are: the possibility of realizing a dynamic examination
      and assessing long nerves segments in a short time; it is non-invasive and low
      cost. In addition US is better accepted by the patients. In this article we
      present a brief description of the normal and US anatomy of the peripheral nerves
      followed by a description of the US appearance of the most frequent disorders:
      entrapment neuropathies (EN), tumor and cystic lesions.

PMID- 18823808
TI  - Combined rotatory and lateral atlanto-axial subluxation in rheumatoid arthritis:
      a case report.

PMID- 18823809
TI  - [Clinical practice recommendations: what if doctors regained upper hand?].

PMID- 18823810
TI  - [Surgical management of pelvic organ prolapse in women: laparoscopic or vaginal
      sacrocolpopexy?].
AB  - OBJECTIVE: To compare the safety and the efficacy of the laparoscopic and vaginal
      technique for the surgical management of pelvic organ prolapse, with systematic
      support of the three compartments and prosthetic reinforcements. PATIENTS AND
      METHODS: Retrospective study of 154 patients presenting a stage 3 or 4 prolapse
      on one of the three compartments. Laparoscopic procedures were performed with
      subtotal hysterectomy, double synthetic prosthesis attached to promontory, and
      douglassectomy. Vaginal procedures were performed with vaginal hysterectomy,
      anterior colporrhaphy with a hammock using porcine skin collagen implant fixed by
      transobturator passages, unilateral sacral colpopexy and posterior colporrhaphy.
      Monitoring was performed at six months and then annually. RESULTS: The
      laparoscopic technique requires a more important operating time, but a shorter
      hospitalization. The discovery of three carcinoma reinforces the idea of the
      interest of uterine radical surgery in these patients. The tolerance of
      prostheses by laparoscopy is safe. The biological prostheses, introduced
      vaginally, offer the same advantages. The anatomical results in the medium term
      (30 months) seem more favorable to laparoscopy than transvaginal approach, as
      well as functional results but they still need to better evaluated. DISCUSSION
      AND CONCLUSION: The two techniques must coexist, ideally without competing with
      each other but rather complementarily, as the overall rate of recurrence,
      requiring additional procedure does not exceed 2%. It is therefore important that
      surgeons, who support prolapse, have a good comprehensive training of the
      laparoscopic and vaginal techniques.

PMID- 18823811
TI  - [Practical questions in case of maternal death].
AB  - Every year, in France, about 70 women die during their pregnancy or the delivery.
      Any maternal death during labour is a traumatic event for the medical team and
      the family. The medical team has to face many "new" problems. We try to identify
      all the problems which the medical team has to face in front of a maternal death
      and try to solve them by a medical literature and French laws review. The medical
      team often feels powerless when a maternal death occurs. This work was made to be
      a guideline.

PMID- 18823812
TI  - Assessment of cervical venous blood flow and the craniocervical venus valve using
      ultrasound sonography.
AB  - Severe congestion with petechiae and/or small hemorrhages over a wide area
      consisting of the subcutaneous and mucous level of the head and neck is observed
      in most cases of strangulation and positional asphyxial death. Congestion present
      above the strangulation mark is accepted as a vital reaction. Although the
      congestion results from a disturbance of cervical venous flow, only a few reports
      concerning a relationship between venous flow and posture were found in the
      literature. We assessed the physiological situation of cervical venous return and
      movement of the craniocervical venous valve for many types of valve with respect
      to posture using color-duplex ultrasound sonography (US). We measured the Doppler
      wave of cervical veins consisting of internal jugular vein (IJV), external
      jugular vein (EJV) and vertebral vein (VV) and the motion of IJV valves in three
      positions on a seat which could be manually moved through +90 degrees to -90. The
      diameter of IJVs and EJVs were thicker in a head-down position, moderate in a
      supine position and flat in a sitting position. The diameter of VVs was thick in
      a sitting position, moderate in supine position and unclear in an upside-down
      position because of difficulty in scanning owing to very slow velocity and deep
      lying position. The velocities were high in a sitting position, but very slow and
      intermittent in an upside-down position. The EJV which is markedly congested in
      some cardiac tamponade cases and drains mainly the facial superficial region is
      very important in legal medicine but has not often observed in previous reports.
      We confirmed that cervical venous return (IJV, EJV, VV) changes its route
      according to the posture. The motion of IJV valves was very complicated and
      varied in three positions, even after the Doppler wave and the motion of valve
      became stable. Asphyxia and strangulation should be studied taking the complex
      venous structure into consideration. We could not find any consistent explanation
      for venous valve motion and further studies on the valves are necessary to
      understand the venous reflux in some diseases in legal medicine.

PMID- 18823813
TI  - Plasma amantadine concentrations in patients with Parkinson's disease.
AB  - We determined plasma amantadine concentrations in patients with Parkinson's
      disease (PD) in daily clinical practice and investigated the relationship between
      plasma concentration and adverse reactions to clarify the safe therapeutic range.
      Seventy-eight consecutive PD patients on stable amantadine treatment were
      recruited. Plasma concentration of amantadine was measured 3h after the
      administration of morning amantadine dose. Serum creatinine was measured to
      estimate renal function. The mean daily dose of amantadine was 135.1+/
      62.3mg/day, and the mean plasma amantadine concentration was 812.5+/-839.5 ng/ml
      (range, 91-4400 ng/ml). Plasma amantadine concentration increased according to
      increasing renal dysfunction. Three patients exhibited adverse reactions, such as
      myoclonus, hallucinations, and delirium, and all of them showed plasma amantadine
      concentration >3000 ng/ml. None of the three cases had previously shown such side
      effects. PD patients who have not developed any psychiatric symptoms as adverse
      reactions to the treatment may develop myoclonus, hallucination, or delirium when
      the plasma concentration of amantadine exceeds 3000 ng/ml. It is therefore
      recommended to use amantadine at the plasma concentration of less than 3000 ng/ml
      in the treatment of Parkinson's disease, especially in elderly patients.

PMID- 18823814
TI  - 3D estimation of soft biological tissue deformation from radio-frequency
      ultrasound volume acquisitions.
AB  - The current research and development of 2D (matrix-shaped) transducer arrays to
      acquire 3D ultrasound data sets provides new insights into medical ultrasound
      applications and in particular into elastography. Until very recently, tissue
      strain estimation techniques commonly used in elastography were mainly 1D or 2D
      methods. In this paper, a 3D technique estimating biological soft tissue
      deformation under load from ultrasound radiofrequency volume acquisitions is
      introduced. This method locally computes axial strains, while considering lateral
      and elevational motions. Optimal deformation parameters are estimated as those
      maximizing a similarity criterion, defined as the normalized correlation
      coefficient, between an initial region and its deformed version, when the latter
      is compensated for according to these parameters. The performance of our
      algorithm was assessed with numerical data reproducing the configuration of
      breast cancer, as well as a physical phantom mimicking a pressure ulcer.
      Simulation results show that the estimated strain fields are very close to the
      theoretical values, perfectly discriminating between the harder lesion and the
      surrounding medium. Experimental strain images of the physical phantom
      demonstrated the different structures of the medium, even though they are not all
      detectable on the ultrasound scans. Finally, both simulated and experimental
      results demonstrate the ability of our algorithm to provide good-quality
      elastograms, even in the conditions of significant out-of-plane motion.

PMID- 18823815
TI  - Comparison of the performance of the LIAISON VZV-IgG and VIDAS automated enzyme
      linked fluorescent immunoassays with reference to a VZV-IgG time-resolved
      fluorescence immunoassay and implications of choice of cut-off for LIAISON assay.
AB  - BACKGROUND: Determination of Varicella Zoster virus (VZV) immune status in
      pregnant women without history of chickenpox is important in identifying those
      who genuinely need VZV immune globulin prophylaxis following significant exposure
      to chickenpox or shingles. Immune status testing requires highly sensitive and
      specific immunoassays for timely and accurate results. OBJECTIVES: To compare the
      performance of DiaSorin LIAISON and Biomerieux VIDAS VZV-IgG assays with
      reference to a VZV-IgG time-resolved fluorescence immunoassay (TRFIA). STUDY
      DESIGN: A panel of sera collected from 65 pregnant contacts of VZV and 62
      individuals tested for VZV immunity was tested in all three assays. Dose-response
      curves were generated using International Standards W1044 and 90/690. RESULTS:
      Sensitivity and specificity of VIDAS compared to VZV-TRFIA was 54.5% and 97.9%
      respectively and for LIAISON compared to VZV-TRFIA was 67% and 100% respectively.
      Both assays correlated well with TRFIA with R2 correlation coefficients of 0.79
      and 0.76 respectively. Dose-response curves showed both Standards behaved in a
      similar manner in each assay. For VIDAS, the test cut-off value of 0.9 correlated
      with 275-280mIU/ml and for LIAISON a cut-off value of 150mIU/ml correlated with
      208-219mIU/ml. CONCLUSIONS: By dose-response data and in comparison with TRFIA,
      LIAISON is more sensitive and specific than VIDAS.

PMID- 18823816
TI  - Clinical and epidemiological aspects of human bocavirus infection.
AB  - Human bocavirus was recently described as a novel member of the Parvoviridae to
      infect humans. Based on accumulating clinical and epidemiological data the virus
      is currently being associated with respiratory infections in young children and
      infants and is furthermore discussed as causative agent of gastrointestinal
      illness.

PMID- 18823817
TI  - Development of working reference materials for clinical virology.
AB  - Nucleic acid amplification technique (NAT)-based assays are replacing traditional
      diagnostic methods in clinical laboratories. However, many of these assays are
      developed in-house and the lack of standardised reference materials has hindered
      assay implementation and control. Consequently, in the UK, the Clinical Virology
      Network (CVN), the National Institute for Biological Standards and Control
      (NIBSC), and the Health Protection Agency (HPA), are working in collaboration to
      develop working standards or 'run controls' for diagnostic NAT-based assays,
      particularly real-time PCR. These run controls are intended for use in
      microbiology laboratories and are designed to be extracted and amplified in the
      same way as clinical samples and included in each assay run. The aim is to enable
      clinical laboratories to continuously monitor the performance of their diagnostic
      NAT assays on a run-by-run basis allowing inter-laboratory comparisons, and
      ultimately improving the consistency of results. At present, eight candidate run
      controls representing clinically relevant viral targets have been prepared for
      evaluation by CVN laboratories. Data have been returned on the performance of
      each run control in routine diagnostic assays. Preliminary results presented here
      indicate a high level of variability in intra- and inter-assay detection of these
      targets, highlighting the need for standardisation of assays within molecular
      diagnostics.

PMID- 18823818
TI  - Prevalence of human gammaretrovirus XMRV in sporadic prostate cancer.
AB  - BACKGROUND: We previously identified a novel exogenous gammaretrovirus
      (xenotropic murine leukemia virus-related gammaretrovirus (XMRV)) using a pan
      viral microarray. XMRV is the first MLV-related virus found in human infection.
      Forty percent (8/20) of familial prostate cancer patients homozygous for a
      mutation in RNase L (R462Q) were positive for XMRV, while the virus was rarely
      (1/66) detected in familial prostate cancer patients heterozygous for R462Q or
      carrying the wild type allele. OBJECTIVES: To determine the presence of XMRV in
      non-familial prostate cancer samples. STUDY DESIGN: RNA from prostate tissue was
      analyzed for XMRV using nested RT-PCR. In all samples, RNase L (R462Q) genotyping
      was performed using an allele-specific PCR. RESULTS: XMRV-specific sequences were
      detected in one of 105 tissue samples from non-familial prostate cancer patients
      and from one of 70 tissue samples from men without prostate cancer. The two XMRV
      positive patients were wild type or heterozygous for the R462Q mutation and thus
      carried at least one fully functional RNase L allele. CONCLUSIONS: XMRV was
      rarely detected in non-familial prostate cancer samples from Northern European
      patients. The homozygous mutation R462Q (QQ) was significantly underrepresented
      (<6%) in this cohort when compared to other studies (11-17%).

PMID- 18823819
TI  - Validation of an algorithm for the diagnosis of Restless Legs Syndrome: The
      Restless Legs Syndrome-Diagnostic Index (RLS-DI).
AB  - BACKGROUND: There is a need for structured methods to improve sensitivity and
      specificity of diagnostic decision making in Restless Legs Syndrome (RLS). We
      present the RLS-Diagnostic Index (RLS-DI), a diagnostic algorithm which combines
      essential and supportive diagnostic criteria from patient interviews,
      polysomnography and neurological examination in an adaptive procedure. METHOD:
      The RLS-DI consists of 10 items which are related to the essential diagnostic
      criteria established by the International RLS Study Group (five items) as well as
      their supportive criteria (3 items) and features associated with RLS (2 items).
      Items have to be completed using three categories per item that address frequency
      of occurrence of symptoms or certainty of presence or absence of other diagnostic
      information. Negative weights were given when the clinically most relevant items
      were not present. The RLS-DI was administered in a telephone interview to 179
      patients (86 with RLS, 93 with other sleep disorders) of the 21 month cohort of
      one sleep center in Germany. RESULTS: With receiver-operating characteristics, a
      cut-off of >or= 11 points on a scale ranging from -22 (no RLS) to 20 (definite
      RLS) was identified by comparing the RLS-DI total score to the diagnosis of two
      independent sleep experts. Sensitivity was 93.0%, specificity was 98.9%, and
      96.1% of the patients could be correctly diagnosed. Specificity was higher in
      items related to supportive or associated diagnostic information (95.7%) than in
      those related to the essential diagnostic criteria (81.7%). Patients with RLS
      scored a higher RLS-DI than those with primary insomnia or other neurological or
      psychiatric disorders (p < .001). CONCLUSION: The RLS-DI demonstrated the ability
      to validly diagnose an actual and persistently present Restless Legs Syndrome in
      patients of a sleep lab population and to exclude those patients whose sleep
      disturbances have other causes.

PMID- 18823820
TI  - Impaired phenotype and function of monocyte derived dendritic cells in pulmonary
      tuberculosis.
AB  - Pulmonary tuberculosis (PTB) is often associated with impaired immunological
      functions. Blood monocytes, which can differentiate into dendritic cells upon
      cytokine stimulation, play a central role in adequate immune reactivity. Here, we
      investigated the morphologic, phenotypic and functional characteristics of in
      vitro-generated monocyte derived dendritic cells (MoDC) from PTB patients in
      comparison with healthy subjects. Phenotypic analysis revealed a defective
      differentiation of MoDC in PTB patients as assessed by a strong down regulation
      of CD1a, MHC II, CD80 and CD83 expression and impaired allostimulatory function
      under the influence of IL-4 and GM-CSF. In contrast, the expression of CD86 was
      not affected and remained same as in healthy subjects. Furthermore, the
      maturation status of lipopolysaccharide (LPS) stimulated MoDC was not optimal in
      PTB. However, the MoDC of PTB patients produced significantly higher levels of
      TNF-alpha and IL-6 but lower levels of IL-12 compared to healthy subjects. These
      findings suggest that there is a fundamental defect in the differentiation and
      maturation of dendritic cells during PTB that may compromise the antigen
      presentation and subsequent immune functions.

PMID- 18823821
TI  - Intrahepatic regulatory T cells are phenotypically distinct from their peripheral
      counterparts in chronic HBV patients.
AB  - Peripheral blood CD4+CD25+ regulatory T cells (Treg) prevent the development of
      strong HBV-specific T cell responses in vitro. In this study, we examined the
      phenotype of FoxP3+ regulatory T cells in the liver of patients with a chronic
      HBV infection. We showed that the liver contained a population of CD4+FoxP3+
      cells that did not express CD25, while these cells were absent from peripheral
      blood. Interestingly, intrahepatic CD25-FoxP3+CD4+ T cells demonstrated lower
      expression of HLA-DR and CTLA-4 as compared to their CD25+ counterparts. Patients
      with a high viral load have a higher proportion of regulatory T cells in the
      liver, but not in blood, compared to patients with a low viral load. In
      conclusion, the intrahepatic Treg are phenotypically distinct from peripheral
      blood Treg. Our data suggest that the higher proportion of intrahepatic Treg
      observed in patients with a high viral load may explain the lack of control of
      viral replication.

PMID- 18823822
TI  - NK and NKT cells in liver injury and fibrosis.
AB  - The innate immune mechanisms of the liver represent an important first line of
      defense against bacterial products, toxins, and food antigens coming from the
      intestine. Natural Killer (NK) and Natural Killer T cells (NKT) are components of
      the innate immune system with increased presence in the liver compared to other
      organs and have been reported to participate in the inflammatory processes during
      hepatic diseases. However significant confusion has been noted in this field
      mainly due to changes in the characterization of these cells as new knowledge
      accumulates and due to differences in the approaches used for their study. Both
      cell types can mediate hepatic injury in several models but studies in human
      liver diseases have not managed to fully explain their functions. However
      accumulating evidence supports an antifibrotic role of NK cells mainly via an
      inhibitory effect on hepatic stellate cells by inducing apoptosis and via
      production of interferon-gamma. Therefore, downregulation of NK cells during most
      types of liver injury may facilitate liver fibrosis. Data about the role of NKT
      cells in liver fibrosis are limited. This review will summarize the studies about
      the role of NK and NKT cells in liver diseases with a special interest in hepatic
      injury and liver fibrosis.

PMID- 18823823
TI  - Sudden infant death syndrome: do ion channels play a role?

PMID- 18823824
TI  - Diclofenac-loaded biopolymeric nanosuspensions for ophthalmic application.
AB  - Polymeric nanoparticle suspensions (NS) were prepared from poly(lactide-co
      glycolide) and poly(lactide-co-glycolide-leucine) {poly[Lac(Glc-Leu)]}
      biodegradable polymers and loaded with diclofenac sodium (DS), with the aim of
      improving the ocular availability of the drug. NS were prepared by emulsion and
      solvent evaporation technique and characterized on the basis of physicochemical
      properties, stability, and drug release features. The nanoparticle system showed
      an interesting size distribution suitable for ophthalmic application. Stability
      tests (as long as 6 months' storage at 5 degrees C or at 25 degrees C/60%
      relative humidity) or freeze-drying were carried out to optimize a suitable
      pharmaceutical preparation. In vitro release tests showed a extended-release
      profile of DS from the nanoparticles. To verify the absence of irritation toward
      the ocular structures, blank NS were applied to rabbit eye and a modified Draize
      test performed. Polymer nanoparticles seemed to be devoid of any irritant effect
      on cornea, iris, and conjunctiva for as long as 24 hours after application, thus
      apparently a suitable inert carrier for ophthalmic drug delivery.

PMID- 18823825
TI  - Quantification of sunitinib in human plasma by high-performance liquid
      chromatography-tandem mass spectrometry.
AB  - A rapid, sensitive and specific method was developed and validated using LC/MS/MS
      for determination of sunitinib in human plasma. Sample preparation involved a
      liquid-liquid extraction by the addition of 0.2mL of plasma with 4.0mL tert-butyl
      methyl-ether extraction solution containing 25ng/mL of the internal standard
      clozapine. Separation of compounds was achieved on a C18 (50mmx2.1mm i.d.,
      3.5microm) analytical column using a mobile phase consisting of acetonitrile/H20
      (65:35, v/v) containing 0.1% formic acid and isocratic flow at 0.150mL/min for
      3min. The analytes were monitored by tandem-mass spectrometry with electrospray
      positive ionization. Linear calibration curves in human plasma were generated
      over the range of 0.2-500ng/mL with values for the coefficient of determination
      of >0.9950. Within- and between day precision and accuracy were < or =10%. The
      method was applied to the quantitation of sunitinib in plasma samples from a
      patient receiving daily oral therapy with sunitinib.

PMID- 18823826
TI  - Enantiomeric separation of bupropion enantiomers by electrokinetic
      chromatography: quantitative analysis in pharmaceutical formulations.
AB  - The first CE method enabling the quantitation of the two enantiomers of bupropion
      was developed in this work. Electrokinetic chromatography (EKC) mode using
      cyclodextrins as chiral selectors was employed. A study on the enantiomeric
      separation ability of different neutral and anionic CDs was carried out. Sulfated
      beta-CD was shown to provide the highest values for the enantiomeric resolution.
      The influence of some experimental conditions, such as pH, chiral selector
      concentration, temperature, and separation voltage on the enantiomeric separation
      of bupropion was also studied. The use of 10 mM sulfated-beta-CD in 50 mM borate
      buffer (pH 9.0) with an applied voltage of 30 kV and a temperature of 30 degrees
      C enabled the separation of the enantiomers of bupropion with high resolution (Rs
      > 7) and short analysis time (approximately 3.5 min). Finally, the method was
      successfully applied to the quantitation of bupropion in two pharmaceutical
      formulations.

PMID- 18823827
TI  - Structural variants of biodegradable polyesterurethane in vivo evoke a cellular
      and angiogenic response that is dictated by architecture.
AB  - The aim of this study was to investigate an in vivo tissue response to a
      biodegradable polyesterurethane, specifically the cellular and angiogenic
      response evoked by varying implant architectures in a subcutaneous rabbit implant
      model. A synthetic biodegradable polyesterurethane was synthesized and processed
      into three different configurations: a non-porous film, a porous mesh and a
      porous membrane. Glutaraldehyde cross-linked bovine pericardium was used as a
      control. Sterile polyesterurethane and control samples were implanted
      subcutaneously in six rabbits (n=12). The rabbits were killed at 21 and 63 days
      and the implant sites were sectioned and histologically stained using
      haemotoxylin and eosin (H&E), Masson's trichrome, picosirius red and immunostain
      CD31. The tissue-implant interface thickness was measured from the H&E slides.
      Stereological techniques were used to quantify the tissue reaction at each time
      point that included volume fraction of inflammatory cells, fibroblasts,
      fibrocytes, collagen and the degree of vascularization. Stereological analysis
      inferred that porous scaffolds with regular topography are better tolerated in
      vivo compared to non-porous scaffolds, while increasing scaffold porosity
      promotes angiogenesis and cellular infiltration. The results suggest that this
      biodegradable polyesterurethane is better tolerated in vivo than the control and
      that structural variants of biodegradable polyesterurethane in vivo evoke a
      cellular and angiogenic response that is dictated by architecture.

PMID- 18823828
TI  - Capture of bacteria by flexible carbon nanotubes.
AB  - Capture of bacteria with flexible carbon nanotubes (CNTs) was done in vitro.
      Bundles of single-walled carbon nanotubes (SWCNTs) or multi-walled carbon
      nanotubes (MWCNTs) was mixed with Streptococcus mutans. Precipitation assays and
      colony-forming unit formation assays showed free S. mutans in the solution was
      significantly decreased by the addition of the CNTs. Observation of the
      precipitate by scanning electron microscopy showed bacterial adhesion to CNTs. It
      has been shown that CNTs of different diameters have significantly different
      effects on the precipitation efficiency, and the manners in which they capture
      the cells are different. We found that MWCNTs (diameter of approximately 30 nm)
      had the highest precipitation efficiency, which was attributable to both their
      adequate dispersibility and aggregation activity. From observations by scanning
      electron microscopy, bundles of SWCNTs and thin MWCNTs (diameter of approximately
      30 nm), which were moderately flexible, were easily wound around the curved
      surface of S. mutans. Bare CNTs having high adhesive ability could be useful as
      biomaterials, e.g., as tools for the elimination of oral pathogens at the nano
      level.

PMID- 18823829
TI  - Iatrogenic biliary injuries during laparoscopic cholecystectomy. A continuing
      threat.
AB  - BACKGROUND: Despite improvement in the technique and increasing experience,
      complications of different nature and severity continue to occur during
      laparoscopic cholecystectomy all around the world. We present bile duct injuries
      in this series with regards to the incidence, severity and management of this
      problem. STUDY DESIGN: Descriptive. PLACE AND DURATION: Department of surgery,
      Liaquat University of medical and Health Sciences, Jamshoro and other private
      hospitals at Hyderabad city during April 2003 to December 2007. MATERIALS AND
      METHODS: A total of 1132 patients with symptomatic gallstone disease were
      included in the study regardless of their age and gender. Laparoscopic
      cholecystectomy by classical four-port technique performed in all cases with few
      amendments as per situation. Patients with growth in gallbladder and with severe
      associated medical or cardiac problems were excluded from the study. Details of
      every patient collected on a proforma and data finally analyzed on SPSS version
      10. RESULTS: Of total 1132 patients, 1088 (96%) were females and 44 (4%) were
      males with a mean age of 47.64 years. Elective laparoscopic cholecystectomy was
      performed in 1118 (98.7%) patients whereas emergency laparoscopic cholecystectomy
      was done in 14 (1.23%) patients. Various types of common bile duct injuries as
      well as post -operative bile leaks and their management is discussed with a view
      to improve upon the technique and out come. CONCLUSION: Iatrogenic biliary
      injuries continue to occur despite tremendous overall improvement in technique
      and expertise.

PMID- 18823830
TI  - The 'Gallipot' splash guard: a simple and effective safety measure for wound
      irrigation.

PMID- 18823831
TI  - Avoiding the operated on look in multiple face lifts.
AB  - AIM: Reviewing 43 patients of ours who have had three or more face lifts, we
      wanted to demonstrate that it is possible to avoid the multi-operated on look.
      MATERIAL AND METHODS: Forty-three patients have been operated on three times or
      more: 42 females and one male. Thirty-six patients had three face lifts, six had
      four face lifts, one patient had five face lifts. The mean age at time of surgery
      was 50.3 years for the first face lift, 56.7 for the second, and 64.2 for the
      third face lift. These patients were operated on by the same surgeon using a
      technique which has evolved over the years but with the same basic goal of hiding
      the scars and of minimising hairline displacement. General appearance, scars and
      hairline displacement were evaluated in patients who had had three or more face
      lifts. RESULTS: The results of the evaluation of our 43 multi-operated on face
      lift patients were as follows: 35 patients did not appear to have had face lifts,
      eight patients did appear to have had face lifts, but with satisfactory
      appearance, 30 patients had no visible scars at a conversational distance, 10
      patients had slightly visible scars when their hair was lifted, five had obvious
      scars when the hair was lifted, 34 patients had a normal hairline, six patients
      had a slightly receding hairline at the temporal level and three had hair loss at
      the level of the temporal scar. CONCLUSIONS: New technical improvements allow the
      preservation of a natural appearance, with well-hidden scars and a well-placed
      hairline. The common opinion that several repeated face lifts should be avoided
      because they give an unnatural appearance and severe sequelae in terms of scars
      and hairline displacement has not been confirmed by our clinical experience with
      43 patients having undergone at least three face lifts.

PMID- 18823832
TI  - Sickle cell disease, a benign cause of numb chin syndrome.

PMID- 18823834
TI  - Chronic rhinosinusitis and fatigue: a common but underappreciated association.

PMID- 18823836
TI  - Acute effects of newer antipsychotic drugs on glucose metabolism.

PMID- 18823838
TI  - Alternative solutions to geriatric workforce deficit.

PMID- 18823840
TI  - Allopurinol hypersensitivity and DRESS syndrome.

PMID- 18823842
TI  - Filariasis caused by Loa loa is also a cause of angioedema.

PMID- 18823843
TI  - Reduced high-density lipoprotein cholesterol in patients receiving rosiglitazone
      and fenofibrate.

PMID- 18823844
TI  - Extreme polyuria: at the heart of the answer.

PMID- 18823845
TI  - Hepatocellular carcinoma: a pledge for evidence-based medicine.

PMID- 18823846
TI  - Hepatocellular carcinoma: failure to diagnose does not equal malpractice.

PMID- 18823847
TI  - Coming clean: waterless hand cleaners--which to choose?

PMID- 18823848
TI  - There is no substitute for brilliance except for experience.

PMID- 18823849
TI  - Broken brains.

PMID- 18823850
TI  - Extensively drug-resistant tuberculosis.
AB  - Extensively drug-resistant tuberculosis (XDR-TB) is defined as Mycobacterium
      tuberculosis infection that is resistant to isoniazid, rifampin, any
      fluoroquinolone, and any injectable drug (amynoglicosides or polypetides).
      Although initially described in South Africa, it has emerged as a global threat,
      and cases have been reported from several countries, including the United States.
      XDR-TB has emerged mainly as a consequence of previous inadequate or poorly
      administered treatment, from failure of the public health infrastructure. As the
      diagnosis of this condition requires antibiotic susceptibility confirmation, a
      broad network of reference laboratories and the development of faster and more
      accurate tests for the identification of active cases of tuberculosis are
      urgently required. The treatment of XDR-TB is challenging and requires the use of
      multiple second-line drugs and, potentially, surgery. Infection control measures
      do not differ from those used for susceptible cases but may require more
      stringent application.

PMID- 18823851
TI  - Declining length of hospital stay for pneumonia and postdischarge outcomes.
AB  - OBJECTIVE: This study was designed to assess 8-year trends in the duration of
      hospitalization for community-acquired pneumonia and to evaluate the impact of
      declining length of stay on postdischarge short-term readmission and mortality.
      METHODS: We conducted a prospective observational cohort study of 1886 patients
      with community-acquired pneumonia who were discharged from a single hospital
      between March 1, 2000, and June 30, 2007. The main outcomes measured were all
      cause mortality and hospital readmission during the 30-day period after
      discharge. Regression models were used to identify risk factors associated with
      hospital length of stay and the adjusted associations between length of stay and
      mortality and readmission. RESULTS: Factors associated with a longer hospital
      stay included the number of comorbid conditions, high risk classification on the
      Pneumonia Severity Index, bilateral or multilobe radiographic involvement, and
      treatment failure. Patients treated with an appropriate antibiotic were less
      likely to have an increased length of stay. The mean length of stay was
      significantly shorter during the 2006 to 2007 period (3.6 days) than during the
      2000 to 2001 period (5.6 days, P<.001). Despite the reduction in length of stay,
      there were no significant differences in the likelihood of death or readmission
      at 30 days between the 2 time periods. Adjusted multivariate analysis showed that
      patients with hospital stays less than 3 days did not have significant increases
      in postdischarge outcomes. CONCLUSION: The marked decreased in the length of stay
      for patients hospitalized with community-acquired pneumonia since 2000 has not
      been accompanied by an increase in short-term mortality or hospital readmission.

PMID- 18823852
TI  - Improving heart failure care with a reminder attached to the echocardiography
      report.

PMID- 18823853
TI  - Not so innocuous.

PMID- 18823854
TI  - A suspicious stroke.

PMID- 18823855
TI  - Rare red rash.

PMID- 18823856
TI  - Veiled villain.

PMID- 18823857
TI  - Synchronicity.

PMID- 18823858
TI  - Left ventricular hypertrophy and cardiovascular mortality by race and ethnicity.
AB  - BACKGROUND: Left ventricular hypertrophy is a major independent risk factor for
      cardiovascular mortality. The contribution of left ventricular hypertrophy to
      racial and ethnic differences in cardiovascular mortality is poorly understood.
      METHODS: We used data from the Third National Health and Nutrition Examination
      Survey and from the National Death Index to compare mortality for those with an
      electrocardiographic (ECG) diagnosis of left ventricular hypertrophy to those
      without left ventricular hypertrophy separately for whites, African Americans,
      and Latinos. We used Cox proportional hazards regression to control for other
      known prognostic factors. RESULTS: ECG left ventricular hypertrophy was
      significantly associated with 10-year cardiovascular mortality in all 3
      racial/ethnic groups, both unadjusted and adjusted for other known prognostic
      factors. The hazard ratio for this association was significantly greater for
      African Americans (2.31; 95% confidence interval [CI], 1.55-3.42) than for whites
      and Latinos (1.32; 95% CI, 1.14-1.76 and 2.11; 95% CI, 1.35-3.30, respectively),
      independent of systolic blood pressure. CONCLUSIONS: ECG left ventricular
      hypertrophy contributes more to the risk of cardiovascular mortality in African
      Americans than it does in whites. Using regression of ECG left ventricular
      hypertrophy as a goal of therapy might be a means to reduce racial differences in
      cardiovascular mortality; prospective validation is required.

PMID- 18823859
TI  - Emergence of fluoroquinolone resistance in outpatient urinary Escherichia coli
      isolates.
AB  - BACKGROUND: Because of high rates of trimethoprim-sulfamethoxazole resistance in
      Escherichia coli, Denver Health switched to levofloxacin as the initial therapy
      for urinary tract infections (UTIs) in 1999. We evaluated the effects of that
      switch 6 years later. METHODS: Levofloxacin prescriptions per 1000 outpatient
      visits and levofloxacin resistance in outpatient E. coli were evaluated over
      time. E. coli isolated in 2005 were further characterized by specimen source and
      antimicrobial susceptibilities. Risk factors for levofloxacin-resistant E. coli
      UTI among nonpregnant adult outpatients were evaluated in a case-control study.
      RESULTS: Between 1998 and 2005, levofloxacin use increased from 3.1 to 12.7
      prescriptions per 1000 visits (P<.01) and resistance in outpatients increased
      from 1% to 9% (P<.01). Although prescriptions for sulfonamide antibiotics
      decreased by half during the same period, E. coli resistance to trimethoprim
      sulfamethoxazole increased from 26.1% to 29.6%. Levofloxacin-resistant E. coli
      were more likely resistant to other antibiotics than levofloxacin-susceptible
      isolates (90% vs 43%, P<.0001). Risk factors for levofloxacin-resistant E. coli
      UTI were hospitalization (odds ratio for each week of hospitalization, 2.0; 95%
      confidence interval, 1.0-3.9) and use of levofloxacin (odds ratio, 5.6; 95%
      confidence interval, 2.1-27.5) within the previous year. CONCLUSION:
      Fluoroquinolone prescriptions increased markedly after an institutional policy
      change for empiric treatment of UTI, and a rapid increase in fluoroquinolone
      resistance among outpatient E. coli followed. Risk factors for infection with
      resistant E. coli were recent hospitalization and levofloxacin use. Risk factors
      should be considered before initiating empiric treatment with a fluoroquinolone.

PMID- 18823860
TI  - Gastric banding or bypass? A systematic review comparing the two most popular
      bariatric procedures.
AB  - OBJECTIVE: Bariatric surgical procedures have increased exponentially in the
      United States. Laparoscopic adjustable gastric banding is now promoted as a
      safer, potentially reversible and effective alternative to Roux-en-Y gastric
      bypass, the current standard of care. This study evaluated the balance of patient
      oriented clinical outcomes for laparoscopic adjustable gastric banding and Roux
      en-Y gastric bypass. METHODS: The MEDLINE database (1966 to January 2007),
      Cochrane clinical trials database, Cochrane reviews database, and Database of
      Abstracts of Reviews of Effects were searched using the key terms gastroplasty,
      gastric bypass, laparoscopy, Swedish band, and gastric banding. Studies with at
      least 1 year of follow-up that directly compared laparoscopic adjustable gastric
      banding with Roux-en-Y gastric bypass were included. Resolution of obesity
      related comorbidities, percentage of excess body weight loss, quality of life,
      perioperative complications, and long-term adverse events were the abstracted
      outcomes. RESULTS: The search identified 14 comparative studies (1 randomized
      trial). Few studies reported outcomes beyond 1 year. Excess body weight loss at 1
      year was consistently greater for Roux-en-Y gastric bypass than laparoscopic
      adjustable gastric banding (median difference, 26%; range, 19%-34%; P < .001).
      Resolution of comorbidities was greater after Roux-en-Y gastric bypass. In the
      highest-quality study, excess body weight loss was 76% with Roux-en-Y gastric
      bypass versus 48% with laparoscopic adjustable gastric banding, and diabetes
      resolved in 78% versus 50% of cases, respectively. Both operating room time and
      length of hospitalization were shorter for those undergoing laparoscopic
      adjustable gastric banding. Adverse events were inconsistently reported.
      Operative mortality was less than 0.5% for both procedures. Perioperative
      complications were more common with Roux-en-Y gastric bypass (9% vs 5%), whereas
      long-term reoperation rates were lower after Roux-en-Y gastric bypass (16% vs
      24%). Patient satisfaction favored Roux-en-Y gastric bypass (P=.006). CONCLUSION:
      Weight loss outcomes strongly favored Roux-en-Y gastric bypass over laparoscopic
      adjustable gastric banding. Patients treated with laparoscopic adjustable gastric
      banding had lower short-term morbidity than those treated with Roux-en-Y gastric
      bypass, but reoperation rates were higher among patients who received
      laparoscopic adjustable gastric banding. Gastric bypass should remain the primary
      bariatric procedure used to treat obesity in the United States.

PMID- 18823861
TI  - Exercise blood pressure response, albuminuria, and arterial stiffness in
      hypertension.
AB  - BACKGROUND: A hypertensive response to exercise is associated with high
      cardiovascular risk, whereas the data about its relation to surrogates of
      subclinical atherosclerosis are scarce. We investigated the relationships of a
      hypertensive response to exercise with urinary albumin excretion and arterial
      stiffness in hypertensives. METHODS: There were 171 untreated males (mean age 52
      years, all Caucasian) with stage I-II essential hypertension and a negative
      treadmill exercise test divided into those with a hypertensive response to
      exercise (n=48) (peak exercise systolic blood pressure > or =210 mm Hg) and to
      those with normal blood pressure response (n=123). Albumin-to-creatinine ratio
      values were determined as the mean of 3 nonconsecutive morning spot urine
      samples, and arterial stiffness was evaluated on the basis of carotid-to-femoral
      pulse wave velocity. RESULTS: Patients with a hypertensive response to exercise
      compared with those with normal blood pressure response exhibited greater log
      albumin-to-creatinine ratio (1.52+/-0.59 vs 0.97+/-0.33 mg/g) and higher pulse
      wave velocity (8.7+/-1.6 vs 7.7+/-1.2 m/s), independent of potentially
      confounding demographic and clinical factors. Resting systolic blood pressure
      (odds ratio [OR] 1.11, 95% confidence interval [CI], 1.06-1.16), body mass index
      (OR 1.12, 95% CI, 1.02-1.23), resting heart rate (OR 0.96, 95% CI, 0.93-0.99),
      and albumin-to-creatinine ratio (OR 7.45, 95% CI, 2.54-21.83) were independently
      associated with a hypertensive response to exercise. CONCLUSION: A hypertensive
      response to exercise is related to augmented albumin-to-creatinine ratio and
      arterial stiffness, reflecting accelerated subclinical atherosclerosis. The
      association of albumin excretion with exercise blood pressure response suggests
      that albuminuria constitutes an important factor in the interpretation of the
      hypertensive response to exercise-associated risk.

PMID- 18823862
TI  - Primary syphilis: serological treatment response to doxycycline/tetracycline
      versus benzathine penicillin.
AB  - BACKGROUND: Benzathine penicillin G is the treatment of choice for infectious
      syphilis, but tetracycline and doxycycline are believed to be effective second
      line treatments. The objective of this study was to assess the serological
      response from treatment of primary syphilis with benzathine penicillin compared
      with doxycycline or tetracycline. METHODS: We examined rapid plasma reagin
      serological test results of all first-time primary syphilis patients in Alberta,
      Canada from 1980 to 2001 and compared treatment with single dose of penicillin
      with 14-day course of oral doxycycline (100 mg twice a day) or oral tetracycline
      (500 mg 4 times a day). Serological treatment success was defined as a minimum 4
      fold decrease in baseline rapid plasma reagin test antibody titer within 6
      months, or > or =8-fold decrease within 12 months, or > or =16-fold decrease by
      24 months. The median time to successful response was estimated, and factors
      associated with treatment success were identified by unadjusted logistic
      regression. RESULTS: Of the 445 primary syphilis cases with available treatment
      outcome data, 420 (94.4%) received penicillin and 25 (5.6%) received
      doxycycline/tetracycline. The serological treatment success rate was 97.4% in the
      penicillin group (409/420) and 100% in the doxycycline/tetracycline group
      (25/25), and not significantly different. The estimated median time to
      serological treatment success was 72.0 days (mean=101.7, range 10-603) in
      penicillin and 43.0 days (mean=78.6, range 15-334) in doxycycline/tetracycline
      treated patients; however, this difference was not statistically significant
      (P=0.16). CONCLUSION: Doxycycline/tetracycline had a similarly high serological
      treatment success rate when compared with penicillin in the treatment of primary
      syphilis.

PMID- 18823863
TI  - Incidence and significance of a positive troponin test in bacteremic patients
      without acute coronary syndrome.
AB  - BACKGROUND: Since the introduction of troponin for the diagnosis of myocardial
      infarction, several studies have shown additional conditions in which troponin is
      elevated, including sepsis. The objective of this study was to determine the
      incidence of an elevated troponin in patients with bacteremia and its
      significance. METHODS: This was a prospective, noninterventional study. Patients
      with a positive blood culture were included. Cardiac troponin I (cTnI) was
      determined within 4 days of blood culture. A repeat electrocardiogram was
      obtained in a sample of patients with elevated cTnI and in patients with a
      negative troponin test. Demographic, clinical, and microbiological data were
      obtained for all patients. RESULTS: A total of 159 bacteremic patients were
      included. Positive cTnI was detected in 69 patients (43%). Elevated cTnI was
      associated with a number of underlying diseases, hospitalization ward, severity
      of the systemic inflammatory condition, and kidney function (P<.05-.001). A
      repeat electrocardiogram was performed in 39 patients with a positive cTnI and in
      28 patients with a negative cTnI. Two of 39 patients (5%) in the positive cTnI
      group had ischemic changes and 2 patients (5%) had nonspecific changes, whereas
      only 1 patient (4%) with a negative cTnI had nonspecific changes. Bivariate
      analysis revealed a statistically significant association for positive cTnI and
      mortality; however, on multivariate analysis this was no longer significant.
      CONCLUSION: Forty-three percent of bacteremic patients had an elevated cTnI. Risk
      factors for elevated cTnI were severity of the underlying infection, renal
      function, and underlying cardiac disease. Increased cTnI was found to be a
      dependent risk factor and a surrogate marker for death.

PMID- 18823864
TI  - Surgical and obstetric outcomes in adults with sickle cell disease.
AB  - BACKGROUND: Sickle cell disease patients are more likely than the general
      population to undergo surgery and usually do so at a younger age. Female sickle
      cell disease patients also have special gynecological and obstetric issues
      related to their disease. METHODS: We collected data through standardized
      clinical report forms, patient interviews, and medical records from 509 adult
      sickle cell disease patients. Logistic regression was used to estimate the
      association between multiple variables and each of the surgery types. We also
      determined the prevalence and outcomes of pregnancy in 284 women with sickle cell
      disease in this population. RESULTS: Almost 50% of patients aged 18-27 years had
      had a cholecystectomy. Mean corpuscular hemoglobin, total bilirubin, and lactate
      dehydrogenase were significantly higher in the postcholecystectomy group; 9.5% of
      504 individuals had undergone splenectomy. Hematocrit, body mass index, and red
      blood cell count were significantly higher in the postsplenectomy group. Hip
      replacement had been performed in 9.2% of individuals, with the prevalence
      increasing as early as the fourth decade and continuing to increase through the
      sixth decade of life. A history of pregnancy was present in 190 women (67%). Of
      410 pregnancies, only 53.9% resulted in live births, 16.6% were voluntarily
      terminated, and 29.5% were complicated by miscarriage, still birth, or ectopic
      implantation. CONCLUSIONS: Sickle cell disease continues to have a strong effect
      on the mean age for common surgeries and impacts pregnancy outcomes. We conclude
      that this population has a unique surgical and obstetric history that should be
      further studied to provide insight into potentially more effective preventive
      approaches to end-organ damage.

PMID- 18823865
TI  - A model for quality improvement programs in academic departments of medicine.

PMID- 18823866
TI  - Magnetic resonance imaging features of the discrete epiphyseal radiolucency: a
      problem-solving approach to differential diagnosis.
AB  - Discrete radiolucencies in the epiphysis of the long bones may be a major
      radiographic finding in many arthropathies and synovial-based processes, and also
      in various osteolytic tumors and tumor-like lesions. In addition, a number of
      miscellaneous bone disorders, particularly infection and avascular necrosis, may
      present as discrete epiphyseal radiolucencies. Magnetic resonance imaging is
      frequently used in the diagnostic workup of these lesions. Our purpose was to
      review and illustrate, in a problem-solving approach, the potential contributions
      of magnetic resonance imaging in the characterization of discrete epiphyseal
      radiolucent lesions.

PMID- 18823867
TI  - Computed tomography and magnetic resonance imaging features of lesions of the
      renal medulla and sinus.
AB  - The kidneys can harbor a wide variety of lesions, many of which can be visualized
      by computed tomography and magnetic resonance imaging. In this article, the
      pertinent renal anatomic relationships as well as the histologic composition and
      function of the renal medulla and sinus are reviewed. Additionally, computed
      tomography and magnetic resonance imaging features of renal sinus and medullary
      lesions in adult patients are presented. This article reviews the salient imaging
      features of various malignant, benign neoplastic, and nonneoplastic lesions of
      the sinus and medulla.

PMID- 18823868
TI  - Computed tomographic enterography and enteroclysis: pearls and pitfalls.
AB  - Computed tomographic (CT) enterography and enteroclysis improve visualization of
      the small bowel mucosa and wall in comparison with traditional CT and
      fluoroscopic studies by distending the small bowel through enteric hyperhydration
      with a negative contrast agent. Although CT enterography is performed with oral
      hyperhydration, CT enteroclysis requires the placement of an enteroclysis tube,
      often in patients who are unable to orally consume the amount of liquid. When
      tolerated, CT enterography is often preferred due to its lack of invasiveness.
      Magnetic resonance enterography and enteroclysis are other modalities that are
      still being studied and show promise in the imaging of small bowel. Unlike small
      bowel follow-through, conventional enteroclysis, or capsule endoscopy,
      extraenteric findings are best assessed on CT enterography. These include
      findings in the surrounding mesentery, perienteric fat, and the adjacent solid
      organs that may be associated with the small bowel process and include fistulas
      or abscesses, mural hyperenhancement, prominent vasa recta, and other
      inflammatory changes. CT enterography has developed into the first-line modality
      in the imaging of Crohn's disease and is considered the most appropriate imaging
      modality in patients with suspected Crohn's disease. It is also increasingly
      being used in the assessment of small bowel infections, neoplasms, adhesions, and
      polyps.

PMID- 18823869
TI  - [Oncoforum in urology and review of the literature].
AB  - OBJECTIVE: To summarize the major new findings in prostate cancer in radiation
      oncology in the last year. METHODS: A review of the 2007 annual meetings of the
      ASCO, ASTRO, EAU, AUA annual congresses and bibliographic review. RESULTS:
      Incidence of prostate carcinoma is increasing in France (62 000 cases in 2005),
      but its mortality rate is stable (9202 deaths). This finding justified the active
      surveillance option for selected patients. For the initial staging or in case of
      biochemical relapse after surgery, the 11-C-choline PET/CT has not today proven
      any meaningful clinical benefit. Dose escalation in exclusive external beam
      radiotherapy has now proven its potential interest in several randomized trials
      and also in some retrospective data: biochemical control is regularly increased
      in case of higher dose. Even if this dose escalation increased also toxicity,
      this is always acceptable. Some unconfirmed data suggested that this benefit in
      biochemical control is translated in a better clinical disease-free survival. The
      role of prophylactic nodal irradiation is still debated. On the other hand, in
      the unfavorable group, a long-term androgen deprivation (3 years at least) is
      more efficient than a short-term androgen deprivation in an EORTC randomized
      trial. In more advanced disease, discussion between imediate and deferred
      hormonal treatment is also a matter of debate; but it seems that patients with a
      PSA higher than 50 ng/ml or a PSA doubling time lower than 12 months must
      received immediate hormonal manipulation. However, late effects of the hormonal
      treatment are now recognized: metabolic syndrom is often diagnosed after androgen
      deprivation and seems to increase cardio-vascular mortality. All local treatments
      had deleterious effects on quality of life and the initial conditions of the
      patients must be incorporated in the treatment choice. CONCLUSION: Last year has
      seen many publications on prostate cancer, some of them could impact on our
      clinical practice.

PMID- 18823871
TI  - Interfacial shear rheology of protein-surfactant layers.
AB  - The shear rheology of adsorbed or spread layers at air/liquid and liquid/liquid
      phase boundaries is relevant in a wide range of technical applications such as
      mass transfer, monolayers, foaming, emulsification, oil recovery, or high speed
      coating. Interfacial shear rheological properties can provide important
      information about interactions and molecular structure in the interfacial layer.
      A variety of measuring techniques have been proposed in the literature to measure
      interfacial shear rheological properties and have been applied to pure protein or
      mixed protein adsorption layers at air/water or oil/water interfaces. Such
      systems play for example an important role as stabilizers in foams and emulsions.
      The aim of this contribution is to give a literature overview of interfacial
      shear rheological studies of pure protein and protein/surfactant mixtures at
      liquid interfaces measured with different techniques. Techniques which utilize
      the damping of waves, spectroscopic or AFM techniques and all micro-rheological
      techniques will not discuss here.

PMID- 18823872
TI  - Time-lapse cinematography of dynamic changes occurring during in vitro
      development of human embryos.
AB  - OBJECTIVE: The purpose of this study was to clarify developmental changes of
      early human embryos by using time-lapse cinematography (TLC). STUDY DESIGN: For
      human ova, fertilization and cleavage, development of the blastocyst, and
      hatching, as well as consequent changes were repeatedly photographed at intervals
      of 5-6 days by using an inverse microscope under stabilized temperature and pH.
      Photographs were taken at 30 frames per second and the movies were studied.
      RESULTS: Cinematography has increased our understanding of the morphologic
      mechanisms of fertilization, development, and behavior of early human embryos,
      and has identified the increased risk of monozygotic twin pregnancy based on
      prolonged incubation in vitro to the blastocyst stage. CONCLUSION: Using TLC, we
      observed the fertilization of an ovum by a single spermatozoon, followed by early
      cleavages, formation of the morula, blastocyst hatching, changes in the embryonic
      plates, and the development of monozygotic twins from the incubated blastocysts.

PMID- 18823873
TI  - Laparotomy operative note template constructed through a modified Delphi method.
AB  - OBJECTIVE: An operative note is indispensable to physician documentation and
      decision-making; however, there are no accepted standards for operative note
      content. Our aim was to use a modified Delphi consensus-building method to
      construct a uniform operative note template for laparotomy. STUDY DESIGN: Using
      Joint Commission on Accreditation of Healthcare Organizations requirements,
      literature review, and feedback from 15 medical malpractice defense attorneys, we
      compiled a draft operative note template of 31 elements. We surveyed 37
      Association of Professor of Gynecology and Obstetrics/Solvay scholars asking for
      their input on inclusion of each item as essential content of the operative note.
      RESULTS: Two iterations of the survey were required to reach a predetermined 75%
      level of consensus. Nine elements were eliminated from the template: 6 original
      and 3 expert-suggested elements. CONCLUSION: We provide an operative note
      template that was compiled through a Delphi process.

PMID- 18823874
TI  - "Preventive induction" fails to demonstrate benefits for mothers or newborn
      infants.

PMID- 18823875
TI  - Driving with a Congestion Assistant; mental workload and acceptance.
AB  - New driver support systems are developed and introduced to the market at
      increasing speed. In conditions of traffic congestion drivers may be supported by
      a "Congestion Assistant", a system that combines the features of a Congestion
      Warning System (acoustic warning and gas pedal counterforce) and a Stop & Go
      system (automatic gas and brake pedal during congestion). To gain understanding
      of the effects of driving with a Congestion Assistant on drivers, mental workload
      of drivers was registered under different conditions as well as acceptance of the
      system. Mental workload was measured by means of physiological registrations,
      i.e. heart rate, a secondary task and with the aid of subjective scaling
      techniques. Acceptance was measured with an acceptance scale. The study was
      carried out in an advanced driving simulator. Driving with the Congestion
      Assistant while in congestion potentially leads to decreased driver mental
      workload, whereas just before congestion starts, i.e. developing just noticeable,
      the system may add to the workload of the driver. Acceptance is generally high
      after experiencing the system, though not in all respects.

PMID- 18823876
TI  - Drinking without thinking: an implicit measure of alcohol motivation predicts
      failure to control alcohol use.
AB  - Addiction is characterized by dyscontrol - substance use despite intentions to
      restrain. Using a sample of at-risk drinkers, the present study examined whether
      an implicit measure of alcohol motivation (the Implicit Association Test [IAT];
      Greenwald, A.G., McGhee, D.E., & Schwartz, J.L.K. (1998). Measuring individual
      differences in implicit cognition: the Implicit Association Test. Journal of
      Personality and Social Psychology, 74, 1464-1480) would predict dyscontrol of
      alcohol use. Participants completed an IAT and, to elicit motivation to restrain
      alcohol use, were instructed that greater consumption in a taste test would
      impair performance on a later task for which they could win a prize. All
      participants viewed aversive slides and then completed a thought-listing task.
      Participants either exerted self-control by suppressing negative affect and
      thoughts regarding the slides or did not exert self-control. Post-manipulation,
      the groups did not differ in mood, urge to drink or motivation to restrain
      consumption. During the subsequent taste test, participants whose self-control
      resources were depleted consumed more alcohol than did those in the control
      group. Additionally, the IAT, but not an explicit measure of alcohol motivation,
      more strongly predicted alcohol use when self-control resources were depleted.
      The results indicate that the IAT may have utility in predicting dyscontrolled
      alcohol use.

PMID- 18823877
TI  - Forkhead box, class O transcription factors in brain: regulation and behavioral
      manifestation.
AB  - BACKGROUND: The mammalian forkhead box, class O (FoxO) transcription factors
      function to regulate diverse physiological processes. Emerging evidence that both
      brain-derived neurotrophic factor (BDNF) and lithium suppress FoxO activity
      suggests a potential role of FoxOs in regulating mood-relevant behavior. Here, we
      investigated whether brain FoxO1 and FoxO3a can be regulated by serotonin and
      antidepressant treatment and whether their genetic deletion affects behaviors.
      METHODS: C57BL/6 mice were treated with D-fenfluramine to increase brain
      serotonergic activity or with the antidepressant imipramine. The functional
      status of brain FoxO1 and FoxO3a was audited by immunoblot analysis for
      phosphorylation and subcellular localization. The behavioral manifestations in
      FoxO1- and FoxO3a-deficient mice were assessed via the Elevated Plus Maze Test,
      Forced Swim Test, Tail Suspension Test, and Open Field Test. RESULTS: Increasing
      serotonergic activity by d-fenfluramine strongly increased phosphorylation of
      FoxO1 and FoxO3a in several brain regions and reduced nuclear FoxO1 and FoxO3a.
      The effect of D-fenfluramine was mediated by the phosphatidylinositol 3-kinase
      (PI3K)/Akt signaling pathway. Chronic, but not acute, treatment with the
      antidepressant imipramine also increased the phosphorylation of brain FoxO1 and
      FoxO3a. When FoxO1 was selectively deleted from brain, mice displayed reduced
      anxiety. In contrast, FoxO3a-deficient mice presented with a significant
      antidepressant-like behavior. CONCLUSIONS: FoxOs may be a transcriptional target
      for anxiety and mood disorder treatment. Despite their physical and functional
      relatedness, FoxO1 and FoxO3a influence distinct behavioral processes linked to
      anxiety and depression. Findings in this study reveal important new roles of
      FoxOs in brain and provide a molecular framework for further investigation of how
      FoxOs may govern mood and anxiety disorders.

PMID- 18823878
TI  - The nonhuman primate amygdala is necessary for the acquisition but not the
      retention of fear-potentiated startle.
AB  - BACKGROUND: In a previous study, we found that rhesus monkeys prepared with
      bilateral lesions of the amygdala failed to acquire fear-potentiated startle to a
      visual cue. However, a second group of monkeys, which received the lesion after
      training, successfully demonstrated fear-potentiated startle learned prior to the
      lesion. METHODS: In the current experiment, the eight monkeys used in the second
      part of the original study, four of which had bilateral amygdala lesions and the
      four control animals, were trained using an auditory cue and tested in the fear
      potentiated startle paradigm. This test was performed to determine whether they
      could acquire fear-potentiated startle to a new cue. RESULTS: Monkeys with
      essentially complete damage to the amygdala (based on histological analysis) that
      had retained and expressed fear-potentiated startle to a visual cue learned
      before the lesion failed to acquire fear-potentiated startle to an auditory cue
      when training occurred after the lesion. CONCLUSIONS: The results suggest that
      while the nonhuman primate amygdala is essential for the initial acquisition of
      fear conditioning, it does not appear to be necessary for the memory and
      expression of conditioned fear. These findings are discussed in relation to a
      network of connections between the amygdala and the orbitofrontal cortex that may
      subserve different component processes of fear conditioning.

PMID- 18823879
TI  - Neurophysiological correlates of borderline personality disorder: a transcranial
      magnetic stimulation study.
AB  - BACKGROUND: Cortical inhibition deficits have been demonstrated in several
      disorders with deficits in impulsive control (e.g., attention
      deficit/hyperactivity disorder [ADHD], tic disorder, Tourette syndrome) by using
      transcranial magnetic stimulation (TMS). With borderline personality disorder
      (BPD), we investigated another disorder associated with high impulsivity by TMS.
      We hypothesized that BPD patients display decreased cortical inhibition and/or
      increased cortical excitation as assessed with TMS. METHODS: Different inhibitory
      and excitatory TMS parameters were investigated in 19 unmedicated female BPD
      patients and 19 healthy control subjects matched for sex, age, handedness, and
      body height. Additionally, the results were controlled for ADHD symptomatology.
      RESULTS: A reduced cortical silent period (CSP) duration was found in BPD
      patients compared with healthy control subjects in the right cortex. Even after
      controlling for ADHD symptoms, this result remained significant. CONCLUSIONS:
      These findings support an association between BPD and cortical inhibition
      deficits as indexed through TMS. The results are discussed considering basic
      neurobiological mechanisms that may explain our findings of decreased
      intracortical inhibition in BPD patients.

PMID- 18823880
TI  - Impairment of working memory maintenance and response in schizophrenia:
      functional magnetic resonance imaging evidence.
AB  - BACKGROUND: Comparing prefrontal cortical activity during particular phases of
      working memory in healthy subjects and individuals diagnosed with schizophrenia
      might help to define the phase-specific deficits in cortical function that
      contribute to cognitive impairments associated with schizophrenia. This study
      featured a spatial working memory task, similar to that used in nonhuman
      primates, that was designed to facilitate separating brain activation into
      encoding, maintenance, and response phases. METHODS: Fourteen patients with
      schizophrenia (4 medication-free) and 12 healthy comparison participants
      completed functional magnetic resonance imaging while performing a spatial
      working memory task with two levels of memory load. RESULTS: Task accuracy was
      similar in patients and healthy participants. However, patients showed reductions
      in brain activation during maintenance and response phases but not during the
      encoding phase. The reduced prefrontal activity during the maintenance phase of
      working memory was attributed to a greater rate of decay of prefrontal activity
      over time in patients. Cortical deficits in patients did not appear to be related
      to antipsychotic treatment. In patients and in healthy subjects, the time
      dependent reduction in prefrontal activity during working memory maintenance
      correlated with poorer performance on the memory task. CONCLUSIONS: Overall,
      these data highlight that basic research insights into the distinct
      neurobiologies of the maintenance and response phases of working memory are of
      potential importance for understanding the neurobiology of cognitive impairment
      in schizophrenia and advancing its treatment.

PMID- 18823881
TI  - Polarized light-stimulated enzymatic hydrolysis of chitin and chitosan.
AB  - Illumination with white linearly polarized light (WLPL) stimulated chitinase and
      chitosanase in their degradation of chitin and chitosan, respectively. Enzymes
      were illuminated at room temperature in separate vessels, then admixed in
      reactors containing polysaccharides. Hydrolysis of chitosan to glucosamine
      followed first order kinetics whereas hydrolysis of chitin to N-acetylglucosamine
      deviated from the first order kinetics. In both cases, an increase in the rate of
      hydrolysis depended on the illumination time. Efficient degradation required up
      to 60 min exposure of the enzyme to WLPL.

PMID- 18823882
TI  - Screening of knee-joint vibroarthrographic signals using the strict 2-surface
      proximal classifier and genetic algorithm.
AB  - We propose the strict 2-surface proximal (S2SP) classifier, by seeking two cross
      proximal planes to fit the distribution of the given samples in a corresponding
      feature space. The method is applied to screen knee-joint vibration or
      vibroarthrographic (VAG) signals based on statistical parameters derived from
      signals and selected by the genetic algorithm. A database of 89 VAG signals was
      studied. With the leave-one-out procedure, the linear S2SP classifier provided an
      efficiency of 0.82 in terms of the area under the receiver operating
      characteristics curve (A(z)); the nonlinear S2SP classifier provided 0.95 in A(z)
      value using the Gaussian kernel, and possessed good robustness around the
      selected kernel parameter.

PMID- 18823883
TI  - Fifteen-year trend in the use of reproductive surgery in women in the United
      States.
AB  - OBJECTIVE: To determine trends in female reproductive surgery volume. DESIGN:
      Database analysis using the Healthcare Cost and Utilization Project databases
      from 1988, 1992, 1998, and 2002. SETTING: Academic medical center. PATIENT(S):
      All patients who underwent reproductive surgeries using United States community
      hospital discharge data and inpatient and outpatient data for New Jersey (NJ) and
      Maryland (MD). INTERVENTION(S): SAS statistical software was used to estimate the
      number of reproductive surgeries per year; weighted least squares analysis was
      performed to estimate trends in surgeries. MAIN OUTCOME MEASURE(S): Number of
      reproductive surgeries. RESULT(S): Nationally, approximately 250,000 inpatient
      female reproductive surgeries are performed yearly. There was a modest decreasing
      trend (-17%) in total reproductive surgeries, and the number of procedures with
      an associated diagnosis of infertility declined 79%; neither change reached
      statistical significance. Alternatively, a significant decline occurred in
      surgeries of the fallopian tubes and ovaries. Likewise, inpatient surgeries were
      unchanged in NJ and actually increased in MD (+13%), although outpatient
      surgeries declined in both states (-12% and -37%, respectively). CONCLUSION(S):
      The increased use of assisted reproductive technology (ART) has coincided with a
      decrease in surgeries on the fallopian tubes and ovaries. With the exception of
      surgery for tubal infertility, reproductive surgery has largely been
      complementary to, rather than replaced by, ART.

PMID- 18823884
TI  - Increased sperm chromatin decondensation in selected nonapoptotic spermatozoa of
      patients with male infertility.
AB  - OBJECTIVE: To evaluate the sperm chromatin decondensation (SCD) rates of the
      annexin-negative (nonapoptotic) sperm fraction of patients with infertility using
      hamster intracytoplasmic sperm injection (H-ICSI). In healthy donors, the
      depletion of apoptotic sperm using annexin V-based magnetic-activated cell
      separation (MACS) enhances hamster oocyte sperm penetration but does not increase
      SCD rates following H-ICSI. DESIGN: A prospective-controlled study. SETTING: Male
      infertility clinic, European Academy of Andrology Center Leipzig. PATIENT(S):
      Twenty-one male infertility patients with subnormal spermiogram. INTERVENTION(S):
      Spermatozoa were separated by Annexin V-MACS. MAIN OUTCOME MEASURE(S): Apoptosis
      signaling (disruption of transmembrane mitochondrial potential, transmembrane
      mitochondrial potential [TMP], and activation of caspases-3 [CP3]) and SCD rates
      of human spermatozoa after hamster intracytoplasmic sperm injection. RESULT(S):
      Infertility patients showed high levels of sperm with active CP3 and disrupted
      TMP, which correlated negatively with SCD rates. Annexin V-MACS resulted in a
      significant enrichment of spermatozoa with inactive CP3 and intact TMP in the
      annexin-negative fraction. Similarly, annexin-negative sperm had the highest SCD
      rates following H-ICSI compared with controls and annexin-positive sperm.
      CONCLUSION(S): These results suggest that nonapoptotic spermatozoa prepared by
      annexin V-MACS display higher early fertilization potential following ICSI. The
      technique should be evaluated in a clinical setting for its impact on ICSI
      outcomes in patients diagnosed with infertility.

PMID- 18823885
TI  - Effects of adding small amounts of oxygen to a carbon dioxide-pneumoperitoneum of
      increasing pressure in rabbit ventilation models.
AB  - OBJECTIVE: To evaluate the metabolic consequences of the addition of oxygen to
      the CO(2)-pneumoperitoneum. DESIGN: Prospective randomized study in rabbits.
      After 30 minutes of ventilation pneumoperitoneum was maintained for 90 minutes
      with pure CO(2) or CO(2) with 2% or 6% of oxygen. The intraperitoneal pressure
      was increased from 10 to 15 and 20 mm Hg every 30 minutes. Ventilation rate was
      either fixed or a progressive hyperventilation. End points were changes in
      arterial blood gases (Pco(2), Po(2)), pH, acid-base balance (actual base excess
      [ABE], standard bicarbonate [SBC], standard base excess [SBE], hydrogen carbonate
      [HCO(3)(-)], concentration of total carbon dioxide [Tco(2)]); oxygen and oximetry
      (oxyhemoglobin [O(2)Hb], oxygen saturation [So(2)], reduced hemoglobin [RHb],
      total oxygen concentration [To(2)], and oxygen tension at half saturation
      assessing hemoglobin oxygen affinity [p50]); and lactate concentrations assayed
      every 15 minutes. SETTING: University research center. ANIMALS: Twenty-four adult
      female New Zealand white rabbits. INTERVENTION(S): Anesthesia, mechanical
      ventilation, and pneumoperitoneum. RESULT(S): The effects of CO(2)
      pneumoperitoneum on all end points increased with the elevated intraperitoneal
      pressure and were more pronounced when ventilation was fixed. Changes were less
      when 2% or 6% of oxygen had been added to the CO(2)-pneumoperitoneum. With use of
      logistic regression, the addition of oxygen, intraperitoneal pressure, and
      ventilation were found to be independent variables affecting Pco(2), pH, ABE,
      SBE, HCO(3)(-), O(2)Hb, So(2), p50, and end-tidal CO(2). CONCLUSION(S): The
      metabolic consequences of the combined effect of increased intraperitoneal
      pressure and CO(2)-pneumoperitoneum were less when 2% to 6% of oxygen was added
      or when animals were hyperventilated. We suggest that metabolic and mesothelial
      hypoxemia caused by CO(2) absorption can be reduced by adding small amounts of
      oxygen and by hyperventilation.

PMID- 18823886
TI  - Association of circulating matrix metalloproteinase-1, but not adiponectin, with
      advanced coronary artery disease.
AB  - OBJECTIVE: Recent evidence suggests that high tissue matrix metalloproteinase-1
      (MMP-1) and low adiponectin may serve as biomarkers of atherosclerosis. Results
      on the associations of circulating MMP-1 and adiponectin concentrations are
      scarce. We hypothesized that patients with multivessel coronary artery disease
      (CAD) have elevated high-sensitivity C-reactive protein (hs-CRP), MMP-1 but low
      adiponectin levels, and concomitant measurements of these biomarkers could
      improve predictive strength for advanced CAD. RESEARCH DESIGN AND METHODS: We
      analyzed concentrations of MMP-1, hs-CRP and adiponectin in 217 subjects with
      angiographically documented multivessel CAD (two-, or three-vessel disease by
      luminal stenosis >or=50%) and 81 controls. MMP-1 and hs-CRP were notably higher
      in patients with CAD; while adiponectin was not significantly different between
      two groups. Levels of hs-CRP positively correlated with body mass index and left
      ventricular dysfunction (R(2)=0.16, P<0.0001); while adiponectin was
      significantly associated with age, gender, and levels of cholesterol and
      triglyceride (R(2)=0.09, P<0.0001). On the contrary, MMP-1 was not associated
      with any clinical cardiovascular risk factors, and still an independent predictor
      (OR=1.49, P<0.0001) of multivessel CAD after the adjustment of clinical risk
      factors and hs-CRP. CONCLUSION: Elevated MMP-1 and hs-CRP, but not low
      adiponectin concentrations, could predict the presence of advanced coronary
      atherosclerosis. In addition, MMP-1 may serve as a more specific marker for
      significant CAD independent of hs-CRP.

PMID- 18823887
TI  - Apolipoprotein CI levels are associated with atherosclerosis in men with the
      metabolic syndrome and systemic inflammation.

PMID- 18823888
TI  - Large variations in absolute wall shear stress levels within one species and
      between species.

PMID- 18823889
TI  - Predictive value of coronary artery stenoses and C-reactive protein levels in
      patients with stable coronary artery disease.
AB  - INTRODUCTION AND AIMS: Coronary occlusions resulting in acute events often occur
      at the site of non-severe stenoses. We sought to assess the prognostic value of
      non-obstructive coronary stenoses and C-reactive protein (CRP) levels in patients
      with chronic stable angina (CSA). METHODS: We studied 790 consecutive patients
      with CSA who underwent routine coronary arteriography. High sensitivity CRP and
      coronary angiograms were assessed at study entry. Angiographic coronary disease
      severity was graded using a "vessel score" (number of coronary arteries showing
      at least 50% reduction in lumen diameter) and extent of disease with an
      "extension score" (proportion of the coronary artery tree showing
      angiographically detectable atheroma). Patients were followed up for 1 year.
      RESULTS: Significant left main stem disease was present in 54 patients (6.8%).
      368 patients (46.6%) underwent revascularization. 71 patients (9%) had at least
      one of the events comprised in the combined study end-point (unstable angina,
      myocardial infarction (AMI) and cardiac death). Patients who suffered cardiac
      adverse events had a significantly higher vessel score (n) (2.0 [2.0-3.0] vs. 2.0
      [1.0-2.0], P<0.001), extension score (%) (23.5 [17-34.5] vs. 16.0 [6.0-27.0],
      P<0.001) and CRP levels (mg/L) (3.0 [1.8-7.2] vs. 2.3 [1.1-4.7], P=0.001)
      compared to patients without events. Age, previous history of AMI, vessel score,
      extension score and CRP levels were significantly associated with the study end
      point. Multivariate analysis showed extension score (OR 5.3 [2.8-10.3] CI 95%;
      P<0.001), revascularization (OR 0.26 [0.14-0.48] CI 95%; P<0.001) and CRP levels
      (OR 1.9 [1.1-3.2] CI 95%; P=0.03), but not vessel score (P=0.1), to be
      independent predictors of the combined end-point. CONCLUSIONS: In patients with
      CSA, independently of revascularization, extension score and CRP levels predict
      cardiac adverse events, regardless of the presence or absence of flow limiting
      coronary lesions.

PMID- 18823890
TI  - The kynurenines are associated with oxidative stress, inflammation and the
      prevalence of cardiovascular disease in patients with end-stage renal disease.
AB  - Increased oxidative stress (SOX), inflammation and prevalence of cardiovascular
      disease (CVD) have been reported in end-stage renal disease (ESRD), but their
      associations with kynurenine (KYN) pathway activation remain unknown. We
      determined the plasma concentrations of tryptophan (TRP), KYN, 3
      hydroxykynurenine (3-HKYN); two distinct SOX markers: Cu/Zn superoxide dismutase
      (Cu/Zn SOD) and total peroxide; and high sensitivity C-reactive protein (hs CRP)
      as a indicator of inflammation in 146 ESRD patients and healthy controls.
      Analysis of TRP degradation through the KYN pathway demonstrated that in uremia
      the concentrations of this aminoacid were decreased by 40-60% in comparison with
      controls. In contrast, the plasma levels of KYN and 3-HKYN in ESRD patients were
      increased by 32-96% and 184-306%, respectively. These changes were accompanied by
      significant increase in the kyn/trp ratios by 140-240%, and 3-hkyn/kyn ratios by
      40-154% in uremics compared to controls. ESRD patients showed a significant
      increase in Cu/Zn SOD, total peroxide and hs CRP levels between controls and all
      patients group. KYN and 3-HKYN were positively associated with inflammation and
      SOX markers in uremics. Logistic regression analysis showed that age, gender,
      presence of DM (all p<0.001), elevated hs CRP (p<0.01) and 3-HKYN levels (p<0.05)
      were independently associated with the presence of CVD in this population. These
      results suggest a relationship between KYN pathway activation and increased SOX,
      inflammation and CVD prevalence in ESRD patients.

PMID- 18823891
TI  - Validation of a liquid chromatography-tandem mass spectrometry method to enable
      quantification of 3-iodothyronamine from serum.
AB  - There is great interest lately in the availability of analytical methods for
      quantification of 3-iodothyronamine from blood and tissues. To date, no validated
      method for determination of 3-iodothyronamine from biological matrices has been
      described. Detailed in this report is an LC-MS/MS method that permits accurate
      and reproducible quantification of pharmacological concentrations of 3
      iodothyronamine from rat serum, with a 0.0008 M lower limit of quantification.
      Endogenous 3-iodothyronamine was observed from rodent and human serum (0.2 mL) at
      the method limit of detection. In summary, the LC-MS/MS method enables
      quantification of circulating 3-iodothyronamine to allow examination of a
      relationship with biological activity.

PMID- 18823892
TI  - Preparation of a sulfoxide group and ammonium-salt bonded silica stationary phase
      for separation of polychlorinated biphenyls from mineral oils.
AB  - In this study, a silica stationary phase modified with sulfoxide group and
      ammonium-salt was prepared for the separation of polychlorinated biphenyls (PCBs)
      from mineral oils, and its properties were investigated. Organic sulfide was
      attached to a diamino (primary and secondary amino) bonded silica surface by an
      amide bond, and the bonded sulfide groups were oxidized with periodate to afford
      sulfoxide groups bonded to the stationary phase. The secondary amino groups in
      the spacer chain were converted to ammonium-salt by the addition of hydrochloric
      acid. The sulfoxide group and ammonium-salt bonded stationary phase was tested
      for their suitability as adsorbent for SPE-type preparative short columns and for
      an analytical HPLC-type separation. The new stationary phase (1.2 mmol of sulfur
      bonded per gram) separated PCBs from mineral oils (paraffin-based transformer
      oils) more efficiently than previously reported stationary phases including
      sulfoxide group or ammonium-salt bonded ones. The quantitative chromatographic
      parameters for an aliphatic hydrocarbon (eicosane) and some PCB congeners also
      indicated strong retention of highly chlorinated biphenyls by the sulfoxide and
      ammonium-salt bonded silica compared with simple aminopropyl, sulfoxide group or
      ammonium-salt bonded ones. A cleanup procedure was established for simple
      determination of PCBs in mineral oil samples using sulfoxide group and ammonium
      salt bonded silica packed column fractionation. The analytical method,
      combination of the cleanup procedure, and measurement with a GC-high resolution
      (magnetic sector) MS or a GC-quadrupole MS were validated using mineral oil
      certified reference materials.

PMID- 18823893
TI  - Mercury speciation and analysis in drinking water by stir bar sorptive extraction
      with in situ propyl derivatization and thermal desorption-gas chromatography-mass
      spectrometry.
AB  - A method for mercury analysis and speciation in drinking water was developed,
      which involved stir bar sorptive extraction (SBSE) with in situ propyl
      derivatization and thermal desorption (TD)-GC-MS. Ten millilitre of tap water or
      bottled water was used. After a stir bar, pH adjustment agent and derivatization
      reagent were added, SBSE was performed. Then, the stir bar was subjected to TD-GC
      MS. The detection limits were 0.01 ng mL(-1) (ethylmercury; EtHg), 0.02 ng mL(-1)
      (methylmercury; MeHg), and 0.2 ng mL(-1) (Hg(II) and diethylmercury (DiEtHg)).
      The method showed good linearity and correlation coefficients. The average
      recoveries of mercury species (n=5) in water samples spiked with 0.5, 2.0, and
      6.0 ng mL(-1) mercury species were 93.1-131.1% (RSD<11.5%), 90.1-106.4%
      (RSD<7.8%), and 94.2-109.6% (RSD<8.8%), respectively. The method enables the
      precise determination of standards and can be applied to the determination of
      mercury species in water samples.

PMID- 18823894
TI  - Multi-residue analysis of steroids at sub-ng/L levels in surface and ground
      waters using liquid chromatography coupled to tandem mass spectrometry.
AB  - Most analytical methodologies currently available for the determination of
      steroids in water only identify a few representative compounds (mainly
      estrogens). In this context, a multi-residue methodology based on liquid
      chromatography-tandem mass spectrometry was developed for the determination of 26
      steroids including natural and synthetic estrogens, progestagens and androgens.
      The method described involves limited sample preparation as it includes a
      filtration followed by a single solid-phase extraction step using a C18
      cartridge. The analytical procedure allows the determination of the target
      analytes in the lower ng/L range, with recoveries above 80%. The methodology was
      successfully applied to the analysis of steroids in several surface and ground
      waters. In all the waters, estrogens, androgens and/or progestagens were
      determined.

PMID- 18823895
TI  - Simultaneous liquid-liquid microextraction/methylation for the determination of
      haloacetic acids in drinking waters by headspace gas chromatography.
AB  - A novel analytical method that combines simultaneous liquid-liquid
      microextraction/methylation and headspace gas chromatography-mass spectrometry
      for the determination of nine haloacetic acids (HAAs) in water was reported. A
      mechanistic model on the basis of mass transfer with chemical reaction in which
      methylation of HAAs was accomplished in n-pentane-water (150 microl-10 ml) two
      phase system with a tetrabutylammonium salt as phase transfer catalyst was
      proposed. Derivatisation with dimethylsulphate was completed in 3 min by shaking
      at room temperature. The methyl ester derivatives and the organic phase were
      completely volatilised by static headspace technique, being the gaseous phase
      analysed. Parameters related to the extraction/methylation and headspace
      generation of HAAs were studied and the results were compared with methyl
      haloacetate standards to establish the yield of each step. The thermal
      instability of HAAs, by degradation to their respective halogenated hydrocarbon
      by decarboxylation, and the possible hydrolysation of the methyl esters were
      rigorously controlled in the whole process to obtain a reliable and robust
      method. The proposed method yielded detection limits very low which ranges from
      0.02 to 0.4 microg l(-1) and a relative standard deviation of ca. 7.5%. Finally,
      the method was validated with the US Environmental Protection Agency (EPA) method
      552.2 for the analysis of HAAs in drinking and swimming pool water samples
      containing concentrations of HAAs that must be higher than 10 microg l(-1) due to
      the fact that this method is less sensitive than the proposed one.

PMID- 18823896
TI  - Development of an immunoaffinity column method using broad-specificity monoclonal
      antibodies for simultaneous extraction and cleanup of quinolone and sulfonamide
      antibiotics in animal muscle tissues.
AB  - This paper describes a novel mixed-bed immunoaffinity column (IAC) method. The
      IAC was produced by coupling anti-quinolone and anti-sulfonamide broad
      specificity monoclonal antibodies to Sepharose 4B for simultaneously isolating 13
      quinolones (QNs) and 6 sulfonamides (SAs) from swine and chicken muscle tissues,
      followed by antibiotic determination using liquid chromatography-tandem mass
      spectrometry (LC-MS/MS). A new broad-specificity Mab (B1A4E8) toward sulfonamides
      was produced using sulfamethoxazole as hapten that demonstrated cross
      reactivities to 6 SAs in the range of 31-112%. IAC optimized conditions were
      found that allowed the IAC to be reused for selective binding of both SAs and
      QNs. Recoveries of all 19 antibiotics from animal muscle ranged from 72.6 to
      107.6%, with RSDs below 11.3% and 15.4% for intra-day and inter-day experiments,
      respectively. The limit of quantification ranged from 0.5 to 3.0ng/g. The
      strategy used here for a mixed-bed IAC may be used to study other compounds and
      more than two classes of analytes simultaneously.

PMID- 18823897
TI  - Fingerprint analysis of thermolytic decarboxylation of tryptophan to tryptamine
      catalyzed by natural oils.
AB  - A number of N,N-dialkylated tryptamines show psychoactive properties in man which
      resulted in a renewed interest in psychopharmacological research. Attempts to
      manufacture these derivatives are increasing within a clandestine environment,
      where literature procedures are adapted and information is exchanged on the
      Internet. One such example is based on the thermolytic decarboxylation of
      tryptophan to tryptamine as the precursor to psychoactive derivatives. This
      procedure was proposed to make use of household solvents such as turpentine
      substitute and white spirit to facilitate decarboxylation. Discussions on
      websites also suggested the catalytic use of natural oils in order to accelerate
      these reactions. In this research, the analytical characterization of this
      preparation procedure was carried out using gas chromatography-ion trap single
      and tandem stage mass spectrometry in electron and chemical ionization mode that
      led to the identification of previously unreported 1-mono and 1,1-disubstituted
      tetrahydro-beta-carboline (THBCs) by-products. The tryptamine product and several
      THBC by-products were determined quantitatively and a "fingerprint" analysis of
      the crude products allowed for the differentiation between the essential oil
      catalysts involved as indicated by the presence of tetrahydro-beta-carbolines and
      their imine intermediates.

PMID- 18823898
TI  - Determination of carbamate, phenylurea and phenoxy acid herbicide residues by gas
      chromatography after potassium tert-butoxide/dimethyl sulphoxide/ethyl iodide
      derivatization reaction.
AB  - The usefulness of the potassium tert-butoxide/dimethyl sulphoxide/ethyl iodide
      reaction with carbamate and phenylurea herbicides, and its application to phenoxy
      acids as a way to prevent hazards and toxicity of the sodium hydride/dimethyl
      sulphoxide/methyl iodide reaction was studied. Using factorial design
      optimization of this reaction was carried out. A solid-phase extraction method
      using dimethyl sulphoxide as eluent on-line with this reaction was developed to
      determine these herbicides in water samples by gas chromatography-mass
      spectrometry. Relative standard deviation values were lower than 10% for most of
      the herbicides in multicomponent trace determinations. Detection limits were in
      the 0.110-0.652 ng L(-1) concentration range. The validity of the method was
      confirmed by recovery studies from natural water samples.

PMID- 18823899
TI  - Development of a rapid method to determine phenolic and other polar compounds in
      walnut by capillary electrophoresis-electrospray ionization time-of-flight mass
      spectrometry.
AB  - The aim of this work was to develop a capillary electrophoresis-mass spectrometry
      (CE-MS) method to identify and quantify phenolic and other related polar
      compounds in walnut samples. The extraction capacity of several solvent mixtures
      of phenolic compounds from walnut by conventional solid-liquid extractions was
      tested, and CE and electrospray ionization MS parameters were optimized. The
      finalized procedure is able to determine many well-known phenolic compounds
      present in walnuts and provide relevant information about the presence of minor
      polar compounds. A new compound in walnut ((2E,4E)-8-hydroxy-2,7-dimethyl-2,4
      decadiene-1,10-dioic acid 6-O-beta-d-glucopiranosyl ester, [M-H](-) 403.161m/z)
      with a structure similar to glansreginins was also identified. Phenolic compounds
      correspond to 14-28% of total polar compounds quantified. Aglycone and
      glycosylated ellagic acid represent the principal components and account for 64
      75% of total phenols in walnuts. However, the sum of glansreginins A, B and
      (2E,4E)-8-hydroxy-2,7-dimethyl-2,4-decadiene-1,10-dioic acid 6'-O-beta-d
      glucopiranosyl ester was in the range of 72-86% of total quantified compounds. In
      addition, this is the first time that separation by CE with detection by
      electrospray ionization time-of-flight MS has been applied to the analysis of
      phenolic and other polar compounds in walnut samples, providing results in less
      than 15min.

PMID- 18823900
TI  - Rheological properties of colloidal gels formed from fumed silica suspensions in
      the presence of cationic surfactants.
AB  - Rheological responses of colloidal gels formed from fumed silica suspensions in
      aqueous KOH solution at pH 11 by the addition of cationic surfactants, such as
      dodecyltrimethylammonium chloride (C12 TAC) and hexadodecyltrimethylammonium
      chloride (C16 TAC) have been investigated as functions of silica and surfactant
      concentrations. Stable and aggregated fumed silica suspensions with negative
      charges cause gelling by adding the cationic surfactants through electrical
      neutralization of their micelles. The resulting critical strain and storage
      modulus of the gelled silica suspension increase with an increase in the
      surfactant concentration, irrespective of the cationic surfactant. This means
      that the higher the surfactant concentration is, the more effective the
      electrical neutralization interaction through the micelle of the cationic
      surfactant is. Moreover, the resulting gels can be classified into the strong
      link gel and the weak-link one in the presence of C12 TAC and C16 TAC,
      respectively, from a comparison of the silica volume fraction dependences of
      critical strain and storage modulus with the fractal gel model.

PMID- 18823901
TI  - Stabilization of nonaqueous foam with lamellar liquid crystal particles in
      diglycerol monolaurate/olive oil system.
AB  - Nonaqueous foams stabilized by lamellar liquid crystal (L alpha) dispersion in
      diglycerol monolaurate (designated as C12G2)/olive oil systems are presented.
      Foamability and foam stability depending on composition and the effects of added
      water on the nonaqueous foaming behavior were systematically studied. It was
      found that the foamability increases with increasing C12G2 concentration from 1
      to 3 wt% and then decreases with further increasing concentration, but the foam
      stability increases continuously with concentration. Depending on compositions,
      foams are stable for a few minutes to several hours. Foams produced by 10 wt%
      C12G2/olive oil system are stable for more than 6 h. In the study of effects of
      added water on the foaming properties of 5 wt% C12G2/olive oil system, it was
      found that the foamability and foam stability of 5 wt% C12G2/olive oil decreases
      upon addition of 1 wt% water, but with further increasing water, both the
      foamability and foam stability increase. Foams with 10% water added system are
      stable for approximately 4 h. Phase behavior study of the C12G2 in olive oil has
      shown the dispersion of L alpha particles in the dilute regions at 25 degrees C.
      Thus, stable foams in the C12G2/olive oil system can be attributed to L alpha
      particle, which adsorb at the gas-liquid interface as confirmed by surface
      tension measurements and optical microscopy. Laser diffraction particle size
      analyzer has shown that the average particle diameter decreases with increasing
      the C12G2 concentration and, hence, the foams are more stable at higher
      surfactant concentration. Judging from foaming test, optical micrographs, and
      particle size, it can be concluded that stable nonaqueous foams in the studied
      systems are mainly caused by the dispersion of L alpha particles and depending on
      the particle size the foam stability largely differs.

PMID- 18823902
TI  - Lymphoproliferative disease with features of lymphoma in the central nervous
      system of a horse.
AB  - Lymphoma (malignant lymphoma, lymphosarcoma) is uncommon in horses in the United
      Kingdom. This report describes an unusual form of lymphoproliferative disease
      with features of lymphoma restricted to the central nervous system (CNS) and with
      no evidence of a primary lesion elsewhere. Immunohistochemical examination
      defined an overwhelming predominance of T lymphocytes with admixed B lymphocytes
      and activated macrophages. This case exemplifies the challenges associated with
      definitive diagnosis of lymphoproliferative disease of the equine CNS.

PMID- 18823903
TI  - The journal of comparative pathology from 1943 to 2008.
AB  - The account of the Journal's first 53 years (Pattison, 1988), also reproduced in
      this issue, closed by noting the interruption of publication brought about by
      wartime exigencies and the death in 1941 of its founder and owner, Sir John
      McFadyean (Fig. 1). The present article considers the further development of the
      Journal from that time to the present day, a period of 65 years.

PMID- 18823904
TI  - Imitation of body postures and hand movements in children with specific language
      impairment.
AB  - Within the domain-general theory of language impairment, this study examined body
      posture and hand movement imitation in children with specific language impairment
      (SLI) and in their age-matched peers. Participants included 40 children with SLI
      (5 years 3 months to 6 years 10 months of age) and 40 children with typical
      language development (5 years 3 months to 6 years 7 months of age). Five tests
      were used to examine imitation and its underlying cognitive and motor skills such
      as kinesthesia, working memory, and gross motor coordination. It was hypothesized
      that children with SLI show a weakness in imitation of body postures and that
      this deficit is not equally influenced by the underlying cognitive and motor
      skills. There was a group effect in each cognitive and motor task, but only gross
      motor coordination proved to be a strong predictor of imitation in children with
      SLI. In contrast, hand movement imitation was strongly predicted by performance
      in the Kinesthesia task in typically developing children. Thus, the findings show
      not only that children with SLI performed more poorly on the imitation tasks than
      their typically developing peers but also that the groups' performances showed
      qualitative differences. The results of the current study provide additional
      support to the view that the weaknesses in children with SLI are not limited to
      the verbal domain.

PMID- 18823905
TI  - Mouse Dnmt3a preferentially methylates linker DNA and is inhibited by histone H1.
AB  - In mammals, DNA methylation is crucial for embryonic development and germ cell
      differentiation. The DNA methylation patterns are created by de novo-type DNA
      methyltransferases (Dnmts) 3a and 3b. Dnmt3a is crucial for global methylation,
      including that of imprinted genes in germ cells. In eukaryotic nuclei, genomic
      DNA is packaged into multinucleosomes with linker histone H1, which binds to core
      nucleosomes, simultaneously making contacts in the linker DNA that separates
      adjacent nucleosomes. In the present study, we prepared oligonucleosomes from
      HeLa nuclei with or without linker histone H1 and used them as a substrate for
      Dnmt3a. Removal of histone H1 enhanced the DNA methylation activity. Furthermore,
      Dnmt3a preferentially methylated the linker between the two nucleosome core
      regions of reconstituted dinucleosomes, and the binding of histone H1 inhibited
      the DNA methylation activity of Dnmt3a towards the linker DNA. Since an identical
      amount of histone H1 did not inhibit the activity towards naked DNA, the
      inhibitory effect of histone H1 was not on the Dnmt3a catalytic activity but on
      its preferential location in the linker DNA of the dinucleosomes. The central
      globular domain and C-terminal tail of the histone H1 molecule were indispensable
      for inhibition of the DNA methylation activity of Dnmt3a. We propose that the
      binding and release of histone H1 from the linker portion of chromatin may
      regulate the local DNA methylation of the genome by Dnmt3a, which is expressed
      ubiquitously in somatic cells in vivo.

PMID- 18823906
TI  - Application of ultrasound for bone age estimation in clinical practice.
AB  - OBJECTIVE: To assess the validity of bone age assessment by ultrasonography (US).
      STUDY DESIGN: Wrist US was performed on children (n = 100) undergoing
      radiographic bone age and compared with bone age estimation by a radiologist in
      the clinic and by endocrinologists under blinded conditions with Greulich and
      Pyle (GP) and Tanner and Whitehouse (TW3) methods. RESULTS: The strongest
      correlation (r(2)) was seen in the radiographic bone age assessment between the 2
      endocrinologists using the GP method (96.7%). The poorest correlation was seen
      when comparing radiographic methods to US of either wrist (74.6% to 82.6%). When
      bone age correlations were divided into normal, delayed or advanced, the highest
      correlation between the radiographic and US methods was found in the normal bone
      age group (80.9% to 86.1%) with weaker correlations for the delayed bone age
      group (77.1% to 86.9%) and the advanced bone age group (62.2% to 81.1%). US
      tended to overread delayed bone age and underread advanced bone age. US had poor
      positive and negative predictive value for identification of a normal or delayed
      bone age. The negative predictive value of US was 91% for an advanced bone age.
      CONCLUSIONS: On the basis of our data, US assessment should not yet be considered
      a valid replacement for radiographic bone age determination.

PMID- 18823907
TI  - Doctors likely to encounter children with musculoskeletal complaints have low
      confidence in their clinical skills.
AB  - OBJECTIVE: To assess self-rated confidence in pediatric musculoskeletal (pMSK)
      clinical assessment in trainees and experienced doctors in primary care and
      selected secondary care specialties to whom children with MSK problems are likely
      to present. STUDY DESIGN: Attendees at programmed postgraduate teaching sessions
      within a health care region of the United Kingdom completed an anonymous
      questionnaire to self-rate confidence in pMSK assessment compared with other
      bodily systems and describe exposure to MSK teaching. RESULTS: Respondents (n =
      346) were qualified from 23 different medical schools (United Kingdom and 9 non
      United Kingdom) and included trainees in Primary Care (n = 75), Pediatrics (n =
      39), Emergency (n = 39), Orthopedics (n = 40), and experienced doctors in Primary
      Care (n = 93), and Pediatrics (n = 60). Self-rated confidence in pMSK assessment
      was low; the majority had "no" or "some" confidence (21% and 53%, respectively).
      Conversely, most respondents were confident "in most aspects" or "very confident"
      for cardiovascular, respiratory, and abdominal systems. pMSK ranked lowest below
      all other systems. Most respondents (92%) recalled some teaching of adult MSK
      medicine, mostly at undergraduate level. Fewer (51%) recalled any teaching of
      pMSK medicine. CONCLUSIONS: Self-rated confidence in pMSK assessment was lowest,
      compared with other bodily systems, within doctors to whom children with MSK
      problems are likely to present. Core clinical skills are learnt at undergraduate
      level, and this study reflects poor levels of pMSK training which needs to be
      addressed.

PMID- 18823908
TI  - Early postnatal weight gain, intellectual performance, and body mass index at 7
      years of age in term infants with intrauterine growth restriction.
AB  - OBJECTIVE: To determine whether the postnatal growth rate of infants with
      intrauterine growth restriction (IUGR) is associated with later cognitive
      function and body mass index (BMI). STUDY DESIGN: Infants with IUGR (<2211 g at >
      or =37 weeks' gestation) were identified in data from the Collaborative Perinatal
      Project, excluding those with diagnoses affecting cognition or growth. Wechsler
      Scale of Children's Intelligence (WISC) scores at age 7 years and data on
      postnatal growth at 16 weeks were available for 463 infants with IUGR. Linear
      regression relating postnatal growth and WISC score, adjusting for potential
      confounders, was performed for these infants. BMI at 7 years also was examined.
      RESULTS: Weight gain at 16 postnatal weeks ranged from 1059 to 5119 g in the
      infants with IUGR, with lower achieved cognitive testing scores apparent at both
      extremes (ie, an inverted J-shape; P < .001). Infants gaining 1200 and 5000 g
      scored 15.5 and 2.4 fewer points, respectively, on the full scale compared with
      infants with score-maximizing growth. In contrast, BMI at 7 years was linearly
      related to postnatal weight gain (P < .001). CONCLUSIONS: Growth in the first 4
      postnatal months is an independent risk factor for cognitive outcome at age 7
      years, with both extremes associated with negative effects.

PMID- 18823909
TI  - Increased prevalence of renal and urinary tract anomalies in children with
      congenital hypothyroidism.
AB  - OBJECTIVE: We investigated the prevalence of congenital renal and urologic
      anomalies in children with congenital hypothyroidism to determine whether further
      renal and urologic investigations would be of benefit. STUDY DESIGN: Prevalence
      of congenital hypothyroidism was obtained from the New York State Congenital
      Malformation Registry. The occurrence of urinary tract anomalies were calculated
      for children with congenital hypothyroidism and compared to children without
      congenital hypothyroidism. In addition we obtained congenital hypothyroidism data
      from New York State newborn screening, and the cases were matched to Congenital
      Malformation Registry. RESULTS: Analysis of Congenital Malformation Registry data
      showed 980 children with congenital hypothyroidism and 3 661 585 children without
      congenital hypothyroidism born in New York State (1992-2005). Children with
      congenital hypothyroidism have a significantly increased risk of congenital renal
      and urological anomalies with the odds ratio (OR) of 13.2 (10.6-16.5). The other
      significantly increased defects in congenital hypothyroidism were cardiac,
      gastrointestinal, and skeletal. Analysis of matched data confirmed an increase of
      congenital renal and urologic anomalies with OR of 4.8 (3.7-6.3). CONCLUSIONS:
      Children with congenital hypothyroidism have an increased prevalence of
      congenital renal and urologic anomalies. We suggest that these children should be
      evaluated for the presence of congenital renal and urologic anomalies with renal
      ultrasonography, and that further studies of common genes involved in thyroid and
      kidney development are warranted.

PMID- 18823910
TI  - Addition of pH-impedance monitoring to standard pH monitoring increases the yield
      of symptom association analysis in infants and children with gastroesophageal
      reflux.
AB  - OBJECTIVE: To assess the additional yield of combined multichannel intraluminal
      pH-impedance (pH-MII) monitoring compared with standard pH monitoring on
      gastroesophageal reflux (GER) symptom associations in infants and children. STUDY
      DESIGN: In 80 patients, 24-hour ambulatory pH-MII monitoring was performed.
      Tracings were analyzed with established pH-MII criteria. Symptoms of
      regurgitation and belching were excluded from analysis, because these were
      considered to be a direct consequence of GER. Standard GER-symptom correlation
      indices were calculated with: 1) standard pH monitoring; 2) MII detection of
      liquid and mixed bolus GER; 3) MII detection of all bolus GER (liquid, mixed, and
      gas); 4) pH-MII detection of all GER, including pH-only GER. RESULTS: Fifty
      patients (21 children) were included. MII detection of all bolus GER yielded a
      significantly greater number of patients who were symptom-positive, 36 (72%)
      compared with 25 (50%) with standard pH-monitoring (P = .04). A positive symptom
      association was observed in 8 of 10 (80%) patients with pathological esophageal
      acid exposure and 28 of 40 (70%) patients with negative pH-findings. CONCLUSIONS:
      A high proportion of patients with normal esophageal acid exposure had a positive
      symptom association on pH-MII monitoring. Including all MII-detected bolus GER
      and excluding pH-only GER for analysis optimizes the yield of GER-symptom
      associations in infants and children.

PMID- 18823911
TI  - Respiratory pathogens in children with and without respiratory symptoms.
AB  - OBJECTIVES: To investigate the occurrence of respiratory pathogens in samples
      from children with and without respiratory symptoms and to identify whether age
      and/ or coinfections modify the impact of respiratory pathogens on symptoms.
      STUDY DESIGN: In a prospective longitudinal study, 18 children were sampled
      biweekly for respiratory pathogens, irrespective of respiratory symptoms.
      Polymerase chain reaction was performed for 13 respiratory pathogens. Episodes
      were defined "asymptomatic" if no symptoms of any respiratory tract illness were
      present between 1 week before and 1 week after sampling. RESULTS: A total of 230
      samples were collected. In 56% of the symptomatic episodes, a pathogen was
      detected, compared with 40% of the asymptomatic episodes (P = .03). Rhinovirus
      and coronaviruses were most prevalent in both symptomatic and asymptomatic
      episodes. In the youngest children, 9% of the pathogen-positive episodes were
      asymptomatic, compared with 36% in the oldest children (P = .01). Multiple
      pathogens were found in 17% of the symptomatic episodes and in 3% of the
      asymptomatic episodes (P = .02). CONCLUSIONS: Respiratory pathogens are
      frequently detected in samples from children with no respiratory symptoms.
      Symptomatic cases occurred more often in younger children and with detections of
      more than 1 respiratory pathogen.

PMID- 18823912
TI  - Effectiveness of a barcode medication administration system in reducing
      preventable adverse drug events in a neonatal intensive care unit: a prospective
      cohort study.
AB  - OBJECTIVE: Patients are at risk of harm from medication errors. Barcode
      medication administration (BCMA) systems are recommended to mitigate preventable
      adverse drug events (ADEs). Our hypothesis was that a BCMA system would reduce
      preventable ADEs by 45% in a neonatal intensive care unit. STUDY DESIGN: We
      conducted a prospective, observational, cohort study of a BCMA system
      intervention in a neonatal intensive care unit. Participants were admitted
      neonates during 50 weeks. Medication errors and potential or preventable ADEs
      were detected by a daily structured audit of each subject's medical record, with
      assignment of an event as a preventable ADE made by blinded assessors. The
      generalized estimating equation method was used in modeling the targeted,
      preventable ADE rate with covariates. RESULTS: A total of 92,398 medication doses
      were administered to 958 subjects. The generalized estimating equation method
      yielded a relative risk of preventable ADE when the system was implemented of
      0.53 (95% confidence limits 0.29 to 0.91, P = .04), adjusted for log(10)doses of
      medication/subject/day, a significant predictive covariate (P < .001), as well as
      for birth weight, sex, Caucasian race, birth cohort number, and nursing
      hours/subject/day. CONCLUSION: The BCMA system reduced the risk of targeted,
      preventable ADEs by 47%, controlling for the number of medication
      doses/subject/day, an important risk exposure.

PMID- 18823913
TI  - Parental assessments of internalizing and externalizing behavior and executive
      function in children with primary hypertension.
AB  - OBJECTIVE: To determine the relations between hypertension and parental ratings
      of behavior and executive functions in children with primary hypertension and to
      examine the potential moderating influence of obesity. STUDY DESIGN: Hypertensive
      and normotensive control groups were matched for age, sex, race, intelligence
      quotient, maternal education, household income, and obesity. Parents completed
      the Child Behavior Checklist to assess Internalizing and Externalizing problems
      and the Behavior Rating Inventory of Executive Function to assess behavioral
      correlates of executive function. RESULTS: Thirty-two hypertensive subjects and
      32 normotensive control subjects (aged 10 to 18 years) were enrolled. On the
      Child Behavior Checklist, hypertensives had higher Internalizing T-scores (53 vs
      44.5, P = .02) with 37% falling within the clinically significant range vs 6% of
      control subjects (P = .005). Internalizing score increased with increasing body
      mass index percentile in hypertensive but not normotensive subjects.
      Hypertensives had worse Behavior Rating Inventory of Executive Function Global
      Executive Composite T-scores compared with control subjects (50 vs 43, P = .009).
      CONCLUSIONS: Children with both hypertension and obesity demonstrate higher rates
      of clinically significant internalizing problems, and hypertensives (irrespective
      of obesity) demonstrate lower parental ratings of executive function compared
      with normotensive control subjects.

PMID- 18823914
TI  - Serum autoantibodies measured by immunofluorescence confirm a failure to
      differentiate PANDAS and Tourette syndrome from controls.
AB  - PANDAS and some cases of Tourette syndrome (TS) have been proposed to be post
      streptococcal movement disorders in which antibodies produced against group A
      beta-hemolytic streptococcus cross react against brain epitopes. Attempts to
      identify disease specific anti-striatal antibodies in the serum of affected
      patients have focused on the use of Western immunoblotting and ELISA
      methodologies. In this study, immunohistochemical techniques were used to
      identify serum anti-striatal antibody reactivity. In positive samples, double
      staining with anti-GFAP (glial) and anti-MAP2 (neuronal) was used to establish
      localization of the immunofluorescence. No significant differences in
      immunofluorescence or localization were identified in patients with PANDAS (n=30)
      and TS (n=30) as compared to controls (n=30). IF reactivity did not correlate
      with tic severity or elevated titers of antistreptococcal antibodies. Further
      comparisons showed no correlation between autoreactivity determined by
      immunofluorescence and the presence of previously measured immunoblot reactivity
      against human caudate or putative antigens (pyruvate kinase M1 and aldolase C).
      These results confirm an inability to distinguish patient populations by antibody
      measurements and raise further concerns about the presence of an autoimmune
      mechanism in PANDAS and TS.

PMID- 18823916
TI  - Re: A comparison of the incidence and location of positive surgical margins in
      robotic assisted laparoscopic radical prostatectomy and open retropubic radical
      prostatectomy: J. A. Smith, Jr., R. C. Chan, S. S. Chang, S. D. Herrell, P. E.
      Clark, R. Baumgartner and M. S. Cookson. J Urol 2007; 178: 2385-2390.

PMID- 18823917
TI  - Re: History of bacillus Calmette-Guerin and bladder cancer: an immunotherapy
      success story: H. W. Herr and A. Morales. J Urol 2008; 179: 53-56.

PMID- 18823919
TI  - Re: Oral ketoconazole for prevention of postoperative penile erection: a placebo
      controlled, randomized, double-blind trial: B. J. DeCastro, R. A. Costabile, L.
      P. McMann and A. C. Peterson. J Urol 2008; 179: 1930-1932.

PMID- 18823921
TI  - Diterpenoids from Jatropha multifida.
AB  - Chemical investigation on the stems of Jatropha multifida yielded two
      diterpenoids, multifolone and (4E)-jatrogrossidentadione acetate along with five
      known diterpenoids, a flavone and a coumarino-lignan. The structures of the
      compounds were settled by detailed analysis of their 1D and 2D NMR spectra. The X
      ray crystallographic analysis of (4E)-jatrogrossidentadione acetate was also
      accomplished.

PMID- 18823923
TI  - [Recovery from vascular aphasia: prognostic factors and evidence from functional
      brain imaging].
AB  - INTRODUCTION: Aphasia is a devastating language impairment resulting from
      acquired brain damage and resulting in severe communication handicap. Aphasia
      onset is generally followed by some degree of recovery. STATE OF ART: Prognosis
      of recovery is considered to depend upon a series of interacting neurobiological
      and individual factors. Prognosis is better determined based on neurobiological
      factors, whereas individual factors have a less predictable clinical outcome
      value. In addition, the results of recent functional neuro-imaging studies allow
      us to better understand the functional anatomy of the recovery from vascular
      aphasia. The neuro-imaging literature suggests that recovery from aphasia could
      depend upon right homologous to language areas, as well as on preserved
      perilesional left hemisphere regions. The role of either hemisphere seems to be
      modulated by time elapsed after brain damage, and language processing domain.
      Further, increasing evidence suggests that intensive and specific language
      therapy may interact with brain plasticity to promote recovery in chronic and
      severe aphasia. PERSPECTIVE AND CONCLUSION: A better understanding of the factors
      determining recovery from aphasia will contribute to optimizing intervention and,
      consequently improve the quality of life of people with aphasia.

PMID- 18823922
TI  - Hormonal regulation of oil accumulation in Brassica seeds: metabolism and
      biological activity of ABA, 7'-, 8'- and 9'-hydroxy ABA in microspore derived
      embryos of B. napus.
AB  - Developing seeds of Brassica napus contain significant levels of ABA and products
      of oxidation at the 7'- and 9'-methyl groups of ABA, 7'- and 9'-hydroxy ABA, as
      well stable products of oxidation of the 8'-methyl group, phaseic acid and
      dihydrophaseic acid. To probe the biological roles of the initially formed
      hydroxylated compounds, we have compared the effects of supplied ABA and the
      hydroxylated metabolites in regulating oil synthesis in microspore-derived
      embryos of B. napus, cv Hero that accumulate long chain fatty acids. Uptake into
      the embryos and metabolism of each of the hormone metabolites was studied by
      using deuterium labeled analogs. Supplied ABA, which was rapidly metabolized,
      induced expression of oleosin and fatty acid elongase genes and increased the
      accumulation of triacylglycerols and very long chain fatty acids. The metabolites
      7'- and 9'-hydroxy ABA had similar effects, with the 9'-hydroxy ABA having even
      greater activity than ABA. The principal catabolite of ABA, 8'-hydroxy ABA, also
      had hormonal activity and led to increased oil synthesis but induced the genes
      weakly. These results indicate that all compounds tested could be involved in
      lipid synthesis in B. napus, and may have hormonal roles in other ABA-regulated
      processes.

PMID- 18823924
TI  - Advanced post-processing for scanned ultrasonic arrays: application to defect
      detection and classification in non-destructive evaluation.
AB  - This paper describes a number of array post-processing methods developed for
      scanning applications in non-destructive evaluation. The approach is to capture
      and process the full matrix of all transmit-receive time-domain signals from the
      array. Post-processing the data in this way enables a multitude of imaging
      modalities to be implemented, including many that could not feasibly be achieved
      using conventional parallel firing techniques. The authors have previously
      published work on imaging algorithms for improving the characterisation of
      defects in solids by post-processing the data from a static linear ultrasonic
      array. These algorithms are extended and applied to data from a scanned array.
      This allows the effective aperture and range of probing angles to be increased,
      hence improving imaging and defect characterisation performance. Practical
      implementation issues such as scanning speed and data transfer are discussed.

PMID- 18823925
TI  - Role of class I human leukocyte antigen molecules in early steps of echovirus
      infection of rhabdomyosarcoma cells.
AB  - Several echoviruses use decay accelerating factor (DAF) as a cell surface
      receptor. However, most of them require additional cell surface coreceptors. We
      investigated the respective roles of DAF and class I human leukocyte antigen
      (HLA) molecules in the early steps of the echovirus 11 (EV11) lifecycle in
      rhabdomyosarcoma (RD) cells. EV11 infection was inhibited at an early stage by
      anti-beta2-microglobulin (beta2m) and anti-HLA monoclonal antibodies and by a
      soluble monochain HLA class I molecule. Expression of class I HLA molecules
      restored the early steps of the EV11 lifecycle, but its expression was not
      sufficient for EV11 replication and particle production. Expression of HLA class
      I molecules was associated with leukocyte cell line permissiveness to EV11
      infection. In conclusion, HLA class I molecules are involved in the early steps
      of EV11 infection of RD cells and appear to participate in a complex interplay of
      surface molecules acting as coreceptors, including DAF.

PMID- 18823926
TI  - Advanced treatment of the reverse osmosis concentrate produced during reclamation
      of municipal wastewater.
AB  - The work investigated the treatment of the concentrate produced from the reverse
      osmosis treatment of an MBR effluent. Two conventional chemical processes,
      coagulation and activated carbon adsorption, and three advanced oxidation
      processes (electrochemical treatment, photocatalysis and sonolysis) were applied.
      Coagulation with alum gave dissolved organic carbon (DOC) removals up to 42%,
      while FeCl(3) achieved higher removals (52%) at lower molar doses. Adsorption
      with granular activated carbon showed the highest DOC removals up to 91.3% for 5
      g/L. The adsorption isotherm was linear with a non-adsorbable organic fraction of
      around 1.2 mg/L DOC. The three oxidation methods employed, electrolytic oxidation
      over a boron-doped diamond electrode, UVA/TiO2 photocatalysis and sonolysis at 80
      kHz, showed similar behavior: during the first few minutes of treatment there was
      a moderate removal of DOC followed by further oxidation at a very slow rate.
      Electrolytic oxidation was capable of removing up to 36% at 17.8A after 30 min of
      treatment, sonolysis removed up to 34% at 135W after 60 min, while photocatalysis
      was capable of removing up to 50% at 60 min.

PMID- 18823927
TI  - Aerobic biodegradation of polyethylene glycols of different molecular weights in
      wastewater and seawater.
AB  - In order to distinguish between aerobic biodegradation of synthetic polymers in
      fresh and seawater, polyethylene glycols (PEGs) were systematically and
      comparatively investigated in inocula from municipal wastewater and seawater
      aquarium filters for the first time. The molecular weight (MW) of the PEGs,
      (HO(CH(2)CH(2)O)(n)H, n=3-1350) as representatives of water-soluble polymers,
      ranged from 250 to 57,800Da. The biodegradation was observed by removal of
      dissolved organic carbon and carbon dioxide production by applying standardized
      ISO and OECD test methods. Specific analyses using liquid chromatography mass
      spectrometry (LC-MS) and matrix-assisted laser desorption/ionization time-of
      flight mass spectrometry (MALDI-TOF-MS) were performed. All PEGs selected were
      completely biodegradable in freshwater media within 65d. PEGs with an MW up to
      14,600Da have a similar degradation pathway which is characterized by gradual
      splitting of C(2)-units off the chain resulting in formation of short-chain PEGs.
      In artificial seawater media, full biodegradation of PEGs up to 7400Da required
      more time than in freshwater. PEGs with MW 10,300 and 14,600Da were only
      partially degraded whereas PEGs with MW 26,600 and 57,800Da were not degraded for
      a period of 135d. The biodegradation pathway of PEG 250 and PEG 970 in seawater
      is similar to that for freshwater. For PEGs having an MW from 2000 to 10,300Da,
      the degradation pathway in seawater differs from the pathway of the shorter PEGs.

PMID- 18823928
TI  - The impact of sunlight on inactivation of indicator microorganisms both in river
      water and benthic biofilms.
AB  - A detailed knowledge on decay or inactivation kinetics of faecal indicator
      microorganism in rivers is essential for control of bathing water quality. Both
      reliable inactivation rate coefficients for such kinetics and the knowledge on
      pathogen accumulation in benthic biofilms are needed for the assessment of river
      self purification capability and for being able to make decisions for an
      optimized water management. Therefore, the inactivation kinetics for main
      indicator microorganisms like faecal coliforms and intestinal Enterococci in
      water and on stones of the river Isar (Germany) were measured at artificial
      sunlight radiation. A flume was built, containing Isar water and sediment. By
      adding a pulse of pre-treated sewage water, the subsequently change of indicator
      bacteria levels in the bulk and biofilm phase is measured. Bacterial inactivation
      was mainly dependent on sunlight intensity. Mean inactivation rate coefficients
      in the experimental set up with river water obtained for a radiation intensity
      comparable to average midday sunlight in June in 50 degrees north latitude
      (I((290-390nm))=40.0W/m(2)) were found to be 21.4d(-1) for faecal coliforms and
      20.0d(-1) for intestinal Enterococci. For a radiation intensity conform with the
      annual mean radiation in Germany (I((290-390nm))=8.0W/m(2)) inactivation rate
      coefficients were 12.7d(-1) for faecal coliforms and 9.3d(-1) for intestinal
      Enterococci. A measurement without direct artificial sunlight (I((290
      390nm))=0.08W/m(2)) yields inactivation rate coefficients of 3.4d(-1) for faecal
      coliforms and 1.7d(-1) for intestinal Enterococci, which were similar to those
      found in wastewater treatment ponds. Due to re-growth and better environmental
      conditions the concentrations of faecal coliforms and intestinal Enterococci
      within the biofilm were 10(2) to 10(4) fold higher compared to the bulk water
      depending on the exposure time.

PMID- 18823929
TI  - Trypanosoma cruzi congenital transmission in wild bats.
AB  - Trypanosoma cruzi congenital transmission in wild bats (Molossus molossus),
      associated with infected Rhodnius prolixus in a natural habitat from a rural
      locality in western Venezuela, is reported. T. cruzi blood circulating
      trypomastigotes in a pregnant bat were detected by parasitological methods.
      Polymerase chain reaction (PCR) assays carried out in samples from the heart and
      the fetus of the same infected female, revealed the presence of T. cruzi-specific
      DNA in both of the tissues, demonstrating transmission of the infection from the
      mother to the offspring. Eighty percent of the captured bats and 100% of the
      examined fetuses from pregnant specimens were shown to be infected by T. cruzi,
      indicating that M. molossus is a very susceptible species for this parasite, and
      that T. cruzi congenital transmission is a common phenomenon in nature. To our
      knowledge, this seems to be the first report on congenital T. cruzi transmission
      in wild bats in Venezuela. The circulation of T. cruzi lineage I in the study
      area was demonstrated by typing the isolates from bats and triatomine bugs
      captured in the same habitat. The potential epidemiological implication of these
      findings in areas where Chagas disease is endemic is discussed.

PMID- 18823930
TI  - Genetic diversity in the C-terminal 42 kDa region of merozoite surface protein-1
      of Plasmodium vivax (PvMSP-1(42)) among Indian isolates.
AB  - Plasmodium vivax merozoite surface protein 1 (PvMSP-1) is a leading malaria
      vaccine candidate. This protein is processed to give rise to various sized
      fragments during merozoite maturation. Here, we describe the analysis of genetic
      diversity in the 42 kDa C-terminal part of this protein among 33 Indian P. vivax
      isolates. A total of 27 haplotypes with 72 mutations and 0.0212+/-0.0005S.D. over
      all pi nucleotide diversity were observed among the isolates. Twenty-six of 27
      haplotypes reported here were new as they have not been reported so far from any
      other country. The difference between non-synonymous (dN) and synonymous (dS)
      mutations was found to be positive (0.0081+/-0.0051) for the entire 42 kDa
      region. Further analysis revealed that 33 kDa (MSP-1(33)) fragment of the MSP
      1(42) was highly polymorphic with pi nucleotide diversity 0.0290+/-0.0007S.D. The
      dN-dS for this region of MSP-1 was also positive (0.0114+/-0.0071S.E.). On the
      other hand, there was no non-synonymous mutation in the 19 kDa (MSP-1(19))
      fragment of the MSP-1(42) and thus it was highly conserved. In conclusion, MSP
      1(33) fragment was highly polymorphic and appeared to be under diversifying
      selection whereas there was no selection at MSP-1(19) region among the isolates.
      Present study will be helpful for the development of PvMSP-1 based vaccine
      against P. vivax malaria.

PMID- 18823931
TI  - Microbead device for isolating biotinylated oligonucleotides for use in mass
      spectrometric analysis.
AB  - We describe a prototypical device for isolating biotinylated oligonucleotides for
      use in mass spectrometric analysis. It consists of monomeric avidin-coated
      microbeads trapped in a pipette tip and has been used for genotyping single
      nucleotide polymorphisms (SNPs) with the previously developed solid phase capture
      single base extension (SPC-SBE) method. The device reduces processing time for
      genotyping by SPC-SBE and allows direct spotting of sample for rapid analysis by
      matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
      (MALDI-TOF MS). In addition, it allows simultaneous processing of multiple
      samples and can be reused after regeneration of beads with no carryover effects.
      These results indicate that the microbead device is a low-cost tool that enhances
      sample cleanup prior to MS for SNP genotyping.

PMID- 18823932
TI  - Atypical kinetic behavior of chloroperoxidase-mediated oxidative halogenation of
      polycyclic aromatic hydrocarbons.
AB  - We have identified an atypical kinetic behavior for the oxidative halogenation of
      several polycyclic aromatic hydrocarbons (PAHs) by chloroperoxidase (CPO) from
      Caldariomyces fumago. This behavior resembles the capacity of some members of the
      P450 family to simultaneously recognize several substrate molecules at their
      active sites. Indeed, fluorometric studies showed that PAHs exist in solution as
      monomers and pi-pi dimers that interact to different extents with CPO. The
      dissociation constants of dimerization were evaluated for every single PAH by
      spectrofluorometry. Furthermore, docking studies also suggest that CPO might
      recognize either one or two substrate molecules in its active site. The atypical
      sigmoidal kinetic behavior of CPO in the oxidative halogenation of PAHs is
      explained in terms of different kinetic models for non-heteroatomic PAHs
      (naphthalene, anthracene and pyrene). The results suggest that the actual
      substrate for CPO in this study was the pi-pi dimer for all evaluated PAHs.

PMID- 18823933
TI  - Human mevalonate diphosphate decarboxylase: characterization, investigation of
      the mevalonate diphosphate binding site, and crystal structure.
AB  - Expression in Escherichia coli of his-tagged human mevalonate diphosphate
      decarboxylase (hMDD) has expedited enzyme isolation, characterization, functional
      investigation of the mevalonate diphosphate binding site, and crystal structure
      determination (2.4A resolution). hMDD exhibits V(max)=6.1+/-0.5 U/mg; K(m) for
      ATP is 0.69+/-0.07 mM and K(m) for (R,S) mevalonate diphosphate is 28.9+/-3.3
      microM. Conserved polar residues predicted to be in the hMDD active site were
      mutated to test functional importance. R161Q exhibits a approximately 1000-fold
      diminution in specific activity, while binding the fluorescent substrate analog,
      TNP-ATP, comparably to wild-type enzyme. Diphosphoglycolyl proline (K(i)=2.3+/
      0.3 uM) and 6-fluoromevalonate 5-diphosphate (K(i)=62+/-5 nM) are competitive
      inhibitors with respect to mevalonate diphosphate. N17A exhibits a V(max)=0.25+/
      0.0 2U/mg and a 15-fold inflation in K(m) for mevalonate diphosphate. N17A's K(i)
      values for diphosphoglycolyl proline and fluoromevalonate diphosphate are
      inflated (>70-fold and 40-fold, respectively) in comparison with wild-type
      enzyme. hMDD structure indicates the proximity (2.8A) between R161 and N17, which
      are located in an interior pocket of the active site cleft. The data suggest the
      functional importance of R161 and N17 in the binding and orientation of
      mevalonate diphosphate.

PMID- 18823934
TI  - A solid-phase method for the extraction and measurement of anandamide from
      multiple human biomatrices.
AB  - N-Arachidonoylethanolamine (AEA, anandamide) was the first endocannabinoid to be
      identified and has since become associated with the mediation of several
      physiological functions and disease states. AEA has been isolated from numerous
      tissues and biofluids, in the low nanomolar range, using lipid extraction
      techniques with organic solvents. These techniques require the drying down of
      relatively large volumes of solvents, making them unsuitable for high-throughput
      analysis. Here we describe a solid-phase extraction (SPE) method for the
      investigation of AEA concentrations in human plasma, serum, milk, urine, amniotic
      fluid, peritoneal fluid, saliva, follicular fluid, and fluid from an ovarian
      cyst. AEA was detected in serum and plasma from blood isolated from 20 adult
      women (means+/-standard deviations: 0.68+/-0.29 and 0.64+/-0.28 nM,
      respectively), from pregnant women at term (1.37+/-0.42 nM), and from umbilical
      vein (1.26+/-0.33 nM) and umbilical artery (1.14+/-0.35nM), in milk (0.12+/-0.05
      nM) and from amniotic (0.03+/-0.02 nM), peritoneal (0.93+/-0.27 nM), follicular
      (1.17+/-0.51 nM), and ovarian cyst (0.32+/-0.01 nM) fluids. AEA was undetectable
      in saliva and urine. The 60% AEA extraction efficiency achieved with SPE from
      plasma was superior to the 19% efficiency achieved using the existing organic
      solvent extraction method. Limits of quantification and detection for AEA were
      also improved dramatically using SPE (8 and 4 fmol/ml) compared with organic
      extraction (25 and 18.75 fmol/ml plasma). These improvements allow the use of
      smaller plasma samples with SPE. Intra- and interday variability were comparable,
      and the mean AEA concentration of pooled plasma samples (1.18 nM, n=15) was
      identical with the two techniques. Similarly, when 56 plasma samples from
      laboring and nonlaboring women were analyzed using both techniques, no extraction
      method-dependent differences were observed. Consequently, we provide evidence for
      a robust SPE technique for the extraction of AEA from biomatrices to replace the
      existing liquid extraction methods, with the SPE technique being superior in
      terms of speed, extraction efficiency, and sample size required.

PMID- 18823935
TI  - The coupled chemomechanics of the F(1)-ATPase molecular motor.
AB  - The enzyme F(1)-ATPase is a rotary nanomotor in which the central gamma subunit
      rotates inside the cavity made of alpha(3)beta(3) subunits. The experiments
      showed that the rotation proceeds in steps of 120 degrees and each 120 degrees
      step consists of 80 degrees and 40 degrees substeps. Here the Author proposes a
      stochastic wave mechanics of the F(1)-ATPase motor and combines it with the
      structure-based kinetics of the F(1)-ATPase to form a chemomechanic coupled
      model. The model can reproduce quantitatively and explain the experimental
      observations about the F(1) motor. Using the model, several rate-limited
      situations about gamma subunit rotation are proposed, the effects of the friction
      and the load on the substeps are investigated and the chemomechanic coupled time
      during ATP hydrolysis cycle is determined.

PMID- 18823936
TI  - The role of respiration in the activation of photosynthesis upon illumination of
      dark adapted Chlamydomonas reinhardtii.
AB  - It is reported that O(2) is required for the activation of photosynthesis in dark
      adapted Chlamydomonas reinhardtii in State 1, under low light intensity. The
      concentration of dissolved O(2) of ca. 9 microM is sufficient to saturate the
      requirement. When the concentration of O(2) is 3 muM or below, the activation of
      photosynthesis is strongly inhibited by myxothiazol, a specific inhibitor of the
      mitochondrial cytochrome bc(1). The effect of this inhibitor decreases as the
      O(2) concentration is raised, to disappear completely above 50 muM. Low
      concentrations of uncouplers delay the activation of photosynthesis, but do not
      inhibit it when steady state is reached. It is concluded that in State 1 C.
      reinhardtii mitochondrial respiration is required for the activation of
      photosynthesis upon illumination of dark adapted cells only when the
      concentration of O(2) is too low (less than 5 muM) to allow an appreciable
      activity of the Mehler reaction. The role of respiration does not seem to be due
      to the synthesis of ATP by oxidative phosphorylation, because photosynthesis
      activation is not sensitive to oligomycin.

PMID- 18823937
TI  - The structure of urease activation complexes examined by flexibility analysis,
      mutagenesis, and small-angle X-ray scattering.
AB  - Conformational changes of Klebsiella aerogenes urease apoprotein (UreABC)(3)
      induced upon binding of the UreD and UreF accessory proteins were examined by a
      combination of flexibility analysis, mutagenesis, and small-angle X-ray
      scattering (SAXS). ProFlex analysis of urease provided evidence that the major
      domain of UreB can move in a hinge-like motion to account for prior chemical
      cross-linking results. Rigidification of the UreB hinge region, accomplished
      through a G11P mutation, reduced the extent of urease activation, in part by
      decreasing the nickel content of the mutant enzyme, and by sequestering a portion
      of the urease apoprotein in a novel activation complex that includes all of the
      accessory proteins. SAXS analyses of urease, (UreABC-UreD)(3), and (UreABC
      UreDF)(3) confirm that UreD and UreF bind near UreB at the periphery of the
      (UreAC)(3) structure. This study supports an activation model in which a domain
      shifted UreB conformation in (UreABC-UreDF)(3) allows CO(2) and nickel ions to
      gain access to the nascent active site.

PMID- 18823938
TI  - Ordering effects of cholesterol and its analogues.
AB  - Without any exaggeration, cholesterol is one of the most important lipid species
      in eukaryotic cells. Its effects on cellular membranes and functions range from
      purely mechanistic to complex metabolic ones, besides which it is also a
      precursor of the sex hormones (steroids) and several vitamins. In this review, we
      discuss the biophysical effects of cholesterol on the lipid bilayer, in
      particular the ordering and condensing effects, concentrating on the molecular
      level or inter-atomic interactions perspective, starting from two-component
      systems and proceeding to many-component ones e.g., modeling lipid rafts.
      Particular attention is paid to the roles of the methyl groups in the cholesterol
      ring system, and their possible biological function. Although our main research
      methodology is computer modeling, in this review we make extensive comparisons
      between experiments and different modeling approaches.

PMID- 18823939
TI  - Identification of candidate regulators of multipotency in human skeletal
      progenitor cells.
AB  - Stem cell differentiation is controlled intrinsically by dynamic networks of
      interacting lineage-specifying and multipotency genes. However, the relationship
      between internal genetic dynamics and extrinsic regulation of internal dynamics
      is complex and, in the case of skeletal progenitor cell differentiation,
      incompletely understood. In this study we elucidate a set of candidate markers of
      multipotency in human skeletal progenitor cells by systematic study of the
      relationships between gene expression and environmental stimulus. We used full
      genome cDNA microarrays to explore gene expression profiles in skeletal
      progenitor enriched populations derived from adult human bone marrow, minimally
      cultured in basal, osteogenic, chondrogenic, and adipogenic lineage-specifying
      culture conditions. We then used a variety of statistical clustering procedures
      to identify a small subset of genes which are related to these stromal lineages
      but are specific to none. For a selection of 11 key genes, conclusions of the
      microarray study were confirmed using quantitative real-time PCR.

PMID- 18823940
TI  - Altered microRNA expression patterns in irradiated hematopoietic tissues suggest
      a sex-specific protective mechanism.
AB  - To investigate involvement of miRNAs in radiation responses we used microRNAome
      profiling to analyze the sex-specific response of radiation sensitive
      hematopoietic lymphoid tissues. We show that radiation exposure resulted in a
      significant and sex-specific deregulation of microRNA expression in murine spleen
      and thymus tissues. Among the regulated miRNAs, we found that changes in
      expression of miR-34a and miR-7 may be involved in important protective
      mechanisms counteracting radiation cytotoxicity. We observed a significant
      increase in the expression of tumor-suppressor miR-34a, paralleled by a decrease
      in the expression of its target oncogenes NOTCH1, MYC, E2F3 and cyclin D1.
      Additionally, we show that miR-7 targets the lymphoid-specific helicase LSH, a
      pivotal regulator of DNA methylation and genome stability. While miR-7 was
      significantly down-regulated LSH was significantly up-regulated. These cellular
      changes may constitute an attempt to counteract radiation-induced
      hypomethylation. Tissue specificity of miRNA responses and possible regulation of
      miRNA expression upon irradiation are discussed.

PMID- 18823941
TI  - Efficient capture of infectious H5 avian influenza virus utilizing magnetic beads
      coated with anionic polymer.
AB  - The possible emergence of a pandemic influenza virus from the avian influenza
      virus (AIV) has become a serious threat. The isolation of viruses will be crucial
      for further virological analysis and the development of vaccines. However,
      currently, there is no simple method for facilitating the isolation of infectious
      AIV. Here, we have developed a simple method of capturing AIV using anionic
      magnetic beads. The method employed the capture of AIV (H5N1, H5N2, and H5N3)
      from liquid samples such as allantoic fluid (AF) and cell culture medium (CM)
      using magnetic beads coated with an anionic polymer, poly(methyl vinyl ether
      maleic anhydride). After their incubation with AIV-containing samples, the
      magnetic beads were separated from the supernatant by applying a magnetic field.
      The absorption of AIV on the beads was confirmed by immunochromatography and an
      enzyme-linked immunosorbent assay, which indicated the presence of hemagglutinin,
      neuraminidase, and nucleoprotein of AIV. Furthermore, the infectivity in chicken
      eggs of AIV captured by magnetic beads was similar to that of the starting
      materials. The capture of AIV using magnetic beads coated with anionic polymers
      will contribute to the sufficient recovery of infectious AIV and approach for
      potential pandemic influenza viruses.

PMID- 18823942
TI  - Role of integrin-linked kinase for functional capacity of endothelial progenitor
      cells in patients with stable coronary artery disease.
AB  - Number and function of endothelial progenitor cells (EPCs) are down-regulated in
      patients with coronary artery disease (CAD). Integrin-linked kinase (ILK) is a
      signal and adaptor protein that regulates survival of mature endothelial cells
      and vascular development. Here we show that EPC dysfunction in patients with CAD
      is paralleled by down-regulation of ILK while restoration of ILK expression
      rescues the migratory defect of CAD-EPCs. Human EPCs transduced with dominant
      negative ILK (DN-ILK) display significantly reduced expression of CD34(+)/VEGFR
      2(+), DiI-Ac-LDL uptake, and Ulex europaeus lectin binding. Mechanistically, DN
      ILK-transfected EPCs are characterized by decreased proliferation, while
      proliferation is increased in wild-type ILK-transfected EPCs. These effects are
      paralleled by changes in cyclin D1 expression, colony forming units, and
      cytoskeletal rearrangement. Functionally, ILK is necessary and sufficient for SDF
      1-triggered migration and adhesion in EPCs. These data extend current knowledge
      about the role of ILK in EPC biology and implicate ILK as a therapeutic target in
      CAD.

PMID- 18823943
TI  - Viral hijacking of human receptors through heterodimerization.
AB  - Epstein-Barr virus (EBV) is a human herpesvirus that primarily infects B
      lymphocytes and is associated with tumor development. Like other herpesviruses,
      EBV has pirated and modified host genes encoding important regulatory cellular
      proteins to take over cellular control after infection. One of these genes
      (BILF1) encodes a G protein-coupled receptor (GPCR). It is currently accepted
      that GPCRs exist and function as dimers. B lymphocyte migration and functioning
      is regulated by chemokines acting on their cognate receptors. In this study, we
      show that BILF1 heterodimerizes with various chemokine receptors using BRET,
      trFRET and co-immunoprecipitation. Importantly, heterodimerization of BILF1 with
      chemokine receptors may alter the responsiveness of B lymphocytes to chemokines
      thereby altering homing and homeostasis of infected B lymphocytes and might be
      essential for EBV dissemination and/or involved in EBV-induced pathogenesis.

PMID- 18823944
TI  - Inhibition of transcriptional activity of c-JUN by SIRT1.
AB  - c-JUN is a major component of heterodimer transcription factor AP-1 (Activator
      Protein-1) that activates gene transcription in cell proliferation, inflammation
      and stress responses. SIRT1 (Sirtuin 1) is a histone deacetylase that controls
      gene transcription through modification of chromatin structure. However, it is
      not clear if SIRT1 regulates c-JUN activity in the control of gene transcription.
      Here, we show that SIRT1 associated with c-JUN in co-immunoprecipitation of whole
      cell lysate, and inhibited the transcriptional activity of c-JUN in the mammalian
      two hybridization system. SIRT1 was found in the AP-1 response element in the
      matrix metalloproteinase-9 (MMP9) promoter DNA leading to inhibition of histone 3
      acetylation as shown in a ChIP assay. The SIRT1 signal was reduced by the AP-1
      activator PMA, and induced by the SIRT1 activator Resveratrol in the promoter
      DNA. SIRT1-mediaetd inhibition of AP-1 was demonstrated in the MMP9 gene
      expression at the gene promoter, mRNA and protein levels. In mouse embryonic
      fibroblast (MEF) with SIRT1 deficiency (SIRT1(-/-)), mRNA and protein of MMP9
      were increased in the basal condition, and the inhibitory activity of Resveratrol
      was significantly attenuated. Glucose-induced MMP9 expression was also inhibited
      by SIRT1 in response to Resveratrol. These data consistently suggest that SIRT1
      directly inhibits the transcriptional activity of AP-1 by targeting c-JUN.

PMID- 18823945
TI  - DNA-directed assembly of artificial multienzyme complexes.
AB  - This study aims to establish model systems for the exploration of proximity
      effects, occurring in natural multienzyme complexes. DNA-directed assembly of
      covalent conjugates of DNA oligonucleotides and Glucose Oxidase (GOX) or
      Horseradish peroxidase (HRP) was used to generate supramolecular complexes, in
      which the two enzymes were arranged with defined spatial orientation.
      Electrophoretic studies indicated that the assembly efficiency significantly
      depends on positional and sterical factors of the two DNA-enzyme conjugates.
      Kinetic rate measurements of the coupled reaction of glucose oxidation and Amplex
      Red peroxidation were carried out with microplate-immobilized DNA-GOX-HRP
      complexes, and the influence of Catalase on this reaction was determined. The
      kinetic measurements revealed a significant increase in the reactivity of the
      complexes, in which GOX and HRP were immobilized in direct proximity on a
      complementary DNA carrier.

PMID- 18823946
TI  - Helicobacter pylori neutrophil-activating protein promotes myeloperoxidase
      release from human neutrophils.
AB  - Helicobacter pylori infection induces acute and chronic inflammation and plays a
      key role in gastric mucosal diseases. H. pylori neutrophil-activating protein (HP
      NAP), one of its virulence factors, induces not only chemotactic but also
      oxidative burst responses of neutrophils. Activated neutrophils use
      myeloperoxidase (MPO) to generate many cytotoxic oxidants, which might result in
      gastric mucosal injury. In this study, we evaluated whether HP-NAP could promote
      MPO release from human neutrophils. Recombinant HP-NAP expressed in Escherichia
      coli was purified by two sequential gel filtration chromatographies and then
      subjected to syringe filtration for endotoxin removal. The purified recombinant
      HP-NAP assembles into a multimer with a secondary structure of the typical alpha
      helix. In addition to stimulating the production of reactive oxygen species, HP
      NAP is able to induce the secretion of MPO in human neutrophils. The increased
      MPO release from neutrophils induced by HP-NAP may be related to the pathogenesis
      of H. pylori-associated gastritis.

PMID- 18823947
TI  - Functional consequences of overexpressing the gap junction Cx43 in the
      cardiogenic potential of pluripotent human embryonic stem cells.
AB  - Gap junctions, encoded by the connexin (Cx) multi-gene family, couple adjacent
      cells and underlie cell-cell communications. Previous mouse studies suggest that
      Cxs play an important role in development but their role in human cardiogenesis
      is undefined. Human embryonic stem cells (hESC) provide a unique model for
      studying human differentiation. Lentivirus-mediated stable overexpression of Cx43
      in hESC (Cx43-hESC) did not affect colony morphology, karyotype and expression of
      pluripotency genes such as Oct4 but completely suppressed the formation of
      spontaneously beating, cardiomyocyte-containing clusters in embryoid bodies
      (EBs). Unlike control hEBs, the transcripts of several mesodermal markers
      (kallikrein, delta-globin, and CMP), ventricular myosin light chain and cardiac
      troponin I were absent or delayed. Transcriptomic and pathway analyses showed
      that 194 genes crucial for movement, growth, differentiation and maintenance were
      differentially expressed in Cx43-hESC. We conclude that Cx43 mediates the
      expression of an array of genes involved in human cardiogenesis, in addition to
      intercellular communication.

PMID- 18823948
TI  - RFamide neuropeptides inhibit murine and human adipose differentiation.
AB  - RFamide neuropeptides NPFF and NPAF affect gene expression in mature 3T3-L1
      adipocytes but their role on adipogenesis is unknown. Here, we show that NPFF,
      NPAF, and NPSF inhibited the differentiation of 3T3-F442A preadipocytes in a
      concentration-dependent manner, but had no effect on 3T3-L1 adipogenesis. All
      three neuropeptides also blocked the adipose differentiation of normal and lipoma
      derived human preadipocytes. The antiadipogenic effect of RFamide neuropeptides
      was linked with the overexpression of Id3 gene and the inhibition by NPAF
      remained after neuropeptide removal and further incubation of 3T3 cells with
      adipogenic medium. Our results show that NPFF, NPAF and NPSF negatively affect
      adipogenesis and suggest that these compounds participate in the regulation of
      the adipose tissue development by the central nervous system.

PMID- 18823949
TI  - Quantum dots for tracking cellular transport of lectin-functionalized
      nanoparticles.
AB  - Successful drug delivery by functionalized nanocarriers largely depends on their
      efficient intracellular transport which has not yet been fully understood. We
      developed a new tracking technique by encapsulating quantum dots into the core of
      wheat germ agglutinin-conjugated nanoparticles (WGA-NP) to track cellular
      transport of functionalized nanocarriers. The resulting nanoparticles showed no
      changes in particle size, zeta potential or biobinding activity, and the loaded
      probe presented excellent photostability and tracking ability. Taking advantage
      of these properties, cellular transport profiles of WGA-NP in Caco-2 cells was
      demonstrated. The cellular uptake begins with binding of WGA to its receptor at
      the cell surface. The subsequent endocytosis happened in a cytoskeleton-dependent
      manner and by means of clathrin and caveolae-mediated mechanisms. After endosome
      creating, transport occurs to both trans-Golgi and lysosome. Our study provides
      new evidences for quantum dots as a cellular tracking probe of nanocarriers and
      helps understand intracellular transport profile of lectin-functionalized
      nanoparticles.

PMID- 18823950
TI  - PCNA damage caused by antineoplastic drugs.
AB  - Structurally diverse chemotherapeutic and chemopreventive drugs, including
      camptothecin, doxorubicin, sanguinarine, and others, were found to cause covalent
      crosslinking of proliferating cell nuclear antigen (PCNA) trimers in mammalian
      cells exposed to fluorescent light. This PCNA damage was caused by both nuclear
      and cytoplasmically localizing drugs. For some drugs, the PCNA crosslinking was
      evident even with very brief exposures to laboratory room lighting. In the
      absence of drugs, there was no detectable covalent crosslinking of PCNA trimers.
      Other proteins were photo-crosslinked to PCNA at much lower levels, including
      crosslinking of additional PCNA to the PCNA trimer. The proteins photo
      crosslinked to PCNA did not vary with cell type or drug. PCNA was not crosslinked
      to itself or to other proteins by superoxide, hydrogen peroxide or hydroxyl
      radicals, but hydrogen peroxide caused monoubiquitination of PCNA. Quenching of
      PCNA photo-crosslinking by histidine, and enhancement by deuterium oxide, suggest
      a role for singlet oxygen in the crosslinking. SV40 large T antigen hexamers were
      also efficiently covalently photo-crosslinked by drugs and light. Photodynamic
      crosslinking of nuclear proteins by cytoplasmically localizing drugs, together
      with other evidence, argues that these drugs may reach the nucleoplasm in amounts
      sufficient to photodamage important chromosomal enzymes. The covalent
      crosslinking of PCNA trimers provides an extremely sensitive biomarker for
      photodynamic damage. The damage to PCNA and large T antigen raises the
      possibility that DNA damage signaling and repair mechanisms may be compromised
      when cells treated with antineoplastic drugs are exposed to visible light.

PMID- 18823951
TI  - A benzodiazepines derived compound, 4-(3-chlorophenyl)-1,3-dihydronaphtho [2,3
      b][1,4]diazepin-2-one (ND700C), inhibits fMLP-induced superoxide anion release by
      activating protein phosphatase 2A in human neutrophils.
AB  - We studied the mechanism underlying the inhibitory effect of a benzodiazepines
      derivative, 4-(3-chlorophenyl)-1,3-dihydronaphtho [2,3-b][1,4]diazepin-2-one
      (ND700C), on superoxide anion production induced by formly-methionyl-leucyl
      phenylalanine (fMLP) in human neutrophils. ND700C inhibited the fMLP-induced
      superoxide anion production and cathepsin G release in a concentration-dependent
      manner with respective IC50 values of 5.0+/-0.5 and 8.7+/-0.8muM. In addition,
      ND700C was found to suppress fMLP-induced intracellular calcium mobilization and
      the phosphorylation of ERK and Akt. In another study, ND700C was observed to
      cause a rapid increase in intracellular cAMP level by up to threefold.
      Furthermore, when H89 was used to inhibit cAMP-dependent protein kinase A (PKA),
      we discovered that ND700C's suppressive effects on calcium mobilization,
      phosphorylation, and superoxide anion production were abrogated. ND700C
      demonstrated additive effect on the PGE1-induced increase in cAMP. However, this
      additive effect was not demonstrated with the IBMX-induced rise in cAMP. Our
      results indicated that ND700C did not directly inhibit the activity of
      phosphodiesterase 4. In another set of experiments, calyculin A and okadaic acid
      (both protein phosphatase 2A inhibitors) were found to reverse ND700C's positive
      effect on cAMP level. This observation suggested the involvement of protein
      phosphatase 2A in ND700C's cAMP-elevating mechanism. We found that the activity
      of protein phosphatase 2A was activated by ND700C. Furthermore, protein
      phosphatase 2A was co-immunoprecipitated with phosphodiesterase 4 after ND700C
      treatment in human neutrophils. CONCLUSION: ND700C inhibited fMLP-induced
      superoxide anion production through a PKA-dependent pathway. ND700C increased
      cAMP by activating protein phosphatase 2A, which subsequently inhibited
      phosphodiesterase 4.

PMID- 18823952
TI  - Kinetic stabilization of microtubule dynamic instability by benomyl increases the
      nuclear transport of p53.
AB  - Using time-lapse confocal microscopy and enhanced green fluorescent protein
      tubulin transfected MCF-7 cells, we found that a tubulin-targeted antimitotic
      agent, benomyl at its half-maximal proliferation inhibitory concentration (5
      microM) strongly suppressed the rate and extent of growing and shortening
      excursions of individual microtubules in MCF-7 cells without noticeably
      depolymerizing the microtubule network or decreasing the polymerized mass of
      tubulin. Further, benomyl treatment caused an increase in the acetylation level
      of microtubules suggesting that it stabilizes microtubules. Under the conditions
      that suppressed the dynamic instability, a sharp increase in the nuclear
      accumulation of p53 in MCF-7 cells was observed in the presence of benomyl. Up
      regulation of bax and the increased nuclear accumulation of p21 upon benomyl
      treatment confirmed the activation of p53. Cisplatin caused an increase in the
      translocation of p53 into the nucleus in the presence of lower effective
      concentrations of benomyl while a decrease in the nuclear accumulation of p53 was
      observed in the presence of high concentrations of benomyl suggesting that the
      stabilized microtubules assist in the nuclear transportation of p53. Furthermore,
      increased localization of the light chain of the minus end directed motor protein
      dynein was detected on the microtubules in the benomyl-treated cells indicating
      that the suppression of microtubule dynamics may influence the binding of dynein
      on the microtubules and dynein-mediated cargo transport. Together the data
      indicate that benomyl inhibits mitosis primarily by suppressing the dynamic
      instability of microtubules and support the hypothesis that the kinetic
      stabilization of microtubules enhances the microtubule-mediated transport of p53
      into the nucleus.

PMID- 18823953
TI  - The neuronal activity of thalamic parafascicular nucleus is conversely regulated
      by nigrostriatal pathway and pedunculopontine nucleus in the rat.
AB  - The aim of the present study was to investigate changes in the firing activity of
      thalamic parafascicular nucleus (PF) neurons at different time periods after 6
      hydroxydopamine (6-OHDA) lesions of the substantia nigra pars compacta (SNc) and
      the role of the pedunculopontine nucleus (PPN) in these changes. In normal rats,
      the firing rate of PF neurons was 3.66+/-0.37 spikes/s. In rats with 6-OHDA
      lesions of the SNc, the firing rate of PF neurons slightly decreased to 3.19+/
      0.35 spikes/s during the third week compared to normal rats, unexpectedly, as
      moving on to fifth week, the firing rate increased significantly to 4.82+/-0.31
      spikes/s. In rats with ibotenic acid lesions of the PPN, the firing rate
      decreased significantly to 1.98+/-0.19 spikes/s compared to normal rats. When the
      SNc and PPN were double lesioned, the firing rate of PF neurons decreased
      significantly to 2.36+/-0.23 spikes/s during the third week and 2.16+/-0.16
      spikes/s during the fifth week post-lesions. The separate lesions of the PPN,
      SNc, and double lesion of both in the rats did not change the firing pattern of
      PF neurons compared to normal rats. These findings demonstrate that PF neurons
      are hyperactive in the 6-OHDA-lesioned rats suggesting the implication of this
      nucleus in the pathophysiology of parkinsonism. Furthermore, the fact that the
      PPN lesions induced a decrease in the firing rate of PF neurons in normal and SNc
      lesioned rats suggests that the PF is under major control of the PPN.

PMID- 18823954
TI  - Organization of food protection behavior is differentially influenced by 192 IgG
      saporin lesions of either the medial septum or the nucleus basalis
      magnocellularis.
AB  - Converging lines of evidence have supported a role for the nucleus basalis
      magnocellularis (NB) in attentional mechanisms; however, debate continues
      regarding the role of the medial septum in behavior (MS). Recent studies have
      supported a role for the septohippocampal system in the online processing of
      internally generated cues. The current study was designed to investigate a
      possible double dissociation in rat food protection behavior, a natural behavior
      that has been shown to depend on external and internal sources of information.
      The study examined the effects of intraparenchymal injections of 192 IgG-saporin
      into either the MS or NB on the organization of food protection behavior. NB
      cholinergic lesions reduced the number of successful food protection behaviors
      while sparing the temporal organization of food protection behavior. In contrast,
      MS cholinergic lesions disrupted the temporal organization of food protection
      behavior while sparing the ability to successfully protect food items. These
      observations are consistent with a double dissociation of NB and MS cholinergic
      systems' contributions to processing external and internal sources of information
      and provide further evidence for the septohippocampal system's involvement in
      processing internally generated cues.

PMID- 18823956
TI  - Fos expression induced by milk ingestion in the caudal brainstem of neonatal
      rats.
AB  - Prominent Fos expression in the nucleus of the solitary tract (NTS) related to
      feeding has been reported in the brainstem of adult animals. In this study, we
      used a Fos-guided immunohistochemical approach to determine the brainstem areas
      activated specifically in response to milk ingestion in rat pups at two different
      ages. Rats at 9 or 18 days postpartum were isolated from the mother for a 6-h
      period, after which they were returned to the mother for a suckling period of
      either 5 or 90 min and then perfused at 90 min after the beginning of suckling.
      Control groups were sacrificed before or after the 6-h-deprivation period and
      showed little or no Fos-ir. In contrast, a 90-min-suckling episode after 6 h of
      deprivation induced strong Fos-ir in the caudal regions of the NTS and in the
      spinal nucleus of the trigeminal (SPV). Moderate expression was observed in the
      rostral NTS and in the nucleus raphe obscurus. In rat pups that suckled for only
      5 min, the main area activated was the SPV. Fos immunostaining was detected in
      only 1% of the catecholaminergic neurons from the NTS after milk ingestion. The
      experimental design employed here allowed us to distinguish brainstem areas
      activated by milk ingestion from those activated by suckling action in rat pups.
      In contrast to adult rats, catecholaminergic neurons from the caudal NTS seem to
      contribute little to the regulation of feeding at this age.

PMID- 18823955
TI  - Pregnant rats show enhanced spatial memory, decreased anxiety, and altered levels
      of monoaminergic neurotransmitters.
AB  - Spatial memory, anxiety and central monoaminergic activities were measured in non
      pregnant (NP) and pregnant females during two time periods of pregnancy:
      gestational days 7-9 (GD7, GD9) and gestation days 16-18 (GD16, GD18). Pregnant
      females discriminated between object locations on both test days on an object
      placement task, whereas NP females were unable to discriminate between locations.
      Pregnant females displayed decreased anxiety on the elevated plus maze on GD9
      compared to NP females, followed by increased anxiety-like behavior on the
      elevated plus maze on GD18. Monoamine levels and activity (as indexed by turnover
      ratio) were measured in prefrontal cortex (PFC), CA1 and CA3 regions of the
      hippocampus (areas important for memory), and medial preoptic area (mPOA, an area
      important in display of maternal behaviors). In the PFC, NP females generally had
      higher monoamine levels and turnover ratios; however, norepinephrine (NE)
      turnover was higher in pregnant females at GD18. In the CA1 and CA3 regions of
      the hippocampus, monoamine levels and turnover ratios were generally higher
      during pregnancy, particularly on GD9. In the mPOA, pregnancy was associated with
      increases in NE activity, a previously unreported finding. The present study
      expands upon existing research indicating that pregnancy is beneficial to spatial
      memory and may decrease anxiety. Changes in monoamine levels and activity in
      specific brain regions indicate that the dopamine, norepinephrine and serotonin
      systems may contribute to the observed behavioral differences.

PMID- 18823957
TI  - Transient up-regulation of cocaine- and amphetamine-regulated transcript peptide
      (CART) immunoreactivity following ethanol withdrawal in rat hypothalamus.
AB  - We investigated the profile of CART immunoreactivity in some discrete
      hypothalamic nuclei following chronic ethanol treatment and withdrawal
      conditions. Adult, male, Sprague-Dawley rats were fed with liquid diet (pair-fed)
      or liquid diet containing ethanol (ethanol-fed) for 15 days. Thereafter, all the
      animals were given access to ethanol free nutritionally balanced liquid diet and
      killed at 0, 24, 48 and 72 h post-withdrawal, and their brains processed for
      immunocytochemistry using monoclonal antibodies against CART. CART-immunoreactive
      fibers, but not the cells, were significantly increased in the paraventricular
      nucleus (PVN). However, the profile of CART-immunoreactive cells and/or fibers in
      the periventricular area (PeA), arcuate nucleus (ARC), perifornical area
      inclusive of lateral hypothalamus (LH) and tuber cinereum (TC), dorsomedial
      (DMH), and ventromedial (VMH) hypothalamus at the 0 h ethanol withdrawal time
      point was quite similar to that in the pair-fed control rats. Twenty-four hours
      following ethanol withdrawal, the immunoreactivity in all these areas was
      dramatically increased. While significant reduction in CART immunoreactivity was
      noticed in the PVN, PeA, ARC and VMH at 48 h, immunoreactive profile was restored
      to normal by 72 h post-ethanol withdrawal. The immunoreactive profile in the LH,
      TC and DMH resembled that of the pair-fed groups at 48 and 72 h post-withdrawal
      intervals. However, CART-immunoreactive profile in the supraoptic nucleus did not
      respond to the chronic ethanol treatment and/or withdrawal. We suggest that
      transient up-regulation of CART in some discrete hypothalamic nuclei following
      ethanol withdrawal, at least in part, may contribute to the pathogenesis of
      ethanol withdrawal-induced symptoms like anxiety and anorexia.

PMID- 18823958
TI  - A novel neuroprotective role of a small peptide from flesh fly, 5-S-GAD in the
      rat retina in vivo.
AB  - N-beta-Alanyl-5-S-glutathionyl-3,4-dihydroxyphenylalanine (5-S-GAD), an
      antibacterial substance isolated from flesh fly, has been described as having
      multipotential biological activities toward various tissues. However, there has
      been no report testing its action on neural cells. In the present study, we
      investigate whether 5-S-GAD is neurotoxic or neuroprotective to the rat retina. 5
      S-GAD at high doses (more than 200 pmol) induced apoptosis of retinal neurons 7
      days after intraocular injection. 5-S-GAD at low doses (2-20 pmol) significantly
      attenuated the loss of retinal ganglion cells (RGCs) and the thinning of inner
      retina induced by NMDA in a dose-dependent manner. To understand the protective
      mechanism of 5-S-GAD, we investigated the influence of 5-S-GAD on the cell
      survival molecules, phospho-Akt and Bcl-2. 5-S-GAD (2-20 pmol) rapidly increased
      phospho-Akt expression 1-7 days and Bcl-2 expression 3-7 days after injection.
      The cellular localization of this increase was both in bipolar cells and RGCs.
      This neurosurvival effect of 5-S-GAD was further tested using another model of
      optic nerve injury. 5-S-GAD significantly blocked the apoptosis of RGCs 7 days
      after optic nerve crush. These results show that 5-S-GAD (2-20 pmol) protects
      against the NMDA- and optic nerve crush-induced apoptosis of RGCs. The
      neuroprotective action of 5-S-GAD in the retina might be mediated by the cell
      survival phospho-Akt/Bcl-2 system and offers a therapeutic option to rescue RGCs
      from various types of excitotoxic disease, such as glaucoma.

PMID- 18823959
TI  - Endocannabinoids mediate neuroprotection after transient focal cerebral ischemia.
AB  - The endocannabinoids anandamide (AEA) and palmitoylethanolamide (PEA) act as
      endogenous protective factors of the brain, using different pathways of
      neuroprotection against neuronal damage. Although several in vivo and in vitro
      studies confirmed the neuroprotective efficacy of endocannabinoids, no
      experimental settings compare and explore the neuroprotective potential of AEA
      and PEA in an acute stroke model. In this study, we investigated the
      neuroprotective potential by infarct measurement after high (30 mg/kg body
      weight) and low dosage administration (10 mg/kg body weight) of the
      endocannabinoid PEA in 49 male Wistar rats. In additions we studied infarct
      volumes of 22 male Wistar rats receiving the endocannabinoid AEA with a dosage of
      10 mg/kg body weight or placebo. The neurological outcome was assessed 24 h after
      ischemia. Endocannabinoids were given intraperitoneally 30 min after initiation
      of transient middle cerebral artery occlusion (tMCAO). Infarct volume was
      calculated on the basis of 2.3.5-triphenyltetrazolium chloride staining. In the
      PEA high-dose group a significant total infarct reduction of 35% compared to the
      control group could be observed. AEA-treated rats presented a total infarct
      reducing effect of 26% compared to controls. Neurological scores, evaluated 24 h
      after tMCAO and physiological parameters, obtained 45 and 90 min after onset of
      ischemia showed no significant differences among the groups. As shown here, the
      endocannabinoids AEA and PEA achieved a significant neuroprotective effect by
      reducing size of infarcted tissue after tMCAO. Both endocannabinoids may have the
      potential to treat acute stroke and exert neuroprotection through a variety of
      mechanisms.

PMID- 18823960
TI  - Increased exploratory activity of APP23 mice in a novel environment is reversed
      by siRNA.
AB  - Genetic abnormalities in amyloid precursor protein (APP) are associated with
      Down's syndrome and familial Alzheimer's disease where hallmark plaques contain A
      beta peptides derived from APP. Both APP and its derivatives are implicated in
      neurodegenerative processes and may play important physiological and
      pathophysiological roles in synaptic function. Here, we show that young APP23
      transgenic mice overexpressing human APP with the Swedish double mutation display
      altered novelty seeking behavior before the age of plaque onset. Using short
      interfering RNA (siRNA) targeted against APP, we investigate the direct
      contribution of APP and its derivatives to this behavioral deficit. After
      validating siRNAs targeting human APP in vitro, siRNAs were infused directly into
      the brain of APP23 mice for 2 weeks. Behavioral analysis shows that infusion of
      siRNA targeted against APP completely reverses increased exploratory activity in
      APP23 mice. Collectively, these data suggest that excessive APP and/or its
      derivatives, causes a hyperactive phenotype in APP23 mice when placed in a novel
      environment, which is fully reversible and not linked to plaque deposits.

PMID- 18823961
TI  - Differential effects of glutamate transporter inhibitors on the global
      electrophysiological response of astrocytes to neuronal stimulation.
AB  - Astrocytes are responsible for regulating extracellular levels of glutamate and
      potassium during neuronal activity. Glutamate clearance is handled by glutamate
      transporter subtypes glutamate transporter 1 and glutamate-aspartate transporter
      in astrocytes. DL-threo-beta-benzyloxyaspartate (TBOA) and dihydrokainate (DHK)
      are extensively used as inhibitors of glial glutamate transport activity. Using
      whole-cell recordings, we characterized the effects of both transporter
      inhibitors on afferent-evoked astrocyte currents in acute cortical slices of 3
      week-old rats. When neuronal afferents were stimulated, passive astrocytes
      responded by a rapid inward current followed by a persistent tail current. The
      first current corresponded to a glutamate transporter current. This current was
      inhibited by both inhibitors and by tetrodotoxin. The tail current is an inward
      potassium current as it was blocked by barium. Besides inhibiting transporter
      currents, TBOA strongly enhanced the tail current. This effect was barium
      sensitive and might be due to a rise in extracellular potassium level and
      increased glial potassium uptake. Unlike TBOA, DHK did not enhance the tail
      current but rather inhibited it. This result suggests that, in addition to
      inhibiting glutamate transport, DHK prevents astrocyte potassium uptake, possibly
      by blockade of inward-rectifier channels. This study revealed that, in brain
      slices, glutamate transporter inhibitors exert complex effects that cannot be
      attributed solely to glutamate transport inhibition.

PMID- 18823962
TI  - Filling and mining the reactive metabolite target protein database.
AB  - The post-translational modification of proteins is a well-known endogenous
      mechanism for regulating protein function and activity. Cellular proteins are
      also susceptible to post-translational modification by xenobiotic agents that
      possess, or whose metabolites possess, significant electrophilic character. Such
      non-physiological modifications to endogenous proteins are sometimes benign, but
      in other cases they are strongly associated with, and are presumed to cause,
      lethal cytotoxic consequences via necrosis and/or apoptosis. The Reactive
      Metabolite Target Protein Database (TPDB) is a searchable, freely web-accessible
      (http://tpdb.medchem.ku.edu:8080/protein_database/) resource that attempts to
      provide a comprehensive, up-to-date listing of known reactive metabolite target
      proteins. In this report we characterize the TPDB by reviewing briefly how the
      information it contains came to be known. We also compare its information to that
      provided by other types of "-omics" studies relevant to toxicology, and we
      illustrate how bioinformatic analysis of target proteins may help to elucidate
      mechanisms of cytotoxic responses to reactive metabolites.

PMID- 18823963
TI  - Hypolipidimic and antioxidant activities of oleuropein and its hydrolysis
      derivative-rich extracts from Chemlali olive leaves.
AB  - Oleuropein-rich extracts from olive leaves and their enzymatic and acid
      hydrolysates, respectively rich in oleuropein aglycone and hydroxytyrosol, were
      prepared under optimal conditions. The antioxidant activities of these extracts
      were examined by a series of models in vitro. In this study the lipid-lowering
      and the antioxidative activities of oleuropein, oleuropein aglycone and
      hydroxytyrosol-rich extracts in rats fed a cholesterol-rich diet were tested.
      Wistar rats fed a standard laboratory diet or cholesterol-rich diets for 16 weeks
      were used. The serum lipid levels, the thiobarbituric acid reactive substances
      (TBARS) level, as indicator of lipid peroxidation, and the activities of liver
      antioxidant enzymes (superoxide dismutase (SOD) and catalase (CAT)) were
      examined. The cholesterol-rich diet induced hyperlipidemia resulting in the
      elevation of total cholesterol (TC), triglycerides (TG) and low-density
      lipoprotein cholesterol (LDL-C). Administration of polyphenol-rich olive leaf
      extracts significantly lowered the serum levels of TC, TG and LDL-C and increased
      the serum level of high-density lipoprotein cholesterol (HDL-C). Furthermore, the
      content of TBARS in liver, heart, kidneys and aorta decreased significantly after
      oral administration of polyphenol-rich olive leaf extracts compared with those of
      rats fed a cholesterol-rich diet. In addition, these extracts increased the serum
      antioxidant potential and the hepatic CAT and SOD activities. These results
      suggested that the hypocholesterolemic effect of oleuropein, oleuropein aglycone
      and hydroxytyrosol-rich extracts might be due to their abilities to lower serum
      TC, TG and LDL-C levels as well as slowing the lipid peroxidation process and
      enhancing antioxidant enzyme activity.

PMID- 18823964
TI  - Tetrahydroindenoindole inhibits the progression of diabetes in mice.
AB  - Diabetes is characterized by elevated fasting blood glucose (FBG) resulting from
      improper insulin regulation and/or insulin resistance. Herein we used female
      C57BL/6J mouse models for type 1 diabetes (streptozotocin [STZ] treatment) and
      type 2 diabetes (high-fat diet) to examine the ability of 4b,5,9b,10
      tetrahydroindeno[1,2-b]indole (THII) to intervene in the progression of diabetes.
      THII (100 microM in drinking water) significantly diminished and partially
      reversed the increase in FBG levels produced by STZ. After 10 weeks on a high-fat
      diet, mice had normal FBG levels, but exhibited fasting hyperinsulemia and loss
      of glucose tolerance. THII significantly diminished these changes in glucose and
      insulin. In isolated liver mitochondria, THII inhibited succinate-dependent
      H(2)O(2) production, while in white adipose tissue, THII inhibited NADPH oxidase
      mediated H(2)O(2) production and lipid peroxidation. Without intervention, such
      oxidative processes might otherwise promote diabetogenesis via inflammatory
      pathways. THII also increased O(2) consumption and lowered respiratory quotient
      (CO(2) produced/O(2) consumed) in vivo, indicating a greater utilization of fat
      for metabolic fuel. Increased metabolic utilization of fat correlated with a
      decrease in the rate of body weight gain in THII-treated mice fed the high-fat
      diet. We conclude that THII may retard the progression of diabetes via multiple
      pathways, including the inhibition of oxidative and inflammatory pathways.

PMID- 18823965
TI  - Modulation of rat pulmonary carcinogen-metabolising enzyme systems by the
      isothiocyanates erucin and sulforaphane.
AB  - The objective of this study was to evaluate the potential of the structurally
      related aliphatic isothiocyanates erucin and sulforaphane to modulate the
      pulmonary carcinogen-metabolising enzyme systems in rat lung, a target organ of
      their chemopreventive activity. Precision-cut rat lung slices were prepared and
      incubated for 24 h with a range of concentrations of either erucin or
      sulforaphane, up to 50microM. Neither compound modulated the O-deethylation of
      ethoxyresorufin whereas they elevated markedly CYP1A1 and, to a lesser extent,
      CYP1B1 apoprotein levels. Neither compound influenced the O-depentylation of
      pentoxyresorufin or CYP2B apoprotein levels, but sulforaphane caused a modest
      increase in CYP3A2 apoprotein levels. Pulmonary quinone reductase activity,
      monitored using 3-(4,5-dimethylthiazo-2-yl)-2,5-diphenyltetrazolium bromide as
      substrate, was markedly up-regulated by both compounds and was paralleled by a
      similar rise in protein levels. Both compounds increased cytosolic glutathione S
      transferase activity, measured using 1-chloro-2,4-dinitrobenzene as the accepting
      substrate; a modest rise was seen in GSTalpha protein levels, determined
      immunologically, whereas GSTpi levels were un-affected by the same treatment.
      Finally, both erucin and sulforaphane increased total glutathione concentration
      in lung cytosol. It is concluded that these aliphatic isothiocyanates have the
      potential to antagonise the carcinogenicity of pulmonary carcinogens by
      stimulating the in situ detoxication of their DNA-binding genotoxic metabolites.

PMID- 18823966
TI  - Relationships between gene polymorphisms of folate-related proteins and vitamins
      and metabolites in pregnant women and neonates.
AB  - BACKGROUND: The methylenetetrahydrofolate reductase (MTHFR), glutamate
      carboxypeptidase II (GCPII) and reduced folate carrier (RFC1) gene polymorphisms
      were associated with folate status. We investigated the effects of these
      polymorphisms on serum folate (SF) and folate-related metabolites in mothers and
      their neonates. METHODS: Cobalamin (Cbl), SF, total homocysteine (tHcy),
      methylmalonic acid (MMA), S-adenosylmethionine (SAM), and S-adenosylhomocysteine
      (SAH) were measured in 275 healthy women and their neonates. MTHFR C677T, GCPII
      C1561T and RFC1 A80G polymorphisms were determined by PCR-RFLP. RESULTS: Maternal
      tHcy was affected individually by MTHFR C677T and GCPII C1561T polymorphisms and
      by combined genotypes MTHFR 677TT/GCPII 1561CC and MTHFR 677TT/RFC1 80AG. The
      MTHFR and RFC1 polymorphisms were not associated with variations in vitamins or
      SAM, SAH and MMA in neonates. Neonatal tHcy was predicted directly by maternal
      tHcy and inversely by maternal SF, neonatal Cbl and neonatal RFC1 80G allele
      (AG+GG genotypes). Maternal MMA and SAM/SAH were predicted by creatinine and Cbl,
      respectively. Neonatal MMA was predicted by maternal MMA and GCPII 1561T allele
      (CT+TT genotypes) and by neonatal Cbl. CONCLUSIONS: Maternal tHcy was affected by
      MTHFR C677T, RFC1 A80G and GCPII C1561T polymorphisms. Maternal GCPII C1561T
      variant was associated with neonatal MMA. Neonatal RFC1 A80G polymorphism
      influenced tHcy in neonates.

PMID- 18823967
TI  - Performance characteristics of the Access pregnancy-associated plasma protein-A
      assay.

PMID- 18823968
TI  - Brain natriuretic peptide correlates with the extent of atrial fibrillation
      associated silent brain lesions.
AB  - OBJECTIVE: Identification of plasma markers indicative for atrial fibrillation
      associated silent brain lesions. DESIGN AND METHODS: 1. Comparative determination
      of the plasma concentrations of secretagogin, S100B, neuropeptide Y, brain fatty
      acid binding protein, matrix metalloprotease 9, brain natriuretic peptide, and of
      D-Dimer in 222 patients with atrial fibrillation and 28 controls by immunoassays.
      2. Correlation of the biochemical marker plasma concentration with the extent of
      silent white matter brain lesions, as determined by the Fazekas score and N
      acetylaspartate-spectroscopy. RESULTS: 1. Plasma concentrations of brain
      natriuretic peptide, of neuropeptide Y, and of matrix metalloprotease 9 were
      significantly higher (all with a p<0.05) in patients suffering from atrial
      fibrillation than in control subjects. 2. Brain natriuretic peptide correlated
      significantly with the Fazekas score (R=0.41; p<0.005). 3. Brain natriuretic
      peptide plasma concentrations were significantly higher in patients with a
      pathological N-acetylaspartate magnetic resonance-spectrometry (p<0.05).
      CONCLUSION: Brain natriuretic peptide plasma concentrations correlate with the
      extent of atrial fibrillation-associated silent brain lesions.

PMID- 18823969
TI  - Internalization of plasma membrane Ca2+-ATPase during Xenopus oocyte maturation.
AB  - A transient increase in intracellular Ca(2+) is the universal signal for egg
      activation at fertilization. Eggs acquire the ability to mount the specialized
      fertilization-specific Ca(2+) signal during oocyte maturation. The first Ca(2+)
      transient following sperm entry in vertebrate eggs has a slow rising phase
      followed by a sustained plateau. The molecular determinants of the sustained
      plateau are poorly understood. We have recently shown that a critical determinant
      of Ca(2+) signaling differentiation during oocyte maturation is internalization
      of the plasma membrane calcium ATPase (PMCA). PMCA internalization is
      representative of endocytosis of several integral membrane proteins during oocyte
      maturation, a requisite process for early embryogenesis. Here we investigate the
      mechanisms regulating PMCA internalization. To track PMCA trafficking in live
      cells we cloned a full-length cDNA of Xenopus PMCA1, and show that GFP-tagged
      PMCA traffics in a similar fashion to endogenous PMCA. Functional data show that
      MPF activation during oocyte maturation is required for full PMCA
      internalization. Pharmacological and co-localization studies argue that PMCA is
      internalized through a lipid raft endocytic pathway. Deletion analysis reveal a
      requirement for the N-terminal cytoplasmic domain for efficient internalization.
      Together these studies define the mechanistic requirements for PMCA
      internalization during oocyte maturation.

PMID- 18823970
TI  - Establishment of testis-specific SOX9 activation requires high-glucose metabolism
      in mouse sex differentiation.
AB  - In mouse sex differentiation, SRY promotes Sertoli cell differentiation via SOX9
      action, resulting in testis formation. SRY/SOX9 also initiates various testis
      specific morphogenic events including glycogenesis in pre-Sertoli cells,
      suggesting the importance of glucose storage for certain SRY/SOX9-downstream
      events in gonadal sex determination. However, it remains unclear which cell types
      and what molecular/cellular events require sex-dimorphic high-energy metabolic
      rate. Here we show that the establishment of SOX9 activation itself is a
      metabolically active process with sex-dimorphic high-energy requirements in
      gonadal sex differentiation. The glucose-deprivation and metabolic rescue
      experiments using genital ridge cultures of the XY/XX-wildtype and XX/Sry
      transgenic embryos demonstrated that, among the various somatic cell types, pre
      Sertoli cells are the most sensitive to glucose starvation despite the
      differences between XX/Sry and XY genotypes. Moreover, our data showed that, in
      developing pre-Sertoli cells, the high-glucose metabolic state is required for
      the establishment of SOX9 expression through an ECM (extracellular matrix)
      mediated feed-forward pathway. In contrast, the expression of SRY, SF1/Ad4Bp,
      GATA4 and WT1, as well as initiation of early SOX9 expression, is properly
      maintained in the glucose-deprived condition. Therefore, our results imply the
      metabolic importance of the high-glucose condition for the establishment of SOX9
      activation in testis differentiation.

PMID- 18823971
TI  - GDF3 is a BMP inhibitor that can activate Nodal signaling only at very high
      doses.
AB  - Within the TGF-beta superfamily, there are approximately forty ligands divided
      into two major branches: the TGF-beta/Activin/Nodal ligands and the BMP/GDF
      ligands. We studied the ligand GDF3 and found that it inhibits signaling by its
      co-family members, the BMPs; however, GDF3 has been described by others to have
      Nodal-like activity. Here, we show that GDF3 can activate Nodal signaling, but
      only at very high doses and only upon mRNA over-expression. In contrast, GDF3
      inhibits BMP signaling upon over-expression of GDF3 mRNA, as recombinant protein,
      and regardless of its dose. We therefore further characterized the mechanism
      through which GDF3 protein acts as a specific BMP inhibitor and found that the
      BMP inhibitory activity of GDF3 resides redundantly in the unprocessed,
      predominant form and in the mature form of the protein. These results confirm and
      extend the activity that we described for GDF3 and illuminate the experimental
      basis for the different observations of others. We suggest that GDF3 is either a
      bi-functional TGF-beta ligand, or, more likely, that it is a BMP inhibitor that
      can artificially activate Nodal signaling under non-physiological conditions.

PMID- 18823972
TI  - Inhibition of BMPs by follistatin is required for FGF3 expression and segmental
      patterning of the hindbrain.
AB  - A network of molecular interactions is required in the developing vertebrate
      hindbrain for the formation and anterior-posterior patterning of the rhombomeres.
      FGF signaling is required in this network to upregulate the expression of the
      Krox20 and Kreisler segmentation genes, but little is known of how FGF gene
      expression is regulated in the hindbrain. We show that the dynamic expression of
      FGF3 in chick hindbrain segments and boundaries is similar to that of the BMP
      antagonist, follistatin. Consistent with a regulatory relationship between BMP
      signaling and FGF3 expression, we find that an increase in BMP activity due to
      blocking of follistatin translation by morpholino antisense oligonucleotides or
      overexpression of BMP results in strong inhibition of FGF3 expression.
      Conversely, addition of follistatin leads to an increase in the level of FGF3
      expression. Furthermore, the segmental inhibition of BMP activity by follistatin
      is required for the expression of Krox20, Hoxb1 and EphA4 in the hindbrain. In
      addition, we show that the maintenance of FGF3 gene expression requires FGF
      activity, suggestive of an autoregulatory loop. These results reveal an
      antagonistic relationship between BMP activity and FGF3 expression that is
      required for correct segmental gene expression in the chick hindbrain, in which
      follistatin enables FGF3 expression by inhibiting BMP activity.

PMID- 18823973
TI  - The nebulette repeat domain is necessary for proper maintenance of tropomyosin
      with the cardiac sarcomere.
AB  - Nebulette is a cardiac-specific isoform of the giant actin-binding protein
      nebulin. Nebulette, having a mass of approximately 100 kDa, is only predicted to
      extend 150 nm from the edge of the Z-lines. Overexpression of the nebulette C
      terminal linker and/or SH3 domains in chicken cardiomyocytes results in a loss of
      endogenous nebulette with a concomitant loss of tropomyosin (TPM) and troponin,
      as well as a shortening of the thin filaments. These data suggest that
      nebulette's position in the sarcomere is important for the maintenance of TPM,
      troponin and thin filament length. To evaluate this hypothesis, N-terminal nested
      truncations tagged with GFP were expressed in chicken cardiomyocytes and the
      cells were analyzed for the distribution of myofilament proteins. Minimal effects
      on the myofilaments were observed with N-terminal deletions of up to 10 modules;
      however, deletion of 15 modules replicated the phenotype observed with expression
      of the C-terminal fragments. Expression of internal deletions of nebulette
      verifies that a site between module 10 and 15 is important for TPM maintenance
      within the sarcomeric lattice. We have additionally isolated TPM cDNAs from a
      yeast two hybrid (Y2H) analysis. These data indicate the importance of the
      nebulette-TPM interactions in the maintenance and stability of the thin
      filaments.

PMID- 18823974
TI  - Rebamipide affects the efficiency of colchicine for the herpes simplex virus
      induced inflammation in a Behcet's disease mouse model.
AB  - Rebamipide inhibits free radicals derived from activated neutrophils and
      decreases the inhibiting inflammatory cytokine. Behcet's disease (BD) is a
      chronic, multi-systemic inflammatory disorder with arthritic, gastrointestinal,
      mucocutaneous, ocular, vascular, and central nervous system involvement. This
      disease has a chronic course with periodic exacerbations and progressive
      deterioration. To study the effect of rebamipide treatment to BD-like mice,
      combination treatment with rebamipide and colchicine was compared to colchicine
      treatment. Colchicine is one of the most frequently prescribed medicine to the
      patients with BD. For each BD mouse, 200 microl gastric fluid or 2 microg
      colchicine or 150 microg rebamipide or 2 microg colchicine plus 150 microg
      rebamipide was treated orally once per day. Treatment was done for 5 consecutive
      days. Two hour or 20 days after last administration, spleens were isolated for RT
      PCR and real time PCR, and serum was collected for ELISA. In the combination
      treated group, TNF alpha, MIP-1 alpha, p22 phox, p47 phox, and gp91 phox mRNA
      expressions were lower than rebamipide treated or colchicine treated groups by
      reverse transcriptase PCR. NADPH oxidase subunits mRNA were markedly
      downregulated compared to the colchicine treated group by real time PCR. At 20
      days after administration, combination treatment decreased 23.5% of the severity
      score compared to before administration. In contrast, colchicine treatment
      decreased 14.3% of the severity score compared to before administration.
      Rebamipide helped the function of colchicine to improve the HSV induced BD-like
      symptoms by inhibiting the expression of NADPH oxidase in vivo mouse model.

PMID- 18823975
TI  - Differential involvement of cyclooxygenase isoforms in neutrophil migration in
      vivo and in vitro.
AB  - Pretreatment using celecoxib, a cyclooxygenase (COX) 2 inhibitor, or
      indomethacin, a nonselective COX inhibitor, reduced lypopolyssaccharide (LPS)
      induced leukocyte migration to the rat peritoneal cavity. The effect of celecoxib
      (12 mg/kg) or indomethacin (2 mg/kg) on neutrophil chemotaxis induced by formyl
      methionyl-leucyl-phenylalanine (FMLP) in an in vitro chemotactic assay (Boyden
      chamber) was investigated. Celecoxib and indomethacin inhibited chemotaxis
      induced by FMLP (Control=26.6+/-1.45, Celecoxib=12.8+/-3.04, Indomethacin=6.26+/
      2.19 cells/field). When observed under intravital microscopy, a mouse cremaster
      preparation was used to assess the microvasculature to further investigate which
      step of cell recruitment was affected by these drugs. Celecoxib and indomethacin
      inhibited leukocyte migration induced by 0.05 microg/kg LPS injected into the
      cremaster muscle. However, the effect of celecoxib was associated with reduced
      cell rolling and adhesion, whereas indomethacin was only effective at inhibiting
      cell adhesion. Furthermore, SC560 pretreatment (a COX-1 selective inhibitor) of
      normal or LPS-challenged tissues did not alter leukocyte migration or cell
      adhesion, but it did enhance leukocyte rolling activity in both cases. Taken
      together, these results indicate that: 1) COX-1 activity is mainly related to
      leukocyte traffic under physiological conditions, and 2) COX-2 activity is mainly
      related to cell traffic under inflammatory conditions in vascular beds,
      suggesting a possible effect of selective COX-2 inhibitors on the expression of
      adhesion molecules.

PMID- 18823976
TI  - Plasmodium falciparum: Activity of artemisinin against Plasmodium falciparum
      cultured in sickle trait hemoglobin AS and normal hemoglobin AA red blood cells.
AB  - The presence of sickle hemoglobin causes accumulation of hemoglobin degradative
      products that favor oxidative reaction in erythrocytes. Artemisinin derivatives
      exert antiparasite effects through oxidative reactions within infected
      erythrocytes. Using [(3)H]-hypoxanthine incorporation, we therefore did an in
      vitro comparison of IC(50) values for artemisinin in Plasmodium falciparum
      infected erythrocytes from sickle cell trait (AS) and normal (AA) individuals.
      IC(50) values for chloroquine served as control. Without drugs, parasite growth
      was similar in AA and AS erythrocytes. Gender, age and blood group of donors had
      no significant effects on parasite growth. IC(50) value for artemisinin was 27+/
      14nM in AS (N=22) compared to 24+/-9nM (N=27) in AA erythrocytes (P=0.4). IC(50)
      values for chloroquine were also similar in AA (22+/-8nM) and AS (20+/-11nM)
      erythrocytes. These results show no evidence of elevated artemisinin activity on
      P. falciparum in AS erythrocytes in vitro.

PMID- 18823977
TI  - Use of ProteinChip technology for identifying biomarkers of parasitic diseases:
      the example of porcine cysticercosis (Taenia solium).
AB  - Taenia solium cysticercosis is a significant public health problem in endemic
      countries. The current serodiagnostic techniques are not able to differentiate
      between infections with viable cysts and infections with degenerated cysts. The
      objectives of this study were to identify specific novel biomarkers of these
      different disease stages in the serum of experimentally infected pigs using
      ProteinChip technology (Bio-Rad) and to validate these biomarkers by analyzing
      serum samples from naturally infected pigs. In the experimental sample set 30
      discriminating biomarkers (p<0.05) were found, 13 specific for the viable
      phenotype, 9 specific for the degenerated phenotype and 8 specific for the
      infected phenotype (either viable or degenerated cysts). Only 3 of these
      biomarkers were also significant in the field samples; however, the peak profiles
      were not consistent among the two sample sets. Five biomarkers discovered in the
      sera from experimentally infected pigs were identified as clusterin, lecithin
      cholesterol acyltransferase, vitronectin, haptoglobin and apolipoprotein A-I.

PMID- 18823978
TI  - Matrix metalloproteinase-12 gene regulation by a PPAR alpha agonist in human
      monocyte-derived macrophages.
AB  - MMP-12, a macrophage-specific matrix metalloproteinase with large substrate
      specificity, has been reported to be highly expressed in mice, rabbits and human
      atherosclerotic lesions. Increased MMP-12 from inflammatory macrophages is
      associated with several degenerative diseases such as atherosclerosis. In this
      manuscript, we show that IL-1beta, a proinflammatory cytokine found in
      atherosclerotic plaques, increases both mRNA and protein levels of MMP-12 in
      human monocyte-derived macrophages (HMDM). Since peroxisome proliferator
      activated receptors (PPARs), such as PPARalpha and PPARgamma, are expressed in
      macrophages and because PPAR activation exerts an anti-inflammatory effect on
      vascular cells, we have investigated the effect of PPARalpha and gamma isoforms
      on MMP-12 regulation in HMDM. Our results show that MMP-12 expression (mRNA and
      protein) is down regulated in IL-1beta-treated macrophages only in the presence
      of a specific PPARalpha agonist, GW647, in a dose-dependent manner. In contrast,
      this inhibitory effect was abolished in IL-1beta-stimulated peritoneal
      macrophages isolated from PPARalpha(-/-) mice and treated with the PPARalpha
      agonist, GW647. Moreover, reporter gene transfection experiments using different
      MMP-12 promoter constructs showed a reduction of the promoter activities by
      approximately 50% in IL-1beta-stimulated PPARalpha-pre-treated cells. However,
      MMP-12 promoter analysis did not reveal the presence of a PPRE response element.
      The IL-1beta effect is known to be mediated through the AP-1 binding site.
      Mutation of the AP-1 site, located at -81 in the MMP-12 promoter region relative
      to the transcription start site, followed by transfection analysis, gel shift and
      ChIP experiments revealed that the inhibitory effect was the consequence of the
      protein-protein interaction between GW 647-activated PPARalpha and c-Fos or c-Jun
      transcription factors, leading to inhibition of their binding to the AP-1 motif.
      These studies suggest that PPARalpha agonists may be used therapeutically, not
      only for lipid disorders, but also to prevent inflammation and atheromatous
      plaque rupture, where their ability to inhibit MMP-12 expression in HMDM may be
      beneficial.

PMID- 18823979
TI  - The reproductive biology of male cottonmouths (Agkistrodon piscivorus): do plasma
      steroid hormones predict the mating season?
AB  - To better understand the proximate causation of the two major types of mating
      seasons described for North American pitvipers, we conducted a field study of the
      cottonmouth (Agkistrodon piscivorus) in Georgia from September 2003 to May 2005
      that included an extensive observational regime and collection of tissues for
      behavioral, anatomical, histological, and hormone analysis. Enzyme immunoassays
      (EIA) of plasma samples and standard histological procedures were conducted on
      reproductive tissues. Evidence from the annual testosterone (T) and sexual
      segment of the kidney (SSK) cycle and their relationship to the spermatogenic
      cycle provide correlative evidence of a unimodal mating pattern in this species
      of pitviper, as these variables consistently predict the mating season in all
      snake species previously examined under natural conditions. In most reptiles
      studied to date, high plasma levels of T and corticosterone (CORT) coincide
      during the mating period, making the cottonmouth an exception to this trend; we
      suggest two possible explanations for increased CORT during spring (regulation of
      a spring basking period), and decreased CORT during summer (avoiding reproductive
      behavioral inhibition), in this species.

PMID- 18823980
TI  - Trypanosoma cruzi: Induction of benznidazole resistance in vivo and its
      modulation by in vitro culturing and mice infection.
AB  - Through a continuous in vivo drug pressure protocol, using mice as experimental
      model, we induced benznidazole resistance in Trypanosoma cruzi stocks. Full
      resistance was obtained for four out of five T. cruzi stocks analyzed. However,
      the number of benznidazole doses (40-180), as well as the time (4-18 months)
      necessary to induce resistance varied among the different T. cruzi stocks. The
      resistance phenotype remained stable after T. cruzi stocks has been maintained by
      12 passages in mice (six months) and in acellular culture for the same time.
      However, the maintenance of resistant parasite for 12 months in acellular culture
      induces a reduction in its level of benznidazole resistance, while no alteration
      was detected in parasite maintained for the same time in mice. The data showed
      the stability of the resistance acquired by drug pressure, but suggest the
      possibility of reversible changes in the resistance levels after maintenance for
      long time in acellular culture.

PMID- 18823981
TI  - Toxoplasma gondii: effects of neuwiedase, a metalloproteinase from Bothrops
      neuwiedi snake venom, on the invasion and replication of human fibroblasts in
      vitro.
AB  - The major aim to the present study was to determine the effects of neuwiedase, a
      metalloproteinase isolated from Bothrops neuwiedi snake venom, on invasion and
      replication of Toxoplasma gondii in human fibroblasts in vitro. Neuwiedase
      treatment was done on host cells previously infected with T. gondii or on
      parasite before fibroblast infection. When treatments were done after or before
      infection, infection rates were inhibited in 71% and 61%, respectively.
      Considering that therapy protocols currently used in T. gondii infection cause
      considerable side effects, particularly in immunocompromised individuals and
      pregnant women, the results of neuwiedase treatment described herein could be
      taken into account for the development of new synthetic therapeutic agents,
      mainly due to the capacity of this enzyme to degrade extracellular matrix
      components, such as laminin, fibronectin and type I collagen, which is important
      to interfere in T. gondii host cell invasion.

PMID- 18823982
TI  - Acetylcholine receptor subunit genes from Ancylostoma caninum: altered
      transcription patterns associated with pyrantel resistance.
AB  - The molecular mechanism of resistance to nicotinic agonist anthelmintics such as
      pyrantel and levamisole in nematodes of medical and veterinary significance is
      poorly understood. The identification of pyrantel-resistant isolates of the
      canine hookworm, Ancylostoma caninum, provides an opportunity to explore, at a
      molecular level, the mechanism of cholinergic resistance in a species that is a
      model for the human hookworms. Here we describe the cloning of three A. caninum
      genes orthologous to components of the pyrantel-sensitive nicotinic acetylcholine
      receptor in Caenorhabditis elegans (UNC-29, -38, -63). Analysis of mRNA levels by
      quantitative PCR was also performed on these genes, plus an additional three
      nicotinic acetylcholine receptor subunit genes thought not to be constituents of
      the pyrantel-sensitive receptor, for which a partial sequence was obtained. Gene
      sequences and mRNA levels were compared between two isolates of A. caninum
      showing either high- or low-level resistance to pyrantel (as shown previously by
      in vivo efficacy and in vitro comparative studies). While no polymorphisms of
      likely significance between the two A. caninum isolates were observed,
      quantitative analysis of transcription revealed significantly lower levels for
      the three putative pyrantel receptor subunits (AAR-29, -38 and -63) in the highly
      pyrantel-resistant isolate compared with the isolate with low-level resistance.
      In contrast, transcription of the three subunits thought not to constitute the
      pyrantel receptor (AAR-8, -15 and -19) was either not significantly different
      between the two isolates, or slightly higher in the highly-resistant isolate.
      This data suggests that reduced transcription of the mRNA coding for nicotinic
      acetylcholine receptor subunits that form the pyrantel-sensitive receptors may be
      a component of the pyrantel resistance mechanism in A. caninum.

PMID- 18823983
TI  - The fully oxidized form of the cytochrome bd quinol oxidase from E. coli does not
      participate in the catalytic cycle: direct evidence from rapid kinetics studies.
AB  - Cytochrome bd catalyzes the two-electron oxidation of either ubiquinol or
      menaquinol and the four-electron reduction of O(2) to H(2)O. In the current work,
      the rates of reduction of the fully oxidized and oxoferryl forms of the enzyme by
      the 2-electron donor ubiquinol-1 and single electron donor N,N,N',N'-tetramethyl
      p-phenylendiamine (TMPD) have been examined by stopped-flow techniques. Reduction
      of the all-ferric form of the enzyme is 1000-fold slower than required for a step
      in the catalytic cycle, whereas the observed rates of reduction of the oxoferryl
      and singly-reduced forms of the cytochrome are consistent with the catalytic
      turnover. The data support models of the catalytic cycle which do not include the
      fully oxidized form of the enzyme as an intermediate.

PMID- 18823984
TI  - Oxidative burst assessment and neutrophil-platelet complexes in unlysed whole
      blood.
AB  - BACKGROUND: Methods currently employed for measuring reactive oxygen species
      production can lead to both cellular depletion and in artifactual activation. The
      objective of this study was to design a methodology allowing the measurement of
      oxidative burst (OB) with minimal sample manipulation. METHODS: To that purpose a
      flow cytometry technique developed in our laboratory, based on nucleic acid
      staining to discriminate erythrocytes and debris, was employed. DRAQ5 dye and
      PECy5-CD45 monoclonal antibody (MoAb) were simultaneously used in FL3 to identify
      the leukocyte population and the PE-CD14 MoAb emission was detected in FL2 for
      monocytes. OB was measured by using the fluorogenic probe dihydrorhodamine 123, a
      marker of hydrogen peroxide production. Phorbol myristate acetate (PMA),
      Opsonized Zymosan (OZ), fMLP and calcium ionophore A23187 activators were also
      used in this study. For OB assays, dose-response curves were performed for each
      activator. In addition, the effect of activator concentration on annexin V
      binding, as a measure of phosphatidylserine translocation, was evaluated.
      RESULTS: With this method no-lysis and no-wash steps are required, thus avoiding
      an unwanted damage to leukocytes. PMA and Zymosan produced an increase in annexin
      V binding, while fMLP and calcium ionophore did not. CONCLUSIONS: This study
      reports a feasible and reproducible new flow cytometry assay for assessing OB of
      neutrophils and monocytes with minimal sample manipulation. In addition, under
      PMA and OZ conditions, the number of neutrophils showing annexin V binding was
      strikingly increased. This effect is not related with a phagocytic
      overstimulation, but with an increased neutrophil-platelet complexes formation.

PMID- 18823985
TI  - Hepatic stellate cells secrete angiopoietin 1 that induces angiogenesis in liver
      fibrosis.
AB  - BACKGROUND & AIMS: Although angiogenesis is closely associated with liver
      fibrosis, the angiogenic factors involved in liver fibrosis are not well
      characterized. Angiopoietin 1 is an angiogenic cytokine indispensable for
      vascular development and remodeling. It functions as an agonist for the receptor
      tyrosine kinase with immunoglobulin G-like and endothelial growth factor-like
      domains 2 (Tie2) and counteracts apoptosis, promotes vascular sprouting or
      branching, and stabilizes vessels. METHODS: Liver samples from patients with
      liver fibrosis were evaluated for mRNA expression of angiogenic cytokines. Liver
      fibrosis was induced in BALB/c mice by either carbon tetrachloride (CCl(4)) or
      bile duct ligation (BDL). Hepatic stellate cells (HSCs) were isolated from BALB/c
      mice. We used an adenovirus expressing the extracellular domain of Tie2 (AdsTie2)
      to block angiopoietin signaling in mice and evaluated its effect on liver
      fibrosis. RESULTS: mRNA expression level of angiopoietin 1 was increased in human
      fibrotic livers and correlated with the expression level of CD31, an endothelial
      cell marker. During experimental models of murine liver fibrosis, angiopoietin 1
      was expressed by activated HSCs. In primary cultures, activated HSCs express and
      secrete angiopoietin 1 more abundantly than quiescent HSCs, and the inflammatory
      cytokine tumor necrosis factor-alpha stimulates its expression in an nuclear
      factor-kappaB-dependent manner. AdsTie2 inhibits angiogenesis and liver fibrosis
      induced by either CCl(4) or BDL. CONCLUSIONS: These results reveal an angiogenic
      role of HSCs mediated by angiopoietin 1, which contributes to development of
      liver fibrosis. Thus, angiogenesis and hepatic fibrosis are mutually stimulatory,
      such that fibrosis requires angiogenesis and angiogenesis requires angiopoietin 1
      from activated HSCs.

PMID- 18823986
TI  - Lower gastrointestinal events in a double-blind trial of the cyclo-oxygenase-2
      selective inhibitor etoricoxib and the traditional nonsteroidal anti-inflammatory
      drug diclofenac.
AB  - BACKGROUND & AIMS: Nonsteroidal anti-inflammatory drugs (NSAIDs) cause lower
      gastrointestinal (GI) clinical events such as bleeding. Cyclo-oxygenase (COX)-2
      selective inhibitors decrease upper GI events, but no prospective trial has
      prespecified assessment of lower GI clinical events. METHODS: Patients >or=50
      years old with osteoarthritis or rheumatoid arthritis were randomly assigned to
      etoricoxib (60 or 90 mg qd) or diclofenac (150 mg qd). Lower GI clinical events,
      confirmed by a blinded adjudication committee, included perforation or
      obstruction requiring hospitalization or bleeding (gross or occult rectal
      bleeding without upper GI cause associated with hypotension, orthostatic changes
      in heart rate [>20 beats per minute] or blood pressure [>20 mmHg systolic or >10
      mmHg diastolic], hemoglobin drop >or=2 g/dl, or transfusion; or observed active
      bleeding or stigmata of hemorrhage). RESULTS: We enrolled 34,701 patients with
      mean duration of therapy of 18 months. Rates were 0.32 and 0.38 lower GI clinical
      events per 100 patient-years for etoricoxib and diclofenac (hazard ratio [HR] =
      0.84; 95% confidence interval [CI], 0.63-1.13). Bleeding was the most common
      event (rates of 0.19 and 0.23 per 100 patient-years, respectively). Multivariable
      analysis revealed significant risk factors to be prior lower GI event (HR = 4.06;
      95% CI, 2.93-5.62) and age >or=65 years (HR = 1.98; 95% CI, 1.45-2.71).
      CONCLUSIONS: A statistically significant decrease in lower GI clinical events was
      not seen with the COX-2 selective inhibitor etoricoxib versus the traditional
      NSAID diclofenac. The risk of a lower GI clinical event with NSAID use seems to
      be constant over time, and the major risk factors are a prior lower GI event and
      older age.

PMID- 18823987
TI  - Meta-analysis of the placebo rates of clinical relapse and severe endoscopic
      recurrence in postoperative Crohn's disease.
AB  - BACKGROUNDS & AIMS: The benefit of therapy for prevention of postoperative
      recurrence of Crohn's disease (CD) is limited. Clinical relapse and severe
      endoscopic recurrence are the main outcomes in the evaluation of trials on
      prevention of recurrence. The aim of this meta-analysis was to focus on knowledge
      of the placebo rates of relapse and recurrence in postoperative CD and to
      identify factors influencing these rates. METHODS: We performed a meta-analysis
      of placebo-controlled, randomized clinical trials, evaluating therapies for
      postoperative maintenance of CD identified on MEDLINE from 1990 to 2006. Primary
      outcomes were clinical relapse and severe endoscopic recurrence. RESULTS: The
      pooled estimate of the placebo relapse rate was 23.7% (95% confidence interval
      [CI], 13-35; range 0-78). There was a statistically significant heterogeneity
      among studies (P < .0001). Heterogeneity in clinical relapse was present even if
      the trials were stratified according to the time of outcome. The pooled estimate
      of the severe endoscopic recurrence rate was 50.2% (95% CI, 28-73; range, 30-79).
      There was significant heterogeneity among the studies (P = .00038). This
      heterogeneity was less apparent in studies carried out within 12 months. The
      logistic analysis identified only duration of follow-up as a variable associated
      with different placebo relapse rates. No variable was identified as a predictor
      of a placebo endoscopic recurrence rate. CONCLUSIONS: There is significant
      heterogeneity among placebo rates in postoperative CD. No single design variable
      was identified that explained the heterogeneity in placebo outcomes for clinical
      or endoscopic recurrence.

PMID- 18823988
TI  - Pathogenecity of a baculovirus isolated from Arctornis submarginata (Walker)
      (Lepidoptera:Lymantriidae), a potential pest of tea growing in the Darjeeling
      foothills of India.
AB  - A granulosis virus (GV) was isolated from the diseased caterpillars of Arctornis
      submarginata (Walker) (Lymantriidae), a defoliating pest of tea from Darjeeling
      foothill region. The phase contrast and transmission electron microscopic studies
      identified the virus as granulosis virus. SDS-PAGE analysis of major protein of
      the occlusion bodies was found to be 31 kDa, characteristic for granulin. The
      total genomic DNA was isolated. The major band found was of molecular weight 16
      kDa. Bioassay conducted with the occlusion bodies (OBs) of the virus showed
      LC(50) value of 4.46 x 10(4) OBs/ml for the second instar caterpillars. Median
      lethal time (LT(50)) were 6.6 days for 1 x 10(4)OBs/ml, 5.09 days for 1 x 10(5)
      OBs/ml, 4.45 days for 1 x 10(6) OBs/ml and 3.87 days for 1 x 10(7) OBs/ml
      concentrations. The results indicated the potential of the virus for its future
      application as microbial pesticide against A. submarginata in future.

PMID- 18823989
TI  - Anoretic effects of neuropeptide FF are mediated via central mu and kappa
      subtypes of opioid receptors and receptor ligands.
AB  - Recently, we demonstrated that neuropeptide FF (NPFF) causes anorexigenic effects
      in chicks that were associated with the hypothalamus. The present study was
      designed to better understand some of the central mechanisms that mediate these
      effects. Co-injection of NPFF and beta-funaltrexamine (FNA, a mu opioid receptor
      antagonist) did not suppress food intake more than when NPFF and FNA were
      injected alone. However, co-injection of NPFF and ICI-174,864 (ICI, a delta
      opioid receptor antagonist) caused a greater reduction in food intake than when
      NPFF and ICI were injected alone. Co-injection of NPFF and nor-binaltorphimine
      (BNI, a kappa opioid receptor antagonist) did not cause a greater suppression of
      food intake than when NPFF and BNI were injected alone. Hyperphagia induced by
      neuropeptide Y and beta-endorphin (both ligands of opioid receptors) was reversed
      by NPFF. These results suggest that NPFF-induced satiety has a relationship with
      mu and kappa but not delta subtypes of opioid receptors, and since NPFF does not
      bind opioid receptors itself NPFF-associated satiety is likely mediated by
      effects on opioid receptor ligands such as NPY and beta-endorphin. Thus, NPFF
      induced satiety may be mediated via modulation of the chick's innate opioid
      associated orexigenic system.

PMID- 18823990
TI  - Calpain mediates cardiac troponin degradation and contractile dysfunction in
      atrial fibrillation.
AB  - The self-perpetuation of atrial fibrillation (AF) is associated with atrial
      remodeling, including the degradation of the myofibril structure (myolysis).
      Myolysis is related to AF-induced activation of cysteine proteases and underlies
      loss of contractile function. In this study, we investigated which proteases are
      involved in the degradation of myofibrillar proteins during AF and whether their
      inhibition leads to preservation of contractile function after AF. In tachypaced
      HL-1 cardiomyocytes and atrial tissue from AF and control patients, degradation
      of myofibrillar proteins troponin (cTn) T, I, C, human cTnT and actin was
      investigated by Western blotting, and contractile function was analyzed by cell
      shortening measurements. The role of major proteases was determined by applying
      specific inhibitors. Tachypacing of HL-1 cardiomyocytes induced a gradual and
      significant degradation of cTns but not actin, and caused contractile
      dysfunction. Both were prevented by inhibition of calpain but not by inhibition
      of caspases or the proteasome. In patients with persistent AF, a significant
      degradation of cTnT, cTnI and cTnC was found compared to sinus rhythm or
      paroxysmal AF, which correlated significantly with both calpain activity and the
      amount of myolysis. Additionally, by utilizing tachypaced human cTnT-transfected
      HL-1 cardiomyocytes, we directly showed that the degradation of human cTnT was
      mediated by calpain and not by caspases or proteasome. Our results suggest that
      calpain inhibition may therefore represent a key target in combating AF-related
      structural and functional remodeling.

PMID- 18823991
TI  - Testing on formalin-fixed neutrophils is less sensitive and specific for small
      vessel vasculitis, and less sensitive for MPO-ANCA, than most ELISAs.
AB  - This study evaluated the usefulness of testing sera with perinuclear
      antineutrophil cytoplasmic antibodies (P-ANCA) on formalin-fixed neutrophils to
      differentiate between vasculitis and other diseases, and to distinguish between
      myeloperoxidase (MPO) and other antigen targets. Sera from active (n=24) or
      treated vasculitis (n=23) and non-vasculitic disease (n=37) were tested in 3
      ethanol- and 2 formalin-fixed neutrophil assays, and in 12 MPO-ANCA ELISAs. The
      sensitivity of demonstrating that P-ANCA became cytoplasmic on formalin-fixed
      cells in vasculitis, and negative in non-vasculitic disease was 75-79% in
      different assays compared with 88% for positivity in the majority of MPO-ANCA
      ELISAs. The sensitivity and specificity of demonstrating that P-ANCA became
      cytoplasmic where the target was MPO, and disappeared with other antigens were
      89% and 74-80% respectively in different assays. P-ANCA specificity for MPO
      should be confirmed in one of the better-performing MPO-ANCA ELISAs.

PMID- 18823993
TI  - Allophycocyanin trimer stability and functionality are primarily due to polar
      enhanced hydrophobicity of the phycocyanobilin binding pocket.
AB  - Allophycocyanin (APC) is the primary pigment-protein component of the cores of
      the phycobilisome antenna complex. In addition to an extremely high degree of
      amino acid sequence conservation, the overall structures of APC from both
      mesophilic and thermophilic species are almost identical at all levels of
      assembly, yet APC from thermophilic organisms should have structural attributes
      that prevent thermally induced denaturation. We determined the structure of APC
      from the thermophilic cyanobacterium Thermosynechococcus vulcanus to 2.9 A,
      reaffirming the conservation of structural similarity with APC from mesophiles.
      We provide spectroscopic evidence that T. vulcanus APC is indeed more stable at
      elevated temperatures in vitro, when compared with the APC from mesophilic
      species. APC thermal and chemical stability levels are further enhanced when
      monitored in the presence of high concentrations of buffered phosphate, which
      increases the strength of hydrophobic interactions, and may mimic the effect of
      cytosolic crowding. Absorption spectroscopy, size-exclusion HPLC, and native gel
      electrophoresis also show that the thermally or chemically induced changes in the
      APC absorption spectra that result in the loss of the prominent 652-nm band in
      trimeric APC are not a result of physical monomerization. We propose that the
      bathochromic shift that occurs in APC upon trimerization is due to the coupling
      of the hydrophobicity of the alpha84 phycocyanobilin cofactor environment created
      by a deep cleft formed by the beta subunit with highly charged flanking regions.
      This arrangement also provides the additional stability required by thermophiles
      at elevated temperatures. The chemical environment that induces the bathochromic
      shift in APC trimers is different from the source of shifts in the absorption of
      monomers of the terminal energy acceptors APC(B) and L(CM), as visualized by the
      building of molecular models.

PMID- 18823992
TI  - Molecular basis for proline- and arginine-rich peptide inhibition of proteasome.
AB  - PR39, a naturally occurring and cell-permeable proline- and arginine-rich
      peptide, blocks the degradation of inhibitor of nuclear factor kappaB
      (IkappaBalpha), thereby attenuating inflammation. It is a noncompetitive and
      reversible inhibitor of 20S proteasome. To identify its basis of action, we used
      solution NMR spectroscopy and mutational analyses of the active fragment, PR11,
      which identified amino acids required for human 20S proteasome inhibiting
      activity. We then examined PR11-mediated changes in the expression of nuclear
      factor kappaB-dependent genes in situ. The results provide prerequisites for
      proteasome inhibition by proline- and arginine-rich peptides, providing a
      powerful new tool to investigate inflammatory processes. These findings offer new
      leads in developing drugs to treat heart diseases or stroke.

PMID- 18823994
TI  - Probing possible downhill folding: native contact topology likely places a
      significant constraint on the folding cooperativity of proteins with
      approximately 40 residues.
AB  - Experiments point to appreciable variations in folding cooperativity among
      natural proteins with approximately 40 residues, indicating that the behaviors of
      these proteins are valuable for delineating the contributing factors to
      cooperative folding. To explore the role of native topology in a protein's
      propensity to fold cooperatively and how native topology might constrain the
      degree of cooperativity achievable by a given set of physical interactions, we
      compared folding/unfolding kinetics simulated using three classes of native
      centric C(alpha) chain models with different interaction schemes. The approach
      was applied to two homologous 45-residue fragments from the peripheral subunit
      binding domain family and a 39-residue fragment of the N-terminal domain of
      ribosomal protein L9. Free-energy profiles as functions of native contact number
      were computed to assess the heights of thermodynamic barriers to folding. In
      addition, chevron plots of folding/unfolding rates were constructed as functions
      of native stability to facilitate comparison with available experimental data.
      Although common Go-like models with pairwise Lennard-Jones-type interactions
      generally fold less cooperatively than real proteins, the rank ordering of
      cooperativity predicted by these models is consistent with experiment for the
      proteins investigated, showing increasing folding cooperativity with increasing
      nonlocality of a protein's native contacts. Models that account for water
      expulsion (desolvation) barriers and models with many-body (nonadditive)
      interactions generally entail higher degrees of folding cooperativity indicated
      by more linear model chevron plots, but the rank ordering of cooperativity
      remains unchanged. A robust, experimentally valid rank ordering of model folding
      cooperativity independent of the multiple native-centric interaction schemes
      tested here argues that native topology places significant constraints on how
      cooperatively a protein can fold.

PMID- 18823995
TI  - Histidine kinase regulation by a cyclophilin-like inhibitor.
AB  - The sensor histidine kinase A (KinA) from Bacillus subtilis triggers a
      phosphorelay that activates sporulation. The antikinase KipI prevents sporulation
      by binding KinA and inhibiting the autophosphorylation reaction. Using neutron
      contrast variation, mutagenesis, and fluorescence data, we show that two KipI
      monomers bind via their C-domains at a conserved proline in the KinA dimerization
      and histidine-phosphotransfer (DHp) domain. Our crystal structure of the KipI C
      domain reveals the binding motif has a distinctive hydrophobic groove formed by a
      five-stranded antiparallel beta-sheet; a characteristic of the cyclophilin family
      of proteins that bind prolines and often act as cis-trans peptidyl-prolyl
      isomerases. We propose that the DHp domain of KinA transmits conformational
      signals to regulate kinase activity via this proline-mediated interaction. Given
      that both KinA and KipI homologues are widespread in the bacterial kingdom, this
      mechanism has broad significance in bacterial signal transduction.

PMID- 18823996
TI  - The 1.8-A crystal structure of alpha1-acid glycoprotein (Orosomucoid) solved by
      UV RIP reveals the broad drug-binding activity of this human plasma lipocalin.
AB  - Alpha(1)-acid glycoprotein (AGP) is an important drug-binding protein in human
      plasma and, as an acute-phase protein, it has a strong influence on
      pharmacokinetics and pharmacodynamics of many pharmaceuticals. We report the
      crystal structure of the recombinant unglycosylated human AGP at 1.8 A
      resolution, which was solved using the new method of UV-radiation-damage-induced
      phasing (UV RIP). AGP reveals a typical lipocalin fold comprising an eight
      stranded beta-barrel. Of the four loops that form the entrance to the ligand
      binding site, loop 1, which connects beta-strands A and B, is among the longest
      observed so far and exhibits two full turns of an alpha-helix. Furthermore, it
      carries one of the five N-linked glycosylation sites, while a second one occurs
      underneath the tip of loop 2. The branched, partly hydrophobic, and partly acidic
      cavity, together with the presumably flexible loop 1 and the two sugar side
      chains at its entrance, explains the diverse ligand spectrum of AGP, which is
      known to vary with changes in glycosylation pattern.

PMID- 18823997
TI  - Assembling the human IFN-beta enhanceosome in solution.
AB  - Assembly of interferon-beta enhanceosome from its individual protein components
      and of enhancer DNA has been studied in solution using a combination of
      fluorescence anisotropy, microcalorimetry, and CD titration. It was shown that
      the enhancer binds only one full-length phosphomimetic IRF-3 dimer at the PRDIII
      PRDI sites, and this binding does not exhibit cooperativity with binding of the
      ATF-2/c-Jun bZIP (leucine zipper dimer with basic DNA recognition segments)
      heterodimer at the PRDIV site. The orientation of the bZIP pair is, therefore,
      not determined by the presence of the IRF-3 dimer, but is predetermined by the
      asymmetry of the PRDIV site. In contrast, bound IRF-3 dimer interacts strongly
      with the NF-kappaB (p50/p65) heterodimer bound at the neighboring PRDII site. The
      orientation of bound NF-kappaB is also predetermined by the asymmetry of the
      PRDII site and is the opposite of that found in the crystal structure. The HMG
      I/Y protein, proposed as orchestrating enhanceosome assembly, interacts
      specifically with the PRDII site of the interferon-beta enhancer by inserting its
      DNA-binding segments (AT hooks) into the minor groove, resulting in a significant
      increase in NF-kappaB binding affinity for the major groove of this site.

PMID- 18823998
TI  - Time evolution of the quaternary structure of Escherichia coli aspartate
      transcarbamoylase upon reaction with the natural substrates and a slow, tight
      binding inhibitor.
AB  - Here, we present a study of the conformational changes of the quaternary
      structure of Escherichia coli aspartate transcarbamoylase, as monitored by time
      resolved small-angle X-ray scattering, upon combining with substrates, substrate
      analogs, and nucleotide effectors at temperatures between 5 and 22 degrees C,
      obviating the need for ethylene glycol. Time-resolved small-angle X-ray
      scattering time courses tracking the T-->R structural change after mixing with
      substrates or substrate analogs appeared to be a single phase under some
      conditions and biphasic under other conditions, which we ascribe to multiple
      ligation states producing a time course composed of multiple rates. Increasing
      the concentration of substrates up to a certain point increased the T-->R
      transition rate, with no further increase in rate beyond that point. Most
      strikingly, after addition of N-phosphonacetyl-l-aspartate to the enzyme, the
      transition rate was more than 1 order of magnitude slower than with the natural
      substrates. These results on the homotropic mechanism are consistent with a
      concerted transition between structural and functional states of either low
      affinity, low activity or high affinity, high activity for aspartate. Addition of
      ATP along with the substrates increased the rate of the transition from the T to
      the R state and also decreased the duration of the R-state steady-state phase.
      Addition of CTP or the combination of CTP/UTP to the substrates significantly
      decreased the rate of the T-->R transition and caused a shift in the enzyme
      population towards the T state even at saturating substrate concentrations. These
      results on the heterotropic mechanism suggest a destabilization of the T state by
      ATP and a destabilization of the R state by CTP and CTP/UTP, consistent with the
      T and R state crystallographic structures of aspartate transcarbamoylase in the
      presence of the heterotropic effectors.

PMID- 18823999
TI  - First record of Perkinsus olseni, a protozoan parasite infecting the commercial
      clam Ruditapes decussatus in Spanish Mediterranean waters.
AB  - We present the first record in Spanish Mediterranean waters of the protozoan
      parasite Perkinsus olseni infecting the clam Ruditapes decussatus. Perkinsus
      infection was detected all year around albeit at a low level of infection
      intensity. Histological analysis, induction of zoospores and in situ
      hybridisation assay confirmed the presence of Perkinsus sp. The identity of the
      parasite was determined by species-specific PCR assay in DNA samples obtained
      from infected clams. Sequencing of amplified fragments showed 100% identity to
      the ITS region of P. olseni. We confirmed for the first time the presence of P.
      olseni in Spanish Mediterranean waters.

PMID- 18824001
TI  - Striatal 5-HT1A receptor stimulation reduces D1 receptor-induced dyskinesia and
      improves movement in the hemiparkinsonian rat.
AB  - Convergent evidence suggests that serotonin 5-HT1A receptor (5-HT1AR) agonists
      reduce l-DOPA-induced dyskinesia by auto-regulating aberrant release of l-DOPA
      derived dopamine (DA) from raphestriatal neurons. However, recent findings
      indicate that 5-HT1AR stimulation also modifies D1 receptor (D1R)-mediated
      dyskinesia and rotations implicating a previously unexplored extra-raphe
      mechanism. In order to characterize the contribution of the striatum to these
      effects, rats with medial forebrain bundle DA lesions were tested for abnormal
      involuntary movements (AIMs) and rotations following striatal microinfusions of
      the 5-HT1AR agonist +/-8-OH-DPAT and systemic D1R agonist treatment with
      SKF81297. Additional rats with multi-site striatal DA lesions were tested for
      motor disability following systemic or intrastriatal +/-8-OH-DPAT with or without
      systemic SKF81297. In rats with medial forebrain bundle lesions, striatal
      infusions of +/-8-OH-DPAT dose-dependently reduced AIMs while conversely
      increasing rotations. In rats with striatal lesions, +/-8-OH-DPAT alone, both
      systemic and intrastriatal administration, optimally reversed motor disability.
      Collectively, these results support an important functional interaction between 5
      HT1AR and D1R in the striatum with implications for the improved treatment of
      Parkinson's disease.

PMID- 18824002
TI  - Several major antiepileptic drugs are substrates for human P-glycoprotein.
AB  - One of the current hypotheses of pharmacoresistant epilepsy proposes that
      transport of antiepileptic drugs (AEDs) by drug efflux transporters such as P
      glycoprotein (Pgp) at the blood-brain barrier may play a significant role in
      pharmacoresistance in epilepsy by extruding AEDs from their intended site of
      action. However, several recent in vitro studies using cell lines that
      overexpress efflux transporters indicate that human Pgp may not transport AEDs to
      any relevant extent. In this respect it has to be considered that most AEDs are
      highly permeable, so that conventional bi-directional transport assays as used in
      these previous studies may fail to identify AEDs as Pgp substrates, particularly
      if these drugs are not high-affinity substrates for Pgp. In the present study, we
      used a modified transport assay that allows evaluating active transport
      independently of the passive permeability component. In this concentration
      equilibrium transport assay (CETA), the drug is initially added at identical
      concentration to both sides of a polarized, Pgp-overexpressing cell monolayer
      instead of applying the drug to either the apical or basolateral side for
      studying bi-directional transport. Direct comparison of the conventional bi
      directional (concentration gradient) assay with the CETA, using MDR1-transfected
      LLC cells, demonstrated that CETA, but not the conventional assay, identified
      phenytoin and phenobarbital as substrates of human Pgp. Furthermore, directional
      transport was determined for lamotrigine and levetiracetam, but not
      carbamazepine. Transport of AEDs could be completely or partially (>50%)
      inhibited by the selective Pgp inhibitor, tariquidar. However, transport of
      phenobarbital and levetiracetam was also inhibited by MK571, which preferentially
      blocks transport by multidrug resistance transporters (MRPs), indicating that, in
      addition to Pgp, these AEDs are substrates of MRPs. The present study provides
      the first direct evidence that several AEDS are substrates of human Pgp, thus
      further substantiating the transporter hypothesis of pharmacoresistant epilepsy.

PMID- 18824000
TI  - How the serotonin story is being rewritten by new gene-based discoveries
      principally related to SLC6A4, the serotonin transporter gene, which functions to
      influence all cellular serotonin systems.
AB  - Discovered and crystallized over sixty years ago, serotonin's important functions
      in the brain and body were identified over the ensuing years by neurochemical,
      physiological and pharmacological investigations. This 2008 M. Rapport Memorial
      Serotonin Review focuses on some of the most recent discoveries involving
      serotonin that are based on genetic methodologies. These include examples of the
      consequences that result from direct serotonergic gene manipulation (gene
      deletion or overexpression) in mice and other species; an evaluation of some
      phenotypes related to functional human serotonergic gene variants, particularly
      in SLC6A4, the serotonin transporter gene; and finally, a consideration of the
      pharmacogenomics of serotonergic drugs with respect to both their therapeutic
      actions and side effects. The serotonin transporter (SERT) has been the most
      comprehensively studied of the serotonin system molecular components, and will be
      the primary focus of this review. We provide in-depth examples of gene-based
      discoveries primarily related to SLC6A4 that have clarified serotonin's many
      important homeostatic functions in humans, non-human primates, mice and other
      species.

PMID- 18824003
TI  - Atomistic simulations of the effects of polyglutamine chain length and solvent
      quality on conformational equilibria and spontaneous homodimerization.
AB  - Aggregation of expanded polyglutamine tracts is associated with nine different
      neurodegenerative diseases, including Huntington's disease. Experiments and
      computer simulations have demonstrated that monomeric forms of polyglutamine
      molecules sample heterogeneous sets of collapsed structures in water. The current
      work focuses on a mechanistic characterization of polyglutamine homodimerization
      as a function of chain length and temperature. These studies were carried out
      using molecular simulations based on a recently developed continuum solvation
      model that was designed for studying conformational and binding equilibria of
      intrinsically disordered molecules such as polyglutamine systems. The main
      results are as follows: Polyglutamine molecules form disordered, collapsed
      globules in aqueous solution. These molecules spontaneously associate at
      conditions approaching those of typical in vitro experiments for chains of length
      N>/=15. The spontaneity of these homotypic associations increases with increasing
      chain length and decreases with increasing temperature. Similar and generic
      driving forces govern both collapse and spontaneous homodimerization of
      polyglutamine in aqueous milieus. Collapse and dimerization maximize self
      interactions and reduce the interface between polyglutamine molecules and the
      surrounding solvent. Other than these generic considerations, there do not appear
      to be any specific structural requirements for either chain collapse or chain
      dimerization; that is, both collapse and dimerization are nonspecific in that
      disordered globules form disordered dimers. In fact, it is shown that the driving
      force for intermolecular associations is governed by spontaneous conformational
      fluctuations within monomeric polyglutamine. These results suggest that
      polyglutamine aggregation is unlikely to follow a homogeneous nucleation
      mechanism with the monomer as the critical nucleus. Instead, the results support
      the formation of disordered, non-beta-sheet-like soluble molten oligomers as
      early intermediates--a proposal that is congruent with recent experimental data.

PMID- 18824004
TI  - Structure of bacterial glutathione-S-transferase maleyl pyruvate isomerase and
      implications for mechanism of isomerisation.
AB  - Maleyl pyruvate isomerase (MPI) is a bacterial glutathione S-transferase (GST)
      from the pathway for degradation of naphthalene via gentisate that enables the
      bacterium Ralstonia to use polyaromatic hydrocarbons as a sole carbon source.
      Genome sequencing projects have revealed the presence of large numbers of GSTs in
      bacterial genomes, often located within gene clusters encoding the degradation of
      different aromatic compounds. This structure is therefore an example of this
      under-represented class of enzymes. Unlike many glutathione transferases, the
      reaction catalysed by MPI is an isomerisation of an aromatic ring breakdown
      product, and glutathione is a true cofactor rather than a substrate in the
      reaction. We have solved the structure of the enzyme in complex with
      dicarboxyethyl glutathione, an analogue of a proposed reaction intermediate, at a
      resolution of 1.3 A. The structure provides direct evidence that the glutathione
      thiolate attacks the substrate in the C2 position, with the terminal carboxylate
      buried at the base of the active site cleft. Our structures suggest that the C1
      C2 bond remains fixed so when rotation occurs around the C2-C3 bond the atoms
      from C4 onwards actually move. We identified a conserved arginine that is likely
      to stabilize the enolate form of the substrate during the isomerisation.
      Arginines at either side of the active site cleft can interact with the end of
      the substrate/product and preferentially stabilise the product. MPI has
      significant sequence similarity to maleylacetoacetate isomerase (MAAI), which
      performs an analogous reaction in the catabolism of phenylalanine and tyrosine.
      The proposed mechanism therefore has relevance to the MAAIs. Significantly,
      whilst the overall sequence identity is 40% only one of the five residues from
      the Zeta motif in the active site is conserved. We re-examined the roles of the
      residues in the active site of both enzymes and the Zeta motif itself.

PMID- 18824005
TI  - Structural details of HIV-1 recognition by the broadly neutralizing monoclonal
      antibody 2F5: epitope conformation, antigen-recognition loop mobility, and anion
      binding site.
AB  - 2F5 is a monoclonal antibody with potent and broadly neutralizing activity
      against HIV-1. It targets the membrane-proximal external region (MPER) of the
      gp41 subunit of the envelope glycoprotein and interferes with the process of
      fusion between viral and host cell membranes. This study presents eight 2F5
      F(ab)' crystal structures in complex with various gp41 peptide epitopes. These
      structures reveal several key features of this antibody-antigen interaction. (1)
      Whenever free of contacts caused by crystal artifacts, the extended
      complementarity-determining region H3 loop is mobile; this is true for ligand
      free and epitope-bound forms. (2) The interaction between the antibody and the
      gp41 ELDKWA epitope core is absolutely critical, and there are also close and
      specific contacts with residues located N-terminal to the epitope core. (3)
      Residues located at the C-terminus of the gp41 ELDKWA core do not interact as
      tightly with the antibody. However, in the presence of a larger peptide
      containing the gp41 fusion peptide segment, these residues adopt a conformation
      consistent with the start of an alpha-helix. (4) At high sulfate concentrations,
      the electron density maps of 2F5 F(ab)'-peptide complexes contain a peak that may
      mark a binding site for phosphate groups of negatively charged lipid headgroups.
      The refined atomic-level details of 2F5 paratope-epitope interactions revealed
      here should contribute to a better understanding of the mechanism of 2F5-based
      virus neutralization, in general, and prove important for the design of potential
      vaccine candidates intended to elicit 2F5-like antibody production.

PMID- 18824006
TI  - Biochemical and structural characterization of an intramolecular interaction in
      FOXO3a and its binding with p53.
AB  - FOXO3a, a forkhead transcription factor and member of the forkhead box class O
      (FOXO) subfamily, has been shown to promote the translocation of p53 to the
      cytoplasm, thereby inducing the mitochondria-associated apoptotic pathway.
      However, the binding sites that mediate this interaction between FOXO3a and p53
      have not been identified. Here, we show that two regions within FOXO3a, the
      forkhead (FH) DNA binding domain and a conserved C-terminal transactivation
      domain (CR3), interact with the DNA binding domain of p53, with affinities in the
      low millimolar range and low micromolar range, respectively. Our data further
      suggest that within the FOXO3a molecule, the FH and CR3 domains engage in an
      intramolecular interaction with low micromolar affinity. Moreover, we used NMR to
      determine the solution structure of the FH domain. This enabled us to map the
      binding site for the CR3, which overlaps with the DNA binding site. We
      demonstrate that an intrinsically disordered linker between the FH and CR3
      domains is required for full p53 binding activity. We also show that p53 disrupts
      the intramolecular interaction between FH and CR3. These results provide evidence
      for interplay of the FH and CR3 domains in association with p53.

PMID- 18824007
TI  - Effect of increased dietary salinity on the reproductive status and energy intake
      of xeric and mesic populations of the spiny mouse, Acomys.
AB  - The possible role of increased dietary salinity as a proximate regulator of
      reproduction in xeric population of golden spiny mice (Acomys russatus) and mesic
      population of common spiny mice (A. cahirinus) was tested. In the wild, as the
      dry season progresses, evaporative water loss in the vegetation increases. This
      leads to increase in particle concentration of plant tissues. Thus, species
      consuming a plant diet are exposed to increased dietary salinity. Both male and
      female individuals of A. russatus were subjected to gradually increasing dietary
      salinity (0.9%, 2.5%, 3.5%, and 5%) while those of A. cahirinus only up to 3.5%
      for a total period of 8 and 6 weeks, respectively. Urine osmolarity showed a
      significant increase under 3.5% and 5% salinity in A. russatus and 2.5% and 3.5%
      in A. cahirinus. Testis mass and spermatogenesis were significantly reduced while
      uterine mass and vaginal estrus cycles were not affected in A. russatus. None of
      the parameters was significantly affected in A. cahirinus. Increase in salinity
      also significantly reduced body mass in A. russatus but not in A. cahirinus. Mass
      specific daily digestible energy intake was not significantly affected by
      increased salinity in both species. Recovery individuals regained body mass
      quickly and surpassed initial values after four weeks. However, testis mass and
      spermatogenesis did not show recovery. The results suggest that increase in
      dietary salinity could be used as a proximate signal to regulate reproduction in
      A. russatus by halting it in males, as the dry season progresses while such role
      in the mesic population of A. cahirinus is unlikely.

PMID- 18824008
TI  - Clustered DNA lesion sites as a source of mutations during human colorectal
      tumourigenesis.
AB  - The role of gene mutations in tumourigenesis is well understood, however, the
      mechanism(s) by which they arise are less clear. Indeed, the common assumption
      that tumourigenic mutations are the result of DNA replication errors is
      apparently contradicted by the very low division frequency of the cells from
      which tumours are thought to arise (i.e. deep stem cells). As a potential
      solution to this paradox, we tested a model whereby clustered DNA lesion sites
      (CLS) (where several lesions occur within a few base pairs of each other on
      opposing strands) could give rise to mutations in quiescent cells. We used
      statistical analyses to search for sets of dinucleotide sequences (designated
      target sequences) that are present at and in close proximity to mutation sites in
      four genes associated with human colorectal tumourigenesis (adenomatosis
      polyposis coli (APC), v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog
      (KRAS), phosphoinositide-3-kinase, catalytic, alpha polypeptide (PIK3CA), and
      tumour protein p53 (TP53)). The dinucleotides CG, AC-GT, TG, and GC were
      identified as target sequences in at least three of the genes analysed.
      Consistent with their designation as target sequences, these dinucleotides have
      all been identified as high probability sites of oxidative damage formation in in
      vitro studies. Our results strongly suggest a statistical association between the
      presence of multiple, clustered target sequences and mutational events. We
      propose that CLS are a major source of mutations during human tumourigenesis.

PMID- 18824009
TI  - Regulation of cytochrome P4501A1 expression by hyperoxia in human lung cell
      lines: Implications for hyperoxic lung injury.
AB  - Supplemental oxygen, used to treat pulmonary insufficiency in newborns,
      contributes to the development of bronchopulmonary dysplasia (BPD). Cytochrome
      P4501A enzymes are induced by hyperoxia in animal models, but their role in human
      systems is unknown. Here we investigated the molecular mechanisms of induction of
      CYP1A1 by hyperoxia in human lung cell lines. Three human lung cell lines were
      exposed to hyperoxia (95% O2) for 0-72 h, and CYP1A1 activities, apoprotein
      contents, and mRNA levels were determined. Hyperoxia significantly induced CYP1A1
      activity and protein contents (2-4 fold), and mRNA levels (30-40 fold) over
      control in each cell line. Transfection of a CYP1A1 promoter/luciferase reporter
      construct, followed by hyperoxia (4-72 h), showed marked (2-6 fold) induction of
      luciferase expression. EMSA and siRNA experiments strongly suggest that the Ah
      receptor (AHR) is involved in the hyperoxic induction of CYP1A1. MTT reduction
      assays showed attenuation of cell injury with the CYP1A1 inducer beta
      naphthoflavone (BNF). Our results strongly suggest that hyperoxia
      transcriptionally activates CYP1A1 expression in human lung cell lines by AHR
      dependent mechanisms, and that CYP1A1 induction is associated with decreased
      toxicity. This novel finding of induction of CYP1A1 in the absence of exogenous
      AHR ligands could lead to novel interventions in the treatment of BPD.

PMID- 18824010
TI  - Cytochrome P450-mediated activation of the fragrance compound geraniol forms
      potent contact allergens.
AB  - Contact sensitization is caused by low molecular weight compounds which penetrate
      the skin and bind to protein. In many cases, these compounds are activated to
      reactive species, either by autoxidation on exposure to air or by metabolic
      activation in the skin. Geraniol, a widely used fragrance chemical, is considered
      to be a weak allergen, although its chemical structure does not indicate it to be
      a contact sensitizer. We have shown that geraniol autoxidizes and forms
      allergenic oxidation products. In the literature, it is suggested but not shown
      that geraniol could be metabolically activated to geranial. Previously, a skin
      like CYP cocktail consisting of cutaneous CYP isoenzymes, was developed as a
      model system to study cutaneous metabolism. In the present study, we used this
      system to investigate CYP-mediated activation of geraniol. In incubations with
      the skin-like CYP cocktail, geranial, neral, 2,3-epoxygeraniol, 6,7-epoxygeraniol
      and 6,7-epoxygeranial were identified. Geranial was the main metabolite formed
      followed by 6,7-epoxygeraniol. The allergenic activities of the identified
      metabolites were determined in the murine local lymph node assay (LLNA).
      Geranial, neral and 6,7-epoxygeraniol were shown to be moderate sensitizers, and
      6,7-epoxygeranial a strong sensitizer. Of the isoenzymes studied, CYP2B6, CYP1A1
      and CYP3A5 showed high activities. It is likely that CYP1A1 and CYP3A5 are mainly
      responsible for the metabolic activation of geraniol in the skin, as they are
      expressed constitutively at significantly higher levels than CYP2B6. Thus,
      geraniol is activated through both autoxidation and metabolism. The allergens
      geranial and neral are formed via both oxidation mechanisms, thereby playing a
      large role in the sensitization to geraniol.

PMID- 18824011
TI  - N-type and P/Q-type calcium channels regulate differentially the release of
      noradrenaline, ATP and beta-NAD in blood vessels.
AB  - Using HPLC techniques we evaluated the electrical field stimulation-evoked
      overflow of noradrenaline (NA), adenosine 5'-triphosphate (ATP), and beta
      nicotinamide adenine dinucleotide (beta-NAD) in the presence of low nanomolar
      concentrations of omega-conotoxin GVIA or omega-agatoxin IVA in the canine
      mesenteric arteries and veins. omega-conotoxin GVIA abolished the evoked overflow
      of NA and beta-NAD in artery and vein, whereas the evoked overflow of ATP
      remained unchanged in the presence of omega-conotoxin GVIA. omega-agatoxin IVA
      significantly reduced the evoked overflow of ATP and beta-NAD. The overflow of NA
      remained largely unaffected by omega-agatoxin IVA, except at 16Hz in the vein
      where the overflow of NA was reduced by about 50%. Artery and vein exhibited
      similar expression levels of the alpha(1B) (CaV2.2, N-type) subunit, whereas the
      vein showed greater levels of the alpha(1A) (CaV2.1, P/Q-type) subunit than
      artery. Therefore, there are at least two release sites for NA, beta-NAD and ATP
      in the canine mesenteric artery and vein: an N-type-associated site releasing
      primarily NA, beta-NAD and some ATP, and a P/Q-type-associated site releasing
      ATP, beta-NAD and some NA. The N-type-mediated mechanisms are equally expressed
      in artery and vein, whereas the P/Q-type-mediated mechanisms are more pronounced
      in the vein and may ensure additional neurotransmitter release at higher levels
      of neural activity. In artery, beta-NAD caused a dual effect consisting of
      vasodilatation or vasoconstriction depending on concentrations, whereas vein
      responded with vasodilatation only. In contrast, ATP caused vasoconstriction in
      both vessels. beta-NAD and ATP may mediate disparate functions in the canine
      mesenteric resistive and capacitative circulations.

PMID- 18824012
TI  - The GABA(B) receptor agonist, baclofen, and the positive allosteric modulator,
      CGP7930, inhibit visceral pain-related responses to colorectal distension in
      rats.
AB  - Activation of GABA(B) receptors by the selective agonist baclofen produces anti
      nociceptive effects in animal models of somatic pain. The aim of the present
      study was to evaluate the effect of baclofen and the GABA(B) receptor positive
      allosteric modulator CGP7930 on pseudo-affective responses to colorectal
      distension in rats. Female Sprague-Dawley rats were subjected to repeated,
      noxious colorectal distension (CRD) (12 distensions at 80 mmHg, for 30 s with 5
      min intervals). The visceromotor response (VMR) and cardiovascular responses
      (mean arterial blood pressure (ABP) and heart rate (HR)) to CRD were monitored in
      conscious, telemetrized animals. Baclofen (0.3-3 micromol/kg, i.v.) reduced the
      VMR to CRD dose-dependently, reaching a 61% maximal inhibition (p < 0.001). The
      highest doses of baclofen attenuated CRD-evoked increases in ABP by 17% (p >
      0.05) and reduced the change in HR by 48% (p < 0.01). CGP7930 (3-30 micromol/kg,
      i.v.) reduced the VMR to CRD in a dose-dependent fashion with a maximal
      inhibition of 31% (p < 0.05). The highest dose of CGP7930 also attenuated the
      increase in ABP by 18% (p > 0.05) and inhibited the increase in HR by 24% (p <
      0.05) associated with CRD. Neither baclofen nor CGP7930 affected colorectal
      compliance. The results suggest that activation of GABA(B) receptors produces
      anti-nociceptive effects in a rat model of mechanically induced visceral pain.
      While CGP7930 was less efficacious than baclofen overall, positive allosteric
      modulation of GABA(B) receptors may represent a valid approach in the treatment
      of visceral pain conditions, with the possibility of an improved safety profile
      compared to full agonism.

PMID- 18824013
TI  - Assessment of metalloproteinase inhibitors clodronate and doxycycline in the
      neutralization of hemorrhage and coagulopathy induced by Bothrops asper snake
      venom.
AB  - Snake venom metalloproteinases (SVMPs) play a prominent role in the local and
      systemic manifestations of viperid snakebite envenomations. Thus, the possibility
      of using metalloproteinase inhibitors in the treatment of these envenomations is
      a promising therapeutic alternative. This study assessed the ability of two
      metalloproteinase inhibitors, the biphosphonate clodronate and the tetracycline
      doxycycline, to inhibit proteolytic, hemorrhagic, coagulant and defibrinogenating
      effects of Bothrops asper venom. Both compounds were able to inhibit these
      activities, at concentrations in the mM range, when incubated with venom prior to
      testing. However, when inhibition of hemorrhage was assessed in assays involving
      independent injection of venom and drug, inhibition was poor, even when these
      compounds were injected immediately after envenomation. These findings support
      the concept that the effectiveness of compounds, such as clodronate and
      doxycycline, whose inhibitory action on SVMPs is based on zinc chelation alone,
      is limited, and stress the view that more specific molecules are required for an
      effective inhibition of SVMPs in vivo.

PMID- 18824014
TI  - The electroretinogram (ERG) of a diurnal cone-rich laboratory rodent, the Nile
      grass rat (Arvicanthis niloticus).
AB  - The most widespread models to study blindness, rats and mice, have retinas
      containing less than 3% cones. The diurnal rodent Arvicanthis niloticus retina
      has around 35% cones. Using ERG recordings, we studied retina function in this
      species. Several features differed from that reported in rats and mice: (a)
      fivefold larger photopic a-wave amplitudes; (b) photopic hill effect in Nile
      grass rats only; and (c) flicker amplitude plateau between 5 to 35 Hz with fusion
      beyond 60 Hz in Nile grass rats only. We conclude that A. niloticus might
      complement rats and mice for studying retinal function and pathologies involving
      cones.

PMID- 18824015
TI  - Contextual effects on decision templates for parafoveal orientation
      identification.
AB  - When a peripherally viewed stimulus is presented with flankers, observers' acuity
      for shape generally decreases. We wondered whether a change in the locus of
      information accrual accompanied these performance deficits and employed
      psychophysical reverse correlation to find out. Surrounding the target (a near
      vertical Gabor patch) with a vertical grating caused a slight elongation and a
      rotation in the decision templates for orientation identification. We also found
      that the contrast required to maintain criterion performance in this condition
      was actually lower than it was in a target-alone condition. However, this
      facilitation decreased with practice, due to perceptual learning in the target
      alone condition. Unlike a continuous surround, isolated flanks elevated contrast
      thresholds, but decision templates were similar with both of these contexts. The
      rotation of decision templates (off-orientation looking) suggests that
      performance is limited by additive internal noise. We speculate that this noise
      can be reduced when the target is easily segregated from its surround.

PMID- 18824016
TI  - Perceived spatial displacement of motion-defined contours in peripheral vision.
AB  - The perceived displacement of motion-defined contours in peripheral vision was
      examined in four experiments. In Experiment 1, in line with Ramachandran and
      Anstis' finding [Ramachandran, V. S., & Anstis, S. M. (1990). Illusory
      displacement of equiluminous kinetic edges. Perception, 19, 611-616], the border
      between a field of drifting dots and a static dot pattern was apparently
      displaced in the same direction as the movement of the dots. When a uniform dark
      area was substituted for the static dots, a similar displacement was found, but
      this was smaller and statistically insignificant. In Experiment 2, the border
      between two fields of dots moving in opposite directions was displaced in the
      direction of motion of the dots in the more eccentric field, so that the location
      of a boundary defined by a diverging pattern is perceived as more eccentric, and
      that defined by a converging as less eccentric. Two explanations for this effect
      (that the displacement reflects a greater weight given to the more eccentric
      motion, or that the region containing stronger centripetal motion components
      expands perceptually into that containing centrifugal motion) were tested in
      Experiment 3, by varying the velocity of the more eccentric region. The results
      favoured the explanation based on the expansion of an area in centripetal motion.
      Experiment 4 showed that the difference in perceived location was unlikely to be
      due to differences in the discriminability of contours in diverging and
      converging patterns, and confirmed that this effect is due to a difference
      between centripetal and centrifugal motion rather than motion components in other
      directions. Our result provides new evidence for a bias towards centripetal
      motion in human vision, and suggests that the direction of motion-induced
      displacement of edges is not always in the direction of an adjacent moving
      pattern.

PMID- 18824017
TI  - Reproductive success and mate choice in Long-Evans rats.
AB  - In the present study, mating behavior was observed in female rats that were given
      the opportunity to mate with two male rats simultaneously. Eleven sexually naive,
      naturally cycling rats were assigned to one pair of sexually experienced
      cohabitating male rats. Each female rat was mated during proestrous with her
      assigned pair of males. Eight females successfully became pregnant and gave birth
      to healthy pups (approximately 9 pups/litter). After the offspring were weaned,
      paternity of each pup was determined using microsatellite DNA markers. Based on
      this analysis, it was determined that one male in each pair sired the majority of
      the pups in the litter. No male sexual behaviors or characteristics distinguished
      male rats that sired the majority of pups from those that sired few or none of
      the pups. Furthermore, neither female mate preference nor measures of paced
      mating behavior differed between male rats that had a reproductive advantage from
      those that did not. Finally, ejaculation order also failed to predict
      reproductive success of the male rats. Together, these results suggest that
      reproductive success of some male rats may not depend on specific mating
      behaviors, but rather their success may depend on physiological or genetic traits
      that make them unique.

PMID- 18824018
TI  - Effects of repeated yohimbine on the extinction and reinstatement of cocaine
      seeking.
AB  - Acute exposure to the pharmacological stressor yohimbine (YOH) reinstates drug
      seeking in rats. The present experiments investigated whether repeated exposure
      to YOH during extinction training affects the time-course of extinction and the
      magnitude of subsequent YOH- or footshock-induced reinstatement of cocaine
      seeking. Rats trained to self-administer cocaine were given five days of
      extinction training, during which they were injected with YOH (1.25 mg/kg, i.p.)
      either before or after daily extinction sessions. Following additional extinction
      training in the absence of YOH, animals were tested for reinstatement to a YOH
      (1.25 mg/kg, i.p.) or footshock (20 min, intermittent, 0.9 mA per 0.5 s shock)
      challenge. Animals injected with YOH before daily extinction sessions showed an
      attenuated rate of extinction, relative to control animals. Following additional
      extinction training in the absence of YOH treatment, these same animals showed a
      marked attenuation of YOH-induced reinstatement of cocaine seeking. YOH treatment
      during extinction did not, however, affect the magnitude of reinstatement induced
      by footshock. These findings demonstrate that repeated exposure to a stressor
      during extinction training can modulate the processes governing extinction
      learning and the subsequent reinstatement of drug seeking induced by that
      stressor.

PMID- 18824019
TI  - A single administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin that produces
      reduced food and water intake induces long-lasting expression of corticotropin
      releasing factor, arginine vasopressin, and proopiomelanocortin in rat brain.
AB  - The mechanism by which a single administration of 2,3,7,8-tetrachlorodibenzo-p
      dioxin (TCDD) reduces food and water intake is unclear. We examined whether such
      a food and water intake-reducing single administration of TCDD induced changes in
      corticotropin-releasing factor (CRF), arginine vasopressin (AVP), and
      proopiomelanocortin (POMC) expression in rat brain. To observe time-dependent
      changes in these neuropeptides, male Sprague-Dawley rats were given TCDD (50
      microg/kg) and terminated 1, 2, 4, or 7 days later. In addition, to observe dose
      dependent changes in feeding and neuropeptides, rats were also given a range of
      TCDD doses (12.5, 25, or 50 microg/kg) and terminated 14 days later. TCDD
      suppressed food and water intake over 14 days in a dose-dependent manner. TCDD
      treatment also increased CRF and POMC mRNA levels in the hypothalamic
      paraventricular nucleus (PVN) and arcuate nucleus, respectively, in a dose- and
      time-dependent manner. These increases were related to decreased food intake
      following TCDD administration. TCDD treatment increased AVP and CRF mRNA levels
      in the PVN, and these increases were related to decreased water intake.
      Interestingly, the increases in CRF, AVP and POMC expression were observed 7 to
      14 days after TCDD administration. These results suggest that a single
      administration of TCDD induced long-lasting increases in CRF, AVP, and POMC mRNA
      levels in the hypothalamus and that these changes are related to reduced food and
      water intake 7 to 14 days after TCDD administration.

PMID- 18824020
TI  - WITHDRAWN: Nanomaterials Chemistry: Recent Developments and New Directions.
AB  - The Publisher regrets that this article is an accidental duplication of an
      article that has already been published in Int. J. Biol. Macromol,
      doi:10.1016/j.ijbiomac.2008.07.012. The duplicate article has therefore been
      withdrawn.

PMID- 18824021
TI  - Assessing aversive emotional states through the heart in mice: implications for
      cardiovascular dysregulation in affective disorders.
AB  - Beat-to-beat fluctuations of heart rate (HR) convey information of the brain
      state with the cardiac time series reflecting the flow of efferent nerve traffic
      of the autonomic nervous system. Instantaneous HR was studied in mice during
      exposure to novelty and the expression of fear conditioned to an auditory cue as
      affective challenge to characterize baseline dynamics and conditioned adjustments
      to learned fear. These studies included pharmacological and genetic interventions
      of brain systems implicated in aversive emotional states, the corticotropin
      releasing factor (CRF) system and the serotonin (5-HT)1A receptor. Non-linear
      analyses of neuroautonomic cardiac control provide for functionally adequate
      measures of dynamical properties. Both CRF1 and 5-HT1A receptor agonists elicited
      profound sympatho-vagal antagonism with pathological HR dynamics indicative of
      central autonomic dysregulation via mechanisms resulting in impaired fear
      adjustment. Non-linear measures provide for a qualitative assessment of dynamical
      features with regard to physiological or pathological state, are crucial for the
      translation of results from mouse to man, and may improve our understanding of
      brain-heart interactions for autonomic dysregulation in affective disorders.

PMID- 18824023
TI  - Expression profiles of cloned channel catfish (Ictalurus punctatus) lymphoid cell
      lines and mixed lymphocyte cultures.
AB  - Clonal channel catfish lymphoid cell lines and mixed lymphocyte cultures (MLCs)
      have proven extremely useful in examining immune responses at the cellular and
      molecular levels. To date clonal catfish cell lines and MLCs have been
      biologically and phenotypically characterized using a variety of techniques
      including reverse transcription polymerase chain reaction (RT-PCR), as well as
      Northern and Southern blotting. To expand the molecular characterization of these
      cultures, microarray analysis was employed. Clonal B (3B11), macrophage (42TA),
      and cytotoxic T cell (TS32.15 and TS32.17) lines and MLCs were examined using a
      cDNA array containing approximately 2500 probes derived from EST libraries
      prepared from the 42TA macrophage cell line, a MLC, and 5-14-day-old catfish fry.
      Analysis showed that each cell line displayed a unique RNA expression profile
      that included a variety of immune-related genes. Pearson correlation analysis
      indicated that one cytotoxic T cell line (TS32.15) clustered with the MLC,
      whereas a second cytotoxic T cell line (TS32.17) was more closely associated with
      a second cluster containing B cells and macrophages. This study illustrates the
      utility of microarray analyses in profiling RNA expression patterns in catfish
      lymphoid cell lines and will serve as a platform for examining catfish immune
      responses following virus infection or poly [I:C] treatment.

PMID- 18824022
TI  - Effects of naltrexone on cortisol levels in heavy drinkers.
AB  - The primary objectives of this study were to: (a) examine the neuroendocrine
      effects of naltrexone vs. placebo by comparing serum cortisol levels; and (b)
      test the biobehavioral correlates of naltrexone-induced changes in cortisol. Non
      treatment seeking heavy drinkers (n=37) completed two intravenous alcohol
      administrations, one after naltrexone (50 mg) and one after placebo. Cortisol
      levels were measured at baseline and after alcohol intake (BrAC=0.06 g/dl) on
      both sessions, as were subjective responses to alcohol. Analyses revealed that
      naltrexone significantly raised overall cortisol levels compared to placebo.
      Cortisol levels decreased during alcohol administration and a stronger decrease
      was observed in the naltrexone condition. Cortisol levels were, in turn,
      inversely related to some of alcohol's the reinforcing effects (i.e., alcohol
      'high,' vigor) and positively associated with some of its unpleasant effects
      (i.e., sedation and subjective intoxication). These results suggest that
      naltrexone alters cortisol levels in heavy drinkers and that its effects on
      subjective responses to alcohol may be related, in part, to naltrexone's ability
      to activate the HPA-axis.

PMID- 18824024
TI  - Synaptic effects of low molecular weight components from Chilean Black Widow
      spider venom.
AB  - alpha-Latrotoxin is the principal component of the venom from the euroasiatic
      Black Widow spider and has been studied for its pharmacological use as a synaptic
      modulator. Interestingly, smaller molecular weight fractions have been found to
      be associated with this toxin, but their cellular actions have not been studied
      in detail. The venom from the Chilean Black Widow spider (Latrodectus mactans)
      does not produce alpha-latrotoxin, however it does contain several small
      polypeptides. We have recently demonstrated cellular effects of these peptides at
      the synaptic level using whole-cell patch clamp techniques. Purified venom from
      the glands of L. mactans was studied in 12 DIV rat hippocampal neuronal cultures.
      Venom at a concentration of 10nM was able to decrease neuronal conductance
      thereby increasing membrane resistance. This effect on the passive properties of
      the neurons induced a change in action potential kinetics simulating the action
      of classic potassium channel blockers. These changes produced an increase in
      spontaneous synaptic activity in rat hippocampal cultures in the presence of the
      venom in a concentration- and time-dependent manner. These results indicate that
      venom from Chilean spider L. mactans is capable of increasing cell membrane
      resistance, prolonging the action potential and generating an increase in
      synaptic activity demonstrating an interesting pharmacological effect of these
      low molecular weight fragments.

PMID- 18824026
TI  - Does the physical disector method provide an accurate estimation of sensory
      neuron number in rat dorsal root ganglia?
AB  - The physical disector is a method of choice for estimating unbiased neuron
      numbers; nevertheless, calibration is needed to evaluate each counting method.
      The validity of this method can be assessed by comparing the estimated cell
      number with the true number determined by a direct counting method in serial
      sections. We reconstructed a 1/5 of rat lumbar dorsal root ganglia taken from two
      experimental conditions. From each ganglion, images of 200 adjacent semi-thin
      sections were used to reconstruct a volumetric dataset (stack of voxels). On
      these stacks the number of sensory neurons was estimated and counted respectively
      by physical disector and direct counting methods. Also, using the coordinates of
      nuclei from the direct counting, we simulate, by a Matlab program, disector pairs
      separated by increasing distances in a ganglion model. The comparison between the
      results of these approaches clearly demonstrates that the physical disector
      method provides a valid and reliable estimate of the number of sensory neurons
      only when the distance between the consecutive disector pairs is 60 microm or
      smaller. In these conditions the size of error between the results of physical
      disector and direct counting does not exceed 6%. In contrast when the distance
      between two pairs is larger than 60 microm (70-200 microm) the size of error
      increases rapidly to 27%. We conclude that the physical dissector method provides
      a reliable estimate of the number of rat sensory neurons only when the separating
      distance between the consecutive dissector pairs is no larger than 60 microm.

PMID- 18824025
TI  - A rat head holder for simultaneous scanning of two rats in small animal PET
      scanners: design, construction, feasibility testing and kinetic validation.
AB  - To reduce imaging costs, we designed a head holder for scanning two rats
      simultaneously in small animal PET scanners. Our goals were (i) to maintain high
      sensitivity and (ii) to minimize repositioning error between scans. METHODS: A
      semi-stereotaxic dual rat head holder was designed and constructed for dual rat
      scanning in our IndyPET-II scanner and the commercial microPET P4. It was also
      used for single rat scanning in a small-bore, high-resolution animal scanner
      ("ISAP"). Positional repeatability was validated via multiple [11C]Raclopride
      scans of a single rat on different days. Accuracy of repositioning was determined
      by visual comparison of images, and by metrics derived through image alignment.
      Kinetic validation was assessed via analysis of [18F]Fluorodeoxyglucose
      ([18F]FDG) dynamic PET studies of six rats. Each rat was scanned twice: once
      individually, with brain positioned at the center of field of view (CFOV), and
      once with a partner, with brain away from CFOV. Both rats were injected with FDG
      during each dual rat session. Patlak uptake constants (Ki) were calculated from
      whole brain images. Effects of attenuation and scatter correction on single
      versus dual scan images were explored. RESULTS: Image comparison and alignment
      metrics indicated excellent repositioning of rats. Scaled time-activity-curves
      from single and dual rat scans were indistinguishable. Average single and dual
      scan Ki values differed by only 6.3+/-7.5%. CONCLUSION: Dual rat scanning in a
      semi-stereotaxic holder is practical for economical small animal scanning and
      does not compromise kinetic accuracy of [18F]FDG dynamic scan data.

PMID- 18824027
TI  - Characterisation of two antibodies to oligomeric Abeta and their use in ELISAs on
      human brain tissue homogenates.
AB  - Oligomeric forms of Abeta are believed to be the major toxic species of this
      peptide in Alzheimer's disease (AD). Although the characterisation of oligomer
      specific antibodies has been reported, these have not been successfully
      incorporated into an enzyme-linked immunosorbent assay (ELISA), and measurement
      of the levels of oligomeric Abeta in brain tissue has remained problematic. We
      have examined the specificity of two monoclonal antibodies, 7 A1a and 1G5, for
      synthetic oligomers of Abeta(1-42) and for oligomeric Abeta(1-42) in human brain
      homogenates, and the utility of these two antibodies for measuring oligomeric
      Abeta(1-42) by sandwich ELISA. Both antibodies were found to recognise a range of
      synthetic oligomers of Abeta(1-42) but to cross-react in Western blots with a 34
      kDa protein, shown by two-dimensional gel electrophoresis and mass spectrometry
      to be tropomyosin. However, by using 7A1a and 1 G5 in combination with an Abeta(1
      42) capture antibody, we were able specifically to detect and to measure the
      levels of oligomeric Abeta(1-42) in brain homogenates by ELISA. The development
      of a simple ELISA for measurement of oligomeric Abeta should facilitate further
      studies of the role of oligomeric species of Abeta in AD.

PMID- 18824028
TI  - TOXI-SIM-A simulation tool for the analysis of mitochondrial and plasma membrane
      potentials.
AB  - Changes in the electrochemical gradients across biological membranes are
      excellent indicators of pathophysiological processes, drug action, or drug
      toxicity. Our previous studies have utilized the potentiometric probe
      tetramethylrhodamine methyl ester (TMRM) to characterize changes in mitochondrial
      function by monitoring alterations in the mitochondrial membrane potential
      (Deltapsi(m)) over time during glutamate excitotoxicity. However, fluorescently
      charged dyes such as TMRM respond to changes in both Deltapsi(m) and the plasma
      membrane (Deltapsi(p)) potentials making whole cell fluorescence data difficult
      to interpret. Here we have implemented a mathematical model that exploits the
      Nernstian behaviour of TMRM and uses automated Newton based root-finding fitting
      (TOXI-SIM) to model changes in TMRM fluorescence from multiple cells
      simultaneously, providing output on changes in Deltapsi(m) and Deltapsi(p) over
      time. Based on Ca(2+) responses, TOXI-SIM allows for an accurate modelling of
      TMRM traces for different injury paradigms (necrosis, apoptosis, tolerance). TOXI
      SIM is provided as a user friendly public web service for trace analysis, with an
      additional online data base provided for the storage and retrieval of
      experimental traces (http://systemsbiology.rcsi.ie/tmrm/index.html).

PMID- 18824029
TI  - Measuring early pre-symptomatic changes in locomotion of SOD1-G93A rats--a rodent
      model of amyotrophic lateral sclerosis.
AB  - A locomotion analysis system for laboratory rats is presented. The system
      produces locomotion parameters (LPs) in 4 different domains: force, space, time
      and frequency. Video images of the walking rats are used to associate the system
      signals with individual limbs. Numerous LPs can be derived for every test run
      when the rat walks through the system on the way to sweets and a personal toy
      placed at the exit. This manuscript demonstrates that in order to differentiate
      SOD1-G93A mutant rat, a model of amyotrophic lateral sclerosis (ALS), from a
      Sprague Dawley (SD) control rat at a pre-symptomatic stage, one has only to use 8
      key parameters. These 8 parameters are the bio-markers of ALS. The spline-based
      transformed values of these parameters are used as explanatory variables of a
      logistic regression model. This model predicts the probability that the examined
      rat belongs to the SOD1-G93A group. The model differentiates faultlessly between
      the SOD1 and control groups from the very first time the rats walked through the
      system at 51 days old. This system provides a new paradigm for ALS diagnosis, and
      it can have a significant impact on the development of new therapeutic procedures
      for ALS. The methodology presented in this manuscript can further address the
      development and validation of therapeutic procedures for other neurological
      diseases that affect locomotion.

PMID- 18824030
TI  - Psychiatric vulnerability: suggestions from animal models and role of
      neurotrophins.
AB  - Nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) are well
      studied neurotrophins involved in the neurogenesis, differentiation, growth and
      maintenance of selected peripheral and central populations of neuronal cells
      during development and at adulthood. Neurotrophins, in concert to hypothalamic
      pituitary-adrenal (HPA) axis, play a key role in modulating brain plasticity and
      behavioral coping, especially during ontogenetic critical periods, when
      developing brain is particularly sensitive to external stimulations. Indeed,
      early life events, such psychophysical stress, affect NGF and BDNF levels, and
      induce dysregulation of the HPA axis. Thus, early life experiences can affect
      brain development, contributing to shape interindividual differences in
      vulnerability to stress or psychiatric disorders. At adulthood, intermale
      aggressive interactions in mice, representing a psychosocial stressful condition,
      has been shown to markedly alter NGF and BDNF levels both in plasma as well as in
      selected brain areas, including the hypothalamus and hippocampus. These results
      have been extended to humans, showing that blood NGF levels are enhanced in
      psychological contexts mainly associated to anxiety and fear, such as first
      skydiving experience. Recent studies indicate a role for neurotrophins also in
      vulnerability and resilience to stress-related neuropsychiatric disorders.
      Overall, these findings suggest a role of neurotrophins as factors mediating both
      short- and long-term experience effects on brain structure and function.

PMID- 18824031
TI  - Dose-dependent food allergy induction against ovalbumin under acid-suppression: a
      murine food allergy model.
AB  - BACKGROUND: Animal models are essential for analyzing the allergenic potential of
      food proteins and for investigating mechanisms underlying food allergy. Based on
      previous studies revealing acid-suppression medication as risk factor for food
      allergy induction, we aimed to establish a mouse model mimicking the natural
      route of sensitization in patients. METHODS: The effect of acid-suppressing
      medication on murine gastric pH was assessed by intragastric pH measurements
      after two injections of a proton pump inhibitor (PPI). To investigate dose
      dependency, mice were fed different concentrations of ovalbumin (OVA; 0.2, 0.5,
      1.0, 2.5 or 5.0mg) either with or without anti-ulcer medication. Additionally,
      different routes of exposure (i.p. vs. oral) were compared in a second
      immunization experiment. Sera were screened for OVA-specific antibody titers
      (IgG1, IgG2a and IgE) in ELISA and RBL assay. Clinical reactivity was evaluated
      by measuring rectal temperature after oral challenge and by type I skin tests.
      RESULTS: Two intravenous injections of PPI significantly elevated the gastric pH
      from 2.97 to 5.3. Only oral immunization with 0.2mg OVA under anti-acid
      medication rendered elevated IgG1, IgG2a and IgE titers compared to all other
      concentrations. Protein feeding alone altered antibody titers only marginally.
      Even though also i.p. immunizations induced high levels of specific IgE, only
      oral immunizations under anti-acids induced anaphylactic reactions evidenced by a
      significant decrease of body temperature. CONCLUSION: Only low-dosage ovalbumin
      feedings under anti-acid medication resulted in IgE mediated food allergy. Based
      on this knowledge we have established a suitable food allergy model for further
      investigations of food adverse reactions.

PMID- 18824032
TI  - The protective effect of neuronal nitric oxide synthase (nNOS) against alcohol
      toxicity depends upon the NO-cGMP-PKG pathway and NF-kappaB.
AB  - Fetal alcohol syndrome (FAS) stems from maternal alcohol abuse during pregnancy
      and is an important cause of mental retardation and hyperactivity in children. In
      the developing brain, alcohol can kill neurons, leading to microencephaly.
      However, due to their genetic makeup, some individuals are less vulnerable than
      others to alcohol's neurotoxic effects. Animal studies have demonstrated that one
      particular gene, neuronal nitric oxide synthase (nNOS), protects developing
      neurons in vivo against alcohol-induced death. We utilized pharmacologic
      techniques to demonstrate that nNOS protects neurons against alcohol toxicity by
      activating the NO-cGMP-PKG signaling pathway. Cerebellar granule cell cultures
      derived from mice carrying a null mutation for nNOS (nNOS-/- mice) were
      substantially more vulnerable than cultures from wild-type mice to alcohol
      induced cell death. However, activation of the pathway at sites downstream of
      nNOS protected the cultures against alcohol toxicity. Conversely, blockade of the
      pathway rendered wild-type cultures vulnerable to alcohol-induced death. We
      further identified NF-kappaB as the downstream effector through which nNOS and
      the NO-cGMP-PKG pathway signal their neuroprotective effects. Tumor necrosis
      factor-alpha (TNF-alpha), which activates NF-kappaB, ameliorated alcohol-induced
      cell death in nNOS-/- and wild-type cultures, while an NF-kappaB inhibitor (NFi)
      blocked the protective effects of TNF-alpha and worsened alcohol-induced cell
      death. Furthermore, NFi blocked the protective effects of NO-cGMP-PKG pathway
      activators, demonstrating that NF-kappaB is downstream of the NO-cGMP-PKG
      pathway. As wild-type neurons matured in culture, they became resistant to
      alcohol toxicity. However, this maturation-dependent alcohol resistance did not
      occur in nNOS-/- mice and could be reversed in wild-type mice with NFi,
      demonstrating that nitric oxide and NF-kappaB are crucial for the development of
      alcohol resistance with age. Thus, nNOS protects developing neurons against
      alcohol toxicity by activating the NO-cGMP-PKG-NF-kappaB pathway and is crucial
      for the acquisition of maturation-dependent alcohol resistance.

PMID- 18824033
TI  - Biochemical and structural characterization of RHDV capsid protein variants
      produced in Pichia pastoris: advantages for immunization strategies and vaccine
      implementation.
AB  - Rabbit hemorrhagic disease virus (RHDV) VP60 capsid protein was recently
      expressed at approximately 1.5 gL(-1) associated with the disruption pellet of
      Pichia pastoris, thus requiring an additional process of extraction by
      solubilization. Consequently, the expression of a soluble variant of VP60 was
      undertaken in order to attain an easier approach for vaccine production. The VP60
      gene was cloned without secretion signal under the transcriptional control of the
      AOX1 yeast promoter. The antigen obtained was intracellular and soluble at
      approximately 480 mg L(-1). Its characterization by size-exclusion HPLC,
      ultracentrifugation, and electron microscopy, showed the presence of high
      molecular weight structures similar in mass, size and buoyant density to native
      RHDV. The antigenic profile was similar to that from authentic virions as
      determined with monoclonal antibodies directed against RHDV conformational
      epitopes. These analyses, conducted on VP60 obtained insoluble in P. pastoris
      revealed the formation of protein aggregates rather than the presence of ordered
      multimeric structures. An immunization trial was conducted in which the soluble
      VP60 was employed by subcutaneous (s.c.) injection either purified by a single
      chromatographic step or contained within raw disruption supernatant, emulsified
      in Montanide 888. The insoluble variant was administered as a yeast extract
      powder by oral and s.c. routes. The earliest IgG response, titers and persistence
      of antibodies were studied by competition ELISA and hemagglutination inhibition
      (HI) assays. All rabbits immunized with the yeast-derived antigens developed a
      strong RHDV-specific response (including the "RHDVa" subtype) that lasted over
      one year after the primary immunization. Early HI titers up to 1/40 960 were
      generated. The immune response was similar to that induced by VP60 from Sf9 cells
      and superior to the response elicited with inactivated RHDV. Overall it was found
      that the soluble VP60 multimers, safely and easily produced in P. pastoris, are a
      valuable candidate for the rational implementation of a low-cost, scalable
      subunit vaccine against RHDV.

PMID- 18824034
TI  - Recent insights into hepatic lipid metabolism in non-alcoholic fatty liver
      disease (NAFLD).
AB  - Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease
      in Western countries and is considered the hepatic manifestation of metabolic
      syndrome. The hallmark of NAFLD is hepatic neutral lipid accumulation, mainly
      triacylglycerol, in the absence of significant ethanol consumption, viral
      infection or other specific etiologies. Hepatic lipid accumulation results from
      an imbalance between lipid availability (from circulating lipid uptake or de novo
      lipogenesis) and lipid disposal (via free fatty acid oxidation or triglyceride
      rich lipoprotein secretion) and eventually triggers lipoperoxidative stress and
      hepatic injury. Each of these steps is altered in NAFLD, although to a different
      extent. Regulation of these pathways is complex and involves nuclear receptors,
      membrane transport proteins and cellular enzymes. We will review available data
      on different steps of hepatic lipid metabolism in NAFLD and recent advances in
      understanding molecular mechanisms underlying hepatic fat accumulation in these
      subjects.

PMID- 18824035
TI  - Dynamic behavioural changes in the Spontaneously Hyperactive Rat: 3. Control by
      reinforcer rate changes and predictability.
AB  - Variable intervals are widely believed to produce steady rates of responding.
      However, based on the calming effect of unpredictability in attention deficit
      hyperactivity disorder (ADHD) we hypothesised that an animal model of this
      disorder, the Spontaneously Hyperactive (or Hypertensive) Rat, would become less
      active following particularly variable sequences of interval-lengths in a
      variable interval schedule. From a large dataset of holepokes and tray-reports by
      rats in a variable interval reinforcement schedule, we extracted numerous short
      sequences of intervals on the basis of the first, second, and third derivatives
      of reinforcement timing (i.e. rate, acceleration, and jerk) in recent intervals.
      Sets of selected intervals were compared with one another to elucidate the effect
      of these different derivatives on behaviour in the current interval. Results show
      that SHR are more active after richer recent reinforcement; after decelerating
      reinforcers; and after predictable reinforcers. The hypothesis is supported. In
      conclusion, SHR behaviour largely complies with the Extended Temporal Difference
      model which in turn has been previously validated against published data in ADHD.
      The Extended TD model therefore is able to account for two species' behaviour in
      a wide range of experimental paradigms. SHR are similar in several respects to
      group averages of children with ADHD, except that SHR have reduced variability
      and perform actions faster than controls. Hyperactivity in the SHR is very
      dependent on momentary environmentally determined states, which is an important
      area for future investigation of ADHD.

PMID- 18824036
TI  - Dynamic behavioural changes in the Spontaneously Hyperactive Rat: 1. Control by
      place, timing, and reinforcement rate.
AB  - Several existing theoretical models of Attention Deficit Hyperactivity Disorder
      (ADHD) predict that a high or low learning rate contributes to some cases of
      ADHD; and that this is controlled by the dopamine signal. The Spontaneously
      Hypertensive (Hyperactive) Rat has an abnormal Dopamine Transporter (DAT), which
      is likely to be hypofunctional, thereby increasing the dopamine concentration and
      the learning rate. We therefore test the prediction that the SHR learns too fast.
      Using a variable interval reinforcement schedule, we looked for increased
      responding within each interval, at around the durations of the last three
      intervals. At the time predicted by the previous interval, SHR responded
      significantly (10%) more than their baseline rate, and control WKY rats similarly
      less than their baseline. At the time predicted by the second (and third)
      previous intervals, there were minor trends (and no change) in the same
      direction. In summary, at the times predicted, SHR respond more than control
      rats. The effect size is insufficient to account for all the differences from
      control rats, such as their nearly threefold greater operant responding. At the
      times when SHR increase responding, WKY suppress it. This demonstrates similar
      learning to the SHR but the opposite response, probably due to anxiety about the
      bang accompanying reinforcer delivery: WKY are known to have a very negative
      response to stress. Interval schedules with randomised interval lengths have
      considerable potential for assessing multiple causes of behaviour, particularly
      those acting over short timecourses. Alterations in learning rate are not a
      sufficient explanation for either SHR or ADHD difference from controls.

PMID- 18824037
TI  - Development of novel real-time PCR assays for detecting DNA virus infections in
      psittaciform birds.
AB  - Viral diseases of psittacine birds are detected presently by PCR. However,
      conventional PCR methods are not quantitative and the products can sometimes
      include non-specific products of the same size. To avoid these problems, real
      time PCR assays based on the SYBR Green assay system were developed for the
      detection and quantitation of four virus diseases of psittacine birds: psittacine
      beak and feather disease, avian polyomavirus infection, psittacid herpesvirus
      infection, and psittacine adenovirus infection. Up to 1x10(2) copies of virus DNA
      were detected, indicating that these assays are as sensitive as conventional PCR
      assays. The assays are specific because they did not amplify any other pathogens
      including other viruses, bacteria, and fungi in psittacine birds. The assays
      measured successfully virus loads in clinical samples (blood, feathers, and
      tissues), showing that these specimens were suitable targets for the detection
      and quantitation of viral DNA in psittacine birds.

PMID- 18824038
TI  - Treating lysosomal storage disorders: current practice and future prospects.
AB  - There are over 40 human disease states that are caused by defects in various
      aspects of lysosomal function. Over the past two decades there has been dramatic
      progress in the development and evaluation of therapies for lysosomal storage
      disorders, several of which are now in routine clinical use or in clinical
      trials. The greatest current challenge is in developing effective therapies for
      treating the CNS manifestations of these complex disorders. In this article, we
      will review the current therapies/approaches being considered for treating
      lysosomal storage diseases and give a perspective on the scientific, medical,
      social and ethical issues they raise.

PMID- 18824039
TI  - Dynamic behavioural changes in the Spontaneously Hyperactive Rat: 2. Control by
      novelty.
AB  - An important aspect of attention deficit hyperactivity disorder (ADHD) is its
      temporary amelioration by novelty and by stimulant medication. Extant learning
      based accounts of ADHD are unable to account for the temporary amelioration
      effect. One possible mechanism is a drive for novelty. Computational simulations
      have previously shown that such a drive can result from a "dopamine appetite".
      Empirical demonstration of such a process requires, as a first step, the
      development of standard criteria for identifying drive-based, versus learning
      based, changes in behaviour. Using a variable-interval reinforcement schedule, we
      looked over a range of timescales for behavioural changes showing putative
      characteristics of drives, namely: low information content, unidirectionality,
      saturability, spontaneous reversibility in less than a day, and cycle stability.
      SHR lacks normal down-regulation of responding when the schedule becomes sparser.
      SHR appears to be re-learning the schedule length during the days of each
      calendar week. SHR hyperactivity is specific to the operant and develops
      gradually over the first five minutes of each session. Empirical within-session
      results were replicated by a simple simulation containing two interacting reward
      systems, one for water and the other for stimulation (including novelty). To
      summarise, enhanced sensation-seeking (or a subtype of it, novelty-seeking)
      provides the best available account of changes in SHR activity within sessions,
      though not of changes over longer timecourses. Sensation-seeking appears to be
      associated with low anxiety in the SHR. SHR propensity to display multiple
      influences on their behaviour makes them ideal for further pharmacological,
      genetic, and behavioural investigation.

PMID- 18824040
TI  - Effects of cortisol on emotional but not on neutral memory are correlated with
      peripheral glucocorticoid sensitivity of inflammatory cytokine production.
AB  - Cortisol responses to stress have important physiological effects on several
      target tissues throughout the body, including the central nervous system and the
      immune system. The ability of target tissues to receive cortisol signals has been
      shown to vary between individuals and over time. Conflicting data exist on
      whether different target tissues' glucocorticoid (GC) sensitivity is related. In
      a double-blind, placebo-controlled design, n=19 participants (n=15 men, n=4
      women) received an oral dose of 30 mg of cortisol and placebo in randomized
      order. Memory retrieval of previously learned neutral and emotional words was
      tested after cortisol or placebo application. Peripheral GC sensitivity was
      tested by measuring in-vitro stimulated production of interleukin-6 (IL-6) in
      whole blood before and after cortisol vs. placebo application. Cortisol treatment
      reduced retrieval of neutral and emotional words (marginally significant at
      p=0.07), and significantly reduced stimulated IL-6 production (p<0.001). Relative
      suppression of IL-6 production was associated with impairment of memory retrieval
      of emotional (r=0.48; p=0.039), but not neutral words (r=-0.17; p=0.48). In
      summary, results show an association of peripheral glucocorticoid sensitivity
      with emotional, but not neutral, memory retrieval. Given that these findings can
      be extended to clinical populations, the association of peripheral glucocorticoid
      sensitivity with emotional memory retrieval might have important implications for
      understanding and treatment of stress-related disorders.

PMID- 18824041
TI  - Evaluation of five commercial nucleic acid extraction kits for their ability to
      inactivate Bacillus anthracis spores and comparison of DNA yields from spores and
      spiked environmental samples.
AB  - This study evaluated five commercial extraction kits for their ability to recover
      DNA from Bacillus anthracis spores and spiked environmental samples. The kits
      evaluated represent the major types of methodologies which are commercially
      available for DNA or total nucleic acid extraction, and included the ChargeSwitch
      gDNA Mini Bacteria Kit, NucliSens Isolation Kit, Puregene Genomic DNA
      Purification Kit, QIAamp DNA Blood Mini Kit, and the UltraClean Microbial DNA
      Isolation Kit. Extraction methods were performed using the spores of eight
      virulent strains of B. anthracis. Viability testing of nucleic acid extracts
      showed that the UltraClean kit was the most efficient at depleting samples of
      live B. anthracis spores. TaqMan real-time PCR analysis revealed that the
      NucliSens, QIAamp and UltraClean kits yielded the best level of detection from
      spore suspensions. Comparisons of processed samples from spiked swabs and three
      powder types indicated that DNA extraction using the UltraClean kit resulted in
      the most consistently positive results and the lowest limit of detection. This
      study demonstrated that different nucleic extraction methodologies, represented
      here by various commercial extraction kits, differ in their ability to inactivate
      live B. anthracis spores as well as DNA yield and purity. In addition, the
      extraction method used can influence the sensitivity of real-time PCR assays for
      B. anthracis.

PMID- 18824042
TI  - MLPA diagnostics of complex microbial communities: relative quantification of
      bacterial species in oral biofilms.
AB  - A multitude of molecular methods are currently used for identification and
      characterization of oral biofilms or for community profiling. However, multiplex
      PCR techniques that are able to routinely identify several species in a single
      assay are not available. Multiplex Ligation-dependent Probe Amplification (MLPA)
      identifies up to 45 unique fragments in a single tube PCR. Here we report a novel
      use of MLPA in the relative quantification of targeted microorganisms in a
      community of oral microbiota. We designed 9 species specific probes for:
      Actinomyces gerencseriae, Actinomyces naeslundii, Actinomyces odontolyticus,
      Candida albicans, Lactobacillus acidophilus, Rothia dentocariosa, Streptococcus
      mutans, Streptococcus sanguinis and Veillonella parvula; and genus specific
      probes for selected oral Streptococci and Lactobacilli based on their 16S rDNA
      sequences. MLPA analysis of DNA pooled from the strains showed the expected
      specific MLPA products. Relative quantification of a serial dilution of equimolar
      DNA showed that as little as 10 pg templates can be detected with clearly
      discernible signals. Moreover, a 2 to 7% divergence in relative signal ratio of
      amplified probes observed from normalized peak area values suggests MLPA can be a
      cheaper alternative to using qPCR for quantification. We observed 2 to 6 fold
      fluctuations in signal intensities of MLPA products in DNAs isolated from
      multispecies biofilms grown in various media for various culture times.
      Furthermore, MLPA analyses of DNA isolated from saliva obtained from different
      donors gave a varying number and intensity of signals. This clearly shows the
      usefulness of MLPA in a quantitative description of microbial shifts.

PMID- 18824043
TI  - Artificial neural networks in prediction of antifungal activity of a series of
      pyridine derivatives against Candida albicans.
AB  - Quantitative structure-activity relationships (QSAR) studies of antifungal
      activity against Candida albicans of a large series of new pyridine derivatives
      were conducted with the use of artificial neural networks (ANNs). The application
      of ANNs has been provided with respect to the prediction of antimicrobial potency
      of new pyridine derivatives based on their structural descriptors generated by
      calculation chemistry. Antifungal activity against C. albicans has been related
      to a number of physicochemical and structural parameters of the pyridine
      derivatives investigated. The activity was expressed as logarithm of the
      reciprocal of the minimal inhibitory concentrations, log 1/MIC. Molecular
      descriptors of agents were obtained from structure fragment reference databases
      and by quantum-chemical calculations combined with molecular modeling. A high
      correlation resulted between the ANN predicted antifungal activity, log
      1/MIC(pred), and that one from biological experiments, log 1/MIC(exp), for the
      data used in the testing set of pyridine was obtained with correlation
      coefficient, R, on the level of 0.9112.

PMID- 18824044
TI  - Proteomic analysis of curdlan-producing Agrobacterium sp. in response to pH
      downshift.
AB  - During batch cultivation of Agrobacterium sp. ATCC 31750, proteome analysis in
      response to a pH downshift from 7.0 to 5.5 was carried out using two-dimensional
      electrophoresis and matrix-assisted laser desorption-ionization-time of flight
      mass spectrometry. When the pH of the exponentially growing Agrobacterium sp.
      culture was downshifted to pH 5.5, the synthesis level of 27 intracellular
      proteins showed significant changes in level over a prolonged period of time
      compared with the batch culture controlled at pH 7.0. In particular, the
      intracellular protein level of the beta-1,3-glucan synthase catalytic subunit,
      UTP-glucose-1-phosphate uridylyltransferase, and phosphoglucomutase, which are
      key metabolic enzymes in the curdlan biosynthesis pathway, were more than 10-, 3-
      and 17-times higher in the low pH culture. On the other hand, the level of
      orotidine5-phosphate decarboxylase (conversion of OMP to UMP) was significantly
      up-regulated after pH downshift. The accumulation of UMP may direct the metabolic
      flow towards the biosynthetic route of UTP, which is a key metabolic precursor
      for UDP-glucose. Therefore, it is possible that increase of cellular metabolic
      enzymes during pH downshift culture can enhance the metabolic flux of the
      biosynthesis of key precursor, such as UTP- and UDP-glucose, resulting in an
      increase in curdlan biosynthesis.

PMID- 18824045
TI  - Does vivid emotional imagery depend on body signals?
AB  - The recall and re-experiencing of a personal emotional event (emotional imagery)
      are thought to evoke neural activity in the central nervous system that can
      affect the physiology of bodily states. It has been proposed that the more active
      the neural systems previously engaged in the emotional experience, and the more
      active the bodily state associated with that experience, the more vivid the
      emotional imagery is. The sympathetic nervous system (SNS) and the
      gastrointestinal system (GI) are engaged in emotional reactions. On this basis,
      we hypothesized that vivid emotional imagery would be accompanied by strong
      increases in gastrointestinal and sympathetic nervous system activity. To test
      this hypothesis, 17 healthy participants performed emotional imagery of strong
      autobiographical memories involving various emotional states (happy, fear,
      disgust, sadness, anger). SNS and GI changes, measured by skin conductance and
      electrogastrogram, respectively, correlated positively with subjective ratings of
      arousal during the imagery. However, the SNS changes did not correlate with
      ratings of emotional imagery vividness, and even more intriguingly, the GI
      changes correlated strongly and negatively with vividness ratings. To account for
      these findings, we propose that in highly vivid imagery experience, the central
      nervous system is simulating the whole emotional experience strongly, and bodily
      information plays a lesser role. In low vivid imagery experience, the central
      nervous system is not simulating very strongly the emotional experience, and
      information coming from the body (including the GI system) plays a greater role.
      This interpretation is set forth in the context of Damasio's [Damasio, A., (1999)
      The feeling of what happens: body and emotion in the making of consciousness,
      Orlando, Fl, Harcourt.] theoretical framework, which predicts such a dissociation
      between a "body loop" and an "as if body loop" for the experiencing and re
      experiencing of emotions and feelings.

PMID- 18824046
TI  - Recognition without awareness in a patient with simultanagnosia.
AB  - We report a psychophysiological study of "recognition without awareness" in
      patient 2354, who had severe but circumscribed atrophy in the occipitoparietal
      region bilaterally (caused by visual-variant Alzheimer's disease, documented by
      structural and functional neuroimaging) and an accompanying Balint syndrome that
      prevented her from recognizing the emotional valence of many highly charged
      negative visual scenes (e.g., a burned body). Despite this lack of overt
      recognition, patient 2354 nonetheless generated large amplitude skin conductance
      responses to highly charged negative pictures, demonstrating the same kind of
      recognition without awareness that has been reported previously in patients with
      bilateral occipitotemporal dysfunction and prosopagnosia [e.g., Tranel, D., &
      Damasio, A. R. (1985). Knowledge without awareness: an autonomic index of facial
      recognition by prosopagnosics. Science, 228, 1453-1454.]. Our case complements
      both previous evidence of covert, nonconscious recognition in patients with
      prosopagnosia, and previous behavioral studies of patients with Balint syndrome
      that have shown evidence of "preattentive" visual processing. The findings add to
      the small but important set of empirical observations regarding nonconscious
      visual processing in neurological patients, and indicate that recognition without
      awareness can occur in the setting of dorsal visual stream dysfunction and Balint
      syndrome. The findings in our patient suggest that she has patent pathways from
      higher-order visual cortices to autonomic effectors in the amygdala or
      hypothalamus, even though the results of such information processing are not made
      available to conscious awareness.

PMID- 18824047
TI  - A neuroanatomical dissociation for emotion induced by music.
AB  - Does feeling an emotion require changes in autonomic responses, as William James
      proposed? Can feelings and autonomic responses be dissociated? Findings from
      cognitive neuroscience have identified brain structures that subserve feelings
      and autonomic response, including those induced by emotional music. In the study
      reported here, we explored whether feelings and autonomic responses can be
      dissociated by using music, a stimulus that has a strong capacity to induce
      emotional experiences. We tested two brain regions predicted to be differentially
      involved in autonomic responsivity (the ventromedial prefrontal cortex) and
      feeling (the right somatosensory cortex). Patients with damage to the
      ventromedial prefrontal cortex were impaired in their ability to generate skin
      conductance responses to music, but generated normal judgments of their
      subjective feelings in response to music. Conversely, patients with damage to the
      right somatosensory cortex were impaired in their self-rated feelings in response
      to music, but generated normal skin-conductance responses to music. Control tasks
      suggested that neither impairment was due to basic defects in hearing the music
      or in cognitively recognizing the intended emotion of the music. The findings
      provide evidence for a double dissociation between feeling emotions and autonomic
      responses to emotions, in response to music stimuli.

PMID- 18824048
TI  - Structure-activity studies of AtPep1, a plant peptide signal involved in the
      innate immune response.
AB  - AtPep1, a 23-amino acid peptide recently isolated from Arabidopsis leaves,
      induces the expression of the genes encoding defense proteins against pathogens.
      We investigated the structure-activity relationship of AtPep1 with its receptor,
      a 170 kDa leucine-rich repeat receptor kinase (AtPEPR1) by utilizing a suspension
      cell assay (the alkalinization assay). Binding of AtPep1 to AtPEPR1 on the cell
      surface is accompanied by an increase in the pH of Arabidopsis suspension cell
      media by 1 pH unit in 15 min with a half-maximal response of 0.25 nM. Sequential
      removal of N-terminal amino acids had little effect on activity until the peptide
      was reduced to 15 amino acids [AtPep1(9-23)], which decreased the activity by
      less than one order of magnitude. Activity was completely abolished when nine C
      terminal amino acids remained. Removal of the C-terminal asparagine from AtPep1(9
      23), resulted in a decrease in activity (12 max approximately 100 nM). AtPep1(9
      23) was used for alanine-substitution analysis and revealed two important
      residues for activity, a serine, [A(15)]AtPep1(9-23) (12 max approximately 10nM),
      and a glycine, [A(17)]AtPep1(9-23) (12 max approximately 1000 nM). Neither
      [A(17)]AtPep1(9-23) nor the C-terminal truncated AtPep1, AtPep1(9-22), were able
      to compete with AtPep1(9-23) in the alkalinization assay. The importance of the
      glycine residue for binding to the AtPep receptor was also confirmed by
      competition assays using radiolabeled AtPep1. d-Alanine or 2-methylalanine
      substituted at the glycine position displayed only a slight decrease in activity
      whereas l- and d-proline substitution caused a loss of activity. Homologs of
      AtPep1 identified in Arabidopsis and other species revealed a strict conservation
      of the glycine residue.

PMID- 18824049
TI  - Evolution and selection of human leukocyte antigen alleles by Plasmodium
      falciparum infection.
AB  - Infection by Plasmodium falciparum malaria was one of the major driving forces
      for the selection of various genes, some of which might be involved in protection
      against this infection. The human leukocyte antigen (HLA) system is a highly
      polymorphic supergene complex with extensive diversity across different
      populations. In areas traditionally endemic for malaria for centuries, there
      seems to be some selection of certain HLA alleles that may somehow be involved in
      protection against the infection. One of the major conundrums is the lack of
      homogeneity in the HLA alleles selected by P. falciparum across different
      populations. Various factors like microheterogeneity in parasite species, genetic
      drift in parasitic antigens, varying intensities of transmission, different
      polymorphisms of red cell antigens, and diversity in the HLA system have exerted
      selection pressure, which probably determined the emergence of different dominant
      HLA antigens in different endemic populations. The complex life cycle of P.
      falciparum, with different antigens becoming important at different phases of the
      cycle and invasion of different tissues causing different clinical manifestations
      of the same disease, is also another significant factor contributing to a
      selection pattern. Evolutionary selection pressure probably selected different
      HLA antigens for modulations of different components of the disease as well as
      the severity of the disease. A coevolution, where the parasite polymorphisms meet
      the host heterogeneity, is likely to have occurred, resulting in the selection of
      a few HLA antigens associated with P. falciparum infection. Data might have been
      overwhelmed by the noise of additional selection pressure exerted by other
      infectious agents prevalent in endemic areas of P. falciparum malaria.

PMID- 18824050
TI  - Differential astroglial activation in 6-hydroxydopamine models of Parkinson's
      disease.
AB  - In rat models of Parkinson's disease, injections of 6-hydroxydopamine (6-OHDA)
      into different areas of the basal ganglia result in dopaminergic
      neurodegeneration in the substantia nigra. The extent and time course of the
      dopaminergic lesions varies between the models. While the effects on neurons have
      been extensively studied, little is known about the effects on astrocytes. We
      compared astrocytic activation (i.e. increase in number and staining intensity of
      glial fibrillary acidic protein immunoreactive cells) at the injection site and
      in downstream structures of the motor loop, i.e. the globus pallidus (GP) and the
      subthalamic nucleus (STN) following 6-OHDA lesion of the medial forebrain bundle
      (MFB) or the striatum. Lesions in both regions resulted in astrocytic activation
      at the lesion site, but their remote effects varied. MFB injections caused
      astrocytic activation in the ipsi- and contralateral striatum, whereas striatal
      injections resulted in astrocytic activation in the GP and STN. Since 6-OHDA
      injections into the MFB and the striatum result in complete and partial SNc
      lesions, respectively, we hypothesize that communication links exist between
      astrocytes, or between neurons and astrocytes, along neuronal pathways that
      transmit activating signals in response to neuronal damage-but only if the
      neuronal pathways are at least partially intact.

PMID- 18824051
TI  - Differential inhibition of globus pallidus neurons by electrical or chemical
      stimulation of the striatum.
AB  - The reciprocal connections between the globus pallidus (GP) and other basal
      ganglia (BG) nuclei indicate that the GP plays a significant role in controlling
      the neuronal activity of the entire BG; in turn, the activity of GP neurons is
      controlled by several major inputs that involve the striatum. Here, we determined
      the relative contributions of the selective (chemical) or massive (electrical)
      activation of the striatal GABAergic transmission to the GP spiking activity. In
      vivo extracelullar single-unit recordings were performed in the GP of ketamine
      anesthetized rats. Both chemical and electrical stimulation of the striatum
      caused a significant GP spike rate reduction; however, chemical stimulation of
      the striatum produced a complete firing arrest on most GP neurons, something not
      seen with electrical stimulation. In addition, chemical stimulation of the
      striatum with NMDA evoked a significant long-lasting post-inhibitory spike rate
      increase, an effect that was not seen under glutamate infusion or electrical
      stimulation. Furthermore, the selective intrapallidal blockade of AMPA/kainate
      glutamate receptors facilitates the inhibitory effect of intrastriatal electrical
      stimulation. Our results suggest a differential effect of electrical or chemical
      stimulation of the striatum on the spiking activity of GP neurons, which involves
      the activation of intrapallidal AMPA/kainate receptors and striatal en passant
      fibers.

PMID- 18824052
TI  - Structure-based fragment shuffling of two fungal phytases for combination of
      desirable properties.
AB  - Aspergillus niger NRRL 3135 phytase (Anp) and Aspergillus fumigatus ATCC 13073
      phytase (Afp) are quite different but mutually complementary in many properties.
      A semi-rational protein engineering strategy based on 3D structure and sequence
      alignment was used to take advantage of the desirable characteristics of both
      enzymes. Each phytase was divided into seven fragments, including regions I-VII
      (I, 1-47; II, 59-133; III, 139-172; IV, 178-237; V, 246-329; VI338-381; VII, 404
      444). The equivalent regions were swapped to construct an array of chimeras.
      Among the functional chimeras expressed in the yeast Pichia pastoris, novel
      phytases with combinations of the most desirable properties, including heat
      resistance, were obtained. Correlations of individual regions with detailed
      differences were established by systematic evaluation of the substitutions.
      Regions II and VI contributed to the difference in specific activity at pH 5.0.
      Regions IV and V of Anp fully accounted for its second pH optimum at pH 2.5. Most
      influences of substitutions were additive, except those of regions V and VI.
      Exchanging both regions led to different impacts upon K(m) and activity at
      approximately pH 4.0 compared with the replacement of either.

PMID- 18824053
TI  - Local lymph node assay (LLNA): comparison of different protocols by testing skin
      sensitizing epoxy resin system components.
AB  - Thirteen epoxy resin system components were tested in the LLNA with regard to
      their sensitizing potency. Lymph node stimulation was quantified not only by
      measuring the incorporation of [3H]-thymidine into the ear lymph nodes but also
      the counts of cells recovered from these organs. Equivalent figures were obtained
      with both endpoints used for the evaluation of lymph node cell proliferation if
      the reference stimulation indices were adjusted. When dissolved in acetone, all
      test substances showed skin-sensitizing potential, mainly on the boundary between
      "strong" and "moderate" according to common potency evaluation schemes. Replacing
      acetone with acetone/olive oil (4:1) as a vehicle for four selected test items,
      resulted in considerably lower estimated concentrations for sensitization
      induction. The challenges in comparing the results obtained by different LLNA
      variations are discussed.

PMID- 18824054
TI  - Interaction of zinc with antidepressants in the tail suspension test.
AB  - The antidepressant-like effect of zinc has been shown in several animal models of
      depression. In this study, zinc chloride (ZnCl2) was given alone or in
      combination with different classes of antidepressants by oral route (p.o.) to
      mice and the behavioral response in the tail suspension test (TST), a predictive
      test of antidepressant action, was investigated. ZnCl2 at a dose of 10 and 30
      mg/kg, p.o., reduced the immobility time in the TST, without affecting the
      locomotor activity in open-field test. The antidepressants fluoxetine,
      paroxetine, imipramine, desipramine and bupropion produced a significant
      reduction in the immobility time in TST at the doses of 10, 1, 1, 1 and 10 mg/kg,
      p.o., respectively. The combined treatment of sub-effective doses of ZnCl2 (1
      mg/kg) with sub-effective doses of fluoxetine (5 mg/kg), paroxetine (0.1 mg/kg),
      desipramine (0.1 mg/kg), imipramine (0.1 mg/kg) or bupropion (1 mg/kg) induced a
      significant reduction in the immobility time in the TST when compared with the
      groups treated with ZnCl2 or with antidepressants alone. The treatment with sub
      effective doses of ZnCl2 and antidepressants alone or in combination did not
      affect the locomotion in open-field test, except that desipramine alone reduced
      the ambulation. The results first indicate that ZnCl2 administered by p.o. route
      produces an antidepressant-like effect in the TST. Moreover, synergistic effects
      of zinc with antidepressants were shown in the TST, suggesting that an
      improvement in the response to the antidepressant therapy occurs when zinc is
      combined with different classes of antidepressants.

PMID- 18824055
TI  - Lithium as a treatment of clozapine-induced neutropenia: a case report.

PMID- 18824056
TI  - Bovine viral diarrhea virus is a suitable viral vector for stable expression of
      heterologous gene when inserted in between N(pro) and C genes.
AB  - Bovine viral diarrhea virus (BVDV) is a group of small enveloped viruses with a
      single-stranded, positive-oriented RNA genome of approximately 12.3 kb. BVDV
      genome directs the production of a viral polyprotein that is subsequently cleaved
      to release the mature viral proteins. To explore the potential of using BVDV as
      viral vector for stable expression of heterologous genes, eGFP2A was inserted in
      between N(pro) and C genes of a noncytopathic type-I BVDV strain SD1. eGFP2A was
      designed with eGFP protein in frame fused to the N terminus of the foot-and-mouth
      disease virus 2A protease. This strategy promised not only the correct processing
      of both viral N(pro) and C protein but also releasing of the chimeric protein
      from the nascent viral polyprotein. The recombinant reporter virus was
      successfully rescued in MDBK cells. In vitro study showed that eGFP2A protein, as
      expected, was expressed and processed properly from the nascent viral
      polyprotein. The reporter virus was similar to wt SD1 in viral RNA replication
      and protein expression and comparable to wt SD1 in growth kinetics except that
      this virus had a peak virus titer approximately 0.5 log(10) lower and a maximum
      yield about 4h later than wt SD1. In summary, these results indicated that BVDV
      is a suitable viral vector for stable expression of heterologous genes when
      inserted in between N(pro) and C genes.

PMID- 18824057
TI  - Protective mechanisms of Aralia continentalis extract against tert-butyl
      hydroperoxide-induced hepatotoxicity: in vivo and in vitro studies.
AB  - In the present work, we investigated the protective effects of the ethanol
      extract of Aralia continentalis roots (AC) on tert-butyl hydroperoxide (t-BHP)
      induced hepatotoxicity in a cultured Hepa1c1c7 cell line and in mouse liver.
      Pretreatment with AC prior to the administration of t-BHP significantly prevented
      the increase in serum levels of hepatic enzyme markers (ALT, AST) and lipid
      peroxidation and reduced oxidative stress, as measured by glutathione content, in
      the liver. Histopathological evaluation of the livers also revealed that AC
      reduced the incidence of liver lesions. The in vitro study showed that AC
      significantly reduced t-BHP-induced oxidative injury in Hepa1c1c7 cells, as
      determined by cell cytotoxicity, intracellular glutathione content, lipid
      peroxidation, reactive oxygen species (ROS) levels, and caspase-3 activation.
      Also, AC up-regulated phase II genes including heme oxygenase-1 (HO-1),
      NAD(P)H:quinone reductase, and glutathione S-transferase. Moreover, AC induced
      Nrf2 nuclear translocation and ERK1/2 and p38 activation, pathways that are
      involved in inducing Nrf2 nuclear translocation. Taken together, these results
      suggest that the protective effects of AC against t-BHP-induced hepatotoxicity
      may, at least in part, be due to its ability to scavenge ROS and to regulate the
      antioxidant enzyme HO-1 via the ERK1/2 and p38/Nrf2 signaling pathways.

PMID- 18824058
TI  - Isolation, characterization, molecular cloning and modeling of a new lipid
      transfer protein with antiviral and antiproliferative activities from Narcissus
      tazetta.
AB  - A fetuin-binding peptide with a molecular mass of about 9kDa (designated NTP) was
      isolated and purified from the bulbs of Chinese daffodil, Narcissus tazetta var.
      chinensis L., by gel filtration and high-performance liquid chromatography, after
      removing the mannose-binding proteins by mannose-agarose column. Molecular
      cloning revealed that NTP contained an open reading frame of 354bp encoding a
      polypeptide of 118 amino acids which included a 26-amino-acid signal peptide. An
      analysis of the deduced amino acid sequence of NTP shows considerable sequence
      homology to the non-specific lipid transfer proteins (nsLTPs) of certain plants.
      Model of the three-dimensional (3D) structure of NTP exhibits an internal
      hydrophobic cavity which can bind lipid-like molecules and transfer a wide range
      of ligands. As a member of the putative non-specific lipid transfer protein of N.
      tazetta, NTP did not possess hemagglutinating activity toward rabbit
      erythrocytes. In a cell-free system, it could arrest the protein synthesis of
      rabbit reticulocytes. Using the in vitro antiviral assays, NTP could
      significantly inhibit the plaque formation by respiratory syncytial virus (RSV)
      and the cytopathic effect induced by influenza A (H1N1) virus, as well as the
      proliferation of human acute promyelocytic leukemia cells (HL-60).

PMID- 18824059
TI  - Induction of drug metabolism: species differences and toxicological relevance.
AB  - A large number of drugs and other chemicals have been shown to induce hepatic
      microsomal cytochrome P450 (CYP) forms in experimental animals and humans. Most
      CYP forms are induced by receptor-mediated mechanisms leading to an increase in
      gene transcription. Important nuclear receptors involved in the induction of
      CYP1A, CYP2B, CYP3A and CYP4A subfamily forms comprise, respectively, the aryl
      hydrocarbon receptor, the constitutive androstane receptor, the pregnane X
      receptor and the peroxisome proliferator-activated receptor alpha. Hepatic CYP
      form induction can be assessed by in vivo, ex vivo and in vitro methods.
      Significant species differences can exist in the enzyme induction response to a
      given chemical and also in the toxicological consequences of induction. Hepatic
      CYP form induction in humans may lead to clinically important drug-drug
      interactions. In rodents hepatic CYP form induction can be associated with the
      formation of tumours by non-genotoxic modes of action in the liver, thyroid and
      other tissues.

PMID- 18824060
TI  - A SARS DNA vaccine induces neutralizing antibody and cellular immune responses in
      healthy adults in a Phase I clinical trial.
AB  - BACKGROUND: The severe acute respiratory syndrome (SARS) virus is a member of the
      Coronaviridae (CoV) family that first appeared in the Guangdong Province of China
      in 2002 and was recognized as an emerging infectious disease in March 2003. Over
      8000 cases and 900 deaths occurred during the epidemic. We report the safety and
      immunogenicity of a SARS DNA vaccine in a Phase I human study. METHODS: A single
      plasmid DNA vaccine encoding the Spike (S) glycoprotein was evaluated in 10
      healthy adults. Nine subjects completed the 3 dose vaccination schedule and were
      evaluated for vaccine safety and immune responses. Immune response was assessed
      by intracellular cytokine staining (ICS), ELISpot, ELISA, and neutralization
      assays. RESULTS: The vaccine was well tolerated. SARS-CoV-specific antibody was
      detected by ELISA in 8 of 10 subjects and neutralizing antibody was detected in
      all subjects who received 3 doses of vaccine. SARS-CoV-specific CD4+ T-cell
      responses were detected in all vaccinees, and CD8+ T-cell responses in
      approximately 20% of individuals. CONCLUSIONS: The VRC SARS DNA vaccine was well
      tolerated and produced cellular immune responses and neutralizing antibody in
      healthy adults.

PMID- 18824062
TI  - Mild cognitive impairment presenting with delusional misidentification: a case
      report.

PMID- 18824063
TI  - Plasma homocysteine levels in young male patients in the exacerbation and
      remission phase of schizophrenia.
AB  - High levels of homocysteine (Hcy) were suggested to contribute to the
      pathogenesis of schizophrenia. Recent investigations have shown that treatment
      with folic acid, vitamin B-12 and pyridoxine are effective in reducing Hcy levels
      while concomitantly reducing the score of positive and negative symptoms in
      schizophrenic patients. In addition to the availability of nutrients (mainly
      folate, vitamins B6 and B12), plasma Hcy concentrations are dependent on complex
      metabolic regulation that could be disrupted in schizophrenia. This study was
      designed to test the influence of disease activity on plasma Hcy levels. Plasma
      Hcy concentrations were measured in male chronic schizophrenic patients with a
      predominantly positive (SCH (+)) or predominantly negative (SCH (-)) syndrome in
      schizophrenia immediately upon admission to the hospital (exacerbation phase) and
      one month later (remission phase). During this period patients received
      antipsychotic medications without vitamin therapy. The effects of age, duration
      of illness, folate and B12 concentrations, as well as smoking and coffee
      consumption habits on the observed changes were evaluated. Age- and sex-matched
      subjects were included in the control group. In the control group plasma Hcy
      concentration was 8.75+/-1.84 micromol/L. In the exacerbation phase plasma Hcy
      concentrations were significantly increased both in SCH (+) (14.91+/-6.19
      micromol/L) and SCH (-) groups (12.8+/-3.27 micromol/L). There was no difference
      in plasma Hcy concentrations between SCH (+) and SCH (-) patients. Serum folate
      and B12 concentrations were not significantly different in any of the
      investigated groups of subjects. The plasma Hcy concentrations could not be
      correlated with age, duration of illness, the score of positive symptoms or the
      concentration of folate and vitamin B12. A positive correlation was found between
      plasma Hcy level and score of negative symptoms in both groups of patients. No
      correlation was found between smoking or coffee consumption habits and plasma Hcy
      concentrations. All patients exhibited decreased plasma Hcy levels in the
      remission phase of the illness, with a mean decrease of 2.68+/-1.57 micromol/L.
      Folate and B12 levels did not differ in the exacerbation and remission phases of
      the illness. The significant decrease of plasma Hcy levels, without changes in
      folate and vitamin B12 concentrations in the remission phase of schizophrenia,
      could indicate an influence of a pathogenetic process involved in schizophrenia
      on Hcy metabolism.

PMID- 18824061
TI  - Seeing the invisible: the scope and limits of unconscious processing in binocular
      rivalry.
AB  - When an image is presented to one eye and a very different image is presented to
      the corresponding location of the other eye, the two images compete for conscious
      representations, such that only one image is visible at a time while the other is
      suppressed. Called binocular rivalry, this phenomenon and its deviants have been
      extensively exploited to study the mechanism and neural correlates of
      consciousness. In this paper, we propose a framework - the unconscious binding
      hypothesis - to distinguish unconscious processing from conscious processing.
      According to this framework, the unconscious mind not only encodes individual
      features but also temporally binds distributed features to give rise to cortical
      representations; unlike conscious binding, however, unconscious binding is
      fragile. Under this framework, we review evidence from psychophysical and
      neuroimaging studies and come to two important conclusions. First, processing of
      invisible features depends on the "level" of the features as defined by their
      neural mechanisms. For low-level simple features, prolonged exposure to visual
      patterns (e.g. tilt) and simple translational motion can alter the appearance of
      subsequent visible features (i.e. adaptation). For invisible high-level features,
      complex spiral motion cannot produce adaptation, nor can objects/words enhance
      subsequent processing of related stimuli (i.e. priming). Yet images of tools can
      activate the dorsal pathway. Second, processing of invisible features has
      functional significance. Although invisible central cues cannot orient attention,
      invisible erotic pictures in the periphery can nevertheless guide attention,
      likely through emotional arousal; reciprocally, the processing of invisible
      information can be modulated by attention.

PMID- 18824064
TI  - Reduced efficacy of fluoxetine following MDMA ("Ecstasy")-induced serotonin loss
      in rats.
AB  - Long-term serotonin (5-HT) neuronal loss is currently a major cause of concern
      associated with recreational use of the substituted amphetamine 3,4
      methylenedioxymethamphetamine (MDMA; "Ecstasy"). Such loss may be problematic
      considering that psychiatric disorders such as depression and anxiety and
      responses to first line treatments for these disorders are associated with 5-HT.
      In this study the effects of prior exposure to MDMA on behavioural and central
      neurochemical changes induced by the serotonin (5-HT) re-uptake inhibitor and
      antidepressant fluoxetine were examined in rats. Animals were administered MDMA
      (10 mg/kg. i.p.) four times daily for two consecutive days. One week later the
      animals were subjected to treatment with fluoxetine (10 mg/kg, i.p.). Fluoxetine
      treatment groups received either acute (saline injections for 20 days followed by
      3 fluoxetine treatments over 24 h) or chronic (once daily fluoxetine for 21 days)
      drug administration. Prior exposure to MDMA resulted in an attenuation of
      fluoxetine-induced swimming behaviour in the modified forced swimming test (FST);
      a behavioural test of antidepressant action. In parallel MDMA treatment resulted
      in significant regional depletions of 5-HT and its metabolite 5
      hydroxyindoleacetic acid (5-HIAA) accompanied by a reduction in cortical [3H]
      paroxetine binding to nerve terminal 5-HT transporters. MDMA-induced 5-HT loss
      was enhanced in animals following chronic fluoxetine administration. Elimination
      of fluoxetine and its metabolite norfluoxetine from the brain abolished this
      interaction between MDMA and fluoxetine treatment. Fluoxetine administration
      reduced both 5-HIAA and the 5-HIAA:5-HT metabolism ratio, which was attenuated in
      animals pre-treated with MDMA. Overall the results show that MDMA induces long
      term 5-HT loss in the rodent brain and consequently diminishes behaviour and
      reductions in 5-HT metabolism induced by the antidepressant fluoxetine. These
      results have potential clinical relevance, suggesting that 5-HT re-uptake
      inhibitors such as fluoxetine may be less effective at treating depression in
      chronic abusers of MDMA.

PMID- 18824065
TI  - Androgens, estrogens, and hydroxysteroid dehydrogenases.
AB  - The task of regulating both production and activity of potent androgens and
      estrogens in human physiology is largely relegated to the hydroxysteroid
      dehydrogenases (HSDs). Although over two dozen enzymes with HSD activities have
      been described, we only understand the physiology of a small number, and for only
      one enzyme has the function been unequivocally determined by the study of human
      mutations. The physiology of the HSDs derive from their enzymatic activities,
      which in turn derive from their respective structures. In general, pairs of
      enzymes that drive steroid flux in opposite directions are found, and we have
      been studying the biochemical principles which enable dichotomous enzymes to
      perform their specific functions. In general, these directional preferences in
      intact cells are governed by relative affinities for nicotinamide adenine
      dinucleotide (phosphate) cofactors [NAD(P)(H)] and concentration gradients of
      these cofactors in subcellular compartments. For the reductive HSDs human
      17betaHSD type 1 and rat AKR1C9, we can attenuate or reverse the directional
      preference in intact cells by site-directed mutagenesis in the cofactor-binding
      domain or by glucose deprivation, but the magnitude of such changes vary with the
      different enzymes.

PMID- 18824066
TI  - Regulation of beta cell replication.
AB  - Beta cell mass, at any given time, is governed by cell differentiation,
      neogenesis, increased or decreased cell size (cell hypertrophy or atrophy), cell
      death (apoptosis), and beta cell proliferation. Nutrients, hormones and growth
      factors coupled with their signalling intermediates have been suggested to play a
      role in beta cell mass regulation. In addition, genetic mouse model studies have
      indicated that cyclins and cyclin-dependent kinases that determine cell cycle
      progression are involved in beta cell replication, and more recently, menin in
      association with cyclin-dependent kinase inhibitors has been demonstrated to be
      important in beta cell growth. In this review, we consider and highlight some
      aspects of cell cycle regulation in relation to beta cell replication. The role
      of cell cycle regulation in beta cell replication is mostly from studies in
      rodent models, but whether these findings can be extended to human beta cells
      remains to be shown.

PMID- 18824067
TI  - Role of the renin-angiotensin system in prostate cancer.
AB  - Prostate cancer is highly prevalent in Western society, and its early stages can
      be controlled by androgen ablation therapy. However, the cancer eventually
      regresses to an androgen-independent state for which there is no effective
      treatment. The renin-angiotensin system (RAS), in particular the octapeptide
      angiotensin II, is now recognised to have important effects on growth factor
      signalling and cell growth in addition to its well known actions on blood
      pressure, fluid homeostasis and electrolyte balance. All components of the RAS
      have been recently identified in the prostate, consistent with the expression of
      a local RAS system in this tissue. This review focuses on the role of the RAS in
      the prostate, and the possibility that this pathway may be a potential
      therapeutic target for the treatment of prostate cancer and other prostatic
      diseases.

PMID- 18824068
TI  - Analysis of cyanogens with resorcinol and picrate.
AB  - The total cyanogenic potential of various substrates (flax seed, stones of peach,
      plum, nectarine and apricot as well as apple seeds, and various model compounds)
      was investigated by using the acid hydrolysis method, picrate method, and a novel
      method based on the reaction of cyanide liberated from plants with resorcinol and
      picrate. The hydrocyanic acid liberated from cyanogens was trapped by using a 1%
      sodium bicarbonate. Then, 1 ml of extract was mixed with 1 ml of working reagent
      containing 160 microg of resorcinol, 320 microg of picric acid, and 30 mg of
      sodium carbonate, and heated on a boiling water bath for 10 min. The absorbance
      was measured at 488 nm in 1cm glass cuvettes at room temperature. The color
      system obeys Beer's law in the range of 0-5 microg ml(-1) total HCN. Using model
      compounds and real samples including replicate analyses on prunasin, the
      resorcinol method proved to be more accurate, reproducible, and especially more
      sensitive than the known spectrophotometric methods such as the acid hydrolysis
      method and the picrate method.

PMID- 18824069
TI  - Effects of salvinorin A on locomotor sensitization to D2/D3 dopamine agonist
      quinpirole.
AB  - Locomotor sensitization induced by the dopamine agonist quinpirole can be
      potentiated by co-treatment with the synthetic kappa opioid agonist U69593. The
      identification of salvinorin A, an active component of the psychotropic sage
      Salvia divinorum, as a structurally different agonist of kappa-opioid receptors
      raised the question of whether this compound would similarly potentiate
      sensitization to quinpirole. Rats were co-treated with 0.5 mg/kg quinpirole and
      either salvinorin A (0.04, 0.4 or 2.0 mg/kg) or U69593 (0.3 mg/kg). Control
      groups were co-treated with vehicle and saline, vehicle and quinpirole (0.5
      mg/kg), or saline and salvinorin A (0.4 mg/kg). Rats were injected biweekly for a
      total of 10 injections and locomotor activity measured after each treatment.
      Results showed that the highest dose of salvinorin A potentiated sensitization to
      quinpirole as did U69593, the middle salvinorin A dose had no effect on
      quinpirole sensitization, and the lowest dose of salvinorin A attenuated
      sensitization to quinpirole. These findings indicate that structural differences
      between salvinorin A and U69593 do not affect the potentiation of quinpirole
      sensitization. Moreover, the opposite effects of high and low salvinorin A doses
      suggest that salvinorin A can produce bidirectional modulation of sensitization
      to dopamine agonists.

PMID- 18824070
TI  - Altered neuronal expression of TASK1 and TASK3 potassium channels in rodent and
      human autoimmune CNS inflammation.
AB  - Multiple sclerosis (MS) and its animal model experimental autoimmune
      encephalomyelitis (EAE) are characterized by T cell-mediated autoimmune
      inflammation of the central nervous system (CNS) leading to oligodendrocyte loss
      and demyelination accompanied by neuronal cell death. Neuronal TWIK-related acid
      sensitive potassium (TASK) channels allow the regulated efflux of potassium ions.
      These channels might either protect neurons in the inflamed CNS by modulating
      electrical excitability or even contribute to inflammatory neurodegeneration
      mediating intracellular potassium depletion. Using a combination of in-situ
      hybridisation and immunofluorescence staining, we found increased neuronal
      expression of TASK1 and TASK3 channels in the optic nerve and decreased
      expression in the spinal cord and thalamus of rats undergoing MOG-induced EAE.
      Inflammatory plaques of human MS patients displayed profoundly lowered expression
      of both TASK isoforms. Thus, regulated expression of TASK channels might
      contribute to a molecular switch between death and survival of neurons in
      autoimmune CNS inflammation.

PMID- 18824071
TI  - Hyperosmolar treatment of soman-induced brain lesions in mice: evaluation of the
      effects through diffusion-weighted magnetic resonance imaging and through
      histology.
AB  - PURPOSE: A convulsive dose of soman induces seizure-related brain damage (SRBD),
      including cerebral edema (CE) and neuronal loss. In the present study on soman
      intoxicated mice, we applied diffusion-weighted magnetic resonance imaging (DW
      MRI) and quantitative histology, and we measured brain water content to
      investigate the antiedematous and neuroprotective efficacies of two hyperosmolar
      treatments: mannitol (Mann) and hypertonic saline (HTS). METHODS: Mice
      intoxicated with soman (172 microg/kg after a protective pretreatment) were
      administered 1 min and 5-h post-challenge an i.v. bolus of saline, of Mann or of
      HTS. 1 day later, mice were examined with DW-MRI and then sacrificed for brain
      histology. Additional animals were intoxicated and treated similarly for the
      measurement of the brain water content (dry/wet weight method). RESULTS: In
      intoxicated controls, a significant decrease of the apparent diffusion
      coefficient (ADC), numerous damaged (eosinophilic) cells, high edema scores, and
      a significant increase in brain water content were detected 24-h post-challenge
      in sensitive brain structures. These soman-induced changes were not significantly
      modified by treatment with Mann or HTS. CONCLUSIONS: Treatment with hyperosmolar
      solutions did not reduce the effects of soman on ADC, on cell damage and on CE.
      Therefore, despite similar treatment protocols, the prominent protection by Mann
      that was previously demonstrated by others in poisoned rats, was not reproduced
      in our murine model.

PMID- 18824072
TI  - Hepatic fibrogenesis: from within and outwith.
AB  - Liver disease is now the fifth commonest cause of death in the United Kingdom and
      the incidence is increasing. Chronic injury to the liver typically due to toxic
      insult, viral infection, immunological or metabolic diseases usually results in a
      stereotypical response with both parenchymal regeneration and wound healing.
      Chronic hepatic injury results in liver fibrosis with eventual progression to
      cirrhosis and end stage liver disease. At this point the majority of the clinical
      complications arise such as portal hypertension and the development of liver
      cancer. If the causative disease can be effectively treated the liver can
      regenerate and at the least partial resolution of liver fibrosis may occur.
      Unfortunately, unless the primary disease can be eradicated there are no specific
      anti-fibrotic treatments in routine clinical use. This highlights the urgent need
      to both increase our understanding of the mechanisms of hepatic fibrogenesis and
      to develop novel therapies to arrest or reverse the fibrotic process. This
      article initially outlines the main cellular pathway of fibrogenesis within the
      liver-the activation of the quiescent hepatic stellate cell into an activated
      myofibroblast phenotype, resulting in the production of fibrillar collagen. We
      will then discuss newly emerging sources of scar forming cells during hepatic
      injury together with the role of hepatic macrophages which have a regulatory
      function in both the formation and resolution of liver fibrosis.

PMID- 18824073
TI  - Testosterone-driven seasonal regulation of vasopressin and galanin in the bed
      nucleus of the stria terminalis of the Djungarian hamster (Phodopus sungorus).
AB  - The sexually dimorphic vasopressin system of the bed nucleus of the stria
      terminalis (BNST) is the most sensitive neurotransmitter system regulated by sex
      steroids in rats and mice. In addition to vasopressin, the BNST neurons also
      express a second neuropeptide, galanin, whose expression also appears to be
      regulated by testosterone in laboratory rodents. Seasonal fluctuations of sex
      steroids in photoperiodic rodents feed back on the brain to regulate the
      expression of sex steroid sensitive genes. The seasonal rhythm of circulating sex
      steroids is generated by photoperiod-controlled melatonin secretion, resulting in
      a seasonal stimulation and involution of the gonads. We have studied the seasonal
      expression of vasopressin and galanin in BNST neurons and their target areas in
      the Djungarian hamster (Phodopus sungorus). Furthermore, we analyzed the effect
      of testosterone on vasopressin and galanin by testosterone supplementation in
      animals where reproduction was inhibited by exposure to a short photoperiod.
      Exposure to short photoperiod induced a major reduction in the expression of
      vasopressin in BNST neurons, as well as in their target areas, the lateral septum
      (LS) and the lateral habenula (LHb). Galanin expression in the BNST and its
      target areas was also strongly reduced, although this reduction did not result in
      an almost complete disappearance of the neuropeptide as observed for vasopressin.
      Testosterone was able to reverse this reduction for both vasopressin and galanin.
      However, while the mRNA expression in BNST neurons recovered within 2-4 days,
      recovery of the neuropeptide immunoreactivity in the target areas, LS and LHb,
      required more than 3 weeks. The photoperiod-driven testosterone rhythm thus
      appears to be a major regulator of extra-hypothalamic vasopressin and galanin in
      the Djungarian hamster. The long delay between mRNA recovery in the cell body and
      the neuropeptide recovery in the target areas may be due to progressive filling
      up of the axon terminals. Alternatively, this delay might be indicative of a
      seasonal structural plasticity.

PMID- 18824074
TI  - The orbitofrontal cortex and beyond: from affect to decision-making.
AB  - The orbitofrontal cortex represents the reward or affective value of primary
      reinforcers including taste, touch, texture, and face expression. It learns to
      associate other stimuli with these to produce representations of the expected
      reward value for visual, auditory, and abstract stimuli including monetary reward
      value. The orbitofrontal cortex thus plays a key role in emotion, by representing
      the goals for action. The learning process is stimulus-reinforcer association
      learning. Negative reward prediction error neurons are related to this affective
      learning. Activations in the orbitofrontal cortex correlate with the subjective
      emotional experience of affective stimuli, and damage to the orbitofrontal cortex
      impairs emotion-related learning, emotional behaviour, and subjective affective
      state. With an origin from beyond the orbitofrontal cortex, top-down attention to
      affect modulates orbitofrontal cortex representations, and attention to intensity
      modulates representations in earlier cortical areas of the physical properties of
      stimuli. Top-down word-level cognitive inputs can bias affective representations
      in the orbitofrontal cortex, providing a mechanism for cognition to influence
      emotion. Whereas the orbitofrontal cortex provides a representation of reward or
      affective value on a continuous scale, areas beyond the orbitofrontal cortex such
      as the medial prefrontal cortex area 10 are involved in binary decision-making
      when a choice must be made. For this decision-making, the orbitofrontal cortex
      provides a representation of each specific reward in a common currency.

PMID- 18824075
TI  - The cognitive functions of the caudate nucleus.
AB  - The basal ganglia as a whole are broadly responsible for sensorimotor
      coordination, including response selection and initiation. However, it has become
      increasingly clear that regions of the basal ganglia are functionally delineated
      along corticostriatal lines, and that a modular conception of the respective
      functions of various nuclei is useful. Here we examine the specific role of the
      caudate nucleus, and in particular, how this differs from that of the putamen.
      This review considers converging evidence from multiple domains including
      anatomical studies of corticostriatal circuitry, neuroimaging studies of healthy
      volunteers, patient studies of performance deficits on a variety of cognitive
      tests, and animal studies of behavioural control. We conclude that the caudate
      nucleus contributes to behaviour through the excitation of correct action schemas
      and the selection of appropriate sub-goals based on an evaluation of action
      outcomes; both processes fundamental to successful goal-directed action. This is
      in contrast to the putamen, which appears to subserve cognitive functions more
      limited to stimulus-response, or habit, learning. This modular conception of the
      striatum is consistent with hierarchical models of cortico-striatal function
      through which adaptive behaviour towards significant goals can be identified
      (motivation; ventral striatum), planned (cognition; caudate) and implemented
      (sensorimotor coordination; putamen) effectively.

PMID- 18824077
TI  - Modulatory effects of seabuckthorn (Hippophae rhamnoides L.) in hypobaric hypoxia
      induced cerebral vascular injury.
AB  - Cerebral edema caused by vascular leakage is a major problem in various injuries
      of the CNS, such as stroke, head injury and high-altitude illness. A common
      feature of all these disorders is the fact that they are associated with tissue
      hypoxia. Hypoxia has been suggested to be a major pathogenic factor for the
      induction of vascular leakage in the brain. The objective of the present study
      was to evaluate potential of seabuckthorn (SBT) (Hippophae rhamnoides L.) seed
      oil in curtailing hypoxia induced transvascular fluid leakage in brain of hypoxia
      exposed rats. Exposure of animals to hypobaric hypoxia (9144 m, 5h) caused a
      significant increase in the transvascular leakage studied by measuring water
      content and leakage of sodium fluorescein dye in the brain. Hypoxic stress also
      significantly enhanced the oxidative stress markers such as free radicals and
      malondialdehyde and it accompanied with decreased levels of antioxidants such as
      glutathione, glutathione peroxidase and superoxide dismutase. Pretreatment of
      animals with SBT seed oil significantly restricted the hypoxia induced increase
      in fluorescein dye leakage suggesting protection against hypoxia induced
      transvascular leakage in the brain. Hypoxia induced increase in the levels of
      free radicals and malondialdehyde were significantly lowered after SBT
      pretreatment. The SBT seed oil pretreatment also resulted in the significantly
      improved hypoxic tolerance as evidenced by increased hypoxic gasping time and
      survival time and decreased plasma catecholamine levels, as compared to hypoxic
      animals. These observations suggest that SBT seed oil possesses significant
      hypoxia protection activity and curtailed hypoxia induced enhanced vascular
      leakage in the brain.

PMID- 18824078
TI  - Tumor necrosis factor-alpha of Red nucleus involved in the development of
      neuropathic allodynia.
AB  - The pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) is
      associated with the generation of inflammatory and neuropathic pain. The current
      study aims to investigate the expression of TNF-alpha in the brain of rats with
      spared nerve injury (SNI), a neuropathic pain model with the lesion of common
      peroneal and tibial nerves. Two weeks following SNI, the immunohistochemical
      results identified that the expression level of TNF-alpha in the Red nucleus (RN)
      of SNI rats was apparently higher than that of sham-operated rats. To further
      study the roles of TNF-alpha in the development of neuropathic pain, different
      doses of anti-TNF-alpha antibody (20, 2.0 and 0.2 MUg/ml) were microinjected into
      the RN contralateral to the nerve injury side of SNI rats. The results showed
      that the 50% paw withdrawal threshold (von Frey test) of SNI rats were increased
      by 20 and 2.0 MUg/ml anti-TNF-alpha antibody as compared with that of the basic
      value and control groups (P<0.05), the analgesic effect lasted for 50 and 30 min,
      respectively. However, no significant analgesic effect was observed after 0.2
      MUg/ml antibody was microinjected into the RN. These results suggest that the TNF
      alpha of RN is involved in the development of neuropathic allodynia in SNI rats.

PMID- 18824076
TI  - Cracking taste codes by tapping into sensory neuron impulse traffic.
AB  - Insights into the biological basis for mammalian taste quality coding began with
      electrophysiological recordings from "taste" nerves and this technique continues
      to produce essential information today. Chorda tympani (geniculate ganglion)
      neurons, which are particularly involved in taste quality discrimination, are
      specialists or generalists. Specialists respond to stimuli characterized by a
      single taste quality as defined by behavioral cross-generalization in conditioned
      taste tests. Generalists respond to electrolytes that elicit multiple aversive
      qualities. Na(+)-salt (N) specialists in rodents and sweet-stimulus (S)
      specialists in multiple orders of mammals are well characterized. Specialists are
      associated with species' nutritional needs and their activation is known to be
      malleable by internal physiological conditions and contaminated external caloric
      sources. S specialists, associated with the heterodimeric G-protein coupled
      receptor T1R, and N specialists, associated with the epithelial sodium channel
      ENaC, are consistent with labeled line coding from taste bud to afferent neuron.
      Yet, S-specialist neurons and behavior are less specific than T1R2-3 in
      encompassing glutamate and E generalist neurons are much less specific than a
      candidate, PDK TRP channel, sour receptor in encompassing salts and bitter
      stimuli. Specialist labeled lines for nutrients and generalist patterns for
      aversive electrolytes may be transmitting taste information to the brain side by
      side. However, specific roles of generalists in taste quality coding may be
      resolved by selecting stimuli and stimulus levels found in natural situations.
      T2Rs, participating in reflexes via the glossopharynygeal nerve, became highly
      diversified in mammalian phylogenesis as they evolved to deal with dangerous
      substances within specific environmental niches. Establishing the information
      afferent neurons traffic to the brain about natural taste stimuli imbedded in
      dynamic complex mixtures will ultimately "crack taste codes."

PMID- 18824079
TI  - Remarkable neuronal hypoxia tolerance in the deep-diving adult hooded seal
      (Cystophora cristata).
AB  - Seals cope with regular exposure to diving hypoxia by storing oxygen in blood and
      skeletal muscles and by limiting the distribution of blood-borne oxygen to all
      but the most hypoxia vulnerable tissues (brain, heart), through dramatic
      cardiovascular adjustments. Still, arterial oxygen tension of freely diving seals
      regularly drops to levels that would be fatal to most non-diving mammals. Some
      cerebral protection is offered through diving-induced brain cooling and,
      possibly, enhanced oxygen delivery due to a particularly high brain capillary
      density. Here we test the hypothesis that seal neurons are in addition also
      intrinsically hypoxia tolerant. For this purpose we compared neuronal hypoxic
      responses in adult hooded seals and mice using intracellular recordings from the
      pyramidal layer of isolated visual cortex slices. Neurons from both species
      maintained normoxic membrane potentials of -60 to -70 mV, which in seals
      increased by only 13.4 +/- 19.2 mV (n = 7) during the first 10 min of severe
      hypoxia (oxygen content of saline perfusate reduced from approximately 75 to
      approximately 5%), while the corresponding depolarization of mouse neurons was
      significantly larger (65.0 +/- 44.9 mV; n = 14; p = 0.006). Mouse neurons
      moreover lost the ability to discharge after 5 +/- 2 min in hypoxia, while seal
      neurons continued on average for 19 +/- 10 min, in one case for a full hour.
      These results show that seal neocortical neurons exhibit a remarkable intrinsic
      hypoxia tolerance, which may partly explain why seals can dive for more than 1 h
      and stay alert without suffering from detrimental effects of hypoxia.

PMID- 18824080
TI  - Imidacloprid acts as an antagonist on insect nicotinic acetylcholine receptor
      containing the Y151M mutation.
AB  - Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels which
      mediate fast cholinergic synaptic transmission in insect and vertebrate nervous
      systems. A point mutation Y151S had been identified in Nilaparvata lugens (brown
      planthopper) that is associated with target-site resistance to neonicotinoid
      insecticides. Methionine (M151) is found in the Caenorhabditis elegans alpha
      subunit acr18 at the corresponding site to Y151 in Nlalpha1. Here, the Y151M
      mutation was introduced into Nlalpha1 and co-expressed with rat beta2 in Xenopus
      oocytes. The influence of the Y151M mutation on the affinity and efficacy of
      acetylcholine and imidacloprid on hybrid nAChRs Nla1/beta2 was examined by
      radioligand binding and electrophysiology methods. Imidacloprid bound with
      Nlalpha1(Y151M)/beta2 with high affinity, although this was lower than that of
      Nlalpha1/beta2. However, imidacloprid did not show agonist actions on
      Nlalpha1(Y151M)/beta2, although the quite small responses to imidacloprid at high
      concentrations (0.5-1.0 mM) were detected in some (but not all) oocytes
      expressing Nlalpha1(Y151M/beta2. Further study demonstrated that imidacloprid
      acted as an antagonist on Nlalpha1(Y151M)/beta2, which blocked responses to
      acetylcholine on Nlalpha1(Y151M)/beta2 with a pIC50 of 5.14 +/- 0.06.
      Nlalpha1(Y151M)/beta2 nAChRs block by imidacloprid was slowly reversible. This is
      the first time a point mutation in loop B of insect nAChR alpha subunits has been
      identified that changes the mode of interaction between neonicotinoid
      insecticides and insect nAChRs.

PMID- 18824081
TI  - Cocaine interacts with the novelty-seeking trait to modulate FGFR1 gene
      expression in the rat.
AB  - The present study sought to determine the interaction between the novelty-seeking
      trait and cocaine treatment on gene expression in the fibroblast growth factor
      (FGF) system. Specifically, we assessed the regulation of FGFR1 in response to
      cocaine in animals that were selectively bred on the basis of their locomotor
      response to a novel environment. High-responder (HR) rats are those that exhibit
      increased locomotor response and exploratory behavior in a novel environment and
      low-responder (LR) rats are those that exhibit lower levels of exploratory
      behavior and are less active. Both phenotypes received daily injections of either
      cocaine (15 mg/kg, i.p.) or saline for 7 consecutive days. Animals were
      sacrificed 45 min following their last injection and FGFR1 gene expression was
      assessed in the hippocampus and prefrontal cortex by mRNA in situ hybridization.
      HR-bred rats exhibited increased FGFR1 mRNA in the hippocampus compared to LR
      bred rats. Furthermore, cocaine decreased FGFR1 mRNA in the hippocampus and
      increased FGFR1 mRNA in the prefrontal cortex. Finally, HR and LR rats differed
      in their response to cocaine between brain regions. In the hippocampus, cocaine
      decreased gene expression in HR-bred rats without affecting LR-bred rats, whereas
      in the prefrontal cortex cocaine increased gene expression in LR-bred rats
      without affecting HR-bred rats. These results suggest that cocaine interacts with
      the novelty-seeking trait to alter gene expression. Thus, the FGF system may
      contribute to individual differences in the response to drugs of abuse.

PMID- 18824082
TI  - Aging stem cells and regenerative biomedicine: concepts, opportunities and
      technological advances.

PMID- 18824083
TI  - Supplemental nitric oxide augments satellite cell activity on cultured myofibers
      from aged mice.
AB  - Skeletal muscle regenerative potential is reduced with aging. We hypothesized
      that in vitro activation of muscle satellite cells would be compromised, and that
      nitric oxide (NO) supplementation would improve satellite cell activity in old
      muscle. Single intact myofibers were isolated from the gastrocnemius muscles of
      young (2 mo), adult (10 mo), and aged (22 mo) mice. Fibers were centrifuged to
      stimulate satellite cells and incubated with L-arginine (2mM), the NO donor,
      diethylenetriamine NONOate (DETA-NO; 10 microM), or control media for 48 h. The
      number of activated satellite cells after centrifugation was reduced in aged
      fibers compared to young and adult. L-arginine or DETA-NO treatment increased
      satellite cell activation in all age groups. However, an age-dependent deficit in
      satellite cell activity persisted within treatment groups. In separate fibers,
      exogenous HGF was equally effective in activating satellite cells across age
      groups, indicating that events downstream of HGF release are intact in aged
      muscle. These data suggest that l-arginine bioavailability and NO production
      limit muscle satellite cell activity in response to a submaximal mechanical
      stimulus, regardless of age. Further, the decline in satellite cell activity in
      early senescence can be partially abrogated by exogenous L-arginine or an NO
      donor.

PMID- 18824084
TI  - Inflammation and the neurovascular unit in the setting of focal cerebral
      ischemia.
AB  - Responses to focal cerebral ischemia by neurons and adjacent microvessels are
      rapid, simultaneous, and topographically related. Recent observations indicate
      the simultaneous appearance of proteases by components of nearby microvessels
      that are also expressed by neurons in the ischemic territory, implying that the
      events could be coordinated. The structural relationship of neurons to their
      microvascular supply, the direct functional participation of glial cells, and the
      observation of a highly ordered microvessel-neuron response to ischemia suggest
      that these elements are arranged in and behave in a unitary fashion, the
      neurovascular unit. Their roles as a unit in the stimulation of cellular
      inflammation and the generation of inflammatory mediators during focal cerebral
      ischemia have not been explored yet. However, components of the neurovascular
      unit both generate and respond to these influences under the conditions of
      ischemia. Here we briefly explore the potential inter-relationships of the
      components of the neurovascular unit with respect to their potential roles in
      ischemia-induced inflammatory responses.

PMID- 18824085
TI  - Expression of the GABA(A) receptor gamma4-subunit gene in discrete nuclei within
      the zebra finch song system.
AB  - The acquisition, production and maintenance of song by oscine birds is a form of
      audition-dependent learning that, in many ways, resembles the process by which
      humans learn to speak. In songbirds, the generation of structured song is
      determined by the activity of two interconnected neuronal pathways (the anterior
      forebrain pathway and the vocal motor pathway), each of which contains a number
      of discrete nuclei that together form the song system. It is becoming
      increasingly evident that inhibitory GABAergic mechanisms are indispensable in
      counterbalancing the excitatory actions of glutamate and, thus, likely shape the
      neuronal firing patterns of neurons within this network. Furthermore, there is
      compelling evidence for the involvement of GABA(A) receptors, although the
      molecular composition of these has, to date, remained elusive. Here we describe
      the isolation of a complementary DNA for the zebra finch GABA(A) receptor gamma4
      subunit, and map the expression pattern of the corresponding gene within the
      zebra finch (Taeniopygia guttata) brain. Our findings show, remarkably, that the
      gamma4-subunit transcript is highly enriched in the major nuclei of the song
      system, including the lateral magnocellular nucleus of the anterior nidopallium
      (LMAN), the medial magnocellular nucleus of the anterior nidopallium (MMAN), Area
      X, the robust nucleus of the arcopallium (RA) and the HVC (used as the proper
      name), as well as Field L, which innervates the area surrounding HVC. In summary,
      we have demonstrated the presence of the mRNA for the gamma4 subunit of the
      GABA(A) receptor, the major inhibitory receptor in brain, in most of the nuclei
      of the two neural circuits that mediate song production in the zebra finch. This
      not only marks the beginning of the characterization of the GABA(A) receptor
      subtype(s) that mediates the actions of GABA in the song system but it also
      provides a robust molecular marker with which to distinguish song system-specific
      brain structures.

PMID- 18824086
TI  - In vivo requirement of TGF-beta/GDNF cooperativity in mouse development: focus on
      the neurotrophic hypothesis.
AB  - Neurotrophic factors are well-recognized extracellular signaling molecules that
      regulate neuron development including neurite growth, survival and maturation of
      neuronal phenotypes in the central and peripheral nervous system. Previous
      studies have suggested that TGF-beta plays a key role in the regulation of neuron
      survival and death and potentiates the neurotrophic activity of several
      neurotrophic factors, most strikingly of GDNF. To test the physiological
      relevance of this finding, TGF-beta2/GDNF double mutant (d-ko) mice were
      generated. Double mutant mice die at birth like single mutants due to kidney
      agenesis (GDNF-/-) and congential cyanosis (TGF-beta2-/-), respectively. To test
      for the in vivo relevance of TGF-beta2/GDNF cooperativity to regulate neuron
      survival, mesencephalic dopaminergic neurons, lumbar motoneurons, as well as
      neurons of the lumbar dorsal root ganglion and the superior cervical ganglion
      were investigated. No loss of mesencephalic dopaminergic neurons was observed in
      double mutant mice at E18.5. A partial reduction in neuron numbers was observed
      in lumbar motoneurons, sensory and sympathetic neurons in GDNF single mutants,
      which was further reduced in TGF-beta2/GDNF double mutant mice at E18.5. However,
      TGF-beta2 single mutant mice showed no loss of neurons. These data point towards
      a cooperative role of TGF-beta2 and GDNF with regard to promotion of survival
      within the peripheral motor and sensory systems investigated.

PMID- 18824087
TI  - Cloning and functional characterization of the 5' regulatory region of ovine
      Hormone Sensitive Lipase (HSL) gene.
AB  - Hormone Sensitive Lipase (HSL) catalyzes the rate-limiting step in the
      mobilization of fatty acids from adipose tissue, thus determining the supply of
      energy substrates in the body. HSL enzymatic activity is increased by adrenergic
      agonists, such as catecholamines and glucagons, which induce cyclic AMP (cAMP)
      intracellular production, subsequently followed by the activation of Protein
      Kinase A (PKA) and its downstream signaling cascade reactions. HSL constitutes
      the critical enzyme in the modulation of lipid stores and the only component
      being subjected to hormonal control in terms of the recently identified Adipose
      Triglyceride Lipase (ATGL). In order to acquire detailed knowledge with regard to
      the mechanisms regulating ovine HSL (ovHSL) gene transcription activity, we
      initially isolated and cloned the 5' proximal and distal promoter regions through
      a genome walking approach, with the utilization of the already characterized
      ovHSL cDNAs. As evinced by BLAST analysis and a multiple alignment procedure, the
      isolated genomic fragment of 2.744 kb appeared to contain the already specified
      5'-untranslated region (5'-UTR), which was interrupted by a relatively large
      intron of 1.448 kb. Regarding the upstream remaining part of 1.224 kb, it was
      demonstrated to represent a TATA-less promoter area, harboring several cis
      regulatory elements that could be putatively recognized by relatively more
      general transcription factors, mainly including Stimulating protein 1 (Sp1),
      CCAAT-box Binding Factors (CBFs), Activator Protein 2 (AP2) and Glucocorticoid
      Receptor (GR), as well as other cis-acting regions denominated as Insulin
      Response Element (IRE), Glucose Response Element (GRE), Fat Specific Element
      (FSE) and cAMP Response Element (CRE), which could likely function in a
      nourishment (i.e. glucose)-/hormone-dependent fashion. When different genomic
      fragments were directionally (5' to 3') cloned into a suitable reporter vector
      upstream of a promoter-less luciferase gene and transiently transfected into 3T3
      L1 (mouse fibroblasts) as well as T24 (human bladder cancer) cell lines, strong
      promoter activities were unambiguously detected, with the -140/+18 nucleotide
      sequence bearing the highest transcriptional response, thus indicating that the
      1.224 kb 5' flanking region, isolated by genome walking, veritably contains the
      ovHSL gene promoter. Of particular significance are the observations that the
      functional promoter fragments could trigger the transcriptional activity of
      luciferase gene only under high concentration of glucose conditions in both cell
      lines.

PMID- 18824088
TI  - The transcriptional terminator sequences downstream of the covR gene terminate
      covR/S operon transcription to generate covR monocistronic transcripts in
      Streptococcus pyogenes.
AB  - CovR/S is an important two component regulatory system, which regulates about 15%
      of the gene expression in Streptococcus pyogenes. The covR/S locus was identified
      as an operon generating an RNA transcript around 2.5-kb in size. In this study,
      we found the covR/S operon produced three RNA transcripts (around 2.5-, 1.0-, and
      0.8-kb in size). Using RNA transcriptional terminator sequence prediction and
      transcriptional terminator analysis, we identified two atypical rho-independent
      terminator sequences downstream of the covR gene and showed these terminator
      sequences terminate RNA transcription efficiently. These results indicate that
      covR/S operon generates covR/S transcript and monocistronic covR transcripts.

PMID- 18824089
TI  - Systems based mapping demonstrates that recovery from alkylation damage requires
      DNA repair, RNA processing, and translation associated networks.
AB  - The identification of cellular responses to damage can promote mechanistic
      insight into stress signalling. We have screened a library of 3968 Escherichia
      coli gene-deletion mutants to identify 99 gene products that modulate the
      toxicity of the alkylating agent methyl methanesulfonate (MMS). We have developed
      an ontology mapping approach to identify functional categories over-represented
      with MMS-toxicity modulating proteins and demonstrate that, in addition to DNA re
      synthesis (replication, recombination, and repair), proteins involved in mRNA
      processing and translation influence viability after MMS damage. We have also
      mapped our MMS-toxicity modulating proteins onto an E. coli protein interactome
      and identified a sub-network consisting of 32 proteins functioning in DNA repair,
      mRNA processing, and translation. Clustering coefficient analysis identified
      seven highly connected MMS-toxicity modulating proteins associated with
      translation and mRNA processing, with the high connectivity suggestive of a
      coordinated response. Corresponding results from reporter assays support the idea
      that the SOS response is influenced by activities associated with the mRNA
      translation interface.

PMID- 18824090
TI  - Characterization, selection, and development of an orally dosed drug polymorph
      from an enantiotropically related system.
AB  - Solid-state characterization methods are used to study a dimorphic pharmaceutical
      compound and select a form for development. Polymorph screening found that [4-(4
      chloro-3-fluorophenyl)-2-[4-(methyloxy)phenyl]-1,3-thiazol-5-yl] acetic acid can
      crystallize into two non-solvated polymorphs designated Forms 1 and 2. Physical
      methods including vibrational spectroscopy, X-ray powder diffraction, solid-state
      NMR (SSNMR), thermal analysis, and gravimetric water vapor sorption are used to
      fully characterize the two polymorphs. Temperature-dependent competitive ripening
      experiments and solubility measurements indicated that the polymorphs in this
      system exhibit enantiotropy with a thermodynamic transition temperature of 35+/-3
      degrees C. This complicates the selection of a polymorph to progress in drug
      development. Both forms had undesirable qualities; however, a particular drawback
      of Form 1 was found in its tendency to convert to Form 2 upon milling. Combining
      this effect and the desired formulation approach with physical property results
      led to a rationale for the choice of Form 2 for further development. Because this
      form is thermodynamically metastable at room temperature, analytical approaches
      were developed to ensure its exclusive presence, including a quantitative
      infrared spectroscopic method for drug substance and (13)C and (19)F solid-state
      NMR limit tests for the undesired form in drug product at drug loads of 8.3%
      (w/w).

PMID- 18824091
TI  - Nrf2-induced antioxidant protection: a promising target to counteract ROS
      mediated damage in neurodegenerative disease?
AB  - Neurodegenerative diseases share various pathological features, such as
      accumulation of aberrant protein aggregates, microglial activation, and
      mitochondrial dysfunction. These pathological processes are associated with
      generation of reactive oxygen species (ROS), which cause oxidative stress and
      subsequent damage to essential molecules, such as lipids, proteins, and DNA.
      Hence, enhanced ROS production and oxidative injury play a cardinal role in the
      onset and progression of neurodegenerative disorders. To maintain a proper redox
      balance, the central nervous system is endowed with an antioxidant defense
      mechanism consisting of endogenous antioxidant enzymes. Expression of most
      antioxidant enzymes is tightly controlled by the antioxidant response element
      (ARE) and is activated by nuclear factor E2-related factor 2 (Nrf2). In past
      years reports have highlighted the protective effects of Nrf2 activation in
      reducing oxidative stress in both in vitro and in vivo models of
      neurodegenerative disorders. Here we provide an overview of the involvement of
      ROS-induced oxidative damage in Alzheimer's disease, Parkinson's disease, and
      Huntington's disease and we discuss the potential therapeutic effects of
      antioxidant enzymes and compounds that activate the Nrf2-ARE pathway.

PMID- 18824092
TI  - Effect of oral methyl-t-butyl ether (MTBE) on the male mouse reproductive tract
      and oxidative stress in liver.
AB  - MTBE is found in water supplies used for drinking and other purposes. These
      experiments follow up on earlier reports of reproductive tract alterations in
      male mice exposed orally to MTBE and explored oxidative stress as a mode of
      action. CD-1 mice were gavaged with 400-2000 mg/kg MTBE on days 1, 3, and 5,
      injected i.p. with hCG (2.5 IU/g) on day 6, and necropsied on day 7. No effect
      was seen in testis histology or testosterone levels. Using a similar dosing
      protocol, others had initially reported disruption of seminiferous tubules in
      MTBE-gavaged mice, although later conclusions published were consistent with our
      findings. Another group had also reported testicular and other reproductive
      system abnormalities in male BALB/c mice exposed for 28 days to 80-8000 microg/ml
      MTBE in drinking water. We gave these MTBE concentrations to adult mice for 28
      days and juvenile mice for 51 days through PND 77. Evidence of oxidative stress
      was examined in liver homogenates from the juvenile study using MDA, TEAC and
      8OH2hG as endpoints. MTBE exposures at the levels examined indicated no
      significant changes in the male mouse reproductive tract and no signs of hepatic
      oxidative stress. This appears to be the first oral MTBE exposure of juvenile
      animals, and also the first to examine potential for MTBE to cause oxidative
      stress in vivo using a typical route of human exposure.

PMID- 18824093
TI  - Mutation of cGMP phosphodiesterase 6alpha'-subunit gene causes progressive
      degeneration of cone photoreceptors in zebrafish.
AB  - In mammals, the blockade of the phototransduction cascade causes loss of vision
      and, in some cases, degeneration of photoreceptors. However, the molecular
      mechanisms that link phototransduction with photoreceptor degeneration remain to
      be elucidated. Here, we report that a mutation in the gene encoding a central
      effector of the phototransduction cascade, cGMP phosphodiesterase 6alpha'-subunit
      (PDE6alpha'), affects not only the vision but also the survival of cone
      photoreceptors in zebrafish. We isolated a zebrafish mutant, called eclipse
      (els), which shows no visual behavior such as optokinetic response (OKR). The
      cloning of the els mutant gene revealed that a missense mutation occurred in the
      pde6alpha' gene, resulting in a change in a conserved amino acid. The PDE6
      expressed in rod photoreceptors is a heterotetramer comprising two closely
      related similar hydrolytic alpha and beta subunits and two identical inhibitory
      gamma subunits, while the PDE6 expressed in cone photoreceptors consists of two
      homodimers of alpha' subunits, each with gamma subunits. The els mutant displays
      no visual response to bright light, where cones are active, but shows relatively
      normal OKR to dim light, where only rods function, suggesting that only the cone
      specific phototransduction pathway is disrupted in the els mutant. Furthermore,
      in the els mutant, cones are selectively eliminated but rods are retained at the
      adult stage, suggesting that cones undergo a progressive degeneration in the els
      mutant retinas. Taken together, these data suggest that PDE6alpha' activity is
      important for the survival of cones in zebrafish.

PMID- 18824094
TI  - The octarepeat region of prion protein, but not the TM1 domain, is important for
      the antioxidant effect of prion protein.
AB  - The cellular prion protein (PrP(c)) plays a crucial role in the pathogenesis of
      prion diseases, but its physiological function is far from understood. Several
      candidate functions have been proposed including binding and internalization of
      metal ions, a superoxide dismutase-like activity, regulation of cellular
      antioxidant activities, and signal transduction. The transmembrane (TM1) region
      of PrP(c) (residues 110-135) is particularly interesting because of its very high
      evolutionary conservation. We investigated a possible role of TM1 in the
      antioxidant defense, by assessing the impact of overexpressing wt-PrP or deletion
      mutants in N(2)A mouse neuroblastoma cells on intracellular reactive oxygen
      species (ROS) levels. Under conditions of oxidative stress, intracellular ROS
      levels were significantly lowered in cells overexpressing either wild-type PrP(c)
      (wt-PrP) or a deletion mutant affecting TM1 (Delta8TM1-PrP), but, as expected,
      not in cultures overexpressing a deletion mutant lacking the octapeptide region
      (Deltaocta-PrP). Overexpression of wt-PrP, Delta8TM1-PrP, or Deltaocta-PrP did
      not affect basal ROS levels. Interestingly, the mitochondrial membrane potential
      was significantly lowered in Deltaocta-PrP-transfected cultures in the absence of
      oxidative stress. We conclude that the protective effect of PrP(c) against
      oxidative stress involves the octarepeat region but not the TM1 domain nor the
      high-affinity copper binding site described for human residues His96/His111.

PMID- 18824095
TI  - In vitro and cell uptake studies for targeting of ligand anchored nanoparticles
      for colon tumors.
AB  - Hyaluronic acid (HA) coupled chitosan nanoparticles (HACTNP) bearing 5
      flurouracil (5FU) were prepared, by ionotropic gelation method, for the effective
      delivery of drug to the colon tumors. HACTNP appeared to be spherical in shape
      and mean size was found to be around 150+/-3.4nm with low polydispersity index.
      The in vitro drug release was investigated using USP dissolution test (paddle
      type) apparatus in different simulated GIT fluids. The biocompatibility of NPs
      formulations were evaluated for in vitro cytotoxicity by MTT assay using HT-29
      cell lines and cell uptake was assessed by fluorescent microscopy. Cellular
      uptake of HACTNP was determined by incorporating calcein as a fluorescent marker.
      The cellular uptake of fluorescent HACTNP was clearly evidenced by fluorescence
      microscopy. HACTNP nanoparticles showed significant higher uptake by cancer cells
      as compared to uncoupled nanoparticles and the uptake of HA coupled CTNPs by HT
      29 colon cancer cells were observed to be 7.9 times more as compared to uncoupled
      CTNPs at the end of 4h. The cytotoxicity of 5FU incorporated in HACTNP was higher
      compared to the conventional 5FU solution, even at the lower concentrations. 5FU
      in HACTNP was about 2.60-folds more effective than free 5FU on HT-29 cells.

PMID- 18824096
TI  - Intraorally fast-dissolving particles of a poorly soluble drug: preparation and
      in vitro characterization.
AB  - In this study, the dissolution rate of a poorly soluble drug, perphenazine (PPZ)
      was improved by a solid dispersion technique to permit its usage in intraoral
      formulations. Dissolution of PPZ (4 mg) in a small liquid volume (3 ml, pH 6.8)
      within one minute was set as the objective. PVP K30 and PEG 8000 were selected
      for carriers according to the solubility parameter approach and their 5/1, 1/5
      and 1/20 mixtures with PPZ (PPZ/polymer w/w) were prepared by freeze-drying from
      0.1 N HCl solutions. The dissolution rate of PPZ was improved with all
      drug/polymer mixture ratios compared to crystalline or micronized PPZ. A major
      dissolution rate improvement was seen with 1/5 PPZ/PEG formulation, i.e. PPZ was
      dissolved completely within one minute. SAXS, DSC and XRPD measurements indicated
      that solid solutions of amorphous PPZ in amorphous PVP or in partly amorphous PEG
      were formed. DSC and FTIR studies suggested that PPZ dihydrochloride salt was
      formed and hydrogen bonding was occurred between PPZ and the polymers. It was
      concluded that molecular mixing together with salt formation promoted the
      dissolution of PPZ, especially in the case of the 1/5 PPZ/PEG dispersion, making
      it a promising candidate for use in intraoral formulations.

PMID- 18824097
TI  - Lipid nanoparticles for parenteral delivery of actives.
AB  - The present review compiles the applications of lipid nanoparticles mainly solid
      lipid nanoparticles (SLN), nanostructured lipid carriers (NLC) and lipid drug
      conjugates (LDC) in parenteral delivery of pharmaceutical actives. The attempts
      to incorporate anticancer agents, imaging agents, antiparasitics, antiarthritics,
      genes for transfection, agents for liver, cardiovascular and central nervous
      system targeting have been summarized. The utility of lipid nanoparticles as
      adjuvant has been discussed separately. A special focus of this review is on
      toxicity caused by these kinds of lipid nanoparticles with a glance on the fate
      of lipid nanoparticles after their parenteral delivery in vivo viz the protein
      adsorption patterns.

PMID- 18824098
TI  - Characterisation and phylogenetic relationships of Anisogramma virgultorum and A.
      anomala in the Diaporthales (Ascomycota).
AB  - The two diaporthalean fungi Anisogramma virgultorum and A. anomala are biotrophic
      parasites. A. virgultorum causes stromatal cankers on young shoots of birch
      whereas A. anomala infects young branches of Corylus avellana. Although previous
      classifications based on morphological characteristics placed both species in the
      Gnomoniaceae, Diaporthales, their taxonomic position within the order and their
      relationship to each other required further clarification. We determined the
      nucleotide sequences of the ITS and partial LSU nu-rDNA regions of both species.
      A putative second teleomorph form of A. virgultorum, described in the literature
      as the 'single perithecial form', was also included in the analysis. Based on
      phylogenetic analyses of LSU sequences, the stromatal forms of A. virgultorum and
      A. anomala were part of a well-supported monophyletic sister clade to the
      Gnomoniaceae. The single perithecial form was placed within a clade containing
      representative members of the Gnomoniaceae, separate from species of Anisogramma.
      These results indicate that the single perithecial form of A. virgultorum
      actually represents an unrelated and as yet unidentified species of Gnomoniaceae.
      A morphological description of asci and ascospores of the three species is given.
      A Wilcoxon two sample test revealed that asci of the stromatal form of A.
      virgultorum were significantly shorter than those of the single perithecial
      species. Ascospores of the stromatal form of A. virgultorum were significantly
      shorter and wider than those of the single perithecial species.

PMID- 18824099
TI  - Sensory neuron voltage-gated sodium channels as analgesic drug targets.
AB  - Voltage-gated sodium channels are crucial determinants of neuronal excitability
      and signalling; some specific channel subtypes have been implicated in a number
      of chronic pain conditions. Human genetic studies show gain-of-function or loss
      of-function mutations in Na(V)1.7 lead to an enhancement or lack of pain,
      respectively, whilst transgenic mouse and knockdown studies have implicated
      Na(V)1.3, Na(V)1.8 and Na(V)1.9 in peripheral pain pathways. The development of
      subtype-specific sodium channel blockers, though clearly desirable, has been
      technically challenging. Recent advances exploiting both natural products and
      small molecule selective channel blockers have demonstrated that this approach to
      pain control is feasible. These observations provide a rationale for the
      development of new analgesics without the side effect profile of broad spectrum
      sodium channel blockers.

PMID- 18824100
TI  - Music perception, pitch, and the auditory system.
AB  - The perception of music depends on many culture-specific factors, but is also
      constrained by properties of the auditory system. This has been best
      characterized for those aspects of music that involve pitch. Pitch sequences are
      heard in terms of relative as well as absolute pitch. Pitch combinations give
      rise to emergent properties not present in the component notes. In this review we
      discuss the basic auditory mechanisms contributing to these and other perceptual
      effects in music.

PMID- 18824102
TI  - Measuring smells.
AB  - Olfaction consists of a set of transforms from a physical space of odorant
      molecules, through a neural space of information processing, and into a
      perceptual space of smell. Elucidating the rules governing these transforms
      depends on establishing valid metrics for each of the three spaces. Here we first
      briefly review the perceptual and neural spaces, and then concentrate on the
      physical space of odorant molecules. We argue that the lack of an agreed-upon
      odor metric poses a significant obstacle toward understanding the neurobiology of
      olfaction, and suggest two alternative odor metrics as possible solutions.

PMID- 18824101
TI  - Hair cell afferent synapses.
AB  - This review will cover advances in the study of hair cell afferent synaptic
      function occurring between 2005 and 2008. During this time, capacitance
      measurements of vesicular fusion have continued to be refined, optical methods
      have added insights regarding vesicle trafficking, and paired intracellular
      recordings have established the transfer function of the afferent synapse at high
      resolution. Further, genes have been identified with forms of deafness known as
      auditory neuropathy, and their role in afferent signaling explored in mouse
      models. With these advances, our view of the hair cell afferent synapse has
      continued to be refined, and surprising properties have been revealed that
      emphasize the unique role of this structure in neural function.

PMID- 18824103
TI  - Development of an early biomarker for the ovarian liability of selective estrogen
      receptor modulators in rats.
AB  - Selective estrogen receptor modulators (SERMs) have the potential to treat
      estrogen sensitive diseases such as uterine leiomyoma and endometriosis, which
      are prevalent in reproductive age women. However, SERMs also increase the risk of
      developing ovarian cysts in this population, a phenomenon that is not seen in
      postmenopausal women. It is believed that current SERMs partially block
      estradiol's ability to downregulate gonadotropin-releasing hormone (GnRH)
      secretion from the hypothalamus thereby interfering with estradiol's negative
      feedback, leading to increased ovarian stimulation by gonadotropins, and cyst
      formation. It has been postulated that a SERM with poor brain exposure would have
      less negative effect on the HPO axis, therefore reducing the risk of developing
      ovarian cysts. In order to test this hypothesis, we identified an early marker of
      SERM-dependent ovarian effects: upregulation of Cyp17a1 mRNA. SERMs known to
      cause ovarian cysts upregulate Cyp17a1 after only 4 days of dosing and
      suppression of the HPO axis prevented this regulation, indicating that ovarian
      expression of Cyp17a1 was secondary to SERM's effect on the brain. We then
      characterized three SERMs with similar binding affinity and antagonist effects on
      the uterus for their relative brain/plasma exposure and ovarian effects. We found
      that the degree of brain exposure correlated very well with Cyp17a1 expression.

PMID- 18824104
TI  - A novel SNP in a vitamin D response element of the CYP24A1 promoter reduces
      protein binding, transactivation, and gene expression.
AB  - The active form of vitamin D (1alpha,25(OH)(2)D(3)) is known to have
      antiproliferative effects and has been implicated in cancers of the colon,
      breast, and prostate. These cancers occur more frequently among African Americans
      than Caucasians, and individuals with African ancestry are known to have
      approximately twofold lower levels of serum vitamin D (25(OH)D) compared with
      individuals of European ancestry. However, epidemiological studies of the vitamin
      D receptor (VDR) have shown inconsistent associations with cancer risk,
      suggesting that differences in other genes in the pathway may be important. We
      sought to identify functionally significant polymorphic variants in CYP24A1, a
      gene that is highly inducible by 1alpha,25(OH)(2)D(3) and that encodes the
      primary catabolic enzyme in the pathway. Here we report the identification of six
      novel SNPs in the human CYP24A1 promoter, including one at nucleotide -279
      occurring within the distal vitamin D response element (VDRE2). Our experiments
      demonstrate that the VDRE2 variant results in decreased protein binding and
      transactivation in vitro, and reduced expression of CYP24A1 in cultured primary
      human lymphocytes provides evidence for an effect in vivo. This variant was only
      observed in our African American population, and represents a first step toward
      understanding differences in disease risk among racial/ethnic groups.

PMID- 18824105
TI  - Purification, refolding and autoactivation of the recombinant cysteine proteinase
      EhCP112 from Entamoeba histolytica.
AB  - The cysteine proteinase EhCP112 and the adhesin EhADH112 assemble to form the
      EhCPADH complex involved in Entamoeba histolytica virulence. To further
      characterize this cysteine proteinase, the recombinant full-length EhCP112 enzyme
      was expressed and purified under denaturing conditions. After a refolding step
      under reductive conditions, the inactive precursor (ppEhCP112) was processed to a
      35.5 kDa mature and active enzyme (EhCP112). The thiol specific inhibitor E-64,
      but not serine or aspartic proteinase inhibitors arrested this activation
      process. The activation step of the proenzyme followed by the mature enzyme
      suggests an autocatalytic process during EhCP112 maturation. The experimentally
      determined processing sites observed during EhCP112 activation lie close to
      processing sites of other cysteine proteinases from parasites. The kinetic
      parameters of the mature EhCP112 were determined using hemoglobin and azocasein
      as substrates. The proteinase activity of EhCP112 was completely inhibited by
      thiol inhibitors, E-64, TLCK, and chymostatin, but not by general proteinase
      inhibitors. Since EhCP112 is a proteinase involved in the virulence of E.
      histolytica, a reliable source of active EhCP112 is a key step for its
      biochemical characterization and to carry out future protein structure-function
      studies.

PMID- 18824106
TI  - Purification and partial characterization of the xanthine-uric acid transporter
      (UapA) of Aspergillus nidulans.
AB  - UapA, the uric acid-xanthine permease from the filamentous ascomycete Aspergillus
      nidulans, is one of the most thoroughly characterized purine/H(+) transporters in
      eukaryotes. Detailed studies have addressed its regulation of expression, at both
      the transcriptional and post-translational levels, in response to physiological
      and developmental signals. An extensive kinetic profile towards a plethora of
      purines and mutational analyses have established models on how UapA recognizes
      the purine ring and revealed specific amino acid residues involved in proper
      folding, topogenesis, function and specificity. The present work describes for
      the first time the purification of the UapA transporter of A. nidulans through
      overexpression via the strong, ethanol-inducible, glucose-repressible, alcA
      promoter. Purification, almost to homogeneity, was achieved by Ni(2+) affinity
      chromatography using a functional His-tagged UapA protein version. It is
      subsequently shown, by Circular Dichroism (CD) spectroscopy, that the purified
      protein is structured with a high alpha-helical content, as expected from the in
      silico predictions. The result of this work opens the way for further, analytical
      and biochemical studies on UapA at the protein level.

PMID- 18824107
TI  - Expression and functional characterization of the plant antimicrobial snakin-1
      and defensin recombinant proteins.
AB  - In this study, for the first time, functionally active, recombinant, cysteine
      rich plant proteins snakin-1 (SN1) and defensin (PTH1) were expressed and
      purified using a prokaryotic expression system. The overall level of
      antimicrobial activities of SN1 and PTH1 produced in Escherichia coli was
      commensurate with that of the same proteins previously obtained from plant
      tissues. Both proteins exhibited strong antibacterial activity against the
      phytopathogenic bacterium Clavibacter michiganensis subsp. sepedonicus (50%
      inhibitory concentration (IC(50)) 1.5-8 microM) and antifungal activity against
      the phytopathogenic fungi Colletotrichum coccoides and Botrytis cinerea (IC(50) 5
      14 microM). Significantly weaker activity was observed against Pseudomonas
      syringae pv. syringae and Pseudomonas syringae pv. tabaci. A pronounced
      synergistic antimicrobial effect against P. syringae pv. syringae and an additive
      effect against P. syringae pv. tabaci occurred with a combination of SN1 and
      PTH1. Aggregation of C. michiganensis subsp. sepedonicus bacterial cells at all
      protein concentrations tested was observed with the combination of SN1 and PTH1
      and with SN1 alone. Our results demonstrate the use of a cost effective
      prokaryotic expression system for generation and in vitro characterization of
      plant cysteine-rich proteins with potential antimicrobial activities against a
      wide range of phytopathogenic microorganisms in order to select the most
      effective agents for future in vivo studies.

PMID- 18824108
TI  - Cloning and expression analysis of two alternative splicing toll-like receptor 9
      isoforms A and B in large yellow croaker, Pseudosciaena crocea.
AB  - Toll-like receptors (TLRs) are the archetypal pattern-recognition receptors in
      sensing foreign pathogens. In this report, two alternative splicing isoforms of
      TLR9 (named PcTLR9A and PcTLR9B) cDNA were cloned from the large yellow croaker,
      Pseudosciaena crocea. The full-length cDNA of PcTLR9A was of 3637bp, including a
      5'-terminal untranslated region (UTR) of 111bp, 3'-terminal UTR of 355bp and an
      open reading frame (ORF) of 3171bp encoding a polypeptide of 1056 amino acids.
      However, the full-length cDNA of PcTLR9B was 119bp longer than that of PcTLR9A
      from the position of 3079-3197bp, which encoded a polypeptide of 1006 amino
      acids. Both of the PcTLR9A and PcTLR9B contained 12 typical structures of leucine
      rich repeats (LRRs), an LRRTYP and an LRRCT in the extracellular region and a
      conservative Toll/IL-1R (TIR) domain in the intracellular region. However,
      compared to PcTLR9A, conservative Box 3 was absent in PcTLR9B TIR domain.
      Quantitative real-time reverse transcription PCR analysis revealed a broad
      expression of PcTLR9A and PcTLR9B with the highest expression in spleen and the
      weakest expression in muscle. Expression of PcTLR9A and PcTLR9B after stimulation
      with formalin-inactivated Gram-negative bacterium Vibrio parahaemolyticus was
      tested in blood, spleen and liver. This indicated that the highest expression was
      3.3 times (at 24h) as much as that in the control in the spleen (p<0.05) and the
      lowest expression of PcTLR9A was 1/4 times (at 3h) of that in the control in the
      liver (p<0.05). PcTLR9B showed a similar expression pattern to PcTLR9A post
      injection. These results suggested that both PcTLR9A and PcTLR9B might play an
      important role in large yellow croaker defense against pathogenic infection.

PMID- 18824109
TI  - Allelic discrimination, three-dimensional analysis and gene expression of
      multiple transferrin alleles of common carp (Cyprinus carpio L.).
AB  - We cloned and sequenced four different transferrin (Tf) alleles (C, D, F and G)
      of European common carp (Cyprinus carpio carpio L.) and studied allelic diversity
      with respect to differences in sequence, constitutive transcription and three
      dimensional structure. Most of the disulfide bonds were conserved between human
      and carp Tf, and modeling confirmed the overall conservation of the three
      dimensional structure of carp Tf. While the iron-binding sites in the C-lobe of
      carp Tf were completely conserved, in the N-lobe the majority of iron
      coordinating residues were not conserved. This may have a serious impact on the
      ability of carp Tf to bind iron with both the C- and N-lobe. In contrast to human
      Tf, we could not detect potential N-glycosylation sites in carp Tf, which does
      not seem to be a glycoprotein. Comparison of the cDNA of the four Tf alleles of
      carp indicated 21 polymorphic sites of which 13 resulted in non-synonymous
      changes. Allelic diversity did not seem to influence the overall conservation of
      carp Tf. Neither the iron binding sites nor the receptor binding of carp Tf
      seemed influenced by allelic diversity. Possibly, interaction with pathogen
      associated receptors for Tf could be influenced by allelic diversity. Basal gene
      expression of Tf alleles D and G was especially high in carp liver. Although we
      could detect a higher transcription level of allele D than of Tf allele G in head
      kidney, thymus and spleen, the differences seem minor with respect to the very
      high transcription level in liver. Preliminary results with Tf-typed serum
      suggest a difference in the ability of Tf alleles D and G to modulate LPS-induced
      NO production in carp macrophages.

PMID- 18824110
TI  - Phylogeography of the bark beetle Dendroctonus mexicanus Hopkins (Coleoptera:
      Curculionidae: Scolytinae).
AB  - Dendroctonus mexicanus is polyphagous within the Pinus genus and has a wide
      geographical distribution in Mexico and Guatemala. We examined the pattern of
      genetic variation across the range of this species to explore its demographic
      history and its phylogeographic pattern. Analysis of the mtDNA sequences of 173
      individuals from 25 Mexican populations allowed to us identify 53 geographically
      structured haplotypes. High haplotype and low nucleotide diversities and Tajima's
      D indicate that D. mexicanus experienced rapid population expansion during its
      dispersal across mountain systems within its current range. The nested clade
      phylogeographic analysis indicates that the phylogeographic pattern of D.
      mexicanus is explained by continuous dispersion among lineages from the Sierra
      Madre Occidental, the Sierra Madre Oriental and the Trans-Mexican Volcanic Belt.
      However, we also observed isolation events among haplotypes from the Cofre de
      Perote/Trans-Mexican Volcanic Belt/Sierra Madre Oriental and the Trans-Mexican
      Volcanic Belt/Sierra Madre del Sur, which is consistent with the present
      conformation of mountain systems in Mexico and the emergence of geographical
      barriers during the Pleistocene.

PMID- 18824111
TI  - Phylogenetic relationships of Ruteae (Rutaceae): new evidence from the
      chloroplast genome and comparisons with non-molecular data.
AB  - Phylogenetic analyses of three cpDNA markers (matK, rpl16, and trnL-trnF) were
      performed to evaluate previous treatments of Ruteae based on morphology and
      phytochemistry that contradicted each other, especially regarding the taxonomic
      status of Haplophyllum and Dictamnus. Trees derived from morphological,
      phytochemical, and molecular datasets of Ruteae were then compared to look for
      possible patterns of agreement among them. Furthermore, non-molecular characters
      were mapped on the molecular phylogeny to identify uniquely derived states and
      patterns of homoplasy in the morphological and phytochemical datasets. The
      phylogenetic analyses determined that Haplophyllum and Ruta form reciprocally
      exclusive monophyletic groups and that Dictamnus is not closely related to the
      other genera of Ruteae. The different types of datasets were partly incongruent
      with each other. The discordant phylogenetic patterns between the phytochemical
      and molecular trees might be best explained in terms of convergence in secondary
      chemical compounds. Finally, only a few non-molecular synapomorphies provided
      support for the clades of the molecular tree, while most of the morphological
      characters traditionally used for taxonomic purposes were found to be
      homoplasious. Within the context of the phylogenetic relationships supported by
      molecular data, Ruta, the type genus for the family, can only be diagnosed by
      using a combination of plesiomorphic, homoplasious, and autapomorphic
      morphological character states.

PMID- 18824112
TI  - Phylogenetic analysis of Allium subg. Melanocrommyum infers cryptic species and
      demands a new sectional classification.
AB  - Allium subgenus Melanocrommyum (Alliaceae) from Eurasia comprises about 150
      mostly diploid species adapted to arid conditions. The group is taxonomically
      complicated with different and contradictory taxonomic treatments, and was
      thought to include a considerable number of hybrid species, as the taxa show an
      admixture of assumed morphological key characters. We studied the phylogeny of
      the subgenus, covering all existing taxonomic groups and their entire geographic
      distribution. We analyzed sequences of the nuclear rDNA internal transcribed
      spacer region (ITS) for multiple individuals of more than 100 species.
      Phylogenetic analyses of cloned and directly sequenced PCR products confirmed the
      monophyly of the subgenus, while most sections were either para- or polyphyletic.
      The splits of the large sections are supported by differences in the anatomy of
      flower nectaries. ITS data (i) demand a new treatment at sectional level, (ii) do
      not support the hypotheses of frequent gene flow among species, (iii) indicate
      that multiple rapid radiations occurred within different monophyletic groups of
      the subgenus, and (iv) detected separately evolving lineages within three
      morphologically clearly defined species (cryptic species). In two cases these
      lineages were close relatives, while in Allium darwasicum they fall in quite
      different clades in the phylogenetic tree. Fingerprint markers show that this
      result is not due to ongoing introgression of rDNA (ITS capture) but that genome
      wide differences between both lineages exist. Thus, we report one of the rare
      cases in plants where morphologically indistinguishable diploid species occurring
      in mixed populations are non-sister cryptic species.

PMID- 18824113
TI  - Divergent evolution of the thiolase superfamily and chalcone synthase family.
AB  - Enzymes of the thiolase superfamily catalyze the formation of carbon-carbon bond
      via the Claisen condensation reaction. Thiolases catalyze the reversible non
      decarboxylative condensation of acetoacetyl-CoA from two molecules of acetyl-CoA,
      and possess a conserved Cys-His catalytic diad. Elongation enzymes (beta-ketoacyl
      acyl carrier protein synthase (KAS) I and KAS II and the condensing domain of
      polyketide synthase) have invariant Cys and two His residues (CHH triad), while a
      Cys-His-Asn (CHN) triad is found in initiation enzymes (KAS III, 3-ketoacyl-CoA
      synthase (KCS) and the chalcone synthase (CHS) family). These enzymes all
      catalyze decarboxylative condensation reactions. 3-Hydroxyl-3-methylglutaryl-CoA
      synthase (HMGS) also contains the CHN triad, although it catalyzes a non
      decarboxylative condensation. That the enzymes of the thiolase superfamily share
      overall similarity in protein structure and function suggested a common
      evolutionary origin. All thiolases were found to have, in addition to the Cys-His
      diad, either Asn or His (thus C(N/H)H) at a position corresponding to the His in
      the CHH and CHN triads. In our phylogenetic analyses, the thiolase superfamily
      was divided into four main clusters according to active site architecture. During
      the functional divergence of the superfamily, the active architecture was
      suggested to evolve from the C(H)H in archaeal thiolases to the C(N/H)H in non
      archaeal thiolases, and subsequently to the CHH in the elongation enzymes and the
      CHN in the initiation enzymes. Based on these observations and available
      biochemical and structural evidences, a plausible evolutionary history for the
      thiolase superfamily is proposed that includes the emergence of decarboxylative
      condensing enzymes accompanied by a recruitment of the His in the CHH and CHN
      triads for a catalytic role during decarboxylative condensation. In addition,
      phylogenetic analysis of the plant CHS family showed separate clustering of CHS
      and non-CHS members of the family with a few exceptions, suggesting repeated gene
      birth-and-death and re-invention of non-CHS functions throughout the evolution of
      angiosperms. Based on these observations, predictions on the enzymatic functions
      are made for several members of the CHS family whose functions are yet to be
      characterized. Further, a moss CHS-like enzyme that is functionally similar to a
      cyanobacterial enzyme was identified as the most recent common ancestor to the
      plant CHS family.

PMID- 18824114
TI  - Translating insights from development into regenerative medicine: the function of
      Wnts in bone biology.
AB  - The Wnt pathway constitutes one of the most attractive candidates for modulating
      skeletal tissue regeneration based on its functions during skeletal development
      and homeostasis. Wnts participate in every stage of skeletogenesis, from the self
      renewal and proliferation of skeletal stem cells to the specification of
      osteochondroprogenitor cells and the maturation of chondrocytes and osteoblasts.
      We propose that the function of Wnts depend upon a skeletogenic cell's state of
      differentiation. In this review we summarize recent data with a focus on the
      roles of Wnt signaling in mesenchymal stem cell fate, osteoprogenitor cell
      differentiation, chondrocyte maturation, bone remodeling, and bone regeneration.

PMID- 18824115
TI  - Chromatin and Arabidopsis root development.
AB  - During development cells transit through different states as they pass from stem
      cell to terminally differentiated cell. There is evidence that the transition
      from one state to another can be accompanied by changes in epigenetic state of
      genes, which is embodied in chromatin state. Here we give an overview of the
      changes in chromatin that accompany the regulation of expression and review the
      evidence for the involvement of such changes during epidermal root development
      and discuss the roles that these changes play in the differentiation of the cell
      types involved.

PMID- 18824116
TI  - Posterior parietal cortex as part of a neural network for directed attention in
      rats.
AB  - A rodent model of directed attention has been developed based upon behavioral
      analysis of contralateral neglect, pharmacological manipulations, and anatomical
      analysis of neural circuitry. In each of these three domains the rodent model
      exhibits striking similarities to humans. We hypothesize that there is a specific
      thalamo-cortical-basal ganglia network that subserves spatial attentional
      functions. Key components of this network are medial agranular and posterior
      parietal cortex, dorsocentral striatum, and the lateral posterior thalamic
      nucleus. Several issues need to be addressed before we can hope to realistically
      understand or model the functions of this network. Among these are the roles of
      medial versus lateral posterior parietal cortex; cholinergic mechanisms in
      attention; interhemispheric interactions; the role of synchronous firing at the
      cortical, striatal, and thalamic levels; interactions between cortical and
      thalamic projections to the striatum; interactions between cortical and nigral
      inputs to the thalamus; the role of collicular inputs to the lateral posterior
      thalamic nucleus; the role of cerebral cortex versus superior colliculus in
      driving the motor output expressed as orienting behavior during directed
      attention; the extent to which the circuitry we describe for directed attention
      also plays a role in other forms of attention.

PMID- 18824117
TI  - Identification, characterization and expression of sex-related genes in testes of
      the giant tiger shrimp Penaeus monodon.
AB  - Isolation and characterization of genes involving gonadal development are an
      initial step towards understanding reproductive maturation and sex determination
      of the giant tiger shrimp (Penaeus monodon). In the present study, 896 clones
      from the testis cDNA library were sequenced. A total of 606 ESTs (67.6%)
      significantly matched sequences in the GenBank (E-value <1e-04) whereas 290 ESTs
      (32.4%) were newly unidentified transcripts. The full length cDNA of genes
      functionally involved in testicular development including cyclophilin A (PMCYA),
      small ubiquitin-like modifier 1 (PMSUMO-1), ubiquitin conjugating enzyme E2,
      dynactin subunit 5, cell division cycle 2 (cdc2) and mitotic checkpoint BUB3 were
      discovered. In addition, Tra-2, a gene involving sex determination cascades, was
      successfully characterized by RACE-PCR and first reported in crustaceans.
      Expression analysis indicated that a homologue of low molecular weight
      neurofilament protein XNF-L (termed P. monodon testis-specific transcript 1,
      PMTST1; N=8 for each sex) was only expressed in testes but not ovaries. PMCYA,
      thyroid hormone receptor-associated protein complex 240 kDa component (Trap240),
      multiple inositol polyphosphate phosphatase 2 (MIPP2) and heat shock-related 70
      kDa protein 2 (HSP70-2), but not PMSUMO-1, PMTra-2 and prohibitin2 were
      differentially expressed between ovaries and testes of P. monodon. Expression of
      PMTST1 was up-regulated but that of the remaining genes in testes of P. monodon
      broodstock was down-regulated after shrimp were molted (P<0.05). Significant
      reduction of PMSUMO-1 and increment of prohibitin2 transcripts in domesticated
      broodstock (P<0.05) suggested that these reproductively related genes may be used
      as biomarkers to evaluate reduced degrees of the reproductive maturation in
      domesticated P. monodon.

PMID- 18824118
TI  - Integrative and genomics approaches to uncover the mechanistic bases of fish
      behavior and its diversity.
AB  - Understanding the molecular mechanisms underlying fish behavior is of fundamental
      importance to further our understanding of the proximate and ultimate causes of
      variation in this trait and informs us on issues of animal husbandry,
      conservation, and welfare. One way to approach this question is to study
      variation in gene expression in individuals exhibiting different behaviors and
      relating it to variations at other phenotypic levels in an organismic, ecological
      and evolutionary context. Here we review studies that have shown that the use of
      such an integrative and genomics approach is greatly useful for shedding new
      light on the mechanisms of behaviors as diverse as social dominance, mate choice,
      reproduction and migration. We present studies that use functional genomics tools
      and integrate several biological levels of organization, including transcription
      variation, which are important in the context of integrative biology and genomics
      of fish behavior. We review studies of phenotype-level variation in transcription
      but also studies that focus on variation at the individual-level. Dissecting the
      molecular bases of among-individual variation in behavior, including the study of
      variation in temperament (behavioral syndrome/coping style) within and among
      populations, will gain importance in the field in the years to come.

PMID- 18824119
TI  - Effective lead selection for improved protein production in Aspergillus niger
      based on integrated genomics.
AB  - The filamentous fungus Aspergillus niger is widely exploited for industrial
      production of enzymes and organic acids. An integrated genomics approach was
      developed to determine cellular responses of A. niger to protein production in
      well-controlled fermentations. Different protein extraction methods in
      combination with automated sample processing and protein identification allowed
      quantitative analysis of 898 proteins. Three different enzyme overproducing
      strains were compared to their isogenic fungal host strains. Clear differences in
      response to the amount and nature of the overproduced enzymes were observed. The
      corresponding genes of the differentially expressed proteins were studied using
      transcriptomics. Genes that were up-regulated both at the proteome and
      transcriptome level were selected as leads for generic strain improvement. Up
      regulated proteins included proteins involved in carbon and nitrogen metabolism
      as well as (oxidative) stress response, and proteins involved in protein folding
      and endoplasmic reticulum-associated degradation (ERAD). Reduction of protein
      degradation through the removal of the ERAD factor doaA combined with
      overexpression of the oligosaccharyl transferase sttC in A. niger overproducing
      beta-glucuronidase (GUS) strains indeed resulted in a small increase in GUS
      expression.

PMID- 18824120
TI  - Effects of selected neuropeptides, mating status and castration on male
      reproductive tract movements and immunolocalization of neuropeptides in earwigs.
AB  - In earwigs, the male reproductive system is complex, comprising accessory glands
      and long dual intromittent organs for transfer of materials to the female and for
      removal of rival sperm. We investigated potential factors altering contractions
      of the male reproductive tracts in vitro. Tracts from 0-day (newly emerged) males
      displayed relatively little motility in vitro; however, those from 5-day
      (intermediate stage of sexual maturity) and 8-day (fully mature) males pulsed
      vigorously. Both 1 and 100 nM proctolin (RYLPT-OH) stimulated the rate of
      contraction of reproductive tracts from both 5-day and 8-day males. In contrast,
      1 nM and 100 nM FGLa AST (cockroach allatostatin) did not affect pulsations.
      However, 10 microM FGLa AST decreased activity of reproductive tracts. Mating
      decreased motility of tracts from 5-day old males, but did not alter motility of
      tracts from 8-day old males. Castration of larvae significantly suppressed
      reproductive tract motility in subsequent 8-day old adults compared with those of
      intact or sham-operated adults. Castration also suppressed seminal vesicle size.
      Lastly, we assessed the presence and distribution of proctolin-like and
      allatostatin-like immunoreactivity in tissues. Immunoreactivity to FGLa AST and
      proctolin was widespread, occurring in the brain and ventral ganglia.
      Surprisingly, we did not detect immunoreactivity to either FGLa AST or proctolin
      within the reproductive system; however, proctolin immunoreactivity was evident
      in nerves extending from the terminal ganglion of 8-day, but not 0-day, males.
      Collectively, these experiments demonstrate that the male earwig reproductive
      system is an appropriate model for use in addressing sexual maturation and
      activities in male insects.

PMID- 18824121
TI  - Phosphomannose isomerase and phosphomannomutase gene disruptions in Streptomyces
      nodosus: impact on amphotericin biosynthesis and implications for glycosylation
      engineering.
AB  - Streptomycetes synthesise several bioactive natural products that are modified
      with sugar residues derived from GDP-mannose. These include the antifungal
      polyenes, the antibacterial antibiotics hygromycin A and mannopeptimycins, and
      the anticancer agent bleomycin. Three enzymes function in biosynthesis of GDP
      mannose from the glycolytic intermediate fructose 6-phosphate: phosphomannose
      isomerase (PMI), phosphomannomutase (PMM) and GDP-mannose pyrophosphorylase
      (GMPP). Synthesis of GDP-mannose from exogenous mannose requires hexokinase or
      phosphotransferase enzymes together with PMM and GMPP. In this study, a region
      containing genes for PMI, PMM and GMPP was cloned from Streptomyces nodosus,
      producer of the polyenes amphotericins A and B. Inactivation of the manA gene for
      PMI resulted in production of amphotericins and their aglycones, 8
      deoxyamphoteronolides. A double mutant lacking the PMI and PMM genes produced 8
      deoxyamphoteronolides in good yields along with trace levels of glycosylated
      amphotericins. With further genetic engineering these mutants may activate
      alternative hexoses as GDP-sugars for transfer to aglycones in vivo.

PMID- 18824122
TI  - CB(1) receptor antagonism: biological basis for metabolic effects.
AB  - The endocannabinoid system (ECS) is a complex physiologic system that affects
      metabolic pathways. A dysregulated ECS has been demonstrated in animal models of
      obesity and the expression of the cannabinoid type 1 (CB(1)) receptor in both
      brain and peripheral tissues suggests that selective antagonism at this receptor
      could target multiple tissues involved in metabolic homeostasis. In clinical
      trials with obese patients, treatment with the CB(1) receptor antagonist
      rimonabant was associated with clinically meaningful weight loss, as well as
      improved serum lipids and glycemic control. The biological basis for the
      metabolic effects of rimonabant (SR141716) appears to involve the modulation of
      metabolism through antagonism at a single receptor with several target organs.

PMID- 18824123
TI  - Bacteriophage lysins as effective antibacterials.
AB  - Lysins are highly evolved enzymes produced by bacteriophage (phage for short) to
      digest the bacterial cell wall for phage progeny release. In Gram-positive
      bacteria, small quantities of purified recombinant lysin added externally results
      in immediate lysis causing log-fold death of the target bacterium. Lysins have
      been used successfully in a variety of animal models to control pathogenic
      antibiotic resistant bacteria found on mucosal surfaces and infected tissues. The
      advantages over antibiotics are their specificity for the pathogen without
      disturbing the normal flora, the low chance of bacterial resistance to lysins,
      and their ability to kill colonizing pathogens on mucosal surfaces, a capacity
      previously unavailable. Thus, lysins may be a much needed anti-infective in an
      age of mounting antibiotic resistance.

PMID- 18824124
TI  - Challenges facing drug development for malaria.
AB  - Malaria is a significant cause of morbidity and mortality in the developing
      world. Until recently malaria was winning but with increase in funding
      particularly from philanthropic groups the ability to control malaria is again
      possible. There are still many challenges to developing the next generations of
      anti-malarials. This article will briefly discuss the challenges and the advance
      that are being made.

PMID- 18824125
TI  - Bacteriophage genomics.
AB  - The past three years have seen an escalation in the number of sequenced
      bacteriophage genomes with more than 500 now in the NCBI phage database,
      representing a more than threefold increase since 2005. These span at least 70
      different bacterial hosts, with two-thirds of the sequenced genomes of phages
      representing only eight bacterial hosts. Three key features emerge from the
      comparative analysis of these genomes. First, they span a very high degree of
      genetic diversity, suggesting early evolutionary origins. Second, the genome
      architectures are mosaic, reflecting an unusually high degree of horizontal
      genetic exchange in their evolution. Third, phage genomes contain a very high
      proportion of novel genetic sequences of unknown function, and probably represent
      the largest reservoir of unexplored genes. With an estimated 10(31) bacterial and
      archael viruses in the biosphere, our view of the virosphere will draw into
      sharper focus as further bacteriophage genomes are characterized.

PMID- 18824126
TI  - Targeting virulence traits: potential strategies to combat extraintestinal
      pathogenic E. coli infections.
AB  - Extraintestinal pathogenic Escherichia coli (ExPEC) are able to colonize, invade
      and induce disease in body niches outside the gastrointestinal tract. The
      emergence of (multi)resistant ExPEC variants calls for alternative antimicrobial
      strategies with a reduced pressure on selection of antibiotic resistances. We
      report on recent research efforts to target such virulence traits or to interfere
      with ExPEC colonization of extraintestinal niches in order to prevent or treat
      ExPEC infections and reduce the risk of further emergence of antibiotic
      resistances.

PMID- 18824127
TI  - Small-molecule catalysts of oxidative protein folding.
AB  - Oxidative protein folding occurs both in vivo and in vitro and involves the
      formation and rearrangement of protein disulfide bonds (SS bonds). In vivo these
      reactions are catalyzed by enzymes, including the eukaryotic enzyme protein
      disulfide isomerase (PDI). Using the physical properties of PDI as a guide,
      several small-molecule catalysts of oxidative protein folding have been designed,
      synthesized, and tested. These small molecules can improve the folding rate of
      the model substrate ribonuclease A by a factor of over 10 and improve the yield
      by up to a factor of 3 over traditional conditions. The molecules have also been
      demonstrated to significantly improve the in vivo folding of proteins as well.

PMID- 18824128
TI  - Taking femtosecond snapshots of RNA conformational dynamics and complexity.
AB  - RNA conformational dynamics have been a subject of extensive biophysical studies
      by spectroscopic and computational techniques. Application of femtosecond time
      resolved spectroscopy is a new addition to this field, where the technique is
      specifically designed to probe the ruggedness of RNA conformational landscape and
      recognition modes. Such technique allows resolution of heterogeneous
      conformations within a complex ensemble. Recent applications on GNRA tetraloops,
      dangling ends, and RNA-peptide complexes produced more quantitative and dynamic
      pictures for these motifs and interactions, including detection of alternative
      structures that have been overlooked. Integration of the ultrafast dynamics
      approach with other biophysical techniques promises to be a more powerful
      approach for providing unique insights for addressing the challenging task of
      decoding RNA conformational dynamics and the understanding of the mechanisms of
      molecular recognition of RNA.

PMID- 18824129
TI  - Hepatic iron content corresponds with the susceptibility of lymphocytes to
      oxidative stress in neonatal pigs.
AB  - The pig is born with limited iron supplies. If not supplemented, piglets
      dramatically loose their body iron stores during the first few days of postnatal
      life. The aim of this study was to investigate the influence of hepatic iron
      content on susceptibility of blood cells to oxidative stress. Four 1-day-old and
      three 7-days-old animals were used in this study. The alkaline version of the
      comet assay was used to measure DNA damage. As expected, iron body stores of non
      supplemented animals decrease significantly during the first 4 days of life.
      However, no difference in background DNA damage was found between untreated
      lymphocytes from these two groups of animals, despite the difference in their
      hepatic iron content. Interestingly, DNA damage induced by H2O2 and X-radiation
      in lymphocytes taken from 1-day-old piglets was significantly higher than in
      those taken from 7-days-old animals. In contrast, NaOCl or tert-butyl-hydroxide
      also induced significant amounts of DNA damage, but no differences between the
      two groups of piglets were found. Our data show that decreased hepatic iron
      content corresponds with decreased susceptibility of blood lymphocytes to
      oxidative stressors.

PMID- 18824130
TI  - Population genomics: modeling the new and a renaissance of the old.

PMID- 18824131
TI  - Stress, anxiety, depression, and epilepsy: investigating the relationship between
      psychological factors and seizures.
AB  - OBJECTIVE: The goal of the study described here was to examine the
      interrelationship between psychological factors (anxiety, stress, and depression)
      and seizures. METHODS: In this longitudinal cohort study, data on anxiety,
      depression, perceived stress, and seizure recency (time since last seizure) and
      frequency were collected at two time points using standard validated
      questionnaire measures. Empirically based models with psychological factors
      explaining change in (1) seizure recency and (2) seizure frequency scores across
      time were specified. We then tested how these psychological factors acted
      together in predicting seizure recency and frequency. Our data were used to test
      whether these models were valid for the study population. Latent variable
      structural equation modeling was used for the analysis. RESULTS: Four hundred
      thirty-three of the 558 individuals who initially consented to participate
      provided two waves of data for this analysis. Stress (beta=0.25, P<0.01), anxiety
      (beta=0.30, P<0.01), and depression (beta=0.30, P<0.01) all predicted change in
      seizure recency. However, it was depression that mediated the relationship of
      both anxiety and stress with modeled change in seizure recency (beta=0.19,
      P<0.01) and seizure frequency (beta=0.30, P<0.01) over time. CONCLUSION:
      Depression mediates the relationship between stress and anxiety and change in
      seizure recency and seizure frequency. These findings highlight the importance of
      depression management in addition to seizure management in the assessment and
      treatment of epilepsy in an adult population.

PMID- 18824132
TI  - Sexual communication via peptide and protein pheromones.
AB  - Pheromones are specific substances utilized by various organisms for
      intraspecific communication about sex, strain, or species. Although pheromones in
      terrestrial animals tend to be volatile airborne chemicals, large non-volatile
      molecules such as peptides and proteins are also utilized for sociosexual
      communication. Peptide pheromones are recognized by specific receptors expressed
      in the vertebrate vomeronasal organ that comprises a unique chemosensory system.
      The information is sent to the hypothalamic area wherein the signal is further
      integrated, leading to various pheromonal outputs. In this review, current
      knowledge on the structure and function of peptide and protein pheromones in
      vertebrates as well as the mechanisms underlying receptor-mediated signal
      processing will be summarized. The present review will also discuss why, from
      chemical and ecological points of view, peptide pheromones evolved.

PMID- 18824133
TI  - Countering imbalanced datasets to improve adverse drug event predictive models in
      labor and delivery.
AB  - BACKGROUND: The IOM report, Preventing Medication Errors, emphasizes the overall
      lack of knowledge of the incidence of adverse drug events (ADE). Operating rooms,
      emergency departments and intensive care units are known to have a higher
      incidence of ADE. Labor and delivery (L&D) is an emergency care unit that could
      have an increased risk of ADE, where reported rates remain low and under
      reporting is suspected. Risk factor identification with electronic pattern
      recognition techniques could improve ADE detection rates. OBJECTIVE: The
      objective of the present study is to apply Synthetic Minority Over Sampling
      Technique (SMOTE) as an enhanced sampling method in a sparse dataset to generate
      prediction models to identify ADE in women admitted for labor and delivery based
      on patient risk factors and comorbidities. RESULTS: By creating synthetic cases
      with the SMOTE algorithm and using a 10-fold cross-validation technique, we
      demonstrated improved performance of the Naive Bayes and the decision tree
      algorithms. The true positive rate (TPR) of 0.32 in the raw dataset increased to
      0.67 in the 800% over-sampled dataset. CONCLUSION: Enhanced performance from
      classification algorithms can be attained with the use of synthetic minority
      class oversampling techniques in sparse clinical datasets. Predictive models
      created in this manner can be used to develop evidence based ADE monitoring
      systems.

PMID- 18824134
TI  - Long-term effects of candesartan and amlodipine on cardiovascular mortality and
      morbidity in Japanese high-risk hypertensive patients: rationale, design, and
      characteristics of candesartan antihypertensive survival evaluation in Japan
      extension (CASE-J Ex).
AB  - Candesartan Antihypertensive Survival Evaluation in Japan (CASE-J) trial was
      conducted to compare the effects of the angiotensin II receptor blocker (ARB)
      candesartan and the calcium channel blocker (CCB) amlodipine on the incidence of
      cardiovascular (CV) events in Japanese high-risk hypertensive patients. After
      3.2years follow-up, CV events rate was 17.6-17.7 per 1000 person-years in each
      group, which was much lower than we expected. Since it has not been known whether
      the same efficacy of two drugs is sustained beyond the current trial, a longer
      follow-up period will be needed. The Steering Committee of CASE-J trial decided
      to extend the trial for 3years as an observational study (CASE-J Ex). In CASE-J
      Ex, the primary end point is a composite of CV events and the secondary endpoints
      are all-cause death and new-onset diabetes. After Committee's decision, 245
      doctors agreed to participate in CASE-J Ex and 2236 patients (1141 with
      candesartan-based regimens and 1095 with amlodipine-based regimens) were re
      enrolled. The baseline characteristics of CASE-J Ex participants were similar to
      CASE-J participants and still balanced well between candesartan and amlodipine.
      Recently, the interest of antihypertensive treatment has focused to
      differentiation of the effects of antihypertensive agents on the incidence of CV
      events as well as blood pressure lowering effect. CASE-J Ex will clarify the long
      term effects of ARB and CCB on CV mortality and morbidity. Additionally, because
      the number of diabetic patients is increased, the evidences from CASE-J Ex will
      be valuable.

PMID- 18824135
TI  - A collaborative approach to the recruitment and retention of minority patients
      with diabetes in rural community health centers.
AB  - CONTEXT: Recruiting and retaining minorities from rural, community health centers
      is a challenge. Collaboration between the researchers and health center personnel
      and activities to enhance trust may improve results. PURPOSE: To describe
      recruitment and retention strategies and report results of a 12-month clinical
      trial of a telemedicine-based diabetes self-management intervention, conducted
      within a rural community health center. METHODS: Multi-level, multi-staged
      recruitment process including collaborative planning, data extraction, medical
      record review, telephone screen, 2 in-person enrollment visits and randomization.
      Target sample was adults >or=35 years of age with type 2 diabetes, glycated
      hemoglobin (GHb)>7% with no significant comorbidities to prevent safe
      participation. Follow-up visits occurred at 6 and 12 months post-randomization.
      FINDINGS: Of those eligible from medical record review, 65% were African
      American(AA)/other and female. Approximately 33% of those successfully contacted
      by telephone were randomized (n=165), yielding a predominately AA/other (73.9%)
      and female (74.5%) sample. Among those eligible at the Telephone Screen, a
      greater percentage of Non-Hispanic Whites (NHW) refused participation than
      AA/other (54.2% vs 45.8%), while a greater percentage of women refused compared
      to men (64.4% vs 35.6%). Significant baseline differences were found by ethnicity
      for education, insurance, transportation and diastolic blood pressure; by gender
      for income, transportation, weight, and home monitoring of blood glucose. Overall
      6 and 12 month retention rates were 90.9% and 82.4%, respectively, with a greater
      percentage of AA/Other and female participants retained. CONCLUSIONS: Our
      collaborative approach was successful in recruiting and retaining ethnically
      diverse study participants who reside in a rural underserved area of South
      Carolina. Differences in baseline characteristics and retention by ethnicity and
      gender were found. Successful translational research must allow for a
      collaborative approach addressing factors at the level of the community health
      center, key personnel, and patients in an effort to build trust for the purpose
      of advancing the science of translating research to practice.

PMID- 18824136
TI  - TLR-4 agonistic lipopolysaccharide upregulates interleukin-8 at the
      transcriptional and post-translational level in vascular smooth muscle cells.
AB  - Despite extensive studies on cellular responses to activation of Toll-like
      receptor-4 (TLR-4), it is not evident weather its activation affects gene
      expression of interleukin-8 (IL-8) in vascular smooth muscle cells (VSMCs).
      Therefore, this study has investigated whether and how TLR-4 influences IL-8
      expression in VSMCs. Exposure of aortic smooth muscle cells to TLR-4 agonistic
      lipopolysaccharide (LPS) not only enhanced release of IL-8 protein but also
      induced IL-8 gene transcript via promoter activation. The LPS-induced activation
      of IL-8 promoter was attenuated by dominant-negative MKK1, but not by dominant
      negative MKK3. The promoter activation was also impaired by dominant negative
      CCAAT/enhancer binding protein (C/EBP), IkappaB, and dominant negative c-Jun. In
      comparison with the mutation of the AP-1 binding site, the mutation of NF-kappaB
      site and C/EBP binding site in the IL-8 promoter region more significantly
      impaired the promoter activation. Moreover, both promoter activity and release of
      IL-8 were inhibited by U0126 and curcumin, but not by SB202190, epigallocatechin
      3-gallate and resveratrol. The present study reports that TLR-4-agonistic LPS
      upregulates IL-8 at the transcriptional and post-translational level in VSMCs,
      and that ERK1/2, NF-kappaB, and C/EBP play major roles in the upregulation of IL
      8.

PMID- 18824137
TI  - Clinical correlations of human cytomegalovirus strains and viral load in kidney
      transplant recipients.
AB  - Little is known about clinical differences associated with cytomegalovirus (CMV)
      infection by distinct strains in renal transplant patients. Different clinical
      pictures may be associated with specific viral genotypes, viral load, as well as
      host factors. The objective of this study was to identify CMV strains to
      determine viral load (antigenemia), and their correlation with clinical data in
      renal transplant recipients. Seventy-one patients were enrolled, comprising 91
      samples. After selection, polymorphonuclear cells were used to amplify and
      sequence the gB region of CMV DNA. The sequences were analyzed to ascertain the
      frequency of different genotypes. Additionally, the results of this study showed
      that the gB coding gene presents a great variability, revealing a variety of
      patterns: classical gB1 (1.4%), gB1V (46.4%), classical gB2 (35.2%), gB2V (2.8%),
      gB3 (1.4%), classical gB4 (4.9%) and gB4V (4.9%). The mean viral load in kidney
      transplant patient was 75.1 positive cells (1-1000). A higher viral load was
      observed in patients with genotype 4 infection. Statistically significant
      differences were detected between gB1 and gB4 (p=0.010), and between gB2 and gB4
      (p=0.021). The average numbers of positive cells in relation to clinical
      presentation were: 34.5 in asymptomatic, 49.5 in CMV associated syndrome and
      120.7 in patients with invasive disease (p=0.048). As a group, gB1 was the most
      frequent strain and revealed a potential risk for developing invasive disease.
      Viral load also seemed to be important as a marker associated with clinical
      presentation of the disease.

PMID- 18824138
TI  - Role of budding yeast Rad18 in repair of HO-induced double-strand breaks.
AB  - The Rad6-Rad18 complex mono-ubiquitinates proliferating cell nuclear antigen
      (PCNA) at the lysine 164 residue after DNA damage and promotes DNA polymerase eta
      (Poleta)- and Polzeta/Rev1-dependent DNA synthesis. Double-strand breaks (DSBs)
      of DNA can be repaired by homologous recombination (HR) or non-homologous end
      joining (NHEJ), both of which require new DNA synthesis. HO endonuclease
      introduces DSBs into specific DNA sequences. We have shown that Polzeta and Rev1
      localize to HO-induced DSBs in a Mec1-dependent manner and promote Ku-dependent
      DSB repair. However, Polzeta and Rev1 localize to DSBs independently of PCNA
      ubiquitination. Here we provide evidence indicating that Rad18-mediated PCNA
      ubiquitination stimulates DNA synthesis by Polzeta and Rev1 in repair of HO
      induced DSBs. Ubiquitination defective PCNA mutation or rad18Delta mutation
      confers the same DSB repair defect as rev1Delta mutation. Consistent with a role
      in DSB repair, Rad18 localizes to HO-induced DSBs in a Rad6-dependent manner.
      Unlike Polzeta or Rev1, Poleta is dispensable for repair of HO-induced DSBs. Ku
      and DNA ligase IV constitute a central NHEJ pathway. We also show that Polzeta
      and Rev1 act in the same pathway as DNA ligase IV, suggesting that Polzeta and
      Rev1 are involved in DNA synthesis during NHEJ. Our results suggest that Polzeta
      Rev1 accumulates at regions near DSBs independently of PCNA ubiquitination and
      then interacts with ubiquitinated PCNA to facilitate DNA synthesis.

PMID- 18824139
TI  - Gene cloning and enzymatic characteristics of a novel gamma-cyclodextrin-specific
      cyclodextrinase from alkalophilic Bacillus clarkii 7364.
AB  - A new gene, cda, was found in the downstream region of the cgt gene encoding
      cyclodextrin (CD) glucanotransferase from Bacillus clarkii 7364. Cda encoded by
      the cda was a cyclodextrinase that has extremely high specificity for gamma-CD.
      The rates of hydrolysis toward alpha- and beta-CD, maltooctaose and
      polysaccharides were less than 4% of that toward gamma-CD. Cda also has a
      transglycosylation activity, by which the maltotriose moiety was transferred from
      maltohexaose and maltopentaose. The comparison of the amino acid sequences
      between Cda and CD-degrading enzymes revealed the sequence of Cda has unique
      features. One of them is Gly247 next to the catalytic nucleophile Asp246. Most
      enzymes in GH family 13 have more bulky amino acids at this position. Other
      features in Cda are the lack of the N-domain in CD-degrading enzymes involving in
      the dimerization contributing to the preference of CDs and the existence of a
      long extra sequence in the C-terminus. Despite the lack of N-domain, Cda showed a
      dodecameric structure. The long extra sequence in the C-terminus might contribute
      to the oligomerization of Cda through a new mechanism. These unique features
      indicate that Cda is a novel type of CD-degrading enzyme.

PMID- 18824140
TI  - Effect of short-term exposure to zidovudine (AZT) on the expression of
      mitochondria-related genes in skeletal muscle of neonatal mice.
AB  - Zidovudine (3'-azido-3'-deoxythymidine; AZT) is the main anti-retroviral drug
      given to HIV-1-infected pregnant women during pregnancy and to their infants
      after birth to reduce mother-to-child transmission of the virus. In animal
      studies, however, a significant mitochondrial morphological damage has been
      reported in skeletal muscle as a consequence of transplacental or perinatal
      exposure to AZT. Because proper muscle function is highly dependent on efficient
      mitochondrial function and information on AZT-induced mitochondrial toxicity
      during neonatal exposure is limited, we investigated the effect of AZT on the
      expression of 542 mitochondria-related genes encoded by both nuclear and
      mitochondrial DNA in the skeletal muscle of infant male and female mice using
      microarray technology. Animals were treated orally by gavage with AZT at 0, 10,
      50, 100, and 200mg/kg body weight/day from postnatal day (PND) 1 through 8 and
      were sacrificed at 1- and 2-h following the last dose on PND 8. These doses in
      mice correspond to 0, 1.1, 5.5, 11.0, and 22.0mg/kg AZT in human infants [Center
      for Drug Evaluation and Research (CDER) 2005. Pharmacology and Toxicology,
      Guidance for industry. Estimating the maximum safe dose in initial clinical
      trials for therapeutics in adult healthy volunteers, p. 7.
      http://www.fda.gov/cder/guidance/index.htm.]. Microarray data were analyzed for
      effects of time, sex, treatment, and their interactions using a fixed effect
      linear model. The results showed modest, but significant, dose-related responses
      in the expression level of genes associated with apoptosis, fatty acid
      metabolism, mitochondrial DNA maintenance, and various mitochondrial membrane
      transporters. The transcription levels were not significantly different at both
      time points and were not sex dependent. The results suggest that changes in
      expression of mitochondria-related genes in skeletal muscle may be an initial
      response to short-term AZT exposure in infant mice.

PMID- 18824141
TI  - Rat visceral yolk sac (VYS) and placenta mitochondrial features during the
      placentation period.
AB  - The transference of the nutritional function from the VYS to the chorioallantoic
      placenta during middle pregnancy is a key event for the activation of embryo
      oxidative metabolism. However, the metabolic adaptations occurring in these
      tissues during this critical period have not been studied to date. Herein, we
      investigate the VYS and placenta mitochondrial adaptations throughout gestational
      days 11, 12 and 13. The results reflect that, during the placentation period,
      mitochondrial proliferation predominates over differentiation in placenta.
      Besides, VYS development and mitochondriogenesis show a slowdown despite
      maintaining the mitochondrial OXPHOS capacities, hence becoming a supporting
      tissue until the placenta functions are completely available.

PMID- 18824142
TI  - Modulatory effects of histamine on cat carotid body chemoreception.
AB  - Histamine has been proposed to be an excitatory transmitter between the carotid
      body (CB) chemoreceptor (glomus) cells and petrosal ganglion (PG) neurons. The
      histamine biosynthetic pathway, its storage and release, as well as the presence
      of histamine H1, H2 and H3 receptors have been found in the CB. However, there is
      only indirect evidence showing the presence of histamine in glomus cells, or
      weather its application produces chemosensory excitation. Thus, we studied the
      histamine immunocytochemical localization in the cat CB, and the effects of
      histamine, and H1, H2 and H3 receptor blockers on carotid sinus nerve (CSN)
      discharge, using CB and PG preparations in vitro. We found histamine
      immunoreactivity in dense-cored vesicles of glomus cells. Histamine induced dose
      dependent increases in CSN discharge in the CB, but not in the PG. The H1
      antagonist pyrilamine reduced the CB responses induced by histamine, the H2
      antagonists cimetidine and ranitidine had no effect, while the H3-antagonist
      thioperamide enhanced histamine-induced responses. Present data suggests that
      histamine plays an excitatory modulatory role in the generation of cat CB
      chemosensory activity.

PMID- 18824143
TI  - Developmental hyperoxia attenuates the hypoxic ventilatory response in Japanese
      quail (Coturnix japonica).
AB  - Early life experiences can influence development of the respiratory control
      system. We hypothesized that chronic hyperoxia (60% O(2)) during development
      would attenuate the hypoxic ventilatory response (HVR) of Japanese quail
      (Coturnix japonica), similar to the effects of developmental hyperoxia in
      mammals. Quail were exposed to hyperoxia during prenatal development, during
      postnatal development, or during both prenatal and postnatal development (for
      approximately 2 or 4 weeks). HVR (11% O(2)) was subsequently assessed in adults
      (>6 weeks old) via barometric plethysmography and compared to quail raised in
      normoxia (i.e., control). The HVR of quail exposed to hyperoxia both prenatally
      and postnatally was reduced 50-60% compared to control quail whereas postnatally
      exposed quail exhibited normal HVR. The effects of prenatal hyperoxia on HVR were
      equivocal and depended on how HVR was expressed. We conclude that developmental
      exposure to 60% O(2) attenuates the HVR in quail and that the critical period for
      this plasticity encompasses the late prenatal and early postnatal periods.

PMID- 18824144
TI  - Increased peripheral chemosensitivity via dopaminergic manipulation promotes
      respiratory instability in lambs.
AB  - Periodic breathing (PB) is an instability of the respiratory control system
      believed to be mediated principally by the peripheral chemoreceptors. We
      hypothesised that domperidone, a dopamine D(2)-receptor antagonist that increases
      carotid body sensitivity to O(2) and CO(2), would promote PB through an increase
      in the loop gain (LG) of the respiratory control system. Domperidone
      significantly increased controller gain for oxygen (p<0.05) and gave rise,
      following post-hyperventilation apnea, to an increased incidence of PB (14% vs.
      86%), an increased PB epoch duration, and a decrease in duty ratio of PB
      (p<0.001); these changes are consistent with domperidone increasing LG. Although
      domperidone increased controller gain for CO(2) (p<0.05), the contribution of
      Pa(CO)(2) oscillations to the genesis of PB in the lamb remained small. We
      conclude that domperidone increases LG in the lamb via an increase in controller
      gain for oxygen. Our study demonstrates that a quantitative understanding of the
      factors that determine LG provides insight into the cause of PB.

PMID- 18824145
TI  - Venous pressure and dyspnea on exertion in cardiac failure: was Tinsley Randolph
      Harrison right?
AB  - More than 70 years ago, Harrison and his group proposed that in the absence of
      pulmonary edema, an increased systemic venous pressure could be a major source of
      dyspnea upon exertion in cardiac patients. Harrison provided evidence that in
      resting animals systemic venous pressure can affect ventilatory control through
      afferent information originating from the right side of the central circulation
      (i.e. right ventricle and large veins) via the vagus nerves. This review explores
      the concept that "increased venous pressure acts as a cause of dyspnea", which
      emerged from the remarkable work performed by Harrison and co-workers. Their
      conclusion will be however extended by developing the hypothesis that the load
      imposed on the venous blood returning from the skeletal muscles during any
      muscular activity is sensed by slow conducting muscle afferent fibers and
      provides a source of dyspnea in heart failure patients.

PMID- 18824146
TI  - Muscimol dialysis into the caudal aspect of the Nucleus tractus solitarii of
      conscious rats inhibits chemoreception.
AB  - We studied the effects on chemoreception of bilateral focal inhibition of the
      caudal Nucleus tractus solitarii (cNTS) by microdialysis of muscimol (0.5 mM) in
      rats during wakefulness and NREM sleep at two temperatures, 24 degrees C and 30
      degrees C, just below and within the thermoneutral zone, respectively. Body
      temperature and VO2 did not differ at these two temperatures. The CO2 response (%
      increase in V(E)/VO2) did not differ at 24 degrees C vs. 30 degrees C and
      muscimol inhibited the CO2 response equally at both temperatures. In contrast,
      the hypoxic response (% increase in V(E)/VO2) was greater at 30 degrees C than at
      24 degrees C and muscimol inhibited it only at 30 degrees C. These effects were
      similar in wakefulness and NREM sleep. We conclude that: (1) ambient temperature
      can affect the V(E)/VO2 response to hypoxia but not hypercapnia and (2) at 24
      degrees C muscimol in the cNTS affects the CO2 response but not the hypoxic
      response providing indirect support for the presence of chemoreception within the
      NTS.

PMID- 18824148
TI  - Proteomic analysis of the porcine platelet proteome and alterations induced by
      thrombin activation.
AB  - Platelets are enucleated cells derived from bone marrow megakaryocytes and
      defects in platelet functions could be involved in many cardiovascular diseases.
      Proteomics can be used to provide a new insight in the study of these platelet
      functions and can help to identify the biochemical events underlying platelet
      activation. In this study, we have obtained a reference 2-DE map of porcine
      platelet proteins. A large number of cytoskeletal and metabolic proteins were
      found as well as some proteins related to cell mobility and immunological
      functions. Other proteins implicated in the cell signalling process, transport or
      apoptosis were also identified. Moreover, we have analysed, by 2D-DIGE
      methodology, quantitative modifications of platelet proteins following their
      activation by thrombin. 26 spots exhibited statistically significant differences,
      and a total of 16 spots corresponding to 13 different proteins were successfully
      identified. Using Ingenuity Pathway Analysis, the association of the deregulated
      proteins with canonical pathways highlighted two major pathways; coagulation
      system and integrin signalling. These results confirm that this proteomic
      approach (based on 2D-DIGE, mass spectrometry and bioinformatic and pathway
      databases) has proved to be a powerful tool when applied to studying signalling
      pathways that could play a relevant role in the activation of platelets.

PMID- 18824149
TI  - Recent highlights of EU-funded medical research projects. Provided by CORDIS, the
      official information service for participation in the EU research programmes.

PMID- 18824147
TI  - Proteomic changes during intestinal cell maturation in vivo.
AB  - Intestinal epithelial cells undergo progressive cell maturation as they migrate
      along the crypt-villus axis. To determine molecular signatures that define this
      process, proteins differentially expressed between the crypt and villus were
      identified by 2D-DIGE and MALDI-MS. Forty-six differentially expressed proteins
      were identified, several of which were validated by immunohistochemistry.
      Proteins upregulated in the villus were enriched for those involved in brush
      border assembly and lipid uptake, established features of differentiated
      intestinal epithelial cells. Multiple proteins involved in glycolysis were also
      upregulated in the villus, suggesting increased glycolysis is a feature of
      intestinal cell differentiation. Conversely, proteins involved in nucleotide
      metabolism, and protein processing and folding were increased in the crypt,
      consistent with functions associated with cell proliferation. Three novel paneth
      cell markers, AGR2, HSPA5 and RRBP1 were also identified. Notably, significant
      correlation was observed between overall proteomic changes and corresponding gene
      expression changes along the crypt-villus axis, indicating intestinal cell
      maturation is primarily regulated at the transcriptional level. This proteomic
      profiling analysis identified several novel proteins and functional processes
      differentially induced during intestinal cell maturation in vivo. Integration of
      proteomic, immunohistochemical, and parallel gene expression datasets demonstrate
      the coordinated manner in which intestinal cell maturation is regulated.

PMID- 18824150
TI  - Integrated farming: why organic farmers should use transgenic crops.
AB  - The concept of organic farming is summarised and compared as an example to
      farming with biotechnology-derived crops. If done within an ecological concept,
      both methods can be seen as environmentally acceptable. Organic farming does not
      offer consistent arguments for the rejection of transgenic crops. Some arguments
      (from genomics to biodiversity) are discussed in order to demonstrate that the
      contrast between both farming systems is rated too high and that it is possible
      to overcome the divide. In this way the ground is prepared for a proposal on how
      to merge those otherwise incompatible agricultural management systems, a proposal
      that also will have to build on a new concept of sustainability. It will be dealt
      with in the second part of the article in the next issue of New Biotechnology.

PMID- 18824151
TI  - CEN Workshop establishes an international Laboratory Biorisk Management Standard.

PMID- 18824152
TI  - Diabetes research for developing countries.
AB  - EAGLES investigations into the specific needs for diabetes research in developing
      countries, and Europe's potential to support that research [European Union and
      Diabetes
      http://ec.europa.eu/health/ph_information/dissemination/diseases/diabetes_en.htm,
      EU Research on Diabetes
      http://ec.europa.eu/research/leaflets/diabetes/index_en.html] reach nine major
      conclusions. In each case, they involve tuning European research to have the
      greatest impact in the shortest possible time, by understanding and respecting
      developing countries' conditions of health, politics and economics. Major
      recommendations arise from the lack of national population-based epidemiology to
      enable planning and convince political powers of the need for action; from
      countries' low healthcare budgets, entailing needs for the cheapest possible
      interventions; from the need to investigate interventions specifically tuned to
      national circumstances; and finally from the needs for specific local biomedical
      research, such as studies into the several unique African phenotypes of the
      disease. The details of our nine recommendations can be seen at the end of the
      report.

PMID- 18824153
TI  - A homogeneous resonance energy transfer-based assay to monitor MutS/DNA
      interactions.
AB  - Probing the interactions of the DNA mismatch repair protein MutS with altered and
      damaged DNA is of great interest both for the understanding of the mismatch
      repair system function and for the development of tools to detect mutations. Here
      we describe a homogeneous time-resolved fluorescence (HTRF) assay to study the
      interactions of Escherichia coli MutS protein with various DNA substrates. First,
      we designed an indirect HTRF assay on a microtiter plate format and demonstrated
      its general applicability through the analysis of the interactions between MutS
      and mismatched DNA or DNA containing the most common lesion of the anticancer
      drug cisplatin. Then we directly labeled MutS with the long-lived fluorescent
      donor molecule europium tris-bipyridine cryptate ([TBP(Eu(3+))]) and demonstrated
      by electrophoretic mobility shift assay that this chemically labeled protein
      retained DNA mismatch binding property. Consequently, we used [TBP(Eu(3+))]-MutS
      to develop a faster and simpler semidirect HTRF assay.

PMID- 18824154
TI  - Mapping the putative binding site for uPA protein in Esophageal Cancer-Related
      Gene 2 by heteronuclear NMR method.
AB  - Esophageal Cancer-Related Gene 2 (ECRG2) is a novel member of the KAZAL-type
      serine proteinase inhibitor family and plays an important role in the inhibition
      of human esophageal cancer cell proliferation. The previous studies have shown
      that ECRG2 can bind the urokinase-type plasminogen activator (uPA)/plasmin system
      and inhibit its activity. In this study, the strategy of cloning, overexpression,
      and purification of ECRG2 for obtaining a properly folded ECRG2 with accurately
      formed disulfide bonds was established. The heteronuclear NMR experiments were
      performed with isotope labeled ECRG2 to investigate the binding interface of the
      protein with uPA. The sequence regions of ECRG2 for uPA binding were determined.
      Analysis indicates that the uPA-binding loops of ECRG2 are in correspondence with
      the reactive site loops for binding of serine proteinase in turkey ovomucoid
      third domain (OMTKY3). The structural similarity of ECRG2 to OMTKY3 was
      identified and a model for ECRG2 was proposed.

PMID- 18824155
TI  - Differential distribution of synGAP alpha1 and synGAP beta isoforms in rat
      neurons.
AB  - The synaptic Ras-GTPase activating protein synGAP is a brain-specific protein of
      approximately 130 kDa and is a negative regulator of Ras. We previously reported
      5 C-terminal isoforms of synGAP (alpha1, alpha2, beta1/2, beta 3/4 and gamma) [Li
      et al., 2001, J. Biol. Chem. 276: 21417-21424]. In this study, we investigated
      the expression profiles of the two major isoforms, synGAP alpha1 and synGAP beta,
      in the adult rat brain and cultured neurons of the rat hippocampus. Examination
      of pepsin-pretreated brain sections demonstrated that both isoforms were
      expressed mainly in the forebrain structures, which suggests their association
      with postsynaptic density. The distribution of the synGAP alpha1 and beta (beta1
      4) isoforms in the adult rat brain was clearly different in cerebellum,
      hippocampus, cerebral cortex, septum and olfactory bulb. In particular, synGAP
      alpha1 was specifically localized to the cerebellar glomeruli, dense synaptic
      sites. From the analysis using cultured neurons, unique expression of synGAP beta
      was found in a neuron with a sea urchin-like morphology, possibly a star
      pyramidal neuron, in which the synGAP beta expression was relatively high, in
      particular, at the distal part of its processes. SynGAP alpha1 was mostly or
      specifically localized to excitatory postsynaptic sites, whereas synGAP beta was
      present at both excitatory and inhibitory postsynaptic sites. Finally, there are
      more non-synaptic clusters in dendrites in the case of synGAP beta than synGAP
      alpha1. Thus, the two synGAP isoforms, alpha1 and beta, distribute differently in
      neuronal cells and the brain.

PMID- 18824156
TI  - Stereo-selective neuroprotection against stroke with vitamin A derivatives.
AB  - In this study we evaluated the neuroprotective potential of vitamin A (all-trans
      retinol), and its geometric isomers, all-trans retinoic acid and 9-cis retinoic
      acid, in a focal model of ischemia. A 60 minute middle cerebral artery occlusion
      in C57 mice resulted in over 50% hemispheric infarction. Vitamin A (retinol) and
      its derivatives were administered as two i.p. injections immediately prior to and
      following ischemia. A reduction in infarct volume was observed with all-trans
      retinol, in a dose-dependent manner: maximum protection was observed with a 10
      mg/kg dose. A similar protective profile was observed with all-trans retinol, but
      not the stereo-isomer 9-cis retinoic acid. Administration of the derivatives 1 h
      following ischemia did not produce significant protection. Taken together these
      data suggest a possible use of vitamin A derivatives as an acute neuroprotective
      strategy for stroke.

PMID- 18824157
TI  - A morphological and electrophysiological study on the postnatal development of
      oligodendrocyte precursor cells in the rat brain.
AB  - A widespread population of cells in CNS is identified by specific expression of
      the NG2 chondroitin sulphate proteoglycan and named as oligodendrocyte precursor
      cell (OPC). OPCs may possess stem cell-like characteristics, including
      multipotentiality in vitro and in vivo. It was proposed that OPCs in the CNS
      parenchyma comprise a unique population of glia, distinct from oligodendrocytes
      and astrocytes. This study confirmed that NG2 immunoreactive OPCs were
      continuously distributed in cerebral cortex and hippocampus during different
      postnatal developmental stages. These cells rapidly increased in number over the
      postnatal 7 days and migrate extensively to populate with abundant processes both
      in developing cortex and hippocampus. The morphology of OPCs exhibited extremely
      complex changes with the distribution of long distance primary process gradually
      increased from neonatal to adult CNS. Immunohistochemical studies showed that
      OPCs exhibited the morphological properties that can be distinguished from
      astrocytes. The electrophysiological properties showed that OPCs expressed a
      small amount of inward Na(+) currents which was distinguished from Na(+) currents
      in neurons owing to their lower Na-to-K conductance ratio and higher command
      voltage step depolarized maximum Na(+) current amplitude. These observations
      suggest that OPCs can be identified as the third type of macroglia because of
      their distribution in the CNS, the morphological development in process diversity
      and the electrophysiological difference from astrocyte.

PMID- 18824158
TI  - The firing activity of presumed cholinergic and non-cholinergic neurons of the
      pedunculopontine nucleus in 6-hydroxydopamine-lesioned rats: an in vivo
      electrophysiological study.
AB  - Several studies have shown that the neuronal activity of the pedunculopontine
      nucleus is increased in Parkinson's disease. In the present study, the changes
      were examined in the firing rate and firing pattern of presumed cholinergic and
      non-cholinergic neurons in the pedunculopontine nucleus of 6-hydroxydopamine
      lesioned rats by using extracellular recording. In the lesioned rats, the mean
      firing rate of both presumed cholinergic and non-cholinergic neurons in the
      pedunculopontine nucleus increased significantly compared to normal rats. With
      regard to firing pattern, the majority of presumed cholinergic and non
      cholinergic neurons fired regularly in normal rats. After substantia nigra pars
      compacta-lesion, the percentage of presumed non-cholinergic neurons exhibiting
      irregular pattern increased significantly compared to normal rats, while having
      no significant change in the firing pattern of presumed cholinergic neurons.
      Collectively, these results indicate that the presumed cholinergic and non
      cholinergic neurons in the pedunculopontine nucleus are overactive in 6
      hydroxydopamine-lesioned rats, particularly, presumed non-cholinergic neuron
      firing is more irregular, which suggests that the firing activity of presumed
      cholinergic and non-cholinergic neurons is affected by the different afferents
      from the basal ganglia and related structures.

PMID- 18824159
TI  - Effects of eugenol on Na+ currents in rat dorsal root ganglion neurons.
AB  - Eugenol is an aromatic molecule found in several plants and widely used in
      dentistry for analgesic and antiseptic purposes. It inhibits pro-inflammatory
      mediators including nitric oxide synthase, cyclooxygenase and lipoxygenase. It
      also regulates ion channels involved in pain signaling, such as TRPV1 receptor,
      high-voltage-activated Ca(2+) channels, NMDA receptor and GABA(A) receptor. The
      expression and functional properties of voltage-gated Na(+) channels in primary
      sensory neurons are altered following inflammation or nerve injury. To elucidate
      an involvement of Na(+) channels in the eugenol-induced analgesia we investigated
      the effects of eugenol on tetrodotoxin-sensitive (TTX-S) and tetrodotoxin
      resistant (TTX-R) Na(+) currents in acutely dissociated rat dorsal root ganglion
      neurons. Eugenol inhibited TTX-S and TTX-R Na(+) currents in a concentration
      dependent manner. The K(d) values were 308 muM and 543 muM, respectively. Eugenol
      did not influence the activation voltage of either type of Na(+) current.
      However, eugenol moved the steady-state inactivation curves of both Na(+)
      currents to a hyperpolarizing direction and reduced the maximal Na(+) current.
      Thus eugenol appears to inhibit Na(+) currents through its interaction with both
      resting and inactivated Na(+) channels. The recovery from inactivation of both
      Na(+) currents was slowed by eugenol. The eugenol inhibition of Na(+) currents
      was not dependent on the stimulus frequency. The inhibition of Na(+) currents is
      considered as one of the mechanisms by which eugenol exerts analgesia.

PMID- 18824160
TI  - T6092C polymorphism of SLC22A12 gene is associated with serum uric acid
      concentrations in Korean male subjects.
AB  - BACKGROUND AND OBJECT: It has been suggested that the SLC22A12 gene polymorphism
      may be involved in the mechanism of renal urate handling. The purpose of the
      current study was to identify the effect of the T6092C polymorphism of the
      SLC22A12 gene on serum uric acid concentrations in the Korean population.
      METHODS: We examined 196 healthy subjects (141 males and 55 females) in this
      study. Among the SLC22A12 gene polymorphism, the T6092C polymorphism in intron 4
      at rs1529909 of the SLC22A12 gene was evaluated using denaturing high performance
      liquid chromatography analysis. Diverse clinical parameters of renal urate
      handling derived from fasting blood and urine samples, such as the serum uric
      acid concentration and the fractional excretion of uric acid (FEUA), were also
      assessed for identification of the relationship between genotypic variations.
      Statistical analysis was performed using the chi-square test, ANOVA test, and the
      Pearson correlation coefficient analysis to determine which indicators involved
      serum uric acid. And the significance of these indicators was then confirmed by
      multivariate regression analysis. RESULTS: The prevalence of the T6092C
      polymorphism (TT, TC, and CC) was 58.2%, 37.2%, and 4.6%, respectively. Only the
      concentration of serum uric acid and the FEUA in male subjects differed
      significantly among each genotype (p=0.038 and p=0.013, respectively). Serum uric
      acid concentrations in male subjects with the TT genotype were increased compared
      with those with the TC as well as the TC or CC genotypes (6.2+/-1.2 vs. 5.7+/
      1.3, p=0.039 and 6.2+/-1.2 vs. 5.6+/-1.3, p=0.019, respectively), whereas there
      was no significant difference between CC genotype and TT genotype in serum uric
      acid (p=0.066). No significant difference between clinical indicators and
      genotypes existed in females. The T6092C polymorphism of the SLC22A12 gene, serum
      creatinine, and the FEUA were significantly associated with the concentration of
      serum uric acid. CONCLUSION: This study showed that the T6092C polymorphism of
      the SLC22A12 gene may be involved in renal urate handling and the concentration
      of serum uric acid, in male subjects.

PMID- 18824161
TI  - Bioavailable estradiol in man: relationship with age and testosterone.
AB  - Sex hormones undergo decreases in aging men. Several studies have shown the
      association of low levels of bioavailable estradiol with osteoporosis in man. To
      allow a better approach of sex hormones influences, we evaluated bioavailable
      estradiol concentrations in men and its correlation with age and testosterone. We
      show that bioavailable estradiol decreases significantly with age. We provide
      reference values in men with normal testosterone levels.

PMID- 18824162
TI  - High glucose increases RAW 264.7 macrophages activation by lipoteichoic acid from
      Staphylococcus aureus.
AB  - BACKGROUND: Type 2 diabetes mellitus is associated with an increased risk of
      cardiovascular diseases and accelerated atherosclerosis, which has been
      associated to hyperglycemia and chronic inflammation. Activated macrophages are
      described to participate in atherosclerosis due to foam cell formation and pro
      inflammatory mediators production. Bacterial infections are described to
      accelerate atherosclerosis, moreover, gram-positive and negative bacterial DNA
      was described in atherosclerotic plaques. METHODS: We studied the glucose
      modulation of RAW 264.7 macrophages activation by the gram-positive bacterial
      antigen lipoteichoic acid (LTA), evaluating nitrite production, tumor necrosis
      factor alpha secretion and matrix metalloproteinase 9 activity. RESULTS: High
      glucose increased macrophages activation by LTA, evidenced by exacerbated nitric
      oxide and tumor necrosis factor alpha production, as well matrix
      metalloproteinase 9 secretion. CONCLUSIONS: These effects could contribute to
      atherosclerotic risk parameters, like atherome plaque instability, and
      participate in chronic inflammation present in type 2 diabetes.

PMID- 18824163
TI  - Comparison and validation of point of care lactate meters as a replacement for
      fetal pH measurement.
AB  - OBJECTIVE: To validate a point of care lactate device to replace fetal pH
      measurement. STUDY DESIGN AND METHODS: Cord blood samples drawn immediately
      following delivery were tested on the Nova Lactate Plus and ARKRAY Lactate Pro,
      the Corometrics 220 pH System, and the Vitros chemistry analyzer (used as lactate
      reference). RESULTS: Nova demonstrated a constant positive bias relative to the
      lactate reference method; while the Lactate Pro correlated well with the
      reference method up to 6 mmol/L. Receiver operating characteristic (ROC) curve
      analysis showed optimal sensitivity and specificity for predicting pH<7.20 at
      lactate values of 6.8 mmol/L for the Nova and 4.8 mmol/L for the Lactate Pro.
      CONCLUSION: Using Lactate Pro the best cut-off for predicting pH< or =7.20 was
      4.8 mM; which coincides with current clinical cut-offs. Thus any lactate device
      that correlates well with the laboratory reference method can be used with a
      clinical cut-off of 4.8 mmol/L.

PMID- 18824164
TI  - Improved cryopreservation by diluted vitrification solution with supercooling
      facilitating flavonol glycoside.
AB  - The effect of kaempferol-7-O-glucoside (KF7G), one of the supercooling
      facilitating flavonol glycosides which was originally found in deep supercooling
      xylem parenchyma cells of the katsura tree and was found to exhibit the highest
      level of supercooling-facilitating activity among reported substances, was
      examined for successful cryopreservation by vitrification procedures, with the
      aim of determining the possibility of using diluted vitrification solution (VS)
      to reduce cryoprotectant toxicity and also to inhibit nucleation at practical
      cooling and rewarming by the effect of supplemental KF7G. Examination was
      performed using shoot apices of cranberry and plant vitrification solution 2
      (PVS2) with dilution. Vitrification procedures using the original concentration
      (100%) of PVS2 caused serious injury during treatment with PVS2 and resulted in
      no regrowth after cooling and rewarming (cryopreservation). Dilution of the
      concentration of PVS2 to 75% or 50% (with the same proportions of constituents)
      significantly reduced injury by PVS2 treatment, but regrowth was poor after
      cryopreservation. It is thought that dilution of PVS2 reduced injury by
      cryoprotectant toxicity, but such dilution caused nucleation during cooling
      and/or rewarming, resulting in poor survival. On the other hand, addition of
      0.5mg/ml (0.05% w/v) KF7G to the diluted PVS2 resulted in significantly (p<0.05)
      higher regrowth rates after cryopreservation. It is thought that addition of
      supercooling-facilitating KF7G induced vitrification even in diluted PVS2
      probably due to inhibition of ice nucleation during cooling and rewarming and
      consequently resulted in higher regrowth. The results of the present study
      indicate the possibility that concentrations of routinely used VSs can be reduced
      by adding supercooling-facilitating KF7G, by which more successful
      cryopreservation might be achieved for a wide variety of biological materials.

PMID- 18824165
TI  - Wnt signaling is required for organization of the lens fiber cell cytoskeleton
      and development of lens three-dimensional architecture.
AB  - How an organ develops its characteristic shape is a major issue. This is
      particularly critical for the eye lens as its function depends on having
      appropriately ordered three-dimensional cellular architecture. Recent in vitro
      studies indicate that Wnt signaling plays key roles in regulating morphological
      events in FGF-induced fiber cell differentiation in the mammalian lens. To
      further investigate this the Wnt signaling antagonist, secreted frizzled-related
      protein 2 (Sfrp2), was overexpressed in lens fiber cells of transgenic mice. In
      these mice fiber cell elongation was attenuated and individual fibers exhibited
      irregular shapes and consequently did not align or pack regularly; microtubules,
      microfilaments and intermediate filaments were clearly disordered in these
      fibers. Furthermore, a striking feature of transgenic lenses was that fibers did
      not develop the convex curvature typically seen in normal lenses. This appears to
      be related to a lack of protrusive processes that are required for directed
      migratory activity at their apical and basal tips as well as for the formation of
      interlocking processes along their lateral margins. Components of the Wnt/Planar
      Cell Polarity (PCP) pathway were downregulated or inhibited. Taken together this
      supports a role for Wnt/PCP signaling in orchestrating the complex organization
      and dynamics of the fiber cell cytoskeleton.

PMID- 18824166
TI  - Formation and activation of fibroblast spheroids depend on fibronectin-integrin
      interaction.
AB  - Clustering of fibroblasts into spheroids induces a massive proinflammatory,
      proteolytic and growth-factor response, named nemosis, which promotes tumor cell
      invasiveness and differentiation of leukemia cells. We have now sought to
      investigate mechanisms leading to the formation of multicellular spheroids and
      subsequent activation of fibroblasts (nemosis). Cell lines either lacking
      fibronectin expression (FN-/-) or expressing FN with a mutated integrin-binding
      site (FNRGE/RGE) were unable to form compact spheroids. Furthermore, inhibition
      of FN synthesis by siRNA or functional inhibition of FN or its integrins impaired
      spheroid formation (alpha5, beta1) and quenched fibroblast activation (alphaV).
      The integrin ligand GRGDSP hexapeptide interfered with spheroid formation and
      induced activation of fibroblasts. Surprisingly, a 70 kDa FN fragment, which
      prevents deposition of FN matrix but does not interfere with FN-integrin
      interaction, prevented spheroid formation only marginally and did not block the
      activation. Our results present a new mechanism of fibroblast activation, which
      is initiated by interaction of FN with its integrin receptors.

PMID- 18824167
TI  - Long-term cyclic stretch controls pulmonary endothelial permeability at
      translational and post-translational levels.
AB  - We have previously described differential effects of physiologic (5%) and
      pathologic (18%) cyclic stretch (CS) on agonist-induced pulmonary endothelial
      permeability. This study examined acute and chronic effects of CS on agonist
      induced intracellular signaling and cell morphology in the human lung macro- and
      microvascular endothelial cell (EC) monolayers. Endothelial permeability was
      assessed by analysis of morphological changes, parameters of cell contraction and
      measurements of transendothelial electrical resistance. Exposure of both
      microvascular and macrovascular EC to 18% CS for 2-96 h increased thrombin
      induced permeability and monolayer disruption. Interestingly, the ability to
      promote thrombin responses was present in EC cultures exposed to 48-96 h of CS
      even after replating onto non-elastic substrates. In turn, physiologic CS
      preconditioning (72 h) attenuated thrombin-induced paracellular gap formation and
      MLC phosphorylation in replated EC cultures. Long-term preconditioning at 18% CS
      (72 h) increased the content of signaling and contractile proteins including Rho
      GTPase, MLC, MLC kinase, ZIP kinase, PAR1, caldesmon and HSP27 in the pulmonary
      microvascular and macrovascular cells. We conclude that short term CS regulates
      EC permeability via modulation of agonist-induced signaling, whereas long-term CS
      controls endothelial barrier at both post-translational level and via magnitude
      dependent regulation of pulmonary EC phenotype, signaling and contractile protein
      expression.

PMID- 18824168
TI  - Therapy with interferon-beta modulates endogenous catecholamines in lymphocytes
      of patients with multiple sclerosis.
AB  - OBJECTIVE: To investigate the endogenous dopaminergic/adrenergic system of
      lymphocytes in multiple sclerosis (MS) patients during treatment with interferon
      (IFN)-beta. METHODS: Patients with relapsing-remitting MS undergoing IFN-beta
      treatment were prospectively studied during the first year of treatment.
      Circulating lymphocytes were obtained at baseline and after 1, 3, 6 and 12 months
      of treatment and assayed for catecholamine (CA) production and mRNA expression of
      tyrosine hydroxylase (TH, the rate-limiting enzyme in the synthesis of CA),
      beta(2)-adrenoceptors (AR) and D2, D3 and D5 dopaminergic receptors (DR).
      RESULTS: In cells from patients treated with IFN-beta for 12 months the
      production of CA hugely increased and was less sensitive to IFN-gamma-induced
      inhibition. Expression of mRNA for TH, beta(2)-AR and DRD5 was already enhanced
      after 1 month and further increased up to 6-12 months of treatment. On the
      contrary, DRD2 mRNA progressively decreased and DRD3 mRNA did not significantly
      change over the whole study period. CONCLUSIONS: In MS patients IFN-beta
      treatment enhances the ability of lymphocytes to produce CA, and induces
      extensive modifications of both beta(2)-AR and DR-operated pathways. The clinical
      relevance of these effects deserves consideration.

PMID- 18824169
TI  - Intrathecal delivery of resiniferatoxin (RTX) reduces detrusor overactivity and
      spinal expression of TRPV1 in spinal cord injured animals.
AB  - Recently, it has been demonstrated that intrathecal delivery of resiniferatoxin
      (RTX) produces strong analgesia, even in models of bone cancer pain. RTX has been
      investigated to treat bladder dysfunction of spinal origin, applied by
      intravesical instillation. However, RTX delivered by this route was not
      completely satisfactory in controlling urinary incontinence and high intravesical
      pressure. Thus, the present study assessed the effects of intrathecal injections
      of RTX in bladder dysfunction in rats with spinal cord transection (SCT). Bladder
      function was evaluated in SCT rats 24 h following intrathecal administration of
      RTX. Detrusor overactivity and intravesical pressure were reduced in a dose
      dependent manner. This was accompanied by a decrease in spinal cord TRPV1 and
      CGRP, but not in IB4 binding sensory fibres. Also, intrathecal RTX induced a dose
      dependent reduction in spinal cord activation of the ERK pathway. Overall, our
      results show that intrathecal administration of RTX effectively reduces detrusor
      overactivity and reduces intravesical pressure in models of complete chronic
      spinal cord transection by suppressing the activity of TRPV1 expressing afferent
      fibres. Also, intrathecal RTX decreases sensory input, as shown by reduced spinal
      ERK activation. These findings might be relevant for the management of patients
      with spinal cord injuries.

PMID- 18824170
TI  - NF-kappaB activates transcription of the RNA-binding factor HuR, via PI3K-AKT
      signaling, to promote gastric tumorigenesis.
AB  - BACKGROUND & AIMS: HuR is a RNA-binding factor whose expression is commonly
      upregulated in some human tumor types. We explored the molecular mechanism
      underlying HuR elevation and its role in gastric cancer tumorigenesis. METHODS:
      HuR expression and subcellular localization were determined by polymerase chain
      reaction, immunoblot, and immunohistochemical analyses. Its effect on tumor
      growth was characterized using flow cytometry, terminal deoxynucleotidyl
      transferase-mediated deoxyuridine triphosphate nick-end labeling, and soft agar
      analyses. Luciferase reporter, chromatin immunoprecipitation, and electrophoretic
      mobility shift assays were used to measure transcriptional activation by nuclear
      factor kappaB (NF-kappaB) signaling. RESULTS: Compared with normal gastric
      tissues, HuR was expressed at higher levels in gastric tumors, particularly in
      advanced versus early tumors; this increase was associated with enhanced
      cytoplasmic translocation of HuR. HuR overexpression increased proliferation of
      tumor cells, activating the G(1) to S transition of the cell cycle, DNA
      synthesis, and anchorage-independent growth. Small interfering RNA-mediated
      knockdown of HuR expression reduced tumor cell proliferation and response to
      apoptotic stimuli. No genetic or epigenetic alterations of HuR were observed in
      gastric tumor cell lines or primary tumors; overexpression depended on
      phosphatidylinositol 3-kinase/AKT signaling and NF-kappaB activity. AKT
      activation increased p65/RelA binding to a putative NF-kappaB binding site in the
      HuR promoter, the stability of HuR target transcripts, and the cytoplasmic import
      of HuR. CONCLUSIONS: HuR is a direct transcription target of NF-kappaB; its
      activation in gastric cancer cell lines depends on phosphatidylinositol 3
      kinase/AKT signaling. HuR activation by this pathway has proliferative and
      antiapoptotic effects on gastric cancer cells.

PMID- 18824171
TI  - Serial culture of murine primary airway epithelial cells and ex vivo replication
      of human rhinoviruses.
AB  - Human rhinoviruses (HRV) are the primary etiological agents in cold infections,
      and represent a serious risk to individuals with chronic respiratory disease such
      as asthma. In order to develop treatment options for HRV infections, murine
      models are a crucial component in the study of infection mechanisms due to the
      wide array of reagents and techniques available to study murine immunology. We
      present here a cell culture system for studying isolated murine epithelial cell
      responses to HRV. Monolayers of primary mouse airway epithelial cells were
      maintained in a serial culture system, and the identity and purity of the cell
      population was confirmed via immunostaining (positive for cytokeratin, negative
      for vimentin). Infection of these cells with a minor group rhinovirus (HRV-1A)
      was evidenced by increases in viral RNA, de novo synthesis of viral proteins, and
      production of infectious virus. This model will be useful in experiments to
      define mechanisms of viral replication and host/virus interactions within airway
      epithelial cells.

PMID- 18824172
TI  - The role of TNF-alpha receptors p55 and p75 in acute myocardial
      ischemia/reperfusion injury and late preconditioning.
AB  - The specific role of TNF-alpha receptors I (TNFR-I, p55) and II (TNFR-II, p75) in
      myocardial ischemic injury remains unclear. Using genetically engineered mice, we
      examined the relative effects of TNF-alpha signaling via p55 and p75 in acute
      myocardial ischemia/reperfusion injury under basal conditions and in late
      preconditioning (PC). Wild-type (WT) (C57BL/6 and B6,129) mice and mice lacking
      TNF-alpha (TNF-alpha(-/-)), p55 (p55(-/-)), p75 (p75(-/-)), or both receptors
      (p55(-/-)/p75(-/-)) underwent 30 min of coronary occlusion and 24 h of
      reperfusion with or without six cycles of 4-min coronary occlusion/4-min
      reperfusion (O/R) 24 h earlier (ischemic PC). Six cycles of O/R reduced infarct
      size 24 h later in WT mice, indicating a late PC effect. This late PC-induced
      infarct-sparing effect was abolished not only in TNF-alpha(-/-) and p55(-/-)/p75(
      /-) mice, but also in p55(-/-) and p75(-/-) mice, indicating that TNF-alpha
      signaling via both p55 and p75 is necessary for the development of protection. In
      nonpreconditioned TNF-alpha(-/-), p55(-/-)/p75(-/-), and p75(-/-) mice, infarct
      size was similar to strain-matched WT mice. In contrast, infarct size in
      nonpreconditioned p55(-/-) mice was reduced compared with nonpreconditioned WT
      mice. We conclude that (i) unopposed p75 signaling (in the absence of p55)
      reduces infarct size following acute ischemia/reperfusion injury in naive
      myocardium, whereas unopposed p55 signaling (in the absence of p75) has no
      effect; and (ii) the development of the infarct-sparing effects of the late phase
      of PC requires nonredundant signaling via both p55 and p75 receptors. These
      findings reveal a fundamental, heretofore unrecognized, difference between the
      two TNF-alpha receptors in the setting of myocardial ischemia/reperfusion injury:
      that is, both p55 and p75 are necessary for the development of protection during
      late PC, but only signaling via p75 is protective in nonpreconditioned
      myocardium.

PMID- 18824173
TI  - Structural basis for the substrate specificity of bone morphogenetic protein
      1/tolloid-like metalloproteases.
AB  - Procollagen C-peptidase, also known as bone morphogenetic protein 1 (BMP-1), is a
      multidomain, zinc endopeptidase of the astacin M12A family. BMP-1 is the
      prototype of a small group of proteases that have key roles in extracellular
      matrix formation and morphogenesis. BMP-1, its splice form mTLD, and the related
      proteases TLL-1 and TLL-2 are considered as promising drug targets for the
      treatment of excessive fibrosis and muscle wasting. We report here the crystal
      structures of the protease domains of human BMP-1 and the closely related Tolloid
      like protease 1 (TLL-1). The crystal structures reveal an unexpected conformation
      of a cysteine-rich loop within the active site, and suggest that a flap movement
      is required in order to allow substrate binding. On the basis of these
      substantial differences between the BMP-1 and astacin active sites, a structural
      basis for their differing substrate specificities is proposed.

PMID- 18824174
TI  - Three-dimensional structures of Pseudomonas aeruginosa PvcA and PvcB, two
      proteins involved in the synthesis of 2-isocyano-6,7-dihydroxycoumarin.
AB  - The pvcABCD operon of Pseudomonas aeruginosa encodes four proteins (PA2254,
      PA2255, PA2256, and PA2257) that form a cluster that is responsible for the
      synthesis of a cyclized isocyano derivative of tyrosine. These proteins, which
      were identified originally as being responsible for a step in the maturation of
      the chromophore of the peptide siderophore pyoverdine, have been identified
      recently as belonging to a family of proteins that produce small organic
      isonitriles. We report that strains harboring a disruption in the pvcA or pvcB
      genes are able to grow in iron-depleted conditions and to produce pyoverdine.
      Additionally, we have determined the three-dimensional crystal structures of PvcA
      and PvcB. The structure of PvcA demonstrates a novel enzyme architecture that is
      built upon a Rossmann fold. We have analyzed the sequence conservation of enzymes
      within this family and identified six conserved motifs. These regions of the
      protein cluster around a putative active site cavity. The structure of the PvcB
      protein confirms it is a member of the Fe2+/alpha-ketoglutarate-dependent
      oxygenase family of enzymes. The active site of PvcB is compared to the
      structures of other family members and suggests that a conformational change to
      order several loops will accompany the binding of ligands.

PMID- 18824175
TI  - Evidence for the oligomeric state of 'elastic' titin in muscle sarcomeres.
AB  - The giant protein titin has important roles in muscle sarcomere integrity,
      elasticity and contractile activity. The key role in elasticity was highlighted
      in recent years by single-molecule mechanical studies, which showed a direct
      relationship between the non-uniform structure of titin and the hierarchical
      mechanism of its force-extension behavior. Further advances in understanding
      mechanisms controlling sarcomere structure and elasticity require detailed
      knowledge of titin arrangement and interactions in situ. Here we present data on
      the structure and self-interactive properties of an approximately 290 kDa (
      approximately 100 nm long) tryptic fragment from the I-band part of titin that is
      extensible in situ. The fragment includes the conserved 'distal' tandem Ig
      segment of the molecule and forms side-by-side oligomers with distinctive 4 nm
      cross-striations. Comparisons between these oligomers and the end filaments seen
      at the tips of native thick filaments indicate identical structure. This shows
      that end-filaments are formed by the elastic parts of six titin molecules
      connecting each end of the thick filament to the Z-line. Self-association of
      elastic titin into stiff end-filaments adds a further hierarchical level in the
      mechanism of titin extensibility in muscle cells. Self-association of this part
      of titin may be required to prevent interference of the individual flexible
      molecules with myosin cross-bridges interacting with actin.

PMID- 18824176
TI  - One-hit stochastic decline in a mechanochemical model of cytoskeleton-induced
      neuron death III: diffusion pulse death zones.
AB  - This is the third of three papers in which we study a mathematical model of
      cytoskeleton-induced neuron death. In the first two papers of this suite
      [Lomasko, T., Clarke, G., Lumsden, C., 2007a. One-hit stochastic decline in a
      mechanochemical model of cytoskeleton-induced neuron death I: cell fate arrival
      times. J. Theor. Biol. 249, 1-17, doi:10.1016/j.jtbi.2007.05.031; Lomasko, T.,
      Clarke, G., Lumsden, C., 2007b. One-hit stochastic decline in a mechanochemical
      model of cytoskeleton-induced neuron death II: transition state metastability. J.
      Theor. Biol. 249, 18-28, doi:10.1016/j.jtbi.2007.05.032], we established that the
      mean-field limit of our model relates the known patterns of neuron decline to
      specific scales of cytoskeleton reorganization and cell-cell interaction by
      diffusible death factors. In the mean-field limit, the spatially variable
      concentration of diffusing death factor is replaced by a constant average value.
      Recent empirical advances now permit the actual diffusion of such factors to be
      followed in intact neuropil. In this paper we therefore extend the model beyond
      the mean-field limit, to include the diffusion dynamics of death factor bursts
      released from dying neurons. A range of novel tissue degeneration patterns is
      observed, for which we confirm and extend the mean-field prediction that
      sigmoidal patterns of neuron population decay are a principal hallmark of cell
      death in the presence of death factor release.

PMID- 18824177
TI  - Pioglitazone acutely stimulates adiponectin secretion from mouse and human
      adipocytes via activation of the phosphatidylinositol 3'-kinase.
AB  - AIMS: Thiazolidinediones increase circulating adiponectin. We have previously
      demonstrated the involvement of the phosphatidylinositol 3-kinase (PI3K)
      signaling pathway in insulin-stimulated adiponectin secretion. We therefore
      investigated the effects of the thiazolidinedione pioglitazone on acute
      adiponectin secretion, and the involvement of the PI3K signaling pathway in this
      action. MAIN METHODS: We treated murine 3T3-L1 and human primary adipocytes with
      1-10 uM pioglitazone for 2 h, +/-PI3K inhibition by Wortmannin (WT). Secreted
      adiponectin was measured by Western blot. PI3K activity following 15-minute
      treatments with 1-10 uM pioglitazone was measured by thin layer chromatography.
      Pioglitazone's effect on adiponectin synthesis and on secretion of newly
      synthesized adiponectin was studied in 3T3-L1 adipocytes using a pulse-chase
      technique. KEY FINDINGS: Pioglitazone was found to increase adiponectin secretion
      and PI3K activity in a dose-dependent manner from 3T3-L1 and human adipocytes. In
      3T3-L1 adipocytes, 10 uM pioglitazone increased adiponectin secretion by 84+/-14%
      (p<0.0001) at 2 h. Similarly, in human adipocytes there was a 56+/-18% (p<0.02)
      increase in secretion. WT blocked the pioglitazone effect and decreased
      adiponectin secretion at 2 h (47% of pioglitazone treated, p<0.006). Pioglitazone
      increased PI3K activity in a dose-dependent manner in both 3T3-L1 (1.7 vs. 2.7
      fold increase over control at 2 uM vs. 10 uM dose, p=0.02) and human adipocytes.
      SIGNIFICANCE: Our data show that pioglitazone acutely stimulates adiponectin
      secretion from both 3T3-L1 and human adipocytes. This acute effect of
      pioglitazone is PI3K-dependent.

PMID- 18824178
TI  - Proteomic identification of haptoglobin as a stroke plasma biomarker in
      spontaneously hypertensive stroke-prone rats.
AB  - AIMS: We investigated changes in the expression of plasma proteins in
      spontaneously hypertensive stroke-prone rats (SHRSP) to identify stroke
      biomarkers. MAIN METHODS AND KEY FINDINGS: The present analysis using surface
      enhanced laser desorption/ionization time of flight mass spectrometry (SELDI-TOF
      MS) demonstrated that three peaks at mass/charge ratios (m/z) of 9330, 9480 and
      9700 decreased in intensity during the development and progression of
      hypertensive stroke in SHRSPs, but not in age-matched control SHR and Wistar
      rats. Administration of verapamil, an L-type calcium channel blocker which was
      effective for hypertension in SHRSP rats, prevented the decrease in plasma
      protein expression. A candidate biomarker protein (m/z 9330) was identified using
      LC-MS/MS as haptoglobin (Hp). Immunoblotting with anti-Hp antibody demonstrated
      the decreased expression of both Hpalpha and Hpbeta chains in SHRSP. In contrast,
      haptoglobin mRNA expression in the liver of SHRSPs slightly increased as compared
      with control rats. SIGNIFICANCE: These findings suggest that Hp is a biomarker
      candidate for discriminating pathogenic alterations of stroke.

PMID- 18824179
TI  - Homotopy methods for counting reaction network equilibria.
AB  - Dynamical system models of complex biochemical reaction networks are usually high
      dimensional, non-linear, and contain many unknown parameters. In some cases the
      reaction network structure dictates that positive equilibria must be unique for
      all values of the parameters in the model. In other cases multiple equilibria
      exist if and only if special relationships between these parameters are
      satisfied. We describe methods based on homotopy invariance of degree which allow
      us to determine the number of equilibria for complex biochemical reaction
      networks and how this number depends on parameters in the model.

PMID- 18824180
TI  - Fetal-juvenile origins of point mutations in the adult human tracheal-bronchial
      epithelium: absence of detectable effects of age, gender or smoking status.
AB  - Allele-specific mismatch amplification mutation assays (MAMA) of anatomically
      distinct sectors of the upper bronchial tracts of nine nonsmokers revealed many
      numerically dispersed clusters of the point mutations C742T, G746T, G747T of the
      TP53 gene, G35T of the KRAS gene and G508A of the HPRT1 gene. Assays of these
      five mutations in six smokers have yielded quantitatively similar results. One
      hundred and eighty four micro-anatomical sectors of 0.5-6x10(6) tracheal
      bronchial epithelial cells represented en toto the equivalent of approximately
      1.7 human smokers' bronchial trees to the fifth bifurcation. Statistically
      significant mutant copy numbers above the 95% upper confidence limits of
      historical background controls were found in 198 of 425 sector assays. No
      significant differences (P=0.1) for negative sector fractions, mutant fractions,
      distributions of mutant cluster size or anatomical positions were observed for
      smoking status, gender or age (38-76 year). Based on the modal cluster size of
      mitochondrial point mutants, the size of the adult bronchial epithelial
      maintenance turnover unit was estimated to be about 32 cells. When data from all
      15 lungs were combined the log2 of nuclear mutant cluster size plotted against
      log2 of the number of clusters of a given cluster size displayed a slope of
      approximately 1.1 over a range of cluster sizes from approximately 2(6) to 2(15)
      mutant copies. A parsimonious interpretation of these nuclear and previously
      reported data for lung epithelial mitochondrial point mutant clusters is that
      they arose from mutations in stem cells at a high but constant rate per stem cell
      doubling during at least ten stem cell doublings of the later fetal-juvenile
      period. The upper and lower decile range of summed point mutant fractions among
      lungs was about 7.5-fold, suggesting an important source of stratification in the
      population with regard to risk of tumor initiation.

PMID- 18824181
TI  - Studies on modulation of DNA integrity in Fenton's system by phytochemicals.
AB  - Chronic exposure to oxidative stress especially to highly reactive hydroxyl
      radicals (HO*) could damage biomolecules, particularly DNA, that in turn would
      accelerate onset of degenerative diseases. In the present study a few standard
      phytochemicals (vitamin C, gallic acid, catechin, apigenin, naringenin and
      naringin) and plant extracts (Hippophae rhamnoides kernel (HRK), Syzygium cumini
      kernel (SCK) and Punica granatum pericarp (PGP)) were evaluated for their
      potential to protect/damage DNA in Fenton's system using in vitro models. The
      results indicated a significant DNA protective effect for naringin and PGP
      whereas other phytochemicals/extracts showed DNA damaging effect similar to or
      more than that of control value. The phytochemicals/extracts were also evaluated
      for their antioxidant and iron chelation properties. In general, the
      phytochemicals/extracts with high antioxidant activity but without iron chelation
      capacity failed to protect DNA in Fenton's system, suggesting that iron chelation
      was an essential requirement for the phytochemicals studied here to retard HO*
      generation by Fenton's reaction. This was demonstrated by the high iron chelation
      capacity of naringin and PGP (83.67% and 68.67% respectively) and their DNA
      protective effect. Commonly consumed phytochemicals such as vitamin C and gallic
      acid with their high reducing power and at higher physiological concentration,
      could regenerate free iron for Fenton's reaction leading to DNA damage as shown
      here.

PMID- 18824182
TI  - Functional mutations in mouse norepinephrine transporter reduce sensitivity to
      cocaine inhibition.
AB  - The transporters of dopamine, norepinephrine and serotonin are molecular targets
      of cocaine, amphetamine, and therapeutic antidepressants. The residues involved
      in binding these drugs are unknown. We have performed several rounds of random
      and site-directed mutagenesis in the mouse norepinephrine transporter and
      screened for mutants with altered sensitivity to cocaine inhibition of substrate
      uptake. We have identified a triple mutation that retains close to wild-type
      transport function but displays a 37-fold decrease in cocaine sensitivity and 24
      fold decrease in desipramine sensitivity. In contrast, the mutant's sensitivities
      to amphetamine, methamphetamine, and methylphenidate are only slightly changed.
      Our data reveal critical residues contributing to the potent uptake inhibitions
      by these important drugs. Furthermore, this drug-resistant triple mutant can be
      used to generate a unique knock-in mouse line to study the role of norepinephrine
      transporter in the addictive effects of cocaine and the therapeutic effects of
      desipramine.

PMID- 18824183
TI  - Impaired relational organization of propositions, but intact transitive
      inference, in aging: Implications for understanding underlying neural integrity.
AB  - The ability to perform relational proposition-based reasoning was assessed in
      younger and older adults using the transitive inference task in which subjects
      learned a series of premise pairs (A>B, B>C, C>D, D>E, E>F) and were asked to
      make inference judgments (B?D, B?E, C?E). Learning of premise pairs was related
      to subsequent inference performance and conscious awareness of the stimulus
      hierarchy (A>B>C>D>E>F). Despite extended training, age-related deficits were
      observed for response times, accurate learning of the premise pairs, making
      inference judgments, and articulating the hierarchy. When performance for younger
      and older adults was examined with respect to whether they were subsequently
      considered aware of the hierarchy, older and younger adults still significantly
      differed on their accuracy for studied premise pairs, but performance between the
      age groups was similar for the inference pairs. Successful transitive inference
      performance is contingent upon the relational organization of propositions within
      memory and such processes are impaired in aging, potentially leading to
      disruptions in conscious access to the stimulus hierarchy. Such findings, in
      concert with previous neuropsychological and neuroimaging studies, implicate an
      age-related deficit in the functioning of frontal and medial temporal lobe
      structures, with particular emphasis on the hippocampus.

PMID- 18824184
TI  - Visual stimuli can impair auditory processing in cochlear implant users.
AB  - It has been shown that visual stimulation can activate cortical regions normally
      devoted to auditory processing in deaf individuals. This neural activity can
      persist even when audition is restored through the implantation of a cochlear
      implant, raising the possibility that cross-modal plasticity can be detrimental
      to auditory performance in cochlear implant users. To determine the influence of
      visual information on auditory performance after restoration of hearing in deaf
      individuals, the ability to segregate conflicting auditory and visual information
      was assessed in fourteen cochlear implant users with varied degree of expertise
      and an equal number of participants with normal-hearing matched for gender, age
      and hearing performance. An auditory speech recognition task was administered in
      the presence of three incongruent visual stimuli (color-shift, random-dot motion
      and lip movement). For proficient cochlear implant users, auditory performance
      was equal to that of controls in the three experimental conditions where visual
      stimuli were presented simultaneously with auditory information. For non
      proficient cochlear implant users, performance did not differ from that of
      matched controls when the auditory stimulus was paired with a visual stimulus
      that was color-shifted. However, significant differences were observed between
      the non-proficient cochlear implant users and their matched controls when the
      accompanying visual stimuli consisted of a moving random-dot pattern or
      incongruent lip movements. These findings raise several questions with regards to
      the rehabilitation of cochlear implant users.

PMID- 18824186
TI  - The role of androgens in the mediation of seasonal territorial aggression in male
      Siberian hamsters (Phodopus sungorus).
AB  - Testosterone (T) mediates aggression in a wide range of species. In some species,
      however, aggressive behavior persists or increases during the non-breeding season
      when T levels are relatively low. Animals that do not display a positive
      correlation between aggression and gonadal steroids suggest the need for further
      investigation of alternative neuroendocrine mechanisms mediating seasonal
      aggression. Siberian hamsters (Phodopus sungorus) are an ideal study system
      because they display increased territorial aggression during the non-breeding
      season which may be independent of circulating T levels. The goals of the present
      study were to: 1) explore the role of T in the aggression of reproductive males,
      and 2) test the hypothesis that the adrenal steroid dehydroepiandrosterone (DHEA)
      acts as an endocrine regulator of seasonal aggression. In Experiment 1,
      individuals were housed in long day (breeding) photoperiod and received
      castrations, exogenous T capsules or both manipulations. In Experiment 2, animals
      were housed in either long or short days (non-breeding) photoperiod and received
      DHEA or empty capsules. In both experiments, serum hormone levels and aggressive
      behavior were assessed. In Experiment 1, castration did not reduce aggression
      whereas exogenous T actually inhibited aggressive behavior. In Experiment 2,
      short-day individuals were more aggressive than long-day animals but DHEA
      treatment did not affect aggressive behavior, regardless of photoperiod. The
      present study supports the hypothesis that circulating gonadal steroids are not
      necessary to activate aggressive behavior in adult male hamsters. Further,
      seasonal changes in territorial aggression appear independent of circulating
      levels of DHEA in Siberian hamsters.

PMID- 18824185
TI  - Genetic influences on handedness: data from 25,732 Australian and Dutch twin
      families.
AB  - Handedness refers to a consistent asymmetry in skill or preferential use between
      the hands and is related to lateralization within the brain of other functions
      such as language. Previous twin studies of handedness have yielded inconsistent
      results resulting from a general lack of statistical power to find significant
      effects. Here we present analyses from a large international collaborative study
      of handedness (assessed by writing/drawing or self report) in Australian and
      Dutch twins and their siblings (54,270 individuals from 25,732 families). Maximum
      likelihood analyses incorporating the effects of known covariates (sex, year of
      birth and birth weight) revealed no evidence of hormonal transfer, mirror imaging
      or twin specific effects. There were also no differences in prevalence between
      zygosity groups or between twins and their singleton siblings. Consistent with
      previous meta-analyses, additive genetic effects accounted for about a quarter
      (23.64%) of the variance (95%CI 20.17, 27.09%) with the remainder accounted for
      by non-shared environmental influences. The implications of these findings for
      handedness both as a primary phenotype and as a covariate in linkage and
      association analyses are discussed.

PMID- 18824187
TI  - Spatial learning and memory in African mole-rats: the role of sociality and sex.
AB  - Spatial learning and memory is an important skill for the survival and fitness
      and may vary between the sexes depending on differences in space use. This is
      particularly true for animals that explore the subterranean niche as it is
      associated with high travelling costs. In subterranean rodents the complexity of
      burrow systems varies with differing degrees of sociality possibly posing
      stronger selective pressures regarding spatial abilities on species with more
      complex burrow structures. This could lead to superior abilities in spatial
      learning and memory in social compared to solitary subterranean species. We
      tested this hypothesis in two species of subterranean mole-rats, the eusocial
      Damaraland (Fukomys damarensis) and solitary Cape mole-rats (Georychus capensis)
      by comparing their ability to locate food in an artificial maze. Measurements of
      the time taken to the goal chamber, the number of wrong turns taken, and the
      average velocity at which animals travelled were used to compare performance
      between animals. We did not find marked sex-specific differences in either study
      species during the assessment of learning and memory retention. In accordance
      with our hypothesis significant differences between the species were apparent
      during both learning and memory trials with the social species exhibiting
      superior performances. However, in both species memory retention was generally
      high suggesting that the fossorial lifestyle poses a strong selective pressure on
      spatial abilities in subterranean mammals.

PMID- 18824188
TI  - Anti-estradiol-17beta single-chain Fv fragments: Generation, characterization,
      gene randomization, and optimized phage display.
AB  - A single-chain Fv fragment (scFv) against estradiol-17beta (E(2)) was generated
      to begin the construction of a library of various mutated anti-steroid antibodies
      with an improved affinity and/or specificity. A hybridoma clone secreting a
      specific anti-E(2) antibody (Ab#E4-4) was established by the cell fusion using
      splenocytes from a mouse immunized with an immunogenic E(2)-carrier conjugate.
      DNA fragments encoding the variable heavy and light domains (V(H) and V(L)) of
      the Ab#E4-4 were cloned and combined to give the scFv gene fragment encoding the
      sequence 5'-V(H)-(GGGGS)(3)-V(L)-3'. Compared to the Ab#E4-4 Fab fragment,
      soluble scFv (scFv#E4-4) protein showed a similar affinity to E(2)
      (K(a)=8.6x10(7)M(-1)) and a similar cross-reaction profile. To further study the
      fundamentals for creating a comprehensive library of mutated scFvs, the scFvV(H)
      and V(L) genes were amplified using error-prone PCR conditions and the frequency
      and pattern of incorporated mutations were investigated. For this, regular Taq
      polymerase was used in the presence of unequal concentrations of dNTPs. At 1.0mM
      MnCl(2), the error frequency reached to 8.5% and 11% for the V(H) and V(L)
      respectively, although a significant transition/transversion bias was observed.
      ScFv#E4-4 and the mutated polyclonal scFvs were then displayed on filamentous
      phage under various packaging conditions. Cultivation of the transformed bacteria
      was more suitable at 25 degrees C than at higher temperatures for the packaging
      of scFv-bearing phagemid particles. Based on these experimental conditions, an
      scFv-displaying phage library, each scFv member in which has mutated
      complementarity-determining region (CDR) H2, H3, L1, and L3, was constructed. A
      soluble scFv clone (scFv#m1-e7) with a mutated amino acid (I-->V) in CDR L1,
      isolated from this library, showed threefold higher affinity (K(a)=2.6 x 10(8)M(
      1)) than that of scFv#4-4.

PMID- 18824189
TI  - Learning to identify near-threshold luminance-defined and contrast-defined
      letters in observers with amblyopia.
AB  - We assessed whether or not the sensitivity for identifying luminance-defined and
      contrast-defined letters improved with training in a group of amblyopic observers
      who have passed the critical period of development. In Experiment 1, we tracked
      the contrast threshold for identifying luminance-defined letters with training in
      a group of 11 amblyopic observers. Following training, six observers showed a
      reduction in thresholds, averaging 20%, for identifying luminance-defined
      letters. This improvement transferred extremely well to the untrained task of
      identifying contrast-defined letters (average improvement=38%) but did not
      transfer to an acuity measurement. Seven of the 11 observers were subsequently
      trained on identifying contrast-defined letters in Experiment 2. Following
      training, five of these seven observers demonstrated a further improvement,
      averaging 17%, for identifying contrast-defined letters. This improvement did not
      transfer to the untrained task of identifying luminance-defined letters. Our
      findings are consistent with predictions based on the locus of learning for first
      and second-order stimuli according to the filter-rectifier-filter model for
      second-order visual processing.

PMID- 18824190
TI  - Feature-based attention and the suppression of non-relevant object features.
AB  - Feature-directed attention has been recently studied in various psychophysical,
      electrophysiological, and imaging studies. Convincing evidence has been obtained
      for its global effectiveness, but there is a debate about the processing fate of
      non-attended target features. A number of studies demonstrated feature-directed
      attention being associated with co-selection of non-relevant object features,
      thus resulting in selection of the entire object, whereas most other studies did
      not examine the extent to which processing of non-attended features was affected.
      Here, we present the results of two psychophysical experiments consisting of a
      Posner-like paradigm in which subjects were cued either to an individual feature
      or the entire object. We measured reaction times to changes in speed or colour of
      one of two simultaneously presented gratings. Our results strongly support the
      view that feature-based selection is a unique selection process different from
      object-based selection in that it can be associated with active suppression of
      non-relevant features.

PMID- 18824191
TI  - Refractive index measurement of the isolated crystalline lens using optical
      coherence tomography.
AB  - An optical coherence tomography system has been developed that was designed
      specifically for imaging the isolated crystalline lens. Cross-sectional OCT
      images were recorded on 40 lenses from 32 human donors with an age range of 6-82
      years. A method has been developed to measure the axial thickness and average
      refractive index of the lens from a single recorded image. The measured average
      group refractive index at the measurement wavelength of 825 nm was converted to
      the average phase refractive index at 589 nm using lens dispersion data from the
      literature. The average refractive index for all lenses measured was 1.408+/
      0.005 which agrees well with recent MRI measurements of the lens index gradient.
      A linear regression of the data resulted in a statistically significant decrease
      in the average refractive index with age, but a simple linear model was
      insufficient to explain the age dependence. The results presented here suggest
      that the peak refractive index in the nucleus is closer to 1.420, rather than the
      previously accepted value of 1.406.

PMID- 18824192
TI  - Non-classical hydrogen bonds in interleukins: the role of C-H...O interactions.
AB  - The role of classical hydrogen bonds in the structural stability of biological
      macro-molecules is well understood. In the present study, we explore the
      influence of C-H...O interactions in relation to other environmental preferences
      in interleukins. Main chain-main chain interactions are predominant. Pro residues
      might stabilize helices and strands by C-H...O H-bonds in interleukins. Majority
      of the C-H...O interacting residues were solvent exposed. 62% of C-H...O
      interactions was long-range interactions. The results presented in this study
      might be useful for structural stability studies in interleukins.

PMID- 18824193
TI  - Defense system by mesenchyme cells in bipinnaria larvae of the starfish, Asterina
      pectinifera.
AB  - Here we characterize starfish larval mesenchyme cells, in terms of not only their
      phagocytic behavior, but also their structural and functional properties as a
      defense system. Our study reveals the following: (1) most mesenchyme cells
      construct a dynamic network structure beneath the body wall; (2) mesenchyme cells
      phagocytically respond to almost all foreign materials and form syncytial
      aggregates to conceal relatively large amounts and large sizes of foreign
      material; (3) the morphologies of the syncytial aggregates differ from one
      another depending on the species and the surface configuration of the cellular
      foreign material; (4) no mesenchyme cells respond to live mesenchyme cells even
      though they phagocytose chemically fixed cells; (5) mesenchyme cells phagocytose
      both cellular constituents effluxed from the ectodermal cells and foreign
      materials taken into the blastocoel through the body wall. Together, these
      results suggest that mesenchyme cells are equipped with a spectrum of abilities
      to engage in a defense system in starfish larva.

PMID- 18824194
TI  - Cholesterol in coronary heart disease and psychiatric disorders: same or opposite
      effects on morbidity risk?
AB  - The goal of this article is to review the studies that have linked low
      cholesterol levels with psychiatric symptoms or behavioral disorders in order to
      clarify which cholesterol fractions may influence psychological well being and
      mental health. The distinction between "bad" (i.e., pro-atherogenic) and "good"
      (i.e., anti-atherogenic) cholesterol is crucial to decide if the clinical
      benefits of low cholesterol levels for cardiovascular health might turn into a
      risk factor for psychiatric morbidity. Although the data from studies linking low
      cholesterol to aggression, suicide and self-harm, impulsivity, negative mood,
      postnatal depression, and cognitive dysfunction are far from unequivocal, the
      balance of evidence from new randomized controlled trials is reassuring. However,
      there are some subgroups of vulnerable individuals who, unlike the majority of
      persons in the general population, are susceptible to the psychological and
      behavioral adverse outcomes associated with low cholesterol levels. Because in
      some cases pro-atherogenic lipid and lipoprotein fractions are involved in this
      vulnerability, reaching the double goal of promoting both cardiovascular and
      mental health may be problematic for some individuals. A major task of future
      research is to identify these vulnerable individuals.

PMID- 18824195
TI  - Default-mode brain dysfunction in mental disorders: a systematic review.
AB  - In this review we are concerned specifically with the putative role of the
      default-mode network (DMN) in the pathophysiology of mental disorders. First, we
      define the DMN concept with regard to its neuro-anatomy, its functional
      organisation through low frequency neuronal oscillations, its relation to other
      recently discovered low frequency resting state networks, and the cognitive
      functions it is thought to serve. Second, we introduce methodological and
      analytical issues and challenges. Third, we describe putative mechanisms proposed
      to link DMN abnormalities and mental disorders. These include interference by
      network activity during task performance, altered patterns of antagonism between
      task specific and non-specific elements, altered connectively and integrity of
      the DMN, and altered psychological functions served by the network DMN. Fourth,
      we review the empirical literature systematically. We relate DMN dysfunction to
      dementia, schizophrenia, epilepsy, anxiety and depression, autism and attention
      deficit/hyperactivity disorder drawing out common and unique elements of the
      disorders. Finally, we provide an integrative overview and highlight important
      challenges and tasks for future research.

PMID- 18824196
TI  - PET measurement of changes in D2/D3 dopamine receptor binding in a nonhuman
      primate during chronic deep brain stimulation of the bed nucleus of the stria
      terminalis.
AB  - PET imaging is a powerful tool for measuring physiological changes in the brain
      during deep brain stimulation (DBS). In this work, we acquired five PET scans
      using a highly selective D2/D3 dopamine antagonist, 18F-fallypride, to track
      changes in dopamine receptor availability, as measured by the distribution volume
      ratio (DVR), through the course of DBS in the bed nucleus of the stria terminalis
      (BNST) in a nonhuman primate. METHODS: PET scans were performed on a rhesus
      monkey with unilateral BNST stimulation during periods of baseline, chronic high
      frequency (130 Hz) and low frequency (50 Hz) DBS stimulation, and during a
      washout period between stimulation periods. A final scan was performed with the
      electrode stimulation starting 110 min into the scan. Whole brain parametric
      images of (18)F-fallypride DVR were calculated for each condition to track
      changes in both striatal and extrastriatal D2/D3 availability. RESULTS: The
      monkey displayed significant increases in receptor binding throughout the brain
      during DBS relative to baseline for 130 and 50 Hz, with changes in DVR of:
      caudate 42%, 51%; putamen 56%, 57%; thalamus 33%, 49%; substantia nigra 29%, 26%;
      and prefrontal cortex 28%, 56%, respectively. Washout and post-stimulation scans
      revealed DVR values close to baseline values. Activating the stimulator midway
      through the final scan resulted in no statistically significant changes in
      binding. CONCLUSIONS: PET neuroligand imaging has demonstrated the sensitivity to
      track changes in dopamine D2/D3 binding during the course of DBS. These methods
      show great potential for providing insight into the neurochemical consequences of
      DBS.

PMID- 18824197
TI  - IDO: a double-edged sword for T(H)1/T(H)2 regulation.
AB  - Indoleamine 2,3-dioxygenase (IDO) has been well defined as one of the important
      immunosuppressive properties for T(H)1 cell-mediated immune responses, but its
      function in T(H)2 dominant system is poorly understood. Recently, an appreciable
      number of publications suggest that the role of IDO in T(H)2 cell regulation may
      be different from that of T(H)1 immune responses. Here we review the evidence on
      the regulatory function of IDO and tryptophan metabolites in T(H)1/T(H)2
      differentiation. We propose that IDO-kynurenine pathway can serve as a negative
      feedback loop for T(H)1 cells but it may play a distinct role in up-regulating
      T(H)2 dominant immune responses.

PMID- 18824198
TI  - Antibodies to myelin oligodendrocyte glycoprotein are not involved in the
      severity of chronic non-remitting experimental autoimmune encephalomyelitis.
AB  - To elucidate the role of antibodies in development of chronic non-remitting
      experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice, which is a well
      established Th1-mediated autoimmune disease, and the involvement of activation
      induced cytidine deaminase (AID) in Th1-mediated function, we have investigated
      the myelin oligodendrocyte glycoprotein (MOG)-induced EAE in mice deficient of
      AID, which is absolutely required for class switching and somatic hypermutation.
      Following immunization with MOG, AID(-/-) had completely same levels of clinical
      and pathological severity of EAE when compared with AID(+/-) and AID(+/+),
      although AID(-/-) did not produce IgG and anti-MOG IgG. Similar levels of T cell
      proliferation and a modest increase of anti-MOG IgM synthesis were found in
      spleen cells of AID(-/-) stimulated with MOG. These results indicate that
      antibodies are not involved in development of EAE in C57BL/6 mice.

PMID- 18824199
TI  - 6-Hydroxydopamine lesion in thalamic reticular nucleus reduces anxiety behaviour
      in the rat.
AB  - We have studied the effect of the lesion of the dopaminergic innervation of the
      thalamic reticular nucleus (TRn) on anxiety and motor behaviour. The lesion of
      the dopamine innervation was produced by the injection of 6-hydroxydopamine into
      the dorsal part of the thalamic reticular nucleus. The lesion decreased the
      number of TH (+) cells of the pars compacta of substantia nigra by 33%, without
      modifying the number of TH (+) cells in ventral tegmental area. The lesion
      increased the time spent by the rats on the open arms of the elevated plus maze
      and decreased the duration of burying in the shock-probe test. Both results
      suggest reduced anxiety. The loss of the dopamine innervation to the TRn
      decreased the number of rearings but did not significantly affect total motor
      activity, gait or motor coordination, as evidenced by rotarod performance. These
      findings suggest that dopamine in the TRn plays a role in fear-related behaviour.

PMID- 18824200
TI  - Sympathetic nerve and cardiovascular responses to auditory startle and prepulse
      inhibition.
AB  - While sudden (startling) sensory stimuli are generally thought of as inducing
      sympathetic excitation, in humans there is a short-lasting inhibition of limb
      muscle sympathetic nerve activity (MSNA). This study is the first to examine and
      contrast the effects of acoustic startle and the prepulse inhibition of startle
      (PPI) on MSNA, blood pressure, heart rate, and eye blinks. Startle elicited a two
      component withdrawal of MSNA: an early inhibition of one sympathetic burst
      followed by a second inhibition. PPI abolished the early, but not the late MSNA
      inhibition. Prepulse stimuli alone had no early inhibitory effects on MSNA. Early
      MSNA inhibition, which may occur at latencies of approximately 100 ms, appears to
      be part of a CNS-generated startle reflex which subserves automatic defensive
      responses to potential threats. The late MSNA inhibition coincided with the
      stimulus-induced blood pressure increase and is probably an inhibitory reflex
      response.

PMID- 18824201
TI  - Neurophysiological indices of perceptual object priming in the absence of
      explicit recognition memory.
AB  - The aim of this study was to identify ERP correlates of perceptual object priming
      that are insensitive to factors affecting explicit, episodic memory. EEG was
      recorded from 21 participants while they performed a visual object recognition
      test on a combination of unstudied items and old items that were previously
      encountered during either a 'deep' or 'shallow' levels-of-processing (LOP) study
      task. The results demonstrated a midline P150 old/new effect which was sensitive
      only to objects' old/new status and not to the accuracy of recognition responses
      to old items, or to the LOP manipulation. Similar outcomes were observed for the
      subsequent P200 and N400 effects, the former of which had a parietal scalp
      maximum and the latter, a broadly distributed topography. In addition an LPC
      old/new effect typical of those reported in past ERP recognition studies was
      observed. These outcomes support the proposal that the P150 effect is reflective
      of perceptual object priming and moreover, provide novel evidence that this and
      the P200 effect are independent of explicit recognition memory process(es).

PMID- 18824202
TI  - Enterostatin reduces serum cholesterol levels by way of a CCK(1) receptor
      dependent mechanism.
AB  - Enterostatin (APGPR), an anorectic pentapeptide derived from the amino terminus
      of procolipase, significantly reduced serum cholesterol levels after oral
      administration at a dose of 100 mg/kg for 3 days in mice fed a high-cholesterol
      cholic acid diet. The hypocholesterolemic effect of APGPR was inhibited by
      pretreatment with lorglumide, an antagonist for cholecystokinin 1 (CCK(1))
      receptor, even though APGPR does not have any affinity for CCK(1) receptors.
      Similarly, the hypocholesterolemic activity of VPDPR, an APGPR analogue, was
      blocked by lorglumide. These results suggest that the hypocholesterolemic effects
      of APGPR and VPDPR are mediated by a CCK(1) receptor-dependent mechanism.

PMID- 18824203
TI  - Comparison of different doses of antigen for intradermal administration in pigs:
      the Actinobacillus pleuropneumoniae model.
AB  - The intensity of antibody responses and level of protection against challenge
      infection induced by Actinobacillus pleuropneumoniae (APP) were compared in
      piglets vaccinated intramuscularly with different vaccination doses of a subunit
      vaccine. Secondary antibody responses to APP exotoxins induced by the
      intradermally administered diluted vaccines did not differ from those induced by
      undiluted vaccines administered either intradermally or intramuscularly. The
      level of protection measured by the clinical course of challenge infection to the
      extent of lung lesions was significantly higher in animals vaccinated with a
      three-time diluted vaccine in comparison with animals that were administered
      intramuscularly or intradermally with the most concentrated or the most diluted
      vaccines.

PMID- 18824204
TI  - Special edition editorial celebrating 25 years of publication.

PMID- 18824205
TI  - Protective roles of onion and garlic extracts on cadmium-induced changes in sperm
      characteristics and testicular oxidative damage in rats.
AB  - Cadmium (Cd) is known to exert gonadotoxic and spermiotoxic effects. The present
      study was performed to assess the possible protective roles of onion (Allium cepa
      Linn) and garlic (Allium sativum Linn) extracts on Cd-induced testicular damage
      and spermiotoxicity. The control group received double distilled water; Cd group
      received Cd (1.5mg/100g BW/day) orally; extract-treated groups were pre-treated
      with varied doses of onion and/or garlic extract (0.5ml and 1.0ml/100g BW/day)
      orally for one week and then simultaneously challenged with Cd (1.5mg/100g
      BW/day) for additional three weeks. Testicular tissue oxidant/antioxidant status
      and sperm characteristics were determined. Cd caused a marked (p<0.001) rise in
      testicular lipid peroxidation (LPO) and glutathione S-transferase (GST) levels
      whereas glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and
      alkaline phosphatase (ALP) levels were decreased. Cd intoxication significantly
      (p<0.001) decreased epididymal sperm concentration and sperm progress motility,
      increased percent total sperm abnormalities and live/dead count. Both extracts
      successfully attenuated these adverse effects of Cd. Onion extract offers a dose
      dependent protection. Our study demonstrated that aqueous extracts of onion and
      garlic could proffer a measure of protection against Cd-induced testicular
      oxidative damage and spermiotoxicity by possibly reducing lipid peroxidation and
      increasing the antioxidant defence mechanism in rats.

PMID- 18824206
TI  - Analysis of urinary andrographolides and antioxidant status after oral
      administration of Andrographis paniculata leaf extract in rats.
AB  - A simple high-performance liquid chromatography (HPLC) method was developed to
      determine the content of andrographolide (AP) and 14-deoxy-11,12
      dideoxyandrographolide (DIAP) in a pooled urine of rat obtained within 24h after
      an oral dose of Andrographis paniculata leaf extract at 1g/kg body weight.
      Cumulative urinary excretion of AP and DIAP in 24h after oral administration of
      the extract was 0.88% and 1.61% of oral dose administered, respectively. The
      extract showed significant reduction (p<0.05) of MDA levels and elevation of
      total antioxidant status in rat urine samples collected in 24 after oral
      administration.

PMID- 18824207
TI  - The influence of gaseous ozone and ozonated water on microbial flora and
      degradation of aflatoxin B(1) in dried figs.
AB  - In this study, the effectiveness of gaseous ozone and ozonated water on microbial
      flora and aflatoxin B(1) content of dried figs were investigated. After dried
      figs were exposed to13.8mgL(-1) ozone gas and 1.7mgL(-1) ozonated water for 7.5,
      15 and 30min, variation of aerobic mesophilic bacteria (AMB), E. coli, coliform,
      yeast and mold counts were determined. Before and after ozone treatments molds on
      dried figs were also isolated and identified. In both ozone treatments, AMB was
      not exactly inactivated whereas E. coli was completely destroyed at 7.5min.
      Coliform, and yeast were also destroyed at 7.5 and 15min in ozonated water,
      respectively. Ozone applications at 15min were sufficient for inactivation of all
      molds. Aspergillus flavus and Aspergillus parasiticus which cause aflatoxin
      formation were isolated from dried figs. Artificially contaminated with aflatoxin
      B(1) samples were also treated with gaseous ozone and ozonated water for 30, 60
      and 180min, respectively. In both of treatments, degradation of aflatoxin B(1)
      was increased due to increasing of ozonation time. Results indicated that gaseous
      ozone was more effective than ozonated water for reduction of aflatoxin B(1),
      whereas ozonated water was affected for decreasing microbial counts.

PMID- 18824208
TI  - Protective effects of selenium (Se) and zinc (Zn) on cadmium (Cd) toxicity in the
      liver and kidney of the rat: histology and Cd accumulation.
AB  - To assess the co-effect of Se and Zn on Cd accumulation in the liver and kidney
      and on their histology, male rats were exposed either to Cd, Cd+Zn, Cd+Se, or
      Cd+Zn+Se in their drinking water, during 35 days. Exposure to Cd resulted in its
      accumulation in the liver and kidney. In the Cd-Zn and Cd-Zn-Se groups, Cd
      contents in the two organs were significantly (p < 0.01) higher than those in the
      Cd group. Se did not induce any significant difference in hepatic and renal
      concentrations of Cd in comparison to Cd-treated group. Light microscopic
      examination indicated severe histological changes in the two organs under Cd
      influence. Se or Zn partially alleviated the damage observed in the liver. The
      same effect was remarked in the kidney with Se, but no differences in the renal
      histological structure have been observed between the Zn-Cd and the control
      groups. With Se and Zn simultaneous treatment during Cd exposure, the observed
      morphological changes had practically disappeared from the liver, but were only
      reduced in the kidney. CONCLUSION: Se and Zn can have a cooperative effect in the
      protection against Cd-induced structural damage in the liver but not in the
      kidney.

PMID- 18824209
TI  - A matrix assisted laser desorption ionization time-of-flight mass spectrometry
      investigation to assess the composition of cod liver oil based products which
      displayed a different in vivo allergenic power.
AB  - Cod liver oil is a well-known "nutraceutical", which contains a wide range of
      substances, including triacylglycerols (TAGs), mono- and di-acylglycerols, free
      fatty acids, vitamins and n-3 polyunsaturated fatty acids. Topically applied, cod
      liver oil contributes to faster wound healing and improvement in skin quality. We
      recently reported a case of allergic contact dermatitis to cod liver oil
      contained in a topical ointment, in whom the patch test reaction with the
      ointment containing cod liver oil at a concentration of 40% was stronger than the
      reaction induced by a pure cod liver oil at the same concentration. We
      hypothesized that the different reactivity could be explained by differences in
      composition of the two products. In order to verify this hypothesis, we assessed
      the composition of those products using a matrix-assisted laser desorption
      ionization time-of-flight mass spectrometry (MALDI-TOF-MS). The results obtained
      showed that the spectra of the ointment and of the cod liver oil samples were
      very similar, even if a major number of peaks were observable in the higher mass
      range of the spectra relevant to the analysis of the ointment sample, that have
      been assigned to higher molecular weight TAGs. Our results suggest that the
      different reactivity to the two products could be due to differences in the
      amount of contained TAGs. TAGs may favor the penetration of the allergen(s) or
      may be the direct culprit substances, taking into account that TAGs have been
      reported to have sensitizing properties.

PMID- 18824210
TI  - Effects of combustion-derived ultrafine particles and manufactured nanoparticles
      on heart cells in vitro.
AB  - Evidence from epidemiological studies indicates that acute exposure to airborne
      pollutants is associated with an increased risk of morbidity and mortality
      attributed to cardiovascular diseases. The present study investigated the effects
      of combustion-derived ultrafine particles (diesel exhaust particles) as well as
      engineered nanoparticles (titanium dioxide and single-walled carbon nanotubes) on
      impulse conduction characteristics, myofibrillar structure and the formation of
      reactive oxygen species in patterned growth strands of neonatal rat ventricular
      cardiomyocytes in vitro. Diesel exhaust particles as well as titanium dioxide
      nanoparticles showed the most pronounced effects. We observed a dose-dependent
      change in heart cell function, an increase in reactive oxygen species and, for
      titanium dioxide, we also found a less organized myofibrillar structure. The
      mildest effects were observed for single-walled carbon nanotubes, for which no
      clear dose-dependent alterations of theta and dV/dt(max) could be determined. In
      addition, there was no increase in oxidative stress and no change in the
      myofibrillar structure. These results suggest that diesel exhaust as well as
      titanium dioxide particles and to a lesser extent also single-walled carbon
      nanotubes can directly induce cardiac cell damage and can affect the function of
      the cells.

PMID- 18824211
TI  - Driving GDNF expression: the green and the red traffic lights.
AB  - Glial cell line-derived neurotrophic factor (GDNF) is widely recognized as a
      potent survival factor for dopaminergic neurons of the nigrostriatal pathway that
      degenerate in Parkinson's disease (PD). In animal models of PD, GDNF delivery to
      the striatum or the substantia nigra protects dopaminergic neurons against
      subsequent toxin-induced injury and rescues previously damaged neurons, promoting
      recovery of the motor function. Thus, GDNF was proposed as a potential therapy to
      PD aimed at slowing down, halting or reversing neurodegeneration, an issue
      addressed in previous reviews. However, the use of GDNF as a therapeutic agent
      for PD is hampered by the difficulty in delivering it to the brain. Another
      potential strategy is to stimulate the endogenous expression of GDNF, but in
      order to do that we need to understand how GDNF expression is regulated. The aim
      of this review is to do a comprehensive analysis of the state of the art on the
      control of endogenous GDNF expression in the nervous system, focusing mainly on
      the nigrostriatal pathway. We address the control of GDNF expression during
      development, in the adult brain and after injury, and how damaged neurons signal
      glial cells to up-regulate GDNF. Pharmacological agents or natural molecules that
      increase GDNF expression and show neuroprotective activity in animal models of PD
      are reviewed. We also provide an integrated overview of the signalling pathways
      linking receptors for these molecules to the induction of GDNF gene, which might
      also become targets for neuroprotective therapies in PD.

PMID- 18824212
TI  - Frontal-midline theta from the perspective of hippocampal "theta".
AB  - Electrical recordings from the surface of the skull have a wide range of rhythmic
      components. A major task of analysis of this EEG is to determine their source and
      functional significance. The hippocampal "theta rhythm" has been extensively
      studied in rats and its rhythmicity has recently been shown to be functionally
      significant, per se. Here, we use relevant aspects of the hippocampal literature
      to provide perspective on one of the most studied human EEG rhythms: frontal
      midline theta. We review its electrographic features, localization, prevalence,
      age distribution, behavioural modulation (particularly in relation to working
      memory, spatial navigation, episodic memory, internalised attention and
      meditation), relationship to personality, drug interactions, neurochemical
      relationships, and coherence with rhythmic activity at other sites. We conclude
      that FM-theta, like hippocampal theta, appears to play a role in (or at least
      occur during) processing of memory and emotion. It is correlated with working
      memory and/or sustained attention; but this does not entail a role in function
      since clear behavioural correlates of hippocampal theta have been demonstrated
      that are not sensitive to hippocampal damage. FM-theta is increased by anxiolytic
      drug action and personality-related reductions in anxiety, whereas hippocampal
      theta is decreased by anxiolytic drugs. In animals, frontal theta and hippocampal
      theta can be phase-locked or independent, depending on behavioural state. So, the
      cognitive functions of FM-theta, and their relationship to hippocampal theta, are
      unclear and definitive evidence for functional involvement in cognitive or
      emotional processing is lacking. One possible solution to this problem is
      analysis of FM-theta in animals-provided homology can be determined. The issues
      of sporadicity and low incidence of FM-theta also need to be addressed in the
      future. Changes in functional connectivity, indicated by changes in coherence,
      are also a largely untapped resource. We suggest that the most hopeful path to
      assessing the functions of FM-theta will be through the use of drugs, and the
      variation of their effects depending on baseline levels of FM-theta. Finally, we
      review some theories of theta function. Despite the apparent richness of the
      current data, we conclude that it is difficult (and may ultimately be impossible)
      to formulate a theory that attributes a specific cognitive function to FM-theta.
      However, the theories share some general computational assumptions and these
      should be a useful guide to future work and, ultimately, a definite theory of the
      function or functions of FM-theta.

PMID- 18824213
TI  - Multiple post-translational modifications of mouse insulin-like growth factor
      binding protein-6 expressed in epithelial Madin-Darby canine kidney cells.
AB  - Insulin-like growth factors (IGFs), IGF receptors and IGF binding proteins
      (IGFBPs) participate in the regulation of proliferation and differentiation of
      epithelial cells. Expression of the growth-inhibitory murine IGFBP-6 in
      epithelial Madin-Darby canine kidney (MDCK) cells followed by 2D analysis
      revealed the presence of multiple isoforms. Metabolic labelling experiments
      showed that several IGFBP-6 isoforms are modified by phosphate and sulfate
      groups. Expression analysis of mutant IGFBP-6 further demonstrated that serine
      residue 143 is O-glycosylated. Substitution of serine 143 by alanine did slightly
      reduce the preferential sorting of mIGFBP-6 to the apical site in MDCK cells
      grown on semipermeable filters. Both the presence of multiple and heterogeneously
      modified isoforms of murine IGFBP-6 in MDCK cells, and the preferential secretion
      of non-glycosylated IGFBP-6 mutants to the apical side suggest that the major
      apical sorting signal is the protein moiety.

PMID- 18824214
TI  - Activation of extracellular signal-regulated kinase (ERK) and induction of
      mitogen-activated protein kinase phosphatase 1 (MKP-1) by perifused thyrotropin
      releasing hormone (TRH) stimulation in rat pituitary GH3 cells.
AB  - We investigated the pattern of extracellular signal-regulated kinase (ERK)
      phosphorylation and the induction of mitogen-activated protein kinase phosphatase
      1 (MKP-1) by thyrotropin-releasing hormone (TRH) under various stimulation
      conditions in pituitary GH3 cells. In static culture, ERK activation by
      continuous TRH was maximal at 10 min and persisted for up to 60 min, with a
      return to the basal level by 2h. Stimulation with continuous TRH in perifused
      cells resulted in a similar level of ERK phosphorylation. MKP-1 was expressed 60
      min following either static or perifused, continuous TRH stimulation. When cells
      were stimulated with pulsatile TRH every 30 min, ERK activation was maximal at 10
      min and returned to its baseline level by 30 min. ERK was phosphorylated again
      with each subsequent pulse. Pulsatile TRH did not induce MKP-1. Prolactin
      promoter activity following continuous, static TRH stimulation was higher than
      that following perifused TRH stimulation. TRH at a frequency of one pulse every
      30 min increased prolactin promoter activity similar to that of perifused,
      continuous TRH stimulation. Additionally, changes in pulse frequency resulted in
      alterations in the level of prolactin promoter. Following static stimulation, a
      10 min exposure to TRH was sufficient to obtain full activation of the prolactin
      promoter. Additionally, a 5-10 min exposure of TRH was sufficient to maintain ERK
      activation. A single 5-min pulse of TRH stimulation resulted in low activation of
      the prolactin promoter. ERK activation was necessary for prolactin gene
      transcription; however, prolactin gene transcription is not entirely determined
      by the strength or duration of TRH-induced ERK activation.

PMID- 18824215
TI  - Intranasal administration of progesterone increases dopaminergic activity in
      amygdala and neostriatum of male rats.
AB  - We evaluated the effects of intranasal administration of progesterone (PROG) on
      the activity of dopaminergic neurons in the brain of anesthetized rats by means
      of microdialysis. Male Wistar rats were implanted with guide cannulae in the
      basolateral amygdala and neostriatum. Three to 5 days later, they were
      anesthetized with urethane, and dialysis probes were inserted. After a
      stabilization period of 2 h, four 30-min samples were collected. Thereafter, the
      treatment (0.5, 1.0 or 2.0 mg/kg of PROG dissolved in a viscous castor oil
      mixture, or vehicle) was applied into the nose in a volume of 10 microl (5 microl
      in each nostril). In other animals, an s.c. injection of PROG (1.0, 2.0 or 4.0
      mg/kg) or vehicle was given. Samples of both application ways were collected at
      30-min interval for 4 h after the treatment and immediately analyzed with high
      performance liquid chromatography and electrochemical detection. Intranasal
      administration of 2 mg/kg of PROG led to an immediate (within 30 min after the
      treatment) significant increase in the basolateral amygdala dopamine levels. In
      the neostriatum, the 2 mg/kg dose led to a delayed significant increase in
      dopamine. S.c. administration of 4 mg/kg of PROG was followed by a delayed
      significant increase in dopamine, both, in the basolateral amygdala and
      neostriatum, but smaller in magnitude in comparison to the intranasal treatment.
      This is the first study to demonstrate dopamine-enhancing effects of PROG, not
      only in the neostriatum, but also in the basolateral amygdala. Our results
      indicate that the intranasal route of administration of PROG is a more
      efficacious way for targeting the brain than the s.c. route.

PMID- 18824216
TI  - Evidence for a detrimental role of nitric oxide synthesized by endothelial nitric
      oxide synthase after peripheral nerve injury.
AB  - Physical injury to a nerve is the most common cause of acquired peripheral
      neuropathy. Identification of molecules involved in degenerative and regenerative
      processes is a key step toward development of therapeutic tools in order to
      accelerate motor, sensory and/or autonomic function recovery. We have studied the
      role of nitric oxide (NO) using as a model the severe crushing of a motor nerve
      in adult rats. This type of injury up-regulates the three isoforms of nitric
      oxide synthase (NOS) in the affected nerve. Chronic systemic inhibition of NOS
      accelerated the onset of functional muscle reinnervation evaluated by the
      recording of compound muscle action potential evoked by electrical stimulation of
      the injured nerve. Besides, it increased the number of back-labeled motoneurons
      by application, 2 days after injury, of a retrograde marker 10 mm distal to the
      crushing site. These effects were mimicked by chronic specific inhibition of the
      endothelial isoform of nitric oxide synthase (eNOS), but not by specific
      inhibitors of the neuronal or inducible isoform. Next, we intraneurally injected
      a replication-deficient adenoviral vector directing the expression of a dominant
      negative mutant of eNOS (Ad-TeNOS). A single injection of Ad-TeNOS on the day of
      crushing significantly accelerated functional recovery of neuromuscular junction
      and increased axonal regeneration. Moreover, Ad-TeNOS did not compromise
      motoneuron viability or stability of reestablished neuromuscular junctions. Taken
      together, these results suggest that NO of endothelial origin slows down muscle
      reinnervation by means of detrimental actions on axonal regeneration after
      peripheral nerve injury. These experiments identify eNOS as a potential
      therapeutic target for treatment of traumatic nerve injuries and highlight the
      potential of gene therapy in treating injuries of this type using viral vectors
      to suppress the activity of eNOS.

PMID- 18824217
TI  - Hippocampal place cell activity during chasing of a moving object associated with
      reward in rats.
AB  - Hippocampal place cells encode location of animals in the environment. However,
      it remains unknown whether the hippocampal place cells encode a continuously
      moving object in the environment. To investigate this topic, we analyzed the
      place cell activity of freely moving rats when a toy car was introduced into an
      arena. First, in a freely moving task without the car, the rats freely navigated
      inside the arena to earn an intracranial stimulation (ICS) reward for each 150 cm
      traveled. Second, they were divided into two groups and tested using two
      different tasks. In the car-dependent navigation (CDN) task, the car was placed
      inside the arena, and the rat received ICS if it chased and came within 20 cm of
      the car. In the car-independent navigation (CIN) task, the rat acquired ICS
      rewards if it traveled 150 cm regardless of its relation to the car. Place fields
      remapped more frequently in the CDN than the CIN tasks. In both the CDN and CIN
      tasks, the place cell activity inside the place fields displayed moderate tuning
      to the movement parameters of the rats and car, and the distance between the car
      and rats. However, tuning of the place cells to movement variables of the car was
      more selective in the CDN than the CIN tasks, while information regarding
      movement variables of the car represented by the place cell activity was larger
      in the CDN than the CIN task. These results indicated that place cell activity
      within the place fields represents not only an animal's own location but also the
      movement variables of another moving object if that object is associated with
      rewards. The present results provide new evidence that place cell activity
      conveys relevant information in a task even if this information is derived from
      other moving objects.

PMID- 18824218
TI  - Extracellular amino acid levels in the striatum of the dt(sz) mutant, a model of
      paroxysmal dystonia.
AB  - The pathophysiology of idiopathic dystonia is still unknown, but it is regarded
      as a basal ganglia disorder. Previous studies indicated an involvement of a
      striatal GABAergic disinhibition and a cortico-striatal glutamatergic
      overactivity in the manifestation of stress-inducible dystonic episodes in the
      dt(sz) hamster, a model of idiopathic paroxysmal dystonia. These investigations
      were carried out postmortem or in anesthetized animals. In the present study, in
      vivo microdialysis in conscious, freely-moving dt(sz) and non-dystonic control
      hamsters was used to examine the levels of GABA, aspartate, glutamate, glutamine,
      glycine and taurine in each animal during following conditions: (1) at baseline
      in the absence of dystonia, (2) during an episode of paroxysmal dystonia
      precipitated by stressful stimuli, (3) during a recovery period and (4) at
      baseline after complete recovery. In comparison to non-dystonic controls, which
      were treated in the same manner as the dystonic animals, no differences could be
      detected under basal conditions. The induction of a dystonic episode in mutant
      hamsters led to higher contents of glycine in these animals in comparison to
      stressed but non-dystonic controls. Significant changes of glycine levels within
      the animal groups were not detected. The levels of the excitatory amino acids
      glutamate, glutamine and aspartate as well as the levels of the inhibitory amino
      acids GABA and taurine did not differ between the animal groups or between the
      periods of measurement. The higher levels of glycine might contribute to the
      manifestation of paroxysmal dystonia in dt(sz) hamsters, although unaltered
      glutamate, glutamine and aspartate levels do not support the hypothesis of a
      critical involvement of a cortico-striatal overactivity. It seems that a
      deficiency of GABAergic interneurons, found by previous immunohistochemical
      examinations, does not lead to reduced extracellular GABA levels in the striatum.

PMID- 18824219
TI  - Analgesic effects of intrathecally administered 26RFa, an intrinsic agonist for
      GPR103, on formalin test and carrageenan test in rats.
AB  - GPR103 is known as an orphan G protein-coupled receptor. 26RFa and QRFP are
      endogenous ligands of GPR103. GPR103 mRNA has been reported to be highly
      expressed in the superficial layers of the entire spinal cord and a high density
      of 26RFa binding sites was observed in the superficial layers of the dorsal horn.
      In the present study, the effects of spinally applied 26RFa were tested in the
      rat. Intrathecal injection of 26RFa significantly decreased the frequency of
      agitation behaviors induced by paw formalin injection, and attenuated the level
      of mechanical allodynia induced by paw carrageenan injection, in a dose dependent
      manner at doses between 0.01 and 10 microg. Intrathecal injection of 26RFa had no
      effect in both the 52.5 degrees C hotplate test and the mechanical nociceptive
      test at doses between 0.1 and 10 microg. An immunohistochemical study revealed
      that GPR103-like immunoreactivity (LI) was observed in the superficial layers of
      spinal dorsal horn, that QRFP-LI was observed in the dorsal root ganglion and
      that intrathecal 26RFa suppressed the expression of Fos-LI induced by paw
      formalin injection in the superficial layers of the spinal dorsal horn. These
      data suggested that spinally applied 26RFa may modulate spinal sensitization
      induced by paw formalin injection or paw carrageenan injection.

PMID- 18824220
TI  - Congruence of zebrin II expression and functional zones defined by climbing fiber
      topography in the flocculus.
AB  - The cerebellum is organized into parasagittal zones with respect to the
      topography of climbing fiber (CF) afferents and the expression of molecular
      markers such as zebrin II. Zebrin is expressed by a subset of Purkinje cells that
      are distributed as a parasagittal array of immunopositive and immunonegative
      stripes. Several studies in rodents suggest that, in general, CFs to the zebrin
      negative stripes convey somatosensory information, whereas CFs to the zebrin
      positive stripes convey information from visual and other sensory systems. The
      pigeon flocculus consists of four pairs of zebrin+/- stripes (P4 +/- through P7
      +/-), however the CF input consists entirely of visual inputs. Thus, because the
      correspondence of zebrin expression and CF information must be different from
      that proposed for rodents, we investigated this relationship in the pigeon
      flocculus. Floccular Purkinje cells respond to patterns of optic flow resulting
      from self-rotation about one of two axes: either the vertical axis (zones 0 and
      2), or a horizontal axis (zones 1 and 3). Visual CF afferents projecting to the
      flocculus arise from the medial column of the inferior olive (mcIO). Zones 0 and
      2 receive input from the caudal mcIO, whereas zones 1 and 3 receive input from
      the rostral mcIO. We injected a fluorescent anterograde tracer into the rostral
      and/or caudal mcIO and visualized zebrin expression. There was a strict
      concordance between CF organization and zebrin labeling: caudal mcIO injections
      resulted in CFs in zebrin bands P4 +/- and P6 +/-, whereas rostral mcIO
      injections resulted in CFs in zebrin bands P5 +/- and P7 +/-. Thus, zebrin
      stripes P4 +/- and P6 +/- correspond to the vertical axis zones 0 and 2, whereas
      P5 +/- and P7 +/- correspond to the horizontal axis zones 1 and 3. This is the
      first explicit demonstration that a series of zebrin stripes corresponds with
      functional zones in the cerebellum.

PMID- 18824221
TI  - Montanoa tomentosa glandular trichomes containing kaurenoic acids chemical
      profile and distribution.
AB  - Montanoa tomentosa has been used in traditional medicine in Mexico to treat
      diverse female health disorders; it is particularly useful in inducing
      childbirth. Microscopic analysis of leaf surfaces of M. tomentosa revealed the
      presence of glandular trichomes. The chemical profile and distribution of
      glandular trichomes from different developmental stages of M. tomentosa leaves
      were investigated. Two diterpenic acids, kaurenoic and grandiflorenic were
      detected in glandular trichomes through the glandular microsampling technique and
      GC/MS analysis. In the glandular trichomes of the leaves also up to twenty-six
      volatile terpenes were identified, where beta-eudesmol and valencene were the
      most abundant terpenes.

PMID- 18824222
TI  - The evolution of comparative cognition: is the snark still a boojum?
AB  - In "The Snark is a Boojum", Beach [Beach, F.A., 1950. The snark was a boojum.
      American Psychologist. 5, 115-124] famously asserted that animal psychology
      embraced too few species and too few problems to deserve the name comparative.
      Later in the 20th century, others [e.g. Kamil, A.C., 1988. A synthetic approach
      to the study of animal intelligence. In: Leger, D.W. (Ed.), Comparative
      Perspectives in Modern Psychology. Nebraska Symposium on Motivation, vol. 35.
      University of Nebraska Press, Lincoln, NE, pp. 230-257; Shettleworth, S.J., 1993.
      Where is the comparison in comparative cognition? Alternative research programs.
      Psychological Science. 4, 179-184] expressed similar concerns about the new
      subfield of comparative cognition, suggesting that a more biological approach to
      choice of species and problems was needed to balance a dominant anthropocentrism.
      The last 10-15 years have seen many new developments, and a recent survey like
      Beach's reveals a very different picture. Not only are many more species being
      studied, contributions by researchers from different backgrounds are increasing,
      and research on comparative cognition is better connected with developmental
      psychology, behavioral neuroscience, primatology, behavioral ecology, and other
      fields. Contemporary research addresses three major aspects of cognition about
      equally: basic processes, physical cognition, and social cognition. This article
      describes a selected research program from each area, chosen to exemplify current
      trends and challenges for the field.

PMID- 18824223
TI  - Cloning and expression analysis of some genes involved in the phosphoinositide
      and phospholipid signaling pathways from maize (Zea mays L.).
AB  - Previous studies have indicated the phosphoinositide and phospholipid signaling
      pathways play a key role in plant growth, development and responses to
      environmental stresses. However, little is known about the phosphoinositide and
      phospholipid signaling pathways in maize (Zea mays L.). To better understand the
      function of genes involved in the phosphoinositide and phospholipid signaling
      pathways in maize, the cDNA sequences of ZmPIS2, ZmPLC2, ZmDGK1, ZmDGK2 and
      ZmDGK3 were obtained by RACE (rapid amplification of cDNA ends) or in silico
      cloning combined with PCR. RT-PCR analysis of cDNA from five tissues (roots,
      stems, leaves, tassels, and ears) indicated that the expression patterns of the
      five cDNAs we isolated as well as ZmPIS, ZmPLC, ZmPLD varied in different
      tissues. To determine the effects of different environmental conditions such as
      cold, drought and various phytohormones (abscisic acid, indole-3-acetic acid and
      gibberellic acid) on gene expression, we analyzed expression by Real-Time (RT
      PCR), and found that the different isoforms of these gene families involved in
      the phosphoinositide and phospholipid signaling pathways have specific expression
      patterns. Our results suggested that these genes may be involved in the responses
      to environmental stresses, but have different functions. The isolation and
      analysis of expression patterns of genes involved in the phosphoinositide and
      phospholipid signaling pathways provides a good basis for further research of the
      phosphoinositide and phospholipid signaling pathways in maize and is a novel
      supplement to our comprehension of these pathways in plants.

PMID- 18824224
TI  - Molecular phylogeny and evolution of prosimians based on complete sequences of
      mitochondrial DNAs.
AB  - Prosimians (tarsiers and strepsirrhini) represent the basal lineages in primates
      and have a close bearing on the origin of primates. Although major lineages among
      anthropoidea (humans, apes and monkeys) are well represented by complete
      mitochondrial DNA (mtDNA) sequence data, only one complete mtDNA sequence from a
      representative of each of the infraorders in prosimians has been described until
      quite recently, and therefore we newly determined complete mtDNA sequences from 5
      lemurs, 4 lorises, one tarsier and one platyrrhini. These sequences were provided
      to phylogenetic analyses in combination with the sequences from the 15 primates
      species reported to the database. The position of tarsiers among primates could
      not be resolved by the maximum likelihood (ML) and neighbor-joining (NJ) analyses
      with several data sets. As to the position of tarsiers, any of the three
      alternative topologies (monophyly of haplorhini, monophyly of prosimians, and
      tarsiers being basal in primates) was not rejected at the significance level of
      5%, neither at the nucleotide nor at the amino acid level. In addition, the
      significant variations of C and T compositions were observed across primates
      species. Furthermore, we used AGY data sets for phylogenetic analyses in order to
      remove the effect of different C/T composition bias across species. The analyses
      of AGY data sets provided a medium support for the monophyly of haplorhini, which
      might have been screened by the variation in base composition of mtDNA across
      species. To estimates the speciation dates within primates, we analyzed the amino
      acid sequences of mt-proteins with a Bayesian method of Thorne and Kishino.
      Divergence dates were estimated as follows for the crown groups: about 35.4
      million years ago (mya) for lorisiformes, 55.3 mya for lemuriformes, 64.5 mya for
      strepsirrhini, 70.1 mya for haplorhini and 76.0 mya for primates. Furthermore, we
      reexamined the biogeographic scenarios which have been proposed for the origin of
      strepsirrhini (lemuriformes and lorisiformes) and for the dispersal of the
      lemuriformes and lorisiformes.

PMID- 18824225
TI  - In situ precipitation and vacuum drying of interferon alpha-2a: development of a
      single-step process for obtaining dry, stable protein formulation.
AB  - Feasibility studies were performed to develop a process for obtaining stable dry
      protein formulations based on in situ polyethylene glycol (PEG)-induced
      precipitation and vacuum drying of interferon alpha-2a (IFNalpha2a) solution in a
      vial. Using a laboratory scale freeze dryer, the process was carried out in two
      phases: first, protein solution containing PEG was concentrated to achieve
      protein precipitation, and second, remaining water was removed by further
      reducing the chamber pressure. Drying conditions, i.e. temperature and pressure,
      and solution composition were selected to ensure maximal precipitation
      (solubility of IFNalpha2a), to achieve precipitation without boiling, and to
      ensure stability. Dried formulations were subjected to stability studies (40
      degrees C). Concentration and precipitation could be achieved at a fast rate by
      utilizing pressures slightly above the vapor pressure of water. Fluorescence and
      circular dichroism (CD) studies showed that precipitated IFNalpha2a maintained
      its native structure. Fourier transform infrared spectroscopy (FTIR) studies
      showed that IFNalpha2a when dried in the presence of trehalose, maintained its
      secondary structure. Trehalose also prevented formation of aggregates during
      drying. Moisture contents of 1% (w/w) were achieved within 48 h of drying. Dry
      formulation containing 1:20:100 (w/w) IFNalpha2a:trehalose:mannitol was stable
      against aggregation and oxidation (6% oxidized at 40 degrees C, 6 months).
      Stability profile was comparable to a similar lyophilized formulation.

PMID- 18824226
TI  - Molecular imprinting within hydrogels II: progress and analysis of the field.
AB  - In the past decade, there has been an exponential increase in the number of
      papers describing molecular imprinting in hydrogels, a technique which creates
      memory for template molecules within a flexible macromolecular structure.
      Macromolecular memory or structural plasticity of polymer chains is a superior
      description of weakly crosslinked imprinted networks since significant
      flexibility can occur within the polymer chains. The focus of this article is to
      review and highlight work in the field describing the imprinting strategy within
      hydrogels and associated challenges, characterization methods of imprinted gels,
      current and potential translational applications, and future strategies and
      directions. This paper also describes ways to improve binding parameter efficacy
      and presents significant areas of opportunity to further describe, characterize,
      and understand imprinted gels. An analysis of the literature indicates that
      imprinting in hydrogels leads to significant improvements in template affinity,
      capacity, and selectivity over non-templated hydrogels for a number of templates
      such as ions, small and moderate molecular weight molecules, proteins, viruses,
      DNA, and cells. However, the influence of imprinting on the transport of template
      is much more complex, with little attention of most studies to structural
      analysis or discussion of the gel porosity/tortuosity in the control of template
      transport. Responsive, intelligent imprinted hydrogels are also highlighted that
      exhibit reversibly modulated template binding and transport. It is clear that
      this field has transitioned from infancy and is leading to breakthroughs in a
      number of areas such as controlled and modulated drug delivery, diagnostic
      sensors, and separation. For example in drug delivery, imprinting can lead to
      delayed transport and provides further control of therapeutic transport through
      the macromolecular structure as well as optimizes the number of therapeutic
      molecules to polymer chains.

PMID- 18824227
TI  - A comparison of the fit of flux through hairless mouse skin from water data to
      three model equations.
AB  - Data for the delivery of total species containing parent drugs from water through
      hairless mouse skin by prodrugs, logJ(MMAQ), has been fitted to the Roberts
      Sloan, RS, the Kasting-Smith-Cooper, KSC, and Magnusson-Anissimov-Cross-Roberts,
      MACR, equations. The RS model which contains a parameter for the dependence of
      flux on solubility in water, S(AQ), as well as solubility in the lipid isopropyl
      myristate, S(IPM), gave the best fit: logJ(MMAQ)=-2.30+0.575 logS(IPM)+0.425
      logS(AQ)-0.0016MW, r(2)=0.903. The values for the coefficients to the parameters
      are quite similar to those obtained when the RS model was fit to flux of solutes
      from water through human skin, logJ(MHAQ). There was no trend in predicting the
      under or over-performance of prodrugs based on their fit to the RS model and
      whether they were more or less soluble than their parent drugs. There was an
      inverse dependence of logJ(MMAQ) on partition coefficients or permeability
      coefficients similar to that observed for logJ(MHAQ). The similarities in trends
      for results for logJ(MMAQ) and logJ(MHAQ) suggests that design directives
      obtained from mouse skin can be extended to design new prodrugs or select new
      drugs for delivery through human skin.

PMID- 18824228
TI  - Molecular characterization of a novel cell surface ADP-ribosyl cyclase from the
      sea urchin.
AB  - The sea urchin is an extensively used model system for the study of calcium
      signalling by the messenger molecules NAADP and cyclic ADP-ribose. Both are
      synthesized by ADP-ribosyl cyclases but our molecular understanding of these
      enzymes in the sea urchin is limited. We have recently reported the cloning of an
      extended family of sea urchin ADP-ribosyl cyclases and shown that one of these
      enzymes (SpARC1) is active within the endoplasmic reticulum lumen. These studies
      suggest that production of messengers is compartmentalized. Here we characterize
      the properties of SpARC2. SpARC2 catalyzed both NAADP and cyclic ADP-ribose
      production. Unusually, the NAD surrogate, NGD was a poor substrate. In contrast
      to SpARC1, heterologously expressed SpARC2 localized to the plasma membrane via a
      glycosylphosphatidylinositol (GPI)-anchor. Transcripts for SpARC2 were readily
      detectable in sea urchin eggs and a majority of the endogenous membrane bound
      activity was found to be GPI-anchored. Our data reveal striking differences in
      the properties of sea urchin ADP-ribosyl cyclases and provide further evidence
      that messenger production may occur outside of the cytosol.

PMID- 18824229
TI  - Differential expression of the outer membrane protein W (OmpW) stress response in
      enterohemorrhagic Escherichia coli O157:H7 corresponds to the viable but non
      culturable state.
AB  - During an outbreak of enterohemorrhagic Escherichia coli (EHEC) O157, we showed
      previously that food isolates were resistant to oxidative stress, while patient
      isolates were sensitive to it. Because food isolates increased stress-sensitivity
      after mouse passage, this change most likely occurred during passage through
      patients. Here we demonstrate that the phenotypic change occurring during mouse
      passage correlates with the stress response of outer membrane protein W (OmpW) in
      EHEC O157 strains. Upon induction of oxidative stress, OmpW was highly expressed
      only in the stress-sensitive MP37 strain, obtained by mouse passage of food
      strain F2, but not in the F2 strain. Western blotting confirmed that expression
      of OmpW was induced in the viable but non-culturable (VBNC) state. Deletion of
      ompW in the MP37 strain increased recovery from dormancy, while overexpression of
      OmpW in the F2 strain decreased recovery when exposed to oxidative stress,
      suggesting that high levels of OmpW sensitize the bacteria to stress. DNA
      alignment revealed that the class I integron (int1I) fragments flanking the ompW
      gene are oriented in opposite directions between stress-resistant and -sensitive
      strains. All stress-sensitive strains induced ompW under stress. We propose that
      the different stress response of OmpW was introduced by genetic alteration during
      in vivo passage.

PMID- 18824230
TI  - The role of alemtuzumab in facilitating maintenance immunosuppression
      minimization following solid organ transplantation.
AB  - National registry data indicate a trend towards the incorporation of lymphocyte
      depletion antibody induction therapy into immunosuppressive regimens for solid
      organ transplantation. Depletional induction has been shown to reduce the risk of
      early acute rejection, but increase the risk of immune incompetence. As such, it
      recently has been paired with reduced maintenance immunosuppression in an effort
      to curb excessive immunosuppression without sacrificing low rejection rates.
      Alemtuzumab is a humanized CD52-specific monoclonal antibody that has been used
      in the setting of maintenance immunosuppression minimization. Although not
      specifically indicated for organ transplantation, it is now used off-label as an
      induction agent in approximately 10% of transplant recipients in the United
      States. In general, alemtuzumab is well tolerated and substantially reduces the
      risk of acute rejection in the first 6 months post-transplant in non-sensitized
      recipients. There is little evidence to support the notion that it uniquely
      promotes tolerance, and growing evidence that it is ineffective in the setting of
      allosensitization. Alemtuzumab-treated patients clearly remain dependent on
      maintenance immunosuppression. Long-term outcome data will be required to
      determine the magnitude and type of maintenance therapy that makes best use of
      alemtuzumab's depletional effects.

PMID- 18824231
TI  - Potentiation by cholinesterase inhibitors of cholinergic activity in rat isolated
      stomach and colon.
AB  - Acetylcholinesterase (AChE) inhibitors stimulate gastrointestinal (GI) motility
      and are potential treatments of conditions associated with inadequate GI
      motility. The ability of itopride to facilitate neuronally (predominantly
      cholinergic) mediated contractions of rat isolated stomach, evoked by electrical
      field stimulation (EFS), has been compared with other cholinesterase inhibitors
      and with tegaserod, a clinically effective prokinetic and non-selective 5-HT(4)
      receptor agonist which also facilitates GI cholinergic function. Neostigmine
      greatly increased EFS-evoked contractions over a narrow concentration range (0.01
      1 microM; 754+/-337% facilitation at 1 microM); higher concentrations (1, 3
      microM) also increased muscle tension. Donepezil increased EFS-evoked
      contractions gradually over the full range of concentrations (0.01-10 microM;
      maximum increase 516+/-20% at 10 microM). Itopride increased the contractions
      even more gradually, rising to 188+/-84% at 10 microM. The butyrylcholinesterase
      inhibitor iso-OMPA 0.01-10 microM also increased EFS-evoked contractions, to a
      maximum of 36+/-5.0% at 10 microM, similar to that caused by tegaserod (35+/-5.2%
      increase at 1 microM). The effects of tegaserod, but not itopride were inhibited
      by the 5-HT(4) receptor antagonist SB-204070A 0.3 microM. In rat isolated colon,
      neostigmine was again the most efficacious, causing a defined maximum increase in
      EFS-evoked contractions (343+/-82% at 10 microM), without changing muscle
      tension. Maximum increases caused by donepezil and itopride were, respectively,
      57.6+/-20 and 43+/-15% at 10 microM. These data indicate that the abilities of
      different AChE inhibitors to increase GI cholinergic activity differ markedly.
      Understanding the reasons is essential if AChE inhibitors are to be optimally
      developed as GI prokinetics.

PMID- 18824232
TI  - Mocr: a novel fusion tag for enhancing solubility that is compatible with
      structural biology applications.
AB  - A persistent problem in heterologous protein production is insolubility of the
      target protein when expressed to high level in the host cell. A widely employed
      strategy for overcoming this problem is the use of fusion tags. The best fusion
      tags promote solubility, may function as purification handles and either do not
      interfere with downstream applications or may be removed from the passenger
      protein preparation. A novel fusion tag is identified that meets these criteria.
      This fusion tag is a monomeric mutant of the Ocr protein (0.3 gene product) of
      bacteriophage T7. This fusion tag displays solubilizing activity with a variety
      of different passenger proteins. We show that it may be used as a purification
      handle similar to other fusion tags. Its small size and compact structure are
      compatible with its use in downstream applications of the passenger protein or it
      may be removed and purified away from the passenger protein. The use of monomeric
      Ocr (Mocr) as a complement to other fusion tags such as maltose-binding protein
      will provide greater flexibility in protein production and processing for a wide
      variety of protein applications.

PMID- 18824233
TI  - High-throughput T7 LIC vector for introducing C-terminal poly-histidine tags with
      variable lengths without extra sequences.
AB  - Immobilized metal ion affinity chromatography (IMAC) has become one of the most
      popular protein purification methods for recombinant proteins with a hexa
      histidine tag (His-tag) placed at the C- or N-terminus of proteins. Nevertheless,
      there are always difficult proteins that show weak binding to the metal chelating
      resin and thus low purity. These difficulties are often overcome by increasing
      the His-tag to 8 or 10 histidines. Despite their success, there are only few
      expression vectors available to easily clone and test different His-tag lengths.
      Therefore, we have modified Escherichia coli T7 expression vector pET21a to
      accommodate ligation-independent cloning (LIC) that will allow easy and efficient
      parallel cloning of target genes with different His-tag lengths using a single
      insert. Unlike most LIC vectors available commercially, our vectors will not
      translate unwanted extra sequences by engineering the N-terminal linker to anneal
      before the open reading frame, and the C-terminal linker to anneal as a His-tag.

PMID- 18824234
TI  - Single particle EM studies of the Drosophila melanogaster origin recognition
      complex and evidence for DNA wrapping.
AB  - Hyperphosphorylation of the Drosophila melanogaster origin recognition complex
      (DmORC) by cyclin dependent kinases (CDKs) allows nucleotide binding but inhibits
      the ATPase activity of Orc1, and ablates the ATP-dependent interaction of ORC
      with DNA. Here we present single particle electron microscopy (EM) studies of ORC
      bound to nucleotide in both the dephosphorylated and hyper-phosphorylated states.
      3D image reconstructions show that nucleotide binding gives rise to an analogous
      conformation independent of phosphorylation state. At the intermediate resolution
      achieved in our studies, ATP promotes changes along the toroidal core of the
      complex with negligible differences contributed by phosphorylation. Thus,
      hyperphosphorylation of DmORC does not induce meso-scale rearrangement of the ORC
      structure. To better understand ORC's role in origin remodeling, we performed
      atomic force microscopy (AFM) studies that show the contour length of a 688bp
      linear DNA fragment shortens by the equivalent of approximately 130bp upon ORC
      binding. This data, coupled with previous studies that showed a linking number
      change in circular DNA upon ORC binding, suggests that ORC may wrap the DNA in a
      manner akin to DnaA. Based on existing data and our structures, we propose a
      subunit arrangement for the AAA+ and winged helix domains, and in addition,
      speculate on a path of the 133bp of DNA around the ORC complex.

PMID- 18824235
TI  - Unmethylated CpG motifs mimicking bacterial DNA triggers the local and systemic
      innate immune parameters and expression of immune-relevant genes in gilthead
      seabream.
AB  - Unmethylated CpG motifs present in bacterial DNA are recognized by leucocyte
      receptors triggering an immune response. We have evaluated herein the
      immunomodulatory actions of a CpG motif in an important commercial fish, the
      gilthead seabream. Thus, 1, 3 and 7days after intraperitoneal injection of the
      CpG motif the seabream immune parameters and gene expression profile were
      evaluated. Firstly, humoral innate immune responses were unaffected by CpG ODN
      1668. On the other hand, ODN injection significantly enhanced the number of
      peritoneal leucocytes (PELs) 1day after injection and increased the main innate
      immune parameters of PELs and HKLs (head-kidney leucocytes). Thus, injection of
      ODN 1668 significantly increased respiratory burst, peroxidase, cytotoxic and
      phagocytic activities, with variations in increment and time. The cytotoxic
      activity of HKLs was the most increased (up to 4.2-fold). Moreover, the
      expression profile of immune-relevant genes in head-kidney was affected, with
      substantial up-regulation of TLR9, IL-1beta, Mx, TGFbeta and Gal8 gene
      expression. These results demonstrate that unmethylated CpG motifs prime the fish
      immune response with promising applications for aquaculture.

PMID- 18824236
TI  - Event-related functional MRI investigation of vocal pitch variation.
AB  - Voice production involves precise, coordinated movements of the intrinsic and
      extrinsic laryngeal musculature. A component of normal voice production is the
      modification of pitch. The underlying neural networks associated with these
      complex processes remains poorly characterized. However, several investigators
      are currently utilizing neuroimaging techniques to more clearly delineate these
      networks associated with phonation. The current study sought to identify the
      central cortical mechanism(s) associated with pitch variation during voice
      production using event-related functional MRI (fMRI). A single-trial design was
      employed consisting of three voice production tasks (low, comfortable, and high
      pitch) to contrast brain activity during the generation of varying frequencies.
      For whole brain analysis, volumes of activation within regions activated during
      each task were measured. Bilateral activations were shown in the cerebellum,
      superior temporal gyrus, insula, precentral gyrus, postcentral gyrus, inferior
      parietal lobe, and post-cingulate gyrus. In the left hemisphere, activations in
      the medial and middle frontal gyri were also observed. Regions active during high
      pitch production when compared to comfortable pitch were evident in the bilateral
      cerebellum, left inferior frontal gyrus, left cingulate gyrus, and left posterior
      cingulate. During low pitch generation, activations were present in the inferior
      frontal gyrus, insula, putamen, and cingulate gyrus in the left hemisphere. The
      inferior frontal gyrus in the right hemisphere produced greater activity than the
      area of the left hemisphere during high and low pitch generation. These results
      suggest that a single-trial design is sensitive enough to begin to delineate a
      widespread network of activations in both hemispheres associated with vocal pitch
      variation.

PMID- 18824237
TI  - Clarifying the systematics of an enigmatic avian lineage: what is a bombycillid?

PMID- 18824238
TI  - Inhibition of matrix metalloproteinase activity disrupts reconsolidation but not
      consolidation of a fear memory.
AB  - The reconsolidation hypothesis posits that memories that have been reactivated
      can be either enhanced or disrupted by pharmacological manipulation. Synaptic
      plasticity is presumed to underlie the reconsolidation process. Matrix
      metalloproteinases are proteins that regulate the extracellular matrix involved
      in plasticity events, and these proteins have recently been shown to influence
      learning and memory. However, all studies on the role of matrix
      metalloproteinases in learning and memory have employed tasks that rely on
      contextual cues. The goal of this study was to determine the extent to which FN
      439 would disrupt the consolidation and/or reconsolidation of a fear memory
      associated with a conditioned stimulus that signaled tone-shock pairings and that
      was independent of contextual cues. Male Sprague-Dawley rats were given infusions
      of FN-439 (35 microg intracerebroventricular) 30 min prior to conditioning (tone
      shock paired association) or 30 min prior to a single reactivation session given
      24h after conditioning. Administration of FN-439 did not disrupt consolidation of
      the freezing response when the tone (conditioned stimulus) was presented. In
      contrast, FN-439 infusion disrupted reconsolidation of the fear memory in a
      reactivation-dependent manner. The reduced freezing behavior was not due to a
      decrease in general anxiety levels, since FN-439 had no effect on the percent of
      open-arm time or open-arm entries in an elevated-plus maze task. Thus, we
      demonstrated for the first time that matrix metalloproteinase inhibition in the
      brain is capable of disrupting the reconsolidation of a tone-shock association
      memory that does not depend on contextual cues. The finding that a fear response
      to a previously paired conditioned stimulus can be disrupted by treatment with an
      MMP inhibitor during a single reactivation session suggests that this class of
      compounds may have therapeutic potential for posttraumatic stress disorder and/or
      simple phobias.

PMID- 18824239
TI  - Overexpression of a Trichoderma HSP70 gene increases fungal resistance to heat
      and other abiotic stresses.
AB  - All organisms share similar mechanisms in the heat shock response, such as
      synthesis of conserved heat shock proteins. Here, we report on the cloning,
      characterization and functional analysis of a Trichoderma harzianum T34 hsp70
      gene. The expression of this gene was evaluated in cultures grown in abiotic
      stress conditions. An increased level of expression was detected when the fungus
      was grown at 37 or 41 degrees C, as well as in the presence of oxidative or
      osmotic agents. The overexpression of hsp70 in T. harzianum T34 gave rise to
      transformants with higher quantities of biomass obtained after heat shock
      treatment. In addition, these transformants showed an enhanced tolerance to
      oxidative, osmotic and salt stresses when conidia were previously treated at 45
      degrees C for 2h.

PMID- 18824240
TI  - Multilocus genotyping and molecular phylogenetics resolve a novel head blight
      pathogen within the Fusarium graminearum species complex from Ethiopia.
AB  - A survey of Fusarium head blight (FHB)-contaminated wheat in Ethiopia recovered
      31 isolates resembling members of the Fusarium graminearum species complex.
      Results of a multilocus genotyping (MLGT) assay for FHB species and trichothecene
      chemotype determination suggested that 22 of these isolates might represent a new
      species within the Fg complex. Phylogenetic analyses of multilocus DNA sequence
      data resolved the 22 Ethiopian isolates as a novel, phylogenetically distinct
      species. The new species also appears to be novel in that MLGT probe data and
      sequence analysis of both ends of the TRI-cluster identified 15ADON and NIV
      recombination blocks, documenting inter-chemotype recombination involving the
      chemotype-determining genes near the ends of the TRI-cluster. Results of
      pathogenicity experiments and analyses of trichothecene mycotoxins demonstrated
      that this novel Fg complex species could induce FHB on wheat and elaborate 15ADON
      in planta. Herein the FHB pathogen from Ethiopia is formally described as a novel
      species.

PMID- 18824241
TI  - The CYPome (Cytochrome P450 complement) of Aspergillus nidulans.
AB  - The cytochromes P450 (CYPs) are found in all biological kingdoms and genome
      sequencing projects continue to reveal an ever increasing number. The principle
      aim of this paper is to identify the complete CYPome of Aspergillus nidulans from
      the genome sequence version AN.3 deposited at the Broad institute, assign the
      appropriate CYP nomenclature and define function where possible. The completed
      analysis revealed a total of 111 CYP genes, 3 of which were previously unknown
      and 8 pseudogenes, representing 89CYP families, 21 of which are unique. We have
      identified 28 potential gene clusters associated with one or more CYP genes and
      discussed those with putative PKS and NRPS associated function. The chromosomal
      location of the genes, predicted cellular location of the proteins and possible
      function(s) are discussed.

PMID- 18824242
TI  - Molecular characterization of iron binding proteins, transferrin and ferritin
      heavy chain subunit, from the bumblebee Bombus ignitus.
AB  - Transferrin and ferritin are iron-binding proteins involved in transport and
      storage of iron as part of iron metabolism. Here, we describe the cDNA cloning
      and characterization of transferrin (Bi-Tf) and the ferritin heavy chain subunit
      (Bi-FerHCH), from the bumblebee Bombus ignitus. Bi-Tf cDNA spans 2340 bp and
      encodes a protein of 706 amino acids and Bi-FerHCH cDNA spans 1393 bp and encodes
      a protein of 217 amino acids. Comparative analysis revealed that Bi-Tf appears to
      have residues comprising iron-binding sites in the N-terminal lobe, and Bi-FerHCH
      contains a 5'UTR iron-responsive element and seven conserved amino acid residues
      associated with a ferroxidase center. The Bi-Tf and Bi-FerHCH cDNAs were
      expressed as 79 kDa and 27 kDa polypeptides, respectively, in baculovirus
      infected insect Sf9 cells. Northern blot analysis revealed that Bi-Tf exhibits
      fat body-specific expression and Bi-FerHCH shows ubiquitous expression. The
      expression profiles of the Bi-Tf and Bi-FerHCH in the fat body of B. ignitus
      worker bees revealed that Bi-Tf and Bi-FerHCH are differentially induced in a
      time-dependent manner in a single insect by wounding, bacterial challenge, and
      iron overload.

PMID- 18824243
TI  - Elie Metchnikoff's and Paul Ehrlich's impact on infection biology.
AB  - The 100th anniversary of the Nobel Prize for Medicine to Paul Ehrlich and Elie
      Metchnikoff gives us a good opportunity to reflect on their research about
      infectious diseases. Elie Metchnikoff was not only the first to describe
      phagocytosis of invading pathogens by specialized blood cells - macrophages and
      neutrophils - he also was interested in the impact of normal flora on well-being
      and in pre- and probiotic diet and their influence on the normal flora. Paul
      Ehrlich not only developed the concept of the side-chain theory of antibody
      formation but also discovered the first chemotherapeutic agent against microbial
      pathogens through a combination of chemical modification of a lead substance and
      experimental animal screening on a broad-scale. Hence, they are not only the
      founders of immunology but also were the first to envisage infection biology as
      the result of an interplay between host and pathogen.

PMID- 18824244
TI  - Physiological relevance of GPCR oligomerization and its impact on drug discovery.
AB  - The potentially large functional and physiological diversity of G-protein coupled
      receptor (GPCR) dimers has generated a great deal of excitement about the
      opportunity that dimerization provides for enabling novel drug discovery. The
      discovery of physiologically relevant GPCR dimers suggests that new drug targets
      for diseases such as schizophrenia and pre-eclampsia can be developed by
      targeting dimers. Most of the previous work on GPCR dimers made use of the
      overexpression of differentially tagged GPCRs in heterologous cell systems.
      Current emphasis on the development of physiologically relevant cell systems that
      endogenously express the appropriate combination of GPCR dimers and accessory
      proteins is leading to dramatic increases in our understanding of GPCR dimers.
      These and other new tools such as GPCR-specific antibodies will be required to
      develop GPCR dimer specific drugs. Given that ligands are available for only a
      small percentage of the large number of potentially druggable GPCRs, the use of
      GPCR dimers might provide the necessary targets to increase the breadth and depth
      of receptors available for therapeutic interventions.

PMID- 18824245
TI  - New therapeutics for the prevention and reduction of scarring.
AB  - Published literature shows that both physicians and patients are highly concerned
      about scarring and value even small improvements in scar appearance. Both severe
      and relatively minor scars can have a significant psychological impact on
      patients, irrespective of whether or not they are hidden by clothing. There is no
      universal standard of care for scarring and, currently, no marketed
      pharmaceuticals for the prophylactic reduction of scarring. Novel approaches are
      under development, with the furthest progressed being avotermin (Juvista;
      transforming growth factor beta 3). The scar-improvement efficacy of this agent,
      administered at the time of surgery, has been demonstrated in robust, well
      controlled, randomized human studies. Avotermin and other agents in development
      represent a new class of prophylactic medicines promoting the regeneration of
      normal skin and improving scar appearance.

PMID- 18824246
TI  - Distinct patterns of electrical stimulation of the basolateral amygdala influence
      pentylenetetrazole seizure outcome.
AB  - Our working hypothesis is that constant interpulse interval (IPI) electrical
      stimulation would resonate with endogenous epileptogenic reverberating circuits,
      inducing seizures, whereas a random interinterval electrical stimulation protocol
      would promote desynchronization of such neural networks, producing an
      anticonvulsant effect. Male Wistar rats were stereotaxically implanted with a
      bipolar electrical stimulation electrode in the amygdala. Pentylenetetrazole
      (10mg/ml/min) was continuously infused through an intravenous catheter to induce
      seizures while four different patterns of temporally coded electrical stimulation
      were applied: periodic stimulation (PS), pseudo-randomized IPI stimulation (LH),
      restrictively randomized IPI stimulation (IH), and bursts of 20-ms IPIs (burst).
      PS decreased the pentylenetetrazole threshold to forelimb clonus, whereas IH
      increased the threshold to forelimb clonus and to generalized tonic-clonic
      seizures. We hypothesize that PS facilitates forelimb clonus by reverberating
      with epileptogenic circuits in the limbic system, whereas IH delays forelimb
      clonus and generalized tonic-clonic seizures by desynchronizing the epileptic
      neural networks in the forebrain-midbrain-hindbrain circuits.

PMID- 18824247
TI  - Responsiveness of the interrenal tissue of Jundia (Rhamdia quelen) to an in vivo
      ACTH test following acute exposure to sublethal concentrations of agrichemicals.
AB  - As in many aquatic environments, pollution is a widespread problem in Southern
      Brazil. In our previous work, we demonstrated that sublethal contamination with
      some agrichemicals impairs the capacity of fishes to elevate cortisol levels in
      response to an additional acute stressor. In earlier experiments, the
      experimental design did not allow us to conclude where this effect occurs. In the
      present work, we used the adrenocorticotropic hormone (ACTH) challenge test to
      help us identify if the impairment occur in the interrenal tissue. For this
      purpose, five experiments were conducted, each with one specific agrichemical
      (methyl-parathion, atrazine+simazine, atrazine, tebuconazole, and glyphosate) in
      sublethal concentrations of 16.6% of the LC(50-96h), as previously determined.
      Fish were subjected to the ACTH challenge test protocol as follows: group 1, were
      non-injected and maintained as the specific control group; group 2 received an
      injection of the vehicle alone (the saline group); and group 3 receive an
      injection of ACTH. One hour later, blood samples were taken from the caudal
      plexus, using sterile syringes. In all specific control groups, the injection of
      ACTH induced a strong rise in plasma cortisol, compared with the fish injected
      only with the vehicle and the non-injected group. Fish exposed to methyl
      parathion and tebuconazole did not elevate cortisol in response to the ACTH
      injection, with values significantly lower than the control fish. Fish exposed to
      sublethal concentrations of atrazine+simazine, atrazine, and glyphosate showed a
      rise in plasma cortisol very similar to the control fish. We conclude that the
      ACTH challenge test revealed that R. quelen exposed to sublethal concentrations
      of tebuconazole and methyl-parathion had a reduced ability to elevate plasma
      cortisol in response to an intraperitoneal (i.p.) injection of exogenous ACTH,
      indicating that the interrenal tissue is the site of the impairment within the
      HPI axis. These ACTH challenge tests also revealed that the impairment of the
      cortisol response verified in fish exposed to atrazine+simazine and glyphosate,
      as shown in our previous work, seems to be related to steps of cortisol secretion
      in higher levels within the HPI axis.

PMID- 18824248
TI  - Structural group-based auditing of missing hierarchical relationships in UMLS.
AB  - The Metathesaurus of the UMLS was created by integrating various source
      terminologies. The inter-concept relationships were either integrated into the
      UMLS from the source terminologies or specially generated. Due to the extensive
      size and inherent complexity of the Metathesaurus, the accidental omission of
      some hierarchical relationships was inevitable. We present a recursive procedure
      which allows a human expert, with the support of an algorithm, to locate missing
      hierarchical relationships. The procedure starts with a group of concepts with
      exactly the same (correct) semantic type assignments. It then partitions the
      concepts, based on child-of hierarchical relationships, into smaller, singly
      rooted, hierarchically connected subgroups. The auditor only needs to focus on
      the subgroups with very few concepts and their concepts with semantic type
      reassignments. The procedure was evaluated by comparing it with a comprehensive
      manual audit and it exhibits a perfect error recall.

PMID- 18824249
TI  - Orally administered apple procyanidins protect against experimental inflammatory
      bowel disease in mice.
AB  - Apple procyanidins (ACT) is a natural biologically active compound extracted from
      apple. Our recent studies have shown that ACT ameliorates the symptoms of atopic
      dermatitis and inhibits food-allergen-induced oral sensitization. The aim of this
      study was to investigate the potential protective effect and mechanism of action
      of ACT in a murine model of inflammatory bowel disease. We investigated the
      preventive effects of ACT in experimental models of colitis induced by dextran
      sulfate sodium (DSS) or oxazolone. Oral administration of ACT before DSS
      treatment attenuated the DSS-induced mortality rate and decreased body weight
      loss. ACT also prevented the body weight loss associated with oxazolone-induced
      colitis. Next we examined the effect of ACT on intraepithelial lymphocytes (IEL),
      which is a major T cell population in the intestine. Oral administration of ACT
      increased the proportions of TCRgammadelta and TCRalphabeta-CD8alphaalpha T cells
      in IEL and suppressed interferon gamma synthesis in stimulated IEL. In addition,
      ACT inhibited phorbol 12-myristate 13-acetate-induced secretion of interleukin 8
      (IL-8) in intestinal epithelial cells. The combined anti-inflammatory and
      immunomodulatory effects of ACT on intestinal epithelial cells and IEL suggest
      that it may be an effective oral preventive agent for inflammatory bowel
      diseases.

PMID- 18824250
TI  - Fructose-1,6-diphosphate attenuates acute lung injury induced by
      lipopolysaccharide in mice.
AB  - Fructose-1,6-diphosphate (FDP), a high-energy glycolytic pathway intermediate, is
      reported to have a salutary effect in endotoxic shock and sepsis, but its
      underlying mechanism of action in inflammation is incompletely understood. In
      this study, our aim was to examine the function of FDP on acute lung injury (ALI)
      induced by lipopolysaccharide (LPS). We found that in vitro pretreatment with FDP
      remarkably repressed the production of TNF-alpha and IL-6 in murine alveolar
      macrophages MH-S exposed to LPS. In the mouse model of LPS-induced inflammatory
      lung injury, intravenous precondition of a single 400 mg/kg dose of FDP resulted
      in a significant reduction in LPS-mediated extravasation of Evans blue dye
      albumin, bronchoalveolar lavage leucocyte content, and lung tissue
      myeloperoxidase activity (reflecting phagocyte infiltration). Furthermore,
      histopathologic examination indicated that alveolitis with inflammatory cells
      infiltration and alveolar hemorrhage in the alveolar space was less severe in the
      FDP-treated mice than in the mice treated by LPS alone at 24 h. Additionally,
      pretreatment with FDP markedly decreased the transcription of TNF-alpha, IL-6 and
      inducible NO synthase (iNOS), and suppressed the nuclear translocation of NF
      kappaB in lung tissues in response to LPS challenge. These results thus suggested
      that FDP plays an anti-inflammatory role in LPS-mediated acute lung injury,
      possibly through abrogation of NF-kappaB activation.

PMID- 18824251
TI  - Double-strand break DNA repair genotype predictive of later mortality and cancer
      incidence in a cohort of non-smokers.
AB  - We followed-up for mortality and cancer incidence 1088 healthy non-smokers from a
      population-based study, who were characterized for 22 variants in 16 genes
      involved in DNA repair pathways. Follow-up was 100% complete. The association
      between polymorphism and mortality or cancer incidence was analyzed using Cox
      Proportional Hazard regression models. Ninety-five subjects had died in a median
      follow-up time of 78 months (inter-quartile range 59-93 months). None of the
      genotypes was clearly associated with total mortality, except variants for two
      Double-Strand Break DNA repair genes, XRCC3 18067 C>T (rs#861539) and XRCC2 31479
      G>A (rs#3218536). Adjusted hazard ratios were 2.25 (1.32-3.83) for the XRCC3 C/T
      genotype and 2.04 (1.00-4.13) for the T/T genotype (reference C/C), and 2.12
      (1.14-3.97) for the XRCC2 G/A genotype (reference G/G). For total cancer
      mortality, the adjusted hazard ratios were 3.29 (1.23-7.82) for XRCC3 C/T, 2.84
      (0.81-9.90) for XRCC3 T/T and 3.17 (1.21-8.30) for XRCC2 G/A. With combinations
      of three or more adverse alleles, the adjusted hazard ratio for all cause
      mortality was 17.29 (95% C.I. 8.13-36.74), and for all incident cancers the HR
      was 5.28 (95% C.I. 2.17-12.85). Observations from this prospective study suggest
      that polymorphisms of genes involved in the repair of DNA double-strand breaks
      significantly influence the risk of cancer and non-cancer disease, and can
      influence mortality.

PMID- 18824252
TI  - Ecorisk evaluation and treatability potential of soils contaminated with
      petroleum hydrocarbon-based fuels.
AB  - We used a series of toxicity tests to monitor oil degradation in the Kuwaiti oil
      lakes. Three soils from different locations with a history of hydrocarbon
      contamination were treated in bench-scale microcosms with controlled nutrient
      amendments, moisture content, and temperature that had promoted mineralization of
      total hydrocarbon and oil and grease in a preliminary study. Two hundred days of
      bioremediation treatment lowered hydrocarbon concentration to below 2 and 5 mg g(
      1) for soils A and B, respectively, while in soil C hydrocarbon concentration
      remained at 12 mg g(-1). Although 85% of the total petroleum hydrocarbons (TPHs)
      in soil A were reduced 50d after treatment, results of the seed germination and
      Microtox tests suggested an initial increase in toxicity, indicating that toxic
      intermediary metabolites may have formed during biodegradation. Also, the
      significant decrease of TPHs and corresponding high toxicity levels were noted in
      soil B 200d after bioremediation. Clearly, toxicity values, and not just
      hydrocarbon concentration, are a key factor in assessing the effectiveness of
      bioremediation techniques. Field chemistry data showed a significant reduction in
      hydrocarbon levels after the biological treatment. We concluded that the toxicity
      assessment of the contaminated soil with a battery of toxicity bioassays could
      provide meaningful information regarding a characterization procedure in
      ecological risk assessment.

PMID- 18824253
TI  - Enamel-dentine junction (EDJ) morphology distinguishes the lower molars of
      Australopithecus africanus and Paranthropus robustus.
AB  - Tooth crown morphology plays a central role in hominin systematics, but the
      removal of the original outer enamel surface by dental attrition often eliminates
      from consideration the type of detailed crown morphology that has been shown to
      discriminate among hominin taxa. This reduces the size of samples available for
      study. The enamel-dentine junction (EDJ) is the developmental precursor and
      primary contributor to the morphology of the unworn outer enamel surface, and its
      morphology is only affected after considerable attrition. In this paper, we
      explore whether the form of the EDJ can be used to distinguish between the
      mandibular molars of two southern African fossil hominins: Paranthropus (or
      Australopithecus) robustus and Australopithecus africanus. After micro-computed
      tomographic scanning the molar sample, we made high-resolution images of the EDJ
      and used geometric morphometrics to compare EDJ shape differences between
      species, in addition to documenting metameric variation along the molar row
      within each species. Landmarks were collected along the marginal ridge that runs
      between adjacent dentine horns and around the circumference of the cervix. Our
      results suggest that the morphology of the EDJ can distinguish lower molars of
      these southern African hominins, and it can discriminate first, second, and third
      molars within each taxon. These results confirm previous findings that the EDJ
      preserves taxonomically valuable shape information in worn teeth. Mean
      differences in EDJ shape, in particular dentine horn height, crown height, and
      cervix shape, are more marked between adjacent molars within each taxon than for
      the same molar between the two taxa.

PMID- 18824254
TI  - Indications of habitat association of Australopithecus robustus in the Bloubank
      Valley, South Africa.
AB  - Establishing the habitat preferences of early hominin taxa is a necessary, though
      difficult, requirement for understanding the interaction between environmental
      change and hominin evolution. The environments typically associated with
      Australopithecus robustus have been reconstructed as predominantly open
      grasslands situated within a habitat mosaic that included a more wooded component
      with a nearby perennial water source. Most studies have concluded that the open
      grassland component represents the habitat preference of the hominins. In this
      study we investigate indicators of habitat association of A. robustus that are
      preserved in the animal paleocommunities represented in a series of fossil cave
      infills in the Bloubank Valley of South Africa, including Swartkrans,
      Sterkfontein, Kromdraai, and Coopers. Testing for conditions of isotaphonomy
      reveals a potential bias relating to depositional matrix and perhaps accumulating
      agent, though such a bias has not unduly influenced the taxonomic composition the
      assemblages. Correspondence analysis of census data from modern African nature
      reserves demonstrates that carnivore predation patterns are indicative of animal
      communities, which in turn are representative of habitats. As a result, modern
      census data are used to document patterns of habitat preference of large
      herbivores, thus allowing assignment of fossil taxa to a series of broadly
      defined habitat categories. Correspondence analysis of fossil assemblages reveals
      that the abundance profile of A. robustus is most similar to that of woodland
      adapted taxa. In addition, fluctuations in the relative abundance of taxa
      assigned to the broad habitat categories reveal a significant negative
      correlation between A. robustus and open grassland-adapted taxa, indicating that
      the more grassland-adapted taxa there are in a given assemblage, the fewer
      hominins there tend to be. Thus, it appears that the open grasslands that
      comprise the majority of the paleoenvironments associated with A. robustus do not
      necessarily indicate the habitat preference of the hominins. Rather, it would
      appear that in addition to being dietary generalists, A. robustus were also
      likely to have been habitat generalists.

PMID- 18824255
TI  - Adverse pregnancy outcomes in a population exposed to the emissions of a
      municipal waste incinerator.
AB  - Some contaminants emitted by municipal waste incinerators are believed to
      adversely affect reproductive health in the exposed populations; yet only limited
      and conflicting epidemiologic evidence on this issue has been provided so far. In
      this study we analyzed rates of spontaneous abortion and prevalence at birth of
      congenital anomalies in women residing or working near the municipal solid waste
      incinerator of Modena, northern Italy, during the 2003--2006 period and who
      experienced higher levels of exposure to polychlorinated dibenzo-p-dioxins and
      dibenzofurans, compared to the remaining municipal population. In women residing
      in two areas close to the incinerator plant with increasing exposure to dioxins,
      we did not detect an excess risk of miscarriage (relative risk [RR] 1.00, 95%
      confidence interval [CI] 0.65-1.48) and of birth defects (RR 0.64, 95% CI 0.20
      1.55), nor did any indication of dose-response relation emerge. Among female
      workers employed in the factories located in the exposed areas, we did not
      observe a higher risk of spontaneous abortion (RR 1.04, 95% CI 0.38-2.30);
      however, an increase in prevalence of birth defects was noted (RR 2.26), although
      this risk estimate was statistically very unstable (95% CI 0.57-6.14). Overall,
      the study results provide little evidence of an excess risk of adverse pregnancy
      outcomes in women exposed to emissions from a modern municipal solid waste
      incinerator.

PMID- 18824256
TI  - VTE in patients with cancer--diagnosis, prevention, and treatment.
AB  - Management of venous thromboembolism (VTE) in patients with cancer is
      challenging. In addition, cancer-associated thrombosis (CAT) is becoming an
      increasingly prevalent condition because of the aging population, the
      aggressiveness of anticancer therapies, and the improved survival of patients
      with cancer. Diagnosis of CAT can be difficult because many cancer patients
      without acute thrombosis often have with signs and symptoms that mimic those of
      deep vein thrombosis or pulmonary embolism, while others are found to have
      clinically silent VTE incidentally on routine staging investigations for their
      cancer. Prevention of CAT is important for reducing the burden of disease but it
      has received very little attention from clinicians and researchers. Treatment of
      CAT is also challenging because oncology patients have a high risk of recurrent
      thrombosis and major bleeding even while receiving anticoagulant therapy. This
      review will focus on the current standards of practice for the diagnosis,
      prevention and treatment of VTE in patients with cancer.

PMID- 18824257
TI  - Expression of alpha-gustducin in the circumvallate papillae of taste buds of
      diabetic rats.
AB  - Taste impairment is a complication of Diabetes mellitus and some studies have
      shown this taste disorder in diabetes. Diabetes can decrease the ability of
      individuals to detect and recognize sweet, salty and bitter tastes. alpha
      Gustducin is a transducin-like G-protein selectively expressed in 20 - 30% of
      taste receptor cells, which has been shown to be involved in bitter, sweet and
      umami taste responses. The present study was performed to explore the protein and
      mRNA expression of alpha-gustducin in the taste buds of diabetic and control rat
      circumvallate papillae. Our results showed that the positive expression of alpha
      gustducin in diabetic rat taste bud cells is higher than that in normal controls
      as shown by both immunohistochemistry and RT-PCR. There may be some variant of
      bitter, sweet or umami taste transduction during diabetes and that taste
      transduction variant may be one cause of diabetic taste impairment.

PMID- 18824258
TI  - A specific drug targeting system based on polyhydroxyalkanoate granule binding
      protein PhaP fused with targeted cell ligands.
AB  - Polyhydroxyalkanoates (PHA) is a family of intracellular biopolyesters produced
      by many bacteria. PHA granule binding protein PhaP is able to bind to hydrophobic
      polymers via strong hydrophobic interaction. A receptor-mediated drug delivery
      system was developed in this study based on PhaP. The system consists of PHA
      nanoparticles, PhaP and polypeptide or protein ligands fused to PhaP. The PHA
      nanoparticles were used to package mostly hydrophobic drugs; PhaP fused with
      ligands produced by over-expression of their corresponding genes in Pichia
      pastoris, or E. coli was able to attach to hydrophobic PHA nanoparticle. At the
      end, the ligands were able to pull the PhaP-PHA nanoparticles to the targeted
      cells with receptors recognized by the ligands. It was found in this study that
      the receptor-mediated drug specific delivery system ligand-PhaP-PHA nanoparticles
      were taken up by macrophages, hepatocellular carcinoma cell BEL7402 in vitro and
      liver, hepatocellular carcinoma cells in vivo, respectively, when the ligands
      were mannosylated human alpha1-acid glycoprotein (hAGP) and human epidermal
      growth factor (hEGF), respectively, which were able to bind to receptors of
      macrophages or hepatocellular carcinoma cells. The nanoparticle system was
      clearly visible in the targeted cells and organs (liver or tumor) under
      fluorescence microscopy when rhodamine B isothiocyanate (RBITC) was used as a
      delivery model drug due to the specific targeting effect created by specific
      ligand and receptor binding. The delivery system of hEGF-PhaP-nanoparticles
      carrying RBITC was found to be endocytosed by the tumor cells in tumorous model
      mice. Thus, the ligand-PhaP-PHA specific drug delivery system was proven
      effective both in vitro and in vivo.

PMID- 18824259
TI  - Systemic trafficking of macrophages induced by bone cement particles in nude
      mice.
AB  - Macrophages play an important role in the biological response to wear particles,
      which can result in periprosthetic osteolysis and implant loosening. In this
      study, we demonstrate that polymer particles induce systemic trafficking of
      macrophages by non-invasive in vivo imaging and immunohistochemistry. The distal
      femora of nude mice were injected with 10% (w/v) Simplex bone cement (BC)
      suspensions or saline (PBS). Reporter RAW264.7 macrophages which stably expressed
      the bioluminescent reporter gene fluc, and the fluorescence reporter gene gfp,
      were injected intravenously. Bioluminescence imaging was performed immediately
      and periodically at 2-day intervals until day 14. Compared to the non-operated
      contralateral femora, the bioluminescent signal of femora injected with BC
      suspension increased 4.7+/-1.6 and 7.8+/-2.9-fold at day 6 and 8, respectively.
      The same values for PBS group were 1.2+/-0.2 and 1.4+/-0.5, respectively. The
      increase of bioluminescence of the BC group was significantly greater than the
      PBS group at day 8 (p<0.05) and day 6 (p<0.1). Histological study confirmed the
      presence of reporter macrophages within the medullary canal of mice that received
      cement particles. Modulation of the signaling mechanisms that regulate systemic
      macrophage trafficking may provide a new strategy for mitigating the chronic
      inflammatory response and osteolysis associated with wear debris.

PMID- 18824260
TI  - Biodegradable poly(polyol sebacate) polymers.
AB  - We have developed a family of synthetic biodegradable polymers that are composed
      of structural units endogenous to the human metabolism, designated poly(polyol
      sebacate) (PPS) polymers. Material properties of PPS polymers can be tuned by
      altering the polyol monomer and reacting stiochiometric ratio of sebacic acid.
      These thermoset networks exhibited tensile Young's moduli ranging from 0.37+/
      0.08 to 378+/-33 MPa with maximum elongations at break from 10.90+/-1.37% to
      205.16+/-55.76%, and glass transition temperatures ranging from approximately 7
      46 degrees C. In vitro degradation under physiological conditions was slower than
      in vivo degradation rates observed for some PPS polymers. PPS polymers
      demonstrated similar in vitro and in vivo biocompatibility compared to poly(L
      lactic-co-glycolic acid) (PLGA).

PMID- 18824261
TI  - Targeted suppression of MCT-1 attenuates the malignant phenotype through a
      translational mechanism.
AB  - The MCT-1 oncogene, highly expressed in a subset of non-Hodgkin's lymphomas
      interacts with the cap complex through its PUA domain. MCT-1 recruits DENR, a
      SUI1 motif containing protein that promotes translation initiation of cancer
      related mRNAs. We reasoned that a PUA-domain mutant protein would repress MCT-1
      function and attenuate the malignant phenotype. Human lymphoma cell lines
      expressing the PUA-domain mutant protein demonstrated reduced anchorage
      independent growth and increased susceptibility to apoptosis. Significantly, we
      identified an altered translational profile in cells expressing the mutant
      protein. These data further buttress the role of the MCT-1 in lymphomagenesis and
      support the development of novel therapeutic strategies targeting MCT-1.

PMID- 18824262
TI  - The fragmented testis method: development and its advantages of a new
      quantitative evaluation technique for detection of testis-ova in male fish.
AB  - A new quantitative evaluation technique, termed the fragmented testis method, has
      been developed for the detection of testis-ova in genotypic male fish using the
      medaka (Oryzias latipes). The routine traditional histological method for
      detection of testis-ova in male fish exposed to estrogens or suspected endocrine
      disrupting chemicals has several disadvantages, including possible oversight of
      testis-ova due to limited sampling of selected tissue sections. The method we
      have developed here allows for the accurate determination of the developmental
      stages and the number and the size of testis-ova in a whole testis. Each testis
      was removed from the fish specimen, fixed with 10% buffered formalin solution,
      and then divided into small fragments on a glass slide with a dissecting needle
      or scalpel and aciform forceps in glycerin solution containing a small amount of
      methylene blue or toluidine blue. If present, all developing testis-ova of
      various sizes in fragmented testicular tissues were clearly stained and were
      observable under a dissecting microscope. Testis-ova occurred in controls were
      ascertained, while spermatozoa were also distinguishable using this method. This
      proved to be a convenient and cost-effective method for quantitatively evaluating
      testis-ova appearance in fish, and it may help to clarify the mechanism of testis
      ova formation and the biological significance of testis-ova in future studies of
      endocrine disruption.

PMID- 18824263
TI  - Phthalate exposure among pregnant women in Jerusalem, Israel: results of a pilot
      study.
AB  - BACKGROUND: Phthalates can disrupt endocrine function and induce reproductive and
      developmental toxicity in laboratory animals. Few studies have evaluated exposure
      to phthalates in pregnant women, despite the potential sensitivity of the
      developing fetus to adverse effects of phthalates. METHODS: We measured urinary
      concentrations of 11 phthalate metabolites in 19 pregnant women, recruited in
      Jerusalem, Israel in 2006, and collected questionnaire data on demographic
      factors and consumer habits from these women. We compared geometric mean
      concentrations in subgroups and used the Mann-Whitney U-test for independent
      samples to determine significant differences between groups. RESULTS: Nine
      metabolites were detected in at least 95% of the samples: mono(2-ethyl-5
      carboxypentyl) phthalate, mono(2-ethyl-5-hydroxyhexyl) phthalate, mono(2-ethyl-5
      oxohexyl) phthalate, mono(3-carboxypropyl) phthalate, mono(n-butyl) phthalate,
      monobenzyl phthalate (MBzP), monoethyl phthalate (MEP), mono(2-ethylhexyl)
      phthalate and monoisobutyl phthalate. Phthalate metabolite concentrations in
      these pregnant women were remarkably similar to those in the general United
      States female population. MBzP geometric mean concentrations were higher in women
      living in buildings existing 40 years or more (P=0.04). In women who used four or
      more personal care products (perfume, deodorant, lipstick, nail polish, or
      hand/face cream) in the 48 h prior to providing the urine sample, geometric mean
      MEP concentrations were more than 4 times higher than concentrations in women
      using only two or three of the aforementioned products (P=0.07). CONCLUSIONS:
      Pregnant women in Jerusalem are exposed to a wide range of phthalates. Building
      materials used in old constructions may be a source of exposure to benzylbutyl
      phthalate, the parent compound of MBzP. Personal care products may be sources of
      exposure to diethyl phthalate, the parent compound of MEP.

PMID- 18824264
TI  - Murine ovarian cancer vascular leukocytes require arginase-1 activity for T cell
      suppression.
AB  - The predominant leukocyte population present in both human and murine peritoneal
      ovarian tumors is the Vascular Leukocyte (VLC). VLCs are recruited en masse to
      the ovarian tumor microenvironment whereupon they promote tumor progression.
      Importantly, the presence of VLCs is requisite for peritoneal ovarian cancer
      progression: selective elimination of VLCs inhibits tumor burden and ascites
      accumulation. Despite the critical importance of VLCs to ovarian tumors, their
      derivation and the mechanisms by which they facilitate tumor progression are not
      well understood. Here we demonstrate in vivo that the murine ID8 ovarian tumor
      model can usurp the host peritoneal macrophage pathway to elicit and recruit
      VLCs. Moreover, we demonstrate that VLCs express CD11b and Gr-1, a characteristic
      phenotype shared amongst heterogeneous populations of leukocytes referred to as
      myeloid-derived suppressor cells (MDSCs). In accord with their MDSC phenotype,
      both murine and human VLCs express arginase-1 (ARG1). Importantly, we demonstrate
      that the VLCs suppress both CD8(+) and CD4(+) T cells responses and that this
      immunosuppression is ARG1-dependent, since blockade of VLC ARG1 activity with nor
      NOHA reversed the immunosuppression. These data further characterize the tumor
      associated leukocytes in ovarian cancer and provide insights into the mechanisms
      by which they promote tumor growth.

PMID- 18824265
TI  - Reference genes for canine skin when using quantitative real-time PCR.
AB  - Quantitative real-time PCR (qPCR) facilitates the quantification of mRNA
      expression. Accurate qPCR analysis of gene expression requires the normalisation
      of data using a reference or housekeeping gene which is expressed at a similar
      level in all tissues tested. GAPDH is the most well known and most widely used
      reference gene but many papers have demonstrated that it is not stably expressed
      in different tissues. The aim of this study was to measure reference gene
      stability in canine skin using real-time qPCR. Skin samples from healthy control
      dogs (n=7) and dogs with atopic dermatitis (lesional skin n=7 and non-lesional
      skin n=7) were used to quantify seven reference genes (IMP, CG14980, S7, HIRA,
      GAPDH, RPL13A and SDHA) in canine whole skin. Three different statistical
      programs (Bestkeeper, GeNorm and Normfinder) were used to assess the stability of
      the reference genes. The results confirmed that GAPDH is not a stably expressed
      reference gene in canine skin; this finding may influence interpretation of
      previous qPCR studies on canine skin using this as a reference gene. RPL13A and
      CG14980 were found to be the most stably expressed genes in canine whole skin and
      would be more suitable as reference genes in future studies.

PMID- 18824266
TI  - Distinct fractional Abeta release patterns in human mononuclear phagocytes.
AB  - The presence of cells of the mononuclear phagocyte lineage surrounding neuritic
      and vascular beta-amyloid (Abeta) plaques is a hallmark of Alzheimer's disease
      (AD) neuropathology. The fractional Abeta peptide patterns released by human
      mononuclear phagocyte (MNP), lymphocyte and PBMC cultures were assessed by Abeta
      SDS-PAGE/immunoblot and compared with the Abeta patterns in neuronal
      supernatants, in cerebrospinal fluid (CSF), and plasma. MNP released substantial
      amounts of Abeta peptides and the Abeta pattern contrasted with that in neuronal
      supernatants, CSF and plasma by reduced Abeta(1-42) and increased proportions of
      N-truncated Abeta species. MNP derived from early AD patients released
      significantly more total Abeta peptides than age-matched controls. The proportion
      of Abeta(1-42) was not altered.

PMID- 18824267
TI  - What contributes to the sensitivity of microalgae to triclosan?
AB  - Differential sensitivities of microalgae to triclosan have been reported, which
      may have significant implications for environmental risk assessment of this
      widely used biocide. Therefore, the aim of this study was to derive a mechanistic
      understanding of varying microalgal sensitivity to this substance. The toxicity
      of triclosan was evaluated using microalgal systems varying in biological
      complexity, exposure time and systematic position (a synchronized culture of the
      chlorophyte Scenedesmus vacuolatus, a diatom Nitzschia palea cultivated in
      suspension as well as attached to surfaces and periphyton communities). The
      results revealed (1) differences in sensitivity of the selected microalgal
      systems of three orders of magnitude and (2) highest sensitivity of the
      chlorophyte to triclosan in the range of environmental concentrations. To
      investigate algal sensitivity to triclosan in more detail, bioavailability was
      considered by investigating suspended and attached living algae. Differences in
      the generation time (in comparison to test duration) of the species were
      addressed by evaluating and modeling concentration-time-effect relationships.
      However, varying sensitivities of the selected microalgal systems remained
      unexplained. Comparison of species-specific toxic responses to calculated effect
      concentrations, derived from quantitative relationships for narcosis and
      uncoupling mode-of-action, leads us to the conclusion that triclosan may address
      multiple target sites in different microalgal species.

PMID- 18824268
TI  - Heterogeneous impact of the "Seguro Popular" program on the utilization of
      obstetrical services in Mexico, 2001-2006: a multinomial probit model with a
      discrete endogenous variable.
AB  - OBJECTIVE: We evaluated the impact of Seguro Popular (SP), a program introduced
      in 2001 in Mexico primarily to finance health care for the poor. We focused on
      the effect of household enrollment in SP on pregnant women's access to
      obstetrical services, an important outcome measure of both maternal and infant
      health. DATA: We relied upon data from the cross-sectional 2006 National Health
      and Nutrition Survey (ENSANUT) in Mexico. We analyzed the responses of 3890 women
      who delivered babies during 2001-2006 and whose households lacked employer-based
      health care coverage. METHODS: We formulated a multinomial probit model that
      distinguished between three mutually exclusive sites for delivering a baby: a
      health unit specifically accredited by SP; a non-SP-accredited clinic run by the
      Department of Health (Secretaria de Salud, or SSA); and private obstetrical care.
      Our model accounted for the endogeneity of the household's binary decision to
      enroll in the SP program. RESULTS: Women in households that participated in the
      SP program had a much stronger preference for having a baby in a SP-sponsored
      unit rather than paying out of pocket for a private delivery. At the same time,
      participation in SP was associated with a stronger preference for delivering in
      the private sector rather than at a state-run SSA clinic. On balance, the Seguro
      Popular program reduced pregnant women's attendance at an SSA clinic much more
      than it reduced the probability of delivering a baby in the private sector. The
      quantitative impact of the SP program varied with the woman's education and
      health, as well as the assets and location (rural vs. urban) of the household.
      CONCLUSIONS: The SP program had a robust, significantly positive impact on access
      to obstetrical services. Our finding that women enrolled in SP switched from non
      SP state-run facilities, rather than from out-of-pocket private services, is
      important for public policy and requires further exploration.

PMID- 18824269
TI  - On-farm spread of Mycobacterium avium subsp. paratuberculosis in raw milk studied
      by IS900 and F57 competitive real time quantitative PCR and culture examination.
AB  - A rapid, cheap and sensitive detection method of Mycobacterium avium subsp.
      paratuberculosis (MAP) in raw milk was needed for routine usage. We developed two
      duplex real time qPCR systems specific for MAP detection. These real time qPCR
      assays amplify the multicopy element IS900 for qualitative analysis and the
      single copy element F57 for quantitative analysis. Both assays incorporate an
      internal amplification control amplified with the same primers as the targets and
      the same probes are used in both assays. The specificity of the assays was
      confirmed by the testing of 6 different MAP isolates, 12 isolates of other
      mycobacteria or bacterial species and 4 different mammalian DNAs. The sensitivity
      of the developed assays and isolation efficiency were demonstrated through the
      analysis of raw milk samples artificially contaminated with MAP cells and with
      plasmids containing cloned fragments of the targets (IS900 and F57). The
      developed assays for milk analysis were applied to samples from one farm with two
      faecal shedding cows. Three hundred and forty five individual milk samples were
      tested by real time qPCR assays and by cultivation. Hundred and eleven (32.5%)
      individual milk samples were positive by the real time qPCR, no milk sample was
      culture positive. The spread of MAP in individual, tank and bulk tank milk
      samples was also monitored.

PMID- 18824270
TI  - Cardiovascular autonomic neuropathy, autonomic symptoms and diabetic
      complications in 674 type 2 diabetes.
AB  - AIMS: To determine the relationships between cardiovascular autonomic neuropathy
      (CAN) and autonomic symptoms, clinical parameters and diabetic complications in
      type 2 diabetes (T2DM). METHODS: The results of autonomic symptoms, clinical
      parameters, diabetes complications and cardiovascular reflex (CVR) tests of 674
      T2DM were analyzed. RESULTS: Significant correlations were found between CAN risk
      and age (p=0.019), duration of diabetes (p=0.008), HbA1c (p<0.001), systolic
      blood pressure (p=0.006), nephropathy (p<0.001), retinopathy (p<0.001), and QTc
      interval (p<0.001), but not BMI and hyperlipidemia. Patients with retinopathy or
      proteinuria had increase risk of CAN, and proliferative diabetic retinopathy
      (PDR) was the most significant risk factor (odds ratio: 6.85; 95% CI: 2.32-20.20)
      for CAN. Eighty-three percent of patients complained of autonomic symptoms; and
      the more symptoms complained, the higher the prevalence of CAN. Impotence was the
      only single symptom associated with CAN risk. Additional CAN risks were also
      observed when patients with multiple symptoms and/or complications in
      combinations. CONCLUSIONS: Our results implied that patients with multiple
      symptoms and/or complications in combinations have increased CAN risk, and this
      may provide additional information for clinicians to identify T2DM at risk of
      having CAN.

PMID- 18824271
TI  - Safety and efficacy of inhaled human insulin (Exubera) during discontinuation and
      readministration of therapy in adults with type 1 diabetes: A 3-year randomized
      controlled trial.
AB  - OBJECTIVE: To assess pulmonary safety during discontinuation and readministration
      of inhaled human insulin (EXU; Exubera((R)) insulin human [rDNA origin])
      Inhalation Powder) therapy in adults with type 1 diabetes. METHODS: Patients were
      randomized to receive basal insulin plus either pre-meal EXU (n=290) or a short
      acting subcutaneous (SC) insulin (n=290) for 2 years (comparative phase),
      followed by 6 months of SC insulin (washout) and 6 months of their original
      therapy (readministration). Highly standardized lung function tests were
      performed throughout. RESULTS: Small treatment group differences favoring SC
      insulin in change from baseline forced expiratory volume in 1s (FEV(1)) and
      carbon monoxide diffusing capacity (DL(CO)) occurred early and were non
      progressive. These differences resolved during washout and recurred at the same
      magnitude during readministration. Both groups maintained glycemic control, and
      hypoglycemic event rates were similar. In the EXU group, insulin antibody (IAb)
      levels plateaued at 12 months, declined to near baseline levels during washout
      and increased during readministration to levels observed in the comparative
      phase. CONCLUSIONS: FEV(1) and DL(CO) changes observed during discontinuation and
      readministration of EXU therapy are consistent with a reversible, non-progressive
      and non-pathological effect on lung function. EXU readministration is not
      associated with an augmented IAb response.

PMID- 18824272
TI  - Primordial spliceosomal introns were probably U2-type.
AB  - The two types of eukaryotic spliceosomal introns, U2 and U12, possess different
      splice signals and are excised by distinct spliceosomes. The nature of the
      primordial introns remains uncertain. A comparison of the amino acid
      distributions at insertion sites of introns that retained their positions
      throughout eukaryotic evolution with the distributions for human and Arabidopsis
      thaliana U2 and U12 introns reveals close similarity with U2 but not U12. Thus,
      the primordial spliceosomal introns were, most likely, U2-type.

PMID- 18824273
TI  - Testate amoebae and nutrient cycling: peering into the black box of soil ecology.
AB  - In some areas of ecology and evolution, such as the behavioural ecology of many
      well-studied bird species, it is increasingly difficult to make surprising new
      discoveries. However, this is not the case in many areas of soil and/or microbial
      ecology. Two recent studies suggest that the testate amoebae, a microbial group
      unfamiliar to most biologists, might play a much larger role in soil nutrient
      cycling than has hitherto been suspected.

PMID- 18824274
TI  - The random dialing survey as a tool for community consultation for research
      involving the emergency medicine exception from informed consent.
AB  - STUDY OBJECTIVE: In 1996, the Food and Drug Administration and the Department of
      Health and Human Services enacted rules allowing a narrow exception from informed
      consent for critically ill patients enrolled in emergency research. These include
      requirements for community consultation prior to trial implementation. Previous
      studies have noted difficulty in engaging the community. We seek to describe the
      experience with random dialing surveys as a tool for community consultation
      across 5 metropolitan regions in the United States. METHODS: Random dialing
      surveys were used as part of the community consultation for an out-of-hospital
      clinical trial sponsored by the Resuscitation Outcomes Consortium. The survey
      method was designed to obtain a representative sample of the community according
      to population demographics and geography. Logistics of survey administration,
      role of the survey in community consultation, and survey results by population
      demographics are discussed. RESULTS: Random dialing surveys were conducted in 5
      of 8 US Resuscitation Outcomes Consortium sites. Overall, 70% to 79% of
      respondents indicated they would be willing to be enrolled in this study. Support
      for the inclusion of children (aged 15 to 18 years) ranged from 52% to 71%.
      Respondents aged 18 to 34 years were more willing to participate in the trial
      than older age groups. Women and racial minorities were less likely to favor the
      inclusion of minors. CONCLUSION: Random dialing surveys provide an additional
      tool to engage the community and obtain a sample of the opinion of the population
      about research conducted under the emergency exception from informed consent
      regulations. Similar results were obtained across 5 diverse communities in the
      United States.

PMID- 18824275
TI  - Emergency department boarding and profit maximization for high-capacity
      hospitals: challenging conventional wisdom.

PMID- 18824276
TI  - Ultrasonographically guided peripheral intravenous cannulation in emergency
      department patients with difficult intravenous access: a randomized trial.
AB  - STUDY OBJECTIVE: We seek to compare ultrasonographically guided peripheral
      intravenous access to a non-ultrasonographically guided method in a randomized
      trial of emergency department patients with difficult intravenous access.
      METHODS: A prospective cohort of patients with difficult intravenous access was
      established. Patients were randomized to 2 groups: (1) intravenous access
      obtained through an ultrasonographically guided technique or (2) intravenous
      access obtained through non-ultrasonographically guided methods. Outcomes
      measured were number of attempts after enrollment, time to cannulation from
      enrollment, and patient satisfaction. Groups were compared with nonparametric
      analysis. RESULTS: Fifty-nine patients were randomized. Twenty-eight patients
      were randomized to the ultrasonography group and 31 to the no ultrasonography
      group. A median of 2 further intravenous attempts was required in each group
      before successful cannulation, corresponding to a difference of 0 attempts (95%
      confidence interval [CI] 0 to 1 attempts). Time to cannulation showed a median of
      39 minutes in the ultrasonography group compared with 26 minutes for the no
      ultrasonography group, giving a median increase of 13 minutes for the
      ultrasonographically guided group (95% CI -5 to 28 minutes). Patients in the
      ultrasonography group had a median Likert satisfaction score of 8 compared with 7
      for the no ultrasonography group, giving a median increase of 1 on this scale in
      the ultrasonography group (95% CI 0 to 2). CONCLUSION: Ultrasonographically
      guided peripheral intravenous cannulation did not decrease the number of attempts
      or the time to successful catheterization, nor did it improve patient
      satisfaction compared with the group that did not use ultrasonography.
      Superiority of ultrasonographically guided peripheral intravenous cannulation is
      not supported by this study.

PMID- 18824277
TI  - One-year medical outcomes and emergency department recidivism after emergency
      department observation for cocaine-associated chest pain.
AB  - STUDY OBJECTIVE: Chest pain is the most common complaint among cocaine users who
      present to the emergency department (ED) seeking care, and many hospital
      resources are applied to stratify cocaine users in regard to future cardiac
      morbidity and mortality. Little is known about the longitudinal cardiac and
      noncardiac medical outcomes of cocaine users who have been stratified to an ED
      observation period after their ED visit. We examine 1-year cardiac outcomes in a
      low- to intermediate-risk sample of patients with cocaine-associated chest pain
      in an urban ED, as well as examine ED recidivism at 1 year for cardiac and
      noncardiac complaints. METHODS: Prospective consecutive cohort study of patients
      (18 to 60 years) who presented to an urban Level I ED with cocaine-associated
      chest pain and were risk stratified to low to intermediate cardiac risk.
      Exclusion criteria were ECG suggestive of acute myocardial infarction, increased
      serum cardiac markers, history of acute myocardial infarction or coronary artery
      bypass graft, hemodynamic instability, or unstable angina. Baseline interviews
      using validated measures of health functioning and substance use were conducted
      during chest pain observation unit stay and at 3, 6, and 12 months. ED
      utilization during the study year was abstracted from the medical chart. Zero
      inflated Poisson regression analyses were conducted to predict recurrent ED
      visits. RESULTS: Two hundred nineteen participants (73%) were enrolled, 65%
      returned to the ED post-index visit, and 23% returned for chest pain; of these,
      66% had a positive cocaine urine screening result. No patient had an acute
      myocardial infarction within the 1-year follow-up period. Patients with continued
      cocaine use were more likely to have a recurrent ED visit (P<.001), but these
      repeated visits were most often related to musculoskeletal pain (21%) and injury
      (30%), rather than potential cardiac complaints. CONCLUSION: Patients with
      cocaine-associated chest pain who have low to intermediate cardiac risk and
      complete a chest pain observation unit protocol have a less than 1% rate of
      myocardial infarction in the subsequent 12 months.

PMID- 18824278
TI  - Synthesis of 2-(4-substitutedmethylpiperazin-1-yl)-N-(3,4-dihydro-3-oxo-2H
      benzo[b][1,4]oxazin-7-yl)acetamides and their positive inotropic evaluation.
AB  - In an attempt to search for more potent positive inotropic agents, a series of 2
      (4-substitutedmethylpiperazin-1-yl)-N-(3,4-dihydro-3-oxo-2H-benzo[b][1,4]oxazin-7
      yl)acetamides were synthesized and their positive inotropic activities were
      evaluated by measuring left atrium stroke volume on isolated rabbit heart
      preparations. Several compounds showed favorable activities compared with the
      standard drug, milrinone, among which 2-(4-(4-methylbenzyl)piperazin-1-yl)-N-(3,4
      dihydro-3-oxo-2H-benzo[b][1,4]oxazin-7-yl)acetamide 4e showed the most potent
      activity with the 5.09+/-0.00% increased stroke volume (milrinone 1.67+/-0.64%)
      at a concentration of 1x10(-5)M in our in vitro study. The chronotropic effects
      of those compounds having significant inotropic effects were also evaluated in
      this work.

PMID- 18824279
TI  - [Guidelines for the management of uveitis in internal medicine].
AB  - In developed countries, uveitis is quite common and chronic course is associated
      with a poor visual prognosis. However, no guidelines for their management have
      been consensually proposed. Based on the experience of ophthalmologists and
      internists from tertiary care centers, this article describes the management of
      uveitis, including the diagnostic procedure, indications and types of anti
      inflammatory treatments. We focus on the interest of an exhaustive ophthalmologic
      examination for the diagnosis of an underlying systemic disease such as
      sarcoidosis. In this way, a multidisciplinary staff could be useful for an
      optimal management of uveitis. We also reviewed the main current treatments for
      severe uveitis. Whatever the origin of ocular inflammation, corticosteroids are
      consensually used as first line treatment. However, the identification of an
      underlying systemic disease helps in the refinement of further therapeutic
      choices. In cases of refractory and sight threatening uveitis, the short-term use
      of infliximab, a chimeric anti-TNF-alpha antibody, has been shown to be effective
      and safe. These recommendations do not constitute treatment guidelines but aim at
      improving the uniformity of clinical practice for the management of uveitis,
      until higher levels of evidence are obtained.

PMID- 18824280
TI  - [Lower limb edema during normal pressure hydrocephalus].

PMID- 18824281
TI  - Inhibitory effect of olive oil on fibrosis induced by carbon tetrachloride in rat
      liver.
AB  - BACKGROUND & AIMS: In this study, the inhibitory effect of olive oil on liver
      fibrosis induced by carbon tetrachloride (CCl(4)) has been investigated in rats.
      METHODS: Rats were divided randomly into four groups: control, CCl(4), and two
      olive oil groups. Except for rats in the control group, all rats were orally
      administered CCl(4) twice a week for 8 weeks. Rats in the olive oil groups were
      treated daily with olive oil (2 or 10 ml/kg) through gastrogavage for the entire
      experimental period. RESULTS: RT-PCR analysis showed that CCl(4) increased the
      hepatic mRNA expressions of lipopolysaccharide binding protein, CD14, Toll-like
      receptor-4, NADPH oxidase, nuclear factor-kappa beta, collagen (alpha1) (I),
      collagen (alpha1) (III), and transforming growth factor beta1. The expression of
      these mRNAs could be decreased by olive oil treatment. In addition, Western blot
      analysis also supported these results. CCl(4)-induced liver damage, as
      characterized by the increase in hepatic malondialdehyde and hydroxyproline
      levels. Olive oil treatment decreased the hepatic malondialdehyde and
      hydroxyproline levels. Histological evaluations showed that olive oil could
      attenuate the liver fibrosis, necrosis, and expression of smooth muscle alpha
      actin that are induced by CCl(4). CONCLUSION: It is speculated that the phenolic
      compounds in olive oil significantly reduced CCl(4)-induced hepatic fibrosis in
      rats.

PMID- 18824282
TI  - Soil acidification and foliar nutrient status of Ontario's deciduous forest in
      1986 and 2005.
AB  - To assess the impacts of the decline in sulphur (S) deposition over the past 20
      years in Ontario, soil chemistry and sugar maple (Acer saccharum Marsh) foliar
      chemistry were measured at 17 sites in south and central Ontario in 2005 and
      compared with archived samples collected in 1986. Foliar S concentrations were
      lower in 2005, reflecting the decline in S deposition whereas foliar N remained
      unchanged, reflecting the lack of change in N deposition in Ontario. Mineral soil
      pH, exchangeable base cations were lower in 2005 whereas total S, N and cation
      exchange capacity (CEC) were unchanged. Foliar concentrations of Ca were
      positively related to soil Ca levels in the A-horizon and were lower in 2005.
      Despite evidence of increasing soil acidity and losses of calcium, foliar base
      cation concentrations at most sites were adequate for sugar maple and forest
      health in terms of canopy appearance (Decline Index) improved.

PMID- 18824283
TI  - Sorption of alkylphenols on Ebro River sediments: comparing isotherms with field
      observations in river water and sediments.
AB  - This study reports sorption isotherms of the endocrine disruptors nonylphenol
      (NP) and octylphenol (OP) in three sediment samples from the Ebro River basin (NE
      Spain), with organic carbon fractions (f(OC)) ranging from 0.0035 to 0.082
      g(OC)g(-1). All isotherms were fitted to the Freundlich model with slightly
      nonlinear exponents ranging from 0.80 to 0.94. The solubility of the compounds as
      well as the organic carbon (OC) content had the strongest influences on the
      sorption behavior of these compounds. Comparison of the laboratory-spiked samples
      with the native contamination of NP of 45 water and concurrent sediment samples
      resulted in reasonable matches between both data sets, even though the lowest
      concentrations in the field were not completely reached in laboratory tests. This
      good agreement indicates that sorption laboratory data can be extrapolated to
      environmental levels and therefore the distribution of nonylphenol between
      sediments and water can be predicted with a precision of one order of magnitude.
      Furthermore, laboratory experiments with simultaneous loading of NP and OP
      revealed negligible competition for sorption sites at low concentrations.

PMID- 18824284
TI  - C60 fullerene: a powerful antioxidant or a damaging agent? The importance of an
      in-depth material characterization prior to toxicity assays.
AB  - Since the discovery of fullerenes in 1985, these carbon nanospheres have
      attracted attention regarding their physico/chemical properties. Despite little
      knowledge about their impact on the environment and human health, the production
      of fullerenes has already reached an industrial scale. However, the toxicity of
      C(60) is still controversially discussed. The aim of this study was to clarify
      the biological effects of tetrahydrofuran (THF) suspended C(60) fullerene in
      comparison to water stirred C(60) fullerene suspensions. Beyond that, we analyzed
      the effects on the Crustacea Daphnia magna an indicator for ecotoxicological
      effects and the human lung epithelial cell line A549 as a simplified model for
      the respiratory tract. We could demonstrate that water-soluble side products
      which were formed in THF nC(60) suspension were responsible for the observed
      acute toxic effects, whereas fullerenes themselves had no negative effect
      regardless of the preparative route on either A549 cell in vitro or D. magna in
      vivo.

PMID- 18824285
TI  - Synthetic TiO2 nanoparticle emission from exterior facades into the aquatic
      environment.
AB  - We present direct evidence of the release of synthetic nanoparticles from urban
      applications into the aquatic environment. We investigated TiO(2) particles as
      these particles are used in large quantities in exterior paints as whitening
      pigments and are to some extent also present in the nano-size range. TiO(2)
      particles were traced from exterior facade paints to the discharge into surface
      waters. We used a centrifugation based sample preparation which recovers TiO(2)
      particles between roughly 20 and 300nm. Analytical electron microscopy revealed
      that TiO(2) particles are detached from new and aged facade paints by natural
      weather conditions and are then transported by facade runoff and are discharged
      into natural, receiving waters. Microscopic investigations are confirmed by bulk
      chemical analysis. By combining results from microscopic investigations with bulk
      chemical analysis we calculated the number densities of synthetic TiO(2)
      particles in the runoff.

PMID- 18824286
TI  - Crescentic glomerulonephritis associated with hypocomplementemic urticarial
      vasculitis syndrome.

PMID- 18824287
TI  - The association of race with erythropoietin dose in patients on long-term
      hemodialysis.
AB  - BACKGROUND: Medicare data indicate that black hemodialysis patients receive
      greater doses of erythropoietin (EPO) than white patients when achieving similar
      hemoglobin levels. We confirmed and evaluated this observed association between
      race and EPO dose. STUDY DESIGN: Cross-sectional cohort study. SETTING &
      PARTICIPANTS: Primary Medicare-insured white (57%) and black (43%) adult long
      term hemodialysis patients treated by Fresenius Medical Care who received EPO
      from January 1 to 31, 2004 (N = 44,721). PREDICTOR: White/black race. OUTCOMES:
      Average weekly EPO dose. MEASUREMENTS: Associations between race and baseline
      demographic and laboratory variables were evaluated by using logistic and linear
      regression models. Correlates of log-transformed weekly EPO dose were determined
      using linear regression models. RESULTS: Black patients received 12.6% more EPO
      than white patients (95% limits, 10.9% to 14.3%; P < 0.001). This racial
      difference in EPO dose was observed across similar hemoglobin levels despite
      fewer catheters (P < 0.001) and fewer prior hospitalization events in black
      patients (P = 0.002). Black patients were younger and had larger body size and
      greater albumin and biointact parathyroid hormone levels, but lower equilibrated
      Kt/V and white blood cell counts (all P < 0.001). In the 95th percentile of EPO
      dose (those receiving > 60,000 U/wk), there was a greater proportion of black
      patients (6% of total black population compared with only 4% in all white
      patients; P < 0.001). The difference in EPO dose between black and white patients
      was modified by age and was significant at ages younger than 45 and 65 years or
      older. LIMITATIONS: Observational study limited to white and black adult Medicare
      patients only, correlating with EPO doses from a single month, without adjustment
      for comorbid conditions. CONCLUSIONS: Black patients were administered
      approximately 12% greater EPO doses than white patients while achieving similar
      hemoglobin levels. We identified variables that differed across race that may
      explain this difference, but they were either not actionable or presented limited
      opportunity for intervention. Additional studies are needed to define a
      physiological (or pathological) basis for these observations.

PMID- 18824288
TI  - Safety of ferumoxytol in patients with anemia and CKD.
AB  - BACKGROUND: Iron deficiency anemia is a common complication in patients with
      chronic kidney disease (CKD). Currently available intravenous (IV) iron
      replacement therapies have either inconvenient regimens of administration or
      adverse event profiles that limit their utility in the outpatient setting.
      Ferumoxytol is a novel, semisynthetic, carbohydrate-coated, superparamagnetic
      iron oxide nanoparticle that is administered IV as an injection. The main
      objective of this study was to assess the safety of ferumoxytol for the treatment
      of patients with CKD stages 1 to 5 and 5D. STUDY DESIGN: Phase 3, randomized,
      double-blind, placebo-controlled, crossover, multicenter study of a single 510-mg
      dose of ferumoxytol versus saline as placebo. SETTING & PARTICIPANTS: 750
      patients with CKD stages 1 to 5 and 5D. INTERVENTION: An IV injection of either
      17 mL of ferumoxytol or saline placebo over 17 seconds on day 0 and the alternate
      agent on day 7. OUTCOMES & MEASUREMENTS: Descriptive comparison of adverse
      events, laboratory tests, and vital signs. RESULTS: Of 750 randomly assigned
      patients with CKD, 60% were not on dialysis therapy. 713 patients received
      ferumoxytol, and 711 received placebo. There were 420 adverse events reported;
      242 in 152 patients (21.3%) with ferumoxytol and 178 in 119 patients (16.7%) with
      placebo. The incidence of related adverse events was 5.2% with ferumoxytol and
      4.5% with placebo. The most common related adverse events after each treatment
      included symptoms related to the injection/infusion site, dizziness, pruritus,
      headache, fatigue, and nausea. Serious adverse events occurred in 21 patients
      (2.9%) after ferumoxytol and 13 patients (1.8%) after placebo. Serious related
      adverse events were observed in 1 patient (0.1%) after each treatment. There was
      no meaningful decrease in blood pressure after administration of ferumoxytol or
      placebo. LIMITATIONS: Follow-up was 7 days after each study treatment.
      CONCLUSIONS: Ferumoxytol is well tolerated and has a safety profile similar to
      placebo in anemic patients with CKD stages 1 to 5 and 5D.

PMID- 18824289
TI  - Association of changes in bone remodeling and coronary calcification in
      hemodialysis patients: a prospective study.
AB  - BACKGROUND: Vascular calcification is common and constitutes a prognostic marker
      of mortality in the hemodialysis population. Derangements of mineral metabolism
      may influence its development. The aim of this study is to prospectively evaluate
      the association between bone remodeling disorders and progression of coronary
      artery calcification (CAC) in hemodialysis patients. STUDY DESIGN: Cohort study
      nested within a randomized controlled trial. SETTING & PARTICIPANTS: 64 stable
      hemodialysis patients. PREDICTOR: Bone-related laboratory parameters and bone
      histomorphometric characteristics at baseline and after 1 year of follow-up.
      OUTCOMES: Progression of CAC assessed by means of coronary multislice tomography
      at baseline and after 1 year of follow-up. Baseline calcification score of 30
      Agatston units or greater was defined as calcification. Change in calcification
      score of 15% or greater was defined as progression. RESULTS: Of 64 patients, 38
      (60%) of the patients had CAC and 26 (40%) did not [corrected]. Participants
      without CAC at baseline were younger (P < 0.001), mainly men (P = 0.03) and
      nonwhite (P = 0.003), and had lower serum osteoprotegerin levels (P = 0.003) and
      higher trabecular bone volume (P = 0.001). Age (P = 0.003; beta coefficient =
      1.107; 95% confidence interval [CI], 1.036 to 1.183) and trabecular bone volume
      (P = 0.006; beta coefficient = 0.828; 95% CI, 0.723 to 0.948) were predictors for
      CAC development. Of 38 participants who had calcification at baseline, 26 (68%)
      had CAC progression in 1 year. Progressors had lower bone-specific alkaline
      phosphatase (P = 0.03) and deoxypyridinoline levels (P = 0.02) on follow-up, and
      low turnover was mainly diagnosed at the 12-month bone biopsy (P = 0.04). Low
      turnover bone status at the 12-month bone biopsy was the only independent
      predictor for CAC progression (P = 0.04; beta coefficient = 4.5; 95% CI, 1.04 to
      19.39). According to bone histological examination, nonprogressors with initially
      high turnover (n = 5) subsequently had decreased bone formation rate (P = 0.03),
      and those initially with low turnover (n = 7) subsequently had increased bone
      formation rate (P = 0.003) and osteoid volume (P = 0.001). LIMITATIONS:
      Relatively small population, absence of patients with severe hyperparathyroidism,
      short observational period. CONCLUSIONS: Lower trabecular bone volume was
      associated with CAC development, whereas improvement in bone turnover was
      associated with lower CAC progression in patients with high- and low-turnover
      bone disorders. Because CAC is implicated in cardiovascular mortality, bone
      derangements may constitute a modifiable mortality risk factor in hemodialysis
      patients.

PMID- 18824292
TI  - HDAC family: What are the cancer relevant targets?
AB  - Histone deacetylases comprise a family of 18 genes, which are grouped into
      classes I-IV based on their homology to their respective yeast orthologues.
      Classes I, II, and IV consist of 11 family members, which are referred to as
      "classical" HDACs, whereas the 7 class III members are called sirtuins. Classical
      HDACs are a promising novel class of anti-cancer drug targets. First HDAC
      inhibitors have been evaluated in clinical trials and show activity against
      several cancer diseases. However, these compounds act unselectively against
      several or all 11 HDAC family members. As a consequence, clinical phase I trials
      document a wide range of side effects. Therefore, the current challenge in the
      field is to define the cancer relevant HDAC family member(s) in a given tumor
      type and to design selective inhibitors, which target cancer cells but leave out
      normal cells. Knockout of single HDAC family members in mice produces a variety
      of phenotypes ranging from early embryonic death to viable animals with only
      discrete alterations, indicating that potential side effects of HDAC inhibitors
      depend on the selectivity of the compounds. Recently, several studies have shown
      that certain HDAC family members are aberrantly expressed in several tumors and
      have non-redundant function in controlling hallmarks of cancer cells. The aim of
      this review is to discuss individual HDAC family members as drug targets in
      cancer taking into consideration their function under physiological conditions
      and their oncogenic potential in malignant disease.

PMID- 18824293
TI  - Inhibition of mTOR enhances chemosensitivity in hepatocellular carcinoma.
AB  - The present study investigated the effect of mammalian target of rapamycin (mTOR)
      inhibition on HCC cells in vitro and in vivo, either alone or in combination with
      cytotoxic agents. In vitro, HCC cell lines were exposed to RAD001, an mTOR
      inhibitor, either alone or in combination with cisplatin. Alone, RAD001
      suppressed cell proliferation in all cell lines tested, but did not induce
      apoptosis. RAD001 in combination with cisplatin induced a significant increase in
      the number of apoptotic cells, downregulated the expression of pro-survival
      molecules, Bcl-2, survivin and cyclinD1, and increased the cleavage of PARP,
      compared to RAD001 or cisplatin alone. Transfection of p53 into the Hep3B cell
      line increased the sensitivity of tumor cells to cisplatin. The suppression of
      HCC tumor growth in vivo was enhanced by RAD001 combined with cisplatin,
      accompanied by a significant increase in the number of apoptotic cells in tumor
      tissues. This study demonstrates that inhibition of mTOR suppresses tumor growth
      and sensitizes tumor cells to chemocytotoxic agents.

PMID- 18824294
TI  - Quantitative detection of survivin in malignant pleural effusion for the
      diagnosis and prognosis of lung cancer.
AB  - In the present study, pleural effusions are the first time to be used as the
      specimens for detection of survivin expression in lung cancer patients. We
      demonstrated that by quantifying survivin expression with enzyme-linked
      immunosorbent assay (ELISA) in the 80 effusion samples exhibited a diagnostic
      power of 85% and 75% in sensitivity and specificity, respectively. A multivariate
      analysis with the Cox regression model revealed that both high survivin
      expression and cancer cells of stage IV were the indicators for poor prognosis of
      lung cancer. In conclusion, quantitative assay of survivin in pleural effusion
      could be useful both in diagnosis and prognosis for lung cancer.

PMID- 18824295
TI  - Effect of fly ash preliminary calcination on the properties of geopolymer.
AB  - The influence of preliminary calcination of fly ashes on the geopolymerisation
      process has been studied. Preliminary calcination at 500 and 800 degrees C causes
      decarbonation of the fly ash while it also leads to a decrease of the amorphous
      content of the fly ashes from 60 to 57%. Geopolymer prepared using raw fly ash
      exhibited a compressive strength 55.7(9.2)MPa, while for 500 and 800 degrees C
      calcined samples it reduced to 54(5.8) and 44.4(5.4)MPa, respectively. The
      decrease in compressive strength of the geopolymers is discussed in terms of
      partial surface crystallisation of the fly ash particles. Reactivity of the fly
      ash also has been correlated with the shrinkage rate and presence of
      efflorescence on the surface of geopolymers.

PMID- 18824296
TI  - Ametryn degradation in the ultraviolet (UV) irradiation/hydrogen peroxide (H2O2)
      treatment.
AB  - Ultraviolet (UV) irradiation (253.7nm) in the presence of hydrogen peroxide
      (H(2)O(2)) was used to decompose aqueous ametryn. The concentrations of ametryn
      were measured with time under various experiment conditions. The investigated
      factors included H(2)O(2) dosages, initial pH, initial ametryn concentrations,
      and a variety of inorganic anions. Results showed that ametryn degradation in
      UV/H(2)O(2) process was a pseudo-first-order reaction. Removal rates of ametryn
      were greatly affected by H(2)O(2) dosage and initial concentrations of ametryn,
      but appeared to be slightly influenced by initial pH. Furthermore, we
      investigated the effects of four anions (SO(4)(2-), Cl(-), HCO(3)(-), and CO(3)(2
      )) on ametryn degradation by UV/H(2)O(2). The impact of SO(4)(2-) seemed to be
      insignificant; however, Cl(-), HCO(3)(-), and CO(3)(2-) considerably slowed down
      the degradation rate because they could strongly scavenge hydroxyl radicals (OH)
      produced during the UV/H(2)O(2) process. Finally, a preliminary cost analysis
      revealed that UV/H(2)O(2) process was more cost-effective than the UV alone in
      removal of ametryn from water.

PMID- 18824297
TI  - Anaerobic biodegradation of hexazinone in four sediments.
AB  - Anaerobic biodegradation of hexazinone was investigated in four sediments (L1,
      L2, Y1 and Y2). Results showed that the L2 sediment had the highest
      biodegradation potential among four sediments. However, the Y1 and Y2 sediments
      had no capacity to biodegrade hexazinone. Sediments with rich total organic
      carbon, long-term contamination history by hexazinone and neutral pH may have a
      high biodegradation potential because the former two factors can induce the
      growth of microorganisms responsible for biodegradation and the third factor can
      offer suitable conditions for biodegradation. The addition of sulfate or nitrate
      as electron acceptors enhanced hexazinone degradation. As expected, the addition
      of electron donors (lactate, acetate or pyruvate) substantially inhibited the
      degradation. In natural environmental conditions, the effect of intermediate A [3
      (4-hydroxycyclohexyl)-6-(dimethylamino)-1-methyl-1,3,5-triazine-2,4(1H, 3H)dione]
      on anaerobic hexazinone degradation was negligible because of its low level.

PMID- 18824298
TI  - Removal of sodium lauryl sulphate by coagulation/flocculation with Moringa
      oleifera seed extract.
AB  - Among other natural flocculant/coagulant agents, Moringa oleifera seed extract
      ability to remove an anionic surfactant has been evaluated and it has been found
      to be very interesting. Sodium lauryl sulphate was removed from aqueous solutions
      up to 80% through coagulation/flocculation process. pH and temperature were found
      to be not very important factors in removal efficiency. Freundlich (F), Frumkin
      Fowler-Guggenheim (FFG) and Gu-Zhu (GZ) models were used to adjust experimental
      data in a solid-liquid adsorption hypothesis. Last one resulted to be the most
      accurate one. Several data fit parameters were determined, as Freundlich order,
      which was found to be 1.66, Flory-Huggins interaction parameter from FFG model,
      which was found to be 4.87; and limiting Moringa surfactant adsorption capacity
      from GZ model, which was found to be 2.13 x 10(-3)mol/g.

PMID- 18824299
TI  - Developing sulfide-oxidizing biofilm on H2S-exhausted carbon for sustainable bio
      regeneration and biofiltration.
AB  - The feasibility of developing biofilm on exhausted carbon using pre-deposited
      sulfur compounds as the sole energy source was studied, aiming to re-use them in
      odor biofiltration. The exhausted carbon with different properties, including
      surface pH, sulfur content and porosity, was used. A series of off-line trials
      were conducted to investigate the release of sulfur compounds from the exhausted
      carbon and the attachment of sulfide-oxidizing bacteria on the exhausted carbon.
      Without any pre-treatment, a few bacteria attachment on exhausted carbon was
      observed by SEM, due to possibly the limitation of reduced sulfur compounds
      release for bacterial growth. The biofilm development was much improved by adding
      NaOH solution to partially pre-desorb the deposited sulfur into liquid phase,
      which provided initial energy for bacterial growth. With the attached bacteria,
      the further significant release of the deposited sulfur was achieved through an
      additional driving force: biodegradation. The key issues for developing biofilm
      on exhausted carbon were concluded, which mainly concerned of desorption of pre
      deposited reduced sulfur compounds and porosity of carbon. The sulfur-associated
      reactions occurring in developing biofilm on exhausted carbon was proposed. Bio
      regeneration of exhausted carbon in the course of biofilm development was also
      preliminarily assessed.

PMID- 18824300
TI  - The effectiveness of ferrous iron and sodium dithionite for decreasing resin
      extractable Cr(VI) in Cr(VI)-spiked alkaline soils.
AB  - Ferrous iron, Na(2)S(2)O(4), and a mixture of Fe(II) and Na(2)S(2)O(4) (4:1
      mol/mol) were tested for their effectiveness for decreasing resin-extractable
      Cr(VI) in alkaline Cr(VI)-spiked soils. The results indicated that adding those
      reductants greatly decreased the amount of resin-extractable Cr(VI) when the
      application rate of reductants equaled the number of equivalents of dichromate
      added to the Cr(VI)-spiked soils. This was mainly as a result of the Cr(VI)
      reduction into Cr(III), as supported by the XANES spectra. Among the tested
      reductants, a mixture of Fe(II) and Na(2)S(2)O(4) was the most effective to
      decrease resin-extractable Cr(VI). The extent to which resin-extractable Cr(VI)
      and soil pH were decreased was affected by the pH of the reductants. Among the
      tested reductants at various pH, FeSO(4) at pH below 1 was the most effective in
      decreasing resin-extractable Cr(VI) in alkaline soils. However, the soil pH was
      the most decreased as well. On the other hand, the mixtures of ferrous iron and
      dithionite at a wide range of pH were all efficient (>70% efficiency) in
      decreasing resin-extractable Cr(VI). Moreover, the extent of the decrease in soil
      pH was much smaller than that by FeSO(4) (pH<1) alone, and thus the possibility
      of the Cr(III) hazard can be avoided.

PMID- 18824301
TI  - The Chronic Pain Acceptance Questionnaire: confirmatory factor analysis and
      identification of patient subgroups.
AB  - Over the past decade, the importance of acceptance of chronic pain has been
      demonstrated. Acceptance has often been assessed using the 20-item, two-factor
      Chronic Pain Acceptance Questionnaire (CPAQ; McCracken, Vowles, Eccleston, Pain
      2004;107:159-66). This two-factor model has been supported but awaits further
      confirmation. The present investigation sought to address this issue in two large
      samples of pain suffers. Exploratory factor analyses (N=333) examined a number of
      solutions, ranging from two to five factors. Evaluation indices provided clear
      support for a 20-item, two-factor solution. Confirmatory factor analyses, using
      the second sample (N=308), examined a number of models. Fit indices demonstrated
      that the model identified in the exploratory analyses had the best fit. Finally,
      a series of cluster analyses were performed using a combined sample (N=641).
      Results indicated three clusters: one with high scores on both subscales (n=146),
      one with low scores on both subscales (n=239), and one with discrepant scores
      that were high on the Activity Engagement subscale and low on the Pain
      Willingness subscale (n=286). Follow-up analyses indicated significant
      differences among the clusters across multiple measures of functioning. The
      cluster with low CPAQ scores reported more difficulties in comparison to the
      group with high scores, while the group with discrepant CPAQ scores generally
      reported difficulties that fell in between. These results provide further support
      for the 20-item, two-factor CPAQ and indicate that it is both theoretically and
      practically useful.

PMID- 18824302
TI  - Targeting treatment for non-specific musculoskeletal pain.

PMID- 18824303
TI  - Back to the future: developing hypotheses on the effects of climate change on
      ovine parasitic gastroenteritis from historical data.
AB  - Although the influence of temperature and moisture on the free-living stages of
      gastrointestinal nematodes has been described in detail, and evidence for global
      climate change is mounting, serious attempts to relate altered incidence or
      seasonal patterns of disease to climate change are lacking. In Great Britain,
      veterinary surveillance laboratory diagnoses of ovine parasitic gastroenteritis
      (PGE) have been categorised in species groups and recorded since 1975. Here we
      present a detailed analysis of these historical data. Over the past 5-10 years,
      highly significant increases in the overall rate of diagnosis of PGE were
      observed for all species categories. After identifying and analysing possible
      sources of bias, the effect of climate change on parasite epidemiology proved the
      most likely explanation for the observed patterns, although other hypotheses
      could not be refuted. Seasonal rates of diagnosis suggest that, in line with
      increases in temperature, fewer larvae of Teladorsagia and Trichostrongylus
      species survive the winter and spring at pasture, while the windows of
      transmission of these species, and of Haemonchus contortus, have extended into
      the autumn. For all species categories significant differences in rates of
      diagnosis, and in the seasonality of disease, were identified between regions.
      Nematodirosis showed a pronounced peak in spring and early summer in Scotland
      while in the Southwest, where fewer diagnoses were made, it also appeared
      regularly at other times of year. The data presented serve as a baseline against
      which future changes can be measured.

PMID- 18824305
TI  - Bovine and human-derived passive immunization could help slow a future avian
      influenza pandemic.
AB  - An epidemic of human transmitted avian influenza could have casualties on a scale
      seen in the great Spanish influenza pandemic of 1918. This paper proposes that
      should such occur before effective vaccines and antiviral drugs are available,
      the outbreak could be significantly slowed by consumption of raw milk produced by
      herds of pathogen-free lactating cows intranasally inoculated with heat
      sterilized sputa pooled from avian influenza patients, supplemented by parenteral
      serum immune globulin from the same cows. Efficiency of bovine antibody
      production could be enhanced using cholera toxin subunit b, and milk production
      could be rapidly accelerated using recombinant bovine somatotropin hormone. In
      this way, it would be possible to quickly create and distribute large quantities
      of milk-based and serum-based passive immune globulin active against the strains
      of avian influenza present in a particular geographic area and gain time for
      production of human convalescent plasma and other public health measures. This
      novel approach might also have utility for other serious respiratory infectious
      diseases, including non-avian influenza, SARS, hantavirus, respiratory syncytial
      virus, antibiotic-resistant Streptococcus pneumoniae and pneumonia-causing
      Staphylococcus aureus.

PMID- 18824304
TI  - Vertical migration of Haemonchus contortus third stage larvae on Brachiaria
      decumbens grass.
AB  - The present study aimed at evaluating the vertical migration of Haemonchus
      contortus third stage larvae (L3) on Brachiaria decumbens grass, as well as at
      verifying whether larval numbers on pasture varies over the day due to climatic
      conditions. Feces containing H. contortus L3 were deposited on the soil in the
      middle of herbage which was initially 30 cm high. Seven days later, samples of
      different herbage strata (0-10, 10-20 and >20 cm), remaining feces and a layer of
      approximately 1cm soil were collected. Tests were carried out in four periods:
      September 2006, December 2006, March 2007, and June 2007. Samples were collected
      at sunrise, mid-day, sunset, and mid-night. The humidity and temperature
      conditions observed in different months influenced larval migration from the
      feces to the grass. In September, December and March, it rained after fecal
      deposition on pasture, which favored migration of larvae from the feces to the
      herbage. Conversely, in June 2007, when there was no rainfall after fecal
      deposition and temperatures were lower, L3 were mainly recovered from feces. As
      regards the vertical migration of larvae, the numbers of H. contortus L3 in the
      forage strata remained relatively constant over the day. This indicates there is
      not a determined period in which sheep on pasture are at higher risk of
      infection. Finally, in all collection periods a considerable amount of third
      stage larvae was observed on the herbage top, which is the first plant part
      consumed by sheep.

PMID- 18824306
TI  - [Update on the progestin-only contraception].
AB  - Despite the lack of complete data concerning their effects, the use of progestin
      only contraception is increasing in France (particularly the intra-uterine
      device, the subdermal implantation, and microprogestins). These prescriptions
      include a broad range of molecules and administration of doses. In some cases,
      prescriptions of progestogens are made out of the marketing authorisation
      indications (especially for macroprogestins). For all of these reasons, an Expert
      Advisory Board has been set up in order to answer the 35 questions addressed by
      an Expert Organization Board. The choice of these questions was based on
      controversial or nonconsensual points usually encountered in everyday clinical
      practice. When possible, answers given were strongly supported by data issued
      from medical literature. In situations where clinical studies were lacking, the
      Expert Advisory Board answered in the most consensual way. All answers given by
      the Expert Advisory Board were subsequently submitted to the Expert Assessment
      Board before the latest validation of this document. The progestogen only
      contraception has different levels of action (local and/or central) which may
      vary from one drug to another. Its prescription is granted satisfactory efficacy
      (the macroprogestins' efficacy has never been evaluated) but requires a strict
      pill-taking routine (especially for the microprogestin contraception). It has
      never been demonstrated that the use of progestogen is associated with an
      increased risk of breast cancer. Nevertheless, analysis of breast cancer and
      progestogen studies should be carried out carefully. Even though the effects,
      often misunderstood, of the different progestogens on mineral bone density are
      likely to vary according to the molecules, in particular due to the plasma
      estradiol level, there is no direct argument for considering the progestin only
      contraception as a fracture risk factor. As for the venous thromboembolism risk,
      progestogens are not considered to be risk factors. The progestogen only
      contraception is advised in the following cases: bad tolerance of exogenous
      oestrogens; in order to counteract an endogenous hyperoestrogenosis; metabolic or
      cardiovascular contraindications to estroprogestin; hormonal fluctuations
      generating premenstrual dysphoria or catamenial headaches. Lastly, the progestin
      only contraception should be used as a prime contraception in some particular
      situations (breast feeding, adenomyosis...).

PMID- 18824307
TI  - [Comparison of three enzyme immunoassays for detection of Clostridium difficile
      toxins A and B].
AB  - AIM OF THE STUDY: Diagnosis of Clostridium difficile-associated diarrhea is
      classically based on detection of toxin A and/or toxins A+B by using several
      techniques. However, these techniques show important differences in terms of
      sensitivity and specificity. In this work, we compared three commercial
      immunoenzymatic tests for detecting C. difficile toxins. METHODS: We used three
      immunoenzymatic techniques: ELISA Premiertrade mark Toxins A and B (Meridian),
      ImmunoCard (IC) Toxins A and B (Meridian), and Triage (TRI) Antigen GDH and Toxin
      A (Biosite). Culture on the specific media C. difficile (bioMerieux) was
      performed in parallel. RESULTS: During two years, 898 stool specimens have been
      tested by using the three different techniques. According to the manufacturer's
      recommendations (sample positive if optical density [OD] value greater or equal
      to 0.15), 205 (22.8%) were positive for ELISA. Among them, 65 (31.7%) were
      negative for all other tests, and they have been considered as false-positive
      results. This discrepancy led us to choose other OD values (greater than 0.75:
      positive result; 0.15-0.75: limit result). For limit results, IC, TRI, antigen
      GDH, and culture methods were positive in 30, 2, 41, and 29% of cases,
      respectively, whereas for positive results (>0.75), they were positive in 82, 54,
      84, and 76% of cases, respectively. CONCLUSION: ELISA and IC tests are the most
      powerful and are concordant together if interpretation is performed with OD
      values redefined by the microbiology laboratory. The choice of the technique to
      use depends on the number of samples to analyze, the rapidity of the result, and
      the cost.

PMID- 18824308
TI  - [Testing of a new probe 16/18/45 Hybrid Capture (Digene) in women with high risk
      HPV infection].
AB  - BACKGROUND: HPV HR detection test are needed when ASCUS is diagnosed on Pap test.
      The risk of progression to cervical cancer is dependant on the HPV genotype and
      three types (HPV 16, 18 and 45) are found in 77.4% of the cervical cancer. Here
      we have tested a new probe 16/18/45 (Digene) that is able to detect specifically
      these three types. MATERIAL AND METHODS: Thirty-seven women with a Hybrid Capture
      2 High Risk test (Digene) positive were selected to test the new probe 16/18/45.
      Samples were typed using sequencing reaction after GP5+/GP6+ PCR. Types were
      given after comparison with the GenBank. Discordant results were controlled with
      Inno-Lipa HPV genotyping v2 test (Innogenetics). RESULTS: Among the 37 women with
      HR HPV result, 48.6% were positive with the probe 16/18/45 (18 patients). After
      genotyping, 12 results were concordant and six discordant (three HPV 31, two HPV
      58 et one HPV 59). For the other 19 patients with negative result, 18 are
      concordant and one discordant (HPV 18). Global concordance for typing between
      this probe and sequencing was 81% with a kappa test of 0.62 that means a good
      concordance. Positive predictive value is 66.6% and negative predictive value is
      94.7%. CONCLUSION: This study shows a good efficiency of the 16/18/45 probe to
      detect the genotypes that have the higher risk of progression to cervical cancer.
      This probe could also allow to follow the epidemiology of HR HPV infection after
      a large use of HPV vaccines.

PMID- 18824309
TI  - [Emergent viruses, a continuous challenge].

PMID- 18824310
TI  - [Inhibition of bacterial adhesion and prevention of biofilm formation: Use of
      organic self-assembled monolayers on inorganic surfaces].
AB  - Implant related nosocomial infections are a serious public health concern.
      Colonisation by contaminating bacteria of the bare implant surface may lead to
      the formation of a biofilm protecting bacteria against host defences and
      antibiotics. To decrease the risk of infection, a strategy is to modify the
      biomaterial surface by an antibacterial coating, inhibiting bacterial adhesion
      ("passive" coatings) or able to kill bacteria ("active" coatings). This article
      describes the potential of self-assembled monolayers as antibacterial coatings
      allowing the molecular level control of the surface properties of inorganic
      substrates. After a presentation of the compounds used to form self-assembled
      monolayers, we present the literature dealing with antibacterial monolayers and
      the latest developments concerning "active" phosphonate monolayers that
      significantly inhibit the growth of bacterial biofilm.

PMID- 18824311
TI  - Benzodiazepine use among opiate-dependent subjects in buprenorphine maintenance
      treatment: correlates of use, abuse and dependence.
AB  - BACKGROUND: Previous studies from North America, Europe and Australia have
      reported high levels of benzodiazepine use among opiate-dependent patients in
      opiate maintenance treatment. However, to date, there are no available data on
      patterns of abuse and dependence on benzodiazepines according to DSM criteria
      among these patients. AIMS: To describe the independent correlates of use, abuse
      and dependence on benzodiazepines among buprenorphine patients selected from
      standard treatment settings. METHODS: Cross-sectional study in France between
      June 2001 and June 2004. Buprenorphine patients treated for over 3 months were
      recruited via physicians prescribing buprenorphine. Patients answered a self
      administered questionnaire, the DSM-IV criteria for benzodiazepine abuse and
      dependence, the Beck Anxiety and Depression Inventories (BAI, BDI) and the
      Nottingham Health Profile (NHP). Main outcome was modalities of benzodiazepine
      use: no use vs. simple use vs. problematic use (abuse or dependence according to
      DSM-IV). RESULTS: 170 patients were recruited. 54% did not use benzodiazepines
      during the previous month, 15% were simple users and 31% were problematic users.
      Benzodiazepine use (all modalities) was associated with poly-use of
      psychotropics. Simple users of benzodiazepines were not statistically different
      from non-users for the other factors explored. Problematic users of
      benzodiazepines had higher depression and anxiety levels, correlated with quality
      of life impairment and precariousness. They used higher dosages of
      benzodiazepines than simple users. CONCLUSIONS: Characteristics of simple
      benzodiazepine users were distinct from problematic users but not from non-users
      in this sample of buprenorphine patients. This should be taken into account in
      the clinical management of benzodiazepine use among buprenorphine patients.

PMID- 18824312
TI  - PCR-sequence characterization of new adenoviruses found in reptiles and the first
      successful isolation of a lizard adenovirus.
AB  - A consensus nested PCR was used to screen diagnostic samples from approximately
      70 reptiles for the presence of adenoviruses (AdV) in the years 2006-2007.
      Classical virus isolation methods were also used with all samples. After
      adenoviruses were detected in a group of helodermatid lizards in a Danish zoo, a
      follow-up study was also carried out on lizards from this group (10 Mexican
      beaded lizards and 24 Gila monsters) over the period of a year. Adenoviruses were
      detected in a total of 26 lizards and snakes by PCR. The PCR amplicons from all
      positive animals were sequenced and the resulting polymerase gene sequences were
      used for phylogenetic analysis. Altogether six Agamid AdVs were amplified, with a
      minimal sequence variation between one another and between these and GenBank
      Agamid AdVs. The sequence obtained from one of the Gila monsters is identical
      with the GenBank Helodermatid AdV, while the sequences from the Mexican beaded
      lizards differ from this. In a snake collection we have detected a new AdV from
      an Asp viper. All of the above mentioned adenoviruses cluster in the Atadenovirus
      genus. However, the sequence from a new Varanid AdV detected in this study
      clusters outside this genus. On cell culture, viruses were isolated from three of
      the AdV positive helodermatid lizards (one Mexican beaded lizard and two Gila
      monsters) and identified as AdVs based on electron microscopy and PCR and
      sequencing using cell culture supernatant. This is the first report of the
      successful isolation of a lizard AdV.

PMID- 18824314
TI  - Non-invasive ventilation of the preterm infant.
AB  - Non-invasive ventilation (NIV) is increasingly being used in preterm infants with
      the purpose of reducing the risk of adverse pulmonary outcome associated with
      invasive mechanical ventilation. This review analyzes the evidence from
      physiologic and clinical studies on the use of NIV in the preterm infant.
      Physiologic data indicate advantages of NIV with regard to ventilation, gas
      exchange, breathing effort and thoraco-abdominal distortion. Data from clinical
      trials have consistently shown facilitation of weaning from mechanical
      ventilation and potential benefits in infants with RDS and apnoea. Long term
      improvements in respiratory outcome have also been reported but need to be
      confirmed in larger trials.

PMID- 18824313
TI  - Similar cefoxitin-resistance plasmids circulating in Escherichia coli from human
      and animal sources.
AB  - The aim of this study was to determine the molecular epidemiology of cefoxitin
      resistance Escherichia coli identified in cattle entering feedlots and determine
      if there were any similarities to E. coli causing human infections in Canadian
      hospitals. A total of 51 E. coli were isolated from a total of 2483 cattle
      entering four feedlots in southern Alberta, Canada. DNA fingerprinting using
      pulsed-field gel electrophoresis revealed thirty-two unique patterns with two
      major clusters observed comprised of Cluster A (11 strains) and Cluster B (7
      strains). PCR and sequence analysis revealed 38 isolates (74.5%) harboured
      bla(CMY-2), whereas the remainder were found to contain mutations in the promoter
      region of the chromosomal ampC gene, which has been previously associated with
      cefoxitin resistance. No resistance to nalidixic acid, ciprofloxacin, or amikacin
      was observed in the clinical isolates. bla(CMY-2) harbouring plasmids were
      transferred to E. coli DH10B. All of the plasmids carrying bla(CMY-2) contained
      the A/C replicon and also harboured other resistance genes. Plasmid
      fingerprinting using BglII revealed 17 unique patterns with all but one
      clustering within 70% similarity. Comparison of the plasmid fingerprints to those
      isolated from human clinically significant E. coli in Canada during a similar
      time period [Mulvey, M.R., Bryce, E., Boyd, D.A., Ofner-Agostini, M., Land, A.M.,
      Simor, A.E, Paton, S., 2005. The Canadian Hospital Epidemiology Committee, and
      The Canadian Nosocomial Infection Surveillance Program, Health Canada. Molecular
      characterization of cefoxitin resistant Escherichia coli from Canadian hospitals.
      Antimicrob. Agents Chemother. 49, 358-365] revealed four strains that harboured
      bla(CMY-2) A/C replicon type plasmid with fingerprint similarities of greater
      than 90% to the ones identified in E. coli from the cattle in this study. These
      findings highlight the potential linkage of multidrug resistant organisms in food
      producing animals and human infections in Canadian hospitals. The plasmids
      conferred resistance to multiple antibiotics which could limit options for the
      treatment of infections caused by these strains.

PMID- 18824315
TI  - Direct contact between boar spermatozoa and porcine oviductal epithelial cell
      (OEC) cultures is needed for optimal sperm survival in vitro.
AB  - Oviductal epithelial cell (OEC) co-culture prolongs sperm viability and motility
      in vitro in a number of species including humans and horses. This study has
      sought to determine the effects of homologous OEC co-culture on boar sperm
      function. To determine whether the effects on spermatozoa were specifically
      caused by co-culture with or by OEC secretions, or by both factors together, a
      number of co-culture and cell-conditioned medium (CM) experiments were conducted.
      Firstly, Percoll-washed spermatozoa were co-cultured with OECs and pig kidney
      epithelial (LLC-PK1) cells, and in medium without cells. Secondly, Percoll-washed
      spermatozoa were incubated with CM derived from both OECs and LLC-PK1 cells and
      in unconditioned medium. A number of sperm function parameters were assessed
      after 5, 30, 60, 90, 120, and 180 min, and 24h of co-culturing or incubation with
      CM. Of all the sperm function parameters investigated, the percentage (%)
      viability data yielded the most interesting results. OECs (mean+/-S.E.M.; 31.2+/
      1.10) were better than LLC-PK1 cells (24.3+/-0.93) at prolonging the viability of
      unbound spermatozoa after 24h of co-culturing (P<0.05). Also after 24h, the
      viability of spermatozoa bound to the OECs (77.6+/-1.83) was significantly higher
      than in the case of the LLC-PK1 cells (53.5+/-1.43; P<0.001). Other sperm
      function parameters, e.g., capacitation and motility, were also influenced by OEC
      co-culturing and incubation with CM, although to a lesser degree. In conclusion,
      porcine homologous OEC co-culture and CM incubation specifically affect sperm
      function. However, we propose that it is OEC co-culturing, rather than OEC-CM,
      that has the greater influence.

PMID- 18824316
TI  - The effects of PG600 and boar exposure on oestrus detection and potential litter
      size following mating at either the induced (pubertal) or second oestrus.
AB  - Within gilt pools, incidences of delayed puberty attainment, failure to exhibit
      regular oestrous cycles and low first litter size are often high. Boar exposure
      is an effective method of accelerating puberty; however, the timing of gilt
      response can vary greatly. Although, PG600 (400 IU of PMSG and 200 IU of hCG;
      Intervet) can induce a rapid and synchronous ovulatory response, thus providing
      an alternative to boar contact, the quality of the response is often variable.
      This study compared the effect of PG600, either alone (NBC) or in conjunction
      with boar exposure (BC), on puberty attainment and maintenance of oestrous
      cyclicity. The effects of first mating these gilts at the hormonally induced
      (pubertal) or second oestrus on ovulation rate and early embryo survival were
      also studied. Eighty Large White cross terminal (Duroc) line gilts were used in
      this study. The study was conducted in two blocks, with 10 gilts allocated to
      each of the four treatments in each block. Gilts were artificially inseminated at
      the allocated oestrus, with the reproductive tracts collected at 26.5+/-0.29 days
      after first mating (mean+/-S.E.M.), and the number of corpora lutea and viable
      embryos recorded. Mean days-to-puberty was significantly reduced (P<0.05) when
      gilts received both PG600 and boar exposure as opposed to PG600 alone (5.7+/-0.15
      versus 6.9+/-0.37 days; P<0.01). The proportion of gilts exhibiting an ovulatory
      response to PG600 was similar for the BC and NBC treatment groups (0.88 and
      0.84); however, the proportion of gilts exhibiting visible signs of oestrus in
      response to PG600 was significantly higher for the BC compared to the NBC
      treatment groups (0.81 versus 0.49; P<0.05). Boar contact resulted in a
      numerical, but not significant, increase in the proportion of gilts exhibited a
      second oestrus (1.00 versus 0.76). There was no significant effect of boar
      contact on ovulation rate, embryo number or survival. Although ovulation rate was
      unaffected by oestrus at mating, embryo number was significantly increased
      (P<0.05) following mating at the second compared to the first oestrus (11.2+/
      0.96 versus 7.8+/-1.17). In conclusion, the current data indicate that the timing
      of puberty attainment and oestrus detection are significantly improved when PG600
      treated gilts receive full boar contact. Further, it is evident that mating gilts
      at their second as opposed to the hormonally induced oestrus significantly
      increases embryo number at day 26 post-mating.

PMID- 18824317
TI  - Examining the effects of paper type, pen type, writing pressure and angle of
      intersection on white and dark dominance in ESDA impressions of sequenced strokes
      -an application of the likelihood ratio.
AB  - Questioned document casework can occasionally involve the sequencing of
      impressions. Although some conclusions can be drawn from looking at ESDA traces
      of intersections there is currently no way of assessing the strength of the
      observations made in any given case. Using a range of paper and pen types this
      work examines points of intersection and evaluates the results statistically in
      order judge the value of the results obtained.

PMID- 18824318
TI  - Doppler waveforms of the hepatic veins in children with diffuse fatty
      infiltration of the liver.
AB  - OBJECTIVE: The aim of this study was to investigate the effect of fatty
      infiltration of the liver (FIL) on the Doppler waveform pattern in the hepatic
      veins of obese children. METHODS: In this prospective study, 59 patients with
      diffuse FIL and 45 normal healthy children who served as control group underwent
      hepatic vein B-mod and duplex Doppler sonography. The Doppler sonography spectrum
      of the right hepatic vein was classified into three groups: triphasic waveform,
      biphasic waveform, and monophasic or flat waveform. RESULTS: There was a
      statistically significant difference in the phasicity of hepatic venous flow
      between patients and control subjects (p<0.001). The Doppler flow pattern in the
      right hepatic vein was triphasic in 28 (47.5%), biphasic in 28 (47.5%), and
      monophasic in 3 (5%) children with fatty liver, while it was triphasic in 43
      (95.6%) and biphasic in 2 (4.4%) control subjects. There was an inverse
      correlation between the sonographic grade of fatty infiltration of the liver and
      the phasicity of hepatic venous flow (r=-0.479, p<0.001). CONCLUSIONS: Abnormal
      right hepatic vein Doppler waveform, biphasic as well as monophasic, can be seen
      in healthy obese children with diffuse FIL.

PMID- 18824319
TI  - Health related quality of life after radical cystectomy: comparison of ileal
      conduit to continent orthotopic neobladder.
AB  - AIMS: To compare health related quality of life (HRQOL) between patients with two
      different types of urinary diversion, ileal conduit and orthotopic neobladder,
      and between them and an age-matched population of healthy subjects. MATERIALS AND
      METHODS: Eighty eight patients treated with radical cystectomy for bladder cancer
      at our institutions between 2002 and 2007 were contacted for this survey. All of
      them had a follow-up of more than 12 months after surgery and were recurrence
      free. The SF-36 questionnaire was provided to each patient during a follow-up
      visit at outpatient clinics. Overall, 79 patients (90%) returned the
      questionnaire and were included in this analysis. They were divided into two
      groups: group 1 comprised 44 patients with an ileal conduit diversion, and group
      2 included 35 patients with a neobladder. As a control, normative values of an
      age-matched healthy Italian population were considered. RESULTS: No significant
      difference was found in scale scores between the neobladder and ileal conduit
      groups. Scale scores for role-physical functioning, social functioning and role
      emotional functioning in both the neobladder and ileal conduit groups were
      significantly below the Italian population norm. Patients with a neobladder 65
      years old or older (n=18) had significantly lower scores for role-physical
      functioning and role-emotional functioning than those younger than 65 years
      (n=17; p<0.05). CONCLUSION: Few differences between ileal conduit and orthotopic
      bladder substitution have been detected. Thus, the assumption that continent
      reconstruction provides better HRQOL than ileal conduit diversion cannot be
      supported. Patient education and active participation in treatment decisions seem
      to be the key to postoperative satisfaction.

PMID- 18824320
TI  - [Brain placement of a double balloon catheter after extensive craniofacial
      trauma].
AB  - An extensive craniofacial trauma is often associated with skull basal fractures
      and severe epistaxis. Such event requires nasal packing, using balloon systems or
      even arterial embolization or ligation. However, the use of balloon systems may
      result in an intracranial position. We report here such a case in an 18-year-old
      man suffering from a severe nasal bleeding.

PMID- 18824321
TI  - [Is the person of trust a reliable witness in case of organ removal from a
      deceased person for donation purposes?].
AB  - OBJECTIVES: All adults (people over the age of 18) can assign a person of trust
      and this person can be a parent, a partner or the treating doctor. Following the
      introduction of the 4(th) March 2002 law, this third party is now within the
      doctor-patient relationship. The aim of this study is to find out who is
      appointed as a person of trust by patients notably concerning the level of
      education or medical knowledge of these people. We have equally put the person of
      trust to the test within the realms that they would be questioned regarding organ
      donation from the deceased. PATIENTS AND METHODS: The included subjects were
      adults admitted to hospital for surgical procedures or medical biopsies that were
      not deemed life threatening. The data collection was done by doctors from the
      legal medicine department at the university hospital of Amiens over a period of
      18 months. With the permission of the patient and his or her person of trust, a
      one-to-one discussion was held. Statistical analysis took place focusing on all
      the variables together and is shown by comparing the patient group versus the
      person of trust group. The significance threshold returned was 0.05. RESULTS: A
      total of 125 patients-persons of trust couples were interviewed. The patients and
      their person of trust were not different in terms of age, social status,
      occupational groups and education. However, a person of trust is more often a
      woman (64%) against 50% of patients. A person of trust more often lives as a
      couple than the patients. Concerning organ donation, over half of the people
      questioned were for donation but only a third of patients had already discussed
      the subject with their person of trust. The persons of trust bring in 40% of
      cases a response that is not concordant in the position of the patient.
      DISCUSSION: The creation of a person of trust due to the law of 4(th) March 2002
      brings about the opportunity for the patient to take on an approach, with the
      doctors, of having somebody that can advise them. Yet in this study, there is no
      significant evidence of a difference between the level of education of patients
      and that of their person of trust, or a difference in the distribution of the
      socio-professional categories, or specific choices for the GP. The person of
      trust can be used to wait on behalf of the patient whilst he or she is not able
      to do so. Even if the patient feels that the person of trust has come first over
      other close friends or relatives, the persons of trust assume this role with
      difficulty. Since its creation, the person of trust was presented as a response
      to social demand; however, it seems that patients are not sufficiently informed
      when it comes to the possibilities that are on offer to them.

PMID- 18824322
TI  - [Fatal air embolism during open eye surgery].
AB  - Gas embolism is well known for a specific subset of surgical interventions.
      Prevention and early detection are the main objectives of the anesthetic and
      surgical team. However, it may exceptionally occur during eye surgery with
      dramatic outcomes. We report the case of a 51-year-old man, ASA physical status
      1, who presented a cardiac arrest during an open eye surgery for the extraction
      of a foreign body with intraocular air injection. Multiple organ failure has not
      been improved by hyperbaric oxygen therapy and the outcome was fatal.

PMID- 18824323
TI  - Decreased immune response in alexithymic women: a cross-sectional study.
AB  - It has been reported in a few studies that alexithymia is associated with
      impaired immune response but results are still contradictory. The present study
      investigates whether alexithymia is associated with lower cell-mediated (Th-1)
      immune response. Fifty-one healthy 18-27-year-old women were selected from
      healthy subjects on the basis of high or low cut-off scores on the 20-item
      Toronto Alexithymia Scale (TAS-20). They were evaluated using standardized
      psychiatric rating scales notably the Hospital Anxiety Depressive Scale (HAD) and
      the Mini Neuropsychiatric Interview (MINI). None of the subjects were suffering
      from psychiatric disorders. Twenty-seven were classified as alexithymics and 24
      as non-alexithymics according to the TAS-20. Blood was drawn for lymphocyte
      subset counts (CD4, CD8), in vitro production of interleukin 1 (IL-1beta), IL-2,
      IL-4, and IL-10 by phytohaemagglutinin stimulated peripheral lymphocytes, and
      cortisol. Women with alexithymia exhibited decreased interleukin 1beta, IL-2 and
      IL-4 production with reduced ratios of Th1/Th2 (IL-2/IL-10) and of CD4/CD8, as
      well as reduced CD4 percentages. IL-2 and IL-4 production remained significantly
      diminished in the alexithymic group, even after adjusting for between-group
      differences in anxiety and depression levels on the HAD. This study further
      demonstrates that alexithymic women have altered immune function, with a
      predominance of depressed cell-mediated immunity and a skewed Th1/Th2 ratio
      towards Th2 response.

PMID- 18824324
TI  - [Is coloscopy required for all streptococcic bacteremias?].

PMID- 18824325
TI  - Re: "a novel technique for the removal of well-fixed cementless, large-diameter
      metal-on-metal acetabular components" by Olyslaegers et al.

PMID- 18824326
TI  - Thrombosis of popliteal artery pseudoaneurysm by deployment of angioplasty
      balloon after total knee arthroplasty.
AB  - Vascular complications after total knee arthroplasty are rare, with incidence
      ranging between 0.03% and 0.2%. We describe a case of a popliteal artery false
      aneurysm after total knee arthroplasty successfully treated by deployment of an
      angioplasty balloon across the aneurysm neck resulting in thrombosis.

PMID- 18824327
TI  - A response to the article of Lau et al. "A systematic review on MEG and its use
      in the presurgical evaluation of localization related epilepsy", Epilepsy
      Research 2008;79(May (2-3)):97-104.

PMID- 18824328
TI  - Daily activities, cognition and community functioning in persons with
      schizophrenia.
AB  - OBJECTIVE: This cross-sectional study explored the relationships between daily
      activity performance, attention, memory, executive functions and community
      functioning in people with schizophrenia. More specifically, this study attempted
      to verify the hypothesis that functional limitations in the performance of daily
      activities negatively affect community functioning in people with schizophrenia.
      METHODS: Eighty-two individuals with schizophrenia living in the community were
      recruited for the study. The Perceive, Recall, Plan and Perform (PRPP) System of
      Task Analysis was used to assess participants' functional capacity during a meal
      preparation task. Visuo-spatial associative memory, spatial working memory,
      planning, visuo-motor coordination, and selective attention were evaluated as
      well. Community functioning was assessed with the Independent Living Skills
      Survey (ILSS) and the Multnomah Community Ability Scale (MCAS). RESULTS:
      Correlations revealed significant associations between functional capacity and
      visuo-spatial associative learning, spatial working memory, planning and negative
      symptoms. Planning skills during meal preparation were found to be associated
      with MCAS. After regression analyses, only visuo-spatial memory, negative
      symptoms, education and familiarity with meal preparation explained variation in
      functional capacity. CONCLUSIONS: The findings of the current study suggest that
      visuo-spatial associative learning, negative symptoms, education and familiarity
      with task are among the important factors for functional capacity. Planning
      skills necessary for efficient task performance were also found to be those most
      determinant for community functioning. Rehabilitation interventions should
      consider these underlying strength and deficits when developing strategies to
      help people with schizophrenia build functional skills essential for community
      living.

PMID- 18824329
TI  - Dysregulated genes of extrinsic type of atopic dermatitis: 34K microarray and
      interactomic analyses.

PMID- 18824330
TI  - Stability of antibacterial agents in MGIT Para TB Medium.

PMID- 18824332
TI  - Study of molecular dynamics and cross relaxation in tetramethylammonium
      hexafluorophosphate (CH(3))(4)NPF(6) by (1)H and (19)F NMR.
AB  - (CH(3))(4)NPF(6) is studied by NMR measurements to understand the internal
      motions and cross relaxation mechanism between the heterogeneous nuclei. The spin
      lattice relaxation times (T(1)) are measured for (1)H and (19)F nuclei, at three
      (11.4, 16.1 and 21.34 MHz) Larmor frequencies in the temperature range 350-50K
      and (1)H NMR second moment measurements at 7 MHz in the temperature range 300
      100K employing home made pulsed and wide-line NMR spectrometers. (1)H NMR results
      are attributed to the simultaneous reorientations of both methyl and
      tetramethylammonium groups and motional parameters are evaluated. (19)F NMR
      results are attributed to cross relaxation between proton and fluorine and
      motional parameters for the PF(6) group reorientation are evaluated.

PMID- 18824331
TI  - Improvement of aggressive behavior and quality of life impairment following S
      adenosyl-methionine (SAM-e) augmentation in schizophrenia.
AB  - S-adenosyl-methionine (SAM-e), functions as a primary methyl group donor for
      several metabolic compounds. Since SAM-e is involved in several metabolic
      processes, its administration may have a role in the amelioration of several
      disorders. In addition, SAM-e increases catechol-O-methyltransferase (COMT)
      enzyme activity, which may ameliorate aggressive symptoms in certain patients. We
      have therefore investigated the efficacy of SAM-e in managing schizophrenia
      symptomatology in patients with the low activity COMT polymorphism. Eighteen
      patients with chronic schizophrenia were randomly assigned to receive either SAM
      e (800 mg) or placebo for 8 weeks in double-blind fashion. Results indicated some
      reduction in aggressive behavior and improved quality of life following SAM-e
      administration. Female patients showed improvement of depressive symptoms.
      Clinical improvement did not correlate with serum SAM-e levels. Two patients
      receiving SAM-e exhibited some exacerbation of irritability. This preliminary
      pilot short-term study cautiously supports SAM-e as an adjunct in management of
      aggressive behavior and quality of life impairment in schizophrenia.

PMID- 18824333
TI  - Polyethyleneglycol-pepsin interaction and its relationship with protein
      partitioning in aqueous two-phase systems.
AB  - The interaction between the acidic protein, pepsin, and the non-charged
      polyethyleneglycol polymer was studied by dynamic light scattering, fluorescence
      spectroscopy and measurements of the protein thermal stability at neutral pH.
      Polyethyleneglycol of average molecular mass 1450 showed a higher interaction
      capacity with the protein than polyethyleneglycol of average molecular mass 8000.
      Polyethyleneglycol of average molecular mass 1450 showed a molecular mechanism
      where the interpolymer interaction led to the complex formation. This fact can be
      explained taking into account that the extended form on this polymer molecule
      favours the interaction with the protein, which is highly dependent of the
      polymer total concentration. Polyethyleneglycol of average molecular mass 8000
      showed a cooperative interaction between the polymer and protein molecules which
      was independent of the PEG concentration.

PMID- 18824334
TI  - [One year of activity in a pediatric rheumatology unit in the Ibn-Rochd
      University Children's Hospital of Casablanca, Morocco].

PMID- 18824335
TI  - Using model checking for critiquing based on clinical guidelines.
AB  - OBJECTIVE: Medical critiquing systems compare clinical actions performed by a
      physician with a predefined set of actions. In order to provide useful feedback,
      an important task is to find differences between the actual actions and a set of
      'ideal' actions as described by a clinical guideline. In case differences exist,
      the critiquing system provides insight into the extent to which they are
      compatible. METHODS AND MATERIAL: We propose a computational method for such
      critiquing, where the ideal actions are given by a formal model of a clinical
      guideline, and where the actual actions are derived from real world patient data.
      We employ model checking to investigate whether a part of the actual treatment is
      consistent with the guideline. RESULTS: We show how critiquing can be cast in
      terms of temporal logic, and what can be achieved by using model checking.
      Furthermore, a method is introduced for off-line computing relevant information
      which can be exploited during critiquing. The method has been applied to a
      clinical guideline of breast cancer in conjunction with breast cancer patient
      data.

PMID- 18824336
TI  - The importance of the immune system in reovirus therapy.

PMID- 18824337
TI  - Discordance between receptor status in primary and metastatic breast cancer: an
      exploratory study of bone and bone marrow biopsies.
AB  - AIMS: The treatment of bone metastases in breast cancer is traditionally based
      upon the receptor status of the primary tumour. However, retrospective studies
      have shown significant discordance in receptor expression between primary and
      metastatic tumours. Therefore, the aim of this study was to prospectively assess
      the incidence of discordant receptor status in primary and metastatic disease and
      evaluate the role of bone marrow biopsies for the reassessment of receptor
      status. MATERIALS AND METHODS: Nine patients with known bone metastases were
      assessed with both a radiologically guided bone biopsy and a bone marrow aspirate
      and trephine. The oestrogen receptor and progesterone receptor status of these
      samples was assessed and compared with the primary breast cancer. Bone and bone
      marrow samples were also evaluated for HER2/neu status and compared with the
      status of the primary tumour if available. RESULTS: Tumour cells were found in
      six of the nine bone metastasis specimens and five of the nine bone marrow
      samples. A discordance rate for the oestrogen receptor was seen in five of nine
      patients (56%) and for the progesterone receptor in four patients (44%). There
      seemed to be a correlation between bone and bone marrow biopsies. CONCLUSION: The
      receptor discordance rate in this study was similar to previous retrospective
      studies. It seems that bone marrow biopsy may be a simple, safe and well
      tolerated way to obtain tissue to reassess the receptor status of metastatic
      breast cancer.

PMID- 18824338
TI  - A comparative study of the therapeutic effects of the Zataria multiflora vaginal
      cream and metronidazole vaginal gel on bacterial vaginosis.
AB  - Bacterial vaginosis (BV) is one of most prevalent complications among
      reproductive-aged women. Metromidazole prescription, which is considered as the
      first-line treatment of BV, is usually followed by a few side effects. Besides,
      there is a growing tendency toward herbal medicines for the treatment of
      vaginitis. Antibacterial and antifungal effects of Zataria multiflora (Z.
      multiflora) have been demonstrated in vitro and in vivo. This study aimed to
      compare the therapeutic effects of the Z. multiflora vaginal cream and
      metronidazole vaginal gel on bacterial vaginosis. This was a randomized clinical
      trial on 90 married women aged 18-40 affected by BV who attended for treatment to
      the gynecology clinic of Shabih-Khani Hospital. They randomly divided to two
      groups of 45 participants. Diagnostic criteria were Amsel's criteria and Gram
      stain. Z. multiflora vaginal cream or metronidazole vaginal gel for five-night
      usage were prescribed to each group, and after 2-7 days therapeutic effects on
      participants' complications and their Amsel criteria were assessed. Data analysis
      was performed by McNemar and Fisher exact tests. Patients' complication and their
      Amsel's criteria were significantly decreased after treatment with Z. multiflora
      or metronidazole (p<0.05). Relative risk for unresponsiveness to treatment with
      Z. multiflora, to unresponsiveness to metronidazole was 1.5, which was not
      significant. Therapeutic effects of Z. multiflora vaginal cream are similar to
      metronidazole vaginal gel on BV. Therefore it could be an appropriate choice to
      BV treatment for those interested in herbal medicines or those affected by side
      effects of metronidazole.

PMID- 18824339
TI  - Inhaled linalool-induced sedation in mice.
AB  - Linalool is a monoterpene often found as a major component of essential oils
      obtained from aromatic plant species, many of which are used in traditional
      medical systems as hypno-sedatives. Psychopharmacological evaluations of linalool
      (i.p. and i.c.v.) revealed marked sedative and anticonvulsant central effects in
      various mouse models. Considering this profile and alleged effects of inhaled
      lavender essential oil, the purpose of this study was to examine the sedative
      effects of inhaled linalool in mice. Mice were placed in an inhalation chamber
      during 60 min, in an atmosphere saturated with 1% or 3% linalool. Immediately
      after inhalation, animals were evaluated regarding locomotion, barbiturate
      induced sleeping time, body temperature and motor coordination (rota-rod test).
      The 1% and 3% linalool increased (p<0.01) pentobarbital sleeping time and reduced
      (p<0.01) body temperature. The 3% linalool decreased (p<0.01) locomotion. Motor
      coordination was not affected. Hence, linalool inhaled for 1h seems to induce
      sedation without significant impairment in motor abilities, a side effect shared
      by most psycholeptic drugs.

PMID- 18824340
TI  - Recombinant tissue plasminogen activator in the treatment of pleural infections
      in adults.
AB  - BACKGROUND: Intrapleural recombinant tissue plasminogen activator (r-TPA) has
      been successfully evaluated in pediatric patients with complicated parapneumonic
      pleural effusion (CPE) and pleural empyema (PE). Yet, there is no data concerning
      r-TPA in adults with CPE/PE. The aim of our study was to investigate the efficacy
      and complications of r-TPA in adult patients with CPE/PE. METHODS: Twenty
      consecutive patients (mean age 50+/-18.9 years) with pleural infection (14 CPE
      and 6 PE) were included. Chest tube was inserted under guidance of chest
      ultrasound and/or computed tomography. After failure of pleural fluid drainage,
      25mg of r-TPA was administered intrapleurally in a single daily dose. The
      evaluation was made according to imaging and clinical status. RESULTS: The mean
      volume of fluid increased significantly after r-TPA administration (p<0.0001).
      White blood cells count (WBC) and C-reactive protein (CRP) were significantly
      improved after r-TPA instillations (both p<0.0001). Significant clinical and
      imaging improvement was noted in all but one patient after r-TPA administration
      (overall p<0.0001). Complications observed were mild: pain in 4 (25%) and local
      bleeding in 3 (15%) patients. The median number of r-TPA instillations was 3
      (range 2-5). CONCLUSION: Intrapleural instillation of r-TPA at a dose of 25 mg is
      a well-tolerated and effective treatment in 95% of our adult patients with
      CPE/PE.

PMID- 18824341
TI  - Lycopene enrichment of cultured airway epithelial cells decreases the
      inflammation induced by rhinovirus infection and lipopolysaccharide.
AB  - Rhinovirus infection results in increased release of inflammatory mediators from
      airway epithelial cells in asthma. As an antioxidant, lycopene offers protection
      from adverse effects of inflammation. The aim of this study was to find an
      appropriate method of lycopene enrichment of airway epithelial cells and to
      determine the effects of lycopene enrichment on the inflammatory response of
      cells infected by rhinovirus or exposed to lipopolysaccharide. Lycopene
      enrichment of airway epithelial cells using solubilisation in tetrahydrofuran
      versus incorporation in liposomes was compared. After determining that
      solubilisation of lycopene in tetrahydrofuran was the most suitable method of
      lycopene supplementation, airway epithelial cells (Calu-3) were incubated with
      lycopene (dissolved in tetrahydrofuran) for 24 h, followed by rhinovirus
      infection or lipopolysaccharide exposure for 48 h. The release of interleukin-6,
      interleukin-8 and interferon-gamma induced protein-10 (IP-10) and their messenger
      RNA levels were measured using enzyme linked immunosorbent assay and reverse
      transcription polymerase chain reaction, respectively. Viral replication was
      measured by tissue culture infective dose of 50% assay. Lycopene concentration of
      cells and media were analysed using high-performance liquid chromatography.
      Preincubation of airway epithelial cells with lycopene (dissolved in
      tetrahydrofuran) delivered lycopene into the cells and resulted in a 24%
      reduction in interleukin-6 after rhinovirus-1B infection, 31% reduction in IP-10
      after rhinovirus-43 infection and 85% reduction in rhinovirus-1B replication.
      Lycopene also decreased the release of IL-6 and IP-10 following exposure to
      lipopolysaccharide. We conclude that lycopene has a potential role in suppressing
      rhinovirus induced airway inflammation.

PMID- 18824342
TI  - Specific accumulation of gamma- and delta-tocotrienols in tumor and their
      antitumor effect in vivo.
AB  - In contrast to extensive studies on tocopherols, very little is understood about
      tocotrienols (T3). We evaluated the antitumor activities of gamma-T3 and delta-T3
      in murine hepatoma MH134 cells in vitro and in vivo. We found that delta-T3
      inhibited the growth of MH134 cells more strongly than gamma-T3 by inducing
      apoptosis. In C3H/HeN mice implanted with MH134, it was found that gamma-T3 and
      delta-T3 feeding significantly delayed tumor growth. On the other hand, both T3
      had no significant effect on body weight, normal-tissue weight and immunoglobulin
      levels. Intriguingly, we found that T3 was detected in tumor, but not in normal
      tissues. These results, to our knowledge, are the first demonstration of specific
      accumulation of gamma-T3 and delta-T3 in tumors and suggest that T3 accumulation
      is critical for the antitumor activities of T3.

PMID- 18824343
TI  - Experimental models and mechanisms underlying the protective effects of n-3
      polyunsaturated fatty acids in Alzheimer's disease.
AB  - Dementia such as Alzheimer's disease (AD) is a growing health problem in aging
      populations in many countries around the world. Currently, there is no cure for
      AD; consequently, alternative therapies are urgently needed. Recent studies
      suggest that nutritional intervention may have therapeutic benefits for AD.
      Specifically, an increased intake of n-3 polyunsaturated fatty acids (PUFA) from
      fish and marine oils may lower AD risk. This review will summarize the current
      body of knowledge regarding the association between n-3 PUFA and AD, including
      human studies and experimental models, and potential mechanisms of action.

PMID- 18824344
TI  - Extracts of Lindera obtusiloba induce antifibrotic effects in hepatic stellate
      cells via suppression of a TGF-beta-mediated profibrotic gene expression pattern.
AB  - Liver fibrosis is characterized by high expression of the key profibrogenic
      cytokine transforming growth factor (TGF)-beta and the natural tissue inhibitor
      of metalloproteinases (TIMP)-1, leading to substantial accumulation of
      extracellular matrix. Liver fibrosis originates from various chronic liver
      diseases, such as chronic viral hepatitis that, to date, cannot be treated
      sufficiently. Thus, novel therapeutics, for example, those derived from Oriental
      medicine, have gained growing attention. In Korea, extracts prepared from Lindera
      obtusiloba are used for centuries for treatment of inflammation, improvement of
      blood circulation and prevention of liver damage, but experimental evidence of
      their efficacy is lacking. We studied direct antifibrotic effects in activated
      hepatic stellate cells (HSCs), the main target cell in the fibrotic liver. L.
      obtusiloba extract (135 mug/ml) reduced the de novo DNA synthesis of activated
      rat and human HSCs by about 90%, which was not accompanied by cytotoxicity of
      HSC, primary hepatocytes and HepG2 cells, pointing to induction of cellular
      quiescence. As determined by quantitative polymerase chain reaction, simultaneous
      treatment of HSCs with TGF-beta and L. obtusiloba extract resulted in reduction
      of TIMP-1 expression to baseline level, disruption of the autocrine loop of TGF
      beta autoinduction and increased expression of fibrolytic matrix
      metalloproteinase (MMP)-3. In addition, L. obtusiloba reduced gelatinolytic
      activity of HSC by interfering with profibrogenic MMP-2 activity. Since L.
      obtusiloba extract prevented intracellular oxidative stress experimentally
      induced by tert-butylhydroperoxide, we concluded that the direct antifibrotic
      effect of L. obtusiloba extract might be mediated by antioxidant activity. Thus,
      L. obtusiloba, traditionally used in Oriental medicine, may complement treatment
      of chronic liver disease.

PMID- 18824345
TI  - Isoliquiritigenin inhibits migration and invasion of prostate cancer cells:
      possible mediation by decreased JNK/AP-1 signaling.
AB  - Isoliquiritigenin (ISL, 4,2',4'-trihydroxychalcone), which is found in licorice,
      shallot and bean sprouts, is a potent antioxidant with anti-inflammatory and anti
      carcinogenic effects. The purpose of this study was to investigate the effects of
      ISL treatment on the migration, invasion and adhesion characteristics of DU145
      human prostate cancer cells. DU145 cells were cultured in the presence of 0-20
      micromol/L ISL with or without 10 microg/L epidermal growth factor (EGF). ISL
      inhibited basal and EGF-induced cell migration, invasion and adhesion dose
      dependently. ISL decreased EGF-induced secretion of urokinase-type plasminogen
      activator (uPA), matrix metalloproteinase (MMP)-9, tissue inhibitor of
      metalloproteinase-1 (TIMP-1), and vascular endothelial growth factor (VEGF), but
      increased TIMP-2 secretion in a concentration-dependent manner. In addition, ISL
      decreased the protein levels of integrin-alpha2, intercellular adhesion molecule
      (ICAM) and vascular cell adhesion molecule (VCAM), and mRNA levels of uPA, MMP-9,
      VEGF, ICAM and integrin-alpha2. Furthermore, basal and EGF-induced activator
      protein (AP)-1 binding activity and phosphorylation of Jun N-terminal kinase
      (JNK), c-Jun and Akt were decreased after ISL treatment. However, phosphorylation
      of extracellular signal-regulated kinase (ERK)1/2 and p38 mitogen-activated
      protein kinase was not altered. The JNK inhibitor SP600125 inhibited basal and
      EGF-induced secretion of uPA, VEGF, MMP-9 and TIMP-1, as well as AP-1 DNA binding
      activity and cell migration. These results provide evidence for the role of ISL
      as a potent antimetastatic agent, which can markedly inhibit the metastatic and
      invasive capacity of prostate cancer cells. The inhibition of JNK/AP-1 signaling
      may be one of the mechanisms by which ISL inhibits cancer cell invasion and
      migration.

PMID- 18824346
TI  - Status and prospects of pay-as-you-throw in Europe - a review of pilot research
      and implementation studies.
AB  - Over the past 20 years, significant advances have been made in developing
      efficient schemes to charge households for their actual waste generation. Viable
      fee models and technical solutions which are applicable to different environments
      and provide waste generators with individual incentives for waste diversion
      efforts have increased the recognition of pay-as-you-throw (PAYT) as an effective
      instrument for recycling-oriented waste management and financing. On this basis,
      PAYT has become a practical reality in an increasing number of countries in
      Europe. Even countries with traditional reservations for direct charging have
      started to make consideration of PAYT in the revision of their national policy
      programmes. A situational analysis performed at the European level showed that
      detailed insights regarding the concrete reactions, red flags and wider benefits
      inherent to such scheme may still have to be further dispersed in order to
      overcome the caveats on PAYT and eventually adopt the approach on a larger scale.
      Claims that the results of PAYT applications are only local in meaning can be
      disproved as many of the developments bear universal character and can be
      verified even for larger territories using such schemes in different ways.
      Including results from an international research co-operation and comparative
      studies conducted in Germany, this article examines the state-of-the-art of PAYT
      and shades light onto some of the generally observed implications of its
      implementation. In conclusion, an outlook on the further potentials and
      propagation of this scheme is given.

PMID- 18824347
TI  - Dynamic measurement of the surface stress induced by the attachment and growth of
      cells on Au electrode with a quartz crystal microbalance.
AB  - The processes of adhesion, spreading and proliferation of human mammary cancer
      cells MCF-7 on two Au electrodes with different surface roughness (R(f) and
      R(f)=3.2 or 1.1) were monitored and clearly identified with the quartz crystal
      microbalance (QCM) technique. Analyses of the QCM responses on the resonant
      frequency shifts (Deltaf(0)) vs. the motional resistance changes (DeltaR(1))
      revealed a significant surface-stress effect in the involved courses, in addition
      to a viscodensity effect and a relatively small mass effect (especially at the
      smooth electrode). Experiments of fluorescence microscopy, cyclic voltammetry and
      electrochemical impedance spectroscopy were conducted to investigate the cell
      population on the electrode vs. the electrode-surface roughness. Simplified
      equations are deduced to quantitatively evaluate the surface stress, and a novel
      QCM method for dynamically measuring the surface stress on an electrode in cell
      culture course is thus described. It was found that the smoother surface
      (R(f)=1.1) gave a higher surface stress during cell attachment and less cell
      population on it than the rougher surface (R(f)=3.2). In addition, real-time QCM
      monitoring showed on the same electrode the surface stress induced by hepatic
      normal cells being notably higher than that caused by hepatic cancer cells at
      cell-attachment stage, suggesting that the surface-stress measurement can exhibit
      the difference of adhesion-performance between the healthy and ill-behaved cells.

PMID- 18824348
TI  - Cloning and expression of an antifungal chitinase gene of a novel Bacillus
      subtilis isolate from Taiwan potato field.
AB  - A chitinase producing Bacillus subtilis CHU26 was isolated from Taiwan potato
      field. This strain exhibited a strong extra-cellular chitinase activity on the
      colloidal chitin containing agar plate, and showed a potential inhibit activity
      against phytopathogen, Rhizoctonia solani. The gene encoding chitinase (chi18)
      was cloned from the constructed B. subtilis CHU26 genomic DNA library. The chi18
      consisted of an open reading frame of 1791 nucleotides and encodes 595 amino
      acids with a deduced molecular weight of 64kDa, next to a promoter region
      containing a 9 base pair direct repeat sequence (ATTGATGAA). The deduced amino
      acid sequence of the chitinase from Bacillus subtilis CHU26 exhibits 62% and 81%
      similarity to those from B. circulans WL-12 and B. licheniformis, respectively.
      Subcloned chi18 into vector pGEM3Z and pYEP352 to construct recombinant plasmid
      pGCHI18 and pYCHI18, respectively, chitinase activity could be observed on the
      colloidal chitin agar plate from recombinant plasmid containing Escherichia coli
      transformant. Cell-free culture broth of pYCHI18 containing E. coli transformant
      decreased R. solani pathogenic activity more than 90% in the antagonistic test on
      the radish seedlings (Raphanus sativus Linn.).

PMID- 18824349
TI  - Accumulation of antioxidant phenolic constituents in submerged cultures of
      Inonotus obliquus.
AB  - Phenolic compounds produced by sclerotia of Inonotus obliquus are the active
      constituents responsible for antioxidant activities. In this study, I. obliquus
      was grown in a continuously stirred tank reactor (CSTR) to explore how it
      accumulates phenolic compounds in different culture media and whether these
      compounds possess antioxidant activities. Phenolic compounds produced by I.
      obliquus in the control medium consisted of melanins, flavonoids, polyphenols and
      small phenolics. Their accumulation was affected by adding H(2)O(2) to the
      medium, where increased levels of total intracellular phenols (TIP) and melanins,
      but less total extracellular phenol (TEP) occurred. Simultaneous exposure to
      H(2)O(2) and arbutin resulted in a further increase in TIP production and reduced
      accumulation of TEP. Both TIP and TEP obtained at different culture ages and
      media were active in scavenging superoxide anion and DPPH radicals. Therefore,
      production of phenolic compounds by I. obliquus is enhanced by imposing oxidative
      stress, which might allow it to be exploited as a reliable source of
      pharmaceutically important phenolic compounds.

PMID- 18824350
TI  - 1,2,3-Thiadiazole thioacetanilides as a novel class of potent HIV-1 non
      nucleoside reverse transcriptase inhibitors.
AB  - A novel series of 1,2,3-thiadiazole thioacetanilide (TTA) derivatives have been
      designed, synthesized and evaluated for its anti-HIV activities in MT-4 cells.
      Some derivatives proved to be highly effective in inhibiting HIV-1 replication at
      nanomolar concentrations. Among them, 2-[4-(2,4-dichlorophenyl)-1,2,3-thiadiazol
      5-ylthio]-N-(2-nitrophenyl)acetamide 7d2 was identified as the most promising
      compound (EC(50)=0.059+/-0.02 microM, CC(50)>283.25 microM, SI>4883). The
      structure-activity relationship (SAR) of these novel structural congeners is
      discussed.

PMID- 18824351
TI  - Preliminary SAR studies on non-apamin-displacing 4
      (aminomethylaryl)pyrrazolopyrimidine K(Ca) channel blockers.
AB  - An exploratory SAR study on a series of potent, non-apamin-displacing 4
      (aminomethylaryl)pyrazolopyrimidine K(Ca) channel blockers is described and their
      selectivity against K(Ca) channel subtypes is reported. The most potent analog, 5
      chloro-N-(thiophen-2-ylmethyl)pyrazolo[1,5-a]pyrimidin-7-amine (24) displayed sub
      micromolar activity in both a thallium flux and whole-cell electrophysiology
      assay and did not displace apamin in a competitive binding study.

PMID- 18824352
TI  - Inhibition of Candida albicans isocitrate lyase activity by sesterterpene
      sulfates from the tropical sponge Dysidea sp.
AB  - Seven sesterterpene sulfates (1-7) were isolated from the tropical sponge Dysidea
      sp. and their inhibitory activities against isocitrate lyase (ICL) from Candida
      albicans were evaluated. Among the isolated natural products compound 6 and 7
      were found to be strong ICL inhibitors. The isolated compounds (1-7) also showed
      potent antibacterial effect against Bacillus subtilis and Proteus vulgaris, but
      did not display antifungal activity.

PMID- 18824353
TI  - Engineering of avermectin biosynthetic genes to improve production of ivermectin
      in Streptomyces avermitilis.
AB  - Two new recombinants of avermectin polyketide synthases were constructed by
      domain and module swapping in Streptomyces avermitilis 73-12. However, only the
      strain, S. avermitilis OI-31, formed by domain substitution could produce
      ivermectin. Analysis of the ivermectin synthesized gene cluster showed that
      decreased amount of aveC transcripts was one of the factors causing low yield of
      ivermectin. Overexpression of aveC could improve ivermectin yield.

PMID- 18824354
TI  - Dividing the workload at a eukaryotic replication fork.
AB  - Efficient and accurate replication of the eukaryotic nuclear genome requires DNA
      polymerases (Pols) alpha, delta and epsilon. In all current replication fork
      models, polymerase alpha initiates replication. However, several models have been
      proposed for the roles of Pol delta and Pol epsilon in subsequent chain
      elongation and the division of labor between these two polymerases is still
      unclear. Here, we revisit this issue, considering recent studies with diagnostic
      mutator polymerases that support a model wherein Pol epsilon is primarily
      responsible for copying the leading-strand template and Pol delta is primarily
      responsible for copying the lagging-strand template. We also review earlier
      studies in light of this model and then consider prospects for future
      investigations of possible variations on this simple division of labor.

PMID- 18824355
TI  - Addition of an arch support improves the biomechanical effect of a laterally
      wedged insole.
AB  - In order to examine if the addition of an arch support could improve the
      biomechanical effect of the laterally wedged insole, three-dimensional gait
      analysis was performed on 20 healthy volunteers. Kinetic and kinematic parameters
      at the knee and subtalar joints were compared among the following four types of
      insoles; a 5-mm thick flat insole, a flat insole with an arch support (AS), a 6
      degrees inclined laterally wedged insole (LW), and a laterally wedged insole with
      an arch support (LWAS). The knee adduction moment averaged for the entire stance
      phase was reduced by the use of LW and LWAS by 7.7% and 13.3%, respectively, from
      that with FLAT. The difference in knee adduction moment between LW and LWAS was
      most obvious in the late stance, which was ascribed to the difference in the
      progression angle between those insoles. The analyses also revealed that LW
      tended to increase step width, and that such an increase was completely
      eliminated by the addition of an arch support to LW. This reduction of step width
      could be another mechanism for the further reduction of the moment with LWAS. The
      analyses of biomechanical parameters at the subtalar joints suggested that LWAS
      allowed the subject to walk in a more natural manner, while exerting greater
      biomechanical effects than LW. Thus, the addition of an arch support to the
      laterally wedged insole reduced knee adduction moment more efficiently, possibly
      through the elimination of potential negative effects of the laterally wedged
      insole.

PMID- 18824356
TI  - Rosai-Dorfman disease mimicking chronic subdural hematoma.
AB  - Rosai-Dorfman disease (RDD), otherwise known as sinus histiocytosis with massive
      lymphadenopathy, is an uncommon, benign systemic histio-proliferative disease
      characterised by massive lymphadenopathy particularly in the head and neck
      region, and is often associated with extra-nodal involvement. We report a case in
      which RDD was mistaken for a chronic subdural hematoma and surgery was attempted.

PMID- 18824357
TI  - Cerebral dural sinus thrombosis following cisplatin chemotherapy.
AB  - Two patients with cerebral dural sinus thrombosis (CST) following cisplatin
      therapy are presented. Cisplatin is a well-recognized risk factor for coagulation
      disorders and thrombosis, but is not known to be associated with CST. Clinicians
      should be aware of the potential risk for the development of CST following
      cisplatin therapy.

PMID- 18824358
TI  - A pilot study of resistance to aspirin in stroke patients.
AB  - Aspirin resistance has been shown to be a significant risk factor for recurrent
      cardiovascular ischaemic events. However, there are a lack of data correlating
      aspirin resistance and risk of cerebrovascular ischaemic events. This pilot study
      aimed to determine the prevalence of aspirin resistance in an Australian stroke
      population and to correlate aspirin resistance with an increased risk of
      ischaemic stroke. Fifty patients treated with aspirin for 2 years were tested for
      aspirin resistance using the Ultegra Rapid Platelet Function Assay (Accumetrics,
      San Diego, CA, USA) on admission to Royal Melbourne Hospital for ischaemic
      stroke. The 2-year history of ischaemic stroke and transient ischaemic attack
      (TIA) were assessed. Prevalence of aspirin resistance among our patients was 30%.
      Univariate analysis suggested a non-significant trend towards increased rate of
      previous ischaemic stroke or TIA and aspirin resistance (odds ratio, OR=3.88; 95%
      confidence interval 0.54-29.87; p=0.18). This study shows that aspirin resistance
      is prevalent within the Australian ischaemic stroke population.

PMID- 18824359
TI  - Connexin43 antisense oligodeoxynucleotide treatment down-regulates the
      inflammatory response in an in vitro interphase organotypic culture model of
      optic nerve ischaemia.
AB  - Using a model of optic nerve ischaemia, this study investigated oxygen-glucose
      deprivation (OGD) on isolated rat optic nerve segments cultured in vitro.
      Thereafter, the effect of antisense oligodeoxynucleotides (ASODN) specific to the
      gap junction protein connexin43 (Cx43) was evaluated in this same model.
      Following exposure to OGD for 2 hours, optic nerves were maintained in interphase
      organotypic culture with and without exposure to Cx43 ASODN. Optic nerves were
      sectioned at 2 hours, 6 hours, and at days 1, 2, 3 and 6 following culture. Cell
      death was quantified using propidium iodide (PI) staining and specific markers
      for Cx43, capillaries (von Willebrand factor), astrocytes (glial fibrillary
      acidic protein), microglia and endothelial cells (isolectin B4) were used to
      evaluate these parameters in conjunction with digital light and confocal
      microscopy. In this model, up-regulation of Cx43 was seen at 2 hours following
      exposure of the optic nerve to OGD and peaked at day 3. Cx43 ASODN treatment
      dampened this up-regulation. Additionally, more PI labeled cells were found in
      the centre of control optic nerve segments than in treated nerves (p<0.01).
      Controls also showed evidence of capillary breakdown and increased numbers of
      astrocytes and activated microglia compared to Cx43 ASODN treated nerves
      (p<0.05). Thus, the application of Cx43 ASODN to post-ischaemic optic nerve
      segments significantly reduced the up-regulation of Cx43 and, subsequently, the
      spread of injury and a resultant inflammatory response. Cx43 up-regulation may
      play an important role in optic nerve injury, offering a potential avenue for
      treatment in optic neuropathy.

PMID- 18824360
TI  - Utility of a patient survey in identifying fluctuations in early stage
      Parkinson's disease.
AB  - Motor and non-motor fluctuations are well known sequelae of dopaminergic
      therapies for Parkinson's disease (PD), particularly during the advanced stages.
      However, the prevalence of fluctuations early in the treatment course has been
      less well recognised and may be missed clinically if not specifically probed. We
      examined the used of a survey for this purpose. Patients to be surveyed were
      recruited by neurologists and geriatricians at 20 Australian centres. Patients
      had a diagnosis of idiopathic PD with a duration of fewer than 5 years and were
      considered by their treating physician to be non-fluctuating or had no change in
      their treatment plan in the prior 6 months. Patients, with or without assistance,
      completed a 19-item wearing-off questionnaire to assess the presence of motor and
      non-motor fluctuations that indicated early wearing-off. Investigators assessed
      the usefulness of the questionnaire in detecting fluctuations and guiding PD
      treatment. Of 105 patients recruited, 92 were eligible for analysis. There were
      56 (61%) identified as having fluctuations. Patients with wearing-off were
      younger (mean 67 vs 72 years), and more likely to have had PD for more than 3
      years. About half the patients (49%) were able to complete the questionnaire
      independently. Clinicians perceived the questionnaire as useful for detecting
      fluctuations and adjusting treatment. A simple and easily administered wearing
      off questionnaire may be useful in the early detection of fluctuations in PD
      patients and assist in guiding therapy.

PMID- 18824361
TI  - Tubular aggregate myopathy: a rare form of myopathy.
AB  - Tubular aggregate myopathy (TAM) is a rare form of myopathy with an autosomal
      dominant or recessive pattern. Four rare cases of TAM are described. All patients
      presented with muscle aches and pains, sometimes cramps. Muscle biopsies were
      snap frozen and processed for routine, special, enzyme, and immunohistochemistry.
      Tissue was also processed for electron microscopy. Muscle biopsy revealed similar
      changes characterized by subsarcolemmal accumulation of granular material that
      stained red with modified Gomori trichrome stain, intense blue with nicotinamide
      adenine dinucleotide-tetrazolium reductase, but was non-reactive to succinyl
      dehydrogenase and cytochrome oxidase stains. Ultrastructural examination showed
      aggregates of hexagonal tubules in the subsarcolemmal region, which are
      pathognomonic of this entity. This report highlights the importance of
      histochemistry and electron microscopy for accurate diagnosis; otherwise TAM can
      be misdiagnosed on clinical grounds as a metabolic or mitochondrial myopathy.

PMID- 18824362
TI  - Proteochemometrics analysis of substrate interactions with dengue virus NS3
      proteases.
AB  - The prime side specificity of dengue protease substrates was investigated by use
      of proteochemometrics, a technology for drug target interaction analysis. A set
      of 48 internally quenched peptides were designed using statistical molecular
      design (SMD) and assayed with proteases of four subtypes of dengue virus (DEN-1
      4) for Michaelis (K(m)) and cleavage rate constants (k(cat)). The data were
      subjected to proteochemometrics modeling, concomitantly modeling all peptides on
      all the four dengue proteases, which yielded highly predictive models for both
      activities. Detailed analysis of the models then showed that considerably
      differing physico-chemical properties of amino acids contribute independently to
      the K(m) and k(cat) activities. For k(cat), only P1' and P2' prime side residues
      were important, while for K(m) all four prime side residues, P1'-P4', were
      important. The models could be used to identify amino acids for each P' substrate
      position that are favorable for, respectively, high substrate affinity and
      cleavage rate.

PMID- 18824363
TI  - Synergistic interaction between p-glycoprotein modulators and epirubicine on
      resistant cancer cells.
AB  - The macrocyclic lathyrane diterpene latilagascene B, previously isolated from
      Euphorbia lagascae, was acylated to afford three new diterpene esters,
      latilagascenes G (1), H (2), and I (3), whose structures were assigned by
      spectroscopic methods. These acyl derivatives, and the macrocyclic diterpenes of
      the jatrophane-type, tuckeyanols A (4) and B (5), and euphotuckeyanol (6),
      isolated from Euphorbia tuckeyana, were tested for P-gp modulating properties on
      human MDR1 gene-transfected and parental L5178 mouse lymphoma cell lines. All the
      compounds displayed very strong activity. The molecular orbital energies (HOMO
      and LUMO) of diterpenes 1-6 and 7-13, previously isolated, have also been
      calculated in order to estimate their probable charge transfer interactions with
      P-gp. Structure-activity relationships (SAR) are discussed. Furthermore,
      compounds (1-6) were assayed, in vitro, for their antiproliferative effects in
      combination with epirubicine and all of them synergistically enhance the effect
      of the antitumor drug.

PMID- 18824364
TI  - Chemical synthesis of diastereomeric diadenosine boranophosphates (ApbA) from 2'
      O-(2-cyanoethoxymethyl)adenosine by the boranophosphotriester method.
AB  - We have synthesized diastereomerically pure diadenosine 3',5'-boranophosphates
      (Ap(b)A) by using the boranophosphotriester method from ribonucleosides protected
      with the 2'-hydroxy protecting group 2-cyanoethoxymethyl (CEM). Melting curves of
      the triple-helical complex of the dimer Ap(b)A and 2poly(U) at high ionic
      strength revealed that presumptive (Sp)-Ap(b)A had a much higher affinity and
      presumptive (Rp)-Ap(b)A a much lower affinity for poly(U) than the natural dimer
      ApA did. In contrast, the affinities of these dimers for poly(dT) were similar.
      Both the (Rp)- and the (Sp)-boranophosphate diastereomers showed much higher
      resistance to digestion by snake venom phosphodiesterase and nuclease P1 than ApA
      did. They have potential for use as synthons to be incorporated into
      boranophosphate oligonucleotides. In particular, because oligonucleotides
      containing Sp boranophosphate nucleotides are expected to bind more strongly and
      specifically to RNA than natural oligoribonucleotides do, they may find
      application in the isolation and detection of functional RNA in basic research
      and diagnostics.

PMID- 18824365
TI  - Cellular automaton model of cell response to targeted radiation.
AB  - It has been shown that the response of cells to low doses of radiation is not
      linear and cannot be accurately extrapolated from the high dose response. To
      investigate possible mechanisms involved in the behaviour of cells under very low
      doses of radiation, a cellular automaton (CA) model was created. The diffusion
      and consumption of glucose in the culture dish were computed in parallel to the
      growth of cells. A new model for calculating survival probability was introduced;
      the communication between targeted and non-targeted cells was also included.
      Early results on the response of non-confluent cells to targeted irradiation
      showed the capability of the model to take account for the non-linear response in
      the low-dose domain.

PMID- 18824366
TI  - Validation of two echocardiographic indexes to improve the diagnosis of complex
      coarctations.
AB  - OBJECTIVES: Coarctation of the aorta is one of the most common congenital heart
      defects. Its diagnosis may be difficult in the presence of a patent ductus
      arteriosus, of other complex defects or of a poor echocardiographic window. We
      sought to demonstrate that the carotid-subclavian artery index (CSA index) and
      the isthmus-descending aorta ratio (I/D ratio), two recently described
      echocardiographic indexes, are effective in detection of isolated and complex
      aortic coarctations in children younger and older than 3 months of age. The CSA
      index is the ratio of the distal aortic arch diameter to the distance between the
      left carotid artery and the left subclavian artery. It is highly suggestive of a
      coarctation when it is <1.5. The I/D ratio defined as the diameter of the isthmus
      to the diameter of the descending aorta, suggests an aortic coarctation when it
      is less than 0.64. METHODS: This is a retrospective cohort study in a tertiary
      care children's hospital. Review of all echocardiograms in children aged 0-18
      years with a diagnosis of coarctation seen at the author's institution between
      1996 and 2006. An age- and sex-matched control group without coarctation was
      constituted. Offline echocardiographic measurements of the aortic arch were
      performed in order to calculate the CSA index and I/D ratio. RESULTS: Sixty-eight
      patients were included in the coarctation group, 24 in the control group.
      Patients with coarctation had a significantly lower CSA index (0.84+/-0.39 vs
      2.65+/-0.82, p<0.0001) and I/D ratio (0.58+/-0.18 vs 0.98+/-0.19, p<0.0001) than
      patients in the control group. Associated cardiac defects and age of the child
      did not significantly alter the CSA index or the I/D ratio. CONCLUSIONS: A CSA
      index less than 1.5 is highly suggestive of coarctation independent of age and of
      the presence of other cardiac defects. I/D ratio alone is less specific than CSA
      alone at any age and for any associated cardiac lesion. The association of both
      indexes improves sensitivity and permits diagnosis of coarctation in all patients
      based solely on a bedside echocardiographic measurement.

PMID- 18824367
TI  - Huge cardiac hemangioma.

PMID- 18824368
TI  - Myocardial oxidative stress, and cell injury comparing three different techniques
      for coronary artery bypass grafting.
AB  - OBJECTIVE: Oxidative stress as a result of reperfusion injury is a known
      causative factor of cardiac muscle injury. In the peripheral blood as well in the
      coronary sinus, oxidative stress parameters and cardiac biomarkers were measured
      to investigate the different levels of oxidative stress during three different
      CABG techniques; MCABG (with minimal prime volume and warm blood cardioplegia)
      that was newly introduced in our hospital, versus OPCAB, versus our current
      standard, conventional CABG (CCABG, consisting of high volume prime and cold
      crystalloid cardioplegia). Concomitantly, cardiac biomarkers were measured to
      detect myocardial cell injury. METHODS: Thirty patients scheduled for CABG with
      the intention to treat three-vessel disease were randomly assigned for CCABG,
      MCABG or OPCAB. Perioperatively, plasma levels of malondialdehyde (MDA) as a
      marker of oxidative stress, and the allantoin/uric acid ratio (A/U ratio) as a
      marker of antioxidant activity were measured in the ascending aorta (Aa), and in
      the coronary sinus (Cs), simultaneously. Additionally peripheral (Aa) blood
      levels of heart fatty acid binding protein (HFABP), troponin T, CPK and CKMB as
      markers of myocardial injury were obtained. RESULTS: The MCABG group had
      significantly lower MDA levels in the Cs compared to the CCABG group,
      respectively, to the OPCAB group (p=0.04 and p=0.03). At all time points the A/U
      ratio in the CCABG group remained significantly higher in the Cs as well in the
      Aa samples compared to the MCABG and the OPCAB group (p<0.001, respectively,
      p<0.001, for both groups). HFABP and troponin T showed consistent curves compared
      to the CPK figure over time in all groups. CONCLUSION: In this study coronary
      sinus blood levels of oxidative stress parameters were consistently higher
      compared to peripheral blood levels. The levels were lowest in the MCABG study
      group. In this group also the lowest levels cardiac biomarkers of myocardial
      injury were found.

PMID- 18824369
TI  - Multiple independent primary cancers do not adversely affect survival of the lung
      cancer patient.
AB  - OBJECTIVE: Diagnosis of multiple independent primary cancers is increasing in
      many settings. Objectives of this study were to analyze clinical characteristics,
      organ location, and prognosis associated with the presentation of multiple
      independent primaries when a lung cancer is involved. METHODS: We analyzed all
      patients with a histology-proven diagnosis of lung cancer registered from January
      1990 to December 2004 at the Tumor Registry of the Hospital del Mar, Barcelona.
      We compared 1686 patients presenting a lung cancer as unique primary versus 228
      patients presenting a lung cancer and another independent primary. Cofactors
      included age, sex, smoking habit, lung cancer histology and stage, type and
      intention of treatment, organ location of the other cancer, and survival from the
      date of lung cancer diagnosis. RESULTS: Seventy percent of the other cancers were
      tobacco-related. Independent risk factors of cancer multiplicity were smoking
      (OR: 3.99; 95% CI: 1.4-11.2), lung cancer stages I (OR: 1.84; 95% CI: 1.2-2.9)
      and II (OR: 3.25; 95% CI: 1.7-6.3), and older age (OR: 3.11; 95% CI: 1.9-5.1).
      Once adjusted by age and sex, the main determinant of survival was lung cancer
      stage rather than cancer multiplicity. However, patients with multiple cancers
      presented a slightly better survival than patients with a lung cancer as unique
      primary. When analyzed by subgroups, survival was higher in patients with the
      lung cancer first (HR: 0.44; 95% CI: 0.24-0.80), and in patients with the other
      cancer first (HR: 0.80; 95% CI: 0.65-0.99), but it was not different in the
      patients with a lung cancer and a synchronous other cancer (HR: 0.80; 95% CI:
      0.52-1.15). CONCLUSIONS: The risk of developing a second independent cancer was
      strongly associated with tobacco smoking. Cancer multiplicity was not associated
      with a worse prognosis. As a consequence, when a first primary tobacco-related
      cancer is treated with curative intention, patients should be closely followed up
      for an early diagnosis of a possible new independent cancer; and if diagnosed,
      treatment to cure should be considered as the first option.

PMID- 18824370
TI  - Incidence, management and clinical outcomes of patients with airway complications
      following lung transplantation.
AB  - OBJECTIVE: Airway complications (AC) remain a significant contributing factor of
      morbidity after lung transplantation (LT). The aim of this study was to identify
      risk factors for AC, and to review the outcomes after endoscopic and surgical
      treatment. METHODS: From 1993 to 2006, 255 patients underwent LT. Seven
      retransplants and 34 patients not surviving beyond 7 days were excluded. The
      remaining patients were: 124 double LT (DLT), 85 single LT (SLT), 3 lobar LT and
      2 liver-DLT, comprising 343 bronchial anastomoses at risk. Donor lungs were
      flushed with either modified Eurocollins or Perfadex. Bronchial anastomoses were
      telescoped when needed. Donor and recipient variables were recorded and analyzed
      by univariate and multivariate tests to identify risk factors for AC, and to
      assess differences between both complicated and non-complicated groups. RESULTS:
      Among 343 bronchial anastomoses, 31 presented AC (9%) in 27 patients (12.6%): 22
      stenoses, 5 dehiscences, and 4 malacias, at 2.6+/-1.7 months post-transplant.
      Indications were 7 emphysema, 3 Alpha-1-antitrypsin deficiency, 12 cystic
      fibrosis (p=0.007), 4 pulmonary fibrosis, and 1 bronchiectasis. AC were observed
      in 4 SLT and 23 DLT (p=0.005). Incidence of AC did not differ between telescoped
      and non-telescoped anastomoses. By univariate analysis, AC were more frequent in
      grafts preserved with modified Eurocollins (p=0.033), CMV infection/disease
      (p=0.027) and airway colonizations post-transplant (p=0.021). Other donor and
      recipient variables did not differ between groups. By multivariate analysis,
      intubation longer than 72 h, DLT, and airway colonizations post-transplant
      remained independently associated with AC. Survival did not differ between
      groups. Most patients were successfully treated with endoscopic procedures; three
      required reoperation (lobectomy, pneumonectomy, retransplantation). AC related
      mortality was 1%. CONCLUSIONS: The incidence of AC after LT is 12.6% with a
      related mortality of 1%, irrespective of the technique of bronchial anastomosis
      performed. DLT, airway colonizations, and prolonged intubation post-transplant
      are associated with AC. Either endoscopic procedures or surgical therapy resolve
      these complications in most cases.

PMID- 18824371
TI  - Pulmonary metastases of breast cancer. When is resection indicated?
AB  - OBJECTIVE: While resection of pulmonary metastases is a common treatment in other
      primaries, the role of breast cancer metastasectomy is still unclear. The
      objective of the present study was to investigate the clinical outcome of our
      operated patients with pulmonary breast cancer metastases and discuss the
      different indications for metastasectomy. METHODS: From January 1998 to December
      2007 we retrospectively analysed 47 patients with histologically proven pulmonary
      metastases from breast cancer. The mean age of the 47 female patients was 56.2
      years, the median disease-free interval (DFI) was 3.66 (0-25.8) years and the
      median follow-up was 20.6 months (3.2-110). RESULTS: The grading of the
      metastases was higher than the primary tumour in 12 of 45 (26.7%) and lower in 6
      of 45 (13.3%) patients. R0, R1 and R2 resections were achieved in 27, 6 and 14
      cases. The oestrogen receptor status of the metastases differed from the primary
      tumour in 11 out of 39 (28.2%) tested cases. Her2-neu receptor status differed in
      4 out of 16 tested patients. The histological reports described a tumour spread
      around the metastasis in lymph or blood vessels in at least one resection
      specimen in 25 out of 47 (53.2%) patients. The rate of major complications was
      5.8%. The overall survival from the first pulmonary metastasectomy was 32 months
      with a 5-year survival of 36%. The main prognostic factor was the oestrogen
      receptor status with a 5-year survival for receptor positive patients of 76% and
      12.1% for receptor negative ones (p=0.002). A similar survival difference was
      found for the status of Her2-neu receptor (p=0.037). No prognostic influence
      could be demonstrated for age, number of metastases, initial tumour stage,
      complete versus incomplete resection, lymphatic spread, lymph node or parietal
      pleural involvement. CONCLUSION: The gain in life expectancy in breast cancer
      patients with pulmonary metastases is based on chemotherapy and antihormone
      treatment. Tissue of the lung metastasis is needed to adjust medical therapy to
      oestrogen and Her2-neu expression and to reliably rule out primary lung cancer.
      In case of proved pulmonary metastases, the level of evidence for a curative
      approach is low but some patients might benefit.

PMID- 18824372
TI  - A novel technique to prevent intra-operative pneumothorax in awake coronary
      artery bypass grafting: biomaterial neo-pleura.
AB  - OBJECTIVE: Pneumothorax caused by damaged pleura represents the biggest obstacle
      in awake coronary artery bypass grafting. In order to safely perform this
      surgery, a new technique was developed to close the damaged pleura. METHODS: A
      rub-and-spray method was employed using polyglycolic acid nonwoven fabric and
      fibrin glue. At first, some fibrinogen solution was rubbed on the edge of the
      pleural defect and then the PGA fabric was placed and the fibrinogen and thrombin
      solutions were sprayed. Using a thorax model, the burst pressure caused by
      positive pressure and the influence of negative pressure, moisture, time,
      continuous respiratory movement and pleural defect size were examined. In an
      animal experiment using pigs, the duration spent on repair was measured and any
      air leakage from the pleura was also identified. RESULTS: In the thorax model,
      the burst pressure was 355.9+/-55.8 mmHg with positive pressure and no
      significant difference in negative pressure, moisture, time and respiratory
      moment was identified. However, there was a significant difference in the defect
      size. In the animal model, repair was easily achieved regardless of the defect
      size or location and air leakage was not seen after repair. The average duration
      of repair was 21.0s. CONCLUSIONS: The present method achieved a strong closure
      with sufficient durability. Since the fabric is soft and flexible and suturing is
      not required, moving and fragile pleura can be easily repaired regardless of the
      defect location and size. Once established, the present method may be used in
      other forms of awake thoracic surgery or reconstruction of the thorax.

PMID- 18824374
TI  - Characterization of O(2) ((1)delta(g))-derived oxidation products of tryptophan:
      a combination of tandem mass spectrometry analyses and isotopic labeling studies.
AB  - The fragmentation mechanisms of singlet oxygen [O(2) ((1)Delta(g))]-derived
      oxidation products of tryptophan (W) were analyzed using collision-induced
      dissociation coupled with (18)O-isotopic labeling experiments and accurate mass
      measurements. The five identified oxidized products, namely two isomeric alcohols
      (trans and cis WOH), two isomeric hydroperoxides (trans and cis WOOH), and N
      formylkynurenine (FMK), were shown to share some common fragment ions and losses
      of small neutral molecules. Conversely, each oxidation product has its own
      fragmentation mechanism and intermediates, which were confirmed by (18)O-labeling
      studies. Isomeric WOH lost mainly H(2)O + CO, while WOOH showed preferential
      elimination of C(2)H(5)NO(3) by two distinct mechanisms. Differences in the
      spatial arrangement of the two isomeric WOHs led to differences in the
      intensities of the fragment ions. The same behavior was also found for trans and
      cis WOOH. FMK was shown to dissociate by a diverse range of mechanisms, with the
      loss of ammonia the most favored route. MS/MS analyses, (18)O-labeling, and
      H(2)(18)O experiments demonstrated the ability of FMK to exchange its oxygen
      atoms with water. Moreover, this approach also revealed that the carbonyl group
      has more pronounced oxygen exchange ability compared with the formyl group. The
      understanding of fragmentation mechanisms involved in O(2) ((1)Delta(g))-mediated
      oxidation of W provides a useful step toward the structural characterization of
      oxidized peptides and proteins.

PMID- 18824375
TI  - A bi-dimensional index for the selective assessment of myoelectric manifestations
      of peripheral and central muscle fatigue.
AB  - Two physiological factors are assumed in this paper to mainly determine the
      myoelectric manifestations of fatigue: (1) the decrease of the conduction
      velocity (CV) of motor unit action potentials (MUAP) (peripheral fatigue), and
      (2) the increase of MU synchronization by the central nervous system (central
      fatigue). To describe separately the peripheral and central components of the
      myoelectric manifestations of fatigue, we investigated the following indexes: (1)
      mean spectral frequency - MNF, (2) median spectral frequency - MDF, (3) root mean
      square - RMS, (4) average rectified value - ARV, (5) estimation of muscle fiber
      conduction velocity - ECV, (6) percentage of determinism - %DET, (7) spectral
      indexes defined as the ratio between signal spectral moments - FI(k), (8) MNF
      estimated by autoregressive analysis - MNF(AR), (9) MNF estimated by Choi
      Williams time-frequency representation - MNF(CWD), (10) MNF estimated by
      continuous wavelet transform - MNF(CWT), (11) signal entropy - S, (12) fractal
      dimension - FD. The indexes were tested with a set of synthetic EMG signals, with
      different CV distribution and level of MU synchronization. The indexes were
      calculated on epochs of 0.5s. It was observed that ECV is uncorrelated with the
      level of simulated synchronization (promising index of peripheral fatigue). On
      the other hand FD was the index least affected by CV changes and most related to
      the level of synchronism (promising index of central fatigue). A representative
      application to some experimental signals from vastus lateralis muscle during an
      isometric endurance test supported the results of the simulations. The vector
      (ECV, FD) is suggested to provide selective indications of peripheral and central
      fatigue. The description of EMG fatigue by a bi-dimensional vector opens new
      perspectives in the assessment of muscle properties, with potential application
      in both clinical and sport sciences.

PMID- 18824376
TI  - Three-dimensional reconstructed contrast-enhanced MR angiography for internal
      iliac artery branch visualization before uterine artery embolization.
AB  - PURPOSE: To evaluate the feasibility of three-dimensional (3D) reconstructed
      contrast-enhanced (CE) magnetic resonance (MR) angiography in mapping the pelvic
      arteries in women before uterine artery embolization (UAE). MATERIALS AND
      METHODS: CE MR angiography studies before UAE in 49 women (age range, 38-57
      years; mean, 47.04 y +/- 4.7 [SD]) who underwent UAE for uterine leiomyomas
      between February 2005 and February 2007 were retrospectively evaluated by two
      radiologists in consensus. Studies were performed on a 1.5-T MR unit with a 3D
      fast low-angle shot sequence in the coronal direction. Reconstruction was
      performed with 3D computed tomographic angiography reconstruction software.
      RESULTS: In the current study, 98 internal iliac arteries (IIAs) from 49 women
      were studied. The superior and inferior gluteal arteries were visualized in all
      cases (N = 98; 100%), the lateral sacral artery in 86 cases (88%), the iliolumbar
      artery in 84 (86%), the obturator artery in 81 (83%), the internal pudendal
      artery in 96 (98%), and the uterine artery in 95 (97%). The superior vesical and
      middle rectal arteries were seen in 21 (21%) and 11 (11%) cases, respectively.
      The mean length of the uterine artery was 12.56 cm (range, 4.6-22.2 cm), and it
      showed the longest traceable length among all branches. The uterine artery showed
      five patterns of origin. The superior gluteal artery showed constant origin from
      the posterior division of the IIA, whereas the iliolumbar and obturator arteries
      showed the most variations in origin. CONCLUSIONS: Three-dimensional
      reconstructed CE MR angiography can detect most branches of the IIA in addition
      to their point of origin. Therefore, it can be used as a mapping tool of the
      pelvic arterial tree before UAE.

PMID- 18824377
TI  - Role of connexin-43 hemichannels in the pathogenesis of Yersinia enterocolitica.
AB  - Connexin (Cx) channels are sites of cytoplasmic communication between contacting
      cells. Evidence indicates that the opening of hemichannels occurs under both
      physiological and pathological conditions. In this paper, the involvement of Cx
      43 hemichannels is demonstrated in the pathogenesis of Yersinia. Parental HeLa
      cells and transfected HeLa cells stably expressing Cx-43 (HCx43) were infected
      with Yersiniaenterocolitica, and bacterial uptake was measured by the colony
      forming unit method. Bacterial uptake was higher in HCx43 cells than in parental
      cells and was inhibited by the Cx channel blocker, 18-alpha-glycyrrhetinic acid
      (AGA). The inhibitory effect of AGA was more pronounced on the Y. enterocolitica
      uptake by HCx43 cells than by parental cells. The ability of HCx43 cells to
      incorporate the permeable fluorescent tracer Lucifer Yellow (LY) was assessed.
      Dye incorporation was inhibited by AGA, whereas Y. enterocolitica infection of
      HCx43 cells increased LY incorporation. Western blotting analysis demonstrated
      that Y. enterocolitica infection of HCx43 cells induced tyrosine phosphorylation
      of Cx-43, thus supporting a critical role for Cx-43 in the strategies exploited
      by bacterial pathogens to invade non-phagocytic cells.

PMID- 18824378
TI  - What would the brain look like in Angelman syndrome?

PMID- 18824379
TI  - Transverse NMR relaxation in magnetically heterogeneous media.
AB  - We consider the NMR signal from a permeable medium with a heterogeneous Larmor
      frequency component that varies on a scale comparable to the spin-carrier
      diffusion length. We focus on the mesoscopic part of the transverse relaxation,
      that occurs due to dispersion of precession phases of spins accumulated during
      diffusive motion. By relating the spectral lineshape to correlation functions of
      the spatially varying Larmor frequency, we demonstrate how the correlation length
      and the variance of the Larmor frequency distribution can be determined from the
      NMR spectrum. We corroborate our results by numerical simulations, and apply them
      to quantify human blood spectra.

PMID- 18824380
TI  - Predicting growth in response to growth hormone treatment.
AB  - The use of growth hormone (GH) to treat children who have disturbances of growth
      is complicated by variability both within and across diagnostic groups, and at
      the start of and throughout treatment. Growth prediction models are important
      tools in the effort to account for these sources of variability and tailor GH
      treatment to each patient's needs. This review considers the methodological
      approach taken to the development of models from data in large databases such as
      the Pfizer International Growth Database (KIGS); it also assesses the limitations
      of these models and their data sources, and the potential for improvements. While
      all aspects of model development bear continued scrutiny and improvement, the
      incorporation of more predictors is key if treatment outcomes are to be optimized
      in terms of efficacy, safety and cost.

PMID- 18824381
TI  - Functional and metabolic implications of biotin deficiency for the rat heart.
AB  - The tricarboxylic acid (TCA) cycle is the main ATP provider for the heart. TCA
      carbons must be replenished by anaplerosis for normal cardiac function. Biotin is
      cofactor of the anaplerotic enzymes pyruvate and propionyl-CoA carboxylases.
      Here, we found that in biotin deficient rats, both carboxylases decreased 90% in
      adipose tissue, jejunum and spleen, but in heart they conserved about 60%
      residual activity. We then investigated if under biotin deficiency (BtDEF), the
      heart is able to maintain its function in vivo and in isolated conditions, and
      during ischemia and reperfusion, where metabolism drastically shifts from
      oxidative to mainly glycolytic. Neither glucose nor octanoate oxidation were
      severely affected in BtDEF hearts, as assessed by mechanical performance, oxygen
      uptake or high-energy metabolite content; however, myocardial hexokinase activity
      and lactate concentration were reduced in deficient hearts. When challenged by
      ischemia and reperfusion injury, BtDEF hearts did not suffer more damage than the
      controls, although they lowered significantly their performance, when changed to
      ischemic conditions, which may have clinical implications. Post-ischemic increase
      in ADP/ATP ratio was similar in both groups, but during reperfusion there was
      higher rhythm perturbation in BtDEF hearts. By being relatively insensitive to
      biotin deficiency, cardiac tissue seems to be able to replenish TCA cycle
      intermediates and to maintain ATP synthesis.

PMID- 18824382
TI  - Can glycaemic variability, as calculated from blood glucose self-monitoring,
      predict the development of complications in type 1 diabetes over a decade?
AB  - AIMS: Is glycaemic variability an independent risk factor for the development of
      microvascular complications in addition to average glycaemia, as assessed by
      glycated haemoglobin (HbA(1c))? In this study, an 11-year follow-up was carried
      out in patients with type 1 diabetes. The standard deviation of blood glucose
      (SDBG) concentration, an index of glycaemic variability, was calculated from self
      monitored blood glucose data at baseline. METHODS: A total of 100 patients were
      randomly selected from 442 consecutive type 1 diabetic patients attending our
      outpatients clinic. SDBG was calculated from 70 measurements taken over a period
      of four weeks. Onset and progression of micro- and macrovascular complications
      were recorded over the 11-year follow-up. RESULTS: As expected, the prevalence of
      complications increased over time. Statistical analyses showed that HbA(1c) was
      an independent predictor of the incidence (P=0.004) and prevalence (P=0.01) of
      nephropathy. SDBG was found to be a predictor of the prevalence of peripheral
      neuropathy (P=0.03), and showed borderline significance in predicting the
      incidence of peripheral neuropathy (P=0.07). SDBG was also a highly significant
      predictor of hypoglycaemic unawareness (P=0.001). CONCLUSIONS: We conclude that
      variability of blood glucose may be important in the development of peripheral
      neuropathy in patients with type 1 diabetes, and that the nervous system may be
      particularly vulnerable to glycaemic variability.

PMID- 18824383
TI  - [The use of breast cancer subtype classification to predict local and distant
      recurrence. A review].
AB  - In breast cancer, optimal locoregional treatment allows high local control rates
      and impact long-term survival. The Early Breast Cancer Trialists Collaborative
      Group (EBCTCG) meta-analysis data showed that radiation therapy (RT) can decrease
      the risk of breast cancer death at 15 years. In the adjuvant setting, whole
      breast RT remains the standard of care. Adjuvant systemic therapies, RT
      indications, techniques and volumes are determined according to the known
      standard prognosis factors such as age, tumor size and location, nodal
      involvement, grade, hormone receptors status, proliferative index and
      lymphovascular invasion. One of the future challenges in breast cancer management
      is to determine new prognosis and predictive factors that could help to define
      the subgroups of patients, who will either really benefit from new treatment
      strategies or particular RT techniques, or for those for whom aggressive local
      therapeutic option is not needed, as their prognosis is mainly related to an
      early risk of metastatic diffusion. In the new era of fine biological diagnosis,
      a better understanding of tumor biology allows a significant development of
      targeted therapies. Adjuvant strategies including locoregional RT have to be
      based on the tailored treatment concept. These strategies have to take into
      account not only the patients profiles regarding the well-established parameters,
      but also the tumor biology, the new breast cancer subtype classification and gene
      profiles.

PMID- 18824384
TI  - [Brachytherapy for head and neck cancers (nasopharynx excluded)].
AB  - Brachytherapy is one of the standard treatments of head and neck cancers. The
      main indications are: the oral cavity, the oropharynx, the lips, the peri
      orificial skin carcinomas on the face, the postoperative treatments for T1-2/N0
      cancers of the oral cavity with close or positive margins, the second cancers in
      previously irradiated areas, the intra-operative brachytherapy for recurrent
      cervical lymph node metastases from previously irradiated tissues after maximal
      surgical debulking. The major prognostic factors published allowed to improve the
      technique: using a leaded protection of the mandible, the intersource spacing
      (1,2-1,4 cm), the volume treated (30 cm3, i.e. three loops), the safety margin (5
      mm), the dose rate (0,5 Gy/h), the total dose (65 Gy in case of exclusive
      brachytherapy, 25 Gy in case of a combination of external beam irradiation [50
      Gy] and brachytherapy in the oropharyngeal carcinomas, 35 Gy in case of a
      combination of external beam irradiation [40 Gy] and brachytherapy in the oral
      cavity carcinomas, 60 Gy in case of a second cancer in previous irradiated
      tissues), the delay between external irradiation and brachytherapy (< 20 days).
      The pulse dose rate brachytherapy should improve results with the control of the
      dose rate and the optimization of the dose distribution. For high dose rate
      brachytherapy, more results are needed to recommend this technique for routine
      use.

PMID- 18824385
TI  - Is there a role for anticonvulsants in the management of rheumatic pain?

PMID- 18824386
TI  - [Median nerve entrapment after fracture dislocation of the elbow: a two-cases
      report].
AB  - The median nerve entrapment after elbow-dislocation is rare. We report two cases
      of fracture dislocation elbow completed by entrapment of median nerve occurred
      after reduction in two children. For both cases, the diagnosis of entrapment was
      made some months later after injury. Median nerve graft was performed after nerve
      resection. The nerve recovery was satisfactory at the final follow-up. This nerve
      complication should be suspected systematically before and after reduction of all
      dislocation of the elbow in the children. The indication of nerve release or
      nerve graft depends on the entrapment and the delay of the palsy.

PMID- 18824387
TI  - [Treatment of genital prolapse in young women: sacrohysteropexy or vaginal
      route?].
AB  - Even if genital prolapse does particularly affect the elder woman, we often have
      to face a surgical demand with conservation of the uterus from a patient less
      than 50 years. Before making the decision of treating a non life-threatening
      symptom by a specific surgical technique, it is important to ask who should be
      operated and when. Then, the route of the surgery has to be chosen considering
      that the woman wants to preserve her fertility. In the past decade, some surgical
      acts, like the sacrohysteropexy, were known as having poorer results if the women
      got pregnant. Thus, if there was a persistent childbearing desire, more
      interventions allowing pregnancy (like the Manchester's or the Richardson's
      procedures) were preferred. Nowadays, the sacrohysteropexy is considered as the
      gold standard technique, but one question is coming out: could we substitute this
      traditional surgery by a vaginal repair with meshes? Despite the big diversity of
      the so-called "sacrohysteropexy", we think that it remains the first choice
      technique to cure a young woman. Vaginal meshes have too high a rate of morbidity
      (especially on sexual activity) to be considered as the best surgical treatment.
      But this question could probably find another answer in the future, when all the
      studies about the component of the meshes will be finished.

PMID- 18824388
TI  - [Against systematic labor induction "at" 41 weeks of gestation and zero days].

PMID- 18824389
TI  - [Maternal death after spontaneous rupture of a uterine artery immediately
      following delivery: a case report].
AB  - We report the case of a maternal death occurring after spontaneous rupture of a
      uterine artery immediately following delivery. The patient presented abdominal
      pain and a collapsus one hour after a normal delivery. Laparotomy revealed
      massive haemoperitoneum and intraperitoneal bleeding from the right uterine
      artery. Ligature of the uterine artery and hemostasis hysterectomy were performed
      but the patient died of multivisceral failure 18 h after the delivery. This is
      the first case report of maternal death occurring after spontaneous rupture of a
      uterine artery.

PMID- 18824390
TI  - Alpha-synuclein multiplications with parkinsonism, dementia or progressive
      myoclonus?
AB  - Duplications and triplications of the alpha-synuclein (SNCA) gene have been
      reported in Parkinson's disease patients belonging to the Southern Swedish
      "Lister family". Further genealogical research has now shown that these
      individuals are descended from a large kindred characterized by Herman Lundborg
      in 1901-1913. In the expanded pedigree, a total of 25 individuals had Parkinson's
      disease with an autosomal dominant pattern of inheritance. Hereditary dementia,
      and, historically, dementia praecox have been described in other family members.
      Furthermore, an autosomal recessively inherited pediatric disease with nocturnal
      tonic-clonic fits, subsequent progressive myoclonus, startle reactions, tremor
      and muscle rigidity was described by Lundborg in the same pedigree. The entity
      was later designated Unverricht-Lundborg disease (ULD) or progressive myoclonus
      epilepsy type 1 (EPM1). However, Lundborg's clinical description of this disease,
      based on 17 patients within this kindred, differs from the modern definition of
      EPM1, which relies on patients with a mutation in the cystatin B (CSTB) gene. We
      hypothesize that the former pediatric disease, as well as the parkinsonism and
      dementia phenotypes, are associated with duplications, triplications and possibly
      higher-order multiplications of the alpha-synuclein (SNCA) gene. This hypothesis
      is supported by the distribution of afflicted family members within the pedigree
      and by recently obtained genealogical information.

PMID- 18824391
TI  - Trunk muscle response to various protocols of lumbar traction.
AB  - The purpose of this study was to compare trunk muscle activity, spinal
      decompression force, and trunk flexibility resulting from various protocols of
      spinal traction. Four experiments explored the effects of (1) sinusoidal,
      triangular, square, and continuous distraction-force waveforms, (2) 0, 10, 20,
      and 30 degrees of pull angle, (3) superimposed low, medium and high frequency
      force oscillations, and (4) sham traction. Nineteen healthy subjects volunteered
      for this study. Surface EMG was recorded during traction and later used in a
      biomechanical model to estimate spine decompression force. Trunk flexibility was
      measured before and after each treatment. There were no differences in muscle
      activity between any of the experimental conditions except the thoracic erector
      spinae muscle, which had lower EMG during continuous compared to sinusoidal
      distraction-force waveform (p=0.02). Thoracic and lumbar erector spinae muscles
      were significantly less active during sham than real traction (p=0.01 and p=0.04,
      respectively). The estimated L4-L5 spine compression force was 25N. Trunk
      flexibility decreased after each experimental session (p=0.01), and there were no
      differences between sessions. Our results suggest that the trunk muscle activity
      is minimal and point toward fluid exchange in the disc as one of the key
      biomechanical effects of spinal traction.

PMID- 18824392
TI  - The reliability and validity of assessing medio-lateral patellar position: a
      systematic review.
AB  - Medio-lateral patellar position is regarded as a sign of patellofemoral pain
      syndrome and patellar instability. Its assessment is important in accurately
      performing patellofemoral therapeutic taping techniques. The purpose of this
      paper is to systematically review the literature to determine the reliability and
      validity of evaluating medio-lateral patellar position. An electronic database
      search was performed accessing AMED, British Nursing Index, CINAHL, the Cochrane
      database, EMBASE, Ovid Medline, Physiotherapy Evidence Database (PEDro), PubMed
      and Zetoc to July 2008. Conference proceedings and grey literature were also
      scrutinised for future publications. All human subject, clinical trials,
      assessing the inter- or intra-tester reliability, or the criterion validity, were
      included. A CASP tool was employed to evaluate methodological quality. Nine
      papers including 237 patients (306 knees) were reviewed. The findings of this
      review suggest that the intra-tester reliability of assessing medio-lateral
      patellar position is good, but that inter-tester reliability is variable. The
      criterion validity of this test is at worse moderate. These are based on a
      limited evidence-base. Further study is recommended to compare the McConnell
      (1986) [McConnell J. The management of chondromalacia patellae: a long term
      solution. Australian Journal of Physiotherapy 1986;32(4):215-23] and Herrington
      (2002) [Herrington LC. The inter-tester reliability of a clinical measurement
      used to determine the medial/lateral orientation of the patella. Manual Therapy
      2002;7(3):163-7] methods of assessing medio-lateral patellar position in patients
      with well-defined patellofemoral disorders.

PMID- 18824393
TI  - Validity of the Neck Disability Index and Neck Pain and Disability Scale for
      measuring disability associated with chronic, non-traumatic neck pain.
AB  - The purpose of this study was to evaluate the construct and content validity of
      the Neck Disability Index (NDI) and the Neck Pain and Disability Scale (NPAD) in
      patients with chronic, non-traumatic neck pain. Twenty patients (mean age=64.5
      years) completed a patient-specific questionnaire, the Problem Elicitation
      Technique (PET), followed by the NDI and NPAD. Content validity was assessed by
      comparing the items of the NDI and NPAD with problems identified from the PET.
      Construct validity of the fixed-item questionnaires was examined by establishing
      the correlation with each other, and with the PET score. Eleven common problems
      were identified by patients through the PET, of which six were included in the
      NDI and seven included in the NPAD. The NDI and NPAD scores were strongly
      correlated (r=0.86, p<0.01), while the correlation between the PET and the fixed
      item questionnaires was moderate (NDI: r=0.62, p<0.01; NPAD: r=0.71, p<0.01).
      Both the NDI and the NPAD include most of the functional problems common to this
      patient group, and display good content validity. The PET is better able to
      evaluate the problems specific to the individual patient and is therefore
      measuring a somewhat different construct to the fixed-item questionnaires.

PMID- 18824394
TI  - Evaluation of stretching position by measurement of strain on the ilio-femoral
      ligaments: an in vitro simulation using trans-lumbar cadaver specimens.
AB  - The ilio-femoral ligament is known to cause flexion contracture of the hip joint.
      Stretching positioning is intended to elongate the ilio-femoral ligaments,
      however, no quantitative analysis to measure the effect of stretching positions
      on the ligament has yet been performed. Strains on the superior and inferior ilio
      femoral ligaments in 8 fresh/frozen trans-lumbar cadaveric hip joints were
      measured using a displacement sensor, and the range of movement of the hip joints
      was recorded using a 3Space Magnetic Sensor. Reference length (L(0)) for each
      ligament was determined to measure strain on the ligaments. Hip positions at 10
      degrees adduction with maximal external rotation, 20 degrees adduction with
      maximal external rotation, and maximal external rotation showed larger strain for
      the superior ilio-femoral ligament than the value obtained from L(0), and hip
      positions at 20 degrees external rotation with maximal extension and maximal
      extension had larger strain for the inferior ilio-femoral ligament than the value
      obtained from L(0) (p<0.05). Superior and inferior ilio-femoral ligaments
      exhibited positive strain values with specific stretching positions. Selective
      stretching for the ilio-femoral ligaments may contribute to achieve lengthening
      of the ligaments to treat flexion contracture of the hip joint.

PMID- 18824395
TI  - The use of osteopathic manipulative treatment as adjuvant therapy in patients
      with peripheral arterial disease.
AB  - Peripheral arterial disease (PAD) is a manifestation of systemic atherosclerosis
      associated with impaired endothelial function and intermittent claudication is
      the hallmark symptom. Hypothesizing that osteopathic manipulative treatment (OMT)
      may represent a non-pharmacological therapeutic option in PAD, we examined
      endothelial function and lifestyle modifications in 15 intermittent claudication
      patients receiving osteopathic treatment (OMT group) and 15 intermittent
      claudication patients matched for age, sex and medical treatment (control group).
      Compared to the control group, the OMT group had a significant increase in
      brachial flow-mediated vasodilation, ankle/brachial pressure index, treadmill
      testing and physical health component of life quality (all p<0.05) from the
      beginning to the end of the study. At univariate analysis in the OMT group there
      was a negative correlation between changes in brachial flow-mediated vasodilation
      and IL-6 levels (r=-0.30; p=0.04) and a positive one between claudication pain
      time and physical function score (r=0.50; p=0.05). In conclusion, despite the
      relatively few patients in our study, these results suggest that OMT
      significantly improves endothelial function and functional performance in
      intermittent claudication patients along with benefits in quality of life. This
      novel treatment combined with drug and lifestyle modification might be an
      effective alternative to traditional training based on exercise.

PMID- 18824396
TI  - Strangers in the matrix: plant cell walls and pathogen susceptibility.
AB  - Early in infection, pathogens encounter the outer wall of plant cells. Because
      pathogen hydrolases targeting the plant cell wall are well-known components of
      virulence, it has been assumed that wall disassembly by the plant itself also
      contributes to susceptibility, and now this has been established experimentally.
      Understanding how plant morphological and developmental remodeling and pathogen
      cell wall targeted virulence influence infections provides new perspectives about
      plant-pathogen interactions. The plant cell wall can be an effective physical
      barrier to pathogens, but also it is a matrix where many proteins involved in
      pathogen perception are delivered. By breaching the wall, a pathogen potentially
      reveals itself to the plant and activates responses, setting off events that
      might halt or limit its advance.

PMID- 18824397
TI  - Transposing phytochrome into the nucleus.
AB  - To control many physiological responses, phytochromes directly modulate gene
      expression. A key regulatory event in this signal transduction pathway is the
      light-controlled translocation of the photoreceptor from the cytoplasm into the
      nucleus. Recent publications are beginning to shed light on the molecular
      mechanisms underlying this central control point. Interestingly, there is a
      specific mechanism for phytochrome A (phyA) nuclear accumulation. The dedicated
      phyA nuclear import pathway might be important for the distinct photosensory
      specificity of this atypical phytochrome. Recent studies in the field also
      provide a starting point for investigating how the different subcellular pools of
      phytochrome can control distinct responses to light.

PMID- 18824398
TI  - L-Ascorbate biosynthesis in higher plants: the role of VTC2.
AB  - In the past year, the last missing enzyme of the L-galactose pathway, the linear
      form of which appears to represent the major biosynthetic route to L-ascorbate
      (vitamin C) in higher plants, has been identified as a GDP-L-galactose
      phosphorylase. This enzyme catalyzes the first committed step in the synthesis of
      that vital antioxidant and enzyme cofactor. Here, we discuss how GDP-L-galactose
      phosphorylase enzymes, encoded in Arabidopsis by the paralogous VTC2 and VTC5
      genes, function in concert with the other enzymes of the L-galactose pathway to
      provide plants with the appropriate levels of L-ascorbate. We hypothesize that
      regulation of L-ascorbate biosynthesis might occur at more than one step and
      warrants further investigation to allow for the manipulation of vitamin C levels
      in plants.

PMID- 18824399
TI  - Timing is everything: regulatory overlap in plant cell death.
AB  - Plant development and defence are intimately connected to programmed cell death
      (PCD). PCD can occur after environmental cues such as pathogen infection,
      mechanical damage or abiotic stress. However, PCD also constitutes an essential
      feature of various aspects of growth and development. Despite the differences in
      stimuli, the subsequent steps leading to programmed cellular death show
      considerable commonality, reflecting the essential and overlapping roles of
      individual regulatory components in these processes. These components can
      function as positive or negative regulators and can have contrasting functions
      depending on the form of cell death.

PMID- 18824400
TI  - The relocation of starch metabolism to chloroplasts: when, why and how.
AB  - Plastid endosymbiosis was accompanied by the appearance of a novel type of semi
      cristalline storage polysaccharide (starch). Interestingly, starch is found in
      the cytoplasm of Rhodophyceae and Glaucophyta but is localized to the chloroplast
      stroma of Chloroplastida. The pathway is presumed to have been cytosolic in the
      common ancestor of the three Archaeplastida lineages. The means by which in green
      plants and algae an entire suite of nuclear-encoded starch-metabolism genes could
      have had their protein products rewired simultaneously to plastids are unclear.
      This opinion article reviews the timing and the possible reasons underlying this
      rewiring and proposes a hypothesis that explains its mechanism. The consequences
      of this mechanism on the complexity of starch metabolism in Chloroplastida are
      discussed.

PMID- 18824401
TI  - Endoplasmic reticulum bodies: solving the insoluble.
AB  - Plant cells produce and accumulate insoluble triglycerides, proteins, and rubber
      that are assembled into inert, ER-derived organelles broadly termed as ER bodies.
      ER bodies appear to originate from tubular ER domains that are maintained by
      cytoskeletal interactions and integral ER proteins. ER bodies sequestering
      insoluble substances usually are transferred to the vacuole but sometimes remain
      as cytoplasmic organelles. Some otherwise soluble ER-synthesized proteins are
      converted to insoluble aggregates to produce ER bodies for transfer to the
      vacuole. This process constitutes an alternate secretory system to assemble and
      traffic transport-incompetent insoluble materials.

PMID- 18824402
TI  - Plasmodesmata: structure, function and biogenesis.
AB  - Plasmodesmata remain one of the outstanding mysteries in plant biology. In
      providing conduits for the exchange of small and large, informational molecules
      they are central to the growth, development and defence of all higher plants. In
      the past few years, strategies have been devised for the molecular dissection of
      plasmodesmal composition and function, and we are beginning to see how these
      enigmatic structures will become to be understood.

PMID- 18824403
TI  - Changes in intracortical circuits of the human motor cortex following theta burst
      stimulation of the lateral cerebellum.
AB  - OBJECTIVE: The cerebellum takes part in several motor functions through its
      influence on the motor cortex (M1). Here, we applied the theta burst stimulation
      (TBS) protocol, a novel form of repetitive Transcranial Magnetic Stimulation
      (rTMS) over the lateral cerebellum. The aim of this study was to test whether TBS
      of the lateral cerebellum could be able to modulate the excitability of the
      contralateral M1 in healthy subjects. METHODS: Motor-evoked potentials (MEPs)
      amplitude, short intracortical inhibition (SICI), long intracortical inhibition
      (LICI) and short intracortical facilitation (SICF) were tested in the M1 before
      and after cerebellar continuous TBS (cTBS) or intermittent TBS (iTBS). RESULTS:
      We found that cTBS induced a reduction of SICI and an increase of LICI. On the
      other hand, cerebellar iTBS reduced LICI. MEPs amplitude also differently vary
      following cerebellar stimulation with cTBS or iTBS, resulting in a decrease by
      the former and an increase by the latter. CONCLUSIONS: Although the
      interpretation of these data remains highly speculative, these findings reveal
      that the cerebellar cortex undergoes bidirectional plastic changes that modulate
      different intracortical circuits within the contralateral primary motor cortex.
      SIGNIFICANCE: Long-lasting modifications of these pathways could be useful to
      treat various pathological conditions characterized by an altered cortical
      excitability.

PMID- 18824404
TI  - Error and feedback processing in children with ADHD and children with Autistic
      Spectrum Disorder: an EEG event-related potential study.
AB  - OBJECTIVE: Performance monitoring was investigated in typically developing (TD)
      children, children with Autistic Spectrum Disorder (ASD), and Methylphenidate
      (Mph)-treated and medication-free children with Attention Deficit Hyperactivity
      Disorder (ADHD). METHODS: Subjects performed a feedback-based learning task.
      Event-related Potentials (ERPs) time locked to responses and feedback were
      derived from the EEG. RESULTS: Compared to the TD and ASD groups, the medication
      free ADHD group showed a decreased response-locked Error Related Negativity (ERN)
      and error Positivity (Pe), particularly as learning progressed throughout the
      task. Compared to the medication-free ADHD group, the Methylphenidate-treated
      group showed a normalised Pe. All clinical groups showed or tended to show a
      decreased feedback-locked late positive potential to negative feedback.
      CONCLUSIONS: The ERPs suggest that medication-free children with ADHD, but not
      with ASD, have a diminished capacity to monitor their error responses when they
      are learning by performance feedback. This capacity partially 'normalises' in Mph
      treated children with ADHD. Both children with ADHD and children with ASD are
      suggested being compromised in affective feedback processing. SIGNIFICANCE: This
      study shows that measuring ERPs of error and feedback processing is a useful
      method for (1) dissociating ADHD from ASD and (2) elucidating medication effects
      in ADHD on component processes of performance monitoring.

PMID- 18824405
TI  - Automated neonatal seizure detection mimicking a human observer reading EEG.
AB  - OBJECTIVE: The description and evaluation of a novel patient-independent seizure
      detection for the EEG of the newborn term infant. METHODS: We identified
      characteristics of neonatal seizures by which a human observer is able to detect
      them. Neonatal seizures were divided into two types. For each type, a fully
      automated detection algorithm was developed based on the identified human
      observer characteristics. The first algorithm analyzes the correlation between
      high-energetic segments of the EEG. The second detects increases in low-frequency
      activity (<8 Hz) with high autocorrelation. RESULTS: The complete algorithm was
      tested on multi-channel EEG recordings of 21 patients with and 5 patients without
      electrographic seizures, totaling 217 h of EEG. Sensitivity of the combined
      algorithms was found to be 88%, Positive Predictive Value (PPV) 75% and the false
      positive rate 0.66 per hour. CONCLUSIONS: Our approach to separate neonatal
      seizures into two types yields a high sensitivity combined with a good PPV and
      much lower false positive rate than previously published algorithms.
      SIGNIFICANCE: The proposed algorithm significantly improves neonatal seizure
      detection and monitoring.

PMID- 18824406
TI  - Brain-computer interfaces and communication in paralysis: extinction of goal
      directed thinking in completely paralysed patients?
AB  - OBJECTIVE: To investigate the relationship between physical impairment and brain
      computer interface (BCI) performance. METHOD: We present a meta-analysis of 29
      patients with amyotrophic lateral sclerosis and six patients with other severe
      neurological diseases in different stages of physical impairment who were trained
      with a BCI. In most cases voluntary regulation of slow cortical potentials has
      been used as input signal for BCI-control. More recently sensorimotor rhythms and
      the P300 event-related brain potential were recorded. RESULTS: A strong
      correlation has been found between physical impairment and BCI performance,
      indicating that performance worsens as impairment increases. Seven patients were
      in the complete locked-in state (CLIS) with no communication possible. After
      removal of these patients from the analysis, the relationship between physical
      impairment and BCI performance disappeared. The lack of a relation between
      physical impairment and BCI performance was confirmed when adding BCI data of
      patients from other BCI research groups. CONCLUSIONS: Basic communication
      (yes/no) was not restored in any of the CLIS patients with a BCI. Whether locked
      in patients can transfer learned brain control to the CLIS remains an open
      empirical question. SIGNIFICANCE: Voluntary brain regulation for communication is
      possible in all stages of paralysis except the CLIS.

PMID- 18824407
TI  - Dream life.

PMID- 18824408
TI  - Development of a Japanese version of the Epworth Sleepiness Scale (JESS) based on
      item response theory.
AB  - BACKGROUND: Various Japanese versions of the Epworth Sleepiness Scale (ESS) have
      been used, but none was developed via standard procedures. Here we report on the
      construction and testing of the developer-authorized Japanese version of the ESS
      (JESS). METHODS: Developing the JESS involved translations, back translations, a
      pilot study, and psychometric testing. We identified questions in the ESS that
      were difficult to answer or were inappropriate in Japan, proposed possible
      replacements for those questions, and tested them with analyses based on item
      response theory (IRT) and classical test theory. The subjects were healthy people
      and patients with narcolepsy, idiopathic hypersomnia, or obstructive sleep apnea
      syndrome. RESULTS: We identified two of our proposed questions as appropriate
      replacements for two problematic questions in the ESS. The JESS had very few
      missing data. Internal consistency reliability and test-retest reliability were
      high. The patients had significantly higher JESS scores than did the healthy
      people, and higher JESS scores were associated with worse daytime function, as
      measured with the Pittsburgh Sleep Quality Index. CONCLUSIONS: In Japan, the JESS
      provides reliable and valid information on daytime sleepiness. Researchers who
      use the ESS with other populations should combine their knowledge of local
      conditions with the results of psychometric tests.

PMID- 18824409
TI  - Chronobiology, excessive daytime sleepiness and depression: Is there a link?
AB  - The complaint of excessive daytime sleepiness (EDS), commonly encountered in
      clinical practice, may arise from a variety of psychiatric disorders, most
      importantly depression. Even though EDS frequently leads depressed patients to
      seek medical assistance, it is commonly under-evaluated and under-diagnosed.
      Therefore, a comprehensive understanding and management of EDS is essential in
      the clinical assessment of depression. Within a theoretical framework, a
      chronobiological approach may shed new light on the complex interaction of EDS
      and depression. In this review, studies on EDS and depression are summarized and
      discussed within the context of circadian and sleep regulatory mechanisms.
      Furthermore, potential chronobiological therapeutic strategies are proposed to
      address some of the unmet needs in the treatment of EDS and depression.

PMID- 18824410
TI  - The behavioural features of fatal familial insomnia: A new Italian case with
      pathological verification.
AB  - We report a new, pathologically verified Italian case of fatal familial insomnia,
      whose clinical presentation was characterised by complex behavioural
      disturbances, suggesting wakefulness/NREM/REM combinations.

PMID- 18824411
TI  - Undergraduate nursing students' level of assertiveness in Greece: a questionnaire
      survey.
AB  - BACKGROUND: A number of studies of nursing and midwifery have found stress and
      bullying to be frequent problems. Those suffering from bullying and stress need
      to have high levels of assertiveness to resist and to cope successfully. Hence,
      it was considered vital to assess the assertiveness level of nursing students
      throughout their training curriculum. METHODS: The study population was composed
      of nursing students in different semesters at one school in Central Greece
      (n=298) who agreed to complete a questionnaire on assertiveness level assessment,
      which had been translated into Greek and adapted to this population. All students
      present in class completed the questionnaire, representing 80% of the total
      population of active students. Mean assertiveness scores between semesters were
      compared by ANOVA and comparisons between the responses of the first semester
      students and responses of advanced semester students were done by Pearson's chi
      square. RESULTS: The main finding of this study was that the assertiveness levels
      displayed by students increase slightly in advanced semesters by comparison to
      those displayed by first-semester students. CONCLUSIONS: Assertive behavior
      should be encouraged through learning methods. Nurses should preferably obtain
      this training throughout their studies. Instructors have an essential role in the
      improvement and achievement of assertiveness training curriculums for
      undergraduate nursing students.

PMID- 18824412
TI  - Knowledge production and reproduction: what are the implications for nursing
      practice?
AB  - Research, teaching and practice are easy words to say and at first glance seem to
      be relatively simple to understand. The aim of research is to produce knowledge,
      teaching to reproduce it and practice to apply it. But a closer look at these
      terms reveals complex, competing, often contradictory sets of meanings which are
      embedded in differences in cultures, individuals and work practices. This paper
      examines some crucial issues surrounding ways of thinking about research,
      teaching and practice in nursing, drawing upon one of the stories in Homer's
      Odyssey as an organising framework. It argues for the importance of mentorship in
      navigating the multifaceted, intricate and personally confronting terrain that is
      nursing.

PMID- 18824413
TI  - Molecular characterization of Mycobacterium tuberculosis isolated in the State of
      Parana in southern Brazil.
AB  - Sequence IS6110 has been successfully used throughout the world for
      characterizing the Mycobacterium tuberculosis lineages. The aim of this study was
      to obtain data about circulating strains of M. tuberculosis in patients from the
      State of Parana in southern Brazil. Sixty-two clinical specimens obtained from
      sputum, bronchial aspirate, biopsy and urine from 62 patients clinically
      diagnosed with tuberculosis and admitted to the SUS-Brazil - The Brazilian
      Centralized Health Service System - were genotyped by the mixed-linker PCR DNA
      fingerprinting technique. The analysis demonstrated that the number of copies of
      the IS6110 sequence per isolates varied from four to 13 bands, with an average
      number of 8.5. From this, 93% of the isolates presented multiple copies. Isolates
      with no copies of the IS6110 element were not observed. The genetic analysis by
      UPGMA grouped the 62 isolates by similarity into three different groups: the
      first group contained two strains, the second was composed of 23, and the third,
      a more heterogeneous group, contained 37 isolates. Only two isolates (3.2%)
      formed a cluster; in other words, they presented a pattern of polymorphism with
      similarity above 95%. Such findings suggest that in the State of Parana, illness
      predominantly develops through reactivation of the latent infection as opposed to
      exogenous transmission. The methodology used (mixed-linker PCR DNA
      fingerprinting) allowed for 93.5% differentiation of the isolates tested, and
      proved to be a powerful tool for differentiation in the molecular genotyping of
      M. tuberculosis.

PMID- 18824414
TI  - Functional impairment in circulating and intrahepatic NK cells and relative
      mechanism in hepatocellular carcinoma patients.
AB  - Functional defects in natural killer (NK) cells have been proposed to be
      responsible for the failure of anti-tumor immune responses. Whether and how NK
      cells are impaired in hepatocellular carcinoma (HCC) patients remain unknown. In
      this study, we found that HCC patients displayed a dramatic reduction in
      peripheral CD56(dim)CD16(pos) NK subsets compared with healthy subjects. A
      significant reduction of CD56(dim)CD16(pos) NK subsets was also found in tumor
      regions compared with non-tumor regions in the livers of these HCC patients. Both
      these peripheral and tumor-infiltrating NK cells exhibited poorer capacity to
      produce IFN-gamma and kill K562 targets, which was further found to be associated
      with increased CD4(+)CD25(+) T regulatory cells as we previously-described in HCC
      patients. Addition of Tregs from HCC patients efficiently inhibited the anti
      tumor ability of autologous NK cells in vitro. These findings are helpful for
      understanding the mechanism of NK cell-mediated anti-tumor immune responses in
      HCC patients.

PMID- 18824415
TI  - Endothelial permeability is controlled by spatially defined cytoskeletal
      mechanics: atomic force microscopy force mapping of pulmonary endothelial
      monolayer.
AB  - Actomyosin contraction directly regulates endothelial cell (EC) permeability, but
      intracellular redistribution of cytoskeletal tension associated with EC
      permeability is poorly understood. We used atomic force microscopy (AFM), EC
      permeability assays, and fluorescence microscopy to link barrier regulation, cell
      remodeling, and cytoskeletal mechanical properties in EC treated with barrier
      protective as well as barrier-disruptive agonists. Thrombin, vascular endothelial
      growth factor, and hydrogen peroxide increased EC permeability, disrupted cell
      junctions, and induced stress fiber formation. Oxidized 1-palmitoyl-2
      arachidonoyl-sn-glycero-3-phosphocholine, hepatocyte growth factor, and iloprost
      tightened EC barriers, enhanced peripheral actin cytoskeleton and adherens
      junctions, and abolished thrombin-induced permeability and EC remodeling. AFM
      force mapping and imaging showed differential distribution of cell stiffness:
      barrier-disruptive agonists increased stiffness in the central region, and
      barrier-protective agents decreased stiffness in the center and increased it at
      the periphery. Attenuation of thrombin-induced permeability correlates well with
      stiffness changes from the cell center to periphery. These results directly link
      for the first time the patterns of cell stiffness with specific EC permeability
      responses.

PMID- 18824416
TI  - In vivo studies of polyacrylate nanoparticle emulsions for topical and systemic
      applications.
AB  - We have recently reported on a new nanomedicine containing antibiotic-conjugated
      polyacrylate nanoparticles, which has shown activity against methicillin
      resistant Staphylococcus aureus (MRSA) in vitro and no cytotoxicity toward human
      dermal cells. The water-based nanoparticle emulsion is capable of solubilizing
      lipophilic antibiotics for systemic administration, and the nanoparticle drug
      delivery vehicle has shown protective properties for antibiotics from hydrolytic
      cleavage by bacterial penicillinases, thus rejuvenating the drug's activity
      against resistant microbes such as MRSA. Here we report the first in vivo study
      of this penicillin-conjugated nanoparticle emulsion in determining toxicological
      responses initiated upon systemic and topical application in a murine model.
      Favorable results were observed in vivo upon both routes of administration and,
      when topically applied to a dermal abrasion model, the emulsion enhanced wound
      healing by an average of 3 to 5 days. This study suggests that polyacrylate
      nanoparticle-containing emulsions may afford promising opportunities for treating
      both skin and systemic infections.

PMID- 18824417
TI  - Morphological and quantitative study of ganglionated plexus of Calomys callosus
      trachea.
AB  - Calomys callosus is a wild, native forest rodent found in South America. In
      Brazil, this species has been reported to harbour the parasitic protozoan
      Trypanosoma cruzi. The ganglionated plexus of this species was studied using
      whole-mount preparations of trachea that were stained using histological and
      histochemical methods. The histological methods were used to determine the
      position of the ganglia with respect to the trachea muscle and to determine the
      presence of elastic and collagen fibers. The histochemical method of NADH
      diaphorase was used for morphometric evaluations of the plexus. The tracheal
      plexus lies exclusively over the muscular part of the organ, dorsal to the muscle
      itself. It varies in pattern and extent between animals. The average number of
      neurons was 279 and the cellular profile area ranged from 38.37 microm2 to 805.89
      microm2. Acetylcholinesterase (AChE) histochemistry verified that both ganglia
      and single neurons lie along nerve trunks and are reciprocally interconnected
      with the plexus. Intensely AChE-reactive neurons were found to be intermingled
      with poorly reactive ones. Two longitudinal AChE-positive nerve trunks were also
      observed and there was a diverse number of ganglia along the intricate network of
      nerves interconnecting the trunks. A ganglion capsule of collagen and elastic
      fibers surrounding the neurons was observed. Under polarized light, the capsule
      appeared to be formed by Type I collagen fibers.

PMID- 18824418
TI  - Extracting kinetic parameters for homogeneous [Os(bpy)2ClPyCOOH]+ mediated enzyme
      reactions from cyclic voltammetry and simulations.
AB  - The homogeneous reaction between glucose oxidase and osmium bipyridine-pyridine
      carboxylic acid in the presence of glucose has been studied in detail by cyclic
      voltammetry and digital simulation. Combination of the analytical equations that
      describe the dependence of the amperometric response on enzyme, substrate and co
      substrate concentrations for the limiting cases with digital simulation of the
      coupled enzyme reaction diffusion problem allows us to extract kinetic parameters
      for the substrate-enzyme reaction: K(MS)=10.8 mM, k(cat)=254 s(-1) and for the
      redox mediator-enzyme reaction, k=2.2x10(5) M(-1) s(-1). The accurate
      determination of the kinetic parameters at low substrate concentrations (<7 mM)
      is limited by depletion of the substrate close to the electrode surface. At high
      substrate concentrations (>20 mM) inactivation of the reduced form of glucose
      oxidase in the bulk solution must be taken into account in the analysis of the
      results.

PMID- 18824419
TI  - Sensitive and selective liquid chromatography/tandem mass spectrometry methods
      for quantitative analysis of 1-methyl-4-phenyl pyridinium (MPP+) in mouse
      striatal tissue.
AB  - The systemic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
      (MPTP) to mice produces a reliable and selective degeneration of the
      nigrostriatal pathway, a hallmark feature of Parkinson's disease (PD).
      Determining the brain concentrations of 1-methyl-4-phenyl pyridium (MPP+), the
      neurotoxic metabolite of MPTP, is critical for evaluating drugs designed to
      potentially treat PD. We have developed sensitive and specific quantitative
      methods for the determination of MPP+ in mouse striatal tissue by liquid
      chromatography/tandem mass spectrometry. The separations were carried out based
      on reversed phase chromatography or cation exchange chromatography with volatile
      elution buffer. Neutralizing the brain sample with 0.2M phosphate buffer
      successfully solved a high-performance liquid chromatography (HPLC) peak tailing
      of MPP+ in brain extracts with 0.4M perchloric acid (HClO4) under the reversed
      phase HPLC conditions, which significantly improved the sensitivity of the
      method. The HPLC peak shape of MPP+ using cation exchange chromatography was not
      affected by the pH of the samples. Optimization of electrospray ionization (ESI)
      conditions for the quaternary ammonium compound MPP+ established the limits of
      detection (LOD) (S/N=3) at 0.34pg/mg tissue and 0.007pg/mg tissue (5microl of
      injection) using the reversed phase liquid chromatography/tandem mass
      spectrometry (LC/MS/MS) and the cation exchange LC/MS/MS, respectively. Both
      methods were selective, precise (%R.S.D.<6%), and sensitive over a range of 0.001
      1ng/mg tissue. The cation exchange method showed greater sensitivity and
      tolerance to low pH samples than the reversed phase method. The developed methods
      were applied to monitoring changes in MPP+ concentrations in vivo. Two reference
      agents, R-(-) Deprenyl and MK-801, known to alter the concentration of MPP+ in
      MPTP treated mice were evaluated.

PMID- 18824420
TI  - Assessment of caspase-4 released free AFC by RP-HPLC and fluorescence detection.
AB  - A simple RP-HPLC method based on fluorescence detection was developed for the
      quantitation of 7-amino-4-trifluoro methylcoumarin (AFC) in cell lysates from JEG
      3 choriocarcinoma cells for determination of caspase-4 activity. In contrast to
      the established methods of AFC detection using a fluorescence microplate reader
      or using a fluorescence photometer, the separation of AFC-signals from
      interfering fluorescence signals by a reversed phase column affords more precise
      quantitation of released AFC. This can be important for analyses of cell lysates
      with low caspase activity or experimental series with marginal differences among
      samples. By applying this new method, a linear dynamic range of 40pmol/mL to
      3nmol/mL with a correlation coefficient of 0.9996 was achieved. Due to the short
      retention time ( approximately 7min), the determination of AFC by RP-HPLC under
      isocratic conditions requires small amounts of samples (50microL injection
      volume), and allows increased sample throughput. This method should be easily
      applied with little or no modification to other caspase assays by using the same
      fluorophore.

PMID- 18824421
TI  - Fabrication of three-dimensional cartilaginous framework in auricular
      reconstruction.
AB  - OBJECTIVE: One of the greatest challenges in facial plastic surgery is total
      auricular reconstruction, as it demands precise technique as well as artistic
      creativity. The crucial step to reconstruct satisfactory auricles is sculpting a
      three-dimensional cartilaginous framework, which determines the success of
      surgery. In this paper we describe our new techniques in fabricating the three
      dimensional auricular framework. METHODS: To assemble satisfactory auricular
      frameworks, we designed four different methods according to the number of rib
      cartilages used. (1) Method I, the framework was made from the entire 6th, 7th
      and 8th rib cartilages; (2) method II, the framework was made from the partial
      6th, the entire 7th and 8th rib cartilages; (3) method III, the framework was
      made from the entire 7th and 8th rib cartilages; (4) method IV, the framework was
      made only from the entire 7th rib cartilage. RESULTS: 332 patients, ranging in
      age from 5 to 33 years old, were operated on using autogenous costal cartilage
      between 2004 and 2006. All the reconstructed ears had a satisfactory three
      dimensional configuration. The cranioauricular angle of the reconstructed ears
      was also similar to that of the opposite ears. CONCLUSIONS: According to the
      status of the normal ear and the development of the cartilage in each patient, we
      have developed four methods to harvest and fabricate cartilage. Our operations on
      332 patients with microtia suggest that our new technique is effective in
      fabricating cartilaginous framework. Our new technique facilitates the operation
      procedure and minimises the usage of cartilage.

PMID- 18824422
TI  - Student's Corner.
AB  - An undergraduate student at Rensselaer Polytechnic Institute has learned very
      quickly that a spoonful of sugar really does help the medicine go down. In fact,
      with his invention, the sugar may actually be the medicine!

PMID- 18824423
TI  - Diffusion-weighted magnetic resonance imaging in neck lymph adenopathy.
AB  - In patients with head and neck squamous cell carcinoma (SCC), nodal metastases
      are an adverse prognostic factor compromising long term patient survival.
      Therefore, accurate detection of regional nodal metastases is required for
      optimization of treatment. Computed tomography (CT) and magnetic resonance
      imaging (MRI) remain the primary imaging modalities for locoregional staging of
      head and neck SCC. Next to evaluation of the primary tumour, both modalities
      facilitate detection of non-palpable lymph nodes (LN). However, both modalities
      rely on size-related and morphological criteria to differentiate between benign
      and malignant lymph nodes, decreasing the sensitivity for detection of small
      metastases. Diffusion-weighted MRI (DW-MRI) measures differences in tissue
      microstructure, based on the random displacement of water molecules. The
      differences in water mobility are quantified using the apparent diffusion
      coefficient (ADC), which has an inverse relationship with tissue cellularity. As
      such the technique is able to differentiate between tumoral tissue and normal or
      necrotic tissue. The added value of DW-MRI to conventional imaging for staging of
      lymph nodes in head and neck cancer is discussed, before and after treatment. The
      possible consequences regarding therapeutic management are outlined.

PMID- 18824424
TI  - Non-small cell lung cancer staging: proposed revisions to the TNM system.
AB  - Patients with non-small cell lung cancer (NSCLC) require careful staging at the
      time of diagnosis to determine prognosis and guide treatment recommendations. The
      seventh edition of the TNM Classification of Malignant Tumors is scheduled to be
      published in 2009 and the International Association for the Study of Lung Cancer
      (IASLC) created the Lung Cancer Staging Project (LCSP) to guide revisions to the
      current lung cancer staging system. These recommendations will be submitted to
      the American Joint Committee on Cancer (AJCC) and to the Union Internationale
      Contre le Cancer (UICC) for consideration in the upcoming edition of the staging
      manual. Data from over 100,000 patients with lung cancer were submitted for
      analysis and several modifications were suggested for the T descriptors and the M
      descriptors although the current N descriptors remain unchanged. These
      recommendations will further define homogeneous patient subsets with similar
      survival rates. More importantly, these revisions will help guide clinicians in
      making optimal, stage-specific, treatment recommendations.

PMID- 18824426
TI  - Decision-making in clinically localized prostate cancer: evaluating and
      communicating risks.

PMID- 18824427
TI  - Highlights from: The 2008 meeting of the American Society of Clinical Oncology;
      May 30-June 3, 2008; Chicago, IL.

PMID- 18824428
TI  - Motexafin gadolinium for the treatment of metastatic renal cell carcinoma: phase
      II study results.
AB  - BACKGROUND: Thioredoxin reductase (Trx) has been implicated in activation of
      hypoxia-inducible factor-1alpha, which is overexpressed in > 85% of renal cell
      carcinomas (RCCs). We evaluated the safety and efficacy of motexafin gadolinium
      (MGd), a Trx inhibitor, as a single-agent therapy for metastatic RCC. PATIENTS
      AND METHODS: Patients with metastatic RCC were infused daily with MGd 5 mg/kg on
      days 1-5 and days 15-19 of each 28-day cycle. Patients were evaluated for
      response on days 21-28 of every third cycle. Those with tumor response or stable
      disease (SD) continued treatment for < or = 12 cycles. Twenty-five patients with
      confirmed metastatic RCC were enrolled. All were evaluable for toxicity, and 20
      were evaluable for response. RESULTS: While no clinical responses were observed,
      8 patients had SD after 3 treatment cycles, as did 4 after 6 cycles. Median
      overall survival was 10.1 months, and median progression- free survival was 2.7
      months. The most common treatment-related toxicities were grade 1/2 pain, nausea,
      skin discoloration, fatigue, blisters, and headache. The most common grade 3
      toxicity was hypophosphatemia, observed in 5 patients. MGd was reasonably
      tolerated, and disease stabilization was observed in several patients with
      metastatic RCC. CONCLUSION: These results show promise for the use of MGd in
      combination with other molecularly targeted therapies in previously treated
      patients with metastatic RCC. However, further investigation of MGd alone for
      metastatic RCC is not recommended.

PMID- 18824429
TI  - Phase I/II trial of 5-fluorouracil and a noncytotoxic dose level of suramin in
      patients with metastatic renal cell carcinoma.
AB  - BACKGROUND: Renal cell carcinoma (RCC) is recognized as a neoplasm resistant to
      chemotherapy. In vitro experiments demonstrated that suramin, at noncytotoxic
      doses, enhanced the activity of chemotherapy including 5-fluorouracil (5-FU) in
      xenograft models. PATIENTS AND METHODS: A phase I/II trial of noncytotoxic
      suramin in combination with weekly 5-FU in patients with metastatic RCC was
      conducted. The treatment consisted of intravenous (i.v.) suramin followed by a
      500 mg/m2 i.v. bolus of 5-FU given 4.5 hours after starting suramin. In the phase
      I portion, a cohort of 6 patients received a suramin dose calculated to achieve a
      plasma level of 10-50 micromol/L. Therapy was administered once weekly for 6
      doses, followed by 2 weeks off. This was followed by a phase II portion in which
      the primary goal was to determine the objective response rate. RESULTS: Twenty
      three patients were enrolled in the study: 6 in the phase I portion and 17 in
      phase II. Seventy-eight percent of patients were men, the mean age was 58.8
      years, 96% had previous nephrectomy, and 70% had received previous systemic
      therapy. Histologic subtype was clear cell in 91%. Dose-limiting toxicity was
      observed in 1 of 6 patients (grade 3 hypersensitivity related to suramin
      infusion). The suramin dosing nomogram used in phase I and II portions of the
      trial yielded the desired plasma level of 10-50 micromol/L from 4.5 hours to 48
      hours after infusion in 94 of 115 treatments. No objective responses were noted,
      and the median time to treatment failure was 2.5 months. The major toxicities
      (all grades) were fatigue (83%), nausea/vomiting (78%), diarrhea (61%), and
      chills (61%). CONCLUSION: Suramin levels expected to reverse fibroblast growth
      factor-induced resistance can be achieved with the dosing regimen used in this
      study. The toxicity observed with suramin and 5-FU was acceptable. The
      combination does not have clinical activity in patients with metastatic RCC.

PMID- 18824430
TI  - Human immunodeficiency virus--associated renal cell carcinoma: a transatlantic
      case series.
AB  - OBJECTIVE: The spectrum of diseases associated with human immunodeficiency virus
      (HIV) infection has changed dramatically following the introduction of highly
      active antiretroviral therapy (HAART). Non-AIDS-defining cancers, including renal
      cell carcinoma (RCC), are being recognized increasingly in this population. Our
      aim was to describe the risk factors, clinical findings, pathology, and response
      to therapy of RCC in patients infected with HIV. PATIENTS AND METHODS: We
      identified 9 men with HIV infection who developed RCC. Data regarding their HIV
      status, RCC risk factors, clinical presentation, and pathology were collected. A
      detailed retrospective chart review focusing on the course of their malignancy,
      response to therapy, and outcome was performed. RESULTS: Renal cell carcinoma was
      diagnosed in patients with a median age of 48 years, and most had a history of
      tobacco use. No association between HIV-related immunosuppression (mean CD4
      count, 301 cells/mm3) and the development, clinical presentation, pathology, or
      behavior of RCC was identified. Long-term survival correlated with early
      nephrectomy, and the use of interleukin-2 therapy for advanced RCC was not
      additive. A total of 5 patients died, 1 from a pulmonary embolism and 4 from
      disseminated RCC. CONCLUSION: Renal cell carcinoma should be included in the
      expanding array of non-AIDS-defining malignancies that develop during the course
      of HIV infection. Acknowledging the inherent limitations of our small study,
      these data show that the clinical presentation and behavior of RCC in patients
      with HIV appear similar to that of the HIV-negative population and that chronic
      immunosuppression plays a lesser role than age and exposure to risk factors in
      this setting.

PMID- 18824431
TI  - Patient satisfaction with health-related quality of life: implications for
      prognosis in prostate cancer.
AB  - PURPOSE: The goal of this study was to evaluate the association between patient
      satisfaction with health-related quality of life (HRQOL), as measured by the
      Ferrans and Powers Quality of Life Index (QLI), and survival in patients with
      prostate cancer treated in an integrative cancer treatment setting. MATERIALS AND
      METHODS: This is a case series of 230 histologically confirmed stage I-IV
      prostate cancers treated at Cancer Treatment Centers of America. Quality of Life
      Index measures overall HRQOL and HRQOL in 4 major subscales: health and physical,
      social and economic, psychological and spiritual, and family. Study patients were
      dichotomized into 2 groups based on the median scores for all QLI subscales.
      Kaplan- Meier and log-rank tests were used to evaluate survival. Multivariate Cox
      regression analyses were then performed to evaluate the joint prognostic
      significance of HRQOL and clinical factors. RESULTS: Patient satisfaction with
      health and physical (P = .0001), psychological and spiritual (P = .03), family (P
      = .02), and overall HRQOL (P = .0001) were statistically significantly associated
      with survival upon univariate analysis. Upon multivariate analysis, patient
      satisfaction with the health and physical subscale was found to be predictive of
      survival (P = .04), independent of the effects of previous treatment history and
      Gleason score. CONCLUSION: This study suggests that baseline patient satisfaction
      with health and physical function, as measured by the QLI, provides useful
      prognostic information in patients with prostate cancer, independent of previous
      treatment history and Gleason score. The QLI Index can be used as a
      stratification variable in the oncology clinic to aid in medical decision-making.

PMID- 18824432
TI  - Pilot study of rapamycin in patients with hormone-refractory prostate cancer.
AB  - BACKGROUND: Currently, no second-line treatment exists for hormonerefractory
      prostate cancer (HRPC) cases that fail docetaxel regimens. Rapamycin, an
      immunosuppressive macrolide, inhibits metastatic prostate tumor growth and
      angiogenesis in in vivo mouse models. This pilot study assessed the antitumor
      activity, safety, and toxicity of rapamycin in patients with HRPC. PATIENTS AND
      METHODS: Eligible patients had HRPC and disease progression. The initial dose of
      rapamycin was 0.15 mg/kg followed by 0.04 mg/kg daily without interruption.
      Rapamycin levels were measured every 28 days with dose adjustments of 0.04-0.06
      mg/kg as necessary to maintain levels between 6-10 ng/mL. Patients were evaluated
      every 4 weeks for prostate-specific antigen (PSA) and safety and every 8 weeks
      for radiographic response. RESULTS: Thirteen patients were enrolled from January
      2005 to February 2006. One was not evaluable for response. Responses were seen in
      2 of 12 evaluable patients (17%). One patient experienced a 50% decrease in
      absolute PSA and partial radiographic response; another experienced a PSA
      response only. Four patients had stable disease (33%). The median progression
      free survival was 4.2 months (range, 1.9-23.3 months), and overall survival was
      23.3+ months (range, 1.9-34.3+ months). Diarrhea (69%), fatigue (46%), and nausea
      (46%) were the most common adverse events. Rapamycin was well tolerated and
      showed signs of antitumor activity. CONCLUSION: Rapamycin and other inhibitors of
      mammalian targets of rapamycin warrant further study in developing combination
      therapies with chemotherapy or radiation.

PMID- 18824433
TI  - Southwest Oncology Group phase II study of ispinesib in androgen-independent
      prostate cancer previously treated with taxanes.
AB  - PURPOSE: The mitotic spindle has proven to be an effective therapeutic target in
      antineoplastic efforts. In this study, we sought to assess the efficacy of
      ispinesib, a mitotic kinesin spindle protein (KSP) inhibitor in androgen
      independent prostate cancer progressing after docetaxel. PATIENTS AND METHODS:
      Patients were treated with ispinesib 18 mg/m2 every 21 days and assessed for
      prostate-specific antigen (PSA) and measurable disease response at regular
      intervals. Kinesin spindle protein expression in archival tumors, population
      ispinesib pharmacokinetics, and pharmacodynamic assessments of circulating
      lymphocytes were included. RESULTS: The study was terminated after first stage
      because no responses were seen in the first 21 patients. Median duration of PSA
      or clinical progression-free survival was 9 weeks. Plasma concentrations of
      ispinesib were comparable with those observed in previous phase I investigations.
      Immunohistochemical analysis of archival tumor specimens did not demonstrate
      significant KSP expression in most of the prostate cancer cases studied.
      Pharmacodynamic assessments of circulating lymphocytes from patients receiving
      ispinesib showed an absence of monopolar spindle formation, as would be expected
      if the drug were having its expected effects. CONCLUSION: Ispinesib was inactive
      in this study of patients with androgen-independent, and largely
      docetaxelresistant, prostate cancer. The lack of efficacy might be explained by
      the low expression of the drug target seen in prostate cancer, whereas not
      detecting monopolar spindles in circulating lymphocytes with drug treatment
      likely reflects the lack of dividing cells in peripheral blood.

PMID- 18824434
TI  - A phase II study of estramustine, docetaxel, and exisulind in patients with
      hormone- refractory prostate cancer: results of cancer and leukemia group B trial
      90004.
AB  - PURPOSE: Docetaxel/estramustine is a known active regimen in hormonerefractory
      prostate cancer (HRPC). A phase II study was conducted to assess the safety and
      efficacy of docetaxel/estramustine combined with exisulind, an apoptotic
      antineoplastic drug. PATIENTS AND METHODS: Eighty men with chemotherapy-naive
      HRPC were enrolled in a multicenter, cooperative group study. The treatment
      regimen consisted of oral estramustine (280 mg 3 times daily for 5 days),
      docetaxel 70 mg/m2, oral exisulind (250 mg twice daily), oral dexamethasone (8 mg
      twice daily for 3 days), and oral warfarin (2 mg daily). RESULTS: Seventy-five
      eligible patients were treated with a median of 6 cycles of therapy. Fortyseven
      patients (62.7%; 95% CI, 50.7%-73.6%) had a > or = 50% decline in prostate
      specific antigen levels. Forty-six patients had measurable disease with 6 partial
      responses (13%; 95% CI, 4.9%-26.3%). The main grade 3/4 toxicities were
      neutrophils (79%), fatigue (15%), and thrombosis/embolism (10%). The median time
      to first progression was 5.1 months (95% CI, 4.4-6.3 months) and the median
      survival time was 17.8 months (95% CI, 14.7-20.1 months). CONCLUSION: The
      combination of estramustine/docetaxel/exisulind was associated with significant
      thomboembolic toxicity despite prophylactic warfarin. The contribution of
      exisulind to toxicity is uncertain. Prostate-specific antigen decline, response
      rates, and progression-free and overall survival are similar to those reported
      with docetaxel/estramustine.

PMID- 18824436
TI  - Sunitinib-induced acute hemolysis without hypertension: a case report.
AB  - Sunitinib-associated hematologic adverse events are well known and include
      leukopenia, neutropenia, thrombocytopenia, anemia, and lymphopenia. Herein, we
      report the case of a patient with metastatic renal cell carcinoma who was treated
      with sunitinib and developed severe hemolysis without hypertension or reversible
      posterior leukoencephalopathy. Prompt discontinuation of the agent resulted in
      resolution of this complication.

PMID- 18824435
TI  - Bax-interacting factor-1 expression in prostate cancer.
AB  - BACKGROUND: Bax-interacting factor (Bif)-1 protein is a member of the endophilin
      B family that binds to and activates the proapoptotic Bax protein in response to
      apoptotic signals. Loss of Bif-1 suppresses the intrinsic pathway of apoptosis
      and promotes tumorigenesis. We examined the expression levels of Bif-1 protein in
      human prostate cancer. MATERIALS AND METHODS: Thirty-nine archival tissue
      specimens of human prostate cancer, and a human prostate cancer tissue microarray
      containing 19 samples of normal prostate, 26 samples of benign prostatic
      hyperplasias (BPHs), 30 samples of high-grade prostatic intraepithelial neoplasia
      (PIN), and 153 samples of prostate cancer, were selected for immunohistochemical
      staining with Bif-1 antibody. The slides were scored by 2 independent observers.
      RESULTS: Nontissue microarray samples: moderate to strong Bif-1 staining was
      identified in 38 of 39 prostate cancer samples. In 32 cases, foci of PIN were
      identified adjacent to prostate cancer samples. Of these, 29 samples (90.6%)
      showed strong and diffuse Bif-1 staining. Benign prostatic hyperplasias,
      identified in 27 cases, was weakly Bif-1 positive in 88.9% of cases. Tissue
      microarray samples: 38.6% (59 of 153) of prostate cancer samples showed moderate
      to strong Bif-1 expression, and 21.6% (33 of 153) were Bif-1 negative. Bif-1
      expression was moderate to strong in 76.7% (23 of 30) of PIN. Bif-1 was weak to
      moderate in 53.8% (14 of 26) of BPH and negative in 46.2% (12 of 26) of them. Low
      to moderate Bif-1 was seen in 89.5% of normal prostate samples. CONCLUSION: The
      loss of Bif-1 expression in a subset of prostate cancer samples is in agreement
      with the proapoptotic function of Bif-1. The significance of the increased Bif-1
      in a subgroup of prostate cancer samples and in PIN remains to be determined. It
      seems that Bif-1 has a role in prostate cancer, providing the rationale for using
      Bif-1 as a target for prostate anticancer therapy.

PMID- 18824437
TI  - Nephrectomy in the management of metastatic osteosarcoma.
AB  - This report discusses a rare case of nephrectomy for metastatic osteosarcoma, the
      first performed laparoscopically, and proposes such management as a standard of
      care. A 21-year-old woman with a history of metastatic osteosarcoma involving her
      right kidney was referred to our institution for evaluation. She was managed with
      a hand-assisted laparoscopic nephrectomy. An exhaustive review of the English
      literature pertaining to this disease was performed. To our knowledge, this case
      represents only the sixth nephrectomy ever reported for metastatic osteosarcoma
      and the first performed by a laparoscopic approach. In addition, this is the
      first reported case of this disease invading the renal vein. The literature
      suggests that the incidence of renal involvement in osteosarcoma is significant
      and that renal imaging should be mandatory in such patients. When renal
      metastases are diagnosed, prompt nephrectomy is warranted. A minimally invasive
      approach in these patients should be considered.

PMID- 18824438
TI  - Multisystem crisis in a patient with presumptive renal cell carcinoma.
AB  - We describe the case of a patient who presented with a kidney lesion,
      lymphadenopathy, and bone metastasis. He developed a tetrad of high fever,
      encephalopathy, labile blood pressure, and multiple organ system failure.
      Initially, he was diagnosed with metastatic renal cell carcinoma (RCC). His
      fevers and encephalopathy were compatible with a putative paraneoplastic
      syndrome. Eventually, he was found to have malignant pheochromocytoma. To our
      knowledge, this is the first reported case of a malignant pheochromocytoma with
      multisystem crisis. Because of its atypical presentation and unusual findings, a
      high index of suspicion is necessary for the timely diagnosis of this clinical
      entity. Prompt diagnosis and appropriate treatments could improve the performance
      status and quality of life of such patients.

PMID- 18824439
TI  - Primary clear-cell adenocarcinoma of the proximal female urethra: case report and
      review of the literature.
AB  - Primary carcinoma of the female urethra is a rare entity. Adenocarcinomas account
      for only 10% of cases. Clear cell adenocarcinoma (CCA) of the urethra is more
      common among women than men.1 We report a case of primary CCA of the urethra and
      review the literature concerning the histogenesis, management, and outcome of
      this uncommon tumor.

PMID- 18824440
TI  - Phase II trial of sunitinib for the therapy of progressive metastatic castration
      refractory prostate cancer after previous docetaxel chemotherapy.
AB  - Effective options are lacking for progressive castration-refractory prostate
      cancer (CRPC) after conventional chemotherapy. Sunitinib is an orally
      administered multitargeted tyrosine kinase inhibitor that is approved
      multinationally for renal cell carcinoma and gastrointestinal stromal tumors. A
      phase II trial was conducted to examine the efficacy and toxicities of sunitinib
      in metastatic CRPC progressing after 1-2 previous chemotherapy regimens including
      docetaxel. The primary objective was clinical progression-free survival (PFS)
      with a 12-week PFS > or = 30% assumed to be of interest. Secondary objectives
      included prostate-specific antigen (PSA) response, modulation of PSA kinetics,
      objective response, quality of life, pain, survival, and toxicities. Sunitinib 50
      mg daily was administered orally on days 1-28 of each 6-week cycle. Patients were
      treated to a maximum of 8 cycles or until clinically progressive disease or
      intolerable toxicity.

PMID- 18824445
TI  - Will FLEX allow us flexibility in the therapy of advanced non-small-cell lung
      cancer? Insights from the 2008 American Society of Clinical Oncology Meeting.

PMID- 18824446
TI  - Small cell, big problem! Stem cells, root cause?

PMID- 18824448
TI  - Primary pleuropulmonary synovial sarcoma.
AB  - Pleuropulmonary synovial sarcoma (PPSS) is increasingly recognized as a subtype
      of sarcoma because of the recent identification of a distinctive chromosomal
      translocation specific to synovial sarcoma. Soft-tissue synovial sarcoma is far
      more common than PPSS and typically develops in para-articular locations of the
      extremities, affects young and middle-aged adults, with no difference in
      distribution between the sexes, and has well-documented radiologic
      manifestations. Pleuropulmonary synovial sarcoma can arise in the chest wall,
      heart, mediastinum, pleura, or lung, and it shares patient demographics and
      several imaging features with its soft-tissue counterpart. Patients present with
      a cough, chest pain, or dyspnea. On chest radiographs, PPSS typically appears as
      a sharply marginated mass with uniform opacity, based in the pleura or in the
      lung, and often accompanied by an ipsilateral pleural effusion. Computed
      tomographic images show a well-circumscribed, heterogeneously enhanced lesion
      without associated involvement of bone and without calcifications (except in the
      case of a chest wall primary tumor). Magnetic resonance imaging provides superior
      demonstration of nodular soft tissue and multilocular fluid-filled internal
      components of PPSS, in addition to peripheral rim enhancement after the
      intravenous administration of a gadoliniumbased contrast material such as
      gadopentetate dimeglumine. Current treatment consists of surgical resection
      followed by chemotherapy, radiation therapy, or both.

PMID- 18824449
TI  - New targeted therapies and small-cell lung cancer.
AB  - Small-cell lung cancer (SCLC) accounts for almost 15% of lung carcinomas.
      Chemotherapy is the cornerstone of treatment of patients with SCLC. In limited
      disease, median survival is about 12-20 months, with no more than 6%-12% of
      patients surviving beyond 5 years. In extensive disease, median survival is 7-12
      months, with < 5% of patients living beyond 2 years and a 5-year survival rate of
      just 2%. Several therapeutic approaches have been used in an attempt to improve
      the outcome of SCLC. Among these, a better understanding of tumor biology and the
      subsequent development of novel therapeutic strategies have been identified as a
      possible approach for increasing the survival rate of patients with SCLC. Several
      targeted agents have been introduced into clinical trials in SCLC, and a few
      phase III studies, including matrix metalloproteinase inhibitors, thalidomide,
      and vaccines, have already produced definitive results. Currently, negative
      results are more commonly reported than positive ones. However, this first
      generation of clinical trials represents only the beginning of clinical research
      in this field. To date, no targeted therapy has been approved for use in the
      treatment of patients with SCLC. Nevertheless, clinical research in this field is
      still in progress considering that several new targeted agents, such as
      antiangiogenic agents and mammalian target of rapamycin inhibitors, offer a
      promise of improved outcomes. This review will focus on the reported results and
      the future development of the main novel biologic agents for the treatment of
      patients with SCLC.

PMID- 18824450
TI  - Weekly paclitaxel in elderly patients (aged > or = 70 years) with advanced non
      small-cell lung cancer: an alternative choice? Results of a phase II study.
AB  - PURPOSE: Paclitaxel and platinum-based chemotherapy is considered to be a
      standard approach for locally advanced and metastatic non-small-cell lung cancer
      (NSCLC). In recent years, weekly paclitaxel has been widely used for its safety
      profile, especially in breast and ovarian cancer. Otherwise, only a few studies
      are available in NSCLC. The aim of our study was to investigate the activity and
      safety of weekly paclitaxel in elderly patients with locally advanced (stage
      IIIB) and metastatic (stage IV) NSCLC. PATIENTS AND METHODS: Twenty-seven
      patients entered the study; 10 had stage IIIB disease (5 "wet" and 5 "dry"), and
      17 had stage IV disease. Median age was 73 years (range, 70-83 years). Sixteen
      patients (59%) presented with comorbidities. The schedule was weekly paclitaxel
      80 mg/m2 for 6 weeks with 2 weeks of rest (1 cycle). RESULTS: All patients were
      evaluable for response and toxicity; a median of 1 cycle was administered (range,
      1-5 cycles). Partial responses were recorded in 9 patients (37.5%; 33.3%,
      according to intention-to- treat analysis; 95% CI, 15.5%-51.1%); 7 had stable
      disease (29%), and 8 had progressive disease (33.5%). Median time to progression
      was 5 months (range, 1-23 months), and median survival was 12 months (range, 1-36
      months). Grade 2/3 asthenia was the main toxicity in 7 patients (29%); a
      hypersensitivity reaction presented in 1 patient. No other episode of grade 3/4
      toxicity was recorded. CONCLUSION: Our study confirmed that paclitaxel 80 mg/m2
      weekly is active in patients with locally advanced and metastatic NSCLC with a
      good safety profile; this schedule might be considered an alternative choice to
      gemcitabine or vinorelbine as first-line treatment in elderly patients,
      particularly patients with comorbidities. Phase III studies that compare these
      third-generation drugs are warranted to draw definitive conclusion about the best
      approach in these patients.

PMID- 18824451
TI  - Unusual tumor response and toxicity from radiation and concurrent erlotinib for
      non-small-cell lung cancer.
AB  - We report a case of a never-smoker female with non-small-cell lung cancer (NSCLC)
      who experienced a striking tumor response to combined low-dose radiation and the
      epidermal growth factor receptor inhibitor erlotinib, even though erlotinib alone
      was not effective in preventing tumor progression. Furthermore, the patient
      developed symptomatic pneumonitis, which is unusual for the small volume of lung
      that was exposed to a significant dose of radiation. This case demonstrates that
      combination therapy with radiation and erlotinib has the potential to
      significantly benefit a subset of patients with NSCLC in addition to those
      approximately 10% who have tumors which respond to erlotinib alone. It also
      highlights the potential risks of molecular targeted radiation therapy.

PMID- 18824454
TI  - Retraction notice. Management of central airway obstruction.

PMID- 18824456
TI  - Rapid method for testing the susceptibility of Aspergillus fumigatus to
      amphotericin B, itraconazole, voriconazole and posaconazole by assessment of
      oxygen consumption.
AB  - OBJECTIVES: Antifungal stress conditions affect fungal germination and growth.
      The assessment of oxygen consumption resulting from the challenge of Aspergillus
      fumigatus conidia with antifungal agents might be predictive of the
      susceptibility of this species to the agents evaluated. METHODS: The antifungal
      susceptibilities of A. fumigatus to amphotericin B, itraconazole, voriconazole
      and posaconazole were evaluated for 20 clinical strains by two methods: the rapid
      assessment of oxygen consumption and the CLSI M38-A2 microdilution method. For
      the determination of oxygen consumption, conidia were suspended in RPMI 1640
      medium with two different concentrations of each antifungal drug (0.25 and 2
      mg/L); the oxygen consumption was quantified in a biological oxygen monitor.
      RESULTS: A. fumigatus strains showed a wide spectrum of amphotericin B,
      itraconazole and voriconazole MICs (0.06 to >16 mg/L), but posaconazole MICs
      ranged from 0.06 to 1 mg/L. Distinct respiratory kinetics, which corresponded to
      the MIC results, were found. Strains with the highest itraconazole and
      voriconazole MICs grew faster, undoubtedly consuming the oxygen available in the
      liquid medium. The reproducibility of this new method was adequate (87%), as well
      as the agreement with the CLSI method (85%). CONCLUSIONS: Although the potential
      of this new and rapid method (4-8 versus 48 h CLSI method) for evaluating the
      susceptibility of A. fumigatus to the antifungal agents has been demonstrated by
      these preliminary results, further collaborative studies with more isolates
      should better assess the value of this methodology for testing isolates in the
      clinical laboratory.

PMID- 18824457
TI  - An HPLC assay for daptomycin in serum.

PMID- 18824458
TI  - Posaconazole concentrations in the central nervous system.

PMID- 18824459
TI  - Comparison of killing activity of caspofungin against Candida parapsilosis,
      Candida orthopsilosis and Candida metapsilosis.

PMID- 18824460
TI  - Population pharmacokinetics of ritonavir-boosted saquinavir regimens in HIV
      infected individuals.
AB  - OBJECTIVES: The aim of this study was to develop and validate a population
      pharmacokinetic model in order to describe ritonavir-boosted saquinavir
      concentrations dosed twice and once daily in human immunodeficiency virus (HIV)
      infected patients from the UK, Uganda and Thailand and to identify factors that
      may influence saquinavir pharmacokinetics. METHODS: Pharmacokinetic data from 10
      clinical studies were combined. Non-linear mixed effects modelling (NONMEM
      version V) was applied to determine the saquinavir pharmacokinetic parameters,
      interindividual/interoccasion variability (IIV/IOV) and residual error. Various
      covariates potentially related to saquinavir pharmacokinetics were explored, and
      the final model was validated by means of 95% prediction interval and testing the
      predictive performance of the model with data not included in the model-building
      process. RESULTS: Ninety-seven patients were included from the UK (n = 52),
      Uganda (n = 18) and Thailand (n = 27), contributing 347 saquinavir profiles (1-14
      profiles per patient). A one-compartment model with zero-order absorption and lag
      time best described the data with IIV/IOV on apparent oral clearance (CL/F) and
      volume of distribution (V/F) and with IIV on duration and absorption lag-time.
      The ritonavir area under the curve over the dosing interval was significantly
      associated with saquinavir CL/F and V/F. A typical patient from the UK had
      approximately 1.5- and 3-fold higher saquinavir CL/F compared with patients from
      Uganda (89.0 versus 49.8 L/h) and Thailand (89.0 versus 26.7 L/h), respectively.
      CONCLUSIONS: A model to characterize ritonavir-boosted saquinavir
      pharmacokinetics in HIV-infected adults has been developed and validated. The
      model could be used for dosage adaptation following therapeutic drug monitoring
      and to assess patients' suitability for once-daily boosted saquinavir therapy.

PMID- 18824461
TI  - Diverging associations of an intended early invasive strategy compared with
      actual revascularization, and outcome in patients with non-ST-segment elevation
      acute coronary syndrome: the problem of treatment selection bias.
AB  - AIMS: In several observational studies, revascularization is associated with
      substantial reduction in mortality in patients with non-ST-segment elevation
      acute coronary syndrome (nSTE-ACS). This has strengthened the belief that routine
      early angiography would lead to a reduction in mortality. We investigated the
      association between actual in-hospital revascularization and long-term outcome in
      patients with nSTE-ACS included in the ICTUS trial. METHODS AND RESULTS: The
      study population of the present analysis consists of ICTUS participants who were
      discharged alive after initial hospitalization. The ICTUS trial was a randomized,
      controlled trial in which 1200 patients were randomized to an early invasive or
      selective invasive strategy. The endpoints were death from hospital discharge
      until 4 year follow-up and death or spontaneous myocardial infarction (MI) until
      3 years. Among 1189 patients discharged alive, 691 (58%) underwent
      revascularization during initial hospitalization. In multivariable Cox regression
      analyses, in-hospital revascularization was independently associated with a
      reduction in 4 year mortality and 3 year event rate of death or spontaneous MI:
      hazard ratio (HR) 0.59 [95% confidence interval (CI) 0.37-0.96] and 0.46 (95% CI
      0.31-0.68). However, when intention-to-treat analysis was performed, no
      differences in cumulative event rates were observed between the early invasive
      and selective invasive strategies: HR 1.10 (95% CI 0.70-1.74) for death and 1.27
      (95% CI 0.88-1.85) for death or spontaneous MI. CONCLUSION: The ICTUS trial did
      not show that an early invasive strategy resulted in a better outcome than a
      selective invasive strategy in patients with nSTE-ACS. However, similar to
      retrospective analyses from observational studies, actual revascularization was
      associated with lower mortality and fewer MI. Whether an early invasive strategy
      leads to a better outcome than a selective invasive strategy cannot be inferred
      from the observation that revascularized patients have a better prognosis in non
      randomized studies.

PMID- 18824462
TI  - Endothelial progenitor cell levels in obese men with the metabolic syndrome and
      the effect of simvastatin monotherapy vs. simvastatin/ezetimibe combination
      therapy.
AB  - AIMS: Endothelial progenitor cells (EPCs) contribute to endothelial regeneration
      and thereby protect against cardiovascular disease (CVD). Patients with manifest
      CVD have reduced EPC levels, but it is not clear if this also occurs in subjects
      at high CVD risk without manifest atherosclerotic disease. Therefore, we aimed to
      first, measure circulating levels of EPCs in subjects without manifest CVD but at
      high cardiovascular risk due to obesity and presence of the metabolic syndrome.
      Second, we evaluated the effect on EPC levels of two lipid-lowering treatments.
      METHODS AND RESULTS: Circulating CD34+KDR+ EPC levels were reduced by nearly 40%
      in obese men with the metabolic syndrome compared to non-obese healthy controls
      (331 +/- 193 vs. 543 +/- 164 EPC/mL, P = 0.006). In a randomized double-blind
      cross-over study comparing intensive lipid-lowering treatment using 80 mg
      simvastatin mono-treatment with combination treatment of 10 mg simvastatin and 10
      mg ezetimibe, we found a similar treatment effect on EPC levels. Secondary
      analyses of these data suggested that both treatment regimens had increased
      circulating EPCs to control levels (626 +/- 428 after combination treatment, P <
      0.01; 524 +/- 372 EPC/mL after monotherapy, P < 0.05). Serum levels of EPC
      mobilizing factor SCF-sR correlated with reduced EPC levels and normalized
      concurrently with treatment. CONCLUSION: EPC levels are reduced in apparently
      healthy men with abdominal obesity and the metabolic syndrome, even in the
      absence of manifest CVD. This is important as EPCs contribute to endothelial
      regeneration and thereby protect against CVD. SCF-sR may be a candidate serum
      marker of circulating EPC levels. Treatment with low-dose statin with ezetimibe
      combination therapy or high-dose statin monotherapy has similar effects on the
      reduced EPC levels.

PMID- 18824463
TI  - NICE public health guidance: what's new?

PMID- 18824464
TI  - Docking of cytochrome c6 and plastocyanin to the aa3-type cytochrome c oxidase in
      the cyanobacterium Phormidium laminosum.
AB  - The interactions between redox proteins are transient in nature. Therefore, very
      few crystal structures are available for the complexes formed between these
      proteins. Computational docking simulations thus provide a useful alternative
      method for studying the interactions between electron transfer proteins. In this
      paper, we have studied the interactions between the aa(3)-type cytochrome c
      oxidase of the cyanobacterium Phormidium laminosum and its redox partners
      plastocyanin and cytochrome c(6) using a combination of comparative modelling
      techniques and docking simulations. Rigid-body docking orientations were scored
      with a combined energy function that accounts for electrostatics and desolvation.
      These simulations have identified two plausible docking sites, one of which
      appears to be unique to the binding of plastocyanin to the oxidase. This unique
      binding site may be due to the presence of a long loop region in the subunit II
      of cyanobacterial oxidases. Control simulations were performed with the ba(3)
      type cytochrome c oxidase and its redox partner cytochrome c(552) from Thermus
      thermophilus. The docking between cytochrome c oxidase and its redox partners
      plastocyanin and cytochrome c(6) is dominated by hydrophobic residues, a feature
      already observed from kinetic and structural studies in other complexes of P.
      laminosum (e.g. plastocyanin or cytochrome c(6) with cytochrome f and photosystem
      I).

PMID- 18824465
TI  - Facile, reagentless and in situ release of Escherichia coli intracellular enzymes
      by heat-inducible autolytic vector for high-throughput screening.
AB  - In an effect to broaden the application of the heat-inducible autolytic vector
      pUC18-cI857/p(R)-SRRz-rrnB previously developed, a new vector pUC18
      cI857/p(R)(T41C)-SRRz-rrnB (pEAS-1b) was quantitatively characterized under
      various growth temperatures, heat induction temperatures and durations, and IPTG
      (isopropyl beta-d-thiogalactoside) induction times, after resolving its erratic
      lysis profile found previously. Escherichia coli BL21 cells harboring this vector
      grew well at temperatures <36 degrees C, and lysed efficiently (97.0 +/- 0.8%)
      just 0.5 h after heat induction at 42 degrees C for 30 min when cell growth was
      performed at 35 degrees C. Application of this autolytic vector either in 96-well
      plates, or on nitrocellulose membranes, or on agar plates led to facile,
      efficient and consistent release of intracellular recombinant enzymes (e.g., a
      lysis efficiency of 91.8 +/- 1.1% was obtained in 96-well plates). Further
      application in directed evolution was illustrated by improving the
      thermostability of amadoriase using this vector. This reagentless and in situ
      cell lysis method has the potentials for lysis of miniaturized samples in
      clinical diagnosis and bioanalytical detection, and even for lysis of cells in
      the microarray format.

PMID- 18824466
TI  - Apparently conclusive meta-analyses may be inconclusive--Trial sequential
      analysis adjustment of random error risk due to repetitive testing of
      accumulating data in apparently conclusive neonatal meta-analyses.
AB  - BACKGROUND: Random error may cause misleading evidence in meta-analyses. The
      required number of participants in a meta-analysis (i.e. information size) should
      be at least as large as an adequately powered single trial. Trial sequential
      analysis (TSA) may reduce risk of random errors due to repetitive testing of
      accumulating data by evaluating meta-analyses not reaching the information size
      with monitoring boundaries. This is analogous to sequential monitoring boundaries
      in a single trial. METHODS: We selected apparently conclusive (P </= 0.05)
      Cochrane neonatal meta-analyses. We applied heterogeneity-adjusted and unadjusted
      TSA on these meta-analyses by calculating the information size, the monitoring
      boundaries, and the cumulative Z-statistic after each trial. We identified the
      proportion of meta-analyses that did not reach the required information size and
      the proportion of these meta-analyses in which the Z-curve did not cross the
      monitoring boundaries. RESULTS: Of 54 apparently conclusive meta-analyses, 39
      (72%) did not reach the heterogeneity-adjusted information size required to
      accept or reject an intervention effect of 25% relative risk reduction. Of these
      39, 19 meta-analyses (49%) were considered inconclusive, because the cumulative Z
      curve did not cross the monitoring boundaries. The median number of participants
      required to reach the required information size was 1591 (range, 339-6149). TSA
      without heterogeneity adjustment largely confirmed these results. CONCLUSIONS:
      Many apparently conclusive Cochrane neonatal meta-analyses may become
      inconclusive when the statistical analyses take into account the risk of random
      error due to repetitive testing.

PMID- 18824467
TI  - Can trial sequential monitoring boundaries reduce spurious inferences from meta
      analyses?
AB  - BACKGROUND: Results from apparently conclusive meta-analyses may be false. A
      limited number of events from a few small trials and the associated random error
      may be under-recognized sources of spurious findings. The information size (IS,
      i.e. number of participants) required for a reliable and conclusive meta-analysis
      should be no less rigorous than the sample size of a single, optimally powered
      randomized clinical trial. If a meta-analysis is conducted before a sufficient IS
      is reached, it should be evaluated in a manner that accounts for the increased
      risk that the result might represent a chance finding (i.e. applying trial
      sequential monitoring boundaries). METHODS: We analysed 33 meta-analyses with a
      sufficient IS to detect a treatment effect of 15% relative risk reduction (RRR).
      We successively monitored the results of the meta-analyses by generating interim
      cumulative meta-analyses after each included trial and evaluated their results
      using a conventional statistical criterion (alpha = 0.05) and two-sided Lan
      DeMets monitoring boundaries. We examined the proportion of false positive
      results and important inaccuracies in estimates of treatment effects that
      resulted from the two approaches. RESULTS: Using the random-effects model and
      final data, 12 of the meta-analyses yielded P > alpha = 0.05, and 21 yielded P
      </= alpha = 0.05. False positive interim results were observed in 3 out of 12
      meta-analyses with P > alpha = 0.05. The monitoring boundaries eliminated all
      false positives. Important inaccuracies in estimates were observed in 6 out of 21
      meta-analyses using the conventional P </= alpha = 0.05 and 0 out of 21 using the
      monitoring boundaries. CONCLUSIONS: Evaluating statistical inference with trial
      sequential monitoring boundaries when meta-analyses fall short of a required IS
      may reduce the risk of false positive results and important inaccurate effect
      estimates.

PMID- 18824468
TI  - Commentary: Alcohol poisoning in Russia: implications for monitoring and
      comparative risk factor assessment.

PMID- 18824469
TI  - Ovarian function: a theory of relativity.
AB  - Kol and Homburg recently hypothesized in these pages that the change, rather than
      currently evaluated absolute hormone values, is important for biological
      processes. We fully agree, but wish, with this communication, to add to their
      concept: opposing forces, balancing each other, in order to maintain a system's
      stability, permeates nature. Loss of such equilibrium, in turn, results in
      systemic malfunctions with, at times, adverse consequences. Extrapolating to Kol
      and Homburg's hypothesis, this observation would suggest that not only changes in
      any given hormone carry biological messages, but that final message derives from
      hormonal ratios between hormones which oppose each other in physiological
      effects. In full concurrence to Kol and Homburg, this concept could give rise to
      better diagnosis and treatment of infertility problems.

PMID- 18824470
TI  - Ovarian epithelial dysplasia after ovulation induction: time and dose effects.
AB  - BACKGROUND: Ovarian epithelial dysplasia was first described after prophylactic
      oophorectomies for genetic risk. Ovarian stimulation has been considered as a
      risk factor of ovarian cancer by Fathalla's incessant ovulation theory. In this
      study, we have investigated the risk of ovarian dysplasia after ovulation
      induction. METHODS: We reviewed 99 oophorectomies or cystectomies between 1990
      and 2005 divided them into two groups: previous in vitro fertilization (n = 37)
      and a panel of fertile controls (n = 62). Eleven epithelial cytological and
      architectural features were defined and an ovarian epithelial dysplasia score was
      calculated to quantify the degree of ovarian epithelial abnormalities. RESULTS:
      All the ovaries were macroscopically non-cancerous except in two patients (one
      endometrioid cancer and one borderline tumour). The mean ovarian dysplasia score
      was significantly higher in the ovulation induction group than in the control
      group (7.64 versus 3.62, P = 0.0002). We also found a relationship between the
      number of ovulation-inducted cycles and the severity of ovarian dysplasia ('dose
      effect') and a relationship between time after the end of ovulation induction
      (over 7 years) and the severity of ovarian dysplasia ('time-effect').
      CONCLUSIONS: There is probably a relationship between ovarian epithelial
      dysplasia and either ovulation inducing drugs or infertility. By Fathalla's
      incessant ovulation theory, 'the dose effect and the time effect' of ovarian
      stimulation may explain ovarian dysplasia formation.

PMID- 18824471
TI  - Markers that define stemness in ESC are unable to identify the totipotent cells
      in human preimplantation embryos.
AB  - BACKGROUND: During human preimplantation development, early blastomeres are
      believed to be totipotent. It is likely, however, that blastomeres are allocated
      to a specific lineage prior to any morphological differentiation. NANOG, SOX2 and
      SALL4 are transcription factors that play a key role in controlling stemness in
      embryonic stem cells (ESC) and are therefore candidate markers for developmental
      triggers in early embryos. KRT18, a trophoblast-determining gene, may mark early
      differentiation. Examining the expression pattern of these genes may inform us
      about when and in which cells totipotency is lost during early human development.
      METHODS: Thirtheen oocytes, 124 preimplantation embryos and 7 human embryonic
      stem cell (hESC) lines were examined for the presence of NANOG, SOX2, SALL4 or
      KRT18 proteins using immunostaining and confocal microscopy. RESULTS: All
      stemness markers were expressed in the hESC, but none of them was specific for
      totipotent cells during human preimplantation development, and none of them
      seemed to mark cells allocated to the inner cell mass (ICM) or trophectoderm.
      After lineage specification, only the nuclear expression of NANOG and SOX2 became
      restricted to the ICM, at least to some cells because only a subpopulation
      expressed NANOG. KRT18 expression was seen for the first time during compaction
      in some outer cells. KRT18 was not expressed in hESC. CONCLUSION: We conclude
      that the protein expression patterns of markers that define stemness in ESC do
      not identify the totipotent cells in human preimplantation embryos. Assessing the
      presence of KRT18 proteins implied that the outer cells of compacting embryos
      have probably lost their totipotent competence prior to any visible
      differentiation.

PMID- 18824472
TI  - A potential tolerogenic immune mechanism in a trophoblast cell line through the
      activation of chemokine-induced T cell death and regulatory T cell modulation.
AB  - BACKGROUND: Successful implantation is followed by a local pro-inflammatory and
      Th1 response, subsequently controlled by Th2. Regulated upon activation, normal T
      cell expressed and secreted (RANTES) promotes a Th1 response and is implicated as
      a physiologic tolerogenic factor; therefore, we studied its potential role in the
      trophoblast-maternal leukocyte dialog. METHODS: We performed co-cultures of
      immortalized trophoblast cell line (Swan 71) and peripheral blood mononuclear
      cells (PBMCs) from fertile women (n = 23) or with recurrent spontaneous abortions
      (n = 18, RSA). After 24 and 48 h, supernatant and cells were analyzed by enzyme
      linked immunosorbent assay, fluorescence-activated cell sorting, Western blot and
      apoptosis assay. To investigate the physiological effects at peripheral level, we
      co-cultured maternal and paternal PBMCs with conditioned media from Swan cells
      and progesterone. RESULTS: Following interaction of maternal PBMCs and
      trophoblast cells, RANTES production increased (P < 0.05) and was accompanied by
      low levels of interferon gamma, interleukin-12 p70 and high levels of tumor
      necrosis factor-alpha, nitrites and leukemia-inhibitory factor. RANTES production
      resulted in elevated apoptosis of potentially deleterious maternal CD3+
      lymphocytes, accompanied by a decrease in the proliferative maternal response.
      During fetal-maternal dialog, the anti-RANTES antibody significantly reduced the
      frequency of CD4+CD25+Foxp3+ cells (P < 0.05) and was associated with trophoblast
      cell survival. However, co-cultures of Swan cells and RSA-PBMCs displayed a
      differential RANTES kinetics, lower levels of regulatory T cells (Tregs) and
      CD3+annexin-V+cells, accompanied by higher levels of apoptotic trophoblast cells.
      CONCLUSIONS: RANTES promotes an adequate pro-implantatory microenvironment that
      influences trophoblast cell survival and modulates the balance of maternal Treg/T
      effector lymphocytes in favor of maternal tolerance.

PMID- 18824473
TI  - Response of cytoplasmic pH to anoxia in plant tissues with altered activities of
      fermentation enzymes: application of methyl phosphonate as an NMR pH probe.
AB  - BACKGROUND AND AIMS: Acidification of the cytoplasm is a commonly observed
      response to oxygen deprivation in plant tissues that are intolerant of anoxia.
      The response was monitored in plant tissues with altered levels of lactate
      dehydrogenase (LDH) and pyruvate decarboxylase (PDC) with the aim of assessing
      the contribution of the targeted enzymes to cytoplasmic pH (pH(cyt)) regulation.
      METHODS: The pH(cyt) was measured by in vivo (31)P nuclear magnetic resonance
      (NMR) spectroscopy using methyl phosphonate (MeP) as a pH probe. The potential
      toxicity of MeP was investigated by analysing its effect on the metabolism of
      radiolabelled glucose. KEY RESULTS: MeP accumulated to detectable levels in the
      cytoplasm and vacuole of plant tissues exposed to millimolar concentrations of
      MeP, and the pH-dependent (31)P NMR signals provided a convenient method for
      measuring pH(cyt) values in tissues with poorly defined signals from the
      cytoplasmic inorganic phosphate pool. Pretreatment of potato (Solanum tuberosum)
      tuber slices with 5 mm MeP for 24 h did not affect the metabolism of [U
      (14)C]glucose or the pattern of (14)CO(2) release from specifically labelled
      [(14)C]-substrates. Time-courses of pH(cyt) measured before, during and after an
      anoxic episode in potato tuber tissues with reduced activities of LDH, or in
      tobacco (Nicotiana tabacum) leaves with increased activities of PDC, were
      indistinguishable from their respective controls. CONCLUSIONS: MeP can be used as
      a low toxicity (31)P NMR probe for measuring intracellular pH values in plant
      tissues with altered levels of fermentation enzymes. The measurements on
      transgenic tobacco leaves suggest that the changes in pH(cyt) during an anoxic
      episode are not dominated by fermentation processes; while the pH changes in the
      potato tuber tissue with reduced LDH activity show that the affected isozymes do
      not influence the anoxic pH response.

PMID- 18824474
TI  - Evolutionary analysis of the Sub1 gene cluster that confers submergence tolerance
      to domesticated rice.
AB  - BACKGROUND AND AIMS: Tolerance of complete submergence is recognized in a small
      number of accessions of domesticated Asian rice (Oryza sativa) and can be
      conferred by the Sub1A-1 gene of the polygenic Submergence-1 (Sub1) locus. In all
      O. sativa varieties, the Sub1 locus encodes the ethylene-responsive factor (ERF)
      genes Sub1B and Sub1C. A third paralogous ERF gene, Sub1A, is limited to a subset
      of indica accessions. It is thought that O. sativa was domesticated from the gene
      pools of the wild perennial species O. rufipogon Griff. and/or the annual species
      O. nivara Sharma et Shastry. The aim of this study was to evaluate the
      orthologues of the Sub1 locus in the closest relatives of O. sativa to provide
      insight into the origin of the gene and allelic variation of the Sub1 locus.
      METHODS: Orthologues of the Sub1 genes were isolated from O. rufipogon and O.
      nivara by use of oligonucleotide primers corresponding to the most highly
      conserved regions of the Sub1 genes of domesticated rice. The phylogenetic
      relatedness of Sub1 genes of O. sativa and its wild relatives was evaluated. KEY
      RESULTS AND CONCLUSIONS: Both O. rufipogon and O. nivara possess two Sub1 gene
      orthologues with strong sequence identity to the Sub1B and Sub1C alleles of
      cultivated rice. The phylogeny of the Sub1 genes of the domesticated and wild
      rice suggests that Sub1A arose from duplication of Sub1B. Variation in Sub1B
      alleles is correlated with the absence or presence of Sub1A. Together, the
      results indicate that genetic variation at the Sub1 locus is due to gene
      duplication and divergence that have occurred both prior to and after rice
      domestication.

PMID- 18824475
TI  - Strong cation exchange-based fractionation of Lys-N-generated peptides
      facilitates the targeted analysis of post-translational modifications.
AB  - In proteomics multi-dimensional fractionation techniques are widely used to
      reduce the complexity of peptide mixtures subjected to mass spectrometric
      analysis. Here, we describe the sequential use of strong cation exchange and
      reversed phase liquid chromatography in the separation of peptides generated by a
      relatively little explored metallo-endopeptidase with Lys-N cleavage specificity.
      When such proteolytic peptides are subjected to low-pH strong cation exchange we
      obtain fractionation profiles in which peptides from different functional
      categories are well separated. The four categories we distinguish and are able to
      separate to near completion are (I) acetylated N-terminal peptides; (II) singly
      phosphorylated peptides containing a single basic (Lys) residue; (III) peptides
      containing a single basic (Lys) residue; and (IV) peptides containing more than
      one basic residue. Analyzing these peptides by LC-MS/MS using an ion trap with
      both collision as well as electron transfer-induced dissociation provides unique
      optimal targeted strategies for proteome analysis. The acetylated peptides in
      category I can be identified confidently by both CID and ETcaD, whereby the ETcaD
      spectra are dominated by sequence informative Z-ion series. For the
      phosphorylated peptides in category II and the "normal" single Lys containing
      peptides in category III ETcaD provides unique straightforward sequence ladders
      of c'-ions, from which the exact location of possible phosphorylation sites can
      be easily determined. The later fractions, category IV, require analysis by both
      ETcaD and CID, where it is shown that electron transfer dissociation performs
      relatively well for these multiple basic residues containing peptides, as is
      expected. We argue that the well resolved separation of functional categories of
      peptides observed is characteristic for Lys-N-generated peptides. Overall, the
      combination of Lys-N proteolysis, low-pH strong cation exchange, and reversed
      phase separation, with CID and ETD induced fragmentation, adds a new very
      powerful method to the toolbox of proteomic analyses.

PMID- 18824476
TI  - Glycosylation specific for adhesion molecules in epidermis and its receptor
      revealed by glycoform-focused reverse genomics.
AB  - Glycosylation of proteins greatly affects their structure and function, but
      traditional genomics and transcriptomics are not able to precisely capture tissue
      or species-specific glycosylation patterns. We describe here a novel approach to
      link different "omics" data based on exhaustive quantitative glycomics of murine
      dermis and epidermis. We first examined the dermal and epidermal N-glycome of
      mouse by a recently established glycoblotting technique. We found that the
      Galalpha1-3Gal epitope was solely expressed in epidermis tissue and was
      preferentially attached to adhesion molecules in a glycosylation site-specific
      manner. Clarified glycomic and protemic information combined with publicly
      available microarray data sets allowed us to identify galectin-3 as a receptor of
      Galalpha1-3Gal epitope. These findings provide mechanistic insight into the
      causal connection between the genotype and the phenotype seen in alpha3GalT-1
      deficient mice and transgenic mice expressing endo-beta-galactosidase C. Because
      humans do not possess the Galalpha1-3Gal structure on their tissues, we further
      examined the human dermal and epidermal N-glycome. Comparative glycomics revealed
      that the GalNAcbeta1-4GlcNAc (N,N'-diacetyllactosediamine) epitope, instead of
      the Galalpha1-3Gal epitope, was highly expressed in human epidermis.

PMID- 18824477
TI  - Yeast ribosomal protein L10 helps coordinate tRNA movement through the large
      subunit.
AB  - Yeast ribosomal protein L10 (E. coli L16) is located at the center of a
      topological nexus that connects many functional regions of the large subunit.
      This essential protein has previously been implicated in processes as diverse as
      ribosome biogenesis, translational fidelity and mRNA stability. Here, the
      inability to maintain the yeast Killer virus was used as a proxy for large
      subunit defects to identify a series of L10 mutants. These mapped to roughly four
      discrete regions of the protein. A detailed analysis of mutants located in the N
      terminal 'hook' of L10, which inserts into the bulge of 25S rRNA helix 89,
      revealed strong effects on rRNA structure corresponding to the entire path taken
      by the tRNA 3' end as it moves through the large subunit during the elongation
      cycle. The mutant-induced structural changes are wide-ranging, affecting ribosome
      biogenesis, elongation factor binding, drug resistance/hypersensitivity,
      translational fidelity and virus maintenance. The importance of L10 as a
      potential transducer of information through the ribosome, and of a possible role
      of its N-terminal domain in switching between the pre- and post-translocational
      states are discussed.

PMID- 18824478
TI  - Hairpin structures formed by alpha satellite DNA of human centromeres are cleaved
      by human topoisomerase IIalpha.
AB  - Although centromere function has been conserved through evolution, apparently no
      interspecies consensus DNA sequence exists. Instead, centromere DNA may be
      interconnected through the formation of certain DNA structures creating
      topological binding sites for centromeric proteins. DNA topoisomerase II is a
      protein, which is located at centromeres, and enzymatic topoisomerase II activity
      correlates with centromere activity in human cells. It is therefore possible that
      topoisomerase II recognizes and interacts with the alpha satellite DNA of human
      centromeres through an interaction with potential DNA structures formed solely at
      active centromeres. In the present study, human topoisomerase IIalpha-mediated
      cleavage at centromeric DNA sequences was examined in vitro. The investigation
      has revealed that the enzyme recognizes and cleaves a specific hairpin structure
      formed by alpha satellite DNA. The topoisomerase introduces a single-stranded
      break at the hairpin loop in a reaction, where DNA ligation is partly uncoupled
      from the cleavage reaction. A mutational analysis has revealed, which features of
      the hairpin are required for topoisomerease IIalpha-mediated cleavage. Based on
      this a model is discussed, where topoisomerase II interacts with two hairpins as
      a mediator of centromere cohesion.

PMID- 18824479
TI  - GiardiaDB and TrichDB: integrated genomic resources for the eukaryotic protist
      pathogens Giardia lamblia and Trichomonas vaginalis.
AB  - GiardiaDB (http://GiardiaDB.org) and TrichDB (http://TrichDB.org) house the
      genome databases for Giardia lamblia and Trichomonas vaginalis, respectively, and
      represent the latest additions to the EuPathDB (http://EuPathDB.org) family of
      functional genomic databases. GiardiaDB and TrichDB employ the same framework as
      other EuPathDB sites (CryptoDB, PlasmoDB and ToxoDB), supporting fully integrated
      and searchable databases. Genomic-scale data available via these resources may be
      queried based on BLAST searches, annotation keywords and gene ID searches, GO
      terms, sequence motifs and other protein characteristics. Functional queries may
      also be formulated, based on transcript and protein expression data from a
      variety of platforms. Phylogenetic relationships may also be interrogated. The
      ability to combine the results from independent queries, and to store queries and
      query results for future use facilitates complex, genome-wide mining of
      functional genomic data.

PMID- 18824480
TI  - Amino acid sequence variations in Nicotiana CRR4 orthologs determine the species
      specific efficiency of RNA editing in plastids.
AB  - In flowering plants, RNA editing is a posttranscriptional process that converts
      specific C to U in organelle mRNAs. Nicotiana tabacum is an allotetraploid
      species derived from the progenitors of Nicotiana sylvestris and Nicotiana
      tomentosiformis. These Nicotiana species have been used as a model for
      understanding the mechanism and evolution of RNA editing in plastids. In
      Nicotiana species, the ndhD-1 site is edited to create the translational
      initiation codon of ndhD that encodes a subunit of the NAD(P)H dehydrogenease
      (NDH) complex. An analysis of this RNA editing revealed that editing efficiency
      in N. tomentosiformis is lower (15%) than that in N. tabacum (42%) and N.
      sylvestris (37%). However, this level of editing is sufficient for accumulating
      the NDH complex and its activity. The heterogous complementation of Arabidopsis
      crr4-3 mutant, in which RNA editing of ndhD-1 is completely impaired, with CRR4
      orthologous genes derived from Nicotiana species suggested that the reduction in
      editing efficiency in N. tomentosiformis is caused by amino acid variations
      accumulating in CRR4.

PMID- 18824481
TI  - Nonradioactive, ultrasensitive site-specific protein-protein photocrosslinking:
      interactions of alpha-helix 2 of TATA-binding protein with general transcription
      factor TFIIA and transcriptional repressor NC2.
AB  - We have developed an approach that enables nonradioactive, ultrasensitive
      (attamole sensitivity) site-specific protein-protein photocrosslinking, and we
      have applied the approach to the analysis of interactions of alpha-helix 2 (H2)
      of human TATA-element binding protein (TBP) with general transcription factor
      TFIIA and transcriptional repressor NC2. We have found that TBP H2 can be
      crosslinked to TFIIA in the TFIIA-TBP-DNA complex and in higher order
      transcription-initiation complexes, and we have mapped the crosslink to the
      'connector' region of the TFIIA alpha/beta subunit (TFIIAalpha/beta). We further
      have found that TBP H2 can be crosslinked to NC2 in the NC2-TBP-DNA complex, and
      we have mapped the crosslink to the C-terminal 'tail' of the NC2 alpha-subunit
      (NC2alpha). Interactions of TBP H2 with the TFIIAalpha/beta connector and the
      NC2alpha C-terminal tail were not observed in crystal structures of TFIIA-TBP-DNA
      and NC2-TBP-DNA complexes, since relevant segments of TFIIA and NC2 were not
      present in truncated TFIIA and NC2 derivatives used for crystallization. We
      propose that interactions of TBP H2 with the TFIIAalpha/beta connector and the
      NC2alpha C-terminal tail provide an explanation for genetic results suggesting
      importance of TBP H2 in TBP-TFIIA interactions and TBP-NC2 interactions, and
      provide an explanation-steric exclusion-for competition between TFIIA and NC2.

PMID- 18824482
TI  - Commentary: Controversies in NICE guidance on chronic kidney disease.

PMID- 18824484
TI  - EU parliament backs 30 minutes' exercise a day for all children to tackle
      obesity.

PMID- 18824485
TI  - Economic evaluation of health interventions.

PMID- 18824486
TI  - Early identification and management of chronic kidney disease: summary of NICE
      guidance.

PMID- 18824487
TI  - Preparticipation screening for cardiovascular abnormalities in young competitive
      athletes.

PMID- 18824488
TI  - Developing and evaluating complex interventions: the new Medical Research Council
      guidance.

PMID- 18824490
TI  - Short intensive radiation courses may work as well as standard ones.

PMID- 18824491
TI  - Complications of open stent-graft in treatment of aortic dissection.
AB  - Open stent-graft has been used in the treatment of aortic dissection in recent
      years. Two device related complications happened in two patients. One was
      stenosis of the true lumen in the descending aorta caused by infolding of the
      distal end of the stent-graft immediately after its deployment. The other one was
      a new intima tear at the distal end of the stent-graft caused by full expansion
      of the stent-graft two years after stent-graft implantation. With the refinement
      of the device and enrichment of surgeons' experience, such complications could be
      avoided in the future.

PMID- 18824492
TI  - Bilocular pericardial cyst in an aberrant location.
AB  - Pericardial cysts classically are found in the right or left cardiophrenic angle
      and rarely are located outside of this location. An 82-year-old man presented
      with an asymptomatic cystic mass on chest CT-scan located in the upper right
      mediastinum and measuring 7 x 6 x 4 cm. A follow-up chest CT-scan 12 months later
      showed that the cyst had increased in size to where it now measured 10 x 9 x 8 cm
      and was noted to be dislocating and compressing the superior vena cava. The
      patient underwent surgical excision because of the uncertain diagnosis and the
      compression of contiguous organs. Two cystic masses were able to be completely
      excised intact. A definitive diagnosis of double pericardial cyst was
      histopathologically confirmed. Radiological findings of a pericardial cyst in the
      upper mediastinum are extremely rare. In particular there have been no reports of
      bilocular or double pericardial cysts.

PMID- 18824493
TI  - Genetic analysis of salt-sensitive hypertension in Dahl rats reveals a link
      between cardiac fibrosis and high cholesterol.
AB  - AIMS: Previously we confirmed an important role of rat chromosome 19 (RNO19) for
      salt-sensitive hypertension and target organ damage in male Dahl salt-sensitive
      rats (SS rats). The aim of this study was to further analyse the basis of left
      ventricular (LV) fibrosis development in both male and female rats in this model.
      To this end we utilized a consomic SS-19(SHR) rat strain in which RNO19 was
      transferred from spontaneously hypertensive rats (SHR) into the susceptible
      background of SS. METHODS AND RESULTS: We compared the effects of low- (0.2%
      NaCl) and high-salt (4% NaCl) diet on the development of hypertension, blood
      lipids and LV fibrosis in male and female SS, SHR, and SS-19(SHR) rats. Systolic
      blood pressure was significantly lower in male and female SS-19(SHR) compared
      with SS under both diets (P < 0.001). Relative LV weight was similarly reduced in
      SS-19(SHR) compared with SS in either sex. Plasma cholesterol concentrations were
      significantly elevated in high-salt fed male and female SS (141 +/- 6 and 110 +/-
      7 mg/dL) compared with SHR (47 +/- 2 and 62 +/- 8 mg/dL, P < 0.001) and were
      significantly lowered in male and female consomic rats (100 +/- 7 and 87 +/- 3
      mg/dL). Both LV interstitial fibrosis (LVIF) and perivascular fibrosis (LVPF)
      were significantly reduced in high-salt male and female SS-19(SHR). A significant
      correlation between cholesterol concentrations and LVPF (r = 0.464) and LVIF (r =
      0.401, P < 0.0001, respectively) was detected. Fibrosis parameters demonstrated
      no correlation with blood pressure, LV weight or plasma triglycerides
      concentrations. LV immunohistochemistry analysis showed a significant higher
      number of ED-1 positive cells in SS compared with SS-19(SHR). Depositions of
      collagen I and fibronectin were also greater in LV tissue of SS compared with SS
      19(SHR). CONCLUSION: Our findings point to a link between hypercholesterolemia
      and LV fibrosis in salt-sensitive hypertension of SS rats which is genetically
      modulated by RNO19.

PMID- 18824494
TI  - Ovulation suppression to protect against chemotherapy-induced ovarian toxicity:
      helpful or just hopeful?

PMID- 18824495
TI  - GnRH-analogues and oral contraceptives for fertility preservation in women during
      chemotherapy.
AB  - BACKGROUND: For preserving fertility in women during chemotherapy, the character
      of invasive techniques, such as ovarian cryopreservation and other techniques,
      await further experience. Meanwhile, non-invasive techniques have attempted to
      minimize the gonadotoxic effect of chemotherapy, by using gonadotrophin-releasing
      hormone-analogues (GnRH-a) or oral contraceptives (OC). METHODS: We performed a
      computerized MEDLINE search to identify articles published on fertility
      preservation using GnRH-a or OCs. RESULTS: Nine human-controlled studies reported
      the use of GnRH-a and four reported the use of OCs in parallel to chemotherapy.
      All nine studies analysing the effect of GnRH-a found lower rates of premature
      ovarian failure (POF) in patients receiving GnRH-a compared with the controls.
      Summarizing the studies resulted in 11.1% incidence of POF in patients who
      received GnRH-a compared with 55.5% incidence in the controls. Evidence using the
      fertility preserving effect of OC is limited. Two studies showed lower POF rates
      in OC-treated patients. The summarized data revealed a POF rate of 13.2% in
      patients who received OCs compared with that of 29.8% in the controls.
      CONCLUSIONS: The published clinical studies provide evidence, but do not prove
      statistically, that GnRH-a co-treatment reduces gonadotoxicity. Owing to the
      retrospective and non-randomized nature of most of the studies, definite
      conclusions concerning the reduction of POF by GnRH-a can still not be
      unequivocally drawn. As GnRH-a and OC have no serious side effects and as GnRH-a
      can even reduce chemotherapy-induced complications, such as severe
      menometrorrhagia, GnRH-a are considered by many clinicians as a clinically useful
      co-treatment in chemotherapy. The published clinical studies on OC also suggest a
      possible effect on the reduction of POF under certain conditions.

PMID- 18824496
TI  - Mitochondrial abnormalities in spinal and bulbar muscular atrophy.
AB  - Spinal and bulbar muscular atrophy (SBMA) is a motor neuron disease caused by
      polyglutamine expansion mutation in the androgen receptor (AR). We investigated
      whether the mutant protein alters mitochondrial function. We found that
      constitutive and doxycycline-induced expression of the mutant AR in MN-1 and PC12
      cells, respectively, are associated with depolarization of the mitochondrial
      membrane. This was mitigated by cyclosporine A, which inhibits opening of the
      mitochondrial permeability transition pore. We also found that the expression of
      the mutant protein in the presence of ligand results in an elevated level of
      reactive oxygen species, which is blocked by the treatment with the antioxidants
      co-enzyme Q10 and idebenone. The mutant protein in MN-1 cells also resulted in
      increased Bax, caspase 9 and caspase 3. We assessed the effects of mutant AR on
      the transcription of mitochondrial proteins and found altered expression of the
      peroxisome proliferator-activated receptor gamma coactivator 1 and the
      mitochondrial specific antioxidant superoxide dismutase-2 in affected tissues of
      SBMA knock-in mice. In addition, we found that the AR associates with
      mitochondria in cultured cells. This study thus provides evidence for
      mitochondrial dysfunction in SBMA cell and animal models, either through indirect
      effects on the transcription of nuclear-encoded mitochondrial genes or through
      direct effects of the mutant protein on mitochondria or both. These findings
      indicate possible benefit from mitochondrial therapy for SBMA.

PMID- 18824497
TI  - Pitfalls in the diagnosis and management of obstructive uterovaginal duplication:
      a series of 32 cases.
AB  - OBJECTIVES: Obstructive uterovaginal duplication is rare and frequently
      misdiagnosed. The aims of this study were to review all the patients managed for
      this malformation in our institution, evaluate their long-term outcomes, and
      discuss the embryologic origin of this malformation. METHODS: From 1984 to 2007,
      we treated 32 patients for obstructive uterovaginal duplication in our
      institution. We separated them in 2 groups (prepubertal [n = 8] and pubertal [n =
      24]) and analyzed their clinical and radiologic presentations and their
      treatments. Patients >18 years of age (n = 22) were recontacted. RESULTS: For the
      prepubertal group, the median age at diagnosis was 6 months. Postnatal ultrasound
      showed an absent ipsilateral kidney in 6 case subjects, although 4 patients had a
      prenatal diagnosis of ipsilateral multicystic dysplastic kidney. This renal
      anomaly was associated with a pelvic sonolucent mass in 3 case subjects, allowing
      us to prenatally suspect the diagnosis. All of the patients were cured by vaginal
      approach. For the pubertal group, the median delay of diagnosis after menarche
      was 9 months. Among patients managed in an emergency setting (n = 11), there were
      9 misdiagnoses with inappropriate abdominal surgeries, including 3 hysterectomies
      of the obstructed hemiuterus. Concerning long-term results, 5 patients were
      attempting to have children, with successful pregnancies for 4 of them. One
      patient suffered from infertility attributable to contralateral isthmic stenosis
      after a hysterectomy of the obstructed hemiuterus. CONCLUSIONS: Obstructive
      uterovaginal duplication is a benign pathology when properly managed. Therefore,
      management of abdominal pain in peripubertal girls should include systematic
      abdominal and gynecologic examinations completed by radiologic pelvic and renal
      evaluation. Surgical treatment should be performed by vaginal approach to avoid
      infertility. Concerning the origin of the malformation, the high association of
      prenatal dysplastic kidneys and postnatal absent kidneys suggests anomalies of
      both wolffian and mullerian duct development, contrasting with the classic
      definition of this malformation.

PMID- 18824498
TI  - Changing use of surfactant over 6 years and its relationship to chronic lung
      disease.
AB  - OBJECTIVES: Our goals were to identify the trend of surfactant use over a 6-year
      period and to determine whether a relationship exists between the incidence of
      chronic lung disease in infants born weighing <1000 g who receive surfactant and
      those who do not. METHODOLOGY: Data regarding surfactant use, incidence of
      chronic lung disease, nasal continuous positive airway pressure use and duration,
      and demographic data were collected from the Alere (formerly ParadigmHealth)
      database from 2001 to 2006 (n = 3086). Groups were compared by using chi(2) test,
      analysis of variance, or Student's t test. RESULTS: Use of surfactant has
      decreased over time from 67% in 2001 to 59.9% in 2006. Infants who received
      surfactant were more likely to develop chronic lung disease. Those who received
      >1 dose of surfactant were more likely to develop chronic lung disease when
      compared with infants treated with only 1 dose. Chronic lung disease rates have
      risen over time from 47.8% in 2001 to 57.8% in 2006. There was no difference in
      survival between groups. CONCLUSIONS: Despite the findings that surfactant use
      decreased during the study period and the rate of chronic lung disease increased,
      the data do not support a connection. Infants who receive surfactant are more
      likely to develop chronic lung disease, and chronic lung disease rates are stable
      in those infants not treated with surfactant. It is concerning, however, that 60%
      of infants not receiving surfactant developed chronic lung disease.

PMID- 18824499
TI  - Long-term outcome prediction by clinicopathological risk classification
      algorithms in node-negative breast cancer--comparison between Adjuvant!, St
      Gallen, and a novel risk algorithm used in the prospective randomized Node
      Negative-Breast Cancer-3 (NNBC-3) trial.
AB  - BACKGROUND: Defining risk categories in breast cancer is of considerable clinical
      significance. We have developed a novel risk classification algorithm and
      compared its prognostic utility to the Web-based tool Adjuvant! and to the St
      Gallen risk classification. PATIENTS AND METHODS: After a median follow-up of 10
      years, we retrospectively analyzed 410 consecutive node-negative breast cancer
      patients who had not received adjuvant systemic therapy. High risk was defined by
      any of the following criteria: (i) age <35 years, (ii) grade 3, (iii) human
      epithelial growth factor receptor-2 positivity, (iv) vascular invasion, (v)
      progesterone receptor negativity, (vi) grade 2 tumors >2 cm. All patients were
      also characterized using Adjuvant! and the St Gallen 2007 risk categories. We
      analyzed disease-free survival (DFS) and overall survival (OS). RESULTS: The Node
      Negative-Breast Cancer-3 (NNBC-3) algorithm enlarged the low-risk group to 37% as
      compared with Adjuvant! (17%) and St Gallen (18%), respectively. In multivariate
      analysis, both Adjuvant! [P = 0.027, hazard ratio (HR) 3.81, 96% confidence
      interval (CI) 1.16-12.47] and the NNBC-3 risk classification (P = 0.049, HR 1.95,
      95% CI 1.00-3.81) significantly predicted OS, but only the NNBC-3 algorithm
      retained its prognostic significance in multivariate analysis for DFS (P <
      0.0005). CONCLUSION: The novel NNBC-3 risk algorithm is the only
      clinicopathological risk classification algorithm significantly predicting DFS as
      well as OS.

PMID- 18824500
TI  - Venous vascular malformations of the craniofacial region: pre-operative
      embolisation with direct percutaneous puncture and N-butyl cyanoacrylate.
AB  - Craniofacial venous vascular malformations cause severe cosmetic problems and yet
      these lesions are not candidates for transcatheter embolisation owing to the lack
      of arterial feeders. The purpose of this study was to evaluate the effectiveness
      of pre-operative embolisation of these lesions with N-butyl 2-cyanoacrylate
      (NBCA) via direct puncture. Between September 2003 and April 2006, 13 patients (7
      female; age range, 6-64 years; mean, 16.7 years) were embolised with direct
      puncture and injection of NBCA. All of the patients were referred from plastic
      surgery with an operational plan. Angiography performed in all patients showed no
      or little arterial staining. NBCA diluted with iodized oil at a ratio of 1:6
      (18%) was injected via a percutaneously placed 21 gauge needle. Complete
      embolisation was achieved in 8 patients and partial embolisation in the remaining
      5. A total of 18 sessions of embolisation were performed on 13 patients. Nine
      patients underwent only one embolisation session, three patients underwent two
      sessions and only one patient underwent three sessions. The mean volume of NBCA
      used per session was 5.8 ml, ranging from 1-12 ml. All patients underwent a
      successful surgical resection to improve cosmetic disfigurement within 10-15 days
      after the embolisation procedure. Mean follow-up time was 22 months. One patient
      experienced skin necrosis on her nose after embolisation. No other complications
      related to the procedure were observed. In conclusion, pre-operative NBCA
      embolisation with direct puncture is a safe and easy procedure. It can increase
      the success of the surgical treatment of these lesions.

PMID- 18824501
TI  - Patient experiences of colonoscopy, barium enema and CT colonography: a
      qualitative study.
AB  - Previous studies of patient experience with bowel screening tests, in particular
      CT colonography (CTC), have superimposed global rating scales and not explored
      individual experience in detail. To redress this, we performed qualitative
      interviews in order to characterize patient expectations and experiences in
      depth. Following ethical permission, 16 patients undergoing CTC, 18 undergoing
      colonoscopy and 15 undergoing barium enema agreed to a semi-structured interview
      by a health psychologist. Interviews were recorded, responses transcribed and
      themes extracted with the aim of assimilating individual experiences to
      facilitate subsequent development and interpretation of quantitative surveys of
      overall satisfaction with each diagnostic test. Transcript analysis identified
      three principal themes: physical sensations, social interactions and information
      provision. Physical sensations differed for each test but were surprisingly well
      tolerated overall. Social interactions with staff were perceived as very
      important in colouring the whole experience, particularly in controlling the
      feelings of embarrassment, which was critical for all procedures. Information
      provision was also an important determinant of experience. Verbal feedback was
      most common during colonoscopy and invariably reassuring. However, patients
      undergoing CTC received little visual or verbal feedback and were often confused
      regarding the test outcome. Barium enema had no specific advantage over other
      tests. Qualitative interviews provided important perspectives on patient
      experience. Our data demonstrated that models describing the quality of medical
      encounters are applicable to single diagnostic episodes. Staff interactions and
      information provision were particularly important. We found advantages specific
      to both CTC and colonoscopy but none for barium enema. CTC could benefit greatly
      from improved information provision following examination.

PMID- 18824502
TI  - A dose distribution overlay technique for image guidance during prostate
      radiotherapy.
AB  - Adaptive radiotherapy involves altering the treatment plan according to
      variations in patient anatomy and set-up. This relies upon an accurate
      representation of the changing dose distribution within the patient, requiring a
      full dose recalculation. This work proposes a novel workflow using the planned
      dose distribution to assess dose coverage in three-dimensional verification CT
      studies acquired at the time of treatment delivery, using an overlay technique,
      in lieu of a recalculated dose distribution. The concept has been validated in a
      pilot study of 10 patients, each with 7-10 on-treatment CT studies. Differences
      between the geometric shape of the treatment plans for the 95% isodose and the
      95% isodose obtained when the planned geometry was recalculated from the
      verification CT dataset were quantified. Dosimetric coverage of the verification
      clinical target volume (vCTV) was assessed for both the proposed overlay
      technique and the recalculated "delivered" dose distribution, and the conclusions
      on adequacy were compared. Results were consistent with geometric uncertainties
      of the dose calculation matrix (5 x 5 x 5 mm), suggesting that differences in the
      geometric shape of the 95% isodose are not significant for normal variations in
      patients' anatomy. Decisions on adequacy of vCTV coverage were consistent in 80
      out of 87 cases, with discrepancies limited to a maximum of three axial slices
      per study within the range 0.5-4.5 mm (mean, 1.6 mm). The proposed dosimetric
      overlay technique has been validated and found to be an acceptable method of
      image-guided radiotherapy of the prostate suitable for effective implementation
      in the treatment clinic.

PMID- 18824503
TI  - The conduit system of the lymph node.
AB  - The lymphoid compartment of lymph nodes is impermeable to many molecules that are
      delivered via afferent lymphatic vessels. In the lymphoid compartment, fibroblast
      reticular cells form an interconnected network-the conduit system. This network
      has a structural function supporting tightly packed lymphocytes and antigen
      presenting cells; however, it also has an important function as a molecular
      sieve, since it contains tubules that are the only entry point for fluid and
      allow only small molecules and particles (including antigens) to flow along the
      network. This size exclusion may prevent pathogens entering the blood from lymph.
      Dendritic cells can sample antigens from the conduit system and present them to
      nearby lymphocytes; this may be particularly important in initiating immune
      responses. The importance of larger antigen transport via macrophages or other
      cells is unclear. Lymphocytes and antigen-presenting dendritic cells actively
      move and interact along the conduit system, perhaps in response to chemokines or
      cytokines transported by the conduit system; these molecules may also be
      transported to high endothelial venules and regulate the attraction of blood
      leukocytes to the lymph nodes. The conduit system is also important for fluid
      distribution between afferent lymphatics and blood, but the mechanisms are not
      yet established.

PMID- 18824504
TI  - Deliberately provoking local inflammation drives tumors to become their own
      protective vaccine site.
AB  - Anti-cancer immunotherapies aim to generate resolution of all existing tumors,
      including inaccessible ones, and provide long-term protection against recurrence.
      This is rarely achieved. Thus, we aimed to determine if the tumor
      microenvironment could be turned into a potent 'self'-vaccine site. Our target
      was to eradicate larger tumor burdens. Our models respond to single-agent
      immunotherapies; however, they fail at a precisely defined 'cut-off' tumor
      burden. Thus, this system was used to define the immune mechanisms required to
      mediate regression of larger tumors that are resistant to mono-immunotherapies.
      We report that direct injection of IL-2 with agonist anti-CD40 antibody into the
      tumor bed resulted in permanent resolution of treated and untreated distal
      tumors. Tumor-infiltrating CD8(+) T cells and neutrophils collaborated to
      eradicate treated tumors, IFNgamma was not critical and protective memory was
      preserved. This approach relied only on tumor antigens expressed within the tumor
      microenvironment. It also avoided systemic toxicities, did not require
      chemotherapy or surgery and is clinically useful because only one tumor site has
      to be accessible for treatment. We conclude that provoking intra-tumoral
      inflammation skews the tumor microenvironment from tumorigenic to immunogenic,
      resulting in the resolution of treated and untreated distal tumors, as well long
      term protective memory.

PMID- 18824505
TI  - Post-transcriptional regulation of auxin transport proteins: cellular
      trafficking, protein phosphorylation, protein maturation, ubiquitination, and
      membrane composition.
AB  - Auxin concentration gradients, established by polar transport of auxin, are
      essential for the establishment and maintenance of polar growth and morphological
      patterning. Three families of cellular transport proteins, PIN-formed (PIN), P
      glycoprotein (ABCB/PGP), and AUXIN RESISTANT 1/LIKE AUX1 (AUX1/LAX), can
      independently and co-ordinately transport auxin in plants. Regulation of these
      proteins involves intricate and co-ordinated cellular processes, including
      protein-protein interactions, vesicular trafficking, protein phosphorylation,
      ubiquitination, and stabilization of the transporter complexes on the plasma
      membrane.

PMID- 18824506
TI  - The IkappaBalpha/NF-kappaB complex has two hot spots, one at either end of the
      interface.
AB  - IkappaBalpha binds to and inhibits the transcriptional activity of NF-kappaB
      family members via its ankyrin repeat (AR) domain. The binding affinity of
      IkappaBalpha with NF-kappaB(p50/p65) heterodimers and NF-kappaB(p65/65)
      homodimers is in the picomolar range, and in the cell, this results in long half
      lives of the complexes. Direct binding experiments have been performed using
      surface plasmon resonance (SPR) and isothermal titration calorimetry (ITC) on a
      series of truncations and mutations in order to understand what regions of the
      interface are most important for the tight binding affinity of this complex. We
      previously showed that interactions between residues 305 and 321 of NF
      kappaB(p65) with the first AR of IkappaBalpha are critical for the binding
      energy. Interactions in this region are responsible for more than 7 kcal/mol of
      the binding energy. Here we show equally drastic consequences for the binding
      energy occur upon truncation of even a few residues at the C terminus of
      IkappaBalpha. Thus, the interface actually has two hot spots, one at either end
      of the elongated and large surface of interaction. These results suggest a
      "squeeze" mechanism that leads to the extremely high affinity of the
      IkappaBalpha*NF-kappaB complex through stabilization of the ankyrin repeat
      domain.

PMID- 18824507
TI  - Unconventional serine proteases: variations on the catalytic Ser/His/Asp triad
      configuration.
AB  - Serine proteases comprise nearly one-third of all known proteases identified to
      date and play crucial roles in a wide variety of cellular as well as
      extracellular functions, including the process of blood clotting, protein
      digestion, cell signaling, inflammation, and protein processing. Their hallmark
      is that they contain the so-called "classical" catalytic Ser/His/Asp triad.
      Although the classical serine proteases are the most widespread in nature, there
      exist a variety of "nonclassical" serine proteases where variations to the
      catalytic triad are observed. Such variations include the triads Ser/His/Glu,
      Ser/His/His, and Ser/Glu/Asp, and include the dyads Ser/Lys and Ser/His. Other
      variations are seen with certain serine and threonine peptidases of the Ntn
      hydrolase superfamily that carry out catalysis with a single active site residue.
      This work discusses the structure and function of these novel serine proteases
      and threonine proteases and how their catalytic machinery differs from the
      prototypic serine protease class.

PMID- 18824508
TI  - The interaction of CK2alpha and CK2beta, the subunits of protein kinase CK2,
      requires CK2beta in a preformed conformation and is enthalpically driven.
AB  - The protein kinase CK2 (former name: "casein kinase 2") predominantly occurs as a
      heterotetrameric holoenzyme composed of two catalytic chains (CK2alpha) and two
      noncatalytic subunits (CK2beta). The CK2beta subunits form a stable dimer to
      which the CK2alpha monomers are attached independently. In contrast to the
      cyclins in the case of the cyclin-dependent kinases CK2beta is no on-switch of
      CK2alpha; rather the formation of the CK2 holoenzyme is accompanied with an
      overall change of the enzyme's profile including a modulation of the substrate
      specificity, an increase of the thermostability, and an allocation of docking
      sites for membranes and other proteins. In this study we used C-terminal deletion
      variants of human CK2alpha and CK2beta that were enzymologically fully competent
      and in particular able to form a heterotetrameric holoenzyme. With differential
      scanning calorimetry (DSC) we confirmed the strong thermostabilization effect of
      CK2alpha on CK2beta with an upshift of the CK2alpha melting temperature of more
      than 9 degrees . Using isothermal titration calorimetry (ITC) we measured a
      dissociation constant of 12.6 nM. This high affinity between CK2alpha and CK2beta
      is mainly caused by enthalpic rather than entropic contributions. Finally, we
      determined a crystal structure of the CK2beta construct to 2.8 A resolution and
      revealed by structural comparisons with the CK2 holoenzyme structure that the
      CK2beta conformation is largely conserved upon association with CK2alpha, whereas
      the latter undergoes significant structural adaptations of its backbone.

PMID- 18824509
TI  - Analysis and classification of RNA tertiary structures.
AB  - There is a fast growing interest in noncoding RNA transcripts. These transcripts
      are not translated into proteins, but play essential roles in many cellular and
      pathological processes. Recent efforts toward comprehension of their function has
      led to a substantial increase in both the number and the size of solved RNA
      structures. With the aim of addressing questions relating to RNA structural
      diversity, we examined RNA conservation at three structural levels: primary,
      secondary, and tertiary structure. Additionally, we developed an automated method
      for classifying RNA structures based on spatial (three-dimensional [3D])
      similarity. Applying the method to all solved RNA structures resulted in a
      classified database of RNA tertiary structures (DARTS). DARTS embodies 1333
      solved RNA structures classified into 94 clusters. The classification is
      hierarchical, reflecting the structural relationship between and within clusters.
      We also developed an application for searching DARTS with a new structure. The
      search is fast and its performance was successfully tested on all solved RNA
      structures since the creation of DARTS. A user-friendly interface for both the
      database and the search application is available online. We show intracluster and
      intercluster similarities in DARTS and demonstrate the usefulness of the search
      application. The analysis reveals the current structural repertoire of RNA and
      exposes common global folds and local tertiary motifs. Further study of these
      conserved substructures may suggest possible RNA domains and building blocks.
      This should be beneficial for structure prediction and for gaining insights into
      structure-function relationships.

PMID- 18824510
TI  - Characterization of the termination-reinitiation strategy employed in the
      expression of influenza B virus BM2 protein.
AB  - Coupled expression of the M1 and BM2 open-reading frames (ORFs) of influenza B
      from the dicistronic segment 7 mRNA occurs by a process of termination-dependent
      reinitiation. The AUG start codon of the BM2 ORF overlaps the stop codon of the
      upstream M1 ORF in the pentanucleotide UAAUG, and BM2 synthesis is dependent upon
      translation of the M1 ORF and termination at the stop codon. Here, we have
      investigated the mRNA sequence requirements for BM2 expression. Termination
      reinitiation is dependent upon 45 nucleotide (nt) of RNA immediately upstream of
      the UAAUG pentanucleotide, which includes an essential stretch complementary to
      18S rRNA helix 26. Thus, similar to the caliciviruses, base-pairing between mRNA
      and rRNA is likely to play a role in tethering the 40S subunit to the mRNA
      following termination at the M1 stop codon. Consistent with this, repositioning
      of the M1 stop codon more than 24 nt downstream from the BM2 start codon
      inhibited BM2 expression. RNA structure probing revealed that the RNA upstream of
      the UAAUG overlap is not highly structured, but upon encountering the M1 stop
      codon by the ribosome, a stem-loop may form immediately 5' of the ribosome, with
      the 18S rRNA complementary region in the apical loop and in close proximity to
      helix 26. Mutational analysis reveals that the normal requirements for start site
      selection in BM2 expression are suspended, with little effect of initiation codon
      context and efficient use of noncanonical initiation codons. This suggests that
      the full complement of initiation factors is not required for the reinitiation
      process.

PMID- 18824511
TI  - A novel biochemical method to identify target genes of individual microRNAs:
      identification of a new Caenorhabditis elegans let-7 target.
AB  - MicroRNAs (miRNAs) are roughly 22-nucleotide regulatory RNAs that play important
      roles in many developmental and physiological processes. Animal miRNAs down
      regulate target genes by forming imperfect base pairs with 3' untranslated
      regions (3' UTRs) of their mRNAs. Thousands of miRNAs have been discovered in
      several organisms. However, the target genes of almost all of these miRNAs remain
      to be identified. Here, we describe a method for isolating cDNA clones of target
      mRNAs that form base pairs in vivo with an endogenous miRNA of interest, in which
      the cDNAs are synthesized from the mRNAs using the miRNA as a reverse
      transcription primer. The application of this method to Caenorhabditis elegans
      miRNA lin-4 under test conditions yielded many clones of the known target gene
      lin-14 that correspond to partial sequences 5' to lin-4 binding sites in the 3'
      UTR. The method was also applied to C. elegans miRNA let-7 and a new target gene
      responsible for the lethal phenotype in let-7 mutants was identified. These
      results demonstrate that the method is a useful way to identify targets on the
      basis of base pairing with individual miRNAs.

PMID- 18824512
TI  - The 3' proximal translational enhancer of Turnip crinkle virus binds to 60S
      ribosomal subunits.
AB  - During cap-dependent translation of eukaryotic mRNAs, initiation factors interact
      with the 5' cap to attract ribosomes. When animal viruses translate in a cap
      independent fashion, ribosomes assemble upstream of initiation codons at internal
      ribosome entry sites (IRES). In contrast, many plant viral genomes do not contain
      5' ends with substantial IRES activity but instead have 3' translational
      enhancers that function by an unknown mechanism. A 393-nucleotide (nt) region
      that includes the entire 3' UTR of the Turnip crinkle virus (TCV) synergistically
      enhances translation of a reporter gene when associated with the TCV 5' UTR. The
      major enhancer activity was mapped to an internal region of approximately 140 nt
      that partially overlaps with a 100-nt structural domain previously predicted to
      adopt a form with some resemblance to a tRNA, according to a recent study by J.C.
      McCormack and colleagues. The T-shaped structure binds to 80S ribosomes and 60S
      ribosomal subunits, and binding is more efficient in the absence of surrounding
      sequences and in the presence of a pseudoknot that mimics the tRNA-acceptor stem.
      Untranslated TCV satellite RNA satC, which contains the TCV 3' end and 6-nt
      differences in the region corresponding to the T-shaped element, does not
      detectably bind to 80S ribosomes and is not predicted to form a comparable
      structure. Binding of the TCV T-shaped element by 80S ribosomes was unaffected by
      salt-washing, reduced in the presence of AcPhe-tRNA, which binds to the P-site,
      and enhanced binding of Phe-tRNA to the ribosome A site. Mutations that reduced
      translation in vivo had similar effects on ribosome binding in vitro. This strong
      correlation suggests that ribosome entry in the 3' UTR is a key function of the
      3' translational enhancer of TCV and that the T-shaped element contains some tRNA
      like properties.

PMID- 18824513
TI  - Mutational analysis of the U12-dependent branch site consensus sequence.
AB  - Highly conserved sequences at the 5' splice site and branch site of U12-dependent
      introns are important determinants for splicing by U12-dependent spliceosomes.
      This study investigates the in vivo splicing phenotypes of mutations in the
      branch site consensus sequence of the U12-dependent intron F from a human NOL1
      (P120) minigene. Intron F contains a fully consensus branch site sequence
      (UUCCUUAAC). Mutations at each position were analyzed for their effects on U12
      dependent splicing in vivo. Mutations at most positions resulted in a significant
      reduction of correct U12-dependent splicing. Defects observed included increased
      unspliced RNA levels, the activation of cryptic U2-dependent 5' and 3' splice
      sites, and the activation of cryptic U12-dependent branch/3' splice sites. A
      strong correlation was observed between the predicted thermodynamic stability of
      the branch site: U12 snRNA interaction and correct U12-dependent splicing. The
      lack of a polypyrimidine tract between the branch site and 3' splice site of U12
      dependent introns and the observed reliance on base-pairing interactions for
      correct U12-dependent splicing emphasize the importance of RNA/RNA interactions
      during U12-dependent intron recognition and proper splice site selection.

PMID- 18824514
TI  - Kinetic and thermodynamic studies of peptidyltransferase in ribosomes from the
      extreme thermophile Thermus thermophilus.
AB  - Throughout evolution, emerging organisms survived by adapting existing
      biochemical processes to new reaction conditions. Simple protein enzymes balanced
      changes in structural stability with changes that permitted optimal catalysis by
      adjustments in both entropic and enthalpic contributions to the free energy of
      activation for the reaction. Study of adaptive mechanisms by large multicomponent
      enzymes such as the ribosome has been largely unexplored. Here we have determined
      the kinetic and thermodynamic parameters of peptidyltransferase in ribosomes from
      the extreme thermophile Thermus thermophilus. Activity of thermophilic enzymes
      can be assayed over a wide range of temperatures, enabling one to measure
      accurate catalytic rates and determine enthalpic and entropic contributions to
      the free energy of activation of the reaction. Differences in the reaction
      conditions used here and in published studies on mesophilic ribosomes prevent
      direct comparison, but our data on Thermus ribosomes suggest that these ribosomes
      have adapted to changing environments using the same strategies as simple protein
      enzymes, balancing stability and flexibility without loss of catalytic rate. This
      strategy must be a very ancient process, perhaps first used by primitive
      ribosomes in the RNA World.

PMID- 18824515
TI  - Polynucleotide phosphorylase hinders mRNA degradation upon ribosomal protein S1
      overexpression in Escherichia coli.
AB  - The exoribonuclease polynucleotide phosphorylase (PNPase, encoded by pnp) is a
      major player in bacterial RNA decay. In Escherichia coli, PNPase expression is
      post-transcriptionally regulated at the level of mRNA stability. The primary
      transcript is very efficiently processed by the endonuclease RNase III at a
      specific site and the processed pnp mRNA is rapidly degraded in a PNPase
      dependent manner. While investigating the PNPase autoregulation mechanism we
      found, by UV-cross-linking experiments, that the ribosomal protein S1 in crude
      extracts binds to the pnp-mRNA leader region. We assayed the potential role of S1
      protein in pnp gene regulation by modulating S1 expression from depletion to
      overexpression. We found that S1 depletion led to a sharp decrease of the amount
      of pnp and other tested mRNAs, as detected by Northern blotting, whereas S1
      overexpression caused a strong stabilization of pnp and the other transcripts.
      Surprisingly, mRNA stabilization depended on PNPase, as it was not observed in a
      pnp deletion strain. PNPase-dependent stabilization, however, was not detected by
      chemical decay assay of bulk mRNA. Overall, our data suggest that PNPase
      exonucleolytic activity may be modulated by the translation potential of the
      target mRNAs and that, upon ribosomal protein S1 overexpression, PNPase protects
      from degradation a set of full-length mRNAs. It thus appears that a single mRNA
      species may be differentially targeted to either decay or PNPase-dependent
      stabilization, thus preventing its depletion in conditions of fast turnover.

PMID- 18824516
TI  - Exonucleolysis is required for nuclear mRNA quality control in yeast THO mutants.
AB  - Production of aberrant messenger ribonucleoprotein particles (mRNPs) is subject
      to quality control (QC). In yeast strains carrying mutations of the THO complex,
      transcription induction triggers a number of interconnected QC phenotypes: (1)
      rapid degradation of several mRNAs; (2) retention of a fraction of THO-dependent
      mRNAs in transcription site-associated foci; and (3) formation of a high
      molecular weight DNA/protein complex in the 3'-ends of THO target genes. Here, we
      demonstrate that the 3'-5' exonucleolytic domain of the nuclear exosome factor
      Rrp6p is necessary for establishing all QC phenotypes associated with THO
      mutations. The N terminus of Rrp6p is also important presumably through its
      binding to the Rrp6p co-factor Rrp47p. Interestingly, the 3'-5' exonucleolytic
      activity of Dis3p, the only other active exonuclease of the nuclear exosome, can
      also contribute to RNA QC in THO mutants, while other nuclear 3'-5' exonucleases
      cannot. Our data show that exonucleolytic attack by the nuclear exosome is needed
      both for provoking mRNP QC and for its ensuing elimination of faulty RNA.

PMID- 18824517
TI  - Generalized linear models with unspecified reference distribution.
AB  - We propose a new class of semiparametric generalized linear models. As with
      existing models, these models are specified via a linear predictor and a link
      function for the mean of response Y as a function of predictors X. Here, however,
      the "baseline" distribution of Y at a given reference mean mu(0) is left
      unspecified and is estimated from the data. The response distribution when the
      mean differs from mu(0) is then generated via exponential tilting of the baseline
      distribution, yielding a response model that is a natural exponential family,
      with corresponding canonical link and variance functions. The resulting model has
      a level of flexibility similar to the popular proportional odds model. Maximum
      likelihood estimation is developed for response distributions with finite
      support, and the new model is studied and illustrated through simulations and
      example analyses from aging research.

PMID- 18824518
TI  - Role for sphingosine kinase 1 in colon carcinogenesis.
AB  - Sphingosine kinase 1 (SphK1) phosphorylates sphingosine to form sphingosine-1
      phosphate (S1P) and is a critical regulator of sphingolipid-mediated functions.
      Cell-based studies suggest a tumor-promoting function for the SphK1/S1P pathway.
      Also, our previous studies implicated the SphK1/S1P pathway in the induction of
      the arachidonic acid cascade, a major inflammatory pathway involved in colon
      carcinogenesis. Therefore, we investigated whether the SphK1/S1P pathway is
      necessary for mediating carcinogenesis in vivo. Here, we report that 89% (42/47)
      of human colon cancer samples stained positively for SphK1, whereas normal colon
      mucosa had negative or weak staining. Adenomas had higher expression of SphK1 vs.
      normal mucosa, and colon cancers with metastasis had higher expression of SphK1
      than those without metastasis. In the azoxymethane (AOM) murine model of colon
      cancer, SphK1 and S1P were significantly elevated in colon cancer tissues
      compared to normal mucosa. Moreover, blood levels of S1P were higher in mice with
      colon cancers than in those without cancers. Notably, SphK1(-/-) mice subjected
      to AOM had significantly less aberrant crypt foci (ACF) formation and
      significantly reduced colon cancer development. These results are the first in
      vivo evidence that the SphK1/S1P pathway contributes to colon carcinogenesis and
      that inhibition of this pathway is a potential target for chemoprevention.

PMID- 18824519
TI  - Opposing effects of ERK and p38-JNK MAP kinase pathways on formation of prions in
      GT1-1 cells.
AB  - Brain-derived neurotrophic factor, which activates the extracellular regulated
      kinase (ERK) pathway, increases formation of prions in scrapie-infected
      gonadotropin-releasing hormone (GT1-1) cells. This indicates that conversion of
      the cellular prion protein PrP(C) to its pathogenic isoform, PrP(Sc), can be
      regulated by physiological stimuli acting on specific signal transduction
      pathways. In the present study, we examined the involvement of different mitogen
      activated protein (MAP) kinase cascades and the cAMP-PKA pathway in formation of
      proteinase K-resistant PrP(Sc) (rPrP(Sc)). Long-term depolarization of GT1-1
      cells infected with the Rocky Mountain Laboratory strain of scrapie increased the
      formation of rPrP(Sc). This effect was associated to ERK activation and was
      blocked by the MAPK/ERK kinase (MEK) inhibitor U0126. Treatment with forskolin
      caused a similar increase in rPrP(Sc) formation that was prevented by the protein
      kinase A (PKA) inhibitor H89. Both depolarization and forskolin treatment were
      accompanied by increased phosphorylation of the S6 ribosomal protein, while
      phosphorylation of histone H3 occurred only after forskolin treatment. Inhibitors
      of p38- and c-Jun NH(2)-terminal kinase (JNK) promoted the formation of rPrP(Sc),
      in contrast to the clearance of rPrP(Sc) produced by inhibitors of the ERK
      pathway. Thus, the ERK and the p38-JNK MAP kinase pathways appear to exert
      opposing effects on rPrP(Sc) formation, suggesting that balances between these
      intracellular signaling cascades may regulate replication of prions.

PMID- 18824520
TI  - Diurnal variation in phagocytic activity of splenic phagocytes in freshwater
      teleost Channa punctatus: melatonin and its signaling mechanism.
AB  - The aim of the present study was to understand the rhythmic changes in innate
      immune response in freshwater fish Channa punctatus. Furthermore, the putative
      role of melatonin as the zeitgeber was explored. The phagocytic activity of
      splenic phagocytes assessed at 6-h intervals showed higher phagocytic activity
      during light phase than dark phase. The increased phagocytic activity during
      light phase was diminished by melatonin administration at 09:00 h. Implication of
      melatonin in control of diurnal variation in phagocytic activity was
      substantiated by administering irreversible tryptophan hydroxylase inhibitor,
      para-chlorophenylalanine (pCPA) at 18:00 h. pCPA abrogated the decrease of
      phagocytosis observed during dark phase, and the same was restored after
      melatonin administration. The direct involvement of melatonin in modulation of
      phagocytosis was demonstrated following in vitro experiments. Melatonin
      suppressed the phagocytic activity in a concentration-dependent manner without
      affecting the viability of phagocytes. The existence of functional membrane-bound
      melatonin receptors on fish phagocytes was pharmacologically demonstrated.
      Luzindole, melatonin membrane receptor antagonist, completely blocked the
      inhibitory effect of melatonin on phagocytosis. Further receptor-coupled
      adenylate cyclase-protein kinase A (PKA) pathway was implicated in transducing
      the melatonin effect as both adenylate cyclase and PKA inhibitor completely
      nullified the melatonin-induced suppression. An increased intracellular cAMP
      level in response to melatonin ascertained the second messenger status of cAMP
      for downstream signaling. However, manipulation of phospholipase C/PKC failed to
      influence the effect of melatonin on phagocytic activity. These observations in
      C. punctatus evidenced the diurnal rhythmicity in phagocytic activity that is
      regulated by melatonin following membrane-bound receptor-coupled cAMP-PKA
      pathway.

PMID- 18824521
TI  - Regulation of prostaglandin biosynthesis by interleukin-1 in cultured bovine
      endometrial cells.
AB  - Interleukin-1 (IL1) has been shown to be a potent stimulator of prostaglandin
      (PG) production in bovine endometrium. The aim of the present study was to
      determine the cell types in the endometrium (epithelial or stromal cells)
      responsible for the secretion of PGE2 and PGF2alpha in response to IL1A, and the
      intracellular mechanisms of IL1A action. Cultured bovine epithelial and stromal
      cells were exposed to IL1A or IL1B (0.006-3.0 nM) for 24 h. IL1A and IL1B dose
      dependently stimulated PGE2 and PGF2alpha production in the stromal cells, but
      not in the epithelial cells. The stimulatory effect of IL1A (0.06-3.0 nM) on PG
      production was greater than that of IL1B. The stimulatory actions of IL1A on PG
      production was augmented by supplementing arachidonic acid (AA). When the stromal
      cells were incubated with IL1A and inhibitors of phospholipase (PL) C or PLA2 (1
      microM; anthranilic acid), only PLA2 inhibitor completely stopped the stimulatory
      action of IL1A on PG production. Moreover, a specific cyclooxygenase-2 (COX2)
      inhibitor blocked the stimulatory effect of IL1A on PG production. IL1A (0.06 nM)
      promoted COX2 and microsomal PGE synthase-1 (PGES1) gene and its protein
      expression. The expression of COX1, PGES2, PGES3, and PGF synthase (PGFS) mRNA
      was not affected by IL1A in the stromal cells. The overall results indicate that
      1) the target of IL1A and IL1B for stimulating both PGE2 and PGF2alpha production
      is the stromal cells, 2) IL1A is a far more potent stimulator than IL1B on PG
      production in stromal cells, 3) the stimulatory effect of IL1A on PG production
      is mediated via the activation of PLA2 and COX2, and (4) IL1A induced PG
      production by increasing expressions of COX2 and PGES1 mRNAs and their proteins
      in bovine stromal cells.

PMID- 18824522
TI  - A null allele impairs function of CYP2C76 gene in cynomolgus monkeys: a possible
      genetic tool for generation of a better animal model in drug metabolism.
AB  - The monkey CYP2C76 gene does not correspond to any of the human CYP2C genes, and
      its enzyme is at least partly responsible for the species difference occasionally
      seen in drug metabolism between monkeys and humans. To establish a line and/or
      lines of monkeys that are expected to show metabolic patterns highly similar to
      humans, we set out to find monkeys that lacked CYP2C76 activity. By genetic
      screening of 73 monkeys and a database search of expressed sequence tags, we
      found a total of 10 nonsynonymous genetic variants in the coding region of
      CYP2C76, including a null genotype (c.449TG>A). Some of the variants were
      differently distributed between two animal groups originating from different
      geographical regions (Indochina and Indonesia). After screening 170 additional
      genomic samples, we identified a total of eight animals (six males and two
      females) that were heterozygous for c.449TG>A, which could be used for
      establishing a homozygous line. If the homozygotes show drug-metabolizing
      properties more similar to humans than wild-type monkeys, the homozygotes may
      serve as a better animal model for drug metabolism. The data presented in this
      article provide the essential genetic information to perform a successful study
      by using cynomolgus monkeys and present a possible tool to generate a better
      animal model for drug metabolism.

PMID- 18824523
TI  - Natural allelic variants of bovine ATP-binding cassette transporter ABCG2:
      increased activity of the Ser581 variant and development of tools for the
      discovery of new ABCG2 inhibitors.
AB  - ATP-binding cassette transporter ABCG2 [breast cancer resistance protein (BCRP)]
      is a member of the ABC transporter superfamily that actively extrudes xenotoxins
      from cells and is a major determinant of the bioavailability of many compounds.
      ABCG2 expression is strongly induced during lactation in the mammary gland and is
      related to the active secretion of drugs into the milk. The presence of drug
      residues and environmental pollutants in milk is an outstanding problem for human
      milk consumption and milk industrial processes, involving important risks to
      public health and the dairy industry. In cows, a single nucleotide polymorphism
      (SNP) in this protein has been described previously (Tyr581) and is associated
      with higher fat and protein percentages and lower milk yield. However, whether
      this amino acid substitution affects ABCG2-mediated drug transport in cows,
      including milk secretion, required further exploration. We cloned the two
      variants of bovine ABCG2 and evaluated the effect of this SNP on mitoxantrone
      accumulation assays performed in ovine primary fibroblasts transiently expressing
      either of the variants. It is interesting to note that statistically significant
      differences in activity between both variants were observed, and the Ser581
      variant was related with an increased efflux activity. In addition, we
      demonstrated that genistein is a very good inhibitor of bovine ABCG2 and
      identified new inhibitors of the transporter, such as the macrocyclic lactones,
      ivermectin, and selamectin. Moreover, the inhibitory effect of these compounds on
      human and murine ABCG2 homologs was confirmed using transduced Marbin-Dabin
      canine kidney II cells. These findings may have important implications regarding
      the presence of drug residues in milk and drug interactions affecting the
      pharmacological behavior of ABCG2 substrates.

PMID- 18824524
TI  - High-affinity interaction of sartans with H+/peptide transporters.
AB  - Sartans are very effective drugs for treatment of hypertension, heart failure,
      and other cardiovascular disorders. They antagonize the effects of angiotensin II
      at the AT(1) receptor and display p.o. bioavailability rates of 13 to 80%.
      Because some sartans sterically resemble dipeptide derivatives, we investigated
      whether they are transported by peptide transporters. We first assessed the
      effects of sartans on [(14)C]glycylsarcosine uptake into Caco-2 cells expressing
      H(+)/peptide transporter (PEPT) 1 and into SKPT cells expressing PEPT2. Losartan,
      irbesartan, valsartan, and eprosartan inhibited [glycine-1-(14)C]glycylsarcosine
      ([(14)C]Gly-Sar) uptake into Caco-2 cells in a competitive manner with K(i)
      values of 24, 230, 390, and >1000 microM. Losartan and valsartan also strongly
      inhibited the total transepithelial flux of [(14)C]Gly-Sar across Caco-2 cell
      monolayers. In SKPT cells, [(14)C]Gly-Sar uptake was inhibited with K(i) values
      of 2.2 microM (losartan), 65 microM (irbesartan), 260 microM (valsartan), and 490
      microM (eprosartan). We determined by the two-electrode voltage-clamp technique
      whether the compounds elicited transport currents by PEPT1 or PEPT2 when
      expressed in Xenopus laevis oocytes. No currents were observed for any of the
      sartans, but the compounds strongly and reversibly inhibited peptide-induced
      currents. Uptake of valsartan, losartan, and cefadroxil was quantified in HeLa
      cells after heterologous expression of human PEPT1 (hPEPT1). In contrast to
      cefadroxil, no PEPT1-specific uptake of valsartan and losartan was found. We
      conclude that the sartans tested in this study display high-affinity interaction
      with PEPTs but are not transported themselves. However, they strongly inhibit
      hPEPT1-mediated uptake of dipeptides and cefadroxil.

PMID- 18824525
TI  - The multiple depletion curves method provides accurate estimates of intrinsic
      clearance (CLint), maximum velocity of the metabolic reaction (Vmax), and
      Michaelis constant (Km): accuracy and robustness evaluated through experimental
      data and Monte Carlo simulations.
AB  - The use of multiple depletion curves for the estimation of maximum velocity of
      the metabolic reaction (V(max)), the Michaelis constant (K(m)), and intrinsic
      clearance (CL(int)) was thoroughly evaluated by means of experimental data and
      through a series of Monte Carlo simulations. The enzyme kinetics of seven
      compounds were determined using the multiple depletion curves method (MDCM), the
      traditional initial formation rate of metabolite method (IFRMM), and the "in
      vitro t(1/2)" method, and the parameter estimates that were derived from the
      three methods were compared. The impact of a change in enzyme activity during the
      incubation period on the parameter estimates and the possibility to correct for
      this were also investigated. The MDCM was in good overall agreement with the
      IFRMM. Correction for a change in enzyme activity was possible and resulted in a
      better concordance in CL(int) estimates. The robustness of the method in coping
      with different rates of substrate turnover and variable starting concentrations
      were also demonstrated through Monte Carlo simulations. Furthermore, the
      limitations imposed by assumptions inherent in the in vitro t(1/2) method were
      demonstrated both experimentally and by simulations. This study demonstrates that
      the MDCM is a robust and efficient method for estimating enzyme kinetic variables
      with high accuracy and precision. The method may potentially be used in a wide
      range of applications, from pure enzyme kinetics to in vitro-based predictions of
      the pharmacokinetics of compounds with multiple and/or unknown metabolic
      pathways.

PMID- 18824526
TI  - The CAP superfamily: cysteine-rich secretory proteins, antigen 5, and
      pathogenesis-related 1 proteins--roles in reproduction, cancer, and immune
      defense.
AB  - The cysteine-rich secretory proteins, antigen 5, and pathogenesis-related 1
      proteins (CAP) superfamily members are found in a remarkable range of organisms
      spanning each of the animal kingdoms. Within humans and mice, there are 31 and 33
      individual family members, respectively, and although many are poorly
      characterized, the majority show a notable expression bias to the reproductive
      tract and immune tissues or are deregulated in cancers. CAP superfamily proteins
      are most often secreted and have an extracellular endocrine or paracrine function
      and are involved in processes including the regulation of extracellular matrix
      and branching morphogenesis, potentially as either proteases or protease
      inhibitors; in ion channel regulation in fertility; as tumor suppressor or
      prooncogenic genes in tissues including the prostate; and in cell-cell adhesion
      during fertilization. This review describes mammalian CAP superfamily gene
      expression profiles, phylogenetic relationships, protein structural properties,
      and biological functions, and it draws into focus their potential role in health
      and disease. The nine subfamilies of the mammalian CAP superfamily include: the
      human glioma pathogenesis-related 1 (GLIPR1), Golgi associated pathogenesis
      related-1 (GAPR1) proteins, peptidase inhibitor 15 (PI15), peptidase inhibitor 16
      (PI16), cysteine-rich secretory proteins (CRISPs), CRISP LCCL domain containing 1
      (CRISPLD1), CRISP LCCL domain containing 2 (CRISPLD2), mannose receptor like and
      the R3H domain containing like proteins. We conclude that overall protein
      structural conservation within the CAP superfamily results in fundamentally
      similar functions for the CAP domain in all members, yet the diversity outside of
      this core region dramatically alters target specificity and, therefore, the
      biological consequences.

PMID- 18824527
TI  - Thiophenecarboxylate suppressor of cyclic nucleotides discovered in a small
      molecule screen blocks toxin-induced intestinal fluid secretion.
AB  - We carried out a "pathway" screen of 50,000 small molecules to identify novel
      modulators of cAMP signaling. One class of compounds, the 2-(acylamino)-3
      thiophenecarboxylates, strongly suppressed cAMP and cGMP in multiple cell lines
      in response to different agonists acting on G-protein-coupled receptors, adenylyl
      cyclase, and guanylyl cyclase. The best compounds from structure-activity
      analysis of 124 analogs, including several synthesized chiral analogs, had and
      IC(50) of <5 microM for suppression of agonist-induced cAMP and cGMP elevation.
      Measurements of cAMP, cGMP, and downstream signaling in response to various
      activators/inhibitors suggested that the 2-(acylamino)-3-thiophenecarboxylates
      function as nonselective phosphodiesterase activators, although it was not
      determined whether their action on phosphodiesterases is direct or indirect. The
      2-(acylamino)-3-thiophenecarboxylates suppressed CFTR-mediated Cl(-) current in
      T84 colonic cells in response to cholera and Escherichia coli (STa) toxins, and
      prevented intestinal fluid accumulation in a closed-loop mouse model of secretory
      diarrhea. They also prevented cyst growth in an in vitro renal epithelial cell
      model of polycystic kidney disease. The 2-(acylamino)-3-thiophenecarboxylates
      represent the first small-molecule cyclic nucleotide suppressors, whose potential
      therapeutic indications include secretory diarrheas, polycystic kidney disease,
      and growth inhibition of cAMP-dependent tumors.

PMID- 18824528
TI  - Bacteriophage 2851 is a prototype phage for dissemination of the Shiga toxin
      variant gene 2c in Escherichia coli O157:H7.
AB  - The production of Shiga toxin (Stx) (verocytotoxin) is a major virulence factor
      of Escherichia coli O157:H7 strains (Shiga toxin-producing E. coli [STEC] O157).
      Two types of Shiga toxins, designated Stx1 and Stx2, are produced in STEC O157.
      Variants of the Stx2 type (Stx2, Stx2c) are associated with high virulences of
      these strains for humans. A bacteriophage designated 2851 from a human STEC O157
      encoding the Stx2c variant was described previously. Nucleotide sequence analysis
      of the phage 2851 genome revealed 75 predicted coding sequences and indicated a
      mosaic structure typical for lambdoid phages. Analyses of free phages and K-12
      phage 2851 lysogens revealed that upon excision from the bacterial chromosome,
      the loss of a phage-encoded IS629 element leads to fusion of phage antA and antB
      genes, with the generation of a recombined antAB gene encoding a strong
      antirepressor. In wild-type E. coli O157 as well as in K-12 strains, phage 2851
      was found to be integrated in the sbcB locus. Additionally, phage 2851 carries an
      open reading frame which encodes an OspB-like type III effector similar to that
      found in Shigella spp. Investigation of 39 stx(2c) E. coli O157 strains revealed
      that all except 1 were positive for most phage 2851-specific genes and possessed
      a prophage with the same border sequences integrated into the sbcB locus. Phage
      2851-specific sequences were absent from most stx(2c)-negative E. coli O157
      strains, and we suggest that phage 2851-like phages contributed significantly to
      the dissemination of the Stx2c variant toxin within this group of E. coli.

PMID- 18824529
TI  - Experimental malaria infection triggers early expansion of natural killer cells.
AB  - In order to gain a better understanding of gene expression during early malaria
      infection, we conducted microarray analysis of early blood responses in mice
      infected with erythrocytic-stage Plasmodium chabaudi. Immediately following
      infection, we observed coordinated and sequential waves of immune responses, with
      interferon-associated gene transcripts dominating by 16 h postinfection, followed
      by strong increases in natural killer (NK) cell-associated and major
      histocompatibility complex class I-related transcripts by 32 h postinfection. We
      showed by flow cytometry that the observed elevation in NK cell-associated
      transcripts was the result of a dramatic increase in the proportion of NK cells
      in the blood during infection. Subsequent microarray analysis of NK cells
      isolated from the peripheral blood of infected mice revealed a cell proliferation
      expression signature consistent with the observation that NK cells replicate in
      response to infection. Early proliferation of NK cells was directly observed in
      studies with adoptively transferred cells in infected mice. These data indicate
      that the early response to P. chabaudi infection of the blood is marked by a
      primary wave of interferon with a subsequent response by NK cells.

PMID- 18824530
TI  - Adenoviral delivery of interleukin-10 fails to attenuate experimental Lyme
      disease.
AB  - Production of interleukin-10 (IL-10) by C57BL/6 mice following infection with
      Borrelia burgdorferi has been proposed as a mechanism whereby resistance to the
      development of experimental Lyme arthritis is maintained. In the current study,
      we sought to determine the role of IL-10 during infection of arthritis- and
      carditis-susceptible C3H mice. Infection of C3H IL-10(-/-) mice led to increased
      joint swelling and arthritis severity scores over those of wild-type C3H mice.
      Measurement of B. burgdorferi numbers in joints or disseminated tissues indicated
      a more efficient clearance of spirochetes in the absence of IL-10, similar to
      that reported in C57BL/6 IL-10(-/-) mice. However, in contrast to previous in
      vitro work, infection of C3H IL-10(-/-) mice led to decreased in vivo expression
      of the cytokines KC, IL-1beta, IL-4, and IL-12p70 in the infected joints.
      Finally, adenoviral expression of IL-10 in the infected joints of C3H mice was
      unable to modulate the development of severe Lyme arthritis and had no effect on
      spirochete clearance or Borrelia-specific antibody production. Development of
      Lyme carditis appeared to be independent of modulation by IL-10. These results
      suggest that IL-10 limits the development of joint inflammation in both arthritis
      resistant and -susceptible mouse strains infected with B. burgdorferi and that
      increased IL-10 production cannot rescue genetic susceptibility to development of
      pathology in this model.

PMID- 18824531
TI  - Regulatory T cells are locally induced during intravaginal infection of mice with
      Neisseria gonorrhoeae.
AB  - Neisseria gonorrhoeae is a gram-negative diplococcus that in human beings
      produces gonorrhea. Much clinical evidence has led to the conclusion that
      gonococcus has important mechanisms to evade host immune functions; however,
      these mechanisms are only now beginning to be elucidated. In this study, we
      determined that the BALB/c mouse is a good animal model to study gonococcus
      infection and examined the immune response against the bacteria. We determined
      that after intravaginal inoculation of mice with Neisseria gonorrhoeae, the
      bacteria reached and invaded the upper female reproductive tissues and elicited a
      T-cell-specific immune response associated with a very weak humoral response,
      altogether resembling gonococcus infection and disease in women. Remarkably, in
      the draining lymph nodes of the genital tracts of infected mice, we found an
      increase of regulatory T lymphocytes, namely, transforming growth factor beta1
      positive CD4(+) T cells and CD4(+) CD25(+) Foxp3(+) T cells. Altogether, results
      indicate that N. gonorrhoeae induces regulatory T cells, which might be related
      to the local survival of the pathogen and the establishment of a chronic
      asymptomatic infection.

PMID- 18824532
TI  - Chronic intestinal nematode infection exacerbates experimental Schistosoma
      mansoni infection.
AB  - Mixed-parasite infections are common in many parts of the world, but little is
      known of the effects of concomitant parasite infections on the immune response or
      on disease progression. We have investigated the in vivo effects of a chronic
      gastrointestinal nematode infection on the infectivity and development of the
      immune response against the common trematode helminth Schistosoma mansoni. The
      data show that mice carrying an established chronic Trichuris muris infection and
      coinfected with S. mansoni, had significantly higher S. mansoni worm burdens than
      mice without coinfection. The increase in S. mansoni worm burden was accompanied
      by a higher egg burden in the liver. Kinetic analysis of S. mansoni establishment
      indicate reduced trapping of S. mansoni larvae during skin-to-lung migration,
      with T. muris-induced alterations in lung cytokine expression and inflammatory
      foci surrounding lung-stage schistosomula, suggesting that the immunomodulatory
      effects of chronic T. muris infection elicited at the gut mucosal surface extend
      to other organs and perhaps specifically to other mucosal surfaces. The data show
      that a preexisting chronic gastrointestinal nematode infection facilitates the
      survival and migration of S. mansoni schistosomula to the portal system, and as a
      result, increases the egg burden and associated pathology of S. mansoni
      infection.

PMID- 18824533
TI  - Schistosoma mansoni antigens modulate experimental allergic asthma in a murine
      model: a major role for CD4+ CD25+ Foxp3+ T cells independent of interleukin-10.
AB  - In areas where schistosomiasis is endemic, a negative correlation is observed
      between atopy and helminth infection, associated with a low prevalence of asthma.
      We investigated whether Schistosoma mansoni infection or injection of parasite
      eggs can modulate airway allergic inflammation in mice, examining the mechanisms
      of such regulation. We infected BALB/c mice with 30 S. mansoni cercariae or
      intraperitoneally injected 2,500 schistosome eggs, and experimental asthma was
      induced by ovalbumin (OVA). The number of eosinophils in bronchoalveolar lavage
      fluid was higher in the asthmatic group than in asthmatic mice infected with S.
      mansoni or treated with parasite eggs. Reduced Th2 cytokine production,
      characterized by lower levels of interleukin-4 (IL-4), IL-5, and immunoglobulin
      E, was observed in both S. mansoni-treated groups compared to the asthmatic
      group. There was a reduction in the number of inflammatory cells in lungs of S.
      mansoni-infected and egg-treated mice, demonstrating that both S. mansoni
      infection and the egg treatment modulated the lung inflammatory response to OVA.
      Only allergic animals that were treated with parasite eggs had increased numbers
      of CD4(+) CD25(+) Foxp3(+) T cells and increased levels of IL-10 and decreased
      production of CCL2, CCL3, and CCL5 in the lungs compared to the asthmatic group.
      Neutralization of IL-10 receptor or depletion of CD25(+) T cells in vivo
      confirmed the critical role of CD4(+) CD25(+) Foxp3(+) regulatory T cells in
      experimental asthma modulation independent of IL-10.

PMID- 18824534
TI  - Schistosoma mansoni egg antigen-mediated modulation of Toll-like receptor (TLR)
      induced activation occurs independently of TLR2, TLR4, and MyD88.
AB  - Unlike most pathogens, helminth parasites and their products induce strong Th2
      responses, and dendritic cells (DCs) and macrophages exposed to helminth antigens
      generally fail to produce interleukin-12. Rather, it has been shown that helminth
      products such as soluble egg antigens (SEA; a soluble extract from Schistosoma
      mansoni eggs) inhibit the activation of DCs in response to classical Toll-like
      receptor (TLR) ligands such as lipopolysaccharide or CpG. Nevertheless, recent
      work has suggested that TLR4 and/or TLR2 plays an important role in the
      recognition of helminth products by DCs and macrophages and in the development of
      Th2 responses. Using DCs derived from TLR4(-/-), TLR2(-/-), or MyD88(-/-) mice,
      we have demonstrated that the ability of SEA to modulate DC activation is MyD88
      independent and requires neither TLR4 nor TLR2. Moreover, TLR2 and TLR4 are not
      required for SEA-pulsed DCs to induce Th2 responses in naive mice.

PMID- 18824535
TI  - Modification of lipooligosaccharide with phosphoethanolamine by LptA in Neisseria
      meningitidis enhances meningococcal adhesion to human endothelial and epithelial
      cells.
AB  - The lipooligosaccharide (LOS) of Neisseria meningitidis can be decorated with
      phosphoethanolamine (PEA) at the 4' position of lipid A and at the O-3 and O-6
      positions of the inner core of the heptose II residue. The biological role of PEA
      modification in N. meningitidis remains unclear. During the course of our studies
      to elucidate the pathogenicity of the ST-2032 (invasive) meningococcal clonal
      group, disruption of lptA, the gene that encodes the PEA transferase for 4' lipid
      A, led to a approximately 10-fold decrease in N. meningitidis adhesion to four
      kinds of human endothelial and epithelial cell lines at an multiplicity of
      infection of 5,000. Complementation of the lptA gene in a Delta lptA mutant
      restored wild-type adherence. By matrix-assisted laser desorption ionization-time
      of-flight mass spectrometry analysis, PEA was lost from the lipid A of the Delta
      lptA mutant compared to that of the wild-type strain. The effect of LptA on
      meningococcal adhesion was independent of other adhesins such as pili, Opc, Opa,
      and PilC but was inhibited by the presence of capsule. These results indicate
      that modification of LOS with PEA by LptA enhances meningococcal adhesion to
      human endothelial and epithelial cells in unencapsulated N. meningitidis.

PMID- 18824536
TI  - Platelet antistaphylococcal responses occur through P2X1 and P2Y12 receptor
      induced activation and kinocidin release.
AB  - Platelets (PLTs) act in antimicrobial host defense by releasing PLT microbicidal
      proteins (PMPs) or PLT kinocidins (PKs). Receptors mediating staphylocidal
      efficacy and PMP or PK release versus isogenic PMP-susceptible (ISP479C) and 
      resistant (ISP479R) Staphylococcus aureus strains were examined in vitro.
      Isolated PLTs were incubated with ISP479C or ISP479R (PLT/S. aureus ratio range,
      1:1 to 10,000:1) in the presence or absence of a panel of PLT inhibitors,
      including P2X and P2Y receptor antagonists of increasingly narrow specificity,
      and PLT adhesion receptors (CD41, CD42b, and CD62P). PLT-to-S. aureus exposure
      ratios of > or = 10:1 yielded significant reductions in the viability of both
      strains. Results from reversed-phase high-performance liquid chromatography
      indicated that staphylocidal PLT releasates contained PMPs and PKs. At ratios
      below 10:1, the PLT antistaphylococcal efficacy relative to the intrinsic S.
      aureus PMP-susceptible or -resistant phenotype diminished. Apyrase (an agent of
      ADP degradation), suramin (a general P2 receptor antagonist), pyridoxal 5'
      phosphonucleotide derivative (a specific P2X(1) antagonist), and cangrelor (a
      specific P2Y(12) antagonist) mitigated the PLT staphylocidal response against
      both strains, correlating with reduced levels of PMP and PK release. Specific
      inhibition occurred in the presence and absence of homologous plasma. The
      antagonism of the thromboxane A(2), cyclooxygenase-1/cyclooxygenase-2, or
      phospholipase C pathway or the hindrance of surface adhesion receptors failed to
      impede PLT anti-S. aureus responses. These results suggest a multifactorial PLT
      anti-S. aureus response mechanism involving (i) a PLT-to-S. aureus ratio
      sufficient for activation; (ii) the ensuing degranulation of PMPs, PKs, ADP,
      and/or ATP; (iii) the activation of P2X(1)/P2Y(12) receptors on adjacent PLTs;
      and (iv) the recursive amplification of PMP and PK release from these PLTs.

PMID- 18824537
TI  - An AraC-type transcriptional regulator encoded on the Enterococcus faecalis
      pathogenicity island contributes to pathogenesis and intracellular macrophage
      survival.
AB  - A gene encoding a putative AraC-type transcriptional regulator was identified on
      the 153-kb pathogenicity island (PAI) found among virulent Enterococcus faecalis
      strains. In an effort to understand the function of this regulator, designated
      PerA (for pathogenicity island-encoded regulator), we first examined the
      expression of the perA gene in the original PAI strain MMH594 and in an unrelated
      clinical isolate E99 by reverse transcription-PCR. Interestingly, expression
      analysis revealed no detectable perA transcript in MMH594, whereas a transcript
      was observed in strain E99. Nucleotide sequence analysis revealed that this
      altered expression between the two strains was attributable to the differential
      location of an IS1191 element within the putative promoter region upstream of the
      perA gene. In order to determine the role of this putative regulator in E.
      faecalis pathogenesis, a perA-deficient mutant was created in strain E99, and the
      wild-type and mutant pair were compared for phenotypic differences. In in vitro
      biofilm assays, the mutant strain showed a significantly higher level of growth
      medium-specific biofilm formation compared to the wild type. However, in a murine
      intraperitoneal infection model, the mutant strain was significantly less
      pathogenic. The mutant was also attenuated for survival within macrophages in
      vitro. These findings highlight the importance of PerA as a regulator of biofilm
      formation and survival within macrophages and is likely a regulator controlling
      determinants important to pathogenesis.

PMID- 18824538
TI  - A type IV secretion system contributes to intracellular survival and replication
      of Burkholderia cenocepacia.
AB  - Burkholderia cenocepacia is an important respiratory pathogen in persons with
      cystic fibrosis (CF). Recent studies indicate that B. cenocepacia survives within
      macrophages and airway epithelial cells in vitro by evading endosome-lysosome
      fusion. We investigated the role of a plasmid-encoded type IV secretion system in
      the intracellular survival, replication, and processing of B. cenocepacia. Both a
      wild-type strain (K56-2) and its type IV secretion system mutant (designated
      LC101) entered and replicated in CF airway epithelial cells and monocyte-derived
      macrophages. However, significantly more intracellular K56-2 than LC101 bacteria
      were found in both cell types at 24 h postinfection. Colocalization of bacteria
      with markers of the classical endocytic pathway indicated that although both K56
      2 and LC101 reside transiently in early endosomes, a greater proportion of the
      mutant bacteria are targeted to lysosomal degradation. In contrast, wild-type
      bacteria escape from the classical endocytic pathway and traffic to the
      endoplasmic reticulum, where they replicate. Our results show that the
      intracellular processing of B. cenocepacia is similar in both professional and
      nonprofessional phagocytes and that a functional plasmid-encoded type IV
      secretion system contributes to the survival and replication of B. cenocepacia in
      eukaryotic cells.

PMID- 18824539
TI  - Cytotoxic-T-lymphocyte-associated antigen 4 blockade abrogates protection by
      regulatory T cells in a mouse model of microbially induced innate immune-driven
      colitis.
AB  - Cytotoxic-T-lymphocyte-associated antigen 4 (CTLA-4) expressed at high levels by
      CD4(+) CD25(+) CD45RB(low) regulatory T cells (Treg) is essential to their
      homeostatic and immunoregulatory functions. However, its relevance to anti
      inflammatory roles of Treg in the context of colitogenic innate immune response
      during pathogenic bacterial infections has not been examined. We showed earlier
      in Rag2-deficient 129/SvEv mice that Treg cells are capable of suppressing
      colitis and colon cancer triggered by Helicobacter hepaticus, a widespread murine
      enterohepatic pathogen. Using this model, we now examined the effects of antibody
      blockade of CTLA-4 on Treg function during innate immune inflammatory response.
      Consistent with our previous findings, we found that a single adoptive transfer
      of Treg cells prior to infection prevented colitis development despite persistent
      H. hepaticus infection in recipient mice. However, when infected mice were
      injected with anti-CTLA-4 antibody along with Treg cell transfer, they developed
      a severe acute colitis with poor body condition that was not observed in Rag2(-/
      ) mice without Treg cell transfer. Despite high numbers of Foxp3(+) Treg cells,
      evident by immunohistochemical analyses in situ, the CTLA-4 antibody-treated mice
      had severely inflamed colonic mucosa and increased rather than decreased
      expression levels of cytokines gamma interferon and interleukin-2. These findings
      indicate that antibody blockade of CTLA-4 clearly abrogates Treg cell ability to
      suppress innate immune-driven colitis and suggest that Treg cell CTLA-4 cognate
      interactions may be necessary to maintain homeostasis among cells of innate
      immunity.

PMID- 18824540
TI  - Ras is required for the cyclic AMP-dependent activation of Rap1 via Epac2.
AB  - Exchange proteins activated by cAMP (cyclic AMP) 2 (Epac2) is a guanine
      nucleotide exchange factor for Rap1, a small G protein involved in many cellular
      functions, including cell adhesion, differentiation, and exocytosis. Epac2
      interacts with Ras-GTP via a Ras association (RA) domain. Previous studies have
      suggested that the RA domain was dispensable for Epac2 function. Here we show for
      the first time that Ras and cAMP regulate Epac2 function in a parallel fashion
      and the Ras-Epac2 interaction is required for the cAMP-dependent activation of
      endogenous Rap1 by Epac2. The mechanism for this requirement is not allosteric
      activation of Epac2 by Ras but the compartmentalization of Epac2 on the Ras
      containing membranes. A computational modeling is consistent with this
      compartmentalization being a function of both the level of Ras activation and the
      affinity between Ras and Epac2. In PC12 cells, a well-established model for
      sympathetic neurons, the Epac2 signaling is coupled to activation of mitogen
      activated protein kinases and contributes to neurite outgrowth. Taken together,
      the evidence shows that Epac2 is not only a cAMP sensor but also a bona fide Ras
      effector. Coincident detection of both cAMP and Ras signals is essential for
      Epac2 to activate Rap1 in a temporally and spatially controlled manner.

PMID- 18824541
TI  - Functional regulation of MyD88-activated interferon regulatory factor 5 by K63
      linked polyubiquitination.
AB  - Interferon regulatory factor 5 (IRF-5) plays an important role in the innate
      antiviral and inflammatory response. Specific IRF-5 haplotypes are associated
      with dysregulated expression of type I interferons and predisposition to
      autoimmune disorders. IRF-5 is activated by Toll-like receptor 7 (TLR7) and TLR9
      via the MyD88 pathway, where it interacts with both MyD88 and the E3 ubiquitin
      ligase, TRAF6. To understand the role of these interactions in the regulation of
      IRF-5, we examined the role of ubiquitination and showed that IRF-5 is subjected
      to TRAF6-mediated K63-linked ubiquitination, which is important for IRF-5 nuclear
      translocation and target gene regulation. We show that while the murine IRF-5 and
      human IRF-5 variant 4 (HuIRF-5v4) and HuIRF-5v5 are ubiquitinated, an IRF-5 bone
      marrow variant mutant containing an internal deletion of 288 nucleotides is not
      ubiquitinated. Lysine residues at positions 410 and 411 in a putative TRAF6
      consensus binding domain of IRF-5 are the targets of K63-linked ubiquitination.
      Mutagenesis of these two lysines abolished IRF-5 ubiquitination, nuclear
      translocation, and the IFNA promoter-inducing activity but not the IRF-5-TRAF6
      interaction. Finally, we show that IRAK1 associates with IRF-5 and that this
      interaction precedes and is required for IRF-5 ubiquitination and activation.
      Thus, our findings offer a new mechanistic insight into IRF-5 gene induction
      program through hitherto unknown processes of IRF-5 ubiquitination.

PMID- 18824542
TI  - Laforin negatively regulates cell cycle progression through glycogen synthase
      kinase 3beta-dependent mechanisms.
AB  - Glycogen synthase kinase 3beta (GSK-3beta) represses cell cycle progression by
      directly phosphorylating cyclin D1 and indirectly regulating cyclin D1
      transcription by inhibiting Wnt signaling. Recently, we reported that the Epm2a
      encoded laforin is a GSK-3beta phosphatase and a tumor suppressor. The cellular
      mechanism for its tumor suppression remains unknown. Using ex vivo thymocytes and
      primary embryonic fibroblasts from Epm2a(-/-) mice, we show here a general
      function of laforin in the cell cycle regulation and repression of cyclin D1
      expression. Moreover, targeted mutation of Epm2a increased the phosphorylation of
      Ser9 on GSK-3beta while having no effect on the phosphorylation of Ser21 on GSK
      3alpha. In the GSK-3beta(+/+) but not the GSK-3beta(-/-) cells, Epm2a small
      interfering RNA significantly enhanced cell growth. Consistent with an increased
      level of cyclin D1, the phosphorylation of retinoblastoma protein (Rb) and the
      levels of Rb-E2F-regulated genes cyclin A, cyclin E, MCM3, and PCNA are also
      elevated. Inhibitors of GSK-3beta selectively increased the cell growth of
      Epm2a(+/+) but not of Epm2a(-/-) cells. Taken together, our data demonstrate that
      laforin is a selective phosphatase for GSK-3beta and regulates cell cycle
      progression by GSK-3beta-dependent mechanisms. These data provide a cellular
      basis for the tumor suppression activity of laforin.

PMID- 18824543
TI  - Tumor hypoxia blocks Wnt processing and secretion through the induction of
      endoplasmic reticulum stress.
AB  - Poorly formed tumor blood vessels lead to regions of microenvironmental stress
      due to depletion of oxygen and glucose and accumulation of waste products
      (acidosis). These conditions contribute to tumor progression and correlate with
      poor patient prognosis. Here we show that the microenvironmental stresses found
      in the solid tumor are able to inhibit the canonical Wnt/beta-catenin signaling
      pathway. However, tumor cells harboring common beta-catenin pathway mutations,
      such as loss of adenomatous polyposis coli, are insensitive to this novel hypoxic
      effect. The underlying mechanism responsible is hypoxia-induced endoplasmic
      reticulum (ER) stress that inhibits normal Wnt protein processing and secretion.
      ER stress causes dissociation between GRP78/BiP and Wnt, an interaction essential
      for its correct posttranslational processing. Microenvironmental stress can
      therefore block autocrine and paracrine signaling of the Wnt/beta-catenin pathway
      and negatively affect tumor growth. This study provides a general paradigm
      relating oxygen status to ER function and growth factor signaling.

PMID- 18824544
TI  - NADPH oxidase-dependent generation of lysophosphatidylserine enhances clearance
      of activated and dying neutrophils via G2A.
AB  - Exofacial phosphatidylserine (PS) is an important ligand mediating apoptotic cell
      clearance by phagocytes. Oxidation of PS fatty acyl groups (oxPS) during
      apoptosis reportedly mediates recognition through scavenger receptors. Given the
      oxidative capacity of the neutrophil NADPH oxidase, we sought to identify oxPS
      signaling species in stimulated neutrophils. Using mass spectrometry analysis,
      only trace amounts of previously characterized oxPS species were found.
      Conversely, 18:1 and 18:0 lysophosphatidylserine (lyso-PS), known bioactive
      signaling phospholipids, were identified as abundant modified PS species
      following activation of the neutrophil oxidase. NADPH oxidase inhibitors blocked
      the production of lyso-PS in vitro, and accordingly, its generation in vivo by
      activated, murine neutrophils during zymosan-induced peritonitis was absent in
      mice lacking a functional NADPH oxidase (gp91phox-/-). Treatment of macrophages
      with lyso-PS enhanced the uptake of apoptotic cells in vitro, an effect that was
      dependent on signaling via the macrophage G2A receptor. Similarly, endogenously
      produced lyso-PS also enhanced the G2A-mediated uptake of activated PS-exposing
      (but non-apoptotic) neutrophils, raising the possibility of non-apoptotic
      mechanisms for removal of inflammatory cells during resolution. Finally, antibody
      blockade of G2A signaling in vivo prolonged zymosan-induced neutrophilia in wild
      type mice, whereas having no effect in gp91phox-/- mice where lyso-PS are not
      generated. Taken together, we show that lyso-PS are modified PS species generated
      following activation of the NADPH oxidase and lyso-PS signaling through the
      macrophage G2A functions to enhance existing receptor/ligand systems for optimal
      resolution of neutrophilic inflammation.

PMID- 18824545
TI  - Selective structural change by spermidine in the bulged-out region of double
      stranded RNA and its effect on RNA function.
AB  - Polyamines play important roles in cell growth mainly through their interaction
      with RNA. We have previously reported that polyamines stimulate the synthesis of
      oligopeptide-binding protein OppA in Escherichia coli and the formation of Ile
      tRNA in rat liver (Igarashi, K., and Kashiwagi, K. (2000) Biochem. Biophys. Res.
      Commun. 271, 559-564). These effects involve an interaction of polyamines with
      the bulged-out region of double-stranded RNA in the initiation region of OppA
      mRNA and in the acceptor stem of rat liver tRNA(Ile). In this study, the effects
      of polyamines on E. coli OppA synthesis and rat liver Ile-tRNA formation were
      compared using OppA mRNA and tRNA(Ile) with or without the bulged-out region of
      double-stranded RNA. The results indicate that the bulged-out region is involved
      in polyamine stimulation of OppA synthesis and Ile-tRNA formation. A selective
      structural change by spermidine in the bulged-out region of double-stranded RNA
      was confirmed by circular dichroism.

PMID- 18824546
TI  - Regulation of insulin granule turnover in pancreatic beta-cells by cleaved
      ICA512.
AB  - Insulin maintains homeostasis of glucose by promoting its uptake into cells from
      the blood. Hyperglycemia triggers secretion of insulin from pancreatic beta
      cells. This process is mediated by secretory granule exocytosis. However, how
      beta-cells keep granule stores relatively constant is still unknown. ICA512 is an
      intrinsic granule membrane protein, whose cytosolic domain binds beta2
      syntrophin, an F-actin-associated protein, and is cleaved upon granule
      exocytosis. The resulting cleaved cytosolic fragment, ICA512-CCF, reaches the
      nucleus and up-regulates the transcription of granule genes, including insulin
      and ICA512. Here, we show that ICA512-CCF also dimerizes with intact ICA512 on
      granules, thereby displacing it from beta2-syntrophin. This leads to increased
      granule mobility and insulin release. Based on these findings, we propose a model
      whereby the generation of ICA512-CCF first amplifies insulin secretion. The
      ensuing reduction of granule stores would then increase the probability of newly
      generated ICA512-CCF to reach the nucleus and enhance granule biogenesis, thus
      allowing beta-cells to constantly adjust production of granules to their storage
      size and consumption. Pharmacological modulation of these feedback loops may
      alleviate deficient insulin release in diabetes.

PMID- 18824548
TI  - Deciphering the ligand-binding sites in the Borrelia burgdorferi complement
      regulator-acquiring surface protein 2 required for interactions with the human
      immune regulators factor H and factor H-like protein 1.
AB  - Borrelia burgdorferi, the etiologic agent of Lyme disease, employs sophisticated
      means to evade killing by its mammalian hosts. One important immune escape
      mechanism is the inhibition of complement activation mediated by interactions of
      the host-derived immune regulators factor H (CFH) and factor H-like protein 1
      (CFHL1) with borrelial complement regulator-acquiring surface proteins
      (BbCRASPs). BbCRASP-2 is a distinctive CFH- and CFHL1-binding protein that is
      produced by serum-resistant B. burgdorferi strains. Here we show that binding of
      CFH by BbCRASP-2 is due to electrostatic as well as hydrophobic forces. In
      addition, 14 individual amino acid residues of BbCRASP-2 were identified as being
      involved in CFH and CFHL1 binding. Alanine substitutions of most of those
      residues significantly inhibited binding of CFH and/or CFHL1 by recombinant
      BbCRASP-2 proteins. To conclusively define the effects of BbCRASP-2 residue
      substitutions on serum sensitivity in the bacterial context, a serum-sensitive
      Borrelia garinii strain was transformed with plasmids that directed production of
      either wild-type or mutated BbCRASP-2 proteins. Critical amino acid residues
      within BbCRASP-2 were identified, with bacteria producing distinct mutant
      proteins being unable to bind either CFH or CFHL1, showing high levels of
      complement components C3, C6, and C5b-9 deposited on their surfaces and being
      highly sensitive to killing by normal serum. Collectively, we mapped a
      structurally sensitive CFH/CFHL1 binding site within borrelial BbCRASP-2 and
      identified single amino acid residues potentially involved in the interaction
      with both complement regulators.

PMID- 18824549
TI  - Acidic mammalian chitinase is secreted via an ADAM17/epidermal growth factor
      receptor-dependent pathway and stimulates chemokine production by pulmonary
      epithelial cells.
AB  - Acidic mammalian chitinase (AMCase) is expressed in an exaggerated fashion in
      epithelial cells at sites of pulmonary T helper cell type 2 inflammation and
      plays important roles in the pathogenesis of anti-parasite and asthma-like
      responses. However, the mechanisms that control epithelial cell AMCase secretion
      and its effector responses have not been adequately defined. To address these
      issues, we used in vivo and in vitro experimental systems to define the pathways
      of epithelial AMCase secretion and its epithelial regulatory effects. Here we
      demonstrate that, in murine T helper cell type 2 modeling systems, AMCase
      colocalizes with the epidermal growth factor receptor (EGFR) and ADAM17 (a
      membrane disintegrin and metallopeptidase 17) in lung epithelial cells. In vitro
      cotransfection experiments in A549 cells demonstrated that AMCase and EGFR
      physically interact with each other. Cotransfection of AMCase and EGFR also
      increased, whereas EGFR inhibition decreased AMCase secretion. Interestingly,
      AMCase secretion was not significantly altered by treatment with EGF but was
      significantly decreased when the upstream EGFR transactivator ADAM17 was
      inhibited. AMCase secretion was also decreased when the EGFR-downstream Ras was
      blocked. Transfected and recombinant AMCase induced epithelial cell production of
      CCL2, CCL17, and CXCL8. These studies demonstrate that lung epithelial cells
      secrete AMCase via an EGFR-dependent pathway that is activated by ADAM17 and
      mediates its effects via Ras. They also demonstrate that the AMCase that is
      secreted feeds back in an autocrine and/or paracrine fashion to stimulate
      pulmonary epithelial cell chemokine production.

PMID- 18824550
TI  - Mycobacterium avium glycopeptidolipids require specific acetylation and
      methylation patterns for signaling through toll-like receptor 2.
AB  - Toll-like receptors (TLRs) recognize pathogen-associated molecules and play a
      vital role in promoting an immune response against invading microbes. TLR2, one
      of the key members of the TLR family, recognizes a wide variety of microbial
      products, including lipoproteins and lipopeptides, from a number of pathogens.
      Recent studies from our laboratory indicate that glycopeptidolipids (GPLs), a
      major surface component of Mycobacterium avium and other non-tuberculosis
      mycobacteria, are ligands for TLR2. However, the molecular requirements necessary
      for the GPL-TLR2 interaction were not defined in this report. In the present
      study we isolated different GPL species from M. avium, and using mass
      spectrometry and NMR analyses, characterized the molecular requirements of the
      GPL-TLR2 interaction. Interestingly, the extent of the respective acetylation and
      methylation of the 6-deoxytalose and rhamnose contained within the core GPL
      structure dictated whether the GPL signaled through TLR2. These experiments
      illustrate how subtle changes in a complex TLR2 ligand can alter its affinity for
      this important receptor, and suggest that M. avium could potentially modify its
      GPL structure to limit its interaction with TLR2.

PMID- 18824551
TI  - Dual specificity A-kinase anchoring proteins (AKAPs) contain an additional
      binding region that enhances targeting of protein kinase A type I.
AB  - A-kinase anchoring proteins (AKAPs) target protein kinase A (PKA) to a variety of
      subcellular locations. Conventional AKAPs contain a 14-18-amino acid sequence
      that forms an amphipathic helix that binds with high affinity to the regulatory
      (R) subunit of PKA type II. More recently, a group of dual specificity AKAPs has
      been classified on the basis of their ability to bind the PKA type I and the PKA
      type II isozymes. In this study we show that dual specificity AKAPs contain an
      additional PKA binding determinant called the RI Specifier Region (RISR). A
      variety of protein interaction assays and immunoprecipitation and
      immunolocalization experiments indicates that the RISR augments RI binding in
      vitro and inside cells. Cellular delivery of the RISR peptide uncouples RI
      anchoring to Ezrin leading to release of T cell inhibition by cAMP. Likewise,
      expression of mutant Ezrin forms where RI binding has been abrogated by
      substitution of the RISR sequence prevents cAMP-mediated inhibition of T cell
      function. Thus, we propose that the RISR acts in synergy with the amphipathic
      helix in dual specificity anchoring proteins to enhance anchoring of PKA type I.

PMID- 18824552
TI  - Gene-specific requirement of a nuclear protein, IkappaB-zeta, for promoter
      association of inflammatory transcription regulators.
AB  - Expression of many inflammatory genes is induced through activation of the
      transcription factor NF-kappaB. In contrast to the advanced understanding of
      cytoplasmic control of NF-kappaB activation, its regulation in the nucleus has
      not been fully understood despite its importance in selective gene expression. We
      previously identified an inducible nuclear protein, IkappaB-zeta, and
      demonstrated that this molecule is indispensable for the expression of a group of
      NF-kappaB-regulated genes. In this study, we established a unique gene induction
      system, in which IkappaB-zeta is expressed independently of inflammatory stimuli,
      to specifically investigate the molecular basis underlying IkappaB-zeta-mediated
      gene activation. We show that in the presence of IkappaB-zeta other primary
      response genes are dispensable for the expression of the target secondary
      response genes. ChIP analyses revealed that IkappaB-zeta is required for stimulus
      induced recruitment of NF-kappaB onto the target promoter in a gene-specific
      manner. Surprisingly, IkappaB-zeta is also necessary for the gene-selective
      promoter recruitment of another inflammatory transcription factor, C/EBPbeta, and
      the chromatin remodeling factor Brg1. We propose a new gene regulatory mechanism
      underlying the selective expression of inflammatory genes.

PMID- 18824553
TI  - Costs and cost-effectiveness of different follow-up schedules for detection of
      occupational hepatitis C virus infection.
AB  - OBJECTIVE: The purpose of this study was to compare the costs and cost
      effectiveness (C/E) of early hepatitis C virus (HCV) RNA testing (alternative-US
      recommendations) after occupational exposure to HCV with existing follow-up
      strategies: (1) French, anti-HCV antibodies and alanine transaminase (ALT)
      activity at months 1, 3 and 6; (2) European, monthly ALT activity for 4 months
      and anti-HCV antibodies at month 6; (3) and baseline-US, anti-HCV antibodies and
      ALT activity at month 6. METHODS: A decision tree simulated each strategy for
      7300 healthcare workers (HCWs) exposed to HCV each year in France, taking into
      account the impact of early diagnosis on the response to antiviral treatment and
      the deterioration of HCW quality of life after exposure. RESULTS: For a HCV
      transmission risk of 0.5% after exposure, the French strategy led to the highest
      costs/person (181.40 euros) and the baseline-US strategy to the lowest (126.60
      euros) (178.50 euros) for alternative-US). The shortest mean time to HCV
      infection diagnosis (1 month) and the lowest number of chronic hepatitis C (CHC)
      patients (1.9/7300 HCWs exposed) was obtained with the alternative-US strategy
      (vs 6 months and 7.9 CHC, respectively with baseline-US). Compared with the
      alternative-US, the French strategy was associated with higher costs and lower
      utilities, and the European with a higher incremental C/E ratio. Compared with
      the baseline-US strategy, the alternative-US strategy C/E ratio was 2020 euros
      per quality-adjusted life year saved. CONCLUSION: In HCWs exposed to HCV, a
      strategy based on early HCV RNA testing shortens the period during which the
      HCW's wait for his HCV status, leads to lower risk of progression to CHC and is
      reasonably cost-effective.

PMID- 18824554
TI  - Melanin-concentrating hormone (MCH) modulates C difficile toxin A-mediated
      enteritis in mice.
AB  - OBJECTIVE: Melanin-concentrating hormone (MCH) is a hypothalamic orexigenic
      neuropeptide that regulates energy balance. However, the distribution of MCH and
      its receptor MCHR1 in tissues other than brain suggested additional, as yet
      unappreciated, roles for this neuropeptide. Based on previous paradigms and the
      presence of MCH in the intestine as well as in immune cells, its potential role
      in gut innate immune responses was examined. METHODS: In human intestinal
      xenografts grown in mice, changes in the expression of MCH and its receptors
      following treatment with Clostridium difficile toxin A, the causative agent of
      antibiotic-associated diarrhoea in hospitalised patients, were examined. In
      colonocytes, the effect of C difficile toxin A treatment on MCHR1 expression, and
      of MCH on interleukin 8 (IL8) expression was examined. MCH-deficient mice and
      immunoneutralisation approaches were used to examine the role of MCH in the
      pathogenesis of C difficile toxin A-mediated acute enteritis. RESULTS:
      Upregulation of MCH and MCHR1 expression was found in the human intestinal
      xenograft model, and of MCHR1 in colonocytes following exposure to toxin A.
      Treatment of colonocytes with MCH resulted in IL8 transcriptional upregulation,
      implying a link between MCH and inflammatory pathways. In further support of this
      view, MCH-deficient mice developed attenuated toxin A-mediated intestinal
      inflammation and secretion, as did wild-type mice treated with an antibody
      against MCH or MCHR1. CONCLUSION: These findings signify MCH as a mediator of C
      difficile-associated enteritis and possibly of additional gut pathogens. MCH may
      mediate its proinflammatory effects at least in part by acting on epithelial
      cells in the intestine.

PMID- 18824555
TI  - Molecular prediction of disease risk and severity in a large Dutch Crohn's
      disease cohort.
AB  - BACKGROUND: Crohn's disease and ulcerative colitis have a complex genetic
      background. We assessed the risk for both the development and severity of the
      disease by combining information from genetic variants associated with
      inflammatory bowel disease (IBD). METHODS: We studied 2804 patients (1684 with
      Crohn's disease and 1120 with ulcerative colitis) and 1350 controls from seven
      university hospitals. Details of the phenotype were available for 1600 patients
      with Crohn's disease and for 800 with ulcerative colitis. Genetic association for
      disease susceptibility was tested for the nucleotide-binding and oligomerisation
      domain 2 gene (NOD2), the IBD5 locus, the Drosophila discs large homologue 5 and
      autophagy-related 16-like 1 genes (DLG5 and ATG16L1) and the interleukin 23
      receptor gene (IL23R). Interaction analysis was performed for Crohn's disease
      using the most associated single nucleotide polymorphism (SNP) for each locus.
      Odds ratios were calculated in an ordinal regression analysis with the number of
      risk alleles as an independent variable to analyse disease development and
      severity. RESULTS: Association with Crohn's disease was confirmed for NOD2, IBD5,
      DLG5, ATG16L1 and IL23R. Patients with Crohn's disease carry more risk alleles
      than controls (p = 3.85 x 10(-22)). Individuals carrying an increasing number of
      risk alleles have an increasing risk for Crohn's disease, consistent with an
      independent effects multiplicative model (trend analysis p = 4.25 x 10(-23)).
      Patients with Crohn's disease with a more severe disease course, operations or an
      age of onset below 40 years have more risk alleles compared to non-stricturing,
      non-penetrating behaviour (p = 0.0008), no operations (p = 0.02) or age of onset
      above 40 years (p = 0.028). CONCLUSION: Crohn's disease is a multigenic disorder.
      An increase in the number of risk alleles is associated with an increased risk
      for the development of Crohn's disease and with a more severe disease course.
      Combining information from the known common risk polymorphisms may enable
      clinicians to predict the course of Crohn's disease.

PMID- 18824556
TI  - Impaired intestinal barrier integrity in the colon of patients with irritable
      bowel syndrome: involvement of soluble mediators.
AB  - BACKGROUND: Growing evidence suggests that patients with irritable bowel syndrome
      (IBS) have increased intestinal permeability. In addition, mucosal soluble
      mediators are involved in the pathophysiology of pain in IBS. We aimed to
      investigate (1) paracellular permeability in colonic biopsies of patients with
      IBS; and (2) the ability of soluble factors from colonic biopsies to reproduce
      these alterations in vitro. METHODS: Paracellular permeability in colonic
      biopsies of healthy subjects and patients with IBS was measured by mounting the
      biopsies in Ussing chambers. Cleared supernatant (SUP) of the culture from
      colonic biopsies was collected and applied to Caco-2 cells for 48 h. Paracellular
      permeability and transepithelial resistance (TER) were evaluated. mRNA expression
      of the tight junction proteins, zonula occludens (ZO)-1 and occludin, was
      assessed in colonic biopsies. Abdominal pain was assessed using a validated
      questionnaire. RESULTS: Permeability of colonic biopsies was significantly higher
      in patients with IBS compared to healthy subjects. These changes were associated
      with significantly lower expression of ZO-1 mRNA in biopsies of IBS as compared
      to healthy subjects. Compared to healthy subjects, SUP of IBS markedly reduced
      TER and significantly increased permeability in Caco-2 cells. SUP of IBS patients
      induced a significant decrease of ZO-1 mRNA in Caco-2 as compared to healthy
      subjects. SUP-induced increased paracellular permeability correlated with the
      severity of abdominal pain. CONCLUSIONS: Our study shows that colonic soluble
      mediators are able to reproduce functional (permeability) and molecular (ZO-1
      mRNA expression) alterations observed in IBS patients. These findings might pave
      the way both to identify novel biomarkers as well as new therapeutic targets in
      IBS.

PMID- 18824557
TI  - Prospective evaluation of mitotane toxicity in adrenocortical cancer patients
      treated adjuvantly.
AB  - Toxicity of adjuvant mitotane treatment is poorly known; thus, our aim was to
      assess prospectively the unwanted effects of adjuvant mitotane treatment and
      correlate the findings with mitotane concentrations. Seventeen consecutive
      patients who were treated with mitotane after radical resection of adrenocortical
      cancer (ACC) from 1999 to 2005 underwent physical examination, routine laboratory
      evaluation, monitoring of mitotane concentrations, and a hormonal work-up at
      baseline and every 3 months till ACC relapse or study end (December 2007).
      Mitotane toxicity was graded using NCI CTCAE criteria. All biochemical
      measurements were performed at our center and plasma mitotane was measured by an
      in-house HPLC assay. All the patients reached mitotane concentrations >14 mg/l
      and none of them discontinued definitively mitotane for toxicity; 14 patients
      maintained consistently elevated mitotane concentrations despite tapering of the
      drug. Side effects occurred in all patients but were manageable with palliative
      treatment and adjustment of hormone replacement therapy. Mitotane affected
      adrenal steroidogenesis with a more remarkable inhibition of cortisol and DHEAS
      than aldosterone. Mitotane induced either perturbation of thyroid function
      mimicking central hypothyroidism or, in male patients, inhibition of testosterone
      secretion. The discrepancy between salivary and serum cortisol, as well as
      between total and free testosterone, is due to the mitotane-induced increase in
      hormone-binding proteins which complicates interpretation of hormone
      measurements. A low-dose monitored regimen of mitotane is tolerable and able to
      maintain elevated drug concentrations in the long term. Mitotane exerts a complex
      effect on the endocrine system that may require multiple hormone replacement
      therapy.

PMID- 18824558
TI  - Metastases but not cardiovascular mortality reduces life expectancy following
      surgical resection of apparently benign pheochromocytoma.
AB  - The treatment of choice for non-metastatic pheochromocytoma is surgical
      resection. Its goals are to abolish catecholamine hypersecretion, normalize blood
      pressure, and prevent further tumor growth or progression to metastatic disease.
      Data on long-term mortality and morbidity after pheochromocytoma surgery are
      limited. We here report a retrospective study on the long-term outcome after
      surgery for apparently benign pheochromocytoma at the Radboud University Nijmegen
      Medical Centre. Data on clinical presentation, treatment, post-surgical blood
      pressure and recurrence, metastasis and death were collected of 69 consecutive
      patients (January 1966-December 2000; follow-up: until death or January 2006).
      Survival was compared with survival of a matched reference population. Two
      patients died of surgical complications. All ten patients with metastatic disease
      (including three diagnosed at first surgery) died. At follow-up, 40 patients were
      alive and recurrence free and three patients were lost to follow up. Two patients
      experienced a benign recurrence. Mean+/-s.d. follow-up was 10.2+/-7.5 (median 9,
      range 1-38) years. Kaplan-Meier estimates for 5- and 10-year survival since
      surgery were 85.8% (95% CI: 77.2-94.4%) and 74.2% (95% CI: 62.0-86.4%) for
      patients versus 95.5 and 89.4% in the reference population (P<0.05). Sixty-four
      percent of all patients with hypertension prior to surgery showed a significant
      decrease in blood pressure, but remained hypertensive after surgery. In
      conclusion, compared with the general population patients have a reduced life
      expectancy following pheochromocytoma surgery, due to their risk of developing
      metastatic disease. Only one-third becomes normotensive without antihypertensive
      medication. Therefore, lifelong follow-up is warranted.

PMID- 18824559
TI  - ERBB2 influences the subcellular localization of the estrogen receptor in
      tamoxifen-resistant MCF-7 cells leading to the activation of AKT and RPS6KA2.
AB  - Acquired resistance to endocrine therapies remains a major clinical obstacle in
      hormone-sensitive breast tumors. We used an MCF-7 breast tumor cell line (Tam(R)
      1) resistant to tamoxifen to investigate this mechanism. We demonstrate that
      Tam(R)-1 express elevated levels of phosphorylated AKT and MAPK3/1-activated
      RPS6KA2 compared with the parental MCF-7 cell line (MCF-7). There was no change
      in the level of total ESR between the two cell lines; however, the Tam(R)-1 cells
      had increased phosphorylation of ESR1 ser(167). SiRNA blockade of AKT or MAPK3/1
      had little effect on ESR1 ser(167) phosphorylation, but a combination of the two
      siRNAs abrogated this. Co-localization studies revealed an association between
      ERBB2 and ESR1 in the Tam(R)-1 but not MCF-7 cells. ESR1 was redistributed to
      extranuclear sites in Tam(R)-1 and was less transcriptionally competent compared
      with MCF-7 suggesting that nuclear ESR1 activity was suppressed in Tam(R)-1.
      Tamoxifen resistance in the Tam(R)-1 cells could be partially overcome by the
      ERBB2 inhibitor AG825 in combination with tamoxifen, and this was associated with
      re-localization of ESR1 to the nucleus. These data demonstrate that tamoxifen
      resistant cells have the ability to switch between ERBB2 or ESR1 pathways
      promoting cell growth and that pharmacological inhibition of ERBB2 may be a
      therapeutic strategy for overcoming tamoxifen resistance.

PMID- 18824560
TI  - Minimum substrate requirements of endoglycosidase activities toward dermatan
      sulfate by electrospray ionization-tandem mass spectrometry.
AB  - The catabolism of dermatan sulfate (DS) commences with endohydrolysis of the
      polysaccharide to oligosaccharides by proposed endo-beta-N-acetylhexosaminidase
      and endohexuronidase activities. To investigate the substrate specificities of
      these activities, we developed an assay to measure specific products of their
      action upon oligosaccharide substrates. Tetra- to tetradecasaccharides, rich in
      glucuronic acid (GlcA) or iduronic acid (IdoA), were obtained from chondroitinase
      ABC digests of chondroitin sulfate (CS)-A and DS, respectively, separated by gel
      filtration chromatography and characterized by electrospray ionization-tandem
      mass spectrometry (ESI-MS/MS). Endo-beta-N-acetylhexosaminidase and
      endohexuronidase cleavage of these oligosaccharides was then assessed by
      incubating with cell homogenate (source of endoglycosidase activity) and
      measuring di- to octasaccharide products derived from the nonreducing end of the
      substrate by ESI-MS/MS. We found that both activities preferentially degraded the
      GlcA-rich substrate, with minor activity toward the IdoA-rich substrate and that
      a minimum of four and five monosaccharides were required on the reducing side of
      the target glycosidic linkage for endo-beta-N-acetylhexosaminidase and
      endohexuronidase cleavage, respectively. Thus, the minimum-sized substrates were
      a hexasaccharide for endo-beta-N-acetylhexosaminidase and an octasaccharide for
      endohexuronidase. We observed that endo-beta-N-acetylhexosaminidase sequentially
      removed tetrasaccharides from the nonreducing end of oligosaccharides when
      unrestricted by substrate length, whereas endohexuronidase activity was random
      and comparatively low. The activities displayed acidic pH optima and were shown
      by subcellular fractionation to reside in lysosomes and late endosomes. We
      suggest that these activities represent the known Hyal-1 and endo-beta
      glucuronidase enzymes and that these enzymes act in concert to degrade GlcA-rich
      domains of DS but are less active toward regions containing IdoA.

PMID- 18824561
TI  - Glycobiology on the fly: developmental and mechanistic insights from Drosophila.
AB  - Drosophila melanogaster offers many unique advantages for deciphering the
      complexities of glycan biosynthesis and function. The completion of the
      Drosophila genome sequencing project as well as the comprehensive catalogue of
      existing mutations and phenotypes have lead to a prolific database where many of
      the genes involved in glycan synthesis, assembly, modification, and recognition
      have been identified and characterized. Recent biochemical and molecular studies
      have elucidated the structure of the glycans present in Drosophila. Powerful
      genetic approaches have uncovered a number of critical biological roles for
      glycans during development that impact on our understanding of their function
      during mammalian development. Here, we summarize key recent findings and provide
      evidence for the usefulness of this model organism in unraveling the complexities
      of glycobiology across many species.

PMID- 18824562
TI  - Identification of the Drosophila core 1 beta1,3-galactosyltransferase gene that
      synthesizes T antigen in the embryonic central nervous system and hemocytes.
AB  - T antigen (Galbeta1-3GalNAcalpha1-Ser/Thr), the well-known tumor-associated
      antigen, is a core 1 mucin-type O-glycan structure that is synthesized by core 1
      beta1,3-galactosyltransferase (C1beta3GalT), which transfers Gal from UDP-Gal to
      Tn antigen (GalNAcalpha1-Ser/Thr). Three putative C1beta3GalTs have been
      identified in Drosophila. However, although all three are expressed in embryos,
      their roles during embryogenesis have not yet been clarified. In this study, we
      used P-element inserted mutants to show that CG9520, one of the three putative
      C1beta3GalTs, synthesizes T antigen expressed on the central nervous system (CNS)
      during embryogenesis. We also found that T antigen was expressed on a subset of
      the embryonic hemocytes. CG9520 mutant embryos showed the loss of T antigens on
      the CNS and on a subset of hemocytes. Then, the loss of T antigens was rescued by
      precise excision of the P-element inserted into the CG9520 gene. Our data
      demonstrate that T antigens expressed on the CNS and on a subset of hemocytes are
      synthesized by CG9520 in the Drosophila embryo. In addition, we found that the
      number of circulating hemocytes was reduced in third instar larvae of CG9520
      mutant. We, therefore, named the CG9520 gene Drosophila core 1 beta1,3
      galactosyltransferase 1 because it is responsible for the synthesis and function
      of T antigen in vivo.

PMID- 18824563
TI  - The spindle assembly checkpoint is satisfied in the absence of interkinetochore
      tension during mitosis with unreplicated genomes.
AB  - The accuracy of chromosome segregation is enhanced by the spindle assembly
      checkpoint (SAC). The SAC is thought to monitor two distinct events: attachment
      of kinetochores to microtubules and the stretch of the centromere between the
      sister kinetochores that arises only when the chromosome becomes properly
      bioriented. We examined human cells undergoing mitosis with unreplicated genomes
      (MUG). Kinetochores in these cells are not paired, which implies that the
      centromere cannot be stretched; however, cells progress through mitosis. A SAC is
      present during MUG as cells arrest in response to nocodazole, taxol, or monastrol
      treatments. Mad2 is recruited to unattached MUG kinetochores and released upon
      their attachment. In contrast, BubR1 remains on attached kinetochores and
      exhibits a level of phosphorylation consistent with the inability of MUG spindles
      to establish normal levels of centromere tension. Thus, kinetochore attachment to
      microtubules is sufficient to satisfy the SAC even in the absence of
      interkinetochore tension.

PMID- 18824564
TI  - Grapes(Chk1) prevents nuclear CDK1 activation by delaying cyclin B nuclear
      accumulation.
AB  - Entry into mitosis is characterized by a dramatic remodeling of nuclear and
      cytoplasmic compartments. These changes are driven by cyclin-dependent kinase 1
      (CDK1) activity, yet how cytoplasmic and nuclear CDK1 activities are coordinated
      is unclear. We injected cyclin B (CycB) into Drosophila melanogaster embryos
      during interphase of syncytial cycles and monitored effects on cytoplasmic and
      nuclear mitotic events. In untreated embryos or embryos arrested in interphase
      with a protein synthesis inhibitor, injection of CycB accelerates nuclear
      envelope breakdown and mitotic remodeling of the cytoskeleton. Upon activation of
      the Grapes(checkpoint kinase 1) (Grp(Chk1))-dependent S-phase checkpoint,
      increased levels of CycB drives cytoplasmic but not nuclear mitotic events.
      Grp(Chk1) prevents nuclear CDK1 activation by delaying CycB nuclear accumulation
      through Wee1-dependent and independent mechanisms.

PMID- 18824565
TI  - The role of GTP binding and hydrolysis at the atToc159 preprotein receptor during
      protein import into chloroplasts.
AB  - The majority of nucleus-encoded chloroplast proteins are targeted to the
      organelle by direct binding to two membrane-bound GTPase receptors, Toc34 and
      Toc159. The GTPase activities of the receptors are implicated in two key import
      activities, preprotein binding and driving membrane translocation, but their
      precise functions have not been defined. We use a combination of in vivo and in
      vitro approaches to study the role of the Toc159 receptor in the import reaction.
      We show that atToc159-A864R, a receptor with reduced GTPase activity, can fully
      complement a lethal insertion mutation in the ATTOC159 gene. Surprisingly, the
      atToc159-A864R receptor increases the rate of protein import relative to wild
      type receptor in isolated chloroplasts by stabilizing the formation of a GTP
      dependent preprotein binding intermediate. These data favor a model in which the
      atToc159 receptor acts as part of a GTP-regulated switch for preprotein
      recognition at the TOC translocon.

PMID- 18824566
TI  - AP-2 factors act in concert with Notch to orchestrate terminal differentiation in
      skin epidermis.
AB  - The mechanisms by which mammalian epidermal stem cells cease to proliferate and
      embark upon terminal differentiation are still poorly understood. By
      conditionally ablating two highly expressed transcription factors, AP-2alpha and
      AP-2gamma, we unmasked functional redundancies and discovered an essential role
      for AP-2s in the process. In vivo and in vitro, AP-2 deficiency is accompanied by
      surprisingly minimal changes in basal gene expression but severely perturbed
      terminal differentiation and suppression of additional transcription factors and
      structural genes involved. In dissecting the underlying molecular pathways, we
      uncover parallel pathways involving AP-2 and Notch signaling, which converge to
      govern CCAAT/enhancer binding protein genes and orchestrate the transition from
      basal proliferation to suprabasal differentiation. Finally, we extend the
      striking similarities in compromising either Notch signaling or AP-2alpha/AP
      2gamma in developing skin to that in postnatal skin, where all hair follicles and
      sebaceous gland differentiation are also repressed and overt signs of
      premalignant conversion emerge.

PMID- 18824567
TI  - Notch1 signaling stimulates proliferation of immature cardiomyocytes.
AB  - The identification of the molecular mechanisms controlling cardiomyocyte
      proliferation during the embryonic, fetal, and early neonatal life appears of
      paramount interest in regard to exploiting this information to promote cardiac
      regeneration. Here, we show that the proliferative potential of neonatal rat
      cardiomyocytes is powerfully stimulated by the sustained activation of the Notch
      pathway. We found that Notch1 is expressed in proliferating ventricular immature
      cardiac myocytes (ICMs) both in vitro and in vivo, and that the number of Notch1
      positive cells in the heart declines with age. Notch1 expression in ICMs
      paralleled the expression of its Jagged1 ligand on non-myocyte supporting cells.
      The inhibition of Notch signaling in ICMs blocked their proliferation and induced
      apoptosis; in contrast, its activation by Jagged1 or by the constitutive
      expression of its activated form using an adeno-associated virus markedly
      stimulated proliferative signaling and promoted ICM expansion. Maintenance or
      reactivation of Notch signaling in cardiac myocytes might represent an
      interesting target for innovative regenerative therapy.

PMID- 18824568
TI  - Autonomy and robustness of translocation through the nuclear pore complex: a
      single-molecule study.
AB  - All molecular traffic between nucleus and cytoplasm occurs via the nuclear pore
      complex (NPC) within the nuclear envelope. In this study we analyzed the
      interactions of the nuclear transport receptors kapalpha2, kapbeta1,
      kapbeta1DeltaN44, and kapbeta2, and the model transport substrate, BSA-NLS, with
      NPCs to determine binding sites and kinetics using single-molecule microscopy in
      living cells. Recombinant transport receptors and BSA-NLS were fluorescently
      labeled by AlexaFluor 488, and microinjected into the cytoplasm of living HeLa
      cells expressing POM121-GFP as a nuclear pore marker. After bleaching the
      dominant GFP fluorescence the interactions of the microinjected molecules could
      be studied using video microscopy with a time resolution of 5 ms, achieving a
      colocalization precision of 30 nm. These measurements allowed defining the
      interaction sites with the NPCs with an unprecedented precision, and the
      comparison of the interaction kinetics with previous in vitro measurements
      revealed new insights into the translocation mechanism.

PMID- 18824569
TI  - Tre1 GPCR initiates germ cell transepithelial migration by regulating Drosophila
      melanogaster E-cadherin.
AB  - Despite significant progress in identifying the guidance pathways that control
      cell migration, how a cell starts to move within an intact organism, acquires
      motility, and loses contact with its neighbors is poorly understood. We show that
      activation of the G protein-coupled receptor (GPCR) trapped in endoderm 1 (Tre1)
      directs the redistribution of the G protein Gbeta as well as adherens junction
      proteins and Rho guanosine triphosphatase from the cell periphery to the lagging
      tail of germ cells at the onset of Drosophila melanogaster germ cell migration.
      Subsequently, Tre1 activity triggers germ cell dispersal and orients them toward
      the midgut for directed transepithelial migration. A transition toward invasive
      migration is also a prerequisite for metastasis formation, which often correlates
      with down-regulation of adhesion proteins. We show that uniform down-regulation
      of E-cadherin causes germ cell dispersal but is not sufficient for
      transepithelial migration in the absence of Tre1. Our findings therefore suggest
      a new mechanism for GPCR function that links cell polarity, modulation of cell
      adhesion, and invasion.

PMID- 18824570
TI  - Cerebrospinal fluid biomarkers in the evaluation of Alzheimer disease.

PMID- 18824571
TI  - Rapid and effective screening for lysosomal storage disease: how close are we?

PMID- 18824572
TI  - Requesting and interpreting urine albumin measurements in the primary health care
      setting.

PMID- 18824573
TI  - Multiple thiopurine S-methyltransferase variation detection: a step toward
      personalized medicine.

PMID- 18824574
TI  - A girl with severe hand swelling and abdominal cramps.

PMID- 18824577
TI  - Calibration of fractionated metanephrines in urine: still an issue?

PMID- 18824578
TI  - Maple syrup urine disease: newborn screening fails to discriminate between
      classic and variant forms.

PMID- 18824579
TI  - Association of the FABP2 T54 variant with plasma triglycerides and insulin
      resistance in a multiethnic population.

PMID- 18824580
TI  - Quantification of urinary light chains.

PMID- 18824581
TI  - Precision of high-throughput single-nucleotide polymorphism genotyping with
      fingernail DNA: comparison with blood DNA.

PMID- 18824582
TI  - The Death Receptor 3-TNF-like protein 1A pathway drives adverse bone pathology in
      inflammatory arthritis.
AB  - Rheumatoid arthritis (RA) is a chronic inflammatory disease of synovial joints
      that is associated with cartilage and bone destruction. Death Receptor 3 (DR3), a
      tumor necrosis factor (TNF) receptor superfamily member, has recently been
      associated with the pathogenesis of RA. We demonstrate that absence of DR3
      confers resistance to the development of adverse bone pathology in experimental
      antigen-induced arthritis (AIA). DR3(ko) mice exhibited a reduction in all
      histopathological hallmarks of AIA but, in particular, failed to develop
      subchondral bone erosions and were completely protected from this characteristic
      of AIA. In contrast, TNF-like protein 1A (TL1A), the ligand for DR3, exacerbated
      disease in a dose- and DR3-dependent fashion. Analysis of osteoclast number
      within AIA joint revealed a reduction in areas susceptible to bone erosion in
      DR3(ko) mice, whereas in vitro osteoclastogenesis assays showed that TL1A could
      directly promote osteoclastogenesis in mouse and man. Treatment with antagonistic
      anti-TL1A mAb protected animals in a systemic model of RA disease collagen
      induced arthritis. We therefore conclude that the DR3-TL1A pathway regulates
      joint destruction in two murine models of arthritis and represents a potential
      novel target for therapeutic intervention in inflammatory joint disease.

PMID- 18824583
TI  - Delta-like 4 is indispensable in thymic environment specific for T cell
      development.
AB  - The thymic microenvironment is required for T cell development in vivo. However,
      in vitro studies have shown that when hematopoietic progenitors acquire Notch
      signaling via Delta-like (Dll)1 or Dll4, they differentiate into the T cell
      lineage in the absence of a thymic microenvironment. It is not clear, however,
      whether the thymus supports T cell development specifically by providing Notch
      signaling. To address this issue, we generated mice with a loxP-flanked allele of
      Dll4 and induced gene deletion specifically in thymic epithelial cells (TECs). In
      the thymus of mutant mice, the expression of Dll4 was abrogated on the
      epithelium, and the proportion of hematopoietic cells bearing the intracellular
      fragment of Notch1 (ICN1) was markedly decreased. Corresponding to this, CD4 CD8
      double-positive or single-positive T cells were not detected in the thymus.
      Further analysis showed that the double-negative cell fraction was lacking T cell
      progenitors. The enforced expression of ICN1 in hematopoietic progenitors
      restored thymic T cell differentiation, even when the TECs were deficient in
      Dll4. These results indicate that the thymus-specific environment for determining
      T cell fate indispensably requires Dll4 expression to induce Notch signaling in
      the thymic immigrant cells.

PMID- 18824584
TI  - Human PMS2 deficiency is associated with impaired immunoglobulin class switch
      recombination.
AB  - Immunoglobulin (Ig) class switch recombination (CSR) deficiencies are rare
      primary immunodeficiencies characterized by the lack of switched isotype
      (IgG/IgA/IgE) production. In some cases, CSR deficiencies can be associated with
      abnormal somatic hypermutation. Analysis of CSR deficiencies has helped reveal
      the key functions of CSR-triggering molecules, i.e., CD40L, CD40, and effector
      molecules such as activation-induced cytidine deaminase and uracil N-glycosylase.
      We report a new form of B cell-intrinsic CSR deficiency found in three patients
      with deleterious, homozygous mutations in the gene encoding the PMS2 component of
      the mismatch repair machinery. CSR was found partially defective in vivo and
      markedly impaired in vitro. It is characterized by the defective occurrence of
      double-strand DNA breaks (DSBs) in switch regions and abnormal formation of
      switch junctions. This observation strongly suggests a role for PMS2 in CSR
      induced DSB generation.

PMID- 18824585
TI  - Delta-like 4 is the essential, nonredundant ligand for Notch1 during thymic T
      cell lineage commitment.
AB  - Thymic T cell lineage commitment is dependent on Notch1 (N1) receptor-mediated
      signaling. Although the physiological ligands that interact with N1 expressed on
      thymic precursors are currently unknown, in vitro culture systems point to Delta
      like 1 (DL1) and DL4 as prime candidates. Using DL1- and DL4-lacZ reporter knock
      in mice and novel monoclonal antibodies to DL1 and DL4, we show that DL4 is
      expressed on thymic epithelial cells (TECs), whereas DL1 is not detected. The
      function of DL4 was further explored in vivo by generating mice in which DL4
      could be specifically inactivated in TECs or in hematopoietic progenitors.
      Although loss of DL4 in hematopoietic progenitors did not perturb thymus
      development, inactivation of DL4 in TECs led to a complete block in T cell
      development coupled with the ectopic appearance of immature B cells in the
      thymus. These immature B cells were phenotypically indistinguishable from those
      developing in the thymus of conditional N1 mutant mice. Collectively, our results
      demonstrate that DL4 is the essential and nonredundant N1 ligand responsible for
      T cell lineage commitment. Moreover, they strongly suggest that N1-expressing
      thymic progenitors interact with DL4-expressing TECs to suppress B lineage
      potential and to induce the first steps of intrathymic T cell development.

PMID- 18824587
TI  - Sabine Ehrt: searching for mycobacterial stress points. Interview by Hema
      Bashyam.

PMID- 18824586
TI  - Mind bomb 1 in the lymphopoietic niches is essential for T and marginal zone B
      cell development.
AB  - Notch signaling regulates lineage decisions at multiple stages of lymphocyte
      development, and Notch activation requires the endocytosis of Notch ligands in
      the signal-sending cells. Four E3 ubiquitin ligases, Mind bomb (Mib) 1, Mib2,
      Neuralized (Neur) 1, and Neur2, regulate the Notch ligands to activate Notch
      signaling, but their roles in lymphocyte development have not been defined. We
      show that Mib1 regulates T and marginal zone B (MZB) cell development in the
      lymphopoietic niches. Inactivation of the Mib1 gene, but not the other E3
      ligases, Mib2, Neur1, and Neur2, abrogated T and MZB cell development. Reciprocal
      bone marrow (BM) transplantation experiments revealed that Mib1 in the thymic and
      splenic niches is essential for T and MZB cell development. Interestingly, when
      BM cells from transgenic Notch reporter mice were transplanted into Mib1-null
      mice, the Notch signaling was abolished in the double-negative thymocytes. In
      addition, the endocytosis of Dll1 was impaired in the Mib1-null microenvironment.
      Moreover, the block in T cell development and the failure of Dll1 endocytosis
      were also observed in coculture system by Mib1 knockdown. Our study reveals that
      Mib1 is the essential E3 ligase in T and MZB cell development, through the
      regulation of Notch ligands in the thymic and splenic microenvironments.

PMID- 18824588
TI  - The mouth of a dense-core vesicle opens and closes in a concerted action
      regulated by calcium and amphiphysin.
AB  - Secretion of hormones and peptides by neuroendocrine cells occurs through fast
      and slow modes of vesicle fusion but the mechanics of these processes are not
      understood. We used interference reflection microscopy to monitor deformations of
      the membrane surface and found that both modes of fusion involve the tightly
      coupled dilation and constriction of the vesicle. The rate of opening is calcium
      dependent and occurs rapidly at concentrations <5 microM. The fast mode of fusion
      is blocked selectively by a truncation mutant of amphiphysin. Vesicles do not
      collapse when fusion is triggered by strontium, rather they remain locked open
      and membrane scission is blocked. In contrast, constriction of the vesicle
      opening continues when endocytosis is blocked by inhibiting the function of
      dynamin. Thus, fast and slow modes of fusion involve similar membrane
      deformations and vesicle closure can be uncoupled from membrane scission.
      Regulation of these processes by calcium and amphiphysin may provide a mechanism
      for controlling the release of vesicle contents.

PMID- 18824589
TI  - ATP inhibition of CLC-1 is controlled by oxidation and reduction.
AB  - The effect of intracellular adenosine triphosphate (ATP) on the "common gating"
      of the CLC-1 chloride channel has been studied by several laboratories with
      controversial results. Our previous study on the channel expressed in Xenopus
      oocytes using excised inside-out patch-clamp methods showed a robust effect of
      ATP in shifting the open probability curve of the common gate toward more
      depolarizing voltages (Tseng, P.Y., B. Bennetts, and T.Y. Chen. 2007. J. Gen.
      Physiol. 130:217-221). The results were consistent with those from studying the
      channel expressed in mammalian cells using whole cell recording methods
      (Bennetts, B., M.W. Parker, and B.A. Cromer. 2007. J. Biol. Chem. 282:32780
      32791). However, a recent study using excised-patch recording methods for
      channels expressed in Xenopus oocytes reported that ATP had no direct effect on
      CLC-1 (Zifarelli, G., and M. Pusch. 2008. J. Gen. Physiol. 131:109-116). Here, we
      report that oxidation of CLC-1 may be the culprit underlying the controversy.
      When patches were excised from mammalian cells, the sensitivity to ATP was lost
      quickly--within 2-3 min. This loss of ATP sensitivity could be prevented or
      reversed by reducing agents. On the other hand, CLC-1 expressed in Xenopus
      oocytes lost the ATP sensitivity when patches were treated with oxidizing
      reagents. These results suggest a novel view in muscle physiology that the
      mechanisms controlling muscle fatigability may include the oxidation of CLC-1.

PMID- 18824590
TI  - Luminal Mg2+, a key factor controlling RYR2-mediated Ca2+ release: cytoplasmic
      and luminal regulation modeled in a tetrameric channel.
AB  - In cardiac muscle, intracellular Ca(2+) and Mg(2+) are potent regulators of
      calcium release from the sarcoplasmic reticulum (SR). It is well known that the
      free [Ca(2+)] in the SR ([Ca(2+)](L)) stimulates the Ca(2+) release channels
      (ryanodine receptor [RYR]2). However, little is known about the action of luminal
      Mg(2+), which has not been regarded as an important regulator of Ca(2+) release.
      The effects of luminal Ca(2+) and Mg(2+) on sheep RYR2 were measured in lipid
      bilayers. Cytoplasmic and luminal Ca(2+) produced a synergistic increase in the
      opening rate of RYRs. A novel, high affinity inhibition of RYR2 by luminal Mg(2+)
      was observed, pointing to an important physiological role for luminal Mg(2+) in
      cardiac muscle. At diastolic [Ca(2+)](C), luminal Mg(2+) inhibition was voltage
      independent, with K(i) = 45 microM at luminal [Ca(2+)] ([Ca(2+)](L)) = 100
      microM. Luminal and cytoplasmic Mg(2+) inhibition was alleviated by increasing
      [Ca(2+)](L) or [Ca(2+)](C). Ca(2+) and Mg(2+) on opposite sides of the bilayer
      exhibited competitive effects on RYRs, indicating that they can compete via the
      pore for common sites. The data were accurately fitted by a model based on a
      tetrameric RYR structure with four Ca(2+)-sensing mechanisms on each subunit:
      activating luminal L-site (40-microM affinity for Mg(2+) and Ca(2+)), cytoplasmic
      A-site (1.2 microM for Ca(2+) and 60 microM for Mg(2+)), inactivating cytoplasmic
      I(1)-site (approximately 10 mM for Ca(2+) and Mg(2+)), and I(2)-site (1.2 microM
      for Ca(2+)). Activation of three or more subunits will cause channel opening.
      Mg(2+) inhibition occurs primarily by Mg(2+) displacing Ca(2+) from the L- and A
      sites, and Mg(2+) fails to open the channel. The model predicts that under
      physiological conditions, SR load-dependent Ca(2+) release (1) is mainly
      determined by Ca(2+) displacement of Mg(2+) from the L-site as SR loading
      increases, and (2) depends on the properties of both luminal and cytoplasmic
      activation mechanisms.

PMID- 18824591
TI  - Gating pore currents in DIIS4 mutations of NaV1.4 associated with periodic
      paralysis: saturation of ion flux and implications for disease pathogenesis.
AB  - S4 voltage-sensor mutations in CaV1.1 and NaV1.4 channels cause the human muscle
      disorder hypokalemic periodic paralysis (HypoPP). The mechanism whereby these
      mutations predispose affected sarcolemma to attacks of sustained depolarization
      and loss of excitability is poorly understood. Recently, three HypoPP mutations
      in the domain II S4 segment of NaV1.4 were shown to create accessory ionic
      permeation pathways, presumably extending through the aqueous gating pore in
      which the S4 segment resides. However, there are several disparities between
      reported gating pore currents from different investigators, including differences
      in ionic selectivity and estimates of current amplitude, which in turn have
      important implications for the pathological relevance of these aberrant currents.
      To clarify the features of gating pore currents arising from different DIIS4
      mutants, we recorded gating pore currents created by HypoPP missense mutations at
      position R666 in the rat isoform of Nav1.4 (the second arginine from the outside,
      at R672 in human NaV1.4). Extensive measurements were made for the index
      mutation, R666G, which created a gating pore that was permeable to K(+) and
      Na(+). This current had a markedly shallow slope conductance at hyperpolarized
      voltages and robust inward rectification, even when the ionic gradient strongly
      favored outward ionic flow. These characteristics were accounted for by a barrier
      model incorporating a voltage-gated permeation pathway with a single cation
      binding site oriented near the external surface of the electrical field. The
      amplitude of the R666G gating pore current was similar to the amplitude of a
      previously described proton-selective current flowing through the gating pore in
      rNaV1.4-R663H mutant channels. Currents with similar amplitude and cation
      selectivity were also observed in R666S and R666C mutant channels, while a proton
      selective current was observed in R666H mutant channels. These results add
      support to the notion that HypoPP mutations share a common biophysical profile
      comprised of a low-amplitude inward current at the resting potential that may
      contribute to the pathological depolarization during attacks of weakness.

PMID- 18824592
TI  - Steady-state function of the ubiquitous mammalian Na/H exchanger (NHE1) in
      relation to dimer coupling models with 2Na/2H stoichiometry.
AB  - We describe the steady-state function of the ubiquitous mammalian Na/H exchanger
      (NHE)1 isoform in voltage-clamped Chinese hamster ovary cells, as well as other
      cells, using oscillating pH-sensitive microelectrodes to quantify proton fluxes
      via extracellular pH gradients. Giant excised patches could not be used as
      gigaseal formation disrupts NHE activity within the patch. We first analyzed
      forward transport at an extracellular pH of 8.2 with no cytoplasmic Na (i.e.,
      nearly zero-trans). The extracellular Na concentration dependence is sigmoidal at
      a cytoplasmic pH of 6.8 with a Hill coefficient of 1.8. In contrast, at a
      cytoplasmic pH of 6.0, the Hill coefficient is <1, and Na dependence often
      appears biphasic. Results are similar for mouse skin fibroblasts and for an
      opossum kidney cell line that expresses the NHE3 isoform, whereas NHE1(-/-) skin
      fibroblasts generate no proton fluxes in equivalent experiments. As proton flux
      is decreased by increasing cytoplasmic pH, the half-maximal concentration
      (K(1/2)) of extracellular Na decreases less than expected for simple consecutive
      ion exchange models. The K(1/2) for cytoplasmic protons decreases with increasing
      extracellular Na, opposite to predictions of consecutive exchange models. For
      reverse transport, which is robust at a cytoplasmic pH of 7.6, the K(1/2) for
      extracellular protons decreases only a factor of 0.4 when maximal activity is
      decreased fivefold by reducing cytoplasmic Na. With 140 mM of extracellular Na
      and no cytoplasmic Na, the K(1/2) for cytoplasmic protons is 50 nM (pH 7.3; Hill
      coefficient, 1.5), and activity decreases only 25% with extracellular
      acidification from 8.5 to 7.2. Most data can be reconstructed with two very
      different coupled dimer models. In one model, monomers operate independently at
      low cytoplasmic pH but couple to translocate two ions in "parallel" at alkaline
      pH. In the second "serial" model, each monomer transports two ions, and
      translocation by one monomer allosterically promotes translocation by the paired
      monomer in opposite direction. We conclude that a large fraction of mammalian
      Na/H activity may occur with a 2Na/2H stoichiometry.

PMID- 18824593
TI  - Single-agent lenalidomide induces complete remission of acute myeloid leukemia in
      patients with isolated trisomy 13.
AB  - Patients with acute myeloid leukemia (AML) frequently fail chemotherapy due to
      refractory disease, relapse, or toxicity. Among older AML patients (age > 60
      years), there are few long-term survivors. Lenalidomide is a candidate for study
      in AML based on its clinical activity in a related disorder, myelodysplastic
      syndrome (MDS), with the 5q- chromosomal abnormality. We report induction of
      sustained morphologic and cytogenetic complete remission in 2 older AML patients
      treated with high-dose, single-agent lenalidomide; each patient had trisomy 13 as
      the sole cytogenetic abnormality. We show for the first time that lenalidomide
      has clinical activity in this poor-risk cytogenetic subset of AML. The clinical
      trials described in this paper have been registered with www.clinicaltrials.gov
      under identifiers NCT00466895 and NCT00546897.

PMID- 18824594
TI  - Depletion of autoreactive immunologic memory followed by autologous hematopoietic
      stem cell transplantation in patients with refractory SLE induces long-term
      remission through de novo generation of a juvenile and tolerant immune system.
AB  - Clinical trials have indicated that immunoablation followed by autologous
      hematopoietic stem cell transplantation (ASCT) has the potential to induce
      clinical remission in patients with refractory systemic lupus erythematosus
      (SLE), but the mechanisms have remained unclear. We now report the results of a
      single-center prospective study of long-term immune reconstitution after ASCT in
      7 patients with SLE. The clinical remissions observed in these patients are
      accompanied by the depletion of autoreactive immunologic memory, reflected by the
      disappearance of pathogenic anti-double-stranded DNA (dsDNA) antibodies and
      protective antibodies in serum and a fundamental resetting of the adaptive immune
      system. The latter comprises recurrence of CD31(+)CD45RA(+)CD4(+) T cells (recent
      thymic emigrants) with a doubling in absolute numbers compared with age-matched
      healthy controls at the 3-year follow-up (P = .016), the regeneration of thymic
      derived FoxP3(+) regulatory T cells, and normalization of peripheral T-cell
      receptor (TCR) repertoire usage. Likewise, responders exhibited normalization of
      the previously disturbed B-cell homeostasis with numeric recovery of the naive B
      cell compartment within 1 year after ASCT. These data are the first to
      demonstrate that both depletion of the autoreactive immunologic memory and a
      profound resetting of the adaptive immune system are required to reestablish self
      tolerance in SLE.

PMID- 18824595
TI  - Elevated growth differentiation factor 15 expression in patients with congenital
      dyserythropoietic anemia type I.
AB  - Congenital dyserythropoietic anemia (CDA) is a rare group of red blood cell
      disorders characterized by ineffective erythropoiesis and increased iron
      absorption. To determine whether growth differentation factor 15 (GDF15) hyper
      expression is associated with the ineffective erythropoiesis and iron-loading
      complications of CDA type I (CDA I), GDF15 levels and other markers of
      erythropoiesis and iron overload were studied in blood from 17 CDA I patients.
      Significantly higher levels of GDF15 were detected among the CDA I patients (10
      239 +/- 3049 pg/mL) compared with healthy volunteers (269 +/- 238 pg/mL). In
      addition, GDF15 correlated significantly with several erythropoietic and iron
      parameters including Hepcidin-25, Ferritin, and Hepcidin-25/Ferritin ratios.
      These novel results suggest that CDA I patients express very high levels of serum
      GDF15, and that GDF15 contributes to the inappropriate suppression of hepcidin
      with subsequent secondary hemochromatosis.

PMID- 18824596
TI  - Critical role of scavenger receptor-BI-expressing bone marrow-derived endothelial
      progenitor cells in the attenuation of allograft vasculopathy after human apo A-I
      transfer.
AB  - Allograft vasculopathy is the leading cause of death in patients with heart
      transplantation. Accelerated endothelial regeneration mediated by enhanced
      endothelial progenitor cell (EPC) incorporation may attenuate the development of
      allograft vasculopathy. We investigated the hypothesis that modulation of EPC
      biology and attenuation of allograft vasculopathy by increased high-density
      lipoprotein cholesterol after human apo A-I (AdA-I) transfer requires scavenger
      receptor (SR)-BI expression in bone marrow-derived EPCs. After AdA-I transfer,
      the number of circulating EPCs increased 2.0-fold (P < .001) at different time
      points in C57BL/6 mice transplanted with SR-BI(+/+) bone marrow but remained
      unaltered in mice with SR-BI(-/-) bone marrow. The effect of high-density
      lipoprotein on EPC migration in vitro requires signaling via SR-BI and
      extracellular signal-regulated kinases and is dependent on increased nitric oxide
      (NO) production in EPCs. Human apo A-I transfer 2 weeks before paratopic artery
      transplantation reduced intimal area at day 21 3.7-fold (P < .001) in mice with
      SR-BI(+/+) bone marrow but had no effect in mice with SR-BI(-/-) bone marrow. AdA
      I transfer potently stimulated EPC incorporation and accelerated endothelial
      regeneration in chimeric SR-BI(+/+) mice but not in chimeric SR-BI(-/-) mice. In
      conclusion, human apo A-I transfer accelerates endothelial regeneration mediated
      via SR-BI expressing bone marrow-derived EPCs, thereby preventing allograft
      vasculopathy.

PMID- 18824597
TI  - Androgen depletion increases the efficacy of bone marrow transplantation in
      ameliorating experimental autoimmune encephalomyelitis.
AB  - Bone marrow transplantation (BMT) potentially represents a novel therapy for the
      amelioration and even cure for multiple sclerosis (MS). It has important
      advantages over immunosuppressive drug treatments because, while effecting broad
      based ablation of the immune system and autoreactive cells, it provides an
      important means for overcoming the resultant immunodeficiency, while possibly
      restoring self-tolerance. However, both of these benefits are predicated on a
      functional thymus that undergoes profound age-induced atrophy from puberty.
      Reversal of thymic atrophy has been achieved by several procedures, including
      removal of sex steroids by surgical or chemical (LHRH agonist) castration. Using
      a murine model of MS, experimental autoimmune encephalomyelitis (EAE), we
      combined BMT with androgen depletion to induce immune regeneration, and
      investigated the kinetics of increased thymic function on immune reconstitution
      and disease reduction. We show that androgen depletion significantly increased
      the efficacy of BMT to ameliorate the clinical signs of EAE while concurrently
      restoring the periphery with increased naive and regulatory lymphocytic
      populations. Upon rechallenge, mice with a regenerated thymus had a slower onset
      of clinical symptoms compared with mice undergoing BMT only. These results
      suggest that thymic regeneration strategies may be used as a complement to
      conventional BMT protocols for the treatment of MS.

PMID- 18824598
TI  - The Amot/Patj/Syx signaling complex spatially controls RhoA GTPase activity in
      migrating endothelial cells.
AB  - Controlled regulation of Rho GTPase activity is an essential component mediating
      growth factor-stimulated migration. We have previously shown that angiomotin
      (Amot), a membrane-associated scaffold protein, plays a critical role during
      vascular patterning and endothelial migration during embryogenesis. However, the
      signaling pathways by which Amot controls directional migration are not known.
      Here we have used peptide pull-down and yeast 2-hybrid (Y2H) screening to
      identify proteins that interact with the C-terminal PDZ-binding motifs of Amot
      and its related proteins AmotL1 and 2. We report that Amot and its related
      proteins bind to the RhoA GTPase exchange factor (RhoGEF) protein Syx. We show
      that Amot forms a ternary complex together with Patj (or its paralogue Mupp1) and
      Syx. Using FRET analysis, we provide evidence that Amot controls targeting of
      RhoA activity to lamellipodia in vitro. We also report that, similar to Amot,
      morpholino knockdown of Syx in zebrafish results in inhibition of migration of
      intersegmental arteries. Taken together, our results indicate that the
      directional migration of capillaries in the embryo is governed by the
      Amot:Patj/Mupp1:Syx signaling that controls local GTPase activity.

PMID- 18824599
TI  - Triggering TLR7 in mice induces immune activation and lymphoid system disruption,
      resembling HIV-mediated pathology.
AB  - Chronic immune activation is a major cause for progressive immunodeficiency in
      human immunodeficiency virus type-1 (HIV) infection. The underlying trigger,
      however, remains largely unknown. HIV single-stranded RNA is a potent immune
      activator by triggering Toll-like receptor (TLR) 7/8. Thus, we hypothesized that
      sustained TLR7 triggering induces chronic immune activation and thereby
      contributes to progressive immunodeficiency. We used the synthetic compound R848
      or a mixture of uridine-rich HIV single-stranded (ss) RNA oligonucleotides--both
      are potent TLR7/8 agonists--to explore the effects of sustained TLR7 triggering
      on the murine lymphoid system. Sustained TLR7 triggering induced an
      immunopathology reminiscent of progressive lymphoid destruction in HIV disease;
      we observed lymphopenia, elevated proinflammatory cytokines, splenomegaly,
      contracted lymphoid subsets, and lymphoid microarchitecture alteration with
      reduced marginal zone B-lymphocytes. Upon exposure to inactivated vesiculo
      stomatitis virus, antibody production was abolished, although splenic lymphocytes
      were activated and total IgG was elevated. Our data imply that HIV itself may
      directly contribute to immune activation and dysfunction by stimulating TLR7.
      Thus, manipulation of TLR7 signaling may be a potential strategy to reduce
      chronic hyper-immune activation and, thereby, disease progression in HIV
      infection.

PMID- 18824600
TI  - A key role for G-CSF-induced neutrophil production and trafficking during
      inflammatory arthritis.
AB  - We have previously shown that G-CSF-deficient (G-CSF(-/-)) mice are markedly
      protected from collagen-induced arthritis (CIA), which is the major murine model
      of rheumatoid arthritis, and now investigate the mechanisms by which G-CSF can
      promote inflammatory disease. Serum G-CSF levels were significantly elevated
      during CIA. Reciprocal bone marrow chimeras using G-CSF(-/-), G-CSFR(-/-), and
      wild-type (WT) mice identified nonhematopoietic cells as the major producers of G
      CSF and hematopoietic cells as the major responders to G-CSF during CIA.
      Protection against CIA was associated with relative neutropenia. Depletion of
      neutrophils or blockade of the neutrophil adhesion molecule, Mac-1, dramatically
      attenuated the progression of established CIA in WT mice. Intravital microscopy
      of the microcirculation showed that both local and systemic administration of G
      CSF significantly increased leukocyte trafficking into tissues in vivo. G-CSF
      induced trafficking was Mac-1 dependent, and G-CSF up-regulated CD11b expression
      on neutrophils. Multiphoton microscopy of synovial vessels in the knee joint
      during CIA revealed significantly fewer adherent Gr-1(+) neutrophils in G-CSF(-/
      ) mice compared with WT mice. These data confirm a central proinflammatory role
      for G-CSF in the pathogenesis of inflammatory arthritis, which may be due to the
      promotion of neutrophil trafficking into inflamed joints, in addition to G-CSF
      induced neutrophil production.

PMID- 18824601
TI  - Nifuroxazide inhibits survival of multiple myeloma cells by directly inhibiting
      STAT3.
AB  - Constitutive activation of the transcription factor STAT3 contributes to the
      pathogenesis of many cancers, including multiple myeloma (MM). Since STAT3 is
      dispensable in most normal tissue, targeted inhibition of STAT3 is an attractive
      therapy for patients with these cancers. To identify STAT3 inhibitors, we
      developed a transcriptionally based assay and screened a library of compounds
      known to be safe in humans. We found the drug nifuroxazide to be an effective
      inhibitor of STAT3 function. Nifuroxazide inhibits the constitutive
      phosphorylation of STAT3 in MM cells by reducing Jak kinase autophosphorylation,
      and leads to down-regulation of the STAT3 target gene Mcl-1. Nifuroxazide causes
      a decrease in viability of primary myeloma cells and myeloma cell lines
      containing STAT3 activation, but not normal peripheral blood mononuclear cells.
      Although bone marrow stromal cells provide survival signals to myeloma cells,
      nifuroxazide can overcome this survival advantage. Reflecting the interaction of
      STAT3 with other cellular pathways, nifuroxazide shows enhanced cytotoxicity when
      combined with either the histone deacetylase inhibitor depsipeptide or the MEK
      inhibitor UO126. Therefore, using a mechanistic-based screen, we identified the
      clinically relevant drug nifuroxazide as a potent inhibitor of STAT signaling
      that shows cytotoxicity against myeloma cells that depend on STAT3 for survival.

PMID- 18824602
TI  - Exploring the commonalities between adaptive resources and self-enhancement in
      older adults' comparative judgments of physical activity.
AB  - Objective. This study examines the extent to which optimism, control beliefs and
      motivation, and downward social comparison contribute independently to the
      maintenance of older adults positive self-evaluations in a functional domain.
      Method. Adaptive resources/strategies and life satisfaction were measured in
      personal interviews with 164 community-dwelling older adults. Participants judged
      their physical activity compared with the average person of their age and wore an
      accelerometer for 24 hours. Commonality analysis was used to estimate unique
      versus shared effects of the resource/strategy variables on a residual measure of
      self-enhancement, obtained by adjusting the comparative judgments for
      participants' age and objectively measured physical activity. Results. Self
      enhancement was positively related to life satisfaction. Perceived control and
      optimism had shared positive effects on self-enhancement, whereas downward social
      comparison had a unique positive effect. Discussion. Self-enhancement of physical
      activity plays a part in at least two adaptive profiles with implications for
      older adults' well-being and health.

PMID- 18824603
TI  - Activity of indenoisoquinolines against African trypanosomes.
AB  - African trypanosomiasis (sleeping sickness), caused by protozoan Trypanosoma
      brucei species, is a debilitating disease that is lethal if untreated. Available
      drugs are antiquated, toxic, and compromised by emerging resistance. The
      indenoisoquinolines are a class of noncamptothecin topoisomerase IB poisons that
      are under development as anticancer agents. We tested a variety of
      indenoisoquinolines for their ability to kill T. brucei. Indenoisoquinolines
      proved trypanocidal at submicromolar concentrations in vitro. Structure-activity
      analysis yielded motifs that enhanced potency, including alkylamino substitutions
      on N-6, methoxy groups on C-2 and C-3, and a methylenedioxy bridge between C-8
      and C-9. Detailed analysis of eight water-soluble indenoisoquinolines
      demonstrated that in trypanosomes the compounds inhibited DNA synthesis and acted
      as topoisomerase poisons. Testing these compounds on L1210 mouse leukemia cells
      revealed that all eight were more effective against trypanosomes than against
      mammalian cells. In preliminary in vivo experiments one compound delayed
      parasitemia and extended survival in mice subjected to a lethal trypanosome
      challenge. The indenoisoquinolines provide a promising lead for the development
      of drugs against sleeping sickness.

PMID- 18824604
TI  - Novel genetic determinants of low-level aminoglycoside resistance in Pseudomonas
      aeruginosa.
AB  - Pseudomonas aeruginosa strains isolated from patients with persistent lung
      infections and cystic fibrosis have been found to gradually develop
      aminoglycoside resistance over time. The aim of this study was to identify
      potential contributors to low-level aminoglycoside resistance, which may cause
      such graduated increases in resistance. The Harvard P. aeruginosa PA14
      nonredundant library, consisting of approximately 5,800 mutants, was screened for
      twofold or greater increases in tobramycin resistance. Mutants carrying mutations
      in a total of 135 unique genes were identified and confirmed to have reduced
      susceptibility to tobramycin. Many of these genes were involved predominantly in
      energy metabolism; however, most of these mutants did not exhibit growth defects
      under the conditions tested, although some exhibited the small-colony phenotype
      and/or defects in growth under anaerobic conditions. Lipopolysaccharide mutants
      were also identified, and it was found that tobramycin had a reduced ability to
      permeabilize the outer membranes of these mutants. The results of this study
      emphasize the complexity of the interactions that tobramycin may have within the
      bacterial cell and introduce a large number of novel genes which may play a role
      in tobramycin resistance.

PMID- 18824605
TI  - Preclinical characteristics of the hepatitis C virus NS3/4A protease inhibitor
      ITMN-191 (R7227).
AB  - Future treatments for chronic hepatitis C virus (HCV) infection are likely to
      include agents that target viral components directly. Here, the preclinical
      characteristics of ITMN-191, a peptidomimetic inhibitor of the NS3/4A protease of
      HCV, are described. ITMN-191 inhibited a reference genotype 1 NS3/4A protein in a
      time-dependent fashion, a hallmark of an inhibitor with a two-step binding
      mechanism and a low dissociation rate. Under preequilibrium conditions, 290 pM
      ITMN-191 half-maximally inhibited the reference NS3/4A protease, but a 35,000
      fold-higher concentration did not appreciably inhibit a panel of 79 proteases,
      ion channels, transporters, and cell surface receptors. Subnanomolar biochemical
      potency was maintained against NS3/4A derived from HCV genotypes 4, 5, and 6,
      while single-digit nanomolar potency was observed against NS3/4A from genotypes
      2b and 3a. Dilution of a preformed enzyme inhibitor complex indicated ITMN-191
      remained bound to and inhibited NS3/4A for more than 5 h after its initial
      association. In cell-based potency assays, half-maximal reduction of genotype 1b
      HCV replicon RNA was afforded by 1.8 nM; 45 nM eliminated the HCV replicon from
      cells. Peginterferon alfa-2a displayed a significant degree of antiviral synergy
      with ITMN-191 and reduced the concentration of ITMN-191 required for HCV replicon
      elimination. A 30-mg/kg of body weight oral dose administered to rats or monkeys
      yielded liver concentrations 12 h after dosing that exceeded the ITMN-191
      concentration required to eliminate replicon RNA from cells. These preclinical
      characteristics compare favorably to those of other inhibitors of NS3/4A in
      clinical development and therefore support the clinical investigation of ITMN-191
      for the treatment of chronic hepatitis C.

PMID- 18824606
TI  - In vitro activity of the antifungal plant defensin RsAFP2 against Candida
      isolates and its in vivo efficacy in prophylactic murine models of candidiasis.
AB  - We show that RsAFP2, a plant defensin that interacts with fungal
      glucosylceramides, is active against Candida albicans, inhibits to a lesser
      extent other Candida species, and is nontoxic to mammalian cells. Moreover,
      glucosylceramide levels in Candida species correlate with RsAFP2 sensitivity. We
      found RsAFP2 prophylactically effective against murine candidiasis.

PMID- 18824607
TI  - Inhibition of Toxoplasma gondii by indirubin and tryptanthrin analogs.
AB  - New drugs are needed for treatment of Toxoplasma gondii infections. We tested
      derivatives of principles found in Isatis indigotica for in vitro efficacy
      against T. gondii infection. Indirubin-3'-oxime analogs showed modest micromolar
      activity, while tryptanthrin derivatives displayed 50% inhibitory doses in the
      low nanomolar range. Tryptanthrins have potential as anti-Toxoplasma infection
      therapeutics.

PMID- 18824608
TI  - Pharmacokinetic and safety evaluation of BILR 355, a second-generation
      nonnucleoside reverse transcriptase inhibitor, in healthy volunteers.
AB  - BILR 355 is a second-generation nonnucleoside reverse transcriptase inhibitor
      (NNRTI) under clinical development for the treatment of human immunodeficiency
      virus infection, particularly in those who harbor virus resistant to the
      currently available NNRTIs. Two single-center, double-blinded, placebo
      controlled, parallel dose-escalation studies were conducted to evaluate the
      pharmacokinetics and safety of oral BILR 355 administration alone and after
      coadministration with ritonavir (RTV) at 100 mg. Following a single dose of BILR
      355 in oral solution, the mean half life (t(1/2)) was 2 to 4 h, with peak
      concentrations occurring at 0.5 to 1 h postadministration. The mean apparent
      clearance (CL/F) ranged from 79.2 to 246 liters/h for administered doses of 12.5
      mg to 100 mg. This observed nonlinearity in CL/F resulted from the increased
      bioavailability attributed to a saturated absorption and/or elimination process
      at higher doses. In contrast, after the coadministration of single doses of 5 mg
      to 87.5 mg of BILR 355 with RTV, the mean CL/F ranged from 5.88 to 8.47 liters/h.
      Over the dose range (5 to 87.5 mg) studied, systemic BILR 355 exposures were
      approximately proportional to the doses administered when they were
      coadministered with RTV. With RTV coadministration, the mean t(1/2) increased to
      10 to 16 h, and the mean time of the maximum concentration in plasma lengthened
      to 1.5 to 5 h. Compared to the values for BILR 355 given alone, the mean area
      under the concentration-time curve from time zero to infinity, the maximum
      concentration in plasma, and the t(1/2) of BILR 355 achieved after
      coadministration with RTV increased 15- to 30-fold, 2- to 5-fold, and 3- to 5
      fold, respectively. In both studies, BILR 355 appeared to be safe and well
      tolerated in healthy volunteers when the outcomes in the treated volunteers were
      compared with those in the placebo group.

PMID- 18824609
TI  - Complex ciprofloxacin resistome revealed by screening a Pseudomonas aeruginosa
      mutant library for altered susceptibility.
AB  - Pseudomonas aeruginosa offers substantial therapeutic challenges due to its high
      intrinsic resistance to many antibiotics and its propensity to develop mutational
      and/or adaptive resistance. The PA14 comprehensive mutant library was screened
      for mutants exhibiting either two- to eightfold increased susceptibilities
      (revealing genes involved in intrinsic resistance) or decreased susceptibilities
      (mutational resistance) to the fluoroquinolone ciprofloxacin. Thirty-five and 79
      mutants with increased and decreased susceptibilities, respectively, were
      identified, as confirmed by broth dilution.

PMID- 18824610
TI  - Antimony resistance and trypanothione in experimentally selected and clinical
      strains of Leishmania panamensis.
AB  - The participation of trypanothione in clinical and experimental antimony (Sb)
      resistance in Leishmania panamensis was examined by using specific inhibitors.
      Buthionine sulfoximine (BSO) significantly reversed the resistance to trivalent
      Sb (Sb(III)) of promastigotes of experimentally derived Sb-resistant lines,
      supporting the participation of a trypanothione-mediated mechanism of resistance.
      In contrast, promastigotes of strains isolated at the time of clinical treatment
      failure and resistant to pentavalent Sb (Sb(V)) as intracellular amastigotes were
      not cross resistant to Sb(III), and BSO had little or no effect on
      susceptibility. Difluoromethylornithine did not alter the Sb(III)
      susceptibilities of experimentally selected lines or clinical strains. The
      mechanisms of acquired resistance emerging in clinical settings may differ from
      those selected by in vitro exposure to Sb.

PMID- 18824611
TI  - Serial daptomycin selection generates daptomycin-nonsusceptible Staphylococcus
      aureus strains with a heterogeneous vancomycin-intermediate phenotype.
AB  - In order to better understand the mechanism of daptomycin resistance, we
      generated a daptomycin-nonsusceptible derivative strain, strain 10*3d1 (MIC = 3.0
      microg/ml), by in vitro exposure of methicillin-resistant Staphylococcus aureus
      strain N315DeltaIP (MIC = 0.5 microg/ml) to daptomycin. We also obtained a
      daptomycin-susceptible phenotypic revertant strain, strain 10*3d1-10 (MIC = 1.0
      microg/ml), by passaging 10*3d1 in drug-free medium for 10 days. The resultant
      triple-isogenic strains were analyzed for their phenotypes and gene expression by
      microarray analysis. No significant differences in the membrane fluidities of
      10*3d1 and 10*3d1-10 compared to the membrane fluidity of N315DeltaIP were
      observed. Resistant strain 10*3d1 had the highest membrane potential, followed by
      strains 10*3d1-10 and N315DeltaIP. The vancomycin and teicoplanin MICs also
      increased. Teichoic acid genes (tagA, tagG), mprF encoding lysyl
      phosphatidylglycerol, and cls encoding cardiolipin synthase were downregulated in
      10*3d1 and 10*3d1-10. The vraF and vraG genes, which encode ATP binding cassette
      transporter proteins, were upregulated in 10*3d1. The vraSR two-component
      regulatory system was upregulated, and electron microscopy revealed that the cell
      wall of 10*3d1 was significantly thicker than that of the parental strain. Taken
      together, daptomycin exposure selected a daptomycin-nonsusceptible strain with a
      phenotype similar to that of heterogeneous vancomycin-intermediate S. aureus and
      a transcription profile that partially overlapped that of heterogeneous
      vancomycin-intermediate S. aureus.

PMID- 18824612
TI  - Therapeutic activity of an anti-idiotypic antibody-derived killer peptide against
      influenza A virus experimental infection.
AB  - The in vitro and in vivo activities of a killer decapeptide (KP) against
      influenza A virus is described, and the mechanisms of action are suggested. KP
      represents the functional internal image of a yeast killer toxin that proved to
      exert antimicrobial and anti-human immunodeficiency virus type 1 (HIV-1)
      activities. Treatment with KP demonstrated a significant inhibitory activity on
      the replication of two strains of influenza A virus in different cell lines, as
      evaluated by hemagglutination, hemadsorption, and plaque assays. The complete
      inhibition of virus particle production and a marked reduction of the synthesis
      of viral proteins (membrane protein and hemagglutinin, in particular) were
      observed at a KP concentration of 4 microg/ml. Moreover, KP administered
      intraperitoneally at a dose of 100 microg/mice once a day for 10 days to
      influenza A/NWS/33 (H1N1) virus-infected mice improved the survival of the
      animals by 40% and significantly decreased the viral titers in their lungs.
      Overall, KP appears to be the first anti-idiotypic antibody-derived peptide that
      displays inhibitory activity and that has a potential therapeutic effect against
      pathogenic microorganisms, HIV-1, and influenza A virus by different mechanisms
      of action.

PMID- 18824613
TI  - Selectivity of agonists for the active state of M1 to M4 muscarinic receptor
      subtypes.
AB  - We measured the intrinsic relative activity (RA(i)) of muscarinic agonists to
      detect possible selectivity for receptor subtypes and signaling pathways. RA(i)
      is a relative measure of the microscopic affinity constant of an agonist for the
      active state of a GPCR expressed relative to that of a standard agonist. First,
      we estimated RA(i) values for a panel of agonists acting at the M(4) muscarinic
      receptor coupled to three distinct G-protein pathways: G(i) inhibition of cAMP
      accumulation, G(s) stimulation of cAMP accumulation, and G alpha(15) stimulation
      of phosphoinositide hydrolysis. Our results show similar RA(i) values for each
      agonist, suggesting that the same active state of the M(4) receptor triggers the
      activation of the three G proteins. We also estimated RA(i) values for agonists
      across M(1) to M(4) muscarinic subtypes stably transfected in Chinese hamster
      ovary cells. Our results show selectivity of McN-A-343 [4-I-[3
      chlorophenyl]carbamoyloxy)-2-butynyltrimethylammnonium chloride] for the M(1) and
      M(4) subtypes and selectivity of pilocarpine for the M(1) and M(3) subtypes. The
      other agonists tested lacked marked selectivity among M(1) to M(4) receptors.
      Finally, we estimated RA(i) values from published literature on M(1), M(2), and
      M(3) muscarinic responses and obtained results consistent with our own studies.
      Our results show that the RA(i) estimate is a useful receptor-dependent measure
      of agonist activity.

PMID- 18824614
TI  - Denialism undermines AIDS prevention in sub-Saharan Africa.
AB  - Some denialists, widely reviled, contend that HIV does not cause AIDS. Other
      denialists, widely respected, contend that HIV transmits so poorly through trace
      blood exposures that iatrogenic infections are rare. This second group of
      denialists has had a corrosive effect on public health and HIV programmes in sub
      Saharan Africa. Guided by this second group of denialists, no African government
      has investigated unexplained HIV infections. Denialists have withheld and ignored
      research findings showing that non-sexual risks account for substantial
      proportions of HIV infections in Africa. Denialists have promoted invasive
      procedures for HIV prevention in Africa--injections for sexually transmitted
      infections, and adult male circumcision--without addressing unreliable
      sterilization of reused instruments. By denying that health care causes more than
      rare infections, denialists blame (stigmatize) HIV-positive African adults for
      causing their own infections through sexual behaviour. Denialism must be overcome
      to ensure safe health care and to combat HIV-related stigma in Africa.

PMID- 18824615
TI  - Sexually transmitted infections among brothel-based sex workers in Tel-Aviv area,
      Israel: high prevalence of pharyngeal gonorrhoea.
AB  - Sex workers play a major role in spreading sexually transmitted infections
      (STIs). We studied the prevalence rates and risk factors for STIs among 300
      brothel-based sex workers in Tel-Aviv. Throat swabs were cultured for Neisseria
      gonorrhoeae, urine samples were tested by polymerase chain reaction (PCR) for
      Chlamydia trachomatis and N. gonorrhoeae, and sera were tested for syphilis,
      human immunodeficiency virus (HIV) and type 2 herpes simplex virus (HSV)
      antibodies. N. gonorrhoeae was cultured from throat samples of 9.0% of
      participants; PCR testing of urine was positive for C. trachomatis in 6.3% and
      for N. gonorrhoeae in 5.0%. Syphilis serology was positive (Venereal Disease
      Research Laboratory [VDRL] titres > 1:8) in 1.3% of women, HSV-2-specific
      immunoglobulin G was detected in 60% and HIV serology was positive in a single
      case (0.3%). Having STI was significantly associated with age, number of years in
      Israel, number of clients a week and condom use for vaginal sex. In a
      multivariate analysis, having STI was significantly associated with number of
      clients per week and condom use for vaginal sex. The high prevalence of
      pharyngeal gonorrhoea reflects most probably the expanding demand of clients for
      oral sex and the insufficient condom use in this form of sex.

PMID- 18824616
TI  - Commercial sex and HIV transmission in mature epidemics: a study of five African
      countries.
AB  - The study compares the association between using the services of commercial sex
      workers and male HIV seroprevalence in five African countries: Ghana, Kenya,
      Lesotho, Malawi and Rwanda. The HIV seroprevalence among men who 'ever paid for
      sex' was compared with controls who 'never paid for sex'. Results were based on
      12,929 eligible men, aged 15-59 years, interviewed in Demographic and Health
      Surveys. The odds ratio of HIV seroprevalence associated with ever paying for sex
      was 1.89 (95% confidence interval = 1.57-2.28), with only minor differences by
      country. The results were stable in multivariate analysis after controlling for
      available potential cofactors (data on non-sexual routes of transmission were not
      available). Given the relatively small proportion of men involved, the risk
      attributable to 'ever paying for sex' remained low: 7.1% in univariate analysis
      and 4.4% after adjustment, and it varied among countries (range 1.3-9.4%). These
      results match previous observations that commercial sex seems to play a minor
      role in the spread of HIV in mature epidemics.

PMID- 18824617
TI  - An evaluation of the performance of OraQuick ADVANCE Rapid HIV-1/2 Test in a high
      risk population attending genitourinary medicine clinics in East London, UK.
AB  - To date, no data have been published on the use of OraQuick ADVANCE Rapid HIV-1/2
      Test (OraQuick) in the UK. We report preliminary findings of an ongoing
      evaluation of OraQuick in UK genitourinary (GU) medicine clinics. A total of 820
      samples from patients in high-risk groups for HIV were tested with OraQuick and
      results were compared with standard HIV antibody testing. HIV prevalence (enzyme
      immunoassay [EIA]) was 5.73%, sensitivity of OraQuick was 93.64% (95% CI 82.46
      98.66%), specificity 99.87% (99.28-100%), positive predictive value 97.78% (88.27
      99.94%) and negative predictive value 99.61% (98.87-99.92%). This includes three
      false-negatives considered to be due to observer error and now rectified by
      further training. This has increased test sensitivity to 100%. Our observed test
      performance of OraQuick compares well with EIA and with other rapid tests. We
      believe that simple, non-invasive antibody detection tests such as OraQuick can
      increase HIV testing and diagnosis in UK GU medicine and community settings.

PMID- 18824618
TI  - Cost-effectiveness estimates for antenatal HIV testing in the Netherlands.
AB  - This paper provides an estimation of the lifetime health-care cost of HIV
      infected children and an update of the cost-effectiveness of universal HIV
      screening of pregnant women in Amsterdam (The Netherlands). During 2003-2005, we
      collected data concerning the prevalence of newly diagnosed HIV-infected pregnant
      women in Amsterdam. Also, data on resource utilization and HAART regimen for HIV
      infected children was gathered from a national registry. Using Kaplan-Meier
      survival analysis, we estimated the life-expectancy of a vertically HIV-infected
      child at 19 years, with the corresponding lifetime health-care costs of 179,974
      Euros. HIV-screening of pregnant women could prevent 2.4 HIV transmissions
      annually in Amsterdam, based on an estimated prevalence of nine yet undiagnosed
      HIV-positive pregnant women per 10,000 pregnancies. We show that universal HIV
      screening during pregnancy generates significant net cost savings and health
      benefits in most situations. Universal antenatal HIV screening is justified in
      Amsterdam from a health-economic point of view.

PMID- 18824619
TI  - Azithromycin and moxifloxacin for microbiological cure of Mycoplasma genitalium
      infection: an open study.
AB  - There are no evidence-based guidelines for the treatment of Mycoplasma genitalium
      positive genital infection. In a retrospective survey, we analysed the treatment
      results of patients tested for M. genitalium at Olafia, Unit for Sexual
      Transmitted Diseases in Oslo. Out of 10,109 patients, 452 had a positive
      polymerase chain reaction. Between 72% and 100% of patients in the different
      treatment groups returned for test of cure after four to five weeks. First-line
      treatment with 1 g single dose azithromycin had a recovery rate of 79%. It was as
      effective as an extended five-days' course of azithromycin. Ofloxacin 200 mg
      b.i.d for 10 days cured 56% and moxifloxacin 400 mg o.d. for seven days as either
      second-, third- or fourth-line treatment after azithromycin or ofloxacin failure
      cured 100%. Azithromycin 1 g as a single dose seems to be the best choice of
      treatment for M. genitalium, with moxifloxacin 400 mg x 1 for seven days if
      treatment fails.

PMID- 18824620
TI  - Human papillomavirus type-distribution in condylomata acuminata of mainland
      China: a meta-analysis.
AB  - The aim of this work was to study the human papillomavirus (HPV) type
      distribution in condylomata acuminata (CA) of mainland China and to estimate the
      potential role of HPV prophylactic vaccines for CA in mainland China. Forty-three
      studies using polymerase chain reaction to detect HPV were included in this meta
      analysis, and totally 5247 CA cases and 436 controls were included. The overall
      and type-specific prevalence of HPV 6, 11, 40, 42, 43, 44 were estimated using
      non-conditional logistic regression model. Overall HPV prevalence was 84.2% and
      4.6% for CA and controls, respectively. Estimated HPV types 6, 11, 40, 42
      positive fractions in CA were 54.9%, 41.1%, 2.7% and 2.0%, respectively, and
      exactly 0% for HPV types 43 and 44. HPV 6 and/or 11-positive fractions were 83.0%
      in mainland China. Thus, prophylactic HPV vaccine has the potential to protect up
      to 83% of CA cases in mainland China.

PMID- 18824621
TI  - Factors associated with lack of antiretroviral adherence among adolescents in a
      reference centre in Rio de Janeiro, Brazil.
AB  - The objective of this study was to describe the adherence to antiretroviral
      therapy (ART) among adolescents followed-up in Rio de Janeiro. This cross
      sectional study included all adolescents (aged 10-19 years) followed at Instituto
      de Puericultura e Pediatria Martagao Gesteira and Hospital Universitario
      Clementino Fraga Filho. Adherence was determined by self-report (number of missed
      ART doses in three days prior to the interview). Adherence was categorized as
      taking > or = 95% of the ARTs (adherent), or < 95% (non-adherent). Variables
      related to demographics and treatment were evaluated and if P value < or = 0.15,
      they were selected for a logistic regression analysis. One hundred and one
      adolescents were interviewed. The mean time on ART was 91 months and the mean
      adherence was 94% of this, 21 were non-adherent, and 80 adherent. The risk
      factors associated with non-adherence were: if the patient was not concerned
      about ART, odds ratio (OR) = 3.47 (95% confidence interval [CI] = 1.13-10.68); if
      they do not carry an extra dose of ART, OR = 6.63 (95% CI = 1.73-25.47); if a
      health-care worker taught them how to take ART, OR = 0.27 (95% CI = 0.08-0.93).
      Adherence among adolescents was higher than expected. Factors associated with
      lack of adherence were: interviewees being unaware of ARTs and lack of commitment
      to the treatment. Interventions involving these factors must be evaluated.

PMID- 18824622
TI  - Reactivity in the Venereal Diseases Research Laboratory test and the Mercia IgM
      enzyme immunoassay after treatment of early syphilis.
AB  - The aim of the study was to compare reactivity in the Mercia immunoglobulin M
      enzyme immunoassay (IgM EIA) and the Venereal Disease Research Laboratory (VDRL)
      after treatment of 229 previously untreated patients with early syphilis. At
      three months, the VDRL and the IgM EIA were negative in 41 (38%) and 71 (62%)
      cases, respectively; a four-fold or greater decrease in VDRL titre occurred in
      106 (99%). At six months, the VDRL and the IgM EIA were negative in 45 (48%) and
      69 (71%) patients, respectively; a four-fold or greater decrease in VDRL titre
      occurred in 88 (95%) and an eight-fold or greater decrease in 80 (86%). At 12
      months, the VDRL and the IgM EIA were negative in 35 (70%) and 55 (92%) patients,
      respectively; a four-fold or greater decrease in VDRL titre occurred in 49 (98%)
      and an eight-fold or greater decrease in 47 (94%). The Mercia IgM EIA is as
      sensitive as the VDRL in monitoring treatment of primary syphilis but not as
      sensitive as the finding of a four-fold or eight-fold decrease in VDRL titre in
      patients treated for secondary or early latent infection.

PMID- 18824623
TI  - Herpes simplex virus type 2 infection among commercial sex workers in Kunming,
      Yunnan Province, China.
AB  - A cross-sectional survey was conducted to determine the sociodemographic
      correlates of herpes simplex virus type 2 (HSV-2) infection among male and female
      commercial sex workers in Kunming, Yunnan Province of China. HSV-2 prevalence was
      33.0%, human immunodeficiency virus (HIV) infection was 2.4% and hepatitis C
      virus (HCV) infection was 6.8%. Subjects who were positive for HSV-2 had a
      significantly higher prevalence of HIV infection (5.5% versus 0.9%, P = 0.002;
      odds ratio [OR]: 6.4, P = 0.006) and HCV infection (18.7% versus 2.4%, P < 0.001;
      OR: 7.6, P < 0.001) compared with HSV-2-negative individuals. Risk factors that
      increased the odds of HSV-2 infection were HIV infection, HCV infection, being
      female, and having a steady sex partner within the last six months (P < or =
      0.01). In a multivariate analysis, being female (OR: 6.6, P < 0.001), having HCV
      infection (OR: 5.9, P < 0.001) and having a sex partner within the last six
      months (OR: 2.2, P < 0.05) showed greater odds of being infected with HSV-2. A
      strong relationship was found between HSV-2, HIV and HCV infections.

PMID- 18824624
TI  - Gay men who engage in substance use and sexual risk behaviour: a dual-risk group
      with unique characteristics.
AB  - 'Recreational' substances used among men having sex with men, and their
      association with risky unprotected anal intercourse (RUAI) were examined--for the
      first time in Israel--in an internet-based questionnaire assessing knowledge,
      practices and motivation. Between March and May 2005, 2873 participants completed
      the entire questionnaire. Of the total, 669 (23%) reported RUAI during the last
      six months, and 1319 (46%) used substances during sex. Use of substance was
      significantly higher among those performing RUAI than those who did not (31.5%
      versus 26.4%, P=0.03). Involvement in both substance use and RUAI was reported by
      366 participants (13%). HIV rates were higher in this dual-risk group (P<0.01),
      and individuals reported more partners in the last six months than those not part
      of this dual risk (11.6 versus 8.2, P=0.02). In multivariate analyses, Tel-Aviv
      residency, lower education, performing receptive RUAI, misperception of HIV
      transmission and limited negotiation skills were positively associated with this
      dual-risk behaviour.

PMID- 18824625
TI  - Focus-on-Teens, sexual risk-reduction intervention for high-school adolescents:
      impact on knowledge, change of risk-behaviours, and prevalence of sexually
      transmitted diseases.
AB  - A community-based intervention, Focus-on-Kids (FOK) has demonstrated risk
      behaviour reduction of urban youth. We modified FOK to Focus-on-Teens (FOT) for
      high schools. High school adolescents (n=1190) were enrolled over successive
      school semesters. The small-group sessions were presented during the school-lunch
      hours. Confidential surveys were conducted at baseline, immediate, six-, and 12
      month postintervention for demographics, parental communication/monitoring,
      sexual risk behaviours and sexually transmitted diseases (STDs)/HIV/condom-usage
      knowledge. Sexually active participants were encouraged to volunteer for urine
      based STDs testing at the School-Based Health Centres. Many (47.4%) students
      reported having had sexual intercourse at baseline. Overall behaviours changed
      towards 'safer' sex behaviours (intent-to-use and using condoms, communicating
      with partner/parents about sex/condoms/STDs) with time (P<0.05). Proportion of
      students with complete correct knowledge of STDs/HIV increased to 88% at time 4
      from 80% at baseline after adjusting for age, gender and sexual activity
      (P<0.05). High prevalence of STDs was detected in 875 participants who reported
      for urine testing at time 1: trichomonas, 11.8%; chlamydia, 10.1% and gonorrhoea,
      4.1%. Prevalence decreased significantly for 310 participants who re-tested;
      chlamydia: 27.4% to 6.1% and gonorrhoea: 11.3% to 3.2%. FOT was successfully
      implemented as an STDs/HIV risk-reduction intervention. Sustained improvements of
      knowledge about STDs/HIV/condom usage, decreases in sexual risk behaviours
      supported the effectiveness of this intervention.

PMID- 18824626
TI  - Tackling STI epidemics through the HIV clinic: is sex high enough on the agenda?
AB  - Sexually transmitted infection (STI) rates among men having sex with men continue
      to increase. HIV services may operate independently to genitourinary medicine
      clinics and the sexual health of HIV-positive patients may be of low priority in
      the context of medical problems related to HIV. A prospective study of HIV
      positive gay men was conducted in a London outpatient clinic over a three-month
      period. Data were available for 90 men. Forty-five percent had STI screens in the
      preceding six months. These revealed a high rate of infections; 26 infections
      diagnosed in 14 men in the study period. Fifty-seven percent of the 90 men in the
      study had more than one partner in the past three months and approximately one
      third had unprotected sexual activity. A significant proportion of men were
      unaware of recent outbreaks of hepatitis C and lymphogranuloma venereum and of
      HIV postexposure prophylaxis. We therefore recommend that sexual history-taking,
      STI screens and health promotion should become a routine feature of HIV
      outpatient consultations in this group.

PMID- 18824627
TI  - Integrated community-based sexual health services for young people in urban
      areas: are we meeting the needs of the local community?
AB  - Community-based sexual health services (SHS) are intended to improve access for
      people who may have difficulty attending traditional genitourinary medicine
      clinics. The objective of this study was to review uptake of sexually transmitted
      infection (STI) testing in an outreach clinic for those under 25 in an area where
      Black and minority ethnic groups comprise the majority of the local population. A
      retrospective case-notes review was undertaken of those attending. Standards were
      that Fraser guidelines should be completed in all under 16-year-old and all
      clients should be offered STI testing, HIV testing and contraception (if
      applicable) in accordance with local standards. One hundred and seventeen clients
      attended. Ten percent self-reported ethnicity was Asian. Thirty-six (31%) clients
      tested for chlamydia. Thirty (26%) had an HIV test. Five (14% of those tested)
      had a positive nucleic acid amplification test for chlamydia. Five (13%) of those
      requesting long term contraception had STI testing. This service has successfully
      improved access to STI screening. However, there may have been missed
      opportunities to offer tests in those requesting contraception. Under
      representation of those of non-white ethnicity suggests access to SHS may be a
      particular problem and further work is required to improve the sexual health of
      the local community.

PMID- 18824628
TI  - Topical cidofovir for severe warts in a patient affected by AIDS and Hodgkin's
      lymphoma.
AB  - We describe a 42-year-old man with AIDS and Hodgkin's lymphoma whose severe and
      recalcitrant cutaneous warts resolved following treatment with local 1%
      cidofovir. Clinically significant improvements were observed in a two-week period
      of therapy. In advanced HIV disease complicated by additional haematological
      malignancy, cutaneous warts may be difficult to treat and present a challenge for
      the attending physicians. In similar clinical condition topical anti-human
      papillomavirus therapy may prove to be safe and curative.

PMID- 18824629
TI  - Cholangiocarcinoma presenting in an adolescent with vertically acquired HIV
      infection.
AB  - An adolescent with long-standing HIV infection who was severely immunosuppressed
      during HIV diagnosis developed cholangiocarcinoma 1.5 years after starting
      antiretroviral therapy.

PMID- 18824630
TI  - Two for the price of one.
AB  - This case is about an HIV seropositive young woman referred for the treatment of
      severe menorrhagia causing anaemia due to adenomyosis where the levonorgestrel
      releasing intrauterine system (Mirena) proved useful in treating her heavy
      periods and also provided effective contraception without interference from the
      liver enzyme-inducing effects of antiretroviral medications.

PMID- 18824631
TI  - Syphilis causing hearing loss.
AB  - An HIV-positive man with hepatitis B co-infection, naive to highly active
      antiretroviral therapy, with a CD4 of 594 copies/mL and HIV-1 viral load of
      140,070 copies, presented with right-sided facial weakness and hearing loss. He
      had been treated for secondary syphilis three months earlier when his rapid
      plasma reagin (RPR) result was 1:16, this had fallen to neat. At presentation,
      his RPR had risen to 1:16 again. A magnetic resonance imaging scan showed
      enhancement of the internal auditory canal and right cochlea. His cerebrospinal
      fluid examination was normal. He was treated with acyclovir and prednisolone
      before the syphilis serology was known. He was then treated for syphilis with
      doxycycline. He made an excellent recovery.

PMID- 18824632
TI  - Immunolocalization of aquaporin 1, 5, and 9 in the female pig reproductive
      system.
AB  - Thirteen mammalian aquaporin (AQP) isoforms have been identified, and they have a
      unique tissue-specific pattern of expression. AQPs have been documented in the
      reproductive system of both male and female humans, rats, and mice. However,
      tissue expression and cellular and subcellular localization of AQPs are unknown
      in the female reproductive system of pigs. In this study, AQP1 immunoreactivity
      was detected in the capillary endothelium of the ovary. Distinct immunolabeling
      of capillary endothelium was also observed in the oviduct and uterus. AQP5 was
      expressed in flattened follicle cells of primordial follicles, granulosa cells of
      developing ovarian follicles, and muscle cells of the oviduct and uterus.
      Staining of AQP5 was also observed in the epithelial cells of the oviduct and
      uterine epithelium. AQP9 immunoreactivity was observed in granulosa cells of
      developing follicles. AQP9 was also localized in the luminal epithelial cells of
      the oviduct and uterine epithelia cells. This is, to our knowledge, the first
      study that shows tissue expression and cellular and subcellular localization of
      AQPs in the reproductive system of the female pig. Moreover, these results
      suggest that several subtypes of the AQPs (AQP1, 5, and 9) are involved in
      regulation of water homeostasis in the reproductive system of gilts.

PMID- 18824633
TI  - Ultrastructural localization of integrin subunits beta4 and alpha3 within the
      migrating epithelial tongue of in vivo human wounds.
AB  - Subsequent to wounding, keratinocytes must quickly restore barrier function. In
      vitro wound models have served to elucidate mechanisms of epithelial closure and
      key roles for integrins alpha6beta4 and alpha3beta1. To extrapolate in vitro data
      to in vivo human tissues, we used ultrathin cryomicrotomy to simultaneously
      observe tissue ultrastructure and immunogold localization in unwounded skin and
      acute human cutaneous wounds. Localization of the beta4 integrin subunit in
      unwounded skin shows dominant hemidesmosomal association and minor basal
      keratinocyte lateral filopodic cell-cell expression. After wounding, beta4
      dominantly localized to cytokeratin-rich regions (trailing edge hemidesmosomes)
      and minor association with lamellipodia (leading edge). beta4 colocalizes with
      alpha3 within filopodia juxtaposed to wound matrix, and increased concentrations
      of beta4 were found in cytoplasmic vesicles within basal keratinocytes of the
      migrating tongue. alpha3 integrin subunit dominantly localized to filopodia
      within basal keratinocyte lateral cell-cell interfaces in unwounded skin and both
      cell-cell and cell-matrix filopodic interactions in wounded skin. This study
      indicates that beta4 interacts with the extracellular environment through both
      stable and transient interactions and may be managed through a different
      endosomal trafficking pathway than alpha3. alpha3 integrin, despite its ability
      to respond to alternate ligands after wounding, does so through a single
      structure, the filopodia.

PMID- 18824634
TI  - Chondrocyte phenotype and ectopic ossification in collagenase-induced tendon
      degeneration.
AB  - We report chondrocyte phenotype and ectopic ossification in a collagenase-induced
      patellar tendon injury model. Collagenase or saline was injected intratendinously
      in one limb. The patella tendon was harvested for assessment at different times.
      There was an increase in cellularity, vascularity, and loss of matrix
      organization with time after collagenase injection. The tendon did not heal
      histologically until week 32. Ectopic mineralization as indicated by von Kossa
      staining started from week 8. Tendon calcification was mediated by endochondral
      ossification, as shown by expression of type X collagen. viva CT imaging and
      polarization microscopy showed characteristic bony porous structures and collagen
      fiber arrangement, respectively, in the calcific regions. Marrow-like cells and
      blood vessels were observed inside calcific deposits. Chondrocyte-like cells as
      indicated by morphology, expression of type II collagen, and sox 9 were seen
      around and embedded inside the calcific deposits. Fibroblast-like cells expressed
      type II collagen and sox 9 at earlier times, suggesting that erroneous
      differentiation of healing tendon fibroblasts may account for failed healing and
      ossification in collagenase-induced tendon degeneration. Because this animal
      model replicates key histopathological changes in calcific tendinopathy, it can
      be used as a model for the study of its pathogenesis at the patellar tendon.

PMID- 18824635
TI  - Hormone-sensitive lipase expression and IHC localization in the rat ovary,
      oviduct, and uterus.
AB  - Hormone-sensitive lipase (HSL) is a key regulator of cholesterol esters
      metabolism. The aim of this study was to determine HSL localization in rat female
      reproductive organs during the ovarian cycle by IHC methods. HSL was located in
      the ovarian epithelium. The granulosa cells and oocytes of primordial follicles
      were immunonegative. In mature follicles, HSL was found in oocytes and theca and
      granulosa cells. However, HSL expression in theca cells and oocytes decreased
      during follicular atresia. Luteal cells showed HSL staining in cytoplasm during
      proestrus and estrus, in the nucleus during metestrus, and in cytoplasm and the
      nucleus during diestrus. In the tubaric ampulla, HSL was located in the
      epithelial cells nuclei and in the cilia during proestrus and estrus but mainly
      in the nucleus during metestrus and diestrus. In the isthmus, cells showed HSL
      immunolabeling in the nucleus and cilia during proestrus, but only in the cilia
      during estrus, metestrus, and diestrus. In the uterus, HSL was found in the
      epithelial cells nuclei. HSL-immunoreactive bands at 84, 67, 54, and 43 kDa were
      found in rat female reproductive organs. HSL labeling in the nucleus of
      epithelial and germ cells suggests an as yet unknown function for this protein,
      probably related to oogenesis and cell proliferation.

PMID- 18824636
TI  - Differential diagnosis and treatment of wheezing and asthma in young children.

PMID- 18824637
TI  - Nebulization therapy for asthma: a practical guide for the busy pediatrician.

PMID- 18824638
TI  - Syndrome of inappropriate antidiuretic hormone secretion in an infant with
      respiratory syncytial virus bronchiolitis.

PMID- 18824639
TI  - Lactose deficiency in infants.

PMID- 18824640
TI  - Depression and coronary heart disease: recommendations for screening, referral,
      and treatment: a science advisory from the American Heart Association Prevention
      Committee of the Council on Cardiovascular Nursing, Council on Clinical
      Cardiology, Council on Epidemiology and Prevention, and Interdisciplinary Council
      on Quality of Care and Outcomes Research: endorsed by the American Psychiatric
      Association.
AB  - Depression is commonly present in patients with coronary heart disease (CHD) and
      is independently associated with increased cardiovascular morbidity and
      mortality. Screening tests for depressive symptoms should be applied to identify
      patients who may require further assessment and treatment. This multispecialty
      consensus document reviews the evidence linking depression with CHD and provides
      recommendations for healthcare providers for the assessment, referral, and
      treatment of depression.

PMID- 18824641
TI  - Milrinone use is associated with postoperative atrial fibrillation after cardiac
      surgery.
AB  - BACKGROUND: Postoperative atrial fibrillation (AF), a frequent complication after
      cardiac surgery, causes morbidity and prolongs hospitalization. Inotropic drugs
      are commonly used perioperatively to support ventricular function. This study
      tested the hypothesis that the use of inotropic drugs is associated with
      postoperative AF. METHODS AND RESULTS: We evaluated perioperative risk factors in
      232 patients who underwent elective cardiac surgery. All patients were in sinus
      rhythm at surgery. Sixty-seven patients (28.9%) developed AF a mean of 2.9+/-2.1
      days after surgery. Patients who developed AF stayed in the hospital longer
      (P<0.001) and were more likely to die (P=0.02). Milrinone use was associated with
      an increased risk of postoperative AF (58.2% versus 26.1% in nonusers; P<0.001).
      Older age (63.4+/-10.7 versus 56.7+/-12.3 years; P<0.001), hypertension (P=0.04),
      lower preoperative ejection fraction (P=0.03), mitral valve surgery (P=0.02),
      right ventricular dysfunction (P=0.03), and higher mean pulmonary artery pressure
      (27.1+/-9.3 versus 21.8+/-7.5 mm Hg; P=0.001) also were associated with
      postoperative AF. In multivariable logistic regression, age (P<0.001), ejection
      fraction (P=0.02), and milrinone use (odds ratio, 4.86; 95% confidence interval,
      2.31 to 10.25; P<0.001) independently predicted postoperative AF. When only data
      from patients with pulmonary artery catheters were analyzed and pulmonary artery
      pressure was included in the model, age, milrinone use (odds ratio, 4.45; 95%
      confidence interval, 2.01 to 9.84; P<0.001), and higher pulmonary artery pressure
      (P=0.02) were associated with an increased risk of postoperative AF. Adding other
      potential confounders or stratifying analysis by mitral valve surgery did not
      change the association of milrinone use with postoperative AF. CONCLUSIONS:
      Milrinone use is an independent risk factor for postoperative AF after elective
      cardiac surgery.

PMID- 18824642
TI  - Hereditary deficiency of protein C or protein S confers increased risk of
      arterial thromboembolic events at a young age: results from a large family cohort
      study.
AB  - BACKGROUND: Whether hereditary protein S, protein C, or antithrombin deficiency
      is associated with arterial thromboembolism (ATE) and whether history of venous
      thromboembolism in these subjects predisposes them to subsequent ATE have yet to
      be determined. METHODS AND RESULTS: On the basis of pedigree analysis, we
      enrolled a total of 552 subjects (52% women; mean age, 46+/-17 years), belonging
      to 84 different kindreds, in this retrospective family cohort study. Detailed
      information on previous episodes of venous thromboembolism, ATE, anticoagulant
      use, and atherosclerosis risk factors was collected. Primary study outcome was
      objectively verified symptomatic ATE. Of 552 subjects, 308 had protein S (35%),
      protein C (39%), or antithrombin (26%) deficiency. Overall, annual incidences of
      ATE were 0.34% (95% confidence interval [CI], 0.23 to 0.49) in deficient versus
      0.17% (95% CI, 0.09 to 0.28) in nondeficient subjects; the hazard ratio was 2.3
      (95% CI, 1.2 to 4.5). Because the risk hazards varied over lifetime, we performed
      a time-dependent analysis. After adjusting for atherosclerosis risk factors and
      clustering within families, we found that deficient subjects had a 4.7-fold (95%
      CI, 1.5 to 14.2; P=0.007) higher risk for ATE before 55 years of age versus 1.1
      (95% CI, 0.5 to 2.6) thereafter compared with nondeficient family members. For
      separate deficiencies, the risks were 4.6- (95% CI, 1.1 to 18.3), 6.9- (95% CI,
      2.1 to 22.2), and 1.1- (95% CI, 0.1 to 10.9) fold higher in protein S-, protein C
      , and antithrombin-deficient subjects, respectively, before 55 years of age.
      History of venous thromboembolism was not related to subsequent ATE (hazard
      ratio, 1.1; 95% CI, 0.5 to 2.2). CONCLUSIONS: Compared with nondeficient family
      members, subjects with protein S or protein C deficiency but not antithrombin
      deficiency have a higher risk for ATE before 55 years of age that is independent
      of prior venous thromboembolism.

PMID- 18824643
TI  - Serum potassium and clinical outcomes in the Eplerenone Post-Acute Myocardial
      Infarction Heart Failure Efficacy and Survival Study (EPHESUS).
AB  - BACKGROUND: Aldosterone blockade is recommended for patients with congestive
      heart failure after acute myocardial infarction complicated by left ventricular
      systolic dysfunction; however, the perceived risk of hyperkalemia may limit
      implementation of this therapeutic approach. This subanalysis examined the
      relationship between eplerenone, serum potassium (K(+)), and clinical outcomes in
      the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and
      Survival Study (EPHESUS). METHODS AND RESULTS: Hospitalized patients with
      congestive heart failure after acute myocardial infarction complicated by left
      ventricular systolic dysfunction (left ventricular ejection fraction < or =40%)
      treated with standard therapy were randomized 3 to 14 days after the acute
      myocardial infarction to additional treatment with eplerenone (25 to 50 mg/d;
      n=3319) or placebo (n=3313). Patients were excluded if baseline K(+) was >5.0
      mEq/L or serum creatinine was >2.5 mg/dL. In patients receiving standard therapy,
      the addition of eplerenone resulted in a 4.4% absolute increase in the incidence
      of K(+) >5.5 mEq/L, a 1.6% increase of K(+) > or =6.0 mEq/L, and a 4.7% absolute
      decrease in hypokalemia (K(+) <3.5 mEq/L). Four independent baseline predictors
      of hyperkalemia (defined as > or =6.0 mEq/L) were identified: potassium (K(+)
      greater than the median; 4.3 mEq/L), estimated glomerular filtration rate (< or
      =60 mL . min(-1) . 1.73 m(-2)), history of diabetes mellitus, and prior use of
      antiarrhythmic agents. None of these independent baseline risk factors
      significantly impacted the cardiovascular benefit of eplerenone for reducing all
      cause mortality. CONCLUSIONS: Use of selective aldosterone blockade with
      eplerenone within the dose range of 25 to 50 mg/d in post-acute myocardial
      infarction patients with heart failure and left ventricular systolic dysfunction
      who are treated with standard therapy improves outcomes without an excess of risk
      of hyperkalemia (> or =6.0 mEq/L) when periodic monitoring of serum K(+) is
      instituted.

PMID- 18824644
TI  - Atrial fibrillation after isolated coronary surgery affects late survival.
AB  - BACKGROUND: Atrial fibrillation (AF) after coronary artery bypass graft surgery
      is a difficult problem and a continuing source of morbidity and mortality.
      However, the prognostic implications of postoperative AF are still in dispute.
      Our aim was to ascertain the impact of AF after coronary artery bypass graft on
      postoperative survival and to assess its prognostic role in cause-specific
      mortality. METHODS AND RESULTS: We conducted a prospective observational study of
      1832 patients undergoing isolated coronary artery bypass graft between January
      2000 and December 2005 at 2 cardiac surgery centers in northern Italy. Patients
      affected by postoperative AF were identified and followed up until death or study
      end (April 30, 2007). A total of 570 patients (31%) developed AF after coronary
      surgery. Patients affected by postoperative AF experienced a longer hospital stay
      (7 days [25th to 75th percentile, 7 to 10 days] versus 7 days [25th to 75th
      percentile, 6 to 8 days]; P<0.001). Hospital mortality also was higher in AF
      patients (3.3% versus 0.5%; P<0.001). On discharge, 1806 patients were alive; 143
      were lost to follow-up. The remaining 1663 were followed up for a median of 51
      months (25th to 75th percentile, 41 to 63 months); 126 of them died after a
      median of 14 months (25th to 75th percentile, 5 to 32 months). Long-term
      mortality rates were significantly higher for patients with postoperative AF
      (2.99 per 100 person-years; 95% confidence interval, 2.33 to 3.84; 61 deaths)
      compared with those without the arrhythmia (1.34 per 100 person-years; 95%
      confidence interval, 1.05 to 1.71; 65 deaths), with an adjusted hazard ratio of
      2.13 (P<0.001) and 2.56 (P=0.001) when also accounting for the prescription of
      warfarin at discharge. With Cox regression, patients with AF were shown to be at
      higher risk of dying from embolism (adjusted hazard ratio, 4.33; 95% confidence
      interval, 1.78 to 10.52) but not from other causes. CONCLUSIONS: Postoperative AF
      affects early and late mortality after isolated coronary artery bypass graft
      surgery. Patients affected by AF are at higher risk of fatal embolic events.
      Careful postoperative surveillance with a specific antiarrhythmic and
      antithrombotic prophylaxis, aimed at reducing AF and its complications, is
      recommended.

PMID- 18824645
TI  - Does obesity modify the effect of blood pressure on the risk of cardiovascular
      disease? A population-based cohort study of more than one million Swedish men.
AB  - BACKGROUND: Some studies have suggested that increased blood pressure has a
      stronger effect on the risk of cardiovascular disease (CVD) in lean persons than
      in obese persons, although this is not a universal finding. Given the
      inconsistency of this result, we tested it using a large population-based cohort
      data set. METHODS AND RESULTS: Systolic and diastolic blood pressures (BPs) and
      body mass index were measured in 1 145 758 Swedish men born between 1951 and 1976
      who were in young adulthood (median age 18.2 years). During the register-based
      follow-up, which lasted until the end of 2006, 65 611 new CVD events took place,
      including 6799 myocardial infarctions and 8827 strokes. Hazard ratios (HRs) per 1
      SD increase in systolic and diastolic BP were computed within established body
      mass index categories (underweight, normal, overweight, or obese) with Cox
      proportional hazards models. The strongest associations of diastolic BP with CVD
      (HR 1.18), myocardial infarction (HR 1.22), and stroke (HR 1.13) were observed in
      the obese category. For systolic BP, the strongest associations were observed in
      the obese category with CVD (HR 1.16) and stroke (HR 1.29) but in the overweight
      category with myocardial infarction (HR 1.19). We observed statistically
      significant interactions (P<0.0001) with body mass index for diastolic BP in
      relation to CVD and for systolic BP in relation to CVD and stroke. CONCLUSIONS:
      In contrast to the findings of previous studies, we observed a general increase
      in the magnitude of the association between blood pressure and subsequent CVD
      with increasing body mass index. Hypertension should not be regarded as a less
      serious risk factor in obese than in lean or normal-weight persons.

PMID- 18824646
TI  - Functionally opposing roles of extracellular signal-regulated kinase 1/2 and p38
      mitogen-activated protein kinase in the regulation of cardiac contractility.
AB  - BACKGROUND: Extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 mitogen
      activated protein kinase (p38-MAPK) have been shown to regulate various cellular
      processes, including cell growth, proliferation, and apoptosis in the heart.
      However, the function of these signaling pathways in the control of cardiac
      contractility is unclear. Here, we characterized the contribution of ERK1/2 and
      p38-MAPK to the inotropic effect of endothelin-1 (ET-1). METHODS AND RESULTS: In
      isolated perfused rat hearts, infusion of ET-1 (1 nmol/L) for 10 minutes
      increased contractility and phosphorylation of ERK1/2 and their downstream target
      p90 ribosomal S6 kinase (p90RSK). Suppression of ERK1/2 activation prevented
      p90RSK phosphorylation and attenuated the inotropic effect of ET-1.
      Pharmacological inhibition of epidermal growth factor receptor kinase activity
      abolished ET-1-induced epidermal growth factor receptor transactivation and
      ERK1/2 and p90RSK phosphorylation and reduced ET-1-mediated inotropic response.
      Moreover, inhibition of the p90RSK target Na(+)-H(+) exchanger 1 attenuated the
      inotropic effect of ET-1. In contrast to ERK1/2 signaling, suppression of p38
      MAPK activity further augmented ET-1-enhanced contractility, which was
      accompanied by increased phosphorylation of phospholamban at Ser-16. CONCLUSIONS:
      MAPKs play opposing roles in the regulation of cardiac contractility in that the
      ERK1/2-mediated positive inotropic response to ET-1 is counterbalanced by
      simultaneous activation of p38-MAPK. Hence, selective activation of ERK1/2
      signaling and inhibition of p38-MAPK signaling may represent novel means to
      support cardiac function in disease.

PMID- 18824647
TI  - Cardiology patient pages. Aortic dissection.

PMID- 18824648
TI  - Pericarditis heralding Erdheim-Chester disease.

PMID- 18824649
TI  - Heartbreaking case of acetaminophen poisoning.

PMID- 18824650
TI  - Letter by Boriani et al regarding article, "Death without prior appropriate
      implantable cardioverter-defibrillator therapy: a competing risk study".

PMID- 18824652
TI  - Migraine: a matter of the heart?

PMID- 18824653
TI  - A novel role for tissue-type plasminogen activator: prevention of thromboembolic
      occlusion.

PMID- 18824654
TI  - The "sunshine deficit" and cardiovascular disease.

PMID- 18824655
TI  - Emerging concepts and translational priorities in pulmonary arterial
      hypertension.

PMID- 18824656
TI  - Thoracopagus conjoined twins.

PMID- 18824657
TI  - Prevalence and risk factors of masked hypertension identified by multiple self
      blood pressure measurement.

PMID- 18824658
TI  - Spironolactone attenuates oxidative stress in patients with chronic kidney
      disease.

PMID- 18824659
TI  - Maternal and uteroplacental hemodynamics for the classification and prediction of
      preeclampsia.

PMID- 18824660
TI  - Early and late preeclampsia: two different maternal hemodynamic states in the
      latent phase of the disease.
AB  - Because early and late preeclampsia (PE) are thought to be different disease
      entities, we compared maternal cardiac function at 24 weeks gestation in a group
      of normotensive asymptomatic patients with subsequent development of early (<34
      weeks gestation) and late (>or=34 weeks gestation) PE (blood pressure
      >140/90+proteinuria >300 mg/dL) to detect possible early differences in the
      hemodynamic state. A group of 1345 nulliparous normotensive asymptomatic women
      underwent at 24 weeks gestation uterine artery Doppler evaluation and maternal
      echocardiography calculating total vascular resistance. In the subsequent follow
      up 107 patients showed PE: 32 patients had late and 75 had early PE. Five of 32
      patients with late PE and 45 of 75 patients with early PE had bilateral notching
      of the uterine artery at 24 weeks (15.6% versus 60.0%; P<0.05). Total vascular
      resistance was 1605+/-248 versus 739+/-244 dyn . s . cm(-5), and cardiac output
      was 4.49+/-1.09 versus 8.96+/-1.83 L in early versus late PE (P<0.001).
      Prepregnancy body mass index was higher in late versus early PE (28+/-6 versus
      24+/-2 kg/m(2); P<0.001). Early and late PE appear to develop from different
      hemodynamic states. Late PE appears to be more frequent in patients with high
      body mass index and low total vascular resistance; earlier forms of PE appear to
      be more frequent in patients with lower BMI and with bilateral notching of the
      uterine artery. These findings support the hypothesis of different hemodynamics
      and origins for early PE (placental mediated, linked to defective trophoblast
      invasion with high percentage of altered uterine artery Doppler) and late PE
      (linked to constitutional factors such as high body mass index).

PMID- 18824661
TI  - Vitamin D and hypertension: does the women's health initiative solve the
      question?

PMID- 18824663
TI  - Interaction among heme oxygenase, nuclear factor-kappaB, and transcription
      activating factors in cardiac hypertrophy in hypertension.
AB  - Deoxycorticosterone acetate-induced hypertension is a volume overload and human
      primary aldosteronism model characterized by severe cardiac lesions attributed to
      elevated inflammation, oxidative stress, fibrosis, and hypertrophy. An important
      cytoprotective pathway that counteracts tissue insults is the heme oxygenase (HO)
      system. Although the HO-1 gene promoter contains consensus binding sites for
      proinflammatory/oxidative transcription factors like nuclear factor-kappaB,
      activating protein (AP)-1, and AP-2, the effects of HO inducers on these
      transcription factors in cardiac lesions of deoxycorticosterone acetate
      hypertension are not fully understood. Hemin therapy normalized systolic blood
      pressure and markedly reduced the left:right ventricular ratio, left ventricular
      wall thickness, and left ventricle:body weight ratio, whereas the HO blocker,
      chromium mesoporphyrin, exacerbated cardiac fibrosis/hypertrophy in
      deoxycorticosterone acetate-hypertensive rats. The cardioprotection by hemin was
      accompanied by increased HO-1, HO activity, cGMP, superoxide dismutase, catalase,
      the total antioxidant capacity alongside the reduction of 8-isoprostane, AP-1, AP
      2, nuclear factor-kappaB, and c-Jun-NH(2)-terminal kinase, whereas chromium
      mesoporphyrin abolished the hemin effects. Furthermore, hemin therapy attenuated
      transforming growth factor-beta(1) and extracellular matrix proteins like
      fibronectin and collagen, with a corresponding reduction of histopathologic
      lesions, including longitudinal/cross-sectional muscle fiber thickness, scarring,
      muscular hypertrophy, coronary arteriolar thickening, and collagen deposition.
      The suppression of AP-1, AP-2, nuclear factor-kappaB, and c-Jun-NH(2)-terminal
      kinase proinflammatory/oxidative mediators in the left ventricle of hemin-treated
      animals is a novel observation that may account for cardioprotection in
      deoxycorticosterone acetate hypertension. By concomitantly upregulating HO
      activity and cGMP and potentiating the total antioxidant status, hemin therapy
      reduced hypertension, suppressed oxidative stress, and attenuated extracellular
      matrix and remodeling proteins, with a reduction of histopathologic lesions that
      characterize cardiac fibrosis, hypertrophy, and end-stage organ damage.

PMID- 18824662
TI  - Effect of calcium and vitamin D supplementation on blood pressure: the Women's
      Health Initiative Randomized Trial.
AB  - Experimental and epidemiological studies suggest that calcium and vitamin D
      supplements may lower blood pressure. We examined the effect of calcium plus
      vitamin D supplementation on blood pressure and the incidence of hypertension in
      postmenopausal women. The Women's Health Initiative Calcium/Vitamin D Trial
      randomly assigned 36 282 postmenopausal women to receive 1000 mg of elemental
      calcium plus 400 IU of vitamin D3 daily or placebo in a double-blind fashion.
      Change in blood pressure and the incidence of hypertension were ascertained. Over
      a median follow-up time of 7 years, there was no significant difference in the
      mean change over time in systolic blood pressure (0.22 mm Hg; 95% CI: -0.05 to
      0.49 mm Hg) and diastolic blood pressure (0.11 mm Hg; 95% CI: -0.04 to 0.27 mm
      Hg) between the active and placebo treatment groups. This null result was robust
      in analyses accounting for nonadherence to study pills and in baseline subgroups
      of interest, including black subjects and women with hypertension or high levels
      of blood pressure, with low intakes of calcium and vitamin D or low serum levels
      of vitamin D. In 17 122 nonhypertensive participants at baseline, the hazard
      ratio for incident hypertension associated with calcium/vitamin D treatment was
      1.01 (95% CI: 0.96 to 1.06.) In postmenopausal women, calcium plus vitamin D3
      supplementation did not reduce either blood pressure or the risk of developing
      hypertension over 7 years of follow-up.

PMID- 18824664
TI  - Nitric oxide upregulates dimethylarginine dimethylaminohydrolase-2 via cyclic GMP
      induction in endothelial cells.
AB  - Dimethylarginine dimethylaminohydrolase (DDAH) is an enzyme that metabolizes
      asymmetrical N(G),N(G)-dimethyl-L-arginine (ADMA) and N(G)-monomethyl-L-arginine
      (MMA), which are competitive endogenous inhibitors of NO synthase. However, it
      remains unknown whether NO itself influences DDAH activity and/or ADMA/MMA
      contents to regulate NO generation via a biofeedback mechanism. The present study
      was designed to examine the effects of NO on intracellular ADMA and MMA contents
      and DDAH gene expression levels and enzymatic activities in cultured rat aortic
      endothelial cells. The NO donors SNAP and NOR3 did not influence DDAH-1
      expression but increased DDAH-2 mRNA and protein levels in concentration
      dependent manners. SNAP upregulated DDAH enzymatic activity and reduced the MMA
      and ADMA contents but did not affect the symmetrical N(G),N'(G)-dimethyl-L
      arginine and L-arginine levels, thereby negating a mediatory role for system y(+)
      in ADMA/MMA downregulation. The cGMP agonists 8-bromo-cGMP and C-type natriuretic
      peptide also stimulated DDAH-2 gene and protein expression levels and DDAH
      activity and increased the amount of nitrite/nitrate released into the culture
      supernatants. SNAP-induced DDAH-2 gene expression and DDAH activity were
      significantly inhibited by a protein kinase G inhibitor, KT5823, and a soluble
      guanylate cyclase inhibitor, ODQ, suggesting a mediatory role for cGMP in NO
      induced DDAH-2 expression. Suppression of DDAH-2 mRNA using small interfering RNA
      technology abrogated NO-induced DDAH-2 expression. These data demonstrate that NO
      acts on endothelial cells to induce DDAH-2 expression via a cGMP-mediated process
      to reduce ADMA/MMA. Thus, the DDAH-2-ADMA/MMA-endothelial NO synthase regulatory
      pathway and NO-induced cGMP constitute a positive feedback loop that ultimately
      serves to maintain NO levels in the endothelial environment.

PMID- 18824665
TI  - Microsomal prostaglandin synthase-1-derived prostaglandin E2 protects against
      angiotensin II-induced hypertension via inhibition of oxidative stress.
AB  - Prostaglandin (PG) E(2) has an established role in the regulation of vascular
      tone and reactivity. The present study examined the role and mechanism of
      microsomal PG synthase-1 (mPGES-1) in vascular response to angiotensin II (Ang
      II) infusion. A 7-day Ang II infusion at 0.35 mg/kg per day via osmotic minipump
      had no obvious effect on mean arterial blood pressure in mPGES-1(+/+) mice but
      induced a marked hypertensive response in mPGES-1(-/-) mice, associated with a
      parallel increase in urinary 8-isoprostane excretion and aortic NADPH oxidase
      activity and mRNA expression of p47(phox), gp91(phox), and Nox1. The hypertension
      in mPGES-1(-/-) mice was completely prevented by Tempol treatment and was fully
      restored on termination of the antioxidant. Apocynin induced a similar blood
      pressure-lowering effect as Tempol. The Ang II infusion induced mRNA expression
      of mPGES-1, as well as mPGES-2 and cytosolic PGE synthase in the aortas as
      assessed by real-time RT-PCR. Immunohistochemistry revealed remarkably enhanced
      immunoreactivity of mPGES-1 mostly in vascular smooth muscle cells. In cultured
      vascular smooth muscle cells, Ang II exerted a direct stimulatory effect on
      reactive oxygen species production, NADPH oxidase activity, and expression of
      p47(phox), gp91(phox), and Nox1 that were all inhibited by PGE(2). The -/- mice
      also exhibited enhanced renal hemodynamic response to acute Ang II infusion at
      150 nmol/kg per minute via a jugular vein over a period of 40 minutes. These
      results suggest that mPGES-1-derived PGE(2) buffers Ang II-induced
      vasoconstriction via inhibition of NADPH oxidase-dependent reactive oxygen
      species production.

PMID- 18824666
TI  - Teaching Video NeuroImage: near complete ophthalmoplegia in GQ1b antibody
      positive Miller Fisher: video and MRI correlation.

PMID- 18824667
TI  - Patient page. Epilepsy and pregnancy: are seizure medications safe?

PMID- 18824669
TI  - Go to the head of the class to avoid vascular dementia and skip diabetes and
      obesity.

PMID- 18824670
TI  - Vive la difference! On potential sex differences in response to thrombolysis.

PMID- 18824671
TI  - Serum cystatin C and the risk of Alzheimer disease in elderly men.
AB  - BACKGROUND: Multiple lines of research suggest that increased cystatin C activity
      in the brain protects against the development of Alzheimer disease (AD). METHODS:
      Serum cystatin C levels were analyzed at two examinations of the Uppsala
      Longitudinal Study of Adult Men, a longitudinal, community-based study of elderly
      men (age 70 years, n = 1,153 and age 77 years, n = 761, a subset of the age 70
      examination). Cox regressions were used to examine associations between serum
      cystatin C and incident AD. AD cases were identified by cognitive screening and
      comprehensive medical chart review in all subjects. RESULTS: On follow-up (median
      11.3 years), 82 subjects developed AD. At age 70 years, lower cystatin C was
      associated with higher risk of AD independently of age, APOE4 genotype,
      glomerular filtration rate, diabetes, hypertension, stroke, cholesterol, body
      mass index, smoking, education level, and plasma amyloid-beta protein 40 and 42
      levels (hazard ratio [HR] for lowest [<1.12 micromol/L] vs highest [>1.30
      micromol/L] tertile = 2.67, 95% CI 1.22-5.83, p < 0.02). The results were similar
      at age 77 years (43 participants developed AD during follow-up). Furthermore, a
      0.1-mumol/L decrease of cystatin C between ages 70 and 77 years was associated
      with a 29% higher risk of incident AD (HR 1.29, 95% CI 1.03-1.63, p < 0.03).
      CONCLUSIONS: Low levels of serum cystatin C precede clinically manifest Alzheimer
      disease (AD) in elderly men free of dementia at baseline and may be a marker of
      future risk of AD. These findings strengthen the evidence for a role for cystatin
      C in the development of clinical AD.

PMID- 18824672
TI  - Warfarin use leads to larger intracerebral hematomas.
AB  - BACKGROUND: Among patients with intracerebral hemorrhage (ICH), warfarin use
      before onset leads to greater mortality. In a retrospective study, we sought to
      determine whether warfarin use is associated with larger initial hematoma volume,
      one determinant of mortality after ICH. METHODS: We identified all patients
      hospitalized with ICH in the Greater Cincinnati region from January through
      December 2005. ICH volumes were measured on the first available brain scan by
      using the abc/2 method. Univariable analyses and a multivariable generalized
      linear model were used to determine whether international normalized ratio (INR)
      influenced initial ICH volume after adjusting for other factors, including age,
      race, sex, antiplatelet use, hemorrhage location, and time from stroke onset to
      scan. RESULTS: There were 258 patients with ICH, including 51 patients taking
      warfarin. In univariable comparison, when INR was stratified, there was a trend
      toward a difference in hematoma volume by INR category (INR <1.2, 13.4 mL; INR
      1.2-2.0, 9.3 mL; INR 2.1-3.0, 14.0 mL; INR >3.0, 33.2 mL; p = 0.10). In the
      model, compared with patients with INR <1.2, there was no difference in hematoma
      size for patients with INR 1.2-2.0 (p = 0.25) or INR 2.1-3.0 (p = 0.36), but
      patients with INR >3.0 had greater hematoma volume (p = 0.02). Other predictors
      of larger hematoma size were ICH location (lobar compared with deep cerebral, p =
      0.02) and shorter time from stroke onset to scan (p < 0.001). CONCLUSION:
      Warfarin use was associated with larger initial intracerebral hemorrhage (ICH)
      volume, but this effect was only observed for INR values >3.0. Larger ICH volume
      among warfarin users likely accounts for part of the excess mortality in this
      group.

PMID- 18824673
TI  - Vanishing MS T2-bright lesions before puberty: a distinct MRI phenotype?
AB  - BACKGROUND: Multiple sclerosis (MS) onset before puberty may have a distinct
      clinical presentation. Pediatric patients with MS may less often meet MRI
      diagnostic criteria for adults. Whether initial MRI presentation is distinct in
      prepubertal patients is unknown. METHODS: We queried the UCSF MS database for
      pediatric patients with MS (onset <or=18 years) who underwent brain MRI within 3
      months of initial symptoms. The overall number of lesions and the number of well
      defined and ovoid, large, confluent, and gadolinium-enhancing lesions were
      compared between patients with earlier-onset (EOPMS) (<11 years) and later-onset
      (LOPMS) (>or=11 years) pediatric MS. The next available brain MRI scan was used
      to evaluate lesion resolution. RESULTS: Thirteen children with EOPMS (median age
      8.90 years, range [3.58-10.98], 38% girls) and 18 with LOPMS (median age 14.47
      years, range [11.78-18.00], 61% girls) were identified. While the overall number
      of T2-bright lesions was similar in the two groups, patients with EOPMS had fewer
      well-defined ovoid T2-bright lesions (median = 7, range [0-29] vs 21.5, [4-100];
      p = 0.004) and more often had confluent lesions (31% of patients vs 0%; p = 0.02)
      on their first MRI compared with patients with LOPMS. Ninety-two percent of
      patients with EOPMS had a reduction in the number of T2-bright lesions on the
      second scan compared to 29% of patients with LOPMS (p = 0.002). CONCLUSIONS: The
      distinct prepubertal multiple sclerosis (MS) MRI phenotype suggests that
      underlying biologic processes may differ in earlier-onset pediatric MS compared
      to later-onset pediatric MS. These findings may delay diagnosis in that age
      range. MRI criteria for MS diagnosis may need to be revised before puberty.

PMID- 18824674
TI  - Hippocampal and thalamic atrophy in mild temporal lobe epilepsy: a VBM study.
AB  - BACKGROUND: Patients with temporal lobe epilepsy (TLE) often have mild drug
      responsive epilepsy which is frequently associated with MRI detectable mesial
      temporal sclerosis (MTS), indicating that MTS is not necessarily related to
      seizure severity. To better define the anatomic substrates associated with TLE,
      we applied voxel-based morphometry (VBM) analysis to patients with mild TLE.
      METHODS: Optimized VBM was applied to the MRI brain images of 95 consecutive
      unrelated patients who were diagnosed with mild TLE and to 37 healthy controls.
      We complemented the investigation by calculating the gray matter volume of
      regions of interest (ROIs) in the bilateral hippocampus. Standard MRI scans
      revealed evidence of MTS (pTLE) in 34 patients, and no evidence of MTS in the
      remaining 61 (nTLE). RESULTS: The VBM analysis provided evidence of a reduction
      in gray matter volume in the hippocampus and thalami. The gray matter volume
      reduction in the thalamic and hippocampal networks was significantly more severe
      in patients with pTLE than in the nTLE or the control groups (at a threshold of
      FWE-corrected p < 0.05). Patients with nTLE showed the same gray matter
      abnormalities at an uncorrected statistical threshold (p < 0.001) compared to
      normal controls. ROI analysis confirmed the ipsilateral hippocampal atrophy that
      was detected in routine MRI scans. CONCLUSIONS: The structural abnormalities seen
      in patients with mild temporal lobe epilepsy (TLE) demonstrate that a temporo
      limbic pathway, which includes the thalamus, plays a major role in the
      pathogenesis of TLE. It is likely that other factors, especially genetic ones,
      play a major role in the causation and severity of TLE.

PMID- 18824675
TI  - Meningeal dissemination in primary CNS lymphoma: prospective evaluation of 282
      patients.
AB  - BACKGROUND: The impact of meningeal dissemination in primary CNS lymphoma (PCNSL)
      is debated, and the reported frequency varies. We prospectively evaluated the
      diagnostic value of PCR in comparison with CSF cytomorphology and MRI for
      diagnosing meningeal dissemination in PCNSL. METHODS: We evaluated 282 patients
      from a multicenter therapy study for PCNSL for the presence of meningeal
      dissemination: 205 with CSF cytomorphology, 171 with PCR of the rearranged
      immunoglobulin heavy-chain genes in CSF, and 217 with cranial MRI. RESULTS:
      Meningeal dissemination was found in 33 of 205 patients (16%) by cytomorphology,
      in 19 of 171 (11%) patients evaluated by PCR, and in 8 of 217 patients (4%) by
      MRI. Considering either of these methods, the relative frequency of meningeal
      dissemination was 17.4% (49 of 282 patients). PCR was monoclonal in 6 of 19 (32%)
      samples with positive cytomorphology, 1 of 13 samples (8%) with suspicious
      cytology, and in 10 of 105 (10%) cytologically negative samples. In 11 samples
      with positive and 12 with suspicious cytology, PCR showed only a polyclonal
      pattern. The probability of meningeal dissemination detection was higher in cases
      with CSF pleocytosis (>5/microL) with an OR of 2.48 (95% CI 1.15-5.34, p =
      0.018). CSF protein had no predictive value for meningeal dissemination
      detection. CONCLUSIONS: We found a low rate of meningeal dissemination in primary
      CNS lymphoma in this large prospective study. The rate of discordant PCR and
      cytomorphologic results was high. Thus, the methods should be regarded as
      complementary. CSF pleocytosis had predictive value for meningeal dissemination
      detection.

PMID- 18824676
TI  - Hypermanganesemia, hereditary hemorrhagic telangiectasia, brain abscess: the
      hepatic connection.

PMID- 18824677
TI  - In neurocysticercosis, CSF cytokines correlate with cerebral blood flow
      velocities.

PMID- 18824678
TI  - Multifocal neuropathy associated with West Nile virus infection.

PMID- 18824679
TI  - The NIH registry on use of the Wingspan stent for symptomatic 70-99% intracranial
      arterial stenosis.

PMID- 18824680
TI  - Variability of brain death determination guidelines in leading US neurologic
      institutions.

PMID- 18824681
TI  - Robust dynamic classes revealed by measuring the response function of a social
      system.
AB  - We study the relaxation response of a social system after endogenous and
      exogenous bursts of activity using the time series of daily views for nearly 5
      million videos on YouTube. We find that most activity can be described accurately
      as a Poisson process. However, we also find hundreds of thousands of examples in
      which a burst of activity is followed by an ubiquitous power-law relaxation
      governing the timing of views. We find that these relaxation exponents cluster
      into three distinct classes and allow for the classification of collective human
      dynamics. This is consistent with an epidemic model on a social network
      containing two ingredients: a power-law distribution of waiting times between
      cause and action and an epidemic cascade of actions becoming the cause of future
      actions. This model is a conceptual extension of the fluctuation-dissipation
      theorem to social systems [Ruelle, D (2004) Phys Today 57:48-53] and [Roehner BM,
      et al., (2004) Int J Mod Phys C 15:809-834], and provides a unique framework for
      the investigation of timing in complex systems.

PMID- 18824682
TI  - The "Cheshire Cat" escape strategy of the coccolithophore Emiliania huxleyi in
      response to viral infection.
AB  - The coccolithophore Emiliania huxleyi is one of the most successful eukaryotes in
      modern oceans. The two phases in its haplodiploid life cycle exhibit radically
      different phenotypes. The diploid calcified phase forms extensive blooms, which
      profoundly impact global biogeochemical equilibria. By contrast, the ecological
      role of the noncalcified haploid phase has been completely overlooked. Giant
      phycodnaviruses (Emiliania huxleyi viruses, EhVs) have been shown to infect and
      lyse diploid-phase cells and to be heavily implicated in the regulation of
      populations and the termination of blooms. Here, we demonstrate that the haploid
      phase of E. huxleyi is unrecognizable and therefore resistant to EhVs that kill
      the diploid phase. We further show that exposure of diploid E. huxleyi to EhVs
      induces transition to the haploid phase. Thus we have clearly demonstrated a
      drastic difference in viral susceptibility between life cycle stages with
      different ploidy levels in a unicellular eukaryote. Resistance of the haploid
      phase of E. huxleyi provides an escape mechanism that involves separation of
      meiosis from sexual fusion in time, thus ensuring that genes of dominant diploid
      clones are passed on to the next generation in a virus-free environment. These
      "Cheshire Cat" ecological dynamics release host evolution from pathogen pressure
      and thus can be seen as an opposite force to a classic "Red Queen" coevolutionary
      arms race. In E. huxleyi, this phenomenon can account for the fact that the
      selective balance is tilted toward the boom-and-bust scenario of optimization of
      both growth rates of calcifying E. huxleyi cells and infectivity of EhVs.

PMID- 18824683
TI  - Caulobacter requires a dedicated mechanism to initiate chromosome segregation.
AB  - Chromosome segregation in bacteria is rapid and directed, but the mechanisms
      responsible for this movement are still unclear. We show that Caulobacter
      crescentus makes use of and requires a dedicated mechanism to initiate chromosome
      segregation. Caulobacter has a single circular chromosome whose origin of
      replication is positioned at one cell pole. Upon initiation of replication, an 8
      kb region of the chromosome containing both the origin and parS moves rapidly to
      the opposite pole. This movement requires the highly conserved ParABS locus that
      is essential in Caulobacter. We use chromosomal inversions and in vivo time-lapse
      imaging to show that parS is the Caulobacter site of force exertion, independent
      of its position in the chromosome. When parS is moved farther from the origin,
      the cell waits for parS to be replicated before segregation can begin. Also, a
      mutation in the ATPase domain of ParA halts segregation without affecting
      replication initiation. Chromosome segregation in Caulobacter cannot occur unless
      a dedicated parS guiding mechanism initiates movement.

PMID- 18824684
TI  - Positioning of autoimmune TCR-Ob.2F3 and TCR-Ob.3D1 on the MBP85-99/HLA-DR2
      complex.
AB  - Since the first determination of structure of the HLA-A2 complex, >200
      MHC/peptide structures have been recorded, whereas the available T cell receptor
      (TCR)/peptide/MHC complex structures now are <20. Among these structures, only
      six are TCR/peptide/MHC Class II (MHCII) structures. The most recent of these
      structures, obtained by using TCR-Ob.1A12 from a multiple sclerosis patient and
      the MBP85-99/HLA-DR2 complex, was very unusual in that the TCR was located near
      the N-terminal end of the peptide-binding cleft of the MHCII protein and had an
      orthogonal angle on the peptide/MHC complex. The unusual structure suggested the
      possibility of a disturbance of its signaling capability that could be related to
      autoimmunity. Here, homology modeling and a new simulation method developed for
      TCR/peptide/MHC docking have been used to examine the positioning of the complex
      of two additional TCRs obtained from the same patient (TCR-Ob.2F3 or TCR-Ob.3D1
      with MBP85-99/HLA-DR2). The structures obtained by this simulation are compatible
      with available data on peptide specificity of the TCR epitope. All three TCRs
      from patient Ob including that from the previously determined crystal structure
      show a counterclockwise rotation. Two of them are located near the N terminus of
      the peptide-binding cleft, whereas the third is near the center. These data are
      compatible with the hypothesis that the rotation of the TCRs may alter the
      downstream signaling.

PMID- 18824685
TI  - Distinct memories of odor intensity and quality in Drosophila.
AB  - Even in a simple Pavlovian memory task an animal may form several associations
      that can be independently assessed by the appropriate tests. Studying conditioned
      odor discrimination of the fruit fly Drosophila melanogaster we found that
      animals store quality and intensity of an odor as separate memory traces. The
      trace of odor intensity is short-lived, decaying in <3 h. Only the last intensity
      value is stored. In contrast to odor-quality memory, odor-intensity memory does
      not require the rutabaga-dependent cAMP signaling pathway. Flies rely on their
      memory of intensity in a narrow concentration range in which they can generalize
      intensity. Larger concentration differences they treat like different qualities.
      This study shows that the perceptual identity of an odor is based on at least
      three lines of processing in the brain: (i) a memory of odor quality, (ii) a
      memory of odor intensity, and (iii) a range of intensities (and qualities), in
      which the odor is generalized.

PMID- 18824686
TI  - Irreversible chemical steps control intersubunit dynamics during translation.
AB  - The ribosome, a two-subunit macromolecular machine, deciphers the genetic code
      and catalyzes peptide bond formation. Dynamic rotational movement between
      ribosomal subunits is likely required for efficient and accurate protein
      synthesis, but direct observation of intersubunit dynamics has been obscured by
      the repetitive, multistep nature of translation. Here, we report a collection of
      single-molecule fluorescence resonance energy transfer assays that reveal a
      ribosomal intersubunit conformational cycle in real time during initiation and
      the first round of elongation. After subunit joining and delivery of correct
      aminoacyl-tRNA to the ribosome, peptide bond formation results in a rapid
      conformational change, consistent with the counterclockwise rotation of the 30S
      subunit with respect to the 50S subunit implied by prior structural and
      biochemical studies. Subsequent binding of elongation factor G and GTP hydrolysis
      results in a clockwise rotation of the 30S subunit relative to the 50S subunit,
      preparing the ribosome for the next round of tRNA selection and peptide bond
      formation. The ribosome thus harnesses the free energy of irreversible peptidyl
      transfer and GTP hydrolysis to surmount activation barriers to large-scale
      conformational changes during translation. Intersubunit rotation is likely a
      requirement for the concerted movement of tRNA and mRNA substrates during
      translocation.

PMID- 18824687
TI  - Selection of cyclic peptide aptamers to HCV IRES RNA using mRNA display.
AB  - The hepatitis C virus (HCV) is a positive strand RNA flavivirus that is a major
      causative agent of serious liver disease, making new treatment modalities an
      urgent priority. Because HCV translation initiation occurs by a mechanism that is
      fundamentally distinct from that of host mRNAs, it is an attractive target for
      drug discovery. The translation of HCV mRNA is initiated from an internal
      ribosomal entry site (IRES), independent of cap and poly(A) recognition and
      bypassing eIF4F complex formation. We used mRNA display selection technology
      combined with a simple and robust cyclization procedure to screen a peptide
      library of >10(13) different sequences and isolate cyclic peptides that bind with
      high affinity and specificity to HCV IRES RNA. The best peptide binds the IRES
      with subnanomolar affinity, and a specificity of at least 100-fold relative to
      binding to several other RNAs of similar length. The peptide specifically
      inhibits HCV IRES-initiated translation in vitro with no detectable effect on
      normal cap-dependent translation initiation. An 8-aa cyclic peptide retains most
      of the activity of the full-length 27-aa bicyclic peptide. These peptides may be
      useful tools for the study of HCV translation and may have potential for further
      development as an anti-HCV drug.

PMID- 18824688
TI  - Parallel life history evolution in mouthbrooding cichlids from the African Great
      Lakes.
AB  - The existence of ancient deep-water lakes provides an opportunity to study the
      independent adaptation of aquatic organisms to pelagic, benthic, and rocky shore
      habitats. With improving resolution of their phylogenetic relationships, the many
      cichlid fish species endemic to the African Great Lakes Malawi, Tanganyika, and
      Victoria provide a significant resource for the comparative study of such
      evolutionary processes. Here, we show that cichlid lineages colonizing rocky
      shores and pelagic habitats in the different lakes have independently evolved
      larger eggs and lower fecundities than benthic lineages, suggesting parallel
      adaptive life-history evolution. By contrast, other pelagic teleost fishes in
      both marine and freshwater habitats, including African lakes, typically produce
      large numbers of very small eggs. Our results also suggest that decreased
      fecundity and increased egg size not only occurred independently in each lake but
      occurred independently in the colonization of rocky and pelagic habitats.

PMID- 18824689
TI  - Thresholds of hypoxia for marine biodiversity.
AB  - Hypoxia is a mounting problem affecting the world's coastal waters, with severe
      consequences for marine life, including death and catastrophic changes. Hypoxia
      is forecast to increase owing to the combined effects of the continued spread of
      coastal eutrophication and global warming. A broad comparative analysis across a
      range of contrasting marine benthic organisms showed that hypoxia thresholds vary
      greatly across marine benthic organisms and that the conventional definition of 2
      mg O(2)/liter to designate waters as hypoxic is below the empirical sublethal and
      lethal O(2) thresholds for half of the species tested. These results imply that
      the number and area of coastal ecosystems affected by hypoxia and the future
      extent of hypoxia impacts on marine life have been generally underestimated.

PMID- 18824690
TI  - A common variant in the 3'UTR of the GRIK4 glutamate receptor gene affects
      transcript abundance and protects against bipolar disorder.
AB  - Underactivity of the glutamatergic system is an attractive model for the
      pathophysiology of several major mental illnesses. We previously described a
      chromosome abnormality disrupting the kainate class ionotropic glutamate receptor
      gene, GRIK4/KA1, in an individual with schizophrenia and learning disability
      (mental retardation). We also demonstrated in a case-control study that two
      physically separated haplotypes within this gene were significantly associated
      with increased risk of schizophrenia and decreased risk of bipolar disorder,
      respectively. The latter protective haplotype was located at the 3' end of the
      gene. We now report the identification from carriers of the protective haplotype
      of a deletion variant within the 3' untranslated region of the gene. The deletion
      allele also was found to be negatively associated with bipolar disorder in both
      initial (P = 0.00000019) and replication (P = 0.0107) case-control studies.
      Expression studies indicated that deletion-carrying mRNA transcripts were
      relatively more abundant. We postulate that this may be a direct consequence of
      the differences in the RNA secondary structures predicted for the insertion and
      deletion alleles. These data suggest a mechanism whereby the genetic protective
      effect is mediated through increased kainate receptor expression.

PMID- 18824691
TI  - Bioelectrocatalytic hydrogels from electron-conducting metallopolypeptides
      coassembled with bifunctional enzymatic building blocks.
AB  - Here, we present two bifunctional protein building blocks that coassemble to form
      a bioelectrocatalytic hydrogel that catalyzes the reduction of dioxygen to water.
      One building block, a metallopolypeptide based on a previously designed triblock
      polypeptide, is electron-conducting. A second building block is a chimera of
      artificial alpha-helical leucine zipper and random coil domains fused to a
      polyphenol oxidase, small laccase (SLAC). The metallopolypeptide has a helix
      random-helix secondary structure and forms a hydrogel via tetrameric coiled
      coils. The helical and random domains are identical to those fused to the
      polyphenol oxidase. Electron-conducting functionality is derived from the
      divalent attachment of an osmium bis-bipyrdine complex to histidine residues
      within the peptide. Attachment of the osmium moiety is demonstrated by mass
      spectroscopy (MS-MALDI-TOF) and cyclic voltammetry. The structure and function of
      the alpha-helical domains are confirmed by circular dichroism spectroscopy and by
      rheological measurements. The metallopolypeptide shows the ability to make
      electrical contact to a solid-state electrode and to the redox centers of
      modified SLAC. Neat samples of the modified SLAC form hydrogels, indicating that
      the fused alpha-helical domain functions as a physical cross-linker. The fusion
      does not disrupt dimer formation, a necessity for catalytic activity. Mixtures of
      the two building blocks coassemble to form a continuous supramolecular hydrogel
      that, when polarized, generates a catalytic current in the presence of oxygen.
      The specific application of the system is a biofuel cell cathode, but this
      protein-engineering approach to advanced functional hydrogel design is general
      and broadly applicable to biocatalytic, biosensing, and tissue-engineering
      applications.

PMID- 18824692
TI  - The Dam1 ring binds microtubules strongly enough to be a processive as well as
      energy-efficient coupler for chromosome motion.
AB  - Accurate chromosome segregation during mitotic division of budding yeast depends
      on the multiprotein kinetochore complex, Dam1 (also known as DASH). Purified Dam1
      heterodecamers encircle microtubules (MTs) to form rings that can function as
      "couplers," molecular devices that transduce energy from MT disassembly into the
      motion of a cargo. Here we show that MT depolymerization develops a force against
      a Dam1 ring that is sixfold larger than the force exerted on a coupler that binds
      only one side of an MT. Wild-type rings slow depolymerization fourfold, but rings
      that include a mutant Dam1p with truncated C terminus slow depolymerization less,
      consistent with the idea that this tail is part of a strong bond between rings
      and MTs. A molecular-mechanical model for Dam1-MT interaction predicts that
      binding between this flexible tail and the MT wall should cause a Dam1 ring to
      wobble, and Fourier analysis of moving, ring-attached beads corroborates this
      prediction. Comparison of the forces generated against wild-type and mutant
      complexes confirms the importance of tight Dam1-MT association for processive
      cargo movement under load.

PMID- 18824693
TI  - International migration beyond gravity: a statistical model for use in population
      projections.
AB  - International migration will play an increasing role in the demographic future of
      most nations if fertility continues to decline globally. We developed an
      algorithm to project future numbers of international migrants from any country or
      region to any other. The proposed generalized linear model (GLM) used geographic
      and demographic independent variables only (the population and area of origins
      and destinations of migrants, the distance between origin and destination, the
      calendar year, and indicator variables to quantify nonrandom characteristics of
      individual countries). The dependent variable, yearly numbers of migrants, was
      quantified by 43653 reports from 11 countries of migration from 228 origins and
      to 195 destinations during 1960-2004. The final GLM based on all data was
      selected by the Bayesian information criterion. The number of migrants per year
      from origin to destination was proportional to (population of origin)(0.86)(area
      of origin)(-0.21)(population of destination)(0.36)(distance)(-0.97), multiplied
      by functions of year and country-specific indicator variables. The number of
      emigrants from an origin depended on both its population and its population
      density. For a variable initial year and a fixed terminal year 2004, the
      parameter estimates appeared stable. Multiple R(2), the fraction of variation in
      log numbers of migrants accounted for by the starting model, improved gradually
      with recentness of the data: R(2) = 0.57 for data from 1960 to 2004, R(2) = 0.59
      for 1985-2004, R(2) = 0.61 for 1995-2004, and R(2) = 0.64 for 2000-2004. The
      migration estimates generated by the model may be embedded in deterministic or
      stochastic population projections.

PMID- 18824694
TI  - Emergence of hormonal and redox regulation of galectin-1 in placental mammals:
      implication in maternal-fetal immune tolerance.
AB  - Galectin-1 is an anti-inflammatory lectin with pleiotropic regulatory functions
      at the crossroads of innate and adaptive immunity. It is expressed in immune
      privileged sites and is implicated in establishing maternal-fetal immune
      tolerance, which is essential for successful pregnancy in eutherian mammals.
      Here, we show conserved placental localization of galectin-1 in primates and its
      predominant expression in maternal decidua. Phylogenetic footprinting and
      shadowing unveil conserved cis motifs, including an estrogen responsive element
      in the 5' promoter of LGALS1, that were gained during the emergence of placental
      mammals and could account for sex steroid regulation of LGALS1 expression, thus
      providing additional evidence for the role of galectin-1 in immune-endocrine
      cross-talk. Maximum parsimony and maximum likelihood analyses of 27 publicly
      available vertebrate and seven newly sequenced primate LGALS1 coding sequences
      reveal that intense purifying selection has been acting on residues in the
      carbohydrate recognition domain and dimerization interface that are involved in
      immune functions. Parsimony- and codon model-based phylogenetic analysis of
      coding sequences show that amino acid replacements occurred in early mammalian
      evolution on key residues, including gain of cysteines, which regulate immune
      functions by redox status-mediated conformational changes that disable sugar
      binding and dimerization, and that the acquired immunoregulatory functions of
      galectin-1 then became highly conserved in eutherian lineages, suggesting the
      emergence of hormonal and redox regulation of galectin-1 in placental mammals may
      be implicated in maternal-fetal immune tolerance.

PMID- 18824695
TI  - Kinetic regulation of coated vesicle secretion.
AB  - The secretion of vesicles for intracellular transport often relies on the
      aggregation of specialized membrane-bound proteins into a coat able to curve cell
      membranes. The nucleation and growth of a protein coat is a kinetic process that
      competes with the energy-consuming turnover of coat components between the
      membrane and the cytosol. We propose a generic kinetic description of coat
      assembly and the formation of coated vesicles and discuss its implication to the
      dynamics of COP vesicles that traffic within the Golgi and with the endoplasmic
      reticulum. We show that stationary coats of fixed area emerge from the
      competition between coat growth and the recycling of coat components, in a
      fashion resembling the treadmilling of cytoskeletal filaments. We further show
      that the turnover of coat components allows for a highly sensitive switching
      mechanism between a quiescent and a vesicle producing membrane, upon a slowing
      down of the exchange kinetics. We claim that the existence of this switching
      behavior, also triggered by factors, such as the presence of cargo and variation
      of the membrane mechanical tension, allows for efficient regulation of vesicle
      secretion. We propose a model, supported by different experimental observations,
      in which vesiculation of secretory membranes is impaired by the energy-consuming
      desorption of coat proteins, until the presence of cargo or other factors
      triggers a dynamical switch into a vesicle producing state.

PMID- 18824696
TI  - The microRNA miR-8 is a conserved negative regulator of Wnt signaling.
AB  - Wnt signaling plays many important roles in animal development. This
      evolutionarily conserved signaling pathway is highly regulated at all levels. To
      identify regulators of the Wnt/Wingless (Wg) pathway, we performed a genetic
      screen in Drosophila. We identified the microRNA miR-8 as an inhibitor of Wg
      signaling. Expression of miR-8 potently antagonizes Wg signaling in vivo, in part
      by directly targeting wntless, a gene required for Wg secretion. In addition, miR
      8 inhibits the pathway downstream of the Wg signal by repressing TCF protein
      levels. Another positive regulator of the pathway, CG32767, is also targeted by
      miR-8. Our data suggest that miR-8 potently antagonizes the Wg pathway at
      multiple levels, from secretion of the ligand to transcription of target genes.
      In addition, mammalian homologues of miR-8 promote adipogenesis of marrow stromal
      cells by inhibiting Wnt signaling. These findings indicate that miR-8 family
      members play an evolutionarily conserved role in regulating the Wnt signaling
      pathway.

PMID- 18824697
TI  - Structural basis for RNA recognition by a type II poly(A)-binding protein.
AB  - We identified a functional domain (XlePABP2-TRP) of Xenopus laevis embryonic type
      II poly(A)-binding protein (XlePABP2). The NMR structure of XlePABP2-TRP revealed
      that the protein is a homodimer formed by the antiparallel association of beta
      strands from the single RNA recognition motif (RRM) domain of each subunit. In
      each subunit of the homodimer, the canonical RNA recognition site is occluded by
      a polyproline motif. Upon poly(A) binding, XlePABP2-TRP undergoes a dimer-monomer
      transition that removes the polyproline motif from the RNA recognition site and
      allows it to be replaced by the adenosine nucleotides of poly(A). Our results
      provide high-resolution structural information concerning type II PABPs and an
      example of a single RRM domain protein that transitions from a homodimer to a
      monomer upon RNA binding. These findings advance our understanding of RRM domain
      regulation, poly(A) recognition, and are relevant to understanding how type II
      PABPs function in mRNA processing and human disease.

PMID- 18824698
TI  - Major ongoing stroke trials.

PMID- 18824699
TI  - Documentation of thyroid function in clinical studies with sunitinib: why does it
      matter?

PMID- 18824700
TI  - Exploiting the apoptotic route for cancer treatment: a single hit will rarely
      result in a home run.

PMID- 18824701
TI  - Clinically applicable models to characterize BRCA1 and BRCA2 variants of
      uncertain significance.
AB  - PURPOSE: Twenty percent of individuals with a strong family and/or personal
      history of breast and ovarian cancer carry a deleterious mutation in BRCA1 or
      BRCA2. Identification of mutations in these genes is extremely beneficial for
      patients pursuing risk reduction strategies. Approximately 7% of individuals who
      have genetic testing of BRCA1 and BRCA2 carry a variant of uncertain significance
      (VUS), making clinical management less certain. The majority of identified VUS
      occur only in one to two individuals; these variants are not able to be
      classified using current classification models with segregation analysis
      components. METHODS: To develop a clinically applicable method that can predict
      the pathogenicity of VUS that does not require familial information or
      segregation analysis, we identified characteristics of breast or ovarian tumors
      that distinguished sporadic tumors from tumors with BRCA1 or BRCA2 mutations.
      Study participants included individuals with known deleterious mutations in BRCA1
      or BRCA2 and individuals with classified or unclassified BRCA variants. RESULTS:
      We applied the models to 57 tumors with 43 different deleterious BRCA mutations
      and 57 tumors with 54 unique classified and unclassified BRCA variants. Of the 33
      previously unclassified VUS studied, we found evidence of neutrality for 21.
      CONCLUSION: Our models showed 98% sensitivity and 76% specificity for predicting
      classified DNA changes. We classified 64% of unknown variants as neutral.
      Classification of VUS as neutral will have immediate benefit for those
      individuals and their family members. These models are adaptable for the clinic
      and will be useful for individuals with limited available family history.

PMID- 18824702
TI  - Phase I and pharmacokinetic study of YM155, a small-molecule inhibitor of
      survivin.
AB  - PURPOSE: To determine the maximum-tolerated dose (MTD) and assess the safety,
      pharmacokinetics, and preliminary evidence of antitumor activity of YM155, a
      small-molecule inhibitor of survivin. PATIENTS AND METHODS: Patients with
      advanced solid malignancies or lymphoma were treated with escalating doses of
      YM155 administered by 168-hour continuous intravenous infusion (CIVI). Plasma and
      urine samples were assayed to determine pharmacokinetic parameters and excretion.
      RESULTS: Forty-one patients received 127 cycles of YM155 at doses ranging from
      1.8 to 6.0 mg/m(2)/d by 168-hour CIVI every 3 weeks. Overall, the most common
      grade 1 to 2 toxicities were stomatitis, pyrexia, and nausea, whereas grade 3 and
      4 toxicities were rare. Reversible elevation in serum creatinine in two patients,
      with one developing acute tubular necrosis, was dose-limiting at 6.0 mg/m(2). The
      MTD was 4.8 mg/m(2). At the MTD, the mean steady-state concentration, clearance,
      volume of distribution at steady-state, and terminal elimination half-life were
      7.7 ng/mL, 47.7 L/h, 1,763 L, and 26 hours, respectively. One complete and two
      partial responses lasting 8, 24+ and 48+ months occurred in three patients with
      non-Hodgkin's lymphoma, two patients with hormone- and docetaxel-refractory
      prostate cancer had prostate-specific antigen responses, and one patient with non
      small-cell lung cancer had a minor response. CONCLUSION YM155 can be administered
      safely at 4.8 mg/m(2)/d 168 hours CIVI every 3 weeks. The absence of severe
      toxicities, attainment of plasma concentrations active in preclinical models, and
      compelling antitumor activity warrant further disease-directed studies of this
      agent alone and in combination with chemotherapy in a broad array of tumors.

PMID- 18824703
TI  - Implantable pump for long-term chemotherapy administration via the hepatic
      artery: has it fulfilled its promise?

PMID- 18824704
TI  - New lessons from "old" chemotherapy in colorectal cancer.

PMID- 18824705
TI  - Does computed tomography or positron emission tomography response after
      neoadjuvant chemotherapy for resectable non-small-cell lung cancer predict
      survival?

PMID- 18824706
TI  - Oxaliplatin plus irinotecan compared with irinotecan alone as second-line
      treatment after single-agent fluoropyrimidine therapy for metastatic colorectal
      carcinoma.
AB  - PURPOSE To determine whether irinotecan plus oxaliplatin (IROX) is superior to
      irinotecan alone in patients with metastatic colorectal cancer (CRC) previously
      treated with single-agent fluoropyrimidines. PATIENTS AND METHODS A phase III,
      randomized, open-label, multicenter study of patients with metastatic or
      recurrent CRC that had progressed or recurred during or after adjuvant or first
      line fluoropyrimidines (fluorouracil/leucovorin or capecitabine, the latter only
      for metastatic CRC). Patients received IROX (irinotecan 200 mg/m(2) plus
      oxaliplatin 85 mg/m(2)) or irinotecan alone (350 mg/m(2)) every 3 weeks. RESULTS:
      At the data cutoff (when 447 of 628 randomly assigned patients had died), median
      overall survival was 13.4 months (95% CI, 12.4 to 14.7 months) and 11.1 month
      (95% CI, 10.0 to 12.7 months) in the IROX and irinotecan groups, respectively
      (hazard ratio = 0.78; 95% CI, 0.65 to 0.94; P = .0072). Overall response rate
      (22% v 7%, respectively; P < .0001), median time to progression (5.3 v 2.8
      months, respectively; P < .0001), and improvement in tumor-related symptoms (32%
      v 19%, respectively; P = .0072) were also improved with IROX as compared with
      irinotecan. With the exception of granulocytopenia (25% v 13%), diarrhea (28% v
      23%), and sensory disturbances (5% v 0%), grade 3 to 4 toxicities were comparable
      between the IROX and irinotecan groups, respectively. CONCLUSION IROX is an
      effective treatment for metastatic CRC that has progressed after first-line
      fluoropyrimidine therapy. IROX improves efficacy compared with irinotecan alone,
      providing an additional option in the postadjuvant or second-line treatment
      setting for patients who experience treatment failure with single-agent
      fluoropyrimidine therapy.

PMID- 18824707
TI  - Association between hepatitis B virus and pancreatic cancer.
AB  - PURPOSE: Hepatitis B virus (HBV) and hepatitis C virus (HCV) are considered to be
      hepatotropic and are a major cause of hepatocellular carcinoma. However, little
      is known about the role of HBV and HCV infection in other malignancies. This
      study aimed to determine whether HBV and HCV infections increase the risk for
      pancreatic cancer development. PATIENTS AND METHODS: At The University of Texas
      M. D. Anderson Cancer Center, Houston, TX, we recruited 476 patients with
      pathologically confirmed adenocarcinoma of the pancreas and 879 age-, sex-, and
      race-matched healthy controls. Blood samples were tested for the presence of HCV
      antibodies (anti-HCV), HBV surface antigen (HBsAg), antibodies against HBV core
      antigen (anti-HBc), and antibodies against HBsAg (anti-HBs). The positive samples
      were retested by two confirmatory tests. An unconditional multivariable logistic
      regression analysis was used to estimate adjusted odds ratios (AORs). RESULTS:
      Anti-HCV was positive in seven cases (1.5%) and nine controls (1%). Anti-HBc was
      positive in 36 cases (7.6%) and 28 controls (3.2%). The estimated AORs and 95%
      CIs were as follows: anti-HCV-positive, 0.9 (95% CI, 0.3 to 2.8), anti-HBc
      positive, 2.5 (95% CI, 1.5 to 4.2), anti-HBc-positive/anti-HBs-positive, 2.3 (95%
      CI, 1.2 to 4.2), and anti-HBc-positive/anti-HBs-negative, 4 (95% CI, 1.4 to
      11.1). Risk modification by past exposure to HBV was observed among diabetics
      (AOR, 7.1; 95% CI, 1.7 to 28.7). CONCLUSION: Past exposure to HBV may be
      associated with pancreatic cancer development. Should such findings be confirmed
      by other studies, it may offer important insights into the etiology of pancreatic
      cancer and may suggest the need to consider prevention of HBV reactivation among
      patients with HBV-related pancreatic cancer during chemotherapy.

PMID- 18824708
TI  - Dynamic contrast-enhanced magnetic resonance imaging pharmacodynamic biomarker
      study of sorafenib in metastatic renal carcinoma.
AB  - PURPOSE: Sorafenib is an antiangiogenic agent with activity in renal cancer. We
      conducted a randomized trial to investigate dynamic contrast magnetic resonance
      imaging (DCE-MRI) as a pharmacodynamic biomarker. PATIENTS AND METHODS: Patients
      were randomly assigned to placebo or 200 or 400 mg twice per day of sorafenib.
      DCE-MRI was performed at baseline and 4 weeks. DCE-MRI parameters, area under the
      contrast concentration versus time curve 90 seconds after contrast injection
      (IAUC(90)), and volume transfer constant of contrast agent (K(trans)) were
      calculated for a metastatic site selected in a blinded manner. Primary end point
      was change in K(trans). RESULTS: Of the 56 assessable patients, 48 underwent two
      MRIs; 44 MRIs were assessable for study end points. Mean K(trans) log ratios were
      0.131 (standard deviation [SD], 0.315), -0.148 (SD, 0.382), -0.271 (SD, 0.499) in
      placebo, 200- and 400-mg cohorts, respectively (P = .0077 for trend)
      corresponding to changes of +14%, -14%, and -24%. IAUC(90) log ratios were 0.041
      (SD, 0.197), -0.040 (SD, 0.132), -0.356 (SD, 0.411), respectively (P = .0003 for
      trend), corresponding to changes of +4%, -4%, and -30%. Using a log-rank test,
      IAUC(90) and K(trans) changes were not associated with progression-free survival
      (PFS). Patients with high baseline K(trans) had a better PFS (P = .027).
      CONCLUSION: IAUC(90) and K(trans) are pharmacodynamic biomarkers for sorafenib,
      but variability is high and magnitude of effect is less than previously reported.
      Changes in DCE-MRI parameters after 4 weeks of sorafenib are not predictive of
      PFS, suggesting that these biomarkers are not surrogate end points. The value of
      baseline K(trans) as a prognostic or predictive biomarker requires additional
      study.

PMID- 18824709
TI  - Computed tomography response, but not positron emission tomography scan response,
      predicts survival after neoadjuvant chemotherapy for resectable non-small-cell
      lung cancer.
AB  - PURPOSE: Tumor response is considered a surrogate marker of survival. We
      investigated whether tumor response based on computed tomography (CT) scan or
      whole-body [(18)F]fluorodeoxyglucose positron emission tomography (PET) scan
      after neoadjuvant chemotherapy for resectable non-small-cell lung cancer (NSCLC)
      is prognostic of survival. PATIENTS AND METHODS: Two consecutive phase II
      clinical trials were jointly analyzed. Patients underwent CT and PET scans before
      and after completion of neoadjuvant chemotherapy, followed by surgery. RESULTS:
      Eighty-nine patients were included. Patients with a partial or complete response
      based on Response Evaluation Criteria in Solid Tumors categories (n = 33) had a
      better overall survival than those with stable or progressive disease (n = 56;
      median survival time, not reached v 36 months, respectively; P = .04). Of all
      patients, those with response in the highest quartile had 1- and 2-year survival
      rates of 100% and 81%, respectively, compared with 77% and 61%, respectively,
      among patients in the lowest quartile. However, on the basis of visual analysis
      of PET scan, patients with a metabolic response (n = 28) had no significant
      difference in survival compared with patients without response (n = 61; median
      survival time, 35.6 months v not reached, respectively; P = .94). In addition, on
      the basis of a semiquantitative analysis of PET scan, using at least 30%
      reduction in tumor metabolism as a response (n = 59), we also found no
      significant difference in survival among those with or without response.
      CONCLUSION: Among patients with resectable NSCLC treated with neoadjuvant
      chemotherapy, we found no evidence that tumor response by PET scan after
      chemotherapy is prognostic of survival; however, response by CT scan was
      associated with better survival.

PMID- 18824710
TI  - Longitudinal changes in obesity and body mass index among adult survivors of
      childhood acute lymphoblastic leukemia: a report from the Childhood Cancer
      Survivor Study.
AB  - PURPOSE: We examined the rate of increase in the body mass index (BMI; kg/m(2))
      after final height attainment in survivors of acute lymphoblastic leukemia (ALL)
      and a noncancer comparison group. METHODS: Childhood Cancer Survivor Study (CCSS)
      is a retrospectively ascertained cohort study that prospectively tracks the
      health status of adults who were diagnosed with childhood cancer between 1970 and
      1986 and a comparison group of siblings. Changes in BMI from baseline enrollment
      to time of completion of follow-up (mean interval, 7.8 years) were calculated for
      1,451 ALL survivors (mean age, 32.3 years at follow-up) and 2,167 siblings of
      childhood cancer survivors (mean age, 35.9 years). RESULTS: The mean BMI of the
      CCSS sibling comparison group increased with age (women, 0.25 units/yr, 95% CI,
      0.22 to 0.28 units; men, 0.23 units/yr, 95% CI, 0.20 to 0.25 units). Compared
      with CCSS siblings, ALL survivors who were treated with cranial radiation therapy
      (CRT) had a significantly greater increase in BMI (women, 0.41 units/yr, 95% CI,
      0.37 to 0.45 units; men, 0.29 units/yr; 95% CI, 0.26 to 0.32 units). The rate of
      BMI increase was not significantly increased for ALL survivors who were treated
      with chemotherapy alone. Younger age at CRT exposure significantly modified risk.
      CONCLUSION: CRT used in the treatment of childhood ALL is associated with a
      greater rate of increasing BMI, particularly among women treated with CRT during
      the first decade of life. Health care professionals should be aware of this risk
      and interventions to reduce or manage weight gain are essential in this high-risk
      population.

PMID- 18824711
TI  - Availability and use of palliative care and end-of-life services for pediatric
      oncology patients.
AB  - PURPOSE: Palliative care prevents or relieves the symptoms caused by life
      threatening medical conditions. Previous surveys have shown both underuse and
      lack of availability of these services for children with cancer throughout North
      America. We sought to investigate the current practices and resources surrounding
      palliative and end-of-life care among participating institutions of the
      Children's Oncology Group (COG). METHODS: A survey regarding practices and
      resources was developed by the COG palliative care subcommittee and was sent to
      all 232 institutions to complete for the calendar year 2005. RESULTS: The survey
      was completed by 81% of the institutions. Per institution, there were a mean of
      64.6 newly diagnosed patients and 17.7 patients experiencing relapse. A
      palliative care team was available in 58% of institutions, a pain service in 90%,
      a hospice in 60%, a psychosocial support team in 80%, and a bereavement program
      in 59%. Complementary and alternative medicine was available in 39% of
      institutions and in 95% of the COG institution's community. Most services, even
      when available, were not well used by patients. CONCLUSION: Despite the well
      established benefit of pediatric palliative care, it is only offered in 58% of
      COG institutions caring for children with cancer. In an era where the benefit of
      palliative care has been clearly established, this number should approach 100%.
      Efforts should be directed toward understanding barriers to provision of such
      services, so that they are available and well used at all childhood cancer
      centers.

PMID- 18824712
TI  - Phase II study of imatinib in patients with recurrent gliomas of various
      histologies: a European Organisation for Research and Treatment of Cancer Brain
      Tumor Group Study.
AB  - PURPOSE: To evaluate the safety and the efficacy of imatinib in recurrent
      malignant gliomas. PATIENTS AND METHODS: This was a single-arm, phase II study.
      Eligible patients had recurrent glioma after prior radiotherapy with an enhancing
      lesion on magnetic resonance imaging. Three different histologic groups were
      studied: glioblastomas (GBM), pure/mixed (anaplastic) oligodendrogliomas (OD),
      and low-grade or anaplastic astrocytomas (A). Imatinib was started at a dose of
      600 mg/d with dose escalation to 800 mg in case of no toxicity; during the trial
      this dose was increased to 800 mg/d with escalation to 1,000 mg/d. Trial design
      was one-stage Fleming; both an objective response and 6 months of progression
      free survival (PFS) were considered a successful outcome to treatment. RESULTS: A
      total of 112 patients (51 patients with GBM, 25 patients with A, and 36 patients
      with OD) were enrolled. Imatinib was in general well tolerated. The median number
      of cycles was 2.0 (range, 1 to 43 cycles). Five patients had an objective partial
      response, including three patients with GBM; all had 6 months of PFS. The 6-month
      PFS rate was 16% (95% CI, 8.0% to 34.0%) in GBM, 4.0% (95% CI, 0.3% to 15.0%) in
      OD, and 9% (95% CI, 2.0% to 25.0%) in A. The exposure to imatinib was
      significantly lower in patients using enzyme-inducing antiepileptic drugs. The
      presence of ABCG2 point mutations were not correlated with pharmacokinetic
      findings. No somatic activating mutations of KIT or platelet-derived growth
      factor receptor-A or -B were found. CONCLUSION: In the dose range of 600 to 1,000
      mg/d, single-agent imatinib is well tolerated but has limited antitumor activity
      in patients with recurrent gliomas.

PMID- 18824713
TI  - Psychosocial factors and survival of young women with breast cancer: a population
      based prospective cohort study.
AB  - PURPOSE: Most women with early-stage breast cancer believe that psychosocial
      factors are an important influence over whether their cancer will recur. Studies
      of the issue have produced conflicting results. PATIENTS AND METHODS: A
      population-based sample of 708 Australian women diagnosed before age 60 years
      with nonmetastatic breast cancer was observed for a median of 8.2 years.
      Depression and anxiety, coping style, and social support were assessed at a
      median of 11 months after diagnosis. Hazard ratios for distant disease-free
      survival (DDFS) and overall survival (OS) associated with psychosocial factors
      were estimated separately using Cox proportional hazards survival models, with
      and without adjustment for known prognostic factors. RESULTS: Distant recurrence
      occurred in 209 (33%) of 638 assessable patients, and 170 (24%) of 708 patients
      died during the follow-up period. There were no statistically significant
      associations between any of the measured psychosocial factors and DDFS or OS from
      the adjusted analyses. From unadjusted analyses, associations between greater
      anxious preoccupation and poorer DDFS and OS were observed (P = .02). These
      associations were no longer evident after adjustment for established prognostic
      factors; greater anxious preoccupation was associated with younger age at
      diagnosis (P = .03), higher tumor grade (P = .02), and greater number of involved
      axillary nodes (P = .008). CONCLUSION: The findings do not support the measured
      psychosocial factors being an important influence on breast cancer outcomes.
      Interventions for adverse psychosocial factors are warranted to improve quality
      of life but should not be expected to improve survival.

PMID- 18824716
TI  - Primary mediastinal germ cell tumor evolving into an extramedullary acute
      megakaryoblastic leukemia causing cord compression.

PMID- 18824714
TI  - Association of vascular endothelial growth factor and vascular endothelial growth
      factor receptor-2 genetic polymorphisms with outcome in a trial of paclitaxel
      compared with paclitaxel plus bevacizumab in advanced breast cancer: ECOG 2100.
AB  - PURPOSE: No biomarkers have been identified to predict outcome with the use of an
      antiangiogenesis agent for cancer. Vascular endothelial growth factor (VEGF)
      genetic variability has been associated with altered risk of breast cancer and
      variable promoter activity. Therefore, we evaluated the association of VEGF
      genotype with efficacy and toxicity in E2100, a phase III study comparing
      paclitaxel versus paclitaxel plus bevacizumab as initial chemotherapy for
      metastatic breast cancer. PATIENTS AND METHODS: DNA was extracted from tumor
      blocks of patients from E2100. Three hundred sixty-three samples were available
      to evaluate associations between genotype and outcome. Genotyping was performed
      for selected polymorphisms in VEGF and VEGF receptor 2. Testing for associations
      between each polymorphism and efficacy and toxicity was performed. RESULTS: The
      VEGF-2578 AA genotype was associated with a superior median overall survival (OS)
      in the combination arm when compared with the alternate genotypes combined
      (hazard ratio = 0.58; 95% CI, 0.36 to 0.93; P = .023). The VEGF-1154 A allele
      also demonstrated a superior median OS with an additive effect of each active
      allele in the combination arm but not the control arm (hazard ratio = 0.62; 95%
      CI, 0.46 to 0.83; P = .001). Two additional genotypes, VEGF-634 CC and VEGF-1498
      TT, were associated with significantly less grade 3 or 4 hypertension in the
      combination arm when compared with the alternate genotypes combined (P = .005 and
      P = .022, respectively). CONCLUSION: Our data support an association between VEGF
      genotype and median OS as well as grade 3 or 4 hypertension when using
      bevacizumab in metastatic breast cancer.

PMID- 18824717
TI  - Metastasis of a histologically benign--appearing meningioma to the iliac bone.

PMID- 18824718
TI  - Small-cell lung carcinoma presenting with otalgia and hearing impairment.

PMID- 18824719
TI  - Bevacizumab in advanced colorectal cancer: a challenge to the current paradigm.

PMID- 18824720
TI  - Does rituximab really induce hepatitis C virus reactivation?

PMID- 18824721
TI  - Cardiac malformations are associated with altered expression of vascular
      endothelial growth factor and endothelial nitric oxide synthase genes in embryos
      of diabetic mice.
AB  - The aim of this study was to investigate the role of nitric oxide (NO), and the
      expression of endothelial nitric oxide synthase (eNOS) and vascular endothelial
      growth factor (VEGF) genes in developing hearts at embryonic day 13.5 of embryos
      from diabetic mice. The protein and mRNA expression levels of eNOS and VEGF were
      significantly altered in the developing hearts of embryos from diabetic mice. The
      NO level was significantly decreased, whereas the VEGF concentration was
      significantly increased in the developing hearts of the embryos from diabetic
      mice. In vitro study showed a significant reduction in eNOS expression and cell
      proliferation in cardiac myoblast cells exposed to high glucose concentrations.
      Further, high glucose induced apoptosis in myoblast cells. Ultrastructural
      changes characteristics of apoptosis, including cell blebbing, aggregation of
      ribosomes and vacuoles in the cytoplasm were also evident in myoblast cells
      exposed to high glucose. It is suggested that hyperglycemia alters the expression
      of eNOS and VEGF genes that are involved in the regulation of cell growth and
      vasculogenesis, thereby contributing to the cardiac malformations seen in embryos
      from diabetic mice.

PMID- 18824722
TI  - Immunomodulatory effects of feed-borne Fusarium mycotoxins in chickens infected
      with coccidia.
AB  - The potential for Fusarium mycotoxins to modulate immunity was studied in
      chickens raised to 10 weeks of age using an enteric coccidial infection model.
      Experimental diets included: control, diets containing grains naturally
      contaminated with Fusarium mycotoxins, and diets containing contaminated grains +
      0.2% polymeric glucomannan mycotoxin adsorbent (GMA). Contaminated diets
      contained up to 3.8 microg/g deoxynivalenol (DON), 0.3 microg/g 15-acetyl DON and
      0.2 microg/g zearalenone. An optimized mixture (inducing lesions without
      mortality) of Eimeria acervulina, E. maxima and E. tenella was used to challenge
      birds at 8 weeks of age. Immune parameters were studied prior to challenge, at
      the end of the challenge period (7 days post-inoculation, PI), and at the end of
      the recovery period (14 days PI). Total serum immunoglobulin (Ig) A and IgG
      concentrations in challenged birds fed the contaminated diet were higher than
      controls at the end of the challenge period. Serum concentration of IgA, but not
      IgG, was significantly decreased at the end of the recovery period in birds fed
      the contaminated diet. The percentage of CD4+ and CD8+ cell populations in blood
      mononuclear cells decreased significantly at the end of the challenge period in
      birds fed the control or the contaminated diet compared to their percentages
      prior to challenge. The pre-challenge percentage of CD8+ population was restored
      at the end of the recovery period only in birds fed the control diet. Interferon
      gamma (IFN-gamma) gene expression in caecal tonsils was up-regulated in
      challenged birds fed the contaminated diet at the end of the challenge period. No
      significant effect of diet was observed on oocyst counts despite the changes in
      the studied immune parameters. It was concluded that Fusarium mycotoxins modulate
      the avian immune system. This modulation involves alteration of gene expression
      but apparently does not enhance susceptibility or resistance to a primary
      coccidial challenge.

PMID- 18824723
TI  - Methanolic extract of Cuminum cyminum inhibits ovariectomy-induced bone loss in
      rats.
AB  - Several animal and clinical studies have shown that phytoestrogens, plant-derived
      estrogenic compounds, can be useful in treating postmenopausal osteoporosis.
      Phytoestrogens and phytoestrogen-containing plants are currently under active
      investigation for their role in estrogen-related disorders. The present study
      deals with anti-osteoporotic evaluation of phytoestrogen-rich plant Cuminum
      cyminum, commonly known as cumin. Adult Sprague-Dawley rats were bilaterally
      ovariectomized (OVX) and randomly assigned to 3 groups (10 rats/group).
      Additional 10 animals were sham operated. OVX and sham control groups were orally
      administered with vehicle while the other two OVX groups were administered 0.15
      mg/kg estradiol and 1 g/kg of methanolic extract of Cuminum cyminum fruits (MCC)
      in two divided doses for 10 weeks. At the end of the study blood, bones and uteri
      of the animals were collected. Serum was evaluated for calcium, phosphorus,
      alkaline phosphatase and tartarate resistant acid phosphatase. Bone density, ash
      density, mineral content and mechanical strength of bones were evaluated.
      Scanning electron microscopic (SEM) analysis of bones (tibia) was performed.
      Results were analyzed using ANOVA and Tukeys multiple comparison test. MCC (1
      g/kg, p.o.) significantly reduced urinary calcium excretion and significantly
      increased calcium content and mechanical strength of bones in comparison to OVX
      control. It showed greater bone and ash densities and improved microarchitecture
      of bones in SEM analysis. Unlike estradiol it did not affect body weight gain and
      weight of atrophic uterus in OVX animals. MCC prevented ovariectomy-induced bone
      loss in rats with no anabolic effect on atrophic uterus. The osteoprotective
      effect was comparable with estradiol.

PMID- 18824724
TI  - Mucosal IgA increase in rats by continuous CLA feeding during suckling and early
      infancy.
AB  - The aim of this work was to establish the effect of the cis9,trans11 conjugated
      linoleic acid (CLA) isomer on mucosal immunity during early life in rats, a
      period when mucosal immunoglobulin production is poorly developed, as is also the
      case in humans. CLA supplementation was performed during three life periods:
      gestation, suckling, and early infancy. The immune status of supplemented animals
      was evaluated at two time points: at the end of the suckling period (21-day-old
      rats) and 1 week after weaning (28-day-old rats). Secretory IgA was quantified in
      intestinal washes from 28-day-old rats by ELISA technique. IgA, TGFbeta, and
      PPARgamma mRNA expression was measured in small intestine and colon by real time
      PCR, using Taqman specific probes and primers. IgA mucosal production was
      enhanced in animals supplemented with CLA during suckling and early infancy: in
      28-day-old rats, IgA mRNA expression was increased in small intestine and colon
      by approximately 6- and 4-fold, respectively, and intestinal IgA protein by
      approximately 2-fold. TGFbeta gene expression was independent of age and type of
      tissue considered, and was not modified by dietary CLA. Gene expression of
      PPARgamma, a possible mediator of CLA's effects was also upregulated in animals
      receiving CLA during early life. In conclusion, dietary supplementation with CLA
      during suckling and extended to early infancy enhances development of the
      intestinal immune response in rats.

PMID- 18824725
TI  - Upper and lower tear menisci on contact lenses.
AB  - PURPOSE: The purpose of this study was to measure upper and lower tear menisci on
      contact lenses using real time optical coherence tomography (OCT). METHODS: Both
      eyes of 20 adapted contact lens wearers were imaged when they wore two types of
      silicone hydrogel lenses, balafilcon A on one eye and galyfilcon A on the other
      eye. The height, radius, and area of upper and lower tear menisci were obtained
      before, immediately after, and 20 minutes after lens wear on two consecutive
      days. On a third visit, the lenses were switched between eyes and an
      investigative lubricant was instilled after 4 hours of lens wear. OCT images were
      obtained as before and additionally at 1 and 4 hours after lens insertion.
      Imaging was also conducted immediately after lubricant instillation and 20
      minutes post-instillation. RESULTS: There were no significant differences in the
      measured variables between lenses (P > 0.05) and between consecutive visits (P >
      0.05). The menisci around both eyelids immediately after lens insertion were
      significantly greater than that before (P < 0.005). By 20 minutes after lens
      insertion, all variables had returned to baseline values and remained that way
      for at least 4 hours. Immediately after the instillation of the lubricant at 4
      hours, meniscus variables increased (P < 0.001), but recovery to baseline
      occurred within 20 minutes. CONCLUSIONS: It is feasible to use OCT in the
      measurement of both upper and lower tear menisci on contact lenses in situ. Tear
      menisci increased on insertion of contact lenses and on instillation of
      lubricants. However baseline values were re-established with 20 minutes.

PMID- 18824726
TI  - Steroid-induced ocular hypertension in normal sheep.
AB  - PURPOSE: To determine whether the ovine eye develops elevation of intraocular
      pressure (IOP) in response to corticosteroid applied topically. METHODS: IOP was
      monitored by Perkins applanation tonometry in a group of 18 sheep receiving
      topically administered 0.5% prednisolone acetate in one eye (experimental), three
      times daily, for a period of 3 or four 4 weeks after the establishment of
      baseline IOP values. Perkins readings were converted to actual mm Hg using a
      calibration curve derived from in vivo manometric measurements. IOP was monitored
      for an additional 1 to 3 weeks after discontinuation of corticosteroid treatment.
      RESULTS: Baseline IOP in normal sheep was 10.6+/-1.4 mm Hg (mean +/- SD; n=36
      eyes). The IOP of the experimental eyes began to increase after 1 week of
      prednisolone treatment in all sheep and reached a peak 1 week later (27.5 mm Hg
      experimental vs. 11.7 mm Hg fellow, control eye; P<0.001). After the
      discontinuation of corticosteroid instillation, the IOP of the treated eyes
      declined to the baseline values over the course of 1 to 3 weeks. CONCLUSIONS:
      Ovine eyes exhibit a robust steroid-induced ocular hypertensive response, with
      100% occurrence in this trial. The mechanisms of steroid-induced glaucoma may be
      related to those involved in primary open-angle glaucoma and could provide
      insight into primary open-angle and clues to its treatment.

PMID- 18824727
TI  - Chromosome 3 intratumor heterogeneity in uveal melanoma.
AB  - PURPOSE: To investigate the presence of focal or diffuse heterogeneity of
      monosomy 3 in uveal melanoma, by using fluorescence in situ hybridization (FISH).
      METHODS: Direct interphase FISH in a series of 151 uveal melanomas revealed 82
      tumors with loss of chromosome 3. Tumors with monosomy 3 were suspected to be
      heterogeneous if there were low percentages of monosomy 3, triploid clones,
      inconsistencies between FISH on centromere 3 and the long arm of chromosome 3, or
      discrepancies between fine-needle-aspiration biopsies (FNABs) and the main tumor.
      These tumors (n=16), all choroidal melanomas, were selected and analyzed for
      intratumor heterogeneity by using FISH on paraffin-embedded tissue sections.
      RESULTS: Different sections of each tumor were evaluated with FISH: 6 tumors
      showed monosomy 3 in the same percentage throughout the tumor, and 10 showed
      multiple clones with different percentages of monosomy 3. However, these tumors
      did not show focal heterogeneity with respect to chromosome 3 status, and
      differences in monosomy 3 distribution between the base and apex of the tumor
      could not be identified. CONCLUSIONS: Although a small number of uveal melanomas
      show heterogeneity for chromosome 3, it does not affect survival. In the presence
      of triploid clones, the loss of chromosome 3 is more difficult to interpret. In
      general, tumor biopsies in uveal melanoma provide an accurate prediction of the
      patient's prognosis.

PMID- 18824728
TI  - Rod and rod-driven function in achromatopsia and blue cone monochromatism.
AB  - PURPOSE: To evaluate rod photoreceptor and postreceptor retinal function in
      pediatric patients with achromatopsia (ACHR) and blue cone monochromatism (BCM)
      using contemporary electroretinographic (ERG) procedures. METHODS: Fifteen
      patients (age range, 1-20 years) with ACHR and six patients (age range, 4-22
      years) with BCM were studied. ERG responses to full-field stimuli were obtained
      in scotopic and photopic conditions. Rod photoreceptor (S(rod), R(rod)) and rod
      driven postreceptor (log sigma, V(max)) response parameters were calculated from
      the a-wave and b-wave. ERG records were digitally filtered to demonstrate the
      oscillatory potentials (OPs); a sensitivity parameter, log SOPA(1/2), and an
      amplitude parameter, SOPA(max), were used to characterize the OP response.
      Response parameters were compared with those of 12 healthy control subjects.
      RESULTS: As expected, photopic responses were nondetectable in patients with ACHR
      and BCM. In addition, mean scotopic photoreceptor (R(rod)) and postreceptor
      (V(max) and SOPA(max)) amplitude parameters were significantly reduced compared
      with those in healthy controls. The flash intensity required to evoke a half
      maximum b-wave amplitude (log sigma) was significantly increased. CONCLUSIONS:
      Results of this study provide evidence that deficits in rod and rod-mediated
      function occur in the primary cone dysfunction syndromes ACHR and BCM.

PMID- 18824729
TI  - Role of medial orbital wall morphologic properties in orbital blow-out fractures.
AB  - PURPOSE: This study compares medial orbital wall supporting structures in
      patients with isolated inferior and medial wall fractures. METHODS: The
      morphologic properties in all consecutive patients with periocular trauma who
      underwent orbital computed tomography (CT) scans from January 2004 to March 2006
      were reviewed. On CT scans, the size of the fracture, the number of ethmoid air
      cell septa, and the length and height of the lamina papyracea were measured.
      RESULTS: In 118 patients without orbital wall fracture, there were no bilateral
      differences in the measured structures. We took measurements from the opposite
      site in patients with fractures in whom it was difficult to visualize the
      structures at the fractured site. Seventy patients with medial wall fractures and
      37 with inferior wall fractures showed no differences in sex, side of impact,
      etiology of the trauma, association with intraocular injuries, fracture size,
      anterior and posterior height, anteroposterior length, or the area of the lamina
      papyracea. In contrast, the number of ethmoid air cell septa was significantly
      lower (3.09+/-0.86 vs. 3.62+/-0.79, P=0.002) and the lamina papyracea area
      supported per ethmoid air cell septum was significantly higher (137.55+/-40.11
      mm(2) vs. 119.64+/-38.14 mm(2), P=0.028) in patients with medial wall fractures
      than in those with inferior wall fractures. CONCLUSIONS: Patients with fewer
      ethmoid air cell septa and a larger lamina papyracea area per septum are more
      likely to develop medial wall fractures than inferior wall fractures.

PMID- 18824730
TI  - Validation of spectral domain optical coherence tomographic Doppler shifts using
      an in vitro flow model.
AB  - PURPOSE: To validate velocity measurements produced by spectral domain optical
      coherence tomography (SD-OCT) in an in vitro laminar flow model. METHODS: A 30-mL
      syringe filled with skim milk was inserted into a syringe pump. Intravenous
      (i.v.) tubing connected the syringe within the pump to a glass capillary tube
      (internal diameter, 0.579 mm) shallowly embedded in agarose gel, then to a
      collection reservoir. SD-OCT imaging was performed with an anterior segment eye
      scanner and optics engine coupled with a 100-nm bandwidth broadband
      superluminescent diode. Scan density of 128 x 128 A-scans was spread over a 4 x 4
      mm area, and each A-scan was 2 mm in length. Fifteen sequential stationary A
      scans were obtained at each 128 x 128 position, and Doppler shifts were
      calculated from temporal changes in phase. The beam-to-flow vector Doppler angle
      was determined from three-dimensional scans. RESULTS: In all reflectance and
      Doppler images, a clear laminar flow pattern was observed, with v(max) appearing
      in the center of the flow column. Phase wrapping was observed at all measured
      flow velocities, and fringe washout progressively shattered reflectance and phase
      signals beyond the Nyquist limit. The observed percentages of the velocity
      profile at or below Nyquist frequency was highly correlated with the predicted
      percentages (R(2)=0.934; P=0.007). CONCLUSIONS: SD-OCT provides objective Doppler
      measurements of laminar fluid flow in an in vitro flow system in a range up to
      the Nyquist limit.

PMID- 18824731
TI  - Genomic aberrations and cellular heterogeneity in SV40-immortalized human corneal
      epithelial cells.
AB  - PURPOSE: Simian virus (SV)40-immortalized human corneal epithelial (HCE-T) cells
      have been widely used as an in vitro model of human corneal epithelial cells. The
      nature of this cell line was assessed for genomic aberrations and cellular
      heterogeneity. METHODS: For the quantitative measurement of genomic aberrations,
      array-based comparative genomic hybridization (CGH) analysis was performed. For
      identification of cellular heterogeneity, cell morphology, growth kinetics,
      transepithelial electrical resistance, and transfection/transcriptional
      efficiency were analyzed. Real-time PCR and chromosomal fluorescent in situ
      hybridization (cFISH) against some gained or lost loci were performed, to assess
      genomic heterogeneity. Expressed sequence tags (ESTs) for this cell line were
      collected to assess differences in the gene expression profiles between HCE-T
      cells and normal corneal epithelial cells. Southern blot analysis and inverse PCR
      analyses were used to determine the genomic integration site of the SV40 large T
      antigen gene (LTAG). RESULTS: Array CGH analysis demonstrated that the genomic
      content of HCE-T cells is different from the normal healthy genome. The results
      from cellular functional assays, real-time PCR, and cFISH strongly indicated that
      HCE-T cells consist of a significant number of heterogeneous cell populations.
      The genomic integration site of the SV40 large T antigen was at p22.1 of
      chromosome 9. CONCLUSIONS: The results indicate that HCE-T cells have an altered
      genomic content and that they are composed of heterogeneous cell populations.
      This should be considered when conducting experiments or interpreting the results
      of studies that use this cell line.

PMID- 18824732
TI  - Vernier acuity in Down syndrome.
AB  - PURPOSE: Down syndrome (DS) is associated with reduced visual performance.
      Although poor optical quality has been implicated, no previous data are available
      regarding the contribution of cortical visual processes. The present study
      investigated Vernier performance for the first time in children with DS to
      evaluate the integrity of higher visual processing in this condition. METHODS:
      Participants were 29 children aged 9 to 16 years who had DS and 68 age-matched
      developmentally normal children acting as controls. All wore best refractive
      correction, and none had clinically significant ocular abnormalities. An out-of
      phase test-pedestal Vernier stimulus was used to facilitate short test distances
      and optimize compliance with testing. RESULTS: Testing was successfully completed
      by 86% (n=25) of the DS group and 96% (n=65) of the control group. Vernier
      thresholds were invariant with age in both groups. Mean Vernier acuities were
      39.8 arc seconds (SD+/-13.3) and 14.6 arc seconds (SD+/-4.7) in DS and control
      groups, respectively. When compared with control data, mean Vernier acuity was
      reduced by a factor of 2.7 in DS. CONCLUSIONS: Vernier thresholds were
      successfully measured in children with DS and were found to be reduced,
      indicating that cortical visual function is compromised. Impairment in cortical
      function in DS may be implicit, relating to histologic reports of differences in
      the DS brain, or they may result from abnormal experience during visual
      development. The magnitude of the cortical deficit demonstrated in DS in the
      present study is significant and should be considered along with previously
      reported poor optical quality.

PMID- 18824733
TI  - Human leukocyte antigen (HLA)-B, DRB1, and DQB1 allotypes associated with disease
      and protection of trachoma endemic villagers.
AB  - PURPOSE: Trachoma remains the leading preventable infectious cause of blindness
      in developing countries. Human leukocyte antigen (HLA) associations with ocular
      disease severity and persistent Chlamydia trachomatis infection of Tanzanians
      living in trachoma-endemic villages were examined to determine possible
      protective candidate allotypes for vaccine development. METHODS: Buccal swab
      scrapes were taken from subjects in the Trichiasis Study Group (TSG), which
      studied females only, and the Family Trachoma Study (FTS), which compared
      persistently infected probands who had severe disease with disease-free siblings
      and parents. DNA was purified for polymerase chain reaction sequence-specific
      oligonucleotide identification of HLA-DRB1, DQB1, and B allotypes. Infection was
      detected from conjunctival scrapes using a C. trachomatis-specific PCR-enzyme
      immunoassay for the MOMP-1 gene. RESULTS: In the TSG, DR*B11 (odds ratio [OR],
      0.48; 95% confidence interval [CI], 0.26-0.90; P=0.02) was significantly
      associated with lack of trichiasis, whereas HLA-B*07 (OR, 3.26; 95% CI, 1.42
      7.49; P=0.004) and HLA-B*08 (OR, 5.12; 95% CI, 1.74-15.05; P=0.001) were
      associated with trichiasis. In addition, HLA-B*14 was significantly associated
      with inflammatory trachoma + follicular trachoma (OR, 3.76; 95% CI, 1.70-8.33;
      P=0.04). There were no significant allele frequencies for the FTS. CONCLUSIONS:
      The data suggest that HLA-DRB*11 may offer protection from trichiasis in trachoma
      hyperendemic villages. Complete allotype identification and designation of its
      respective protective CD4(+) T-cell antigens could provide a testable candidate
      vaccine for blindness prevention. Additionally, buccal swab DNA was sufficiently
      stable when acquired under harsh field conditions and stored long term in the
      freezer for low-resolution HLA typing.

PMID- 18824734
TI  - Ability of Stratus OCT to detect progressive retinal nerve fiber layer atrophy in
      glaucoma.
AB  - PURPOSE: To evaluate the ability of Stratus optical coherence tomography (OCT
      version 4.0; Carl Zeiss Meditec, Inc., Dublin, CA) to detect progressive
      glaucomatous retinal nerve fiber layer (RNFL) atrophy observed by red-free RNFL
      photography. METHODS: Intersession test-retest variability of each clock hour,
      quadrant, and average RNFL thickness was determined in 53 control subjects. The
      sensitivity and specificity of OCT for identification of progressive RNFL atrophy
      were tested on subjects in whom this condition was clearly observed in red-free
      RNFL photographs (n=27) and in another control group (n=62), according to
      criteria derived from test-retest variability. RESULTS: The sensitivity of
      Stratus OCT RNFL measurement ranged from 14.8% (for average RNFL thickness) to
      85.2% (for clock hour thickness) when tested at the 95% confidence level. The
      specificity of Stratus OCT RNFL measurement was approximately 95% for average
      RNFL thickness, but decreased considerably with clock hour (59.7%) and quadrant
      thickness (77.4%). This is presumably because multiple testing was used for
      multiple clock hours and quadrants. When calculated based on two consecutive
      follow-up examinations, the specificity for the clock hour measurements increased
      to 86.6% and that for quadrant thickness increased to 92.5%. The OCT-measured
      RNFL thickness change showed excellent topographic agreement with the progressive
      RNFL atrophy observed using RNFL photography. CONCLUSIONS: Within the limits of
      retest variability, Stratus OCT detects progressive RNFL atrophy with high
      sensitivity and moderate specificity in cases showing localized progressive loss
      of retinal nerve fibers in red-free photographs. The specificity can be improved
      by use of multiple measurements. Stratus OCT is a potentially useful technique
      for detection of glaucoma progression.

PMID- 18824735
TI  - Inhibitions of chloride transport and gap junction reduce fluid flow across the
      whole porcine ciliary epithelium.
AB  - PURPOSE: To study the effects of chloride transport and gap junction inhibitors
      on fluid formation across the porcine ciliary epithelium. METHODS: A complete
      annulus of porcine iris-ciliary body preparation was mounted onto a modified
      Ussing type chamber to measure the fluid flow (FF) rate. The potential difference
      (PD) across the preparation was monitored simultaneously. The effects of several
      inhibitors on chloride transport and gap junction were studied. These included
      4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), 5-(N,N
      dimethyl)amiloride hydrochloride (DMA), bumetanide, niflumic acid, and heptanol.
      RESULTS: The average baseline FF rate was 2.56 +/- 0.07 microL/h per preparation
      (n = 33). DIDS (0.1 mM) or DMA (0.1 mM) showed no effect on both FF and PD when
      added to the blood side of the preparation. Bumetanide (0.1 mM), on the blood
      side, inhibited the FF by 46% and caused a slight depolarization of PD. Heptanol
      (3.5 mM) depolarized the PD and reduced FF by 45% and 78% through the blood and
      aqueous sides, respectively. Niflumic acid (1 mM at the aqueous side) also
      depolarized the PD and significantly inhibited the FF (62%). CONCLUSIONS: The
      effects of the chloride transport inhibitors on fluid formation across the
      porcine iris-ciliary body were comparable to that in previous chloride transport
      studies. The results indicated that fluid secretion by the isolated porcine
      ciliary epithelium is mainly driven by chloride transport. However, there may be
      other unidentified ion movements that drive residual FF after chloride transport
      is inhibited.

PMID- 18824736
TI  - Three-dimensional mapping of chorioretinal vascular oxygen tension in the rat.
AB  - PURPOSE: An optical section phosphorescence lifetime imaging system was developed
      for three-dimensional mapping of oxygen tension (P(O2)) in chorioretinal
      vasculatures. METHODS: A laser line was projected at an oblique angle and scanned
      on the retina after intravenous injection of an oxygen-sensitive molecular probe
      to generate phosphorescence optical section images. An automated software
      algorithm segmented and combined images from spatially adjacent locations to
      construct depth-displaced en face retinal images. Intravascular P(O2) was
      measured by determining the phosphorescence lifetime. Three-dimensional
      chorioretinal P(O2) maps were generated in rat eyes under varying fractions of
      inspired oxygen. RESULTS: Under an air-breathing condition, mean P(O2) in the
      choroid, retinal arteries, capillaries, and veins were 58+/-2 mm Hg, 47+/-2 mm
      Hg, 44+/-2 mm Hg, and 35+/-2 mm Hg, respectively. The mean arteriovenous P(O2)
      difference was 12+/-2 mm Hg. With a lower fraction of inspired oxygen,
      chorioretinal vascular P(O2) and mean arteriovenous P(O2) differences decreased
      compared with measurements under an air-breathing condition. Retinal venous P(O2)
      was statistically lower than P(O2) measured in the retinal artery, capillaries,
      and choroid (P<0.004). CONCLUSIONS: Three-dimensional mapping of chorioretinal
      oxygen tension allowed quantitative P(O2) measurements in large retinal blood
      vessels and in retinal capillaries. This method has the potential to facilitate
      better understanding of retinal oxygenation in health and disease.

PMID- 18824737
TI  - Predictive value of a topical dexamethasone provocative test before intravitreal
      triamcinolone acetonide injection.
AB  - PURPOSE: To investigate the diagnostic value of a topical dexamethasone (DXM)
      provocative test before intravitreal triamcinolone acetonide (IVTA) injection for
      a steroid response. METHODS: Eligible patients scheduled for first-time IVTA who
      did not have glaucoma or a history of a steroid response received DXM 0.1% drops
      4 times daily over 4 weeks. After that, IVTA was given except in DXM responders
      with an IOP increase greater than 15 mm Hg. IOP was measured at baseline, 4 weeks
      after DXM treatment, at weeks 1, 2, and 4, and at months 3 and 6 after IVTA. A
      steroid response after the DXM test or after IVTA was defined as an IOP increase
      of 6 mm Hg or greater. RESULTS: Thirty-six patients (36 eyes) were analyzed. The
      DXM test had a sensitivity of 25% (95% confidence interval [CI], 0.07-0.52), a
      specificity of 100% (95% CI, 0.83-1.00), a positive predictive value of 100% (95%
      CI, 0.40-1.00), and a negative predictive value of 62% (95% CI, 0.44-0.79) for a
      steroid response after IVTA. In DXM responders, the IOP increase after IVTA was
      17.0+/-7.8 mm Hg versus 5.0+/-4.4 mm Hg in DXM nonresponders (P=0.005). The IOP
      increase after the DXM test correlated with the IOP increase after IVTA
      (P=0.001). CONCLUSIONS: The topical DXM test had a low sensitivity, a high
      specificity, a high positive predictive value, and a moderate negative predictive
      value and may be useful to predict a steroid response after IVTA. DXM responders
      demonstrated high IOP increases after IVTA, and the IOP increase after the DXM
      test correlated with the IOP increase after IVTA. If the DXM test result is
      positive, risks and benefits of IVTA should be more carefully weighted.

PMID- 18824738
TI  - Chromosomes 4q28.3 and 7q31.2 as new susceptibility loci for comitant strabismus.
AB  - PURPOSE: This study was designed to localize chromosomal susceptibility loci for
      comitant strabismus among Japanese families by genome-wide linkage analyses.
      METHODS: Fifty-five Japanese families, with at least two members with comitant
      strabismus (esotropia and/or exotropia), were subject to full ophthalmic
      examination, careful ocular history, and review of medical records. DNA was
      obtained and genotyping was performed with PCR amplification of 400
      microsatellite markers. Parametric and nonparametric linkage (NPL) analyses
      scores were calculated. Linkage analysis was performed for the whole set of
      families (55 families), and then a second analysis was performed for two
      subgroups with the phenotypes, esotropia and exotropia. RESULTS: A multipoint
      parametric heterogeneity logarithm of the odds (HLOD) score of 3.62 was obtained
      at marker D4S1575 under a dominant model, with a NPL score of 2.68 (P=0.001).
      Testing under different penetrances and disease allele frequencies revealed two
      other susceptibility loci at 7q31.2 under a recessive model (HLOD scores=3.93 and
      4.40 at 125.2 cM and 107.28 cM, respectively). Analysis of the subgroups revealed
      new susceptibility loci for esotropia; one locus at 8q24.21 is worthy of further
      investigation. CONCLUSIONS: This study suggests multiple susceptibility loci for
      comitant strabismus. The loci at chromosomes 4q28.3 and 7q31.2 show a significant
      evidence of linkage.

PMID- 18824739
TI  - Role of cPKCalpha and nPKCepsilon in EGF-stimulated goblet cell proliferation.
AB  - PURPOSE: The authors determined the role of the protein kinase C (PKC) isoforms
      cPKCalpha and nPKCepsilon in EGF-stimulated proliferation of cultured rat and
      human conjunctival goblet cells. METHODS: Rat and human conjunctivas were minced,
      and goblet cells were allowed to grow. Passage 1 cells were serum starved for 24
      to 48 hours and were incubated with the PKC inhibitors calphostin C and Go 6983
      (10(-10)-10(-7) M) for 20 minutes before stimulation with EGF (10(-7) M) for 24
      hours. The presence and localization of PKC isoforms in cultured rat goblet cells
      were determined by Western blot analysis and immunofluorescence microscopy,
      respectively. Cultured rat goblet cells were serum starved and incubated with
      adenoviruses containing genes for dominant-negative cPKCalpha (Ad DNPKCalpha,
      10(4) pfu), dominant-negative nPKCepsilon (Ad DNPKCepsilon, 10(4) pfu), and wild
      type cPKCalpha (Ad WTPKCalpha, 10(7) pfu), and proliferation was measured.
      RESULTS: In rat goblet cells, EGF-stimulated proliferation was completely
      inhibited by calphostin C, whereas Go 6983 inhibited proliferation by 53%+/-15%.
      In human goblet cells, EGF-stimulated proliferation was completely inhibited by
      calphostin C. PKCalpha, -betaI, -betaII, -delta, -epsilon, -iota/lambda, -theta, 
      gamma, and -zeta were found in cultured rat goblet cells. Ad DNPKCalpha and Ad
      DNPKCepsilon inhibited EGF-stimulated proliferation in rat goblet cells by 78%+/
      6% and 92%+/-8%, respectively. Incubation with Ad WTPKCalpha alone significantly
      increased proliferation. CONCLUSIONS: cPKCalpha and nPKCepsilon play key roles in
      conjunctival goblet cell proliferation.

PMID- 18824740
TI  - Long-term results of heart operations performed by surgeons-in-training.
AB  - BACKGROUND: We investigated the association between trainees performing
      supervised operations and late outcomes of patients undergoing cardiac surgery.
      METHODS AND RESULTS: Data were prospectively collected on patients who underwent
      coronary artery bypass graft surgery, aortic valve replacement, or a combination
      of these between 1998 and 2005 at the Maritime Heart Center, Halifax, Canada. In
      hospital mortality and a composite outcome of in-hospital mortality, stroke,
      bleeding, intra-aortic balloon pump insertion, renal failure, and sternal
      infection was compared between teaching (n=1054) and nonteaching cases (n=5877).
      Late survival and cardiovascular hospital readmissions were also examined. To
      adjust for baseline risk disparities, we used logistic regression for dichotomous
      in-hospital outcomes and Cox proportional hazards regression for survival data.
      Resident cases were significantly more likely to have high-risk features such as
      depressed ventricular function, redo operation, and urgent or emergent procedure.
      Resident as primary operator was not independently associated with in-hospital
      mortality (OR, 1.09; 95% CI, 0.75 to 1.58; P=0.66) or with the composite outcome
      (OR, 1.01; 95%, CI 0.82 to 1.26; P=0.90). The Kaplan-Meier event-free survival of
      the 2 groups was equivalent at 1, 3, and 5 years (log-rank P=0.06). By Cox
      regression, resident cases were not associated with late death or cardiovascular
      rehospitalization (hazard ratio, 1.05; 95% CI, 0.94 to 1.17; P=0.42).
      CONCLUSIONS: Cases performed by senior-level cardiac surgery residents were more
      likely to have greater acuity and complexity than staff surgeon-performed cases.
      However, clinical outcomes were similar in the short- and long-term. Allowing
      residents to perform cardiac surgery is not associated with adverse patient
      outcomes.

PMID- 18824741
TI  - Modulated inflammation by injection of high-mobility group box 1 recovers post
      infarction chronically failing heart.
AB  - BACKGROUND: Inflammation plays an important role in the progress of adverse
      ventricular remodeling after myocardial infarction. High-mobility group box 1
      (HMGB1) is a nuclear protein, which has recently been uncovered to also act as a
      modifier of inflammation when released. We hypothesized that HMGB1 injection
      could preferentially modulate local myocardial inflammation, attenuate
      ventricular remodeling, and subsequently improve cardiac performance of
      postinfarction chronic heart failure. METHODS AND RESULTS: Three weeks after left
      coronary artery ligation, HMGB1 (2.5 mug) or PBS was intramyocardially injected
      into rat hearts. At 28 days after injection, left ventricular ejection fraction
      was significantly improved after HMGB1 injection compared to PBS (39.3+/-1.4
      versus 33.3+/-1.8%; P<0.01). Accumulation of CD45(+) inflammatory cells, two
      thirds of which were OX62(+) dendritic cells, in the peri-infarct area was
      significantly attenuated by HMGB1 injection. Dramatic changes in the expression
      of major proinflammatory cytokines were not detected by microarray or RT-PCR.
      Adverse ventricular remodeling including cardiomyocyte hypertrophy (cardiomyocyte
      cross-sectional area; 439+/-7 versus 458+/-6 mum(2); P<0.05) and extracellular
      collagen deposition (collagen volume fraction; 11.9+/-0.4 versus 15.2+/-0.6%;
      P<0.01) was attenuated by HMGB1 injection. Analyses of signal transduction
      pathways revealed that HMGB1 injection activated ERK1/2, but not p38, Akt, and
      Smad3. Cardiac regeneration and neovascularization were not observed.
      CONCLUSIONS: HMGB1 injection modulated the local inflammation in the
      postinfarction chronically failing myocardium, particularly via reducing the
      accumulation of dendritic cells. This modulated inflammation resulted in
      attenuated fibrosis and cardiomyocyte hypertrophy, which thereby improved global
      cardiac function. These data suggest that HMGB1 may be valuable for the chronic
      heart failure treatment.

PMID- 18824742
TI  - Minimally invasive epicardial injections using a novel semiautonomous robotic
      device.
AB  - BACKGROUND: We have developed a novel miniature robotic device (HeartLander) that
      can navigate on the surface of the beating heart through a subxiphoid approach.
      This study investigates the ability of HeartLander to perform in vivo
      semiautonomous epicardial injections on the beating heart. METHODS AND RESULTS:
      The inchworm-like locomotion of HeartLander is generated using vacuum pressure
      for prehension of the epicardium and drive wires for actuation. The control
      system enables semiautonomous target acquisition by combining the joystick input
      with real-time 3-dimensional localization of the robot provided by an
      electromagnetic tracking system. In 12 porcine preparations, the device was
      inserted into the intrapericardial space through a subxiphoid approach.
      Ventricular epicardial injections of dye were performed with a custom injection
      system through HeartLander's working channel. HeartLander successfully navigated
      to designated targets located around the circumference of the ventricles (mean
      path length=51+/-25 mm; mean speed=38+/-26 mm/min). Injections were successfully
      accomplished following the precise acquisition of target patterns on the left
      ventricle (mean injection depth=3.0+/-0.5 mm). Semiautonomous target acquisition
      was achieved within 1.0+/-0.9 mm relative to the reference frame of the tracking
      system. No fatal arrhythmia or bleeding was noted. There were no histological
      injuries to the heart due to the robot prehension, locomotion, or injection.
      CONCLUSIONS: In this proof-of-concept study, HeartLander demonstrated
      semiautonomous, precise, and safe target acquisition and epicardial injection on
      a beating porcine heart through a subxiphoid approach. This technique may
      facilitate minimally invasive cardiac cell transplantation or polymer therapy in
      patients with heart failure.

PMID- 18824743
TI  - Comparison of different adult stem cell types for treatment of myocardial
      ischemia.
AB  - BACKGROUND: A comparative analysis of the efficacy of different cell candidates
      for the treatment of heart disease remains to be described. This study is
      designed to evaluate the therapeutic efficacy of 4 cell types in a murine model
      of myocardial infarction. METHODS AND RESULTS: Bone marrow mononuclear cells
      (MN), mesenchymal stem cells (MSC), skeletal myoblasts (SkMb), and fibroblasts
      (Fibro) expressing firefly luciferase (Fluc) and green fluorescence protein (GFP)
      were characterized by flow cytometry, bioluminescence imaging (BLI), and
      luminometry. Female FVB mice (n=70) underwent LAD ligation and intramyocardially
      received one cell type (5x10(5)) or PBS. Cell survival was measured by BLI and by
      TaqMan PCR. Cardiac function was assessed by echocardiography and invasive
      hemodynamic measurements. Fluc expression correlated with cell number in all
      groups (r(2)>0.93). In vivo BLI revealed acute donor cell death of MSC, SkMb, and
      Fibro within 3 weeks after transplantation. By contrast, cardiac signals were
      still present after 6 weeks in the MN group, as confirmed by TaqMan PCR (P<0.01).
      Echocardiography showed significant preservation of fractional shortening in the
      MN group compared to controls (P<0.05). Measurements of left ventricular end
      systolic/diastolic volumes revealed that the least amount of ventricular
      dilatation occurred in the MN group (P<0.05). Histology confirmed the presence of
      MN, although there was no evidence of transdifferentiation by donor MN into
      cardiomyocytes. CONCLUSIONS: This is the first study to show that compared to
      MSC, SkMB, and Fibro, MN exhibit a more favorable survival pattern, which
      translates into a more robust preservation of cardiac function.

PMID- 18824744
TI  - Skeletal myoblasts preserve remote matrix architecture and global function when
      implanted early or late after coronary ligation into infarcted or remote
      myocardium.
AB  - BACKGROUND: The inability of skeletal myoblasts to transdifferentiate into
      cardiomyocytes suggests that their beneficial effects on cardiac function after a
      myocardial infarction are mediated by paracrine effects. We evaluated the roles
      of these factors in the preservation of matrix architecture (in the infarct and
      remote regions) by varying the timing (postmyocardial infarction) and delivery
      site of the implanted cells. METHODS AND RESULTS: Skeletal myoblasts (5x10(6)) or
      control media were injected into the infarct or noninfarcted myocardium at 5 or
      30 days after coronary artery ligation in rats. Function was assessed by
      echocardiography before transplantation and 14 and 30 days thereafter and with a
      Millar catheter at 30 days after transplantation. Ventricular geometry, remote
      fibrillar collagen architecture, and changes in the matrix metalloproteinase-TIMP
      system were evaluated. Myoblast implantation in both sites and at both times
      preserved matrix architecture (length and width of collagen fibers) in the remote
      myocardium (in association with some decreases in remote myocardial matrix
      metalloprotease activity), improved global cardiac function, and attenuated the
      progressive increase in end diastolic volume (P<0.05 for all measures compared
      with medium controls). Cells delivered into the infarct region preserved scar
      thickness; cells delivered into the noninfarcted myocardium preserved wall
      thickness. CONCLUSIONS: Regardless of whether the cells were injected into the
      infarct or the noninfarcted myocardium early after an myocardial infarction or
      later, skeletal myoblasts improved cardiac function by preventing ventricular
      dilation and preserving matrix architecture in the remote region, likely mediated
      by paracrine effects.

PMID- 18824745
TI  - A factor underlying late-phase arrhythmogenicity after cell therapy to the heart:
      global downregulation of connexin43 in the host myocardium after skeletal
      myoblast transplantation.
AB  - BACKGROUND: Arrhythmia occurrence is a variable but serious concern of cell
      therapy for treating heart failure. Using a rat postinfarction chronic heart
      failure model, we compared skeletal myoblast (SMB) with bone marrow cell (BMC)
      injection to highlight donor cell-specific, late-phase arrhythmogenesis and the
      underlying factors. METHODS AND RESULTS: SMBs or BMCs derived from male GFP
      transgenic rats, or PBS were injected intramyocardially into female rat hearts 3
      weeks after coronary artery occlusion. At 28 days after injection,
      echocardiography showed that the left ventricular ejection fraction was
      significantly improved in both the SMB and BMC groups, compared to PBS control
      despite poor graft survival as assessed by PCR for the male-specific gene. Radio
      telemetry analysis revealed that the SMB group displayed a higher occurrence of
      ventricular premature contractions with an elongation of the QRS complex and the
      hearts were more susceptible to isopreterenol-induced ventricular tachycardia
      compared to the BMC and PBS groups. Western blot and immunoconfocal analysis
      showed that the gap junction protein, connexin43, was widely and persistently
      decreased in the SMB group compared to the other groups. IL-1beta was shown to be
      upregulated in hearts after SMB injection, and in vitro experiments demonstrated
      that exposure to IL-1beta caused a decrease in connexin43 and intercellular
      communication in cultured cardiomyocytes. CONCLUSIONS: Although cell therapy was
      capable of improving function of the postinfarction chronically failing heart,
      there was late-phase arrhythmogenicity specific to donor cell type. Global
      downregulation of connexin43 in the host myocardium was indicated to be an
      important factor underlying late-phase arrhythmogenicity after SMB
      transplantation.

PMID- 18824746
TI  - Endothelial cell coculture within tissue-engineered cardiomyocyte sheets enhances
      neovascularization and improves cardiac function of ischemic hearts.
AB  - BACKGROUND: Regenerative therapies, including myocardial tissue engineering, have
      been pursued as a new possibility to repair the damaged myocardium, and
      previously the transplantation of layered cardiomyocyte sheets has been shown to
      be able to improve cardiac function after myocardial infarction. We examined the
      effects of promoting neovascularization by controlling the densities of
      cocultured endothelial cells (ECs) within engineered myocardial tissues created
      using our cell sheet-based tissue engineering approach. METHODS AND RESULTS:
      Neonatal rat cardiomyocytes were cocultured with GFP-positive rat-derived ECs on
      temperature-responsive culture dishes. Cocultured ECs formed cell networks within
      the cardiomyocyte sheets, which were preserved during cell harvest from the
      dishes using simple temperature reduction. We also observed significantly
      increased in vitro production of vessel-forming cytokines by the EC-positive
      cardiac cell sheets. After layering of 3 cardiac cell sheets to create 3
      dimensional myocardial tissues, these patch-like tissue grafts were transplanted
      onto infarcted rat hearts. Four weeks after transplantation, recovery of cardiac
      function could be significantly improved by increasing the EC densities within
      the engineered myocardial tissues. Additionally, when the EC-positive cardiac
      tissues were transplanted to myocardial infarction models, we observed
      significantly greater numbers of capillaries in the grafts as compared with the
      EC-negative cell sheets. Finally, blood vessels originating from the engineered
      EC-positive cardiac tissues bridged into the infarcted myocardium to connect with
      capillaries of the host heart. CONCLUSIONS: In vitro engineering of 3-dimensional
      cardiac tissues with preformed EC networks that can be easily connected to host
      vessels can contribute to the reconstruction of myocardial tissue grafts with a
      high potential for cardiac function repair. These results indicate that
      neovascularization can contribute to improved cardiac function after the
      transplantation of engineered cardiac tissues.

PMID- 18824747
TI  - Risk model of thoracic aortic surgery in 4707 cases from a nationwide single-race
      population through a web-based data entry system: the first report of 30-day and
      30-day operative outcome risk models for thoracic aortic surgery.
AB  - BACKGROUND: The objective of this study was to collect integrated data from
      nationwide hospitals using a web-based national database system to build up our
      own risk model for the outcome from thoracic aortic surgery. METHODS AND RESULTS:
      The Japan Adult Cardiovascular Surgery Database was used; this involved
      approximately 180 hospitals throughout Japan through a web-based data entry
      system. Variables and definitions are almost identical to the STS National
      Database. After data cleanup, 4707 records were analyzed from 97 hospitals
      (between January 1, 2000, and December 31, 2005). Mean age was 66.5 years.
      Preoperatively, the incidence of chronic lung disease was 11%, renal failure was
      9%, and rupture or malperfusion was 10%. The incidence of the location along the
      aorta requiring replacement surgery (including overlapping areas) was: aortic
      root, 10%; ascending aorta, 47%; aortic arch, 44%; distal arch, 21%; descending
      aorta, 27%; and thoracoabdominal aorta, 8%. Raw 30-day and 30-day operative
      mortality rates were 6.7% and 8.6%, respectively. Postoperative incidence of
      permanent stroke was 6.1%, and renal failure requiring dialysis was 6.7%. OR for
      30-day operative mortality was as follows: emergency or salvage, 3.7; creatinine
      >3.0 mg/dL, 3.0; and unexpected coronary artery bypass graft, 2.6. As a
      performance metric of the risk model, C-index of 30-day and 30-day operative
      mortality was 0.79 and 0.78, respectively. CONCLUSIONS: This is the first report
      of risk stratification on thoracic aortic surgery using a nationwide surgical
      database. Although condition of these patients undergoing thoracic aortic surgery
      was much more serious than other procedures, the result of this series was
      excellent.

PMID- 18824748
TI  - Dynamic changes in matrix metalloprotienase activity within the human myocardial
      interstitium during myocardial arrest and reperfusion.
AB  - BACKGROUND: Past studies have clearly established that matrix metalloproteinases
      (MMPs) contribute to adverse myocardial remodeling with ischemia and reperfusion.
      However, these studies measured MMP levels in extracted samples, and therefore
      whether and to what degree actual changes in interstitial MMP activity occur
      within the human myocardium in the context of ischemia/reperfusion remained
      unknown. METHODS AND RESULTS: The present study directly quantified MMP
      interstitial activity within the myocardium of patients (n=14) undergoing
      elective cardiac surgery during steady-state conditions, as well as during and
      following an obligatory period of myocardial arrest and reperfusion achieved by
      cardiopulmonary bypass. Interstitial MMP activity was continuously monitored
      using a validated MMP fluorogenic substrate, a microdialysis system placed within
      the myocardium, and in-line fluorescent detection system. MMP activity, as
      measured by fluorescent emission, reached a stable steady state level by 10
      minutes after deployment of the microdialysis system. During initiation of
      cardiopulmonary bypass, MMP activity increased by 20% from baseline values
      (P<0.05), and then rapidly fell with cardiac arrest and longer periods of
      cardiopulmonary bypass. However, with restoration of myocardial blood flow and
      separation from cardiopulmonary bypass, MMP interstitial activity increased by
      over 30% from baseline (P<0.05). CONCLUSIONS: The present study directly
      demonstrated that MMP proteolytic activity exists within the human myocardial
      interstitium and is a dynamic process under conditions such as myocardial arrest
      and reperfusion.

PMID- 18824749
TI  - Ascending and transverse aortic arch repair: the impact of retrograde cerebral
      perfusion.
AB  - BACKGROUND: The benefit of retrograde cerebral perfusion (RCP) with profound
      hypothermic circulatory arrest has been subject to much debate. We examined our
      experience with ascending and transverse arch repairs to determine the impact of
      retrograde cerebral perfusion on stroke and mortality. METHODS AND RESULTS:
      Between August 1991 and June 2007, we performed 1107 repairs of the ascending and
      transverse aortic arch. RCP was used in 82% of cases (907 of 1107). Sixty-two
      percent were men (682 of 1107); median age was 64 years (range, 16 to 93 years).
      Perioperative variables were evaluated using univariate and multivariable
      analysis for mortality and stroke. Thiry-day mortality was 10.4% (115 of 1107).
      Stroke occurred in 2.8% (31 of 1107) of patients. Univariate risk factors for
      mortality were increasing age (P<0.0001), history of coronary artery disease
      (P=0.02), previous coronary artery bypass (P=0.02), emergency status (P<0.0001),
      acute dissection (P=0.02), rupture (P=0.0001), preoperative glomerular filtration
      rate, bypass time (P<0.0001), crossclamp time (P<0.007), RCP time (P<0.0001), and
      packed red blood cell transfusions (P=0.0001). Univariate risk factors for stroke
      included emergency status (P<0.02), cerebrovascular disease (P<0.02), and
      crossclamp time (P<0.04). Independent risk factors for mortality were glomerular
      filtration rate <90 mL/min (P=0.0004), emergency status (P=0.006), rupture
      (P=0.004), cardiopulmonary bypass time >120 minutes (P<0.04), and packed red
      blood cell transfusions (P=0.0002). Risk factors for stroke were emergency status
      (P<0.009) and hypertension (P<0.05). RCP was protective against mortality and
      stroke. CONCLUSIONS: The use of RCP with profound hypothermic circulatory arrest
      was associated with a reduction in mortality and stroke. The use of RCP remains
      warranted during repairs of the ascending and transverse aortic arch.

PMID- 18824750
TI  - Tight heart rate control reduces secondary adverse events in patients with type B
      acute aortic dissection.
AB  - BACKGROUND: Although type B aortic dissection has been treated with beta blockers
      to lower the arterial blood pressure (BP), there has been little evidences about
      reduction in heart rate (HR). We assessed whether tight HR control improved the
      outcome of medical treatment in patients with aortic dissection. METHODS AND
      RESULTS: From 1997 to 2005, 171 patients with acute aortic dissection medically
      treated and controlled to lower BP under 120 mm Hg were enrolled. Based on the
      average HR at 3, 5, and 7 days after the onset, patients were divided into tight
      HR (<60 beat per minute) control group (32 patients; mean HR of 56.6+/-3.1 beat
      per minute) and conventional HR (>/=60 beat per minute) control group (139
      patients; mean HR of 71.7+/-8.2 beat per minute). We compared the frequency of
      aortic events including late organ or limb ischemia, aortic rupture, recurrent
      dissection, and aortic expansion of >5 mm, and surgical requirement between two
      groups. During a median follow-up of 27.0 months, late organ or limb ischemia,
      aortic rupture, recurrent dissection, pathological aortic expansion, and aortic
      surgery occurred in 0, 8, 14, 39, and 26 patients, respectively. Reduction in
      aortic events was observed in tight HR control group (12.5%) compared to
      conventional HR control group (36.0%), (Odds ratio: 0.25, C.I.: 0.08 to 0.77,
      P<0.01). CONCLUSIONS: The present study demonstrated that tight heart rate
      control improved the outcome of medical treatment in patients with aortic
      dissection.

PMID- 18824751
TI  - Factors associated with prolonged recovery after the fontan operation.
AB  - BACKGROUND: Mortality and major morbidity after the Fontan operation is low in
      the current era. However, factors contributing to prolonged postoperative
      recovery are not clearly understood. METHODS AND RESULTS: Data on all patients
      admitted to the cardiac intensive care unit (CICU) after a Fontan operation
      between June 2001 and December 2005 were retrospectively analyzed. We excluded
      all patients who died, required Fontan takedown, or required ECMO. The study
      cohort was further divided into a prolonged recovery group that included patients
      with >75%ile for duration of mechanical ventilation or pleural drainage, and a
      standard recovery group which included all other patients. A multivariable
      logistic regression model was used to compare demographic, anatomic, and
      physiological variables between the prolonged and standard recovery groups. There
      were 226 Fontan operations performed. Of the study population (n=218), the median
      age was 2.61 years (1.0 to 31.9 years) and weight was 12.45 kg (8.4 to 77.5 kg).
      The most common diagnosis was hypoplastic left heart syndrome (n=80, 36.7%). A
      systemic right atrioventricular valve was present in 139 (63.7%). The lateral
      tunnel fenestrated Fontan was the most common surgery (n=195, 89.4%). Within the
      study population, 81 (38%) patients meet criteria for prolonged recovery.
      Univariate risk factors for prolonged recovery included higher preoperative PVR
      (P=0.033), longer bypass times (P=0.009), higher postbypass lactate level
      (P=0.017), higher postoperative central venous (P<0.001) common atrial pressure
      (P=0.042), inotropic score (P<0.001), and need for greater volume resuscitation
      during the 24 postoperative hours (>75% for the entire group; P<0.001). In a
      multivariable model, need for greater volume resuscitation (OR 2.81, 95% CI 1.30,
      6.05) was the only independent risk factor for prolonged outcome after the Fontan
      operation. CONCLUSIONS: High volume expansion in the early postoperative period
      is an independent risk factor for prolonged recovery. The need for high volume
      expansion may represent the compound effects of multiple risk factors including
      preoperative hemodynamics and a marked systemic inflammatory response to surgery
      and cardiopulmonary bypass, which in turn may mediate prolonged recovery.

PMID- 18824752
TI  - Performance of cavopulmonary palliation at elevated altitude: midterm outcomes
      and risk factors for failure.
AB  - BACKGROUND: Outcomes of patients undergoing cavopulmonary palliation for single
      ventricle physiology may be impacted by living at altitude, as the passive
      pulmonary circulation is dependent on the resistance of the pulmonary vascular
      bed. The objective of this study is to identify risk factors for failure of
      cavopulmonary palliation at elevated altitude. METHODS AND RESULTS: Between
      January 1995 and March 2007, 122 consecutive patients living at a mean altitude
      of 1600 m (range 305 to 2570) underwent a bidirectional Glenn (BDG). There was
      one in-hospital mortality and 7 late deaths. 52 have proceeded to the Fontan
      procedure. Survival after BDG was 92.4% at 5 years. Freedom from palliation
      failure, defined as death, transplant, BDG/Fontan takedown, or revision was 81%
      at 5 years. At a mean follow-up of 39.8 months, 90 patients (75%) were in New
      York Heart Association class I. Patients with failing cavopulmonary circulation
      had higher pre-BDG pulmonary artery pressure (PAP) (18.3+/-6.1 mm Hg versus
      14.8+/-5.1 mm Hg, P=0.016) and higher pre-BDG transpulmonary gradient (TPG)
      (11.2+/-6.2 mm Hg versus 7.7+/-4.3 mm Hg, P=0.014). Post-BDG, patients with
      palliation failure had increased PAP (15.0+/-5.7 mm Hg versus 10.8+/-2.8 mm Hg,
      P=0.008) and indexed pulmonary vascular resistance (PVRI) (2.43+/-1.0 Wood U .
      m(2) versus 1.52+/-0.9 Wood U . m(2), P=0.007). CONCLUSIONS: The majority of
      patients at moderate altitude have favorable outcomes after BDG or Fontan
      palliation. Risk factors for palliation failure at elevated altitude include PAP
      >15 mm Hg, TPG >8 mm Hg, and PVRI >2.5 Wood U . m(2).

PMID- 18824753
TI  - Biventricular response after pulmonary valve replacement for right ventricular
      outflow tract dysfunction: is age a predictor of outcome?
AB  - BACKGROUND: The timing of pulmonary valve replacement (PVR) for free pulmonary
      incompetence in patients with congenital heart disease remains a dilemma for
      clinicians. We wanted to assess the determinants of improvement after PVR for
      pulmonary regurgitation over a wide range of patient ages and to use any
      identified predictors to compare clinical outcomes between patient groups.
      METHODS AND RESULTS: Seventy-one patients (mean age 22+/-11 years; range, 8.5 to
      64.9; 72% tetralogy of Fallot) underwent PVR for severe pulmonary regurgitation.
      New York Heart Association class improved after PVR (median of 2 to 1, P<0.0001).
      MRI and cardiopulmonary exercise testing were performed before and 1 year after
      intervention. After PVR, there was a significant reduction in right ventricular
      volumes (end diastolic volume 142+/-43 to 91+/-18, end systolic volume 73+/-33 to
      43+/-14 mL/m(2), P<0.0001), whereas left ventricular end diastolic volume
      increased (66+/-12 to 73+/-13 mL/m(2), P<0.0001). Effective cardiac output
      significantly increased (right ventricular: 3.0+/-0.8 to 3.3+/-0.8 L/min, P=0.013
      and left ventricular: 3.0+/-0.6 to 3.4+/-0.7 L/min, P<0.0001). On cardiopulmonary
      exercise testing, ventilatory response to carbon dioxide production at anaerobic
      threshold improved from 35.9+/-5.8 to 34.1+/-6.2 (P=0.008). Normalization of
      ventilatory response to carbon dioxide production was most likely to occur when
      PVR was performed at an age younger than 17.5 years (P=0.013). CONCLUSIONS: A
      relatively aggressive PVR policy (end diastolic volume <150 mL/m(2)) leads to
      normalization of right ventricular volumes, improvement in biventricular
      function, and submaximal exercise capacity. Normalization of ventilatory response
      to carbon dioxide production is most likely to occur when surgery is performed at
      an age </=17.5 years. This is also associated with a better left ventricular
      filling and systolic function after surgery.

PMID- 18824754
TI  - Ventricular-vascular stiffening in patients with repaired coarctation of aorta:
      integrated pathophysiology of hypertension.
AB  - BACKGROUND: Despite successful repair, patients with coarctation of the aorta
      (COA) often show persistent hypertension at rest and/or during exercise. Previous
      studies indicated that the hypertension is mainly due to abnormalities in the
      arterial bed and its regulatory systems. We hypothesized that ventricular
      systolic stiffness also contributes to the hypertensive state in these patients
      in addition to increased vascular stiffness. METHODS AND RESULTS: The study
      involved 43 patients with successfully repaired COA and 45 age-matched control
      subjects. Ventricular systolic stiffness (end systolic elastance) and arterial
      stiffness (effective arterial elastance) were measured invasively by ventricular
      pressure-area relationship during varying preload before and after beta
      adrenergic stimulation. The mean systolic blood pressure was significantly higher
      with concomitant increases in both end systolic elastance and effective arterial
      elastance in patients with COA compared with control subjects (113.2+/-16.8
      versus 91.0+/-9.1 mm Hg, 44.5+/-17.0 versus 19.2+/-6.7 mm Hg/mL/m(2), and 27.8+/
      11.4 versus 20.2+/-4.8 mm Hg/mL/m(2), respectively; P<0.01 for each). End
      systolic elastance and effective arterial elastance of patients with COA showed
      exaggerated responses to beta-adrenergic stimulation, further amplifying blood
      pressure elevation. Quantification analyses assuming that ventricular systolic
      stiffness of patients with COA is equal to that of the control revealed that
      ventricular systolic stiffness accounts for approximately 50% to 70% of the
      elevated blood pressure in patients with COA. Furthermore, combined ventricular
      arterial stiffening amplified systolic pressure sensitivity to increased preload
      during abdominal compression and limited stroke volume gain/relaxation
      improvement induced by beta-adrenergic stimulation. CONCLUSIONS: Increased
      ventricular systolic stiffness, coupled with increased arterial stiffness, plays
      important roles in hypertension in patients with repaired COA. Thus, ventricular
      systolic stiffness is a potentially suitable target for reduction of blood
      pressure and improvement of prognosis of patients with COA.

PMID- 18824755
TI  - Long-term outcomes of coronary-artery bypass graft surgery versus percutaneous
      coronary intervention for multivessel coronary artery disease in the bare-metal
      stent era.
AB  - BACKGROUND: Observational registries comparing coronary artery bypass graft
      (CABG) surgery and percutaneous coronary intervention (PCI) have reported long
      term survival results that are discordant with those of randomized trials.
      METHODS AND RESULTS: We conducted a multicenter study in Japan enrolling
      consecutive patients undergoing first CABG or PCI between January 2000 and
      December 2002. Among 9877 patients enrolled, 5420 (PCI: 3712, CABG: 1708) had
      multivessel disease without left main involvement. Because age is an important
      determinant when choosing revascularization strategies, survival analysis was
      stratified by either age >/=75 or <75 years. Analyses were also performed in
      other relevant subgroups. Median follow-up interval was 1284 days with 95% follow
      up rate at 2 years. At 3 years, unadjusted survival rates were 91.7% and 89.6% in
      the CABG and PCI groups, respectively (log rank P=0.26). After adjustment for
      baseline characteristics, survival outcome tended to be better after CABG (hazard
      ratio for death after PCI versus CABG [HR], 95% confidence interval [CI]: 1.23
      [0.99-1.53], P=0.06). Adjusted survival outcomes also tended to be better for
      CABG among elderly patients (HR [95%CI]: 1.37 [0.98-1.92] P=0.07), but not among
      nonelderly patients (HR [95% CI]: 1.09 [0.82-1.46], P=0.55). Unadjusted and
      adjusted survival outcome for CABG and PCI were not significantly different in
      any subgroups when elderly patients were excluded from analysis. CONCLUSIONS: In
      the CREDO-Kyoto registry, survival outcomes among patients <75 years of age were
      similar after PCI and CABG, a result that is consistent with those of randomized
      trials.

PMID- 18824756
TI  - Does location of the second internal thoracic artery graft influence outcome of
      coronary artery bypass grafting?
AB  - BACKGROUND: We sought to determine whether location of the second internal
      thoracic artery (ITA) graft used for bilateral ITA grafting affects mortality and
      morbidity of patients with 3-system coronary artery disease and to identify
      factors associated with second ITA location. METHODS AND RESULTS: From January
      1972 to June 2006, 3611 patients with 3-system coronary artery disease underwent
      bilateral ITA grafting with one graft anastomosed to the left anterior descending
      system and the second to either the circumflex (n=2926) or right coronary artery
      (n=685) system. Follow-up was 9.2+/-7.2 years. Propensity score methodology was
      used to obtain risk-adjusted outcome comparisons between patients with the second
      ITA to circumflex versus right coronary artery. Hospital mortality (0.34% versus
      0.58%; P=0.4), stroke (0.96% versus 0.88%; P=0.8), myocardial infarction (1.3%
      versus 0.73%; P=0.2), renal failure (0.44% versus 0.29%; P=0.6), respiratory
      insufficiency (3.5% versus 3.8%; P=0.7), and reoperation for bleeding (3.4%
      versus 3.2%; P=0.8) were similar in patients who received the second ITA to
      circumflex or right coronary artery and remained similar after propensity score
      adjustment. Late survival (86% versus 87% at 10 years) was also similar. Despite
      this, there was a gradual decline in ITA to right coronary artery grafting.
      CONCLUSIONS: Contrary to prevailing wisdom that the second ITA graft should be
      anastomosed to the next most important left-sided coronary artery in 3-system
      coronary artery disease, it may be placed to either the circumflex or right
      coronary artery system with similar early and late outcomes.

PMID- 18824757
TI  - Comparison of bilateral internal thoracic artery revascularization using in situ
      or Y graft configurations: a prospective randomized clinical, functional, and
      angiographic midterm evaluation.
AB  - BACKGROUND: Bilateral internal thoracic arteries (BITA) demonstrated superiority
      over other grafts to the left coronary system in terms of patency and survival
      benefit. Several BITA configurations are proposed for left-sided myocardial
      revascularization, but the ideal BITA assemblage is still unidentified. METHODS
      AND RESULTS: From 03/2003 to 08/2006, 1297 consecutive patients underwent
      isolated bypass surgery in our institution. 481 patients met the inclusion
      criteria for randomization, and 304 (64%) were randomized. Patients were
      allocated to BITA in situ grafting (n=147) or Y configuration (n=152) then
      evaluated for clinical, functional, and angiographic outcome after 6 months and 3
      years. Patient telephone interviews were conducted every 3 months and a stress
      test performed twice yearly under the referring cardiologist's supervision.
      Angiographic follow-up was performed 6 months after surgery. The primary and
      secondary end points were, respectively, major adverse cerebrocardiovascular
      events (MACCE) and the proportion of ITA grafts that were completely occluded at
      follow-up angiography. More arterial anastomoses were performed in patients
      randomized to the Y than the in situ configuration (3.2 versus 2.4; P<0.001). No
      significant difference between the 2 groups in terms of hospital mortality or
      morbidity was found. At follow-up, there was no significant difference in any
      MACCE rate between the 2 groups. 450 out of 464 anastomosis (97%) in the BITA Y
      group and 287 of 295 (97%) in the BITA in situ group were controlled patent
      (P=0.99). CONCLUSIONS: Excellent patency rates were achieved using both BITA
      configurations with no significant differences in terms of MACCE up to 19 months
      postoperatively, but longer-term results remain to be established.

PMID- 18824758
TI  - The impact of diabetic status on coronary artery bypass graft patency: insights
      from the radial artery patency study.
AB  - BACKGROUND: Despite worse outcomes in diabetics after coronary artery bypass
      grafting surgery, studies have not examined graft patency in this high-risk
      group. This study examined the impact of diabetes on graft patency, 1-year
      postcoronary artery bypass grafting, using data from a multicenter randomized
      trial. METHODS AND RESULTS: The Radial Artery Patency Study enrolled 561 patients
      undergoing coronary artery bypass grafting, comparing graft patency of the
      saphenous vein (SV) versus radial artery 1-year postcoronary artery bypass
      grafting. Angiographic follow-up was acquired for 440 patients (115 diabetics,
      325 nondiabetics), each with a study radial artery and a control SV graft.
      Preoperative characteristics were similar. The proportion of small-sized target
      vessels was greater in diabetics (P=0.04). At 1 year, 33 of 230 study grafts
      (14.4%) were occluded in the diabetics versus 63 of 650 (9.7%) in the
      nondiabetics (P=0.052). Multivariable regression found diabetes to be a
      significant independent predictor of 1-year graft occlusion (relative risk, 1.45;
      95% CI, 1.03 to 2.05; P=0.03) along with female gender, SV conduit, and small
      target-vessel size. A significantly higher proportion of SV grafts were occluded
      in the diabetics (19% versus 12%, P=0.04). Radial artery grafting was protective
      in the diabetic cohort (radial artery: 11 of 115 occluded [9.5%] versus SV: 22 of
      115 occluded [19.1%], McNemar corrected P=0.05; relative risk, 0.42; 95% CI, 0.16
      to 1.01) and nondiabetics (radial artery: 25 of 325 occluded [7.7%] versus SV: 38
      of 325 occluded [11.7%], McNemar corrected P=0.11; relative risk, 0.63; 95% CI,
      0.35 to 1.10). CONCLUSIONS: Coronary artery bypass grafting occlusions were more
      common among diabetics versus nondiabetics at 1-year angiography, mainly because
      of more frequent SV graft failure in diabetics. Radial artery, compared with SV
      grafting, is protective in both diabetic and nondiabetic patients.

PMID- 18824759
TI  - Short hairpin RNA interference therapy for ischemic heart disease.
AB  - BACKGROUND: During hypoxia, upregulation of hypoxia inducible factor-1 alpha
      transcriptional factor can activate several downstream angiogenic genes. However,
      hypoxia inducible factor-1 alpha is naturally degraded by prolyl hydroxylase-2
      (PHD2) protein. Here we hypothesize that short hairpin RNA (shRNA) interference
      therapy targeting PHD2 can be used for treatment of myocardial ischemia and this
      process can be followed noninvasively by molecular imaging. METHODS AND RESULTS:
      PHD2 was cloned from mouse embryonic stem cells by comparing the homolog gene in
      human and rat. The best candidate shRNA sequence for inhibiting PHD2 was inserted
      into the pSuper vector driven by the H1 promoter followed by a separate hypoxia
      response element-incorporated promoter driving a firefly luciferase reporter
      gene. This construct was used to transfect mouse C2C12 myoblast cell line for in
      vitro confirmation. Compared with the control short hairpin scramble (shScramble)
      as control, inhibition of PHD2 increased levels of hypoxia inducible factor-1
      alpha protein and several downstream angiogenic genes by >30% (P<0.01).
      Afterward, shRNA targeting PHD2 (shPHD2) plasmid was injected intramyocardially
      following ligation of left anterior descending artery in mice. Animals were
      randomized into shPHD2 experimental group (n=25) versus shScramble control group
      (n=20). Bioluminescence imaging detected plasmid-mediated transgene expression
      for 4 to 5 weeks. Echocardiography showed the shPHD2 group had improved
      fractional shortening compared with the shScramble group at Week 4 (33.7%+/-1.9%
      versus 28.4%+/-2.8%; P<0.05). Postmortem analysis showed increased presence of
      small capillaries and venules in the infarcted zones by CD31 staining. Finally,
      Western blot analysis of explanted hearts also confirmed that animals treated
      with shPHD2 had significantly higher levels of hypoxia inducible factor-1 alpha
      protein. CONCLUSIONS: This is the first study to image the biological role of
      shRNA therapy for improving cardiac function. Inhibition of PHD2 by shRNA led to
      significant improvement in angiogenesis and contractility by in vitro and in vivo
      experiments. With further validation, the combination of shRNA therapy and
      molecular imaging can be used to track novel cardiovascular gene therapy
      applications in the future.

PMID- 18824760
TI  - Predictors of outcomes in low-flow, low-gradient aortic stenosis: results of the
      multicenter TOPAS Study.
AB  - BACKGROUND: Patients with low-flow, low-gradient aortic stenosis have a poor
      prognosis with conservative therapy but a high operative mortality if treated
      surgically. Recently, we proposed a new index of aortic stenosis severity derived
      from dobutamine stress echocardiography, the projected aortic valve area at a
      normal transvalvular flow rate, as superior to other conventional indices to
      differentiate true-severe from pseudosevere aortic stenosis. The objective of
      this study was to identify the determinants of survival, functional status, and
      change in left ventricular ejection fraction during follow-up of patients with
      low-flow, low-gradient aortic stenosis. METHODS AND RESULTS: One hundred one
      patients with low-flow, low-gradient aortic stenosis (aortic valve area </=1.2
      cm(2), left ventricular ejection fraction </=40%, and mean gradient </=40 mm Hg)
      underwent dobutamine stress echocardiography and an assessment of functional
      capacity using the Duke Activity Status Index. A subset of 72 patients also
      underwent a 6-minute walk test. Overall survival was 70+/-5% at 1 year and 57+/
      6% at 3 years. After adjusting for age, gender, and the type of treatment (aortic
      valve replacement versus no aortic valve replacement), significant predictors of
      mortality during follow-up were a Duke Activity Status Index </=20 (P=0.0005) or
      6-minute walk test distance </=320 m (P<0.0001, in the subset of 72 patients),
      projected aortic valve area at a normal transvalvular flow rate </=1.2 cm(2)
      (P=0.03), and peak dobutamine stress echocardiography left ventricular ejection
      fraction </=35% (P=0.03). More severe stenosis, defined as projected aortic valve
      area </=1.2 cm(2), was a predictor of mortality only in the no aortic valve
      replacement group. The Duke Activity Status Index, 6-minute walk test, and left
      ventricular ejection fraction improved significantly during follow-up in the
      aortic valve replacement group, but remained unchanged or decreased in the no
      aortic valve replacement group. CONCLUSIONS: In patients with low-flow, low
      gradient aortic stenosis, the most significant risk factors for poor outcome were
      (1) impaired functional capacity as measured by Duke Activity Status Index or 6
      minute walk test distance; (2) more severe valve stenosis as measured by
      projected aortic valve area at a normal transvalvular flow rate; and (3) reduced
      peak stress left ventricular ejection fraction, a composite measure accounting
      for both resting left ventricular function and contractile reserve.

PMID- 18824761
TI  - Pilot proteomic profile of differentially regulated proteins in right atrial
      appendage before and after cardiac surgery using cardioplegia and cardiopulmonary
      bypass.
AB  - BACKGROUND: Although highly protective, cardiac surgery using cardioplegia and
      cardiopulmonary bypass (CP/CPB) subjects myocardium to hypothermic reversible
      ischemic injury that can impair cardiac function which results in a greatly
      enhanced risk of mortality. Acute changes in myocardial contractile activity are
      likely regulated via protein modifications. We performed the following study to
      determine changes in the protein profile of human myocardium following CP/CPB.
      METHODS AND RESULTS: Right atrial appendage was collected from 8 male patients
      pre and post-CP/CPB. Atrial tissue lysates were subjected to 2-dimensional
      electrophoresis, total protein staining, gel averaging, and quantitative
      densitometry. Ten prominent spots regulated in response to CP/CPB were identified
      using mass spectrometry. Two hundred twenty-five and 256 protein spots were
      reliably detected in 2D-gels from pre- and post-CP/CPB patients, respectively.
      Five unique (ie, not detected post-CP/CPB) and 17 significantly increased spots
      were detected pre-CP/CPB. Thirty-four unique and 25 significantly increased spots
      were detected in the post-CP/CPB group. Identified proteins that changed after
      CP/CPB included: MLC-2a, ATP-synthase delta chain and Enoyl-CoenzymeA hydratase,
      glutathione-s-transferase omega, alpha-1-acid-glycoprotein, and
      phosphatidylethanolamine-binding protein. CONCLUSIONS: Cardiac surgery results in
      multiple consistent changes in the human myocardial protein profile. CP/CPB
      modifies specific cytoskeletal, metabolic, and inflammatory proteins potentially
      involved in deleterious effects of CP/CPB.

PMID- 18824762
TI  - The effects of mitral regurgitation alone are sufficient for leaflet remodeling.
AB  - BACKGROUND: Although chronic mitral regurgitation results in adverse left
      ventricular remodeling, its effect on the mitral valve leaflets per se is
      unknown. In a chronic ovine model, we tested whether isolated mitral
      regurgitation alone was sufficient to remodel the anterior mitral leaflet.
      METHODS AND RESULTS: Twenty-nine sheep were randomized to either control (CTRL,
      n=11) or experimental (HOLE, n=18) groups. In HOLE, a 2.8- to 4.8-mm diameter
      hole was punched in the middle scallop of the posterior mitral leaflet to create
      "pure" mitral regurgitation. At 12 weeks, the anterior mitral leaflet was
      analyzed immunohistochemically to assess markers of collagen and elastin
      synthesis as well as matrix metalloproteinases and proteoglycans. A
      semiquantitative grading scale for characteristics such as intensity and
      delineation of stain between layers was used to quantify differences between HOLE
      and CTRL specimens across the heterogeneous leaflet structure. At 12 weeks,
      mitral regurgitation grade was greater in HOLE versus CTRL (3.0+/-0.8 versus
      0.4+/-0.4, P<0.001). In HOLE anterior mitral leaflet, saffron-staining collagen
      (Movat) decreased, consistent with an increase in matrix metalloproteases
      throughout the leaflet. Type III collagen expression was increased in the
      midleaflet and free edge and expression of prolyl-4-hydroxylase (indicating
      collagen synthesis) was increased in the spongiosa layer. The proteoglycan
      decorin, also involved in collagen fibrillogenesis, was increased compared with
      CTRL (all P</=0.05). CONCLUSIONS: In HOLE anterior mitral leaflet, the increased
      expression of proteins related to collagen synthesis and matrix degradation
      suggests active matrix turnover. These are the first observations showing that
      regurgitation alone can stimulate mitral leaflet remodeling. Such leaflet
      remodeling needs to be considered in reparative surgical techniques.

PMID- 18824763
TI  - Saddle-shaped mitral valve annuloplasty rings experience lower forces compared
      with flat rings.
AB  - BACKGROUND: New insight into the 3D dynamic behavior of the mitral valve has
      prompted a reevaluation of annuloplasty ring designs. Force balance analysis
      indicates correlation between annulus forces and stresses in leaflets and chords.
      Improving this stress distribution can intuitively enhance the durability of
      mitral valve repair. We tested the hypothesis that saddle-shaped annuloplasty
      rings have superior uniform systolic force distribution compared with a
      nonuniform force distribution in flat annuloplasty rings. METHODS AND RESULTS:
      Sixteen 80-kg pigs had a flat (n=8) or saddle-shaped (n=8) mitral annuloplasty
      ring implanted. Mitral annulus 3D dynamic geometry was obtained with
      sonomicrometry before ring insertion. Strain gauges mounted on dedicated D-shaped
      rigid flat and saddle-shaped annuloplasty rings provided the intraoperative force
      distribution perpendicular to the annular plane. Average systolic annular height
      to commissural width ratio before ring implantation was 14.0%+/-1.6%. After flat
      and saddle shaped ring implantation, the annulus was fixed in the diastolic
      (9.0%+/-1.0%) and systolic (14.3%+/-1.3%) configuration, respectively (P<0.01).
      Force accumulation was seen from the anterior (0.72N+/-0.14N) and commissural
      annular segments (average 1.38N+/-0.27N) of the flat rings. In these segments,
      the difference between the 2 types of rings was statistically significant
      (P<0.05). The saddle-shaped annuloplasty rings did not experience forces
      statistically significantly larger than zero in any annular segments.
      CONCLUSIONS: Saddle-shaped annuloplasty rings provide superior uniform annular
      force distribution compared to flat rings and appear to represent a configuration
      that minimizes out-of-plane forces that could potentially be transmitted to
      leaflets and chords. This may have important implications for annuloplasty ring
      selections.

PMID- 18824764
TI  - Alterations in transmural myocardial strain: an early marker of left ventricular
      dysfunction in mitral regurgitation?
AB  - BACKGROUND: In asymptomatic patients with severe isolated mitral regurgitation
      (MR), identifying the onset of early left ventricular (LV) dysfunction can guide
      the timing of surgical intervention. We hypothesized that changes in LV
      transmural myocardial strain represent an early marker of LV dysfunction in an
      ovine chronic MR model. METHODS AND RESULTS: Sheep were randomized to control
      (CTRL, n=8) or experimental (EXP, n=12) groups. In EXP, a 3.5- or 4.8-mm hole was
      created in the posterior mitral leaflet to generate "pure" MR. Transmural
      beadsets were inserted into the lateral and anterior LV wall to radiographically
      measure 3-dimensional transmural strains during systole and diastolic filling, at
      1 and 12 weeks postoperatively. MR grade was higher in EXP than CTRL at 1 and 12
      weeks (3.0 [2-4] versus 0.5 [0-2]; 3.0 [1-4] versus 0.5 [0-1], respectively, both
      P<0.001). At 12 weeks, LV mass index was greater in EXP than CTRL (201+/-18
      versus 173+/-17 g/m(2); P<0.01). LVEDVI increased in EXP from 1 to 12 weeks
      (P=0.015). Between the 1 and 12 week values, the change in BNP (-4.5+/-4.4 versus
      -3.0+/-3.6 pmol/L), PRSW (9+/-13 versus 23+/-18 mm Hg), tau (-3+/-11 versus -4+/
      7 ms), and systolic strains was similar between EXP and CTRL. The changes in
      longitudinal diastolic filling strains between 1 and 12 weeks, however, were
      greater in EXP versus CTRL in the subendocardium (lateral: -0.08+/-0.05 versus
      0.02+/-0.14; anterior: -0.10+/-0.05 versus -0.02+/-0.07, both P<0.01).
      CONCLUSIONS: Twelve weeks of ovine "pure" MR caused LV remodeling with early
      changes in LV function detected by alterations in transmural myocardial strain,
      but not by changes in BNP, PRSW, or tau.

PMID- 18824765
TI  - A novel approach for reducing ischemic mitral regurgitation by injection of a
      polymer to reverse remodel and reposition displaced papillary muscles.
AB  - BACKGROUND: Ischemic mitral regurgitation (MR) relates to displacement of the
      papillary muscles from ischemic ventricular distortion. We tested the hypothesis
      that repositioning of the papillary muscles can be achieved by injection of
      polyvinyl-alcohol (PVA) polymer, a biologically inert biomaterial that has been
      specially formulated to produce an encapsulated, stable, resilient gel once
      injected into the myocardium. The purpose is to materially support the infarcted
      myocardium while at the same time repositioning the papillary muscles that become
      apically tethered in MR. METHODS AND RESULTS: Nine sheep underwent ligation of
      circumflex branches to produce acute ischemic MR. PVA polymer was then injected
      by echo guidance into the myocardium underlying the infarcted papillary muscle.
      Hemodynamic data, left ventricular ejection fraction, elastance, tau (relaxation
      constant), left ventricular stiffness coefficient, and 2-dimensional and 3
      dimensional echocardiograms were obtained post-MR and post-PVA injection. One
      animal died after coronary ligation and 2 did not develop MR. In the remaining 6,
      moderate MR developed. With PVA injection, the MR decreased significantly from
      moderate to trace-mild (vena contracta: 5+/-0.4 mm versus 2+/-0.7 mm, post-MR
      versus post-PVA injection; P<0.0001). This was associated with a decrease in
      infarcted papillary muscle-to-mitral annulus tethering distance (27+/-4 to 24+/-4
      mm, post-MR versus post-PVA, P<0.001). Importantly, PVA injection was not
      associated with significant decreases in left ventricular ejection fraction (43+/
      6% versus 37+/-4%, post-MR versus post-PVA, P=nonsignificant), elastance (3.5+/
      1.4 versus 2.9+/-1.3; post-MR versus post-PVA injection, P=nonsignificant).
      Measures of left ventricular diastolic function, tau (100+/-51 ms to 84+/-37 ms,
      post-MR versus post-PVA; P=nonsignificant), and left ventricular stiffness
      coefficient (0.18+/-0.12 versus 0.14+/-0.08, post-MR versus post-PVA;
      P=nonsignificant) did not increase post-PVA. CONCLUSIONS: PVA polymer injection
      resulted in acute reverse remodeling of the ventricle with papillary muscle
      repositioning to decrease MR. This was not associated with an adverse effect on
      left ventricular systolic and diastolic function. This new approach to alter
      pathological anatomy after infarction may offer an alternative strategy for
      relieving ischemic MR by correcting the position of the affected papillary
      muscle, thus relieving apical tethering.

PMID- 18824766
TI  - Loss of myocardial ischemic postconditioning in adenosine A1 and bradykinin B2
      receptors gene knockout mice.
AB  - BACKGROUND: Ischemic postconditioning (PostC) is a recently described
      cardioprotective modality against reperfusion injury, through series of brief
      reflow interruptions applied at the very onset of reperfusion. It is proposed
      that PostC can activate a complex cellular signaling cascade, in which cell
      membrane receptors could serve as the upstream triggers of PostC. However, the
      exact subtypes of such receptors remain controversial or uninvestigated. To this
      context, the purpose of present study was to determine the definitive role of
      adenosine A(1) and bradykinin B(1) and B(2) receptors in PostC. METHODS AND
      RESULTS: The hearts isolated from adult male C57BL/6J wild-type mice or the mice
      lacking adenosine A(1), or bradykinin B(1) or B(2) receptors subjected to zero
      flow global ischemia and reperfusion in a Langendorff model. PostC, consisting of
      6 cycles of 10 seconds of reperfusion and 10 seconds of ischemia, demonstrated
      significantly reduced myocardial infarct size (22.8+/-3.1%, mean+/-SEM) as
      compared with the non-PostC wild-type controls (35.1+/-2.8%, P<0.05). The infarct
      limiting protection of PostC was absent in adenosine A(1) receptor knockout mice
      (34.9+/-2.7%) or bradykinin B(2) receptor knockout mice (33.3+/-1.7%) and was
      partially attenuated in bradykinin B(1) receptor-deficient mice (25.6+/-2.9%;
      P>0.05). On the other hand, PostC did not significantly alter postischemic
      cardiac contractile function and coronary flow. CONCLUSIONS: With the use of
      three distinctive strains of gene knockout mice, the current study has provided
      the first conclusive evidence showing PostC-induced infarct-limiting
      cardioprotection could be triggered by activation of multiple types of cell
      membrane receptors, which include adenosine A(1) and bradykinin B(2) receptors.

PMID- 18824767
TI  - Mechanisms of sex differences in TNFR2-mediated cardioprotection.
AB  - BACKGROUND: TNFR1/TNFR2 signaling may mediate different cellular and molecular
      responses (injury versus protection) and the balance may be affected by sex
      hormones. Previous studies have shown that females have improved myocardial
      functional recovery, TNFR1 signaling resistance, and increased SOCS3 expression
      after acute ischemia/reperfusion when compared with males. However, it is unknown
      whether the TNFR2 pathway protects the myocardium from ischemia/reperfusion
      injury, and if so, whether sex differences exist in TNFR2-mediated
      cardioprotection. Therefore, we hypothesized that (1) TNFR2 mediates myocardial
      protection from ischemia/reperfusion through STAT3, SOCS3, and vascular
      endothelial growth factor in both sexes; and (2) TNFR2 elicits greater protective
      signaling in females compared with males. METHODS AND RESULTS: Isolated male and
      female mouse hearts from TNFR2 knockout, TNFR1/2 knockout, and wild-type
      (C57BL/6J or B6129SF2/J; n=5 to 6/group) were subjected to 20 minutes ischemia
      followed by 60 minutes reperfusion. TNFR2 deficiency decreased postischemic
      myocardial recovery in both sexes but had a greater effect on females. The
      deleterious effects of TNFR2 ablation were associated with a decrease in mRNA and
      protein levels of SOCS3, STAT3, and vascular endothelial growth factor as well as
      an increase in myocardial interleukin-1-beta production in female hearts.
      However, a significant increase in JNK activation and interleukin-1-beta protein
      levels was noted in male TNFR2KO hearts after ischemia/reperfusion. Additionally,
      TNFR1/2 knockout decreased myocardial function in female hearts but not males.
      This observation was associated with a decrease in mRNA levels of SOCS3, STAT3,
      and vascular endothelial growth factor and an increase in myocardial p38 mitogen
      activated protein kinase activation in females. CONCLUSIONS: Sex differences in
      the mechanisms of TNFR2-mediated cardioprotection occur by increasing STAT3,
      SOCS3, and vascular endothelial growth factor in females and by decreasing JNK in
      males.

PMID- 18824768
TI  - Calcium-activated potassium channels contribute to human coronary microvascular
      dysfunction after cardioplegic arrest.
AB  - BACKGROUND: Cardioplegic arrest (CP) followed by reperfusion after
      cardiopulmonary bypass induces coronary microvascular dysfunction. We
      investigated the role of calcium-activated potassium (K(Ca)) channels in this
      dysfunction in the human coronary microvasculature. METHODS AND RESULTS: Human
      atrial tissue was harvested before CP from a nonischemic segment and after CP
      from an atrial segment exposed to hyperkalemic cold blood CP (mean CP time, 58
      minutes) followed by 10-minute reperfusion. In vitro relaxation responses of
      precontracted arterioles (80 to 180 mum in diameter) in a pressurized no-flow
      state were examined in the presence of K(Ca) channel activators/blockers and
      several other vasodilators. We also examined expression and localization of K(Ca)
      channel gene products in the coronary microvasculature using reverse
      transcriptase-polymerase chain reaction, immunoblot, and immunofluorescence
      photomicroscopy. Post-CP reperfusion relaxation responses to the activator of
      intermediate and small conductance K(Ca) channels (IK(Ca)/SK(Ca)), NS309 (10(-5)
      M), and to the endothelium-dependent vasodilators, substance P (10(-8) M) and
      adenosine 5diphosphate (10(-5) M), were significantly reduced compared with pre
      CP responses (P<0.05, n=8/group). In contrast, relaxation responses to the
      activator of large conductance K(Ca) channels (BK(Ca)), NS1619 (10(-5) M), and to
      the endothelium-independent vasodilator, sodium nitroprusside (10(-4) M), were
      unchanged pre- and post-CP reperfusion (n=8/group). Endothelial denudation
      significantly diminished NS309-induced vasodilatation and abolished substance P-
      or adenosine 5 diphosphate-induced relaxation (P<0.05), but had no effect on
      relaxation induced by either NS1619 or sodium nitroprusside. The total
      polypeptide levels of BK(Ca), IK(Ca), and SK(Ca) and the expression of IK(Ca)
      mRNA were not altered post-CP reperfusion. CONCLUSIONS: Cardioplegic arrest
      followed by reperfusion after cardiopulmonary bypass causes microvascular
      dysfunction associated with and likely in part due to impaired function of SK(Ca)
      and IK(Ca) channels in the coronary microcirculation. These results suggest novel
      mechanisms of endothelial and smooth muscle microvascular dysfunction after
      cardiac surgery.

PMID- 18824769
TI  - Bioengineered three-layered robust and elastic artery using hemodynamically
      equivalent pulsatile bioreactor.
AB  - BACKGROUND: There is an essential demand for tissue engineered autologous small
      diameter vascular graft, which can function in arterial high pressure and flow
      circulation. We investigated the potential to engineer a three-layered robust and
      elastic artery using a novel hemodynamically-equivalent pulsatile bioreactor.
      METHODS AND RESULTS: Endothelial cells (ECs), smooth muscle cells (SMCs), and
      fibroblasts were harvested from bovine aorta. A polyglycolic acid (PGA) sheet and
      a polycaprolactone sheet seeded with SMCs, and a PGA sheet seeded with
      fibroblast, were wrapped in turn on a 6-mm diameter silicone tube and incubated
      in culture medium for 30 days. The supporting tube was removed, and the lumen was
      seeded with ECs and incubated for another 2 days. The pulsatile bioreactor
      culture, under regulated gradual increase in flow and pressure from 0.2 (0.5/0)
      L/min and 20 (40/15) mm Hg to 0.6 (1.4/0.2) L/min and 100 (120/80) mm Hg, was
      performed for an additional 2 weeks (n=10). The engineered vessels acquired
      distinctly similar appearance and elasticity as native arteries. Scanning
      electron microscopic examination and Von Willebrand factor staining demonstrated
      the presence of ECs spread over the lumen. Elastica Van Gieson and Masson
      Tricrome Stain revealed ample production of elastin and collagen in the
      engineered grafts. Alpha-SMA and calponin staining showed the presence of SMCs.
      Tensile tests demonstrated that engineered vessels acquired equivalent ultimate
      strength and similar elastic characteristics as native arteries (Ultimate
      Strength of Native: 882+/-133 kPa, Engineered: 827+/-155 kPa, each n=8).
      CONCLUSIONS: A robust and elastic small-diameter artery was engineered from three
      types of vascular cells using the physiological pulsatile bioreactor.

PMID- 18824770
TI  - Progesterone induces human leukocyte antigen-g expression in vascular endothelial
      and smooth muscle cells.
AB  - BACKGROUND: Human leukocyte antigen-G (HLA-G) expression in heart transplant
      patients has been negatively associated with acute cellular rejection and cardiac
      allograft vasculopathy. We assessed HLA-G expression in vascular human
      endothelial and smooth muscle cell cultures to determine if future therapeutic
      agents can be targeted toward inducing HLA-G expression to protect against
      allograft rejection and vasculopathy. METHODS AND RESULTS: Human coronary artery
      endothelial, aortic endothelial, and coronary artery smooth muscle cell cultures
      were exposed to cytokines (interferon-gamma or interleukin-10),
      hypoxia/reoxygenation stress, immunosuppressive agents (cyclosporine, sirolimus,
      or tacrolimus), or progesterone. HLA-G was not expressed by untreated, normoxic
      cells. Furthermore, maximal doses of interferon-gamma, interleukin-10,
      cyclosporine, sirolimus, or tacrolimus, as well as exposure to
      hypoxia/reoxygenation, failed to induce HLA-G expression. HLA-G, which has
      previously not been detected in adult vascular endothelial and smooth muscle
      cells, was detected by enzyme-linked immunosorbent assay and flow cytometry in
      human coronary artery endothelial, human coronary aortic endothelial, and human
      coronary artery smooth muscle cultures after incubation with progesterone in a
      dose-dependent manner (P<0.001) with no change in cellular proliferation ability
      or viability. This effect was partially blocked in the presence of mifepristone,
      a progesterone receptor antagonist (human coronary artery endothelial: 48.8+/
      15.6%; human coronary aortic endothelial: 59.5+/-9.5%; human coronary artery
      smooth muscle: 59.8+/-9.8% of control; P<0.05). Progesterone-induced HLA-G
      expression was not protective against hypoxia/reoxygenation injury. CONCLUSIONS:
      HLA-G is not expressed at baseline in vascular endothelial and smooth muscle
      cells but can be induced by exposure to progesterone. Although tightly regulated,
      induction of HLA-G expression in these cells may represent a promising and novel
      therapeutic strategy to protect against rejection and cardiac allograft
      vasculopathy after heart transplantation.

PMID- 18824771
TI  - Local delivery of imatinib mesylate (STI571)-incorporated nanoparticle ex vivo
      suppresses vein graft neointima formation.
AB  - BACKGROUND: Clinical outcome of surgical revascularization using autologous vein
      graft is limited by vein graft failure attributable to neointima formation.
      Platelet-derived growth factor (PDGF) plays a central role in the pathogenesis of
      vein graft failure. Therefore, we hypothesized that nanoparticle (NP)-mediated
      drug delivery system of PDGF-receptor (PDGF-R) tyrosine kinase inhibitor
      (imatinib mesylate: STI571) could be an innovative therapeutic strategy. METHODS
      AND RESULTS: Uptake of STI571-NP normalized PDGF-induced cell proliferation and
      migration. Excised rabbit jugular vein was treated ex vivo with PBS, STI571 only,
      FITC-NP, or STI571-NP, then interposed back into the carotid artery position. NP
      was detected in many cells in the neointima and media at 7 and 28 days after
      grafting. Significant neointima was formed 28 days after grafting in the PBS
      group; this neointima formation was suppressed in the STI571-NP group. STI571-NP
      treatment inhibited cell proliferation and phosphorylation of the PDGF-R-beta but
      did not affect inflammation and endothelial regeneration. CONCLUSIONS: STI571-NP
      induced suppression of vein graft neointima formation holds promise as a strategy
      for preventing vein graft failure.

PMID- 18824772
TI  - Survival after resection of primary cardiac tumors: a 48-year experience.
AB  - BACKGROUND: Primary cardiac tumors are rare but have the potential to cause
      significant morbidity if not treated in an appropriate and timely manner. To
      date, however, there have been no studies examining survival characteristics of
      patients who undergo surgical resection. METHODS AND RESULTS: From 1957 to 2006,
      323 consecutive patients underwent surgical resection of primary cardiac tumors;
      163 (50%) with myxomas, 83 (26%) with papillary fibroelastomas, 18 (6%) with
      fibromas, 12 (4%) with lipomas, 28 (9%) with other benign primary cardiac tumors,
      and 19 (6%) with primary malignant tumors. Operative (30 day) mortality was 2%
      (n=6). Univariate analysis indicated that patients who underwent resection of
      fibromas and myxomas had superior survival characteristics in comparison to the
      remainder of tumor variants; these results were consistent after adjusting for
      age at surgery, year of surgery, and cardiovascular risk factors. Based on
      actuarial characteristics of the 2002 U.S. population, patients who underwent
      myxoma resection had survival characteristics that were not significantly
      different from that of an age and gender matched population (SMR 1.11, P=0.57)
      whereas those who underwent resection of fibromas (SMR 11.17, P=0.002), papillary
      fibroelastomas (SMR 3.17, P=0.0003), lipomas (SMR 5.0, P=0.0003), other benign
      tumors (SMR 4.63, P=0.003), and malignant tumors (SMR 101, P<0.0001) had
      significantly poorer survival characteristics. Furthermore, malignant tumors in
      younger patients were highly fatal (HR 0.899, P<0.0001). Although the most
      significant predictor of mortality was tumor histology, survival was also
      influenced the by the duration of CPB and NYHA III/IV; the impact of these risk
      factors varied with time. The cumulative incidence of myxoma recurrence was 13%
      and occurred in a younger population (42 versus 57 years, P=0.003) with the risk
      of recurrence decreased after 4 years. CONCLUSIONS: Surgical resection of primary
      cardiac tumors is associated with excellent long-term survival; patients with
      cardiac myxomas have survival characteristics that are not significantly
      different from that of a general population. Predictors of mortality are
      primarily related to tumor histology but also include clinical characteristics
      such as symptomatology and duration of CPB.

PMID- 18824773
TI  - CCR2-mediated antiinflammatory effects of endothelial tetrahydrobiopterin inhibit
      vascular injury-induced accelerated atherosclerosis.
AB  - BACKGROUND: Vascular injury results in loss of endothelial nitric oxide (NO),
      production of reactive oxygen species (ROS), and the initiation of an
      inflammatory response. Both NO and ROS modulate inflammation through redox
      sensitive pathways. Tetrahydrobiopterin (BH4) is an essential cofactor for
      endothelial nitric oxide synthase (eNOS) that regulates enzymatic synthesis of
      either nitric oxide or ROS. We hypothesized that endothelial BH4 is an important
      regulator of inflammation and vascular remodeling. METHODS AND RESULTS:
      Endothelium-targeted overexpression of GTP cyclohydrolase 1 (GCH), the rate
      limiting enzyme in BH4 synthesis, increased levels of tetrahydrobiopterin (BH4),
      reduced endothelial superoxide, improved eNOS coupling, and reduced vein graft
      atherosclerosis in transgenic GCH/ApoE-KO mice compared to ApoE-KO controls.
      Immunohistochemistry using anti-MAC-3 and MAC-1 antibody staining revealed a
      marked reduction in vein graft macrophage content, as did RT-PCR expression of
      macrophage marker CD68 mRNA levels in GCH/ApoE-KO mice. When we investigated the
      potential mediators of this reduction, we discovered that mRNA and protein levels
      of MCP-1 (CCL2) but not RANTES (CCL5) were significantly reduced in GCH/ApoE-KO
      aortic tissue. Consistent with this finding we found a decrease in CCR2-mediated,
      but not CCR5-mediated, chemotaxis in vascular tissue and plasma samples from
      GCH/ApoE-KO animals. CONCLUSIONS: Increased endothelial BH4 reduces vein graft
      neointimal hyperplasia and atherosclerosis through a reduction in vascular
      inflammation. These findings highlight the importance of MCP-1/CCR2 signaling in
      the response to vascular injury and identify novel pathways linking endothelial
      BH4 to inflammation and vascular remodeling.

PMID- 18824774
TI  - Epicardial ultrasonic ablation of atrial fibrillation during concomitant cardiac
      surgery is a valid option in patients with ischemic heart disease.
AB  - BACKGROUND: Surgical therapy of atrial fibrillation concomitant to coronary
      bypass grafting using epicardial Ultrasound technology was assessed after a
      minimum 6-month follow-up. METHODS AND RESULTS: A cohort of 98 consecutive
      patients with a mean age of 72+/-7.58 years and a primary diagnosis of ischemic
      heart disease had surgery for structural disease. Coronary artery bypass grafting
      was isolated (n=51) or associated (n=47) with various combinations of aortic,
      mitral, tricuspid, and left ventricular restoration surgery. Atrial fibrillation
      duration ranged from 6 to 360 months (mean 71 months) and was permanent in 47
      patients, paroxysmal in 34, and persistent in 17. Left atrial mean diameter was
      48+/-6.71 mm. A circumferential ablation was performed off-pump, before the
      concomitant procedure, and was always associated with an epicardial mitral line
      lesion using the same technology. At 3-, 6-, and 12-month visits, patients were
      routinely evaluated by physical examination, ECG, chest X-ray, and 24-hour
      Holter. There were 1 early death (1%) and 4 extracardiac late deaths. A pacemaker
      was implanted in 4 patients. Mean follow-up time was 325 days, 2 patients being
      lost to follow-up. Freedom from atrial fibrillation and flutter at the 6-month
      visit was 84% for the entire population, 76% in patients with permanent, and 91%
      in patients with paroxysmal atrial fibrillation. At the 1-year visit, 85% were
      free from atrial fibrillation or flutter. CONCLUSIONS: Epicardial beating heart
      ablation using therapeutic ultrasound is safe, reliable, and can easily treat
      atrial fibrillation in a difficult surgical population of patients with primary
      ischemic heart disease.

PMID- 18824775
TI  - Impact of donor-to-recipient weight ratio on survival after heart
      transplantation: analysis of the United Network for Organ Sharing Database.
AB  - BACKGROUND: Generally accepted donor criteria for heart transplantation limit
      allografts from donors within approximately 20% to 30% of the recipient's weight.
      We analyzed the impact of donor-to-recipient weight ratio on survival after heart
      transplantation. METHODS AND RESULTS: Adult heart transplant recipients reported
      to the United Network for Organ Sharing from 1999 to 2007 were divided into 3
      groups based on donor-to-recipient weight ratio: <0.8, 0.8 to 1.2, and >1.2.
      Kaplan-Meier methodology was used to estimate survival. Propensity-adjusted Cox
      regression modeling was used to analyze predictors of mortality. A total of 15
      284 heart transplant recipients were analyzed; 2078 had weight ratio of <0.8,
      9684 had 0.8 to 1.2, and 3522 had >1.2. Kaplan-Meier survival was not
      statistically different between groups at 5 years (P=0.26). Among patients with
      weight ratio <0.8, 5-year survival was lower for recipients with high pulmonary
      vascular resistance (>4 Woods units; P=0.02). Among recipients with high
      pulmonary vascular resistance, 5-year survival was similar for those with weight
      ratio 0.8 to 1.2 and >1.2 (P=0.44). Furthermore, male recipients with elevated
      pulmonary vascular resistance who received hearts from female donors had a
      significantly worse survival than males who received hearts from male donors
      (P=0.01). Propensity-adjusted multivariable analysis demonstrated that weight
      ratio <0.8 did not predict mortality (hazard ratio, 1.09; 95% CI, 0.94 to 1.27;
      P=0.21). Five-year survival after propensity matching was not statistically
      different between those with weight ratio <0.8 versus >/=0.8 (P=0.37).
      CONCLUSIONS: Weight ratio did not predict mortality after heart transplantation.
      However, recipients with elevated pulmonary vascular resistance who received
      undersized hearts had poor survival. Furthermore, in the setting of high
      pulmonary vascular resistance, male recipients who received hearts from female
      donors had worse survival than those who received hearts from male donors.
      Extending donor criteria to include undersized hearts in select recipients should
      be considered.

PMID- 18824776
TI  - Biventricular assist devices as a bridge to heart transplantation in small
      children.
AB  - BACKGROUND: Experience with the use of biventricular assist device (BiVAD)
      support to bridge small children to heart transplantation is limited. METHODS AND
      RESULTS: We used BIVAD support (Berlin EXCOR) in 9 pediatric heart transplant
      candidates from 4/05 to 7/07. The median patient age was 1.7 years (12 days to 17
      years). The median patient weight was 9.4 kg (3 to 38 kg). All children were
      supported with multiple intravenous inotropes+/-mechanical ventilation (6) or
      ECMO (3) before BiVAD implantation. All had significant right ventricular
      dysfunction. The median pulmonary vascular resistance index (Rpi) was 6.0
      WU/m(2). Eight patients were successfully bridged to heart transplantation after
      a median duration of BiVAD support of 35 days (1 to 77 days). One death occurred
      after 10 days of support from perioperative renal failure in a 3 kg infant. Five
      patients required at least 1 blood pump change. One patient had a driveline
      infection requiring treatment. There were no acute neurological complications, no
      thromboembolic events, and no bleeding complications. In 2 patients with Rpi >10
      WU/m(2) unresponsive to pulmonary vasodilator therapy, Rpi dropped to 1.4 and 4.6
      WU/m(2), after 33 and 41 days of support, respectively. All 8 survivors underwent
      successful heart transplantation. Of 5 patients supported >30 days, 3 developed
      an extremely elevated (>90%) panel reactive antibody by ELISA that was not
      confirmed by other methods; none had a positive donor-specific retrospective
      crossmatch. There was 1 episode of rejection (with hemodynamic compromise) in the
      8 transplanted patients. Rpi was normal (<3 WU/m(2)) without pulmonary
      vasodilators in all patients within 3 months after transplant. There have been no
      deaths after transplant with a median follow-up of 19 months. CONCLUSIONS: BiVAD
      support can effectively be used in small children as a bridge to heart
      transplantation and can be accomplished with low mortality and morbidity. BiVAD
      support may offer an additional means to reverse extremely elevated pulmonary
      vascular resistance. Surveillance for HLA antibody sensitization during BiVAD
      support may be complicated by the development of non-HLA antibodies which may not
      reflect true HLA presensitization.

PMID- 18824777
TI  - Prediction of cardiac stability after weaning from left ventricular assist
      devices in patients with idiopathic dilated cardiomyopathy.
AB  - BACKGROUND: During ventricular assist device (VAD) unloading, cardiac recovery is
      possible even in patients with chronic heart failure (HF). We sought parameters
      predictive of cardiac stability after VAD removal. METHODS AND RESULTS: Among 81
      patients weaned since March 1995, a homogenous group of 35 with idiopathic
      dilated cardiomyopathy weaned from left VADs was selected. We evaluated echo data
      obtained before left VAD implantation and during "off-pump" trials before
      explantation, histological changes, and serum anti-beta1-adrenoceptor
      autoantibody disappearance during unloading, duration of unloading, and HF
      duration. Postweaning 10-year survival with native hearts reached 70.7+/-9.2%.
      During the first 5 years, HF recurred in 13 patients (37.1%). Only 6 (17.1%) died
      after HF recurrence or noncardiac complications related to left VAD explantation.
      Comparison of patients with and without long-term cardiac stability showed that
      stable patients were younger, HF history and recovery time during unloading
      shorter, and preweaning left ventricular assessment revealed higher left
      ventricular ejection fraction, lower short/long axis ratios, and higher end
      diastolic relative wall thicknesses. For left ventricular ejection fraction
      >/=45% at end diastolic diameter of </=55 mm, predictive value for >/=5-year
      cardiac stability was 87.5%. Left ventricular ejection fraction time course
      during the first 6 postweaning months appeared predictive for long-term
      stability. HF history >5 years and preweaning instability of cardiac improvement
      appeared predictive for HF recurrence. CONCLUSIONS: In idiopathic dilated
      cardiomyopathy, left VAD removal can be successful for >12 years even with
      incomplete cardiac recovery. Pre-explantation left ventricular ejection fraction,
      left ventricular end diastolic diameter and relative wall thicknesses, stability
      of unloading-induced cardiac recovery, duration of left VAD support, and HF
      duration before left VAD insertion allow identification of patients able to
      remain stable for >5 years. Time course of left ventricular ejection fraction
      during the first 6 postweaning months allows prognostic assessment.

PMID- 18824778
TI  - Implant wear mechanisms--basic approach.
AB  - Numerous parameters control the long-term performance of a total hip joint
      arthroplasty. The articulating motions between the femoral and the acetabular
      components produce wear debris in a hip implant. Surface roughness, clearance,
      coefficient of friction and sliding distance are found to be contributing
      parameters that affect wear rates. Wear produced in a hip implant leads to the
      loosening of a hip prosthesis and thus failure of the hip implant. Ultra-high
      molecular-weight polyethylene (UHMWPE) has been successfully used as an
      acetabular weight bearing component in the THR applications. Cross-linked UHMWPE
      was found to improve the lifespan of an artificial hip. A gradient cross-linking
      of UHMWPE has been observed to be a recent development in implant bearing
      materials. During in vitro studies, gradient cross-linked UHMWPE showed nearly
      undetectable wear rates.

PMID- 18824779
TI  - Cross-linking methods of electrospun fibrinogen scaffolds for tissue engineering
      applications.
AB  - The purpose of this study was to enhance the mechanical properties and slow the
      degradation of an electrospun fibrinogen scaffold, while maintaining the
      scaffold's high level of bioactivity. Three different cross-linkers were used to
      achieve this goal: glutaraldehyde vapour, 1-ethyl-3-(3-dimethylaminopropyl)
      carbodiimide hydrochloride (EDC) in ethanol and genipin in ethanol. Scaffolds
      with a fibrinogen concentration of 120 mg ml(-1) were electrospun and cross
      linked with one of the aforementioned cross-linkers. Mechanical properties were
      determined through uniaxial tensile testing performed on scaffolds incubated
      under standard culture conditions for 1 day, 7 days and 14 days. Cross-linked
      scaffolds were seeded with human foreskin fibroblasts (BJ-GFP-hTERT) and cultured
      for 7, 14 and 21 days, with histology and scanning electron microscopy performed
      upon completion of the time course. Mechanical testing revealed significantly
      increased peak stress and modulus values for the EDC and genipin cross-linked
      scaffolds, with significantly slowed degradation. However, cross-linking with EDC
      and genipin was shown to have some negative effect on the bioactivity of the
      scaffolds as cell migration throughout the thickness of the scaffold was slowed.

PMID- 18824780
TI  - Effect of Zn and Mg in tricalcium phosphate and in culture medium on apoptosis
      and actin ring formation of mature osteoclasts.
AB  - This study investigated the resorptive activity of osteoclasts on tricalcium
      phosphate (TCP), zinc-containing tricalcium phosphate (ZnTCP) and magnesium
      containing tricalcium phosphate (MgTCP) ceramics in different Zn- or Mg
      containing culture media. On the TCP ceramic, an increase in Zn ions in the
      culture medium within the range between 0.3 and 6.8 ppm significantly induced an
      increase in osteoclast apoptosis and a decrease in actin ring formation. However,
      even a high level of Mg ions up to 100 ppm in the culture medium was unlikely to
      induce an increase in osteoclast apoptosis. Mg ions in the MgTCP ceramics have no
      effect on osteoclast apoptosis and actin ring formation. There was almost no
      significant difference in osteoclast apoptosis and actin ring formation between
      ZnTCP and MgTCP ceramics which have the same solubility and dissolution rates. It
      is indicated that only an increase in Zn level outside resorption lacuna has an
      inhibitory effect on osteoclast resorption and that an increase in Zn level
      inside resorption lacuna could not influence the osteoclast activity.

PMID- 18824781
TI  - Effects of porosity and crystallinity of glass ceramics on the in vivo bioactive
      response.
AB  - Two types of glass ceramics with different porosities and crystallinities were
      produced by sintering 45S5 Bioglass particulates. The in vivo bioactive response
      of the glass ceramics was evaluated by implanting them in rabbit muscle sites.
      After six weeks implantation, silicon-rich networks were observed on both types
      of ceramics, but the number of networks was much larger in the poorly
      crystallized dense ceramics than in the well crystallized porous ones. This
      indicated that the crystallization of glass ceramics retarded the formation of
      networks on surfaces. Apatite precipitation was found in pore areas of the porous
      ceramics, but not on the dense ones, suggesting that porosity was necessary for
      glass ceramics to induce apatite precipitation in a rabbit model.

PMID- 18824782
TI  - Mouse blood vessel imaging by in-line x-ray phase-contrast imaging.
AB  - It is virtually impossible to observe blood vessels by conventional x-ray imaging
      techniques without using contrast agents. In addition, such x-ray systems are
      typically incapable of detecting vessels with diameters less than 200 microm.
      Here we show that vessels as small as 30 microm could be detected using in-line
      phase-contrast x-ray imaging without the use of contrast agents. Image quality
      was greatly improved by replacing resident blood with physiological saline.
      Furthermore, an entire branch of the portal vein from the main axial portal vein
      to the eighth generation of branching could be captured in a single phase
      contrast image. Prior to our work, detection of 30 microm diameter blood vessels
      could only be achieved using x-ray interferometry, which requires sophisticated x
      ray optics. Our results thus demonstrate that in-line phase-contrast x-ray
      imaging, using physiological saline as a contrast agent, provides an alternative
      to the interferometric method that can be much more easily implemented and also
      offers the advantage of a larger field of view. A possible application of this
      methodology is in animal tumor models, where it can be used to observe tumor
      angiogenesis and the treatment effects of antineoplastic agents.

PMID- 18824783
TI  - Investigation of misalignment in analyzer crystal based-CT and its effect.
AB  - Analyzer crystal-based computed tomography (ACB-CT) is a novel x-ray phase
      contrast computed tomography technique. In this paper, in order to extract the
      refraction angle, we analyzed the effect of misalignment on tomography-sliced
      images of ACB-CT. Two different methods were considered: the first, proposed by
      Chapman and Dilmanian, was based on two sets of projective image data taken at
      both sides of the rocking curve and with a half circle sample rotation and the
      second, recently proposed by our team, was based on only one set of projective
      image data taken at one side of the rocking curve but with a full circle sample
      rotation. Theoretical analysis and experimental results will show that the second
      method improves the quality of reconstructed CT images, also simplifying the ACB
      CT data acquisition procedure.

PMID- 18824784
TI  - MRI-induced heating of deep brain stimulation leads.
AB  - The radiofrequency (RF) field used in magnetic resonance imaging is scattered by
      medical implants. The scattered field of a deep brain stimulation lead can be
      very intense near the electrodes stimulating the brain. The effect is more
      pronounced if the lead behaves as a resonant antenna. In this paper, we examine
      the resonant length effect. We also use the finite element method to compute the
      near field for (i) the lead immersed in inhomogeneous tissue (fat, muscle, and
      brain tissues) and (ii) the lead connected to an implantable pulse generator.
      Electric field, specific absorption rate and induced temperature rise
      distributions have been obtained in the brain tissue surrounding the electrodes.
      The worst-case scenario has been evaluated by neglecting the effect of blood
      perfusion. The computed values are in good agreement with in vitro measurements
      made in the laboratory.

PMID- 18824785
TI  - Shading correction algorithm for improvement of cone-beam CT images in
      radiotherapy.
AB  - Cone-beam CT (CBCT) images have recently become an established modality for
      treatment verification in radiotherapy. However, identification of soft-tissue
      structures and the calculation of dose distributions based on CBCT images is
      often obstructed by image artefacts and poor consistency of density calibration.
      A robust method for voxel-by-voxel enhancement of CBCT images using a priori
      knowledge from the planning CT scan has been developed and implemented. CBCT
      scans were enhanced using a low spatial frequency grey scale shading function
      generated with the aid of a planning CT scan from the same patient. This
      circumvents the need for exact correspondence between CBCT and CT and the process
      is robust to the appearance of unshared features such as gas pockets. Enhancement
      was validated using patient CBCT images. CT numbers in regions of fat and muscle
      tissue in the processed CBCT were both within 1% of the values in the planning
      CT, as opposed to 10-20% different for the original CBCT. Visual assessment of
      processed CBCT images showed improvement in soft-tissue visibility, although some
      cases of artefact introduction were observed.

PMID- 18824786
TI  - Three-dimensional modelling of the human carotid artery using the lattice
      Boltzmann method: I. model and velocity analysis.
AB  - Numerical modelling is a powerful tool in the investigation of human blood flow
      and arterial diseases such as atherosclerosis. It is known that near wall
      velocity and shear are important in the pathogenesis and progression of
      atherosclerosis. In this paper results for a simulation of blood flow in a three
      dimensional carotid artery geometry using the lattice Boltzmann method are
      presented. The velocity fields in the body of the fluid are analysed at six times
      of interest during a physiologically accurate velocity waveform. It is found that
      the three-dimensional model agrees well with previous literature results for
      carotid artery flow. Regions of low near wall velocity and circulatory flow are
      observed near the outer wall of the bifurcation and in the lower regions of the
      external carotid artery, which are regions that are typically prone to
      atherosclerosis.

PMID- 18824787
TI  - Three-dimensional modelling of the human carotid artery using the lattice
      Boltzmann method: II. shear analysis.
AB  - Near-wall shear is known to be important in the pathogenesis and progression of
      atherosclerosis. In this paper, the shear field in a three-dimensional model of
      the human carotid artery is presented. The simulations are performed using the
      lattice Boltzmann model and are presented at six times of interest during a
      physiologically accurate velocity waveform. The near-wall shear rate and von
      Mises effective shear are also examined. Regions of low near-wall shear rates are
      observed near the outer wall of the bifurcation and in the lower regions of the
      external carotid artery. These are regions where low near-wall velocity and
      circulatory flows have been observed and are regions that are typically prone to
      atherosclerosis.

PMID- 18824788
TI  - Simulating tumor growth in confined heterogeneous environments.
AB  - The holy grail of computational tumor modeling is to develop a simulation tool
      that can be utilized in the clinic to predict neoplastic progression and propose
      individualized optimal treatment strategies. In order to develop such a
      predictive model, one must account for many of the complex processes involved in
      tumor growth. One interaction that has not been incorporated into computational
      models of neoplastic progression is the impact that organ-imposed physical
      confinement and heterogeneity have on tumor growth. For this reason, we have
      taken a cellular automaton algorithm that was originally designed to simulate
      spherically symmetric tumor growth and generalized the algorithm to incorporate
      the effects of tissue shape and structure. We show that models that do not
      account for organ/tissue geometry and topology lead to false conclusions about
      tumor spread, shape and size. The impact that confinement has on tumor growth is
      more pronounced when a neoplasm is growing close to, versus far from, the
      confining boundary. Thus, any clinical simulation tool of cancer progression must
      not only consider the shape and structure of the organ in which a tumor is
      growing, but must also consider the location of the tumor within the organ if it
      is to accurately predict neoplastic growth dynamics.

PMID- 18824789
TI  - Sensitivity-dependent model of protein-protein interaction networks.
AB  - The scale free structure p(k)-k(-gamma) of protein-protein interaction networks
      can be reproduced by a static physical model in simulation. We inspect the model
      theoretically, and find the key reason for the model generating apparent scale
      free degree distributions. This explanation provides a generic mechanism of
      'scale free' networks. Moreover, we predict the dependence of gamma on
      experimental protein concentrations or other sensitivity factors in detecting
      interactions, and find experimental evidence to support the prediction.

PMID- 18824790
TI  - Structural properties of replication origins in yeast DNA sequences.
AB  - Sequence-dependent DNA flexibility is an important structural property
      originating from the DNA 3D structure. In this paper, we investigate the DNA
      flexibility of the budding yeast (S. Cerevisiae) replication origins on a genome
      wide scale using flexibility parameters from two different models, the
      trinucleotide and the tetranucleotide models. Based on analyzing average
      flexibility profiles of 270 replication origins, we find that yeast replication
      origins are significantly rigid compared with their surrounding genomic regions.
      To further understand the highly distinctive property of replication origins, we
      compare the flexibility patterns between yeast replication origins and promoters,
      and find that they both contain significantly rigid DNAs. Our results suggest
      that DNA flexibility is an important factor that helps proteins recognize and
      bind the target sites in order to initiate DNA replication. Inspired by the role
      of the rigid region in promoters, we speculate that the rigid replication origins
      may facilitate binding of proteins, including the origin recognition complex
      (ORC), Cdc6, Cdt1 and the MCM2-7 complex.

PMID- 18824791
TI  - Physical model for membrane protrusions during spreading.
AB  - During cell spreading onto a substrate, the kinetics of the contact area is an
      observable quantity. This paper is concerned with a physical approach to modeling
      this process in the case of ameboid motility where the membrane detaches itself
      from the underlying cytoskeleton at the leading edge. The physical model we
      propose is based on previous reports which highlight that membrane tension
      regulates cell spreading. Using a phenomenological feedback loop to mimic stress
      dependent biochemistry, we show that the actin polymerization rate can be coupled
      to the stress which builds up at the margin of the contact area between the cell
      and the substrate. In the limit of small variation of membrane tension, we show
      that the actin polymerization rate can be written in a closed form. Our analysis
      defines characteristic lengths which depend on elastic properties of the membrane
      cytoskeleton complex, such as the membrane-cytoskeleton interaction, and on
      molecular parameters, the rate of actin polymerization. We discuss our model in
      the case of axi-symmetric and non-axi-symmetric spreading and we compute the
      characteristic time scales as a function of fundamental elastic constants such as
      the strength of membrane-cytoskeleton adherence.

PMID- 18824792
TI  - Sustainability assessment of advanced wastewater treatment technologies.
AB  - As a consequence of the EU Water Framework Directive more focus is now on
      discharges of hazardous substances from wastewater treatment plants and sewers.
      Thus, many municipalities in Denmark may have to adopt to future advanced
      treatment technologies. This paper describes a holistic assessment, which
      includes technical, economical and environmental aspects. The technical and
      economical assessment is performed on 5 advanced treatment technologies: sand
      filtration, ozone treatment, UV exclusively for disinfection of pathogenic
      microorganisms, membrane bioreactor (MBR) and UV in combination with advanced
      oxidation. The technical assessment is based on 12 hazardous substances
      comprising heavy metals, organic pollutants, endocrine disruptors as well as
      pathogenic microorganisms. The environmental assessment is performed by life
      cycle assessment (LCA) comprising 9 of the specific hazardous substances and
      three advanced treatment methods; sand filtration, ozone treatment and MBR. The
      technical and economic assessment showed that UV solely for disinfection purposes
      or ozone treatment is the most advantageous advanced treatment methods if the
      demands are restricted to pathogenic microorganisms. In terms of sustainability,
      sand filtration is the most advantageous method based on the technical and
      environmental assessment due to the low energy consumption and high efficiency
      with regards to removal of heavy metals.

PMID- 18824793
TI  - Optimized plan of centralized and decentralized wastewater reuse systems for
      housing development in the urban area of Xi'an, China.
AB  - In an arid and water deficient urban area, such as Xi'an in the northwest region
      of China, gardening and forestation often use large amounts of tap water.
      Therefore, there is a need for treated wastewater reuse for such purpose to
      mitigate urban water shortage, especially in the newly developed housing area,
      where a high green coverage is often required for both commercial value and
      living condition improvement. Supply of the treated wastewater through a
      centralized system which has been planned and partially constructed is one
      measure to meet such need, but it may require an extension of the distribution
      system for a full coverage of the whole city area. A supplementary measure is to
      construct decentralized wastewater treatment and reuse (DESAR) systems in areas
      that are distant from the planned centralized system. In order to optimize the
      plan of wastewater reuse for housing development in the urban area, the authors
      analyzed the existing plan of centralized wastewater reuse and the envisaged plan
      of housing development in Xi'an urban area. A method was proposed for selection
      of a feasible way of reclaimed water reuse from two options, namely centralized
      and decentralized ones, by introducing a critical distance L0 which depends on
      the relationship between the cost for DESAR system installation and that for
      water delivery pipeline construction. If the distance from the project site to
      the nearest access point of the centralized system L is shorter than L0 then
      using reclaim water from the centralized system becomes more feasible, and
      otherwise DESAR system installation becomes more feasible. A distribution map was
      thus obtained to show an optimized plan of centralized and decentralized
      wastewater reuse systems for housing development in Xi'an city. An example was
      also given to show the advantage of a DESAR system installed.

PMID- 18824794
TI  - Effect of full and partial-bed configuration on carbon removal performance of
      biological aerated filters.
AB  - A comparative study to explore the characteristics of partially and fully packed
      biological aerated filters (BAFs) in the removal of carbon pollutant, reveals
      that the partial-bed reactor can perform comparably well with the full-bed
      reactor. The organic removal rate was 5.34 kg COD m(-3) d(-1) at Organic Loading
      Rates (OLR) 5.80+/-0.31 kg COD m(-3) d(-1) for the full-bed, and 5.22 kg COD m(
      3) d(-1) at OLR 5.79+/-0.29 kg COD m(-3) d(-1) for the partial-bed. In the
      partial-bed system, where the masses of biomass were only 41-51% of those of the
      full-bed, the maximum carbon removal limit was still between 5 to 6 kg COD m(-3)
      d(-1). At organic loadings above 5.0 kg COD m(-3) d(-1), the carbon removal
      capacity in both systems was limited by the mass and activity of microorganisms.
      The SRT in the full and partial-bed reactors was primarily controlled by the
      biomass loss in the effluent and during backwash operation. The SRT was reduced
      from 20.08 days at OLR 4.18+/-0.20 kg COD m(-3) d(-1) to 7.62 days at OLR 5.80+/
      0.31 kg COD m(-3) d(-1) in the full-bed, and from 7.17 days to 4.21 days in the
      partial-bed. After all, SRT values in the partial-bed were always lower than
      those in the full-bed.

PMID- 18824795
TI  - Life-cycle energy and CO2 analysis of stormwater treatment devices.
AB  - Environmental impacts associated with the construction, maintenance, and disposal
      of low-impact stormwater management devices are one aspect that should be
      considered during decision-making and life-cycle assessment (LCA) is a suitable
      method for quantifying such impacts. This paper reports a pilot study that
      employs LCA to compare life-cycle energy requirements and CO2 emissions of two
      stormwater devices in New Zealand. The two devices are a raingarden servicing an
      urban feeder road, and a sand filter that could have been installed in its stead.
      With an assumed life-time of 50 years, the life-cycle energy requirements of the
      built raingarden were almost 20% less than for the sand filter, while the CO2
      emissions were 30% less. Our analysis shows that given the difference between the
      infiltration rates used in the raingarden design (0.3 m/day) and measured during
      monitoring (3 m/day) there was potential to make significantly greater life-time
      savings using a smaller design for the raingarden that would have also met the
      treatment efficiency expectations. The analysis highlights the significant
      contribution of transportation-of both materials and staff-and ongoing
      maintenance to a treatment device's life-cycle energy and CO2 profiles.

PMID- 18824796
TI  - Evaluation of methods for isolation of DNA for polymerase chain reaction (PCR)
      based identification of pathogenic bacteria from pure cultures and water samples.
AB  - Polymerase chain reaction (PCR) provides a reliable detection of pathogenic
      bacteria in water samples. However, this method can be adversely influenced by
      the purity of the DNA template. This is a particularly important obstacle when
      the bacterial DNA is directly extracted from water samples. In this study we
      compared the suitability of 8 different methods for isolation of bacterial DNA
      from pure cultures and 10 different methods for isolation of DNA from water
      samples. The quality of extracted DNA was assessed by PCR amplification of target
      sequences derived from uid (E. coli and Shigella sp.), tuf (Enterococcus sp.) and
      hns (Salmonella sp.). Results indicated that there are differences among the
      methods tested and only a few of them gave satisfactory results. The method based
      on alkaline lysis of bacterial suspension, which was developed in our laboratory,
      seemed to be efficient enough for the detection of bacteria from pure cultures.
      Detection of bacteria directly from water samples was more difficult. The
      modified method developed by Slusarenko was found as the best of the tested
      methods.

PMID- 18824797
TI  - Biological treatment of thin-film transistor liquid crystal display (TFT-LCD)
      wastewater.
AB  - The amount of pollutants produced during manufacturing processes of TFT-LCD (thin
      film transistor liquid crystal display) substantially increases due to an
      increasing production of the opto-electronic industry in Taiwan. The total amount
      of wastewater from TFT-LCD manufacturing plants is expected to exceed 200,000 CMD
      in the near future. Typically, organic solvents used in TFT-LCD manufacturing
      processes account for more than 33% of the total TFT-LCD wastewater. The main
      components of these organic solvents are composed of the stripper (dimethyl
      sulphoxide (DMSO) and monoethanolamine (MEA)), developer (tetra-methyl ammonium
      hydroxide (TMAH)) and chelating agents. These compounds are recognized as non-or
      slow-biodegradable organic compounds and little information is available
      regarding their biological treatability. In this study, the performance of an A/O
      SBR (anoxic/oxic sequencing batch reactor) treating synthetic TFT-LCD wastewater
      was evaluated. The long-term experimental results indicated that the A/O SBR was
      able to achieve stable and satisfactory removal performance for DMSO, MEA and
      TMAH at influent concentrations of 430, 800, and 190 mg/L, respectively. The
      removal efficiencies for all three compounds examined were more than 99%. In
      addition, batch tests were conducted to study the degradation kinetics of DMSO,
      MEA, and TMAH under aerobic, anoxic, and anaerobic conditions, respectively. The
      organic substrate of batch tests conducted included 400 mg/L of DMSO, 250 mg/L of
      MEA, and 120 mg/L of TMAH. For DMSO, specific DMSO degradation rates under
      aerobic and anoxic conditions were both lower than 4 mg DMSO/g VSS-hr. Under
      anaerobic conditions, the specific DMSO degradation rate was estimated to be 14
      mg DMSO/g VSS-hr, which was much higher than those obtained under aerobic and
      anoxic conditions. The optimum specific MEA and TMAH degradation rates were
      obtained under aerobic conditions with values of 26.5 mg MEA/g VSS-hr and 17.3 mg
      TMAH/g VSS-hr, respectively. Compared to aerobic conditions, anaerobic
      biodegradation of MEA and TMAH was much less significant with values of 5.6 mg
      MEA/g VSS-hr and 0 mg TMAH/g VSS-hr, respectively. In summary, biological
      treatment of TFT-LCD wastewater containing DMSO, MEA, and TMAH is feasible, but
      appropriate conditions for optimum biodegradation of DMSO, MEA, and TMAH are
      crucial and require carefully operational consideration.

PMID- 18824798
TI  - Theoretical analysis on non-uniformity of water distribution and influence of
      construction parameters on settling efficiency.
AB  - During the reconstruction of horizontal flow tanks into inclined settling tanks
      in Chinese water plants, uniformity of water distribution has not been solved
      theoretically. Based on the concepts of hydraulics, a model of inclined tanks,
      including the ratio (L/B) of tank length (L) to width (B), diameter of inclined
      tubes (d) and height of the water distribution area (h1) and so on, was
      established to simulate and analyze the effects of these parameters on Non
      Uniformity of Water Distribution (NUWD). The influences of NUWD on settling
      efficiency were also analyzed based on Yao's formula. Simulated results show that
      the ratio (L/B) has the greatest impact on NUWD, and the settling efficiency
      decreases with it. Under the conditions of q=10 or 20 m/h and L/B>or=5 or 3, the
      total forces imposed on down-sliding flocs tend to be zero, which reduces the
      separating efficiency. Moreover, critical settling velocity (CSV) of the first
      inclined tube will decrease with the increase of h1, and the optimal range of h1
      will be 1.2-1.6 m. The difference of CSV between the first tube and the average
      value of the tank u0 (shown as Delta(uF0-u0)) will increase with d and surface
      load (q).

PMID- 18824799
TI  - Advanced oxidation processes: mechanistic aspects.
AB  - The reactive intermediate in Advanced Oxidation Processes (AOPs) is the *OH
      radical. It may be generated by various approaches such as the Fenton reaction
      (Fe2+/H2O2), photo-Fenton reaction (Fe3+/H2O2/hnu), UV/H2O2, peroxone reaction
      (O3/H2O2), O3/UV, O3/activated carbon, O3/dissolved organic carbon (DOC) of water
      matrix, ionizing radiation, vacuum UV, and ultrasound. The underlying reactions
      and *OH formation efficiencies are discussed. The key reactions of *OH radicals
      also addressed in this review.

PMID- 18824800
TI  - Characterization of bacterial biofilm communities in tertiary treatment processes
      for wastewater reclamation and reuse.
AB  - The concern with wastewater reuse as a sustainable water resource in urban areas
      has been growing. For the reclamation and distribution of wastewater, biofilm
      development deserves careful attention from the point of view of its promotion
      (e.g. biofiltration) and inhibition (e.g. clogging and hygiene problems). As the
      first step to control biofilm development, bacterial biofilm communities in
      tertiary treatment processes were characterized by using molecular biological
      methods. The result of clone library analysis showed that Nitrospirae-related
      (nitrite-oxydizing bacteria) and Acidobacteria-related (probably oligotrophic
      bacteria) groups were dominant. The ratio of the Nitrospirae-related group to the
      Acidobacteria-related group was associated with ammonia load, whereas other
      operational conditions (process, media, temperature, salt) did not clearly affect
      the phylum-level community or the dominant sequence of nitrifying bacteria. The
      result of real-time PCR also indicated that high ammonia load promotes the
      proliferation of nitrite- and ammonia-oxidizing bacteria. Regarding water supply
      systems, some researchers also have suggested the dominance of Nitrospirae- and
      Acidobacteria-related groups in biofilm formed on water distribution pipes. In
      tertiary wastewater treatment, therefore, it is concluded that oligotrophic and
      autotrophic bacteria are the dominant groups in biofilm samples because
      assimilable organic carbon is too poor to proliferate various heterotrophic
      bacteria.

PMID- 18824801
TI  - Advanced H2O2 oxidation for diethyl phthalate degradation in treated effluents:
      effect of nitrate on oxidation and a pilot-scale AOP operation.
AB  - One of the objectives of this study was to delineate the effect of nitrate on
      diethyl phthalate (DEP) oxidation by conducting a bench-scale ultraviolet
      (UV)/H2O2 and O3/H2O2 operations as suggested in a previous study. We also aim to
      investigate DEP oxidation at various UV doses and H2O2 concentrations by
      performing a pilot-scale advanced oxidation processes (AOP) system, into which a
      portion of the effluent from a pilot-scale membrane bioreactor (MBR) plant was
      pumped. In the bench-scale AOP operation, the O3 oxidation alone as well as the
      UV irradiation without H2O2 addition could be among the desirable alternatives
      for the efficient removal of DEP dissolved in aqueous solutions at a low DEP
      concentration range of 85+/-15 microg/L. The adverse effect in the UV/H2O2
      process was significantly greater than that in the UV oxidation alone, and its
      oxidation was almost halved by the nitrate. However, the nitrate clearly enhanced
      the DEP oxidation in the O3 oxidation and O3/H2O2 process. Especially, the
      addition of nitrate almost doubled the DEP oxidation efficiency in the O3/H2O2
      process. The series of pilot-scale AOP operations confirmed that about 30-50% of
      DEP dissolved in the treated MBR effluent streams was, at least, oxidized by the
      O3 oxidation alone as well as the UV irradiation without H2O2 addition. The UV
      photolysis of H2O2 was most effective for DEP degradation with an H2O2
      concentration of 40 mg/L at a UV dose of 500 mJ/cm2.

PMID- 18824802
TI  - Hydrological analysis of single and dual storage systems for stormwater
      harvesting.
AB  - As stormwater flows are intermittent, the requirement to store urban runoff is
      important to the design of a stormwater re-use scheme. In many urban areas, the
      space available to provide storage is limited and thus the need to optimise the
      storage volume becomes critical. This paper will highlight the advantages and
      disadvantages of two different approaches of providing storage: 1) a single
      shallow storage (0.5 m depth) in which stormwater capture and a balanced release
      to supply users is provided by the one unit; and 2) a dual system in which the
      functions of stormwater capture and supply release are provided by two separate
      deeper storage units (2 m depth). The comparison between the two strategies is
      supported by water balance modelling assessing the supply reliability and storage
      volume requirements for both options. Above a critical volumetric capacity, the
      supply yield of a dual storage system is higher than that from a single storage
      of equal volume mainly because of a smaller assumed footprint. The single storage
      exhibited greater evaporation loss and is more susceptible to algae blooms due to
      long water residence times. Results of the comparison provide guidance to the
      design of more efficient storages associated with stormwater harvesting systems.

PMID- 18824803
TI  - The role of reactive oxygen species in Staphylococcus aureus photoinactivation by
      methylene blue.
AB  - Methylene blue (MB) has been shown to photoinduce the direct inactivation of Gram
      positive bacteria Staphylococcus aureus (S. aureus) in water. We have
      investigated the mechanism of S. aureus photoinactivation conducting firstly
      sodium azide (reactive ion N3-), as a good physical singlet oxygen quencher, then
      the amino acids tryptophan (Trp), as a non-specific singlet oxygen quencher and
      the mannitol, as an hydroxyl free radical scavenger. Inactivation of MB
      photosensitization is the antioxidants type dependent. When the bacteria was
      treated with MB (20 microM) under light during 10 min of exposure, it was found
      that survival fraction had decreased dramatically to about 31.27+/-5.39%. The
      presence of sodium azide and Trp failed to shown any protection from the MB
      photodynamic activity. In the presence of mannitol, S. aureus could be protected,
      reaching a protection level of about 27%. It is possible that the photodynamic
      activity of MB occurred in part, via a Type I mechanism in which *OH was
      produced.The interactions between MB and S. aureus were studied
      spectrophotometrically. This demonstrated that a metachromatic reaction took
      place between MB and S. aureus bacteria. Furthermore, S. aureus bacteria induced
      additional dimerization of MB.

PMID- 18824804
TI  - Investigation of formaldehyde pollution of tap water and rain water using a novel
      visual colorimetry.
AB  - The pollution of tap water and rain water with formaldehyde in Toyama Pref.,
      Japan was investigated by means of a simple, rapid and cost-effective visual
      colorimetry developed by us. The levels of formaldehyde in three tap waters from
      different sources of dams on mountainside and a well-water pumped in urban area
      in Toyama Pref. were lower than 0.01 mg L(-1) that was the detection limit of the
      colorimetry. On the other hand, rain waters were seriously polluted with
      formaldehyde. Rain waters were sampled from three different sites (urban area,
      top of hill and industrial area) in Toyama Pref. from autumn to winter in 2006.
      The levels of formaldehyde in the rain waters ranged from 0.07 to 0.30 mg L(-1).
      The analytical results by the visual colorimetry were in good agreement with
      those obtained by GC-MS method. It was confirmed that the colorimetry is
      excellent for practical use for the determination of formaldehyde. It must be
      concerned about the pollution of rainwater with formaldehyde, when rain water is
      applied for tap water and miscellaneous purpose.

PMID- 18824805
TI  - Biosorption of Pb2+ and Cd2+ in a fixed bed column with immobilised Chorella sp.
      biomass.
AB  - The biosorption of Pb2+ and Cd2+ in a fixed bed column by immobilised Chlorella
      sp. was characterised in a fixed bed column. Effect of initial concentration of
      Pb2+ and Cd2+, pH, and pellet size on the biosorption capacity was studied, at
      laboratory scale, using a factorial experiment design 2(3), in a 10 cm heightx1
      cm of diameter continuous flow column packed with immobilised biomass.
      Equilibrium uptake of Pb2+ and Cd2+, increased with increasing initial metal ion
      concentration. It was favoured to pH 5, with a pellet of 5 mm of diameter.
      Langmuir model described the biosorption equilibrium of both metals.The
      biosorption of each single cation was studied too in a large column (50 cm
      heightx5 cm of diameter) at bench scale with a range of flow of 40 to 80 mL min(
      1). The mass transfer coefficient was determined fitting the experimental data to
      continuity equations that were discretised in the radial terms with orthogonal
      collocation method.

PMID- 18824806
TI  - Pretreatment of wastewater containing a mixture of organic pollutants obtained
      from a CC2 plant by coagulation.
AB  - Coagulation is one of the most important physicochemical treatment steps in
      industrial wastewater to reduce the suspended and colloidal materials responsible
      for colour and turbidity of the wastewater. The manufacturing plant of N,N'
      Dichloro bis (2,4,6-trichlorophenyl) urea (CC2) produces wastewater containing
      pyridine, acetic acid and diphenyl urea (DPU). The wastewater also contains lot
      of suspended solids like CC2 and various poly-aromatic compounds. In our present
      investigation, our basic aim was to find an effective coagulation process for the
      pretreatment of wastewater discharged from the CC2 plant. Studies were conducted
      to find out a suitable and effective coagulant for pretreatment of this
      wastewater. Various coagulating agents such as alum, ferric chloride, sodium
      carboxymethyl cellulose (Na-CMC) were used. Alum was found to be the most
      effective coagulant. Coagulation of the wastewater resulted in the total
      suspended solids (TSS) removal in the range of 92-94% and chemical oxygen demand
      (COD) removal in the range of 59 to 65% at a dose of 500 mg L(-1) of alum at a
      pH>or=7.0. After coagulation the concentration of pyridine in wastewater was
      found to be reduced by 10.0% and that of DPU 40-45% with a dosage of 500 mg L(-1)
      alum.

PMID- 18824807
TI  - Mechanism studies on chlorine and potassium permanganate degradation of
      microcystin-LR in water using high-performance liquid chromatography tandem mass
      spectrometry.
AB  - The presence of microystins (MCs) in water has the potential to harm people's
      health. In the MCs various isomers, MC-LR has the strongest toxicity and is the
      most harmful one. At present, several kinds of pre-oxidants, which are commonly
      used in water treatment process, are effective to remove MC-LR. However, it is
      still not clear about their degeneration mechanisms. Chlorine and potassium
      permanganate were selected in the present work since they are used worldwide for
      preoxidation treatment. Using the testing method of HPLC-MS, studies on the
      degeneration of MC-LR were conducted. The results indicate that HPLC-MS is
      creditable and sensitive. It was also found that linear relationship between
      concentration of MC-LR and peak area holds in the range of 5-500 microg.L(-1) on
      the calibration curves, the correlation coefficient (R2) is 0.9993. Under the
      general condition of oxidant dose and reaction time, MC-LR was degraded rapidly.
      With active chlorine and potassium permanganate the degradation reaction followed
      the mode of first-order kinetics. The molecular weight of the degradation product
      was determined through analyzing the full-scan mass spectrum of MC-LR. And the
      oxidative degradation mechanism of MC-LR was discussed as well.

PMID- 18824808
TI  - Evaluation of performance and microbial ecology of sequencing batch reactor and
      membrane bioreactor treating thin-film transistor liquid crystal display
      wastewater.
AB  - In Taiwan, a substantial amount of thin-film transistor liquid crystal display
      (TFT-LCD) wastewater is produced daily due to an increasing production of the
      opto-electronic industry in recent years. The main components of TFT-LCD
      wastewater include dimethyl sulphoxide (DMSO), monoethanolamine (MEA), and tetra
      methyl ammonium hydroxide (TMAH), which are recognized as non-or slow
      biodegradable organic compounds and limited information is available regarding
      their biological treatablility. This study was conducted to evaluate the long
      term performance of two bioreactors, anaerobic-aerobic (A/O) sequencing batch
      reactor (SBR) and aerobic membrane bioreactor (MBR), treating synthetic TFT-LCD
      wastewater containing DMSO, MEA, and TMAH with different loadings. For the A/O
      SBR, the influent wastewater was composed of 800 mg MEA/L, 430 mg DMSO/L, and 90
      mg TMAH/L, respectively. After reaching steady-state, SBR was able to achieve
      more than 99% degradation efficiencies for the three compounds examined. For the
      case of aerobic MBR, the influent wastewater was composed of 550 mg MEA/L, 270 mg
      DMSO/L, and 330 mg TMAH/L, respectively, and degradation efficiencies for the
      three compounds achieved more than 99%. Although both different reactors shared
      similar and satisfactory degradation efficiencies for DMSO, MEA, and TMAH, the
      microbial ecology of these two reactors, as elucidated with molecular methods,
      was apparently different. The 16S rDNA-based cloning/sequencing results indicated
      that the dominant sequences retrieved from the aerobic MBR, including
      Hyphomicrobium denitrificans, Hyphomicrobium zavarzinii, Rhodobacter sp., and
      Methyloversatilis universalis, showed a clear linkage to their physiological
      properties of DMSO and TMAH degradation. On the other hand, Zoogloea sp.,
      Chlorobium chlorochromatii, Agricultural soil bacterium, and Flavosolibacter
      ginsengiterrae were proliferated in the A/O SBR Run1, while Thiobacillus sp.,
      Nitrosomonas sp., Thauera aromatica and Azoarcus sp. became dominant in Run2.
      Furthermore, the sequences retrieved from different reactors were used to
      establish the terminal restriction fragment length polymorphism (TRFLP)
      fingerprint methodology for monitoring the dynamics of dominant degrading
      bacteria in the aerobic MBR treating TFT-LCD wastewater.

PMID- 18824809
TI  - Removal of arsenic from groundwater by arsenite-oxidizing bacteria.
AB  - The presence of arsenic in groundwater has been of great public concern because
      of its high toxicity. For purification of arsenic-contaminated groundwater,
      bacterial oxidation of arsenite, As(III), with a chemical adsorption process was
      examined in this study. After As(III) oxidation to arsenate, As(V), arsenic is
      easily removable from contaminated groundwater because As(V) is more adsorptive
      to absorbents than As(III). By acclimation to As(III) of high concentrations, a
      mixed culture of heterotrophic bacteria with high As(III)-oxidizing activity was
      obtained from a soil sample that was free from contamination. With initial
      concentration up to 1,500 mg l(-1) As(III), the mixed culture showed high As(III)
      oxidizing activity at pH values of 7-10 and at temperatures of 25-35 degrees C.
      The mixed culture contained several genera of heterotrophic As(III)-oxidizing and
      arsenic-tolerant bacteria: Haemophilus, Micrococcus, and Bacillus. Activated
      alumina was added to the basal salt medium containing 75 mg l(-1) As(III) before
      and after bacterial oxidation. Arsenic removal by activated alumina was greatly
      enhanced by bacterial oxidation of As(III) to As(V). The isotherms of As(III) and
      As(V) onto activated alumina verified that bacterial As(III) oxidation is a
      helpful pretreatment process for the conventional adsorption process for arsenic
      removal.

PMID- 18824810
TI  - Kinetics of growth and multi substrate degradation by an indigenous mixed
      microbial culture isolated from a wastewater treatment plant in Guwahati, India.
AB  - An indigenous mixed culture of microorganisms, isolated from a sewage treatment
      plant, was investigated for its potential to simultaneously degrade phenol and m
      cresol during its growth in batch shake flasks. 2(2) full factorial designs with
      the two substrates as the factors, at two different levels and two different
      initial concentration ranges, were employed to carry out the biodegradation
      experiments. For complete utilisation of phenol and m-cresol, the culture took a
      minimum duration of 21 hrs at their low concentration of 100 mg/L each, and a
      maximum duration of 187 hrs at high concentration of 600 mg/L each in the
      multisubstrate system. The biodegradation results also showed that the presence
      of phenol in low concentration range (100-300 mg/L did not inhibit m-cresol
      biodegradation; on the other hand, presence of m-cresol inhibited phenol
      biodegradation by the culture. Moreover, irrespective of the concentrations used,
      phenol was degraded preferentially and earlier than m-cresol. During the culture
      growth, a lag phase was observed above a combined concentration of 500 mg/L i.e.,
      200 mg/L m-cresol and 300 mg/L of phenol and above). Statistical analysis of the
      specific growth rate of the culture in the multisubstrate system was also
      performed in the form of ANOVA and Student 't' test, which gave good
      interpretation in terms of main and interaction effects of the substrates.

PMID- 18824811
TI  - Application of real-time polymerase chain reaction (PCR) coupled with ethidium
      monoazide treatment for selective quantification of viable bacteria in aquatic
      environment.
AB  - Ethidium monoazide (EMA) was used to quantify DNA selectively from viable cells
      with healthy membrane/cell wall system, but not from dead cells, of a target
      bacterium in the aquatic environment using real-time PCR. Spiking experiments to
      determine the EMA treatment conditions showed that EMA treatment with EMA at 10
      25 microg/ml and subsequent halogen light exposure for 2 min was suitable for
      selective quantification of DNA from viable cells in an aquatic sample using real
      time PCR coupled with EMA treatment (real-time EMA-PCR). Optimized real-time EMA
      PCR was applied in combination with culture-based method and conventional real
      time PCR without EMA treatment to elucidate the behavior of an Escherichia coli
      strain inoculated into a pond water microcosm. Quantification results obtained
      using real-time EMA-PCR were lower than those by conventional real-time PCR
      without EMA treatment and higher than those by culture-based method. The results
      suggest that quantification by real-time EMA-PCR seemed to represent the viable
      population, which would partly include viable but non-culturable state bacteria.
      Real-time EMA-PCR optimized here can be a useful tool for selective monitoring of
      the viable population of a target bacterium in the aquatic environment, and
      thereby contribute to assessment of potential microbial risks generated from
      waterborne pathogenic bacteria.

PMID- 18824812
TI  - Granular biomass capable of partial nitritation and anammox.
AB  - A novel and efficient way of removing nitrogen from wastewater poor in
      biodegradable organic carbon, is the combination of partial nitritation and
      anoxic ammonium oxidation (anammox), as in the one-stage oxygen-limited
      autotrophic nitrification/denitrification (OLAND) process. Since anoxic ammonium
      oxidizing bacteria grow very slowly, maximum biomass retention in the reactor is
      required. In this study, a lab-scale sequencing batch reactor (SBR) was used to
      develop granular, rapidly settling biomass. With SBR cycles of one hour and a
      minimum biomass settling velocity of 0.7 m/h, OLAND granules were formed in 1.5
      months and the nitrogen removal rate increased from 50 to 450 mg N L(-1) d(-1) in
      2 months. The granules had a mean diameter of 1.8 mm and their aerobic and anoxic
      ammonium-oxidizing activities were well equilibrated to perform the OLAND
      reaction. Fluorescent in-situ hybridization (FISH) demonstrated the presence of
      both beta-proteobacterial aerobic ammonium oxidizers and planctomycetes (among
      which anoxic ammonium oxidizers) in the granules. The presented results show the
      applicability of rapidly settling granular biomass for one-stage partial
      nitritation and anammox.

PMID- 18824813
TI  - Microbial community of anammox bacteria immobilized in polyethylene glycol gel
      carrier.
AB  - Anaerobic ammonium oxidation (anammox) is a recently discovered microbial pathway
      in the biological nitrogen cycle and a new cost-effective way to remove ammonium
      from wastewater. We have so far developed new immobilization technique that
      anammox bacteria entrapped in polyethylene glycol (PEG) gel carrier. However,
      fate and behavior of anammox bacteria in a gel carrier is not well understood. In
      the present study, we focused on the population changes of anammox bacteria in a
      gel carrier. Three specific primer sets were designed for real-time PCR. For
      quantification of anammox bacteria in a gel carrier, real-time PCR was performed.
      The anammox bacteria related to HPT-WU-N03 clone were increased the rate in
      anammox population, and found to be a major population of anammox bacteria in a
      gel carrier. Furthermore, from the results of nitrogen removal performance and
      quantification of anammox bacteria, the correlation coefficient between copy
      numbers of anammox bacteria and nitrogen conversion rate was calculated as 0.947
      in total anammox population. This is the first report that population changes of
      anammox bacteria immobilized in a gel carrier were evaluated.

PMID- 18824814
TI  - Removal of selected pharmaceuticals by chlorination, coagulation-sedimentation
      and powdered activated carbon treatment.
AB  - Removal property of nine pharmaceuticals (clofibric acid, diclofenac, fenoprofen,
      gemfibrozil, ibuprofen, indomethacin, ketoprofen, naproxen and propyphenazone) by
      chlorination, coagulation-sedimentation and powdered activated carbon treatment
      was examined by laboratory-scale experiments under the conditions close to actual
      drinking water treatment processes. Indomethacin and propyphenazone were
      completely degraded by chlorination within 30 minutes, but others remained around
      30% (naproxen and diclofenac) or more than 80% of the initial concentration after
      24 hours. A couple of unidentified peaks in a chromatogram of the chlorinated
      samples suggested the formation of unknown chlorination by-products. Competitive
      adsorption was observed when the mixed solution of the target pharmaceuticals was
      subjected to batch adsorption test with powdered activated carbon. Clofibric acid
      and ibuprofen, which were relatively less hydrophobic among the nine compounds,
      persisted around 60% of the initial concentration after 3 hours of contact time.
      Removal performance in actual drinking water treatment would become lower due to
      existence of other competitive substances in raw water (e.g. natural organic
      matter). Coagulation-sedimentation using polyaluminium chloride hardly removed
      most of the pharmaceuticals even under its optimal dose for turbidity removal. It
      is suggested that the most part of pharmaceuticals in raw water might persist in
      the course of conventional drinking water treatments.

PMID- 18824815
TI  - Natural attenuation of chloroethenes: identification of sequential
      reductive/oxidative biodegradation by microcosm studies.
AB  - A different lines of evidence approach for investigation of biodegradation
      processes at a chloroethene contaminated site showed well corresponding results
      of pollutant profiles, redox zonation, characterisation of autochthonic
      microflora and microcosm studies. In particular microcosm studies allowed
      identification of the predominating degradation pathways. Perchloroethene and
      trichloroethene are reductively chlorinated to mainly cis-1,2-dichloroethene
      (cDCE) under anaerobic conditions. Further reductive degradation to vinyl
      chloride (VC) is restricted to a distinct strongly anaerobic zone in the plume.
      Addition of high amounts of sediment material (80 vol%) to groundwater microcosms
      enabled reductive dechlorination without amendment with further auxiliary
      substrates. Reductive dechlorination was not irreversibly hindered by initially
      high nitrate concentrations and initially high oxidation-reduction potential. The
      products of anaerobic degradation cDCE and VC are subsequently aerobically
      mineralised, even when only low oxygen concentrations are available. Anaerobic
      oxidative degradation could not be proven in this study.

PMID- 18824816
TI  - Photodegradation of sulphadimethoxine in water by medium pressure UV lamp.
AB  - The photodegradation rate of sulphadimethoxine (SMT) in water was studied under
      polychromatic UV light, in a bench scale apparatus. SMT photolysis was carried
      out at pH levels of 2.5, 6.5 and 10 to study the impact of acid base properties
      on the degradation of SMT. The highest SMT photolysis fluence based rate was
      found at pH=2.5 (k=7.22x10(-4) cm2/mJ) and the lowest rate at pH=10 (k=4.72x10(
      4) cm2/mJ), thus the reaction rate decreases with an increase in pH between pH
      values of 2.5-10. Results indicated that direct photolysis is not satisfactory
      for degradation of SMT by polychromatic UV lamp as a fluence of approximately
      7,000 mJ/cm2 is needed to break down 99% of SMT at pH 6.5. The photodegradation
      products of SMT were studied at various pH values. Photodegradation of SMT
      results in dissimilar relative amounts of intermediates formed at different pH
      values which may exert a photon demand and impact on SMT photodegradation rate.

PMID- 18824817
TI  - Maternal obesity and pregnancy.
AB  - Obesity is a global health problem that is increasing in prevalence. The World
      Health Organization characterizes obesity as a pandemic issue, with a higher
      prevalence in females than males. Thus, many pregnant patients are seen with high
      body mass index (BMI). Obesity during pregnancy is considered a high-risk state
      because it is associated with many complications. Compared with normal-weight
      patients, obese patients have a higher prevalence of infertility. Once they
      conceive, they have higher rate of early miscarriage and congenital anomalies,
      including neural tube defects. Besides the coexistence of preexisting diabetes
      mellitus and chronic hypertension, obese women are more likely to have pregnancy
      induced hypertension, gestational diabetes, thromboembolism, macrosomia, and
      spontaneous intrauterine demises in the latter half of pregnancy. Obese women
      also require instrument or Cesarean section delivery more often than average
      weight women. Following Cesarean section delivery, obese women have a higher
      incidence of wound infection and disruption. Irrespective of the delivery mode,
      children born to obese mothers have a higher incidence of macrosomia and
      associated shoulder dystocia, which can be highly unpredictable. In addition to
      being large at birth, children born to obese mothers are also more susceptible to
      obesity in adolescence and adulthood. Prevention is the best way to prevent this
      problem. As pregnancy is the worst time to lose weight, women with a high BMI
      should be encouraged to lose weight prior to conceiving. During preconception
      counseling, they should be educated about the complications associated with high
      a BMI. Obese women should also be screened for hypertension and diabetes
      mellitus. In early pregnancy, besides being watchful about the higher association
      of miscarriage, obese women should be screened with ultrasound for congenital
      anomalies around 18 to 22 weeks. The ultrasound should be repeated close to term
      to check on the estimated fetal weight to rule out macrosomia. Obese pregnant
      women are screened for gestational diabetes around 24 to 28 weeks. During the
      second half of pregnancy, one needs to closely watch for signs and symptoms of
      pregnancy-induced hypertension. Once in labor, an early anesthesia consultation
      is highly recommended irrespective of delivery mode. When Cesarean section is
      performed, many obstetricians prefer an incision above the pannus to avoid skin
      infection. However, the incision should be decided upon the discretion of the
      surgeon. Peripartum, special attention is given to avoid thromboembolism by using
      compression stockings and early ambulation.

PMID- 18824818
TI  - Bariatric surgery: is it right for your patient?
AB  - Obesity has become an international problem with the population rapidly gaining
      weight. The optimal treatment is diet and exercise; however, it is rarely
      effective in very heavy patients. Diet medications are also ineffective for these
      individuals. Because of its success in causing weight loss and controlling
      comorbid conditions, bariatric surgery has become increasingly popular. The most
      accepted operations are the Roux-en-Y gastric bypass (RYGB) and the laparoscopic
      adjustable band procedure. Both procedures are associated with low morbidity and
      mortality. The gastric bypass results in rapid and substantial weight loss with
      rapid resolution of diabetes mellitus, sleep apnea, and other medical problems
      associated with obesity. Laparoscopic banding procedures achieve the same effect
      but more gradually and confer the advantage of very few complications. Careful
      patient selection is essential for the success of these procedures as is a
      structured follow-up process once the operations are performed.

PMID- 18824819
TI  - The Internet and safe, affordable medications-solutions for a broken health care
      system.

PMID- 18824820
TI  - Counterfeits and medication errors: keeping your patients safe.

PMID- 18824821
TI  - Commentary: why diagnose and treat ADHD in adults?
AB  - There are compelling reasons why primary care physicians concerned about the well
      being of their patients should strive to become competent in recognizing the
      symptoms of attention-deficit/hyperactivity disorder (ADHD). Despite lingering
      social controversy, the existence of ADHD among a portion of the adult population
      is well accepted among medical experts. Attention deficit/hyperactivity disorder
      in adulthood meets formal validity criteria established for medical disorders. An
      estimated 4% to 5% of the adult population is impaired by ADHD. However,less than
      one-quarter of these adults have been diagnosed as having ADHD

PMID- 18824822
TI  - A practical guide to recognition and diagnosis of ADHD in adults in the primary
      care setting.
AB  - Attention-deficit/hyperactivity disorder (ADHD) is commonly perceived as a
      childhood disorder, but ADHD symptoms can persist into adulthood. The symptoms,
      deficits, and consequences associated with adult ADHD can have a profound impact
      on the daily lives of patients and their families. Self-awareness of ADHD
      symptoms can sometimes be difficult for adults who have lived with these symptoms
      since childhood. Attention-deficit/hyperactivity disorder is highly comorbid with
      other psychiatric disorders, and physicians should maintain a high index of
      suspicion and integrate screening for ADHD when they feel that psychiatric
      evaluation is indicated in their adult patients. Attention-deficit/hyperactivity
      disorder can be screened for in as little as 3 to 5 minutes with a variety of
      self-report or physician-implemented scales. An accurate diagnosis of ADHD in
      adults requires a comprehensive clinical interview that reviews representative
      symptoms starting in childhood that continue to cause impairment into adulthood.
      It is often helpful to interview or obtain information from family, friends,
      coworkers, or school records. With increasing understanding of ADHD in adults,
      the recent development of adult-specific diagnostic scales promises further
      improvement in the standard of care for this disorder. Appropriate treatment of
      ADHD in adults can provide dramatic symptomatic improvement with some of the
      largest treatment effects of any medical condition.

PMID- 18824823
TI  - Attention-deficit/hyperactivity disorder in adults: evidence-based
      recommendations for management.
AB  - Attention-deficit/hyperactivity disorder (ADHD) is associated with impairments in
      educational, occupational, neuropsychological, and social functioning in adults.
      Successful diagnosis and treatment of the disorder in adults can be a challenge
      because recent and integrative clinical guidelines are lacking and diagnostic
      criteria are based on making a retrospective diagnosis of childhood-onset ADHD.
      To develop evidence-based recommendations for the treatment of ADHD in adults,
      the scientific literature was reviewed, including primary clinical studies, meta
      analyses, and available clinical guidelines. Studies show that stimulant therapy
      is highly effective and safe in the management of ADHD in adults, with similar
      response rates to those reported in children at doses that are equivalent on a
      mg/kg basis. Long-acting stimulants, such as OROS methylphenidate (OROS MPH,
      Concerta), dexmethylphenidate (d-MPH, Focalin), and mixed amphetamine salts
      extended release (MAS XR, Adderall XR), have durations of action of up to 10 to
      12 hours, which permit once-daily dosing. For adults with ADHD who do not respond
      to stimulant therapy or who have a comorbid condition in which a stimulant is
      contraindicated, the nonstimulant atomoxetine (Strattera) may be an appropriate
      alternative. For many adults, cognitive-behavioral therapy in addition to
      pharmacotherapy may improve treatment response. Attention-deficit/hyperactivity
      disorder medications may increase blood pressure and heart rate in adults, so
      patients should be monitored.

PMID- 18824824
TI  - Attention-deficit/hyperactivity disorder in adults: recognition and diagnosis of
      this often-overlooked condition.
AB  - Attention-deficit/hyperactivity disorder (ADHD) in adults poses diagnostic
      challenges. How does it differ from ADHD in children? What are the necessary
      characteristics to make the diagnosis? What features of a patient's behavior are
      suggestive of ADHD? Which psychiatric disorders can mask its presence? What is
      the most important diagnostic procedure? This article provides insight into the
      behavior patterns of adults with ADHD, presents useful tools for identifying
      unrecognized cases, and includes several vignettes of actual patients.

PMID- 18824825
TI  - Global issues related to the impact of untreated attention-deficit/hyperactivity
      disorder from childhood to young adulthood.
AB  - Attention-deficit/hyperactivity disorder (ADHD) is a common, chronic, and costly
      disorder, with an impact that can span from preschool into adulthood. There are
      safe and effective therapies that can manage and help prevent many of the
      associated negative outcomes of ADHD, but treatment rates are far from optimal
      and considerable obstacles exist in achieving satisfactory treatment adherence.
      Individuals with untreated ADHD, their families, and other caregivers must be
      made aware of the impact that this disorder may have on them at every stage of
      life and, correspondingly, the improved outcomes that can be achieved with the
      successful management of ADHD.

PMID- 18824826
TI  - Special issues in the diagnosis and treatment of ADHD in adolescents.
AB  - Attention-deficit/hyperactivity disorder (ADHD) is a common disorder among
      adolescents but can be a challenge to diagnose in this population for several
      reasons. Obvious symptoms of hyperactivity and impulsivity are displayed less
      frequently than in younger children. Direct observation by potential raters is
      more limited because adolescents spend less time with parents and usually have
      multiple teachers throughout the day. Also, adolescents often suffer from
      psychiatric comorbidities, which affect the presentation of ADHD and can confound
      the diagnosis. Similarly, impaired social skills and academic performance may
      result from this disorder or for other reasons. These difficulties underscore the
      importance of a careful and comprehensive assessment that includes parent-,
      teacher-, and self-reported measures of functioning in several environments,
      including school, home, and work. Because ADHD is chronic and usually impairing
      in several domains (eg, social skills, academic performance, family relations,
      emotional health, driving), adequate treatment is essential. However, there are
      relatively few treatment studies in adolescents. Stimulant agents are well
      established as first-line medication treatment for both school-aged children and
      adults. Existing data support that this is also the case with adolescents.
      Specifically, both an extended-release formulation of methylphenidate, osmotic
      release oral system (OROS MPH; CONCERTA) and a mixed amphetamine salts extended
      release (MAS XR; Adderall XR) have demonstrated efficacy and safety in reducing
      the core symptoms of ADHD in well-designed, multisite, placebo-controlled, double
      blind trials. Additional research is needed to further refine diagnostic and
      assessment tools in the adolescent population.

PMID- 18824827
TI  - Onset of efficacy of long-acting psychostimulants in pediatric attention
      deficit/hyperactivity disorder.
AB  - BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) adversely impacts the
      educational achievement, mood and emotion processing, and interpersonal
      relationships of children and adolescents. Effective treatments include a number
      extended-release (ER) methylphenidate-(MPH) and amphetamine-based drugs. Some
      formulations release a comparatively larger bolus after dosing and can result in
      different onset and duration of efficacy. OBJECTIVE: Provide an evidence-based
      description of the time course of efficacy of psychostimulant medications used in
      ADHD treatment of children and adolescents. DATA SOURCES: A literature search
      from 1998 to 2008 was conducted using a MEDLINE database and the keywords
      "attention-deficit/hyperactivity disorder," "extended-release," "sustained
      release," "methylphenidate," "amphetamine," "randomized," "controlled,"
      "placebo," "efficacy," "time course," and "classroom study." DATA EXTRACTION:
      Selection criteria included randomized, blinded, placebo- or active comparator
      controlled clinical studies that evaluated an ER formulation of a psychostimulant
      treatment for ADHD in at least 30 children and adolescents aged 6 to 17 years.
      STUDY SELECTION: Eighteen clinical trials met the chosen criteria and evaluated:
      d, l-MPH, long-acting (d, l-MPH-LA); d, l-MPH-OR; d, l-MPH-CD (MCD); d-MPH-ER;
      MPH transdermal system (MTS); mixed amphetamine salts, ER (MAS-XR); and
      lisdexamfetamine dimesylate (LDX). DATA SYNTHESIS: Onset of efficacy was earliest
      for d-MPH-ER at 0.5 hours, followed by d, l-MPH-LA at 1 to 2 hours, MCD at 1.5
      hours, d, l-MPH-OR at 1 to 2 hours, MAS-XR at 1.5 to 2 hours, MTS at 2 hours, and
      LDX at approximately 2 hours. Duration of efficacy for each treatment was: MCD
      7.5 hours; d, l-MPH-LA 8 to 12 hours; and 12 hours for MTS, d-MPH-ER, d, l-MPH
      OR, MAS-XR, and LDX. However, data should be interpreted with caution given the
      different trial designs and assessment time points. CONCLUSIONS: d-MPH-ER has the
      earliest onset of efficacy at 0.5 hours postdose, and MTS, d-MPH-ER, d, l-MPH-OR,
      MAS-XR, and LDX have a long duration of action at 12 hours postdose. Clinicians
      should consider differences in the onset of efficacy of each drug in the context
      of individual patient needs.

PMID- 18824828
TI  - Effect of lisdexamfetamine dimesylate on parent-rated measures in children aged 6
      to 12 years with attention-deficit/hyperactivity disorder: a secondary analysis.
AB  - To evaluate the efficacy of lisdexamfetamine dimesylate (LDX) in school-aged
      children with attention-deficit/hyperactivity disorder (ADHD), using the Conners'
      Parent Rating Scale, Revised Short Version (CPRS-R:S) and its subscales. METHODS:
      This was a secondary post hoc analysis of data from a placebo-controlled, double
      blind, parallel-group, forced dose-escalation trial. Boys and girls aged 6 to 12
      years with a primary diagnosis of ADHD were randomly assigned to LDX (30, 50, or
      70 mg/d) or placebo. Improvement on the CPRS-R:S and its subscales (ADHD Index,
      hyperactivity, oppositional, and cognition) at 10:00 AM, 2:00 PM, and 6:00 PM was
      analyzed. Safety assessments included the identification of adverse events and
      were conducted throughout the study. RESULTS: Of the 290 patients randomized, 285
      were included in the intent-to-treat population. Parents noted significant
      improvements at all 3 assessment times on the CPRS-R:S total score and for the
      CPRS-R:S ADHD Index, hyperactivity, and cognition subscales, regardless of the
      subject baseline disease severity. For the CPRS-R:S oppositional subscale,
      significant improvement was noted at 10:00 AM and 2:00 PM (P < 0.01), and
      overall, significant improvement occurred in subjects who were more severely ill
      at baseline. The tolerability of LDX was comparable to that of other stimulants.
      CONCLUSION: Once-daily treatment with LDX was associated with significant
      improvement in parent-rated assessments of ADHD-related behavior throughout the
      day at approximately 10:00 AM, 2:00 PM, and 6:00 PM. Lisdexamfetamine dimesylate
      was effective and well tolerated in this study population of children aged 6 to
      12 years with ADHD.

PMID- 18824829
TI  - The optimal treatment of carotid atherosclerosis: a 2008 update and literature
      review.
AB  - Carotid and cerebrovascular disease have major public health implications given
      the associated morbidity and mortality. However, the best treatment for this
      disease is uncertain. Carotid endarterectomy has proven useful in primary and
      secondary prevention of strokes for patients with significant internal carotid
      artery stenoses. Many patients are considered at high risk for such surgical
      procedures and therefore have relatively few treatment options. Carotid stenting
      is currently being investigated as an alternative therapeutic intervention for
      these patients. This article reviews the literature pertaining to carotid
      intervention and its current status in 2008.

PMID- 18824830
TI  - Bronchiectasis in adults: a review.
AB  - Bronchiectasis is characterized by permanent, abnormal dilation of the bronchi
      with chronic inflammation and infection. Bronchiectasis is either caused by or
      associated with several systemic disorders, and in a significant number of cases,
      the underlying etiology remains unidentified and is subsequently referred to as
      idiopathic. The clinical course is characterized by chronic cough with purulent
      sputum associated with acute exacerbations. Patients may develop progressive
      decline in pulmonary function due to ongoing infection, inflammation, and
      destruction of bronchi if a delay in diagnosis and therapy occurs. With high
      resolution computed tomography, the confirmatory diagnosis of bronchiectasis can
      be made promptly and diagnostic work-up for etiology initiated. Identifying a
      specific etiology, when present, is critical for implementing appropriate
      treatment of the underlying cause. Whether a specific etiology can be identified
      or not, all cases of bronchiectasis require management that addresses infection,
      inflammation, and bronchial toilet.

PMID- 18824831
TI  - Posttraumatic stress disorder and aging.
AB  - The evidence base on effective treatments for posttraumatic stress disorder
      (PTSD) in the elderly population is scarce. The assessment and treatment of PTSD
      could pose a challenge for primary care providers and residents in training
      involved in treating PTSD in older adults. This article will review the
      epidemiology, the morbidity, the mortality, the biological perspective, the
      prognosis, and the psychosocial and pharmacological treatment options, in
      addition to the spiritual dimensions of PTSD and aging.

PMID- 18824832
TI  - Testosterone replacement therapy in hypogonadal men: assessing benefits, risks,
      and best practices.
AB  - Hypogonadism is a common condition, especially among older men, but often goes
      undiagnosed and untreated. It can be associated with a number of signs and
      symptoms that affect health and quality of life, including feelings of low energy
      and fatigue; decreased sex drive and performance; decreased muscle mass and
      strength; decreased bone mineral density; and increased body fat, particularly
      abdominal fat, a putative risk factor for metabolic syndrome and type 2 diabetes
      mellitus. The evidence supporting testosterone replacement therapy (TRT) in
      improving these and related conditions is strong and consistent for body
      composition and sexual function; moderately consistent for bone mineral density;
      inconsistent for insulin sensitivity, glycemic control, and lipid profiles; and
      weak and inconsistent for mood and cognitive function. The concern of some
      physicians about the potential for TRT to stimulate prostate cancer is not
      supported by decades of data accumulated to date, though studies of longer
      duration (eg, 10 years or more) would be even more convincing. Other research
      needs are discussed. As the front line of health care delivery, primary care
      physicians need to be vigilant in diagnosing and treating symptomatic
      hypogonadism. Based on current guidelines, we recommend assessing testosterone
      levels when an adult man exhibits signs of hypogonadism, and as part of normal
      medical screening in men starting at age 40 to 50 years, to establish a baseline.
      A physician should discuss the possibility of TRT with symptomatic patients who
      have a serum total testosterone level < 300 ng/dL. If TRT is initiated, a
      patient's response and adverse events should be assessed every 3 to 6 months, and
      therapy adjusted accordingly.

PMID- 18824833
TI  - What matters to patients and physicians when considering biologic therapy for
      rheumatoid arthritis.
AB  - OBJECTIVES: Patients and rheumatologists have a number of options to consider for
      the treatment of rheumatoid arthritis (RA), including biologic response modifier
      (BRM) therapy and diseasemodifying antirheumatic drugs (DMARDs). The objective of
      this study was to identify the considerations that are most important to patients
      and rheumatologists when deciding to initiate BRM therapy for RA. METHODS: An
      online survey was conducted by Harris Interactive (Rochester, NY) and completed
      in January 2007. Patients receiving BRMs were asked to rank their considerations
      in initiating BRM therapy, patients receiving DMARDs were asked to rank their
      considerations in switching to or initiating BRM therapy, and rheumatologists
      were asked to rank their considerations in prescribing BRM therapy. Participants
      arranged the following 9 factors from most to least important: efficacy,
      safety/side effects, years on market, physician's experience with product,
      physician's personal preference, method of administration, dosing frequency, cost
      (out of pocket), and patient support programs. RESULTS: A total of 400
      rheumatologists and 729 patients were surveyed (BRMs, n = 504; DMARDs, n = 225).
      The following factors were ranked consistently high across groups: safety (ranked
      first, first, and second for BRM patients, DMARD patients, and rheumatologists,
      respectively), efficacy (second, fourth, and first, respectively), and
      physician's experience with the drug (third for all 3 groups). Years on market
      (ranked seventh, sixth, and seventh, respectively) and availability of patient
      support groups ranked consistently low. CONCLUSIONS: When considering BRM therapy
      for RA, the 3 most important factors for patients and physicians are safety,
      efficacy, and the physician's experience with the product.

PMID- 18824834
TI  - Treatment options for insomnia--pharmacodynamics of zolpidem extended-release to
      benefit next-day performance.
AB  - BACKGROUND: Insomnia can manifest as difficulty in falling asleep, in maintaining
      sleep throughout the night, or waking up too early, with symptoms often
      unpredictably changing over time. Pharmacologic options for insomnia treatment
      include prescription hypnotics, such as gamma-amino butyric acid-receptor
      agonists, sedating antidepressants, over-the-counter antihistamines, melatonin
      receptor agonists, and alternative therapies. A concern with insomnia medications
      is the risk of next-day residual effects, which can impair memory and ability to
      perform certain tasks, such as driving, and may increase the risk of accidents
      and falls, especially in the elderly. OBJECTIVES: To describe the impact of
      current insomnia treatments on next-day performance. RESULTS: The longer-acting
      benzodiazepines are associated with next-day "hangover" effects and, as a result,
      have been largely replaced by agents in the nonbenzodiazepine class, which
      typically have shorter half-lives. The hypnotic, sedative activities of these
      classes of drugs depend on variations in binding characteristics to the alpha1
      subunit of the gamma-amino butyric acidA-receptor, which inhibits neuronal
      activity in broad areas of the brain and is found in areas of the brain
      responsible for sleep/wakefulness and sedation. However, nonbenzodiazepines with
      a rapid onset of action and short half-life have shown limited efficacy for
      maintaining sleep throughout the night. These properties have contributed to the
      development of modified-release formulations. Zolpidem extended-release is a
      bilayer tablet that retains the fast onset of action of its parent compound
      zolpidem while extending the duration of hypnotic activity, owing to a slower
      release portion of the tablet. CONCLUSIONS: Based on clinical evidence, the risk
      of residual next-day effects of zolpidem extended-release is limited, mainly due
      to the similarly short half-life in its extended-release formulation.

PMID- 18824835
TI  - Pen devices to improve patient adherence with insulin therapy in type 2 diabetes.
AB  - As the incidence of type 2 diabetes mellitus increases, the related health and
      economic burdens also increase as the majority of these patients with type 2
      diabetes do not achieve adequate glycemic control. There are several barriers to
      effectively managing type 2 diabetes, some of which can be overcome by insulin
      pen devices, thereby improving treatment acceptance/adherence and clinical
      outcomes in the primary care setting. Studies have shown that patients
      significantly prefer insulin pen devices compared with vial and syringe, and that
      the use of pen devices results in improved patient adherence to therapy, fewer
      hypoglycemic episodes, and reduced associated health care costs.

PMID- 18824836
TI  - Puzzles in practice. Pyomyositis.

PMID- 18824837
TI  - A genomic view on nitrogen metabolism and nitrogen control in mycobacteria.
AB  - Knowledge about nitrogen metabolism and control in the genus Mycobacterium is
      sparse, especially compared to the state of knowledge in related actinomycetes
      like Streptomyces coelicolor or the close relative Corynebacterium glutamicum.
      Therefore, we screened the published genome sequences of Mycobacterium smegmatis,
      Mycobacterium tuberculosis, Mycobacterium bovis, Mycobacterium avium ssp.
      paratuberculosis and Mycobacterium leprae for genes encoding proteins for uptake
      of nitrogen sources, nitrogen assimilation and nitrogen control systems,
      resulting in a detailed comparative genomic analysis of nitrogen metabolism
      related genes for all completely sequenced members of the genus. Transporters for
      ammonium, nitrate, and urea could be identified, as well as enzymes crucial for
      assimilation of these nitrogen sources, i.e. glutamine synthetase, glutamate
      dehydrogenase, glutamate synthase, nitrate reductase, nitrite reductase, and
      urease proteins. A reduction of genes encoding proteins for nitrogen transport
      and metabolism was observed for the pathogenic mycobacteria, especially for M.
      leprae. Signal transduction components identified for the different species
      include adenylyl- and uridylyltransferase and a P(II)-type signal transduction
      protein. Exclusively for M. smegmatis, two homologs of putative nitrogen
      regulatory proteins were found, namely GlnR and AmtR, while in other
      mycobacteria, AmtR was absent and GlnR seems to be the nitrogen transcription
      regulator protein.

PMID- 18824838
TI  - Cell surface immobilization of GABAA Rs in cerebellar granule cells depends on
      the M3/M4 cytoplasmatic loop of the alpha 1 subunit.
AB  - Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the
      vertebrate brain. The localization of GABA receptors type A (GABA(A)Rs) at
      strategically located domains of the neuronal membrane is of vital importance for
      fast inhibitory synapse transmission efficacy. We have shown before that the
      lateral mobility of GABA(A)Rs depends on subunit composition of the complex. To
      study the lateral mobility of GABA(A)Rs in living, cultured neurons, we
      transfected cerebellar granule cells with either the complete alpha1 GABA(A)R
      subunit or with a truncation of the alpha1 subunit that lacks the major
      intracellular loop (M3/M4). We examined the location and lateral mobility of
      receptors containing both versions of the alpha1 subunit in living neurons. From
      fluorescence recovery after photobleaching experiments we present novel evidences
      that the intracellular M3/M4 loop of the alpha1 subunit restricts the lateral
      mobility of GABA(A)Rs when expressed in neurons. In addition, our
      immunocytochemical studies suggested that receptors containing the truncated
      subunit seem to be unable to reach synaptic localizations. Here we show for the
      first time that the alpha1 intracellular loop (M3/M4) domain has a relevant role
      in controlling the lateral mobility of GABA(A)Rs in neurons, and we believe that
      this is a novel and important contribution in neurobiology of GABA(A) receptors.

PMID- 18824839
TI  - The bovine kidney as an experimental model in urology: external gross anatomy.
AB  - The objective of this work was to obtain and record detailed and accurate
      measurements of the bovine kidney and to compare these new data with findings in
      humans. Thirty-eight bovine kidneys were used. The total number of lobes, along
      with the number of lobes located in the cranial polar, caudal polar and hilar
      regions, were recorded. Several measurements of the kidneys were made and
      evaluated. The hilar region presents the greatest length (mean of 76.87 mm) of
      the 3 renal regions of the kidney. The large area of the bovine renal hilus could
      make access to hilar structures easier than in the human kidney. The coefficient
      of variation for renal length was small (8.14%), while the coefficient of
      variation for the lobar number was high (26.82%). The number of renal lobes
      ranged from 13 to 35, with a mean of 20.62. The hilar region presents the highest
      number of lobes, while the cranial pole presents the lowest. The number of lobes
      in the cranial and caudal poles increases with the width of these regions. This
      is different from the hilar region, in which the lobar number increases with the
      length of the hilus. These data indicate that the adult bovine kidney can be used
      as a model for certain urologic procedures, but researchers must be aware that
      there are some major differences between the adult bovine kidney and the human
      kidney, as indicated by the data reported in this paper.

PMID- 18824840
TI  - Organ-specific changes in the expression of mannose-6-phosphate receptors during
      postnatal development in rats.
AB  - The significance of the coexistence of 2 mannose-6-phosphate receptors (MPRs) in
      most cell types still remains poorly understood. In this study, expression of the
      cation-dependent MPR (CD-MPR) and the cation-independent MPR (CI-MPR) was
      measured by Western blot in rat organs at 3 ages, i.e. in newborn and 10- and 90
      day-old rats. It was observed that expression of the CI-MPR tends to diminish
      from newborns to adults in 5 of the 6 organs studied, whereas the CD-MPR did not
      show a clear tendency over time. In pancreas, conversely, both MPRs increased
      progressively from newborns to adults. The activity of 2 acid hydrolases was also
      measured at the different ages, and a low correlation was found with the
      expression of the 2 MPRs. With the exception of the pancreas, it is possible that
      the CI-MPR is mostly occupied with the clearance of insulin-like growth factor-II
      at early stages of development, and that later both MPRs may participate in the
      maturation of the lysosomal apparatus. We propose that in the pancreas, both
      receptors may be involved in increasing the proteolytic activity of this exocrine
      gland during postnatal development.

PMID- 18824841
TI  - Detection of humoral immune responses against WT1 antigen in patients affected by
      different hematological malignancies.

PMID- 18824842
TI  - In vitro effects of the farnesyltransferase inhibitor tipifarnib on
      myelodysplastic syndrome progenitors.
AB  - BACKGROUND: Farnesyltransferase inhibitors (FTIs) target proteins needing
      prenylation for functioning. Tipifarnib (Zarnestra), a potent and specific
      inhibitor of farnesyltransferase, showed considerable activity in phase I and II
      studies in myelodysplastic syndrome (MDS), but the optimal regimen achieving high
      response rates with minor myelosuppression remains to be determined.
      Additionally, a direct effect on purified human MDS progenitors has not yet been
      shown. METHODS: MDS and normal CD34+ cells isolated by using immunomagnetic beads
      were plated for short-term cultures in semisolid media or liquid cultures for
      flow-cytometric assessment of apoptosis in the presence of either DMSO or various
      FTI concentrations. RESULTS: Tipifarnib exerted selective in vitro toxicity
      against clonal MDS hematopoiesis at concentrations less than 10 nM the effect
      being more prominent in white cell progenitors. This action was not due to
      apoptosis induction as both normal and MDS progenitors displayed equivalent DiOC3
      and annexin V expression up to 72 h after exposure to tipifarnib. CONCLUSION: The
      leukemic clone is more susceptible in tipifarnib than normal progenitors. Since
      myelosuppression represents the main obstacle in the clinical use of tipifarnib
      in MDS, further reduction of the currently employed dose will potentially result
      in a more tolerable regimen without compromising its antileukemic action.

PMID- 18824843
TI  - Familial Mediterranean fever gene as a possible modifier of Sweet syndrome with
      chronic myelogenous leukemia.
AB  - Sweet syndrome is a multisystem inflammatory disorder characterized by acute
      fever, as well as painful erythematous plaques infiltrated with mature
      neutrophils in the absence of vasculitis. The pathogenesis of the disease has not
      yet been clarified, although several proinflammatory cytokines have been reported
      to be involved in the disease process. We describe here a patient clinically
      diagnosed with Sweet syndrome with chronic myelogenous leukemia. The mutational
      analysis of the patient revealed a compound heterozygous E148Q/R202Q mutation in
      exon 2 of MEFV gene, which is a causative gene for familial Mediterranean fever.
      This is the first report to describe MEFV gene mutations in Sweet syndrome. Our
      results suggest that Sweet syndrome may be mediated though similar inflammatory
      mechanisms to those of familial Mediterranean fever.

PMID- 18824844
TI  - Endogenous hepatocyte growth factor attenuates inflammatory response in glycerol
      induced acute kidney injury.
AB  - BACKGROUND: Hepatocyte growth factor (HGF) is overexpressed after acute kidney
      injury (AKI). The aim of this study was to evaluate the role of endogenous HGF in
      the progression of the inflammatory response in glycerol-induced AKI (Gly-AKI) in
      rats. METHODS: Renal and systemic HGF expressions were evaluated during the
      development of Gly-AKI. Subsequently, the blockade of endogenous HGF was analyzed
      in rats treated with anti-HGF antibody concomitant to glycerol injection.
      Apoptosis, cell infiltration and chemokine and cytokine profiles were
      investigated. RESULTS: We detected an early peak of renal and plasma HGF protein
      expressions 3 h after glycerol injection. The pharmacological blockade of the
      endogenous HGF exacerbated the renal impairment, the tubular apoptosis, the renal
      expression of monocyte chemoattractant protein-1 and the macrophage, CD43+, CD4+
      and CD8+ T lymphocytes renal infiltration. The analysis of mRNA expressions of
      Th1 (t-bet, TNF-alpha, IL-1beta) and Th2 (gata-3, IL-4, IL-10) cytokines showed a
      Th1-polarized response in Gly-AKI rats that was aggravated with the anti-HGF
      treatment. CONCLUSION: Endogenous HGF attenuates the renal inflammatory response,
      leukocyte infiltration and Th1 polarization after glycerol injection. The control
      of cellular immune response may partly explain the protective effect of
      endogenous HGF in the development of Gly-AKI.

PMID- 18824845
TI  - Correlates of N-terminal prohormone brain natriuretic peptides in African
      Americans with hypertensive chronic kidney disease: the African American Study of
      Kidney Disease and Hypertension.
AB  - BACKGROUND/AIMS: The N-amino-terminal fragment of the prohormone B-type
      natriuretic peptide (NT-proBNP) is a marker of cardiac stress and elevated levels
      are indicative of heart failure. Few correlates of NT-proBNP levels have been
      identified in persons with moderate chronic kidney disease (CKD), and data from
      those without heart failure and from African Americans are especially limited.
      METHODS: The African American Study of Kidney Disease and Hypertension (AASK)
      enrolled nondiabetic African Americans with hypertensive kidney disease
      (glomerular filtration rate [GFR] = 20-65 ml/min/1.73 m(2)) and no evidence of
      clinical heart failure. NT-proBNP was measured in 982 AASK participants. RESULTS:
      In unadjusted analyses, GFR (r = -0.39; p < 0.001), hematocrit (r = -0.21; p <
      0.001) and body mass index (BMI; r = -0.07; p = 0.04) were inversely correlated,
      and systolic blood pressure (r = 0.30; p < 0.001) and log UPCR (r = 0.32; p <
      0.001) were positively correlated with log NT-proBNP levels. After adjustment for
      potential confounders, lower GFR and hematocrit and higher systolic blood
      pressure and protein:creatinine ratio remained significantly associated with
      higher NT-proBNP. CONCLUSION: Lower GFR and hematocrit, and higher urinary
      protein excretion may be associated with volume expansion in CKD. These results
      suggest that these processes are associated with increased NT-proBNP in CKD and
      may play a role in the development of heart failure.

PMID- 18824846
TI  - Iron supplementation during treatment with erythropoiesis-stimulating agents for
      cancer-related anemia.
AB  - Unresponsiveness to erythropoiesis-stimulating agents is a major limitation to
      the treatment of chemotherapy-related anemia. This is often related to a
      disregulation of iron metabolism leading to functional iron deficiency. However,
      the use of iron supplementation during treatment with erythropoiesis-stimulating
      agents has not been as rigorously pursued in anemic patients with cancer as it
      has in chronic kidney disease. In this article, we review and discuss the role of
      iron supplementation in the setting of chemotherapy-related anemia in view of
      recently published clinical trials addressing this issue.

PMID- 18824847
TI  - Molecular imaging suggests efficacy of bevacizumab beyond the second line in
      advanced colorectal cancer patients.
AB  - We report the clinical history of a female affected by advanced colorectal cancer
      (CRC). The patient was treated with five subsequent therapeutic schedules
      (FOLFIRI, FOLFOXIRI, FOLFIRI, FOLFOX4, FOLFOX4 plus cetuximab) because of the
      progression of the disease. The sixth treatment was bevacizumab in combination
      with 5-fluorouracil and irinotecan (FOLFIRI). The CT scan and the FDG-PET/CT
      performed 3 months after the beginning of the treatment showed that some, even if
      not all, lesions had a reduction of both size and metabolic activity. After the
      second revaluation the disease progressed. This short report suggests that the
      response of CRC to antiangiogenetic therapy may also occur after several
      unsuccessful antineoplastic treatments. Different biological features may explain
      the nonhomogeneous objective response of the metastatic lesions. Molecular
      imaging techniques seem to be mandatory in the era of tailored therapy since it
      is useful to have an in vivo 'biological picture' of the neoplastic disease.

PMID- 18824848
TI  - Loss of bladder sensation following taxane therapy.

PMID- 18824849
TI  - Comparison of the Sensititre YeastOne colorimetric antifungal panel with the
      modified Clinical and Laboratory Standards Institute broth microdilution (M38-A)
      method for antifungal susceptibility testing of dermatophytes.
AB  - BACKGROUND: To compare the susceptibility of different dermatophyte species to
      itraconazole (I), fluconazole (F) and voriconazole (V) by the modified reference
      (microdilution, CLSI M38-A) and the colorimetric method Sensititre YeastOne. The
      microdilution method is not very practical for use in routine susceptibility
      testing in the clinical laboratory, thus necessitating the use of other methods.
      METHODS: We studied a total of 46 dermatophyte strains isolated from clinical
      specimens. The microdilution reference susceptibility testing was performed
      following the CLSI M38-A document, using I, F and V drugs. The MIC were defined
      as the lowest drug concentration that produced 100% (I and V) and 50% inhibition
      (F) after 72 h incubation at 35 degrees C. The Sensititre MIC were detected by a
      change in color from pink to blue or purple. RESULTS: Agreement levels between
      the 2 methods (+/-2 dilutions) for I, F and V were 30, 53.3 and 83.3%, 0, 12.5
      and 66.6% and 37.5, 44.4 and 75% for Trichophyton mentagrophytes, Trichophyton
      rubrum and Microsporumgypseum, respectively. The MIC(50/90) (mg/l) of I, F and V
      for T. mentagrophytes were 0.25/0.5, 16/64 and 0.12/0.25 by the microdilution
      method and 0.016/0.06, 8/16 and 0.03/0.06 by the Sensititre method. The MIC for
      I, F and V for T. rubrum were 0.25/1, 8/64 and 0.25/0.5 by the microdilution and
      0.008/0.03, 2/8, 0.016/0.03 by the Sensititre method. For M. gypseum, MIC were
      0.5/1 (I), /256 (F) and 0.25/1 (V) as well as 0.016/0.25 (I), 16/256 (F) and
      0.06/0.25 (V) by the microdilution and Sensititre methods, respectively.
      CONCLUSIONS: The MICs obtained were lower by the Sensititre than the
      microdilution method. The best correlation between both methods was obtained for
      V in T. mentagrophytes (>80%), but was low for T. rubrum. Although the Sensititre
      method is easy to use in a clinical laboratory, it shows poor agreement with the
      reference method for dermatophytes.

PMID- 18824850
TI  - Somatostatin elevates topoisomerase II alpha and enhances the cytotoxic effect of
      doxorubicin on gallbladder cancer cells.
AB  - BACKGROUND: Gallbladder cancer is a common and lethal digestive malignancy which
      is nonsensitive to routine chemotherapy. Doxorubicin (DOX) is one of the major
      chemotherapeutic drugs for patients with gallbladder cancer. We tried to evaluate
      if combined use of somatostatin (SST) and DOX could have synergistic effect in
      the treatment of gallbladder cancer. METHODS: Cells from the human gallbladder
      cancer cell line GBC-SD were treated with SST. Cell cycle analysis was determined
      by flow cytometry. Western blot analysis was performed to determine the protein
      levels of topoisomerase IIalpha (Topo IIalpha) after SST treatment. RT-PCR was
      utilized to detect SST receptors in GBC-SD cells. Finally, the chemotherapeutic
      effect of DOX combined with SST treatment on cellular growth was measured by MTT
      assay. RESULTS: SST could induce cell cycle arrest in S phase and upregulate Topo
      IIalpha expression in GBC-SD cells. GBC-SD cells expressed all 5 subtypes of SST
      receptors. Finally, combined use of DOX with SST had a synergistic cytotoxic
      effect on GBC-SD cells. CONCLUSION: SST, a naturally occurring, nontoxic
      compound, may represent a novel adjuvant chemotherapeutic agent for patients with
      gallbladder cancer.

PMID- 18824851
TI  - In vitro and in vivo study of cell growth inhibition of simvastatin on chronic
      myelogenous leukemia cells.
AB  - BACKGROUND: Statins, a family of 3-hydroxy-3-methylglutaryl CoA (HMG CoA)
      reductase inhibitors, are being investigated for the therapy and prevention of
      cancers. Here we aimed to investigate the effects of simvastatin on chronic
      myelogenous leukemia (CML) cells in vitro and in vivo, and to elucidate the
      mechanisms. METHODS: Cell proliferation and cell cycle were measured after K562
      cells were incubated with simvastatin, and differentially expressed genes were
      determined by oligonucleotide microarray. Changes of 2 genes obtained by
      oligonucleotide microarray were validated by real-time RT-PCR, and
      immunohistochemistry was performed to determine expression of proliferating cell
      nuclear antigen (PCNA). Finally, a xenograft tumor model was constructed to
      evaluate the effects of simvastatin in vivo. RESULTS: Simvastatin could inhibit
      K562 cell proliferation, and the inhibition rate was approximately 30% after
      treatment with 20 mumol/l simvastatin for 48 h. Cell cycle was arrested in G(1)
      phase, as shown by flow cytometry results. Fifteen downregulated, 9 upregulated
      cell cycle-related genes and decreased PCNA protein were observed in the presence
      of simvastatin. Furthermore, simvastatin exhibited impairment of xenograft tumor
      growth in nude mice and also blocked cell cycle in G(1) phase. CONCLUSION:
      Simvastatin can inhibit CML cell proliferation in vitro and in vivo, and its
      mechanisms might be involved in cell cycle regulation.

PMID- 18824852
TI  - Intermittent versus continuous pantoprazole infusion in peptic ulcer bleeding: a
      prospective randomized study.
AB  - BACKGROUND AND AIM: Rebleeding has remained the most important determinant of
      poor prognosis in peptic ulcer bleeding. Gastric acid plays an important role in
      the pathogenesis of rebleeding. We aimed to compare the efficiency of
      intermittent and continuous pantoprazole infusion treatment on peptic ulcer
      rebleeding after endoscopic therapy. MATERIALS AND METHOD: In this prospective
      study, patients with active peptic ulcer bleeding or non-bleeding visible vessel
      were treated initially with endoscopic therapy. They were randomized to receive
      intermittent or continuous intravenous pantoprazole treatment. Rebleeding rate,
      duration of hospital stay, need for total blood transfusion and need for urgent
      surgery were compared among both groups. RESULTS: Rebleeding rate (6.1 vs. 8.3%),
      duration of hospital stay (4.17 vs. 4.41), need for total blood transfusion (2.18
      vs. 2.59) and need for urgent surgery (4.1 vs. 4.2%) were similar in intermittent
      and continuous pantoprazole infusion therapy groups, respectively. There was no
      bleeding-related death in either group. CONCLUSION: In patients with peptic ulcer
      bleeding, intermittent and continuous pantoprazole infusion after successful
      endoscopic therapy have comparable outcomes in reducing rebleeding. Both have
      similar effects on hospital stay, need for blood transfusion and urgent surgery.
      Intermittent administration has application and cost advantages over continuous
      infusion.

PMID- 18824853
TI  - Neurological words. Plexus.

PMID- 18824854
TI  - Hypertriglyceridemia and ischemic stroke.
AB  - There are no conclusive data regarding the association between dyslipidemia and
      the risk of ischemic stroke (IS). Clinical investigations have primarily focused
      on the association between elevated levels of low-density lipoprotein cholesterol
      and low levels of high-density lipoprotein cholesterol as stroke risk factors.
      Much less scientific attention has been aimed at elevated levels of
      triglycerides. Consequently the potential role of hypertriglyceridemia as an
      independent risk factor for IS remains controversial. However, accumulating
      evidence has shown that hypertriglyceridemia is associated with
      pathophysiological processes such as endothelial dysfunction, atherosclerosis and
      the production of a prothrombotic state, which could contribute to IS risk. The
      aim of this review is to critically analyze the contribution of
      hypertriglyceridemia to the occurrence of IS.

PMID- 18824855
TI  - Interferon-beta1b in multiple sclerosis: effect on progression of disability and
      clinical markers of treatment response.
AB  - There is limited long-term data on the effect of interferon-beta1b (IFN-beta1b)
      on disability progression in patients with multiple sclerosis (MS). There is also
      no reliable way of predicting individual responses to IFN-beta1b treatment. This
      prospective study investigated early clinical prognostic markers of disease
      activity and progression in 115 patients with relapsing-remitting MS (RRMS)
      treated with IFN-beta1b for almost 5 years. The study also compared progression
      of disability in IFN-beta1b-treated patients with a historic untreated cohort of
      MS patients (n = 44). The number of relapses in the first 2 years of MS and in
      the 2 years before treatment predicted an early relapse after IFN-beta1b
      treatment. The IFN-beta1b-treated group experienced a slower progression of
      disability than the untreated cohort, suggesting that IFN-beta1b treatment delays
      progression of disability in RRMS.

PMID- 18824856
TI  - Actigraphy--a useful tool for motor activity monitoring in stroke patients.
AB  - AIM: The aim of the present study was the evaluation of actigraphy as a tool to
      objectify the recovery process after motor paresis due to stroke. METHODS: The
      motor activity of both arms of patients suffering from stroke was actigraphically
      recorded at four different time points during the course of rehabilitation: 24-36
      h, 5-7 days, 3 months, and 6 months after stroke. RESULTS: Motor activity
      monitored by wrist-worn actigraphs located at the impaired side revealed an
      increase in activity between the first two time points and the subsequent ones.
      Additionally, actigraphic recordings showed lower total motor activity at the
      impaired side as compared to the nonimpaired side. A significant positive
      correlation was found between the actigraphically recorded motor activity and the
      results of the Scandinavian Stroke scale, the Barthel Index, the Rankin Scale
      Score and with the Motoricity Index during the 1st week, which corresponds to the
      time when neurological deficits were most pronounced. CONCLUSION: Our results
      suggest that actigraphy is a useful tool in the objective evaluation of motor
      activity after stroke. Moreover, actigraphy covers additional aspects that are
      not reflected by the usual stroke scales in a clinical situation.

PMID- 18824857
TI  - Clinical manifestations and management of acute thallium poisoning.
AB  - Clinical information regarding 3 patients diagnosed with acute thallium poisoning
      was collected and retrospectively analyzed. All 3 patients presented with severe
      burning pain in the lower limbs and the abdomen. Diffuse alopecia, hepatic
      dysfunction and Mees' lines in the digits of each limb were observed between 2
      and 3 weeks after onset. A physical examination demonstrated paresthesia of all 4
      limbs, but normal deep tendon reflexes. Blood and urine thallium concentrations
      were significantly elevated. Treatment was initiated using hemoperfusion,
      hemodialysis, potassium supplementation, oral laxatives and B complex
      supplementation. Clinical symptoms improved as blood and urine thallium
      concentrations decreased, although a residual sensory neuropathy remained. This
      study demonstrated that the primary clinical manifestations of acute thallium
      poisoning include gastrointestinal symptoms, polyneuropathy and dermatological
      changes. Hemoperfusion and hemodialysis may be effective treatments for acute
      thallium poisoning.

PMID- 18824858
TI  - Associations between serum selenium and total plasma homocysteine during the
      acute phase of ischaemic stroke.
AB  - BACKGROUND/AIMS: Risk of ischaemic stroke (IS) was associated with total
      homocysteine (tHCY). On the other hand, serum selenium (Se) exhibited anti-aging
      and cardiopreventive effects. Se and tHCY showed relationships in animals but
      these were contradictory or inconclusive in humans; therefore, we searched for
      such associations in acute IS. METHODS: Ninety-four participants aged around 47
      years were identified and 39 patients versus 46 healthy controls were analysed.
      Clinical, laboratory (blinded) and risk factor questionnaire methods were used.
      Comparison, correlation and multifactorial regression analyses were applied.
      RESULTS: IS patients were similar to controls concerning age and gender. IS was
      prevalent in the carotid system (76.9%); 82.1% had a subacute onset. IS patients
      expressed higher tHCY (14.65 +/- 9.79 micromol/l) and lower Se levels (1.3 +/-
      0.5 micromol/l). Twice as many IS patients (23%) had optimal Se levels of <1.01
      mumol/l. Subjects with hyperhomocysteinaemia (tHCY > or =15 micromol/l) showed
      lower Se levels during IS; Se accounted for 15.4% of tHCY variations (R = -0.393;
      p = 0.015) with unit change increasing tHCY by 8.25 units. Se remained predictive
      of tHCY levels after adjustments (vitamin B6, fibrinogen, triglycerides).
      CONCLUSIONS: Lower Se was observed during acute IS, being inversely associated
      with and predicting increased tHCY levels. Of note, there were more IS patients
      with suboptimal Se than controls.

PMID- 18824859
TI  - Short-term cognitive training improves mental efficiency and mood in patients
      with multiple sclerosis.
AB  - OBJECTIVES: The aim of this study was to evaluate a short-term non-specific home
      based 6-week cognitive training for its effect on neuropsychological deficits and
      depression. SUBJECTS AND METHODS: Cognitive and affective abilities of patients
      with MS were compared with healthy controls using an identical neuropsychological
      test battery. Re-testing was performed after 6 weeks of cognitive home-based
      training. RESULTS: Patients already showed cognitive deficits at baseline.
      Cognitive training resulted in a significant improvement in several skills, in
      particular with respect to visuoconstructive and figural long-term memory. In
      addition, prior depressed mood and quality of life improved in MS patients during
      the training period and remained up to 6 months. CONCLUSIONS: Our study
      corroborated the early appearance of neuropsychological deficits in MS. Mental
      training, although unspecific, lead to improvements with respect to attention and
      memory functions in patients, and to some degree in control subjects, which may
      last for more than 6 months.

PMID- 18824860
TI  - Food competition in a semi-free-ranging Cebus apella group.
AB  - The competitive regime faced by individuals is fundamental to modelling the
      evolution of social organization. In this paper, we assess the relative
      importance of contest and scramble food competition on the social dynamics of a
      provisioned semi-free-ranging Cebus apella group (n = 18). Individuals competed
      directly for provisioned and clumped foods. Effects of indirect competition were
      apparent with individuals foraging in different areas and with increased group
      dispersion during periods of low food abundance. We suggest that both forms of
      competition can act simultaneously and to some extent synergistically in their
      influence on social dynamics; the combination of social and ecological
      opportunities for competition and how those opportunities are exploited both
      influence the nature of the relationships within social groups of primates and
      underlie the evolved social structure.

PMID- 18824861
TI  - 'Padhar regime' - a low-dose magnesium sulphate treatment for eclampsia.
AB  - AIMS: To determine the recurrent convulsion rate using low-dose magnesium
      sulphate regime in eclampsia and to identify toxicity and complications with
      clinical parameters. METHODS: Prospective study with two different magnesium
      sulphate regimes in two slightly clinically different subgroups. Group A that
      came directly to our hospital and group B who had already received an injection
      of diazepam or Phenergan at the referring hospital. Group A received 10 g and
      group B 6 g loading dose of magnesium sulphate. Both groups received 4 g
      maintenance dose every 4 h. RESULTS: Out of 95 eclamptic patients, only one woman
      in group B had recurrent convulsion. All women maintained normal respiratory
      rates. 39 (41.1%) women had absent knee jerks on at least one occasion when the
      maintenance dose was omitted. Urinary output was more than 30 ml/h in 92 (96.8%)
      women. In 5 women, maintenance dose had to be augmented to 5 g as reflexes were
      exaggerated. CONCLUSION: The low-dose regime appears to control and prevent
      convulsions effectively in Indian women. Clinical monitoring appears to be
      sufficient. We hope to be able to reassure health professionals at primary and
      secondary level hospitals about the safety of magnesium.

PMID- 18824862
TI  - ADIDAC trial: analgesia with dexibuprofen versus ibuprofen in patients suffering
      from primary dysmenorrhea: a crossover trial.
AB  - BACKGROUND: Primary dysmenorrhea is estimated to affect 40-50% of menstruating
      young women. METHODS: Randomized, double-blind, 3-cycle crossover, active
      controlled clinical trial conducted in 102 outpatients. RESULTS: 102 patients
      entered the study and 77 were eligible for analyses. The mean (SD) age was 31.1
      (7.0) years, and the mean cycle duration was 28.1 days (1.89) with a mean
      menstrual phase of 5.3 days (1.28). 40.26% of patients reported moderate pain
      from dysmenorrhea, and the remaining 59.74% reported severe pain. Compared to
      ibuprofen 400 mg, both dexibuprofen doses (200 and 300 mg) showed a trend towards
      superiority for sum of pain intensity difference (sum of PID), PID and total pain
      relief. Furthermore, dexibuprofen 200 mg had a faster onset of action compared to
      the double dose of ibuprofen (p = 0.035). A dose-effect relationship could be
      demonstrated for dexibuprofen in this visceral pain model. Tolerability was
      similar across all treatments. CONCLUSIONS: In patients experiencing acute
      visceral pain as a result of primary dysmenorrhea, dexibuprofen was associated
      with a dose-dependent effective analgesia; this effect was at least equivalent to
      that of the double dose of ibuprofen. With its lower body-loading dose,
      dexibuprofen expands the alternatives available to treat this condition.

PMID- 18824863
TI  - Adrenarche: postnatal adrenal zonation and hormonal and metabolic regulation.
AB  - Adrenarche is the direct consequence of the organogenesis of the zona reticularis
      (ZR). Proliferation of cortical cells could take place in the outermost layers of
      the adrenal cortex. Cells could then migrate to differentiate the zona
      glomerulosa (ZG) and zona fasciculata (ZF) during fetal life, and the ZR during
      postnatal life. After adrenarche, there are detectable increases in circulating
      DHEA and DHEA-S. Adrenarche could result from an increase in 17,20-lyase activity
      of P450c17 secondary to high levels of cytochrome b(5) expression, and from a
      decrease in 3betaHSD2 expression along with an increase in the expression of
      SULT2A1 in the ZR. The GH-IGF system and insulin, among other factors, might also
      modulate adrenal androgen production. Furthermore, high concentrations of
      estradiol enhance basal and ACTH-stimulated DHEA-S production, while aromatase
      expression was observed in the human adrenal medulla but not in the ZR,
      suggesting that estrogens produced in the adrenal medulla might be involved in
      the regulation of androgen production in the ZR. Premature adrenarche might be
      associated with ovarian hyperandrogenism and polycystic ovarian syndrome in
      females, as well as with insulin resistance in both sexes. However, many
      questions remain, transforming adrenal androgens into markers of diseases
      important for human health.

PMID- 18824864
TI  - High-molecular-weight adiponectin and leptin levels in cord blood are associated
      with anthropometric measurements at birth.
AB  - AIMS: High-molecular-weight adiponectin (HMW-ad) is an active form of
      adiponectin. No information is available with respect to HMW-ad in neonates. The
      aims of this study were to examine whether HMW-ad is present in cord blood, to
      define the association between the concentrations of cord blood HMW-ad and
      leptin, and their correlation with anthropometric measurements of term neonates
      at birth. METHODS: Venous cord blood samples were obtained from 135 term healthy
      neonates (birth weight 2,261-4,164 g) born at Showa University Hospital. Total
      adiponectin (T-ad), HMW-ad and leptin levels were measured by ELISA. RESULTS: HMW
      ad levels were 14.9 +/- 5.8 microg/ml and the ratio of HMW-ad to T-ad was 0.49 +/
      0.15. In a multiple regression analysis, cord blood HMW-ad levels were a
      significant predictor of birth weight and birth length, and leptin level was a
      significant predictor of birth weight and birth weight to body length ratio.
      There was a significant relationship between concentrations of HMW-ad and leptin
      controlling for sex, gestational age and birth weight. CONCLUSION: These results
      show that HMW-ad exists as a half of T-ad in the cord blood. Leptin and HMW-ad
      may regulate synergistically fetal growth.

PMID- 18824865
TI  - Longitudinal growth during the first years of life: what is normal?
AB  - The anthropometric data of a longitudinal growth study on healthy infants,
      followed from birth until the age of 4 years and performed during 1995-1999 in
      The Netherlands, were used to analyze the general growth patterns in terms of
      height, weight and head circumference, based on z-scores, during the first 4
      years of life. The well-known phenomenon where each infant or child tends to
      decelerate or accelerate its growth velocity depending on its starting position
      on the reference curve is obvious in this study too. This phenomenon, known as
      the regression to the mean, is a strong phenomenon especially during the first
      year. Regression to the mean is calculated for the different age groups as
      factor. With the given alpha, it is possible to estimate the individual
      expectation of growth.

PMID- 18824866
TI  - Hashimoto's thyroiditis in Down's syndrome: clinical presentation and evolution.
AB  - AIM: It was the aim of this study to describe the presentation and clinical
      course of Hashimoto's thyroiditis (HT) in children with Down's syndrome (DS) in 2
      Scottish health regions. PATIENTS AND METHODS: We retrospectively analysed
      clinical, biochemical and thyroid antibody status in 38 patients with DS with HT
      diagnosed from 1989 to 2004. RESULTS: The sex distribution was similar (20 males,
      18 females), with a median age of 12.3 years (range 2.1-17.7). Of the 38 patients
      reviewed, 29 were identified by screening. A goitre was present in 6/38 patients.
      Thyroid antibodies were positive in 36/38 patients, negative in 1/38, and data
      were unavailable for 1/38. At presentation, 37/38 patients were hypothyroid:
      21/37 with compensated hypothyroidism (6 treated initially) and 16/37 with
      decompensated hypothyroidism (all treated). Of the 15/21 compensated patients who
      were untreated initially, only 3 remitted while 12 showed disease progression
      prompting treatment. In the decompensated group, 1/16 patient pursued a
      fluctuating course between hypo- and hyperthyroidism. The final patient, who was
      hyperthyroid at presentation, also showed marked fluctuation in thyroid function
      over a 5-year period. CONCLUSION: The natural history of HT in DS is unusual,
      with no female predominance and infrequent goitre in our cohort. While almost all
      patients required treatment eventually, clinicians should be aware that the
      disease may pursue a fluctuating course between hypo- and hyperthyroidism.

PMID- 18824867
TI  - The 'functional muscle-cartilage unit': a reasonable approach to describe a
      putative relationship between muscle force and longitudinal growth at the forearm
      in children and adolescents?
AB  - BACKGROUND: Several reports give evidence that the perichondral ossificiation of
      bone tubes (modeling) strongly depends on muscular forces in children and
      adolescents. The present analyses intend to investigate the hypothesis that
      muscular forces also partly determine enchondral ossification and, therefore,
      longitudinal growth of bone tubes. SUBJECTS AND METHODS: Analyses were based on a
      single cross-sectional investigation with peripheral quantitative computed
      tomography in 296 individuals (age 5-19 years) participating in the Dortmund
      Nutritional and Anthropometric Longitudinally Designed (DONALD) study. RESULTS:
      Forearm length (FL) was correlated with body height in gender-related subgroups
      of prepubertal and pubertal individuals (rs between 0.76 and 0.86). Cross
      sectional muscle area (MA) increased faster than FL and faster than cross
      sectional bone area (BA) close to the distal growth plate in puberty. Close to
      the growth plate, longitudinal growth was faster than perichondral ossification
      in females. The ratio MA/BA (surrogate of pressure on the distal growth plate)
      was correlated with FL in prepubertal boys (r = -0.249, p = 0.043) and pubertal
      individuals (r = 0.153, p = 0.051). CONCLUSIONS: Results support the hypothesis
      that longitudinal growth precedes modeling at the distal forearm. Confounding
      variables such as puberty may modify the relationship between muscle forces and
      longitudinal growth at the forearm in boys.

PMID- 18824868
TI  - Usefulness of transcription factors Ad4BP/SF-1 and DAX-1 as immunohistologic
      markers for diagnosis of advanced adrenocortical carcinoma.
AB  - BACKGROUND: We examined the expressions of Ad4BP/SF-1 and DAX-1 in primary and
      metastatic lesions of advanced adrenocortical carcinoma with normal hormonal
      findings by immunohistochemistry and discussed their usefulness as
      immunohistochemical markers for diagnosis. PATIENTS AND METHODS: Four patients
      (average age 54.3 +/- 3.9) with retroperitoneal and metastatic tumors were
      enrolled in this study. All patients had normal hormonal findings. Ad4BP/SF-1 and
      DAX-1 underwent immunohistochemical study using needle biopsy specimens from the
      retroperitoneal tumor or metastatic tumor of these patients to diagnose primary
      adrenocortical carcinoma. RESULTS: Immunoreactivity for Ad4BP/SF-1 and DAX-1
      indicated that it was localized exclusively in the nuclei. Ad4BP/SF-1
      immunoreactivity was observed in the carcinoma cells of 2 patients, but not in
      the others, whereas DAX-1 immunoreactivity was observed in the carcinoma cells of
      all 4 patients. CONCLUSION: The expressions of Ad4BP/SF-1 and DAX-1 are
      considered essential to maintain the biological characteristics of adrenocortical
      cells even without abnormal hormonal findings or even after malignant
      transformation and metastasis. These markers are useful to distinguish other
      retroperitoneal tumors, especially in patients with bulky tumors, and to diagnose
      the metastatic site of origin as adrenocortical carcinoma in patients clinically
      presenting with widespread metastasis.

PMID- 18824869
TI  - Impact of patient characteristics and clinical factors on the decision to
      initiate growth hormone treatment in Turner syndrome.
AB  - BACKGROUND/AIMS: To evaluate factors contributing to the decision to initiate
      treatment with growth hormone (GH) in patients with Turner syndrome (TS).
      METHODS: Data collected included ethnicity, parents' education and work status,
      mid-parental height, age at diagnosis, karyotype, pubertal development, clinical
      severity score, bone age, height SDS and ages when GH was proposed and initiated.
      RESULTS: GH was proposed to 59 of 72 patients >6 years (82%), and of these 46
      (78%) accepted. Reasons for not proposing GH included late diagnosis, good growth
      and loss to follow-up. GH-treated and untreated girls differed by age at
      diagnosis (mean +/- SD: 6.8 +/- 4.7 vs. 4.3 +/- 5.1 years; p = 0.04), TS-specific
      height SDS (0.08 +/- 0.81 vs. 066 +/- 0.87; p = 0.01) and spontaneous puberty
      (5/46 vs. 4/26, p = 0.024). Mean age at which it was suggested to begin GH was
      9.2 +/- 2.9 years. Reasons for parental refusal of GH were not related to
      reimbursement issues since GH treatment is covered fully by our insurance plan
      but included concern with other medical issues, mental health problems and fear
      of injections or unknown side effects. CONCLUSION: GH treatment was not
      acceptable to all patients with TS.

PMID- 18824870
TI  - Birth weight and long-term metabolic outcomes: does the definition of smallness
      matter?
AB  - OBJECTIVE: To establish the role of individual definition of smallness at birth
      in the association between birth weight and long-term metabolic outcomes.
      METHODS: Lipid profile and oral glucose tolerance test were performed in young
      adults (22 years) born either small (SGA) or appropriate for gestational age
      (AGA). AGA/SGA were defined by both population-based and customized methods
      adjusting for individual maternal/pregnancy characteristics. 825 individuals were
      classified as AGA and 575 as SGA by both methods, 131 were SGA by the population
      based method only (SGA(pop)) and 22 were SGA by the customized method only
      (SGA(cust)). RESULTS: SGA(cust) subjects had higher total cholesterol and
      triglyceride levels and lower high-density lipoprotein cholesterol concentrations
      than SGA(pop) and AGA subjects, however, insignificantly when adjusted for age,
      gender and body mass index. The homeostasis model assessment for insulin
      resistance (HOMA-IR) index was higher in the SGA(cust) (p = 0.05) and SGA(pop) (p
      = 0.02) versus the AGA group. Controlling for the HOMA-IR index, the
      insulinogenic index was significantly lower in the SGA(cust) versus SGA(pop) (p =
      0.001) and AGA (p = 0.003) groups. In SGA(cust) individuals, the HOMA-IR index
      was clearly shifted to higher, while the insulinogenic index to lower tertiles of
      AGA distribution; SGA(pop) subjects had the HOMA-IR and insulinogenic index
      predominantly in the highest tertiles. CONCLUSIONS: Individualized birth weight
      standards allow to better identify subjects who failed to reach their genetic
      potential of intrauterine growth and are at higher risk of metabolic disturbances
      and impaired insulin secretion later in life.

PMID- 18824871
TI  - Thyroid hypoplasia as a cause of congenital hypothyroidism in Williams syndrome.
AB  - In the Williams-Beuren syndrome (WBS), disorders of the thyroid function and
      morphology have been reported and programs of thyroid screening and surveillance
      are recommended. However, the frequency of biochemical thyroid assessment,
      particularly in the first year of life, is being debated. In this report we
      describe an infant with WBS and congenital hypothyroidism, due to an important
      thyroid hypoplasia. The patient, a 1-month-old female, negative at primary
      neonatal thyroid screening, was referred to our hospital for dyspnea. Thyroid
      function tests showed a raised TSH (42 mIU/l; normal range 0.5-4 mIU/l) with a
      low FT(4) concentration (10.21 pmol/l; normal range: 10.29-24.45 pmol/l).
      Ultrasound examination of the neck showed a significant thyroid hypoplasia,
      whereas (99m)Tc-pertechnetate thyroid scintigraphy evidenced a thyroid gland in
      normal position, with reduced shape and overall weak fixation. Therefore,
      treatment with L-thyroxinewas started. Thyroid hypoplasia is a frequent
      characteristic of WBS and abnormalities of thyroid function are common in
      patients with this feature. Therefore, the possibility of congenital
      hypothyroidism should always be taken into consideration too and, even if
      congenital hypothyroidism neonatal screening is negative, thyroid (morphology and
      function) evaluation should be regularly assessed when the diagnosis is made and,
      thereafter, every year in the first years of life.

PMID- 18824872
TI  - Functional characterization of hepatitis B virus X protein based on the
      inhibition of tumorigenesis in nude mice injected with CCL13-HBx cells.
AB  - OBJECTIVE: This study aimed to determine the effects of HBx on the inhibition of
      tumorigenesis in nude mice injected with CCL13-HBx cells. Therefore, the
      characteristics of the induced tumors and the phenomenon of apoptosis were
      assessed. METHODS: The induced tumors were identified using the specific marker
      of hepatocellular carcinoma (HCC), anti-alpha-fetoprotein (AFP), and their
      characteristics were pathologically examined. Apoptosis was detected by DNA
      fragmentation, and the expression of the proapoptotic proteins p53, Bax, Bad,
      caspase-3, and caspase-8 and the anti-apoptotic protein Bcl-2 was detected by
      Western blotting. To identify possible molecules involved in the inhibition of
      tumorigenesis, extracts of the induced tumors were separated by 2D-PAGE, and the
      proteins were identified by MS. RESULTS: The tumors of the nude mice injected
      with CCL13 and CCL13-HBx cells were identified as HCCs. Moreover, HBx was found
      to suppress tumor growth via apoptosis in the nude mice injected with CCL13-HBx
      cells. The MS findings revealed that phosphorylated myosin light chain was a
      candidate molecule involved in the inhibition of tumorigenesis. CONCLUSION: HBx
      suppressed tumorigenesis in the nude mice injected with CCL13-HBx cells, which
      proved to be a good animal model for the in vivo study of the effects of HBx on
      tumorigenesis.

PMID- 18824873
TI  - Analysis of sequence configurations of the PKR-interacting HCV proteins from
      plasma and PBMC as predictors of response to interferon-alpha and ribavirin
      therapy in HIV-coinfected patients.

PMID- 18824874
TI  - Comparison of Tinzaparin and unfractionated heparin as anticoagulation on
      haemodialysis: equal safety, efficacy and economical parity.
AB  - BACKGROUND: The European Best Practice Guidelines on anticoagulation in chronic
      haemodialysis recommend the use of low-molecular-weight heparins (LMWH) over
      unfractionated heparin (UFH), based on previous small-scale studies and a meta
      analysis which demonstrated equal efficacy of anticoagulation without an increase
      in hemorrhagic events. METHOD: We performed a prospective single-centre study
      where all stable patients on chronic in-hospital haemodialysis were converted
      from UFH to Tinzaparin. Patients were monitored for 2 months before and 2 months
      after the switch. Access failures due to thrombosis, clotted circuits and
      hemorrhagic events were recorded. RESULTS: 1,489 and 1,823 dialysis sessions took
      place on UFH and LMWH, respectively, in 108 patients (65 male). The total number
      of clotted circuits tended to decrease after the switch to LMWH (34 vs. 13) but
      was not statistically significant. There were four minor non-access-related
      episodes of haemorrhage while on treatment with UFH and none with Tinzaparin, and
      the length of bleeding time post needle removal was shorter with Tinzaparin than
      UFH. The cost-analysis demonstrated parity of Tinzaparin with UFH; using a median
      of 10,000 U of UFH versus 2,500 U of LMWH, each therapy cost GBP 10,783 (EUR
      15,942; USD 20,446) per annum. CONCLUSION: Our findings suggest comparable safety
      and efficacy of Tinzaparin, parity of cost in comparison with UFH.

PMID- 18824875
TI  - Nitric oxide involvement in TNF-alpha and IL-1 beta-mediated changes in human
      mesangial cell MMP-9 and TIMP-1.
AB  - BACKGROUND: Mesangial cells are known to secrete metalloproteinases (MMPs) and
      tissue inhibitors of metalloproteinases (TIMPs) that are capable of disrupting
      the glomerular basement membrane (GBM). Disruption of the GBM appears to be an
      important mechanism in the renal disease process, however little is known about
      the mechanisms involved. Therefore we examined the potential role of nitric oxide
      (NO) in the regulation of MMP-9 and TIMP-1 by tumour necrosis factor-alpha (TNF
      alpha) and interleukin-1 beta (IL-1 beta) using the human mesangial cell line
      (HMCL). METHODS: The HMCL was treated with various concentrations of cytokines
      and NO inhibitors. Activity of MMP-9 was examined by gelatin zymography and TIMP
      1 expression was analysed by Western blotting. NO production was measured using
      the Greiss assay. RESULTS: In this study, stimulation of HMCL cells with TNF
      alpha or IL-1 beta, alone or in combination, led to a substantial increase in NO
      production, which was shown to result from an increase in the expression of the
      inducible form of NOS (iNOS). Treatment of cells with the specific iNOS inhibitor
      L-NIL potentiated the increase in MMP-9 production induced by TNF-alpha, but
      prevented the suppression of TIMP-1 production observed following cytokine
      treatment. The NO donor, sodium nitroprusside, also stimulated a substantial
      increase in NO production in HMCL cells, which was associated with a reduction in
      basal and TNF-alpha-stimulated MMP-9 and a potentiation of the cytokine-induced
      decrease in TIMP-1. CONCLUSIONS: Our study provides convincing evidence of a
      modulatory role for NO on cytokine-induced MMP-9 and TIMP-1 production in human
      mesangial cells.

PMID- 18824877
TI  - Promoter hypermethylation in tumour suppressor genes shows association with
      stage, grade and invasiveness of bladder cancer.
AB  - AIMS: Superficial bladder cancer is a highly recurrent disease, with progression
      to muscle invasiveness occurring in 15-30% of cases. Promoter hypermethylation in
      a panel of tumour suppressor genes involved in cell cycle control, apoptosis and
      DNA repair was analyzed in superficial bladder tumours in order to evaluate the
      suitability of epigenetic biomarkers for an earlier prediction of the aggressive
      course of the disease. METHOD: Promoter hypermethylation in p16, RARbeta,
      RASSF1A, DAPK, and MGMT genes was analyzed in 58 cases with superficial bladder
      cancer and 2 cases with benign urological disease using methylation-specific PCR.
      RESULTS: Promoter hypermethylation was frequently detected in RARbeta, RASSF1A
      and DAPK genes, and 62% of bladder tumours exhibited hypermethylation in at least
      one gene. The overall frequency of hypermethylation and the number of genes
      involved increased with tumour stage, grade and muscle invasiveness. Aberrant
      methylation of RASSF1A and RARbetawas predominant (p < 0.05) in muscle-invasive
      tumours and high-grade tumours, respectively. Cases with concurrent
      hypermethylation in DAPK, p16 and RARbeta genes were moresusceptible to relapse.
      CONCLUSION: The results suggest analysis of promoter hypermethylation as a
      valuable biomarker for prognosis of the aggressive course of disease in bladder
      cancer.

PMID- 18824876
TI  - Efficient inhibition of ovarian cancer growth and prolonged survival by
      transfection with a novel pro-apoptotic gene, hPNAS-4, in a mouse model. In vivo
      and in vitro results.
AB  - OBJECTIVE: We transfected ovarian cancer cells and administered recombinant
      plasmid encoding hPNAS-4 to nude mice bearing ovarian cancer, aiming to evaluate
      the effect of hPNAS-4 against ovarian cancer in vitro and in vivo. METHODS:
      Ovarian cancer SKOV3 cells were transfected with hPNAS-4-plasmid, and cell
      proliferation was evaluated by MTT assay; apoptosis was examined by DNA ladder,
      Hoechst33258 staining and flow-cytometric assays. Nude mice bearing ovarian
      cancers were treated with hPNAS-4-p/liposome. Tumor growth was determined and
      survival was recorded. TUNEL assay and microvessel density was assessed to
      evaluate apoptosis and angiogenesis. RESULTS: Both inhibition of proliferation (p
      < 0.05) and induction of apoptosis (p < 0.05) were observed in SKOV3 cells
      transfected with hPNAS-4-p in vitro. In hPNAS-4-p-treated tumor cells in vivo,
      tumor growth significantly decreased, while the survival time of tumor-bearing
      mice was prolonged compared with control groups (p < 0.05). Increased apoptosis
      of tumor cells and decreased angiogenesis in tumor tissue were also observed.
      CONCLUSIONS: Our promising results on the potential antitumor effects of hPNAS-4
      on ovarian cancer in vitro and in vivo may be explained, in part, by the
      induction of apoptosis and inhibition of angiogenesis. Consequently, hPNAS-4 has
      potential as a new gene therapy for human ovarian cancer.

PMID- 18824878
TI  - 'As a mentor, your expectation should be that your mentees in their career will
      accomplish more than you have'. An interview with Peter A. Banks, MD, Director,
      Center for Pancreatic Disease, Brigham and Women's Hospital, Boston, Mass., USA.
      Interview by Martin E. Fernandez-Zapico.
AB  - Dr. Peter Banks has made an outstanding contribution to the understanding of
      pancreatic diseases. His exceptional achievements in the field of pancreatitis
      were seminal for the characterization of the pathogenesis of pancreatic diseases
      as well as its diagnosis and therapy. In this interview, Dr. Banks shares with
      Pancreatology his experience as a pancreatic researcher.

PMID- 18824879
TI  - Animal models in pancreatic surgery: a plea for pork.
AB  - There has been resurgence in the utilization of larger animal models in medicine
      over the last decade, particularly in the field of pancreatic research. With
      increasing pressures to more accurately replicate the human model prior to
      clinical application, an ideal animal model is necessary. Previous work in larger
      species (dog, pig) in pancreatic surgery research has identified several key
      anatomical differences that have led us to conclude that perhaps the swine is a
      model better fit for more accurate human representation.

PMID- 18824880
TI  - Caffeic acid phenethyl ester induces apoptosis of human pancreatic cancer cells
      involving caspase and mitochondrial dysfunction.
AB  - AIMS: This study aimed to investigate the effect of caffeic acid phenethyl ester
      (CAPE), an active component isolated from honeybee propolis, in inducing
      apoptosis in human pancreatic cancer cells. METHODS: Inhibition of viability of
      BxPC-3 and PANC-1 cell lines induced by CAPE was estimated by a trypan blue dye
      exclusion test. The type of cell death in BxPC-3 after CAPE treatment was
      characterized by observation of morphology, sub-G1 DNA content, annexin-V/PI
      staining, caspase-3 and caspase-7 assay, and DNA agarose gel electrophoresis.
      RESULTS: CAPE (10 microg/ml) resulted in marked inhibition of viability of BxPC-3
      (80.4 +/- 4.1%) and PANC-1 (74.3 +/- 2.9%) cells. CAPE induced a time-dependent
      increase in hypodiploid percentage and a significant decrease in mitochondrial
      transmembrane potential in BxPC-3 cells. It induced morphological changes of
      typical apoptosis, but no DNA fragmentation was noted by DNA electrophoresis. The
      inhibition of growth and increased in the proportion of sub-G(1) cells was
      partially blocked by pretreatment with the pan-caspase inhibitor Z-VAD-fmk (50
      microM) in BxPC-3 cells indicating a caspase-related mechanism in CAPE-induced
      apoptosis. Caspase-3/caspase-7 activity was approximately 2 times greater in CAPE
      treated BxPC-3 cells compared with control cells. CONCLUSIONS: These results
      suggest that CAPE is a potent apoptosis-inducing agent. Its action is accompanied
      by mitochondrial dysfunction and activation of caspase-3/caspase-7.

PMID- 18824881
TI  - Synchronous and metachronous extrapancreatic malignant neoplasms in patients with
      intraductal papillary-mucinous neoplasm of the pancreas.
AB  - BACKGROUND/AIMS: Patients with intraductal papillary-mucinous neoplasm (IPMN) of
      the pancreas are likely to have a better prognosis than those with conventional
      pancreatic ductal adenocarcinoma. Recently there have been some reports on
      extrapancreatic malignant neoplasms (EPM) occurring in patients with IPMN. The
      purpose of this study was to discover the characteristic features of IPMN with
      EPM compared with IPMN without EPM. METHODS: 61 patients with IPMN who underwent
      surgery at Tohoku University Hospital between 1988 and 2006 were retrospectively
      analyzed. RESULTS: The 61 patients with IPMN in this study comprised 25 with
      intraductal papillary-mucinous adenomas (IPMA) and 36 with intraductal papillary
      mucinous carcinomas (IPMC) including 6 with invasive carcinomas. Synchronous and
      metachronous EPM were observed in 15 out of the 61 patients (24.6%). Three of
      these patients, including 2 with IPMA and 1 with invasive carcinoma associated
      with IPMC, died of the EPM. None of the features, including sex, age, smoking,
      family history, macroscopic types (main duct type or branch duct type),
      histological types (gastric, intestinal, pancreatobiliary or oncocytic), and
      aberrant expression of molecules including CDKN2A, TP53, SMAD4 and DUSP6, except
      for the histological diagnoses were associated with the occurrence of EPM, i.e.,
      the EPM occurred more often in patients with IPMA (10 out of 25) than in those
      with IPMC (5 out of 36) in our series (p = 0.0199 by the chi(2) test, p = 0.0330
      by Fisher's exact probability test, p = 0.0422 by Yates' correction). CONCLUSION:
      Patients with IPMA were more likely to have EPM than those with IPMC. Patients
      with IPMA are usually expected to have a fair prognosis but EPM could be fatal in
      some of them, so it must be noted during follow-up.

PMID- 18824882
TI  - Occurrence of metabolic osteopathy in patients with chronic pancreatitis.
AB  - INTRODUCTION: Chronic pancreatitis is an inflammatory disease manifested by
      maldigestion and, in an advanced stage, by malabsorption. The aim of our research
      was to monitor the occurrence of metabolic osteopathies (osteopenia, osteoporosis
      and osteomalacia) in patients with chronic pancreatitis. PATIENTS AND METHODS:
      The group consisted of 73 patients (17 women and 56 men) in different stages of
      chronic pancreatitis. In all patients we determined serum concentrations of Ca,
      P, 25-OH vitamin D, 1,25-(OH)(2) vitamin D, alkaline phosphatase and its bone
      isoenzyme. Bone mineral density was measured by dual-energy X-ray absorptiometry
      (DXA) in the lumbar spine (L(1)-L(4)) and in the proximal femur. When bone
      pathology was identified by DXA, we determined the other to exclude other causes
      of secondary osteopathy and the 24-hour loss of calcium and phosphorus in the
      urine. RESULTS: Osteopathy was found in 39% of patients, i.e. osteopenia in 26%,
      osteoporosis in 5% and osteomalacia in 8% of cases. CONCLUSION: The occurrence of
      relatively high percentages of metabolic osteopathies in patients with chronic
      pancreatitis may correlate, namely in advanced stages of the disease, with the
      malabsorption of vitamin D to the enterohepatic circulation. In initial forms of
      pancreatitis, it is not possible to exclude progression of osteopathy due to
      changes of the intestinal flora, with disturbance of vitamin D absorption to the
      intestinal mucosa.

PMID- 18824883
TI  - Pleural effusions in critically ill patients.
AB  - Pleural effusions (PEs) are common in critically ill patients mainly as a
      consequence of severe cardiopulmonary disorders frequently encountered in these
      patients. Their impact on the pathophysiology of acute respiratory failure
      remains unknown. They are usually small and uncomplicated transudates that are
      easily overlooked on a supine portable chest X-ray and do not require drainage or
      infectious exudates that always require thoracocentesis. The diagnosis of PEs in
      critically ill patients has been revolutionized with the advent of chest
      ultrasound allowing easy bedside quantification of pleural fluid and making
      thoracocentesis a safe procedure especially in high-risk patients on mechanical
      ventilation. CT provides a much more accurate evaluation of the size and location
      of PEs and is extremely helpful in the guidance of catheters into loculated fluid
      collections. Hemothorax in critically ill patients is usually related to trauma
      or surgical interventions and requires early drainage and possibly surgical
      exploration.

PMID- 18824884
TI  - Is it possible to reduce the use of antibiotics in severe exacerbations of
      chronic obstructive pulmonary disease?

PMID- 18824885
TI  - Single gene expression as a prognostic marker in idiopathic interstitial
      pneumonia?

PMID- 18824886
TI  - Bronchoscopic microsampling to analyze the epithelial lining fluid of patients
      with pulmonary Mycobacterium avium complex disease.
AB  - BACKGROUND: A new bronchoscopic microsampling (BMS) probe has recently been
      developed, which allows the minimally invasivecollection of epithelial lining
      fluid (ELF) simultaneously from multiple sites. While the number of
      immunocompetent patients with pulmonary Mycobacterium avium complex(MAC) disease
      is growing, the precise pathogenesis of the disease remains to be clarified.
      OBJECTIVES: This study aimed to measure biochemical markers in the ELF of
      patients with pulmonary MAC disease using BMS. METHODS: We studied 8 healthy
      volunteers (controls) and 8 patients with pulmonary MAC disease. In the patients,
      ELF was collected from visibly abnormal (involved) and normal (uninvolved) sites
      using high-resolution computed tomography (HRCT). RESULTS: The concentration of
      IFN-gamma (means +/- SEM) was significantly higher in patient ELF sampled from
      involved (26.62 +/- 9.66 pg/ml) than from uninvolved sites (5.33 +/- 1.44 pg/ml;
      p < 0.05) or from normal controls (<1.56 pg/ml; p < 0.05). In most patients,
      there was no difference in IFN-gamma concentrations between the involved and
      uninvolved sites. The concentration of KL-6 in ELF was significantly higher in
      the involved (793 +/- 108 U/ml) than in the uninvolved sites (192 +/- 43 U/ml;p <
      0.05) or in normal controls (186 +/- 38 U/ml;p < 0.05). CONCLUSIONS: The specific
      inflammatory reaction caused by MAC infection might not be limited to sites that
      were visibly abnormal on HRCT. Although further improvement has to be considered,
      BMS may help to increase the understanding of the pathogenesis of various
      respiratory disorders.

PMID- 18824887
TI  - Marker development for erect versus pendant-orientated fruit in Capsicum annuum
      L.
AB  - The erect habit of fruit setting is a unique characteristic of ornamental peppers
      and wild pepper species. The erect habit is known to be controlled by the up
      locus on pepper (Capsicum annuum L.) chromosome 12. The result of a genetic
      analysis using Saengryeog 211 (pendant), Saengryeog 213 (erect), and their F1 and
      BC1 progeny demonstrated that up is a recessive gene. To develop an up-linked
      marker, bulked segregant analysis (BSA) and amplified fragment length
      polymorphism (AFLP) were employed using 108 F2:3 individuals. The closest AFLP
      marker, A2C79, was located at a genetic distance of 1.7 cM from the up locus and
      was converted into a cleaved amplified polymorphic sequence (CAPS) marker. This
      marker was mapped at a genetic distance of 4.3 cM from the up locus. When the
      CAPS was applied to seven ornamental lines and 27 breeding lines with erect
      fruit, these genotypes of 28 lines were correctly predicted. Thus, the CAPS
      marker will be useful for marker-assisted selection (MAS) of pepper breeding
      lines with the up allele at the early seedling stage.

PMID- 18824888
TI  - Barriers to providing dual energy x-ray absorptiometry services to individuals
      with spinal cord injury.
AB  - To assess barriers to bone mineral density testing in individuals with chronic
      spinal cord injury, a cross-sectional study of 20 individuals with spinal cord
      injury was conducted with assessment of physical and logistical barriers to dual
      energy x-ray absorptiometry scanning. We identified several barriers, including
      scanner design and configuration in the scanning room that limited accessibility,
      increased typical scanning time, and made additional staff necessary. For dual
      energy x-ray absorptiometry to become a routine component of ongoing care in
      spinal cord injury medicine, we recommend the following changes: (1) install
      ceiling-mounted hydraulic lifts and grab bars to facilitate transfers in the
      scanning room; (2) increase staffing during scans; (3) increase time allotment
      for scans; (4) install the scanner in an adequately-sized room; and (5) partner
      with administrators and staff to raise awareness of access issues faced by
      individuals with spinal cord injury.

PMID- 18824889
TI  - Influence of varying level terrain on wheelchair propulsion biomechanics.
AB  - OBJECTIVE: To evaluate manual wheelchair propulsion across level ground
      conditions that are encountered during everyday life. DESIGN: Subjects included
      14 individuals (13 with spinal cord injury [SCI], 1 with spina bifida) who were
      experienced manual wheelchair users and had no current upper extremity injury or
      pain complaints. Subjects propelled their wheelchairs at a self-selected speed
      across four different level ground conditions, including smooth and aggregate
      concrete and tile and carpet flooring. Temporal and kinetic measurements were
      obtained bilaterally from instrumented wheelchair rims during the steady-state
      phase of propulsion. RESULTS: There were no side-to-side differences for any of
      the temporal or kinetic variables. Propulsion velocity and pushrim contact time
      were consistent across ground conditions. Propulsion frequency was significantly
      greater during both concrete conditions than either tile or carpet ground
      conditions. Forces and moments were greatest during the aggregate concrete ground
      condition and lowest during propulsion across tile flooring. CONCLUSIONS: The
      rolling resistance of level surface terrain significantly impacts wheelchair
      propulsion biomechanics. Identification of environmental conditions that may
      contribute to upper extremity pathology is a step toward injury prevention and
      maintenance of functional abilities for the manual wheelchair user. These results
      may be used to assist with home and community terrain design to minimize the
      demands associated with wheelchair propulsion.

PMID- 18824891
TI  - Re: Duplication of the muscularis mucosae in Barrett esophagus: an
      underrecognized feature and its implication for staging of adenocarcinoma.

PMID- 18824892
TI  - Mucus rupture (extrusion) and duct expansion/expansive growth are not diagnostic
      of minimal invasion when seen with intraductal papillary mucinous neoplasms.

PMID- 18824894
TI  - Comment on "Cardiac Behcet disease presenting as aortic valvulitis/aortitis or
      right heart inflammatory mass: a clinicopathologic study of 12 cases".

PMID- 18824895
TI  - Plexiform angiomyxoid tumor of the stomach.

PMID- 18824897
TI  - Re: Plexiform angiomyxoid myofibroblastic tumor of the stomach.

PMID- 18824898
TI  - Pretreatment with the Gram-positive bacterial cell wall molecule peptidoglycan
      improves bacterial clearance and decreases inflammation and mortality in mice
      challenged with Staphylococcus aureus.
AB  - OBJECTIVE: To determine whether tolerance and enhancement of innate immune
      function can be induced by the Gram-positive cell wall component peptidoglycan.
      DESIGN: Controlled, in vivo laboratory study. SUBJECTS: Male mice, 8-12 wks
      (C57BL6/J; C3H/HeJ; B6.129-Tlr2/J). INTERVENTIONS: Mice were given
      intraperitoneal injections of 1 mg peptidoglycan on two consecutive days. Mice
      were then challenged with an intravenous injection of live Staphylococcus aureus
      (1 x 10 colony-forming units) 2 days after the second pretreatment. MEASUREMENTS
      AND MAIN RESULTS: Mice pretreated with peptidoglycan had diminished plasma
      concentrations of tumor necrosis factor-alpha and interferon-gamma in response to
      the bacterial challenge when compared with untreated controls. Plasma interleukin
      10 after bacterial challenge was higher in peptidoglycan-pretreated mice than in
      controls. Clearance of bacteria after the staphylococcal challenge was improved
      in mice pretreated with peptidoglycan, and mortality in response to a subsequent
      Staphylococcus challenge was significantly attenuated. Peptidoglycan pretreatment
      of mice lacking intact toll-like receptor-4 signaling (C3H/HeJ) or toll-like
      receptor-2 signaling (toll-like receptor-2 knockouts) had similar effects on
      plasma cytokine balance, bacterial clearance, and mortality. CONCLUSIONS:
      Exposure to peptidoglycan significantly attenuated inflammation and enhanced
      bacterial clearance after a subsequent challenge with S. aureus. These results
      show that exposure to Gram-positive bacterial cell wall components can induce
      tolerance and enhance innate immune function and neither toll-like receptor-2 nor
      toll-like receptor-4 are necessary for this phenomenon. Further, although the
      altered cytokine balance is similar to that seen in septic patients, induced
      tolerance differs importantly from the clinical scenario of sepsis in that
      bacterial clearance and survival are improved compared with normal control
      animals.

PMID- 18824899
TI  - Acute lung injury following blood transfusion: expanding the definition.
AB  - OBJECTIVE: Acute lung injury (ALI) is a well known complication following the
      transfusion of blood products and is commonly referred to as transfusion-related
      acute lung injury (TRALI). The objectives of this review are to summarize current
      knowledge of TRALI with an emphasis on issues pertinent to the intensivist and to
      define the newly recognized "Delayed TRALI syndrome." DATA SYNTHESIS: The classic
      TRALI syndrome is an uncommon condition characterized by the abrupt onset of
      respiratory failure within hours of the transfusion of a blood product. It is
      usually caused by anti-leukocyte antibodies, resolves rapidly, and has a low
      mortality. A single unit of packed cells or blood component product is usually
      implicated in initiating this syndrome. It has, however, recently been recognized
      that the transfusion of blood products in critically ill or injured patients
      increases the risk (odds ratio 2.13; 95% confidence interval 1.75-2.52) for the
      development of the ALI 6-72 hours after the transfusion. This "delayed TRALI
      syndrome" is common, occurring in up to 25% of critically ill patients receiving
      a blood transfusion, and is associated with a mortality of up to 40%. While the
      delayed TRALI syndrome can develop after the transfusion of a single unit, the
      risk increases as the number of transfused blood products increase. The
      management of both the classic and delayed TRALI syndromes is essentially
      supportive. CONCLUSIONS: Both the classic and delayed TRALI syndromes are among
      the most important complications following the transfusion of blood products and
      are associated with significant morbidity and increased mortality. The risk and
      benefits of all blood products should be assessed before transfusion.

PMID- 18824900
TI  - Regionalization of medical critical care: what can we learn from the trauma
      experience?
AB  - OBJECTIVE: To review the rationale for the regionalization of adult critical care
      and discuss how lessons from the trauma experience may be relevant to this
      debate. DESIGN: Narrative review and opinion. RESULTS: Variation in the quality
      of critical care among hospitals has prompted calls for regionalization of care
      for critically ill patients. Because of similarities between trauma and critical
      care, trauma is often cited as a model for the regionalization of critical care
      services. In reality, there are both important similarities and differences
      between trauma and critical care. In addition, many lessons from the trauma
      experience directly apply to future efforts to regionalize critical care
      services. In this article, we review the analogy between the regionalization of
      trauma and critical care and discuss how the trauma experience both supports and
      limits the argument for creation of a formal regionalized system of care for the
      critically ill. If regionalization efforts in critical care are to proceed, the
      lessons of the trauma experience can inform policy decisions and provide insight
      into the design and implementation of an effective regionalized system.

PMID- 18824901
TI  - The pulmonary artery catheter: in medio virtus.
AB  - OBJECTIVE: To clarify the role of the pulmonary artery catheter in the intensive
      care unit. DATA SOURCES: Recent and relevant literature from MEDLINE and authors'
      personal databases. STUDY SELECTION: Studies on pulmonary artery catheter use and
      use of other monitoring devices in critically ill patients. DATA EXTRACTION:
      Based largely on clinical experience and assessment of the relevant published
      literature and in response to recent articles attacking the pulmonary artery
      catheter, we propose that the pulmonary artery catheter is still a valuable tool
      for the hemodynamic monitoring of patients with complex disease processes in whom
      the information obtained from the pulmonary artery catheter may influence
      management. We suggest that there is a need to revisit the basics of hemodynamic
      management and reassess the way in which the pulmonary artery catheter is used,
      applying three key principles: correct measurement, correct data interpretation,
      and correct application. CONCLUSION: The pulmonary artery catheter is still a
      valuable tool for hemodynamic monitoring when used in selected patients and by
      physicians adequately trained to correctly interpret and apply the data provided.

PMID- 18824902
TI  - Cerebral blood flow thresholds for cerebral ischemia in traumatic brain injury. A
      systematic review.
AB  - BACKGROUND: Reduction of cerebral blood flow plays a crucial role in causing
      posttraumatic cerebral ischemia. However, the methodologic adequacy of studies
      from which currently used cerebral blood flow thresholds in traumatic brain
      injury have been derived has not been evaluated. OBJECTIVE: To systematically
      evaluate the evidence available on cerebral blood flow thresholds and its
      methodologic adequacy in adults with traumatic brain injury. METHODS: Included
      were primary studies on adults with traumatic brain injury in which cerebral
      blood flow thresholds were evaluated and reported, and follow-up brain computed
      tomography or magnetic resonance imaging was used as the gold standard for
      diagnosing the finally infarcted area. RESULTS: Among the 53 diagnostic studies
      identified, 31 did not report any threshold value, whereas 20 studies used
      thresholds derived from the literature, mainly animal or clinical studies on
      ischemic stroke. One study measured cerebral blood flow thresholds, but did not
      use accepted neuroradiological criteria for the diagnosis of posttraumatic
      cerebral ischemia. The remaining study fulfilled all methodologic inclusion
      criteria, but was restricted to 14 patients with severe traumatic brain injury
      and cerebral contusion. This study proposed a cerebral blood flow threshold of 15
      mL/100 mL/min, with sensitivity and specificity of 43% and 95%, respectively.
      CONCLUSIONS: Cerebral blood flow thresholds for the diagnosis of posttraumatic
      cerebral ischemia are based on weak evidence, and cannot be recommended.

PMID- 18824903
TI  - B-type natriuretic peptide as a marker for sepsis-induced myocardial depression
      in intensive care patients.
AB  - INTRODUCTION: In early stages of septic shock, impaired myocardial function plays
      an important prognostic role. In this context, B-type natriuretic peptide (BNP)
      has been shown to be a neurohumoral marker for left ventricular dysfunction,
      because myocardial strain and ischemia both increase BNP concentration. The
      present study was designed to test if BNP allows for identification of patients
      at risk for developing sepsis-induced myocardial depression and if an increased
      concentration of BNP is associated with an adverse outcome in patients with
      septic shock. METHODS AND RESULTS: In a prospective study, 93 patients with
      septic shock were divided into one group with normal ventricular function (left
      ventricular ejection fraction >50%) on days 3 to 5 (n = 38) and another group of
      patients with impaired left ventricular function (left ventricular ejection
      fraction <50%) on days 3 to 5 (n = 55). Patients with impaired left ventricular
      function had an increased median plasma BNP concentration on day 5 (699 [608 of
      795.5] pg/nL vs. 86 [71.3 of 93] pg/nL) and an ejection fraction of 38 +/- 6% on
      day 5 vs. 58 +/- 7% in patients without impaired left ventricular function. There
      was a close inverse relation between increased plasma BNP concentrations and
      depressed left ventricular ejection fraction (p < 0.05). BNP measured at days 3
      and 5 revealed an association with the end point of survival. In the proportional
      hazards regression model adjusted for age, male gender, and creatinine
      concentration, measured at days 0, 3, 5, and 12, BNP concentration at day 5
      showed an increased hazard for reaching the end point (hazard ratio: 1.407; 95%
      confidence interval: 1.033-1.916; p = 0.030). In an additional receiver operating
      characteristic curve analysis, the predictive value of a model including
      cardiovascular risk factors and additional BNP concentration on day 5, compared
      with a baseline model of cardiovascular risk factors, improved the area under the
      curve the most; therefore, this model was suited best for prediction of sepsis
      induced myocardial depression and 30-day survival for patients with septic shock.
      Area under the curve of this model combined with BNP concentration at day 5 for
      death after 30 days (0.65) impaired left ventricular ejection fraction (0.94) and
      sepsis-induced myocardial depression (0.96). CONCLUSION: These results indicate
      that plasma BNP concentration represents a reliable marker for identification of
      patients developing sepsis-induced myocardial depression. In addition, BNP
      concentration on day 5 may be used as a prognostic marker to identify patients
      with an elevated risk for an adverse outcome.

PMID- 18824904
TI  - The use of regional citrate anticoagulation for continuous venovenous
      hemodiafiltration in acute kidney injury.
AB  - OBJECTIVE: Continuous renal replacement therapy is commonly used in the treatment
      of acute kidney injury. Although the optimal anticoagulation system is not well
      defined, citrate has emerged as the most promising method. We evaluated the data
      of 143 patients with acute kidney injury subjected to citrate-based continuous
      venovenous hemodiafiltration. DESIGN: Retrospective cohort study. SETTING:
      Intensive care unit of tertiary care private hospital. PATIENTS: Patients with
      acute kidney injury treated from February 2004 to July 2006. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: The main cause of acute kidney injury was sepsis
      (58%). The mean dialysis dose was 36.6 mL/kg/hr allowing for excellent metabolic
      control (last tests: creatinine, 1.1 mg/dL; urea, 46 mg/dL). No significant
      bleeding, severe electrolyte, or calcium disorders were observed. Of the 418
      filters used, almost 28,000 hrs of treatment, hemofilter patency was 68% at 72
      hrs. Hospital mortality was 59%, and 22% of survivors were dialysis-dependent at
      the time of discharge. Within our sample, we identified 21 patients with liver
      failure (mean prothrombin time index, 21% vs. 67%, p < 0.001). This group
      presented with a lesser median systemic ionized calcium level (1.06 vs. 1.12
      mmol/L, p < 0.001) and similar mean total calcium level (8.5 vs. 8.6 mg/dL, not
      significant), compared with patients without liver failure. These subjects also
      showed acidemia (median pH, 7.31 vs. 7.40, p < 0.001); however, they exhibited
      higher levels of lactate (median 29 vs. 16 mg/dL, p < 0.001), chloride (mean 109
      vs. 107 mEq/L, p = 0.045) and had a trend to higher mortality rate (76% vs. 56%).
      CONCLUSIONS: Besides a trend toward higher mortality rate observed in the group
      with liver failure, we found that citrate-based continuous venovenous
      hemodiafiltration allowed an effective dialysis dose and reasonable filter
      patency.

PMID- 18824905
TI  - Effects of elevating the head of bed on interface pressure in volunteers.
AB  - OBJECTIVE: Intensive care unit patients are at particular risk for pressure
      ulcers and ventilator-associated pneumonia. Current guidelines recommend that
      mechanically ventilated patients be kept in a semirecumbent position with the
      head of bed elevated 30 degrees -45 degrees to prevent aspiration and ventilator
      associated pneumonia. We tested the effects of elevating the head of bed on the
      interface pressure between the skin of the sacral area and the bed with healthy
      volunteers. INTERVENTIONS: Interface pressure profiles of the sacral area were
      obtained for the 0 degrees , 10 degrees , 20 degrees , 30 degrees , 45 degrees ,
      60 degrees , and 75 degrees head of bed elevated positions from 15 subjects (14
      men, one woman). MEASUREMENTS AND MAIN RESULTS: Peak sacral interface pressures
      increased with large increases in head of bed elevation. The 30 degrees , 45
      degrees , 60 degrees , and 75 degrees head of bed positions all had peak
      interface pressures that were significantly (p < 0.02) greater than the supine
      measurement and also were different from all other head of bed positions.
      Affected areas, defined as areas over which an interface pressure >or=32 mm Hg
      was obtained, increased with large elevation of the head of bed. The affected
      areas of the 45 degrees , 60 degrees , and 75 degrees head of bed positions were
      significantly greater than the supine position and were also significantly
      different from all other head of bed positions. CONCLUSIONS: Raising the head of
      bed to 30 degrees or higher on a intensive care unit bed increases the peak
      interface pressure between the skin at the sacral area and support surface in
      healthy volunteers. At 45 degrees head of bed elevation or higher, the affected
      area attributed to a skin-intensive care unit bed interface pressure >or=32 mm Hg
      increased as well. Further study is needed to determine whether the increased
      peak interface pressures and affected areas that result from raising the head of
      bed actually increase the incidence of pressure ulcer formation.

PMID- 18824906
TI  - Early intravenous unfractionated heparin and mortality in septic shock.
AB  - BACKGROUND: Sepsis and septic shock represent a systemic inflammatory state with
      substantial pro-coagulant elements. Unfractionated heparin is a known
      anticoagulant, which also possesses anti-inflammatory properties. Unfractionated
      heparin has been shown to increase survival in experimental models of septic
      shock. OBJECTIVE: To evaluate the impact of intravenous therapeutic dose
      unfractionated heparin in a cohort of patients diagnosed with septic shock.
      DESIGN: Retrospective, propensity matched, multicenter, cohort study. SETTING:
      Regional intensive care units in Winnipeg, Canada between 1989 and 2005.
      PATIENTS: Two thousand three hundred fifty-six patients diagnosed with septic
      shock, of which 722 received intravenous therapeutic dose heparin. MEASUREMENTS
      AND MAIN RESULTS: The primary outcome of study was 28-day mortality, and
      mortality stratified by severity of illness (Acute Physiologic and Chronic Health
      Evaluation II quartile). Safety was assessed by comparing rates of
      gastrointestinal hemorrhage, intracranial hemorrhage, and the need for
      transfusion. By using a Cox proportional hazards model, systemic heparin therapy
      was associated with decreased 28-day mortality (307 of 695 [44.2%] vs. 279 of 695
      [40.1%]; hazard ratio 0.85 [confidence interval (CI) 95% 0.73-1.00]; p = 0.05).
      In the highest quartile of severity of illness (Acute Physiologic and Chronic
      Health Evaluation II score 29-53), heparin administration was associated with a
      clinically and statistically significant reduction in 28-day mortality [127 of
      184 (69.0%) vs. 94 of 168 (56.0%); hazard ratio 0.70 (CI 95% 0.54-0.92); p =
      0.01]. The use of intravenous unfractionated heparin was associated with
      successful liberation from mechanical ventilation [odds ratio of 1.42 (CI 95%
      1.13-1.80); p = 0.003], and successful discontinuation of vasopressor/inotropic
      support [odds ratio of 1.34 (CI 95% 1.06-1.71); p = 0.01]. No significant
      differences in the rates of major hemorrhage or need for transfusion were
      identified. CONCLUSION: Early administration of intravenous therapeutic dose
      unfractionated heparin may be associated with decreased mortality when
      administered to patients diagnosed with septic shock, especially in patients with
      higher severity of illness. Prospective randomized trials are needed to further
      define the role of this agent in sepsis and septic shock.

PMID- 18824907
TI  - Effect of laboratory testing guidelines on the utilization of tests and order
      entries in a surgical intensive care unit.
AB  - OBJECTIVE: Diagnostic testing is frequently overused in the intensive care unit.
      We devised guidelines to optimize blood tests utilization, and designed this
      study to quantify their efficacy over time, their safety, and their possible
      benefits. DESIGN: Laboratory testing guidelines were created by consensus and
      implemented through repeated staff education. The guidelines included: a) the
      tests to be obtained daily: complete blood count, serum electrolytes, urea
      nitrogen, creatinine, and blood glucose concentration; b) the need to discuss
      laboratory testing at daily patient's rounds; c) the need to provide a written
      order for all tests. The number of tests performed, corresponding physician
      orders, and various outcome measures were collected for two 6-month study
      periods, before and after the first day of implementation of the guidelines.
      SETTING: Twenty-bed surgical intensive care unit in a tertiary care teaching
      hospital. PATIENTS: All patients admitted during the two study periods. METHODS:
      Laboratory tests and related physician orders, demographics, blood products
      transfusion, and outcomes were collected from hospital databases. In
      prospectively defined subgroups, additional outcome measures were obtained by ad
      hoc chart review. RESULTS: One thousand one hundred seventeen patients were
      enrolled. After the institution of the guidelines, the number of laboratory tests
      decreased by 37% (from 64,305 to 40,877), and the number of respective physician
      orders increased by 38% (from 20,940 to 35,472), p < 0.001. These results were
      manifest within 1 month, sustained through the study period, and still present at
      1 yr. No changes in outcomes or in the rates of selected complications were
      detected. Red blood cells utilization correlated linearly (r .47) with the number
      of blood tests performed in both study periods. CONCLUSIONS: Guidelines designed
      to optimize laboratory tests use in an intensive care unit can produce rapid and
      long-lasting effects, can be safe, and may affect the number of red blood cell
      units transfused.

PMID- 18824908
TI  - Glycemic variability: a strong independent predictor of mortality in critically
      ill patients.
AB  - OBJECTIVES: To determine the effect of glycemic variability, assessed by the
      standard deviation of each patient's mean glucose level, on mortality in a
      population of critically ill adult patients. DESIGN: Retrospective review of a
      large cohort of prospectively evaluated patients. SETTING: Fourteen-bed medical
      surgical adult intensive care unit of a university affiliated community hospital.
      PATIENTS: Three thousand two hundred fifty-two patients consecutively admitted
      between October 1999 and October 2007 with at least three venous glucose samples.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The mean (sd) Acute
      Physiology and Chronic Health Evaluation II score of the 3252 patients was 20.0
      (8.9) and their mortality was 24.4%, ranging from 18.1% among patients with mean
      glucose level 70 mg/dL to 99 mg/dL to 35.9% among patients with mean glucose
      level 180+ mg/dL. The relationship between glycemic variability and mortality was
      strongest in the euglycemic range. For the 410 patients with mean glucose level
      70 mg/dL to 99 mg/dL, mortality ranged from 5.9% in the first quartile of
      glycemic variability to 30.1% in the fourth; for the 1031 patients with mean
      glucose level 100 mg/dL to 119 mg/dL the corresponding range was 9.7% to 31.0%.
      Mortality among patients in the entire cohort with the lowest quartile of
      glycemic variability was 12.1%, increasing to 19.9%, 27.7%, and 37.8% in the
      second, third, and fourth quartiles. Intensive care unit length of stay was
      shorter among patients in the first quartile compared with those in the other
      three (p < .001). CONCLUSIONS: This study demonstrates that increasing glycemic
      variability conferred a strong independent risk of mortality in this
      heterogeneous population of critically ill patients. Previously published
      interventional studies of glycemic control may be reinterpreted using the metric
      of glycemic variability. Measures to ensure a low degree of glycemic variability
      may improve outcomes in intensive care unit's implementing glycemic control.
      Finally, ongoing and future investigations should consider including this new
      metric in their study design.

PMID- 18824909
TI  - Rate of reintubation in mechanically ventilated neurosurgical and neurologic
      patients: evaluation of a systematic approach to weaning and extubation.
AB  - OBJECTIVE: To assess whether a systematic approach to weaning and extubation
      (intervention) is superior to the sole physician's judgment (control) in
      preventing reintubation secondary to extubation failure in patients with
      neurologic disorders. DESIGN: Randomized controlled trial. SETTING: Intensive
      care unit of a large teaching hospital. PATIENTS: Three hundred eighteen
      intubated patients who had been receiving mechanical ventilation for at least 12
      hrs and were able to trigger the ventilator. INTERVENTIONS: Patients were
      randomized to the intervention (n = 165) or control group (n = 153).
      MEASUREMENTS: Rate of reintubation after extubation failure occurring within 48
      hrs (primary end point). Duration of mechanical ventilation, length of intensive
      care unit stay, mortality, rate of tracheotomy (secondary end points). The
      perception of the research protocol by the intensive care unit staff was also
      assessed. MAIN RESULTS: The rate of reintubation was lower in the intervention
      (5%) than in the control (12.5%) group (p = 0.047). There was no difference in
      any of the other outcome variables (secondary end points). Simplified Acute
      Physiologic Score II (adjusted odds ratio 1.042 per unit; 95% confidence interval
      1.006-1.080; p = 0.022) and inclusion in the control group (adjusted odds ratio
      2.393; 95% confidence interval 1.000-5.726; p = 0.05) were the only two
      independent predictive factors for the risk of extubation failure. The protocol
      was felt by the staff to determine an improvement in patients' clinical outcome,
      but to increase intensive care unit workload; nurses and physiotherapists
      considered its impact on their professional role more positively than physicians.
      CONCLUSIONS: In patients with neurologic diseases, a systematic approach to
      weaning and extubation reduces the rate of reintubation secondary to extubation
      failure without affecting the duration of mechanical ventilation, and is overall
      positively perceived by intensive care unit professionals.

PMID- 18824910
TI  - Treatment-related risk factors for hospital mortality in Candida bloodstream
      infections.
AB  - OBJECTIVE: To examine the relationship between treatment-related variables for
      Candida bloodstream infection and hospital mortality. DESIGN: Retrospective
      cohort analysis. SETTING: Thousand two hundred-bed academic medical center.
      PATIENTS: A total of 245 consecutive patients with Candida bloodstream infections
      who received antifungal therapy. INTERVENTIONS: Identification of treatment
      related risk factors: central vein catheter retention, inadequate initial
      fluconazole dosing, and delayed administration of antifungal therapy.
      MEASUREMENTS AND MAIN RESULTS: A total of 245 patients with Candida bloodstream
      infections who received antifungal therapy were identified. One hundred eleven
      (45.3%) patients were managed in an intensive care unit and analyzed as a
      separate subgroup. In the hospital cohort, 72 (29.4%) patients died during
      hospitalization and 40 (36.0%) patients died in the intensive care unit cohort.
      In the hospital cohort, logistic regression analysis identified Acute Physiology
      and Chronic Health Evaluation II scores (1-point increments) (adjusted odds ratio
      [AOR], 1.18; 95% confidence interval [CI], 1.11-1.25; p = 0.003), corticosteroid
      use at the time a positive blood culture was drawn (AOR, 3.41; 95% CI, 1.96-5.93;
      p = 0.027), inadequate initial fluconazole dosing (AOR, 3.31; 95% CI, 1.83-6.00;
      p = 0.044), and retention of a central vein catheter (AOR, 4.85; 95% CI, 2.54
      9.29; p = 0.015) as independent determinants of hospital mortality. In the
      intensive care unit cohort, logistic regression analysis identified Acute
      Physiology and Chronic Health Evaluation II scores (1-point increments) (AOR,
      1.21; 95% CI, 1.14-1.29; p = 0.001), inadequate initial fluconazole dosing (AOR,
      9.22; 95% CI, 2.15-19.79; p = 0.004), and retention of a central vein catheter
      (AOR, 6.21; 95% CI, 3.02-12.77; p = 0.011), as independent determinants of
      hospital mortality. For both cohorts the incremental presence of treatment
      related risk factors was statistically associated with greater hospital
      mortality. CONCLUSIONS: Treatment-related factors, including retention of central
      vein catheters and inadequate initial fluconazole dosing, were associated with
      increased hospital mortality in patients with Candida bloodstream infections.
      These data suggest that optimization of initial antifungal therapy and removal of
      central vein catheters may improve the outcomes of patients with Candida
      bloodstream infections.

PMID- 18824911
TI  - Digoxin-specific Fab fragments as single first-line therapy in digitalis
      poisoning.
AB  - OBJECTIVE: Despite administration of Fab fragments in digitalis poisoning, high
      mortality rates are consistently reported. A previous study suggested that Fab
      fragments prescribed as first-line therapy might improve mortality rate. Our
      objective was to evaluate this approach. DESIGN: Retrospective chart review
      (January 1990 to January 2004). SETTING: University hospital intensive care unit.
      PATIENTS: Consecutive patients admitted for cardiac glycoside poisoning.
      INTERVENTION: First-line therapy with Fab fragments (with or without atropine) in
      either curative or prophylactic doses. MEASUREMENTS AND MAIN RESULTS: A total of
      141 patients were admitted for digitalis poisoning of whom 66 received first-line
      Fab fragment therapy. Their median age was 74 years (25th to 75th percentiles: 51
      83); 76% were women. Half were intoxicated by digitoxin and half by digoxin.
      Median serum concentration was 168 (108-205) ng/mL for digitoxin and 6.2 (4.3
      13.5) ng/mL for digoxin. Conduction disturbances were reported in 45 cases (68%)
      and ventricular arrhythmia in six cases (9%). Fab fragments were administered as
      curative treatment in 21 patients (32%) and prophylactically in 45 patients
      (68%). The median cumulative dose was 4 (4-6) vials. No adverse effects were
      reported. Five patients (7.6%) died. CONCLUSIONS: First-line therapy with Fab
      fragments in patients with digitalis poisoning was associated with a low
      mortality rate.

PMID- 18824912
TI  - Ability of pulse power, esophageal Doppler, and arterial pulse pressure to
      estimate rapid changes in stroke volume in humans.
AB  - INTRODUCTION: Measures of arterial pulse pressure variation and left ventricular
      stroke volume variation induced by positive-pressure breathing vary in proportion
      to preload responsiveness. However, the accuracy of commercially available
      devices to report dynamic left ventricular stroke volume variation has never been
      validated. METHODS: We compared the accuracy of measured arterial pulse pressure
      and estimated left ventricular stroke volume reported from two Food and Drug
      Administration-approved aortic flow monitoring devices, one using arterial pulse
      power (LiDCOplus) and the other esophageal Doppler monitor (HemoSonic). We
      compared estimated left ventricular stroke volume and their changes during a
      venous occlusion and release maneuver to a calibrated aortic flow probe placed
      around the aortic root on a beat-to-beat basis in seven anesthetized open-chested
      cardiac surgery patients. RESULTS: Dynamic changes in arterial pulse pressure
      closely tracked left ventricular stroke volume changes (mean r .96). Both devices
      showed good agreement with steady-state apneic left ventricular stroke volume
      values and moderate agreement with dynamic changes in left ventricular stroke
      volume (esophageal Doppler monitor -1 +/- 22 mL, and pulse power -7 +/- 12 mL,
      bias +/- 2 sd). In general, the pulse power signals tended to underestimate left
      ventricular stroke volume at higher left ventricular stroke volume values.
      CONCLUSION: Arterial pulse pressure, as well as, left ventricular stroke volume
      estimated from esophageal Doppler monitor and pulse power reflects short-term
      steady-state left ventricular stroke volume values and tract dynamic changes in
      left ventricular stroke volume moderately well in humans.

PMID- 18824913
TI  - Excessive tidal volume from breath stacking during lung-protective ventilation
      for acute lung injury.
AB  - RATIONALE: Low tidal volume ventilation strategies for patients with respiratory
      failure from acute lung injury may lead to breath stacking and higher volumes
      than intended. OBJECTIVE: To determine frequency, risk factors, and volume of
      stacked breaths during low tidal volume ventilation for acute lung injury.
      DESIGN, SETTING, AND PATIENTS: Prospective cohort study of mechanically
      ventilated patients with acute lung injury (enrolled from August 2006 through May
      2007) treated with low tidal volume ventilation in a medical intensive care unit
      at an academic tertiary care hospital. INTERVENTIONS: Patients were ventilated
      with low tidal volumes using the Acute Respiratory Distress Syndrome Network
      protocol for acute lung injury. Continuous flow-time and pressure-time waveforms
      were recorded. The frequency, risk factors, and volume of stacked breaths were
      determined. Sedation depth was monitored using Richmond agitation sedation scale.
      MEASUREMENTS AND MAIN RESULTS: Twenty patients were enrolled and studied for a
      mean 3.3 +/- 1.7 days. The median (interquartile range) Richmond agitation
      sedation scale was -4 (-5, -3). Inter-rater agreement for identifying stacked
      breaths was high (kappa 0.99, 95% confidence interval 0.98-0.99). Stacked breaths
      occurred at a mean 2.3 +/- 3.5 per minute and resulted in median volumes of 10.1
      (8.8-10.7) mL/kg predicted body weight, which was 1.62 (1.44-1.82) times the set
      tidal volume. Stacked breaths were significantly less common with higher set
      tidal volumes (relative risk 0.4 for 1 mL/kg predicted body weight increase in
      tidal volume, 95% confidence interval 0.23-0.90). CONCLUSION: Stacked breaths
      occur frequently in low tidal volume ventilation despite deep sedation and result
      in volumes substantially above the set tidal volume. Set tidal volume has a
      strong influence on frequency of stacked breaths.

PMID- 18824914
TI  - Impaired baroreflex sensitivity predicts outcome of acute intracerebral
      hemorrhage.
AB  - OBJECTIVE: Impaired blood pressure regulation in the acute phase of stroke has
      been associated with less favorable outcome. Mechanisms and effects of blood
      pressure dysregulation in stroke are not well understood; however, central
      autonomic impairment with sympathetic overactivity and baroreflex involvement are
      discussed. Baroreflex sensitivity (BRS) in spontaneous intracerebral hemorrhage
      has not been investigated. We sought to examine BRS in patients with
      intracerebral hemorrhage and evaluate the relationship between BRS and short-term
      outcome measures. DESIGN: An open, prospective study. SETTING: Neurocritical care
      unit and stroke unit in a university hospital. PATIENTS AND MEASUREMENTS: We
      studied 45 patients with acute intracerebral hemorrhage within 72 hrs from onset
      of symptoms and 38 control subjects. BRS was measured noninvasively using a
      hemodynamic monitoring device. Beat-to-beat blood pressure variability was
      derived. The effects of the BRS, hemorrhage volume, intraventricular blood, and
      admission scores on outcome at 10 days were studied using a multivariate
      regression model. MAIN RESULTS: Compared with the control group, patients with
      intracerebral hemorrhage had significantly decreased BRS (p = 0.002) and
      significantly increased systolic, diastolic, and mean beat-to-beat blood pressure
      variability (p < 0.0001, p = 0.007, p = 0.015). After adjusting for age, National
      Institute of Heath Stroke Scale at admission, volume of intracerebral hemorrhage
      and presence of intraventricular blood in a multivariate regression model, BRS
      gain was an independent predictor of outcome at 10 days. CONCLUSIONS: We found
      that BRS was decreased in patients with acute intracerebral hemorrhage and
      correlated with increased beat-to-beat blood pressure variability. BRS
      independently predicted outcome at 10 days. Modulation of baroreceptor reflex
      sensitivity may represent a new therapeutic target in acute stroke and warrants
      future studies.

PMID- 18824915
TI  - Accuracy of bedside glucose measurement from three glucometers in critically ill
      patients.
AB  - OBJECTIVE: Implementation of strict glucose control in most intensive care units
      has resulted in increased use of point-of-care glucose devices in the intensive
      care unit. The aim of this study was to determine the reliability of point-of
      care testing glucose meters among critically ill patients under intensive insulin
      treatment. DESIGN: Prospective observational study. PATIENTS: Intensive care unit
      and non-intensive care unit patients in a tertiary care teaching hospital.
      MEASUREMENTS: A glucose oxidase method was used to validate the point-of-care
      testing devices. Three different point-of-care testing devices, Accu-Chek Sensor
      (Roche Diagnostics), Precision (Abbott Diagnostics), and HemoCue were tested.
      Glucose measurements were performed in duplicate by an experienced technician
      under standardized conditions in the hospital's laboratory, using arterial
      (intensive care unit patients) and arterial or venous (non-intensive care unit
      patients) heparinized whole blood samples. MAIN RESULTS: A strong correlation was
      found between the glucose oxidase method and the Accu-Chek device (r = .9596, p <
      0.001). Mean absolute difference between the glucose oxidase and Accu-Chek was 
      0.32 mmol/L (95% confidence interval -0.84 to 1.48 mmol/L). Using the
      International Organization for Standardization (ISO) criteria, 27 of 197 samples
      (13.7%) were inaccurate. In all samples that failed to meet the ISO criteria,
      glucose values measured by the Accu-Chek device were higher compared with the
      glucose oxidase method. In another set of experiments among intensive care unit
      patients, strong positive correlations were also found between the other point-of
      care testing devices and the glucose oxidase method. However, paired samples from
      Accu-Chek, HemoCue, and Precision failed the ISO criteria in 9 of 82 (11.0%), 4
      of 82 (4.9%), and 11 of 82 (13.4%) of cases, respectively. In non-intensive care
      unit patients paired samples from Accu-Chek, HemoCue, and Precision failed the
      ISO criteria in 3 of 120 (2.5%), 11 of 120 (9.2%), and 16 of 120 (13.3%) cases,
      respectively. CONCLUSIONS: Under standardized conditions, glucose results from
      three point-of-care testing devices were inaccurate in both intensive care unit
      and non-intensive care unit patients. Among intensive care unit patients,
      inaccurate glucose readings were most frequently falsely elevated, resulting in
      misinterpretation of high glucose values with subsequent inappropriate insulin
      administration or masking of true hypoglycemia.

PMID- 18824916
TI  - Minimal interruption of cardiopulmonary resuscitation for a single shock as
      mandated by automated external defibrillations does not compromise outcomes in a
      porcine model of cardiac arrest and resuscitation.
AB  - OBJECTIVES: Current automated external defibrillations require interruptions in
      chest compressions to avoid artifacts during electrocardiographic analyses and to
      minimize the risk of accidental delivery of an electric shock to the rescuer. The
      earlier three-shock algorithm, with prolonged interruptions of chest
      compressions, compromised outcomes and increased severity of postresuscitation
      myocardial dysfunction. In the present study, we investigated the effect of
      timing of minimal automated external defibrillation-mandated interruptions of
      chest compressions on cardiopulmonary resuscitation outcomes, using a single
      shock algorithm. We hypothesized that an 8-sec interruption of chest compressions
      for a single shock, as mandated by automated external defibrillations, would not
      impair initial resuscitation and outcomes of cardiopulmonary resuscitation.
      DESIGN: Randomized prospective animal study. SETTING: University affiliated
      research laboratory. SUBJECTS: Domestic pigs. MEASUREMENTS AND MAIN RESULTS: In
      24 domestic male pigs weighing 41 +/- 2 kg, ventricular fibrillation was induced
      by left anterior descending coronary artery occlusion and untreated for 7 min.
      Cardiopulmonary resuscitation, including chest compressions and ventilation with
      oxygen, was then performed for an interval of 2 min before attempted
      defibrillation. Animals were randomized into three groups: A) interruption
      immediately before defibrillation; B) interruption after 1 min of cardiopulmonary
      resuscitation; or C) no interruption. Chest compressions were delivered with the
      aid of a mechanical chest compressor at a rate of 100 compressions/min and
      compression/ventilation ratio of 30:2. Defibrillation was attempted with a single
      biphasic 150-J shock. Each animal was successfully resuscitated and survived for
      >72 hr. No differences in the number of shocks before return of spontaneous
      circulation, frequency of recurrent ventricular fibrillation, duration of
      cardiopulmonary resuscitation, and severity of postresuscitation myocardial
      dysfunction were observed. CONCLUSIONS: In this experimental model of cardiac
      arrest and cardiopulmonary resuscitation, minimal automated external
      defibrillation-mandated interruption of chest compressions for a single-shock
      algorithm did not have adverse effects on postresuscitation myocardial or
      neurologic function. All animals, whether subjected to cardiopulmonary
      resuscitation interruptions or not, survived.

PMID- 18824917
TI  - Nitric oxide inhalation and glucocorticoids as combined treatment in human
      experimental endotoxemia.
AB  - OBJECTIVE: Inhaled nitric oxide and glucocorticoids as a combination therapy may
      attenuate endotoxin-induced inflammatory responses in humans as indicated by
      levels of cytokines and clinical signs. Since other authors have shown that
      combined inhaled nitric oxide and steroids improved the histologic damage both in
      pulmonary and systemic organs in a porcine endotoxin model, we examined if an
      anti-inflammatory interaction could be demonstrated in humans. DESIGN: Double
      blind, crossover, placebo-controlled randomized study. SETTING: The intensive
      care unit in a university hospital. SUBJECTS: Fifteen healthy white volunteers (4
      women, 11 men). INTERVENTIONS: Endotoxin (2 ng/kg) was administered
      intravenously. Thirty minutes thereafter the volunteers were given
      glucocorticoids (2 mg/kg) intravenously and inhaled nitric oxide 30 ppm or
      placebo (nitrogen) administered through a nasal cannula. Blood samples and
      clinical signs were collected before and up to 5.5 hrs after the endotoxin
      infusion. MEASUREMENTS AND MAIN RESULT: Following endotoxin body temperature and
      heart rate increased significantly compared with baseline. There were no
      differences observed between the treatments. Endotoxin challenge also markedly
      elevated the plasma levels of tumor necrosis factor-alpha, interleukin (IL)-6, IL
      10, and IL1-ra concentrations during the study period. No difference between
      placebo/glucocorticoids and inhaled nitric oxide/glucocorticoids treatment was
      seen in the cytokine response. CONCLUSIONS: In a human experimental inflammatory
      model using endotoxin, inhaled nitric oxide and glucocorticoids in low doses
      given after the endotoxin challenge did not modify the inflammatory cascade as
      monitored in this study.

PMID- 18824918
TI  - Effect of the chest wall on pressure-volume curve analysis of acute respiratory
      distress syndrome lungs.
AB  - OBJECTIVE: Previously published methods to assess the chest wall effect on total
      respiratory system pressure-volume (P-V) curves in acute respiratory distress
      syndrome have been performed on the lung and chest wall in isolation. We sought
      to quantify the effect of the chest wall by considering the chest wall and lung
      in series. DESIGN: Prospective study. SETTING: Academic health center medical and
      surgical intensive care units. PATIENTS: Twenty-two patients with acute
      respiratory distress syndrome/acute lung injury. INTERVENTIONS: Using a sigmoidal
      equation, we fit the pressure-volume data of the lung alone, and defined for each
      curve the pressure at the point of maximum compliance increase (Pmci), decrease
      (Pmcd), and the point of inflection (Pinf). We calculated the pressure to which
      the total respiratory system must be inflated to achieve a volume that would
      place the lung at each point of interest. We compared these "corrected" pressures
      (Pmci,c, Pmcd,c, and Pinf,c) to the measured values of the total respiratory
      system. MEASUREMENTS AND MAIN RESULTS: The average difference between Pmci and
      Pmci,c was 0.12 cm H2O on inflation (2sd = 5.6 cm H2O) and -1.4 cm H2O on
      deflation (2sd = 5.0 cm H2O); between Pmcd and Pmcd,c was 1.73 cm H2O on
      inflation (2sd = 4.5 cm H2O) and -0.15 cm H2O on deflation (2sd = 4.9 cm H2O);
      and between Pinf and Pinf,c was 0.14 cm H2O on inflation (2sd = 6.7 cm H2O) and 
      0.35 cm H2O on deflation (2sd = 5.0 cm H2O). CONCLUSIONS: This method of
      "correcting" the total respiratory system P-V curve for the chest wall allows for
      calculation of an airway pressure that would place the lung at a desired volume
      on its P-V curve. For most patients, the chest wall had little influence on the
      total respiratory system P-V curve. However, there were patients in whom the
      chest wall did potentially have clinical significance.

PMID- 18824920
TI  - Community planning for pandemic influenza: lessons from the VA health care
      system.
AB  - BACKGROUND: Coordination and communication among community partners-including
      health departments, emergency management agencies, and hospitals-are essential
      for effective pandemic influenza planning and response. As the nation's largest
      integrated health care system, the US Department of Veterans Affairs (VA) could
      be a key component of community planning. PURPOSE: To identify issues relevant to
      VA-community pandemic influenza preparedness. METHODS: As part of a VA-community
      planning process, we developed and pilot-tested a series of tabletop exercises
      for use throughout the VA system. These included exercises for facilities,
      regions (Veterans Integrated Service Networks), and the VA Central Office. In
      each, VA and community participants, including representatives from local health
      care facilities and public health agencies, were presented with a 3-step scenario
      about an unfolding pandemic and were required to discuss issues and make
      decisions about how the situation would be handled. We report the lessons learned
      from these pilot tests. RESULTS: Existing communication and coordination for
      pandemic influenza between VA health care system representatives and local and
      regional emergency planners are limited. Areas identified that would benefit from
      better collaborative planning include response coordination, resource sharing,
      uneven resource distribution, surge capacity, standards of care, workforce
      policies, and communication with the public. CONCLUSIONS: The VA health system
      and communities throughout the United States have limited understanding of one
      another's plans and needs in the event of a pandemic. Proactive joint VA
      community planning and coordination-including exercises, followed by deliberate
      actions to address the issues that arise-will likely improve pandemic influenza
      preparedness and will be mutually beneficial. Most of the issues identified are
      not unique to VA, but are applicable to all integrated care systems.

PMID- 18824919
TI  - Modulation of aquaporin-2/vasopressin2 receptor kidney expression and tubular
      injury after endotoxin (lipopolysaccharide) challenge.
AB  - OBJECTIVE: Sepsis-induced organ dysfunctions remain prevalent and account for
      >50% of intensive care unit admissions for acute renal failure with a mortality
      rate nearing 75%. In addition to the fact that the mechanisms underlying the
      pathophysiology of sepsis-related acute renal failure are unclear, the impact on
      septic-induced acute renal failure of either norepinephrine, a gold-standard
      vasopressor, and arginine vasopressin, a candidate alternative, are not well
      understood. DESIGN: Randomized and controlled in vivo study. SETTING: Research
      laboratory and animal facilities. SUBJECTS: Adult rats treated with endotoxin
      (lipopolysaccharide) and/or vasopressors. INTERVENTIONS: Rats were
      intraperitoneally injected with lipopolysaccharide (12 mg/kg) or saline and then
      infused with either saline, 0.375 microg/microL arginine vasopressin, or 32.5
      microg/microL norepinephrine for 18 hrs. These vasopressor rates yielded
      respective targeted blood levels observed in human septic shock. MEASUREMENTS AND
      MAIN RESULTS: Renal function, including glomerular filtration rate and fraction,
      renal blood flow, aquaporin-2, and arginine vasopressin-2 (V2 receptor)
      networking, water and salt handling, and urinary protein excretion, were
      evaluated. After lipopolysaccharide challenge arginine vasopressin infusion: 1)
      impaired creatinine clearance without affecting renal blood flow, glomerular
      filtration rate, and fraction but reduced free-water clearance, both of which
      being partially restored by the V2 receptor antagonist SR-121463B; 2) decreased
      the recognized ability of arginine vasopressin alone to recruit aquaporin-2 to
      the apical membrane increase its mRNA expression and urinary release; 3)
      increased urinary protein content but decreased specific kidney injury molecule
      1, and Clara cell protein-16 release (p < 0.05 vs. lipopolysaccharide alone).
      Conversely, norepinephrine infusion did not add to lipopolysaccharide-induced
      alteration of urine biochemistry, except for improved creatinine clearance and
      increased microalbuminuria. CONCLUSION: In this endotoxic model, dose-targeted
      arginine vasopressin infusion increased lipopolysaccharide-induced renal
      dysfunction without affecting renal blood flow and glomerular function, but with
      particular disruption of aquaporin-2/V2 receptor networking, consecutive
      decreased salt and water handling ability. This is in clear contrast with
      norepinephrine infusion and suggests specific arginine vasopressin-induced
      "tubular epithelial dysfunction."

PMID- 18824921
TI  - Childhood reactive arthritis.

PMID- 18824922
TI  - Development of autoimmune hepatitis in a child with systemic-onset juvenile
      idiopathic arthritis during therapy with etanercept.

PMID- 18824923
TI  - Maintained efficacy of the tyrosine kinase inhibitor imatinib mesylate in a
      patient with rheumatoid arthritis.

PMID- 18824924
TI  - Hereditary angioedema in a family presenting as transient periarthritis.
AB  - Hereditary angioedema (HAE) is a rare condition known to cause episodic, self
      limiting, nonpruritic, nonpitting edema that involves skin and visceral organs.
      It may affect any external body surface including face, extremities, and
      genitalia. Most commonly involved viscera are gastrointestinal and respiratory
      systems. Patients may have severe abdominal pain because of edema of the bowel
      wall. This disease can cause life threatening laryngeal edema if it involves the
      airway.We describe a patient with HAE who was initially diagnosed with arthritis
      after she had recurrent edema around her peripheral joints. Diagnosis of HAE in
      her led to the same diagnosis in her sister and her father. HAE should be
      considered in the differential diagnosis of recurrent attacks of periarticular
      swelling.

PMID- 18824925
TI  - Devastating skeletal effects of delayed diagnosis of complicated primary
      hyperparathyroidism because of ectopic adenoma.
AB  - Primary hyperparathyroidism is a disease caused by exaggerated secretion of the
      parathyroid gland hormone, produced by an adenoma in 80% of cases. Ectopic
      adenomas occur in a small proportion of cases. Herein, the authors report a 72
      year-old woman with a delayed diagnosis of primary hyperparathyroidism, produced
      by an intrathoracic adenoma, with a longstanding course, presenting with severe
      osteoporosis, multiple fractures, bone deformities, and neurologic impairments.
      Persistent hypercalcemia, high levels of alkaline phosphatase, and parathyroid
      hormone were documented and a paratracheal mass was found on a helicoidal
      tomography of the thorax. After surgical removal, the histopathological
      examination confirmed an ectopic adenoma of the parathyroid gland and the patient
      achieved some improvement in her clinical picture.

PMID- 18824926
TI  - Rituximab for severe refractory pediatric Wegener granulomatosis.
AB  - We describe a case of pediatric Wegener granulomatosis initially treated with
      cyclophosphamide and oral corticosteroids resulting in remission for 5 years. Of
      note in this case is relapse with severe pulmonary disease treated with multiple
      regimens, all unsuccessful. Patient achieved remission with rituximab infusion
      therapy. This demonstrates how rituximab may be beneficial for childhood-onset
      Wegener granulomatosis unresponsive to conventional therapy. The case is followed
      by a review of the current treatment options.

PMID- 18824927
TI  - Musculoskeletal manifestations in liver transplantation recipients.
AB  - BACKGROUND: The prevalence and type of musculoskeletal problems among liver
      transplant recipients have not been well characterized in the current literature.
      OBJECTIVE: We conducted a retrospective analysis of both outpatients and
      inpatients (total 234) who underwent liver transplantation or had rheumatologic
      consultation during 2002-2004, to document the cause for their rheumatologic
      symptoms. We hypothesized that infection, crystal diseases, and corticosteroid
      complications would be more common in this cohort of immunosuppressed patients as
      compared with de novo connective tissue disease. RESULTS: Among the outpatients,
      we found that arthralgia presumably secondary to tacrolimus/sirolimus;
      osteoarthritis, peripheral neuropathy, and myalgia were the most common
      diagnoses. The only autoimmune disease documented was Hepatitis C Virus
      associated cryoglobulinemic vasculitis. Hyperuricemia was also prevalent in this
      patient population. Infection and gout were seen frequently among the inpatients.
      CONCLUSIONS: It is important for physicians to be cognizant of the variety and
      prevalence of musculoskeletal disorders in the liver transplantation patient
      population.

PMID- 18824928
TI  - Higher prevalence of extra-articular manifestations in ankylosing spondylitis
      with peripheral arthritis.
AB  - OBJECTIVE: To study the difference in the clinical presentation of patients of
      ankylosing spondylitis (AS) with and without peripheral arthritis. METHOD: We
      performed a retrospective analysis of case records of 271 AS patients seen in the
      last 15 years at our center and diagnosed as AS according to modified New York
      criteria. We compared clinical features between patients with and without
      peripheral arthritis. RESULTS: There were 253 (93%) men with a M:F ratio of 9:1,
      and 78 (28%) patients had Juvenile onset AS (JAS). Mean age at the disease onset
      was 22.4 +/- 9.3 years. Eighty-four patients had peripheral arthritis. Patients
      with peripheral arthritis had significantly higher prevalence of onset in
      childhood (36% vs. 25% P = 0.04), hip joint involvement (55% vs. 44%, P = 0.04),
      dactylitis (10% vs. 1%, P = 0.0006), enthesitis (28% vs. 7%, P = 0.0006), and
      uveitis (36 vs. 20%, P = 0.005) when compared with patients without peripheral
      arthritis. CONCLUSION: Higher prevalence of juvenile onset and extra-articular
      manifestations in the form of uveitis, dactylitis, and enthesitis in patients
      with peripheral arthritis suggests that this subset of AS might have different
      factors involved in disease pathogenesis.

PMID- 18824929
TI  - Intersession reliability of vertical jump height in women and men.
AB  - The purpose of the present study was to investigate the intersession reliability
      of vertical jump height in women and men recorded from a contact mat. Thirty-five
      women and 35 men performed four testing sessions across a 4-week period, with
      each session separated by 1 week. Within each testing session, subjects completed
      three countermovement vertical jumps (CMJs) for maximum height. Reliability
      statistics were calculated using the highest jump (HIGH) and also from the mean
      of all three jumps (3 MEAN) during each session. Reliability was calculated as a
      change in the mean, coefficients of variation (CVs), and intraclass correlations
      coefficients (ICCs) between testing sessions. For women, jump heights were not
      substantially different between sessions for either the HIGH or 3 MEAN data. The
      CVs for women ranged from 4.4 to 6.6% for HIGH and 4.1 to 6.0% for 3 MEAN, with
      the corresponding ICCs ranging from 0.87 to 0.94 for HIGH and 0.90 to 0.95 for 3
      MEAN. For men, jump heights were not substantially different between sessions for
      HIGH. However, jump heights during session 1 were substantially greater than
      those during session 2 when using the 3 MEAN data. CVs between sessions for HIGH
      ranged from 4.0 to 5.6%, and those for 3 MEAN ranged from 4.2 to 5.2%. The ICCs
      ranged from 0.87 to 0.93 for HIGH and from 0.89 to 0.93 for 3 MEAN. Given the
      maximal nature of vertical jump tests, it seems appropriate to use the highest
      jump from a number of trials for women and men when using a contact mat.
      Practitioners and researchers can use the data to identify the range in which the
      true value of an athlete's score lies and calculate sample sizes for studies
      assessing height during CMJs recorded from a contact mat.

PMID- 18824930
TI  - Acute enhancement of lower-extremity dynamic strength and flexibility with whole
      body vibration.
AB  - The purpose of this investigation was to examine the acute effects of whole-body
      vibration (WBV) on muscular strength, flexibility, and heart rate (HR). Twenty
      adults (10 men, 10 women) untrained to WBV participated in the study. All
      subjects completed assessment of lower-extremity isokinetic torque, flexibility,
      and HR immediately before and after 6 minutes of WBV and 6 minutes of leg cycling
      ergometry (CYL), in randomized order. During WBV, subjects stood upright on a
      vibration platform for a total of 6 minutes. Vibration frequency was gradually
      increased during the first minute to a frequency of 26 Hz, which was maintained
      for the remaining 5 minutes. During CYL, power output was gradually increased to
      50 W during the first minute and maintained at that power output for the
      remaining 5 minutes. Lower-extremity flexibility was determined using the sit-and
      reach box test. Peak and average isokinetic torque of knee extension and flexion
      were measured by means of a motor-driven dynamometer with velocity fixed at 120
      degrees .s. Change scores for the outcome measures were compared between
      treatments using Student's paired t-tests. Analysis revealed significantly
      greater HR acceleration with CYL (24.7 bpm) than after WBV (15.8 bpm). The
      increase of sit-and-reach scores after WBV (4.7 cm) was statistically greater (p
      < 0.05) than after CYL (0.8 cm). After WBV, increases in peak and average
      isokinetic torque of knee extension, 7.7% and 9.6%, were statistically greater
      than after CYL (p < 0.05). Average torque of knee flexion also increased more
      with WBV (+7.8%) than with CYL (-1.5%) (p < 0.05). The findings of this study
      indicate that short-term WBV standing elicits acute enhancements of lower
      extremity muscular torque and flexibility, suggesting the application of this
      technology as a preparatory activity before more intense exercise.

PMID- 18824931
TI  - Effects of caffeine and aspirin on light resistance training performance,
      perceived exertion, and pain perception.
AB  - This study compared independent effects of caffeine and aspirin on muscular
      endurance (repetitions), heart rate (HR), perceived exertion (RPE), and perceived
      pain index (PPI) during light resistance training bouts performed to volitional
      failure. It was hypothesized that the hypoalgesic properties of these ergogenic
      aids would decrease pain perception and potentially result in enhanced
      performance. College-aged men (n = 15) participated in a within-subjects, double
      blind study with three independent, counterbalanced sessions wherein aspirin (10
      mg x kg(-1)), caffeine (6 mg x kg(-1)), or matched placebo were ingested 1 hour
      before exercise, and RPE, HR, PPI, and repetitions (per set and total per
      exercise) were recorded at 100% of individual, predetermined, 12-repetition
      maximum for leg extensions (LE) and seated arm curls (AC). Repeated-measures
      analyses of variance were used for between-trial comparisons. Caffeine resulted
      in significantly greater (p < 0.05) HR (LE and AC), total repetitions (LE), and
      repetitions in set 1 (LE and AC) compared with aspirin and placebo. Aspirin
      resulted in significantly higher PPI in set 1 (LE). In LE, 47% of participants'
      performance exceeded the predetermined effect size (>or= 5 repetitions) for total
      repetitions, with 53% exceeding the effect size (>or= 2 repetitions) for
      repetitions in set 1 with caffeine (vs. placebo). In AC, 53% (total repetitions)
      and 47% (set 1 repetitions) of participants exceeded effect sizes with caffeine
      (vs. placebo), with only 13% experiencing decrements in performance (total
      repetitions). Aspirin also produced a higher PPI and RPE overall and in set 1
      (vs. placebo). This study demonstrates that caffeine significantly enhanced
      resistance training performance in LE and AC, whereas aspirin did not. Athletes
      may improve their resistance training performance by acute ingestion of caffeine.
      As with most ergogenic aids, our analyses indicate that individual responses vary
      greatly.

PMID- 18824932
TI  - Kinetic energy factors in evaluation of athletes.
AB  - It is established that speed and agility are critical attributes of sports
      performance. Performance timing of runs during agility course testing can be used
      to estimate acceleration, speed, or quickness. The authors of this research
      effort also report the energy of motion, or kinetic energy of the athlete, which
      considers not only the speed but also the mass of the athlete. An electronic
      timer was used to determine total run times as well as split performance times
      during a new 60-yd "run-shuttle" test. This newly designed agility test takes
      advantage of the technological capabilities of a laser timing device. Separate
      times for each of four run segments were recorded and converted to average speeds
      (m x s(-1)) as well as a quantitative factor of merit defined as the "K-factor."
      The purpose of this study was to describe the effects of training and to compare
      athletes and teams using measures of time, speed, and kinetic energy. Results of
      the analysis of total time on the 60-yd run-shuttle provided evidence of the
      effectiveness of the training programs. Split times of segments within the 60-yd
      run-shuttle provided information not available from conventional agility tests.
      Average speeds and K-factors identified discriminating characteristics of
      otherwise similar athletes. Our findings support the conclusion that training
      programs and athletic performance may be evaluated using the 60-yd run-shuttle
      with laser timer system. Coaches and trainers may find practical application of
      this technology for American football, soccer, basketball, baseball/softball,
      track and field, and field hockey.

PMID- 18824933
TI  - Relationship of push-ups and sit-ups tests to selected anthropometric variables
      and performance results: a multiple regression study.
AB  - The purpose of this study was to explore whether selected anthropometric measures
      such as specific skinfold sites, along with weight, height, body mass index
      (BMI), waist and hip circumferences, and waist/hip ratio (WHR) were associated
      with sit-ups (SU) and push-ups (PU) performance, and to build a regression model
      for SU and PU tests. One hundred apparently healthy adults (40 men and 60 women)
      served as the subjects for test validation. The subjects performed 60-second SU
      and PU tests. The variables analyzed via multiple regression included weight,
      height, BMI, hip and waist circumferences, WHR, skinfolds at the abdomen (SFAB),
      thigh (SFTH), and subscapularis (SFSS), and sex. An additional cohort of 40
      subjects (17 men and 23 women) was used to cross-validate the regression models.
      Validity was confirmed by correlation and paired t-tests. The regression analysis
      yielded a four-variable (PU, height, SFAB, and SFTH) multiple regression equation
      for estimating SU (R2 = 0.64, SEE = 7.5 repetitions). For PU, only SU was loaded
      into the regression equation (R2 = 0.43, SEE = 9.4 repetitions). Thus, the
      variables in the regression models accounted for 64% and 43% of the variation in
      SU and PU, respectively. The cross-validation sample elicited a high correlation
      for SU (r = 0.87) and PU (r = 0.79) scores. Moreover, paired-samples t-tests
      revealed that there were no significant differences between actual and predicted
      SU and PU scores. Therefore, this study shows that there are a number of
      selected, health-related anthropometric variables that account significantly for,
      and are predictive of, SU and PU tests.

PMID- 18824942
TI  - Thrombophilic risk factors in patients with cranial and spinal dural
      arteriovenous fistulae.
AB  - OBJECTIVE: Numerous studies have reported the technical aspects and results of
      surgical and/or endovascular treatment of cranial dural arteriovenous fistulae
      (cDAVF) and spinal dural arteriovenous fistulae (sDAVF). Only a few of them have
      addressed the question of thrombophilic conditions, which may be relevant as
      pathogenetic factors or can increase the risk for venous thromboembolic events.
      Therefore, the objective of this study is to compare thrombophilic risk factors
      in patients with cDAVF and sDAVF with no history of trauma. METHODS: A total of
      43 patients (25 with cDAVF and 18 with sDAVF) were included in this study. Blood
      samples were analyzed for G20210A mutation of the prothrombin gene and factor V
      Leiden mutation. In all patients, prothrombin time, international normalized
      ratio, fibrinogen, antithrombin, protein C and S activity, von Willebrand factor
      antigen, ristocetin cofactor activity, D-dimer, coagulation factor VIII activity,
      and tissue factor pathway inhibitor were determined. Screening was performed for
      the occurrence of lupus antiphospholipid and cardiolipin antibodies. RESULTS: The
      prevalence of G20210A mutation of the prothrombin gene was significantly higher
      in patients with cDAVF (n = 6) compared with patients with sDAVF (n = 0; P <
      0.05, Fisher's exact test). A factor V Leiden mutation was found in 3 patients
      with sDAVF and in 1 patient with cDAVF (P = 0.29, Fisher's exact test). No
      significant difference was found for other parameters, except for fibrinogen, but
      decreased protein C activity was more frequent in patients with cDAVF compared
      with patients with sDAVF (4 versus 1). Decreased protein S activity was
      encountered in 3 patients (2 with sDAVF and 1 with cDAVF). Cardiolipin antibodies
      were found in 2 patients with cDAVF but in none with sDAVF, whereas only 1
      patient with sDAVF had lupus antiphospholipid antibodies. CONCLUSION: In both
      groups of patients with dural arteriovenous fistulae, genetic thrombophilic
      abnormalities occurred in a higher percentage than in the general population. The
      differences of the genetic abnormalities may be involved in different
      pathophysiological mechanism(s) in the development of these distinct
      neurovascular entities.

PMID- 18824943
TI  - Acute relative adrenal insufficiency after aneurysmal subarachnoid hemorrhage.
AB  - OBJECTIVE: The hypothalamic-pituitary-adrenal axis is an important part of the
      body's natural response to acute illness. Adrenal insufficiency has the potential
      to lead to hemodynamic instability and electrolyte imbalances, limit the body's
      ability to respond to stress, and worsen overall clinical outcome. In this case
      series, we describe 16 patients evaluated for acute adrenal insufficiency after
      aneurysmal subarachnoid hemorrhage. CLINICAL PRESENTATION: Over a 2-year period,
      the medical records of 16 patients admitted to the adult neurosurgery service for
      aneurysmal subarachnoid hemorrhage who were nonresponsive to vasopressor therapy
      and received cosyntropin for the evaluation of adrenal insufficiency within 14
      days of their event were reviewed. INTERVENTION: The median baseline cortisol in
      this population was 22.5 microg/dL, with a poststimulation cortisol level of 31
      microg/dL. Of the population surveyed, a total of 11 patients met the
      preestablished criteria for adrenal insufficiency, 3 with baseline cortisol
      levels of less than 15 microg/dL and 11 with poststimulation concentration
      changes of less than 9 microg/dL. Baseline serum cortisol concentrations were
      significantly correlated with hospital stay (P = 0.045), intensive care unit stay
      (P = 0.005), and ventilator days (P = 0.006). CONCLUSION: To date, this is the
      only investigation evaluating the incidence of acute relative adrenal
      insufficiency in this population. In our cohort, 69% of the patients met the
      preestablished criteria for relative adrenal insufficiency. The impact of low
      dose corticosteroid therapy in this population also needs review, as it could
      have significant implications for the management of cerebral vasospasm.

PMID- 18824944
TI  - Angiographic balloon test occlusion and therapeutic sacrifice of major arteries
      to the brain.
AB  - OBJECTIVE: Treatment of certain cerebral aneurysms, caroticocavernous fistulae,
      and tumors of the neck or cranial base may involve therapeutic arterial
      sacrifice, which requires preoperative knowledge of the feasibility of permanent
      occlusion of the internal carotid artery (ICA) or vertebral artery or arteries.
      METHODS: Retrospective study of transcranial Doppler ultrasonography-monitored
      angiographic balloon test occlusion and therapeutic sacrifice of the ICA or
      vertebral artery. RESULTS: We performed transcranial Doppler-guided balloon test
      occlusion in 136 patients at a procedural risk equivalent to that of conventional
      neuroangiography, and with correct prediction of the hemodynamic result of
      therapeutic arterial sacrifice in all instances. Patients with an immediate drop
      in ipsilateral middle cerebral artery (MCA) velocity to 65% or more of baseline
      values upon ICA balloon occlusion tolerated ICA sacrifice well, whereas
      hemodynamic infarction is likely in those with a corresponding drop in MCA
      velocity to 54% or less. When ICA balloon occlusion caused a drop in MCA velocity
      to between 55 and 64% of baseline, the pulsatility of the MCA signal had to be
      analyzed. Patients who tolerated bilateral vertebral artery closure had reversal
      of flow and an increase in velocity in the P1 section of the posterior cerebral
      artery. In 212 patient-years of observation after therapeutic arterial sacrifice,
      no de novo aneurysms formed. CONCLUSION: Angiographic balloon test occlusion with
      transcranial Doppler monitoring can be performed ultra-swiftly at a risk equal to
      conventional neuroangiography and with correct prediction of the hemodynamic
      outcome of arterial sacrifice. Elective therapeutic arterial occlusion is a safe
      and efficient treatment of large cerebral aneurysms and caroticocavernous
      fistulae.

PMID- 18824946
TI  - Prevalence of pancreatic cystic lesions including intraductal papillary mucinous
      neoplasms in patients with end-stage renal disease on hemodialysis.
AB  - OBJECTIVES: Pancreatic cystic (PC) lesions are not necessarily rare, and it is
      important to diagnose whether PC lesions are neoplastic such as intraductal
      papillary mucinous neoplasm (IPMN) because of its malignant potential. Reports on
      PC lesions in hemodialysis (HD) patients are remarkably limited. The aim of this
      study was to clarify the prevalence and characteristics of PC lesions in HD
      patients. METHODS: We reviewed 1012 consecutive HD patients and 11,100 patients
      (controls) without renal disease who underwent transabdominal ultrasonography
      between January 2003 and December 2005. Patients' sex ratio (female-to-male) was
      less, and the age was older in HD patients. Clinical findings of these patients
      were examined. RESULTS: The prevalence both of PC lesions and IPMNs was
      significantly higher in HD patients than in controls (9.3% vs 1.3% and 2.8% vs
      0.2%, P < 0.0001). The incidence of IPMNs in HD patients with PC lesions was
      higher than that in controls with PC lesions (29.8% vs 17.0%, P = 0.021).
      Multivariate logistic regression analysis revealed that the odds ratios of PC
      lesions and IPMNs were 6.38 (95% confidence interval, 4.82-8.45) and 9.39 (95%
      confidence interval, 5.36-16.49) in HD patients compared with controls.
      CONCLUSION: The prevalence of PC lesions in HD patients is higher, and HD
      patients with PC lesions have high prevalence of IPMNs.

PMID- 18824947
TI  - Citrus fruit intake and pancreatic cancer risk: a quantitative systematic review.
AB  - OBJECTIVES: The purpose of this systematic review was to investigate the
      association between dietary intake of citrus fruits and pancreatic cancer risk.
      METHODS: Authors searched electronic databases and the reference lists of
      publications of studies addressing diet and pancreatic cancer up to December
      2007. All of the epidemiological studies that obtained individual data on dietary
      intake of citrus fruits and presented risk estimates of the association between
      intake of citrus fruits and risk of pancreatic cancer were identified and
      included. Using general variance-based methods, study-specific odds ratios
      (ORs)/relative risk and associated confidence interval (CI)/SE for highest versus
      lowest intake of citrus fruits level were extracted from each article. RESULTS:
      Nine articles including 4 case-control studies and 5 cohort studies proved
      eligible. Overall summary OR using random effect model suggested an inverse
      association in risk of pancreatic cancer with intake of citrus fruits (summary
      OR, 0.83; 95% CI, 0.70-0.98) with large heterogeneity across studies (I = 49.9%).
      CONCLUSIONS: Pooled results from observational studies showed an inverse
      association between intake of citrus fruits and the risk of pancreatic cancer,
      although results vary substantially across studies, and the apparent effect is
      restricted to the weaker study design (case-control studies).

PMID- 18824948
TI  - Effect of nicotine and cigarette smoke on an experimental model of
      intraepithelial lesions and pancreatic adenocarcinoma induced by 7,12
      dimethylbenzanthracene in mice.
AB  - OBJECTIVES: To evaluate the effects of nicotine and cigarette smoke exposure on
      mice submitted to 7,12-dimethylbenzanthracene (DMBA) model of pancreatic
      carcinogenesis. METHODS: One hundred fourteen male mice were divided into the
      DMBA-n and DMBA-s groups: the DMBA-n group was given 2 mg/kg per dose of nicotine
      ([3-(1-methyl-2-pyrrolidinyl)pyridine]) subcutaneously for 45 days, and the DMBA
      s group was exposed to 100 mg/m of cigarette smoke. At day 16, 1 mg of DMBA
      crystals was implanted in the pancreatic head of both groups. Euthanasia was
      performed in all mice 30 days after the surgery. The specimens were evaluated
      according to the following criteria: normal ducts, reactive hyperplasia,
      pancreatic intraepithelial neoplasm 3 (PanIN-3), and carcinoma. For statistical
      analysis, DMBA-exclusive ([DMBA-e] historical control group) was included.
      RESULTS: The frequency of PanIN in the 3 groups was almost the same when
      considering the higher-grade lesions: DMBA-e (16 [66.7%]), DMBA-s (20 [66.7%]),
      and DMBA-n (12 [44.4%]). Pancreatic adenocarcinoma has a higher frequency in the
      DMBA-n group (14 [51.9%]) than in the DMBA-e (4 [16.7%]) and DMBA-s (4, 13.3%)
      groups. The DMBA-s group has the highest score of PanIN-3 (40%). The differences
      among the groups were statistically significant (P = 0.05, Fisher exact test).
      CONCLUSIONS: Nicotine but not cigarette smoke promotes pancreatic DMBA
      carcinogenesis in mice. Pancreatic adenocarcinomas and PanINs have the same
      phenotypic appearance as those that occur in humans.

PMID- 18824949
TI  - Education of patients after whiplash injury: is oral advice any better than a
      pamphlet?
AB  - STUDY DESIGN: Randomized parallel-group trial with 1-year follow-up. OBJECTIVE:
      To evaluate whether education of patients communicated orally by a specially
      trained nurse is superior to giving patients a pamphlet after a whiplash injury.
      SUMMARY OF BACKGROUND DATA: Long-lasting pain and physical disability after
      whiplash injuries are related to both serious personal suffering and huge socio
      economic costs. Pure educational interventions after such injuries seem generally
      as effective as more costly interventions, but it is unknown if the way advice is
      communicated is of any importance. METHODS: Participants with relatively mild
      complaints after car collisions were recruited from emergency departments and
      GPs. A total of 182 participants were randomized to either: (1) a 1 hour
      educational session with a specially trained nurse, or (2) an educational
      pamphlet. Outcome parameters were neck pain, headache, disability, and return to
      work. Recovery was defined as scoring pain 0 or 1 (0-10 point scale) and not
      being off sick at the time of the follow-ups. RESULTS: After 3, 6, and 12 months
      60%, 58%, and 66%, respectively of the participants had recovered. Group
      differences were nonsignificant on all outcome parameters, even though the
      outcome tended to be better for the group receiving personal advice. CONCLUSION:
      Prognosis did not differ between patients who received personal education and
      those who got a pamphlet. However, a systematic tendency toward better outcome
      with personal communicated information was observed and the question how patients
      should be educated to reduce the risk of chronicity after whiplash is worth
      further investigation, since no treatment have been proven to prevent long
      lasting symptoms, and all forms of advice or educational therapy are so cheap
      that even a modest effect justifies its use.

PMID- 18824950
TI  - Direct application of the TNF-alpha inhibitor, etanercept, does not affect CGRP
      expression and phenotypic change of DRG neurons following application of nucleus
      pulposus onto injured sciatic nerves in rats.
AB  - STUDY DESIGN: Immunohistological and behavioral analysis of the effect of a tumor
      necrosis factor alpha (TNF-alpha) inhibitor in an injured-nerve model. OBJECTIVE:
      To examine the effect of direct application of a TNF-alpha inhibitor (etanercept)
      on injured-nerve pain caused by nucleus pulposus. SUMMARY AND BACKGROUND DATA:
      TNF-alpha is thought to play a crucial role in radicular pain. Calcitonin gene
      related peptide (CGRP) is an inflammatory neuropeptide found in small sensory
      neurons. We have reported that CGRP appears in medium and large dorsal root
      ganglion (DRG) neurons that transmit proprioception in physiologic conditions.
      The purpose of the current study was to examine the change in behavior and
      phenotypic change of CGRP-immunoreactive DRG neurons by the TNF-alpha inhibitor,
      etanercept, in a disc herniation model. METHODS: For the injured-nerve model,
      nucleus pulposus was applied to the sciatic nerve and the sciatic nerve pinched.
      Saline (10 microL; n = 10), as a control, or etanercept (150 microg: n = 10) were
      applied to sciatic nerves simultaneously. Mechanical allodynia was examined.
      Immunohistochemistry was used to examine CGRP expression in L5 DRGs. RESULTS:
      Significant mechanical allodynia for 10 days was seen in the injured-nerve group
      compared with sham-operated animals. Etanercept ameliorated the mechanical
      allodynia slightly on day 2; however, there was no effect on other days. CGRP
      immunoreactivity was upregulated in the L5 DRG neurons of injured-nerve groups
      compared with the sham-operated group (P < 0.01). However, etanercept did not
      affect CGRP expression after nerve injury (P > 0.05). Proportions of CGRP-
      immunoreactive medium and large neurons were not significantly different in the
      nerve injury + saline group compared with the injury + etanercept group (P >
      0.05). CONCLUSION: Our results indicate that direct application of a TNF-alpha
      inhibitor had a small effect on acute pain behavior and may not be effective for
      suppression of inflammatory peptides in the current disc-herniation model.

PMID- 18824951
TI  - Responsiveness of a patient specific outcome measure compared with the Oswestry
      Disability Index v2.1 and Roland and Morris Disability Questionnaire for patients
      with subacute and chronic low back pain.
AB  - STUDY DESIGN: A prospective cohort. OBJECTIVE: The aim of this study was to
      compare the responsiveness of a patient specific outcome measure with the
      Oswestry Disability Index v2.1 (ODI) and the Roland and Morris Disability
      Questionnaire (RMDQ) for patients with mild to moderate subacute and chronic low
      back pain. SUMMARY OF BACKGROUND DATA: Patient specific outcome measures allow
      individuals to select and rate the relative importance of activities they
      consider of greatest relevance. However, there is a paucity of research reporting
      the responsiveness of these measures for patient with back pain. METHODS: Two
      hundred and one patients were assessed at baseline and 12 months using the
      patient specific activity questionnaire (PSAQ), the ODI, the RMDQ, and a
      transition rating scale. The latter was used to categorize patients into 3 groups
      (better, same or worse). Effect size statistics, receiver operating
      characteristic curves and 1-way between groups analysis of variance were used in
      the analysis. RESULTS: All instruments were able to detect improvements in back
      pain as measured by the transition rating scale. In this improved group effect
      sizes were large for the PSAQ (1.08 to 1.31) and ODI (-0.88 to -1.00) but only
      moderate for the RMDQ (-0.70 to -0.74). In the deteriorated group effect sizes
      were moderate to large for the ODI (0.61 to 1.16) and RMDQ (0.69 to 1.25), but
      small for the PSAQ (-0.16 to -0.26). The areas under receiver operator
      characteristic curves for the ODI, PSAQ, and RMDQ, respectively were: 0.75 (95%
      CI 0.68 to 0.82), 0.75 (95% CI 0.68 to 0.82) and 0.69 (95% CI 0.61 to 0.76).
      CONCLUSION: The PSAQ was highly responsive to change in patients who report
      improvement in back symptoms but unlike the ODI and RMDQ was unable to detect
      deterioration. Overall, the ODI was more responsive than either the PSAQ or the
      RMDQ.

PMID- 18824952
TI  - Effect of spironolactone, potassium canrenoate and their common metabolite
      canrenone on serum digoxin measurement by digoxin III, a new digoxin immunoassay.
AB  - Spironolactone and potassium canrenoate (aldosterone antagonist diuretics) are
      often used with digoxin in clinical practice. It has been well documented in the
      literature that spironolactone, potassium canrenoate, and their common metabolite
      canrenone cross-react with several digoxin immunoassays at concentrations
      expected after therapeutic usage of these drugs and falsely elevate or lower
      serum digoxin concentrations. Recently, Abbott Laboratories marketed a new
      Digoxin III immunoassay for application on the AxSYM analyzer. We studied the
      potential interference of these compounds with this new digoxin assay. The Tina
      quant assay was used as the reference method because spironolactone, potassium
      canrenoate, and canrenone do not interfere with serum digoxin measurement using
      this assay. Aliquots of drug-free serum were supplemented with therapeutic and
      above therapeutic concentrations of spironolactone, canrenone, and potassium
      canrenoate, and apparent digoxin concentrations were measured using the Digoxin
      III assay and Tina-quant assay. Significant apparent digoxin concentrations were
      observed when the Digoxin III digoxin assay was used, but no apparent digoxin
      levels was observed using the Tina-quant assay. When serum pools prepared from
      patients receiving digoxin were further supplemented with these compounds in
      concentrations expected in sera of patients receiving these medications, falsely
      elevated digoxin levels were observed using Digoxin III assay, but no
      statistically significant change was observed using the Tina-quant assay. We
      conclude that spironolactone, potassium canrenoate, and their common metabolite
      canrenone interfere with the serum digoxin measurements using the new Digoxin III
      assay.

PMID- 18824953
TI  - Differential effects of factor IIa inhibitors on the endogenous thrombin
      potential.
AB  - Calibrated automated thrombin generation measurement in clotting plasma
      (endogenous thrombin potential, ETP) is being used increasingly to monitor the
      effects of anticoagulant drugs. Calibrated automated thrombography measures the
      concentration of thrombin in clotting plasma by monitoring the cleavage of a
      fluorogenic substrate (Z-Gly-Gly-Arg-7-amino-4-methylcoumarin) and comparing it
      with a constant known thrombin activity in a parallel nonclotting sample. This
      study compared the concentration-dependent effects of different factor IIa
      inhibitors on the ETP. In accordance with a theoretical prediction, the
      monovalent factor IIa inhibitors melagatran and argatroban reduced peak thrombin
      concentrations without a marked effect on the lag time of thrombin generation.
      However, both bivalent factor IIa inhibitors lepirudin and bivalirudin markedly
      prolonged the lag time of thrombin generation and thus behaved like "super"
      factor Xa inhibitors according to the theoretical model. These findings have
      important consequences for therapeutic drug monitoring using thrombin generation
      assays. For monitoring of hirudins, the lag time of thrombin generation seems to
      be a very sensitive parameter. In contrast, for monitoring of argatroban, the
      evaluation of the ETP seems to be useful.

PMID- 18824954
TI  - Therapeutic drug monitoring of ziprasidone in a clinical treatment setting.
AB  - There is limited information on the pharmacokinetics ofziprasidone (ZIP) in
      naturalistic clinical settings. The objective of this study was to investigate
      the concentrations of ZIP and its active metabolite S-methyl-dihydroziprasidone
      (SMDZ), and the dose-normalized concentrations, using routine therapeutic drug
      monitoring (TDM) data. A high-performance liquid chromatographic method for
      determining serum concentrations of these substances for routine clinical use was
      established at the TDM Laboratory in Linkoping, Sweden. This analytical service
      was available to all physicians in Sweden. Between January 2001 and December
      2004, 545 analyses, representing samples from 370 patients, were performed. The
      median daily ZIP dose was 120 mg (range 20 -320 mg). In all, 121 steady-state
      trough specimens with essential clinical information were included in the
      pharmacokinetic evaluation. The median (25th to 75th percentile) serum
      concentration of ZIP was 125 nmol/L (82-188 nmol/L). The SMDZ:ZIP ratio decreased
      with increasing serum concentration of ZIP. The median (25th to 75th percentile)
      dose-normalized concentrations (nmol L(-1) mg(-1) d(-1) forZIPand SMDZ were 1.13
      (0.74-1.77) and 0.62 (0.45-0.86), respectively,with SMDZ:ZIP ratio of 0.57 (0.42
      0.79). The overall coefficients of variation for dose-normalized serum
      concentrations of ZIP, SMDZ, andSMDZ:ZIP ratio were 62%, 56%, and 57%,
      respectively (n = 121). Smoking women had lower normalized ZIP concentrations
      than nonsmoking women. Twenty-eight patients with repeated eligible TDM analyses
      were studied for intraindividual variance over time. In summary, great
      interindividual and intraindividual differences in ZIPconcentrations were
      observed. TDM of ZIP maybe used for individual dose adjustments and monitoring
      medication adherence.

PMID- 18824955
TI  - Intoxications due to ingestion of gamma-butyrolactone: organ distribution of
      gamma-hydroxybutyric acid and gamma-butyrolactone.
AB  - In Europe, the misuse of gamma-hydroxybutyric acid (GHB) and its analogues has
      increased within the recent years. Here, 2 fatalities and 1 nonfatal intoxication
      resulting from ingestion of gamma-butyrolactone (GBL), a precursor of GHB, are
      presented. GHB was quantified involving the conversion to GBL by application of a
      gas chromatography-mass spectrometry (GC/MS) method. Besides quantitation of GHB
      equivalents ("total GBL"), all specimens of case 1 were analyzed for the
      metabolic precursor GBL itself (absolute GBL). The cause of death in each case
      was attributed to GHB intoxication; the manner of death was suicide in the first
      case and accidental in the second one. Another yet nonfatal GHB intoxication was
      reported by an emergency department concerning a 36-year-old woman who was
      hospitalized due to her comatose state and loss of adverse effects reflexes. Here
      nail polish remover pads were used as source for GBL.

PMID- 18824956
TI  - An HPLC-PDA method for the simultaneous quantification of the HIV integrase
      inhibitor raltegravir, the new nonnucleoside reverse transcriptase inhibitor
      etravirine, and 11 other antiretroviral agents in the plasma of HIV-infected
      patients.
AB  - A new method using high-performance liquid chromatography coupled with photo
      diode array detection was developed and validated for the quantification of
      plasma concentrations of the human immunodeficiency syndrome integrase inhibitor
      raltegravir (RGV), the new nonnucleoside reverse transcriptase inhibitor
      etravirine (ETV), and 11 other antiretroviral agents: ritonavir, atazanavir,
      lopinavir, nevirapine, efavirenz, saquinavir, indinavir, nelfinavir, and its
      metabolite M-8, amprenavir, and darunavir. A simple solid phase extraction
      procedure was applied to 500 microL aliquots of plasma, and chromatographic
      separation of the drugs and internal standard (quinoxaline) was achieved with a
      gradient (acetonitrile and phosphate buffer) on an C-18 reverse-phase analytical
      column with a 28-minute analytical run time. Calibration curves were optimized
      according to expected ranges of drug concentrations in patients, and the
      coefficient of determination (r) was higher than 0.998 for all analytes. Mean
      intraday and interday precisions (percent relative SD) for all compounds were
      3.67% and 6.39%, respectively, and mean accuracy (percent deviation from nominal
      concentration) was -1.17%. Extraction recovery ranged within 75% and 83% for all
      drugs analyzed. The solid phase extraction and high-performance liquid
      chromatography coupled with photo diode array method described allow a specific,
      sensitive, and reliable simultaneous determination of RGV, ETV, and 11
      antiretroviral agents in plasma by a single assay. Good extraction efficiency and
      low limit of quantification make this a suitable method for use in clinical
      trials and for therapeutic drug monitoring of RGV, protease inhibitors, and
      nonnucleoside reverse transcriptase inhibitors, including ETV.

PMID- 18824958
TI  - Simultaneous unilateral moyamoya disease and ipsilateral dural arteriovenous
      fistula: case report.
AB  - OBJECTIVE: Previous reports have described an association between moyamoya
      disease and arteriovenous malformations, but this unusual case is the first
      report of a unilateral moyamoya pattern simultaneously associated with an
      ipsilateral dural arteriovenous fistula (dAVF). CLINICAL PRESENTATION: A 44-year
      old man presented with headache, tinnitus, and an intraventricular hemorrhage, as
      seen on computed tomographic scans. Cerebral angiography showed a right moyamoya
      pattern and an ipsilateral dAVF fed by branches of the external carotid artery
      and draining into the transverse sinus. INTERVENTION: After the intraventricular
      hemorrhage resolved, the patient underwent transarterial embolization of the dAVF
      with Onyx (EV3, Inc. Irvine, CA), followed by a direct superficial temporal
      artery-to-middle cerebral artery bypass. Subsequent reconstitution of the dAVF
      required transvenous embolization, which obliterated the dAVF. At his 2-month
      follow-up examination, the patient was asymptomatic and neurologically intact.
      CONCLUSION: Recent investigations have established that both moyamoya disease and
      dAVFs are associated with dural angiogenesis. These factors may represent a
      mechanism for vaso-occlusive ischemia contributing to the formation of dAVF. This
      extremely rare coincidental presentation may have deeper pathogenic implications.

PMID- 18824959
TI  - Large cerebellar hemorrhage during trumpet playing: importance of blood pressure
      elevation during the valsalva maneuver: case report.
AB  - OBJECTIVE: The authors report a case of a large intracerebellar hemorrhage that
      occurred in a professional musician while playing the trumpet. This is the first
      report of such a complication. CLINICAL PRESENTATION: A 60-year-old man presented
      with severe occipital headache accompanied by nausea, vomiting, and dizziness
      that occurred while he was practicing the trumpet. On presentation, he was
      hypertensive with a systolic blood pressure of 255 mmHg and was found to have a
      large left cerebellar hemorrhage. INTERVENTION: Magnetic resonance imaging and
      magnetic resonance angiography were performed but revealed no tumor or vascular
      abnormality. The patient was initially stable but, despite maximal medical
      therapy, deteriorated and was taken to the operating room for suboccipital
      craniectomy and evacuation of the hematoma. CONCLUSION: This patient likely had
      chronic hypertension; however, the transient increase in systolic blood pressure
      associated with intensive trumpet playing and the Valsalva maneuver may have
      contributed to his risk of hemorrhage. We suggest that hypertensive screening and
      therapy may be especially important in this population and emphasize the
      importance for neurosurgeons to understand the physiology involved in the
      Valsalva maneuver.

PMID- 18824960
TI  - Recurrent cerebellar hemangioblastoma with enhancing tumor in the cyst wall: case
      report.
AB  - OBJECTIVE: Hemangioblastomas are the most common primary intra-axial tumors of
      the adult posterior fossa and the tumors most often associated with von Hippel
      Lindau disease. Resection of cerebellar hemangioblastomas involves tumor excision
      and drainage of associated cysts. The cyst wall is considered devoid of tumor
      cells and is not excised. We present an unusual variant of a hemangioblastoma
      that showed pathological evidence of a tumor within the cyst wall that correlated
      with radiographic cyst wall enhancement in a patient with a recurrent
      hemangioblastoma. CLINICAL PRESENTATION: A 38-year-old woman with von Hippel
      Lindau disease presented with a recurrent cerebellar hemangioblastoma despite two
      previous operations during which the mural nodule was removed but the cyst wall
      was not. Magnetic resonance imaging showed a cystic lesion with an enhancing
      mural nodule with atypical nodular enhancement throughout the cyst wall.
      INTERVENTION: Because the patient had a history of multiple recurrences, gross
      total resection of the mural nodule and cyst wall was performed. At surgery,
      neovascularization and neoplasia within the cyst wall were visualized.
      Histopathological examination showed a capillary hemangioblastoma with tumor
      tissue inside the cyst wall. No clinical or radiographic evidence of recurrence
      was observed during 2 years of follow-up monitoring. CONCLUSION: This unusual
      case of a hemangioblastoma with cyst wall enhancement demonstrates a correlation
      between enhancement on magnetic resonance imaging and presence of neoplasia
      within the cyst wall, as well as the importance of considering complete resection
      of these areas, including the cyst wall, for the prevention of recurrence.

PMID- 18824961
TI  - Thoracic spinal cord compression by intramedullary hamartomatous tissue in a
      young boy: case report.
AB  - OBJECTIVE: Spinal cord hamartomas are a rare occurrence characterized by well-
      differentiated mature elements located in an irregular position in the spinal
      cord. CLINICAL PRESENTATION: The authors present the unique case of a 12-year-old
      boy who originally presented to our center for treatment of a right thalamic
      astrocytoma. One year after his initial presentation, the child developed
      progressive bilateral leg weakness with decreased sensation. Spinal magnetic
      resonance imaging performed at this time revealed an intramedullary spinal cord
      lesion from T4 to T8, which was later found to be composed of hamartomatous
      tissue. INTERVENTION: The patient underwent bilateral T4 to T8 laminectomies with
      subtotal resection of the hamartomatous lesion, and his symptoms improved
      postoperatively. CONCLUSION: Although typically described in the literature as
      spinal cord hamartomas because of their histological composition, these rare
      hamartomatous lesions may be the result of a neurulation defect rather than true
      hamartomas. In patients presenting with multiple neurological conditions, as in
      our case, diagnosis may be more complex. For those presenting with neurological
      signs and symptoms, surgical treatment is essential.

PMID- 18824963
TI  - Toward the emergence of nanoneurosurgery: part III-nanomedicine: targeted
      nanotherapy, nanosurgery and progress toward the realization of nanoneurosurgery.

PMID- 18824965
TI  - Treatment options for third ventricular colloid cysts: comparison of open
      microsurgical versus endoscopic resection.

PMID- 18824967
TI  - Detection of caspase-3, neuron specific enolase, and high-sensitivity C-reactive
      protein levels in both cerebrospinal fluid and serum of patients after aneurysmal
      subarachnoid hemorrhage.

PMID- 18824969
TI  - Percutaneous transforaminal lumbar interbody fusion for the treatment of
      degenerative lumbar instability.

PMID- 18824971
TI  - The sphenoparietal sinus.

PMID- 18824973
TI  - Objectifying when to halt a boxing match: a video analysis of fatalities.

PMID- 18824975
TI  - Techniques of posterior C1-C2 stabilization.

PMID- 18824977
TI  - Single nucleotide polymorphisms of tissue inhibitors of metalloproteinase genes
      in familial moyamoya disease.

PMID- 18824982
TI  - Neurosurgery and big science.

PMID- 18824986
TI  - Microsurgical clipping and endovascular coiling of intracranial aneurysms: a
      critical review of the literature.
AB  - OBJECTIVE: Although endovascular coiling has been used for 15 years in the
      treatment of intracranial aneurysms, fewer than 60 published studies have
      directly compared microsurgical clipping and endovascular coiling, and only two
      studies have used a randomized, prospective design. The objective of this review
      is to weigh evidence for the efficacy of endovascular coiling compared with
      microsurgical clipping based on published head-to-head comparisons. METHODS: Two
      major electronic databases, PubMed and Cochrane Library, were queried using
      search terms such as "coiling," "clipping," "microsurgical," "endovascular,"
      "Guglielmi," and "intracranial aneurysm." Relevant randomized trials and
      observational, cohort, and case studies of unruptured and ruptured aneurysms were
      considered for analysis. Data from included studies were summarized
      qualitatively, addressing study methodologies, patient demographics, study
      techniques/equipment, and outcome measures. RESULTS: Forty-seven studies were
      included in the final count, including two prospective randomized trials, 23
      prospective observational studies, 20 retrospective observational studies, and
      two studies that used a combination of prospective and retrospective data. In
      total, 18 studies found outcomes to be equivalent in the coiled and clipped
      groups, 18 studies favored coiling, 10 studies favored clipping, and one study
      had no conclusion (in terms of a comparison). CONCLUSION: The earliest randomized
      prospective study by Koivisto et al. found clinical and angiographic results
      between the two methodologies to be statistically equivalent. The more recent and
      larger randomized, prospective study from the International Subarachnoid Aneurysm
      Trial group suggests that endovascular coiling is statistically superior to
      microsurgical clipping in clinical outcomes, although the recently published long
      term follow-up of International Subarachnoid Aneurysm Trial patients documents
      higher recurrence and rehemorrhage rates after endovascular coiling. Although
      there is no clear consensus in these two studies or in the 45 observational
      studies included, clinically useful information can be extracted to improve
      shared decision making and interaction between interventionalists and
      neurosurgeons, create more individualized treatment algorithms, and enhance
      future research.

PMID- 18824987
TI  - The utility of onyx for preoperative embolization of cranial and spinal tumors.
AB  - OBJECTIVE: To assess the utility, technical factors, and complications associated
      with the use of Onyx (Micro Therapeutics, Inc., Irvine, CA) for preoperative
      embolization of cranial and spinal tumors. METHODS: We reviewed a prospectively
      accumulated database for patients in whom Onyx was used for preoperative
      embolization of cranial and spinal tumors over a 19-month period. The patients'
      demographic characteristics, tumor type and location, embolic agents used,
      arteries catheterized, and associated complications were assessed. Specific
      attention was focused on technical factors associated with the use of Onyx that
      differed from the use of other commonly used embolic materials. RESULTS: Ten
      patients (four female and six male; age range, 11-60 yr) underwent preoperative
      embolization with Onyx before cranial or spinal tumor resection. Tumors included
      three juvenile nasal angiofibromas, two meningiomas, two hemangioblastomas, two
      metastases (renal cell and thyroid), and one giant cell tumor. Onyx embolization
      was performed in 43 vessels over 11 treatment sessions. There were no
      complications related to the embolization procedures. Deep penetration of the
      embolic agent into the tumor was documented through preoperative imaging or
      surgical pathological specimens. CONCLUSION: Preoperative embolization of cranial
      and spinal tumors can be performed safely. Specific technical advantages of Onyx
      included deep penetration of lesions producing extensive tumor infarction, the
      ability to embolize extensive portions of the tumors through fewer arterial
      catheterizations, and the safety of catheter withdrawal despite often substantial
      reflux along the embolic catheter.

PMID- 18824988
TI  - Multimodality treatment of brain arteriovenous malformations with microsurgery
      after embolization with onyx: single-center experience and technical nuances.
AB  - OBJECTIVE: To report our experience with the treatment of brain arteriovenous
      malformations (AVM) with microsurgical resection after embolization with Onyx
      liquid embolic agent (eV3, Irvine, CA). METHODS: Between August 2005 and December
      2006, 28 patients were treated by the same surgical-endovascular team. Twenty
      eight AVMs were embolized preoperatively in 55 sessions (71 pedicles) with Onyx.
      We analyzed the AVM size, volume, number of embolization sessions, degree of
      preoperative obliteration, time to embolization and resection after the bleed,
      intraprocedural complications, intraoperative blood loss, other complications,
      and postoperative outcome at 6 months. Technical nuances of the embolization and
      surgical resection of the embolized AVMs are illustrated in illustrative cases.
      RESULTS: The average size and volume of AVMs treated with Onyx were 3.56 cm
      (largest, 7.6 cm), and 13.03 ml, respectively. The average Spetzler-Martin grade
      was 2.75. The average preoperative volumetric obliteration was 74.1%. The average
      blood loss during resection of embolized AVMs was 348 ml. Complications related
      to embolization were stuck microcatheter (two patients), proximal vessel
      perforation (one patient), and anterior choroidal territory stroke (one patient).
      Surgical complications included wound infection (one patient), residual AVM nidus
      (one patient), normal pressure perfusion breakthrough with worsening of
      neurological deficit caused by embolization (one patient), and new-onset motor
      deficits in five patients. At the time of the 6-month follow-up examination, four
      patients with new-onset motor deficits had recovered completely or nearly
      completely, and one patient was disabled. One patient died, never recovering from
      the initial poor condition due to the bleed. Pathological examination of resected
      AVMs showed angionecrosis in 42.9%, foreign body giant cells in 39.3%, and
      evidence of recanalization of Onyx-embolized vessels in 14.3% of specimens.
      CONCLUSION: Multimodality treatment with microsurgery is safe and effective after
      embolization with Onyx. High occlusion rates and low complication rates were
      observed after Onyx embolization and were comparable to those in previous
      reports. Superselective intranidal or perinidal catheter positions and slow,
      controlled injections that protect the draining veins make the therapy safe even
      in complex AVMs and critical locations. We recommend resection of the AVM despite
      apparently complete embolization with Onyx. Team work and coordination between
      the surgeon and the interventional neuroradiologist are important to achieve a
      good outcome.

PMID- 18824989
TI  - Surgical management of unruptured intracranial aneurysms that are inappropriate
      for endovascular treatment: experience based on two academic centers.
AB  - OBJECTIVE: To analyze the results of the surgical management of unruptured
      intracranial aneurysms (UIA) when coil embolization (CE) was considered first but
      deemed inappropriate by our multidisciplinary groups. METHOD: In two
      institutions, all UIAs recommended for treatment were considered first for a CE
      procedure if accessibility, neck width, and fundus-to-neck ratio were
      appropriate. Patients with UIAs considered inappropriate for CE were to undergo a
      surgical clipping procedure. We reviewed the medical records of all patients who
      underwent surgical clipping between February 1996 and February 2006. RESULTS: A
      total of 325 patients with 440 UIAs were treated. Of them, 149 patients were
      selected by our multidisciplinary staff for treatment by CE, and 176 patients
      with 238 UIAs were treated by 207 surgical procedures. Angiographic studies
      revealed complete occlusion in 95% and near total occlusion in 2.5% of surgically
      treated UIAs. No deaths related to surgery occurred. Sixteen patients (9.1%)
      experienced postoperative complications, four of which persisted 1 year after
      surgery (two cases of diplopia and two aphasic disorders). The 1-year morbidity
      rate was 2.2% (four of 176) by patient and 1.7% (four of 238) by aneurysm. For
      UIAs smaller than 10 mm in patients younger than 65 years old, the morbidity rate
      was 0.56%. CONCLUSION: Our results gathered from two centers with the same
      management of UIAs show that SC remains a safe and effective treatment for UIAs
      even when CE is considered first.

PMID- 18824990
TI  - The current role of microsurgery for posterior circulation aneurysms: a selective
      approach in the endovascular era.
AB  - OBJECTIVE: During the past decade, management of posterior circulation aneurysms
      has shifted away from microsurgery. Currently, microsurgical clipping is
      considered a primary, competitive alternative to endovascular coiling, or more
      commonly, a secondary alternative when endovascular therapy is unfavorable. We
      present a large, multidisciplinary team experience with posterior circulation
      aneurysms in an institution that continues to use microsurgery as a primary
      treatment modality for selected aneurysms. METHODS: During a 9-year period, 217
      patients with 228 posterior circulation aneurysms were treated microsurgically;
      they included 106 basilar bifurcation, 27 posterior cerebral artery, 23 superior
      cerebellar artery, eight anteroinferior cerebellar artery, five basilar trunk, 47
      posteroinferior cerebellar artery, and 12 vertebral artery aneurysms. Overall,
      81% of patients presented with hemorrhage, and 33% of the aneurysms were large or
      giant in size. RESULTS: Direct clipping was performed in 75% of cases, and the
      overall rate of angiographic aneurysm obliteration was 98.1%. Sixteen patients
      (7.4%) died after surgery, 25 patients (11.5%) experienced transient neurological
      deterioration, and 17 patients (7.8%) experienced permanent neurological
      deterioration. At late follow-up (mean duration, 13.6 mo), 144 patients had good
      outcomes (Glasgow Outcome Scale scores of 5 or 4, 66%), and 184 patients (85%)
      either improved or were unchanged relative to their preoperative baseline.
      Overall, mean Glasgow Outcome Scale scores improved from 3.60 to 3.97.
      CONCLUSION: Despite increasing reliance on endovascular therapy with posterior
      circulation aneurysms, there is a role for microsurgical therapy. Microsurgery
      remains a competitive, primary therapy for superior cerebellar artery, P1
      posterior cerebral artery, distal anteroinferior cerebellar artery, and
      posteroinferior cerebellar artery aneurysms. Microsurgery has become a secondary
      therapy for P2 posterior cerebral artery, basilar trunk, proximal anteroinferior
      cerebellar artery, vertebrobasilar junction, and vertebral artery aneurysms when
      endovascular therapy is unfavorable. The preferred therapy for basilar
      bifurcation aneurysms remains unclear. Collaborative, multidisciplinary teams are
      strengthened and results are improved by offering competitive treatment
      alternatives for patients to consider and select. Rather than abandoning the
      posterior circulation prematurely, aneurysm surgeons should maintain technical
      proficiency with these lesions.

PMID- 18824991
TI  - Norepinephrine and cerebral blood flow regulation in patients with arteriovenous
      malformations.
AB  - OBJECTIVE: To test the hypothesis that the sympathetic nervous system plays a
      role in cerebral blood flow regulation in patients with arteriovenous
      malformations (AVM). METHODS: Cortical interstitial norepinephrine was measured
      by means of microdialysis, regional cerebral blood flow was measured by a thermal
      diffusion technique, and regional oxygen saturation (SO2) was measured by
      microspectrophotometry in 12 patients harboring cerebral AVMs (AVM group) and in
      15 patients with deep-seated nonvascular lesions (control group) before and after
      resection. Measurements were compared according to groups and times of
      measurements. All values are given as means +/- standard deviation. RESULTS:
      Cortical regional SO2 increased significantly (P < 0.05) in both groups after
      surgery (AVM group: presurgery 52.4 +/- 12.5% SO2, postsurgery 71.4 +/- 7.4% SO2;
      control group: presurgery 57.1 +/- 8.4% SO2, postsurgery 69.9 +/- 8.7% SO2),
      whereas regional cerebral blood flow increased only in the AVM group (AVM group:
      presurgery 18.9 +/- 6.6 ml/100 g/min, postsurgery 26.2 +/- 6.9 ml/100 g/min;
      control group: presurgery 20.1 +/- 7.6 ml/100 g/min, postsurgery 19.4 +/- 7.8
      ml/100 g/min). Norepinephrine concentrations were significantly lower in the AVM
      group as compared with the control group before surgery. Although there was no
      significant difference between pre- and postsurgery conditions in the AVM group,
      the norepinephrine level of the control group was significantly lower after
      surgery (AVM group: presurgery 3.3 +/- 1.2 nmol/L, postsurgery 2.9 +/- 1.7
      nmol/L; control group: presurgery 5.4 +/- 1.4 nmol/L, postsurgery 4.2 +/- 1.1
      nmol/L). CONCLUSION: Chronically lowered perfusion pressure seems to induce the
      hypothesized adaptive down-regulation of sympathetic nervous system activity, yet
      protective up-regulation after a sudden elevation of cerebral perfusion pressure
      after AVM excision could not be shown in this study.

PMID- 18824992
TI  - Gamma knife radiosurgery for acromegaly: outcomes after failed transsphenoidal
      surgery.
AB  - OBJECTIVE: This study evaluates the safety and efficacy of gamma knife
      radiosurgery (GKRS) in patients with a growth hormone-secreting adenoma. METHODS:
      A retrospective review of data collected from a prospective database of GKRS
      patients between January 1988 and September 2006 was performed in patients with
      acromegaly. Successful endocrine outcome was defined as normalization of the
      insulin-like growth factor level. Tumor volume was also assessed. At least 18
      months of follow-up was available in 95 patients who received radiosurgery during
      the study period. Mean endocrine follow-up was 57 months (range, 18-168 mo).
      RESULTS: Normal insulin-like growth factor levels were achieved in 50 patients
      (53%) at an average time of 29.8 months after radiosurgery (median, 23.5 mo). A
      decrease in tumor volume control was achieved in 83 (92%) of 90 patients. Five
      patients (6%) had no change in tumor volume, and two patients (2%) had an
      increase in tumor volume. New endocrine deficiencies developed in 32 patients
      (34%). Four patients developed new-onset partial visual acuity deficits; three of
      these patients had received previous conventional fractionated radiation therapy.
      CONCLUSION: GKRS is a complementary treatment for recurrent or residual growth
      hormone-secreting pituitary adenomas. Although infrequent, tumor growth, new
      onset pituitary hormone deficiency, recurrence, and neurological dysfunction
      require careful clinical, radiological, and endocrinological follow-up.

PMID- 18824993
TI  - Pituitary tumor type affects the chance of biochemical remission after
      radiosurgery of hormone-secreting pituitary adenomas.
AB  - OBJECTIVE: Reported biochemical remission rates have ranged widely after
      stereotactic radiosurgery for patients with hormone-secreting pituitary adenomas.
      Confounding variables include histology, radiation dose, use of pituitary
      suppressive medications, and length of follow-up. METHODS: A retrospective review
      of 46 patients with pituitary adenomas (growth hormone-secreting, n = 27;
      prolactin-secreting, n = 11; adrenocorticotropin-secreting, n = 8) undergoing
      radiosurgery between January 1990 and December 2003 was conducted. All received a
      tumor margin dose of 18 Gy or more and were off pituitary-suppressive medications
      for at least 1 month before radiosurgery. The groups were similar with regard to
      irradiated volume, radiation dose, and follow-up. The median endocrinological
      follow-up after radiosurgery was 54 months. RESULTS: The 4-year remission rates
      were 87% for patients with Cushing's disease, 67% for patients with acromegaly,
      and 18% for patients with prolactinomas. Patients with oversecretion of
      adrenocorticotropin or growth hormone were more likely to achieve remission after
      radiosurgery than patients with prolactinomas (hazard ratio, 4.4; 95% confidence
      interval, 1.1-18.2; P = 0.04). Of 44 patients with normal or partial anterior
      pituitary function before radiosurgery, 16 (36%) developed one or more new
      anterior pituitary deficits. The incidence of new anterior pituitary deficits was
      26% at 4 years. No differences were noted in the incidence of new anterior
      deficits among the groups. CONCLUSION: There seems to be a differential
      sensitivity after radiosurgery for hormone-secreting pituitary adenomas.
      Remission rates are greater for patients with Cushing's disease and acromegaly,
      whereas radiosurgery is less effective in achieving biochemical remission for
      patients with prolactinomas.

PMID- 18824994
TI  - Intramedullary spinal ependymomas: analysis of a consecutive series of 82 adult
      cases with particular attention to patients with no preoperative neurological
      deficit.
AB  - OBJECTIVE: Surgery should be considered for patients with intramedullary spinal
      ependymomas (ISE), particularly those presenting with a neurological deficit
      preoperatively. In contrast, it is still a debatable matter whether to recommend
      the same approach for patients with no neurological impairment. To investigate
      this matter, we analyzed the data of 82 consecutive patients with ISEs treated at
      our institution. METHODS: We reviewed the medical charts of all ISE patients
      undergoing operation at our institution between 1985 and 2000. Particular
      attention was given to patients without neurological deficit before surgery.
      RESULTS: Eighty-two consecutive ISE patients were included in this study.
      Preoperatively, a neurological deficit of variable severity was present in 72
      patients (Group A, 88%) and absent in 10 patients (Group B, 12%). In the latter
      group, seven patients had progressive and nonspecific pain as the only presenting
      symptom; two had arm dysesthesias; and in one patient, ISE was diagnosed
      incidentally. The mean duration of their symptoms was 21 months. We achieved a
      total tumor excision in nine patients and subtotal removal in one. At the last
      follow-up assessment (mean, 45 mo), all Group B patients remained at Grade I of
      the McCormick classification, except one, who deteriorated to Grade Ib.
      Furthermore, nonspecific pain diminished in three patients, stabilized in four,
      and worsened in one. Arm dysesthesias diminished in one patient and stabilized in
      the other. No surgery-related complication or recurrence was recorded in these
      patients. CONCLUSION: Surgery should be carefully considered for ISE patients
      with no objective neurological deficit preoperatively because, in our experience,
      it resolves their preoperative complaints in 30% of cases, stabilizes them in
      60%, and worsens them in 10%.

PMID- 18824995
TI  - Temporal window of metabolic brain vulnerability to concussion: a pilot 1H
      magnetic resonance spectroscopic study in concussed athletes--part III.
AB  - OBJECTIVE: In the present study, the occurrence of the temporal window of brain
      vulnerability was evaluated in concussed athletes by measuring N-acetylaspartate
      (NAA) using proton magnetic resonance (H-MR) spectroscopy. METHODS: Thirteen
      nonprofessional athletes who had a sport-related concussive head injury were
      examined for NAA determination by means of H-MR spectroscopy at 3, 15, and 30
      days postinjury. All athletes but three suspended their physical activity. Those
      who continued their training had a second concussive event and underwent further
      examination at 45 days from the initial injury. The single case of one
      professional boxer, who was studied before the match and 4, 7, 15, and 30 days
      after a knockout, is also presented. Before each magnetic resonance examination,
      patients were asked for symptoms of mild traumatic brain injury, including
      physical, cognitive, emotional, and sleep disturbances. Data for H-MR
      spectroscopy recorded in five normal, age-matched, control volunteers, who were
      previously screened to exclude previous head injuries, were used for comparison.
      Semiquantitative analysis of NAA relative to creatine (Cr)- and choline (Cho)
      containing compounds was performed from proton spectra obtained with a 3-T
      magnetic resonance system. RESULTS: Regarding the values of the NAA-to-Cr ratio
      (2.21 +/- 0.11) recorded in control patients, singly concussed athletes, at 3
      days after the concussion, showed a decrease of 18.5% (1.80 +/- 0.04; P < 0.001).
      Only a modest 3% recovery was observed at 15 days (1.88 +/- 0.1; P < 0.001); at
      30 days postinjury, the NAA-to-Cr ratio was 2.15 +/- 0.1, revealing full
      metabolic recovery with values not significantly different from those of control
      patients. These patients declared complete resolution of symptoms at the time of
      the 3-day study. The three patients who had a second concussive injury before the
      15-day study showed an identical decrease of the NAA-to-Cr ratio at 3 days (1.78
      +/- 0.08); however, at 15 days after the second injury, a further diminution of
      the NAA-to-Cr ratio occurred (1.72 +/- 0.07; P < 0.05 with respect to singly
      concussed athletes). At 30 days, the NAA-to-Cr ratio was 1.82 +/- 0.1, and at 45
      days postinjury, the NAA-to-Cr ratio showed complete recovery (2.07 +/- 0.1; not
      significant with respect to control patients). This group of patients declared a
      complete resolution of symptoms at the time of the 30-day study. CONCLUSION:
      Results of this pilot study carried out in a cohort of singly and doubly
      concussed athletes, examined by H-MR spectroscopy for their NAA cerebral content
      at different time points after concussive events, demonstrate that also in
      humans, concussion opens a temporal window of brain metabolic imbalance, the
      closure of which does not coincide with resolution of clinical symptoms. The
      recovery of brain metabolism is not linearly related to time. A second concussive
      event prolonged the time of NAA normalization by 15 days. Although needing
      confirmation in a larger group of patients, these results show that NAA
      measurement by H-MR spectroscopy is a valid tool in assessing the full cerebral
      metabolic recovery after concussion, thereby suggesting its use in helping to
      decide when to allow athletes to return to play after a mild traumatic brain
      injury.

PMID- 18824996
TI  - Minor head trauma in soccer and serum levels of S100B.
AB  - OBJECTIVE: To compare the serum levels of S100B after head trauma with the effect
      of heading, high-intensity exercise, and playing in a league match. Heading and
      head trauma in soccer have been suspected to cause brain impairment. The protein
      S100B is a marker of acute neuronal tissue damage. METHODS: Baseline S100B was
      measured in 535 Norwegian professional soccer players. Two hundred twenty-eight
      head impacts were registered from 352 league matches. Three teams (n = 48)
      performed a high-intensity exercise session without heading and a low-intensity
      session with heading exercises. A blood sample was drawn from each participant
      within 1 hour (B1) after the session, and another sample (B12) was drawn after a
      match or training session. The players were assigned to four groups: Head Impact
      (n = 65), Match Control (match participants without head impact, n = 49), High
      intensity Exercise (n = 35), and Heading (n = 36). RESULTS: Serum S100B increased
      from baseline to B1 for all groups. The increase for the match groups (Head
      Impact and Match Control) was significantly higher than for both training groups.
      However, no significant differences between the Head Impact and Match Control
      groups or between the two training groups were found. A total of 39 players
      (33.9%) had elevated B1 values (>/=0.12 ng/ml) after a match, but these findings
      were equally distributed between the Match Control and Head Impact groups.
      CONCLUSION: Both soccer training and soccer matches cause a transient increase in
      S100B. There is a possible additive effect of activity with high intensity and
      heading, but minor head impacts do not seem to cause an additional increase.

PMID- 18824997
TI  - Outcome of Chiari-associated syringomyelia after hindbrain decompression in
      children: analysis of 49 consecutive cases.
AB  - OBJECTIVE: Chiari I malformation is complicated by syringomyelia in many cases.
      Hindbrain decompression remains first-line surgical treatment; however, the
      incidence, time course, and predictors of syrinx resolution remain unclear. We
      set out to determine predictors of syrinx improvement after hindbrain
      decompression for Chiari I- associated syringomyelia. METHODS: Forty-nine
      consecutive pediatric patients undergoing posterior fossa decompression for
      Chiari I-associated syringomyelia were followed with serial magnetic resonance
      imaging evaluations postoperatively. Clinical, radiological, and operative
      variables were assessed as predictors of syrinx improvement as a function of time
      using Kaplan-Meier plots and log-rank analysis. RESULTS: Mean patient age was 11
      +/- 5 years. Syringomyelia was symptomatic in 39 (80%) and asymptomatic in 10
      (20%) cases. Twenty-one (54%) patients experienced symptom resolution (median, 4
      mo postoperatively). Twenty-seven (55%) patients experienced radiographic
      improvement in syringomyelia (median, 14 mo postoperatively). After hindbrain
      decompression, motor symptoms were associated with a 2.35 increased hazard ratio
      for symptom improvement (P = 0.031) versus all other symptoms. Among patients
      with sensory deficits, dysesthesia was associated with a 3.12 increased hazard
      ratio for symptom improvement (P = 0.032) versus symptoms of paresthesia or
      anesthesia. CONCLUSION: In our experience, just more than one-half of patients
      with Chiari- associated syringomyelia demonstrated clinical and radiographic
      improvement after hindbrain decompression. Median time to radiographic
      improvement lagged behind clinical improvement by 10 months. Motor symptoms were
      more likely to improve with hindbrain decompression. Paresthesia or anesthesia
      symptoms were less likely to improve with hindbrain decompression. These findings
      may help guide surgical decision making and aid in patient education.

PMID- 18824998
TI  - Three-dimensional volumetrics for tracking vestibular schwannoma growth in
      neurofibromatosis type II.
AB  - OBJECTIVE: Vestibular schwannomas (VS) are common, benign, VIIIth cranial nerve
      tumors. Treatment in patients with the genetic disorder neurofibromatosis type II
      (NF2) is complicated by their development of bilateral VS and risk of complete
      deafness. Intervention decisions consider several clinical factors including
      tumor size and growth rate evaluated using magnetic resonance imaging. The
      current study evaluated the relative sensitivity of volumetric versus linear
      diameter measurement for assessing VS growth rate and progression. METHODS:
      Retrospective analysis was performed on 43 magnetic resonance imaging scans
      acquired longitudinally (range, 2-7 yr) from 10 patients with NF2. Fifteen VS
      were measured (five patients had unilateral lesions meeting inclusion criteria)
      using both maximum linear diameter and semiautomated volumetric analysis.
      Progression was defined according to Response Evaluation Criteria in Solid Tumors
      and its volumetric (cubed linear) equivalent. Measurement techniques were
      compared by assessing sensitivity to lesion growth. RESULTS: Volumetric measures
      were significantly more sensitive to VS growth, both for total change and change
      per year percentages; cubed linear growth measures (proportional to volume
      growth) underestimated volume growth by 50%. Seven lesions showed progression on
      volumetric analysis, but two of these did not show progression based on linear
      measures. Thus, for 29% of lesions showing progression based on volume, linear
      measures did not detect progression. CONCLUSION: Linear measurements
      underestimate VS growth rate compared with volumetric measures in NF2 patients.
      These results provide clear, quantitative proof that diameter measures are not as
      sensitive to change as volumetric measurements and that volumetric measurements
      should be strongly considered when making VS treatment decisions.

PMID- 18824999
TI  - Importance of screening logs in clinical trials for severe traumatic brain
      injury.
AB  - OBJECTIVE: The primary intent for obtaining screening logs in a randomized
      clinical trial is to assess selection bias in patient recruitment. This is
      particularly relevant to focused trials in heterogeneous populations such as
      traumatic brain injury (TBI) patients. We aimed to investigate the benefits of
      collecting screening logs in two randomized clinical trials conducted in TBI.
      METHODS: Screening logs were collected as part of the conduct of two multicenter
      trials of neuroprotective agents in TBI: the Salzburg Atherosclerosis Prevention
      Program in Subjects at High Individual Risk study (n = 924) and the dexanabinol
      study (n = 861). Centers were requested to submit monthly information on all
      patients with TBI admitted to the intensive care unit, including demographics,
      time of injury and admission, injury severity, and, if not recruited, the
      reason(s) for exclusion. RESULTS: In the Salzburg Atherosclerosis Prevention
      Program in Subjects at High Individual Risk study, 52 centers submitted admission
      data on 4166 patients. In the dexanabinol trial, 96 centers submitted data on
      7052 patients. On average, only 20% of patients screened for the Salzburg
      Atherosclerosis Prevention Program in Subjects at High Individual Risk study and
      10% for the dexanabinol trial were enrolled. The main reasons for exclusion were
      neurological status (29 and 26%, respectively), age (24 and 30%, respectively),
      and admission outside of the time window (17 and 21%, respectively). Differences
      in patient characteristics between screened and enrolled patients, with
      substantial country-specific variation, were observed. CONCLUSION: The collection
      of screening logs is necessary to report trial results according to the
      Consolidated Standards of Reporting Trials guidelines and to assess the
      generalizability of findings. Our experience shows the feasibility of collecting
      screening logs and illustrates how the potential for selection bias may creep
      into well-designed randomized clinical trials as a result of factors outside the
      control of investigators. Consistency and accuracy in screening log completion
      may further serve as an early indicator of center performance in a trial.

PMID- 18825000
TI  - Clinical problem-solving: brachial plexus closed injury and reconstruction.
AB  - OBJECTIVE: Current management of severe brachial plexus injury has undergone
      recent modifications, and surgical options have expanded. METHODS: The case of a
      man with a severe closed brachial plexus injury resulting from a motorcycle
      accident is presented. The patient is found to have upper root avulsions that
      deprive him of function in the proximal arm. RESULTS: Pre-, intra-, and
      postoperative decision making is reviewed by an expert in peripheral nerve
      surgery. Attention is paid to both diagnosis and management. A brief review of
      the literature pertaining to these points follows. CONCLUSION: The recent
      expansion of surgical options for the management of severe brachial plexus injury
      has introduced significant controversy into this field.

PMID- 18825002
TI  - Role of antifibrotic cytokine interferon-gamma in the prevention of
      postlaminectomy peridural fibrosis in rats.
AB  - OBJECTIVE: Extensive peridural fibrosis after spinal surgery may be the
      underlying cause of failed-back syndrome in some cases. There is increasing
      evidence that generation of specific cytokine patterns by immune and structural
      cells and interactions among these cells mediate many of the key events involved
      in fibrogenesis. Interferon-gamma (IFN-gamma) has several potential antifibrotic
      actions, including inhibition of fibroblast proliferation and collagen
      deposition, promotion of fibroblast apoptosis, and inhibition of production and
      action of the fibrogenic cytokine, transforming growth factor-beta. We conducted
      a study to determine the effectiveness of IFN-gamma in preventing postlaminectomy
      peridural fibrosis in rats. To the best of our knowledge, this is the first study
      testing immunotherapy in peridural fibrosis. Type 2 cytokine hypothesis of
      fibrogenesis is emphasized. METHODS: Laminectomies were performed in 30 rats. We
      administered 2000 U/d IFN-gamma, 20,000 U/d IFN-gamma, or 0.2 ml/d saline to the
      laminectomy site through a silicone catheter for 3 days in blinded fashion. The
      amount of scar tissue, fibroblast density, inflammatory cell density, arachnoidal
      involvement, and bone regeneration were analyzed histologically. RESULTS:
      Histopathological examination showed a significantly reduced amount of scar
      tissue and fibroblast density in the low-dose IFN-gamma group compared with the
      control and high-dose IFN-gamma groups. A significant increase was detected in
      inflammatory cell density in the high-dose IFN-gamma group compared with the
      control and low-dose IFN-gamma groups. CONCLUSION: Cytokines play a critical role
      in wound healing, tissue repair, and fibrogenesis. This study suggests that
      topical application of low-dose IFN-gamma is an effective and safe method of
      preventing peridural fibrosis, but further studies with different doses,
      durations, and intervals are required to achieve better results.

PMID- 18825001
TI  - Evidence of inflammatory cell involvement in brain arteriovenous malformations.
AB  - OBJECTIVE: Brain arteriovenous malformations (AVM) have high matrix
      metalloproteinase-9, interleukin-6, and myeloperoxidase (MPO) expression, and
      polymorphic variations in inflammatory genes are associated with an increased
      risk of hemorrhage. In this study, we characterized the presence of inflammatory
      cells in AVM lesional tissue specimens. METHODS: Immunohistochemistry was used to
      identify and localize neutrophils (MPO as marker), macrophages/microglia (CD68 as
      marker), T lymphocytes (CD3 as marker), and B lymphocytes (CD20 as marker).
      Endothelial cell (EC) marker CD31 was used as an index to assess vascular mass
      (EC mass). Surgical specimens from 20 unruptured, nonembolized AVMs were
      examined; seven cortical samples from temporal lobectomy were used as controls.
      Positive signals for inflammatory cell markers were counted and analyzed by
      normalizing to the area of the tissue section and the amount of endothelial cells
      (cells/mm/EC mass pixels). Levels of MPO and matrix metalloproteinase 9 were
      determined by enzyme-linked immunosorbent assay. RESULTS: Neutrophils and
      macrophages are all frequently identified in the vascular wall of AVM tissue. In
      contrast, T and B lymphocytes are rarely observed in AVM tissue. AVM tissue
      displayed more neutrophil and macrophage/microglia markers than epilepsy control
      tissue (MPO: 434 +/- 333 versus 5 +/- 4, P = 0.0001; CD68: 454 +/- 404 versus 4
      +/- 2, P = 0.0001; cells/mm/EC mass pixels). In ex vivo studies, neutrophil
      quantity, MPO, and matrix metalloproteinase-9 levels were all colinear (R = 0.98
      0.99). CONCLUSION: Our study demonstrates that inflammatory cells are present in
      AVM tissue. Taken together with previous genetic and cytokine studies, these data
      are consistent with a novel view that inflammation is associated with AVM disease
      progression and rupture.

PMID- 18825003
TI  - Neural connectivity maps: then and now.

PMID- 18825004
TI  - The history of neurosurgery at Emory University in Atlanta, Georgia.
AB  - The development of neurosurgery at Emory University has paralleled the evolution
      of the science and practice of neurosurgery during the 20th century. This article
      features those individuals who have influenced and nurtured neurosurgery at
      Emory. It discusses the contributions of Crawford W. Long and further traces the
      development of the Emory University School of Medicine and Grady Memorial
      Hospital. Those individuals who have led neurosurgery at Emory are emphasized.
      Finally, the current Emory Department of Neurosurgery is featured, including
      facilities, faculty, and areas of subspecialty expertise.

PMID- 18825005
TI  - Contributions of Johann jacob Huber to the surface anatomy of the spinal cord and
      meninges.
AB  - From prehistoric times, man has been aware that injury to the spine may result in
      paralysis of the limbs; this is reflected in bas-relief figures found at Nineweh
      in ancient Mesopotamia, in a hunting scene that depicts a lioness wounded by King
      Ashurbanipal. The Edwin Smith papyrus gives many case illustrations of spinal
      cord injury resulting in paralysis, yet early physicians were unaware of the
      anatomy of the spinal cord. Galen performed prospective studies in animals by
      sectioning the spinal cord at varying levels and observing the commensurate
      paralysis and sensory loss. Real advances in the understanding of spinal cord
      anatomy did not occur until human cadaveric dissections were undertaken; even
      then, the knowledge of the anatomy of the spinal cord lagged behind that of other
      body structures. Johann Jacob Huber appears to be the first anatomist to focus on
      the spinal cord almost exclusively. His descriptions, and especially his
      illustrations that depict spinal cord surface anatomy, are impressive with regard
      to their accuracy and their sense of photorealism. Indeed, his illustrations seem
      to compare well with the anatomic drawings in contemporary anatomic texts. Yet,
      we were unable to find a single article in the entire English-language literature
      depicting his illustrations. We conclude that the description and anatomic
      illustrations by Johann Jacob Huber remain a hidden gem in the history of human
      spinal anatomy.

PMID- 18825126
TI  - Large-scale evaluation of protein reductive methylation for improving protein
      crystallization.

PMID- 18825128
TI  - Classical genetics goes high-tech.

PMID- 18825127
TI  - A pilot project to generate affinity reagents to human proteins.

PMID- 18825130
TI  - Form follows function: lymphoid tissue microarchitecture in antimicrobial immune
      defence.
AB  - Secondary lymphoid organs (SLOs) are tissues that facilitate the induction of
      adaptive immune responses. These organs capture pathogens to limit their spread
      throughout the body, bring antigen-presenting cells into productive contact with
      their cognate lymphocytes and provide niches for the differentiation of immune
      effector cells. Therefore, the microanatomy of SLOs defines the ability of an
      organism to respond to pathogens. SLO microarchitecture is, at the same time,
      extremely adaptable to environmental changes. In this Review, we discuss recent
      insights into the function and plasticity of the SLO microenvironment with
      regards to antimicrobial immune defence.

PMID- 18825131
TI  - The multifaceted contributions of leukocyte subsets to atherosclerosis: lessons
      from mouse models.
AB  - Chronic inflammation drives the development of atherosclerosis, and details
      regarding the involvement of different leukocyte subpopulations in the pathology
      of this disease have recently emerged. This Review highlights the surprising
      contribution of granulocyte subsets and mast cells to early atherogenesis and
      subsequent plaque instability, and describes the complex, double-edged role of
      monocyte, macrophage and dendritic-cell subsets through crosstalk with T cells
      and vascular progenitor cells. Improved understanding of the selective
      contributions of specific cell types to atherogenesis will pave the way for new
      targeted approaches to therapy.

PMID- 18825132
TI  - Are female lower urinary tract symptoms alleviated by alpha-adrenoreceptor
      antagonists?
AB  - This commentary discusses the article by Low and colleagues, who studied the
      effect of terazosin in women with lower urinary tract symptoms (LUTS) and an
      International Prostate Symptom Score (IPSS) > o =8. Terazosin therapy
      significantly improved IPSS quality-of-life scores and King's Health
      Questionnaire scores. These findings might seem surprising, because previous
      studies have shown that alpha-adrenoreceptor antagonists are not effective in
      women with overactive bladder, which is considered the most common form of LUTS
      in females. Many women have voiding symptoms, however, and the inclusion criteria
      in this study resulted in a different population profile compared with those of
      other studies of female LUTS. The mechanism behind the effect of terazosin is
      unclear. Without urodynamic characterization, it cannot be established whether
      patients in the study were obstructed, or whether the effect of terazosin was
      related to a decrease in bladder outflow resistance.

PMID- 18825133
TI  - Comparison of coronary revascularization procedures in octogenarians: a
      systematic review and meta-analysis.
AB  - BACKGROUND: Elderly patients are the fastest growing population in the US
      healthcare system and more patients aged 80 years and older require CABG or
      percutaneous coronary intervention (PCI) for coronary revascularization than ever
      before. Because octogenarian patients have not been adequately represented in
      randomized trials comparing CABG and PCI, the most appropriate method of
      revascularization for this group of patients has not been determined. METHODS: We
      performed a systematic review and a meta-analysis of 66 studies of coronary
      revascularization in patients aged over 80 years. The primary endpoints included
      30 day mortality and long-term survival. Subgroup analyses stratified by
      revascularization type (PCI versus CABG) were also performed. RESULTS: Pooled
      estimate of 30 day mortality was 6.3% (95% CI 5.3%-7.5%), and for survival at 1,
      3 and 5 years, 86% (84%-88%), 78% (74%-81%) and 67% (61%-72%), respectively. A
      greater number of men (P <0.001) and patients with multivessel disease (P =
      0.004) were treated with CABG than with PCI. Pooled estimates, based on type of
      revascularization, of 30 day mortality and 1 year survival were similar (7.3%
      [6.3%-8.2%] for CABG vs 5.4% [4.4%-6.4%] for PCI and 86% [83%-88%] for CABG vs
      87% [84%-91%] for PCI, respectively). CONCLUSIONS: Available data indicate that
      revascularization can be performed in octogenarians with acceptable short-term
      and long-term outcomes; most of the evidence is, however, low level. Furthermore,
      it is unclear whether octogenarians derive greater survival benefit from CABG or
      from PCI because preprocedural risk profiles differ between intervention types.
      Periprocedural and long-term outcomes are, however, equivalent, and randomized,
      controlled trials of high-risk octogenarians are needed.

PMID- 18825134
TI  - Dietary antioxidants in inflammatory arthritis: do they have any role in etiology
      or therapy?
AB  - Rheumatoid arthritis is an autoimmune-mediated inflammatory disease of unknown
      etiology, and is characterized by joint pain and soft-tissue swelling. The role
      of dietary antioxidants in the prevention and amelioration of symptoms in
      inflammatory joint disease has been of interest for many years. Epidemiological
      studies provide evidence of a link between dietary antioxidant intake and the
      likelihood of developing inflammatory arthritis. Interventional studies of
      antioxidant supplementation in established disease have been inconclusive
      overall; however, the quality of such studies has often been poor. The pathways
      by which antioxidant compounds might act are now better understood. In this
      Review, we explore not only some of the accepted mechanisms of antioxidant
      function but also outline some concepts that could aid further investigation of
      the potential therapeutic role of dietary antioxidants in inflammatory arthritis.

PMID- 18825135
TI  - A case of macrophage activation syndrome successfully treated with anakinra.
AB  - BACKGROUND: A 13-year-old girl presented with features typical of systemic
      juvenile idiopathic arthritis, including fever, rash and arthritis. Her past
      medical history was unremarkable. INVESTIGATIONS: Routine investigations,
      including CBC, serological tests for urea and electrolyte levels, tests of liver
      function and clotting, measurement of erythrocyte sedimentation rate, cultures of
      blood, urine and throat swabs, abdominal ultrasonography, echocardiography, bone
      marrow aspiration, and determination of laboratory parameters, including presence
      of anti-streptolysin O antibody and levels of C-reactive protein, lactate
      dehydrogenase, serum ferritin, D-dimer, fibrinogen and ciclosporin. Specialized
      investigations included measurement of serum levels of interleukin (IL)-1, IL-6,
      IL-10, tumor necrosis factor and soluble CD25. DIAGNOSIS: Systemic juvenile
      idiopathic arthritis complicated by macrophage activation syndrome. MANAGEMENT:
      The disease remained active following treatment with intravenous steroid,
      immunoglobulin and ciclosporin. The patient's disease was successfully controlled
      following the introduction of anakinra.

PMID- 18825137
TI  - Is megestrol acetate a suitable option for treatment of hot flashes in women with
      breast cancer?
AB  - Chemotherapy for breast cancer is associated with the development of hot flashes,
      which can cause the patient considerable discomfort. Estrogen replacement therapy
      alleviates the number and severity of hot flashes but is contraindicated in such
      cases. Alternative methods to treat hot flashes are, therefore, urgently needed.
      Goodwin et al. have performed a 6-month, double-blind, randomized, placebo
      controlled trial of megestrol acetate in 286 women with breast cancer. After 3
      months, 65% of the patients receiving 20 mg megestrol acetate daily had achieved
      an appreciable reduction in the number of hot flashes (> or = 75% from baseline),
      compared with 48% in the 40 mg megestrol acetate group and 14% in the placebo
      group. The positive effects of megestrol acetate on hot flash frequency were
      maintained at 6 months. In this Practice Point commentary, I discuss the key
      findings of Goodwin et al. and place them into clinical context, highlighting the
      need for additional studies of hormonal therapies in women with breast cancer.

PMID- 18825138
TI  - Insulin therapy versus cell-based therapy for type 1 diabetes mellitus: what lies
      ahead?

PMID- 18825139
TI  - Should the levothyroxine starting dose be tailored to disease severity in
      neonates with congenital hypothyroidism?
AB  - Early levothyroxine treatment is crucial to minimize neurocognitive impairment
      associated with congenital hypothyroidism. In this Practice Point commentary, I
      discuss the findings, implications, and limitations of the study of Mathai et al.
      in which neonates with congenital hypothyroidism were treated with variable
      initial doses of levothyroxine. A high initial levothyroxine dose was used for
      newborn babies with athyreosis, an intermediate dose for those with ectopic
      glands, and a low dose for those with dyshormonogenesis. Serum free T(4) levels
      normalized within 2 weeks, but serum TSH levels within up to 4 weeks. A dose
      adjustment (mostly a dose reduction) was required in about half of the neonates
      in the first 2 weeks of life. As Mathai et al. carried out no neuropsychological
      tests, we do not know if their approach has a more beneficial effect on
      neurocognitive outcomes than other treatment strategies. Nevertheless, as
      tailoring the levothyroxine dose to severity rapidly normalized serum free T(4)
      levels, one would predict a beneficial effect of this approach on neurocognitive
      outcome.

PMID- 18825140
TI  - Determining the survival benefit of adjuvant radiotherapy in patients with node
      positive head and neck cancer.
AB  - Whether postoperative radiotherapy improves survival compared with surgery alone
      in patients with head and neck cancer remains unclear. This Practice Point
      commentary discusses the findings of a study by Kao et al. who used the
      Surveillance, Epidemiology, and End Results database to look for evidence of
      improved overall survival in patients with node-positive head and neck cancer.
      The analysis included 5,297 eligible patients who were treated with first-line
      surgery, of whom 4,307 (81%) received adjuvant radiotherapy. On multivariate
      analysis, adjuvant radiotherapy, age, primary tumor site, tumor and nodal stage
      were significant predictors of overall survival. While these results show an
      association between the use of adjuvant radiotherapy and improved overall
      survival in a selected group of patients, several aspects of the study limit its
      interpretation. Whether there is a causal relationship between postoperative
      radiotherapy and the observed overall survival benefit remains undetermined.

PMID- 18825141
TI  - Precancerous lesions of the breast.
AB  - The management of precancerous lesions of the breast has become a considerable
      clinical problem in the past 20 years, mostly as a consequence of increased
      detection due to the introduction of mammographic screening. It is not possible
      to identify with absolute certainty which of these lesions will progress to
      invasive carcinoma, and tailoring the treatment according to each individual case
      remains a challenge. There is a particular dilemma for surgeons, who must balance
      the risk of resecting too much and causing unnecessary cosmetic damage, or
      resecting too little and leaving an increased risk of recurrence. Further
      knowledge in the field of predictive and prognostic factors together with the
      development of gene-profiling techniques will, hopefully, provide answers to
      these questions. Among precancerous lesions of the breast, particular attention
      should be paid to ductal carcinoma in situ or intraductal carcinoma, appropriate
      treatment of which is crucial to prevent invasive breast cancer. Nearly all
      possible combinations of surgery, radiotherapy and medical treatments (anti
      estrogens) have been tested in different clinical trials, but the situation is
      far from satisfactory. We believe that an important contribution can come from
      oncoplastic surgery, which is the application of plastic and reconstructive
      surgical techniques to ensure both radical excision of the disease and acceptable
      cosmetic outcomes.

PMID- 18825142
TI  - Drug Insight: cetuximab in the treatment of recurrent and metastatic squamous
      cell carcinoma of the head and neck.
AB  - Patients with recurrent and/or metastatic squamous cell carcinoma of the head and
      neck (SCCHN) have a poor prognosis, particularly those whose disease has
      progressed on previous platinum-containing therapy. The epidermal growth factor
      receptor (EGFR) is expressed at very high levels in SCCHN and is associated with
      a poor prognosis. Several phase II-III studies have shown that the EGFR-targeting
      monoclonal antibody, cetuximab, offers clinical benefit for patients with SCCHN.
      Cetuximab monotherapy is active in patients whose cancer progresses on platinum
      containing therapy. Tumor response and patient survival are in excess of what is
      achieved with commonly used therapies in this setting. Addition of a platinum
      regimen to cetuximab in patients with disease that progresses on platinum seems
      to confer no further benefit over cetuximab alone, either in terms of response
      rate or survival. In the first-line setting, cetuximab plus platinum and 5
      fluorouracil significantly prolongs overall survival compared with platinum and 5
      fluorouracil alone. The superior survival observed with cetuximab compared with
      platinum-based treatment demonstrates that cetuximab is the most active treatment
      for recurrent and/or metastatic SCCHN, and is of particular clinical
      significance.

PMID- 18825143
TI  - Technology Insight: Combined external-beam radiation therapy and brachytherapy in
      the management of prostate cancer.
AB  - External-beam radiation therapy (EBRT) combined with brachytherapy is an
      attractive treatment option for selected patients with clinically localized
      prostate cancer. This therapeutic strategy offers dosimetric coverage if local
      regional microscopic disease is present and provides a highly conformal boost of
      radiation to the prostate and immediate surrounding tissues. Either low-dose-rate
      (LDR) permanent brachytherapy or high-dose-rate (HDR) temporary brachytherapy can
      be combined with EBRT; such combined-modality therapy (CMT) is typically used to
      treat patients with intermediate-risk to high-risk, clinically localized disease.
      Controversy persists with regard to indications for CMT, choice of LDR or HDR
      boost, isotope selection for LDR, and integration of EBRT and brachytherapy.
      Initial findings from prospective, multicenter trials of CMT support the
      feasibility of this strategy. Updated results from these trials as well as those
      of ongoing and new phase III trials should help to define the role of CMT in the
      management of prostate cancer. In the meantime, long-term expectations for
      outcomes of CMT are based largely on the experience of single institutions, which
      demonstrate that CMT with EBRT and either LDR or HDR brachytherapy can provide
      freedom from disease recurrence with acceptable toxicity.

PMID- 18825144
TI  - What role do antibiotics have in the treatment of IBD?

PMID- 18825145
TI  - Complementary and alternative medicine for IBS in adults: mind-body
      interventions.
AB  - Standard treatment for IBS focuses on the management or alleviation of the
      predominant gastrointestinal presenting symptoms, such as diarrhea or
      constipation, often using pharmacological therapy. For many patients, this
      approach is unsatisfactory, and patients frequently seek the advice of
      complementary and alternative medicine (CAM) practitioners in order to explore
      other treatment options. CAM practices include a broad range of modalities, and
      mind-body interventions hold particular promise as treatment modalities for IBS
      because psychological factors could have an important role in IBS symptomatology
      and quality of life. Psychological stressors are postulated to result in
      gastrointestinal symptoms through alteration of intestinal function mediated by
      the autonomic nervous system, hypothalamic-pituitary-adrenal axis and immune
      system. Hypnotherapy has the strongest supportive evidence as a beneficial mind
      body intervention for IBS. Clinical studies of hypnotherapy have uniformly shown
      improvement of gastrointestinal symptoms, anxiety, depression and quality of life
      in patients with IBS. Mindfulness meditation remains unstudied for IBS, but is
      theoretically attractive as a stress-reduction technique. There is a suggestion
      that relaxation therapy or multimodal therapy (a combination of relaxation
      therapy, education and psychotherapy) is beneficial for IBS. The most generally
      accepted psychological mind-body intervention is cognitive behavioral therapy,
      and clinical trials support the beneficial effects of cognitive behavioral
      therapy in patients with IBS.

PMID- 18825146
TI  - The Boston Acute Stroke Imaging Scale: ready for use in clinical practice?
AB  - This Practice Point commentary discusses a report by Torres-Mozqueda et al. on a
      newly developed classification instrument for predicting outcome after stroke,
      the Boston Acute Stroke Imaging Scale (BASIS). This tool incorporates imaging
      data on the patency of the vasculature and the parenchyma and classifies ischemic
      strokes as major (if large vessels are occluded or parenchymal changes are
      present) or minor (all others). When testing the scale, the authors looked at
      short-term outcome at the time of hospital discharge; patients classified with
      major stroke by BASIS had a higher mortality and longer hospital stay and were
      more likely to be discharged to a rehabilitation facility than patients with
      minor stroke. The authors concluded that BASIS can predict outcome after stroke.
      We point to several shortcomings in the study methodology and argue that,
      although BASIS has potential as a prognostic tool, further studies are needed
      before it can be widely used.

PMID- 18825148
TI  - Necrotizing enterocolitis: finding infants at highest risk.

PMID- 18825147
TI  - Glial pathology in an animal model of depression: reversal of stress-induced
      cellular, metabolic and behavioral deficits by the glutamate-modulating drug
      riluzole.
AB  - Growing evidence indicates that glia pathology and amino-acid neurotransmitter
      system abnormalities contribute to the pathophysiology and possibly the
      pathogenesis of major depressive disorder. This study investigates changes in
      glial function occurring in the rat prefrontal cortex (PFC) after chronic
      unpredictable stress (CUS), a rodent model of depression. Furthermore, we
      analyzed the effects of riluzole, a Food and Drug Administration-approved drug
      for the treatment of amyotrophic laterosclerosis, known to modulate glutamate
      release and facilate glutamate uptake, on CUS-induced glial dysfunction and
      depressive-like behaviors. We provide the first experimental evidence that
      chronic stress impairs cortical glial function. Animals exposed to CUS and
      showing behavioral deficits in sucrose preference and active avoidance exhibited
      significant decreases in 13C-acetate metabolism reflecting glial cell metabolism,
      and glial fibrillary associated protein (GFAP) mRNA expression in the PFC. The
      cellular, metabolic and behavioral alterations induced by CUS were reversed
      and/or blocked by chronic treatment with the glutamate-modulating drug riluzole.
      The beneficial effects of riluzole on CUS-induced anhedonia and helplessness
      demonstrate the antidepressant action of riluzole in rodents. Riluzole treatment
      also reversed CUS-induced reductions in glial metabolism and GFAP mRNA
      expression. Our results are consistent with recent open-label clinical trials
      showing the drug's effect in mood and anxiety disorders. This study provides
      further validation of hypothesis that glial dysfunction and disrupted amino-acid
      neurotransmission contribute to the pathophysiology of depression and that
      modulation of glutamate metabolism, uptake and/or release represent viable
      targets for antidepressant drug development.

PMID- 18825149
TI  - Gestational diabetes insipidus and intrauterine fetal death of monochorionic
      twins.
AB  - Gestational diabetes insipidus (GDI) is a rare disorder. The onset is usually in
      the third trimester of pregnancy. We present a 24-year-old primigravida in her
      35th week of a monochorionic-diamniotic twin pregnancy. The patient presented
      with intrauterine death of both twins accompanied by HELLP syndrome,
      hypernatremia and hemoconcentration. Urine osmolality below that of the plasma
      suggested GDI. 1-deamino-8D-arginine vasopressin (dDAVP) treatment was started
      with a quick response. GDI is probably the result of excessive activity of
      placental vasopressinase. In cases of liver dysfunction, the clearance rate of
      vasopressinase decreases, explaining the association of GDI with acute fatty
      liver and HELLP syndrome. Alert to this diagnosis, its evaluation and treatment
      is important.

PMID- 18825150
TI  - Ritscher-Schinzel cranio-cerebello-cardiac syndrome.

PMID- 18825151
TI  - Improving the health care experiences of families given the prenatal diagnosis of
      Trisomy 18.

PMID- 18825153
TI  - HIV-related renal disease and the utility of empiric therapy: not everyone needs
      to be biopsied.

PMID- 18825154
TI  - Islet transplantation--the imperative need for continued clinical trials.

PMID- 18825155
TI  - Nontraditional risk factors for cardiovascular disease in patients with chronic
      kidney disease.
AB  - Patients with chronic kidney disease (CKD) have a reduced lifespan, and a
      substantial proportion of these individuals die from cardiovascular disease.
      Although a large percentage of patients with CKD have traditional cardiac risk
      factors such as diabetes, hypertension and abnormalities in cholesterol,
      interventions to address these factors--which have significantly decreased
      cardiovascular mortality in the general population--have not shown such benefit
      in the CKD population. In addition, the severity and extent of cardiovascular
      complications in patients with CKD is disproportionate to the number and severity
      of traditional risk factors. This realization has focused attention on
      nontraditional cardiac risk factors that are particularly relevant to patients
      with CKD, including decreased hemoglobin levels, microalbuminuria, increased
      inflammation and oxidative stress, and abnormalities in bone and mineral
      metabolism. However, large prospective trials in patients with advanced CKD or in
      those requiring chronic dialysis have not shown that normalization of these
      nontraditional risk factors improves survival. Moreover, the mechanisms by which
      these nontraditional risk factors contribute to cardiovascular disease are
      unknown. Therefore, although current treatment of patients with CKD includes
      management of traditional and nontraditional risk factors, the value of modifying
      some nontraditional risk factors remains unclear.

PMID- 18825156
TI  - Negative association between plasma levels of adiponectin and polychlorinated
      biphenyl 153 in obese women under non-energy-restrictive regime.
AB  - The aim of this study was to reveal whether accumulation of the persistent
      organic pollutants (POPs), especially polychlorinated biphenyl (2,2',4,4',5,5'
      hexachlorobiphenyl, PCB 153), affects plasma levels of adiponectin in obese
      patients. The study was designed as a longitudinal intervention trial with a
      control group, where 27 obese women (body mass index (BMI)>30 kg/m(2); age 21-74
      years) were studied before (OB) and after (OB-LCD) a 3-month low-calorie-diet
      intervention (LCD; 5 MJ daily). As the control group, 9 female volunteers without
      LCD intervention were used (C; BMI=19-25 kg/m(2); age 21-64 years). Plasma levels
      of PCB 153 were measured by high-resolution gas chromatography with electron
      capture detection; total adiponectin and insulin plasma levels were quantified by
      immunoassays; and adiponectin multimeric complexes were quantified by
      immunoblotting. Plasma levels of total adiponectin, high and medium molecular
      weight multimers significantly negatively correlated with plasma levels of PCB
      153 in OB, but not in C or in OB-LCD, whereas the LCD intervention lowered BMI by
      3.3+/-3.0 kg/m(2). Our results may suggest suppression of adiponectin by PCB 153
      in obese women under non-energy-restrictive regime, which may contribute to the
      known association of PCB 153 and other POPs with type 2 diabetes.

PMID- 18825157
TI  - Glycemic index, cholecystokinin, satiety and disinhibition: is there an
      unappreciated paradox for overweight women?
AB  - BACKGROUND: The clinical utility of a low glycemic index (LGI) diet for appetite
      and food intake control is controversial. Complicating the issue are
      psychological and behavioral influences related to eating. OBJECTIVE: The aim of
      this study was to investigate the satiety and glycemic response to high GI (HGI)
      and LGI meals in overweight restrained (R, n=12) and unrestrained (UR, n=10)
      women. DESIGN AND MEASUREMENTS: In a randomized crossover study, subjective
      satiety, cholecystokinin (CCK), glucose, insulin, triacylglyceride (TG) and free
      fatty acids (FFAs) were measured at defined intervals for 8 h after the
      participants consumed HGI or LGI test meals. Test meals were matched for energy,
      energy density, macronutrient content and available carbohydrate, but differed by
      carbohydrate source; refined grain versus whole grain, respectively. RESULTS: The
      HGI meal resulted in greater satiety overall, suppressing hunger, desire to eat
      and prospective consumption compared with the LGI (P<0.01) meal. Plasma CCK was
      significantly elevated after the HGI meal compared with the LGI meal (P<0.001).
      Plasma glucose, insulin and TG were higher and FFAs were lower after the HGI meal
      compared with the LGI meal (P<0001). Dietary restraint did not significantly
      influence CCK (P=0.14) or subjective satiety (P>0.4); however, an interaction of
      restraint and disinhibition on CCK was apparent. CCK was blunted in R
      participants with higher disinhibition scores than UR or R participants with
      lower disinhibition scores (P<0.05). CONCLUSIONS: A LGI diet may not be suitable
      for optimal satiety and appetite control in overweight women. The relationship
      between cognitive influences of eating and biobehavioral outcomes requires
      further investigation.

PMID- 18825158
TI  - Subscapularis motor point block for spastic shoulders in patients with cervical
      cord injury.
AB  - STUDY DESIGN: Case series. OBJECTIVE: The objective was to study the effect of
      phenol blocks to the motor points of the subscapularis muscle in patients with
      cervical cord injury (CCI). SETTING: Spinal cord injury units of a national
      hospital in Tokyo. METHODS: The participants were seven patients with traumatic
      CCI, mean age 55.8 years (SD4.0), whose injury level were at the fifth cervical
      level and the American Spinal Injury Association (ASIA) impairment scale was A in
      2, C in 1 and D in 4. They were at least 5 months post-acute injury, and
      complained of pain and limited range of motion (ROM) of their shoulder joint that
      were unresponsive to usual rehabilitative interventions and medications. Before
      and after the phenol block to the motor points of the subscapularis muscle, we
      compared passive and active ROM of the shoulder (flexion, abduction and external
      rotation), spasticity of the subscapularis as assessed with the modified Ashworth
      scale, pain as evaluated with a visual analog scale, and eating item of the
      Functional Independence Measure. RESULTS: There were significant improvements in
      passive ROM in flexion (23.7 degrees ), abduction (19.4 degrees ) and external
      rotation (16.8 degrees ; P<0.05). Visual analog scale for shoulder pain was
      reduced from 6.0 to 3.4 (P<0.05). The modified Ashworth scale for shoulder
      spasticity, however, did not significantly change. The eating Functional
      Independence Measure item score improved significantly (P<0.05). CONCLUSIONS:
      This study suggests that subscapularis motor point block for pain and limited ROM
      with spastic shoulder is a useful technique in patients with CCI.

PMID- 18825159
TI  - Vaccination with dendritic cells pulsed with homogenate protein of spinal cord
      promotes functional recovery from spinal cord injury in mice.
AB  - STUDY DESIGN: Randomized, double-blinded animal experiment for neural functional
      recovery from spinal cord injury (SCI) through vaccination with immature
      dendritic cells (DCs) pulsed with homogenate protein of spinal cord (hpDCs) in
      mice. OBJECTIVE: To study the effect of hpDCs in the recovery from SCI in mice.
      METHOD: Immature DCs pulsed with homogenate protein of spinal cord, myelin basic
      protein (MBP) or phosphate-buffer solution (PBS) were injected into spinal cord
      injured mice locally or peritoneally. The functional recovery of spinal cord
      (open-field locomotor rating scale of Basso, Beattie and Bresnahan, BBB score)
      was measured weekly. The areas of injured region and cyst as well as the
      thickness of the glial scar were measured and the expressions of glial fibrillary
      acidic protein, neurofilament and nestin were detected to confirm the BBB scores.
      RESULTS: Eighty-four days after injection, the BBB score of the hpDCs group
      (peritoneally injected mice) reached 18.2+/-1.1, significantly higher than that
      the scores of the mbpDCs and control groups (16.3+/-2.1 and 10.0+/-2.0,
      respectively). The areas of injured region and cyst as well as the thickness of
      the glial scar of the hpDCs group were less than that of the control group.
      Meanwhile, the expression of nestin lasts up to 56 days after injection in the
      hpDCs group, while it disappeared in the mbpDCs and PBS groups. CONCLUSION:
      Implanting DCs pulsed with homogenate protein of spinal cord, but not mbpDCs or
      PBS alone, locally or peritoneally, have a significant effect on functional
      recovery and neural preservation from SCI.

PMID- 18825160
TI  - Systematic review of the effects of exercise therapy on the upper extremity of
      patients with spinal-cord injury.
AB  - OBJECTIVE: To assess the effects of exercise therapy (ET) on motor control and
      functional ability of the upper extremity in patients with cervical spinal cord
      injury (SCI). METHODS: An extensive systematic literature search in five
      databases was performed to identify clinical and (randomized) controlled trials,
      evaluating the effects of ET on motor control and functional ability in patients
      with SCI. The methodological quality of the selected studies was systematically
      assessed by three reviewers. RESULTS: Eight studies were included. Seven had good
      to-fair methodological quality, six reported positive effects of ET on motor
      control (for example, muscle strength or muscle grade) and four also reported
      positive effects on functional ability. Five of these studies focused on patients
      with long-lasting SCI. A great variety of therapeutic approaches were applied,
      even within ET there was a wide range of training characteristics. CONCLUSION:
      Although ET is a cornerstone in the treatment of the upper extremity in patients
      with SCI, only a small number of studies were included in the present review.
      Most of the included studies reported a positive effect of ET on upper extremity
      motor control and functional ability in SCI patients. As ET is effective in
      patients with SCI in the chronic stage, this might have implications for the
      follow up and further treatment of these patients. Future studies should be more
      specific in describing the characteristics of ET to verify that the ET is in
      accordance with the current standards for training and motor relearning.

PMID- 18825161
TI  - Getting a GRASP on CASP: properties and role of the cytohesin-associated
      scaffolding protein in immunity.
AB  - Cytohesin-associated scaffolding protein (CASP) is a novel human adaptor protein
      that participates in the assembly and recruitment of protein complexes associated
      with intracellular trafficking and signaling. Owing to its exclusive expression
      in cells of hematopoietic origin, CASP has attracted attention from many groups
      of researchers as a potential key contributor to molecular mechanisms governing
      cells of the immune system. The functional characterization of CASP has involved
      a wide range of experimental approaches and provided broad and interesting
      insights that, collectively, distinguish CASP as an important contributor for a
      fully functioning and rapidly responsive immune system. Protein interaction
      studies have demonstrated that CASP interacts with members of the ADP
      ribosylation factor (ARF)-activating cytohesin family and with a unique PDZ
      domain-containing member of the sorting nexin family of endocytic trafficking
      proteins. Physiological knockout studies, however, have revealed that CASP may
      not be an essential protein in immunity under normal conditions, but rather a
      streamlining protein that greatly ameliorates the efficiency of the immune system
      under circumstances of significant stress. Interestingly, an evolutionarily
      related neuronal protein, called GRP1-associated scaffolding protein, may further
      participate in CASP-related functions in immune cells, conferring a level of
      redundancy in associated molecular pathways. In this review, we summarize and
      critically review the current literature, bringing together common themes from a
      variety of studies that, when considered together, provide new insights into the
      nature and significance of CASP function in the broad context of immunity.

PMID- 18825163
TI  - Insulin and free oestradiol are independent risk factors for benign prostatic
      hyperplasia.
AB  - The aetiology of benign prostatic hyperplasia (BPH) remains unclear. The
      objective of the present study was to test the insulin, oestradiol and metabolic
      syndrome hypotheses as promoters of BPH. The design was a risk factor analysis of
      BPH in which the total prostate gland volume was related to endocrine and
      anthropometric factors. The participants studied were 184 representative men,
      aged 72-76 years, residing in Goteborg, Sweden. Using a multivariate analysis,
      BPH as measured by the total prostate gland volume correlated statistically
      significantly with fasting serum insulin (beta=0.200, P=0.028), free oestradiol
      (beta=0.233, P=0.008) and lean body mass (beta=0.257, P=0.034). Insulin and free
      oestradiol appear to be independent risk factors for BPH, confirming both the
      insulin and the oestradiol hypotheses. Our findings also seem to confirm the
      metabolic syndrome hypothesis. The metabolic syndrome and its major endocrine
      aberration, hyperinsulinaemia, are possible primary events in BPH.

PMID- 18825162
TI  - Prediction of CYP3A4 enzyme activity using haplotype tag SNPs in African
      Americans.
AB  - The CYP3A locus encodes hepatic enzymes that metabolize many clinically used
      drugs. However, there is marked interindividual variability in enzyme expression
      and clearance of drugs metabolized by these enzymes. We utilized comparative
      genomics and computational prediction of transcriptional factor binding sites to
      evaluate regions within CYP3A that were most likely to contribute to this
      variation. We then used a haplotype tagging single-nucleotide polymorphisms
      (htSNPs) approach to evaluate the entire locus with the fewest number of
      maximally informative SNPs. We investigated the association between these htSNPs
      and in vivo CYP3A enzyme activity using a single-point IV midazolam clearance
      assay. We found associations between the midazolam phenotype and age, diagnosis
      of hypertension and one htSNP (141689) located upstream of CYP3A4. 141689 lies
      near the xenobiotic responsive enhancer module (XREM) regulatory region of
      CYP3A4. Cell-based studies show increased transcriptional activation with the
      minor allele at 141689, in agreement with the in vivo association study findings.
      This study marks the first systematic evaluation of coding and noncoding
      variation that may contribute to CYP3A phenotypic variability.

PMID- 18825164
TI  - The patients less than 50 years: is there a need to lower the PSA cutoff point?
AB  - The aim of this study was to study the incidence and possibility of prostate
      cancer detection in patients <50 years with prostate-specific antigen (PSA) <4 ng
      ml(-1). Between January 2006 and January 2008, 355 men were subjected to radical
      cystoprostatectomy for bladder cancer. Among 162 cases without pathological
      prostatic invasion, random selection of two groups with serum PSA <4 ng ml(-1)
      was carried out. According to the age, 56 pairs in group A (< or =50 years) and
      group B (>50 years) were selected randomly. The resected prostate glands of each
      group were examined pathologically for evidence of prostatic adenocarcinoma.
      Correlation of the age groups with pathological findings, PSA, digital rectal
      examination (DRE) and body mass index (BMI) was carried out. The mean age of the
      groups (A and B) was 46.17+/-4.3 and 58.42+/-4.4 years, respectively. Mean PSA
      was 1.9+/-1.6 ng ml(-1) in group A and 2+/-1.6 ng ml(-1) in group B. Prostatic
      adenocarcinoma was detected in 1.8 and 10.7% in groups A and B, respectively
      (P=0.051). High-grade prostatic intraepithelial neoplasia (PIN) was higher in
      group A than in group B, 11 cases versus 4 (P=0.079). DRE was not significantly
      associated with pathological findings in those groups of patients. BMI was
      directly correlated with PSA in patients of group A (mean: 27.8+/-4.4, CC: 0.5,
      P=0.015), but not with that of group B (mean: 27.5+/-4.8, CC: 0.16, P=0.239). A
      new PSA cut-off point for younger patients (<50 years) is warranted. Serum PSA 2
      ng ml(-1) is recommended as a cut-off point to screen and biopsy advice for
      nonsymptomatic patients <50 years. High-grade PIN was higher among the younger
      patients with low serum PSA, which indeed needs a meticulous follow-up.

PMID- 18825165
TI  - FXR: a metabolic regulator and cell protector.
AB  - Farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily of
      ligand-activated transcription factors. As a metabolic regulator, FXR plays key
      roles in bile acid, cholesterol, lipid, and glucose metabolism. Therefore, FXR is
      a potential drug target for a number of metabolic disorders, especially those
      related to the metabolic syndrome. More recently, our group and others have
      extended the functions of FXR to more than metabolic regulation, which include
      anti-bacterial growth in intestine, liver regeneration, and hepatocarcinogenesis.
      These new findings suggest that FXR has much broader roles than previously
      thought, and also highlight FXR as a drug target for multiple diseases. This
      review summarizes the basic information of FXR but focuses on its new functions.

PMID- 18825166
TI  - Fast and low power Michelson interferometer thermo-optical switch on SOI.
AB  - We designed and fabricated silicon-on-insulator based Michelson interferometer
      (MI) thermo-optical switches with deep etched trenches for heat-isolation. Switch
      power was reduced approximately 20% for the switch with deep etched trenches, and
      the MI saved approximately 50% power than that of the Mach-Zehnder
      interferometer. 10.6 mW switch power, approximately 42 micros switch time for the
      MI with deep trenches, 13.14 mW switch power and approximately 34 micros switch
      time for the MI without deep trenches were achieved.

PMID- 18825167
TI  - Light scattering from 2D arrays of monodispersed Ag-nanoparticles separated by
      tunable nano-gaps: spectral evolution and analytical analysis of plasmonic
      coupling.
AB  - Two dimensional arrays of monodispersed Ag-nanoparticles separated by different
      gaps with sub-10 nm precision are fabricated on anodic alumina substrates with
      self-organized pores. Light scattering spectra from the arrays evolve with the
      gaps, revealing plasmonic coupling among the nanoparticles, which can be
      satisfactorily interpreted by analytical formulae derived from generic dipolar
      approximation. The general formulism lays down a foundation for predicting the Q
      factor of an array of metallic nano-particles and its geometric characteristics.

PMID- 18825168
TI  - All-optical regenerative NRZ-to-RZ format conversion using coupled ring-resonator
      optical waveguide.
AB  - This paper proposes a scheme for format conversion from a distorted non-return-to
      zero (NRZ) signal to a high-quality return-to-zero (RZ) signal, using the
      nonlinearity in a coupled ring-resonator optical waveguide (CROW) on a silicon
      chip. In this method, a distorted NRZ signal is amplified and fed into the CROW
      together with an RZ pulse train. The CROW performs as a nonlinear step gate for
      the RZ pulse train, which outputs amplitude-equalized RZ pulses inheriting the
      information from the NRZ signal. Clearly, the integration of the format
      conversion and regeneration simplifies the system. Our simulations performed at
      10 Gb/s and 40 Gb/s verify the feasibility of our proposal.

PMID- 18825169
TI  - Photonic band-gap engineering in UV fiber gratings by the arc discharge
      technique.
AB  - Localized heat treatments combined with local non-adiabatic tapering is proposed
      as suitable tool for the engineering of photonic band-gaps in UV-written fiber
      Bragg gratings (FBGs). In particular, here, we propose the use of the electric
      arc discharge to achieve localized defects along the FBG structure, however
      differently from previously reported works, we demonstrate how this post
      processing tool properly modified can be exploited to achieve the full control of
      the spectral characteristics of the final device. Also, we show how the suitable
      choice of the grating features and the correct selection of the defect geometry
      can be efficiently used to achieve interesting features for both communication
      and sensing applications.

PMID- 18825170
TI  - Three-dimensional characterization of extreme ultraviolet mask blank defects by
      interference contrast photoemission electron microscopy.
AB  - A photoemission electron microscope based on a new contrast mechanism
      "interference contrast" is applied to characterize extreme ultraviolet
      lithography mask blank defects. Inspection results show that positioning of
      interference destructive condition (node of standing wave field) on surface of
      multilayer in the local region of a phase defect is necessary to obtain best
      visibility of the defect on mask blank. A comparative experiment reveals
      superiority of the interference contrast photoemission electron microscope
      (Extreme UV illumination) over a topographic contrast one (UV illumination with
      Hg discharge lamp) in detecting extreme ultraviolet mask blank phase defects. A
      depth-resolved detection of a mask blank defect, either by measuring anti-node
      peak shift in the EUV-PEEM image under varying inspection wavelength condition or
      by counting interference fringes with a fixed illumination wavelength, is
      discussed.

PMID- 18825171
TI  - Electronic dispersion compensation using full optical-field reconstruction in
      10Gbit/s OOK based systems.
AB  - We investigate the design of electronic dispersion compensation (EDC) using full
      optical-field reconstruction in 10Gbit/s on-off keyed transmission systems
      limited by optical signal-to-noise ratio (OSNR). By effectively suppressing the
      impairment due to low-frequency component amplification in phase reconstruction,
      properly designing the transmission system configuration to combat fiber
      nonlinearity, and successfully reducing the vulnerability to thermal noise, a
      4.8dB OSNR margin can be achieved for 2160km single-mode fiber transmission
      without any optical dispersion compensation. We also investigate the performance
      sensitivity of the scheme to various system parameters, and propose a novel
      method to greatly enhance the tolerance to differential phase misalignment of the
      asymmetric Mach-Zehnder interferometer. This numerical study provides important
      design guidelines which will enable full optical-field EDC to become a cost
      effective dispersion compensation solution for future transparent optical
      networks.

PMID- 18825172
TI  - Mitigation of spectral mis-registration effects in imaging spectrometers via
      cubic spline interpolation.
AB  - The effects of spectral curvature (smile) on the co-registration of measured
      radiance spectra were analyzed for a dispersive imaging spectrometer. The spectra
      measured by the imaging spectrometer with spectral curvature were re-sampled
      using cubic spline Interpolation to mitigate the mis-registration of spectral
      radiance measurement. After correction, the co-registration of measured radiance
      spectra is distinctly improved.

PMID- 18825173
TI  - Improvement of transmission properties through two-bend resonance by holographic
      design for a two-dimensional photonic crystal waveguide.
AB  - We have investigated the transmission properties of a photonic crystal waveguide
      (PCW) formed by holographic lithography for the first time with a two-dimensional
      (2D) triangular holographic photonic crystal (PhC) including a line defect with
      two 60 masculine bends. Calculations have shown that for this PCW high
      transmission (>90%) through sharp corners can be obtained in a wide frequency
      range from 0.298 to 0.310 (omega alpha/2pi c) with the relative band gap of 4%
      when the dielectric contrast is 7.6:1. As far as we know, this result should be
      the widest frequency range with high transmission (>90%) in the waveguide of
      similar 2D triangular PhCs ever reported. We have also found that the specific
      holographic designs of PhC have strong influence on the resonance between the two
      waveguide bends, and thus this fact can be used as an effective means to improve
      the transmission property of 2D holographic PCW. In addition to the simplicity
      and low cost of holographic fabrication of PhCs, these features may reveal the
      possibly better guiding ability of holographic PCW than the conventional
      waveguide and the promising potential of the former in the application of
      photonic integrated circuits.

PMID- 18825174
TI  - Excitonic polaritons in Fibonacci quasicrystals.
AB  - The fabrication and characterization of light-emitting one-dimensional photonic
      quasicrystals based on excitonic resonances is reported. The structures consist
      of high-quality GaAs/AlGaAs quantum wells grown by molecular-beam epitaxy with
      wavelength-scale spacings satisfying a Fibonacci sequence. The polaritonic
      (resonant light-matter coupling) effects and light emission originate from the
      quantum well excitonic resonances. Measured reflectivity spectra as a function of
      detuning between emission and Bragg wavelength are in good agreement with
      excitonic polariton theory. Photoluminescence experiments show that active
      photonic quasicrystals, unlike photonic crystals, can be good light emitters:
      While their long-range order results in a stopband similar to that of photonic
      crystals, the lack of periodicity results in strong emission.

PMID- 18825175
TI  - Transformations of continuously self-focusing and continuously self-defocusing
      dissipative solitons.
AB  - Dissipative media admit the existence of two types of stationary self-organized
      beams: continuously self-focused and continuously self- defocused. Each beam is
      stable inside of a certain region of its existence. Beyond these two regions,
      beams loose their stability, and new dynamical behaviors appear. We present
      several types of instabilities related to each beam configuration and give
      examples of beam dynamics in the areas adjacent to the two regions. We observed
      that, in one case beams loose the radial symmetry while in the other one the
      radial symmetry is conserved during complicated beam transformations.

PMID- 18825176
TI  - Multi-level diffractive optics for single laser exposure fabrication of telecom
      band diamond-like 3-dimensional photonic crystals.
AB  - We present a novel multi-level diffractive optical element for diffractive optic
      near-field lithography based fabrication of large-area diamond-like photonic
      crystal structure in a single laser exposure step. A multi-level single-surface
      phase element was laser fabricated on a thin polymer film by two-photon
      polymerization. A quarter-period phase shift was designed into the phase elements
      to generate a 3D periodic intensity distribution of double basis diamond-like
      structure. Finite difference time domain calculation of near-field diffraction
      patterns and associated isointensity surfaces are corroborated by definitive
      demonstration of a diamond-like woodpile structure formed inside thick
      photoresist. A large number of layers provided a strong stopband in the telecom
      band that matched predictions of numerical band calculation. SEM and spectral
      observations indicate good structural uniformity over large exposure area that
      promises 3D photonic crystal devices with high optical quality for a wide range
      of motif shapes and symmetries. Optical sensing is demonstrated by spectral
      shifts of the Gamma-Zeta stopband under liquid emersion.

PMID- 18825177
TI  - Double phase conjugate mirror using Sn2P2S6 for injection locking of a laser
      diode bar.
AB  - We demonstrate double phase-conjugation in pure and Te-doped Sn(2)P(2)S(6), a
      semiconducting ferroelectric material, at the wavelength of 685 nm. We observe a
      phase conjugate reflectivity of more than 800% at an intensity ratio of the pump
      beams of 44 for Te-doped Sn(2)P(2)S(6). Using a laser diode bar emitting at 685
      nm, we demonstrate double phase conjugation of three independent emitters of the
      laser diode bar with a single mode master laser. By adjusting the center
      wavelength of the master laser to the center wavelength of an emitter with an
      accuracy of less than 0.1 nm, locking of any emitter of the laser diode bar is
      demonstrated. We improve the spectral width of the emitter from 0.5 nm to below
      2.5 x 10(-4) nm.

PMID- 18825178
TI  - In-fiber microchannel device filled with a carbon nanotube dispersion for passive
      mode-lock lasing.
AB  - Fueled by their high third-order nonlinearity and nonlinear saturable absorption,
      carbon nanotubes (CNT) are expected to become an integral part of next-generation
      photonic devices such as all-optical switches and passive mode-locked lasers.
      However, in order to fulfill this expectation it is necessary to identify a
      suitable platform that allows the efficient use of the optical properties of CNT.
      In this paper, we propose and implement a novel device consisting of an
      optofluidic device filled with a dispersion of CNT. By fabricating a microchannel
      through the core of a conventional fiber and filling it with a homogeneous
      solution of CNTs on Dimethylformamide (DMF), a compact, all-fiber saturable
      absorber is realized. The fabrication of the micro-fluidic channel is a two-step
      process that involves femtosecond laser micro-fabrication and chemical etching of
      the laser-modified regions. All-fiber high-energy, passive mode-locked lasing is
      demonstrated with an output power of 13.5 dBm. The key characteristics of the
      device are compactness and robustness against optical, mechanical and thermal
      damage.

PMID- 18825179
TI  - Total absorption of light by lamellar metallic gratings.
AB  - Lamellar gratings illuminated in conical (off-plane) mounting can achieve with
      suitable optogeometrical parameters (grating profile, angle of incidence and
      wavelength) a total absorption of light for any polarization provided there is
      only the zeroth propagating order. A detailed analysis shows that electromagnetic
      resonances are involved and their nature strongly depends on the polarization.
      When the incident electric field is parallel to the cross-section of the grating,
      the resonance is provoked by the excitation of surface plasmons. For the
      orthogonal polarization, total absorption occurs for deep gratings only, when the
      grooves behave like resonant optical cavities. It is possible to reduce the
      optimal grating height by filling the grooves with a high refractive index
      material.

PMID- 18825180
TI  - All-angle negative refraction and imaging in a bulk medium made of metallic
      nanowires in the visible region.
AB  - We theoretically demonstrated that all-angle negative refraction and imaging can
      be implemented by metallic nanowires embedded in a dielectric matrix. When the
      separation between the nanowires is much smaller than the incident wavelength,
      these structures can be characterized as indefinite media, whose effective
      permittivities perpendicular and parallel to the wires are opposite in signs.
      Under this condition, the dispersion diagram is hyperbolic for transverse
      magnetic waves propagating in the nanowire system, thereby exhibiting all-angle
      negative refraction. Such indefinite media can operate over a broad frequency
      range (visible to near-infrared) far from any resonances, thus they offer an
      effective way to manipulate light propagation in bulk media with low losses,
      allowing potential applications in photonic devices.

PMID- 18825181
TI  - Approximation approach of designing practical cloaks with arbitrary shapes.
AB  - The approach of designing cloaks with arbitrary shapes was investigated. The
      coordinate transformation was considered as a homeomorphous topological mapping
      and the related geometrical description was proposed by introducing position
      surfaces and tracing lines. Then an approximation approach was presented, which
      considers a close shape as a polyhedron and performs the spatial compression in a
      general method. As an example of this approach, we deduced the material parameter
      equations for two-dimensional polygon cloaks and confirmed the results through
      numerical simulations. Our approach opens up possibilities of designing practical
      cloaks with arbitrary shapes through numerical or/and semi-analytical methods.

PMID- 18825182
TI  - Transmission and reflection of electromagnetically induced absorption grating in
      homogeneous atomic media.
AB  - We theoretically study the transmission and reflection of the probe travelling
      wave in an electromagnetically induced absorption grating (EIG), which is created
      in a three-level Lambda-type atomic system when the coupling field is a standing
      wave. Using the system, we show that a photonic stop band can exist on one side
      away from the resonance point in ultracold atomic gas, while there is an enhanced
      absorption at resonance and small reflection around it in the thermal atomic gas.
      Because our method can deal with such two cases, it is helpful to further
      understand the effects of the Doppler effect on atomic coherence and
      interference.

PMID- 18825183
TI  - Steep atomic dispersion induced by velocity-selective optical pumping.
AB  - We demonstrate a method of preparation of broadband sign-reversible dispersion in
      alkali vapour based on velocity-selective optical pumping. The refractive index
      in Rb vapour has been measured using a heterodyne method. The magnitudes of the
      normal and anomalous dispersion, which are almost constant over a spectral region
      of approximately 40 MHz, can lead to a reduced (V(g) approximately c/230) or
      negative (V(g) approximately -c/27) group velocity of light.

PMID- 18825184
TI  - Differential-phase-shift quantum secret sharing.
AB  - A quantum secret sharing (QSS) protocol based on a differential-phase-shift
      scheme is proposed, which quantum mechanically provides a full secret key to one
      party and partial keys to two other parties. A weak coherent pulse train is
      utilized instead of individual photons as in conventional schemes. Compared with
      previous QSS protocols, the present one features a simple setup, is suitable for
      fiber transmission, and offers the possibility for a high key creation rate. An
      experiment is also carried out to demonstrate the operation.

PMID- 18825185
TI  - Experimental investigation of SPM in long-haul direct-detection OFDM systems.
AB  - We experimentally investigate the effect of self-phase modulation on direct
      detection orthogonal frequency division multiplexed (OFDM) transmission at 11.1
      Gb/s over 960km and 1600km uncompensated standard single-mode fiber links. We
      show that for long-haul systems, the penalties due to nonlinear distortion in
      OFDM systems are comparable to those in links employing electronic predistortion.

PMID- 18825186
TI  - Non-radially polarized THz pulse emitted from femtosecond laser filament in air.
AB  - Femtosecond laser filament could produce THz wave in forward direction. In our
      experiment, THz pulse emitted from a femtosecond laser filament has been
      investigated. It was found that the polarization of the studied THz pulse mainly
      appears as elliptical. This observation supplements the previous conclusion
      obtained by C. D'Amico et al. that THz wave emitted by a filament is radially
      polarized. The mechanism of generating elliptically polarized THz wave has been
      interpreted by either four-wave optical rectification or second order optical
      rectification inside the filament zone where centro-symmetry of the air is broken
      by the femtosecond laser pulse.

PMID- 18825187
TI  - Top-emitting white organic light-emitting devices with down-conversion phosphors:
      theory and experiment.
AB  - White top-emitting organic light-emitting devices (TEOLEDs) with down-conversion
      phosphors are investigated from theory and experiment. The theoretical simulation
      was described by combining the microcavity model with the down-conversion model.
      A White TEOLED by the combination of a blue TEOLED with organic down-conversion
      phosphor 3-(4-(diphenylamino)phenyl)-1-pheny1prop-2-en-1-one was fabricated to
      validate the simulated results. It is shown that this approach permits the
      generation of white light in TEOLEDs. The efficiency of the white TEOLED is twice
      over the corresponding blue TEOLED. The feasible methods to improve the
      performance of such white TEOLEDs are discussed.

PMID- 18825188
TI  - Optics system design applying a micro-prism array of a single lens stereo image
      pair.
AB  - In this study we apply a micro-prism array technique to enable a single lens CCD
      to capture a stereo image for the simulation of double lens vision. A micro-prism
      array plate serves as the basis for design, which also improves the lightweight
      and portability of the overall system in addition to lowering the mass-production
      costs. Most important of all, this design possesses the characteristics of
      integration compatibility between general-purpose and video camera.

PMID- 18825189
TI  - Strong influence of nonlinearity and surface plasmon excitations on the lateral
      shift.
AB  - When surface plasmons are excited at a metal-dielectric interface, the
      electromagnetic field takes a very large value near the interface. If the
      dielectric is a nonlinear Kerr medium, then the effect of nonlinearity can be
      greatly amplified due to the field enhancement. In this paper, we calculate the
      lateral shift of p wave beams incident on metal-dielectric multilayer systems in
      the Otto configuration in a numerically exact manner, using the invariant
      imbedding method of wave propagation in nonlinear stratified media. In the linear
      case, we find that the lateral shift becomes very large at the incident angles
      where the surface plasmons are excited. As the nonlinearity is turned on, the
      value of the lateral shift changes rapidly. We find that even a small change of
      the intensity of the incident wave can cause a huge change of the lateral shift.
      We propose that this phenomenon can be applied to designing precise optical
      switches operating at small powers.

PMID- 18825190
TI  - Investigation of diffuse correlation spectroscopy in multi-layered media
      including the human head.
AB  - In this work, diffuse correlation spectroscopy (DCS) is explored in multi-layered
      geometries. A quantitative comparison of an homogeneous versus a two-layered
      model efficiencies to recover flow changes is presented. By simulating a
      realistic human head with MRI anatomical data, we show that the two-layered model
      allows distinction between changes in superficial layers and brain. We also show
      that the two-layered model provides a better estimate of the flow change than the
      homogeneous one. Experimental measurements with a two-layered dynamical phantom
      confirm the ability of the two-layered analytical model to distinguish flow
      increase in each layer.

PMID- 18825191
TI  - Dichroic rugate filters based on birefringent porous silicon.
AB  - Rugate filters made of anisotropically nanostructured birefringent silicon have
      been fabricated and studied by polarization-resolved transmission measurements.
      Electrochemical etching of a (110) oriented Si wafer results in porous silicon
      layers which exhibit a strong in-plane birefringence. We demonstrate that a
      sinusoidal refractive index variation of birefringent porous silicon combined
      with index-matching layers and apodization results in a dichroic rugate filter
      having a stop-band dependent on the polarization direction of the incident light
      without higher-order harmonics and sidelobes. We also demonstrate that the
      combination of different dichroic rugate filters allow us to realize filters with
      more complex properties in a single preparation step.

PMID- 18825192
TI  - Efficient Yb laser fibers with low photodarkening by optimization of the core
      composition.
AB  - We report on photodarkening (PD) investigations at Yb doped fibers with specific
      variation of the concentrations of the codopants aluminum and phosphorus,
      measured during cladding pumping at 915 nm. A core composition with equal content
      of Al and P is most promising to achieve Yb fibers with low PD, high laser
      efficiency and low numerical aperture of the laser core despite of high codoping.
      A laser output power of more than 100 W was demonstrated on such a fiber with a
      slope efficiency of 72%. The correlation of the PD loss with the NIR-excited
      cooperative luminescence encourages the supposition that cooperative energy
      transfer from excited Yb(3+) ions to the atomic defect precursors in the core
      glass enables the formation of color centers in the pump-induced PD process.

PMID- 18825193
TI  - Compact plasmonic variable optical attenuator.
AB  - We demonstrate plasmonic nanowire-based thermo-optic variable optical attenuators
      operating in the 1525-1625 nm wavelength range. The devices have a footprint as
      low as 1 mm, extinction ratio exceeding 40 dB, driving voltage below 3 V, and
      full modulation bandwidth of 1 kHz. The polarization dependent loss is shown to
      be critically dependent on the nanowire geometry but devices with polarization
      dependent loss as low as +/-2.5 dB PDL over most of the attenuation range have
      been fabricated. We propose an even more compact device design to reduce
      insertion loss to approximately 1 dB.

PMID- 18825194
TI  - Fainter and closer: finding planets by symmetry breaking.
AB  - Imaging of planets is very difficult, due to the glare from their nearby, much
      brighter suns. Static and slowly-evolving aberrations are the limiting factors,
      even after application of adaptive optics. The residual speckle pattern is highly
      symmetrical due to diffraction from the telescope's aperture. We suggest to break
      this symmetry and thus to locate planets hidden beneath it. An eccentric pupil
      mask is rotated to modulate the residual light pattern not removed by other
      means. This modulation is then exploited to reveal the planet's constant signal.
      In well-corrected ground-based observations we can reach planets six stellar
      magnitudes fainter than their sun, and only 2-3 times the diffraction limit from
      it. At ten times the diffraction limit, we detect planets 16 magnitudes fainter.
      The stellar background drops by five magnitudes.

PMID- 18825195
TI  - Beam propagation factor of partially coherent flat-topped beams in a turbulent
      atmosphere.
AB  - The Wigner distribution function (WDF) has been used to study the beam
      propagation factor (M(2)-factor) for partially coherent flat-topped (PCFT) beams
      with circular symmetry in a turbulent atmosphere. Based on the extended Huygens
      Fresnel principle and the definition of the WDF, an expression for the WDF of
      PCFT beams in turbulence has been given. By use of the second-order moments of
      the WDF, the analytical formulas for the root-mean-square (rms) spatial width,
      the rms angular width, and the M(2)-factor of PCFT beams in turbulence have been
      derived, which can be applied to cases of different spatial power spectra of the
      refractive index fluctuations. The rms angular width and the M(2)-factor of PCFT
      beams in turbulence have been discussed with numerical examples. It can be shown
      that the M(2)-factor of PCFT beams in turbulence depends on the beam order,
      degree of global coherence of the source, waist width, wavelength, spatial power
      spectrum of the refractive index fluctuations, and propagation distance.

PMID- 18825196
TI  - Elongation of surface plasmon polariton propagation length without gain.
AB  - We have demonstrated that an addition of highly concentrated rhodamine 6G
      chloride dye to the PMMA film adjacent to a silver film can cause 30% elongation
      of the propagation length of surface Plasmon polaritons (SPPs). The possibility
      to elongate the SPP propagation length without optical gain opens a new
      technological dimension to low-loss nanoplasmonic and metamaterials.

PMID- 18825197
TI  - Broadband high-channel-count phase-only sampled fiber Bragg gratings based on
      spectral Talbot effect.
AB  - A novel method of generating broadband high-count-channel optical filters in
      phase-only sampled fiber Bragg grating based on spectral Talbot effect is
      presented. Integer and/or fractional Talbot effects are examined using both
      Dammann and multi-level discrete phase-only sampling function. It is found that
      very high-count channels in a wide spectral band that covers the whole C band can
      be obtained with very limited number of discrete phase transitions in each
      sampling period. It provides a novel method for making high-channel-count FBG
      filters that is otherwise difficult or impossible using conventional discrete
      phase-only sampled FBGs.

PMID- 18825198
TI  - The application of Fresnel zone plate based projection in optofluidic microscopy.
AB  - Optofluidic microscopy (OFM) is a novel technique for low-cost, high-resolution
      on-chip microscopy imaging. In this paper we report the use of the Fresnel zone
      plate (FZP) based projection in OFM as a cost-effective and compact means for
      projecting the transmission through an OFM's aperture array onto a sensor grid.
      We demonstrate this approach by employing a FZP (diameter = 255 microm, focal
      length = 800 microm) that has been patterned onto a glass slide to project the
      transmission from an array of apertures (diameter = 1 microm, separation = 10
      microm) onto a CMOS sensor. We are able to resolve the contributions from 44
      apertures on the sensor under the illumination from a HeNe laser (wavelength =
      633 nm). The imaging quality of the FZP determines the effective field-of-view
      (related to the number of resolvable transmissions from apertures) but not the
      image resolution of such an OFM system--a key distinction from conventional
      microscope systems. We demonstrate the capability of the integrated system by
      flowing the protist Euglena gracilis across the aperture array microfluidically
      and performing OFM imaging of the samples.

PMID- 18825199
TI  - Reversed dispersion slope photonic bandgap fibers for broadband dispersion
      control in femtosecond fiber lasers.
AB  - Higher-order-mode solid and hollow core photonic bandgap fibers exhibiting
      reversed or zero dispersion slope over tens or hundreds of nanometer bandwidths
      within the bandgap are presented. This attractive feature makes them well suited
      for broadband dispersion control in femtosecond pulse fiber lasers, amplifiers
      and optical parametric oscillators. The canonical form of the dispersion profile
      in photonic bandgap fibers is modified by a partial reflector layer/interface
      placed around the core forming a 2D cylindrical Gires-Tournois type
      interferometer. This small perturbation in the index profile induces a frequency
      dependent electric field distribution of the preferred propagating higher-order
      mode resulting in a zero or reversed dispersion slope.

PMID- 18825200
TI  - Zero-broadening and pulse compression slow light in an optical fiber at high
      pulse delays.
AB  - We show in theory and experiment that in a SBS based delay line pulses can be
      delayed to more than a bit period without broadening. Zero-broadening is possible
      since the broadening due to the narrow Brillouin gain bandwidth can be
      compensated by the group velocity dispersion accompanied with the pulse delay. We
      achieve compensation by a superposition of a broad gain with two narrow losses at
      its wings. In our experiments 1.9ns pulses were delayed to around 1.5Bit, at the
      same time its FWHM width was compressed to 80%. Therefore, besides slowing down
      pulses, the method could have the potential to compensate the fiber dispersion.

PMID- 18825201
TI  - Sensitivity calibration of digital colour cameras for auroral imaging.
AB  - A method to sensitivity calibrate Digital Single Lens Reflective (DSLR) cameras
      is outlined. A low intensity calibrated light source tunable in wavelength is
      described. 31 monochromatic lines from 4000 to 7000 A with a bandpass of
      approximately 12 A were used to find the spectral responses for the D70 and the
      D200 cameras manufactured by Nikon. The source radiance ranged from about 300 to
      1.6k R/A. The cameras were operated in manual mode with 4 seconds exposure time
      at ISO 1600, which are typical settings required for night time photography of
      the aurora. For the Nikon D200 camera, the blue, green and red spectral
      responsivities peak at 4600, 5300 and 5900 A, respectively. The response was high
      for the blue colour channel with a clear cut-off at 4100 A for the UV part of the
      spectrum. The red channel response indicates low sensitivity above 6600 A. The
      D70 shows similar spectral responsivity, except that it peaks in the green colour
      channel and it is more sensitive to both UV and NIR radiation. Both cameras are
      capable of detecting night- and dayside auroral at 4 second exposure time. For
      optimal auroral imaging capability, the green and red spectral responsivities
      need to be shifted up by about 300 and 400 A in wavelength.

PMID- 18825202
TI  - Study of surface relief gratings on azo organometallic films in picosecond
      regime.
AB  - Materials for optical data storage and optical information processing must
      exhibit good holographic properties. Many materials for these applications have
      been already proposed. Here we describe a grating inscription process
      characterized by short inscription time and long-time stability. A series of
      ruthenium-acetylide organometallic complexes containing an azobenzene fragment
      were synthesized. Photo-induced gratings were produced by short pulse (16 ps, 532
      nm) laser irradiation. The surface relief gratings formed at the same time were
      observed by atomic force microscope. In this work, we highlight the short
      inscription times brought into play as well as the good temporal stability of
      these gratings stored at room temperature. We study the influence of the
      polarization states and the light intensity of writing beams on the dynamics of
      the surface relief gratings formation and we compare these results with those of
      a known representative of azobenzene derivative (Disperse Red 1). Lastly, we show
      that it is possible to write two-dimensional surface relief gratings.

PMID- 18825203
TI  - An optimal permissible source region strategy for multispectral bioluminescence
      tomography.
AB  - Multispectral bioluminescence tomography (BLT) attracts increasing more attention
      in the area of small animal studies because multispectral data acquisition could
      help in the 3D location of bioluminescent sources. Generally, BLT problem is ill
      posed and a priori information is indispensable to reconstruction bioluminescent
      source uniquely and quantitatively. In this paper, we propose a spectrally solved
      bioluminescence tomography algorithm with an optimal permissible source region
      strategy. Being the most different from earlier studies, an optimal permissible
      source region strategy which is automatically selected without human intervention
      is developed to reduce the ill-posedness of BLT and therefore improves the
      reconstruction quality. Furthermore, both numerical stability and computational
      efficiency benefit from the strategy. In the numerical experiments, a
      heterogeneous phantom is used to evaluate the proposed algorithm and the
      synthetic data is produced by Monte Carlo method for avoiding the inverse crime.
      The results demonstrate the feasibility and potential of our methodology for
      reconstructing the distribution of bioluminescent sources.

PMID- 18825204
TI  - Aberration fields of a combination of plane symmetric systems.
AB  - By generalizing the wave aberration function to include plane symmetric systems,
      we describe the aberration fields for a combination of plane symmetric systems.
      The combined system aberration coefficients for the fields of spherical
      aberration, coma, astigmatism, defocus and distortion depend on the individual
      aberration coefficients and the orientations of the individual plane symmetric
      component systems. The aberration coefficients can be used to calculate the
      locations of the field nodes for the different types of aberration, including
      coma, astigmatism, defocus and distortion. This work provides an alternate view
      for combining aberrations in optical systems.

PMID- 18825205
TI  - On-chip silicon photonic wavelength control of optical fiber lasers.
AB  - Tunable silicon microring filters are used to demonstrate CMOS-compatible on-chip
      wavelength control of Er(+) doped fiber-lasers. An onchip Ni-Cr micro-heater
      consuming up to 20 mW is capable of tuning the Si microring filter by 1.3 nm with
      a lasing linewidths narrower than 0.02 nm. This approach enables arbitrary
      multiple wavelength generation on a silicon chip. Possible applications include
      on-chip and chip-to-chip dense-wavelength division multiplexed communications and
      sensor interrogation.

PMID- 18825206
TI  - Color-changing and color-tunable photonic bandgap fiber textiles.
AB  - We present the fabrication and use of plastic Photonic Band Gap Bragg fibers in
      photonic textiles for applications in interactive cloths, sensing fabrics,
      signage and art. In their cross section Bragg fibers feature periodic sequence of
      layers of two distinct plastics. Under ambient illumination the fibers appear
      colored due to optical interference in their microstructure. Importantly, no dyes
      or colorants are used in fabrication of such fibers, thus making the fibers
      resistant to color fading. Additionally, Bragg fibers guide light in the low
      refractive index core by photonic bandgap effect, while uniformly emitting a
      portion of guided color without the need of mechanical perturbations such as
      surface corrugation or microbending, thus making such fibers mechanically
      superior to the standard light emitting fibers. Intensity of side emission is
      controlled by varying the number of layers in a Bragg reflector. Under white
      light illumination, emitted color is very stable over time as it is defined by
      the fiber geometry rather than by spectral content of the light source. Moreover,
      Bragg fibers can be designed to reflect one color when side illuminated, and to
      emit another color while transmitting the light. By controlling the relative
      intensities of the ambient and guided light the overall fiber color can be
      varied, thus enabling passive color changing textiles. Additionally, by
      stretching a PBG Bragg fiber, its guided and reflected colors change
      proportionally to the amount of stretching, thus enabling visually interactive
      and sensing textiles responsive to the mechanical influence. Finally, we argue
      that plastic Bragg fibers offer economical solution demanded by textile
      applications.

PMID- 18825207
TI  - Generation of radially polarized beam with a segmented spiral varying retarder.
AB  - We convert a linearly polarized Gaussian beam into a radially polarized doughnut
      beam with an eight-segment spirally varying retarder (SVR) at wavelength of 808
      nm. The SVR is designed based on the linear birefringence of alpha-barium borate
      (alpha-BBO) crystal and fabricated using a dry etching process. Radially
      polarized light of high purity (> 96% at far-field distribution) was generated
      experimentally using the segmented SVR positioned between two quarter waveplates
      with orthogonal slow axes. The emergent polarization can be switched between
      radially and azimuthally polarized cylindrical vector beams with a pair of half
      wave plates.

PMID- 18825208
TI  - White light sources based on multiple precision selective micro-filling of
      structured optical waveguides.
AB  - Multiple precision selective micro-filling of a structured optical fibre using
      three luminescent dyes enables the simultaneous capture of red, blue and green
      luminescence within the core to generate white light. The technology opens up a
      new approach to integration and superposition of the properties of multiple
      materials to create unique composite properties within structured waveguides.

PMID- 18825209
TI  - Non-harmonic potential of a single beam optical trap.
AB  - Since the invention of optical traps based on a single laser beam, the potential
      experienced by a trapped specimen has been assumed harmonic, in the central part
      of the trap. It has remained unknown to what extent the harmonic region persists
      and what occurs beyond. By employing a new method, we have forced the trapped
      object to extreme positions, significantly further than previously achieved in a
      single laser beam, and thus experimentally explore an extended trapping
      potential. The potential stiffens considerably as the bead moves to extreme
      positions and therein is not well described by simple Uhlenbeck theories.

PMID- 18825210
TI  - Equalization-enhanced phase noise for coherent-detection systems using electronic
      digital signal processing.
AB  - In coherent optical systems employing electronic digital signal processing, the
      fiber chromatic dispersion can be gracefully compensated in electronic domain
      without resorting to optical techniques. Unlike optical dispersion compensator,
      the electronic equalizer enhances the impairments from the laser phase noise.
      This equalization-enhanced phase noise (EEPN) imposes a tighter constraint on the
      receive laser phase noise for transmission systems with high symbol rate and
      large electronically-compensated chromatic dispersion.

PMID- 18825211
TI  - Electromagnetically induced transparency on GaAs quantum well to observe hole
      spin dephasing.
AB  - Electromagnetically induced transparency (EIT) was observed with transient
      optical response of exciton correlation in GaAs/AlGaAs quantum well structure.
      Decoherence of EIT was increased with temperature (12-60 K), which could be
      simulated by increasing non-radiation decay rate between coherently coupled
      ground states in Bloch equation for Lambda type three level. The non-radiation
      decay was mainly due to hole spin dephasing in the system for EIT via coulomb
      correlation. The hole spin dephasing rate was found with increasing lattice
      temperature and well accorded to the past results of time resolving method with n
      doping material.

PMID- 18825212
TI  - Generation of extended plasma channels in air using femtosecond Bessel beams.
AB  - Extending the longitudinal range of plasma channels created by ultrashort laser
      pulses in atmosphere is important in practical applications of laser-induced
      plasma such as remote spectroscopy and lightning control. Weakly focused
      femtosecond Gaussian beams that are commonly used for generating plasma channels
      offer only a limited control of filamentation. Increasing the pulse energy in
      this case typically results in creation of multiple filaments and does not
      appreciably extend the longitudinal range of filamentation. Bessel beams with
      their extended linear foci intuitively appear to be better suited for generation
      of long plasma channels. We report experimental results on creating extended
      filaments in air using femtosecond Bessel beams. By probing the linear plasma
      density along the filament, we show that apertured Bessel beams produce stable
      single plasma channels that span the entire extent of the linear focus of the
      beam. We further show that by temporally chirping the pulse, the plasma channel
      can be longitudinally shifted beyond the linear-focus zone, an important effect
      that may potentially offer additional means of controlling filament formation.

PMID- 18825213
TI  - Dynamics of microring resonator modulators.
AB  - A dynamic model for the transmission of a microring modulator based on changes in
      the refractive index, loss, or waveguide-ring coupling strength is derived to
      investigate the limitations to the intensity modulation bandwidth. Modulation
      bandwidths approaching the free spectral range frequency are possible if the
      waveguide-ring coupling strength is varied, rather than the refractive index or
      loss of the ring. The results illustrate that via controlled coupling, resonant
      modulators with high quality factors can be designed to operate at frequencies
      much larger than the resonator linewidth.

PMID- 18825214
TI  - Improvement of conversion efficiency for multi-junction solar cells by
      incorporation of Au nanoclusters.
AB  - We studied the photoluminescence (PL) and photovoltaic current-voltage
      characteristics of the three-junction InGaP/InGaAs/Ge solar cells by depositing
      Au nanoclusters on the cell surface. The increases of the PL intensity and short
      circuit current after incorporation of Au nanoclusters are evident. An increase
      of 15.3% in energy conversion efficiency (from 19.6 to 22.6%) is obtained for the
      three-junction solar cells in which Au nanoclusters have been incorporated. We
      suggest that the increased light trapping due to radiative scattering from Au
      nanoclusters is responsible for improving the performance of the three-junction
      solar cells.

PMID- 18825215
TI  - 10.7 Gb/s uncompensated transmission over a 470 km hybrid fiber link with in-line
      SOAs using MLSE and duobinary signals.
AB  - We experimentally demonstrate uncompensated 8-channel wavelength division
      multiplexing (WDM) and single channel transmission at 10.7 Gb/s over a 470 km
      hybrid fiber link with in-line semiconductor optical amplifiers (SOAs). Two
      different forms of the duobinary modulation format are investigated and compared.
      Maximum Likelihood Sequence Estimation (MLSE) receiver technology is found to
      significantly mitigate nonlinear effects from the SOAs and to enable the long
      transmission, especially for optical duobinary signals derived from differential
      phase shift keying (DPSK) signals directly detected after narrowband optical
      filter demodulation. The MLSE also helps to compensate for a non-optimal Fabry
      Perot optical filter demodulator.

PMID- 18825216
TI  - Theory of holographic optical trapping.
AB  - Optical traps use the forces exerted by structured beams of light to confine and
      manipulate microscopic objects in three dimensions. A popular implementation
      involves structuring the trap-forming beam with computer-generated holograms
      before focusing it into traps with a high-numerical-aperture optical train. Here,
      we present a fully vectorial theory for the forces and torques exerted by such
      systems.

PMID- 18825217
TI  - Phased-array cancellation of nonlinear FWM in coherent OFDM dispersive multi-span
      links.
AB  - We develop an analytic model of Coherent Optical Orthogonal Frequency Division
      Multiplexing (OFDM) propagation and detection over multi-span long-haul fiber
      links, comprehensively and rigorously analyzing the impairments due the combined
      effects of FWM, Dispersion and ASE noise. Consistent with prior work of Innoe and
      Schadt in the WDM context, our new closed-form expressions for the total FWM
      received power fluctuations in the wake of dispersive phase mismatch in OFDM
      transmission, indicate that the FWM contributions of the multitude of spans build
      up on a phased-array basis. For particular ultra-long haul link designs, the
      effectiveness of dispersion in reducing FWM is far greater than previously
      assumed in OFDM system analysis. The key is having the dominant FWM
      intermodulation products due to the multiple spans, destructively interfere,
      mutually cancelling their FWM intermodulation products, analogous to operating at
      the null of a phased-array antenna system. By applying the new analysis tools,
      this mode of effectively mitigating the FWM impairment, is shown under specific
      dispersion and spectral management conditions, to substantially suppress the FWM
      power fluctuations. Accounting for the phased-array concept and applying the
      compact OFDM design formulas developed here, we analyzed system performance of a
      40 Gbps coherent OFDM system, over standard G.652 fiber, with cyclic prefix based
      electronic dispersion compensation but no optical compensation along the link.
      The transmission range for 10-3 target BER is almost tripled from 2560 km to 6960
      km, relative to a reference system performing optical dispersion compensation in
      every span (ideally accounting for FWM and ASE noise and the cyclic prefix
      overhead, but excluding additional impairments).

PMID- 18825218
TI  - Laser system generating 250-mJ bunches of 5-GHz repetition rate, 12-ps pulses.
AB  - We report on a high-energy solid-state laser based on a master-oscillator power
      amplifier system seeded by a 5-GHz repetition-rate mode-locked oscillator, aimed
      at the excitation of the dynamic Casimir effect by optically modulating a
      microwave resonator. Solid-state amplifiers provide up to 250 mJ at 1064 nm in a
      500-ns (macro-)pulse envelope containing 12-ps (micro-)pulses, with a
      macro/micropulse format and energy resembling that of near-infrared free-electron
      lasers. Efficient second-harmonic conversion allowed synchronous pumping of an
      optical parametric oscillator, obtaining up to 40 mJ in the range 750-850 nm.

PMID- 18825219
TI  - Retrieval of foreign-broadened water vapor continuum coefficients from emitted
      spectral radiance in the H2O rotational band from 240 to 590 cm(-1).
AB  - The paper presents a novel methodology to retrieve the foreign-broadened water
      vapor continuum absorption coefficients in the spectral range 240 to 590 cm(-1)
      and is the first estimation of the continuum coefficient at wave numbers smaller
      than 400 cm(-1) under atmospheric conditions. The derivation has been
      accomplished by processing a suitable set of atmospheric emitted spectral
      radiance observations obtained during the March 2007 Alps campaign of the ECOWAR
      project (Earth Cooling by WAter vapor Radiation). It is shown that, in the range
      450 to 600 cm(-1), our findings are in good agreement with the widely used
      Mlawer, Tobin-Clough, Kneizys-Davies (MT CKD) continuum. Below 450 cm(-1) however
      the MT CKD model overestimates the magnitude of the continuum coefficient.

PMID- 18825220
TI  - Active laser radar systems with stochastic electromagnetic beams in turbulent
      atmosphere.
AB  - Propagation of stochastic electromagnetic beams through paraxial ABCD optical
      systems operating through turbulent atmosphere is investigated with the help of
      the ABCD matrices and the generalized Huygens-Fresnel integral. In particular,
      the analytic formula is derived for the cross-spectral density matrix of an
      electromagnetic Gaussian Schell-model (EGSM) beam. We applied our analysis for
      the ABCD system with a single lens located on the propagation path, representing,
      in a particular case, the unfolded double-pass propagation scenario of active
      laser radar. Through a number of numerical examples we investigated the effect of
      local turbulence strength and lens' parameters on spectral, coherence and
      polarization properties of the EGSM beam.

PMID- 18825221
TI  - Effective indicators for diagnosis of oral cancer using optical coherence
      tomography.
AB  - A swept-source optical coherence tomography system is used to clinically scan
      oral precancer and cancer patients for statistically analyzing the effective
      indicators of diagnosis. Three indicators are considered, including the standard
      deviation (SD) of an A-mode scan signal profile, the exponential decay constant
      (alpha) of an A-mode-scan spatial-frequency spectrum, and the epithelium
      thickness (T) when the boundary between epithelium and lamina propria can still
      be identified. Generally, in abnormal mucosa, the standard deviation becomes
      larger, the decay constant of the spatial-frequency spectrum becomes smaller, and
      epithelium becomes thicker. The sensitivity and specificity of the three
      indicators are discussed based on universal and individual relative criteria. It
      is found that SD and alpha are good diagnosis indicators for moderate dysplasia
      and squamous cell carcinoma. On the other hand, T is a good diagnosis indicator
      for epithelia hyperplasia and moderate dysplasia.

PMID- 18825222
TI  - Background free CARS imaging by phase sensitive heterodyne CARS.
AB  - In this article we show that heterodyne CARS, based on a controlled and stable
      phase-preserving chain, can be used to measure amplitude and phase information of
      molecular vibration modes. The technique is validated by a comparison of the
      imaginary part of the heterodyne CARS spectrum to the spontaneous Raman spectrum
      of polyethylene. The detection of the phase allows for rejection of the non
      resonant background from the data. The resulting improvement of the signal to
      noise ratio is shown by measurements on a sample containing lipid.

PMID- 18825223
TI  - The double dark resonance in a cold gas of Cs atoms and molecules.
AB  - We theoretically investigated the properties of the effective four-level
      stimulated Raman adiabatic passage scheme in a cold gas of Cs atoms and
      molecules, where exists the tunnelling coupling between two excited molecular
      states due to the 0(g)- (6S,6P(3/2)) double well structure. The double dark
      resonance is predicted in the absorption spectrum when the tunnelling coupling
      strength is large enough. The double dark resonance not only reveals the
      formation of the ultra-cold molecules, but also provides further evidence for the
      tunnelling as one effective coupling mechanism between the two excited molecular
      states. The effect of the various experimental conditions on this phenomena has
      been discussed.

PMID- 18825224
TI  - Compact optical temporal differentiator based on silicon microring resonator.
AB  - We propose and experimentally demonstrate a temporal differentiator in optical
      field based on a silicon microring resonator with a radius of 40 microm. The
      microring resonator operates near the critical coupling region, and can take the
      first order derivative of the optical field. It features compact size thus is
      suitable for integration with silicon-on-insulator (SOI) based optical and
      electronic devices. The performance of this optical differentiator is tested
      using signals with typical shapes such as Gaussian, sinusoidal and square-like
      pulses at data rates of 10 Gb/s and 5 Gb/s.

PMID- 18825225
TI  - Reconfigurable microfluidic photonic crystal slab cavities.
AB  - We demonstrate the spectral and spatial reconfigurability of photonic crystal
      double-heterostructure cavities in silicon by microfluidic infiltration of
      selected air holes. The lengths of the microfluidic cavities are changed by
      adjusting the region of infiltrated holes in steps of several microns. We
      systematically investigate the spectral signature of these cavities, showing high
      Q-factor resonances for a broad range of cavity lengths. The fluid can be removed
      by immersing the device in toluene, offering complete reconfigurability. Our
      cavity writing technique allows for tolerances in the infiltration process and
      provides flexibility as it can be employed at any time after photonic crystal
      fabrication.

PMID- 18825226
TI  - Independent polarisation control of multiple optical traps.
AB  - We present a system which uses a single spatial light modulator to control the
      spin angular momentum of multiple optical traps. These traps may be independently
      controlled both in terms of spatial location and in terms of their spin angular
      momentum content. The system relies on a spatial light modulator used in a "split
      screen" configuration to generate beams of orthogonal polarisation states which
      are subsequently combined at a polarising beam splitter. Defining the phase
      difference between the beams with the spatial light modulator enables control of
      the polarisation state of the light. We demonstrate the functionality of the
      system by controlling the rotation and orientation of birefringent vaterite
      crystals within holographic optical tweezers.

PMID- 18825227
TI  - Fabrication and phase modulation in organic single-crystalline configurationally
      locked, phenolic polyene OH1 waveguides.
AB  - A novel and promising technique for the fabrication of electro-optically active
      single crystalline organic waveguides from 2-{3-(4-hydroxystyryl)-5,5
      dimethylcyclohex-2-enylidene}malononitrile (OH1) is presented. OH1 is an
      interesting material for photonic applications due to the large electro-optic
      coefficients (r333 = 109+/-4 pm/V at 632.8 nm) combined with a relatively high
      crystal symmetry (orthorhombic with point group mm2). Due to the very favorable
      growth characteristics, large-area (> 150 mm(2)) single crystalline thin films
      with very good optical quality and thickness between 0.05-10 microm have been
      grown on amorphous glass substrates. We have developed and optimized optical
      lithography and reactive ion etching processes for the fabrication of wire
      optical waveguides with dimensions of w x h = 3.4 x 3.5 microm(2) and above. The
      technique is capable of producing low loss integrated optical waveguides having
      propagation losses of 2 dB/cm with a high refractive index contrast between core
      cladding and core-substrate of delta n = 1.23 and 0.72, respectively at 980 nm.
      Electro-optic phase modulation in these waveguides has been demonstrated at 632.8
      nm and 852 nm. Calculations show that with an optimized electrode configuration
      the half-wave voltage x length product V(pi) x L can be reduced from 8.4 Vcm, as
      obtained in our device, to 0.3 Vcm in the optimized case. This allows for the
      fabrication of sub-1 V half-wave voltage, organic electro-optic modulators with
      highly stable chromophore orientation.

PMID- 18825228
TI  - Optical 4x4 hitless slicon router for optical networks-on-chip (NoC).
AB  - We demonstrate here a spatially non-blocking optical 4x4 router with a footprint
      of 0.07 mm(2) for use in future integrated photonic interconnection networks. The
      device is dynamically switched using thermo-optically tuned silicon microring
      resonators with a wavelength shift to power ratio of 0.25nm/mW. The design can
      route four optical inputs to four outputs with individual bandwidths of up to
      38.5 GHz. All tested configurations successfully routed a single-wavelength laser
      and provided a maximum extinction ratio larger than 20 dB.

PMID- 18825229
TI  - Quasi-phase-matching and dispersion characterization of harmonic generation in
      the perturbative regime using counterpropagating beams.
AB  - It is shown theoretically that second harmonic generation can be quasi-phase
      matched by using a pump beam consisting of a forward propagating field and a
      counterpropagating pulse train. The counterpropagating setup can also be used for
      direct measurement of the coherence length of the nonlinear process which can
      determine the dispersion properties of the medium.

PMID- 18825230
TI  - Efficient visible laser emission of GaN laser diode pumped Pr-doped fluoride
      scheelite crystals.
AB  - In the present work we report on the growth, spectroscopy and laser results of
      diode pumped Pr-doped LiYF(4), LiLuF(4) and LiGdF(4) fluoride, scheelite-type
      structure crystals. We measured the polarisation dependent absorption and
      emission properties as well as the decay time of the (3)P(0) level. Exploiting
      the (3)P(2) absorption around 444 nm, we obtained efficient laser emission under
      GaN laser diode pumping on several transitions from the green to the near
      infrared wavelength range.

PMID- 18825231
TI  - Three-dimensional parallel holographic micropatterning using a spatial light
      modulator.
AB  - We present a micropatterning method for the automatic transfer and arbitrary
      positioning of computer-generated three-dimensional structures within a
      substrate. The Gerchberg-Saxton algorithm and an electrically addressed spatial
      light modulator (SLM) are used to create and display phase holograms,
      respectively. A holographic approach to light manipulation enables arbitrary and
      efficient parallel photo-patterning. Multiple pyramidal microstructures were
      created simultaneously in a photosensitive adhesive. A scanning electron
      microscope was used to confirm successful replication of the desired microscale
      structures.

PMID- 18825232
TI  - Specific detection of proteins using photonic crystal waveguides.
AB  - Specific detection of proteins is demonstrated using planar photonic crystal
      waveguides. Using immobilized biotin as probe, streptavidin was captured, causing
      the waveguide mode cut-off to red-shift. The device was shown to detect a 2.5 nm
      streptavidin film with a 0.86 nm cut-off red-shift. An improved photonic crystal
      waveguide sensor design is also described and shown to have a 40% improved bulk
      refractive index response.

PMID- 18825233
TI  - Accurate frequency alignment in fabrication of high-order microring-resonator
      filters.
AB  - Frequency mismatch in high-order microring-resonator filters is investigated. We
      demonstrate that this frequency mismatch is caused mainly by the intrafield
      distortion of scanning-electron-beam-lithography (SEBL) used in fabrication. The
      intrafield distortion of an SEBL system is measured, and a simple method is also
      proposed to correct this distortion. By applying this correction method, the
      average frequency mismatch in second-order microring-resonator filters was
      reduced from -8.6 GHz to 0.28 GHz.

PMID- 18825234
TI  - Passively mode-locked GaInNAs disk laser operating at 1220 nm.
AB  - We report an optically-pumped semiconductor disk laser passively mode-locked with
      a semiconductor saturable-absorber mirror. Both the absorber and the gain media
      were made of dilute nitride compound semiconductor, GaInNAs, which enables
      operation around 1.2 microm wavelengths. The laser generated 5 ps optical pulses
      with an average output power up to 275 mW. Our demonstration provides an
      attractive approach for efficiently generating red-wavelengths through external
      cavity frequency doubling.

PMID- 18825235
TI  - Brillouin scattering spectra in high-power single-frequency ytterbium doped fiber
      amplifiers.
AB  - We report on theoretical and experimental investigations on spontaneous and
      stimulated Brillouin scattering during operation of a high-power single-frequency
      polarization-maintaining ytterbium doped fiber amplifier. For different amplifier
      configurations with co- and counter-propagating seed and pump radiation the
      evolution of Brillouin scattering spectra was investigated with a heterodyne
      detection scheme. Spontaneous Brillouin gain spectra at low powers were
      additionally investigated using a pump-probe technique. The data obtained from
      these experiments have been compared with a theoretical model based on coupled
      intensity equations. A Brillouin scattering suppression has been investigated
      theoretically and experimentally with externally applied temperature gradients
      along the fiber resulting in up to 3.5 dB suppression and 115 W of amplifier
      output power.

PMID- 18825236
TI  - Laser frequency stabilization and control through offset sideband locking to
      optical cavities.
AB  - We describe a class of techniques whereby a laser frequency can be stabilized to
      a fixed optical cavity resonance with an adjustable offset, providing a wide
      tuning range for the central frequency. These techniques require only minor
      modifications to the standard Pound-Drever-Hall locking techniques and have the
      advantage of not altering the intrinsic stability of the frequency reference. We
      discuss the expected performance and limitations of these techniques and present
      a laboratory investigation in which both the sideband techniques and the
      standard, on-tunable Pound-Drever- Hall technique reached the 100Hz/square
      root(Hz) level.

PMID- 18825237
TI  - Aspheric lenses for terahertz imaging.
AB  - We present novel designs for aspheric lenses used in terahertz (THz) imaging. As
      different surfaces result in different beam shaping properties and in different
      losses from reflection and absorption, the resultant imaging resolution (i.e. the
      focal spot size) depends critically on the design approach. We evaluate the
      different lens designs using Kirchhoff's scalar diffraction theory, and test the
      predictions experimentally. We also show that our lenses can achieve sub
      wavelength resolution. While our lens designs are tested with THz radiation, the
      design considerations are applicable also to other regions of the electro
      magnetic spectrum.

PMID- 18825238
TI  - Simultaneous chromatic dispersion, polarization-mode-dispersion and OSNR
      monitoring at 40Gbit/s.
AB  - A novel method for independent and simultaneous monitoring of chromatic
      dispersion (CD), first-order PMD and OSNR in 40Gbit/s systems is proposed and
      demonstrated. This is performed using in-band tone monitoring of 5GHz, optically
      down-converted to a low intermediate-frequency (IF) of 10kHz. The measurement
      provides a large monitoring range with good accuracies for CD (4742+/-100ps/nm),
      differential group delay (DGD) (200+/-4ps) and OSNR (23+/-1dB), independently of
      the bit-rate. In addition, the use of electro-absorption modulators (EAM) for the
      simultaneous down-conversion of all channels and the use of low-speed detectors
      makes it cost effective for multi-channel operation.

PMID- 18825239
TI  - Measuring optical tunneling times using a Hong-Ou-Mandel interferometer.
AB  - We report a prediction for the delay measured in an optical tunneling experiment
      using Hong-Ou-Mandel (HOM) interference, taking into account the Goos-Hanchen
      shift generalized to frustrated total internal reflection situations. We
      precisely state assumptions under which the tunneling delay measured by an HOM
      interferometer can be calculated. We show that, under these assumptions, the
      measured delay is the group delay, and that it is apparently 'superluminal' for
      sufficiently thick air gaps. We also show how an HOM signal with multiple minima
      can be obtained, and that the shape of such a signal is not appreciably affected
      by the presence of the optical tunneling zone, thus ruling out the explanation of
      the anomalously short tunneling delays in terms of a reshaping of the wavepacket
      as it goes through the tunneling zone. Finally, we compare the predicted
      tunneling delay to a relevant classical delay and conclude that our predictions
      involve no non-causal effect.

PMID- 18825240
TI  - High-sensitivity temperature-independent differential pressure sensor using fiber
      Bragg gratings.
AB  - By means of novel packaged-structure design, a temperature independent
      differential pressure sensor based on fiber Bragg gratings with high sensitivity
      is experimentally demonstrated. The differential pressure sensitivity of the
      sensor can reach to 821.87nm/MPa. This device can also be used for simultaneous
      measurement of temperature and differential pressure, which is suitable for
      applications involving measurement of liquid level, liquid density or specific
      gravity detection.

PMID- 18825241
TI  - 2.3 W single transverse mode thulium-doped ZBLAN fiber laser at 1480 nm.
AB  - A 2.3 W single transverse mode thulium-doped fluoride fiber laser based on fiber
      Bragg gratings is presented. The laser has a conversion efficiency of 65% to be
      compared to the quantum limit of 72%. The performances of the laser are compared
      for two pump wavelengths of 1040 and 1064 nm and are analyzed based on a rate
      equation analysis.

PMID- 18825242
TI  - Observation of large 10-Gb/s SBS slow light delay with low distortion using an
      optimized gain profile.
AB  - An optimum SBS gain profile is designed to achieve better slow-light performance.
      It consists of a nearly flat-top profile with sharp edges. Tunable delays up to 3
      pulse widths for 100-ps-long input pulses, corresponding to 10 Gb/s data rates,
      are found while keeping an output-input pulse-width ratio below 1.8. Bit-error
      rate (BER) measurements performed for a non-return-to-zero modulation format
      demonstrates 28 ps of delay under error-free operation.

PMID- 18825243
TI  - Cutoff wavelength of ridge waveguide near field transducer for disk data storage.
AB  - The electromagnetic eigenmodes of and light transmission through a C-aperture to
      the far field, and to a storage medium, have been studied based on the full
      vectorial finite difference method. It is found that the cutoff wavelength of C
      aperture waveguides in a gold film is much longer than that in a perfect electric
      conductor, and the fundamental mode is confined in the gap and polarized with the
      electric field along the gap. The light transmission resonance through C
      apertures to far field and to a storage medium occurs at wavelengths below the
      waveguide cutoff wavelength. Measurements on the fabricated C-apertures confirm
      the mode confinement and transmission resonance.

PMID- 18825244
TI  - Broadband source of telecom-band polarization-entangled photon-pairs for
      wavelength-multiplexed entanglement distribution.
AB  - Studies on telecom-band entangled photon-pair sources for entanglement
      distribution have so far focused on their narrowband operations. Fiber-based
      sources are seriously limited by spontaneous Raman scattering while sources based
      on quasi-phase-matched crystals or waveguides are usually narrowband because of
      long device lengths and/or operations far from degeneracy. An entanglement
      distributor would have to multiplex many such narrowband sources before
      entanglement distribution to fully utilize the available fiber transmission
      bandwidth. In this work, we demonstrate a broadband source of polarization
      entangled photon-pairs suitable for wavelength-multiplexed entanglement
      distribution over optical fiber. We show that our source is potentially capable
      of simultaneously supporting up to forty-four independent wavelength channels.

PMID- 18825245
TI  - Nonlinear properties of split-ring resonators.
AB  - In this letter, the properties of split-ring resonators (SRRs) loaded with high-Q
      capacitors and nonlinear varactors are theoretically analyzed and experimentally
      measured. We demonstrate that the resonance frequency f(m) of the nonlinear SRRs
      can be tuned by increasing the incident power. f(m) moves to lower and higher
      frequencies for the SRR loaded with one varactor and two back-to-back varactors,
      respectively. For high incident powers, we observe bistable tunable metamaterials
      and hysteresis effects. Moreover, the coupling between two nonlinear SRRs is also
      discussed.

PMID- 18825247
TI  - Performance evaluation and assessment of receiver impairments of a novel PolSK
      transceiver based on differential demodulation.
AB  - We present a novel transceiver setup for Polarization Shift Keying (PolSK)
      modulation using a simple transmitter and a receiver based on differential
      demodulation. The transmitter is made up of a LiNbO(3) phase modulator with the
      input fiber pigtailed at 45 degrees with respect to the principal axes of the
      modulator. The receiver is composed of an asymmetric Mach-Zehnder Interferometer
      (AMZI) and a couple of balanced photodetectors (BPD), as usually employed for
      receiving DPSK. To our knowledge, it is the first time such receiver structure is
      applied to PolSK. In order to fully assess the system performance of the proposed
      setup, we have carried out numerical simulations using a semi-analytical
      technique for bit-error-rate evaluation and performed experimental measurements
      at 10 Gbit/s. After having optimized transceiver performances, we evaluated the
      resilience to receiver impairments to verify the viability of a realistic
      implementation. Surprisingly, PolSK shows a better sensitivity using a single-end
      receiver (with the AMZI tuned at the minimum transmittance point) than using a
      balanced one. Another improvement has been obtained optimizing the driving
      voltage at the transmitter: this leads to a "non-ideal" PolSK modulation with non
      orthogonal symbols, which shows an enhanced performance thanks to a synchronous
      phase modulation.

PMID- 18825246
TI  - Dynamic functional and mechanical response of breast tissue to compression.
AB  - Physiological tissue dynamics following breast compression offer new contrast
      mechanisms for evaluating breast health and disease with near infrared
      spectroscopy. We monitored the total hemoglobin concentration and hemoglobin
      oxygen saturation in 28 healthy female volunteers subject to repeated fractional
      mammographic compression. The compression induces a reduction in blood flow, in
      turn causing a reduction in hemoglobin oxygen saturation. At the same time, a two
      phase tissue viscoelastic relaxation results in a reduction and redistribution of
      pressure within the tissue and correspondingly modulates the tissue total
      hemoglobin concentration and oxygen saturation. We observed a strong correlation
      between the relaxing pressure and changes in the total hemoglobin concentration
      bearing evidence of the involvement of different vascular compartments.
      Consequently, we have developed a model that enables us to disentangle these
      effects and obtain robust estimates of the tissue oxygen consumption and blood
      flow. We obtain estimates of 1.9+/-1.3 micromol/100 mL/min for OC and 2.8+/-1.7
      mL/100 mL/min for blood flow, consistent with other published values.

PMID- 18825248
TI  - Short-wavelength MEMS-tunable VCSELs.
AB  - We present electrically-injected MEMS-tunable vertical-cavity surface-emitting
      lasers with emission wavelengths below 800 nm. Operation in this wavelength
      range, near the oxygen A-band from 760-780 nm, is attractive for absorption-based
      optical gas sensing. These fully-monolithic devices are based on an oxide
      aperture AlGaAs epitaxial structure and incorporate a suspended dielectric Bragg
      mirror for wavelength tuning. By implementing electrostatic actuation, we
      demonstrate the potential for tuning rates up to 1 MHz, as well as a wide
      wavelength tuning range of 30 nm (767-737 nm).

PMID- 18825249
TI  - Localized surface plasmon resonance effects on the magneto-optical activity of
      continuous Au/Co/Au trilayers.
AB  - We study how the magneto-optical activity in polar configuration of continuous
      Au/Co/Au trilayers is affected by the excitation of localized plasmon resonances
      of an array of Au nanodiscs fabricated on top of them over a dielectric SiO(2)
      spacer. We show that the effect of the nanodiscs array is twofold. First, it
      optimizes the absorption of light at specific photon energies corresponding to
      the localized surface plasmon excitation of the array, modifying the reflectivity
      of the system (we define this effect as the purely optical contribution). Second,
      upon localized plasmon resonance excitation, the electromagnetic field in the
      whole system is redistributed, and an enhanced magneto-optical activity occurs at
      those energies where the electromagnetic field in the magnetic layer is increased
      (this effect is identified as the purely magneto-optical contribution of the
      nanodiscs array).

PMID- 18825250
TI  - Surface plasmonic lasing via the amplification of coupled surface plasmon waves
      inside dielectric-metal-dielectric waveguides.
AB  - Coupling of surface plasmon (SP) waves between two metal-dielectric interfaces of
      a dielectric-metal-dielectric (DMD) waveguide, in which one of the dielectric
      layers is incorporated with optical gain, is proposed to realize plasmonic
      lasing. The propagation characteristics of the SP waves supported inside the DMD
      waveguides are studied by finite-difference time-domain method. It is found that
      there are optimized thicknesses for the metal film and gain region to obtain
      minimum propagation loss. Furthermore, a coupled-mode model is developed to
      analyze the lasing characteristics of the DMD waveguides with coherent optical
      feedback. The conditions to achieve single-longitudinal-mode lasing from the DMD
      waveguides are also investigated.

PMID- 18825251
TI  - Impact of XPM and FWM on the digital implementation of impairment compensation
      for WDM transmission using backward propagation.
AB  - The impact of cross-phase modulation (XPM) and four-wave mixing (FWM) on
      electronic impairment compensation via backward propagation is analyzed. XPM and
      XPM+FWM compensation are compared by solving, respectively, the backward coupled
      Nonlinear Schrodinger Equation (NLSE) system and the total-field NLSE. The DSP
      implementations as well as the computational requirements are evaluated for each
      post-compensation system. A 12 x 100 Gb/s 16-QAM transmission system has been
      used to evaluate the efficiency of both approaches. The results show that XPM
      post-compensation removes most of the relevant source of nonlinear distortion.
      While DSP implementation of the total-field NLSE can ultimately lead to more
      precise compensation, DSP implementation sing the coupled NLSE system can
      maintain high accuracy with better computation efficiency and low system latency.

PMID- 18825252
TI  - An analytical approach to estimating aberrations in curved multilayer optics for
      hard x-rays: 2. Interpretation and application to focusing experiments.
AB  - Aberration effects are studied in parabolic and elliptic multilayer mirrors for
      hard x-rays, basing on a simple analytical approach. The interpretation of the
      underlying equations provides insight into fundamental limitations of the
      focusing properties of curved multilayers. Using realistic values for the
      multilayer parameters the potential impact on the broadening of the focal spot is
      evaluated. Within the limits of this model, systematic contributions to the spot
      size can be described. The work is complemented by a comparison with experimental
      results obtained with a W/B(4)C curved multilayer mirror.

PMID- 18825253
TI  - Collagen and myosin characterization by orientation field second harmonic
      microscopy.
AB  - Collagen and myosin fibrils are endogenous harmonophores that both give rise to
      Second Harmonic Generation (SHG). By combining four polarization SHG images
      provided by a scanning microscope, we show that the orientation of the principal
      axis of the nonlinear susceptibility tensor chi(2) can be determined for each
      pixel of the image. The ratio rho = chi33/chi15 of the principal components of
      chi(2) of collagen and myosin was obtained with the same method, and found within
      the range 1.6-1.8 and 0.5-0.6 respectively. The orientation of the principal axis
      of chi(2) is shown to be correlated to the orientation of the fibrils themselves.
      This provides a straightforward method, which we call Orientation Field-Second
      Harmonic Microscopy (OF-SHM), to reconstruct orientation fields of fibrils at
      various scales and resolutions in different biological systems (from muscle
      sarcomere to the whole embryo).

PMID- 18825254
TI  - Single SOA based 16 DWDM channels all-optical NRZ-to-RZ format conversions with
      different duty cycles.
AB  - We demonstrate simultaneous NRZ-to-RZ conversion for 16 DWDM channels, using a
      single SOA and a subsequent delay interferometer (DI) acting as a comb-like
      filter to control the obtained pulse-width for all of the channels. The SOA is
      operated in deep saturation, resulting in weak cross gain modulation and cross
      phase modulation induced crosstalk between different NRZ channels. By adjusting
      the detuning between the peaks in the DI spectrum and each corresponding carrier,
      good quality RZ signals with different duty cycles can be achieved. Bit-error
      rate measurements show negative power penalties for the obtained RZ signals with
      different duty cycles. Significant timing jitter reductions for all channels show
      the good regenerative performance of the proposed converter.

PMID- 18825255
TI  - Criterion for keeping completely unpolarized or completely polarized stochastic
      electromagnetic Gaussian Schell-model beams on propagation.
AB  - The cross-spectral density matrixes of electromagnetic Gaussian Schell-model
      sources that are completely unpolarized or completely polarized are derived. We
      find that both the completely unpolarized stochastic electromagnetic Gaussian
      Schell-model beam and the completely polarized stochastic electromagnetic
      Gaussian Schell-model beam will keep their spectral degree of polarization or
      become partially polarized under different constraint conditions during their
      propagation in free space or through turbulent atmosphere. We give necessary
      theoretical explanation to the physical phenomena. They are considered as
      coherence-induced polarization changes and spectral density-induced polarization
      changes.

PMID- 18825256
TI  - Measurement of polarization dependent loss, polarization mode dispersion and
      group delay of optical components using swept optical single sideband modulated
      signals.
AB  - We introduce a novel method for high wavelength-resolution measurement of
      polarization-averaged group delay, polarization dependent loss and polarization
      mode dispersion of optical components using swept optical single sideband
      modulated signals. Measurements of a phase-shifted fiber Bragg grating, a chirped
      fiber Bragg grating and of the Brillouin spectra of a length of fiber are used in
      order to demonstrate the technique.

PMID- 18825257
TI  - Entangled-photon coincidence fluorescence imaging.
AB  - We describe fluorescence imaging using the second-order correlation of entangled
      photon pairs. The proposed method is based on the principle that one photon of
      the pair carries information on where the other photon has been absorbed and has
      produced fluorescence in a sample. Because fluorescent molecules serve as
      "detectors" breaking the entanglement, multiply-scattered fluorescence photons
      within the sample do not cause image blur. We discuss experimental
      implementations.

PMID- 18825258
TI  - The characteristics of compound diffractive telescope.
AB  - Compound diffractive telescope is a new type of space optical system. It applies
      the structure of compound eyes into diffractive telescopes. With the help of
      diffractive optical element, the optical system could become lighter in weight,
      lower in cost, and looser in sensitivity to manufacturing tolerance. And with the
      help of compound eyes structure, the field of view is expanded. A demonstrated
      system of compound diffractive telescope is given. It is composed of one 50mm
      aperture primary diffractive lens and twenty-one eyepieces. The characteristics
      of the system are analysed by testing its star image and resolution. It is shown
      that the whole system can provide about diffraction limit imaging within 4.2
      degree field of view.

PMID- 18825259
TI  - Single-mode waveguide optical isolator based on direction-dependent cutoff
      frequency.
AB  - A single-mode-waveguide optical isolator based on propagation direction dependent
      cut-off frequency is proposed. The isolation bandwidth is the difference between
      the cut-off frequencies of the lowest forward and backward propagating modes.
      Perturbation theory is used for analyzing the correlation between the material
      distribution and the bandwidth. The mode profile determines an appropriate
      distribution of non-reciprocal materials.

PMID- 18825260
TI  - Ion implanted optical channel waveguides in Er3+/MgO co-doped near stoichiometric
      LiNbO3: a new candidate for active integrated photonic devices operating at 1.5
      microm.
AB  - We report on the fabrication of active optical channel waveguides in Er(3+)/MgO
      co-doped near stoichiometric lithium niobate crystals by means of selective low
      dose oxygen ion implantation through a specially designed photoresist stripe
      mask. After post-implantation treatment at 260 degrees C for 1 h, the channel
      waveguides possess a propagation loss of approximately 1.7 dB/cm. The micro
      luminescence investigation reveals that fluorescence emissions at approximately
      1.5 microm in the waveguides are well preserved with respect to the bulk,
      exhibiting possible applications for integrated active photonic devices.

PMID- 18825261
TI  - Low loss photonic components in high index bismuth borate glass by femtosecond
      laser direct writing.
AB  - Single mode, low loss waveguides were fabricated in high index bismuth borate
      glass by femtosecond laser direct writing. A specific set of writing parameters
      leading to waveguides perfectly mode matched to standard single-mode fibers at
      1.55 microm with an overall insertion loss of approximately 1 dB and with
      propagation loss below 0.2 dB/cm was identified. Photonic components such as Y
      splitters and directional couplers were also demonstrated. A close agreement
      between their performances and theoretical predictions based upon the
      characterization of the waveguide properties is shown. Finally, the nonlinear
      refractive index of the waveguides has been measured to be 6.6 x 10(-15) cm(2)/W
      by analyzing self-phase modulation of the propagating femtosecond laser pulse at
      the wavelength of 1.46 microm. Broadening of the transmitted light source as
      large as 500 nm was demonstrated through a waveguide with the length of 1.8 cm.

PMID- 18825262
TI  - Quantitative spectroscopic imaging for non-invasive early cancer detection.
AB  - We report a fully quantitative spectroscopy imaging instrument for wide area
      detection of early cancer (dysplasia). This instrument provides quantitative maps
      of tissue biochemistry and morphology, making it a potentially powerful
      surveillance tool for objective early cancer detection. We describe the design,
      construction, calibration, and first clinical application of this new system. We
      demonstrate its accuracy using physical tissue models. We validate its diagnostic
      ability on a resected colon adenoma, and demonstrate feasibility of in vivo
      imaging in the oral cavity.

PMID- 18825263
TI  - Synthetic aperture tomographic phase microscopy for 3D imaging of live cells in
      translational motion.
AB  - We present a technique for 3D imaging of live cells in translational motion
      without need of axial scanning of objective lens. A set of transmitted electric
      field images of cells at successive points of transverse translation is taken
      with a focused beam illumination. Based on Hyugens' principle, angular plane
      waves are synthesized from E-field images of a focused beam. For a set of
      synthesized angular plane waves, we apply a filtered back-projection algorithm
      and obtain 3D maps of refractive index of live cells. This technique, which we
      refer to as synthetic aperture tomographic phase microscopy, can potentially be
      combined with flow cytometry or microfluidic devices, and will enable high
      throughput acquisition of quantitative refractive index data from large numbers
      of cells.

PMID- 18825264
TI  - Optical snakes and ladders: dispersion and nonlinearity in microcoil resonators.
AB  - Microcoil resonators are a radical new geometry for high Q resonators with unique
      linear features. In this paper I briefly summarise their linear properties before
      extending the analysis to nonlinear interactions in microcoil resonators. As
      expected such nonlinear resonators are bistable and exhibit hysteresis. Finally I
      discuss possible applications and extensions to such resonators.

PMID- 18825265
TI  - Wavelength and loss splitting in directly coupled photonic-crystal defect
      microcavities.
AB  - Coupling between photonic-crystal defect microcavities is observed to result in a
      splitting not only of the mode wavelength but also of the modal loss. It is
      discussed that the characteristics of the loss splitting may have an important
      impact on the optical energy transfer between the coupled resonators. The loss
      splitting--given by the imaginary part of the coupling strength--is found to
      arise from the difference in diffractive out-of-plane radiation losses of the
      symmetric and the antisymmetric modes of the coupled system. An approach to
      control the splitting via coupling barrier engineering is presented.

PMID- 18825266
TI  - Origin of periodicity in nanostructuring on thin film surfaces ablated with
      femtosecond laser pulses.
AB  - We report physical processes responsible for the periodic nanostructure formation
      in femtosecond-laser ablation of thin film surfaces. It has been found that an
      initial random distribution of nanoscale ablation traces is periodically
      structured with an increase in superimposed laser pulses or fluence on diamond
      like carbon film used as the target. The results show that the formation of
      periodicity can be attributed to the excitation of surface plasmon polaritons to
      induce the periodic enhancement of local fields in the surface layer. The
      estimated field period is in good agreement with the observed size of
      nanostructures.

PMID- 18825267
TI  - Plastinated tissue samples as three-dimensional models for optical instrument
      characterization.
AB  - Histology of biological specimens is largely limited to investigating two
      dimensional structure because of the sectioning required to produce optically
      thin samples for conventional microscopy. With the advent of three-dimensional
      optical imaging technologies such as optical coherence tomography (OCT), diffuse
      optical tomography (DOT), and multiphoton microscopy (MPM), methods of tissue
      preparation that minimally disrupt three-dimensional structure are needed. We
      propose plastination as a means of transforming tissues into three-dimensional
      models suitable for optical instrument characterization. Tissues are plastinated
      by infusing them with transparent polymers, after which they can be safely
      handled, unlike fresh or fixed tissues. Such models are useful for investigating
      three-dimensional structure, testing and comparing the performance of optical
      instruments, and potentially investigating tissue properties not normally
      observed after the three-dimensional scattering properties of a biological
      samples are lost. We detail our plastination procedures and show examples of
      imaging several plastinated tissues from a pre-clinical rat model using optical
      coherence tomography.

PMID- 18825268
TI  - Biomimetic modeling of copper complexes: a study of enantioselective catalytic
      oxidation on d-(+)-catechin and L-( - )-epicatechin with copper complexes.
AB  - The biomimetic catalytic oxidations of the dinuclear and trinuclear copper(II)
      complexes versus two catechols, namely, D-(+)-catechin and L-( - )-epicatechin to
      give the corresponding quinones are reported. The unstable quinones were trapped
      by the nucleophilic reagent, 3-methyl-2-benzothiazolinone hydrazone (MBTH), and
      have been calculated the molar absorptivities of the different quinones. The
      catalytic efficiency is moderate, as inferred by kinetic constants, but the
      complexes exhibit significant enantio-differentiating ability towards the
      catechols, albeit for the dinuclear complexes, this enantio-differentiating
      ability is lower. In all cases, the preferred enantiomeric substrate is D-(+)
      catechin to respect the other catechol, because of the spatial disposition of
      this substrate.

PMID- 18825269
TI  - Neonatal and infantile immune responses to encapsulated bacteria and conjugate
      vaccines.
AB  - Encapsulated bacteria are responsible for the majority of mortality among
      neonates and infants. The major components on the surface of these bacteria are
      polysaccharides which are important virulence factors. Immunity against these
      components protects against disease. However, most of the polysaccharides are
      thymus-independent (TI)-2 antigens which induce an inadequate immune response in
      neonates and infants. The mechanisms that are thought to play a role in the
      unresponsiveness of this age group to TI-2 stimuli will be discussed. The lack of
      immune response may be overcome by conjugating the polysaccharides to a carrier
      protein. This transforms bacterial polysaccharides from a TI-2 antigen into a
      thymus-dependent (TD) antigen, thereby inducing an immune response and
      immunological memory in neonates and infants. Such conjugated vaccines have been
      shown to be effective against the most common causes of invasive disease caused
      by encapsulated bacteria in neonates and children. These and several other
      approaches in current vaccine development will be discussed.

PMID- 18825270
TI  - Cerebral blood flow measurement using fMRI and PET: a cross-validation study.
AB  - An important aspect of functional magnetic resonance imaging (fMRI) is the study
      of brain hemodynamics, and MR arterial spin labeling (ASL) perfusion imaging has
      gained wide acceptance as a robust and noninvasive technique. However, the
      cerebral blood flow (CBF) measurements obtained with ASL fMRI have not been fully
      validated, particularly during global CBF modulations. We present a comparison of
      cerebral blood flow changes (DeltaCBF) measured using a flow-sensitive
      alternating inversion recovery (FAIR) ASL perfusion method to those obtained
      using H(2) (15)O PET, which is the current gold standard for in vivo imaging of
      CBF. To study regional and global CBF changes, a group of 10 healthy volunteers
      were imaged under identical experimental conditions during presentation of 5
      levels of visual stimulation and one level of hypercapnia. The CBF changes were
      compared using 3 types of region-of-interest (ROI) masks. FAIR measurements of
      CBF changes were found to be slightly lower than those measured with PET (average
      DeltaCBF of 21.5 +/- 8.2% for FAIR versus 28.2 +/- 12.8% for PET at maximum
      stimulation intensity). Nonetheless, there was a strong correlation between
      measurements of the two modalities. Finally, a t-test comparison of the slopes of
      the linear fits of PET versus ASL DeltaCBF for all 3 ROI types indicated no
      significant difference from unity (P > .05).

PMID- 18825271
TI  - Pervasive health care services and technologies.

PMID- 18825272
TI  - Transthyretin and amyloid in the islets of Langerhans in type-2 diabetes.
AB  - Transthyretin (TTR) is a major amyloid fibril protein in certain systemic forms
      of amyloidosis. It is a plasma protein, mainly synthesized by the liver but
      expression occurs also at certain minor locations, including the endocrine cells
      in the islets of Langerhans. With the use of immunohistochemistry and in situ
      hybridization, we have studied the distribution of transthyretin-containing cells
      in islets of Langerhans in type-2 diabetic and nondiabetic individuals. TTR
      expression was particularly seen in alpha (glucagon) cells. Islets from type-2
      diabetic patients had proportionally more transthyretin-reactive islet cells,
      including beta cells. A weak transthyretin immunoreaction in IAPP-derived amyloid
      occurred in some specimens. In seeding experiments in vitro, we found that TTR
      fibrils did not seed IAPP while IAPP fibrils seeded TTR. It is suggested that
      islet expression of transthyretin may be altered in type-2 diabetes.

PMID- 18825273
TI  - Evidence for avian intrathoracic air sacs in a new predatory dinosaur from
      Argentina.
AB  - BACKGROUND: Living birds possess a unique heterogeneous pulmonary system composed
      of a rigid, dorsally-anchored lung and several compliant air sacs that operate as
      bellows, driving inspired air through the lung. Evidence from the fossil record
      for the origin and evolution of this system is extremely limited, because lungs
      do not fossilize and because the bellow-like air sacs in living birds only rarely
      penetrate (pneumatize) skeletal bone and thus leave a record of their presence.
      METHODOLOGY/PRINCIPAL FINDINGS: We describe a new predatory dinosaur from Upper
      Cretaceous rocks in Argentina, Aerosteon riocoloradensis gen. et sp. nov., that
      exhibits extreme pneumatization of skeletal bone, including pneumatic hollowing
      of the furcula and ilium. In living birds, these two bones are pneumatized by
      diverticulae of air sacs (clavicular, abdominal) that are involved in pulmonary
      ventilation. We also describe several pneumatized gastralia ("stomach ribs"),
      which suggest that diverticulae of the air sac system were present in surface
      tissues of the thorax. CONCLUSIONS/SIGNIFICANCE: We present a four-phase model
      for the evolution of avian air sacs and costosternal-driven lung ventilation
      based on the known fossil record of theropod dinosaurs and osteological
      correlates in extant birds: (1) Phase I-Elaboration of paraxial cervical air sacs
      in basal theropods no later than the earliest Late Triassic. (2) Phase II
      Differentiation of avian ventilatory air sacs, including both cranial (clavicular
      air sac) and caudal (abdominal air sac) divisions, in basal tetanurans during the
      Jurassic. A heterogeneous respiratory tract with compliant air sacs, in turn,
      suggests the presence of rigid, dorsally attached lungs with flow-through
      ventilation. (3) Phase III-Evolution of a primitive costosternal pump in
      maniraptoriform theropods before the close of the Jurassic. (4) Phase IV
      Evolution of an advanced costosternal pump in maniraptoran theropods before the
      close of the Jurassic. In addition, we conclude: (5) The advent of avian
      unidirectional lung ventilation is not possible to pinpoint, as osteological
      correlates have yet to be identified for uni- or bidirectional lung ventilation.
      (6) The origin and evolution of avian air sacs may have been driven by one or
      more of the following three factors: flow-through lung ventilation, locomotory
      balance, and/or thermal regulation.

PMID- 18825274
TI  - Radiologic evaluation of small renal masses (II): posttreatment management.
AB  - The increase in the detection of small renal masses (SRMs) and their best
      knowledge leads to a change in the therapeutic management of these lesions. The
      use of a less aggressive surgical technique or even an expectant attitude is the
      current tendency, in order to preserve as much renal function as possible.
      Imaging techniques are essential in the followup of these lesions. It allows us
      to know the postsurgical changes and possible complications due to treatment and
      the presence of local recurrence and metastases. Furthermore, a close
      radiological followup of SRM related to ablative treatments is mandatory. The
      purpose of this article is to reveal the imaging features of complications due to
      surgical or ablative treatments, local recurrence and metastasis, as well as
      their followup.

PMID- 18825275
TI  - Inducible SOS response system of DNA repair and mutagenesis in Escherichia coli.
AB  - Chromosomal DNA is exposed to continuous damage and repair. Cells contain a
      number of proteins and specific DNA repair systems that help maintain its correct
      structure. The SOS response was the first DNA repair system described in
      Escherichia coli induced upon treatment of bacteria with DNA damaging agents
      arrest DNA replication and cell division. Induction of the SOS response involves
      more than forty independent SOS genes, most of which encode proteins engaged in
      protection, repair, replication, mutagenesis and metabolism of DNA. Under normal
      growth conditions the SOS genes are expressed at a basal level, which increases
      distinctly upon induction of the SOS response. The SOS-response has been found in
      many bacterial species (e.g., Salmonella typhimurium, Caulobacter crescentus,
      Mycobacterium tuberculosis), but not in eukaryotic cells. However, species from
      all kingdoms contain some SOS-like proteins taking part in DNA repair that
      exhibit amino acid homology and enzymatic activities related to those found in E.
      coli. but are not organized in an SOS system. This paper presents a brief up-to
      date review describing the discovery of the SOS system, the physiology of SOS
      induction, methods for its determination, and the role of some SOS-induced genes.

PMID- 18825276
TI  - Significant associations of stearoyl-CoA desaturase (SCD1) gene with fat
      deposition and composition in skeletal muscle.
AB  - Gene expression studies in humans and animals have shown that elevated stearoyl
      CoA desaturase (SCD1) activity is associated with increased fat accumulation and
      monounsaturation of saturated fatty acids in skeletal muscle. However, results of
      the two reported association studies in humans are inconsistent. In the present
      study, we annotated the bovine SCD1 gene and identified 3 single nucleotide
      polymorphisms (SNPs) in its 3'untranslated region (UTR). Genotyping these SNPs on
      a Wagyu x Limousin reference population revealed that the SCD1 gene was
      significantly associated with six fat deposition and fatty acid composition
      traits in skeletal muscle, but not with subcutaneous fat depth and percent kidney
      pelvic-heart fat. In particular, we confirmed that the high stearoyl-CoA
      desaturase activities/alleles were positively correlated with beef marbling
      score, amount of monounsaturated fatty acids and conjugated linoleic acid
      content, but negatively with amount of saturated fatty acids. The inconsistent
      associations between human studies might be caused by using different sets of
      markers because we observed that most associated markers are located near the end
      of 3'UTR. We found that the proximity of the polyadenylation signal site is
      highly conserved among human, cattle and pig, indicating that the region might
      contain functional elements involved in posttranscriptional control of SCD1
      activity. In conclusion, our cross species study provided solid evidence to
      support SCD1 gene as a critical player in skeletal muscle fat metabolism.

PMID- 18825278
TI  - Simultaneous dislocation of the radial head and distal radio-ulnar joint. A case
      report.
AB  - Isolated dislocation of the distal radio-ulnar joint and isolated dislocation of
      the radial head in adults are not common injuries. A simultaneous dislocation of
      the radial head and distal radio-ulnar joint with no other injury seems to be
      extremely rare since only one report was found in the English literature. A
      similar case, but with some differences in presentation and treatment is
      reported.

PMID- 18825277
TI  - EGFR expression in gallbladder carcinoma in North America.
AB  - BACKGROUND: Increased epidermal growth factor receptor (EGF receptor) expression
      has been noted in various cancers and has become a useful target for therapeutic
      interventions. Small studies from Asia and Australia have demonstrated EGFR over
      expression in gallbladder cancer. We sought to evaluate the expression of EGFR in
      a series of 16 gallbladder cancer patients from North America. METHODS: Using
      tumor registry data, we identified 16 patients diagnosed with gall bladder
      carcinoma at our medical center between the years of 1998 and 2005. We performed
      a retrospective review of these patients' charts, obtained cell blocks from
      pathology archives and stained for EGFR and Her2/neu. RESULTS: Fifteen of sixteen
      patients were noted to over-express EGFR. Three were determined 1+, nine were 2+
      and three were 3+. Eight patients had poorly differentiated adenocarcinoma, six
      had moderately differentiated and two had well-differentiated tumors. In this
      small series, there was a trend toward shorter survival and more poorly
      differentiated tumors in patients with greater intensity of EGFR expression. One
      patient was EGFR negative but 3+ for erb-2/Her 2-neu expression. No patient co
      expressed EGFR and Her-2-neu. Median survival of patients in this series was 17
      months. CONCLUSION: In view of our observations confirming the over-expression of
      EGFR in our patient population in North America, and the recent success of EGFR
      targeted therapies in other solid tumors that over-express EGFR, it may now be
      appropriate to evaluate agents targeting this pathway either as single agents or
      in combination with standard chemotherapy.

PMID- 18825279
TI  - Antifungal potential of extracellular metabolites produced by Streptomyces
      hygroscopicus against phytopathogenic fungi.
AB  - Indigenous actinomycetes isolated from rhizosphere soils were assessed for in
      vitro antagonism against Colletotrichum gloeosporioides and Sclerotium rolfsii. A
      potent antagonist against both plant pathogenic fungi, designated SRA14, was
      selected and identified as Streptomyces hygroscopicus. The strain SRA14 highly
      produced extracellular chitinase and beta-1,3-glucanase during the exponential
      and late exponential phases, respectively. Culture filtrates collected from the
      exponential and stationary phases inhibited the growth of both the fungi tested,
      indicating that growth suppression was due to extracellular antifungal
      metabolites present in culture filtrates. The percentage of growth inhibition by
      the stationary culture filtrate was significantly higher than that of exponential
      culture filtrate. Morphological changes such as hyphal swelling and abnormal
      shapes were observed in fungi grown on potato dextrose agar that contained the
      culture filtrates. However, the antifungal activity of exponential culture
      filtrates against both the experimental fungi was significantly reduced after
      boiling or treatment with proteinase K. There was no significant decrease in the
      percentage of fungal growth inhibition by the stationary culture filtrate that
      was treated as above. These data indicated that the antifungal potential of the
      exponential culture filtrate was mainly due to the presence of extracellular
      chitinase enzyme, whereas the antifungal activity of the stationary culture
      filtrate involved the action of unknown thermostable antifungal compound(s).

PMID- 18825280
TI  - Modelling charge transport in organic semiconductors: from quantum dynamics to
      soft matter.
AB  - The charge carrier dynamics in organic semiconductors has been traditionally
      discussed with the models used in inorganic crystalline and amorphous solids but
      this analogy has severe limitations because of the more complicated role of
      nuclear motions in organic materials. In this perspective, we discuss how a new
      approach to the modelling of charge transport is emerging from the alliance
      between the conventional quantum chemical methods and the methods more
      traditionally used in soft-matter modelling. After describing the conventional
      limit cases of charge transport we discuss the problems arising from the
      comparison of the theory with the experimental and computational results. Several
      recent applications of numerical methods based on the propagation of the
      wavefunction or kinetic Monte Carlo methods on soft semiconducting materials are
      reviewed.

PMID- 18825281
TI  - Raman spectroscopic evidence for the most stable water/ethanol dimer and for the
      negative mixing energy in cold water/ethanol trimers.
AB  - Spontaneous Raman scattering in supersonic jet expansions is used to prove that
      the mixed dimer of ethanol and water (corresponding to a volume fraction of 79%
      ethanol in the liquid) prefers ethanol in a gauche conformation as the hydrogen
      bond acceptor. This represents a particularly simple case of adaptive
      aggregation. Furthermore, it is shown experimentally that the isolated cold
      trimer built from one ethanol and two waters (corresponding to 64% ethanol in the
      liquid) has a significantly negative excess enthalpy, in line with the
      thermodynamic bulk observation at room temperature.

PMID- 18825282
TI  - Generation and detection of the cyclohexadienyl radical in phosphonium ionic
      liquids.
AB  - The formation of the cyclohexadienyl radical, C(6)H(6)Mu, in ionic and molecular
      solvents has been compared. This is the first time that a muoniated free radical
      is reported in an ionic liquid. In marked contrast to molecular liquids, free
      radical generation in ionic liquids is significantly enhanced. Comparison of the
      hyperfine interactions in the ionic liquid and in molecular solvents and with
      theoretical calculations, suggests significant and unforeseen solvent interaction
      with the cyclohexadienyl radical.

PMID- 18825283
TI  - Multiresolution stochastic simulations of reaction-diffusion processes.
AB  - Stochastic simulations of reaction-diffusion processes are used extensively for
      the modeling of complex systems in areas ranging from biology and social sciences
      to ecosystems and materials processing. These processes often exhibit disparate
      scales that render their simulation prohibitive even for massive computational
      resources. The problem is resolved by introducing a novel stochastic
      multiresolution method that enables the efficient simulation of reaction
      diffusion processes as modeled by many-particle systems. The proposed method
      quantifies and efficiently handles the associated stiffness in simulating the
      system dynamics and its computational efficiency and accuracy are demonstrated in
      simulations of a model problem described by the Fisher-Kolmogorov equation. The
      method is general and can be applied to other many-particle models of physical
      processes.

PMID- 18825284
TI  - Prediction of non-ideal behavior of polarity/polarizability scales of solvent
      mixtures by integration of a novel COSMO-RS molecular descriptor and neural
      networks.
AB  - A new COSMO-RS descriptor (S(sigma-profile)) has been used in quantitative
      structure-property relationship (QSPR) studies based on neural networks (NN) for
      the prediction of polarity/polarizability scales of pure solvents and mixtures.
      S(sigma-profile) is a two-dimensional quantum chemical parameter which quantifies
      the polar electronic charge on the polarity (sigma) scale. Firstly, radial base
      neural networks (RBNN) are successfully optimized for the prediction of
      polarizability (SP) and polarity/polarizability (SPP) scales of pure solvents
      using the S(sigma-profile) of individual molecules. Subsequently, based on the
      additive character of the S(sigma-profile) parameter, we propose to simulate the
      solvents mixture by the estimation of S descriptor, defined as the weighted mean
      of S(sigma-profile) values of the components. Then, the SPP parameters for binary
      and ternary mixtures are accurately predicted using the S values into the RBNN
      model previously developed for pure solvents. As result, we obtain a unique
      neural network tool to simulate, with similar reliability, the
      polarity/polarizability of a wide variety of pure organic solvents as well as
      binary and ternary mixtures which exhibit significant deviations from ideality.

PMID- 18825285
TI  - Difference for SO2 and CO2 in TGML ionic liquids: a theoretical investigation.
AB  - Quantum chemical calculations (QM) have been used to investigate the interaction
      between sulfur dioxide (SO(2)) or carbon dioxide (CO(2)) molecules and ions of
      1,1,3,3-tetramethylguanidium (TMG) lactate (LAC) (TMGL) ionic liquid. The QM
      results give us a deeper understanding of the factors that govern the high
      solubility of SO(2) in TMGL and the difference in the solubility of SO(2) and
      CO(2) in TMGL. The predicted geometries and binding energies imply a strong
      organization of SO(2) about the TMGL components, especially the LAC anion; but
      indicate a relatively weak organization of CO(2). Both the SO(2) and CO(2)
      molecules can interact with the TMG cations forming a N-H...O interaction;
      however, the binding energies demonstrate that the interaction with CO(2) is
      weaker than that with SO(2). The theoretical results indicate that the oxygen
      atoms of the LAC anion are the main active sites for the absorption of SO(2).
      Strong SO interactions are found for both the SO(2)-LAC and SO(2)-TMGL complexes.

PMID- 18825286
TI  - Effect of palladium on the reducibility of Mn based materials: correlation with
      methane oxidation activity.
AB  - Mn-based oxide supports were synthesized using different procedures: (i)
      carbonate co-precipitation method, leading to the formation of a hexaaluminate
      crystallized solid (La(0.2)Sr(0.3)Ba(0.5)MnAl(11)O(19)) and (ii) solid-solid
      diffusion method, leading to the formation of a doped theta-Al(2)O(3)
      crystallized solid (nominal composition: 60 wt%
      La(0.2)Sr(0.3)Ba(0.5)MnAl(11)O(19) + 40 wt% Al(2)O(3)). Impregnation of 1.0 wt%Pd
      was carried out on both oxides. The solids were tested for the catalytic methane
      combustion up to 700 degrees C. It was observed that adding palladium resulted in
      an important increase in the catalytic activity. The combined use of H(2)-TPR and
      XPS techniques reveals that only Mn(3+)/Mn(2+) redox "couple" is present in the
      solids, whatever the synthesis procedure used. The fraction Mn(3+)/Mn is
      proportional to the total Mn content in the solid support, whatever the sample
      structure (hexaaluminate or doped theta-Al(2)O(3)) and its morphology (large
      crystals or aggregates of small particles, respectively). Pd impregnation and
      further calcination at 650 degrees C has no significant effect on the Mn(3+)/Mn
      fraction. However, some changes in Mn(3+) reduction profile are observed,
      depending on the solid structure. Indeed, palladium addition strongly affects the
      manganese reducibility with an important shift of the reduction process to lower
      temperatures (approximately 100 degrees C). On the basis of redox properties
      observed for the different catalysts, a Mars-van-Krevelen redox mechanism, with
      oxygen transfer from support oxides to palladium particles, is proposed to
      explain the difference in terms of catalytic conversion and stability with
      respect to a 1.0 wt%Pd/Al(2)O(3) reference sample.

PMID- 18825287
TI  - The intermolecular potential in NO-N2 and (NO-N2)+ systems: implications for the
      neutralization of ionic molecular aggregates.
AB  - The characterization of the non covalent interaction potential, responsible for
      the intermolecular bond in NO-N(2) and (NO-N(2))(+) molecular aggregates, has
      been achieved by coupling the predictions of a semiempirical method with the
      results of a scattering experiment and ab initio calculations. The potential
      wells for the most stable configurations of the neutral and ionic state, having
      approximatively a T shape in both cases, fall in the same intermolecular distance
      range. In addition, in the ionic state, the charge is completely localized on the
      NO partner. Important implications on the dynamics of the neutralization process,
      occurring as a vertical transition from ionic to neutral state, are obtained by
      exploiting the analytical formulation of the interaction and calculating energy
      spacings and relevant Franck-Condon factors for both intramolecular and
      intermolecular vibration modes.

PMID- 18825288
TI  - A molecular dynamics study of the effects of the inclusion of dopants on ablation
      in polymethyl methacrylate.
AB  - Molecular dynamics simulations are used to elucidate mechanisms of ablation in
      dopant-polymer systems. In one set of simulations, a uniform distribution of
      thermal absorbers are added to a polymethyl methacrylate substrate and are
      excited. Chemical decomposition occurs in the regions near the absorbers.
      Ejection of large pieces of substrate then follows the thermo-chemical breakdown
      of material. In another set of simulations, an absorbing cluster is embedded in
      the polymethyl methacrylate substrate at a depth of 50 or 250 A. Only the
      particles comprising the cluster are excited during the laser pulse. Ejection of
      material is initiated upon the fracture of the cluster and the cleavage of the
      surrounding polymer bonds with little chemical damage during the process. These
      two mechanisms of ejection suggest different pathways of ablation in doped
      polymer materials.

PMID- 18825289
TI  - A first-principles investigation of the effect of Pt cluster size on CO and NO
      oxidation intermediates and energetics.
AB  - As catalysis research strives toward designing structurally and functionally well
      defined catalytic centers containing as few active metal atoms as possible, the
      importance of understanding the reactivity of small metal clusters, and in
      particular of systematic comparisons of reaction types and cluster sizes, has
      grown concomitantly. Here we report density functional theory calculations (GGA
      PW91) that probe the relationship between particle size, intermediate structures,
      and energetics of CO and NO oxidation by molecular and atomic oxygen on Pt(x)
      clusters (x = 1-5 and 10). The preferred structures, charge distributions,
      vibrational spectra, and energetics are systematically examined for oxygen (O(2),
      2O, and O), CO, CO(2), NO, and NO(2), for CO/NO co-adsorbed with O(2), 2O, and O,
      and for CO(2)/NO(2) co-adsorbed with O. The binding energies of oxygen, CO, NO,
      and of the oxidation products CO(2) and NO(2) are all markedly enhanced on Pt(x)
      compared to Pt(111), and they trend toward the Pt(111) levels as cluster size
      increases. Because of the strong interaction of both the reactants and products
      with the Pt(x) clusters, deep energy sinks develop on the potential energy
      surfaces of the respective oxidation processes, indicating worse reaction
      energetics than on Pt(111). Thus the smallest Pt clusters are less effective for
      catalyzing CO and NO oxidation in their original state than bulk Pt. Our results
      further suggests that oxidation by molecular O(2) is thermodynamically more
      favourable than by atomic O on Pt(x). Conditions and applications in which the
      Pt(x) clusters may be effective catalysts are discussed.

PMID- 18825290
TI  - Complexes of HNO3 and NO3 - with NO2 and N2O4, and their potential role in
      atmospheric HONO formation.
AB  - Calculations were performed to determine the structures, energetics, and
      spectroscopy of the atmospherically relevant complexes (HNO(3)).(NO(2)),
      (HNO(3)).(N(2)O(4)), (NO(3)(-)).(NO(2)), and (NO(3)(-)).(N(2)O(4)). The binding
      energies indicate that three of the four complexes are quite stable, with the
      most stable (NO(3)(-)).(N(2)O(4)) possessing binding energy of almost -14 kcal
      mol(-1). Vibrational frequencies were calculated for use in detecting the
      complexes by infrared and Raman spectroscopy. An ATR-FTIR experiment showed
      features at 1632 and 1602 cm(-1) that are attributed to NO(2) complexed to NO(3)(
      ) and HNO(3), respectively. The electronic states of (HNO(3)).(N(2)O(4)) and
      (NO(3)(-)).(N(2)O(4)) were investigated using an excited state method and it was
      determined that both complexes possess one low-lying excited state that is
      accessible through absorption of visible radiation. Evidence for the existence of
      (NO(3)(-)).(N(2)O(4)) was obtained from UV/vis absorption spectra of N(2)O(4) in
      concentrated HNO(3), which show a band at 320 nm that is blue shifted by 20 nm
      relative to what is observed for N(2)O(4) dissolved in organic solvents. Finally,
      hydrogen transfer reactions within the (HNO(3)).(NO(2)) and (HNO(3)).(N(2)O(4))
      complexes leading to the formation of HONO, were investigated. In both systems
      the calculated potential profiles rule out a thermal mechanism, but indicate the
      reaction could take place following the absorption of visible radiation. We
      propose that these complexes are potentially important in the thermal and
      photochemical production of HONO observed in previous laboratory and field
      studies.

PMID- 18825291
TI  - Segmental order parameters in a nonionic surfactant lamellar phase studied with
      1H-13C solid-state NMR.
AB  - A lyotropic nonionic lamellar system composed of pentaethyleneglycol mono n
      dodecyl ether and D(2)O was studied using natural abundance (13)C NMR under magic
      angle spinning. Applying a two-dimensional recoupling method proposed by
      Dvinskikh (R-PDLF), (1)H-(13)C dipolar couplings were estimated over a range of
      temperatures (300-335 K), thus enabling analysis of structural changes in the
      liquid crystalline system. The results obtained are used to correlate the
      conformation and mobility of local sites in the surfactant molecule with overall
      changes in the lamellar structure.

PMID- 18825292
TI  - Melting and freezing of water in cylindrical silica nanopores.
AB  - Freezing and melting of H(2)O and D(2)O in the cylindrical pores of well
      characterized MCM-41 silica materials (pore diameters from 2.5 to 4.4 nm) was
      studied by differential scanning calorimetry (DSC) and (1)H NMR cryoporometry.
      Well-resolved DSC melting and freezing peaks were obtained for pore diameters
      down to 3.0 nm, but not in 2.5 nm pores. The pore size dependence of the melting
      point depression DeltaT(m) can be represented by the Gibbs-Thomson equation when
      the existence of a layer of nonfreezing water at the pore walls is taken into
      account. The DSC measurements also show that the hysteresis connected with the
      phase transition, and the melting enthalpy of water in the pores, both vanish
      near a pore diameter D* approximately equal to 2.8 nm. It is concluded that D*
      represents a lower limit for first-order melting/freezing in the pores. The NMR
      spin echo measurements show that a transition from low to high mobility of water
      molecules takes place in all MCM-41 materials, including the one with 2.5 nm
      pores, but the transition revealed by NMR occurs at a higher temperature than
      indicated by the DSC melting peaks. The disagreement between the NMR and DSC
      transition temperatures becomes more pronounced as the pore size decreases. This
      is attributed to the fact that with decreasing pore size an increasing fraction
      of the water molecules is situated in the first and second molecular layers next
      to the pore wall, and these molecules have slower dynamics than the molecules in
      the core of the pore.

PMID- 18825293
TI  - Coadsorbed H and CO interaction on platinum.
AB  - The behavior of hydrogen near a platinum-surface-adsorbed carbon monoxide
      molecule is described using a potential energy term constructed from density
      functional theory. A clear nonattractive interaction of hydrogen with CO is
      confirmed, most notably with oxygen, which retains its strong H-repulsive traits
      in the Pt-bound CO case. Inhibiting effects of CO greater than what is expected
      from simple adsorption site exclusion are discussed with regard to
      adsorption/desorption and mobility on platinum, as well as possibilities of COH
      and HCO formation.

PMID- 18825294
TI  - Anhydrous proton-conducting properties of triazole-phosphonic acid copolymers: a
      combined study with MAS NMR.
AB  - The synthesis, thermal and proton conducting properties of copolymers based on
      vinylphosphonic acid (VPA) and 1-vinyl-1,2,4-triazole (VTri) were investigated.
      The copolymers were synthesized by free-radical copolymerization of the
      corresponding monomers at several monomer feed ratios to obtain poly(VPA-co-VTri)
      copolymer electrolytes. The final structures of the copolymers were confirmed by
      spectroscopic methods. The composition of the low molecular weight copolymers was
      varied with the feed ratio of the monomers. The presence of triazole units in the
      copolymers suppresses the formation of phosphonic acid anhydrides up to 150
      degrees C, as verified by both (31)P NMR and TGA. The observation of defined
      glass transition temperatures indicated that the ionic interactions do not
      prevent segmental relaxations of the polymer chains. In the absence of humidity,
      the copolymer electrolyte, poly(VPA-co-VTri), S2 (with 33% triazole content)
      showed proton conductivity of 10(-3) S cm(-1) at 120 degrees C, which is far
      higher than in imidazole based copolymers. Two different types of hydrogen-bonded
      protons were detected by (1)H MAS NMR in the solid copolymer systems, due to
      different arrangements of triazole and phosphonic acid units.

PMID- 18825295
TI  - [Systemic therapy of metastasizing renal cell carcinoma].
AB  - Once surgical options have been exhausted, systemic therapy is indicated for
      metastasizing renal cell carcinoma. Until recently this was carried out using
      mainly immunotherapeutic concepts with unsatisfactory results. Since the majority
      of clear cell renal cell carcinomas are well vascularised, angiogenetic
      inhibition offered an alternative therapy goal. To date, four substances have
      been approved to control angiogenesis in the therapy of renal cell carcinoma:
      sunitinib, sorafenib, temsirolimus, as well as a combination of bevacizumab and
      interferon alpha. Other substances, such as everolimus, pazopanib and axitinib,
      are currently the subject of clinical trials. Initial data on tolerance and
      efficacy was presented at this years annual conference of the American Society of
      Clinical Oncology (ASCO). This article examines current therapy options and ASCO
      data and discusses future trends.

PMID- 18825299
TI  - Organochlorine pesticide and polychlorinated biphenyl in calves from north-west
      Spain.
AB  - The aim of the present study was to assess the levels of organic pollutants in
      cattle from the NW of Spain. The livers of 101 animals from two regions (Galicia
      and Asturias) were analysed for seven organochlorine pesticides (HCB, alpha-HCCH,
      u-HCCH, HEOD, DDT, TDE) and 34 PCBs congeners (8, 18, 28, 29, 31, 52, 77, 101,
      105, 114, 118, 123, 126, 128, 138, 141, 149, 153, 156, 157, 167, 169, 170, 171,
      180, 183, 187, 189, 194, 199, 201, 205, 206 and 209). The influence of different
      factors (type of farm and proximity to industrial areas) on pesticide
      accumulation in cattle was also studied. Overall, the frequency of occurrence and
      concentrations of OC pesticides and PCBs was low in calves from both regions.
      HEOD was detected most frequently and was found in more than half of the calves
      from each region. PCBs 141 and 153 were the most frequently detected PCB
      congeners but typically occurred in less than 20% of animals. The exposure of
      calves to the more abundant contaminants differed significantly between the
      regions and may be related to past usage patterns. Differences between farms in
      terms of their livestock management did not have a significant effect on
      pesticide accumulation by calves. The liver concentrations in calves were below
      maximum residues levels (RMLs) for human intake and there is no indication of any
      risk from these contaminants through eating calf liver.

PMID- 18825300
TI  - High prevalence of vitamin K and D deficiency and decreased BMD in inflammatory
      bowel disease.
AB  - SUMMARY: Vitamin K and D deficiency and decreased bone mineral density (BMD) were
      highly prevalent in patients with inflammatory bowel disease (IBD), especially
      Crohn's disease (CD). Dietary intakes of these vitamins, however, were above the
      Japanese adequate intakes in IBD patients, suggesting that malabsorption is the
      basis for hypovitaminosis K and D and decreased BMD. INTRODUCTION: We have
      studied the possible involvement of vitamin K and D deficiency in the
      pathogenesis of decreased BMD in IBD. METHODS: Seventy patients with IBD were
      evaluated for their BMD; plasma levels of vitamin K; phylloquinone (PK),
      menaquinone-7 (MK-7), and 25OH-D; serum PTH, protein induced by vitamin K absence
      (PIVKA-II), and undercarboxylated osteocalcin (ucOC) levels; and their food
      intake. RESULTS: Compared with ulcerative colitis (UC) patients, CD patients had
      significantly lower plasma vitamin K and 25OH-D concentrations; significantly
      higher serum levels of PTH, PIVKA-II, and ucOC; and significantly lower BMD
      scores at almost all measurement sites. More IBD patients were vitamin K
      deficient in bone than in liver. Multiple regression analyses revealed that low
      plasma concentrations of vitamin K and 25OH-D were independent risk factors for
      low BMD and that they were associated with the patients' fat intake, but not with
      their intake of these vitamins. CONCLUSION: IBD patients have high prevalence of
      decreased BMD and vitamin K and D deficiency probably caused by malabsorption of
      these vitamins.

PMID- 18825301
TI  - Connections between the accessory nerve and the posterior root of the first
      cervical nerve.
AB  - The aim of this study was to demonstrate the incidence of absence of the
      posterior root of the first cervical nerve, and the relation between the
      accessory nerve and the posterior root of the first cervical nerve in Turkish
      population. Dissections of the accessory nerve and the posterior root of the
      first cervical nerve were performed in 49 specimens from 27 formalin fixed
      cadavers (25 male and 2 female). The type of the connections between the
      accessory nerve and the posterior root of the first cervical nerve was classified
      into four types. Type III was the most common type in present study (30.6%).
      There was a connection between the accessory nerve and the posterior root of the
      first cervical nerve in this type. The connections demonstrated in this study are
      important in the etiology and surgical treatment of the spasmodic torticollis.

PMID- 18825302
TI  - Repaglinide plus single-dose insulin glargine: a safe regimen for low-risk type 2
      diabetic patients who insist on fasting in Ramadan.
AB  - Aim of this prospective study is to evaluate the effect of repaglinide t.i.d.
      (three times a day) plus single-dose insulin glargine regimen in low-risk type 2
      diabetic patients during Ramadan fasting. Participants had been taking the
      regimen for at least 3 months. Patients with a history of diabetic coma, severe
      hypoglycemic crisis or repeating attacks of hypoglycemia were excluded.
      Hypoglycemic unawareness, kidney or liver disease or HbA1c over 8% were also
      accepted as exclusion criteria. Eleven patients who insisted on this worship and
      eight non-fasting cases were involved. All were told to make home-glucose
      monitorisation weekly and report any hypoglycemic event throughout Ramadan.
      Fasting blood glucose (FBG), post-prandial blood glucose (PBG) and fructosamine
      levels, body weights and blood pressures were recorded just before and after
      Ramadan. Seven patients in each group concluded the follow-up. Any significant
      change was detected in the parameters in either groups (P>0.05). Glucose control
      remained unchanged; fructosamine 318.14+/-65.38 versus 317.28+/-52.80 mmol/L in
      fasting group, 290.71+/-38.48 versus 290+/-38.56 mmol/L in non-fasting group.
      None of them exhibited either a major or a minor hypoglycemic event. The results
      of this pilot study indicated that repaglinide t.i.d. plus single-dose insulin
      glargine regimen was safe for low-risk type 2 diabetic patients who insisted on
      fasting during Ramadan.

PMID- 18825303
TI  - Relapsing remitting hypnic headache responsive to indomethacin in an adolescent:
      a case report.
AB  - Hypnic headache (HH) is a rare sleep-associated primary headache disorder that
      usually begins after the age of 60 years. Here we report a 19-year-old male with
      4-year history of predominantly left sided HH. He is the youngest person reported
      who fulfills the IHS diagnostic criteria for HH. The patient had history of
      relapsing-remitting course. The headache occurred every night at a constant time
      in each relapse. It was non-throbbing, moderate to severe, for 30 min to 5 h, and
      usually after 3 h of sleep. The patient showed complete response to indomethacin
      (75 mg at bedtime). Frequent tapering of indomethacin was required to look for
      the remission phase.

PMID- 18825304
TI  - Cytotoxicity of advanced glycation endproducts in human micro- and astroglial
      cell lines depends on the degree of protein glycation.
AB  - Advanced glycation endproducts (AGEs) arise from the reaction of sugars with side
      chains and the N-terminus of proteins and are thought to be involved in the
      pathogenesis of several diseases by inducing oxidative stress, inflammation and
      cell death presumably mediated through activation of the receptor of AGE (RAGE).
      To address the question whether the cell damaging effect of AGE depends on the
      degree of its protein glycation, differential modified AGEs derived from
      incubating human serum albumin with increasing concentrations of methyl glyoxal
      were tested on cell viability, reactive oxygen species (ROS) formation,
      intracellular ATP levels, and activation of caspases 3/7 in two human glial cell
      lines, which were used as a model for human glia cells. All AGEs tested,
      regardless of their degree of modification, were found to induce ROS formation in
      both microglial (CHME-5) and astroglial cells (U373 MG), while only highly
      modified AGEs were able to decrease the cell viability and to induce apoptosis.
      This indicates that apoptotic events may be involved in the change of
      physiological parameters.

PMID- 18825305
TI  - Amino acid contacts in proteins adapted to different temperatures: hydrophobic
      interactions and surface charges play a key role.
AB  - Thermophiles, mesophiles, and psychrophiles have different amino acid frequencies
      in their proteins, probably because of the way the species adapt to very
      different temperatures in their environment. In this paper, we analyse how
      contacts between sidechains vary between homologous proteins from species that
      are adapted to different temperatures, but displaying relatively high sequence
      similarity. We investigate whether specific contacts between amino acids
      sidechains is a key factor in thermostabilisation in proteins. The dataset was
      divided into two subsets with optimal growth temperatures from 0-40 and 35-102
      degrees C. Comparison of homologues was made between low-temperature species and
      high-temperature species within each subset. We found that unspecific
      interactions like hydrophobic interactions in the core and solvent interactions
      and entropic effects at the surface, appear to be more important factors than
      specific contact types like salt bridges and aromatic clusters.

PMID- 18825306
TI  - Halomonas sediminis sp. nov., a new halophilic bacterium isolated from salt-lake
      sediment in China.
AB  - A novel Gram-negative, slightly halophilic, catalase- and oxidase-positive,
      obligately aerobic bacterium, strain YIM-C248(T), was isolated from a sediment
      sample collected from a salt-lake in the Qaidam Basin in Qinghai, north-west
      China. Cells were non-sporulating short rods, occurring singly or as doublets,
      motile with peritrichous flagella. Growth occurred with 1-15% (w/v) NaCl [optimum
      2-4% (w/v) NaCl], at pH 6.0-10.0 (optimum pH 7.5) and at 4-35 degrees C (optimum
      25-30 degrees C). The major cellular fatty acids were C(18:1) omega 7c, C(12:0) 3
      OH, cyclo C(19:0) omega 8c, C(16:0) and C(16:1). The predominant respiratory
      quinone was Q-9 and the genomic DNA G + C content was 58.6 mol%. Phylogenetic
      analysis based on 16S rRNA gene sequences indicated that strain YIM-C248(T)
      should be assigned to the genus Halomonas. The sequence similarities between the
      isolate and the type strains of members of the genus Halomonas were in the range
      of 92.5-97.5%. The combination of phylogenetic analysis, DNA-DNA hybridization
      data, phenotypic characteristics and chemotaxonomic differences supported the
      view that strain YIM-C248(T) represents a new species of the genus Halomonas, for
      which the name Halomonas sediminis sp. nov. is proposed, with YIM-C248(T) (=CCTCC
      AA 207031 = KCTC 22167) as the type strain.

PMID- 18825307
TI  - Predicting lymph node metastases in early gastric cancer: radical resection or
      organ-sparing therapy?

PMID- 18825308
TI  - Predicting lymph node status in early gastric cancer.
AB  - Accurate prediction of lymph node (LN) status is of crucial importance for
      appropriate treatment planning in patients with early gastric cancer (EGC).
      However, there is no definitive consensus yet on which patient and/or tumor
      characteristics are associated with LN metastasis. A systematic search for
      studies investigating the relationship between patient and/or tumor
      characteristics and LN metastasis in EGC was performed in PubMed/MEDLINE. Patient
      and/or tumor characteristics associated with LN metastasis were identified by
      meta-analyzing results of individual studies. Forty-five studies were included.
      Variables significantly associated with LN metastasis in gastric cancer limited
      to the mucosa were: age younger than 57 years, tumor location in the middle part
      of the stomach, larger tumor size, macroscopically depressed tumor type, tumor
      ulcerations, undifferentiated tumors, diffuse tumor type according to the Lauren
      classification, lymphatic tumor invasion, tumors with a proliferating cell
      nuclear antigen (PCNA) labeling index of more than 25%, and matrix
      metalloproteinase-9-positive tumors. Variables significantly associated with LN
      metastasis in gastric cancer limited to the submucosa were: female sex, tumor
      location in the lower part of the stomach, larger tumor size, undifferentiated
      tumors, increasing depth of submucosal invasion, lymphatic tumor invasion,
      vascular tumor invasion, increased submucosal vascularity, tumors with a PCNA
      labeling index of more than 25%, tumors with a gastric mucin phenotype, and
      vascular endothelial growth factor-C-positive tumors. We identified several
      variables associated with LN metastasis in EGC. These variables should be
      included in future research, in order to assess which of these variables remain
      as significant predictors of LN metastasis.

PMID- 18825309
TI  - Cadherin-catenin adhesion system and mucin expression: a comparison between young
      and older patients with gastric carcinoma.
AB  - BACKGROUND: Young patients are thought to develop gastric carcinomas with a
      molecular genetic profile that is distinct from that of gastric carcinomas
      occurring at a later age. The aim of this study was to compare the
      clinicopathological features and expression patterns of the markers E-cadherin
      and beta-catenin, and mucins (MUC1, MUC2, MUC5AC, and MUC6) in young and older
      patients. METHODS: The clinicopathological features and overall survival data of
      62 young patients (age <or=40 years) with gastric cancer were retrospectively
      reviewed from hospital records and compared with the data for 453 older patients
      (age >40 years). A tissue microarray method and immunohistochemistry were used in
      order to analyze marker expression in paraffin-embedded tissue blocks obtained
      from both groups. RESULTS: The young group presented a higher percentage of
      diffuse-type tumors in comparison to the older group (P<0.01). The rates of
      positivity for E-cadherin and beta-catenin membranous expression patterns and
      mucin (MUC2, MUC5AC and MUC6) positivity were higher in the young group (P<0.01).
      Although young patients showed a lower frequency of alterations in marker
      expression and had significantly better survival rates than the older patients,
      neither age nor the marker expression pattern were found to be independent
      prognostic factors of survival. Only stage, tumor size, and tumor location
      persisted as prognostic factors for patients with gastric cancer. CONCLUSION:
      Biological markers of cellular adhesion and gastric differentiation were
      differently expressed in young and older patients. Our findings support the
      hypothesis that young patients develop carcinomas with a different genetic
      pathway compared to the pathway of tumors occurring at a later age, and we
      suggest further investigations to assess the prognostic relevance of the markers
      to specific subgroups.

PMID- 18825310
TI  - Prognostic value of extracapsular invasion and fibrotic focus in single lymph
      node metastasis of gastric cancer.
AB  - BACKGROUND: Histological findings of metastatic lymph nodes are important
      prognosticators in patients with gastric cancer. The aim of this study was to
      clarify the clinical significance of various pathological characteristics of the
      early phase of lymph node metastasis in patients with gastric cancer, by
      selecting patients with tumors that had single lymph node metastases, no serosal
      invasion, and no metastases to the peritoneum, liver, or distant organs. METHODS:
      Seventy-eight patients were eligible and were entered in this study. These
      patients were subdivided according to the following histological characteristics
      of the one metastatic lymph node: size of the metastasis (i.e., amount of tumor
      cells [AT]), proliferating pattern (PP), intranodal location (IL), and the
      presence or absence of extracapsular invasion (ECI) and/or fibrotic focus (FF).
      Associations between clinicopathological factors, survival, and the nodal
      findings were examined. RESULTS: There were no correlations between AT or PP and
      any clinicopathological factors. IL was significantly correlated with venous
      invasion and the pathological characteristics of the primary tumor. ECI and FF
      were observed significantly more frequently in pT2 than in pT1 cancer. Overall
      survival (OS) differed significantly according to depth of invasion, venous
      invasion, and the presence or absence of ECI or FF, although OS was not affected
      by AT, PP, or IL. The 10-year overall survival rates of patients with and without
      ECI were 50% and 80%, respectively, while these rates for patients with and
      without FF were 50% and 79%, respectively. Multivariate analysis revealed that
      ECI and FF were significant prognosticators of survival. CONCLUSION: These
      results strongly suggested that the presence of ECI or FF could affect the
      survival of patients with gastric cancer.

PMID- 18825311
TI  - Endogenous estrogen exposure in relation to distribution of histological type and
      estrogen receptors in gastric adenocarcinoma.
AB  - BACKGROUND: Estrogen might protect women against gastric adenocarcinoma of the
      intestinal histological type. We addressed this hypothesis and proposed that
      gastric estrogen receptors (ERs) are involved. METHODS: A population-based cohort
      of patients with gastric adenocarcinoma diagnosed in 1958-2004 in the county of
      Stockholm was identified through the Swedish Cancer Register. The patients were
      categorized regarding their endogenous estrogen exposure at diagnosis into: women
      aged less than 50 years, labelled "exposed women" (n=364), men aged less than 50
      years, labelled "unexposed men" (n=396), and women aged more than 70 years,
      labelled "unexposed women" (n=3008). Tumor specimens were reviewed, and 289 cases
      were classified into intestinal (n=101) or diffuse type (n=188). Cases of
      intestinal adenocarcinomas (n=45) were tested for presence of ERalpha, ERbeta,
      and ERbeta cx by immunohistochemistry. RESULTS: Compared to "exposed women", the
      intestinal type of gastric adenocarcinoma was more than four times more common
      among "unexposed men" (odds ratio [OR], 4.7; 95% confidence interval [CI], 2.2
      10.3) and nine times more common among "unexposed women" (OR, 9.1; 95% CI, 4.3
      19.6). No differences in ER expression were found. A comparison of ERs in tissues
      taken from the tumors and adjacent gastric mucosa revealed a loss of ERbeta and a
      gain of ERalpha in the tumor cells. The presence of ERbeta cx was identified for
      the first time in gastric tumors. CONCLUSION: Gastric adenocarcinoma of the
      intestinal type is less common in women with high endogenous estrogen exposure,
      indicating a preventive effect of estrogen. No differences in the distribution of
      ERs was found between the three estrogen exposure groups. The presence of ERbeta
      cx in gastric cancer warrants further investigation.

PMID- 18825312
TI  - Curability of laparoscopic gastrectomy for gastric cancer: an analysis of 10
      years' experience.
AB  - BACKGROUND: Laparoscopic gastrectomy is becoming widely used for the management
      of gastric cancer. To evaluate its oncologic feasibility, we analyzed the
      curability of laparoscopic gastrectomy based on our 10-year experience. METHODS:
      All laparoscopic gastrectomies for gastric cancer performed in the past 10 years,
      with the exception of those converted to open surgery, were evaluated. The number
      of dissected lymph nodes and the proximal and distal distances between the
      primary lesion and resection lines were analyzed and compared among different
      procedures. Laparoscopic and open D2 resection were also compared. RESULTS: Most
      of the 391 eligible patients fulfilled the oncologic requirement of current
      treatment guidelines. The mean proximal and distal distances were 3.73+/-2.11 cm
      and 5.31+/-3.26 cm, respectively. A distance of less than 1 cm occurred in only
      10 patients proximally and 5 patients distally, with pathological examination
      results being negative. In each operation, an average of 22 lymph nodes were
      dissected (21.7+/-12.1). Laparoscopic D2 resection possessed the same capacity as
      open surgery in terms of lymph node dissection. The proximal distance in open
      surgery was about 1 cm longer than that in laparoscopic gastrectomy (4.99+/-2.59
      cm vs 4.06 +/- 1.87 cm; P=0.038), while the difference between distal distances
      was not significant (6.94+/-3.52 cm vs 7.24+/-4.64 cm; P=0.187). CONCLUSION: From
      the point of view of curability, laparoscopic operation is an oncologically safe
      procedure for the management of gastric cancer, at least for stage I and II
      disease.

PMID- 18825313
TI  - "Tornado Roux-en-Y" anastomosis in laparoscopy-assisted distal gastrectomy.
AB  - The use of laparoscopy-assisted distal gastrectomy has been gradually spreading
      and it has become one of the standard treatment options for early gastric cancer
      in Japan. But anastomotic problems are still frequent with this procedure,
      because of its technical difficulty. We have developed a simple, safe, and speedy
      Roux-en-Y anastomosis for use in laparoscopy-assisted distal gastrectomy. Here,
      we describe our technique and the short-term results.

PMID- 18825314
TI  - Screening of amide analogues of Trichostatin A in cultures of primary rat
      hepatocytes: search for potent and safe HDAC inhibitors.
AB  - The vast majority of preclinical studies of HDAC inhibitors (HDAC-I) focus on the
      drug-target (cancer) cell interaction, whereas little attention is paid to the
      effects on non-target healthy cells, which could provide decisive information to
      eliminate potential cytotoxic compounds at a very early stage during drug
      development. In the current study we used cultures of primary rat hepatocytes as
      a read out system to select for the most potent HDAC-I in the group of structural
      analogues of an archetypal HDAC-I, namely Trichostatin A. This kind of approach
      allowed selecting compounds with high biological activity and with no apparent
      toxicity towards cultured hepatocytes.

PMID- 18825315
TI  - Inhibition of invasion-associated thromboxane synthase sensitizes experimental
      gliomas to gamma-radiation.
AB  - The invasion- and apoptosis-associated thromboxane synthase gene encoding an
      enzyme of the arachidonic acid pathway has been implicated in glioma progression.
      Furegrelate, a specific inhibitor of thromboxane synthase, blocks cell motility,
      induces apoptosis and increases sensitivity to drug induced apoptosis in human
      glioma cells in vitro. The impact of furegrelate on the sensitivity of human
      glioma cells to gamma-irradiation was analyzed using colony formation assay in
      vitro and an orthotopic mouse model in vivo. Pre-treatment of glioma cells with
      furegrelate increases radiation sensitivity of cultured glioma cells. Treatment
      of experimental gliomas with suboptimal doses of radiation and furegrelate
      results in a significant decrease in tumor volumes compared to untreated
      controls. Thus, the specific thromboxane synthase inhibitor furegrelate increases
      death response induced by gamma-radiation in glioma cells in vitro and sensitizes
      experimental gliomas to radiation treatment in vivo.

PMID- 18825316
TI  - Possible role of single-voxel (1)H-MRS in differential diagnosis of suprasellar
      tumors.
AB  - The objective of the present study was investigation of the possible role of
      proton magnetic resonance spectroscopy ((1)H-MRS) for differential diagnosis of
      suprasellar tumors. Forty patients (23 men and 17 women; median age, 45 years)
      with suprasellar, hypothalamic, and third ventricle neoplasms underwent long-echo
      (TR: 2000 ms, TE: 136 ms, 128-256 acquisitions) single-voxel (1)H-MRS before
      surgical treatment. The volume of the voxel was either 3.4 cc or 8 cc.
      Spectroscopic data were analyzed by calculation of the various metabolite ratios
      as well as by determination of the type of the pathological (1)H-MR spectra.
      There were 19 pituitary adenomas, 7 gliomas, 5 craniopharyngiomas, 3 chordomas,
      meningioma, hemangiopericytoma, malignant lymphoma, germinoma, Rathke cleft cyst,
      and hypothalamic hamartoma (one of each). Six tumors were recurrent after initial
      surgical resection with or without irradiation. Comparison of the individual
      metabolite ratios revealed only few subtle differences among neoplasms. In the
      same time, pattern analysis with determination of the type of the pathological
      (1)H-MR spectra disclosed certain specific characteristics, which seemingly can
      be used for tumor typing. Meanwhile, metabolic imaging was less effective for
      characterization of recurrent neoplasms. In conclusion, in cases of initially
      diagnosed suprasellar tumors with involvement of the hypothalamus and extension
      into the third ventricle pattern analysis of the single-voxel (1)H-MRS can
      provide valuable information, which, in addition to structural MRI, can be
      effectively used for diagnostic purposes.

PMID- 18825317
TI  - Intravitreal bevacizumab injection in patients with choroidal neovascularization
      due to choroid rupture after blunt-head trauma.
AB  - PURPOSE: To describe and report the effect of intravitreal bevacizumab (Avastin)
      as primary treatment for secondary choroidal neovascularization (CNV) after
      choroidal rupture due to blunt-head trauma. DESIGN: Interventional case report.
      METHODS: The study was of the left eye of a patient who presented with choroidal
      neovascularization secondary to choroidal rupture due to blunt-head trauma. The
      patient received single intravitreal injection of 1.25 mg (0.05 ml) bevacizumab
      as treatment for CNV after informed consent was signed. The patient underwent
      fundus fluorescein angiography (FA) and optic coherence tomography (OCT) before
      the bevacizumab injection and then again three months after. Visual acuity was
      also measured before and after treatment. The patient was re-examined on the
      first day, and monthly thereafter. After intravitreal injection of bevacizumab
      the visual and anatomic responses were observed. RESULTS: The patient showed
      regression of the neovascularization three months after injection of bevacizumab.
      There was no loss of vision in the immediate postoperative period and at the 3rd
      month vision improved from 20/60 to 20/20. Central retinal thickness decreased.
      No cataract progression, endophthalmitis, or injection-related complications were
      observed. CONCLUSIONS: Our study shows that intravitreal 1.25 mg bevacizumab can
      be an effective alternative treatment for choroidal neovascularization (CNV) due
      to choroidal rupture.

PMID- 18825318
TI  - Early effects on T lymphocyte response to iron deficiency in mice. Short
      communication.
AB  - Iron deficiency is a common nutritional disorder, affecting about 30% of the
      world population. Deficits in iron functional compartments have suppressive
      effects on the immune system. Environmental problems, age, and other nutrient
      deficiencies are some of the situations which make human studies difficult and
      warrant the use of animal models. This study aimed to investigate alterations in
      the immune system by inducing iron deficiency and promoting recuperation in a
      mouse model. Hemoglobin concentration, hematocrit, liver iron store, and flow
      cytometry analyses of cell-surface transferrin receptor (CD71) on peripheral
      blood and spleen CD4+ and CD8+ T lymphocyte were performed in the control (C) and
      the iron-deficient (ID) groups of animals at the beginning and end of the
      experiment. Hematological indices of C and ID mice were not different but the
      iron stores of ID mice were significantly reduced. Although T cell subsets were
      not altered, the percentage of T cells expressing CD71 was significantly
      increased by ID. The results suggest that iron deficiency induced by our
      experimental model would mimic the early events in the onset of anemia, where
      thymus atrophy is not enough to influence subset composition of T cells, which
      can still respond to iron deficiency by upregulating the expression of
      transferrin receptor.

PMID- 18825319
TI  - Effects of dietary Pb on accumulation, histopathology, and digestive enzyme
      activities in the digestive system of tilapia (Oreochromis niloticus).
AB  - With the increasing occurrence of dietary lead (Pb) contamination in aquatic
      environment, threat of the dietary Pb toxicity to aquatic organisms attracted
      more attention. In this study, after being exposed to dietary Pb at
      concentrations of 0, 100, 400, and 800-microg/g dry weight for 60 days, the
      groups of tilapia (Oreochromis niloticus) were sacrificed and sampled to analyze
      the effects of dietary Pb on accumulation, histopathology, and digestive enzyme
      activities in tissues of the digestive system. The results showed that the Pb
      accumulation in tissues increased with the dietary Pb concentrations. Moreover,
      Pb accumulated in sampled tissues in the following order: intestine > stomach >
      liver. By observation of liver histological sections in optical microscope,
      lesions could be detected in the Pb-contaminated groups. It was also demonstrated
      that the inhibitory effect of dietary Pb on digestive enzyme activities was
      dietary Pb concentration dependent. Different degrees of inhibition of enzyme
      activities were exhibited in sampled tissues. It was indicated that digestive
      enzyme activities in the digestive system might be considered as the potential
      biomarkers of dietary Pb contamination in tilapia.

PMID- 18825333
TI  - Cough: setting the scene.

PMID- 18825334
TI  - Cough sensors. I. Physiological and pharmacological properties of the afferent
      nerves regulating cough.
AB  - The afferent nerves regulating cough have been reasonably well defined. The
      selective effects of general anesthesia on C-fiber-dependent cough and the
      opposing effects of C-fiber subtypes in cough have led to some uncertainty about
      their regulation of this defensive reflex. But a role for C-fibers in cough seems
      almost certain, given the unique pharmacological properties of these unmyelinated
      vagal afferent nerves and the ability of many C-fiber-selective stimulants to
      evoke cough. The role of myelinated laryngeal, tracheal, and bronchial afferent
      nerve subtypes that can be activated by punctate mechanical stimuli, inhaled
      particulates, accumulated secretions, and acid has also been demonstrated. These
      "cough receptors" are distinct from the slowly and rapidly adapting
      intrapulmonary stretch receptors responding to lung inflation. Indeed,
      intrapulmonary rapidly and slowly adapting receptors and pulmonary C-fibers may
      play no role or a nonessential role in cough, or might even actively inhibit
      cough upon activation. A critical review of the studies of the afferent nerve
      subtypes most often implicated in cough is provided.

PMID- 18825335
TI  - Cough sensors. II. Transient receptor potential membrane receptors on cough
      sensors.
AB  - The transient receptor potential (TRP) family of channels is represented by at
      least six members in primary sensory neurons. These include the TRP vanilloid
      subtypes 1 (TRPV1), 2, 3, and 4, the cold and menthol receptor TRPM8, and TRPA1.
      Much interest has been directed to the study of the TRPV1, because capsaicin has
      been instrumental in discovering the unique role of a subset of primary sensory
      neurons in causing nociceptive responses, in activating reflex pathways including
      cough, and in producing neurogenic inflammation. TRPV1 is now regarded as an
      integrator of diverse sensory modalities because it undergoes marked plasticity
      and sensitization through a variety of mechanisms, including activation of G
      protein-coupled or tyrosine kinase receptors. Evidence in experimental animals
      and in patients with airway diseases indicates a marked hypersensitivity to cough
      induced by TRPV1 agonists. Recent studies with newly developed high-affinity and
      selective TRPV1 antagonists have revealed that TRPV1 inhibition reduces cough
      induced by citric acid or antigen challenge.

PMID- 18825336
TI  - Cough sensors. III. Opioid and cannabinoid receptors on vagal sensory nerves.
AB  - Cough is a persistent symptom of many inflammatory airways' diseases. Cough is
      mediated by receptors sited on sensory nerves and then through vagal afferent
      pathways, which terminate in the brainstem respiratory centre. Cough is often
      described as an unmet clinical need. Opioids are the only prescription-based
      antitussives currently available in the UK. They possess limited efficacy and
      exhibit serious unwanted side effects, such as physical dependence, sedation,
      respiratory depression and gastrointestinal symptoms. There are three classical
      opioid receptors: the mu, kappa and delta receptors. Peripheral opioid receptors
      are sited on sensory nerves innervating the airways. A greater understanding of
      the role of the peripheral and centrally sited opioid receptors is necessary to
      allow the development of targeted treatments for cough. Because of the limited
      efficacy and the side-effect profile of the opioids, potential new treatments are
      sought to alleviate cough. One class of compounds that is currently under
      examination is the cannabinoids. Like the opioids, cannabinoids have peripheral
      and centrally sited receptors and also suffer from the blight of unwanted
      centrally mediated side effects such as sedation, cognitive dysfunction,
      tachycardia and psychotropic effects. Two cannabinoid receptors have been
      identified, the CB(1) and CB(2) receptors, and their distribution varies
      throughout the peripheral and central nervous system. Encouragingly, early
      studies with these compounds suggest that it may be possible to separate their
      antitussive activity from their centrally mediated side effects, with CB(2)
      agonists showing potential as putative new treatments for cough. In this chapter,
      we describe the opioid and cannabinoid receptors, their distribution and the
      effects they mediate. Moreover, we highlight their potential advantages and
      disadvantages in the treatment of cough.

PMID- 18825337
TI  - Cough sensors. IV. Nicotinic membrane receptors on cough sensors.
AB  - Cigarette smoke is undoubtedly one of the most common inhaled irritants in the
      human respiratory tract, and invariably evokes coughing in both smokers and
      nonsmokers. Results obtained from the studies in human volunteers and from single
      fiber recording of vagal bronchopulmonary afferents in animals clearly indicate
      that nicotine is primarily responsible for the airway irritation and coughing
      caused by inhalation of cigarette smoke. Furthermore, both nicotine and
      acetylcholine can evoke inward current, membrane depolarization, and action
      potentials in isolated pulmonary sensory neurons, and these responses are blocked
      by hexamethonium. Taken together, these findings suggest that the tussive effect
      of nicotine is probably mediated through an activation of nicotinic acetylcholine
      receptors (nAChRs) expressed on the sensory terminals of cough receptors located
      in the airway mucosa. Indeed, the expressions of alpha4-alpha7 and beta2-beta4
      subunits of nAChR transcripts in pulmonary sensory neurons have lent further
      support to this conclusion. The specific subtypes of the neuronal nAChRs and
      their subunit compositions expressed on the cough sensors remain to be
      determined.

PMID- 18825338
TI  - Cough sensors. V. Pharmacological modulation of cough sensors.
AB  - Several airway afferent nerve subtypes have been implicated in coughing. These
      include bronchopulmonary C-fibers, rapidly adapting airway mechanoreceptors and
      touch-sensitive tracheal Adelta-fibers (also called cough receptors). Although
      the last two afferent nerve subtypes are primarily sensitive to mechanical
      stimuli, all can be acted upon by one or more different chemical stimuli. In this
      review we catalogue the chemical agents that stimulate and/or modulate the
      activity of the airway afferent nerves involved in cough, and describe the
      specific mechanisms involved in these effects. In addition, we describe the
      mechanisms of action of a number of chemical inhibitors of these afferent nerve
      subtypes, and attempt to relate this information to the regulation of coughing in
      health and disease.

PMID- 18825339
TI  - Peripheral mechanisms I: plasticity of peripheral pathways.
AB  - Cough plays a vital role in protecting the lower airways from inhaled irritants,
      pollutants, and infectious agents. The cough reflex exhibits remarkable
      plasticity, such that in the context of infectious or inflammatory respiratory
      diseases such as asthma, chronic bronchitis, and idiopathic pulmonary fibrosis
      the cough reflex can become dysregulated, leading to a chronic cough. A chronic,
      nonproductive (dry) cough can rob sufferers of quality of life. Plasticity of the
      cough reflex likely involves multiple intersecting pathways within the airways,
      the peripheral nerves that supply them, and the central nervous system. While
      further studies are needed to determine the presence and relevance of many of
      these specific pathways in cough associated with chronic respiratory disease, the
      last decade has yielded unprecedented insight into the molecular identity of the
      ion channels and associated proteins that initiate and conduct action potentials
      in the primary sensory nerves involved in reflexes such as cough. We now know,
      for instance, that members of the transient receptor potential superfamily of
      nonselective cation channels function as transducers that convert specific
      external stimuli into neuronal activation. We also know that certain Na+ and K+
      channels play specialized roles in regulating action potential discharge in
      irritant-sensing afferent nerves. In this chapter, we summarize the available
      information regarding factors that may modulate afferent neuron function acutely,
      via posttranslational modifications and over the longer term through neurotrophin
      dependent alterations of the transcriptional programs of adult sensory neurons.

PMID- 18825340
TI  - Peripheral mechanisms II: the pharmacology of peripherally active antitussive
      drugs.
AB  - Cough is an indispensable defensive reflex. Although generally beneficial, it is
      also a common symptom of diseases such as asthma, chronic obstructive pulmonary
      disease, upper respiratory tract infections, idiopathic pulmonary fibrosis and
      lung cancer. Cough remains a major unmet medical need and although the centrally
      acting opioids have remained the antitussive of choice for decades, they have
      many unwanted side effects. However, new research into the behaviour of airway
      sensory nerves has provided greater insight into the mechanisms of cough and new
      avenues for the discovery of novel non-opioid antitussive drugs. In this review,
      the pathophysiological mechanisms of cough and the development of novel
      antitussive drugs are reviewed.

PMID- 18825341
TI  - Central mechanisms I: plasticity of central pathways.
AB  - Cough is the most common symptom for which individuals seek medical attention and
      spend health-care dollars. Despite the burden induced by cough, the current
      treatments for cough are only partially effective. Delineating the sites and
      mechanisms in the cough central network for changes in the cough reflex could
      lead to new therapeutic strategies and drug target sites for more effective
      treatments. The first synaptic target in the CNS for the cough-related sensory
      input is the second-order neurons in the nucleus tractus solitarius (NTS); these
      neurons reorganize the primary sensory information into a coherent output. The
      NTS neurons have been shown to undergo neuroplasticity under a variety of
      conditions, such as respiratory disorders, stress, and exposures to environmental
      pollutants. The NTS contains a rich innervation of substance P immunoreactive
      nerve terminals, suggesting that substance P might be important in altered cough
      reflex response. This chapter summarizes our current findings on the role of
      substance P in enhanced cough reflex as well as the potential NTS targets for the
      action of substance P.

PMID- 18825343
TI  - Central mechanisms III: neuronal mechanisms of action of centrally acting
      antitussives using electrophysiological and neurochemical study approaches.

PMID- 18825342
TI  - Central mechanisms II: pharmacology of brainstem pathways.
AB  - Following systemic administration, centrally acting antitussive drugs are
      generally assumed to act in the brainstem to inhibit cough. However, recent work
      in humans has raised the possibility of suprapontine sites of action for cough
      suppressants. For drugs that may act in the brainstem, the specific locations,
      types of neurones affected, and receptor specificities of the compounds represent
      important issues regarding their cough-suppressant actions. Two medullary areas
      that have received the most attention regarding the actions of antitussive drugs
      are the nucleus of the tractus solitarius (NTS) and the caudal ventrolateral
      respiratory column. Studies that have implicated these two medullary areas have
      employed both microinjection and in vitro recording methods to control the
      location of action of the antitussive drugs. Other brainstem regions contain
      neurones that participate in the production of cough and could represent
      potential sites of action of antitussive drugs. These regions include the raphe
      nuclei, pontine nuclei, and rostral ventrolateral medulla. Specific receptor
      subtypes have been associated with the suppression of cough at central sites,
      including 5-HT1A, opioid (mu, kappa, and delta), GABA-B, tachykinin neurokinin-1
      (NK-1) and neurokinin-2, non-opioid (NOP-1), cannabinoid, dopaminergic, and sigma
      receptors. Aside from tachykinin NK-1 receptors in the NTS, relatively little is
      known regarding the receptor specificity of putative antitussive drugs in
      particular brainstem regions. Our understanding of the mechanisms of action of
      antitussive drugs would be significantly advanced by further work in this area.

PMID- 18825344
TI  - Central mechanisms IV: conscious control of cough and the placebo effect.
AB  - Early animal experiments on cough developed the concept that cough was an
      involuntary reflex controlled from areas in the brainstem and that cough could be
      inhibited by centrally acting medicines such as codeine. Studies on the voluntary
      control of cough, the urge to cough and the placebo effect of cough medicines
      have demonstrated that human cough is more complex than a brainstem reflex. The
      efficacy and mechanism of action of centrally acting cough medicines such as
      codeine and dextromethorphan is now in dispute, and codeine is no longer accepted
      as a gold-standard antitussive. This review puts forward a cough model that
      includes three types of cough: (1) reflex cough, caused by the presence of food
      or fluid in the airway--this type of cough is not under conscious control and can
      occur in the unconscious subject during general anaesthesia; (2) voluntary cough-
      under conscious control that is abolished with general anaesthesia; (3) cough in
      response to sensation of airway irritation--this type of cough causes an urge to
      cough that initiates voluntary cough and may only be present in the conscious
      subject. The review proposes that human cough associated with respiratory disease
      is under conscious control and is mainly related to a sensation of airway
      irritation and an urge to cough (type 3). The review discusses the summation of
      sensory input from the airway in a brainstem integrator that reaches a threshold
      to cause reflex cough. Subthreshold conditions in the cough integrator may be
      perceived as an urge to cough that is under voluntary control. The cough model
      presented in the review has implications for the development of cough medicines
      as it indicates that the older view of cough medicines acting in the brainstem
      area to inhibit the cough reflex may need to be revised to include conscious
      control of cough as an important mechanism of cough in man.

PMID- 18825345
TI  - Clinical cough I: the urge-to-cough: a respiratory sensation.
AB  - Cough is generated by a brainstem neural network. Chemical and mechanical
      stimulation of the airway can elicit a reflex cough and can elicit a cognitive
      sensation, the urge-to-cough. The sensation of an urge-to-cough is a respiratory
      related sensation. The role of the respiratory sensation of an urge-to-cough is
      to engage behavioral modulation of cough motor action. Respiratory sensations are
      elicited by a combination of modalities: central neural, chemical, and
      mechanical. Stimulation of respiratory afferents or changes in respiratory
      pattern resulting in a cognitive awareness of breathing are mediated by central
      neural processes that are the cognitive neural basis for respiratory sensations,
      including the urge-to-cough. It is proposed that the urge-to-cough is a component
      of the cough motivation-to-action system. The urge-to-cough is induced by stimuli
      that motivate subjects to protect their airway by coughing. Cough receptor
      stimulation is gated into suprapontine brain systems. In the proposed cough
      motivation system, the cough stimulus would produce an urge-to-cough which then
      matches with the cognitive desire for a response to the urge. If a cough is
      produced by the motor action system, the descending cognitive drive modulates the
      brainstem cough neural network. Receptors within the respiratory system provide
      sensory feedback indicating if the cough occurred, the motor pattern, and the
      magnitude. The limbic system uses that information to determine if the coughing
      behavior satisfied the urge. Cough is stopped if the urge-to-cough is satisfied;
      if the urge has not been satisfied then the urge-to-cough will continue to
      motivate the central nervous system. The central component within this cough
      motivation system is the intrinsic brain mechanism which can be activated to
      start the cycle for motivating a cough, the urge-to-cough. Eliciting a cognitive
      urge-to-cough is dependent on the integration of respiratory afferent activity,
      respiratory motor drive, affective state, attention, experience, and learning.

PMID- 18825346
TI  - Clinical cough II: therapeutic treatments and management of chronic cough.
AB  - Chronic cough is a common and frequently disruptive symptom which can be
      difficult to treat with currently available medicines. Asthma/eosinophilic airway
      disease and gastro-oesophageal reflux disease are most commonly associated with
      chronic cough but it may also trouble patients with chronic obstructive pulmonary
      disease, pulmonary fibrosis and lung cancer. Over the last three decades there
      have been a number of key advances in the clinical approach to cough and a number
      of international guidelines on the management of cough have been developed.
      Despite the undoubted benefit of such initiatives, more effective treatments for
      cough are urgently needed. The precise pathophysiological mechanisms of chronic
      cough are unknown but central to the process is sensitization (upregulation) of
      the cough reflex. One well-recognized clinical consequence of this hypersensitive
      state is bouts of coughing triggered by apparently trivial provocation such as
      scents and odours and changes in air temperature. The main objective of new
      treatments for cough would be to identify ways to downregulate this heightened
      cough reflex but yet preserve its crucial role in protecting the airway. The
      combined efforts of clinicians, scientists and the pharmaceutical industry offer
      most hope for such a treatment breakthrough. The aim of this chapter is to
      provide some rationale for the current treatment recommendations and to offer
      some reflections on the management of patients with chronic cough.

PMID- 18825347
TI  - Clinical cough III: measuring the cough response in the laboratory.
AB  - As interest in clinical cough research grows, measurement of cough reflex
      sensitivity will assume an increasingly important role. With proper equipment and
      meticulous attention to methodological details, cough reflex sensitivity can be
      safely, accurately, and reproducibly determined. Such precise measurement allows
      the evaluation of the effect of pharmacological or nonpharmacological
      interventions on the sensitivity of the cough reflex, or the comparison of cough
      reflex sensitivity between different subject populations. In addition to the
      method, other vital components of optimal cough challenge testing include proper
      interpretation of data and appropriate selection of study populations.

PMID- 18825348
TI  - Clinical cough IV:what is the minimal important difference for the Leicester
      Cough Questionnaire?
AB  - BACKGROUND: The Leicester Cough Questionnaire (LCQ) is a valid, reproducible,
      responsive self-reported cough-specific health status measure. It has been used
      to assess overall efficacy of treatments for cough, but its threshold for
      clinical significance, or patient importance, is unknown. The aim of this study
      was to determine the minimal important difference (MID) of the LCQ for patients
      with chronic cough; this is the smallest change in quality-of-life score
      considered to be clinically meaningful. METHODS: The LCQ MID was first estimated
      by a multidisciplinary panel of experts who reviewed two cases of chronic cough.
      It was subsequently determined using a standardized method. Fifty-two patients
      with chronic cough of more than 8 weeks' duration attending a respiratory
      outpatient clinic were recruited. Participants completed the LCQ at initial
      evaluation and repeated the LCQ with four Global Rating of Change Questionnaires
      (GRCQ) more than 2 months later. The LCQ total score ranges from 3 to 21 and from
      1 to 7 for physical, psychological and social domains; a higher score indicates a
      better health-related quality of life. The GRCQ, a 15-point scale scored between
      +7 (a great deal better) and -7 (a great deal worse), was used to record patient
      ratings of change in cough symptoms. The MID was defined as the change in LCQ
      health status corresponding to a small change in the GRCQ score. RESULTS: The
      mean (standard deviation) LCQ MID corresponding to a small change in the GRCQ
      score was 1.3 (3.2); the MIDs for domains were as follows: physical 0.2 (0.8),
      social 0.2 (1.1) and psychological 0.8 (1.5). This MID for LCQ total score was
      similar to that determined by the expert panel. The global rating of change
      scores correlated significantly with the change in LCQ total and domain scores
      (r=0.4-0.5; p<0.005). CONCLUSION: We have demonstrated that the LCQ MID is 1.3.
      The LCQ MID should aid clinicians and researchers to make meaningful
      interpretations of health-related quality-of-life data relating to chronic cough.

PMID- 18825349
TI  - Clinical cough V: complementary and alternative medicine: therapy of cough.
AB  - We review the actions of complementary and alternative medicines (CAMs) in the
      treatment of cough and of the conditions associated with it; in particular asthma
      and upper respiratory tract infections. These therapies may work (1)
      peripherally, at the sites in the airways and lungs at which cough is being
      activated, (2) in the brainstem, where the neural "cough center" is situated, or
      (3) at the cerebral cortex, where cough can be initiated, suppressed or modified
      by conscious or unconscious controls. Of the large number of trials of CAMs
      against cough, most are inadequate in design. It may be difficult to randomize
      selection. Blinding is often impossible both for the patient and the therapist,
      and adequate placebo controls may be difficult to devise. The patient can usually
      identify the "active" treatment by the taste or smell of a medicine, or from the
      approach and apparatus being used. Pure chemicals can be extracted from many of
      the herbs used as antitussives, and can be shown to be effective in randomized,
      blind, and controlled trials, but it does not follow that the herb itself, used
      in the recommended formula and shown to be antitussive, acts by this agency
      unless a placebo effect is ruled out. A few herbs are identified where the
      evidence points to a true antitussive action. Of nonherbal treatments, the few
      positive results are usually outweighed by the larger number of negative ones.
      Thus, in general, CAMs for cough are welcomed enthusiastically by the patient but
      lack sound evidence for their efficacy. Antitussive chemicals can be extracted
      from many herbs, but it is no more than a reasonable hypothesis that the herb
      itself acts through this pathway.

PMID- 18825350
TI  - Clinical cough VI: the need for new therapies for cough: disease-specific and
      symptom-related antitussives.
AB  - Cough is a common symptom that can be self-limiting or persistent. Ideally,
      treatment of the underlying cause(s) of cough with specific treatments should
      eliminate cough. This approach may not be successful if no cause can be
      established or if the treatment of the cause fails. Suppression of cough may be
      disease-specific or symptom-related. There has been a long tradition in acute
      cough usually due to upper respiratory tract infections to use symptom-related
      antitussives. In chronic cough, suppression of cough may be achieved by disease
      specific therapies, but in many patients it may be necessary to use symptomatic
      antitussives. The efficacy of some over-the-counter symptomatic antitussives is
      often no better than that of a placebo. Currently available cough suppressants
      include the centrally acting opioids such as morphine, codeine, pholcodeine, and
      dextromethorphan. Early studies reported success in reducing cough in patients
      with chronic bronchitis or chronic obstructive pulmonary disease (COPD); however,
      a carefully conducted blinded controlled study showed no effect of codeine on
      cough of COPD. Success with these cough suppressants may be achieved at high
      doses that are associated with side effects. A slow-release preparation of
      morphine has been shown to have some degree of efficacy, but this should be
      reserved for the most severe chronic cough patient, and for patients with
      terminal cancer who may also benefit from its analgesic effects. There are case
      reports of the success of centrally acting drugs such as amitriptyline,
      paroxetine, gabapentin, and carbamezepine in chronic cough. New agents derived
      from basic research such as new opioids such as nociceptin or antagonists of
      transient receptor potential vanniloid-1 may turn out to have antitussive
      effects. Efficacy of symptomatic cough suppressants must be tested in double
      blind randomized trials using validated measures of cough in patients with
      chronic cough not responding to specific treatments. Patients with chronic cough
      need effective antitussives that could be used either on demand or on a long-term
      basis.

PMID- 18825351
TI  - [Acute intoxication with isopropanol].
AB  - Isopropanol is an ingredient of commonly used industrial and household agents.
      Intoxication can occur unintentionally, in suicide attempts or by alcohol abusers
      when used as a substitute for ethanol. Symptoms involve the gastrointestinal
      tract, the central nervous system, and the cardiovascular system at higher doses.
      Mortality is especially high in patients with deep coma and marked hypotension.
      This report describes a case of life-threatening isopropanol intoxication of a
      prison inmate successfully treated by haemodialysis.

PMID- 18825352
TI  - [Ethics and monetary values. Influence of economical aspects on decision-making
      in intensive care].
AB  - Healthcare expenditure continues to grow and the demand for cost-cutting measures
      has increased. Critical care medicine is characterized by extremely high
      expenditure and thus appears to be a suitable candidate for rationing. Based on
      the hospital address book of Germany, a questionnaire consisting of 25 multiple
      choice questions was sent out to 1,000 intensive care units (ICU). The
      questionnaire was focused on obtaining information on whether and how rationing
      takes place in Germany. A total of 540 questionnaires were returned and analyzed.
      Only approximately 25% of intensive care units stated that a special budget is
      available. Approximately 59% answered that therapeutic decisions were never or
      rarely influenced by economic reasons, but in 9% economics often influenced
      decisions. Advanced age was not considered to be a reason to limit the use of
      extremely expensive medication or the use of renal replacement therapy (RRT) in
      88% of the answers. Incurable cancer was also no reason to refuse RRT (91%). For
      35% of the answers there were no contraindications for admission to intensive
      care, whereas for 35% an incurable disease was a contraindication, for 10% a non
      resuscitation order and for 84% the patients' wishes played a decisive role. Of
      the intensive care units 67% were convinced that rationing is a matter of fact in
      ICUs in Germany and 53% were of the opinion that rationing should not occur. Of
      the answers 43% considered that limiting ICU therapy would be the best when
      rationing is necessary. Rationing therapy in critical care appears to occur daily
      in German ICUs. Due to the high costs, intensive care therapy will represent a
      very important battleground in the inevitable healthcare spending limitations of
      the future. Rationing cannot be determined exclusively by ICU doctors, thus clear
      and probably unpopular decisions on this issue are expected to be announced by
      the politicians.

PMID- 18825353
TI  - [Distal pancreatectomy: radical or spleen-preserving?].
AB  - During recent years, spleen-preserving distal pancreatectomy (SPDP) has broadened
      the operative spectrum in pancreatic surgery. The rationale for spleen-preserving
      procedures comprises prevention of overwhelming postsplenectomy infection
      syndrome (OPSI) and possibly an advantage regarding reduced carcinogenesis.
      Although there are no prospective randomized trials, SPDP and distal
      pancreatectomy with splenectomy (DPSx) seem to be equivalent in terms of blood
      loss, operative time, mortality and frequency of reoperation. Concerning
      pancreatic fistulas and other major surgical complications, current data from the
      literature are conflicting. Long-term effects of SPDP, such as development of
      gastric varices due to portal hypertension, are still insufficiently
      investigated. However, SPDP should always be considered in patients with benign
      tumors of the pancreatic tail and chronic pancreatitis. Spleen-preserving distal
      pancreatectomy can also be combined with resection of the splenic vessels (DPSx
      SVx) if the blood supply of the spleen via the small gastric vessels and the
      gastro-epoploic arcade is sufficient. In the presence of malignant tumors, DPSx
      is necessary for oncological reasons.

PMID- 18825354
TI  - [Poorly differentiated neuroendocrine carcinoma of the larynx. Diagnostic
      features, treatment strategy, and prognosis].
AB  - BACKGROUND: Small cell carcinoma of the larynx is a rare, poorly differentiated
      neuroendocrine carcinoma (NEC). It is often diagnosed late, with delayed
      initiation of adequate therapy. PATIENTS AND METHODS: The data for eight patients
      were retrospectively analyzed with regard to clinical information, surveillance,
      and diagnostic and therapeutic strategies. RESULTS: The histopathologic diagnosis
      was made after a mean of 2.88+/-2.52 months after the first symptoms occurred.
      Staging and exclusion of an extralaryngeal primary was completed 1.75+/-1.7
      months after the histological diagnosis. Seventy-five percent (n=6) of the
      patients already had regional or systemic metastases. Systemic metastases were
      detected in 50% (n=4) of the patients by FDG-positron emission
      tomography/computed tomography. Primary (n=4) or postoperative (n=3)
      radiochemotherapy was performed 3.07+/-1.32 months after initial diagnosis.
      Overall survival (n=6) was 12.83 +/-3.76 months. CONCLUSION: Studies providing
      high-level evidence cannot be expected because of the low incidence of small cell
      NEC. Efficient diagnosis should be followed immediately by combined
      radiochemotherapy. As with small cell bronchial carcinoma, small cell NEC of the
      larynx should be regarded as a systemic disease and be treated in a similar way.

PMID- 18825355
TI  - Homocysteine enhances cell proliferation in hepatic myofibroblastic stellate
      cells.
AB  - Homocysteine is an intermediate in sulfur amino acid metabolism, which takes
      place mainly in the liver. Recent studies have shown that hyperhomocysteinemia in
      patients and murine models develop hepatic fibrosis. To define mechanisms
      underlying homocysteine-induced hepatic fibrosis, the effect of homocysteine on
      hepatic stellate cell (HSC) proliferation was examined. In the present study,
      homocysteine promoted proliferation in myofibroblastic HSCs. Homocysteine
      elicited a transient formation of reactive oxygen species (ROS). The initial ROS
      activated extracellular signal-regulated kinase and p38 mitogen-activated protein
      kinase, which were involved in the activation of NAD(P)H oxidases and the
      generation of more ROS. The activation of NAD(P)H oxidases resulted from
      upregulation of the expression of p22(phox) and the phosphorylation of p47(phox).
      The ROS derived from NAD(P)H oxidases activated the PI3K/Akt pathway, thus
      promoting cellular proliferation in HSCs. These findings provide a mechanistic
      explanation for the development and progression of hepatic fibrosis in
      hyperhomocysteinemia.

PMID- 18825356
TI  - Licochalcone A isolated from licorice suppresses lipopolysaccharide-stimulated
      inflammatory reactions in RAW264.7 cells and endotoxin shock in mice.
AB  - Licochalcone A (LicA), a major phenolic constituent of the licorice species
      Glycyrrhiza inflata, exhibits various biological properties, including
      chemopreventive, anti-bacterial, and anti-spasmodic activity. We report that LicA
      inhibits inflammatory reactions in macrophages and protects mice from endotoxin
      shock. Our in vitro experiments showed that LicA suppressed not only the
      generation of nitric oxide (NO) and prostaglandin (PG)E(2), but also the
      expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2
      induced by lipopolysaccharide (LPS) in RAW264.7 cells. Similarly, LicA inhibited
      the production of inflammatory cytokines induced by LPS in RAW264.7 cells,
      including IL-1 beta and IL-6. In an animal model, LicA protected BALB/c mice from
      LPS-induced endotoxin shock, possibly through inhibiting the production of
      inflammatory cytokines and NO. Collectively, LicA inhibited the production of
      inflammatory mediators and may be a potential target for treatment of various
      inflammatory diseases.

PMID- 18825357
TI  - [Firstly smaller, secondly different: radiology in children].

PMID- 18825358
TI  - [Treatment of specific complications of locally advanced prostate cancer].
AB  - Despite improved screening methods and earlier detection of prostate carcinoma,
      the complications of locally advanced disease remain a challenge for urologists.
      The spectrum of possible complications includes subvesical obstruction,
      hydronephrosis, hematuria, pain, and local invasion of adjacent organs. Urinary
      diversion, palliative transurethral resection of the prostate, and endoscopic
      diathermy are classic procedures. Urethral stenting, laser evaporation, and
      selective arterial embolization are alternate approaches for treating these
      complex cases. Cystoprostatectomy and pelvic exenteration are ultimate options
      for patients with chronic pain and debilitating local symptoms.

PMID- 18825359
TI  - Dissection of the oligogenic resistance to Cucumber mosaic virus in the melon
      accession PI 161375.
AB  - Resistance to Cucumber mosaic virus (CMV) in the exotic melon accession PI
      161375, cultivar "Sonwang Charmi" (SC) had previously been described as
      oligogenic, recessive and quantitative, with a major QTL residing in linkage
      group XII (LGXII). We have used a collection of near isogenic lines (NILs) with
      introgressions of SC into the genome of the susceptible accession Piel de Sapo
      (PS) to further characterise this resistance. Infection of NILs carrying
      introgressions on LGXII showed that only NIL SC12-1 was resistant to CMV strains
      P9 and P104.82, but not to strains M6 and TL. Further mapping of this region
      showed that the resistance, named cmv1 maps in an area of 2.2 cM, between markers
      CMN61_44 and CMN21_55. Moreover, cmv1 confers total resistance to strains P9 and
      P104.82, indicating that in these cases it is not quantitative and that cmv1 is
      sufficient to confer full resistance to these CMV strains. Candidate gene mapping
      of ten translation initiation factors in the melon genome failed to find any of
      them in the interval between markers CMN61_44 and CMN21_55. All these results
      suggest that the resistance to CMV present in SC is oligogenic, where different
      loci confer resistance to different CMV strains, but not necessarily
      quantitative, since at least one of these genes (cmv1) confers total resistance,
      similar to that of the parental SC, and does not need the contribution of other
      loci.

PMID- 18825360
TI  - Identification of candidate signaling genes including regulators of chromosome
      condensation 1 protein family differentially expressed in the soybean
      Phytophthora sojae interaction.
AB  - Stem and root rot caused by the oomycete pathogen, Phytophthora sojae, is a
      serious soybean disease. Use of Phytophthora resistance genes (Rps) in soybean
      cultivars has been very effective in controlling this pathogen. Resistance
      encoded by Rps genes is manifested through activation of defense responses. In
      order to identify candidate signaling genes involved in the expression of
      Phytophthora resistance in soybean, a cDNA library was prepared from infected
      etiolated hypocotyl tissues of a Phytophthora resistant soybean cultivar
      harvested 2 and 4 h following P. sojae inoculation. In silico subtraction of
      101,833 expressed sequence tags (ESTs) originating from unstressed cDNA libraries
      from 4,737 ESTs of this library resulted in identification of 204 genes that were
      absent in the unstressed libraries. Of the 204 identified genes, seven were P.
      sojae genes. Putative function of 91 of the 204 genes could not be assigned based
      on sequence comparison. Macroarray analyses of all 204 genes led to
      identification of 60 genes including 15 signaling-related soybean genes and three
      P. sojae genes, transcripts of which were induced twofold in P. sojae-infected
      tissues as compared to that in water controls. Eight soybean genes were down
      regulated twofold following P. sojae infection as compared to water controls.
      Differential expression of a few selected genes was confirmed by conducting
      Northern and RT-PCR analyses. We have shown that two putative regulators of
      chromosome condensation 1 (RCC1) family proteins were down-regulated in the
      incompatible interaction. This observation suggested that the nucleocytoplasmic
      transport function for trafficking protein and non-coding RNA is suppressed
      during expression of race-specific Phytophthora resistance. Characterization of a
      cDNA library generated from tissues harvested almost immediately following P.
      sojae-infection of a resistant cultivar allowed us to identify many candidate
      signaling genes that are presumably involved in regulating the expression of
      defense-related pathways for expression of Phytophthora resistance in soybean.

PMID- 18825361
TI  - Interspecies compatibility of the anther specific cell wall invertase promoters
      from Arabidopsis and tobacco for generating male sterile plants.
AB  - Histochemical GUS-staining and fluorometric analyses revealed strong tissue
      specific activities of the cell wall invertase promoters Nin88 from Nicotiana
      tabacum and AtcwINV2 from Arabidopsis thaliana that are restricted tightly to
      anthers and pollen, respectively. Both in A. thaliana and N. tabacum repression
      of invertase activity by anther specific RNA-interference turned out to be an
      efficient method to circumvent carbohydrate supply of the symplastically isolated
      pollen with subsequent strong decrease of pollen germination ability and seed
      setting. In the case of tobacco, comparable results were also obtained by
      expressing a proteinaceous invertase inhibitor, whereas this approach was less
      efficient in Arabidopis. The present study revealed that anther specific
      interference with invertase-activity in order to generate male sterile plants can
      be applied to members of the two different plant families Solanaceae (N. tabacum)
      and Brassicaceae (A. thalaina) and the strategy seems to be a general tool for
      practical application in hybrid breeding or as biological safety precautions. To
      elucidate the compatibility of the isolated promoters beyond plant families, we
      transferred the regulatory sequences into the respectively heterologous systems,
      i.e. the Nin88 promoter into Arabidopsis and the AtcwINV2 promoter into tobacco.
      The specificities of both promoters are maintained in the heterologous
      backgrounds, but their activities are strongly reduced as GUS-stainings of
      flowers and pollen revealed and fluorometrical quantification confirmed.

PMID- 18825362
TI  - Enhancement of endothelial nitric oxide synthase production reverses vascular
      dysfunction and inflammation in the hindlimbs of a rat model of diabetes.
AB  - AIMS/HYPOTHESIS: Reduced bioavailability of nitric oxide (NO) is a hallmark of
      diabetes mellitus-induced vascular complications. In the present study we
      investigated whether a pharmacological increase of endothelial NO synthase (eNOS)
      production can restore the impaired hindlimb flow in a rat model of severe
      diabetes. METHODS: A model of diabetes mellitus was induced in male Sprague
      Dawley rats by a single injection of streptozotozin. Rats were treated
      chronically with the eNOS transcription enhancer AVE3085 (10 mg [kg body weight](
      1) day(-1); p.o.) or vehicle for 48 days and compared with controls. Endothelial
      function and arterial BP were investigated in vivo using an autoperfused hindlimb
      model and TIP-catheter measurement, respectively. Protein production of eNOS,
      total and phosphorylated vasodilator-stimulated phosphoprotein (VASP) were
      assessed in their quadriceps muscle tissue, whereas cyclic GMP (cGMP)
      concentrations were assessed in blood plasma. RNA levels of intracellular and
      vascular cell adhesion molecules (ICAM-1 and VCAM-1) were measured by real-time
      PCR. RESULTS: Untreated diabetic rats showed significantly reduced quadriceps
      muscle contents of eNOS (-64%) and phosphorylated VASP (-26%) protein associated
      with impaired vascular function (maximum vasodilatation: -30%, p < 0.05) and
      enhanced production of ICAM-1 (+121%) and VCAM-1 (+156%). Chronic treatment with
      AVE3085 did not alter arterial BP or severe hyperglycaemia, but did lead to
      significantly increased production of eNOS (+95%), cGMP (+128%) and VASP
      phosphorylation (+65%) as well as to improved vascular function (+36%) associated
      with reduced production of ICAM-1 (-36%) and VCAM-1 (-58%).
      CONCLUSIONS/INTERPRETATION: In a rat model of severe diabetes, pharmacological
      enhancement of impaired eNOS production and NO-cGMP signalling by AVE3085
      restores altered hindlimb blood flow and prevents vascular inflammation.

PMID- 18825363
TI  - Insulin resistance is associated with a modest increase in inflammation in
      subcutaneous adipose tissue of moderately obese women.
AB  - AIMS/HYPOTHESIS: We have previously described differences in adipose cell size
      distribution and expression of genes related to adipocyte differentiation in
      subcutaneous abdominal fat obtained from insulin-sensitive (IS) and -resistant
      (IR) persons, matched for degree of moderate obesity. To determine whether other
      biological properties also differ between IR and IS obese individuals, we
      quantified markers of inflammatory activity in adipose tissue from overweight IR
      and IS individuals. METHODS: Subcutaneous abdominal tissue was obtained from
      moderately obese women, divided into IR (n = 14) and IS (n = 19) subgroups by
      determining their steady-state plasma glucose (SSPG) concentrations during the
      insulin suppression test. Inflammatory activity was assessed by comparing
      expression of nine relevant genes and by immunohistochemical quantification of
      CD45- and CD68-containing cells. RESULTS: SSPG concentrations were approximately
      threefold higher in IR than in IS individuals. Expression levels of CD68, EMR1,
      IL8, IL6 and MCP/CCL2 mRNAs were modestly but significantly increased (p < 0.05)
      in IR compared with IS participants. Results of immunohistochemical staining were
      consistent with gene expression data, demonstrating modest differences between IR
      and IS individuals. Crown-like structures, in which macrophages surround single
      adipocytes, were rarely seen in tissue from either subgroup.
      CONCLUSIONS/INTERPRETATION: A modest increase in inflammatory activity was seen
      in subcutaneous adipose tissue from IR compared with equally obese IS
      individuals. Together with previous evidence of impaired adipose cell
      differentiation in IR vs equally obese individuals, it appears that at least two
      biological processes in subcutaneous adipose tissue characterize the insulin
      resistant state independent of obesity per se.

PMID- 18825364
TI  - [Frozen shoulder. Diagnosis and therapy].
AB  - The condition of shoulder stiffness is often called adhesive capsulitis or frozen
      shoulder. It is regarded as a distinct clinical entity showing a benign and
      regular course. The major clinical feature is significant reduction in both
      active and passive range of motion (ROM) accompanied by stage-dependent pain,
      allowing for a clinical diagnosis. There are primary and secondary forms, the
      former having an unknown etiology and increased occurrence in patients with
      metabolic disorders and the latter being seen with prior injury or operation.
      Three stages, each lasting 4-6 months, mark the clinical course. The progression
      of the disease is self-limiting and may occasionally resolve in partial
      restitution. In the first stage ("freezing"), the shoulder continuously loses
      passive motion and causes worsening pain. Continuing stiffness and improvements
      in pain and inflammation are characteristic of the second stage ("frozen"). In
      the third stage ("thawing"), restriction of shoulder motion decreases, and ROM
      increases. Treatment should be adjusted to these stages. Recommendations include
      analgesics and joint injections in the first stage and physiotherapy in
      combination with manual therapy in the second and third stages. In cases of
      failure, passive exercise under interscalene block, manipulation under general
      anesthesia, or arthroscopic arthrolysis should be considered.

PMID- 18825365
TI  - Ability of dynamic airway pressure curve profile and elastance for positive end
      expiratory pressure titration.
AB  - OBJECTIVE: To evaluate the ability of three indices derived from the airway
      pressure curve for titrating positive end-expiratory pressure (PEEP) to minimize
      mechanical stress while improving lung aeration assessed by computed tomography
      (CT). DESIGN: Prospective, experimental study. SETTING: University research
      facilities. SUBJECTS: Twelve pigs. INTERVENTIONS: Animals were anesthetized and
      mechanically ventilated with tidal volume of 7 ml kg(-1). In non-injured lungs (n
      = 6), PEEP was set at 16 cmH(2)O and stepwise decreased until zero. Acute lung
      injury was then induced either with oleic acid (n = 6) or surfactant depletion (n
      = 6). A recruitment maneuver was performed, the PEEP set at 26 cmH(2)O and
      decreased stepwise until zero. CT scans were obtained at end-expiratory and end
      inspiratory pauses. The elastance of the respiratory system (Ers), the stress
      index and the percentage of volume-dependent elastance (%E (2)) were estimated.
      MEASUREMENTS AND MAIN RESULTS: In non-injured and injured lungs, the PEEP at
      which Ers was lowest (8-4 and 16-12 cmH(2)O, respectively) corresponded to the
      best compromise between recruitment/hyperinflation. In non-injured lungs, stress
      index and %E (2) correlated with tidal recruitment and hyperinflation. In injured
      lungs, stress index and %E (2) suggested overdistension at all PEEP levels,
      whereas the CT scans evidenced tidal recruitment and hyperinflation
      simultaneously. CONCLUSION: During ventilation with low tidal volumes, Ers seems
      to be useful for guiding PEEP titration in non-injured and injured lungs, while
      stress index and %E (2) are useful in non-injured lungs only. Our results suggest
      that Ers can be superior to the stress index and %E (2) to guide PEEP titration
      in focal loss of lung aeration.

PMID- 18825366
TI  - Interactions between respiration and systemic hemodynamics. Part II: practical
      implications in critical care.
AB  - In Part I of this review, we have covered basic concepts regarding
      cardiorespiratory interactions. Here, we put this theoretical framework to
      practical use. We describe mechanisms underlying Kussmaul's sign and pulsus
      paradoxus. We review the literature on the use of respiratory variations of blood
      pressure to evaluate volume status. We show the possibilities of attaining the
      latter aim by investigating with ultrasonography how the geometry of great veins
      fluctuates with respiration. We provide a Guytonian analysis of the effects of
      PEEP on cardiac output. We terminate with some remarks on the potential of
      positive pressure breathing to induce acute cor pulmonale, and on the
      cardiovascular mechanisms that at times may underly the failure to wean a patient
      from the ventilator.

PMID- 18825367
TI  - Interactions between respiration and systemic hemodynamics. Part I: basic
      concepts.
AB  - The topic of cardiorespiratory interactions is of extreme importance to the
      practicing intensivist. It also has a reputation for being intellectually
      challenging, due in part to the enormous volume of relevant, at times
      contradictory literature. Another source of difficulty is the need to
      simultaneously consider the interrelated functioning of several organ systems
      (not necessarily limited to the heart and lung), in other words, to adopt a
      systemic (as opposed to analytic) point of view. We believe that the proper
      understanding of a few simple physiological concepts is of great help in
      organizing knowledge in this field. The first part of this review will be devoted
      to demonstrating this point. The second part, to be published in a coming issue
      of Intensive Care Medicine, will apply these concepts to clinical situations. We
      hope that this text will be of some use, especially to intensivists in training,
      to demystify a field that many find intimidating.

PMID- 18825368
TI  - The vasopressin and copeptin response in patients with vasodilatory shock after
      cardiac surgery: a prospective, controlled study.
AB  - OBJECTIVE: To evaluate arginine vasopressin (AVP) and copeptin plasma
      concentrations in patients with vasodilatory shock after cardiac surgery. DESIGN:
      Prospective, controlled, clinical study. SETTING: Surgical intensive care unit
      and cardiac surgery ward in a tertiary university teaching hospital. PATIENTS AND
      PARTICIPANTS: Thirty-three critically ill patients with vasodilatory shock after
      cardiac surgery and ten control patients undergoing uncomplicated aorto-coronary
      bypass surgery. MEASUREMENTS AND RESULTS: Hemodynamic, laboratory and clinical
      data were recorded daily in all patients during the first 7 days after cardiac
      surgery. At the same time, points blood was withdrawn to determine plasma
      concentrations of AVP (radioimmunoassay) and copeptin (immunoluminometric assy).
      Standard tests, a mixed effects model and regression analyses were used for
      statistical analysis. The course of AVP was significantly different between
      groups (P < 0.001). While AVP concentrations were lower in the study group on the
      first postoperative day, they were higher than that in the control group from
      postoperative day 3 on. There was no difference in the postoperative AVP response
      between study patients with or without chronic angiotensin-converting enzyme
      inhibitor therapy. Except during continuous veno-venous hemofiltration, AVP and
      copeptin correlated significantly with each other (P < 0.001; r = 0.749).
      CONCLUSIONS: The AVP response to cardiac surgery is significantly different
      between patients with vasodilatory shock and patients undergoing uncomplicated
      aorto-coronary bypass surgery. Although no causative relationship between AVP
      concentrations and cardiovascular instability can be drawn from these results,
      our data support the hypothesis that inadequately low AVP plasma levels
      contribute to the failure to restore vascular tone in vasodilatory shock after
      cardiac surgery.

PMID- 18825369
TI  - The epidemiology of acute respiratory distress syndrome in pediatric intensive
      care units in China.
AB  - OBJECTIVE: To assess the incidence of, predisposing factors for, and the rates
      and relative risks of mortality from acute respiratory distress syndrome (ARDS)
      in pediatric patients. DESIGN: A prospective study in 12 consecutive months from
      2004 to 2005 in 25 pediatric intensive care units (PICUs). PATIENTS AND SETTING:
      ARDS was diagnosed according to the 1994 American-European Consensus Conference
      definitions, applied to all severely ill admissions between 1 month and 14 years
      of age. The PICUs were in major municipalities and provincial cities, and half
      were university affiliated. MEASUREMENTS AND RESULTS: From a total of 12,018
      admissions, 7,269 were severely ill. One hundred and five (1.44%) patients
      developed ARDS and 64 (61.0%) died, which accounts for 13.2%, of the total ICU
      death (n = 485, 6.7%) or a nine times relative risk of dying. The median age at
      onset of ARDS was 24 months and 40% were less than 12 month old. Median time from
      PICU admission to the onset of ARDS was 16 h, and in 63% <24 h. Pneumonia (55.2%)
      and sepsis (22.9%) were the major predisposing factors for ARDS. These were
      respectively 14 and 5 times as high a death rate as those of the severely ill
      patients without ARDS. CONCLUSIONS: ARDS has a high mortality in these Chinese
      PICUs, especially in those with pneumonia and sepsis, and adequate management
      including lung protective ventilation strategy is required.

PMID- 18825370
TI  - (S)-reticuline induces vasorelaxation through the blockade of L-type Ca(2+)
      channels.
AB  - In Brazil, various species of the genus Ocotea are used in folk medicine for
      treating several diseases. The chemical characterization of this plant showed the
      presence of alkaloids belonging to the benzyltetrahydroisoquinoline family, the
      major component of which is (S)-reticuline. The present study investigated
      whether (S)-reticuline exerts an inhibitory effect on smooth muscle L-type Ca(2+)
      channels. Tension measurements and patch clamp techniques were utilized to study
      the effects of (S)-reticuline. Whole-cell Ca(2+) currents were measured using the
      A7r5 smooth muscle cell line. (S)-reticuline antagonized CaCl(2)- and KCl-induced
      contractions and elicited vasorelaxation. It also reduced the voltage-activated
      peak amplitude of I (Ca,L) in a concentration-dependent manner. (S)-reticuline
      did not change the characteristics of current density vs. voltage relationship.
      (S)-reticuline shifted leftwards the steady-state inactivation curve of I (Ca,L).
      The application of dibutyryl cyclic adenosine monophosphate to the cell decreased
      the amplitude of Ca(2+) currents. In cells pretreated with forskolin, an
      adenylate cyclase activator, the addition of (S)-reticuline caused further
      inhibition of the Ca(2+) currents suggesting an additive effect. The results
      obtained show that (S)-reticuline elicits vasorelaxation probably due to the
      blockade of the L-type voltage-dependent Ca(2+) current in rat aorta. The
      reported effect may contribute to the potential cardioprotective efficacy of (S)
      reticuline.

PMID- 18825371
TI  - Evidence for modulation of facial emotional processing bias during emotional
      expression decoding by serotonergic and noradrenergic antidepressants: an event
      related potential (ERP) study.
AB  - RATIONALE: Serotonergic (SSRI) and noradrenergic (NRI) antidepressants modulate
      biases in emotional processing such that perceptual bias is shifted away from
      negative and towards positive emotional material. However, the effects of
      serotonergic and noradrenergic modulation on the temporal course (occurring in
      milliseconds) of emotional processing, and in particular, the rapid physiological
      changes associated with the different stages of emotional processing, are
      unknown. OBJECTIVE: The current study assessed the effects of acute serotonergic
      (i.e. with citalopram) and noradrenergic (i.e. with reboxetine) augmentation on
      event-related potential (ERP) measures associated with 'structural encoding'
      (N170) and emotion expression decoding (N250 and late positive potential [LPP])
      for positive (happy) and negative (sad) facial stimuli relative to neutral facial
      stimuli. MATERIALS AND METHODS: This study employed a double-blind, placebo
      controlled, cross-over design in which 12 healthy male participants completed a
      facial expression recognition task tested under three acute conditions: (a)
      placebo, (b) citalopram (20 mg) and (c) reboxetine (4 mg). RESULTS: Both
      citalopram and reboxetine had no effect on the N170 ERP component associated with
      structural encoding, but potentiated the N250 associated with happy (relative to
      neutral) emotional facial expression decoding. Both drugs had no valence effects
      on later ERP measures of emotion expression decoding (LPP). CONCLUSIONS:
      Citalopram and reboxetine have selective effects on the temporal course of
      emotional processing with evidence to suggest specific effects on emotion
      expression decoding of positive (happy) emotional facial stimuli as evidenced by
      changes in the attention-modulated N250 but not structural encoding. These
      findings provide physiological evidence that antidepressants may shift perceptual
      biases in emotional processing away from negative and towards positive stimuli.

PMID- 18825372
TI  - The type 1 TNF receptor and its associated adapter protein, FAN, are required for
      TNFalpha-induced sickness behavior.
AB  - RATIONALE: During the course of an infection, the pro-inflammatory cytokine tumor
      necrosis factor alpha (TNFalpha) acts in the brain to trigger development of
      behavioral responses, collectively termed sickness behavior. Biological
      activities of TNFalpha can be mediated by TNF receptor type 1 (TNF-R1) and type 2
      (TNF-R2). TNFalpha activates neutral sphingomyelinase through the TNF-R1 adapter
      protein FAN (factor associated with neutral sphingomyelinase activation), but a
      behavioral role of FAN in the brain has never been reported. OBJECTIVES: We
      hypothesized that TNFalpha-induced sickness behavior requires TNF-R1 and that FAN
      is a necessary component for this response. MATERIALS AND METHODS: We determined
      the role of brain TNF-R1 in sickness behavior by administering an optimal amount
      of TNFalpha intracerebroventricularly (i.c.v., 50 ng/mouse) to wild-type (WT),
      TNF-R1-, TNF-R2-, and FAN-deficient mice. Sickness was assessed by decreased
      social exploration of a novel juvenile, induction of immobility, and loss of body
      weight. RESULTS: TNF-R1-deficient mice were resistant to the sickness-inducing
      properties of i.c.v. TNFalpha, whereas both TNF-R2-deficient and WT mice were
      fully responsive. Furthermore, the complete absence of TNFalpha-induced sickness
      behavior in FAN-deficient mice provided in vivo evidence that FAN-dependent TNF
      R1 signaling is critical for this central action of TNFalpha. CONCLUSIONS: This
      is the first report to demonstrate that TNFalpha-induced sickness behavior is
      fully mediated by TNF-R1 and that the adaptor protein FAN is a necessary
      intracellular intermediate for sickness behavior.

PMID- 18825373
TI  - The effects of psychotomimetic and putative cognitive-enhancing drugs on the
      performance of a n-back working memory task in rats.
AB  - RATIONALE: Working memory impairment is a core symptom of schizophrenia, but no
      existing treatment remediates this deficit. Inconsistent conceptualizations and
      few reliable translational measures are major hindrances to understanding the
      neurobiology of this aspect of cognition. Using comparable task designs may help
      bridge clinical and preclinical research efforts. OBJECTIVE: A novel rodent
      procedure was designed to translate the n-back working memory task used in
      schizophrenic patients. MATERIALS AND METHODS: Rats were trained in five-lever
      operant chambers to recall either the last (one-back) or penultimate (two-back)
      lever from random sequences of lever presentations of variable lengths.
      Psychotomimetic doses of amphetamine, dizocilpine maleate (MK801), and (+/-)-2,5
      dimethoxy-4-iodoamphetamine hydrochloride (DOI) were tested for disruption of
      accuracy, and cognitive-enhancing doses of amphetamine, nicotine, and (+/-)-1
      phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol hydrochloride (SKF38393
      hydrochloride) were examined for improvements in performance. RESULTS: High doses
      of amphetamine (0.8 and 1.6 mg/kg) significantly reduced accuracy while
      increasing total trials; 0.1 mg/kg MK801 and 2.0 mg/kg DOI also reduced accuracy,
      but the latter concurrently impaired responding. At the lowest dose (0.2 mg/kg),
      amphetamine increased total trials and rewards without affecting accuracy; 1.0
      mg/kg nicotine reduced accuracy without affecting total trials, whereas 10.0
      mg/kg SKF38393 had the opposite effect. DISCUSSION: Although the possibility for
      mediating behaviors may exist, the rodent n-back task provides a clinically
      relevant model of working memory. Amphetamine and MK801 produced selective
      impairments without disrupting responding. The cognitive enhancers did not
      improve working memory, but low doses of amphetamine improved response
      efficiency. This novel procedure may be useful for examining cognitive deficits
      and their potential reversal in animal models of schizophrenia.

PMID- 18825374
TI  - How to use time more efficiently.

PMID- 18825375
TI  - Roles and responsibilities of graduate students and post-docs.

PMID- 18825376
TI  - Sulfur trace determination in petroleum products by isotope dilution ICP-MS using
      direct injection by thermal vaporization (TV-ICP-IDMS).
AB  - An accurate, sensitive, and fast method for direct determination of total sulfur
      in petroleum products after thermal vaporization of an isotope-diluted sample was
      developed by using ICP-MS. (34)S-labelled dibenzothiophene spike was used for the
      isotope dilution step. The isotope-diluted sample was injected into a thermal
      vaporizer which was directly connected by a heated transfer line to the plasma
      torch. Sample transport was achieved by using a helium gas flow, and the isotope
      ratio (34)S/(32)S was determined within seconds after injection. No other sample
      preparation other than the simple and fast isotope dilution step, which enables
      accurate and sensitive determination of sulfur at high sample throughputs, is
      necessary. Thus, this technique fits all needs for routine analyses. Validation
      of the TV-ICP-IDMS method was carried out by analyzing the certified gas oil
      reference materials BCR672 and BCR107. Comparison of results for noncertified low
      and high-boiling samples, obtained from an ICP-IDMS microwave-assisted digestion
      method, also resulted in very good agreement. The low detection limit of 40 ng/g
      and the large dynamic range of TV-ICP-IDMS fulfill all necessities to allow
      analysis of sulfur in different petroleum products, e.g., even at the low
      concentration level of 'sulfur-free' gasoline.

PMID- 18825377
TI  - Attitudes among hospital physicians to the reporting of adverse drug reactions in
      Sweden.
AB  - OBJECTIVES: This study was designed to investigate attitudes to and incentive for
      reporting adverse drug reactions (ADRs) in general and towards nurses as
      reporters of ADRs in particular in a sample of hospital physicians. METHOD: A
      questionnaire was sent to 1,201 randomly selected hospital physicians. RESULTS:
      The main factors for the decision to report an ADR were the severity of the
      reaction, a reaction to a new drug, and an unusual reaction. The most important
      factor for refraining from reporting was that the reaction was well known. There
      were no significant differences between males and females or between age groups
      in these aspects. A majority were positive or neutral to nurses as reporters.
      Only 6% stated that their willingness to report ADRs would be affected in a
      negative way if nurses were involved in the program for reporting. CONCLUSIONS:
      The results of this survey showed that inclusion of hospital nurses as reporters
      will not decrease the reporting rate from the physicians.

PMID- 18825378
TI  - Serial (1)H-MRS of thalamus during deep brain stimulation of bilateral globus
      pallidus internus for primary generalized dystonia.
AB  - INTRODUCTION: The physiological mechanisms of deep brain stimulation (DBS) are
      not completely clear. Our understanding of them may be facilitated with the use
      of proton magnetic resonance spectroscopy ((1)H-MRS). METHODS: Serial (1)H-MRS of
      both thalami was performed during the course of DBS of bilateral globus pallidus
      internus in a patient with primary generalized dystonia. RESULTS: Two days after
      microelectrode implantation, a pulse frequency of 185 Hz was applied for
      stimulation. It resulted in relief of symptoms and a decrease of Burke-Fahn
      Marsden dystonia rating scale (BFMDRS) scores, and was accompanied by a prominent
      increase of N-acetylaspartate (NAA)/choline-containing compounds (Cho) ratio, a
      mild increase of NAA/creatine (Cr) ratio, and a moderate decrease of Cho/Cr
      ratio. Two weeks later, for a search of the optimal stimulation mode, the pulse
      frequency was switched to 60 Hz, which resulted in clinical deterioration and
      significant increase of BFMDRS scores. At that time, all investigated (1)H-MRS
      detected metabolic parameters had nearly returned to the pretreatment levels.
      CONCLUSION: Use of serial (1)H-MRS investigations of various brain structures
      during DBS in cases of movement disorders permits detailed evaluation of the
      treatment response, has a potential for its possible prediction, and may
      facilitate understanding of the physiological mechanisms of stimulation.

PMID- 18825379
TI  - A novel goose-type lysozyme gene with chitinolytic activity from the moderately
      thermophilic bacterium Ralstonia sp. A-471: cloning, sequencing, and expression.
AB  - In this study, we cloned the gene encoding goose-type (G-type) lysozyme with
      chitinase (Ra-ChiC) activity from Ralstonia sp. A-471 genomic DNA library. This
      is the first report of another type of chitinase after the previously reported
      chitinases ChiA (Ra-ChiA) and ChiB (Ra-ChiB) in the chitinase system of the
      moderately thermophilic bacterium, Ralstonia sp. A-471 and also the first such
      data in Ralstonia sp. G-type lysozyme gene. It consisted of 753 bp nucleotides,
      which encodes 251 amino acids including a putative signal peptide. This ORF was
      modular enzyme composed of a signal sequence, chitin-binding domain, linker, and
      catalytic domain. The catalytic domain of Ra-ChiC showed homologies to those of G
      type lysozyme (glycoside hydrolases (GH) family 23, 16.8%) and lysozyme-like
      enzyme from Clostridium beijerincki (76.1%). Ra-ChiC had activities against
      ethylene glycol chitin, carboxyl methyl chitin, and soluble chitin but not
      against the cell wall of Micrococcus lysodeikticus. The enzyme produced alpha
      anomer by hydrolyzing beta-1,4-glycosidic linkage of the substrate, indicating
      that the enzyme catalyzes the hydrolysis through an inverting mechanism. When N
      acetylglucosamine hexasaccharide [(GlcNAc)6] was hydrolyzed by the enzyme, the
      second and third glycosidic linkage from the non-reducing end were split
      producing (GlcNAc)2 + (GlcNAc)4 and (GlcNAc)3 + (GlcNAc)3 of almost the same
      concentration in the early stage of the reaction. The G-type lysozyme hydrolyzed
      (GlcNAc)6 in an endo-splitting manner, which produced (GlcNAc)3 + (GlcNAc)3
      predominating over that to (GlcNAc)2 + (GlcNAc)4. Thus, Ra-ChiC was found to be a
      novel enzyme in its structural and functional properties.

PMID- 18825380
TI  - Bernard-Soulier syndrome: novel nonsense mutation in GPIbbeta gene affecting GPIb
      IX complex expression.
AB  - Bernard-Soulier syndrome (BSS) is a rare autosomal recessive genetic disorder
      characterized by thrombocytopenia, circulating giant platelets, and prolonged
      bleeding time. BSS is explained by a defect in primary hemostasis owing to
      quantitative or qualitative defect in the GPIb-IX-V complex, composed of four
      subunits: GPIbalpha, GPIbbeta, GPIX, and GPV. In this study, we report a novel
      GPIbbeta defect in a Tunisian family, in which Serine 23 is substituted by a Stop
      codon causing a premature termination of translation. This defect was homozygous
      in the BSS patient and heterozygote in both the parents and sisters of the
      patient. We studied the effect of this mutation on the expression of the GPIb-IX
      complex by western blot, flow cytometry, and confocal microscopy: GPIbalpha and
      GPIX were absent on the surface of platelets, whereas they were present in the
      cytoplasm. These results led to conclude that the novel Ser 23 Stop mutation in
      GPIbbeta is responsible of BSS in the studied family and hampers the complex to
      form on the platelets surface.

PMID- 18825381
TI  - Multi-center phase II trial of chemo-radiotherapy with 5-fluorouracil, leucovorin
      and oxaliplatin in locally advanced esophageal cancer.
AB  - PURPOSE: The aim of this study was to evaluate the activity and safety of
      oxaliplatin/5-fluorouracil-based chemo-radiotherapy in patients with not
      radically resectable locally advanced esophageal cancer. METHODS: Fifty-nine
      patients with adeno or squamous-cell carcinoma received oxaliplatin (60 mg/m(2)),
      and leucovorin (20 mg/m(2) on days 1,8,15,29,36,43,50,57) followed by continuous
      infusion fluorouracil (200 mg/m(2) per day on days 1-22 and 29-64) with
      radiotherapy (1.8 Gy daily fractions to a total dose of 45 Gy, from days 29 to
      64). When feasible, surgery was scheduled 6-8 weeks after chemo-radiotherapy
      completion. The primary endpoint was 1-year progression-free survival. RESULTS:
      Forty (68%) patients completed treatment without modifications. An objective
      clinical response was seen in 35 patients (59%). Esophagectomy was possible in 33
      patients and a complete resection (R0) was achieved in 26 (79%) with 6 pathologic
      complete responses (pCR) and 3 near pCR. At a median follow-up of 39.7 months for
      the surviving patients, the median progression-free and overall survivals were 11
      months (95% CI 6.5-14) and 18.5 months (95% CI 13-29). The 1-year progression
      free and overall survivals were 47.5% (95% CI 34-59.5%) and 63% (95% CI 49-74%).
      Major toxicities were esophagitis (20% G3 and 5% G4) and diarrhea (8.5% G3 and
      8.5% G4). Hematological toxicity (7% G3 and 3% G4) was less common; severe
      neurotoxicity (3% G3) was infrequent. CONCLUSIONS: Concurrent oxaliplatin,
      leucovorin, fluorouracil and radiotherapy followed or not by esophagectomy has a
      tolerable toxicity and promising activity in locally advanced esophageal cancer.

PMID- 18825382
TI  - Linear quadratic and tumour control probability modelling in external beam
      radiotherapy.
AB  - The standard linear-quadratic (LQ) survival model for external beam radiotherapy
      is reviewed with particular emphasis on studying how different schedules of
      radiation treatment planning may be affected by different tumour repopulation
      kinetics. The LQ model is further examined in the context of tumour control
      probability (TCP) models. The application of the Zaider and Minerbo non
      Poissonian TCP model incorporating the effect of cellular repopulation is
      reviewed. In particular the recent development of a cell cycle model within the
      original Zaider and Minerbo TCP formalism is highlighted. Application of this TCP
      cell-cycle model in clinical treatment plans is explored and analysed.

PMID- 18825383
TI  - Genetic transformation and regeneration of Sesbania drummondii using cotyledonary
      nodes.
AB  - Sesbania drummondii (Rydb.) Cory is a source for phytopharmaceuticals. It also
      hyperaccumulates several toxic heavy metals. Development of an efficient gene
      transfer method is an absolute requirement for the genetic improvement of this
      plant with more desirable traits due to limitations in conventional breeding
      methods. A simple protocol was developed for Agrobacterium-mediated stable
      genetic transformation of Sesbania. Agrobacterium tumefaciens strain EHA 101
      containing the vector pCAMBIA 1305.1 having hptII and GUS plus genes was used for
      the gene transfer experiments. Evaluation of various parameters was carried out
      to assess the transformation frequency by GUS expression analysis. High
      transformation frequency was achieved by using 7-day-old precultured cotyledonary
      node (CN) explants. Further, the presence of acetosyringone (150 muM), infection
      of explants for 30-45 min and 3 days of cocultivation proved to be critical
      factors for greatly improving the transformation efficiency. Stable
      transformation of S. drummondii was achieved, and putative transgenic shoots were
      obtained on medium supplemented with hygromycin (25 mg l(-1)). GUS histochemical
      analysis of the putative transgenic tissues further confirmed the transformation
      event. Genomic Southern blot analysis was performed to verify the presence of
      transgenes and their stable integration. A transformation frequency of 4% was
      achieved for CN explants using this protocol.

PMID- 18825384
TI  - GMCHI, cloned from soybean [Glycine max (L.) Meer.], enhances survival in
      transgenic Arabidopsis under abiotic stress.
AB  - Plants respond to cold stress by modifying the expression of a battery of cold
      responsive genes. Using cDNA-AFLP techniques, GMCHI (G lycine m ax chilling
      inducible) (accession no. EU699765) was isolated from the embryonic axis of a
      chilling-resistant cultivar of soybean seed imbibed at 4 degrees C for 24 h. The
      full-length GMCHI cDNA which consisted of a single open reading frame (ORF)
      encoded a putative polypeptide of 129 amino acids. Sequence analysis revealed
      neither significant similarity of GMCHI to known proteins, nor any conserved
      domains found. Soybean seed imbibed at 4 degrees C dramatically enhanced
      transcript level of GMCHI after 1 h, and reached a maximum at 18 h, while the
      expression was only detected in the embryonic axis. GMCHI expression was strongly
      induced by treatment with ABA and PEG, but weakly by 250 mM NaCl which suggests
      that GMCHI is probably regulated by ABA-dependent signal transduction pathway
      during cold acclimation. Overexpression of GMCHI in Arabidopsis under the control
      of CaMV35S promoter enhanced the tolerance to cold, drought and NaCl stresses.
      Therefore, GMCHI may play an important role in the adaptation of chilling
      resistant soybean seed to chilling imbibition.

PMID- 18825385
TI  - CT of pulmonary emphysema--current status, challenges, and future directions.
AB  - Pulmonary emphysema is characterized by irreversible destruction of lung
      parenchyma. Emphysema is a major contributor to chronic obstructive pulmonary
      disease (COPD), which by itself is a major cause of morbidity and mortality in
      the western world. Computed tomography (CT) is an established method for the in
      vivo analysis of emphysema. This review first details the pathological basis of
      emphysema and shows how the subtypes of emphysema can be characterized by CT. The
      review then shows how CT is used to quantify emphysema, and describes the
      requirements and foundations for quantification to be accurate. Finally, the
      review discusses new challenges and their potential solution, notably focused on
      multi-detector-row CT, and emphasizes the open questions that future research on
      CT of pulmonary emphysema will have to address.

PMID- 18825386
TI  - Endorectal magnetic resonance imaging at 1.5 Tesla to assess local recurrence
      following radical prostatectomy using T2-weighted and contrast-enhanced imaging.
AB  - To evaluate diagnostic performance of endorectal magnetic resonance (eMR) for
      diagnosing local recurrence of prostate cancer (PC) in patients with previous
      radical prostatectomy (RP) and to assess whether contrast-enhanced (CE)-eMR
      improved diagnostic accuracy in comparison to unenhanced study. Unenhanced eMR
      data of 72 male patients (mean of total PSA: 1.23 +/- 1.3 ng/ml) with previous RP
      were interpreted retrospectively and classified either as normal or suspicious
      for local recurrence. All eMR examinations were re-evaluated also on CE-eMR 4
      months after the first reading. Images were acquired on a 1.5-T system. These
      data were compared to the standard of reference for local recurrence:
      prostatectomy bed biopsy results; choline positron emission tomography results;
      PSA reduction or increase after pelvic radiotherapy; PSA modification during
      active surveillance. Sensitivity, specificity, predictive positive value,
      negative predictive value and accuracy were 61.4%, 82.1%, 84.4%, 57.5% and 69.4%
      for unenhanced eMR and 84.1%, 89.3%, 92.5%, 78.1% and 86.1% for CE-eMR. A
      statistically significant difference was found between accuracy and sensitivity
      of the two evaluations (chi(2) = 5.33; p = 0.02 and chi(2) = 9.00; p = 0.0027).
      EMR had great accuracy for visualizing local recurrence of PC after RP. CE-eMR
      improved diagnostic performance in comparison with T2-weighted imaging alone.

PMID- 18825387
TI  - Cloning of sarco-endoplasmic reticulum Ca2+ -ATPase (SERCA) from Caribbean spiny
      lobster Panulirus argus.
AB  - We have previously reported on calcium transport mechanisms in American lobster,
      Homarus americanus, using (45)Ca(2+) coupled with vesicle preparations of
      hepatopancreatic endoplasmic reticulum. The active transport of calcium across
      membranes bordering calcium-sequestering stores such as sarcoplasmic or
      endoplasmic reticulum is catalyzed by membrane-spanning proteins, the sarco
      endoplasmic Ca(2+)-ATPases (SERCAs). In the study described here we used advanced
      bioinformatics and molecular techniques to clone SERCA from the economically
      important Caribbean spiny lobster, Panulirus argus. We report the complete
      cloning of a full-length SERCA from P. argus antenna cDNA (GenBank accession
      number AY702617). This cDNA has a 1020-amino acid residue open reading frame
      which is 90% identical to published sequences of other crustacean SERCA proteins.
      Our data support the hypothesis that one crustacean and three vertebrate genes
      controlling calcium transport were derived from a common ancestral gene.

PMID- 18825388
TI  - High expression of Foxp3, IL-23p19 and survivin mRNA in colorectal carcinoma.
AB  - INTRODUCTION: Cytokines have been suggested to both modulate anti-tumor responses
      and promote tumor growth. MATERIALS AND METHODS: We analyzed the expression of
      pro-inflammatory IL-12p35, IL-12p40, IL-23p19, anti-inflammatory IL-10,
      antiapoptotic factor survivin, and transcription factors-RelA, c-Jun, and Foxp3
      mRNA in patients' blood, colon carcinoma tissue, and in normal mucosal tissue by
      real-time polymerase chain reaction. The quantity determination of serum IL
      12p40, IL-23, and IL-10 was performed by enzyme-linked immunosorbent assay.
      RESULTS: We observed significantly higher levels in patients for all three
      analyzed cytokines, with IL-23 concentration change being the highest. We
      detected the greatest upregulation of IL-23p19, Foxp3 and survivin mRNA in
      colorectal carcinomas than normal mucosa. A statistically significant
      upregulation of IL-12p40, IL-10, and c-Jun mRNA but not for IL-12p35 and RelA
      mRNA in tumor tissue comparing to normal tissue was also established.
      CONCLUSIONS: In conclusion, we show a characteristic gene expression profile
      combining markers associated with inhibition of anti-tumor immune response
      (Foxp3, IL-10), inhibition of apoptosis (survivin), and induction of the
      cytokines with protumoral activity as IL-12p40 and IL-23p19 (IL-23) in the
      colorectal tumor tissue but not in peripheral blood of patients.

PMID- 18825389
TI  - An orthotopic nude mouse model for preclinical research of gastric cardia cancer.
AB  - PURPOSE: A clinically relevant animal model for cancer of the esophagogastric
      junction does not exist. This study aimed to establish an orthotopic mouse model
      for human gastric cancer of the distal stomach and the gastric cardia. MATERIALS
      AND METHODS: Human gastric cancer cell lines AGS, MKN-45, and NCI-N87 were
      injected subcutaneously into nude mice. These donor tumors were harvested after 4
      weeks and minced into small tumor fragments. One donor tumor fragment was
      orthotopically implanted into the submucosa of either gastric cardia or distal
      stomach in other mice. The animals were killed 4, 8, and 12 weeks after tumor
      implantation. Volume of the primary tumor and local and systemic tumor spread
      were determined. RESULTS: The implantation technique resulted in a tumor take
      rate of 100%. An artificial dissemination of tumor cells into the abdominal
      cavity due to the procedure was not observed. CONCLUSIONS: We report for the
      first time the development of a clinically relevant mouse model for human gastric
      cancer of the gastric cardia and the distal stomach. Primary tumor growth and
      local and systemic spread progressed continuously during the observation period
      and mimic the human situation of this disease. This model may be suitable to
      evaluate novel treatment strategies for this malignancy.

PMID- 18825391
TI  - [Quality assurance and guidelines in rehabilitation for musculoskeletal
      diseases].
AB  - Diseases of the musculoskeletal system are among the most common and most costly
      diseases in Germany. They are also associated with a considerable burden for
      those affected. As a result these disorders also dominate the utilization
      statistics with respect to medical rehabilitation measures paid for by the
      statutory pension insurance. In the last 10 years, quality assurance programs
      have been developed for rehabilitation--initiated and financed by the
      rehabilitation sponsors--that are characterized by a comprehensive, perspective,
      pronounced scientific basis, region-wide implementation, and strong patient
      orientation. The development of guidelines for rehabilitation began later than
      for acute medicine. In addition to the formulation of guidelines for
      rehabilitation by medical organizations and professional associations, the German
      pension insurance has developed so-called process guidelines containing framework
      requirements for the treatment of defined indication groups rather than support
      for decision-making in the rehabilitation of individual patients. By planned
      control of adherence to the process guidelines in the quality assurance programs
      of the pension insurers prompt implementation of the guidelines can be
      anticipated.

PMID- 18825392
TI  - [Using the International Classification of Functioning, Disability, and Health in
      rheumatologic rehabilitation].
AB  - The International Classification of Functioning, Disability, and Health (ICF)
      created by the World Health Organization provides both a framework and a
      classification comprehensively covering domains of function and disability in
      rheumatologic patients. The ICF can be used as a universal language understood by
      medical doctors, health professionals, researchers, patients, and other groups.
      It is based on an integrative biopsychosocial model of functioning. For its
      implementation in rheumatology and medicine in general, practical ICF-based tools
      such as the ICF Core Sets are necessary. These Sets, which were developed in a
      standardized scientific process, consist of the ICF categories that are most
      relevant for a specific group of patients, e.g. chronic patients with rheumatoid
      arthritis. In rheumatologic rehabilitation, patient problems, medical findings,
      treatment goals, and treatment concepts can be structured by applying the ICF,
      ICF Core Sets, and an ICF assessment sheet to patients. In outcomes research, ICF
      Core Sets can support the selection of relevant outcome domains.

PMID- 18825393
TI  - [Rehabilitation and outpatient physiotherapy in rheumatic disease patients.
      Results of cross-sectional studies of patients with rheumatoid arthritis or
      ankylosing spondylitis and rheumatologists].
AB  - Rehabilitation and outpatient physiotherapy were investigated from the
      perspectives of patients suffering from rheumatoid arthritis (RA) or ankylosing
      spondylitis (AS) and of rheumatologists. In 2007, 204 outpatients with RA and 47
      with AS at the Arthritis Center in Halle, Germany, and 117 rheumatologists from
      all over the country participated in two questionnaire surveys. Patients and
      rheumatologists gave predominantly positive judgements of physiotherapy,
      psychological interventions, and patient education programs. However, outpatient
      care including these interventions was judged to be mainly limited by fixed
      budgets and other formal restrictions. Even though these therapeutic options are
      part of (primarily inpatient) rehabilitation programs, the estimate of the need
      for multidisciplinary rehabilitation programs varied widely among the
      rheumatologists. Significant objections against rehabilitation include reluctance
      of the patients, administrative burden for the physicians, payers' rejections,
      and limited choice of rehabilitation clinic. Despite major functional
      limitations, a substantial portion of the patients received no multidisciplinary
      medical rehabilitation, outpatient physiotherapy, psychological interventions, or
      patient education. Recommendations for the improvement of care are derived from
      these data.

PMID- 18825394
TI  - Differences in patellofemoral contact stresses between mobile-bearing and fixed
      bearing total knee arthroplasties: a dynamic in vitro measurement.
AB  - INTRODUCTION: Anterior knee pain is one of the most common problems after total
      knee arthroplasty (TKA). Mobile-bearing designs should improve patella tracking
      with a reduced rate of patella tilt as well as reduced patellofemoral contact
      stresses and improve knee flexion. The aim of this dynamic in vitro investigation
      was to evaluate the changes of patellofemoral contact stresses after TKA using
      fixed and mobile-bearing designs. MATERIALS AND METHODS: Seven knee specimens
      were mounted into a knee simulator imitating an isokinetic extension of the knee.
      The patellofemoral contact was measured before and after tricompartimental TKA
      with fixed and mobile-bearing designs using pressure-sensitive films. Contact
      stresses were measured from 120 degrees knee flexion to full extension with a
      simulated force of the quadriceps muscle up to 1,200 N. Additionally all
      measurements were performed with simulated co-contraction of the hamstrings
      muscles. RESULTS: Fixed-bearing TKA increases patellofemoral contact stresses
      compared to physiologic conditions. After patella resurfacing, contact stresses
      increase even more. By changing the prosthesis design to mobile bearing, maximum
      contact stress was measured to be punctual higher than in fixed-bearing implants.
      In the interval between 0 degrees -30 degrees and 70 degrees -105 degrees of
      flexion, obviously lower pressures were evaluated for the mobile-bearing design.
      With cocontraction of the hamstrings, a lower contact stress of the mobile
      bearing design was evident for the complete measurement of the knee extension.
      CONCLUSION: An increase of patellofemoral contact stresses after patellar
      resurfacing in TKA could be demonstrated. This outcome implicates a higher risk
      of patellofemoral complications. The mobile-bearing design showed evidently lower
      patellofemoral contact stresses than the fixed-bearing design.

PMID- 18825395
TI  - The usefulness of dual energy X-ray and laser absorptiometry of the calcaneus
      versus dual energy X-ray absorptiometry of hip and spine in diagnosing manifest
      osteoporosis.
AB  - INTRODUCTION: Osteoporosis is a major health problem. Dual energy X-ray
      absorptiometry (DXA) of the hip and spine is the worldwide standard in diagnosing
      osteoporosis. Measurement of bone mineral density (BMD) with dual energy X-ray
      and laser absorptiometry of the calcaneus (Calscan) might be a good alternative.
      Advantages of the Calscan are that it is quick, widely available and manageable.
      In this study we compared BMD expressed in T-scores measured by DXA and Calscan.
      The aim of this study was to define threshold T-scores on the Calscan that could
      exclude or predict osteoporosis correctly in comparison with DXA. MATERIALS AND
      METHODS: Patients > or =50 years attending our emergency department with a
      fracture were offered osteoporosis screening at our fracture and osteoporosis
      outpatient clinic (FO-Clinic) and enrolled in this study. BMD was measured at the
      hip and spine using DXA and at the calcaneus using Calscan. A T-score measured by
      DXA < or =-2 standard deviations (SD) below the reference population was defined
      as manifest osteoporosis and was the treatment threshold. RESULTS: During a 10
      month study period, 182 patients were screened with both devices. The mean DXA-T
      score was -1.63 SD (range -4.9 to 2.1) and Calscan T-score -1.91 SD (range -5.3
      to 1.4). There was a significant correlation between both devices (r = 0.47, P <
      0.01). Using an upper threshold for the Calscan T-score of -1.3 SD, 47 patients
      could be classified as non-osteoporotic with 89.3% sensitivity (95% CI 80.0
      95.3%). Using a lower threshold for the Calscan T-score of -2.9 SD, 34 patients
      could be classified by the Calscan as osteoporotic with 90.7% specificity (95% CI
      83.5-95.4). The remaining 101 patients could only be correctly classified by DXA
      T-scores. CONCLUSION: Although DXA is the established modality worldwide in
      measuring BMD it is restricted to specialized centres. Peripheral bone
      densitometers like the Calscan are widely available. When BMD measurements with
      DXA were compared to Calscan measurements it was possible to correctly classify
      81 of 182 patients based on the Calscan T-score. Of these 81 patients 34 could be
      classified as manifest osteoporotic and 47 as non-osteoporotic. Therefore the
      Calscan seems to be a promising technique which might be used as a screening
      device at a FO-Clinic, especially when DXA is not easily available.

PMID- 18825396
TI  - The recovery of 5-HT transporter and 5-HT immunoreactivity in injured rat spinal
      cord.
AB  - STUDY DESIGN: Experimental spinal cord injury. OBJECTIVE: To determine the role
      of serotonin (5-HT) and 5-HT transporter in recovery from spinal cord injury.
      METHOD: We examined 5-HT and 5-HT transporter of spinal cord immunohistologically
      and assessed locomotor recovery after extradural compression at the thoracic (T8)
      spinal cord in 21 rats. Eighteen rats had laminectomy and spinal cord injury,
      while the remaining three rats received laminectomy only. All rats were evaluated
      every other day for 4 weeks, using a 0-14 point scale open field test. RESULTS:
      Extradural compression markedly reduced mean hindlimbs scores from 14 to 1.5 +/-
      2.0 (mean +/- standard error of mean). The rats recovered apparently normal
      walking by 4 weeks. The animals were perfused with fixative 1-3 days, 1, 2 and 4
      weeks (three rats in each) after a spinal cord injury. The 5-HT transporter
      immunohistological study revealed a marked reduction of 5-HT transporter
      containing terminals by 1 day after injury. By 4 weeks after injury, 5-HT
      transporter immunoreactive terminals returned to the control level. The 5-HT
      immunohistological study revealed a reduction of 5-HT-containing terminals by 1
      week after injury. By 4 weeks after injury, 5-HT immunoreactive fibers and
      terminals returned to the control level. CONCLUSION: We estimated the recovery of
      5-HT transporter and 5-HT neural elements in lumbosacral ventral horn by ranking
      5-HT transporter and 5-HT staining intensity and counting 5-HT and 5-HT
      transporter terminals. The return of 5-HT transporter and 5-HT immunoreactivity
      of the lumbosacral ventral horn correlated with locomotor recovery, while 5-HT
      transporter showed closer relationship with locomotor recovery than 5-HT. The
      presence of 5-HT transporter indicates that the 5-HT fibers certainly function.
      This study shows that return of the function of 5-HT fibers predict the time
      course and extent of locomotory recovery after thoracic spinal cord injury.

PMID- 18825397
TI  - Deep vein thrombosis after total hip arthroplasty in Korean patients and D-dimer
      as a screening tool.
AB  - INTRODUCTION: This prospective study was designed to confirm risk factors and to
      assess the incidence of deep vein thrombosis after total hip and surface
      replacement arthroplasty in Korean patients not receiving anticoagulation
      prophylaxis and to determine efficacy of plasma D-dimer levels as a screening
      test. MATERIALS AND METHODS: From May 2003 to August 2004, 221 consecutive
      patients undergoing unilateral total hip arthroplasty and hip resurfacing were
      evaluated. All patients underwent ultrasonography preoperatively and venography
      and/or ultrasonography on postoperative day 7. Plasma D-dimer levels were
      estimated by latex immuno-assay preoperatively and on days 3 and 7
      postoperatively. RESULTS: Of the 221 patients in our cohort, 23 developed deep
      vein thrombosis (10.4%). Age (r = 0.245, P < 0.001) and gender (r = 0.155, P =
      0.021) significantly correlated with deep vein thrombosis. Rise in incidence
      paralleled increase in age (X(2) = 32.860, P < 0.001). D-dimer levels on
      postoperative days 3 (gamma = 0.364, P < 0.001) and 7 (gamma = 0.470, P < 0.001)
      were significantly correlated to the development of DVT. CONCLUSION: While
      incidence of deep vein thrombosis in Korean population after THA was lower than
      that in the West; it increased with age, and in female gender. Significant
      correlation was found between D-dimer levels and the development of deep vein
      thrombosis.

PMID- 18825399
TI  - TNF-alpha production in the skin.
AB  - Upregulation of TNF-alpha is a key early response to ultraviolet B (UVB) by
      keratinocytes (KCs), and represents an important component of the inflammatory
      cascade in skin. UVB irradiation induces TNF-alpha expression in both KCs and
      dermal fibroblasts, with TNF-alpha mRNA induction seen as early as 1.5 h after
      UVB. We previously reported that the effects are wavelength-specific: TNF-alpha
      expression and secretion are induced by UVB (290-320 nm), but not by UVA (320-400
      nm). Moreover, we found that IL-1alpha, a cytokine also present in irradiated
      skin, substantially and synergistically enhances the induction of TNF-alpha by
      UVB, and the induction of TNF-alpha by this combination of UVB with IL-1alpha is
      mediated through increased TNF-alpha gene transcription. We investigated the
      molecular mechanism for UVB-induction of the TNF-alpha gene with a series of TNF
      alpha promoter constructs, ranging from 1.2 kbp (from -1179 to +1 with respect to
      the TNF-alpha transcription initiation site) down to 0.1 kbp (-109 to +1), each
      driving expression of a CAT reporter. Our results showed a persistent nine to
      tenfold increase of CAT activity in all TNF-alpha promoter/reporter constructs in
      response to UVB (30 mJ/cm(2)) exposure. These results indicate the presence of
      UVB-responsive cis-element(s) located between -109 and +1 of the TNF-alpha
      promoter, a region that contains a putative AP-1 site and a putative NFkB site.
      UVB-induction was abolished when the TNF-alpha promoter was mutated by one base
      pair at the AP-1 binding site. Cells treated with SP600125, an AP-1 inhibitor
      that inhibits JNK (c-Jun N-terminal kinase), also showed suppression of the 0.1
      kbp TNF-alpha promoter/reporter construct. The authentic endogenous gene in
      untransfected cells was also blocked by the inhibitor. Electrophoretic Mobility
      Shift Assay indicated new complexes from UVB-treated nuclear extracts and anti
      phospho-c-Jun, a regulatory component of the AP-1 transcription factor, creating
      a supershift indicating increased phosphorylation of c-Jun and hence higher AP-1
      activity. Keratinocyte-derived TNF-alpha is a component of the early induction
      phase of the inflammatory cascade.

PMID- 18825400
TI  - Functional outcomes and rehabilitation strategies in patients treated with
      chemoradiotherapy for advanced head and neck cancer: a systematic review.
AB  - Organ preservation with radiotherapy and concomitant chemotherapy has become an
      accepted treatment modality in advanced head and neck cancer. Unfortunately,
      organ preservation is not synonymous with function preservation. The aim of this
      review was to systematically assess the effects of the disease and
      chemoradiotherapy (CRT) on functions such as swallowing, mouth opening,
      nutrition, pain and quality of life in patients with head and neck cancer.
      Another aim was to search for (evidence-based) techniques or strategies known to
      alleviate or rehabilitate the loss of function(s) associated with CRT. Two
      databases were searched (time period, January 1997 to August 2007) for the terms
      head and neck cancer, chemotherapy or cisplatin and radiotherapy, and the
      functional outcomes swallowing, trismus, nutrition, pain and quality of life or a
      variation of those words. In total, 15 relevant articles were identified that met
      the inclusion criteria. The majority of the studies that met the criteria focused
      on the outcomes swallowing, quality of life, and nutrition. Two studies reported
      on the outcome pain, but no paper reported on the outcome trismus. Only two
      papers mentioned rehabilitation options, but specific information was lacking.
      Further long-term prospective research is essential, not only to determine the
      function impairment caused by the tumor and CRT, but also to assess the effects
      of known and newly developed rehabilitation measures. Therefore, in September
      2006, the Netherlands Cancer Institute started a randomised clinical trial (RCT):
      Prevention of trismus, swallowing and speech problems in patients treated with
      chemoradiotherapy for advanced head and neck cancer. This systematic review was
      carried out to collect the baseline information for the future outcomes of this
      RCT.

PMID- 18825401
TI  - Traumatic luxation of the nose in a newborn: case report and review of the
      literature.
AB  - During delivery the delicate structures of the face are predominantly exposed to
      external force effects and hence deformities on the nose can emerge as a birth
      related trauma in newborns. As self-straightening of the nasal septum commonly
      occurs, a conservative therapy is recommended for most cases. We report on a case
      where a birth-related trauma of the nose leaded to acute breathing problems in a
      newborn with insufficient oxygenation. An overview about the available literature
      is given. A cautious reposition of the nose proved to be an appropriate
      management for short- and long-term development.

PMID- 18825402
TI  - Expression of both oestrogen receptor alpha and beta in human skeletal muscle
      tissue.
AB  - There are two oestrogen receptors (ERs), ERalpha and ERbeta. ERbeta protein is
      expressed in human skeletal muscle in the nuclei of both myofibres and
      endothelial cells, whether ERalpha protein is present in this tissue is unknown.
      We studied the expression of ERalpha protein in human skeletal muscle biopsies
      taken from vastus lateralis from four men, four women, two children and two
      postmenopausal women. Immunohistochemistry was used to determine the proportions
      of nuclei that were positively stained for ERalpha, the proportion of ERalpha
      positive nuclei located in the muscle fibres and in capillaries and to test for
      possible co-expression of ERalpha and ERbeta. Both ERs were expressed in all
      subjects. Of all nuclei, 63% stained for ERalpha with no sex difference. ERalpha
      was localised both in myofibres and in endothelial cells of the capillaries, 25%
      of the ERalpha-positive nuclei were located in the capillaries. ERalpha and
      ERbeta were generally expressed in the same nuclei. The present study shows for
      the first time the expression of ERalpha protein in human skeletal muscle
      independently of age and sex. These results might improve understanding of the
      physiological role of oestrogen in human skeletal muscle and raise new questions
      about activation of ERs in skeletal muscle.

PMID- 18825404
TI  - Clinical utility of serum Interleukin-1 receptor antagonist levels as a
      diagnostic and prognostic assay in surgical patients.

PMID- 18825403
TI  - Molecular imaging with nanoparticles: giant roles for dwarf actors.
AB  - Molecular imaging, first developed to localise antigens in light microscopy, now
      encompasses all imaging modalities including those used in clinical care: optical
      imaging, nuclear medical imaging, ultrasound imaging, CT, MRI, and photoacoustic
      imaging. Molecular imaging always requires accumulation of contrast agent in the
      target site, often achieved most efficiently by steering nanoparticles containing
      contrast agent into the target. This entails accessing target molecules hidden
      behind tissue barriers, necessitating the use of targeting groups. For imaging
      modalities with low sensitivity, nanoparticles bearing multiple contrast groups
      provide signal amplification. The same nanoparticles can in principle deliver
      both contrast medium and drug, allowing monitoring of biodistribution and
      therapeutic activity simultaneously (theranostics). Nanoparticles with multiple
      bioadhesive sites for target recognition and binding will be larger than 20 nm
      diameter. They share functionalities with many subcellular organelles (ribosomes,
      proteasomes, ion channels, and transport vesicles) and are of similar sizes. The
      materials used to synthesise nanoparticles include natural proteins and polymers,
      artificial polymers, dendrimers, fullerenes and other carbon-based structures,
      lipid-water micelles, viral capsids, metals, metal oxides, and ceramics. Signal
      generators incorporated into nanoparticles include iron oxide, gadolinium,
      fluorine, iodine, bismuth, radionuclides, quantum dots, and metal nanoclusters.
      Diagnostic imaging applications, now appearing, include sentinal node
      localisation and stem cell tracking.

PMID- 18825405
TI  - The interconversion of ACC deaminase and D-cysteine desulfhydrase by directed
      mutagenesis.
AB  - Progress in DNA sequencing of plant genomes has revealed that, in addition to
      microorganisms, a number of plants contain genes which share similarity to
      microbial 1-aminocyclopropane-1-carboxylate (ACC) deaminases. These enzymes
      cleave ACC, the immediate precursor of ethylene in plants, into ammonia and alpha
      ketobutyrate. We therefore sought to isolate putative ACC deaminase cDNAs from
      tomato plants with the objective of establishing whether the product of this gene
      is a functional ACC deaminase. In the work reported here, it was demonstrated
      that the enzyme encoded by the putative ACC deaminase cDNA does not have the
      ability to break the cyclopropane ring of ACC, but rather it utilizes D: 
      cysteine as a substrate, and in fact encodes a D: -cysteine desulfhydrase.
      Kinetic characterization of the tomato enzyme indicates that it is similar to
      other, previously characterized, D: -cysteine desulfhydrases. Using site-directed
      mutagenesis, it was shown that altering only two amino acid residues within the
      predicted active site served to change the enzyme from D: -cysteine desulfhydrase
      to ACC deaminase. Conversely, by altering two amino acid residues at the same
      positions within the active site of ACC deaminase from Pseudomonas putida UW4 the
      enzyme was converted into D: -cysteine desulfhydrase. Therefore, it is possible
      that a change in these two residues may have occurred in an ancestral protein to
      result in two different enzymatic activities.

PMID- 18825406
TI  - An unidentified ultraviolet-B-specific photoreceptor mediates transcriptional
      activation of the cyclobutane pyrimidine dimer photolyase gene in plants.
AB  - Cyclobutane pyrimidine dimers (CPDs) constitute a majority of DNA lesions caused
      by ultraviolet-B (UVB). CPD photolyase, which rapidly repairs CPDs, is essential
      for plant survival under sunlight containing UVB. Our earlier results that the
      transcription of the cucumber CPD photolyase gene (CsPHR) was activated by light
      have prompted us to propose that this light-driven transcriptional activation
      would allow plants to meet the need of the photolyase activity upon challenges of
      UVB from sunlight. However, molecular mechanisms underlying the light-dependent
      transcriptional activation of CsPHR were unknown. In order to understand
      spectroscopic aspects of the plant response, we investigated the wavelength
      dependence (action spectra) of the light-dependent transcriptional activation of
      CsPHR. In both cucumber seedlings and transgenic Arabidopsis seedlings expressing
      reporter genes under the control of the CsPHR promoter, the action spectra
      exhibited the most predominant peak in the long-wavelength UVB waveband (around
      310 nm). In addition, a 95-bp cis-acting region in the CsPHR promoter was
      identified to be essential for the UVB-driven transcriptional activation of
      CsPHR. Thus, we concluded that the photoperception of long-wavelength UVB by UVB
      photoreceptor(s) led to the induction of the CsPHR transcription via a conserved
      cis-acting element.

PMID- 18825407
TI  - Helicase-like transcription factor exhibits increased expression and altered
      intracellular distribution during tumor progression in hypopharyngeal and
      laryngeal squamous cell carcinomas.
AB  - The helicase-like transcription factor (HLTF) belongs to the SWI/SNF family of
      proteins that use the energy from adenosine triphosphate hydrolysis to remodel
      chromatin during a variety of cellular processes. HLTF is also involved in DNA
      repair. Using computer-assisted microscopy, the immunohistochemical expression of
      HLTF was determined using a series of 100 hypopharyngeal and 56 laryngeal
      squamous cell carcinomas (SCCs) compared to tumor-free epithelia (60 cases) and
      dysplasias (92 cases). In hypopharyngeal SCC tumor progression, increased HLTF
      expression was associated with the percentage of immunopositive epithelial tissue
      areas (p = 0.02) and the staining intensity of the positive area (p = 0.0005). In
      the cases of laryngeal lesions, the immunolabeling intensity of HLTF
      significantly decreased with malignancy (p = 0.01). We also observed a
      significant shift of HLTF expression from the cytoplasm toward the nuclear
      compartment (p = 0.0007). Our data reveal an association between the presence of
      HLTF and neoplastic progression of hypopharyngeal and laryngeal SCCs.

PMID- 18825408
TI  - A novel role of serum cytochrome c as a tumor marker in patients with operable
      cancer.
AB  - PURPOSE: This study aimed to evaluate serum cytochrome c (cyto-c) levels as a
      novel role of tumor marker in patients with operable malignant tumors. METHODS:
      Serum cyto-c levels and lactate dehydrogenase (LD) activity were measured in a
      total of 257 cases (232 malignant and 25 benign). To identify the relationship
      between serum cyto-c and current tumor markers, six variables, such as gender,
      age, invasion, lymph node metastasis, distant metastasis, and LD, were analyzed
      by uni- and multivariate regression analysis methods. The test performance of
      serum cyto-c for the prediction of malignant behavior was evaluated by receiver
      operating characteristic (ROC) curves. RESULTS: The serum cyto-c level was
      significantly higher in patients with malignant tumors than patients with benign
      tumors (20.6 vs. 15.5 ng/mL; P = 0.017, Mann-Whitney U test). No difference in
      the levels among subtypes of cancer was found, indicating that the change in
      serum cyto-c levels reflect cancer individually and not specific subtypes of
      cancer. The survival in patients with serum cyto-c levels over 40 ng/mL was poor
      (Kaplan-Meier test, P < 0.0001, Hazard ratio 16.76, 95% confidential interval
      4.45-63.04). Multiple linear regression analyses disclosed the close association
      of serum cyto-c levels with invasion (P = 0.0004), metastasis (P = 0.0262) except
      for regional lymph node metastasis, and activity of serum LD (P < 0.0001), all of
      which are well known to represent malignant behavior. Conversely, the measurement
      of serum cyto-c was verified to have excellent diagnostic accuracy of 0.802 and
      0.781 for the detection of invasion and metastasis (the area under curves of the
      constructed ROCs). CONCLUSION: Serum cyto-c is a potent tumor marker as a
      predictor for malignant potential in cancers.

PMID- 18825409
TI  - Regulation of TLR4-induced IL-6 response in bladder cancer cells by opposing
      actions of MAPK and PI3K signaling.
AB  - PURPOSE: Toll-like receptor 4 (TLR4) was found to be aberrantly expressed in
      bladder cancer, inducing some genes expression and facilitating tumor
      progression. Recent data suggest that tumor associated Interleukin-6 (IL-6)
      correlates with tumor size and grade in bladder cancer. However, the molecule
      mechanisms of the induction of IL-6 response in bladder cancer cells are not well
      elucidated. In this study, we manage to find out whether TLR4 signaling is
      involved in the production of IL-6 by human bladder cancer cells, and the
      detailed molecule mechanisms by which IL-6 is up-regulated. METHODS: We selected
      human bladder cancer T24 cell line in the present study, and examined its
      expression of TLR4 and CD14 by using flow cytometry. TLR4 signaling was activated
      by lipopolysaccharide (LPS) and IL-6 secretion in culture supernatants was tested
      by using ELISA kit. The expression of p38, ERK, JNK and Akt were determined by
      western-blot analysis using specific antibodies. RESULTS: Our study demonstrated
      that CD14 and TLR4 were constitutively expressed in T24 cells and activation of
      TLR4 signaling by LPS resulted in phosphorylation of MAPK and PI3K pathways and
      up-regulation of IL-6 in dose- and time-dependent manner. Pretreatment of cells
      with SB203580 (inhibitor of p38) and PD98059 (inhibitor of ERK) attenuated LPS
      induced IL-6 expression, whereas LY294002 (inhibitor of PI3K) markedly amplified
      the LPS-stimulated synthesis of IL-6. CONCLUSIONS: Our results demonstrate that
      activation of TLR4 signaling in bladder cancer cells induces tumor-associated IL
      6 expression via activation of p38 and ERK, whereas activation of PI3K/Akt exerts
      an opposing action.

PMID- 18825410
TI  - Study on relationship between angiogenesis and micrometastases of peripheral
      blood in breast cancer.
AB  - PURPOSE: To investigate the relationship between microvessel density, expression
      of vascular endothelial growth factor A (VEGF-A) and micrometastases in
      peripheral blood of patients with breast cancer. METHOD: Microvessel density
      (MVD) and expression of VEGF-A were detected by immunohistochemistry S-P. Nested
      RT-PCR was introduced to detect the expression of hMAM mRNA in peripheral blood
      of all cases. RESULT: Average MVD was 28.95 +/- 6.95 microvessels/100x and
      positive rate of VEGF-A was 64.0% (32/50) in 50 cases with breast cancer. MVD
      count and expression of VEGF-A were related to tumor size, metastasis of axillary
      lymph nodes and clinical stages (P < 0.05), independent of age and histological
      classification (P > 0.05). The positive rate of hMAM mRNA in peripheral blood was
      34.0% (17/50), which correlated with lymphatic metastasis and clinical stages (P
      < 0.05), independent of pathological category, menopause and hormone receptor (P
      > 0.05). MVD count and positive rate of VEGF-A in breast cancer with positive
      expression of hMAM mRNA was obviously higher than those without hMAM mRNA
      expression (chi (2) = 5.766, P = 0.032; t = 5.37, P = 0.002). CONCLUSIONS: MVD
      count and positive expression of VEGF-A closely correlated to hMAM mRNA released
      from tumor cells in the circulation. hMAM mRNA is expected to become a valuable
      marker for further study on micrometastases of breast cancer.

PMID- 18825411
TI  - Four consecutive multicenter phase II trials of adjuvant chemoradiation in
      patients with completely resected high-risk gastric cancer: the experience of the
      German AIO/ARO/CAO group.
AB  - PURPOSE: Feasibility and efficacy of four different adjuvant radiochemotherapy
      regimens in patients with completely resected gastric cancer were evaluated in
      consecutive cooperative phase II trials using different 5-fluorouracil (5-FU)
      based combination chemotherapies (CTX) and 5-FU-enhanced radiotherapy. METHODS:
      Between 2000 and 2005, 157 patients with completely resected gastric
      adenocarcinoma were included. The study design was based on two cycles of CTX and
      irradiation with 45 Gy plus concomitant 5-FU 225 mg/m(2) per 24 h between these
      two cycles. CTX cycles consisted of 5-FU, folinic acid (FA), cisplatin plus
      paclitaxel (FLPP); 5-FU, FA and cisplatin (FLP); 5-FU, FA and irinotecan (FLI);
      or 5-FU, cisplatin plus docetaxel (FPD). RESULTS: Median follow-up for all four
      trials was 18 months (range, 1-64) without significant difference between the
      four regimens: FLPP 30 months (2-46+), FLP 18 months (1-64+), FLI 15 months (1
      26), FPD 10 months (5-19+). Treatment associated toxicity was tolerable and did
      not differ significantly between the four CTX regimens. Across all patients grade
      (3/4), toxicities during the first cycle/chemoradiation/second cycle consisted of
      leukocytopenia 4%/2%/30%, anorexia 5%/10%/6%, diarrhea 6%/1%/3%, nausea 2%/7%/2%.
      Early death occurred in one patient due to Pneumocystis carinii pneumonia. Median
      progression free survival was 23 months for FLPP, 18 months for FLP, 14 months
      for FLI, 9 months for FPD (not significant). One-year-overall survival rates were
      95% for FLPP, 82% for FLP, 94% for FLI, 86% for FPD. CONCLUSION: Adjuvant
      radiochemotherapy in patients with gastric cancer can be safely given continuous
      infusion of 5-FU at 225 mg/m(2) per day. In addition, a variety of 5-FU-based
      multiagent chemotherapy regimen with defined activity in gastric cancer appears
      both safe and effective when given prior and after radiochemotherapy in this
      setting.

PMID- 18825412
TI  - Control of aggressive fibromatosis by treatment with imatinib mesylate: a step
      forward?
AB  - Numerous studies referring to conventional chemotherapy for aggressive
      fibromatosis with the use of doxorubicin, cyclophosphamide, vincristin,
      vinblastine and other drugs have been published. Imatinib mesylate is a recently
      developed oral anticancer agent designed to selectively inhibit tyrosine kinases
      implicated in oncogenesis and it seems to represent a promising opportunity (also
      in first line) in the treatment of patients with advanced disease not candidate
      to prior surgery.

PMID- 18825413
TI  - Isolation and immunolocalization of a putative protective antigen (p26/23) from
      adult Haemonchus contortus.
AB  - The putative protective antigen, p26/23, from adult Haemonchus contortus was
      isolated. A soluble extract from adult helminths obtained from the abomasa of
      hyperinfected (12,000 infective larvae) female Manchego lambs and treated with a
      mixture of protease inhibitors was subjected to affinity chromatography
      (hexylgluthatione) to eliminate the enzyme gluthatione S-transferase. The eluate
      was analyzed by electrophoresis under denaturing and reducing conditions (sodium
      dodecyl sulfate polyacrylamide gel electrophoresis), electrotransferred to nylon
      membranes, and assayed by Western blot with sera from immunized lambs. The bands
      recognized by the lambs' sera corresponding to proteins with a molecular weight
      of 23-26 kDa (p26/23) were excised, eluted, and separated by reverse-phase
      chromatography. This allowed the isolation of a single protein, which was
      expressed in both infective larvae (L3) and the adult stage of the parasite. The
      first 20 amino acids of the N-terminal end of the purified protein were
      determined. The partial amino acid sequence revealed a 100% identity with the N
      terminus of one of the peptides present in the p26/23 immunoprotective fraction
      previously tested by us against sheep haemonchosis. No significant homology with
      any reported sequence was found except for the deduced sequence of a hypothetic
      H.contortus protein (HCC00515). Immunolocalization studies showed that the
      protein was expressed in the hypodermic chords of the nematode.

PMID- 18825414
TI  - Treatment and control of mycoplasma contamination in Plasmodium falciparum
      culture.
AB  - A comparative efficacy of four antibiotics, plasmocin (macrolid), Biomyc-1, -2,
      (tetracycline), and Biomyc-3, and Mycoplasma Removing Agent (quinolone
      derivatives) was determined for elimination of mycoplasma from Plasmodium
      falciparum culture. Presence of mycoplasma was detected using enzyme-PCR-based
      mycoplasma detection kit and survival of malaria parasite was determined in
      Giemsa's stained smear made from treated and untreated cultures. It was observed
      that a combination of Biomyc-1 and -2 killed malaria parasites within 24 h,
      whereas plasmocin and Biomyc-3 caused slow death of malaria parasite stretched
      over a period of 6 days. The only compound which did not kill malaria parasite
      and eradicated mycoplasma from P. falciparum culture was observed to be MRA.

PMID- 18825415
TI  - Isolation and characterization of conserved non-coding sequences among rice
      (Oryza sativa L.) paralogous regions.
AB  - Segmental duplication is particularly frequent within plant genomes and the
      ability of the original single-copy gene to gain a new function for the change of
      regulatory elements is one of the prominent consequences of duplication. Thus, it
      is important to study the pattern of conserved non-coding sequence (CNS) between
      paralogous genes. We report the result of a survey of CNSs among paralogous
      regions in rice (Oryza sativa L.), as well as the comparison of CNS dataset
      between rice and Arabidopsis thaliana. Some common properties, such as the change
      of A + T content near the CNS boundaries and CNS are enriched in regulatory
      genes, were observed. However, the content of CNSs differs between rice and
      Arabidopsis, and it is interesting that the rice metabolic network includes both
      CNS-poor and CNS-rich genes, which indicated a fine-tuned metabolic network
      presents in rice.

PMID- 18825416
TI  - Non-native earthworms in riparian soils increase nitrogen flux into adjacent
      aquatic ecosystems.
AB  - Riparian zones are an important transition between terrestrial and aquatic
      ecosystems, and they function in nutrient cycling and removal. Non-native
      earthworms invading earthworm-free areas of North America can affect nutrient
      cycling in upland soils and have the potential to affect it in riparian soils. We
      examined how the presence of earthworms can affect riparian nutrient cycling and
      nutrient delivery to streams. Two mesocosm experiments were conducted to
      determine how (1) the biomass of earthworms and (2) earthworm species can affect
      nutrient flux from riparian zones to nearby streams and how this flux can affect
      streamwater nutrients and periphyton growth. In separate experiments, riparian
      soil cores were amended with one of four mixed earthworm biomasses (0, 4, 10, or
      23 g m(-2) ash-free dry mass) or with one of three earthworm species
      (Aporrectodea caliginosa, Lumbricus terrestris, L. rubellus) or no earthworm
      species. Riparian soil cores were coupled to artificial streams, and over a 36
      day period, we measured nutrient leaching rates, in-stream nutrient
      concentrations, and periphyton growth. Ammonium leaching increased with
      increasing biomass and was greatest from the A. caliginosa treatments. Nitrate
      leaching increased through time and increased at a greater rate with higher
      biomass and from cores containing A. caliginosa. We suggest that the overall
      response of increased nitrate leaching [90% of total nitrogen (N)] was due to a
      combination of ammonium excretion and burrowing by earthworms, which increased
      nitrification rates. During both experiments, periphyton biomass increased
      through time but did not differ across treatments despite high in-stream
      inorganic N. Through time, in-stream phosphorus (P) concentration declined to <5
      microg l(-1), and periphyton growth was likely P-limited. We conclude that
      activities of non-native earthworms (particularly A. caliginosa) can alter
      biogeochemical cycling in riparian zones, potentially reducing the N-buffering
      capacity of riparian zones and altering stoichiometric relationships in adjacent
      aquatic ecosystems.

PMID- 18825417
TI  - Causes of reduced clutch size in a tidal marsh endemic.
AB  - We tested three hypotheses of clutch size variation in two subspecies of the
      swamp sparrow (Melospiza georgiana georgiana and M. g. nigrescens). Swamp
      sparrows follow the pattern of other estuarine endemics, where clutch size is
      smaller among tidal salt marsh populations (M. g. nigrescens) than their closest
      inland relatives (M. g. georgiana). Our results support predation risk and
      temperature, but not adult survival, as explanations of this pattern in swamp
      sparrows. Coastal nests were twice as likely to fail as inland nests, and
      parental activity around the nest site was positively related to clutch size at
      both sites. When brood size was controlled for, coastal adults visited nests less
      often and females vocalized less frequently during visits than inland birds,
      which may decrease nest detectability to predators. Coastal parents waited longer
      than inland birds to feed offspring in the presence of a model nest predator, but
      there was no difference in their response to models of predators of adults, as
      would be expected if coastal birds possessed increased longevity. Additionally,
      coastal females laid more eggs than inland females over a single season,
      following a within-season bet-hedging strategy rather than reducing within-season
      investment. Coastal territories experienced ambient air temperatures above the
      physiological zero of egg development more often, and higher temperatures during
      laying correlated with smaller clutches and increased egg inviability among
      coastal birds. Similar effects were not seen among inland nests, where laying
      temperatures were generally below physiological zero. Both subspecies showed an
      increase in hatching asynchrony and a decrease in apparent incubation length
      under high temperatures. Coastal individuals, however, showed less hatching
      asynchrony overall despite higher temperatures. Both air temperatures during
      laying and predation risk could potentially explain reduced clutch size in not
      only coastal plain swamp sparrows, but also other tidal marsh endemics.

PMID- 18825418
TI  - Impacts of cloud immersion on microclimate, photosynthesis and water relations of
      Abies fraseri (Pursh.) Poiret in a temperate mountain cloud forest.
AB  - The red spruce-Fraser fir ecosystem [Picea rubens Sarg.-Abies fraseri (Pursh)
      Poir.] of the southern Appalachian mountains, USA, is a temperate zone cloud
      forest immersed in clouds for 30-40% of a typical summer day, and experiencing
      immersion on about 65% of all days annually. We compared the microclimate,
      photosynthetic gas exchange, and water relations of Fraser fir trees in open
      areas during cloud-immersed, low-cloud, or sunny periods. In contrast to sunny
      periods, cloud immersion reduced instantaneous sunlight irradiance by 10-50%, and
      midday atmospheric vapor pressure deficit (VPD) was 85% lower. Needle surfaces
      were wet for up to 16 h per day during cloud-immersed days compared to <1 h for
      clear days. Shoot-level light-saturated photosynthesis (A (sat)) on both cloud
      immersed (16.0 micromol m(-2) s(-1)) and low-cloud (17.9 micromol m(-2) s(-1))
      days was greater than A (sat) on sunny days (14.4 micromol m(-2) s(-1)). Daily
      mean A was lowest on cloud-immersed days due to reduced sunlight levels, while
      leaf conductance (g) was significantly higher, with a mean value of 0.30 mol m(
      2) s(-1). These g values were greater than commonly reported for conifer tree
      species with needle-like leaves, and declined exponentially with increasing leaf
      to-air VPD. Daily mean transpiration (E) on immersed days was 43 and 20% lower
      compared to sunny and low-cloud days, respectively. As a result, daily mean water
      use efficiency (A/E) was lowest on cloud-immersed days due to light limitation of
      A, and high humidity resulted in greater uncoupling of A from g. Thus,
      substantial differences in photosynthetic CO2 uptake, and corresponding water
      relations, were strongly associated with cloud conditions that occur over
      substantial periods of the summer growth season.

PMID- 18825419
TI  - Optimal microbial adaptation routes for the rapid degradation of high
      concentration of phenol.
AB  - Pseudomonas fluorescence KNU417 was able to degrade up to 700 mg/L of phenol in
      65 h but could not degrade 1,000 mg/L of phenol. Phenol degradation rate was
      noticeably enhanced by pre-adaptation. In addition, the cell was able to degrade
      up to 1,300 mg/L of phenol by pre-adapting to 700 mg/L of phenol. Repeated
      adaptations to the same concentration of phenol showed negligible increase in
      degradation rate. Also, relatively low concentration of phenol (100-700 mg/L)
      required only one pre-adaptation while high concentration (1,000 mg/L) did two
      consecutive stepwise pre-adaptations for rapid degradation. Optimal adaptation
      routes were suggested for the fast phenol degradation. For example, 1,000 mg/L of
      phenol was degraded as fast as in 48 h when the cell was pre-adapted to 100 and
      300 mg/L of phenol sequentially. The mechanism of adaptation was explained in
      terms of catechol 1,2-dioxygenase induction, related to aromatic ring cleavage.

PMID- 18825420
TI  - Efficacy and safety of lisinopril for mild childhood IgA nephropathy: a pilot
      study.
AB  - Even in children with mild immunoglobulin (Ig)A nephropathy (IgA-N) showing
      minimal/focal mesangial proliferation, persistent proteinuria seems to be a risk
      factor for progression of the disease, indicating the need for an effective and
      safe treatment even in such cases. Studies carried out to date have indicated
      that angiotensin-converting enzyme inhibitors (ACEIs) reduce urinary protein
      excretion and preserve renal function in adult IgA-N. However, no prospective
      study of ACEI only for childhood IgA-N has yet been carried out. In this
      prospective single-arm pilot trial, we administered lisinopril (0.4 mg/kg per
      day) as therapeutic treatment to 40 children with mild IgA-N with proteinuria
      [morning urinary protein/creatinine ratio (uP/Cr) >or= 0.2 g/g]. Thirty-three
      patients reached the primary endpoint (uP/Cr < 0.2) during the 2-year treatment
      period. The cumulative disappearance rate of proteinuria determined by the Kaplan
      Meier method was 80.9%. Mean uP excretion was reduced from 0.40 to 0.18
      g/m(2)/day (p < 0.0001). Of the 40 patients treated, five (12.5%) showed
      dizziness, and four of these five needed the lisinopril dose reduced. However,
      lisinopril therapy was continued in all patients during the 2-year treatment
      period. No other side effect, such as cough, was observed. We conclude that the
      efficacy and safety of lisinopril is seemingly acceptable for the treatment of
      children with mild IgA-N.

PMID- 18825421
TI  - The efficacy and safety of palonosetron compared with granisetron in preventing
      highly emetogenic chemotherapy-induced vomiting in the Chinese cancer patients: a
      phase II, multicenter, randomized, double-blind, parallel, comparative clinical
      trial.
AB  - PURPOSE: This clinical trial was conducted to evaluate the efficacy and safety of
      Palonosetron in preventing chemotherapy-induced vomiting (CIV) among the Chinese
      cancer patients. PATIENTS AND METHODS: Two hundred and forty patients were
      scheduled to be enrolled and randomized to receive a single intravenous dose of
      palonosetron 0.25 mg, or granisetron 3 mg, 30 min before receiving highly
      emetogenic chemotherapy. The primary efficacy endpoint was the complete response
      (CR) rate for acute CIV (during the 0-24-h interval after chemotherapy).
      Secondary endpoints included the CR rates for delayed CIV (more than 24 h after
      chemotherapy). RESULTS: Two hundred and eight patients were accrued and received
      study medication. CR rates for acute CIV were 82.69% for palonosetron and 72.12%
      for granisetron, which demonstrated that palonosetron was not inferior to
      granisetron in preventing acute CIV. Comparisons of CR rates for delayed CIV
      yielded no statistical difference between palonosetron and granisetron groups and
      did not reveal non-inferiority of palonosetron to granisetron. Adverse events
      were mostly mild to moderate, with quite low rates among the two groups.
      CONCLUSIONS: A single dose (0.25 mg) of palonosetron is not inferior to a single
      dose (3 mg) of granisetron in preventing CIV and possesses an acceptable safety
      profile in the Chinese population.

PMID- 18825422
TI  - Changes in arbuscular mycorrhizal associations and fine root traits in sites
      under different plant successional phases in southern Brazil.
AB  - Fine root morphological traits and distribution, arbuscular mycorrhizal (AM)
      fungi, soil fertility, and nutrient concentration in fine root tissue were
      compared in sites under different successional phases: grass plants, secondary
      forest, and mature forest in Londrina county, Parana state, southern Brazil. Soil
      cores were collected randomly at the 0-10- and 10-20-cm depths in three quadrants
      (50 m2) in each site. Plants from the different successional stages displayed
      high differences in fine root distribution, fine root traits, and mycorrhizal
      root colonization. There were increases in the concentration of nutrients both in
      soil and fine roots and decrease of bulk soil density along the succession. The
      fine root biomass and diameter increased with the succession progress. The total
      fine root length, specific root length, root hair length, and root hair incidence
      decreased with the succession advance. Similarly, the mycorrhizal root
      colonization and the density of AM fungi spores in the soil decreased along the
      succession. Mycorrhizal root colonization and spore density were positively
      correlated with fine root length, specific root length, root hair length, root
      hair incidence, and bulk density and negatively correlated with fine root
      diameter and concentration of some nutrients both in soil and root tissues.
      Nutrient concentration in root tissue and in soil was positively correlated with
      fine root diameter and negatively correlated with specific root length, root hair
      length, and root hair incidence. These results suggest different adaptation
      strategies of plant roots for soil exploration and mineral acquisition among the
      different successional stages. Early successional stages displayed plants with
      fine root morphology and AM fungi colonization to improve the root functional
      efficiencies for uptake of nutrients and faster soil resource exploration. Late
      successional stages displayed plants with fine root morphology and mycorrhizal
      symbiosis for both a lower rate of soil proliferation and soil exploration
      capacity to acquire nutrients.

PMID- 18825423
TI  - Hematoma of the floor of the mouth and airway obstruction during mandibular
      dental implant placement: a case report.
AB  - BACKGROUND: Hematoma of the floor of the mouth during mandibular dental implant
      placement is a rare but potentially life-threatening complication. REPORT: A 53
      year-old man developed a hematoma of the floor of the mouth following a dental
      implant procedure, requiring admission to the hospital. SUMMARY: The floor of the
      mouth is richly vascularized by a number of branches of the submental and
      sublingual arteries. During a dental implant procedure in the anterior zone of
      the mandible, perforation of the lingual cortex may invade the floor of the mouth
      and therefore damage structures within the sublingual space. The anatomy of the
      lower portion of the anterior mandibular zone, with the mylohyoid ridge, makes it
      particularly vulnerable to this kind of injury, particularly in patients with
      atrophic mandibles. Only a few cases have been reported in the literature to
      date.

PMID- 18825424
TI  - Dynamics of alpha helix formation in the CSAW model.
AB  - We study the folding dynamics of polyalanine (Ala20), a protein fragment with 20
      residues whose native state is a single alpha helix. We use the CSAW model
      (conditioned self-avoiding walk), which treats the protein molecule as a chain in
      Brownian motion, with interactions that include hydrophobic force and internal
      hydrogen bonding. We find that large-scale structures form before small-scale
      structures, and obtain the relevant relaxation times. We find that helix
      nucleation occurs at two separate points on the protein chain, one near each end.
      The evolution of small- and large-scale structures involves different mechanisms.
      While the former can be described by rate equations that govern the growth of
      helical content, the latter is akin to the relaxation of an elastic solid.

PMID- 18825425
TI  - A 3D kinematic estimation of knee prosthesis using X-ray projection images:
      clinical assessment of the improved algorithm for fluoroscopy images.
AB  - In this paper, we propose three ideas to improve a kinematic estimation algorithm
      for total knee arthroplasty. The first is a two-step estimation algorithm that
      improves estimation accuracy by excluding certain assumptions needed for the
      pattern matching algorithm reported by Banks and Hodge. The second is
      incorporating a 3D geometric articulation model into the algorithm to improve
      estimation accuracy substantially for the depth translation, and to introduce
      contact points' trajectories between the articular surfaces. The third is an
      algorithm to process estimation even when the silhouettes of two components
      overlap. To assess our algorithm's potential for clinical application, we carried
      out two experiments. First, we used a robot to position the prosthesis.
      Estimation accuracy was checked by comparing input data to the robot with the
      estimates from X-ray photographs. Incorporating our articulation model remarkably
      reduced the error in the depth translation. Next, we performed a clinical
      assessment by applying the algorithm and articulation model to fluoroscopy images
      of a patient who had recently had TKA.

PMID- 18825426
TI  - Blood pressure waveform analysis by means of wavelet transform.
AB  - The assessment of cardiovascular function by means of arterial pulse wave
      analysis (PWA) is well established in clinical practice. PWA is applied to study
      risk stratification in hypertension, with emphasis on the measurement of the
      augmentation index as a measure of aortic pressure wave reflections. Despite the
      fact that the prognostic power of PWA, in its current form, still remains to be
      demonstrated in the general population, there is general agreement that analysis
      and interpretation of the waveform might provide a deeper insight in
      cardiovascular pathophysiology. We propose here the use of wavelet analysis (WA)
      as a tool to quantify arterial pressure waveform features, with a twofold aim.
      First, we discuss a specific use of wavelet transform in the study of pressure
      waveform morphology, and its potential role in ascertaining the dynamics of
      temporal properties of arterial pressure waveforms. Second, we apply WA to
      evaluate a database of carotid artery pressure waveforms of healthy middle-aged
      women and men. Wavelet analysis has the potential to extract specific features
      (wavelet details), related to wave reflection and aortic valve closure, from a
      measured waveform. Analysis showed that the fifth detail, one of the waveform
      features extracted applying the wavelet decomposition, appeared to be the most
      appropriate for the analysis of carotid artery pressure waveforms. What remains
      to be assessed is how the information embedded in this detail can be further
      processed and transformed into quantitative data, and how it can be rendered
      useful for automated waveform classification and arterial function parameters
      with potential clinical applications.

PMID- 18825427
TI  - The challenges for molecular nutrition research 4: the "nutritional systems
      biology level".
AB  - Nutritional systems biology may be defined as the ultimate goal of molecular
      nutrition research, where all relevant aspects of regulation of metabolism in
      health and disease states at all levels of its complexity are taken into account
      to describe the molecular physiology of nutritional processes. The complexity
      spans from intracellular to inter-organ dynamics, and involves iterations between
      mathematical modelling and analysis employing all profiling methods and other
      biological read-outs. On the basis of such dynamic models we should be enabled to
      better understand how the nutritional status and nutritional challenges affect
      human metabolism and health. Although the achievement of this proposition may
      currently sound unrealistic, many initiatives in theoretical biology and
      biomedical sciences work on parts of the solution. This review provides examples
      and some recommendations for the molecular nutrition research arena to move onto
      the systems level.

PMID- 18825430
TI  - Sensory loss, pains, motor deficit and axonal regeneration in length-dependent
      diabetic polyneuropathy.
AB  - In order to learn more on the occurrence of pains and motor deficit in severe
      diabetic polyneuropathy we reviewed the data of a series of 30 diabetic patients
      with an uncommonly severe length-dependent diabetic polyneuropathy (LDDP).
      Extensive sensory loss predominated with pains and temperature sensations and
      affected all four limb extremities, anterior trunk in all, plus the top of the
      scalp in 9 patients and the cauda equina territory in 2. Twenty patients had
      neuropathic pains. Symptomatic autonomic dysfunction was present in 28/30
      patients, mild distal motor deficit in 12 patients, severe in only one. Vibratory
      sensation was impaired in the lower limbs in 18 patients; position sense in 8. In
      the 10 nerve biopsy specimens, the density of myelinated axons was reduced to 23
      % and that of unmyelinated axons to 8.5 % of control values. Regenerating axons
      accounted for 32.4 +/- 19.8 % of the myelinated fibres. On teased fibre
      preparations 13.9 % of fibres were undergoing axonal degeneration, while 29.4 %
      of fibres showed focal abnormalities of the myelin sheath.We conclude that distal
      motor deficit occurs only after major loss of sensory fibres in LDDP; the
      unmyelinated axons are predominantly affected; absence of clinical improvement
      contrasts with the high proportion of regenerating axons; detection of alteration
      of pain and temperature sensation in the feet seems the best method for
      neuropathy screening in diabetic patients.

PMID- 18825431
TI  - No persistent effect of intravenous immunoglobulins in patients with narcolepsy
      with cataplexy.
AB  - We report on four patients with narcolepsy with cataplexy (NC), who were treated
      with high-dose intravenous immunoglobulins (IVIg). Although in some patients
      transient effects were seen of both objective (multiple sleep latency test and
      maintenance of wakefulness test) and subjective symptoms (Epworth Sleepiness
      Scale and frequency of cataplexy), these effects lasted at the most for a few
      weeks and did not persist. Our report challenges the recent observations of a
      favorable and persistent effect of IVIg in NC patients.

PMID- 18825432
TI  - Optical coherence tomography in multiple sclerosis: thickness of the retinal
      nerve fiber layer as a potential measure of axonal loss and brain atrophy.
AB  - BACKGROUND: Axonal distribution within the retinal nerve fiber layer (RNFL)
      measured by optical coherence tomography (OCT) correlates with axonal viability
      and integrity. OBJECTIVE: To investigate correlations between RNFL and MRI
      measures of axonal loss in MS patients. METHODS: Fifty one remitting-relapsing MS
      patients, 20 with a history of optic neuritis (MS-ON), 31 without optic neuritis
      (MS N-ON), and 12 healthy control subjects (HC) were included in the study. RNFL
      was measured by OCT and brain atrophy was assessed by MRI. RESULTS: The average
      RNFL in the affected eye (AE) in the MS-ON group was significantly lower than the
      RNFL in the MS N-ON (p = 0.01) and in HC (p = 0.01). The average RNFL in the
      unaffected eye (UE) and RNFL in MS N-ON were also lower than HC, but this value
      did not achieve significance. In MS N-ON a lower average RNFL was associated with
      an increased T1 lesion volume (p = 0.03) and T2-lesion volume (p = 0.001). The
      RNFL in MS N-ON was also associated with a reduction of BPF and %gm fraction (p =
      0.01, p = 0.02 respectively). In MS-ON there was a much weaker, non-significant
      correlation between RNFL thickness and T1, T2 volume, BPF, %gm and %wm fractions
      that might have resulted from a pronounced post-inflammatory local optic nerve
      atrophy in AE. CONCLUSION: The RNFL measured by OCT may be useful as a surrogate
      marker for assessment of brain atrophy in MS.

PMID- 18825433
TI  - Orbital apex lesion due to Aspergillosis presenting in immunocompetent patients
      without apparent sinus disease.
AB  - We present two cases in which Aspergillus infection was identified at a late
      stage in the clinical evaluation as the cause for a painful, progressive and
      indolent orbital apex syndrome in the absence of any clinical or radiological
      sign of sinus involvement. Surgical investigation was undertaken with serious
      subsequent morbidity. Although treatment is often satisfactory, neurological
      outcome is without exception poor. A review of the literature has revealed that
      the risk of such investigations is high, and advice is provided to readers which
      may allow avoidance of such complications in the future.

PMID- 18825434
TI  - Small cortical stroke in the "hand knob" mimics anterior interosseous syndrome.

PMID- 18825435
TI  - Slow vertical saccades in the frontotemporal dementia with motor neuron disease.
AB  - BACKGROUND: Ocular motor abnormalities play an important role in differential
      diagnoses of Pick complex diseases. OBJECTIVES: We evaluated how frequently
      supranuclear vertical saccadic impairment was observed in patients with
      frontotemporal dementia with motor neuron disease (FTD-MND). In addition, we
      tried to characterize their vertical saccadic abnormalities. MATERIALS AND
      METHODS: Eleven patients with FTD-MND were recruited. Supranuclear vertical
      saccadic impairment on gross examination was defined as slow saccades with or
      without reduction in the final amplitude of the movement accompanied by intact
      oculocephalic reflex. We also recorded their saccades in 6 out of 11 patients
      using 2-dimensional videooculography (VOG). We measured the amplitude and peak
      velocity of each saccade. RESULTS: On bedside examination, supranuclear vertical
      saccadic impairment was observed in 9 of 11 patients. One of the two remaining
      patients could not be evaluated due to poor cooperation and the other showed
      normal saccades. Five of nine patients with ocular abnormalities and one patient
      with normal saccade on gross examination underwent the VOG studies. The results
      showed that all the five patients with gross ocular abnormalities, compared with
      age-matched controls, had slowing of vertical saccades. Three out of five
      patients also showed slowing even in the large horizontal saccades. CONCLUSIONS:
      Our results showed that slow vertical saccades are common in FTDMND. FTD-MND
      could be another disease that affects vertical gaze among Pick complex disease.
      Future pathologic studies are needed to confirm the involvement of the burst
      neurons in the dorsal midbrain in patients with FTDMND.

PMID- 18825436
TI  - Diabetic uremic syndrome.

PMID- 18825437
TI  - Saccular function less affected than canal function in bilateral vestibulopathy.
AB  - Bilateral vestibulopathy (BV) is characterized by impaired or lost function of
      both labyrinths or eighth nerves. The diagnosis is routinely established by the
      head-thrust test, caloric irrigation and rotational testing with
      electronystagmography to determine the high- and low-frequency deficit of the
      vestibulo-ocular reflex. All three methods evaluate semicircular canal function
      only. Vestibular-evoked myogenic potentials (VEMPs) provide a measure of saccular
      otolith function. The aim of this study was to evaluate the frequency and extent
      of saccular dysfunction in patients with BV and to correlate saccular with
      horizontal semicircular canal dysfunction. A total of 84 BV-patients (23 females,
      mean age 62 +/- 15 (SD) years at the time of diagnosis assessment) were examined
      with VEMPs, electronystagmography with caloric irrigation and a standardized
      neuro-ophthalmological and -otological examination; 47 healthy subjects (18
      females, mean 56 +/- 19 years) served as controls. Amplitudes P1-N1 were
      significantly lower in patients with BV compared to controls (mean P1-N1 of all
      ears 82.1 +/- 50.7 microV in the patients vs. 130.8 +/- 85.9 microV in healthy
      volunteers). VEMPs were absent unilaterally in four patients with BV and in none
      bilaterally. In contrast, caloric responses were absent bilaterally in 40
      patients. There was no correlation between amplitude P1-N1 and caloric-induced
      nystagmus. The latencies P1 and N1 were not significantly different between
      patients and controls. Thus, in our study population saccular function appeared
      to be less affected than horizontal semicircular canal function.

PMID- 18825438
TI  - The OPTimization of interferon for MS study: 375 microg interferon beta-1b in
      suboptimal responders.
AB  - We aimed to evaluate the safety and MRI efficacy of interferon beta-1b (IFNbeta
      1b) 375 microg (subcutaneously [sc] every other day [eod]) in relapsing-remitting
      multiple sclerosis (RRMS) patients with a suboptimal response to IFNbeta-1b 250
      microg, i.e., with MRI activity or relapses. The OPTimization of Interferon for
      MS (OPTIMS) study was a prospective multicenter randomized phase 2 trial
      comprising a 6-month run-in phase (to identify suboptimal responders) and a 6
      month randomized phase of open-label clinical and blinded MRI follow-up. During
      run-in all patients were treated with IFNbeta-1b 250 microg sc eod; during the
      study phase suboptimal treatment responders were randomized either to IFNbeta-1b
      250 or 375 microg sc eod. Primary outcome was the proportion of patients without
      MRI activity during study Months 9-12 according to the intention-to-treat
      principle. 216 RRMS patients entered the study: 83 suboptimal responders were
      identified and randomized, 7 refused to continue treatment, 76 were included in
      the analysis. More patients treated with 375 microg had no MRI activity at Months
      9-12 (30/36 vs.16/40; relative risk, 0.28; 95 % confidence interval, 0.08-0.47; p
      = 0.0001). Sensitivity analysis ("worst case scenario") confirmed the results. No
      new or unexpected adverse events were observed, but there was a trend towards
      more withdrawals in the 375 microg group. Increasing the dose of IFNbeta-1b from
      250 microg to 375 microg is a successful strategy for reducing subclinical signs
      of disease activity in RRMS patients. Further studies are needed to show whether
      this dose may also improve clinical efficacy.

PMID- 18825439
TI  - Periventricular white matter hyperintensities increase the likelihood of
      progression from amnestic mild cognitive impairment to dementia.
AB  - BACKGROUND: White matter hyperintensities (WMH) have an effect on cognition and
      are increased in severity among individuals with amnestic mild cognitive
      impairment (aMCI). The influence of WMH on progression of aMCI to Alzheimer's
      disease (AD) is less clear. METHODS: Data were drawn from a three-year
      prospective, double blind, placebo controlled clinical trial that examined the
      effect of donepezil or vitamin E on progression from aMCI to AD. WMH from
      multiple brain regions were scored on MR images obtained at entry into the trial
      from a subset of 152 study participants using a standardized visual rating scale.
      Cox proportional hazards models adjusting for age, education and treatment arm
      were used to investigate the role of WMH on time to progression. RESULTS: 55 of
      the 152 (36.2 %) aMCI subjects progressed to AD. Only periventricular
      hyperintensities (PVH) were related to an increased risk of AD within three years
      (HR = 1.59, 95 % CI = 1.24 - 2.05, p-value < 0.001). Correcting for medial
      temporal lobe atrophy or the presence of lacunes did not change statistical
      significance. CONCLUSION: PVH are associated with an increased risk of
      progression from aMCI to AD. This suggests that PVH, an MRI finding thought to
      represent cerebrovascular damage, contributes to AD onset in vulnerable
      individuals independent of Alzheimer pathology.

PMID- 18825440
TI  - Second opinions and tertiary referrals in neurology: a prospective observational
      study.
AB  - BACKGROUND AND OBJECTIVE: The number of neurological second opinions (SO) and
      tertiary referrals (TR) is increasing. The main purpose of this study was to
      assess whether a day-care admission made a meaningful contribution to standard
      neurological outpatient care, for a wide range of second opinions and tertiary
      referrals. METHODS: All new patients attending an academic neurological day-care
      clinic in a 6-month period were investigated. Before admission, all previous
      medical correspondence and ancillary investigations were reviewed. On the day of
      admission, extensive time was available for clinical evaluation and additional
      ancillary investigations and an attempt was made to come to a final diagnosis.
      Demographic characteristics, duration of symptoms, patient satisfaction, new
      diagnoses and treatment consequences were studied. RESULTS: 300 patients (183 SO
      and 117 TR) were evaluated. In total 103 patients (35 %) received a new diagnosis
      (26 % SO vs. 48 % TR, p < 0.001) and 69 (67 %) of these had therapeutic
      implications. A new treatment advice was given to a total of 149 patients (50 %),
      which was similar in both groups (48 % vs. 53 %). Second opinions were considered
      medically less relevant than tertiary referrals (39 % vs. 64 %, p < 0.001). The
      number of new diagnoses differed largely between various diagnosis categories.
      Especially somatoform disorders and radicular syndromes were often newly
      diagnosed. CONCLUSION: A high number of second opinion and tertiary referral
      patients benefits from a day-care admission in a neurological outpatient clinic.
      Careful selection for referral of patients who will benefit from daycare
      admission may even enlarge the diagnostic and therapeutic yield.

PMID- 18825441
TI  - 19th International Symposium on the Autonomic Nervous System, Kauai, Hawaii,
      October 29-November 1, 2008. Abstracts.

PMID- 18825443
TI  - Assessment of organochlorine pesticide levels in Manadas Creek, an urban
      tributary of the Rio Grande in Laredo, Texas.
AB  - The Rio Grande is the natural boundary between the United States and Mexico from
      El Paso, Texas, to Brownsville, Texas. It supports about 12 million people on
      both sides of the border for municipal, agricultural, industrial, and
      recreational uses. The rapid population and economic growth along the border
      region has led to increased pollution in the Rio Grande, which has been linked to
      several border health issues associated with pesticide contamination. This
      project was initiated to assess the organochlorine pesticide levels in the water
      and sediments in Manadas Creek, an urban tributary of the Rio Grande located in
      north Laredo, Texas. Water and sediment samples were collected monthly during a 6
      month period from July to December of 2006 and analyzed using gas chromatography
      with an electron capture detector after extraction via a solid-phase
      microextraction technique. Among the water and sediment samples collected,
      several organochlorine pesticides including alpha-, beta-, and gamma
      hexachlorocyclohexane (HCH), heptachlor epoxide, endrin, and 4,4'-DDT were found
      in either the creek water or sediments. Analysis of variance results indicated
      that only gamma-HCH had significant variation in the creek water among the
      sampling periods. Comparison of results with previous findings showed the
      presence of higher levels of HCH isomers and much lower DDT concentrations in the
      present study.

PMID- 18825444
TI  - Heavy metal levels in marine mollusks from areas with, or without, mining
      activities along the Gulf of California, Mexico.
AB  - To assess the safety for human consumption of commercially important bivalves
      harvested from areas with or without mining activities, we compared the levels of
      heavy metals in mollusks collected from different coastal environments along the
      Gulf of California. We sampled the mussel Mytilus edulis and the clams
      Laevicardium elatum and Megapitaria squalida (June 2004) and the clam Chione
      californiensis (November 2006). Concentrations of cadmium, lead, nickel, zinc,
      iron, copper, and manganese in the soft tissue of the mollusks were measured by
      atomic absorption spectrophotometry. Based on dry weight, the highest average
      concentrations of iron, copper, and cadmium were found in clams from Loreto (572,
      181, and 4.66 mg/kg, respectively); that of nickel, in mussels from San Luquitas
      (12.2 mg/kg); that of zinc, both in mussels from San Luquitas and in clams from
      Golfo de Santa Clara (94.3 and 91.8 mg/kg, respectively); and those of lead and
      manganese in clams from the Golfo de Santa Clara (9.2 and 3.68 mg/kg,
      respectively). Although mollusks were taken from coastal areas of the Gulf of
      California, which are considered to be contaminated by mining activities, the
      heavy metals in the sediments apparently were in a chemical form that had low
      bioavailability for the bivalves feeding in those areas. The interplay of
      oceanographic conditions and the chemical composition of anthropogenic inputs
      into the environment is not well understood. Thus, these factors or their
      interaction could potentially result in increased concentration and
      bioavailability of such metals in areas without effluent generated by mining
      activities.

PMID- 18825445
TI  - Occurrence and distribution of chlorobenzenes in the Tonghui river of Beijing,
      China.
AB  - Eleven chlorobenzenes (CBs) in surface water and sediments of Tonghui River, a
      main urban drainage river of Beijing in China, were determined in October 2003,
      January 2004, and April 2006. CBs were widely detected and the summation
      operatorCB concentrations in water ranged from 89.9 to 6638.0 ng/L, with average
      values of 1902.8 ng/L in 2003, 2084.0 ng/L in 2004, and 1281.2 ng/L in 2006,
      respectively. The summation operatorCB concentrations in surficial sediments
      varied from 18.2 to 1827.7 ng/g dry weight (dw), with average values of 897.4
      ng/g dw in 2003, 653.4 ng/g dw in 2004, and 562.6 ng/g dw in 2006, respectively.
      Nonparametric statistical analysis (Mann-Whitney U test) showed that there were
      no statistically significant changes in summation operatorCB concentrations in
      either surface water or sediments over the period 2003-2006. The distribution
      pattern of CBs in the Tonghui River indicates that further effort is warranted in
      reducing local sources of contaminants. Additionally, the summation operatorCB
      levels in sediment samples were found to be dependent on total organic carbon
      contents.

PMID- 18825446
TI  - Toxicological responses of red-backed salamanders (Plethodon cinereus) to soil
      exposures of copper.
AB  - Copper (Cu) has widespread military use in munitions and small arms, particularly
      as a protective jacket for lead projectiles. The distribution of Cu at many US
      military sites is substantial and sites of contamination include habitats in and
      around military storage facilities, manufacturing, load and packing plants, open
      burning/open detonation areas, and firing ranges. Some of these areas include
      habitat for amphibian species, which generally lack toxicity data for risk
      assessment purposes. In an effort to ascertain Cu concentrations in soil that are
      toxic to terrestrial amphibians, 100 red-backed salamanders (Plethodon cinereus)
      were randomly sorted by weight, assigned to either a control soil or one of four
      treatments amended with copper acetate in soil, and exposed for 28 days.
      Analytical mean soil concentrations were 18, 283, 803, 1333, and 2700 mg Cu/kg
      soil dry weight. Food consisted of uncontaminated flightless Drosophila
      melanogaster. Survival was reduced in salamanders exposed to 1333 and 2700 mg/kg
      by 55% and 100%, respectively. Mortality/morbidity occurred within the first 4
      days of exposure. These data suggest that a Cu soil concentration of and
      exceeding 1333.3 +/- 120.2 mg/kg results in reduced survival, whereas hematology
      analyses suggest that a concentration of and exceeding 803.3 +/- 98.4 mg/kg might
      result in reduced total white blood cell count. No effects were observed at 283.3
      +/- 36.7 mg/kg.

PMID- 18825447
TI  - Polycyclic aromatic hydrocarbon composition of sediments in the Ria de Vigo (NW
      Spain).
AB  - Individual parent polycyclic aromatic hydrocarbons (PAHs) were identified and
      quantified in samples of recent sediments at 32 stations in the Ria de Vigo (NW
      Spain) and its adjacent shelf by high-performance liquid chromatography and a
      fluorescence detector. This area suffers the pressure of nearly 500,000
      inhabitants and includes a number of important marine organisms. The total
      concentration for the sum of the 13 PAHs quantified were in the range 28-3203
      ng/g. The highest concentrations were found near the city of Vigo, where marinas
      and dockyards as well as highways with a high traffic flow are established. Low
      PAH concentrations were determined in the outermost part of the estuary, far from
      the anthropogenic influence. PAH isomers concentration ratios were assessed,
      indicating that the main source of these compounds in the whole area is
      pyrolysis. When compared with the EACs, threshold effect level, and probable
      effect level values, only the samples from the inner part of the ria can
      occasionally present adverse biological effects due to the PAH concentrations.

PMID- 18825448
TI  - Multiple giant coronary artery aneurysms due to Kawasaki disease:
      electrocardiogram-gated 64-slice multidetector row computed tomography findings.

PMID- 18825449
TI  - What is the true frequency of carditis in acute rheumatic fever? A prospective
      clinical and Doppler blind study of 56 children with up to 60 months of follow-up
      evaluation.
AB  - BACKGROUND: This study aimed to evaluate prospectively clinical and
      echocardiographic findings of patients who had rheumatic fever with and without
      clinical features of cardiac involvement. METHODS: For this study, 56 consecutive
      patients (mean age, 11.4 years) with acute rheumatic fever diagnosed according to
      the 1992 modified Jones criteria were evaluated at diagnosis, after 3 and 6
      months, then at 2 and 5 years. All assessments were performed blindly and
      included physical and cardiac examination, electrocardiogram, chest X-ray, and
      two-dimensional color-flow Doppler echocardiography. RESULTS: Initial clinical
      carditis was observed for 27 patients (48.2%), all of whom had positive
      echocardiographic abnormalities. Echocardiographic abnormalities were observed in
      11 patients who had arthritis or chorea presentation without initial clinical
      carditis. Persistence of the abnormalities was observed at a late follow-up
      evaluation in 72.7% of the cases. Sydenham's chorea was present in 8 patients
      with clinical carditis and in 10 without this disorder, 8 of whom had
      echocardiographic abnormalities. CONCLUSION: Patients who had acute rheumatic
      fever without clinical signs of carditis showed acute and late follow-up
      echocardiographic abnormalities suggestive of cardiac involvement. Clinicians
      should be attentive for the presence of cardiac involvement among patients with
      chorea.

PMID- 18825450
TI  - Environmental shaping of ribosomal RNA nucleotide composition.
AB  - Ribosomal RNA (rRNA) is one of the most important macromolecules in the cell. It
      is well established that high-temperature environmental conditions destabilize
      rRNA, leading to a selection for G+C-rich stabilizing structures. Our knowledge
      about the nucleotide composition effect of other environmental conditions,
      however, is limited. In the present work, I addressed this by correlating the
      rRNA nucleotide composition to known environmental habitats for bacteria. The
      bacterial phyla Firmicutes, Actinobacteria, and Proteobacteria were chosen for in
      depth analyses due to the abundance of information available in the databases.
      Major differences in nucleotide composition were identified between these phyla.
      In addition to the G+C-->A+T gradients, a main gradient of G+A-->C+T was
      identified for Firmicutes, while a G+T-->A+C gradient was identified for
      Actinobacteria. With respect to correlation to environmental conditions, the
      Firmicutes showed a main structure of high G+C being correlated to thermophilic
      conditions, high A+T to anaerobic conditions, and high C+T to halophilic
      conditions. The main patterns detected for Firmicutes can be explained by
      structural stability for high G+C, chemical instability of G under aerobic
      conditions, and structural stability by purine/pyrimidine skew for halophilic
      conditions. On the contrary, the correlations for Actinobacteria cannot easily be
      explained by chemical and/or structural stability. This may indicate interference
      with factors not included in my work. Finally, I found a main correlation between
      high A+T and endosymbiosis for Proteobacteria. High A+T probably reflects
      adaptation to cell internal growth. Further support for environmentally driven
      nucleotide composition shaping was found and that polyphyletic bacteria were
      associated with the same environment/nucleotide correlations. My conclusion is
      that environmental conditions and habitats have a major effect on rRNA nucleotide
      composition but that the effects may differ between the bacterial phyla.

PMID- 18825451
TI  - Role of unilateral aderenalectomy in ACTH-independent macronodular adrenal
      hyperplasia.

PMID- 18825452
TI  - The use of CEEA 34 in stapled hemorrhoidectomy: suggested modifications in
      technique.

PMID- 18825453
TI  - Resection line involvement after gastric cancer surgery: clinical outcome in
      nonsurgically retreated patients.
AB  - PURPOSE: Resection line infiltration (RLI) after surgical treatment represents an
      unfavorable prognostic factor in advanced gastric cancer. We performed a
      retrospective analysis of 89 patients with resection line involvement who did not
      undergo reoperation. METHODS: On behalf of the Italian Research Group for Gastric
      Cancer, we present the characteristics and outcome of 89 patients who were
      submitted to surgical resection for gastric cancer from 1988 to 2001 and did not
      undergo reoperation because of disease extension or associated pathologies.
      RESULTS: RLI was significantly higher in patients with T4 tumors and diffuse
      histological type. Anastomotic leakages were observed in 4.8% of infiltrated
      esophageal resection margins, whereas 1.9% of infiltrated duodenal resection
      lines showed duodenal fistulas. Five-year overall survival of patients with RLI
      was 29%. Prognosis was not affected by RLI in early forms (100% 5-year survival);
      however, 5-year survival in T2 and T3 stages was significantly lower with respect
      to the same stages without residual tumor. The influence of RLI on prognosis was
      confirmed in N0 as well as in N1 and N2 patients. RLI also was an independent
      prognostic at multivariate analysis (odds ratio = 1.5; 95% confidence interval,
      1.08-2.08; P = 0.0144). CONCLUSIONS: RLI significantly affects long-term survival
      of advanced gastric cancer. The impact on prognosis is independent of lymph node
      involvement. Patients in good general condition for whom radical surgery is
      possible should be considered for reoperation.

PMID- 18825454
TI  - A pilot study on the role of T-tube in typhoid ileal perforation in children.
AB  - BACKGROUND: Ileostomy is usually performed for patients of typhoid intestinal
      perforation with poor general condition, but it is associated with significant
      morbidity. We have used the T-tube in such patients as an alternative to
      ileostomy. METHODS: This is a prospective evaluation of a cohort of children with
      proven typhoid intestinal perforation. Patients with multiple perforations and
      poor general condition were managed with a T-tube inserted into the bowel lumen
      after closing all distal perforations (group 3). They were compared with patients
      who had primary closure of perforation (group 1) or bowel resection (group 2) to
      determine the efficacy of the use of T-tube. RESULTS: The total number of
      patients for groups 1, 2, and 3 was 51, 4, and 12 (n = 67). The mean number of
      perforations for the three groups was 1, 3.5 +/- 0.58, and 4.25 +/- 0.97. The
      operation time for the three groups was 37.29 +/- 3.24, 59.25 +/- 3.09, and 59.17
      +/- 4.17 minutes, respectively. The T-tube was removed after 13.17 days. The mean
      duration of fistula at T-tube site to heal was 8.58 +/- 2.11 days. The overall
      follow-up period was 10.94 +/- 1.15 months and none of the patients with T-tube
      placement had features of intestinal obstruction. CONCLUSIONS: In children with
      multiple typhoid intestinal perforations and poor general condition, the use of T
      tube may be an effective management option.

PMID- 18825455
TI  - Retraction transaminitis: an inevitable but benign complication of laparoscopic
      fundoplication.
AB  - BACKGROUND: Transient transaminitis has been identified following laparoscopic
      abdominal surgery. However, the importance of posture, duration of surgery, and
      mechanical retraction in its etiology remain unclear. METHODS: Liver function was
      assessed preoperatively then at 8, 24, 48 and 72 h following laparoscopic surgery
      including the following procedures: Nissen fundoplication (LN: n = 10);
      cholecystectomy (LC: n = 10); inguinal herniorrhaphy (LH: n = 10); and
      gastrectomy (LG: n = 5). RESULTS: Aspartate aminotransferase (AST) levels in LN
      patients exhibited a rapid rise within 8 h, peaking at 48 h before returning
      toward baseline. In the LN group, AST levels were significantly higher at 8 h and
      24 hours compared to all other groups and compared to LG at 48 h and 72 h. At 6
      week follow-up all AST levels were normal. No significant differences were seen
      in other hepatic parameters, and no correlation between AST and duration of
      operation, gender, or age was identified. CONCLUSIONS: Antireflux surgery is
      associated with transaminitis related to hepatic retraction, which is independent
      of patient posture or duration of observation, and it resolves spontaneously with
      no clinical consequences.

PMID- 18825456
TI  - Biosequestering potential of Spirulina platensis for uranium.
AB  - The uranium sequestering potential of Spirulina platensis was studied in batch
      mode, and its equilibrium was established in approximately 60 minutes. It had
      maximum sorption at pH 4.0 to 4.5. Equilibrium data is well represented by the
      Langmuir isotherm model followed by the Freundlich and Redlich-Peterson models.
      The interference of other cations and anions in solution was found to decrease
      sorption of the uranium, suggesting a competition for sorption sites on S.
      platensis. The desorption results showed that sodium citrate solution is
      effective, with 83% of uranium being recovered through nondestructive means.

PMID- 18825457
TI  - Analysis of gene expression identifies differentially expressed genes and
      pathways associated with lymphatic dissemination in patients with adenocarcinoma
      of the esophagus.
AB  - INTRODUCTION: The presence of lymphatic dissemination is an important predictor
      of survival in esophageal adenocarcinoma (EA). The aim of this study was to
      discover a prognostic gene expression profile for lymphatic dissemination in EA
      and to identify genes and pathways that provide oncological insight in lymphatic
      dissemination. METHODS: Patients who had lymphatic dissemination (N = 55) were
      compared with patients without lymphatic dissemination (N = 22). Whole-genome
      oligonucleotide microarrays were used to evaluate the genetic signature of 77
      esophageal cancers. Multiple random validation was used to analyze the stability
      of the molecular signature and predictive power. Gene set enrichment analysis
      (GSEA) was applied to elucidate oncogenetic pathways. RESULTS: Lymphatic
      dissemination was correctly predicted in 75 +/- 14% of lymph node positive
      patients. The absence of lymphatic dissemination was correctly predicted in 41 +/
      23% of lymph-node-negative patients. Argininosuccinate synthetase (ASS) was
      selected for validation on the protein level because it was present in most
      prognostic signatures as well as the list of differentially expressed genes. ASS
      expression was lower (P = 0.048) in patients with lymphatic dissemination than in
      patients without. GSEA identified that arginine metabolism pathways and lipid
      metabolism pathways are related to less chance of developing lymphatic
      dissemination. DISCUSSION: The predictive profile does not outperform current
      clinical practice to predict the presence of lymphatic dissemination in patients
      with EA. Several genes, including ASS, and genetic pathways which are important
      in the development of lymphatic dissemination in EA, were identified.

PMID- 18825458
TI  - The cost-effectiveness of sentinel node biopsy in patients with intermediate
      thickness primary cutaneous melanoma.
AB  - BACKGROUND: The aim of this study was to determine the cost-effectiveness of wide
      excision (WEX) + sentinel node biopsy (SNB) compared with WEX only in patients
      with primary melanomas >/=1 mm in thickness. METHODS: A Markov model was
      populated with probabilities of disease progression and survival from the
      published literature. Costs were obtained from diagnostic-related group
      weightings and health outcomes were measured in quality-adjusted life years
      (QALYs). RESULTS: Base case analyses suggested that, over a 20-year timeframe,
      the mean total cost per patient receiving WEX only was AU $23,182 with 10.45 life
      years (LY) and 9.90 QALYs. The mean cost per patient for WEX + SNB was AU $24,045
      with 10.77 LY and 10.34 QALYs. The incremental cost effectiveness ratio for WEX +
      SNB was AU $2,770 per LY and AU $1,983 per QALY. CONCLUSION: WEX + SNB appears to
      offer an improvement in health outcomes (in both LYs and QALYs) with only a
      slight increase in cost.

PMID- 18825459
TI  - Predicting life expectancy and symptom relief following surgery for advanced
      malignancy.
AB  - BACKGROUND: We prospectively evaluated surgeons' ability to predict outcomes of
      life expectancy and symptom relief following major surgery for patients with
      advanced malignancies. METHODS: Fifty-seven patients with advanced malignancies
      were evaluated regarding major symptoms requiring a surgical intervention and
      followed until death or last contact. The patients' surgeons answered questions
      preoperatively and postoperatively, relating to issues such as estimated survival
      time and likelihood of symptom relief following surgery. We compared these
      estimates with patients' clinical outcomes and responses to a symptom
      questionnaire completed just prior to surgery, and 2 weeks, 6 weeks, and 3 months
      following surgery. RESULTS: Surgeons' preoperative estimates of patient survival
      agreed with survival outcomes. Preoperatively, surgeons accurately identified
      cases where a patient was expected to live less than 1 year without surgery (P <
      0.0001) and with surgery (P = 0.0342). Surgeons' preoperative estimates of the
      success of symptom improvement following surgery did not correlate in general
      with patients' self-assessments (P = 0.6454). Specifically, surgeons
      underestimated their success in symptom resolution. However, there were
      statistically significant differences between patients who were judged by
      surgeons postoperatively to have mild or no palliation compared with those with
      excellent (P = 0.0372) and good (P = 0.0203) palliation. CONCLUSION:
      Preoperatively, surgeons accurately estimated patients' survival time with
      surgery. Surgeons' postoperative estimates of success of symptom relief agreed
      with patients' self-assessments. Preoperatively, surgeons tended to underestimate
      their patients' symptom relief. Surgeons may wish to consider other criteria than
      their predictions for symptom relief in deciding whether a patient is a candidate
      for palliative surgery.

PMID- 18825460
TI  - Surgical approach and perioperative complications determine short-term outcomes
      in patients with insulinoma: results of a bi-institutional study.
AB  - BACKGROUND: Despite advancements in radiologic imaging and minimally invasive
      surgery, the evaluation and management of insulinomas is institution and surgeon
      dependent. Therefore, the reported surgical outcomes are highly variable. We
      compared the surgical management and outcomes of insulinomas between two
      international tertiary-care surgical units to better identify the best management
      as determined by short-term outcomes. METHODS: We performed a retrospective
      review of patients who underwent surgery for insulinomas over a 117-month period
      at UT Southwestern Medical Center in Dallas (UTSW) and Queen Mary Hospital in
      Hong Kong (QMHK). Data collected included imaging studies, operative procedure,
      complications, and outcomes. RESULTS: Thirty-seven patients were identified.
      Preoperative localization by computed tomography (CT) scan was successful in 21
      patients (63.9%). In Hong Kong, 16 patients underwent selective arterial
      cannulation and calcium stimulation (SACST) with a success rate of 87.5%.
      Surgical management consisted of enucleation in 24 patients and distal
      pancreatectomy in 13 patients. Thirty patients underwent a concurrent
      intraoperative ultrasound, with localization in 96.7%. Laparoscopic procedures
      were accomplished in 20 patients. Nine postoperative complications were
      identified, four occurring in the laparoscopic group. Patients undergoing
      laparoscopic procedures had a decreased length-of-stay (LOS) compared with
      patients undergoing an open procedure and patients who had uncomplicated surgery
      had a trend toward decreased LOS. CONCLUSION: Though the accuracy of CT scans for
      localizing insulinomas is only 64%, the addition of SACST or intraoperative
      ultrasound and pancreatic palpation increases accuracy to 97.1%. Compared with
      open procedures, laparoscopic resection is associated with comparable
      complication rates and shorter hospital length of stay.

PMID- 18825461
TI  - Positive sentinel lymph nodes are a negative prognostic factor for survival in T1
      2 oral/oropharyngeal cancer-a long-term study on 103 patients.
AB  - BACKGROUND: To evaluate prognostic value of sentinel node biopsy (SNB) in
      oral/oropharyngeal squamous cell cancer (OOSCC) concerning overall/disease-free
      survival. METHODS: One hundred three consecutive patients with T1-2N0 OOSCC were
      consecutively recruited for SNB as single invasive staging method for the neck.
      Two hundred seventy-three sentinel nodes (SNs) were removed (mean, 2.65 per
      patient). Nine patients had 10 positive SNs (upstaging rate, 8.7%) found in
      levels I to III, leading to a therapeutic neck dissection. RESULTS: Mean
      observation time of all patients was 6.7 years; mean survival time of patients
      with negative or positive SNs was 6.9 and 3.7 years, respectively. There has been
      no false-negative result of SNB to date becoming manifest in ipsilateral node
      metastasis during follow-up. Five-year overall/disease-free survival of all
      patients was 82%/72%, respectively. The same parameters for the patients with
      negative SNs were 85%/74%, for those with positive SNs 38%/47%, respectively
      (statistically significant). There has been a higher statistical risk for
      locoregional recurrence for patients with positive SNs. Rates of metachronous
      second primary tumors developing during follow-up were 10.6% (negative SNs) and
      44.4% (positive SNs). CONCLUSION: SNB was a valuable diagnostic method in
      patients with T1-2N0 OOSCC avoiding elective neck dissections. Patients with
      positive SNs had statistically significantly higher rates of locoregional
      recurrences, second primary tumors, tumor-related deaths, and a worse
      overall/disease-free survival. To date, no therapeutic consequences in case of a
      positive SN beyond execution of modified radical neck dissection (to remove other
      positive nodes) and closer attention during follow-up can be concluded from this
      study.

PMID- 18825462
TI  - A periodic Droop model for two species competition in a chemostat.
AB  - Both uniform persistence and the existence of periodic coexistence state are
      established for a periodically forced Droop model on two phytoplankton species
      competition in a chemostat under some appropriate conditions. Numerical
      simulations using biological data are presented as well to illustrate the main
      result.

PMID- 18825463
TI  - First passage time analysis of animal movement and insights into the functional
      response.
AB  - Movement plays a role in structuring the interactions between individuals, their
      environment, and other species. Although movement models coupled with empirical
      data are widely used to study animal distribution, they have seldom been used to
      study search time. This paper proposes first passage time as a novel approach for
      understanding the effect of the landscape on animal movement and search time. In
      the context of animal movement, first passage time is the time taken for an
      animal to reach a specified site for the first time. We synthesize current first
      passage time theory and derive a general first passage time equation for animal
      movement. This equation is related to the Fokker-Planck equation, which is used
      to describe the distribution of animals in the landscape. We illustrate the first
      passage time method by analyzing the effect of territorial behavior on the time
      required for a red fox to locate prey throughout its home range. Using first
      passage time to compute search times, we consider the effect of two different
      searching modes on a functional response. We show that random searching leads to
      a Holling type III functional response. First passage time analysis provides a
      new tool for studying how animal movement may influence ecological processes.

PMID- 18825464
TI  - Percutaneous microwave ablation of liver cancer adjacent to the gastrointestinal
      tract.
AB  - PURPOSE: The purpose of the study was to prospectively evaluate safety and
      effectiveness of percutaneous microwave ablation under temperature monitoring
      assisted with ethanol injection for liver cancer abutting gastrointestinal tract.
      MATERIALS AND METHODS: One hundred seventy-nine hepatic tumors that underwent
      percutaneous microwave ablation with curative intention were included. Fifty
      three lesions located less than 5 mm from gastrointestinal tract were in
      gastrointestinal group. One hundred twenty-six lesions located more than 5 mm
      from hepatic surface and first or second branch of hepatic vessels were in
      control group. The temperature of marginal ablation tissue proximal to
      gastrointestinal tract was monitored and controlled to fluctuating between 45
      degrees C and 58 degrees C for more than 10 min for tumors in the
      gastrointestinal group. Ethanol (2-27 ml) was injected into marginal tissue in 33
      of 53 lesions of the GI group. RESULTS: Forty-seven of 53 tumors (88.7%) in the
      gastrointestinal group and 116 of 126 tumors (92.1%) in the control group
      achieved complete ablation (p > 0.05). There were neither immediate nor
      periprocedural complications in both groups. Tumor seeding happened in one of the
      gastrointestinal group and two of the control group. There was no delayed
      complication of bile ducts injury. CONCLUSION: Under strict temperature
      monitoring, microwave ablation assisted with ethanol injection is safe and
      achieves a high complete ablation rate for hepatic tumors adjacent to
      gastrointestinal tract.

PMID- 18825465
TI  - Button-loop feeding jejunostomy.
AB  - INTRODUCTION: Post-pyloric feeding via a surgical jejunostomy allows for enteral
      nutrition in patients that cannot receive oral or gastric feeding. Regardless of
      the technique used to create a jejunostomy, complications such as tube
      dislodgement, jejunostomy closure, or bowel obstruction can occur. SURGICAL
      TECHNIQUE: We present a simple and efficient jejunostomy technique that does not
      require a sewn anastomosis and employs an easily exchangeable feeding button.

PMID- 18825466
TI  - Routine liver biopsy to screen for nonalcoholic fatty liver disease (NAFLD)
      during cholecystectomy for gallstone disease: is it justified?
AB  - BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) and gallstone disease (GD)
      share common risk factors. There are no firm recommendations regarding screening
      of NAFLD in patients at risk. Our aim was to assess the prevalence of and factors
      associated with NAFLD in a cohort of patients operated for symptomatic GD and
      evaluate the usefulness of routine liver biopsy. METHODS: Ninety-five consecutive
      patients underwent a liver biopsy at the end of a standard laparoscopic
      cholecystectomy for symptomatic GD. Clinical, biochemical, demographic, and
      anthropometric variables were obtained prospectively. RESULTS: Fifty-two patients
      (55%) had biopsies compatible with NAFLD. These patients were classified
      according to the system proposed by Brunt et al. as follows: grade I, n = 27
      (52%); grade II, n = 15 (29%); grade III, n = 10 (19%). Two grade III patients
      had zone III focal perisinusoidal fibrosis and three had overt cirrhosis. Only
      13% of subjects had a suspected diagnosis of NAFLD preoperatively. In
      multivariate logistic regression, only obesity was significantly associated with
      NAFLD. There were no complications or mortality. DISCUSSION: Fifty-five percent
      of patients with GD have associated NAFLD. Awareness of this association may
      result in an earlier diagnosis. The high prevalence of NAFLD in patients with GD
      may justify routine liver biopsy during cholecystectomy to establish the
      diagnosis, stage, and possible direct therapy.

PMID- 18825467
TI  - Building better teams in surgery.
AB  - This manuscript represents an overview of a presentation at the SSAT 49th annual
      meeting which describes the evolution of the author's work within surgery to
      build and advance teamwork into processes of care.

PMID- 18825468
TI  - Biliogastric diversion for the management of high-output duodenal fistula: report
      of two cases and literature review.
AB  - High-output duodenal fistula occurs as a result of a duodenal wall defect caused
      by gastroduodenal surgery, endoscopic sphincterotomy, duodenal injury, and tumors
      with high morbidity and mortality rate. A new technique for its management is
      reported along with literature review. This procedure consists of transection of
      the duodenum 2 cm distally to the pylorus, transection of the common bile duct,
      and end duodenostomy with or without suturing the duodenal wall defect. The
      continuity of the alimentary tract is reinstated by an end-to-end
      duodenojejunostomy, end-to-side choledochojejunostomy, and end-to-side Roux-en-Y
      jejunojejunostomy, obtaining biliogastric diversion from the duodenum and closure
      of the fistula. This technique was performed in two patients with excellent
      results.

PMID- 18825469
TI  - A one-wire method for anatomic reduction of tibial fractures with Ilizarov frame.
AB  - Traditional external fixator techniques do not always correct minor residual
      malalignment. We asked whether using a one-wire method that corrects minor
      malalignment with an olive traction wire placed in the plane of the deformity
      allowed (1) uniform healing, (2) proper alignment, and (3) adequate reduction of
      fracture gaps. We retrospectively evaluated 72 patients in whom we used closed
      tibial fracture reduction using a circular external frame. We identified the
      plane of the residual deformity after alignment on a traction table using a C
      arm. In this plane, the final correction was performed with traction through an
      olive wire. Satisfactory alignment (less than 3 degrees deviation from normal)
      was obtained in 68 of the 72 patients (94%), and satisfactory reduction (gaps
      less than 2 mm) attained in 51 (71%). In no case was the fracture site opened
      surgically. Four patients underwent additional alignment correction with conical
      washers outside the operating room but no other efforts were needed to obtain
      further reduction after the initial surgery. Fractures healed in an average of 20
      weeks. We observed no major infections. The Ilizarov frame has been a valuable
      tool to achieve alignment and anatomic or near anatomic reduction of closed
      tibial fractures. LEVEL OF EVIDENCE: Level IV, therapeutic study. See the
      Guidelines for Authors for a complete description of levels of evidence.

PMID- 18825470
TI  - Rotational position of femoral and tibial components in TKA using the femoral
      transepicondylar axis.
AB  - Proper femoral and tibial component rotational positioning in TKA is critical for
      outcomes. Several rotational landmarks are frequently used with different
      advantages and limitations. We wondered whether coronal axes in the tibia and
      femur based on the transepicondylar axis in the femur would correlate with
      anteroposterior deformity. We obtained computed tomography scans of 100 patients
      with arthritis before they underwent TKA. We measured the posterior condylar
      angle on the femoral side and the angle between Akagi's line and perpendicular to
      the projection of the femoral transepicondylar axis on the tibial side. On the
      femoral side, we found a linear relationship between the posterior condylar angle
      and coronal deformity with valgus knees having a larger angle than varus knees,
      ie, gradual external rotation increased with increased coronal deformity from
      varus to valgus. On the tibial side, the angle between Akagi's line and the
      perpendicular line to the femoral transepicondylar axis was on average
      approximately 0 degrees , but we observed substantial interindividual variability
      without any relationship to gender or deformity. A preoperative computed
      tomography scan was a useful, simple, and relatively inexpensive tool to identify
      relevant anatomy and to adjust rotational positioning. We do not, however,
      recommend routine use because on the femoral side, we found a relationship
      between rotational landmarks and coronal deformity.

PMID- 18825471
TI  - Exercise, fitness, and neurocognitive function in older adults: the "selective
      improvement" and "cardiovascular fitness" hypotheses.
AB  - BACKGROUND: Although basic research has uncovered biological mechanisms by which
      exercise could maintain and enhance adult brain health, experimental human
      studies with older adults have produced equivocal results. PURPOSE: This
      randomized clinical trial aimed to investigate the hypotheses that (a) the
      effects of exercise training on the performance of neurocognitive tasks in older
      adults is selective, influencing mainly tasks with a substantial executive
      control component and (b) performance in neurocognitive tasks is related to
      cardiorespiratory fitness. METHODS: Fifty-seven older adults (65-79 years)
      participated in aerobic or strength-and-flexibility exercise training for 10
      months. Neurocognitive tasks were selected to reflect a range from little (e.g.,
      simple reaction time) to substantial (i.e., Stroop Word-Color conflict) executive
      control. RESULTS: Performance in tasks requiring little executive control was
      unaffected by participating in aerobic exercise. Improvements in Stroop Word
      Color task performance were found only for the aerobic exercise group. Changes in
      aerobic fitness were unrelated to changes in neurocognitive function.
      CONCLUSIONS: Aerobic exercise in older adults can have a beneficial effect on the
      performance of speeded tasks that rely heavily on executive control. Improvements
      in aerobic fitness do not appear to be a prerequisite for this beneficial effect.

PMID- 18825472
TI  - Variables related to utility in patients with ankylosing spondylitis.
AB  - The objective of this study was to identify variables associated to the utility
      of the health states in patients with ankylosing spondylitis (AS). A cross
      sectional study was performed in a tertiary care centre. AS patients (New York
      modified criteria) were included. Demographic and disease-related variables were
      collected. The social tariffs of the EuroQol-5D (EQ-5D) were used to obtain
      utility values. Univariate and multivariate regression analyses were used in
      order to identify variables associated with utility. Seventy patients, 52 male
      (74.3%), with age (mean +/- SD) 43.7 +/- 9.1 years and disease duration 10.8 +/-
      8.1 years, were included. The mean utility was 0.5625 +/- 0.3364. In the
      univariate analysis, patient global assessment, Bath Ankylosing Spondylitis
      Disease Activity Index (BASDAI) and Bath Ankylosing Spondylitis Functional Index
      (BASFI) had a good correlation with the EQ-5D values (Pearson's product moment
      correlation coefficient r > 0.6) whereas physician global assessment, patient
      pain assessment, and cervical rotation had a moderate correlation with the EQ-5D
      (0.6 > r > 0.4). Patients with significant comorbidity had lower utility values
      (0.3563 +/- 0.068) than those without it (0.6796 +/- 0.041, p = 0.0001). In the
      multivariate analysis, BASFI and BASDAI kept an independent association with
      utility and they explained a 62% of the variance of the utility values. In this
      study, physical function and disease activity, two outcomes with good
      responsiveness to the treatment, were the main determinants of the utility of the
      health states in AS patients.

PMID- 18825473
TI  - A case of Takayasu arteritis complicated by Castleman's disease.
AB  - We describe the first case of Takayasu Arteritis (TA) complicated by multicentric
      hyaline-vascular type of Castleman's disease (CD) which was diagnosed by the
      biopsy of mediastinal lymphnode 23 years after the diagnosis of TA. CD is
      classified as a lymphoid disorder of immune regulation characterized by a
      systemic, unregulated B cell proliferation, and there are some reports about the
      coincidence of CD and autoimmune diseases. This case has allowed us to gain some
      insight into a possible relation between the two disorders.

PMID- 18825474
TI  - Expression of receptor activator of nuclear factor -kappaB ligand, receptor
      activator of nuclear factor -kappaB, and osteoprotegerin, following low-level
      laser treatment on deproteinized bovine bone graft in rats.
AB  - The aim of this study was to investigate by immunohistochemistry the effects of
      low-level laser (LLL) irradiation on the expression of the receptor activator of
      nuclear factor -kappaB ligand (RANKL), osteoprotegerin (OPG), and the receptor
      activator of nuclear factor -kappaB (RANK) in deproteinized bovine bone grafts in
      rats. Twenty-four male Sprague-Dawley rats aged 15 weeks were allocated to either
      an experimental group that underwent LLL irradiation during bone healing at the
      bone graft sites of the rats' calvarial bone defects or a control group. In the
      experimental group, gallium-aluminum-arsenide (Ga-Al-As) diode LLL (wavelength
      808 nm; output 96 mW) was used to irradiate three areas on and around bone
      defects. The radiation was administered by the contact method for 10 s at 8.3
      J/cm(2), once a day for 7 days. The total dose over the complete schedule was
      40.32 J. The animals were killed on days 7, 14 or 21. The results of
      immunohistochemical analysis showed that the expression of RANKL (P = 0.199), OPG
      (P = 0.035), and RANK (P = 0.020) in the experimental group significantly
      increased from day 7, with a more even distribution than in the control group,
      and that this difference prevailed until the end of the experiment. Bone density
      of the experimental group after trichrome staining was also higher than in the
      control group. These results suggest that LLL irradiation facilitates bone
      metabolism during bone healing at the sites of deproteinized bovine bone grafts
      in rats.

PMID- 18825475
TI  - Smooth muscle tumour of the right groin: description of a unique case.
AB  - INTRODUCTION: A deep soft tissue smooth muscle tumour is a rare entity with few
      cases described in the literature. MATERIALS AND METHODS: Herein, we report a
      case of a smooth muscle tumour of the right inguinal area which presented as a
      painful mass. This case is unique because of the anatomic location of the tumour,
      which has not been reported before, and the clinical presentation of this tumour
      mimicked a hernia. CONCLUSION: Smooth muscle tumours in the inguinal area are an
      exceptionally rare occurrence, but clinicians should always consider less routine
      causes for a painful inguinal mass.

PMID- 18825476
TI  - Elevated blood pressure in overweight and obese Irish children.
AB  - BACKGROUND: The Irish childhood obesity epidemic, one of the highest ranking
      internationally, represents a major threat to public health. We sought to perform
      a retrospective observational study of a clinic based cohort of obese Irish
      children. METHODS: Clinical data relating to gender, age, height, weight, body
      mass index and blood pressure were analysed, from 206 children referred to a
      paediatric endocrine referral centre over a 15-year period for assessment of
      obesity. RESULTS: Younger patients tended to have a higher standardised body mass
      index at initial presentation; 92% of boys and 96% of girls referred were obese
      (age-related BMI >/= 95th percentile). Boys (51%) and girls (49%) had initial
      blood pressure measurements in the hypertensive range. There was a correlation
      between the degree of obesity and systolic blood pressure, particularly in boys.
      CONCLUSIONS: Obese Irish children present with significant long-term health
      risks, including hypertension at baseline.

PMID- 18825477
TI  - Vasoactive intestinal polypeptide secreting pancreatic tumour with hepatic
      metastases: long term survival after orthotopic liver transplantation.
AB  - BACKGROUND: VIPomas are rare neuroendocrine tumours, with metastases often
      confined to the liver. Orthotopic liver transplantation may be considered in
      patients with metastases confined to the liver, however the long term benefits
      have yet to be shown. AIMS: To discuss the role of orthotopic liver
      transplantation for neuroendocrine tumours including VIPomas. METHODS: We
      describe the case of a very rare pancreatic VIPoma, the therapeutic modalities
      employed, including orthotopic liver transplantation, and present the results of
      a relevant literature search. RESULTS: This case is the longest (25 years)
      reported in the literature for survival from a VIPoma after initial diagnosis and
      long term survival after liver transplantation (9 years). CONCLUSION: Liver
      transplantation for metastatic VIPomas confined to the liver may be justified in
      selected patients to provide symptomatic hormonal control and pain from tumour
      bulk, provided there is no extra hepatic disease and medical treatment has been
      exhausted.

PMID- 18825478
TI  - Prevalence of smoking among bar workers prior to the Republic of Ireland
      smokefree workplace legislation.
AB  - BACKGROUND: This study establishes baseline prevalence of smoking and cigarette
      consumption among Cork bar workers prior to the Republic of Ireland's (ROI)
      smokefree workplace legislation and compares gender- and age-specific smoking
      rates and estimates the adjusted odds of being a smoker for Cork bar workers
      relative to the general population. METHODS: Cross-sectional random sample of bar
      workers in Cork city and cross-sectional random telephone survey of the general
      population were conducted prior to the smokefree legislation. RESULTS: Self
      reported smoking prevalence among Cork bar workers (n = 129) was 54% (58% using
      cotinine-validated measures), with particularly high rates in women (70%) and 18
      28 years old (72%). Within the ROI (n = 1,240) sub-sample rates were
      substantially lower at 28%. Bar workers were twice as likely to be smokers as the
      general population sub-sample (OR = 2.15). CONCLUSIONS: Cork bar workers
      constitute an occupational group with an extremely high smoking prevalence.

PMID- 18825479
TI  - Darbepoetin in the control of cancer-related anaemia.
AB  - A group of 62 patients with different advanced cancers and with an anaemic
      condition were treated with a short course of darbepoetin administered on two
      different schedules as supportive therapy. The response rates (i.e. a haemoglobin
      increase of at least 1 g in 1 month) were 45.7% overall, 52.3% with weekly
      administration and 39% with 3-weekly administration. Darbepoetin activity was
      higher in men than in women, in younger patients than in older patients and in
      moderately anaemic patients than in severely anaemic patients, but these
      differences were not significant. Darbepoetin administration appears to be useful
      in rapidly reversing anaemia related to advanced cancer. However, the results
      reported in the literature for alpha-erythropoietin remain more appealing.

PMID- 18825480
TI  - Viral pathogens in acute exacerbations of chronic obstructive pulmonary disease.
AB  - The objective of this study is to determine the prevalence of respiratory
      syncytial virus (RSV) and other viral respiratory pathogens in emergency
      department (ED) patients with acute exacerbations of chronic obstructive
      pulmonary disease (AECOPD). COPD patients presenting to the ED with <10 days of
      AECOPD symptoms were eligible. We used PCR to test nasal swabs for common viral
      respiratory pathogens. We completed viral studies on 76 patients from two EDs.
      Patients had a mean age of 72 years, and were 68% male, 99% white, and 29%
      current smokers. Influenza vaccination was reported by 87%. Viruses were detected
      in 19 of 76 patients (25%). These included RSV A (2) and B (4); parainfluenza 1
      (1), 2 (0), and 3 (2); influenza A (3) and B (0); rhinovirus (4); and human
      metapneumovirus (3). A putative viral etiology was identified in 25% of AECOPD
      presenting for emergency care, of which approximately one-third were RSV-related.

PMID- 18825481
TI  - Genetic and phenotypic characterization of a low-pathogenicity avian influenza
      H11N9 virus.
AB  - An H11N9 low-pathogenicity avian influenza virus, A/duck/WA/663/97, was isolated
      from a sick Mandarin duck kept in an outdoor bird exhibit. Genetic and phenotypic
      characterization of the virus suggested that it originated from free-flying
      birds, a concept supported by genetic similarity with waterfowl isolates from the
      same geographic area and time period. This duck-origin virus had genetic features
      typical of H11 and N9 viruses, including no neuraminidase stalk deletion, no
      differences in putative glycosylation sites in either surface protein, and no
      addition of basic amino acid residues at the hemagglutinin cleavage site compared
      to published sequences. It replicated in both avian and mammalian cells in vitro,
      and experimentally challenged chickens developed mild acute upper respiratory
      lesions but no clinical signs of disease. It elicited immune responses in
      chickens, resulting in seroconversion in all infected birds, although antibody
      titers remained low over the experimental period.

PMID- 18825482
TI  - Cold co-extraction of hemagglutinin and matrix M1 protein from influenza virus A
      by a combination of non-ionic detergents allows for visualization of the raft
      like nature of the virus envelope.
AB  - Membrane solubilization with a mixture of cold non-ionic detergents has been
      applied to isolate detergent-resistant membranes from intact virus A lipid
      bilayer. Association of the viral envelope glycoproteins and M1 into a raft lipid
      protein complex was verified via detergent insolubility experiments, and the
      M1:HA stoichiometry of the proposed supramolecular complex was estimated via
      amino acid analysis. Electron microscopy and dynamic light scattering data
      revealed that these lipid-protein rafts form unilamellar vesicles with HA spikes
      on their surfaces similar to influenza virus virions. Together, our data suggest
      that the cold co-extraction technique visualizes the raft-like nature of the
      viral envelope and demonstrates the interaction of matrix M1 protein with the
      envelope.

PMID- 18825483
TI  - Increased detection of influenza A H16 in the United States.
AB  - As a result of an US interagency avian influenza surveillance effort in wild
      birds, four isolates of influenza A viruses were initially identified as H7 by
      hemagglutination inhibition (HI) but subsequently identified as H16 through
      genetic sequence analysis. We report the development of internal primers for
      amplification and cycle-sequencing of the full-length H16 gene, increased
      detection of H16 within the US, and possible steric inhibition or cross-reaction
      between H7 and H16 antigens during the conventional HI assay. The latter could
      have critical implications for poultry operations if H16 viruses are detected and
      mistakenly reported as H7 viruses.

PMID- 18825484
TI  - Brugmansia suaveolens mottle virus, a novel potyvirus causing leaf mottling of
      Brugmansia suaveolens in Brazil.
AB  - A potyvirus was isolated from Brugmansia suaveolens showing leaf mottling and
      tentatively named Brugmansia suaveolens mottle virus (BsMoV). The virus (isolate
      Bs-Campinas) could infect some solanaceous plants and two Chenopodium species,
      and was transmitted by aphids. Symptomatic leaves contained flexuous particles
      and cylindrical inclusions. RT-PCR amplification using potyvirus universal
      primers produced a DNA fragment of 1851 nt (3' terminal genomic region), which
      shared 71% nucleotide identity with Pepper mottle virus, the best-matched
      potyvirus sequence. Since this identity value is below the threshold currently
      used to discriminate Potyvirus species, Brugmansia suaveolens mottle virus most
      likely represents a new Potyvirus species.

PMID- 18825485
TI  - Effect of two synthetic peptides mimicking conserved regions of equine infectious
      anemia virus proteins gp90 and gp45 upon cytokine mRNA expression.
AB  - Gp90 and gp45 synthetic peptides, which mimic conserved sequences of native viral
      proteins, are recognized by antibodies to equine infectious anemia virus (EIAV)
      in asymptomatic carrier horses and generate humoral and cellular responses in
      immunized mice. Cytokine mRNA levels were evaluated in equine peripheral blood
      mononuclear cells (PBMCs) after in vitro stimulation with gp90 and gp45 with the
      aim of determining the cytokine profile associated with the proliferative
      response. Stimulation index (SI) values indicate that 100 and 60% of EIAV
      infected horses recognized gp90 and gp45, respectively. A strong positive
      correlation was found between IL-12p40 and SI, IFN-gamma and SI, and IL-12p40 and
      IFN-gamma (p < 0.001). These results suggest the presence of specific memory
      cells that would contribute to maintain reinfection resistance and that conserved
      viral regions represented by gp90 and gp45 synthetic peptides may be good
      candidates for inclusion in vaccine strategies against EIAV.

PMID- 18825486
TI  - Neurogenesis and neurite outgrowth in the spinal cord of chicken embryos and in
      primary cultures of spinal neurons following knockdown of Class III beta tubulin
      with antisense morpholinos.
AB  - Microtubules are the primary cytoskeletal constituent of extending neurites. We
      used antisense morpholinos to knock down expression of neuron-specific Class III
      beta tubulin in the right half of the neural tube of chicken embryos in ovo.
      There was a significant (p < 0.01) reduction in the number of Class III beta
      tubulin immunostained interneurons 24 h following electroporation of the
      morpholinos when compared with the contralateral side of the neural tube.
      However, neural crest-derived sensory neurons labeled with the fluorescently
      tagged morpholinos developed distinct processes. Moreover, there was no
      significant difference in the number of interneurons labeled on either side of
      the neural tube with a second marker of developing neurons, anti-microtubule
      associated protein (MAP) 1b. Neural tubes were also excised and dissociated
      following antisense or control morpholino electroporation. The resulting neurons
      were cultured for 48 h and immunostained with anti-Class III beta tubulin and
      anti-MAP 1b. Neurons that had taken up the antisense morpholino had significantly
      shorter neurites (p < 0.01) than neurons from the same neural tubes that did not;
      they also had significantly shorter neurites (p < 0.05) than labeled neurons from
      neural tubes electroporated with a control morpholino. Thus, normal expression of
      Class III beta tubulin may not be necessary for neurogenesis in the early avian
      spinal cord in situ, but is required for neurite outgrowth in vitro.

PMID- 18825487
TI  - Molecular basis of complement factor I (CFI) polymorphism: one of two polymorphic
      suballeles responsible for CFI A is Japanese-specific.
AB  - Isoelectric focusing has revealed that human complement factor I (CFI) is
      controlled by two polymorphic alleles, CFI(*)A and CFI(*)B, and a few rare
      variant alleles. In this study the molecular basis of the CFI polymorphism was
      investigated in 174 Japanese. The CFI(*)A was divided into two suballeles,
      CFI(*)As (R201S) and CFI(*)Ah (R406H). CFI(*)Aj, a rare variant allele
      originating from CFI(*)Ah, had an additional mutation (R502L). The distribution
      of these three mutations and two registered SNPs was investigated in a total of
      2,471 individuals in 20 populations from various areas, and six haplotypes were
      observed. Haplotype H3, which is characterized by CFI(*)As, was found only in Far
      East populations: the frequencies were about 0.03 in the main island of Japan and
      lower than 0.01 in Okinawa and Korea. Haplotype H5, characterized by CFI(*)Ah,
      prevailed almost exclusively in East Asians and was observed at the highest
      frequencies in southern Chinese Han and Thais. CFI(*)Ah must have arisen in a
      southeastern part of Asia and thereafter have spread to neighboring populations.

PMID- 18825488
TI  - Role of cyclooxygenase-2 functional gene polymorphisms in Helicobacter pylori
      induced gastritis and gastric atrophy.
AB  - In India, the role of host genetic factors is poorly studied for Helicobacter
      pylori associated diseases. Therefore, we evaluated the association of
      functionally relevant COX-2 gene polymorphisms (-765 G>C and +8473 T>C) in
      gastritis and precancerous lesions susceptibility. After upper GI endoscopy, 130
      rapid urease test positive patients with non-ulcer dyspepsia, also showed
      positivity for H. pylori using modified Geimsa staining and anti-CagA IgG
      serology were included. All patients and 260 asymptomatic controls were genotyped
      for COX-2 variations using PCR-RFLP. COX-2 -765 (GC+CC) genotypes, -765 C allele,
      +8473 CC genotype, +8473 (TC+CC) genotypes, +8473 C allele, and variant
      haplotypes imparted high risk for gastritis (P = 0.036, OR = 1.82; P = 0.007,
      1.92; P = 0.025, OR = 2.13; P = 0.017, OR = 1.80; P = 0.017, OR = 1.45; P =
      0.010, OR = 2.40; P = 0.023, OR = 1.50 and P = 0.012, OR = 2.20 folds,
      respectively). In contrast, COX-2 -765 C allele carriers had low risk for
      lymphocyte (P = 0.020, OR = 0.35), plasma cell infiltrations (P = 0.016, OR =
      0.33), and gastric atrophy (GA) development (P = 0.019, OR = 0.35). In
      conclusion, COX-2 variant allele/genotype/haplotype carriers may be at high risk
      for gastritis. However, COX-2 -765 C allele carriers may be at low risk for GA
      development.

PMID- 18825489
TI  - Clinical significance of serum HMGB-1 and sRAGE levels in systemic sclerosis:
      association with disease severity.
AB  - INTRODUCTION: The high mobility group box 1 protein (HMGB-1)/advanced glycation
      end products (RAGE) system is recently shown to play an important part in
      immune/inflammatory disorders. However, the association of this system in
      systemic sclerosis (SSc) remains unknown. MATERIALS AND METHODS: To determine
      clinical association of serum levels of HMGB-1 and soluble RAGE (sRAGE) in
      patients with SSc, sera from 70 patients with SSc and 25 healthy controls were
      examined by enzyme-linked immunosorbent assay. Sera from tight-skin mice and
      bleomycin-induced scleroderma mice, animal models for SSc, were also examined.
      Skin HMGB-1 and RAGE expression was assessed by immunohistochemistry. RESULTS AND
      DISCUSSION: Serum HMGB-1 and sRAGE levels in SSc were higher than those in
      controls. Similarly, HMGB-1 and sRAGE levels in animal SSc models were higher
      than those in control mice. SSc patients with elevated HMGB-1 and sRAGE levels
      had more frequent involvement of several organs and immunological abnormalities
      compared to those with normal levels. Furthermore, HMGB-1 and sRAGE levels
      correlated positively with modified Rodnan total skin thickness score and
      negatively with pulmonary function test. CONCLUSIONS: HMGB-1 and sRAGE expression
      in the sclerotic skin was more intense than normal skin. These results suggest
      that elevated serum HMGB-1 and sRAGE levels are associated with the disease
      severity and immunological abnormalities in SSc.

PMID- 18825491
TI  - Oral glyburide, but not glimepiride, blocks the infarct-size limiting effects of
      pioglitazone.
AB  - BACKGROUND: Many patients with type 2 diabetes mellitus receive several oral
      hypoglycemic agents, including sulfonylurea drugs. Intravenous glyburide (Glyb),
      a sulfonylurea agent, blocks the protective effects of "ischemic" and
      pharmacologic preconditioning in various animal models without affecting
      myocardial infarct size when administered alone. However, there are conflicting
      results when other sulfonylurea drugs are used. Pioglitazone (PIO) reduces
      infarct size in the rat. We asked whether oral Glyb and glimepiride (Glim) affect
      the infarct size-limiting effects of PIO. METHODS: Sprague-Dawley rats received 3
      day oral treatment with: PIO (5 mg/kg/day); PIO + Glyb (10 mg/kg/day); PIO + Glim
      (4 mg/kg/day) or water alone (experiment 1) or PIO (5 mg/kg/day) with or without
      5-hydroxydecanoate (5HD, 10 mg/kg), a specific mitochondrial ATP-sensitive K+
      channels inhibitor, administered intravenously 30 min before coronary artery
      ligation. PIO, Glyb and Glim were administered by oral gavage. Sugar 5% was added
      to water to prevent hypoglycemia. Rats underwent 30 min coronary artery occlusion
      and 4 h reperfusion (n = 6 in each group). Ischemic area at risk was assessed by
      blue dye and infarct size by triphenyl-tetrazolium-chloride. RESULTS: Body weight
      and the size of the area at risk were comparable among groups. Infarct size (% of
      the area at risk) was significantly smaller in the PIO (14.3 +/- 1.1%; p < 0.001)
      and PIO + Glim (13.2 +/- 0.8%; p < 0.001) groups than in the control group (37.7
      +/- 1.2%). Glyb completely blocked the effect of PIO (43.0 +/- 1.7%; p < 0.001).
      Glim did not affect the protective effect of PIO (p = 0.993). 5HD blocked the
      protective effect of PIO (infarct size 48.5 +/- 0.8% versus 14.8 +/- 0.6%,
      respectively; p < 0.0001). In conclusion, the infarct size limiting effects of
      PIO are dependent on activation of mitochondrial ATP-sensitive K+ channels. Oral
      Glyb, but not Glim, blocks the infarct size limiting effects of PIO. It is
      plausible that Glyb affects other pleiotropic effects of PIO and thus may
      attenuate favorable effects on cardiovascular outcomes. In contrast, Glim does
      not attenuate the protective effect of PIO.

PMID- 18825492
TI  - Mitochondrial PINK1--a novel cardioprotective kinase?

PMID- 18825493
TI  - Living alone: elderly Chinese Singaporeans.
AB  - Asian societies maintain the norm that older people should live with their
      children. Yet some older people live alone. This is the first study to explore
      social isolation, strategies of coping, and preferences about living arrangements
      among Chinese Singaporeans aged 65+ who live alone. Data from 19 semi-structured
      interviews were analyzed. The elderly people who live alone either have no other
      alternative, or they choose it despite opportunities to live with others.
      Regardless of the initial reason, solo-dwellers in Singapore succeed at living
      alone by developing behavioral and psychological strategies that help overcome
      social isolation. Their main link to the "outside" world is access to medical and
      social services. Despite some hardships, many prefer living alone because it has
      become familiar and personally comfortable.

PMID- 18825494
TI  - An examination of dedifferentiation in cognition among African-American older
      adults.
AB  - The structure and organization of cognitive abilities has been examined across
      the life span. The current analysis had three specific aims: (1) test the factor
      structure of a broad cognitive ability battery across three age groups; (2)
      examine differences in the pattern of factor covariation across age groups; and
      (3) examine the pattern of factor mean differences across age groups. A sample of
      512 older African Americans (mean age = 66.6 years, 25.4% male) from the
      Baltimore Study of Black Aging was administered a battery of cognitive tests
      assessing the domains of perceptual speed, verbal memory, inductive reasoning,
      vocabulary, and working memory. Factor models were estimated separately in middle
      age adults (50-59 years, n = 107), young-old adults (60-69 years, n = 198), and
      old-old adults (70-79 years, n = 207). There was loading invariance across the
      three age groups that suggests that the selected tests measured cognition
      similarly across age. There was no evidence of dedifferentiation across
      increasingly older age groups. Factor mean differences were observed with the
      middle-age group having significantly higher factor means than the young-old and
      old-old groups; however, there was only one factor mean difference between the
      young-old and the old-old groups. The results suggest that a pattern of
      dedifferentiation of cognitive abilities does not exist within this sample of
      older African Americans and that the 60-69 year age range may be a critical
      period for cognitive decline in this population.

PMID- 18825495
TI  - Characterization of H5N1 influenza A viruses isolated from domestic green-winged
      teal.
AB  - Two avian influenza virus strains, A/domestic green-winged teal/Hunan/67/2005
      (H5N1) (D-GWT/67) and A/domestic green-winged teal/Hunan/79/2005 (H5N1) (D
      GWT/79), were isolated from healthy domestic green-winged teals (Anas crecca) in
      Hunan Province, South China. Genomic analysis showed that both isolates were
      reassortants. The hemagglutinin (HA) genes of the two isolates were closely
      related to that of an H5N1 strain isolated from tree sparrow (A/tree
      sparrow/Henan/1/04). The neuraminidase (NA) genes and the internal protein genes
      of both isolates were closely related to those from A/chicken/Shantou/4231/2003
      like (H5N1) viruses, with exception of the matrix (M) gene of D-GWT/79, which was
      closely related to that of the H7N3 strain A/mallard/Netherlands/12/2000 isolated
      from wild mallard duck. The virulence of the two isolates was examined in
      chickens, ducks, and mice. Both strains were found to be highly pathogenic in
      chickens and ducks, but showed low pathogenicity in mice. These findings
      contribute to the realization that domestic green-winged teals carrying the H5N1
      virus may play an important role in transmitting the virus among birds.

PMID- 18825496
TI  - First step in characterization of cis-acting sequences involved in fowl
      adenovirus 1 (CELO) packaging and its effect on the development of a helper
      dependent vector strategy.
AB  - Adenovirus-based vectors are widely developed for potential utilization as
      vectors in vaccine and gene therapy strategies. We focused on developing a helper
      dependent adenoviral (HD-Ad) vector for the potential use of CELO, a member of
      the Aviadenovirus genus, in avian species vaccination. Our aim was to localize
      sequences which could play an essential role in CELO genome encapsidation and,
      when deleted, was unable to produce viruses to develop a helper CELO virus. A
      panel of 6 mutants with deletions between nt 80 and 350 of the CELO genome was
      constructed and characterized for its ability to produce viable virus. To develop
      a helper-dependent adenoviral vector derived from CELO, a helper virus was
      developed by inserting loxP sequences around the region containing the identified
      putative packaging sequences. A LMH (Leghorn Male Hepatocarcinoma) cell line
      expressing Cre recombinase was developed to allow the excision of this region. We
      demonstrated that the region from nt 200 to 250 was important and the region from
      nt 250 to 300 at the left end of the CELO genome was essential for virus
      encapsidation. We also showed that the loxP-flanked region was efficiently
      removed in a Cre expressing cell line to produce a candidate helper virus.

PMID- 18825497
TI  - The cross-generational mother-daughter-aunt-niece design: establishing validity
      of the MDAN design with NLSY fertility variables.
AB  - Using National Longitudinal Survey of Youth (NLSY) fertility variables, we
      introduce and illustrate a new genetically-informative design. First, we develop
      a kinship linking algorithm, using the NLSY79 and the NLSY-Children data to link
      mothers to daughters and aunts to nieces. Then we construct mother-daughter
      correlations to compare to aunt-niece correlations, an MDAN design, within the
      context of the quantitative genetic model. The results of our empirical
      illustration, which uses DF Analysis and generalized estimation equations (GEE)
      to estimate biometrical parameters from NLSY79 sister-sister pairs and their
      children in the NLSY-Children dataset, provide both face validity and concurrent
      validity in support of the efficacy of the design. We describe extensions of the
      MDAN design. Compared to the typical within-generational design used in most
      behavior genetic research, the cross-generational feature of this design has
      certain advantages and interesting features. In particular, we note that the
      equal environment assumption of the traditional biometrical model shifts in the
      context of a cross-generational design. These shifts raise questions and provide
      motivation for future research using the MDAN and other cross-generational
      designs.

PMID- 18825498
TI  - Increasing access to evidence-based smoking cessation treatment: effectiveness of
      a free nicotine patch program among Chinese immigrants.
AB  - Pharmacotherapy substantially increases smoking cessation rates. However,
      programs to reduce barriers to this evidence-based treatment may not improve
      access among high risk immigrant non English speaking populations. This study
      estimates the effectiveness of a tailored free nicotine patch (NRT) program among
      Chinese American smokers living in New York City (NYC). Between July 2004 and May
      2005 NRT was distributed to 375 smokers through two community-based organizations
      that serve the Asian American population in NYC. Participants completed an in
      person baseline survey and a 4-month follow-up telephone survey. Using an
      intention to treat analysis the abstinence rate at 4 months was 26.7% (100/375).
      Predictors of cessation included higher levels of self efficacy at baseline, not
      smoking while using the patch and concern about personal health risks.
      Distribution through easy to access, culturally competent local community
      organizations increased the reach of a free nicotine patch program and assisted
      smokers in quitting.

PMID- 18825499
TI  - Perinatal outcomes among foreign-born and US-born Chinese Americans, 1995-2000.
AB  - This paper examines nativity differences in adverse perinatal outcomes of Chinese
      American mothers. Singleton live births to US-resident Chinese women (150,620
      foreign-born, 15,040 US-born) and a random sample of 150,620 non-Hispanic White
      mothers were selected from 1995 to 2000 national linked birth/infant death
      certificate files. Associations between maternal nativity status and adverse
      perinatal outcomes were assessed using multivariable logistic regressions.
      Compared to US-born Chinese mothers, foreign-born Chinese mothers were less
      likely to be unmarried, teen mothers, have a non-Hispanic White or other race
      partner, be rural residents, and more likely to be less educated, or utilize
      prenatal care inadequately. Controlling for these factors, foreign-born Chinese
      American mothers had significantly lower risks for low birth weight, preterm
      birth, and small-for-gestational age, whereas risks for infant mortality,
      neonatal mortality, and post-neonatal mortality did not differ significantly from
      those of infants of US-born Chinese mothers. Chinese Americans exhibited clear
      nativity differentials for adverse birth outcomes.

PMID- 18825500
TI  - What type of computer-assisted exercise supports young less skilled spellers in
      resolving problems in open and closed syllable words?
AB  - Dutch bisyllabic words containing open and closed syllables are particularly
      difficult to spell for children. What kind of support in spelling exercises
      improves the spelling of these words the most? Two extensions of a commonly used
      dictation exercise were tested: less skilled spellers in grade 2 (n = 50; 7 years
      and 10 months) either received explicit syllabic segmentation cues or received
      spelling cues by means of a visual preview. Comparisons between pre-, post-, and
      retention tests of spelling skill showed that extra syllabic cues did not show a
      significant improvement beyond normal spelling dictation and that visual preview
      was most effective as compared to the other types of training. The findings
      suggest that word-specific knowledge can effectively be improved by exposure to
      the correct letter pattern during exercises in spelling and seems to result in
      lasting improvement of word-specific orthographic representations, at least for 5
      weeks.

PMID- 18825501
TI  - Use of context in the word recognition process by adults with a significant
      history of reading difficulties.
AB  - We examined whether university students who report a significant history of
      reading difficulties (RD; n = 24) differed from university students with no
      history of reading difficulties (NRD; n = 31) in how sentence context affects
      word recognition. Experiment 1 found no differences in how congruent sentence
      primes or syntactic manipulations of the sentence primes affected the performance
      of the two groups. However, only the RD group displayed a significant inhibition
      effect when the target word was preceded by an incongruent sentence prime.
      Experiment 2 found that the groups differed in how meaning frequency of the
      target word and context strength of the sentence prime affected word recognition
      latencies. The results suggest that the RD participants' performance is context
      sensitive and better explained by interactive models of language processing than
      by modular models.

PMID- 18825502
TI  - What, exactly, is cladistics? Re-writing the history of systematics and
      biogeography.
AB  - The development of comparative biology (systematics) has been of interest to
      philosophers and historians. Particular attention has been placed on the 'war' of
      the 1970s and 1980s, the apparent dispute among those who preferred this or that
      methodology. In this contribution we examine the history of comparative biology
      from the perspective of fundamentals rather than methodologies. Our examination
      is framed within the artificial-natural classification dichotomy, a viewpoint
      currently lost from view but worth resurrecting.

PMID- 18825503
TI  - Astyanax bockmanni Vari and Castro, 2007: an ambiguous karyotype in the Astyanax
      genus.
AB  - Despite the widespread distribution of Astyanax bockmanni in streams from Upper
      Parana River system in central, southeastern, and southern Brazil, just recently,
      it has been identified as a distinct Astyanax species. Cytogenetic studies were
      performed in two populations of this species, revealing conservative features. A.
      bockmanni shows 2n = 50 chromosomes, a karyotypic formula composed of 10 M + 12SM
      + 12ST + 16A and multiple Ag-NORs. Eight positive signals in
      subtelocentric/acrocentric chromosomes were identified by fluorescent in situ
      hybridization (FISH) with 18S rDNA probes. After FISH with 5S rDNA probes, four
      sites were detected, comprising the interstitial region of a metacentric pair and
      the terminal region on long arms of another metracentric pair. Little amounts of
      constitutive heterochromatin were observed, mainly distributed at distal region
      in two chromosomal pairs. Additionally, heterochromatin was also located close to
      the centromeres in some chromosomes. No positive signals were detected in the
      chromosomes of A. bockmanni by FISH with the As-51 satellite DNA probe. The
      studied species combines a set of characteristics previously identified in two
      different Astyanax groups. The chromosomal evolution in the genus Astyanax is
      discussed.

PMID- 18825504
TI  - Changes in case mix and treatment patterns in prostate cancer in Saskatchewan
      during the prostate specific antigen testing era.
AB  - BACKGROUND: The prostate specific antigen (PSA) test became available in
      Saskatchewan in 1990 as a part of the provincial health plan. The purpose of this
      population-based study was to describe the changes in case mix and treatment
      patterns for prostate cancer following its introduction. METHODS: The
      Saskatchewan Cancer Registry was used to identify all new cases of prostate
      cancer for the period 1985-2001. We reviewed over 10,000 charts to collect
      information on tumor characteristics, diagnostic methods, and first choice of
      treatment. This information was linked to the demographic and mortality data from
      the registry. RESULTS: The age-adjusted incidence of prostate cancer was
      influenced greatly by PSA testing volumes. Overall, the rate increased from 90.3
      per 100,000 in 1985 to 151.3 per 100,000 in 2001. The increase was mostly organ
      confined moderately differentiated cases. The incidence rate of metastatic
      disease dropped about 50% but only in the 70-79 and 80+ age groups. In 1985, 34%
      of cases were diagnosed by needle biopsy and 60.4% by TURP. In 2001, the values
      were 76.1% and 19.7%, respectively. More men now choose radical therapy as the
      first course of treatment, 81% during 1997-2001 compared to only 63.2% in the
      1985-1989 period. Mortality rates remained stable in all age groups over these
      years. CONCLUSION: There have been dramatic changes in the case mix of prostate
      cancers diagnosed since the introduction of PSA testing in the population and
      significant changes in clinical management of this disease. Thus far, no changes
      have occurred in mortality rates in the population.

PMID- 18825505
TI  - Effect of in vitro exposure to Vibrio vulnificus on hydroelectrolytic transport
      and structural changes of sea bream (Sparus aurata L.) intestine.
AB  - The everted gut sac technique has been used to investigate the effect of Vibrio
      vulnificus on water and electrolyte (Na(+), K(+), Cl(-), HCO(3)(-)) transport on
      the intestine of sea bream (Sparus aurata L.). Both the anterior and the
      posterior intestine were incubated in a medium containing 10(8) V. vulnificus
      cells ml(-1) at 25 degrees C for 2 h. The presence of V. vulnificus resulted in a
      significant reduction (P < 0.05) of water absorption in the anterior intestine,
      while sodium absorption in the anterior (P < 0.01) and posterior (P < 0.05)
      intestine was elevated. Chloride absorption was increased, but the changed was
      not significant, while potassium absorption decreased significantly (P < 0.05),
      but only in the posterior intestine. Incubation the sea bream intestine with V.
      vulnificus did not affect carbonate secretion in the anterior segment, whereas
      high secretion was stimulated in the posterior segment (P < 0.01). Histological
      evaluations demonstrated damage in the anterior intestine of sea bream that was
      characterized by the detachment of degenerative enterocytes, alterations in the
      microvilli, and the presence of a heterogenous cell population, indicating
      inflammation. Based on our results, we conclude that V. vulnificus caused cell
      damage to the intestine of sea bream and that the anterior intestine is more
      susceptible than the posterior part of the intestine. Several hypotheses are
      suggested to explain our observations, such as the presence of higher numbers of
      villosities in the anterior intestine than in the posterior one and/or the
      presence of endogenous bacteria in the posterior intestine which may have a
      protector role.

PMID- 18825506
TI  - Biostructural analysis of the metal-sensor domain of CnrX from Cupriavidus
      metallidurans CH34.
AB  - In Cupriavidus metallidurans CH34, the proteins CnrX, CnrY, and CnrH regulate the
      expression of the cnrCBA operon that codes for a cation-efflux pump involved in
      cobalt and nickel resistance. The periplasmic part of CnrX can be defined as the
      metal sensor in the signal transduction complex composed of the membrane-bound
      anti-sigma factor CnrY and the extra-cytoplasmic function sigma factor CnrH. A
      soluble form of CnrX was overproduced and purified. This protein behaves as a
      dimer in solution as judged from gel filtration, sedimentation velocity
      experiments, and NMR. Native crystals diffracting to 2.3 A using synchrotron
      radiation were obtained using the hanging-drop vapor-diffusion method. They
      belong to the primitive monoclinic space group P2(1), with unit cell parameters a
      = 31.87, b = 74.80, c = 93.67 A, beta = 90.107 degrees. NMR data and secondary
      structure prediction suggest that this protein is essentially formed by helices.

PMID- 18825507
TI  - Patient sources for drug information in Iran: a questionnaire-based survey.
AB  - OBJECTIVES: To identify sources used by patients to obtain drug-related
      information and to find which portion of patients study the Patient Information
      Leaflet (PIL). METHODS: A cluster random sampling was used to select 19 community
      pharmacies in Shiraz, Iran, from 192 pharmacies registered by Food and Drug
      Office of Shiraz University of Medical Sciences. Using a questionnaire, an
      independent assessor surveyed outpatients immediately after their prescriptions
      were dispensed. Results were subjected to statistical analysis. RESULTS: Total of
      671 patients were interviewed, of which 188 patients (28%) reported they received
      no information from pharmacists or physicians and 169 patients (25%) received
      their medications without prescription. Nearly half of the patients (46%) were
      informed on the frequency of use and dose of their medications. Very few patients
      (6%) were appropriately informed about the frequency of use, dosage, duration of
      treatment, and potential side effects, allergies and drug interactions. Patients
      with college education used PILs as a source of information more than those with
      lower education levels. CONCLUSION: A significant portion of patients obtained
      medicines without a prescription. Only a few portion of patients in Shiraz
      received adequate drug information from their physician or pharmacist. A
      considerable portion of patients did not study PILs.

PMID- 18825508
TI  - An oxidized ergosterol from Pleurotus cystidiosus active against anthracnose
      causing Colletotrichum gloeosporioides.
AB  - This study was undertaken to study the antifungal activity of Pleurotus
      cystidiosus against Colletotrichum gloeosporioides. This was achieved by
      fractionating the mushroom, P. cystidiosus initially to acetone (A),
      dichloromethane (D), and hexane (H) and studying the antifungal activity using
      the standard poisoned food technique. All the test solutions used were in the
      concentration of 20,000 ppm. The percentage inhibition of extracts A, D, and H
      was 12, 7, and 0.4%, respectively. Antifungal assay guided fractionation of the
      most active extract A resulted in four fractions; A1, A2, A3, and A4 having 12,
      22, 0, and 17% percentage inhibitions, respectively. Fractions A2 and A4 were
      selected for further purifications. Normal phase column chromatography of A2 gave
      A2-1, A2-2, A2-3, and A2-4, with percentage inhibitions 7, 5, 26, and 13%,
      respectively. The fraction with the highest inhibitory activity (A2-3) was
      further separated using the Chromatotron and a single compound (A2-3-13) with 41%
      inhibition was isolated. Structure elucidation of this compound using 1D and 2D
      NMR spectroscopy proved this compound to be 3beta, 5alpha, 6beta
      trihydroxyergosta-7,22-diene.

PMID- 18825509
TI  - Deriving utility scores from the SF-36 health instrument using Rasch analysis.
AB  - BACKGROUND: Utility scores for use in cost-utility analysis may be imputed from
      the SF-36 health instrument using various techniques, typically regression
      analysis. This paper explored imputation using partial credit Rasch analysis.
      METHOD: Data from the Assessment of Quality of Life (AQoL) instrument validation
      study were re-analysed (n = 996 inpatients, outpatients and a community sample).
      For each AQoL item, factor analysis identified those SF-36 items forming a
      unidimensional scale. Rasch analysis located scale logit scores for these SF-36
      items. The logit scores were used to assign AQoL item scores. The standard AQoL
      scoring algorithm was then applied to obtain the utility scores. RESULTS: Many SF
      36 items were limited predictors of AQoL items; some items from both instruments
      obtained disordered thresholds. All imputed scores were consistent with the AQoL
      model and fell within AQoL score boundaries. The explained variance between
      imputed and true AQoL scores was 61%. DISCUSSION: Rasch-imputed mapping, unlike
      many regression-based algorithms, produced results consistent with the axioms of
      utility measurement, while the proportion of explained variance was similar to
      regression-based modelling. Item properties on both instruments implied that some
      items should be revised using Rasch analysis. The methods and results may be used
      by researchers needing to impute utility scores from SF-36 health scores.

PMID- 18825511
TI  - Abstracts of the Neurocritical Care Society 6th Annual Meeting. October 23-25,
      2008. Miami, Florida, USA.

PMID- 18825510
TI  - Avoiding empty rhetoric: engaging publics in debates about nanotechnologies.
AB  - Despite the amount of public investment in nanotechnology ventures in the
      developed world, research shows that there is little public awareness about
      nanotechnology, and public knowledge is very limited. This is concerning given
      that nanotechnology has been heralded as 'revolutionising' the way we live. In
      this paper, we articulate why public engagement in debates about nanotechnology
      is important, drawing on literature on public engagement and science policy
      debate and deliberation about public policy development. We also explore the
      significance of timing in engaging the public, and we make some suggestions
      concerning how to effectively engage publics. Our conclusions indicate the
      significance of scientific researchers, policy makers and representative consumer
      groupings in public reasoning towards a better public policy framework for debate
      about technological development.

PMID- 18825512
TI  - Initiation of therapy with a subcutaneously administered antiretroviral in
      treatment-experienced HIV-infected patients: understanding physician and patient
      perspectives.
AB  - Enfuvirtide (Fuzeon) is the first self-injectable antiretroviral (ARV) therapy
      approved for the treatment of HIV. This study was undertaken to explore the
      perceptions of injectable ARVs among physicians and treatment-experienced HIV
      infected patients and identify potential motivators or barriers to the initiation
      of injectable ARV therapies. This empirical study was conducted based on
      qualitative field research conducted in multiple centres in five European
      countries and the US. A purposive sampling strategy was employed and structured
      interviews carried out with physicians and patients. Discussion guides for these
      interviews focused on attitudinal responses to a range of key areas. For
      physicians, these areas included HIV treatment, treatment-experienced patients
      and their relationships with them and injectable therapy usage, while for
      patients - some of whom were receiving enfuvirtide therapy - the focus included
      relationships with their physicians and attitudes towards injectable ARV therapy.
      Sixty-eight physicians and 43 patients were interviewed. Qualitative analysis of
      the interview responses revealed a number of recurring themes among physician and
      patient perceptions of HIV and its treatment. Physicians tended to view
      injectable ARVs as a last resort, with only limited suitability among treatment
      experienced patients and a low level of patient acceptability. In contrast,
      patients generally perceived the potential value of effective injectable ARV
      therapy, if recommended to them by their physicians, indicating that its benefits
      could outweigh the drawbacks associated with its administration. This study
      identified some potential disconnects between physician and patient perceptions
      of injectable therapy. Our findings emphasize the need for patients to discuss
      their treatment goals with their physicians so that they can work together to
      find the regimen that is most likely to achieve these goals.

PMID- 18825513
TI  - A model for community representation and participation in HIV prevention trials
      among women who engage in transactional sex in Africa.
AB  - Actively engaging communities in effective partnerships for the design and
      implementation of HIV prevention research is vital to the successful conduct of
      ethically robust, locally-appropriate clinical trials in developing countries.
      This is especially true in vulnerable at-risk sub-populations, where definitions
      of "community", "participation" and "representation" can be difficult to apply.
      This study was conducted to investigate the feasibility of a participatory model
      of community liaison among an occupational cohort of women at high-risk of HIV
      and sexually-transmitted infections in Mwanza City, northwest Tanzania in
      preparation for a Phase III vaginal microbicide trial. This approach was rooted
      in participatory action-orientated research and used tools adapted from
      participatory learning and action techniques. During the feasibility study, a
      mobile community-based sexual and reproductive health service for women working
      as informal food vendors or in traditional and modern bars, restaurants, hotels
      and guesthouses was established in 10 city wards. Participatory mapping was
      carried out by project fieldworkers and wards divided into 78 geographical
      clusters of facilities in consultation with community members and study
      participants. Representatives at cluster and ward level were elected in a process
      facilitated by the site Community Liaison Officer and a site-level Community
      Advisory Committee established. A logical framework was used to guide the
      implementation, monitoring and evaluation of the community liaison system (CLS)
      within the broader feasibility study. The CLS was essential to the successful
      conduct of the feasibility study and has now been consolidated and expanded as
      part of the on-going MDP301 Phase III microbicide trial in Mwanza. The
      participatory model presented in this paper is likely to be generalisable to
      other vulnerable, stigmatised, at-risk study populations in resource-limited
      settings.

PMID- 18825514
TI  - Understanding the variation in costs among HIV primary care providers.
AB  - The paper uses a hybrid cost model to identify the determinants of cost variation
      among programs that offer early intervention services to people living with HIV
      and AIDS in the US. The model combines the effects of input price and output
      volume measures from traditional economic cost functions with institutional
      factors based on program and patient characteristics on the cost of providing
      primary medical care and support services to people living with HIV and AIDS. The
      impact of economic factors conforms to conventional theory and reveals the
      potential for cost savings through greater economies of scale and
      substitutability of low cost for high cost labor inputs. Similarly, programs that
      use staff more efficiently and share an affiliation with other organizations
      exhibit lower costs than more labor intensive and non-affiliated providers.
      However, patient characteristics are equally important determinants of program
      spending. Minority patients use services less frequently and generate fewer
      costs, while patients facing fewer barriers to care, such as those with Medicaid
      coverage, access services more frequently and incur higher costs. Uninsured
      patients also generate higher costs, but the higher costs associated with this
      subgroup more likely stem from a lack of continuity in care and, thus, poorer
      health status and greater healthcare needs when treatment is sought. Injection
      drug users require less expensive services, but access services more frequently
      than other risk groups, while patients with an AIDS diagnosis and those who are
      co-infected with hepatitis C require more program resources. By separately
      estimating the economic and institutional determinants of program costs, the
      study highlights the relative importance of factors that are amendable to
      internal cost control efforts versus those that reflect the resource needs of
      local communities.

PMID- 18825515
TI  - Quality indicators for depression care in HIV patients.
AB  - HIV patients are at increased risk for depression. However, a comprehensive set
      of quality of care indicators for depression in the context of HIV does not
      exist. We report the results of a recent expert panel convened to develop a
      comprehensive set of HIV depression quality indicators. We systematically
      reviewed the depression and HIV depression literature to provide the evidence for
      the quality indicators. The HIV depression quality indicators were divided into
      six chapters: general, bereavement, substance abuse, viral hepatitis, cognitive
      impairment and drug interactions. A modified Delphi expert panel method was used
      to evaluate the validity and feasibility of the candidate quality indicators. The
      expert panel included HIV physicians, psychiatrists and a pharmacist, all with
      experience with HIV depression. The in-person eleven-member panel rated 80
      candidate HIV-depression quality indicators. Indicators were evaluated using main
      and sensitivity analysis criteria for validity and feasibility. Seventy-four
      percent (59/80) of the quality indicators met a priori main analysis criteria for
      validity and feasibility and 61% met sensitivity analysis criteria. Approved
      indicators that are more specific to HIV depression include: depression screening
      frequency; depression screening and treatment in the context of hepatitis C;
      optimizing depression and HIV treatment in the context of cognitive impairment;
      and starting antidepressants at lower doses but advancing to doses typical for
      the general population. Most adverse medication interaction indicators did not
      meet main analysis validity criteria. The quality indicators identified in this
      study provide a useful tool for measuring and informing the quality of HIV
      depression care.

PMID- 18825516
TI  - Comparison of knowledge and accessibility to information sources of HIV/AIDS
      between blind and sighted populations in Nigeria.
AB  - The aim of this study was to compare the HIV/AIDS knowledge and accessibility to
      HIV/AIDS information between blind and sighted individuals in Nigeria. A cross
      sectional survey was undertaken among rural and urban blind (57) and sighted (62)
      adolescents in 2006. A structured questionnaire was used to collect data about
      HIV/AIDS symptoms, transmission and prevention knowledge, as well as
      accessibility to sources of HIV/AIDS information. Binary logistic regression and
      chi-square statistics were applied to compare responses between the two
      populations. Blindness was found to be associated with diminished knowledge of
      HIV/AIDS transmission, prevention and symptoms. At the same time, the blind rely
      on different sources of HIV/AIDS information than sighted respondents. A lack of
      knowledge and limited accessibility to proper sources of information causes the
      blind disabled to be more vulnerable. It is necessary to supply them with proper
      information and increase their HIV/AIDS knowledge.

PMID- 18825517
TI  - Qualitative to quantitative: linked trajectory of method triangulation in a study
      on HIV/AIDS in Goa, India.
AB  - With 3.1 million people estimated to be living with HIV/AIDS in India and 39.5
      million people globally, the epidemic has posed academics the challenge of
      identifying behaviours and their underlying beliefs in the effort to reduce the
      risk of HIV transmission. The Health Belief Model (HBM) is frequently used to
      identify risk behaviours and adherence behaviour in the field of HIV/AIDS. Risk
      behaviour studies that apply HBM have been largely quantitative and use of
      qualitative methodology is rare. The marriage of qualitative and quantitative
      methods has never been easy. The challenge is in triangulating the methods.
      Method triangulation has been largely used to combine insights from the
      qualitative and quantitative methods but not to link both the methods. In this
      paper we suggest a linked trajectory of method triangulation (LTMT). The linked
      trajectory aims to first gather individual level information through in-depth
      interviews and then to present the information as vignettes in focus group
      discussions. We thus validate information obtained from in-depth interviews and
      gather emic concepts that arise from the interaction. We thus capture both the
      interpretation and the interaction angles of the qualitative method. Further,
      using the qualitative information gained, a survey is designed. In doing so, the
      survey questions are grounded and contextualized. We employed this linked
      trajectory of method triangulation in a study on the risk assessment of HIV/AIDS
      among migrant and mobile men. Fieldwork was carried out in Goa, India. Data come
      from two waves of studies, first an explorative qualitative study (2003), second
      a larger study (2004-2005), including in-depth interviews (25), focus group
      discussions (21) and a survey (n=1259). By employing the qualitative to
      quantitative LTMT we can not only contextualize the existing concepts of the HBM,
      but also validate new concepts and identify new risk groups.

PMID- 18825518
TI  - Uptake of an HIV voluntary counseling and testing program for pregnant women in
      Georgia.
AB  - From 2002 to 2005 the Elizabeth Glaser Pediatric AIDS Foundation prevention of
      mother-to-child transmission of HIV project operated in Georgia and was managed
      by the Maternal and Child Care Union. The project covered Tbilisi, the capital,
      and included 34 clinics that provide women's healthcare. Out of 35,385 pregnant
      women starting prenatal care in clinics involved in the project, 91% (32,262) had
      received HIV counseling and, among those counseled, 94% (30,330) were tested for
      HIV antibodies; 14 pregnant women (<0.001%) were found to be HIV-infected.

PMID- 18825519
TI  - Differences between Internet and community samples of MSM: implications for
      behavioral surveillance among MSM in China.
AB  - This study compared the difference between two samples of men who have sex with
      men (MSM) in Harbin, China, using cross-sectional data that were collected via
      the Internet and through conventional venue-based outreach. All participants in
      both samples lived in or nearby Harbin in northeast China. Results showed that
      the Internet sample was significantly younger, more educated and more likely to
      be students and to self-identify as homosexual than the community sample. After
      controlling for demographic characteristics, the community sample was more likely
      to have had sex with females (OR 2.01, CI 1.22-3.30, p=0.006) and to have had >
      or =6 male partners in the previous six months than the Internet sample (OR 4.88,
      CI 3.51-6.80, p<0.001). No significant difference was observed in the prevalence
      of unprotected anal intercourse, exchanging sex for money, exchanging money for
      sex or illicit drug use between the two samples. For those seeking sex both on
      the Internet and in traditional gay venues, participants in the community sample
      were nearly three times more likely to have had > or =6 male partners during the
      previous six months than those in the Internet sample (p=0.001). In conclusion,
      the online and offline samples of MSM are significantly different and carry
      different levels of risk for HIV transmission. Using the Internet as a data
      collection method may serve as an additional mechanism for the existing gay venue
      based behavioral surveillance system in China.

PMID- 18825520
TI  - To tell or not to tell: South African women's disclosure of HIV status during
      pregnancy.
AB  - HIV-positive pregnant women often do not disclose their serostatus to their
      partners, family and friends, creating potential barriers to preventing sexual
      transmission to partners and mother-to-child transmission through breastfeeding.
      This research explores recently diagnosed HIV-positive pregnant women's reasons
      for disclosure and non-disclosure of serostatus to various members of their
      social networks, as well as the consequences of their disclosure. Data were
      collected through open-ended questions as part of a semi-structured interview
      with 293 recently diagnosed HIV-positive pregnant women recruited from antenatal
      clinics in two townships in Tshwane, South Africa. A content analysis of
      responses showed that women weighed fear of abandonment and discrimination
      against their desire to raise risk awareness and their need for support. Partners
      most often responded to disclosure with disbelief and shock, whereas parents
      frequently exhibited emotional distress, but were still supportive, as were other
      relatives and friends. The women subsequently experienced low levels of adverse
      consequences after disclosure. The results can assist healthcare providers in
      understanding the complexity of pregnant women's decisions to disclose to various
      members of their social networks and emphasize the need for continued counselling
      and support.

PMID- 18825521
TI  - Behavioral prevention study gauges HIV/AIDS and depression in the older US
      population.
AB  - According to the National Institute of Health (NIH, 1997) the number of older
      Americans with HIV or AIDS is growing. Cumulative estimated number of HIV/AIDS
      cases in the US for ages 50-54 was 56,950. Furthermore, the number of newly
      infected persons 65 years and older has grown considerably in the last ten years.
      Several reports indicate that the attitudes and knowledge of older Americans
      appears be less responsive compared to other age cohorts (CDC, 2003, 2007). This
      may be attributed to the lack of prevention programs geared towards older persons
      and physician comfort levels with geriatric patients in discussing sexuality.
      While it is important to attribute this longevity to the emergence of highly
      active antiretroviral therapy, consideration must also be made for the mental
      well-being of this cohort, as evidenced by the effectiveness of antiretroviral
      chemotherapy and the prevalence of depressive disorders unique to older
      populations. The unique co-morbidity of clinical depression and HIV/AIDS presents
      unique challenges to the physician and other healthcare providers. The NIH
      awarded $1.6 million to the University of Ohio Health Psychology Program in 2006
      to examine how older Americans are coping with HIV/AIDS.

PMID- 18825522
TI  - Time perception in children with ADHD: the effects of task modality and duration.
AB  - The purpose of the current study was to examine the performance of children with
      and without ADHD in time reproduction tasks involving varying durations and
      modalities. Twenty children with ADHD and 20 healthy controls completed time
      reproduction tasks in three modalities (auditory, visual, and a unique combined
      auditory/visual condition) and six durations (1 second, 4 seconds, 12 seconds, 24
      seconds, 48 seconds, and 60 seconds). Consistent with our predictions, we found
      main effects of group (participants with ADHD were significantly less accurate
      than those without ADHD), duration (accuracy decreased as temporal duration
      increased), and modality (responses in the combined condition were more accurate
      than those in the auditory condition, which in turn were more accurate than those
      in the visual condition). Furthermore, predicted interactions between group and
      duration (the discrepancy in performance between the two groups grew as temporal
      duration increased), and group and modality (the modality effect was of greater
      for participants with ADHD) were supported. A marginal, nonsignificant
      interaction between group, modality, and duration was also found. These findings
      are discussed in relation to current theory on the nature of cognitive deficits
      evident in individuals with ADHD, and methodological limitations are noted.

PMID- 18825523
TI  - Differential development of learning strategies on a Pictorial Verbal Learning
      Test (PVLT) in primary-school children.
AB  - The aim of this study was to test the hypothesis that developmental differences
      exist in the use of learning strategies in primary school children. Serial and
      subjective clustering in a multitrial Pictorial Verbal Learning Test (PVLT) were
      compared in 79 children aged 6-12. Correlation analyses indicated that serial
      clustering yielded better performance when information was presented on the
      initial trials of the test. Subjective clustering was superior when information
      was presented repeatedly, i.e., after three or more trials. Analyses of variance
      indicated that subjective clustering was used more often in older children with
      repeated presentations. On the other hand, there was no increase in the use of
      serial clustering with age and with repeated presentations. The findings imply
      that training in the use of proper strategies could have benefit for children who
      use an inefficient learning strategy and/or have a learning problem. In addition,
      they point to the importance of the factor "age" in relation to the way
      information is presented to children.

PMID- 18825524
TI  - Executive functioning in children with Fetal Alcohol Spectrum Disorders: profiles
      and age-related differences.
AB  - The goal of this project was to examine the profile of executive function (EF)
      deficits and age-related differences among children with FASD. Twenty-nine
      children with FASD (8 to 16 years of age) completed 8 tests from the Delis-Kaplan
      Executive Function System (D-KEFS). They had difficulty on many components of EF
      including cognitive flexibility, inhibition, some measures of verbal fluency,
      abstract thinking, deductive reasoning, hypothesis testing, problem solving, and
      concept formation. A distinctive profile emerged with performance being poorest
      on the card sorting test and relatively high on category fluency, design fluency,
      and the tower test, indicating relative strengths on some visual-spatial EF
      tasks. Older children with FASD showed more difficulty (relative to the norm) on
      some verbal tests of EF than younger children with FASD, suggesting that
      difficulty on some verbal EF tasks appears to become more pronounced with
      increasing age.

PMID- 18825525
TI  - The use of liquid self-microemulsifying drug delivery systems based on peanut
      oil/tween 80 in the delivery of griseofulvin.
AB  - Peanut oil and Tween 80 blends devoid of any cosurfactant were employed in the
      formulation of different batches of liquid self-microemulsifying drug delivery
      systems (LSMEDDS) and their suitability as vehicles for the delivery of a typical
      lipophilic drug-griseofulvin-was investigated. The LSMEDDS were evaluated using
      the following parameters: phase separation, globule size, viscosity, solubility
      of griseofulvin, and partition coefficient. The release profile of griseofulvin
      from the optimized LSMEDDS was evaluated in citrate/phosphate buffer solutions of
      pH 2.0, pH 6.5, and pH 7.4. The results obtained indicated that there was
      significantly higher (alpha </= 0.05) percentage cumulative amounts of
      griseofulvin released from the LSMEDDS in comparison with that released from
      peanut oil alone. The release of griseofulvin from the LSMEDDS into aqueous media
      of pH 6.5 and pH 7.4 showed enhanced and controlled dissolution of the drug from
      the formulation. Incorporation of griseofulvin into this proposed formulation is
      suggested as a strategy to overcome the irregular dissolution and absorption
      behaviors often associated with conventional griseofulvin tablets.

PMID- 18825526
TI  - Synthesis of a novel linear polymer of a macrocyclic polyamine copper (II)
      complex and its interaction with plasmid DNA.
AB  - The novel linear polymer of a macrocyclic polyamine copper (II) complex, which
      has many cyclen groups linked by epichlorohydrin, has been synthesized as a DNA
      cleavage agent. The structure of the polymer 3 was identified by 1HNMR and IR and
      its molecular weight was measured by GPC. The result of agarose gel
      electrophoresis assay showed that Cu-(II) complex 4 could act as a powerful
      catalyst for the cleavage of plasmid DNA under physiological conditions.

PMID- 18825527
TI  - Acetylcholinesterase/butyrylcholinesterase inhibition activity of some new
      carbacylamidophosphate derivatives.
AB  - Eight newly synthesized carbacylamidophosphates with the general formula
      RC(O)NHP(O)Cl2 with R = pCl-C6H4 1a, pBr-C6H4 2a, C6H5 3a, and pMe-C6H4 4a and
      RC(O)NHP(O)(NC4H8O)2 R = pCl-C6H4 1b, pBr-C6H4 2b, C6H5 3b, pMe-C6H4 4b, were
      selected to compare the inhibition kinetic parameters, IC50, Ki, kp and KD, on
      human erythrocyte acetylcholinesterase (hAChE) and bovine serum
      butyrylcholinesterase (BuChE), Also, the in vivo inhibition potency of compound
      2a, 2b and 3a, were studied. The data demonstrates that compound 2a and compound
      2b are the potent sensitive as AChE and BuChE inhibitors respectively, and the
      inhibition of hAChE is about 10-fold greater than that of BuChE.

PMID- 18825528
TI  - In vitro reactivation of trichlorfon-inhibited butyrylcholinesterase using HI-6,
      obidoxime, pralidoxime and K048.
AB  - Trichlorfon is a specific inhibitor of cholinesterases. It was typically used as
      an insecticide; however, trichlorfon was described as useful for symptomatic
      treatment of Alzheimer's disease some years ago. The presented study is aimed at
      reactivation of trichlorfon-inhibited butyrylcholinesterase since this enzyme
      play an important role in Alzheimer's disease as deputy for acetylcholinesterase
      and furthermore it could be applied as a scavenger in case of overdosing. We used
      in vitro reactivation test for considering only reactivation efficacy of
      butyrylcholinesterase that is inhibited by trichlorfon and not reactivation of
      butyrylcholinesterase inhibited by trichlorfon metabolic products. Four
      reactivators were used: HI-6, pralidoxime, obidoxime, and K048. Although all of
      the reactivators seem to be effective at 1 mM concentration, a lower
      concentration was not able ensure sufficient reactivation. There was also an
      observed lowering of reactivation efficacy when butyrylcholinesterase was exposed
      to trichlorfon for a longer time interval.

PMID- 18825530
TI  - Synthesis and biological activities of new hydrazide derivatives.
AB  - The synthesis of a new series of imidazo[1,2-a]pyrazine-2-carboxylic acid
      arylidene-hydrazides is described. The chemical structures of the compounds were
      elucidated by IR, (1)H-NMR, FAB(+)-MS spectral data. Their biological activity
      against various bacteria, fungi species, and Mycobacterium tuberculosis was
      investigated. Antibacterial activity was measured against Escherichia coli (NRRL
      B-3704), Staphylococcus aureus (NRRL B-767), Salmonella typhimurium (NRRL B
      4420), Proteus vulgaris (NRLL B-123), Enterococcus faecalis (isolated obtained
      from Faculty of Medicine Osmangazi University, Eskisehir, Turkey), Pseudomonas
      aeruginosa (NRRL B-23 27853), Klebsiella spp. (isolated obtained from Faculty of
      Medicine Osmangazi University, Eskisehir, Turkey), while antifungal activity was
      evaluated against Candida albicans (isolates obtained from Osmangazi Uni. Fac.of
      Medicine), Candida glabrata (isolates obtained from Osmangazi Uni. Fac.of
      Medicine). Compounds were also evaluated for antituberculosis activity against
      Mycobacterium tuberculosis H(37)Rv using the BACTEC 460 radiometric system and
      BACTEC 12B medium. The compounds showed moderate inhibitor effects against human
      pathogenic microorganisms., whereas the preliminary results indicated that all of
      the tested compounds were inactive against Mycobacterium tuberculosis H(37)Rv.

PMID- 18825531
TI  - Calpain inhibitory flavonoids isolated from Orostachys japonicus.
AB  - The n-butanol (n-BuOH) fraction of Orostachys japonicus A. Berger (Crassulaceae)
      significantly inhibited calpain activity. Through the activity-guided isolation
      from the n-BuOH fraction, herbacetin 8-O-alpha-D-ribopyranoside (1), kaempferol
      (2), quercetin (3), afzelin (4), astragalin (5), isoquercetin (6) and quercitrin
      (7) were obtained. Their structures were determined by spectroscopic techniques.
      Among them, compound 3 and 5 had significant calpain inhibitory activities.

PMID- 18825532
TI  - Antibacterial, antifungal, insecticidal, cytotoxicity and phytotoxicity studies
      on Indigofera gerardiana.
AB  - The antibacterial, antifungal, acute cytotoxicity, phytotoxicity and insecticidal
      profile of the crude extract and various fractions of Indigofera gerardiana have
      been studied. Six bacterial and fungal strains were used, of which Samonella
      typhi and Microsporum canis were the most susceptible strains with MICs 0.37
      mg/mL and 0.09 mg/mL, respectively. The crude extract and the fractions showed
      low insecticidal activity against Sitophilus oryzae, Rhyzopertha dominica and
      Callosbruchus analis but no activity against Tribolium castaneum. The brine
      shrimp lethality assay showed absence of any measurable cytotoxicity of the crude
      extract and fractions, showing a good safety profile at a preliminary level. All
      the fractions except crude extract revealed profound and highly significant
      herbicidal activity against Lemna minor at the concentration of 1000 microg/mL.
      Indigofera gerardiana was shown by in-vitro assays to be a potential source for
      natural antifungal, antibacterial and herbicidal agents.

PMID- 18825533
TI  - Anti-inflammatory, analgesic and antipyretic activities of Physalis minima Linn.
AB  - In our present investigation, the crude methanol extract and chloroform fraction
      of the whole plant of Physalis minima Linn (Solanaceae) was investigated for anti
      inflammatory, analgesic and antipyretic activities in NMRI mice and Wistar rats
      of either sex at 200 and 400 mg/kg, respectively. Various established in-vivo
      model's were used during the study. Both crude extract and chloroform fraction
      showed marked anti-inflammatory and analgesic activities as compared to a control
      at tested doses. The antipyretic potential of the crude extract and chloroform
      were insignificant in the Brewer's yeast fever model. Therefore, the whole plant
      of Physalis minima Linn could be considered as a potential candidate for
      bioactivity-guided isolation of natural anti-inflammatory and analgesic agents.

PMID- 18825534
TI  - Cubebin and derivatives as inhibitors of mitochondrial complex I. Proposed
      interaction with subunit B8.
AB  - The effects on mitochondrial respiration and complex I NADH oxidase activity of
      cubebin and derivatives were evaluated. The compounds inhibited the state 3
      glutamate/malate-supported respiration of hamster liver mitochondria with IC(50)
      values ranging from 12.16 to 83.96 microM. NADH oxidase reaction was evaluated in
      submitochondrial particles. The compounds also inhibited this activity, showing
      the same order of potency observed for effects on state 3 respiration, as well as
      a tendency towards a non-competitive type of inhibition (K(I) values ranging from
      0.62 to 16.1 microM). A potential binding mode of these compounds with complex I
      subunit B8, assessed by docking calculations, is proposed.

PMID- 18825535
TI  - Aromatic esters of progesterone as 5alpha-reductase and prostate growth
      inhibitors.
AB  - The aim of this study was to determine the biological activity of 4 steroidal
      derivatives (9a, 9b and 10a, 10b) prepared from the commercially available
      17alpha acetoxyprogesterone, where 9a, 9b, have the Delta(4)-3-oxo structure and
      10a and 10b an epoxy group at C-4 and C-5. These steroids were tested as
      inhibitors of 5alpha-reductase enzyme, which is present in androgen-dependent
      tissues and converts testosterone to its more active reduced metabolite
      dihydrotestosterone. The pharmacological effect of these steroids was
      demonstrated by the significant decrease of the weight of the prostate gland of
      gonadectomized hamsters treated with testosterone plus finasteride or with
      steroids 10a and 10b. For the studies in vitro the IC(50) values were determined
      by measuring the steroid concentration that inhibits 50% of the activity of
      5alpha-reductase. In this study we also determined the capacity of these steroids
      to bind to the androgen receptor present in the rat prostate cytosol. The results
      from this work indicated that compounds 9a, 9b, 10a, and 10b inhibited the 5alpha
      reductase activity with IC(50) values of 360, 370, 13 and 4.9 nM respectively.
      However these steroids did not bind to the androgen receptors since none competed
      with labeled mibolerone. Steroid 10b, an epoxy steroidal derivative containing
      bromine atom in the ester moiety, was the most active inhibitor of 5alpha
      reductase enzyme, present in human prostate homogenates with an IC(50) value of
      4.9 nM and also showed in vivo pharmacological activity since it decreased the
      weight of the prostate from hamsters treated with testosterone in a similar way
      as finasteride.

PMID- 18825536
TI  - Chemical constituents isolated from Polygala japonica leaves and their inhibitory
      effect on nitric oxide production in vitro.
AB  - A methanolic extract of dried leaves of Polygala japonica Houtt (Polygalaceae)
      significantly attenuated nitric oxide production in lipopolysaccharide-simulated
      BV2 microglia. Five anthraquinones chrysophanol (1), emodin (2), aloe-emodin (3),
      emodin 8-O-beta-D-glucopyranoside (4) and trihydroxy anthraquinone (5), and four
      flavonoids kaempferol (6), chrysoeriol (7), kaempferol 3-gentiobioside (8) and
      isorhamnetin (9) were isolated from the methanolic extract using bioactivity
      guided fractionation. Among them, compounds 1-4, 6 and 7 showed significant
      inhibitory effect on lipopolysaccharide-induced nitric oxide production in BV2
      microglia at the concentrations ranging from 1.0 to 100.0 microM.

PMID- 18825537
TI  - Green tea catechins in chemoprevention of cancer: a molecular docking
      investigation into their interaction with glutathione S-transferase (GST P1-1).
AB  - The anti- and pro-oxidant effects of green tea catechins have been implicated in
      the alterations of cellular functions determining their chemoprotective and
      therapeutic potentials in toxicity and diseases. The glutathione S-transferases
      (GSTs; EC 2.5.1.18) family is a widely distributed phase-II detoxifying enzymes
      and the GST P1-1 isoenzyme has been shown to catalyze the conjugation of GSH with
      some alkylating anti-cancer agents, suggesting that over-expression of GST P1-1
      would result in tumor cell resistance. Here we report the docking study of four
      green tea catechins and four alkylating anticancer drugs into the GST P1-1 model,
      as GSTs were found to be affected by tea catechins. The EGCG ligands exhibit
      higher docking potential with respect to the anticancer agents, with a ligand
      receptor interaction pattern indicating an high conformational stability.
      Consequently, the competition mechanisms favourable for the green tea catechins
      could lead to enzyme(s) desensitisation with a reduction of the alkylating drugs
      metabolism. The results provide a useful theoretical contribution in
      understanding the biochemical mechanisms implicated in the chemotherapeutic use
      of green tea catechins in oxidative stress-related diseases.

PMID- 18825538
TI  - Effectiveness of commercial inhibitors against subtype F HIV-1 protease.
AB  - Subtype F wild type HIV protease has been kinetically characterized using six
      commercial inhibitors (amprenavir, indinavir, lopinavir, nelfinavir, ritonavir
      and saquinavir) commonly used for HIV/AIDS treatment, as well as inhibitor TL-3
      and acetyl-pepstatin. We also obtained kinetic parameters for two multi-resistant
      proteases (one of subtype B and one of subtype F) harboring primary and secondary
      mutations selected by intensive treatment with ritonavir/nelfinavir. This newly
      obtained biochemical data shows that all six studied commercially available
      protease inhibitors are significantly less effective against subtype F HIV
      proteases than against HIV proteases of subtype B, as judged by increased K(i)
      and biochemical fitness (vitality) values. Comparison with previously reported
      kinetic values for subtype A and C HIV proteases show that subtype F wild type
      proteases are significantly less susceptible to inhibition. These results
      demonstrate that the accumulation of natural polymorphisms in subtype F proteases
      yields catalytically more active enzymes with a large degree of cross-resistance,
      which thus results in strong virus viability.

PMID- 18825540
TI  - Maximal oxygen uptake versus maximal power output in children.
AB  - Maximal oxygen uptake VO(2max)) is considered the optimal method to assess
      aerobic fitness. The measurement of VO(2max), however, requires special equipment
      and training. Maximal exercise testing with determination of maximal power output
      offers a more simple approach. This study explores the relationship between
      [Vdot]O(2max) and maximal power output in 247 children (139 boys and 108 girls)
      aged 7.9-11.1 years. Maximal oxygen uptake was measured by indirect calorimetry
      during a maximal ergometer exercise test with an initial workload of 30 W and 15
      W x min(-1) increments. Maximal power output was also measured. A sample (n =
      124) was used to calculate reference equations, which were then validated using
      another sample (n = 123). The linear reference equation for both sexes combined
      was: VO(2max) (ml x min(-1)) = 96 + 10.6 x maximal power + 3.5 . body mass. Using
      this reference equation, estimated VO(2max) per unit of body mass (ml x min(-1) x
      kg(-1)) calculated from maximal power correlated closely with the direct
      measurement of VO(2max) (r = 0.91, P <0.001). Bland-Altman analysis gave a mean
      limits of agreement of 0.2+/-2.9 (ml x min(-1) x kg(-1)) (1 s). Our results
      suggest that maximal power output serves as a good surrogate measurement for
      VO(2max) in population studies of children aged 8-11 years.

PMID- 18825541
TI  - Towards a unified understanding of relative age effects.
AB  - When athletes are placed into annual age groups to organize and coordinate sport
      participation, certain (dis)advantages occur as a result of the subtle age
      differences within these groups. These differences, termed "relative age
      effects", have been consistently related to youth and adult sport attainment.
      However, there has been a lack of consistency in the terminology used in this
      area of research. In this paper, we consider the operational terms used in
      relative age research, discuss appropriate applications of terminology, and
      suggest directions for future research. Importantly, we argue for a unified
      understanding of what "relative age" means, stressing the need for clarity in
      directing future advances in the field.

PMID- 18825543
TI  - Estimation of drug solubility in polymers via differential scanning calorimetry
      and utilization of the fox equation.
AB  - The solubility of drugs in polyethylene glycol 400 (PEG 400) was estimated and
      rank ordered using a differential scanning calorimetry (DSC) method and the Fox
      Equation. Drug-polymer binary mixtures of six compounds (Ibuprofen, Indomethacin,
      Naproxen, and three proprietary compounds: PC-1 through PC-3) with PEG 400 were
      heat treated using a three-cycle DSC method to establish a correlation between
      equilibrium solubility and temperature. Thermal events such as heat of fusion,
      heat of recrystallization and glass transition temperature, T(g), were used to
      calculate the drug solubility at multiple higher temperatures through the Fox
      Equation. Subsequently, a van't Hoff plot was constructed to estimate the drug
      solubility at room temperature, and the values were compared with those measured
      by HPLC. With the exception of Naproxen, room temperature solubilities of the
      remaining drug compounds in PEG 400 were determined by this thermal method
      approach, and compared with those measured by HPLC: 26.7% vs. 24.7% for
      Ibuprofen, 5.8% vs. 9.6% for Indomethacin, 3.1 % vs. 1.5% for PC-1, 2.3% vs. 1.3%
      for PC-2, and 1.4% vs. 0.2% for PC-3 in PEG 400. There was good concordance in
      solubility rank order estimates between the two methods. These collective results
      support the potential utility of the thermal method as an alternative to other
      methods for estimation of drug solubility in polymers which is an important
      determinant in the design of physically-stable amorphous systems.

PMID- 18825544
TI  - Instructiveness of feedback during clerkships: influence of supervisor,
      observation and student initiative.
AB  - BACKGROUND: Several authors assume that the supervisor's role, observation of
      behaviour and students' active participation are important factors in the
      instructiveness of feedback. AIM: This study aims to provide empirical evidence
      for these expectations. METHODS: For two weeks, 142 clerks from eight hospitals
      recorded for each individual feedback event: who provided the feedback, whether
      the feedback was based on observation of behaviour, who initiated the feedback
      moment and the perceived instructiveness of the feedback. Data were analysed with
      multilevel techniques. RESULTS: The perceived instructiveness of feedback
      provided by specialists and residents did not differ significantly. However, both
      were perceived to be more instructive than feedback from nursing and paramedical
      staff (beta(specialists) = 0.862, p < 0.01; beta(residents) = 0.853, p < 0.01).
      Feedback on behaviour that had been directly observed was reported to be more
      instructive than feedback on behaviour that had not been observed (beta(observed)
      = 0.314, p < 0.001). Feedback which stemmed from student initiative or a joint
      initiative was experienced to be more instructive than feedback which ensued from
      the supervisor's initiative (beta(student) = 0.441, p < 0.01; beta(joint) =
      0.392, p < 0.01). CONCLUSIONS: The expectations concerning the influence of
      observation and student initiative on the instructiveness of feedback were
      confirmed in this empirical study. Expected differences in instructiveness
      between feedback from specialists and residents were not confirmed.

PMID- 18825545
TI  - Preparing medical students to become skilled at clinical observation.
AB  - BACKGROUND: Observation is a fundamental skill for physicians and it is has been
      the subject of a resurgent interest. Although strategies for teaching observation
      have been described previously, many of them linked conceptually to emerging
      insights in visual literacy and aesthetic development, principles of clinical
      observation have not been elucidated. AIMS: The purpose of this study was to
      develop a set of principles that would be useful in guiding educators teach
      medical students how to observe. METHODS: The authors conducted a comprehensive
      review of the literature on the history and theory of clinical observation. They
      then consulted a group of individuals from a highly diverse background who, based
      on the nature of their work, were considered to have expertise in observation.
      RESULTS: Informed by the literature and the group of experts, the authors
      developed a set of four guiding principles relating to pedagogy and eight core
      principles of clinical observation. In the context of curriculum renewal at the
      Faculty of Medicine, McGill University, these principles were then used to create
      specific teaching modules. CONCLUSIONS: Principles that are pragmatic in nature,
      anchored in a theoretical framework of visual competence and applicable to
      medical education have been developed and successfully deployed.

PMID- 18825546
TI  - Transdermal iontophoresis of hydromorphone across hairless rat skin in vitro.
AB  - The feasibility of delivering hydromorphone by transdermal iontophoresis to
      obtain therapeutically effective analgesic concentrations for the management of
      cancer-related pain was evaluated. Anodal iontophoresis was performed, and the
      effect of current strength, current duration, solution pH, presence of buffer
      ions, and drug concentration on the transdermal permeation of hydromorphone was
      investigated in vitro. Freshly excised full-thickness hairless rat skin and side
      by-side permeation cells connected to the Phoresor II with Ag/AgCl electrodes was
      used. The flux of hydromorphone was observed to significantly increase (P < 0.05)
      from 72.04-280.30 microg/cm(2)/h with increase in current strength from 0.10-0.50
      mA. A linear relationship was obtained between hydromorphone flux and current
      strength. Furthermore, the flux of hydromorphone was influenced by solution pH
      and presence of buffer ions. Also, the in vitro permeation flux of hydromorphone
      was observed to significantly increase (P < 0.05) with a 10-fold increase in
      hydromorphone hydrochloride concentration from 0.01-0.10 M. However, with further
      increase to 0.50 M, there was no significant difference in flux. These results
      show that by manipulating electronic and formulation variables, the transdermal
      iontophoretic delivery of hydromorphone can be controlled, and therapeutically
      effective concentrations of hydromorphone for the management of cancer-related
      pain can be obtained.

PMID- 18825547
TI  - Internal carotid artery fibromuscular dysplasia in arterial hypertension:
      management in clinical practice.
AB  - Fibromuscular dysplasia (FMD) reminds of a rare form of secondary arterial
      hypertension occurring in young people and involving the renal arteries. FMD may
      also involve vertebral, subclavian, mesenteric, iliac arteries and carotid
      arteries. FMD of internal carotid arteries is a rare finding that is frequently
      incidental and asymptomatic. It usually occurs in middle-aged women and is
      secondary to media-intima fibrodysplasia. The carotid artery may be elongated or
      kinked and associated cerebral aneurysms have been reported. Symptoms including
      transient ischaemic attack or stroke are uncommon and are related to decrease of
      blood flow or embolization by platelet aggregates. At the onset, differential
      diagnosis with vasculitis must be placed. Computed tomography or magnetic
      resonance imaging (MRI) angiography demonstrates bilateral high-grade stenosis
      with the characteristic "string of beads" pattern. Antiplatelet medication is the
      accepted therapy for asymptomatic lesions. Graduated endoluminal surgical
      dilation is an outmoded therapy, no longer used in most medical centres. Current
      percutaneous angioplasty is the preferred treatment for symptomatic carotid FMD,
      but no randomized controlled trials comparing this methodology with surgery is
      available. The management of a case of arterial systemic FMD in a 52-year-old
      women, diagnosed after a hypertensive crysis, is discussed. Imaging methods
      disclosed stenoses of carotid arteries, of celiac tripod and of superior
      mesenteric artery. Because of high risk associated to endovascular surgery,
      medical therapy was started. In the first year of follow-up, no events have been
      reported.

PMID- 18825548
TI  - Adolescent methamphetamine use and sexual risk behaviour in secondary school
      students in Cape Town, South Africa.
AB  - This study investigated involvement in substance use and sexual activities among
      adolescents in Cape Town, and specifically the associations between
      methamphetamine use and sexual risk behaviours. Data were collected from 15
      randomly selected and 15 matched schools in Cape Town via quantitative
      questionnaires. Students used hand-held computers (PDAs) to answer the questions.
      A total of 4605 grade 9 students were sampled. Male and female students were
      almost equally likely to have used methamphetamine at least once (13% versus
      12%). Students who had used methamphetamine in the past 30 days were
      significantly more likely to have had vaginal, anal or oral sex than students who
      had never used it, to have been pregnant/been responsible for a pregnancy and to
      have been diagnosed with a sexually transmitted infection. Logistic regression
      analysis indicated significant associations between methamphetamine use in the
      past 12 months and engaging in vaginal and anal sex. Drug abuse and sexually
      transmitted infections (STI) prevention services should incorporate the link
      between drugs and STI into their prevention and education strategies, especially
      those aimed at school-going adolescents.

PMID- 18825549
TI  - Injecting risk behaviour and related harm among men who use performance- and
      image-enhancing drugs.
AB  - INTRODUCTION AND AIMS: Performance- and image-enhancing drugs have the potential
      to be a significant public health issue. Detailed data on PIEDs injection are
      difficult to obtain because of the illicit and unsupervised way in which many
      PIEDs are used, and the hidden nature of the group. Our study examines the
      patterns of use, risk behaviours and related harm associated with PIEDs
      injection. We also report the ways in which PIEDs users currently seek injecting
      equipment and harm-reduction advice. DESIGN AND METHOD: Data were obtained via a
      structured questionnaire administered in face-to-face interviews with 60 men who
      used PIEDs (primarily anabolic androgenic steroids) for non-medical purposes.
      RESULTS: Although the rates of needle sharing were low (5%), the men more
      frequently reported re-use of needles/equipment, injecting from a shared
      container (bladders, vials, etc.), injecting other illicit drugs, injecting
      insulin and targeting small muscle groups. Self-reports of being hepatitis C
      antibody positive were associated with lifetime use of heroin and injection of
      other illicit drugs. All HIV positive participants were gay/bisexual men.
      Participants reported a range of other injection-related injuries and diseases
      such as fevers, scarring and abscesses. 'Risky' injectors (38% of participants)
      were more likely to initiate PIEDs use at a younger age, use PIEDs in a larger
      number of cycles per year and report involvement in a violent/aggressive incident
      than 'low risk' injectors and report involvement in a violent/aggressive incident
      than 'low risk' injectors. Participants mainly reported seeking information about
      PIEDs from internet sites (62%) and friends (55%). CONCLUSIONS: An over-reliance
      on personal networks and internet forums limits this groups' access to objective
      harm reduction advice and primary care services. Targeted, PIEDs-specific
      interventions are needed.

PMID- 18825550
TI  - Antioxidant and neuroprotective effects of synthesized sintenin derivatives.
AB  - Three series of sintenin derivatives (compounds 1-14) were designed and prepared
      and their antioxidative and neuroprotective effects were evaluated. The in vitro
      models of scavenging 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals, chelating
      ferrous ions, inhibiting the rat brain homogenates lipid peroxidation, and
      protecting neurons damaged by hydrogen peroxide were employed for bioassays. It
      was found that sintenin derivatives 4 and 13 showed remarkable antioxidative and
      neuroprotective activities.

PMID- 18825551
TI  - Synthesis and preliminary screening of novel N-{2-[4-(substituted)piperazin-1-yl]
      2-oxoethyl}acetamides as potential atypical antipsychotic agents.
AB  - A series of N-{2-[4-(substituted)piperazin-1-yl]-2-oxoethyl}acetamides were
      synthesized as prospective novel atypical antipsychotic agents. Microwave
      irradiation of acetyl glycine (I) with substituted piperazines in the presence of
      DCC in DMF for about 3-5 min gave the titled compounds (P:1-7). All the
      synthesized compounds were screened for their in vivo pharmacological activity in
      Swiss albino mice. D(2) antagonism studies were performed using the climbing
      mouse assay model and 5-HT(2A) antagonism studies were performed using quipazine
      induced head twitches in mice. Among the synthesized compounds P4 was found to be
      the most active compound.

PMID- 18825552
TI  - Modeling of cyclooxygenase-2 and 5-lipooxygenase inhibitory activity of apoptosis
      inducing agents potentially useful in prostate cancer chemotherapy: derivatives
      of diarylpyrazole.
AB  - The structure-activity models of the twenty derivatives for COX-2 and ten
      derivatives of 1,5-diarylpyrazole for 5-LOX inhibitory activity have been
      investigated using Combinatorial Protocol in Multiple Linear Regression (CP-MLR)
      with topological descriptors which were calculated from DRAGON software. Among
      the descriptor classes considered collectively in the study the COX-2 inhibitory
      activity was, however, correlated with topological (TOPO) and Galvez topological
      charge indices (GVZ). Modified Burden eigenvalues (BCUT) and 2D autocorrelations
      (2DAUTO) classes of descriptors have shown correlation to 5-LOX inhibitory
      activity. The developed models and participating descriptors in them have
      suggested that the substitutional modification in the diarylpyrazole moiety may
      have sufficient scope in optimization of prevailing inhibitory activities of
      these analogues.

PMID- 18825553
TI  - Protein glycation inhibitory activities of Lawsonia inermis and its active
      principles.
AB  - The protein glycation inhibitory activity of ethanolic extract of Lawsonia
      inermis (henna) plant tissues was evaluated in vitro using the model system of
      bovine serum albumin and glucose. Protein oxidation and glycation are
      posttranslational modifications that are implicated in the pathological
      development of many age-related disease processes. This study investigated the
      effects of Lawsonia inermis ethanolic extract and its components, on protein
      damage induced by a free radical generator in in vitro assay system. We found
      that alcoholic extract of Lawsonia inermis can effectively protect against
      protein damage and showed that its action is mainly due to Lawsone. In addition,
      the presence of gallic acid also plays an important role in the protective
      activity against protein oxidation and glycation. Two known compounds, namely,
      Lawsone and gallic acid previously isolated from this plant were subjected to
      glycation bioassay for the first time. It was found that the alcoholic extract,
      lawsone (1) and gallic acid (2) showed significant inhibition of Advanced
      Glycated End Products (AGEs) formation and exhibit 77.95%, 79.10% and 66.98%
      inhibition at a concentration of 1500 microg/mL, 1000 microg/mL and 1000 microM
      respectively. Lawsonia inermis, compounds 1 and 2 were found to be glycation
      inhibitors with IC(50) 82.06 +/- 0.13 microg/mL, 67.42 +/- 1.46 microM and 401.7
      +/- 6. 23 microM respectively. This is the first report on the glycation activity
      of these compounds and alcoholic extract of Lawsonia inermis.

PMID- 18825554
TI  - Macrocyclic inhibitors for the serine protease plasmin.
AB  - Macrocyclic inhibitors for the serine protease plasmin were synthesized and
      evaluated. The inhibitors were constructed starting from a cyclohexanone core.
      This core was linked to either the C- or N-terminus of a peptide so that the
      inhibitors were designed to interact with the non-primed or primed binding sites
      of the protease. Macrocycles were prepared by connecting the side chain of Tyr or
      Trp, via a short linker, to one end of the peptide. The activities of the
      macrocyclic inhibitors, while modest, were up to 10-fold more potent than a
      related non-cyclic analog.

PMID- 18825555
TI  - In vitro effects of peroxynitrite treatment on fish liver catalase activity.
AB  - The effect of peroxynitrite (PN), a highly toxic agent, on catalase (CAT)
      activity in fish liver microsomal homogenates was determined. PN was synthesized
      by mixing acidic hydrogen peroxide solution with sodium nitrite solution and then
      adding sodium hydroxide solution into the mixture in order to stabilize the
      highly labile compound peroxynitrous acid (ONOOH) in peroxynitrite anion form
      (ONOO(- )). The effect of PN and decomposed peroxynitrite (DPN), prepared by
      preincubation with HCl, was monitored by using a constant amount of homogenate
      containing the CAT enzyme. Significant losses were observed in the CAT activity
      of fish liver enzyme after treatment with PN and also with DPN products, the
      inhibitory effect of PN being slightly more pronounced than that of DPN. IC(50)
      values were 5.5 and 8.5 microM for PN and DPN, respectively. The PN inhibition of
      CAT activity is due to both the effects of the secondary and decomposition
      products of PN and its nitration and oxidation effects on the amino acid residues
      of the enzyme.

PMID- 18825556
TI  - Design, synthesis, characterization and in vitro antimicrobial evaluation of 4,6
      diaryl-4,5-dihydro-2-phenyl-2H-indazol-3-ols.
AB  - New 4,6-diaryl-4,5-dihydro-2-phenyl-2H-indazol-3-ols 25-32 were designed,
      synthesized and in vitro microbially evaluated using clinically isolated
      bacterial strains viz Staphylococcus aureus, beta-Heamolytic streptococcus,
      Vibreo cholerae, Salmonella typhii, Shigella felxneri and fungal strains viz
      Aspergillus flavus, Mucor, Rhizopus and Microsporum gypsuem. Results of this
      study showed that the nature of the substituents on the phenyl rings viz.,
      methyl, methoxy, chloro, nitro as well as the bromo functions at the meta and
      para positions of the aryl moieties determined the nature and extent of the
      activity of the fused indazolonol compounds 25-32.

PMID- 18825557
TI  - Metal based isatin-derived sulfonamides: their synthesis, characterization,
      coordination behavior and biological activity.
AB  - Some isatin derived sulfonamides and their transition metal [Co(II), Cu(II),
      Ni(II), Zn(II)] complexes have been synthesized and characterized. The structure
      of synthesized compounds and their nature of bonding have been inferred on the
      basis of their physical (magnetic susceptibility and conductivity measurements),
      analytical (elemental analyses) and spectral (IR, (1)H NMR and (13)C NMR)
      properties. An octahedral geometry has been suggested for Co(II), Ni(II) and
      Zn(II) and square-planar for Cu(II) complexes. In order to assess the
      antibacterial and antifungal behavior, the ligands and their metal(II) complexes
      were screened for their in vitro antibacterial activity against four Gram
      negative species, Escherichia coli, Shigella flexneri, Pseudomonas aeruginosa and
      Salmonella typhi and two Gram-positive species, Staphylococcus aureus and
      Bacillus subtilis and, for in vitro antifungal activity against Trichophyton
      longifusus, Candida albicans, Aspergillus flavus, Microsporum canis, Fusarium
      solani and Candida glaberata. In vitro cytotoxic properties of all the compounds
      were also studied against Artemia salina by brine shrimp bioassay. The results of
      average antibacterial/antifungal activity showed that zinc(II) complexes were
      found to be the most active against one or more bacterial/fungal strains as
      compared to the other metal complexes.

PMID- 18825558
TI  - Effect of vibration training on neuromuscular output with ballistic knee
      extensions.
AB  - The aim of the study was to determine whether vibration applied directly to a
      muscle-tendon could enhance neuromuscular output during and 1.5 and 10 min after
      a bout of ballistic resistance training. Fourteen participants were exposed to
      two training conditions in random order: exercise with vibration and exercise
      with sham vibration. The exercise comprised three sets of ballistic knee
      extensions with a load of 60-70% of one-repetition maximum. Vibration (1.2 mm
      amplitude, 65 Hz frequency) was applied with a portable vibrator strapped over
      the distal tendon of the quadriceps. Knee joint angular velocity, moment, and
      power, and rectus femoris and vastus lateralis electromyography root-mean-squared
      were measured during knee extension. During and after training, the vibration did
      not induce significant changes in peak angular velocity, time to peak angular
      velocity, peak moment, time to peak moment, peak power, time to peak power, or
      average EMG of the rectus femoris and vastus lateralis. We conclude that direct
      vibration, at the selected amplitude and frequency, does not enhance these
      neuromuscular variables in ballistic knee extensions during or immediately after
      training.

PMID- 18825559
TI  - Impact of the transition from a conventional to an integrated contextual medical 
      curriculum on students' learning patterns: a longitudinal study.
AB  - BACKGROUND: Until now, most research studying the impact of curriculum
      innovations on student learning patterns was restricted to short term or cross
      sectional research. AIM: Studying longitudinal changes in student learning
      patterns parallel to the implementation of a curriculum innovation from a
      discipline based to an integrated contextual medical curriculum (ICMC). METHODS:
      A post hoc study applying General Linear Model ANOVA one-way repeated-measures.
      The inventory of learning styles(126-item version) is used to determine changes
      in student learning patterns. RESULTS: Though not all hypotheses could be
      accepted, the results suggest a significant impact of the ICMC on learning
      processing strategies; regulation strategies; and on learning orientations. The
      clear build-up of the curriculum and vertical and horizontal integration of
      subject knowledge seem to have significantly reduced lack of regulation and
      promoted at an earlier stage structuring, relating, critical processing and
      vocational-orientation. The effect on use of sources of knowledge, self
      regulation of learning content and certificate-orientation was less important
      than expected. It was yet not possible to confirm the hypothesis that ICMC
      students become better in translating study topics into their own phrasing or
      expressions; and neither the expected impact on vocation-orientation could be
      confirmed. CONCLUSIONS: There is little doubt that the present results are
      important to curriculum (re)designers and those interested in the evaluation of
      curriculum reforms.

PMID- 18825560
TI  - Computer based assessments--mind your eyes!

PMID- 18825561
TI  - Medical students' attitudes to complementary and alternative medicine: further
      validation of the IMAQ and findings from an international longitudinal study.
AB  - BACKGROUND: Current research mainly employs cross-sectional designs to examine
      changes in medical students' attitudes towards complementary and alternative
      medicine (CAM). AIMS: This paper reports the findings of a longitudinal study to
      further validate the Integrative Medicine Attitude Questionnaire (IMAQ) and
      examine changes in medical students' attitudes over 3 years. METHODS: A total of
      154 medical students from four schools in three countries completed a modified
      version of the IMAQ during their first (T1) and fourth year (T2). RESULTS: We
      established the validity of a three-factor model for the IMAQ: (1) attitudes
      towards holism; (2) attitudes towards the effectiveness of CAM therapies, and (3)
      attitudes towards introspection and the doctor-patient relationship. We found
      that IMAQ factor scores did not differ significantly from T1 to T2, emphasizing
      the relative stability in attitudes across time. Various student characteristics
      were significantly associated with IMAQ factor scores at T2: age, gender, CAM
      use, CAM education and school; and two variables (gender and CAM use) predicted
      changes in medical students' attitudes between T1 and T2. CONCLUSIONS: We urge
      medical educators to continue exploring medical students' attitude changes
      towards CAM and we provide examples of what further research is needed.

PMID- 18825562
TI  - Is there a place for medical students in research laboratories? A student's
      perspective.
AB  - Based on personal experience gained in two medical schools, one from a developed
      and one from a developing European country, I present a short discourse on the
      introduction of undergraduate medical students to research. The potential benefit
      of research for professional profile and overall competency building is
      emphasized and the possibility of counterbalancing the present crisis in academic
      medicine through undergraduate research is discussed.

PMID- 18825563
TI  - Assessment in the Foundation Programme: a qualitative study of consultants and
      junior doctors in the South West of England.

PMID- 18825564
TI  - Twelve tips for the use of mobile technologies for work based assessment.
AB  - There is increasing interest in the use of mobile technologies (including
      personal digital assistants (PDAs) and mobile phones) for work based assessment.
      These devices can offer data collection anytime and any place but they can also
      enhance the assessment process by collecting a variety of multimedia. The
      experience of using mobile technologies for work based assessment in a range of
      professions has highlighted several important aspects that need to be considered.
      It is essential that the choice of technology is determined by the overall
      assessment strategy. Important technology aspects include the choice of device
      and the method of data collection and transfer. An initial pilot scheme is
      recommended before widespread adoption so that institutional cultural and
      information technology (IT) barriers can be identified and overcome.

PMID- 18825565
TI  - Reflective learning and the Net Generation.
AB  - Net Generation undergraduate medical students often have low engagement with
      reflective learning because it does not match their learning preferences. In our
      survey of all first-year students, the main learning preferences were bodily
      kinaesthetic and interpersonal. Those students with the highest scores in their
      written reflective learning assessment generally had linguistic and interpersonal
      learning preferences. We suggest that all educators consider how reflective
      learning is implemented in the curriculum and recommend further research to
      determine if our findings are generalizable.

PMID- 18825566
TI  - Leadership curriculum in undergraduate medical education: a study of student and
      faculty perspectives.
AB  - BACKGROUND: Leaders in medicine have called for transformative changes in
      healthcare to address systems challenges and improve the health of the public.
      The purpose of this study was to elicit the perspectives of students, faculty
      physicians and administrators regarding the knowledge and competencies necessary
      in an undergraduate leadership curriculum. METHODS: A mixed-methods study was
      conducted using focus group discussions and semi-structured interviews with
      faculty physicians and administrative leaders, as well as a written survey of
      medical student leaders. RESULTS: Twenty-two faculties participated in focus
      groups and interviews; 21 medical students responded to the written survey.
      Participants identified emotional intelligence, confidence, humility and
      creativity as necessary qualities of leaders; and teamwork, communication,
      management and quality improvement as necessary knowledge and skills. Students
      perceived themselves as somewhat or fully competent in communication (90%),
      conflict resolution (70%) and time management (65%), but reported minimal or no
      knowledge or competence in coding and billing (100%), writing proposals (90%),
      managed care (85%) and investment principles (85%). Both faculty and students
      believed that experiential training was the most effective for teaching
      leadership skills. CONCLUSIONS: Study participants identified the necessary
      qualities, knowledge and skills to serve as goals for an undergraduate leadership
      curriculum. Future studies should address optimal methods of teaching and
      assessing leadership skills among medical students.

PMID- 18825567
TI  - The development of self-efficacy beliefs during general practice vocational
      training: an exploratory study.
AB  - INTRODUCTION: Retention of general practitioners (GPs) is crucial to ensure
      appropriate primary care. However, some recently qualified GPs feel unprepared
      for practice, which may lead them to leave the profession or restrict their scope
      of practice. The development of self-efficacy beliefs during vocational training
      may be an important factor in this phenomenon. METHODS: Five focus groups with a
      total of 28 GP trainees and recent graduates were conducted in Belgium and
      France. Initial analysis using the immersion-crystallisation method was followed
      by analysis using Bandura's self-efficacy framework. RESULTS: Participants
      described beginning their training with low self-efficacy beliefs. Most
      participants described how they overcame stressful situations. Some, however,
      seemed to be developing avoidance strategies. Successfully resolving patient
      problems, sharing experiences with peers and receiving positive feedback from
      supervisors, colleagues and patients were conducive to the development of
      positive self-efficacy beliefs. DISCUSSION: Although low self-efficacy beliefs
      are natural at the beginning of training, participants seemed to develop in two
      ways, either overcoming their fears or avoiding them. Identifying the pattern of
      trainees' responses to allow tailoring of interventions should be investigated by
      those who run training programs. Interventions could include reassurance, peer
      interaction and an appropriate degree of autonomy.

PMID- 18825568
TI  - Quality assurance of item writing: during the introduction of multiple choice
      questions in medicine for high stakes examinations.
AB  - BACKGROUND: One Norwegian medical school introduced A-type MCQs (best one of
      five) to replace more traditional assessment formats (e.g. essays) in an
      undergraduate medical curriculum. Quality assurance criteria were introduced to
      measure the success of the intervention. METHOD: Data collection from the first
      four year-end examinations included item analysis, frequency of item writing
      flaws (IWF) and proportion of items testing at a higher cognitive level (K2). All
      examinations were reviewed before after delivery and no items were removed.
      RESULTS: Overall pass rates were similar to previous cohorts examined with
      traditional assessment formats. Across 389 items, the proportion of items with
      >or=5% of candidates marking two or more functioning distracters was >or=47.5%.
      Removal of items with high p-values (>or=85%), this item distracter proportion
      became >75%. With each successive year in the curriculum the proportion of K2
      items used rose steadily to almost 50%. 31/389 (7%) items had IWFs. 65% items had
      a discriminatory power, >or=0.15. CONCLUSIONS: Five item quality criteria are
      recommended: (1) adherence to an in-house style, (2) item proportion testing at
      K2 level, (3) functioning distracter proportion, (4) overall discrimination ratio
      and (5) IWF frequency.

PMID- 18825569
TI  - A randomized controlled trial comparing instructions regarding unsafe response
      options in a MCQ examination.
AB  - BACKGROUND: Marking of multiple choice type examinations often just takes account
      of the correct responses. This may encourage guessing of incorrect and
      potentially unsafe responses. Ideally responses should contain a high proportion
      of correct, unsafe and the use of 'don't know' response rather than incorrect.
      AIM: This study explored the effect of instructions on responses. METHODS: Fourth
      and fifth-year students sitting for an optional multiple choice examination were
      randomized to receive one of four instruction options: number-correct marking
      (the control group); alert to unsafe; mark deduction for unsafe; or correction
      for guessing. RESULTS: A total of 210 students sat the test. For the fourth-year
      cohort, compared with the control group, being alerted to unsafe and mark
      deduction for unsafe or incorrect responses were associated with graduated
      increases in the use of 'don't know' and reductions in incorrect responses. For
      the fifth-year cohort, there were no differences in responses between options.
      The fifth-year cohort, gave more correct, and fewer incorrect, unsafe and 'don't
      know' responses. CONCLUSIONS: Both the year group and instructions had an effect.
      Being alerted to potentially unsafe responses, even when there is no mark
      deduction penalty, had an effect, although mark deduction still had the greatest
      effect. Assessment instructions may give subliminal messages that have important
      consequences.

PMID- 18825570
TI  - Attributes of effective community preceptors for pre-clerkship medical students.
AB  - BACKGROUND: Attributes of effective precepting of pre-clerkship medical students
      in community settings are not adequately described. As part of preceptor needs
      assessment, we conducted site visits over three consecutive years. We also
      measured the preceptorships' educational quality, using students' post-rotation
      data, to identify priority areas for faculty development, corroborate site visit
      findings, and assess functions of the site visit. METHODS: Three university
      faculty directly observed teaching encounters in 83 community preceptors' offices
      during a 12-18-week second year (pre-clerkship) medical student rotation. Data
      were collected on practice demographics, teaching content, and educational
      quality, using multiple measures. Narrative responses to interview questions were
      coded for prevalent themes. Student post-rotation assessments were obtained by
      anonymous online evaluations. RESULTS: Good precepting attributes and suggestions
      for improvement were identified from both narrative analysis and student post
      rotation evaluations in these key areas: independence in patient assessment, time
      spent teaching, giving feedback and orientation to the preceptor's practice.
      Student evaluations of preceptors' effectiveness significantly improved from year
      1 to 2 and persisted into year 3. Appropriate faculty development strategies were
      derived from the combined results. CONCLUSIONS: The site visit by university
      faculty allows real-time observation and may itself be an effective intervention
      for improving teaching and learning.

PMID- 18825571
TI  - Implementing arthritis clinical practice guidelines in primary care.
AB  - BACKGROUND: Multi-faceted interventions are among the strongest methods for
      changing provider behavior. AIMS: This paper reports the design, implementation
      and process evaluation of an educational program to disseminate clinical practice
      guidelines (CPGs) on the management of rheumatoid arthritis (RA) and
      osteoarthritis (OA) in primary care. METHODS: Organizations were invited to
      participate in inter-professional workshops on OA and RA followed by six months
      of activities to support the delivery of care in the community. Confidence in
      ability to manage arthritis was assessed at baseline using a 10 point numerical
      rating scale. Qualitative assessments were done immediately and 3-12 months post
      workshop. RESULTS: 646 multidisciplinary providers from 216 organizations
      attended one of 30 workshops. Providers (n = 584) reported moderate confidence in
      managing arthritis: family physicians: mean: SD = 7.46(1.42), n = 145; nurse
      practitioners: 6.10(1.84), n = 73; other health care professionals: 5.23(2.83), n
      = 389. Participants identified team learning, the opportunity to network and the
      involvement of trained patient educators as strong features of the workshops. At
      follow-up, participants indicated the greatest impact of the program was on
      collaborative care (83%) and patient self-management (79%). CONCLUSIONS:
      Qualitative results suggest that inter-professional learning may be a successful
      strategy for improving the delivery of collaborative arthritis care and
      supporting patient self-management.

PMID- 18825572
TI  - Assessing teamwork in medical education and practice: relating behavioural
      teamwork ratings and clinical performance.
AB  - BACKGROUND: Problems with communication and team coordination are frequently
      linked to adverse events in medicine. However, there is little experimental
      evidence to support a relationship between observer ratings of teamwork skills
      and objective measures of clinical performance. AIM: Our main objective was to
      test the hypothesis that observer ratings of team skill will correlate with
      objective measures of clinical performance. METHODS: Nine teams of medical
      students were videotaped performing two types of teamwork tasks: (1) low fidelity
      classroom-based patient assessment and (2) high fidelity simulated emergent care.
      Observers used a behaviourally anchored rating scale to rate each individual on
      skills representative of assertiveness, decision-making, situation assessment,
      leadership, and communication. A checklist-based measure was used to assess
      clinical team performance. RESULTS: Moderate to high inter-observer correlations
      and moderate correlations between cases established the validity of a
      behaviourally anchored team skill rating tool for simulated emergent care. There
      was moderate to high correlation between observer ratings of team skill and
      checklist-based measures of team performance for the simulated emergent care
      cases (r = 0.65, p = 0.06 and r = 0.97, p < 0.0001). CONCLUSIONS: These results
      provide prospective evidence of a positive relationship between observer ratings
      of team skills and clinical team performance in a simulated dynamic health care
      task.

PMID- 18825573
TI  - Psychological factors in retrograde amnesia: self-deception and a broken heart.
AB  - We explored potential contributing psychological factors in a patient ('XF') with
      focal retrograde amnesia, within the framework proposed by Kopelman (2000,
      Cognitive Neuropsychology, 17, 585). In particular, we investigated the
      psychological trait of self-enhancement. We constructed a self-report
      questionnaire measure of self-enhancement and compared XF's score on this measure
      with the scores of 61 control participants. XF was found to have a significantly
      greater level of self-enhancement than the entire control group, and also than a
      smaller sample of age- and sex-matched controls. We propose that heightened self
      enhancement may reflect a premorbid tendency that potentially predisposes
      individuals to develop retrograde amnesia.

PMID- 18825574
TI  - Moving beyond Disability: ISPO 12th World Congress, July 2007, Vancouver, Canada.

PMID- 18825575
TI  - The modern era of orthotics.
AB  - The past 40 years has seen the field of orthotics change from a craft-based
      industry into a modern clinical specialty. The author describes his personal view
      of some of the most important developments during this period in the areas of
      manufacturing and materials, patient/orthosis matching, biomechanics, joint
      design and standards. Some likely areas of future development are suggested.

PMID- 18825576
TI  - Using the common sense self-regulation model to determine psychological
      predictors of prosthetic use and activity limitations in lower limb amputees.
AB  - PURPOSE: There are around 800 lower limb amputations performed each year in
      Scotland, however one unpublished study showed that 20% of fitted transtibial
      amputees do not use, and 20% only occasionally use, their prosthesis at one-year
      follow-up. This finding has implications for patients' well-being and healthcare
      cost efficiency. Leventhal's common sense self-regulation model (CS-SRM), a
      social cognition model in health psychology, was used to determine if
      psychological variables would predict prosthetic use and activity limitations in
      lower limb amputees. METHOD: A longitudinal study recruited 166 peripheral
      arterial disease amputees (aged: 50+ yrs). The illness perception questionnaire
      revised (IPQ-R) assessed psychological variables at 3-4 weeks post-operatively.
      Items from the functional measure for amputees (FMA) assessed prosthetic use and
      the locomotor capabilities index (LCI) evaluated activity limitations at 1-month
      and 6-months post-discharge. Outcome variables were entered into multiple
      regression equations with predictor variables. RESULTS: Significant CS-SRM
      regression models emerged for predicting prosthetic use, with timeline cyclical
      (perceptions of symptoms fluctuating) and treatment control (beliefs about
      treatment efficacy) being the most influential variables. Their effects were
      stronger at 6-months than at 1-month. The same variables were influential for
      predicting activity limitations at both 1-month and 6-months. Emotional
      representations (distressing thoughts) were also influential at 1-month.
      CONCLUSIONS: Knowledge of how psychological variables determined prosthetic use
      and activity limitations is valuable because it raises the prospect of being able
      to identify patients whose psychological profiles render them more at risk of not
      rehabilitating successfully with a prosthesis, in this case those who perceived
      symptoms as fluctuating and treatment to be ineffective. Such information could
      also inform the formulation of elements of psychological care aimed at increasing
      the number of patients making effective use of their prosthesis and achieving
      improved activity post-discharge from hospital.

PMID- 18825577
TI  - Perceived parenting style, self-esteem and psychological distress in adolescents
      with heart disease.
AB  - The aim of the study was to assess the relationships between perceived parenting
      style, depressed mood, anxiety and self-esteem in adolescents with heart disease
      compared with healthy adolescents. Forty-five adolescents, aged 12-18 with
      congenital or acquired heart disease and 50 healthy age-matched adolescents
      answered perceived parental behaviour, self-esteem, depressed mood and anxiety
      questionnaires. The study group reported higher perceived acceptance and lower
      perceived parental control than healthy adolescents, but similar levels of
      depressed mood, anxiety and self-esteem. Fischer's r-to-z transformation and
      regression analyses showed different associations between perceived parenting
      style and depressed mood, anxiety and self esteem. In the study group, higher
      perceived parental acceptance was associated with lower depressed mood and higher
      self-esteem, whereas these associations were not significant in the control
      group. In the control, but not the study group, higher perceived parental control
      was associated with lower depressed mood and lower anxiety. Parenting style
      proved to exert a differential effect on adolescents with and without heart
      disease. For the former, perceived parental acceptance had a more substantial
      effect on psychological well-being than perceived parental control. Professionals
      caring for these adolescents should be aware of the special importance of
      parenting style on the well-being of adolescents with heart disease, and address
      this issue in the clinical setting with the patients and their parents.

PMID- 18825578
TI  - Predictors of intentions to perform six cancer-related behaviours: roles for
      injunctive and descriptive norms.
AB  - This study reports an application of the integrative model to the prediction of
      intentions to engage in three cancer screening behaviours (mammogram, colonoscopy
      and PSA test) and three healthy lifestyle behaviours (exercising, eating fruits
      and vegetables, and controlling ones diet to lose weight). We examined the roles
      of attitudes, perceived behavioural control, injunctive norms (what important
      others think one should do), and descriptive norms (perceptions of what others
      do) as predictors of participant's intentions to engage in each behaviour.
      Results indicated that injunctive norms were the strongest predictors of prostate
      and colon cancer screening intentions and contributed significantly to the
      prediction of intentions to get a mammogram. In contrast, injunctive norms
      contributed relatively little to the prediction of lifestyle behaviours, but were
      strongly predictive of intentions to eat fruits and vegetables. Implications for
      designing behaviour-specific communications and interventions are discussed.

PMID- 18825579
TI  - A 1-year follow-up of an experimental study of a self-management arthritis
      programme with an added exercise component of clients with osteoarthritis of the
      knee.
AB  - The aim was to assess the self-efficacy and health outcomes of an adopted
      Arthritis Self-Management Programme (ASMP) among osteoarthritic knee sufferers in
      Hong Kong at 1 year. An experimental study with 95 participants assigned randomly
      to the intervention (n=45) or control group (n=50). Seventy-seven (81.1%)
      participants joined at least one out of three follow-ups in the 12 month period.
      Participants in the intervention group received a 6-week ASMP with an added
      exercise component in two general clinics. Outcome measures included arthritis
      self-efficacy (ASE) and health outcomes including pain and fatigue rating, self
      rated health, daily activities limitation and number of unplanned arthritis
      related medical consultations. Mean change (12 months minus baseline) and the
      effect size of the outcome measures were calculated by Mann-Whitney U test and
      nQuery Advisor 4.0. At 12 months, there were significant reductions of current
      pain (p=0.0001), pain at night (p=0.001), pain during walking (p=0.01) and number
      of unplanned arthritis-related medical consultations (p=0.03) and a significant
      increase in ASE for pain (p=0.01) and other symptoms (p=0.02) and self-rated
      health (p=0.04) among the intervention group but not for the control group.
      However, there were similarities in outcome measures of pain while switching from
      a sitting to a standing position, fatigue rating and physical functional
      limitation (p=0.15; p=0.22 and p=0.91, respectively) for both groups. Our
      findings add to the evidence that the modified arthritis empowering programme
      improved perception of control of osteoarthritis and three health outcomes after
      12 months of treatment.

PMID- 18825580
TI  - Do government brochures affect physical activity cognition? A pilot study of
      Canada's physical activity guide to healthy active living.
AB  - Health Canada has published national physical activity (PA) guidelines, which are
      included in their 26-page Physical Activity Guide to Healthy Active Living
      (CPAG). To date, the use of CPAG as a motivational instrument for PA promotion
      has not been evaluated. The purpose of this study was to determine whether
      reading CPAG 1) increased motivational antecedents to engage in regular PA, and
      2) increased regular PA intention and behaviour over 1 month. Participants
      included 130 randomly sampled Canadian adults (18 years or older) who were
      randomly mailed pack ages consisting of either 1) a questionnaire and a copy of
      CPAG, or 2) a questionnaire. Questionnaire items pertained to participants'
      sociodemographics, previous PA behaviours (Godin Leisure-Time Questionnaire) and
      PA motivation (theory of planned behaviour). Participants were then sent a follow
      up questionnaire pertaining to their PA behaviours throughout the previous month.
      Results revealed significant interactions between the guide condition and
      previous activity status on instrumental behavioural beliefs about strength
      activities and subjective norms about endurance activities (p < 0.05), but all
      other factors were not significantly different. It was concluded that among
      previously inactive people, receiving this guide may change some
      informational/motivational constructs, but key motivational antecedents
      (affective attitude, perceived behavioural control) and outcomes (intention,
      behaviour) seem unaffected.

PMID- 18825581
TI  - Social support group attendance is related to blood pressure, health behaviours,
      and quality of life in the Multicenter Lifestyle Demonstration Project.
AB  - Changes in coronary risk factors, health behaviours, and health-related quality
      of life (HRQOL) were examined by tertiles of social support group attendance in
      440 patients (21% females) with coronary artery disease. All patients
      participated in the Multicenter Lifestyle Demonstration Project (MLDP; eight
      hospital sites in the USA), an insurance-covered multi-component cardiac
      prevention program including dietary changes, stress management, exercise and
      group support for 1 year. Significant improvements in coronary risk factors,
      health behaviours, and HRQOL were noted at 1 year. Several of these improvements
      (i.e. systolic blood pressure, health behaviours, HRQOL) were related to social
      support group attendance, favoring those who attended more sessions. The
      associations between support group attendance to systolic blood pressure and to
      four HRQOL subscales (bodily pain, social functioning, mental health, and the
      mental health summary score) remained significant when controlling for changes in
      health behaviours, but dropped to a non-significant level for the HRQOL subscales
      'physical functioning', 'general health' and 'role-emotional'. These results
      suggest an independent relationship of social support group attendance to
      systolic blood pressure while improvements in quality of life may be in part due
      to improved health behaviours facilitated by increased social support group
      attendance.

PMID- 18825582
TI  - An innovative framework for psychosocial assessment in complex mental capacity
      evaluations.
AB  - This study describes an innovative tool developed by the Regional Capacity
      Assessment Team (RCAT) to assess unique psychosocial factors related to capacity
      evaluations. Capacity is a socio-legal construct entailing the ability to
      understand choices, appreciate consequences and follow through (or direct a
      surrogate) with chosen options. RCAT's targeted psychosocial assessment includes
      medico-legal factors, social history and supports, coping skills,
      religious/cultural factors and risk of abuse. RCAT completes the psychosocial
      assessment to determine whether a full capacity assessment is required (referral
      disposition) and to determine the impact of an adult's social functioning on
      their decision-making capacity (capacity determination). RCAT's psychosocial
      assessment protocol was developed after a comprehensive literature review of
      capacity assessment and incorporates recommended practices in geriatric social
      work and psychology. This study will synthesise the pertinent literature, discuss
      cultural interviewing processes significant to capacity, caregiver assessment and
      describe the tool itself. Suggestions for future research and appropriate
      implementation of this tool are provided.

PMID- 18825583
TI  - Reducing AIDS-related stigma in developing countries: the importance of theory-
      and evidence-based interventions.
AB  - In many developing countries persons living with HIV and AIDS experience strong
      stigma and discrimination, and AIDS-related stigma has an enormous negative
      impact on their social relationships, access to resources, and psychological well
      being. Moreover, AIDS-related stigma hampers HIV-related health promotion,
      including voluntary HIV counselling and testing. In this article, we will argue
      that programs to reduce AIDS-related stigma are most likely to be effective if
      these programs are based upon thorough needs assessments, theory- and evidence
      based intervention strategies and collaborative planning. A protocol for health
      promotion programs design is outlined. Furthermore, psychosocial correlates of
      AIDS-related stigma in developing countries, social-psychological theories that
      might be useful in designing intervention strategies to reduce stigmatisation and
      successful elements of previous interventions aimed at stigma reduction are
      discussed. It is concluded that psychological theory does provide guidelines for
      the development of stigma-reducing intervention programs, but that such programs
      can only be effective when based upon context-specific needs assessment and
      collaborative planning.

PMID- 18825584
TI  - Changing perception of average person's risk does not suffice to change
      perception of comparative risk.
AB  - The direct method of assessing "unrealistic optimism" employs a question of the
      form, "Compared with the average person, what is the chance that event X will
      occur to you?" It has been proposed that when individuals construct their
      responses to this question (direct-estimates) they focus much more strongly on
      estimates of their own risk (self-estimates) than on estimates of the average
      person's risk (other-estimates). A challenge to this proposal comes from findings
      that interventions that alter other-estimates also change direct-estimates.
      Employing a novel intervention technique, we tested the possibility that such
      interventions may indirectly also change self-estimates and that this is what
      accounts for their effect on direct-estimates. Study 1 (n = 58) showed that an
      intervention which was designed to (and did) affect other-estimates also affected
      self-estimates, while Study 2 (n = 101) showed that it affected direct-estimates.
      Study 3 (n = 79) confirmed that we could modify the intervention so as to
      maintain the effect on other-estimates, but eliminate that on self-estimates.
      Study 4 (n = 112) demonstrated that when this was done, there was no longer any
      effect on direct-estimates. The findings are consistent with the proposal that
      direct-estimates are constructed largely just out of self-estimates. Implications
      for heath education programs are discussed.

PMID- 18825585
TI  - Associations between social capital and health status in an Australian
      population.
AB  - This study investigated the association between social capital and health related
      quality of life in a sample of Australian adults. Information was collected from
      a sample of adults in Queensland, Australia relating to health status, health
      related quality of life and related social determinants of health by computer
      assisted-telephone-interview survey. Significant associations were observed
      between social capital and physical health when adjusting for selected
      demographic measures. No significant association was observed between social
      capital and mental health. The research produced equivocal results regarding the
      associations between social capital and the selected measures of health-related
      quality of life. Evidence is presented in support of the association between
      social capital and physical health status, whereas no associations were observed
      between mental health status and social capital. The role and relationship
      between health and social capital remains elusive. More work is required to
      clearly support social capital's role in physical and mental health and well
      being.

PMID- 18825586
TI  - The course of depression 10-weeks post-acute coronary syndrome: assessment using
      the cardiac depression visual analogue scale.
AB  - This study investigated depressed mood post-acute coronary syndrome in an
      Australian sample using the Cardiac Depression Visual Analogue Scale (CD-VAS),
      which was developed to assess the depression-related symptoms of reduced
      pleasure, memory, activity, future pessimism, increased irritation and sleep
      problems. The Beck Depression Inventory-II, the Cardiac Depression Scale (CDS)
      and a demographic medical questionnaire were administered at 2 weeks post-ACS to
      an initial sample of 13 female and 45 male participants whose mean age was 59.16
      (SD=11.13) years (range 38-79). Depressed and non-depressed participants,
      determined by the CDS, then kept a CD-VAS diary between 2 and 12 weeks. 32
      participants kept the diary for the entire 10 weeks. Total CD-VAS scores remained
      elevated in the depressed group for the entire period. The groups differed on the
      Pleasure, Memory and Future items for a total of 6, 6 and 5 weeks, respectively,
      and differed on the Activity item only at 1, 3 and 5 weeks. No group differences
      were seen in the Irritation or Sleep items. Within the depressed group, the only
      CD-VAS items that differed from each other across time were Irritation and
      Activity. Further, the Sleep, Irritation and Activity items had a significant
      time effect. These results indicate that although overall depression, as measured
      by the CD-VAS, remained elevated in the depressed group, there were key
      differences in recovery rates of specific depression-related symptoms. These
      differences could be useful indicators in the treatment of depression post-ACS.

PMID- 18825587
TI  - Predictors of fatigue over 1 year among people with rheumatoid arthritis.
AB  - Fatigue is a systemic feeling of exhaustion that is a common symptom of many
      chronic illnesses, including the autoimmune inflammatory disease rheumatoid
      arthritis (RA). We examined predictors of levels of fatigue among people with RA
      using Leventhal's Common-Sense Model (CSM), which states that cognitive
      representations of an illness spur (or halt) people's efforts to cope and thereby
      influence outcomes of the illness. Our use of the CSM was designed in the light
      of evidence in the literature specific to fatigue in RA. Current fatigue was
      reported on a 100 mm visual analogue scale (with anchors "No fatigue" and
      "Unbearable fatigue") by 114 people (73.7% women) with RA at baseline and 1 year
      later. Baseline employment status, pain, impact of disability, sleep disruption
      frequency, depressed mood, perceptions of consequences, arthritis self-efficacy
      and attempts to cope by praying/hoping were also self-reported. Duration of RA
      and a haematological measure of systemic inflammation (erythrocyte sedimentation
      rate; ESR) were obtained from hospital records. Unexpectedly, RA duration did not
      predict fatigue after 1 year, although lower baseline inflammation did
      (controlling for baseline fatigue and other disease impact variables). This may
      be due to sampling flares of RA at baseline. Baseline perceptions that RA has
      severe consequences and is uncontrollable also predicted greater fatigue after 1
      year but this relationship was not mediated by praying/hoping. Targeted
      psychological care to modify perceptions of severe consequences may therefore
      improve later fatigue for people with RA even when the condition is longstanding,
      but the mechanisms of any benefit require further investigation.

PMID- 18825588
TI  - Diversity of mucosa-associated microbiota in active and inactive ulcerative
      colitis.
AB  - OBJECTIVE: Recent findings indicate that bacteria play an important role in the
      pathogenesis of inflammatory bowel disease (IBD). However, the exact role of
      bacteria in ulcerative colitis (UC) has still to be elucidated. The objective of
      the study was to investigate the potential differences in the intestinal
      microbiota between patients with UC and control subjects, using terminal
      restriction fragment length polymorphism (T-RFLP) analysis of the mucosa
      associated microbiota from UC patients and non-IBD controls. MATERIAL AND
      METHODS: Nine active UC patients and 11 non-IBD controls were included in the
      study. Seven patients with active UC who entered into the inactive phase after
      antibiotic combination treatment were also classified as patients with inactive
      UC. Mucosa-associated microbiota was compared between non-IBD controls and UC
      patients using T-RFLP analysis. Microbiota in both the active and inactive phase
      was also analyzed in UC patients receiving antibiotic treatment. RESULTS: T-RFLP
      patterns of mucosa-associated microbiota differed between active UC patients and
      non-IBD controls. Microbial compositions of active UC patients were significantly
      less diverse. The difference resulted from loss of commensals. From the viewpoint
      of disease activity before and after antibiotic combination treatment, T-RFLP
      patterns were also different between the active and inactive phases in the
      identical patients. Inactive UC patients possessed more diverse microbial
      compositions. No specific terminal restriction fragments were observed in UC
      patients. CONCLUSIONS: T-RFLP analysis showed that the mucosa-associated
      microbiota of patients with active UC differed from that of non-IBD controls.
      Active UC patients possessed significantly fewer diverse microbial compositions.

PMID- 18825589
TI  - The effect of deception on motor cortex excitability.
AB  - Although a number of recent neuroimaging studies have examined the relationship
      between the brain and deception, the neurological correlates of deception are
      still not well understood. The present study sought to assess differences in
      cortical excitability during the act of deception by measuring motor evoked
      potentials (MEPs) during transcranial magnetic stimulation (TMS). Sports fanatics
      and low-affiliation sports fans were presented with preferred and rival team
      images and were asked to deceptively or honestly identify their favored team.
      Hemispheric differences were found including greater excitability of the left
      motor cortex during the generation of deceptive responses. In contrast to current
      physiological measures of deception, level of arousal was not found to
      differentiate truthful and deceptive responses. The results are presented in
      terms of a complex cognitive pattern contributing to the generation of deceptive
      responses.

PMID- 18825590
TI  - Comparison of the quick drinking screen and the alcohol timeline followback with
      outpatient alcohol abusers.
AB  - OBJECTIVE: A recent study comparing the Quick Drinking Screen (QDS) with the
      Timeline Followback (TLFB) found that in a nonclinical population of problem
      drinkers both measures produced reliable summary measures of drinking. The
      current study was designed to replicate these findings with a clinical population
      of alcohol abusers. The data were collected over three years (2004-2006). METHOD:
      Participants were 124 alcohol abusers who voluntarily enrolled for outpatient
      treatment. Over half (52.4%) were female with an average age of almost 40 years.
      About a third were married, had completed university, and a quarter were
      unemployed and nonwhite. Participants reported having a drinking problem for an
      average of 8.3 years, and reported drinking on about 5 days per week, averaging
      six drinks per drinking day. On two different occasions, they responded to two
      different sets of questions about their alcohol use. The instruments were: (a)
      the Quick Drinking Screen (QDS), a summary drinking measure, administered by
      telephone prior to the assessment; and (2) the TLFB self-administered by computer
      at the assessment. RESULTS: As in a previous study, this study found that the QDS
      and the TLFB, two very different drinking measures, collected similar aggregate
      drinking data for four drinking variables in a clinical sample of alcohol
      abusers. CONCLUSIONS: When it is not necessary or not possible to gather detailed
      drinking data, the QDS produces reliable brief summary measures of drinking for
      problem drinkers. Generalization to nonclinical samples awaits further research.

PMID- 18825591
TI  - The role of alcohol use in emergency department episodes.
AB  - This study investigates the association between alcohol use and emergency
      department (ED) utilization in the United States using nationally representative
      data from the 2001 National Health Interview Survey (N = 33,326). Estimates from
      our probit models indicate that among men, current drinkers are less likely to
      have visited the ED in the past year than former drinkers. Among women, lifetime
      abstainers are less likely than current drinkers to have had an ED episode.
      Finally, frequency of binge drinking significantly increases the likelihood of ED
      visits for men. The results suggest that focusing solely on problem drinking
      provides a limited perspective.

PMID- 18825592
TI  - Immunohistochemical and ultrastructural changes in the brain in probable adult
      glycogenosis type IV: adult polyglucosan body disease.
AB  - Glycogenosis type IV is caused by a deficiency of glycogen branching enzyme
      (alpha-1,4 glucan 6-transglucosylase). Adult polyglucosan body disease (APBD) may
      represent a neuropathological hallmark of the adult form of this storage disease
      of the central nervous system. We analysed a case of a 45-year-old unconscious
      woman who died three days after admission to the hospital. Neuropathological
      examination revealed massive accumulation of polyglucosan bodies (PBs) in the
      cortex and white matter of the whole brain. PBs were located in the processes of
      neurons, astrocytes and microglial cells. The storage material in the cytoplasm
      of neurons and glial cells was visible as fine granules. Ultrastructurally, PBs
      consisted of non-membrane-bound deposits of branched and densely packed
      filaments, measuring about 7-10 nm in diameter, typical of polyglucosan bodies.
      APBD patients develop upper and lower neuron disease and dementia, probably
      secondary to the disruption of neuron and astrocyte functions.

PMID- 18825593
TI  - Neuroblastoma and opsoclonus-myoclonus-ataxia syndrome--clinical and pathological
      characteristics.
AB  - INTRODUCTION: Opsoclonus-myoclonus-ataxia (OMA) syndrome is the most common
      paraneoplastic neurological syndrome in childhood. MATERIALS AND METHODS: We
      reviewed the literature and reported on clinical and pathological characteristics
      of four children with OMA and peripheral neuroblastic tumours. In two of the
      children the onset of neurological symptoms was connected with a vaccination and
      in one with viral infection. The suprarenal gland was the primary localization of
      the tumour in 3 of the children and in one the tumour was located in the
      retroperitoneal area. All cases were in stage II or III of the disease, with no
      metastases or MYCN amplification. The group included two ganglioneuroblastomas,
      one ganglioneuroma and one differentiating neuroblastoma. The tumours were
      characterized by the presence of lymphocytic infiltrations with lymphadenoplasia.
      Immunohistochemical analysis of inflammatory infiltrations revealed mixed type
      populations of lymphocytes with prevalence of the cytotoxic type (CD8 and CD56
      positive cells). The participation of dendritic cells and macrophages was also
      detected. All patients were treated by surgery alone or with adjuvant
      chemotherapy with a positive outcome. In 3 cases persistent neurological
      disorders were observed with exacerbations during infections. CONCLUSION: In some
      patients the onset of OMA is related to vaccination or infection. Children with
      OMA and neuroblastoma despite a good oncological prognosis often present
      permanent neurological and developmental deficits. The inflammatory infiltrations
      within the tumours are combined, with predominant participation of cytotoxic
      cells.

PMID- 18825594
TI  - Asymptomatic and symptomatic glial cysts of the pineal gland.
AB  - Glial cysts of the pineal gland are benign and mostly asymptomatic incidental
      lesions found in the brain MRI or at autopsy examinations. In rare cases pineal
      cysts become symptomatic and require surgical intervention. Symptomatic glial
      cysts may be clinically and radiologically indistinguishable from cystic
      neoplasms of the pineal region; therefore, histopathological diagnosis is
      critical for further prognosis and therapy in operated patients. In this paper we
      present detailed histopathological characteristics of symptomatic glial cysts in
      2 surgical cases and of asymptomatic cysts of the pineal gland found at random in
      3 autopsy cases. Both surgical patients, a 19-year-old girl and a 17-year-old
      boy, presented with severe headaches, associated with syncope in one case and
      insomnia in the second one. Preoperative MR imaging suggested tumour of the
      pineal gland in case no. 2. Histopathological and immunohistochemical examination
      of the specimens from both surgical and all autopsy cases revealed a
      characteristic pattern of cystic structures within the pineal gland, surrounded
      by layers of a dense fibrillar glial tissue and pineal parenchyma, consistent
      with non-neoplastic glial cysts. Although histopathological findings in
      asymptomatic and symptomatic cysts are essentially the same, the cyst in surgical
      case 1 was unilocular and partly lined with ependymal cells, whereas the cysts in
      other cases were multilocular, comprising cavities of various size, formed in the
      central part of gliotic tissue or directly within the pineal parenchyma, and
      lacked ependymal lining. Possible pathophysiological and clinicopathological
      significance of some morphological variants of pineal glial cysts is discussed.

PMID- 18825595
TI  - Nuclear architecture remodelling in cardiomyocytes with lamin A deficiency.
AB  - We analysed the architecture of cardiomyocyte nuclei lacking lamin A activity in
      three patients with dilated cardiomyopathy. The diagnosis was established on the
      basis of clinical and electrophysiological examinations, chest radiography and
      electrocardiography. An ultrastructural study of affected cardiomyocytes showed
      dramatic alterations in nuclear distribution and organization affecting nuclear
      shape, lamina structure, chromatin and nuclear interior organization. The most
      specific hallmark of nuclei with lamin A deficiency was the reorganization of the
      nuclear interior, the appearance of a various number of mitochondria within the
      nuclear matrix, and focal or total lack of nuclear membrane.

PMID- 18825596
TI  - Efficacy of remote ischaemic preconditioning for spinal cord protection against
      ischaemic injury: association with heat shock protein expression.
AB  - INTRODUCTION: We aimed to determine the efficacy of remote ischaemic
      preconditioning in the hind limb of rats for ischaemic damage of the spinal cord
      through neurological and histological investigation and examination of heat shock
      proteins (HSP). MATERIAL AND METHODS: Thirty male Sprague-Dawley rats were
      divided into three groups as Group 1 (control group, n=10), Group 2 (ischaemia
      control group, n=10), and Group 3 (remote ischaemia preconditioning group, n=10).
      The right lower limb of the rats in the study group was compressed with a
      tourniquet for three cycles of ten-minute ischaemia followed by ten-minute
      reperfusion. After a period of 8 hours, the peritoneal cavity was accessed
      through a midline vertical incision. The abdominal aorta was clamped between the
      origin of the renal arteries and the iliac arteries for 45 minutes and spinal
      cord ischaemia was induced. The same procedure of abdominal aorta clamping was
      performed in the control group without creating leg ischaemia. The rats were
      evaluated for neurological parameters at 24 and 48 hours. At the end of this time
      period, all rats were sacrificed and the spinal cords were stained for
      determination of HSP and histopathological classification. For
      immunohistochemical evaluation, the samples were analyzed according to the degree
      of staining with HSP70 rabbit antibody. RESULTS: After completing the
      neurological examinations and histological evaluations, we determined the spinal
      cords of the animals in the sham group to be completely normal. The post
      operative neurological examination scores of Group 3 at 24 and 48 hours were
      significantly higher than scores measured in the other two groups. There were
      seven rats with HSP expression and this was detected in animals pretreated with
      remote ischaemic preconditioning. There were also two rats in Group 2 with HSP
      expression. CONCLUSION: Our results show that production of transient remote
      ischaemia preconditioning in the lower extremities reduces damage in the spinal
      cord secondary to ischaemia probably by the increase of HSP.

PMID- 18825597
TI  - Apoptotic death of cortical neurons following surgical brain injury.
AB  - Unilateral surgical brain injury of the rat is a model of surgery-related brain
      damage of humans. Our preliminary experiments showed two phenomena within the
      damaged cortical region of rat brain. Those were: degeneration and death of
      neurons and massive gliosis. In the present study we aimed to investigate the
      mechanisms of neuronal death following brain injury and to characterize responses
      of glial cells to the damage. We analyzed the morphological changes and
      alterations of immunochemical profile of cells localized in the brain areas
      adjacent to the lesion. Our data show the massive neuronal death following the
      lesion. Neurons undergo necrosis and apoptosis, but on the 4th day following the
      operation apoptosis prevails. Apoptotic cells showed heavy immunostaining for
      proapoptotic Bax and caspase 3. This result suggests the involvement of these
      proteins in neuronal apoptosis in our experimental model. Neuronal death is
      accompanied by the induction of astrogliosis in the perilesional cortical area.
      Astrocytes became hypertrophic. We did not detect any dying astrocytes at the
      investigated time point, but there is a possibility that apoptosis may occur in
      astroglia during another time period following the damage. This question requires
      further studies in our experimental model.

PMID- 18825598
TI  - Giant cell ependymoma of the spinal cord and fourth ventricle coexisting with
      syringomyelia.
AB  - This report presents a case of widespread intramedullary giant cell ependymoma
      arising from the central canal of the C4 segment of the spinal cord in a 28-year
      old man admitted to hospital with tetraplegia and signs of increased intracranial
      pressure, eight months after surgical spinal cervical decompression without
      tetraplegia improvement. Magnetic resonance imaging and autopsy revealed a tumour
      extending from segment C3/C4 of the spinal cord to the lower half of the fourth
      ventricle with coexisting syringomyelia. This slow-growing ependymoma of low
      grade malignancy exhibited unusual morphology as well as degenerative and
      ischaemic changes. All intramedullary and ventricular tumour segments featured
      coexistence of two forms of neoplastic cell, classic ependymomal and pleomorphic
      multinucleated giant cells. The morphological diagnostic criteria of unusual
      giant-cell variant of ependymoma and tumour-related syringomyelia in adults are
      discussed, based on the presented case and a review of the literature.

PMID- 18825599
TI  - Brain and cerebellar hemidysplasia in a case with ipsilateral body dysplasia and
      suspicion of CHILD syndrome.
AB  - CHILD syndrome is an acronym for Congenital Hemidysplasia with Ichthyosiform
      nevus and Limb Defects. This is an X-linked dominant disorder affecting females
      with early lethality in hemizygous males. The clinical features are congenital
      hemidysplasia with ichthyosiform erythroderma and ipsilateral hypoplasia of limbs
      and other parts of the skeleton as well as defects of the brain, heart, kidney
      and lung. CHILD syndrome is caused by mutations in the NSDHL (steroid
      dehydrogenase-like protein) gene at Xq28, which affects cholesterol biosynthesis.
      A female premature newborn with left side body hemidysplasia and ipsilateral
      defects of the skin, visceral organs and brain is reported. Analysis of child DNA
      isolated from skin fibroblasts showed missense mutation c.1046A>G;PpY349C in the
      NSDHL gene that could cause the phenotype.

PMID- 18825600
TI  - [Information fur unsere Autoren - Ab sofort Manuskripteinreichung via Internet.]

PMID- 18825601
TI  - [Arzneitherapiesicherheit - Strategien zur Vermeidung unerwunschter
      Arzneimittelnebenwirkungen.]

PMID- 18825602
TI  - [Sorgfaltsanforderungen an Aufklarung (OLG Celle, Urteil v. 25.06.2001, AZ: 1 U
      48/00) - Tod des Patienten nach laparoskopischer Hernioplastik beidseits.]

PMID- 18825603
TI  - Kurt T. Barnhart, M.D., M.S.C.E.

PMID- 18825604
TI  - Early pregnancy disorders: an update and eye to the future. Preface.

PMID- 18825605
TI  - Ultrasound criteria for diagnosis of early pregnancy failure and ectopic
      pregnancy.
AB  - Early pregnancy failure and ectopic pregnancy are common clinical diagnoses for
      which ultrasound can provide useful information. This review explores the use of
      ultrasound to diagnose early pregnancy failure and ectopic pregnancy. By
      documenting the developmental milestones of early normal pregnancy using
      ultrasound, clinicians can distinguish normal from abnormal intrauterine
      pregnancies. An early pregnancy failure can be diagnosed by the absence of a
      visible yolk sac with a mean sac diameter of 13 mm; the absence of a visible
      embryo with a mean sac diameter of 20 [corrected] mm; the absence of cardiac
      motion with an embryo measuring 5 mm or more in maximal length; or the presence
      of an empty amnion. In most settings, documentation of a normal intrauterine
      pregnancy effectively eliminates the possibility of ectopic pregnancy. The
      presence of an adnexal mass in the absence of an intrauterine gestational sac may
      indicate an ectopic pregnancy.

PMID- 18825606
TI  - The use of serial human chorionic gonadotropin levels to establish a viable or a
      nonviable pregnancy.
AB  - Measurement of serial human chorionic gonadotropin (hCG) concentrations
      facilitates the diagnosis of normal or abnormal early gestation, as deviations
      from expected rates of rise or decline prompt intervention and/or treatment of
      abnormal pregnancies. Recently, the expected rise in hCG levels for normal
      intrauterine pregnancies (IUPs) was well characterized, and based on a 95%
      confidence interval, it was determined that the slowest rise in a normal IUP was
      53% in 2 days. When the hCG level is decreasing, it is clear that the pregnancy
      is not viable. The management of such cases consists of observation or
      intervention. The rate of decline associated with nonviable pregnancies that
      resolved with expectant management has been described, with a faster decline
      observed with higher hCG levels at presentation. A rate of decline that is slower
      than 21 to 35% in 48 hours suggests the presence of retained trophoblastic tissue
      or an ectopic pregnancy and indicates the need for intervention to achieve a
      definitive diagnosis. While there is no consistent pattern of serial hCG levels
      characterizing ectopic pregnancies, the majority of patients ultimately diagnosed
      with ectopic pregnancy will exhibit rates of rise or decline that are outside the
      "normal" range as defined by the established curves.

PMID- 18825607
TI  - Miscarriage and its associations.
AB  - Despite many years of study, abnormal chromosome number remains the most common
      and well-documented cause of miscarriage. Nonchromosomal factors that have been
      associated with miscarriage are many and include endocrine abnormalities,
      anatomic abnormalities, inherited and acquired thrombophilia, environmental
      exposures, immunologic factors, and others. This article attempts to provide a
      brief overview and critique of the frequently reported factors. In addition, we
      call attention to the fact that, to be most helpful, modern studies of
      miscarriage need to provide details about the sonographically determined
      gestational age and fetal anatomic development prior to or at the time of
      pregnancy loss. Such information will be critical in helping to sort out which
      miscarriage-associated factors are more relevant at which stage of fetal
      development.

PMID- 18825608
TI  - Medical management of early pregnancy failure: how to treat and what to expect.
AB  - Medical management is gaining acceptance as a treatment option for women with
      early pregnancy failure (EPF). We reviewed randomized trials comparing
      misoprostol for EPF with surgical (dilation and curettage) or expectant
      management. Overall, approximately 85% of women with EPF can expect complete
      uterine evacuation after one or two doses of 600 or 800 microg misoprostol
      without surgery. Medical management is safe. As with surgical therapy, serious
      complications are rare. Women undergoing medical management of EPF may expect
      moderate pain and bleeding for several days, which may persist for 2 weeks or
      longer. Side effects associated with misoprostol are common; however,
      acceptability of medical management remains high.

PMID- 18825609
TI  - Medical management of early pregnancy failure: efficacy.
AB  - Early pregnancy failure is a common pregnancy complication. This article reviews
      the efficacy of medical management of early pregnancy failure. Nonsurgical
      treatments, including expectant and medical management, are reasonable
      alternatives to surgical management depending on the clinical situation and the
      patient's requests. Possible regimens in medical management of early pregnancy
      failure include misoprostol alone or mifepristone in conjunction with
      misoprostol. However, many studies of medical management may underestimate
      success rates due to inconsistent inclusion criteria, different dosing regimens,
      and varying definitions of failed treatment. Clinicians need to understand the
      range of efficacy of these regimens to provide appropriate counseling to
      patients.

PMID- 18825610
TI  - The association of in vitro fertilization and perinatal morbidity.
AB  - In recent years, there has been increasing concern regarding the safety of in
      vitro fertilization (IVF) because of the potential health impact on these
      infants. Multiple pregnancy contributes the vast majority of morbidity associated
      with IVF and, initially, many thought that adverse outcomes after IVF were solely
      attributable to the high incidence of twin pregnancies. More recently, multiple
      studies have suggested that IVF singleton pregnancies may be at increased risk
      for preterm birth, low birth weight, congenital anomalies, perinatal mortality,
      and several other pregnancy-related complications compared with unassisted
      singleton pregnancies. We have focused this review on the increased risk of
      adverse outcomes in IVF singleton conceptions compared with that of unassisted
      conceptions. The available evidence evaluating the association between IVF and
      low birth weight, preterm delivery, placental abruption, preeclampsia, congenital
      anomalies, and perinatal mortality in singleton pregnancies is summarized. In
      addition, data reporting an increased risk of congenital and chromosomal
      anomalies after IVF are presented.

PMID- 18825611
TI  - Fetal origins of perinatal morbidity and/or adult disease.
AB  - The developmental origin of health and disease hypothesis holds that events
      occurring during the early development of an individual and specifically during
      intrauterine life have profound consequences on future health. Low birth weight,
      a marker of intrauterine stress, has been linked to predisposition to
      hypertension, cardiovascular diseases, diabetes, and stroke. The compelling
      animal evidence and significant human epidemiologic data to support this
      conclusion is reviewed. In addition, we propose that early embryo manipulation
      and culture that occur during use of assisted reproductive technologies may
      represent a stressful event that could be associated with future health problems.
      The effects of embryo culture on early development and gene expression and
      methylation status is reviewed and discussed.

PMID- 18825612
TI  - Modulation of insulin concentrations and metabolic parameters in obese patients
      by -55CT polymorphism of the UCP3 gene secondary to two hypocaloric diets.
AB  - Decreased expression or function of UCP3 could reduce energy expenditure and
      increase the storage of energy. The aim of our study was to investigate the
      influence of -55CT polymorphism of the UCP3 gene on insulin concentrations and
      metabolic parameters secondary to two hypocaloric diets in obese patients. A
      population of 131 obese (body mass index >30), nondiabetic outpatients was
      analyzed in a prospective way. Before and after 2 months on two different
      hypocaloric diets, bipolar electrical bioimpedance, blood pressure measurement,
      serial assessment of nutritional intake with 3 d of written food records, and
      biochemical analysis were performed. The statistical analysis was performed based
      on a dominant model. With diet type I (low fat) and diet type II (low
      carbohydrate) in probands with both wild-type alleles, we observed decreases in
      BMI, weight, fat mass, systolic blood pressure, leptin levels, and insulin
      concentrations. In addition, with diet type II, a decrease in diastolic blood
      pressure, total cholesterol, and triglyceride levels was detected. Secondary to
      diet type I, a decrease in waist circumference and TNF-alpha was observed.
      Carriers of the T variant experienced decreases in BMI, weight, and fat mass on
      both diets, without statistical changes in biochemical parameters. In probands
      with both C alleles, both diets decreased insulin concentrations, blood pressure,
      and leptin concentrations. Weight reduction was similar with C and T alleles,
      independent of macronutrient distribution.

PMID- 18825613
TI  - Effects of fructose and/or fat in the diet on developing the type 2 diabetic-like
      syndrome in CD-1 mice.
AB  - The aim of the present study was to examine the interactions of fructose and fat
      on glucose regulation and lipid metabolism in CD-1 mice. Mice were assigned in
      five groups. The control group was provided with tap water and a gavage of
      vehicle; four experimental groups were treated with 150 g/l fructose solution
      (FS1), fat emulsion (FE), 150 g/l fructose solution and fat emulsion (FS1+FE), or
      70 g/l fructose solution and fat emulsion (FS2+FE) for 12 weeks. At the end of
      the 8th week, both oral glucose tolerance test and insulin tolerance test were
      conducted. Lipid profiles in serum, liver, and red gastrocnemius muscle, and
      serum insulin and glucose concentrations were assessed. The FS1+FE group showed
      combined glucose intolerance (CGI) and decrease of insulin sensitivity. The low
      density lipoprotein cholesterol (LDL-C) concentrations were elevated in all
      experimental groups (p<0.05). The combined diet groups showed statistically
      significant (p<0.01) increase in total cholesterol (TC) level in comparison with
      the control FE (p<0.05), or FS1 (p<0.05) group. Triglyceride levels in liver and
      red gastrocnemius muscle were significantly increased in FE and combined groups.
      In conclusion, combination of FE and 150 g/l fructose solution for 8 weeks led to
      CGI. Fructose enhanced the adverse effect of FE on glucose regulation with
      increasing percentage in the diet. Furthermore, there was a synergistic effect of
      fructose and fat on elevating the serum TC level.

PMID- 18825614
TI  - Noninvasive microcirculatory flap monitoring or implantable doppler probes: only
      an adjunct to clinical assessment for reconstructive microsurgery?

PMID- 18825615
TI  - Bypassing spinal cord injury: surgical reconstruction of afferent and efferent
      pathways to the urinary bladder after conus medullaris injury in a rat model.
AB  - Afferent and efferent nerve function in the atonic bladder caused by conus
      medullaris injury in a rat model was established by intradural microanastomosis
      of the left L5 ventral root (VR) to right S2 VR to restore pure motor-to-motor
      reinnervation coupled with extradural postganglionic spinal nerve transfer of L5
      dorsal root (DR) to S2 DR for pure sensory-to-sensory reinnervation. Early
      function of the reflex arc was evaluated by electrophysiological study, as well
      as by intravesicular pressure measurement and histological examination. The
      results demonstrated that single focal stimulation of the left S2 DR elicited
      evoked potentials at the left vesicular plexus before and after horizontal spinal
      cord damage between the L6 and S4 level. Bladder contraction was successfully
      initiated by trains of stimuli targeting the left L5-S2 DR anastomosis.
      Achievable bladder pressures and amplitude of bladder smooth muscle complex
      action potentials were unchanged before and after induced paraplegia and
      comparable to those of the control. Prominent axonal sprouting was seen in the
      distal part of nerve graft. Both afferent and efferent nerve pathways in the
      atonic bladder can be reconstructed by suprasacral motor-to-motor and sensory-to
      sensory nerve transfer after spinal cord injury in rats. This reconstructive
      strategy has significant potential in clinical application.

PMID- 18825616
TI  - Recipient vessel exposure in the axilla during microvascular breast
      reconstruction.
AB  - Over the years, the favored recipient vessels for microvascular breast
      reconstruction have changed from the thoracodorsal to the internal mammary
      vessels, mainly due to the deep position and poor exposure of the vessels in the
      axilla and all the technical difficulties this reflects. We used the simple
      maneuver of arm adduction during microvascular anastomoses in the axilla and
      compared it with the conventional method of abducted arm regarding the exposure
      of the vessels, the position of the operator and the assistant, and the operative
      time. We found that this innovation considerably improved the exposure of the
      vessels and the operator's position, facilitating easier and faster anastomoses.

PMID- 18825617
TI  - Growth disturbances of the distal tibia after physeal separation--what do we
      know, what do we believe we know? A review of current literature.
AB  - PURPOSE: Although they are the most frequent physeal separations of the lower
      limb, epiphyseal separations (Salter I and II) of the distal tibia are rare
      injuries, peaking in adolescence. Generally they are considered lobe benign
      fractures with a low rate of complications. However, in the literature, concrete
      statements on the incidence of fracture-associated growth disturbances are
      infrequent and inconsistent, even contradictory. MATERIALS AND METHODS: A review
      of textbooks, classical references and recent literature was performed to
      identify the available evidence on distal tibia physeal separations. RESULTS: A
      review of the literature showed that most authors agree that conservative,
      nonoperative treatment is the preferred treatment. But opinions differ on almost
      all essential fundamentals of treatment. Neither the potential for growth
      associated spontaneous correction of posttraumatic axis deviations nor the
      tolerable degree of axial deviations are evaluated homogenously. Opinions also
      vary greatly concerning the frequency of posttraumatic growth disturbances, the
      influence of the mechanism of injury and the amount of primary axial deviation.
      The most consistent statement in the literature is that poor results of both
      closed and open reduction lead to an increasing number of growth disturbances,
      which may include the assumption that not only trauma but operative procedures,
      too, can be the reason for restrictive physeal plate disturbances. CONCLUSIONS:
      There are two major deficiencies in most of the reviewed literature. The first is
      that the numbers of cases reported in each article are low due to the rarity of
      the injury. The second deficiency is that many studies report "physeal injuries"
      but do not clearly distinguish physeal separations (Salter I and II) from
      epiphyseal fractures (Salter III and IV) and transitional fractures, all
      involving the physeal plate, but in completely different ways with completely
      different prognoses. A prospective multicenter study is taking place.

PMID- 18825618
TI  - Is there a role for Helicobacter pylori infection in urological diseases?
AB  - INTRODUCTION: Helicobacter pylori (H pylori) infection is a focus of attention
      nowadays. It has been found to cause gastrointestinal disorders and also extra
      intestinal disorders. The aim of this paper is to explore the role of H pylori in
      urological diseases and to keep urologists up to date in this subject. MATERIALS
      AND METHODS: Medline and PubMed were searched from 1950 to December 2007 for the
      following combined terms: Helicobacter pylori together with urology, urological
      diseases, kidney, kidney cancer, ureter, bladder, bladder cancer, prostate,
      prostate cancer, benign prostatic hyperplasia, urethra, seminal vesicle, testis,
      and testicular cancer. RESULTS: Accumulating evidence is appearing in the
      literature relating H pylori infection to urological diseases. The most obvious
      is the implication of H pylori in inducing chronic cystitis leading to bladder
      lymphoma. In addition, some epidemiological studies have shown significant
      associations between infective chronic prostatitis and prostatic carcinoma.
      CONCLUSION: A simple hypothetical model relating H pylori infection to prostate
      and bladder diseases is proposed to stimulate the collaborative work between the
      urologists and scientists to explore this field which is underinvestigated to
      date. If H pylori is found to have a significant role in urological diseases,
      prevention of bladder and prostate cancers by eradication of H pylori infection
      may become a reality like what happened in the treatment of peptic ulcer disease
      and gastric cancer.

PMID- 18825619
TI  - Lymphocele after kidney transplantation: where are we standing now?

PMID- 18825620
TI  - Effect of thymoquinone on ethylene glycol-induced kidney calculi in rats.
AB  - INTRODUCTION: The aim of this study was to investigate the effects of
      thymoquinone, a major component of Nigella Sativa seeds on ethylene glycol
      induced kidney calculi in rats. MATERIALS AND METHODS: Sixty male Wistar rats
      were randomly divided into 6 groups (intact control, ethylene glycol control, and
      4 experimental groups) and treated for 28 days according to the protocol of the
      study. The rats in experimental groups received ethylene glycol and
      intraperitoneal injection of thymoquinone either from the first day of the study
      or the 15th day, with either doses of 5 mg/kg or 10 mg/kg. Blood and 24-hour
      urine samples were collected at baseline and on day 28. Urine oxalate and citrate
      and serum electrolytes were also measured. On day 29, all rats were decapitated
      and their kidney specimens were studied. RESULTS: On day 28, urine oxalate
      concentration significantly decreased in the experimental groups compared to the
      ethylene glycol group (P < .001). Also, serum calcium levels were significantly
      higher in the experimental groups (P = .001). Calcium oxalate deposits were
      smaller in the experimental groups than the ethylene glycol group. The mean
      number of deposits was lower in these groups, too (P < .001). Treatment with the
      lower dose of thymoquinone was associated with fewer deposits. CONCLUSION:
      Thymoquinone significantly decreased the number and size of calcium oxalate
      deposits in the renal tubules. The dose and duration of treatment, however, does
      not have a linear relation with the outcomes. Further studies on thymoquinone as
      a preventive and therapeutic drug for kidney calculi are suggested.

PMID- 18825621
TI  - Prevalence of symptomatic urinary calculi in Kerman, Iran.
AB  - INTRODUCTION: In a cross-sectional study, we evaluated the prevalence of
      symptomatic urinary calculi in Kerman, Iran. MATERIALS AND METHODS: A total of
      2431 citizens of Kerman were surveyed from September of 2005 to April 2006. The
      study population was selected by cluster method from 5 different areas, and 100
      houses in each area were randomly approached. Questions on the urinary symptoms
      consisted of flank pain, urogenital pain, dysuria or any difficulty in urination,
      and alterations in urine color. Individuals with a suspicion of urinary calculi
      based on their symptoms were evaluated by physical examination, laboratory
      investigations, and plain abdominal radiography. Ultrasonography and intravenous
      urography were done if required to confirm the diagnoses. RESULTS: Of 2431
      individuals, 196 (8.1%) had symptoms in favor of urinary calculus diagnosis, of
      whom 47 (24.0%) had urinary calculi (prevalence of symptomatic urolithiasis was
      1.9%). Of the patients, 35 (74.5%) were underweight. Compared to the other
      participants, the patients with urinary calculus were younger (P = .001) and a
      larger proportion of them had a positive family history of urinary calculi (14.9%
      versus 6.5%; P = .02) and were rug weavers and office employees. Dependency on
      opium and its derivative was significantly more frequent in patients with urinary
      calculi (25.5% versus 0.2%; P = .001). CONCLUSION: This study showed that the
      prevalence of symptomatic urinary calculi in this hot and dry area is relatively
      high. According to our findings, the other factors including specific
      occupations, malnutrition, and substance use may also have influence on the rate
      of urinary calculus formation. Therefore, to prevention and early treatment of
      urinary calculi, evaluation of potential predisposing conditions should be
      considered with special attention to regional factors.

PMID- 18825622
TI  - Cytotoxic effect of saffron stigma aqueous extract on human transitional cell
      carcinoma and mouse fibroblast.
AB  - INTRODUCTION: Saffron has been suggested to have inhibitory effects on tumoral
      cells. We evaluated the cytotoxic effect of aqueous extract of saffron on human
      transitional cell carcinoma (TCC) and mouse non-neoplastic fibroblast cell lines.
      MATERIALS AND METHODS: Human TCC 5637 cell line and mouse fibroblast cell line
      (L929) were cultivated and incubated with different concentrations of aqueous
      extract of saffron stigma (50 microg/mL to 4000 microg/mL). Cytotoxic effect of
      saffron was evaluated by morphologic observation and 3-(4,5-dimethylthiazol-2-yl)
      2,5-diphenyltetrazolium bromide colorimetric assay after 24, 48, 72, and 120
      hours in each cell line. RESULTS: After 24 hours, morphological observations
      showed growth inhibitory effects at saffron extract concentrations higher than
      200 microg/mL for L929 cells and at concentrations of 50 microg/mL to 200
      microg/mL for the TCC cells. These changes became more prominent after 48 hours.
      However, significant growth inhibitory effects of the extract were shown at
      concentrations of 400 microg/mL and 800 microg/mL. Higher concentrations of
      saffron correlated inversely with cell population of both cell lines. Significant
      reduction of the survived cells was seen at concentrations of 400 microg/mL and
      2000 microg/mL for TCC and L929 cell lines, respectively. After 120 hours,
      decrease in the percentage of survived cells at higher concentrations of saffron
      extract was seen in both cell lines. At a concentration of 800 microg/mL, the
      survived L929 cells plummeted to less than 60% after 120 hours, while no TCC
      cells survived at this time. No L929 cells survived at 2000 microg/mL.
      CONCLUSION: Saffron aqueous extract has inhibitory effects on the growth of both
      TCC 5637 and normal L929 cell lines. This effect is dose dependent.

PMID- 18825623
TI  - Donor nephrectomy with and without preservation of gonadal vein while dissecting
      the ureter.
AB  - INTRODUCTION: Preservation of the gonadal vein while dissecting the ureter for
      donor nephrectomy may decrease the distal ureteral ischemia and urological
      complications in kidney transplant recipients. In this study, we compared the
      outcome of kidney allografts harvested with preservation of the gonadal vein
      while dissecting the ureter with allografts harvested without preserving the
      gonadal vein. MATERIALS AND METHODS: We reviewed 167 consecutive kidney
      transplantations between April 2003 and April 2004. During donor nephrectomy, we
      preserved the gonadal vein in 106 harvested kidneys (group 1), while we did not
      preserve this vein in 61 allografts (group 2). The recipients in each group were
      followed up for a 2-year follow-up on average, and the outcomes including
      ureteral complications, graft loss, and patient and graft survival were compared
      between the two groups. RESULTS: Urine leakage was noted in few patients (2 in
      group 1 and 3 in group 2) and its frequency was not significantly different
      between the two groups (P = .26). Ureteral stricture was not seen in any of the
      kidney allograft recipients. No differences were found in the frequencies of
      acute rejection episodes, graft loss, and death between the two groups.
      CONCLUSION: Preservation of the gonadal veins did not significantly decrease the
      frequency of ureteral complications in the kidney transplant recipients. We
      recommend meticulous handling of the ureter in donor nephrectomies to prevent
      further remote complications regardless of the approach to the gonadal veins
      while nephrectomy.

PMID- 18825624
TI  - Influence of hypernatremia and polyuria of brain-dead donors before organ
      procurement on kidney allograft function.
AB  - INTRODUCTION: Polyuria and hypernatremia are common problems during the
      pretransplant care of brain-dead donors. They have not only important role in
      hemodynamic stability, but also may influence organ transplantation outcomes. The
      influence of donor hypernatremia in liver transplantation was reported. This
      study aimed to determine these effects on kidney allograft. MATERIALS AND
      METHODS: We retrospectively studied on 57 transplanted kidney allografts from
      cadaveric donors. The effects of the urine output volume and serum level of
      sodium of the donors were on the recipients' serum creatinine levels 1 week after
      transplantation and at the last follow-up visit were assessed. RESULTS: Of the
      donors, 58% had polyuria and 45% had hypernatremia. The median pretransplant
      urine output of the donors was 130 mL/h (range, 35 mL/h to 450 mL/h), and their
      mean serum sodium level was 152.0 +/- 13.0 mEq/L. Serum creatinine concentrations
      in the recipients at the 1st posttransplant week correlated significantly with
      the recipients' age (r = 0.355, P = .02) and the donors' urine output volume (r =
      0.329, P = .04). The serum creatinine measured in the last follow-up visit
      significantly correlated only with the donors' serum sodium levels (r = 0.316, P
      = .02) and the donors' age (r = 0.306, P = .02). Multivariate regression analysis
      showed that the donors' serum levels of sodium and potassium were the predictors
      of the last measured serum creatinine level. CONCLUSION: Polyuria and
      hypernatremia in brain-dead donors are frequent. Elevated serum level of sodium
      and polyuria in the donor can have adverse effects on kidney allograft function.

PMID- 18825625
TI  - Patient and graft survival of kidney allograft recipients with minimal hepatitis
      C virus infection: a case-control study.
AB  - INTRODUCTION: The impact of pretransplant hepatitis C virus (HCV) infection on
      the outcome of kidney transplantation is controversial. This study was designed
      to determine the impact of pretransplant minimal HCV infection on the patient and
      graft survival at a single center in southwest of Iran. MATERIALS AND METHODS: We
      designed a historical cohort study on 337 kidney transplant recipients and
      selected 35 patients with HCV infection and a histological activity index score
      less than 4 (minimal HCV infection). A group of kidney recipients with negative
      anti-HCV antibody were compared with the anti-HCV-positive patients in terms of
      acute allograft rejection, graft loss, mortality, causes of death, and patient
      and graft survival. The controls were matched for age, sex, donor source,
      pretransplant dialysis duration, and panel reactive antibodies test. All of the
      participants had a follow-up period of at least 5 years. RESULTS: There were no
      significant differences in terms of early and late acute allograft rejection
      episodes between the groups. Although patient and graft survival rates were lower
      in HCV-positive patients at 2 and 5 years, the differences between the two groups
      were not significant. The main causes of death among patients with and without
      HCV infection were sepsis and cardiovascular events, respectively. CONCLUSION:
      Our findings suggest that pretransplant minimal HCV infection had no detrimental
      effect on the short-term patient and graft survival. However, we suggest that
      kidney transplant recipients with minimal HCV infection be monitored for severe
      systemic bacterial infections.

PMID- 18825626
TI  - Internal urethrotomy combined with antegrade flexible cystoscopy for management
      of obliterative urethral stricture.
AB  - INTRODUCTION: We studied the safety and efficacy of flexible cystoscopy-guided
      internal urethrotomy in the management of obliterative urethral strictures.
      MATERIALS AND METHODS: Forty-three flexible cystoscopy-guided internal
      urethrotomies were performed between 1999 and 2005. The indication for the
      procedure was nearly blinded bulbar or membranous urethral strictures not longer
      than 1 cm that would not allow passage of guide wire. Candidates were those who
      refused or were unable to undergo urtheroplasty. By monitoring any impression of
      the urethrotome on the monitor through the flexible cystoscope, we were able to
      do under-vision urethrotomy. All of the patients were started clean intermittent
      catheterization afterwards which was tapered over the following 6 months. Follow
      up continued for 24 months after the last internal urethrotomy. RESULTS:
      Seventeen patients were younger than 65 years with a history of failed posterior
      urethroplasty, and 26 were older than 65 with poor cardiopulmonary conditions who
      had bulbar urethral stricture following straddle or iatrogenic injuries. Urethral
      stricture stabilized in 16 patients (37.2%) with a single session of urethrotomy
      and in 17 (39.5%) with 2 urethrotomies. Overall, urethral stricture stabilized in
      76.7% of patients with 1 or 2 internal urethrotomies within 24 months of follow
      up. No severe complication was reported. CONCLUSION: Flexible cystoscopy-guided
      internal urethrotomy is a simple, safe, and under-vision procedure in
      obliterative urethral strictures shorter than 1 cm. It can be an ideal option for
      patients who do not accept posterior urethroplasty or are in a poor
      cardiopulmonary condition that precludes general anesthesia.

PMID- 18825627
TI  - Percutaneous management of urinary calculi in horseshoe kidneys.
AB  - Urolithiasis in horseshoe kidney presents a unique challenge in decision-making
      and technical aspects of calculus treatment. We present our experience with a
      group of patients with symptomatic calculi in their horseshoe kidneys. We had 8
      patients with 9 horseshoe kidneys bearing calculi. They all underwent
      percutaneous nephrolithotomy. The median size of the calculi was 21 mm (range, 12
      to 45 mm). Auxiliary therapeutic procedures were required in 2 patients who had
      residual calculi on control imaging. The stone-free status was observed in 6
      patients (75.0%) at discharge, and in 7 (87.5%) after 3 months of follow-up.
      Surgical complications included bleeding in 2 patients that was controlled with
      complete bed rest and blood transfusion, and pleural injury in 1 which was
      managed conservatively.

PMID- 18825628
TI  - Synchronous bilateral laparoscopic radical nephrectomy for solid renal masses
      using a hybrid approach.

PMID- 18825629
TI  - Mucinous cystadenoma arising from renal pelvis: a report of 2 cases.

PMID- 18825630
TI  - High-grade vesicoureteral reflux in Pfeiffer syndrome.

PMID- 18825631
TI  - Radical retropubic prostatectomy as a solo therapy for treatment of adult
      rhabdomyosarcoma.

PMID- 18825632
TI  - Spermatocele presenting as acute scrotum.

PMID- 18825633
TI  - Re: Overexpression of BMI1, a polycomb group repressor protein, in bladder
      tumors: a preliminary report.

PMID- 18825634
TI  - Re: Laparoscopic distal ureterectomy and Boari flap ureteroneocystostomy for a
      low-grade distal ureteral tumor.

PMID- 18825635
TI  - What's up in Urology Journal, Summer 2008? Urology for People.

PMID- 18825637
TI  - Understanding behavior: animal behavior and animal welfare.

PMID- 18825638
TI  - Dirofilaria immitis in cats: anatomy of a disease.
AB  - It is now understood that wherever heartworm infection exists in the local canine
      population, it will also be found in the feline population. However, this does
      not mean that the parasite and resulting disease behave the same way in both
      species. For example, heartworms rarely reach the adult stage in cats, but they
      can cause respiratory sequelae nonetheless.

PMID- 18825639
TI  - Dirofilaria immitis in cats: diagnosis and management.
AB  - Imaging and laboratory studies can help with the diagnosis of heartworm disease
      in cats, but no test is definitive. Furthermore, even when the diagnosis can be
      reliably established, therapy directed at the heartworms does little to help the
      cat. Rather, management is directed at alleviating clinical signs, with an
      emphasis on prevention for all.

PMID- 18825640
TI  - Hepatitis C virus infection and post-transplant diabetes mellitus among renal
      transplant patients: a meta-analysis.
AB  - OBJECTIVE: To examine the association between HCV infection and the occurrence of
      post-transplant diabetes mellitus (PTDM) among renal transplant patients. DESIGN:
      Meta-analysis of observational studies. DATA SOURCES: We retrieved studies
      published in any language by systematically searching Medline, and Embase and by
      manually examining the references of the original articles, reviews, and
      monographs retrieved. REVIEW METHODS: We included cohort and case-control studies
      reporting relative risk estimates and 95% confidence intervals (CIs) for PTDM
      occurrence with HCV after renal transplantation. Thirteen studies providing
      information on a total of 30,099 unique patients were included in our meta
      analysis. RESULTS: Study-specific relative risks were weighted by the inverse of
      their variance to obtain fixed and a 95% confidence interval (CI) of 1.94; 3.83
      (10 studies). In a stratified analysis including only large studies (2 studies),
      the pooled RR was 1.36 (95% CI, 1.21; 1.54). Egger's regression test showed some
      evidence of publication bias (p=0.0001), but our sensitivity analysis showed that
      this issue did not meaningfully change the results. CONCLUSIONS: Our study shows
      a marked increase of the risk of post-transplant diabetes mellitus in anti
      hepatitis C virus-positive renal transplant recipients. The excess risk of death
      in hepatitis C virus-positive renal transplant recipients may be at least
      partially attributed to post-transplant diabetes mellitus with its attendant
      complications.

PMID- 18825641
TI  - The management of viral hepatitis in CKD patients: an unresolved problem.
AB  - Chronic kidney disease (CKD) patients in dialysis (HD) show peculiar, atypical
      features of clinical presentation and diseases (cardiovascular, metabolic,
      hematologic). This is also true for viral hepatitis infections, for which CKD
      patients represent an important risk group. In the past, hepatitis B virus (HBV)
      was the major cause of viral hepatitis in end-stage renal disease (ESRD).
      However, the introduction of a rigorous infection-control strategy, routine
      screening of patients and staff for hepatitis B serologic markers, vaccination of
      susceptible patients and staff, use of separate rooms and dedicated machines for
      HD of HbsAg-positive patients have all led to a decline in the spread of HBV
      infection in dialysis. Despite the prevalence of the antibody-hepatitis C virus
      (HCV), there has been a marked decrease in HD patients; after the introduction of
      routine screening for HCV and the use of erythropoietin, its occurrence ranges
      from 5% to 25% in the United States, with a prevalence of 6.8% in Europe. In CKD
      and in HD patients, the presence of HBV and HCV is an independent and significant
      risk factor for death and this risk may be at least partially attributed to
      chronic liver disease with its attendant complications. Liver disease can
      progress with modest hepatic inflammation and prominent fibrosis; the natural
      history of viral hepatitis in these patients is dependent on the immune
      dysfunction typical of kidney disease. Despite recent advances in antiviral
      therapy, there are still many uncertainties in regards to the efficacy and long
      term outcomes of treatment with antiviral agents.

PMID- 18825642
TI  - Design, fabrication, and characterization of a composite scaffold for bone tissue
      engineering.
AB  - Poly(lactide-co-glycolide) (PLGA) scaffolds have been successfully used in bone
      tissue engineering, with or without hydroxyapatite (HA) and with a macroporosity
      given either by simple PLGA sphere packaging and/or by leaching out NaCl. The
      objective of this work was the optimization of the design parameters for bone
      tissue engineering scaffolds made by sintering microspheres of PLGA, HA
      nanocrystals for matrix reinforcement and osteoconduction, and salt crystals for
      macroporosity and control of matrix pore size. Microsphere fabrication by a
      single-emulsion and solvent evaporation technique was first optimized to obtain a
      high yield of PLGA microspheres with a diameter between 80 and 300 microm. The
      influence of the sintering process and matrix composition on the scaffold
      structure was then evaluated morphologically and mechanically. Three scaffold
      types were tested for biocompatibility by culturing with human fibroblasts for up
      to 14 days. The most important parameters to obtain microspheres with the
      selected diameter range were the viscosity ratio of the dispersed phase to the
      continuous phase and the relative volume fraction of the 2 phases. The Young's
      modulus and the ultimate strength of the sintered matrices ranged between 168-265
      MPa and 6-17 MPa, respectively, within the range for trabecular bone.
      Biocompatibility was demonstrated by fibroblast adhesion, proliferation, and
      spreading throughout the matrix. This work builds upon previous work of the
      PLGA/HA sintering technique to give design criteria for fabricating a bone tissue
      engineered matrix with optimized morphological, functional, and biological
      properties to fit the requirements of bone replacements.

PMID- 18825643
TI  - Enhancement of osteogenesis by concanavalin A in human bone marrow mesenchymal
      stem cell cultures.
AB  - This study investigates concanavalin A (ConA) as a novel factor that may enhance
      osteogenesis of mesenchymal stem cells (MSCs) in vitro. Various factors, such as
      cytokine bone morphogenetic protein-2 (BMP-2), have been studied for their
      possible promotion of MSC osteogenesis in vivo and in vitro. However, the factor
      that might be safer, more effective, and less expensive than these has not been
      determined. We therefore cultured human MSCs in osteogenic medium in the presence
      or absence of ConA, and used calcium assays to compare the effects of ConA and
      BMP-2 on MSC calcification. We also used enzyme-linked immunosorbent assay
      (ELISA) and quantitative polymerase chain reaction (PCR) to evaluate the
      expression levels of bone-specific markers. ConA and BMP-2 enhanced calcification
      with comparable effectiveness. The combination of ConA and BMP-2 further enhanced
      calcification slightly but significantly. ConA also increased osteocalcin and BMP
      2 protein levels in MSC culture medium. Furthermore, ConA increased osteocalcin,
      RUNX2, BMP-2, BMP-4, and BMP-6 mRNA expression levels. However, the gene
      expression pattern of ConA-stimulated MSCs was different from that of MSCs
      stimulated by BMP-2. Together, these results suggest that ConA and BMP-2 enhance
      MSC osteogenesis via different pathways. ConA-induced bone formation in MSC
      cultures may be useful in regenerative medicine or tissue engineering in clinical
      studies, as well as in basic research on bone formation.

PMID- 18825644
TI  - Improvement of monocyte secretion function in a porcine pancreatitis model by
      continuous dose dependent veno-venous hemofiltration.
AB  - OBJECTIVE: Monocyte and its secreted cytokines play a crucial role in the process
      of severe acute pancreatitis (SAP). It has been known that continuous veno-venous
      hemofiltration (CVVH) can partially attenuate the inflammatory process by removal
      of cytokines, but the effect of CVVH on monocyte secretion function remains
      unknown. This study investigated the effect of different doses of CVVH on
      monocyte secretion function as well as the plasma cytokine profile in a SAP
      porcine model. METHODS: After successful induction of SAP by pressure-controlled
      (100 mmHg), intraductal injection of sodium taurocholate (4%, 1 ml/kg) and
      trypsin (2 U/kg), 24 swine were randomly assigned to 3 groups. Swine in group I
      (n=8) serving as SAP controls received only standard medical therapy (SMT).
      Besides SMT, swine in two other groups received zero-balanced CVVH, one hour
      after the induction of SAP, with low volume fluid exchange (group II, n=8,
      ultrafiltration rate (UFR) 20 ml/kg/h, LV-CVVH) or high volume (group III, n=8,
      UFR 100 ml/kg/h, HV-CVVH). Using heparin as anticoagulant, the filter (AN69,
      Hospal, Lyon, France) was changed every 24 hours. Monocytes were isolated from
      porcine blood at various timepoints for detection of cytokine secretion
      (interleukin-6, IL-6; interleukin-10, IL-10; tumor necrosis-a, TNF-a) after LPS
      stimulus; plasma cytokines were measured simultaneously. RESULTS: CVVH showed a
      dose-dependent beneficial effect on the animals' survival time. In control
      animals, plasma pro-inflammatory cytokine levels exhibited a double-phase
      fluctuation after SAP induction: IL-6 and TNF-alfa rapidly increased to a peak
      level within 6-12 hours, then dropped to very low level in the late stage. Unlike
      pro-inflammatory cytokines, the plasma level of anti-inflammatory cytokine IL-10
      reached a plateau within 6-12 hours but dropped little. In CVVH-treated animals,
      the peak-nadir patterns of 3 cytokines were all flattened, most prominently in
      the HV-CVVH group. Similarly to plasma cytokine patterns, the monocyte ex vivo
      response to LPS stimulus showed an over-production of cytokines within 6-12
      hours, but low production in the late stage. Although unable to totally prevent
      the abnormality of the monocyte secretion function, CVVH showed a dose-dependent
      ameliorative effect on it. CONCLUSIONS: Monocytes are over-reactive to stimulus
      in the early stage of SAP, accompanied by a high level of plasma cytokines, and
      hypo-reactive to stimulus in the late stage of SAP, accompanied with a low level
      of plasma cytokines. CVVH treatment has a dose-dependent improvement effect on
      monocyte responsiveness.

PMID- 18825645
TI  - The effect of three different miniaturized blood purification devices on plasma
      cytokine concentration in an ex vivo model of endotoxinemia.
AB  - PURPOSE: A novel type of adsorptive plasma filtering device (ETX-A) capable of
      removing endotoxin from blood in a single step has recently been developed using
      nanotechnology. METHODS: In a miniaturized, ex vivo model of extracorporeal
      circuits, we tested the capacity to reduce plasma cytokine concentration of ETX-A
      filters in comparison to standard high-flux (HF) filters, high cut-off (HCO)
      filters and a control. Blood from six healthy volunteers was spiked with
      endotoxin and then circulated through closed (ETX-A, control) or open (HF, HCO)
      circuits. Blood flow was set at 16 ml/min and filtration flow at 1 ml/min.
      Samples for measurement of IL-1ra and IL-6 were taken at baseline and at 4 hours.
      RESULTS: Compared to control (703.3 [850.6] pg/mL), in HCO (383.5 [1144.1] pg/mL)
      and ETX-A (490.1 [683.2] pg/mL) filters, plasma IL-1ra pooled pre- and postfilter
      concentrations were lower at the end of the experiment (P=0.002; P=0.050,
      respectively) whereas, in standard HF filters, IL-1ra concentration was higher
      than control. HCO showed a trend toward a reduced relative increase in IL-6
      concentration from commencement to end of experiment compared to control
      (P=0.07). After pooling end-of-experiment plasma cytokine values of novel blood
      purification devices, we found HCO + ETX-A superior to H with regard to reduction
      of IL-1ra (-27.0 [-20.5]% vs. 8.1 [18.9]%; p<0.001) and IL-6 (-18.0 [38.3]% vs. 
      1.1 [24.3]%; P=0.050) compared to control. CONCLUSIONS: HCO and ETX-A appeared to
      significantly reduce plasma IL-1ra and, when combined, plasma IL-6 concentration
      as well. It appears desirable to manufacture full-size blood purification devices
      using this technology and to explore their effect on cytokine removal.

PMID- 18825646
TI  - Monitoring chronic hemodialysis patients: a questionnaire-based survey.
AB  - BACKGROUND: The monitoring program for patients on regular hemodialysis treatment
      (RDT) is not well defined yet by current international guidelines (CIG). METHODS:
      To evaluate the extent to which CIG are implemented, we sent a questionnaire to
      100 Italian hemodialysis units (DU) with questions concerning: (a) the frequency
      with which routine tests were performed for the follow-up of patients on RDT; (b)
      which other non-routine tests were performed. We analyzed the response data and
      compared them with the CIG. RESULTS: We received 37 replies. We found several
      differences between the monitoring program of our respondents and the CIG.
      CONCLUSION: Because of the small number of responses, this survey is only
      preliminary; however, it shows the difficulty nephrologists have in using the CIG
      to create a correct monitoring program in patients on RDT. Although our analysis
      is limited to 37 DUs, it suggests that specific guidelines are necessary to
      optimize the management of patients on RDT.

PMID- 18825647
TI  - Five-year survival in comparable HD and PD patients: one center's experience.
AB  - Several studies have yielded conflicting results regarding morbidity and
      mortality in peritoneal dialysis (PD) and hemodialysis (HD) patients. We
      performed a retrospective analysis in end-stage renal disease (ESRD) patients in
      our department, who were equally distributed between HD and PD, in order to
      compare 5-year survival probabilities and hospitalization rates in the two
      modalities. Of the total 94 new ESRD patients who initiated dialysis in our
      department from January 1995 to December 2000, 48 were allocated to PD and 46 to
      HD. All patients were followed up for five years. There were no significant
      differences regarding demographics and serious co-morbidities upon dialysis
      initiation between HD and PD patients. Unadjusted 5-year survival probability in
      as-treated analysis was higher in PD patients (0.79 vs 0.6, p=0.04), whereas
      there was no significant difference in intent-to-treat analysis between HD and PD
      patients (p=0.5). Hospitalization rates were similar in both modalities. Despite
      the small number of patients included in our study, it seems that when HD and PD
      are both available in one department they have equivalent results regarding
      morbidity and mortality rates. Therefore we suggest that, when possible, PD and
      HD should be equally offered to all ESRD patients.

PMID- 18825648
TI  - Combination of sodium thiosulphate, cinacalcet, and paricalcitol in the treatment
      of calciphylaxis with hyperparathyroidism.
AB  - Calciphylaxis (calcific uremic arteriolopathy) is a severe complication of
      hemodialysis characterized by subcutaneous calcification of the small arteries
      and tissue necrosis. Our case report is focused on a woman receiving hemodialysis
      (HD) with diabetes mellitus for 20 years and severe secondary
      hyperparathyroidism, who presented painful subcutaneous nodules, skin necrosis
      and ulcerations. As the treatment of calciphylaxis is mainly empirical and
      controversial, we decided to administer cinacalcet with paricalcitol for the
      control of hyperparathyroidism and sodium thiosulfate to improve the
      calcification of the arterioles. Two months after the start of the therapy,
      parathyroid hormone (PTH) decreased significantly and the skin lesions nearly
      disappeared. Thus, we believe that the combination of sodium thiosulfate with
      cinacalcet and paracalcitol is effective for the treatment of calciphylaxis with
      secondary hyperparathyroidism.

PMID- 18825649
TI  - Epidemiology of hepatitis C virus infection in hemodialysis patients of Sicily.

PMID- 18825650
TI  - Biomarker discovery using targeted maximum-likelihood estimation: application to
      the treatment of antiretroviral-resistant HIV infection.
AB  - Researchers in clinical science and bioinformatics frequently aim to learn which
      of a set of candidate biomarkers is important in determining a given outcome, and
      to rank the contributions of the candidates accordingly. This article introduces
      a new approach to research questions of this type, based on targeted maximum
      likelihood estimation of variable importance measures.The methodology is
      illustrated using an example drawn from the treatment of HIV infection.
      Specifically, given a list of candidate mutations in the protease enzyme of HIV,
      we aim to discover mutations that reduce clinical virologic response to
      antiretroviral regimens containing the protease inhibitor lopinavir. In the
      context of this data example, the article reviews the motivation for covariate
      adjustment in the biomarker discovery process. A standard maximum-likelihood
      approach to this adjustment is compared with the targeted approach introduced
      here. Implementation of targeted maximum-likelihood estimation in the context of
      biomarker discovery is discussed, and the advantages of this approach are
      highlighted. Results of applying targeted maximum-likelihood estimation to
      identify lopinavir resistance mutations are presented and compared with results
      based on unadjusted mutation-outcome associations as well as results of a
      standard maximum-likelihood approach to adjustment.The subset of mutations
      identified by targeted maximum likelihood as significant contributors to
      lopinavir resistance is found to be in better agreement with the current
      understanding of HIV antiretroviral resistance than the corresponding subsets
      identified by the other two approaches. This finding suggests that targeted
      estimation of variable importance represents a promising approach to biomarker
      discovery.

PMID- 18825651
TI  - A bivariate autoregressive linear mixed effects model for the analysis of
      longitudinal data.
AB  - In clinical studies, dependent bivariate continuous responses may approach
      equilibrium over time. We propose an autoregressive linear mixed effects model
      for bivariate longitudinal data in which the current responses are regressed on
      the previous responses of both variables, fixed effects, and random effects. The
      equilibria are modeled using fixed and random effects. This model is a bivariate
      extension of the model for univariate longitudinal data given by Funatogawa et
      al. (Statist. Med. 2007; 26:2113-2130). As an illustration of the approach we
      analyze parathyroid hormone and serum calcium measurements in the treatment of
      secondary hyperparathyroidism in chronic hemodialysis patients.

PMID- 18825652
TI  - Joint modelling of longitudinal and competing risks data.
AB  - Available methods for joint modelling of longitudinal and survival data typically
      have only one failure type for the time to event outcome. We extend the
      methodology to allow for competing risks data. We fit a cause-specific hazards
      sub-model to allow for competing risks, with a separate latent association
      between longitudinal measurements and each cause of failure.The method is applied
      to data from the SANAD trial of anti-epileptic drugs (AEDs), as a means of
      investigating the effect of drug titration on the relative effects of lamotrigine
      (LTG) and carbamazepine (CBZ) on treatment failure. Concern had been expressed
      that differential titration rates may have been to the disadvantage of CBZ. The
      beneficial effect of LTG on unacceptable adverse events leading to drug
      withdrawal did not lessen and indeed increased slightly when a calibrated dose
      was accounted for in the joint model. Adjustment for the titration rate of LTG
      relative to CBZ resulted in an unchanged effect of the former on drug withdrawals
      due to inadequate seizure control. LTG remains the AED of choice from this
      analysis.

PMID- 18825653
TI  - Modeling the association of bivariate interval-censored data using the copula
      approach.
AB  - In a survival study, it may not be possible to record the exact event time but
      only that the event has occurred between two time points or still has to occur,
      leading to interval-censored survival times.Recently, Sun et al. (Scand. J. Stat.
      2006; 33(4):637-649) suggested to fit a Clayton copula with nonparametric
      marginal distributions to estimate the association for bivariate interval
      censored failure data. We propose here to model the marginal distributions with
      an accelerated failure time model with a flexible error term as suggested by
      Komarek et al. (J. Comput. Graph. Stat. 2005; 14(3):726-745) in combination with
      a one parameter copula. In addition, we allow the association parameter of the
      copula to depend on covariates.The performance of our method is illustrated by an
      extensive simulation study and is applied to tooth emergence data of permanent
      teeth measured on 4468 children from a longitudinal dental study.

PMID- 18825654
TI  - Comments on 'How conservative is Fisher's exact test? A quantitative evaluation
      of the two-sample comparative binomial trial' by G. G. Crans and J. J. Shuster,
      Statistics in Medicine 2008; 27:3598-3611.

PMID- 18825655
TI  - Strategies for analyzing multilevel cluster-randomized studies with binary
      outcomes collected at varying intervals of time.
AB  - Frequently, studies are conducted in a real clinic setting. When the outcome of
      interest is collected longitudinally over a specified period of time, this design
      can lead to unequally spaced intervals and varying numbers of assessments. In our
      study, these features were embedded in a randomized, factorial design in which
      interventions to improve blood pressure control were delivered to both patients
      and providers. We examine the effect of the intervention and compare methods of
      estimation of both fixed effects and variance components in the multilevel
      generalized linear mixed model. Methods of comparison include penalized quasi
      likelihood (PQL), adaptive quadrature, and Bayesian Monte Carlo methods. We also
      investigate the implications of reducing the data and analysis to baseline and
      final measurements. In the full analysis, the PQL fixed-effects estimates were
      closest to zero and confidence intervals were generally narrower than those of
      the other methods. The adaptive quadrature and Bayesian fixed-effects estimates
      were similar, but the Bayesian credible intervals were consistently wider.
      Variance component estimation was markedly different across methods, particularly
      for the patient-level random effects. In the baseline and final measurement
      analysis, we found that estimates and corresponding confidence intervals for the
      adaptive quadrature and Bayesian methods were very similar. However, the time
      effect was diminished and other factors also failed to reach statistical
      significance, most likely due to decreased power. When analyzing data from this
      type of design, we recommend using either adaptive quadrature or Bayesian methods
      to fit a multilevel generalized linear mixed model including all available
      measurements.

PMID- 18825656
TI  - Analysis of carbohydrates and glycoconjugates by matrix-assisted laser
      desorption/ionization mass spectrometry: An update for 2003-2004.
AB  - This review is the third update of the original review, published in 1999, on the
      application of matrix-assisted laser desorption/ionization (MALDI) mass
      spectrometry to the analysis of carbohydrates and glycoconjugates and brings the
      topic to the end of 2004. Both fundamental studies and applications are covered.
      The main topics include methodological developments, matrices, fragmentation of
      carbohydrates and applications to large polymeric carbohydrates from plants,
      glycans from glycoproteins and those from various glycolipids. Other topics
      include the use of MALDI MS to study enzymes related to carbohydrate biosynthesis
      and degradation, its use in industrial processes, particularly biopharmaceuticals
      and its use to monitor products of chemical synthesis where glycodendrimers and
      carbohydrate-protein complexes are highlighted.

PMID- 18825657
TI  - A role for interleukin-6 in spreading endothelial cell activation after
      phagocytosis of necrotic trophoblastic material: implications for the
      pathogenesis of pre-eclampsia.
AB  - Pre-eclampsia is characterized by systemic maternal endothelial dysfunction that
      precedes the onset of clinical symptoms. The cause of the dysfunction is not
      clear but the number and the nature of trophoblasts shed from the placenta may be
      altered in pre-eclamptic pregnancies. These dead trophoblasts become trapped in
      the pulmonary capillaries and may then be phagocytosed by endothelial cells.
      Phagocytosis of necrotic, but not apoptotic, trophoblasts results in endothelial
      cell activation. We have explored the hypothesis that activation can subsequently
      spread to other endothelial cells via soluble factors without the need for direct
      contact with shed trophoblasts. Conditioned medium from endothelial cells that
      had phagocytosed necrotic, but not apoptotic, trophoblasts was shown to activate
      fresh endothelial cells due, in large part, to IL-6 secreted into the conditioned
      medium. The amount of IL-6 secreted in response to phagocytosis of necrotic
      trophoblasts was similar to the levels of IL-6 found by others in the blood of
      pre-eclamptic women and was substantially more than the level of IL-6 which has
      been reported to induce symptoms of pre-eclampsia in pregnant rats. We
      demonstrated that phagocytosis of both a trophoblast cell line as well as
      trophoblasts shed from human placentae, had this effect on two different types of
      endothelial cells. The role of IL-6 in endothelial cell activation was confirmed
      using recombinant IL-6 and neutralizing antibodies against IL-6 and the IL-6
      receptor. Thus, IL-6 secreted by pulmonary endothelial cells after they have
      phagocytosed necrotic trophoblasts that are trapped in the pulmonary capillaries
      could activate endothelial cells in other remote vascular beds, contributing to
      the systemic activation of the endothelium that is a hallmark of pre-eclampsia.

PMID- 18825658
TI  - Histopathological and molecular analysis of gastrectomy specimens from hereditary
      diffuse gastric cancer patients has implications for endoscopic surveillance of
      individuals at risk.
AB  - Hereditary diffuse gastric cancer (HDGC) is caused by germline E-cadherin (CDH1)
      mutations in 25-40% of tested families. Management options for asymptomatic
      mutation carriers are fraught, since endoscopic surveillance can miss cancer foci
      and prophylactic gastrectomy has profound clinical sequelae. The aims of this
      study were to evaluate the impact of current surveillance practices on pre
      operative diagnosis and to characterize the microscopic lesions in gastrectomy
      specimens to better inform clinical practice. Histological assessment and mapping
      of endoscopic surveillance and gastrectomy specimens were performed for eight
      asymptomatic CDH1 mutation carriers. E-cadherin expression and proliferation were
      analysed and evidence of epithelial-mesenchymal transition (EMT) was sought by
      immunohistochemistry for vimentin and cytokeratin 8/18. Four of eight patients
      had lesions detected at endoscopic surveillance. A median of 20.5 (range 0-66)
      signet ring foci were identified per gastrectomy (including in situ lesions and
      pagetoid spread). Foci were predominantly identified in the fundus and body (90%
      endoscopic biopsies and 85% in gastrectomy). The likelihood of detecting foci pre
      operatively was positively correlated with the number of biopsies taken and the
      number of lesions in the gastrectomy specimen. E-cadherin expression in
      gastrectomy specimens was reduced or absent in all of the foci compared with the
      intervening gastric tissue, suggesting that these lesions are polyclonal. The
      foci had a low proliferative index (<2%) and there was no evidence for EMT.
      Multiple endoscopic biopsy sampling of the gastric mucosa increases the yield of
      microscopic cancer foci. The low proliferative index and lack of EMT suggests
      that these foci may represent an indolent stage of HDGC.

PMID- 18825659
TI  - Botulinum toxin type A treatment of painful focal neuropathies: new evidence for
      efference of afferents.

PMID- 18825660
TI  - Multiple system atrophy: a primary oligodendrogliopathy.
AB  - To this day, the cause of multiple system atrophy (MSA) remains stubbornly
      enigmatic. A growing body of observations regarding the clinical, morphological,
      and biochemical phenotypes of MSA has been published, but the interested student
      is still left without a clue as to its underlying cause. MSA has long been
      considered a rare cousin of Parkinson's disease and cerebellar degeneration; it
      is rich in acronyms but poor in genetic and environmental leads. Because of the
      worldwide research efforts conducted over the last two decades and the discovery
      of the alpha-synuclein-encoding SNCA gene as a cause of rare familial Parkinson's
      disease, the MSA field has seen advances on three fronts: the identification of
      its principal cellular target, that is, oligodendrocytes; the characterization of
      alpha-synuclein-rich glial cytoplasmic inclusions as a suitable marker at
      autopsy; and improved diagnostic accuracy in living patients resulting from
      detailed clinicopathological studies. The working model of MSA as a primary glial
      disorder was recently strengthened by the finding of dysregulation in the
      metabolism of myelin basic protein and p25alpha, a central nervous system
      specific phosphoprotein (also called tubulin polymerization promoting protein,
      TPPP). Intriguingly, in early cases of MSA, the oligodendrocytic changes in
      myelin basic protein and p25alpha processing were recorded even before formation
      of glial cytoplasmic inclusions became detectable. Here, we review the evolving
      concept that MSA may not just be related to Parkinson's disease but also share
      traits with the family of demyelinating disorders. Although these syndromes vary
      in their respective cause of oligodendrogliopathy, they have in common myelin
      disruption that is often followed by axonal dysfunction.

PMID- 18825661
TI  - Arsenic trioxide and low-dose cytarabine in older patients with untreated acute
      myeloid leukemia, excluding acute promyelocytic leukemia.
AB  - BACKGROUND: Acute myeloid leukemia (AML) carries a dismal prognosis in older
      patients. In this study, the authors evaluated the safety and efficacy of arsenic
      trioxide combined with low-dose cytarabine in untreated patients aged >or=60
      years with AML. METHODS: In a phase 1/2 design, arsenic trioxide was administered
      intravenously at a dose of 0.25 mg/kg on Days 1 through 5 and on Days 8 through
      12, and low-dose cytarabine was given subcutaneously twice daily on Days 1
      through 14 in escalating doses to a target of 10 mg/m(2) per dose. Of 64 patients
      who had pathologically confirmed AML, excluding patients with acute promyelocytic
      leukemia and using World Health Organization criteria, the median age was 71
      years, 10 patients (16%) had treatment-related AML, 40 patients (63%) had an
      antecedent myelodysplastic syndrome or myeloproliferative disorder, and 35
      patients (55%) had unfavorable cytogenetics. Thirty-four patients (53%) had an
      Eastern Cooperative Oncology Group performance status of 2 or 3. RESULTS:
      Complete remission was achieved in 21 of 61 patients (34%), including 15 of 50
      patients (30%) who had secondary or treatment-related AML, 10 of 33 patients
      (30%) who had unfavorable cytogenetics, and 6 of 34 patients (18%) who had a poor
      baseline performance status. The mortality rate within the first 4 weeks was 8%.
      Neutropenic fever was observed in >80% of patients, and 41% of patients had
      bacteremia. Nonhematologic toxicity generally was mild and reversible and
      included fatigue, nausea, diarrhea, rash, peripheral edema, and elevated
      transaminases. There were no clinically significant cardiac arrhythmias.
      CONCLUSIONS: The addition of arsenic trioxide to low-dose cytarabine appeared to
      improve responses in elderly patients who had AML compared with either agent
      alone, and a randomized trial of the combination versus single-agent low-dose
      cytarabine is ongoing.

PMID- 18825662
TI  - Developmental impact of a familial GABAA receptor epilepsy mutation.
AB  - OBJECTIVE: A major goal of epilepsy research is to understand the molecular and
      functional basis of seizure genesis. A human GABA(A) gamma2 gene mutation (R43Q)
      is associated with generalized epilepsy. Introduction of this mutation into a
      mouse by gene targeting recapitulates the human phenotype demonstrating a strong
      genotype to phenotype link. GABA(A) receptors play a role in the moment-to-moment
      control of brain function and also on the long-term wiring of the brain by
      directing neuronal development. Our objective was to determine whether
      developmental expression of the mutation alters seizure susceptibility later in
      life. METHODS: A tetracycline-based conditional model for activation of a
      hypomorphic Q43 disease allele was created and validated. Seizure susceptibility
      was assessed using the subcutaneous pentylenetetrazole model. RESULTS: Seizure
      susceptibility was significantly reduced in mice where the Q43 allele was
      suppressed during development. INTERPRETATION: These results demonstrate that a
      human epilepsy-causing mutation impacts network stability during a critical
      developmental period. These data suggest that identification of presymptomatic
      children may provide a window for therapeutic intervention before overt symptoms
      are observed, potentially altering the course of epileptogenesis.

PMID- 18825664
TI  - Enhanced circadian phase resetting in R192Q Cav2.1 calcium channel migraine mice.
AB  - OBJECTIVE: Mammalian circadian rhythms are driven by the circadian pacemaker of
      the suprachiasmatic nucleus (SCN) and are synchronized to the external 24-hour
      light/dark cycle. After advance time zone transitions (eastbound jet lag), overt
      circadian rhythms require several days to adjust. The retarded adaptation may
      protect against acute imbalance of different brain systems. Abrupt circadian
      rhythm changes may trigger migraine attacks, possibly because migraineurs have an
      inadequate adaptation mechanism. The novel R192Q knock-in migraine mouse model
      carries mutated Ca(v)2.1 calcium channels, causing increased presynaptic calcium
      influx and neurotransmitter release. We investigated whether these mice have an
      abnormal adjustment to phase advance shifts. METHODS: We examined phase resetting
      to 6-hour advance shifts of the light/dark cycle with behavioral and
      electroencephalographic recordings in R192Q and wild-type mice. We recorded
      excitatory postsynaptic currents in the SCN, and electrical impulse frequency in
      vitro and in vivo. RESULTS: R192Q mice showed a more than twofold enhanced
      adjustment of behavioral wheel-running activity and electroencephalographic
      patterns, as well as enhanced shifts of electrical activity of SCN neurons in
      vivo. No differences were found for in vitro recordings of the electrical impulse
      frequency in SCN slices. INTERPRETATION: R192Q migraine mice lack the
      physiological retardation in circadian adaptation to phase advance shifts. The
      opposite findings in vivo and in vitro exclude involvement of the retinal input
      pathway or the phase-shifting capacity of the SCN. Thus, the physiological
      inhibitory process appears to be mediated by Ca(v)2.1 channel-dependent afferent
      signaling from extra-SCN brain areas to the SCN.

PMID- 18825669
TI  - Orphan economics: the downside of supplyside pharmacology.

PMID- 18825663
TI  - The prostaglandin E2 EP2 receptor accelerates disease progression and
      inflammation in a model of amyotrophic lateral sclerosis.
AB  - OBJECTIVE: Inflammation has emerged as an important factor in disease progression
      in human and transgenic models of amyotrophic lateral sclerosis (ALS). Recent
      studies demonstrate that the prostaglandin E(2) EP2 receptor is a major regulator
      of inflammatory oxidative injury in innate immunity. We tested whether EP2
      signaling participated in disease pathogenesis in the G93A superoxide dismutase
      (SOD) model of familial ALS. METHODS: We examined the phenotype of G93A SOD mice
      lacking the EP2 receptor and performed immunocytochemistry, quantitative reverse
      transcriptase polymerase chain reaction, and Western analyses to determine the
      mechanism of EP2 toxicity in this model. RESULTS: EP2 receptor is significantly
      induced in G93A SOD mice in astrocytes and microglia in parallel with increases
      in expression of proinflammatory enzymes and lipid peroxidation. In human ALS,
      EP2 receptor immunoreactivity was upregulated in astrocytes in ventral spinal
      cord. In aging G93A SOD mice, genetic deletion of the prostaglandin E(2)EP2
      receptor improved motor strength and extended survival. Deletion of the EP2
      receptor in G93A SOD mice resulted in significant reductions in levels of
      proinflammatory effectors, including cyclooxygenase-1, cyclooxygenase-2,
      inducible nitric oxide synthase, and components of the NADPH oxidase complex. In
      alternate models of inflammation, including the lipopolysaccharide model of
      innate immunity and the APPSwe-PS1DeltaE9 model of amyloidosis, deletion of EP2
      also reduced expression of proinflammatory genes. INTERPRETATION: These data
      suggest that prostaglandin E(2) signaling via the EP2 receptor functions in the
      mutant SOD model and more broadly in inflammatory neurodegeneration to regulate
      expression of a cassette of proinflammatory genes. Inhibition of EP2 signaling
      may represent a novel strategy to downregulate the inflammatory response in
      neurodegenerative disease.

PMID- 18825670
TI  - Investigator balkanization.

PMID- 18825672
TI  - Is progressive multiple sclerosis a gray matter disease?

PMID- 18825673
TI  - Axonal loss and myelin in early ON loss in postacute optic neuritis.
AB  - OBJECTIVE: To investigate the relation between retinal nerve fiber layer (RNFL)
      thickness and latency and amplitude of multifocal visual-evoked potentials
      (mfVEPs) in the postacute stage of optic neuritis in patients with early or
      possible multiple sclerosis. METHOD: Thirty-two patients with clinical diagnosis
      of unilateral optic neuritis and magnetic resonance imaging lesions typical of
      demyelination and 25 control subjects underwent mfVEP and optical coherence
      tomography imaging. RESULTS: Although there was significant reduction of RNFL
      thickness in the affected eyes (18.7%), a considerably larger decrease was
      observed for the amplitude of the mfVEPs (39.8%). Latency of the mfVEPs was also
      significantly delayed in optic neuritis eyes. In fellow eyes, the amplitude of
      mfVEPs was significantly reduced and the latency prolonged, but RNFL thickness
      remained unaltered. RNFL thickness correlated highly with the mfVEP amplitude (r
      = 0.90). There was also strong correlation between optical coherence tomography
      measure of axonal loss and mfVEP latency (r = -0.66). INTERPRETATION: Although
      our findings demonstrate strong associations between structural and functional
      measures of optic nerve integrity, the functional loss was more marked. This
      fact, together with amplitude and latency changes of the mfVEPs observed in
      clinically normal fellow eyes, may indicate greater sensitivity of mfVEPs in
      detecting optic nerve abnormality or the presence of widespread inflammation in
      the central nervous system, or both. The significant correlation of the mfVEP
      latency with RNFL thickness suggests a role for demyelination in promoting axonal
      loss.

PMID- 18825674
TI  - Autoantibodies in gluten ataxia recognize a novel neuronal transglutaminase.
AB  - OBJECTIVE: Gluten sensitivity typically presents as celiac disease, a chronic,
      autoimmune-mediated, small-intestinal disorder. Neurological disorders occur with
      a frequency of up to 10% in these patients. However, neurological dysfunction can
      also be the sole presenting feature of gluten sensitivity. Development of
      autoimmunity directed toward different members of the transglutaminase gene
      family could offer an explanation for the diversity in manifestations of gluten
      sensitivity. We have identified a novel neuronal transglutaminase isozyme and
      investigated whether this enzyme is the target of the immune response in patients
      with neurological dysfunction. METHODS: Using recombinant human
      transglutaminases, we developed enzyme-linked immunosorbent assays and inhibition
      assays to analyze serum samples of patients with gluten-sensitive
      gastrointestinal and neurological disorders, and various control groups including
      unrelated inherited or immune conditions for the presence and specificity of
      autoantibodies. RESULTS: Whereas the development of anti-transglutaminase 2 IgA
      is linked with gastrointestinal disease, an anti-transglutaminase 6 IgG and IgA
      response is prevalent in gluten ataxia, independent of intestinal involvement.
      Such antibodies are absent in ataxia of defined genetic origin or in healthy
      individuals. Inhibition studies showed that in those patients with ataxia and
      enteropathy, separate antibody populations react with the two different
      transglutaminase isozymes. Furthermore, postmortem analysis of brain tissue
      showed cerebellar IgA deposits that contained transglutaminase 6. INTERPRETATION:
      Antibodies against transglutaminase 6 can serve as a marker in addition to human
      leukocyte antigen type and detection of anti-gliadin and anti-transglutaminase 2
      antibodies to identify a subgroup of patients with gluten sensitivity who may be
      at risk for development of neurological disease.

PMID- 18825676
TI  - Collagen VI glycine mutations: perturbed assembly and a spectrum of clinical
      severity.
AB  - OBJECTIVE: The collagen VI muscular dystrophies, Bethlem myopathy and Ullrich
      congenital muscular dystrophy, form a continuum of clinical phenotypes. Glycine
      mutations in the triple helix have been identified in both Bethlem and Ullrich
      congenital muscular dystrophy, but it is not known why they cause these different
      phenotypes. METHODS: We studied eight new patients who presented with a spectrum
      of clinical severity, screened the three collagen VI messenger RNA for mutations,
      and examined collagen VI biosynthesis and the assembly pathway. RESULTS: All
      eight patients had heterozygous glycine mutations toward the N-terminal end of
      the triple helix. The mutations produced two assembly phenotypes. In the first
      patient group, collagen VI dimers accumulated in the cell but not the medium,
      microfibril formation in the medium was moderately reduced, and the amount of
      collagen VI in the extracellular matrix was not significantly altered. The second
      group had more severe assembly defects: some secreted collagen VI tetramers were
      not disulfide bonded, microfibril formation in the medium was severely
      compromised, and collagen VI in the extracellular matrix was reduced.
      INTERPRETATION: These data indicate that collagen VI glycine mutations impair the
      assembly pathway in different ways and disease severity correlates with the
      assembly abnormality. In mildly affected patients, normal amounts of collagen VI
      were deposited in the fibroblast matrix, whereas in patients with moderate-to
      severe disability, assembly defects led to a reduced collagen VI fibroblast
      matrix. This study thus provides an explanation for how different glycine
      mutations produce a spectrum of clinical severity.

PMID- 18825677
TI  - Etiology and prognosis of fulminant hepatitis in adults.
AB  - 1. Establishing the cause of fulminant hepatitis is an important step in the
      management of acute liver failure, so that specific therapy can be initiated and
      any contraindications to liver transplantation can be eliminated. 2. The etiology
      of fulminant hepatitis varies in different countries and at different times. A
      viral etiology (in particular hepatitis B virus) is now less frequent, and
      paracetamol-induced fulminant hepatic failure is more common. 3. Many patients
      have miscellaneous causes of fulminant hepatitis. It is important to establish
      the main clinical and biological characteristics for specific management. 4.
      Assessment of the prognosis of fulminant hepatitis is important for
      distinguishing patients requiring liver transplantation from those whose will
      improve spontaneously. Prognosis depends on several factors, including the gold
      standard, the King's College Hospital criteria and Clichy's criteria.

PMID- 18825678
TI  - Etiology and prognosis of acute liver failure in children.
AB  - 1. The etiology of acute liver failure in children differs from that in adults,
      with metabolic conditions being commoner in Europe and North America and
      hepatitis A being the commonest cause in Asia and South America. 2.
      Encephalopathy usually is a late feature and is not essential for the diagnosis.
      3. Unlike adults, there are no good prognostic criteria that can predict survival
      without liver transplantation. 4. It is important to exclude genetic multisystem
      disorders before liver transplantation is considered.

PMID- 18825679
TI  - Long-term improvement in health-related quality of life after orthotopic liver
      transplantation.

PMID- 18825680
TI  - Incidence of de novo cancer and lymphoproliferative disorders after liver
      transplantation in relation to age and duration of follow-up.

PMID- 18825681
TI  - Expanded criteria for liver transplantation in patients with cirrhosis and
      hepatocellular carcinoma.
AB  - Orthotopic liver transplantation (OLT) selection for patients with hepatocellular
      carcinoma (HCC) is a matter of debate. The Milan criteria (MC) have been largely
      adopted by the international community. The main aim of this study was to
      evaluate the survival rates and recurrence probabilities of a new proposal for
      criteria (up to 3 tumors, each no larger than 5 cm, and a cumulative tumor burden
      </= 10 cm). Patients with cirrhosis and HCC included on the waiting list (WL)
      from 1991 to 2006 were retrospectively analyzed. Outcomes in patients who had
      tumors within and beyond the MC were compared. The survival analysis was done (1)
      with the intention-to-treat principle and (2) among transplanted patients. A
      total of 281 patients were included in WL. Twenty-four cases did not undergo OLT
      (a dropout rate of 8.5%); all but 1 case had tumors within the MC. Of the 257
      transplanted patients, 26 had tumors beyond the MC in the pre-OLT evaluation.
      Based on the intention-to-treat analysis, the 5-year survival was 56% versus 66%
      in patients who had tumors within and beyond the MC, respectively (P = 0.487).
      Among transplanted patients, the 5-year survival was 62% versus 69%, respectively
      (P = 0.734). Through multivariate analysis, microvascular invasion was an
      independent prognostic factor of poor survival (P = 0.004). The recurrence
      probabilities at 1 and 5 years were 7% versus 12% and 14% versus 28% in patients
      with tumors within and beyond the MC, respectively (P = 0.063). The multivariate
      analysis demonstrated that both poorly differentiated tumors (P < 0.001) and
      microvascular invasion (P < 0.001) increased the risk of recurrence. The
      expansion to up to 3 nodules, each up to 5 cm, and a cumulative tumor burden </=
      10 cm did not result in a reduction of survival in comparison with patients who
      had tumors within the MC.

PMID- 18825682
TI  - Risk factors and outcomes in post-liver transplantation bile duct stones and
      casts: A case-control study.
AB  - Bile duct stones and casts (BDS) after liver transplantation are associated with
      significant morbidity. Risk factors for BDS formation and the efficacy of
      treatment in liver transplant recipients have not been systematically studied.
      The aim of this study was to evaluate potential risk factors for the formation of
      BDS in patients post-liver transplant. A case-control study of consecutive liver
      transplant recipients at a university hospital from 1989 to 2007 was performed to
      identify risk factors for BDS formation. Cases included all liver transplant
      recipients with BDS, excluding those with concurrent t-tubes or biliary stents.
      Controls were chosen randomly from the total liver transplant population matched
      for year of transplantation. Pre- and post-OLT risk factors were analyzed with
      univariate and multivariate analyses. There were 49 cases and 101 controls over
      an 18-year-period (1289 liver transplants performed) with an incidence of 3.8%
      for BDS. In the cases, the median time to BDS diagnosis was 613 days from time of
      transplant. The controls had a median follow-up of 1530 days. Use of
      ursodeoxycholic acid was protective (P = 0.005), whereas bile duct pathology (P =
      0.003), total cholesterol >/= 200 mg/dL (P = 0.008), and triglyceride >/= 150
      mg/dL (P = 0.008) were significant risk factors for BDS formation. Endoscopic
      retrograde cholangiopancreatography (ERCP) was technically successful in all
      cases with resolution or improvement of liver chemistries in 59% (29) of
      patients. In conclusion, significant risk factors for forming BDS included bile
      duct pathology and elevated total cholesterol and triglyceride levels.
      Ursodeoxycholic acid had a significant effect in preventing the development of
      posttransplant BDS and should be used in those that are at increased risk. ERCP
      is a safe and effective diagnostic and therapeutic modality for these patients.

PMID- 18825683
TI  - Biliary cast syndrome following liver transplantation: Predictive factors and
      clinical outcomes.
AB  - Biliary cast syndrome (BCS), the presence of biliary casts and debris causing
      biliary obstruction, occurs in 4%-18% of orthotopic liver transplant (OLT)
      recipients. Potential consequences include cholangitis and graft damage or loss.
      Limited data exist regarding the etiology and outcomes of BCS. The purpose of
      this study was to evaluate donor and recipient risk factors and determine the
      impact of BCS. A retrospective review of 355 OLT cases identified 9 BCS patients
      (2.5%) diagnosed by cholangiography. Twenty-six matched controls were also
      identified. The warm ischemic time was significantly longer in BCS patients.
      Other recipient and donor preoperative and intraoperative characteristics,
      including the donor risk index, revealed no significant differences. Overall
      patient survival showed a trend toward worse outcomes at 6, 12, and 18 months and
      end of follow-up in the BCS group. Overall graft survival was also worse in the
      BCS group at all time periods, with statistical significance demonstrated at 18
      months and end of follow-up. The number of therapeutic biliary procedures and
      hospital readmissions was significantly higher in the BCS group. Twenty-two
      percent of the BCS patients required repeat OLT versus none of the control
      patients. In conclusion, BCS is an uncommon complication of OLT. Except for a
      longer warm ischemic time, recipient and donor factors did not predict the
      occurrence of BCS. BCS patients showed a significantly worse graft survival, as
      well as a trend toward worse patient survival. Given the negative impact of BCS
      on liver transplant outcomes, further studies appear justified.

PMID- 18825684
TI  - Quality of life up to 30 years following liver transplantation.
AB  - Liver transplantation provides a return to a satisfactory quality of life (QOL)
      for the majority of patients in the short to medium term (first 5 years), but
      there is very little information on the QOL in the longer term and the factors
      influencing it. We therefore undertook a single-center cross-sectional analysis
      to determine QOL in patients 10 or more years after liver transplantation. All
      liver transplant recipients who were followed up at the Cambridge Transplant Unit
      for 10 or more years (transplanted between 1968 and 1994) and resident in the
      United Kingdom were asked to complete by post the Short Form 36 version 2 and the
      Ferrans and Powers questionnaires to evaluate their QOL. Univariate and
      multivariate analysis were performed to assess the relationship between a range
      of clinical parameters and QOL. One hundred two patients were invited to
      participate, and 61 (59.8%) responded. Overall, the patients reported a
      satisfactory QOL. On the Ferrans and Powers questionnaire, the patients had a
      mean Quality of Life Index score of 24.5. Factors associated with reduced
      physical functioning were age > 50 years at transplantation, female gender, and
      recurrence of the primary liver disease. On the Short Form 36 version 2
      questionnaire, recipients had reduced physical functioning but normal mental
      health parameters in comparison with the normal population. Age > 60 years at the
      time of survey, female gender, and posttransplant complications were associated
      with reduced physical functioning. In conclusion, patients 10 or more years after
      liver transplantation generally have a good QOL, although physical functioning is
      reduced. Addressing issues such as recurrent disease and posttransplant problems
      such as osteoporosis may help to improve long-term QOL.

PMID- 18825685
TI  - Application of intensive care medicine principles in the management of the acute
      liver failure patient.
AB  - 1. Acute liver failure is a paradigm for multiple system organ failure that
      develops as a consequence of sepsis. 2. In the United States, systemic
      inflammatory response, sepsis, and septic shock are common reasons for intensive
      care unit admission. Intensive care management of these patients serves as a
      template for the management of patients with acute liver failure. 3. Acute liver
      failure is attended by high mortality. Although intensive care results in
      improved survival, the key treatment is liver transplantation. Intensive care
      unit intervention may open a "window of opportunity" and enable successful liver
      transplantation in patients who are too ill at presentation. 4. Intracranial
      hypertension complicates the course for many patients with acute liver failure.
      Initially, intracranial hypertension results from hyperemia, which is cerebral
      edema that reduces cerebral blood flow and eventuates in herniation. The precepts
      of neurocritical care-monitoring cerebral perfusion pressure, cerebral blood
      flow, and cortical activity-with rapid response to hemodynamic abnormalities,
      maintenance of normoxia, euglycemia, control of seizures, therapeutic
      hypothermia, osmotic therapy, and judicious hyperventilation are key to reducing
      mortality attributable to neurologic failure.

PMID- 18825686
TI  - Prevention and management of brain edema in patients with acute liver failure.
AB  - 1. Intracranial pressure is the pressure exerted by the cranial contents on the
      dural envelope and consists of the partial pressures of the brain, blood, and
      cerebrospinal fluid. 2. Severe cases of acute liver failure are frequently
      complicated by brain edema (due to cytotoxic edema) and an increase in cerebral
      blood flow while the cerebrospinal fluid volume remains constant. 3. The
      development of intracranial hypertension in patients with acute liver failure may
      be controlled by manipulation of the position, body temperature, plasma tonicity,
      arterial carbon dioxide tension, and arterial pressure. 4. If intracranial
      hypertension evolves despite these first-tier interventions, increased sedation,
      induction of hypothermia (body temperature of 33 degrees C to 34 degrees C), and
      the use of anti-inflammatory drugs may help secure brain viability.

PMID- 18825687
TI  - Postoperative issues and outcome for acute liver failure.
AB  - 1. Establishing the cause of fulminant hepatitis is an important determinant in
      outcomes after liver transplantation. 2. Liver transplantation is an integral
      part of the management of ALF. 3. In addition to generic posttransplant care,
      neurologic, septic, and hematologic issues need to be addressed. 4. Outcomes
      after liver transplantation are poorer than those for elective transplantation
      but superior to those found for comparably ill patients being transplanted for
      chronic liver disease. 5. Multiple factors have an influence on outcome, and risk
      stratification is beginning to emerge.

PMID- 18825688
TI  - Aortohepatic conduits: a personal commentary.

PMID- 18825689
TI  - Comparative expression of Hedgehog ligands at different stages of prostate
      carcinoma progression.
AB  - Recent studies have revealed the potential involvement of Hedgehog (Hh)
      signalling in proliferation and invasive behaviour of prostate carcinoma (PCa).
      The aim of this study was to specify the role of Sonic Hh (Shh), Desert Hh (Dhh)
      and Indian Hh (Ihh) in the natural history of PCa. Hh ligands expression was
      compared in primary hormone-naive PCa (HNPC), hormone-treated PCa (HTPC) and
      hormone-refractory PCa (HRPC), using immunohistochemistry. Shh and Dhh were
      expressed by both epithelial and stromal cells of prostate tissues. Ihh was only
      expressed by stromal cells. For the three ligands, mRNA and immunostaining were
      not correlated. In HNPC, Shh epithelial expression was significantly associated
      with high Gleason scores (p = 0.03), metastatic lymph nodes (p = 0.004) and Dhh
      epithelial staining was associated with high pT stages (p = 0.003), seminal
      vesicle invasion (p = 0.03) and bladder neck invasion (p = 0.0008). Negative Shh
      staining in stromal cells was associated with high Gleason scores (p = 0.015),
      high pT stages (p = 0.01) and bladder neck invasion (p = 0.04). Concomitant
      absence of Shh and Dhh expression in stromal cells was an independent prognostic
      parameter for biological recurrence on multivariate analysis (p = 0.01).
      Epithelial expression of Shh and Dhh was increased in HTPC compared to HNPC (p =
      0.02 and p = 0.04). Interestingly, in vitro, transcript analysis also showed
      increased expression of these 2 Hh ligands when androgen-sensitive LNCaP cells
      were maintained in androgen-free medium mimicking hormonal therapy. Epithelial
      expression of Dhh was increased (p < 0.0001) in HRPC compared to HNPC, while
      stromal expression of Shh and Dhh was decreased (p < 0.0001). In conclusion, the
      Hh signalling pathway is associated with pejorative pathological parameters in
      HNPC and is up-regulated in epithelial cells of HTPC and HRPC. Moreover, the lack
      of Hh molecules in stromal cells seems to be associated with invasive and hormone
      refractory behaviours and suggests specific changes in stromal-epithelial
      crosstalks during PCa progression.

PMID- 18825690
TI  - Overexpression of TFAP2C in invasive breast cancer correlates with a poorer
      response to anti-hormone therapy and reduced patient survival.
AB  - The AP-2gamma transcription factor encoded by the TFAP2C gene is a member of a
      family of homologous DNA binding proteins that play essential roles during
      vertebrate embryogenesis but show a restricted pattern of expression in the
      adult. Elevated expression of the AP-2alpha and AP-2gamma family members has been
      associated with a number of neoplasms, particularly breast cancer. Here we
      present an exploratory immunohistochemical study of an archival primary breast
      tumour series (n = 75) with parallel clinicopathological data using a new, well
      characterized antibody to AP-2gamma. Heterogeneous, exclusively nuclear
      expression of AP-2gamma was found in the epithelial and myoepithelial
      compartments of normal breast and within tumour epithelial cells. In the breast
      cancer series, the most notable association was a correlation between elevated
      levels of AP-2gamma and shortened patient survival (p = 0.0009*). This
      relationship was also conserved in ER-positive and ErbB2-negative patients; sub
      groups generally considered to have a relatively good prognosis. When patient
      data for survival and duration of treatment response on anti-hormone therapy were
      examined by multivariate analysis, AP-2gamma was revealed in this study to be an
      independent predictor of outcome for both survival (p = 0.005) and response to
      anti-hormone therapy (p = 0.046). Studies using in vitro models confirmed that
      while tamoxifen response is associated with lower levels of AP-2gamma,
      acquisition of resistance to this and other anti-hormone measures (eg faslodex or
      oestrogen deprivation) is associated with high levels of nuclear AP-2gamma.
      Together these data suggest that elevated tumour AP-2gamma expression can
      contribute to the failure of cells to growth arrest following anti-hormone
      treatment and lead to sustained growth and poorer patient outcome.

PMID- 18825691
TI  - Energetic analyses of chair and boat conformations of maleimide substituted
      cyclohexane derivatives.
AB  - An analysis of the conformational preferences of two maleimide substituted
      cyclohexane derivatives proposed as scaffolds for HIV-1 fusion inhibitors is
      presented. Hybrid Low Mode-Monte Carlo (1:1) conformational searches using seven
      different force fields were performed in combination with the GBSA(water) solvent
      model. Low energy structures identified in this way were subjected to geometry
      optimization on the B3LYP/6-31G** surface. Solvent effects were included in the
      quantum calculation using the self-consistent reaction field model for water.
      Quantum results indicate that the 1,3,5-maleimide functionalized 1,3,5-methyl
      cyclohexane is more stable in the boat conformation, whereas 1,3,5-maleimide
      functionalized cyclohexane adopts the expected chair conformation with equatorial
      arms. None of the force fields studied was able to predict the unexpected
      preference for the boat conformation of 1,3,5-maleimide functionalized 1,3,5
      methyl cyclohexane. Comparison of low energy and experimental structures was also
      performed.

PMID- 18825692
TI  - Stability of carbon-centered radicals: effect of functional groups on the
      energetics of addition of molecular oxygen.
AB  - In this paper we examine a series of hydrocarbons with structural features which
      cause a weakening of the C-H bond. We use theoretical calculations to explore
      whether the carbon-centered radicals R(*) which are created after breaking the
      bond can be stabilized enough so that they resist the addition of molecular
      oxygen, i.e. where the reaction R(*) + O(2) --> ROO(*) becomes energetically
      unfavorable. Calculations using a B3LYP-based method provide accurate bond
      dissociation enthalpies (BDEs) for R-H and R-OO(*) bonds, as well as Gibbs free
      energy changes for the addition reaction. The data show strong correlations
      between R-OO(*) and R-H BDEs for a wide variety of structures. They also show an
      equally strong correlation between the R-OO(*) BDE and the unpaired spin density
      at the site of addition. Using these data we examine the major functional group
      categories proposed in several experimental studies, and assess their relative
      importance. Finally, we combine effects to try to optimize resistance to the
      addition of molecular oxygen, an important factor in designing carbon-based
      antioxidants.

PMID- 18825693
TI  - Accurate prediction of thermodynamic properties of alkyl peroxides by combining
      density functional theory calculation with least-square calibration.
AB  - Owing to the significance in kinetic modeling of the oxidation and combustion
      mechanisms of hydrocarbons, a fast and relatively accurate method was developed
      for the prediction of Delta(f)H(298)(o) of alkyl peroxides. By this method, a raw
      Delta(f)H(298)(o) value was calculated from the optimized geometry and vibration
      frequencies at B3LYP/6-31G(d,p) level and then an accurate Delta(f)H(298)(o)
      value was obtained by a least-square procedure. The least-square procedure is a
      six-parameter linear equation and is validated by a leave-one out technique,
      giving a cross-validation squared correlation coefficient q(2) of 0.97 and a
      squared correlation coefficient of 0.98 for the final model. Calculated results
      demonstrated that the least-square calibration leads to a remarkable reduction of
      error and to the accurate Delta(f)H(298)(o) values within the chemical accuracy
      of 8 kJ mol(-1) except (CH(3))(2)CHCH(2)CH(2)CH(2)OOH which has an error of 8.69
      kJ mol(-1). Comparison of the results by CBS-Q, CBS-QB3, G2, and G3 revealed that
      B3LYP/6-31G(d,p) in combination with a least-square calibration is reliable in
      the accurate prediction of the standard enthalpies of formation for alkyl
      peroxides. Standard entropies at 298 K and heat capacities in the temperature
      range of 300-1500 K for alkyl peroxides were also calculated using the rigid
      rotor-harmonic oscillator approximation.

PMID- 18825694
TI  - Human parechovirus causes encephalitis with white matter injury in neonates.
AB  - OBJECTIVE: To assess the role of human parechoviruses (HPeVs) as a cause of
      neonatal cerebral infection and to report neuroimaging findings of newborn
      infants with encephalitis caused by HPeVs. METHODS: Clinical presentation,
      cranial ultrasonography, magnetic resonance imaging (MRI) findings, and
      neurodevelopmental outcome of 10 infants admitted to a neonatal intensive care
      unit and diagnosed with encephalitis caused by HPeVs are reported. RESULTS: Nine
      of 10 infants, with a gestational age of 29 to 41 weeks, presented at 36 to 41
      weeks postmenstrual age with clinical seizures. Seven had a fever and six had a
      rash. Clinical presentation was similar to that of infants with enterovirus
      infection. Cranial ultrasonography showed increased echogenicity in the
      periventricular white matter in all infants. Neonatal MRI confirmed white matter
      changes in nine infants, which changed to gliosis on later MRI. Outcome was
      variable with cerebral palsy in one, a suspect outcome at 18 months in one,
      learning disabilities at 7 years of age in one, epilepsy in one, and normal
      neurodevelopmental outcome in five children. Follow-up of one infant was only 9
      months. INTERPRETATION: HPeVs should be added to the list of neurotropic viruses
      that may cause severe central nervous system infection in the neonatal period.
      White matter injury can be visualized with cranial ultrasonography, but more
      detailed information is obtained with MRI and especially diffusion-weighted
      imaging. Because clinical presentation of HPeV encephalitis is similar to that of
      enterovirus, real-time polymerase chain reaction for both viruses should be
      performed in atypical presentation of neonatal seizures.

PMID- 18825695
TI  - Patient transplant survival not influenced by type of liver graft.

PMID- 18825696
TI  - Role of gender in depressive disorder outcome for individual and group cognitive
      behavioral treatment.
AB  - Gender in cognitive-behavioral therapy (CBT) for outcome for depression has been
      inadequately examined in previous research. Thirty-five men and 55 women
      diagnosed with a depressive disorder according to the Diagnostic and Statistical
      Manual of Mental Disorders, Fourth Edition (DSM-IV; American Psychiatric
      Association, 1994) completed individual CBT at an outpatient community mental
      health clinic and 56 men and 105 women completed group CBT. Depression severity
      was measured before treatment and at endpoint using the Beck Depression Inventory
      II (Beck, Steer, & Brown, 1996) along with secondary outcomes of anxiety (Beck
      Anxiety Inventory; Beck, Epstein, Brown, & Steer, 1988) and quality of life
      (Quality of Life Enjoyment and Satisfaction Questionnaire; Endicott, Nee,
      Harrison, & Blumenthal, 1993). Men and women demonstrated equivalent pretreatment
      and posttreatment illness severity, a comparable gradient of improvement on
      outcomes, and attainment of clinically meaningful benchmarks.

PMID- 18825697
TI  - Hepatitis C therapy before and after liver transplantation.
AB  - 1. Pretransplant therapy, using a low-accelerating-dose regimen, is an option for
      patients with mildly decompensated liver disease and low laboratory Model for End
      Stage Liver Disease scores. Achievement of an on-treatment virologic response is
      the goal of therapy. Preliminary data suggest that up to two-thirds of patients
      who become hepatitis C virus RNA-negative on treatment will be hepatitis C virus
      infection-free post-transplantation. 2. Effective prophylactic therapies are not
      available. Hepatitis C antibody therapy has been ineffective in preventing
      hepatitis C virus infection in studies to date. 3. Preemptive antiviral therapy
      started within weeks of transplantation is limited by tolerability, particularly
      in patients with high Model for End-Stage Liver Disease scores pre
      transplantation. Rates of sustained virologic response vary from 8% to 39%.
      Histological benefits in virologic nonresponders have been demonstrated. 4.
      Posttransplant antiviral therapy in those with evidence of recurrent disease is
      the mainstay of management. A combination of pegylated interferon and ribavirin
      is the treatment of choice, and sustained virologic response is achieved with 48
      weeks of treatment in approximately 30% of treated patients. Attainment of early
      loss of hepatitis C virus RNA is highly predictive of sustained virologic
      response. Histologic improvements are seen in responders. Survival is prolonged
      among those achieving a sustained virologic response. 5. Posttransplant antiviral
      therapy is limited by poor tolerability and the frequent need for dose reductions
      and/or discontinuation. Immunologic complications, including acute rejection,
      chronic rejection, and autoimmune-like hepatitis, occur in association with
      therapy, albeit at low rates. 6. Hepatitis C virus-infected liver transplant
      recipients represent an important patient population in need of new therapeutics
      options to prevent patient and graft losses due to recurrent hepatitis C virus
      disease.

PMID- 18825698
TI  - Vaginal varices with massive hemorrhage in a patient with nonalcoholic
      steatohepatitis and portal hypertension: Successful treatment with liver
      transplantation.

PMID- 18825699
TI  - An unusual cause of lower gastrointestinal bleeding.

PMID- 18825700
TI  - Detection and quantification of (R) and (S)-dechloroethylifosfamide metabolites
      in plasma from children by enantioselective LC/MS/MS.
AB  - Ifosfamide (IF), a potent chemotherapeutic agent for solid tumors, is known to
      cause high rates of nephrotoxicity in children with cancer, which is most likely
      due to the renal production of the metabolite chloroacetaldehyde. Using plasma
      samples obtained from pediatric oncology patients, we developed a simple
      nonderivatizing enantioselective liquid chromatography mass spectrometry method
      to detect the (R) and (S)-2- and 3-dechloroethylifosfamide metabolites. The (R)
      and (S)-enantiomers of the 2- and 3-DCEIF (N-3-dechlroethylifosfamide) were
      detectable in all 22 patients' samples with levels ranging from 9.9 to 238.7
      ng/ml for (R)-2-DCEIF, 15.8 to 663.0 ng/ml for (S)-2-DCEIF, 20.8 to 852.8 ng/l
      for (R)-3-DCEIF and 28.0 to 862.0 ng/ml for (S)-3-DCEIF. In addition, the lower
      limit of quantification for this method is 1 ng/ml. Future studies should
      concentrate on (R) or (S) production of the 2-DCEIF and 3-DCEIF and subsequently
      chloroacetaldehyde formation with the aim of considering the administration of
      only the (R)-IF as its metabolism results in a lower production of
      chloroacetaldehyde.

PMID- 18825702
TI  - Temporary portocaval shunt in orthotopic liver transplantation: need for a
      standardized approach?
AB  - Maintenance of portal and systemic venous return during the anhepatic phase of
      liver transplantation (LT) improves hemodynamic stability. With the piggyback
      technique, caval return is maintained; however, temporary clamping of the portal
      vein is still necessary. The use of a temporary portocaval shunt (TPCS) has been
      proposed to minimize the effect of portal venous interruption. The aim of this
      study was to perform a systematic review of the literature to determine whether
      there is evidence to support the routine use of a TPCS in LT. An electronic
      search of the literature from 1963 to 2007 was performed. A total of 4386
      articles were identified, of which 8 met all the criteria and were included in
      the study. Because of the variability in reporting and the small number of
      studies, statistical comparison was not possible; however, a trend toward a
      shorter operative time, less blood product transfusion, and maintenance of higher
      mean arterial pressures during portal vein clamping was seen in patients with a
      TPCS. In conclusion, the available evidence, albeit scarce, supports the use of a
      TPCS in patients undergoing LT. A prospective randomized study of patients most
      likely to benefit from a TPCS is necessary to substantiate these findings.

PMID- 18825701
TI  - Assessing the toxicity of herbicide isoproturon on Aporrectodea caliginosa
      (Oligochaeta) and its fate in soil ecosystem.
AB  - This study was conducted to determine the residues of isoproturon and its
      metabolites, 1-(4-isopropylphenyl)-3-methylurea, 1-(4-isopropylphenyl) urea, and
      4-isopropylanilin in soil and mature earthworms under laboratory conditions.
      Mature earthworms (Aporrectodea caliginosa) were exposed for various durations
      (7, 15, 30, and 60 days) to soils contaminated with isoproturon concentrations
      (2, 4, 6, 8, and 10 mg kg(-1) soil). The decrease in isoproturon concentration in
      the soil was inversely correlated to it's initial concentration. The highest
      concentration detected for isoproturon in earthworms was observed during the
      first 15 days and decreased thereafter. Acute toxicity of isoproturon was
      investigated; total soluble protein content and glycogen of the worms were
      evaluated. Levels of these parameters were related to isoproturon concentration
      in soil and earthworms. No lethal effect of isoproturon was observed even at the
      concentration of 1200 mg kg(-1) soil after 60 days of exposure. A reduction of
      total soluble protein was observed in all treated worms (maximum 59.54%). This
      study suggests the use of the total soluble protein content and glycogen of
      earthworms as biomarkers of exposure to isoproturon.

PMID- 18825703
TI  - Impact of the hepatitis B virus genotype on pre- and post-liver transplantation
      outcomes.
AB  - Emerging data suggest that the hepatitis B virus (HBV) genotype and the precore
      and core promoter variants impact the outcome of orthotopic liver transplantation
      (OLT) for hepatitis B. The aim of this study was to determine if there is a
      correlation between HBV genotype, precore and core promoter variants, and pre-
      and post-OLT outcomes. Serum samples from patients participating in the National
      Institutes of Health HBV-OLT study were tested for HBV genotype and precore and
      core promoter variants. A total of 123 patients were studied: 43% were Asians,
      46% were Caucasians, and 8% were African Americans. HBV genotypes A (35%) and C
      (35%) were the most prevalent, followed by genotypes D and B. Precore and core
      promoter variants were detectable in 44% and 90% of patients. Patients with
      genotype C were more likely to have hepatocellular carcinoma (HCC) at listing (P
      < 0.001). Waitlist mortality was highest among patients with genotype D, while
      posttransplant mortality was highest among patients with genotype C. Precore or
      core promoter variants did not correlate with pre- or post-OLT survival. In
      conclusion, in this US patient population, patients with genotype C were more
      likely to have HCC at the time of transplant listing and to die after transplant
      than patients with non-C genotypes. Patients with genotype D had the highest
      posttransplant survival, but this was offset by higher waitlist mortality. Our
      study suggests that HBV genotypes but not precore or core promoter variants may
      have an impact on pre- and post-OLT outcomes of hepatitis B patients.

PMID- 18825704
TI  - Risk of malignant neoplasms after liver transplantation: a population-based
      study.
AB  - Posttransplant malignancies have become a serious long-term complication after
      liver transplantation. Our aim was to compare the incidence of posttransplant
      cancers with national cancer incidence rates. The study included all Finnish
      liver transplant patients transplanted at the Helsinki University Central
      Hospital between 1982 and 2005. The cohort was linked with the nationwide Finnish
      Cancer Registry. Observed numbers of cancers were compared to site-specific
      expected numbers based on national cancer incidence rates stratified by age, sex,
      and calendar time. The standardized incidence ratios (SIRs) were calculated as
      observed-to-expected ratios. Thirty-nine posttransplant de novo cancers and 11
      basal cell carcinomas were found in the cohort of 540 patients during 3222 person
      years of follow-up. The overall SIR was 2.59 (95% confidence interval 1.84-3.53).
      SIR was higher for males (SIR 4.16) than for females (SIR 1.74), higher among
      children (SIR 18.1) than among adults (SIR 5.77 for ages of 17-39 years and 2.27
      for ages >/= 40 years), and more elevated in the immediate posttransplant period
      (SIR 3.71 at < 2 years) compared to later periods (SIR 2.46 at 2-10 years and
      1.53 at >10 years). The most common cancer types were nonmelanoma skin cancer
      (SIR 38.5) and non-Hodgkin lymphoma (SIR 13.9). Non-Hodgkin lymphoma was
      associated with male gender, young age, and the immediate posttransplant period,
      whereas old age and antibody induction therapy increased skin cancer risk. In
      conclusion, cancer incidence is increased among liver transplant patients
      compared to the general population. This study points out the importance of
      cancer surveillance after liver transplantation.

PMID- 18825705
TI  - Auxiliary transplantation for acute liver failure: Histopathological study of
      native liver regeneration.
AB  - Auxiliary liver transplantation (ALT) permits the serial assessment of
      regeneration in livers of patients with acute liver failure (ALF). Forty-nine ALF
      patients [32 adults (median age, 23 years; range, 16-40 years) and 17 children
      (median age, 12 years; range, 1-15 years)] underwent ALT between 1994 and 2004 at
      King's College Hospital. Twenty-four patients had seronegative liver failure, 15
      had acetaminophen toxicity, 4 had hepatitis B virus (HBV) infection, 3 had drug
      induced liver failure, 2 had autoimmune hepatitis, and 1 had mushroom poisoning.
      Nine patients without post-ALT native liver histology were excluded from review.
      All acetaminophen-induced, HBV, and drug-related patients had diffuse injury.
      Twelve seronegative patients and the autoimmune hepatitis patient had a map-like
      injury. On follow-up, 9 acetaminophen-induced patients, 9 seronegative patients,
      2 drug-induced ALF patients, 3 HBV patients, and the autoimmune patient recovered
      to a near-normal native liver with inconsequential scarring. The hepatocyte
      proliferative rate in diffuse necrosis was 27.4% (range, 3.1%-69.4%) at
      hepatectomy and sharply decreased after 8 days post-ALT, being minimal months and
      years after ALT. In conclusion, in patients undergoing ALT for ALF with a diffuse
      pattern of liver injury-mainly acetaminophen toxicity-hepatocyte proliferation
      occurs in the native liver within a few days of transplantation. If the injury is
      map-like (most cases of seronegative ALF), regeneration seems to involve variable
      hepatocellular proliferation and potential ductular hepatopoiesis, but sequential
      assessment is difficult because of sampling variation. The likelihood of
      histological recovery appears to be minimal in livers with total hepatocyte loss
      at the time of ALT.

PMID- 18825706
TI  - Abnormal neurological features predict poor survival and should preclude liver
      transplantation in patients with deoxyguanosine kinase deficiency.
AB  - Deoxyguanosine kinase (DGUOK) deficiency is the commonest type of mitochondrial
      DNA depletion associated with a hepatocerebral phenotype. In this article, we
      evaluate predictors of survival and therapeutic options in patients with DGUOK
      deficiency. A systematic search of MEDLINE, LILAC, and SCIELO was carried out to
      identify peer-reviewed clinical trials, randomized controlled trials, meta
      analyses, and other studies with clinical pertinence. DGUOK deficiency was
      searched with the terms dGK, DGUOK, mitochondrial DNA depletion, mtDNA, and
      hepatocerebral. Bibliographies of identified articles were reviewed for
      additional references. Thirteen identified studies met the inclusion criteria and
      were used in this study. The analysis revealed that DGUOK deficiency is
      associated with a variable clinical phenotype. Long-term survival is best
      predicted by the absence of profound hypotonia, significant psychomotor
      retardation, or nystagmus. In the presence of these features, there is increased
      mortality, and liver transplantation does not confer increased survival. In
      summary, liver transplantation appears to be futile in the presence of specific
      neurological signs or symptoms in patients affected with DGUOK deficiency.
      Conversely, in the absence of these neurological features, liver transplantation
      may be considered a potential treatment.

PMID- 18825707
TI  - Twenty years of follow-up of aortohepatic conduits in liver transplantation.
AB  - Arterial problems remain a formidable challenge in liver transplantation. In many
      situations, an aortohepatic conduit can provide a solution. No long-term results
      (over 5 years) have been reported. This study was designed to assess the impact
      of aortohepatic conduits on graft survival after liver transplantation and the
      safety of aortohepatic conduits and to establish the long-term results (up to 20
      years) of aortohepatic conduits. Data from 2346 adult liver transplants were
      prospectively collected into the computerized database and analyzed. In the
      majority of cases, arterial conduits were constructed from the donor iliac artery
      obtained at the liver retrieval. Aortohepatic conduits were required in 149
      (6.4%) first transplants. The long-term graft survival after liver
      transplantation using aortohepatic conduits was excellent and comparable to that
      of the control group. The graft survival was 59% with the conduit versus 67%
      without the conduit at 5 years of follow-up, 50% versus 52% at 10 years, and 33%
      versus 35% at 15 years. With up to 20 years of follow-up, there was no
      statistically significant difference in graft survival, patient survival, hepatic
      artery complications, or biliary complications. For the same time period, there
      was no statistically significant difference in graft survival or patient survival
      for the retransplants with and without aortohepatic conduits. In conclusion, in
      experienced hands, aortohepatic conduits can be used safely for liver
      transplantation with no negative impact on long-term graft survival, patient
      survival, hepatic artery complications, or biliary complications. Excellent long
      term results can be obtained.

PMID- 18825708
TI  - Long-term histological effects of preemptive antiviral therapy in liver
      transplant recipients with hepatitis C virus infection.
AB  - The long-term effects of preemptive antiviral therapy on fibrosis progression in
      liver transplant recipients with hepatitis C virus (HCV) were examined in a
      cohort of consecutive liver transplant recipients who received preemptive
      antiviral therapy for 48 weeks (95% were virologic nonresponders). Control
      patients were transplanted during this same period but did not receive preemptive
      therapy. Patients were followed to the date of last biopsy and censored at the
      time of subsequent HCV treatment. Eighty-six patients surviving >/=90 days were
      included. Treated and control patients were similar, except that treated patients
      had longer histological follow-up (60 versus 50 months), a lower median Model for
      End-Stage Liver Disease score at liver transplant (17 versus 23), and a shorter
      median length of hospital stay (6 versus 9.5 days). In the uncensored analysis,
      the cumulative probability of a Batts-Ludwig fibrosis score >/= 2 at 48 months
      post-liver transplant was 22% in the preemptive therapy group and 49% in the
      nonpreemptive therapy group (P = 0.08). In multivariate analysis, preemptive
      therapy was associated with a 48% reduced risk of a fibrosis score >/= 2 (hazard
      ratio = 0.52, 95% confidence interval = 0.24-1.12, P = 0.09), but this failed to
      achieve statistical significance. Receipt of preemptive therapy was associated
      with a delay in subsequent HCV therapy for moderate to severe disease (fibrosis
      score >/= 2 or moderate necroinflammatory activity) with a median time of 36.3
      months versus 20.3 months in the preemptive and nonpreemptive groups (P = 0.004).
      We conclude that preemptive antiviral therapy in virologic nonresponders delays
      the time to subsequent HCV treatment and may confer a reduced risk of fibrosis
      progression. Further study of preemptive antiviral therapy is warranted.

PMID- 18825709
TI  - Detection and diagnosis of herpes simplex virus infection in adults with acute
      liver failure.
AB  - Disseminated herpes simplex virus (HSV) infection may lead to acute liver failure
      (ALF) and the need for emergency liver transplantation (LT). The primary aim of
      this study was to determine the utility of HSV serological testing and HSV DNA
      testing by polymerase chain reaction (PCR) in the diagnosis and management of
      indeterminate, pregnancy-related, and known HSV-related ALF. Stored sera obtained
      on study day 1 or 2 from patients enrolled in the United States ALF Study Group
      with indeterminate (n = 51), pregnancy-related (n = 12), and HSV-related (n = 4)
      ALF were screened for HSV DNA by PCR and serology. While 7 of the indeterminate
      and pregnant patients had positive anti-HSV immunoglobulin M, none had detectable
      HSV DNA. The 4 known HSV cases all had high-titer HSV DNA on presentation (range:
      3.5 to 36 x 10(8) copies/mL). Two HSV patients underwent LT but developed
      posttransplant extrahepatic HSV infection despite suppression of HSV DNA with
      acyclovir treatment, and one of them eventually died. The 2 other fulminant HSV
      patients died within 48 hours of presentation. In conclusion, serum HSV DNA
      indicative of occult HSV infection was not detected in 51 indeterminate and 12
      pregnancy-related ALF patients. The 4 patients with known HSV-related ALF all had
      high HSV DNA levels at presentation, and despite the rapid use of antiviral
      therapy and emergency LT, substantial morbidity and mortality were encountered,
      highlighting the poor prognosis with severe disseminated HSV infection.

PMID- 18825710
TI  - Early posttransplant hepatic venous outflow obstruction: Long-term efficacy of
      primary stent placement.
AB  - Although balloon angioplasty has been accepted as the safe and effective initial
      treatment to manage hepatic venous outflow abnormalities, it may induce rupture
      of the fresh anastomosis but also may be ineffective to eliminate various
      etiologies of venous outflow abnormalities in the early post-transplant period.
      Therefore, we performed primary stent placement in 108 patients to treat early
      onset (</=4 weeks) post-transplant hepatic venous outflow abnormality. The
      following parameters were documented retrospectively: technical success and
      complications: clinical success; recurrence; and patency of stent-inserted
      hepatic veins.Technical success was achieved in 166 (97.6%) of 170 anastomoses
      (107 patients). Major complications occurred in 5 (4.6%) patients: partial stent
      migration (n = 2) and stent malposition (n = 3). Clinical success was achieved in
      83 (82.2%) of 101 patients who had abnormal liver enzymes or clinical symptoms.
      Seven patients without initial clinical symptoms have remained healthy.
      Restenosis or occlusion of the stent-inserted hepatic veins was documented in 22
      patients at a mean of 9.6 +/- 8.6 months after stent placement. Four of them
      underwent stent replacement or retransplantation due to liver function
      deterioration. Overall 1-, 3-, and 5-year primary patency rates were 82.3 +/-
      0.3%, 75.0 +/- 0.4%, and 72.4 +/- 0.5%, respectively. Multivariate Cox regression
      analysis showed that diameter of stents was an independent factor associated with
      patency of stents (p = 0.001).Primary stent placement seems to be an effective
      treatment modality with an acceptable long-term patency to treat early post
      transplant hepatic venous outflow obstruction.

PMID- 18825711
TI  - Use of the molecular adsorbents recirculating system as a treatment for acute
      decompensated Wilson disease.
AB  - Acute decompensated Wilson disease presenting as fulminant liver failure is a
      life-threatening condition for which liver transplantation is the ultimate
      treatment. It is listed as a status 1 indication according to the United Network
      for Organ Sharing classification. A massive amount of copper released during the
      attack induces hemolytic anemia and acute renal failure. Conventional chelating
      therapy attempting to remove copper from the patient is not satisfactory because
      there is inadequate time for these drugs to take action and patients are usually
      oliguric. The Molecular Adsorbents Recirculating System (MARS) is a form of
      modified dialysis that removes putative albumin-bound toxins associated with
      liver failure. It is believed that extracorporeal albumin dialysate absorbs the
      circulating copper molecules that are trapped in the patient's circulation. We
      report 2 patients with acute decompensated Wilson disease treated with MARS. In
      the first case, the patient was started on MARS once conventional treatment
      failed. A significant amount of copper was removed from her circulatory system,
      and her condition stabilized afterwards. The treatment gained her extra time, and
      she was eventually bridged to liver transplantation. In the second case, the
      patient was started on MARS treatment early in the course of his illness, and his
      condition soon stabilized after the treatment. He was able to return to his home
      country for liver transplantation. In both cases, MARS was used as a means of
      preventing deterioration rather than salvaging devastation. In conclusion, MARS
      may confer benefits to patients with acute decompensated Wilson disease if it is
      started early in the course of illness.

PMID- 18825712
TI  - High mobility group box 1 protein as a marker of hepatocellular injury in human
      liver transplantation.
AB  - High mobility group box 1 protein (HMGB1), a cytokine actively secreted by
      phagocytes and passively released from necrotic cells, is an inflammatory
      mediator in experimental hepatic ischemia/reperfusion injury. We characterized
      its expression in human liver transplantation. In 20 patients, in addition to
      systemic samples, blood was drawn from portal and hepatic veins during and after
      reperfusion to assess changes within the graft. Plasma HMGB1, tumor necrosis
      factor alpha (TNF-alpha), and interleukin-6 (IL-6) levels were measured, and
      HMGB1 immunohistochemistry was performed on biopsies taken before and after
      reperfusion. Plasma HMGB1 was undetectable before reperfusion, and levels in
      systemic circulation peaked after graft reperfusion. At portal declamping, HMGB1
      levels were substantially higher in the caval effluent [188 (80-371) ng/mL] than
      in portal venous blood [0 (0-3) ng/mL, P < 0.001]. HMGB1 release from the graft
      continued thereafter. HMGB1 levels were not related to TNF-alpha or IL-6 levels.
      HMGB1 expression was up-regulated in biopsies taken after reperfusion (P =
      0.020), with intense hepatocyte and weak neutrophil staining. HMGB1 levels in
      hepatic venous blood correlated with graft steatosis (r = 0.497, P = 0.03) and
      peak postoperative alanine aminotransferase levels (r = 0.588, P = 0.008). Our
      results indicate that HMGB1 originates from the graft and is a marker of
      hepatocellular injury in human liver transplantation.

PMID- 18825713
TI  - Incidence and diagnosis of active toxoplasma infection among liver transplant
      recipients in Western Turkey.
AB  - Toxoplasmosis is a serious and potentially life-threatening disease in liver
      transplant recipients while they are immunosuppressed. We report the clinical and
      laboratory findings related to active toxoplasma infection associated with 40
      immunosuppressed liver transplant procedures that took place over a 12-month
      period at a major transplant unit in Izmir, Turkey. Twenty-seven (67.5%) of the
      40 transplant recipients were found to be seropositive for toxoplasma infection
      and therefore at risk of reactivated infection. From the serological status of
      the donors, which was ascertained in 38 of 40 cases, we identified 3 (7.9%) of 38
      transplants to be from a seropositive donor to a seronegative recipient. In 10
      (26.3%) of 38 transplants, both the donor and recipient were seronegative, and
      this excluded toxoplasma as a risk. A comparison of real-time polymerase chain
      reaction (PCR) and nested PCR was undertaken in combination with a range of
      serological assays (the Sabin-Feldman dye test, enzyme immunoassay immunoglobulin
      M, and immunosorbent agglutination assay immunoglobulin M). Ethylene diamine
      tetraacetic acid blood samples from 3 of the 30 recipients at risk from
      toxoplasma were found positive by PCR, but only 1 of these was found positive in
      both assays. Among the 3 PCR-positive patients, immunoglobulin M and
      immunoglobulin G antibody levels increased in only 1 patient. Correlations
      between symptoms, laboratory findings, and clinical management (use of anti
      toxoplasma therapy) are presented. Our findings suggest that toxoplasma presents
      a significant risk to our liver transplant population and that PCR is a helpful
      addition in identifying active infections and hence in informing clinical
      management decisions.

PMID- 18825714
TI  - Extrahepatic hepatitis C virus after transplantation: diabetes and renal
      dysfunction.
AB  - 1. Insulin resistance is associated with hepatitis C virus infection and plays a
      role in the progression of hepatitis C virus-related liver disease and fibrosis.
      2. Treating insulin resistance and achieving glycemic control will be important
      for improving post-liver transplant morbidity and mortality: control of the
      hepatitis C virus will help to accomplish this. 3. The main renal complication of
      hepatitis C virus is membranoproliferative glomerulonephritis, and this occurs
      most commonly in the setting of mixed cryoglobulinemia.

PMID- 18825715
TI  - Risk of extended criteria donors in hepatitis C virus-positive recipients.
AB  - 1. An extended criteria donor is a donor who has certain characteristics that
      have an impact on the short-term and long-term outcomes of the recipient. 2.
      Grafts with reduced quality from extended criteria donors may show an increased
      sensitivity toward additional damaging events such as ischemia/reperfusion
      injury, acute rejection episodes, or recurrent hepatitis C. 3. Extended criteria
      donor features potentially having an impact on outcome in hepatitis C virus
      recipients include donor age, allograft steatosis, prolonged warm and cold
      ischemia times, and donation after cardiac death. 4. In hepatitis C virus
      positive recipients, there is strong evidence showing an association between the
      use of grafts from older donors (>40-50 years) and increased fibrosis progression
      and reduced graft and patient survival. 5. A potential strategy to minimize the
      severity of recurrence is to optimize donor selection. Donor age limitations and
      exclusion of moderately to severely steatotic livers, in addition to minimization
      of ischemic times, may reduce the likelihood of preservation injury as well as
      biliary complications, which, in turn, have been shown to have an impact on
      survival for hepatitis C virus-positive recipients. 6. Although a donor graft
      biopsy is not required if an extended criteria donor is used, it is highly
      recommended when hepatitis C virus-positive donors, donation after cardiac death,
      or multiple extended criteria donor factors are involved.

PMID- 18825719
TI  - Management of patients with decompensated hepatitis B virus associated
      [corrected] cirrhosis.
AB  - 1. Hepatitis B virus replication is associated with a severe outcome in patients
      with decompensated cirrhosis. 2. Viral suppression induced by antivirals results
      in a clinical improvement that allows liver transplantation to be delayed or
      avoided. 3. Early treatment intervention is mandatory in patients with
      decompensated cirrhosis because of the delay in the restoration of liver
      functions. 4. Lamivudine is no longer the drug of choice because the initial
      enthusiasm has been tempered by the high rate of resistance development. 5. Early
      add-on therapy with adefovir allows us to rescue lamivudine resistance, but its
      use may be limited by nephrotoxicity. 6. Studies are ongoing with the newer
      generation of antivirals (telbivudine, tenofovir, entecavir, and emtricitabine)
      in monotherapy or in combination to determine the best strategy for achieving
      rapid and prolonged suppression of viral replication. These improved strategies
      should enhance treatment success enough to obtain clinical stabilization, to
      delay or prevent the need for transplantation, and to reduce the risk of
      hepatitis B virus recurrence on the graft.AASLD.

PMID- 18825720
TI  - How to diagnose and treat hepatitis B virus antiviral drug resistance in the
      liver transplant setting.
AB  - 1. Hepatitis B virus variants with antiviral drug-resistant mutations and/or
      hepatitis B immune globulin-resistant mutations are the main cause of hepatitis B
      virus reinfections post-liver transplant. 2. Early diagnosis of antiviral drug
      resistance and prompt initiation of rescue therapy are important in preventing
      hepatitis flares and hepatic decompensation. 3. Virologic breakthrough is the
      first indication of antiviral drug resistance. 4. Genotypic resistance testing
      should be performed when possible to avoid unnecessary modification of treatment
      in patients who do not have confirmed antiviral drug resistance and to permit
      appropriate selection of rescue therapy in those who have confirmed antiviral
      drug resistance. 5. Choice of rescue therapy requires knowledge of the past
      history of hepatitis B virus treatments and virologic response to those
      treatments, patterns of mutations detected at the time of virologic breakthrough,
      and in vitro cross-resistance data. 6. Occurrence of antiviral drug resistance
      can be reduced by the use of the most potent nucleos(t)ide analogue(s) with the
      highest genetic barrier to resistance, emphasis of medication compliance, and
      close monitoring of virologic response.

PMID- 18825721
TI  - Liver transplantation for hepatitis B: what is the best hepatitis B immune
      globulin/antiviral regimen?
AB  - 1. Prophylaxis using the combination of lamivudine and high-dose intravenous
      hepatitis B immunoglobulin (approximately 10,000 IU monthly) reduces the long
      term risk of recurrence of hepatitis B in hepatitis B surface antigen-positive
      transplant recipients to 5% to 10%. However, this therapy is expensive and
      inconvenient for patients. 2. Recent studies have shown that similar results can
      be obtained, at far less cost, with much lower doses of intramuscular hepatitis B
      immune globulin (400-800 IU monthly) in combination with pretransplant and
      posttransplant lamivudine therapy. 3. The development of lamivudine resistance
      pre-transplant can lead to hepatic decompensation and increases the risk of
      posttransplant recurrence in patients receiving hepatitis B immune
      globulin/lamivudine prophylaxis. Newer nucleos(t)ide analogues with lower
      resistance rates such as entecavir, adefovir, and tenofovir should therefore
      replace lamivudine in hepatitis B prophylaxis. 4. Combination therapy with these
      newer agents and low-dose intramuscular hepatitis B immune globulin is likely to
      be the most cost effective hepatitis B immune globulin-containing regimen for the
      prevention of hepatitis B recurrence post-transplant. 5. Some form of hepatitis B
      virus prophylaxis needs be continued indefinitely post-transplant. However, the
      use of antivirals with very low rates of drug resistance will make it possible to
      stop hepatitis B immune globulin therapy in many patients currently receiving
      hepatitis B immune globulin/nucleos(t)ide combination therapy.

PMID- 18825722
TI  - Do we really need long-term hepatitis B hyperimmune globulin? What are the
      alternatives?
AB  - 1. The outcomes of liver transplantation for patients with hepatitis are the best
      for any diagnosis. 2. Prevention of HBV re-infection is the key to excellent
      outcomes after liver transplantation. 3. The use of hepatitis B immunoglobulin to
      prevent HBV re-infection is effective, but costly and with side effects. 4.
      Effective prophylaxis against HBV re-infection can now be accomplished with
      combination nucleoside/nucleotide anti-virals.

PMID- 18825723
TI  - Virology and pathogenesis of hepatitis C virus recurrence.
AB  - 1. In hepatitis C virus (HCV)-infected patients undergoing liver transplantation
      (LT), the virus infects the liver graft immediately after transplantation. The
      main source of HCV infection is circulating virions. Nevertheless, some data
      suggest that HCV present in extrahepatic compartments may contribute to HCV
      infection in some cases of hepatitis C recurrence. 2. Studies on early kinetics
      have shown that HCV replication starts a few hours after transplantation and that
      HCV-RNA concentrations increase a few hours or days after the procedure,
      suggesting that HCV has an enormous ability to adapt to the new environment. 3.
      The quasispecies population may change significantly after transplantation, most
      likely because of the need to adapt to a new environment. There are no conclusive
      data supporting the role of HCV quasispecies composition and disease outcomes. 4.
      Persistence of HCV infection is the rule after transplantation. This is due to
      immunosuppression and to the immune exhaustion of the previously exposed immune
      system. 5. In general, HCV is not thought to be directly cytopathic. Thus, it is
      believed that the immune response against HCV causes liver damage. However,
      understanding the mechanisms of liver damage in HCV-infected LT recipients is
      extremely complex because of the existence of a human leukocyte antigen
      mismatched organ, the preexisting virus-specific T cells that may be
      dysfunctional and/or tolerized, and the immunosuppression. 6. Despite the
      possible effect of immune-mediated liver damage, it is clear that strong
      immunosuppression is associated with severe forms of hepatitis C recurrence
      (cholestatic hepatitis, fibrosing cholestatic hepatitis, and accelerated fibrosis
      progression). Thus, in the absence of a strong anti-HCV immune response, HCV is
      able to directly (HCV proteins) or indirectly (cytokines) produce liver damage.
      7. The activation of stellate cells and accelerated deposition of fibrosis are
      the final consequences of HCV infection in the graft. There are several
      mechanisms that may act synergistically to activate and perpetuate stellate cell
      activation in the setting of LT: ischemia-reperfusion damage, old donor age, HCV
      proteins, cholestasis, rejection, infection with other viruses (cytomegalovirus),
      and immune-mediated injury.

PMID- 18825724
TI  - The natural history of recurrent hepatitis C and what influences this.
AB  - 1. Liver failure and liver cancer from chronic hepatitis C are the most common
      indications for liver transplantation and numbers of both are projected to double
      over the next 20 years. 2. Recurrent hepatitis C infection of the allograft is
      universal and immediate following liver transplantation and associated with
      accelerated progression to cirrhosis, graft loss and death. 3. Graft and patient
      survival is reduced in liver transplant recipients with recurrent HCV infection
      compared to HCV-negative recipients. 4. The natural history of chronic hepatitis
      C is accelerated following liver transplantation compared C, with 20% progressing
      to cirrhosis by 5 years. However, the rate of fibrosis progression is not uniform
      and may increase over time. 5. The rates of progression from cirrhosis to
      decompensation and from decompensation to death are also accelerated following
      liver transplantation. 6. Multiple host, donor and viral factors are associated
      with rapid fibrosis progression and HCV-related graft failure. 7. Over the last
      decade, graft and patient survival rates have improved following liver
      transplantation for non-HCV disease but not for HCV-cirrhosis. This may reflect
      worsening donor quality and changes in immunosuppression strategies over recent
      years. 8. Viral eradication by antiviral therapy prevents disease progression and
      improves survival. 9. The severity of recurrent hepatitis C at one year post
      transplant predicts subsequent progression to cirrhosis. Annual protocol biopsies
      are recommended to help determine need for antiviral therapy. 10. The projected
      impact of recurrent hepatitis C on graft and patient survival can only be avoided
      by the development of safe and effective antiviral strategies which can both
      prevent initial graft infection and eradicate established hepatitis C recurrence.

PMID- 18825725
TI  - First occurrence of cylindrospermopsin in freshwater in France.
AB  - Eleven waterbodies in Western France dominated by cyanobacteria of the genera
      Aphanizomenon and Anabaena were analyzed in September 2006 for microcystins (MC)
      and cylindrospermopsin (CYN). CYN was detected for the first time in France in
      four of them in the presence of Aphanizomenon flos-aquae and in the presence of
      Anabaena planctonica in the other. The intracellular concentrations of CYN
      measured by LC-MS/MS ranged between 1.55 and 1.95 microg/L. The occurrence of CYN
      represents an additional health hazard to MC especially because Aphanizomenon
      flos-aquae is the third most common species in freshwaters in France.

PMID- 18825726
TI  - Lysosomal membrane response of earthworm, Eisenia fetida, to arsenic
      contamination in soils.
AB  - Earthworm (Eisenia fetida) were exposed to sandy soils contaminated with arsenate
      (0.01-0.3 micromol g(-1)) for 28 days. Lysosomal membrane stability was used as a
      biomarker to determine the applicability of neutral-red retention times (NRRTs)
      for arsenic (As) toxicity to earthworm in soils. Total As and As speciation were
      analyzed to evaluate dose-response relationship between As accumulation and NRRTs
      and to observe the role of As metabolism in earthworms on a subcellular level
      toxicity. Significant decrease of NRRTs was found with the increasing As
      concentration in soils (ANOVA, P < 0.05). Adverse effects on earthworm survival
      and growth did not occur when exposed to 0.1 and 0.05 micromol g(-1) at 14 and 28
      days, respectively, whereas NRRTs showed significant reduction from the control,
      as was readily bioconcentrated in the reduced form of As(III) in earthworms and
      clear dose-response relationships were found for As body burden and NRRTs.
      Therefore, it is possible to conclude that As has an adverse effect on lysosomal
      membrane of coelomocytes, and NRRT assay is a potentially applicable method to
      assess As toxicity as an early warning tool. Also, sequestered As in the form of
      As(III)-thiol complex can be expected to cause an adverse effect on lysosomal
      membrane stability.

PMID- 18825727
TI  - Folic acid or combination of folic acid and vitamin B(12) prevents short-term
      arsenic trioxide-induced systemic and mitochondrial dysfunction and DNA damage.
AB  - The effect of folic acid and folic acid + vitamin B(12) supplementation upon
      short-term arsenic-induced systemic and pancreatic islet cell mitochondria
      oxidative stress was investigated in male rats. Arsenic trioxide was administered
      orally at a dose of 3 mg kg body weight(-1) day(-1) for 30 days, and folic acid
      and vitamin B(12) were administered at a dose of 36 and 0.63 microg kg body
      weight(-1) day(-1), respectively, for 30 days. Compared to control, arsenic
      treated group showed a significant increase in the levels of systemic oxidative
      markers, malondialdehyde (MDA), nitric oxide (NO), and hydroxyl radical (OH(-))
      formation, which were found decreased significantly after supplementation either
      with folic acid or a combination of folic acid + vitamin B(12). Similar
      supplementations were found effective against arsenic-induced oxidative marker
      changes (MDA, NO, and OH(-)) in pancreatic islet cell mitochondria. Also, low
      activities of antioxidant defense enzymes such as superoxide dismutase and
      catalase, and level of antioxidant glutathione, all could regain significantly on
      supplementations both against systemic and islet cell mitochondria oxidative
      stress. Results of agarose-gel electrophoresis of DNA from lymphocytes and islet
      cells of arsenic-exposed rats showed DNA smearing, which could be reduced with
      simultaneous administration either with folic acid or a combination of folic acid
      + vitamin B(12). Significantly, similar supplementations were found effective in
      increasing the urinary clearance of arsenic. Together, these results indicate
      that folic acid and vitamin B(12) may be effective to reduce the arsenic-induced
      damage at molecular target level.

PMID- 18825728
TI  - Immunizations and infectious diseases in pediatric liver transplantation.

PMID- 18825729
TI  - In vitro cytotoxicities of ionic liquids: effect of cation rings, functional
      groups, and anions.
AB  - In vitro cytotoxicities were measured for ionic liquids (ILs) containing various
      cations and anions using the MCF7 human breast cancer cell line. We measured the
      cytotoxicities of ionic liquids containing the cations pyridinium, pyrrolidinium,
      piperidinium, or imidazolium with various alkyl chain lengths, and the anions
      bromide, bis(trifluoromethanesulfone)imide (Tf(2)N), trifluoromethylsulfonate
      (TfO), or nonafluoromethylsulfonate (NfO). Three new hydrophobic, task-specific
      ionic liquids (TSILs), namely, [MBCNPip](+)[Tf(2)N](-), [MPS(2)Pip](+)[Tf(2)N](
      ), and [MPS(2)Pyrro](+)[Tf(2)N](-) designed for metal-ion extraction were also
      evaluated. IC(50) values of the ionic liquids toward the MCF7 cells ranged from 8
      microM to 44 mM. The toxicity depended significantly on the nature of the cations
      and anions, especially when the cations contained a long side chain. TSILs
      studied in this work were less toxic than the classical ILs.

PMID- 18825730
TI  - An extract of Hydrilla verticillata and associated epiphytes induces avian
      vacuolar myelinopathy in laboratory mallards.
AB  - Avian vacuolar myelinopathy (AVM) is a neurological disease affecting bald eagles
      (Haliaeetus leucocephalus), American coots (Fulica americana), waterfowl, and
      other birds in the southeastern United States. The cause of the disease is
      unknown, but is thought to be a naturally produced toxin. AVM is associated with
      aquatic macrophytes, most frequently hydrilla (Hydrilla verticillata), and
      researchers have linked the disease to an epiphytic cyanobacterial species
      associated with the macrophytes. The goal of this study was to develop an
      extraction protocol for separating the putative toxin from a hydrilla
      cyanobacterial matrix. Hydrilla samples were collected from an AVM-affected
      reservoir (J. Strom Thurmond Lake, SC) and confirmed to contain the etiologic
      agent by mallard (Anas platyrhynchos) bioassay. These samples were then extracted
      using a solvent series of increasing polarity: hexanes, acetone, and methanol.
      Control hydrilla samples from a reference reservoir with no history of AVM (Lake
      Marion, SC) were extracted in parallel. Resulting extracts were administered to
      mallards by oral gavage. Our findings indicate that the methanol extracts of
      hydrilla collected from the AVM-affected site induced the disease in laboratory
      mallards. This study provides the first data documenting for an "extractable" AVM
      inducing agent.

PMID- 18825731
TI  - The relationships among self-esteem, stress, coping, eating behavior, and
      depressive mood in adolescents.
AB  - The prevalence of adolescent overweight is significant, almost 25% in some
      minorities, and often is associated with depressive symptoms. Psychological and
      psychosocial factors as well as poor coping skills have been correlated with
      unhealthy eating and obesity. The purpose of this study was to examine
      relationships among self-esteem, stress, social support, and coping; and to test
      a model of their effects on eating behavior and depressive mood in a sample of
      102 high school students (87% minority). Results indicate that (a) stress and low
      self-esteem were related to avoidant coping and depressive mood, and that (b) low
      self-esteem and avoidant coping were related to unhealthy eating behavior.
      Results suggest that teaching adolescents skills to reduce stress, build self
      esteem, and use more positive approaches to coping may prevent unhealthy eating
      and subsequent obesity, and lower risk of depressive symptoms.

PMID- 18825732
TI  - Bile duct stones and casts after liver transplantation: Different entities but
      similar prevention strategy?

PMID- 18825733
TI  - Nurse staffing and medication errors: cross-sectional or longitudinal
      relationships?
AB  - We used autoregressive latent trajectory (ALT) modeling to examine the
      relationship between change in nurse staffing and change in medication errors
      over 6 months in 284 general medical-surgical nursing units. We also investigated
      the impact of select hospital and nursing unit characteristics on the baseline
      level and rate of change in medication errors. We found essentially no support
      for a nurse staffing-medication error relationship either cross-sectionally or
      longitudinally. Few hospital or nursing unit characteristics had significant
      relationships to either the baseline level or rate of change in medication
      errors. However, ALT modeling is a promising technique that can promote a deeper
      understanding of the theoretically complex relationships that may underlie the
      nurse staffing-medication error relationship.

PMID- 18825737
TI  - High-tech applications of self-assembling supramolecular nanostructured gel-phase
      materials: from regenerative medicine to electronic devices.
AB  - It is likely that nanofabrication will underpin many technologies in the 21st
      century. Synthetic chemistry is a powerful approach to generate molecular
      structures that are capable of assembling into functional nanoscale
      architectures. There has been intense interest in self-assembling low-molecular
      weight gelators, which has led to a general understanding of gelation based on
      the self-assembly of molecular-scale building blocks in terms of non-covalent
      interactions and packing parameters. The gelator molecules generate hierarchical,
      supramolecular structures that are macroscopically expressed in gel formation.
      Molecular modification can therefore control nanoscale assembly, a process that
      ultimately endows specific material function. The combination of supramolecular
      chemistry, materials science, and biomedicine allows application-based materials
      to be developed. Regenerative medicine and tissue engineering using molecular
      gels as nanostructured scaffolds for the regrowth of nerve cells has been
      demonstrated in vivo, and the prospect of using self-assembled fibers as one
      dimensional conductors in gel materials has captured much interest in the field
      of nanoelectronics.

PMID- 18825741
TI  - The capacity of the TNF family members 4-1BBL, OX40L, CD70, GITRL, CD30L and
      LIGHT to costimulate human T cells.
AB  - Activating signals generated by members of the tumour necrosis factor receptor
      superfamily upon interaction with their cognate ligands play important roles in T
      cell responses. Members of the tumour necrosis factor family namely 4-1BBL,
      OX40L, CD70, GITRL, LIGHT and CD30L have been described to function as
      costimulatory molecules by binding such receptors on T cells. Using our recently
      described system of T-cell stimulator cells we have performed the first study
      where all these molecules have been assessed and compared regarding their
      capacity to costimulate proliferation and cytokine production of human T cells. 4
      1BBL, which we found to be the most potent molecule in this group, was able to
      mediate sustained activation and proliferation of human T cells. OX40L and CD70
      were also strong inducers of T-cell proliferation, whereas the costimulatory
      capacity of human GITRL was significantly lower. Importantly CD30L and LIGHT
      consistently failed to act costimulatory on human T cells, and we therefore
      suggest that these molecules might be functionally distinct from the
      costimulatory members of this family.

PMID- 18825742
TI  - Freeze-and-thaw-disrupted tumour cells impair the responsiveness of DC to TLR
      stimulation.
AB  - Cancer immunotherapy aims at inducing immune responses against tumour-associated
      antigens that mediate the eradication of tumour cells. For successful vaccination
      against antigens expressed by the tumour, the immune system has to be provided
      with sufficient amounts of these antigens in connection with strong
      immunostimulatory signals such as toll-like receptor (TLR) ligands. Tumour cells
      represent a convenient source of relevant tumour-associated antigens but can have
      suppressive properties. In this study, we explored how different forms of tumour
      cell material influence the activation of dendritic cells (DC), which play a
      crucial role in the induction of anti-tumour immune responses. We show that
      freeze-and-thaw-disrupted tumour cells inhibit DC activation in response to TLR
      stimulation, a phenomenon that is only partially seen with non-disrupted control
      cells. This suppression of DC stimulation is independent of tumour cell- and
      species-specific factors. We tested the hypothesis that phosphatidylserine on
      cells with disrupted membrane integrity mediates inhibition of TLR-induced DC
      activation. Our experimental evidence indicates that phosphatidylserine is not
      involved in the inhibition of TLR-mediated DC activation by freeze-and-thaw
      disrupted cells. The inhibitory activity associated with disrupted tumour cells
      could explain why such preparations are less effective tumour vaccines than
      apoptotic tumour cells.

PMID- 18825743
TI  - Efficacy of IL-2- versus IL-15-stimulated CD8 T cells in adoptive immunotherapy.
AB  - We determined the efficacy of in vitro expanded P14 TCR transgenic CD8 T cells to
      mediate tumor cell elimination and to protect against viral infection in mice.
      Contrary to previous studies, an adoptive transfer model without lymphodepletion,
      vaccination or cytokine treatment was used. Antigen-activated P14 T cells
      cultured in IL-2-containing medium for 7 days (P14IL-2) exhibited potent effector
      cell functions in vitro but did not confer protection against melanoma growth or
      viral infection. In contrast, P14 T cells cultured in IL-15 (P14IL-15) were
      highly effective in vivo although they displayed only moderate effector functions
      in vitro. Therapeutic efficacy correlated with the survival of the transferred T
      cells in the recipients: P14IL-2 cells disappeared rapidly whereas P14IL-15 cells
      persisted for prolonged time. Decreasing the IL-2 concentration in the culture
      media improved in vivo survival and efficacy but also lowered the cell yield of
      the cultures. Finally, we could extend the findings with monoclonal P14 T cells
      to polyclonal CD8 T cells. Thus, in vitro expansion of antigen-specific CD8 T
      cells in IL-15 allowed the generation of substantial numbers of T cells without
      inducing terminally differentiated effector cells that turned out to be
      unfavorable in the transfer model examined here.

PMID- 18825744
TI  - IFN-beta regulates CD73 and adenosine expression at the blood-brain barrier.
AB  - IFN-beta treatment reduces the relapse rate in MS but its mechanism of action
      remains incompletely understood. Our aim was to clarify the beneficial effect of
      IFN-beta in the treatment of MS. We assessed the influence of IFN-beta treatment
      on (i) CD73 expression on the surface of primary cultures of human blood-brain
      barrier endothelial cells (BBB-EC) and human astrocytes using immunofluorescence
      staining and flow cytometry, (ii) transmigration of CD4+ T lymphocytes using an
      in vitro model of BBB and (iii) CD73 enzyme activity, i.e. ecto-5'-nucleotidase
      activity in the serum of MS patients using a radiochemical assay. IFN-beta
      increases the expression of ecto-5'-nucleotidase both on BBB-EC and astrocytes.
      As a consequence, lymphocyte transmigration through BBB-EC is reduced.
      Importantly, this reduction can be reversed using alpha,beta-methyleneadenosine
      5'-diphosphate, a specific inhibitor of ecto-5'-nucleotidase. CD73 is strongly
      expressed in microvasculature in samples of postmortem MS brain and, moreover, in
      the majority of MS patients there was a clear upregulation both in the soluble
      serum ecto-5'-nucleotidase activity and skin microvascular CD73 expression after
      IFN-beta treatment. Upregulation of ecto-5'-nucleotidase and a subsequent
      increase in adenosine production might contribute to the beneficial effects of
      IFN-beta on MS via enhancing the endothelial barrier function.

PMID- 18825745
TI  - Effector CD8+ T cells activated in vitro confer immediate and long-term tumor
      protection in vivo.
AB  - We studied the ability of CD8+ T cells activated in vitro to mediate tumor
      protection after transfer into adoptive hosts. TCR transgenic CD8+ T cells were
      activated in culture with DC and specific peptide antigen, and briefly expanded
      in IL-2 containing medium. Cultured cells acquired a CD44hiCD62Llo phenotype, and
      following in vivo transfer they preferentially homed to non-lymphoid tissues and
      spleen. In vivo, their numbers declined between day 0 and day 20, and then
      remained relatively stable from day 20 to day 90. Over time, many of the injected
      cells re-expressed CD62L, and acquired the ability to localize to secondary
      lymphoid organs. Transferred T cells underwent low-level proliferation, expressed
      IL-7Ralpha and IL-15Rbeta, were cytotoxic in vivo, and retained the ability to
      produce IL-2, IFN-gamma and TNF-alpha upon ex vivo restimulation. In addition,
      transferred T cells conferred a high degree of tumor protection, which was
      greatest immediately after injection, and remained significant even when tumor
      was given 90 days after T-cell transfer. We conclude that in vitro generated
      effector T cells can mediate immediate and long-term tumor protection, and
      develop into long-lived memory T-cell populations in vivo.

PMID- 18825746
TI  - DNA polymerase eta is a limiting factor for A:T mutations in Ig genes and
      contributes to antibody affinity maturation.
AB  - DNA polymerase eta (POLH) is required for the generation of A:T mutations during
      the somatic hypermutation of Ig genes in germinal center B cells. It remains
      unclear, however, whether POLH is a limiting factor for A:T mutations and how the
      absence of POLH might affect antibody affinity maturation. We found that the
      heterozygous Polh+/- mice exhibited a significant reduction in the frequency of
      A:T mutations in Ig genes, with each type of base substitutions at a level
      intermediate between the Polh+/+ and Polh(-/-) mice. These observations suggest
      that Polh is haplo-insufficient for the induction of A:T mutations in Ig genes.
      Intriguingly, there was also a reduction of C to T and G to A transitions in
      Polh+/- mice as compared with WT mice. Polh(-/-) mice produced decreased serum
      titers of high-affinity antibodies against a T-dependent antigen, which was
      associated with a significant reduction in the number of plasma cells secreting
      high-affinity antibodies. Analysis of the V region revealed that aa substitutions
      caused by A:T mutations were greatly reduced in Polh(-/-) mice. These results
      demonstrate that POLH is a limiting factor for A:T mutations and contributes to
      the efficient diversification of Ig genes and affinity maturation of antibodies.

PMID- 18825747
TI  - Th memory for interleukin-17 expression is stable in vivo.
AB  - Based on the memory for the re-expression of certain cytokine genes, different
      subsets of Th cells have been defined. In Th type 1 (Th1) and Th2 memory
      lymphocytes, the genes for the cytokines interferon-gamma and interleukin (IL)-4
      are imprinted for expression upon restimulation by the expression of the
      transcription factors T-bet and GATA-3, respectively, and epigenetic modification
      of the cytokine genes. In Th17 cells, IL-17 expression is dependent on the
      transcription factors RORgammat and RORalpha. Here, we analyze the stability and
      plasticity of IL-17 memory in Th17 cells. We have developed a cytometric IL-17
      secretion assay for the isolation of viable Th cells secreting IL-17. For Th17
      cells generated in vitro, IL-17 expression itself is dependent on continued TGF
      beta/IL-6 or IL-23 signaling and is blocked by interferon-gamma and IL-4
      signaling. In response to IL-12 and IL-4, in vitro generated Th17 cells are
      converted into Th1 or Th2 cells, respectively. Th17 cells isolated ex vivo,
      however, maintain their IL-17 memory upon subsequent in vitro culture, even in
      the absence of IL-23. Their cytokine memory is not regulated by IL-12 or IL-4.
      Th17 cells generated in vivo are a stable and distinct lineage of Th cell
      differentiation.

PMID- 18825748
TI  - Pulmonary stromal cells induce the generation of regulatory DC attenuating T-cell
      mediated lung inflammation.
AB  - The tissue microenvironment may affect the development and function of immune
      cells such as DC. Whether and how the pulmonary stromal microenvironment can
      affect the development and function of lung DC need to be investigated.
      Regulatory DC (DCreg) can regulate T-cell response. We wondered whether such
      regulatory DC exist in the lung and what is the effect of the pulmonary stromal
      microenvironment on the generation of DCreg. Here we demonstrate that murine
      pulmonary stromal cells can drive immature DC, which are regarded as being widely
      distributed in the lung, to proliferate and differentiate into a distinct subset
      of DCreg, which express high levels of CD11b but low levels of MHC class II (I
      A), CD11c, secrete high amounts of IL-10, NO and prostaglandin E2 (PGE2) and
      suppress T-cell proliferation. The natural counterpart of DCreg in the lung with
      similar phenotype and regulatory function has been identified. Pulmonary stroma
      derived TGF-beta is responsible for the differentiation of immature DC to DCreg,
      and DCreg-derived PGE2 contributes to their suppression of T-cell proliferation.
      Moreover, DCreg can induce the generation of CD4+CD25+Foxp3+ Treg. Importantly,
      infusion with DCreg attenuates T-cell-mediated eosinophilic airway inflammation
      in vivo. Therefore, the pulmonary microenvironment may drive the generation of
      DCreg, thus contributing to the maintenance of immune homoeostasis and the
      control of inflammation in the lung.

PMID- 18825749
TI  - Reduction of cPLA2alpha overexpression: an efficient anti-inflammatory therapy
      for collagen-induced arthritis.
AB  - Cytosolic phospholipase A2alpha (cPLA2) plays an important role in the
      development of several inflammatory diseases. The aim of the present study is to
      determine whether inhibition of cPLA2 expression, using specific antisense
      oligonucleotides against cPLA2 (antisense), is efficient in reducing inflammation
      after its development. Two mouse models of inflammation were included in the
      study: thioglicolate peritonitis and collagen-induced arthritis (CIA). The
      antisense was found to be specific and efficient in inhibiting cPLA2 expression
      and NADPH oxidase activity ex vivo in peritoneal phagocytes. Immunoblotting and
      immunohistochemistry analysis showed a significant elevation in cPLA2 expression
      in the inflamed joints of collagen-induced arthritis mice localized in cell
      infiltrate, chondrocytes and the surrounding skin and skeletal muscle. Similarly,
      the cPLA2 metabolite, leukotriene B4, accumulated in the peritoneal cavity of
      mice with peritonitis. Inhibition of elevated cPLA2 expression after development
      of inflammation by intravenous administration of antisense resulted in a dramatic
      reduction in inflammation and a significant reduction in neutrophils recruitment
      to the site of inflammation in both mouse models of inflammation. Our results
      demonstrate the critical role of cPLA2 for the duration of inflammation and
      suggest that inhibition of cPLA2 expression by antisense oligonucleotides may
      serve as an efficient treatment of inflammatory diseases.

PMID- 18825750
TI  - A novel CD11c.DTR transgenic mouse for depletion of dendritic cells reveals their
      requirement for homeostatic proliferation of natural killer cells.
AB  - Dendritic cells (DC) are known to support the activation of natural killer (NK)
      cells. However, little is known about the role for DC in NK-cell homeostasis. In
      order to investigate this question, a novel bacterial artificial chromosome
      transgenic mouse model was generated in which the diphtheria toxin receptor is
      expressed under the CD11c promoter. In these mice efficient DC depletion can be
      achieved over prolonged periods of time by multiple injections of diphtheria
      toxin. We show here that NK cells require DC for full acquisition of effector
      function in vivo in response to the bacterial-derived TLR ligand CpG.
      Importantly, DC were found to play an instrumental role for maintaining normal
      homeostasis of NK cells. This is achieved by IL-15 production by DC, which
      supports the homeostatic proliferation of NK cells.

PMID- 18825751
TI  - Lack of galectin-3 alters the balance of innate immune cytokines and confers
      resistance to Rhodococcus equi infection.
AB  - Galectin-3 is a beta-galactoside-binding lectin implicated in the fine-tuning of
      innate immunity. Rhodococcus equi, a facultative intracellular bacterium of
      macrophages, causes severe granulomatous bronchopneumonia in young horses and
      immunocompromised humans. The aim of this study is to investigate the role of
      galectin-3 in the innate resistance mechanism against R. equi infection. The
      bacterial challenge of galectin-3-deficient mice (gal3-/-) and their wild-type
      counterpart (gal3+/+) revealed that the LD50 for the gal3(-/-) mice was about
      seven times higher than that for the gal3+/+ mice. When challenged with a
      sublethal dose, gal3(-/-) mice showed lower bacteria counts and higher production
      of IL-12 and IFN-gamma production, besides exhibiting a delayed although
      increased inflammatory reaction. Gal3(-/-) macrophages exhibited a decreased
      frequency of bacterial replication and survival, and higher transcript levels of
      IL-1beta, IL-6, IL-10, TLR2 and MyD88. R. equi-infected gal3+/+ macrophages
      showed decreased expression of TLR2, whereas R. equi-infected gal3(-/-)
      macrophages showed enhanced expression of this receptor. Furthermore, galectin-3
      deficiency in macrophages may be responsible for the higher IL-1beta serum levels
      detected in infected gal3(-/-) mice. Therefore galectin-3 may exert a regulatory
      role in innate immunity by diminishing IL-1beta production and thus affecting
      resistance to R. equi infection.

PMID- 18825753
TI  - Functional maturation of lamina propria dendritic cells by activation of NKT
      cells mediates the abrogation of oral tolerance.
AB  - We previously showed that although systemic administration of alpha
      galactosylceramide (alphaGalCer) or agonistic anti-CD40 induced functional
      maturation of dendritic cells (DC) in mesenteric lymph nodes, only the former
      treatment succeeded in breaking the induction of oral tolerance. In this study,
      we looked for the essential factor responsible for the disruption of oral
      tolerance. We found that lamina propria (LP)-DC was responsible for the oral OVA
      presentation and that Peyer's patch was not essential for the induction of oral
      tolerance. Therefore, we investigated the role of LP-DC. Treatment with
      alphaGalCer but not with anti-CD40 induced the full maturation of LP-DC at an
      early time point. This functional activation of LP-DC was mediated by strong
      activation of NKT cells that reside abundantly in the small intestinal lamina
      propria (SI-LP) and interferon-gamma partially contributed to the LP-DC
      activation. LP-DC isolated from alphaGalCer-treated OVA-fed mice induced the
      differentiation of naive CD4+ T cells into Th1 and Th2 and was associated with
      the reduced Foxp3+ population. In contrast, LP-DC isolated from anti-CD40-treated
      OVA-fed mice failed to generate Th cell differentiation but induced more Foxp3+
      CD4+ T cells. Our results demonstrate that triggered by NKT cells in SI-LP,
      functional maturation of Ag-capturing DC from SI-LP is necessary for the
      abrogation of oral tolerance induction.

PMID- 18825752
TI  - PD-1 ligands expressed on myeloid-derived APC in the CNS regulate T-cell
      responses in EAE.
AB  - Disease progression in experimental autoimmune encephalomyelitis (EAE) is
      regulated by programmed death receptor 1 (PD-1) and its ligands, B7-H1
      (programmed death ligand 1 (PD-L1)) and B7-DC (PD-L2). B7-H1 and B7-DC have
      negative regulatory effects upon binding PD-1 on activated T cells and B7-H1
      deficiency increases severity of both diabetes and EAE. However, the role of PD-L
      expression on different APC in the CNS in regulating local T-cell function during
      relapsing EAE has not been examined. Our data show that the majority of CNS CD4+
      T cells isolated during acute EAE are PD-1+, and T cells specific for relapse
      associated epitopes express PD-1 upon antigen stimulation in the CNS. B7-H1 and
      B7-DC are differentially expressed on discrete APC populations in the inflamed
      CNS. B7-H1 and PD-1 have mainly inhibitory functions on CNS T cells. B7-H1
      negatively regulates the stimulation of activated PD-1+ T(H) cells, in co
      cultures with microglia and different CNS-infiltrating APC presenting
      endogenously processed peptides. The preponderance of IFN-gamma+ versus IL-17+ T
      cells in the CNS of B7-H1(-/-) mice suggests that B7-H1 more selectively
      suppresses T(H)-1 than T(H)-17 responses in vivo. In contrast, blockade of B7-DC
      has less pronounced regulatory effects. Overall, the results demonstrate that B7
      H1 expressed by CNS myeloid APC negatively regulates T-cell activation during
      acute relapsing EAE.

PMID- 18825754
TI  - Plasmodium vivax parasites alter the balance of myeloid and plasmacytoid
      dendritic cells and the induction of regulatory T cells.
AB  - Immunity induced by Plasmodium vivax infections leads to memory T-cell
      recruitment and activation during subsequent infections. Here, we investigated
      the role of regulatory T cells (Treg) in coordination with the host immune
      response during P. vivax infection. Our results showed a significant increase in
      the percentage of FOXP3+ Treg, IL-10-secreting Type I Treg (Tr1) and IL-10 levels
      in patients with acute P. vivax infection as compared with those found in either
      naive or immune controls. The concurrent increase in the Treg population could
      also be reproduced in vitro using peripheral blood mononuclear cells from naive
      controls stimulated with crude antigens extracted from P. vivax-infected red
      blood cells. Acute P. vivax infections were associated with a significant
      decrease in the numbers of DC, indicating a general immunosuppression during P.
      vivax infections. However, unlike P. falciparum infections, we found that the
      ratio of myeloid DC (MDC) to plasmacytoid DC (PDC) was significantly lower in
      acute P. vivax patients than that of naive and immune controls. Moreover, the
      reduction in PDC may be partly responsible for the poor antibody responses during
      P. vivax infections. Taken together, these results suggest that P. vivax
      parasites interact with DC, which alters the MDC/PDC ratio that potentially leads
      to Treg activation and IL-10 release.

PMID- 18825755
TI  - Collagen type II is recognized by a pathogenic antibody through germline encoded
      structures.
AB  - Collagen type II (CII) is a cartilage-specific target of pathologic humoral
      autoimmune responses in rheumatoid arthritis as well as in the collagen-induced
      arthritis model. The aim of the present study is to investigate the critical
      amino acid residues conferring CII epitope specificity of the prototypic
      arthritogenic murine mAb CIIC1. A homology model of the CIIC1 single-chain
      antibody fragment (CIIC1scFv) in complex with its triple helical epitope was
      established. In silico predictions based on extensive molecular dynamics
      simulations were experimentally tested by the recombinant expression and
      functional analysis of CIIC1scFv containing alanine replacements allowing the
      identification of crucial CII-binding sites in the CDR2 and CDR3 regions of both
      heavy and light chains. Since the conversion of the CIIC1scFv sequence into the
      respective germline at all 13 somatically mutated positions did not affect its
      CII binding, our data indicate that potentially harmful cartilage-specific
      humoral autoimmunity could be germline encoded. The molecular modeling further
      demonstrates that the rigid collagen triple helix restricts the likelihood of
      molecular interactions with the CDR regions of the antibody considerably compared
      with globular antigens. These sterical constraints provide an explanation as to
      why somatic mutations in the arthritogenic autoantibody have no obvious impact on
      CII recognition.

PMID- 18825756
TI  - Synthesis of secondary enamides by ruthenium-catalyzed selective addition of
      amides to terminal alkynes.

PMID- 18825757
TI  - Tetrabutylammonium tetra(tert-butyl alcohol)-coordinated fluoride as a facile
      fluoride source.

PMID- 18825758
TI  - High-relaxivity MRI contrast agents: where coordination chemistry meets medical
      imaging.
AB  - The desire to improve and expand the scope of clinical magnetic resonance imaging
      (MRI) has prompted the search for contrast agents of higher efficiency. The
      development of better agents requires consideration of the fundamental
      coordination chemistry of the gadolinium(III) ion and the parameters that affect
      its efficacy as a proton relaxation agent. In optimizing each parameter, other
      practical issues, such as solubility and in vivo toxicity, must also be
      addressed, making the attainment of safe, high-relaxivity agents a challenging
      goal. This Minireview presents recent advances in the field, with an emphasis on
      gadolinium(III) hydroxypyridinone chelate complexes.

PMID- 18825759
TI  - Structural evolution of "S"-shaped [H4W22O74]12- and "section sign"-shaped
      [H10W34O116]18- isopolyoxotungstate clusters.

PMID- 18825760
TI  - Cool as a cucumber.

PMID- 18825761
TI  - Post-synthetic modification of tagged metal-organic frameworks.

PMID- 18825762
TI  - Copper-catalyzed highly enantioselective carbenoid insertion into Si-H bonds.

PMID- 18825763
TI  - The most stable and fully characterized functionalized heptacene.

PMID- 18825764
TI  - Probing biomolecules by laser-induced acoustic desorption: electrons at near zero
      electron volts trigger sugar-phosphate cleavage.

PMID- 18825765
TI  - Total synthesis of aburatubolactam A.

PMID- 18825766
TI  - Acceptor/acceptor-substituted diazo reagents for carbene transfers: cobalt
      catalyzed asymmetric Z-cyclopropanation of alkenes with alpha-nitrodiazoacetates.

PMID- 18825767
TI  - Opening the "stable" door.

PMID- 18825768
TI  - Ecodesign of ordered mesoporous materials obtained with switchable micellar
      assemblies.

PMID- 18825770
TI  - Template-directed assembly of zeolite-like metal-organic frameworks (ZMOFs): a
      usf-ZMOF with an unprecedented zeolite topology.

PMID- 18825769
TI  - Hydrodesulfurization of 4,6-dimethyldibenzothiophene over noble metals supported
      on mesoporous zeolites.

PMID- 18825771
TI  - Twenty-six-year-old female with assumed Crohn's disease and a gastrointestinal
      stromal tumor: Response.

PMID- 18825773
TI  - Local application of tacrolimus in distal colitis: feasible and safe.
AB  - BACKGROUND: Tacrolimus is a potent immunomodulator that is effective in the
      systemic treatment of inflammatory bowel diseases (IBD). However, potential
      toxicity and systemic (side) effects after oral intake limit its use. We
      investigated the local applicability and safety of tacrolimus for distal colitis.
      METHODS: Patients with refractory left-sided colitis or proctitis were treated
      for 4 weeks with a daily tacrolimus 2-4 mg enema or 2 mg suppository. Safety of
      local tacrolimus treatment was assessed by measurement of whole blood tacrolimus
      trough levels by monitoring liver and kidney function and blood glucose levels.
      Efficacy of treatment was assessed by comparing the disease activity index (DAI)
      in ulcerative colitis (UC) patients and endoscopic and histologic appearances
      before and after 4 weeks of treatment. RESULTS: Nineteen patients with left-sided
      colitis (n = 7) or proctitis (n = 12) were treated. Two patients with left-sided
      colitis had Crohn's disease (CD), the other 17 patients had UC. None of the
      patients developed side effects. Blood trough levels of tacrolimus were too low
      to induce systemic immune suppression. Thirteen of 19 patients (3/5 left-sided
      UC, 0/2 left-sided CD, and 10/12 proctitis) showed clinical improvement of
      disease activity after 4 weeks of local tacrolimus treatment. Moreover, a
      significant improvement of histological appearance was observed in the
      suppository-treated group. CONCLUSIONS: This study demonstrates that local
      colonic application of tacrolimus 2-4 mg daily in patients with refractory distal
      colitis is feasible, probably safe, and potentially efficacious, and therefore
      opens the need for a further, randomized trial.

PMID- 18825772
TI  - Enhanced CBir1-specific innate and adaptive immune responses in Crohn's disease.
AB  - BACKGROUND: CBir1 is a dominant antigen with a role in innate and adaptive
      immunity in mouse models of colitis and antibodies to CBir1 are associated with
      severe human Crohn's disease (CD). Our aim was to determine whether CBir1
      stimulates innate and antigen-specific T-cell responses in CD. We demonstrate
      that CBir1 enhanced IL-6 and IL-1beta production by peripheral blood (PB)
      monocytes. METHODS: Real time polymerase chain reaction (PCR) was used for
      measurement of IL6 and IL1 expression. [(3)H] thymidine was used to measure T
      cell proliferation and Elispot assay was used to measure IFNgamma production.
      RESULTS: IL-6 was significantly increased in monocytes from CD compared to
      controls and ulcerative colitis (UC). Anti-CBir1(+) patients and IL-6 was
      inversely correlated. A significant increase in CBir1-specific peripheral T-cell
      proliferation was more evident in cells from CD than controls and UC. CBir1
      induced increased numbers of IFN-gamma(+) cells in lamina propria mononuclear
      cells (LPMC) from CD compared to UC and controls. CONCLUSIONS: CBir1 induces
      enhanced peripheral innate and peripheral and mucosal antigen-specific T-cell
      responses in CD. Consistent with results from the mouse, CBir1 immune activation
      could play a role in CD.

PMID- 18825774
TI  - The rheological properties of modified microcrystalline cellulose containing high
      levels of model drugs.
AB  - The rheological properties of different types of microcrystalline cellulose (MCC)
      mixed with model drugs and water have been evaluated to identify the influence of
      sodium carboxymethylcellulose (SCMC) added to the cellulose during preparation. A
      ram extruder was used as a capillary rheometer. The mixtures consisted of 20%
      spheronizing agent (standard grade MCC or modified types with 6% or 8% of low
      viscosity grade SCMC) and 80% of ascorbic acid, ibuprofen or lactose monohydrate.
      The introduction of SCMC changed all rheological parameters assessed. It produced
      more rigid systems, requiring more stress to induce and maintain flow. Degree of
      non-Newtonian flow, angle of convergence, extensional viscosity, yield and die
      land shear stress at zero velocity, and static wall friction were increased, but
      recoverable shear and compliance were decreased. The presence of SCMC did not
      remove the influence of the type of drug. The mixture of ibuprofen and standard
      MCC had the lowest values for shear stress as a function of the rate of shear,
      extensional viscosity, and angle of convergence, but the highest values for
      recoverable shear and compliance. The findings indicate that the system has
      insufficient rigidity to form pellets.

PMID- 18825775
TI  - Comparison of prototypic cases of depressive personality disorder and dysthymic
      disorder.
AB  - Although depressive personality disorder (DPD) was included in the Diagnostic and
      Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV; American
      Psychiatric Association, 1994) appendix as a proposed category needing further
      research, there are concerns that it overlaps excessively with dysthymic disorder
      (DD). The purpose of this investigation was to identify the characteristic
      features of representative patients with DPD and patients with DD, and to
      determine whether they could be distinguished by their symptoms. Two matched
      samples of psychologists (n=57, n=48) identified a prototypic patient with DPD or
      DD, provided demographic and treatment information about the patient, and rated
      the patient's symptoms on a series of mood and personality disorder symptoms
      taken from the DSM-IV and the literature. When composite descriptions were
      constructed using the highest rated symptoms, there was considerable overlap in
      symptoms of identified DPD and DD patients. The DSM-IV research criteria for DPD
      provided the best description of the DPD patients; however, there was a high
      degree of correlation between DPD and DD criteria sets. There was also
      considerable comorbidity, with the majority of the patients in both groups
      meeting criteria for DPD and DD. However, there was a significant difference in
      comorbid diagnoses (and other differences in family history, outcome, and
      treatment history that failed to reach the more stringent level of statistical
      significance, i.e., p<.001) suggesting that there may be some important
      differences between DPD and DD. Nevertheless, the symptom ratings imply blurred
      boundaries between DPD and DD, suggesting the need for clearer differentiation
      between the two disorders or the need to adopt an alternative model of
      classification.

PMID- 18825776
TI  - CD4 and CD8 enumeration for HIV monitoring in resource-constrained settings.
AB  - BACKGROUND: We developed a volumetric single platform image cytometer (SP ICM)
      that is dedicated to count CD4(+) and CD8(+) T lymphocytes for HIV monitoring in
      resource-constrained settings. The instrument was designed to be low-cost, yet
      reliable, easy-to-use, and robust. METHODS: Whole blood is incubated with CD3
      magnetic nanoparticles, CD4-phycoerythrin (PE), and CD8-peridinin-chlorophyll
      protein complex (PerCP). The CD3 cells are immunomagnetically attracted to an
      analysis surface, where fluorescence images of CD4(+) and CD8(+) T lymphocytes
      are recorded and analyzed, respectively. We compared CD4, CD8 counts, and CD4/CD8
      ratio obtained by the SP ICM with those from a SP flow cytometer (FCM) tetraCXP
      method on blood samples from 145 patients. RESULTS: Good correlations were
      obtained (R: 0.96-0.99) between the SP ICM and the SP FCM. There was
      approximately 10% CD8 undercount in the SP ICM, which could be partly caused by
      CD8(+dim) T lymphocytes that were not detected by the instrument or not counted
      by the image analysis due to the cross-talk from the CD4-PE signal in the CD8
      PerCP image. CONCLUSIONS: The SP ICM is a good candidate for HIV monitoring in
      point-of-care settings of resource-constrained countries.

PMID- 18825777
TI  - The effect of cell fixation on the discrimination of normal and leukemia cells
      with laser tweezers Raman spectroscopy.
AB  - Laser tweezers Raman spectroscopy (LTRS) was used to characterize the effect of
      different chemical fixation procedures on the Raman spectra of normal and
      leukemia cells. Individual unfixed, paraformaldehyde-fixed, and methanol-fixed
      normal and transformed lymphocytes from three different cell lines were analyzed
      with LTRS. When compared to the spectra of unfixed cells, the fixed cell spectra
      show clear, reproducible changes in the intensity of specific Raman markers
      commonly assigned to DNA, RNA, protein, and lipid vibrations (e.g. 785, 1230,
      1305, 1660 cm(-1)) in mammalian cells, many of which are important markers that
      have been used to discriminate between normal and cancer lymphocytes. Statistical
      analyses of the Raman data and classification using principal component analysis
      and linear discriminant analysis indicate that methanol fixation induces a
      greater change in the Raman spectra than paraformaldehyde. In addition, we
      demonstrate that the spectral changes as a result of the fixation process have an
      adverse effect on the accurate Raman discrimination of the normal and cancer
      cells. The spectral artifacts created by the use of fixatives indicate that the
      method of cell preparation is an important parameter to consider when applying
      Raman spectroscopy to characterize, image, or differentiate between different
      fixed cell samples to avoid potential misinterpretation of the data.

PMID- 18825778
TI  - NMR-derived folate-bound structure of dihydrofolate reductase 1 from the
      halophile Haloferax volcanii.
AB  - Folate binds to dihydrofolate reductase (DHFR) to form a binary complex whose
      structure maintains the overall configuration of the enzyme; however, some
      significant changes are evident when a comparison is made to the enzyme. The
      structure of DHFR1 from the halophilic Halopherax volcanii was solved in its
      folate-bound form using nuclear magnetic resonance spectroscopy. NOE data
      obtained from the (15)N-NOESY-HSQC and (13)C-NOESY-HSQC experiments of the triply
      labeled ((1)H, (13)C, and (15)N) binary complex were used as input for the
      structure calculation with the Crystallography and Nuclear Magnetic Resonance
      System program. The resulting family of structures was compared with the enzyme
      solved by both nuclear magnetic resonance and X-ray crystallography and also to
      the mesophilic folate-bound enzyme from Escherichia coli. The binary complex
      exhibited less convergence of structure in the alpha2-helix and differences in
      the hinge residues D39 and A94. In comparison to the previously reported
      mesophilic binary complex solved by X-ray crystallography, the halophilic binary
      complex reported here does not agree with the convergence of the M20 loop to a
      single structure. The corresponding L21 loop of the halophilic binary complex
      family of structures solved by nuclear magnetic resonance indicates variability
      in this region.

PMID- 18825779
TI  - A rapid, fluorescence-based assay for detecting antigenic modulation of the
      acetylcholine receptor on human cell lines.
AB  - BACKGROUND: Myasthenia gravis (MG) is an autoimmune disease affecting
      approximately 40,000 patients in the United States. One of the major mechanisms
      of disease pathology in MG is the binding, internalization, and eventual
      destruction of acetylcholine receptors (AChR) at the neuromuscular junction by
      cross-linking AChR-specific autoantibodies. This process, known as antigenic
      modulation, ultimately attenuates the ability of muscle cells to contract in
      response to signals from neurons, leading to muscle weakness and fatigue. For
      this reason, antigenic modulation of the AChR on cultured cells has become an
      important diagnostic tool for assessing the pathogenicity of AChR-specific
      autoantibodies. Traditionally, these assays have been done using radiolabeled
      AChR ligands such as (125)I alpha-bungarotoxin to determine relative AChR number.
      Here, we present a high-throughput immunofluorescent flow cytometry-based assay
      that can be used to quantify AChR levels on the cell surface and assess the
      efficacy of molecules designed to rescue antigenic modulation. METHODS: AChR
      levels were quantified on human muscle cells before and after treatment with AChR
      antibodies via immunofluorescent labeling with the AChR monoclonal antibodies,
      mAb210 and mAb B3, followed by flow cytometry of EDTA-treated cells. RESULTS:
      Using a novel, flow cytometry-based assay, antigenic modulation of the AChR was
      demonstrated on human cells using both AChR-specific monoclonal antibody and MG
      patient serum. The degree of antigenic modulation was dose responsive to antibody
      levels and could be reversed by preincubating antibodies with soluble AChR alpha
      subunit extracellular domain. SUMMARY: A rapid, nonradioactive assay was
      developed to determine the potential of AChR-specific antibodies in the serum of
      MG patients to bind and down-regulate the AChR. This assay can be used to assess
      the ability of putative therapeutics that rescue antigenic modulation and could
      be developed for the treatment of MG.

PMID- 18825780
TI  - Microimaging FTIR of head and neck tumors. IV.
AB  - On continuing our studies on head and neck neoplasia, specimens from salivary
      gland tumors have been explored by using infrared microimaging spectroscopy to
      discern healthy from neoplastic tissues. Samples with Warthin tumor, epithelial
      displasia, marginal B-cell lymphoma, low-grade adenocarcinoma, and adenoid cystic
      carcinoma pathologies have been investigated by using conventional light sources.
      Changes were monitored at the molecular level, probing spectral markers such as
      Amide I and II, phosphate, nucleic acids, and carbohydrates vibrational modes. In
      all cases, supervised and unsupervised spectral analyses resulted in satisfactory
      agreement with histopathological findings.

PMID- 18825781
TI  - Chrome dome not equal to sicker ticker.

PMID- 18825782
TI  - Ask the doctor. My blood pressure is high when I first get up in the morning,
      generally around 150/80, but always drops back to normal (around 120/60) by 9
      a.m. and stays that way throughout the day. I take 150 milligrams of Avapro in
      the morning and again in the evening, along with a diuretic in the morning. I
      check my blood pressure at home using a meter that was verified in my
      cardiologist's office. My doctor says I shouldn't worry about the temporary high
      morning blood pressure. What do you think?

PMID- 18825783
TI  - I've read about dangers to our hearts from air pollution and traffic exhaust. 
      How serious concern is this?

PMID- 18825784
TI  - I'm 69 and have stable angina, but I sometimes worry that I might be having a
      heart attack that mirrors a bout of angina.  How can I distinguish one event from
      the other?

PMID- 18825785
TI  - Cataract removal.  Continued advances.

PMID- 18825786
TI  - Acupuncture and trigger point therapy for pain relief.

PMID- 18825787
TI  - Vasculitis. Blood vessel inflammation takes many forms.

PMID- 18825788
TI  - I'm considering having a laser hair removal procedure.  Do these procedures
      permanently remove unwanted hair?

PMID- 18825789
TI  - Making CPR easier may save more lives.

PMID- 18825790
TI  - Can weight-loss counseling help me keep off the pounds I just lost?

PMID- 18825791
TI  - The impact of intensive insulin protocols and restrictive blood transfusion
      strategies on glucose measurement in American Burn Association (ABA) verified
      burn centers.
AB  - The prevalence of intensive insulin and restrictive blood use protocols in burn
      centers is unknown, which may be problematic as the combined impact of these
      therapies is to concomitantly increase the prevalence of anemia and hypoglycemia
      in intensive care unit patients. Such a development is important because point-of
      care (POC) glucometers report erroneously high values in the presence of low
      hematocrit (HCT), potentially masking the presence of hypoglycemia. We
      hypothesized that most American Burn Association (ABA) verified burn centers have
      adopted intensive insulin therapy while simultaneously restricting blood
      transfusions potentially increasing risk of hypoglycemia. All ABA verified burn
      centers (N = 44) were contacted. Clinical practices regarding intensive insulin
      therapy, restrictive transfusion practices, and the use of POC glucometers were
      evaluated. Intensive insulin protocols were implemented at 73% of ABA centers
      (defined as upper glucose target of < or = 120 mg/dl) and POC glucometers
      measurement was nearly universal; 95% of ABA centers use them routinely. Anemia
      is prevalent in intensive care units and may be increasing because of recent
      changes in practice. Defined hemoglobin and HCT levels trigger blood transfusion
      at 84% of centers, and of these, 51% restrict transfusion to hemoglobin < 7 g/dl
      or HCT < 22%. Most ABA centers now use intensive insulin protocols, many in
      combination with restrictive transfusion strategies. The combination of a higher
      prevalence of hypoglycemia in the presence of near universal anemia is
      concerning, particularly given the pervasiveness of glucometer use among burn
      centers.

PMID- 18825794
TI  - Competency issues for managers.

PMID- 18825797
TI  - Fixing unfair advantages? Providers hope to see more transparency, networks with
      Medicare private fee-for-service plans in wake of veto override.
AB  - The new Medicare law delivers a raft of changes. But physicians are cheering the
      loudest for the rollback of the 10.6% reimbursement cut and the revamping of
      Medicare Advantage. "It doesn't make any sense that these private plans are paid
      17% more than traditional Medicare and don't have to share a dime with the
      hospitals or physicians," says Albert Fisk, left, a Washington state physician.

PMID- 18825798
TI  - Anemic performance. Commonwealth Fund says things are getting worse.

PMID- 18825799
TI  - Credit crunch consequences.

PMID- 18825800
TI  - Restructuring bioshield. Move aims for better organization, as hospitals
      cooperate on preparedness.

PMID- 18825801
TI  - Ascension: work to be done. System says plan prevents deaths, not all mistakes.

PMID- 18825802
TI  - A gray tsunami cometh. Long-term care is challenged by the onslaught of the baby
      boomers, but concern is muted by a lack of immediacy.

PMID- 18825803
TI  - One state's answer. Pennsylvania has taken on the challenge of change.

PMID- 18825804
TI  - Caring for military veterans--in more ways than one.

PMID- 18825805
TI  - Brachydactyly and ectodermal dysplasia--is it a new association?

PMID- 18825806
TI  - Early post-traumatic epilepsy in a patient with initial normal CT scan.

PMID- 18825807
TI  - Intestinal permeability and toxicity of second-line therapeutic agents in ovarian
      cancer.

PMID- 18825808
TI  - Healthcare holds on tight. As the markets roil and financial giants fall, experts
      say things won't be all that bad for healthcare organizations.
AB  - Investor fear stirred up by the news last week about Lehman Bros. and AIG should
      eventually subside, leaving little long-term effect on healthcare finance,
      experts say. Chris Payne, left, with healthcare financial advisory firm Ponder &
      Co., says, "I don't see any fundamental reason why this will cause a lack of
      capital to healthcare organizations".

PMID- 18825809
TI  - Bankruptcy bug hits hospitals. At least four have filed for protection in last
      month.

PMID- 18825810
TI  - Healthcare shunted aside. Economy dominates as Congress prepares for recess.

PMID- 18825811
TI  - Hoping for a clean slate. Medicare physician payment formula needs fixing.

PMID- 18825812
TI  - Delbanco tries surveillance. Former Leapfrog CEO joins monitoring firm.

PMID- 18825813
TI  - Charges pending. Virgin Islands readies case against Miller.

PMID- 18825814
TI  - Staten Island settles again. Record $88.9 million payout for individual hospital.

PMID- 18825815
TI  - Food for thought.

PMID- 18825816
TI  - Schizophrenia: a case of nature ... or nurture?

PMID- 18825817
TI  - Choose life.

PMID- 18825818
TI  - The bigger picture.

PMID- 18825819
TI  - Outside the box.

PMID- 18825820
TI  - Welfare writes.

PMID- 18825821
TI  - Getting healthier, staying healthier.

PMID- 18825822
TI  - Vocational rehabilitation: variety is the key to success.

PMID- 18825823
TI  - Beyond Bedlam.

PMID- 18825824
TI  - Getting older gracefully.

PMID- 18825825
TI  - Network.

PMID- 18825826
TI  - View point.

PMID- 18825827
TI  - Determination to narrow the gaps. Forward.

PMID- 18825828
TI  - Future goal. The human workshop.

PMID- 18825829
TI  - Evidence and action. Interviewed by Andy Cowper.

PMID- 18825830
TI  - Spearhead. Lessons in success.

PMID- 18825831
TI  - National support teams. Mirror image.

PMID- 18825833
TI  - Technology. The fortune teller.

PMID- 18825832
TI  - Infant mortality. Beating the odds.

PMID- 18825834
TI  - Partnership. Double act.

PMID- 18825835
TI  - Cancer care. Sooner the better.

PMID- 18825836
TI  - Mainstreaming. Healthy drives.

PMID- 18825837
TI  - [Fifth revolution in medicine: on the role of infections in pathogenesis of aging
      and chronic diseases].
AB  - The XXth century is marked by the substantial increase in human life expectancy.
      Historically, main reasons for that are four achievements of medicine: (1)
      improvements in common hygiene, such as waste disposal and water purification
      which led to the significant reduction of communicable diseases; (2) common
      recognition of Pasteur's Germ Theory followed by improvements in occupational and
      personal hygiene as well as introduction of antiseptic and aseptic measures; (3)
      decrease in childhood mortality due to the discovery and widespread application
      of vaccination; and (4) the discovery and clinical application of antibiotics. An
      epidemiological transition took place, i.e. the shift from communicable
      infectious diseases, as a main cause of morbidity and mortality, to chronic
      degenerative diseases, mainly considered non-infectious. Experimental evidence
      has been accumulated on a significant number of microorganisms, including viruses
      (such as a group of herpes viruses, hepatitis viruses, etc.), bacteria
      (Chlamydia, Helicobacter, periodontal pathogens, etc.), fungi and parasites, as
      an underlying reason for many of diseases, such as atherosclerosis, various
      cancers, type 1 and 2 diabetes, neurodegenerative and some psychiatric diseases,
      osteoporosis, autoimmune diseases and others. On the other hand, most of these
      diseases have been traditionally associated with age, together with other "age
      related" disorders, such as immune system suppression, thymus involution,
      pathologic calcification, etc. Taken together, these facts suggest that aging,
      among others, has infectious origins, and that burden of infections may lead to
      enhanced senescence and premature death. In fact, infections may serve as a
      trigger of senescence, presumably via the mechanisms of chronic oxidative stress,
      low-grade inflammation, telomere shortening, and autoimmune processes due to the
      molecular mimicry. We believe that next step in human longevity increase can be
      possible by common appreciation of the role of infections as the main trigger of
      age-related diseases and disorders, and by efforts to cure and/or eradicate these
      infections.

PMID- 18825838
TI  - More about LORS.

PMID- 18825839
TI  - Stimulant-associated cognitive abnormalities: mechanisms and impact on reward
      related behavior and addiction.

PMID- 18825840
TI  - The history holds the key in this gardener with a skin infection.

PMID- 18825841
TI  - Retraction notice to "The effect of quercetin, a bioflavonoid on
      ischemia/reperfusion induced renal injury in rats".

PMID- 18825842
TI  - Abstracts of the Canadian Radiosurgery Society Meeting. February 29-March 1,
      2008. Tremblant, Quebec.

PMID- 18825843
TI  - Gastrointestinal and liver physiology. Preface.

PMID- 18825844
TI  - Aberrant expression of CD7 in acute myeloid leukemias with FLT3-ITD.

PMID- 18825845
TI  - Retraction: Use of tiotropium bromide for pre-operative treatment in chronic
      obstructive pulmonary disease patients: comparison with oxitropium bromide.

PMID- 18825846
TI  - Compassionate metrics: an oxymoron in practice.

PMID- 18825847
TI  - Putting pressure on the Burmese Government.

PMID- 18825848
TI  - Choosing the right surgical glove: an overview and update.
AB  - Sterile surgical gloves are routinely worn during all invasive procedures to
      prevent the two-way transmission of pathogens between the surgical team and the
      patient. This reduces the risk of surgical-site infections and blood-borne
      diseases. Since their introduction to the operating room over 100 years ago,
      surgical gloves, and the materials used to make them, have continued to evolve in
      line with ever-changing healthcare demands. Following recent developments in
      surgical glove technologies, including de-proteinized natural rubber latex and
      newer gloving methods such as triple gloving, it is timely that an overview and
      update of surgical gloves is given. By providing information on latex-associated
      allergies, glove materials, gloving methods and glove protection, this article
      will enable practitioners to choose the most appropriate surgical glove.

PMID- 18825849
TI  - Performing a percutaneous liver biopsy in parenchymal liver diseases.
AB  - There are many ways of obtaining a liver biopsy sample but the percutaneous
      method is deemed as one of the simplest and safest methods. Percutaneous liver
      biopsy (PLB) is a commonly performed procedure carried out for the diagnosis and
      management of patients with parenchymal liver diseases. It plays a central role
      in providing histological assessment for either diagnostic or therapeutic
      purposes. This article describes how PLB is performed at the Royal Free Hospital
      radiology department, London, under ultrasound guidance, along with indications,
      contraindications, complications and advantages/disadvantages this method offers.
      Nursing implications are discussed in terms of assisting, caring and managing for
      these patients safely. This article aims to raise awareness of PLB and inform the
      reader how this tissue sample is taken, thus enabling further understanding of
      this procedure. It is concluded that the percutaneous route of obtaining a liver
      biopsy enables a good size and quality of sample to be taken in a safe and
      effective manner, with usually one pass being required with minimal associated
      complications.

PMID- 18825850
TI  - Use of a modified OSCE to assess nurse practitioner students.
AB  - Assessment of clinical competence in nurse practitioner programmes has been
      greatly advanced over the last 10 years by widespread use of the objective
      structured clinical examination (OSCE). This article describes a modified OSCE
      developed in a nurse education department at a specific university within the UK
      to standardize evaluation of the physical examination skills of nurse
      practitioner students. Stations comprise procedure stations, which require
      students to perform a 'whole' examination of the subject, and question stations,
      which are composed of two forms of viva, involving various cognitive activities.
      A number of other universities are currently using this modified OSCE as a tool
      for formative and summative assessment, as a learning resource, and to identify
      gaps and weaknesses in clinical skills.

PMID- 18825851
TI  - Dealing with death: first encounters for first-year nursing students.
AB  - End-of-life care, particularly for older people, is often sub-optimal in England,
      and the Government has introduced several initiatives to improve this care. The
      authors believe the twin frameworks of emotional labour and ethics of non
      abandonment underpin the provision of high-quality care. This article discusses a
      research project that investigated first-year nursing students' encounters with
      patient deaths. The research found that, to the student, every death in clinical
      practice is a learning experience and potentially a source of emotional distress;
      some students reported experiencing flashbacks afterwards and were developing
      avoidance behaviours. Students sometimes felt unsupported by mentors and also
      felt that sometimes dying patients and families were inadequately cared for. The
      theme of abandonment was evident in the students' stories. The authors conclude
      that there is still room for improvement in end-of-life care. Good role modelling
      and pastoral care by mentors is vital to student development. Link lecturers and
      mentors need to be alert to student distress.

PMID- 18825852
TI  - Sleep disruption experienced by surgical patients in an acute hospital.
AB  - BACKGROUND: Sleep has a common structure and pattern and is thought to be a
      restorative process. Sleep deprivation and disruption can cause a myriad of
      physical and psychological changes, which can all have an impact on health care.
      As such, sleep is recognized as being beneficial to health and an important
      aspect of nursing care. METHOD: This study used an expansion component mixed
      method design to describe the sleep experience of patients on surgical wards.
      This involved establishing the factors which disturb sleep and describing
      patients' experiences of sleep disruption. RESULTS: 17 of the 24 patients
      approached participated in the study, providing a 71% response rate.
      Environmental factors were found to be strongly correlated with sleep disruption
      with a Pearson's coefficient of +0.795. Personal factors were also found to be
      correlated with sleep disruption although, with a Pearson's coefficient of
      +0.590, not as strongly as environmental factors. DISCUSSION: This study found
      that environmental noise, pain and tension were most likely to disrupt the sleep
      of surgical patients. It has also established four recommendations to improve the
      sleep of hospital patients. LIMITATIONS: This study has some limitations that
      need to be considered: limited database access, a small sample size and a data
      collection tool which had not previously been tested for validity or reliability.
      CONCLUSION: This study produced some compelling findings. It is recommended,
      however, that these findings be tested by larger studies using simple random
      sampling and in-depth interviews.

PMID- 18825853
TI  - The art of auscultation: evaluating a patient's respiratory pathology.
AB  - This article considers national policy drivers promoting the development of
      advanced assessment skills and practical procedures for the safe and effective
      use of the stethoscope in the clinical area. The evidence base underpinning
      effective use of the stethoscope in clinical practice is explored, including the
      preparation of the patient and the environment, applying infection control
      policies, and placing an emphasis on privacy and dignity. This is followed by a
      practical guide to auscultation technique of the respiratory system for nurses
      developing advanced practice skills.

PMID- 18825854
TI  - Preventing venous thromboembolism through risk assessment approaches.
AB  - Venous thromboembolism (VTE) is a significant cause of morbidity and mortality in
      hospitalized patients. Recent guidelines from the Department of Health and the
      National Institute for Health and Clinical Excellence recommend mandatory,
      universal VTE risk assessment for hospitalized patients and the provision of
      appropriate prevention measures (thromboprophylaxis). Careful selection of a
      suitable VTE risk assessment approach is required to improve the chance of its
      successful implementation in hospital. At-risk patients need to be identified,
      counselled and the most appropriate thromboprophylaxis selected, prescribed and
      delivered. Nurses are ideally placed to play a central role in the implementation
      of this change in clinical practice through leadership and education. Extended
      pharmacological thromboprophylaxis has been recommended in certain high-risk
      groups. New oral anticoagulants are being evaluated, which could change the way
      thromboprophylaxis is administered in future, benefiting both patients and
      nurses.

PMID- 18825855
TI  - Professional regulation in nursing. Part 2: Political change.
AB  - The current Government came to power in 1997. In their manifesto, changes in
      ideology towards the provision of health and the place of those who provided
      health care were evident. As well as the issue of acceptable standards of
      healthcare provision, the issue of the regulation of nurses and other health
      workers was perused. This article reviews the political manifestos of 1997 and
      2001, and reflects on the changes averred to in the context of the effects to the
      nursing profession in respect of professional regulation and central control by
      the Government of the profession as a whole. A conclusion is reached that
      political changes, not based on theoretical models of care, but rather on reports
      commissioned by Government, have resulted in far reaching consequences for
      nursing. This includes the replacement of the regulatory body (United Kingdom
      Central Council for Nursing, Midwifery and Health Visiting) with a new body
      (Nursing and Midwifery Council) and the inclusion of public persons into the
      management of nurses to the extent that for the first time, lay persons would
      have an influence in the outcomes of professional disciplinary hearings and
      sanctions.

PMID- 18825856
TI  - Infant hospitalization and breastfeeding post-caesarean section.
AB  - BACKGROUND: Breastfeeding has been shown to protect infants from illness, but
      there is minimal published research on the relationship between illness and
      breastfeeding following caesarean delivery. AIM: To examine the association
      between post-caesarean breastfeeding and infant hospitalization in the first year
      of life. STUDY DESIGN AND METHODS: A retrospective cohort study of 468 term
      infants examined the relationship between infant hospitalizations and
      breastfeeding, using hospital admissions records and surveys from a post
      caesarean breastfeeding intervention study in an Israeli hospital. RESULTS: A
      significantly lower proportion of Jewish infants breastfed for at least 4 months
      (40%; 42) was hospitalized in the first year, compared with non-breastfed infants
      (60%; 62) (P = 0.003). Among the Muslim infants who were breastfed, a
      significantly lower proportion were hospitalized (33%; 35) than those who were
      not hospitalized (67%; 71) and a greater proportion of non-breastfed infants were
      hospitalized (80%; 8) than those who were not hospitalized (20%; 2) (P = 0.005,
      Fisher's exact test). In the logistic regression models, the significant
      variables decreasing the likelihood of hospitalization for Jewish infants were
      being born to a non-immigrant mother, higher maternal education, and being
      breastfed, and for Muslim infants the only significant variable was being
      breastfed. CLINICAL IMPLICATIONS: Breastfeeding in post-caesarean women has a
      protective effect on infant health, as demonstrated by a decrease in illness
      related hospitalizations in the first year of life.

PMID- 18825857
TI  - Skin integrity and silicone: Appeel 'no-sting' medical adhesive remover.
AB  - This article offers an overview of skin and the importance of maintaining intact
      skin in relation to wound and stoma care. Various patients and their conditions
      are considered in relation to their potential for skin damage with the removal of
      adhesive products, including paediatrics, those with epidermolysis bullosa,
      haemangioma, fragile skin, elderly skin and ostomates. The importance of
      protecting fragile skin and protecting the peri-wound and peri-stoma area is
      discussed and the impact of such damage on quality of life is considered. The
      evidence relating to the impact that silicone-based adhesive removers can have is
      reviewed with a conclusion that an evidence-based approach can significantly
      affect patient outcomes.

PMID- 18825858
TI  - The spiritual state we're in: the role of parish nursing.

PMID- 18825859
TI  - Health care issues among lesbian, gay, bisexual, transgender and intersex (LGBTI)
      populations in the United States: Introduction.
AB  - This supplemental issue of the Journal of Homosexuality presents research that
      explores a variety of health care issues encountered by lesbian, gay, bisexual,
      transgender and intersex (LGBTI) population groups in the United States over the
      10-year period from 1993 to 2002. Topics include access to health care,
      utilization of care, training of medical and mental health providers, and the
      appropriate preparation of clinical offices and waiting areas. Authors used a
      variety of community-based public health research methods, including participant
      and provider surveys and retrospective chart reviews of patients, to develop this
      body of research, providing a recent-historical perspective on the complex health
      care and health-related needs of sexual and gender minorities. Particularly for
      transgender and intersex populations, the state of research describing their
      health care needs is in its infancy, and much remains to be done to design
      effective medical and mental health programs and interventions.

PMID- 18825860
TI  - Caring for vulnerable populations: curricula in U.S. internal medicine
      residencies.
AB  - The Accreditation Council for Graduate Medical Education (ACGME) encourages
      internal medicine training programs to include specific curricula devoted to
      health care issues of vulnerable populations. Our aim was to determine the
      prevalence of curricula involving selected vulnerable populations among U.S.
      Internal Medicine residencies. We conducted a survey of Program Directors of all
      US Internal Medicine Residencies assessing whether the program had a curriculum
      for six vulnerable populations (racial and ethnic minorities, non-English
      speaking patients, lesbians, gay men, victims of domestic violence and patients
      with substance abuse problems). Most residencies address substance abuse and
      victims of domestic violence, while there remains a lack of dedicated teaching on
      other vulnerable populations, including lesbians, gay men, racial and ethnic
      minorities and non-English speaking patients.

PMID- 18825861
TI  - Intersex mental health and social support options in pediatric endocrinology
      training programs.
AB  - The birth of a child with an intersex condition is often an emotionally stressful
      event for parents. Preparation and ongoing support systems could be beneficial to
      both parents and children and would alleviate some of the shame and isolation
      associated with intersex conditions. To assess the extent to which psychological
      support is available, a short e-mail survey on this topic was sent to the
      directors of 50 pediatric endocrinology fellowship training programs (PEFTPs),
      who are most likely to evaluate and treat intersex children and their parents. Of
      the 29 PEFTPs that responded, 69% offer psychological support and 58% have a
      mental health specialist on staff. However, only 19% of patients or families
      receive emotional support during diagnosis and only 15% receive support after
      diagnosis. We found two barriers that prevent patients and families from
      receiving psychological help from their intersex care team. First, there is a
      lack of training for mental health professionals regarding the needs of intersex
      patients and families. Second, some families refuse help even though it is
      offered. This study reveals that further research is needed to overcome these two
      barriers regarding mental health treatment of intersex patients and families.

PMID- 18825862
TI  - Utilization of health care among female-to-male transgender individuals in the
      United States.
AB  - Female-To-Male (FTM) transgender individuals were approached at a conference and
      several peer support groups in the United States and asked to complete a short
      questionnaire regarding their medical care. Results from the 122 completed
      questionnaires indicated that a high number of respondents were taking
      testosterone (n = 106) and had some gender-confirming surgery (n = 68). Seventy
      percent of respondents rated their overall quality of health care "good" or
      "excellent." A surprising finding was the low number (7%) reporting diagnoses of
      polycystic ovarian syndrome--the incidence of which has been reported elsewhere
      as high as 50%. Also notable were the high levels of employment, insurance,
      knowledge of standards of care, and access to providers, contrasting with reports
      from studies involving predominantly Male-To-Female (MTF) individuals. Finally,
      FTM's usage of transition-related medical resources can vary, but many within
      this study are foregoing genital surgery.

PMID- 18825863
TI  - Sexual orientation and sexual health care needs: a comparison of women
      beneficiaries in outpatient military health care settings.
AB  - The objectives of this study are to compare the sexual concerns, interest and
      experiences in discussing these concerns with their doctor for women of "Only
      Men" and "Some to Only Women" sexual orientation. A survey was mailed to women
      patients from two military outpatient settings, with 1,196 women responding. Of
      eligible respondents (N = 1,170), 90% reported "Only Men" and 10% reported "Some
      to Only Women" sexual orientation. Sexual concerns varied by sexual orientation,
      while interest and experience in discussing sexual concerns and desire for
      physicians to initiate the topic differed minimally. Women with "Some to Only
      Women" sexual orientation have both similar and differing sexual concerns
      compared to "male-only" oriented women. Larger primary care patient-based studies
      of sexual health care needs of sexual minorities are needed.

PMID- 18825864
TI  - Active duty military personnel presenting for care at a Gay Men's Health Clinic.
AB  - Under the "Don't Ask, Don't Tell, Don't Pursue, Don't Harass" Department of
      Defense policy, gay men and women are allowed to serve in the military, but they
      are not allowed to disclose their sexual orientation. This study was performed to
      determine the incidence of active duty military personnel seeking care at a Gay
      Men's Health Clinic. Nine percent of the clients, who had served between June and
      August 2002, were active duty U.S. Navy sailors. They all expressed fears of
      being discharged from the military when asked why they did not access military
      healthcare. The "DADTDPDH" policy breeds distrust between men who have sex with
      men (MSM) service-members and their healthcare provider and this ensures
      inadequate healthcare.

PMID- 18825865
TI  - A clinical comparison of lesbian and heterosexual women in a psychiatric
      outpatient clinic.
AB  - Previous research has reported that when compared to heterosexual women, lesbians
      may use alcohol and illicit substances to a greater degree and may experience
      greater psychiatric symptomatology. This study sought to describe any differences
      in clinical diagnoses, familial histories, and substance usage between lesbian
      and heterosexual women in a psychiatric outpatient clinic. A chart review was
      conducted and a sample of 455 heterosexuals and 75 lesbians was obtained. Data,
      where available, included demographic information, clinical diagnoses, time in
      treatment, sexual orientation, past and present substance use, and familial
      substance abuse and psychiatric history. Lesbians were found to have greater past
      illicit substance use but less current use. No significant differences were found
      for alcohol use. Similarly, no significant differences in clinical diagnoses were
      found. Significant differences were found among families. Family members of
      lesbians had greater substance use and psychiatric histories. These findings both
      support and dispute some previous research and suggest areas for future
      researchers to explore.

PMID- 18825866
TI  - Mental health concerns of gay and bisexual men seeking mental health services.
AB  - Little data exist about the mental health needs of gay and bisexual men. This is
      due to limitations of existing studies such as small and nonrepresentative
      samples, failure to assess sexual orientation, and concerns about stigmatization,
      possibly causing sexual minority individuals to be reluctant to disclose their
      sexual orientation to researchers. Fenway Community Health is a large urban
      health center that serves the LGBT community. The large number of gay and
      bisexual men who present for mental health treatment allows for a unique
      opportunity to gain insight into mental health, prevention, and intervention
      needs for this group. The current study is a review of the mental health
      information from all of the gay and bisexual men who reported that they were HIV
      negative during their mental health intake over a six-month period at Fenway
      Community Health (January to June 2000; N = 92). The most frequent presenting
      problems were depression, anxiety, and relationship issues. Additionally,
      presenting problems included current or past abuse, substance abuse, finance and
      employment, recent loss, and family issues. The most frequent diagnoses were
      depression, anxiety disorders, and adjustment disorders. These findings support
      the notion that presenting problems and mental health concerns among gay and
      bisexual men are similar to those frequently reported by individuals in other
      mental health facilities, however, specific psychosocial stressors are unique to
      this population.

PMID- 18825867
TI  - HIV testing among lesbian women: social contexts and subjective meanings.
AB  - This study provides descriptive statistics on prevalence of testing, testing
      sites, and reasons for testing among lesbian women in the United States. It also
      provides qualitative data about the social meanings and specific circumstances of
      their HIV testing experiences. Analysis draws on a sample of lesbian women living
      in a single large southeastern city. An especially diverse snowball and chain
      referral sample of 162 lesbian women was given a questionnaire, and qualitative
      data were gathered from 24 women participating in three focus groups and from 67
      women participating in depth-interviews. A large majority of women in the survey
      sample (80%) reported at least one test, and more than one in four women were
      tested five or more times. More than one in ten were tested during drug treatment
      or while incarcerated. The most common testing sites were clinics and hospitals,
      and the most common reason women gave was because they "thought they were at
      risk." Most tests were voluntary rather than mandatory occupational or
      institutional requirements. The subjective meanings associated with HIV testing,
      as well as the women's counseling needs before, during, and after testing are
      analyzed. The implications for a better understanding of lesbian women's sexual
      health are discussed.

PMID- 18825868
TI  - The potential impact of discrimination fears of older gays, lesbians, bisexuals
      and transgender individuals living in small- to moderate-sized cities on long
      term health care.
AB  - As an exploration of the potential impact of fears of discrimination against
      GLBTs in long-term health care settings, this study compared perceptions of GLBT
      persons and heterosexuals. A total of 132 GLBT persons and 187 heterosexuals
      living in Eastern Washington completed a survey that contained demographic
      questions and perceptions of discrimination in long-term care settings. Most
      respondents suspected that staff and residents of care facilities discriminate
      against GLBTs. GLBT respondents who believed that residents of care facilities
      are victims of discrimination were more likely to believe that they would have to
      hide their sexual orientation if admitted to a care facility. GLBT respondents
      were more likely than heterosexual respondents to believe that GLBTs do not have
      equal access to health care and social services, that GLBTs residents of care
      facilities are victims of discrimination, that GLBT sensitivity training programs
      would benefit staff and residents of care facilities, and that GLBT retirement
      facilities would be a positive development for older GLBTs. This study is offered
      as a preliminary investigation of concerns about GLBT discrimination in health
      care settings, how concerns are expressed, and the implications of those concerns
      for health care needs.

PMID- 18825869
TI  - Medical Moneyball: a model for academic pediatric growth.

PMID- 18825870
TI  - Public policy to prevent childhood obesity, and the role of pediatric
      endocrinologists.
AB  - Childhood overweight and obesity prevalence rates in the United States are
      steadily increasing. Public health experts consider a host of overarching and
      powerful influences beyond any one person's control to be the pivotal causes of
      childhood obesity. Consequently, it is more useful from a prevention and policy
      standpoint to examine the increasingly 'toxic environments' in which we live,
      consider a comprehensive strategy, and introduce, implement, and enforce public
      health policy to change those environments. In this paper we give an overview of
      different types of public policies that have been proposed as pieces of the
      complex solution to the growing problem of childhood obesity. We review some of
      the strategies needed, and the barriers to overcome, in order to pass effective
      policy, and discuss the important role pediatric endocrinologists can play in the
      fight to win effective policy campaigns to reverse the epidemic of childhood
      obesity.

PMID- 18825871
TI  - Growth hormone in cystic fibrosis.

PMID- 18825872
TI  - Study of glucose profiles with continuous glucose monitoring in adolescents with
      poorly controlled type 2 diabetes mellitus.
AB  - AIM: To evaluate glycemic excursions in adolescents with poorly controlled type 2
      diabetes mellitus (DM2). METHODS: Seventeen adolescents (12 F/5 M) underwent
      glucose monitoring for 3 days using a continuous glucose monitoring system
      (CGMS). Glucose measurements were divided into periods of euglycemia,
      hyperglycemia, and hypoglycemia. The percentage of each period, average glucose
      concentration per 24 h, day and night, the number of excursions, and area under
      the curve (AUC) of glucose >150 mg/dl and <70 mg/dl were calculated. RESULTS: On
      average, patients remained in euglycemia for 28.5%, hyperglycemia for 70%, and
      hypoglycemia 1.3% of the total day. Hyperglycemic excursions were more frequent
      during the day. Hypoglycemic events were more frequent during the night. 24-h
      average glucose, duration of glucose >150 mg/dl, and AUC >150 mg/dl correlate
      with HbA1c and fructosamine to varying degrees. CONCLUSION: Continuous glucose
      monitoring provide valuable information on glucose excursions in adolescents with
      poorly controlled DM2 and may be helpful in improving metabolic control of poorly
      controlled adolescents with DM2.

PMID- 18825873
TI  - Determinants of plasma adiponectin levels in obese children.
AB  - Adiponectin is an insulin-sensitizing adipocytokine, and recently it has been
      suggested as a biomarker of metabolic syndrome. We studied the relationships
      between adiponectin and parameters of metabolic syndrome in obese children.
      Fasting plasma adiponectin, insulin, glucose, lipids, and anthropometric
      parameters were measured in 180 obese children and 125 non-obese controls.
      Adiponectin was significantly decreased in obese boys and girls compared to non
      obese controls. Adiponectin was inversely related to body mass index, waist
      circumference (WC), insulin, homeostasis model assessment for insulin resistance,
      and triglycerides, after adjusting for age in both genders. Adiponectin was
      correlated with high-density lipoprotein cholesterol (HDL-C) after adjusting for
      age in both genders. In multiple regression analysis, WC was independently
      related to adiponectin in boys, and WC and HDL-C were independently related to
      adiponectin in girls. In conclusion, WC, a simple measure of central adiposity,
      is a determinant of adiponectin in obese children.

PMID- 18825874
TI  - Evaluation of diagnosis and treatment results in children with Graves' disease
      with emphasis on the pubertal status of patients.
AB  - This retrospective study evaluated the clinical and laboratory characteristics at
      presentation and treatment results of patients with Graves' disease (GD) with
      respect to pubertal status. Records of 143 patients (108 F, 35 M) were reviewed
      in a multicenter study. At diagnosis, 38% of patients were prepubertal. Anti
      thyroid drugs (ATD) were used as initial therapy. There was no significant
      difference in clinical and laboratory characteristics at diagnosis, during
      treatment and adverse reaction to ATD with respect to pubertal status. Twenty
      patients (7 prepubertal, 13 pubertal) reached remission on ATD. Surgery was
      performed in seven and radioiodine (RAI) in four patients. Duration of treatment
      needed to achieve remission was longer in prepubertal (4.2 +/- 1.0 yr) than in
      pubertal patients (3.1 +/- 1.3 yr) (p = 0.02). The rate of remission was not
      different between prepubertal (25.9%) and pubertal patients (33.3%) (p = 0.59).
      ATD were associated with low remission rate in pediatric GD and required longer
      duration of therapy in prepubertal patients. For definitive treatment in older
      children, RAI could be evaluated as the initial therapy.

PMID- 18825875
TI  - Differential presentation for children with autoimmune thyroiditis discovered
      because of symptom development or screening.
AB  - AIM: To determine clinical and laboratory differences at presentation of
      autoimmune thyroiditis (AIT) among children with AIT discovered due to symptom
      development and those discovered by screening due to having increased risk of AIT
      from an underlying disorder. STUDY DESIGN: Retrospective chart review of patients
      with AIT seen in an academic pediatric endocrinology practice. We identified 252
      children with AIT: 160 diagnosed following symptom development (the 'symptoms'
      group), 74 with AIT found by screening (the 'screening' group) and 18 with
      increased risk who were tested because they developed symptoms (the 'symptoms +
      screening' group). RESULTS: We found that compared to the 'symptoms' group,
      individuals in the 'screening' group were younger and had a lower proportion of
      females. In addition, the 'screening' group were more likely to be euthyroid (60%
      of 'screening' vs 19% for 'symptoms') and less likely to have overt
      hypothyroidism (7% 'screening' vs 45% 'symptoms'). The 'screening' group were
      also less likely to have multiple symptoms of hypothyroidism noted in retrospect.
      CONCLUSIONS: Screening for AIT identifies patients at an earlier stage of AIT.
      Additionally, the association of symptoms with subclinical hypothyroidism may
      lend support to initiating levothyroxine treatment for symptomatic children with
      mild TSH elevations.

PMID- 18825876
TI  - Effect of inspiration/expiration on height measurement.
AB  - BACKGROUND: Growth parameters are a powerful screening tool in pediatric care.
      Accuracy assumes differing importance in different clinical settings. A small
      error is not clinically significant when height is obtained as a screening tool
      during annual well child visits. However, when assessing annual growth velocity
      using shorter interval visits, an error of equal magnitude might influence
      further management decisions. AIM AND HYPOTHESIS: To explore the effect of
      inspiration or expiration on height measurement. Our hypothesis was that height
      measurements obtained in inspiration would be greater than those obtained in
      expiration or without specific instructions as to status of respiration
      (unspecified). METHODS: Heights of 99 individuals 8 years and older were measured
      in inspiration, expiration and unspecified respiratory status by two pediatric
      endocrinologists. Patients were measured three times in each mode. The p values
      were adjusted by Tukey procedure for multiple comparisons among three modes.
      RESULTS: Height measurement performed in inspiration, expiration or without
      specific instruction as to breathing (unspecified) did affect height measurement.
      Mean difference +/- SEM (95% CI) between height obtained in inspiration and
      expiration was 0.22 +/- 0.03 cm (95% CI: 0.15, 0.29); between inspiration and
      unspecified 0.31 +/- 0.04 cm (95% CI: 0.22, 0.40); and between expiration and
      unspecified 0.092 +/- 0.03 cm (95% CI: 0.03, 0.16). CONCLUSIONS: Based on these
      results, we recommend multiple height measurements using uniform technique
      including inspiratory/expiratory status, especially when calculating 'annualized'
      height velocity over short intervals.

PMID- 18825878
TI  - Identification of frequency and distribution of the nine most frequent mutations
      among patients with 21-hydroxylase deficiency in Turkey.
AB  - Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders
      mainly due to defects in the steroid 21-hydroxylase (CYP21A2) gene. METHODS: To
      determine the mutational spectrum in the Turkish population, the CYP21A2 active
      gene was analyzed in 100 unrelated patients with the classical form of 21
      hydroxylase deficiency using PCR and RFLP. RESULTS: Mutations were detected in 78
      patients: 64 patients were homozygous for one mutation, seven patients were
      compound heterozygous with different mutations on each chromosome, two patients
      were homozygous for two different mutations, five patients were heterozygous, and
      22 patients harbored none of the tested mutations. The most frequent mutation was
      IVS2-13A/C (28.5%), followed by large gene deletion (17%), Q318X (11.5%), I172N
      (4%), V281L (3.5%), R356W (3.5%), 8-bp (3%), complex alleles (2%), P30L (1%) and
      E6 cluster (1%). CONCLUSION: The distribution of mutation frequencies in our
      study was slightly different from those previously reported in Turkey and in
      other parts of the world.

PMID- 18825877
TI  - Body image in adolescents with disorders of steroidogenesis.
AB  - AIM: Little is known about body image in children with endocrine conditions. We
      evaluated body image in children with congenital adrenal hyperplasia (CAH),
      familial male precocious puberty (FMPP), and Cushing's syndrome (CS). STUDY
      DESIGN: We compared 67 patients (41 CAH, 12 FMPP, 14 CS) age 8-18 years with 55
      age-matched controls. RESULTS: Patients expressed more weight unhappiness than
      controls (females: p < 0.001; males: p = 0.01). This difference remained for
      females after adjusting for body mass index (BMI) (p = 0.03), but not for males
      (p = 0.12). Unhappiness with height and age of appearance was similar between
      groups. In female patients, higher BMI was a significant predictor of weight
      unhappiness (p = 0.01). CONCLUSION: Adolescents with CAH, FMPP, and CS are at
      risk for negative body image regarding weight, but not height or age of
      appearance. Weight unhappiness is partially related to greater weight, but
      factors unrelated to physical findings seem to contribute to negative body image
      in female patients.

PMID- 18825879
TI  - Growth in familial mediterranean fever: effect of attack rate, genotype and
      colchicine treatment.
AB  - We evaluated the effect of attack frequency, homozygosity for the M694V mutation
      and colchicine treatment on growth in children with familial Mediterranean fever
      (FMF). Prepubertal patients with FMF (19 M, 14 F) were evaluated retrospectively
      for height SDS, weight SDS and body mass index (BMI) before and after 46.2 +/-
      39.8 months of colchicine therapy. Pretreatment attack frequency and acute phase
      markers at diagnosis were also recorded. While acute phase markers were not
      correlated to anthropometric variables, attack rate was negatively, albeit
      insignificantly, correlated to height and weight SDS. Height SDS did not change,
      while BMI showed a slight but significant increase during colchicine therapy
      (16.2 +/- 2.6 to 17.3 +/- 3.1 kg/m2, p = 0.035). Homozygosity for M694V did not
      affect time from the onset of symptoms to diagnosis, anthropometric variables and
      acute phase markers. In conclusion, pre-treatment attack rate and anthropometric
      development correlated negatively. Colchicine therapy improved BMI slightly, but
      significantly. Homozygosity for M694V had no effect on anthropometric
      development.

PMID- 18825880
TI  - Growth hormone therapy improves growth in children with cystic fibrosis related
      liver disease.
AB  - Growth impairment in cystic fibrosis (CF) is worsened by liver disease. Children
      with CF have serum levels of insulin-like growth factor-I (IGF-I) that are lower
      than expected for their normal growth hormone (GH) production. In children with
      CF-related liver disease (CFLD), response to endogenous GH is further reduced. We
      present our experience with two young children with CFLD given recombinant human
      GH (rhGH). The first patient was a 5 year-old female with CFLD and poor growth
      who responded well for 1 1/2 years to rhGH therapy during her initial course and
      without a significant increase in serum IGF-I, but with a substantial increase in
      IGF-I concentration when the GH dose was increased. The second patient was a 5
      month-old male with advanced liver disease who had transient improved growth and
      liver function following rhGH. These patients suggest that rhGH is safe and may
      be effective in children with CFLD.

PMID- 18825881
TI  - Isolated adrenocorticotropic hormone deficiency presenting as an acute neurologic
      emergency in a peripubertal girl.
AB  - Isolated adrenocorticotropic hormone (ACTH) deficiency (IAD) is extraordinarily
      rare, and the clinical manifestations of its accompanying adrenal insufficiency
      are diverse. Early-onset forms of IAD have been linked to mutations in the Tpit
      transcription factor gene TPIT; however, the genetic basis of juvenile- or late
      onset IAD is unknown. Herein, we describe a case of a peripubertal girl with IAD
      and a normal TPIT gene who presented with an acute neurologic emergency,
      demonstrating both the variable clinical presentation of IAD and the need for
      continued investigation into the molecular mechanisms underlying juvenile- and
      late-onset IAD.

PMID- 18825882
TI  - Non-islet-cell tumor hypoglycemia and lactic acidosis in a child with congenital
      HIV and Burkitt's lymphoma.
AB  - BACKGROUND: Non-islet-cell tumor hypoglycemia (NICTH) is a rare cause of
      hypoglycemia associated with tumors of mesenchymal, epithelial, or hematopoietic
      origin. Lactic acidosis is likewise an uncommon complication of hematological
      malignancy associated mainly with leukemia and lymphoma. Most cases of NICTH and
      lactic acidosis have been described in the adult population. We report a child
      with congenital HIV and AIDS who developed Burkitt's lymphoma, lactic acidosis
      and NICTH. PATIENT: An 11 year-old boy with AIDS, cerebral palsy and seizure
      disorder presented with intractable hypoglycemia 12 days after diagnosis of
      Burkitt's lymphoma. He had persistent hypoglycemia (serum glucose 20-40 mg/dl;
      1.1-2.2 mmo/l) despite glucose infusion rate of 6 mg/kg/minute and trial of
      diazoxide treatment. Critical sample obtained at time of hypoglycemia showed
      insulin at 1.78 microU/ml (normal <5 microU/ml), pro-insulin 5.6 pmol/l (<18.8
      pmol/l), IGF-I <25 ng/ml (80-723 ng/ml), IGF-II 422 ng/ml (610-1,217 ng/ml),
      lactate 15.6 mmol/l (normal: 0.5-2.2 mmol/l), cortisol 21 microg/dl (580 nmol/l;
      normal >10 microg/dl; 276 nmol/l), and negative insulin antibodies. He remained
      alert and seizure free despite profound hypoglycemia. A 1 mg glucagon stimulation
      test showed a rise in serum glucose of 29 mg/dl (>1.6 mmol/l). Continuous
      glucagon infusion at 0.15-0.3 mg/h maintained euglycemia until the time of his
      demise (1 month after admission) due to complications of his underlying illness.
      CONCLUSION: We present a case of lactic acidosis and NICTH in an 11 year-old boy
      with AIDS and Burkitts's lymphoma. We review the mechanism of hyperlacticacidemia
      in supporting cerebral function during profound hypoglycemia. NICTH and lactic
      acidosis in association with malignancy carries a poor prognosis. In this
      patient, continuous glucagon infusion was a successful alternative to
      corticosteroid treatment in maintaining euglycemia.

PMID- 18825883
TI  - Three years follow-up of pamidronate therapy in two brothers with osteoporosis
      pseudoglioma syndrome (OPPG) carrying an LRP5 mutation.
AB  - Osteoporosis-pseudoglioma (OPPG) is a rare syndrome characterized by severe
      osteoporosis and ocular defects caused by homozygotic inactivation mutations in
      the LRP5 gene. Bisphosphonate has been demonstrated to improve bone mineral
      density (BMD) in children with OPPG. We present here a 3 years follow-up of two
      brothers with OPPG carrying a novel mutation in the LRP5 gene, who were treated
      with intravenous pamidronate. PATIENT REPORT: We looked for a mutation in the
      LRP5 gene in two brothers (12 and 4 years old) with clinical features of OPPG
      (blindness, low BMD and fragility fractures) and in their consanguineous parents
      to confirm the diagnosis of OPPG. The patients were treated with bisphosphonate
      for 3 years. They received 1 mg/kg/day of pamidronate for 2 consecutive days,
      every 3 months during the first year, and every 4 months in subsequent years.
      Calcium, phosphorus, total alkaline phosphatase, parathyroid hormone, hepatic
      transaminases, creatinine and hemogram tests were performed before each infusion.
      Bone densitometry was performed at baseline and at the end of the follow-up.
      RESULTS AND CONCLUSION: The affected brothers carry a missense mutation in the
      third codon of exon 8 (AAT-->ATT) that led to the exchange of an asparagine for
      an isoleucine (N531I). Both parents were found to be heterozygous for this
      mutation. The intravenous pamidronate therapy was safe for up to 3 years of use.
      Moreover, increased BMD and decreased fracture rate were observed in our patients
      with OPPG.

PMID- 18825884
TI  - [Regional lymph nodes at a distance].
AB  - In 3 patients, two men aged 22 years and 38 years with melanoma, and one woman
      aged 46 years with breast cancer, local tumour growth recurred following regional
      lymph node dissection. All three developed metastasis in new distant regional
      basins, which were once more dissected. The first melanoma patient died from
      haematogenous metastasis, 2 years after the excision of his primary melanoma. The
      other melanoma patient was alive, without evidence of disease, 8 years after the
      treatment of his primary tumour. The breast cancer patient, who underwent
      contralateral axillary lymph node dissection, was also alive, without evidence of
      disease, 27 years after the treatment of her primary tumour. Diversion of
      lymphatic flow as a result of regional lymph node dissection for cancer may lead
      to metastasis to a distant lymph node basin if tumour growth recurs in the
      original area. Knowledge of this usually unknown phenomenon is important since
      metastasis to these new regional basins can still be treated curatively, in the
      form of another lymph node dissection. These distant lymph node basins must
      therefore be carefully checked during follow-up monitoring.

PMID- 18825885
TI  - [Insufficient basis for the inclusion of Human papillomavirus vaccination in the
      National Immunisation Programme in The Netherlands].
AB  - The Dutch Minister of Health, Welfare and Sportintends to implement Human
      papillomavirus (HPV) vaccination for 12-year-old girls and catch-up vaccination
      for 13- 16-year-old girls, as part of the National Immunisation Programme from
      September 2009 onwards. However, due to a well-organised screening programme,
      cervical cancer is not an important public health problem in the Netherlands any
      more, which limits the possible impact of HPV vaccination. Vaccine trials thus
      far have involved a relatively small number ofparticipants with limited follow
      up, so the efficacy of the vaccine in preventing cervical cancer is not yet
      known. There are no data on frequency and severity of possible adverse events and
      the vaccine has not yet been tested in the intention-to-vaccinate group of 12
      year-old girls. Even when we assume that HPV16/18-related cervical cancer is
      prevented on a lifelong basis, the cost-effectiveness ratio of HPV vaccination is
      estimated not to be favourable. In conclusion, HPV vaccination does not seem to
      be urgent in the Netherlands. Therefore we advise studying the safety in 12-year
      old girls first while at the same time waiting for the longer follow-up results
      of ongoing trials.

PMID- 18825886
TI  - [Secondary breast operations are often necessary and are no indication of poor
      oncological quality].
AB  - The most important factor for tumour recurrence after breast-saving surgery is
      the margin status. In the Netherlands a 1-mm free margin has been formulated as
      sufficient, and totally free margins are not necessary in all cases. The current
      Dutch Health Inspectorate performance indicator, i.e. 10% reexcisions allowed to
      achieve free margins, is a performance indicator of questionable validity. As
      long as there is worldwide discussion about the ideal margin in breast-saving
      surgery a specific norm cannot not be dictated. The aim of the discussion should
      be how to prevent local recurrence. This percentage is the real performance
      indicator.

PMID- 18825887
TI  - [Telephone accessibility of Dutch general practices: improvements can be made,
      but will not fully solve the problem].
AB  - The Dutch Health Inspectorate published a research report on the accessibility by
      telephone of Dutch general practices. A large proportion of Dutch GPs have not
      organized their practices according to standard norms as far as accessibility by
      telephone is concerned. Several developments can explain this substandard
      accessibility, such as an increasing number of telephone calls and changes in
      staff practice routine. Technical solutions such as voice response systems or
      more incoming lines cannot resolve all the problems. More information on the
      accessibility for patients, smarter systems for repeat prescriptions and the use
      of email could improve the situation. The development of best practices and
      research into the efficacy of the proposed solutions is necessary.

PMID- 18825888
TI  - [Fish fatty acids and cardiovascular diseases--an update].
AB  - Epidemiologic observational research shows that higher intake of fish fatty acids
      is associated with a lower risk of fatal heart disease and sudden death, but this
      effect is not observed with non-fatal heart disease. Currently available trials
      with clinical endpoints provide no convincing evidence that supplementation with
      fish oil prevents cardiovascular disease. The theory that fish fatty acids can
      prevent cardiac arrhythmias is not supported by the trials performed in patients
      with life-threatening cardiac arrhythmias. For the specific group of patients who
      have previously experienced a ventricular tachycardia and who have not been
      prescribed an anti-arrhythmia medication for this, there are indications that the
      intake of fish oil might even lead to a slightly increased risk ofsevere cardiac
      arrhythmias. However, other subgroups of patients, such as patients with a recent
      myocardial infarction may benefit from taking fish oil to prevent cardiac
      arrhythmias. The advice of the Health Council of the Netherlands to eat fish
      twice per week, of which fatty fish once per week, or to take 450 mg of the
      combination eicosapentaenic acid (EPA) and docosahexaenic acid (DHA) per day
      remains justifiable until the results from current studies become available.
      However, patients with a ventricular arrhythmia who do not receive specific anti
      arrhythmic medication should be careful about taking fish oil capsules.

PMID- 18825889
TI  - [Diagnostic image (389). A woman with a multicystic vulvar mass].
AB  - A 28-year-old woman presented with a multicystic vulvar mass due to epidermal
      inclusion cysts, probably caused by trauma to the left labium minus at her last
      parturition.

PMID- 18825890
TI  - [Value of basic and intensive management of patients with heart failure; results
      of a randomised controlled clinical trial].
AB  - OBJECTIVE: To determine the efficacy of 2 nurse-directed programmes of different
      intensity for the counselling and follow-up of patients hospitalised for heart
      failure, compared with standard care by a cardiologist. DESIGN: Multicentre
      randomised clinical trial (www.trialregister.nl: NCT 98675639). METHOD: A total
      of 1023 patients were randomized after hospitalisation for heart failure to 1 of
      3 treatment strategies: standard care provided by a cardiologist, follow-up care
      from a cardiologist with basic counselling and support by a nurse specialising in
      heart failure, or follow-up care from a cardiologist with intensive counselling
      and support by a nurse specialising in heart failure. Primary end points were the
      time to rehospitalisation due to heart failure or death and the number of days
      lost to rehospitalisation or death during the 18-month study period. Data were
      analysed on an intent-to-treat basis. RESULTS: Mean patient age was 71 years, 38%
      were women, 50% had mild heart failure and 50% had severe heart failure. During
      the study, 411 patients (40%) were rehospitalised due to heart failure or died
      from any cause: 42% in the control group, and 41% and 38% in the basic and
      intensive support groups, respectively (differences not significant). The time to
      rehospitalisation or death was similar in the 3 groups: hazard ratios for the
      basic and intensive support groups versus the control group were 0.96 (95% CI:
      0.76-1.21; p = 0.73) and 0.93 (95% CI: 0.73-1.17; p = 0.53), respectively. The
      number of days lost to rehospitalisation or death was 39,960 in the control
      group; this number was 15% less in the intervention groups, but the difference
      was not significant. However, there was a trend toward lower mortality in the
      intervention groups. In all 3 groups, more visits occurred than planned, which
      may have had a considerable effect on care, notably in the control group.
      CONCLUSION: The results of this study indicated that the provision of additional
      counselling and support by a nurse specialising in heart failure as an adjuvant
      to intensive follow-up care provided by a cardiologist does not always lead to a
      reduction in rehospitalisation frequency.

PMID- 18825891
TI  - [Small risk of developing Lyme borreliosis following a tick bite on Ameland:
      research in a general practice].
AB  - OBJECTIVE: To investigate the percentage of ticks infected with Borrelia
      burgdorferi on the Dutch North Sea island of Ameland, and the risk of developing
      Lyme disease following tick bite on the island. DESIGN: Prospective,
      observational. METHOD: Ticks were collected from patients who visited a general
      practitioner and were tested for the DNA of B. burgdorferi. After 6 months the
      patients were interviewed by phone using a standardised questionnaire. RESULTS:
      From 2004-2006, 216 ticks were collected from 167 persons. Most ticks were
      removed within 24 hours. In 44 ticks (20.4%) B. burgdorferi DNA was detected.
      Follow up information was available on 146 persons, 41 (28.1%) of whom had been
      bitten by a Borrelia-positive tick. None of the persons developed a typical
      erythema migrans. From the 13 persons (9%) reporting a non-specific redness of
      the skin (diameter less than 5 cm) at the site of the tick bite, 5 had been
      bitten by a positive tick and 8 by a negative tick. One patient bitten by a
      positive tick reported systemic symptoms related to Lyme borreliosis, namely
      fatigue, perspiration and joint ache, without local redness. CONCLUSION: The
      probability of developing Lyme borreliosis was low even though a relatively large
      percentage of the ticks collected were positive for B. burgdorferi. This is
      probably connected to the fact that in the majority of cases the tick had been
      removed within 24 hours.

PMID- 18825892
TI  - [Pulmonary densities following a hysterectomy, caused by benign metastatic
      leiomyoma].
AB  - A 49-year-old woman, who had undergone a hysterectomy 17 years previously, was
      referred with thoracic pain located on the right side that had been present for
      several weeks. Thoracic imaging showed multiple pulmonary lesions on both sides.
      Histological investigation of a biopsy from one of these lesions revealed a
      benign metastatic leiomyoma. The patient was treated with gonadotropin-releasing
      hormone (GnRH) analogue. The lesions showed regression and the symptoms
      disappeared. Benign metastatic leiomyoma is a rare benign clinical entity in
      women of fertile age who have had a surgical intervention on the uterus because
      of uterus myomatosus. The therapeutic options are surgical resection, removal of
      the hormonal stimulus by administering progesterone or GnRH-analogues or
      bilateral ovariectomy.

PMID- 18825893
TI  - [An outbreak of measles at an emergency room].
AB  - A small outbreak of measles occurred after a 33-year-old female aircrew (cabin)
      member presented at an emergency room with fever. Three members of the hospital
      staff were infected: a 42-year-old man, a 33-year-old woman, and a 26-year-old
      woman. The first 2 patients had not been immunised, and the third had received 2
      immunisations according to the Dutch National Immunisation Programme. Vaccination
      of the 2 sero-negative patients within 48 h after exposure with the measles-mumps
      rubella vaccine (MMR) did not prevent the development of measles. Vaccination was
      deemed unnecessary in the third patient. No tertiary cases occurred. The same
      measles virus (genotype D5) was detected by PCR and sequencing in all 4 patients.
      Measles remains a risk for hospital staff members who have not acquired natural
      immunity. The current policy of immunising patients within 72 h after exposure to
      measles may not be sufficient. It also appears that immunisation through the
      Dutch National Immunisation Programme does not always protect against nosocomial
      infection. Providing MMR vaccination or boosters to hospital staff in certain
      departments might be beneficial.

PMID- 18825894
TI  - [Establishment of a national registry for sudden cardiac arrest in athletes].
AB  - Physical activity is healthy but can also trigger sudden cardiac arrest in
      vulnerable subjects. A Dutch national registry of sudden cardiac arrest in
      athletes has been established under the name of SPORTCOR. The aim of the registry
      is to obtain a better understanding of the incidence and causes of sudden cardiac
      arrest in athletes. Medical doctors and family members can register cases of
      sudden cardiac arrest in athletes at the website www.sportcor.nl. The website
      also provides background information for those who are interested.

PMID- 18825895
TI  - [Genetic cancer syndromes and reproductive choice: dialogue between parents and
      politicians on preimplantation genetic diagnosis].

PMID- 18825896
TI  - [Summary of the practice guideline 'Smoking cessation' from the Dutch College of
      General Practitioners].

PMID- 18825897
TI  - Management of a case of simultaneous abduction.

PMID- 18825898
TI  - What's your diagnosis? Bilateral ocular colobomas associated with trisomy 13
      syndrome.

PMID- 18825899
TI  - A thought on liability and reliability.

PMID- 18825900
TI  - Cataract surgery in pediatric uveitis.
AB  - Uveitis in children is associated with several sight-threatening ocular
      complications, including the formation of cataracts. The surgical management of
      uveitic cataracts in children is both challenging and controversial and, unlike
      in adult uveitic cataracts, surgery has historically been associated with poor
      visual outcomes. Juvenile idiopathic arthritis-associated uveitis in particular
      poses unique therapeutic challenges and the issue of correction of aphakia in
      these patients remains a contentious one. The growing use of immunotherapies and,
      where needed, targeted biologic agents in childhood uveitis increases our
      potential to implant lenses and predict outcomes. The authors review the
      available evidence base for the treatment of these children.

PMID- 18825901
TI  - Safety and efficacy of silicone rod frontalis suspension surgery for childhood
      ptosis repair.
AB  - PURPOSE: To evaluate the safety and efficacy of silicone rod frontalis suspension
      surgery for childhood ptosis. METHODS: The authors retrospectively studied 89
      consecutive children (110 eyelids) who had silicone rod frontalis suspension
      surgery for ptosis at Duke University Eye Center from 1983 to 2004. Marginal
      reflex distance1 (MRD1) elevation of 2 mm or more (vs preoperative MRD1) was
      considered satisfactory. MRD1 was measured as the vertical distance from the
      corneal light reflex in primary gaze to the upper eyelid margin. The
      postoperative eyelid symmetry (< or = 1 mm = satisfactory) was the difference
      between the MRD1 of the surgical and fellow eyelid. RESULTS: Median age at
      surgery was 45 months (range: 3 to 223 months) and median follow-up was 17 months
      (range: 1 to 88 months). Ptosis types (number of eyelids) were unilateral
      congenital (53), bilateral congenital (30), third nerve palsy (16), Marcus Gunn
      jaw wink (7), trauma (2), and myasthenia gravis (2). Median MRD1 elevation was 2
      mm or greater for all ptosis types, whereas satisfactory postoperative symmetry
      occurred in 60% of unilateral and 100% of bilateral congenital ptosis cases (last
      follow-up). Complications occurred in 10 eyelids (9%) and reoperation occurred in
      10 eyelids (9%). CONCLUSION: The use of silicone rod frontalis suspension surgery
      for ptosis repair in pediatric patients is modestly effective, with few
      complications and easy removal and adjustment.

PMID- 18825902
TI  - Screening for retinopathy of prematurity in a tertiary care newborn unit in
      Turkey: frequency, outcomes, and risk factor analysis.
AB  - PURPOSE: To report the frequency, risk factors, and outcomes of screening for
      retinopathy of prematurity (ROP). METHODS: Data of neonates with a gestational
      age of 34 weeks or less were analyzed and the predictors on the development of
      ROP were determined by using logistic regression analysis. RESULTS: Of the 318
      neonates, the frequency of ROP was 37.1% for any stage and 7.2% for stage 3 or
      greater. Treatment was needed in 16.1% of neonates with ROP. No treatment was
      required in neonates with a gestational age of greater than 32 weeks. Oxygen
      therapy, sepsis, gestational age of 32 weeks or less, and birth weight of less
      than 1,250 g were determined as the independent risk factors. CONCLUSIONS:
      Although frequency of ROP in Turkey is similar to that in the United States, the
      rate of severe ROP necessitating treatment seems to be higher in Turkey. Neonates
      with a gestational age of 32 weeks or less, a birth weight of less than 1,250 g,
      sepsis, and oxygen therapy may have a greater risk of developing ROP and
      screening should be intensified in the presence of these risk factors.

PMID- 18825903
TI  - Periorbital cellulitis in the era of Haemophilus influenzae type B vaccine:
      predisposing factors and etiologic agents in hospitalized children.
AB  - PURPOSE: The incidence of Haemophilus influenzae type B (HIB) infection, once the
      most common cause of periorbital cellulitis, declined dramatically after the
      introduction of HIB vaccine in 1990. The aim of the current study was to
      determine the predisposing factors and agents in the pathogenesis of periorbital
      cellulitis in hospitalized children in the post-HIB vaccination era. METHODS:
      Children with clinical findings of periorbital inflammation who were hospitalized
      in a tertiary pediatric hospital in Israel in 2000-2001 were observed
      prospectively. Special attention was directed to the predisposing medical
      condition in each case. RESULTS: One hundred sixty-three patients had a final
      discharge diagnosis of periorbital cellulitis. Mean age was 34 months (median =
      24 months). The predisposing conditions were conjunctivitis (42.9%), infected
      wound or trauma (20.9%), insect bites (9.8%), sinusitis (8%), dacryostenosis
      (4.9%), and Streptococcus pneumoniae bacteremia (0.6%). Children with
      conjunctivitis and sinusitis had the most severe inflammatory signs. None of the
      cultures was positive for HIB, although only 71% of the children had complete
      immunization. CONCLUSION: The epidemiology of periorbital cellulitis in children
      has changed in the post-HIB vaccine era. The most common predisposing medical
      conditions are conjunctivitis or an infected wound in the vicinity of the eye.
      Bacteremia is rarely a source of the disease. These findings have important
      clinical implications in terms of choice of treatment.

PMID- 18825904
TI  - Orbital rhabdomyosarcoma masquerading as a mucocele.
AB  - The authors describe a case of orbital rhabdomyosarcoma masquerading as a
      lacrimal mucocele in a newborn infant. Rhabdomyosarcoma is one of the few life
      threatening diseases that an ophthalmologist may be the first to diagnose. This
      case highlights the importance of close monitoring of such presentations in the
      newborn.

PMID- 18825905
TI  - Pupillography of relative afferent pupillary defects in amblyopia associated with
      peripapillary myelinated nerve fibers and myopia.
AB  - Pupillary responses to light were recorded in three patients with unilateral
      extensive myelinated nerve fibers and amblyopia by means of binocular infrared
      video pupillography. All of the patients had an afferent pupillary defect in the
      eye with myelinated nerve fibers. This finding supports the notion that this type
      of amblyopia is a severe form of anisometropic amblyopia that is often resistant
      to treatment.

PMID- 18825906
TI  - Ocular findings in a child with multiple endocrine neoplasia type 2b.
AB  - A 16-year-old girl was admitted with severe bilateral conjunctival hyperemia and
      stinging lasting for more than 1 year. Slit-lamp biomicroscopic examination
      revealed extremely thickened corneal nerves and multiple small plexiform
      subconjunctival neuromas. Both eyes had thickened upper and lower eyelids and a
      neuroma was found on the left upper conjunctival lid margin. On physical
      examination, a 2 x 3 cm nodule was detected within the thyroid gland. Medullary
      thyroid carcinoma was diagnosed by fine needle aspiration biopsy and
      thyroidectomy ensued. Further investigation with abdominal computed tomography
      revealed a pheochromocytoma (3 x 4.5 x 2 cm) of the right adrenal gland, which
      was removed surgically. Ophthalmologists must remember multiple endocrine
      neoplasia 2b in the presence of greatly thickened corneal nerves and
      subconjunctival neuroma because this may be the first sign of the disease. Early
      diagnosis and prophylactic thyroidectomy may be life saving.

PMID- 18825907
TI  - A rare association of familial exudative vitreoretinopathy and Turner's syndrome.
AB  - A 6-year-old girl presented with left divergent strabismus that had been noticed
      by her parents. She was known to have Turner's syndrome. On examination, she had
      tractional retinal detachment in the left eye and a temporal avascular area with
      neovascularization at the junction with the vascular area. Clinical features were
      characteristic of familial exudative vitreoretinopathy. This case is a rare and,
      to the authors' knowledge, the first reported association of familial exudative
      vitreoretinopathy and Turner's syndrome.

PMID- 18825908
TI  - Zipper injury to upper eyelid.

PMID- 18825909
TI  - Cell proliferation of the ileum intestinal mucosa of diabetic rats treated with
      ascorbic acid.
AB  - The objective of this work was to evaluate the effect of the ascorbic acid
      supplementation on the cellular proliferation on the ileum mucosa of diabetic
      rats. Fifteen 90-days rats were divided in the groups: control, diabetic and
      diabetic supplemented with ascorbic acid (DA). Two hours prior the sacrifice,
      they were injected with Vincristin. Semi-seriate histological cuts stained with
      HE were accomplished. About 2500 crypt cells from the intestinal mucosa were
      counted in order to obtain the metaphasic indexes. The height and depth of 30
      villi and 30 crypts were measured for each animal, respectively. The metaphasic
      indexes showed no significant changes when we compared the three groups: 20.2 +/-
      0.7 (control), 18 +/- 1.9 (diabetic) and 17 +/- 1.4 (DA) (p > 0.05). The values
      obtained from the crypts measurement were 221.2 +/- 8.5 (control), 225.3 +/- 9.5
      (diabetic) and 222 +/- 34 (DA). The villi of the control, diabetic and DA animals
      presented the following results: 301.7 +/- 25.33, 304.8 +/- 25.63 and 322.1 +/-
      45.77 respectively. The morphometric data were not different statistically (p >
      0.05). Summing up, the present work showed that there was no alteration in the
      cellular proliferation of the ileum of diabetic-induced rats supplemented with
      ascorbic acid.

PMID- 18825910
TI  - Rosette formation by macrophages with adhered T lymphocytes is precluded by
      inhibitors of antigen processing and presentation.
AB  - We had previously found in autologous human leukocyte cultures, in which dead
      neutrophils phagocytosis by macrophages occur, macrophages and T CD4 lymphocytes
      perform a selective cell-cell interaction showing many figures of either one, two
      or several T- lymphocytes adhering to a central macrophage were seen. Considering
      that antigen presentation would be necessary for the formation of these immune
      synapses, we attempted to block rosette formation (i.e., the formation of
      macrophage associations with at least three lymphocytes) by interfering with both
      antigen processing and presentation. Culture samples of autologous leukocytes
      from 7 healthy donors were subjected to either brefeldin A, chloroquine or to an
      anti-HLA DR antibody. Rosette formation was significantly inhibited in the
      treated samples (either with brefeldin A, chloroquine or the anti- HLA DR; ANOVA,
      p<0.001, as compared with the untreated controls). It is concluded that
      interference with antigen processing and presentation precludes the formation of
      these cell-cell interactions.

PMID- 18825911
TI  - Behavior of mesenchymal stem cells stained with 4', 6-diamidino-2-phenylindole
      dihydrochloride (DAPI) in osteogenic and non osteogenic cultures.
AB  - 4', 6-diamidino-2-phenylindole dihydrochloride (DAPI) is a DNA dye widely used to
      mark and trace stem cells in therapy. We here studied the effect of DAPI staining
      on the behavior of mesenchymal stem cells cultured in either a control, non
      osteogenic medium or in an osteogenic differentiation medium. In the control
      medium, the number of stem cells/field, as well as the number of fluorescent
      cells/field increased up to the sixth day in both control and DAPI-treated
      cultures. Afterwards, both the number of fluorescent cells and their fluorescence
      intensity decreased. Control cells were fusiform and with some long extensions
      that apparently linked them to neighboring cells, while DAPI-treated cells were
      mostly round cells with fine and short extensions. The trypan-blue exclusion
      method showed 99% cell viability in both groups, however, both alkaline
      phosphatase activity and the thiazolyl blue formazan assay (indicative of
      mitochondrial metabolism) gave significantly lower values in DAPI-marked cells.
      The mitochondrial mass, as indicated by specific staining and flow cytometry,
      showed no differences between groups. Mesenchymal stem cells gave origin to
      mineralized nodules in the osteogenic differentiation medium and there were not
      DAPI-marked cells on the ninth day of culture. Alkaline phosphatase activity,
      viability assay and number of cells/field and of mineralized nodules/field were
      similar in both groups. So, DAPI treatment did not change cell viability and
      proliferation during osteogenic differentiation of mesenchymal stem cells.
      However, since these cells loose DAPI marking after 9 days in osteogenic cultures
      suggests that DAPI may not be an effective marker for mesenchymal stem cells
      implanted in bone tissue for long periods.

PMID- 18825912
TI  - Morphologic and morphometric analysis of testis of Pseudis limellum (Cope, 1862)
      (Anura, Hylidae) during the reproductive cycle in the Pantanal, Brazil.
AB  - The spermatogenesis of Pseudis limellum, from the Southern Pantanal, Brazil, was
      studied from July 1995 to May 1996, through histological sections of the testis.
      The cells could be differentiated as: primary spermatogonia, large cells,
      generally with bilobed nucleus; secondary spermatogonia, smaller cells, with
      darker cytoplasm, chromatin of radial form; primary and secondary spermatocytes,
      differentiated according to the different stages of the nucleus during the
      successive cells divisions. Furthermore, we observed cells in process of
      morphologic differentiation: rounded spermatids much smaller, with nucleus
      containing chromatin in compacting process and cytoplasm reduction; elongated
      spermatids, generally parallel organized in well defined bundles, with the
      anterior region directed toward the periphery of the seminiferous tubule and the
      tail directed toward the lumen. Spermatozoa are free in the lumen of the
      seminiferous tubule. All the cells are organized as cysts, which are supported by
      a large amount of Sertoli cells. The spermatogenesis in P. limellum is very
      similar to that of other anurans, but peculiarities were observed regarding the
      organization of the germ cells, the great amount of free Sertoli cells in the
      lumen of testis collected in May, and the long cytoplasmatic extensions of the
      cells bearing pigments and involving the seminiferous tubule. The diameter of the
      seminiferous tubule (SD) exhibited an annual mean of 251.79 +/- 37.57 microm.
      Spermatozoa number by seminiferous tubule (SN) exhibited an annual mean of 306.66
      +/- 39.83, also with higher and lower values at each month. Variations in SD and
      SN were not significantly correlated with climatic variables. In this species,
      reproduction occurs throughout the year in ponds and flooded areas, despite the
      seasonal climate of the Pantanal. Although males varied in their annual
      reproductive activity, they were considered potentially reproductive in all
      months throughout the year.

PMID- 18825913
TI  - Genotoxic effect of Physalis angulata L. (Solanaceae) extract on human
      lymphocytes treated in vitro.
AB  - Physalis angulata L (Solanaceae) is a medicinal plant from North of Brazil, whose
      different extracts and infusions are commonly used in the popular medicine for
      the treatment of malaria, asthma, hepatitis, dermatitis and rheumatism. However,
      the genotoxic effects of P. angulata on human cells is not well known. The main
      purpose of the present study was to evaluate the in vitro genotoxic effects of
      aqueous extract of P. angulata using the comet assay and the micronucleus assay
      in human lymphocytes provided from 6 healthy donors. Treatments with P. angulata
      extracts were performed in vitro in order to access the extent of DNA damage. The
      comet assay has shown that treatments with P. angulata at 0.5, 1.0, 2.0, 3.0 and
      6.0 microg/mL in culture medium were genotoxic. Lymphocytes treated with P.
      angulata at the concentrations of 3.0 and 6.0 microg/mL in culture medium showed
      a statistically significant increase in the frequency of micronucleus (p<0.05),
      however, the cytokinesis blocked proliferation index (CBPI) was not decreased
      after P. angulata treatment. In conclusion, the present work demonstrated the
      genotoxic effects of P. angulata extract on human lymphocytes in vitro.

PMID- 18825914
TI  - Agmatine inhibits hypoxia-induced TNF-alpha release from cultured retinal
      ganglion cells.
AB  - The effect of hypoxia on the release of tumor necrosis factor-alpha (TNF-alpha)
      in transformed rat retinal ganglion cells (RGCs) and the effect of agmatine on
      the hypoxia-induced production of TNF-alpha in RGCs were evaluated. RGCs were
      cultured under hypoxic conditions with 5% oxygen, with or without 100 microM
      agmatine. The expression levels of TNF-alpha and its receptor-1 (TNF-R1) were
      investigated by Western blot analysis. After 6 hours of hypoxia, we noted an
      increase in TNF-alpha production in RGCs. Agmatine significantly reduced TNF
      alpha level after 12 hours of hypoxic treatment. The expression of TNF-R1 was not
      affected by the hypoxia or agmatine treatment. Our results show that agmatine
      inhibits the TNF-alpha production of RGCs in hypoxic condition. These results
      demonstrate a possible neuroprotective mechanism for agmatine against hypoxic
      damage in RGCs.

PMID- 18825915
TI  - Chromosome comparison between populations of the collared peccary, Tayassu
      tajacu, raised in captivity.
AB  - The collared peccary (Tayassu tajacu) is widely distributed over the American
      continent, being found from the south of the USA to the north of Argentina. In
      Brazil, it is spread all over the country, being one of the potential species to
      be raised in captivity. Therefore, the cytogenetic techniques could be a
      potential tool for reproductive monitoring of animals raised in captivity, mainly
      when destined for commercial purposes. This study had the objective of
      determining the chromosome number of two populations raised in captivity and
      characterizing them by GTG banding. For this purpose, an analysis was made of
      mitotic metaphases obtained from lymphocyte cultures made from blood samples of
      11 animals, six of which from the Northeast and five from the North of Brazil.
      The results of this analysis showed the same karyotype pattern for the species
      (2n=30 chromosomes and NF=48), besides corresponding to the South American
      pattern of the species, i.e., without a translocation between autosomes 1 and 8,
      chromosome X acrocentric, and no differences were found between the two
      populations studied. However, chromosomal polymorphisms were observed compared to
      data from the literature on populations from North and South America.

PMID- 18825916
TI  - [Characteristic features of the ranks genus and subgenus, and an intercalary rank
      "species complex" in ixodid ticks (Acari: Ixodidae)].
AB  - The work was carries our from the standpoint of the morphological conception of
      species. Vast collections of the Zoological Institute of the Russian Academy of
      Science testify to the existence of hiatuses in both genera and subgenera of
      Palearctic ixodids at all active phases of their ontogenesis. The fact that the
      subgenera of Palearctic genera have been well studies is notes, and composition
      of the subgenera is presented. The question of a taxonomic intercalary rank
      "species complex" is considered in detail in the context of the coevolution
      between some complexes of closely related species of ixodid ticks and some
      closely related species (genospecies, strains) of pathogens. The question of the
      taxonomic rank "species complex" in ixodid ticks as a phyletic species
      association is postulated on the basis of comparative ontogenetic data.
      Nomenclature status of the intercalary association "species complex" is specified
      in conformity with the fourth edition of the International Code of Zoological
      Nomenclature. Species composition of most studied complexes is presented. Some
      variants of morphological differentiation between species complexes within
      subgenus are considered. Significance of the taxonomic concept "species complex"
      for zoological. parasitological, and medical aspects of the ixodid ticks study
      was evaluated. Prognostic significance of the rank "species complex" for the
      study of the relationships between ixodid ticks and pathogens is discussed.

PMID- 18825917
TI  - [Variability of the life cycle duration in the taiga tick from mixed coniferous
      broad-leaved forests of the Udmurt Republic].
AB  - Seasonal cohorts of the unfed Ixodes persulcatus imago in the study area were
      found to consist of the ticks passed through three-, four-, and five-year life
      cycles, in the ratio 72.6, 26.4, and 2.0% respectively, on the base of mean long
      term values. Such ratio is established if 91.7% of larvae and 79.9% of nymphs
      develop without diapause, while the rest of larvae and nymphs develop with
      diapause. Mean duration of the tick generation is 3.3 years, with the
      fluctuations in certain of the years within the limits of 3.15-3.36 years.

PMID- 18825918
TI  - [Adaptation of sensory systems of gamasid mites (Parasitiformes, Gamasina) to
      dwelling in different environment].
AB  - The main complication sensory organs (the palpal organ and the tarsal sensory
      complex) of several species of gamasid mites were studied in scanning electron
      microscope. The species examined included permanent ectoparasites (Laelaps
      agilis, Laelaptidae), parasites of the nasal cavity and respiratory tract of
      birds (Sternostoma tracheocolum and Ptilonyssus reguli, Rhinonyssidae), dwellers
      of the sea littoral zone (Parasitus kempersi, Parasitus immanis, Parasitidae),
      and mites found on soil and on plants (Amblyseius barkeri, Parasitidae). Similar
      sensillar types, including olfactory SW-WP sensilla, contact chemo-mechanosensory
      (SW-UP and DW-UP) sensilla, termo-chemo-mechanosensitive (DW-WP) sensilla of two
      types, and tactile (NP) sensilla were found in all these species, excluding
      endoparasites, where some sensillar types (in particular, DW-WP sensilla with
      slit-like pores) are absent. It was shown that the topography of olfactory SW-WP
      sensilla of the tarsal complex reflects taxonomic position and phylogenetic
      history of mite genera, whereas the number of certain sensillar types and the
      degree of their development reflect ecological specialization of species. The
      palpal organ is characterized by rather uniform structure in mites of different
      families, dwellers of different environments, except for the endoparasites of the
      family Rhinonyssidae, where this organ is strongly reduced.

PMID- 18825919
TI  - [Component parasite communities in the minnow Phoxinus phoxinus (L.) from
      ecologically safe and polluted reservoirs].
AB  - A comparative analysis of the structure of component parasite communities in the
      minnow from ecologically safe or polluted to variable extent reservoirs was made.
      The analysis showed that the increase of the reservoir pollution by everyday
      drains, washings of fertilizers from the fields around and the dacha sections
      causes the change of dominant parasite species in the minnow, alteration of the
      sum of errors in the regression equation characterizing the spread of values of
      biomasses of the species forming the parasite community, and change of the
      "graphic" structure of the community. It is proved, that the high concentration
      of biogens has a destructive effect on natural systems, and at the same time
      causes the process of self-organizing, leading to the alteration of the community
      structure. As soon as even a small part of biogens is stopped to come into the
      reservoir, and the quality of environment is restored, the community restores its
      structure.

PMID- 18825920
TI  - [Trematodes of the genus Diplostomum Nordmann, 1832 from fishes of Lake Ladoga].
AB  - Metacercariae of the genus Diplostomum Nordmann, 1842 from fishes of Lake Ladoga
      were investigated. Sixteen trematode species of this genus were found. The
      species D. parviventosum Dubois, 1932, known previously only in Lithuania, was
      for the first time recorded in Lake Ladoga. The description and figure of its
      metacercaria are provided. Data on the infestation of different fish species by
      diplostomids are also given. Changes in the infestation of fishes by the
      Diplostomum metacercariae for a long-term period are analysed.

PMID- 18825921
TI  - [Anthropogenic impact on fish parasite fauna in lakes].
AB  - Anthropogenic influence on the fish parasite fauna in lakes is studied. Three
      types of the influence are considered, namely pollution by industrial effluent,
      anthropogenic eutrophication, and development of aquaculture. Their effects on
      the fish parasite fauna were found to be different.

PMID- 18825922
TI  - [Long-term changes in the parasite fauna of the bream Abramis brama L. in
      eutrophicated lake].
AB  - Data on the dynamics of parasite fauna if the bream Abramis brama for 50-year
      period are presented. The relation between trophic status of the reservoir,
      preferred type of the bream feeding, and the abundance of its parasites is shown.
      It was established, that the number of parasites developing in plankton organisms
      increases during the period of intensive eutrophication. Recent data on the
      parasite fauna of bream indicate preferred feeding of the host on benthic
      invertebrates, that is favourable to its growth. Permanent tendency to the
      increase of the bream invasion by the Diplostomum metacercaria could be a
      reliable parasitological indicator of the water body eutrophication.

PMID- 18825923
TI  - [Metazoan parasites of fishes from the Bug River].
AB  - Results if the ichthyoparasitological investigation of the Bug River carried out
      in 1996-1999 are reported. Twenty-nine metazoan parasite species from 7 classes
      were found in fishes from the studied area, with the total infestation rate
      63.9%. Thirteen of them parasitize fish at larval stages. Metacercariae of
      Opisthorchis felineus, which ate the agents of opisthorchosis in man and animals,
      were found in roach.

PMID- 18825924
TI  - [Parasite fauna of the snakehead Channa argus warpachowskii from Primorsky Krai].
AB  - Parasite fauna of the snakehead Channa argus warpachowskii was studied in water
      bodies of Primorsky Krai. Thirty-one parasite species were recorded in this host
      from the studied area according to original and literary data. Most part of these
      species are host-specific parasites of snakehead originated from Chinese-Indian
      region or parasites having a wide host range and able to infest almost all
      freshwater fishes. Moreover, three brackishwater species of parasites were found
      in the fishes introduced into the rivers of the southern part of Primorsky Krai.
      The causes of this invasion are discussed.

PMID- 18825925
TI  - [Monogenea of the fishes from Chu River basin].
AB  - Results of the long-term faunistic study of Monogenea from fishes of the Chu
      River basin are reported. Fauna of Monogenea in the studied area was found to
      include 51 species of 11 genera and 5 families. Thirteen parasite species
      occurred in the mountain part of the basin, and 40 species inhabit the valley
      zone, including 10 species of the Amur faunistic complex probably introduced to
      Kyrgyzstan together with acclimatized fishes.

PMID- 18825926
TI  - [Differences in activity of hippocampal and neocortical neurons in active and
      passive rabbits in negative emotional situations].
AB  - Activities of individual hippocampal (CA1 area) and neocortical parietal-temporal
      neurons were compared in active and passive rabbits in negative emotional
      situations during emotionally significant stimuli by plotting histograms of
      autocorrelations. As compared to passive animals, in active rabbits, the mean
      firing rate of hippocampal neurons was higher, bursting and periodic oscillations
      of discharges occurred more frequently. Oscillation periods in the theta 1 band
      (6.0-9.0 Hz) appeared more frequently (in the baseline state and active
      exploratory or defensive reactions), whereas those in the theta 2 band (4.0-5.9
      Nz), on the contrary, were infrequently observed (during freezing). The greatest
      changes in activity ofhippocampal neurons were observed during active locomotor
      responses of active rabbits. Intergroup differences in neocortical neuronal
      activities were less pronounced than in hippocampus. The results indicate that
      individual typological features in behaviour of animals appear in negative
      emotional situations and are reflected in activity of activity ofhippocampal
      (area CA1) and to lesser extent parietal-temporal neocortical neurons. The
      results suggest different activation levels of the septohippocampal system of
      active and passive rabbits and possible differences in the afferent input to the
      CA1 field.

PMID- 18825927
TI  - [Neurochemical mechanisms of food aversion conditioning consolidation in snail
      helix lucorum].
AB  - Effects of cycloheximide, protein synthesis inhibitor as well as serotonin
      receptor antagonist and NMDA receptor antagonist, on food aversion conditioning
      consolidation were studied in snail Helix lucorum. Food aversion conditioning was
      absent in snails after application of cycloheximide. Repeated training produced
      no food aversion conditioning for the same type of food in these snails without
      cycloheximide application. Food aversion conditioning was absent in snails after
      metiotepin, nonselective serotonin receptors antagonist, or after MK-801, NMDA
      glutamate receptors antagonist, applications. At the same time, repeated training
      produced facilitated food aversion conditioning for the same type of food in
      these snails. Our experiments were the first which showed that effect on
      different molecular mechanisms evoked reversible or irreversible disruption of
      long-term memory consolidation during the same learning. It was suggested that
      suppression of retrieval produced reversible effect whereas disruption of memory
      storage initiated irreversible effect on long-term memory consolidation.

PMID- 18825928
TI  - [The influence of intracysternal insulin administration on the rat temporal
      behaviour dynamics].
AB  - Rat behaviour in the open field and elevated plus-maze was analyzed in rats after
      intracysternal administration of 2.5, 25, 50 and 200 ng of insulin in 45 min, 24
      hrs and on the 9th day after single injection. Dose-dependent changes in 45 min
      occurred in both behavioural tests: insulin in low doses (2.5 and 25 ng)
      increased probability of locomotion and investigative activity in open field,
      while insulin in high doses (50 and 200 ng) did not alter locomotor activity and
      showed tendency to weakening of the investigative behavior (especially in the
      dose of 50 ng). Tendency was found in 24 hrs to increase probability of
      investigative behavior in open field after injection of 25 ng of insulin,
      although on the 9th day after insulin administration this behaviour increased in
      all experimental groups for all used doses. Insulin in the doses 2.5 and 200 ng
      decreased anxiety in elevated plus-maze in 45 min during the first five min; the
      doses 2.5 and 25 ng at the second five min exerted the same effect. In 24 hrs,
      the anxiety level increased for the doses 50 and 200 ng, and there was a tendency
      for an increase in the doses 2.5 and 25 ng; anxiety was decreased on the 9th day
      for all used doses of insulin. Thus, single insulin administration induced
      weakness of non-associative memory in open field on the day 2 and day 9 as well
      as increase of anxiety level on the day 2 and decrease of anxiety level on the
      day 9 in elevated plus-maze.

PMID- 18825929
TI  - [Hemodynamic mechanisms of the pulmonary artery pressure and blood flow changes
      following vasoactive pressor drugs injection].
AB  - The character and values of changes of the pulmonary and systemic hemodynamics
      following epinephrine, norepinephrine and angiotensin intravenous injection were
      studied in acute experiments on the anesthetized cats. After catecholamines
      injection pulmonary blood flow was always increased, meanwhile pulmonary artery
      pressure can be elevated (in the most observations) or decreased. In the cases of
      angiotensin administration the pulmonary blood flow could be augmented or
      decreased; pulmonary artery pressure had been increased or decreased
      independently from the character of changes of pulmonary flow. Thus, linear
      correlation between shifts of the pulmonary artery pressure and pulmonary blood
      flow had not been revealed. The changes of the pulmonary artery pressure were not
      correlated with the pulmonary vascular resistance ones; however they had strong
      relationship with the changes of the left atrial pressure. If the left atrial
      pressure was decreased the pulmonary artery pressure elevation was less,
      comparing with its values in experiments, where the left atrial pressure was
      increased; in the case of depressor shifts of pulmonary artery pressure, the left
      atrial pressure was also decreased. The character and values of the pulmonary
      blood flow changes were strongly correlated with the changes of the venous
      return; however they had no linear correlations with the right and left atrial
      pressures and pulmonary vascular resistance changes. Thus we concluded, that
      hemodynanics mechanisms of the pulmonary artery pressure and flow changes
      following vasoactive pressor drugs injection changes are different.

PMID- 18825930
TI  - [Basic laws of blood screw motion in human common carotid arteries].
AB  - The basic laws of blood screw motion in common carotid arteries in people were
      determined by means of modern ultrasound techniques for the first time. 92
      healthy adults, aged 18-30, were examined. The blood flow in the middle one-third
      of common carotid arteries was registered by means of Color Doppler Imaging and
      impulse Doppler with the help of ultrasound Medison 8000EX scanner by linear
      transducer of 5-9 MHz. The steady registration of blood screw motion in both
      common carotid arteries in Color Doppler Imaging regimen was observed in 54.3 %
      of cases. The direction of screw stream rotation in most cases (54%) was multi
      directed: in the right common carotid artery it was right, in the left common
      carotid artery--left (48%), and in 6% of cases it was reverse. For 46% of cases
      blood rotation in both common carotid arteries was one-directed (26%--right, 20%-
      left). The velocity parameters of rotation component of blood motion were
      determined, maximum velocity being 19.68 +/- 5.84 cm/sec, minimum--4.57 +/- 2.89
      cm/sec, average--7.48 +/- 2.49 cm/sec, angular--10.7 +/- 2.49 sec(-1). The rated
      velocity of blood cells motion in screw motion with regard of screw current lines
      to the vessel vertical axis makes up from 158.67 +/- 32.79 to 224.39 +/- 46.37
      cm/sec.

PMID- 18825931
TI  - [Ratio of haematology indexes in exudation of "skin window" and venous blood].
AB  - The data obtained revealed the maintenance of basophiles; monocytes and large
      granular lymphocytes were higher in the skin then in the venous blood. The level
      of eosinophiles and lymphocytes were lower in the skin. Concentrations of the
      polymorphic leucocytes were equal in the skin and in the blood.

PMID- 18825932
TI  - [The influence of calcineurin gene polymorphism on morphofunctional
      characteristics of cardiovascular system of athletes].
AB  - The aim of the study was to investigate allelic distribution of calcineurin gene
      (CNB; 5I/5D polymorphism) in athletes of cyclic sports (n = 673) and controls (n
      = 1073), and to find interrelation between genotypes and risk of left ventricular
      hypertrophy and physical performance of athletes. Genotyping was performed by
      restriction fragment length polymorphism. Echocardiography was performed by
      ultrasound scanner Aloka-3500. Physiological parameters were evaluated by
      spiroergometry using MetaMax 3B Gas Analyzer. The frequency of CNB D allele was
      significantly lo- wer in athletes than in controls (5.5 vs. 8.8 %; p = 0.0005),
      and decreased with the growth of skills. We found that CNB D allele was
      associated with increased left ventricular mass index and low values of physical
      performance (when maximal power production capacity and maximal oxygen
      consumption were measured). Thus, CNB gene 5I/5D polymorphism is associated with
      the risk of left ventricular hypertrophy and physical performance of athletes.

PMID- 18825933
TI  - [Interrelationships among cardiohaemodynamic parameters in human postnatal
      ontogenesis].
AB  - In one-day old humans and to 20 years of age, the stroke volume (SV) increases
      from 5.4 +/- 0.4 to 70 +/- 5 ml, the arterial systolic pressure (ASP)--from 60 +/
      5 to 120 +/- 10 mm Hg. Heart rate decreases to 70 +/- 4/min from 136 +/- 10/min
      at birth. The N coefficient as the SV/ASP ratio parameter grows from 0.1 in
      children to 0.6 by 20 years of age. The peripheral resistance in the arterial
      system scope from the left ventricle exit tract to the middle of the humeral
      artery amounts up to 76 mm Hg x ml(-1) x min(-1) in newborn infants and in adults
      it is reduced to 28. Reduction of post-load decreases 6-fold the total amount of
      the heart mechanical work of pumping the SV into the vascular system.

PMID- 18825934
TI  - [The effect of amplitude-frequency characteristics of the noise-covered test
      stimulus on the form of visual evoked potentials].
AB  - Visual evoked potentials in response to reverse checkerboard patterns presented
      in additive noise were analyzed. An induced by noise changes in visual evoked
      potentials form and in amplitude-frequency spectrum of checkerboard patterns were
      compared. It was found that character of visual evoked potentials form alteration
      correlated with stimulus amplitude-frequency spectrum alterations. Results
      obtained here support Gestalt-psychology view about using by visual system a
      spatial-frequency but not a discrete information description.

PMID- 18825935
TI  - [Dehydroepiandrosterone sulfate effect at the conversion of corticosterone to 11
      dehydrocorticosterone in stress conditions: the scheme of regulation].
AB  - It had been shown that the reaction of conversion of corticosterone (CS) to 11
      dehydrocorticosterone (11-DHCS) was increased in chronic intermissions, but not
      in sharp stress influences in male rats, especially under dehydroepiandrosterone
      sulfate (DHEAS) employment. The injection of naltrexone 20 min before DHEAS in
      dose 0.1 mg/kg which selectively blocked the mu-opiate receptors canceled this
      effect that indicated the participation of in-opiate receptors in such
      regulation. The DHEAS effect realized through the endogenous ACTH, and such was
      of the central nature. On the base of ourselves and the literature dates we
      intraduced the scheme of DHEAS- and mu-opiate-dependent regulation of CS/11-DHCS
      interchangings.

PMID- 18825936
TI  - [Effects of the corticoliberin on synaptic transmission in the rat olfactory
      cortex slices in water-immersion model depression].
AB  - Corticoliberin (corticotrophin-releasing hormone, CRH) regulated of endocrine,
      autonomic and immune response to stress and is a mediator of anxiety in
      behavioral response. We studied the effect of corticoliberin on neuronal activity
      after microstimulation of olfactory cortex slices. Wistar rats strain were
      selected in T-maze labyrinth according to active and passive strategy of the
      adaptive behavior. The rats were exposed to water-immersions stress and after 10
      days from their brain the olfactory cortex slices were prepared. The evoked focal
      potential were registered after perfusion with 0.1 mcM of CRH. It was revealed
      that in 60% of the slices of the active rats CRH induced the small decrease of
      excitatory amplitude but the increase amplitude inhibitory postsynaptic
      potential. In 40%, CRH induced the depression of synaptic transmission. Addition
      of CRH in incubation medium of the passive rat slices related, blockade the
      synaptic transmission.

PMID- 18825937
TI  - [Condition of oxidation homeostasis and possibility of its correction in
      experimental rheumatoid arthritis].
AB  - The data on condition of oxidation homeostasis in experimental rheumatoid joint
      inflammation in rabbits are presented. Against a background of expressed local
      and general activity of the inflammatory process in the synovial medium of the
      affected joint, the peroxide-antioxidative imbalance (increase of level ofmalonic
      dialdehyde and the activity of ceruloplasmin) and also lowering of pH and pO2,
      rise of lactate blood level are detected. The intraarticular introduction of the
      antioxidant ceruloplasmin promoted the normalization of synovial medium of
      affected joints.

PMID- 18825938
TI  - [Behavior and spatial learning in birds in radial maze].
AB  - Studies of spatial learning and memory of birds in radial maze are reviewed. The
      radial maze variants (standard, giant and open-field analog) are described;
      procedural problems of bird testing are discussed. Radial maze task performance
      of birds is compared with that of laboratory rats as a well-studied standard.
      Specific features of spatial learning in various taxonomic avian groups (pigeon,
      tits, corvids, chickens and others) are considered. The results of spatial memory
      studies in closely-related species with different ecology (food storing behavior,
      degree of caching specialization) and experiments with migrant birds and homing
      pigeons are discussed.

PMID- 18825939
TI  - [Individual behavior depending on reinforcement prediction errors and
      environmental uncertainty].
AB  - Different types of individual behavior are described in terms of under- or
      overestimation of reinforcement characteristics by the brain under conditions of
      uncertainty of reinforcement presentation. The following important biological
      characteristics of a subject are discussed, such as anxiety, fear, neuroticism,
      impulsiveness, self-control and psychoticism that determine the main individual
      typological features in human and animals. Some modern biological theories of
      "individuality" and recent animal studies of neuronal activity of the frontal
      cortex and striatum depending on validity and delay of reinforcement are
      analyzed.

PMID- 18825940
TI  - [Individual propensity to active or passive behavior during exposure to emotional
      stress in individuals with various blood cortisol levels].
AB  - Effects of baseline and reactive blood cortisol on operator's performance were
      studied in subjects with active of passive behavioral reactions under exposure to
      stress. The type of behavioral reaction to stress (shift in the rates of
      omissions or false alarms) was found to be associated with the baseline blood
      cortisol and its levels averaged in the course of the experiment. Subjects with
      active reaction (stress produces an increase in the rate of errors of the false
      alarm type) were characterized by the low cortisol level, whereas its high level
      was observed in subjects with passive reaction (stress produces an increase in
      the rate of errors of the omission type). Individuals with high baseline cortisol
      level and those with the passive reaction to stress exhibited enhanced
      cardiovascular reactivity during performance in normal conditions and its
      reduction during the performance under exposure to stress.

PMID- 18825941
TI  - [EEG correlates for efficiency of the nonverbal creative performance (drawing)].
AB  - This work was aimed at a search for EEG corellates of efficiency of nonverbal
      creative performance. Standardized Torrens technique which makes it possible to
      quantitatively assess creativity was used. The EEG records were performed before
      and during test performance, EEG parameters were compared to Torrens scores on
      three scales: flexibility, originality and efficiency. Absolute values of spatial
      synchronization, coherence and spectral power both in the baseline and during the
      performance were calculated. Changes in these parameters were traced during the
      transition from the state of quiet wakefulness to creative performance. The
      narrow-band analysis of coherence and spectral power allowed the number and
      orientation of processes associated with creativity scales to be assessed. The
      absence of substantial EEG changes during the test performance is indicative of
      the steady, nondynamical functional state of the brain.

PMID- 18825942
TI  - [Echo thresholds of the precedence effect in the vertical plane].
AB  - Echo thresholds were measured for two configurations of loudspeakers in the
      vertical plane. The first configuration was characterized by the lead sound
      presentation from a loudspeaker placed in front of a subject, whereas the lag
      sound was presented from the loudspeaker above the subject's head. In the second
      configuration, the lead and lag sounds were presented from the same loudspeakers
      but in reverse order. All the stimuli were broadband noise bursts in the
      frequency range of 5-20 kHz. Burst durations were 5, 10, 20, and 100 ms. Average
      echo thresholds differences were significant only for the signals of 100 ms in
      duration (F (1, 16) = 6.28; p < 0.05). For the other signals (5, 10, 20 ms),
      there was no significant effect of location of lead and lag signals (p > 0.05).

PMID- 18825943
TI  - [Cooperative neuronal activity of the n. accumbens and the frontal cortex in cats
      trained to choose stimuli of various value].
AB  - It was shown that the two-way interaction between neurons of the frontal cortex
      and n. accumbens progressively increases, whereas their regularity simultaneously
      decreases with the rise in impulsiveness and drop in self-control in behavior. In
      case of the long-latency instrumental reactions, a control of the frontal cortex
      neurons by neurons of the n. accumbens weakens during presentation of conditioned
      stimuli only in "impulsive" animals, which is correlated with low network
      activity of the n. accumbens. Comparison of patterns of fronto-accumbal
      interactions during performance of the same type of activity revealed similar
      correlations in the neuronal pairs before and during presentation of conditioned
      stimuli, whereas different patterns corresponded to different types of activity.

PMID- 18825944
TI  - [Formation of the spatial memory in rats with ischemic injury in prefrontal areas
      of the cortex--effects of a sinthetic analogue of ACTH(4-7)].
AB  - It was shown, that photochemically induced thrombosis of blood vessels in
      prefrontal areas of the cortex lead to the formation of well-defined infarct
      zone. Bilateral prefrontal cortex injury impair acquisition of the Morris water
      maze on postoperative days 20-24. Chronic treatment of brain-injuried rats with
      peptide semax, a synthetic analogue of ACTH(4-7), at a dose of 250 microg/kg
      (intranasal, once a day) during six days after photothrombosis resulted in
      restoration of spatial learning ability. The observed long-lasting antiamnesic
      effects of the semax are probably caused by its strong neuroprotective action,
      and ability to induce synthesis of nerotrophic factors.

PMID- 18825945
TI  - [Comparative analysis of neuronal impulse activity in the CA1 and CA3 hippocampal
      fields in various typological groups of rats under exposure to emotional
      stimuli].
AB  - Hippocampal unit activity in the right and left CA1 and CA3 fields was studied in
      rats divided in two groups by the method of "emotional resonance": the animals
      which did ("A") and did not stop ("E") crying of a partner rat. The rate of
      neuronal firing was studied in the state of hunger, satiation, and under exposure
      to intracranial electrical stimulation of the emotional positive and negative
      structures of the brain. It was shown that units increasing their activity after
      satiation prevailed in the CA1 field, whereas, in the CA3 field, the majority of
      neurons decreased the firing rate under these conditions. Intracranial
      stimulation, especially positive, increased the rate of firing in both
      hippocampal fields. Under exposure to emotional stimuli, "A" rats displayed
      asymmetric unit activity only in the CA1 field, whereas in "E" rats, activity was
      asymmetric only in the CA3 field. Under these conditions in both groups of
      animals, the left-side activity was more intense than the right-side activity
      independently of the emotion sign.

PMID- 18825946
TI  - [Depression-like and anxiety-related behaviour of rats fed with magnesium
      deficient diet].
AB  - The aims of this study were to estimate of psychomotor activity, emotional status
      and magnesium (Mg) content in blood of rats fed with Mg-deficient diet for 49
      days; and to find out whether the combination of vitamin B6 with Mg will reveal
      antidepressant- and anxiolytic-like activity and reduce the length of the
      treatment needed to recover rats from Mg-deficient condition. To induce
      hypomagnesemia, seventy-nine rats were placed on a Mg-deficient diet (Mg content
      < or = 15 mg/kg) and demineralized water for 7 weeks. Eight control rats were fed
      a basal control diet. On the forty-ninth day of Mg-deficient diet, rats were
      treated one of the six supplementations: Mg L-aspartate alone and in combination
      with pyridoxine, MgCl2 x 6H2O alone and in combination with pyridoxine, Magne B6
      (Mg lactate with pyridoxine) and Mg sulfate (50 mg Mg and 5 mg vitamin B6 per
      kg). In our study Mg-deficiency was associated with depleted intraerythrocytic
      (0.748 +/- 0.036 vs. 1.83 +/- 0.026 mmol/l, p < 0.001) and plasma (0.567 +/-
      0.029 vs. 1.20 +/- 0.030 mmol/l, p < 0.001) Mg level compared to control rats. It
      was shown Mg deficiency resulted in depression-like and anxiety-related behavior
      in rats. Open field test result in rats including locomotor activity (number of
      crossed squares) and vertical activity (number of standing on hind paws), number
      of visiting in central squares were decreased significantly. In the elevated plus
      maze test, the number of visiting open arms (by 63.6%) and residence time (by
      78.5%) of rats were significantly less as compared with the control group. In the
      forced swimming test, time immobile was significantly increased (by 70.2%) and
      time of swimming was decreased (by 15%) compared to control. Mg salts alone and
      in combination with vitamin B6 administered to Mg-deficient rats increased the Mg
      level in plasma and erythrocytes. Furthermore, this increase was in relation to
      vitamin B6 given to the animal. It was established, that the application of Mg L
      aspartate and MgCl2 x 6H2O in combinations with pyridoxine led to correction of
      behavioural disturbances of Mg-deficient animals. Antidepressant- and anxiolytic
      like activity of studied salts was comparable with those observed in Magne B6
      treatment and significantly higher than in Mg sulfate treatment.

PMID- 18825947
TI  - [The anxyolytic effect of mild hypobaric hypoxia in a model of post-traumatic
      stress disorder in rats].
AB  - The impact of mild hypobaric hypoxia on the development of anxiety-like state in
      rats in experimentally simulated human post-traumatic stress disorder was
      studied. Three-trial exposure to mild hypobaric hypoxia (360 mm Hg for 2 hours
      daily, for 3 days) in preconditioning or post-conditioning mode performed,
      respectively, before or after exposure to severe traumatic stress in the "stress
      restress" model produced a significant anxiolytic effect on the rat open-field
      and plus-maze behavior. Anxiolytic effect of modem antidepressant Paxil (20 mg/kg
      daily, for 3 days) was weaker. This drug produced side-effects on particular
      behavioral characteristics in the open field. The conclusion was made on the
      efficacy of mild hypobaric hypoxia and the possibility of its implementation as a
      medication-free tool for prophylaxis and correction of post-traumatic stress
      disorder.

PMID- 18825948
TI  - [Chronic effect of thyroxine on behavior and brain serotonin receptors in mice
      with the sharp difference in predisposition to catalepsy].
AB  - Effects of chronic thyroxine treatment (2mg/l, 60 days) on catalepsy, functional
      activity and expression of 5-HT(1A) and 5-HT(2A) receptors genes in the brain
      were studied in adult males of catalepsy-prone ASC and catalepsy-resistant AKR
      mouse strains. Thyroxine caused an appearance of cataleptics in AKR, but produced
      an anticataleptic effect on ASC mice. Chronic thyroxine treatment increased the
      functional activity and expression of 5-HT(2A) receptors in the frontal cortex in
      AKR, but not in ASC mice. Hormone markedly attenuated hypothermic effect of 8-OH
      DPAT, 5-HT(1A) receptor agonist, but did not affect the expression of 5-HT(1A)
      receptors in ASC mice. The results suggest the involvement of the 5-HT(2A)
      receptors in the cataleptogenic and the 5-HT(1A) receptors in the anticataleptic
      effects of hormone.

PMID- 18825949
TI  - [Correlation of the rat behavior after immobilization with structural
      reorganization in the motor cortex].
AB  - Behavioral changes and accompanying morphological neuron-glia reorganization in
      the rat brain were compared after emotional stress. Wistar rats (n = 20) were
      stressed by the interrupted immobilization, which was carried out during one week
      7-8 h daily. Behavioral immobilization of rats was accompanied by an increase in
      horizontal and vertical locomotors activity and in duration of the III and IV
      phases of grooming ("comfortable" grooming) in the "open field" test. The
      morphometric studies showed a statistically significant increase in the density
      of hypoxic neurons in the right neocortex of the experimental animals as compared
      with control. Hypoxic changes in neurons were of functional character.
      Experimental rats can be considered as a model of redistribution of functional
      brain activity with preferential intensification of the left brain hemisphere.

PMID- 18825950
TI  - [Chitinases in bioengeneering research].
AB  - Techniques of introduction of foreign genes into the plant genome have been
      intensely developed in order to directionally improve properties of crops. One of
      the key directions in plant bioengineering is searching for and analyzing
      promising genes, in particular, to construct genotypes with high resistance to
      pathogens and pests. In this review, the use for this purpose of transgenes
      coding for chitinase family enzymes is considered. Many of these transgenes have
      proved to be efficient factors for elevating plant resistance to pathogenic
      fungi.

PMID- 18825951
TI  - [Expression of anti-tumor recombinant IgG- and IgE-like genes in eukaryotic
      cells].
AB  - The tandem of humanized variable VL and VH genes (ScFv fragment 4D5) possessing a
      high affinity to the HER-2/neu oncogene (the epidermal growth factor receptor
      expressed in many types of human tumors) was attached through a flexible linker
      to the second exon of human antibodies of IgG1 or IgE isotypes constant gene. The
      humanized construct of IgE isotype was generated for the first time. Genes of the
      recombinant antibodies were cloned into the pCl-neo vector under the control of
      universal cytomegalovirus (CMV) promoter. Transfected HEK-293 cells efficiently
      produced antibodies of the corresponding isotypes IgE and IgG1. The results of
      Western blotting confirmed homogeneity of the expressed antibodies, which had the
      predicted molecular weight and specifically interacted with the HER-2/neu. The
      attachment of leader peptide to the 5'-end of the gene resulted in the
      preferential accumulation of recombinant antibodies in the cultural medium. These
      results indicate that de novo constructed humanized immunoglobulin genes express
      functionally active, single-chain recombinant antibodies in eukaryotic cells.

PMID- 18825952
TI  - [Molecular evolution of poxviruses].
AB  - Previous restriction fragment length polymorphism analysis divided variola virus
      (VARV) strains into two subtypes, one of which included West African and South
      American isolates. This allowed a dating to be introduced for the first time in
      estimation of the VARV evolution rate. The results were used to analyze the
      molecular evolution of the total family Poxviridae. Comparisons of the known
      nucleotide sequences were performed for the extended conserved central genome
      region in 42 orthopoxvirus strains and for the eight genes of multisubunit RNA
      polymerase in 65 viruses belonging to various genera of the family Poxviridae.
      Using the Bayesian dating method, the mutation accumulation rate of poxviruses
      was estimated at (1.7-8.8) x 10(-6) nucleotide substitutions per site per year.
      Computations showed that the modem poxvirus genera started diverging from an
      ancestral virus more than 200 thousand years ago and that an ancestor of the
      genus Orthopoxvirus emerged 131 +/- 45 thousand years ago. The other genera of
      mammalian poxviruses with a low GC content diverged approximately 110-90 thousand
      years ago. The independent evolution of VARV started 3.4 +/- 0.8 thousand years
      ago. It was shown with the example of VARV and the monkeypox virus (MPXV) that
      divergent evolution of these orthopoxviruses started and the West African
      subtypes of VARV and MPXV were formed as geographical conditions changed to allow
      isolation of West African animals from other African regions.

PMID- 18825953
TI  - [Interaction between checkpoint genes RAD9, RAD17, RAD24, and RAD53 involved in
      the determination of yeast Saccharomyces cerevisiae sensitivity to ionizing
      radiation].
AB  - Mechanisms for genetic control of cell division cycle (checkpoint control) have
      been studied in most detail in yeast Saccharomyces cerevisiae. To clarify the
      role of checkpoint genes RAD9, RAD17, RAD24, and RAD53 in cell radioresistance,
      double mutants were analyzed for cell sensitivity to ionizing radiation. Double
      mutants carrying mutations in combination with mutation rad9Delta were shown to
      manifest the epistatic type of interaction. Our results suggest that checkpoint
      genes RAD9, RAD17, RAD24, and RAD53 belong to a single epistatic group designated
      RAD9 and govern the same pathway. Genes RAD9 and RAD53 have a positive effect on
      sensitivity to gamma-radiation, whereas RAD17 and RAD24 have a negative effect.
      Interactions between mutations may differ when considering their sensitivity to
      gamma-radiation and UV light; mutations rad9Delta and rad24Delta were shown to
      manifest the additive effect in the first case and epistatic effect in the
      second.

PMID- 18825954
TI  - [Specifics of anaphase chromatid disjunction in Drosophila melanogaster mitotic
      mutants].
AB  - Anaphase chromatid behavior defects (CBDs) were quantitatively and qualitatively
      studied in nerve ganglion cells of third-instar larvae of several control wild
      type Drosophila melanogaster strains and four strains with mutations of the
      aar(v158), ff3, mast(v40), and CycB(2g) cell-cycle genes. A linear specificity
      was observed for the CBD frequency, type, determination, and correction
      probability. The probability of anaphase CBD correction was close to unity in the
      control strains and lower in the mutant strains. The lower correction probability
      in the mutant strains was explained in the context of two findings, that the
      mutations induced the CBDs that were atypical of the wild-type strains and were
      potentially uncorrectable in anaphase and that the mutations negatively affected
      the relative anaphase time in mitosis.

PMID- 18825955
TI  - [The effects of inbreeding and low temperature on the pattern of chromosome
      synapsis in the ovarian nurse nuclei of Drosophila melanogaster strains].
AB  - The effects of inbreeding and low temperature on the pattern of homologous
      chromosome synapsis in ovarian nurse cell nuclei of Drosophila melanogaster
      strains were studied. Exposure to decreased temperature (16 degrees C) caused a
      noticeable increase in the rate of asynapses of homologous chromosomes, whereas
      this effect was insignificant for F30 inbreeding generation. Long-term inbreeding
      has a substantial effect on the relative positions of chromosomes in the nurse
      cell nuclei. This is visually evident only in the interstrain hybrids between
      highly inbred strains LA (F923) and HA (F923) or between either strain and
      laboratory strain Canton S or the flies from the natural population, where
      abnormalities in homologous chromosome synapsis are observed in virtually all
      nuclei.

PMID- 18825956
TI  - [Investigation of systemic control of plant cell division and differentiation in
      the model of tumor growth in radish].
AB  - The study addresses the control of plant cell division and differentiation using
      the model of tumor-forming lines of radish. Expression of the genes involved in
      control of the cell cycle (CycD3), maintenance of meristematic cell activity
      (STM, WUS, and KNAT1), and primary response to cytokinin (ARR) was studied in
      inbred radish lines characterized by tumor growth at different stages of
      development. The influence of exogenic cytokinin on the expression of the genes
      of interest is analyzed. The possible role of the CycD3, KNAT1, STM, WUS, and
      ARR5 in tumor formation in radish is discussed.

PMID- 18825957
TI  - [Molecular genetic analysis of wild soybean (Glycine soja Sieb. & Zucc.)
      population structure in anthropogenic and natural landscapes of Primorskii krai].
AB  - The data are presented on genetic population structure of wild soybean growing in
      natural and anthropogenically disturbed landscapes of Primorskii krai of the
      Russian Federation. Comparative analysis showed that wild soybean populations
      exposed to anthropogenic influence exhibited lower genetic diversity than natural
      populations. Recommendations on conservation of the wild plant gene pools using
      comparative data on population genetic structures are made.

PMID- 18825958
TI  - [Phylogeography of the Siberian newt (Salamandrella keyserlingii) by
      mitochondrial DNA sequence analysis].
AB  - Differentiation of geographical populations of the Siberian newt Salamandrella
      keyserlingii throughout the species range was analyzed using a fragment of the
      cytochrome b gene. The population of the Primorye region (Russian Far East) is
      separated to the greatest extent; the Japanese and South Kuril populations are
      the next most separate. These populations are possibly subspecies. Geographical
      differentiation of populations in the Siberian part of the species range is
      lower, lacks a clinal variation, and is irregular. The molecular variation of S.
      keyserlingii supports the hypothesis that several primary vicarious refugia of
      pre-Pleistocene differentiation of a common ancestor of Salamandrella occurred in
      the southeastern part of its current distribution range and that northern and
      western regions were gradually colonized via repeated steps of expansion and
      retreat in the Siberian part of the modem species range.

PMID- 18825959
TI  - [Instability of B-chromosomes in somatic and germline cells of Apodemus
      peninsulae].
AB  - Instability of B-chromosomes was estimated in somatic and germline cells of
      samples Apodemus peninsulae from different localities of the species range. In 84
      out of 188 animals (45%), in cells assessed for B-chromosome mosaicism, bone
      marrow cells with different B-chromosome number were observed. The numbers of B
      chromosomes in spermatocytes at the pachytene stage were estimated in ten males.
      It was shown that the average number of B-chromosomes and the number of cell
      clones in germline cells was higher than the corresponding numbers in bone marrow
      cells. The higher number of B-chromosomes and their higher variability in
      germline cells than in somatic cells suggest the existence of a mechanism of
      premeiotic accumulation of B-chromosomes in spermatogenesis of A. peninsulae.

PMID- 18825960
TI  - [Molecular genetic relationships among east Palearctic ground squirrels of the
      genus Spermophilus (Sciuridae, Rodentia)].
AB  - Genetic diversity in the four east Palearctic ground squirrel species of the
      genus Spermophilus--S. undulatus, S. parryi (subgenus Urocitellus), S. dauricus,
      and S. relictus (subgenus Citellus)--- was investigated using RAPD PCR with ten
      random primers. Siberian chipmunk, Tamias sibiricus, was used as an outgroup.
      Molecular markers for different taxonomic ranks were identified, including those
      for the genera Spermophilus and Tamias, subgenera Urocitellus and Citellus, as
      well as for each of the four species, S. undulatus, S. parryi, S. dauricus, and
      S. relictus. For the ground squirrel species and subgenera, genetic
      differentiation indices (H(t), H(s), D(st), G(st), Nm, and D) were calculated. In
      addition, for these groups the NJ phylogenetic reconstructions and UPGMA
      dendrograms of genetic similarity of the individuals and combined populations
      were constructed. Comparative molecular genetic analysis revealed a high genetic
      differentiation between S. undulates, S. dauricus, S. relicts, and S. parryi
      (G(st) = 0.58 to 0.82; D = 0.53 to 1.06), along with a low level of genetic
      differentiation of the subgenera Citellus and Urocitellus (G(st) = 0.33; D =
      0.27), distinguished in accordance with the existing taxonomic systems of the
      genus Spermophilus.

PMID- 18825961
TI  - [The gene pool of the Belgorod oblast population: changes in the endogamy indices
      of district populations with time].
AB  - Changes in the endogamy indices of district populations of the Central Chernozem
      region of Russia during the past 100 years were studied. The size of an
      elementary population in this region increased from that of a rural municipality
      in the mid-20th century to that of an administrative district in the late 20th
      century.

PMID- 18825962
TI  - [Methylation of promoter region of RAR-beta2 gene in renal cell, breast, and
      ovarian carcinomas].
AB  - The protein encoded by RAR-beta (retinoic acid receptor) gene is a member of the
      superfamily, of nuclear receptors of retinoids which are involved in regulation
      of cell differentiation and proliferation. The level of RAR-beta2 mRNA is
      downregulated in a number of cell lines derived from human epithelial tumors.
      Inactivation of the RAR-beta2 gene is associated with methylation of its promoter
      region, which is observed in various carcinomas at a frequency of 30-70%. In
      renal and ovarian tumors, methylation at this region is poorly studied, the data
      being contradictory. We report a high methylation frequency in the gene promoter
      region in RCC (59%, 36/61) and a somewhat lower frequency in EOC (30%, 15/50).
      Methylation frequency in BC (46%, 26/56) is consistent with the published data.
      Significant correlation of methylation frequency in promoter region of RAR-beta2
      gene with RCC progression (P < or = 0.005 by Fisher's exact test) was
      established.

PMID- 18825963
TI  - Frequencies of four genetic polymorphisms in the CYP1A2 gene in Turkish
      population.
AB  - Cytochrome P450 (CYP) 1A2 gene is involved in the metabolic activation of several
      carcinogens and altered metabolization of some clinically used drugs. We aimed to
      investigate the distributions of genetic polymorphisms -3860 (G/A)(CYP1A2*1C) and
      -2467 (T/del)(CYP1A2*1D) in the 5'-flanking region and -739 (T/G)(CYP1A2*1E) and 
      163(C/A)(CYP1A2*1F) in the first intron of the CYP1A2 gene in 110 unrelated
      healthy Turkish volunteers by PCR-RFLP technique. The frequencies of each
      polymorphism in Turkish population were found as 0.04, 0.92, 0.01, 0.27 for
      CYP1A2*1C, CYP1A2*1D, CYP1A2*1E, CYP1A2*1F, respectively. Compared with other
      populations, CYP1A2*1D has been found to be significantly increased in Turkish
      population. On the other hand, in general, the frequencies of the other
      polymorphisms were concordant with those in the Egyptian and Caucasian
      populations, and were different from those in the Japanese, Chinese and Ethiopian
      populations. Our results suggest that due to increased frequency of CYP1A2*1D in
      Turkish population, functional significance of CYP1A2*1D should be evaluated. It
      might be screened to determine the relationship between CYP1A2*1D and CYP1A2
      related drug metabolisms in associated groups.

PMID- 18825964
TI  - CLUM: a cluster program for analyzing microarray data.
AB  - Microarray technology is increasingly being applied in biological and medical
      research to address a wide range of problems. Cluster analysis has proven to be a
      very useful tool for investigating the structure of microarray data. This paper
      presents a program for clustering microarray data, which is based on the so call
      path-distance. The algorithm gives in each step a partition in two clusters and
      no prior assumptions on the structure of clusters are required. It assigns each
      object (gene or sample) to only one cluster and gives the global optimum for the
      function that quantifies the adequacy of a given partition of the sample into k
      clusters. The program was tested on experimental data sets, showing the
      robustness of the algorithm.

PMID- 18825965
TI  - [Fine spatial structure of allozyme genotypes in isolated population of
      pedunculate oak Quercus robur L. (Fagaceae)].
AB  - The extent and spatial pattern of genetic variation at polymorphic allozyme loci
      in a population of pedunculate oak Quercus robur from the Bashkir Transural
      region was investigated using autocorrelation analysis. In the plantation
      examined, statistically significant local concentration of most of the alleles in
      two-dimensional space was identified. The measures for protection of this small
      population located outside of the western border of the species range, in the
      mountain--steppe habitat, and characterized by specific gene pool, are suggested.

PMID- 18825966
TI  - Isolation of dinucleotide microsatellite markers in commercially threatened
      Malaysian Mahseer, Tor tambroides.
AB  - Seven single locus dinucleotide microsatellite markers were developed to
      characterize an economically important sport fish and food fish in Malaysia and
      in Southeast Asia. They were obtained by using a rapid method namely the 5'
      anchored PCR enrichment protocol. The specific primers were designed to flank the
      repeat sequences and these were subsequently used to characterize 120 unrelated
      fish from Malaysia and 30 fishes from Indonesia. The number of alleles per locus
      ranged from 2 (SYKVJ1-11) to 6 (SYKVJ1-4) while the levels of heterozygosity
      ranged from 0.0472 (SYKVJ1-11) to 0.7745 (SYKVJ1-2).

PMID- 18825967
TI  - [Expression of imprinted Igf2 and Peg1/Mest genes in postimplantation
      parthenogenetic mouse embryos treated with transforming growth factor alpha in
      vitro].
AB  - The effect of transforming growth factor alpha (TGFt) on the expression of
      imprinted Igf2 and Peg1/Mest genes was studied in diploid parthenogenetic embryos
      (PEs) of (CBA x C57BL/6)F1 mice during the postimplantation period of
      embryogenesis. The PEs were treated with TGFalpha in vitro at the morula stage
      and, after they developed to the blastocyst stage, were implanted into the uterus
      of false-pregnant females. On the tenth day of pregnancy, the PEs were explanted
      for subsequent in vitro culturing for 24 or 48 h. The expression of the imprinted
      Igf2 and Peg1/Mest genes was studied by means of whole mount in situ
      hybridization using digoxigenin-labeled antisense RNAs. The expression of the
      imprinted Igf2 and Peg1/Mest genes was studied in embryos on the tenth day of in
      utero development before culturing and after 24 and 48 h of culturing in vitro.
      The expression of Igf2 before culturing was detected only in the brain of 60% of
      PEs on the tents day of pregnancy (the 21-to 25-somite stages); while the
      Peg1/Mest expression was not detected at all. In control (not treated with
      TGFalpha) PEs, neither gene was expressed at the same 21- to 25-somite stages.
      After 24 h of culturing, the Igf2 expression was detected in the brain of 71% of
      PEs at the 30- to 35-somite stages, while the Peg1/Mest expression was not
      detected. In control (untreated) PEs, neither imprinted gene was expressed at the
      30- to 35-somite stage. After 48 h of culturing, Igf2 was expressed in the
      regions of the brain, developing jaws, heart, liver, and somites of all TGFalpha
      treated PEs at the 40- to 45-somite stages; and Peg1/Mest was expressed in the
      brain, heart, and liver of these embryos. In control (untreated) PEs, neither
      Igf2 nor Peg1/Mest was expressed at these stages The expression patterns of the
      imprinted Igf2 and Peg1/Mest genes in PEs at the most advanced developmental
      stages (40-45 somites) and in normal (fertilized) embryos at the same stages were
      similar; however, their expression rate in PEs was substantially lower than in
      normal embryos. These data indicate that exogenous TGFalpha can reactivate the
      expression of the two imprinted genes, modulating the effects of genomic
      imprinting in such a way that the PE development is improved and substantially
      prolonged.

PMID- 18825968
TI  - [Additional chromosomes in bacteria: properties and origin].
AB  - The review considers papers published over the last 15 years that deal with the
      presence in cells of some bacterial genera and species of a second chromosome
      that is smaller than the major one (occasionally, of two additional chromosomes).
      These additional chromosomes differ from the major one in the set of genes and
      specific features of replication; however, they carry genes vitally important for
      the bacterium. The role of these chromosomes and their probable origin from
      megaplasmids are discussed.

PMID- 18825969
TI  - [Respiratory activity of yeast Yarrowia lipolytica under oxidative stress and
      heat shock].
AB  - Heat shock (45 degrees C) and the effect of oxidants (H2O2) resulted in a
      decrease of the respiratory activity of yeast cells and their survival rate.
      Increased resistance to stress effects after mild heat treatment (37 degrees C)
      or treatment with a nonlethal dose of oxidants (0.5 mM H2O2 for 60 min) was
      accompanied by appearance of an alternative (cyanide-resistant) oxidative pathway
      in the mitochondria, which promotes survival due to retention of the capacity for
      ATP synthesis in the first coupling point at the level of endogenous NADH
      dehydrogenase. The alternative oxidative pathway is more resistant to the effect
      of stressors that disrupt electron transfer in the cytochrome site of the
      respiratory chain.

PMID- 18825970
TI  - [Activity of NAD-dependent isocitrate dehydrogenase, isocitrate lyase, and malate
      dehydrogenase in Mucor circinelloides var. lusitanicus INMI under different modes
      of nitrogen supply].
AB  - The growth and morphology as well as lipogenesis and activity of the enzymes of
      the tricarboxylic acid cycle and the glyoxylate cycle were studied in the fungus
      Mucor circinelloides var. lusitanicus INMI grown at various concentrations of
      urea (nitrogen source) added to the medium in different modes. It was shown that
      the maximum lipid content in the biomass was observed at a low (0.5 g/l)
      concentration of the nitrogen source, whereas the highest content of gamma
      linolenic acid in the lipids was detected at high (up to 4.0 g/l) concentrations
      of the nitrogen source. It was found that, when the feed-batch mode of nitrogen
      supply was used, the amount of gamma-linolenic acid in total fatty acids was
      higher (up to 35%) than in the case of a single administration of the same amount
      of nitrogen source to the medium. The differences in the fatty acid composition
      and the unsaturation degree of the lipids from different subcellular fractions
      were demonstrated. The mycelium from the culture grown after a single
      administration of the nitrogen source was deformed to a great extent. The
      activities of the TCA cycle enzymes, NAD-dependent isocitrate dehydrogenase
      (IDH), and malate dehydrogenase (MDH) were lower than in the case of the feed
      batch mode of urea addition, whereas the activity of isocitrate lyase (ICL), the
      key enzyme of the glyoxylate cycle, was higher. The coupling of the cell
      metabolism and the lipid composition of fungal cells and the process of cell
      differentiation in fungi depending on the conditions of nitrogen supply is
      discussed.

PMID- 18825971
TI  - [Metabolic characteristics and lipid composition of yeastlike cells and mycelium
      of Mucor circinelloides var. lusitanicus INMI grown at a high glucose content in
      the medium].
AB  - It is shown that the fungus Mucor circinelloides var. lusitanicus INMI grown
      under aerobic conditions in a medium with a high glucose concentration (20%) is
      capable of both yeastlike and mycelial growth. In the mycelium, the activity of
      NAD-dependent isocitrate dehydrogenase was more than twice as high as in
      yeastlike cells, whereas the isocitrate lyase activity was lower. A number of
      significant differences were found in the lipid composition of the cells of two
      different morphological variants. Yeastlike cells contained more polar lipids and
      free fatty acids and less principal reserve lipids (triacylglycerides) than
      mycelial cells; the content of gamma-linolenic acid and the degree of lipid
      unsaturation were significantly lower in these cells than in the mycelium. In
      yeastlike cells, glycolipids composed the bulk of polar lipids; the proportion of
      phospholipids (primarily phosphatidylserine, phosphatidylcholine,
      phosphatidylethanolamine, and cardiolipin) was lower. The relationship between
      cellular metabolism and the lipid composition of fungal cells of different
      morphotypes grown at high concentrations of glucose, one of the main inducers of
      dimorphic growth, is discussed.

PMID- 18825972
TI  - [Transport systems for carbonate in the extremely natronophilic cyanobacterium
      Euhalothece sp].
AB  - The effect of carbonate concentration, pH of the medium, and illumination
      intensity on the major physiological characteristics (growth rate and the
      intensities of CO2 assimilation and oxygen photoproduction) of the natronophilic
      cyanobacterium Euhalothece sp. Z-M001 have been studied. It was established that
      the investigated microorganism has at least two transport systems (TS) for CO2,
      which differ in both the pH optimum and substrate affinity: TS I has a pH, 9.4
      9.5 and a K(S) 0.5 of 13-17 mM, whereas TS II has a pH(opt) 9.9-10.2 and a K(S)
      0.5 of 600-800 mM. The substrate affinity of these transport systems is several
      orders of magnitude lower than the substrate affinity of the transport systems of
      freshwater cyanobacteria. It is suggested that they are unique for extremely
      alkaliphilic cyanobacteria and reflect their adaptation to the seasonal cycles of
      the lake hydrochemistry.

PMID- 18825973
TI  - [Alkaliphilic sulfidogenesis on cellulose by combined cultures].
AB  - Soda lakes are characterized by an intense sulfur cycle that begins with
      sulfidogenesis. Model laboratory experiments that involved combining of pure
      cultures showed that, during anaerobic decomposition of cellulose by Clostridium
      alkalicellulosi, the sulfate-reducing bacteria (SRB) of the species
      Desulfonatronovibrio hydrogenovorans, Desulfonatronum lacustre, and
      Desulfonatronum cooperativum, different in their nutritional requirements, may
      directly use the cellulose fermentation products for sulfidogenesis without
      mediatory microorgansims. In binary cocultures with SRB, the amount of the H2S
      formed constituted from one-third to two-thirds of the cellulose [H] equivalents;
      acetate was among the products formed. When the syntrophic Contubernalis
      alkalaceticum, capable of acetate oxidation, was incorporated into the trophic
      chain along with hydrogenotrophic SRB, the amount of the H2S formed exceeded by
      33-42% the amount of the [H] equivalents in the utilized cellulose, water being
      the source of additional hydrogen. Thus, the trophic pathway from plant residues
      to sulfide, previously considered to be the longest in the alkaliphilic microbial
      community, may involve a minimal number of stages and do without intermediate
      participation of dissipotrophic fermenters.

PMID- 18825974
TI  - [Effect of vitamin concentration on the synthesis of lactate, ethanol, pyruvate,
      and ethyl acetate in cells of the yeast Dipodascus magnusii].
AB  - In the yeast Dipodascus magnusii, which is auxotrophic for thiamine and biotin,
      during cultivation on glucose with excessive thiamine concentration, pyruvate
      metabolism was shown to result in the synthesis of fermentation products, namely,
      ethanol and, to a lesser extent, lactate. Substantial synthesis of ethyl acetate
      was also observed under these conditions. Introduction of nicotinic acid (NA)
      into the medium resulted in time separation of ethanol and lactate production. It
      was shown that cultivation of the yeast under biotin deficiency resulted in
      nearly complete suppression of aerobic production of ethanol and cessation of
      ethyl acetate synthesis, whereas lactate synthesis was activated as early as in
      the first hours of cultivation. Upon introduction of NA under these conditions,
      lactate concentration sharply increased. These results show that the combination
      of thiamine and biotin with other vitamins can stimulate utilization of the
      pyruvate pool in yeasts towards formation of considerable amounts of lactate,
      which is typical only of cells of higher eukaryotes and bacteria.

PMID- 18825975
TI  - [Characterization of an extracellular glycolipid from Lentinus edodes (Berk.)
      Sing [Lentinula edodes (Berk.) Pegler]].
AB  - Submerged mycelium of a xylotrophic basidiomycete Lentinus edodes produces an
      extracellular glycolipid, S3, associated with a lectin. Galactose glycan residue,
      as well as the lipid pool composition, which includes nonhydroxylated short-chain
      fatty acids, is uncommon for basidiomycetes. The glycolipid consists of D
      galactopyranose (15% of S3 contains galactose sulfate) acylated by octadecanoic
      and nonadecanoic fatty acid residues (28 and 72%, respectively). The glycolipid
      structure and composition are confirmed by physicochemical analysis. The
      glycolipid is assumed to be a regulator of lectin activity.

PMID- 18825976
TI  - [Intracellular lectins of Lentinus edodes at various developmental stages of the
      fungus].
AB  - A number of lectins varying in polypeptide composition and carbohydrate
      specificity were isolated from Lentinus edodes at different stages of its
      morphogenesis: nonpigmented mycelium, brown mycelium film, and fruiting body.
      Three lectins were identified at the nonpigmented mycelium stage, two of them
      being dimers consisting of 16 and 45 kDa and 16 and 42 kDa subunits; the third is
      a tetramer of 16, 39, 42, and 45 kDa subunits. The fractions with lectin activity
      obtained at the brown mycelium film stage contained polypeptides of 24, 30, and
      38 kDa, characteristic of this morphological structure. The fruiting body was
      shown to contain two lectins of 43 and 55 kDa. All of the isolated lectins
      expressed the highest affinity towards L,D-melibiose, D-lactose, and D-galactose.

PMID- 18825977
TI  - [Growth and biosynthesis of rugulovasines in Penicillium variabile Sopp 1912].
AB  - Production of clavine alkaloids rugulovasines by P. variabile did not depend on
      the habitat of the producers. During submerged cultivation on a simple synthetic
      medium in early growth stages, microcyclic conidiation was observed in the tested
      fungi; its presence or absence, as well as the activity of the cultures as to
      biosynthesis of rugulovasines, depended on the composition of the culture medium.
      On a complex medium supplemented with peptone, conidiation occurred but was
      considerably suppressed. Conidia were completely absent in the medium
      supplemented with yeast extract. In both cases, no appreciable amounts of
      rugulovasines were detected.

PMID- 18825978
TI  - [Marine fungus Stilbella aciculosa as a potential producer of prostaglandins].
AB  - The amount and composition of fatty acids in the fungus Stilbella aciculosa
      associated with the marine macroorganism Apostichopus japonica (trepang) were
      determined by gas-liquid chromatography and gas chromatography-mass spectrometry.
      In the culture liquid of S. aciculosa, prostaglandins (PG) of groups E and F were
      revealed by UV spectroscopy. This finding was confirmed by the presence of direct
      precursors of PG, polyunsaturated eicosapentaenoic and docosahexaenoic acids, in
      the culture liquid. The biomass of this fungus contained PG of group B.

PMID- 18825979
TI  - [Structural and physiological diversity among cystlike resting cells of bacteria
      of the genus Pseudomonas].
AB  - Cystlike resting cells (CRC) of non-spore-forming gram-negative bacteria of the
      genus Pseudomonas, P. aurantiaca and P. fluorescens, were obtained and
      characterized for the first time; their physiological and morphological diversity
      was demonstrated. The following properties were common for all the revealed types
      of CRC as dormant forms: (1) long-term (up to 6 months or longer) maintenance of
      viability in the absence of culture growth and cell respiration; (2) absence of
      an experimentally detectable level of metabolism; (3) higher resistance to damage
      and autolysis under the action of provoking factors than in metabolically active
      vegetative cells; and (4) specific features of ultrastructural organization
      absent in vegetative cells: thickened and lamellar envelopes, clumpy structure of
      the cytoplasm, and condensed DNA in nucleoid. The differences in various types of
      CRC concern the thickness and lamellar structure of cell envelopes, as well as
      the presence and thickness of the capsular layer. In particular, forms
      ultrastructurally similar to typical bacterial cysts were revealed in pseudomonad
      populations growing on soil agar. Physiological diversity was revealed in
      different levels of viability preservation and thermal resistance in various
      types of CRC and depended on the conditions of their formation. The optimal
      conditions and procedures for obtaining P. aurantiaca and P. fluorescens CRC that
      retain the ability to form colonies on standard nutrient media are as follows:
      (1) a twofold decrease of nitrogen content in the growth medium; (2) an increased
      level of anabiosis autoinducer (C12-AHB, 10(-4) M) in stationary cultures; (3)
      transfer of the cells from stationary cultures to a starvation medium with
      silica; (4) cultivation in soil extract; and (5) development of cultures on soil
      agar. The CRC from the cultures grown in soil extract or starvation medium with
      silica proved to be resistant to heat treatment (60 degrees C, 5 min). In the CRC
      formed in nitrogen-limited media, the degree of heat resistance increased at
      longer incubation (1.5 to 6 months). CRCs on soil agar surface were resistant to
      desiccation. The ultrastructure of the morphologically varied types of P.
      aurantiaca CRC formed under simulated natural conditions is described for the
      first time. The data on the intraspecies diversity of pseudomonad dormant forms
      contribute to the concept of plasticity of the life style and adaptive reactions
      that ensure survival of these bacteria in unfavorable environmental conditions.

PMID- 18825980
TI  - The primary structure and characteristics of the ISAfe600, an insertion sequence
      from Acidithiobacillus ferrooxidans strains.
AB  - A new IS-like element (604 bp) was revealed in the genome of several
      Acidithiobacillus ferrooxidans strains isolated from diverse biotopes. It
      includes 26-bp imperfectly matched terminal inverted repeats (TIRs), similar in
      structure to the TIRs of ISAfel insertion element. The 60-bp DNA fragment
      adjacent to the right TIR (TIRR) exhibits pronounced homology with the similarly
      located DNA fragments in ISAfel and IST445, as well as with the internal fragment
      of ISAfel encoding the transposase gene (nucleotides from 254 to 311 bp). The
      central section of ISAfe600 is unique and exhibits no homology with any
      prokaryotic DNA. A duplication of 8 bp of the target DNA was found in the
      ISAfe600 insertion site. One to four copies of ISAfe600 were revealed by Southern
      hybridization in the genome of A. ferrooxidans strains studied. The number of
      ISAfe600 copies varies depending on the growth conditions (energy substrate).
      Since the open reading frames big enough to encode transposase are not presert in
      the structure of ISAfe600, it may be a deficient IS element; its translocation is
      possibly achieved under control of the ISAfel transposase.

PMID- 18825981
TI  - [Characterization of yeast groupings in the phyllosphere of Sphagnum mosses].
AB  - Significant differences were revealed in the taxonomic structure of the epiphytic
      yeast communities formed on Sphagnum mosses and on the leaves of vascular plants.
      On mosses, low abundance of red yeasts was found (the most typical epiphytes on
      vascular plant leaves), along with a relatively high content and diversity of
      nonpigmented dimorphic basidiomycetes related to the order Leucosporidiales. The
      species composition of epiphytic yeasts from mosses is different from that of
      both forest and meadow grasses and of the parts of vascular plants submerged in
      the turf. The specific composition of the Sphagnum mosses yeast community is
      probably determined by the biochemical characteristics of this environment,
      rather than by the hydrothermal regime in the turf.

PMID- 18825982
TI  - [The structure of micromycete complexes in permafrost and cryopegs of the
      Arctic].
AB  - A comparative study of the structure of micromycete complexes has been performed.
      The samples of micromycetes were taken by boring from unique habitats: cryopegs
      (lenses of non-freezing hypersaline water in ancient permafrost horizons) and
      permafrost Arctic sediments of different age enclosing these cryopegs. The
      possibility of characterizing the above habitats by the structure of specific
      complexes of microscopic fungi using qualitative and quantitative indices at
      extremely low numbers of these organisms was demonstrated.

PMID- 18825983
TI  - [A laboratory model of the cyanobacterial mat from the Kotel'nikovskii hot spring
      (Baikal Region)].
AB  - A laboratory model of the cyanobacterial community of the Kotel'nikovskii hot
      spring (Baikal Region) was developed. A step-by-step description of the
      algocenosis formation along both the time and temperature gradient was given. The
      natural and laboratory mats were compared, and the major differences in the
      qualitative and quantitative composition of the cyanobacterial community were
      revealed. The laboratory algocenosis was stratified by species composition and
      was characterized by rapid replacement of the dominant cyanobacterial species
      depending on the temperature gradient. The formation of the community structure
      occurred over the 18 days of the experiment. In space and time, the sequence of
      species emergence in the cyanobacterial mat was as follows: Mastigocladus
      laminosus --> Phormidium tenue --> Ph. ambiguum --> Ph. valderiae. The species
      composition of the laboratory mat was similar to that of the natural mat; however
      it was found to be less diverse.

PMID- 18825984
TI  - [Distribution and characteristics of Bacillus bacteria associated with
      hydrobionts and the waters of the Peter the Great Bay, Sea of Japan].
AB  - Bacilli of the species Bacillus subtilis, B. pumilus, B. mycoides, B. marinus and
      B. licheniformis (a total of 53 strains) were isolated from 15 invertebrate
      species and the water of the Vostok Bay, Peter the Great Bay, Sea of Japan.
      Bacilli were most often isolated from bivalves (22.7%) and sea cucumbers (18.9%);
      they occurred less frequently in sea urchins and starfish (13.2 and 7.5%,
      respectively). Most of bacilli strains were isolated from invertebrates
      inhabiting silted sediments. No Bacillus spp. strains were isolated from
      invertebrates inhabiting stony and sandy environments. The species diversity of
      bacilli isolated from marine objects under study was low. Almost all bacterial
      isolates were resistant to lincomycin. Unlike B. pumilus, B. subtilis isolates
      were mostly resistant to benzylpenicillin and ampicillin. Antibiotic sensitivity
      of B. licheniformis strains was variable (two strains were resistant to
      benzylpenicillin and oxacillin, while one was sensitive). A significant fraction
      of isolated bacilli contained pigments. Pigmented strains were more often
      isolated from seawater samples, while colorless ones predominated within
      hydrobionts. B. subtilis colonies had the broadest range of colors. In the
      Bacillus strains obtained, DNase, RNase, phosphatase, elastolytic, chitinase, and
      agarolytic activity was detected. Bacilli strains with hydrolytic activity
      occurred in invertebrates more often than in seawater.

PMID- 18825985
TI  - [Use of enrichment cultures for assessing the structure of methanotrophic
      communities in peat soil: the problem of representativity of the results].

PMID- 18825986
TI  - [Radiobiological analysis of cancerogenic risk values in radioepidemiological
      investigations].
AB  - The aim of the present article consisted in critical analysis of the
      epidemiological approach to radiocancerogenic risk estimation in region of low
      level radiation (LLR). The estimation is making by means of mathematician models
      that ignore a principal difference in biological action of LLR and high level
      radiation (HLR). The main formal characteristic of LLR action is the presence of
      a plateau in beginning of a dose-effect curve of radiogenic risk. It may be
      argued by the following positions: repeating the plateau-phenomenon on various
      radiobiological effects, in different tests and bioobjects, first; a paradoxical
      trend of reciprocal ERR/Sv increasing regarding dose decreasing in region of
      plateau, second, and third, the increasing of the curvature in dose-effect curve
      beginning. The presence of a plateau is associated with the presence of a real
      radiogenic risk threshold. Besides, the analysis of processes influencing
      significantly the dynamics of initial radiation injury of biologically important
      macromolecules showed the preference in region of LLR those,
      decreasing/eliminating genome damages. There is follows from mentioned above a
      necessity to evaluate radiogenic risks in LLR region separately from HLR region.

PMID- 18825987
TI  - [The alteration of attractiveness of intact males mice to females chemosignals,
      subjected of ionizing radiation in sublethal dose].
AB  - After irradiation in a dose 4 Gy female mice of CBA and C57Bl/6 (female CBA
      during 18-23 days, female C57Bl/6 - 4-10 days) secretes with urine volatile
      components (chemosignals) which possess higher, than secretes intact females,
      attractiveness for intact males the same strains irrespective of a genotype. When
      estimation relative attractiveness postradiation secretes female mice CBA and
      C57Bl/6 intact males prefer chemosignals singenic (genetically identical) females
      during 1-23 day after irradiation. Observed olfactorial reaction male mice more
      differ from norm. In which males prefer chemosignals of allogenic (with a strange
      genotype) females. This disturbances identifed as postradiation reversion
      attractiving males of chemosignals, dependent on the genotype of females. Typical
      for norm chemosignalisation at females restored for 43 days after the
      irradiation. The mechanism and biological advisability of this phenomenon are
      discussed.

PMID- 18825988
TI  - [Leptinotarsa decemlineata Say sensitivity to ionizing radiation and pesticides].
AB  - The effects of acute gamma-irradiation on the Colorado potato beetle
      (Leptinotarsa decemlineata Say) and sensitivity of insects, long time exposed on
      radioactively contaminated territories, to pesticides were studied. LD50 values
      of insects to ionizing radiation during the ontogenesis process was shown to
      increase (from 8 to 48 Gy). Differences were noted in the development rates of
      the natural population of beetles collected on agricultural lands with 137Cs
      contamination density of 0.05-1.2 MBq/m2, with the sensitivity to various
      pesticide groups being the same.

PMID- 18825989
TI  - [Radiobiological effects on plants and animals within Semipalatinsk Test Site
      (Kazakhstan)].
AB  - The Semipalatinsk Test Site (STS) was the main place of nuclear devices tests in
      the former Soviet Union. From 1949 to 1989 about 460 nuclear explosions have been
      carried out at STS. Radioactive contamination of STS territory has the extremely
      non-uniform character. The main dose-forming radionuclides are 137Cs, 90Sr,
      152Eu, as well as 154Eu, 60CO, 239,240Pu and 241Am. The greatest specific
      activity of 137Cs and 239,240Pu in ground are n x 10(3) kBk/kg, 152Eu - 96
      kBk/kg, 154Eu - 10.4 kBk/kg, 60Co - 20.5 kBk/kg, 241Am - 15 kBk/kg. However, up
      to now, within STS sites exists where gamma-dose rate comes to 60 microGy/h, that
      is enough for induction reliable biological effects in animals and plants.
      Inhabiting territory of STS plants and animals are characterized by increased
      level of mutagenesis, changes of morpho-anatomic indices and parameters of
      peripheral blood, by the increase of asymmetry bilateral indices, change of
      composition and structure of communities.

PMID- 18825990
TI  - [The dose estimation of woody plants in the long-term after the Chernobyl NPP
      accident].
AB  - Dosimetric models have been developed to estimate the exposure doses of woody
      plants growing in the area contaminated by long-lived radionuclides. The models
      are parameterized based on the data obtained from the experimental plots in the
      south-west districts of the Bryansk region affected by radioactive fallout of the
      Chernobyl NPP accident. Doses are estimated to generative organs of pine trees
      from these plots. The contribution from various sources and types of ionizing
      radiation to the absorbed dose formation for these objects is determined.

PMID- 18825991
TI  - [The evaluation of association between polymorphisms of DNA excision repair
      enzyme genes and risk of malignant tumors development in Siberian Group of
      Chemical Enterprises workers].
AB  - There was analyzed single nucleotide polymorphisms of DNA excision repair enzyme
      genes hOGG, XPD, XPG, XRCC1 in 98 Siberian Group of Chemical Enterprises cancer
      patients and 148 healthy donors. No association was observed between the analyzed
      polymorphisms and malignant tumors in both control and subgroup (under study) of
      persons exposed to occupational ionizing radiation. Heterozygosis for the genes
      hOGG and XPD was found to be a protective factor to malignant tumors in exposed
      persons: the odds ratio = 0.42 (95% CI 0.18-0.98; p = 0.044) for the 326Ser/Cys
      genotype of the hOGG gene and 0.48 (95% CI 0.23-0.99; p = = 0.047) the 751Lys/Gln
      genotype of the XPD gene. The data obtained show a possible modifying role of the
      hOGG and XPD gene polymorphisms for malignant tumors risk in exposed persons.

PMID- 18825992
TI  - [Risk factors prevalence for cardiovascular diseases among atomic power industry
      enterprises personnel].
AB  - A selective cross-sectional study based on Regional Medico-Dosimetric Register
      was carried out in some Siberian Group of Chemical Enterprises (SGCE) workers
      (aged 40-50) with the aim of studying the most important risk factors prevalence
      for cardiovascular diseases development. 2010 persons examined with the use of
      standardized epidemiological methods made up 32.6% of total SGCE personnel aged
      40-50. PURPOSE: the study of risk factors of cardiovascular diseases, their
      prevalence, intensity and significance in atomic power plants workers exposed to
      occupational long-term ionizing radiation in a "low" dose range (cumulative doses
      in the range up to 1 Sv). The study of prevalence of risk factors for CVDs
      development in men occupationally exposed to ionizing radiation revealed frequent
      changes in the type of work performed, higher levels of psychoemotional tension,
      as well as high prevalence of low levels of high-density lipoprotein cholesterol
      (HDL-cholesterol) and obesity. Women workers of the main production were found to
      have hypercholesterolaemia more often than those of the auxiliary production.
      Annual health checks of nuclear workers should be extended to include waist and
      hips measurement, body mass index (BMI) calculation, lipid factors evaluation, as
      well as stress tests (bicycle and/or stress echocardiography) in case there are
      three or more risk factors for CVDs for workers of the main production.

PMID- 18825993
TI  - [The risk of arterial hypertension development in Siberian Group of Chemical
      Enterprises personnel].
AB  - PURPOSE: to study risk factors of arterial hypertension (AH), their significance
      for AH pathogenesis in atomic power plants employees occupationally exposed to
      long-term ionizing radiation in a "low" dose range (cumulative external radiation
      doses in the range up 1 Sv). The case-control study was carried in the cohort of
      workers aged 40-50 ever employed at the Siberian Group of Chemical Enterprises
      (SGCE) between 2003-2005. 970 persons were examined by standardized
      epidemiological methods. "Case" (n = 359) was found to be a recent AH case (less
      than 3 years) in SGCE employees whose average length of service is 3 years.
      "Control" (n = 611) - healthy men of the same age, length of service and working
      conditions. Risk of AH development (odds ratio (OR) = 1.6 (1.1; 2.37) was found
      to be higher in radiation workers in comparison with non-radiation ones without
      any linear dependence of risk upon cumulative external gamma-radiation dose in
      the range under study (OR in a cumulative external radiation dose range 7.3-21.3
      mSv = 1.6 (0.96; 2.51); OR in a cumulative external radiation dose range 21.4
      68.5 mSv = 1.7 (1.04; 2.67); OR in a cumulative external radiation dose range
      68.6-864 mSv = 1.6 (1.01; 2.57). Not only traditional risk factors such as:
      obesity (OR = 7.1 (5.06; 10.1), frequent alcohol usage (OR = 1.3 (1.06; 1.63)),
      dyslipidemia (OR = 2.1 (1.61; 2.08)); hyperhomocisteinemia (OR = 1.4 (1.09;
      1.72)); psychoemotional (OR = 1.4(1.11; 1.89)), hereditary aggravation (OR = 2.2
      (1.75; 2.9)) in SGCE personnel, but also technogenic explosion descriptions are
      related to AH development. The long-term occupational external gamma-radiation in
      a dose range up 1 Sv potentiates a negative influence of CVD traditional risk
      factors (for hypercholesterinemia OR = 1.9 (1.3; 2.9), for AH OR = 3.1 (2.2;
      4.6)) that leads to increase in risk coefficients for 30-60% in persons exposed
      to traditional and technogenic factors impact (for hypercholesterinemia and
      ionizing radiation OR = 2.5 (1.7; 3.2); for AH and IR OR = 3.9 (2.8; 5.2)) in
      comparison with non-radiation personnel.

PMID- 18825994
TI  - [Adaptive response--the general biological tendency: facts, hipothesis,
      questions].
AB  - It is leading up to the proofs testifying about the general-biological nature of
      adaptive response (AR), which is similar unspecific defense effect: for example,
      small doses induce cytokines synthesis, providing the resistance to different
      infectious agents. The connection between AR, DNA-repair, anti-oxidative status,
      expression of TP53 gene is discussed. The absence of AR at some patients can be
      explained either individual sensitivity to challenging treatment or criteria of
      the estimation (chromosome aberration, apoptosis et. al.). These facts are
      showing that the absence of AR cannot be the indicator of the risk for health. So
      the idea about general biological existence of AR is postulated because it is a
      characteristic for different species.

PMID- 18825995
TI  - [Biological effects of electromagnetic radiation of extremely high frequencies
      combined with physiologically active compounds].
AB  - The study of the action of the electromagnetic radiation (EMR) of low intensity
      (10 microW/cm2) in the range of frequencies 120-170 GHz at the test-reaction of
      Infusoria Paramecium caudatum was carried out. The resonant character of the
      effects was established. The EMR action at 156.6 and 161.3 GHz caused the
      increase of infusorians mobility, the action at frequencies 151.8, 155.7, 167.1
      GHz caused the mobility reduction. Isolated and combined with EMR effects of
      nicotine (10(-4)-10(-15) mol/l) and antimicrobial drug metronidazole (10(-5), 10(
      8), 10(-9) mol/l) were investigated. The radiation at the frequency 167.1 GHz was
      shown to reduce the effect of nicotine (10(-9) mol/l) and to enhance the effect
      of metronidazole (10(-9) mol/l). This phenomenon may be explained by different
      effects of the substances in low concentration at the water hydrogen bonds net
      structure.

PMID- 18825996
TI  - [The stability of enzyme activity and the content of microflora of different
      soils of the South of Russia to influence of a variable magnetic field of
      industrial frequency].
AB  - In modelling experiments of the influence of variable magnetic field of
      industrial frequency (50 Hz) by induction of 1500 and 6000 mkTl during 5 days on
      microflora and on enzyme activity of soils the South of Russia of different
      genesis and properties is investigated.

PMID- 18825997
TI  - [The effects of UV-irradiation of barley plants on the morphophysiological
      parameters and productivity of the offsprings].
AB  - In a greenhouse experiment effects have been studied the UV-B-irradiation of
      barley (intensity of biologically active UV-B-radiation was 0.15, 0.29 and 0.45
      W/m2) on the morphophysiologic parameters, productivity and reproductive sphere
      of offsprings of two succeeding generations. It has been shown that along with a
      decrease in the specific leaf mass and biomass M1-generation plants exhibited an
      increase in the stem height and assimilative leaf area. The reduction of grain
      yield in offsprings of the first post-radiation generation was mainly caused by
      the reduced size in the reproductive organs and by reduced number of caryopsides
      in a ear. The observed effects were independent of the UV-B exposure levels to
      the precursors. The aftereffect of UV-B-irradiation for M2-generation plants
      shown itself as changes in the specific leaf area, less pronounced compared to
      the precursors, and reduction in the vegetative mass and grain yield, most
      significant in offsprings of plants exposed to the maximum UV-B levels.
      Disturbances in the reproductive sphere appeared as reduction in the size of
      developing grains. The data derived suggest that long-term effects of UV-B
      irradiation are possible not only in the first but also in the second generation
      of impacted plants.

PMID- 18825998
TI  - [The estimation of ionizing irradiation impact on Vicia cracca cenopopulations
      growing on the territory contaminated with the wastes of radium production].
AB  - The radiation exposure on cenopopulations Vicea cracca L. growing on the
      territory contaminated with the wastes of radium production was estimated. The
      relationship between the chromosome aberration in seedlings root tip cells and
      irradiation dose was found to be linear. The significant cytogenetic effects in
      chronically irradiated Vicia cracca cenopopulation are observed at doses (equal
      to 0.006-0.7 Gy) 10 times upward the natural radiation background level. The
      reduced reproductive success (significantly increased embryonic lethal mutation
      level) is observed at weighted absorbed doses (equal to 0.2-0.7 Gy) up to 200-700
      times higher than the natural radiation background level. It is showh, that the
      radiation hygienic standards of permissible exposure are noticeably stricter that
      the radioecological limits.

PMID- 18825999
TI  - [The investigation of the composition of liquid radioactive waste].
AB  - In investigation the process of composition sediment of liquid unorganic
      radioactive waste, that are forming in cistern-selectors at PNPI RAS, it was
      discovered apart from great quantity of ions of different metals and
      radionuclides considerable maintenance of organic material (to 30% and more from
      volume of sediment) unknown origin. A supposition was made about its
      microbiological origin. Investigation shows, that the main microorganisms,
      setting this sediment, are the bacterious of Pseudomonas kind, capable of
      effectively bind in process of grow the radionuclide 90Sr, that confirms the
      potential posibility of using this microorganisms for bioremediation of liquid
      low radioactive wastes (LRW).

PMID- 18826000
TI  - Determinants of the choice of health care provider in Nigeria.
AB  - The study investigated the determinants of households' choice of health care
      provider in Nigeria. Individual and household based questionnaires were used for
      the study. Using a multinomial logit model, the findings revealed that both
      distance and money prices are significant factors in discouraging individuals
      from seeking modem health care services but money prices was less important as a
      determinant of the choice of health care provider. And from the descriptive
      analysis, money price was a major reason why many low income households opted for
      the self-care option. Furthermore, the study showed that older people tend to
      patronize public and private hospitals.

PMID- 18826001
TI  - Operating room management and operating room productivity: the case of Germany.
AB  - We examine operating room productivity on the example of hospitals in Germany
      with independent anesthesiology departments. Linked to anesthesiology group
      literature, we use the ln(Total Surgical Time/Total Anesthesiologists Salary) as
      a proxy for operating room productivity. We test the association between
      operating room productivity and different structural, organizational and
      management characteristics based on survey data from 87 hospitals. Our empirical
      analysis links improved operating room productivity to greater operating room
      capacity, appropriate scheduling behavior and management methods to realign
      interests. From this analysis, the enforcing jurisdiction and avoiding advance
      over-scheduling appear to be the implementable tools for improving operating room
      productivity.

PMID- 18826002
TI  - Restructuring routine elective services to reduce overall capacity requirements
      within a local health economy.
AB  - The U.K. Government has introduced a new class of health service providers called
      Treatment Centres that provide routine elective services but that do not deal
      with emergency cases or non-routine elective patients. The introduction of these
      centres provides a possible mechanism for improving the efficiency of service
      delivery in terms of overall capacity requirements. In this paper we discuss a
      mathematical modelling approach that has been used to examine circumstances under
      which such benefits might be realised. As an illustration of the analysis, we
      present results obtained using data concerning urological services, for which
      there would seem to be benefits associated with the introduction of a TC in only
      a limited range of circumstances.

PMID- 18826003
TI  - A queueing network model to analyze the impact of parallelization of care on
      patient cycle time.
AB  - The total time a patient spends in an outpatient facility, called the patient
      cycle time, is a major contributor to overall patient satisfaction. A frequently
      recommended strategy to reduce the total time is to perform some activities in
      parallel thereby shortening patient cycle time. To analyze patient cycle time
      this paper extends and improves upon existing multi-class open queueing network
      model (MOQN) so that the patient flow in an urgent care center can be modeled.
      Results of the model are analyzed using data from an urgent care center
      contemplating greater parallelization of patient care activities. The results
      indicate that parallelization can reduce the cycle time for those patient classes
      which require more than one diagnostic and/ or treatment intervention. However,
      for many patient classes there would be little if any improvement, indicating the
      importance of tools to analyze business process reengineering rules. The paper
      makes contributions by implementing an approximation for fork/join queues in the
      network and by improving the approximation for multiple server queues in both low
      traffic and high traffic conditions. We demonstrate the accuracy of the MOQN
      results through comparisons to simulation results.

PMID- 18826004
TI  - Optimal ambulance location with random delays and travel times.
AB  - We describe an ambulance location optimization model that minimizes the number of
      ambulances needed to provide a specified service level. The model measures
      service level as the fraction of calls reached within a given time standard and
      considers response time to be composed of a random delay (prior to travel to the
      scene) plus a random travel time. In addition to modeling the uncertainty in the
      delay and in the travel time, we incorporate uncertainty in the ambulance
      availability in determining the response time. Models that do not account for the
      uncertainty in all three of these components may overestimate the possible
      service level for a given number of ambulances and underestimate the number of
      ambulances needed to provide a specified service level. By explicitly modeling
      the randomness in the ambulance availability and in the delays and the travel
      times, we arrive at a more realistic ambulance location model. Our model is
      tractable enough to be solved with general-purpose optimization solvers for
      cities with populations around one Million. We illustrate the use of the model
      using actual data from Edmonton.

PMID- 18826005
TI  - A survey on statistical methods for health care fraud detection.
AB  - Fraud and abuse have led to significant additional expense in the health care
      system of the United States. This paper aims to provide a comprehensive survey of
      the statistical methods applied to health care fraud detection, with focuses on
      classifying fraudulent behaviors, identifying the major sources and
      characteristics of the data based on which fraud detection has been conducted,
      discussing the key steps in data preprocessing, as well as summarizing,
      categorizing, and comparing statistical fraud detection methods. Based on this
      survey, some discussion is provided about what has been lacking or under
      addressed in the existing research, with the purpose of pinpointing some future
      research directions.

PMID- 18826006
TI  - Pricing of prescription drugs and its impact on physicians' choice behavior.
AB  - This research presents an analysis of Taiwan's health care market with the focus
      on the pricing of prescription drugs and its impact on physicians' choice
      behavior. Since the advent of Taiwan's national health insurance, with the
      competent authority being Bureau of National Health Insurance (BNHI), hospitals
      are allowed to sell prescription drugs to patients at prices above the purchasing
      prices, so each prescription drug has two prices: one at which drugs are sold to
      hospitals; the other which BNHI reimbursement to hospitals. The margin between
      the different prices is the sales discount that pharmaceutical companies offer to
      the hospitals. We find that sales discount has a great impact on physicians'
      choice behavior: i.e., physicians are price-sensitive to prescription drugs. In
      addition, it is found that too high a sales discount of a prescription drug would
      result in a too low weighted average price of that drug sold; thus BNHI would be
      more likely to adjust downward the rate it reimbursement to the hospital. This
      presents a sales strategy problem to pharmaceutical companies. To solve this, we
      use the distribution of physicians' evaluations of prescription drugs to
      establish a profit maximization model in hopes of helping companies to price
      drugs and find the optimal promotion expending. Ten popular prescription drugs
      are used in this research as examples.

PMID- 18826007
TI  - A technical note concerning non-adherence to drug therapy: exact expressions for
      the mean and variance of drug concentration.
AB  - There is considerable evidence that prescribed drugs are not taken as intended.
      We present a stochastic pharmacokinetic mathematical model that can be used to
      assess the implications of non-adherence to prescribed drug regimens, on the part
      of either patients or health professionals. In the context of an orally
      administered drug, explicit equations are derived for the time varying mean and
      variance of the concentration of the drug in the serum, depending on the
      probability of each scheduled administration being omitted. The analysis
      presented here can be used to assess whether a given level of non-adherence is
      likely to have a clinical impact. The methods used can easily be adapted for use
      in the context of other routes of drug administration.

PMID- 18826008
TI  - Quantifying the impact of non-adherence to drug therapy: a technical note
      concerning an application of a branch and bound algorithm.
AB  - Pharmacokinetic models typically rely on a key assumption that patients take
      their medication as prescribed, whereas this is often not the case. We present a
      branch and bound algorithm that can be used to estimate the time-varying
      probability that, given a specified pattern of nonadherence to a prescribed
      regimen, a patient receives no therapeutic benefit from treatment. Use of this
      algorithm is a much faster method for obtaining this probability than exhaustive
      computation of the relevant probability distribution. The use of this algorithm
      to assess, in quantitative terms, the impact of non-adherence on the
      effectiveness of treatment provides a rational basis for evaluating the potential
      harm to patients.

PMID- 18826009
TI  - Research priorities of the profession.

PMID- 18826010
TI  - Factor structure of the four motor-free scales of the Developmental Test of
      Visual Perception, 2nd edition (DTVP-2).
AB  - INTRODUCTION: Visual-perceptual skills of children are often assessed using the
      Developmental Test of visual Perceptual Skills-2, 2nd Edition (DTVP-2). PURPOSE:
      The factor structure of the four motor-free DTVP-2 subscales was examined.
      METHOD: The scores from a sample of 356 healthy children (171 boys and 185 girls)
      ages 5 to 11 years were used to complete a principal components factor analysis
      of the 4 subscales. RESULTS: The position-in-space subscale had items load on six
      factors. The figure ground subscale had items load on five factors. The visual
      closure scale and form constancy subscales both had four factors. When the four
      DTVP-2 subscales were combined to form one overall motor-free visual perceptual
      scale, the items loaded on 21 factors. CONCLUSION: The DTVP-2 and its four motor
      free subscales exhibited multidimensionality instead of the expected
      unidimensional visual-perceptual constructs.

PMID- 18826011
TI  - Teaching chewing: a structured approach.
AB  - OBJECTIVE: A structured intervention was used to teach chewing to two children
      with special needs. Neither child had a history of chewing or eating high
      textured food. METHOD: The intervention combined oral-motor and behavior
      components to teach chewing. A multiple baseline design was used to evaluate
      treatment effectiveness. RESULTS: Both children improved their chewing skills
      while increasing the texture of foods eaten and the variety of foods eaten.
      CONCLUSION: This structured intervention could be used to teach chewing to a
      range of children who did not acquire this skill during normal development.

PMID- 18826012
TI  - Playful interaction: occupational therapy for all children on the school
      playground.
AB  - We examined the impact of an intervention on the playfulness of 5- to 7-year-old
      children who are developing typically. Materials that had no defined purpose were
      placed on a school playground for 11 weeks. The Test of Playfulness (ToP) was
      used to compare videotaped play segments pre- and postintervention. Teachers who
      did playground duty were interviewed regarding changes in play. ToP data were
      analyzed using a Wilcoxon signed-ranks test. Interview data were analyzed for
      themes. ToP scores were significantly higher after intervention (Z= -1.94; p =
      .025, one-tailed; Cohen's d = 0.55). Teachers reported that children were more
      social, creative, and resilient when the materials were on the playground.
      Children who were creative, rather than very physically capable, became leaders
      in activity. Our results revealed a potential role for occupational therapists
      with typically developing children in schools. This finding has clear
      implications for children with disability.

PMID- 18826013
TI  - Development of a performance assessment of executive function: the Children's
      Kitchen Task Assessment.
AB  - OBJECTIVE: This study developed and explored the validity of the Children's
      Kitchen Task Assessment (CKTA), a performance assessment of executive function.
      METHOD: The development of the CKTA is described. Children were given the CKTA
      and neuropsychological assessments of executive functioning. Parents completed
      the Parent Behavior Rating Inventory of Executive Function (Parent BRIEF).
      RESULTS: Forty-nine typically developing children ages 8 to 12 years participated
      in this study. Interrater reliability and internal consistency were established.
      Preliminary evidence of discriminant validity was reflected in significant
      differences on neuropsychological tests and the Parent BRIEF between high- and
      low-scoring CKTA groups. Age-related differences in CKTA performance further
      supported discriminant validity. Support for concurrent validity was observed in
      moderate correlations with established neuropsychological tests. CONCLUSION:
      Preliminary results suggest the CKTA is a valid performance assessment that
      evaluates the level of cognitive assistance children require to complete a
      challenging functional activity.

PMID- 18826014
TI  - Outcomes of a pilot training program in a qigong massage intervention for young
      children with autism.
AB  - Sensory impairment is a common and significant feature of children on the autism
      spectrum. In 2005, a qigong massage intervention based on Chinese medicine and
      delivered by a doctor of Chinese medicine was shown to improve sensory impairment
      and adaptive behavior in a small controlled study of young children with autism.
      In 2006, the Qigong Sensory Training (QST) program was developed to train early
      intervention professionals to provide the QST intervention. This article
      describes the preliminary evaluation of the QST program as piloted with 15
      professionals and 26 children and outcomes testing using standardized tests of
      sensory impairment and adaptive behavior. Results of outcomes comparing delivery
      by QST-trained therapists with delivery by a doctor of Chinese medicine showed
      that both groups improved and that there was no difference in outcome between the
      two groups. The intervention and training program are described, and implications
      for future research are discussed.

PMID- 18826015
TI  - You can know me now if you listen: sensory, motor, and communication issues in a
      nonverbal person with autism.
AB  - This case report describes an intensive approach to treating autism and provides
      an intersection between a first-person narrative paired with intervention and
      outcomes. In-depth conversations between a person with autism and an occupational
      therapist provide insight into understanding differences and difficulties in
      sensory processing and regulation, praxis, and communication. Individuals with
      autism may be intellectually and emotionally intact but hampered by deficits that
      interfere with the ability to move the body efficiently. These sensorimotor
      deficits underlie the ability to communicate with others and to develop
      relationships. This article illustrates the benefits of an intensive therapeutic
      program designed to address sensory and motor differences underlying
      communication, as well as the vital role the occupational therapist plays in
      addressing these underlying differences to improve functional communication and
      social participation.

PMID- 18826016
TI  - Out-of-school participation patterns in children with high-functioning autism
      spectrum disorders.
AB  - PURPOSE: This study examined differences in out-of-school activity participation
      between typically developing children and those with high-functioning autism
      spectrum disorders (HFASD). METHOD: Children with HFASD, ages 6 to 12 (N = 52),
      and a control group (N = 53) were assessed using the Children's Assessment of
      Participation and Enjoyment and the Social Responsiveness Scale. RESULTS:
      Significant differences were seen in participation between typical and HFASD
      groups in number of activities in which children participate, the numbers of
      individuals with whom they participate, and the variety of environments in which
      they participate. CONCLUSIONS: These findings indicate that out-of-school
      participation is significantly different for children with HFASD than for
      typically developing peers. Findings suggest that social impairment is related to
      some aspects of participation and that addressing social skills in intervention
      could contribute to increased participation in out-of-school activities by
      children with HFASD, which would contribute to their long-term mental and
      physical health.

PMID- 18826017
TI  - Sensory processing and classroom emotional, behavioral, and educational outcomes
      in children with autism spectrum disorder.
AB  - OBJECTIVE: We explored the associations between sensory processing and classroom
      emotional, behavioral, and educational outcomes of children with autism spectrum
      disorder (ASD). METHOD: Twenty-eight children with ASD (with average-range IQ)
      were compared with 51 age- and gender-matched typically developing peers on
      sensory processing and educational outcomes. RESULTS: For children with ASD, the
      Short Sensory Profile scores Underresponsive/Seeks Sensation and Auditory
      Filtering explained 47% of the variance in academic performance, yet estimated
      intelligence was not a significant predictor of academic performance. Significant
      negative correlations were found between (1) auditory filtering and inattention
      to cognitive tasks, (2) tactile hypersensitivity and hyperactivity and
      inattention, and (3) movement sensitivity and oppositional behavior. CONCLUSION:
      A pattern of auditory filtering difficulties, sensory underresponsiveness, and
      sensory seeking was associated with academic underachievement in the children
      with ASD. Children who have difficulty processing verbal instructions in noisy
      environments and who often focus on sensory-seeking behaviors appear more likely
      to underachieve academically.

PMID- 18826018
TI  - Relationship between performance-based and self-reported assessment of hand
      function.
AB  - OBJECTIVE: To examine the relationships between self-reported and performance
      based hand function. METHOD: Thirty participants with hand function limitations
      completed the Manual Ability Measure (MAM-36) and the Upper Extremity Performance
      Test for the Elderly (TEMPA). Participants were categorized into two groups: (1)
      Dominant Hand Affected and (2) Nondominant Hand Affected. Correlations between
      the two assessments were examined. The speed of task execution and TEMPA scores
      were compared between the two groups. RESULTS: A significant correlation was
      found between the MAM-36 and TEMPA Total Functional Rating (p = 0.79, p < .05).
      Significant differences were found in the speed of execution of unilateral tasks
      and the Unilateral Functional Ratings between the two groups. CONCLUSION: The MAM
      36 is a promising assessment tool for measuring a client's perceived hand
      function. However, a performance-based assessment can supplement information
      about the quality and speed of hand-task performance.

PMID- 18826019
TI  - Person-vehicle-environment interactions predicting crash-related injury among
      older drivers.
AB  - OBJECTIVE: The object of this research was to identify interactions among person,
      vehicle, and environment factors associated with crashes and injuries among older
      drivers. METHOD: We quantified risk factors and interactions for 5,744 drivers.
      RESULTS: Women had a high crash risk during mornings (8:00 a.m.-1:00 p.m.; odds
      ratio [OR] = 1.73, confidence interval [CI] = 1.40-2.14) or afternoons (2:00 p.m.
      8:00 p.m.; OR = 1.74, CI = 1.41-2.15); alcohol-related crashes were the least
      likely to occur during mornings (OR = 0.19, CI = 0.12-0.31). The greatest crash
      risk with another vehicle occurred during afternoons (OR = 3.89, CI = 2.41-5.05).
      Injury had interactions with fixed-object crashes (OR = 427, CI = 182.9-998.24),
      no seatbelt (OR = 5.69, CI = 3.90-8.29), female gender (OR = 1.54, CI = 1.67
      1.92), and mornings (OR = 1.40, CI = 1.01-1.94). CONCLUSION: An opportunity for
      crash and injury prevention research and shaping longer-range evaluation policies
      emerged.

PMID- 18826020
TI  - Search performance of healthy adults on cancellation tests.
AB  - Cancellation tests are used extensively to identify visual search deficiencies in
      people with neurologic conditions, but little is known about how healthy adults
      perform on these tests. This study described the performance and types of search
      strategies used by healthy adults to complete cancellation tests from the Brain
      Injury Visual Assessment Battery for Adults. Study participants predominantly
      used structured left-to-right and top-to-bottom linear search patterns regardless
      of the configuration of the visual array. Other search qualities included (1) use
      of the same pattern throughout the search of an array, (2) symmetrical search of
      the array, and (3) rechecking performance on complex arrays. Older adult
      participants took more time to complete the tests than younger adults did.
      Knowing the strategies healthy adults use on cancellation tests enables
      therapists to identify visual search deficiencies in clients and design
      interventions to reestablish normal search strategies in daily occupations.

PMID- 18826021
TI  - Interrater reliability of a new handwriting assessment battery for adults.
AB  - OBJECTIVE: The objective of this study was to develop, pilot, and evaluate the
      interrater reliability of a new Handwriting Assessment Battery for adults.
      DESIGN: Test development included item selection and interrater reliability
      involving two raters. METHOD: The test assessed pen control and manipulation,
      writing speed, and writing legibility. Ten people with brain injury completed the
      test with two occupational therapists independently rating 10 writing samples.
      Results were analyzed for reliability using kappa and intraclass correlation
      coefficients (ICC2,1). RESULTS: Pen control and manipulation subtests showed high
      to perfect agreement (line drawing subtest, kappa = 1.0; dot subtest, kappa =
      0.80). The speed subtest showed perfect agreement (ICC= 1.0). Writing legibility
      showed high agreement for all five subtests (ICC = 0.71-0.83), although a ceiling
      effect was evident for two subtests. CONCLUSION: Although the test showed
      excellent interrater reliability, further reliability and validity testing are
      needed before the test is used clinically.

PMID- 18826022
TI  - Student outcomes in a postprofessional online master's-degree program.
AB  - The outcomes of five cohorts of occupational therapists who completed an online
      postprofessional master's degree program were evaluated. Data on graduates'
      satisfaction with professional skills and status, contribution of the program to
      their satisfaction, and engagement in professional activities since graduation
      were collected using an online survey. Forty-nine of 65 surveys distributed were
      returned (75% response rate). Respondents indicated high levels of satisfaction
      with professional skills and status and high levels of contribution of the
      program to their satisfaction. Respondents also reported participation in a
      variety of professional leadership activities. Results suggest that
      postprofessional graduate-level education is effective in developing advanced
      critical reasoning, reflection, and leadership skills in occupational therapists
      and in facilitating a variety of professional contributions. The online mode was
      effective in delivering the program content. The value of postprofessional
      education to individuals and the profession is discussed.

PMID- 18826023
TI  - The genus Hyalomma: VII. Redescription of all parasitic stages of H. (Euhyalomma)
      dromedarii and H. (E.) schulzei (Acari: Ixodidae).
AB  - The ticks, Hyalomma (Euhyalomma) dromedarii Koch, 1844 and Hyalomma (Euhyalomma)
      schulzei Olenev, 1931, are considered to be the species most closely associated
      with camels. H. dromedarii can behave as a three-, two-, or one-host species,
      with the two-host life cycle seemingly most common. Camels are the main hosts of
      the adults, which also parasitize other domestic animals. Nymphs and larvae can
      use the same hosts, especially camels, as the adults, but can also parasitize
      rodents, leporids, hedgehogs, and birds. H. dromedarii is widely distributed in
      North Africa, the northern regions of West, Central, and East Africa, Arabia,
      Asia Minor, the Middle East, and Central and South Asia. H. schulzei is a two
      host species. Camels are the principal hosts of the adults, with some records
      from cattle and goats, whereas the immature stages infest hares, burrowing
      rodents, and hedgehogs. H. schulzei has a more limited geographic distribution in
      Asia and Egypt than H. dromedarii, and with the exception of southeastern Iran,
      it is a fairly uncommon tick. Among other features that are fairly similar, males
      of H. dromedarii can be distinguished from those of H. schulzei by a narrow,
      subtriangular parma, usually very large subanal shields, and a long dorsal
      prolongation of the spiracular plates. Males of H. schulzei have a broad and
      rectangular parma, paramedian festoons that protrude posteriorly, smaller subanal
      shields, and a very short dorsal prolongation of the spiracular plates. The
      females of H. dromedarii can be distinguished from those of H. schulzei by a
      narrow V-shaped genital aperture compared with a very wide, deep, U-shaped
      genital aperture. Here all the parasitic stages of both species are illustrated
      and redescribed, and characteristics that distinguish the adults from those of
      other closely related species are supplied. Data on their hosts, geographic
      distribution and disease relationships are also provided.

PMID- 18826024
TI  - The ornithodoros (Alectorobius) talaje species group (Acari: Ixodida: Argasidae):
      description of Ornithodoros (Alectorobius) rioplatensis n. sp. from southern
      South America.
AB  - A new species of argasid tick, Ornithodoros (Alectorobius) rioplatensis Venzal,
      Estrada-Pena, & Mangold, is described from larval and adult specimens collected
      in Uruguay. Further specimens from Argentina, Paraguay, and Chile are ascribed to
      the new species. Key distinguishing characters of larvae of the species are the
      number of pairs of dorsal setae (19-20 but typically 20 in O. rioplatensis,
      compared with 16-17 but typically 17 in O. puertoricensis and O. talaje), and the
      length of the hypostome, which is clearly longer in O. rioplatensis than in O.
      talaje. Morphological details of the adults of these species are inadequate for
      taxonomic purposes. The genetic distance between O. puertoricensis and O.
      rioplatensis, based on 16S rDNA sequencing, is approximately 12.7%. Variability
      in some morphological features, using multivariate morphometric discrimination to
      assess congruence between populations, was examined among larval specimens of O.
      talaje and O. puertoricensis collected from the United States, and Central and
      South America. Larval specimens of O. talaje from Guatemala (near the type
      locality of the species) were morphologically different from Mexican and southern
      U.S. populations originally described as O. talaje. In the absence of DNA data
      for these populations, and because of inadequate statistical discrimination among
      body characters, we prefer to refer to the Mexican and U.S. material as O. nr.
      talaje until further analysis of population variability is conducted using an
      adequate sample size.

PMID- 18826025
TI  - Species composition and distribution of adult Anopheles (Diptera: Culicidae) in
      Panama.
AB  - Anopheles (Diptera: Culicidae) species composition and distribution were studied
      using human landing catch data over a 35-yr period in Panama. Mosquitoes were
      collected from 77 sites during 228 field trips carried out by members of the
      National Malaria Eradication Service. Fourteen Anopheles species were identified.
      The highest average human biting rates were recorded from Anopheles
      (Nyssorhynchus) albimanus (Wiedemann) (9.8 bites/person/night) and Anopheles
      (Anopheles) punctimacula (Dyar and Knab) (6.2 bites/person/night). These two
      species were also the most common, present in 99.1 and 74.9%, respectively, of
      the sites. Anopheles (Nyssorhynchus) aquasalis (Curry) was encountered mostly in
      the indigenous Kuna Yala Comarca along the eastern Atlantic coast, where malaria
      case history and average human biting rate (9.3 bites/person/night) suggest a
      local role in malaria transmission. An. albimanus, An. punctimacula, and
      Anopheles (Anopheles) vestitipennis (Dyar and Knab) were more abundant during the
      rainy season (May-December), whereas An. aquasalis was more abundant in the dry
      season (January-April). Other vector species collected in this study were
      Anopheles (Kerteszia) neivai (Howard, Dyar, and Knab) and Anopheles (Anopheles)
      pseudopunctipennis s.l. (Theobald). High diversity of Anopheles species and six
      confirmed malaria vectors in endemic areas of Panama emphasize the need for more
      detailed studies to better understand malaria transmission dynamics.

PMID- 18826026
TI  - Potential distribution of two species in the medically important Anopheles
      minimus complex (Diptera: Culicidae).
AB  - Anopheles minimus Theobald (=An. minimus A) and possibly Anopheles harrisoni
      Harbach & Manguin (=An. minimus C) are important malaria vector species in the
      Minimus Complex in Southeast Asia. The distributions of these species are poorly
      known, although detailed information could benefit malaria vector incrimination
      and control. We used published collection records of these species and
      environmental geospatial data to construct consensus ecological niche models
      (ENM) of each species' potential geographic distribution. The status of the
      Indian taxon An. fluviatilis S as a species distinct from An. harrisoni has been
      debated in the literature, so we tested for differentiation in ecological niche
      characteristics. The predicted potential distribution of An. minimus is more
      southerly than that of An. harrisoni: Southeast Asia is predicted to be more
      suitable for An. minimus, and China and India are predicted more suitable for An.
      harrisoni, so An. harrisoni seems to dominate under cooler conditions. The
      distribution of An. minimus is more continuous than that of An. harrisoni:
      disjunction in the potential distribution of the latter is suggested between
      India and Southeast Asia Anopheles fluviatilis S occurrences are predicted within
      the An. harrisoni ecological potential, so we do not document ecological
      differentiation that might reject conspecificity. Overall, model predictions
      offer a synthetic view of the distribution of this species complex across the
      landscapes of southern and eastern Asia.

PMID- 18826027
TI  - Sexual differences in larval molting rates in a protandrous mosquito (Diptera:
      Culicidae) species, Aedes sierrensis.
AB  - Day-old larval Aedes sierrensis collected from six newly flooded treeholes in
      northern California were reared individually in the laboratory under simulated
      field conditions to compare larval developmental rates of males and females. Time
      to adult eclosion ranged from 133 to 219 d for this generally univoltine, winter
      developing species. Males experienced significantly shorter first, second, and
      third larval instars than females. Females spent significantly less time as
      fourth instars (whose endpoint is determined by photoperiod). Length of pupal
      stage was equal for males and females. Time to mean adult eclosion differed among
      treeholes but was not determined by latitudinal position of treehole. Wing
      lengths were shorter for males than females in this sexually dimorphic species
      and also differed significantly among treeholes. Wing lengths were significantly
      correlated with total developmental time, but females spending more time in the
      fourth instar did not emerge as larger adults. In natural treeholes, resource
      utilization during rapid development by Ae. sierrensis males may limit the size
      and number of females produced from the same cohort if resources are limiting.

PMID- 18826028
TI  - Exotic grass invasion reduces survival of Amblyomma americanum and Dermacentor
      variabilis ticks (Acari: Ixodidae).
AB  - Exotic plants often invade areas of high human activity, such as along trails,
      roads, and forest edges, and in disturbed riparian areas. These same habitat
      types are also favored by ticks. This convergence suggests that habitat
      modifications caused by exotic plant invasions may mediate disease vector habitat
      quality, indirectly affecting human disease risk at the local spatial scale. We
      tested the hypothesis that experimental invasions of Japanese stiltgrass,
      Microstegium vimineum (Trin.) A. Camus, alter soil surface microclimate
      conditions, thereby reducing habitat quality for ticks. Microstegium is an exotic
      annual grass that is highly invasive throughout the eastern United States where
      the vector ticks Amblyomma americanum (Linnaeus) and Dermancentor variabilis
      (Say) occur. Ticks (n=100 per species) were introduced into experimentally
      invaded and native vegetation control plots (n=5 per treatment). D. variabilis
      mortality rate increased 173% and A. americanum mortality rate increased 70% in
      the invaded plots relative to those in control plots. Microstegium invasion also
      resulted in a 13.8% increase in temperature and an 18.8% decrease in humidity,
      which are known to increase tick mortality. We predict that areas invaded by
      Microstegium will have lower densities of host-seeking ticks and therefore
      reduced human disease risk. Our results emphasize the role of invasive species in
      mediating disease vector populations, the unpredictable consequences of
      biological invasions, and the need for integrative management strategies that can
      simultaneous address exotic plant invasions and vector-borne disease.

PMID- 18826029
TI  - Feeding patterns of Haemagogus capricornii and Haemagogus leucocelaenus (Diptera:
      Culicidae) in two Brazilian states (Rio de Janeiro and Goias).
AB  - We present the identification of bloodfeeding sources of Haemagogus (Haemagogus)
      capricornii Lutz and Haemagogus (Conopostegus) leucocelaenus (Dyar & Shannon)
      (Diptera: Culicidae) from different regions of Brazil, as analyzed by precipitin
      tests. Anti-sera for bird, bovine, equine, human, opossum, and rodent were used.
      Two hundred one mosquitoes were examined (147 Hg. leucocelaenus and 54 Hg.
      capricornii), of which 177 reacted for some anti-serum. For Hg. leucocelaenus, 86
      (68.3%) reacted to one blood source, 38 (30.2%) to two sources, and two (1.6%) to
      three sources; the combinations of bird + human (18.4%), bird + rodent (15.8%),
      and bird + marsupial (15.8%) were the most frequent. For Hg. capricornii, 34
      (66.7%) reacted to one blood source; combinations bird + rodent (37.5%) and bird
      + marsupial (25%) were the most frequent combinations. Mosquito preference for
      bloodfeeding sources was different in these areas, possibly because of the
      availability of sources. This diversity of sources can have important
      epidemiological implications.

PMID- 18826030
TI  - CNAct-1 gene is differentially expressed in the subtropical mosquito Culex
      nigripalpus (Diptera: Culicidae), the primary West Nile Virus vector in Florida.
AB  - Analysis of differentially expressed genes is a common molecular biological tool
      to investigate changes in mosquito genes after a bloodmeal or parasite exposure.
      We report here the characterization of a differentially expressed actin gene,
      CNAct-1, from the subtropical mosquito, Culex nigripalpus Theobald (Diptera:
      Culicidae). The CNAct-1 genomic clone is 1.525 kb, includes one 66-bp intron, and
      a 328-bp 3'-untranslated region. The 376-amino acid putative translation product
      shares high similarity with muscle-specific actin proteins from other insects,
      including Culex pipiens pipiens L., Aedes aegypti (L.), Anopheles gambiae Giles
      and Drosophila melanogaster (Meigen). CNAct-1 is expressed in second and third
      instars, late pupae, and adult females and males. Interestingly, Cx. nigripalpus
      actin was highly expressed in female mosquito midgut tissue isolated 6-12 h after
      ingestion of a bloodmeal. This expression profile indicates a unique function for
      CNAct-1 in midgut processes that are initiated after blood ingestion.

PMID- 18826031
TI  - Operational impact of DDT reintroduction for malaria control on Anopheles
      arabiensis in Mozambique.
AB  - ABSTRACT With the increase in indoor residual spraying in many internationally
      and nationally funded malaria control programs, and affirmation by World Health
      Organization (WHO) that DDT is appropriate for use in the absence of longer
      lasting insecticide formulations in some malaria endemic settings, DDT has been
      reintroduced as a major malaria control intervention in Africa. Indoor residual
      spraying with DDT was reintroduced into Mozambique for malaria control in 2005,
      and it is increasingly becoming the main insecticide used for malaria vector
      control in Mozambique. The selection of DDT in Mozambique is evidence-based,
      taking account of the susceptibility of Anopheles arabiensis (Patton) and
      Anopheles gambiae (Giles) s.s. to all the available insecticide choices, as well
      as relative costs of the insecticide and the logistical costs of spraying. Before
      this time in Mozambique, DDT was replaced by h-cyhalothrin in 1993. Resistance
      occurred quickly to this insecticide, and in 2000 the pyrethroid was phased out
      and the carbamate bendiocarb was introduced. Low-level resistance was detected by
      biochemical assay to bendiocarb in 1999 in both Anopheles funestus (Giles) and
      An. arabiensis, although this was not evident in WHO bioassays of the same
      population. In the 2000-2006 surveys the levels of bendiocarb resistance had been
      selected to a higher level in An. arabiensis, with resistance detectable by both
      biochemical and WHO bioassay. The insecticide resistance monitoring program
      includes assessment of field populations by standard WHO insecticide
      susceptibility assays and biochemical assays. Monitoring was established in 1999,
      and it was maintained as part of an operational monitoring and evaluation program
      thereafter.

PMID- 18826032
TI  - Novel arthropod repellent, BioUD, is an efficacious alternative to deet.
AB  - For >50 yr, N,N-diethyl-3-methylbenzamide (deet) has been the standard for
      arthropod repellents and has been an important tool to protect people from
      disease agents carried by ticks, mosquitoes, and other arthropods. However, some
      people avoid using deet because of concerns about adverse health effects. In
      2007, a new repellent, BioUD, with the active ingredient 7.75% 2-undecanone,
      originally derived from wild tomato (Lycopersicon hirsutum Dunal f. glabratum C.
      H. Mull) plants, was registered by the U.S. Environmental Protection Agency. In
      the current study, repellent efficacy of BioUD was compared using arm-in-cage
      studies with 7 and 15% deet against the mosquitoes Aedes aegypti (L.) and Aedes
      albopictus Skuse. No differences were found in mean repellency over 6 h after
      application between BioUD versus 7 and 15% deet for Ae albopictus. For Ae.
      aegypti, no differences were found over the same time period for 7% deet.
      Compared with 15% deet, BioUD mean repellency was lower over the 6-h test period.
      Human subject field trials were conducted in North Carolina, United States, and
      Ontario, Canada, comparing the repellency of BioUD to products containing 25 and
      30% deet. BioUD provided the same repellency or was more efficacious than 25 and
      30% deet, respectively, in these studies. Laboratory trials were conducted to
      determine the repellent activity of BioUD against the American dog tick,
      Dermacentor variabilis (Say), on human skin and cloth. BioUD repelled ticks at
      least 2.5 h after application to human skin. On cloth, no differences in mean
      repellency were found through 8 d after application between BioUD and 7% deet. In
      a two-choice test for BioUD versus 15% deet on filter paper, ticks spent
      significantly more time on the deet-treated surface than the BioUD-treated
      surface. Based on these studies in toto, BioUD is an efficacious alternative to
      deet in its repellent activity.

PMID- 18826033
TI  - Ability of 4-poster passive topical treatment devices for deer to sustain low
      population levels of Ixodes scapularis (Acari: Ixodidae) after integrated tick
      management in a residential landscape.
AB  - In a recent study, the combined use of 4-Posters and Maxforce TMS bait boxes
      along with a barrier application of deltamethrin resulted in accelerated control
      of Ixodes scapularis Say by sequentially attacking each postembryonic life stage.
      We report the results of a follow-up study to test the ability of 4-Posters used
      alone to sustain the high levels of control achieved through the integrated tick
      management (ITM) approach after withdrawal of the bait boxes. In the first year
      after withdrawal, we observed declines in the level of control of larvae on small
      mammals, as well as of numbers of host-seeking larvae in the treatment area.
      There was no difference in the level of control of host-seeking adults in the
      treatment area after 2 yr. Within 2 yr, we observed a decline in control of
      subadult ticks infesting small mammals, but continued to see significant control
      of both host-seeking nymphs (85.9%) and larvae (89.0%) in the treatment area. The
      inconsistency that we observed between the apparent ability of 4-Posters to
      sustain high levels of control of host-seeking ticks, although having less effect
      on tick burdens on small mammal hosts, may be explained by the host-seeking
      ecology of immature I. scapularis.

PMID- 18826034
TI  - Differential response to diazinon and coumaphos in a strain of Boophilus
      microplus (Acari: Ixodidae) collected in Mexico.
AB  - Boophilus microplus, collected from Nuevo Leon, Mexico, were found to be highly
      resistant to diazinon but not highly resistant to coumaphos, suggesting that
      different mechanisms of resistance were present in these ticks than other Mexican
      organophosphate (OP)-resistant ticks reported previously. When exposed to
      coumaphos and piperonyl butoxide or triphenylphosphate, the LCso estimate was
      reduced by 3.5- and 6.3-fold, respectively, suggesting that mono-oxygenases
      and/or esterases were involved in resistance to coumaphos. Additionally, it was
      determined that this strain had an Acetylycholinesterase (AChe) that was
      insensitive to the active form of coumaphos, coroxon, taking at least 24 min
      longer to reach 50% reduction in AChE activity compared with the susceptible
      strain. When exposed to diazinon, none of the synergists tested significantly
      lowered the LC50. However, it was determined that it took six times longer to
      reach 60% inhibition of AChE in the resistant strain compared with the
      susceptible strain when exposed to the active form of diazinon, diazoxon.
      Insensitive AChE seems to be very common in OP-resistant B. microplus. The
      potential benefits for the development of a field-portable AChE inhibition assay
      kit are discussed.

PMID- 18826035
TI  - Determination of permethrin resistance allele frequency of human head louse
      populations by quantitative sequencing.
AB  - A quantitative sequencing (QS) protocol that detects the frequencies of sodium
      channel mutations (M815I, T917I, and L920F) responsible for knockdown resistance
      in permethrin-resistant head lice (Pediculus humanus capitis De Geer) was tested
      as a population genotyping method for use as a preliminary resistance monitoring
      tool. Genomic DNA fragments of the sodium channel a-subunit gene that encompass
      the three mutation sites were polymerase chain reaction (PCR)-1 amplified from
      individual head lice with either resistant or susceptible genotypes, and combined
      in various ratios to generate standard DNA template mixtures for QS. After
      sequencing, the signal ratios between resistant and susceptible nucleotides were
      calculated and plotted against the corresponding resistance allele frequencies.
      Quadratic regression coefficients of the plots were close to 1, demonstrating
      that the signal ratios are highly correlated with the resistance allele
      frequencies. Resistance allele frequencies predicted by QS, using either "pooled
      DNA" (DNA extracted from individual louse specimens and pooled) or "pooled
      specimen DNA" (DNA simultaneously extracted from multiple louse specimens),
      agreed well with those determined by individual sequencing, confirming the
      reliability and accuracy of QS as a population genotyping method and validating
      our approach of using the pooled specimen DNA as the DNA template for QS. Our
      protocol for QS was determined to be highly reliable for the prediction of
      resistance allele frequencies higher than approximately 7.4% at the 95%
      confidence level. According to the resistance allele frequencies determined by
      QS, pyrethroid resistance varies substantially among different geographical
      regions, emphasizing the importance of early resistance detection and proper
      management strategies.

PMID- 18826036
TI  - Blood-feeding behavior of vesicular stomatitis virus infected Culicoides
      sonorensis (Diptera: Ceratopogonidae).
AB  - To determine whether vesicular stomatitis virus (VSV) infection of Culicoides
      sonorensis Wirth & Jones (Diptera: Ceratopogonidae) affects subsequent blood
      feeding behavior, midges injected with either virus-infected or virus-free cell
      lysates were allowed to blood feed for short (10-min) or long (60-min) periods on
      2, 3, and 4 d postinoculation (DPI). Generalized linear mixed models were fit to
      test the effects of infection status, duration of feeding period, and DPI on the
      percentage of females that blood fed. VSV-infection significantly reduced the
      percentage of females that blood fed on 2 DPI, the day of peak virus titer. On 3
      DPI a significantly greater percentage of midges blood fed when allowed 60 min to
      feed. This effect was not seen on 2 and 4 DPI and was not dependent on VSV
      infection status. The impact of changes in blood-feeding behavior by infected
      insects on virus transmission is discussed.

PMID- 18826037
TI  - Host feeding pattern of Japanese encephalitis virus vector mosquitoes (Diptera:
      Culicidae) from Kuttanadu, Kerala, India.
AB  - Identification of blood meals of vector mosquitoes is an important tool in the
      epidemiological investigations of vector-borne diseases. The blood meals of three
      mosquito species involved in the transmission of Japanese encephalitis virus
      (JEV) from the Kuttanadu area, Kerala, were determined using the agarose gel
      diffusion technique. A total of 4959 blood smears belonging to Culex (Culex)
      tritaeniorhynchus Giles (3273), Cx. (Culex) gelidus Theobald (64), Mansonia
      (Mnd.) indiana Edwards (735) ,and Ma. (Mnd.) uniformis (Theobald) (887) were
      tested. Cx. tritaeniorhynchus had predominantly fed on bovids (46.4%), and a good
      proportion (29%) had fed on more than one host. Cx. tritaeniorhynchus was highly
      zoophagic, and human feeding accounted for only 1.5% of those individuals
      successfully tested. Cx. gelidus showed bovid feeding at 36% and pig feeding at
      12.5%. The test results showed 42.3% Ma. indiana and 12.2% Ma. uniformis had fed
      on humans. Multiple feeding was observed in Ma. indiana and Ma. uniformis, and
      most of the double feedings were from bovids and ovids (7.9 and 20.1%,
      respectively). Pig feeding accounted for 4.8% of the feedings by Cx.
      tritaeniorhynchus, 5.3% of Ma. indiana, and 6.4% of Ma. uniformis. This study is
      significant because of the role played by these mosquitoes in the transmission of
      JEV in the Kuttanadu area of Kerala, India.

PMID- 18826038
TI  - Source of host blood affects prevalence of infection and bacterial loads of
      Yersinia pestis in fleas.
AB  - Yersinia pestis, the etiological agent of plague, is transmitted by multiple flea
      species. Previous studies have reported wide variability in transmission
      efficiency among competent vectors. However, it is unclear to what extent such
      variation is explained by methodological differences among studies. To optimize
      an artificial feeding system where fleas are infected with controlled numbers of
      Y. pestis under standardized laboratory conditions that could be used to
      systematically compare vector efficiency, we sought to test the effect of host
      bloodmeal source on (1) the flea's ability to remain infected with Y. pestis and
      (2) bacterial loads in fleas. Here, we demonstrate that both prevalence of
      infection with a virulent strain of Y. pestis (CO96-3188) and bacterial loads in
      rock squirrel fleas (Oropsylla montana) are affected by host-associated blood
      factors. The generality of this observation was confirmed by repeating the study
      using the rat flea (Xenopsylla cheopis) and a commonly used avirulent laboratory
      strain of Y. pestis (A1122). Implications of the results for rate of spread of Y.
      pestis in naturally infected host populations are discussed.

PMID- 18826039
TI  - Mosquito vectors of West Nile Fever in Israel.
AB  - West Nile fever (WNF) is endemic in Israel. In 1999, country-wide adult mosquito
      surveys were initiated and intensified after the 2000 country-wide outbreak of
      WNF in humans. In 8 consecutive yr, groups of male and female specimens of
      different species and from different locations were tested for infection with
      West Nile virus (WNV). Three species made up >87% of the total catch: Culex
      pipiens L. (52%), with an infection rate (IR) of 0.5; Cx. perexiguus Theobald
      (20%), with an IR of 2.7; and Aedes caspius Pallas (15%), with an IR of 0.6. The
      geographical and temporal distribution of WNV-infected mosquitoes was similar but
      was not parallel to the seasonal abundance of the populations. The seasonal
      occurrence of human cases is in correlation with the finding of WNV-positive
      mosquito specimens reaching a peak 1 mo later than the mosquito peak. The
      relative importance of the mosquito species in the epidemiology of WNF is
      discussed. Cx. perexiguus is considered the major vector of WNF in Israel.

PMID- 18826040
TI  - Prevalence of spotted fever group rickettsiae in Ixodes ricinus (Acari: Ixodidae)
      in southern Germany.
AB  - Host-seeking Ixodes ricinus (L.) (Acari: Ixodidae) ticks were collected
      systematically, from May to September 2006, at selected sites in southern
      Germany, including a large city park in Munich. Polymerase chain reactions for
      amplification of genes of the rickettsial citrate synthase (gltA), the outer
      membrane proteins A and B (ompA and ompB), and the 16S rDNA were used to
      investigate 2,861 specimens (adults and nymphs). GltA sequences of spotted fever
      group rickettsiae were detected in 151 of all samples (5.3%; 95% CI = 4.3-6.2%).
      Sequencing revealed Rickettsia helvetica in 91.4% of the samples and R.
      monacensis in 8.6%. Amplification of ompA was not possible for R. helvetica, but
      in all except one of the R. monacensis. The results were analyzed statistically
      to test the effects of season, location, developmental stage, and gender of the
      tick on prevalence of Rickettsia spp. Although rickettsial DNA was detected in
      all investigated sites, sites in natural forest areas had significantly higher
      prevalences than sites in landscaped city parks. Adult female and male ticks had
      a similar prevalence and were significantly more often infected than nymphs.
      Monthly differences were not statistically significant. These results clearly
      show that R. helvetica is widespread throughout the study region and could result
      in a threat to public health in areas of high prevalence.

PMID- 18826041
TI  - Who knows the bed bug? Knowledge of adult bed bug appearance increases with
      people's age in three counties of Great Britain.
AB  - The current reemergence of bed bugs in the western world has a multitude of
      causes. One of them may be low early detection rate of emerging infestations
      because of a current poor knowledge among the population of what bed bugs look
      like. In a survey conducted in three counties of the United Kingdom, 10% of 358
      individuals recognized the bed bug when presented with a live adult. Older people
      were more likely to correctly identify the bed bug. If an increasing knowledge of
      the bed bug appearance facilitates early detection of infestations, the
      hospitality and travel industry may benefit from educating their staff on the bed
      bug appearance.

PMID- 18826042
TI  - Additions to the known U.S. distribution of Latrodectus geometricus (Araneae:
      Theridiidae).
AB  - The range of the brown widow spider Latrodectus geometricus C. L. Koch includes
      much of Africa and South and Central America. This medically important spider has
      been recently introduced to Japan, Indonesia, Papua New Guinea, Australia,
      Hawaii, and California. After the identification of the brown widow spider in New
      Orleans, LA, and southern Mississippi, surveys in the southeastern United States
      were conducted from the fall of 2006 through February 2008. We found populations
      of brown widow spiders in Georgia, Texas, and multiple localities in southeastern
      Louisiana and Mississippi. In Mississippi, specimens were collected as far north
      as a county bordering Tennessee. In New Orleans, the brown widow spider has been
      commonly collected from various locations where human contact is likely.

PMID- 18826043
TI  - Affinity chromatography: methods and protocols. Preface.

PMID- 18826044
TI  - Affinity chromatography: history, perspectives, limitations and prospects.
AB  - Biomolecule separation and purification has until very recently steadfastly
      remained one of the more empirical aspects of modem biotechnology. Affinity
      chromatography, one of several types of adsorption chromatography, is
      particularly suited for the efficient isolation of biomolecules. This technique
      relies on the adsorbent bed material that has biological affinity for the
      substance to be isolated. This review is intended to place affinity
      chromatography in historical perspective and describe the current status,
      limitations and future prospects for the technique in modern biotechnology.

PMID- 18826045
TI  - Immobilized metal ion affinity chromatography of native proteins.
AB  - Immobilized metal affinity chromatography (IMAC) is a common place technique in
      modem protein purification. IMAC is distinct from most other affinity
      chromatography technologies in that it can operate on a native, unmodified
      protein without the need for a specialized affinity "tag" to facilitate binding.
      This can be particularly important where a protein of interest is to be separated
      from a complex mixture such as serum or an environmental isolate. Relying on the
      interaction of specific surface amino acids of the target protein and chelated
      metal ions, IMAC can provide powerful discrimination between small differences in
      protein sequence and structure. Additionally, IMAC supports have been
      demonstrated to function effectively as cation exchangers, allowing for two modes
      of purification with a single column. This chapter provides methodologies to
      perform IMAC in its most fundamental form, that of the interaction between
      histidine and immobilized metal ions, those that enable purification of proteins
      that lack surface histidines and the operation of IMAC supports in cation
      exchange mode.

PMID- 18826046
TI  - Affinity precipitation of proteins using metal chelates.
AB  - Metal affinity precipitation has been successfully developed as a simple
      purification process for the proteins that have affinity for the metal ions. The
      copolymers of vinylimidazole with N-isopropylacrylamide are easily synthesized by
      radical polymerization. When loaded with Cu(II) and Ni(II) ions, these copolymers
      are capable of selectively precipitating proteins with natural metal-binding
      groups or histidine-tagged recombinant proteins.

PMID- 18826047
TI  - Immunoaffinity chromatography.
AB  - Immunonaffinity chromatography is a powerful technique for rapid purification of
      proteins. In a single-step purification, it is possible to purify proteins for
      testing in model systems and for conducting enzyme kinetic studies. Because the
      immunoaffinity-purified proteins are typically > 90-95% pure, depending on the
      starting material, interference from remaining contaminants is rare. This method
      describes an immunoaffinity chromatography technique for purifying proteins from
      over-expression in mammalian cell culture. The immobilization of the monoclonal
      antibody or polyclonal antiserum is presented. Conditions for purifying up to
      milligram quantities of protein are given, including a representative
      chromatogram.

PMID- 18826048
TI  - Dye ligand chromatography.
AB  - Dye affinity chromatography is a purification technique offering unique
      selectivities and high purification factors. Dye ligands may act as substrate
      analogs, offering affinity interactions with their corresponding enzymes. This
      chapter describes a dye ligand chromatography technique for purifying proteins
      from overexpression, in mammalian cell culture. The method begins with batch
      binding in order to rapidly select binding and elution conditions. Subsequently,
      gradient elution is employed to maximize the selectivity of the final packed bed
      chromatography method. Conditions for purification of a protein from mammalian
      cell culture on Cibacron blue are given with an accompanying sample chromatogram.

PMID- 18826049
TI  - Purification of proteins using displacement chromatography.
AB  - Displacement chromatography has several advantages over the nonlinear elution
      technique, as well as the linear elution mode, such as the recovery of purified
      components at high concentrations, less tailing during elution, high throughput
      and high resolution. Displacer affinity and its utilization are the critical
      components of displacement chromatography. Particularly, the nonspecific
      interactions between the displacer and the stationary phase can be exploited to
      generate high affinity displacers. This chapter will discuss the design and
      execution of displacer selection and implementation in a separation specifically
      focusing on its utilization in ion exchange chromatography.

PMID- 18826050
TI  - Rationally designed ligands for use in affinity chromatography: an artificial
      protein L.
AB  - Synthetic affinity ligands can circumvent the drawbacks of natural immunoglobulin
      (Ig)-binding proteins by imparting resistance to chemical and biochemical
      degradation and to in situ sterilization, as well as ease and low cost of
      production. Protein L (PpL), isolated from Peptostreptococcus magnus strains,
      interacts with the Fab (antigen-binding fragment) portion of Igs, specifically
      with kappa light chains, and represents an almost universal ligand for the
      purification of antibodies. The concepts of rational design and solid-phase
      combinatorial chemistry were used for the discovery of a synthetic PpL mimic
      affinity ligand. The procedure presented in this chapter represents a general
      approach with the potential to be applied to different systems and target
      proteins.

PMID- 18826051
TI  - Phage display of peptides in ligand selection for use in affinity chromatography.
AB  - Large repertoires of peptides displayed on bacteriophage have been extensively
      used to select for ligand-binding molecules. This is a relatively straightforward
      process involving several cycles of selection against target molecules, and the
      resulting ligands can be tailored to various applications. In this chapter we
      describe detailed methods to select peptide ligands for affinity chromatography,
      with particular focus on selection of peptides that mimic antigen epitopes. The
      selection process involves screening a phage peptide library against a monoclonal
      antibody, proving the peptide is an authentic epitope mimic and coupling the
      peptide mimotope to an affinity resin for purifying antibodies from human serum.
      There are several other applications of phage peptides that could be used for
      affinity chromatography; the approaches are outlined, but detailed methods have
      not been included.

PMID- 18826052
TI  - Preparation, analysis and use of an affinity adsorbent for the purification of
      GST fusion protein.
AB  - Methods are presented for the preparation, ligand density analysis and use of an
      affinity adsorbent for the purification of a glutathione S-transferase (GST)
      fusion protein in packed and expanded bed chromatographic processes. The protein
      is composed of GST fused to a zinc finger transcription factor (ZnF).
      Glutathione, the affinity ligand for GST purification, is covalently immobilized
      to a solid-phase adsorbent (Streamline). The GST-ZnF fusion protein displays a
      dissociation constant of 0.6 x 10(-6) M to glutathione immobilized to Streamline.
      Ligand density optimization, fusion protein elution conditions (pH and
      glutathione concentration) and ligand orientation are briefly discussed.

PMID- 18826053
TI  - Immobilized metal ion affinity chromatography of histidine-tagged fusion
      proteins.
AB  - Immobilized metal ion affinity chromatography (IMAC) is a ubiquitous technique in
      modem recombinant production and purification. The wide range of expression
      vectors for the production of histidine-tagged recombinant proteins as well as
      the variety of stationary supports for their separation make IMAC an attractive
      and versatile choice for fast and reliable protein purification. It is not
      uncommon for IMAC purification to yield near homogenous target protein, with
      purities over 95%. The small size of the histidine tag means that in many cases
      it can remain associated with the target protein without interference with its
      intended function, obviating the need for any potentially complicating tag
      removal steps. This chapter provides protocols for the routine purification of
      such histidine-tagged fusion proteins. As with any purification regime,
      complications with IMAC can arise. Lacking the absolute specificity of a
      biological ligand/ligate system such as the avidin/biotin interaction or an
      antibody and its cognate antigen, IMAC can sometimes display non-ideal product
      purity. The protocols described in this chapter provide strategies for the
      improvement in the purity of IMAC-purified proteins. Similarly, non-specific
      binding may reduce product yields and purity in some circumstances. Methodologies
      for enhancing the yield of the target protein are therefore provided.

PMID- 18826054
TI  - Methods for the purification of HQ-tagged proteins.
AB  - The HQ (H = histidine, Q = glutamine) tag is a small fusion tag that can be
      isolated using immobilized metal affinity columns. HQ-tagged proteins can be
      expressed and purified from bacterial cells under native and denaturing
      conditions, mammalian cells, insect cells, wheat germ and rabbit reticulocyte.
      Furthermore, HQ-tagged proteins can be purified using magnetic or non-magnetic
      resins in multiple formats from small to large-scale and manual or automated. In
      this chapter, we have described various protocols for the purification of HQ
      tagged proteins.

PMID- 18826055
TI  - Amylose affinity chromatography of maltose-binding protein: purification by both
      native and novel matrix-assisted dialysis refolding methods.
AB  - Maltose-binding protein (MBP) is a carrier protein for high level recombinant
      protein and peptide production from either the cytoplasm or periplasm of
      Escherichia coli. The affinity matrix for purifying MBP-passenger proteins
      utilizes amylose covalently attached to magnetic beads, agarose, or a chemically
      inert fast protein liquid chromatography (FPLC) matrix--exploiting the natural
      affinity of MBP for alpha-(1-->4)-maltodextrins in the stationary phase. A
      fundamental problem is the expression and purification failure of as much as 30%
      of all constructs, which is limiting for one of the best solubilizing carrier
      proteins available for recombinant expression. In this chapter, we have discussed
      aspects of MBP biology that can impact upon binding to the amylose affinity
      matrix including cloning considerations, structural complications, hydrophobic
      buffer additives and the presence of cellular biomolecules that bind or modify
      the matrix during purification. Chromatography conditions are presented for
      purification at very small scales of less than 0.5 mL using amylose magnetic
      beads, a batch and semi-batch method for small to moderate scale purifications up
      to approximately 35 mg and larger scale FPLC methods. A novel matrix-assisted
      dialysis refolding method is also described whereby MBP-passenger proteins can be
      refolded in the presence of amylose matrix in instances where native purification
      methods fail to bind the amylose matrix.

PMID- 18826056
TI  - Methods for detection of protein-protein and protein-DNA interactions using
      HaloTag.
AB  - HaloTag is a protein fusion tag which was genetically engineered to covalently
      bind a series of specific synthetic ligands. All ligands carry two groups, the
      reactive group and the functional/reporter group. The reactive group, the
      choloroalkane, is the same in all the ligands and is involved in binding to the
      HaloTag. The functional reporter group is variable and can carry many different
      moieties including fluorescent dyes, affinity handles like biotin or solid
      surfaces such as agarose beads. Thus, HaloTag can serve either as a labeling tag
      or as a protein immobilization tag depending on which ligand is bound to it.
      Here, we describe a procedure for immobilization of HaloTag fusion proteins and
      how immobilized proteins can be used to study protein-protein and protein-DNA
      interactions in vivo and in vitro.

PMID- 18826057
TI  - Site-specific cleavage of fusion proteins.
AB  - Where an affinity tag has served its purpose, it may become desirable to remove
      it from the protein of interest. This chapter describes the removal of such
      fusion partners from the intended protein product by cleavage with site-specific
      endoproteases. Methods to achieve proteolytic cleavage of the fusion proteins are
      provided, along with techniques for optimizing the yield of authentic product.

PMID- 18826058
TI  - The use of TAGZyme for the efficient removal of N-terminal His-tags.
AB  - The use of affinity tags and especially histidine tags (His-tags) has become
      widespread in molecular biology for the efficient purification of recombinant
      proteins. In some cases, the presence of the affinity tag in the recombinant
      protein is unwanted or may represent a disadvantage for the projected use of the
      protein, like in clinical, functional or structural studies. For N-terminal tags,
      the TAGZyme system represents an ideal approach for fast and accurate tag
      removal. TAGZyme is based on engineered aminopeptidases. Using human tumor
      necrosis factor alpha as a model protein, we describe here the steps involved in
      the removal of a His-tag using TAGZyme. The tag used (UZ-HT15) has been optimized
      for expression in Escherichia coli and for TAGZyme efficiency. The UZ-HT15 tag
      and the method can be applied to virtually any protein. A description of the
      cloning strategy for the design of the genetic construction, two alternative
      approaches and a simple test to assess the performance of the tag removal process
      are also included.

PMID- 18826059
TI  - Affinity processing of cell-containing feeds using monolithic macroporous
      hydrogels, cryogels.
AB  - Monolithic macroporous hydrogels, "cryogels," are produced by polymerization in a
      partially frozen state when the ice crystals perform as a porogen. Cryogels have
      a unique combination of properties: (i) large (10-100 microm) pores; (ii) minimal
      non-specific interactions due to the hydrophilic nature of the polymers; (iii)
      porosities exceeding 80-90%; (iv) good mechanical stability. These properties of
      cryogels allow for their application for direct capture of extracellularly
      expressed histidine-tagged protein from the fermentation broth and separation of
      different cell types.

PMID- 18826060
TI  - Monolithic bioreactors for macromolecules.
AB  - Enzymes immobilized on solid-phase matrices have found various applications in
      biotechnology, molecular biology and molecular diagnostics and can serve as
      industrial catalysts and as specific reagents for analytical procedures. A wide
      range of supports have been utilized for immobilization among which particle
      based supports are the most commonly implemented. Type of support used for
      immobilization is one of the key considerations in practical application due to
      different immobilization efficiency, ligand utilization and the mass transfer
      regime. The mass transfer between the mobile and the particulate stationary phase
      is often a bottleneck for the entire process due to slow pore diffusion of large
      molecules. In contrast, monoliths due to their structure enable almost flow
      independent properties. Consequently, the overall behavior of the immobilized
      ligand reflects its intrinsic reaction kinetics. Therefore, such an immobilized
      system is expected to allow higher throughput because of higher enzyme
      efficiency, especially pronounced for macromolecular substrates having low
      mobility. In this work, different methods for immobilization of enzymes on
      Convective Interaction Media monolithic supports are presented. In particular,
      enzymes acting on macromolecular substrates, such as trypsin, deoxyribonuclease
      and ribonuclease, are described in detail. Immobilized efficiency is evaluated
      for different immobilization procedures in terms of biologic activity and long
      term stability. Finally, their performance on real samples is demonstrated.

PMID- 18826061
TI  - Plasmid DNA purification via the use of a dual affinity protein.
AB  - Methods are presented for the production, affinity purification and analysis of
      plasmid DNA (pDNA). Batch fermentation is used for the production of the pDNA,
      and expanded bed chromatography, via the use of a dual affinity glutathione S
      transferase (GST) fusion protein, is used for the capture and purification of the
      pDNA. The protein is composed of GST, which displays affinity for glutathione
      immobilized to a solid-phase adsorbent, fused to a zinc finger transcription
      factor, which displays affinity for a target 9-base pair sequence contained
      within the target pDNA. A Picogreen fluorescence assay and/or an ethidium bromide
      agarose gel electrophoresis assay can be used to analyze the eluted pDNA.

PMID- 18826062
TI  - Affinity chromatography of phosphorylated proteins.
AB  - This chapter covers the use of immobilized metal ion affinity chromatography
      (IMAC) for enrichment of phosphorylated proteins. Some requirements for
      successful enrichment of these types of proteins are discussed. An experimental
      protocol and a set of application data are included to enable the scientist to
      obtain high-yield results in a very short time with pre-packed phospho-specific
      metal ion affinity resin (PMAC).

PMID- 18826063
TI  - Protein separation using immobilized phospholipid chromatography.
AB  - The chromatographic support containing monolayers of phospholipids offers novel
      modes in analyzing and separating proteins. The polar choline head groups on
      immobilized phosphatidylcholine were used for the affinity purification of
      phospholipase A (PLA). The purification process involves removing the
      contaminating proteins with detergent additives to the elution buffer such as
      short-chain alkylsulfonates. The lipid-bound PLA was eluted with acetonitrile or
      octyllysophosphatidylcholine. The purity of PLA was approximately 70% based on
      densitometric scans of gel electrophoresis. These results suggest that the lipid
      immobilized chromatography may be applied to develop purification methods for
      PLA, enzymes, and membrane proteins obtained from diverse cells.

PMID- 18826064
TI  - Analysis of proteins in solution using affinity capillary electrophoresis.
AB  - Analysis of protein interactions by means of capillary electrophoresis (CE) has
      unique challenges and rewards. The choice of analysis conditions, especially
      involving electrophoresis buffers, are crucial and not universal for protein
      analysis. If conditions for analysis can be worked out, it is possible to utilize
      CE quantitatively and qualitatively to characterize protein-ligand binding
      involving unmodified molecules in solution and taking place under physiological
      conditions. This chapter deals with the most important practical considerations
      in capillary electrophoretic affinity approaches, affinity CE (ACE). The text
      emphasizes the most critical factors for successful analyses and has application
      examples illustrating various types of information offered by ACE-based studies.
      Also included are step-by-step accounts of the two main classes of experimental
      design: the pre-equilibration ACE (in the form of CE-frontal analysis (CE-FA))
      and mobility shift ACE together with examples of their use. The ACE approaches
      for binding assays of proteins should be considered when the biological material
      is scarce, when any kind of labeling is not possible or desired, when the
      interacting molecules are the same size and when rapid and simple method
      development is a priority.

PMID- 18826065
TI  - Enhancing the efficacy and empowerment of older adults through group formation.
AB  - Research suggests that efficacy and empowerment are necessary for social
      engagement and that a sense of efficacy and empowerment exerts positive
      influences on older adults. However, little is known about how individual
      efficacy and empowerment are affected by group efficacy and empowerment in later
      life. To assess the impact of group involvement on the individual, the authors
      conducted a follow-up study with members of an art guild for older adults.
      Qualitative data were collected in 1997 and 2001 to ascertain the members'
      perceptions of group goals and accomplishments, membership benefits, the effect
      on the community, societal views about older adults, and the impact of group
      activities on the individual. The results clearly indicated that collective
      efficacy and empowerment through social engagement were beneficial to members as
      individuals and as a group, and contributed to well-being through a general sense
      of accomplishment and pride.

PMID- 18826066
TI  - A qualitative perspective of family resources among low income, African American
      grandmother-caregivers.
AB  - This ethnographic study describes a group of 7 low-income, African American,
      grandmother-caregivers' perceptions of family resources. An ethnographic design,
      enhanced by a genogram, captured those who were available and unavailable to
      provide support to the grandmother. The analysis used a constant comparative
      method to thematically capture grandmothers' perceptions of family support
      resources as absent, unavailable, dependent, and reliable support, and the
      circumstances that led to that status. The findings reveal that many African
      American grandmothers are rearing children with little family support, owing
      mainly to the devastation of negative social and economic conditions. The results
      suggest areas for improvement in social work assessment and intervention.

PMID- 18826067
TI  - Impact of support groups on well-being of older women.
AB  - The goal of this study was to determine whether differences in incidence of
      depression and level of well-being are manifested between older women, aged 60
      and older, who attend either (a) a peer-run support group, (b) a staff-run
      support group, or (c) a comparison group (i.e., who do not attend a support
      group). Thirty-six women participating in peer-run and staff-run support groups
      and 9 women receiving nongroup support were administered the Geriatric Depression
      Scale and the Philadelphia Geriatric Center Morale Scale. Separate analyses of
      variance were employed on each scale to determine the significance of differences
      in scores according to facilitator type (i.e., peer-run vs. staff-run vs.
      comparison group). Analysis of scores on the Geriatric Depression Scale indicated
      significant differences between women in the peer-run groups and women in the
      comparison group, but no significant differences between women in the peer-run
      groups and women in the staff-run groups or between women in the staff-run groups
      and women in the comparison group. Analysis of scores on the Philadelphia
      Geriatric Center Morale Scale did not indicate any significant differences
      between women based on facilitator type. Results of this study have implications
      for those who run face-to-face support groups for older adults, for those who
      train peer group facilitators, and for community agencies that desire to initiate
      a support group system for their clientele.

PMID- 18826068
TI  - Palliative healthcare: cost reduction and quality enhancement using end-of-life
      survey methodology.
AB  - American medical institutions throughout the 20th century prescribed high
      customer satisfaction, but when it came to death, largely ignored it. An
      accelerated accumulation of esoteric medical information and the application of
      this knowledge to affect new cures and longer lives instilled an unquestioning
      reverence for the medical community among the patient population. Diminishing
      marginal gains in life expectancy, escalating costs related to life sustaining
      technologies, and a psychographic shift in the dominant consumer base have
      challenged this traditional reverence. Armed with unprecedented access to medical
      information, a more knowledgeable and assertive patient population has emerged in
      the 21st century to institute its own standards of what constitutes quality
      health care. In terms of end of life care, this has meant recognition that the
      emotional needs of the dying have been largely underserved by the current
      American medical model. Patients and their families are no longer willing to
      accept the traditional medical perspective of death as failure and have numerous
      international palliative care models that serve as benchmarks of success when it
      comes to quality of dying. When cure is a possibility, Americans will pursue it
      at all costs, but when it is not a possibility, they want honest communication
      and the opportunity to say good-bye to their loved ones. In the context of these
      emergent needs, life review is offered as a solution. The value proposition
      targets not only dying patients and their families, but also society as a whole.

PMID- 18826069
TI  - Moving toward Medicare home health coverage for persons with Alzheimer's disease.
AB  - Medicare home health care policy does not incorporate research evidence of
      effective palliative home care interventions for Alzheimer's disease and dementia
      patients and caregivers. This article examines the dissonance between the needs
      and burdens of Alzheimer's disease patients and caregivers, research results on
      medical and palliative care interventions, and medicalized public policy in the
      Medicare home health benefit. The article asserts existing research establishes a
      prima facie case exists for the federal government to fund a Medicare Palliative
      Home Care for Alzheimer's disease demonstration project. The article cites the
      success of the Medicare Hospice Demonstration project and Hospice Medicare
      Benefit in reducing costs and improving client quality of life as precedent and a
      model for Alzheimer's disease. Other research implications are identified.

PMID- 18826070
TI  - An exploratory study of substance abuse among Latino older adults.
AB  - Substance abuse among older adults is on the rise. Of particular concern is the
      increase in alcohol and drug use predicted among Latino elders, expected to
      result from an upsurge in the Latino population and concurrent growth in the
      number of older adults. Providing effective treatment for this group will require
      age-specific, culturally competent interventions. However, few studies have
      focused on geriatric substance abuse among Latinos. This study aims to lay the
      groundwork for further research by examining perceptions of the problem among
      treatment providers and researchers in aging and substance abuse. Implications
      for social work research and practice are addressed.

PMID- 18826071
TI  - Rethinking needs assessment in planning services for older adults.
AB  - Needs assessments are widely used in the field of aging, and are considered
      valuable tools for planning service responses to unmet and undermet needs of
      older adults. This article describes a comprehensive needs assessment of
      Bermuda's older population and presents some of its findings to illustrate
      concerns about needs assessments that emerged from this experience. We suggest
      that even when needs assessments are carefully planned and adhere to generally
      recognized best practice principles, they may not be able to fully provide
      desired information. A revision of key assumptions about needs assessment is
      offered for researchers, planners, and community workers.

PMID- 18826072
TI  - An exploration of mental health literacy among African American clergy.
AB  - The purpose of this qualitative study was to explore African American clergy's
      mental health literacy with older congregants 60 years of age and older. Using a
      grounded theory approach, we recruited a purposive sample of 9 African American
      clergy representing diverse ages, denominations, locales, and educational levels.
      Data was coded and classified according to Kevin's (1976) typology of pastoral
      counseling and Jorm et al.'s (1997) conceptual model of mental health literacy.
      Findings from data analysis revealed study respondents were adherents of Kevin's
      Religious-Community (R-C) model. Additionally, the following themes emerged: loss
      of cognitive functioning, psychosocial stressors, religiosity, and appreciation
      for professional assistance, cultural barriers, and key informants/familiarity
      with formal mental health providers which partially maps onto Jorm et al.'s
      conceptual model of mental health literacy.

PMID- 18826073
TI  - Eldercare and employed caregivers: a public/private responsibility?
AB  - The National Alliance for Caregiving (NAC) and the American Association of
      Retired Persons (AARP, 2004) have reported that 21% of the U.S. population
      provides family caregiving services to someone over 18 years old. Seventy-nine
      percent (79%) of these caregivers provide care for someone aged 50 or older. The
      majority of caregivers work full or part-time, and nearly two-thirds of employed
      caregivers make work-related adjustments in order to provide care (NAC & AARP,
      2004). This article examines eldercare issues of employed caregivers, identifies
      current public and private policies addressing caregiver needs, presents a
      process model to assist organizations in creating family-friendly workplaces, and
      suggests social work roles that support family caregiving.

PMID- 18826075
TI  - [Impact factor of a biomedical journal. Is it justified to look for it?].

PMID- 18826074
TI  - Addressing the vision challenges of residents at a retirement community:
      collaborative research with a community partner.
AB  - Staff members at a community retirement village were concerned about the demise
      of a support group for residents with vision loss, and requested help developing
      effective services for residents with vision challenges. This study explored past
      barriers to support group participation, as they were perceived by residents,
      family members, and employees. The community partner worked collaboratively with
      the researcher in all phases of the study. Questionnaires were designed to elicit
      demographic data, diagnosed vision problems, level of adjustment to vision loss,
      well-being, and motivation for attending institutional programs about vision
      challenges. Residents responded to standardized vision and depression scales;
      qualitative questions were posed to all 3 groups concerning motivations for
      resident participation in program activities. Results indicated that, although
      many residents had diagnosed vision conditions, they were, in general, coping
      well with vision loss and did not report depressive symptoms. Participants
      considered ongoing personal contact and follow-up, a group design that offered
      the choice of educational presentations and/or process discussions, and
      individualized assistance with practical challenges to be critical to an
      effective program. This case study, utilizing a collaborative research process,
      generated requests for expanded social work services and an increased valuing of
      the social work role.

PMID- 18826076
TI  - [Complications on minimal access surgery for total hip arthroplasty].
AB  - INTRODUCTION: Recently, the surgical approach for total hip replacement has been
      refined and has been reduced in size. Controversies exist between advantages and
      complications it can present. OBJECTIVE: To show the complications of total hip
      arthroplasty by means of minimal access approach. METHODS: Thirty six patients,
      24 women and 12 men (mean age 48 years), grade IV hip arthrosis. Twenty four
      patients underwent cementless hip arthroplasty and 12 patients hybrid
      arthroplasty. The preoperative evaluation was done with Harris score. An initial
      lateral approach of 6 cm (100%) was performed. Complications were grouped on
      acetabular, femoral and soft tissue complications. RESULTS: Necrosis at the
      comissure of the wound was seen in 12 patients (33.33%), necrosis at the surface
      border of the wound in 10 patients (27.77%), mal positioning of the acetabular
      cup in 3 patients (8.33%), mal positioning of acetabular cup screws in 2 patients
      (5.55%), eccentric reaming of the acetabulum in one patient (2.77%), and femoral
      stem malalignment in one patients (2.77%). DISCUSSION: There are many reports on
      the advantages of minimal invasion total hip replacement but few on complications
      which include mal positioning of the acetabular cup, eccentric reaming of the
      acetabulum and femoral stem malalignment. Nevertheless, advantages include a
      decreased healing time and postoperative recovery with less pain and reduced
      blood loss. We recommend that this technique should remain in the hands of
      experienced orthopaedic surgeons.

PMID- 18826077
TI  - [Clinical results of hallux valgus minimally surgery].
AB  - INTRODUCTION: Hallux valgus is a frequent cause of pain, mainly in female
      population, characterized by deformity of the foot and important functional
      consequences. Open surgical techniques require relatively extensive incisions.
      Recently we see a tendency to use less invasive techniques with shorter
      hospitalization periods and better recovery. OBJECTIVE: To evaluate postsurgical
      clinical results in hallux valgus with minimally invasive surgery techniques
      according to the AOFAS scale. DESIGN: Longitudinal, prospective, descriptive and
      homodemic study. LOCATION: Hospital of Orthopedics and Traumatology, UMAE Puebla
      of the Mexican Institute of Social Security. MATERIAL AND METHODS: Twenty-nine
      patients with diagnosis of Hallux valgus treated between September 2004 and March
      2008 were included. According to the AOFAS scale, we collected data from before
      the surgery, at one month and at 6 months postoperatively. We used univariate
      analysis of frequencies, measures of central tendency for demographic variables
      and the Wilcoxon test to evaluate pre and postoperative results with support from
      the SPSS version 12 program. RESULTS: The global evaluation of minimally invasive
      surgical technique according to AOFAS showed an average in the preoperative
      period of 60.37 (95% CI, between 53.87-66.38), at one month of 89 (95% CI,
      between 85.18-90.81) and at 6 months of 96.62 (95% CI, between 94.63-98.70). Mean
      age was 42 years (20-65), 22 women (75.86%) and 7 men (24.13%). We observed
      differences in the preoperative period, at one month and at 6 months with a p <
      0.05 in global evaluation of AOFAS measurement scale for pain and function.
      DISCUSSION: Our results show that minimally invasive surgical technique is a good
      option for treatment of this pathology; they reveal the need to continue the
      study and to compare it with open surgical technique. Minimally invasive surgical
      technique, if properly done, reports good results and is an adequate therapeutic
      alternative for treatment of symptomatic hallux valgus.

PMID- 18826078
TI  - [Delay in skeletal maturity in Mexican patients with Legg-Calve-Perthes].
AB  - OBJECTIVE: To determine the degree of delayed skeletal maturity in patients with
      active Legg-Calve-Perthes disease (LCPD) with radiographic evaluation of bone age
      and the degree of fragmentation of the femoral head using the modified lateral
      pillar Herring classification. MATERIAL AND METHODS: Twenty patients with LCPD
      were studied with left hand and wrist anteroposterior simple X- rays to determine
      bone vs. chronologic age. They were also studied with anteroposterior pelvis
      simple X-rays to determine the modified lateral pillar Herring classification.
      RESULTS: Seventeen (17/20) patients with LCPD presented with chronologic mean age
      of 8.15-years-old in comparison to mean bone age of 6.62-years-old (delay in bone
      age of 22.89 months). We found a delay in bone age; mean of 28 months in children
      6 to 10-years-old, mean of 8 months in children 10 years and older by quadratic
      regression. DISCUSSION: Previous series report patients with LCPD delayed bone
      age of 22 months. Our report present a series with delayed in bone age of a mean
      of 28 months, in children with LCPD of 6- 10-years-old. CONCLUSIONS: The degree
      of delayed bone age in LCPD, in our Mexican population is of 28 months in
      children 6- 10-years-old, and only 8 months in children ten-years-old.

PMID- 18826079
TI  - [Use of expanders in surgical treatment of kyphosis in patients with
      myelomeningocele].
AB  - INTRODUCTION: Numerous surgical techniques of instrumentation have been described
      in surgical management of kyphosis in children with myelomeningocele. However,
      complications related to surgical technique or the soft tissue reconstruction can
      exist. Tissue expansion is a technique that can be used before spine surgery with
      damaged skin. MATERIAL AND METHODS: We studied 11 patients with myelomeningocele
      and kyphosis. All had dural sac closure in neonatal stage as well as thoracic or
      upper lumbar lesion with severe neurologic deficit. Patients were evaluated by a
      plastic surgeon that placed a soft tissue expander, as the first stage of
      reconstruction. Kyphectomy, instrumentation, posterior fusion, expander removal
      and wound closure were done as a second stage. RESULTS: Fifteen tissue expanders
      were placed in 11 patients; 4 patients had 2 expanders and 7 patients had one.
      All the expanders were placed in the back, 9 expanders were placed in thoracic
      region and 6 in the lumbar region with an average of 17 weeks in the body. No
      complications were detected in the postoperative period of the tissue expansion.
      Neurologic deficit was thoracic in 9 patients and upper lumbar in 2 patients; we
      used for instrumentation ACM plates in 6 patients, SSI with Luque rods in 2
      patients, crossed nails in 1 patient, 3.5 DCP in one patient, and we did not use
      instrumentation in one patient. Four patients (36.3%) had complications related
      to the kyphectomy and instrumentation in the postoperative period. CONCLUSIONS:
      Use of tissue expanders before the surgical management of kyphosis in
      myelomeningocele is a good option to avoid complications of soft tissue coverage,
      evaluation of patients and indications for expanders must be done by a plastic
      surgeon.

PMID- 18826080
TI  - [Radiological evaluation of the flexibles pes planus treated with conic
      endorthesis].
AB  - OBJECTIVE: To determine the correction of flexible pes planus by means of the
      placement of a conic endorthesis in the subtalar joint. Outcomes were based on
      measures of the Moreau-Costa-Bartani and talar-navicular angles. MATERIAL AND
      METHODS: A series of 22 patients of both genders (7 to 13 years-old), were
      operated on both feet. The subtalar joint was stabilized by placement of a conic
      endorthesis. All of them were diagnosed as flexible pes planus, and 44 feet were
      operated on. All cases had previous conservative treatment without improvement.
      In these patients the Moreau-Costa-Bartani and talar-navicular angles were
      measured on lateral and dorsoplantar projections respectively, and compared pre
      and post-operatively. RESULTS: Significant correction of the analyzed angles was
      achieved. We obtained less than 130 p in the "A" angle and less than 150 p in the
      "B" in the lateral projection, and less than 80 p in the dorsoplantar projection.
      CONCLUSION: Normal Moreau-Costa-Bartani and talarnavicular angles were achieved
      by means of the subtalar placement of a conic endortheses, and normal ranges were
      obtained in the simple X-rays measures.

PMID- 18826081
TI  - [Epidemiology of traumatic lesions in children seen at Cerralvo General
      Hospital].
AB  - OBJECTIVE: To show traumatic injures in children under sixteen-years-old, managed
      from April 2004 to March 2005, in Cerralvo General Hospital, Nuevo Leon, Mexico.
      MATERIALS AND METHODS: Cross-Sectional Study. We filled out special formats in
      every pediatric patient seen in our hospital for traumatic lesion. RESULTS: We
      attended 535 children (65.0% were male and 34.9% female). Most of the patients
      (81.3%) had no health insurance. We checked 49.8% on Saturday, Sunday and Monday.
      Most of the accidents were at home (55.7%), and 44.4% were in the evening.
      Wounds, contusions and fractures accounted for 79.2% of the lesions. The head was
      affected with 37.8%, the upper extremity in 29.9% and the lower extremity in
      22.4%. The injures were caused by falls in 46.7%, followed by blunt objects in
      11.9% and motor vehicles in 11.7%. CONCLUSION: We conclude that injures in small
      cities as in northeast Nuevo Leon, are less serious than injures in big cities.

PMID- 18826082
TI  - [Clinical arthroscopic correlation of knee lesions in pediatric patients].
AB  - INTRODUCTION: Intraarticular injuries of pediatric patients have a different
      approach to that of adult patients. Part of this problem lies in minimizing
      children's symptoms by parents as well as physicians thinking they are less prone
      to injuries that require surgical management. Arthroscopy has helped in
      diagnosing these injuries, but the use of this method could be over used. We
      present a correlation of clinical diagnosis and arthroscopic findings. MATERIAL
      AND METHODS: We conducted a transversal retrolective study in "Hospital Central
      Sur Petroleos Mexicanos". We compared clinical diagnoses vs. arthroscopic
      findings in a group of patients younger than 18 years operated on from June 1995
      to February 2005. RESULTS: One hundred and thirty one patients were operated on,
      and subdivided in two groups: younger that 13 years and older that 13 years, 42%
      preoperative and postoperative diagnoses correlated in the first group, and 46%
      for the second group. CONCLUSION: Arthroscopic surgery is useful in achieving
      better diagnostic precision, as well as it gives us the opportunity to
      specifically treat knee injuries in pediatric patients.

PMID- 18826083
TI  - [Treatment of claw toes deformity].
AB  - INTRODUCTION: Within pathologic alterations that affect foot and ankle, claw toes
      deformity is one of the most frequent with an incidence of 20%. There are many
      surgical options to treat this deformity reported in literature. OBJECTIVE: To
      show clinical experience of the Orthopedic Department of Hospital "Victorio de la
      Fuente Narvaez" in lesser toes claw deformity treated with resection of the
      proximal interphalangic joint, as a treatment for alignment and better function.
      MATERIAL AND METHODS: We performed a retrospective clinical trial, in the period
      between January 2001 and December 2003 with a mean follow up of 14 months. Twenty
      three patients were included (43 fingers) 17 female and 6 male (mean age 54)
      bilateral deformity in 7 patients (19 fingers) unilateral in 16 patients (24
      fingers); the most commonly affected finger was the second (55.8%). Clinical and
      radiographic diagnosis were made. Surgical treatment indication was determined in
      relation to functional impairment, type of shoe used and concomitant pathology.
      Functional assessment was done with AOFAS scale and a visual analogue scale.
      RESULTS: Satisfactory results were reported in 18 patients (78.3%), not entirely
      satisfactory results 3 patients (13%) and not satisfactory results in 2 patients
      (8.7%). CONCLUSION: Accordingly with the results obtained we can conclude that
      the surgical technique is simple and effective in treatment of lesser toes claw
      deformity, returning function and morphology of the forefoot.

PMID- 18826084
TI  - [Evaluation of healthy Mexican adolescents. Based on the guidelines provided by
      the Pediatric Orthopedic Society of North America].
AB  - INTRODUCTION: Numerous questionnaires have been developed to assess function in
      activities of daily living. One of these was developed by the Pediatric
      Orthopedic Society of North America (POSNA) and is known as the PODCI (Pediatric
      Outcomes Data Collection Instrument). This instrument has been translated to
      Spanish but had not been validated in a normal Mexican population. OBJECTIVE: To
      validate the translated version of the PODCI when applied to a population of
      Mexican adolescents without any orthopedic condition and obtain reference scores
      to be considered normal. METHODS: The questionnaire was applied to 87 adolescents
      and their parents; range, mean, 95% confidence intervals and standard deviation
      were determined for each scale. RESULTS: High scores were observed for all
      scales, the lowest mean was 87.2 and the highest was 99.9. No significant
      difference was noted between the questionnaires answered by the adolescents or
      their parents. CONCLUSIONS: The translated version of the PODCI was validated in
      this population. We determined that the maximum score of 100 is obtainable and we
      can infer that an adolescent who scores below 80 is functioning at a level that
      is lower than normal.

PMID- 18826085
TI  - [Amputation as a treatment for complications on a traumatic dislocations of the
      knee. Case report].
AB  - INTRODUCTION: Vascular lesion associated with knee dislocation represents a
      common and potentially devastating complication. A delay in revascularization
      that exceeds 8 hours can lead to amputation of the extremity. Therefore it is
      mandatory to do an immediate examination and an effective diagnosis to rule out
      this complication. CASE REPORT: A 19-year-old male was struck by a motor vehicle
      and caused traumatic dislocation of the left knee as observed on X-rays. The knee
      was reduced immediately. At 12 hours, the patient presented edema on the
      extremity and was then stabilized with external fixators. On the third day the
      patient developed a compartmental syndrome and artery obstruction, and required
      fasciotomies and revascularization of the popliteal artery. Twenty four hours
      later, again the artery was obstructed, conducing to supracondylar amputation.
      DISCUSSION: The purpose of this article is to show that a knee dislocation, with
      vascular complications, may lead to extremity amputation as a drastic treatment.
      It is important to emphasize that vigilance of vascular permeability has to be
      followed every 2-3 hours, for at least 72 hours after the injury, and assisted
      with Doppler study. And if needed, at the moment when a pulse abnormality is
      detected an arteriography study must be realized.

PMID- 18826086
TI  - [Complex sacral fracture treated with dynamic compression plates; a case report].
AB  - INTRODUCTION: Sacral fractures are uncommon injuries; published cases constitute
      less than 1% of all the spinal fractures. The vertical sacral fractures are more
      common. Based on Denis's classification for sacral fractures, those that present
      on area III, transverse, are still the less frequent ones and they are associated
      in 57% to a neurological deficit. They are link with high energy trauma. A delay
      in diagnosis and treatment can lead to neurologic deterioration and pain. CASE
      PRESENTATION: A 16-years-old boy fell from a moving vehicle, and suffered direct
      trauma to the dorsal and sacral region. He was initially assisteed in a second
      level hospital unit for lumbar pain, inability to walk and was unable to urinate;
      4 days later to the accident he was transferred to our institution where we
      carried out diagnostic protocol finding a high transverse displaced fracture at
      S2 level with associated neurological deficit. We carried out surgical procedure,
      which consisted on open reduction, with a posterior approach, descompressive
      laminectomy and fixation with dynamic compression plate (D.C.P.) 4.5 mm in
      diameter. Six weeks after the surgical procedure the patient was able to walk
      with partial support, clear improvement in strength and sphincter control.
      DISCUSSION: Transverse fractures of the sacrum are uncommon fractures; still in
      trauma centers the experience is limited. At the moment there is no consensus
      between conservative or surgical tretment modalities according the type of sacral
      fracture. CONCLUSION: Today's evidence suggests that consideration must be taken
      on the risk of a neurological lesion associated through the surgical
      stabilization in comparison to the stability of the fracture site.

PMID- 18826087
TI  - [Sir Robert Jones (1857-1933)].

PMID- 18826088
TI  - [Surgical treatment in otogenic facial nerve palsy].
AB  - OBJECTIVE: To study the character of facial nerve palsy due to four different
      auris diseases including chronic otitis media, Hunt syndrome, tumor and physical
      or chemical factors, and to discuss the principles of the surgical management of
      otogenic facial nerve palsy. METHODS: The clinical characters of 24 patients with
      otogenic facial nerve palsy because of the four different auris diseases were
      retrospectively analyzed, all the cases were performed surgical management from
      October 1991 to March 2007. Facial nerve function was evaluated with House
      Brackmann (HB) grading system. RESULTS: The 24 patients including 10 males and 14
      females were analysis, of whom 12 cases due to cholesteatoma, 3 cases due to
      chronic otitis media, 3 cases due to Hunt syndrome, 2 cases resulted from acute
      otitis media, 2 cases due to physical or chemical factors and 2 cases due to
      tumor. All cases were treated with operations included facial nerve
      decompression, lesion resection with facial nerve decompression and lesion
      resection without facial nerve decompression, 1 patient's facial nerve was
      resected because of the tumor. According to HB grade system, I degree recovery
      was attained in 4 cases, while II degree in 10 cases, III degree in 6 cases, IV
      degree in 2 cases, V degree in 2 cases and VI degree in 1 case. CONCLUSIONS:
      Removing the lesions completely was the basic factor to the surgery of otogenic
      facial palsy, moreover, it was important to have facial nerve decompression soon
      after lesion removal.

PMID- 18826089
TI  - [Computer assisted application of mandarin speech test materials].
AB  - OBJECTIVE: To design an intelligent speech test system with reliability and
      convenience using the computer software and to evaluate this system. METHODS:
      First, the intelligent system was designed by the Delphi program language.
      Second, the seven monosyllabic word lists recorded on CD were separated by Cool
      Edit Pro v2.1 software and put into the system as test materials. Finally, the
      intelligent system was used to evaluate the equivalence of difficulty between
      seven lists. Fifty-five college students with normal hearing participated in the
      study. RESULTS: The seven monosyllabic word lists had equivalent difficulty (F =
      1.582, P > 0.05) to the subjects between each other and the system was proved as
      reliability and convenience. CONCLUSIONS: The intelligent system has the
      feasibility in the clinical practice.

PMID- 18826090
TI  - [Local response caused by implant after cochlear implantation].
AB  - OBJECTIVE: To approach the incidence rate, symptoms, etiologies, correlating
      reasons, consequences and treatments of local responses caused by implant after
      cochlear implantation and to provide reference for the future works. METHODS:
      From 1995 to 2007 there were 997 cases adopted cochlear implantation in Peding
      Union Medical College Hospital. Ten cases experienced local responses were
      analyzed retrospectively. RESULTS: The incidence of local response was 1.003%.
      There were 6 males and 4 females. The ages were between 13 months to 8 years old.
      The average age was 34 months. The devices mainly were made by Cochlear and Med
      EL companies. The mainly symptoms and signs were local swellings, complaint of
      pruritus after ear, decrease of sound legibility and so on. Onset frequencies of
      this disease was 1 to 8 times. The bacterium cultured of displacing liquids was
      negative. But the IgE was detected in 2 cases. Results showed the patients were
      midrange status of hypersensitivity. Positive conservative treatments must be
      done including antibiotics, antihistamines, necessarily using immunotherapy.
      CONCLUSIONS: Besides local infection of bacteria, the allergy caused by silicone
      of implant coupled be a reason. Although the diagnose of this disease was
      difficult, but the screening of source of hypersensitivity was necessary before
      operation. It was recurrent attacks and maybe liable by kindred patients. Onset
      age was more below 4 years old. The patch test should be done again when the
      symptoms were occurrence after operation. If severe secondary infection was
      occurred and the states could not be well controlled the devices in the body must
      be explanted immediately. When the conditions were stable reimplantation could be
      experienced by non-sensibilisinogen devices.

PMID- 18826091
TI  - [Clinical research on delayed traumatic epistaxis and pseudoaneurysm].
AB  - OBJECTIVE: To explore the diagnosis and treatment of delayed traumatic epistaxis
      and put forward a concept of arteriola pseudoaneurysmal epistaxis originated from
      maxillofacial medium-sized artery. METHODS: The clinical data of 53 patients who
      had the typical symptoms of delayed traumatic epistaxis and received digital
      subtraction angiography examination and treated in recent 10 years were
      retrospectively analyzed. RESULTS: Among the 53 patients, 8 patients suffered
      from interval carotid artery pseudoaneurysm. For these 8 patients, 1 died of
      massive epistaxis before embolization, 7 received transcatheter arterial
      embolization( 6 cured and 1 died). Twenty patients suffered from traumatic
      carotid cavernous fistula, all were cured with endovascular occlusion by
      detachable balloon. Twenty-five patients suffered from maxillofacial artery
      hemorrhage. For these 25 patients, 21 were treated by transcatheter arterial
      embolization with gelatin sponge and coils, 4 by anterior ethmoidal artery
      ligation. The followed-up ranged from 6-72 months (median 5 years). All patients
      were successfully treated without serious complications and recurrent hemorrhage,
      except one patient who had recurred hemorrhage three weeks after transcatheter
      arterial embolization. This patient was again successfully treated by artery
      ligation. CONCLUSIONS: Interval carotid artery pseudoaneurysm, carotid cavernous
      fistula and maxillofacial medium-sized artery and arteriola pseudoaneurysm are
      the main causes of delayed traumatogenic epistaxis. Early diagnosis by digital
      subtraction angiography examination and transcatheter arterial embolization or
      artery ligation are the useful methods to treat delayed traumatic epistaxis and
      pseudoaneurysm.

PMID- 18826092
TI  - [Acoustic characteristics of adductor spasmodic dysphonia].
AB  - OBJECTIVE: To explore the acoustic characteristics of adductor spasmodic
      dysphonia. METHODS: The acoustic characteristics, including acoustic signal of
      recorded voice, three-dimensional sonogram patterns and subjective assessment of
      voice, between 10 patients (7 women, 3 men) with adductor spasmodic dysphonia and
      10 healthy volunteers (5 women, 5 men), were compared. RESULTS: The main clinical
      manifestation of adductor spasmodic dysphonia included the disorders of sound
      quality, rhyme and fluency. It demonstrated the tension dysphonia when reading,
      acoustic jitter, momentary fluctuation of frequency and volume, voice squeezing,
      interruption, voice prolongation, and losing normal chime. Among 10 patients,
      there were 1 mild dysphonia (abnormal syllable number < 25%), 6 moderate
      dysphonia (abnormal syllable number 25%-49%), 1 severe dysphonia (abnormal
      syllable number 50%-74%) and 2 extremely severe dysphonia (abnormal syllable
      number > or = 75%). The average reading time in 10 patients was 49 s, with
      reading time extension and aphasia area interruption in acoustic signals, whereas
      the average reading time in health control group was 30 s, without voice
      interruption. The aphasia ratio averaged 42%. The respective symptom syllable in
      different patients demonstrated in the three-dimensional sonogram. There were
      voice onset time prolongation, irregular, interrupted and even absent vowel
      formants. The consonant of symptom syllables displayed absence or prolongation of
      friction murmur in the block-friction murmur occasionally. CONCLUSIONS: The
      acoustic characteristics of adductor spasmodic dysphonia is the disorders of
      sound quality, rhyme and fluency. The three-dimensional sonogram of the symptom
      syllables show distinctive changes of proportional vowels or consonant phonemes.

PMID- 18826093
TI  - [Value of multi-slice spiral CT in the diagnosis of closed thyroid cartilage
      injury].
AB  - OBJECTIVE: To explore the clinical application and to evaluate the value of multi
      slice spiral computed tomography (MSCT) in closed thyroid cartilage injury.
      METHODS: MSCT scan was performed in 5 patients with closed thyroid cartilage
      injury, and 2D and 3D images reconstructions were achieved after volume data was
      transferred to workstation. RESULTS: In 5 cases, the thyroid cartilage fracture
      was found in left board in 4 patients, in right board in 1 patient. In addition,
      one patient had concurrent cricoid cartilage fracture and another patient had
      laryngotracheal stenosis. These fractures and changes were all visualized by 2D
      and 3D images. Lower window level and window width were helpful to reveal the
      structures of thyroid cartilage. Multi-planar reconstruction (MPR) was superior
      in displaying alignment and displacement of fracture in 4 cases. 3D-volume
      reconstruction (3D-VR) was accurate in displaying space change of cartilage
      structures. In 3 cases, the evaluation of 3D-VR was accurate in assessing the
      length, width and shape of fracture, providing helpful data for the clinician to
      adopt the optimal management Computed tomography virtual laryngoscope (CTVL)
      helped to offer the criterions to the diagnosis of upper airway stricture and the
      location of laryngotracheal stenosis in one case. CONCLUSIONS: MSCT was useful in
      the diagnosis and management of closed thyroid cartilage injury and the
      laryngotracheal stenosis. It was believed that the reasonable use of the
      reprocessing technique plays an important role in the diagnosis, treatment and
      evaluation of the effect of closed thyroid cartilage injury.

PMID- 18826094
TI  - [Sonographically guided percutaneous ethanol injection for therapy of thyroid
      benign lesion].
AB  - OBJECTIVE: To develop the microtrauma therapy for thyroid benign lesion, to
      evaluate efficacy of sonographically guided percutaneous ethanol injection for
      therapy of thyroid benign lesion. METHODS: Thirty-two patients with thyroid
      benign lesion were treated in Cancer Hospital, the patients had thyroid disease
      with cystic or cystic and solid nodule without heart and lung disease, and no
      allergy to ethanol, but the most diameter was below 3 cm for the solid disease.
      These patients were divided into two groups, the first group were 14 patients
      (from June 2002 to August 2003), the second group was 18 patients (from September
      2003 to March 2006). The mean injection times was four (1-6) in the first group,
      the volume of each ethanol injection made the absolute ethanol well-distributed
      and kept slight compression intralesional for five minutes for solid disease.
      Partial liquid was extracted for cystic disease first, and 2-10 ml ethanol was
      injected into cyst, the internal time between two punctures was one week. Each
      patient received six times ethanol injection in the second group, ethanol
      injection was same with the first group. The mean follow-up was 29 (12-57)
      months. RESULTS: The efficacy rate was 100.0%, the cure rate was 69.2% in the
      first group. The efficacy rate was 100.0%, the cure rate was 77.8% in the second
      group. There was no significant difference in the cure rate between the groups
      (chi2 = 0.0258, P > 0.05). During follow-up, ultrasound revealed no recurrence
      for the cured patients and no growth for the remnant lesion. Its complications
      were transient after the procedure, no severe complications occurred.
      CONCLUSIONS: Sonographically guided percutaneous ethanol injection should be
      simple, effective, and safe for the thyroid benign lesion, it is easy popularized
      and may has the effect of cosmetology and microtrauma.

PMID- 18826095
TI  - [Treatment of desmoid tumour in head and neck].
AB  - OBJECTIVE: To find out the suitable therapy for the patient of desmoid tumour in
      head and neck. METHODS: Forty-four patients with desmoid tumours of the head and
      neck treated at Cancer Hospital of Fudan University between 1987 and 2002 were
      identified from inpatient tumour database. Patients were classified into three
      groups: operation group (15 cases); operation + radiation group (12 cases);
      radiation group (17 cases). All patients were prospectively followed.
      Clinicopathologic features and treatment modalities were evaluated. RESULTS: In
      the group of operation, four of operation group had recurrences 26.7% (4/15). In
      the group of radiation, three of radiation group had recurrences 17.6% (3/17).
      And the recurrence of operation + radiation group was 23.5% (4/17). No patient
      died of their disease. CONCLUSION: For desmoid tumors of the head neck, operation
      + radiation was recommended, and the benefits of radiation therapy were
      demonstrated.

PMID- 18826096
TI  - [Association between genetic polymorphisms in methylenetetrahydrofolate reductase
      and risk of laryngeal squamous cell carcinoma].
AB  - OBJECTIVE: To determine whether genetic variations in methylenetetrahydrofolate
      reductase (MTHFR) are associated with the risk of laryngeal squamous cell
      carcinoma (LSCC) in a Chinese population. METHODS: Two hundred and seven cases
      with LSCC and 400 matched health controls were genotyped for the MTHFR 677C > T
      and 1298A > C polymorphisms by PCR-restriction fragment length polymorphism (PCR
      RFLP) methods. The relation between these genotypes and risk of LSCC and gene
      environment interaction were analyzed. The adjusted odds ratios (OR) and 95%
      confidence intervals (CI) were calculated by using unconditional Logistic
      regression model. RESULTS: The individuals with 677CT and 677TT genotype had a
      1.66-fold (95% CI 1.08-2.52) and 3.35-fold (95% CI 2.07-5.54) increased risk of
      developing LSCC compared with those who had 677CC genotype. The individuals with
      MTHFR 1298A > C genotype was not significantly different between the two groups.
      Furthermore, cigarette smoking was also found to interact with MTHFR 677C > T
      polymorphism in increasing the risk to LCSS further demonstrating the role of
      gene-environment interaction in development of LSCC. CONCLUSIONS: These findings
      suggested that the MTHFR 677C > T polymorphism may contribute to the risk of
      developing LSCC among Chinese population.

PMID- 18826097
TI  - [Uptake and accumulation of gentamicin by mouse hair cells from the cochlear
      explants in vitro].
AB  - OBJECTIVE: To investigate the upstaging and accumulation of gentamicin by mouse
      hair cells in vitro. METHODS: Cochlear explants were prepared from the
      microdissected neonatal mouse cochlea. Cochlear explants were cultured with
      gentamicin-Texas-red conjunction (GTTR) for different time. Laser confocal
      microscopy was used to observe the distribution of GTTR in the cochlear sensory
      cells after labeling with phalloidin-alexa-488. RESULTS: Soon after culture,
      there was diffuse red staining all tissue cells in the explants. At later time
      the hair cells were more staining than other cells in the explants. There was no
      obviously accumulation of GTTR in the supporting cells. The peak level of
      fluorescent density was reached at 24 hours culture. The GTTR was seen in the
      infracuticular zone of the hair cells. There was still accumulation of GTTR in
      the hair cells of the explants after 7 days culturing. CONCLUSIONS: GTTR and
      cochlea explants were useful methods to investigate the pharmacokinetics and
      mechanisms of gentamicin accumulation over time.

PMID- 18826098
TI  - [Establishment and significance of the experimental minimal persistent
      inflammation models in allergic rhinitis guinea pigs].
AB  - OBJECTIVE: To develop an animal model of minimal persistent inflammation (MPI) in
      allergic rhinitis guinea pigs and to investigate its significance. METHODS: Sixty
      male Hartley guinea pigs were divided into four groups: group A (positive control
      group), B (MPI model group), C (negative group) and D (bland group) respectively,
      with fifteen animals in each group. Guinea pigs from group A, B and C were
      sensitized intraperitoneally by injection of suspension of ovalbumin (OVA) and
      aluminum hydroxide in 0.9% physiological saline. Then, repeated local booster
      sensitization with different concentration of OVA suspension (1% and 0.01%) or
      physiological saline into the nasal cavity of those guinea pigs were performed.
      For group D, physiological saline was used only. Symptoms (sneezing) of guinea
      pigs after antigen challenge were observed and the infiltration of eosinophils
      (EOS) together with the expression of intercellular adhesion molecule 1 (ICAM-1)
      in the nasal epithelial cells were also examined. RESULTS: When challenged with
      1% OVA, the sneezing number of guinea pigs in group B was increased markedly than
      that in group D (P < 0.05). However, there was no difference between group B, A
      and C (P > 0.05). When challenged with 0.01% OVA, the symptom of sneezing almost
      disappeared in group B just like that in group D and there was no difference
      between the two groups (P > 0.05). Besides, there was still more EOS infiltrated
      in the nasal mucosa of guinea pigs in group B than that in group D (P < 0.05).
      There was no expression of ICAM-1 in nasal epithelium of guinea pigs in group D,
      nevertheless, ICAM-1 was found mildly expressed in group B. CONCLUSIONS: MPI
      models have been established successfully through long term challenge with lower
      density of OVA in the sensitized guinea pigs, which will provide us with a new
      method for further research in the mechanism and treatment of allergic rhinitis.

PMID- 18826099
TI  - [Effect of garlicin on the serum levels of interleukin 4 and interferon gamma in
      allergic rhinitis model in rats].
AB  - OBJECTIVE: To investigate the effect of garlicin on the levels of interferon
      gamma (INF-gamma) and interleukin 4 (IL-4) in blood of allergic rhinitis rat
      model. METHODS: Thirty healthy female SD rats were randomly divided into 3
      groups: control group, negative control group and experimental group, 10 rats for
      each group. Ten rats (experimental group) were sensitized and intranasally
      challenged by ovalbumin, aluminium hydroxide hydrate gel and Bordetella pertussis
      inactive microorganism suspension adjuvants, as allergic rhinitis models, and
      then injection of garlicin(0.4 ml) intraperitoneally per day for 10 days. Control
      group rats were immunized as experimental group, and then injection of
      physiological saline as equal volume as garlicin. Negative control group rats
      were investigated using physiological saline. Blood of intrajugular vein of rat
      was extracted for separated plasma Enzyme liked immunosorbent assay (ELISA) was
      utilized to detect the serum levels of IL-4 and IFN-gamma. RESULTS: The serum
      levels (x +/- s) of IL4 were (22.81 +/- 8.79) pg/L, (41.43 +/- 4.93) pg/L, (9.93
      +/- 2.07) pg/L, and those of IFN-gamma were (22.32 +/- 11.20) pg/L, (11.35 +/-
      2.45) pg/L and (21.69 +/- 5.93) pg/L, respectively, among experimental group,
      control group and negative control group. The serum level of IL-4 in experimental
      group rats was lower than value of control group rats (t = 3.22, P < 0.05), while
      higher than negative control group (t = 4.17, P < 0.05). The serum level of IFN
      gamma was increased significantly in experimental group rats with significant
      difference when compared with value of control group rats (t = 3.84, P < 0.05),
      while no difference was shown between experimental group and negative control
      group (t = 1.47, P > 0.05). CONCLUSIONS: Garlicin could increase serum level of
      INF-gamma and decrease serum level of IL4 significantly in allergic rhinitis rat
      model. It played an important role on regulating serum levels of cytokines of Thl
      and Th2.

PMID- 18826100
TI  - [A case report of auricular neurilemmoma].

PMID- 18826101
TI  - [Transient receptor potential melastatin 7 channel protein in human head and neck
      carcinoma cells and role in cell proliferation].
AB  - OBJECTIVE: To detect the presence of ion channel protein and its role in cell
      growth and proliferation in human head and neck squamous carcinoma cells (SCC).
      METHODS: Human head and neck squamous carcinoma SCC-25 cell line was tested with
      transient receptor potential melastatin 7 (TRPM7) antibody using the method of
      immunocytochemistry. The role of TRPM7 in cell growth and proliferation was
      evaluated through its blockade by ion channel blockers and specific siRNA using
      lactate dehydrogenase (LDH) assay technique. RESULTS: Clear immunoreactivity
      against TRPM7 was detected in almost all SCC-25 cells tested, whereas no
      immunoreactivity was observed in negative control. The inhibitory effect of Gd3+,
      a non-specific ion channel blocker, on cell growth and proliferation was potent.
      Addition of 10 micromol/L Gd3+ (n = 16) and 100 micromol/L Gd3+ (n = 16) in the
      culture medium significantly inhibited the growth of SCC-25 cells, as compared
      with control cells growing in normal medium (t was 4.1414 and 6.2661, P was
      0.0256 and 0.0082 respectively). However, the effect of 2-APB was striking. Cell
      proliferation was almost totally suppressed in the presence of 100 micromol/L 2
      APB (t = 13.4493, P = 0.0008, n = 16) compared with cells growing in normal
      medium. Suppression of TRPM7 expression by siRNA also significantly inhibited the
      growth and proliferation of these cells (t = 4.3446, P = 0.0002, n = 32, compared
      with nontransfected cells),whereas cells transfected with negative control siRNA
      showed no difference in cell proliferation compared with nontransfected cells.
      CONCLUSIONS: All of those results strongly suggest the existence of TRPM7 channel
      in human head and neck squamous carcinoma cells. Ion channel blockers serve as a
      potent inhibitor of SCC-25 cell proliferation. The striking inhibitory effect of
      2-APB on cell growth and proliferation may promise clinical workers an inspiring
      remedy for fighting against carcinoma.

PMID- 18826102
TI  - [Proteasome inhibitor bortezomib sensitizes Hep-2 human laryngeal squamous cell
      carcinoma cells to ionizing radiation in vitro and in vivo].
AB  - OBJECTIVE: To determine if proteasome inhibitor bortezomib leads to enhanced
      radiation sensitivity of Hep-2 human laryngeal cancer cells and the relative
      mechanisms. METHODS: Hep-2 cells with or without bortezomib were irradiated at 0,
      2, 4, 6, 8, and 10 Gy. Growth and clonogenic survival data were obtained to
      assess effects of treatment on radiosensitization. In vitro results were tested
      in vivo using a Hep-2 xenograft model. Nuclear factor-kappaB (NF-kappaB)
      activation was determined by Trans AM NF-kappaB P65 kit. The distribution of cell
      cycle and apoptosis were evaluated by flow cytometry. Morphological evidence of
      apoptotic cells were observed with Hochest 33342. RESULTS: It decreased cell
      growth and clonogenic survival. A 34% increase in radiosensitivity was observed
      for cells treated with bortezomib and radiation. Enhancement factor (EF) was 1.46
      in Hep-2 xenografts receiving radiation and bortezomib. NF-kappaB activation was
      induced by radiation and inhibited by pretreatment with bortezomib, and was in a
      dose-dependent manner (r = 0.989, P < 0.05). Hep-2 cells treated with 100 nmol/L
      Bortezomib were arrested at G2-M phase (t = 22.31, P = 0.000) and resulted in all
      increased apoptosis with and without irradiation (P < 0.01). Morphological
      evidence of apoptotic cells could be distinguished under the fluorescence
      microscope after staining with Hochest 33342. Many nuclear fragments were
      observed in Hep-2 cells with bortezomib. CONCLUSION: Bortezomib could enhanced
      the radiosensitivity of Hep-2 laryngeal cancer cells by regulation of the
      distribution of cell cycle.

PMID- 18826103
TI  - [Neoplasty of multiple cerebrospinal fluid rhinorrhea on combined frontal-nose
      approach through endoscope].

PMID- 18826104
TI  - [An integrated management value of pre- and post-otolaryngology surgery in the
      aged patients].

PMID- 18826105
TI  - [Diagnosis and treatment of otorhinolaryngologic teratoma].

PMID- 18826106
TI  - [Analysis of one case with post-uvulopalatopharyngoplasty pulmonary embolism].

PMID- 18826107
TI  - [Primary nasal tuberculosis: report of two cases].

PMID- 18826108
TI  - [Two cases of clicking in the throat].

PMID- 18826109
TI  - [Primary malignant lymphoma of the larynx: a report of two cases].

PMID- 18826110
TI  - [Mitochondrial DNA haplotype and mutations related with aminoglycoside-induced
      deafness].

PMID- 18826111
TI  - [Antihistamines and antileukotrienes in the treatment of allergic rhinitis].

PMID- 18826112
TI  - [Evidence-based pharmacological management of allergic rhinitis].

PMID- 18826113
TI  - [Correlation between subjective assessment and objective measurement of nasal
      obstruction].
AB  - OBJECTIVE: To investigate the correlation between subjective assessment from
      clinician and patients and the objective measurement from active posterior
      rhinomanometry and acoustic rhinometry. METHODS: Clinician and patients'
      assessment of nasal patency was achieved by visual analogue scale (VAS).
      Objective measurement included active posterior rhinomanometry and acoustic
      rhinometry. The mean of clinician's assessment and patients' VAS was compared by
      using paired-samples t-test. The correlation between unilateral nasal airflow
      resistance and unilateral nasal airway volume, unilateral minimal cross section
      area, and also subjective assessment and objective measurement of nasal patency
      were analysed by using Spearman correlation analysis in total patients. RESULTS:
      In total of 316 patients, pre-decongestion and post-decongestion, unilateral
      nasal airflow resistance and unilateral nasal airway volume, unilateral minimal
      cross section area had significant negative correlation respectively (P = 0.000).
      The mean of clinician's assessment and patients' VAS had significant difference
      (P < 0.001) before and after decongestion. Clinician's assessment had significant
      positive correlation with patients' VAS, nasal airflow resistance, and
      significant negative correlation with nasal airway volume, minimal cross section
      area of nasal cavity before and after decongestion (P = 0.000). Patients' VAS had
      significant positive correlation with nasal airflow resistance, and significant
      negative correlation with nasal airway volume, minimal cross section area of
      nasal cavity before and after decongestion (P = 0.000). The correlation
      coefficients from clinician's assessment and objective measurements were greater
      than those from patients VAS and objective measurements. CONCLUSIONS: The
      parameter of active posterior rhinomanometry had significant negative correlation
      with the parameters of acoustic rhinometry. Clinician assessment of nasal patency
      had significant positive correlation with patients' VAS; both of them had
      significant correlation with the parameters of rhinomanometry and acoustic
      rhinometry. Clinician's assessment was more objective and reliable to the
      parameters of objective measurement than patients' VAS.

PMID- 18826114
TI  - [Significance of the examination of path between eosinophils in peripheral blood
      and marrow stem cells for evaluating the effect of hormone therapy in patients
      with allergic rhinitis].
AB  - OBJECTIVE: By means of the detection of the numbers of CD34(+) cells and
      eosinophils (EOS), and the level of IL-5 in peripheral blood from normal controls
      and patients with allergic rhinitis pre- or post-treatment, the role of EOS-stem
      cells paths for treatment effect in allergic rhinitis (AR) was studied so as to
      find the convenient and quick indicators which could be used to evaluate the
      clinical therapeutic effect and adjust the methods of the hormone therapy.
      METHODS: There were 2 groups. (1) experimental group: 44 patients, including 24
      males and 20 females with a age range of 7 to 68 years old. The patients received
      the treatment of fluticasone spurt for four weeks. (2) CONTROL GROUP: 30 cases,
      from normal health examination. The EOS numbers, CD4(+) cell numbers and the IL-5
      level were examined in control group as well as before and after therapy in
      experimental group. RESULTS: The IL-5 level and CD numbers before therapy in
      experimental group were (88.25 +/- 33.47) ng/L, (9.24 +/- 2.15)/10(5),
      significantly higher than that after therapy and experimental group which were
      (44.34 +/- 16.32) ng/L, (6.31 +/- 1.83)/10(5) and (31.24 +/- 8.43) ng/L, (3.47 +/
      1.32)/10(5) respectively. The IL-5 level was positively correlated with the
      CD34(+) number pre-and post treatment in experimental group (r = 0.64, P <0.01;
      (r = 0.61, P <0.01). The EOS number was positively correlated with the level of
      IL-5 (r = 0.64, P <0.01). CONCLUSIONS: IL-5 and CD34(+) cells can be regarded as
      indicators to evaluate the therapeutic effect. The EOS, CD34(+) cells and the
      level of IL-5 in the peripheral blood are correlated with the pathogenesis of AR,
      suggesting that there is a related path between the local nasal tissue of AR
      patients and the marrow.

PMID- 18826115
TI  - [Association of single nucleotide polymorphisms of GATA3 with allergic rhinitis
      phenotypes in Chinese].
AB  - OBJECTIVE: To evaluate the association between single nucleotide polymorphisms
      (SNP) of GATA3 and Chinese with allergic rhinitis. METHODS: This study included
      109 patients with allergic rhinitis and 112 healthy control people. SNP of two
      loci with restriction fragment length polymorphism was detected, rs1269486 at
      promoter region and rs2229360 located 92 bp downstream of STOP codon. Total IgE
      and specific IgE of Der p and Der f with different genotypes of the two loci were
      compared. RESULTS: There was SNP at both loci of rs1269486 and rs2229360. The
      genotypes of rs1269486 were GG, GA and AA, and the genotypes of rs2229360 were
      CC, CT and TT. The frequency of genotype GG and allele G in patient group was
      significantly higher than that in control group (chi2 = 13.75, P <0.01; chi2 =
      12.91, P <0.01), and the frequency of genotype GA and allele A in patient group
      was significantly lower than that in control group (chi2 = 11.90, P <0.01; chi2
      =12.91, P <0.01). There were no significant differences between patient group and
      control group for the frequencies of genotypes and alleles at rs2229360 (P >
      0.05). The haplotype frequency of GC in patient group was significantly higher
      than that in control group (chi2 = 114.59, P < 0.01), and the haplotype frequency
      of AC in patient group was significantly lower than that in control group (chi2 =
      87.52, P <0.01). There was no significant difference of the levels of serum total
      IgE and specific IgE to Der p and Der f with the genotypes at the two loci (P
      >0.05). CONCLUSIONS: The SNP at rs1269486 of GATA3 is associated with allergic
      rhinitis in Chinese.

PMID- 18826116
TI  - [Effects of minimal persistent inflammation on nasal mucosa of experimental
      allergic rhinitis in guinea pigs].
AB  - OBJECTIVE: To establish an animal model of minimal persistent inflammation (MPI)
      of allergic rhinitis in guinea pigs and to investigate the changes of nasal
      mucosa. The expression of transforming growth factor-beta1 (TGF-beta1) and matrix
      metalloproteinases-9 (MMP-9) were discussed. METHODS: Thirty male Hartley guinea
      pigs were randomly divided into two groups: MPI model group and control group
      randomly, with fifteen animals in each group. Guinea pigs from MPI model group
      were sensitized intraperitoneally by injection of suspension of ovalbumin (OVA)
      and aluminum hydroxide in 0.9% physiological saline. Then, repeated local booster
      sensitization with low concentration of OVA suspension into the nasal cavity was
      performed to establish MPI models. Alcian blue-periodic acid-Schiff (AB-PAS)
      staining and Masson's trichrome (MT) staining were used to determine the number
      of goblet cells and collagen deposition within the basement membrane of
      epithelium. The expression and distribution of TGF-beta1 and MMP-9 in nasal
      mucosa were estimated by double immunofluorescence under a confocal laser scan
      microscopy system. RESULTS: Compared with the control group, the increased goblet
      cells (t = 13.720, P < 0.05) in nasal epithelium together with the increased
      collagen fibrils (t = 4.542, P <0.05) within the basement membrane of epithelium
      were observed in the MPI model group. There was nearly no expression of TGF
      beta1, in the control group and the expression of MMP-9 was only found in the
      epithelium cell. In contrast, there was significantly higher expression of TGF
      beta1 and MMP-9 (t = 25.218, P <0.05) in nasal mucosa of MPI model group than
      that in control group. TGF-beta1 mainly expressed in the epithelium cell, the
      infiltrated inflammatory cell and extracellular matrix, while MMP-9 expressed in
      the epithelium cell and the infiltrated inflammatory cell. CONCLUSIONS: Long time
      MPI in allergic rhinitis resulted in some changes of tissue remodeling in nasal
      mucosa. TGF-beta1 and MMP-9 may play an important role in disease progression.

PMID- 18826117
TI  - [Expression and significance of galectin-3 and galectin-9 in mice nasal mucosa
      with allergic rhinitis].
AB  - OBJECTIVE: To evaluate the expression of galectin-3 and galectin-9 in mice nasal
      mucosa,and to explore the role of galectin-3 and galectin-9 in allergic rhinitis
      (AR). METHODS: Twenty mice were randomly divided into AR group and control group,
      10 mice in each group. Ten mice of BALB/c were sensitized intraperitoneally with
      10 microg of ovalbumin(OVA) adsorbed onto 2 mg Al(OH)3 on day 1 and day 14. Mice
      was induced daily by intranasal daily administration of 10 microl of saline
      containing 100 microg of OVA from day 21 to day 28. OVA was replaced with saline
      in control group. Immunohistochemical staining was used to examine the expression
      of galectin-3 and galectin-9 in nasal mucosa. RT-PCR was performed to investigate
      the level of mRNA expression of complement galectin-3, galectin-9. The level of
      IL-4, IL-5 and IFN-gamma in peripheral blood were titrated by ELISA. RESULTS:
      Galectin-3 and galectin-9 were detected in both groups. Expression of galectin-3
      and galectin-9 in group AR was higher than that in control group. Pearson
      correlation analysis demonstrated that the levels of galectin-3 and galectin-9
      were positively correlated with the level of IL-4 and IL-5, but negatively
      correlated with the level of IFN-gamma. CONCLUSIONS: Galectin-3 and galectin-9
      might play an important role in the pathogenesis of allergic rhinitis.

PMID- 18826118
TI  - [Effects of sulphur dioxide inhalation on allergic rhinitis in mice].
AB  - OBJECTIVE: To observe the effect of sulphur dioxide (SO2) inhalation on the
      pathogenesis of allergic rhinitis (AR) in mice, and investigate the toxic effect
      of SO2 on respiratory tract mucosa. METHODS: Fifty male Kunming strain mice were
      randomly allocated to five groups, i. e., control group, AR group and AR plus
      different concentrations of SO2 group (three sub-groups). Nasal cavity irrigating
      solution was gathered from nasal cavity, and blood from the orbital venous sinus
      after anesthesia The concentrations of IL-5 and IL-13 in the peripheral serum and
      nasal cavity irrigating solution were measured by ELISA. The number of
      eosinophils (EOS) per square millimeter in sinus mucosa was calculated by
      hematoxylin-eosin. The expression of SP-D in nasal mucosa was analyzed by
      immunohistochemistry technique. RESULTS: With increasing concentrations of SO2,
      the levels of IL-5 and IL-13 in the peripheral serum, and the density of Eos in
      sinus mucosa increased simultaneously. A positive correlation existed between the
      concentration of inhaled SO2 and the elevation of both IL-5, IL-13 and Eos
      infiltration in nasal mucosa. The coefficient correlation relatively were 0.894,
      0.874, 0.894, 0.891 and 0.870 (P <0.01). The expression of SP-D in 56 mg/m3 and
      112 mg/m3 SO2 groups was higher, while it was lower in 168 mg/m3 SO2 group (P <
      0. 001). CONCLUSIONS: The study showed that sulphur dioxide inhalation
      facilitates the onset of allergic rhinitis in mice. SO2-related Th2-derived
      cytokines as well as the infiltration of EOS in nasal mucosa help to aggravate
      the development of allergic rhinitis.

PMID- 18826119
TI  - [Cochlear implantation in the ossified cochlear].
AB  - OBJECTIVE: To explore the problems and describe clinical experiences associated
      with multichannel cochlear implantation in patients with cochlear ossification.
      METHODS: Seven cochlear implant cases with bilateral cochlear ossification from
      1996 to 2006 in Beijing Tongren Hospital were retrospectively reviewed, 4 of
      which were the consequence of meningitis. Three patients' cochlear were
      completely ossified, 1 patient's tympanic scala was completely ossified, 1
      patient's cochlear was partially ossified, and 2 patients' cochlear were
      partially fibrotic. This article addressed the components of the preoperative
      evaluation, surgical decision-making, and specific techniques for cochlear
      implant array insertion in all kinds of ossified cochlea. RESULTS: Gusher was
      found in 1 case but less serious than that with inner ear malformations. The
      electrodes were inserted in the cochleostomy in full length in 4 cases, 1 case
      gave up, and the cochlear implant array were partially inserted in the remains.
      No serious complications occurred after implantation. All patients had auditory
      sensations. The impedance of the electrodes, the T level, C level and the hearing
      threshold were slightly higher than that of the normal cochlear implantation.
      CONCLUSIONS: The key influencing factor of ossified cochlear patients were the
      degree of the disease and whether the electrode implanted completely or not. So,
      the profound sensorineural hearing loss patients after meningitis should be paid
      more attention. Patients with ossified cochlear could be benefit from cochlear
      implantation.

PMID- 18826120
TI  - [Window partial laryngectomy for the treatment of stage T2-3 glottic laryngeal
      carcinoma].
AB  - OBJECTIVE: To investigate the operative effect and value of window partial
      laryngectomy for the treatment of stage T2-3 glottic laryngeal carcinoma.
      METHODS: From Oct. 2000 to Dec. 2006, the stage T2-3 glottic laryngeal carcinoma
      of 48 patients by properly selected were performed with window partial
      laryngectomy and laryngeal reconstruction. Twenty nine males and 19 females were
      included. Their ages ranged from 43 to 78 years (median 57.0 years). Before
      operation and in the 6 months after operation, these targets including auditory
      mental evaluation of hoarse degree, active degree and symmetry of vocal cord,
      glottic width in the time of quiet breathing, glottic closing degree in the time
      of phonating, respiratory function and swallowing function were surveyed. In
      addition, the things of recurrence and metastasis of tumors together with
      survival time of patients were following investigated. RESULTS: All patients were
      decannulated successfully and incisions were healed smoothly. No operative
      complication occurred. Except active degree of vocal cord (P = 0.343), there were
      respectively significant difference between two group targets of auditory mental
      evaluation of hoarse degree (all P <0.01), symmetry of vocal cord (P = 0.000),
      glottic width in the time of quiet breathing (P = 0. 001), glottic closing degree
      in the time of phonating (P = 0.001) and respiratory function (P=0.001) those
      were investigated before operation and after operation. The swallowing function
      wasn't influenced (P= 0.310). There were laryngostenosis in 1 case, recurrence in
      1 case (2.1%), cervical lymph node metastasis in 1 case and hepatic metastasis in
      1 case. Two cases died. 3-year and 5-year overall survival rate were respectively
      96.9% and 88.9%. CONCLUSIONS: The study showed that window partial laryngectomy
      was successful for treating stage T2-3 glottic laryngeal carcinoma by properly
      selected. This operation was effective for reducing surgical invasion and
      beneficial to resume respiratory and vocal function.

PMID- 18826121
TI  - [Correlation between the vascular endothelial growth factor C expression and
      lymph node metastasis in human nasopharyngeal carcinoma].
AB  - OBJECTIVE: To detect the expression of vessel endothelial growth factor C (VEGF
      C) and microlymphatic vessel density (MLVD) and probe the relationship between
      lymphangiogenesis and lymph node micrometastasis in nasopharyngeal carcinoma.
      METHODS: The expression of VEGF-C, was evaluated in 58 cases with nasopharyngeal
      carcinoma and 20 samples of nasopharyngitis tissues by immunohistochemical
      staining SP methods. The MLVD in tumor was counted by immunostaining with the
      specific antibody lymphatic vessel endothelial hyaluronic acid receptor 1 and
      analyzed with clinicopathologic parameters. RESULTS: The positive rate of VEGF-C
      was 84.5% and 15.0% respectively in nasopharyngeal carcinoma and nasopharyngitis
      tissues, there was significant difference between them (chi2 = 32.309, P <0.01).
      The microlymphatic vessel density was (28.6 +/- 6.2) pieces per field and (10.5
      +/- 3.0) pieces per field respectively in nasopharyngeal carcinoma and
      nasopharyngitis tissues, there was significant difference between them (t =
      12.491, P <0.01). The expression of VEGF-C and the MLVD were significantly higher
      in nasopharyngeal carcinoma and in lymph node metastasis group than in no
      metastasis group. The expression of VEGF-C was positively correlated with MLVD (t
      =3.512, P <0.01), lymph node metastasis (chi2 =7.715, P <0.01, r =0.712) and
      clinical stage (chi2 =4.250, P <0.05, r =0.481). CONCLUSIONS: In nasopharyngeal
      carcinoma, the expression rate of VEGF-C was high. VEGF-C expression was
      positively correlated with MLVD and lymph node metastasis and tumor staging. It
      was explained that VEGF-C attached itself to the emergence and infiltration and
      transfer of NPC. There was close correlation between the expression of VEGF-C and
      MLVD. It was explained that the expression of VEGF-C in NPC was correlated to
      neoplasm lymphangiogenesis and that VEGF-C played a vital role in the progression
      of NPC. VEGF-C was likely to a potential target of anticancer therapy.

PMID- 18826122
TI  - [Experimental study on tracheal reconstruction using porous titanium rings and
      free skin flap].
AB  - OBJECTIVE: To investigate the feasibility and efficacy of the cervical tracheal
      reconstruction using porous titanium rings and free skin flap. METHODS: Twelve
      adult mongrel dogs were divided randomly into group I and group lI. A segment of
      cervical trachea (25 mm, 4 rings, about 2/3 circumference) was resected and a
      rectangular free skin flap was harvested from abdomen. The flap was sutured to
      the defect part and supported with two porous titanium rings (group I) or without
      (group II ). X ray and fiberscopic examinations were performed at the end of the
      first and the sixth months postoperatively. After six months the dogs were
      sacrificed and the grafts were examined macroscopically and microscopically.
      RESULTS: In group I, one dog was sacrificed for wound infection and skin flap
      necrosis with deflexion of titanium rings in the fifth day postoperatively. The
      other 5 of 6 survived until the end of six months. X-ray examination showed
      titanium rings were fastened well without displacement or deformity. Through
      fiberscopy, the trachea luminal patency was maintained well without stricture,
      shrinkage or necrosis. Histologic examination showed most of the inner surface of
      the flap was covered with ciliated columnar epithelium. In group II, 3 of 6 dogs
      died of suffocation within 24 hours postoperatively. The remaining 3 dogs
      survived from 7 to 16 days with dyspnea and fiberscopic examination showed
      narrowed trachea lumens. CONCLUSIONS: Porous titanium rings could recreate the
      framework for cervical tracheal reconstruction using free skin flap and would be
      one of the options for tracheal reconstruction.

PMID- 18826123
TI  - [An experimental study of polypropylene combined with flap for trachea
      reconstruction].
AB  - OBJECTIVE: Canine model established for tracheal defect reconstruction, to
      investigate the outcome of tracheal reconstruction with combination of
      polypropylene and flap. METHODS: About 3.5 to 4 centimeter cervical trachea was
      resected and replaced with artificial trachea made from monofilament knitted
      polypropylene and surgical flap. Covered stent was implanted postoperatively.
      Survival period and quality of life were recorded, bronchofibroscopy, X-ray films
      and HE sections were performed. RESULTS: Six dogs survived well and another two
      died. The causes of death were respiratory failure in 1 and infection in another.
      Stenosis of anastomosis in 1 was recorded during survival period. The dogs
      started drinking and eating on the second postoperative day, no dyspnea was
      found. The animals were sacrificed at 2, 4, 8 weeks and 6 months after surgery.
      Soft tissue growth was found in polypropylene net 2 weeks after surgery and more
      at 4 weeks. The polypropylene net was covered completely with soft tissue at 8
      weeks and 6 months postoperatively, the hardness and sustentation degree were
      enhanced following the growth and fibrosis of soft tissue. The squamous
      epithelium and columnar epithelium were observed healing well by HE staining
      method. CONCLUSIONS: One-stage operative artificial trachea made from
      monofilament knitted polypropylene which has good histocompatibility and surgical
      flap is the closer artificial trachea to native trachea. It has a promising
      prospect in clinical use.

PMID- 18826124
TI  - [Clinical usefulness of surgery for deviation of nasal septum with perennial
      allergic rhinitis].

PMID- 18826125
TI  - [Traumatic pneumolabyrinth].

PMID- 18826126
TI  - [One case of extranodal Rosai-Dorfman disease in nasal sinuses].

PMID- 18826127
TI  - [A case report of endoscopic transnasal lysis of impacted musculi rectus
      medialis].

PMID- 18826128
TI  - [A report of single lateral congenital nasal pyriform aperture atresia].

PMID- 18826129
TI  - [Ectopic thymus gland of neck: a case report].

PMID- 18826130
TI  - [Combined type of neurofibromatosis I and II: a case report].

PMID- 18826131
TI  - [Effect of allergen immunotherapy involved with antagonist of Toll like receptor
      9 CpG oligodeoxynucleotides].

PMID- 18826132
TI  - [Clinical application of injection augmentation laryngoplasty].

PMID- 18826133
TI  - [An introduction of allergic rhinitis and its impact on asthma (ARIA) 2008
      update].

PMID- 18826134
TI  - [Biotransformation of furannoligularenone by hairy root cultures of Polygonum
      multiflorum].
AB  - OBJECTIVE: To investigate the biotransformation of furannoligularenone by hairy
      roots of Polygonum multiflorum. METHODS: Furannoligularenone was added to the
      medium of hairy roots of P. multiflorum after precultured for 9 days, then they
      were co-cultured. The products were isolated and identified on the basis of their
      physical chemical properties and spectroscopic data. The T-C curve of
      biotransformation was investigated with HPLC. RESULTS: The hairy roots of P.
      multiflorum transformed the substrate to two products, 3-oxo-eremophila-1,7(11)
      dien-12,8-olide(II) and 3-oxo-8-hydroxy-eremophila-1,7(11)-dien-12,8-olide(III).
      After co-cultured for 3 days, the mole conversion ratio of the substrate reached
      the highest (27.2%). CONCLUSION: It's possible to biotransform
      furannoligularenone by hairy roots of P. multiflorum.

PMID- 18826135
TI  - [Analysis in distribution of Atractylodes lancea at Maoshan regions].
AB  - OBJECTIVE: To Investigate the distribution of Atractylodes lancea at Maoshan
      regions. METHODS: To combine the plot sampling with GIS technology in the
      analysis of distribution and its factors. RESULTS: The biomass of Atractylodes
      lancea was related to the growth of Ouercus serrata var. brevipetiolata, slope
      and humidity. The distribution of Atractylodes lancea which was less in north
      Maoshen region, most in south region, least in middle region. CONCLUSION: The
      main factor of distributing sintuation is the human beings. The leading factors
      in the biomass of Atractylodes lancea are Ouercus serrata var. brevipetiolata and
      slope.

PMID- 18826136
TI  - [Secondary metabolites of a marine actinomycete Streptomyces sp. (No. 195-02)
      from South China Sea].
AB  - The metabolites of a marine streptomyces sp. actinomycete (No. 195-02) were
      studied and eight compounds were isolated from the fermentation liquid,
      structures were elucidated by spectroscopy methods as p-hydroxy-benzonitrile (1),
      2-methyl-furan-3-carboxylic acid(2), furan-2-carboxylic acid (3), cyclo(Phe-Phe)
      (4), cyclo(Leu-Ileu) (5), nicotinic acid (6), 2-(1H-indol-3-yl) acetic acid (7)
      and bis(2-ethylhexyl) phthalate (8). The compounds 1, 3 and 8 were firstly
      isolated from Streptomyces sp., compounds 4 -7 were firstly found from marine
      actinomycetes. Coumpouds 4 and 5 evidently inhibited the growth of cancer cell
      lines hepG2 and hep2 at the concentration of 50 microg/ml.

PMID- 18826137
TI  - [Study on the expressed oil of princes-feather fruit before and after processed
      by GC-MS].
AB  - OBJECTIVE: To compare the chemical compositions in the expressed oil before and
      after processed of princes-feather fruit. METHODS: Making use of the GC-MS to
      compare the chemical composition in the expressed oil before and after processed
      of princes-feather fruit. RESULTS: 4 chemical compounds were detected in the
      expressed oil of the raw and 7 of the processed. But the main chemical compound
      (E, E) 9, 12-Octadecadienoic acid, methyl ester of the raw wosnt detected in the
      processed product. CONCLUSION: Processing drugs has the major effect on the
      chemical composition in the expressed oil of princes-feather fruit.

PMID- 18826138
TI  - [Studies on fingerprints of Bupleurum chinense and vinegar-baked Bupleurum
      chinense from Hubei province].
AB  - OBJECTIVE: To establish the HPLC Fingerprint of Bupleurum chinense from GAP
      provenance of Hubei province Baokang, and discuss the changes before and after
      processing. METHODS: Using HPLC detection method equipped with Hypersil ODS
      column (5 microm, 4.6 mm x 250 mm), using acetonitrile-water as mobile phase
      gradient elution, flow as 1.0 ml/min, UV detector set at 203 nm, column
      temperature was at 25 degrees C. RESULTS: Similarity of processed Bupleurum
      chinense and Bupleurum chinense exceeded 0.95, and there were 13 characteristic
      fingerprints of processed Bupleurum chinense, 15 characteristic fingerprints of
      Bupleurum chinense. CONCLUSION: The HPLC Fingerprint of Bupleurum chinense from
      GAP provenance of Hubei province Baokang are established, and the difference
      between Bupleurum chinense before and after processing is studied initially.

PMID- 18826139
TI  - [Studies on identification of Sedum emarginatum].
AB  - OBJECTIVE: To establish methods for identification of the whole plant of Sedum
      emarginatum Migo. METHODS: Macroscopic and microscopic observation and FTIR
      technique were used to authenticate this crude drug, and the identification
      characteristics were studied. RESULTS: The stem cross section and the whole plant
      powder had some notable micro-characters. The infrared spectras of the samples
      collected in the different habitats and seasons were very consistent with each
      other. CONCLUSION: The results can be used as the evidence for identification of
      this ethnomedicine.

PMID- 18826140
TI  - [Identification on Herba Hyperici Japonici and its adulterant].
AB  - OBJECTIVE: To study the identification of Herba Hyperici Japonici and its
      adulterant. METHODS: Herba Hyperici Japonici and Herba Hyperici graminei were
      identified by traditional and modern identification. RESULTS: Both of them showed
      difference in exterior character, microscope characteristic, TLC, UV and HPLC
      fingerprint graphics. CONCLUSION: The distinct characteristic features reveal
      this study can serve as evidence for the identification of Herba Hyperici
      Japonici.

PMID- 18826141
TI  - [Mass spectrometric analysis of quinazoline alkaloid and limonin from Fructus
      Evodiae].
AB  - OBJECTIVE: To study Mass spectrometry of quinazoline alkaloid and limonin from
      Fructus Evodiae by an electrospray ionization (ESI) tandem mass spectrometry.
      METHODS: The ESI source was set at the positive ionization mode, and the MS1 and
      MS2 spectra of quinazoline alkaloid and limonin were acquired. RESULTS: The main
      fragments of quinazoline alkaloid and limonin from Fructus Evodiae were analyzed.
      CONCLUSIONS: The profiles of fragments will be usefull to set quality criteria
      and to study chemical composition of Fructus Evodiae.

PMID- 18826142
TI  - [Analysis of the volatile oils chemical constituents of roots of Actinidia
      deliciosa].
AB  - OBJECTIVE: To analyze the volatile oils chemical constituents of roots of
      Actinidia deliciosa. METHODS: The volatile oils fraction of roots of Actinidia
      deliciosa. were extracted by water vapor distilling, and then the constituents
      were separated and identified, by GC-MS. RESULTS: 16 compounds were identified,
      accounting for 89.37% of all quantity. CONCLUSION: The principal volatile oils
      chemical constituents are Phenol, 2,4-bis(1,1-dimethylethl)-; 2-Propenoic acid, 3
      (4-methox yphenyl)-, ethyl ester; 9-Octadecenoic acid (Z)-, methyl ester;
      Cyclotetrasiloxane, octamethyl-.

PMID- 18826143
TI  - [Studies on chemical constituents of Syringa veutina].
AB  - OBJECTIVE: To study the chemical constituents of Syringa veutina Kom. METHODS:
      The constituents were isolated and repeatedly purified on silica and Sephadex LH
      20 column chromatography. They were dentified and structurally elucidated by
      spectral analysis. RESULTS: Seven compounds were obtained. They were identified
      as Syningin(1), Liriodendrin(2), (+) -Medioresinol di-O-beta-D-glucopyranosied
      (3), Rutin(4), Quercetin 3-O-beta-D-glucopyranoside (5), Kaempferol-3-O-beta-D
      glucopyranosied (6), D-mannitol (7). CONCLUSION: Compound 2 and 3 were isolated
      from this genus for the first time. Compound 4, 5, 6 and 7 were isolated from
      this plant for the first time.

PMID- 18826144
TI  - [Studies on chemical constituents from flowers of Chrysanthemum indicum].
AB  - OBJECTIVE: To study the chemical constituents of the flowers of Chrysanthemum
      indicum. METHODS: Chemical constituents were isolated and purified by silica gel
      and Sephadex LH-20 column chromatography. The structures were identified by means
      of physico-chemical and spectral data. RESULTS: From the 80% ethanol extract of
      the material, seven compounds were isolated. Their structures were identified as
      acacetin(1), acacetin-7-O-(6"-O-acetyl) beta-D-glucopyranoside (2), linarin (3),
      apigenin-7-O-beta-D-glucopyranoside(4), chlorogenic acid (5), vanillic acid(6)
      and sucrose(7), respectively. CONCLUSION: Compounds 2, 4, 6 and 7 are isolated
      from C. indicum for the first time.

PMID- 18826145
TI  - [The study of dynamic acccumulation of camptothecin in Camptotheca acuminata
      fruit by TLCS].
AB  - OBJECTIVE: To establish TLC scanning method for the determination of camptothecin
      in Camptotheca acuminata fruit, and analysis the dynamic accumulation of
      camptothecin in Camptotheca acuminata fruit to find out the best collection
      period. METHODS: Silica gel H-CMC-Na thin layer plate was adopted in the
      determination with chloroform-acetone (7 : 3) used as deeloper, Single-wavelength
      and linear scanning of TLC was used, and the detection wavelength was 360 nm.
      RESULTS: There was a good linear relationship for Comptothecin within the range
      of 0.0542 - 0.3252 microg, the average recovery was 97.13%, RSD was 1.76%.
      CONCLUSION: The method is accurate, simple and reliable, and can be used for the
      determination of camptothecin in Camptotheca acuminata fruit and dynamic
      accumulation research.

PMID- 18826146
TI  - [The mechanism of resveratrol on anti-hepatoma Bel-7402 and modulating IL-8 in
      tumor model mice].
AB  - OBJECTIVE: To explore the anti-tumor effect of resveratrol on the hepatocellular
      carcinoma cell line Bel-7402 both in vitro and in vivo. METHODS: MTT colorimetry
      was used to measure the tumor cell growth repression rate. The level of Bcl-2 was
      measured by Western blotting. The cell cycle of Bel-7402 and intracellular IL-8
      were analyzed by flow cytometry. The expression of IL-8 mRNA was determined by
      semiquantitative RT-PCR and quantification assay of IL-8 was determined by ELISA.
      RESULTS: Our findings indicated that resveratrol inhibited proliferation, induced
      apoptosis, and influenced cell cycle of Bel-7402 cells at a dose-and time
      dependent manner in vitro. Furthermore, resveratrol could exert a dose-related
      down-regulatory effect on IL-8 in Bel-7402 bearing mice. CONCLUSION: It suggestes
      resveratrol might have chemotherapeutic potential and immunomodulation action to
      Bel-7402 to cellular carcinoma both in vitro and in vivo.

PMID- 18826147
TI  - [Regulative effects of aquaporin 4 expression by rhein in rhubarb to intestinal
      epithelial cell line LoVo].
AB  - OBJECTIVE: To investigate the effects of rhein on regulating aquaporin4 (AQP4) to
      LoVo cells cultured with RPMI-1640 medium containing rhein. METHODS: LoVo cells
      were cultured with RPMI-1640 medium containing different concentration rhein for
      24 hours and were cultured with RPMI-1640 containing rhein (20 mg/L) for
      different time. Four groups were assigned as LoVo cells were cultured
      respectively with RPMI-1640 medium containing different concentration rhein (40,
      20, 10 mg/L and control group), while six groups were assigned as LoVo cells were
      cultured with RPMI-1640 medium containing rhein (20 mg/L) for different time (3,
      6, 12, 24, 48 h and control group). The location of AQP4 protein in LoVo cells
      was definited by immuocytochemistry dying. Western blotting and semiquantitative
      RT-PCR were adopted to detect the relative expression of AQP4 protein and mRNA.
      RESULTS: AQP4 was located mainly in plasma membrane of LoVo cells while partly in
      cytoplasm. The relative expression of AQP4 protein and mRNA decreased with the
      increasing of rhein concentration; there was no significant difference of the
      relative expression of AQP4 in 10 mg/L group compared with that in control group,
      but it decreased significantly in 40 and 20 mg/L groups. The relative expression
      of AQP4 in 3 and 6 h groups was lower than that in control group but there was no
      statistical significance, however that in 12, 24, 48 h groups was lower
      significantly compared with that in control group. CONCLUSION: Rhein can inhibit
      the genetic transcription and the translation of AQP4 gene in LoVo cells, which
      demonstrates that the change of AQP4 expression regulated by rhein may be related
      to the cathartic effect of rhubarb.

PMID- 18826148
TI  - [Study of Scutellaria baicalensis and Baicalin against antimicrobial
      susceptibility of Helicobacter pylori strains in vitro].
AB  - OBJECTIVE: To compare the antimicrobial activities of Scutellaria baicalensis and
      Baicalin against Helicobacter pylori (H. pylori) in vitro. METHODS: The crude
      alcohol extraction of Scutellaria baicalensis was obtained by successive
      extractions with ethanol. Baicalin was extracted by using organic extraction
      methods and the purity was analyzed by high-performance liquid chromatography
      (HPLC). The crude alcohol extraction of Scutellaria baicalensis and Baicalin were
      used in broth dilution assays to test for antibacterial properties. RESULTS: The
      content of Baicalin was 5.01 g from 100 g Scutellaria baicalensis. The purity of
      Baicalin was 96.8%. The crude alcohol extraction of Scutellaria baicalensis and
      Baicalin were tested for their ability to inhibit H. pylori in vitro by using
      broth dilution assays. The MIC50 and MIC90 of Baicalin against ten strains of H.
      pylori were 1.04 and 1.30 mg/ml respectively. The MIC50 and MIC90 of the crude
      product against ten strains of H. pylori were 2.60 and 3.26 mg/ml respectively.
      CONCLUSION: The Baicalin and Scutellaria baicalensis are bactericidal against H.
      pylori. The antimicrobial activity of Baicalin is greater than that of
      Scutellaria baicalensis.

PMID- 18826149
TI  - [Anti-allergic effects of Rubus suavissimus extract].
AB  - OBJECTIVE: To investigate the effects of Rubus suavissimus S. Lee extract (RSE)
      on mice, and its influence on release of histamine from rat peritoneal mast cells
      induced by compound 48/80 in vitro. METHODS: To establish murine delayed-type
      hypersensitive model induced by 2,4-dinitrofluotobenzene (DNFB) and sheep red
      blood cell (SRBC); murine type I allergic reaction induced by PCA, and then to
      observe the anti-allergic effect of RSE. HPLC-ECD methods were performed to
      detect the contents of histamine released from rat peritoneal mast cells induced
      by compound 48/80 in vitro. RESULTS: Compared with the model group, RSE could
      ameliorate the ear swelling and capillary permeability in mice induced by DNFB
      and PCA. RSE also reduced the thickness of the mice hind paw induced by SRBC in
      significant dose-dependent manner. Meanwhile, RSE obviously inhibited the release
      of histamine in rat peritoneal mast in vitro, a dose-dependent manner.
      CONCLUSION: RSE exerts potential anti-allergy effects and the mechanisms may be
      partly related to its inhibitory effect on the release of histamine from mast
      cells.

PMID- 18826150
TI  - [Effect of polysaccharides in crude and processed Cornus officinalis on the
      immunologic function of mice with immunosuppression induced].
AB  - OBJECTIVE: To investigate the effect of polysaccharides in crude and processed
      Cornus officinalis on the immunologic function of mice with immunosuppression
      induced. METHODS: The immunosuppressed mice were induced by Cyclophosphamide. Non
      specific immune function was determined by cleaning carbon particle method.
      Humoral immunity was determined by serum haemolysin formation method. Cellular
      immunity was determined by proliferation and transformation of spleen lymphocyte
      method. RESULTS: The polysaccharides in crude and processed Cornus officinalis
      both markedly increased the carbon particle clearance index K, phagocytic index
      alpha, serum HC50 and proliferation and transformation of spleen lymphocyte,and
      the polysaccharides in processed Cornus officinalis was better than the crude
      one. CONCLUSION: The polysaccharides in crude and processed Cornus officinalis
      have an enhanced effect on non-specific immunity, specific humoral immunity and
      specific cellular immunity in immunodeppressed mice, and after being processed
      with wine, the action of polysaccharides increased markedly.

PMID- 18826151
TI  - [Screening of anti-tumor parts from the seeds of Livistona chinensis and its anti
      angiogenesis effect].
AB  - OBJECTIVE: To screen the anti-tumor active parts from the seeds of Livistona
      chinensis R. Br. and its mechanism of anti-angiogenesis effect. METHODS: MTT
      assay and ELISA were used to detect the proliferation and the secretion of
      vascular endothelial growth factor (VEGF) of chronic myelogenous leukemia K562,
      ovarian neoplasm SKOV3, colon carcinoma HT-29 and bladder cancer T24 cell lines
      respectively. The expression of fetal liver kinase (Flk-1) protein and mRNA in
      endothelial cells induced by VEGF was analyzed by Western blotting and RT-PCR.
      RESULTS: The ethyl acetate part of alcohol extract from seeds of Livistona
      chinensis R. Br. could selectively inhibit the proliferation of HT-29 and T24
      cell lines in a dose-dependent manner, the maximum inhibitory rate were 74.66%
      and 86.52%, and could significantly inhibit the secretion of VEGF protein of the
      four tumor cell lines. The petroleum ether part had similar inhibitory effect as
      well as the ethyl acetate part, but its potency was inferior to the ethyl acetate
      part, the maximum inhibitory rate were 43.80% and 38.67%, the water-soluble and n
      butanol parts had no effect on different tumor cell lines. The ethyl acetate part
      could reduce significantly the expression of Flk-1 protein and mRNA of HUVEC
      induced by VEGF. CONCLUSION: The ethyl acetate part, which is considered as
      active part of alcohol extract from seeds of Livistona chinensis R. Br., has fine
      anti-tumor activity, and its mechanism might be associated with reducing VEGF
      protein secretion and inhibiting the expression of Flk-1 mRNA and protein.

PMID- 18826152
TI  - [Study on quality evaluation of Radix Isatis based on analysis of biothermic
      activity].
AB  - OBJECTIVE: To establish a novel pattern and method to evaluate the quality of
      Radix Isatis based on analysis of biothermic activity. METHODS: Chemical and
      biothermodynamic methods were used and compared to investigate the quality of
      different Radix Isatis samples. And a mathematic model was established by
      computer aided pattern recognition to evaluate the quality of Radix Isatis.
      RESULTS: The quality of Radix Isatis was partially related to the content of
      organic acids and polycose, but it could not be correctly recognized by both
      chemical determination and HPLC fingerprint. On the other hand, the mathematic
      model based on the main four parameters of biothermodynamic analysis was very
      correct (misjudgment ratio of 1.39%) to recognize the quality of Radix Isatis.
      CONCLUSION: The established model in this paper based on analysis of biothermic
      activity is more accurate and reliable than that of chemical methods to evaluate
      the quality of Radix Isatis.

PMID- 18826153
TI  - [Optimization for formulation matrix proportion of xiangyu cataplasm by uniform
      design].
AB  - OBJECTIVE: To optimize the matrix formulation of cataplasm used to cure infantile
      diarrhea. METHODS: The optimum proportion of matrix for the preparation
      technology process of cataplasm was selected by uniform design and SPSS
      regression analysis. A check-up for adhibition , peeling strength, nonflowing,
      content of cream was founded. RESULTS: The best matrix's prescription gelatin:
      CMC-Na: PANA: kaolin: aluminum trichloride: citric acid: PVP K-30: PEG400:
      trimethylene glycol: tween-80 was 0.25 : 0.1 : 0.2 : 1.5 : 0.4 : 0.6 : 0.8 : 2 :
      1 : 0.5. CONCLUSION: The preparation technique of cataplasm is feasible, and its
      quality is steerable, it is a safe and effective transdermal-drug delivery
      system.

PMID- 18826154
TI  - [Study on deproteinization and decoloration in extraction of polysaccharides from
      Rabdosia rubescens].
AB  - OBJECTIVE: To screen the method on deproteinization and decoloration in
      extraction of of polysaccharides from Rabdosia rubescens. METHODS: The effect of
      deproteinization with different methods was evaluated in terms of the ratio of
      protein removing and polysaccharide removing, the decoloration effect was also
      calculated. RESULTS: The deproteinization effect was optimal with TCA method and
      activated carbon also achieved a high decoloration rate. CONCLUSION: The result
      can establish foundation for the further study of the polysaccharides from
      Rabdosia rubescens.

PMID- 18826155
TI  - [Isolation, purification and biological activities of Arnebia euchroma
      glycosaminoglycans].
AB  - OBJECTIVE: To study the methods of extraction, isolation, purification and
      biological activities of Arnebia euchroma glycosaminoglycans (AEG). METHODS: AEG
      was purified by distilled water extraction, ethanol fractionation, Sephadex
      column chromatography. The purity and molecular weight and concentration of AEG
      were measured by HPLC; We divided the experiment into Physiological Saline group
      and the other eight groups with different doses of AEG, established RT-PRC method
      to observe the anti-HPV effect after their actions on the verruca tissues.
      RESULTS: Using HPLC, the group of AEG was divided into two glycosaminoglycans
      with different molecular weight as 27336 and 1152. Bioassay results showed that
      AEG had anti-HPV-DNA activity, the lowest effective concentration was 0.781
      mg/ml. CONCLUSION: AEG extracted by this method is a mixture with two molecular
      weight glycosaminoglycans, and has obvious anti-HPV effect.

PMID- 18826156
TI  - [Study on optimizing extraction methods of Lamiophlomis rotata].
AB  - OBJECTIVE: To optimize different extraction methods of Lamiophlomis rotata Kudo.
      METHODS: With the content of total flavonoids as assay index, the effect of three
      extraction methods was compared and the optimal excracting technology was
      selected by orthogoral test. RESULTS: The contents of flavonoids and solids by
      ethanol extraction were more than that by the boiling water extraction and
      ultrasonic extraction. CONCLUSION: The ethanol extraction is the optimal
      extracting technology, which is to put 10g powder of Lamiophlomis into 200ml 60%
      alcohol, and then reflux extract for 25 min.

PMID- 18826157
TI  - [Clinical study on Shen Shuai Fang in treating chronic renal failure].
AB  - OBJECTIVE: To explore the effect of Shen Shuai Fang in treating Chronic Renal
      Failure (CRF) of deficiency of spleen and kidney with turbid damp and blood
      stagnation symptom. METHODS: 125 patients with CRF of deficiency of spleen and
      kidney with turbid damp and blood stagnation symptom were randomly divided into
      two groups, 75 patients in treatment group were treated with Shen Shuai Fang
      adding western medicine and the other patients in control group were treated only
      with western medicine. We observed the effect and indexes change including renal
      function, Hb, proteinuria, lipid before and after treatment. RESULTS: After six
      months' treatment, the general effective rate in treatment group was 77.33%,
      which was higher than that in control group obviously (44.00%, P < 0.01). So
      treatment group was obviously better than control group on decreasing
      proteinuria, improving renal function, increasing Hb, ameliorating lipid
      metabolism (P < 0.05 or P < 0.01). CONCLUSION: Shen Shuai Fang is effective to
      treat CRF of deficiency of spleen and kidney with turbid damp and blood
      stagnation symptom.

PMID- 18826158
TI  - Development and optimization of T2 weighted methods with reduced RF power
      deposition (Hyperecho-TSE) for magnetic resonance imaging.
AB  - Turbo or fast spin echo (TSE/FSE) techniques with variable flip angles have the
      potential to overcome specific absorption rate (SAR) limitations. Such Hyperecho
      TSE sequences allow for high resolution imaging with full signal-to-noise ratio
      (SNR) compared to standard TSE methods. Initially, a short overview of the two
      basic hyperecho schemes is given. Subsequently, the manuscript focuses on the
      flexible hyperecho approach "TRAPS" (smooth transitions between pseudo steady
      states). Basic criteria for flip angle ramp selection are illustrated. Further
      prerequisites to establish hyperecho methods in a clinical environment such as an
      automatic ramp selection are discussed. A summary of the introduced framework for
      contrast characterization and adaptation for conventional and Hyperecho-TSE
      sequences is presented Finally, recent developments in hyperecho imaging are
      provided

PMID- 18826159
TI  - Inverse treatment planning and integration of segmentation procedures.
AB  - The inverse treatment planning procedure in IMRT consists of two basic tasks, the
      fluence optimization and the segmentation into multi leaf collimator (MLC)
      segments. Both tasks can either be run simultaneously or separated. We focus on
      the latter case. When using such a separation the fluence given by MLC segments
      and the optimized one differ. In the same way the quality of the treatment plan
      decreases. In this paper we discuss two approaches to reduce the negative effect
      of a separation of the fluence optimization from the segmentation procedure. The
      fluence smoothing concept is expected to find solutions with, in a mathematical
      sense, smoother fluences. A mandatory segmentation should then result in less
      segments and less decrease of plan quality. In the second approach we take the
      segments and their weights as input to a second optimization cycle which
      readjusts the weights, so the result is as close to the original demands as
      possible. We demonstrate the two methods using a 7-field plan applied to the
      Quasimodo phantom. The results show that the number of segments can be reduced by
      implementing an additional term to the target function. A penalization of local
      extrema however does not have the expected effect. In all cases, an additional
      reoptimization of the segment weights improved the segmented plans significantly.

PMID- 18826160
TI  - [Radiation risk associated with mammography screening examinations for women
      younger than 50 years of age].
AB  - The target group of the German mammography screening program, conducted according
      to the European guidelines, is clearly defined: all women aged 50 to 69 years
      without evidence of breast cancer are invited to screening mammography every two
      years. In the present study the question was raised whether breast cancer
      screening by means of mammography is--from the point of view of radiation hygiene
      -justified also for women under 50 years of age. Based on current radio
      epidemiological breast cancer studies, the excess lifetime risk (ELR) to incur or
      die from breast cancer of a 40, 45 and 50 year old woman was assessed. Different
      risk models were used to estimate the radiation risk, e.g. models given for the
      "Life Span Study" of the atomic bomb survivors and the risk model given in the
      recent Biological Effects of Ionizing Radiation (BEIR) VII report. The benefit
      risk ratio was defined as the ratio of the number of "saved lives" due to
      screening to the number of deaths due to "radiation induced breast cancer". All
      estimations were based on the assumption that screening is taking place up to the
      age of 69 years, with screening examinations being performed annually up to the
      age of 50 and every two years from the age of 50 onwards. The glandular dose per
      two-view mammography investigation was assumed to be 4 mGy. The benefit due to
      mammography screening was assumed to be 25% for all age groups. Assuming
      screening from the age of 40 or 45 years, the ELR of breast cancer is on average
      about 3.5 or 2 times as high compared to the ELR associated with screening
      starting from the age of 50 years. In comparison to the benefit risk ratio, which
      results for women participating in a mammography screening from the age of 50
      years, the benefit risk ratio for women starting with screening already from the
      age of 40 or 45 years is reduced by a factor of 3 or 2. With the present data-
      with regard to both, the benefit and the radiation risk--it appears not to be
      justified to expose women from the age of 40 years to the additional radiation
      exposure associated with a mammography screening.

PMID- 18826161
TI  - [Does the measured dose change when applying the new DIN 6800-2 (2008) versus the
      edition from 1997?].
AB  - New edition of DIN 6800-2 (1997) has been published in March 2008. The concept of
      absorbed dose to water has been retained unchanged. In many points modern data
      and approaches were adopted to international dosimetry protocols. For the first
      time values for the pertubation correction factors of plane parallel chambers are
      given in a dosimetry protocol. This enables the customer based on a Co-60
      calibration factor to measure absorbed dose to water without any cross
      calibration. In this paper new edition will be presented and compared with the
      old one. But main focus is set on the question, is there any deviation in the
      determination of dose when applying both protocols to same measured values. For
      photon beams and for in Germany common used types of ionization chambers the
      deviations are not larger than about 0.3% and for other types not larger than
      0.5%. However, in electron beams partly larger deviations up to 0.5% and for some
      types of ionization chambers even more than 1% may occur.

PMID- 18826162
TI  - Linear method of fluorescent source reconstruction in a diffusion medium.
AB  - A new method is described for obtaining a 2D reconstruction of a fluorescent
      source distribution inside a diffusion medium from planar measurements of the
      emission light at the surface after excitation by a plane wave. Point sources are
      implanted at known locations of a rectangular phantom. The forward model of the
      photon transport is based on the diffusion approximation of the radiative
      transport equation (RTE) for homogeneous media. This can be described by a
      hierarchical system of two time-independent RTE's, one for the excitation plane
      wave originating from the external light source to the medium and another one for
      the fluorescence emission originating from the fluorophore marker to the
      detector. A linear inverse source problem was solved for image reconstruction.
      The applicability of the theoretical method is demonstrated in some
      representative working examples. For an optimization of the problem we used least
      squares minimization technique.

PMID- 18826163
TI  - Broad beam attenuation measurements in lead in kilovoltage X-ray beams.
AB  - Broad beam attenuation is dependent on several parameters, such as the beam
      energy, thickness of attenuator, distance between the detector and attenuating
      material, atomic number of the attenuator, and the size and the volume of the
      ionization chamber. Lead is a common shielding material and hence the lead
      attenuation was studied in the context of the distance between detector and
      attenuating material and the chamber volume. Lead sheets of size 30 x 30 cm2 and
      high purity and precise thickness of 0.1 mm to 4.5 mm were used for the broad
      beam attenuation measurements of X-ray beams from a Philips Super 80CP unit with
      the range of 50 kVp-125 kVp. Six different chambers of 6 cm3, 15 cm3, 60 cm3, 150
      cm3, 180 cm3 and 600 cm3 volume from two manufacturers were used. The source to
      the attenuator distance was kept constant at 1 m and the distance between
      ionization chamber and attenuating material (Pb) was varied in the range of 0-20
      cm. The results show that the broad beam attenuation depends on the distance
      between chamber and attenuating material for each kV and ionization chamber
      volume. Shorter distances between chamber and attenuating material provide higher
      transmission. The attenuation differences were more pronounced at lower
      transmission values (< 10(-3)). The choice of the detector was shown not to be a
      critical factor except for the large volume of the 600 cm3 ionization chamber. In
      conclusions, broad beam attenuation measurements used for shielding calculation
      is relatively independent on the measuring devices except for a very large ion
      chamber. However, the distance between the attenuator and the detector is
      critical for the accuracy of attenuation measurements especially for smaller
      transmission values, which are most critical for public exposure.

PMID- 18826164
TI  - [Quantitative determination of cutoff perturbation factor pdelta in the DIN 6800
      2 (2008) by means of Monte Carlo simulations].
AB  - The new German DIN 6800-2 (2008) dosimetry protocol introduces a perturbation
      factor pdelta which accounts for the ionization chamber specific cutoff energy
      delta in the calculation of the Spencer-Attix stopping-power ratios. Quantitative
      values are not included in the protocol. In this study the perturbation factor
      was calculated for different types of ionization chambers using Monte Carlo
      simulations. For the choice of the cutoff energy the mean chord length of
      electrons in air filled cavities was calculated in a water phantom and for
      different beam qualities. The influence of different cutoff energies is not
      exceeding 0.1% for conventional ionization chambers.

PMID- 18826165
TI  - A social and historical perspective of the San Francisco Gay Men's Chorus.
AB  - This study sought to understand the various roles music played for gay men who
      were members of the San Francisco Gay Men's Chorus, the world's first gay men's
      chorus. Specifically, it answers the following questions: What is the demographic
      profile of the chorus members? How has the chorus shaped or reflected social
      issues; how has the chorus shaped or reflected political issues; how has the
      music evolved over time?; How was the chorus impacted by the HIV/AIDS epidemic?
      Historical information for this study was gathered through eight interviews of
      original and long-time choral members as well as the current artistic director.
      Interviews were conducted in San Francisco at the San Francisco Gay Men's Chorus
      office, and additional data were derived from programs of previous choral
      concerts, two questionnaires (Internalized Homophobia Scale and Gay Chorus
      Questionnaire), and observations of choral rehearsals and concerts. As a follow
      up to a previous study documenting the formation of the chorus in 1978-1982, this
      study historically documents the chorus's evolution from 1983 through 2003,
      emphasizing the chorus's impact on social and political issues, the musicality of
      the chorus, and the impact of HIV/AIDS on the chorus.

PMID- 18826166
TI  - Life-stories and storied lives: genre and reports of lived experience in gay
      personal literature.
AB  - Personal literature may be written either as a life story such as an
      autobiography or memoir or as an autobiographical novel. Using the three volumes
      comprising the memoir of author Paul Monette and the three volumes comprising the
      autobiographical fiction trilogy of journalist and novelist Edmund White, this
      article explores the goal of each author for selecting a particular genre in
      which to write about lived experience. Each author enjoyed an elite education and
      came to adulthood in postwar America in the decade prior to the gay rights era
      beginning in the 1970s, and each writer participated in the sociosexual culture
      emerging over the succeeding decade. Each writer became HIV+ in the 1980s
      (Monette died of complications attending AIDS in 1995), and each writer
      experienced the loss of his lover to AIDS. While Monette and White each
      experienced the anti-gay prejudice of postwar American society, Monette's youth
      was less troubled than that of White who grew up in a complex family with a
      distant yet harsh father toward whom he was also sexually attracted. While
      Monette's goal in writing a memoir was that the suffering of his generation of
      gay men should be remembered, White's goal was more personal, choosing
      autobiographical fiction in his effort to overcome his feelings of shame about
      being gay founded on his desire for his father.

PMID- 18826167
TI  - Age cohort differences in the developmental milestones of gay men.
AB  - As the social context in which gay men live changes due to greater visibility,
      greater acceptance, and easier access to gay subculture, gay males may self
      identify and take part in gay social activities at earlier ages than in the past.
      This study examined whether developmental milestones associated with sexual
      orientation for gay men have changed over the past several decades. A large and
      diverse sample of 2,402 gay men who responded to a 1994 survey published in a
      national magazine provided retrospective information on the age at which they
      reached individual psychological, social, and sexual behavior developmental
      milestones. We found evidence that individual psychological and sexual behavior
      milestones (e.g., awareness of attraction to males, having an orgasm with other
      male) are slowly moving toward earlier chronological ages (by 1 year of age every
      8-25 years, p < 0.05), whereas social milestones (e.g., coming out) are moving
      more rapidly in a similar direction (by 1 year of age every 2-5 years, p <
      0.001). The authors perform an innovative sensitivity test to demonstrate the
      persistence of the finding after correcting for the bias attributable to
      underrepresentation of those who have not yet self-identified as gay in such
      samples.

PMID- 18826168
TI  - Shall we marry? Legal marriage as a commitment event in same-sex relationships.
AB  - This study is a part of an exploratory study of 50 married and unmarried same-sex
      couples in Massachusetts conducted by the Wellesley Centers for Women following
      legalization of same-sex marriage in Massachusetts in 2004. This article examines
      whether and how legalization of same-sex marriage impacted same-sex partners'
      commitment to one another, presentation to others as a couple, and treatment as a
      couple by others. Roughly one-quarter of the couples studied chose not to mark
      their commitment with ceremonies of any kind, while nearly three-fourths of the
      couples had either commitment (non-legal) ceremonies, legal weddings, or both.
      While decisions to legally marry largely were based on gaining legal protections,
      unforeseen impacts on self and relationships with family, friends, and the larger
      society revealed multiple layers of meaning. Implications of the study for public
      policy and social change are discussed.

PMID- 18826169
TI  - Gay Abuse Screening Protocol (GASP): screening for abuse in gay male
      relationships.
AB  - Thirty-two male patients in gay relationships and eight family physicians were
      recruited from a family practice in order to determine comfort with an eight
      question Gay Abuse Screening Protocol (GASP). The GASP was administered during a
      typical clinical encounter. After the encounter, physicians and patients each
      completed a 5-point Likert Scale questionnaire to assess their comfort levels
      with each of the 8 GASP questions (Likert Scale: 1 = not at all comfortable to 5
      = very comfortable). The mean comfort score was high (Likert >4) for both
      patients (4.16 +/- 0.18) and physicians (4.71 +/- 0.18). However, mean comfort
      scores were significantly lower for abused patients (3.26 +/- 0.75) than
      nonabused patients (4.57 +/- 0.26). Patients were comfortable (Likert >3) with
      76.2% of GASP items while physicians were comfortable with all GASP items.

PMID- 18826170
TI  - Reduction of intimate partner violence in a gay couple following alcohol
      treatment.
AB  - Although intimate partner violence among heterosexual couples is a growing topic
      of investigation, there remains a critical deficiency in the amount of research
      on violence and relationship functioning in gay men. This article presents
      baseline and follow-up data on a case study examining the effects of partial
      hospital alcohol treatment on one gay couple. This information may be helpful in
      understanding the relationship between alcohol use, violence, and relationship
      functioning in this population. On the basis of past research involving
      heterosexual couples as participants, we predicted that subsequent to one patient
      receiving alcohol treatment: 1) alcohol consumption would be reduced; 2) there
      would be a reduction in the amount of psychological aggression between partners;
      3) there would be a reduction in the frequency of physically violent episodes;
      and 4) an overall improvement in relationship satisfaction would be evident. The
      couple was followed-up 6 and 12 months following the patient's alcohol treatment.
      The results indicate a decrease in alcohol use as well as reduced physical and
      psychological aggression, but no increase in relationship satisfaction. This case
      illustration may provide insight into the context surrounding intimate partner
      violence and relationship functioning in gay couples, with implications for
      further research and treatment.

PMID- 18826171
TI  - Predictors of sports motivation among gay and bisexual men.
AB  - Athletic activities are associated with reduced levels of stress and negative
      mood states among heterosexuals; thus, examining this association among
      gay/bisexual men is warranted. The current study examined the relationship
      between sports motivation and mood states, self-esteem, body esteem, life
      satisfaction, perceptions of masculinity/femininity, and parental encouragement
      for athletic endeavors among 195 gay/bisexual men. The results were mixed, but
      suggest that sports participation among gay/bisexual men may relate to a desire
      to express their masculinity and maintain a positive body image. Gay/bisexual men
      may be more likely to participate in sports if they receive positive
      reinforcement from others.

PMID- 18826172
TI  - [Etifoxine: a new look at the GABA receptor and anxiety].

PMID- 18826175
TI  - Examination of hypochlorous acid-induced damage to cytosine residues in a CpG
      dinucleotide in DNA.
AB  - Inflammation-mediated, neutrophil-derived hypochlorous acid can damage DNA and
      result in the chlorination damage products 5-chlorocytosine and 5-chlorouracil as
      well as the oxidation damage products 5-hydroxycytosine and 5-hydroxyuracil.
      While 5-chlorocytosine could potentially perturb epigenetic signals if formed at
      a CpG dinucleotide, the remaining products are miscoding and could result in
      transition mutations. In this article, we have investigated the reaction of
      hypochlorous acid with an oligonucleotide site-specifically enriched with 15N to
      probe the reactivity of cytosine at CpG. These experiments demonstrate directly
      the formation of 5-chlorocytosine at a CpG dinucleotide in duplex DNA. We observe
      that chlorination relative to oxidation damage is greater at CpG by a factor of
      approximately two, whereas similar amounts of 5-chlorocytosine and 5
      hydroxycytosine are formed at two non-CpG sites examined. The relative amounts of
      deamination of the cytosine to uracil derivatives are similar at CpG and non-CpG
      sites. Overall, we observe that the reactivity of cytosine at CpG and non-CpG
      sites toward hypochlorous acid induced damage is similar (5-chlorocytosine > 5
      hydroxycytosine > 5-hydroxyuracil > 5-chlorouracil), with a greater proportion of
      chlorination damage at CpG sites. These results are in accord with the potential
      of inflammation-mediated DNA damage to both induce transition mutations and to
      perturb epigenetic signals.

PMID- 18826176
TI  - Methylated bismuth, but not bismuth citrate or bismuth glutathione, induces cyto-
      and genotoxic effects in human cells in vitro.
AB  - Bismuth compounds are widely used in industrial processes and products. In
      medicine, bismuth salts have been applied in combination with antibiotics for the
      treatment of Helicobacter pylori infections, for the prevention of diarrhea, and
      in radioimmunotherapy. In the environment, bismuth ions can be biotransformed to
      the volatile bismuth compound trimethylbismuth (Me3Bi) by methanobacteria.
      Preliminary in-house studies have indicated that bismuth ions are methylated in
      the human colon by intestinal microflora following ingestion of bismuth
      containing salts. Information concerning cyto- and genotoxicity of these
      biomethylated products is limited. In the present study, we investigated the
      cellular uptake of an organic bismuth compound [monomethylbismuth(III),
      MeBi(III)] and two other bismuth compounds [bismuth citrate (Bi-Cit) and bismuth
      glutathione (Bi-GS)] in human hepatocytes, lymphocytes, and erythrocytes using
      ICP-MS. We also analyzed the cyto- and genotoxic effects of these compounds to
      investigate their toxic potential. Our results show that the methylbismuth
      compound was better taken up by the cells than Bi-Cit and Bi-GS. All
      intracellularly detected bismuth compounds were located in the cytosol of the
      cells. MeBi(III) was best taken up by erythrocytes (36%), followed by lymphocytes
      (17%) and hepatocytes (0.04%). Erythrocytes and hepatocytes were more susceptible
      to MeBi(III) exposure than lymphocytes. Cytotoxic effects of MeBi(III) were
      detectable in erythrocytes at concentrations >4 microM, in hepatocytes at >130
      microM, and in lymphocytes at >430 microM after 24 h of exposure. Cytotoxic
      effects for Bi-Cit and Bi-GS were much lower or not detectable in the used cell
      lines up to a tested concentration of 500 microM. Exposure of lymphocytes to
      MeBi(III) (250 microM for 1 h and 25 microM/50 microM for 24 h) resulted in
      significantly increased frequencies of chromosomal aberrations (CA) and sister
      chromatid exchanges (SCE), whereas Bi-Cit and Bi-GS induced neither CA nor SCE.
      Our study also showed an intracellular production of free radicals caused by
      MeBi(III) in hepatocytes but not in lymphocytes. These data suggest that
      biomethylation of bismuth ions by the intestinal microflora of the human colon
      leads to an increase in the toxicity of the primary bismuth salt.

PMID- 18826178
TI  - Multidimensional LC separations in shotgun proteomics.
AB  - Two modes of separation coupled with MS enable researchers to study complicated
      biological structures.

PMID- 18826179
TI  - Simulating the proton transfer in gramicidin A by a sequential dynamical Monte
      Carlo method.
AB  - The large interest in long-range proton transfer in biomolecules is triggered by
      its importance for many biochemical processes such as biological energy
      transduction and drug detoxification. Since long-range proton transfer occurs on
      a microsecond time scale, simulating this process on a molecular level is still a
      challenging task and not possible with standard simulation methods. In general,
      the dynamics of a reactive system can be described by a master equation. A
      natural way to describe long-range charge transfer in biomolecules is to
      decompose the process into elementary steps which are transitions between
      microstates. Each microstate has a defined protonation pattern. Although such a
      master equation can in principle be solved analytically, it is often too
      demanding to solve this equation because of the large number of microstates. In
      this paper, we describe a new method which solves the master equation by a
      sequential dynamical Monte Carlo algorithm. Starting from one microstate, the
      evolution of the system is simulated as a stochastic process. The energetic
      parameters required for these simulations are determined by continuum
      electrostatic calculations. We apply this method to simulate the proton transfer
      through gramicidin A, a transmembrane proton channel, in dependence on the
      applied membrane potential and the pH value of the solution. As elementary steps
      in our reaction, we consider proton uptake and release, proton transfer along a
      hydrogen bond, and rotations of water molecules that constitute a proton wire
      through the channel. A simulation of 8 mus length took about 5 min on an Intel
      Pentium 4 CPU with 3.2 GHz. We obtained good agreement with experimental data for
      the proton flux through gramicidin A over a wide range of pH values and membrane
      potentials. We find that proton desolvation as well as water rotations are
      equally important for the proton transfer through gramicidin A at physiological
      membrane potentials. Our method allows to simulate long-range charge transfer in
      biological systems at time scales, which are not accessible by other methods.

PMID- 18826180
TI  - Ab initio prediction of the emission color in phosphorescent iridium(III)
      complexes for OLEDs.
AB  - We performed fully first principles quantum mechanical calculations of the ground
      and excited state geometries and harmonic vibrational frequencies of two
      prototype cationic Ir(III) complexes showing high emission quantum efficiencies.
      Thanks to recent theoretical advances, we have been able for the first time to
      simulate their vibrationally resolved emission spectra. Our results, in good
      agreement with the experiment, allow us to calculate the CIE coordinates and
      therefore the emission color of this important class of emitters for OLEDs and
      LECs.

PMID- 18826181
TI  - Nanostructural organization and anion effects in the optical Kerr effect spectra
      of binary ionic liquid mixtures.
AB  - This article reports a study of the effect of anions on the optical Kerr effect
      (OKE) spectra of binary ionic liquid mixtures with one mixture comprising the 3
      methyl-1-pentylimidazolium ([C 5mim] (+)) cation and the anions PF 6 (-) and CF
      3CO 2 (-) (TFA (-)), and another mixture comprising the [C 5mim] (+) cation and
      the anions Br (-) and bis(trifluomethanesulfonyl)imide (NTf 2 (-)). The spectra
      were obtained by the use of optical heterodyne-detected Raman-induced Kerr Effect
      Spectroscopy at 295 K. The OKE spectra of the mixtures are compared with the
      calculated mole-fraction weighted sum of the normalized OKE spectra of the neat
      liquids. The OKE spectra are nearly additive for [C 5mim]Br/[C 5mim][NTf 2]
      mixtures, but nonadditive for [C 5mim][PF 6]/[C 5mim][TFA] mixtures. In the case
      of the equimolar [C 5mim][PF 6]/[C 5mim][TFA] mixture, the nonadditivity is such
      that the experimental OKE spectrum is narrower than the calculated OKE spectrum.
      The additivity or nonadditivity of OKE spectra for IL mixtures can be explained
      by assuming ionic liquids are nanostructurally organized into nonpolar regions
      and ionic networks. The ionic networks in mixtures will be characterized by
      "random co-networks" for anions that are nearly the same in size (PF 6 (-) and
      TFA (-)) and by "block co-networks" for anions that differ greatly in size (Br (
      ) and NTf 2 (-)).

PMID- 18826182
TI  - Exploring the effects of intramolecular vibrational energy redistribution on the
      operation of the proton wire in green fluorescent protein.
AB  - The operation of the proton wire in Green Fluorescent Protein has been simulated
      by quantum dynamics and considering the coupling to the protein environment by
      means of a bath of harmonic oscillators. The simulation consists of 36 explicit
      and fully quantum degrees of freedom: 6 degrees of freedom represent the
      configuration of the proton wire, which are coupled to 30 bath coordinates.
      Regimes of weak and strong coupling have been studied. It is found that presence
      of the bath induces a fast energy transfer from the proton wire to the bath, with
      characteristic times under 400 fs. This internal vibrational redistribution
      happens at the expense of the potential energy content of the proton wire,
      deformed through the interaction to the bath from its uncoupled state. Strong
      coupling induces a slowing-down of the operation of the wire because it hinders
      to some extent the approaching of donor and acceptor atoms to distances in which
      proton transfer can occur. Internal vibrational energy redistribution affects the
      dynamics, but from our simulations we conclude that it cannot be the only cause
      responsible for the experimentally reported fluorescence rise times.

PMID- 18826183
TI  - Thermal properties and mixing state of diol-water mixtures studied by
      calorimetry, large-angle X-ray scattering, and NMR relaxation.
AB  - Differential scanning calorimetry (DSC) has been performed on aqueous mixtures of
      three diols, which involve a linear carbon chain, HO-(CH 2) n -OH ( n = 3, 4, and
      5), over the whole mole fraction range of diols. The DSC results have shown the
      alkyl chain parity for the freezing process of the aqueous mixtures: aqueous
      mixtures of 1,3-propanediol (PrD) and 1,5-pentanediol (PeD) are kept in the
      supercooled state or vitrified over a wide mole fraction range, while those of
      1,4-butanediol (BuD) are easily crystallized. The structure of PrD-water mixtures
      has been elucidated by using the large-angle X-ray scattering (LAXS) technique.
      It has been suggested that the structural change of PrD-water mixtures occurs at
      PrD mole fractions of x PrD = 0.4 and 0.8: in the range of x PrD < or = 0.4 where
      the tetrahedral-like structure of water predominates, in the range of 0.4 < x PrD
      < 0.8 where both PrD and water structures coexist, and in the range of x PrD > or
      = 0.8 where the inherent structure of PrD is mainly formed. (17)O and (1)H NMR
      relaxation measurements have been made on aqueous mixtures of ethylene glycol
      (EG, n = 2), PrD, and BuD to clarify the dynamics of H 2 (17)O and diol
      molecules. The (17)O NMR relaxation rates have suggested that the rotational
      motion of water molecules is gradually retarded in the diol-water mixtures with
      increasing diol content and that the restriction of the motion is more remarkable
      in the order of EG < PrD < BuD. On the basis of all the results, together with
      comparison with those of methanol-water, ethanol-water, and 1-propanol-water
      mixtures previously reported, the mixing state of diol-water mixtures has been
      discussed at the molecular level.

PMID- 18826184
TI  - Supercoiling and local denaturation of plasmids with a minimalist DNA model.
AB  - We report molecular dynamics simulations of DNA nanocircles and submicrometer
      sized plasmids with torsional stress. The multiple microseconds time scale is
      reached thanks to a new one-bead-per-nucleotide coarse-grained model that
      combines structural accuracy and predictive power, achieved by means of the
      accurate choice of the force field terms and their unbiased statistically based
      parametrization. The model is validated with experimental structural data and
      available all-atom simulations of DNA nanocircles. Besides reproducing the
      nanocircles' structures and behavior on the short time scale, our model is
      capable of exploring three orders of magnitude further in time and to sample more
      efficiently the configuration space, unraveling novel behaviors. We explored the
      microsecond dynamics of entire small plasmids and observed supercoiling and
      compaction in the overtwisted case. The stability of overtwisted nanocircles and
      plasmids is predicted up to macroscopic time scales. Conversely, in the
      undertwisted case, at physiological values of the superhelical density, after a
      metastable phase of supercoiling-compaction, we observe the formation and the
      complex dynamics of denaturation bubbles over a multiple microseconds time scale.
      Our results indicate that the torsional stress is involved in a delicate balance
      with the temperature to determine the denaturation equilibrium and regulate the
      transcription process.

PMID- 18826185
TI  - Free solution electrophoresis of homopolyelectrolytes.
AB  - We investigate the behavior of single polyelectrolytes in multivalent salt
      solutions under the action of electric fields through computer simulations. The
      chain is unfolded in a strong electric field and aligned parallel to the field
      direction, and the chain size shows a sigmoidal transition. The unfolding
      electric field E* depends on the salt concentration and scales as V (-1/2) with V
      being the ellipsoidal volume occupied by the chain. The magnitude of the
      electrophoretic mobility of chain drastically increases during the unfolding. The
      fact that E* depends on the chain length provides a plausible mechanism to
      separate long charged homopolymers by size in free solution electrophoresis via
      the unfolding transition of globule polyelectrolytes condensed by multivalent
      salt.

PMID- 18826186
TI  - A structural transition in duplex DNA induced by ethylene glycol.
AB  - The twist energy parameter ( E T) that governs the supercoiling free energy, and
      the linking difference (Delta l) are measured for p30delta DNA in solutions
      containing 0-40 w/v % ethylene glycol (EG). A plot of E T vs -ln a w, where a w
      is the water activity, displays the full (reverse) sigmoidal profile of a
      discrete structural transition. A general theory for the effect of added osmolyte
      on a cooperative structural transition between two duplex states, 1 right arrow
      over left arrow 2, is formulated in terms of parameters applicable to individual
      base-pair subunits. The resulting fraction of base pairs in the 2-state ( f 2
      (0)) is incorporated into expressions for the effective torsion and bending
      elastic constants, the effective twist energy parameter ( E T (eff)), and the
      change in intrinsic twist (delta l 0). Fitting the expression for E T (eff) to
      the measured E T values yields reasonably unambiguous estimates of E T 1 and E T
      2 , the midpoint value (ln a w) 1/2, and the midpoint slope ( partial
      differential E T/ partial differential ln a w) 1/2, but does not yield
      unambiguous estimates of the equilibrium constant ( K 0), the difference in DNA
      water preferential interaction coefficient (DeltaGamma), or the inverse
      cooperativity parameter ( J). Fitting a noncooperative model (assumed J = 1.0) to
      the data yields K 0 = 0.067 and DeltaGamma = -30.0 per base pair (bp).
      Essentially equivalent fits are provided by models with a wide range of
      correlated J, DeltaGamma, and K 0 values. Other results favor DeltaGamma in the
      range -1.0 to 0, which then requires K 0 > or = 0.914, and a cooperativity
      parameter, 1/ J > or = 30.0 bp. The measured delta l 0 and circular dichroism
      (CD) at 272 nm are found to be compatible with curves predicted using the same f
      2 (0) values that best-fit the E T data. At least 7-10% of the base pairs are
      inferred to exist in the 2-state in 0.1 M NaCl in the complete absence of added
      osmolyte. Compared with the 1-state, the 2-state has a approximately 2.0- to 2.1
      fold greater torsion elastic constant, a approximately 0.70-fold smaller bending
      elastic constant, a approximately 0.91-fold smaller E T value, a approximately
      0.2% lower intrinsic twist, a somewhat lower CD near both 272 and 245 nm, and
      less water and/or more EG in its neighborhood. However, the relative change in
      preferential interaction coefficient associated with the transition is likely
      rather slight.

PMID- 18826187
TI  - Investigating the polymorphism in PR179: a combined crystal structure prediction
      and metadynamics study.
AB  - The polymorphism of an industrial important pigment (PR179) was studied with a
      combination of standard crystal structure prediction and metadynamics. The former
      provided a starting set of candidate polymorphs whose structural and thermal
      stability were then probed by metadynamics. Moreover, metadynamics allowed for
      exploring the free energy surface to look for other possible polymorphs that were
      not included in the original set. Our calculations indicate that two structures
      have a high structural stability and are therefore good candidates to be found in
      experiments. The lower energy phase of the two indeed corresponds to the known
      polymorph, and we suggest that the other might be a metastable polymorph not yet
      experimentally discovered.

PMID- 18826188
TI  - Anatomy of an energy transfer event in a liquid: the high-energy rotational
      relaxation of OH in solution.
AB  - The photochemical generation of highly rotationally excited diatomics affords us
      an intriguing way to study energy relaxation processes in solution. Because
      excited products involve only a single intramolecular degree of freedom and
      because their relaxations can lie well outside of the linear-response regime, it
      may be possible to infer detailed molecular mechanisms for these processes just
      from transient absorption measurements. In this paper we describe a theoretical
      study of the rotational relaxation of a new candidate for such measurements, OH
      radicals. Much as we saw in our previous studies of rotationally hot CN radicals,
      molecular dynamics simulations of OH relaxation predict that the rotational
      motion should trigger a structural change in the surrounding solvent, decreasing
      the rotational friction and allowing the OH to rotate coherently for a dozen
      rotational periods. The mass distribution in OH, however, gives it a much faster
      rotational period and significantly different kinematics. These differences end
      up making it possible to identify the separate molecular events taking place at
      the onset of the relaxation (an unusual occurrence for a liquid-state process)
      and to weigh in on what collisions are really like in a liquid.

PMID- 18826189
TI  - A theoretical study on the detection of proton transfer pathways in some mutants
      of human carbonic anhydrase II.
AB  - Structural and kinetic studies of mutants can give much insight into the function
      of an enzyme. We report the detection of possible proton transfer pathways into
      the active site of a number of mutants of the enzyme human carbonic anhydrase II
      (HCA II). Using a recently developed method of path search in the protein
      conformational space, we identify hydrogen-bonded networks (or proton paths) that
      can dynamically connect the protein surface to the active site through
      fluctuations in protein structure and hydration. The feasibility of establishing
      such dynamical connectivities is assessed by computing the change in free energy
      of conformational fluctuations and compared to those identified earlier in the
      wild type enzyme. It is found that the point mutation facilitates or suppresses
      one or more of the alternative pathways. Our results allow the use of a generic
      set of pathways to correlate qualitatively the residual activity in the mutants
      to the molecular mechanism of proton transfer in the absence of His at position
      64. We also demonstrate how the detected pathways may be used to compare the
      efficiencies of the mutants His-64-Ala/Asn-62-His and His-64-Ala/Asn-67-His using
      the empirical valence bond theory.

PMID- 18826190
TI  - Heterogeneous electron transfer kinetics at the ionic liquid/metal interface
      studied using cyclic voltammetry and scanning electrochemical microscopy.
AB  - The electrochemical behavior of a redox-active, ferrocene-modified ionic liquid
      (1-ferrocenylmethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide) in
      acetonitrile and in an ionic liquid electrolyte (1-ethyl-3-methylimidazolium
      bis(trifluoromethylsulfonyl)imide) is reported. Reversible electrochemical
      behavior was observed in each electrolyte with responses typical of those for
      unmodified ferrocene observed in each medium. In the ionic liquid electrolyte,
      the diffusion coefficient of the redox-active ionic liquid increased by a factor
      of 5 upon increasing the temperature from 27 to 90 degrees C. The kinetics of
      electron transfer across the ionic liquid/electrode interface were studied using
      cyclic voltammetry, and the standard heterogeneous electron transfer rate
      constant, k (0) was determined to be 4.25 x 10 (-3) cm s (-1). Scanning
      electrochemical microscopy was then also used to probe the heterogeneous kinetics
      at the interface between the ionic liquid and the solid electrode and
      conventional kinetic SECM theory was used to determine k (0). The k (0) value
      obtained using SECM was higher than that determined using cyclic voltammetry.
      These results indicate that SECM is a very useful technique for studying electron
      transfer dynamics in ionic liquids.

PMID- 18826191
TI  - Kinetic modeling of charge-transfer quenching in the CP29 minor complex.
AB  - We performed transient absorption (TA) measurements on CP29 minor light
      harvesting complexes that were reconstituted in vitro with either violaxanthin
      (Vio) or zeaxanthin (Zea) and demonstrate that the Zea-bound CP29 complexes
      exhibit charge-transfer (CT) quenching that has been correlated with the energy
      dependent quenching (qE) in higher plants. Simulations of the difference TA
      kinetics reveal two-phase kinetics for intracomplex energy transfer to the CT
      quenching site in CP29 complexes, with a fast <500 fs component and a
      approximately 6 ps component. Specific chlorophyll sites within CP29 are
      identified as likely locations for CT quenching. We also construct a kinetic
      model for CT quenching during qE in an intact system that incorporates CP29 as a
      CT trap and show that the model is consistent with previous in vivo measurements
      on spinach thylakoid membranes. Finally, we compare simulations of CT quenching
      in thylakoids with those of the individual CP29 complexes and propose that CP29
      rather than LHCII is a site of CT quenching.

PMID- 18826192
TI  - Development of a finite-temperature density functional approach to
      electrochemical reactions.
AB  - We present a computational method to calculate the electronic states of a
      molecule in an electrochemical environment. The method is based on our recently
      developed finite-temperature density functional theory approach to calculate the
      electronic structures at a constant chemical potential. A solvent effect is
      treated at the level of the extended self-consistent reaction field model, which
      allows considering a nonequilibrium solvation effect. An exchange-correlation
      functional with a long-range correction is employed in this calculation, because
      the functional is adjusted so that the derivative discontinuity of energy with
      respect to a number of electrons could be satisfied. It has been found that the
      derivative discontinuity condition plays a crucial role in an electrochemical
      system. The computational results are presented for a reaction of NO(+) + e(-)
      <==> NO in chemical equilibrium. Owing to the improvement in the solvation effect
      and the exchange-correlation functional, the calculated activation free energy is
      in good agreement with experimental results.

PMID- 18826193
TI  - Desorption of polycyclic aromatic hydrocarbons from soot surface: pyrene and
      fluoranthene.
AB  - The kinetics of thermal desorption of two four-ring polycyclic aromatic
      hydrocarbons, fluoranthene, and pyrene from well-characterized laboratory
      generated kerosene soot surface was studied over the temperature range 260-320 K
      in a low-pressure flow reactor combined with an electron-impact mass
      spectrometer. Two methods were used to measure the desorption rate constants:
      monitoring of the surface-bound fluoranthene and pyrene decays due to desorption
      using off-line HPLC measurements of their concentrations in soot samples, and
      monitoring of the desorbed molecules in the gas phase using in situ mass
      spectrometric detection. Results obtained with the two methods were in good
      agreement and yielded the following Arrhenius expressions for the desorption rate
      constants: k(des) (fluoranthene) = 4 x 10(14) exp[-(93900 +/- 1700)/RT] and
      k(des) (pyrene) = 6 x 10(14) exp[-(95200 +/- 1800)/RT] (k(des) are in units of s(
      1), and activation energies are in J mol(-1)). In addition, the combined uptake
      coefficient of fluoranthene and pyrene on soot (calculated using specific surface
      area) was estimated to be near 5 x 10(-3) at T = 310 K.

PMID- 18826194
TI  - High-resolution infrared spectroscopy of trans- and cis-H(18)ON(18)O: equilibrium
      structures of the nitrous acid isomers.
AB  - In this paper, we present the first high-resolution spectra and analysis of the
      nu 4 fundamental bands of fully (18)O-substituted nitrous acid, trans- and cis
      H(18)ON(18)O. These bands are not perturbed by neighboring vibrational levels and
      were used to determine for the first time accurate rotational and centrifugal
      distortion constants of the ground and nu 4 = 1 states of trans- and cis
      H(18)ON(18)O. The ground-state rotational constants were then used, together with
      the rotational constants of other HONO isotopic species and with rotation
      vibration parameters from ab initio calculations, to determine accurate semi
      experimental equilibrium structures of trans- and cis-HONO. Our study confirms
      the results of a recent work by Demaison et al. (J. Phys. Chem. A 2006, 110,
      13609-13617) concerning the structure of trans-HONO, whereas the new structure of
      cis-HONO obtained in this paper is a significant improvement compared with the
      previous work of Cox et al. (J. Mol. Struct. 1994, 320, 91-106). The recommended
      parameters for the equilibrium structure of cis-HONO are r(e)(ON) = 1.1816(10) A,
      r(e)(N-O) = 1.3887(10) A, r(e)(O-H) = 0.9744(7) A, angle(e)(ONO) = 113.18(1)
      degrees, and angle(e)(HON) = 104.67(4) degrees.

PMID- 18826195
TI  - An oligomer study on small band gap polymers.
AB  - Small band gap polymers may increase the energy conversion efficiency of polymer
      solar cells by increased absorption of sunlight. Here we present a combined
      experimental and theoretical study on the optical and electrochemical properties
      of a series of well-defined, lengthy, small band gap oligo(5,7-bis(thiophen-2
      yl)thieno[3,4-b]pyrazine)s ( E g = 1.50 eV) having alternating donor and acceptor
      units. The optical absorptions of the ground state, triplet excited state,
      radical cation, and dication are identified and found to shift to lower energy
      with increasing chain length. The reduction of the band gap in these alternating
      small band gap oligomers mainly results from an increase of the highest occupied
      molecular orbital (HOMO) level. The S 1-T 1 singlet-triplet splitting is reduced
      from approximately 0.9 eV from the trimeric monomer to -0.5 eV for the pentamer.
      This significant exchange energy is consistent with the fact that both the HOMO
      and the lowest unoccupied molecular orbital (LUMO) remain distributed over
      virtually all units, rather than being localized on the D and A units.

PMID- 18826196
TI  - Homobenzene: homoaromaticity and homoantiaromaticity in cycloheptatrienes.
AB  - Cycloheptatriene (C(s)) is firmly established to be a neutral homoaromatic
      molecule based on detailed analyses of geometric, energetic, and magnetic
      criteria. Substituents at the 7 (methylene) position, ranging from the
      electropositive BH2 to the electronegative F, favor the equatorial conformation
      but influence the aromaticity only to a small extent. By the same criteria, the
      planar transition state (C(2v)) for cycloheptatriene ring inversion is clearly
      antiaromatic. This is attributed to the involvement of the pseudo-2pi-electrons
      of the CH2 group with the 6pi-electrons of the ring to give an 8pi-electron
      system. Similarly, the participation of the CH2 groups into C(2v) cyclopentadiene
      and cyclononatetraene lead to significant 4n + 2 pi electron aromaticity. The
      cyclization of cycloheptatriene to norcaradiene proceeds via a highly aromatic
      transition structure, but norcaradiene itself is less aromatic than
      cycloheptatriene. An annelated cyclopropane ring does not function as effectively
      as a double bond in promoting cyclic electron delocalization.

PMID- 18826197
TI  - Organic carbonates: experiment and ab initio calculations for prediction of
      thermochemical properties.
AB  - This work has been undertaken in order to obtain data on thermodynamic properties
      of organic carbonates and to revise the group-additivity values necessary for
      predicting their standard enthalpies of formation and enthalpies of vaporization.
      The standard molar enthalpies of formation of dibenzyl carbonate, tert-butyl
      phenyl carbonate, and diphenyl carbonate were measured using combustion
      calorimetry. Molar enthalpies of vaporization of these compounds were obtained
      from the temperature dependence of the vapor pressure measured by the
      transpiration method. Molar enthalpy of sublimation of diphenyl carbonate was
      measured in the same way. Ab initio calculations of molar enthalpies of formation
      of organic carbonates have been performed using the G3MP2 method, and results are
      in excellent agreement with the available experiment. Then the group-contribution
      method has been developed to predict values of the enthalpies of formation and
      enthalpies of vaporization of organic carbonates.

PMID- 18826198
TI  - High-pressure effects in pyrene crystals: vibrational spectroscopy.
AB  - The response of pyrene crystals to high pressure was examined using Raman and
      FTIR spectroscopies. Raman spectra of external and internal modes were measured
      up to 11 GPa. Changes in the external modes were observed at approximately 0.3
      GPa, indicating the onset of a phase transition. We demonstrated that at this
      pressure pyrene I (P2(1)/a, 4 mol/unit cell) transforms to pyrene III (P2(1)/a, 2
      mol/unit cell). Further increase of pressure produced a gradual broadening of the
      internal modes and an increase of fluorescence background, indicating the
      formation of another phase above 2.0 GPa. Irreversible chemical changes were
      observed upon gradual compression to 40 GPa. FTIR spectroscopy of the recovered
      product indicated a transformation of pyrene into an amorphous hydrogenated
      carbon (a-C:H) structure.

PMID- 18826199
TI  - Unraveling complex three-body photodissociation dynamics of dimethyl sulfoxide: a
      femtosecond time-resolved spectroscopic study.
AB  - Photodissociation of dimethyl sulfoxide at 200 nm has been studied using
      femtosecond time-resolved spectroscopy. The temporal evolutions of the initial
      state, intermediates, and products (CH3 and SO) were measured by means of fs pump
      probe mass-selected multiphoton ionization and laser-induced fluorescence.
      Femtosecond time-resolved photofragment translational spectroscopy was also
      employed to measure the CH3 product kinetic energy distributions as a function of
      reaction time. The ionization experiments revealed that there are at least three
      major CH3 product components, whereas the fluorescence experiments indicated that
      two SO product components are present. The combination of experimental and
      theoretical results suggested a complex multichannel mechanism involving both
      concerted and stepwise three-body dissociation pathways.

PMID- 18826200
TI  - Transition state barriers in multidimensional Marcus theory.
AB  - Multidimensional Marcus theory is the extension of traditional Marcus theory to
      systems in which multiple particles are transferred. Rather than the intersecting
      parabolas of Marcus theory, multidimensional Marcus theory involves the
      intersection of paraboloids. In this paper, we examine the conditions under which
      a full multidimensional treatment of these paraboloids is necessary and when it
      is possible to use a simpler one-dimensional formalism. In particular, we examine
      transition state barrier energies, which are essential parameters in many
      reaction rate equations, and which depend on the formalism used. We find, based
      on both analytic calculations and numerical simulation, that the reduced one
      dimensional treatment yields excellent agreement with the exact, multidimensional
      results over a wide variety of conditions for one particular choice of the single
      collective reaction coordinate. We also outline a procedure for calculating
      accurate multidimensional transition state barrier energies and apply it to a two
      dimensional model of proton-coupled electron transfer.

PMID- 18826201
TI  - Boiling points of halogenated ethanes: an explanatory model implicating weak
      intermolecular hydrogen-halogen bonding.
AB  - This study explores via structural clues the influence of weak intermolecular
      hydrogen-halogen bonds on the boiling point of halogenated ethanes. The plot of
      boiling points of 86 halogenated ethanes versus the molar refraction (linked to
      polarizability) reveals a series of straight lines, each corresponding to one of
      nine possible arrangements of hydrogen and halogen atoms on the two-carbon
      skeleton. A multiple linear regression model of the boiling points could be
      designed based on molar refraction and subgroup structure as independent
      variables (R(2) = 0.995, standard error of boiling point 4.2 degrees C). The
      model is discussed in view of the fact that molar refraction can account for
      approximately 83.0% of the observed variation in boiling point, while 16.5% could
      be ascribed to weak C-X...H-C intermolecular interactions. The difference in the
      observed boiling point of molecules having similar molar refraction values but
      differing in hydrogen-halogen intermolecular bonds can reach as much as 90
      degrees C.

PMID- 18826202
TI  - Synthesis and evaluation of novel boron-containing complexes of potential use for
      the selective treatment of malignant melanoma.
AB  - Boron-containing complexes that have the potential to irreversibly accumulate in
      melanoma cells have been prepared by reaction of amino acids with 9-methoxy-9
      borabicyclo[3.3.1]nonane. The ability of each complex to act as a substrate for
      tyrosinase has been probed by oximetry. Increased uptake of the lead candidate in
      a tyrosinase-rich cell line, compared with a tyrosinase-absent cell line, is
      reported, with results correlating well with that for a drug currently approved
      for BNCT.

PMID- 18826203
TI  - Intracellular trapping of cycloSal-pronucleotides: modification of prodrugs with
      amino acid esters.
AB  - A new class of d4TMP- cycloSal-pronucleotides bearing enzymatically cleavable
      amino acid esters is reported. These compounds are designed to trap the
      pronucleotide inside the cell by a fast conversion of a nonpolar ester group into
      a charged carboxylate. This should prevent efficient diffusion equilibrium across
      the cell membrane to the extracellular environment, leading to an intracellular
      accumulation of the compounds. This initial conversion is followed by a slow
      release of the nucleoside monophosphate (i.e., d4TMP). The concept is proven by
      hydrolysis studies in phosphate buffer, cell extracts, and human serum. These
      investigations revealed a high sensitivity of some amino acid ester modifications
      to conversion by cellular extracts, resulting in the fast release of a charged
      intermediate, whereas no cleavage of the modification is found in phosphate
      buffer. In addition, antiviral activities against HIV are presented.

PMID- 18826204
TI  - Discovery of 3-{5-[(6-amino-1H-pyrazolo[3,4-b]pyridine-3-yl)methoxy]-2
      chlorophenoxy}-5-chlorobenzonitrile (MK-4965): a potent, orally bioavailable HIV
      1 non-nucleoside reverse transcriptase inhibitor with improved potency against
      key mutant viruses.
AB  - Non-nucleoside reverse transcriptase inhibitors (NNRTIs) have been shown to be a
      key component of highly active antiretroviral therapy (HAART). The use of NNRTIs
      has become part of standard combination antiviral therapies producing clinical
      outcomes with efficacy comparable to other antiviral regimens. There is, however,
      a critical issue with the emergence of clinical resistance, and a need has arisen
      for novel NNRTIs with a broad spectrum of activity against key HIV-1 RT
      mutations. Using a combination of traditional medicinal chemistry/SAR analyses,
      crystallography, and molecular modeling, we have designed and synthesized a
      series of novel, highly potent NNRTIs that possess broad spectrum antiviral
      activity and good pharmacokinetic profiles. Further refinement of key compounds
      in this series to optimize physical properties and pharmacokinetics has resulted
      in the identification of 8e (MK-4965), which has high levels of potency against
      wild-type and key mutant viruses, excellent oral bioavailability and overall
      pharmacokinetics, and a clean ancillary profile.

PMID- 18826205
TI  - Design, synthesis, and biological evaluation of novel constrained meta
      substituted phenyl propanoic acids as peroxisome proliferator-activated receptor
      alpha and gamma dual agonists.
AB  - In an effort to develop dual PPARalpha/gamma activators with improved therapeutic
      efficacy, a series of diaryl alpha-ethoxy propanoic acid compounds comprising two
      aryl groups linked by rigid oxime ether or isoxazoline ring were designed and
      synthesized and their biological activities were examined. Most of the compounds
      possessing an oxime ether linker were more potent PPARgamma activators than the
      lead PPARalpha/gamma dual agonist, tesaglitazar in vitro. Compound 18, one of the
      derivatives with an oxime ether linker, was found to selectively transactivate
      PPARgamma (EC 50 = 0.028 microM) over PPARalpha (EC 50 = 7.22 microM) in vitro
      and lower blood glucose in db/ db mice more than muraglitazar after oral
      treatment for 11 days.

PMID- 18826206
TI  - Differences between high- and low-affinity complexes of enzymes and nonenzymes.
AB  - Physical differences in small molecule binding between enzymes and nonenzymes
      were found through mining the protein-ligand database, Binding MOAD (Mother of
      All Databases). The data suggest that divergent approaches may be more productive
      for improving the affinity of ligands for the two classes of proteins. High
      affinity ligands of enzymes are much larger than those with low affinity,
      indicating that the addition of complementary functional groups is likely to
      improve the affinity of an enzyme inhibitor. However, this process may not be as
      fruitful for ligands of nonenzymes. High- and low-affinity ligands of nonenzymes
      are nearly the same size, so modest modifications and isosteric replacement might
      be most productive. The inherent differences between enzymes and nonenzymes have
      significant ramifications for scoring functions and structure-based drug design.
      In particular, nonenzymes were found to have greater ligand efficiencies than
      enzymes. Ligand efficiencies are often used to indicate druggability of a target,
      and this finding supports the feasibility of nonenzymes as drug targets. The
      differences in ligand efficiencies do not appear to come from the ligands;
      instead, the pockets yield different amino acid compositions despite very similar
      distributions of amino acids in the overall protein sequences.

PMID- 18826207
TI  - Targeting the conformational transitions of MDM2 and MDMX: insights into
      dissimilarities and similarities of p53 recognition.
AB  - MDM2 and MDMX are oncogenic homologue proteins that regulate the activity and
      stability of p53, a tumor suppressor protein involved in more than 50% of human
      cancers. While the large body of experiments so far accumulated has validated
      MDM2 as a therapeutically important target for the development of anticancer
      drugs, it is only recently that MDMX has also become an attractive target for the
      treatment of tumor cells expressing wild type p53. The availability of structural
      information of the N-terminal domain of MDM2 in complex with p53-derived peptides
      and inhibitors, and the very recent disclosure of the crystal structure of the N
      terminal domain of MDMX bound to a p53 peptide, offer an unprecedented
      opportunity to provide insight into the molecular basis of p53 recognition and
      the identification of discriminating features affecting the binding of the tumor
      suppressor protein at MDM2 and MDMX. By using coarse graining simulations, in
      this study we report the exploration of the conformational transitions featured
      in the pathway leading from the apo-MDM2 and apo-MDMX states to the p53-bound
      MDM2 and p53-bound MDMX states, respectively. The results have enabled us to
      identify a pool of diverse conformational states of the oncogenic proteins that
      affect the binding of p53 and the presence of conserved and non-conserved
      interactions along the conformational transition pathway that may be exploited in
      the design of selective and dual modulators of MDM2 and MDMX activity.

PMID- 18826208
TI  - Robust cross-validation of linear regression QSAR models.
AB  - A quantitative structure-activity relationship (QSAR) model is typically
      developed to predict the biochemical activity of untested compounds from the
      compounds' molecular structures. "The gold standard" of model validation is the
      blindfold prediction when the model's predictive power is assessed from how well
      the model predicts the activity values of compounds that were not considered in
      any way during the model development/calibration. However, during the development
      of a QSAR model, it is necessary to obtain some indication of the model's
      predictive power. This is often done by some form of cross-validation (CV). In
      this study, the concepts of the predictive power and fitting ability of a
      multiple linear regression (MLR) QSAR model were examined in the CV context
      allowing for the presence of outliers. Commonly used predictive power and fitting
      ability statistics were assessed via Monte Carlo cross-validation when applied to
      percent human intestinal absorption, blood-brain partition coefficient, and
      toxicity values of saxitoxin QSAR data sets, as well as three known benchmark
      data sets with known outlier contamination. It was found that (1) a robust
      version of MLR should always be preferred over the ordinary-least-squares MLR,
      regardless of the degree of outlier contamination and that (2) the model's
      predictive power should only be assessed via robust statistics. The Matlab and
      java source code used in this study is freely available from the QSAR-BENCH
      section of www.dmitrykonovalov.org for academic use. The Web site also contains
      the java-based QSAR-BENCH program, which could be run online via java's Web Start
      technology (supporting Windows, Mac OSX, Linux/Unix) to reproduce most of the
      reported results or apply the reported procedures to other data sets.

PMID- 18826209
TI  - pKa prediction of monoprotic small molecules the SMARTS way.
AB  - Realizing favorable absorption, distribution, metabolism, elimination, and
      toxicity profiles is a necessity due to the high attrition rate of lead compounds
      in drug development today. The ability to accurately predict bioavailability can
      help save time and money during the screening and optimization processes. As
      several robust programs already exist for predicting logP, we have turned our
      attention to the fast and robust prediction of pK(a) for small molecules. Using
      curated data from the Beilstein Database and Lange's Handbook of Chemistry, we
      have created a decision tree based on a novel set of SMARTS strings that can
      accurately predict the pK(a) for monoprotic compounds with R(2) of 0.94 and root
      mean squared error of 0.68. Leave-some-out (10%) cross-validation achieved Q(2)
      of 0.91 and root mean squared error of 0.80.

PMID- 18826210
TI  - Trianionic organoborate triangles.
AB  - The rigid, angular ligand 3,3,3',3'-tetramethyl-1,1'spirobisindane-5,5',6,6'
      tetrol, LH4, in the form of its tetra-anion, L(4-), affords crystalline compounds
      containing the triangular macrocyclic boron derivative [B3L3](3-) with the
      counter cations, triethylammonium, imidazolium, tetraethylammonium, and
      protonated dabco (dabco = 1,4-diazabicyclo[2,2,2]octane). Within a triangular
      unit all three chiral L(4-) ligands have the same hand although the crystal does
      contain a racemic mixture of macrocycles. In all four compounds, one out of the
      three counter-cations per macrocycle is bound inside the macrocycle.

PMID- 18826211
TI  - A new class of sulfido/oxo(dithiolene)-molybdenum(IV) complexes derived from
      sulfido/oxo-bis(tetrasulfido)molybdenum(IV) anions.
AB  - Mono(dithiolene)sulfidomolybdenum(IV) complexes, [MoS(S4)(bdt)](2-) (2) and
      [MoS(S4)(bdtCl2)](2-) (3) (1,2-benzenedithiolate = bdt, 3,6-dichloro-1,2
      benzenedithiolate = bdtCl2), were prepared by the substitution reaction of a
      tetrasulfido ligand in known [MoS(S4)2](2-) (1) with the corresponding dithiol.
      Complexes 2 and 3 were irreversibly oxidized to give bis(mu-sulfido)
      dimolybdenum(V) species, {[MoS(bdt)]2(mu-S)2}(2-) (4) and {[MoS(bdtCl2)]2(mu
      S)2}(2-) (5), in aerobic acetonitrile. Mono(dithiolene)oxomolybdenum(IV)
      complexes, [MoO(S4)(bdt)](2-) (7) and [MoO(S4)(bdtCl2)](2-) (8), that are oxo
      derivatives of 2 and 3 were also synthesized from a known [MoO(S4)2](2-) (6) of
      an oxo derivative of 1 and the corresponding dithiol. Further, the electrophilic
      addition of dimethyl acetylenedicarboxylate to 7 gave [MoO(bdt)(S2C2(COOMe)2)](2
      ) (9), and ligand substitution of the tetrasulfido group of 7 with bdt and bdtCl2
      yielded [MoO(bdt)2](2-) ( 10) and [MoO(bdt)(bdtCl2)](2-) (11), respectively. New
      sulfido/oxo molybdenum complexes were characterized by (1)H NMR, IR, ESI-MS,
      Raman, and UV-vis spectroscopies; cyclic voltammetry; and elemental analysis, and
      crystal structures of 2, 3, 5, 7, and 8 were determined by X-ray analysis.

PMID- 18826212
TI  - Site selectivity in the protonation of a phosphinito bridged Pt(I)-Pt(I) complex:
      a combined NMR and density-functional theory mechanistic study.
AB  - The protonation of the dinuclear phosphinito bridged complex [(PHCy2)Pt(mu
      PCy2){kappa(2)P,O-mu-P(O)Cy2}Pt(PHCy2)] (Pt-Pt) (1) by Bronsted acids affords
      hydrido bridged Pt-Pt species the structure of which depends on the nature and on
      the amount of the acid used. The addition of 1 equiv of HX (X = Cl, Br, I) gives
      products of formal protonation of the Pt-Pt bond of formula syn-[(PHCy2)(X)Pt(mu
      PCy2)(mu-H)Pt(PHCy2){kappaP-P(O)Cy2}] (Pt-Pt) (5, X = Cl; 6, X = Br; 8, X = I),
      containing a Pt-X bond and a dangling kappa P-P(O)Cy2 ligand. Uptake of a second
      equivalent of HX results in the protonation of the P(O)Cy2 ligand with formation
      of the complexes [(PHCy2)(X)Pt(mu-PCy2)(mu-H)Pt(PHCy2){kappaP-P(OH)Cy2}]X (Pt-Pt)
      (3, X = Cl; 4, X = Br; 9, X = I). Each step of protonation is reversible, thus
      reactions of 3, 4, with NaOH give, first, the corresponding neutral complexes 5,
      6, and then the parent compound 1. While the complexes 3 and 4 are indefinitely
      stable, the iodine analogue 9 transforms into anti-[(PHCy2)(I)Pt(mu-PCy2)(mu
      H)Pt(PHCy2)(I)] (Pt-Pt) (7) deriving from substitution of an iodo group for the
      P(OH)Cy2 ligand. Complexes 3 and 4 are isomorphous crystallizing in the triclinic
      space group P1 and show an intramolecular hydrogen bond and an interaction
      between the halide counteranion and the POH hydrogen. The occurrence of such an
      interaction also in solution was ascertained for 3 by (35)Cl NMR. Multinuclear
      NMR spectroscopy (including (31)P-(1)H HOESY) and density-functional theory
      calculations indicate that the mechanism of the reaction starts with a prior
      protonation of the oxygen with formation of an intermediate (12) endowed with a
      six membered Pt(1)-X...H-O-P-Pt(2) ring that evolves into thermodynamically
      stable products featuring the hydride ligand bridging the Pt atoms. Energy
      profiles calculated for the various steps of the reaction between 1 and HCl
      showed very low barriers for the proton transfer and the subsequent rearrangement
      to 12, while a barrier of 29 kcal mol(-1) was found for the transformation of 12
      into 5.

PMID- 18826213
TI  - Hydrothermal synthesis, crystal structure, and magnetic properties of a new
      inorganic vanadium(III) phosphate with a chain structure.
AB  - A new vanadium(III) phosphate, Na3V(OH)(HPO4)(PO4), has been synthesized by using
      mild hydrothermal conditions under autogeneous pressure. This material represents
      a very rare example of sodium vanadium(III) phosphate with a chain structure. The
      crystal structure has been determined by refinement of powder X-ray diffraction
      data, starting from the atomic coordinates of an isotypic compound,
      Na3Al(OH)(HPO4)(PO4), which was obtained under high temperature and high
      pressure. The phase crystallizes in monoclinic space group C2/m (No. 12) with
      lattice parameters a = 15.423(9) A, b = 7.280(0) A, c = 7.070(9) A, beta =
      96.79(7) degrees, V = 788.3(9) A(3), and Z = 4. The structure consists of one
      dimensional chains composed of corner-sharing VO5(OH) octahedra running along the
      b direction. They are decorated by isolated PO4 and HPO4 tetrahedra sharing two
      of their corners with the ones of the vanadium octahedra. The interconnection
      between the chains is assured by three crystallographically distinct Na(+)
      cations. Magnetic investigation confirms the 3+ oxidation state of the vanadium
      ions and reveals an antiferromagnetic arrangement between those ions through the
      chain.

PMID- 18826214
TI  - Tetravalent silicon connectors MenSi(p-C6H4CO2H)(4-n) (n = 0, 1, 2) for the
      construction of metal-organic frameworks.
AB  - A series of silicon-centered connecting units, Me(n)Si(p-C6H4CO2H)(4-n) (n = 0,
      1, 2), have been prepared and their coordination polymers with Zn(II) metal atoms
      studied. The tetra-acid L1 (n = 0) acts as a tetrahedral node and reacts with
      Zn(II) centers to give 1, a novel interpenetrating 3D network containing
      distorted tetrahedral bimetallic secondary building units (SBUs). The triacid L2
      (n = 1) acts as a trigonal pyramidal node and forms an intercalated 2D layered
      network, 2, with Zn(II) ions, containing distorted octahedral tetranuclear SBUs.
      Last, the bent diacid L3 (n = 2) reacts with Zn(II) centers to give 3, a
      corrugated 2D layered structure containing 1D zinc hydroxo chains. Together these
      three new coordination polymers demonstrate the potential versatility of
      tetravalent silicon containing connecting ligands for metal-organic framework
      construction.

PMID- 18826215
TI  - Magnetic spongelike behavior of 3D ferrimagnetic {[Mn(II)(imH)]2[Nb(IV)(CN)8]}n
      with Tc = 62 K.
AB  - Fully reversible room temperature dehydration of 3D
      {Mn(II)2(imH)2(H2O)4[Nb(IV)(CN)8] x 4 H2O}n (1; imH = imidazole) of Tc = 25 K
      results in the formation of 3D ferrimagnet {[Mn(II)(imH)]2[Nb(IV)(CN)8]}n (2),
      with Tc = 62 K, the highest ever known for octacyanometalate-based compounds. The
      dramatic magnetostructural modifications in 2 provide the first example of
      magnetic spongelike behavior in an octacyanometallate-based assembly.

PMID- 18826216
TI  - Cubic nonlinear optical properties of platinum-terminated polyynediyl chains.
AB  - The wavelength dependence of the cubic nonlinearity of ligated platinum
      terminated polyynes trans, trans-{(p-MeC6H4)3P}2(p-MeC6H4)Pt(C[triple bond]C)n
      Pt(p-C6H4Me){P(p-C6H4Me)3}2 (n = 3-6, 8, 10, 12) has been examined by femtosecond
      Z-scan studies in the wavelength range 520-1500 nm and the results rationalized
      by density functional theory calculations on the model complexes trans, trans
      (H3P)2(C6H5)Pt(C[triple bond]C)n Pt(C6H5)(PH3)2 (n = 2-8, 10, 12). Although the
      final states for one- and two-photon transitions are not the same in these
      centrosymmetric molecules, the Z-scan studies reveal coincidences in one-photon
      absorption with features in the frequency dependencies of both real and imaginary
      parts of the cubic hyperpolarizability, as well as inflections in the frequency
      dependencies of the real part of gamma that correspond to resonances in the
      imaginary part of gamma. The theoretical studies suggest that the linear
      absorption spectra are dominated by X(1)A g --> n(1)B(3u) transitions, with the
      first state of B(3u) symmetry playing a steadily diminishing role upon oligoyne
      chain lengthening. The theoretical studies also predict a red-shift of two-photon
      absorption (TPA) profile with increasing conjugation length, and a significant
      enhancement on proceeding from the shortest to the longest chromophore, trends
      that are observed experimentally. The experimental low-energy TPA maxima for
      these complexes can be approximated by a simple Gaussian profile. The sp-carbon
      chain-length dependence of linear and nonlinear absorption maxima enable an
      estimate (neglecting saturation) of 660 and 1000 nm for the infinite carbon
      chain, carbyne.

PMID- 18826217
TI  - 24- and 26-membered macrocyclic diorganotin(IV) bis-dithiocarbamate complexes
      with N,N'-disubstituted 1,3- and 1,4-bis(aminomethyl)benzene and 1,1'
      bis(aminomethyl)ferrocene as spacer groups.
AB  - The potassium bis-dithiocarbamate (bis-dtc) salts of 1,3
      bis(benzylaminomethyl)benzene (1,3-Bn-ambdtc), 1,3-bis(iso
      butylaminomethyl)benzene (1,3-(i)Bu-ambdtc), 1,4-bis(benzylaminomethyl)benzene
      (1,4-Bn-ambdtc), and 1,4-bis(iso-butylaminomethyl)benzene (1,4-(i)Bu-ambdtc) were
      reacted with three different diorganotin dichlorides (R2SnCl2 with R = Me, (n)Bu,
      and Ph) in 1:1 stoichiometric ratios to give the corresponding diorganotin bis
      dithiocarbamates. Additionally, the dimethyltin bis-dithiocarbamate of 1,1'
      bis(benzylaminomethyl)ferrocene (1,1'-Bn-amfdtc) was prepared. The resulting
      complexes have been characterized as far as possible by elemental analysis,
      FAB(+) mass spectrometry, IR and NMR ((1)H, (13)C, and (119)Sn) spectroscopy, and
      single-crystal X-ray diffraction, showing that the tin complexes are dinuclear 24
      and 26-membered macrocyclic species of composition [{R2Sn(bis-dtc)}2]. As shown
      by (119)Sn NMR spectroscopy, the tin centers are hexa-coordinated in all cases;
      however, two different coordination environments are possible, as detected by
      single-crystal X-ray diffraction. In the dimethyltin derivatives of 1,3-Bn
      ambdtc, 1,3-(i)Bu-ambdtc, 1,4-Bn-ambdtc, and 1,1'-Bn-amfdtc and the di-n-butyltin
      derivative of 1,3-(i)Bu-ambdtc, the metal atoms are embedded in skewed
      trapezoidal-bipyramidal coordination polyhedra with asymmetrically coordinating
      trans-oriented dtc groups. In contrast, in the diphenyltin derivative 1,3-(i)Bu
      ambdtc, the metal centers have distorted octahedral coordination with
      symmetrically coordinating cis-oriented dtc functions. Thus, for the complexes
      derived from 1,3-Bn/(i)Bu-ambdtc, two different macrocyclic structures were
      observed. In the dimethyl- and di-n-butyltin derivatives, the bridging bis-dtc
      ligands adopt U-shaped conformations, while in the case of the diphenyltin
      derivative, the conformation is L-shaped. Furthermore, two different macrocyclic
      ring conformations can occur, which differ in the spatial orientation of the
      substituents attached to the nitrogen atoms (Bn or (i)Bu). The dimethyltin
      derivatives of 1,4-Bn-ambdtc and 1,1'-Bn-amfdtc have cavities, in which aromatic
      rings are accommodated in the solid state.

PMID- 18826218
TI  - Synthesis of Cp-Re complexes via olefinic C-H activation and successive formation
      of cyclopentadienes.
AB  - Treatment of an alpha,beta-unsaturated ketimine with an alpha,beta-unsaturated
      carbonyl compound in the presence of a rhenium complex, Re2(CO)10, gave a
      cyclopentadienyl-rhenium complex. This reaction proceeds via rhenium-catalyzed C
      H bond activation of an olefinic C-H bond, insertion of an alpha,beta-unsaturated
      carbonyl compound into a Re-C bond of the alkenylrhenium intermediate,
      intramolecular nucleophilic cyclization, reductive elimination, elimination of
      aniline to give a cyclopentadiene derivative, followed by the formation of a
      cyclopentadienyl-rhenium complex from the cyclopentadiene derivative and the
      rhenium complex.

PMID- 18826219
TI  - Reactions of strained hydrocarbons with alkene and alkyne metathesis catalysts.
AB  - Here we describe the metathesis reactions of a strained eight-membered ring that
      contains both alkene and alkyne functionality. We find that the alkyne metathesis
      catalyst produces polymer through a ring-opening alkyne metathesis reaction that
      is driven by the strain release from the monomer. The strained monomer provides
      unusual reactivity with ruthenium-based alkene metathesis catalysts. We isolate a
      discrete trimeric species a Dewar benzene derivative that is locked in this form
      through an unsaturated cyclophane strap.

PMID- 18826220
TI  - Imaging induction of cytoprotective enzymes in intact human cells: coumberone, a
      metabolic reporter for human AKR1C enzymes reveals activation by panaxytriol, an
      active component of red ginseng.
AB  - We here present an optical method for monitoring the activity of the inducible
      aldo-keto reductases AKR1C2 and AKR1C3 in living human cells. The induction of
      these enzymes is regulated by the antioxidant response element (ARE), as
      demonstrated in recent literature, which in turn is dependent on the
      transcription factor Nrf2. The activation of ARE leads to the transcription of a
      coalition of cytoprotective enzymes and thus represents an important target for
      the development of new therapies in the area of neurodegenerative diseases and
      cancer. Through the use of Coumberone, a metabolic fluorogenic probe, and isoform
      selective inhibitors, the upregulation of cellular stress markers AKR1C2 and
      AKR1C3 can be quantitatively measured in the presence of ARE activator compounds,
      via either a fluorimetric assay or fluorescence microscopy imaging of intact
      cells. The method has both high sensitivity and broad dynamic range, as
      demonstrated by induction studies in three cell lines with dramatically different
      metabolic capabilities (transfected monkey kidney COS-1 cells, human
      neuroblastoma IMR-32 cells, and human liver HepG2 cells). We applied the new
      method to examine a number of neurotrophic natural products (spirotenuipesine A,
      spirotenuipesine B, scabronine G-methylester, and panaxytriol), and discovered
      that panaxytriol, an active component of red ginseng extracts, is a potent ARE
      inducer. The upregulation of AKR1C enzymes, induced by chemically homogeneous
      panaxytriol, was partially dependent on PKC and PI3K kinases as demonstrated by
      the application of selective inhibitors. This cellular mechanism may account for
      panaxytriol's neurotrophic, neuroprotective, and anticancer properties. The
      protective effects of ARE inducers against tumorgenesis and neurodegeneration
      fuel the growing interest in this area of research and the method described here
      will greatly enable these endeavors.

PMID- 18826221
TI  - Bacterial membranes as predictors of antimicrobial potency.
AB  - A wide range of chemical structures having antimicrobial activity have been
      studied in an effort to treat the increasing emergence of bacteria that are
      resistant to traditional antibiotics. These agents have varying degrees of
      toxicity against different bacterial species. We demonstrate, using members of a
      novel class of antimicrobial agents, the oligomers of acyllysine, that one cause
      for the difference in species selectivity is the ability to induce the clustering
      of anionic lipids, resulting in their segregation into domains. This phenomenon
      occurs only in bacterial membranes composed of both anionic and zwitterionic
      lipids and not with bacteria whose membrane lipids are largely anionic. As a
      consequence it can be predicted which bacterial species will be most affected by
      antimicrobial agents that function principally by this mechanism. This finding
      allows for the design of new antibiotics with selective toxicity against
      different groups of bacteria.

PMID- 18826222
TI  - Multiplexed screening of cellular uptake of gold nanoparticles using laser
      desorption/ionization mass spectrometry.
AB  - Gold nanoparticles (AuNPs) are highly promising candidates as drug delivery
      agents into cells of interest. We describe for the first time the multiplexed
      analysis of nanoparticle uptake by cells using mass spectrometry. We demonstrate
      that the cellular uptake of functionalized gold nanoparticles with cationic or
      neutral surface ligands can be readily determined using laser
      desorption/ionization mass spectrometry of cell lysates. The surface ligands have
      "mass barcodes" that allow different nanoparticles to be simultaneously
      identified and quantified at levels as low as 30 pmol. Using this method, we find
      that subtle changes to AuNP surface functionalities can lead to measurable
      changes in cellular uptake propensities.

PMID- 18826223
TI  - Diverse polymorphism of G-quadruplexes as a kinetic phenomenon.
AB  - Knowledge of forces that drive conformational transitions of G-quadruplexes is
      crucial for understanding the molecular basis of several key cellular processes.
      It can only be acquired by combining structural, thermodynamic and kinetic
      information. Existing biophysical and structural evidences on polymorphism of
      intermolecular G-quadruplexes have shown that the formation of a number of these
      structures is a kinetically controlled process. Reported kinetic models that have
      been used to describe the association of single strands into quadruplex
      structures seem to be inappropriate since the corresponding model-predicted
      activation energies turn out to be negative. By contrast, we propose here a novel
      kinetic model that successfully describes experimentally monitored
      folding/unfolding transitions of G-quadruplexes and gives positive activation
      energies for all elementary steps, including those describing association of two
      single strands into bimolecular quadruplex structures. It is based on a combined
      thermodynamic and kinetic investigation of polymorphic behavior of bimolecular G
      quadruplexes formed from d(G4T4G4) and d(G4T4G3) strands in the presence of Na(+)
      ions, monitored by spectroscopic (UV, CD) and calorimetric (DSC) techniques.
      According to our experiment and model analysis the topology of the measured G
      quadruplexes is clearly flexible with the conformational forms that respond to
      the rate of temperature change at which global unfolding/folding transitions
      occur.

PMID- 18826224
TI  - Importance of the number of acid molecules and the strength of the base for
      double-ion formation in (H2SO4)m x base x (H2O)6 clusters.
AB  - Sulfuric acid and water clusters are important for new particle formation in the
      atmosphere. Recent experimental studies demonstrate that critical clusters in
      diverse atmospheric environments contain two acid molecules and may also include
      additional N-containing molecules (i.e., a base). We use first-principles
      molecular dynamics simulations to show that the presence of two sulfuric acid
      molecules in (H2SO4)m x base x (H2O)6 clusters is always sufficient to form a
      double ion, whereas a single acid molecule, even in the presence of a base, is
      not.

PMID- 18826225
TI  - Selective photochemical functionalization of surfactant-dispersed single wall
      carbon nanotubes in water.
AB  - Ultraviolet (UV) irradiation of single wall carbon nanotubes (SWCNTs)
      individually dispersed in surfactants leads to diameter and type-selective
      photohydroxylation of the nanotubes. Photohydroxylation of first semiconductor
      and then small diameter metallic SWCNTs was confirmed after 254 nm UV irradiation
      in acidic, neutral, and basic aqueous solutions at ambient and elevated
      temperatures. The increased oxygen content of the SWCNTs after UV irradiation, as
      detected by X-ray photoelectron spectroscopy, suggests that SWCNTs were
      hydroxylated by reaction with water. Attenuated total reflectance Fourier
      transform infrared analysis provides evidence of hydroxyl functional groups on
      their surface. This photochemical reaction is impeded by molecular oxygen and
      appears to involve a reactive intermediate generated in the vicinity of
      semiconducting SWCNTs. This represents a noncontaminating selective reaction in
      the liquid phase that uses an intrinsic property of the tubes.

PMID- 18826226
TI  - Selective adsorption and separation of ortho-substituted alkylaromatics with the
      microporous aluminum terephthalate MIL-53.
AB  - The metal-organic framework MIL-53(Al) was tested for selective adsorption and
      separation of xylenes and ethylbenzene, ethyltoluenes, and cymenes using batch,
      pulse chromatographic, and breakthrough experiments. In all conditions tested,
      MIL-53 has the largest affinity for the ortho-isomer among each group of
      alkylaromatic compounds. Separations of the ortho-compounds from the other
      isomers can be realized using a column packed with MIL-53 crystallites. As
      evidenced by Rietveld refinements, specific interactions of the xylenes with the
      pore walls of MIL-53 determine selectivity. In comparison with the structurally
      similar metal-organic framework MIL-47, the selectivities among alkylaromatics
      found for MIL-53 are different. Separation of ethyltoluene and cymene isomers is
      more effective on MIL-53 than on MIL-47; the pores of MIL-53 seem to be a more
      suitable environment for hosting the larger ethyltoluene and cymene isomers than
      those of MIL-47.

PMID- 18826227
TI  - Akt/FOXO3a/SIRT1-mediated cardioprotection by n-tyrosol against ischemic stress
      in rat in vivo model of myocardial infarction: switching gears toward survival
      and longevity.
AB  - Moderate consumption of wine has been associated with decreased risk of
      cardiovascular events. Recently we have shown that white wine is equally as
      cardioprotective as red wine. However, unlike resveratrol (polyphenol in red
      wine), the white wine component, n-tyrosol [2-(4-hydroxyphenyl)ethanol] has not
      been explored for its cardioprotective effect and mechanism of action. Therefore,
      the present study was designed to evaluate the effect of tyrosol treatment (5
      mg/kg/day for 30 days) on myocardial ischemic stress in a rat in vivo model of
      Myocardial Infarction (MI) and to identify key molecular targets involved in this
      mechanism. MI was induced by Left Anterior Descending (LAD) coronary artery
      ligation. Reduced infarct size (32.42 vs 48.03%) and cardiomyocyte apoptosis (171
      vs 256 counts/100 HPF) were observed along with improvement in the myocardial
      functional parameters such as LVIDs (5.89 vs 6.58 mm), ejection fraction (51.91
      vs 45.09%), and fractional shortening (28.46 vs 23.52%) as assessed by
      echocardiography in the tyrosol-treated animals when compared to the nontreated
      controls. We have also observed significant increase in the phosphorylation of
      Akt (1.4-fold), eNOS (3-fold) and FOXO3a (2.6-fold). In addition, tyrosol induced
      the expression of longevity protein SIRT1 (3.2-fold) in the MI group as compared
      to the non-treated MI control. Therefore tyrosol's SIRT1, Akt and eNOS activating
      power adds another dimension to the white wine research, because it adds a great
      link to the French paradox. In conclusion these findings suggest that tyrosol
      induces myocardial protection against ischemia related stress by inducing
      survival and longevity proteins that may be considered as anti-aging therapy for
      the heart. However, human intervention studies would be necessary before
      establishing any recommendations about dietary habits for tyrosol intake or
      administration of dietary supplements containing tyrosol.

PMID- 18826228
TI  - Purification of curcumin, demethoxycurcumin, and bisdemethoxycurcumin by high
      speed countercurrent chromatography.
AB  - Curcuminoids are substances of great interest because of their important
      pharmacological activities, particularly anti-inflammatory, anticarcinogenic, and
      anti-Alzheimer's activities. In this study, we report the first procedure and
      effect of processing for the high, efficient, and useful purification of
      curcumin, demethoxycurcumin, and bisdemethoxycurcumin from turmeric powder.
      Purification involves high-speed countercurrent chromatographic (HSCCC)
      separation of these curcuminoids using a simple two-phase solvent system composed
      of n-hexane/chloroform/methanol/water (5/10/7.5/2.5, v/v). The HSCCC-fractionated
      effluent peaks indicated that the peak resolutions were 1.7 between curcumin and
      demethoxycurcumin and 2.1 between demethoxycurcumin and bisdemethoxycurcumin for
      25 mg of loaded turmeric powder. These purified substances were analyzed by
      liquid chromatography-tandem mass spectrometry with scan and daughter scan
      negative modes, and the wide absorbance from 200 to 500 nm was monitored by
      photodiode array detection. The separation yielded 1.1 mg of curcumin, 0.6 mg of
      demethoxycurcumin, and 0.9 mg of bisdemethoxycurcumin (>98% purity). Moreover,
      the antioxidant effect of curcuminoids was measured by a 1,1-diphenyl-2
      picrylhydrazil assay. The order of antioxidant activity was purified curcumin >
      purified demethoxycurcumin > purified bisdemethoxycurcumin > turmeric powder.
      Curcumin, demethoxycurcumin, and bisdemethoxycurcumin can be used for various
      evaluations of their pharmacological activities.

PMID- 18826229
TI  - Metabolic transformation of sesamol and ex vivo effect on 2,2'-azo-bis(2
      amidinopropane)dihydrochloride-induced hemolysis.
AB  - Sesamol (3,4-methylenedioxyphenol), a phenolic constituent in roasted sesame, was
      reported to exhibit various beneficial activities. To understand the metabolic
      transformation of sesamol in vivo, rats were given sesamol intravenously and
      orally. The blood samples were withdrawn via cardiopuncture at specific time
      points. The serum samples were assayed by high-performance liquid chromatography
      method before and after hydrolysis with sulfatase and beta-glucuronidase. Our
      results indicated that following either intravenous or oral administration,
      sesamol declined rapidly and the sulfate/glucuronide of sesamol emerged
      instantaneously. The peak serum concentration and systemic exposure of sesamol
      were markedly lower than sesamol sulfate/glucuronide. Ex vivo evaluation revealed
      that sesamol exerted profoundly higher capability against 2,2'-azo-bis(2
      amidinopropane)dihydrochloride-induced hemolysis than the serum metabolites. In
      conclusion, sulfate and glucuronide of sesamol were the principle metabolites of
      sesamol in the bloodstream of rats. The conjugated metabolites of sesamol warrant
      more bioactivity investigations to understand the in vivo effect of sesamol.

PMID- 18826230
TI  - Simultaneous determination of saccharin and aspartame in commercial noncaloric
      sweeteners using the PLS-2 multivariate calibration method and validation by
      capillary electrophoresis.
AB  - A new method to determine a mixture for sweetener sodium saccharin and aspartame
      in commercial noncaloric sweeteners is proposed. A classical full factorial
      design for standards was used in the calibration step to build the partial least
      squares (PLS-2) model. Instrumental data were obtained by means of UV-visible
      spectrophotometry. Salicylic acid was used as an internal standard to evaluate
      the adjustment of the real samples to the PLS model. The concentration of
      analytes in the commercial samples was evaluated using the obtained model by UV
      spectral data. The PLS-2 method was validated by capillary zone electrophoresis
      (CZE), finding in all cases a relative error of less than 11% between the PLS-2
      and the CZE methods. The proposed procedure was applied successfully to the
      determination of saccharin and aspartame in noncaloric commercial sweeteners.

PMID- 18826231
TI  - One-pot reaction as an efficient method for rigid molecular tweezers.
AB  - Rigid molecular tweezers are compounds of increasing scientific interest. As the
      structural requirements for such compounds are highly specific, few types of
      these tweezers are thus far known. The preparation of examples of rigid large
      pincered molecular tweezers based on bis Troger's bases derived from 1,4
      benzenediamine is described. In addition, evidence is presented of the different
      binding abilities of the diastereoisomers of such compounds.

PMID- 18826232
TI  - Synthesis and characterization of coumarin-based spiropyran photochromic
      colorants.
AB  - Two coumarin-based spiropyran derivatives were synthesized and characterized in
      two steps to explore their photochromic properties. Both prepared compounds are
      sensitive to UV light and change colors upon irradiation. The resulting
      photogenerated zwitterions revert to the original compounds while being heated. A
      new family of organic photochromic colorants is introduced.

PMID- 18826233
TI  - Is donor-acceptor hydrogen bonding necessary for 4,6-O-benzylidene-directed beta
      mannopyranosylation? Stereoselective synthesis of beta-C-mannopyranosides and
      alpha-C-glucopyranosides.
AB  - 2,3-Di-O-benzyl-4,6-O-benzylidene-thiohexopyranosides, on activation with 1
      benzenesulfinyl piperidine and triflic anhydride, react with allyl silanes and
      stannanes, and with silyl enolethers to give C-glycosides. In the mannose series
      the beta-isomers are formed selectively whereas the glucose series provides the
      alpha-anomers. This selectivity pattern parallels that of O-glycoside formation
      and eliminates the need to consider donor-acceptor hydrogen bonding in the
      formation of the O-glycosides.

PMID- 18826234
TI  - Studies on the stereoselective synthesis of C-allyl glycosides.
AB  - An investigation was carried out to explore the use of sulfoxide donors as common
      precursors to stereoisomeric C-glycoconjugates of glycoprotein and glycolipid
      tumor antigens. A study focusing on the effects of reaction conditions and
      substrate structure on the stereoselectivity of allylation was carried out.
      Although conditions were realized to selectively afford alpha-allylation products
      in good to excellent yields, the search for conditions favoring beta-selectivity
      proved less successful.

PMID- 18826235
TI  - Copper iodide-catalyzed cyclization of (Z)-chalcogenoenynes.
AB  - We present here our results of the efficient copper-catalyzed cyclizations of
      chalcogenoenynes and establish a route to obtain 3-substituted chalcogenophenes
      in good to excellent yields. In addition, the obtained chalcogenophenes were
      readily transformed to more complex products using the palladium-catalyzed cross
      coupling reactions with boronic acids to give Suzuki-type products in good
      yields.

PMID- 18826236
TI  - Highly regioselective intermolecular arylation of 1,2,3,4-tetrahydropyridines.
AB  - Using a catalytic amount of PdCl2(dppf) x CH2Cl2 in combination with Ag3PO4 and
      NaOAc, a range of arylated 1,2,3,4-tetrahydropyridines are synthesized in good
      yields and with complete selectivity at the beta-position. The reaction is
      compatible with a variety of electron-donating and electron-withdrawing aryl
      iodides as well as with heteroaryl iodides. The application of these
      tetrahydropyridines toward the synthesis of polysubstituted piperidines is also
      demonstrated.

PMID- 18826238
TI  - Liquid chromatography of theta-shaped and three-armed star
      poly(tetrahydrofuran)s: theory and experimental evidence of topological
      separation.
AB  - A theoretical background is provided for the methods of the analysis and
      topological separation of complex macrocyclic polymers by means of size exclusion
      chromatography (SEC), liquid adsorption chromatography, and liquid chromatography
      at the critical condition. We focus on a particular problem of the separation of
      theta-shaped polymers from its three-armed star analogues. Based on the theory,
      we simulate chromatograms for model mixtures of polydisperse theta- and star
      polymers and analyze conditions for good separation of these polymers by
      topology. A theory is compared with the behavior of star- and theta-shaped
      poly(THF)s in size exclusion and interactive chromatography, and a good
      qualitative agreement between theory and experiment is observed. In particular,
      it is shown that in both SEC and interactive chromatography theta-polymers elute
      after the corresponding stars of the same molar mass. According to theory and
      experiment, chromatography under the critical and near-critical interaction
      conditions is especially promising for the separation of polydisperse macrocyclic
      polymers from their linear or branched analogues.

PMID- 18826239
TI  - Giant magnetoresistance sensors. 1. Internally calibrated readout of scanned
      magnetic arrays.
AB  - This paper describes efforts aimed at setting the stage for the application of
      giant magnetoresistance sensor (GMRs) networks as readers for quantification of
      biolytes selectively captured and then labeled with superparamagnetic particles
      on a scanned chip-scale array. The novelty and long-range goal of this research
      draws from the potential development of a card-swipe instrument through which an
      array of micrometer-sized, magnetically tagged addresses (i.e., a sample stick)
      can be interrogated in a manner analogous to a credit card reader. This work
      describes the construction and testing of a first-generation instrument that uses
      a GMR sensor network to read the response of a "simulated" sample stick. The
      glass sample stick is composed of 20-nm-thick films of permalloy that have square
      or rectangular lateral footprints of up to a few hundred micrometers. Experiments
      were carried out to gain a fundamental understanding of the dependence of the GMR
      response on the separation between, and planarity of, the scanned sample stick
      and sensor. Results showed that the complex interplay between these
      experimentally controllable variables strongly affect the shape and magnitude of
      the observed signal and, ultimately, the limit of detection. This study also
      assessed the merits of using on-sample standards as internal references as a
      facile means to account for small variations in the gap between the sample stick
      and sensor. These findings were then analyzed to determine various analytical
      figures of merit (e.g., limit of detection in terms of the amount of magnetizable
      material on each address) for this readout strategy. An in-depth description of
      the first-generation test equipment is presented, along with a brief discussion
      of the potential widespread applicability of the concept.

PMID- 18826240
TI  - Metalation states versus enzyme activities of Cu, Zn-superoxide dismutase probed
      by electrospray ionization mass spectrometry.
AB  - Cu, Zn-superoxide dismutase (SOD-1), an enzyme that catalyzes the
      disproportionation reaction of superoxide to produce oxygen and hydrogen
      peroxide, thereby protecting cells from oxidative stress, is a homodimer that
      coordinates one copper and one zinc ion per monomer. Cu (2+) and Zn (2+) ions
      play important roles in enzyme activity and structural stability, respectively.
      In addition, dimer formation is also essential for fulfilling the function of SOD
      1. We here report on the reconstitution and enzyme activities of several
      metalation states of SOD-1 (Cu 4-, Cu 3Zn-, and Cu 2Zn 2-homodimers). Each
      metalation state of the reconstituted SOD-1 could be unambiguously differentiated
      by electrospray ionization mass spectrometry, the metal ions of which had been
      completely replaced by 99 atom % (63)Cu and (68)Zn stable isotopes. It was found
      that (1) the Cu 4-dimer possessed 84% of the activity of the native enzyme, (2)
      the Cu-site resisted being coordinated with Zn (2+) ions while the Zn-site could
      be bound with Cu (2+) ions, and (3) the simultaneous addition of the Cu (2+) and
      Zn (2+) ions to generate a fully metalated form produced the multiply metalated
      SOD-1 (Cu 4-, Cu 3Zn-, and Cu 2Zn 2-dimers), which were clearly distinguishable
      from one another by the use of the stable isotopes, while the sequential addition
      of Zn (2+) followed by the Cu (2+) ion predominantly produced a Cu 2Zn 2-dimer
      comparable to the native enzyme.

PMID- 18826241
TI  - Giant magenetoresistive sensors. 2. Detection of biorecognition events at self
      referencing and magnetically tagged arrays.
AB  - Microfabricated devices formed from alternating layers of magnetic and
      nonmagnetic materials at combined thicknesses of a few hundred nanometers exhibit
      a phenomenon known as the giant magnetoresistance effect. Devices based on this
      effect are known as giant magnetoresistive (GMR) sensors. The resistance of a GMR
      is dependent on the strength of an external magnetic field, which has resulted in
      the widespread usage of such platforms in high-speed, high-data density storage
      drives. The same attributes (i.e., sensitivity, small size, and speed) are also
      important embodiments of many types of bioanalytical sensors, pointing to an
      intriguing opportunity via an integration of GMR technology, magnetic labeling
      strategies, and biorecognition elements (e.g., antibodies). This paper describes
      the utilization of GMRs for the detection of streptavidin-coated magnetic
      particles that are selectively captured by biotinylated gold addresses on a 2 x
      0.3 cm sample stick. A GMR sensor network reads the addresses on a sample stick
      in a manner that begins to emulate that of a "card-swipe" system. This study also
      takes advantage of on-sample magnetic addresses that function as references for
      internal calibration of the GMR response and as a facile means to account for
      small variations in the gap between the sample stick and sensor. The magnetic
      particle surface coverage at the limit of detection was determined to be
      approximately 2%, which corresponds to approximately 800 binding events over the
      200 x 200 microm capture address. These findings, along with the potential use of
      streptavidin-coated magnetic particles as a universal label for antigen detection
      in, for example, heterogeneous assays, are discussed.

PMID- 18826242
TI  - Time-dependent profiling of metabolites from Snf1 mutant and wild type yeast
      cells.
AB  - The effect of sampling time in the context of growth conditions on a dynamic
      metabolic system was investigated in order to assess to what extent a single
      sampling time may be sufficient for general application, as well as to determine
      if useful kinetic information could be obtained. A wild type yeast strain (W) was
      compared to a snf1Delta mutant yeast strain (S) grown in high-glucose medium (R)
      and in low-glucose medium containing ethanol (DR). Under these growth conditions,
      different metabolic pathways for utilizing the different carbon sources are
      expected to be active. Thus, changes in metabolite levels relating to the carbon
      source in the growth medium were anticipated. Furthermore, the Snf1 protein
      kinase complex is required to adapt cellular metabolism from fermentative R
      conditions to oxidative DR conditions. So, differences in intracellular
      metabolite levels between the W and S yeast strains were also anticipated. Cell
      extracts were collected at four time points (0.5, 2, 4, 6 h) after shifting half
      of the cells from R to DR conditions, resulting in 16 sample classes (WR, WDR,
      SR, SDR) x (0.5, 2, 4, 6 h). The experimental design provided time course data,
      so temporal dependencies could be monitored in addition to carbon source and
      strain dependencies. Comprehensive two-dimensional (2D) gas chromatography
      coupled to time-of-flight mass spectrometry (GC x GC-TOFMS) was used with
      discovery-based data mining algorithms ( Anal. Chem. 2006, 78, 5068-5075 (ref 1);
      J. Chromatogr., A 2008, 1186, 401-411 (ref 2)) to locate regions within the 2D
      chromatograms (i.e., metabolites) that provided chemical selectivity between the
      16 sample classes. These regions were mathematically resolved using parallel
      factor analysis to positively identify the metabolites and to acquire
      quantitative results. With these tools, 51 unique metabolites were identified and
      quantified. Various time course patterns emerged from these data, and principal
      component analysis (PCA) was utilized as a comparison tool to determine the
      sources of variance between these 51 metabolites. The effect of sampling time was
      investigated with separate PCA analyses using various subsets of the data. PCA
      utilizing all of the time course data, averaged time course data, and each
      individual time point data set independently were performed to discern the
      differences. For the yeast strains examined in the current study, data collection
      at either 4 or 6 h provided information comparable to averaged time course data,
      albeit with a few metabolites missing using a single sampling time point.

PMID- 18826243
TI  - Theoretical analysis of microscopic ohmic drop effects on steady-state and
      transient voltammetry at the disk microelectrode: a quasi-conformal mapping
      modeling and simulation.
AB  - The effect of uncompensated solution resistance on steady-state and transient
      voltammograms at the disk microelectrode was for the first time treated
      theoretically and numerically at the microscopic level using specific quasi
      conformal mapping for the case of absence of electric migration. It has been
      shown that microscopic distributions of electric potential and current density at
      a disk microelectrode affect the voltammetric waves at different degrees across
      the electrode surface due to the variation of elementary resistances and
      elementary current fluxes over the electrode surface which leads to nonlinear
      effects that have not been discussed in existing theoretical treatments of ohmic
      drop at microelectrodes. The analysis of steady state voltammetry in strongly
      resistive media under Nernstian conditions has allowed justification by
      appropriate analytical derivations of the widely used potential-shift correction
      of steady state voltammograms by plotting i vs ( E - iR e).

PMID- 18826244
TI  - Chemometrics-assisted excitation-emission fluorescence spectroscopy on nylon
      membranes. Simultaneous determination of benzo[a]pyrene and dibenz[a,h]anthracene
      at parts-per-trillion levels in the presence of the remaining EPA PAH priority
      pollutants as interferences.
AB  - This work presents a novel approach for the simultaneous ultratrace determination
      of benzo[ a]pyrene and dibenzo[ a,h]anthracene, the two most carcinogenic
      polycyclic aromatic hydrocarbons (PAHs), in a very interfering environment,
      combining the recently discovered ability of the nylon membrane to strongly
      retain and concentrate PAHs on its surface, the sensitivity of molecular
      fluorescence, and the selectivity of second-order chemometric algorithms. The
      fluorescence excitation-emission matrices, directly measured on a nylon-membrane
      surface, are processed by applying parallel factor analysis (PARAFAC) and
      unfolded partial least-squares coupled to residual bilinearization (U-PLS/RBL).
      The superiority of U-PLS/RBL to quantify BaP and DBA at concentrations below 10
      ng L (-1) in the presence of the remaining 14 US EPA (United States Environmental
      Protection Agency) PAHs at total concentrations ranging from 1400 and 14,000 ng L
      (-1) is demonstrated. The present method successfully faces this complex
      challenge without using organic solvents, which are to known produce
      environmental contamination. Finally, the high sensitivity of the present method
      avoids preconcentration and elution steps, considerably decreasing the analysis
      time and the experimental errors. Because the instrumental involved in the
      determination is nonsophisticated, the experiments could be carried out in
      routine laboratories.

PMID- 18826245
TI  - Infrared reflectance-absorbance spectroscopy of thin films formed by forced
      dewetting of solid-fluid interfaces.
AB  - An infrared reflectance-absorbance spectroscopy method for characterizing the
      ultrathin fluid film retained on a surface upon forced dewetting from a fluid has
      been developed for investigation of interfacial molecular structure at reflective
      substrates. This report details the optical considerations and constraints
      necessary to acquire IR spectral data from nanometer-thick films retained upon
      forced dewetting of a solid substrate from a fluid into a vapor-saturated
      environment. The feasibility of this method is demonstrated through successful
      spectral acquisition from Ag surfaces modified with 11-mercaptoundecanol forcibly
      dewet from water. The IR spectral results clearly illustrate that information is
      acquired only from the interfacial region with no contribution from the bulk
      liquid. Residual layer thicknesses calculated from IR absorbance values are
      substantiated by ellipsometry. The spectra make clear that the molecular
      structure of the residual layer is distinctly different from that of the bulk
      liquid, confirming that this method is viable for interfacial structure
      elucidation of thin fluid films at a variety of solid substrates.

PMID- 18826246
TI  - Laser ablation coupled to a flowing atmospheric pressure afterglow for ambient
      mass spectral imaging.
AB  - A plasma-based ambient desorption/ionization mass spectrometry (ADI-MS) source
      was used to perform molecular mass spectral imaging. A small amount of sample
      material was ablated by focusing 266 nm laser light onto a spot. The resulting
      aerosol was transferred by a nitrogen stream to the flowing afterglow of a helium
      atmospheric pressure glow discharge ionization source; the ionized sample
      material was analyzed by a Leco Unique time-of-flight mass spectrometer. Two
      dimensional mass spectral images were generated by scanning the laser beam across
      a sample surface. The total analysis time for a 6 mm (2) surface, which is
      limited by the washout of the ablation chamber, was less than 30 min. With this
      technique, a spatial resolution of approximately 20 microm has been achieved.
      Additionally, the laser ablation configuration was used to obtain depth
      information of over 2 mm with a resolution of approximately 40 microm. The
      combination of laser ablation with the flowing atmospheric pressure afterglow
      source was used to analyze several sample surfaces for a wide variety of analytes
      and with high sensitivity (LOD of 5 fmol for caffeine).

PMID- 18826247
TI  - Solution titration by wall deprotonation during capillary filling of silicon
      oxide nanochannels.
AB  - This paper describes a fundamental challenge when using silicon oxide
      nanochannels for analytical systems, namely the occurrence of a strong proton
      release or proton uptake from the walls in any transient situation such as
      channel filling. Experimentally, when fluorescein solutions were introduced into
      silicon oxide nanochannels through capillary pressure, a distinct bisection of
      the fluorescence was observed, the zone of the fluid near the entrance
      fluoresced, while the zone near the meniscus, was dark. The ratio between the
      zones was found to be constant in time and to depend on ionic strength, pH, and
      the presence of a buffer and its characteristics. Theoretically, using the Gouy
      Chapman-Stern model of the electrochemical double layer, we demonstrate that this
      phenomenon can be effectively modeled as a titration of the solution by protons
      released from silanol groups on the walls, as a function of the pH and ionic
      strength of the introduced solution. The results demonstrate the dominant
      influence of the surface on the fluid composition in nanofluidic experiments, in
      transient situations such as filling, and changes in solvent properties such as
      the pH or ionic strength. The implications of these fundamental properties of
      silicon oxide nanochannels are important for analytical strategies and in
      particular the analysis of complex biological samples.

PMID- 18826248
TI  - Selective electrochemical sensing of glycated hemoglobin (HbA1c) on thiophene-3
      boronic acid self-assembled monolayer covered gold electrodes.
AB  - We report a novel concept of sensing glycated hemoglobin, HbA 1c, which is now
      the most important index for a long-term average blood glucose level, by first
      selectively immobilizing it on the thiophene-3-boronic acid (T3BA) self-assembled
      monolayer (SAM)-covered gold electrode by a selective chemical reaction with
      boronic acid. HbA 1c thus immobilized is then detected by the label-free
      electrochemical impedance spectroscopic (EIS) measurements with a redox probe, an
      equimolar mixture of K 3Fe(CN) 6 and K 4Fe(CN) 6, present. The rate of charge
      transfer between the electrode and the redox probe is shown to be modulated by
      the amount of HbA 1c in the matrix hemoglobin solution due to the blocking effect
      caused by the binding of HbA 1c with boronic acid. Both the formation of a well
      defined T3BA-SAM on the gold surface and the chemical binding of its boronic acid
      with HbA 1c in solution were confirmed by quartz crystal microbalance, atomic
      force microscopy, and EIS experiments.

PMID- 18826249
TI  - Capacitive and solution resistance effects on voltammetric responses of a thin
      redox layer attached to disk microelectrodes.
AB  - A rigorous theoretical analysis of cyclic voltammetry of surface-attached redox
      layers at disk microelectrodes is presented when effects enforced by the solution
      resistance and the electrode capacitance cannot be neglected. This allows a
      precise quantitative evaluation of the influence of each of the current
      components (faradaic, resistive, and capacitive) on the voltammetric shapes
      through numerical simulation. It is shown that the consideration of the solution
      resistance and capacitance effects is crucial for the correct treatment of
      experimental voltammograms at high-voltage scan rates when the resistance is not
      compensated.

PMID- 18826252
TI  - Mitochondrial topoisomerase I sites in the regulatory D-loop region of
      mitochondrial DNA.
AB  - Mitochondrial DNA (mtDNA) is required for mitochondrial activities because it
      encodes key proteins for oxidative phosphorylation and the production of cellular
      ATP. We previously reported the existence of a specific mitochondrial
      topoisomerase gene, Top1mt, in all vertebrates. The corresponding polypeptide
      contains an N-terminal mitochondrial targeting sequence and is otherwise highly
      homologous to the nuclear topoisomerase I (Top1). In this study, we provide
      biochemical evidence of the presence of an endogenous Top1mt polypeptide in human
      mitochondria. Using novel antibodies against Top1mt, we detected the
      corresponding 70 kDa polypeptide in mitochondria but not in nuclear fractions.
      This polypeptide could be trapped to form covalent complexes with mtDNA when
      mitochondria from human cells were treated with camptothecin. Mapping of Top1mt
      sites in the regulatory D-loop region of mtDNA in mitochondria revealed the
      presence of an asymmetric cluster of Top1mt sites confined to a 150 bp segment
      downstream from, and adjacent to, the site at which replication is prematurely
      terminated, generating an approximately 650-base (7S DNA) product that forms the
      mitochondrial D-loop. Moreover, we show that inhibition of Top1mt by camptothecin
      reduces the level of formation of the 7S DNA. These results suggest novel roles
      for Top1mt in regulating mtDNA replication.

PMID- 18826253
TI  - Molecular mechanism of in vitro oligomerization of Dps from Mycobacterium
      smegmatis: mutations of the residues identified by "interface cluster" analysis.
AB  - The irreversible dodecamerization of native Dps trimers from Mycobacterium
      smegmatis, in vitro, is known to be directly associated with the bimodal function
      of this protein. Hence it is important to explore this pathway at the molecular
      level. Two types of trimers, Trimer A (tA) and Trimer B (tB), can be derived from
      the dodecamer due to the inherent 3-fold symmetry of the spherical crystal
      structure. These derived trimers were expressed as protein structure graphs
      (PSGs) using the computed interaction strength among the residues. Interface
      clusters which were identified from PSGs allowed us to convincingly predict E146
      and F47 for further mutation studies. Various single and double mutants were
      constructed and characterized. We were finally able to generate a single mutant
      F47E impaired in dodecamerization and a double mutant E146AF47E as native monomer
      in solution. These two observed results suggest that the two trimers are
      important for dodecamerization and that the residues selected are important for
      the structural stability of the protein in vitro.

PMID- 18826254
TI  - Mechanistic diversity in the RuBisCO superfamily: a novel isomerization reaction
      catalyzed by the RuBisCO-like protein from Rhodospirillum rubrum.
AB  - Some homologues of D-ribulose 1,5-bisphosphate carboxylase/oxygenase (RuBisCO) do
      not catalyze carboxylation and are designated RuBisCO-like proteins (RLPs). The
      RLP from Rhodospirillum rubrum (gi:83593333) catalyzes a novel isomerization
      reaction (overall 1,3-proton transfer reaction; likely, two 1,2-proton transfer
      reactions) that converts 5-methylthio-D-ribulose 1-phosphate to a 3:1 mixture of
      1-methylthioxylulose 5-phosphate and 1-methylthioribulose 5-phosphate. Disruption
      of the gene encoding the RLP abolishes the ability of R. rubrum to utilize 5'
      methylthioadenosine as a sole sulfur source, implicating a new, as-yet
      uncharacterized, pathway for sulfur salvage.

PMID- 18826255
TI  - beta-Hydroxylation of the aspartyl residue in the phytotoxin syringomycin E:
      characterization of two candidate hydroxylases AspH and SyrP in Pseudomonas
      syringae.
AB  - The pseudomonal phytotoxin syringomycin E and related nonribosomal peptides
      contain an L- threo-beta-hydroxyaspartyl residue at the eighth position of the
      lipodepsipeptide backbone as part of a conserved nonproteinogenic tripeptide
      motif. Informatic analysis of the P. syringae genome suggests only one putative
      non-heme iron hydroxylase, AspH. On heterologous expression in Escherichia coli
      AspH shows robust catalytic activity with free L-Asp and L-Asp thioesters to make
      beta-OH-Asp but yields the erythro diastereomer rather than the threo
      configuration that is found in syringomycin. Further analysis of the Syr gene
      cluster indicated that SyrP, previously annotated as the gene regulatory protein
      for the five-gene Syr cluster, is actually homologous to the known non-heme
      mononuclear iron hydroxylase TauD. Indeed, purified SyrP acts on Asp tethered as
      the protein-bound S-pantetheinyl thioester on the eighth module of the SyrE
      megasynthetase. The hydroxylation gives the anticipated L- threo-3-OH-Asp
      diastereomer found in syringomycin. The knockout of syrP abolishes the production
      of the mature syringomycin E, while knockout of aspH has no effect on
      syringomycin production.

PMID- 18826256
TI  - Effect of Hfq on RprA-rpoS mRNA pairing: Hfq-RNA binding and the influence of the
      5' rpoS mRNA leader region.
AB  - The rpoS mRNA encodes a stress response transcription factor in Escherichia coli.
      It is one of a growing number of mRNAs found to be regulated by small RNAs
      (sRNA). Translation initiation of rpoS mRNA is enhanced by two sRNAs, DsrA and
      RprA, that pair to the same site near the rpoS start codon in the presence of the
      Hfq protein. In this work, we examine the interaction of E. coli Hfq with RprA
      and two portions of the rpoS mRNA leader region. One rpoS RNA, rpoS-L, contained
      the entire 565-nucleotide leader region, while the other, rpoS-S, contained the
      199-nucleotide sequence surrounding the start codon. An RNase H assay indicated
      both rpoS RNAs have similar secondary structures in the translation initiation
      region. Hfq formed two complexes with RprA in a gel mobility assay with binding
      parameters similar to values previously determined for DsrA. Unlike DsrA, Hfq
      binding to RprA was inhibited by poly(A) and influenced by Hfq mutations on both
      the distal and proximal surfaces. Hfq increased the level of RprA binding to both
      rpoS RNAs but showed a much larger enhancement when rpoS-L, the entire leader
      region, was examined. The lower affinity of RprA for rpoS-L versus rpoS-S in the
      absence of Hfq suggests that Hfq overcomes an inhibitory structure within rpoS-L
      in stimulating RprA binding. Similar results were obtained with DsrA. The results
      indicate that the full upstream leader sequence of rpoS mRNA influences Hfq
      facilitated annealing of RprA and DsrA and is likely to be involved in its
      regulation.

PMID- 18826257
TI  - Protein phosphatase-1 is targeted to DNA polymerase delta via an interaction with
      the p68 subunit.
AB  - Protein phosphatase-1 (PP1) is a Ser/Thr protein phosphatase that participates in
      the phosphorylation/dephosphorylation regulation of a diverse range of cellular
      processes. The PP1 catalytic subunit (PP1) achieves this by its ability to
      interact with many targeting subunits such that PP1 activity is thereby specified
      against phosphoprotein substrates in the microvicinity of its targeting subunit.
      DNA polymerase delta (Pol delta) is a key enzyme in mammalian chromosomal
      replication. It consists of four subunits, p125, p50, p68, and p12. We identify
      p68 as a novel PP1 targeting subunit. PP1 was shown to associate with human DNA
      polymerase delta by affinity chromatography and coimmunoprecipitation assays from
      mammalian cell lysates and in vitro by pull-down assays. The binding domain for
      PP1 was identified as the sequence KRVAL, a variant of the canonical RVxF PP1
      binding motif. These studies provide the first evidence for the targeting of PP1
      to DNA polymerase delta. We also show that CK2 phosphorylates the Pol delta p125,
      p68, and p12 subunits and that these phosphorylated subunits are substrates for
      PP1. These findings identify a new role for p68 as a PP1 targeting subunit that
      implicates PP1 in the dephosphorylation of Pol delta. Our findings also show that
      CK2 is a strong candidate for the protein kinase involved in the in vivo
      phosphorylation of p68.

PMID- 18826258
TI  - Diverse cell signaling events modulated by perlecan.
AB  - Perlecan is a ubiquitous pericellular proteoglycan ideally placed to mediate cell
      signaling events controlling migration, proliferation, and differentiation. Its
      control of growth factor signaling usually involves interactions with the heparan
      sulfate chains covalently coupled to the protein core's N-terminus. However, this
      modular protein core also binds with relatively high affinity to a number of
      growth factors and surface receptors, thereby stabilizing cell-matrix links. This
      review will focus on perlecan-growth factor interactions and describe recent
      advances in our understanding of this highly conserved proteoglycan during
      development, cancer growth, and angiogenesis. The pro-angiogenic capacities of
      perlecan that involve proliferative and migratory signals in response to bound
      growth factors will be explored, as well as the anti-angiogenic signals resulting
      from interactions between the C-terminal domain known as endorepellin and
      integrins that control adhesion of cells to the extracellular matrix. These two
      somewhat diametrically opposed roles will be discussed in light of new data
      emerging from various fields which converge on perlecan as a key regulator of
      cell growth and angiogenesis.

PMID- 18826259
TI  - Intermediate in the O-O bond cleavage reaction of an extradiol dioxygenase.
AB  - The reactive oxy intermediate of the catalytic cycle of extradiol aromatic ring
      cleaving dioxygenases is formed by binding the catecholic substrate and O2 in
      adjacent ligand positions of the active site metal [usually Fe(II)]. This
      intermediate and the following Fe(II)-alkylperoxo intermediate resulting from
      oxygen attack on the substrate have been previously characterized in a crystal of
      homoprotocatechuate 2,3-dioxygenase (HPCD). Here a subsequent intermediate in
      which the O-O bond is broken to yield a gem diol species is structurally
      characterized. This new intermediate is stabilized in the crystal by using the
      alternative substrate, 4-sulfonylcatechol, and the Glu323Leu variant of HPCD,
      which alters the crystal packing.

PMID- 18826260
TI  - A 106-kDa aminopeptidase is a putative receptor for Bacillus thuringiensis
      Cry11Ba toxin in the mosquito Anopheles gambiae.
AB  - Bacillus thuringiensis (Bt) insecticidal toxins bind to receptors on midgut
      epithelial cells of susceptible insects, and binding triggers biochemical events
      that lead to insect mortality. Recently, a 100-kDa aminopeptidase N (APN) was
      isolated from brush border membrane vesicles (BBMV) of Anopheles quadrimaculatus
      and shown to bind Cry11Ba toxin with surface plasmon resonance (SPR) detection
      [Abdullah et al. (2006) BMC Biochem. 7, 16]. In our study, a 106-kDa APN, called
      AgAPN2, released by phosphatidylinositol-specific phospholipase C (PI-PLC) from
      Anopheles gambiae BBMV was extracted by Cry11Ba bound to beads. The AgAPN2 cDNA
      was cloned, and analysis of the predicted AgAPN2 protein revealed a zinc-binding
      motif (HEIAH), three potential N-glycosylation sites, and a predicted
      glycosylphosphatidylinositol (GPI) anchor site. Immunohistochemistry localized
      AgAPN2 to the microvilli of the posterior midgut. A 70-kDa fragment of the 106
      kDa APN was expressed in Escherichia coli. When purified, it competitively
      displaced 125I-Cry11Ba binding to An. gambiae BBMV and bound Cry11Ba on dot blot
      and microtiter plate binding assays with a calculated K d of 6.4 nM. Notably,
      this truncated peptide inhibited Cry11Ba toxicity to An. gambiae larvae. These
      results are evidence that the 106-kDa GPI-anchored APN is a specific binding
      protein, and a putative midgut receptor, for Bt Cry11Ba toxin.

PMID- 18826261
TI  - Ceramide-enriched membrane domains in red blood cells and the mechanism of
      sphingomyelinase-induced hot-cold hemolysis.
AB  - Hot-cold hemolysis is the phenomenon whereby red blood cells, preincubated at 37
      degrees C in the presence of certain agents, undergo rapid hemolysis when
      transferred to 4 degrees C. The mechanism of this phenomenon is not understood.
      PlcHR 2, a phospholipase C/sphingomyelinase from Pseudomonas aeruginosa, that is
      the prototype of a new phosphatase superfamily, induces hot-cold hemolysis. We
      found that the sphingomyelinase, but not the phospholipase C activity, is
      essential for hot-cold hemolysis because the phenomenon occurs not only in human
      erythrocytes that contain both phosphatidylcholine (PC) and sphingomyelin (SM)
      but also in goat erythrocytes, which lack PC. However, in horse erythrocytes,
      with a large proportion of PC and almost no SM, hot-cold hemolysis induced by
      PlcHR 2 is not observed. Fluorescence microscopy observations confirm the
      formation of ceramide-enriched domains as a result of PlcHR 2 activity. After
      cooling down to 4 degrees C, the erythrocyte ghost membranes arising from
      hemolysis contain large, ceramide-rich domains. We suggest that formation of
      these rigid domains in the originally flexible cell makes it fragile, thus highly
      susceptible to hemolysis. We also interpret the slow hemolysis observed at 37
      degrees C as a phenomenon of gradual release of aqueous contents, induced by the
      sphingomyelinase activity, as described by Ruiz-Arguello et al. [(1996) J. Biol.
      Chem. 271, 26616]. These hypotheses are supported by the fact that ceramidase,
      which is known to facilitate slow hemolysis at 37 degrees C, actually hinders hot
      cold hemolysis. Differential scanning calorimetry of erytrocyte membranes treated
      with PlcHR 2 demonstrates the presence of ceramide-rich domains that are rigid at
      4 degrees C but fluid at 37 degrees C. Ceramidase treatment causes the
      disapperance of the calorimetric signal assigned to ceramide-rich domains.
      Finally, in liposomes composed of SM, PC, and cholesterol, which exhibit slow
      release of aqueous contents at 37 degrees C, addition of 10 mol % ceramide and
      transfer to 4 degrees C cause a large increase in the rate of solute efflux.

PMID- 18826262
TI  - Collective rotations of ferroelectric liquid crystals at the air/water interface.
AB  - We study the Langmuir monolayers of four different ferroelectric liquid crystals
      on water surface. Two of them are attached to water surface by their polar
      groups, and the chiral groups, at the opposite ends of the elongated molecules,
      remain well above the interface. The other two ferroelectrics have both groups
      (polar and chiral) at close proximity, and therefore the chiral group is also
      attached to the surface or even submerged in water. We demonstrate that only when
      the chiral group of the ferroelectric liquid crystal in Langmuir monolayer is not
      attached to the interface and stays in the air does the system exhibit the
      collective rotations induced by evaporation of water (described for the first
      time by: Tabe, Y.; Yokoyama, H. Nat. Mater. 2003, 2, 806). The isotherms of
      surface pressure and surface potential versus molecular area of four compounds
      were measured with simultaneous observations using Brewster angle microscopy.
      Experimental data of the compression isotherms are described with a van der Waals
      model with very good accuracy, and the fitted parameters were used for
      calculations of compressibility coefficients for different phases found in the
      compounds under investigations. The ability of the two compounds for rotation and
      the disability of the two others is discussed in a context of thermodynamic
      properties of the monolayers.

PMID- 18826263
TI  - In situ detection of live cancer cells by using bioprobes based on Au
      nanoparticles.
AB  - We fabricate the high-performance probes based on Au nanoparticles (AuNP) for
      detection of live cancer cell. AuNP were synthesized with narrow sized
      distribution (ca. 10 nm) by Au salt reduction method and deposited onto the
      aminated substrate as a cross-linker and hot spot. Herein, AuNP has enabled the
      easy and efficient immobilization of the antibody (Cetuximab), which can
      selectively interact with epidermal growth factor receptor (EGFR) on the surface
      of epidermal cancer, as detecting moiety onto the AuNP-deposited substrate
      without nanolithography process. After conjugation of Cetuximab with AuNP
      deposited substrate, Cetuximab-conjugated probe as a live cancer cell detector
      (LCCD) could detect EGFR-highexpressed A431 cells related to epithelial cancer
      with 54-times larger specificity and sensitivity in comparison with EGFR
      deficient MCF7 cells. This implies that AuNP-based probes demonstrate abundant
      potentials for detection and separation of small biomolecules, cells and other
      chemicals.

PMID- 18826264
TI  - Cellular delivery and biological activity of antisense oligonucleotides
      conjugated to a targeted protein carrier.
AB  - Targeted delivery can potentially improve the pharmacological effects of
      antisense and siRNA oligonucleotides. Here, we describe a novel bioconjugation
      approach to the delivery of splice-shifting antisense oligonucleotides (SSOs).
      The SSOs are linked to albumin via reversible S-S bonds. The albumin is also
      conjugated with poly(ethylene glycol) (PEG) chains that terminate in an RGD
      ligand that selectively binds the alphavbeta3 integrin. As a test system, we
      utilized human melanoma cells that express the alphavbeta3 integrin and that also
      contain a luciferase reporter gene that can be induced by delivery of SSOs to the
      cell nucleus. The RGD-PEG-SSO-albumin conjugates were endocytosed by the cells in
      an RGD-dependent manner; using confocal fluorescence microscopy, evidence was
      obtained that the SSOs accumulate in the nucleus. The conjugates were able to
      robustly induce luciferase expression at concentrations in the 25-200 nM range.
      At these levels, little short-term or long-term toxicity was observed. Thus, the
      RGD-PEG-albumin conjugates may provide an effective tool for targeted delivery of
      oligonucleotides to certain cells and tissues.

PMID- 18826265
TI  - Mechanism of H2 production by the [FeFe]H subcluster of di-iron hydrogenases:
      implications for abiotic catalysts.
AB  - To explore the possibility that the active center of the di-iron hydrogenases,
      the [FeFe] H subcluster, can serve by itself as an efficient hydrogen-producing
      catalyst, we perform comprehensive calculations of the catalytic properties of
      the subcluster in vacuo using first principles density functional theory. For
      completeness, we examine all nine possible geometrical isomers of the Fe(II)Fe(I)
      active-ready state and report in detail on the relevant ones that lead to the
      production of H 2. These calculations, carried out at the generalized gradient
      approximation level, indicate that the most efficient catalytic site in the
      isolated [FeFe] H subcluster is the Fe d center distal (d) to the [4Fe-4S] H
      cluster; the other iron center site, the proximal Fe p, also considered in this
      study, has much higher energy barriers. The pathways with the most favorable
      kinetics (lowest energy barrier to reaction) proceed along configurations with a
      CO ligand in a bridging position. The most favorable of these CO-bridging
      pathways start from isomers where the distal CN (-) ligand is in up position, the
      vacancy V in down position, and the remaining distal CO is either cis or trans
      with respect to the proximal CO. These isomers, not observed in the available
      enzyme X-ray structures, are only marginally less stable than the most stable
      nonbridging Fe d-CO-terminal isomer. Our calculations indicate that this CO
      bridging CN-up isomer has a small barrier to production of H 2 that is compatible
      with the observed rate for the enzyme. These results suggest that catalysis of H
      2 production could proceed on this stereochemically modified [FeFe] H subcluster
      alone, thus offering a promising target for functional bioinspired catalyst
      design.

PMID- 18826266
TI  - Comparison of the hydration and diffusion of protons in perfluorosulfonic acid
      membranes with molecular dynamics simulations. scui@utk.edu.
AB  - Classical molecular dynamics (MD) simulations were performed to determine the
      hydrated morphology and hydronium ion diffusion coefficients in two different
      perfluorosulfonic acid (PFSA) membranes as functions of water content. The
      structural and transport properties of 1143 equivalent weight (EW) Nafion, with
      its relatively long perfluoroether side chains, are compared to the short-side
      chain (SSC) PFSA ionomer at an EW of 977. The separation of the side chains was
      kept uniform in both ionomers consisting of -(CF 2) 15- units in the backbone,
      and the degree of hydration was varied from 5 to 20 weight % water. The MD
      simulations indicated that the distribution of water clusters is more dispersed
      in the SSC ionomer, which leads to a more connected water-channel network at the
      low water contents. This suggests that the SSC ionomer may be more inclined to
      form sample-spanning aqueous domains through which transport of water and protons
      may occur. The diffusion coefficients for both hydronium ions and water molecules
      were calculated at hydration levels of 4.4, 6.4, 9.6, and 12.8 H 2O/SO 3H for
      each ionomer. When compared to experimental proton diffusion coefficients, this
      suggests that as the water content is increased the contribution of proton
      hopping to the overall proton diffusion increases.

PMID- 18826267
TI  - Scaling law of poly(ethylene oxide) chain permeation through a nanoporous wall.
AB  - This paper presents a study of the permeation of poly(ethylene oxide) (PEO)
      chains through the nanoporous wall of hollow polymeric capsules prepared by self
      assembly of polyelectrolytes. We employ the method of pulsed field gradient (PFG)
      NMR diffusion to distinguish chains in different sites, i.e., in the capsule
      interior and free chains in the dispersion, by their respective diffusion
      coefficient. From a variation of the observation time, the time scale of the
      molecular exchange between both sites and thus the permeation rate constant is
      extracted from a two-site exchange model. Permeation rate constants show two
      different regimes with a different dependence on chain length. This suggests a
      transition between two different mechanisms of permeation as the molecular weight
      is increased. In either regime, the permeation time can be described by a scaling
      law tau approximately N (b) , with b = (4)/ 3 for short chains and b = (1)/ 3 for
      long chains. We discuss these exponents, which clearly differ from the
      theoretical predictions for chain translocation.

PMID- 18826268
TI  - Raman spectroscopic study on the coordination behavior of rare earth ions in N
      methylacetamide.
AB  - The coordination behavior of rare earth (Ln (3+)) ions in N-methylacetamide (NMA)
      solution has been investigated at room temperature by Raman spectroscopy. The
      behavior of the symmetric Raman Ln-Cl stretching (nu Ln-Cl) band, and amide I (nu
      AI), and III (nu AIII) bands of NMA with the rare earth series is discussed in
      conjunction with the change in the coordination structure occurring in the middle
      of the rare earth series. A competition for a coordination equilibria between a
      Cl (-) ion and an NMA molecule from the rare earth chloride-NMA complex might
      occur in the middle rare earth region. It is demonstrated that the change in the
      coordination structure of Ln (3+) ions in NMA is due to an elimination of an NMA
      molecule.

PMID- 18826269
TI  - Fast stochastic librations and slow rotations of spin labeled stearic acids in a
      model phospholipid bilayer at cryogenic temperatures.
AB  - The spin label DOXYL (4,4-dimethyl-oxazolidine-1-oxyl) is a nitroxyl ring that
      can be attached rigidly at specific C-atom positions in the stearic acid. 5-DOXYL
      stearic acid and 16-DOXYL-stearic acid in 1-Palmitoyl-2-oleoyl- sn-glycero-3
      phosphocholine (POPC) lipid bilayers were studied using electron spin echo (ESE)
      spectroscopy at low temperatures. The anisotropy of ESE decay across the electron
      paramagnetic resonance (EPR) spectrum evidence that these spin labels participate
      in orientational motions at temperatures down to approximately 120 K for 5-DOXYL
      stearic acid and down to approximately 80 K for 16-DOXYL-stearic acid. Fast
      stochastic librations, with correlation time at the nanosecond time scale,
      manifest itself in a two-pulse ESE experiment. Stimulated three-pulse ESE
      experiment is sensitive to motions of ultrasmall amplitude, approximately 0.1-1
      degrees , developing at the microsecond time scale. The stimulated ESE decays
      were found to depend on the product of the two time delays of the pulse sequence.
      This fact may be described within a simple model of slow inertial rotations
      developing within this small range of angles with a rate of approximately 1 kHz.
      Both types of motion evidence the pronounced motional heterogeneity across the
      bilayer at cryogenic temperatures, with a remarkable increase of motion in the
      bilayer interior. The found low-temperature motions imply that hydrophobic parts
      of amphiphilic biomolecules may possess a noticeable mobility even at
      temperatures as low as approximately 100 K.

PMID- 18826270
TI  - Synthesis and characterization of new pyrrolidinium based protic ionic liquids.
      Good and superionic liquids.
AB  - New pyrrolidinium-cation-based protic acid ionic liquids (PILs) were prepared
      through a simple and atom-economic neutralization reactions between pyrrolidine
      and Bronsted acids, HX, where X is NO 3 (-), HSO 4 (-), HCOO (-), CH 3COO (-) or
      CF 3COO (-) and CH 3(CH 2) 6COO (-). The thermal properties, densities,
      electrochemical windows, temperature dependency of dynamic viscosity and ionic
      conductivity were measured for these PILs. All protonated pyrrolidinium salts
      studied here were liquid at room temperature and possess a high ionic
      conductivity (up to 56 mS cm (-1)) at room temperature. Pyrrolidinium based PILs
      have a relatively low cost, a low toxicity and exhibit a large electrochemical
      window as compared to other protic ionic liquids (up 3 V). Obtained results allow
      us to classify them according to a classical Walden diagram and to determinate
      their "Fragility". Pyrrolidinium based PILs are good or superionic liquids and
      shows extremely fragility. They have wide applicable perspectives for fuel cell
      devices, thermal transfer fluids, and acid-catalyzed reaction media as
      replacements of conventional inorganic acids.

PMID- 18826271
TI  - Solvent effect of alcohols at the L-edge of iron in solution: X-ray absorption
      and multiplet calculations.
AB  - The local electronic structure of Fe(III) and Fe(II) ions in different alcohol
      solutions (methanol, ethanol, propan-1-ol) is investigated by means of soft X-ray
      absorption spectroscopy at the iron L 2,3-edge. The experimental spectra are
      compared with ligand field multiplet simulations. The solvated Fe(III) complex is
      found to exhibit octahedral symmetry, while a tetragonal symmetry is observed for
      Fe(II). A decrease in the solvent polarity increases the charge transfer from the
      oxygen of the alcohol to the iron ions. This conclusion is supported by Hartree
      Fock calculations of the Mulliken charge distribution on the alcohols. A larger
      charge transfer is further observed from the solvent to Fe(III) compared to
      Fe(II), which is connected to the higher positive charge state of the former.
      Finally, iron ions in solution are found to prefer the high-spin configuration
      irrespective of their oxidation state.

PMID- 18826272
TI  - Temperature-controlled photosensitization properties of benzophenone-conjugated
      thermoresponsive copolymers.
AB  - We previously found that a copolymer, poly(NIPAM- co-BP), consisting of N
      isopropylacrylamide (NIPAM) and benzophenone (BP) units, behaves as a
      photosensitizer showing temperature-controlled oxygenation activity by singlet
      oxygen ( (1)O 2) in water ( J. Am. Chem. Soc. 2006, 128, 8751-8753 ). This
      polymer shows a heat-induced oxygenation enhancement at <20 degrees C, while
      showing suppression at >20 degrees C. This is driven by a heat-induced phase
      transition of the polymer from coil to micelle and then to globule state,
      controlling the stability and diffusion of (1)O 2 and the location of substrate.
      In the present work, effects of polymer concentration and BP content of the
      polymer on the oxygenation activity were studied at 5-35 degrees C. Increase in
      the polymer concentration leads to activity decrease at >20 degrees C due to
      strong polymer aggregation, suppressing incident light absorption of the BP
      units. With a decrease in BP content of the polymer, heat-induced oxygenation
      enhancement at <20 degrees C is more pronounced because formation of small size
      micelles accelerates (1)O 2 oxygenation. The obtained findings reveal that the
      polymer with low BP content, when used at high concentration, shows clear-cut off
      on- off activity change against the temperature window: very low activity at <5
      degrees C and >25 degrees C, and very high activity at middle temperature range.

PMID- 18826273
TI  - Chemical potentials in aqueous solutions of some ionic liquids with the 1-ethyl-3
      methylimidazolium cation.
AB  - We determined the vapor pressures of aqueous solutions of 1-ethyl-3
      methylimidazolium ([C 2mim])-based ionic liquids (IL) with counteranions,
      tetrafluoroborate (BF 4 (-)), trifluoromethanesulfonate (OTF (-)), and iodide (I
      (-)). Because in literature the evidence is accumulating and pointing to the fact
      that ionic liquid ions do not dissociate in aqueous media for the most of the
      concentration range, we analyzed the vapor pressure data on the basis of binary
      mixture, and the excess chemical potentials of each component were calculated.
      From these, the intermolecular interactions in terms of excess chemical potential
      and hence the concentration fluctuations were evaluated. Though any further
      discussion into the mixing schemes of the mixture awaits the excess partial molar
      enthalpy and hence the excess partial molar entropy data, the net interaction in
      terms of excess chemical potential indicates that the affinity of each IL is
      ranked in the descending order [C 2mim]I > [C 2mim]OTF > [C 2mim]BF 4. This is
      consistent with our earlier findings that [C 2mim] (+) is modestly amphiphilic
      with almost equal hydrophobicity and hydrophilicity, I (-) is a hydrophile, and
      OTF (-) is amphiphilic, and BF 4 (-) is believed to be strongly hydrophobic.

PMID- 18826274
TI  - Synthesis and characterization of a new polysaccharide-graft-polymethacrylate
      copolymer for three-dimensional hybrid hydrogels.
AB  - Hybrid materials constituted by hydrophobic and hydrophilic biocompatible
      macromolecules are useful for biomedical applications. In this context, a well
      known acrylic monomer (methyl methacrylate) was polymerized and grafted onto the
      polysaccharide dextran by the use of ceric ammonium nitrate as a redox initiator
      in aqueous nitric acid medium. The effects of concentrations of dextran, acrylic
      monomer, and ceric ions on the copolymerization yields were investigated in
      detail. The obtained polymers were studied by solubility measurements, Fourier
      transform infrared spectrometry, (13)C nuclear magnetic resonance spectroscopy,
      and viscosimetric analysis. Interestingly, we found conditions to form
      transparent and homogeneous thin films or 3D structures with hybrid properties.
      Indeed, the copolymer, but not dextran or PMMA, could be dissolved in water/THF
      (20/80 v/v). The thermomechanical properties of the resulting copolymer analyzed
      by differential scanning calorimetry and dynamic mechanical analysis showed the
      occurrence of a single glass-transition temperature and a marked difference with
      the two homopolymers. The cytocompatibility of the copolymer with human
      endothelial cells was evidenced by the normal cell adhesion, proliferation, and
      morphology after 5 days in culture on these gels. In conclusion, this type of
      copolymer with hybrid properties of two biocompatible macromolecules could be of
      great interest as a 3D scaffold or for coating in biomedical applications.

PMID- 18826275
TI  - Cell response to RGD density in cross-linked artificial extracellular matrix
      protein films.
AB  - This study examines the adhesion, spreading, and migration of human umbilical
      vein endothelial cells on cross-linked films of artificial extracellular matrix
      (aECM) proteins. The aECM proteins described here were designed for application
      in small-diameter grafts and are composed of elastin-like structural repeats and
      fibronectin cell-binding domains. aECM-RGD contains the RGD sequence derived from
      fibronectin; the negative control protein aECM-RDG contains a scrambled cell
      binding domain. The covalent attachment of poly(ethylene glycol) (PEG) to aECM
      substrates reduced nonspecific cell adhesion to aECM-RDG-PEG but did not preclude
      sequence-specific adhesion of endothelial cells to aECM-RGD-PEG. Variation in
      ligand density was accomplished by the mixing of aECM-RGD-PEG and aECM-RDG-PEG
      prior to cross-linking. Increasing the density of RGD domains in cross-linked
      films resulted in more robust cell adhesion and spreading but did not affect cell
      migration speed. Control of cell-binding domain density in aECM proteins can thus
      be used to modulate cell adhesion and spreading and will serve as an important
      design tool as these materials are further developed for use in surgery, tissue
      engineering, and regenerative medicine.

PMID- 18826276
TI  - Rhabdastrellins A-F, isomalabaricane triterpenes from the marine sponge
      Rhabdastrella aff. distincta.
AB  - Chemical examination of the marine sponge Rhabdastrella aff. distincta resulted
      in the isolation of six new isomalabaricane triterpenes, rhabdastrellins A-F (1
      6), which were present as minor components, along with stellettins L and M. Their
      structures were elucidated on the basis of extensive spectroscopic data analyses
      and comparison with spectroscopic data of known analogues. The cytotoxicity of
      compounds 1-6 against a small panel of human tumor cell lines was also evaluated.

PMID- 18826277
TI  - Antiproliferative triterpenes from Melaleuca ericifolia.
AB  - Three new 28-norlupane triterpenes, 28-norlup-20(29)-en-3beta-hydroxy-17beta
      hydroperoxide (1), 28-norlup-20(29)-en-3beta-hydroxy-17alpha-hydroperoxide (2),
      and 20 S-17beta,29-epoxy-28-norlupan-3beta-ol (3), were isolated from the leaves
      of Melaleuca ericifolia along with eight known pentacyclic triterpenes. The
      structures of the new compounds were elucidated by spectroscopic methods
      including 1D and 2D NMR spectroscopy and mass spectrometry. The isolated
      triterpenes were evaluated for antiproliferative activity against the malignant
      +SA mammary epithelial cell line.

PMID- 18826278
TI  - Tyrianthinic acids from Ipomoea tyrianthina and their antimycobacterial activity,
      cytotoxicity, and effects on the central nervous system.
AB  - Four new partially acylated tetrasaccharides of 11-hydroxyhexadecanoic acid (1-4)
      were isolated from a methanolic extract of Ipomoea tyrianthina. The structures of
      these compounds were elucidated by spectroscopic and chemical methods. The resin
      glycoside composition of I. tyrianthina varied with the location of growth in
      Mexico. Compounds 1-4 showed antimycobacterial activity, were cytotoxic against
      the KB cell line, and, in a mouse model, exhibited potentiation of hypnosis
      induced by pentobarbital, protected against seizures induced by
      pentylenetetrazole, and released GABA and glutamic acid.

PMID- 18826279
TI  - Asymmetric homologation of ketones. A new entry to orthogonally protected (2R,4R)
      piperidine-2,4-dicarboxylic acid.
AB  - A new conformationally constrained analogue of glutamic acid has been synthesized
      efficiently in seven steps from a chiral 2-alkyl-4-piperidone. The synthesis is
      based on (a) the unprecedented asymmetric one-carbon homologation of the ketone
      controlled by the size of the N-substituent and (b) the appropriate manipulation
      of substituents at positions 2 and 4 of the piperidine ring, a step that involves
      two independent oxidation processes.

PMID- 18826280
TI  - Regio- and stereochemistry of [2 + 2] photocycloadditions of imines to alkenes: a
      computational and experimental study.
AB  - The [2 + 2] photocycloaddition of isoxazolines to alkenes has been studied by
      means of CASPT2/6-31G*//CASSCF/6-31G*. The reaction outcome is influenced by the
      relative ratio of imine deactivation and photocycloaddition. Analysis of the
      conical intersection points involved in the photoreaction shows that fast
      deactivation is prevented when an electron-withdrawing group is placed in any
      position that can affect the imine moiety. Computational data predict that the
      photoreaction will be regiospecific but without stereoselectivity. Furthermore,
      the favored regioisomer will be different for alkenes with electron-withdrawing
      or electron-releasing substituents. The results of a complementary experimental
      study correlate well with the computational data. Several conclusions included in
      the present work could prove useful for the generalization of the
      photocycloaddition of imines.

PMID- 18826281
TI  - Asymmetric synthesis of 8-aminoindolizidine from chiral 2-pyrroleimines.
AB  - 1-Allyl-2-pyrroleimines obtained from (S)-valinol and (S)-phenylglycinol
      underwent highly diastereoselective addition of allylmagnesium chloride, used in
      excess amounts, to give the corresponding secondary amines with concomitant allyl
      to (Z)-1-propenyl isomerization of the 1-pyrrole substituent. Transformation of
      the 2-amino alcohol moiety to an oxazolidinone, or its cleavage and subsequent N
      protection, followed by ring-closing metathesis of the two alkene groups gave the
      unsaturated bicyclic compound. Full hydrogenation of the alkene function and the
      aromatic rings afforded the indolizidine derivative as a mixture of two or three
      diastereomers with a ratio which was dependent on the nature of both the N
      substituent and the catalyst. The two prevalent diastereomers were isolated, and
      their configuration was determined by X-ray crystallographic analysis.

PMID- 18826282
TI  - Fast, acid-free, and selective lactamization of lactones in ionic liquids.
AB  - A fast and acid-free one-pot 0.2-30 mmol microwave methodology for direct ionic
      liquid-mediated preparation of lactams from lactones and primary amines has been
      developed. The protocol was investigated with a wide range of primary amines and
      a handful of lactones, including substrates with acid-sensitive substituents.
      Both gamma-lactams and delta-lactams were, despite the complete absence of a
      Bronsted acid, obtained in useful to excellent yields after only 35 min of
      microwave processing.

PMID- 18826283
TI  - Crucial role of N...Si interactions in the solid-state coloration of
      disilylazobenzenes.
AB  - 2,2'-Bis(fluorodiphenylsilyl)azobenzenes bearing two methyl and butyl groups at
      the 4- and 4'-positions were synthesized, and their X-ray crystallographic
      analyses revealed that they have tetracoordinated and pentacoordinated silicon
      atoms, respectively. Although the two compounds showed almost the same spectra in
      solution, the reflectance spectra of the solid revealed that the pentacoordinated
      state had a weaker absorbance in the long-wavelength region compared with that of
      the tetracoordinated state, which is ascribed to the shift of the n-pi*
      transition. This difference in the absorptions due to the n-pi* transition
      drastically affects the color of the azobenzenes: the color of the
      pentacoordinated state becomes apparently paler than that of the tetracoordinated
      state.

PMID- 18826284
TI  - Site-specific fluorescent labeling approaches for naringenin, an essential
      flavonone in plant nitrogen-fixation signaling pathways.
AB  - In search of an appropriate position for the fluorescent labeling, six chemically
      available positions of the flavonone core of naringenin have been examined. A
      number of azido-containing naringenin derivatives were accordingly prepared in
      various site-specific fashions, and the mild Cu(I)-catalyzed Huisgen 1,3-dipolar
      cycloaddition successfully served as the common "Click" labeling tool in the
      final steps. On the basis of the biological activities of the first batch of
      labeled compounds, further optimization at the C-6 position of naringenin finally
      afforded naringenin-flu (27), which acquired 20% of the potency of naringenin and
      presented good optical properties. Entry of naringenin-flu into living Rhizobium
      cells was demonstrated by in vitro fluorescent imaging experiments.

PMID- 18826285
TI  - Ring-opening reactions of difluoro(methylene)cyclopropanes with halogens and
      amines.
AB  - The distal and proximal bond of difluoro(methylene)cyclopropanes (F2MCPs) could
      be cleaved, respectively, under different conditions to give the corresponding
      ring-opening products. The reaction mechanisms are discussed.

PMID- 18826286
TI  - A computational study of chlorocarbene additions to cyclooctyne.
AB  - Dichloro- and phenylchlorocarbene (CCl2 and PhCCl) add to cyclooctyne via a
      barrierless process (MP2/6-311+G*, B3LYP/6-311+G*, B3LYP/6-31G*) to yield the
      expected corresponding cyclopropene adducts. A three-dimensional potential energy
      surface (PES) for CCl2 addition to cyclooctyne (B3LYP/6-31G*) shows the formation
      of the cyclopropene product and also possible formation of a vinylcarbene.
      Residing in a shallow energy well, the vinylcarbene easily rearranges to the
      cyclopropene product, or to an exocyclic vinyl bicyclo[3.3.0]octane. Although the
      calculated three-dimensional PES indicates possible dynamic control of the
      cyclooctyne-chlorocarbene system through the putative formation of a vinylcarbene
      (in addition to the expected cyclopropene), additional calculations and
      preliminary experimental work show paths through the vinylcarbene to be unlikely.
      If the additions of chlorocarbenes to cyclooctyne are controlled by reaction
      dynamics, we predict that the vast majority of the reactions proceed via
      traditional carbene cycloaddition with only a very minor amount of products
      formed from the alternative pathway.

PMID- 18826287
TI  - Spinel LiMn2O4 nanorods as lithium ion battery cathodes.
AB  - Spinel LiMn2O4 is a low-cost, environmentally friendly, and highly abundant
      material for Li-ion battery cathodes. Here, we report the hydrothermal synthesis
      of single-crystalline beta-MnO2 nanorods and their chemical conversion into free
      standing single-crystalline LiMn2O4 nanorods using a simple solid-state reaction.
      The LiMn2O4 nanorods have an average diameter of 130 nm and length of 1.2 microm.
      Galvanostatic battery testing showed that LiMn2O4 nanorods have a high charge
      storage capacity at high power rates compared with commercially available
      powders. More than 85% of the initial charge storage capacity was maintained for
      over 100 cycles. The structural transformation studies showed that the Li ions
      intercalated into the cubic phase of the LiMn2O4 with a small change of lattice
      parameter, followed by the coexistence of two nearly identical cubic phases in
      the potential range of 3.5 to 4.3 V.

PMID- 18826288
TI  - Quantification of free-carrier absorption in silicon nanocrystals with an optical
      microcavity.
AB  - We present a highly sensitive and accurate microcavity-based technique to
      quantify the free-carrier absorption (FCA) cross-section of semiconductor quantum
      dot ensembles. The procedure is based on measuring the pump-intensity-dependent
      broadening of the whispering gallery modes (WGMs) of microdisk resonators. We
      have applied this technique to determine the FCA cross-section of Si nanocrystals
      (Si-ncs) in the visible-near-infrared wavelength range. Our procedure accounts
      for the size distribution effects by including the measured wavelength dependence
      of the excitation cross-section and the decay rate of photoexcited carriers in
      the analysis. By monitoring the WGM widths at various wavelengths in the 700-900
      nm wavelength range, we found that the FCA cross-section follows an approximately
      quadratic wavelength dependence. The magnitude of the FCA cross-section of Si
      nanocrystals was determined to be a factor of 7 higher than that in bulk Si. For
      this reason, these findings have important implications for the design of Si
      based lasers and all-optical switching devices in which FCA plays a critical
      role.

PMID- 18826289
TI  - Silicon nanowire transistors with a channel width of 4 nm fabricated by atomic
      force microscope nanolithography.
AB  - The emergence of an ultrasensitive sensor technology based on silicon nanowires
      requires both the fabrication of nanoscale diameter wires and the integration
      with microelectronic processes. Here we demonstrate an atomic force microscopy
      lithography that enables the reproducible fabrication of complex single
      crystalline silicon nanowire field-effect transistors with a high electrical
      performance. The nanowires have been carved from a silicon-on-insulator wafer by
      a combination of local oxidation processes with a force microscope and etching
      steps. We have fabricated and measured the electrical properties of a silicon
      nanowire transistor with a channel width of 4 nm. The flexibility of the
      nanofabrication process is illustrated by showing the electrical performance of
      two nanowire circuits with different geometries. The fabrication method is
      compatible with standard Si CMOS processing technologies and, therefore, can be
      used to develop a wide range of architectures and new microelectronic devices.

PMID- 18826290
TI  - Nanoparticle self-assembly on a DNA-scaffold written by single-molecule cut-and
      paste.
AB  - Self-assembly guided by molecular recognition has in the past been employed to
      assemble nanoparticle superstructures like hypercrystals or nanoparticle
      molecules. An alternative approach, the direct molecule-by-molecule assembly of
      nanoscale superstructures, was demonstrated recently. Here we present a hybrid
      approach where we first assemble a pattern of binding sites one-by-one at a
      surface and then allow different nanoparticles to attach by self-assembly. For
      this approach, biotin bearing DNA oligomers were picked up from a depot using a
      cDNA strand bound to an AFM tip. These units were deposited in the target area by
      hybridization, forming a recognition pattern on this surface. Fluorescent
      semiconductor nanoparticles conjugated with streptavidin were allowed to assemble
      on this scaffold and to form the final nanoparticle superstructures.

PMID- 18826291
TI  - Nanopatterned carbon films with engineered morphology by direct carbonization of
      UV-stabilized block copolymer films.
AB  - Nanopatterned thin carbon films were prepared by direct and expeditious
      carbonization of the block copolymer polystyrene- block-poly(2-vinylpyridine) (PS
      b-P2VP) without the necessity of slow heating to the process temperature and of
      addition of further carbon precursors. Carbonaceous films having an ordered "dots
      on-film" surface topology were obtained from reverse micelle monolayers. The
      regular nanoporous morphology of PS- b-P2VP films obtained by subjecting reverse
      micelle monolayers to swelling-induced surface reconstruction could likewise be
      transferred to carbon films thus characterized by ordered nanopit arrays.
      Stabilization of PS- b-P2VP by UV irradiation and the concurrent carbonization of
      both blocks were key to the conservation of the film topography. The approach
      reported here may enable the realization of a broad range of nanoscaled
      architectures for carbonaceous materials using a block copolymer ideally suited
      as a template because of the pronounced repulsion between its blocks and its
      capability to form highly ordered microdomain structures.

PMID- 18826292
TI  - Controlling S1/S0 decay and the balance between photochemistry and photostability
      in benzene: a direct quantum dynamics study.
AB  - In this work, we investigate general mechanistic principles that control reaction
      selectivity following S(1)/S(0) internal conversion in benzene. A systematic
      relationship is drawn between the varying topology of an extended seam of conical
      intersection and the balance between two competitive radiationless decay
      channels: photophysical (benzene reactant regeneration) and photochemical
      (prefulvene product formation). This is supported by a model quantum dynamics
      study, using a direct dynamics approach based on variational multiconfiguration
      Gaussian wavepackets, where initial excitation of specific vibrational modes is
      designed to generate dynamical pathways that reach selected targets regions of
      the seam. High-energy regions of the seam are found to be sloped and in favor of
      the photophysical channel, while lower-energy regions are peaked and give access
      to the photochemical channel. This changeover could in principle be exploited to
      define targets for optimal control, by exciting different combinations of
      specific vibronic levels in S(1), accessing different regions of the seam, and
      giving different products.

PMID- 18826293
TI  - Energetics and mechanisms of C-H bond activation by a doubly charged metal ion:
      guided ion beam and theoretical studies of Ta2+ + CH4.
AB  - A guided ion beam tandem mass spectrometer is used to study the kinetic-energy
      dependence of doubly charged atomic tantalum cations (Ta(2+)) reacting with CH4
      and CD4. As for the analogous singly charged system, the dehydrogenation reaction
      to form TaCH2(2+) + H2 is exothermic. The charge-transfer reaction to form Ta(+)
      + CH4(+) and the charge-separation reaction to form TaH(+) + CH3(+) are also
      observed at low energies in exothermic processes, as is a secondary reaction of
      TaCH2(2+) to form TaCH3(+) + CH3(+). At higher energies, other doubly charged
      products, TaC(2+) and TaCH3(2+), are observed, although no formation of TaH(2+)
      was observed. Modeling of the endothermic cross sections provides 0 K bond
      dissociation energies (in electronvolts) of D0(Ta(2+)-C) = 5.42 +/- 0.19 and
      D0(Ta(2+)-CH3) = 3.40 +/- 0.16. These experimental bond energies are in poor
      agreement with density functional calculations at the B3LYP/HW+/6-311++G(3df,3p)
      level of theory. However, the Ta(2+)-C bond energy is in good agreement with
      calculations at the QCISD(T) level of theory, and the Ta(2+)-CH3 bond energy is
      in good agreement with density functional calculations at the BHLYP level of
      theory. Theoretical calculations reveal the geometric and electronic structures
      of all product ions and are used to map the potential energy surface, which
      describes the mechanism of the reaction and key intermediates. Both experimental
      and theoretical results suggest that TaH(+), TaCH2(2+), and TaCH3(2+) are formed
      through a H-Ta(2+)-CH3 intermediate.

PMID- 18826294
TI  - Geometric and electronic structure of the aqueous Al(H2O)6(3+) complex.
AB  - The bonding environment of the aqueous Al(H2O)6(3+) complex was studied using X
      ray absorption near-edge structure (XANES) spectroscopy at the Al K-edge, with
      spectral interpretations based on density functional theory (DFT). Calculations
      for a highly symmetric complex (T(h) symmetry) indicate electron transitions into
      Al3 p-O 2s and Al3 p-O 2p antibonding orbitals, with a split O 2p contribution
      that appears to be due to a weak pi-interaction of the Al 3p orbitals with water
      ligands off-axis (equatorial) with respect to the Al 3p axis. Calculations were
      performed with several hypothetical structures to assess the effects of Al-O bond
      length, orientation of water ligands in the first coordination shell, and the
      presence of a second solvation shell on the XANES spectrum. Similar transitions
      were observed in all of these cases, but with further splitting on addition of 12
      solvation waters, inward tilting and random twisting of the water ligands, and
      nonuniform Al-O bond lengths. Although it was previously hypothesized that the
      broadness of the XANES spectrum for this complex is due to an asymmetric
      geometry, these results illustrate how an Al(H 2O)6(3+) geometry that is
      octahedral (O(h)) with respect to the Al-O6 core could produce the broad spectrum
      observed. Because geometric distortions would affect relative Al-O bond
      strengths, an understanding of the equilibrium Al(H2O)6(3+) geometry is
      prerequisite to a quantitative description of reaction chemistry, including
      acidity and ligand exchange.

PMID- 18826295
TI  - Modeling binding modes of alpha7 nicotinic acetylcholine receptor with ligands:
      the roles of Gln117 and other residues of the receptor in agonist binding.
AB  - Extensive molecular docking, molecular dynamics simulations, and binding free
      energy calculations have been performed to understand how alpha7-specific
      agonists of nicotinic acetylcholine receptor (nAChR), including AR-R17779 (1),
      GTS-21 (4), and 4-OH-GTS-21 (5), interact with the alpha7 receptor, leading to
      important new insights into the receptor-agonist binding. In particular, the
      cationic head of 4 and 5 has favorable hydrogen bonding and cation-pi
      interactions with residue Trp149. The computational results have also led us to
      better understand the roles of Gln117 and other residues in the receptor binding
      with agonists. The computational predictions are supported by data obtained from
      wet experimental tests. The new insights into the binding and structure-activity
      relationship obtained from this study should be valuable for future rational
      design of more potent and selective agonists of the alpha7 receptor.

PMID- 18826296
TI  - Bornyl- and isobornyl-Delta8-tetrahydrocannabinols: a novel class of
      cannabinergic ligands.
AB  - Structure-activity relationship studies of classical cannabinoid analogues have
      established that the C3 aliphatic side chain plays a pivotal role in determining
      cannabinergic potency. In earlier work, we provided evidence for the presence of
      subsites within the CB1 and CB2 cannabinoid receptor binding domains that can
      accommodate bulky conformationally defined substituents at the C3 alkyl side
      chain pharmacophore of classical cannabinoids. We have now extended this work
      with the synthesis of a series of Delta (8)-THC analogues in which bornyl
      substituents are introduced at the C3 position. Our results indicate that, for
      optimal interactions with both CB1 and CB2 receptors, the bornyl substituents
      need to be within close proximity of the tricyclic core of Delta (8)-THC and that
      the conformational space occupied by the C3 substituents influences CB1/CB2
      receptor subtype selectivity.

PMID- 18826297
TI  - Synthesis and structure-activity relationship studies of highly potent novel
      oxazolidinone antibacterials.
AB  - Novel antibacterial biaryl oxazolidinones bearing an aza-, an oxa-, or a
      thiabicyclo[3.1.0]hex-6-yl ring system were synthesized, and their in vitro
      antibacterial activity and structure-activity relationships (SAR) were evaluated.
      Most of the synthesized biaryl bicyclo[3.1.0]hex-6-yl oxazolidinones showed good
      antibacterial activity against the Gram-positive and -negative bacteria tested.
      Regarding SAR trends among the C-ring subtypes, the pyridyl ring was preferable
      to the phenyl ring. The results showed that the structural variety of the C-ring
      has a greater impact on antibacterial activity than that of the B-ring. A cyano
      group at the D-ring C-6 position plays an important role in the highly potent
      antibacterial activity.

PMID- 18826299
TI  - Conjugated chitosan as a novel platform for oral delivery of paclitaxel.
AB  - A new platform for oral delivery of paclitaxel (PTX) was developed through
      chemical conjugation of PTX to a low molecular weight chitosan (LMWC). The LMWC
      PTX conjugate contained approximately 12 wt % PTX and showed greatly enhanced
      water solubility (>1 mg/mL) as compared to native PTX. The conjugate showed
      comparable IC 50 values to that of the parent PTX against human cancer cell
      lines. The pharmacokinetic data revealed approximately 42% of bioavailability
      after oral administration of 5 mg PTX/kg of the conjugate. When the conjugate (10
      mg/kg based on PTX content) was administered orally to mice bearing xenograft or
      allograft tumors, the conjugate-treated group showed significant inhibition of
      tumor growth, which was comparable to that seen with PTX of the clinically
      available injected form, formulated in cremophor EL/ethanol (iv) but with much
      lower toxicity. Tracking I (125)-labeled conjugate showed that LMWC-PTX was
      likely to be absorbed mainly from the ileum and reach the blood as the intact
      conjugate.

PMID- 18826300
TI  - Impact of rpoS deletion on the proteome of Escherichia coli grown planktonically
      and as biofilm.
AB  - To investigate the role of rpoS in gene expression of Escherichia coli cells
      grown as biofilms, we compared the proteomes of a rpoS mutant and the wild-type
      strain. Experiments were performed on planktonic cells (in exponential or
      stationary growth phase) and biofilms developed on glass wool. Spot-by-spot
      comparison of gels obtained from biofilm and planktonic wild-type organisms
      showed that the intensity of between 22 and 30% of detected spots was affected by
      the growth mode, depending of the control used. Principal component analysis,
      used to interpret the variations in protein spot densities, discriminated
      exponential-phase cells (wild-type and mutant) from the other incubation
      conditions and secondarily 72-old cultures. The statistical analysis demonstrated
      that the rpoS mutation did not significantly modify the proteome of exponential
      growth phase cells, the differences involving only 3% of the proteome. However,
      increasing the incubation time from 8 to 72 h noticeably increased the number of
      changed proteins. A cluster analysis showed that RpoS plays a role in the special
      nature of the gene expression of biofilm cells but lower than in stationary-phase
      bacteria. We identified 35 rpoS-regulated proteins that were already or not
      described as controlled by this sigma factor. For some of them, the mode of
      regulation by RpoS was obviously dependent on the culture condition (planktonic
      vs biofilm).

PMID- 18826301
TI  - Approved drug mimics of short peptide ligands from protein interaction motifs.
AB  - Most biological functions are regulated through complex networks of transient
      protein interactions, and, thus, finding effective ways to modulate them would
      represent an important step towards defining the next generation of drugs. In
      this study, we set out to determine if existing approved drugs may represent a
      good source of compounds from which initial lead inhibitors of protein-protein
      interactions mediated by short peptide regions may be drawn. Peptide structures
      were defined in terms of pharmacophores and searched against U.S. Food and Drug
      Administration (FDA)-approved drugs to identify similar compounds. The top
      ranking matches (using a score that corrects root-mean-square deviation (rmsd)
      for the number of matched pharmacophores and for the number of drug rotatable
      bonds) included a number of nuclear receptor ligands that matched allosterically
      to the corepressor binding site of peroxisome proliferator-activated receptor
      alpha (PPARalpha). The top ranking drug matches were docked to the peptide
      binding site using AUTODOCK. The majority of the top-ranking matches showed a
      negative estimated free energy change upon binding that is comparable to, or
      greater than, that of the original peptide. We conclude that the usage of certain
      approved drugs may represent a useful strategy in inhibiting specific protein
      protein interactions. Such a strategy may benefit from the increased likelihood
      that developed compounds might have favorable bioactivity and safety profiles in
      clinical use.

PMID- 18826302
TI  - Encapsulation of uncharged water-insoluble organic substance in polymeric
      membrane capsules via layer-by-layer approach.
AB  - We report a general and versatile method for the encapsulation of electrically
      uncharged organic substance in polymeric capsules by using a layer-by-layer (LbL)
      approach. Electrical charge was induced on the surface of pyrene (uncharged
      organic substance) with an amphiphilic surfactant (sodium dodecyl sulfate, SDS)
      by micellar solubilization. The SDS micellar solution of pyrene in water was then
      deposited on a flat substrate as well as colloidal particles with chitosan as an
      oppositely charged polyelectrolyte. Pyrene was used as a model drug because it
      displayed intrinsic fluorescence that allowed us to monitor LbL growth by
      fluorescence and under confocal laser scanning microscopy (CLSM). To examine the
      proof of concept, multilayers were coated on the planar support by the LbL
      method. UV-vis spectroscopy showed regular growth of each layer deposited. Thin
      film formation was evidenced by scanning electron microscopy. The LbL method was
      extended to particles where fluorescence spectroscopy revealed LbL growth and
      transmission electron microscopy (TEM) provided evidence of particle coating. The
      quantification of dye in each deposited layer further proved LbL growth. The
      removal of sacrificial core provided thin capsules. The capsules were
      characterized by TEM and CLSM. The capsules showed potential as a drug delivery
      system, which is suggested by the slow release of entrapped dye by concentration
      dependent diffusion in isotonic saline solution. The kinetics of desorption of
      pyrene from this thin film was modeled by a pseudo-second-order model.

PMID- 18826303
TI  - Comment on "a theoretical investigation of the interactions between water
      molecules and ionic liquids".

PMID- 18826304
TI  - Pseudomorphic transformation of highly ordered mesoporous Co3O4 to CoO via
      reduction with glycerol.
AB  - In this report, we describe the exploration of possibilities for a pseudomorphic
      reduction of ordered mesoporous metal oxides by high temperature treatment with
      glycerol, which was most thoroughly studied as an example of the reaction of
      Co3O4 to CoO. It was found that the glycerol process is a gentle reduction
      procedure, which maintains the framework topology on the mesoscale while changing
      the oxidation state and the structure at the atomic scale.

PMID- 18826305
TI  - Strategy for employing unstabilized nucleophiles in palladium-catalyzed
      asymmetric allylic alkylations.
AB  - We report a strategy for the employment of highly unstabilized anions in
      palladium-catalyzed asymmetric allylic alkylations (AAA). The "hard" 2
      methylpyridyl nucleophiles studied are first reacted in situ with BF3.OEt2;
      subsequent deprotonation of the resulting complexes with LiHMDS affords "soft"
      anions that are competent nucleophiles in AAA reactions. The reaction is
      selective for the 2-position of methylpyridines and tolerates bulky aryl and
      alkyl substitution at the 3-, 4-, and 5-positions. Investigations into the
      reaction mechanism demonstrate that the configuration of the allylic stereocenter
      is retained, consistent with the canonical outer sphere mechanism invoked for
      palladium-catalyzed allylic substitution processes of stabilized anions.

PMID- 18826306
TI  - Molecular tweezers for hydrogen: synthesis, characterization, and reactivity.
AB  - The first ansa-aminoborane N-TMPN-CH2C6H4B(C6F5)2 (where TMPNH is 2,2,6,6
      tetramethylpiperidinyl) which is able to reversibly activate H2 through an
      intramolecular mechanism is synthesized. This new substance makes use of the
      concept of molecular tweezers where the active N and B centers are located close
      to each other so that one H2 molecule can fit in this void and be activated.
      Because of the fixed geometry of this ansa-ammonium-borate it forms a short N
      H...H-B dihydrogen bond of 1.78 A as determined by X-ray analysis. Therefore, the
      bound hydrogen can be released above 100 degrees C. In addition, the short H...H
      contact and the N-H...H (154 degrees) and B-H...H (125 degrees) angles show that
      the dihydrogen interaction in N-TMPNH-CH2C6H4BH(C6F5)2 is partially covalent in
      nature. As a basis for discussing the mechanism, quantum chemical calculations
      are performed and it is found that the energy needed for splitting H2 can arise
      from the Coulomb attraction between the resulting ionic fragments, or "Coulomb
      pays for Heitler-London". The air- and moisture-stable N-TMPNH-CH2C6H4BH(C6F5)2
      is employed in the catalytic reduction of nonsterically demanding imines and
      enamines under mild conditions (110 degrees C and 2 atm of H2) to give the
      corresponding amines in high yields.

PMID- 18826307
TI  - Femtosecond time-resolved optical and Raman spectroscopy of photoinduced spin
      crossover: temporal resolution of low-to-high spin optical switching.
AB  - A combination of femtosecond electronic absorption and stimulated Raman
      spectroscopies has been employed to determine the kinetics associated with low
      spin to high-spin conversion following charge-transfer excitation of a FeII spin
      crossover system in solution. A time constant of tau = 190 +/- 50 fs for the
      formation of the 5T2 ligand-field state was assigned based on the establishment
      of two isosbestic points in the ultraviolet in conjunction with changes in ligand
      stretching frequencies and Raman scattering amplitudes; additional dynamics
      observed in both the electronic and vibrational spectra further indicate that
      vibrational relaxation in the high-spin state occurs with a time constant of ca.
      10 ps. The results set an important precedent for extremely rapid, formally
      forbidden (DeltaS = 2) nonradiative relaxation as well as defining the time scale
      for intramolecular optical switching between two electronic states possessing
      vastly different spectroscopic, geometric, and magnetic properties.

PMID- 18826308
TI  - Isomerization in fluorescent protein chromophores involves addition/elimination.
AB  - The green fluorescent protein (GFP) chromophore undergoes both photochemical and
      thermal isomerizations. Typically, the Z form is more stable and undergoes
      photochemical conversion to the E form followed by thermal reversion over a
      period of seconds or minutes. Although the mechanism of the thermal reversion has
      been the subject of some investigations, the surprisingly low activation energy
      for this process has not sparked any controversy. We now show that the
      chromophore is surprisingly stable in both E and Z forms and that the facile
      thermal reversion is the result of a novel nucleophilic addition/elimination
      mechanism. This observation may have implications for the intervention of such
      processes, as well as blinking and kindling, in fluorescent proteins.

PMID- 18826309
TI  - N2 hydrogenation from activated end-on bis(indenyl) zirconium dinitrogen
      complexes.
AB  - Sodium amalgam reduction of the bis(indenyl)zirconium dihalide complexes, (eta5
      C9H5-1-iPr-3-Me)2ZrX2 (X = Cl, Br, I), yielded the corresponding end-on
      dinitrogen complexes, [(eta5-C9H5-1-iPr-3-Me)2Zr(NaX)]2(mu2, eta1, eta1-N2), with
      inclusion of 1 equiv of salt per zirconocene. The solid state structures of the
      chloro and iodo congeners establish short Zr N and elongated N N bonds,
      consistent with modest to strong activation of the coordinated dinitrogen
      molecule. Exposure of the N2 compounds to 1 atm of dihydrogen resulted in rapid N
      H bond formation to yield a hydrido zirconocene hydrazido compound concomitant
      with salt elimination. These studies establish a new structural type of
      zirconocene dinitrogen complex and demonstrate that side-on coordination of the
      N2 ligand in the ground state is not a prerequisite for dinitrogen hydrogenation.

PMID- 18826310
TI  - Mechanism of enzymatic Birch reduction: stereochemical course and exchange
      reactions of benzoyl-CoA reductase.
AB  - Dearomatizing benzoyl-coenzyme A reductases (BCR) from facultatively anaerobic
      bacteria are key enzymes in the anaerobic degradation of aromatic compounds. They
      catalyze the ATP-dependent reduction of benzoyl-CoA (BCoA) to cyclohexa-1,5-diene
      1-carboxyl-CoA (dienoyl-CoA). A Birch reduction mechanism involving alternate
      electron transfer and protonation steps has been proposed for BCR. In this work
      we reacted BCoA in H2O and D2O, and d5-BCoA in H2O with BCR and the second enzyme
      of the pathway, dienoyl-CoA hydratase (DCH). The 1,4 hydration product formed
      from the dienoyl-CoA, 6-hydroxycyclohex-1-ene-1-carbonyl-CoA, was analyzed by
      several NMR techniques. The results obtained indicate that BCR stereoselectively
      forms the trans-dienoyl-CoA product, and DCH stereoselectively catalyzes a trans
      1,4 water addition. Moreover, unexpected proton exchanges at C-2 and C-6 were
      observed. They indicate that a free radical intermediate with an unusual low pKa
      is formed during BCR catalysis. This finding provides evidence for the proposed
      Birch reduction mechanism of BCR and is in agreement with the established radical
      mechanism of homologous alpha-hydroxyacyl-CoA dehydratases.

PMID- 18826311
TI  - Reversible oxidative addition and reductive elimination of fluorinated disulfides
      at gold(I) thiolate complexes: a new ligand exchange mechanism.
AB  - Reaction of HAuCl4 x 3 H2O with excess HSAr (Ar = C6F5 or C6F4H) in ethanol,
      followed by addition of [Et4N]Cl, produced [Et4N][Au(SAr)4] (Ar = C6F5 (1a) or
      C6F4H (1b)) as red crystalline solids in high yield. These complexes are rare
      examples of homoleptic gold(III) thiolate complexes. The crystal structures 1
      show square planar geometry at the gold center with elongated Au-S bonds. Both
      complexes undergo reversible reductive elimination/oxidative addition processes
      in solution via thermal and photochemical pathways. Equilibrium constant and
      photostationary state measurements indicate that the relative importance of the
      two pathways depends on the nature of the aromatic groups. The metal-containing
      reductive elimination products, [Et4N][Au(SAr)2] (Ar = C6F5 (2a) or C6F4H (2b)),
      were confirmed by both independent synthesis and crystallographic
      characterization. Cross-reactions between either 1 or 2 and various disulfides
      led to ligand exchange via an addition-elimination process, a previously unknown
      reaction pathway for ligand exchange at gold(I) centers.

PMID- 18826312
TI  - Postsynthesis racemization and place exchange reactions. Another step to unravel
      the origin of chirality for chiral ligand-capped gold nanoparticles.
AB  - We examine how postsynthesis nanoparticle ligand shell modifications as a general
      approach can help in the understanding of currently proposed mechanisms for gold
      nanoparticle chirality. We compare the CD response of chirally decorated mixed
      monolayer-protected gold nanoparticles synthesized in situ with quasi-identical
      gold nanoparticles either prepared by place exchange reactions or subjected to an
      aqueous base, resulting in partial hydrolysis and simultaneous partial
      racemization. We find that the CD response at wavelengths where the free chiral
      ligand does not absorb strongly depends on the preparation conditions, i.e., in
      situ synthesis vs place exchange, and that postsynthesis racemization of the
      chiral ligand produces racemic nanoparticles with no CD response, i.e., no
      induction of a chiral bias during reductive nanoparticle formation. Considering
      all experimental results for the described gold nanoparticle system with a C12H24
      spacer between the nanoparticle surface and chiral center, the so-called "vicinal
      effect" with the formation of a supramolecular assembly of the chiral moieties
      seems to be active. Finally, we argue that postsynthesis nanoparticle ligand
      shell modifications such as racemization and/or place exchange reactions are very
      powerful tools to unravel contributions of the different gold nanoparticle
      chirality mechanisms.

PMID- 18826313
TI  - Fabrication of surface-supported low-dimensional polyimide networks.
AB  - Interest in thermal and chemical stability of surface-supported organic networks
      has stimulated recent attempts to covalently interlink adsorbed molecular species
      into extended nanostructures. We show, using low-temperature scanning tunneling
      microscopy, that imidization of anhydrides and amines adsorbed on Au(111) can be
      thermally initiated under controlled ultrahigh vacuum conditions. Using two types
      of amine-functionalized polyphenyl molecules together with the organic
      semiconductor PTCDA, monolayer thick linear polymeric strands and a porous
      polymeric network with nanoscale dimensions are obtained.

PMID- 18826314
TI  - An unexpected diethyl azodicarboxylate-promoted dehydrogenation of tertiaryamine
      and tandem reaction with sulfonyl azide.
AB  - It is shown here for the first time that diethyl azodicarboxylate promotes
      dehydrogenation of tertiaryamines to afford enamines, which subsequently take
      place in tandem reactions with sulfonyl azides to give the N-sulfonyl amidine
      derivatives. A number of different substituted tertiaryamines and sulfonyl azides
      can successfully be coupled, and several functionalized groups are tolerated in
      this system. The reaction described here is mild, general, and efficient, thus
      providing an extremely preferable method for synthesis of a variety of N-sulfonyl
      amidine derivatives.

PMID- 18826315
TI  - Stereochemical determination and complex biosynthetic assembly of etnangien, a
      highly potent RNA polymerase inhibitor from the myxobacterium Sorangium
      cellulosum.
AB  - A potent novel analogue of the natural macrolide antibiotic etnangien, a
      structurally unique RNA polymerase inhibitor from myxobacteria, is reported. It
      may be readily obtained from fermentation broths of Sorangium cellulosum and
      shows high antibiotic activity, comparable to that of etnangien. However, it is
      much more readily available than the notoriously labile authentic natural product
      itself. Importantly, it is stable under neutral conditions, allowing for
      elaborate NMR measurements for assignment of the 12 hydroxyl- and methyl-bearing
      stereogenic centers. The full absolute and relative stereochemistries of these
      complex polyketides were determined by a combination of extensive high-field NMR
      studies, including J-based configuration analysis, molecular modeling, and
      synthetic derivatization in combination with an innovative method based on
      biosynthetic studies of this polyketide which is also presented here. A first
      look into the solution conformation and 3D structure of these promising macrolide
      antibiotics is reported. Finally, the complete biosynthetic gene cluster was
      analyzed in detail, revealing a highly unusual and complex trans-AT type
      polyketide biosynthesis, which does not follow colinearity rules, most likely
      performs programmed iteration as well as module skipping, and exhibits HMG-CoA
      box-directed methylation.

PMID- 18826316
TI  - Design, synthesis, and evaluation of a lanthanide chelating protein probe: CLaNP
      5 yields predictable paramagnetic effects independent of environment.
AB  - Immobilized lanthanide ions offer the opportunity to refine structures of
      proteins and the complexes they form by using restraints obtained from
      paramagnetic NMR experiments. We report the design, synthesis, and spectroscopic
      evaluation of the lanthanide chelator, Caged Lanthanide NMR Probe 5 (CLaNP-5)
      readily attachable to a protein surface via two cysteine residues. The probe
      causes tunable pseudocontact shifts, alignment, paramagnetic relaxation
      enhancement, and luminescence, by chelating it to the appropriate lanthanide ion.
      The observation of single shifts and the finding that the magnetic susceptibility
      tensors obtained from shifts and alignment analyses are highly similar strongly
      indicate that the probe is rigid with respect to the protein backbone. By placing
      the probe at various positions on a model protein it is demonstrated that the
      size and orientation of the magnetic susceptibility tensor of the probe are
      independent of the local protein environment. Consequently, the effects of the
      probe are readily predictable using a protein structure only. These findings
      designate CLaNP-5 as a protein probe to deliver unambiguous high quality
      structural restraints in studies on protein-protein and protein-ligand
      interactions.

PMID- 18826317
TI  - Trigger mechanism for the catalytic hydrogen activation by monoiron (iron-sulfur
      cluster-free) hydrogenase.
AB  - A fully optimized model for the resting state of the active site of the third
      type of phylogenetically unrelated (monoiron) hydrogenase, iron-sulfur cluster
      free hydrogenase (Hmd), was constructed based on density functional calculations.
      This resting state structure shows good agreement with the experimental IR
      spectra. The calculations predict that the barrier for H2 cleavage in the
      presence of MPT+ is 18 kcal/mol lower than that in the absence of MPT+, a result
      that explains why the isotopic H2/D2O exchange catalyzed by Hmd is strictly
      dependent on the presence of MPT+. This difference is a result of the MPT+
      triggering the pyridone to provide electron density to allow the Fe to take a
      proton while transferring a hydride to the MPT+. These active site models and
      catalytic mechanism are useful in understanding this hydrogen activation for the
      design of novel hydrogenation catalysts and for low cost, high efficiency
      hydrogen generation.

PMID- 18826318
TI  - Polymorphism of a hexa-host: isolation of four different single-crystal phases by
      melt crystallization.
AB  - A hexa-host compound yields at least four polymorphic forms from its melt phase.
      All four phases have been characterized using single-crystal X-ray diffraction;
      two of the phases were obtained by means of thermal stress, and the different
      forms exhibit conformational polymorphism.

PMID- 18826319
TI  - Polyphenol-beta-casein complexes at the air/water interface and in solution:
      effects of polyphenol structure.
AB  - The interactions between proteins and plant polyphenols are responsible for
      astringency and haze formation in beverages and may participate in foam
      stabilization. The effect of phenolic compounds with different structures,
      namely, catechin (C), epicatechin (Ec), epigallocatechin (Egc), epicatechin
      gallate (EcG), and epigallocatechin gallate (EgcG), on the surface properties at
      the air/liquid interface of beta-casein, chosen as model protein, were monitored
      by tensiometry and ellipsometry. The formation of complexes in the bulk phase was
      measured by electrospray ionization mass spectrometry (ESI-MS). Adsorption of
      polyphenols from pure solution was not observed. Surface pressure, surface
      concentration, and dilational modulus of the protein adsorption layer were
      greatly modified in the presence of galloylated flavanol monomers (EcG and EgcG)
      but not of lower molecular weight polyphenols (<306 g/mol). The formation of
      polyphenol-protein aggregates in the bulk, as evidenced by ESI-MS and light
      scattering experiments, was related to the slowdown of protein adsorption.

PMID- 18826320
TI  - Benzylglucosinolate, benzylisothiocyanate, and myrosinase activity in papaya
      fruit during development and ripening.
AB  - Papaya is a climacteric fruit that has high amounts of benzylglucosinolates (BG)
      and benzylisothiocyanates (BITC), but information regarding levels of BG or BITC
      during fruit development and ripening is limited. Because BG and BITC are
      compounds of importance from both a nutritional and a crop yield standpoint, the
      aim of this work was to access data on the distribution and changes of BG and
      BITC levels during fruit development and ripening. BG and BITC levels were
      quantified in peel, pulp, and seeds of papaya fruit. Volatile BITC was also
      verified in the internal cavity of the fruit during ripening. The influence of
      the ethylene in BG and BITC levels and mirosinase activity was tested by exposing
      mature green fruits to ethylene and 1-methylcyclopropene (1-MCP). The highest BG
      levels were detected in seeds, followed by the peel and pulp being decreased in
      all tissues during fruit development. Similarly, the levels of BITC were much
      higher in the seeds than the peel and pulp. The levels of BG for control and
      ethylene-treated fruit were very similar, increasing in the pulp and peel during
      late ripening but not changing significantly in seeds. On the other hand, fruit
      exposed to 1-MCP showed a decrease in BG amount in the pulp and accumulation in
      seed. The treatments did not result in clear differences regarding the amount of
      BITC in the pulp and peel of the fruit. According to the results, ethylene does
      not have a clear effect on BITC accumulation in ripening papaya fruit. The fact
      that BG levels in the pulp did not decrease during ripening, regardless of the
      treatment employed, and that papaya is consumed mainly as fresh fruit, speaks in
      favor of this fruit as a good dietary source for glucosinolate and
      isothiocyanates.

PMID- 18826321
TI  - Tandem palladium-catalyzed N,C-coupling/carbonylation sequence for the synthesis
      of 2-carboxyindoles.
AB  - Tandem palladium-catalyzed N,C-coupling/carbonylation, under 10 atm of carbon
      monoxide and at 110 degrees C, is a novel and efficient method for the
      preparation of 2-carboxyindoles. The catalyst system tolerates a variety of
      functional groups, and the noted indoles were obtained in good isolated yields.

PMID- 18826322
TI  - Motif-programmed artificial extracellular matrix.
AB  - Motif-programming is a method for creating artificial proteins by combining
      functional peptide motifs in a combinatorial manner. This method is particularly
      well suited for developing liaison molecules that interface between cells and
      inorganic materials. Here we describe our creation of artificial proteins through
      the programming of two motifs, a natural cell attachment motif (RGD) and an
      artificial Ti-binding motif (minTBP-1). The created proteins were found to
      reversibly bind Ti and to bind MC3T3-E1 osteoblast-like cells. Moreover, although
      the interaction with Ti was not covalent, the proteins recapitulated several
      functions of fibronectin, and thus, could serve as an artificial ECM on Ti
      materials. Because this motif-programming system could be easily extended to
      create artificial proteins having other biological functions and material
      specificities, it should be highly useful for application to tissue engineering
      and regenerative medicine.

PMID- 18826323
TI  - Manipulating the salt and thermal stability of DNA multilayer films via
      oligonucleotide length.
AB  - DNA films are promising materials for diverse applications, including sensing,
      diagnostics, and drug/gene delivery. However, the ability to tune the stability
      of DNA films remains a crucial aspect for such applications. Herein, we examine
      the role of oligonucleotide length on the formation, and salt and thermal
      stability, of DNA multilayer films using oligonucleotides of homopolymeric
      diblocks (polyAG and polyTC), with each block (A, G, T, or C) ranging from 5 to
      30 bases (10-, 20-, 30-, 40-, and 60-mer). Using a combination of quartz crystal
      microgravimetry, dual polarization interferometry, and flow cytometry, we
      demonstrate that at least 10 bases per hybridizing block in the DNA diblocks
      (that is, 20-mer) are required for successful hybridization and, hence, DNA
      multilayer film formation. Films assembled using longer oligonucleotide blocks
      were more stable in low salt conditions, with the DNA multilayer films assembled
      from the 60-mer oligonucleotides remaining intact in solutions of about 25 mM
      NaCl. A systematic increase in film melting temperature ( T m) was observed for
      the DNA multilayer films (assembled on colloids) with increasing oligonucleotide
      length, ranging from 38.5 degrees C for the 20-mer films to 53 degrees C for the
      60-mer films. Further, an alternating trend in T m of the DNA multilayer films
      was observed with layer number (AG or TC); DNA multilayer films terminated with
      an AG layer exhibited a higher T m (44-49 degrees C) than films with an outermost
      TC layer (ca. 38 degrees C), suggesting a rearrangement of the film structure
      upon hybridization of the outermost layer. This work shows that the stability of
      DNA multilayer films can be tuned by varying the length of the oligonucleotide
      building blocks, thus providing a versatile means to tailor the salt and thermal
      stability of DNA films, which is necessary for the application of such films.

PMID- 18826324
TI  - Elimination of beta-thioalkoxy alcohols under Mitsunobu conditions. A new
      synthesis of conjugated enynes from propargylic dithioacetals.
AB  - Treatment of propargylic dithiolanes 1 with (n)BuLi followed by a carbonyl
      electrophile yields the corresponding homopropargylic alcohol 3. Upon treatment
      with 2 equiv of PPh3 and DIAD, elimination of SR and OH moieties from 3 affords
      the corresponding olefins 4 in moderate to good yield. The reaction can be
      considered an alternative of McMurry coupling of two different carbonyl
      equivalents.

PMID- 18826325
TI  - The Curtius rearrangement of cyclopropyl and cyclopropenoyl azides. A combined
      theoretical and experimental mechanistic study.
AB  - A combined experimental and theoretical study addresses the concertedness of the
      thermal Curtius rearrangement. The kinetics of the Curtius rearrangements of
      methyl 1-azidocarbonyl cycloprop-2-ene-1-carboxylate and methyl 1-azidocarbonyl
      cyclopropane-1-carboxylate were studied by (1)H NMR spectroscopy, and there is
      close agreement between calculated and experimental enthalpies and entropies of
      activation. Density functional theory (DFT) calculations (B3LYP/6-311+G(d,p)) on
      these same acyl azides suggest gas phase barriers of 27.8 and 25.1 kcal/mol. By
      comparison, gas phase activation barriers for the rearrangement of acetyl,
      pivaloyl, and phenyl azides are 27.6, 27.4, and 30.0 kcal/mol, respectively. The
      barrier for the concerted Curtius reaction of acetyl azide at the CCSD(T)/6
      311+G(d,p) level exhibited a comparable activation energy of 26.3 kcal/mol.
      Intrinsic reaction coordinate (IRC) analyses suggest that all of the
      rearrangements occur by a concerted pathway with the concomitant loss of N2. The
      lower activation energy for the rearrangement of methyl 1-azidocarbonyl cycloprop
      2-ene-1-carboxylate relative to methyl 1-azidocarbonyl cyclopropane-1-carboxylate
      was attributed to a weaker bond between the carbonyl carbon and the three
      membered ring in the former compound. Calculations on the rearrangement of
      cycloprop-2-ene-1-oyl azides do not support pi-stabilization of the transition
      state by the cyclopropene double bond. A comparison of reaction pathways at the
      CBS-QB3 level for the Curtius rearrangement versus the loss of N2 to form a
      nitrene intermediate provides strong evidence that the concerted Curtius
      rearrangement is the dominant process.

PMID- 18826326
TI  - Synthesis of the phosphinic analogue of thyrotropin releasing hormone.
AB  - The synthesis of the phosphinic analogue of thyrotropin releasing hormone (TRH)
      GlpPsi[P(O)(OH)]HisProNH2, where the scissile peptide bond of TRH has been
      replaced by the hydrolytically stable phosphinic bond, has been achieved by a
      multistep synthetic strategy, providing thus one of the most potent synthetic
      inhibitors of pyroglutamyl peptidase II (PPII) reported to date (170 nM). The key
      synthetic step, an Ugi-type condensation reaction, produced directly the suitably
      protected for solid-phase peptide synthesis pseudodipeptidic block
      FmocGlu(OMe)Psi[P(O)(OH)]His(Tr)OH. Formation of the pyroglutamic ring was
      performed on solid phase, providing thus a general method for synthesizing
      pyroglutamyl phosphinic peptides on solid phase. Using this strategy, the
      phosphinic analogue of TRH has been synthesized for the first time.

PMID- 18826327
TI  - A convenient method for the preparation of fluorous tin derivatives for the
      fluorous labeling strategy.
AB  - A convenient method for the preparation of fluorous aryl stannanes was developed
      as a means of expanding the general utility of the fluorous labeling strategy
      (FLS). Following the synthesis of a novel fluorous distannane, a palladium
      catalyzed cross-coupling reaction was used to prepare the target compounds from
      aryl halides. The scope of the reaction was investigated by preparing a small
      library of model compounds where the reaction yields were similar to those
      reported for the analogous procedures employing hexamethyl- or
      hexabutyldistannanes. The utility of the reported methodology was demonstrated
      through the successful synthesis of fluorous precursors to two established
      molecular imaging and therapy agents (FIAU, IUdR). These were radiolabeled with
      iodine-125 and the desired products isolated in high yield and effective specific
      activity.

PMID- 18826328
TI  - Analysis of IgA1 N-glycosylation and its contribution to FcalphaRI binding.
AB  - The IgA isotype of human antibodies triggers inflammatory responses via the IgA
      specific receptor FcalphaRI (CD89). Structural studies have suggested that IgA1 N
      glycans could modulate the interaction with FcalphaRI. We have carried out
      detailed biophysical analyses of three IgA1 samples purified from human serum and
      recombinant IgA1-Fc and compared their binding to FcalphaRI. Analytical
      ultracentrifugation revealed wide variation in the distribution of polymeric
      species between IgA1 samples, and Fourier transform ion cyclotron resonance mass
      spectrometry showed overlapping but distinct populations of N-glycan species
      between IgA1 samples. Kinetic and equilibrium data from surface plasmon resonance
      experiments revealed that variation in the IgA1 C H2 N-glycans had no effect on
      the kinetics or affinity constants for binding to FcalphaRI. Indeed, complete
      enzymatic removal of the IgA1 N-glycans yielded superimposable binding curves.
      These findings have implications for renal diseases such as IgA nephropathy.

PMID- 18826330
TI  - Advocates of animal experimentation: what's in a name?

PMID- 18826329
TI  - Identification of the substrate radical intermediate derived from ethanolamine
      during catalysis by ethanolamine ammonia-lyase.
AB  - Rapid-mix freeze-quench (RMFQ) methods and electron paramagnetic resonance (EPR)
      spectroscopy have been used to characterize the steady-state radical in the
      deamination of ethanolamine catalyzed by adenosylcobalamin (AdoCbl)-dependent
      ethanolamine ammonia-lyase (EAL). EPR spectra of the radical intermediates formed
      with the substrates, [1-13C]ethanolamine, [2-13C]ethanolamine, and unlabeled
      ethanolamine were acquired using RMFQ trapping methods from 10 ms to completion
      of the reaction. Resolved 13C hyperfine splitting in EPR spectra of samples
      prepared with [1-13C]ethanolamine and the absence of such splitting in spectra of
      samples prepared with [2-13C]ethanolamine show that the unpaired electron is
      localized on C1 (the carbinol carbon) of the substrate. The 13C splitting from C1
      persists from 10 ms throughout the time course of substrate turnover, and there
      was no evidence of a detectable amount of a product like radical having unpaired
      spin on C2. These results correct an earlier assignment for this radical
      intermediate [Warncke, K., et al. (1999) J. Am. Chem. Soc. 121, 10522-10528]. The
      EPR signals of the substrate radical intermediate are altered by electron spin
      coupling to the other paramagnetic species, cob(II)alamin, in the active site.
      The dipole-dipole and exchange interactions as well as the 1-13C hyperfine
      splitting tensor were analyzed via spectral simulations. The sign of the
      isotropic exchange interaction indicates a weak ferromagnetic coupling of the two
      unpaired electrons. A Co2+-radical distance of 8.7 A was obtained from the
      magnitude of the dipole-dipole interaction. The orientation of the principal axes
      of the 13C hyperfine splitting tensor shows that the long axis of the spin
      bearing p orbital on C1 of the substrate radical makes an angle of approximately
      98 degrees with the unique axis of the d(z2) orbital of Co2+.

PMID- 18826331
TI  - An assessment of the role of chimpanzees in AIDS vaccine research.
AB  - Prior to Simian Immunodeficiency Virus (SIV)-infected macaques becoming the
      'model of choice' in the 1990s, chimpanzees were widely used in AIDS vaccine
      research and testing. Faced with the continued failure to develop an effective
      human vaccine, some scientists are calling for a return to their widespread use.
      To assess the past and potential future contribution of chimpanzees to AIDS
      vaccine development, databases and published literature were systematically
      searched to compare the results of AIDS vaccine trials in chimpanzees with those
      of human clinical trials, and to determine whether the chimpanzee trials were
      predictive of the human response. Protective and/or therapeutic responses have
      been elicited in chimpanzees, via: passive antibody transfer; CD4 analogues;
      attenuated virus; many types and combinations of recombinant HIV proteins; DNA
      vaccines; recombinant adenovirus and canarypox vaccines; and many multi-component
      vaccines using more than one of these approaches. Immunogenicity has also been
      shown in chimpanzees for vaccinia-based and peptide vaccines. Protection and/or
      significant therapeutic effects have not been demonstrated by any vaccine to date
      in humans. Vaccine responses in chimpanzees and humans are highly discordant.
      Claims of the importance of chimpanzees in AIDS vaccine development are without
      foundation, and a return to the use of chimpanzees in AIDS research/vaccine
      development is scientifically unjustifiable.

PMID- 18826332
TI  - Beta-defensin antibiotic peptides in the innate immunity of the buffalo: in vivo
      and in vitro studies.
AB  - Beta-defensin antimicrobial peptides are multifunctional biomolecules, which are
      a major component of the oxygen-independent microbicidal system of buffalo
      polymorphonuclear (PMN) cells. They have great potential for use as proteomic
      biomarkers of host cell responses in the presence of microbial agents. On
      purifying these peptides by RP-HPLC, four defensin peptides were revealed. The
      results from testing against Escherichia coli, Staphylococcus aureus,
      Streptococcus pyogenes, Candida albicans, Rinderpest Virus (RPV) and Newcastle
      Disease Virus (NDV), showed that the peptides possessed antimicrobial and
      antiviral activities. Minimum inhibitory concentration (MIC) values varied
      according to the peptide amounts and the exposure time. Furthermore, an increase
      in the levels of these cationic antimicrobial peptides was apparent in milk
      obtained from natural cases of mastitis, as compared to the levels in normal
      milk. MALDI-TOF-based amino acid sequencing confirmed the expression of two beta
      defensins (LAP and BNBD-2) in mastitis milk. A comparison of peptide sequences
      revealed that buffalo LAP and BNBD-2 share 98.6% and 100% sequence identity,
      respectively, with those of cattle. In vitro, Bovine Viral Diarrhoea Virus (BVDV)
      infection was shown to induce the expression of the beta-defensin gene, as
      evidenced by the PCR amplification of cDNA with specific primers. The
      determination of the enhanced expression of beta-defensin peptides in mastitis
      milk and in PMN cells, can be considered as an advanced approach to the
      assessment of cellular and molecular responses to cell injury. It is hoped that
      in vitro studies on phagocytes such as PMN cells and other cell lines, will
      eventually replace the use of animals in elucidating the roles of these cytokines
      in response to microbe-derived cell damage. It will also be possible to use
      defensins as biomarkers to correlate failure in host cell defence systems with
      peptide heterogeneity.

PMID- 18826333
TI  - Reconstructed epidermis and full-thickness skin for absorption testing: influence
      of the vehicles used on steroid permeation.
AB  - A protocol for percutaneous absorption studies has been validated, based on the
      use of reconstructed human epidermis (RHE) and aqueous solutions of test
      substances. However, it is often the case that it is more-complex formulations of
      drugs or chemicals which will make contact with the skin surface. To investigate
      whether RHE and the reconstructed full-thickness skin model (FT-model) can be
      used to predict uptake from formulations, we compared the permeation of
      hydrocortisone and testosterone when applied in emulsion form and as a solution
      containing the penetration enhancer, ethanol. Human and pig skin and a non
      cornified alveolar model served as references. The results were compared with
      steroid release from the formulations. The permeation rates of the steroids were
      ranked as: alveolar model >> RHE > FT-model, pig skin > human skin. In accordance
      with the rapid hydrocortisone release from the formulations, the permeation rates
      of this steroid exceeded those of testosterone. Only minor differences were
      observed when comparing the testosterone formulations, in terms of release and
      permeation. However, the ranking of the permeation of the hydrocortisone
      formulations was: solution > w/o emulsion > o/w emulsion, which permitted the
      elucidation of penetration enhancing effects, which is not possible with drug
      release studies. Differences in penetration were most obvious with native skin
      and reconstructed tissues, which exhibited a well-developed penetration barrier.
      In conclusion, RHE and skin preparations may be useful in the development of
      topical dermatics, and in the framework of hazard analysis of toxic compounds and
      their various formulations.

PMID- 18826334
TI  - Dissemination strategies: how do they influence the uptake of the new Three Rs
      methods across laboratories and other boundaries? A report of a workshop held by
      the European Partnership for Alternative Approaches to Animal Testing (EPAA)
      Working Group 3.

PMID- 18826335
TI  - Barriers to validation: a report by the European Partnership fo Alternative
      Approaches to Animal Testing (EPAA) Working Group 5.

PMID- 18826336
TI  - Home Office licence abstracts--an assessment.
AB  - Since late in 2004, brief abstracts of projects licensed under the Animals
      (Scientific Procedures) Act 1986 have been published on the Home Office website.
      These are produced by the Project Licence Holders, and their publication is seen
      by the Home Office as contributing to greater openness and to greater public
      understanding of the use of animals in science, and how it is regulated. Here, we
      assess the value of the database for this purpose, based on an examination of the
      1400 abstracts published up to January 2008. The abstracts are generally strong
      on justification, but often very poor at describing the likely effects on the
      animals used. In many cases, they lack basic information on the procedures
      applied, and the numbers, and even the species, of animals involved. A
      significant number of projects lack abstracts altogether. In order to ensure that
      the database gives a complete and balanced picture of animal use in research, we
      consider that it should be mandatory to submit an abstract, which should include
      at least the species and numbers of animals used, the adverse effects they are
      likely to experience, and the severity limits assigned to the procedures applied
      to them. The value of the database would also be improved greatly, if it were
      more readily searchable, at least by species, level of severity, and broad area
      of research.

PMID- 18826337
TI  - Assays on the influence of biomaterials on allogeneic rejection in tissue
      engineering.
AB  - In tissue engineering, innate responses to biomaterial scaffolds will affect
      rejection of allogeneic cells. Biomaterials directly influence innate and
      adaptive immune cell adhesion, reactive oxygen intermediate production, cytokine
      secretion, nuclear factor-kappa B nuclear translocation, gene expression, and
      cell surface markers, all of which are likely to affect allogeneic rejection
      responses. A major goal in tissue engineering is to induce transplant tolerance,
      potentially by manipulating the biomaterial component. This review describes
      methods of measuring responses of macrophages, dendritic cells, and T cells
      stimulated in vitro and in vivo and addresses key factors in assay development.
      Such tests include mixed leukocyte reactions, enzyme-linked immunosorbent spot
      assays, trans-vivo delayed-type hypersensitivity assays, and measurement of
      dendritic cell subsets and anti-donor antibodies; we propose extending these
      studies to tissue engineering.

PMID- 18826338
TI  - Proteins and their peptide motifs in acellular apatite mineralization of
      scaffolds for tissue engineering.
AB  - Many proteins in the inorganic/organic matrix of bone induce or modulate or
      inhibit mineralization of apatite in vivo. Many attempts have been made to mimic
      and understand this mechanism as part of bone formation, and ectopic
      mineralization and control thereof. Many attempts have also been made to use such
      proteins or protein fragments to harness their potential for improved
      mineralization. Such proteins and peptide motifs have also been the inspiration
      for attempts of making mimics of their structures and motifs using chemical or
      biological synthesis. The aim of this review is to highlight how proteins and
      (poly)peptides themselves impact mineralization in the human body, and how those
      could be used and have been used for improving apatite mineralization, for
      example, on or in materials that by themselves do not induce apatite
      mineralization but otherwise have interesting properties for use as bone tissue
      engineering scaffolds.

PMID- 18826339
TI  - Enhanced chondrogenesis of mesenchymal stem cells in collagen mimetic peptide
      mediated microenvironment.
AB  - A new type of synthetic hydrogel scaffold that mimics certain aspects of
      structure and function of natural extracellular matrix (ECM) has been developed.
      We previously reported the conjugation of collagen mimetic peptide (CMP) to
      poly(ethylene oxide) diacrylate (PEODA) to create a polymer-peptide hybrid
      scaffold for a suitable cell microenvironment. In this study, we showed that the
      CMP-mediated microenvironment enhances the chondrogenic differentiation of
      mesenchymal stem cells (MSCs). MSCs were harvested and photo-encapsulated in CMP
      conjugated PEODA (CMP/PEODA). After 3 weeks, the histological and biochemical
      analysis of the CMP/PEODA gel revealed twice as much glycosaminoglycan and
      collagen contents as in control PEODA hydrogels. Moreover, MSCs cultured in
      CMP/PEODA hydrogel exhibited a lower level of hypertrophic markers, core binding
      factor alpha 1, and type X collagen than MSCs in PEODA hydrogel as revealed by
      gene expression and immunohistochemisty. These results indicate that CMP/PEODA
      hydrogel provides a favorable microenvironment for encapsulated MSCs and
      regulates their downstream chondrogenic differentiation.

PMID- 18826340
TI  - Enhanced in vitro chondrogenesis of primary mesenchymal stem cells by combined
      gene transfer.
AB  - Because articular cartilage has a poor regeneration capacity, numerous cell-based
      approaches to therapy are currently being explored. The present study involved
      the use of gene transfer as a means to provide sustained delivery of chondrogenic
      proteins to primary mesenchymal stem cells (MSCs). In previous work, we found
      that adenoviral-mediated gene transfer of transforming growth factor-beta1 (TGF
      beta1) and bone morphogenetic protein 2 (BMP-2), but not insulin-like growth
      factor 1 (IGF-1), could be used to induce chondrogenic differentiation of MSCs in
      an aggregate culture system. In the present study, we examined the effects on
      chondrogenesis of these transgenes when delivered in combination. Cultures of
      bone marrow-derived MSCs were infected with 2.5 x 10(2) or 2.5 x 10(3) viral
      particles/cell of each adenoviral vector individually, or in combination, seeded
      into aggregates, and cultured for 3 weeks in a defined serum-free medium. Levels
      of transgene product in the medium were initially high, approximately 100 ng/mL
      TGF-beta1, 120 ng/mL BMP-2, and 80 ng/mL IGF-1 at day 3, and declined thereafter.
      We found that co-expression of IGF-1 and TGF-beta1, BMP-2, or both at low doses
      resulted in larger aggregates, higher levels of glycosaminoglycan synthesis,
      stronger staining for proteoglycans and collagen type II and X, and greater
      expression of cartilage-specific marker genes than with either transgene alone.
      Gene-induced chondrogenesis of MSCs using multiple genes that act synergistically
      may enable the administration of reduced viral doses in vivo and could be of
      considerable benefit for the development of cell-based therapies for cartilage
      repair.

PMID- 18826342
TI  - New beginnings.

PMID- 18826341
TI  - Toward development and production of human T cells in swine for potential use in
      adoptive T cell immunotherapy.
AB  - Immunotherapy and vaccination for cancer or infection are generally approached by
      administration of antigen or stimulation of antigen-presenting cells or both.
      These measures may fail if the treated individual lacks T cells specific for the
      immunogen(s). We tested another strategy-the generation of new T cells from
      hematopoietic stem cells that might be used for adoptive immunotherapy. To test
      this concept, we introduced T cell-depleted human bone marrow cells into fetal
      swine and tested the swine for human T cells at various times after birth. Human
      T cells were detected in the thymus and blood of the treated swine. These cells
      were generated de novo as they contained human T cell receptor excision circles
      not present in the T cell-depleted bone marrow. The human T cells were highly
      diverse and included novel specificities capable of responding to antigen
      presented by human antigen-presenting cells. Our findings constitute a first step
      in a new promising approach to immunotherapy in which tumor- or virus-specific T
      cell clones lacking in an individual might be generated in a surrogate host from
      hematopoietic stem cells of the individual to be treated.

PMID- 18826343
TI  - Navigating the Strait of Magellan: mapping a new paradigm for neurosurgical
      residency training. Presidential address to the Society of Neurological Surgeons,
      May 7, 2007.
AB  - At the conclusion of his year as 81st president of the Society of Neurological
      Surgeons, the author delivered the following address at the 2007 annual meeting
      of the Society of Neurological Surgeons in San Francisco. In his address, Dr.
      Popp used the voyage of Ferdinand Magellan to illustrate the present climate
      affecting residency training and why the current training paradigm must be
      examined and, where necessary, changed. Based on this call to action the leaders
      of the American Association of Neurological Surgeons, The American Board of
      Neurological Surgeons, The Congress of Neurological Surgeons, The Council of
      State Neurosurgical Societies, The Residency Review Committee for Neurosurgery,
      The Society of Neurological Surgeons, and the Washington Committee for
      Neurosurgery agreed to hold an unprecedented Education Summit meeting to
      investigate a comprehensive approach to evaluating and changing the current
      neurosurgical residency training model.

PMID- 18826344
TI  - Intraoperative mapping of language functions: a longitudinal neurolinguistic
      analysis.
AB  - OBJECT: This prospective longitudinally designed study was conducted to evaluate
      language functions pre- and postoperatively in patients who underwent
      microsurgical treatment of tumors in close proximity to or within language areas
      and to detect those patients at risk for a postoperative aphasic disturbance.
      METHODS: Between 1991 and 2005, 153 awake craniotomies with subsequent cortical
      mapping of language functions were performed in 149 patients. Language functions
      were assessed using a standardized test battery. Risk factors were obtained from
      multivariate logistic regression models. RESULTS: Language mapping was able to be
      performed in all patients, and complete tumor resection was achieved in 48.4%.
      Within 21 days after surgery a new language deficit (aphasic disturbance) was
      observed in 41 (32%) of the 128 cases without preoperative deficits. There were a
      total of 60 cases involving postoperative aphasic disturbances, including cases
      both with and without preoperative disturbances. Risk factors for postoperative
      aphasic disturbance were preoperative aphasia (p<0.0002), intraoperative
      complications (p<0.02), language-positive sites within the tumor (p<0.001), and
      nonfrontal lesion location (p<0.001). In patients without a preoperative deficit,
      a normal (yet submaximal) naming performance was a powerful predictor for an
      early postoperative aphasic disturbance (p<0.0003). Seven months after treatment
      10.9% of the 128 cases without preoperative aphasic disturbances continued to
      demonstrate new postoperative language disturbances. A total of 17.6% of all
      cases demonstrated new postoperative language disturbances after 7 months. Risk
      factors for persistent aphasic disturbance were increased age (>40 years, p<0.02)
      and preoperative aphasia (p<0.001). CONCLUSIONS: Every attempt should be
      undertaken to preserve language-relevant areas intraoperatively, even when they
      are located within the tumor. New postoperative deficits resolve in the majority
      of patients, which may be a result of cortical mapping as well as functional
      reorganization.

PMID- 18826345
TI  - Somatosensory, motor, and reaching/grasping responses to direct electrical
      stimulation of the human cingulate motor areas.
AB  - OBJECT: Surgery for frontal lobe drug-resistant epilepsies is often limited by
      the apparent widespread distribution of the epileptogenic zone. Recent advances
      in the parcellation of the medial premotor cortex give the opportunity to
      reconsider "seizures of the supplementary motor area" (SMA), and to assess the
      contribution of cingulate motor areas (CMAs), SMA proper (SMAp), and pre-SMA to
      the symptomatology of premotor seizures. METHODS: The authors reviewed the
      results of extraoperative electrical stimulation (ES) applied in 52 candidates
      for epilepsy surgery who underwent stereotactic intracerebral
      electroencephalographic recordings, focusing on ES of the different medial
      premotor fields; that is, the anterior and posterior CMA, the SMAp, and the pre
      SMA. The ES sites were localized by superposition of the postoperative lateral
      skull x-ray and the preoperative sagittal MR imaging studies. RESULTS: Among 94
      electrodes reaching the medial premotor wall, 57 responses were obtained from the
      anterior CMA (13 cases), the posterior CMA (11), the pre-SMA (18), and the SMAp
      (15). The ES of the pre-SMA and SMAp gave rise most often to a combination of
      motor (31 cases), speech-related (22), or somatosensory (3) elementary symptoms.
      The ES of the CMA yielded simple (17 of 24) more often than complex responses (7
      of 24), among which sensory symptoms (7) were overrepresented. Irrepressible
      exploratory reaching/grasping movements were elicited at the vicinity of the
      cingulate sulcus, from the anterior CMA (3 cases) or the pre-SMA (1). Clinical
      responses to ES were not predictive of the postoperative neurological outcome.
      CONCLUSIONS: These findings might be helpful in epilepsy surgery candidates, to
      better target investigation of the CMA, pre-SMA, and SMAp, and therefore to
      provide a better understanding of premotor seizures.

PMID- 18826346
TI  - Extraoperative functional mapping of motor areas in epileptic patients by high
      frequency cortical stimulation.
AB  - OBJECT: The aim of this study was to investigate the usefulness of a short train
      of high-frequency (500 Hz) cortical stimulation to delineate the primary motor
      cortex (MI), supplementary motor area (SMA), primary somatosensory cortex (SI),
      supplementary sensory area (SSA), negative motor area (NMA), and supplementary
      negative motor area (SNMA) in patients with epilepsy who were undergoing
      functional mapping. METHODS: Seventeen patients were studied, all of whom
      underwent functional mapping using 50-Hz electrical stimulation. After these
      clinical evaluations, cortical stimulations with a short train of electrical
      pulses at 500 Hz were performed through subdural electrodes placed at the MI,
      SMA, SI, SSA, NMA, and SNMA, which had been identified by 50-Hz stimulation, and
      surrounding cortical areas, while surface electromyography readings were
      recorded. RESULTS: Stimulation of the MI elicited motor evoked potentials (MEPs)
      in contralateral muscles. Stimulation of the SMA also induced MEPs in
      contralateral muscles but with longer latencies compared with the MI stimulation.
      Stimulation of the SMA did not elicit MEPs in ipsilateral muscles. Stimulation of
      the SI, SSA, NMA, and SNMA did not induce MEPs in any muscle. In one patient,
      MEPs were elicited without seizure induction by 500-Hz stimulation of the
      electrodes, whereas a 50-Hz stimulation of the same electrodes induced his
      habitual seizures. CONCLUSIONS: Extraoperative high-frequency stimulation with
      MEP monitoring is a useful complementary method for cortical mapping without
      inducing seizure. Stimulation of SMA induces MEPs in contralateral muscles, with
      longer latencies compared with the stimulation of MI. This finding may be useful
      for the differentiation between MI and SMA, especially in the foot motor areas.

PMID- 18826347
TI  - Long-term brain plasticity allowing a multistage surgical approach to World
      Health Organization Grade II gliomas in eloquent areas.
AB  - Although the goal of surgery for World Health Organization Grade II gliomas is
      maximal extent of resection, complete tumor removal is not always possible when
      the glioma involves eloquent areas. The authors propose a multistage surgical
      approach to highly crucial areas that are classically considered inoperable,
      enabling optimization of the extent of resection while avoiding permanent
      cognitive deficits due to induced functional reshaping in the interim between the
      2 consecutive operations. To demonstrate such plasticity, the authors used a
      combination of sequential functional MR imaging and intraoperative electrical
      stimulation mapping before and during surgeries spaced by several years in 2
      patients who each underwent 2 separate resections of Grade II gliomas located in
      the left dominant premotor area. During several years of follow-up after the
      first procedure, both patients had unremarkable examination results and normal
      socioprofessional lives. There was no malignant transformation. Based on their
      experience with these cases, the authors suggest that in cases of incomplete
      glioma removal, a second operation before anaplasia should be considered, made
      possible by brain reorganization after the first operation.

PMID- 18826348
TI  - Deep brain stimulation in the treatment of obesity.
AB  - Obesity is a growing global health problem frequently intractable to current
      treatment options. Recent evidence suggests that deep brain stimulation (DBS) may
      be effective and safe in the management of various, refractory neuropsychiatric
      disorders, including obesity. The authors review the literature implicating
      various neural regions in the pathophysiology of obesity, as well as the evidence
      supporting these regions as targets for DBS, in order to explore the therapeutic
      promise of DBS in obesity. The lateral hypothalamus and ventromedial hypothalamus
      are the appetite and satiety centers in the brain, respectively. Substantial data
      support targeting these regions with DBS for the purpose of appetite suppression
      and weight loss. However, reward sensation associated with highly caloric food
      has been implicated in overconsumption as well as obesity, and may in part
      explain the failure rates of conservative management and bariatric surgery. Thus,
      regions of the brain's reward circuitry, such as the nucleus accumbens, are
      promising alternatives for DBS in obesity control. The authors conclude that deep
      brain stimulation should be strongly considered as a promising therapeutic option
      for patients suffering from refractory obesity.

PMID- 18826349
TI  - Deep brain stimulation as an effective treatment option for post-midbrain
      infarction-related tremor as it presents with Benedikt syndrome.
AB  - Benedikt syndrome is a rare but debilitating constellation of symptoms that
      manifests from infarction of the red nucleus, cerebral peduncle, oculomotor
      fascicles, and lower oculomotor nucleus. Clinically, it presents as ipsilateral
      cranial nerve III palsy, contralateral hemiataxia with intention tremor,
      contralateral hemiparesis, and hyperactive tendon reflexes. Commonly, the tremor
      upon purposeful movement proves to be the most debilitating manifestation of the
      infarction with significant impact on the patient's ability to perform activities
      of daily living and, therefore, quality of life. The authors report the
      successful management of this debilitating post-midbrain infarction tremor with
      the insertion of a deep brain stimulator with targets in the contralateral
      lenticular fasciculus.

PMID- 18826350
TI  - Factors involved in long-term efficacy of deep brain stimulation of the thalamus
      for essential tremor.
AB  - OBJECT: Although nucleus ventralis intermedius stimulation has been shown to be
      safe and efficacious in the treatment of essential tremor, there is a subset of
      patients who eventually lose benefit from their stimulation. Proposed causes for
      this phenomenon include tolerance, disease progression, and suboptimal location.
      The goal of this study was to assess the factors that may lead to both
      stimulation failure, defined as loss of meaningful tremor relief, and less
      satisfactory outcomes, defined as leads requiring voltages>3.6 V for effective
      tremor control. METHODS: The authors present their clinical outcomes from 31
      leads in 27 patients who had effective tremor control for >1 year following
      nucleus ventralis intermedius stimulation. All patients postoperatively had a
      mean decrease in both the writing and drawing subscales of the Fahn-Tolosa-Marin
      Tremor Rating Scale (p<0.001). RESULTS: After a mean follow-up of 40 months, 22
      patients continued to have tremor control with stimulation. Four patients
      eventually lost efficacy of their stimulation at a mean of 39 months. There was
      no difference in age, duration of disease, or disease severity between the
      groups. Examination of perioperative factors revealed that suboptimal
      anteroposterior positioning as evidenced on intraoperative fluoroscopy occurred
      significantly more frequently in patients with stimulation failure (p=0.018). In
      patients with less satisfactory outcomes, no difference was seen between group
      demographics. Fluoroscopy again revealed suboptimal positioning more frequently
      in these patients (p=0.005). CONCLUSIONS: This study provides further evidence
      that suboptimal lead position in combination with disease progression or
      tolerance may result in less satisfactory long-term outcomes.

PMID- 18826351
TI  - Direct epidural electrical stimulation of the optic nerve: a new method for
      intraoperative assessment of function.
AB  - Intraoperative visual system monitoring of lesions with a close relationship to
      the optic apparatus by using light flashes reportedly is difficult to perform,
      and the results are too unreliable to interpret. The authors used direct epidural
      electrical stimulation of the optic nerve (ON) during surgery instead of light
      flashes. Four patients were included in this feasibility study. In 3 patients-1
      each harboring a planum sphenoidale meningioma, a tuberculum sellae meningioma,
      and an intraorbital ON sheath meningioma-2 stimulating needle electrodes were
      placed on each side of the ON just anterior to the optic canal, before unroofing
      the optic canal and an extradural anterior clinoidectomy. In the fourth patient,
      who harbored a frontotemporal astrocytoma, stimulation was applied at the exit of
      the ON from the canal. The electrically induced visual evoked potentials (eVEPs)
      were recorded from the scalp before, during, and after tumor removal. A typical
      eVEP consisted of N20 and N40 waves. The amplitude of the N40 wave varied up to
      25% prior to tumor removal. In the patient with a symptomatic tuberculum sellae
      meningioma, the decompressive effect of opening the optic canal and the impact of
      manipulation during piecemeal tumor removal were detected by the eVEPs. In the
      patient with an ON sheath meningioma and light sensation, only the N20 wave was
      observed. Epidural electrical stimulation of the ON is a safe means of providing
      a stable signal and real-time information on nerve conduction during surgery. It
      may be a useful adjunct in improving visual outcomes postoperatively. Further
      clinical studies are necessary.

PMID- 18826352
TI  - Correlation of intrinsic optical signal, cerebral blood flow, and evoked
      potentials during activation of rat somatosensory cortex.
AB  - OBJECT: This study was undertaken to test the hypothesis that cerebral blood flow
      (CBF) and the intrinsic optical signal could be dissociated by altering adenosine
      receptor activity and to uncover the origin of the optic signal using a cranial
      window in the anesthetized rat. METHODS: In anesthetized, ventilated, and
      temperature-controlled rats with closed cranial windows, the authors evaluated
      simultaneously the alterations in pial arteriolar diameter, intrinsic optical
      signals (690 nm), and somatosensory evoked potentials during cortical activation
      evoked by contralateral sciatic nerve stimulation (SNS). To dissociate the
      vascular and intrinsic signal, they topically applied the adenosine receptors
      antagonists theophylline (5 microM), which affects A1 and A2A receptors, and 8
      cyclopentyl-1,3-dipropylxanthine (CPX, 1 microM), which blocks the A(1) receptor.
      The former interacts primarily with the vasculature whereas the latter influences
      the parenchyma exclusively. RESULTS: During 20 seconds of contralateral SNS, pial
      arterioles in the hindlimb somatosensory cortex dilated in a characteristic peak
      and shoulder pattern. As compared with mock cerebrospinal fluid alone,
      theophylline significantly (p<0.05) attenuated SNS-induced vasodilation (mean+/
      standard deviation 8.1+/-2.5% vs 21.7+/-1.9%; 4 rats in each group). In contrast,
      CPX potentiated vasodilation significantly (p<0.05) during SNS (54.7+/-15.8% for
      the CPX group vs 20.1+/-1.9% for the controls; 5 rats in each group). The change
      in optical signal persisted after cessation of SNS in all the animals. Thus, the
      pattern of change of the optical signal was distinctly different from the pattern
      of changes in arteriolar diameter (which returned rapidly to baseline). Moreover,
      the optical signal during SNS was increased by 50% by theophylline and by almost
      5-fold by CPX (p<0.05). The area of change of the intrinsic signal was also
      increased by the topical application of theophylline and CPX. The somatosensory
      evoked potential recordings revealed no significant changes after theophylline
      application, but CPX caused a small diminution of the N1 wave (p<0.01).
      CONCLUSIONS: The noncongruent temporal profiles of the changes in pial arteriolar
      diameter and optical signal, imaged at 690 nm, indicate that the optical signal
      at 690 nm is not related to CBF. Alteration of adenosine receptor activity
      independently changed cortical activity, as measured by the optical signal, and
      CBF, as determined by pial arteriolar diameter. Manipulation of the adenosine
      receptor activity during increased cortical activity confirmed the temporal
      dissociation of optical signal and CBF and provided further evidence for the role
      of adenosine in regulating CBF.

PMID- 18826353
TI  - Coagulopathy and inhospital deaths in patients with acute subdural hematoma.
AB  - OBJECT: Acute subdural hematoma (SDH) is one of the most lethal forms of
      intracranial injury; several risk factors predictive of a worse outcome have been
      identified. Emerging research suggests that patients with coagulopathy and
      intracerebral hemorrhage have a worse outcome than patients without coagulopathy
      but with intracerebral hemorrhage. The authors sought to determine if such a
      relationship exists for patients with acute SDH. METHODS: The authors conducted a
      retrospective analysis of consecutive patients admitted to a neurosciences
      intensive care unit with acute SDH over a 4-year period (January 1997-December
      2001). Demographic data, laboratory values, admission source, prior functional
      status, medical comorbidities, treatments received, and discharge disposition
      were recorded, as were scores on the Acute Physiology, Age, and Chronic Health
      Evaluation III (APACHE III). Coagulopathy was defined as an internal normalized
      ratio>1.2 or a prothrombin time>or=12.7 seconds. Univariate and multivariate
      analyses were performed on 244 patients to determine factors associated with
      worse short-term outcomes. RESULTS: The authors identified 248 patients with
      acute SDH admitted to the neurointensive care unit during the study period, of
      which 244 had complete data. Most were male (61%), and the mean age of the study
      population was 71.3+/-15 years (range 20-95 years). Fifty-three patients (22%)
      had coagulopathy. The median APACHE III score was 43 (range 11-119). Twenty-nine
      patients (12%) died in the hospital. Independent predictors of inhospital death
      included APACHE III score (odds ratio [OR] 4.4, 95% confidence interval [CI] 1.4
      13.4, p=0.011) and coagulopathy (OR 2.7, 95% CI 1.1-7.1, p=0.037). Surgical
      evacuation of acute SDH was associated with reduced inhospital deaths (OR 0.2,
      95% CI 0.1-0.6, p=0.003). CONCLUSIONS: Coagulopathy is independently associated
      with inhospital death in patients with acute SDH. Time to treatment to correct
      coagulopathy using fresh frozen plasma and/or vitamin K was prolonged.

PMID- 18826354
TI  - Surface dialysis after experimental brain injury: modification of edema fluid
      flow in the rat model.
AB  - OBJECT: This study was undertaken to determine if dialysis of damaged brain
      surface can reduce cerebrospinal fluid (CSF) pressure and progressive brain
      edema. The authors secondarily determined if local brain cooling was
      simultaneously possible. METHODS: Telemetric pressure transmitters were implanted
      into the lumbar subarachnoid space of 58 young adult male rats. Cryogenic brain
      injury was created and 2 hours later decompressive craniectomy was performed. An
      osmotic cell with a semipermeable dialysis membrane placed on the damaged brain
      surface was perfused with dextran 15% solution for 2 or 4 hours. Water content
      was determined in the cerebral hemispheres using the wet-dry weight method. Evans
      blue-albumin spread was measured morphometrically. Brain temperature was measured
      bilaterally. RESULTS: The CSF pressure increased after cryogenic injury and
      decreased after craniotomy. Two hours of brain dialysis significantly reduced CSF
      pressure in comparison with craniotomy alone and sham dialysis. Injured brain had
      higher water content, but this was not affected by dialysis. Spread of Evans blue
      albumin, however, was significantly reduced by the treatment. Cooling of the
      dialysis solution caused significant local brain cooling. CONCLUSIONS: Surface
      dialysis of cryogenically injured rat brain controls CSF pressure and reduces
      intraparenchymal spread of edema fluid in the acute period after injury. The
      authors postulate that edema fluid moves into the osmotic cell rather than
      spreading through the uninjured brain. Long-term experiments will be needed to
      prove that this combination therapy is effective.

PMID- 18826355
TI  - Relationship of "dose" of intracranial hypertension to outcome in severe
      traumatic brain injury.
AB  - OBJECT: It has recently been suggested that the degree of intracranial pressure
      (ICP) above the treatment goal can be estimated by the area under the curve (AUC)
      of ICP versus time in patients with severe traumatic brain injury (TBI). The
      objective of this study was to determine whether the calculated "ICP dose"-the
      ICP AUC-is related to mortality rate, outcome, and Marshall CT classification.
      METHODS: Of 135 patients (age range 1-82 years) with severe TBI treated during a
      5-year period at the authors' institution, 113 patients underwent ICP monitoring
      (84%). Ninety-three patients with a monitoring time>24 hours were included for
      analysis of ICP AUC calculated using the trapezoidal method. Computed tomography
      scans were assessed according to the Marshall TBI classification. Patients with
      Glasgow Outcome Scale scores at 6 months and >3 years were separated into 2
      groups based on outcome. RESULTS: Sixty patients (65%) had ICP values>20 mm Hg,
      and 12 (13%) developed severe intracranial hypertension and died secondary to
      herniation. A multiple regression analysis adjusting for Glasgow Coma Scale
      score, age, pupillary abnormalities and Injury Severity Scale score demonstrated
      that the ICP AUC was a significant predictor of poor outcome at 6 months
      (p=0.034) and of death (p=0.035). However, it did not predict long-term outcome
      (p=0.157). The ICP AUC was significantly higher in patients with Marshall head
      injury Categories 3 and 4 (24 patients) than in those with Category 2 (23
      patients, p=0.025) and Category 5 (46 patients, p=0.021) TBIs using the worst CT
      scan obtained. CONCLUSIONS: The authors found a significant relationship between
      the dose of ICP, the worst Marshall CT score, and patient outcome, suggesting
      that the AUC method may be useful in refining and improving the treatment of ICP
      in patients with TBI.

PMID- 18826356
TI  - Do long-term results justify decompressive craniectomy after severe traumatic
      brain injury?
AB  - OBJECT: A decompressive craniectomy can be a life-saving procedure to relieve
      critically increased intracranial pressure. The survival of a patient is
      important as well as the subsequent and long-term quality of life. In this paper
      the authors' goal was to investigate whether long-term clinical results justify
      the use of a decompressive craniectomy. METHODS: Thirty-three patients (20 males
      and 13 females) with a mean age of 36.3 years (range 13-60 years) with severe
      traumatic brain injury (Grades III and IV) and subsequent massive brain swelling
      were examined. For postoperative assessment the Barthel Index was used. A
      surgical intervention was based on the following criteria: 1) The intracranial
      pressure could not be controlled by conservative treatment and constantly
      exceeded 30 mm Hg (cerebral perfusion pressure<50 mm Hg). 2) Transcranial Doppler
      ultrasonography revealed only a systolic flow pattern or systolic peaks. 3) There
      were no other major injuries. 4) The patient was not older than 60 years.
      RESULTS: One-fifth of all patients died and one-fifth remained in a vegetative
      state. Mild deficits were seen in 6 of 33 patients. A full rehabilitation
      (Barthel Index 90-100) was achieved in 13 patients (39.4%). Five patients could
      resume their former occupation, and another 4 had to change jobs. CONCLUSIONS:
      Age remains to be one of the most important exclusion factors. Decompressive
      craniectomy provided good clinical results in nearly 40% of patients who were
      otherwise most likely to die. Therefore, long-term results justify the use of
      decompressive craniectomy in this case series.

PMID- 18826357
TI  - Increase in phosphorylation of Akt and its downstream signaling targets and
      suppression of apoptosis by simvastatin after traumatic brain injury.
AB  - OBJECT: In their previous studies, the authors found that simvastatin treatment
      of traumatic brain injury (TBI) in rats had beneficial effects on spatial
      learning functions. In the current study they wanted to determine whether
      simvastatin suppressed neuronal cell apoptosis after TBI, and if so, they wanted
      to examine the underlying mechanisms of this process. METHODS: Saline or
      simvastatin (1 mg/kg) was administered orally to rats starting on Day 1 after TBI
      and then daily for 14 days. Modified Neurological Severity Scores were used to
      evaluate the sensory motor functional recovery. Rats were killed at 1, 3, 7, 14,
      and 35 days after treatment, and brain tissue was harvested for terminal
      deoxynucleotidyl nick-end labeling (TUNEL) staining, caspase-3 activity assay,
      and Western blot analysis. RESULTS: Simvastatin significantly decreased the
      modified Neurological Severity Scores from Days 7 to 35 after TBI, significantly
      reduced the number of TUNEL-positive cells at Day 3, suppressed the caspase-3
      activity at Days 1 and 3 after TBI, and increased phosphorylation of Akt as well
      as Forkhead transcription factor 1, inhibitory-kappaB, and endothelial nitric
      oxide synthase, which are the downstream targets of the prosurvival Akt signaling
      protein. CONCLUSIONS: These data suggested that simvastatin reduces the apoptosis
      in neuronal cells and improves the sensory motor function recovery after TBI.
      These beneficial effects of simvastatin may be mediated through activation of
      Akt, Forkhead transcription factor 1 and nuclear factor-kappaB signaling
      pathways, which suppress the activation of caspase-3 and apoptotic cell death,
      and thereby, lead to neuronal function recovery after TBI.

PMID- 18826358
TI  - Dosing and safety of cyclosporine in patients with severe brain injury.
AB  - OBJECT: Cyclosporine neuroprotection has been reported in brain injury models but
      safety and dosing guidelines have not been determined in humans with severe
      traumatic brain injury (TBI). The purpose of this investigation was to establish
      the safety of cyclosporine using 4 clinically relevant dosing schemes. METHODS:
      The authors performed a prospective, blinded, placebo-controlled, randomized,
      dose-escalation trial of cyclosporine administration initiated within 8 hours of
      TBI (Glasgow Coma Scale score range 4-8; motor score range 2-5). Four dosing
      cohorts (8 patients treated with cyclosporine and 2 receiving placebo treatment
      per cohort) received cyclosporine (1.25-5 mg/kg/day) or placebo in 2 divided
      doses (Cohorts I-III) or continuous infusion (Cohort IV) over 72 hours. Adverse
      events and outcome were monitored for 6 months. RESULTS: Forty patients were
      enrolled over 3 years (cyclosporine cohorts, 24 male and 8 female patients;
      placebo group, 8 male patients). Systemic trough concentrations were below 250
      ng/ml during intermittent doses. Higher blood concentrations were observed in
      Cohorts III and IV. There was no significant difference in immunological effects,
      adverse events, infection, renal dysfunction, or seizures. Mortality rate was not
      affected by cyclosporine administration, independent of dose, compared with
      placebo (6 of 32 patients receiving cyclosporine and 2 of 8 receiving placebo
      died, p>0.05). At 6 months, a dose-related improvement in favorable outcome was
      observed in cyclosporine-treated patients (p<0.05). CONCLUSIONS: In patients with
      acute TBI who received cyclosporine at doses up to 5 mg/kg/day, administered
      intravenously, with treatment initiated within 8 hours of injury, the rate of
      mortality or other adverse events was not significantly different from that of
      the placebo group.

PMID- 18826359
TI  - Neuroprotective effects of erythropoietin on acute metabolic and pathological
      changes in experimentally induced neurotrauma.
AB  - OBJECT: Head trauma is a dynamic process characterized by a cascade of metabolic
      and molecular events. Erythropoietin (EPO) has been shown to have neuroprotective
      effects in animal models of traumatic brain injury (TBI). Acute in vivo
      mechanisms and pathological changes associated with EPO following TBI are
      unknown. In this study the authors compare acute metabolic and pathological
      changes following TBI with and without systemically administered EPO. METHODS:
      Right frontal lobe microdialysis cannulae and right parietal lobe percussion hubs
      were inserted into 16 Sprague-Dawley rats. After a 4- to 5-day recovery, TBI was
      induced via a DragonFly fluid-percussion device at 2.5-2.8 atm. Rats were
      randomized into 2 groups, which received 5000 U/kg EPO or normal saline
      intraperitoneally 30 minutes after TBI. Microdialysis samples for glucose,
      lactate, pyruvate, and glutamate were obtained every 25 minutes for 10 hours.
      Rats were killed, their brains processed for light microscopy, and sections
      stained with H & E. RESULTS: Erythropoietin administered 30 minutes after TBI
      directly affects acute brain metabolism. Brains treated with EPO maintain higher
      levels of glucose 4-10 hours after TBI (p<0.01), lower levels of lactate 6-10
      hours after TBI (p<0.01), and lower levels of pyruvate 7.5-10 hours after TBI
      (p<0.01) compared with saline-treated controls. Erythropoietin maintains aerobic
      metabolism after TBI. Systemic EPO administration reduces acute TBI-induced
      lesion volume (p<0.05). CONCLUSIONS: Following TBI, neuron use initially
      increases, with subsequent depletion of extracellular glucose, resulting in
      increased levels of extracellular lactate and pyruvate. This energy requirement
      can result in cell death due to increased metabolic demands. These data suggest
      that the neuroprotective effect of EPO may be partially due to improved energy
      metabolism in the acute phase in this rat model of TBI.

PMID- 18826360
TI  - Brain cortex regeneration affected by scaffold architectures.
AB  - OBJECT: The aim of this study was to compare designed scaffolds with a random
      pored sponge scaffold to determine what role scaffold architecture plays in a
      cortical injury model. METHODS: Cylindrical scaffolds (3x3 mm) were made of a
      poly-(epsilon-caprolactone) polymer with 2 different molds from a 3D printer and
      had either: 1) unidirectional channels and microgrooves oriented longitudinally
      within the cylinder or 2) orthogonally intersecting channels and axial
      microgrooves within the cylinder. Additional randomized porosity was imparted
      using a salt-leaching method. A control scaffold without channels or microgrooves
      but containing random pores was also made. Scaffolds were implanted for 1, 4, and
      8 weeks in a cylindrical defect created 3 mm posterior to the bregma in rat
      cortex. Control animals had tissue removed but received no implant. Brains were
      coronally cryosectioned and sections were stained. Antibodies for nestin, glial
      fibrillary acidic protein (GFAP), and TUJ1 were used to identify neural
      progenitors, activated astrocytes, and neuronal axons. Tissue ingrowth (H & E),
      astrocytic infiltration (GFAP), parenchymal inflammation (GFAP), and defect width
      (H & E) were quantified from images. RESULTS: Defect widths grew and parenchymal
      inflammation decreased over time with no statistical difference between groups.
      Total tissue ingrowth and astrocytic infiltration increased over time and was
      greatest in the orthogonal design group. Specific cell ingrowth, which was
      aligned with microgrooves interiorly in the orthogonal group and exteriorly in
      the longitudinal channel group, was qualitatively assessed from nestin and TUJ1
      labeling. CONCLUSIONS: Scaffold architecture can benefit brain tissue
      regeneration by integrating the following design principles: 1) large (100s of
      micrometers) pores or channels oriented toward the parenchyma for increased
      astrocytic infiltration; 2) microgrooves oriented in the desired direction of
      cellular migration and neuronal alignment; and 3) fully interconnecting channels
      for cellular migration and tissue integration.

PMID- 18826361
TI  - Mesencephalic ependymal cysts: treatment under pure endoscopic or endoscope
      assisted keyhole conditions.
AB  - OBJECT: Primary intracranial ependymal cysts are extremely rare. Similar to
      congenital intraparenchymal cysts in the mesencephalon they usually occur with
      symptoms of an occlusive hydrocephalus or symptoms like Parinaud syndrome,
      dizziness, or gait disturbance. The objective of this study was to evaluate the
      surgical methods for the treatment of these cysts and the clinical outcome of the
      patients. METHODS: The authors present the clinical records of 8 patients who
      were treated in their department for symptomatic mesencephalic ependymal cysts in
      the past 10 years. The patient age ranged from 22 to 60 years with a mean age of
      44 years. In 4 cases the authors performed a suboccipital infratentorial
      supracerebellar approach by using endoscope-assisted microsurgery. The other 4
      patients underwent a pure endoscopic procedure over a frontal bur hole
      trepanation. RESULTS: Four patients became symptom free, and the remaining 4
      improved significantly after a mean follow-up duration of 38.5 months (range 5
      119 months). One patient underwent 2 operations: first a ventriculocystostomy and
      4 months later endoscopic third ventriculostomy because of recurrent
      hydrocephalus. In 1 case a second surgery was necessary because of a wound
      infection. In all of the patients an adequate fenestration of the cyst was
      achieved. CONCLUSIONS: A symptomatic mesencephalic ependymal cyst is an
      indication for neurosurgical intervention. These cysts can be treated
      successfully and most likely definitively by a pure endoscopic or endoscope
      assisted keyhole neurosurgical technique. There were no morbid conditions or
      death due to the procedures in this group of 8 patients. Therefore, the authors
      regard these surgical procedures to be good alternatives to treatments such as
      shunt placement or stereotactic aspiration of the cysts.

PMID- 18826362
TI  - Risk factors for neurosurgical site infections: an 18-month prospective survey.
AB  - OBJECT: The purpose of this study was to determine the incidence rate and risk
      factors of surgical site infections (SSIs) in neurosurgery for any type of
      surgery and any American Society of Anesthesiologists class. METHODS: The authors
      undertook an exhaustive 18-month prospective survey including patients who
      underwent neurosurgery. In particular, a 30-day follow-up was completed in
      patients whose surgery did not involve placement of a prosthesis or implant, and
      1-year follow-up was completed for patients who underwent surgery to place a
      prosthesis or implant. The Centers for Disease Control definition of SSI was
      used. Univariate and multivariate analyses were conducted; all dependent
      variables found in univariate analysis were entered in the multiple regression
      model. A stepwise multiple logistic regression method was used. RESULTS: Of the
      844 patients studied, 35 SSIs were diagnosed, yielding an incidence rate of 4.1%
      (95% confidence interval 3.6-4.5). Independent predictive risk factors for
      infection were cerebrospinal fluid leakage, external shunt, Altemeier class, and
      further neurosurgery. A lack of antibiotic prophylaxis was not found to be a risk
      factor. CONCLUSIONS: Infection risk factors occur mainly during the postoperative
      period.

PMID- 18826363
TI  - Brain biopsy in patients with suspected Creutzfeldt-Jakob disease.
AB  - OBJECT: Creutzfeldt-Jakob disease (CJD) is a rare neurodegenerative disorder with
      diagnostic criteria defined as a combination of clinical symptoms,
      electroencephalography findings, cerebrospinal fluid (CSF) analysis, and MR
      imaging results. Special subtypes are known to present with an atypical course
      and test findings that can complicate the clinical diagnosis. In such patients a
      brain biopsy can support the clinical approach. METHODS: The authors studied the
      records on 26 brain biopsies conducted in patients with suspected CJD who had
      been referred to the CJD Surveillance Unit in Germany between 1993 and 2005.
      RESULTS: Of the 26 included patients, 11 suffered from neuropathologically
      confirmed CJD, which in 5 cases had been deemed clinically "probable" and in 2
      had been deemed "possible." The disease in the remaining 4 patients had been
      categorized as "other" prior to neuropathological confirmation of CJD. The
      results of 15 brain biopsies showed no features of prion disease. None of these
      15 patients had received a probable diagnosis of CJD, 4 had a possible diagnosis,
      and 11 had received a diagnosis of "other." Three of the cases classified as
      other and none of those with CJD presented with pleocytosis in the CSF. In 73% of
      the other cases, biopsy sampling did not reveal any results characteristic of CJD
      but did not provide specific findings on which to base a differential diagnosis.
      Autopsy confirmed the biopsy diagnosis of CJD in all cases, and additionally
      confirmed that CJD was not present in 3 patients who had nondiagnostic biopsy
      results. CONCLUSIONS: Biopsy sampling may be helpful in the diagnostic approach
      to rare cases of dementia for which a reliable diagnosis cannot be established on
      the basis of clinical symptoms, CSF parameters, electroencephalography, and MR
      imaging results.

PMID- 18826364
TI  - Temporal lobectomy for refractory status epilepticus in a case of limbic
      encephalitis.
AB  - The authors report a case of status epilepticus secondary to limbic encephalitis
      that was successfully treated with temporal lobectomy. A 45-year-old woman
      presented in status epilepticus refractory to high-dose suppressive medical
      therapy. Magnetic resonance imaging of the brain showed T2- and FLAIR-weighted
      hyperintensities in the right temporal lobe, left and right frontal lobes, and
      pons. A lumbar puncture revealed normal findings. Continuous
      electroencephalography monitoring showed continued right temporal seizure
      activity. A paraneoplastic panel was positive for N-type voltage-gated calcium
      channels. Subsequent bronchial biopsy revealed small cell carcinoma of the lung.
      A right temporal lobectomy was performed due to refractory status, resulting in
      resolution of seizure activity and recovery of good neurological function. The
      authors describe their case and review the literature on surgical therapy for
      refractory status epilepticus and limbic encephalitis.

PMID- 18826365
TI  - Posterior fossa arachnoid cyst, tonsillar herniation, and syringomyelia in
      trichorhinophalangeal syndrome Type I.
AB  - The authors report the case of a patient with Chiari malformation Type I (CM-I)
      and syringomyelia probably caused by a retrocerebellar arachnoid cyst. The
      patient's phenotype corresponded to trichorhinophalangeal syndrome Type I. The
      authors attributed the origin of both the retrocerebellar cyst and the abnormal
      posterior fossa to endochondral ossification anomalies that occur in this
      syndrome. The patient's spinal pain was most likely a result of the combination
      of CM-I and syringomyelia. To the best of the authors' knowledge, this is the
      first report on the association of CM-I and syringomyelia with a retrocerebellar
      arachnoid cyst occurring in a patient with trichorhinophalangeal syndrome Type I.
      The authors discuss the pathogenetic mechanisms involved in the production of
      tonsillar descent and syringomyelia in this patient, and review the current
      literature on related conditions that can result in this association.

PMID- 18826366
TI  - Management of Cushing's disease: outcome in patients with microadenoma detected
      on pituitary magnetic resonance imaging.
AB  - OBJECT: Outcomes of therapy for Cushing's disease (CD) vary depending on
      different aspects of presentation and diagnostic studies. The authors designed
      this study to verify the remission rate and outcomes after transsphenoidal
      surgery (TSS) for patients with CD who had positive findings on MR imaging.
      METHODS: Patients who had presented with CD at the University of Virginia for
      initial treatment between July 1992 and December 2005 were retrospectively
      reviewed. The patients included in the study were considered to be optimal
      surgical candidates, defined as an adult (>18 years of age) with classic clinical
      features of CD, laboratory studies confirming a central (pituitary/hypothalamic)
      adrenocorticotropic hormone-dependent source of disease, and an MR imaging study
      revealing a microadenoma in the sella turcica. RESULTS: A total of 167 patients
      fulfilled the criteria. Thirty were men (18%) and 137 were women (82%). The mean
      age was 42.3 years (range 18.2-77 years). All patients underwent TSS. Surgical
      remission was achieved in 148 patients (88.6%), which was correlated with the
      surgeon's intraoperative identification of an adenoma (p=0.03). Histopathological
      confirmation of an adrenocorticotropic hormone-secreting adenoma strongly
      correlated with remission (p=0.0001). Three patients (1.8%) had postoperative
      cerebrospinal fluid leaks, and 1 patient had meningitis. Transient diabetes
      insipidus was diagnosed and treated in 10 patients (6%), whereas permanent
      diabetes insipidus occurred in 8 patients (4.8%). Panhypopituitarism followed the
      surgery in 14 patients (8.3%), 13 of whom underwent total hypophysectomy (9
      initially and 4 with early reoperations), and in 1 of 10 patients who underwent
      subtotal hypophysectomy. Nineteen patients (12.8%) who were initially in
      remission developed recurrent CD after an average of 50 months. The mean follow
      up for the 167 patients was 39 months (range 6-157 months). Gamma Knife surgery
      was the most common modality of radiotherapy used to treat 31 patients (18.5%)
      who did not achieve remission or later presented with recurrent disease.
      Bilateral adrenalectomies were performed in 10 patients in the series (6%), 2 of
      whom developed Nelson's syndrome. The overall posttreatment remission rate was
      95.8%. CONCLUSIONS: Even in patients with ideal diagnostic criteria of CD, there
      remain a significant number of cases in which TSS alone is not adequate to assure
      long-lasting remission. A multidisciplinary approach is essential to the
      achievement of satisfactory overall remission rates.

PMID- 18826367
TI  - Hypophysectomy for prostate cancer: a revival of old knowledge?
AB  - The growth of prostate cancer is controlled by several hormones and growth
      factors. In cases of metastasized prostate cancer, antigonadotropic therapy is
      currently considered state-of-the-art treatment. Surgical therapies such as
      adrenalectomy and hypophysectomy are no longer in use. Nevertheless,
      hypophysectomy has proven efficacy for palliative pain treatment as well as
      increasing duration of survival. The authors present the case of a 63-year-old
      man with metastatic prostate cancer who presented with high serum prostate
      specific antigen levels (1216 microg/L) and cavernous sinus syndrome. His disease
      was progressing despite leuprorelin and docetaxel therapy, and he had severe bone
      pain despite high-dose pain therapy. He was also anemic. Contrast-enhanced MR
      imaging showed a pituitary lesion as well as metastatic infiltration of the skull
      base including the cavernous sinus. The patient's serum level of prolactin was
      mildly elevated, testosterone was below the detection limit, and insulin-like
      growth factor-I (IGF-I) was in the upper range for a patient of his age (233
      microg/L). Because of the elevated prolactin and high-normal IGF-I levels he was
      offered a hypophysectomy in addition to pituitary tumor removal. Histological
      examination of the resected lesion confirmed a nonsecreting pituitary adenoma
      with infiltration of prostate cancer cells. Postoperatively the patient's
      prostate-specific antigen levels dropped to 876 microg/L, his bone pain resolved,
      and the cavernous sinus syndrome improved. Nevertheless, he died of septicemia 4
      months after surgery. Older publications as well as this case have shown the
      benefit of hypophysectomy for pain treatment. A reduction of IGF-I levels even in
      the final stage metastasized prostate cancer may play a major role. Respectively,
      clinical studies with somatostatin analogs are currently in progress, which may
      lead to a "new" way of treatment in these otherwise hopeless patients. On the
      basis of the pain relief seen after hypophysectomy in this case and similar
      benefits reported in older publications, the authors raise the question whether
      this treatment should be offered more frequently, and whether additional medical
      options of hormone treatment may be beneficial in similar cases.

PMID- 18826368
TI  - The legendary contributions of Thomas Willis (1621-1675): the arterial circle and
      beyond.
AB  - Thomas Willis established neurology as a distinct discipline and made significant
      original contributions to many related fields including anatomy, pathology,
      cardiology, endocrinology, and gastroenterology. He is most remembered for his
      work in elucidating the function and anatomy of the circle of Willis. Willis'
      accomplishments and research methods can be credited in large part to his
      unconventional medical education which did not include traditional teachings, but
      rather emphasized learning through clinical practice. Although Willis was not the
      first to describe the arterial circle, he was the first to describe its function
      and provide a complete, undisputed illustration through his own innovative use of
      dye studies. The Willis classification of cranial nerves was still in use over
      100 years after its original description. He has also described several disease
      entities and named many brain structures. Willis' accomplishments in comparative
      anatomy and understanding the pathophysiology of various diseases through
      original multidisciplinary experimental work in a clinical setting reveal that he
      was a true pioneer in translational research.

PMID- 18826369
TI  - Cocaine and aneurysms.

PMID- 18826370
TI  - Long-term serial passage and neuronal differentiation capability of human bone
      marrow mesenchymal stem cells.
AB  - The development of methods to induce differentiation of human mesenchymal stem
      cells (hMSCs) has opened the possibility of using these cells in regenerative or
      reparative therapies. However, the low frequency of hMSCs in tissue means it is
      often necessary to expand these cells extensively in vitro. In this study, we
      evaluated the effects of long-term serial passage on the characteristics of bone
      marrow-derived hMSC populations. In addition, we examined the effect on
      subsequent hMSC neural differentiation ability, which has not been reported
      earlier. The hMSC population examined was found to maintain a stable phenotype
      during the first 6-8 passages of culture as assessed by proliferative ability,
      morphological appearance, and surface antigen, gene and protein expression, and
      also expressed pluripotency and neural lineage markers constitutively in the
      undifferentiated state. Long-term subcultivation neither resulted in spontaneous
      neural differentiation nor compromised the ability of hMSCs to develop toward an
      early neuronal fate. In addition, the transformation elicited in hMSC cultures in
      response to cytokine-based neuronal differentiation was examined by live cell
      microscopy. We demonstrated, for the first time, that the observed changes result
      from active and dynamic processes involving outgrowth and motility of cellular
      extensions, processes entirely distinct from the rapid epiphenomena of
      cytotoxicity and cytoskeleton disruption generated by chemical induction methods.
      Cytokine-induced differentiation of hMSCs was also associated with upregulation
      of early neural gene and protein expression. These findings support the neuronal
      differentiation capability of hMSCs, although further investigation is required
      to confirm the ability to attain a mature neuronal phenotype.

PMID- 18826371
TI  - Climate change trade-offs in the side-blotched lizard (Uta stansburiana): effects
      of growing-season length and mild temperatures on winter survival.
AB  - An expanding body of literature has demonstrated that global climate change
      continues to adversely affect many populations, species, and ecosystems. However,
      life-history theory also predicts possible benefits from longer growing seasons
      and less severe winters, particularly for ectotherms. To test the idea that
      climate change will have benefits as well as costs, I studied the impacts of
      growing-season length on growth and overwintering conditions on survival time
      using side-blotched lizards (Uta stansburiana). Experiments in replicate field
      enclosures revealed that fall growing-season length has a direct effect on
      overwintering body size. Laboratory experiments revealed that both size and
      overwintering temperature have direct effects on winter survival time. Larger
      lizards are more likely to survive longer regardless of winter temperature.
      Furthermore, animals in colder (but still mild) winter microenvironments are more
      likely to survive longer than those in warmer winter environments. These results
      indicate that warmer winters caused by global climate change have the potential
      to negatively affect ectotherm populations. However, longer growing seasons may
      offset losses by allowing additional growth and energy storage. Thus,
      environmental alterations associated with climate change may be simultaneously
      beneficial and detrimental, and the long-term persistence of certain organisms
      may depend on the relative strength of their effects.

PMID- 18826372
TI  - Prolongation of hospital stay and additional costs due to nosocomial bloodstream
      infection in an Algerian neonatal care unit.
AB  - BACKGROUND: Previous studies from developed countries reported that nosocomial
      bloodstream infection (BSI) in neonatal care units (NCUs) increases length of
      stay and costs. However, no such information is available for Algerian NCUs.
      OBJECTIVE: To evaluate the influence of BSI in neonates on additional charges and
      length of hospital stay. DESIGN: Prospective, nested case-control study. SETTING:
      The 47-bed NCU of the University Hospital of Blida, Algeria. PATIENTS AND
      METHODS: A total of 83 neonates with BSIs (case patients) and 166 neonates
      without BSIs (control patients), admitted to the NCU during the study period
      (April 2004 through December 2007), were matched for sex, birth weight, length of
      NCU stay, and year of hospital admission. Each patient's length of stay in the
      NCU was obtained prospectively on daily rounds. The estimated cost of each NCU
      day was provided by the hospital's finance department. The cost of antibiotics
      prescribed was provided by the hospital's pharmacy department. RESULTS: The mean
      additional length of NCU stay for case patients, compared with control patients,
      was 9.2 days (24.3 vs 15.1 days). The mean additional cost of antibiotics was
      dollars 546. The mean cumulative additional cost was dollars 1,315. CONCLUSION:
      This study highlights the effect of BSI on extra costs for NCU patients,
      especially costs due to prolongation of hospital stay and increased antibiotic
      use, and suggests that NCUs in Algeria have a financial interest in reducing the
      rate of BSI.

PMID- 18826373
TI  - Herpes zoster with skin lesions and meningitis caused by 2 different genotypes of
      the Oka varicella-zoster virus vaccine.
AB  - A previously healthy boy who had received varicella vaccine developed herpes
      zoster with meningitis. The vaccine strain recovered from scabs of 3 skin lesions
      had the wild-type allele at position 108111, a vaccine marker never previously
      associated with vaccine-associated adverse events. The vaccine strain from
      cerebrospinal fluid also contained mutations never previously observed at vaccine
      associated single nucleotide polymorphisms that would alter amino acid sequences
      in ORF54 and ORF59. The presence of distinct strains in skin lesions and
      cerebrospinal fluid indicate that >1 variant strain may reactivate to cause
      herpes zoster.

PMID- 18826374
TI  - Phagocytosis: a repertoire of receptors and Ca(2+) as a key second messenger.
AB  - Receptor-mediated phagocytosis is a complex process that mediates the
      internalization, by a cell, of other cells and large particles; this is an
      important physiological event not only in mammals, but in a wide diversity of
      organisms. Of simple unicellular organisms that use phagocytosis to extract
      nutrients, to complex metazoans in which phagocytosis is essential for the innate
      defence system, as a first line of defence against invading pathogens, as well as
      for the clearance of damaged, dying or dead cells. Evolution has armed
      multicellular organisms with a range of receptors expressed on many cells that
      serve as the molecular basis to bring about phagocytosis, regardless of the
      organism or the specific physiological event concerned. Key to all phagocytic
      processes is the finely controlled rearrangement of the actin cytoskeleton, in
      which Ca(2+) signals play a major role. Ca(2+) is involved in cytoskeletal
      changes by affecting the actions of a number of contractile proteins, as well as
      being a cofactor for the activation of a number of intracellular signalling
      molecules, which are known to play important roles during the initiation,
      progression and resolution of the phagocytic process. In mammals, the requirement
      of Ca(2+) for the initial steps in phagocytosis, and the subsequent phagosome
      maturation, can be quite different depending on the type of cell and on the type
      of receptor that is driving phagocytosis. In this review we discuss the different
      receptors that mediate professional and non-professional phagocytosis, and
      discuss the role of Ca(2+) in the different steps of this complex process.

PMID- 18826375
TI  - Histidine-regulated activity of M-ficolin.
AB  - Human M-ficolin is a pathogen-associated molecular recognition molecule in the
      innate immune system, and it binds to some sugars, such as GlcNAc (N
      acetylglucosamine), on pathogen surfaces. From previous structural and functional
      studies of the FD1 (M-ficolin fibrinogen-like domain), we proposed that the
      ligand-binding region of FD1 exists in a conformational equilibrium between
      active and non-active states depending on three groups with a pK(a) of 6.2, which
      are probably histidine residues, and suggested that the 2-state conformational
      equilibrium as well as the trimer formation contributes to the discrimination
      mechanism between self and non-self of FD1 [Tanio, M., Kondo, S., Sugio, S. and
      Kohno, T. (2007) J. Biol. Chem. 282, 3889-3895]. To investigate the origins of
      the pH dependency, mutational analyses were performed on FD1 expressed by
      Brevibacillus choshinensis. The GlcNAc binding study of a series of single
      histidine mutants of FD1 demonstrated that His(251), His(284) and His(297) are
      required for the activity, and thus we concluded that the three histidines are
      the origins of the pH dependency of FD1. Monomeric mutants of FD1 show weaker
      affinity for the ligand than the trimeric wild-type, indicating that trimer
      formation confers high avidity for the ligand. In addition, analyses of the
      GlcNAc association and dissociation of FD1 provided evidence that FD1 always
      exchanges between the active and non-active states with the pH-dependent
      populations in solution. The biological roles of the histidine-regulated
      conformational equilibrium of M-ficolin are discussed in terms of the self and
      non-self discrimination mechanism.

PMID- 18826376
TI  - Failure to up-regulate VEGF165b in maternal plasma is a first trimester
      predictive marker for pre-eclampsia.
AB  - Pre-eclampsia is a pregnancy-related condition characterized by hypertension,
      proteinuria and endothelial dysfunction. VEGF(165)b, formed by alternative
      splicing of VEGF (vascular endothelial growth factor) pre-mRNA, inhibits
      VEGF(165)-mediated vasodilation and angiogenesis, but has not been quantified in
      pregnancy. ELISAs were used to measure means+/-S.E.M. plasma VEGF(165)b, sEng
      (soluble endoglin) and sFlt-1 (soluble fms-like tyrosine kinase-1). At 12 weeks
      of gestation, the plasma VEGF(165)b concentration was significantly up-regulated
      in plasma from women who maintained normal blood pressure throughout their
      pregnancy (normotensive group, 4.90+/-1.6 ng/ml; P<0.01, as determined using a
      Mann-Whitney U test) compared with non-pregnant women (0.40+/-0.22 ng/ml). In
      contrast, in patients who later developed pre-eclampsia, VEGF(165)b levels were
      lower than in the normotensive group (0.467+/-0.209 ng/ml), but were no greater
      than non-pregnant women. At term, plasma VEGF(165)b concentrations were greater
      than normal in both pre-eclamptic (3.75+/-2.24 ng/ml) and normotensive (10.58
      ng/ml+/-3.74 ng/ml; P>0.1 compared with pre-eclampsia) pregnancies. Patients with
      a lower than median plasma VEGF(165)b at 12 weeks had elevated sFlt-1 and sEng
      pre-delivery. Concentrations of sFlt-1 (1.20+/-0.07 and 1.27+/-0.18 ng/ml) and
      sEng (4.4+/-0.18 and 4.1+/-0.5 ng/ml) were similar at 12 weeks of gestation in
      the normotensive and pre-eclamptic groups respectively. Plasma VEGF(165)b levels
      were elevated in pregnancy, but this increase is delayed in women that
      subsequently develop pre-eclampsia. In conclusion, low VEGF(165)b may therefore
      be a clinically useful first trimester plasma marker for increased risk of pre
      eclampsia.

PMID- 18826377
TI  - Oral manifestations of eating disorders: a critical review.
AB  - BACKGROUND: Eating disorders (ED) are a group of psychopathological disorders
      affecting patient relationship with food and her/his own body, which manifests
      through distorted or chaotic eating behavior; they include anorexia nervosa,
      bulimia nervosa and ED not otherwise specified and may be burdened with life
      threatening complications. As oral manifestations of ED can occur in many phases
      of disease progression, they play a significant role in assessment,
      characterization and prognosis of ED. METHODS: Mucosal, dental, and salivary
      abnormalities associated with ED have been reviewed. Relations between oral
      menifestations and pathogenesis, management and prognosis of ED have been
      critically analysed. RESULTS: Oral manifestations of ED include a number of signs
      and symptoms involving oral mucosa, teeth, periodontium, salivary glands and
      perioral tissues; differences exist between patients with anorexia and bulimia.
      Oral manifestations of ED are caused by a number of factors including nutritional
      deficiencies and consequent metabolic impairment, poor personal hygiene, drugs,
      modified nutritional habits and underlying psychological disturbances.
      CONCLUSION: Oral manifestations of ED can cause impairment of oral function, oral
      discomfort and pain, and an overall deterioration of aesthetics and quality of
      life. Their treatment can contribute to overall patient management and prognosis.

PMID- 18826378
TI  - Hyptis pectinata essential oil: chemical composition and anti-Streptococcus
      mutans activity.
AB  - OBJECTIVES: The aim of the present study was to evaluate the anti-Streptococcus
      mutans activity of Hyptis pectinata essential oil, and present its promising
      potential against oral diseases. MATERIALS AND METHODS: The essential oil of H.
      pectinata was obtained by hydrodistillation from dried leaves and analyzed by GC
      / MS. The effectiveness of this essential oil regarding the antimicrobial
      activity against several S. mutans strains was investigated by the agar diffusion
      and microdilution methods, and chlorohexidine was used as a standard control.
      RESULTS: The H. pectinata essential oil exhibited considerable inhibitory effect
      against either all the clinical isolates obtained from patients' saliva or the
      ATCC strains tested, with minimum inhibitory and bactericidal concentrations of
      200 microg ml(-1). The study also compared the efficiency of the emulsifying
      agents Tween 20, Tween 80, dimethyl sulfoxide and propylene glycol in H.
      pectinata essential oil when tested against S. mutans. The data obtained
      confirmed the better inhibitory effect of the oil when using all tested diluents,
      although Tween 80 seemed to be more suitable for emulsification. CONCLUSION:
      According to our results, H. pectinata essential oil can be considered a
      promising alternative to chlorhexidine for the control of oral bacteria-related
      diseases and hygiene.

PMID- 18826379
TI  - Salivary free radical-scavenging activity is affected by physical and mental
      activities.
AB  - OBJECTIVE AND DESIGN: Free radicals/reactive oxygen species (ROS) are related to
      inflammation, aging, and cancer. However, living systems have essential
      antioxidant mechanisms by which these harmful radicals can be scavenged, i.e.,
      free radical-scavenging activity (FRSA). We measured the circadian rhythm of such
      activities by detecting salivary FRSA in healthy adults, and also examined how
      salivary FRSA is affected by physical and mental activities, which included (1)
      ingestion of beverage, (2) exercise, (3) comfortable/uncomfortable stimulation,
      and (4) smoking. METHODS: FRSA was determined by using the DPPH (1,1'-diphenyl-2
      picrylhydrazyl) method. Statistical analysis for experimentally obtained median
      values was carried out using the Wilcoxon signed rank test. RESULTS: In circadian
      rhythm, FRSA was increased by food ingestion and relaxation. As to the individual
      activities, green tea and coffee ingestion increased FRSA, whereas swimming (P <
      0.05) and dance lessons (P < 0.01) decreased it. Watching an amusing video
      program (P < 0.001) or stimulation by a pleasant aroma (P < 0.01) increased FRSA.
      In contrast, an unpleasant odor had no effect on FRSA. FRSA decreased immediately
      after smoking (P < 0.05), but increased thereafter (P < 0.01). CONCLUSION:
      Salivary FRSA was affected not only by physical activities, but also by mental
      activities. It may be a parameter for reflecting the health status of
      individuals.

PMID- 18826380
TI  - Prevalence of oral disease among adults with primary HIV infection.
AB  - OBJECTIVE: To explore the type and prevalence of oral mucosal lesions among
      adults with primary HIV infection (PHI) compared with HIV-negative adults at high
      risk for HIV disease, and in relation to HIV viral load. METHODS: We conducted
      standardized oral examinations to identify specific oral mucosal lesions among
      adults with PHI, both pre-seroconversion and post- seroconversion-recently
      infected, compared with HIV-negative adults. We compared the group with oral
      lesions to those without oral lesions with respect to HIV-RNA load and CD4 + T
      cell count. RESULTS: Among 115 adults (predominantly men), pseudomembranous
      candidiasis was the most common oral lesion among those with PHI, and was found
      in 4% of the 23 participants in pre-seroconversion and in 9% of 69 participants
      with post-seroconversion recent infection, compared with none found among 23 HIV
      negatives. Among those with PHI, the median viral load was higher and the median
      CD4 + T-cell count lower among the 15 participants with an oral lesion of any
      type than among the 77 participants without oral lesions (P = 0.02 and 0.04,
      respectively). CONCLUSION: This finding suggests that individuals with PHI who
      have oral lesions may be more likely to transmit HIV because of their higher
      viral load.

PMID- 18826381
TI  - Differential gene expression profiles of normal human parotid and submandibular
      glands.
AB  - BACKGROUND: Parotid and submandibular glands have different properties including
      characteristics of the secreted saliva and tumor incidences. The differences in
      properties of parotid and submandibular glands are not clear from a genetic
      viewpoint. OBJECTIVE: To study differential gene expression profiles between
      normal human parotid and submandibular glands. MATERIALS AND METHODS: Three pairs
      of normal parotid and submandibular glands were obtained. RNA was extracted from
      these samples. After reverse transcription, the cDNA was in vitro-transcribed to
      produce biotin-labeled cRNA. The purified biotin-labeled cRNA samples were
      hybridized to microarray chips. RESULTS: Among the 54 675 tested transcripts, 47
      transcripts were upregulated at least twofold in the parotid gland compared with
      the submandibular gland, including tumor-associated genes (pleiotrophin, WNT5A,
      ABCC1) and transport-associated genes (SLCO1A2, SLC13A5, KCNJ15). Ninety-eight
      transcripts were upregulated at least twofold in the submandibular gland compared
      with the parotid gland, including the chloride channel CFTR and mucin-associated
      genes that belong to the starch and sucrose metabolism pathway (GalNAc-T4, GalNAc
      T7 and GalNAc-T13). Quantitative real-time reverse transcriptase-polymerase chain
      reaction (RT-PCR) analysis of nine differentially expressed genes confirmed the
      microarray results. CONCLUSION: This study revealed the different gene expression
      profiles of normal human parotid and submandibular glands, providing a genetic
      basis for their differing properties.

PMID- 18826382
TI  - Immunohistochemical study of GLUT-1 in oral peripheral nerve sheath tumors.
AB  - AIM: To investigate the immunoexpression and diagnostic applicability of human
      erythrocyte-type glucose transporter protein (GLUT-1) in oral peripheral nerve
      sheath tumors. MATERIAL AND METHODS: Specimens diagnosed as oral peripheral nerve
      sheath tumors archived in the Oral Pathology Service of Universidade Federal de
      Minas Gerais from 1966 to 2006 were evaluated. Thirty-four lesions were included:
      15 traumatic neuromas, 11 neurofibromas, four neurilemmomas, and four malignant
      peripheral nerve sheath tumors (MPNST). One case of neurofibroma was associated
      with neurofibromatosis type I. Immunohistochemistry for S-100 and GLUT-1 was
      performed. S-100 was immunopositive in all lesions. RESULTS: Benign lesions were
      immunopositive for GLUT-1 except in two (18.2%) cases of neurofibromas. In the
      traumatic neuroma, the perineuriums were immunopositive for GLUT-1. In the
      neurofibroma, the immunoreactivity was heterogeneous. Immunopositivity was
      observed at levels of 54.5% in the periphery of the lesion, 9.1% in the center,
      and 18.2% in both. The neurilemmoma demonstrated immunopositivity in the capsule.
      One case (25%) of MPNST presented GLUT-1 positive stain in occasional cells
      distributed homogeneously in all the tumor area. CONCLUSION: GLUT-1 is a useful
      marker for perineurial cells and should be included in the oral peripheral nerve
      sheath tumors immunophenotyping thus aiding in the correct diagnosis of these
      lesions.

PMID- 18826383
TI  - SAA and PLTP activity in plasma of periodontal patients before and after full
      mouth tooth extraction.
AB  - OBJECTIVE: To assess whether treatment of advanced periodontal disease affects
      plasma levels of serum amyloid A (SAA) and phospholipid transfer protein (PLTP)
      activity. DESIGN: We measured the levels of SAA and PLTP activity in plasma of 66
      patients with advanced periodontal disease before and after treatment by full
      mouth tooth extraction (FME). RESULTS: At baseline, median SAA levels in our
      study population were within the normal range (2.7 microg ml(-1)) but SAA was
      elevated (>5 microg ml(-1)) in 18% of periodontitis patients. Three months after
      FME, SAA levels were significantly reduced (P = 0.04). SAA did not correlate with
      any of the periodontal disease parameters. PLTP activity was elevated in patients
      with periodontitis, compared to the PLTP activity reference group (age-matched
      systemically healthy adults, n = 29; 18 micromol ml(-1) h(-1)vs 13 micromol ml(
      1) h(-1), respectively, P = 0.002). PLTP activity inversely correlated with
      average periodontal pocket depth (PPD) per tooth (r(s) = -0.372; P = 0.002).
      Three months after FME, median PLTP activity did not change significantly.
      CONCLUSIONS: Full-mouth tooth extraction significantly reduces SAA, a marker of
      inflammation, while it does not affect plasma PLTP activity. However, the inverse
      correlation between PLTP activity and average PPD suggests that increased PLTP
      activity may limit periodontal tissue damage.

PMID- 18826384
TI  - Immunohistochemical detection of BH3-only proteins in ameloblastic tumors.
AB  - OBJECTIVE: To evaluate expression of BH3-only proteins in odontogenic tumors,
      expression of Bid, Bim, Bad, Noxa, and Puma was analyzed in ameloblastic tumors
      as well as in tooth germs. METHODS: Nine tooth germs, 37 ameloblastomas, and five
      malignant ameloblastic tumors were examined immunohistochemically with antibodies
      against Bid, Bim, Bad, Noxa, and Puma. RESULTS: Immunohistochemical reactivity
      for Bid, Bim, Bad, Noxa, and Puma was detected in the cytoplasm of cellular
      components in normal and neoplastic odontogenic tissues. Expression of these BH3
      only proteins was evident in odontogenic epithelial cells near the basement
      membrane in tooth germs and ameloblastic tumors. Acanthomatous ameloblastomas
      showed no reactivity for Bid, Bim, Bad, Noxa, or Puma in keratinizing cells,
      whereas granular cells in granular cell ameloblastomas reacted with these BH3
      only proteins. Basal and desmoplastic ameloblastomas and ameloblastic carcinomas
      showed immunoreactivity for the BH3-only proteins in most neoplastic cells.
      CONCLUSION: Expression of Bid, Bim, Bad, Noxa, and Puma in tooth germs and
      ameloblastic tumors suggests that the BH3-only proteins have a role in apoptotic
      cell death of normal and neoplastic odontogenic epithelium. Distinctive
      expression patterns of these BH3-only proteins in ameloblastoma variants suggest
      that the BH3-only proteins might be involved in tumor cell differentiation of
      ameloblastomas.

PMID- 18826385
TI  - Expression and alterations of the PTEN / AKT / mTOR pathway in ameloblastomas.
AB  - OBJECTIVES: Recently, an allelic loss of phosphatase and tensin homologue (PTEN)
      was shown to occur in ameloblastomas. In carcinogenesis, loss of PTEN allows for
      overactivity of the phosphatidylinositol-3-kinase/protein kinase B (PI3K / AKT)
      pathway inducing an upregulation of mammalian-target of rapamycin (mTOR) and its
      downstream effector ribosomal-subunit-6 kinase (S6K); allowing for uncontrolled
      cell proliferation, apoptosis inhibition and cell cycle deregulation. METHODS:
      Thirty ameloblastomas and five dental follicles were studied, looking at the
      immunohistochemical expression of total PTEN and AKT, as well as their
      phosphorylated (p) active forms, and the downstream effector and indicator of
      mTOR activity p70 ribosomal-subunit-6 kinase (pS6K). Also assessed was the
      expression of extracellular-signal-regulated kinase (ERK), which cross talks with
      AKT. RESULTS: Total PTEN was absent in 33.3% of ameloblastomas, while its
      stabilized, phosphorylated(ser380 / thr382 / thr383) form was absent in 83.3% of
      tumors. In contrast, AKT was expressed in 83.3% of ameloblastomas, showing high
      expression of the p-thr(308)AKT and p-ser(473) AKT forms in 93.3% and 56.6% of
      cases, respectively. Further, the mTOR activated pS6K(ser240 / 244) was detected
      in 86.7% of ameloblastomas, while ERK was overexpressed in 70.0% of the cases.
      CONCLUSION: Immunohistochemical analysis of aberrant signaling in the
      PI3K/AKT/mTOR pathway in ameloblastomas may represent a valuable tool for
      elucidating pathogenesis, aggressiveness and selecting optimal therapeutics.

PMID- 18826386
TI  - Changes in the immature platelet fraction within ageing platelet concentrates.

PMID- 18826387
TI  - Anticoagulant characteristics of HD1-22, a bivalent aptamer that specifically
      inhibits thrombin and prothrombinase.
AB  - BACKGROUND: HD1-22 is a bivalent aptamer that binds to thrombin with high
      affinity (K(d) = 0.65 nm) and occupies both anion binding exosites without
      blocking the active centre of the enzyme. HD1-22 has been developed by connecting
      the exosite 1 binding aptamer HD1 and the exosite 2 binding aptamer HD22 through
      a poly-dA linker. OBJECTIVES: To characterize the anticoagulant profile of HD1-22
      in comparison to the clinically established direct acting thrombin inhibitors
      bivalirudin and argatroban, and to test the efficacy of antidote
      oligodeoxynucleotides. METHODS AND RESULTS: HD1-22 prolongs clotting times of the
      thrombin time, activated partial thromboplastin time, ecarin clotting time, and
      lag-time of the tissue factor triggered thrombin generation assay in a dose
      dependent manner. On a molar basis, its anticoagulant activity was nearly
      identical to bivalirudin and superior to argatroban. Thrombin-induced platelet
      aggregation was more effectively inhibited by HD1-22 than by bivalirudin. The HD1
      22 aptamer retains the ability of the HD1-moiety to bind to (pro)exosite 1 of
      prothrombin and inhibits the prothrombinase activity nearly 2-fold better than
      HD1. The anticoagulant activities of HD1-22 are fully reversed by addition of
      antidote-oligodeoxynucleotides. CONCLUSIONS: The strong thrombin-inhibiting
      activity, together with the availability of a rapid acting antidote strategy,
      makes HD1-22 an interesting anticoagulant candidate, especially for use in
      clinical situations where effective anticoagulation and rapid reversal of the
      anticoagulant effect are required. The data obtained warrant further clinical
      studies.

PMID- 18826388
TI  - Splenic macrophages maintain the anti-platelet autoimmune response via uptake of
      opsonized platelets in patients with immune thrombocytopenic purpura.
AB  - BACKGROUND: Immune thrombocytopenic purpura (ITP) is an autoimmune disease
      primarily caused by IgG anti-platelet autoantibodies. Activation of autoreactive
      CD4(+) T cells upon recognition of cryptic GPIIb/IIIa peptides presented by
      antigen-presenting cells (APCs) is a critical step for triggering and maintaining
      the pathogenic anti-platelet autoantibody response. OBJECTIVES: We investigated
      which APCs carry the cryptic peptides of GPIIb/IIIa that activate autoreactive
      CD4(+) T cells in ITP patients. METHODS: GPIIb/IIIa-reactive T-cell lines
      generated from ITP patients were cultured with autologous freshly isolated
      splenic macrophages, B cells or dendritic cells. To further investigate how the
      macrophages presented the antigenic GPIIb/IIIa peptides, we prepared macrophages
      from the peripheral blood monocytes of the same patients during remission.
      RESULTS: Macrophages induced the proliferation of GPIIb/IIIa-reactive T-cell
      lines without an exogenous antigen, but B cells and dendritic cells required
      GPIIb/IIIa peptides to stimulate the T cells. Macrophages derived from peripheral
      blood during remission required an exogenous antigen to induce the GPIIb/IIIa
      reactive T-cell line response, but could elicit a response without added antigen
      if they were preincubated with platelets from ITP patients with platelet
      associated anti-GPIIb/IIIa antibodies or healthy platelets pretreated with ITP
      platelet eluates. The T-cell response was inhibited by anti-FcgammaRI antibody.
      Finally, cultured macrophages that captured opsonized platelets promoted anti
      GPIIb/IIIa antibody production in mixed cultures of autologous GPIIb/IIIa
      reactive T-cell lines and B cells. CONCLUSIONS: Splenic macrophages that take up
      opsonized platelets via FcgammaRI are major APCs for cryptic GPIIb/IIIa peptides,
      and are central to the maintenance of anti-platelet autoantibody production in
      ITP patients.

PMID- 18826389
TI  - Mitogen-activated protein kinases in hemostasis and  thrombosis.
AB  - The mitogen-activated protein (MAP) kinases ERK2, p38 and JNK1 are present in
      platelets and are activated by various stimuli, such as thrombin, collagen, von
      Willebrand factor (VWF) and ADP. Until recently, MAP kinases were only studied in
      the conventional model of agonist-induced platelet aggregation mediated by
      fibrinogen and integrin alphaIIbbeta3. However, this approach is likely to be too
      limited for a physiological understanding of platelet MAP kinases and their
      signaling pathways. Recent studies with varying blood-flow conditions and animal
      models of thrombosis have provided deeper insight into the role of MAP kinases in
      thrombus formation and the dependence of these kinases on shear conditions. This
      review summarizes and discusses the physiological functions of these kinases in
      hemostasis and thrombosis as revealed by various technical approaches.

PMID- 18826390
TI  - Some hemostasis variables at the end of the population distributions are risk
      factors for severe postpartum hemorrhages.
AB  - BACKGROUND: Severe postpartum hemorrhages (PPH) represent a significant cause of
      maternal morbidity/mortality, but little is known about its hemostasis-related
      risk factors. Among the 32 463 women enrolled in the NOHA First cohort, 317
      developed severe PPH (S-PPH group), 1269 non-severe PPH (NS-PPH group) and the
      remaining individuals were considered as control women (C group). METHODS: We
      performed a case-control study, including 317 triplets of women allocated from
      the three groups that shared the same clinical characteristics as the S-PPH
      group. RESULTS: From values obtained 6-9 months after delivery, low (but not
      deficient) levels of fibrinogen, von Willebrand factor (VWF) antigen, factor (F)
      XI, platelet CD42b, TRAP-induced increase of platelet CD41a and high values of
      serum residual prothrombin activity or closure aperture times using the collagen
      ADP cartridge on the PFA-100 system, and blood group O, were independently
      associated with a significant risk of severe PPH. Being positive for at least two
      of these eight variables was found in 1.6%, 3.5% and 20.8% of the women from the
      C, the NS-PPH and the S-PPH groups, respectively, the odds ratio for S-PPH in
      such a case being 16.4, 95%CI (6.5-41), P < 0.0001. CONCLUSIONS: Women with some
      hemostasis-related variables at the low or high end of the population
      distributions are prone to the severe forms of PPH. Clinical trials will allow us
      to know if acting on these risk factors can lower the clinical severity of PPH.

PMID- 18826391
TI  - Collagen-mimetic peptides mediate flow-dependent thrombus formation by high- or
      low-affinity binding of integrin alpha2beta1 and glycoprotein VI.
AB  - BACKGROUND: Collagen acts as a potent surface for platelet adhesion and thrombus
      formation under conditions of blood flow. Studies using collagen-derived triple
      helical peptides have identified the GXX'GER motif as an adhesive ligand for
      platelet integrin alpha2beta1, and (GPO)(n) as a binding sequence for the
      signaling collagen receptor, glycoprotein VI (GPVI). OBJECTIVE: The potency was
      investigated of triple-helical peptides, consisting of GXX'GER sequences within
      (GPO)(n) or (GPP)(n) motifs, to support flow-dependent thrombus formation.
      RESULTS: At a high-shear rate, immobilized peptides containing both the high
      affinity alpha2beta1-binding motif GFOGER and the (GPO)(n) motif supported
      platelet aggregation and procoagulant activity, even in the absence of von
      Willebrand factor (VWF). With peptides containing only one of these motifs, co
      immobilized VWF was needed for thrombus formation. The (GPO)(n) but not the
      (GPP)(n) sequence induced GPVI-dependent platelet aggregation and procoagulant
      activity. Peptides with intermediate affinity (GLSGER, GMOGER) or low-affinity
      (GASGER, GAOGER) alpha2beta1-binding motifs formed procoagulant thrombi only if
      both (GPO)(n) and VWF were present. At a low-shear rate, immobilized peptides
      with high- or low-affinity alpha2beta1-binding motifs mediated formation of
      thrombi with procoagulant platelets only in combination with (GPO)(n).
      CONCLUSIONS: Triple-helical peptides with specific receptor-binding motifs mimic
      the properties of native collagen I in thrombus formation by binding to both
      platelet collagen receptors. At a high-shear rate, either GPIb or high-affinity
      (but not low-affinity) GXX'GER mediates GPVI-dependent formation of procoagulant
      thrombi. By extension, high-affinity binding for alpha2beta1 can control the
      overall platelet-adhesive activity of native collagens.

PMID- 18826392
TI  - Differential roles for the adapters Gads and LAT in platelet activation by GPVI
      and CLEC-2.
AB  - BACKGROUND: The adapter proteins SLP-76 and LAT have been shown to play critical
      roles in the activation of PLCgamma2 in platelets downstream of GPVI/FcRgamma and
      the C-type lectin receptor CLEC-2. SLP-76 is constitutively associated with the
      adapter Gads in platelets, which also binds to tyrosine phosphorylated LAT,
      thereby providing a potential pathway of regulation of SLP-76. OBJECTIVE: In the
      present study, we have compared the role of Gads alongside that of LAT following
      activation of the major platelet glycoprotein receptors using mice deficient in
      the two adapter proteins. RESULTS: Gads was found to be required for the
      efficient onset of aggregation and secretion in response to submaximal
      stimulation of GPVI and CLEC-2, but to be dispensable for activation following
      stronger stimulation of the two receptors. Gads was also dispensable for
      spreading induced through integrin alpha(IIb)beta(3) or the GPIb-IX-V complex.
      Further, Gads plays a negligible role in aggregate formation on collagen at an
      arteriolar rate of shear. In stark contrast, platelets deficient in the adapter
      LAT exhibit a marked decrease in aggregation and secretion following activation
      of GPVI and CLEC-2, and are unable to form stable aggregates on collagen at
      arteriolar shear. CONCLUSIONS: The results demonstrate that Gads plays a key role
      in linking the adapter LAT to SLP-76 in response to weak activation of GPVI and
      CLEC-2 whereas LAT is required for full activation over a wider range of agonist
      concentrations. These results reveal the presence of a Gads-independent pathway
      of platelet activation downstream of LAT.

PMID- 18826393
TI  - Reduction of the immune response to factor VIII mediated through tolerogenic
      factor VIII presentation by immature dendritic cells.
AB  - BACKGROUND: The development of neutralizing antibodies to factor FVIII (FVIII)
      represents the most serious complication in the treatment of hemophilia A.
      OBJECTIVE: We have explored the potential of using immature dendritic cells
      (iDCs) to present FVIII in a tolerogenic manner to T cells. METHODS: The iDCs
      were isolated from hemophilic murine bone marrow and pulsed with canine cFVIII
      (cFVIII-iDCs) in the presence or absence of the NFkappaB pathway blocking
      compound Andrographolide (Andro-cFVIII-iDCs). Three weekly intravenous infusions
      of one million cFVIII pulsed-iDCs were administered to a group of five hemophilic
      Balb/c mice. Anti-FVIII antibody levels were monitored by functional Bethesda
      assay after four weekly intravenous challenges with 2 IU of cFVIII. RESULTS: We
      have shown that cFVIII in the presence or absence of Andro is efficiently taken
      up by iDCs and that this process does not result in the maturation of DCs or the
      activation of co-cultured T cells. Following repeated infusion of the cFVIII-iDCs
      and Andro-cFVIII-iDCs into hemophilic mice, which were subsequently challenged
      with cFVIII, long-term reductions of FVIII inhibitors of 25% and 40%,
      respectively, were documented. Studies of cytokine release and T-cell phenotypes
      indicate that the mechanisms responsible for reducing immunologic responsiveness
      to cFVIII appear to involve an expansion of Foxp3 T regulatory cells in the case
      of cFVIII-iDC infusion and the elaboration of the immunosuppressive cytokines IL
      10 and TGF-beta following andrographolide-treated cFVIII-iDCs. CONCLUSIONS: This
      study shows that tolerogenic presentation of cFVIII to the immune system can
      significantly reduce immunogenicity of the protein.

PMID- 18826394
TI  - Lack of association between variants in the VKORC1 gene and cerebrovascular or
      coronary heart disease.

PMID- 18826395
TI  - Blending web-based technology and live conference: continuing the discussion.

PMID- 18826396
TI  - Enriching the clerkship curriculum with blended e-learning.

PMID- 18826397
TI  - Assessing students' socio-cultural knowledge frameworks through concept.

PMID- 18826399
TI  - Applying health care informatics to improve  student learning.

PMID- 18826400
TI  - Using an online neurological localisation game.

PMID- 18826401
TI  - Attitudes towards the doctor-patient relationship: a prospective study in an
      Asian medical school.
AB  - CONTEXT: Patient-centredness is an accepted guiding principle for health system
      reform, patient care and medical education. Although these attitudes are strongly
      linked with cultural values, few studies have examined attitudes towards patient
      centredness in a cross-cultural setting. OBJECTIVES: This prospective study
      evaluated attitudes towards patient-centredness in a cohort of Asian medical
      students and examined changes in these attitudes in the same students on
      completion of their junior clinical clerkships. METHODS: The study was conducted
      in a cohort of 228 medical students entering Year 3 in medical school. The
      Patient-Practitioner Orientation Scale (PPOS), a validated instrument which
      scores an individual's level of patient-centredness, was used. RESULTS: Being
      female and having personal experience of continuing care were significantly
      associated with higher scores. Students in the USA were previously reported to
      have similar 'caring' but higher 'sharing' scores on the same scale. At the end
      of the junior clinical clerkship, there were improvements in the 'caring'
      subscale, but no change or a reduction in 'sharing'. Students who did not have
      previous personal experience with continuing care experienced a greater increase
      in overall PPOS score. CONCLUSIONS: When compared with students in the USA, the
      students in our study appear to have a lower propensity to view the doctor
      patient relationship as a partnership. This may be a reflection of differences in
      cultural norms and expectations of doctor-patient interaction in different
      societies. Our finding that attitudes towards patient-centredness did not decline
      over the course of the year, which contrasts with findings of other studies, may
      be attributed to various factors and warrants further study.

PMID- 18826402
TI  - Pilot test of a problem-based learning preceptor certification examination.

PMID- 18826404
TI  - Engagement and listening skills: identifying learning needs.

PMID- 18826403
TI  - The medical literature curriculum.

PMID- 18826405
TI  - From website to bedside: narrative-based e-learning.

PMID- 18826406
TI  - A shifty stop for a hairy tail.
AB  - The tail apparatus of the bacteriophage SPP1 is an extraordinary approximately
      1600-A-long molecular machine. The tail mediates attachment of the virus to the
      host surface receptor, as well-as ejection of the viral genome into the host. The
      distal tip of the tail binds the extracellular ectodomain of the Bacillus
      subtilis receptor YueB, while the tail tube provides a conduit to funnel the
      viral genome into the host. This process, which culminates with the ejection of
      the approximately 44 kb of viral DNA across the thick, cell envelope of the Gram
      positive bacterial cell, takes place in a time scale of seconds to minutes and
      represents a remarkable example of biotransformation. In this issue of Molecular
      Microbiology, Auzat et al. provide compelling evidence that the two major
      structural proteins of the SPP1 tail, gp17.1 (approximately 19.1 kDa) and gp17.1*
      (approximately 28 kDa), share a common N-terminal sequence, and that gp17.1* is
      generated by a translational frameshift in the gene 17.1. The extra domain fused
      to gp17.1* is synthesized by a +1 programmed translational frameshift at the end
      of gene 17.1, which leads to the synthesis of approximately one gp17.1* for every
      three equivalents of gp17.1. This finding extends our current knowledge of
      translational frameshifts and provides a framework to understand how Siphoviridae
      phages like SPP1 have developed long-tail machines using only two major
      structural proteins.

PMID- 18826407
TI  - Intrinsic properties of the two replicative DNA polymerases of Pyrococcus abyssi
      in replicating abasic sites: possible role in DNA damage tolerance?
AB  - Spontaneous and induced abasic sites in hyperthermophiles DNA have long been
      suspected to occur at high frequency. Here, Pyrococcus abyssi was used as an
      attractive model to analyse the impact of such lesions onto the maintenance of
      genome integrity. We demonstrated that endogenous AP sites persist at a slightly
      higher level in P. abyssi genome compared with Escherichia coli. Then, the two
      replicative DNA polymerases, PabpolB and PabpolD, were characterized in presence
      of DNA containing abasic sites. Both Pabpols had abortive DNA synthesis upon
      encountering AP sites. Under running start conditions, PabpolB could incorporate
      in front of the damage and even replicate to the full-length oligonucleotides
      containing a specific AP site, but only when present at a molar excess.
      Conversely, bypassing activity of PabpolD was strictly inhibited. The tight
      regulation of nucleotide incorporation opposite the AP site was assigned to the
      efficiency of the proof-reading function, because exonuclease-deficient enzymes
      exhibited effective TLS. Steady-state kinetics reinforced that Pabpols are high
      fidelity DNA polymerases onto undamaged DNA. Moreover, Pabpols preferentially
      inserted dAMP opposite an AP site, albeit inefficiently. While the template
      sequence of the oligonucleotides did not influence the nucleotide insertion, the
      DNA topology could impact on the progression of Pabpols. Our results are
      interpreted in terms of DNA damage tolerance.

PMID- 18826408
TI  - F plasmid partition depends on interaction of SopA with non-specific DNA.
AB  - Bacterial ATPases belonging to the ParA family assure partition of their
      replicons by forming dynamic assemblies which move replicon copies into the new
      cell-halves. The mechanism underlying partition is not understood for the Walker
      box ATPase class, which includes most plasmid and all chromosomal ParAs. The
      ATPases studied both polymerize and interact with non-specific DNA in an ATP
      dependent manner. Previous work showed that in vitro, polymerization of one such
      ATPase, SopA of plasmid F, is inhibited by DNA, suggesting that interaction of
      SopA with the host nucleoid could regulate partition. In an attempt to identify
      amino acids in SopA that are needed for interaction with non-specific DNA, we
      have found that mutation of codon 340 (lysine to alanine) reduces ATP-dependent
      DNA binding > 100-fold and correspondingly diminishes SopA activities that depend
      on it: inhibition of polymer formation and persistence, stimulation of basal
      level ATP hydrolysis and localization over the nucleoid. The K340A mutant
      retained all other SopA properties tested except plasmid stabilization;
      substitution of the mutant SopA for wild-type nearly abolished mini-F partition.
      The behaviour of this mutant indicates a causal link between interaction with the
      cell's non-specific DNA and promotion of the dynamic behaviour that ensures F
      plasmid partition.

PMID- 18826410
TI  - 'Form variation' of the O12 antigen is critical for persistence of Salmonella
      Typhimurium in the murine intestine.
AB  - Salmonella enterica subspecies I serotypes are responsible for the vast majority
      of salmonellosis in mammals and birds, yet only a few factors specific to this
      group that allow them to persist in this niche have been identified. We show that
      STM0557, a S. enterica subspecies I-specific gene encoding an inner membrane
      protein, is critical for faecal shedding and intestinal persistence of S.
      enterica serotype Typhimurium ATCC14028 in Salmonella-resistant mice, but
      mutations in this gene do not diminish short-term intestinal colonization or
      invasion of cultured epithelial cells. STM0557 and two neighbouring genes,
      located on a pathogenicity island termed SPI-16, resemble genes of the gtrA,B,
      gtr(type) cluster in seroconverting bacteriophages. In general, the gtr genes
      encode proteins responsible for serotype conversion of the infected bacterium by
      addition glucose residues to repeating O-antigen subunits of lipopolysaccharide
      (LPS). In lysogenized Shigella, such modifications have been previously shown to
      be constitutively expressed and to facilitate invasion of host cells. We show
      that serotype Typhimurium gtr orthologues, STM0557-0559, are responsible for
      'form variation' or glucosylation of the O12 antigen galactose (4 position) to
      generate the 12-2 variant. Form variation in Typhimurium is not constitutive, but
      occurred upon exposure and during intracellular growth of serotype Typhimurium in
      J774 macrophages. Our data suggest that the 12-2 antigen is a S. enterica
      subspecies I-specific LPS modification that enhances long-term intestinal
      colonization, and is in contrast to the role of O-antigen variation described for
      Shigella.

PMID- 18826409
TI  - Rsd family proteins make simultaneous interactions with regions 2 and 4 of the
      primary sigma factor.
AB  - Bacterial anti-sigma factors typically regulate sigma factor function by
      restricting the access of their cognate sigma factors to the RNA polymerase
      (RNAP) core enzyme. The Escherichia coli Rsd protein forms a complex with the
      primary sigma factor, sigma(70), inhibits sigma(70)-dependent transcription in
      vitro, and has been proposed to function as a sigma(70)-specific anti-sigma
      factor, thereby facilitating the utilization of alternative sigma factors. In
      prior work, Rsd has been shown to interact with conserved region 4 of sigma(70),
      but it is not known whether this interaction suffices to account for the
      regulatory functions of Rsd. Here we show that Rsd and the Rsd orthologue AlgQ, a
      global regulator of gene expression in Pseudomonas aeruginosa, interact with
      conserved region 2 of sigma(70). We show further that Rsd and AlgQ can interact
      simultaneously with regions 2 and 4 of sigma(70). Our findings establish that the
      abilities of Rsd and AlgQ to interact with sigma(70) region 2 are important
      determinants of their in vitro and in vivo activities.

PMID- 18826411
TI  - Characterization of Bacillus anthracis iron-regulated surface determinant (Isd)
      proteins containing NEAT domains.
AB  - Three iron-regulated surface determinant (Isd) proteins, containing NEAr
      Transporter (NEAT) domains (GBAA4789-7), constitute part of an eight-member
      Bacillus anthracis operon. GBAA4789 (IsdC), previously characterized by others as
      a haem-binding protein, and two novel Isd proteins characterized in this study,
      GBAA4788 (IsdJ) and GBAA4787 (IsdK) proteins, can be translated from two
      alternative overlapping transcriptional units. The three NEAT-containing Isd
      proteins are shown to be expressed in vivo during B. anthracis infection.
      Expression in vitro is regulated by iron ions independent of the virulence
      plasmids pXO1 and pXO2, yet their presence affects the range of response to iron
      ion concentration. The expression of IsdC, J and K is strongly repressed under
      high CO(2) tension, conditions that are optimal for B. anthracis toxin and
      capsule expression, suggesting that these Isd proteins are elements of a B.
      anthracis'air-regulon'. Deletion mutants of isdC, isdK or the entire isdCJK locus
      are as virulent and pathogenic to guinea pigs as the fully virulent wild-type
      Vollum strain. The isdC-deleted mutant is defective in sequestration of haemin,
      consistent with previous biochemical observations, while the DeltaisdK mutant is
      defective in haemoglobin uptake. Studies with recombinant IsdK demonstrate
      specific binding to haemoglobin.

PMID- 18826412
TI  - A conserved domain of previously unknown function in Gap1 mediates protein
      protein interaction and is required for biogenesis of a serine-rich streptococcal
      adhesin.
AB  - Fap1-like serine-rich proteins are a new family of bacterial adhesins found in a
      variety of streptococci and staphylococci that have been implicated in bacterial
      pathogenesis. A gene cluster encoding glycosyltransferases and accessory Sec
      components is required for Fap1 glycosylation and biogenesis in Streptococcus
      parasanguinis. Here we report that the glycosylation-associated protein, Gap1,
      contributes to glycosylation and biogenesis of Fap1 by interacting with another
      glycosylation-associated protein, Gap3. Gap1 shares structural homology with
      glycosyltransferases. The gap1 mutant, like the gap3 mutant, produced an
      aberrantly glycosylated Fap1 precursor and failed to produce mature Fap1,
      suggesting that Gap1 and Gap3 might function in concert in the Fap1 glycosylation
      and biogenesis. Indeed, Gap1 interacted with Gap3 in vitro and in vivo. A Gap1 N
      terminal motif, within a highly conserved domain of unknown function (DUF1975)
      identified in many bacterial glycosyltransferases, was required for the Gap1-Gap3
      interaction. Deletion of one, four and nine amino acids within the conserved
      motif gradually inhibited the Gap1-Gap3 interaction and diminished production of
      mature Fap1 and concurrently increased production of the Fap1 precursor.
      Consequently, bacterial adhesion to an in vitro tooth model was also reduced.
      These data demonstrate that the Gap1-Gap3 interaction is required for Fap1
      biogenesis and Fap1-dependent bacterial adhesion.

PMID- 18826413
TI  - Uses and misuses of multicriteria decision analysis (MCDA) in environmental
      decision making.
AB  - We focus on a class of multicriteria methods that are commonly used in
      environmental decision making--those that employ the weighted linear average
      algorithm (and this includes the popular analytic hierarchy process (AHP)). While
      we do not doubt the potential benefits of using formal decision methods of this
      type, we draw attention to the consequences of not using them well. In
      particular, we highlight a property of these methods that should not be
      overlooked when they are applied in environmental and wider decision-making
      contexts: the final decision or ranking of options is dependent on the choice of
      performance scoring scales for the criteria when the criteria weights are held
      constant. We compare this "sensitivity" to a well-known criticism of the AHP, and
      we go on to describe the more general lesson when it comes to using weighted
      linear average methods--a lesson concerning the relationship between criteria
      weights and performance scoring scales.

PMID- 18826414
TI  - Are adult patients more tolerant of treatment risks than parents of juvenile
      patients?
AB  - Understanding patient-specific differences in risk tolerance for new treatments
      that offer improved efficacy can assist in making difficult regulatory and
      clinical decisions for new treatments that offer both the potential for greater
      effectiveness in relieving disease symptoms, but also risks of disabling or fatal
      side effects. The aim of this study is to elicit benefit-risk trade-off
      preferences for hypothetical treatments with varying efficacy and risk levels
      using a stated-choice (SC) survey. We derive estimates of "maximum acceptable
      risk" (MAR) that can help decisionmakers identify welfare-enhancing alternatives.
      In the case of children, parent caregivers are responsible for treatment
      decisions and their risk tolerance may be quite different than adult patients'
      own tolerance for treatment-related risks. We estimated and compared the
      willingness of Crohn's disease (CD) patients and parents of juvenile CD patients
      to accept serious adverse event (SAE) risks in exchange for symptom relief. The
      analyzed data were from 345 patients over the age of 18 and 150 parents of
      children under the age of 18. The estimation results provide strong evidence that
      adult patients and parents of juvenile patients are willing to accept tradeoffs
      between treatment efficacy and risks of SAEs. Parents of juvenile CD patients are
      about as risk tolerant for their children as adult CD patients are for themselves
      for improved treatment efficacy. SC surveys provide a systematic method for
      eliciting preferences for benefit-risk tradeoffs. Understanding patients' own
      risk perceptions and their willingness to accept risks in return for treatment
      benefits can help inform risk management decision making.

PMID- 18826415
TI  - Securing passenger aircraft from the threat of man-portable air defense systems
      (MANPADS).
AB  - In this article, we develop a model for the expected maximum hit probability of
      an attack on a commercial aircraft using MANPADS, as a function of the (random)
      location of the attacker. We also explore the sensitivity of the expected maximum
      hit probability to the parameters of the model, including both attacker
      parameters (such as weapon characteristics) and defender parameters (such as the
      size of the secure region around the airport). We conclude that having a large
      secure region around an airport offers some protection against MANPADS, and that
      installing onboard countermeasures reduces the success probability of a MANPADS
      attack.

PMID- 18826416
TI  - How a system backfires: dynamics of redundancy problems in security.
AB  - Increasing attention is being paid to reliability, safety, and security issues in
      social systems. Scott Sagan examined why more security forces (a redundancy
      solution) may lead to less security. He discussed how such a solution can
      backfire due to three major issues (i.e., "common-mode error,""social shirking,"
      and "overcompensation"). In this article, using Sagan's hypotheses, we simulate
      and analyze a simple and generic security system as more guards are added to the
      system. Simulation results support two of Sagan's hypotheses. More specifically,
      the results show that "common-mode error" causes the system to backfire, and
      "social shirking" leads to an inefficient system while exacerbating the common
      mode error's effect. Simulation results show that "overcompensation" has no
      effect of backfiring, but it leads the system to a critical state in which it can
      easily be affected by the common-mode error. Furthermore, the simulation results
      make us question the importance of the initial power of adversaries (e.g.,
      terrorists) as the results show that, for any exogenous level of adversary power,
      the system endogenously overcompensates to a level that makes the system more
      susceptible to being attacked.

PMID- 18826417
TI  - "Trust me, I'm a scientist (not a developer)": perceived expertise and motives as
      predictors of trust in assessment of risk from contaminated land.
AB  - Previous authors have argued that trust may be based on the extent to which risk
      communicators are seen as good at discriminating safety from danger, are unbiased
      in their assessments, and share their audience's values. Residents of two English
      urban regions rated their trust in six potential sources of information about the
      risk of contaminated land in their neighborhood (independent scientists; local
      council property developers; residents' groups; friends and family; local media),
      and how expert, open, accurate, or biased these sources were and how much they
      had residents' interests at heart. Overall, scientists were trusted most and
      developers least, but this was only partly due to their greater perceived
      expertise. Resident groups and friends/family were also trusted, despite being
      seen as relatively inexpert, since they scored highly on openness and shared
      interests, these latter two attributes being more important predictors of trust
      in individual sources than perceived expertise. We conclude that, where a source
      is seen as motivated to withhold, distort, or misinterpret information, this will
      undermine public trust even in apparently knowledgeable sources, hence supporting
      the view that trust depends on a combination of perceived expertise and perceived
      motives as complementary processes.

PMID- 18826418
TI  - Brain activation on pre-reading tasks reveals at-risk status for dyslexia in 6
      year-old children.
AB  - In this fMRI-study, 6-year-old children considered at risk for dyslexia were
      compared with an age-/gender-matched control group for differences in brain
      activation when presented with visual stimuli differing in demands for literacy
      processing. Stimuli were nameable pictures, brand logos familiar to children, and
      written words - these were either regularly spelled using early-acquired rules
      ("alphabetic") or more complex ("orthographic"). Brain responses distinguished
      between the presentation conditions, as a function of group, within many cortical
      areas. Activation in the alphabetic and orthographic conditions in the left
      angular gyrus correlated with individual at-risk index scores, and activation in
      inferior occipito-temporal regions further indicated differential activation for
      the two groups related to orthographic processing, especially. Since similar
      patterns are reported in adult dyslexics when processing written words, it
      appears that sensitivity to the cortical differentiation of reading networks is
      established prior to formal literacy training.

PMID- 18826419
TI  - Psychometric examination and normative data for the narcissistic personality
      inventory 29 item version.
AB  - The Narcissistic Personality Inventory (NPI) is commonly used in empirical
      studies of narcissism. Few population-based studies have been published. Our aim
      was to do a confirmatory factor analysis (CFA) of the NPI 29 item version with a
      four-factor structure, in two population-based samples and in a patient sample,
      and present normative population-based data. The NPI-29 was filled in by 324
      respondents from the Norwegian population, 231 from the Swedish population and
      167 Norwegian psychiatric patients. The four-factor structure of the NPI-29 with
      Leadership/Power, Exhibitionism/Self-admiration, Superiority/Arrogance and
      Uniqueness/Entitlement was reproduced in these samples. The CFA models showed
      good fit indices in all samples. Mean scores on the NPI-29 and four subscales
      hardly differed between the samples. For the NPI-29 total score and factors, few
      significant differences were observed. CFA of the samples supported the factor
      structure of the NPI-29 formerly identified by principal component analysis of
      the Swedish population sample.

PMID- 18826420
TI  - Internet addiction among Norwegian adults: a stratified probability sample study.
AB  - Most Norwegians are Internet users. We conducted a stratified probability sample
      study (Norway, 2007, age-group 16-74 years, N= 3,399, response rate 35.3%, 87.1%
      Internet users) to assess the prevalence of Internet addiction and at-risk
      Internet use by the Young Diagnostic Questionnaire (YDQ). The prevalence of
      Internet addiction (YDQ score 5-8) was 1.0% and an additional 5.2% were at-risk
      Internet users (YDQ score 3-4). Internet addiction and at-risk Internet use was
      strongly dependent on gender and age with highest prevalences among young males
      (16-29 years 4.1% and 19.0%, 30-39 years 3.3% and 10.7%). Logistic regression
      showed that male gender, young age, university level education, and an
      unsatisfactory financial situation were factors positively associated with
      "problematic Internet use" (at-risk and addicted use combined). Time spent on the
      Internet and prevalence of self-reported sleeping disorders, depression, and
      other psychological impairments increased linearly with YDQ score. Problematic
      Internet use clearly affects the lives of many people.

PMID- 18826421
TI  - The effects of cystic fibrosis on couples: marital satisfaction, emotions, and
      coping strategies.
AB  - An earlier diagnosis and better overall multidisciplinary care enable people
      suffering from Cystic Fibrosis (CF) to have a life expectancy of 40.
      Consequently, new populations and questions about the development of the life of
      couples have arisen. This study by questionnaires takes a first look at marital
      adjustment, anxiety, depression, and emotion focused, social support focused, and
      problem focused coping strategies in 16 CF patients and their partners. As a
      whole, the couples' marital adjustment level was good; it was higher for men who
      were patients than men who were partners, and vice versa for women. Anxiety was
      high for at least one partner in 10 of the couples; depression, for at least one
      partner in seven of them. The participants seem to use coping strategies to a
      lesser extent than the general population. The results are discussed in terms of
      how the quality of life as a couple with one partner suffering from CF is
      affected by the proper mutual adjustment of the partners.

PMID- 18826422
TI  - Central executive function in mild cognitive impairment: a PET activation study.
AB  - Using positron emission tomography (PET), we explored the neural correlates of an
      executive function, dual tasking, in patients with amnestic mild cognitive
      impairment (aMCI) and in elderly controls. The experiment employed simple
      auditory and visual tasks that were presented both in isolation and
      simultaneously to create a task condition requiring enhanced attentional control.
      Behaviorally, both groups performed well, albeit the patients made more errors on
      the visual task. The PET analysis focused at prefrontal regions where group
      differences in task-related activation patterns were expected. During dual task
      performance, the patients showed attenuated activity in the left inferior frontal
      region when compared to the controls. This suggests abnormalities in the neural
      processes underlying attentional control in aMCI.

PMID- 18826423
TI  - Visual attention capacity: a review of TVA-based patient studies.
AB  - Psychophysical studies have identified two distinct limitations of visual
      attention capacity: processing speed and apprehension span. Using a simple test,
      these cognitive factors can be analyzed by Bundesen's Theory of Visual Attention
      (TVA). The method has strong specificity and sensitivity, and measurements are
      highly reliable. As the method is theoretically founded, it also has high
      validity. TVA-based assessment has recently been used to investigate a broad
      range of neuropsychological and neurological conditions. We present the method,
      including the experimental paradigm and practical guidelines to patient testing,
      and review existing TVA-based patient studies organized by lesion anatomy.
      Lesions in three anatomical regions affect visual capacity: The parietal lobes,
      frontal cortex and basal ganglia, and extrastriate cortex. Visual capacity thus
      depends on large, bilaterally distributed anatomical networks that include
      several regions outside the visual system. The two visual capacity parameters are
      functionally separable, but seem to rely on largely overlapping brain areas.

PMID- 18826424
TI  - Cognitive and linguistic skills in Swedish children with cochlear implants -
      measures of accuracy and latency as indicators of development.
AB  - The purpose of the present study was to examine working memory (WM) capacity,
      lexical access and phonological skills in 19 children with cochlear implants (CI)
      (5;7-13;4 years of age) attending grades 0-2, 4, 5 and 6 and to compare their
      performance with 56 children with normal hearing. Their performance was also
      studied in relation to demographic factors. The findings indicate that children
      with CI had visuospatial WM capacities equivalent to the comparison group. They
      had lower performance levels on most of the other cognitive tests. Significant
      differences between the groups were not found in all grades and a number of
      children with CI performed within 1 SD of the mean of their respective grade
      matched comparison group on most of the cognitive measures. The differences
      between the groups were particularly prominent in tasks of phonological WM. The
      results are discussed with respect to the effects of cochlear implants on
      cognitive development.

PMID- 18826425
TI  - Emotionally controlled decision-making and a gene variant related to serotonin
      synthesis in women with borderline personality disorder.
AB  - The Iowa Gambling Task (IGT) was used to examine (i) social decision-making in
      women with borderline personality disorder (BPD), and (ii) the relationship
      between impaired decision-making and the tryptophan hydroxylase-1 (TPH-1) gene,
      involved in serotonin synthesis. Forty-two women with BPD and a history of
      suicide attempts were genotyped, and the frequency of a TPH-1 haplotype
      previously uniquely associated with BPD was calculated. The BPD group scored
      significantly lower than a control group in the IGT. Furthermore, the TPH-1
      haplotype displayed a significantly higher frequency in BPD participants with
      impaired decision making, compared to BPD participants with normal scores. These
      findings suggest that impaired decision-making as determined by the IGT is a
      feature of BPD and may be (i) associated with serotonin dysfunction, and (ii)
      possibly relevant for suicidal behavior.

PMID- 18826426
TI  - Expert judgment in cases of alleged child sexual abuse: clinicians' sensitivity
      to suggestive influences, pre-existing beliefs and base rate estimates.
AB  - Clinicians' expertise in child sexual abuse (CSA) cases was explored by giving a
      questionnaire covering clinical experience, self-evaluated expertise, beliefs and
      attitudes about CSA and a trial material concerning CSA to 320 child mental
      health professionals. In the material the suggestiveness of the interview with
      the child was varied and one condition did not contain any interview transcript.
      Participants were sensitive to the presence of leading questions but not to the
      presence of other suggestive techniques and not to the possibility that
      suggestive techniques could have been used when no interview transcripts were
      included. Experience only affected sensitivity to leading questions. Strong
      attitudes and beliefs lessened the sensitivity to leading questions and made
      participants more prone to wanting the case to be prosecuted when other
      suggestive influences than leading questions were present. Practical implications
      of the results will be discussed.

PMID- 18826427
TI  - Ferritins control interaction between iron homeostasis and oxidative stress in
      Arabidopsis.
AB  - Ferritin protein nanocages are the main iron store in mammals. They have been
      predicted to fulfil the same function in plants but direct evidence was lacking.
      To address this, a loss-of-function approach was developed in Arabidopsis. We
      present evidence that ferritins do not constitute the major iron pool either in
      seeds for seedling development or in leaves for proper functioning of the
      photosynthetic apparatus. Loss of ferritins in vegetative and reproductive organs
      resulted in sensitivity to excess iron, as shown by reduced growth and strong
      defects in flower development. Furthermore, the absence of ferritin led to a
      strong deregulation of expression of several metal transporters genes in the
      stalk, over-accumulation of iron in reproductive organs, and a decrease in
      fertility. Finally, we show that, in the absence of ferritin, plants have higher
      levels of reactive oxygen species, and increased activity of enzymes involved in
      their detoxification. Seed germination also showed higher sensitivity to pro
      oxidant treatments. Arabidopsis ferritins are therefore essential to protect
      cells against oxidative damage.

PMID- 18826428
TI  - Contribution of salicylic acid glucosyltransferase, OsSGT1, to chemically induced
      disease resistance in rice plants.
AB  - Systemic acquired resistance (SAR), a natural disease response in plants, can be
      induced chemically. Salicylic acid (SA) acts as a key endogenous signaling
      molecule that mediates SAR in dicotyledonous plants. However, the role of SA in
      monocotyledonous plants has yet to be elucidated. In this study, the mode of
      action of the agrochemical protectant chemical probenazole was assessed by
      microarray-based determination of gene expression. Cloning and characterization
      of the most highly activated probenazole-responsive gene revealed that it encodes
      UDP-glucose:SA glucosyltransferase (OsSGT1), which catalyzes the conversion of
      free SA into SA O-beta-glucoside (SAG). We found that SAG accumulated in rice
      leaf tissue following treatment with probenazole or 2,6-dichloroisonicotinic
      acid. A putative OsSGT1 gene from the rice cultivar Akitakomachi was cloned and
      the gene product expressed in Escherichia coli was characterized, and the results
      suggested that probenazole-responsive OsSGT1 is involved in the production of
      SAG. Furthermore, RNAi-mediated silencing of the OsSGT1 gene significantly
      reduced the probenazole-dependent development of resistance against blast
      disease, further supporting the suggestion that OsSGT1 is a key mediator of
      development of chemically induced disease resistance. The OsSGT1 gene may
      contribute to the SA signaling mechanism by inducing up-regulation of SAG in rice
      plants.

PMID- 18826429
TI  - Aluminum-activated citrate and malate transporters from the MATE and ALMT
      families function independently to confer Arabidopsis aluminum tolerance.
AB  - Aluminum-activated root malate and citrate exudation play an important role in
      plant Al tolerance. This paper characterizes AtMATE, a homolog of the recently
      discovered sorghum and barley Al-tolerance genes, shown here to encode an Al
      activated citrate transporter in Arabidopsis. Together with the previously
      characterized Al-activated malate transporter, AtALMT1, this discovery allowed us
      to examine the relationship in the same species between members of the two gene
      families for which Al-tolerance genes have been identified. AtMATE is expressed
      primarily in roots and is induced by Al. An AtMATE T-DNA knockdown line exhibited
      very low AtMATE expression and Al-activated root citrate exudation was abolished.
      The AtALMT1 AtMATE double mutant lacked both Al-activated root malate and citrate
      exudation and showed greater Al sensitivity than the AtALMT1 mutant. Therefore,
      although AtALMT1 is a major contributor to Arabidopsis Al tolerance, AtMATE also
      makes a significant but smaller contribution. The expression patterns of AtALMT1
      and AtMATE and the profiles of Al-activated root citrate and malate exudation are
      not affected by the presence or absence of the other gene. These results suggest
      that AtALMT1-mediated malate exudation and AtMATE-mediated citrate exudation
      evolved independently to confer Al tolerance in Arabidopsis. However, a link
      between regulation of expression of the two transporters in response to Al was
      identified through work on STOP1, a transcription factor that was previously
      shown to be necessary for AtALMT1 expression. Here we show that STOP1 is also
      required for AtMATE expression and Al-activated citrate exudation.

PMID- 18826430
TI  - The nodule inception-like protein 7 modulates nitrate sensing and metabolism in
      Arabidopsis.
AB  - Nitrate is an essential nutrient, and is involved in many adaptive responses of
      plants, such as localized proliferation of roots, flowering or stomatal
      movements. How such nitrate-specific mechanisms are regulated at the molecular
      level is poorly understood. Although the Arabidopsis ANR1 transcription factor
      appears to control stimulation of lateral root elongation in response to nitrate,
      no regulators of nitrate assimilation have so far been identified in higher
      plants. Legume-specific symbiotic nitrogen fixation is under the control of the
      putative transcription factor, NIN, in Lotus japonicus. Recently, the algal
      homologue NIT2 was found to regulate nitrate assimilation. Here we report that
      Arabidopsis thaliana NIN-like protein 7 (NLP7) knockout mutants constitutively
      show several features of nitrogen-starved plants, and that they are tolerant to
      drought stress. We show that nlp7 mutants are impaired in transduction of the
      nitrate signal, and that the NLP7 expression pattern is consistent with a
      function of NLP7 in the sensing of nitrogen. Translational fusions with GFP
      showed a nuclear localization for the NLP7 putative transcription factor. We
      propose NLP7 as an important element of the nitrate signal transduction pathway
      and as a new regulatory protein specific for nitrogen assimilation in non
      nodulating plants.

PMID- 18826431
TI  - TaASY1 promotes homologous chromosome interactions and is affected by deletion of
      Ph1.
AB  - During meiosis, chromosomes are sorted into homologous pairs as a preface to
      their intimate association via recombination and synapsis. However, little is
      known about the mechanism used to distinguish homologous chromosomes from other
      chromosomes present in the nucleus. Studies in wheat (Triticum aestivum) have
      shown that the Pairing homoeologous 1 (Ph1) locus is required to suppress
      interactions between genetically similar homoeologous chromosomes. Here we show
      that absence of Ph1 causes increased transcription of Asynapsis 1 (ASY1), a gene
      that encodes an axial-element-associated protein that is essential for synapsis
      and cross-over formation in Arabidopsis and rice. Localisation of ASY1 during
      meiosis is also affected by deletion of Ph1. In addition, transgenic wheat
      mutants with decreased activity of TaASY1 display reduced synapsis during
      prophase I and exhibit pairing between homoeologous chromosomes at metaphase I.
      These results suggest that ASY1 is required to promote interactions between
      homologous chromosomes in bread wheat, and that Ph1 has a gene regulatory role,
      which is consistent with its suggested genetic identity as a Cdk-like gene.
      Broader implications of this research suggest that we could use the Taasy1
      mutants to assess their efficacy in alien chromatin introgression studies, as
      seen with the ph1b mutant.

PMID- 18826432
TI  - The GhACS1 gene encodes an acyl-CoA synthetase which is essential for normal
      microsporogenesis in early anther development of cotton.
AB  - Microsporogenesis, associated with the functional expression of many genes, is a
      highly programmed and regulated process in flowering plants. To elucidate the
      roles of genes during anther development, two anther-specific cDNAs (designated
      GhACS1 and GhACS2) encoding acyl-CoA synthetases (ACSs) were isolated from a
      cotton (Gossypium hirsutum) flower cDNA library. Subsequently, the corresponding
      GhACS1 gene was isolated from a cotton genomic DNA library. Real-time
      quantitative RT-PCR and northern blot analyses revealed that GhACS1 transcripts
      were predominantly accumulated in the developing anthers of cotton. The
      specificity of GhACS1 expression in primary sporogenous cells (PSCs), pollen
      mother cells (PMCs), microspores, and tapetal cells was demonstrated by in situ
      hybridization as well as histochemical assay of GUS expression controlled under
      the GhACS1 promoter. High levels of GhACS1 activity are crucial for fatty acid
      metabolism in PSCs, PMCs, microspores and particularly tapetal cells. Reduction
      of ACS enzymatic activity by suppressing GhACS1 expression severely affected the
      tapetal cells and consequently blocked normal microsporogenesis in early anther
      development. Aberrant and defective microspores were generated in the transgenic
      anthers. As a result, the transgenic plants failed to produce functional pollen
      grains and were male-sterile, suggesting that the GhACS1 gene is required for
      normal microsporogenesis in early anther development of cotton.

PMID- 18826433
TI  - Effective, homogeneous and transient interference with cytosine methylation in
      plant genomic DNA by zebularine.
AB  - Covalent modification by methylation of cytosine residues represents an important
      epigenetic hallmark. While sequence analysis after bisulphite conversion allows
      correlative analyses with single-base resolution, functional analysis by
      interference with DNA methylation is less precise, due to the complexity of
      methylation enzymes and their targets. A cytidine analogue, 5-azacytidine, is
      frequently used as an inhibitor of DNA methyltransferases, but its rapid
      degradation in aqueous solution is problematic for culture periods of longer than
      a few hours. Application of zebularine, a more stable cytidine analogue with a
      similar mode of action that is successfully used as a methylation inhibitor in
      Neurospora and mammalian tumour cell lines, can significantly reduce DNA
      methylation in plants in a dose-dependent and transient manner independent of
      sequence context. Demethylation is connected with transcriptional reactivation
      and partial decondensation of heterochromatin. Zebularine represents a promising
      new and versatile tool for investigating the role of DNA methylation in plants
      with regard to transcriptional control, maintenance and formation of (hetero-)
      chromatin.

PMID- 18826434
TI  - The alpha 3 subunit gene of the nicotinic acetylcholine receptor is a candidate
      gene for ethanol stimulation.
AB  - Alcohol and nicotine are coabused, and preclinical and clinical data suggest that
      common genes may influence responses to both drugs. A gene in a region of mouse
      chromosome 9 that includes a cluster of three nicotinic acetylcholine receptor
      (nAChR) subunit genes influences the locomotor stimulant response to ethanol. The
      current studies first used congenic mice to confirm the influential gene on
      chromosome 9. Congenic F(2) mice were then used to more finely map the location.
      Gene expression of the three subunit genes was quantified in strains of mice that
      differ in response to ethanol. Finally, the locomotor response to ethanol was
      examined in mice heterozygous for a null mutation of the alpha 3 nAChR subunit
      gene (Chrna3). Congenic data indicate that a gene on chromosome 9, within a 46 cM
      region that contains the cluster of nAChR subunit genes, accounts for 41% of the
      genetic variation in the stimulant response to ethanol. Greater expression of
      Chrna3 was found in whole brain and dissected brain regions relevant to locomotor
      behavior in mice that were less sensitive to ethanol-induced stimulation compared
      to mice that were robustly stimulated; the other two nAChR subunit genes in the
      gene cluster (alpha 5 and beta 4) were not differentially expressed. Locomotor
      stimulation was not expressed on the genetic background of Chrna3 heterozygous
      (+/-) and wild-type (+/+) mice; +/- mice were more sensitive than +/+ mice to the
      locomotor depressant effects of ethanol. Chrna3 is a candidate gene for the acute
      locomotor stimulant response to ethanol that deserves further examination.

PMID- 18826435
TI  - Dynamics of Campylobacter colonization of a natural host, Sturnus vulgaris
      (European starling).
AB  - Wild European Starlings (Sturnus vulgaris) shed Campylobacter at high rates,
      suggesting that they may be a source of human and farm animal infection. A survey
      of Campylobacter shedding of 957 wild starlings was undertaken by culture of
      faecal specimens and genetic analysis of the campylobacters isolated: shedding
      rates were 30.6% for Campylobacter jejuni, 0.6% for C. coli and 6.3% for C. lari.
      Genotyping by multilocus sequence typing (MLST) and antigen sequence typing
      established that these bacteria were distinct from poultry or human disease
      isolates with the ST-177 and ST-682 clonal complexes possibly representing
      starling-adapted genotypes. There was seasonal variation in both shedding rate
      and genotypic diversity, both exhibiting a maximum during the late spring/early
      summer. Host age also affected Campylobacter shedding, which was higher in
      younger birds, and turnover was rapid with no evidence of cross-immunity among
      Campylobacter species or genotypes. In nestlings, C. jejuni shedding was evident
      from 9 days of age but siblings were not readily co-infected. The dynamics of
      Campylobacter infection of starlings differed from that observed in commercial
      poultry and consequently there was no evidence that wild starlings represent a
      major source of Campylobacter infections of food animals or humans.

PMID- 18826436
TI  - Microbial eukaryotes in the hypersaline anoxic L'Atalante deep-sea basin.
AB  - The frontiers of eukaryote life in nature are still unidentified. In this study,
      we analysed protistan communities in the hypersaline (up to 365 g l(-1) NaCl)
      anoxic L'Atalante deep-sea basin located in the eastern Mediterranean Sea.
      Targeting 18S ribosomal RNA retrieved from the basin's lower halocline (3501 m
      depth) we detected 279 protistan sequences that grouped into 42 unique phylotypes
      (99% sequence similarity). Statistical analyses revealed that these phylotypes
      account only for a proportion of the protists inhabiting this harsh environment
      with as much as 50% missed by this survey. Most phylotypes were affiliated with
      ciliates (45%), dinoflagellates (21%), choanoflagelates (10%) and uncultured
      marine alveolates (6%). Sequences from other taxonomic groups like stramenopiles,
      Polycystinea, Acantharea and Euglenozoa, all of which are typically found in non
      hypersaline deep-sea systems, are either missing or very rare in our cDNA clone
      library. Although many DHAB sequences fell within previously identified
      environmental clades, a large number branched relatively deeply. Phylotype
      richness, community membership and community structure differ significantly from
      a deep seawater reference community (3499 m depth). Also, the protistan community
      in the L'Atalante basin is distinctively different from any previously described
      hypersaline community. In conclusion, we hypothesize that extreme environments
      may exert a high selection pressure possibly resulting in the evolution of an
      exceptional and distinctive assemblage of protists. The deep hypersaline anoxic
      basins in the Mediterranean Sea provide an ideal platform to test for this
      hypothesis and are promising targets for the discovery of undescribed protists
      with unknown physiological capabilities.

PMID- 18826437
TI  - Reverse dissimilatory sulfite reductase as phylogenetic marker for a subgroup of
      sulfur-oxidizing prokaryotes.
AB  - Sulfur-oxidizing prokaryotes (SOP) catalyse a central step in the global S-cycle
      and are of major functional importance for a variety of natural and engineered
      systems, but our knowledge on their actual diversity and environmental
      distribution patterns is still rather limited. In this study we developed a
      specific PCR assay for the detection of dsrAB that encode the reversely operating
      sirohaem dissimilatory sulfite reductase (rDSR) and are present in many but not
      all published genomes of SOP. The PCR assay was used to screen 42 strains of SOP
      (most without published genome sequence) representing the recognized diversity of
      this guild. For 13 of these strains dsrAB was detected and the respective PCR
      product was sequenced. Interestingly, most dsrAB-encoding SOP are capable of
      forming sulfur storage compounds. Phylogenetic analysis demonstrated largely
      congruent rDSR and 16S rRNA consensus tree topologies, indicating that lateral
      transfer events did not play an important role in the evolutionary history of
      known rDSR. Thus, this enzyme represents a suitable phylogenetic marker for
      diversity analyses of sulfur storage compound-exploiting SOP in the environment.
      The potential of this new functional gene approach was demonstrated by
      comparative sequence analyses of all dsrAB present in published metagenomes and
      by applying it for a SOP census in selected marine worms and an alkaline lake
      sediment.

PMID- 18826438
TI  - Proteomics-inferred genome typing (PIGT) demonstrates inter-population
      recombination as a strategy for environmental adaptation.
AB  - Analyses of ecological and evolutionary processes that shape microbial consortia
      are facilitated by comprehensive studies of ecosystems with low species richness.
      In the current study we evaluated the role of recombination in altering the
      fitness of chemoautotrophic bacteria in their natural environment. Proteomics
      inferred genome typing (PIGT) was used to genotype the dominant Leptospirillum
      group II populations in 27 biofilms sampled from six locations in the Richmond
      Mine acid mine drainage system (Iron Mountain, CA) over a 4-year period. We
      observed six distinct genotypes that are recombinants comprised of segments from
      two 'parental' genotypes. Community genomic analyses revealed additional low
      abundance recombinant variants. The dominance of some genotypes despite a larger
      available genome pool, and patterns of spatiotemporal distribution within the
      ecosystem, indicate selection for distinct recombinants. Genes involved in
      motility, signal transduction and transport were over-represented in the tens to
      hundreds of kilobase recombinant blocks, whereas core metabolic functions were
      significantly under-represented. Our findings demonstrate the power of PIGT and
      reveal that recombination is a mechanism for fine-scale adaptation in this
      system.

PMID- 18826439
TI  - Subsurface microbiology and biogeochemistry of a deep, cold-water carbonate mound
      from the Porcupine Seabight (IODP Expedition 307).
AB  - The Porcupine Seabight Challenger Mound is the first carbonate mound to be
      drilled (approximately 270 m) and analyzed in detail microbiologically and
      biogeochemically. Two mound sites and a non-mound Reference site were analyzed
      with a range of molecular techniques [catalyzed reporter deposition-fluorescence
      in situ hybridization (CARD-FISH), quantitative PCR (16S rRNA and functional
      genes, dsrA and mcrA), and 16S rRNA gene PCR-DGGE] to assess prokaryotic
      diversity, and this was compared with the distribution of total and culturable
      cell counts, radiotracer activity measurements and geochemistry. There was a
      significant and active prokaryotic community both within and beneath the
      carbonate mound. Although total cell numbers at certain depths were lower than
      the global average for other subseafloor sediments and prokaryotic activities
      were relatively low (iron and sulfate reduction, acetate oxidation,
      methanogenesis) they were significantly enhanced compared with the Reference
      site. In addition, there was some stimulation of prokaryotic activity in the
      deepest sediments (Miocene, > 10 Ma) including potential for anaerobic oxidation
      of methane activity below the mound base. Both Bacteria and Archaea were present,
      with neither dominant, and these were related to sequences commonly found in
      other subseafloor sediments. With an estimate of some 1600 mounds in the
      Porcupine Basin alone, carbonate mounds may represent a significant prokaryotic
      subseafloor habitat.

PMID- 18826440
TI  - Pathological laughing as a manifestation in a clinically isolated brainstem
      syndrome: a case report.
AB  - The prevalence of pathological laughing and crying in multiple sclerosis (MS) is
      10%. It has been speculated that the anatomical lesion responsible for the
      pathological laughing is located in the pontine base, prefrontal cortex, and
      cerebellum. We report an 18-year-old male patient presenting with pathological
      laughing and hypomania. In his neurological examination, he had a euphoric effect
      with ataxic walking and dysarthria speech. He had a bilateral conjugated gaze
      limitation, with a prominent bilateral horizontal nystagmus on left gaze,
      dysmetria, dysdiadokokinesia, and remarkable dysfunction in a heel-to-shin test
      on the left. The IgG index in cerebrospinal fluid was normal with an oligoclonal
      band was present. In cranial MRI, there was a lesion on central pons which was
      hypointense in T1 images with contrast enhancement and hyperintense in T2 and
      flair images. Also another lesion in right brachium pontis which did not contrast
      enhancement but was hyperintense on T2 and flair images was present. There was an
      elevation of myoinositol/creatine ratio and choline and a reduction of NAA in
      proton MR spectroscopy. MR spectroscopic evaluation of the patient demonstrated
      the demyelination process. There has been no report of patients in whom
      pathological laughter was the presenting symptom of clinically isolated brainstem
      syndrome.

PMID- 18826441
TI  - Unilateral versus bilateral middle cerebral artery detection of right-to-left
      shunt by power M-mode transcranial doppler.
AB  - BACKGROUND AND PURPOSE: Comparison was performed between unilateral and bilateral
      power M-mode transcranial Doppler to detect right-to-left circulatory shunt
      (RLS). METHODS: Recorded Doppler data from 87 patients with confirmed RLS
      referred for transcatheter closure of patent foramen ovale were reanalyzed for
      embolic tracks (ET) counted from left and right temporal bone windows during
      bubble study. Unilateral counts were obtained by multiplying each side by 2;
      bilateral counts were obtained by summing left and right ET. Both unilateral and
      bilateral ET were converted to a 6-point logarithmic grade. Sex and age group
      subanalyses were performed. RESULTS: At rest, significantly more ET were detected
      with bilateral versus unilateral detection (P= .01), but not following Valsalva
      (P= .13). Unilateral and bilateral detection were equally able to detect large
      RLS (grades IV or V) following Valsalva (P= 1.00). For the group aged > or =55
      years, the right-hand side yielded greater ET than the left-hand side (mean
      difference 9%+/- 37; 95% confidence interval -3 to 21%) at rest (P= .01), but not
      following Valsalva (mean difference 1%+/- 25; 95% confidence interval -7 to 9%,
      P= .10). CONCLUSIONS: Unilateral detection of ET by power M-mode transcranial
      Doppler is equivalent to bilateral detection to assess RLS.

PMID- 18826442
TI  - Diffuse leukoencephalopathy and brain edema: unusual presentations of CNS relapse
      of acute myeloid leukemia.
AB  - An isolated CNS relapse is rarely seen in acute myeloid leukemia. However, it has
      a potentially fatal clinical outcome. We herein present the case of a 39-year-old
      man, who presented to our emergency room with horizontal diplopic images,
      vertigo, bilateral deafness, and progressing somnolence. Cerebral imaging
      revealed cerebral and cerebellar edema and a diffuse leukoencephalopathy. With
      the one-year-old history of an initially successfully treated FAB-M0 acute
      myeloid leukemia (AML) in mind, a lumbar puncture was carried out that showed a
      vast number of myeloid blasts in the morphologic analysis of the cerebrospinal
      fluid. In conjunction with normal findings in the peripheral blood-count with
      differential and the bone marrow examination a diagnosis of an isolated CNS
      relapse of the AML was made. Cytarabine chemotherapy was initiated and the
      symptoms resolved rapidly. To our surprise, cerebral imaging in the course of the
      treatment not only showed a resolution of the brain edema but also of the
      leukoencephalopathy, pointing to a direct infiltration of brain parenchyma by
      leukemic blasts. The case highlights the relevance of the CNS as a pharmacologic
      "sanctuary" for tumor cells in patients that on prior treatments have not
      received intrathecal chemotherapy or chemotherapeutics that cross the blood-brain
      barrier.

PMID- 18826443
TI  - Safety of angioplasty and stenting without thrombolysis for the treatment of
      early ischemic stroke.
AB  - BACKGROUND: Strokes from large-vessel atherosclerotic occlusions or severe
      stenoses are often resistant to re-canalization with thrombolytic agents. As in
      acute coronary syndromes, angioplasty and stenting for stroke may be used to
      achieve timely reperfusion with possibly less risk for hemorrhagic complications.
      METHODS: From a prospectively collected database, we have retrospectively
      reviewed cases of patients presenting acutely with an ischemic stroke or
      subacutely with fluctuating ischemic deficits due to a large-vessel
      atherosclerotic stenosis and who were treated with angioplasty and stenting
      without thrombolytics. Endpoints were reperfusion based on the Thrombolysis in
      Myocardial Infarction (TIMI) score, procedural complications, parenchymal
      hematoma formation leading to neurologic decline, and 30-day clinical improvement
      based on the National Institutes of Health Stroke scale (NIHSS). RESULTS: Nine
      patients with a mean age of 70 +/- 9 years and mean NIHSS of 18.3 +/- 5.0 were
      treated. Culprit stenotic lesions were located in the extracranial internal
      carotid artery (ICA) origin (2), intracranial ICA (2), tandem stenosis in the
      extra- and intracranial ICA (3), and middle cerebral artery (2). Eight patients
      were treated with angioplasty and adjunctive stenting; one of these patients also
      required snaring of thrombus from the middle cerebral artery. One patient was
      treated with angioplasty of an intracranial ICA stenosis alone. TIMI 3
      reperfusion was achieved in 8 (88.9%) patients. The mean 30-day improvement in
      the NIHSS was 15.5 +/- 5.6. Six patients had a NIHSS of 0 or 1 at 30 days. One
      patient died due to reasons unrelated to stroke or interventional procedure.
      There were no significant complications or parenchymal hemorrhages. CONCLUSIONS:
      In appropriately selected patients with ischemic deficits due to large artery
      atherosclerotic stenoses, angioplasty with adjunctive stenting can be safely
      performed. Such interventions may improve outcome without the use of
      thrombolysis.

PMID- 18826444
TI  - Serotonergic genes and amygdala activity in response to negative affective facial
      stimuli in Korean women.
AB  - Serotonergic genes have been implicated in mood disorders, alcoholism and certain
      personality traits. We investigated the possible relationship between several
      polymorphisms in the serotonin (5-HT) system and amygdala responses to negative
      facial stimuli in Korean women using functional magnetic resonance imaging. All
      participants were genotyped with regard to the following polymorphisms: the
      serotonin transporter-gene-linked polymorphic region (5-HTTLPR), tryptophan
      hydroxylase 2 (TPH2) G(-703)T, 5-HT(1A) C(-1019)G and 5-HT(2A) single nucleotide
      polymorphism (SNP) rs6311. We found increased activations in response to angry
      facial stimuli in the bilateral amygdala of subjects with the long allele of 5
      HTTLPR compared with those with two copies of the short allele. Higher
      activations in response to sad facial stimuli were found in the bilateral
      amygdala of subjects with the T/T genotype of 5-HT(2A) SNP rs6311, compared with
      C allele carriers, and in subjects with the G/G genotype of TPH2 G(-703)T,
      compared with those with T/T and G/T genotypes. Our results for individuals from
      an Asian population countered a previous finding for a Caucasian population and
      identified the moderating role of genetic background in the relationships between
      these serotonergic gene polymorphisms and amygdala function elicited by negative
      emotional stimuli.

PMID- 18826446
TI  - Personality endophenotypes for bipolar affective disorder: a family-based genetic
      association analysis.
AB  - Genetic analyses of complex conditions such as bipolar disorder (BD) may be
      facilitated by the use of intermediate phenotypes. Various personality traits are
      overrepresented in people with BD and their unaffected relatives, and may
      constitute genetically transmitted risk factors or endophenotypes of the illness.
      In this study, we administered a battery of seven different personality
      questionnaires comprising 19 subscales to 31 Caucasian BD families (n = 241). Ten
      of these personality traits showed significant evidence of heritability and were
      therefore selected as candidate endophenotypes. In addition, a principal
      components analysis produced two heritable components (negative affect and
      appetitive drive), which accounted for a considerable proportion of the variance
      (29% + 12%) and were also used in the analysis. A family-based quantitative
      association study was carried out using the orthogonal model from the
      quantitative transmission disequilibrium tests (QTDT) program. Monte Carlo
      permutations (M = 500), which allow for non-normal data and provide a global P
      value, corrected for multiple testing, were used to calculate empirical P values
      for the within-family component of association. The 3' untranslated region repeat
      polymorphism of the dopamine transporter gene (SLC6A3) was associated with self
      directedness (P < 0.0001) and negative affect (P = 0.010). The short allele of
      the serotonin transporter gene (SLC6A4) promoter polymorphism showed a trend
      toward association with higher harm avoidance (P = 0.016) and negative affect (P
      = 0.028). The catechol-o-methyltransferase val158met polymorphism was weakly
      associated with the personality traits, 'Spirituality' (P = 0.040) and irritable
      temperament (P = 0.022). Furthermore, the met allele of the brain-derived
      neurotrophic factor val66met polymorphism was associated with higher hyperthymic
      temperament scores. We raise the possibility that the 10R allele of the SLC6A3
      repeat polymorphism and the short allele of the SLC6A4 promoter variant
      constitute risk factors for irritable-aggressive and anxious-dysthymic subtypes
      of BD, respectively.

PMID- 18826447
TI  - Directional evolution of stockiness coevolves with ecology and locomotion in
      lizards.
AB  - Although studied in many taxa, directional macroevolution remains difficult to
      detect and quantify. We present an approach for detecting directional evolution
      in subclades of species when relatively few species are sampled, and apply it to
      studying the evolution of stockiness in Phrynosomatine lizards. Our approach is
      more sensitive to detecting the tempo of directional evolution than other
      available approaches. We use ancestral reconstruction and phylogenetic mapping of
      morphology to characterize the direction and magnitude of trait evolution. We
      demonstrate a directional trend toward stockiness in horned lizards, but not
      their sister groups, finding that stockier species tend to have relatively short
      and wide bodies, and relatively short heads, tails, and limbs. Ornstein-Uhlenbeck
      models show that the directional trend in horned lizards is due to a shift in
      selective regime and stabilizing selection as opposed to directional selection.
      Bayesian evolutionary correlation analyses indicate that stockier species run
      more slowly and eat a larger proportion of ants. Furthermore, species with larger
      horns tend to be slower and more ant-specialized. Directional evolution toward a
      stocky body shape has evolved in conjunction with changes in a suite of traits,
      representing a complex example of directional macroevolution.

PMID- 18826448
TI  - Modes of acquisition of Wolbachia: horizontal transfer, hybrid introgression, and
      codivergence in the Nasonia species complex.
AB  - Wolbachia are maternally inherited bacteria that infect a large number of insects
      and are responsible for different reproductive alterations of their hosts. One of
      the key features of Wolbachia biology is its ability to move within and between
      host species, which contributes to the impressive diversity and range of infected
      hosts. Using multiple Wolbachia genes, including five developed for Multi-Locus
      Sequence Typing (MLST), the diversity and modes of movement of Wolbachia within
      the wasp genus Nasonia were investigated. Eleven different Wolbachia were found
      in the four species of Nasonia, including five newly identified infections. Five
      infections were acquired by horizontal transmission from other insect taxa, three
      have been acquired by hybridization between two Nasonia species, which resulted
      in a mitochondrial-Wolbachia sweep from one species to the other, and at least
      three have codiverged during speciation of their hosts. The results show that a
      variety of transfer mechanisms of Wolbachia are possible even within a single
      host genus. Codivergence of Wolbachia and their hosts is uncommon and provides a
      rare opportunity to investigate long-term Wolbachia evolution within a host
      lineage. Using synonymous divergence among codiverging infections and host
      nuclear genes, we estimate Wolbachia mutation rates to be approximately one-third
      that of the nuclear genome.

PMID- 18826449
TI  - Postcopulatory female choice increases the fertilization success of novel males
      in the field cricket, Gryllus vocalis.
AB  - Although recent studies have demonstrated that female crickets prefer novel males
      to previous mates, the relative contribution of pre- and postcopulatory behaviors
      to this advantage remain unknown, as do the reproductive consequences to males. I
      paired females either with previous or novel mates, and recorded the latency to
      mating and the time after mating at which the female removed the male's
      spermatophore, terminating sperm transfer. Females that mated with familiar males
      removed their spermatophores sooner than females that mated with novel males.
      Females paired with novel males also mated more quickly than females paired with
      familiar males, but this difference was not statistically significant. A
      molecular-based paternity analysis was used to determine whether the
      postcopulatory preference of females for novel males influences a male's
      fertilization success. Females were assigned to either mate three times with the
      same male and then once with a novel male, or four times with four different
      males. The paternity of the last male was higher when the female previously had
      mated repeatedly with the same male than when she had mated previously with
      different males. These results suggest that female spermatophore removal behavior
      influences male paternity such that novel males receive a fertility benefit.

PMID- 18826450
TI  - Temporal patterns of diversification and microendemism in Eastern Highland
      endemic barcheek darters (Percidae: Etheostomatinae).
AB  - Eastern North America is the location of the world's most species-rich temperate
      freshwater fish fauna. Hypotheses regarding the geographic and temporal scale of
      teleost diversification in this region have not been broadly investigated using
      absolute divergence time estimates among the constituent lineages. This study
      used time-calibrated molecular phylogenies estimated from mitochondrial and
      nuclear genes to investigate the temporal and geographic signatures of
      diversification within barcheek darters, a clade of allopatrically distributed
      species endemic to the Eastern Highlands. Results from divergence time estimates
      using an uncorrelated lognormal model suggest that the barcheek darters are an
      ancient group with a crown node estimate of 16.3 mya, 95% highest posterior
      density (HPD): [12.4, 20.5], and the clade is characterized by substantial
      intraspecific divergence times within several species. In particular, the Caney
      Fork endemic Etheostoma basilare comprises five strongly supported and deeply
      divergent clades with a most recent common ancestor estimated at 8.0 mya, 95%
      HPD: [5.6, 10.7]. These results are concordant with the hypothesis that
      geologically stable areas of eastern North America have facilitated both the
      generation and preservation of lineages across a substantial breadth of
      evolutionary time, and that allopatric speciation in darters has occurred at much
      smaller spatial scales than previously realized.

PMID- 18826451
TI  - Update on the role of vitamin K in skeletal health.
AB  - A protective role for vitamin K in bone health has been suggested based on its
      role as an enzymatic cofactor. In observational studies, vitamin K insufficiency
      is generally associated with lower bone mass and increased hip fracture risk.
      However, these findings are not supported in randomized controlled trials (RCT)
      of phylloquinone (vitamin K(1)) supplementation and bone loss at the hip in the
      elderly. This suggests that increased vegetable and legume intakes may
      simultaneously improve measures of vitamin K status and skeletal health, even
      though the mechanisms underlying these improvements may be independent of each
      other. Menaquinone-4 (vitamin K(2)), when given at pharmacological doses, appears
      to protect against fracture risk and bone loss at the spine. However, there are
      emerging data that suggest the efficacy of vitamin K supplementation on bone loss
      is inconclusive.

PMID- 18826452
TI  - Nutritional and dietary influences on attention deficit hyperactivity disorder.
AB  - An abundance of research has investigated causes and treatments for attention
      deficit hyperactivity disorder (ADHD). The research includes identification of
      suboptimal levels of nutrients and sensitivities to certain foods and food
      additives. This review gives an overview of this research and provides an up-to
      date account of clinical trials that have been conducted with zinc, iron,
      magnesium, Pycnogenol, omega-3 fatty acids, and food sensitivities. A literature
      search was conducted using PubMed, ISI Web of Knowledge, and Google Scholar and
      included studies published before April 2008. Although further research is
      required, the current evidence supports indications of nutritional and dietary
      influences on behavior and learning in these children, with the strongest support
      to date reported for omega-3s and behavioral food reactions.

PMID- 18826453
TI  - Should glycemic index and glycemic load be considered in dietary recommendations?
AB  - High glycemic index (GI) and glycemic load (GL) have been proposed to be
      associated with increased risk of lifestyle diseases. Since protein intake varies
      little in humans, adherence to the common recommendation to reduce fat intake
      probably leads to increases in carbohydrate intake, which emphasizes the need to
      investigate the effects of carbohydrate on diet-related conditions and diseases.
      This review examines the epidemiological literature linking GI and GL to heart
      disease, insulin sensitivity, type 2 diabetes, dyslipidemia, and obesity among
      initially healthy people. The evidence for associations between GI and
      particularly GL and health among free-living populations is mixed. Only the
      positive association between GI and development of type 2 diabetes was consistent
      across cross-sectional and longitudinal studies for both sexes. Low GI/GL may
      protect against heart disease in women, and cross-sectional studies indicate low
      GI/GL may reduce high-density-lipoprotein cholesterol and triacylglycerol levels
      in both sexes. Based on the evidence found in this review, it seems premature to
      include GI/GL in dietary recommendations.

PMID- 18826454
TI  - Resveratrol and novel potent activators of SIRT1: effects on aging and age
      related diseases.
AB  - Studies show that the plant polyphenol resveratrol can extend the life span of
      yeast, worms, flies, and fish. It also mitigates the metabolic dysfunction of
      mice fed high-fat diets. Resveratrol appears to mediate these effects partly by
      activating SIRT1, a deacetylase enzyme that regulates the activity of several
      transcriptional factors and enzymes responsive to nutrient availability. However,
      few foods contain resveratrol and humans metabolize it extensively, resulting in
      very low systemic bioavailability. Substantial research effort now focuses on
      identifying and testing more bioavailable and potent activators of SIRT1 for use
      as pharmacologic interventions in aging and age-related disorders.

PMID- 18826455
TI  - Role of fatty acids in the development of insulin resistance and type 2 diabetes
      mellitus.
AB  - Insulin resistance is defined as the reduced responsiveness to normal circulating
      levels of insulin. It is the basic condition of type 2 diabetes mellitus, in
      which both experimental animals and humans accumulate lipids intracellularly in
      skeletal muscle and liver. Measurement of these lipids in humans, using nuclear
      magnetic resonance spectroscopy after lipid infusion, indicated they could cause
      inhibition of the glucose transporter GLUT4, thereby suppressing glucose entry
      into cells and inhibiting glucose oxidation and glycogen synthesis in muscle.
      Furthermore, it is known that the enzyme acetyl-CoA carboxylase2 (ACC2)
      suppresses the oxidation of fatty acids by inhibiting the entry of fatty acids
      into mitochondria. Further support for the lipocentric hypothesis of the
      pathogenesis of insulin resistance was provided by knocking out the gene coding
      for ACC2 in mice; this led to greater fatty acid oxidation, reduced fat mass and,
      in consequence, greatly enhanced insulin sensitivity. These studies suggest that
      a specific inhibitor of ACC2 would have therapeutic potential for type 2 diabetes
      mellitus.

PMID- 18826456
TI  - Can the controversial relationship between dietary calcium and body weight be
      mechanistically explained by alterations in appetite and food intake?
AB  - The prevalence of obesity has reached epidemic proportions worldwide and the
      incidence of overweight and obesity continues to rise. Diet plays a significant
      role in the modulation of body weight and there is some evidence to suggest that
      calcium or dairy intake may modulate body weight and body fat mass. Several
      mechanisms through which calcium or dairy products may affect body weight or fat
      have been suggested, including a possible effect on appetite and food intake. A
      recent study investigated to what extent people could compensate for increased
      energy intake from dairy products and found that a 7-day increase in dairy intake
      had no effect on appetite and no evidence of complete compensation for the raised
      energy intake. In another study, the effects of altered calcium content of a
      dairy-based test meal was evaluated in obese subjects; the findings indicated
      that although a higher calcium content of the meal reduced the extent of post
      prandial chylomicron-associated triglyceridemia, there was no effect on appetite
      related hormones (CCK, ghrelin, GLP-1, or PPY) or on energy intake from a
      subsequent ad libitum test meal. Thus, this new evidence does not support the
      hypothesis that high calcium or dairy intake reduces appetite or food intake.

PMID- 18826460
TI  - Workplace stressors and coping strategies among Chinese psychiatric nurses.
AB  - PURPOSE: This study was conducted with Chinese psychiatric nurses to identify
      their workplace stressors and coping strategies, as well as the relationships
      between their demographics, workplace stressors, and coping strategies. DESIGN
      AND METHODS: This survey was conducted, with the use of three questionnaires, on
      188 psychiatric nurses recruited via convenient sampling in central China.
      FINDINGS: The findings indicated that (a) workload and dealing with death/dying
      were the greatest workplace stressors; (b) positive coping strategies were the
      most often used coping strategies; and (c) a series of correlation results
      occurred. PRACTICE APPLICATION: Understanding the relationship between workplace
      stressors, effective and ineffective coping, and demographics can contribute to
      designing less stressful environments and more constructive coping strategies.

PMID- 18826461
TI  - Strategies used by advanced practice psychiatric nurses in treating adults with
      depression.
AB  - PURPOSE: Strategies used by psychiatric advanced practice registered nurses
      (APRNs) in treating clients with depression are described to explore their
      effectiveness. DESIGN AND METHODS: Ten APRNs participated in semistructured
      individual interviews for this qualitative descriptive study. The use of either a
      symptom severity scale or symptom reduction checklist was used to measure the
      effectiveness of the strategies used. FINDINGS: APRNs identified a
      biopsychosocial approach as the primary component of their treatment of clients
      with depression. Other strategies identified include psychopharmacology,
      cognitive-behavioral therapy, and partnering with the client. PRACTICE
      IMPLICATIONS: Treatment of depression can be enhanced with the incorporation of
      the biopsychosocial strategies along with standard treatment modalities.

PMID- 18826462
TI  - Comparability between telephone and face-to-face structured clinical interview
      for DSM-IV in assessing social anxiety disorder.
AB  - PURPOSE: This article evaluates the comparability of the telephone and in-person
      Structured Clinical Interview for DSM-IV (SCID) interviews in assessing patients
      with social anxiety disorder (SAD) as an independent anxiety diagnosis. DESIGN
      AND METHODS: One hundred subjects were randomly selected and interviewed with the
      SCID, once by telephone and once in person (1-3 months later). FINDINGS: The
      prevalence of SAD assessed with the telephone interviews was 56%, whereas the in
      person prevalence was 52%, with no statistically significant difference. The test
      retest kappa for the 200 interviews was .84, indication of excellent agreement.
      PRACTICE IMPLICATIONS: These findings, along with the existing evidence of their
      validity, should encourage the use of SCID by telephone for SAD diagnostic
      interviews.

PMID- 18826463
TI  - Improving the role of nursing in the treatment of depression in primary care in
      Spain.
AB  - PURPOSE: We describe a multicomponent program for the systematic evaluation and
      treatment of depression in primary care. CONCLUSION: Primary-care nurses trained
      in clinical and therapeutic aspects of depression play a central role in care
      management, patient education, treatment adherence, and clinical monitoring.
      PRACTICE IMPLICATIONS: Diverse interventions, including organizational changes
      and the enhancement of the role of nurses, have been effective in improving
      depression outcomes in primary-care settings.

PMID- 18826464
TI  - 22q11 deletion syndrome: is that what they used to call . . . ?
AB  - PURPOSE: 22q11 deletion syndrome (22q11DS) is a very common, but commonly
      overlooked, disorder that has many variable features, such as serious heart
      defects, speech and articulation problems, immune compromise, learning problems,
      pervasive developmental disorders, and a late appearing phenotype of this
      condition--mental illness. CONCLUSION: Persons with 22q11DS are likely to be
      medically complex patients with pervasive developmental disorders and late
      appearing mental problems. PRACTICE IMPLICATIONS: Establishing this diagnosis is
      useful to families and healthcare providers to anticipate and address immediate
      and future issues surrounding health promotion, disease prevention, and health
      maintenance.

PMID- 18826465
TI  - Postpartum bipolar depression: a case study.
AB  - PURPOSE: This case study of a 29-year-old married woman with postpartum bipolar
      depression demonstrates the importance of an accurate differential diagnosis when
      evaluating a patient presenting with symptoms of postpartum depression.
      CONCLUSION: Although many of the signs and symptoms of unipolar depression and
      bipolar depression are identical, there are some important differences. Careful
      evaluation of symptoms and a thorough psychiatric history leads to accurate
      diagnosis and successful treatment outcomes. PRACTICE IMPLICATIONS: All women
      presenting with postpartum depression should be screened for bipolar disorder as
      the treatment of bipolar depression differs substantially from unipolar
      depression.

PMID- 18826466
TI  - Self-reported psychopathological symptoms and quality of life in outpatients with
      bipolar disorder.
AB  - PURPOSE: Patients with bipolar disorder in a euthymic mood state can suffer from
      subsyndromal or residual symptoms of depression or hypomania. This study was
      undertaken to gain insight into the broader spectrum of psychopathological
      symptoms and quality of life. DESIGN AND METHODS: Participants (n = 157)
      completed the Symptoms Checklist-90, the World Health Organization Quality of
      Life Assessment Instrument-Bref, and a questionnaire addressing demographic and
      clinical characteristics. FINDINGS: Outpatients with bipolar disorder reported
      fewer symptoms of psychopathology than psychiatric outpatients in general, but
      relative to the general population, a significantly lower quality of life was
      reported. The number of symptoms showed consistently negative correlations with
      the quality of life. PRACTICE IMPLICATIONS: The results of this study urge nurses
      to not settle for treatment response in terms of reduced manic or depressive
      episodes, but instead to strive for full remission of all symptoms.

PMID- 18826467
TI  - Cytokines and their role in depression.
AB  - PURPOSE: This study aims to review the cytokines that mediate the inflammatory
      process, the interleukins and the interferons, and the interaction of cytokines
      with serotonin as causative factors in the role of depression. CONCLUSIONS:
      Administration of proinflammatory cytokines to treat medical diseases induces
      depressive symptoms in humans. Patients diagnosed with depression tend to have
      high levels of cytokine activity and impaired immune response, as well as those
      patients suffering from inflammatory processes. Proinflammatory cytokines
      interfere with the body's feedback loop to reduce circulating corticosteroids
      during the stress response. PRACTICE IMPLICATIONS: Serotonin levels, integrally
      associated with depression, are lowered when levels of circulating cytokines are
      high when the precursor tryptophan is reduced.

PMID- 18826468
TI  - Biological perspectives irreversible lithium-induced neuropathy: two cases.

PMID- 18826469
TI  - Perspectives in psychiatric consultation liaison nursing: the role of the
      psychiatric consultation liaison nurse in initiating collaborative nursing
      research.

PMID- 18826472
TI  - Valosin-containing protein/p97 interacts with sperm-activating and sperm
      attracting factor (SAAF) in the ascidian egg and modulates sperm-attracting
      activity.
AB  - Sperm chemotaxis toward an egg is observed in many animals, and the control of
      sperm-attracting activity is thought to play an important role in ensuring
      fertilization. However, the mechanism underlying the release of a sperm
      attractant from an egg is still obscure. In this study, we examined the systems
      involved in the release of sperm-activating and sperm-attracting factor (SAAF),
      which is the sperm attractant of the ascidian Ciona intestinalis. Here, we show
      that the egg acquires sperm-attracting activity after germinal vesicle breakdown.
      Further, since the cytoplasmic extracts of immature oocytes exhibit no sperm
      attracting activity, the SAAF in oocytes may be activated after germinal vesicle
      breakdown. We found 13 SAAF-binding proteins in an egg plasma membrane extract
      and identified five proteins by proteomic analysis: valosin-containing protein
      (VCP)/p97, proteasome alpha 2 subunit, MGC97756 protein, proteasome subunit Y,
      and beta-tubulin. In particular, the interaction between VCP/p97 and SAAF was
      confirmed by a pull-down assay. VCP/p97 is initially localized in the germinal
      vesicle, and during oocyte maturation, it shifts to the endoplasmic reticulum in
      the cortical regions. Thus, VCP/p97 is a potential modulator of SAAF release from
      the egg.

PMID- 18826473
TI  - Initial observation of potential factors involved in the specification process of
      oral-aboral axis in the sand dollar Scaphechinus mirabilis.
AB  - To elucidate factors involved in the oral-aboral axis specification, several
      observations and experiments were undertaken using the sand dollar Scaphechinus
      mirabilis. Unlike in Strongylcentrotus purpuratus, localization of mitochondria
      was not detected in unfertilized eggs. After fertilization, however, the bulk of
      mitochondria became localized to the opposite side of sperm entry. The first
      cleavage divided this mitochondrial cluster into daughter blastomeres. On the
      other hand, a second cleavage produced daughter blastomeres containing quite
      different amounts of mitochondria. To know whether such mitochondrial
      localization affects the oral-aboral axis specification, 4-cell-stage embryos
      were separated along the second cleavage plane. Although both half embryos
      developed into morphologically normal plutei, some differences, such as the
      number of pigment cells, were noticed between the siblings. In contrast, cell
      tracing revealed that the first cleavage separated the oral from the aboral part
      in most cases, indicating that the unequal distribution of mitochondria is not
      critical for the oral-aboral axis specification. Further, stained and non-stained
      half embryo fragments were combined. Such combined embryos developed into normal
      plutei with a single oral-aboral axis. The plane dividing labeled and non-labeled
      parts were incident, oblique or perpendicular to the median plane of the combined
      embryo, and the appearance frequencies of those labeling patterns were similar to
      those obtained by cell tracing in intact embryos. Interestingly, the half
      fragments derived from embryos inseminated earlier showed a tendency to form the
      oral part. These suggest that several factors as well as the localized
      cytoplasmic components would be involved in the specification process of oral
      aboral axis.

PMID- 18826474
TI  - Neoblast-enriched fraction rescues eye formation in eye-defective planarian
      'menashi' Dugesia ryukyuensis.
AB  - Planarians are well known for their remarkable regenerative capacity. This
      capacity to regenerate is thought to be due to the presence of totipotent somatic
      stem cells known as 'neoblasts', which have particular morphological
      characteristics. The totipotency of neoblasts was supported by Baguna's
      experiment, which involved the introduction of donor cells into irradiated hosts.
      However, since Baguna's experiment did not include the use of a phenotypic
      marker, the donor cells could not be traced. In the current study, a genetic
      mutant planarian, menashi, an eye-defective mutant that lacks the pigmented area
      in the eyes, was established. This planarian is excellent for tracing the fate of
      cells after their introduction into irradiated hosts. To investigate the
      differentiation potency more directly, a neoblast-rich fraction obtained from
      normal worms was transplanted into an X-ray-irradiated menashi strain. Planarians
      that survive X-ray irradiation were developed, and we observed the pigment of the
      area in the eyes of the regenerating planarians. This result suggests that the
      neoblast-rich fraction contains cells that can proliferate and differentiate.
      These cells can replace the cells and structures lost by X-ray irradiation and
      ablation, and they can also differentiate into eye pigment cells.

PMID- 18826475
TI  - Tracing retinal fiber trajectory with a method of transposon-mediated genomic
      integration in chick embryo.
AB  - We report convenient retinal fiber tracing by transfecting the tracer cDNA by in
      ovo electroporation. Long-term and stable expression of tracer proteins such as
      green fluorescent protein is achieved by transposon-mediated genome integration
      of the tracer protein expression cassette. We carried out coelectroporation of a
      plasmid containing CAGGS-tracer cDNA flanked by the Tol2 transposable element
      along with a transposase expression vector to the optic vesicle of chick embryos
      at stage 11. By selecting electrodes, we can label a large group of retinal
      ganglion cells, or a small group of retinal ganglion cells; parallel electrodes
      assure transfection of large areas of the retina, and needle type electrodes
      label small areas of the retina. The retinal fiber trajectory and terminal zone
      (TZ) could be detected in the precise retinotopic manner on the contra-lateral
      side of the optic tectum. The method has advantage in that we can show the
      retinal fiber trajectory in relation to the molecules that are responsible for
      pathfinding for the retinal fibers in the same specimen.

PMID- 18826476
TI  - A translational view on urinary tract infection.

PMID- 18826477
TI  - TLR- and CXCR1-dependent innate immunity: insights into the genetics of urinary
      tract infections.
AB  - The susceptibility to urinary tract infection (UTI) is controlled by the innate
      immune response and Toll like receptors (TLRs) are the sentinels of this
      response. If productive, TLR4 signalling may initiate the symptomatic disease
      process. In the absence of TLR4 signalling the infected host instead develops an
      asymptomatic carrier state. The activation of mucosal TLR4 is also influenced by
      the properties of the infecting strain, and pathogens use their virulence factors
      to trigger 'pathogen-specific' TLR4 responses in the urinary tract but do not
      respond to the asymptomatic carrier strains in patients with asymptomatic
      bacteriuria (ABU). The TLR4 dependence has been demonstrated in mice and the
      relevance of low TLR4 function for protection for human disease was recently
      confirmed in children with asymptomatic bacteriuria, who expressed less TLR4 than
      age matched controls. Functional chemokines and functional chemokine receptors
      are crucial for neutrophil recruitment, and for the neutrophil dependent
      bacterial clearance. Interleukin (IL)-8 receptor deficient mice develop acute
      septic infections and chronic tissue damage, due to aberrant neutrophil function.
      This mechanism is relevant for human UTI as pyelonephritis prone children express
      low levels of the human CXCL8 (Il-8) receptor, CXC chemokine receptor 1 (CXCR1)
      and often have heterozygous CXCR1 polymorphisms. This review illustrates how
      intimately the innate response and the susceptibility to UTI are linked and
      sophisticated recognition mechanisms that rely on microbial virulence and on host
      TLR4 and CXCR1 signalling.

PMID- 18826478
TI  - Innate and adaptive immune responses in the urinary tract.
AB  - As new and intriguing details of how uropathogens initiate infections and persist
      within the urinary tract have emerged, so has important information regarding how
      the immune system functions within the urinary tract. Recent studies have
      revealed the existence of a multifaceted innate immune response triggered by Toll
      like receptor (TLR) 4 on superficial bladder epithelial cells directed at
      clearing infection by Gram negative pathogens. Other studies have reported that
      the adaptive immune response in the urinary tract is effective and that vaccines
      comprised of bacterial virulence factors or whole dead bacteria can evoke
      protective immunity against urinary tract infections (UTIs) in animals and
      humans. As antibiotic therapy becomes increasingly ineffective, modulating the
      innate and adaptive immune system in the urinary tract using TLR4 ligands and
      other immunomodulators may become viable options to combat UTIs.

PMID- 18826479
TI  - Current concepts of molecular defence mechanisms operative during urinary tract
      infection.
AB  - Mucosal tissues such as the gastrointestinal tract are typically exposed to a
      tremendous number of microorganisms and many of them are potentially dangerous to
      the host. In contrast, the urogenital tract is rather infrequently colonized with
      bacterial organisms and also devoid of physical barriers as a multi-layered mucus
      or ciliated epithelia, thereby necessitating separate host defence mechanisms.
      Recurrent urinary tract infection (UTI) represents the successful case of
      microbial host evasion and poses a major medical and economic health problem.
      During recent years considerable advances have been made in our understanding of
      the mechanisms underlying the immune homeostasis of the urogenital tract. Hence,
      the system of pathogen-recognition receptors including the Toll-like receptors
      (TLRs) is able to sense danger signalling and thus activate the host immune
      system of the genitourinary tract. Additionally, various soluble antimicrobial
      molecules including iron-sequestering proteins, defensins, cathelicidin and Tamm
      Horsfall protein (THP), as well as their role for the prevention of UTI by
      modulating innate and adaptive immunity, have been more clearly defined.
      Furthermore, signalling mediators like cyclic adenosine monophosphate (cAMP) or
      the circulatory hormone vasopressin were shown to be involved in the defence of
      uropathogenic microbes and maintenance of mucosal integrity. Beyond this,
      specific receptors e.g. CD46 or beta1/beta 3-integrins, have been elucidated that
      are hijacked by uropathogenic E. coli to enable invasion and survival within the
      urogenital system paving the way for chronic forms of urinary tract infection.
      Collectively, the majority of these findings offer novel avenues for basic and
      translational research implying effective therapies against the diverse forms of
      acute and chronic UTI.

PMID- 18826480
TI  - Pathways of renal injury in systemic gram-negative sepsis.
AB  - Acute renal failure is a grave complication of systemic gram-negative sepsis. The
      pathophysiological mechanisms of sepsis leading to kidney injury result in part
      from systemic inflammatory and haemodynamic alterations. These are triggered by
      the interaction of endotoxin with Toll-like receptor 4 (TLR4) on cells of the
      immune system. Recently, TLR4 and other co-effector molecules were identified on
      renal tubular and vascular cells. Furthermore, it was demonstrated that systemic
      endotoxin has direct access to renal sites where these receptors are expressed.
      Therefore, we review data in support of this novel pathway of renal injury in
      sepsis, whereby systemic endotoxin causes direct injury through interactions with
      local epithelial and endothelial TLR4.

PMID- 18826481
TI  - Therapeutic challenges of urosepsis.
AB  - Urosepsis accounts for approximately 25% of all sepsis cases and may develop from
      a community or nosocomial acquired urinary tract infection (UTI). The underlying
      UTI is almost exclusively a complicated one with involvement of parenchymatous
      urogenital organs (e.g. kidneys, prostate). In urosepsis, as in other types of
      sepsis, the severity of sepsis depends mostly upon the host response. The
      treatment of urosepsis comprises four major aspects: Early goal directed therapy,
      early optimal pharmacodynamic exposure to antimicrobials, early control of the
      complicating factor in the urinary tract and specific sepsis therapy. Following
      these prerequisites there appear two major challenges that need to be addressed:
      Firstly, time from admission to therapy is critical; the shorter the time to
      effective treatment, the higher the success rate. This aspect has to become
      incorporated into the organisational process. Secondly, adequate initial
      antibiotic therapy has to be insured. This goal implies however, a wide array of
      measures to ensure rational antibiotic policy. Both challenges are best targeted
      if an interdisciplinary approach at any level of the process is established,
      encompassing urologists, intensive care specialists, radiologists,
      microbiologists and clinical pharmacologists working tightly together at any
      time.

PMID- 18826482
TI  - Asymptomatic bacteriuria and symptomatic urinary tract infections in pregnancy.
AB  - Symptomatic and asymptomatic bacteriuria is common in pregnant women. A history
      of previous urinary tract infections and low socioeconomic status are risk
      factors for bacteriuria in pregnancy. Escherichia coli is the most common
      aetiologic agent in both symptomatic and asymptomatic infection and quantitative
      culture is the gold standard for diagnosis. Treatment of asymptomatic bacteriuria
      has been shown to reduce the rate of pyelonephritis in pregnancy and therefore
      screening for and treatment of asymptomatic bacteriuria has become a standard of
      obstetrical care. Antibiotic treatment of asymptomatic bacteriuria is associated
      with a decrease in the incidence of low birth weight, but the methodological
      quality of the studies limits the strength of the conclusions that can be drawn.
      Debate exists in the literature as to whether treated pyelonephritis is
      associated with adverse fetal outcomes. There is no clear consensus in the
      literature on antibiotic choice or duration of therapy for infection. With
      increasing antibiotic resistance, consideration of local resistance rates is
      necessary when choosing therapy.

PMID- 18826483
TI  - Urinary tract infection in renal transplant recipients.
AB  - Urinary tract infection (UTI) is common in renal transplant recipients. Frequency
      of UTIs depend on many factors such as age, female gender, kidney function, co
      morbidity, type and amount of immunosuppression, urological instrumentation
      and/or the follow-up period (short term or long term) after kidney
      transplantation. UTI may worsen graft and patient survival. A significant
      proportion of renal transplant recipients with UTIs may develop acute
      pyelonephritis (APN), which is an independent risk factor for deterioration of
      graft function. Renal transplant recipients with UTIs are often clinically
      asymptomatic as a consequence of immunosuppression. UTI, however, may progress to
      APN (particularly in the early post-transplant period), bacteraemia and the full
      blown picture of urosepsis. Strategies for long term prophylaxis and
      antimicrobial treatment of UTI in renal transplant recipients are discussed.

PMID- 18826484
TI  - The relationship between pyridine nucleotides and seed dormancy.
AB  - To investigate the proposed role for NAD metabolism in regulating seed dormancy,
      NAD metabolites and associated enzyme activities were analysed in seed of
      Arabidopsis thaliana ecotypes ranging from Col-0, which has low seed dormancy, to
      Cvi, which is highly dormant. Seed poly(ADP-ribosyl)ation levels did not
      correlate well with the depth of seed dormancy but did correlate with the
      sensitivity of germination to the DNA damaging agent MMS. Cvi seed had relatively
      high NAD and low NADP levels compared with the less dormant ecotypes and the NAD
      : NADP ratios correlated well with dormancy. The activity of NAD kinase was
      relatively low, and NADP phosphatase was relatively high in dormant Cvi seed,
      indicating that these enzymes may be involved in controlling the NAD : NADP
      ratio. Dormant fresh Cvi and nondormant after-ripened Cvi seeds were used to
      investigate further. Measurement of reduced and oxidised pyridine nucleotides
      indicated that breaking of dormancy was associated with a reduction in NAD levels
      but not with an increase in NADP levels. It is proposed that poly(ADP-ribose)
      polymerase is involved in protecting the seed from genotoxic stress, whereas the
      level of NAD affects the depth of dormancy, perhaps by enhancing abscisic acid
      (ABA) synthesis.

PMID- 18826485
TI  - The glutathione peroxidase gene family of Lotus japonicus: characterization of
      genomic clones, expression analyses and immunolocalization in legumes.
AB  - Despite the multiple roles played by antioxidants in rhizobia-legume symbioses,
      little is known about glutathione peroxidases (GPXs) in legumes. Here the
      characterization of six GPX genes of Lotus japonicus is reported. Expression of
      GPX genes was analysed by quantitative reverse transcription-polymerase chain
      reaction in L. japonicus and Lotus corniculatus plants exposed to various
      treatments known to generate reactive oxygen and/or nitrogen species. LjGPX1 and
      LjGPX3 were the most abundantly expressed genes in leaves, roots and nodules.
      Compared with roots, LjGPX1 and LjGPX6 were highly expressed in leaves and LjGPX3
      and LjGPX6 in nodules. In roots, salinity decreased GPX4 expression, aluminium
      decreased expression of the six genes, and cadmium caused up-regulation of GPX3,
      GPX4 and GPX5 after 1 h and down-regulation of GPX1, GPX2, GPX4 and GPX6 after 3
      24 h. Exposure of roots to sodium nitroprusside (a nitric oxide donor) for 1 h
      increased the mRNA levels of GPX4 and GPX6 by 3.3- and 30-fold, respectively.
      Thereafter, the GPX6 mRNA level remained consistently higher than that of the
      control. Immunogold labelling revealed the presence of GPX proteins in root and
      nodule amyloplasts and in leaf chloroplasts of L. japonicus and other legumes.
      Labelling was associated with starch grains. These results underscore the
      differential regulation of GPX expression in response to cadmium, aluminium and
      nitric oxide, and strongly support a role for GPX6 and possibly other GPX genes
      in stress and/or metabolic signalling.

PMID- 18826486
TI  - Review article: The role of adipose tissue in uraemia-related insulin resistance.
AB  - Adipose tissue is no longer considered to be an inert tissue of which function is
      to store fat. It actively secretes a number of biologic active compounds that are
      involved in the regulation of many processes like food intake, energy
      expenditure, metabolism homeostasis, immunity and blood pressure homeostasis.
      General metabolism alteration in patients with chronic kidney disease has a
      profound impact on biology of adipocytes. Chronic renal failure is a pathological
      condition, of which two major hallmarks are chronic inflammation and insulin
      resistance. In uraemic patients, adipose tissue became an important source of
      molecules that are responsible, at least in part, for the metabolic disturbances
      seen in these patients. Some of these molecules act as pro-inflammatory agents
      contributing to the maintenance and enhancement of the chronic inflammatory
      response. These pro-inflammatory molecules, along with other molecules secreted
      by the adipose tissue, have a central position in the aetiology of uraemia
      associated insulin resistance. In this review, we intend to summarize some
      aspects of the biology of adipokines in uraemia, with emphasis on the link
      between these molecules and insulin resistance.

PMID- 18826487
TI  - Associations of interleukin-6, C-reactive protein and serum amyloid A with
      mortality in haemodialysis patients.
AB  - BACKGROUND: Individuals with end-stage renal disease (ESRD) manifest a chronic
      inflammatory state. Serum albumin, C-reactive protein (CRP), interleukin-6 (IL-6)
      and serum amyloid A (SAA) have been associated with mortality in ESRD, although
      reports vary as to whether they are true independent markers of mortality. We
      undertook a prospective study to determine whether these markers could predict
      mortality in ESRD. METHODS: A cohort of individuals on haemodialysis was followed
      prospectively for a mean of 2.1 years. Albumin, CRP, IL-6 and SAA were drawn at
      enrollment. Association between mortality and serum markers was assessed using
      Cox proportional hazards regression. A trend analysis was undertaken to establish
      the functional form of the association between serum markers and outcome.
      RESULTS: After multivariable adjustment, IL-6 was most strongly associated with
      mortality, followed closely by albumin (P = 0.0002 and P = 0.0005, respectively).
      CRP was marginally associated with mortality (P = 0.046), and SAA was not
      independently associated with mortality. In the final model adjusting for the
      effects of both IL-6 and albumin simultaneously, both markers remained associated
      with mortality (P = 0.003 and P = 0.011). CONCLUSION: IL-6 had the strongest
      independent association with mortality, followed closely by albumin. CRP and SAA
      were not associated with mortality when measured at single time points.
      Increasing levels of IL-6 and decreasing levels of albumin were associated with
      increased mortality. IL-6 and albumin may be capturing different aspects of the
      inflammatory burden observed in haemodialysis patients.

PMID- 18826488
TI  - Perindopril attenuates tubular hypoxia and inflammation in an experimental model
      of diabetic nephropathy in transgenic Ren-2 rats.
AB  - BACKGROUND: Renal hypoxia plays a role in the development of diabetic
      nephropathy, and may be mediated by overactivity of the renin-angiotensin
      aldosterone system (RAAS). In this study the localization of cellular hypoxia in
      an experimental model of diabetic nephropathy was assessed, and the effect of the
      angiotensin-converting enzyme inhibitor perindopril on hypoxia evaluated.
      METHODS: Female Sprague-Dawley rats heterozygous for the Ren-2 gene were
      randomized to three groups (n = 8 per group)--controls, diabetes or diabetes +
      perindopril. Diabetes was induced by injection of streptozotocin at 6 weeks of
      age. Perindopril was administered at a dose of 2 mg/kg daily from 6 weeks.
      Subjects were culled after 16 weeks. Areas of tissue hypoxia were localized using
      immunohistochemistry to detect pimonidazole uptake. RESULTS: Diabetic rat kidneys
      were characterized by increases in tubulointerstitial collagen deposition
      compared with controls. Tubular hypoxia was significantly greater in diabetic
      rats, indicated by a 2.5-fold increase in the proportional area of pimonidazole
      immunostaining (P < 0.001). Immunohistochemical staining for pimonidazole co
      localized with osteopontin, and was associated with higher numbers of ED-1
      positive cells (macrophages) within the tubulointerstitium. Treatment with
      perindopril ameliorated structural changes of diabetic nephropathy and reduced
      the amount of pimonidazole and ED-1 immunostaining to levels similar to that of
      controls. CONCLUSION: In diabetic Ren-2 rats the development of diabetic
      nephropathy was associated with tubular hypoxia. Co-localization of osteopontin
      with hypoxic cells suggests that tubular hypoxia may be involved in the
      pathogenesis of diabetic nephropathy. The degree of hypoxia and fibrosis was
      attenuated by treatment with perindopril.

PMID- 18826489
TI  - MT3/QR2 melatonin binding site does not use melatonin as a substrate or a co
      substrate.
AB  - Quinone reductase 2 (QR2, E.C. 1.10.99.2) is implicated in cell reactive oxygen
      species production. The catalytic activity of this enzyme is inhibited by 1
      microM of melatonin. QR2 was identified as the third melatonin binding site
      (MT3). It is of major importance to understand the exact roles of melatonin and
      QR2 in oxidative stress. A fascinating possibility that melatonin could serve as
      a co-substrate or substrate of QR2 was hypothesized recently. In the current
      investigation, nuclear magnetic resonance studies of the QR2 catalytic reaction
      were performed, the results led us to conclude that, whatever the conditions,
      melatonin is not cleaved off to form N1-acetyl-N2-formyl-5-methoxykynurenine by a
      catalytically active QR2, very strongly indicating that melatonin is neither a
      substrate nor a co-substrate of this enzyme. Further studies are needed in order
      to better understand the relationship between MT3/QR2, melatonin and redox status
      of the cells, in order to better explain the anti-oxidant activities of melatonin
      at pharmacological concentrations (>1 microM).

PMID- 18826490
TI  - Cognitive outcome in children and adolescents treated for acute lymphoblastic
      leukaemia with chemotherapy only.
AB  - OBJECTIVE: To examine cognitive outcome in children and adolescents with acute
      lymphoblastic leukaemia (ALL) in remission, treated with central nervous system
      prophylactic chemotherapy only. METHOD: Thirty-five children and adolescents, age
      8.4-15.3 years in long-term remission from ALL, 4.2-12.4 years post diagnosis,
      without relapse and no pre-diagnosis history of neurodevelopmental disorder were
      compared with 35 healthy controls matched for gender and age, on measures of
      intellectual functioning Wechsler Intelligence Scale for Children-Third Edition
      (WISC-III). RESULTS: All but two of the ALL survivors treated by chemotherapy
      only obtained WISC-III Total Intelligence Quotient (IQ) scores in the normal
      range (M = 95.3), but their scores were significantly below levels for their
      matched controls and below normative standards for WISC-III. The difference
      between patients and controls was significant at the p < 0.001 level for the
      following measures: Total IQ, Verbal IQ, Verbal Comprehension Index, Freedom from
      Distraction Index and three verbal subtest scores. CONCLUSION: The results
      indicate long-term sequelae in global cognitive functions, and indicate that
      verbal function, processing speed, attention and complex visual-spatial problem
      solving may be affected in the chemotherapy only group.

PMID- 18826491
TI  - Acoustic cry characteristics of infants exposed to methadone during pregnancy.
AB  - OBJECTIVE: Infant cry characteristics reflect the neurological and medical status
      of the infant. This study compared the acoustic cry characteristics of infants
      born to mothers maintained on methadone during pregnancy with those of infants
      not exposed to methadone during pregnancy. METHODS: At 42 weeks of post-menstrual
      age, 89 crying episodes ranging in duration from 1.15 to 1.97 sec were collected
      from 10 methadone-exposed (ME) and 10 non-methadone-exposed (NE) infants. Cry
      utterances were analysed acoustically using spectrographic displays and measures
      of cry utterance duration and fine-grained analyses of the fundamental frequency
      calculated for each cry. RESULTS: No between-group differences were found on
      measures of cry duration or fundamental frequency. However, analyses of frequency
      perturbation showed that the cry utterances of ME infants were characterized by
      significantly higher levels of frequency perturbation than the cries of infants
      not exposed to methadone. These effects largely persisted after statistical
      control for the confounding effects of other maternal drug use during pregnancy.
      CONCLUSION: The crying behaviour of infants exposed prenatally to the synthetic
      opiate, methadone, is characterized by higher levels of vocal fold vibratory
      perturbation than NE infants. These findings suggest the possibility of early,
      subtle neurological vulnerability in this high-risk group of infants.

PMID- 18826492
TI  - Low-carbohydrate (low & high-fat) versus high-carbohydrate low-fat diets in the
      treatment of obesity in adolescents.
AB  - AIM: To compare the impact of low-carbohydrate diets of different fat content to
      high-carbohydrate low-fat diet on weight and metabolic parameters in obese
      adolescents. METHODS: Fifty-five patients aged 12-18 years with a body mass index
      (BMI) above the 95th percentile were randomly allocated to one of three
      isoenergetic diet regimens. Anthropometric and metabolic measurements were taken
      after overnight fast, at baseline, after the 12-week intervention and after nine
      month of follow-up. RESULTS: No significant differences were found among the
      groups in changes in BMI, BMI-percentile, fat percentage, or metabolic markers at
      the end of the intervention and at the end of follow-up. Insulin level and
      homeostasis model assessment (HOMA) level decreased significantly at both time
      points only in the two low carbohydrate diet groups. CONCLUSION: All diet
      regimens are associated with a significant reduction in BMI and improvement of
      some metabolic parameters in obese adolescents. Low-carbohydrate diets apparently
      have no advantage over high-carbohydrate low-fat diets. The significant drop in
      insulin level and HOMA in the low carbohydrate diet groups is noteworthy given
      the increasing frequency of type-2 diabetes as part of metabolic syndrome in
      children and youth. The impact of low carbohydrate diets in obese and insulin
      resistant youth warrants further investigation.

PMID- 18826493
TI  - Pitfalls in the design and analysis of paediatric clinical trials: a case of a
      'failed' multi-centre study, and potential solutions.
AB  - AIM: To increase awareness of possible pitfalls in the design and analysis of a
      multi-centre randomized clinical trial and to give an overview of alternative
      study designs and their consequences for power analyses in case of limited
      availability of trial participants. METHODS: Investigation of the assumptions in
      the power calculation and re-analysis of the original data of a 'failed' trial on
      the effect of dexamethasone on the duration of mechanical ventilation in young
      children with respiratory syncytial virus infection. Use of 'boundaries approach'
      is explored using the data from this trial. A comprehensive overview of the
      various modern solutions for the design of a subsequent trial in this field is
      given. RESULTS: Two frequent major deficiencies of trial design and data analysis
      are reviewed in depth, i.e. too optimistic assumptions for the sample size
      calculation and failure to adjust for centre effects. CONCLUSION: Critical review
      of trial assumptions and if necessary sample size recalculation based on an
      internal pilot by a data monitoring committee is recommended to maximize the
      probability of obtaining conclusive results.

PMID- 18826494
TI  - Trends in the prevalence of low birth weight in Okinawa, Japan: a public health
      perspective.
AB  - AIM: To review the trends in low birth weight (LBW) in Japan and Okinawa and to
      discuss the public health implications of the trend. METHODS: The statistical
      records of Japan and the Okinawa prefecture were reviewed to observe secular
      trends of LBW incidence rate and other health indicators. Literature researches
      were undertaken of English and Japanese language publications to complete the
      review. RESULTS: The LBW rate in Japan declined until the 1970s, reaching a low
      point for the whole country in 1978-1979 when it was 5.2% (7.2% in Okinawa). In
      Okinawa the proportion of LBW declined from 8.1% in 1973 to 7.2 in 1978. Since
      1980 the LBW rate has steadily increased to its current level of 9.3% in Japan
      and 10.9% in Okinawa. During this period, the prematurity rate has not increased
      and other indicators of child health have continued to improve. CONCLUSION: Japan
      is unique among developed countries in that the LBW rate has almost doubled in
      the past three decades and the rate in Okinawa is 20% greater than the mainland.
      The health costs of this trend include the neonatal care of LBW infants and the
      increased risk of chronic disease in later life.

PMID- 18826495
TI  - Toll-like receptor 4 Asp299Gly and Thr399Ile polymorphisms in gastric cancer of
      intestinal and diffuse histotypes.
AB  - In the present study we investigated the potential role of Toll-like receptor 4
      (TLR-4) Asp299Gly and Thr399Ile polymorphisms as risk factors in the development
      of gastric cancer. TLR-4 Asp299Gly and Thr399Ile polymorphisms were investigated
      in 171 Italian patients with sporadic gastric cancer and in 151 controls.
      Unconditional regression (odds ratio and 95% confidence intervals) were used to
      investigate the association of the studied polymorphisms with gastric cancer. TLR
      4 Thr399Ile polymorphism is linked with an increased susceptibility to gastric
      cancer (P = 0.023 and hazard ratio = 3.62). No significant association for TLR-4
      Asp299Gly polymorphism was found. In the subgroup of patients with intestinal
      type gastric cancer, a significant risk of gastric cancer was associated with TLR
      4 Thr399Ile genotype (P = 0.006). Our results demonstrated that TLR-4 Thr399Ile
      polymorphism is linked with an increased susceptibility to gastric cancer. An
      increased risk for intestinal gastric cancer in carriers of the TLR4 Thr399Ile
      allele was observed. Future epidemiological studies should consider the possible
      interactions between proinflammatory genotypes (such as TLR and interleukin-1R
      polymorphisms) and other risk factors for cancer such as dietary habits and/or
      exposure to environmental carcinogens.

PMID- 18826496
TI  - Single cell analysis of B lymphocytes from Wegener's granulomatosis: B cell
      receptors display affinity maturation within the granulomatous lesions.
AB  - Increased amounts of anti-neutrophil cytoplasm antibody (ANCA) directed against
      proteinase 3 (PR3) are a diagnostic and pathogenic hallmark of full-blown
      Wegener's granulomatosis (WG). Aggregates of B lymphocytes proximal to PR3+ cells
      as well as plasma cells have been described as substantial components of
      Wegener's granuloma and could participate in forming tertiary lymphoid
      structures, which might promote autoantibody formation. Our aim was a molecular
      analysis of single B cells in order to develop a methodological approach that
      allows examination of potential ANCA formation in the tissue. Single B cells from
      cryo-conserved endonasal biopsies of three WG patients were isolated, using laser
      assisted microdissection. Subsequently, their immunoglobulin variable heavy (VH)
      and light (Vkappa, Vlambda) chain genes were analysed by single cell polymerase
      chain reaction and direct sequencing. Sixteen immunoglobulin VH-Vkappa or VH
      Vlambda chain gene couples were characterized. Twelve of these immunoglobulin
      gene couples resembled memory B cells. Two offsprings of one B cell were
      detected, indicating clonal expansion. VH genes representing 39 single B cells of
      WG tissues displayed significantly more mutations when compared with VH genes
      from peripheral blood of a healthy donor. The findings confirm and extend our
      previous results, arguing for an initial selection and affinity maturation of B
      cells within Wegener's granuloma. Further, the methodology provides the initial
      basis for the recombinant generation of antibodies derived from tissue cells.

PMID- 18826497
TI  - Clinical relevance of multiple antibody specificity testing in anti-phospholipid
      syndrome and recurrent pregnancy loss.
AB  - We wanted to evaluate whether testing for anti-phosholipid antibodies other than
      anti-cardiolipin (aCL) and anti-beta-2 glycoprotein I (abeta2GPI) immunoglobulin
      (Ig)G and IgM identifies patients with recurrent pregnancy loss (RPL) who may be
      positive for anti-phospholipid syndrome (APS). In a cross-sectional study
      comprising 62 patients with APS, 66 women with RPL, 50 healthy blood donors and
      24 women with a history of successful pregnancies, we tested IgM and IgG
      antibodies to phosphatidic acid, phosphatidyl choline, phosphatidyl ethanolamine,
      phosphatidyl glycerol, phosphatidyl inositol and phosphatidyl serine with and
      without beta-2 glycoprotein I (beta2GPI) from a single manufacturer as well as
      aCL and abeta2GPI antibodies. Diagnostic accuracies of individual and combined
      anti-phospholipid (aPL) assays were assessed by computing sensitivities,
      specificities, positive predictive values and negative predictive values together
      with their 95% confidence intervals. There was a general trend for increased
      sensitivities in the presence of beta2GPI co-factor with significant effect for
      certain specificities. The overall combined sensitivity of the non-recommended
      aPL assays was not significantly higher than that of the aCL and aB2GPI tests.
      Multiple aPL specificities in RPL group is not significantly different from
      controls and therefore of no clinical significance.

PMID- 18826498
TI  - Non-response to infliximab may be due to innate neutralizing anti-tumour necrosis
      factor-alpha antibodies.
AB  - Infliximab is a chimeric anti-tumour necrosis factor (TNF)-alpha antibody that is
      therapeutic in many patients with inflammatory bowel disease. What causes certain
      patients not to respond is unknown. The question posed is whether innate anti-TNF
      alpha antibodies play any role in the response to infliximab. Blood was drawn
      prior to the initial dose of infliximab. Serum anti-TNF-alpha antibodies were
      quantitated by enzyme-linked immunosorbent assay (ELISA). Affinity-purified anti
      TNF-alpha antibodies were isolated from serum immunoglobulin G using TNF-alpha
      coated beads. The ability of these antibodies to induce apoptosis of macrophages
      was measured by annexin and propidium iodide staining. Changes in TNF receptor
      type 2 (TNFR2) expression and release were determined by immunofluorescence and
      ELISA respectively. TNF-alpha-neutralization was assessed by the reversal of the
      lytic actions of TNF-alpha on WEHI cells. The amounts of innate anti-TNF-alpha
      antibodies in the serum from infliximab responders versus non-responders were the
      same. Apoptosis of monocytes increased with infliximab and by several of the
      purified anti-TNF-alpha antibodies, but these findings did not vary with the
      patients' responses to infliximab. Effects of the anti-TNF-alpha antibodies on
      the expression of TNFR2 on monocytes and their release of soluble TNFR2 did not
      vary with the patients' responses to infliximab. However, the neutralizing
      capacity of these antibodies differed, with responders having antibodies that
      reduced only 47 +/- 4% of the TNF-alpha activity while those from non-responders
      reduced 70 +/- 5% of the TNF-alpha activity (P < 0.01). Non-responders have
      innate anti-TNF-alpha antibodies with greater neutralizing activity than
      antibodies from responders. Any TNF-alpha-mediated disease process would be
      neutralized by intrinsic antibodies, so that the disease is likely to be driven
      by non-TNF-alpha-mediated events.

PMID- 18826499
TI  - Interleukin-18-deficient mice exhibit diminished chronic inflammation and airway
      remodelling in ovalbumin-induced asthma model.
AB  - Interleukin (IL)-18, which is produced by activated monocytes/macrophages and
      airway epithelial cells, is suggested to contribute to the pathophysiology of
      asthma by modulating airway inflammation. However, the involvement of IL-18 on
      modulating chronic airway inflammation and airway remodelling, which are
      characterized in a refractory asthma model exposed to long-term antigen, has not
      been investigated sufficiently. We examined the role of IL-18 in chronic airway
      inflammation and airway remodelling by long-term antigen exposure. IL-18
      deficient and C57BL/6-wild-type mice were sensitized by ovalbumin (OVA) and were
      then exposed to aerosolized OVA twice a week for 12 weeks. We assessed airway
      inflammation by assessing the infiltration of cells into the airspace and lung
      tissues, and airway remodelling by airway mucus expression, peribronchial
      fibrosis and smooth muscle thickness. In IL-18-deficient mice, when exposed to
      OVA, the total cells and neutrophils of the bronchoalveolar lavage fluid (BALF)
      were diminished, as were the number of infiltrated cells in the lung tissues. IL
      18-deficient mice exposed to OVA after 12 weeks showed significantly decreased
      levels of interferon (IFN)-gamma, IL-13 and transforming growth factor (TGF)
      beta1 in the BALF. The airway hyperresponsiveness to acetyl-beta-methacholine
      chloride was inhibited in IL-18-deficient mice in comparison with wild-type mice.
      In addition, IL-18-deficient mice exposed to OVA had fewer significant features
      of airway remodelling. These findings suggest that IL-18 may enhance chronic
      airway inflammation and airway remodelling through the production of IFN-gamma,
      IL-13 and TGF-beta1 in the OVA-induced asthma mouse model.

PMID- 18826500
TI  - Prolonged exposure to inhaled nitric oxide transiently modifies tubular function
      in healthy piglets and promotes tubular apoptosis.
AB  - AIM: Inhaled nitric oxide (iNO) is a selective pulmonary vasodilator. We
      hypothesized that those piglets exposed to prolonged iNO react with a modified
      renal function. METHODS: Randomized, placebo-controlled exposure to 40 p.p.m. iNO
      (30 h) in piglets (n = 20). Plasma and urine were sampled during three periods
      (first and second 12 h periods, and finally a 6 h period). We measured urine
      volumes, plasma and urine electrolytes (UNa, UK, UCl), plasma creatinine and
      urea. We calculated creatinine clearance (Ccr), and fractional excretions of
      sodium and potassium (FENa, FEK) and urinary excretions of electrolytes (UENa,
      UEK, UECl). Haemodynamic data were recorded and renal tubular apoptosis detected.
      RESULTS: For the first 12 h, certain parameters significantly increased in the
      iNO group (mean +/- SD): UNa (mmol L(-1)), 87.7 (+/-35.0) vs. 39.3 (+/-22.9), UCl
      (mmol L(-1)) 80.4 (+/-32.8) vs. 48.0 (+/-26.7), FENa (%) 2.1 (+/-0.8) vs. 0.7 (+/
      0.5), FEK (%) 31.7 (+/-7.0) vs. 20.7 (+/-12.3), as well as UENa (mmol) 61.0 (+/
      21.1) vs. 27.6 (+/-17.9) and UECl (mmol) 57.3 (24.5) vs. 37.6 (29.0). These
      changes were absent in the second and third periods of the study. Significant
      differences in percentage of apoptotic cell nuclei in the renal cortex and
      medulla were found after iNO exposure: 39% vs. 15%. CONCLUSION: Exposure to 40
      p.p.m. iNO in healthy anaesthetized piglets has a transient natriuretic effect
      that disappears after 12 h. We also found evidence of renal tubular apoptosis
      promotion after 30 h of iNO.

PMID- 18826501
TI  - The role of caveolin-1 in cardiovascular regulation.
AB  - Caveolae are omega-shaped membrane invaginations present in essentially all cell
      types in the cardiovascular system, and numerous functions have been ascribed to
      these structures. Caveolae formation depends on caveolins, cholesterol and
      polymerase I and transcript release factor-Cavin (PTRF-Cavin). The current review
      summarizes and critically discusses the cardiovascular phenotypes reported in
      caveolin-1-deficient mice. Major changes in the structure and function of heart,
      lung and blood vessels have been documented, suggesting that caveolae play a
      critical role at the interface between blood and surrounding tissue. According to
      an emerging paradigm, many of these changes are secondary to uncoupling of
      endothelial nitric oxide synthase. Thus, nitric oxide synthase not only
      synthesizes more nitric oxide in the absence of caveolin-1, but also more
      superoxide with potential pathogenic consequences. It is further argued that the
      vasodilating drive from increased nitric oxide production in caveolin-1-deficient
      mice is balanced by changes in the vascular media that favour increased dynamic
      resistance regulation. Harnessing the therapeutic opportunities buried in
      caveolae, while challenging, could expand the arsenal of treatment options in
      cancer, lung disease and atherosclerosis.

PMID- 18826503
TI  - Re: Letter to the editor from Charissa Smith, Aust Vet J 2008;86:293.

PMID- 18826504
TI  - Permethrin intoxication.

PMID- 18826505
TI  - Re: Charissa Smith's addendum to DR Wilson's letter Aust Vet J 2008;86:293.

PMID- 18826506
TI  - Re: Letter from Charissa Smith, Aust Vet J 2008;86:293.

PMID- 18826507
TI  - Asymmetrical focal neurological deficits in dogs and cats with naturally
      occurring tick paralysis (Ixodes holocyclus): 27 cases (1999-2006).
AB  - OBJECTIVE: To describe basic epidemiological features, clinical characteristics
      and outcomes of asymmetrical focal neurological deficits identified in dogs and
      cats with naturally occurring tick paralysis (Ixodes holocyclus). DESIGN: A
      retrospective study. PROCEDURE: Computer records were reviewed for all dogs and
      cats treated for tick paralysis between July 1999 and June 2006 at a suburban
      veterinary hospital in Newcastle, New South Wales. RESULTS: Neurological deficits
      were identified in 17/197 dogs and 10/89 cats and included unilateral facial
      paralysis (14 dogs; 2 cats), anisocoria (4 dogs; 7 cats), unilateral loss of the
      cutaneous trunci reflex (1 dog; 1 cat) and Horner's syndrome in 2 cats with
      anisocoria. Occurrence of deficits was not linked to season, severity of tick
      paralysis, breed, age, sex or body weight. With facial paralysis and anisocoria,
      the site of tick attachment was invariably on the head or neck and always
      ipsilateral to the facial paralysis. By contrast, with anisocoria alone, no
      consistent relationship was noted between any one pupillary dimension and the
      side of tick attachment. With cutaneous trunci deficits the site of tick
      attachment was the ipsilateral caudal axilla. Compared with recovery times from
      generalised signs of tick paralysis, those for facial paralysis were
      significantly longer (days to weeks; P < 0.001), those for anisocoria showed no
      significant difference (P = 0.25) and those for cutaneous trunci deficits lagged
      by 6 and 7 days. CONCLUSIONS: Asymmetrical focal neurological deficits are a
      consistent finding in a proportion of dogs and cats with naturally occurring tick
      paralysis due to I. holocylcus.

PMID- 18826508
TI  - Molecular subtyping of feline immunodeficiency virus from cats in Melbourne.
AB  - OBJECTIVE: To determine the subtypes of feline immunodeficiency virus (FIV)
      present in the domestic cat population in Melbourne. METHODS: Blood samples were
      collected from 42 cats that had serum antibodies against FIV. DNA was extracted
      and subjected to polymerase chain reaction (PCR) to amplify variable regions of
      the envelope (env) and group specific antigen (gag) genes of FIV. PCR products
      were directly sequenced or sequenced after cloning when direct sequencing yielded
      ambiguous results. Phylogenetic analysis was performed and comparisons made with
      representative sequences of different subtypes. RESULTS: The variable region of
      the env gene was successfully amplified by PCR from 41 of the 42 cats. All 41
      were found to cluster with subtype A env sequences. The variable region of the
      gag gene was successfully amplified by PCR from all 42 cats. Forty-one were found
      to cluster with subtype A gag genes and one was found to cluster with subtype B
      sequences, suggesting that it may be derived from a recombinant env A/gag B
      virus. CONCLUSIONS: Subtype A is the predominant FIV type in Melbourne, although
      a subtype A/B recombinant was identified in the population of FIV positive cats.
      These results of env gene analysis were similar to those in a previous Australian
      study, suggesting that subtype A predominates in Australia. The results of the
      gag gene analysis show the importance of analysing multiple areas of the FIV
      genome when assigning FIV subtypes. Comparison with other major urban centres may
      provide useful information about the phylogenic diversity of FIV in Australia.

PMID- 18826510
TI  - Cardiac troponin I is elevated in dogs and cats with azotaemia renal failure and
      in dogs with non-cardiac systemic disease.
AB  - OBJECTIVE: To determine if dogs and cats with renal failure, or other severe non
      cardiac disease, and no antemortem evidence of cardiac disease on basic clinical
      evaluation, have elevated levels of cardiac troponin I (cTnI). DESIGN: Cross
      sectional study using 56 dogs and 14 cats with primary non-cardiac disease (39
      dogs with azotaemic renal failure, 14 cats with azotaemic renal failure, 17 dogs
      with non-cardiac systemic disease); 7/25 dogs and 6/14 cats had murmurs detected
      on physical examination. Serum or heparinised plasma was collected and analysed
      for cTnI. RESULTS: Cardiac troponin I concentrations were elevated above
      reference intervals in 70% of dogs and 70% of cats with azotaemic renal failure
      and in 70% of dogs with a variety of systemic non-cardiac diseases. Cardiac
      troponin I concentrations did not correlate with the degree of azotaemia,
      presence of murmurs, hypertension or type of non-cardiac illness. CONCLUSIONS:
      Cardiac troponin I concentration is often elevated in dogs and cats with
      azotaemic renal failure and in dogs with other systemic non-cardiac illness,
      suggesting that these conditions often result in clinically inapparent myocardial
      injury or possibly altered elimination of cTnI.

PMID- 18826511
TI  - Use of continuous positive airway pressure in the acute management of laryngeal
      paralysis in a cat.
AB  - Continuous positive airway pressure (CPAP) has been is used widely in humans to
      manage obstructive sleep apnoea syndrome, but it has not been widely used in
      animals. A brachycephalic cat, with previously undiagnosed laryngeal paralysis,
      that developed acute upper respiratory tract obstruction on recovery from
      anaesthesia, is presented. The condition was managed by CPAP, delivered via a
      facial mask.

PMID- 18826512
TI  - Financial modelling of the potential cost of ovine Johne's disease and the
      benefit of vaccinating sheep flocks in southern New South Wales.
AB  - OBJECTIVE: To develop an enterprise gross margin (GM) model that predicts the on
      farm financial impact of ovine Johne's disease (OJD) for various sheep
      enterprises in Australia. In addition, to estimate the benefits and costs of
      control through the use of the Gudair vaccination, including a breakeven point.
      DESIGN AND POPULATION: Data for the model was gained from an observational study
      conducted over a 3-year period from 2002 to 2004 using sheep from 12 OJD-infected
      flocks from southern New South Wales. Flocks ranged between 3500 and 20,000
      sheep, with owner estimates of 5% or greater OJD mortality at the start of the
      study. PROCEDURE: A GM model was developed to predict the on-farm financial
      impact of OJD for various sheep enterprises in Australia, comparing non-infected,
      infected (status quo) and infected (vaccination) disease scenarios. RESULTS:
      Vaccination breakeven points are achieved within 2 to 3 years for breeding
      enterprises if OJD mortalities are high, rising towards 7 years for a Merino ewe
      enterprise if OJD mortalities are low. CONCLUSION: The GM model demonstrates the
      returns to investment of vaccination for Australian sheep producers with OJD
      infected flocks.

PMID- 18826513
TI  - Surgical management of sand colic impactions in horses: a retrospective study of
      41 cases.
AB  - OBJECTIVE: A retrospective review of the medical records of 41 horses requiring
      abdominal surgery for sand colic. RESULTS: The diagnosis of sand colic was made
      when sand was found to be the cause of impaction of the gastrointestinal tract
      during surgical exploration. The most common clinical signs at presentation were
      abdominal pain, abdominal distension and diarrhoea. A statistically significant
      association was found between the respiratory rate on arrival and short-term
      survival. Sand impaction at multiple locations was detected in one-third of the
      horses. Concurrent pathology was detected in half of the horses. Four horses were
      euthanased during surgery; of those that recovered from surgery, 35/37 (95%) were
      discharged from hospital. Short- and long-term complications were similar to
      those previously reported. Long-term (1 year) survival of the horses discharged
      was 100%. CONCLUSION: The good prognosis for horses undergoing surgery for the
      treatment of sand impaction supports early surgical intervention in cases where
      large amounts of sand are suspected.

PMID- 18826514
TI  - Mitogen-induced responses in lymphocytes from platypus, the Tasmanian devil and
      the eastern barred bandicoot.
AB  - OBJECTIVE: As the platypus (Ornithorhynchus anatinus), the Tasmanian devil
      (Sarcophilus harrisi) and the eastern barred bandicoot (Perameles gunni) are
      currently at risk of serious population decline or extinction from fatal diseases
      in Tasmania, the goal of the present study was to describe the normal immune
      response of these species to challenge using the lymphocyte proliferation assay,
      to give a solid basis for further studies. METHODS: For this preliminary study,
      we performed lymphocyte proliferation assays on peripheral blood mononuclear
      cells (PBMC) from the three species. We used the common mitogens
      phytohaemagglutinin (PHA), concanavalin A (ConA), lipopolysaccharide (LPS) and
      pokeweed mitogen (PWM). RESULTS: All three species recorded the highest
      stimulation index (SI) with the T-cell mitogens PHA and ConA. Tasmanian devils
      and bandicoots had greater responses than platypuses, although variability
      between individual animals was high. CONCLUSION: For the first time, we report
      the normal cellular response of the platypus, the Tasmanian devil and the eastern
      barred bandicoot to a range of commonly used mitogens.

PMID- 18826516
TI  - Abstracts of the 2008 European Association for Vision and Eye Research
      Conference. October 1-4, 2008. Protoroz, Slovenia.

PMID- 18826517
TI  - Melanoma associated spongiform scleropathy: characterization, biochemical and
      immunohistochemical studies.
AB  - SUMMARY: Melanoma associated spongiform scleropathy (MASS) is a non-inflammatory
      scleral change with a spongiotic morphology seen in association with uveal
      melanoma. MASS is seen as whitish spindle shaped areas within the sclera that is
      adjacent to and in contact with a choroidal or ciliary body melanoma. This change
      can be seen as small scattered lesions in the inner scleral layers or as
      extensive areas along the whole extent of contact between the tumour and the
      sclera and involves most of the scleral thickness. MASS changes of different
      grades of severity were seen in 38% of 363 melanoma eyes investigated. The
      presence of MASS showed a statistical correlation with age. A significant high
      incidence of MASS was found in old age groups. This might due to the fact that
      MASS needs a longer period of contact between the tumour and the sclera to
      develop. It is also possible that age-related changes of the extracellular matrix
      might alter its response to melanoma produced factors leading to the development
      of MASS. The development of MASS and its severity are influenced by the extent of
      contact between the tumour and the sclera. This is supported by the significant
      statistical relation between the largest basal diameter of the tumours and the
      severity of MASS. Statistical correlation was found between MASS and scleral and
      extrascleral tumour extension. More than 90% of 82 specimens that showed tumour
      extension were associated with MASS. A biochemical analysis of scleral samples
      taken from areas with severe MASS showed a significant reduction of the main
      amino acids of collagen type I, which is the main scleral collagen. The amounts
      of total scleral proteins were significantly reduced. This scleral protein
      reduction is associated with an increase in glycosaminoglycans. These findings
      indicate a collagen degradation process. Immunohistochemical studies were
      performed to investigate the expression of matrix metalloproteinases (MMPs). In
      situ hybridization showed a significantly more frequent and more intense
      expression of MMP-2 by scleral fibroblasts in areas with MASS compared with areas
      without MASS. This was also seen by immunohistochemical staining. Similar high
      frequency and intense expression of MMP-2 were seen in tumour infiltrating
      macrophages. The results of biochemical and immunohistochemical studies indicate
      a collagen degradation process. This degradation may be the result of the
      proteolytic enzyme MMP-2 expressed by scleral fibroblasts under the effect of
      tumour humeral factors and/or tumour infiltrating macrophages. This scleral
      degradation results in fragmentation of the scleral collagen fibrils. This along
      with the accumulation of water in the sclera, as a result of the increase in the
      production of glycosaminoglycans, results in increase of scleral thickness in
      MASS areas and forms the histopathological picture of MASS. The scleral
      degradation may facilitate tumour invasion and may explain the statistical
      relation between MASS and scleral tumour invasion. MASS was found in a few of the
      eyes that had received pre-enucleation radiation. The possible explanation is
      that radiation might cause destruction of scleral fibroblasts reducing their
      ability to produce MMP-2, thus decreasing the development of MASS. No relation
      between MASS and survival was found. This is probably explained by the fact that
      the main cause of death due to uveal melanoma is distant metastasis. MASS changes
      are found to be associated with local tumour invasion but not statistically
      correlated to survival.

PMID- 18826518
TI  - Prediction and reverse prediction in therapeutics and toxicology.

PMID- 18826519
TI  - Choice of first antihypertensive - are existing guidelines ignored? Response to
      Vegter & de Jong-van den Berg.

PMID- 18826521
TI  - Direct and indirect aggression during childhood and adolescence: a meta-analytic
      review of gender differences, intercorrelations, and relations to maladjustment.
AB  - This meta-analytic review of 148 studies on child and adolescent direct and
      indirect aggression examined the magnitude of gender differences,
      intercorrelations between forms, and associations with maladjustment. Results
      confirmed prior findings of gender differences (favoring boys) in direct
      aggression and trivial gender differences in indirect aggression. Results also
      indicated a substantial intercorrelation (r = .76) between these forms. Despite
      this high intercorrelation, the 2 forms showed unique associations with
      maladjustment: Direct aggression is more strongly related to externalizing
      problems, poor peer relations, and low prosocial behavior, and indirect
      aggression is related to internalizing problems and higher prosocial behavior.
      Moderation of these effect sizes by method of assessment, age, gender, and
      several additional variables were systematically investigated.

PMID- 18826522
TI  - Development of three-dimensional object completion in infancy.
AB  - Three-dimensional (3D) object completion was investigated by habituating 4- and 6
      month-old infants (n= 24 total) with a computer-generated wedge stimulus that
      pivoted 15 degrees , providing only a limited view. Two displays, rotating 360
      degrees , were then shown: a complete, solid volume and an incomplete, hollow
      form composed only of the sides seen during habituation. There were no reliable
      preferences for either test display by 4-month-olds. At 6 months, infants showed
      a reliable novelty preference for the incomplete test display. Infants in a
      control group (n= 24) not habituated to the limited-view wedge preferred neither
      test display. By 6 months, infants may represent simple objects as complete in 3D
      space despite a limited perspective. Possible mechanisms of development of 3D
      object completion are discussed.

PMID- 18826523
TI  - Young children's recognition of the intentionality of teaching.
AB  - Two studies examined the role of intention in preschoolers' understanding of
      teaching. Three- to 5-year-olds judged stories in which there was an intention to
      teach or not (teaching vs. imitation) for 4 different learning outcomes
      (successful, partial, failed, and unknown). They also judged 2 stories with
      embedded instructional intent (e.g., guided discovery learning) and several
      standard theory of mind tasks. There was an age-related change in the
      understanding of teaching. Five-year-olds distinguished teaching from imitation
      and recognized guided discovery learning. Understanding of imitation and false
      belief was related. The findings indicate that theory of mind is relevant to
      other means of knowledge acquisition besides perceptual access and that
      understanding intention could help young children to recognize instruction and
      identify its different forms.

PMID- 18826524
TI  - Changes in the relation of self-efficacy beliefs and behaviors across
      development.
AB  - Many social science theories that examine the connection between beliefs and
      behaviors assume that belief constructs will predict behaviors similarly across
      development. Converging research implies that this assumption may not be tenable
      across all ages or all belief constructs. Thus, to test this implication, the
      relation between behavior and beliefs about the self was examined in 2
      independent data sets with 2 different constructs: aggression and achievement.
      The respondents were 6-18 years of age and predominately Caucasian. Results using
      quasi-simplex structural equation models suggest that self-beliefs become more
      strongly related to behavior as children grow older independent of the
      reliability of the measures used. Possible limitations in the use of self-report
      methodology with young children are discussed.

PMID- 18826525
TI  - Categories influence predictions about individual consistency.
AB  - Predicting how people will behave in the future is a critical social-cognitive
      task. In four studies (N = 150, ages preschool to adult), young children (ages 4
      5) used category information to guide their expectations about individual
      consistency. They predicted that psychological properties (preferences and fears)
      would remain consistent over time after hearing one example in which properties
      followed a category-linked distribution (e.g., children of different genders had
      different properties) but not when properties varied within a category (e.g.,
      children of the same gender had different properties). The developmental course
      of these findings is examined. Results suggest the importance of considering how
      children's emerging theories of behavior and of social groups operate together to
      inform their expectations about the social world.

PMID- 18826526
TI  - Stability and change of moral disengagement and its impact on aggression and
      violence in late adolescence.
AB  - Stability and change of moral disengagement were examined in a sample of 366
      adolescents from ages 14 to 20 years. Four developmental trajectories were
      identified: (a) nondisengaged group that started with initially low levels
      followed by an important decline, (b) normative group that started with initially
      moderate levels followed by a decline, (c) later desister group that started with
      initially high-medium levels followed by an increase from 14 to 16 years and an
      even steeper decline from 16 to 20 years, and (d) chronic group that started with
      and maintained medium-high levels. The results attest that adolescents who
      maintained higher levels of moral disengagement were more likely to show frequent
      aggressive and violent acts in late adolescence.

PMID- 18826527
TI  - Arguing on the computer: a microgenetic study of developing argument skills in a
      computer-supported environment.
AB  - We report a study of a class of 28 sixth graders engaged in an extended computer
      supported argumentive discourse activity. Participants collaborated with a same
      side peer in arguing against successive pairs of peers on the opposing side of an
      issue. Meta-level awareness was facilitated by conducting the dialogs via instant
      messaging software, which made available a transcript of the dialog that was used
      in additional reflective activities. In the course of dialogs on 3 successive
      topics, participants showed significant gains in meta-level communications about
      the discourse, reflecting at least implicit understanding of its goals, as well
      as in the strategic moves that constituted the discourse. The latter advances
      remained evident when the social support of a same-side partner was withdrawn.

PMID- 18826528
TI  - The influence of race and gender on children's conversations and playmate
      choices.
AB  - The present study examined the influence of race and gender on children's
      conversations and friendship choices. Four hundred and twenty-eight children (M
      age = 7.5 years, SD = 0.34) from 2 racial minority groups (i.e., African
      Caribbean and South Asian) and the racial majority group (i.e., European) chose a
      picture of a playmate together with a peer. Race influenced the levels of
      assertion and affiliation in children's conversations. The effects of race on
      conversation also varied according to the gender of the children involved in
      interaction. Same-race pairs tended to choose in-group playmates, but same-race
      minority pairs showed less marked in-group preference. Cross-race pairs selected
      a majority-group child as a playmate most often.

PMID- 18826529
TI  - Where is the essence? Developmental shifts in children's beliefs about internal
      features.
AB  - The present studies investigated children's and adults' intuitive beliefs about
      the physical nature of essences. Adults and children (ranging in age from 6 to 10
      years old) were asked to reason about 2 different ways of determining an unknown
      object's category: taking a tiny internal sample from any part of the object
      (distributed view of essence) or taking a sample from one specific region
      (localized view of essence). Results from 3 studies indicated that adults
      strongly endorsed the distributed view, and children showed a developmental shift
      from a localized to distributed view with increasing age. These results suggest
      that even children go beyond mere placeholder notions of essence, committing to
      conceptual frameworks of how essences might be physically instantiated.

PMID- 18826530
TI  - Profiles of disruptive behavior across early childhood: contributions of
      frustration reactivity, physiological regulation, and maternal behavior.
AB  - Disruptive behavior, including aggression, defiance, and temper tantrums,
      typically peaks in early toddlerhood and decreases by school entry; however, some
      children do not show this normative decline. The current study examined
      disruptive behavior in 318 boys and girls at 2, 4, and 5 years of age and
      frustration reactivity, physiological regulation, and maternal behavior in the
      laboratory at 2 years of age. A latent profile analysis resulted in 4
      longitudinal profiles of disruptive behavior, which were differentiated by
      interactions between reactivity, regulation, and maternal behavior. A high
      profile was associated with high reactivity combined with high maternal control
      or low regulation combined with low maternal control. Results are discussed from
      a developmental psychopathology perspective.

PMID- 18826531
TI  - Gene-environment contributions to the development of infant vagal reactivity: the
      interaction of dopamine and maternal sensitivity.
AB  - This study investigated dopamine receptor genes (DRD2 and DRD4) and maternal
      sensitivity as predictors of infant respiratory sinus arrhythmia (RSA) and RSA
      reactivity, purported indices of vagal tone and vagal regulation, in a challenge
      task at 3, 6, and 12 months in 173 infant-mother dyads. Hierarchical linear
      modeling (HLM) revealed that at 3 and 6 months, RSA withdrawal in response to
      maternal separation was greater (suggesting expected physiological regulation) in
      infants without the DRD2 risk allele than those with the risk allele. At 12
      months, infants with the risk allele who were also exposed to maternal
      sensitivity showed levels of RSA withdrawal comparable to infants who were not at
      genetic risk. Findings demonstrate the importance of developmental analysis of
      gene-environment interaction.

PMID- 18826532
TI  - The family check-up with high-risk indigent families: preventing problem behavior
      by increasing parents' positive behavior support in early childhood.
AB  - Seven hundred thirty-one income-eligible families in 3 geographical regions who
      were enrolled in a national food supplement program were screened and randomized
      to a brief family intervention. At child ages 2 and 3, the intervention group
      caregivers were offered the Family Check-Up and linked parenting support
      services. Latent growth models on caregiver reports at child ages 2, 3, and 4
      revealed decreased behavior problems when compared with the control group.
      Intervention effects occurred predominantly among families reporting high levels
      of problem behavior at child age 2. Families in the intervention condition
      improved on direct observation measures of caregivers' positive behavior support
      at child ages 2 and 3; improvements in positive behavior support mediated
      improvements in children's early problem behavior.

PMID- 18826533
TI  - Maternal socialization of positive affect: the impact of invalidation on
      adolescent emotion regulation and depressive symptomatology.
AB  - This study examined the relations among maternal socialization of positive affect
      (PA), adolescent emotion regulation (ER), and adolescent depressive symptoms. Two
      hundred early adolescents, 11-13 years old, provided self-reports of ER
      strategies and depressive symptomatology; their mothers provided self-reports of
      socialization responses to adolescent PA. One hundred and sixty-three mother
      adolescent dyads participated in 2 interaction tasks. Adolescents whose mothers
      responded in an invalidating or "dampening" manner toward their PA displayed more
      emotionally dysregulated behaviors and reported using maladaptive ER strategies
      more frequently. Adolescents whose mothers dampened their PA more frequently
      during mother-adolescent interactions, and girls whose mothers reported
      invalidating their PA, reported more depressive symptoms. Adolescent use of
      maladaptive ER strategies mediated the association between maternal invalidation
      of PA and early adolescents' concurrent depressive symptoms.

PMID- 18826534
TI  - Infants' use of lexical-category-to-meaning links in object individuation.
AB  - Infants watched an experimenter retrieve a stuffed animal from an opaque box and
      then return it. This happened twice, consistent with either 1 animal appearing on
      2 occasions or 2 identical-looking animals each appearing once. The experimenter
      labeled each object appearance with a different novel label. After infants
      retrieved 1 object from the box, their subsequent search behavior was recorded.
      Twenty-month-olds, but not 16-month-olds, searched significantly longer for a
      second object inside the box when the labels were both proper names than when
      they were 1 count noun followed by 1 proper name. The effect was not significant
      when proper names were replaced by adjectives. Twenty-month-olds' understanding
      of meaning distinctions among several word categories guided their object
      individuation.

PMID- 18826535
TI  - Development of emotional and behavioral regulation in children born extremely
      preterm and very preterm: biological and social influences.
AB  - This study describes the development of emotional and behavioral regulation in a
      regional cohort of children born extremely preterm (<28 weeks gestational age, n
      = 39), very preterm (<34 weeks gestational age, n = 56), and full term (n = 103).
      At 2 and 4 years, children born at younger gestational ages demonstrated poorer
      self-regulation across multiple contexts spanning observed interactions, formal
      cognitive testing, and parental report of child behavior at home. Among children
      born preterm, the 2 strongest predictors of impairments in self-regulation were
      the presence of moderate-to-severe cerebral white matter abnormalities on
      neonatal magnetic resonance and a less sensitive parenting style when children
      were aged 2 years. Findings support the importance of early neurological
      development and parenting for developing regulation in children born very
      preterm.

PMID- 18826536
TI  - Neighborhood poverty and early transition to sexual activity in young
      adolescents: a developmental ecological approach.
AB  - This study examined how the link between neighborhood poverty and the timing of
      sexual initiation varies as a function of age, gender, and background
      characteristics. A sample of N = 2,596 predominately White Canadian adolescents
      from the National Longitudinal Survey of Children and Youth was used. Sexual
      initiations occurring between 12 and 15 years old were considered. Results showed
      that younger adolescent females who lived in poor neighborhoods and who had a
      history of conduct problems were more likely to report early sexual activity.
      Peer characteristics partly accounted for this susceptibility. Among adolescent
      males, no direct neighborhood effects were found, but those who had combined
      risks at multiple levels appeared more vulnerable. The theoretical and practical
      implications of these findings are discussed.

PMID- 18826537
TI  - Searching and planning: young children's reasoning about past and future event
      sequences.
AB  - Six experiments examined children's ability to make inferences using temporal
      order information. Children completed versions of a task involving a toy zoo; one
      version required reasoning about past events (search task) and the other required
      reasoning about future events (planning task). Children younger than 5 years
      failed both the search and the planning tasks, whereas 5-year-olds passed both
      (Experiments 1 and 2). However, when the number of events in the sequence was
      reduced (Experiment 3), 4-year-olds were successful on the search task but not
      the planning task. Planning difficulties persisted even when relevant cues were
      provided (Experiments 4 and 5). Experiment 6 showed that improved performance on
      the search task found in Experiment 3 was not due to the removal of response
      ambiguity.

PMID- 18826539
TI  - Limitations in 4-year-old children's sensitivity to the spacing among facial
      features.
AB  - Four-year-olds' sensitivity to differences among faces in the spacing of features
      was tested under 4 task conditions: judging distinctiveness when the external
      contour was visible and when it was occluded, simultaneous match-to-sample, and
      recognizing the face of a friend. In each task, the foil differed only in the
      spacing of features, and spacing alterations were within normal limits. Children
      performed at chance levels in all but 1 task-match-to-sample, and in that task,
      only 10 of 18 children were correct on more than 50% of the trials. Sensitivity
      to the spacing of facial features in identity and distinctiveness tasks is very
      weak at 4 years of age-at least when the changes do not exceed +/-2.5 SD of
      normal variability.

PMID- 18826538
TI  - Effects of family violence on psychopathology symptoms in children previously
      exposed to maltreatment.
AB  - Although many studies suggest that family violence is associated with child
      psychopathology, multiple features of the home environment might account for this
      association, such as poverty and caregiver psychopathology. Studies are needed
      examining how change in psychopathology symptoms is affected by home violence,
      controlling for children's own developmental symptom histories and other
      predictors of psychopathology. This study used latent difference score structural
      equation modeling to test if witnessing home violence and/or experiencing harsh
      physical discipline predicted changes in psychopathology symptoms among 2,925
      youth aged 5-16 years previously exposed to violence. Results demonstrated that
      harsh physical discipline predicted child-specific changes in externalizing
      symptoms, whereas witnessing violence predicted child-specific changes in
      internalizing symptoms across time. Implications for research and policy are
      discussed.

PMID- 18826540
TI  - Limitations to teaching children 2 + 2 = 4: typical arithmetic problems can
      hinder learning of mathematical equivalence.
AB  - Do typical arithmetic problems hinder learning of mathematical equivalence?
      Second and third graders (7-9 years old; N= 80) received lessons on mathematical
      equivalence either with or without typical arithmetic problems (e.g., 15 + 13 =
      28 vs. 28 = 28, respectively). Children then solved math equivalence problems
      (e.g., 3 + 9 + 5 = 6 + _), switched lesson conditions, and solved math
      equivalence problems again. Correct solutions were less common following
      instruction with typical arithmetic problems. In a supplemental experiment, fifth
      graders (10-11 years old; N= 19) gave fewer correct solutions after a brief
      intervention on mathematical equivalence that included typical arithmetic
      problems. Results suggest that learning is hindered when lessons activate
      inappropriate existing knowledge.

PMID- 18826541
TI  - Perception of dynamic and static audiovisual sequences in 3- and 4-month-old
      infants.
AB  - This study investigated perception of audiovisual sequences in 3- and 4-month-old
      infants. Infants were habituated to sequences consisting of moving/sounding or
      looming/sounding objects and then tested for their ability to detect changes in
      the order of the objects, sounds, or both. Results showed that 3-month-olds
      perceived the order of 3-element sequences and that 4-month-olds perceived the
      order of 3- and 4-element sequences. In addition, results indicated that
      perception of moving sequences was more robust than of looming ones and that
      detection of order differences was not based on primacy cues. The current results
      show that perception of multisensory sequences and their structure emerges early
      in development, and a preliminary model of the development of sequence perception
      is offered.

PMID- 18826542
TI  - Longitudinal analysis of intrinsic motivation and competence beliefs: is there a
      relation over time?
AB  - The present study explored whether competence beliefs and intrinsic motivation
      for different school domains show reciprocal effects over time. A sample of 670
      German elementary school pupils (M= 8.8 years, SD= 0.51) was followed over 1
      year. At 4 measurement occasions, children completed self-reports on their
      intrinsic motivation and competence beliefs for math, German, and school in
      general. Latent growth models revealed that intrinsic motivation and competence
      beliefs decreased over time. Comparing correlational and cross-lagged structural
      equation models yielded only weak evidence for cross-lagged influences between
      the 2 constructs. Results suggest that the developmental curves of competence
      beliefs and intrinsic motivation might be less inextricably interwoven than
      frequently assumed.

PMID- 18826543
TI  - Children's insecure representations of the interparental relationship and their
      school adjustment: the mediating role of attention difficulties.
AB  - This study examined the role of attention difficulties as a mediator of
      associations between children's insecure representations of the interparental
      relationship and their school adjustment in a sample of two hundred and sixteen 6
      year-old children. Consistent with hypotheses, findings from structural equation
      models indicated that observer ratings of children's insecure representations of
      interparental relationships in a story completion task predicted computerized
      task assessments and parent reports of children's attention difficulties 1 year
      later. Children's attention difficulties, in turn, were associated with
      concurrent levels of school problems and increases in school problems over a 1
      year period as indexed by teacher reports. Attention difficulties accounted for
      an average of 34% of the association between insecure internal representations
      and school problems.

PMID- 18826544
TI  - Developmental trajectories of sex-typed behavior in boys and girls: a
      longitudinal general population study of children aged 2.5-8 years.
AB  - The stability of sex-typed behavior from the preschool to the middle school years
      was examined. The Preschool Activities Inventory, a measure of within-sex
      variation in sex-typed behavior, was completed by the primary caregiver when the
      child was 2.5, 3.5, and 5 years, and a modified version, the Child Activities
      Inventory, was completed by the child at age 8. The investigation involved a
      general population sample of 2,726 boys and 2,775 girls. Sex-typed behavior
      increased through the preschool years, and those children who were the most sex
      typed at age 2.5 were still the most sex typed at age 5, with those children who
      showed the highest levels of sex-typed behavior during the preschool years
      continuing to do so at age 8.

PMID- 18826545
TI  - Microbial community networks.

PMID- 18826546
TI  - British HIV Association Guidelines for the treatment of HIV-1-infected adults
      with antiretroviral therapy 2008.

PMID- 18826550
TI  - Abstracts of the Australian & New Zealand Society for Geriatric Medicine Annual
      Scientific Meeting. September, 8-10, 2008. Melbourne, Australia.

PMID- 18826552
TI  - The evolution of multiple forms of cutaneous lupus erythematosus in the same
      patient over time.

PMID- 18826554
TI  - Abstracts of the RANZCR 59th Annual Scientific Meeting. October 16-19, 2008.
      Adelaide, Australia.

PMID- 18826556
TI  - Abstracts of the Royal Australian and New Zealand College of Radiologists
      (RANZCR) 59th Annual Scientific Meeting. October 16-19, 2008. Adelaide,
      Australia.

PMID- 18826558
TI  - Anti-flagellin antibodies in irritable bowel syndrome: another attack on our
      commensals?

PMID- 18826559
TI  - Design of treatment trials in irritable bowel syndrome: opioid agonists and
      atypical benzodiazepine antagonists.
AB  - Irritable bowel syndrome (IBS) is a common gastrointestinal disorder
      characterized by abdominal pain and altered bowel function. Few agents are
      available for the treatment of IBS. Historically, one impediment to the
      development of agents to treat IBS was lack of a uniform and robust clinical
      trial design. Studies occurred with different durations of treatment, endpoints
      and with different target populations. Great advances have been made over the
      past decade in trial design including: optimal duration of study, mode of data
      collection, populations to evaluate and identification of endpoints. Using these
      refinements, it was possible to demonstrate the efficacy of some new agents.
      These advances are illustrated by a review of trials with kappa opioid agonists
      and atypical benzodiazepine antagonists, which appear to be promising new classes
      of treatments for symptoms in IBS.

PMID- 18826560
TI  - The endomembrane system: a green perspective.

PMID- 18826561
TI  - Assessing the unintended health impacts of road transport policies and
      interventions: translating research evidence for use in policy and practice.
AB  - BACKGROUND: Transport and its links to health and health inequalities suggest
      that it is important to assess both the direct and unintended indirect health and
      related impacts of transport initiatives and policies. Health Impact Assessment
      (HIA) provides a framework to assess the possible health impacts of interventions
      such as transport. Policymakers and practitioners need access to well conducted
      research syntheses if research evidence is to be used to inform these
      assessments. The predictive validity of HIA depends heavily on the use and
      careful interpretation of supporting empirical evidence. Reviewing and digesting
      the vast volume and diversity of evidence in a field such as transport is likely
      to be beyond the scope of most HIAs. Collaborations between HIA practitioners and
      specialist reviewers to develop syntheses of best available evidence applied
      specifically to HIA could promote the use of evidence in practice. METHODS: Best
      available research evidence was synthesised using the principles of systematic
      review. The synthesis was developed to reflect the needs of HIA practitioners and
      policymakers. RESULTS: Aside from injury reduction measures, there is very little
      empirical data on the impact of road transport interventions. The possibility of
      impacts on a diverse range of outcomes and differential impacts across groups,
      make it difficult to assess overall benefit and harm. In addition, multiple
      mediating factors in the pathways between transport and hypothesised health
      impacts further complicate prospective assessment of impacts. Informed by the
      synthesis, a framework of questions was developed to help HIA practitioners
      identify the key questions which need to be considered in transport HIA.
      CONCLUSION: Principles of systematic review are valuable in producing syntheses
      of best available evidence for use in HIA practice. Assessment of the health
      impacts of transport interventions is characterised by much uncertainty,
      competing values, and differential or conflicting impacts for different
      population groups at a local or wider level. These are issues pertinent to the
      value of HIA generally. While uncertainty needs explicit acknowledgement in HIA,
      there is still scope for best available evidence to inform the development of
      healthy public policy.

PMID- 18826562
TI  - Socio-economic status and overall and cause-specific mortality in Sweden.
AB  - BACKGROUND: Previous studies have reported discrepancies in cause-specific
      mortality among groups of individuals with different socio-economic status.
      However, most of the studies were limited by the specificity of the investigated
      populations and the broad definitions of the causes of death. The aim of the
      present population-based study was to explore the dependence of disease specific
      mortalities on the socio-economic status in Sweden, a country with universal
      health care. Another aim was to investigate possible gender differences. METHODS:
      Using the 2006 update of the Swedish Family-Cancer Database, we identified over 2
      million individuals with socio-economic data recorded in the 1960 national
      census. The association between mortality and socio-economic status was
      investigated by Cox's proportional hazards models taking into account the age,
      time period and residential area in both men and women, and additionally parity
      and age at first birth in women. RESULTS: We observed significant associations
      between socio-economic status and mortality due to cardiovascular diseases,
      respiratory diseases, to cancer and to endocrine, nutritional and metabolic
      diseases. The influence of socio-economic status on female breast cancer was
      markedly specific: women with a higher socio-economic status showed increased
      mortality due to breast cancer. CONCLUSION: Even in Sweden, a country where
      health care is universally provided, higher socio-economic status is associated
      with decreased overall and cause-specific mortalities. Comparison of mortality
      among female and male socio-economic groups may provide valuable insights into
      the underlying causes of socio-economic inequalities in length of life.

PMID- 18826563
TI  - Idiopathic Brainstem Neuronal Chromatolysis (IBNC): a novel prion protein related
      disorder of cattle?
AB  - BACKGROUND: The epidemic form of Bovine Spongiform Encephalopathy (BSE) is
      generally considered to have been caused by a single prion strain but at least
      two strain variants of cattle prion disorders have recently been recognized. An
      additional neurodegenerative condition, idiopathic brainstem neuronal
      chromatolysis and hippocampal sclerosis (IBNC), a rare neurological disease of
      adult cattle, was also recognised in a sub-set of cattle submitted under the BSE
      Orders in which lesions of BSE were absent. Between the years of 1988 and 1991
      IBNC occurred in Scotland with an incidence of 7 cases per 100,000 beef suckler
      cows over the age of 6 years. RESULTS: When the brains of 15 IBNC cases were each
      tested by immunohistochemistry, all showed abnormal labelling for prion protein
      (PrP). Immunohistological labelling for PrP was also present in the retina of a
      single case available for examination. The pattern of PrP labelling in brain is
      distinct from that seen in other ruminant prion diseases and is absent from
      brains with other inflammatory conditions and from normal control brains. Brains
      of IBNC cattle do not reveal abnormal PrP isoforms when tested by the commercial
      BioRad or Idexx test kits and do not reveal PrPres when tested by Western
      blotting using stringent proteinase digestion methods. However, some weakly
      protease resistant isoforms of PrP may be detected when tissues are examined
      using mild proteinase digestion techniques. CONCLUSION: The study shows that a
      distinctive neurological disorder of cattle, which has some clinical similarities
      to BSE, is associated with abnormal PrP labelling in brain but the pathology and
      biochemistry of IBNC are distinct from BSE. The study is important either because
      it raises the possibility of a significant increase in the scope of prion disease
      or because it demonstrates that widespread and consistent PrP alterations may not
      be confined to prion diseases. Further studies, including transmission
      experiments, are needed to establish whether IBNC is a condition in which prion
      protein is abnormally regulated or it is yet a further example of an infectious
      cattle prion disease.

PMID- 18826564
TI  - Wnt signalling in human breast cancer: expression of the putative Wnt inhibitor
      Dickkopf-3 (DKK3) is frequently suppressed by promoter hypermethylation in
      mammary tumours.
AB  - INTRODUCTION: Expression of the putative Wnt signalling inhibitor Dickkopf-3
      (DKK3) is frequently lost in human cancer tissues because of aberrant 5'-cytosine
      methylation within the DKK3 gene promoter. Since other Wnt signalling inhibitors
      have been reported to be targets of epigenetic inactivation in human breast
      cancer, we questioned if DKK3 expression is also epigenetically silenced during
      breast carcinogenesis and therefore might contribute to oncogenic Wnt signalling
      commonly found in this disease. METHODS: DKK3 mRNA expression and DKK3 promoter
      methylation were determined by RT-PCR, realtime PCR and methylation-specific PCR
      in breast cell lines (n = 9), normal breast tissues (n = 19) and primary breast
      carcinomas (n = 150), respectively. In vitro DNA demethylation was performed by
      incubating breast cell lines with 5-aza-2'-deoxycytidine and trichostatin A. DKK3
      protein expression was analysed by immunohistochemistry in breast carcinomas (n =
      16) and normal breast tissues (n = 8). Methylation data were statistically
      correlated with clinical patient characteristics. All statistical evaluations
      were performed with SPSS 14.0 software. RESULTS: DKK3 mRNA was downregulated in
      71% (five of seven) of breast cancer cell lines and in 68% of primary breast
      carcinomas (27 of 40) compared with benign cell lines and normal breast tissues,
      respectively. A DNA demethylating treatment of breast cell lines resulted in
      strong induction of DKK3 mRNA expression. In tumourous breast tissues, DKK3 mRNA
      downregulation was significantly associated with DKK3 promoter methylation (p <
      0.001). Of the breast carcinomas, 61% (92 of 150) revealed a methylated DKK3
      promoter, whereas 39% (58 of 150) retained an unmethylated promoter. Loss of DKK3
      expression in association with DKK3 promoter methylation (p = 0.001) was also
      confirmed at the protein level (p < 0.001). In bivariate analysis, DKK3 promoter
      methylation was not associated with investigated clinicopathological parameters
      except patient age (p = 0.007). CONCLUSIONS: DKK3 mRNA expression and
      consequently DKK3 protein expression become frequently downregulated during human
      breast cancer development due to aberrant methylation of the DKK3 promoter. Since
      DKK3 is thought to negatively regulate oncogenic Wnt signalling, DKK3 may be a
      potential tumour suppressor gene in normal breast tissue.

PMID- 18826566
TI  - Citation of non-English peer review publications--some Chinese examples.
AB  - Articles published in English language journals with citations of non-English
      peer reviewed materials are not very common today. However, as epidemiologists
      are becoming more aware of data and information being readily available and
      accessible in the non-English literature, the question of whether non-English
      materials can be cited in English language journals and if so, how should they be
      cited, has become an increasingly important issue. Bringing together personal
      insights from the author's familiarity with both the English and Chinese language
      epidemiological literature and results from a survey on the use of citations of
      non-English peer reviewed materials across a sample of epidemiology and public
      health journals, this commentary discusses the different ways authors cite non
      English articles in different English language journals and the different methods
      used by journals to handle non-Latin scripts (e.g. transliteration). This
      commentary will be useful to both epidemiologists and editors alike.

PMID- 18826565
TI  - The role of antioxidant supplement in immune system, neoplastic, and
      neurodegenerative disorders: a point of view for an assessment of the
      risk/benefit profile.
AB  - This review will discuss some issues related to the risk/benefit profile of the
      use of dietary antioxidants. Thus, recent progress regarding the potential
      benefit of dietary antioxidants in the treatment of chronic diseases with a
      special focus on immune system and neurodegenerative disorders will be discussed
      here. It is well established that reactive oxygen species (ROS) play an important
      role in the etiology of numerous diseases, such as atherosclerosis, diabetes and
      cancer. Among the physiological defense system of the cell, the relevance of
      antioxidant molecules, such as glutathione and vitamins is quite well
      established. Recently, the interest of researchers has, for example, been
      conveyed on antioxidant enzyme systems, such as the heme oxygenase/biliverdin
      reductase system, which appears modulated by dietary antioxidant molecules,
      including polyphenols and beta-carotene. These systems possibly counteract
      oxidative damage very efficiently and finally modulate the activity of oxidative
      phenomena occurring, for instance, during pathophysiological processes. Although
      evidence shows that antioxidant treatment results in cytoprotection, the
      potential clinical benefit deriving from both nutritional and supplemental
      antioxidants is still under wide debate. In this line, the inappropriate
      assumption of some lipophylic vitamins has been associated with increased
      incidence of cancer rather than with beneficial effects.

PMID- 18826567
TI  - Enhancing access to reports of randomized trials published world-wide--the
      contribution of EMBASE records to the Cochrane Central Register of Controlled
      Trials (CENTRAL) in The Cochrane Library.
AB  - BACKGROUND: Randomized trials are essential in assessing the effects of
      healthcare interventions and are a key component in systematic reviews of
      effectiveness. Searching for reports of randomized trials in databases is
      problematic due to the absence of appropriate indexing terms until the 1990s and
      inconsistent application of these indexing terms thereafter. OBJECTIVES: The
      objectives of this study are to devise a search strategy for identifying reports
      of randomized trials in EMBASE which are not already indexed as trials in MEDLINE
      and to make these reports easily accessible by including them in the Cochrane
      Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, with the
      permission of Elsevier, the publishers of EMBASE. METHODS: A highly sensitive
      search strategy was designed for EMBASE based on free-text and thesaurus terms
      which occurred frequently in the titles, abstracts, EMTREE terms (or some
      combination of these) of reports of trials indexed in EMBASE. This search
      strategy was run against EMBASE from 1980 to 2005 (1974 to 2005 for four of the
      terms) and records retrieved by the search, which were not already indexed as
      randomized trials in MEDLINE, were downloaded from EMBASE, printed and read. An
      analysis of the language of publication was conducted for the reports of trials
      published in 2005 (the most recent year completed at the time of this study).
      RESULTS: Twenty-two search terms were used (including nine which were later
      rejected due to poor cumulative precision). More than a third of a million
      records were downloaded and scanned and approximately 80,000 reports of trials
      were identified which were not already indexed as randomized trials in MEDLINE.
      These are now easily identifiable in CENTRAL, in The Cochrane Library. Cumulative
      sensitivity ranged from 0.1% to 60% and cumulative precision ranged from 8% to
      61%. The truncated term 'random$' identified 60% of the total number of reports
      of trials but only 35% of the more than 130,000 records retrieved by this term
      were reports of trials. The language analysis for the sample year 2005 indicated
      that of the 18,427 reports indexed as randomized trials in MEDLINE, 959 (5%) were
      in languages other than English. The EMBASE search identified an additional 658
      reports in languages other than English, of which the highest number were in
      Chinese (320). CONCLUSION: The results of the search to date have greatly
      increased access to reports of trials in EMBASE, especially in some languages
      other than English. The search strategy used was subjectively derived from a
      small 'gold standard' set of test records and was not validated in an independent
      test set. We intend to design an objectively-derived validated search strategy
      using logistic regression based on the frequency of occurrence of terms in the
      approximately 80,000 reports of randomized trials identified compared with the
      frequency of these terms across the entire EMBASE database.

PMID- 18826568
TI  - Index Medicus for the Eastern Mediterranean region.
AB  - The study provides the rationale, history and current status of the Index Medicus
      for the World Health Organization Eastern Mediterranean Region. The Index is
      unique in combining the geographic coverage of peer-reviewed health and
      biomedical journals (408 titles) from the 22 countries of the Region. Compiling
      and publishing the Index coupled with a document delivery service is an integral
      part of the WHO Regional Office's knowledge management and sharing programme. In
      this paper, bibliometric indicators are presented to demonstrate the distribution
      of journals, articles, languages, subjects and authors as well as availability in
      printed and electronic formats. Two countries in the Region (Egypt and Pakistan)
      contribute over 50% of the articles in the Index. About 90% of the articles are
      published in English. Epidemiology articles represent 8% of the entire Index. 15%
      of the journals in the Index are also indexed in MEDLINE, while 7% are indexed in
      EMBASE. Future developments of the Index will include covering more journals and
      adding other types of health and biomedical literature, including reports,
      theses, books and current research. The challenges and lessons learnt are
      discussed.

PMID- 18826569
TI  - Biomedical journals and databases in Russia and Russian language in the former
      Soviet Union and beyond.
AB  - In the 20th century, Russian biomedical science experienced a decline from the
      blossom of the early years to a drastic state. Through the first decades of the
      USSR, it was transformed to suit the ideological requirements of a totalitarian
      state and biased directives of communist leaders. Later, depressing economic
      conditions and isolation from the international research community further
      impeded its development. Contemporary Russia has inherited a system of medical
      education quite different from the west as well as counterproductive regulations
      for the allocation of research funding. The methodology of medical and
      epidemiological research in Russia is largely outdated. Epidemiology continues to
      focus on infectious disease and results of the best studies tend to be published
      in international periodicals. MEDLINE continues to be the best database to search
      for Russian biomedical publications, despite only a small proportion being
      indexed. The database of the Moscow Central Medical Library is the largest
      national database of medical periodicals, but does not provide abstracts and full
      subject heading codes, and it does not cover even the entire collection of the
      Library. New databases and catalogs (e.g. Panteleimon) that have appeared
      recently are incomplete and do not enable effective searching.

PMID- 18826570
TI  - Does language matter? A case study of epidemiological and public health journals,
      databases and professional education in French, German and Italian.
AB  - Epidemiology and public health are usually context-specific. Journals published
      in different languages and countries play a role both as sources of data and as
      channels through which evidence is incorporated into local public health
      practice. Databases in these languages facilitate access to relevant journals,
      and professional education in these languages facilitates the growth of native
      expertise in epidemiology and public health. However, as English has become the
      lingua franca of scientific communication in the era of globalisation, many
      journals published in non-English languages face the difficult dilemma of either
      switching to English and competing internationally, or sticking to the native
      tongue and having a restricted circulation among a local readership. This paper
      discusses the historical development of epidemiology and the current scene of
      epidemiological and public health journals, databases and professional education
      in three Western European languages: French, German and Italian, and examines the
      dynamics and struggles they have today.

PMID- 18826571
TI  - Adolescent idiopathic scoliosis - to operate or not? A debate article.
AB  - Adolescent idiopathic scoliosis (AIS) represents a rare condition with a
      potentially detrimental impact on young patients. Despite vast clinical research
      and published treatment guidelines and algorithms, the optimal therapeutic choice
      for these patients remains highly controversial. While advocates of early surgery
      emphasize the benefits of surgical deformity correction with regard to physical
      and psychological outcome, the opponents base their arguments on the high risk of
      complications and a lack of documented subjective long-term outcome. In the
      present paper, the authors were invited to debate the opposite positions of "pro"
      versus "contra" surgical treatment of AIS, based on the currently available
      evidence and published guidelines.

PMID- 18826572
TI  - Resilin and chitinous cuticle form a composite structure for energy storage in
      jumping by froghopper insects.
AB  - BACKGROUND: Many insects jump by storing and releasing energy in elastic
      structures within their bodies. This allows them to release large amounts of
      energy in a very short time to jump at very high speeds. The fastest of the
      insect jumpers, the froghopper, uses a catapult-like elastic mechanism to achieve
      their jumping prowess in which energy, generated by the slow contraction of
      muscles, is released suddenly to power rapid and synchronous movements of the
      hind legs. How is this energy stored? RESULTS: The hind coxae of the froghopper
      are linked to the hinges of the ipsilateral hind wings by pleural arches, complex
      bow-shaped internal skeletal structures. They are built of chitinous cuticle and
      the rubber-like protein, resilin, which fluoresces bright blue when illuminated
      with ultra-violet light. The ventral and posterior end of this fluorescent region
      forms the thoracic part of the pivot with a hind coxa. No other structures in the
      thorax or hind legs show this blue fluorescence and it is not found in larvae
      which do not jump. Stimulating one trochanteral depressor muscle in a pattern
      that simulates its normal action, results in a distortion and forward movement of
      the posterior part of a pleural arch by 40 microm, but in natural jumping, the
      movement is at least 100 microm. CONCLUSION: Calculations showed that the resilin
      itself could only store 1% to 2% of the energy required for jumping. The stiffer
      cuticular parts of the pleural arches could, however, easily meet all the energy
      storage needs. The composite structure therefore, combines the stiffness of the
      chitinous cuticle with the elasticity of resilin. Muscle contractions bend the
      chitinous cuticle with little deformation and therefore, store the energy needed
      for jumping, while the resilin rapidly returns its stored energy and thus
      restores the body to its original shape after a jump and allows repeated jumping.

PMID- 18826573
TI  - Dried blood spots as a source of anti-malarial antibodies for epidemiological
      studies.
AB  - BACKGROUND: Blood spots collected onto filter paper are an established and
      convenient source of antibodies for serological diagnosis and epidemiological
      surveys. Although recommendations for the storage and analysis of small molecule
      analytes in blood spots exist, there are no published systematic studies of the
      stability of antibodies under different storage conditions. METHODS: Blood spots,
      on filter paper or glass fibre mats and containing malaria-endemic plasma, were
      desiccated and stored at various temperatures for different times. Eluates of
      these spots were assayed for antibodies against two Plasmodium falciparum
      antigens, MSP-119 and MSP2, and calculated titres used to fit an exponential
      (first order kinetic) decay model. The first order rate constants (k) for each
      spot storage temperature were used to fit an Arrhenius equation, in order to
      estimate the thermal and temporal stability of antibodies in dried blood spots.
      The utility of blood spots for serological assays was confirmed by comparing
      antibodies eluted from blood spots with the equivalent plasma values in a series
      of samples from North Eastern Tanzania and by using blood spot-derived antibodies
      to estimate malaria transmission intensity in this site and for two localities in
      Uganda. RESULTS: Antibodies in spots on filter paper and glass fibre paper had
      similar stabilities but blood was more easily absorbed onto filter papers than
      glass fibre, spots were more regular and spot size was more closely correlated
      with blood volume for filter paper spots. Desiccated spots could be stored at or
      below 4 degrees C for extended periods, but were stable for only very limited
      periods at ambient temperature. When desiccated, recoveries of antibodies that
      are predominantly of IgG1 or IgG3 subclasses were similar. Recoveries of
      antibodies from paired samples of serum and of blood spots from Tanzania which
      had been suitably stored showed similar recoveries of antibodies, but spots which
      had been stored for extended periods at ambient humidity and temperature showed
      severe loss of recoveries. Estimates of malaria transmission intensity obtained
      from serum and from blood spots were similar, and values obtained using blood
      spots agreed well with entomologically determined values. CONCLUSION: This study
      has demonstrated the suitability of filter paper blood spots paper for collection
      of serum antibodies, and provided clear guidelines for the treatment and storage
      of filter papers which emphasize the importance of desiccation and minimisation
      of time spent at ambient temperatures. A recommended protocol for collecting,
      storing and assaying blood spots is provided.

PMID- 18826574
TI  - Pulmonary tuberculosis among people living with HIV/AIDS attending care and
      treatment in rural northern Tanzania.
AB  - BACKGROUND: Tuberculosis is the commonest opportunistic infection and the number
      one cause of death in HIV/AIDS patients in developing countries. To address the
      extent of the tuberculosis HIV coinfection in rural Tanzania we conducted a cross
      sectional study including HIV/AIDS patients attending care and treatment clinic
      from September 2006 to March 2007. METHODS: Sputum samples were collected for
      microscopy, culture and drug susceptibility testing. Chest X-ray was done for
      those patients who consented. Blood samples were collected for CD4+ T cells
      count. RESULTS: The prevalence of tuberculosis was 20/233 (8.5%). Twenty (8.5%)
      sputum samples were culture positive. Eight of the culture positive samples (40%)
      were smear positive. Fifteen (75%) of these patients neither had clinical
      symptoms nor chest X-ray findings suggestive of tuberculosis. Nineteen isolates
      (95%) were susceptible to rifampicin, isoniazid, streptomycin and ethambutol (the
      first line tuberculosis drugs). One isolate (5%) from HIV/tuberculosis coinfected
      patients was resistant to isoniazid. No cases of multi- drug resistant
      tuberculosis were identified. CONCLUSION: We found high prevalence of
      tuberculosis disease in this setting. Chest radiograph suggestive of tuberculosis
      and clinical symptoms of fever and cough were uncommon findings in
      HIV/tuberculosis coinfected patients. Tuberculosis can occur at any stage of
      CD4+T cells depletion.

PMID- 18826575
TI  - Complaints handling in hospitals: an empirical study of discrepancies between
      patients' expectations and their experiences.
AB  - BACKGROUND: Many patients are dissatisfied with the way in which their complaints
      about health care are dealt with. This study tested the assumption that this
      dissatisfaction consists - in part at least - of unmet expectations. METHODS:
      Subjects were 279 patients who lodged a complaint with the complaints committees
      of 74 hospitals in the Netherlands. They completed two questionnaires; one on
      their expectations at the start of the complaints handling process, and one on
      their experiences after the complaints procedure (pre-post design; response 50%).
      Dependent variables are patients' satisfaction and their feeling that justice was
      done; independent variables are the association between patients' expectations
      and their experiences. RESULTS: Only 31% of the patients felt they had received
      justice from the complaints process.Two thirds of the patients were satisfied
      with the conduct of the complaints committee, but fewer were satisfied with the
      conduct of the hospital or the medical professional (29% and 18%). Large
      discrepancies between expectations and experiences were found in the case of
      doctors not admitting errors when errors had been made, and of hospital
      managements not providing information on corrective measures that were taken.
      Discrepancies collectively explained 51% of patients' dissatisfaction with the
      committee and one third of patients' dissatisfaction with the hospital and the
      professional. The feeling that justice was done was influenced by the decision on
      the complaint (well-founded or not), but also by the satisfaction with the
      conduct of the committee, the hospital management and the professional involved.
      CONCLUSION: It is disappointing to observe that less than one third of the
      patients felt that justice had been done through the complaints handling process.
      This study shows that the feeling that justice had been done is not only
      influenced by the judgement of the complaints committee, but also by the response
      of the professional. Furthermore, hospitals and professionals should communicate
      on how they are going to prevent a recurrence of the events that led to the
      complaint.

PMID- 18826576
TI  - Midbrain dopaminergic neuron fate specification: Of mice and embryonic stem
      cells.
AB  - The midbrain dopaminergic (mDA) neurons of the substantia nigra and the ventral
      tegmental area play a fundamental role in the control of voluntary movement and
      the regulation of emotion, and are severely affected in Parkinson's disease.
      Recent advances in mouse genetics and vertebrate development have provided us
      with insight into the genetic cascades involved in the development of mDA
      neurons, including the induction of mDA neuron progenitors in the ventral
      mesencephalon, the specification of the mDA neuronal fate and the maintenance of
      postmitotic mDA neurons. In parallel, rapid progress has been made in the
      generation of DA neurons from pluripotent stem cells and the development of stem
      cell-based therapies for Parkinson's disease. Here, we summarize the new findings
      via the developmental progression of mDA neurons and outline how this knowledge
      has been exploited to develop novel paradigms for the in vitro generation of
      these neurons from embryonic stem cells.

PMID- 18826577
TI  - CXCR4 expression in papillary thyroid carcinoma: induction by nitric oxide and
      correlation with lymph node metastasis.
AB  - BACKGROUND: Metastasis to regional lymph nodes is a common step in the
      progression of cancer. Recent evidence suggests that tumor production of CXCR4
      promotes lymph node metastasis. Nitric oxide (NO) may also increase metastatic
      ability in human cancers. METHODS: Nitrite/nitrate levels and functional CXCR4
      expression were assessed in K1 and B-CPAP papillary thyroid carcinoma (PTC) cells
      after induction and/or inhibition of NO synthesis. CXCR4 expression was also
      analyzed in primary human PTC. The relationship between nitrotyrosine levels,
      which are a biomarker for peroxynitrate formation from NO in vivo, CXCR4
      expression, and lymph node status was also analyzed. RESULTS: Production of
      nitrite/nitrate and functional CXCR4 expression in both cell lines was increased
      by treatment with the NO donor DETA NONOate. The NOS inhibitor L-NAME eliminated
      this increase. Positive CXCR4 immunostaining was observed in 60.7% (34/56) of
      PTCs. CXCR4 expression was significantly correlated with nitrotyrosine levels and
      lymph node metastasis in human PTC. CONCLUSION: Our data indicate that NO
      stimulates CXCR4 expression in vitro. Formation of the NO biomarker nitrotyrosine
      was also correlated with CXCR4 expression and lymph node metastasis in human PTC.
      NO may induce lymph node metastasis via CXCR4 induction in papillary thyroid
      carcinoma.

PMID- 18826578
TI  - Low grade papillary transitional cell carcinoma pelvic recurrence masquerading as
      high grade invasive carcinoma, ten years after radical cystectomy.
AB  - BACKGROUND: Tumor recurrence following radical cystectomy for a low-grade
      superficial transitional cell carcinoma (TCC) is exceedingly uncommon and has not
      been reported previously. CASE PRESENTATION: We describe a case of a young male
      presenting with anorexia, weight loss and a large, painful locally destructive
      pelvic recurrence, ten years after radical cystoprostatectomy. The pathology was
      consistent with a low-grade urothelial carcinoma. After an unsuccessful treatment
      with cisplatin-based chemotherapy, the patient underwent a curative intent
      hemipelvectomy with complete excision of tumor and is disease free at one year
      follow-up. CONCLUSION: A literature review related to this unusual presentation
      is reported and a surgical solutions over chemotherapy and radiotherapy is
      proposed.

PMID- 18826579
TI  - Weekly intra-articular injections of bone morphogenetic protein-7 inhibits
      osteoarthritis progression.
AB  - INTRODUCTION: We investigated the ability of a weekly intra-articular injection
      of bone morphogenetic protein (BMP)-7 to prevent osteoarthritis in rabbits with
      anterior cruciate ligament transections. METHODS: First, 36 knee joints were
      randomly divided into four groups: 50, 500, 5,000 ng BMP-7, and control. Knee
      cartilage was evaluated at 4, 8, and 12 weeks. Then, in order to control for
      individual differences, 500 ng BMP-7 was injected into one knee and phosphate
      buffered saline (PBS) into the other, and the two knees were compared at 4, 8,
      and 12 weeks (n = 5). For pharmacokinetic analysis, cartilage was harvested at 1
      hour and 1, 2, 4, and 7 days after knee injection of 500 ng BMP-7 or PBS (n = 3).
      RESULTS: Histological scores in the 500 and 5,000 ng BMP-7 groups were
      significantly better than those in the other groups at 12 weeks. Matched pair
      analysis demonstrated that both macroscopic and histological scores in the 500 ng
      BMP-7 group were better than those in the control group. Immunohistochemical
      analysis revealed higher BMP-7 expression by chondrocytes in the BMP-7 injected
      knees. Histology of whole knee and quantitative micro computed tomography
      analysis showed that weekly injections of 500 ng BMP-7 did not induce synovial
      fibrosis, ectopic bone, or osteophyte formation. As detected by enzyme-linked
      immunosorbent assay, BMP-7 concentration in the cartilage tissue was still higher
      in the BMP-7 treated group 7 days after the injection. CONCLUSIONS: Weekly intra
      articular injections of BMP-7 inhibited progression of osteoarthritis. Obvious
      adverse effects were not observed. BMP-7 concentration and expression in
      cartilage were still higher 7 days after injection.

PMID- 18826581
TI  - A Japanese version of the Perceived Stress Scale: cross-cultural translation and
      equivalence assessment.
AB  - BACKGROUND: This paper describes the development of a Japanese version of the
      Perceived Stress Scale (PSS), and examines the equivalence between the original
      and translated version. The PSS is one of the few instruments to measure a global
      level of perceived stress, and has been widely used in a range of clinical and
      research settings. The PSS has already been translated into several languages,
      but there is no validated Japanese version. METHODS: A forward-backward procedure
      was implemented. Multiple forward and backward translations were produced, and a
      panel of reviewers verified conceptual and semantic equivalence between the
      source and final versions. Non-professional translators who were not brought up
      in bilingual families were used in order to enhance representativeness of
      language in the target populations. The PSS was administered to 222 native
      English speakers and the Japanese version (PSS-J) to 1320 native Japanese
      speakers. RESULTS: Factor analysis showed similar factor loadings of the items
      and satisfactory factorial agreement between the PSS and PSS-J. Cronbach's alpha
      coefficient was high for both versions and for each factor. CONCLUSION: It is
      concluded that the PSS and PSS-J are substantially equivalent and suited for use
      in comparative cross-cultural studies.

PMID- 18826580
TI  - The missing link: Bordetella petrii is endowed with both the metabolic
      versatility of environmental bacteria and virulence traits of pathogenic
      Bordetellae.
AB  - BACKGROUND: Bordetella petrii is the only environmental species hitherto found
      among the otherwise host-restricted and pathogenic members of the genus
      Bordetella. Phylogenetically, it connects the pathogenic Bordetellae and
      environmental bacteria of the genera Achromobacter and Alcaligenes, which are
      opportunistic pathogens. B. petrii strains have been isolated from very different
      environmental niches, including river sediment, polluted soil, marine sponges and
      a grass root. Recently, clinical isolates associated with bone degenerative
      disease or cystic fibrosis have also been described. RESULTS: In this manuscript
      we present the results of the analysis of the completely annotated genome
      sequence of the B. petrii strain DSMZ12804. B. petrii has a mosaic genome of
      5,287,950 bp harboring numerous mobile genetic elements, including seven large
      genomic islands. Four of them are highly related to the clc element of
      Pseudomonas knackmussii B13, which encodes genes involved in the degradation of
      aromatics. Though being an environmental isolate, the sequenced B. petrii strain
      also encodes proteins related to virulence factors of the pathogenic Bordetellae,
      including the filamentous hemagglutinin, which is a major colonization factor of
      B. pertussis, and the master virulence regulator BvgAS. However, it lacks all
      known toxins of the pathogenic Bordetellae. CONCLUSION: The genomic analysis
      suggests that B. petrii represents an evolutionary link between free-living
      environmental bacteria and the host-restricted obligate pathogenic Bordetellae.
      Its remarkable metabolic versatility may enable B. petrii to thrive in very
      different ecological niches.

PMID- 18826582
TI  - Patient satisfaction with primary care: an observational study comparing
      anthroposophic and conventional care.
AB  - BACKGROUND: This study is part of a cross-sectional evaluation of complementary
      medicine providers in primary care in Switzerland. It compares patient
      satisfaction with anthroposophic medicine (AM) and conventional medicine (CON).
      METHODS: We collected baseline data on structural characteristics of the
      physicians and their practices and health status and demographics of the
      patients. Four weeks later patients assessed their satisfaction with the received
      treatment (five items, four point rating scale) and evaluated the praxis care
      (validated 23-item questionnaire, five point rating scale). 1946 adult patients
      of 71 CON and 32 AM primary care physicians participated. RESULTS: 1. Baseline
      characteristics: AM patients were more likely female (75.6% vs. 59.0%, p < 0.001)
      and had higher education (38.6% vs. 24.7%, p < 0.001). They suffered more often
      from chronic illnesses (52.8% vs. 46.2%, p = 0.015) and cancer (7.4% vs. 1.1%).
      AM consultations lasted on average 23,3 minutes (CON: 16,8 minutes, p < 0.001).
      2. Satisfaction: More AM patients expressed a general treatment satisfaction
      (56.1% vs. 43.4%, p < 0.001) and saw their expectations completely fulfilled at
      follow-up (38.7% vs. 32.6%, p < 0.001). AM patients reported significantly fewer
      adverse side effects (9.3% vs. 15.4%, p = 0.003), and more other positive effects
      from treatment (31.7% vs. 17.1%, p < 0.001). Europep: AM patients appreciated
      that their physicians listened to them (80.0% vs. 67.1%, p < 0.001), spent more
      time (76.5% vs. 61.7%, p < 0.001), had more interest in their personal situation
      (74.6% vs. 60.3%, p < 0.001), involved them more in decisions about their medical
      care (67.8% vs. 58.4%, p = 0.022), and made it easy to tell the physician about
      their problems (71.6% vs. 62.9%, p = 0.023). AM patients gave significantly
      better rating as to information and support (in 3 of 4 items p [less than or
      equal to] 0.044) and for thoroughness (70.4% vs. 56.5%, p < 0.001). CONCLUSION:
      AM patients were significantly more satisfied and rated their physicians as
      valuable partners in the treatment. This suggests that subject to certain
      limitations, AM therapy may be beneficial in primary care. To confirm this, more
      detailed qualitative studies would be necessary.

PMID- 18826583
TI  - The effects of thermal capsulorrhaphy of medial parapatellar capsule on patellar
      lateral displacement.
AB  - BACKGROUND: The effectiveness of thermal shrinkage on the medial parapatellar
      capsule for treating recurrent patellar dislocation is controversial. One of
      reasons why it is still controversial is that the effectiveness is still
      qualitatively measured. The purpose of this study was to quantitatively determine
      the immediate effectiveness of the medial parapatellar capsule shrinkage as in
      clinical setting. METHODS: Nine cadaveric knees were used to collect lateral
      displacement data before and after medial shrinkage or open surgery. The force
      and displacement were recorded while a physician pressed the patella from the
      medial side to mimic the physical exam used in clinic. Ten healthy subjects were
      used to test the feasibility of the technique on patients and establish normal
      range of lateral displacement of the patella under a medial force. The force
      applied, the resulting displacement and the ratio of force over displacement were
      compared among four data groups (normal knees, cadaveric knees before medial
      shrinkage, after shrinkage and after open surgery). RESULTS: Displacements of the
      cadaveric knees both before and after thermal modification were similar to normal
      subjects, and the applied forces were significantly higher. No significant
      differences were found between before and after thermal modification groups.
      After open surgery, displacements were reduced significantly while applied forces
      were significantly higher. CONCLUSION: No immediate difference was found after
      thermal shrinkage of the medial parapatellar capsule. Open surgery immediately
      improved of the lateral stiffness of the knee capsule.

PMID- 18826584
TI  - Neuroprotective efficacy and therapeutic window of curcuma oil: in rat embolic
      stroke model.
AB  - BACKGROUND: Among the naturally occurring compounds, turmeric from the dried
      rhizome of the plant Curcuma longa has long been used extensively as a condiment
      and a household remedy all over Southeast Asia. Turmeric contains essential oil,
      yellow pigments (curcuminoids), starch and oleoresin. The present study was
      designed for investigating the neuroprotective efficacy and the time window for
      effective therapeutic use of Curcuma oil (C. oil). METHOD: In the present study,
      the effect of post ischemic treatment of C.oil after ischemia induced by
      occlusion of the middle cerebral artery in the rat was observed. C.oil (500 mg/kg
      body wt) was given 4 hrs post ischemia. The significant effect on lesion size as
      visualized by using diffusion-weighted magnetic resonance imaging and neuroscore
      was still evident when treatment was started 4 hours after insult. Animals were
      assessed for behavioral deficit scores after 5 and 24 hours of ischemia.
      Subsequently, the rats were sacrificed for evaluation of infarct and edema
      volumes and other parameters. RESULTS: C.oil ameliorated the ischemia induced
      neurological functional deficits and the infarct and edema volumes measured after
      5 and 24 hrs of ischemia. After 24 hrs, immunohistochemical and Western blot
      analysis demonstrated that the expression of iNOS, cytochrome c and Bax/Bcl-2
      were altered after the insult, and antagonized by treatment with C.oil. C.oil
      significantly reduced nitrosative stress, tended to correct the decreased
      mitochondrial membrane potential, and also affected caspase-3 activation finally
      apoptosis. CONCLUSION: Here we demonstrated that iNOS-derived NO produced during
      ischemic injury was crucial for the up-regulation of ischemic injury targets.
      C.oil down-regulates these targets this coincided with an increased survival rate
      of neurons.

PMID- 18826585
TI  - Sensitivity of imaging for multifocal-multicentric breast carcinoma.
AB  - BACKGROUND: This retrospective study aims to determine: 1) the sensitivity of
      preoperative mammography (Mx) and ultrasound (US), and re-reviewed Mx to detect
      multifocal multicentric breast carcinoma (MMBC), defined by pathology on surgical
      specimens, and 2) to analyze the characteristics of both detected and undetected
      foci on Mx and US. METHODS: Three experienced breast radiologists re-reviewed,
      independently, digital mammography of 97 women with MMBC pathologically diagnosed
      on surgical specimens. The radiologists were informed of all neoplastic foci, and
      blinded to the original mammograms and US reports. With regards to Mx, they
      considered the breast density, number of foci, the Mx characteristics of the
      lesions and their BI-RADS classification. For US, they considered size of the
      lesions, BI-RADS classification and US pattern and lesion characteristics.
      According to the histological size, the lesions were classified as: index cancer,
      2nd lesion, 3rd lesion, and 4th lesion. Any pathologically identified malignant
      foci not previously described in the original imaging reports, were defined as
      undetected or missed lesions. Sensitivity was calculated for Mx, US and re
      reviewed Mx for detecting the presence of the index cancer as well as additional
      satellite lesions. RESULTS: Pathological examination revealed 13 multifocal and
      84 multicentric cancers with a total of 303 malignant foci (282 invasive and 21
      non invasive). Original Mx and US reports had an overall sensitivity of 45.5% and
      52.9%, respectively. Mx detected 83/97 index cancers with a sensitivity of 85.6%.
      The number of lesions undetected by original Mx was 165/303. The Mx pattern of
      breasts with undetected lesions were: fatty in 3 (1.8%); scattered fibroglandular
      density in 40 (24.3%), heterogeneously dense in 91 (55.1%) and dense in 31
      (18.8%) cases. In breasts with an almost entirely fatty pattern, Mx sensitivity
      was 100%, while in fibroglandular or dense pattern it was reduced to 45.5%. Re
      reviewed Mx detected only 3 additional lesions. The sensitivity of Mx was
      affected by the presence of dense breast tissue which obscured lesions or by an
      incorrect interpretation of suspicious findings.US detected 73/80 index cancers
      (sensitivity of 91.2%), US missed 117 malignant foci with a mean tumor diameter
      of 6.5 mm; the sensitivity was 52.9%Undetected lesions by US were those smallest
      in size and present in fatty breast or in the presence of microcalcifications
      without a visible mass.US sensitivity was affected by the presence of fatty
      tissue or by the extent of calcification. CONCLUSION: Mx missed MMBC malignant
      foci more often in dense or fibroglandular breasts. US missed small lesions in
      mainly fatty breasts or when there were only microcalcifications. The combined
      sensitivity of both techniques to assess MMBC was 58%. We suggest larger studies
      on multimodality imaging.

PMID- 18826586
TI  - Cloning, characterisation and comparative analysis of a starch synthase IV gene
      in wheat: functional and evolutionary implications.
AB  - BACKGROUND: Starch is of great importance to humans as a food and biomaterial,
      and the amount and structure of starch made in plants is determined in part by
      starch synthase (SS) activity. Five SS isoforms, SSI, II, III, IV and Granule
      Bound SSI, have been identified, each with a unique catalytic role in starch
      synthesis. The basic mode of action of SSs is known; however our knowledge of
      several aspects of SS enzymology at the structural and mechanistic level is
      incomplete. To gain a better understanding of the differences in SS sequences
      that underscore their specificity, the previously uncharacterised SSIVb from
      wheat was cloned and extensive bioinformatics analyses of this and other SSs
      sequences were done. RESULTS: The wheat SSIV cDNA is most similar to rice SSIVb
      with which it shows synteny and shares a similar exon-intron arrangement. The
      wheat SSIVb gene was preferentially expressed in leaf and was not regulated by a
      circadian clock. Phylogenetic analysis showed that in plants, SSIV is closely
      related to SSIII, while SSI, SSII and Granule Bound SSI clustered together and
      distinctions between the two groups can be made at the genetic level and included
      chromosomal location and intron conservation. Further, identified differences at
      the amino acid level in their glycosyltransferase domains, predicted secondary
      structures, global conformations and conserved residues might be indicative of
      intragroup functional associations. CONCLUSION: Based on bioinformatics analysis
      of the catalytic region of 36 SSs and 3 glycogen synthases (GSs), it is suggested
      that the valine residue in the highly conserved K-X-G-G-L motif in SSIII and SSIV
      may be a determining feature of primer specificity of these SSs as compared to
      GBSSI, SSI and SSII. In GBSSI, the Ile485 residue may partially explain that
      enzyme's unique catalytic features. The flexible 380s Loop in the starch
      catalytic domain may be important in defining the specificity of action for each
      different SS and the G-X-G in motif VI could define SSIV and SSIII action
      particularly.

PMID- 18826587
TI  - Brain serotonin and dopamine modulators, perceptual responses and endurance
      performance during exercise in the heat following creatine supplementation.
AB  - BACKGROUND: The present experiment examined the responses of peripheral
      modulators and indices of brain serotonin (5-HT) and dopamine (DA) function and
      their association with perception of effort during prolonged exercise in the heat
      after creatine (Cr) supplementation. METHODS: Twenty one endurance-trained males
      performed, in a double-blind fashion, two constant-load exercise tests to
      exhaustion at 63 +/- 5% V(O2) max in the heat (ambient temperature: 30.3 +/- 0.5
      degrees C, relative humidity: 70 +/- 2%) before and after 7 days of Cr (20 g.d-1
      Cr + 140 g.d-1 glucose polymer) or placebo (Plc) (160 g.d-1 glucose polymer)
      supplementation. RESULTS: 3-way interaction has shown that Cr supplementation
      reduced rectal temperature, heart rate, ratings of perceived leg fatigue (P <
      0.05), plasma free-tryptophan (Trp) (P < 0.01) and free-Trp:tyrosine ratio (P <
      0.01) but did not influence the ratio of free-Trp:large neutral amino acids or
      contribute in improving endurance performance (Plc group, n = 10: 50.4 +/- 8.4
      min vs. 51.2 +/- 8.0 min, P > 0.05; Cr group, n = 11: 47.0 +/- 4.7 min vs. 49.7
      +/- 7.5 min, P > 0.05). However, after dividing the participants into
      "responders" and "non-responders" to Cr, based on their intramuscular Cr uptake,
      performance was higher in the "responders" relative to "non-responders" group
      (51.7 +/- 7.4 min vs.47.3 +/- 4.9 min, p < 0.05). CONCLUSION: Although Cr
      influenced key modulators of brain 5-HT and DA function and reduced various
      thermophysiological parameters which all may have contributed to the reduced
      effort perception during exercise in the heat, performance was improved only in
      the "responders" to Cr supplementation. The present results may also suggest the
      demanding of the pre-experimental identification of the participants into
      "responders" and "non-responders" to Cr supplementation before performing the
      main experimentation. Otherwise, the possibility of the type II error may be
      enhanced.

PMID- 18826588
TI  - Conjugated linoleic acid content of human plasma.
AB  - Conjugated linoleic acid (CLA), a naturally occurring anticarcinogen found in
      dairy products, is an intermediary product of ruminal biohydrogenation of
      polyunsaturated fatty acids. Few data exist on the CLA content of the human blood
      plasma. The determination of a "normal" content could help in estimating if a
      person consumes satisfactory amounts of CLA with the diet and thus takes
      advantage of its potential beneficial effects on health. The purpose of this
      study was to compare the plasma CLA content of individuals not consuming dairy
      products (group 1, n = 12), individuals consuming normal amounts of dairy
      products (group 2, n = 77) and individuals consuming CLA supplement (group 3, n =
      12). The only CLA isomer that presented higher percentage than the detection
      limit (0.03% of total fatty acids) was rumenic acid (cis9, trans11
      octadecadienoic acid). An interesting finding is that compared to the other two
      groups, group 3 members show the highest average plasma content in rumenic acid,
      i.e. 0.20% of total fatty acids. The present study could be characterized as the
      first step in the direction of establishing a normal CLA content of human plasma.
      Based on these results, it could be suggested that the lower limit of the plasma
      CLA content is approximately 0.1% of total fatty acids.

PMID- 18826589
TI  - Quality assessment parameters for EST-derived SNPs from catfish.
AB  - BACKGROUND: SNPs are abundant, codominantly inherited, and sequence-tagged
      markers. They are highly adaptable to large-scale automated genotyping, and
      therefore, are most suitable for association studies and applicable to
      comparative genome analysis. However, discovery of SNPs requires genome
      sequencing efforts through whole genome sequencing or deep sequencing of reduced
      representation libraries. Such genome resources are not yet available for many
      species including catfish. A large resource of ESTs is to become available in
      catfish allowing identification of large number of SNPs, but reliability of EST
      derived SNPs are relatively low because of sequencing errors. This project was
      designed to answer some of the questions relevant to quality assessment of EST
      derived SNPs. RESULTS: wo factors were found to be most significant for
      validation of EST-derived SNPs: the contig size (number of sequences in the
      contig) and the minor allele sequence frequency. The larger the contigs were, the
      greater the validation rate although the validation rate was reasonably high when
      the contigs contain four or more EST sequences with the minor allele sequence
      being represented at least twice in the contigs. Sequence quality surrounding the
      SNP under test is also crucially important. PCR extension appeared to be limited
      to a very short distance, prohibiting successful genotyping when an intron was
      present, a surprising finding. CONCLUSION: Stringent quality assessment measures
      should be used when working with EST-derived SNPs. In particular, contigs
      containing four or more ESTs should be used and the minor allele sequence should
      be represented at least twice. Genotyping primers should be designed from a
      single exon, completely avoiding introns. Application of such quality assessment
      measures, along with large resources of ESTs, should provide effective means for
      SNP identification in species where genome sequence resources are lacking.

PMID- 18826590
TI  - The 'cardiac-lung mass' artifact: an echocardiographic sign of lung atelectasis
      and/or pleural effusion.
AB  - INTRODUCTION: We conducted an ultrasound study to investigate echocardiographic
      artifacts in mechanically ventilated patients with lung pathology. METHODS: A
      total of 205 mechanically ventilated patients who exhibited lung atelectasis
      and/or pleural effusion were included in this 36-month study. The patients
      underwent lung echography and transthoracic echocardiography, with a linear 5 to
      10 MHz and with a 1.5 to 3.6 MHz wide-angle phased-array transducer,
      respectively. Patients were examined by two experienced observers who were
      blinded to each other's interpretation. RESULTS: A total of 124 patients (60,48%)
      were hospitalized because of multiple trauma; 60 patients (29,26%) because of
      respiratory insufficiency, and 21 (10,24%) because of recent postoperative
      surgery. The mean duration ( +/- standard deviation) of hospitalization was 35 +/
      27 days. An intracardiac artifact was documented in 17 out of 205 patients
      (8.29%) by echocardiography. It was visible only in the apical views, whereas
      subsequent transesophageal echocardiography revealed no abnormalities. The
      artifact consisted of a mobile component that exhibited, on M-mode, a pattern of
      respiratory variation similar to the lung 'sinusoid sign'. Lung echography
      revealed lung atelectasis and/or pleural effusion adjacent to the heart, and a
      similar M-mode pattern was observed. The artifact was recorded within the left
      cardiac chambers in 11 cases and within the right cardiac chambers in six.
      CONCLUSIONS: Lung atelectasis and/or pleural effusion may create a mirror image,
      intracardiac artifact in mechanically ventilated patients. The latter was named
      the 'cardiac-lung mass' artifact to underline the important diagnostic role of
      both echocardiography and lung echography in these patients. TRIAL REGISTRATION:
      This trial is ISRCTN registered: ISRCTN 49216096.

PMID- 18826591
TI  - Induction- and conditioning-protocol dependent involvement of NR2B-containing
      NMDA receptors in synaptic potentiation and contextual fear memory in the
      hippocampal CA1 region of rats.
AB  - Long-term potentiation (LTP) in the hippocampal CA1 region requires the
      activation of N-methyl-D-aspartate receptors (NMDARs). Studies using genetic and
      pharmacological approaches have reported inconsistent results of the requirement
      of NR2B-containing NMDARs in LTP in the CA1 region. Pharmacological studies
      showed that NR2B-containing NMDARs are not required for LTP, while genetic
      studies reported that over-expression of NR2B-NMDARs enhances LTP and hippocampus
      dependent memory. Here, we provide evidence showing that the functional role of
      NR2B-NMDARs in hippocampal LTP and memory depends on LTP-inducing and behavior
      conditioning protocols. Inhibition of NR2B-NMDARs with the NR2B selective
      antagonist ifenprodil or Ro25-6981 suppressed LTP induced by spike-timing
      protocol, with no impact on LTP induced by pairing protocol or two-train high
      frequency stimulation (HFS) protocol. Inhibition of NR2B-NMDARs did not affect
      the late phase LTP induced by four-train HFS. Ca2(+) imaging showed that there
      was difference in kinetics of intracellular Ca2(+) signals induced by spiking
      timing and pairing protocols. Pre-training intra-CA1 infusion of ifenprodil or
      Ro25-6981 impaired the contextual fear memory induced by five CS-US pairings,
      with no effect on the memory induced by one CS-US pairing.

PMID- 18826592
TI  - Public health and epidemiology journals published in Brazil and other Portuguese
      speaking countries.
AB  - It is well known that papers written in languages other than English have a great
      risk of being ignored simply because these languages are not accessible to the
      international scientific community. The objective of this paper is to facilitate
      the access to the public health and epidemiology literature available in
      Portuguese speaking countries. It was found that it is particularly concentrated
      in Brazil, with some few examples in Portugal and none in other Portuguese
      speaking countries. This literature is predominantly written in Portuguese, but
      also in other languages such as English or Spanish. The paper describes the
      several journals, as well as the bibliographic databases that index these
      journals and how to access them. Most journals provide open-access with direct
      links in the indexing databases. The importance of this scientific production for
      the development of epidemiology as a scientific discipline and as a basic
      discipline for public health practice is discussed. To marginalize these
      publications has implications for a more balanced knowledge and understanding of
      the health problems and their determinants at a world-wide level.

PMID- 18826593
TI  - Acute liver failure due to primary angiosarcoma: a case report and review of
      literature.
AB  - BACKGROUND: Hepatic angiosarcoma is a primary sarcoma of the liver, accounting
      for only 2% of all primary hepatic malignancies. Acute liver failure is an
      extremely rare presentation of a primary liver tumour. CASE PRESENTATION: We
      report a case of a seventy year-old man who presented with a very short period of
      jaundice leading to fulminant hepatic failure (FHF). On further investigation he
      was found to have primary angiosarcoma of liver. CONCLUSION: The treatment
      outcomes for hepatic angiosarcoma are poor, we discuss the options available and
      the need for prompt investigation and establishment of a diagnosis.

PMID- 18826594
TI  - Costs and cost-effectiveness of delivering intermittent preventive treatment
      through schools in western Kenya.
AB  - BACKGROUND: Awareness of the potential impact of malaria among school-age
      children has stimulated investigation into malaria interventions that can be
      delivered through schools. However, little evidence is available on the costs and
      cost-effectiveness of intervention options. This paper evaluates the costs and
      cost-effectiveness of intermittent preventive treatment (IPT) as delivered by
      teachers in schools in western Kenya. METHODS: Information on actual drug and non
      drug associated costs were collected from expenditure and salary records,
      government budgets and interviews with key district and national officials.
      Effectiveness data were derived from a cluster-randomised-controlled trial of IPT
      where a single dose of sulphadoxine-pyrimethamine and three daily doses of
      amodiaquine were provided three times in year (once termly). Both financial and
      economic costs were estimated from a provider perspective, and effectiveness was
      estimated in terms of anaemia cases averted. A sensitivity analysis was conducted
      to assess the impact of key assumptions on estimated cost-effectiveness. RESULTS:
      The delivery of IPT by teachers was estimated to cost US$ 1.88 per child treated
      per year, with drug and teacher training costs constituting the largest cost
      components. Set-up costs accounted for 13.2% of overall costs (equivalent to US$
      0.25 per child) whilst recurrent costs accounted for 86.8% (US$ 1.63 per child
      per year). The estimated cost per anaemia case averted was US$ 29.84 and the cost
      per case of Plasmodium falciparum parasitaemia averted was US$ 5.36,
      respectively. The cost per case of anaemia averted ranged between US$ 24.60 and
      40.32 when the prices of antimalarial drugs and delivery costs were varied. Cost
      effectiveness was most influenced by effectiveness of IPT and the background
      prevalence of anaemia. In settings where 30% and 50% of schoolchildren were
      anaemic, cost-effectiveness ratios were US$ 12.53 and 7.52, respectively.
      CONCLUSION: This study provides the first evidence that IPT administered by
      teachers is a cost-effective school-based malaria intervention and merits
      investigation in other settings.

PMID- 18826596
TI  - Juvenile polyposis syndrome affecting the stomach: a case report.
AB  - INTRODUCTION: Juvenile polyposis syndrome(JPS) is a rare autosomal dominant
      inherited condition. Hamartomatous polyps can affect the entire gastrointestinal
      tract but usually predominate in the colon. In this case report we present an
      unusual case of JPS that presented with massive gastric polyposis requiring a
      total gastrectomy. CASE PRESENTATION: A 51-year-old man presented with symptoms
      of gastric outlet obstruction and upper gastrointestinal bleeding. Gastroscopy
      showed massive gastric polyposis with a large antral polyp that had prolapsed
      through the pylorus causing gastric outlet obstruction. Initially endoscopic
      polypectomy was performed, but due to progressive symptoms a total gastrectomy
      was then performed. Histology confirmed massive gastric juvenile polyposis.
      CONCLUSION: Massive gastric polyposis is an uncommon manifestation of juvenile
      polyposis syndrome. This case illustrates important principles in managing this
      condition.

PMID- 18826595
TI  - Differential regulation of morphine antinociceptive effects by endogenous
      enkephalinergic system in the forebrain of mice.
AB  - BACKGROUND: Mice lacking the preproenkephalin (ppENK) gene are hyperalgesic and
      show more anxiety and aggression than wild-type (WT) mice. The marked behavioral
      changes in ppENK knock-out (KO) mice appeared to occur in supraspinal response to
      painful stimuli. However the functional role of enkephalins in the supraspinal
      nociceptive processing and their underlying mechanism is not clear. The aim of
      present study was to compare supraspinal nociceptive and morphine antinociceptive
      responses between WT and ppENK KO mice. RESULTS: The genotypes of bred KO mice
      were confirmed by PCR. Met-enkephalin immunoreactive neurons were labeled in the
      caudate-putamen, intermediated part of lateral septum, lateral globus pallidus,
      intermediated part of lateral septum, hypothalamus, and amygdala of WT mice. Met
      enkephalin immunoreactive neurons were not found in the same brain areas in KO
      mice. Tail withdrawal and von Frey test results did not differ between WT and KO
      mice. KO mice had shorter latency to start paw licking than WT mice in the hot
      plate test. The maximal percent effect of morphine treatments (5 mg/kg and 10
      mg/kg, i.p.) differed between WT and KO mice in hot plate test. The current
      source density (CSD) profiles evoked by peripheral noxious stimuli in the primary
      somatosenstory cortex (S1) and anterior cingulate cortex (ACC) were similar in WT
      and KO mice. After morphine injection, the amplitude of the laser-evoked sink
      currents was decreased in S1 while the amplitude of electrical-evoked sink
      currents was increased in the ACC. These differential morphine effects in S1 and
      ACC were enhanced in KO mice. Facilitation of synaptic currents in the ACC is
      mediated by GABA inhibitory interneurons in the local circuitry. Percent
      increases in opioid receptor binding in S1 and ACC were 5.1% and 5.8%,
      respectively. CONCLUSION: The present results indicate that the endogenous
      enkephalin system is not involved in acute nociceptive transmission in the spinal
      cord, S1, and ACC. However, morphine preferentially suppressed supraspinal
      related nociceptive behavior in KO mice. This effect was reflected in the
      potentiated differential effects of morphine in the S1 and ACC in KO mice. This
      potentiation may be due to an up-regulation of opioid receptors. Thus these
      findings strongly suggest an antagonistic interaction between the endogenous
      enkephalinergic system and exogenous opioid analgesic actions in the supraspinal
      brain structures.

PMID- 18826597
TI  - Rac1 GTPase and the Rac1 exchange factor Tiam1 associate with Wnt-responsive
      promoters to enhance beta-catenin/TCF-dependent transcription in colorectal
      cancer cells.
AB  - BACKGROUND: beta-catenin is a key mediator of the canonical Wnt pathway as it
      associates with members of the T-cell factor (TCF) family at Wnt-responsive
      promoters to drive the transcription of Wnt target genes. Recently, we showed
      that Rac1 GTPase synergizes with beta-catenin to increase the activity of a TCF
      responsive reporter. This synergy was dependent on the nuclear presence of Rac1,
      since inhibition of its nuclear localization effectively abolished the
      stimulatory effect of Rac1 on TCF-responsive reporter activity. We hypothesised
      that Rac1 plays a direct role in enhancing the transcription of endogenous Wnt
      target genes by modulating the beta-catenin/TCF transcription factor complex.
      RESULTS: We employed chromatin immunoprecipitation studies to demonstrate that
      Rac1 associates with the beta-catenin/TCF complex at Wnt-responsive promoters of
      target genes. This association served to facilitate transcription, since
      overexpression of active Rac1 augmented Wnt target gene activation, whereas
      depletion of endogenous Rac1 by RNA interference abrogated this effect. In
      addition, the Rac1-specific exchange factor, Tiam1, potentiated the stimulatory
      effects of Rac1 on the canonical Wnt pathway. Tiam1 promoted the formation of a
      complex containing Rac1 and beta-catenin. Furthermore, endogenous Tiam1
      associated with endogenous beta-catenin, and this interaction was enhanced in
      response to Wnt3a stimulation. Intriguingly, Tiam1 was recruited to Wnt
      responsive promoters upon Wnt3a stimulation, whereas Rac1 was tethered to TCF
      binding elements in a Wnt-independent manner. CONCLUSION: Taken together, our
      results suggest that Rac1 and the Rac1-specific activator Tiam1 are components of
      transcriptionally active beta-catenin/TCF complexes at Wnt-responsive promoters,
      and the presence of Rac1 and Tiam1 within these complexes serves to enhance
      target gene transcription. Our results demonstrate a novel functional mechanism
      underlying the cross-talk between Rac1 and the canonical Wnt signalling pathway.

PMID- 18826598
TI  - Harnessing the wealth of Chinese scientific literature: schistosomiasis research
      and control in China.
AB  - The economy of China continues to boom and so have its biomedical research and
      related publishing activities. Several so-called neglected tropical diseases that
      are most common in the developing world are still rampant or even emerging in
      some parts of China. The purpose of this article is to document the significant
      research potential from the Chinese biomedical bibliographic databases. The
      research contributions from China in the epidemiology and control of
      schistosomiasis provide an excellent illustration. We searched two widely used
      databases, namely China National Knowledge Infrastructure (CNKI) and VIP
      Information (VIP). Employing the keyword "Schistosoma" and covering the period
      1990-2006, we obtained 10,244 hits in the CNKI database and 5,975 in VIP. We
      examined 10 Chinese biomedical journals that published the highest number of
      original research articles on schistosomiasis for issues including languages and
      open access. Although most of the journals are published in Chinese, English
      abstracts are usually available. Open access to full articles was available in
      China Tropical Medicine in 2005/2006 and is granted by the Chinese Journal of
      Parasitology and Parasitic Diseases since 2003; none of the other journals
      examined offered open access. We reviewed (i) the discovery and development of
      antischistosomal drugs, (ii) the progress made with molluscicides and (iii)
      environmental management for schistosomiasis control in China over the past 20
      years. In conclusion, significant research is published in the Chinese
      literature, which is relevant for local control measures and global scientific
      knowledge. Open access should be encouraged and language barriers removed so the
      wealth of Chinese research can be more fully appreciated by the scientific
      community.

PMID- 18826599
TI  - Effect of the assignment of ancestral CpG state on the estimation of nucleotide
      substitution rates in mammals.
AB  - BACKGROUND: Molecular evolutionary studies in mammals often estimate nucleotide
      substitution rates within and outside CpG dinucleotides separately. Frequently,
      in alignments of two sequences, the division of sites into CpG and non-CpG
      classes is based simply on the presence or absence of a CpG dinucleotide in
      either sequence, a procedure that we refer to as CpG/non-CpG assignment. Although
      it likely that this procedure is biased, it is generally assumed that the bias is
      negligible if species are very closely related. RESULTS: Using simulations of DNA
      sequence evolution we show that assignment of the ancestral CpG state based on
      the simple presence/absence of the CpG dinucleotide can seriously bias estimates
      of the substitution rate, because many true non-CpG changes are misassigned as
      CpG. Paradoxically, this bias is most severe between closely related species,
      because a minimum of two substitutions are required to misassign a true ancestral
      CpG site as non-CpG whereas only a single substitution is required to misassign a
      true ancestral non-CpG site as CpG in a two branch tree. We also show that CpG
      misassignment bias differentially affects fourfold degenerate and noncoding sites
      due to differences in base composition such that fourfold degenerate sites can
      appear to be evolving more slowly than noncoding sites. We demonstrate that the
      effects predicted by our simulations occur in a real evolutionary setting by
      comparing substitution rates estimated from human-chimp coding and intronic
      sequence using CpG/non-CpG assignment with estimates derived from a method that
      is largely free from bias. CONCLUSION: Our study demonstrates that a common
      method of assigning sites into CpG and non CpG classes in pairwise alignments is
      seriously biased and recommends against the adoption of ad hoc methods of
      ancestral state assignment.

PMID- 18826600
TI  - Human resources for maternal health: multi-purpose or specialists?
AB  - A crucial question in the aim to attain MDG5 is whether it can be achieved faster
      with the scaling up of multi-purpose health workers operating in the community or
      with the scaling up of professional skilled birth attendants working in health
      facilities. Most advisers concerned with maternal mortality reduction concur to
      promote births in facilities with professional attendants as the ultimate
      strategy. The evidence, however, is scarce on what it takes to progress in this
      path, and on the 'interim solutions' for situations where the majority of women
      still deliver at home. These questions are particularly relevant as we have
      reached the twentieth anniversary of the safe motherhood initiative without much
      progress made. In this paper we review the current situation of human resources
      for maternal health as well as the problems that they face. We propose seven key
      areas of work that must be addressed when planning for scaling up human resources
      for maternal health in light of MDG5, and finally we indicate some advances
      recently made in selected countries and the lessons learned from these
      experiences. Whilst the focus of this paper is on maternal health, it is
      acknowledged that the interventions to reduce maternal mortality will also
      contribute to significantly reducing newborn mortality. Addressing each of the
      seven key areas of work--recommended by the first International Forum on
      'Midwifery in the Community', Tunis, December 2006--is essential for the success
      of any MDG5 programme. We hypothesize that a great deal of the stagnation of
      maternal health programmes has been the result of confusion and careless choices
      in scaling up between a limited number of truly skilled birth attendants and
      large quantities of multi-purpose workers with short training, fewer skills,
      limited authority and no career pathways. We conclude from the lessons learnt
      that no significant progress in maternal mortality reduction can be achieved
      without a strong political decision to empower midwives and others with midwifery
      skills, and a substantial strengthening of health systems with a focus on quality
      of care rather than on numbers, to give them the means to respond to the
      challenge.

PMID- 18826601
TI  - Balance between matrix metalloproteinases (MMP) and tissue inhibitors of
      metalloproteinases (TIMP) in the cervical mucus plug estimated by determination
      of free non-complexed TIMP.
AB  - BACKGROUND: The cervical mucus plug (CMP) is a semi-solid structure with
      antibacterial properties positioned in the cervical canal during pregnancy. The
      CMP contains high concentrations of matrix metalloproteinase 8 and 9 (MMP-8, MMP
      9) and tissue inhibitor of metalloproteinase 1 (TIMP-1). This indicates a
      potential to degrade extracellular matrix components depending on the balance
      between free non-complexed inhibitors and active enzymes. METHODS: Thirty-two
      CMPs collected during active labor at term were analyzed. Twelve CMPs were
      separated into a cellular and an extracellular/fluid phase and analyzed by
      gelatin and reverse zymography to reveal MMP and TIMP location. Twenty samples
      were homogenized, extracted and studied by the TIMP activity assay based on
      gelatin zymography. Enzyme-linked immunosorbent assay (ELISA) was used to
      determine TIMP-1, MMP-8 and MMP-9 protein concentrations, and gelatin and reverse
      zymography used to identify gelatinases and TIMPs, respectively. The Western
      blotting technique was applied for semi-quantification of alpha2-macroglobulin.
      An ELISA activity assay was used to detect MMP-8 and MMP-9 activity. RESULTS:
      ProMMP-2, proMMP-9, TIMP-1 and TIMP-2 were almost exclusively located in the
      fluid phase compared to the cellular phase of the CMP. All the extracted samples
      contained MMP-8, MMP-9, TIMP-1, TIMP-2 and alpha2-macroglobulin. Free non
      complexed TIMP was detected in all the samples analyzed by the TIMP activity
      assay and was associated with TIMP-1 protein (R = 0.71, p < 0.001) and with the
      TIMP/MMP molar ratio (1.7 (1.1-2.5) (mean (95% confidence interval)) (R = 0.65, p
      = 0.002). The ELISA activity assay showed no activity from MMP-8 or MMP-9.
      CONCLUSION: Due to their extracellular location, potential proteolytic activity
      from neutrophil-derived MMPs in the CMP could exert a biological impact on
      cervical dilatation and fetal membrane rupture at term. The functional TIMP
      activity assay, revealing excess non-complexed TIMP, and a molar inhibitor/enzyme
      ratio above unity, indicate that refined MMP control prevents CMP-originated
      proteolytic activity in the surrounding tissue.

PMID- 18826603
TI  - Diagnostic difficulties of Lactobacillus casei bacteraemia in immunocompetent
      patients: a case report.
AB  - INTRODUCTION: Lactobacilli are currently proposed as probiotic agents in several
      dietary products. In blood cultures, they are usually considered as contaminants,
      but in recent years they have been recognized as causal infectious agents of
      endocarditis, urinary tract infections, meningitis, intra-abdominal infections
      and bacteraemia. CASE PRESENTATION: We report a case of Lactobacillus casei
      bacteraemia in a 66-year-old immunocompetent man with a history of fever of
      unknown origin. Leuconostoc bacteraemia was demonstrated by blood culture, but a
      later polymerase chain reaction analysis with sequencing of 16S ribosomal RNA
      identified Lactobacillus casei and a successful antibiotic therapy was performed.
      CONCLUSION: Bacteraemia caused by probiotic organisms is rare but underestimated,
      since they are normally regarded as contaminants and their role as primary
      invaders is not always easily established. Although the consumption of probiotic
      products cannot be considered a risk factor in the development of diseases caused
      by usually non-pathogenic bacteria, specific individual clinical histories should
      be taken into account. This report should alert both clinicians and
      microbiologists to the possibility of unusual pathogens causing serious illnesses
      and to the use of 16S ribosomal RNA sequencing for molecular identification as a
      powerful tool in confirming the diagnosis of infrequent pathogens.

PMID- 18826602
TI  - The fatty acid binding protein 7 (FABP7) is involved in proliferation and
      invasion of melanoma cells.
AB  - BACKGROUND: The molecular mechanisms underlying melanoma tumor development and
      progression are still not completely understood. One of the new candidates that
      emerged from a recent gene expression profiling study is fatty acid-binding
      protein 7 (FABP7), involved in lipid metabolism, gene regulation, cell growth and
      differentiation. METHODS: We studied the functional role of FABP7 in human
      melanoma cell lines and using immunohistochemistry analyzed its expression
      pattern and clinical role in 11 nevi, 149 primary melanomas and 68 metastases.
      RESULTS: FABP7 mRNA and protein level is down-regulated following treatment of
      melanoma cell lines with a PKC activator (PMA) or MEK1 inhibitor (PD98059). Down
      regulation of FABP7 using siRNA decreased cell proliferation and invasion but did
      not affect apoptosis. In clinical specimens, FABP7 was expressed in 91% of nevi,
      71% of primary melanomas and 70% of metastases, with a cytoplasmic and/or nuclear
      localization. FABP7 expression was associated with tumor thickness in superficial
      spreading melanoma (P = 0.021). In addition, we observed a trend for an
      association between FABP7 expression and Ki-67 score (P = 0.070) and shorter
      relapse-free survival (P = 0.069) in this group of patients. CONCLUSION: Our data
      suggest that FABP7 can be regulated by PKC and the MAPK/ERK1/2 pathway through
      independent mechanisms in melanoma cell lines. Furthermore, FABP7 is involved in
      cell proliferation and invasion in vitro, and may be associated with tumor
      progression in melanoma.

PMID- 18826604
TI  - Chinese journals: a guide for epidemiologists.
AB  - Chinese journals in epidemiology, preventive medicine and public health contain
      much that is of potential international interest. However, few non-Chinese
      speakers are acquainted with this literature. This article therefore provides an
      overview of the contemporary scene in Chinese biomedical journal publication,
      Chinese bibliographic databases and Chinese journals in epidemiology, preventive
      medicine and public health. The challenge of switching to English as the medium
      of publication, the development of publishing bibliometric data from Chinese
      databases, the prospect of an Open Access publication model in China, the issue
      of language bias in literature reviews and the quality of Chinese journals are
      discussed. Epidemiologists are encouraged to search the Chinese bibliographic
      databases for Chinese journal articles.

PMID- 18826605
TI  - The need to reform our assessment of evidence from clinical trials: a commentary.
AB  - The ideology of evidence-based medicine (EBM) has dramatically altered the way we
      think, conceptualize, philosophize and practice medicine. One of its major
      pillars is the appraisal and classification of evidence. Although important and
      beneficial, this process currently lacks detail and is in need of reform. In
      particular, it largely focuses on three key dimensions (design, [type I] alpha
      error and beta [type II] error) to grade the quality of evidence and often omits
      other crucial aspects of evidence such as biological plausibility,
      reproducibility, generalizability, temporality, consistency and coherence. It
      also over-values the randomized trial and meta-analytical techniques, discounts
      the biasing effect of single centre execution and gives insufficient weight to
      large and detailed observational studies. Unless these aspects are progressively
      included into systems for grading, evaluating and classifying evidence and duly
      empirically assessed (according to the EBM paradigm), the EBM process and
      movement will remain open to criticism of being more evidence-biased than
      evidence-based."All scientific work is incomplete--whether it be observational or
      experimental. All scientific work is liable to be upset or modified by advancing
      knowledge. That does not confer upon us a freedom to ignore the knowledge we
      already have, or to postpone the action that it appears to demand at a given
      time". (Sir Bradford Austin Hill 1).

PMID- 18826607
TI  - Phobic postural vertigo treated with autogenic training: a case report.
AB  - BACKGROUND: Patients suffering from dizziness due to vertigo are commonly
      encountered in the department of otolaryngology. If various clinical examinations
      do not reveal any objective findings, then the patients are referred to the
      department of internal medicine or psychiatry. In many cases, the diagnosis is
      psychological dizziness. Phobic postural vertigo, which was first reported by
      Brandt T et al in 1994, is supposed to be a type of psychological dizziness. The
      diagnosis is based on 6 characteristics proposed by Brandt et al. Patients are
      usually treated with conventional medical therapy, but some cases may be
      refractory to such a therapy. Psychotherapy is recommended in some cases;
      however, psychotherapy including autogenic training, which can be used for
      general relaxation, is not widely accepted. This paper describes the successful
      administration of autogenic training in a patient suffering from phobic postural
      vertigo. CASE PRESENTATION: We present a case of a patient who suffered from
      phobic postural vertigo. A 37-year-old female complained of dizziness. She had
      started experiencing dizziness almost 3 years She was intractable to many sort of
      conventional therapy. In the end, her symptom disappeared after introduction of
      autogenic training. CONCLUSION: Autogenic training can be a viable and acceptable
      treatment option for phobic postural vertigo patients who fail to respond to
      other therapies. This case emphasizes the importance of autogenic training as a
      method to control symptom of phobic postural vertigo.

PMID- 18826606
TI  - The effects of timing of fine needle aspiration biopsies on gene expression
      profiles in breast cancers.
AB  - BACKGROUND: DNA microarray analysis has great potential to become an important
      clinical tool to individualize prognostication and treatment for breast cancer
      patients. However, with any emerging technology, there are many variables one
      must consider before bringing the technology to the bedside. There are already
      concerted efforts to standardize protocols and to improve reproducibility of DNA
      microarray. Our study examines one variable that is often overlooked, the timing
      of tissue acquisition, which may have a significant impact on the outcomes of DNA
      microarray analyses especially in studies that compare microarray data based on
      biospecimens taken in vivo and ex vivo. METHODS: From 16 patients, we obtained
      paired fine needle aspiration biopsies (FNABs) of breast cancers taken before
      (PRE) and after (POST) their surgeries and compared the microarray data to
      determine the genes that were differentially expressed between the FNABs taken at
      the two time points. qRT-PCR was used to validate our findings. To examine
      effects of longer exposure to hypoxia on gene expression, we also compared the
      gene expression profiles of 10 breast cancers from clinical tissue bank. RESULTS:
      Using hierarchical clustering analysis, 12 genes were found to be differentially
      expressed between the FNABs taken before and after surgical removal. Remarkably,
      most of the genes were linked to FOS in an early hypoxia pathway. The gene
      expression of FOS also increased with longer exposure to hypoxia. CONCLUSION: Our
      study demonstrated that the timing of fine needle aspiration biopsies can be a
      confounding factor in microarray data analyses in breast cancer. We have shown
      that FOS-related genes, which have been implicated in early hypoxia as well as
      the development of breast cancers, were differentially expressed before and after
      surgery. Therefore, it is important that future studies take timing of tissue
      acquisition into account.

PMID- 18826608
TI  - Gene conversion and purifying selection of a placenta-specific ERV-V envelope
      gene during simian evolution.
AB  - BACKGROUND: Most human endogenous retroviruses (HERVs) invaded our genome at
      least 25 million years ago. The majority of the viral genes are degenerated,
      since no selection preserves them within the genome. However, a few intact and
      very old HERV genes exist, and likely are beneficial for the host. We here
      address evolutionary aspects of two HERV-V envelope genes, ENVV1 and ENVV2,
      located in tandem and containing a long open reading frame. RESULTS: The ENVV2
      gene is preserved with an intact reading frame during simian evolution, but none
      of the ENVV genes are found in the prosimian species tested. While we observe
      many transposon insertions in the gag and pol regions of the ERV-V2 provirus, the
      ENVV2 genes have escaped transposon crossfire in all species tested. Additional
      analysis of nucleotide substitutions provides further strong evidence of
      purifying selection on the ENVV2 gene during primate evolution. The other copy,
      ENVV1, seems to be involved in gene conversion of the major part of the envelope.
      Furthermore, ENVV1 and ENVV2 show placenta-specific expression in human and a
      baboon species. CONCLUSION: Our analyses show that ERV-V entered our genome after
      the split between simian and prosimian primates. Subsequent purifying selection
      and gene conversion have preserved two copies of the ENVV envelope gene in most
      species. This is the first case of gene conversion involving long open reading
      frames in HERVs. Together with the placenta-specific expression of the human and
      baboon ENVV1 and ENVV2 envelope genes, these data provide strong evidence of a
      beneficial role for the host.

PMID- 18826609
TI  - Seek, and ye shall find: accessing the global epidemiological literature in
      different languages.
AB  - The thematic series 'Beyond English: Accessing the global epidemiological
      literature' in Emerging Themes in Epidemiology highlights the wealth of
      epidemiological and public health literature in the major languages of the world,
      and the bibliographic databases through which they can be searched and accessed.
      This editorial suggests that all systematic reviews in epidemiology and public
      health should include literature published in the major languages of the world
      and that the use of regional and non-English bibliographic databases should
      become routine.

PMID- 18826610
TI  - DNA methylation changes in ovarian cancer are cumulative with disease progression
      and identify tumor stage.
AB  - BACKGROUND: Hypermethylation of promoter CpG islands with associated loss of gene
      expression, and hypomethylation of CpG-rich repetitive elements that may
      destabilize the genome are common events in most, if not all, epithelial cancers.
      METHODS: The methylation of 6,502 CpG-rich sequences spanning the genome was
      analyzed in 137 ovarian samples (ten normal, 23 low malignant potential, 18 stage
      I, 16 stage II, 54 stage III, and 16 stage IV) ranging from normal tissue through
      to stage IV cancer using a sequence-validated human CpG island microarray. The
      microarray contained 5' promoter-associated CpG islands as well as CpG-rich
      satellite and Alu repetitive elements. RESULTS: Results showed a progressive de
      evolution of normal CpG methylation patterns with disease progression; 659 CpG
      islands showed significant loss or gain of methylation. Satellite and Alu
      sequences were primarily associated with loss of methylation, while promoter CpG
      islands composed the majority of sequences with gains in methylation. Since the
      majority of ovarian tumors are late stage when diagnosed, we tested whether DNA
      methylation profiles could differentiate between normal and low malignant
      potential (LMP) compared to stage III ovarian samples. We developed a class
      predictor consisting of three CpG-rich sequences that was 100% sensitive and 89%
      specific when used to predict an independent set of normal and LMP samples versus
      stage III samples. Bisulfite sequencing confirmed the NKX-2-3 promoter CpG island
      was hypermethylated with disease progression. In addition, 5-aza-2'-deoxycytidine
      treatment of the ES2 and OVCAR ovarian cancer cell lines re-expressed NKX-2-3.
      Finally, we merged our CpG methylation results with previously published ovarian
      expression microarray data and identified correlated expression changes.
      CONCLUSION: Our results show that changes in CpG methylation are cumulative with
      ovarian cancer progression in a sequence-type dependent manner, and that CpG
      island microarrays can rapidly discover novel genes affected by CpG methylation
      in clinical samples of ovarian cancer.

PMID- 18826611
TI  - The relationship between depressive symptoms, health service consumption, and
      prognosis after acute myocardial infarction: a prospective cohort study.
AB  - BACKGROUND: The use of cardiovascular health services is greater among patients
      with depressive symptoms than among patients without. However, the extent to
      which such associations between depressive symptoms and health service
      utilization are attributable to variations in comorbidity and prognostic disease
      severity is unknown. This paper explores the relationship between depressive
      symptoms, health service cardiovascular consumption, and prognosis following
      acute myocardial infarction (AMI). METHODS: The study design was a prospective
      cohort study with follow-up telephone interviews of 1,941 patients 30 days
      following AMI discharged from 53 hospitals across Ontario, Canada between
      December 1999 and February, 2003. Outcome measures were post discharge use of
      cardiac and non-cardiac health care services. The service utilization outcomes
      were adjusted for age, sex, income, comorbidity, two validated measures of
      prognosis (cardiac functional capacity and risk adjustment severity index),
      cardiac procedures (CABG or PTCA) and drugs prescribed at discharge. RESULTS:
      Depressive symptoms were associated with a 24% (Adjusted RR:1.24; 95% CI:1.19
      1.30, P < 0.001), 9% (Adjusted RR:1.09; 95% CI:1.02-1.16, P = 0.007) and 43%
      (Adjusted RR: 1.43; 95% CI:1.34-1.52, P < 0.001) increase in total, cardiac, and
      non-cardiac hospitalization days post-AMI respectively, after adjusting for
      baseline patient and hospital characteristics. Depressive-associated increases in
      cardiac health service consumption were significantly more pronounced among
      patients of lower than higher cardiac risk severity. Depressive symptoms were not
      associated with increased mortality after adjusting for baseline patient
      characteristics. CONCLUSION: Depressive symptoms are associated with
      significantly higher cardiac and non-cardiac health service consumption following
      AMI despite adjustments for comorbidity and prognostic severity. The
      disproportionately higher cardiac health service consumption among lower-risk AMI
      depressive patients may suggest that health seeking behaviors are mediated by
      psychosocial factors more so than by objective measures of cardiovascular risk or
      necessity.

PMID- 18826612
TI  - Psychometric properties of Greek versions of the Modified Corah Dental Anxiety
      Scale (MDAS) and the Dental Fear Survey (DFS).
AB  - BACKGROUND: A growing body of literature describes the performance of dental fear
      questionnaires in various countries. We describe the psychometric properties of
      Greek versions of the Modified Dental Anxiety Scale (MDAS) and the Dental Fear
      Survey (DFS) in adult Greek patients. METHODS: Greek versions of the MDAS and DFS
      were administered to two samples of adult dental patients. In the first sample,
      195 patients attending one of three private practice dental offices in a large
      city in Greece completed the questionnaires in the waiting room before dental
      treatment. After treatment, their dentists (who did not know how the patients had
      answered the questionnaire) rated their anxiety during dental treatment. In the
      second sample, 41 patients attending a Greek university dental school clinic
      completed the questionnaire twice at two separate visits, in order to provide
      test-retest data. Cronbach's alpha was used to compute the internal
      consistencies, while Spearman's rho was used to compute the test-retest
      reliabilities. Construct validity was assessed by correlating the responses to
      the MDAS and DFS by Spearman's rho. Spearman's rho was also used to examine the
      criterion validities, by comparing the questionnaire responses with the dentists'
      ratings of anxiety. RESULTS: The internal consistencies for the MDAS were 0.90
      and 0.92 in the two samples; for the DFS, the internal consistencies were 0.96 in
      both samples. The test-retest reliabilities were 0.94 for the MDAS and 0.95 for
      the DFS. The correlation between the two questionnaires was 0.89. The patients'
      responses to both questionnaires were significantly related to the dentists'
      ratings of their anxiety during dental treatment (both p values <0.001).
      CONCLUSION: The results indicate that the Greek versions of the MDAS and DFS have
      good internal consistencies and test-retest reliabilities, as well as good
      construct and criterion validities. The psychometric properties of the Greek
      versions of these questionnaires appear to be similar to those previously
      reported in other countries.

PMID- 18826613
TI  - Posterior mediastinal melanoma causing severe dysphagia: a case report.
AB  - INTRODUCTION: We describe an original case of progressive severe dysphagia caused
      by a posterior mediastinal metastatic melanoma of unknown origin. To the best of
      our knowledge, such an event has never been described before in the literature.
      CASE PRESENTATION: A progressive severe dysphagia case is reported induced by a
      melanoma of unknown origin (metastatic to a posterior mediastinal lymph node). At
      the time of diagnosis, the lesion appeared as a large posterior mediastinal mass
      mimicking a neurogenic tumour with oesophageal involvement. After complete
      resection, pathological assessment of the tumour by immunohistochemistry was
      consistent with nodal metastatic melanoma. CONCLUSION: This report of a posterior
      mediastinal lymph node melanoma is unique. The nodal origin is definitely
      unusual: a primary melanoma should always be carefully ruled out. In fact no
      other evidence, a part from the absence of the tumour elsewhere, can support the
      diagnosis of a primary nodal melanoma.

PMID- 18826614
TI  - Small bowel perforation by a piece of china with a synchronous asymptomatic
      sigmoid carcinoma: A case report.
AB  - A 75 year old gentleman who presented with an incarcerated paraumibilical hernia
      was found intraoperatively to have small bowel perforation due to a piece of
      china with a synchronous asymptomatic sigmoid carcinoma.

PMID- 18826615
TI  - Giant inframuscular lipoma disclosed 14 years after a blunt trauma: a case
      report.
AB  - INTRODUCTION: Lipoma is the most frequent benign tumor of the soft tissue. This
      lesion is often asymptomatic except in cases of enormous masses compressing
      nervous-vascular structures. Although the diagnosis is mostly clinical, imaging
      tools are useful to confirm the adipose nature of the lesion and to define its
      anatomic border. Sometimes, lipomas may be the result of a previous trauma, such
      as in this patient. CASE PRESENTATION: A 45-year-old man presented at our
      institution with a giant hard firm mass in the upper external quadrant of the
      right buttock disclosed after a weight loss diet. Subsequent magnetic resonance
      imaging showed a giant adipose mass developed beneath the large gluteal muscle
      and among the fibers of the medium and small gluteal muscles. When questioned on
      his medical history, the patient reported a blunt trauma of the lower back 14
      years earlier. He underwent surgery and histological examination confirmed a
      giant lipoma. CONCLUSION: Lipomas might result from a previous trauma. It is
      hypothesized that the trigger mechanism is activated by cytokine and growth
      factors released after the trauma. We herein present an exceptional case of a
      giant post-traumatic lipoma which caused a painful compression on the right
      sciatic nerve.

PMID- 18826616
TI  - Mutational optimization of the coelenterazine-dependent luciferase from Renilla.
AB  - Renilla luciferase (RLUC) is a popular reporter enzyme for gene expression and
      biosensor applications, but it is an unstable enzyme whose catalytic mechanism
      remains to be elucidated. We titrated that one RLUC molecule can turn over about
      one hundred molecules of coelenterazine substrate. Mutagenesis of active site
      residue Pro220 extended the half-life of photon emission, yielding brighter
      luminescence in E. coli. Random mutagenesis uncovered two new mutations that
      stabilized and increased photon emission in vivo and in vitro, while ameliorating
      substrate inhibition. Further amended with a previously identified mutation, a
      new triple mutant showed a threefold improved kcat, as well as elevated
      luminescence in Arabidopsis. This advances the utility of RLUC as a reporter
      protein, biosensor, or resonance energy donor.

PMID- 18826617
TI  - Carbon fluxes resulting from land-use changes in the Tamaulipan thornscrub of
      northeastern Mexico.
AB  - Information on carbon stock and flux resulting from land-use changes in
      subtropical, semi-arid ecosystems are important to understand global carbon flux,
      yet little data is available. In the Tamaulipan thornscrub forests of
      northeastern Mexico, biomass components of standing vegetation were estimated
      from 56 quadrats (200 m2 each). Regional land-use changes and present forest
      cover, as well as estimates of soil organic carbon from chronosequences, were
      used to predict carbon stocks and fluxes in this ecosystem.For the period of 1980
      1996, the Tamaulipan thornscrub is presenting an annual deforestation rate of
      2.27% indicating that approximately 600 km2 of this plant community are lost
      every year and that 60% of the original Mexican Tamaulipan thornscrub vegetation
      has been lost since the 1950's. On the other hand, intensive agriculture,
      including introduced grasslands increased (4,000 km2) from 32 to 42% of the total
      studied area, largely at the expense of the Tamaulipan thornscrub forests. Land
      use changes from Tamaulipan thornscrub forest to agriculture contribute 2.2 Tg to
      current annual carbon emissions and standing biomass averages 0.24 +/- 0.06 Tg,
      root biomass averages 0.17 +/- 0.03 Tg, and soil organic carbon averages 1.80 +/-
      0.27 Tg. Land-use changes from 1950 to 2000 accounted for Carbon emissions of the
      order of 180.1 Tg. Projected land-use changes will likely contribute to an
      additional carbon flux of 98.0 Tg by the year 2100. Practices to conserve
      sequester, and transfer carbon stocks in semi-arid ecosystems are discussed as a
      means to reduce carbon flux from deforestation practices.

PMID- 18826618
TI  - Regulon organization of Arabidopsis.
AB  - BACKGROUND: Despite the mounting research on Arabidopsis transcriptome and the
      powerful tools to explore biology of this model plant, the organization of
      expression of Arabidopsis genome is only partially understood. Here, we create a
      coexpression network from a 22,746 Affymetrix probes dataset derived from 963
      microarray chips that query the transcriptome in response to a wide variety of
      environmentally, genetically, and developmentally induced perturbations. RESULTS:
      Markov chain graph clustering of the coexpression network delineates 998 regulons
      ranging from one to 1623 genes in size. To assess the significance of the
      clustering results, the statistical over-representation of GO terms is averaged
      over this set of regulons and compared to the analogous values for 100 randomly
      generated sets of clusters. The set of regulons derived from the experimental
      data scores significantly better than any of the randomly-generated sets. Most
      regulons correspond to identifiable biological processes and include a
      combination of genes encoding related developmental, metabolic pathway, and
      regulatory functions. In addition, nearly 3000 genes of unknown molecular
      function or process are assigned to a regulon. Only five regulons contain
      plastomic genes; four of these are exclusively plastomic. In contrast, expression
      of the mitochondrial genome is highly integrated with that of nuclear genes; each
      of the seven regulons containing mitochondrial genes also incorporates nuclear
      genes. The network of regulons reveals a higher-level organization, with dense
      local neighborhoods articulated for photosynthetic function, genetic information
      processing, and stress response. CONCLUSION: This analysis creates a framework
      for generation of experimentally testable hypotheses, gives insight into the
      concerted functions of Arabidopsis at the transcript level, and provides a test
      bed for comparative systems analysis.

PMID- 18826619
TI  - Measuring differentiation among populations at different levels of genetic
      integration.
AB  - BACKGROUND: Most genetic studies of population differentiation are based on gene
      pool frequencies. Population differences for gene associations that show up as
      deviations from Hardy-Weinberg proportions (homologous association) or gametic
      disequilibria (non-homologous association) are disregarded. Thus little is known
      about patterns of population differentiation at higher levels of genetic
      integration nor the causal forces. RESULTS: To fill this gap, a conceptual
      approach to the description and analysis of patterns of genetic differentiation
      at arbitrary levels of genetic integration (single or multiple loci, varying
      degrees of ploidy) is introduced. Measurement of differentiation is based on the
      measure Delta of genetic distance between populations, which is in turn based on
      an elementary genic difference between individuals at any given level of genetic
      integration. It is proven that Delta does not decrease when the level of genetic
      integration is increased, with equality if the gene associations at the higher
      level follow the same function in both populations (e.g. equal inbreeding
      coefficients, no association between loci). The pattern of differentiation is
      described using the matrix of pairwise genetic distances Delta and the
      differentiation snail based on the symmetric population differentiation DeltaSD.
      A measure of covariation compares patterns between levels. To show the
      significance of the observed differentiation among possible gene associations, a
      special permutation analysis is proposed. Applying this approach to published
      genetic data on oak, the differentiation is found to increase considerably from
      lower to higher levels of integration, revealing variation in the forms of gene
      association among populations. CONCLUSION: This new approach to the analysis of
      genetic differentiation among populations demonstrates that the consideration of
      gene associations within populations adds a new quality to studies on population
      differentiation that is overlooked when viewing only gene-pools.

PMID- 18826620
TI  - A patient with glycogen storage disease type Ib presenting with acute myeloid
      leukemia (AML) bearing monosomy 7 and translocation t(3;8)(q26;q24) after 14
      years of treatment with granulocyte colony-stimulating factor (G-CSF): a case
      report.
AB  - INTRODUCTION: Glycogen storage disease type Ib is an autosomal recessive
      transmitted disorder of glycogen metabolism caused by mutations in the glucose-6
      phosphate translocase gene on chromosome 11q23 and leads to disturbed
      glycogenolysis as well as gluconeogenesis. Besides hepatomegaly, growth
      retardation, hypoglycemia, hyperlactatemia, hyperuricemia and hyperlipidemia,
      patients suffer from neutropenia associated with functional defects predisposing
      for severe infections. In order to attenuate these complications, long-term
      treatment with granulocyte colony-stimulating factor is common but this is
      associated with an increased risk for acute myeloid leukemia or myelodysplastic
      syndromes in patients with inherited bone marrow failures such as severe
      congenital neutropenia. Onset of these myeloid malignancies is linked to
      cytogenetic aberrations involving chromosome 7. In addition, granulocyte colony
      stimulating factor is known to stimulate proliferation of monosomy 7 cells in
      vitro. To our knowledge, we report for the first time a case report of a patient
      with glycogen storage disease type Ib, who developed acute myeloid leukemia with
      a classical monosomy 7 and acute myeloid leukemia-associated translocation
      t(3;8)(q26;q24) after 14 years of continuous treatment with granulocyte colony
      stimulating factor. CASE PRESENTATION: A 28-year-old Turkish man with glycogen
      storage disease type Ib was admitted to our department because of dyspnea and
      increasing fatigue. He also presented with gum bleeding, bone pain in his legs,
      night sweats, recurrent episodes of fever with temperatures up to 39 degrees C
      and hepatosplenomegaly.A blood count taken on the day of admission showed
      pancytopenia and a differential count displayed 30% blasts. A bone marrow biopsy
      was taken which showed a hypercellular marrow with dysplastic features of all
      three cell lines, while blast count was 20%. Classical cytogenetic analyses as
      well as fluorescence in situ hybridization showed a monosomy 7 with a
      translocation t(3;8)(q26;q24). Based on these findings, the diagnosis of acute
      myeloid leukemia was made. CONCLUSION: Our observations suggest that bone marrow
      examinations including cytogenetic analysis should be carried out on a regular
      basis in patients with glycogen storage disease type Ib who are on long-term
      treatment with granulocyte colony-stimulating factor for severe neutropenia,
      since this treatment might also contribute to an increased risk for acute myeloid
      leukemia or myelodysplastic syndromes.

PMID- 18826621
TI  - Weight, height, body mass index and risk of breast cancer in postmenopausal
      women: a case-control study.
AB  - BACKGROUND: Many women in Iran have a relatively high body mass index. To
      investigate whether the condition contributes to excess breast cancer cases, a
      case-control study was conducted to assess the relationships between
      anthropometric variables and breast cancer risk in Tehran, Iran. METHODS: All
      incident cases of breast cancer in the Iranian Centre for Breast Cancer (ICBC)
      were identified through the case records. Eligible cases were all postmenopausal
      women with histological confirmed diagnosis of breast cancer during 1996 to year
      2000. Controls were randomly selected postmenopausal women attending the ICBC for
      clinical breast examination during the same period. The body mass index (BMI) was
      calculated based on weights and heights as measured by the ICBC nursing staff.
      Both tests for trend and logistic regression analysis were performed to calculate
      odds ratios and 95% confidence intervals as measures of relative risk. RESULTS:
      In all, 116 breast cancer cases and 116 controls were studied. There were no
      significant differences between cases and control with regard to most independent
      variables studied. However, a significant difference was observed between cases
      and controls indicating that the mean BMI was higher in cases as compared to
      controls (P = 0.004). Performing logistic regression analysis while controlling
      for age, age at menopause, family history of breast cancer and parity, the
      results showed that women with a BMI in the obese range had a three fold
      increased risk of breast cancer [odds ratio (OR) = 3.21, 95% confidence interval
      (CI): 1.15-8.47]. CONCLUSION: The results suggest that obesity in postmenopausal
      women could increase risk of breast cancer and it merits further investigation in
      populations such as Iran where it seems that many women are short in height, and
      have a relatively high body mass index.

PMID- 18826622
TI  - Segmental resection of the duodenum for gastrointestinal stromal tumor (GIST).
AB  - BACKGROUND: Gastrointestinal stromal tumors (GIST) are the most frequent
      mesenchymal tumors of the gastrointestinal tract. The biological appearance of
      these tumors reaches from small lesions with benign appearance to aggressive
      sarcomas. Only 3-5% of GISTs are localized in the duodenum. There is a
      controversy, if duodenal GISTs should be treated by a duodenopancreatectomy or by
      a limited resection of the duodenum. CASE PRESENTATION: A 29-year-old man
      presented with an acute upper gastrointestinal bleeding from a submucosal tumor
      located in the proximal part III of the duodenum, 3 cm distal of the papilla of
      Vater. After an emergency laparotomy with ligation of tumor-feeding vessels in a
      primary hospital, definitive surgical therapy was performed by partial resection
      of the duodenum with a duodenojejunostomy. Histology revealed a GIST with a
      diameter of 2.5 cm and <5 mitoses/50 high power fields, indicating a low risk of
      malignancy. Therefore no adjuvant therapy with Imatinib was initiated.
      CONCLUSION: GISTs of the duodenum are a rare cause of upper gastrointestinal
      bleeding. Partial resection of the duodenum is a warranted alternative to a
      duodenopancreatectomy, as this procedure has a lower operative morbidity, while
      providing comparable oncological results.

PMID- 18826623
TI  - Thermal burn of palate caused by microwave heated cheese-pie: A case report.
AB  - A female patient, 36-years-old, complained of bilateral palatal pain on the
      anatomical area of upper second molars. The painful condition of palatal mucosa
      erosion was observed. Palatal erosions or ulcerations may be caused by heated
      food cooked in microwave ovens. We present a case of a bilateral palatal burn
      caused by cheese-pie. Concluding, any food containing cheese, when heated in
      microwave oven, may cause palatal burn if eaten immediately.

PMID- 18826624
TI  - Decrease in excitatory neurons, astrocytes and proliferating progenitors in the
      cerebral cortex of mice lacking exon 3 from the Fgf2 gene.
AB  - BACKGROUND: The Fgf2 gene is expressed in the brain neuroepithelium during
      embryonic development and in astroglial cells throughout life. Previous knockout
      studies suggested that FGF2 plays a role in the proliferation of neural
      progenitors in the embryonic cerebral cortex. These studies exclusively used
      knockout alleles lacking the Fgf2 exon 1. However, the description of putative
      alternative exons located downstream from the canonical exon 1 raised the
      possibility that alternatively spliced transcripts may compensate for the lack of
      the canonical exon 1 in the Fgf2 -/- mice. RESULTS: We generated and
      characterized a new line of Fgf2 knockout mice lacking the expression of exon 3,
      which is conserved in all Fgf2 transcripts and contains essential heparin and
      receptor binding interfaces. The expression of Fgf2 exon 3 was prevented by
      inserting a transcriptional STOP cassette in the Fgf2 genomic locus. These mice
      demonstrate a phenotype in the adult neocortex characterized by decreased density
      and number of cortical excitatory neurons and astrocytes, which is virtually
      identical to that of the Fgf2 -/- mice lacking exon 1. In addition, we also show
      that the Fgf2 exon 3 knockout mice have decreased proliferation of precursors in
      the adult cerebral cortex, which had not been previously investigated in the
      other mutant lines. CONCLUSION: The results demonstrate that the phenotype of two
      completely different Fgf2 KO mouse lines, lacking exon 1 or exon 3, is remarkably
      similar. The combined results from these KO models clearly indicate that FGF2
      plays a role in cortical cell genesis during embryonic development as well as in
      adulthood. Thus, FGF2 may be required for the maintenance of the pool of adult
      cortical progenitor cells.

PMID- 18826625
TI  - A standard procedure for creating a frailty index.
AB  - BACKGROUND: Frailty can be measured in relation to the accumulation of deficits
      using a frailty index. A frailty index can be developed from most ageing
      databases. Our objective is to systematically describe a standard procedure for
      constructing a frailty index. METHODS: This is a secondary analysis of the Yale
      Precipitating Events Project cohort study, based in New Haven CT. Non-disabled
      people aged 70 years or older (n = 754) were enrolled and re-contacted every 18
      months. The database includes variables on function, cognition, co-morbidity,
      health attitudes and practices and physical performance measures. Data came from
      the baseline cohort and those available at the first 18-month follow-up
      assessment. RESULTS: Procedures for selecting health variables as candidate
      deficits were applied to yield 40 deficits. Recoding procedures were applied for
      categorical, ordinal and interval variables such that they could be mapped to the
      interval 0-1, where 0 = absence of a deficit, and 1= full expression of the
      deficit. These individual deficit scores were combined in an index, where 0= no
      deficit present, and 1= all 40 deficits present. The values of the index were
      well fit by a gamma distribution. Between the baseline and follow-up cohorts, the
      age-related slope of deficit accumulation increased from 0.020 (95% confidence
      interval, 0.014-0.026) to 0.026 (0.020-0.032). The 99% limit to deficit
      accumulation was 0.6 in the baseline cohort and 0.7 in the follow-up cohort.
      Multivariate Cox analysis showed the frailty index, age and sex to be significant
      predictors of mortality. CONCLUSION: A systematic process for creating a frailty
      index, which relates deficit accumulation to the individual risk of death, showed
      reproducible properties in the Yale Precipitating Events Project cohort study.
      This method of quantifying frailty can aid our understanding of frailty-related
      health characteristics in older adults.

PMID- 18826627
TI  - Emphysematous pyelonephritis in type II diabetes: A case report of an undiagnosed
      ureteric colic.
AB  - INTRODUCTION: Emphysematous pyelonephritis (EPN) is a severe acute necrotising
      infection of the renal parenchyma and perirenal tissue, characterised by gas
      formation. 90% of cases are seen in association with diabetes mellitus. We report
      a case of undiagnosed ureteric obstruction in a type II diabetic, leading to EPN
      requiring emergency nephrectomy. CASE PRESENTATION: A 59-year-old type II tablet
      controlled diabetic woman presented complaining of a five day history of right
      sided abdominal pain associated with vomiting, abdominal distension and absolute
      constipation. There were no lower urinary tract symptoms. Past surgical history
      included an open appendectomy and an abdominal hysterectomy. On examination, she
      was haemodynamically stable, the abdomen was soft, distended, and tender in the
      right upper and lower quadrants with no bowel sounds. Investigations revealed a
      CRP of 365 and 2+ blood and nitrite positive on the urine dipstick. The AXR was
      reported as normal on admission, however when reviewed in retrospect revealed the
      diagnosis. She was managed, therefore, as having adhesional bowel obstruction and
      a simple UTI. After four days, a CT was organised as she was not settling. This
      showed a right pyohydronephrosis with gas in the collecting system secondary to
      an 8 mm obstructing ureteric calculus. The kidney was drained percutaneously via
      a nephrostomy and the patient was commenced on a broad spectrum intravenous
      antibiotics. Despite this, she went on to need an emergency nephrectomy for
      uncontrolled severe sepsis. She was discharged in good health 15 days later.
      CONCLUSION: EPN carries a mortality of up to 40% with medical management alone.
      Early recognition of EPN in an obstructed kidney is essential to guide aggressive
      management, and in the presence of continued severe sepsis or organ dysfunction
      an urgent nephrectomy should be carried out. Diabetic patients who are known to
      have renal or ureteric calculi, whether symptomatic or not, should be considered
      for percutanous or ureteroscopic treatment. In the acute abdomen, the plain
      abdominal radiograph should always be viewed with respect to general surgical,
      vascular and urological differential diagnoses.

PMID- 18826626
TI  - Immunoaffinity purification and characterization of mitochondrial membrane-bound
      D-3-hydroxybutyrate dehydrogenase from Jaculus orientalis.
AB  - BACKGROUND: The interconversion of two important energy metabolites, 3
      hydroxybutyrate and acetoacetate (the major ketone bodies), is catalyzed by D-3
      hydroxybutyrate dehydrogenase (BDH1: EC 1.1.1.30), a NAD+-dependent enzyme. The
      eukaryotic enzyme is bound to the mitochondrial inner membrane and harbors a
      unique lecithin-dependent activity. Here, we report an advanced purification
      method of the mammalian BDH applied to the liver enzyme from jerboa (Jaculus
      orientalis), a hibernating rodent adapted to extreme diet and environmental
      conditions. RESULTS: Purifying BDH from jerboa liver overcomes its low specific
      activity in mitochondria for further biochemical characterization of the enzyme.
      This new procedure is based on the use of polyclonal antibodies raised against
      BDH from bacterial Pseudomonas aeruginosa. This study improves the procedure for
      purification of both soluble microbial and mammalian membrane-bound BDH. Even
      though the Jaculus orientalis genome has not yet been sequenced, for the first
      time a D-3-hydroxybutyrate dehydrogenase cDNA from jerboa was cloned and
      sequenced. CONCLUSION: This study applies immunoaffinity chromatography to purify
      BDH, the membrane-bound and lipid-dependent enzyme, as a 31 kDa single
      polypeptide chain. In addition, bacterial BDH isolation was achieved in a two
      step purification procedure, improving the knowledge of an enzyme involved in the
      lipid metabolism of a unique hibernating mammal. Sequence alignment revealed
      conserved putative amino acids for possible NAD+ interaction.

PMID- 18826628
TI  - Operative management of a subtrochanteric fracture in severe osteoporosis. a case
      report.
AB  - BACKGROUND: Fractures of the subtrochanteric region of the femur provide several
      challenges to the operating surgeon due to anatomic and biomechanical
      peculiarities inherent to this region. These challenges are compounded several
      times in a severely porotic bone. CASE PRESENTATION: We report a case with severe
      osteoporosis who sustained a subtrochanteric fracture and was managed with a
      Dynamic condylar screw DCS. Three years after the surgery the patient is pain
      free and has a full range of motion. CONCLUSION: This highlights the fact that
      the DCS provides a viable alternative in the management of fractures of the
      subtrochanteric region in severe osteoporosis. This advantage is particularly
      manifest in settings where the image intensifier is not easily available.

PMID- 18826629
TI  - Successful treatment of bilateral open calcaneal fractures with concomitant lower
      extremity injuries: A case report.
AB  - Open calcaneal fractures are high morbidity injuries and the risk of
      complications depends on the concomitant injuries, on the size and the position
      of the traumatic wound. A 53-year-old male patient with bilateral open calcaneal
      fractures and associated concomitant lower extremity injuries such as subtalar
      dislocation, talonavicular dislocation and open distal tibial metaphyseal
      fracture was immediately operated by percutaneous Kirschner wire fixation
      combined with external fixators. He was able to walk with full weight bearing
      without any assistance at the end of the first postoperative year. Early
      aggressive debridement and irrigation followed by fixation with percutaneous
      Kirschner wires and external fixator can supply bony alignment in open comminuted
      calcaneal fractures associated with concomitant lower extremity injuries and
      should be considered for the healthy and active patients before primary
      arthrodesis.

PMID- 18826630
TI  - Presentation and course of brain metastases from breast cancer in a paranoid
      schizophrenic patient: A case report.
AB  - CASE PRESENTATION: This is an unusual case where a 49-year old female patient
      with known schizophrenia, paranoid type and a history of early-stage breast
      cancer, which was treated more than 6 years earlier, attempted suicide. Computed
      tomography and magnetic resonance imaging after this incident revealed the
      presence of multiple brain metastases as the first symptomatic site of recurrent
      cancer. Further staging lead to the diagnosis of lung, hilar and mediastinal
      lymph node metastases and histology confirmed estrogen receptor-positive
      metastatic cancer. Treatment consisted of whole-brain radiotherapy and letrozole.
      Twenty-one months later, the patient is in continued partial remission.

PMID- 18826631
TI  - The effect of menopause and hysterectomy on systemic vascular endothelial growth
      factor in women undergoing surgery for breast cancer.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF) is a potent angiogenic
      cytokine produced physiologically by the uterus. Pathological secretion by
      tumours promotes growth and metastasis. High circulating VEGF levels potentially
      have a deleterious effect on breast cancer by promoting disease progression. The
      aims of this study were to investigate circulating VEGF levels in breast cancer
      patients and assess the effect of menopause or hysterectomy on systemic VEGF.
      METHODS: Patients undergoing primary surgery for breast cancer and controls
      matched for age, menopausal and hysterectomy status were prospectively recruited.
      Serum VEGF, FSH, LH, estrogen, progesterone and platelet levels were measured.
      Serum VEGF was corrected for platelet load (sVEGFp) to provide a biologically
      relevant measurement of circulating VEGF. SVEGFp levels were analyzed with
      respect to tumor characteristics, menopausal status and hysterectomy status.
      RESULTS: Two hundred women were included in the study; 89 breast cancer patients
      and 111 controls. SVEGFp levels were significantly higher in breast cancer
      patients compared to controls (p = 0.0001), but were not associated with clinico
      pathological tumor characteristics. Systemic VEGF levels reduced significantly in
      the breast cancer patients following tumor excision (p = 0.018). The highest
      systemic VEGF levels were observed in postmenopausal breast cancer patients.
      Postmenopausal women who had had a previous hysterectomy had significantly higher
      VEGF levels than those with an intact postmenopausal uterus (p = 0.001).
      CONCLUSION: This study identifies an intact postmenopausal uterus as a potential
      means of reducing circulating levels of VEGF which could confer a protective
      effect against breast cancer metastatic potential.

PMID- 18826632
TI  - Anesthetic management of a patient with prosthetic heart valve for non-cardiac
      surgery: A case report.
AB  - BACKGROUND: Patients with prosthetic heart valves are a challenge to any
      anesthesiologist due to the risk of infective endocarditis, bleeding and
      thrombosis. CASE PRESENTATION: We present anesthetic management of a 58-year-old
      Indian lady with a prosthetic (mechanical) heart valve who underwent
      hemireplacement arthroplasty. CONCLUSION: Patients with prosthetic heart valves,
      especially those with the mechanical valves are prone for thrombosis and
      resultant complications if anticoagulation is not maintained properly. However,
      when they are scheduled for major surgery, they can be best managed by
      normalising the coagulation profile immediately prior to surgery and restarting
      the anticoagulation as early as possible.

PMID- 18826633
TI  - Large duodenal GIST with massive liver secondaries melting under Imatinib: a case
      report.
AB  - Gastrointestinal stromal tumors(GIST) have become a well established entity and
      its taxonomy is no more ambiguous. Better understanding of the cell of origin and
      immunohistochmical markers have made this possible. Their treatment has been
      revolutionized with the advent of targeted molecular therapy, namely Imatinib
      mesylate. Herein we report a rare and interesting case of a thirty year old South
      Indian Lady with an extremely large Duodenal GIST with massive Liver secondaries.
      The phenomenon of metastatic GIST responding to Imatinib mesylate is not new.
      What is interesting in this case is the enormous tumor load at the time of
      presentation as exemplified by the cross sectional images. This kind of tumor
      response and patient survival deserves documentation.

PMID- 18826634
TI  - Severe adult ileosigmoid intussusception prolapsing from the rectum: A case
      report.
AB  - Intussusception is a pediatric condition that rarely presents in adults. In this
      article, we report a case of a 36 year-old man initially presenting with
      abdominal pain and rectal prolapse, however, surgical reduction of the rectal
      prolapse did no relief his symptoms. Physical examination, abdominal plain film,
      barium enema and colonoscopy confirmed the presence of a large intra-abdominal
      mass, but the origin of the mass was revealed only upon laparotomy. During the
      surgery, it was noted that the ileum and the sigmoid colon was connected by a 15
      cm x 12cm mass, covered by an extremely dilated intestinal tissue. The resected
      tissue pathology demonstrated a 9 cm x 6 cm x 5 cm submucosal lipoma at the
      ileocecal junction without evidence of malignancy. The patient's post-surgical
      course was uneventful. Diagnostic and therapeutic problems related to adult
      intussusception are reviewed.

PMID- 18826635
TI  - End-digits preference for self-reported height depends on language.
AB  - BACKGROUND: When individuals report figures, they often prefer to round to
      specific end-digits (e.g. zero). Such preference has been found in reports of
      body weight, cigarette consumption or blood pressure measurements. Very little is
      known about self-reported body height. End-digit preference can distort estimates
      of prevalence and other statistical parameters. This study examines end-digit
      preference for self-reported height and how it relates with sex, age, educational
      level or cultural affiliation. METHODS: We analysed reports of height of 47,192
      individuals (aged 15 years or older) living in Switzerland and participating in
      one of the three population-based Swiss Health Surveys carried out in 1992/93,
      1997 and 2002 respectively. Digit preferences were analysed by sex, age group,
      educational level, survey, smoking status, interview language (only for Swiss
      nationals) and nationality. Adjusted odds ratios (OR) with 95% confidence
      interval were calculated by using multivariate logistic regression. RESULTS:
      Italian and French nationals (44.1% and 40.6%) and Italian and French Swiss
      (39.6% and 35.3%) more strongly preferred zero and five than Germans and German
      Swiss (29.2% and 30.3%). Two, four, six and eight were more popular in Germans
      and German Swiss (both 44.4%). Compared to German Swiss (OR = 1), for the end
      digits zero and five, the OR were 1.50 (1.38-1.63) for Italian Swiss and 1.24
      (1.18-1.30) for French Swiss; 1.73 (1.58-1.89) for Italian nationals and 1.61
      (1.33-1.95) for French nationals. The end-digits two, four, six and eight showed
      an opposite pattern. CONCLUSION: Different preferences for end-digits depending
      on language and nationality could be observed consistently in all three national
      health surveys. The patterns were strikingly similar in Swiss and foreign
      nationals speaking the same language, suggesting that preferences were specific
      to language rather than to nationality. Taking into account rounding preferences
      could allow more valid comparisons in analyses of self-reported data originating
      from different cultures.

PMID- 18826636
TI  - Users' guides to the medical literature: how to use an article about mortality in
      a humanitarian emergency.
AB  - The accurate interpretation of mortality surveys in humanitarian crises is useful
      for both public health responses and security responses. Recent examples suggest
      that few medical personnel and researchers can accurately interpret the validity
      of a mortality survey in these settings. Using an example of a mortality survey
      from the Democratic Republic of Congo (DRC), we demonstrate important
      methodological considerations that readers should keep in mind when reading a
      mortality survey to determine the validity of the study and the applicability of
      the findings to their settings.

PMID- 18826637
TI  - Evaluation of the quality of informed consent in a vaccine field trial in a
      developing country setting.
AB  - BACKGROUND: Informed consent is an ethical and legal requirement for research
      involving human participants. However, few studies have evaluated the process,
      particularly in Africa. Participants in a case control study designed to identify
      correlates of immune protection against tuberculosis (TB) in South Africa. This
      study was in turn nested in a large TB vaccine efficacy trial. The aim of the
      study was to evaluate the quality of consent in the case control study, and to
      identify factors that may influence the quality of consent. Cross-sectional study
      conducted over a 4 month period. METHODS: Consent was obtained from parents of
      trial participants. These parents were asked to complete a questionnaire that
      contained questions about the key elements of informed consent (voluntary
      participation, confidentiality, the main risks and benefits, etc.). The recall
      (success in selecting the correct answers) and understanding (correctness of
      interpretation of statements presented) were measured. RESULTS: The majority of
      the 192 subjects interviewed obtained scores greater than 75% for both the recall
      and understanding sections. The median score for recall was 66%; interquartile
      range (IQR) = 55%-77% and for understanding 75% (IQR = 50%-87%). Most (79%) were
      aware of the risks and 64% knew that they participated voluntarily. Participants
      who had completed Grade 7 at school and higher were more likely (OR = 4.94; 95%
      CI = 1.57 - 15.55) to obtain scores greater than 75% for recall than those who
      did not. Participants who were consented by professional nurses who had worked
      for more than two years in research were also more likely (OR = 2.62; 95% CI =
      1.35-5.07) to obtain such scores for recall than those who were not. CONCLUSION:
      Notwithstanding the constraints in a developing country, in a population with low
      levels of literacy and education, the quality of informed consent found in this
      study could be considered as building blocks for establishing acceptable
      standards for public health research. Education level of respondents and
      experience of research staff taking the consent were associated with good quality
      informed consent.

PMID- 18826638
TI  - Epitope spreading to citrullinated antigens in mouse models of autoimmune
      arthritis and demyelination.
AB  - INTRODUCTION: Anti-citrullinated protein antibodies have a diagnostic role in
      rheumatoid arthritis (RA); however, little is known about their origins and
      contribution to pathogenesis. Citrullination is the post-translational conversion
      of arginine to citrulline by peptidyl arginine deiminase, and increased
      citrullination of proteins is observed in the joint tissue in RA and in brain
      tissue in multiple sclerosis (MS). METHODS: We applied synovial and myelin
      protein arrays to examine epitope spreading of B cell responses to citrullinated
      epitopes in both the collagen-induced arthritis (CIA) model for RA and the
      experimental autoimmune encephalomyelitis (EAE) model for MS. Synovial and myelin
      protein arrays contain a spectrum of proteins and peptides, including native and
      citrullinated forms, representing candidate autoantigens in RA and MS,
      respectively. We applied these arrays to characterise the specificity of
      autoantibodies in serial serum samples derived from mice with acute and chronic
      stages of CIA and EAE. RESULTS: In samples from pre-disease CIA and acute-disease
      EAE, we observed autoantibody targeting of the immunising antigen and responses
      to a limited set of citrullinated epitopes. Over the course of diseases, the
      autoantibody responses expanded to target multiple citrullinated epitopes in both
      CIA and EAE. Using immunoblotting and mass spectrometry analysis, we identified
      citrullination of multiple polypeptides in CIA joint and EAE brain tissue that
      have not previously been described as citrullinated. CONCLUSIONS: Our results
      suggest that anti-citrulline antibody responses develop in the early stages of
      CIA and EAE, and that autoimmune inflammation results in citrullination of joint
      proteins in CIA and brain proteins in EAE, thereby creating neoantigens that
      become additional targets in epitope spreading of autoimmune responses.

PMID- 18826639
TI  - A quantitative PCR method to detect blood microRNAs associated with tumorigenesis
      in transgenic mice.
AB  - MicroRNA (miRNA) dysregulation frequently occurs in cancer. Analysis of whole
      blood miRNA in tumor models has not been widely reported, but could potentially
      lead to novel assays for early detection and monitoring of cancer. To determine
      whether miRNAs associated with malignancy could be detected in the peripheral
      blood, we used real-time reverse transcriptase-PCR to determine miRNA profiles in
      whole blood obtained from transgenic mice with c-MYC-induced lymphoma,
      hepatocellular carcinoma and osteosarcoma. The PCR-based assays used in our
      studies require only 10 nanograms of total RNA, allowing serial mini-profiles (20
      - 30 miRNAs) to be carried out on individual animals over time. Blood miRNAs were
      measured from mice at different stages of MYC-induced lymphomagenesis and
      regression. Unsupervised hierarchical clustering of the data identified specific
      miRNA expression profiles that correlated with tumor type and stage. The miRNAs
      found to be altered in the blood of mice with tumors frequently reverted to
      normal levels upon tumor regression. Our results suggest that specific changes in
      blood miRNA can be detected during tumorigenesis and tumor regression.

PMID- 18826640
TI  - Abdominal compartment syndrome post-late Bochdalek hernia repair: A case report.
AB  - The aim of this case report is to discuss the rare postoperative complication of
      abdominal compartment syndrome in a 19-year-old Caucasian Greek male that was
      electively operated on for a congenital diaphragmatic hernia. The hernia was
      completely asymptomatic and was found in chest radiography for employment
      reasons. Abdominal compartment syndrome is related in most reports with trauma
      and abdominal operations. Timely diagnosis is key to the prevention of further
      organ damage and multisystem organ dysfunction because the syndrome once
      instituted is highly fatal.

PMID- 18826641
TI  - Molecular and macromolecular alterations of recombinant adenoviral vectors do not
      resolve changes in hepatic drug metabolism during infection.
AB  - In this report we test the hypothesis that long-term virus-induced alterations in
      CYP occur from changes initiated by the virus that may not be related to the
      immune response. Enzyme activity, protein expression and mRNA of CYP3A2, a
      correlate of human CYP3A4, and CYP2C11, responsive to inflammatory mediators,
      were assessed 0.25, 1, 4, and 14 days after administration of several different
      recombinant adenoviruses at a dose of 5.7 x 1012 virus particles (vp)/kg to male
      Sprague Dawley rats. Wild type adenovirus, containing all viral genes, suppressed
      CYP3A2 and 2C11 activity by 37% and 39%, respectively within six hours. Levels
      fell to 67% (CYP3A2) and 79% (CYP2C11) of control by 14 days (p <or= 0.01).
      Helper-dependent adenovirus, with all viral genes removed, suppressed CYP3A2
      (43%) and CYP2C11 (55%) within six hours. CYP3A2 remained significantly
      suppressed (47%, 14 days, p <or= 0.01) while CYP2C11 returned to baseline at this
      time. CYP3A2 and 2C11 were reduced by 45 and 42% respectively 6 hours after
      treatment with PEGylated adenovirus, which has a low immunological profile (p
      <or= 0.05). CYP3A2 remained suppressed (34%, p <or= 0.05) for 14 days while
      CYP2C11 recovered. Inactivated virus suppressed CYP3A2 activity by 25-50% for 14
      days (p <or= 0.05). CYP2C11 was affected similar manner but recovered by day 14.
      Microarray and in vitro studies suggest that changes in cellular signaling
      pathways initiated early in virus infection contribute to changes in CYP.

PMID- 18826642
TI  - Transverse testicular ectopia associated with incarcerated inguinal hernia: a
      case report.
AB  - Transverse testicular ectopia is rarely associated with incarcerated inguinal
      hernia. A 14-month-old male complaint of irreducible inguinal hernia due to
      transverse testicular ectopia is reported. The clinical and operative findings
      and treatment options are discussed. It is thought that surgeons who frequently
      repair inguinal hernias should be aware of the appropriate surgical management
      options available to them when this condition is unexpectedly identified during
      inguinal exploration.

PMID- 18826643
TI  - Evidence for Hox-specified positional identities in adult vasculature.
AB  - BACKGROUND: The concept of specifying positional information in the adult
      cardiovascular system is largely unexplored. While the Hox transcriptional
      regulators have to be viewed as excellent candidates for assuming such a role,
      little is known about their presumptive cardiovascular control functions and in
      vivo expression patterns. RESULTS: We demonstrate that conventional reporter gene
      analysis in transgenic mice is a useful approach for defining highly complex Hox
      expression patterns in the adult vascular network as exemplified by our lacZ
      reporter gene models for Hoxa3 and Hoxc11. These mice revealed expression in
      subsets of vascular smooth muscle cells (VSMCs) and endothelial cells (ECs)
      located in distinct regions of the vasculature that roughly correspond to the
      embryonic expression domains of the two genes. These reporter gene patterns were
      validated as authentic indicators of endogenous gene expression by immunolabeling
      and PCR analysis. Furthermore, we show that persistent reporter gene expression
      in cultured cells derived from vessel explants facilitates in vitro
      characterization of phenotypic properties as exemplified by the differential
      response of Hoxc11-lacZ-positive versus-negative cells in migration assays and to
      serum. CONCLUSION: The data support a conceptual model of Hox-specified
      positional identities in adult blood vessels, which is of likely relevance for
      understanding the mechanisms underlying regional physiological diversities in the
      cardiovascular system. The data also demonstrate that conventional Hox reporter
      gene mice are useful tools for visualizing complex Hox expression patterns in the
      vascular network that might be unattainable otherwise. Finally, these mice are a
      resource for the isolation and phenotypic characterization of specific
      subpopulations of vascular cells marked by distinct Hox expression profiles.

PMID- 18826644
TI  - An efficient method for visualization and growth of fluorescent Xanthomonas
      oryzae pv. oryzae in planta.
AB  - BACKGROUND: Xanthomonas oryzae pv. oryzae, the causal agent of bacterial blight
      disease, is a serious pathogen of rice. Here we describe a fluorescent marker
      system to study virulence and pathogenicity of X. oryzae pv. oryzae. RESULTS: A
      fluorescent X. oryzae pv. oryzae Philippine race 6 strain expressing green
      fluorescent protein (GFP) (PXO99GFP) was generated using the gfp gene under the
      control of the neomycin promoter in the vector, pPneo-gfp. The PXO99GFPstrain
      displayed identical virulence and avirulence properties as the wild type control
      strain, PXO99. Using fluorescent microscopy, bacterial multiplication and
      colonization were directly observed in rice xylem vessels. Accurate and rapid
      determination of bacterial growth was assessed using fluoremetry and an Enzyme
      Linked ImmunoSorbant Assay (ELISA). CONCLUSION: Our results indicate that the
      fluorescent marker system is useful for assessing bacterial infection and
      monitoring bacterial multiplication in planta.

PMID- 18826645
TI  - Prebiotic replicase evolution in a surface-bound metabolic system: parasites as a
      source of adaptive evolution.
AB  - BACKGROUND: The remarkable potential of recent forms of life for reliably passing
      on genetic information through many generations now depends on the coordinated
      action of thousands of specialized biochemical "machines" (enzymes) that were
      obviously absent in prebiotic times. Thus the question how a complicated system
      like the living cell could have assembled on Earth seems puzzling. In seeking for
      a scientific explanation one has to search for step-by-step evolutionary changes
      from prebiotic chemistry to the emergence of the first proto-cell. RESULTS: We
      try to sketch a plausible scenario for the first steps of prebiotic evolution by
      exploring the ecological feasibility of a mineral surface-bound replicator system
      that facilitates a primitive metabolism. Metabolism is a hypothetical network of
      simple chemical reactions producing monomers for the template-copying of RNA-like
      replicators, which in turn catalyse metabolic reactions. Using stochastic
      cellular automata (SCA) simulations we show that the surface-bound metabolic
      replicator system is viable despite internal competition among the genes and that
      it also maintains a set of mild "parasitic" sequences which occasionally evolve
      functions such as that of a replicase. CONCLUSION: Replicase activity is shown to
      increase even at the expense of slowing down the replication of the evolving
      ribozyme itself, due to indirect mutualistic benefits in a diffuse form of group
      selection among neighbouring replicators. We suggest possible paths for further
      evolutionary changes in the metabolic replicator system leading to increased
      metabolic efficiency, improved replicase functionality, and membrane production.

PMID- 18826646
TI  - Physician attitude toward depression care interventions: implications for
      implementation of quality improvement initiatives.
AB  - BACKGROUND: Few individuals with depression treated in the primary care setting
      receive care consistent with clinical treatment guidelines. Interventions based
      on the chronic care model (CCM) have been promoted to address barriers and
      improve the quality of care. A current understanding of barriers to depression
      care and an awareness of whether physicians believe interventions effectively
      address those barriers is needed to enhance the success of future implementation.
      METHODS: We conducted semi-structured interviews with 23 primary care physicians
      across the US regarding their experience treating patients with depression,
      barriers to care, and commonly promoted CCM-based interventions. Themes were
      identified from interview transcripts using a grounded theory approach. RESULTS:
      Six barriers emerged from the interviews: difficulty diagnosing depression,
      patient resistance, fragmented mental health system, insurance coverage, lack of
      expertise, and competing demands and other responsibilities as a primary care
      provider. A number of interventions were seen as helpful in addressing these
      barriers - including care managers, mental health integration, and education -
      while others received mixed reviews. Mental health consultation models received
      the least endorsement. Two systems-related barriers, the fragmented mental health
      system and insurance coverage limitations, appeared incompletely addressed by the
      interventions. CONCLUSION: CCM-based interventions, which include care managers,
      mental health integration, and patient education, are most likely to be
      implemented successfully because they effectively address several important
      barriers to care and are endorsed by physicians. Practices considering the
      adoption of interventions that received less support should educate physicians
      about the benefit of the interventions and attend to physician concerns prior to
      implementation. A focus on interventions that address systems-related barriers is
      needed to overcome all barriers to care.

PMID- 18826647
TI  - Cetuximab in the treatment of metastatic mucoepidermoid carcinoma of the salivary
      glands: a case report and review of literature.
AB  - INTRODUCTION: Patients with metastatic mucoepidermoid carcinoma of salivary
      glands have a poor outcome. The epidermal growth factor receptor protein is
      overexpressed in approximately 70% of mucoepidermoid carcinoma patients and may
      represent a therapeutic target. However, whether treatment with anti-epidermal
      growth factor receptor agents is effective is unclear and clinical trials are
      difficult due to the rarity of the disease. Here we assessed the activity of
      cetuximab in mucoepidermoid carcinoma on a molecular basis. CASE PRESENTATION: We
      present the case of a 40-year old Caucasian man with a mucoepidermoid carcinoma
      of the major salivary glands who developed distant bone and visceral metastases
      despite platinum-based chemotherapy. Epidermal growth factor receptor was
      overexpressed and fluorescence in situ hybridization analysis demonstrated a
      chromosome 7 polysomy. The patient was treated with the monoclonal antibody
      cetuximab in combination with cisplatin. After 11 doses of cetuximab, the patient
      developed brain metastases but evidence of response was documented at all
      extracranial metastatic sites. CONCLUSION: This case report indicates that
      cetuximab can be active in mucoepidermoid carcinoma and may restore sensitivity
      to cisplatin in platinum-treated patients. Cetuximab does not cross the blood
      brain barrier and may select a metastatic clone to home the central nervous
      system while responding at other sites.

PMID- 18826648
TI  - Musashi1 modulates cell proliferation genes in the medulloblastoma cell line
      Daoy.
AB  - BACKGROUND: Musashi1 (Msi1) is an RNA binding protein with a central role during
      nervous system development and stem cell maintenance. High levels of Msi1 have
      been reported in several malignancies including brain tumors thereby associating
      Msi1 and cancer. METHODS: We used the human medulloblastoma cell line Daoy as
      model system in this study to knock down the expression of Msi1 and determine the
      effects upon soft agar growth and neurophere formation. Quantitative RT-PCR was
      conducted to evaluate the expression of cell proliferation, differentiation and
      survival genes in Msi1 depleted Daoy cells. RESULTS: We observed that MSI1
      expression was elevated in Daoy cells cultured as neurospheres compared to those
      grown as monolayer. These data indicated that Msi1 might be involved in
      regulating proliferation in cancer cells. Here we show that shRNA mediated Msi1
      depletion in Daoy cells notably impaired their ability to form colonies in soft
      agar and to grow as neurospheres in culture. Moreover, differential expression of
      a group of Notch, Hedgehog and Wnt pathway related genes including MYCN, FOS,
      NOTCH2, SMO, CDKN1A, CCND2, CCND1, and DKK1, was also found in the Msi1
      knockdown, demonstrating that Msi1 modulated the expression of a subset of cell
      proliferation, differentiation and survival genes in Daoy. CONCLUSION: Our data
      suggested that Msi1 may promote cancer cell proliferation and survival as its
      loss seems to have a detrimental effect in the maintenance of medulloblastoma
      cancer cells. In this regard, Msi1 might be a positive regulator of tumor
      progression and a potential target for therapy.

PMID- 18826649
TI  - Linkage disequilibrium compared between five populations of domestic sheep.
AB  - BACKGROUND: The success of genome-wide scans depends on the strength and
      magnitude of linkage disequilibrium (LD) present within the populations under
      investigation. High density SNP arrays are currently in development for the sheep
      genome, however little is known about the behaviour of LD in this livestock
      species. This study examined the behaviour of LD within five sheep populations
      using two LD metrics, D' and x2'. Four economically important Australian sheep
      flocks, three pure breeds (White Faced Suffolk, Poll Dorset, Merino) and a
      crossbred population (Merino x Border Leicester), along with an inbred Australian
      Merino museum flock were analysed. RESULTS: Short range LD (0 - 5 cM) was
      observed in all five populations, however the persistence with increasing
      distance and magnitude of LD varied considerably between populations. Average LD
      (x2') for markers spaced up to 20 cM exceeded the non-syntenic average within the
      White Faced Suffolk, Poll Dorset and Macarthur Merino. LD decayed faster within
      the Merino and Merino x Border Leicester, with LD below or consistent with
      observed background levels. Using marker-marker LD as a guide to the behaviour of
      marker-QTL LD, estimates of minimum marker spacing were made. For a 95%
      probability of detecting QTL, a microsatellite marker would be required every 0.1
      - 2.5 centimorgans, depending on the population used. CONCLUSION: Sheep
      populations were selected which were inbred (Macarthur Merino), highly
      heterogeneous (Merino) or intermediate between these two extremes. This
      facilitated analysis and comparison of LD (x2') between populations. The strength
      and magnitude of LD was found to differ markedly between breeds and aligned
      closely with both observed levels of genetic diversity and expectations based on
      breed history. This confirmed that breed specific information is likely to be
      important for genome wide selection and during the design of successful genome
      scans where tens of thousands of markers will be required.

PMID- 18826650
TI  - Development of a food allergy education resource for primary care physicians.
AB  - BACKGROUND: Food allergy is estimated to affect 3-4% of adults in the US, but
      there are limited educational resources for primary care physicians. The goal of
      this study was to develop and pilot a food allergy educational resource based
      upon a needs survey of non-allergist healthcare providers. METHODS: A survey was
      undertaken to identify educational needs and preferences for providers, with a
      focus on physicians caring for adults and teenagers, including emergency medicine
      providers. The results of the survey were used to develop a teaching program that
      was subsequently piloted on primary care and emergency medicine physicians.
      Knowledge base tests and satisfaction surveys were administered to determine the
      effectiveness of the educational program. RESULTS: Eighty-two physicians
      (response rate, 65%) completed the needs assessment survey. Areas of deficiency
      and educational needs identified included: identification of potentially life
      threatening food allergies, food allergy diagnosis, and education of patients
      about treatment (food avoidance and epinephrine use). Small group, on-site
      training was the most requested mode of education. A slide set and narrative were
      developed to address the identified needs. Twenty-six separately enrolled
      participants were administered the teaching set. Pre-post knowledge base scores
      increased from a mean of 38% correct to 64% correct (p < 0.001). Ability to
      correctly demonstrate the use of epinephrine self injectors increased
      significantly. Nearly all participants (>95%) indicated that the teaching module
      increased their comfort with recognition and management of food allergy.
      CONCLUSION: Our pilot food allergy program, developed based upon needs
      assessments, showed strong participant satisfaction and educational value.

PMID- 18826651
TI  - Deaf-1 regulates epithelial cell proliferation and side-branching in the mammary
      gland.
AB  - BACKGROUND: The transcription factor DEAF-1 has been identified as a high
      affinity binding partner of the LIM-only protein LMO4 that plays important roles
      in mammary gland development and breast cancer. Here we investigated the
      influence of DEAF-1 on human and mouse mammary epithelial cells both in vitro and
      in vivo and identified a potential target gene. RESULTS: Overexpression of DEAF-1
      in human breast epithelial MCF10A cells enhanced cell proliferation in the
      mammary acini that develop in 3D cultures. To investigate the effects of Deaf-1
      on mammary gland development and oncogenesis, we generated MMTV-Deaf-1 transgenic
      mice. Increased ductal side-branching was observed in young virgin mammary
      glands, accompanied by augmented cell proliferation. In addition, the ratio of
      the progesterone receptor isoforms PRA and PRB, previously implicated in
      regulating ductal side-branching, was altered. Affymetrix gene profiling studies
      revealed Rac3 as a potential target gene and quantitative RT-PCR analysis
      confirmed that Rac3 was upregulated by Deaf-1 in immortalized mouse mammary
      epithelial cells. Furthermore, MMTV-Deaf-1 transgenic mammary glands were found
      to have elevated levels of Rac3 mRNA, suggesting that it is a bona fide target.
      CONCLUSION: We have demonstrated that overexpression of Deaf-1 enhances the
      proliferation of human breast epithelial cells in vitro and mouse epithelial
      cells in vivo. Transgenic mammary glands overexpressing Deaf-1 exhibited a modest
      side-branching phenotype, accompanied by an increase in the number of BrdU
      positive cells and a decrease in the proportion of PRA-expressing cells. Although
      proliferation was enhanced in Deaf-1 transgenic mice, overexpression of this gene
      was not sufficient to induce the formation of mammary tumors. In addition, our
      studies identified Rac3, encoding a small Rho-like GTPase, as a potential target
      of Deaf-1 in mouse mammary epithelial cells.

PMID- 18826652
TI  - Rhythm generation by the pre-Botzinger complex in medullary slice and island
      preparations: effects of adenosine A(1) receptor activation.
AB  - BACKGROUND: The pre-Botzinger complex (preBotC) is a central pattern generator
      within the ventrolateral medulla oblongata's ventral respiratory group that is
      important for the generation of respiratory rhythm. Activation of adenosine A(1)
      receptors (A(1)R) depresses preBotC rhythmogenesis. Although it remains unclear
      whether A(1)R activation is important for organisms in a normal metabolic state,
      A(1)R activation is important to the response of the preBotC to metabolic stress,
      such as hypoxia. This study examined mechanisms linking A(1)R activation to
      depression of preBotC rhythmogenesis in medullary slice and island preparations
      from neonatal mice. RESULTS: Converting medullary slices to islands by cutting
      away much of the medullary tissue adjacent to the preBotC decreased the amplitude
      of action potential bursts generated by a population of neurons within the
      preBotC (recorded with an extracellular electrode, and integrated using a
      hardware integrator), without noticeably affecting burst frequency. The A(1)R
      agonist N6-Cyclopentyladenosine (NCPA) reduced population burst frequency in
      slices by ca. 33% and in islands by ca. 30%. As in normal (drug-free) artificial
      cerebrospinal fluid (aCSF), NCPA decreased burst frequency in slices when
      GABA(A)ergic or GABA(A)ergic and glycinergic transmission were blocked, and in
      islands when GABA(A)ergic transmission was antagonized. Converting slices to
      island preparations decreased synaptic input to inspiratory neurons. NCPA further
      decreased the frequency of synaptic inputs to neurons in island preparations and
      lowered the input resistance of inspiratory neurons, even when chemical
      communication between neurons and other cells was impeded. CONCLUSION: Together
      these data support the suggestion that depression of preBotC activity by A(1)R
      activation involves both decreased neuronal excitability and diminished inter
      neuronal communication.

PMID- 18826653
TI  - Direct activation of transient receptor potential vanilloid 1(TRPV1) by
      diacylglycerol (DAG).
AB  - The capsaicin receptor, known as transient receptor potential channel vanilloid
      subtype 1 (TRPV1), is activated by a wide range of noxious stimulants and
      putative ligands such as capsaicin, heat, pH, anandamide, and phosphorylation by
      protein kinase C (PKC). However, the identity of endogenous activators for TRPV1
      under physiological condition is still debated. Here, we report that
      diacylglycerol (DAG) directly activates TRPV1 channel in a membrane-delimited
      manner in rat dorsal root ganglion (DRG) neurons. 1-oleoyl-2-acetyl-sn-glycerol
      (OAG), a membrane-permeable DAG analog, elicited intracellular Ca2+ transients,
      cationic currents and cobalt uptake that were blocked by TRPV1-selective
      antagonists, but not by inhibitors of PKC and DAG lipase in rat DRG neurons or
      HEK 293 cells heterologously expressing TRPV1. OAG induced responses were about
      one fifth of capsaicin induced signals, suggesting that OAG displays partial
      agonism. We also found that endogenously produced DAG can activate rat TRPV1
      channels. Mutagenesis of rat TRPV1 revealed that DAG-binding site is at Y511, the
      same site for capsaicin binding, and PtdIns(4,5)P2binding site may not be
      critical for the activation of rat TRPV1 by DAG in heterologous system. We
      propose that DAG serves as an endogenous ligand for rat TRPV1, acting as an
      integrator of Gq/11-coupled receptors and receptor tyrosine kinases that are
      linked to phospholipase C.

PMID- 18826654
TI  - Hematopoietic progenitor cells and interleukin-stimulated endothelium: expansion
      and differentiation of myeloid precursors.
AB  - BACKGROUND: Cytokine-stimulated endothelial cells (EC) propagate hematopoietic
      progenitor cell (HPC) expansion. However, the effects on the functional
      capacities of cultured progenitors have not been evaluated. HPC were assessed by
      flow cytometry, colony and cobblestone assays and long-term cultures (LTC) after
      culturing in the supernatant of EC stimulated by IL-1beta, IL-3 or IL-6. RESULTS:
      EC incubation with IL-6 did not improve cell expansion in comparison to non
      stimulated EC supernatant, while the HPCs' phenotype and functional capacities
      were retained. In contrast, IL-1beta and IL-3 stimulation resulted in a 10- and
      100-fold increase in cell numbers with more than 90% of these cells being
      CD33(+). Plating efficiencies and LTC initiating cells were greatest in IL-6
      supernatants, whereas the highest numbers of burst-forming units were observed
      using IL-3. IL-1beta supernatants diminished the number of 5-week cobblestone
      areas, whereas the number of 2-week cobblestone areas remained equal to freshly
      isolated HPC. Fewer 2-week cobblestones and greater amounts of 5-week
      cobblestones were observed with IL-6 and IL-3. Expanded progenitors from all
      interleukin conditions were further matured into functional granulocytes.
      CONCLUSION: IL-1beta and IL-3 stimulated endothelium induces proliferation and
      differentiation of myeloid precursors, while IL-6 treatment induced a benefit of
      HPC survival.

PMID- 18826655
TI  - Efficacious, effective, and embedded interventions: implementation research in
      infectious disease control.
AB  - BACKGROUND: Research in infectious disease control is heavily skewed towards high
      end technology; development of new drugs, vaccines and clinical interventions.
      Oft ignored, is the evidence to inform the best strategies that ensure the
      embedding of interventions into health systems and amongst populations. In this
      paper we undertake an analysis of the challenge in the development of research
      for the sustainable implementation of disease control interventions. RESULTS: We
      highlight the fundamental differences between the research paradigms associated
      with the development of technologies and interventions for disease control on the
      one hand and the research paradigms required for enhancing the sustainable uptake
      of those very same interventions within the communities on the other. We provide
      a definition for implementation research in an attempt to underscore its critical
      role and explore the multidisciplinary science needed to address the challenges
      in disease control. CONCLUSION: The greatest value for money in health research
      lies in the sustainable and effective implementation of already proven,
      efficacious solutions. The development of implementation research that can help
      provide some solutions on how this can be achieved is sorely needed.

PMID- 18826656
TI  - Genome-wide identification, organization and phylogenetic analysis of Dicer-like,
      Argonaute and RNA-dependent RNA Polymerase gene families and their expression
      analysis during reproductive development and stress in rice.
AB  - BACKGROUND: Important developmental processes in both plants and animals are
      partly regulated by genes whose expression is modulated at the post
      transcriptional level by processes such as RNA interference (RNAi). Dicers,
      Argonautes and RNA-dependent RNA polymerases (RDR) form the core components that
      facilitate gene silencing and have been implicated in the initiation and
      maintenance of the trigger RNA molecules, central to process of RNAi.
      Investigations in eukaryotes have revealed that these proteins are encoded by
      variable number of genes with plants showing relatively higher number in each
      gene family. To date, no systematic expression profiling of these genes in any of
      the organisms has been reported. RESULTS: In this study, we provide a complete
      analysis of rice Dicer-like, Argonaute and RDR gene families including gene
      structure, genomic localization and phylogenetic relatedness among gene family
      members. We also present microarray-based expression profiling of these genes
      during 14 stages of reproductive and 5 stages of vegetative development and in
      response to cold, salt and dehydration stress. We have identified 8 Dicer-like
      (OsDCLs), 19 Argonaute (OsAGOs) and 5 RNA-dependent RNA polymerase (OsRDRs) genes
      in rice. Based on phylogeny, each of these genes families have been categorized
      into four subgroups. Although most of the genes express both in vegetative and
      reproductive organs, 2 OsDCLs, 14 OsAGOs and 3 OsRDRs were found to express
      specifically/preferentially during stages of reproductive development. Of these,
      2 OsAGOs exhibited preferential up-regulation in seeds. One of the Argonautes
      (OsAGO2) also showed specific up-regulation in response to cold, salt and
      dehydration stress. CONCLUSION: This investigation has identified 23 rice genes
      belonging to DCL, Argonaute and RDR gene families that could potentially be
      involved in reproductive development-specific gene regulatory mechanisms. These
      data provide an insight into probable domains of activity of these genes and a
      basis for further, more detailed investigations aimed at understanding the
      contribution of individual components of RNA silencing machinery during
      reproductive phase of plant development.

PMID- 18826657
TI  - Septins localize to microtubules during nutritional limitation in Saccharomyces
      cerevisiae.
AB  - BACKGROUND: In Saccharomyces cerevisiae, nutrient limitation stimulates diploid
      cells to undergo DNA replication and meiosis, followed by the formation of four
      haploid spores. Septins are a family of proteins that assemble a ring structure
      at the mother-daughter neck during vegetative growth, where they control
      cytokinesis. In sporulating cells, the septin ring disassembles and septins
      relocalize to the prospore membrane. RESULTS: Here, we demonstrate that nutrient
      limitation triggers a change in the localization of at least two vegetative
      septins (Cdc10 and Cdc11) from the bud neck to the microtubules. The association
      of Cdc10 and Cdc11 with microtubules persists into meiosis, and they are found
      associated with the meiotic spindle until the end of meiosis II. In addition, the
      meiosis-specific septin Spr28 displays similar behavior, suggesting that this is
      a common feature of septins. Septin association to microtubules is a consequence
      of the nutrient limitation signal, since it is also observed when haploid cells
      are incubated in sporulation medium and when haploid or diploid cells are grown
      in medium containing non-fermentable carbon sources. Moreover, during meiosis II,
      when the nascent prospore membrane is formed, septins moved from the microtubules
      to this membrane. Proper organization of the septins on the membrane requires the
      sporulation-specific septins Spr3 and Spr28. CONCLUSION: Nutrient limitation in
      S. cerevisiae triggers the sporulation process, but it also induces the
      disassembly of the septin bud neck ring and relocalization of the septin subunits
      to the nucleus. Septins remain associated with microtubules during the meiotic
      divisions and later, during spore morphogenesis, they are detected associated to
      the nascent prospore membranes surrounding each nuclear lobe. Septin association
      to microtubules also occurs during growth in non-fermentable carbon sources.

PMID- 18826658
TI  - Ethnomedicinal plant use by Lepcha tribe of Dzongu valley, bordering
      Khangchendzonga Biosphere Reserve, in North Sikkim, India.
AB  - Lepcha is the oldest and the first tribe reported from Sikkim, India; majority of
      its population inhabiting in Dzongu valley, an officially demarcated reserve for
      Lepcha community, bordering Khangchendzonga Biosphere Reserve, in north district.
      Lepchas of Dzongu are known for their retention of rich cultural heritage. In
      view of the on-going cultural and economic changes brought in by the process of
      globalization, the immediate need was felt to document in details the under
      explored ethnomedicinal practices of Lepchas of Dzongu valley. This paper reports
      118 species, belonging to 71 families and 108 genera, under ethnomedicinal
      utility by the Lepchas for curing approximately 66 ailments, which could be
      grouped under 14 broad categories. Zingiberaceae appeared as the most used family
      (8 species and 5 genera). As per use pattern, maximum of 30.50% species are to
      cure stomach related disorders/ailments, followed by 19.49% for curing cut,
      wounds, inflammation, sprains and joint pains. Administration of medicine orally
      is recorded in 75% cases. Root and rhizome harvesting targeted 30 species. The
      changing scenario over time both at socio-cultural front and passing traditional
      knowledge interests from older to younger generation and rich ethnomicinal wealth
      of the oldest tribe of Sikkim are discussed in the light of conservation
      strategies and techniques to adopt.

PMID- 18826659
TI  - Dietary micronutrients are associated with higher cognitive function gains among
      primary school children in rural Kenya.
AB  - With the exception of iodine and Fe, there is still very limited information on
      the effect of micronutrients on cognitive function, especially among school-age
      children. The present analysis evaluates the relationship between dietary Fe, Zn
      and B vitamins (B12, B6, folate and riboflavin) and gains in cognitive test
      scores among school children in rural Kenya. Data for the present study were
      obtained from The Child Nutrition Kenya Project, a 2-year longitudinal,
      randomised controlled feeding intervention study using animal source foods.
      Dietary nutrient values were based on monthly and bimonthly 24 h recall data
      collected during the study period. In longitudinal regression analyses, available
      Fe, available Zn, vitamin B12 and riboflavin showed significant relationships
      with improved cognitive test scores, after controlling for confounders such as
      energy intake, school, socio-economic status and morbidity. Available Fe intake
      was associated with significantly higher gains in Raven's Coloured Progressive
      Matrices test scores over time. Available Zn intake was associated with
      significantly higher gains in digit span-total test scores over time, while
      vitamin B12 and riboflavin intakes were each associated with significantly higher
      gains in digit span-forward test scores over time. This analysis demonstrates the
      influence of improved dietary micronutrient status on school children's cognitive
      function.

PMID- 18826660
TI  - Ultrasound-guided core needle biopsy of parotid gland swellings.
AB  - OBJECTIVE: To determine whether ultrasound-guided core needle biopsy is a safe
      and reliable investigation in cases of parotid swelling in which fine needle
      aspiration cytology has failed to give a definitive diagnosis. DESIGN: Analysis
      of 66 ultrasound-guided core biopsy specimens of the parotid gland (the largest
      series reported thus far) sample number refers to histological samples throughout
      the paper. SUBJECTS: All the 184 cases of parotid surgery with a histological
      diagnosis were included. MAIN OUTCOME MEASURES: The sensitivity, positive
      predictive value and diagnostic accuracy of fine needle aspiration cytology and
      ultrasound-guided core needle biopsy, as compared with the final histological
      analysis. RESULTS: Of a total of 184 patients, 89.1 per cent (164/184) had benign
      parotid lesions excised. The sensitivity, positive predictive value and
      diagnostic accuracy of fine needle aspiration cytology for benign lesions were
      76.2, 84.2 and 87.5 per cent, respectively, and those of ultrasound-guided core
      needle biopsy were 91.7, 98.2 and 96.4 per cent, respectively. Twenty of 184
      patients (10.9 per cent) had malignant lesions. The sensitivity, positive
      predictive value and diagnostic accuracy of fine needle aspiration cytology for
      detection of malignant lesions were 60, 75 and 75 per cent, respectively, while
      those of ultrasound-guided core biopsy were 89, 100 and 100 per cent,
      respectively. Non-diagnostic rates were 25.8 per cent for fine needle aspiration
      cytology and 4.5 per cent for ultrasound-guided core biopsy. Only one case of
      complications (a sub-clinical haematoma) occurred in the ultrasound-guided core
      biopsy group. CONCLUSION: We propose ultrasound-guided core needle biopsy as a
      very safe and effective tool in cases of parotid swelling in which fine needle
      aspiration cytology has failed to give a definitive diagnosis.

PMID- 18826661
TI  - A simple assessment of physical activity is associated with obesity and motor
      fitness in pre-school children.
AB  - OBJECTIVE: Physical activity is an important determinant of energy balance.
      However, its impact on overweight/obesity has proved difficult to measure in pre
      school children and few studies have found significant associations. A set of
      simple questions was used to distinguish pre-school children with high and low
      physical activity, and the association of this classification with childhood
      overweight/obesity and performance in an established motor test was investigated.
      DESIGN: Survey, cross-sectional. SETTING AND SUBJECTS: Weight and height were
      measured in 12,556 children taking part in the obligatory school entrance health
      examination 2004-5 and 2005-6 in three urban and three rural Bavarian regions.
      Their parents were asked to answer a questionnaire with a set of questions on
      physical activity. RESULTS: The mean age of the children evaluated was 5.78 (sd
      0.43) years, 6535 (52.1 %) were boys. Physically active children were less likely
      to be overweight (OR = 0.786, 95 % CI 0.687, 0.898) or obese (OR = 0.655, 95 % CI
      0.506, 0.849) and achieved 6.7 (95 % CI 5.8, 7.7) % more jumps per 30 s than less
      active children in a motor test, adjusted for a number of potentially confounding
      variables. CONCLUSIONS: Classification of pre-school children as physically
      active or not, based on a small set of questions, revealed significant
      associations with overweight/obesity and a motor test. Once further validated,
      this classification might provide a valuable tool to assess the impact of
      physical activity on the risk of childhood overweight and obesity.

PMID- 18826662
TI  - What maternal factors influence the diet of 2-year-old children living in
      deprived areas? A cross-sectional survey.
AB  - OBJECTIVE: To investigate the maternal factors associated with poor diet among
      disadvantaged children. DESIGN: Survey of 300 mothers of 2-year-old children from
      areas of high deprivation in Scotland (response rate 81 %). A diet quality score
      was derived from reported consumption of carbohydrates, protein, fruit and
      vegetables, dairy products and restriction of sugary fatty foods. RESULTS: Most
      children (85 %) were classified as having a poor quality diet (low diet quality
      score). Mothers' general knowledge about healthy eating was high, but did not
      predict the quality of the children's diet. Lower frequencies of food preparation
      and serving, such as cooking with raw ingredients, providing breakfast daily and
      the family eating together, were also associated with a poorer diet. Regression
      modelling identified five significant factors. An increased risk of a poor diet
      was associated with mothers being unlikely to restrict sweets (OR = 21.63, 95 %
      CI 2.70, 173.30) or finding it difficult to provide 2-3 portions of fruit daily
      (OR = 2.94, 95 % CI 1.09, 7.95). Concern that the child did not eat enough
      increased the risk of a poor diet (OR = 2.37, 95 % CI 1.09, 5.16). Believing a
      healthy diet would help the child eat more reduced the risk of having a poor diet
      (OR = 0.28, 95 % CI 0.11, 0.74), as did providing breakfast daily (OR = 0.22, 95
      % CI 0.05, 0.99). CONCLUSIONS: Interventions to improve children's diet could
      promote more positive intentions about preparing and serving of foods,
      particularly of specific meals at which the family eats together. The benefits of
      these behaviours to the child (improved diet, weight control) should be
      emphasised.

PMID- 18826663
TI  - RAPD and mitochondrial DNA analysis of the soybean stalk weevil, Sternechus
      subsignatus (Coleoptera: Curculionidae).
AB  - Sternechus subsignatus Boheman (Curculionidae: Sternechini) is one of the primary
      Curculionidae species that reduces soybean yield in Brazil. Initially, outbreaks
      were reported in southern Brazil in 1973; but, more recent, outbreaks were
      reported in Bahia (summer 1997-1998) and Maranhao (summer 2003-2004), two states
      in northeastern Brazil. A putative related species, S. pinguis (Fabricius), was
      first detected in Salta Province, Argentina. The objective of this study was to
      evaluate intraspecific molecular polymorphisms of geographically distinct
      Sternechus populations. Randomly amplified polymorphic DNA (RAPD) profiles and
      partial mitochondrial cytochrome B (CytB) gene sequences were used to determine
      whether individual soybean stalk weevils were one of two different species and to
      infer pest invasion pattern. Putative S. pinguis and S. subsignatus populations
      were collected in San Agustin (Cruz Alta, Tucuman Province, Argentina) and
      different sampling sites in the Brazilian states of Parana, Bahia and Maranhao.
      Polymorphic bands were obtained by RAPD and analyzed by Dice coefficients.
      Populations from southern Brazil were more closely related genetically to an
      Argentinean group than the populations sampled in northeastern Brazil. The
      Londrina Co., Brazil population displayed the highest intra-population genetic
      similarity. Most of the soybean stalk weevils collected from San Agustin,
      Tucuman, Argentina were divergent from those collected in Brazil. Sequencing and
      parsimony analysis of CytB did not differentiate specimens collected in Argentina
      and Brazil. Thus, our data show that soybean stalk weevil outbreaks and
      population increases in northeastern Brazil involved local genotypes.

PMID- 18826664
TI  - Effect of coffee alkaloids and phenolics on egg-laying by the coffee leaf miner
      Leucoptera coffeella.
AB  - The recognized importance of coffee alkaloids and phenolics mediating insect
      plant interactions led to the present investigation aiming to test the hypothesis
      that the phenolics chlorogenic and caffeic acids and the alkaloid caffeine and
      some of its derivatives present in coffee leaves affect egg-laying by the coffee
      leaf miner Leucoptera (=Perileucoptera) coffeella (Guerin-Meneville & Perrottet)
      (Lepidoptera: Lyonetiidae), one of the main coffee pests in the Neotropical
      region. These phytochemicals were, therefore, quantified in leaves from 12 coffee
      genotypes and their effect on the egg-laying preference by the coffee leaf miner
      was assessed. Canonical variate analysis and partial canonical correlation
      provided evidence that increased leaf levels of caffeine favour egg-laying by the
      coffee leaf miner. An egg-laying preference bioassay was, therefore, carried out
      to specifically test this hypothesis using increasing caffeine concentrations
      sprayed on leaves of one of the coffee genotypes with the lowest level of this
      compound (i.e. Hybrid UFV 557-04 generated from a cross between Coffea racemosa
      Lour. and C. arabica L.). The results obtained allowed the recognition of a
      significant concentration-response relationship, providing support for the
      hypothesis that caffeine stimulates egg-laying by the coffee leaf miner in coffee
      leaves.

PMID- 18826665
TI  - Variability and genetic basis for migratory behaviour in a spring population of
      the aphid, Aphis gossypii Glover in the Yangtze River Valley of China.
AB  - The population dynamics, development of gonads, takeoff and flight behaviour of
      Aphis gossypii Glover were investigated in order to test whether there was
      variation of migratory ability in the spring population. Field surveys showed
      that not all the aphids overwintering on hibiscus migrated to the secondary host
      plants, and the host-alternating and host-specific life-cycle forms coexisted in
      Nanjing, China. Substantial variation in flight capacity of winged individuals,
      development of gonads and takeoff behaviour were found within the spring
      population. The frequency distribution of flight duration and the number of
      ovarioles per individual alatae exhibited two peaks, representing the migratory
      and sedentary genotypes, respectively. Significant response to directional
      selection on takeoff behaviour demonstrated the additive genetic component of
      this variation. Selection for 'takeoff' individuals caused a significant increase
      in takeoff angle from 39.8 degrees in the first selection to 68.7 degrees in the
      fifth; and, hence, screened out the migratory genotype (M), while selection for
      the sedentary individuals increased the rate of non-takeoffs significantly, and
      screened out the sedentary genotype (S). The reciprocal cross, M(female) x
      S(male), produced hybrid offspring performing significantly steeper takeoff
      angles compared with those from the cross S(female) x M(male), suggesting the
      presence of a maternal effect. On the other hand, takeoff rate was ranked as
      M(female) x S(male)=S(female) x M(male)>M>S, involving no sex-linkage and
      maternal effect. The coexistence of host-alternating and host-specific life-cycle
      forms of A. gossypii on the primary host has, as deduced from the present
      studies, a genetic basis.

PMID- 18826666
TI  - Molecular phylogeny of Pemphiginae (Hemiptera: Aphididae) inferred from nuclear
      gene EF-1alpha sequences.
AB  - Three traditional tribes of Fordini, Pemphigini and Eriosomatini comprise
      Pemphiginae, and there are two subtribes in Fordini and Pemphigini, respectively.
      Most of the species in this subfamily live heteroecious holocyclic lives with
      distinct primary host specificity. The three tribes of Pemphigini (except
      Prociphilina), Eriosomatini and Fordini use three families of plants, Salicaceae
      (Populus), Ulmaceae (Ulums) and Anacardiaceae (Pistacia and Rhus), as primary
      hosts, respectively, and form galls on them. Therefore, the Pemphigids are well
      known as gall makers, and their galls can be divided into true galls and pseudo
      galls in type. We performed the first molecular phylogenetic study of Pemphiginae
      based on molecular data (EF-1alpha sequences). Results show that Pemphiginae is
      probably not a monophylum, but the monophyly of Fordini is supported robustly.
      The monophyly of Pemphigini is not supported, and two subtribes in it, Pemphigina
      and Prociphilina, are suggested to be raised to tribal level, equal with Fordini
      and Eriosomatini. The molecular phylogenetic analysis does not show definite
      relationships among the four tribes of Pemphiginae, as in the previous
      phylogenetic study based on morphology. It seems that the four tribes radiated at
      nearly the same time and then evolved independently. Based on this, we can
      speculate that galls originated independently four times in the four tribes, and
      there is no evidence to support that true galls are preceded by pseudo-galls, as
      in the case of thrips and willow sawflies.

PMID- 18826667
TI  - Exon-primed intron-crossing (EPIC) PCR markers of Helicoverpa armigera
      (Lepidoptera: Noctuidae).
AB  - Applying microsatellite DNA markers in population genetic studies of the pest
      moth Helicoverpa armigera is subject to numerous technical problems, such as the
      high frequency of null alleles, occurrence of size homoplasy, presence of
      multiple copies of flanking sequence in the genome and the lack of PCR
      amplification robustness between populations. To overcome these difficulties, we
      developed exon-primed intron-crossing (EPIC) nuclear DNA markers for H. armigera
      based on ribosomal protein (Rp) and the Dopa Decarboxylase (DDC) genes and
      sequenced alleles showing length polymorphisms. Allele length polymorphisms were
      usually from random indels (insertions or deletions) within introns, although
      variation of short dinucleotide DNA repeat units was also detected. Mapping
      crosses demonstrated Mendelian inheritance patterns for these EPIC markers and
      the absence of both null alleles and allele 'dropouts'. Three examples of allele
      size homoplasies due to indels were detected in EPIC markers RpL3, RpS6 and DDC,
      while sequencing of multiple individuals across 11 randomly selected alleles did
      not detect indel size homoplasies. The robustness of the EPIC-PCR markers was
      demonstrated by PCR amplification in the related species, H. zea, H. assulta and
      H. punctigera.

PMID- 18826668
TI  - Two mitochondrial lineages occur in the Asian corn borer, Ostrinia furnacalis
      (Lepidoptera: Crambidae), in Japan.
AB  - The genealogy and diversity of the mitochondrial cytochrome oxidase subunit II
      (COII) gene were investigated for Ostrinia furnacalis in Japan. A preliminary
      examination of mitochondrial lineages in China and the Philippines was also made.
      Two lineages (A and B) were found in the COII gene. Lineage A was frequent
      throughout the Japanese main islands (Hokkaido, Honshu, Shikoku and Kyushu),
      while the frequency of lineage B varied among these islands. No clear patterns of
      geographical population structure were found. Population genetic features
      suggested that the O. furnacalis population harboring the lineage A mitochondria
      expanded in the recent past, while lineage B showed weak signals of a population
      expansion. It is not clear whether the two lineages of mtDNA evolved in separate
      or identical geographical regions. We discuss two hypotheses regarding the two
      lineages of mtDNA: a cryptic race/species hypothesis and a selective sweep
      hypothesis.

PMID- 18826669
TI  - Language as shaped by the brain.
AB  - It is widely assumed that human learning and the structure of human languages are
      intimately related. This relationship is frequently suggested to derive from a
      language-specific biological endowment, which encodes universal, but
      communicatively arbitrary, principles of language structure (a Universal Grammar
      or UG). How might such a UG have evolved? We argue that UG could not have arisen
      either by biological adaptation or non-adaptationist genetic processes, resulting
      in a logical problem of language evolution. Specifically, as the processes of
      language change are much more rapid than processes of genetic change, language
      constitutes a "moving target" both over time and across different human
      populations, and, hence, cannot provide a stable environment to which language
      genes could have adapted. We conclude that a biologically determined UG is not
      evolutionarily viable. Instead, the original motivation for UG--the mesh between
      learners and languages--arises because language has been shaped to fit the human
      brain, rather than vice versa. Following Darwin, we view language itself as a
      complex and interdependent "organism," which evolves under selectional pressures
      from human learning and processing mechanisms. That is, languages themselves are
      shaped by severe selectional pressure from each generation of language users and
      learners. This suggests that apparently arbitrary aspects of linguistic structure
      may result from general learning and processing biases deriving from the
      structure of thought processes, perceptuo-motor factors, cognitive limitations,
      and pragmatics.

PMID- 18826699
TI  - Emotional responses to music: the need to consider underlying mechanisms.
AB  - Research indicates that people value music primarily because of the emotions it
      evokes. Yet, the notion of musical emotions remains controversial, and
      researchers have so far been unable to offer a satisfactory account of such
      emotions. We argue that the study of musical emotions has suffered from a neglect
      of underlying mechanisms. Specifically, researchers have studied musical emotions
      without regard to how they were evoked, or have assumed that the emotions must be
      based on the "default" mechanism for emotion induction, a cognitive appraisal.
      Here, we present a novel theoretical framework featuring six additional
      mechanisms through which music listening may induce emotions: (1) brain stem
      reflexes, (2) evaluative conditioning, (3) emotional contagion, (4) visual
      imagery, (5) episodic memory, and (6) musical expectancy. We propose that these
      mechanisms differ regarding such characteristics as their information focus,
      ontogenetic development, key brain regions, cultural impact, induction speed,
      degree of volitional influence, modularity, and dependence on musical structure.
      By synthesizing theory and findings from different domains, we are able to
      provide the first set of hypotheses that can help researchers to distinguish
      among the mechanisms. We show that failure to control for the underlying
      mechanism may lead to inconsistent or non-interpretable findings. Thus, we argue
      that the new framework may guide future research and help to resolve previous
      disagreements in the field. We conclude that music evokes emotions through
      mechanisms that are not unique to music, and that the study of musical emotions
      could benefit the emotion field as a whole by providing novel paradigms for
      emotion induction.

PMID- 18826726
TI  - Vitamins and cardiovascular disease.
AB  - CVD is a major cause of mortality and morbidity in the Western world. In recent
      years its importance has expanded internationally and it is believed that by 2020
      it will be the biggest cause of mortality in the world, emphasising the
      importance to prevent or minimise this increase. A beneficial role for vitamins
      in CVD has long been explored but the data are still inconsistent. While being
      supported by observational studies, randomised controlled trials have not yet
      supported a role for vitamins in primary or secondary prevention of CVD and have
      in some cases even indicated increased mortality in those with pre-existing late
      stage atherosclerosis. The superiority of combination therapy over single
      supplementation has been suggested but this has not been confirmed in trials.
      Studies have indicated that beta-carotene mediates pro-oxidant effects and it has
      been suggested that its negative effects may diminish the beneficial effects
      mediated by the other vitamins in the supplementation cocktail. The trials that
      used a combination of vitamins that include beta-carotene have been
      disappointing. However, vitamin E and vitamin C have in combination shown long
      term anti-atherogenic effects but their combined effect on clinical endpoints has
      been inconsistent. Studies also suggest that vitamins would be beneficial to
      individuals who are antioxidant-deficient or exposed to increased levels of
      oxidative stress, for example, smokers, diabetics and elderly patients,
      emphasising the importance of subgroup targeting. Through defining the right
      population group and the optimal vitamin combination we could potentially find a
      future role for vitamins in CVD.

PMID- 18826727
TI  - Genetic potential for the regulation of variability in body lipid and protein
      content of European whitefish (Coregonus lavaretus).
AB  - Animals may have target levels for lipid and protein stores which they try to
      maintain by feedback mechanisms. Thus, variation in initial body composition may
      be related to subsequent feed utilisation, for animals to maintain body
      composition in homeostasis. We assessed whether such relationships are
      genetically determined within a farmed population of European whitefish
      (Coregonus lavaretus) grown either on fishmeal or soyabean-meal diets. Soyabean
      meal is an increasingly-used ingredient in aquaculture feeds. Fish from thirty
      five paternal families were analysed for initial body lipid and protein content,
      and for subsequent daily weight gain, daily feed intake, feed efficiency and
      their lipid and protein components. The results showed that none of the
      correlations of initial body lipid percentage with subsequent growth and feed
      utilisation were statistically significant. In contrast, low initial protein
      percentage was related to increased subsequent weight gain, protein gain and
      protein retention efficiency. This led to reversed ranking of families during
      growth for body protein percentage. Thus, mechanisms maintaining stable body
      lipid percentage across the population were weak, whereas the mechanisms
      stabilising body protein percentage were strong and successful. This explains the
      observations that cascades of lipid deposition occur during fish growth, leading
      to high amounts of phenotypic and genetic variation for percentage body lipid. In
      contrast, protein percentage remains phenotypically and genetically more
      invariable, reducing the potential for selective breeding. The soyabean-meal
      diet, in turn, induced only weak genotype x diet interactions, aiding in the
      genetic improvement of farmed fish to adapt to future feeds.

PMID- 18826728
TI  - ALaRMED: adverse events in low-risk chest pain patients receiving continuous ECG
      monitoring in the emergency department: a survey of Canadian emergency
      physicians.
AB  - OBJECTIVE: Current guidelines suggest that most patients who present to an
      emergency department (ED) with chest pain should be placed on a continuous
      electrocardiographic monitoring (CEM) device. We surveyed emergency physicians to
      determine their perception of current occupancy rates of CEM and to assess their
      attitudes toward prescribing monitors for low-risk chest pain patients in the ED.
      METHODS: We conducted a cross-sectional, self-administered Internet and mail
      survey of a random sample of 300 members of the Canadian Association of Emergency
      Physicians. Main outcome measures included the perceived frequency of fully
      occupied monitors in the ED and physicians' willingness to forgo CEM in certain
      chest pain patients. RESULTS: The response rate was 66% (199 respondents). The
      largest group of respondents (43%; 95% confidence interval [CI] 36%-50%)
      indicated that monitors were fully occupied 90%-100% of the time during their
      most recent ED shift. When asked how often they were forced to choose a patient
      for monitor removal because of the limited number of monitors, 52% (95% CI 45%
      60%) of respondents selected 1-3 times per shift. Ninety percent (95% CI 84%-93%)
      of respondents indicated that they would forgo CEM in certain cardiac chest pain
      patients if there was good evidence that the risk of a monitor-detected adverse
      event was very low. CONCLUSION: Emergency physicians report that monitors are
      often fully occupied in Canadian EDs, and most are willing to forgo CEM in
      certain chest pain patients. A large prospective study of CEM in low-risk chest
      pain patients is warranted.

PMID- 18826729
TI  - Errors, near misses and adverse events in the emergency department: what can
      patients tell us?
AB  - OBJECTIVE: We sought to determine whether patients or their families could
      identify adverse events in the emergency department (ED), to characterize patient
      reports of errors and to compare patient reports to events recorded by health
      care providers. METHODS: This was a prospective cohort study in a quaternary care
      inner city teaching hospital with approximately 40,000 annual visits. ED patients
      were recruited for participation in a standardized interview within 24 hours of
      ED discharge and a follow-up interview 3-7 days after discharge. Responses
      regarding events were tabulated and compared with physician and nurse notations
      in the medical record and hospital event reporting system. RESULTS: Of 292
      eligible patients, 201 (69%) were interviewed within 24 hours of ED discharge,
      and 143 (71% of interviewees) underwent a follow-up interview 3-7 days after
      discharge. Interviewees did not differ from the base ED population in terms of
      age, sex or language. Analysis of patient interviews identified 10 adverse events
      (5% incident rate; 95% confidence interval [CI] 2.41%-8.96%), 8 near misses (4%
      incident rate; 95% CI 1.73%-7.69%) and no medical errors. Of the 10 adverse
      events, 6 (60%) were characterized as preventable (2 raters; kappa=0.78, standard
      error [SE] 0.20; 95% CI 0.39-1.00; p=0.01). Adverse events were primarily related
      to delayed or inadequate analgesia. Only 4 out of 8 (50%) near misses were
      intercepted by hospital personnel. The secondary interview elicited 2 out of 10
      adverse events and 3 out of 8 near misses that had not been identified in the
      primary interview. No designation (0 out of 10) of an adverse event was recorded
      in the ED medical record or in the confidential hospital event reporting system.
      CONCLUSION: ED patients can identify adverse events affecting their care.
      Moreover, many of these events are not recorded in the medical record. Engaging
      patients and their family members in identification of errors may enhance patient
      safety.

PMID- 18826730
TI  - A door-to-needle time of 30 minutes or less for myocardial infarction
      thrombolysis is possible in rural emergency departments.
AB  - OBJECTIVE: The Canadian Emergency Cardiac Care Coalition, the American Heart
      Association and similar groups have established a benchmark for the
      administration of thrombolytics in acute myocardial infarction (AMI) care as a
      door-to-needle (DTN) time of 30 minutes or less. Previous research suggests that
      this goal is not being achieved in Canada. The purpose of this study was to
      determine whether the target DTN time of 30 minutes or less for thrombolysis
      could be met in 2 rural Ontario emergency departments (EDs). METHODS: We
      conducted a retrospective chart review and obtained descriptive data for each
      case, including demographic information and the Canadian Emergency Department
      Triage and Acuity Scale (CTAS) score. Visit timeline data were also collected and
      included the time during which patients saw a physician, had an electrocardiogram
      (ECG), received thrombolytic therapy and were discharged from the ED. Relevant
      time intervals, such as the median DTN time, were calculated. RESULTS: A total of
      454 charts were reviewed for patients with a diagnosis of AMI who were seen
      between 1996 and 2007. The final sample consisted of 101 patients who received
      thrombolytics (63% men) whose median age was 67 years and median CTAS score was
      Level II (Emergent). The median door-to-ECG time was 6 minutes, door-to-physician
      time was 8 minutes and DTN time was 27 minutes; 58% of patients received
      thrombolytics within 30 minutes. CONCLUSION: A DTN time of 30 minutes or less is
      achievable in rural EDs.

PMID- 18826731
TI  - An interventional study to improve the quality of analgesia in the emergency
      department.
AB  - OBJECTIVE: We sought to document the adequacy of acute pain management in a high
      volume urban emergency department and the impact of a structured intervention.
      METHODS: We conducted a prospective, single-blind, pre- and postintervention
      study on patients who suffered minor-to-moderate trauma. The intervention
      consisted of structured training sessions on emergency department (ED) analgesia
      practice and the implementation of a voluntary analgesic protocol. RESULTS:
      Preintervention data showed that only 340 of 1000 patients (34%) received
      analgesia. Postintervention data showed that 693 of 700 patients (99%) received
      analgesia, an absolute increase of 65% (95% CI 61%-68%), and that delay to
      analgesia administration fell from 69 (standard deviation [SD] 54) minutes to 35
      (SD 43) minutes. Analgesics led to similar reductions in visual analog pain scale
      ratings during the pre- and postintervention phases (4.5 cm, SD 2.0 cm, and 4.3
      cm, SD 3.0 cm, respectively). CONCLUSION: Our multifaceted ED pain management
      intervention was highly effective in improving quality of analgesia, timeliness
      of care and patient satisfaction. This protocol or similar ones have the
      potential to substantially improve pain management in diverse ED settings.

PMID- 18826732
TI  - A brief note about likelihood ratios.

PMID- 18826733
TI  - Canadian Association of Emergency Physicians Sepsis Guidelines: the optimal
      management of severe sepsis in Canadian emergency departments.
AB  - INTRODUCTION: Optimal management of severe sepsis in the ED has evolved rapidly.
      The purpose of these guidelines is to review key management principles for
      Canadian emergency physicians, utilizing an evidence-based grading system.
      METHODS: Key areas in the management of septic patents were determined by members
      of the CAEP Critical Care Interest Group (C4). Members of C4 were assigned a
      question to be answered after literature review, based on the Oxford grading
      system. After completion, each section underwent a secondary review by another
      member of C4. A tertiary review was conducted by additional external experts, and
      modifications were determined by consensus. Grading was based on peer-reviewed
      publications only, and where evidence was insufficient to address an important
      topic, a "practice point" was provided based on group opinion. RESULTS: The
      project was initiated in 2005 and completed in December 2007. Key areas which
      were reviewed include the definition of sepsis, the use of invasive procedures,
      fluid resuscitation, vasopressor/inotrope use, the importance of culture
      acquisitionin the ED, antimicrobial therapy and source control. Other areas
      reviewed included the use of corticosteroids, activated protein C, transfusions
      and mechanical ventilation. CONCLUSION: Early sepsis management in the ED is
      paramount for optimal patient outcomes. The CAEP Critical Care Interest Group
      Sepsis Position Statement provides a framework to improve the ED care of this
      patient population.

PMID- 18826734
TI  - CAEP standards: ivory tower emergency medicine?

PMID- 18826736
TI  - Simulation training for emergency medicine residents: time to move forward.

PMID- 18826738
TI  - Terminating resuscitation for out-of-hospital cardiac arrest?

PMID- 18826739
TI  - A motor vehicle collision and dark corners. Diagnosis: Horner syndrome due to
      carotid artery dissection.

PMID- 18826740
TI  - Pediatric myth: fever and petechiae.
AB  - A child presenting with petechiae and fever is assumed to have meningococcemia or
      another form of bacterial sepsis and therefore to require antibiotics, blood
      cultures, cerebrospinal fluid analysis and hospital admission. A review of the
      literature challenges this statement and suggests that a child presenting with
      purpura (or petechiae), an ill appearance and delayed capillary refill time or
      hypotension should be admitted and treated for meningococcal disease without
      delay. Conversely, a child with a petechial rash, which is confined to the
      distribution of the superior vena cava, is unlikely to have meningococcal
      disease. Outpatient therapy in this context is appropriate. In other children, a
      reasonable approach would be to draw blood for culture and C-reactive protein
      (CRP) while administering antibiotics. If the CRP is normal, these children could
      be discharged to follow-up in 1 day, whereas children with CRP values greater
      than 6 mg/L would be admitted.

PMID- 18826742
TI  - Left vertebral artery dissection causing bilateral internuclear ophthalmoplegia.
AB  - A 21-year-old woman presented to the emergency department 1 day after a fall. On
      the day of presentation, she awoke with horizontal diplopia and posterior neck
      pain. Based on clinical findings, she was diagnosed with bilateral internuclear
      ophthalmoplegia. A conventional angiogram identified a left vertebral artery
      dissection. She was started on anticoagulant therapy, with gradual improvement of
      her diplopia over several months. Diplopia is frequently seen in the emergency
      department. Internuclear ophthalmoplegia is a cause of binocular diplopia and is
      important to recognize because it indicates a brainstem lesion requiring
      neurologic evaluation.

PMID- 18826743
TI  - Central diabetes insipidus misdiagnosed as acute gastroenteritis in a pediatric
      patient.
AB  - This case report describes an unusual presentation of nausea, vomiting and
      diarrhea, which was misdiagnosed as acute gastroenteritis in a 6-year-old girl.
      The patient later returned to the emergency department (ED) with severe
      dehydration from idiopathic central diabetes insipidus (DI). At her first visit,
      this previously healthy patient presented with mild dehydration, signs of acute
      gastroenteritis and normal urine output. Her brother had experienced similar
      symptoms a few days earlier. She tolerated an oral fluid challenge and was
      discharged from the ED with stable vital signs. Two days later, the patient
      returned with severe dehydration, resolving diarrhea and persistent vomiting. She
      was admitted to the pediatric intensive care unit. Magnetic resonance imaging
      illustrated an absent posterior pituitary enhancing signal, which demonstrated a
      loss of function in that region. There were no other abnormalities. The patient
      subsequently received desmopressin with improving clinical status and was
      discharged on the eighth hospital day. DI is a rare disease, but can be fatal if
      left undiagnosed. It should, therefore, be considered in the differential
      diagnosis of a dehydrated patient with an unexpectedly low urine specific
      gravity.

PMID- 18826746
TI  - Real-world physician and patient behaviour across countries: Disease-Specific
      Programmes - a means to understand.
AB  - BACKGROUND/OBJECTIVES: Treatment guidelines and strategies are often based on
      data from randomized controlled trials and observational clinical studies. These
      sources drive treatment decisions, yet the data they provide may have limited
      relevance to the wider population in real-world clinical practice due to the
      narrow selection criteria applied to patients in trials. Information used to
      inform clinical practice and improve patient outcomes can, therefore, be
      unreflective of real-world clinical situations. The purpose of this article is to
      assess the value of Adelphi Disease Specific Programmes (DSPs) as sources of real
      world data. METHODS: DSPs are large, multinational, observational studies of
      clinical practice for a range of common chronic diseases. Treatment practice data
      are collected by physicians (n = 700) who are asked to provide information for
      the next 10 patients consulting for a specific condition. These patients (n =
      7000) are also invited to fill out a self-completion form providing their own
      assessment of symptoms, expectations and quality of life. ANALYSES: This article
      provides examples of the statistical techniques that have been employed to
      analyse the data in terms of cost/burden of illness, quality of life, disease
      severity and progression, compliance and adherence to therapy, impact of
      treatment guidelines and analyses of unmet need. CONCLUSIONS: DSPs can support
      clinical understanding of how diseases are managed including rationale for doctor
      decision-making and patient attitudes to their condition. Comparisons with other
      data sources and limitations of the programmes are discussed (including the fact
      that, unlike claims databases and registries, the DSPs are cross-sectional and
      not longitudinal).

PMID- 18826747
TI  - Self-reported healthcare decision-makers' attitudes towards economic evaluations
      of medical technologies.
AB  - BACKGROUND: Increasing costs have generated concern among governments and
      healthcare providers who have realized the need for cost containment measures and
      more efficient resource utilization. Health economics is one potential source of
      information that can make healthcare more efficient. SCOPE: This review article
      summarizes the published literature on self-reported attitudes of healthcare
      decision-makers towards economic evaluations of medical technologies and examines
      the extent to which economic evaluations are used in health policy decisions.
      METHODS: A systematic literature review of published English language studies was
      conducted using MEDLINE, EMBASE, and HEED from January 1995 to December 2007.
      FINDINGS: Fifty-five articles investigated the use of economic evaluations on
      three levels of decision-making: central, local, and physician level. Results
      indicate the use of economic evaluation information increased from limited/minor
      to moderate use. The influence of economic evaluations increased with the level
      of centralization of healthcare system. Barriers to use health economics research
      varied across levels and included health economics research-related barriers such
      as timely availability, lack of credibility, insufficient methodological quality
      and decision-context-related barriers including limited decision makers'
      knowledge, inflexibility in healthcare budgets and variability among healthcare
      organizations. CONCLUSIONS: For consistent policy-making it is important that
      similar recommendations for cost-effective interventions and programs are
      developed at all levels and that implementation is promoted by incorporating the
      appropriate incentives in healthcare provision.

PMID- 18826748
TI  - Impact of secondary hyperparathyroidism on disease progression, healthcare
      resource utilization and costs in pre-dialysis CKD patients.
AB  - BACKGROUND AND OBJECTIVES: Secondary hyperparathyroidism (SHPT) can lead to
      significant morbidity, mortality, and additional healthcare resource utilization
      in chronic kidney disease (CKD) stage 5. The objective of this study was to
      examine healthcare costs and utilization, and the risks of dialysis or mortality,
      among pre-dialysis CKD patients with and without SHPT. RESEARCH DESIGN AND
      METHODS: This retrospective cohort study examined insurance claims from 66 644
      adult, pre-dialysis, CKD patients with and without SHPT during a 72-month period.
      Annualized estimates of healthcare costs and utilization, and disease progression
      to dialysis or death following index CKD diagnosis were compared. RESULTS: Post
      index annualized costs and inpatient healthcare resource utilization was higher
      in those with SHPT in both unadjusted and adjusted (controlling for gender, age,
      plan type, payer type, geographic region, physician specialty, pre-index co
      morbidities, and pre-index total healthcare costs), and unmatched and matched
      analyses. Kaplan-Meier analysis demonstrated that the rate of progression to
      dialysis or death was higher for CKD with SHPT compared to CKD without SHPT, and
      Cox proportional hazard models suggested that CKD patients with SHPT were more
      than four to five times as likely to initiate dialysis or die as compared to CKD
      without SHPT. CONCLUSION: SHPT in pre-dialysis CKD patients is associated with
      significantly greater healthcare costs, inpatient hospitalizations, and a faster
      rate of disease progression compared to pre-dialysis CKD without SHPT. Since
      observational studies are designed to demonstrate associations rather than
      causality, further investigation is required to confirm these findings.

PMID- 18826749
TI  - Comparison of morning versus evening dosing and 24-h post-dose efficacy of
      travoprost compared with latanoprost in patients with open-angle glaucoma .
AB  - OBJECTIVE: To compare the IOP-lowering efficacy of a.m.-dosed travoprost and
      latanoprost at 24-h post-dose. RESEARCH DESIGN AND METHODS: Open-angle glaucoma
      patients not naive to prostaglandin therapy and currently controlled on p.m.
      dosed (2100) latanoprost (n = 21) or travoprost (n = 30) had baseline IOPs
      measured at 0900. In a randomized, single-masked, crossover design, patients
      received travoprost (Travatan ? ) or latanoprost (Xalatan ? ) at 0900 for 4
      weeks, then were crossed over to receive the second prostaglandin for another 4
      weeks. Treatment IOP was measured at 0900 prior to morning dose at both 4 and 8
      week visits. Patient dosing preference (a.m./p.m.) was surveyed on exit. MAIN
      OUTCOME MEASURE: Intraocular pressure (IOP). ? Travatan is a registered trade
      name of Alcon Laboratories, Inc., Fort Worth, TX, USA ? Xalatan is a registered
      trade name of Pfizer, New York, NY, USA. RESULTS: The mean IOP in the first
      period when all patients were dosed in the evening was assessed 12 h after dosing
      at 09:00 and it was similar in the two treatment groups (mean +/- standard
      deviation: 17.9 +/- 2.7 mmHg for travoprost versus 17.7 +/- 2.5 mmHg for
      latanoprost, p = 0.812). In the a.m.-dosing crossover comparison, the 24-h post
      dose IOP was significantly lower ( p < 0.001) on travoprost (16.9 +/- 3.1 mmHg)
      compared to latanoprost (18.6 +/- 3.3 mmHg). In the exit survey, 51% of patients
      preferred a.m.-dosing. CONCLUSIONS: a.m.-dosed travoprost is superior to a.m.
      dosed latanoprost by 1.7 mmHg at 24-h post-dose.

PMID- 18826750
TI  - Pioglitazone versus rosiglitazone treatment in patients with type 2 diabetes and
      dyslipidemia: cost-effectiveness in the US.
AB  - OBJECTIVES: Pioglitazone hydrochloride (Actos ? ) and rosiglitazone maleate
      (Avandia ? ) are members of the thiazolidinedione (TZD) class of oral anti
      diabetic drugs (OADs) and are used to treat type 2 diabetes mellitus (T2DM).
      Greater beneficial effects on lipids have been demonstrated with pioglitazone,
      however. Study objectives were to evaluate the long-term cost-effectiveness of
      pioglitazone compared to rosiglitazone in treating patients with T2DM and
      dyslipidemia, and determine the extent to which reported beneficial lipid effects
      of pioglitazone would improve clinical and economic outcomes through reduced
      macrovascular complications. ? Actos is a trade name of Takeda Pharmaceuticals
      Co. Ltd., Deerfield, IL, US ? Avandia is a trade name of GlaxoSmithKline,
      Research Triangle, NC, US. RESEARCH DESIGN AND METHODS: The validated CORE
      Diabetes Model (CDM) was used to simulate changes in glycosylated hemoglobin
      (HbA(1c)), complications, and direct medical costs. Baseline parameters came from
      a multi-center, double-blind trial comparing lipid and glycemic effects of
      pioglitazone (n = 400) and rosiglitazone (n = 402) among individuals with T2DM
      and untreated dyslipidemia. Sensitivity analyses examined the impact of cohort,
      clinical, and cost inputs on incremental cost effectiveness ratios (ICERs).
      RESULTS: In the base case, pioglitazone was associated with mean (standard
      deviation [SD]) quality-adjusted life years (QALYs) of 7.476 (0.123) vs. 7.326
      (0.128) for rosiglitazone. Pioglitazone had $3038 higher total direct costs, but
      $580 lower complication costs. Risks of four cardiovascular complications were
      reduced with pioglitazone (relative risks 0.860-0.942), while risks of 17 other
      complications were slightly higher (relative risks 1.001-1.056). The ICER for
      pioglitazone treatment was $20 171/QALY. Results were most sensitive to the
      effects of HbA(1c), high-density lipoprotein-cholesterol, overall lipid effects,
      and pioglitazone acquisition costs. CONCLUSIONS: Study limitations include issues
      of generalizability of the trial patient population, as well as inability to
      capture non-adherence and variation in 'real-world' treatment patterns.
      Nevertheless, pioglitazone (when compared to rosiglitazone) was found to have
      long-term value as a treatment option for T2DM patients with dyslipidemia treated
      within the US payer setting.

PMID- 18826751
TI  - The rate of decline of joint space width in patients with osteoarthritis of the
      knee: a systematic review and meta-analysis of randomized placebo-controlled
      trials of chondroitin sulfate .
AB  - BACKGROUND: Chondroitin sulfate has been shown to relieve pain and improve
      functional limitation in patients with osteoarthritis (OA) of the knee in
      numerous clinical trials and meta-analyses. Its role as a potential structure
      modifying drug for knee OA, however, remains controversial. OBJECTIVE: To perform
      a meta-analysis of randomized double-blind placebo-controlled clinical trials to
      assess the efficacy of chondroitin sulfate as a structure-modifying drug for knee
      OA. RESEARCH DESIGN AND METHODS: A Medline search was conducted from 1996 through
      2007 and five articles that reported results from three trials were identified;
      one additional trial was identified through review of presentations at annual
      rheumatology meetings. There was no evidence of heterogeneity across the trials
      and results were pooled using a fixed effects meta-analysis. RESULTS: Pooled
      results demonstrated a small significant effect of chondroitin sulfate on the
      reduction in rate of decline in minimum joint space width of 0.07 mm/year (95% CI
      0.03, 0.10) that corresponded to an effect size of 0.26 (95% CI 0.14, 0.38) (p <
      0.0001). This result was robust in sensitivity analyses. LIMITATIONS: The
      individual studies included in the meta-analysis varied in the number of patients
      enrolled and the techniques used to acquire knee radiographs and to measure joint
      space width. CONCLUSION: These results demonstrate that chondroitin sulfate is
      effective for reducing the rate of decline in minimum joint space width in
      patients with OA of the knee. Chondroitin sulfate may have a role as a structure
      modifying agent in the management of patients with knee OA.

PMID- 18826752
TI  - Statin discontinuation: an underestimated risk?
AB  - Statin treatment is essential for the prevention of vascular disease. Despite the
      established benefits of statins, discontinuation of these agents is frequent.
      Whether statin discontinuation leads to adverse outcomes is still debated and the
      most convincing evidence is mainly restricted to patients who experienced an
      acute vascular event. It is important to establish if this phenomenon extends to
      other populations, like those without vascular disease but with a high calculated
      risk. Overall, it appears that even a brief discontinuation of statins might be
      harmful. Therefore, statin treatment should not be interrupted except if there is
      a very good reason. Moreover, patients should be instructed as to why they must
      adhere to their medication. Adherence should be monitored regularly.

PMID- 18826753
TI  - Time course changes of the striatum neuropil after unilateral dopamine depletion
      and the usefulness of the contralateral striatum as a control structure.
AB  - INTRODUCTION: After unilateral dopamine depletion, some ipsilateral alterations
      occur and the contralateral structure has been utilized as control. OBJECTIVE:
      Our aim is to analyse the evolution of the ultrastructural alterations of the
      ipsilateral and contralateral striata of the 6-hydroxydopamine lesioned rats to
      demonstrate that the contralateral striatum should not be used as control
      structure. METHODS: After the surgery and the rotation behavior evaluation,
      animals were killed from 3 to 120 days after lesioning, and their striata were
      compared with those of aged rats. RESULTS: The ultrastructural analysis shows
      increased diameter of the synaptic ending in ipsilateral (since the third day)
      and contralateral striata (since day 30) and an increase in perforated synaptic
      contacts. CONCLUSION: Our data suggest that the contralateral striatum should not
      be taken as control structure at least after 20-30 days after lesioning, as the
      alterations found here may result in wrong interpretations when comparing with
      the ipsilateral-lesioned one.

PMID- 18826754
TI  - Neurological deficits associated with the elastase-induced aneurysm model in
      rabbits.
AB  - OBJECTIVE: Although the rabbit elastase-induced aneurysm model is currently used
      widely for endovascular research and device testing, procedural causes leading to
      animal morbidity and mortality have not yet been clearly described. We conducted
      a retrospective study to analyse factors contributing to neurological deficits in
      rabbits that underwent the elastase-induced aneurysm creation procedure at our
      research center from 2002 to 2005 in order to improve the technique and reduce
      procedure-related morbidity and mortality. METHODS: A total sample of 38 animals
      that underwent the procedure under the same conditions was analysed in two
      groups: animals that presented neurological deficits (ND, n=15) and animals that
      were neurological deficit free (NDF, n=23). Data were collected by reviewing the
      animal records and radiographic images from the procedures. Statistical analyses
      using the Mann-Whitney test, unpaired t-test with Welch correction and Fisher's
      exact tests were performed to compare the two groups based on variables
      associated with endothelial injury and activation of the coagulation cascade.
      RESULTS: The variables of animal weight (signifying state of health of the
      animal), total procedure time, total balloon occlusion time and clot formation
      were found to be significantly and/or very significantly correlated to ND
      presentation. DISCUSSION: Successful creation of the rabbit elastase-induced
      aneurysm model depends on careful control over several technical details.
      Important variables governing outcome have been identified here. A specific,
      improved endovascular arrangement that facilitates maneuvering of the devices and
      reduces the risk of air emboli is presented.

PMID- 18826755
TI  - Late onset autosomal dominant Charcot-Marie-Tooth 2 neuropathy in a Costa Rican
      family.
AB  - OBJECTIVE: To describe the clinical, electrophysiologic and morphologic features
      of a Costa Rican family with an autosomal dominant inherited Charcot-Marie-Tooth
      (CMT) neuropathy. METHODS: The field study took place in Costa Rica, Central
      America. Seven patients underwent neurological examinations and standard
      electrodiagnostic tests, and a sural nerve biopsy was taken from one patient.
      Fifteen family members were screened for gene defects associated with CMT
      disease. RESULTS: Characteristic features of this family were a late age of onset
      (35-56 years), positive sensory symptoms and muscle cramps. Based on
      electrodiagnostic and morphologic data, the patients were classified as having a
      CMT2 neuropathy. The CMT1A duplication/HNPP deletion and point mutations in genes
      PMP22, MPZ, Cx32 and EGR2 implicated in the most common types of CMT disease were
      excluded. Subsequently, almost all known CMT loci were excluded by linkage
      analysis. DISCUSSION: Features of this family were a late age of onset and
      positive sensory symptoms. This new autosomal dominant CMT neuropathy is
      associated with an unknown gene defect.

PMID- 18826756
TI  - Injection of muscimol, a GABAa agonist into the anterior thalamic nucleus,
      suppresses hippocampal neurogenesis in amygdala-kindled rats.
AB  - The relationship between neurogenesis and epilepsy remains to be solved so far,
      although aberrant electric circuit recognized in epilepsy might be involved in
      neurogenesis. In this study, neurogenesis and the proliferation of astrocytes in
      the subgranular zone of the hippocampus were explored using unilateral amygdala
      kindled rats with or without muscimol, a gamma-aminobutyric acid a (GABAa)
      agonist injection into the bilateral anterior thalamic nuclei (AN). Muscimol
      injection significantly ameliorated the behavioral scores of epilepsy without any
      significant alteration on the electroencephalography recorded at the stimulated
      basolateral amygdala, thus suggesting that muscimol injection might affect the
      secondary generalization, but not the initial discharge itself. The number of
      bromodeoxyuridine (BrdU), BrdU/doublecortin and BrdU/glial fibrillary acidic
      protein-positive cells in the subgranular zone of kindled animals increased
      markedly. Muscimol injection significantly suppressed neurogenesis, but not the
      proliferation of astrocyte, in the subgranular zone of the non-stimulated side,
      probably through the suppression of secondary generalization via AN. The results
      might indicate the underlying relationships between neurogenesis and epilepsy,
      that epileptic propagation in unilateral amygdala-kindled rats might go through
      AN into the contralateral side with subsequent neurogenesis, although further
      studies need to clarify the hypothesis.

PMID- 18826757
TI  - Real-time multi-site multi-parametric monitoring of rat brain subjected to
      traumatic brain injury.
AB  - INTRODUCTION: Traumatic brain injury (TBI) is one of the major causes of death in
      the world, with at least ten million serious traumatic brain injuries occurring
      annually; nevertheless, the pathophysiologic events taking place immediately
      after the injury are not yet fully known. OBJECTIVE: To study the effects of TBI
      on brain hemodynamic, metabolic and ionic homeostasis using the multi-parametric
      monitoring system. This system enables real-time monitoring of cerebral blood
      flow (CBF), mitochondrial NADH redox state, extracellular levels of K+, H+, DC
      potential, ECoG and ICP. METHODS: In order to find the best brain location for
      the monitoring device in relation to the fluid percussion injury site, we used
      the multi-site multi-parametric monitoring system. Two groups of rats were
      connected to four monitoring probes at four different locations near the injury
      site, two in each hemisphere. We monitored CBF, NADH redox state, tissue
      reflectance and DC steady potential in each of the four sites. RESULTS: Under
      anoxia, the initial CBF decrease was followed by an increase, NADH level
      increased, the reflectance decreased and dc potential showed a biphasic response,
      in all 4 locations. However, following fluid percussion injury, there was a
      significant variability in the responses in each of the 4 monitored locations.
      CONCLUSION: The advantage of the multi-parametric-monitoring approach for
      enhanced understanding of the injured brain was indicated. Moreover, we showed
      that contralateral monitoring of the injured brain gives good indication for the
      events taking place following fluid percussion brain injury.

PMID- 18826764
TI  - Democracy in action: the House of Commons Health Committee's inquiry into Dental
      Services in England.

PMID- 18826765
TI  - An audit of dentine hypersensitivity treatments in six general dental practices
      in Scotland.
AB  - AIMS: This investigation sought to: (a) determine the agents used by nine
      dentists to treat dentine hypersensitivity and measure their effectiveness; (b)
      evaluate the adoptive ease and apparent success of the most effective treatment
      when used by all nine dentists; and (c) validate a novel categorical ranking
      score for dentine hypersensitivity. METHODS: A clinical audit methodology was
      used in the setting of general dental practice. In the initial data-collection
      round, patients presenting with dentine hypersensitivity were treated using the
      dentist's favoured regimen. Evaluation of agent effectiveness was made by patient
      completion of a pre- and post-treatment visual analogue scale (VAS) for the
      frequency (f) and severity (s) of hypersensitivity. A four-point categorical
      ranking scale (CRS) was also used to assess the impact of hypersensitivity upon
      lifestyle (L) (1=No sensitivity/effect on what I eat/drink; 2=Sometimes
      sensitive, rarely interfering with what I eat/drink; 3=Sometimes sensitive,
      occasionally interfering with what I eat/drink; 4=Always sensitive, always
      interfering with what I eat/drink). The most successful treatment was determined
      and used by all participating dentists. Its effectiveness was then assessed using
      the same criteria. RESULTS: Four agents were routinely used to treat
      hypersensitivity: (Duraphat (D) (Colgate), Duraphat & Sensodyne (DS)
      (GlaxoSmithKline), Sensodyne (S) (GlaxoSmithKline), Seal & Protect (SP) (De Trey,
      Dentsply). All produced statistically significant (P<0.001) reductions in VAS
      (Tukey) and CRS (Kruskal-Wallis) scores, except for DS and S. Of these, the
      greatest percentage reduction was seen for SP (f=72.01%, s=71.19%, L=45.98%).
      When SP was applied by all dentists, similar percentage reductions were seen
      (f=68.74%, s=75.85%, L=38.33%). The CRS, in both data-collection rounds,
      correlated well with the corresponding VAS scores (Spearman R for f=0.77
      (P<0.001) and for s=0.80 (P<0.001). CONCLUSION: For the dentists in this audit,
      the use of SP was found to be reliable and predictable. The CRS provided a simple
      and reliable measure of dentine hypersensitivity. Subject to validation in a
      larger study, this could be used in a future audit as an alternative to multiple
      VAS scores.

PMID- 18826766
TI  - Central giant cell granuloma in palate associated with orthodontic treatment.
AB  - A case report of a central giant cell granuloma in the palate, which arose after
      orthodontic treatment, is presented with a review of relevant literature.
      Treatment options and clinical implications are also discussed.

PMID- 18826767
TI  - The need for leadership and vision in dentistry: a personal view.

PMID- 18826768
TI  - The need for leadership and vision in dentistry: a personal view.

PMID- 18826769
TI  - Mentoring. A quality assurance tool for dentists. Part 1: the need for mentoring
      in dental practice.
AB  - This paper introduces the concept of mentoring and its use in dental practice. It
      explains how there has been a drive for quality in all areas of healthcare in the
      United Kingdom (UK), and that clinical audit and clinical governance are two of
      the quality assurance tools that have been developed. It suggests that the most
      important factor in the provision of quality care is the dentist and that it is
      therefore essential that dentists are given support and encouragement by their
      peers, together with recognition of good performance. The next section of the
      paper considers factors that hinder a dentist's quality of performance. It
      explains that there are multiple stresses in dental practice and, if they are not
      managed and controlled, that they can lead to professional burnout, anxiety and
      depression. One of the most important stressors that can impact on the quality of
      patient care is the constraint of time, which can frequently result from pressure
      from third parties such as managers and administrators. Dentists often feel
      isolated. The final section of the paper describes how dentists may be supported.
      Techniques include developing special interests within oral healthcare, career
      development, good human resource management, peer review and study groups, and
      coaching and mentoring. The nature of these last two techniques is discussed and
      the authors conclude that the best tool for supporting the quality of performance
      of dentists is mentoring.

PMID- 18826770
TI  - Effect of distance from curing light tip to restoration surface on depth of cure
      of composite resin.
AB  - AIMS: While light-activating composite resins, the light tip may not always be
      close to the surface of the restoration. This may be intentional in an attempt to
      create a ramp cure. The aim of this study was to determine the effect of a range
      of separation distances between the light tip and the restoration surface on the
      depth of composite cure for different types of light-curing units with a broad
      range of outputs. METHODS: Three halogen light units, one plasma arc-curing (PAC)
      light unit and two light-emitting diode (LED) curing lights in clinical use were
      tested, and a total of 570 restorations cured in a two-part human tooth model at
      separations ranging from 0 to 15 mm. The tooth was disassembled and depth of cure
      determined using the scrape test ISO 4049. Light intensity was also measured at
      each separation distance for each light. RESULTS: The depth of cure was generally
      found to decrease as the separation distance increased for all lights at the
      various cure times. However, the effect of increasing the separation distance was
      less than anticipated. The depth of cure was also related to the light output.
      CONCLUSIONS: Depth of composite cure was directly related to intensity and
      duration of light exposure and inversely related to distance of the light source
      from the surface for halogen and plasma lights. However, the effect of increasing
      the separation distance up to 15 mm was less than expected. Altering the
      separation distance in order to modify the polymerisation characteristics is
      unlikely to be effective.

PMID- 18826771
TI  - An audit of concomitant dental anomalies with maxillary talon cusps in a group of
      children from Hong Kong.
AB  - AIM: To investigate the prevalence of various concomitant dental anomalies in
      Hong Kong children with true talon cusps on the permanent maxillary incisors.
      METHODS: Dental records and radiographs of a group of Hong Kong Chinese primary
      schoolchildren with true talon cusps (half crown height or more) on one or more
      permanent maxillary incisors were selected and studied retrospectively. The
      prevalence of various dental anomalies in this group of children was compared
      with that of the general population of Hong Kong Chinese children of similar age.
      RESULTS: A total of 11,537 records were reviewed and 58 children with true talon
      cusps on one or more permanent maxillary incisors were identified. A total of 69
      permanent maxillary incisors were affected, of which all except one were lateral
      incisors. Dens evaginatus on premolars, supernumerary teeth in the anterior
      maxilla, and hypodontia were found in 5 (8.6%), 5 (8.6%), and 5 (8.6%) cases
      respectively. The prevalence of supernumerary teeth was significantly higher in
      children with true talon cusps as compared with the results of two previous
      general studies of Chinese children of similar age (P<0.05, Fisher's exact test).
      CONCLUSION: Children with true talon cusps on the permanent maxillary incisors
      were more frequently affected by supernumerary teeth in the anterior maxilla.
      Further studies with a larger sample are needed to confirm a true association.

PMID- 18826772
TI  - Factors influencing the career aspirations and preferred modes of working in
      recent dental graduates in Wales.
AB  - INTRODUCTION: In England and Wales, National Health Service (NHS) primary dental
      care services are now commissioned on a local basis. In planning for the future,
      it is important that commissioning authorities have a clear understanding of the
      perspectives of recent dental graduates: vocational dental practitioners (VDPs).
      OBJECTIVES: This study investigated the career aspirations and preferred modes of
      working of VDPs in Wales. METHODOLOGY: Data were collected via a postal
      questionnaire, comprising 37 closed and open questions, mailed to all 59 VDPs in
      Wales. RESULTS: A total of 53 (90%) VDPs participated, of whom 47 saw their
      future in general dental practice: 5, 35, and 7 indicating a preference to work
      in the NHS, mixed (NHS and private), and private sector, respectively. None
      selected the Community Dental Service as their preferred vocation. More than half
      of all respondents intended to undertake a postgraduate qualification within the
      next five years and 22 wished to specialise. Of the 53 VDPs, 44 were concerned
      that lack of NHS contracts would limit where they could practise, and agreed that
      family and other social commitments were a significant influence on choice of
      practice location. Access to high-quality premises and continuing professional
      development were agreed as important by 41 VDPs. A majority (37) agreed that
      private dentistry was an attractive alternative to NHS dentistry. Of the
      respondents, 38 (22 females, 16 males) expected to work part-time at some point
      in the future and 14 said they would consider a career outside dentistry. Only
      nine VDPs agreed that they would be happy working in a single-handed practice and
      even fewer (six) indicated they would be happy working for a corporate body.
      CONCLUSIONS: Numerous factors impact on the career aspirations of VDPs. These
      factors have been quantified in this study, and healthcare-commissioning bodies
      need to be aware of them when planning future dental care provision in Wales.

PMID- 18826774
TI  - Do general practices provide equitable access to physical activity interventions?
AB  - BACKGROUND: Exercise referral schemes are widespread across England. National
      guidance emphasises the need to engage groups that are disadvantaged. AIM: To
      examine the influence of socioeconomic deprivation on referral to, and use of,
      exercise referral schemes. DESIGN OF STUDY: Cross-sectional analysis of patients
      referred by general practices to exercise referral schemes between 2004 and 2006.
      SETTING: Six primary care trusts (PCTs) in Greater London. METHOD: Routine data
      about patients who had been referred to exercise referral schemes were used to
      estimate risk ratios for referral by general practice deprivation quintile, odds
      ratios (ORs) for uptake, and ORs for completion of exercise referral schemes by
      patients' deprivation status quintile. RESULTS: All 317 general practices in the
      six PCTs were included in the referral analysis. Referrals were less likely from
      general practices serving advantaged socioeconomic areas (adjusted risk ratio for
      trend across deprivation quintiles 0.84; 95% confidence interval [CI] = 0.76 to
      0.93). This study found no association between patients' deprivation status and
      their likelihood of taking up (adjusted OR, least versus most deprived quintile
      1.05; 95% CI = 0.83 to 1.33) or completing the scheme (adjusted OR 1.23; 95% CI =
      0.84 to 1.79). CONCLUSION: General practices within areas of deprivation were
      more likely to refer patients to exercise referral schemes than practices in more
      advantaged areas. Once referred, it was found that patients living in areas of
      deprivation were as likely to take up and to complete the scheme as those living
      in more advantaged locations. Research is needed to identify the organisational
      and contextual factors that allow this pattern of service delivery, which appears
      to facilitate access to care among patients who live in areas of deprivation.

PMID- 18826775
TI  - October focus.

PMID- 18826776
TI  - Is personal care important in the diagnosis of depression in older people?

PMID- 18826777
TI  - Cardiac rehabilitation: it works so why isn't it done?

PMID- 18826778
TI  - Primary care management of major depression in patients aged > or =55 years:
      outcome of a randomised clinical trial.
AB  - BACKGROUND: Late-life depression is associated with chronic illness, disability,
      and a poor prognosis. Primary care management may be in need of improvement. AIM:
      To compare the effects of an intervention programme that aims to improve the
      identification, diagnosis, and treatment of depression in patients aged > or =55
      years with the effects of usual care. DESIGN OF STUDY: Cluster randomised
      controlled trial. SETTING: General practices in the Netherlands. METHOD: Trained
      GPs performed the intervention and their practice assistants conducted the
      screenings. Patients were screened with the 15-item Geriatric Depression Scale
      (GDS-15) and given a consultation with the GP who diagnosed depression with the
      mood module of the Primary Care Evaluation of Mental Disorders (PRIME-MD).
      Antidepressant treatment was proposed. Primary outcomes were measured with the
      Montgomery Asberg Depression Rating Scale (MADRS). Trained independent research
      assistants performed independent evaluations in both arms. RESULTS: Eighteen
      practices (23 GPs) were allocated to the intervention and 16 practices (20 GPs)
      to usual care. From June 2000 to September 2002, 3937 patients were screened; 579
      patients had a positive score on the GDS-15, 178 had major depression, of whom
      145 participated in the trial. MADRS scores for the intervention group dropped
      from 21.66 at baseline to 9.23 at 6 months, and the usual care group from 20.94
      at baseline to 11.45 at 6 months. MADRS scores decreased during the year in both
      arms. For the intervention group, these scores increased between 6 and 12 months.
      CONCLUSION: The programme resulted in lower MADRS scores in the intervention
      group than in the usual care group, but only at the end of the intervention, at 6
      months after baseline.

PMID- 18826780
TI  - Screening older people with musculoskeletal pain for depressive symptoms in
      primary care.
AB  - BACKGROUND: Older patients presenting to GPs with musculoskeletal pain are at
      high risk of having concurrent depression. AIM: To investigate the performance of
      ultra-short (1-4 items tools) screening questions used during the consultation,
      and through a patient questionnaire to detect depressive symptoms among older
      adults presenting with musculoskeletal pain to general practice. DESIGN OF STUDY:
      Cross-sectional survey, linked GP consultation data. SETTING: General practices
      in central Cheshire, UK. METHOD: Consecutive patients aged > or =50 years
      presenting with non-inflammatory musculoskeletal pain were eligible to
      participate. GPs screened all patients in the consultation for the presence of
      depressive symptoms using two questions. All patients were sent a postal
      questionnaire within 1 week of consultation containing the Hospital Anxiety and
      Depression Scale and the written version of the depression screening questions.
      RESULTS: The total number of patients included in the study was 428. In total,
      35.5% of consulters had comorbid depressive symptoms, with 13.5% experiencing
      moderate or severe symptoms. Just over half of participants (n = 218/242; 51.4%)
      screened positive on self-administered screening at home compared with only 78
      (20.8%) on GP-administered screening in the consultation. There was little
      difference between GP-administered and self-administered screening in the
      probability of depressive symptoms among those who screened positive with regard
      to exhibiting signs of having depressive symptoms. CONCLUSION: Older patients
      consulting their GP with musculoskeletal pain frequently have comorbid mental ill
      health. Ultrashort depression screening questions administered during the
      consultation miss a large number of those with depressive symptoms, including six
      out of eight patients with severe symptoms. An improvement in the performance of
      screening questions in this patient group or narrowing the definition of 'high
      risk' from all patients aged > or =50 years presenting with musculoskeletal pain
      could help to improve detection.

PMID- 18826781
TI  - Help-seeking preferences for psychological distress in primary care: effect of
      current mental state.
AB  - BACKGROUND: There is much debate over when it is appropriate to intervene
      medically for psychological distress, and limited evidence on patients'
      perspectives about a broad range of possible treatment options. It is currently
      unclear whether preferences may differ for those patients with milder symptoms
      compared to those experiencing more severe distress. AIM: To determine patient
      preferences for professional, informal, and alternative help for psychological
      distress in primary care, and the impact of their current mental state on these.
      DESIGN OF STUDY: Cross-sectional survey in seven general practices across
      suburban/urban London. METHOD: Participants were 1357 consecutive general
      practice attenders aged 18 years and over. The main outcome measure was the
      General Health Questionnaire 12-item version and a questionnaire on help-seeking
      preferences. RESULTS: Overall, only 47% of participants reported wanting 'some
      help' if feeling stressed, worried, or low and it was affecting their daily life.
      Those currently experiencing mild-to-moderate distress preferred informal sources
      of help such as friends/family support, relaxation/yoga, exercise/sport, or
      massage along with general advice from their GP and talking therapies. Self-help
      (books/leaflets or computer/internet) was not popular at any level of distress,
      and less favoured by those with mild-to-moderate distress (odds ratio [OR] =
      0.50; 95% confidence interval [CI] = 0.35 to 0.70). Those experiencing severe
      distress were much more likely to want talking therapies (OR = 3.43, 95% CI =
      2.85 to 4.14), tablets (OR = 3.07, 95% CI = 2.00 to 4.71), and support groups (OR
      = 3.07, 95% CI = 1.72 to 5.47). CONCLUSION: People with mild-to-moderate distress
      appear to prefer informal sources of help and those involving human contact,
      compared to medication or self-help. This has implications for the implementation
      of potential interventions for psychological distress in primary care.

PMID- 18826782
TI  - Improving the uptake of pulmonary rehabilitation in patients with COPD:
      qualitative study of experiences and attitudes.
AB  - BACKGROUND: Pulmonary rehabilitation can improve the quality of life and ability
      to function of patients with chronic obstructive pulmonary disease (COPD). It may
      also reduce hospital admission and inpatient stay with exacerbations of COPD.
      Some patients who are eligible for pulmonary rehabilitation may not accept an
      offer of it, thereby missing an opportunity to improve their health status. AIM:
      To identify a strategy for improving the uptake of pulmonary rehabilitation.
      DESIGN OF STUDY: Qualitative interviews with patients. SETTING: Patients with
      COPD were recruited from a suburban general practice in north-east Derbyshire,
      UK. METHOD: In-depth interviews were conducted on a purposive sample of 16
      patients with COPD to assess their concerns about accepting an offer of pulmonary
      rehabilitation. Interviews were analysed using grounded theory. RESULTS: Fear of
      breathlessness and exercise, and the effect of pulmonary rehabilitation on
      coexisting medical problems were the most common concerns patients had about
      taking part in the rehabilitation. The possibility of reducing the sensation of
      breathlessness and regaining the ability to do things, such as play with their
      grandchildren, were motivators to participating. CONCLUSION: A model is proposed
      where patients who feel a loss of control as their disease advances may find that
      pulmonary rehabilitation offers them the opportunity to regain control.
      Acknowledging patients' fears and framing pulmonary rehabilitation as a way of
      'regaining control' may improve patient uptake.

PMID- 18826783
TI  - Impact of the 2004 GMS contract on practice nurses: a qualitative study.
AB  - BACKGROUND: The new GMS contract has led to practice nurses playing an important
      role in the delivery of the Quality and Outcomes Framework (QOF). AIM: This study
      investigated how practice nurses perceive the changes in their work since the
      contract's inception. DESIGN OF STUDY: A qualitative approach, sampling practice
      nurses from practices in areas of high and low deprivation, with a range of QOF
      scores. SETTING: Glasgow, UK. METHOD: Individual interviews were conducted,
      audiotaped, transcribed, and analysed using a thematic approach. RESULTS: Three
      themes emerged: roles and incentives, workload, and patient care. Practice nurses
      were positive about the development of their professional role since the
      introduction of the new GMS contract but had mixed views about whether their
      status had changed. Views on incentives (largely related to financial rewards)
      also varied, but most felt under-rewarded, irrespective of practice QOF
      achievement. All reported a substantial increase in workload, related to
      incentivised QOF domains with greater 'box ticking' and data entry, and less time
      to spend with patients. Although the structure created by the new contract was
      generally welcomed, many were unconvinced that it improved patient care and felt
      other important areas of care were neglected. Concern was also expressed about a
      negative effect of the QOF on holistic care, including ethical concerns and
      detrimental effects on the patient-nurse relationship, which were regarded as a
      core value. CONCLUSIONS: The new GMS contract has given practice nurses increased
      responsibility. However, discontent about how financial gains are distributed and
      negative impacts on core values may lead to detrimental long-term effects on
      motivation and morale.

PMID- 18826784
TI  - Deprivation, demography, and the distribution of general practice: challenging
      the conventional wisdom of inverse care.
AB  - It is generally believed that the most deprived populations have the worst access
      to primary care. Lord Darzi's review of the NHS responds to this conventional
      wisdom and makes a number of proposals for improving the supply of GP services in
      deprived communities. This paper argues that these proposals are based on an
      incomplete understanding of inverse care which underestimates the degree to
      which, relative to their healthcare needs, older populations experience low
      availability of primary care. Many deprived practices appear to have a better
      match between need and supply than practices serving affluent but ageing
      populations. However, practices serving the oldest and most deprived populations
      have the worst availability of all.

PMID- 18826786
TI  - Managing hyperglycaemia.

PMID- 18826787
TI  - Children's Commissioner.

PMID- 18826788
TI  - Community hospitals.

PMID- 18826789
TI  - Undergraduate education.

PMID- 18826790
TI  - APMS contracts.

PMID- 18826791
TI  - Is there a polyclinic alternative acceptable to general practice? The 'beacon'
      practice model.

PMID- 18826792
TI  - Cracking the system.

PMID- 18826794
TI  - Recipe for success?

PMID- 18826796
TI  - A patient's diary: episode 22--please doctor, don't leave me now!

PMID- 18826797
TI  - Top Tips in 2 minutes.

PMID- 18826798
TI  - Obesity--not a child protection issue.

PMID- 18826799
TI  - An idiot's guide to medicine.

PMID- 18826800
TI  - Neurosonographical follow-up in patients with spontaneous cervical artery
      dissection.
AB  - OBJECTIVE: Neurovascular ultrasound (nUS) is widely used as a screening and
      monitoring tool in patients with spontaneous cervical artery dissection (sCAD).
      The aim of the study was to describe the sonographical course of the affected
      arteries in patients with a MRI-proven sCAD by repetitive nUS. METHODS: Thirty
      seven consecutive patients aged<60 years with 1.5 T MRI-proven sCAD were
      prospectively investigated by nUS, and within 48 hours after admission before
      MRI. The patients were re-investigated after 6 months and again after a period>12
      months. RESULTS: Forty-nine sCAD were detected in 37 patients; 24 lesions (49%)
      were located in the internal carotid arteries (ICA), and 25 (51%) in the
      vertebral arteries (VA). An arterial occlusion was found in 13 arteries (27%).
      The recanalization rate of occluded arteries was 62%. Regression of
      stenosis/occlusion within the first 6 months was found in 34 (69%) of the
      affected arteries, while between 6 and >12 months, the improvement rate was lower
      (19%). A complete recanalization without residual stenosis after 6 months was
      found in 39%. In only one artery, initial high grade ICA stenosis progressed to
      complete persistent occlusion (2%). DISCUSSION: The course of arterial stenosis
      or occlusion caused by sCAD is highly dynamic during the first 6 month after the
      event. The vast majority of arteries show regression of stenosis or
      recanalization of initial occlusion. Only a minority of patients experience a
      persistent deterioration of the vessel status.

PMID- 18826802
TI  - Vascular neurology: a winding but illuminating road of progress.

PMID- 18826803
TI  - Matrix metalloproteinases in intracerebral hemorrhage.
AB  - PURPOSE: The objective of this study is to review the role of matrix
      metalloproteinases in intracerebral hemorrhage, which is associated with
      hypertension, head trauma and premature birth. MATERIALS AND METHODS: A PubMed
      search of literature pertaining to this study was conducted in April 2008 using
      specific keyword search terms pertaining to intracerebral hemorrhage and matrix
      metalloproteinases. Some papers are not cited here as it is not possible to be
      all inclusive or due to the space limit from the journal. DISCUSSION: The
      prognosis following ICH is more detrimental than that of ischemic strokes. Matrix
      metalloproteases have been implicated in the pathogenesis of brain damage
      following ICH. The goal of this review is to bring together recent diverse data
      concerning the roles of matrix metalloproteinases after intracerebral hemorrhage,
      which includes the role of matrix metalloproteinases in central nervous system,
      matrix metalloproteinases in animal models and humans of intracerebral
      hemorrhage, the relationship between matrix metalloproteinases and
      neuroinflammation, neuronal death, blood-brain barrier disruption and interaction
      with other molecules, as well as treatment of intracerebral hemorrhage with anti
      matrix metalloproteinases agents. Besides deleterious roles in the acute period
      of intracerebral hemorrhage, some matrix metalloproteinases function in the later
      stages following intracerebral hemorrhage may have beneficial remodeling
      activity. CONCLUSION: At present, the experimental data support the use of
      pharmacologic anti-matrix metalloproteinases strategies in the acute periods
      following intracerebral hemorrhage to alleviate injury.

PMID- 18826805
TI  - Ischemic optic neuropathy.
AB  - Ischemic optic neuropathy is the most frequent cause of vision loss in middle
      age. Clinical and laboratory research studies have begun to clarify the natural
      history, clinical presentation, diagnostic criteria and pathogenesis of various
      ischemic nerve injuries. As a result, physicians are acquiring new tools to aid
      in the diagnosis and potential treatment of ischemic nerve injury. The aim of
      this review is to examine recent data on anterior and posterior ischemic optic
      neuropathy and to provide a framework for physicians to manage and counsel
      affected individuals.

PMID- 18826804
TI  - Cell adhesion molecules and ischemic stroke.
AB  - OBJECTIVE: To describe the role of adhesion molecules in ischemic stroke.
      METHODS: A PubMed search of literature pertaining to this study was conducted in
      April 2008 using specific keyword search terms pertaining to stroke and various
      listed subtopics related to adhesion molecules. RESULTS: An important
      contribution of beta2-integrins (CD11/CD18), intercellular adhesion molecule and
      P-selectin in the recruitment of leukocytes as well as platelets in the post
      ischemic cerebral microvasculature has been defined in related studies.
      Immunoblockade or genetic deletion of these adhesion molecules has been shown to
      reduce infarct volume, edema, behavioral deficits and/or mortality in different
      animal models of ischemic stroke. Anti-adhesion agents also appear to widen the
      therapeutic window for thrombolytic therapy in these experimental models. An
      emerging role of inflammatory signaling pathways has also been addressed in
      modulating adhesion properties of post-ischemic cerebral microvasculature.
      Despite the promising data obtained from animal studies, few clinical trials
      assessing anti-adhesion therapy in ischemic stroke have failed to show efficacy.
      DISCUSSION: Several experiments using cell surface adhesion molecules as targets
      of stroke therapy are promising yet inadequate. Clinical trials using immune
      blockade of adhesion molecules by antibodies have failed due to immune reactions
      of the host. Further clinical trials are needed to test the efficacy of humanized
      antibodies or non-immunogenic agents that interfere with cell adhesion
      mechanisms. Adhesion blocking strategies seem to be effective particularly at
      reperfusion and use of these strategies with thrombolytic therapies justifies a
      continued effort to define the role of adhesion molecules in the pathophysiology
      of cerebral ischemia-reperfusion.

PMID- 18826806
TI  - Migraine and stroke: current perspectives.
AB  - OBJECTIVE: The purpose of this article is to review the latest concepts regarding
      migraine and ischemic stroke. In addition, focal neurological deficits and MRI
      changes in migraine patients will be reviewed. METHODS: A PubMed search of
      neurological literature pertaining to this study was conducted using specific
      keyword search terms pertaining to migraine and ischemic stroke. RESULTS:
      Migraine, especially with aura, is a relative risk factor for stroke.
      Neuroimaging demonstrates the posterior circulation as being most vulnerable,
      although the reason for this distribution is unclear. Factors that may contribute
      to stroke in migraine include changes during cortical spreading depression with
      hyper- or hypoperfusion of neural tissue, vasospasm and endothelial dysfunction.
      Estrogen affects migraine expression as well as cerebral circulation, yet most
      women with migraine without aura are not at increased risk. Co-morbidity with
      patent foramen ovale can be mechanism of both disorders via presumed lack of
      filtration of microemboli or toxic substances; however, closure with reversal of
      right to left shunt seems to be more beneficial for cryptogenic stroke than
      migraine. Migraine and stroke are found in specific genetic disorders such as
      CADASIL, HERNS and MELAS giving clues to genetic factors. Stroke associated with
      migraine treatments such as ergots or triptans is rare, and usually associated
      with special circumstances such as overuse or concomitant thrombogenic
      conditions. CONCLUSION: Although true migrainous infarction is rare, our
      understanding of the subtle associations between migraine and cerebrovascular
      behavior is expanding.

PMID- 18826807
TI  - Pseudo-subarachnoid hemorrhage in a patient with acute cerebellar infarction.
AB  - OBJECTIVE: Hyperdensity in the basal cisterns on computed tomography (CT) brain
      scan is a diagnostic feature in subarachnoid hemorrhage. However, false
      enhancement of the subarachnoid space on CT scan may be seen in diffuse
      neurological conditions with acute presentation. This is the first reported case
      of a 'focal lesion' (acute cerebellar infarct) producing a 'pseudo-subarachnoid
      hemorrhage' secondary to increased intracranial pressure. CLINICAL PRESENTATION:
      A 42-year-old man presented with acute onset of left hemiataxia and neck pain. CT
      brain scan showed a left cerebellar infarct. During the admission, he had sudden
      onset of altered sensorium, and an emergency CT scan showed diffuse cerebral
      edema and hyperdensity of the basal cisterns. The patient then developed sudden
      cardiac arrest and all resuscitative measures failed. Autopsy showed no evidence
      of subarachnoid hemorrhage. CONCLUSION: Pseudo-subarachnoid hemorrhage is a rare
      clinical entity. It should be considered as a possibility in the evaluation and
      management of patients presenting acutely with CT brain scan showing hyperdensity
      of the basal cisterns and vascular imaging revealing absence of any aneurysm or
      vascular malformation.

PMID- 18826808
TI  - Use of perfusion- and diffusion-weighted imaging in differential diagnosis of
      acute and chronic ischemic stroke and multiple sclerosis.
AB  - OBJECTIVE: To investigate differences in lesions and surrounding normal appearing
      white matter (NAWM) by perfusion-weighted imaging (PWI) and diffusion-weighted
      imaging (DWI) in patients with acute and chronic ischemic stroke and multiple
      sclerosis (MS). METHODS: Study subjects included 45 MS patients, 22 patients with
      acute ischemic stroke and 20 patients with chronic ischemic stroke. All subjects
      underwent T2-weighted imaging (WI), flair attenuated inversion recovery (FLAIR),
      DWI and dynamic contrast enhanced PWI. Apparent diffusion coefficient (ADC) and
      mean transit time (MTT) maps were generated and values were calculated in the
      acute and chronic ischemic and demyelinating lesions, and in NAWM for distances
      of 5, 10 and 15 mm. Fifty-three acute ischemic and 33 acute demyelinating
      lesions, and 775 chronic ischemic and 998 chronic demyelinating lesions, were
      examined. Univariate, multivariate and data mining analyses were used to examine
      the feasibility of a prediction model between different lesion types. Correctly
      and incorrectly classified lesions, true positive (TP), false positive (FP) and
      precision rates were calculated. RESULTS: Patients with acute ischemic lesions
      presented more prolonged mean MTT values in lesions (p=0.002) and surrounding
      NAWM for distances of 5, 10 and 15 mm (all p<0.0001) than those with acute
      demyelinating lesions. In multinomial logistic regression analysis, 65 of 86
      acute lesions were correctly classified (75.6%). The TP rates were 81.1% for
      acute ischemic lesions and 66.7% for acute demyelinating lesions. The FP rates
      were 33.3% for acute ischemic and 18.9% for acute demyelinating lesions. The
      precision was 79.6% for classification of acute ischemic lesions and 68.8% for
      prediction of acute demyelinating lesions. The logistic model tree decision
      algorithm revealed that prolonged MTT of surrounding NAWM for a distance of 15 mm
      (> or =7459.2 ms) was the best classifier of acute ischemic versus acute
      demyelinating lesions. Patients with chronic ischemic lesions presented higher
      mean ADC (p<0.0001) and prolonged MTT (p=0.013) in lesions, and in surrounding
      NAWM for distances of 5, 10 and 15 mm (all p<0.0001), compared to the patients
      with chronic demyelinating lesions. Data mining analyses did not show reliable
      predictability for correctly discerning between chronic ischemic and chronic
      demyelinating lesions. The precision was 56.7% for classification of chronic
      ischemic and 58.9% for prediction of chronic demyelinating lesions. DISCUSSION:
      We found prolonged MTT values in lesions and surrounding NAWM of patients with
      acute and chronic ischemic stroke when compared to MS patients. The use of PWI is
      a promising tool for differential diagnosis between acute ischemic and acute
      demyelinating lesions. The results of this study contribute to a better
      understanding of the extent of hemodynamic abnormalities in lesions and
      surrounding NAWM in patients with MS.

PMID- 18826809
TI  - Application of hidden Markov random field approach for quantification of
      perfusion/diffusion mismatch in acute ischemic stroke.
AB  - The perfusion/diffusion 'mismatch model' in acute ischemic stroke provides the
      potential to more accurately understand the consequences of thrombolytic therapy
      on an individual patient basis. Few methods exist to quantify mismatch extent
      (ischemic penumbra) and none have shown a robust ability to predict infarcted
      tissue outcome. Hidden Markov random field (HMRF) approaches have been used
      successfully in many other applications. The aim of the study was to develop a
      method for rapid and reliable identification and quantification of
      perfusion/diffusion mismatch using an HMRF approach. An HMRF model was used in
      combination with automated contralateral identification to segment normal tissue
      from non-infarcted tissue with perfusion abnormality. The infarct was used as a
      seed point to initialize segmentation, along with the contralateral mirror
      tissue. The two seeds were then allowed to compete for ownership of all
      unclassified tissue. In addition, a novel method was presented for quantifying
      tissue salvageability by weighting the volume with the degree of hypoperfusion,
      allowing the penumbra voxels to contribute unequal potential damage estimates.
      Simulated and in vivo datasets were processed and compared with results from a
      conventional thresholding approach. Both simulated and in vivo experiments
      demonstrated a dramatic improvement in accuracy with the proposed technique. For
      the simulated dataset, the mean absolute error decreased from 171.9% with
      conventional thresholding to 2.9% for the delay-weighted HMRF approach. For the
      in vivo dataset, the mean absolute error decreased from 564.6% for thresholding
      to 34.2% for the delay-weighted HMRF approach. The described method represents a
      significant improvement over thresholding techniques.

PMID- 18826810
TI  - Rate of arterial occlusion in patients with acute ischemic stroke.
AB  - OBJECTIVE: Computed tomographic angiography (CTA) was invented more than 20 years
      ago, but only gained acceptance recently, thanks to advancements in the computer
      technology. It can demonstrate areas of arterial stenosis or occlusion with
      accuracy nearly that of digital subtraction angiography (DSA). It is also able to
      clearly illustrate calcification, which is more difficult to define on magnetic
      resonance angiography and is not clearly depicted on DSA. METHODS: Our
      retrospective study attempted to clarify the rate of occlusion or stenosis in the
      patients with acute ischemic stroke. RESULTS: Over the period of 7 months, 93
      consecutive patients were admitted with acute ischemic stroke. Fifty-six patients
      underwent CTA and were included in this study. Most of the patients were admitted
      after 6 hours following onset of symptoms. There were 28 men and 28 women, and
      80.4% of the cohort was of African-American origin. The majority of strokes were
      attributed to small-vessel disease (25/56). The rest of the cases were deemed
      secondary to atheroembolism (15/56), cardioembolism (9/56) or of unclear etiology
      (7/56). In 24 (42.9%) patients, CTA failed to reveal any abnormalities of the
      cerebrovascular tree. CTA demonstrated arterial occlusion in ten (17.9%) patients
      and stenosis of extracranial or intracranial arteries on the symptomatic side in
      22 (39.2%) patients. There was very good correlation between CTA and ultrasound
      techniques (carotid duplex and transcranial Doppler). CTA was superior in
      demonstrating distal intracranial stenosis. CONCLUSION: Overall, CTA is an
      extremely valuable and fast way to emergently evaluate the cerebrovascular
      anatomy, making it very useful for pre-thrombolysis evaluation of patients with
      ischemic stroke.

PMID- 18826811
TI  - Neonatal stroke.
AB  - OBJECTIVE: The purpose of this manuscript is to review various clinical and
      neuroimaging features of vascular pathology in the fetus and neonate. METHODS: A
      PubMed search of literature from 1978 to 2007 was performed using key search
      terms. Scientific papers pertinent to fetal and neonatal strokes were included
      and analysed. RESULTS: The analysis of the multiple causes of fetal and neonatal
      vascular compromise including maternal, placental, infectious,
      metabolic/prothrombotic, traumatic and cardiac factors, current therapy and
      outcome data, is presented and discussed throughout the length of the paper.
      CONCLUSION: With increasing vigilance among physicians and improved neuroimaging
      modalities, the diagnosis of neonatal stroke is now made earlier, with increasing
      frequency and greater accuracy.

PMID- 18826812
TI  - Rise and persistence of global M1T1 clone of Streptococcus pyogenes.
AB  - The resurgence of severe invasive group A streptococcal infections in the 1980s
      is a typical example of the reemergence of an infectious disease. We found that
      this resurgence is a consequence of the diversification of particular strains of
      the bacteria. Among these strains is a highly virulent subclone of serotype M1T1
      that has exhibited unusual epidemiologic features and virulence, unlike all other
      streptococcal strains. This clonal strain, commonly isolated from both
      noninvasive and invasive infection cases, is most frequently associated with
      severe invasive diseases. Because of its unusual prevalence, global spread, and
      increased virulence, we investigated the unique features that likely confer its
      unusual properties. In doing so, we found that the increased virulence of this
      clonal strain can be attributed to its diversification through phage mobilization
      and its ability to sense and adapt to different host environments; accordingly,
      the fittest members of this diverse bacterial community are selected to survive
      and invade host tissue.

PMID- 18826813
TI  - Pandemic influenza and excess intensive-care workload.
AB  - In The Netherlands a major part of preparedness planning for an epidemic or
      pandemic consists of maintaining essential public services, e.g., by the police,
      fire departments, army personnel, and healthcare workers. We provide estimates
      for peak demand for healthcare workers, factoring in healthcare worker
      absenteeism and using estimates from published epidemiologic models on the
      expected evolution of pandemic influenza in relation to the impact on peak surge
      capacity of healthcare facilities and intensive care units (ICUs). Using various
      published scenarios, we estimate their effect in increasing the availability of
      healthcare workers for duty during a pandemic. We show that even during the peak
      of the pandemic, all patients requiring hospital and ICU admission can be served,
      including those who have non-influenza-related conditions. For this rigorous task
      differentiation, clear hierarchical management, unambiguous communication, and
      discipline are essential and we recommend informing and training non-ICU
      healthcare workers for duties in the ICU.

PMID- 18826814
TI  - Risk factors for Nipah virus encephalitis in Bangladesh.
AB  - Nipah virus (NiV) is a paramyxovirus that causes severe encephalitis in humans.
      During January 2004, twelve patients with NiV encephalitis (NiVE) were identified
      in west-central Bangladesh. A case-control study was conducted to identify
      factors associated with NiV infection. NiVE patients from the outbreak were
      enrolled in a matched case-control study. Exact odds ratios (ORs) and 95%
      confidence intervals (CIs) were calculated by using a matched analysis. Climbing
      trees (83% of cases vs. 51% of controls, OR 8.2, 95% CI 1.25-infinity) and
      contact with another NiVE patient (67% of cases vs. 9% of controls, OR 21.4, 95%
      CI 2.78-966.1) were associated with infection. We did not identify an increased
      risk for NiV infection among persons who had contact with a potential
      intermediate host. Although we cannot rule out person-to-person transmission,
      case-patients were likely infected from contact with fruit bats or their
      secretions.

PMID- 18826815
TI  - Deforestation and vectorial capacity of Anopheles gambiae Giles mosquitoes in
      malaria transmission, Kenya.
AB  - We investigated the effects of deforestation on microclimates and sporogonic
      development of Plasmodium falciparum parasites in Anopheles gambiae mosquitoes in
      an area of the western Kenyan highland prone to malaria epidemics. An. gambiae
      mosquitoes were fed with P. falciparum-infected blood through membrane feeders.
      Fed mosquitoes were placed in houses in forested and deforested areas in a
      highland area (1,500 m above sea level) and monitored for parasite development.
      Deforested sites had higher temperatures and relative humidities, and the overall
      infection rate of mosquitoes was increased compared with that in forested sites.
      Sporozoites appeared on average 1.1 days earlier in deforested areas. Vectorial
      capacity was estimated to be 77.7% higher in the deforested site than in the
      forested site. We showed that deforestation changes microclimates, leading to
      more rapid sporogonic development of P. falciparum and to a marked increase of
      malaria risk in the western Kenyan highland.

PMID- 18826816
TI  - Ecological factors associated with West Nile virus transmission, northeastern
      United States.
AB  - Since 1999, West Nile virus (WNV) disease has affected the northeastern United
      States. To describe the spatial epidemiology and identify risk factors for
      disease incidence, we analyzed 8 years (1999-2006) of county-based human WNV
      disease surveillance data. Among the 56.6 million residents in 8 northeastern
      states sharing primary enzootic vectors, we found 977 cases. We controlled for
      population density and potential bias from surveillance and spatial proximity.
      Analyses demonstrated significant spatial spreading from 1999 through 2004
      (p<0.01, r2 = 0.16). A significant trend was apparent among increasingly urban
      counties; county quartiles with the least (<38%) forest cover had 4.4-fold
      greater odds (95% confidence interval [CI] 1.4-13.2, p = 0.01) of having above
      median disease incidence (>0.75 cases/100,000 residents) than counties with the
      most (>70%) forest cover. These results quantify urbanization as a risk factor
      for WNV disease incidence and are consistent with knowledge of vector species in
      this area.

PMID- 18826817
TI  - Deaths from norovirus among the elderly, England and Wales.
AB  - The number of deaths in England and Wales associated with gastrointestinal
      pathogens, norovirus in particular, in persons >or=65 years was estimated for
      2001-2006. Regression analysis was used to model monthly counts of
      gastrointestinal pathogens in fecal samples from infected patients against
      monthly counts of deaths from infectious and noninfectious intestinal diseases.
      Data came from the Office of National Statistics (death registrations from local
      registrars) and from the Health Protection Agency (laboratory results). Model
      results suggest that 20% (13.3%-26.8%) of deaths in persons >or=65 years of age
      caused by infectious intestinal disease other than Clostridium difficile were
      associated with norovirus infection in this period and that 13% (7.5%-18.5%) of
      deaths caused by noninfectious intestinal disease were associated with norovirus.
      An estimated 80 deaths each year in this age group may be associated with
      norovirus infection.

PMID- 18826818
TI  - Norwalk virus shedding after experimental human infection.
AB  - Noroviruses are the most common cause of viral gastroenteritis in the United
      States. To determine the magnitude and duration of virus shedding in feces, we
      evaluated persons who had been experimentally infected with Norwalk virus. Of 16
      persons, clinical gastroenteritis (watery diarrhea and/or vomiting) developed in
      11; symptomatic illness lasted 1-2 days. Virus shedding was first detected by
      reverse transcription-PCR (RT-PCR) 18 hours after participant inoculation and
      lasted a median of 28 days after inoculation (range 13-56 days). The median peak
      amount of virus shedding was 95 x 10(9) (range 0.5-1,640 x 10(9)) genomic
      copies/g feces as measured by quantitative RT-PCR. Virus shedding was first
      detected by antigen ELISA approximately 33 hours (median 42 hours) after
      inoculation and lasted 10 days (median 7 days) after inoculation. Understanding
      of the relevance of prolonged fecal norovirus excretion must await the
      development of sensitive methods to measure virus infectivity.

PMID- 18826819
TI  - Prophylaxis after exposure to Coxiella burnetii.
AB  - Coxiella burnetii is a category B bioterrorism agent. We numerically evaluated
      the risks and benefits from postexposure prophylaxis (PEP) after an intentional
      release of C. burnetii to the general population, pregnant women, and other high
      risk populations. For each group, we constructed a decision tree to estimate
      illness and deaths averted by use of PEP/100,000 population. We calculated the
      threshold points at which the number of PEP-related adverse events was equal to
      the cases averted. PEP was defined as doxycycline (100 mg 2x/day for 5 days),
      except for pregnant women, where we assumed a PEP of trimethoprim
      sulfamethoxazole (160 mg/800 mg 2x/day) for the duration of the pregnancy. PEP
      would begin 8-12 days postexposure. On the basis of upper-bound probability
      estimates of PEP-related adverse events for doxycycline, we concluded that the
      risk for Q fever illness outweighs the risk for antimicrobial drug-related
      adverse events when the probability of C. burnetii exposure is >or=7% (pregnant
      women using trimethoprim-sulfamethoxazole = 16%).

PMID- 18826821
TI  - Cryptosporidium species and subtypes and clinical manifestations in children,
      Peru.
AB  - To determine whether clinical manifestations are associated with genotypes or
      subtypes of Cryptosporidium spp., we studied a 4-year longitudinal birth cohort
      of 533 children in Peru. A total of 156 infection episodes were found in 109
      children. Data from first infections showed that C. hominis was associated with
      diarrhea, nausea, vomiting, general malaise, and increased oocyst shedding
      intensity and duration. In contrast, C. parvum, C. meleagridis, C. canis, and C.
      felis were associated with diarrhea only. C. hominis subtype families were
      identified (Ia, Ib, Id, and Ie); all were associated with diarrhea. Ib was also
      associated with nausea, vomiting, and general malaise. All C. parvum specimens
      belonged to subtype family IIc. Analysis of risk factors did not show
      associations with specific Cryptosporidium spp. genotypes or subtypes. These
      findings strongly suggest that Cryptosporidium spp. and subtypes are linked to
      different clinical manifestations in children.

PMID- 18826822
TI  - Endemic and epidemic lineages of Escherichia coli that cause urinary tract
      infections.
AB  - Women with urinary tract infections (UTIs) in California, USA (1999-2001), were
      infected with closely related or indistinguishable strains of Escherichia coli
      (clonal groups), which suggests point source dissemination. We compared strains
      of UTI-causing E. coli in California with strains causing such infections in
      Montreal, Quebec, Canada. Urine specimens from women with community-acquired UTIs
      in Montreal (2006) were cultured for E. coli. Isolates that caused 256
      consecutive episodes of UTI were characterized by antimicrobial drug
      susceptibility profile, enterobacterial repetitive intergenic consensus 2 PCR,
      serotyping, XbaI and NotI pulsed-field gel electrophoresis, multilocus sequence
      typing, and phylogenetic typing. We confirmed the presence of drug-resistant,
      genetically related, and temporally clustered E. coli clonal groups that caused
      community-acquired UTIs in unrelated women in 2 locations and 2 different times.
      Two clonal groups were identified in both locations. Epidemic transmission
      followed by endemic transmission of UTI-causing clonal groups may explain these
      clusters of UTI cases.

PMID- 18826823
TI  - Microbial interactions during upper respiratory tract infections.
AB  - Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and
      Staphylococcus aureus often colonize the nasopharynx. Children are susceptible to
      bacterial infections during or soon after upper respiratory tract infection
      (URI). We describe colonization with these 4 bacteria species alone or in
      combination during URI. Data were from a prospective cohort of healthy children 6
      to 36 months of age followed up for 1 year. Analyses of 968 swabs from 212
      children indicated that S. pneumoniae colonization is negatively associated with
      colonization by H. influenzae. Competitive interactions shifted when H.
      influenzae and M. catarrhalis colonized together. In this situation, the
      likelihood of colonization with all 3 species is higher. Negative associations
      were identified between S. pneumoniae and S. aureus and between H. influenzae and
      S. aureus. Polymicrobial interactions differed by number and species of bacteria
      present. Antimicrobial therapy and vaccination strategies targeting specific
      bacterial species may alter the flora in unforeseen ways.

PMID- 18826824
TI  - Pyogenic liver abscess as endemic disease, Taiwan.
AB  - Pyogenic liver abscess has become a health problem in Taiwanese society. However,
      the extent of this problem has remained unclear because of the lack of a
      population-based study. We therefore performed a nationwide analysis of pyogenic
      liver abscess in Taiwan from 1996 through 2004. We analyzed 29,703 cases from the
      Taiwan National Health Insurance database and 506 cases from National Taiwan
      University Hospital. Our analysis showed that the annual incidence of pyogenic
      liver abscess increased steadily from 11.15/100,000 population in 1996 to
      17.59/100,000 in 2004. Diabetes, malignancy, renal disease, and pneumonia were
      associated with a higher risk for the disease. By contrast, death due to pyogenic
      liver abscess decreased over time, although population-based abscess-related
      death increased slightly. Renal disease, malignancy, pneumonia, and heart disease
      correlated with higher death rates; Klebsiella pneumoniae infection and
      therapeutic procedures were related to lower death rates. Diabetes did not
      significantly change death rates for the 506 patients from the hospital.

PMID- 18826825
TI  - Estimating community incidence of Salmonella, Campylobacter, and Shiga toxin
      producing Escherichia coli infections, Australia.
AB  - To estimate multipliers linking surveillance of salmonellosis,
      campylobacteriosis, and Shiga toxin-producing Escherichia coli (STEC) infections
      to community incidence, we used data from a gastroenteritis survey and other
      sources. Multipliers for severe (bloody stool/long duration) and milder cases
      were estimated from the component probabilities of doctor visit, stool test,
      sensitivity of laboratory test, and reporting to surveillance system. Pathogens
      were classified by the same severity criteria and appropriate multipliers
      applied. Precision of estimates was quantified by using simulation techniques to
      construct 95% credible intervals (CrIs). The multiplier for salmonellosis was
      estimated at 7 (95% CrI 4-16), for campylobacteriosis at 10 (95% CrI 7-22), and
      for STEC at 8 (95% CrI 3-75). Australian annual community incidence rates per
      100,000 population were estimated as 262 (95% CrI 150-624), 1,184 (95% CrI 756
      2,670), and 23 (95% CrI 13-54), respectively. Estimation of multipliers allows
      assessment of the true effects of these diseases and better understanding of
      public health surveillance.

PMID- 18826826
TI  - Automatic outbreak detection algorithm versus electronic reporting system.
AB  - To determine efficacy of automatic outbreak detection algorithms (AODAs), we
      analyzed 3,582 AODA signals and 4,427 reports of outbreaks caused by
      Campylobacter spp. or norovirus during 2005-2006 in Germany. Local health
      departments reported local outbreaks with higher sensitivity and positive
      predictive value than did AODAs.

PMID- 18826827
TI  - Rickettsia typhi and R. felis in rat fleas (Xenopsylla cheopis), Oahu, Hawaii.
AB  - Rickettsia typhi (prevalence 1.9%) and R. felis (prevalence 24.8%) DNA were
      detected in rat fleas (Xenopsylla cheopis) collected from mice on Oahu Island,
      Hawaii. The low prevalence of R. typhi on Oahu suggests that R. felis may be a
      more common cause of rickettsiosis than R. typhi in Hawaii.

PMID- 18826828
TI  - New hosts for equine herpesvirus 9.
AB  - Equine herpesvirus 9 was detected in a polar bear with progressive encephalitis;
      the source was traced to 2 members of a potential equid reservoir species,
      Grevy's zebras. The virus was also found in an aborted Persian onager. Thus, the
      natural host range is extended to 6 species in 3 mammalian orders.

PMID- 18826829
TI  - Extended sequence typing of Campylobacter spp., United Kingdom.
AB  - Supplementing Campylobacter spp. multilocus sequence typing with nucleotide
      sequence typing of 3 antigen genes increased the discriminatory index achieved
      from 0.975 to 0.992 among 620 clinical isolates from Oxfordshire, United Kingdom.
      This enhanced typing scheme enabled identification of clusters and retained data
      required for long-range epidemiologic comparisons of isolates.

PMID- 18826830
TI  - Chikungunya outbreak, South India, 2006.
AB  - We investigated chikungunya outbreaks in South India and observed a high attack
      rate, particularly among adults and women. Transmission was facilitated by Aedes
      aegypti mosquitoes in peridomestic water containers, as indicated by a high
      Breteau index. We recommended vector control measures and health education to
      promote safe water storage practices.

PMID- 18826831
TI  - Control strategy for Echinococcus multilocularis.
AB  - Echinococcus multilocularis, the causative agent of zoonotic alveolar
      echinococcosis, can be controlled effectively by the experimental delivery of
      anthelminthic baits for urban foxes. Monthly baiting over a 45-month period was
      effective for long-lasting control. Trimonthly baiting intervals were far less
      effective and did not prevent parasite recovery.

PMID- 18826832
TI  - Mapping the probability of schistosomiasis and associated uncertainty, West
      Africa.
AB  - We aimed to map the probability of Schistosoma haematobium infection being >50%,
      a threshold for annual mass praziquantel distribution. Parasitologic surveys were
      conducted in Burkina Faso, Mali, and Niger, 2004-2006, and predictions were made
      by using Bayesian geostatistical models. Clusters with >50% probability of having
      >50% prevalence were delineated in each country.

PMID- 18826833
TI  - Spinach-associated Escherichia coli O157:H7 outbreak, Utah and New Mexico, 2006.
AB  - In 2006, Utah and New Mexico health departments investigated a multistate cluster
      of Escherichia coli O157:H7. A case-control study of 22 case-patients found that
      consuming bagged spinach was significantly associated with illness (p<0.01). The
      outbreak strain was isolated from 3 bags of 1 brand of spinach. Nationally, 205
      persons were ill with the outbreak strain.

PMID- 18826834
TI  - Molecular surveillance for multidrug-resistant Plasmodium falciparum, Cambodia.
AB  - We conducted surveillance for multidrug-resistant Plasmodium falciparum in
      Cambodia during 2004-2006 by assessing molecular changes in pfmdr1. The high
      prevalence of isolates with multiple pfmdr1 copies found in western Cambodia near
      the Thai border, where artesunate-mefloquine therapy failures occur, contrasts
      with isolates from eastern Cambodia, where this combination therapy remains
      highly effective.

PMID- 18826835
TI  - Decreased tuberculosis incidence and declining clustered case rates, Madrid.
AB  - To determine effect of recent tuberculosis transmission rates on incidence rates,
      we conducted 2 prospective population-based molecular epidemiologic studies in
      Madrid during 1997-1999 (4% immigrants) and 2002-2004 (14.9% immigrants). Case
      rates decreased in association with declining clustered case rates among Spanish
      born persons. New strains were introduced through immigration.

PMID- 18826836
TI  - Influenza A virus infections in land birds, People's Republic of China.
AB  - Water birds are considered the reservoir for avian influenza viruses. We examined
      this assumption by sampling and real-time reverse transcription-PCR testing of
      939 Asian land birds of 153 species. Influenza A infection was found,
      particularly among migratory species. Surveillance programs for monitoring spread
      of these viruses need to be redesigned.

PMID- 18826837
TI  - Invasive group B streptococcal infections in infants, France.
AB  - Clinical features and molecular characterization of 109 group B streptococci
      causing neonatal invasive infections were determined over an 18-month period in
      France. Sixty-four percent of the strains were from late-onset infections, and
      75% were capsular type III. The hypervirulent clone ST-17 was recovered in 80% of
      meningitis cases.

PMID- 18826838
TI  - Owner valuation of rabies vaccination of dogs, Chad.
AB  - We estimated the association between amount charged and probability that dog
      owners in N'Djamena, Chad, would have their dogs vaccinated against rabies.
      Owners would pay approximately 400-700 CFA francs (US $0.78-$1.36)/animal. To
      vaccinate >or=70% of dogs, and thus interrupt rabies transmission, health
      officials should substantially subsidize these vaccinations.

PMID- 18826839
TI  - Unexplained deaths and critical illnesses of suspected infectious cause, Taiwan,
      2000-2005.
AB  - We report 5 years' surveillance data from the Taiwan Centers for Disease Control
      on unexplained deaths and critical illnesses suspected of being caused by
      infection. A total of 130 cases were reported; the incidence rate was 0.12 per
      100,000 person-years; and infectious causes were identified for 81 cases (62%).

PMID- 18826840
TI  - Murine typhus and febrile illness, Nepal.
AB  - Murine typhus was diagnosed by PCR in 50 (7%) of 756 adults with febrile illness
      seeking treatment at Patan Hospital in Kathmandu, Nepal. Of patients with murine
      typhus, 64% were women, 86% were residents of Kathmandu, and 90% were unwell
      during the winter. No characteristics clearly distinguished typhus patients from
      those with blood culture-positive enteric fever.

PMID- 18826841
TI  - Effects of school closures, 2008 winter influenza season, Hong Kong.
AB  - In winter 2008, kindergartens and primary schools in Hong Kong were closed for 2
      weeks after media coverage indicated that 3 children had died, apparently from
      influenza. We examined prospective influenza surveillance data before, during,
      and after the closure. We did not find a substantial effect on community
      transmission.

PMID- 18826842
TI  - Recent shift in age pattern of dengue hemorrhagic fever, Brazil.

PMID- 18826843
TI  - Confirmed Mycoplasma pneumoniae endocarditis.

PMID- 18826844
TI  - Human rhinovirus group C infection in children with lower respiratory tract
      infection.

PMID- 18826845
TI  - Serogroup A Neisseria meningitidis with reduced susceptibility to ciprofloxacin.

PMID- 18826846
TI  - Identification of all dengue serotypes in Nepal.

PMID- 18826847
TI  - Detecting avian influenza virus (H5N1) in domestic duck feathers.

PMID- 18826848
TI  - Neisseria gonorrhoeae meningitis in pregnant adolescent.

PMID- 18826849
TI  - Echinococcosis and Tibetan communities.

PMID- 18826850
TI  - Re: Resource allocation during an influenza pandemic.

PMID- 18826851
TI  - Collage and assemblage in the microbial world.

PMID- 18826852
TI  - Vitamin D receptor ligand therapy in chronic kidney disease.
AB  - Chronic kidney disease is a growing public health concern, and secondary
      hyperparathyroidism is one of the most serious associated comorbidities. In
      healthy individuals, precisely controlled feedback loops dynamically modulate
      parathyroid hormone (PTH) levels. As kidney function declines, phosphate
      retention, decreased 1a,25-dihydroxyvitamin D3, and a tendency to hypocalcemia
      leads to overstimulation of PTH production and parathyroid hyperplasia. Vitamin D
      receptor (VDR) ligands are essential tools for controlling parathyroid activity.
      This review highlights the current clinical and biochemical VDR ligand studies,
      focusing on the differences between selective and nonselective VDR ligands. It is
      apparent that VDR ligands have important roles in the management of secondary
      hyperparathyroidism. Selective VDR ligands, in particular, may offer additional
      benefits in the treatment of bone disease, and may potentially reduce adverse
      effects related to cardiovascular disease.

PMID- 18826853
TI  - Improvements in renal osteodystrophy in patients treated with lanthanum carbonate
      for two years.
AB  - AIMS: To investigate the evolution of renal osteodystrophy in patients on
      maintenance dialysis, treated with lanthanum carbonate (LC) vs. standard
      phosphate-binder therapy (Stx). MATERIALS AND METHODS: This was a 2-year,
      randomized, prospective, open-label study during which patients on dialysis
      received LC titrated to a maximum of 3,000 mg/day or their previous phosphate
      binder treatment with the aim to achieve target phosphorus levels of < or = 5.9
      mg/dl. Paired bone biopsy samples for histomorphometric analysis were available
      at baseline and 1 year (LC 32, Stx 33), and at baseline and 2 years (LC 32, Stx
      24). RESULTS: With similar phosphorus control, Stx was associated with
      numerically higher serum calcium levels at most visits. Results of osteocalcin
      and bone-specific alkaline phosphatase in LC patients were higher throughout the
      study and correlated with parameters of bone formation; however, the differences
      were not significant. Histological changes in bone turnover and volume were
      analyzed with respect to normal ranges. There was an improvement in bone turnover
      in the LC group, which was significant in the 1-year group, and an improvement in
      bone volume which was significant in the 2-year group. No significant changes in
      bone turnover or bone volume were observed in the Stx groups. In the 2-year LC
      group, 1 patient had osteomalacia at baseline and end of therapy, and a
      mineralization defect developed in 2 other patients. Several possible factors for
      a mineralization defect were present in these patients, but no single cause could
      be clearly identified. Histomorphometric parameters of bone, including formation
      and mineralization, did not correlate with bone lanthanum. No mineralization
      defect was observed in the Stx groups. CONCLUSION: These findings show that
      similar phosphorus control with Stx and LC results in higher bone turnover after
      1 year and higher bone volume after 2 years with LC.

PMID- 18826854
TI  - Bone histomorphometry and biochemical markers of bone turnover in patients with
      chronic kidney disease Stages 3 - 5.
AB  - AIMS: Precise identification of renal osteodystrophy requires bone
      histomorphometry. Several markers of bone turnover may be useful to predict
      classification and severity of renal osteodystrophy, but there are only limited
      data whether these markers correlate with bone histomorphometry. METHODS: In 36
      patients with chronic kidney disease (CKD) Stage 3/4 and in 96 patients with CKD
      Stage 5 bone histomorphometry was performed and renal osteodystrophy was
      classified according to the standardized international nomenclature. Blood
      samples were taken at the time of bone biopsy, stored and analyzed at the end of
      the study. RESULTS: Osteitis fibrosa (OF) was the most frequent histomorphometric
      form, occurred in 47.2% in CKD Stages 3 - 4 and in 61.4% in CKD Stage 5. There
      was no difference in the frequency of adynamic renal bone disease (ARBD). The
      correlation coefficients between bone turnover markers and histomorphometric
      parameters were higher in CKD 5 patients with high bone turnover lesions. The
      predictive value for high versus low/normal bone turnover status was comparable
      for alkaline phosphatase (APH), bone alkaline phosphatase (BAP), pyridinoline
      (Pyd), desoxypyridinoline (Dpyd), tartrat-resistent acid phosphatase (TRAP Vb)
      and parathyroid hormone (PTH) in CKD Stage 5 patients, but was insufficient for
      APH and TRAP Vb in CKD Stage 3 - 4 patients. CONCLUSIONS: Besides parathyroid
      hormone, biochemical parameters of bone turnover provide a moderate
      discrimination and prediction of bone turnover status only in patients with CKD
      Stage 5. Due to a large variability, they are of limited use in predicting the
      histomorphometric type of renal osteodystrophy. Bone histology remains necessary
      for an exact classification of underlying pathology.

PMID- 18826855
TI  - Osteoprotegerin affects the responsiveness of fibroblast growth factor-23 to high
      oral phosphate intake.
AB  - BACKGROUND: Both fibroblast growth factor-23 (FGF-23) and osteoprotegerin (OPG)
      are associated with phosphate metabolism, and are produced by bone tissue.
      METHODS: In order to clarify the influence of bone turnover on phosphate
      metabolism, we examined the response of FGF-23 to an oral phosphate load in 4
      groups of mice (2 OPG knockout (KO) and 2 wild-type (WT) groups) given either a
      high-phosphate diet or a normal diet by performing serum and urinary biochemical
      assays. RESULTS: Although there was no significant difference in serum phosphate/
      calcium levels between the groups, the decrease in tubular reabsorption rate of
      phosphate (%TRP) by oral phosphate load was smaller in the OPG KO mice than in
      the WT mice. FGF-23 level was significantly increased by a high-phosphate diet in
      WT mice, but not in OPG KO mice. However, there was no significant difference of
      intact PTH and calcitriol levels between the OPG KO and WT mice. CONCLUSION:
      Therefore, OPG may play a key role in mediating the response of FGF-23 to an oral
      phosphate load in bone cells.

PMID- 18826856
TI  - Race is a major determinant of secondary hyperparathyroidism in uremic patients:
      comparative study of Blacks and Hispanics.
AB  - BACKGROUND: Racial differences in bone and mineral metabolism are characterized
      by higher circulating intact parathyroid hormone levels (iPTH) in Black vs. White
      patients with end-stage renal disease (ESRD). The susceptibility of Hispanic
      patients to secondary hyperparathyroidism is not known. METHOD: This is a cross
      sectional study that compares bone and mineral parameters of 48 Black and 61
      Hispanic ESRD patients attending a single outpatient hemodialysis center. RESULT:
      The mean iPTH level was significantly higher in Blacks vs. Hispanics, despite
      similar levels of serum bone-specific alkaline phosphatase (BSAP), calcium,
      phosphorus and similar dosages of vitamin D analogs. After adjusting for
      independent variables including age, diabetic status and plasma levels of C
      reactive protein, phosphorus and albumin significant predictors of iPTH were race
      (p < 0.01), gender (p < 0.05), serum calcium (p < 0.05), BSAP (p < 0.0001) and
      doses of vitamin D analogs (p < 0.001). Adjusted predictors of serum BSAP were
      PTH (p < 0.0001), gender (p = 0.01) and serum albumin (p < 0.005), but not race.
      There was no significant difference in serum BSAP between Blacks and Hispanics
      despite 60% higher iPTH levels in Blacks. CONCLUSIONS: Amongst ESRD patients,
      Blacks have higher iPTH levels compared with Hispanics despite similar BSAP
      levels, these finding support the emerging evidence of racial/ethnic differences
      in response of bone to PTH action.

PMID- 18826857
TI  - Converting hemodialysis patients from intravenous paricalcitol to intravenous
      doxercalciferol - a dose equivalency and titration study.
AB  - AIMS: Doxercalciferol and paricalcitol are used to treat hyperparathyroidism in
      chronic kidney disease. This study was conducted to define equivalent dose
      requirements to convert patients from intravenous paricalcitol to intravenous
      doxercalciferol. METHODS: Following a 4-week baseline period using a fixed dose
      of paricalcitol, 42 adult hemodialysis subjects were assigned to receive a fixed
      dose of doxercalciferol for 4 weeks using a conversion factor of either 50 or 65%
      of the prior paricalcitol dose. During a 12-week titration period the
      doxercalciferol dose was adjusted to optimize iPTH levels into the range of 150 -
      300 pg/ml. Annual costs to achieve equivalent iPTH control were calculated for
      both vitamin D analogs. RESULTS: During the doxercalciferol fixed-dose period,
      the average dose of doxercalciferol was 2.1 +/- 1.3 microg and 3.1 +/- 1.8 microg
      in the 50 and 65% dose conversion groups, respectively. During this period mean
      iPTH in the 50% dose conversion group increased by 24 pg/ml (p = 0.017). During
      the dose titration period, doxercalciferol was increased to bring iPTH within the
      target range. Calcium control was maintained with both conversion factors, while
      slightly better phosphorus control was seen in the 65% dose conversion group.
      Annualized treatment cost for doxercalciferol was 28% less expensive per patient
      than paricalcitol. CONCLUSION: Patients can be managed safely and effectively
      with conversion and dose titration from paricalcitol to doxercalciferol. Both
      conversion strategies maintained iPTH at clinically satisfactory levels.
      Furthermore, doxercalciferol therapy resulted in drug acquisition cost-savings.

PMID- 18826858
TI  - Mild-to-moderate renal impairment is associated with platelet activation: a cross
      sectional study.
AB  - The high incidence of cardiovascular disease in patients with moderate renal
      impairment is not fully explained by traditional atherothrombotic risk factors.
      Independently from these factors, blood platelet activation may increase the
      cardiovascular disease risk of patients with mild-to-moderate renal impairment.
      Blood platelet activation has not been studied in nondiabetic patients with mild
      to-moderate renal impairment. Therefore, we measured the extent of platelet
      activation by means of fluorescence cytometry in 93 nondiabetic patients with
      MDRD-estimated creatinine clearance ranging from 13 - 63 ml/min/1.73 m2. As
      platelet activation parameters we used the expression of CD62P (P-selectin), CD
      63 (glycoprotein 53), PAC-1 (activated fibrinogen receptor), CD42b (von
      Willebrand factor receptor) and CD41 (fibrinogen receptor) on the platelet
      surface membrane. The expression of CD62p, CD63 and PAC-1 was statistically
      significantly inversely related to the estimated glomerular filtration rate in
      these patients (standardized b -0.28, -0.32 and -0.39, respectively). We conclude
      that nondiabetic mild-to-moderate renal impairment is associated with blood
      platelet activation. Whether this contributes to the increased cardiovascular
      risk in these patients needs further study.

PMID- 18826859
TI  - Effects of nocturnal oxygen therapy on sleep apnea syndrome in peritoneal
      dialysis patients.
AB  - Sleep apnea syndrome (SAS) is common in patients with end-stage renal disease
      (ESRD). Although the treatment of choice is continuous positive airway pressure
      (CPAP) particularly for obstructive SAS, long-term compliance is not
      satisfactory. We investigated the effectiveness of nocturnal oxygen therapy on
      sleep apnea and autonomic nervous dysfunction in peritoneal dialysis (PD)
      patients with SAS. METHODS: 40 patients on PD in our outpatient clinic were
      screened for SAS by pulse oximetry. We set the indication for nocturnal oxygen
      therapy at 4% oxygen desaturation index (4% ODI; defined as the number of falls
      of oxygen saturation > or = 4% per hour) > 5 or average nocturnal saturation <
      95%. For SAS patients, 2 l per minute of oxygen was given during sleep and
      polysomnography was performed before and 1 month after oxygen administration. The
      heart rate variability was analyzed to assess autonomic nervous activity.
      RESULTS: 23 patients fulfilled the indication for oxygen therapy and 11 patients
      agreed to participate in the study. After oxygen therapy, the apnea-hypopnea
      index (AHI) and the frequencies of hypopnea and central apnea were significantly
      decreased (AHI: from 31.1 +/- 8.8 to 12.7 +/- 8.5, p < 0.01; hypopnea: from 19.5
      +/- 4.3 to 3.5 +/- 3.2, p < 0.01; central apnea: from 4.0 +/- 4.0 to 0.8 +/- 1.2,
      p < 0.05), whereas that of obstructive apnea was not changed. An analysis of
      heart rate variability showed that oxygen therapy did not alter autonomic
      activity after 1 month of oxygen therapy. CONCLUSIONS: Nocturnal oxygen therapy
      decreases hypopnea and central apnea in PD patients with SAS. Nocturnal oxygen
      therapy may be useful for the treatment of SAS in PD patients, particularly when
      central apnea and hypopnea are predominant.

PMID- 18826860
TI  - Early IgG glomerulonephritis recurrence in a kidney transplant recipient.
AB  - We report a second case of mesangial IgG glomerulonephritis recurrence after
      kidney allograft transplantation. Mesangial IgG glomerulonephritis is considered
      a distinct glomerulonephritis. To date, only 1 recurrence after transplantation
      has been reported. In the present case, recurrence occurred 3 months after
      transplantation, following an acute rejection episode. Three sequential graft
      biopsies describe the onset of glomerular lesions.

PMID- 18826861
TI  - Successful treatment of post-MRSA infection glomerulonephritis with steroid
      therapy.
AB  - A 48-year-old man without underlying disease developed mediastinitis and was
      treated by mediastinal drainage. Methicillin-resistant Staphylococcus aureus
      (MRSA) was detected in a culture of the abscess material. He was treated with
      anti-MRSA antibiotics and the MRSA infection improved. Four weeks after the onset
      of MRSA infection, he developed rapidly progressive glomerulonephritis (RPGN)
      with nephrotic syndrome (NS). A renal biopsy showed endocapillary proliferative
      glomerulonephritis with IgA-predominant glomerular deposition. These
      clinicopathological findings were consistent with those in glomerulonephritis
      following MRSA infection (post-MRSA infection glomerulonephritis). The level of
      serum creatinine increased to 6.3 mg/dl, 7 weeks after the onset of RPGN. At that
      time, the eradication of MRSA infection was considered. He was given middle-dose
      steroid therapy. Thereafter, his RPGN with NS improved. MRSA infection did not
      recur. If the disease activity of post-MRSA infection glomerulonephritis persists
      after the disappearance of MRSA infection, the application of immunosuppressive
      therapy with steroids may be useful.

PMID- 18826862
TI  - Hyperkalemia in familial mitochondrial cytopathy.
AB  - AIM: To contribute to understanding the pathogenesis of hyperkalemia that often
      occurs in patients with diabetes. MATERIALS AND METHODS: We describe 3 familial
      cases of mitochondrial diabetes mellitus. The mitochondrial A3243G point mutation
      was confirmed in a mother and her 2 children. We examined their clinical features
      and pathological findings, and assessed heteroplasmy of mutant mitochondria DNA
      (mtDNA) by molecular analysis. RESULTS: The second son had spontaneous
      hyperkalemia and hyporeninemic hypoaldosteronism. Histopathological examination
      revealed severe tubulointerstitial and vascular changes around the
      juxtaglomerular apparatus. The mother only showed intermittent hyperkalemia
      concurrently with the aggravation of heart failure, and the pathological changes
      in her kidneys were mild. Heteroplasmy was more severe in the second son than in
      the mother. CONCLUSION: Heteroplasmy of mitochondrial cytopathy combined with
      diabetes mellitus led to abnormalities resembling those seen in Type IV renal
      tubular acidosis.

PMID- 18826863
TI  - Alternative treatment for systemic involvement in a child with postdiarrheal
      hemolytic-uremic syndrome.

PMID- 18826864
TI  - Effect of HMG CoA reductase inhibitors on low-density lipoprotein cholesterol and
      C-reactive protein: systematic review and meta-analysis.
AB  - OBJECTIVE: HMG CoA reductase inhibitors (statins) have been claimed to decrease C
      reactive protein (CRP), independent of their effect on low-density lipoprotein
      cholesterol (LDL-C). We conducted a systematic review and meta-analysis to
      investigate whether a relationship between the average effect of statins on LDL-C
      and CRP exists. DATA SOURCES: The literature search of the Medline and Cochrane
      databases between 1980 and August 2007 yielded 65 statin intervention studies
      with 94 treatment arms involving 16,260 patients reporting changes in both LDL-C
      and CRP. DATA EXTRACTION AND STATISTICAL METHOD: From each study relative changes
      in LDL-C and CRP were extracted. Random effects meta-analysis was used to obtain
      pooled summary estimates of the average study specific LDL-C and CRP reductions,
      in total and stratified by dose and type of statin. Weighted correlation analysis
      and metaregression analysis was used to investigate the relationship between the
      LDL-C and CRP changes adjusted for baseline values, type of statin and dose.
      RESULTS: Pooled summary estimates of statin-induced changes in LDL-C and CRP
      levels were -34.7% (95% CI: -37.7% to -31.8%) and -30.8% (95% CI: -39.4% to 
      22.3%), respectively. We found a positive correlation between the average LDL-C
      and CRP reduction (r = 0.49, p = 0.010) which increased when adjusting for pre
      treatment concentrations (r = 0.79, p < 0.001). The effect of statins on CRP were
      strongly related to the changes in LDL-C and baseline concentrations, independent
      of the type and dose of statin used. CONCLUSION: Our meta-analysis shows a strong
      correlation between statin-induced reductions in LDL-C and CRP, which has not
      been evident from individual studies. Measuring CRP in addition to LDL-C in the
      monitoring of statin treatment is currently not warranted.

PMID- 18826865
TI  - Influence of grape juice and orange juice on the pharmacokinetics and
      pharmacodynamics of diltiazem in healthy human male subjects.
AB  - OBJECTIVE: The objective was to study the effect of grape juice and orange juice
      on the pharmacokinetics (PK) and pharmacodynamics (PD) of diltiazem in healthy
      human volunteers. METHODOLOGY: The study design was open-label, balanced,
      randomized, 3-period, single-dose and crossover. A group of 12 healthy, adult,
      male human volunteers received a single oral dose of diltiazem 180 mg extended
      release capsule on three different occasions: with 200 ml of water, with 200 ml
      of grape juice and with 200 ml of orange juice in random order. A washout period
      of 7 days was kept between each study period. Serial blood samples were collected
      up to 24 h post dose and assayed for diltiazem using a specific and validated
      HPLC method. Blood pressure (BP) and ECG measurements were done at 0, 1, 2, 3, 4,
      6, 8, 10, 12, 16 and 24 h post dose. Analysis of variance was carried out using
      logarithmic transformations of AUC and Cmax as well as nontransformed tmax.
      RESULTS: No significant change was observed in heart rate and BP. The median tmax
      was identical in all three occasions. The 90% CI of the Cmax ratios for orange
      juice/water were 104.59 - 114.86 and for grape juice/water were 93.91 - 103.13.
      Similarly, the 90% CI of the AUC0-inf ratios for orange juice and grape juice vs.
      water were 103.68 - 119.83 and 88.56 - 104.06, respectively. Since these values
      fall within the bioequivalence criteria of 80 - 120% limits, our study
      demonstrates absence of interaction of diltiazem with grape juice or orange
      juice. CONCLUSIONS: There is no significant influence of grape juice or orange
      juice on the pharmacokinetics and pharmacodynamics of diltiazem.

PMID- 18826866
TI  - Absence of an effect of a single-dose deferasirox on the steady-state
      pharmacokinetics of digoxin.
AB  - Deferasirox (Exjade, ICL670) is a potent iron chelator, recently approved as
      first-line therapy for the treatment of blood-transfusion-related iron overload.
      Iron deposition in the heart may lead to cardiac dysfunction in patients with
      iron overload. Thus, the combination of cardiac glycosides and deferasirox is
      likely to be used in clinical practice. OBJECTIVE: This study was designed to
      investigate the effect of deferasirox on steady-state pharmacokinetics of
      digoxin. As digoxin is a P-glycoprotein substrate, the trial also explored the
      potential of deferasirox to alter the pharmacokinetics of compounds transported
      by P-glycoprotein in general. METHODS: An open-label, randomized, 2-period,
      crossover study was carried out with 16 healthy volunteers. During both treatment
      periods, each subject received daily oral doses of digoxin for 8 days (0.5 mg on
      Day 1 and 0.25 mg/day on Days 2 - 8). In one of these treatment periods, single
      oral deferasirox 20 mg/kg was coadministered with digoxin on Day 8.
      Pharmacokinetic parameters assessed at the end of each treatment period were
      compared using the standard statistical analysis for bioequivalence assessment.
      RESULTS: Deferasirox did not alter the steady-state pharmacokinetics of digoxin.
      The geometric mean ratios and 90% confidence intervals for Cmax and AUCtau of
      digoxin (with/without deferasirox) were 0.93 (0.82 - 1.06) and 0.91 (0.83 -
      1.00), respectively, and thus within the equivalence limits of 0.8 - 1.25. The
      amount of digoxin excreted intact in urine was similarly unaltered by
      coadministration of deferasirox. CONCLUSIONS: This study shows that single-dose
      deferasirox has no effect on steady-state pharmacokinetics of digoxin. Therefore,
      no dose adjustment of digoxin is necessary when deferasirox and digoxin are
      coadministered. The lack of interaction suggests that deferasirox is unlikely to
      interact with P-glycoprotein substrates.

PMID- 18826867
TI  - Evaluating average bioequivalence using methods for high variability drugs: a
      case study.
AB  - The purpose of this study was to determine if different methods for average
      bioequivalence in high variability drugs coincide or not in their conclusions
      when applied to the same dataset, and to discuss the method validity and
      reliability of the conclusions. Different approaches for the evaluation of
      average bioequivalence were applied to the results of a bioavailability trial on
      the diuretic drug Furosemide. These methods included widening the bioequivalence
      limits according to regulatory recommendations, scaling the limits and scaling
      the bioequivalence statistic, jointly with evaluating alternative bioavailability
      measures. The methods to establish the bioequivalence limits were also combined
      with some alternative methods to construct confidence intervals. The decision on
      bioequivalence depends much more on the bioavailability measures than on the
      statistical approach. The reliability of the final decision lies mainly in the
      interpretation of these measures and on the special characteristics of each drug.

PMID- 18826868
TI  - Bioequivalence of oxcarbazepine oral suspension vs. film-coated tablet in healthy
      Chinese male subjects.
AB  - OBJECTIVE: Oxcarbazepine (Trileptal) is an antiepileptic drug used as monotherapy
      or adjunctive therapy in the treatment of partial seizures in adults and
      children. The primary objective of this study was to assess the bioequivalence of
      Trileptal oral suspension formulation vs. the film-coated tablet after single and
      multiple twice-daily administrations in fasted, healthy Chinese male subjects.
      METHODS: This was an open-label, randomized, two-period crossover study in 19
      healthy Chinese male subjects. Treatment periods consisted of a single dose of
      300 mg oxcarbazepine (either oral suspension formulation or film-coated tablet)
      on Day 1, b.i.d. administrations of 300 mg from Day 4 to Day 8 inclusive, and a
      final dose of 300 mg on the morning of Day 9. A 1-week washout period was
      implemented between treatment periods. Plasma levels of 10-monohydroxy derivative
      (MHD), the main metabolite mediating the pharmacologic activity of oxcarbazepine,
      were measured by a validated liquid chromatography tandem mass spectrometry
      method. Bioequivalence was assessed by the MHD areas under the concentration time
      curve (AUCs) and maximum concentrations (Cmax) of the oral suspension vs. the
      film-coated tablet. Safety was evaluated throughout the study. RESULTS: Trileptal
      oral suspension formulation was bioequivalent to film-coated tablet after single
      dose and multiple b.i.d. administrations, as assessed by MHD AUCs and Cmax. The
      90% confidence intervals (CI) of the geometric mean of the MHD individual ratios
      were within the bioequivalence CI limits (0.80 - 1.25). No safety concerns were
      raised. CONCLUSIONS: Trileptal oral suspension formulation and film-coated
      tablets are bioequivalent in healthy Chinese males.

PMID- 18826869
TI  - [No psychiatry without social psychiatry].

PMID- 18826870
TI  - [Therapy of Alzheimer's disease: current status and future development].
AB  - Cholinesterase inhibitors and memantine can slow the course of Alzheimer's
      disease. In Austria the frequency of treatment is in the upper third among
      countries of the EU. Yet, the majority of Alzheimer patients does not receive
      adequate medication. Compliance to treatment is low. Studies on cholinesterase
      inhibitors show that only one third and one fifth of patients adhere to
      medication after 3 months and 12 months, respectively. Causes for low compliance
      are only partly patient-related, many factors are system-inherent. Knowledge of
      these factors is a pre-requisite for the treating physician to improve current
      unfavourable situation. Present treatment strategies are symptomatic, causal
      disease-modifying therapies are urgently needed. Research activity in the field
      is high and dominated by the amyloid hypothesis. We here review the basis and
      recent studies on secretase-inhibitors, immunization, aggregation of Abeta,
      statins and PPARgamma-agonists. Research towards strategies against tau-pathology
      is less dominant and focuses on inhibition of kinases and increase of activity of
      phosphatases. Causal therapies would have great effects on a population basis
      even if efficacy is only moderate. A disease-modifying therapy which delays the
      onset of Alzheimer disease by 5 years, will probably reduce the number of
      patients by nearly 50% during the next 50 years.

PMID- 18826871
TI  - [The acceptance of suicide motives--a key for understanding the differences of
      national suicide rates?].
AB  - National suicide rates differ to a high extent. Tentative explanations for this
      finding reach from macro-social to population-genetic models. Still unexplored is
      the influence of cultural values, i.e. the association between the acceptance of
      suicide motives in a population and the national suicide rates. The goal of this
      study was the development and evaluation of a questionnaire on the acceptance of
      suicide motives (ASM), an instrument which will be used for transcultural
      psychiatric research in a multi-centre study. Additionally the first results of a
      trial with 153 healthy Austrians are presented. Test-Retest reliability of the
      five scales ranged from r=0.74 after to r=0.89 for 3 months interval. The
      internal consistency of scales was very good (Cronbachs Alpha 0.71 after to
      0.88). The Austrians especially accept motives associated with physical frailty
      or guilt feelings and less those associated with shame. The acceptance of suicide
      motives relatively stable in terms of age and gender. Thus, the ASM seems to be
      suited as an instrument for cultural comparative studies on the detection of
      reasons of national suicide rates.

PMID- 18826872
TI  - [Prevalence of psychiatric disorders among homeless adolescents].
AB  - Various studies show a high prevalence of mental disorders among homeless people.
      So far most of these studies deal solely with single men, mainly affected by
      homelessness. Few data exist for women, children, adolescents and whole families
      that are more and more affected by poverty and homelessness. This study,
      conducted in Innsbruck/Austria, determined the prevalence of psychiatric
      disorders among homeless adolescents. The adolescents were recruited in a
      counselling centre and homeless shelter specifically founded for homeless youth.
      Mental disorders were diagnosed with the Structured Clinical Interview for DSM-IV
      (SKID-I). 40 adolescents and young adults ranging from 14-23 years (mean 17.9
      years) were included in the study. The results show that 58% of the homeless
      adolescents were exposed to continuous violence in their families and that
      violence was a major reason for them to leave home. The overall prevalence of
      diagnosed psychiatric disorders was 80% in the whole sample; the leading disorder
      was substance abuse/dependence (65%), followed by mood disorders (42.5%), anxiety
      disorders (17.5%) and eating disorders (17.5%). 57.5% of the adolescents had a
      history of self-harm and 25% reported at least one suicide attempt. Duration of
      homelessness had the greatest influence on the prevalence of mental disorders.
      Longer duration of homelessness was associated with a higher risk of psychiatric
      disorder or self-harm. These results demonstrate the urgent need for early
      psychosocial and psychiatric help for homeless adolescents.

PMID- 18826873
TI  - [Treatment outcome of psychodynamic trauma therapy in an inpatient setting].
AB  - OBJECTIVE: Chronic traumatization with the beginning in childhood may result in a
      number of additional problems not included in the diagnosis of Posttraumatic
      Stress Disorder (PTSD). The efficacy of a three-stage psychodynamically oriented
      inpatient treatment program (PITT) and the role of chronic childhood threat on
      treatment outcome was investigated. METHODS: A six-week treatment group of 84
      inpatients were compared with 43 wait-list controls with "treatment as usual"
      (outpatient psychotherapy or psychiatric treatment in the meanwhile). Using
      measures on PTSD, dissociation, depression, selfsoothing, anxiety and
      somatization, assessments were made at admission, at discharge and 6 months
      postdischarge. Assessments for the outpatient control group were made at
      comparable time spans. RESULTS: In the treatment group significant improvements
      emerged on all investigated parameters (depression, intrusion, avoidance,
      anxiety, somatization, and self-soothing) from baseline to discharge, many of
      which could be maintained over a period for 6 months. PITT especially supports
      the stabilization of patients with experiences of childhood chronic threat and
      insecure attachment. Gains in depression, anxiety, somatization, and self
      soothing were also significant in comparison to the control group. CONCLUSIONS:
      Our results suggest that PITT offered on an inpatient basis is an effective
      treatment for severely traumatized patients that gives impetus to change which
      should be supplemented with further trauma-specific outpatient therapy to
      stabilize gains.

PMID- 18826874
TI  - [Psychiatry and the assessment of human destructiveness: on the question of
      drawing the line between the "normal" concept of evil and psychiatric illnesses].
AB  - Every culture in this world demands that its members comply with a few basic
      rules: Respect for and maintenance of the health and life of others are
      recognised as worldwide ethical norms just as much as consideration for the
      economic basis of existence of others. When these are exceeded, they are punished
      in all social systems. If there is no severe mental disturbance, the
      responsibility for a crime or for socially damaging or non-conformist behaviour
      lies with the individual himself. The question, whether a person could have acted
      differently in a defined situation on the basis of his personality
      characteristics and his neural constitution, leads to diverse answers. Is anti
      social, criminal behaviour a "disturbance in itself" or the result of a
      personality structure which has been defined as an illness or an organic deficit?
      The widest branches of science are occupied with this topic: psychiatry,
      psychology and philosophy, neural sciences and sociology, jurisprudence and
      ethics. The list could be continued. The results of personality research along
      with findings concerning neural mis-connections and the discourse regarding free
      will in contrast to deterministic interpretations are undoubtedly of particular
      relevance. On the basis of research results from the scientific disciplines
      mentioned above, the author concludes that people with socially damaging or
      radically "evil" behaviour are a very heterogeneous group with strongly varying
      personality profiles, unfavourable family socialisation conditions and often
      varied neuro-physiological disturbances, but that responsibility for the crimes
      they are accused of lies with them as long as their disposition and discretion
      capacity has not been impaired or removed through serious psychiatric
      illness.Without classifying them as patients, as our fellow citizens, they
      deserve our due care and recognition of their human dignity.

PMID- 18826875
TI  - ["Homo neurobiologicus"--anthropological concepts in modern psychiatry].
AB  - The workings of the human brain can now be studied with a large arsenal of modern
      technical tools which lead us far beyond traditional realms of philosophical self
      reflection and conventional experimental psychology. The black box of the human
      mind has become illuminated with the following consequences: (1) diagnosis and
      monitoring of mental and neurological diseases have improved significantly; and
      (2) early interpretations of the brain's workings as we can now see it, influence
      the way we think and feel about ourselves. They form an inevitable part of modern
      anthropology, particularly in its applied forms, e.g. psychiatry and
      psychotherapy. Conservative branches of human studies may be appalled by nimble
      neuroscientists who suddenly claim superior evidence and authority. It is an open
      question whether these schools of traditional and of revolutionary data
      acquisition and thought will find a common language which can also be translated
      into clinically useful concepts.

PMID- 18826876
TI  - ESC guidelines for the diagnosis and treatment of acute and chronic heart failure
      2008: the Task Force for the diagnosis and treatment of acute and chronic heart
      failure 2008 of the European Society of Cardiology. Developed in collaboration
      with the Heart Failure Association of the ESC (HFA) and endorsed by the European
      Society of Intensive Care Medicine (ESICM).

PMID- 18826877
TI  - Editorial: Some notes on the politics of occupational medicine.

PMID- 18826878
TI  - Occupational medicine and the construction of "difficult reputations".
AB  - The creation of "difficult reputations" is a collective act of disparagement
      often undertaken to diminish the influence of the target individual or group for
      political reasons. This process can be observed in efforts to discredit the field
      of occupational medicine and the American College of Occupational and
      Environmental Medicine (ACOEM) by revising its history. Examples are given from
      Draper's 'The Company Doctor: Risk, Responsibility, and Corporate
      Professionalism' and LaDou, in which new sources of historical information do not
      support the allegations or impressions conveyed. This tendency is inimical to
      progress in occupational health in general and may be highly destructive to the
      field if not recognized and discouraged.

PMID- 18826879
TI  - Difficult reputations and the social reality of occupational medicine.
AB  - This response to Tee Guidotti's (2008) critique of Elaine Draper's 'The Company
      Doctor: Risk, Responsibility, and Corporate Professionalism' (2003) argues that a
      forthright examination of the conflicts of those working in the field of
      occupational medicine is essential to maintaining the health of the profession
      and to promoting constructive policies. Research for 'The Company Doctor' reveals
      how doctors walk a tightrope of professional demands on them. The author
      describes how corporate employment affects medicine and science and how
      professionals working in corporations are subject to the decisions of company
      managers and to economic and legal imperatives stemming from their status as
      corporate employees. Analyzing company doctors' role in confronting toxics and
      responding to liability fears in corporations, the author argues that problems of
      lost credibility, stigmatization, and tarnished reputation that company doctors
      describe largely stem from the organizational constraints, economic interests,
      and other aspects of the social context of their work. These social forces exert
      powerful pressure on the ethical framework and daily work lives of these
      professionals as well as on the reputation of their field. The author discusses
      ways in which the conflicting demands from being both a corporate employee and a
      physician are a social and structural problem beyond individual ethics.

PMID- 18826880
TI  - Beyond reputation: debate on the role of corporate influence in occupational and
      environmental medicine.
AB  - In his article in this issue, Tee Guidotti casts recent works addressing
      corporate influence on occupational medicine as "collective act[s] of
      disparagement ... undertaken ... for political reasons." We move beyond the
      question of reputation to address key conflicts in the history of occupational
      medicine, including the American Occupational Medical Association's historical
      role in weakening the beryllium standard and the American College of Occupational
      and Environmental Medicine's recent efforts to limit the extent of the Family
      Medical Leave Act. The corporate practice of externalizing health and safety
      costs makes industry influence an important ongoing topic of debate in
      occupational and environmental medicine.

PMID- 18826881
TI  - "Guidotti fails to convince" on two issues.
AB  - This is a response to Tee Guidotti's defense of the American College of
      Occupational and Environmental Medicine (ACOEM) as an ally for workers struggling
      for safer and healthier work. Guidotti fails to convince on two central issues: a
      blindness to the powerful impact of corporate power on professional thought and
      behavior; and a lack of evidence that ACOEM has ever been inclined to collaborate
      with workers. In addition, Guidotti relies upon his own review of ACOEM's
      historical archive to support his argument. Unfortunately, access to this archive
      is limited to those deemed reliable by Guidotti, giving the appearance of an
      attempt to control both information and interpretation, and calling Guidotti's
      own "objectivity" into question.

PMID- 18826882
TI  - Protecting disaster site, support, and recovery workers.
AB  - When a disaster strikes, FEMA activates the worker safety and health provisions
      (annex document) of the National Response Plan (NRP). The annex describes actions
      needed to ensure that threats to safety and health are recognized, evaluated, and
      controlled consistently so that responders are properly protected during incident
      management operations. The activation of the Worker Safety and Health Annex gives
      the Occupational Safety and Health Administration (OSHA) the responsibility to
      coordinate a comprehensive response involving federal, state, and local agencies
      and private-sector organizations to ensure the safety and health needs of
      responders are met. There is confusion, however, as to whether OSHA is acting as
      an advisory "coordinator" or as an enforcement agency. OSHA personnel at the WTC
      and the Gulf region reported they were not clear what role they must perform (and
      the language in the National Response Plan is not explicit). Thus, the need for a
      clear and comprehensive mandatory program.

PMID- 18826883
TI  - Toward tomorrow.

PMID- 18826884
TI  - Open letter about proposed changes for UNC-SPH-"don't lose the mission".

PMID- 18826885
TI  - Asbestos disease in Australia: looking forward and looking back.
AB  - This article provides an overview and analysis of recent developments in policy
      and practice in relation to asbestos disease in Australia. It complements three
      other concurrent publications in this issue representing important contributions
      of people and organizations toward addressing the health and social impacts of
      Australia's asbestos disease epidemic. The campaign to "Make James Hardie Pay" as
      well as the efforts of workers and advocates are profiled in this article as well
      as in this issue's Documents and Voices sections. Discussion of recent
      developments in asbestos-related disease research and mesothelioma surveillance
      is followed by articulation of the comprehensive public and social health
      response that is needed to fully engage and address the asbestos disease legacy
      and to apply lessons learned to help revive the currently waning societal
      commitment to occupational health and safety in Australia and elsewhere.

PMID- 18826886
TI  - The Latrobe Valley: perspectives on asbestos issues.
AB  - The texts of two public addresses by a community advocate, Vicki Hamilton, and
      former asbestos worker, Geoff Swayn, are profiled in this issue's Voices section.
      Each articulates, in their own words, the need for continuing efforts to address
      the health and social impacts of Australia's ongoing asbestos disease epidemic,
      including the need for healing at the community and societal levels that parallel
      the needs of affected individuals and families. Their messages are relevant to
      similarly affected communities and societies internationally, particularly in
      relation to the need to reinvigorate societal commitment to occupational health
      and safety in Australia and elsewhere.

PMID- 18826887
TI  - "Make history but don't forget the past".

PMID- 18826888
TI  - James Hardie asbestos victims compensation summary.

PMID- 18826889
TI  - Is OSHA working for working people?

PMID- 18826892
TI  - Migraine-preventive medications: ensuring their appropriate use.
AB  - OBJECTIVES: To emphasize the magnitude and burden of migraine, the need for
      greater use of migraine-preventive medications in patients who could most benefit
      from them, and the role that pharmacists can play in migraine prevention. DATA
      SOURCES: PubMed and Medline-based literature searches were conducted to determine
      the need for migraine-preventive medications, the treatment of migraine, and how
      pharmacists can assist patients in preventing and treating migraines. The
      literature search included articles from the previous 6 years, as well as earlier
      articles for historical perspective. DATA SYNTHESIS: Migraine is a prevalent,
      chronic, neurologic condition that imposes substantial disability on affected
      patients, leading to a poor quality of life. However, migraine remains
      underrecognized, underdiagnosed, and under- or suboptimally treated. In
      particular, migraine-preventive medications are greatly underused, which
      contributes to avoidable disability. Community pharmacists can play important
      roles in identifying these and other patients with headache who are in need of
      medical care, referring appropriate patients to a health care provider, and
      educating and counseling patients with respect to abortive and preventive
      medications. CONCLUSION: Pharmacists are in a unique position to assist in
      migraine management, particularly with regard to migraine-preventive medications,
      because many patients may not be familiar with the benefits and use of these
      agents. Pharmacist involvement can have a measurable effect on patient care and
      improve the lives of migraine patients.

PMID- 18826893
TI  - Caring for patients with celiac disease: the role of the pharmacist.
AB  - OBJECTIVE: To review the epidemiology, pathophysiology, diagnosis, treatment, and
      complications of celiac disease, in order to provide guidance to pharmacists.
      DATA SOURCES: Published articles identified through Medline using search terms
      such as celiac disease, gluten sensitivity, and gluten enteropathy. Additional
      resources were identified from personal bibliographies collected by the authors
      and bibliographies from gathered articles. DATA SYNTHESIS: Celiac disease is an
      autoimmune disorder that is characterized by intolerance to gluten and affects
      approximately 3 million Americans. Although the most common manifestations of the
      disease are gastrointestinal, including diarrhea, steatorrhea, and weight loss,
      the disease is a multisystem disorder. Malabsorption is common, often leading to
      vitamin and mineral deficiencies and resulting in anemia and osteoporosis.
      Diagnosis is initiated through serology testing and confirmed by intestinal
      biopsy. The only treatment for celiac disease is strict, lifelong adherence to a
      gluten-free diet, which includes avoidance of foods, prescription and
      nonprescription pharmaceutical products, and cosmetics containing wheat, barley,
      and rye. Adherence to the gluten-free diet will promote intestinal healing and
      symptom relief and usually prevent complications of celiac disease. CONCLUSION:
      Pharmacists can play an important role by identifying patients who may have
      celiac disease, providing information for gluten-free foods and pharmaceutical
      products, and encouraging adherence to the gluten-free diet.

PMID- 18826894
TI  - Certification of pharmacy technicians.

PMID- 18826897
TI  - A vision for a healthier future: we must not rest until patient-centered care is
      a reality for all Americans.

PMID- 18826898
TI  - Exploring trends and determinants of pharmacist wage rates: evidence from the
      2000 and 2004 National Pharmacist Workforce Survey.
AB  - OBJECTIVES: To examine pharmacists' hourly wage rates, growth rates in
      pharmacists' wage rates, and factors associated with pharmacists' wage rates in
      2000 and 2004. DESIGN: Descriptive, non-experimental, cross-sectional study.
      SETTING: United States. PARTICIPANTS: 1,644 and 1,129 pharmacists from the 2000
      and 2004 National Pharmacist Workforce Survey, respectively. INTERVENTIONS:
      Secondary data from surveys of pharmacists were analyzed. MAIN OUTCOME MEASURES:
      Pharmacists' wage rates in 2000 and 2004 and growth rates in wage rates between
      2000 and 2004. RESULTS: Wage rates for pharmacists, expressed in 2004 dollars,
      increased 4.9% per year between 2000 and 2004, suggesting real wage growth for
      pharmacists. In 2004, wage rates for pharmacists working part-time were $1.56
      (3.4%) less than wages for pharmacists working full-time. In 2004, pharmacists
      who reported spending higher amounts of time in patient care activities earned
      significantly lower wages. In 2000 and 2004, wage rates were significantly less
      in independently owned pharmacies compared with all other practice settings. In
      2004, women pharmacists earned significantly less per hour (4.9%) compared with
      men pharmacists. CONCLUSION: Pharmacists experienced real wage growth between
      2000 and 2004, which reflects the excess demand for pharmacists. The location of
      pharmacists' employment and the tasks performed by pharmacists in their jobs
      affect wage rates.

PMID- 18826899
TI  - Characteristics of unmet demand for pharmacists: a survey of rural community
      pharmacies in Wisconsin.
AB  - OBJECTIVES: To measure and describe the level of unmet demand for pharmacists in
      rural Wisconsin community pharmacies and to examine determinants of the level of
      unmet demand in these pharmacies. DESIGN: Cross-sectional descriptive study.
      SETTING: Community pharmacies (n = 279) located in rural Wisconsin counties in
      fall 2005. PARTICIPANTS: Key informants (managers/owners) identified for all
      sampled pharmacies. INTERVENTIONS: A one-page participation form and an eight
      page survey instrument were used to collect primary data about the level of unmet
      demand for pharmacists and internal pharmacy factors. Secondary data sources were
      used to extract information on external pharmacy factors. MAIN OUTCOME MEASURES:
      Presence of pharmacist vacancy, number of full-time equivalent (FTE) pharmacist
      positions vacant, and vacancy rate. Internal pharmacy characteristics included
      wage, prescription volume, prescription workload/pharmacist, dispensing-aiding
      technologies, technicians per pharmacist, practice setting, pharmacist FTE
      requirement, and pharmacist satisfaction. External pharmacy characteristics
      included population per pharmacy, seniors per pharmacy, per capita income, and
      rurality. The internal and external pharmacy characteristics were regressed on
      whether a vacancy was present and the vacancy rate (percentage of pharmacist FTEs
      unfilled). RESULTS: Overall response rate to the survey was 43.9%. One-third of
      the respondent pharmacy sites reported a pharmacist vacancy, most often 1.0 or
      less FTE. Pharmacist FTE requirement had a significant positive association with
      the presence of any pharmacist vacancy at a site. Prescription workload per
      pharmacist was positively related to the vacancy rate, while daily prescription
      volume and pharmacist satisfaction were negatively related to the vacancy rate.
      CONCLUSION: Overall, for rural community pharmacies in Wisconsin, a greater need
      for pharmacists at a site appears to make that site more likely to have a
      pharmacist vacancy. Pharmacist vacancies appear to have a greater impact on
      pharmacies that have a lower number of FTE pharmacist positions compared with
      pharmacies with higher FTE pharmacists because, potentially, fewer pharmacists
      are present to redistribute the workload.

PMID- 18826900
TI  - Factors affecting job and career satisfaction among community pharmacists: a
      structural equation modeling approach.
AB  - OBJECTIVES: To investigate the effects of continuing pharmacy education (CPE),
      preceptorship, and the relationship between intrinsic and extrinsic factors
      affecting job and career satisfaction. DESIGN: Cross-sectional study. SETTING:
      Two grocery store pharmacy chains located in Indiana between May 2002 and
      February 2004. PARTICIPANTS: 108 community pharmacists. INTERVENTION: Self
      administered survey. MAIN OUTCOME MEASURES: Structural equation modeling was used
      to determine the effects of intrinsic and extrinsic factors, perceived benefits
      of CPE, advanced training, and being a preceptor on community pharmacists' job
      and career satisfaction. RESULTS: Job satisfaction predicted career satisfaction
      (regression weight 0.49, P = 0.007). The final model comprised extrinsic factors
      only (regression coefficient = 0.897, P = 0.013) with reasonable-fit indices (X2
      ratio = 1.38, root mean square error of approximation = 0.07 [90% CI 0.05-0.09],
      Bentler comparative fit index 0.915). Intrinsic factors were omitted because of
      insignificant regression weight (B) in the initial model (B = 0.24, P = 0.278).
      CPE and preceptorship provided significantly positive effects on extrinsic
      factors, with coefficients of 0.30 (P = 0.029) and 0.27 (P = 0.027),
      respectively. While perceived value of being a preceptor contributed
      significantly to extrinsic factors related to job satisfaction, it was associated
      with a negative impact on career satisfaction (B = -0.41, P = 0.005). Advanced
      training had a negative impact on career satisfaction (B = -0.21, P = 0.114).
      CONCLUSION: Job and career satisfaction are significantly influenced by extrinsic
      factors and may increase when pharmacists enroll in CPE programs and/or precept
      students. Pharmacists may engage in precepting in an attempt to increase job
      satisfaction. Further research in this area is needed.

PMID- 18826901
TI  - Outcome and self-efficacy expectations for medication management of patients with
      diabetes: influence of the pharmacist-patient relationship.
AB  - OBJECTIVE: To examine how outcome and self-efficacy expectations for medication
      management and self-monitoring of patients with diabetes vary by different
      indicators of a pharmacist-patient relationship. DESIGN: Cross-sectional
      descriptive study. SETTING: United States during late 2004. PARTICIPANTS: 568
      noninstitutionalized adults (age > or = 18 years) with type 1 or type 2 diabetes
      who use at least one antidiabetic medication. INTERVENTION: Self-administered
      mail survey. MAIN OUTCOME MEASURES: Outcome and self-efficacy expectations for
      medication management and self-monitoring and pharmacist-patient relationship
      indicators. RESULTS: The adjusted response rate was 60.6% (568 of 937).
      Respondents had differing mean self-efficacy expectation scores (F = 7.82, P <
      0.001) across knowing the pharmacist to varying degrees, and mean self-efficacy
      expectation scores were slightly higher for those who consult with a pharmacist
      to learn about antidiabetic medications (t = -2.41, P = 0.02) compared with those
      who do not. Relationship quality was correlated with both self-efficacy (r =
      0.17, P < 0.000) and outcome expectation (r= 0.11, P = 0.02) scales. Self
      efficacy expectations were higher for those scoring in the upper third of the
      pharmacist-patient relationship index compared with those in the lower third (t =
      -2.79, P = 0.006). CONCLUSION: Descriptive results support some association
      between the pharmacist-patient relationship and self-efficacy expectations,
      although whether this association lies in pharmacists providing education, social
      support, or both is not clear. Further research is needed to investigate this
      association to better elucidate the potential contribution of a pharmacist
      patient relationship to patients' diabetes self-management. The pharmacist
      patient relationship index developed for this study appears to provide a more
      comprehensive and sensitive measure compared with other indices, suggesting
      potential utility in future studies.

PMID- 18826902
TI  - Community pharmacists' knowledge of and attitudes toward oral chemotherapy.
AB  - OBJECTIVE: To assess community pharmacists' attitude toward and knowledge of oral
      chemotherapy (OC) in terms of drug indications, general dosing principles, drug
      interactions, adverse effects, and special handling precautions. DESIGN:
      Descriptive, nonexperimental, cross-sectional survey. SETTING: Colorado, Kansas,
      and the southeastern United States in May and June 2005. PARTICIPANTS: 1,080
      pharmacists in four divisions of a large community pharmacy chain. INTERVENTIONS:
      Web-based survey. MAIN OUTCOME MEASURES: Pharmacist knowledge of and attitude
      toward OC. RESULTS: 243 surveys were returned (response rate 22.5%). Overall,
      pharmacists answered 49.7% of knowledge questions correctly. Pharmacists were
      most knowledgeable about general dosing principles (69%) and least knowledgeable
      about adverse effects (45%) and special handling (25%) of OC. Higher scores were
      seen for pharmacists who dispensed a greater number of OC prescriptions.
      Percentages of correct responses did not vary based on years of experience or
      number of OC continuing pharmacy education (CPE) programs attended. On a Likert
      type scale of 1 (low) to 5 (high), the average comfort in dispensing OC was 2.4.
      On average, pharmacists indicated that knowing about OC was important to their
      practice (3.7) and expressed interest in participating in additional CPE programs
      on OC (4.2). Of respondents, 94.7% indicated that their pharmacy did not have a
      counting tray devoted to cytotoxic drugs. CONCLUSION: This survey identified
      several areas in which pharmacists' knowledge of OC could be enhanced. Handling
      of OC is an area of important need, given the low number of pharmacists reporting
      separate counting trays for cytotoxic drugs.

PMID- 18826903
TI  - Reliability testing of a case-leveling framework for assigning level of
      difficulty of pharmacist's initial patient medication assessments.
AB  - OBJECTIVE: To develop and test the reliability of a case-leveling framework for
      assigning level of difficulty of the pharmacist's task for initial medication
      assessments conducted by pharmacists integrated into family physician offices.
      DESIGN: Descriptive study. SETTING: Seven family practice sites in Ontario from
      June 2004 to July 2006. PATIENTS: Patients referred by their family physician for
      pharmacist assessment. INTERVENTION: Individual medication assessments,
      monitoring, and follow-up by pharmacists. A case-leveling framework was developed
      with three levels of complexity (graded as I, II, or III) including specific
      descriptors and practice-based examples. Reliability was assessed between two
      standardized assessors and between one assessor and project pharmacists. Project
      pharmacist feedback was elicited through an e-mail survey. Reliability is
      reported using the kappa statistic. MAIN OUTCOME MEASURES: Reliability of a case
      leveling framework and helpfulness of the framework as reported by pharmacists.
      RESULTS: 53 patient cases were evaluated for interrater reliability between
      standardized assessors. The mean (+/- SD) case level assigned was 1.8 +/- 0.68,
      and the kappa was 0.62 (95% CI 0.44-0.79), indicating a substantial strength of
      agreement between raters. For the second reliability test, 52 cases were rated,
      with a level of agreement between project pharmacists and the external assessor
      of 0.46 (95% CI 0.27-0.65), indicating moderate agreement. Feedback resulted in
      slight revisions to the original framework. CONCLUSION: The case-leveling
      framework was a reliable method and can be used to determine the level of
      difficulty of patient cases in primary care.

PMID- 18826904
TI  - Perceptions of Medicare Part D enrollees about pharmacists and their role as
      providers of medication therapy management.
AB  - OBJECTIVE: To explore the awareness of Medicare Part D enrollees regarding
      medication therapy management (MTM) and to examine their expectations and
      perceptions of pharmacists in providing MTM. METHODS: The Internet-based survey
      consisted of questions on respondent demographics, prescription-related behavior,
      awareness of MTM, and expectation and perception of pharmacists in usual roles
      and as MTM providers. Four open-ended questions examined expectations, trust,
      source of MTM information, and perceived benefit from MTM. RESULTS: The sample of
      504 Medicare Part D enrollees from California (mean age 72 years) used an average
      of 4.3 prescriptions per day. Awareness of MTM was low in this cohort (93%
      unaware). Trust in the pharmacist was centered on dispensing prescriptions.
      Expectation of pharmacists also revolved around product (>60%). Approximately 70%
      of respondents did not believe they needed MTM; however, 58% believed pharmacists
      were good candidates to provide MTM. Willingness to pay for MTM services was also
      low (31%). CONCLUSION: Medicare Part D enrollees' expectation and perception of
      pharmacists revolves around the dispensing function. The public, payers, and
      policy makers need to be educated to recognize and use pharmacists as cost
      effective providers of MTM.

PMID- 18826905
TI  - Columbus Air Force Base medication profile intervention practice innovation.
AB  - OBJECTIVE: To determine whether community pharmacist-initiated interventions
      containing a recommendation to adjust prescribed medication therapy and delivered
      via fax are viewed as helpful by prescribers and to what extent prescribers
      accept those recommendations. DESIGN: Cross-sectional. SETTING: Columbus Air
      Force Base (Columbus, MS) during a 3-month period in August through October 2007.
      PARTICIPANTS: 57 patient profiles were reviewed by pharmacy staff. INTERVENTION:
      Pharmacy staff evaluated patient profiles with eight or more active medications
      for drug interactions, therapeutic duplications, ability to simplify complex drug
      regimens, and opportunities for additional therapy. After reviewing a patient
      profile, the pharmacist completed a medication management report, noted any
      recommendations about medication therapy, and faxed the report to the patient's
      primary care provider. Physicians were asked to return a form detailing their
      response to the medication management report. MAIN OUTCOME MEASURE: Whether
      pharmacist recommendations were deemed helpful by prescribers in making clinical
      decisions. Secondary outcome measures included the degree to which prescribers
      accepted pharmacist recommendations and how quickly providers responded to
      pharmacist recommendations. RESULTS: The pharmacist-initiated medication
      management fax had a 64.9% response rate from prescribers and was considered
      helpful by 97.3% of prescribers who returned the form to the pharmacist. In
      addition, the majority of prescribers stated via the form that they would address
      the pharmacist's concerns at the next patient visit or call and schedule an
      appointment with the patient. CONCLUSION: As this initiative continues and grows,
      prescribers will be more aware of the medication management fax form program and,
      theoretically, will be more likely to respond to pharmacist recommendations.

PMID- 18826906
TI  - Systematic review and meta-analysis of combination therapy for smoking cessation.
AB  - OBJECTIVES: To review published clinical trials on combination therapy for
      smoking cessation and determine the role of this regimen for treating tobacco
      dependence. DATA SOURCES: Search terms included in this systematic review were
      nicotine replacement patch, nicotine replacement therapy, nicotine replacement
      gum, nicotine replacement inhaler, nicotine replacement nasal spray, nicotine
      replacement lozenge, bupropion SR (for sustained release), combination therapy,
      smoking cessation, and varenicline. Trials conducted from 1994 through October
      10, 2007, were identified using EBM Reviews: Cochrane Central Register of
      Controlled Trials and Medline. STUDY SELECTION: Clinical trials of various
      regimens for smoking cessation were included based on a large sample size (n > or
      = 200); use of first-line smoking cessation therapies; double-blind, randomized,
      placebo-controlled design; and study duration of 1 year or more. The primary
      objective of the included clinical trials was to assess the efficacy of
      combination therapy. Studies that involved medications other than first-line
      therapies, adolescents, and post hoc analyses and that were not written in
      English were excluded. DATA SYNTHESIS: Five clinical trials meeting the inclusion
      criteria were reviewed. All of the studies included the use of the nicotine
      replacement patch along with one other agent. A total of 2,204 patients were
      treated. Combination therapy was significantly better than monotherapy at all
      pooled comparisons (P < 0.05). The aggregated relative risk of abstinence
      comparing combination with single treatment groups was 1.42 (95% CI 1.21-1.67),
      1.54 (1.19-2.00), and 1.58 (1.25-1.99) at 3, 6, and 12 months, respectively.
      Adverse effects with combination nicotine replacement therapy were minimal and
      similar to placebo or monotherapy. CONCLUSION: Current literature indicates that
      combination therapy is statistically better than monotherapy in smoking cessation
      treatment as assessed by 3-, 6-, and 12-month abstinence rates. Adverse effects
      and adherence to combination therapy are similar to monotherapy and placebo.

PMID- 18826908
TI  - Edwin Leigh Newcomb 1882-1950: pharmacy's many-sided man.

PMID- 18826909
TI  - Influenza vaccination: outlook for 2008-09 season.

PMID- 18826910
TI  - New drugs: methylnaltrexone bromide, alvimopan, and rilonacept.

PMID- 18826912
TI  - Introduction. Biomolecular simulation.
AB  - 'Everything that living things do can be understood in terms of the jigglings and
      wigglings of atoms' as Richard Feynman provocatively stated nearly 50 years ago.
      But how can we 'see' this wiggling and jiggling and understand how it drives
      biology? Increasingly, computer simulations of biological macromolecules are
      helping to meet this challenge.

PMID- 18826913
TI  - Dynamics of conserved waters in human Hsp90: implications for drug design.
AB  - The flexibility of a promising protein target, human heat shock protein 90
      (Hsp90), is investigated by molecular dynamics simulations. These simulations
      focus on: (i) the interactions between the protein and conserved water molecules;
      and (ii) the interactions of the ligand PU3, the conserved water molecules and
      the protein. This is followed by a virtual screening docking study of the PU3
      family of compounds and Hsp90 incorporating several conserved water molecules.

PMID- 18826914
TI  - Structure and properties of strontium-doped phosphate-based glasses.
AB  - Owing to similarity in both ionic size and polarity, strontium (Sr2+) is known to
      behave in a comparable way to calcium (Ca2+), and its role in bone metabolism has
      been well documented as both anti-resorptive and bone forming. In this study,
      novel quaternary strontium-doped phosphate-based glasses, containing 1, 3 and 5
      mol% SrO, were synthesized and characterized. (31)P magic angle spinning (MAS)
      nuclear magnetic resonance results showed that, as the Sr2+ content is increased
      in the glasses, there is a slight increase in disproportionation of Q2 phosphorus
      environments into Q(1) and Q3 environments. Moreover, shortening and
      strengthening of the phosphorus to bridging oxygen distance occurred as obtained
      from FTIR. The general broadening of the spectral features with Sr2+ content is
      most probably due to the increased variation of the phosphate-cation bonding
      interactions caused by the introduction of the third cation. This increased
      disorder may be the cause of the increased degradation of the Sr-containing
      glasses relative to the Sr-free glass. As confirmed from elemental analysis, all
      Sr-containing glasses showed higher Na2O than expected and this also could be
      accounted for by the higher degradation of these glasses compared with Sr-free
      glasses. Measurements of surface free energy (SFE) showed that incorporation of
      strontium had no effect on SFE, and samples had relatively higher fractional
      polarity, which is not expected to promote high cell activity. From viability
      studies, however, the incorporation of Sr2+ showed better cellular response than
      Sr(2+)-free glasses, but still lower than the positive control. This unfavourable
      cellular response could be due to the high degradation nature of these glasses
      and not due to the presence of Sr2+.

PMID- 18826915
TI  - Origin and differentiation of the Earth: past to present. Preface.

PMID- 18826916
TI  - A young Moon-forming giant impact at 70-110 million years accompanied by late
      stage mixing, core formation and degassing of the Earth.
AB  - New W isotope data for lunar metals demonstrate that the Moon formed late in
      isotopic equilibrium with the bulk silicate Earth (BSE). On this basis, lunar Sr
      isotope data are used to define the former composition of the Earth and hence the
      Rb-Sr age of the Moon, which is 4.48+/-0.02Ga, or 70-110Ma (million years) after
      the start of the Solar System. This age is significantly later than had been
      deduced from W isotopes based on model assumptions or isotopic effects now known
      to be cosmogenic. The Sr age is in excellent agreement with earlier estimates
      based on the time of lunar Pb loss and the age of the early lunar crust (4.46+/
      0.04Ga). Similar ages for the BSE are recorded by xenon and lead-lead, providing
      evidence of catastrophic terrestrial degassing, atmospheric blow-off and
      significant late core formation accompanying the ca 100Ma giant impact. Agreement
      between the age of the Moon based on the Earth's Rb/Sr and the lead-lead age of
      the Moon is consistent with no major losses of moderately volatile elements from
      the Earth during the giant impact. The W isotopic composition of the BSE can be
      explained by end member models of (i) gradual accretion with a mean life of
      roughly 35Ma or (ii) rapid growth with a mean life of roughly 10Ma, followed by a
      significant hiatus prior to the giant impact. The former assumes that
      approximately 60 per cent of the incoming metal from impactors is added directly
      to the core during accretion. The latter includes complete mixing of all the
      impactor material into the BSE during accretion. The identical W isotopic
      composition of the Moon and the BSE limits the amount of material that can be
      added as a late veneer to the Earth after the giant impact to less than 0.3+/-0.3
      per cent of ordinary chondrite or less than 0.5+/-0.6 per cent CI carbonaceous
      chondrite based on their known W isotopic compositions. Neither of these on their
      own is sufficient to explain the inventories of both refractory siderophiles such
      as platinum group elements and rhenium, and volatiles such as sulphur, carbon and
      water.

PMID- 18826917
TI  - Boreal forests, aerosols and the impacts on clouds and climate.
AB  - Previous studies have concluded that boreal forests warm the climate because the
      cooling from storage of carbon in vegetation and soils is cancelled out by the
      warming due to the absorption of the Sun's heat by the dark forest canopy.
      However, these studies ignored the impacts of forests on atmospheric aerosol. We
      use a global atmospheric model to show that, through emission of organic vapours
      and the resulting condensational growth of newly formed particles, boreal forests
      double regional cloud condensation nuclei concentrations (from approx. 100 to
      approx. 200 cm(-3)). Using a simple radiative model, we estimate that the
      resulting change in cloud albedo causes a radiative forcing of between -1.8 and 
      6.7 W m(-2) of forest. This forcing may be sufficiently large to result in boreal
      forests having an overall cooling impact on climate. We propose that the
      combination of climate forcings related to boreal forests may result in an
      important global homeostasis. In cold climatic conditions, the snow-vegetation
      albedo effect dominates and boreal forests warm the climate, whereas in warmer
      climates they may emit sufficiently large amounts of organic vapour modifying
      cloud albedo and acting to cool climate.

PMID- 18826918
TI  - Experiments on metal-silicate plumes and core formation.
AB  - Short-lived isotope systematics, mantle siderophile abundances and the power
      requirements of the geodynamo favour an early and high-temperature core-formation
      process, in which metals concentrate and partially equilibrate with silicates in
      a deep magma ocean before descending to the core. We report results of laboratory
      experiments on liquid metal dynamics in a two-layer stratified viscous fluid,
      using sucrose solutions to represent the magma ocean and the crystalline, more
      primitive mantle and liquid gallium to represent the core-forming metals. Single
      gallium drop experiments and experiments on Rayleigh-Taylor instabilities with
      gallium layers and gallium mixtures produce metal diapirs that entrain the less
      viscous upper layer fluid and produce trailing plume conduits in the high
      viscosity lower layer. Calculations indicate that viscous dissipation in metal
      silicate plumes in the early Earth would result in a large initial core
      superheat. Our experiments suggest that metal-silicate mantle plumes facilitate
      high-pressure metal-silicate interaction and may later evolve into buoyant
      thermal plumes, connecting core formation to ancient hotspot activity on the
      Earth and possibly on other terrestrial planets.

PMID- 18826919
TI  - New geochemical insights into volcanic degassing.
AB  - Magma degassing plays a fundamental role in controlling the style of volcanic
      eruptions. Whether a volcanic eruption is explosive, or effusive, is of crucial
      importance to approximately 500 million people living in the shadow of hazardous
      volcanoes worldwide. Studies of how gases exsolve and separate from magma prior
      to and during eruptions have been given new impetus by the emergence of more
      accurate and automated methods to measure volatile species both as volcanic gases
      and dissolved in the glasses of erupted products. The composition of volcanic
      gases is dependent on a number of factors, the most important being magma
      composition and the depth of gas-melt segregation prior to eruption; this latter
      parameter has proved difficult to constrain in the past, yet is arguably the most
      critical for controlling eruptive style. Spectroscopic techniques operating in
      the infrared have proved to be of great value in measuring the composition of
      gases at high temporal resolution. Such methods, when used in tandem with
      microanalytical geochemical investigations of erupted products, are leading to
      better constraints on the depth at which gases are generated and separated from
      magma. A number of recent studies have focused on transitions between explosive
      and effusive activity and have led to a better understanding of gas-melt
      segregation at basaltic volcanoes. Other studies have focused on degassing during
      intermediate and silicic eruptions. Important new results include the recognition
      of fluxing by deep-derived gases, which buffer the amount of dissolved volatiles
      in the melt at shallow depths, and the observation of gas flow up permeable
      conduit wall shear zones, which may be the primary mechanism for gas loss at the
      cusp of the most explosive and unpredictable volcanic eruptions. In this paper, I
      review current and future directions in the field of geochemical studies of
      volcanic degassing processes and illustrate how the new insights are beginning to
      change the way in which we understand and classify volcanic eruptions.

PMID- 18826920
TI  - Isotopes as clues to the origin and earliest differentiation history of the
      Earth.
AB  - Measurable variations in (182)W/(183)W, (142)Nd/(144)Nd, (129)Xe/(130)Xe and
      (136)XePu/(130)Xe in the Earth and meteorites provide a record of accretion and
      formation of the core, early crust and atmosphere. These variations are due to
      the decay of the now extinct nuclides (182)Hf, (146)Sm, (129)I and (244)Pu. The
      (l82)Hf-(182)W system is the best accretion and core-formation chronometer, which
      yields a mean time of Earth's formation of 10Myr, and a total time scale of
      30Myr. New laser shock data at conditions comparable with those in the Earth's
      deep mantle subsequent to the giant Moon-forming impact suggest that metal
      silicate equilibration was rapid enough for the Hf-W chronometer to reliably
      record this time scale. The coupled (146)Sm-(147)Sm chronometer is the best
      system for determining the initial silicate differentiation (magma ocean
      crystallization and proto-crust formation), which took place at ca 4.47Ga or
      perhaps even earlier. The presence of a large (129)Xe excess in the deep Earth is
      consistent with a very early atmosphere formation (as early as 30Myr); however,
      the interpretation is complicated by the fact that most of the atmospheric Xe may
      be from a volatile-rich late veneer.

PMID- 18826921
TI  - Some recent advances in understanding the mineralogy of Earth's deep mantle.
AB  - Understanding planetary structure and evolution requires a detailed knowledge of
      the properties of geological materials under the conditions of deep planetary
      interiors. Experiments under the extreme pressure-temperature conditions of the
      deep mantle are challenging, and many fundamental properties remain poorly
      constrained or are inferred only through uncertain extrapolations from lower
      pressure-temperature states. Nevertheless, the last several years have witnessed
      a number of new developments in this area, and a broad overview of the current
      understanding of the Earth's lower mantle is presented here. Some recent
      experimental and theoretical advances related to the lowermost mantle are
      highlighted. Measurements of the equation of state and deformation behaviour of
      (Mg,Fe)SiO3 in the CaIrO3-type (post-perovskite) structure yield insights into
      the nature of the core-mantle boundary region. Theoretical studies of the
      behaviour of MgSiO3 liquids under high pressure-temperature conditions provide
      constraints on melt volumes, diffusivities and viscosities that are relevant to
      understanding both the early Earth (e.g. deep magma oceans) and seismic structure
      observed in the present Earth (e.g. ultra-low-velocity zones).

PMID- 18826922
TI  - Composition of the Earth's interior: the importance of early events.
AB  - The detection of excess 142Nd caused by the decay of 103Ma half-life 146Sm in all
      terrestrial rocks compared with chondrites shows that the chondrite analogue
      compositional model cannot be strictly correct, at least for the accessible
      portion of the Earth. Both the continental crust (CC) and the mantle source of
      mid-ocean ridge basalts (MORB) originate from the material characterized by
      superchondritic 142Nd/144Nd. Thus, the mass balance of CC plus mantle depleted by
      crust extraction (the MORB-source mantle) does not sum back to chondritic
      compositions, but instead to a composition with Sm/Nd ratio sufficiently high to
      explain the superchondritic 142Nd/144Nd. This requires that the mass of mantle
      depleted by CC extraction expand to 75-100 per cent of the mantle depending on
      the composition assumed for average CC. If the bulk silicate Earth has chondritic
      relative abundances of the refractory lithophile elements, then there must exist
      within the Earth's interior an incompatible-element-enriched reservoir that
      contains roughly 40 per cent of the Earth's 40Ar and heat-producing radioactive
      elements. The existence of this enriched reservoir is demonstrated by time
      varying 142Nd/144Nd in Archaean crustal rocks. Calculations of the mass of the
      enriched reservoir along with seismically determined properties of the D'' layer
      at the base of the mantle allow the speculation that this enriched reservoir
      formed by the sinking of dense melts deep in a terrestrial magma ocean. The
      enriched reservoir may now be confined to the base of the mantle owing to a
      combination of compositionally induced high density and low viscosity, both of
      which allow only minimal entrainment into the overlying convecting mantle.

PMID- 18826923
TI  - What CO2 well gases tell us about the origin of noble gases in the mantle and
      their relationship to the atmosphere.
AB  - Study of commercially produced volcanic CO2 gas associated with the Colorado
      Plateau, USA, has revealed substantial new information about the noble gas
      isotopic composition and elemental abundance pattern of the mantle. Combined with
      published data from mid-ocean ridge basalts, it is now clear that the convecting
      mantle has a maximum (20)Ne/(22)Ne isotopic composition, indistinguishable from
      that attributed to solar wind-implanted (SWI) neon in meteorites. This is
      distinct from the higher (20)Ne/(22)Ne isotopic value expected for solar nebula
      gases. The non-radiogenic xenon isotopic composition of the well gases shows that
      20 per cent of the mantle Xe is 'solar-like' in origin, but cannot resolve the
      small isotopic difference between the trapped meteorite 'Q'-component and solar
      Xe. The mantle primordial (20)Ne/(132)Xe is approximately 1400 and is comparable
      with the upper end of that observed in meteorites. Previous work using the
      terrestrial (129)I - (129)Xe mass balance demands that almost 99 per cent of the
      Xe (and therefore other noble gases) has been lost from the accreting solids and
      that Pu-I closure age models have shown this to have occurred in the first ca
      100Ma of the Earth's history. The highest concentrations of Q-Xe and solar wind
      implanted (SWI)-Ne measured in meteorites allow for this loss and these high
      abundance samples have a Ne/Xe ratio range compatible with the 'recycled-air
      corrected' terrestrial mantle. These observations do not support models in which
      the terrestrial mantle acquired its volatiles from the primary capture of solar
      nebula gases and, in turn, strongly suggest that the primary terrestrial
      atmosphere, before isotopic fractionation, is most probably derived from degassed
      trapped volatiles in accreting material.By contrast, the non-radiogenic argon,
      krypton and 80 per cent of the xenon in the convecting mantle have the same
      isotopic composition and elemental abundance pattern as that found in seawater
      with a small sedimentary Kr and Xe admix. These mantle heavy noble gases are
      dominated by recycling of air dissolved in seawater back into the mantle.
      Numerical simulations suggest that plumes sampling the core-mantle boundary would
      be enriched in seawater-derived noble gases compared with the convecting mantle,
      and therefore have substantially lower (40)Ar/(36)Ar. This is compatible with
      observation. The subduction process is not a complete barrier to volatile return
      to the mantle.

PMID- 18826924
TI  - The redox state of the mantle during and just after core formation.
AB  - Siderophile elements are depleted in the Earth's mantle, relative to chondritic
      meteorites, as a result of equilibration with core-forming Fe-rich metal.
      Measurements of metal-silicate partition coefficients show that mantle depletions
      of slightly siderophile elements (e.g. Cr, V) must have occurred at more reducing
      conditions than those inferred from the current mantle FeO content. This implies
      that the oxidation state (i.e. FeO content) of the mantle increased with time as
      accretion proceeded. The oxygen fugacity of the present-day upper mantle is
      several orders of magnitude higher than the level imposed by equilibrium with
      core-forming Fe metal. This results from an increase in the Fe2O3 content of the
      mantle that probably occurred in the first 1Ga of the Earth's history. Here we
      explore fractionation mechanisms that could have caused mantle FeO and Fe2O3
      contents to increase while the oxidation state of accreting material remained
      constant (homogeneous accretion). Using measured metal-silicate partition
      coefficients for O and Si, we have modelled core-mantle equilibration in a magma
      ocean that became progressively deeper as accretion proceeded. The model
      indicates that the mantle would have become gradually oxidized as a result of Si
      entering the core. However, the increase in mantle FeO content and oxygen
      fugacity is limited by the fact that O also partitions into the core at high
      temperatures, which lowers the FeO content of the mantle. (Mg,Fe)(Al,Si)O3
      perovskite, the dominant lower mantle mineral, has a strong affinity for Fe2O3
      even in the presence of metallic Fe. As the upper mantle would have been poor in
      Fe2O3 during core formation, FeO would have disproportionated to produce Fe2O3
      (in perovskite) and Fe metal. Loss of some disproportionated Fe metal to the core
      would have enriched the remaining mantle in Fe2O3 and, if the entire mantle was
      then homogenized, the oxygen fugacity of the upper mantle would have been raised
      to its present-day level.

PMID- 18826925
TI  - Early differentiation of the Earth and the Moon.
AB  - We examine the implications of new 182W and 142Nd data for Mars and the Moon for
      the early evolution of the Earth. The similarity of 182W in the terrestrial and
      lunar mantles and their apparently differing Hf/W ratios indicate that the Moon
      forming giant impact most probably took place more than 60Ma after the formation
      of calcium-aluminium-rich inclusions (4.568Gyr). This is not inconsistent with
      the apparent U-Pb age of the Earth. The new 142Nd data for Martian meteorites
      show that Mars probably has a super-chondritic Sm/Nd that could coincide with
      that of the Earth and the Moon. If this is interpreted by an early mantle
      differentiation event, this requires a buried enriched reservoir for the three
      objects. This is highly unlikely. For the Earth, we show, based on new mass
      balance calculations for Nd isotopes, that the presence of a hidden reservoir is
      difficult to reconcile with the combined 142Nd-143Nd systematics of the Earth's
      mantle. We argue that a likely possibility is that the missing component was lost
      during or prior to accretion. Furthermore, the 142Nd data for the Moon that were
      used to argue for the solidification of the magma ocean at ca 200Myr are
      reinterpreted. Cumulate overturn, magma mixing and melting following lunar magma
      ocean crystallization at 50-100Myr could have yielded the 200Myr model age.

PMID- 18826926
TI  - Accretion and core formation: constraints from metal-silicate partitioning.
AB  - Experimental metal-silicate partitioning data for Ni, Co, V, Cr, Nb, Mn, Si and W
      were used to investigate the geochemical consequences of a range of models for
      accretion and core formation on Earth. The starting assumptions were chondritic
      ratios of refractory elements in the Earth and the segregation of metal at the
      bottom of a magma ocean, which deepened as the planet grew and which had, at its
      base, a temperature close to the liquidus of the silicate. The models examined
      were as follows. (i) Continuous segregation from a mantle which is chemically
      homogeneous and which has a fixed oxidation state, corresponding to 6.26 per cent
      oxidized Fe. Although Ni, Co and W partitioning is consistent with chondritic
      ratios, the current V content of the silicate Earth cannot be reconciled with
      core segregation under these conditions of fixed oxidation state. (ii) Continuous
      segregation from a mantle which is chemically homogeneous but in which the Earth
      became more oxidized as it grew. In this case, the Ni, Co, W, V, Cr and Nb
      contents of core and mantle are easily matched to those calculated from the
      chondritic ratios of refractory elements. The magma ocean is calculated to
      maintain a thickness approximately 35 per cent of the depth to the core-mantle
      boundary in the accreting Earth, yielding a maximum pressure of 44GPa. This model
      yields a Si content of the core of 5.7 per cent, in good agreement with
      cosmochemical estimates and with recent isotopic data. (iii) Continuous
      segregation from a mantle which is not homogeneous and in which the core
      equilibrates with a restricted volume of mantle at the base of the magma ocean.
      This is found to increase depth of the magma ocean by approximately 50 per cent.
      All of the other elements (except Mn) have partitioning consistent with
      chondritic abundances in the Earth, provided the Earth became, as before,
      progressively oxidized during accretion. (iv) Continuous segregation of metal
      from a crystal-melt mush. In this case, pressures decrease to a maximum of 31GPa
      and it is extremely difficult to match the calculated mantle contents of the
      highly incompatible elements Nb and W to those observed. Progressive oxidation is
      required to fit the observed mantle contents of vanadium. All of the scenarios
      discussed above point to progressive oxidation having occurred as the Earth grew.
      The Earth appears to be depleted in Mn relative to the chondritic reference.

PMID- 18826927
TI  - Collisional erosion and the non-chondritic composition of the terrestrial
      planets.
AB  - The compositional variations among the chondrites inform us about cosmochemical
      fractionation processes during condensation and aggregation of solid matter from
      the solar nebula. These fractionations include: (i) variable Mg-Si-RLE ratios
      (RLE: refractory lithophile element), (ii) depletions in elements more volatile
      than Mg, (iii) a cosmochemical metal-silicate fractionation, and (iv) variations
      in oxidation state. Moon- to Mars-sized planetary bodies, formed by rapid
      accretion of chondrite-like planetesimals in local feeding zones within 106
      years, may exhibit some of these chemical variations. However, the next stage of
      planetary accretion is the growth of the terrestrial planets from approximately
      102 embryos sourced across wide heliocentric distances, involving energetic
      collisions, in which material may be lost from a growing planet as well as
      gained. While this may result in averaging out of the 'chondritic'
      fractionations, it introduces two non-chondritic chemical fractionation
      processes: post-nebular volatilization and preferential collisional erosion. In
      the latter, geochemically enriched crust formed previously is preferentially
      lost. That post-nebular volatilization was widespread is demonstrated by the non
      chondritic Mn/Na ratio in all the small, differentiated, rocky bodies for which
      we have basaltic samples, including the Moon and Mars. The bulk silicate Earth
      (BSE) has chondritic Mn/Na, but shows several other compositional features in its
      pattern of depletion of volatile elements suggestive of non-chondritic
      fractionation. The whole-Earth Fe/Mg ratio is 2.1+/-0.1, significantly greater
      than the solar ratio of 1.9+/-0.1, implying net collisional erosion of
      approximately 10 per cent silicate relative to metal during the Earth's
      accretion. If this collisional erosion preferentially removed differentiated
      crust, the assumption of chondritic ratios among all RLEs in the BSE would not be
      valid, with the BSE depleted in elements according to their geochemical
      incompatibility. In the extreme case, the Earth would only have half the
      chondritic abundances of the highly incompatible, heat-producing elements Th, U
      and K. Such an Earth model resolves several geochemical paradoxes: the depleted
      mantle occupies the whole mantle, is completely outgassed in (40)Ar and produces
      the observed (4)He flux through the ocean basins. But the lower radiogenic heat
      production exacerbates the discrepancy with heat loss.

PMID- 18826928
TI  - Accretion of the Earth.
AB  - The origin of the Earth and its Moon has been the focus of an enormous body of
      research. In this paper I review some of the current models of terrestrial planet
      accretion, and discuss assumptions common to most works that may require re
      examination. Density-wave interactions between growing planets and the gas nebula
      may help to explain the current near-circular orbits of the Earth and Venus, and
      may result in large-scale radial migration of proto-planetary embryos. Migration
      would weaken the link between the present locations of the planets and the
      original provenance of the material that formed them. Fragmentation can
      potentially lead to faster accretion and could also damp final planet orbital
      eccentricities. The Moon-forming impact is believed to be the final major event
      in the Earth's accretion. Successful simulations of lunar-forming impacts involve
      a differentiated impactor containing between 0.1 and 0.2 Earth masses, an impact
      angle near 45 degrees and an impact speed within 10 per cent of the Earth's
      escape velocity. All successful impacts-with or without pre-impact rotation-imply
      that the Moon formed primarily from material originating from the impactor rather
      than from the proto-Earth. This must ultimately be reconciled with compositional
      similarities between the Earth and the Moon.

PMID- 18826929
TI  - Compressibility of water in magma and the prediction of density crossovers in
      mantle differentiation.
AB  - Hydrous silicate melts appear to have greater compressibility relative to
      anhydrous melts of the same composition at low pressures (<2GPa); however, at
      higher pressures, this difference is greatly reduced and becomes very small at
      pressures above 5GPa. This implies that the pressure effect on the partial molar
      volume of water in silicate melt ( partial differentialV-H2O/ partial
      differentialP) is highly dependent on pressure regime. Thus, H2O can be thought
      of as the most compressible 'liquid oxide' component in silicate melt at low
      pressure, but at high pressure its compressibility resembles that of other liquid
      oxide components. A best-fit curve to the data on V-H2O from various studies
      allows calculation of hydrous melt compression curves relevant to high-pressure
      planetary differentiation. From these compression curves, crystal-liquid density
      crossovers are predicted for the mantles of the Earth and Mars. For the Earth,
      trapped dense hydrous melts may reside atop the 410km discontinuity, and,
      although not required to be hydrous, atop the core-mantle boundary (CMB), in
      accord with seismic observations of low-velocity zones in these regions. For
      Mars, a density crossover at the base of the upper mantle is predicted, which
      would produce a low-velocity zone at a depth of approximately 1200km. If
      perovskite is stable at the base of the Martian mantle, then density crossovers
      or trapped dense hydrous melts are unlikely to reside there, and long-lived, melt
      induced, low-velocity regions atop the CMB are not predicted.

PMID- 18826930
TI  - Assessing visual requirements for social context-dependent activation of the
      songbird song system.
AB  - Social context has been shown to have a profound influence on brain activation in
      a wide range of vertebrate species. Best studied in songbirds, when males sing
      undirected song, the level of neural activity and expression of immediate early
      genes (IEGs) in several song nuclei is dramatically higher or lower than when
      they sing directed song to other birds, particularly females. This differential
      social context-dependent activation is independent of auditory input and is not
      simply dependent on the motor act of singing. These findings suggested that the
      critical sensory modality driving social context-dependent differences in the
      brain could be visual cues. Here, we tested this hypothesis by examining IEG
      activation in song nuclei in hemispheres to which visual input was normal or
      blocked. We found that covering one eye blocked visually induced IEG expression
      throughout both contralateral visual pathways of the brain, and reduced
      activation of the contralateral ventral tegmental area, a non-visual midbrain
      motivation-related area affected by social context. However, blocking visual
      input had no effect on the social context-dependent activation of the
      contralateral song nuclei during female-directed singing. Our findings suggest
      that individual sensory modalities are not direct driving forces for the social
      context differences in song nuclei during singing. Rather, these social context
      differences in brain activation appear to depend more on the general sense that
      another individual is present.

PMID- 18826931
TI  - Genomic evidence for a large-Z effect.
AB  - The 'large-X effect' suggests that sex chromosomes play a disproportionate role
      in adaptive evolution. Theoretical work indicates that this effect may be most
      pronounced in genetic systems with female heterogamety under both good-genes and
      Fisher's runaway models of sexual selection (males ZZ, females ZW). Here, I use a
      comparative genomic approach (alignments of several thousands of chicken-zebra
      finch-human-mouse-opossum orthologues) to show that avian Z-linked genes are
      highly overrepresented among those bird-mammalian orthologues that show evidence
      of accelerated rate of functional evolution in birds relative to mammals; the
      data suggest a twofold excess of such genes on the Z chromosome. A reciprocal
      analysis of genes accelerated in mammals found no evidence for an excess of X
      linkage. This would be compatible with theoretical expectations for differential
      selection on sex-linked genes under male and female heterogamety, although the
      power in this case was not sufficient to statistically show that 'large-Z' was
      more pronounced than 'large-X'. Accelerated Z-linked genes include a variety of
      functional categories and are characterized by higher non-synonymous to
      synonymous substitution rate ratios than both accelerated autosomal and non
      accelerated genes. This points at a genomic 'large-Z effect', which is widespread
      and of general significance for adaptive divergence in birds.

PMID- 18826932
TI  - Human-mediated dispersal of seeds over long distances.
AB  - Human activities have fundamental impacts on the distribution of species through
      altered land use, but also directly by dispersal of propagules. Rare long
      distance dispersal events have a disproportionate importance for the spread of
      species including invasions. While it is widely accepted that humans may act as
      vectors of long-distance dispersal, there are few studies that quantify this
      process. We studied in detail a mechanism of human-mediated dispersal (HMD). For
      two plant species we measured, over a wide range of distances, how many seeds are
      carried by humans on shoes. While over half of the seeds fell off within 5m,
      seeds were regularly still attached to shoes after 5 km. Semi-mechanistic models
      were fitted, and these suggested that long-distance dispersal on shoes is
      facilitated by decreasing seed detachment probability with distance. Mechanistic
      modelling showed that the primary vector, wind, was less important as an agent of
      long-distance dispersal, dispersing seeds less than 250 m. Full dispersal kernels
      were derived by combining the models for primary dispersal by wind and secondary
      dispersal by humans. These suggest that walking humans can disperse seeds to very
      long distances, up to at least 10 km, and provide some of the first quantified
      dispersal kernels for HMD.

PMID- 18826933
TI  - Inferring malaria parasite population structure from serological networks.
AB  - The malaria parasite Plasmodium falciparum is characterized by high levels of
      genetic diversity at antigenic loci involved in virulence and immune evasion.
      Knowledge of the population structure and dynamics of these genes is important
      for designing control programmes and understanding the acquisition of immunity to
      malaria; however, high rates of homologous and non-homologous recombination as
      well as complex patterns of expression within hosts have hindered attempts to
      elucidate these structures experimentally. Here, we analyse serological data from
      Kenya using a novel network technique to deconstruct the relationships between
      patients' immune responses to different parasite isolates. We show that
      particular population structures and expression patterns produce distinctive
      signatures within serological networks of parasite recognition, which can be used
      to discriminate between competing hypotheses regarding the organization of these
      genes. Our analysis suggests that different levels of immune selection occur
      within different groups of the same multigene family leading to mixed population
      structures.

PMID- 18826934
TI  - The hierarchy of directional interactions in visual motion processing.
AB  - It is well known that context influences our perception of visual motion
      direction. For example, spatial and temporal context manipulations can be used to
      induce two well-known motion illusions: direction repulsion and the direction
      after-effect (DAE). Both result in inaccurate perception of direction when a
      moving pattern is either superimposed on (direction repulsion), or presented
      following adaptation to (DAE), another pattern moving in a different direction.
      Remarkable similarities in tuning characteristics suggest that common processes
      underlie the two illusions. What is not clear, however, is whether the processes
      driving the two illusions are expressions of the same or different neural
      substrates. Here we report two experiments demonstrating that direction repulsion
      and the DAE are, in fact, expressions of different neural substrates. Our
      strategy was to use each of the illusions to create a distorted perceptual
      representation upon which the mechanisms generating the other illusion could
      potentially operate. We found that the processes mediating direction repulsion
      did indeed access the distorted perceptual representation induced by the DAE.
      Conversely, the DAE was unaffected by direction repulsion. Thus parallels in
      perceptual phenomenology do not necessarily imply common neural substrates. Our
      results also demonstrate that the neural processes driving the DAE occur at an
      earlier stage of motion processing than those underlying direction repulsion.

PMID- 18826935
TI  - Between-group competition and human cooperation.
AB  - A distinctive feature of human behaviour is the widespread occurrence of
      cooperation among unrelated individuals. Explaining the maintenance of costly
      within-group cooperation is a challenge because the incentive to free ride on the
      efforts of other group members is expected to lead to decay of cooperation.
      However, the costs of cooperation can be diminished or overcome when there is
      competition at a higher level of organizational hierarchy. Here we show that
      competition between groups resolves the paradigmatic 'public goods' social
      dilemma and increases within-group cooperation and overall productivity. Further,
      group competition intensifies the moral emotions of anger and guilt associated
      with violations of the cooperative norm. The results suggest an important role
      for group conflict in the evolution of human cooperation and moral emotions.

PMID- 18826936
TI  - Testosterone and paternal care in East African foragers and pastoralists.
AB  - The 'challenge hypothesis' posits that testosterone facilitates reproductive
      effort (investment in male-male competition and mate-seeking) at the expense of
      parenting effort (investment in offspring and mates). Multiple studies, primarily
      in North America, have shown that men in committed relationships, fathers, or
      both maintain lower levels of testosterone than unpaired men. Data from non
      western populations, however, show inconsistent results. We hypothesized that
      much of this cross-cultural variation can be attributed to differential
      investment in mating versus parenting effort, even among married fathers. Here,
      we directly test this idea by comparing two neighbouring Tanzanian groups that
      exhibit divergent styles of paternal involvement: Hadza foragers and Datoga
      pastoralists. We predicted that high levels of paternal care by Hadza fathers
      would be associated with decreased testosterone in comparison with non-fathers,
      and that no such difference between fathers and non-fathers would be evident in
      Datoga men, who provide minimal direct paternal care. Twenty-seven Hadza men and
      80 Datoga men between the ages of 17 and 60 provided morning and afternoon saliva
      samples from which testosterone was assayed. Measurements in both populations
      confirmed these predictions, adding further support to the hypothesis that
      paternal care is associated with decreased testosterone production in men.

PMID- 18826937
TI  - The diverse origins of New Zealand house mice.
AB  - Molecular markers and morphological characters can help infer the colonization
      history of organisms. A combination of mitochondrial (mt) D-loop DNA sequences,
      nuclear DNA data, external measurements and skull characteristics shows that
      house mice (Mus musculus) in New Zealand and its outlying islands are descended
      from very diverse sources. The predominant genome is Mus musculus domesticus
      (from western Europe), but Mus musculus musculus (from central Europe) and Mus
      musculus castaneus (from southern Asia) are also represented genetically. These
      subspecies have hybridized to produce combinations of musculus and domesticus
      nuclear DNA coupled with domesticus mtDNA, and castaneus or musculus mtDNA with
      domesticus nuclear DNA. The majority of the mice with domesticus mtDNA that we
      sampled had D-loop sequences identical to two haplotypes common in Britain. This
      is consistent with long-term British-New Zealand cultural linkages. The origins
      of the castaneus mtDNA sequences widespread in New Zealand are less easy to
      identify.

PMID- 18826938
TI  - Bayesian coalescent inference of major human mitochondrial DNA haplogroup
      expansions in Africa.
AB  - Past population size can be estimated from modern genetic diversity using
      coalescent theory. Estimates of ancestral human population dynamics in sub
      Saharan Africa can tell us about the timing and nature of our first steps towards
      colonizing the globe. Here, we combine Bayesian coalescent inference with a
      dataset of 224 complete human mitochondrial DNA (mtDNA) sequences to estimate
      effective population size through time for each of the four major African mtDNA
      haplogroups (L0-L3). We find evidence of three distinct demographic histories
      underlying the four haplogroups. Haplogroups L0 and L1 both show slow, steady
      exponential growth from 156 to 213kyr ago. By contrast, haplogroups L2 and L3
      show evidence of substantial growth beginning 12-20 and 61-86kyr ago,
      respectively. These later expansions may be associated with contemporaneous
      environmental and/or cultural changes. The timing of the L3 expansion--8-12kyr
      prior to the emergence of the first non-African mtDNA lineages--together with
      high L3 diversity in eastern Africa, strongly supports the proposal that the
      human exodus from Africa and subsequent colonization of the globe was prefaced by
      a major expansion within Africa, perhaps driven by some form of cultural
      innovation.

PMID- 18826939
TI  - Of mice and (Viking?) men: phylogeography of British and Irish house mice.
AB  - The west European subspecies of house mouse (Mus musculus domesticus) has gained
      much of its current widespread distribution through commensalism with humans.
      This means that the phylogeography of M. m. domesticus should reflect patterns of
      human movements. We studied restriction fragment length polymorphism (RFLP) and
      DNA sequence variations in mouse mitochondrial (mt) DNA throughout the British
      Isles (328 mice from 105 localities, including previously published data). There
      is a major mtDNA lineage revealed by both RFLP and sequence analyses, which is
      restricted to the northern and western peripheries of the British Isles, and also
      occurs in Norway. This distribution of the 'Orkney' lineage fits well with the
      sphere of influence of the Norwegian Vikings and was probably generated through
      inadvertent transport by them. To form viable populations, house mice would have
      required large human settlements such as the Norwegian Vikings founded. The other
      parts of the British Isles (essentially most of mainland Britain) are
      characterized by house mice with different mtDNA sequences, some of which are
      also found in Germany, and which probably reflect both Iron Age movements of
      people and mice and earlier development of large human settlements. MtDNA studies
      on house mice have the potential to reveal novel aspects of human history.

PMID- 18826940
TI  - Subunits of mitochondrial complex I exist as part of matrix- and membrane
      associated subcomplexes in living cells.
AB  - Mitochondrial complex I (CI) is a large assembly of 45 different subunits, and
      defects in its biogenesis are the most frequent cause of mitochondrial disorders.
      In vitro evidence suggests a stepwise assembly process involving pre-assembled
      modules. However, whether these modules also exist in vivo is as yet unresolved.
      To answer this question, we here applied submitochondrial fluorescence recovery
      after photobleaching to HEK293 cells expressing 6 GFP-tagged subunits selected on
      the basis of current CI assembly models. We established that each subunit was
      partially present in a virtually immobile fraction, possibly representing the
      holo-enzyme. Four subunits (NDUFV1, NDUFV2, NDUFA2, and NDUFA12) were also
      present as highly mobile matrix-soluble monomers, whereas, in sharp contrast, the
      other two subunits (NDUFB6 and NDUFS3) were additionally present in a slowly
      mobile fraction. In the case of the integral membrane protein NDUFB6, this
      fraction most likely represented one or more membrane-bound subassemblies,
      whereas biochemical evidence suggested that for the NDUFS3 protein this fraction
      most probably corresponded to a matrix-soluble subassembly. Our results provide
      first time evidence for the existence of CI subassemblies in mitochondria of
      living cells.

PMID- 18826941
TI  - Activation of beta1,3-N-acetylglucosaminyltransferase-2 (beta3Gn-T2) by beta3Gn
      T8. Possible involvement of beta3Gn-T8 in increasing poly-N-acetyllactosamine
      chains in differentiated HL-60 cells.
AB  - Enzymatic activities of some glycosyltransferases are markedly increased via
      complex formation with other transferases or cofactor proteins. We previously
      showed that beta1,3-N-acetylglucosaminyltransferase-2 (beta3Gn-T2) and beta3Gn-T8
      can form a heterodimer in vitro and that the complex exhibits much higher
      enzymatic activity than either enzyme alone (Seko, A., and Yamashita, K. (2005)
      Glycobiology 15, 943-951). Here we examined this activation and the biological
      significance of complex formation in differentiated HL-60 cells. beta3Gn-T2 and 
      T8 were co-immunoprecipitated from the lysates of both-transfected COS-7 cells,
      indicating their association in vivo. We prepared inactive mutants of both
      enzymes by destroying the DXD motifs. The mixture of mutated beta3Gn-T2 and
      intact beta3Gn-T8 did not exhibit any activation, whereas the mixture of intact
      beta3Gn-T2 and mutated beta3Gn-T8 had increased activity, indicating the
      activation of beta3Gn-T2 via complex formation. Next, we compared expression
      levels of beta3Gn-T1-T8 in HL-60 cells and DMSO-treated differentiated HL-60
      cells, which produce larger poly-N-acetyllactosamine chains. The expression level
      of beta3Gn-T8 in the differentiated cells was 2.6-fold higher than in the
      untreated cells. Overexpression of beta3Gn-T8, but not beta3Gn-T2, induced an
      increase in poly-N-acetyllactosamine chains in HL-60 cells. These results raise a
      possibility that up-regulation of beta3Gn-T8 in differentiated HL-60 cells
      increases poly-N-acetyllactosamine chains by activating intrinsic beta3Gn-T2.

PMID- 18826942
TI  - H2O2-dependent hyperoxidation of peroxiredoxin 6 (Prdx6) plays a role in cellular
      toxicity via up-regulation of iPLA2 activity.
AB  - Peroxiredoxin 6 (Prdx6) is a bifunctional enzyme with peroxidase activity and
      Ca2+-independent phospholipase A2 (iPLA2) activity. Here, we report that H2O2
      induced cellular toxicity acts through Prdx6 hyperoxidation. Under high
      concentrations of H2O2 (> 100 microm), Prdx6, and 2-Cys Prdxs were hyperoxidized.
      Contrary to hyperoxidation of 2-Cys Prdxs, hyperoxidation of Prdx6 was
      irreversible in vivo. Surprisingly, H2O2-induced cell cycle arrest at the G2/M
      transition correlated with hyperoxidation and increased iPLA2 activity of Prdx6.
      This arrest was also associated with up-regulation of p53 and p21 and with down
      regulation of cyclin B1. Furthermore, the H2O2-mediated increase in iPLA2
      activity was dramatically abolished in a hyperoxidation mutant (C47A), an iPLA2
      mutant (S32A), and a double mutant (C47A/S32A) of Prdx6, demonstrating the
      essential requirement of Prdx6 C47 hyperoxidation for its iPLA2 activity.
      Together, our results demonstrate that H2O2-mediated hyperoxidation of Prdx6
      induces cell cycle arrest at the G2/M transition through up-regulation of iPLA2
      activity.

PMID- 18826943
TI  - Human carbonyl reductase 1 is an S-nitrosoglutathione reductase.
AB  - Human carbonyl reductase 1 (hCBR1) is an NADPH-dependent short chain
      dehydrogenase/reductase with broad substrate specificity and is thought to be
      responsible for the in vivo reduction of quinones, prostaglandins, and other
      carbonyl-containing compounds including xenobiotics. In addition, hCBR1 possesses
      a glutathione binding site that allows for increased affinity toward GSH
      conjugated molecules. It has been suggested that the GSH-binding site is near the
      active site; however, no structures with GSH or GSH conjugates have been
      reported. We have solved the x-ray crystal structures of hCBR1 and a substrate
      mimic in complex with GSH and the catalytically inert GSH conjugate
      hydroxymethylglutathione (HMGSH). The structures reveal the GSH-binding site and
      provide insight into the affinity determinants for GSH-conjugated substrates. We
      further demonstrate that the structural isostere of HMGSH, S-nitrosoglutathione,
      is an ideal hCBR1 substrate (Km = 30 microm, kcat = 450 min(-1)) with kinetic
      constants comparable with the best known hCBR1 substrates. Furthermore, we
      demonstrate that hCBR1 dependent GSNO reduction occurs in A549 lung
      adenocarcinoma cell lysates and suggest that hCBR1 may be involved in regulation
      of tissue levels of GSNO.

PMID- 18826944
TI  - Di-methyl H4 lysine 20 targets the checkpoint protein Crb2 to sites of DNA
      damage.
AB  - Histone lysine methylation is an important chromatin modification that can be
      catalyzed to a mono-, di-, or tri-methyl state. An ongoing challenge is to
      decipher how these different methyllysine histone marks can mediate distinct
      aspects of chromatin function. The fission yeast checkpoint protein Crb2 is
      rapidly targeted to sites of DNA damage after genomic insult, and this
      recruitment requires methylation of histone H4 lysine 20 (H4K20). Here we show
      that the tandem tudor domains of Crb2 preferentially bind the di-methylated H4K20
      residue. Loss of this interaction by disrupting either the tudor-binding motif or
      the H4K20 methylating enzyme Set9/Kmt5 ablates Crb2 localization to double-strand
      breaks and impairs checkpoint function. Further we show that dimethylation, but
      not tri-methylation, of H4K20 is required for Crb2 localization, checkpoint
      function, and cell survival after DNA damage. These results argue that the di
      methyl H4K20 modification serves as a binding target that directs Crb2 to sites
      of genomic lesions and defines an important genome integrity pathway mediated by
      a specific methyl-lysine histone mark.

PMID- 18826945
TI  - Mouse meningiocytes express Sox2 and yield high efficiency of chimeras after
      nuclear reprogramming with exogenous factors.
AB  - Induced pluripotent stem cell technology, also termed iPS, is an emerging
      approach to reprogram cells into an embryonic stem cell-like state by viral
      transduction with defined combinations of factors. iPS cells share most
      characteristics of embryonic stem cells, counting pluripotency and self-renewal,
      and have so far been obtained from mouse and humans, including patients with
      genetic diseases. Remarkably, autologous transplantation of cell lineages derived
      from iPS cells will eliminate the possibility of immunological rejection, as well
      as current ethical issues surrounding human embryonic stem cell research.
      However, before iPS can be used for clinical purposes, technical problems must be
      overcome. Among other considerations, full and homogeneous iPS reprogramming is
      an important prerequisite. However, despite the fact that cells from several
      mouse tissues can be successfully induced to iPS, the overall efficiency of
      chimera formation of these clones remains low even if selection for Oct4 or Nanog
      expression is applied. In this report, we demonstrate that cells from the mouse
      meningeal membranes express elevated levels of the embryonic master regulator
      Sox2 and are highly amenable to iPS. Meningeal iPS clones, generated without
      selection, are fully and homogeneously reprogrammed based on DNA methylation
      analysis and 100% chimera competent. Our results define a population of somatic
      cells that are ready to undergo iPS, thus highlighting a very attractive cell
      type for iPS research and application.

PMID- 18826946
TI  - Identification of an autoinhibitory mechanism that restricts C1 domain-mediated
      activation of the Rac-GAP alpha2-chimaerin.
AB  - Chimaerins are a family of GTPase activating proteins (GAPs) for the small G
      protein Rac that have gained recent attention due to their important roles in
      development, cancer, neuritogenesis, and T-cell function. Like protein kinase C
      isozymes, chimaerins possess a C1 domain capable of binding phorbol esters and
      the lipid second messenger diacylglycerol (DAG) in vitro. Here we identified an
      autoinhibitory mechanism in alpha2-chimaerin that restricts access of phorbol
      esters and DAG, thereby limiting its activation. Although phorbol 12-myristate 13
      acetate (PMA) caused limited translocation of wild-type alpha2-chimaerin to the
      plasma membrane, deletion of either N- or C-terminal regions greatly sensitize
      alpha2-chimaerin for intracellular redistribution and activation. Based on
      modeling analysis that revealed an occlusion of the ligand binding site in the
      alpha2-chimaerin C1 domain, we identified key amino acids that stabilize the
      inactive conformation. Mutation of these sites renders alpha2-chimaerin
      hypersensitive to C1 ligands, as reflected by its enhanced ability to translocate
      in response to PMA and to inhibit Rac activity and cell migration. Notably, in
      contrast to PMA, epidermal growth factor promotes full translocation of alpha2
      chimaerin in a phospholipase C-dependent manner, but not of a C1 domain mutant
      with reduced affinity for DAG (P216A-alpha2-chimaerin). Therefore, DAG generation
      and binding to the C1 domain are required but not sufficient for epidermal growth
      factor-induced alpha2-chimaerin membrane association. Our studies suggest a role
      for DAG in anchoring rather than activation of alpha2-chimaerin. Like other
      DAG/phorbol ester receptors, including protein kinase C isozymes, alpha2
      chimaerin is subject to autoinhibition by intramolecular contacts, suggesting a
      highly regulated mechanism for the activation of this Rac-GAP.

PMID- 18826947
TI  - The biflavonoid isoginkgetin is a general inhibitor of Pre-mRNA splicing.
AB  - Membrane-permeable compounds that reversibly inhibit a particular step in gene
      expression are highly useful tools for cell biological and biochemical/structural
      studies. In comparison with other gene expression steps where multiple small
      molecule effectors are available, very few compounds have been described that act
      as general inhibitors of pre-mRNA splicing. Here we report construction and
      validation of a set of mammalian cell lines suitable for the identification of
      small molecule inhibitors of pre-mRNA splicing. Using these cell lines, we
      identified the natural product isoginkgetin as a general inhibitor of both the
      major and minor spliceosomes. Isoginkgetin inhibits splicing both in vivo and in
      vitro at similar micromolar concentrations. It appears to do so by preventing
      stable recruitment of the U4/U5/U6 tri-small nuclear ribonucleoprotein, resulting
      in accumulation of the prespliceosomal A complex. Like two other recently
      reported general pre-mRNA splicing inhibitors, isoginkgetin has been previously
      described as an anti-tumor agent. Our results suggest that splicing inhibition is
      the mechanistic basis of the anti-tumor activity of isoginkgetin. Thus, pre-mRNA
      splicing inhibitors may represent a novel avenue for development of new anti
      cancer agents.

PMID- 18826948
TI  - The transcriptional coactivators SAGA, SWI/SNF, and mediator make distinct
      contributions to activation of glucose-repressed genes.
AB  - The paradigm of activation via ordered recruitment has evolved into a complicated
      picture as the influence of coactivators and chromatin structures on gene
      regulation becomes understood. We present here a comprehensive study of many
      elements of activation of ADH2 and FBP1, two glucose-regulated genes. We identify
      SWI/SNF as the major chromatin-remodeling complex at these genes, whereas SAGA
      (Spt-Ada-Gcn5-acetyltransferase complex) is required for stable recruitment of
      other coactivators. Mediator plays a crucial role in expression of both genes but
      does not affect chromatin remodeling. We found that Adr1 bound unaided by
      coactivators to ADH2, but Cat8 binding depended on coactivators at FBP1. Taken
      together, our results suggest that commonly regulated genes share many aspects of
      activation, but that gene-specific regulators or elements of promoter
      architecture may account for small differences in the mechanism of activation.
      Finally, we found that activator overexpression can compensate for the loss of
      SWI/SNF but not for the loss of SAGA.

PMID- 18826949
TI  - Internal core protein cleavage leaves the hepatitis B virus capsid intact and
      enhances its capacity for surface display of heterologous whole chain proteins.
AB  - Virus capsids find increasing use as nanoparticulate platforms for the surface
      display of heterologous ligands, including as multivalent vaccine carriers.
      Presentation on the icosahedral hepatitis B virus capsid (HBcAg) is known to
      strongly enhance immunogenicity of foreign sequences, most efficiently if they
      are inserted into the dominant c/e1 B cell epitope, a surface-exposed loop in the
      center of the constituent core protein primary sequence. Even some complete
      proteins were successfully inserted but others, e.g. the outer surface protein A
      (OspA) of the Lyme disease agent Borrelia burgdorferi, impaired formation of
      capsid-like particles (CLPs). This difference can be rationalized by the
      requirement for the termini of the insert to fit into the predetermined geometry
      of the two acceptor sites in the carrier. We reasoned that cleavage of one of the
      two bonds connecting insert and carrier should relieve these constraints,
      provided the cleaved protein fragments remain competent to support the particle
      structure. Indeed, HBcAg CLPs containing a recognition site for tobacco etch
      virus (TEV) protease in the c/e1 loop remained intact after cleavage, as did CLPs
      carrying a 65-residue peptide insertion. Most importantly, in situ cleavage of a
      core-OspA fusion protein by coexpressed TEV protease strongly enhanced CLP
      formation compared with the uncleaved protein. These data attest to the high
      structural stability of the HBcAg CLP and they significantly widen its
      applicability as a carrier for heterologous proteins. This approach should be
      adaptable to any protein-based particle with surface-exposed yet sequence
      internal loops.

PMID- 18826950
TI  - Constitutive activation of phosphatidylinositol 3-kinase signaling pathway down
      regulates TLR4-mediated tumor necrosis factor-alpha release in alveolar
      macrophages from asymptomatic HIV-positive persons in vitro.
AB  - Alveolar macrophages represent critical effector cells of innate immunity to
      infectious challenge in the lungs and recognize bacterial pathogens through
      pattern recognition receptors such as Toll-like receptors (TLRs).
      Phosphatidylinositol 3-kinase (PI3K) regulates TLR-mediated cytokine release, but
      whether HIV infection influences PI3K signaling pathway and alters TLR4-mediated
      macrophage response has not been investigated. In the current study, surface TLR4
      expression were similar but TLR4 activation (lipid A, 10 microg/ml) resulted in
      lower TNF-alpha release by HIV+ human macrophages compared with healthy cells.
      Pharmacological inhibition of PI3K (LY294002) normalized TNF-alpha release in
      HIV+ macrophages and augments ERK1/2 mitogen-activated protein kinase
      phosphorylation in response to lipid A. Importantly, HIV+ macrophages
      demonstrated increased constitutive phosphatidylinositol 3,4,5-trisphosphate
      formation, increased phosphorylation of downstream signaling molecules Akt and
      glycogen synthase kinase-3beta (GSK-3beta) at Ser9, and reduced PTEN protein
      expression. As a functional assessment of GSK-3beta phosphorylation, TLR4
      mediated interleukin-10 release was significantly higher in HIV+ human
      macrophages compared with healthy cells. Incubation of human macrophages with
      exogenous HIV Nef protein induced phosphorylation of Akt and GSK-3beta (whereas
      phosphorylation was reduced by PI3K inhibition) and promoted interleukin-10
      release. Taken together, these data demonstrate increased constitutive activation
      of the PI3K signaling pathway in HIV+ macrophages and support the concept that
      PI3K activation (by HIV proteins such as Nef) may contribute to reduced TLR4
      mediated TNF-alpha release in HIV+ human macrophages and impair host cell
      response to infectious challenge.

PMID- 18826951
TI  - Nanoscale increases in CD2-CD48-mediated intermembrane spacing decrease adhesion
      and reorganize the immunological synapse.
AB  - The relationship between intermembrane spacing, adhesion efficiency, and lateral
      organization of adhesion receptors has not been established for any adhesion
      system. We have utilized the CD2 ligand CD48 with two (wild type CD48 (CD48-WT)),
      four (CD48-CD2), or five (CD48-CD22) Ig-like domains. CD48-WT was 10-fold more
      efficient in mediating adhesion than CD48-CD2 or CD48-CD22. Electron tomography
      of contact areas with planar bilayers demonstrated average intermembrane spacing
      of 12.8 nm with CD48-WT, 14.7 nm with CD48-CD2, and 15.6 nm with CD48-CD22. Both
      CD48-CD2 and CD48-CD22 chimeras segregated completely from CD48-WT in mixed
      contact areas. In contrast, CD48-CD2 and CD48-CD22 co-localized when mixed
      contacts were formed. Confocal imaging of immunological synapses formed between
      primary T lymphocytes and Chinese hamster ovary cells presenting major
      histocompatibility complex-peptide complexes, and different forms of CD48
      demonstrated that CD48-CD2 and CD48-CD22 induce an eccentric CD2/T cell antigen
      receptor cluster. We propose that this reorganization of the immunological
      synapse sequesters the T cell antigen receptor in a location where it cannot
      interact with its ligand and dramatically reduces T cell sensitivity.

PMID- 18826952
TI  - Nrf1 and Nrf2 play distinct roles in activation of antioxidant response element
      dependent genes.
AB  - Nrf1 is a member of the vertebrate Cap'n'Collar (CNC) transcription factor family
      that commonly contains a unique basic-leucine zipper domain. Among CNC family
      members, Nrf2 is known to regulate a battery of antioxidant and xenobiotic
      metabolizing enzyme genes through the antioxidant response element (ARE).
      Although Nrf1 has also been shown to bind the ARE, it is unclear whether it plays
      a distinct role from Nrf2 in regulating genes with this element. To address this
      issue in vivo, we generated mice bearing a hepatocyte-specific disruption of the
      Nrf1 gene. AlthoughNrf2 knock-out mice did not exhibit liver damage when they
      were maintained in an unstressed condition, hepatocyte-specific deletion of Nrf1
      caused liver damage resembling the human disease non-alcoholic steatohepatitis.
      Gene expression analysis revealed that the disruption of Nrf1 causes stress that
      activates a number of ARE-driven genes in an Nrf2-dependent manner, indicating
      that Nrf2 cannot compensate completely for loss of Nrf1 function in the liver. In
      contrast, expression of metallothionein-1 and -2 (MT1 and MT2) genes, each of
      which harbors at least one ARE in its regulatory region, was decreased in the
      Nrf1-null mutant mice. Whereas Nrf1 and Nrf2 bound the MT1 ARE with comparable
      affinity, Nrf1 preferentially activated the reporter gene expression through the
      MT1 ARE. This study has, thus, identified the first ARE-dependent gene that
      relies exclusively on Nrf1, suggesting that it plays a distinct functional role
      in regulating ARE-driven genes.

PMID- 18826953
TI  - Identifying key components of the PrPC-PrPSc replicative interface.
AB  - In prion disease, direct interaction between the cellular prion protein (PrP(C))
      and its misfolded disease-associated conformer PrP(Sc) is a crucial, although
      poorly understood step promoting the formation of nascent PrP(Sc) and prion
      infectivity. Recently, we hypothesized that three regions of PrP (corresponding
      to amino acid residues 23-33, 98-110, and 136-158) interacting specifically and
      robustly with PrP(Sc), likely represent peptidic components of one flank of the
      prion replicative interface. In this study, we created epitope-tagged mouse
      PrP(C) molecules in which the PrP sequences 23-33, 98-110, and 136-158 were
      modified. These novel PrP molecules were individually expressed in the prion
      infected neuroblastoma cell line (ScN2a) and the conversion of each mutated mouse
      PrP(C) substrate to PrP(Sc) compared with that of the epitope-tagged wild-type
      mouse PrP(C). Mutations within PrP 98-110, substituting all 4 wild-type lysine
      residues with alanine residues, prevented conversion to PrP(Sc). Furthermore,
      when residues within PrP 136-140 were collectively scrambled, changed to
      alanines, or amino acids at positions 136, 137, and 139 individually replaced by
      alanine, conversion to PrP(Sc) was similarly halted. However, other PrP molecules
      containing mutations within regions 23-33 and 101-104 were able to readily
      convert to PrP(Sc). These results suggest that PrP sequence comprising residues
      98-110 and 136-140 not only participates in the specific binding interaction
      between PrP(C) and PrP(Sc), but also in the process leading to conversion of
      PrP(Sc)-sequestered PrP(C) into its disease-associated form.

PMID- 18826954
TI  - SCCRO (DCUN1D1) is an essential component of the E3 complex for neddylation.
AB  - Covalent modification of cullins by the ubiquitin-like protein NEDD8
      (neddylation) regulates protein ubiquitination by promoting the assembly of
      cullin-RING ligase E3 complexes. Like ubiquitination, neddylation results from an
      enzymatic cascade involving the sequential activity of a dedicated E1
      (APPBP1/Uba3), E2 (Ubc12), and an ill-defined E3. We show that SCCRO (also known
      as DCUN1D1) binds to the components of the neddylation pathway (Cullin-ROC1,
      Ubc12, and CAND1) and augments but is not required for cullin neddylation in
      reactions using purified recombinant proteins. We also show that SCCRO recruits
      Ubc12 approximately NEDD8 to the CAND1-Cul1-ROC1 complex but that this is not
      sufficient to dissociate or overcome the inhibitory effects of CAND1 on cullin
      neddylation in purified protein assays. In contrast to findings in cellular
      systems where no binding is seen, we show that SCCRO and CAND1 can bind to the
      neddylated Cul1-ROC1 complex in assays using purified recombinant proteins.
      Although neddylated (not unneddylated) Cul1-ROC1 is released from CAND1 upon
      incubation with testis lysate from SCCRO+/+ mice, the addition of recombinant
      SCCRO is required to achieve the same results in lysate from SCCRO(-/-) mice.
      Combined, these results suggest that SCCRO is an important component of the
      neddylation E3 complex that functions to recruit charged E2 and is involved in
      the release of inhibitory effects of CAND1 on cullin-RING ligase E3 complex
      assembly and activity.

PMID- 18826955
TI  - An activin/furin regulatory loop modulates the processing and secretion of
      inhibin alpha- and betaB-subunit dimers in pituitary gonadotrope cells.
AB  - Of all ligands of the transforming growth factor beta superfamily, inhibins and
      activins are a physiologically relevant pair that are functional antagonists of
      each other. Activin stimulates whereas inhibin blocks follicle-stimulating
      hormone biosynthesis and secretion from pituitary gonadotrope cells, and
      together, inhibin and activin control the pituitary gonadal axis essential for
      normal reproductive function. Sharing a similar beta-subunit, the secretion of
      inhibin heterodimers (alpha/beta) or activin homodimers (beta/beta) as mature
      bioactive ligands depends, in part, on the proteolytic processing of precursor
      proteins. A short loop regulatory pathway controlling precursor processing and
      dimer secretion was discovered. Activin stimulates endogenous inhibin alpha- and
      betaB-subunit mRNA, protein, and proteolytic processing. Simultaneously, activin
      stimulated the proconvertase furin through a Smad2/3-dependent process. The data
      provide a mechanism where the regulation of furin and inhibin subunits cooperates
      in an important positive short feedback loop. This regulatory loop augments the
      secretion of bioactive mature activin B, as well as inhibin B dimers, necessary
      for local follicle-stimulating hormone beta regulation.

PMID- 18826956
TI  - IP3 receptor binds to and sensitizes TRPV4 channel to osmotic stimuli via a
      calmodulin-binding site.
AB  - Activation of the non-selective cation channel TRPV4 by mechanical and osmotic
      stimuli requires the involvement of phospholipase A2 and the subsequent
      production of the arachidonic acid metabolites, epoxieicosatrienoic acids (EET).
      Previous studies have shown that inositol trisphosphate (IP3) sensitizes TRPV4 to
      mechanical, osmotic, and direct EET stimulation. We now search for the IP3
      receptor-binding site on TRPV4 and its relevance to IP3-mediated sensitization.
      Three putative sites involved in protein-protein interactions were evaluated: a
      proline-rich domain (PRD), a calmodulin (CaM)-binding site, and the last four
      amino acids (DAPL) that show a PDZ-binding motif-like. TRPV4-DeltaCaM-(Delta812
      831) channels preserved activation by hypotonicity, 4alpha-phorbol 12,13
      didecanoate, and EET but lost their physical interaction with IP3 receptor 3 and
      IP3-mediated sensitization. Deletion of a PDZ-binding motif-like (TRPV4
      DeltaDAPL) did not affect channel activity or IP3-mediated sensitization, whereas
      TRPV4-DeltaPRD-(Delta132-144) resulted in loss of channel function despite
      correct trafficking. We conclude that IP3-mediated sensitization requires IP3
      receptor binding to a TRPV4 C-terminal domain that overlaps with a previously
      described calmodulin-binding site.

PMID- 18826957
TI  - BNFinder: exact and efficient method for learning Bayesian networks.
AB  - MOTIVATION: Bayesian methods are widely used in many different areas of research.
      Recently, it has become a very popular tool for biological network
      reconstruction, due to its ability to handle noisy data. Even though there are
      many software packages allowing for Bayesian network reconstruction, only few of
      them are freely available to researchers. Moreover, they usually require at least
      basic programming abilities, which restricts their potential user base. Our goal
      was to provide software which would be freely available, efficient and usable to
      non-programmers. RESULTS: We present a BNFinder software, which allows for
      Bayesian network reconstruction from experimental data. It supports dynamic
      Bayesian networks and, if the variables are partially ordered, also static
      Bayesian networks. The main advantage of BNFinder is the use exact algorithm,
      which is at the same time very efficient (polynomial with respect to the number
      of observations).

PMID- 18826958
TI  - MSX-3D: a tool to validate 3D protein models using mass spectrometry.
AB  - MOTIVATION: The technique of chemical cross-linking followed by mass spectrometry
      has proven to bring valuable information about the protein structure and
      interactions between proteic subunits. It is an effective and efficient way to
      experimentally investigate some aspects of a protein structure when NMR and X-ray
      crystallography data are lacking. RESULTS: We introduce MSX-3D, a tool
      specifically geared to validate protein models using mass spectrometry. In
      addition to classical peptides identifications, it allows an interactive 3D
      visualization of the distance constraints derived from a cross-linking
      experiment. AVAILABILITY: Freely available at http://proteomics-pbil.ibcp.fr

PMID- 18826959
TI  - Smarter clustering methods for SNP genotype calling.
AB  - MOTIVATION: Most genotyping technologies for single nucleotide polymorphism (SNP)
      markers use standard clustering methods to 'call' the SNP genotypes. These
      methods are not always optimal in distinguishing the genotype clusters of a SNP
      because they do not take advantage of specific features of the genotype calling
      problem. In particular, when family data are available, pedigree information is
      ignored. Furthermore, prior information about the distribution of the
      measurements for each cluster can be used to choose an appropriate model-based
      clustering method and can significantly improve the genotype calls. One special
      genotyping problem that has never been discussed in the literature is that of
      genotyping of trisomic individuals, such as individuals with Down syndrome.
      Calling trisomic genotypes is a more complicated problem, and the addition of
      external information becomes very important. RESULTS: In this article, we discuss
      the impact of incorporating external information into clustering algorithms to
      call the genotypes for both disomic and trisomic data. We also propose two new
      methods to call genotypes using family data. One is a modification of the K-means
      method and uses the pedigree information by updating all members of a family
      together. The other is a likelihood-based method that combines the Gaussian or
      beta-mixture model with pedigree information. We compare the performance of these
      two methods and some other existing methods using simulation studies. We also
      compare the performance of these methods on a real dataset generated by the
      Illumina platform (www.illumina.com). AVAILABILITY: The R code for the family
      based genotype calling methods (SNPCaller) is available to be downloaded from the
      following website: http://watson.hgen.pitt.edu/register.

PMID- 18826960
TI  - The conserved translocase Tim17 prevents mitochondrial DNA loss.
AB  - Maintenance of an intact mitochondrial genome is essential for oxidative
      phosphorylation in all eukaryotes. Depletion of mitochondrial genome copy number
      can have severe pathological consequences due to loss of respiratory capacity. In
      Saccharomyces cerevisiae, several bifunctional metabolic enzymes have been shown
      to be required for mitochondrial DNA (mtDNA) maintenance. For example, Ilv5 is
      required for branched chain amino acid biosynthesis and mtDNA stability. We have
      identified OXA1 and TIM17 as novel multicopy suppressors of mtDNA instability in
      ilv5 cells. In addition, overexpression of TIM17, but not OXA1, prevents the
      complete loss of mtDNA in cells lacking the TFAM homologue Abf2. Introduction of
      the disease-associated A3243G mutant mtDNA into human NT2 teratocarcinoma cells
      frequently causes mtDNA loss. Yet when human TIM17A is overexpressed in NT2
      cybrids carrying A3243G mtDNA, the proportion of cybrid clones maintaining mtDNA
      increases significantly. TIM17A overexpression results in long-term mtDNA
      stabilization, since NT2 cybrids overexpressing TIM17A maintain mtDNA at levels
      similar to controls for several months. Tim17 is a conserved suppressor of mtDNA
      instability and is the first factor to be identified that can prevent mtDNA loss
      in a human cellular model of mitochondrial disease.

PMID- 18826961
TI  - Usher syndrome and Leber congenital amaurosis are molecularly linked via a novel
      isoform of the centrosomal ninein-like protein.
AB  - Usher syndrome (USH) and Leber congenital amaurosis (LCA) are autosomal recessive
      disorders resulting in syndromic and non-syndromic forms of blindness. In order
      to gain insight into the pathogenic mechanisms underlying retinal degeneration,
      we searched for interacting proteins of USH2A isoform B (USH2A(isoB)) and the
      LCA5-encoded protein lebercilin. We identified a novel isoform of the centrosomal
      ninein-like protein, hereby named Nlp isoform B (Nlp(isoB)), as a common
      interactor. Although we identified the capacity of this protein to bind calcium
      with one of its three EF-hand domains, the interacton with USH2A(isoB) did not
      depend on this. Upon expression in ARPE-19 cells, recombinant Nlp(isoB),
      lebercilin and USH2A(isoB) were all found to co-localize at the centrosomes.
      Staining of retinal sections with specific antibodies against all three proteins
      revealed their co-localization at the basal bodies of the photoreceptor
      connecting cilia. Based on this subcellular localization and the nature of their
      previously identified binding partners, we hypothesize that the pathogenic
      mechanisms for LCA and USH show significant overlap and involve defects in
      ciliogenesis, cilia maintenance and intraflagellar and/or microtubule-based
      transport. The direct association of Nlp(isoB) with USH2A(isoB) and lebercilin
      indicates that Nlp can be considered as a novel candidate gene for USH, LCA and
      allied retinal ciliopathies.

PMID- 18826962
TI  - Functional alterations of the ubiquitin-proteasome system in motor neurons of a
      mouse model of familial amyotrophic lateral sclerosis.
AB  - In familial and sporadic amyotrophic lateral sclerosis (ALS) and in rodent models
      of the disease, alterations in the ubiquitin-proteasome system (UPS) may be
      responsible for the accumulation of potentially harmful ubiquitinated proteins,
      leading to motor neuron death. In the spinal cord of transgenic mice expressing
      the familial ALS superoxide dismutase 1 (SOD1) gene mutation G93A (SOD1G93A), we
      found a decrease in constitutive proteasome subunits during disease progression,
      as assessed by real-time PCR and immunohistochemistry. In parallel, an increased
      immunoproteasome expression was observed, which correlated with a local
      inflammatory response due to glial activation. These findings support the
      existence of proteasome modifications in ALS vulnerable tissues. To functionally
      investigate the UPS in ALS motor neurons in vivo, we crossed SOD1G93A mice with
      transgenic mice that express a fluorescently tagged reporter substrate of the
      UPS. In double-transgenic Ub(G76V)-GFP /SOD1G93A mice an increase in Ub(G76V)-GFP
      reporter, indicative of UPS impairment, was detectable in a few spinal motor
      neurons and not in reactive astrocytes or microglia, at symptomatic stage but not
      before symptoms onset. The levels of reporter transcript were unaltered,
      suggesting that the accumulation of Ub(G76V)-GFP was due to deficient reporter
      degradation. In some motor neurons the increase of Ub(G76V)-GFP was accompanied
      by the accumulation of ubiquitin and phosphorylated neurofilaments, both markers
      of ALS pathology. These data suggest that UPS impairment occurs in motor neurons
      of mutant SOD1-linked ALS mice and may play a role in the disease progression.

PMID- 18826964
TI  - Remodelling of cardiac repolarization: how homeostatic responses can lead to
      arrhythmogenesis.
AB  - Cardiac action potentials (APs) are driven by ionic currents flowing through
      specific channels and exchangers across cardiomyocyte membranes. Once initiated
      by rapid Na(+) entry during phase 0, the AP time course is determined by the
      balance between inward depolarizing currents, carried mainly by Na(+) and Ca(2+),
      and outward repolarizing currents carried mainly by K(+). K(+) currents play a
      major role in repolarization. The loss of a K(+) current can impair
      repolarization, but there is a redundancy of K(+) currents so that when one K(+)
      current is dysfunctional, other K(+) currents increase to compensate, a
      phenomenon called 'repolarization reserve'. Repolarization reserve protects
      repolarization under conditions that increase inward current or reduce outward
      current, threatening the balance that governs AP duration. This protection comes
      at the expense of reduced repolarization reserve, potentially resulting in
      unexpectedly large AP prolongation and arrhythmogenesis, when an additional
      repolarization-suppressing intervention is superimposed. The critical role of
      appropriate repolarization is such that cardiac rhythm stability can be impaired
      with either abnormally slow or excessively rapid repolarization. In cardiac
      disease states such as heart failure and atrial fibrillation (AF), changes in ion
      channel properties appear as part of an adaptive response to maintain function in
      the face of disease-related stress on the cardiovascular system. However, if the
      stress is maintained the adaptive ion channel changes may themselves lead to
      dysfunction, in particular cardiac arrhythmias. The present article reviews ionic
      remodelling of cardiac repolarization, and focuses on how potentially adaptive
      repolarization changes with congestive heart failure and AF can have
      arrhythmogenic consequences.

PMID- 18826963
TI  - PROKR2 missense mutations associated with Kallmann syndrome impair receptor
      signalling activity.
AB  - Kallmann syndrome (KS) combines hypogonadism due to gonadotropin-releasing
      hormone deficiency, and anosmia or hyposmia, related to defective olfactory bulb
      morphogenesis. In a large series of KS patients, ten different missense mutations
      (p.R85C, p.R85H, p.R164Q, p.L173R, p.W178S, p.Q210R, p.R268C, p.P290S, p.M323I,
      p.V331M) have been identified in the gene encoding the G protein-coupled receptor
      prokineticin receptor-2 (PROKR2), most often in the heterozygous state. Many of
      these mutations were, however, also found in clinically unaffected individuals,
      thus raising the question of their actual implication in the KS phenotype. We
      reproduced each of the ten mutations in a recombinant murine Prokr2, and tested
      their effects on the signalling activity in transfected HEK-293 cells, by
      measuring intracellular calcium release upon ligand-activation of the receptor.
      We found that all mutated receptors except one (M323I) had decreased signalling
      activities. These could be explained by different defective mechanisms. Three
      mutations (L173R, W178S, P290S) impaired cell surface-targeting of the receptor.
      One mutation (Q210R) abolished ligand-binding. Finally, five mutations (R85C,
      R85H, R164Q, R268C, V331M) presumably impaired G protein-coupling of the
      receptor. In addition, when wild-type and mutant receptors were coexpressed in
      HEK-293 cells, none of the mutant receptors that were retained within the cells
      did affect cell surface-targeting of the wild-type receptor, and none of the
      mutant receptors properly addressed at the plasma membrane did affect wild-type
      receptor signalling activity. This argues against a dominant negative effect of
      the mutations in vivo.

PMID- 18826965
TI  - The retroperitoneal approach combined with epidural anesthesia reduces morbidity
      in elective infrarenal aortic aneurysm repair.
AB  - In elective open infrarenal aortic aneurysm repair the surgical approach and the
      use of epidural anesthesia (EDA) may determine patients' outcome. Hence we
      analyzed our results after elective open aneurysm repair in the light of the
      surgical approach and the use of EDA. Retrospective analysis of a prospective
      data base. From December 2005 to April 2008, 125 patients with infrarenal aortic
      aneurysm underwent elective open repair. Patients were divided into four groups:
      retro- and transperitoneal approach with and without epidural anesthesia (RP+/
      EDA and TP+/-EDA). In terms of age, sex, aneurysm diameter, ASA score and
      clamping time all groups were comparable. In the retroperitoneal groups
      significantly more tube grafts were implanted (63 vs. 27; P=0.001). The rate of
      surgical complications did not differ between the groups. The RP+EDA group had
      the lowest rate of postoperative assisted mechanical ventilation (5.1% vs. 35.7%;
      P=0.002) and medical complications (17.9% vs. 42.8%; P=0.032). Concerning
      frequency of surgical complications, the retroperitoneal incision was comparable
      to the transperitoneal approach in infrarenal aortic reconstruction.
      Supplementation with EDA resulted in a decreased rate of postoperative assisted
      mechanical ventilation and in lower morbidity rates.

PMID- 18826966
TI  - To-and-fro pattern: an indication of flow competition or a sign of incompetent
      coronary anastomosis?
AB  - To-and-fro pattern in pulse Doppler wave form has been considered a sign of flow
      competition at the coronary anastomosis. However, this flow pattern is not
      sufficient to judge whether there is no construction errors in the anastomosis
      itself. We report a usefulness of the high-frequency ultralinear transducer when
      used with pulse Doppler because it allows the visualization of the shapes of the
      anastomosis and each vessel, quantification of the flow, and elucidation of flow
      characteristics. This transducer can be applied to the management of suspected
      flow competition because, with pulse Doppler waveforms of graft flow and color
      Doppler images, it allows the detection of the diastolic-dominant flow pattern,
      good anastomotic shape, and smooth flow in the graft and the target vessel after
      the native vessel is clamped.

PMID- 18826967
TI  - Long-term efficiency of endoscopic thoracic sympathicotomy: survey 10 years after
      surgery.
AB  - Immediate and short-term results of endoscopic thoracic sympathectomy (ETS) for
      primary hyperhidrosis are good. Adverse effects have been identified clearly and
      are supposed to decrease with time. In this institutional report, the long-term
      results of ETS with regard to efficacy, side effects and patient satisfaction are
      presented. Fifteen patients were included and mean follow-up time was 12+/-2
      years. ETS success rate, rate of compensatory sweating and degree of patient
      satisfaction were assessed. We detected 8 patients (53%) complaining about a
      decent to moderate recurrence of hand sweating and compensatory and gustatory
      sweating were observed in 9 (60%) and 5 (33%) patients, respectively. Reported
      side effects related to surgery were paresthesias of the upper limb and the
      thoracic wall in 8 patients (53%) and recurrent pain in the axillary region in
      one. At an average 12 years after surgery, 47% of patients were satisfied with
      the treatment results, 40% were disappointed. Six patients (40%) affirmed they
      would ask for the operation if it were to be redone. Our findings indicate that
      results of ETS deteriorate and compensatory sweating does not improve with time.
      It is mandatory to inform patients of the potential long-term adverse effects
      before surgery.

PMID- 18826968
TI  - After the master settlement agreement: targeting and exposure of youth to
      magazine tobacco advertising.
AB  - Targeting and exposure of youth to magazine advertising of tobacco products is
      associated with increased smoking initiation. National magazine advertising and
      youth exposure declined in the period following the Master Settlement Agreement
      (MSA). However, tobacco companies continued targeting youth with brands that were
      popular among them through magazine advertising and placement of ads in magazines
      with high youth readership. Existing restrictions, followed by enforcement
      through litigation, have achieved a marked reduction in overall magazine
      advertising but may be less adequate compared with pending federal legislation to
      fully protect youth from the marketing of tobacco products designed to appeal to
      them.

PMID- 18826969
TI  - What is spared by fetal brain-sparing? Fetal circulatory redistribution and
      behavioral problems in the general population.
AB  - Intrauterine growth restriction has been linked to infant behavioral problems.
      While typically only birth weight is examined, here the authors assessed fetal
      circulatory redistribution, also called the "brain-sparing effect," which is a
      fetal adaptive reaction to placental insufficiency. They aimed to investigate
      whether fetal circulatory redistribution protects against behavioral problems.
      Within the Generation R Study (Rotterdam, the Netherlands, 2003-2007), fetal
      circulation variables for the umbilical artery and the middle and anterior
      cerebral arteries were assessed with Doppler ultrasound in late pregnancy. Ratios
      between placental resistance and cerebral resistance were related to behavioral
      problems, as measured by the Child Behavior Checklist, in 935 toddlers aged 18
      months. The umbilical/anterior cerebral ratio was associated with the Total
      Problems summary score from the Child Behavior Checklist (per standard-deviation
      increase, odds ratio = 1.2, 95% confidence interval: 1.0, 1.5). Children with
      higher umbilical/anterior cerebral ratios had higher risks of internalizing
      problems, emotional reactivity, somatic complaints, and attention problems. A
      high umbilical/middle cerebral ratio was related to higher scores on the
      Internalizing and Somatic Complaints scales. The authors conclude that infants
      with circulatory redistribution in gestation are more likely to have behavioral
      problems. This suggests that "brain-sparing" does not completely spare the brain
      and indicates underlying pathology with consequences for later behavior.

PMID- 18826970
TI  - Establishment of glutamine synthetase of Mycobacterium smegmatis as a protein
      acetyltransferase utilizing polyphenolic acetates as the acetyl group donors.
AB  - Acetoxy Drug: Protein Transacetylase (TAase) mediating the transfer of acetyl
      group(s) from polyphenolic acetates (PA) to certain functional proteins in
      mammalian cells was identified by our earlier investigations. TAase activity was
      characterized in the cell lysates of Mycobacterium smegmatis and the purified
      protein was found to have M(r) 58,000. TAase catalysed protein acetylation by a
      model acetoxy drug 7,8-diacetoxy-4-methylcoumarin (DAMC) was established by the
      demonstration of immunoreactivity of the acetylated target protein with an anti
      acetyllysine antibody. The specificity of the TAase of M. smegmatis (MTAase) to
      various acetoxycoumarins was found to be in the order DAMC > 7-AMC > 6-AMC > 4-AC
      > 3-AC > ABP. Also, the N-terminal sequence of purified MTAase was found to
      perfectly match with glutamine synthetase (GS) of M. smegmatis. The identity of
      MTAase with GS was confirmed by the observation that the purified MTAase as well
      as the purified recombinant GS exhibited all the properties of GS. The finding
      that purified Escherichia coli GS was found to have substantial TAase activity
      highlighted the TAase function of GS in other bacteria. These results
      conclusively established for the first time the protein acetyltransferase
      function of GS of M. smegmatis.

PMID- 18826971
TI  - The scaffold protein c-Jun NH2-terminal kinase-associated leucine zipper protein
      regulates cell migration through interaction with the G protein G(alpha 13).
AB  - Scaffold proteins for MAP kinase (MAPK) signalling modules play an important role
      in the specific and efficient signal transduction of the relevant MAPK cascades.
      Here, we investigated the function of the scaffolding protein c-Jun NH(2)
      terminal kinase (JNK)-associated leucine zipper protein (JLP) by depleting it in
      cultured cells using a short hairpin RNA (shRNA) against human JLP. HeLa and DLD
      1 cells stably expressing the shRNA showed a defect in cell migration. The re
      expression of full-length shRNA-resistant mouse JLP rescued the impaired cell
      migration of the JLP-depleted HeLa cells; whereas, a C-terminal deletion mutant
      of mouse JLP, which failed to bind the G protein G(alpha13), showed little or no
      effect on the cell migration defect. Furthermore, although a constitutively
      active G(alpha13) enhanced the migration of control HeLa cells, the G(alpha13)
      induced cell migration was significantly suppressed in the JLP-depleted HeLa
      cells. Taken together, these results suggest that JLP regulates cell migration
      through an interaction with G(alpha13).

PMID- 18826973
TI  - Actions speak louder than words.

PMID- 18826972
TI  - Effect of calcium-sensing receptor activation in models of autosomal recessive or
      dominant polycystic kidney disease.
AB  - BACKGROUND: Antagonists of relevant Gs protein-coupled and agonists of relevant
      Gi protein-coupled receptors lower renal cAMP and inhibit growth of renal cysts
      in animal models of human ARPKD (PCK rat) and/or ADPKD (Pkd2(-/WS25) mouse). A
      calcium-sensing receptor (CaR) is expressed in various tubular segments and
      couples to Gq, thereby activating phospholipase Cgamma, InsP3 generation and
      calcium mobilization from intracellular stores, and Gi proteins. By both
      mechanisms, CaR activation could lower intracellular cAMP and inhibit renal cyst
      growth. METHODS: PCK rat and Pkd2(-/WS25) mouse littermates were fed rodent chow
      without or with R-568, a type 2 calcimimetic, at a concentration of 0.05% or 0.1%
      between 3 and 10 or 16 weeks of age. Histomorphometric analysis was performed
      with Meta-Morph software. Western analysis and immunohistochemical staining were
      performed using antibodies for aquaporin-2, urea transporter UT-A1 and CaR.
      Northern blot hybridization was used to quantify the expression of vasopressin V2
      receptor and aquaporin 2 mRNAs. Cyclic AMP was measured using an enzyme
      immunoassay kit. RESULTS: R-568 had no effect on kidney weight, cyst volume,
      plasma BUN concentration or severity of the polycystic liver disease. A
      significant reduction in renal interstitial fibrosis was detected in PCK rats,
      but not in Pkd2(-/WS25) mice. R-568 administration, as anticipated, resulted in
      hypocalcemia and hyperphosphatemia, and significant increases in urine output,
      osmolar clearance, and urinary excretions of sodium, potassium and calcium.
      CONCLUSIONS: CaR activation had no detectable effect on cystogenesis in models of
      autosomal recessive or dominant polycystic kidney disease. The lack of protective
      effect could be due to the absence of CaR in the outer medullary and cortical
      collecting ducts, the reduction in extracellular calcium and the unaffected
      levels of renal cAMP and renal expression of cAMP-dependent genes. A possible
      beneficial effect on interstitial fibrosis deserves further study at more
      advanced stages of the disease.

PMID- 18826974
TI  - The emperor's new constitution.

PMID- 18826975
TI  - US health groups protest against proposed government "conscience rule".

PMID- 18826976
TI  - Patient challenges trust's right to deprive her of NHS treatment for buying drugs
      privately.

PMID- 18826977
TI  - World leaders pledge extra $3bn to combat malaria.

PMID- 18826978
TI  - How patients rate doctors.

PMID- 18826979
TI  - Antibiotic use in community in Northern Ireland is a third higher than in
      England.

PMID- 18826980
TI  - Endovascular management of hoarseness due to a thoracic aneurysm: case report and
      review of the literature.
AB  - Although uncommon, hoarseness can be a presenting symptom of a thoracic aneurysm.
      We present a case of a 67-year-old man with hoarseness, subsequently found to
      have left vocal paralysis. On workup, a computed tomography scan demonstrated a
      saccular thoracic aneurysm compressing the recurrent laryngeal nerve at the
      aortopulmonary window. About 6 months after treatment with an endovascular stent
      graft, the aneurysm sac decreased in size and hoarseness resolved without further
      surgical intervention. Although uncommonly mentioned as an indication for
      surgery, hoarseness from a thoracic aneurysm can be successfully managed with
      endovascular stent grafting.

PMID- 18826981
TI  - Cerebral hyperperfusion after carotid stenting: a transcranial doppler and SPECT
      study.
AB  - AIM: To document the incidence of symptomatic cerebral hyperperfusion after
      carotid stenting and to determine possible predisposing factors. METHODS: A
      prospective study of 29 consecutive patients undergoing carotid stenting. All
      patients underwent 1) brain computed tomography scan and magnetic resonance
      imaging, 2) transcranial Doppler including assessment of cerebrovascular
      reactivity of the ipsilateral middle cerebral artery and 3) 99m hexamethyl
      propyleneamine oxime brain single photon emission computed tomography, before and
      after the procedure. RESULTS: A total of 5 patients developed adverse
      neurological events, 4 of them transient. Cerebral hyperperfusion was documented
      in two of these (6.9%). Both had exhausted cerebrovascular reactivity in the
      preoperative transcranial Doppler examination. No consistent pattern of
      interhemispheric asymmetry in brain perfusion was found in these patients.
      CONCLUSIONS: Symptomatic cerebral hyperperfusion is not uncommon after carotid
      stenting. There seems to be a link between exhausted cerebrovascular reactivity
      of the ipsilateral middle cerebral artery and increased risk of cerebral
      hyperperfusion.

PMID- 18826982
TI  - Cessation of epilepsy in an 8-year-old girl following removal of carotid body
      paraganglioma.
AB  - We present a case of an 8-year-old girl with established focal epilepsy, whose
      fits resolved permanently after excision of a carotid body paraganglioma.

PMID- 18826983
TI  - Endovascular abdominal aortic aneurysm repair: a community hospital's experience.
AB  - Endovascular abdominal aortic aneurysm repair (EVAR) has become the first-line
      approach for the treatment of abdominal aortic aneurysms. Outcomes outside of
      tertiary care settings remain unknown. The purpose of this study is to report the
      midterm outcomes of EVAR in a community hospital. A retrospective review of 75
      elective, consecutive EVARs performed at a single nonacademic community hospital
      was performed. There were no conversions to open repair during or after
      endovascular repair. The mean follow-up was 18 months. There were no
      postoperative ruptures or aneurysm-related deaths. At 24 months, freedom from
      aneurysm-related death was 100%, freedom from secondary interventions was 91%,
      and freedom from endoleak was 69%. EVAR in the community setting is a safe and
      durable procedure, even in a medically high-risk population. Comparable outcomes
      can be achieved to tertiary care centers, in carefully selected patients with
      favorable anatomy.

PMID- 18826984
TI  - Mental health clinicians' beliefs about medicines, attitudes, and expectations of
      improved medication adherence in patients.
AB  - Nonadherence to antipsychotic medications remains a major factor in poor clinical
      outcomes. This study sought to identify clinician beliefs about patients who do
      not adhere to treatment, the clinicians' own beliefs about medicines, and the
      impact of beliefs on efforts to enhance patient adherence. In total, 292
      clinicians responded to an anonymous questionnaire that included questions about
      their beliefs and their efforts to enhance adherence. Results indicated that
      clinicians' beliefs about their own adequacy to enhance adherence significantly
      predicted actual efforts to enhance adherence. Both pessimism about outcomes and
      empathy for the patient predicted outcome expectancy. It was concluded that
      enhancing clinicians' beliefs about working with nonadherent patients is a
      potentially important ingredient in efforts to improve patient adherence.

PMID- 18826985
TI  - Comment on 'Comparison of operator radiation exposure with optimized radiation
      protection devices during coronary angiograms and ad hoc percutaneous coronary
      interventions by radial and femoral routes'.

PMID- 18826986
TI  - Endocardial fibroelastosis in dilated cardiomyopathy in a 28-year-old transplant
      recipient.

PMID- 18826987
TI  - The value of fractional and coronary flow reserve in predicting myocardial
      recovery in patients with previous myocardial infarction.
AB  - AIMS: The aim of the study was to evaluate the relation between fractional flow
      reserve (FFR) and simultaneously evaluated coronary flow reserve by
      thermodilution (CFRthermo), with the improvement of left ventricular (LV)
      function in patients with previous myocardial infarction (MI) undergoing
      percutaneous coronary intervention (PCI). METHODS AND RESULTS: Study population
      consisted of 46 patients (mean age 53 +/- 7 years; 36 male) with previous MI and
      significant coronary stenosis undergoing PCI of infarct-related coronary artery.
      In all patients, we evaluated FFR and CFRthermo by single pressure/thermo wire
      during maximal hyperaemia before and immediately after PCI. We performed
      echocardiographic assessment of LV ejection fraction before and 6 months after
      PCI. Dobutamine stress echocardiography test was also performed before PCI. LV
      functional improvement was observed in 33/46 (72%) of patients. In patients with
      LV functional recovery in comparison with patients with no recovery, there was a
      significant difference in FFR before PCI (0.56 +/- 0.14 vs. 0.70 +/- 0.07, P <
      0.001), improvement of FFR (0.35 +/- 0.14 vs. 0.21 +/- 0.07, P < 0.001),
      improvement of CFRthermo (1.3 +/- 0.6 vs. 0.5 +/- 0.3, P < 0.001), and CFRthermo
      after PCI (2.6 +/- 0.7 vs. 2.0 +/- 0.4, P < 0.001). When only parameters
      evaluated before PCI were taken into account, FFR before angioplasty (P = 0.001)
      and dobutamine-assessed viability (P = 0.006) were the most significant
      multivariate predictors of myocardial recovery. When all significant univariate
      parameters were evaluated, the most significant independent predictors for
      improvement in myocardial function were the improvement of CFRthermo during
      angioplasty (P < 0.001) and FFR before angioplasty (P = 0.002). CONCLUSION:
      Simultaneous evaluation of FFR and CFRthermo provide significant complementary
      data on the improvement in myocardial function in patients with previous MI.
      However, the evaluation of FFR before angioplasty identifies viable myocardium
      that may recover following revascularization and may be used as an alternative to
      non-invasive testing.

PMID- 18826988
TI  - Comparison of four tests to assess inhibition of platelet function by clopidogrel
      in stable coronary artery disease patients.
AB  - AIMS: We investigated the comparability of platelet function tests in quantifying
      platelet inhibition achieved by clopidogrel. METHODS AND RESULTS: This pre
      specified substudy of a randomized, double-blind trial included 116 patients with
      stable coronary artery disease requiring diagnostic angiography. Patients
      received clopidogrel for 1 (300 or 600 mg) or 7 days (300 + 75 or 150 mg daily)
      before the procedure. Blood samples obtained before clopidogrel initiation and
      before diagnostic coronary angiography were assayed using light transmission
      aggregometry [adenosine diphosphate (ADP) 5 and 20 microM as the agonist], whole
      blood aggregometry (ADP 5 and 20 microM), PFA-100 (Collagen-ADP cartridge), and
      VerifyNow P2Y12. Although all assays studied were found sensitive to clopidogrel
      ingestion, none could distinguish categorically between patients who had, or not,
      ingested clopidogrel. Agreement between assays to identify patients with
      insufficient inhibition of platelet aggregation by clopidogrel was low.
      CONCLUSION: The assessment of platelet function inhibition by clopidogrel is
      highly test-specific. Decision to increase clopidogrel dosage may vary on the
      basis of the assay used, thus highlighting the need for unambiguous guidelines
      with respect to assay selection, as platelet function assays are not
      interchangeable. At present, platelet function testing evaluating clopidogrel
      efficacy cannot be recommended in routine clinical practice.

PMID- 18826989
TI  - Hormone therapy and risk of myocardial infarction: a national register study.
AB  - AIM: To assess the risk of myocardial infarction (MI) as a result of hormone
      therapy (HT), with focus on the influence of age, duration of HT, various
      regimens and routes, progestagen type, and oestrogen dose. METHODS AND RESULTS:
      All healthy Danish women (n = 698,098, aged 51-69) were followed during 1995
      2001. On the basis of a central prescription registry, daily updated national
      capture on HT was determined. National Registers identified 4947 MI incidents.
      Poisson regression analyses estimated rate ratios (RRs). Overall, we found no
      increased risk [RR 1.03 (95% CI: 0.95-1.11)] of MI with the current HT compared
      with women who never used HT; age-stratified RR among women aged 51-54, 55-59, 60
      64, and 65-69 years were 1.24 (1.02-1.51), 0.96 (0.82-1.12), 1.11 (0.97-1.27),
      and 0.92 (0.80-1.06), respectively. An increasing risk with longer duration was
      found for younger women, which was not observed with older age groups. In all age
      groups, the highest risk of MI was found with continuous HT regimen. No increased
      risk was found with unopposed oestrogen, cyclic combined therapy, or tibolone.
      Significantly lower risk was found with dermal route than oral unopposed
      oestrogen therapy (P = 0.04). No associations were found with progestagen type or
      oestrogen dose. CONCLUSION: In a National cohort study, we found that HT regimen
      and route of application could modify the influence of HT on the risk of MI.

PMID- 18826990
TI  - Drinking alcohol for medicinal purposes by people aged over 75: a community-based
      interview study.
AB  - BACKGROUND: Physicians often encounter patients using alcohol as self-medication,
      but studies on community level are scarce. Because of alcohol-medicine
      interactions, it is important to know also all self-medication used. OBJECTIVE:
      To describe alcohol use as self-medication by people aged over 75 years. METHODS:
      The home-dwelling elderly (n = 699) among a random sample of 1000 subjects from
      the total population of individuals aged 75 years or more in the city of Kuopio,
      Finland, were interviewed about their alcohol consumption and use as self
      medication and also about their lifestyle habits, medicaments and diseases. A
      geriatrician checked their medical records for medical conditions. RESULTS: Half
      of the subjects consumed alcohol, and 40% of them used alcohol for medicinal
      purposes. This was equally common in females and males. The quantity used was
      half a unit or less in 68% of cases. Brandy and other spirits were the most
      commonly used beverages, and heart and vascular disorders (38%), sleep disorders
      (26%) and mental problems (23%) were the commonest reasons for use. The study
      found altogether 84 persons who responded negatively to the question about
      alcohol consumption but later reported using alcohol as self-medication.
      CONCLUSIONS: Drinking alcohol for medicinal purposes is common among the aged in
      Finland. Some people, especially older women, may find it easier to discuss their
      alcohol consumption in the context of medicinal use. Physicians have to consider
      the possible risks of alcohol associated with concomitant medical conditions and
      interactions of alcohol with medicines.

PMID- 18826991
TI  - Determinants of healthy eating: motivation, abilities and environmental
      opportunities.
AB  - BACKGROUND: In order to promote healthful nutrition, insight is needed in the
      behavioural determinants of nutrition behaviours. Most research on behavioural
      determinants has been restricted to individual-level motivational factors.
      However, health behaviour is influenced by individual motivation and abilities,
      as well as environmental opportunities. OBJECTIVE: To provide an overview of
      motivation, ability and opportunity-related potential determinants of nutrition
      behaviours and of the evidence for associations of potential environmental
      determinants with nutrition behaviour. METHOD: A narrative review informed by a
      series of six systematic reviews including more than 400 original studies and
      recent original studies on associations of environmental factors with nutrition
      behaviours. RESULTS: Although the number of studies on potential environmental
      determinants of nutrition as well as physical activity behaviour has increased
      steeply over the last decades, these include only few well-designed studies with
      validated measures. Preliminary evidence from the available systematic reviews
      indicates that social support and modelling, availability and accessibility of
      healthy and less healthy foods as well as socio-economic status are important for
      nutrition behaviours; schools and worksites offer good settings for improving
      healthful nutrition opportunities. CONCLUSION: Although the evidence to date is
      inconclusive due to lack of well-designed studies, specific social-cultural,
      physical and economical environmental factors appear of importance for healthful
      nutrition.

PMID- 18826992
TI  - Co-morbidity obese children in family practice in The Netherlands: the results of
      a pilot study.
AB  - OBJECTIVES: The aim of this pilot study was to assess the prevalence of co
      morbidity in obese children. Particular emphasis was on cardiovascular risk.
      METHOD: In this retrospective, cross-sectional, observational study the data of
      155 obese children, who visited a paediatric obesity outdoor clinic, have been
      studied. RESULTS: In all, 92% of the population had at least one cardiovascular
      risk factor. In all, 48% showed a high systolic and 9% a high diastolic blood
      pressure, while 18% had an increased fasting glucose. In 60%, we diagnosed
      insulin resistance: the homeostasis model assessment was elevated. DISCUSSIONS:
      The prevalence of high blood pressure, dyslipidaemia, abnormal fasting glucose
      and insulin resistance are high in this retrospective study. Outcomes of foreign
      studies on this object are difficult to compare because various populations and
      cut-off points are used. A new, prospective, study will be conducted to asses the
      prevalence of co-morbidity in obese children in general practice.

PMID- 18826993
TI  - Perspectives on obesity and sweeteners, folic acid fortification and vitamin D
      requirements.
AB  - This review summarizes three controversial areas of clinical practice that were
      discussed in many articles that appeared in the American Journal of Clinical
      Nutrition during the author's tenure as editor in chief. Controversy 1-obesity
      and high-fructose corn syrup. The increased frequency of obesity in the US is
      paralleled by increasing annual consumption of high-fructose corn syrup, an
      extracted sweetener that is routinely added to soft drinks and to many processed
      foods in the US diet. Metabolic studies implicate increased fructose consumption
      in increased body fat and obesity and with increased circulating triglyceride
      levels and hypercholesterolaemia in children. Controversy 2-folic acid
      fortification and supplements. Together with widespread use of supplemental
      multivitamins, fortification of the US diet with folic acid has resulted in high
      serum folate levels in much of the population, which may be associated with
      increased risk of cognitive decline in ageing people with low vitamin B12 status,
      decreased natural killer T-cell immune function and increased risk of recurrent
      advanced precancerous colorectal adenomas and breast cancer. Controversy 3
      recommended intakes of vitamin D. Levels of serum 25(OH)D sufficient for fracture
      prevention are at least 75 nmol/l (30 ng/ml) but cannot be achieved by the
      current recommended dietary intakes in the US. A recent fracture risk prevention
      trial showed that the 4-year incidence of all cancers was reduced in US women who
      received high supplemental doses of both calcium and vitamin D.

PMID- 18826994
TI  - Women's views and experiences of antidepressants as a treatment for postnatal
      depression: a qualitative study.
AB  - BACKGROUND: Antidepressants are frequently prescribed by GPs for postnatal
      depression (PND). Patients, however, may be reluctant to take medication and have
      concerns that result in poor treatment adherence. Few studies have explored
      women's views and experiences of antidepressants as a treatment for PND. GPs need
      to understand women's views and experiences if they are to address their concerns
      and improve treatment adherence. OBJECTIVE: To explore women's views and
      experiences of antidepressants as a treatment for PND. METHODS: In-depth
      interviews with 27 women in three UK cities who had been diagnosed with PND and
      taken part in a randomized controlled trial. During the trial, participants could
      receive antidepressants and/or non-directive counselling. Data were analysed
      thematically. RESULTS: Most participants stated that they had held negative views
      towards antidepressants at the time of randomization. Some participants reported
      that, over the course of their illness, through time and contact with others,
      including health professionals, their views towards antidepressants had changed
      and that they had gone on to take medication. Most interviewees who had taken
      antidepressants reported benefits, although some remained concerned about taking
      medication. CONCLUSION: Women's views of antidepressants can change in response
      to their treatment options and experiences, the views of friends and relatives
      and their contact with health professionals. GPs should assess women's concerns
      about antidepressants prior to prescribing them for PND and should provide
      regular follow-up for women on medication. This should lead to greater treatment
      adherence and thus earlier resolution of symptoms.

PMID- 18826995
TI  - Renal medullary 11 beta-hydroxysteroid dehydrogenase type 1 in Dahl salt
      sensitive hypertension.
AB  - The Dahl salt-sensitive rat is a widely used model of human salt-sensitive forms
      of hypertension. The kidney plays an important role in the pathogenesis of Dahl
      salt-sensitive hypertension, but the molecular mechanisms involved remain a
      subject of intensive investigation. Gene expression profiling studies suggested
      that 11 beta-hydroxysteroid dehydrogenase type 1 might be dysregulated in the
      renal medulla of Dahl salt-sensitive rats. Additional analysis confirmed that
      renal medullary expression of 11 beta-hydroxysteroid dehydrogenase type 1 was
      downregulated by a high-salt diet in SS-13BN rats, a consomic rat strain with
      reduced blood pressure salt sensitivity, but not in Dahl salt-sensitive rats. 11
      beta-Hydroxysteroid dehydrogenase type 1 is known to convert inactive 11
      dehydrocorticosterone to active corticosterone. The urinary corticosterone/11
      dehydrocorticosterone ratio as well as urinary excretion of corticosterone was
      higher in Dahl salt-sensitive rats than in SS-13BN rats. Knockdown of renal
      medullary 11 beta-hydroxysteroid dehydrogenase type 1 with small-interfering RNA
      attenuated the early phase of salt-induced hypertension in Dahl salt-sensitive
      rats and reduced urinary excretion of corticosterone. Knockdown of 11 beta
      hydroxysteroid dehydrogenase type 1 did not affect blood pressure in SS-13BN
      rats. Long-term attenuation of salt-induced hypertension was achieved with small
      hairpin RNA targeting renal medullary 11 beta-hydroxysteroid dehydrogenase type
      1. In summary, we have demonstrated that suppression of 11 beta-hydroxysteroid
      dehydrogenase type 1 expression in the renal medulla attenuates salt-induced
      hypertension in Dahl salt-sensitive rats.

PMID- 18826996
TI  - Network analysis of temporal effects of intermittent and sustained hypoxia on rat
      lungs.
AB  - The molecular networks underlying the lung response to hypoxia are not fully
      understood. We employed systems biology approaches to study temporal effects of
      intermittent or sustained hypoxia on gene expression in rat lungs. We obtained
      gene expression profiles from rats exposed to intermittent or sustained hypoxia
      lasting 0-30 days and identified differentially expressed genes, their patterns,
      biological processes, and regulatory networks critical for lung response to
      intermittent or sustained hypoxia. We validated selected genes with quantitative
      real-time PCR. Intermittent and sustained hypoxia induced two distinct sets of
      genes in rat lungs that displayed different temporal expression patterns.
      Intermittent hypoxia induced genes mostly involved in ion transport and
      homeostasis, neurological processes, and steroid hormone receptor activity, while
      sustained hypoxia induced genes principally participating in immune responses.
      The intermittent hypoxia-activated network suggested a role for cross talk
      between estrogen receptor 1 (ESR1) and other key proteins in hypoxic responses.
      The sustained hypoxia-activated network was indicative of vascular remodeling and
      pulmonary hypertension. We confirmed the temporal expression changes of 12 genes
      (including the Esr1 gene and 4 ESR1 target genes) in intermittent hypoxia and 8
      genes in sustained hypoxia with quantitative real-time PCR. CONCLUSIONS:
      intermittent and sustained hypoxia induced distinct gene expression patterns in
      rat lungs. The functional characteristics of genes activated by these two
      distinct perturbations suggest their roles in the downstream physiological
      effects of intermittent and sustained hypoxia. Our results demonstrate the
      discovery potential of applying systems biology approaches to the understanding
      of mechanisms underlying hypoxic lung response.

PMID- 18826997
TI  - Impact of screening kindreds for SDHD p.Cys11X as a common mutation associated
      with paraganglioma syndrome type 1.
AB  - CONTEXT AND OBJECTIVE: Germline mutations of the genes SDHB, SDHC, and SDHD
      predispose to paraganglioma syndromes. Mutation-specific counseling, risk
      assessment, and management recommendations ideally should be performed. Here, we
      provide data for a single common mutation of the SDHD gene. METHODS: The European
      American Pheochromocytoma-Paraganglioma Registry served as the source for
      unrelated index cases affected by pheochromocytoma or paraganglioma. Patients
      with the SDHD c.33 C-->A (p.Cys11X) germline mutations were reinvestigated by
      whole-body magnetic resonance imaging and 24-h urinary catecholamine assay. First
      degree relatives underwent genetic testing and those testing positive had same
      clinical investigations. Microsatellite analyses were used to test the hypothesis
      that all index cases were related and the mutation is a founding one. RESULTS:
      Sixteen index cases with the mutation SDHD p.Cys11X are registered. After testing
      their relatives, there were a total of 25 mutation carriers. We excluded seven
      subjects who inherited the mutation from the mother because of maternal
      imprinting. Thus, 18 mutation carriers were clinically affected. Among these 16
      (89%) had head and neck paragangliomas, six (33%) thoracic tumors, six (33%)
      extraadrenal retroperitoneal, and five (28%) intraadrenal. Of note, 16 (89%) had
      multiple tumors at first diagnosis, and one (5%) had signs of malignancy during
      follow-up. Overall penetrance was 100% at age 54. Haplotype analyses revealed
      evidence for a founder effect. CONCLUSIONS: The SDHD p.Cys11X mutation is a
      founding mutation associated with a high penetrance for paraganglial tumors of
      the skull base, neck, thorax, and retroperitoneum in the first four decades of
      life and, rarely, with malignancy.

PMID- 18826998
TI  - Rate of beta-cell destruction in type 1 diabetes influences the development of
      diabetic retinopathy: protective effect of residual beta-cell function for more
      than 10 years.
AB  - CONTEXT: Although residual beta-cell function delays the onset and progression of
      diabetic retinopathy in patients with type 1 diabetes, the rate of beta-cell
      destruction is variable. OBJECTIVE: The aim of the study was to clarify the
      influence of the rate of beta-cell destruction on the development and progression
      of diabetic retinopathy in type 1 diabetes. DESIGN: We performed a historical
      cohort study regarding residual beta-cell function and retinopathy. SETTING: The
      study was conducted in the outpatient clinic of a general hospital. PATIENTS: A
      total of 254 patients with type 1 diabetes participated. MAIN OUTCOME MEASURES:
      Serum C-peptide and fundus findings were evaluated longitudinally. RESULTS: The
      cumulative incidence of mild nonproliferative diabetic retinopathy was higher in
      the patients without detectable beta-cell function than in those with residual
      beta-cell function at 20, 15, and 10 yr after the onset of diabetes (P = 0.013, P
      = 0.006, and P = 0.048, respectively), but not at 5 yr after the onset (P =
      0.84). There were higher mean glycosylated hemoglobin values during the entire
      follow-up period in the patients without detectable beta-cell function at 20 and
      15 yr after the onset of diabetes (P = 0.030 and P = 0.042, respectively).
      Positivity for HLA-A24 and -DQA1 03, as well as the acute onset of diabetes, was
      associated with early beta-cell loss and also with early development of diabetic
      retinopathy. Cox proportional hazards analysis showed that undetectable beta-cell
      function at 20, 15, or 10 yr after the onset of diabetes was an independent risk
      factor for the development of diabetic retinopathy. CONCLUSIONS: Undetectable
      beta-cell function within 10 yr of the onset of type 1 diabetes is associated
      with the earlier occurrence of diabetic retinopathy.

PMID- 18826999
TI  - Prevention of diabetes in women with a history of gestational diabetes: effects
      of metformin and lifestyle interventions.
AB  - CONTEXT: A past history of gestational diabetes mellitus (GDM) confers a very
      high risk of postpartum development of diabetes, particularly type 2 diabetes.
      OBJECTIVE: The Diabetes Prevention Program (DPP) sought to identify individuals
      with impaired glucose tolerance (IGT) and intervene in an effort to prevent or
      delay their progression to diabetes. This analysis examined the differences
      between women enrolled in DPP with and without a reported history of GDM. DESIGN:
      The DPP was a randomized, controlled clinical trial. SETTING: The study was a
      multicenter, National Institutes of Health-sponsored trial carried out at 27
      centers including academic and Indian Health Services sites. PATIENTS: A total of
      2190 women were randomized into the DPP and provided information for past history
      of GDM. This analysis addressed the differences between those 350 women providing
      a past history of GDM and those 1416 women with a previous live birth but no
      history of GDM. INTERVENTIONS: Subjects were randomized to either standard
      lifestyle and placebo or metformin therapy or to an intensive lifestyle
      intervention. MAIN OUTCOMES: The primary outcome was the time to development of
      diabetes ascertained by semiannual fasting plasma glucose and annual oral glucose
      tolerance testing. Assessments of insulin secretion and insulin sensitivity were
      also performed. RESULTS: Whereas entering the study with similar glucose levels,
      women with a history of GDM randomized to placebo had a crude incidence rate of
      diabetes 71% higher than that of women without such a history. Among women
      reporting a history of GDM, both intensive lifestyle and metformin therapy
      reduced the incidence of diabetes by approximately 50% compared with the placebo
      group, whereas this reduction was 49 and 14%, respectively in parous women
      without GDM. These data suggest that metformin may be more effective in women
      with a GDM history as compared with those without. CONCLUSIONS: Progression to
      diabetes is more common in women with a history of GDM compared with those
      without GDM history despite equivalent degrees of IGT at baseline. Both intensive
      lifestyle and metformin are highly effective in delaying or preventing diabetes
      in women with IGT and a history of GDM.

PMID- 18827000
TI  - Regulation of islet hormone release and gastric emptying by endogenous glucagon
      like peptide 1 after glucose ingestion.
AB  - BACKGROUND: Exogenous administration of glucagon-like peptide (GLP)-1 improves
      glucose tolerance by stimulation of insulin secretion, inhibition of glucagon
      secretion, and delay of gastric emptying. It is not known which of these effects
      is involved in the action of endogenous GLP-1 to control blood glucose. To
      determine the role of endogenous GLP-1 on islet cell function and gastric
      emptying independent of variable glycemia, we clamped blood glucose before and
      during glucose ingestion with and without GLP-1 receptor blockade with exendin-[9
      39] (Ex-9). METHODS: There were 10 healthy subjects that participated in two
      experiments each, one a control and one with infusion of 750 pm/kg . min Ex-9.
      Subjects consumed 75 g oral glucose solution mixed with d-xylose and (13)C
      glucose while their blood glucose levels were held fixed at approximately 8.9
      mmol/liter. RESULTS: Plasma insulin levels during hyperglycemia alone were
      similar in the two studies (control, 282.5 +/- 42 vs. Ex-9, 263.8 +/- 59
      pmol/liter) but were reduced by approximately 30% by Ex-9 after glucose ingestion
      (control, 1154 +/- 203 vs. Ex-9, 835 +/- 120 pmol/liter; P < 0.05). Blocking the
      action of endogenous GLP-1 caused an approximate 80% increase in postprandial
      glucagon concentrations. The appearance of ingested d-xylose in the blood was not
      affected by Ex-9, suggesting that postprandial secretion of GLP-1 has only
      minimal effects on gastric emptying of oral glucose. CONCLUSIONS: These findings
      indicate that GLP-1 is an incretin in healthy humans at modestly
      supraphysiological blood glucose levels. The primary effect of GLP-1 to regulate
      oral glucose tolerance is mediated by effects on islet hormones and not on
      gastric emptying.

PMID- 18827001
TI  - Constant adaptation of bone to current physical activity level in men: a 12-year
      longitudinal study.
AB  - CONTEXT: A high peak bone mineral density (BMD; grams per square centimeter)
      could reduce the risk of osteoporosis related fractures later in life. OBJECTIVE:
      This 12-yr longitudinal study investigated whether a high BMD from previous high
      physical activity is maintained with reduced activity later in life. DESIGN: This
      was a longitudinal study. PARTICIPANTS: Three groups were investigated with a
      mean age of 17 yr at baseline; 51 athletes who stopped their active careers
      during follow-up (former athletes), 16 who were active throughout follow-up
      (active athletes), and 25 controls. MAIN OUTCOME MEASURES: BMD of the femoral
      neck, total body, and lumbar spine were examined five times during the 12-yr
      follow-up period. RESULTS: After adjustment for age, weight, and height, the
      former athletes were found to have higher BMD at all sites at every follow-up
      visit except the last one, when compared with controls (P < 0.05). The active
      athletes were found to have significantly higher BMD at all measured locations
      when compared with controls throughout the entire study (P < 0.05). From the
      first to the final follow-up visit, the former athletes were found to have lost
      more femoral neck BMD than both the active athletes (mean difference, 0.12
      g/cm(2); P = 0.003) and controls (mean difference 0.08 g/cm(2); P = 0.02).
      CONCLUSION: This study suggests that BMD constantly adapts to the present
      physical activity levels in young men. Thus, increased BMD due to previous high
      physical activity may not prevent osteoporosis in later years.

PMID- 18827002
TI  - Familial risks for hospitalization with endocrine diseases.
AB  - CONTEXT: Familial clustering of a disease is an indicator of a possible heritable
      cause. In the era of genome scans, the consideration of data on heritability
      should be important in the assessment of the likely success of the scans. OBJECT:
      The objective of the study was to carry out a family study on nonthyroid
      endocrine diseases to search familial clustering of these diseases beyond the
      known syndromes. DESIGN AND SETTING: The Swedish Multigeneration Register on 0-
      to 72-yr-old subjects was linked to the Hospital Discharge Register from years
      1964 to 2004. MAIN OUTCOME MEASURE: Standardized incidence ratios were calculated
      for offspring of affected parents and siblings by comparing with those whose
      relatives had no hospitalization for nonthyroid endocrine diseases. RESULTS: A
      total of 11,948 hospitalized cases and 443 familial cases were identified. The
      familial standardized incidence ratios were increased for parathyroid, pituitary,
      and adrenal hyperfunctions and hypofunctions, some findings consistent with known
      syndromes, most clearly that for adrenal cortical hypofunction showing recessive
      inheritance described for autoimmune polyendocrine syndrome 1. The sibling risks
      were very high for many diseases, but some of these affecting young individual
      may be due to bias caused by selective hospitalization. A high sibling risk
      observed for anterior pituitary hypofunction may represent a yet-unknown
      recessive syndrome. CONCLUSIONS: To our knowledge this is a first population
      based study on nonthyroid endocrine diseases. The results call for further
      studies to sort out the challengingly high sibling risk for many individual
      nonthyroid endocrine diseases, whether they are due to bias or possible recessive
      effects.

PMID- 18827003
TI  - A novel point mutation in the amino terminal domain of the human glucocorticoid
      receptor (hGR) gene enhancing hGR-mediated gene expression.
AB  - CONTEXT: Interindividual variations in glucocorticoid sensitivity have been
      associated with manifestations of cortisol excess or deficiency and may be partly
      explained by polymorphisms in the human glucocorticoid receptor (hGR) gene. We
      studied a 43-yr-old female, who presented with manifestations consistent with
      tissue-selective glucocorticoid hypersensitivity. We detected a novel, single,
      heterozygous nucleotide (G --> C) substitution at position 1201 (exon 2) of the
      hGR gene, which resulted in aspartic acid to histidine substitution at amino acid
      position 401 in the amino-terminal domain of the hGRalpha. We investigated the
      molecular mechanisms of action of the natural mutant receptor hGRalphaD401H.
      METHODS-RESULTS: Compared with the wild-type hGRalpha, the mutant receptor
      hGRalphaD401H demonstrated a 2.4-fold increase in its ability to transactivate
      the glucocorticoid-inducible mouse mammary tumor virus promoter in response to
      dexamethasone but had similar affinity for the ligand (dissociation constant =
      6.2 +/- 0.6 vs. 6.1 +/- 0.6 nm) and time to nuclear translocation (14.75 +/- 0.25
      vs. 14.25 +/- 1.13 min). The mutant receptor hGRalphaD401H did not exert a
      dominant positive or negative effect upon the wild-type receptor, it preserved
      its ability to bind to glucocorticoid response elements, and displayed a normal
      interaction with the glucocorticoid receptor-interacting protein 1 coactivator.
      CONCLUSIONS: The mutant receptor hGRalphaD401H enhances the transcriptional
      activity of glucocorticoid-responsive genes. The presence of the D401H mutation
      may predispose subjects to obesity, hypertension, and other manifestations of the
      metabolic syndrome.

PMID- 18827004
TI  - Prevalence of vertebral fractures in men with acromegaly.
AB  - CONTEXT: Data on osteoporotic fractures in acromegaly are limited. An increased
      prevalence of radiological vertebral fractures was already observed in
      postmenopausal women with active acromegaly. It is unknown whether this
      observation may reflect a more general increased risk of fractures in acromegaly.
      DESIGN: This was a cross-sectional study. SETTING: The study was conducted at
      referral centers. PATIENTS AND CONTROL SUBJECTS: Subjects included 40 males with
      acromegaly (25 patients with controlled disease and 15 patients with active
      disease) and 31 control males, with age and gonadal status comparable with the
      patients. INTERVENTIONS: Evaluation of vertebral fractures (quantitative
      morphometric analysis) and bone mineral density (BMD) at lumbar spine and total
      hip (dual energy X-ray absorptiometry) was done. MAIN OUTCOME MEASURE: Vertebral
      fractures were assessed. RESULTS: Although BMD was not significantly different
      between acromegalic patients and control subjects, the prevalence of vertebral
      fractures was higher in acromegalic patients as compared with the control
      subjects (57.5 vs. 22.6%; chi(2): 8.7; P = 0.003). Fractured and nonfractured
      acromegalic patients showed no significant difference in age and BMD Z-score.
      However, acromegalic patients with fractures had serum IGF-I values significantly
      higher and duration of active disease significantly longer with respect to
      patients without fractures. Moreover, patients with fractures showed
      significantly longer untreated hypogonadism as compared with patients without
      fractures. In a multivariate logistic regression analysis, the duration of active
      acromegaly was the only risk factor significantly correlated with the occurrence
      of fractures (odds ratio 1.1, confidence interval 1.04-1.6). CONCLUSIONS: This
      study reports for the first time a high prevalence of osteoporotic vertebral
      fractures in an unselected acromegalic male population generally considered at
      low risk of osteoporosis, suggesting that complicated osteoporosis is an
      important comorbidity of acromegaly.

PMID- 18827005
TI  - Vitamin D receptor genotype in hypophosphatemic rickets as a predictor of growth
      and response to treatment.
AB  - CONTEXT: Treatment of X-linked hypophosphatemic rickets improves bone
      mineralization and bone deformities, but its effect on skeletal growth is highly
      variable. OBJECTIVE: Genetic variants in the promoter region of the vitamin D
      receptor (VDR) gene may explain the response to treatment because this receptor
      mediates vitamin D action. DESIGN: We studied the VDR promoter haplotype
      structure in a large cohort of 91 patients with hypophosphatemic rickets
      including 62 patients receiving 1alpha-hydroxyvitamin D3 derivatives and
      phosphates from early childhood on. RESULTS: Treatment improved bone deformities
      and final height, but 39% of treated patients still had short stature at the end
      of growth (-2 sd score or below). Height was closely associated with VDR promoter
      Hap1 genotype. Hap1(-) patients (35% of the cohort) had severe growth defects.
      This disadvantageous association of Hap1(-) status with height was visible before
      treatment, under treatment, and on to adulthood. Gender and age at initiation of
      treatment could not account for the Hap1 effect. No association with growth was
      found with a polymorphism of the PTH receptor gene otherwise found to be
      associated with adult height. Compared with Hap1(+) patients, those who were
      Hap1(-) had a higher urinary calcium response to 1alpha-hydroxyvitamin D3 and had
      significantly lower circulating FGF23 levels (C-terminal assay), taking into
      account their phosphate and 1alpha-hydroxyvitamin D3 intakes. CONCLUSIONS: The
      present work identifies the VDR promoter genotype as a key predictor of growth
      under treatment with 1alpha-hydroxyvitamin D3 derivatives in patients with
      hypophosphatemic rickets, including those with established PHEX alterations. The
      VDR promoter genotype appears to provide valuable information for adjusting
      treatment and for deciding upon the utility of early GH therapy.

PMID- 18827006
TI  - SHP-2 is a novel target of Abl kinases during cell proliferation.
AB  - Previously, we showed that Abl family tyrosine kinases are activated by growth
      factors, and Abl is required for transition from G1 to S phase during PDGF
      mediated proliferation. Here, we show that the SHP-2 tyrosine phosphatase, which
      acts to promote proliferation in response to cytokines and growth factors, is a
      novel substrate of endogenous Abl kinases during growth factor-mediated cellular
      proliferation. Using a pharmacological inhibitor and RNAi, we show that
      endogenous Abl kinases phosphorylate SHP-2 on Y580, and induce sustained
      activation of ERK kinases in response to growth factor stimulation in
      fibroblasts. Consistent with these data, SHP-2 is required for Abl-dependent PDGF
      mediated proliferation since expression of an activated form of SHP-2 rescues the
      ability of Abl-Arg null fibroblasts to transit from G1 to S phase, whereas
      inhibition of SHP-2 signaling reduces the ability of Abl kinases to rescue the
      proliferation defect. Abl kinases also indirectly mediate phosphorylation of SHP
      2 on Y63 and Y279, which are frequent sites of germline mutation in two cancer
      susceptibility syndromes. Significantly, we demonstrate that phosphorylation of
      SHP-2 on Y279 downregulates growth factor-induced sustained ERK activation and
      proliferation, supporting a role for Abl kinases not only in potentiating growth
      factor-mediated SHP-2 signaling, but also in negative-feedback regulation.

PMID- 18827007
TI  - Human kidney anion exchanger 1 localisation in MDCK cells is controlled by the
      phosphorylation status of two critical tyrosines.
AB  - An important question in renal physiology is how the alpha-intercalated cells of
      the kidney regulate the distribution of the basolateral kidney anion exchanger 1
      (kAE1) according to systemic acid-base status. Previous work using a MDCKI model
      system demonstrated that kAE1 basolateral targeting requires an N-terminal
      determinant and a critical C-terminal tyrosine (Y904). Here, we show that the N
      terminal determinant is residue Y359, because a Y359A substitution mutant was
      mistargeted to the apical membrane. Further determinants might exist because a
      range of N-terminal kAE1 truncations that contained Y359 were incorrectly
      targeted to the TGN. Y359 and Y904 in kAE1 are phosphorylated upon pervanadate
      treatment and this phosphorylation is sensitive to specific Src kinase family
      inhibitors. We tested a range of stimuli on this model system and only the
      application of high nonphysiological concentrations of extracellular bicarbonate,
      and to a lesser extent hypertonicity or hyperosmolarity, induced tyrosine
      phosphorylation of kAE1. Treatment with pervanadate caused internalisation of
      kAE1 from the plasma membrane, but treatment with high concentrations of
      bicarbonate did not, because of the hypertonicity of the solution. We propose
      that alpha-intercalated cells control the distribution of kAE1 by reversible
      phosphorylation of tyrosine residues Y359 and Y904.

PMID- 18827008
TI  - The protein phosphatase PP2A-B' subunit Widerborst is a negative regulator of
      cytoplasmic activated Akt and lipid metabolism in Drosophila.
AB  - Inappropriate regulation of the PI3-kinase/PTEN/Akt kinase-signalling cassette, a
      key downstream target of insulin/insulin-like growth factor signalling (IIS), is
      associated with several major human diseases such as diabetes, obesity and
      cancer. In Drosophila, studies have recently revealed that different subcellular
      pools of activated, phosphorylated Akt can modulate different IIS-dependent
      processes. For example, a specific pool of activated Akt within the cytoplasm
      alters aspects of lipid metabolism, a process that is misregulated in both
      obesity and diabetes. However, it remains unclear how this pool is regulated.
      Here we show that the protein phosphatase PP2A-B' regulatory subunit Widerborst
      (Wdb), which coimmunoprecipitates with Akt in vivo, selectively modulates levels
      of activated Akt in the cytoplasm. It alters lipid droplet size and expression of
      the lipid storage perilipin-like protein LSD2 in the Drosophila ovary, but not in
      epithelial cells of the eye imaginal discs. We conclude that isoforms of PP2A-B'
      can act as subcellular-compartment-specific regulators of PI3-kinase/PTEN/Akt
      kinase signalling and IIS, potentially providing new targets for modulating
      individual subcellular pools of activated Akt in insulin-linked disease.

PMID- 18827009
TI  - Mitochondrial dysfunction and HIF1alpha stabilization in inflammation.
AB  - Activation of murine-derived J774.A1 macrophages with interferon gamma and
      lipopolysaccharide leads to a progressive mitochondrial defect characterized by
      inhibition of oxygen consumption and a decrease in the generation of ATP by
      oxidative phosphorylation. These changes are dependent on the generation of
      nitric oxide (NO) by an inducible NO synthase that becomes a significant consumer
      of oxygen. Furthermore, in these activated cells there is a biphasic
      stabilization of the hypoxia-inducible factor HIF1alpha, the second phase of
      which is also dependent on the presence of NO. The mitochondrial defect and
      stabilization of HIF1alpha synergize to activate glycolysis, which, at its
      maximum, generates quantities of ATP greater than those produced by non-activated
      cells. Nevertheless, the amount of ATP generated is not sufficient to fulfil the
      energy requirements of the activated cells, probably leading to a progressive
      energy deficit with the consequent inhibition of cell proliferation and death.

PMID- 18827010
TI  - CED-9 and mitochondrial homeostasis in C. elegans muscle.
AB  - Mitochondrial homeostasis reflects a dynamic balance between membrane fission and
      fusion events thought essential for mitochondrial function. We report here that
      altered expression of the C. elegans BCL2 homolog CED-9 affects both
      mitochondrial fission and fusion. Although striated muscle cells lacking CED-9
      have no alteration in mitochondrial size or ultrastructure, these cells appear
      more sensitive to mitochondrial fragmentation. By contrast, increased CED-9
      expression in these cells produces highly interconnected mitochondria. This
      mitochondrial phenotype is partially suppressed by increased expression of the
      dynamin-related GTPase DRP-1, with suppression dependent on the BH3 binding
      pocket of CED-9. This suppression suggests that CED-9 directly regulates DRP-1, a
      model supported by our finding that CED-9 activates the GTPase activity of human
      DRP1. Thus, CED-9 is capable of regulating the mitochondrial fission-fusion cycle
      but is not essential for either fission or fusion.

PMID- 18827011
TI  - Murine CENPF interacts with syntaxin 4 in the regulation of vesicular transport.
AB  - Syntaxin 4 is a component of the SNARE complex that regulates membrane docking
      and fusion. Using a yeast two-hybrid screen, we identify a novel interaction
      between syntaxin 4 and cytoplasmic murine CENPF, a protein previously
      demonstrated to associate with the microtubule network and SNAP-25. The binding
      domain for syntaxin 4 in CENPF was defined by yeast two-hybrid assay and co
      immunoprecipitation. Confocal analyses in cell culture reveal a high degree of
      colocalization between endogenously expressed proteins in interphase cells.
      Additionally, the endogenous SNARE proteins can be isolated as a complex with
      CENPF in immunoprecipitation experiments. Further analyses demonstrate that
      murine CENPF and syntaxin 4 colocalize with components of plasma membrane
      recycling: SNAP-25 and VAMP2. Depletion of endogenous CENPF disrupts GLUT4
      trafficking whereas expression of a dominant-negative form of CENPF inhibits cell
      coupling. Taken together, these studies demonstrate that CENPF provides a direct
      link between proteins of the SNARE system and the microtubule network and
      indicate a diverse role for murine CENPF in vesicular transport.

PMID- 18827012
TI  - The ENTH and C-terminal domains of Dictyostelium epsin cooperate to regulate the
      dynamic interaction with clathrin-coated pits.
AB  - Epsin contains a phospholipid-binding ENTH domain coupled to C-terminal domain
      motifs that bind coated pit proteins. We examined how these domains interact to
      influence epsin function and localization in Dictyostelium. Although not required
      for global clathrin function, epsin was essential for constructing oval spores
      during development. Within the epsin protein, we found that features important
      for essential function were distinct from features targeting epsin to clathrin
      coated pits. On its own, the phospholipid-binding ENTH domain could rescue the
      epsin-null phenotype. Although necessary and sufficient for function, the
      isolated ENTH domain was not targeted within clathrin-coated pits. The C-terminal
      domain containing the coated-pit motif was also insufficient, highlighting a
      requirement for both domains for targeting to coated pits. Replacement of the
      ENTH domain by an alternative membrane-binding domain resulted in epsin that
      sequestered clathrin and AP2 and ablated clathrin function, supporting a
      modulatory role for the ENTH domain. Within the ENTH domain, residues important
      for PtdIns(4,5)P2 binding were essential for both epsin localization and
      function, whereas residue T107 was essential for function but not coated pit
      localization. Our results support a model where the ENTH domain coordinates with
      the clathrin-binding C-terminal domain to allow a dynamic interaction of epsin
      with coated pits.

PMID- 18827013
TI  - Sorting of EGF and transferrin at the plasma membrane and by cargo-specific
      signaling to EEA1-enriched endosomes.
AB  - The biological function of receptors is determined by their appropriate
      trafficking through the endosomal pathway. Following internalization, the
      transferrin (Tf) receptor quantitatively recycles to the plasma membrane, whereas
      the epidermal growth factor (EGF) receptor undergoes degradation. To determine
      how Tf and EGF engage these two different pathways we imaged their binding and
      early endocytic pathway in live cells using total internal reflection
      fluorescence microscopy (TIRF-M). We find that EGF and Tf bind to distinct plasma
      membrane regions and are incorporated into different endocytic vesicles. After
      internalization, both EGF-enriched and Tf-enriched vesicles interact with
      endosomes containing early endosome antigen 1 (EEA1). EGF is incorporated and
      retained in these endosomes, while Tf-containing vesicles rapidly dissociate and
      move to a juxtanuclear compartment. Endocytic vesicles carrying EGF recruit more
      Rab5 GTPase than those carrying Tf, which, by strengthening their association
      with EEA1-enriched endosomes, may provide a mechanism for the observed cargo
      specific sorting. These results reveal pre-endocytic sorting of Tf and EGF, a
      specialized role for EEA1-enriched endosomes in EGF trafficking, and a potential
      mechanism for cargo-specified sorting of endocytic vesicles by these endosomes.

PMID- 18827014
TI  - G-actin regulates rapid induction of actin nucleation by mDia1 to restore
      cellular actin polymers.
AB  - mDia1 belongs to the formin family of proteins that share FH1 and FH2 domains.
      Although formins play a critical role in the formation of many actin-based
      cellular structures, the physiological regulation of formin-mediated actin
      assembly within the cell is still unknown. Here we show that cells possess an
      acute actin polymer restoration mechanism involving mDia1. By using single
      molecule live-cell imaging, we found that several treatments including low-dose G
      actin-sequestering drugs and unpolymerizable actin mutants activate mDia1 to
      initiate fast directional movement. The FH2 region, the core domain for actin
      nucleation, is sufficient to respond to latrunculin B (LatB) to increase its
      actin nucleation frequency. Simulation analysis revealed an unexpected
      paradoxical effect of LatB that leads to a several fold increase in free G-actin
      along with an increase in total G-actin. These results indicate that in cells,
      the actin nucleation frequency of mDia1 is enhanced not only by Rho, but also
      strongly through increased catalytic efficiency of the FH2 domain. Consistently,
      frequent actin nucleation by mDia1 was found around sites of vigorous actin
      disassembly. Another major actin nucleator, the Arp2/3 complex, was not affected
      by the G-actin increase induced by LatB. Taken together, we propose that
      transient accumulation of G-actin works as a cue to promote mDia1-catalyzed actin
      nucleation to execute rapid reassembly of actin filaments.

PMID- 18827015
TI  - TorsinA binds the KASH domain of nesprins and participates in linkage between
      nuclear envelope and cytoskeleton.
AB  - A specific mutation (DeltaE) in torsinA underlies most cases of the dominantly
      inherited movement disorder, early-onset torsion dystonia (DYT1). TorsinA, a
      member of the AAA+ ATPase superfamily, is located within the lumen of the nuclear
      envelope (NE) and endoplasmic reticulum (ER). We investigated an association
      between torsinA and nesprin-3, which spans the outer nuclear membrane (ONM) of
      the NE and links it to vimentin via plectin in fibroblasts. Mouse nesprin-3alpha
      co-immunoprecipitated with torsinA and this involved the C-terminal region of
      torsinA and the KASH domain of nesprin-3alpha. This association with human
      nesprin-3 appeared to be stronger for torsinADeltaE than for torsinA. TorsinA
      also associated with the KASH domains of nesprin-1 and -2 (SYNE1 and 2), which
      link to actin. In the absence of torsinA, in knockout mouse embryonic fibroblasts
      (MEFs), nesprin-3alpha was localized predominantly in the ER. Enrichment of
      yellow fluorescent protein (YFP)-nesprin-3 in the ER was also seen in the
      fibroblasts of DYT1 patients, with formation of YFP-positive globular structures
      enriched in torsinA, vimentin and actin. TorsinA-null MEFs had normal NE
      structure, but nuclear polarization and cell migration were delayed in a wound
      healing assay, as compared with wild-type MEFs. These studies support a role for
      torsinA in dynamic interactions between the KASH domains of nesprins and their
      protein partners in the lumen of the NE, with torsinA influencing the
      localization of nesprins and associated cytoskeletal elements and affecting their
      role in nuclear and cell movement.

PMID- 18827016
TI  - Loss of protein kinase Cepsilon results in impaired cutaneous wound closure and
      myofibroblast function.
AB  - Cutaneous wound repair requires the de novo induction of a specialized form of
      fibroblast, the alpha-smooth muscle actin (alpha-SMA)-expressing myofibroblast,
      which migrates into the wound where it adheres to and contracts extracellular
      matrix (ECM), resulting in wound closure. Persistence of the myofibroblast
      results in scarring and fibrotic disease. In this report, we show that, compared
      with wild-type littermates, PKCepsilon-/- mice display delayed impaired cutaneous
      wound closure and a reduction in myofibroblasts. Moreover, both in the presence
      and absence of TGFbeta, dermal fibroblasts from PKCepsilon-/- mice cultured on
      fibronectin show impaired abilities to form ;supermature' focal adhesions and
      alpha-SMA stress fibers, and reduced pro-fibrotic gene expression. Smad3
      phosphorylation in response to TGFbeta1 was impaired in PKCepsilon-/-
      fibroblasts. PKCepsilon-/- fibroblasts show reduced FAK and Rac activation, and
      adhesive, contractile and migratory abilities. Overexpressing constitutively
      active Rac1 rescues the defective FAK phosphorylation, cell migration, adhesion
      and stress fiber formation of these PKCepsilon-/- fibroblasts, indicating that
      Rac1 operates downstream of PKCepsilon, yet upstream of FAK. These results
      suggest that loss of PKCepsilon severely impairs myofibroblast formation and
      function, and that targeting PKCepsilon may be beneficial in selectively
      modulating wound healing and fibrotic responses in vivo.

PMID- 18827017
TI  - Reduced tumorigenesis in mouse mammary cancer cells following inhibition of Pea3-
      or Erm-dependent transcription.
AB  - Pea3 and Erm are transcription factors expressed in normal developing branching
      organs such as the mammary gland. Deregulation of their expression is generally
      associated with tumorigenesis and particularly breast cancer. By using RNA
      interference (RNAi) to downregulate the expression of Pea3 and/or Erm in a
      mammary cancer cell line, we present evidence for a role of these factors in
      proliferation, migration and invasion capacity of cancer cells. We have used
      different small interfering RNAs (siRNAs) targeting pea3 and erm transcripts in
      transiently or stably transfected cells, and assessed the physiological behavior
      of these cells in in vitro assays. We also identified an in vivo alteration of
      tumor progression after injection of cells that overexpress pea3 and/or erm short
      hairpin RNAs (shRNAs) in immunodeficient mice. Using transcriptome profiling in
      Pea3- or Erm-targeted cells, two largely independent gene expression programs
      were identified on the basis of their shared phenotypic modifications. A
      statistically highly significant part of both sets of target genes had previously
      been already associated with the cellular signaling pathways of the
      ;proliferation, migration, invasion' class. These data provide the first
      evidence, by using endogenous knockdown, for pivotal and complementary roles of
      Pea3 and Erm transcription factors in events crucial to mammary tumorigenesis,
      and identify sets of downstream target genes whose expression during
      tumorigenesis is regulated by these transcription factors.

PMID- 18827018
TI  - Myofibroblast communication is controlled by intercellular mechanical coupling.
AB  - Neoformation of intercellular adherens junctions accompanies the differentiation
      of fibroblasts into contractile myofibroblasts, a key event during development of
      fibrosis and in wound healing. We have previously shown that intercellular
      mechanical coupling of stress fibres via adherens junctions improves contraction
      of collagen gels by myofibroblasts. By assessing spontaneous intracellular Ca2+
      oscillations, we here test whether adherens junctions mechanically coordinate
      myofibroblast activities. Periodic Ca2+ oscillations are synchronised between
      physically contacting myofibroblasts and become desynchronised upon dissociation
      of adherens junctions with function-blocking peptides. Similar uncoupling is
      obtained by inhibiting myofibroblast contraction using myosin inhibitors and by
      blocking mechanosensitive ion channels using Gd3+ and GSMTx4. By contrast, gap
      junction uncouplers do not affect myofibroblast coordination. We propose the
      following model of mechanical coupling for myofibroblasts: individual cell
      contraction is transmitted via adherens junctions and leads to the opening of
      mechanosensitive ion channels in adjacent cells. The resulting Ca2+ influx
      induces a contraction that can feed back on the first cell and/or stimulate other
      contacting cells. This mechanism could improve the remodelling of cell-dense
      tissue by coordinating the activity of myofibroblasts.

PMID- 18827019
TI  - Higher muscle protein synthesis in women than men across the lifespan, and
      failure of androgen administration to amend age-related decrements.
AB  - We investigated age and sex effects and determined whether androgen replacement
      in elderly individuals (> or = 60 yr) could augment protein synthesis. Thirty
      young men and 32 young women (18-31 yr) were studied once, whereas 87 elderly men
      were studied before and after 1 yr of treatment with 5 mg/day testosterone (T),
      75 mg/day dehydroepiandrosterone (DHEA), or placebo (P); and 57 elderly women
      were studied before and after 1 yr of treatment with 50 mg/day DHEA or P.
      [(15)N]Phenylalanine and [(2)H(4)]tyrosine tracers were infused, with
      measurements in plasma and vastus lateralis muscle. Whole-body protein synthesis
      per fat-free mass and muscle protein fractional synthesis rate (FSR) were lower
      in elderly than in young individuals (P<0.001), not significantly affected by
      hormone treatments, and higher in women than in men (P<0.0001), with no sex x age
      interaction. In regression analyses, peak O2 consumption (VO2peak), resting
      energy expenditure (REE), and sex were independently associated with muscle FSR,
      as were VO2peak, REE, and interactions of sex with insulin-like growth factor-II
      and insulin for whole-body protein synthesis. Women maintain higher protein
      synthesis than men across the lifespan as rates decline in both sexes, and
      neither full replacement of DHEA (in elderly men and women) nor partial
      replacement of bioavailable T (in elderly men) is able to amend the age-related
      declines.

PMID- 18827020
TI  - A splice variant of the SLC28A3 gene encodes a novel human concentrative
      nucleoside transporter-3 (hCNT3) protein localized in the endoplasmic reticulum.
AB  - Nucleoside transporters are plasma membrane proteins essential for nucleoside
      salvage. Among them, human concentrative nucleoside transporter 3 (hCNT3,
      SLC28A3) plays an essential role in this process because of its broader substrate
      selectivity and higher concentrative ability than the other members of the SLC28
      protein family, hCNT1 and hCNT2. The aim of this study was to characterize an
      isoform of hCNT3, encoded by an alternatively spliced SLC28A3-related mRNA, the
      first identified for a CNT protein. This variant, named hCNT3ins, is the result
      of the insertion of 176 bp corresponding to an intron located between exons 2 and
      3 of the gene. This insertion results in a shift of the reading frame, yielding a
      protein lacking 69 residues of the N terminus. hCNT3 and hCNT3ins mRNAs are
      simultaneously expressed both in normal and transformed cells and are
      differentially regulated by activation and differentiation. Because of the N
      terminal deletion, hCNT3ins is retained in the endoplasmic reticulum, where it
      shows a typical hCNT3-related activity. hCNT3ins exhibits a shorter half-life
      than its plasma membrane counterpart, being degraded via a proteasome-dependent
      pathway. We suggest that this novel hCNT3 isoform would be involved in the
      salvage of intracellular nucleosides from the lumen of the endoplasmic reticulum
      to the cytoplasm.

PMID- 18827021
TI  - High-fat diet before and during pregnancy causes marked up-regulation of
      placental nutrient transport and fetal overgrowth in C57/BL6 mice.
AB  - Maternal overweight and obesity in pregnancy often result in fetal overgrowth,
      which increases the risk for the baby to develop metabolic syndrome later in
      life. However, the mechanisms underlying fetal overgrowth are not established. We
      developed a mouse model and hypothesized that a maternal high-fat (HF) diet
      causes up-regulation of placental nutrient transport, resulting in fetal
      overgrowth. C57BL/6J female mice were fed a control (11% energy from fat) or HF
      (32% energy from fat) diet for 8 wk before mating and throughout gestation and
      were studied at embryonic day 18.5. The HF diet increased maternal adiposity, as
      assessed by fat pad weight, and circulating maternal leptin, decreased serum
      adiponectin concentrations, and caused a marked increase in fetal growth (+43%).
      The HF diet also increased transplacental transport of glucose (5-fold) and
      neutral amino acids (10-fold) in vivo. In microvillous plasma membranes (MVMs)
      isolated from placentas of HF-fed animals, protein expression of glucose
      transporter 1 (GLUT1) was increased 5-fold, and protein expression of sodium
      coupled neutral amino acid transporter (SNAT) 2 was elevated 9-fold. In contrast,
      MVM protein expression of GLUT 3 or SNAT4 was unaltered. These data suggest that
      up-regulation of specific placental nutrient transporter isoforms constitute a
      mechanism linking maternal high-fat diet and obesity to fetal overgrowth.

PMID- 18827022
TI  - The IkappaB kinases IKKalpha and IKKbeta are necessary and sufficient for
      skeletal muscle atrophy.
AB  - Nuclear factor-kappaB (NF-kappaB) signaling is necessary for many types of muscle
      atrophy, yet only some of the required components have been identified. Gene
      transfer of a dominant negative (d.n.) IKKbeta into rat soleus muscles showed
      complete inhibition of 7-day disuse-induced activation of a kappaB reporter gene,
      while overexpression of wild-type (w.t.) IKKbeta did not. Overexpression of a
      d.n. IKKbeta-EGFP fusion protein showed that atrophy was inhibited by 50%,
      indicating that IKKbeta is required for the atrophy process. Overexpression of
      constitutively active (c.a.) IKKbeta-EGFP showed a marked increase in NF-kappaB
      activity and a decrease in fiber size of weight-bearing soleus muscles, while
      muscles overexpressing w.t. IKKbeta-HA had no effect. The same results were found
      for IKKalpha; overexpression of a d.n. form of the protein decreased unloading
      induced NF-kappaB activation and inhibited atrophy by 50%, while overexpression
      of the w.t. protein had no effect. Overexpression of a c.a. IKKalpha-EGFP fusion
      protein showed that IKKalpha was sufficient to activate NF-kappaB activity and
      induce fiber atrophy in muscle. Overexpression of d.n. IKKbeta plus d.n. IKKalpha
      showed an additive effect on the inhibition of disuse atrophy (70%), suggesting
      that both kinases of the IKK complex are required for muscle atrophy. These data
      show that both IKKalpha and IKKbeta are necessary and sufficient for
      physiological muscle atrophy.

PMID- 18827023
TI  - Differential roles of PDGFR-alpha and PDGFR-beta in angiogenesis and vessel
      stability.
AB  - Preclinical and clinical evaluations of individual proangiogenic/arteriogenic
      factors for the treatment of ischemic myocardium and skeletal muscle have
      produced unfulfilled promises. The establishment of functional and stable
      arterial vascular networks may require combinations of different angiogenic and
      arteriogenic factors. Using in vivo angiogenesis and ischemic hind-limb animal
      models, we have compared the angiogenic and therapeutic activities of fibroblast
      growth factor 2 (FGF-2) in combinations with PDGF-AA and PDGF-AB, two members of
      the platelet-derived growth factor (PDGF) family, with distinct receptor binding
      patterns. We show that both PDGF-AA/FGF-2 and PDGF-AB/FGF-2 in combinations
      synergistically induce angiogenesis in the mouse cornea. FGF-2 up-regulates PDGFR
      alpha and -beta expression levels in the newly formed blood vessels.
      Interestingly, PDGF-AB/FGF-2, but not PDGF-AA/FGF-2, is able to stabilize the
      newly formed vasculature by recruiting pericytes, and an anti-PDGFR-beta
      neutralizing antibody significantly blocks PDGF-AB/FGF-2-induced vessel
      stability. These findings demonstrate that PDGFR-beta receptor is essential for
      vascular stability. Similarly, PDGF-AB/FGF-2 significantly induces stable
      collateral growth in the rat ischemic hind limb. The high number of collaterals
      induced by PDGF-AB/FGF-2 leads to dramatic improvement of the paw's skin
      perfusion. Immunohistochemical analysis of the treated skeletal muscles confirms
      that a combination of PDGF-AB and FGF-2 significantly induces arteriogenesis in
      the ischemic tissue. A combination of PDGF-AB and FGF-2 would be optimal
      proangiogenic agents for the treatment of ischemic diseases.

PMID- 18827024
TI  - Erythropoietin administration after myocardial infarction in mice attenuates
      ischemic cardiomyopathy associated with enhanced homing of bone marrow-derived
      progenitor cells via the CXCR-4/SDF-1 axis.
AB  - Mobilization of bone marrow-derived stem cells (BMCs) was shown to have
      protective effects after myocardial infarction (MI). However, the classical
      mobilizing agent, granulocyte-colony stimulating factor (G-CSF) relapsed after
      revealing an impaired homing capacity. In the search for superior cytokines,
      erythropoietin (EPO) appears to be a promising agent. Therefore, we analyzed in a
      murine model of surgically induced MI the influence of EPO treatment on survival
      and functional parameters as well as BMC mobilization, homing, and effect on
      resident cardiac stem cells (CSCs). Human EPO was injected intraperitoneally
      after ligation of the left anterior descendens (LAD) for 3 days with a total dose
      of 5000 IU/kg 6 and 30 days after MI, and pressure volume relationships were
      investigated in vivo. Cardiac tissues were analyzed by histology. To show the
      effect on BMCs and CSCs, FACS analyses were performed. Homing factors were
      analyzed by quantitative reverse transcription-polymerase chain reaction (qRT
      PCR) and ELISA. EPO-treated animals showed a significant improvement of survival
      post-MI (62 vs. 36%). At days 6 and 30, all hemodynamic parameters associated
      with attenuated remodeling, enhanced neovascularization, and diminished apoptotic
      cells in the peri-infarct area were improved. BMC subpopulations (CD31(+), c
      kit(+), and Sca-1(+) cells) were mobilized, and homing of Sca-1(+) and CXCR4(+)
      BMCs toward an SDF-1 gradient into the ischemic myocardium was enhanced. However,
      there was no beneficial effect on CSCs. We have shown that EPO application after
      MI shows cardioprotective effects. This may be explained by mobilization of BMCs,
      which are homing via the CXCR-4/SDF-1 axis. However, EPO has no beneficial
      effects on resident CSCs. Therefore, new treatment regimes using EPO together
      with other agents may combine complementary beneficial effects preventing
      ischemic cardiomyopathy.

PMID- 18827025
TI  - Isolation and functional characterization of a stable complex between
      photoactivated rhodopsin and the G protein, transducin.
AB  - Transitory binding between photoactivated rhodopsin (Rho* or Meta II) and the G
      protein transducin (Gt-GDP) is the first step in the visual signaling cascade.
      Light causes photoisomerization of the 11-cis-retinylidene chromophore in
      rhodopsin (Rho) to all-trans-retinylidene, which induces conformational changes
      that allow Gt-GDP to dock onto the Rho* surface. GDP then dissociates from Gt,
      leaving a transient nucleotide-empty Rho*-Gt(e) complex before GTP becomes bound,
      and Gt-GTP then dissociates from Rho*. Further biochemical advances are required
      before structural studies of the various Rho*-Gt complexes can be initiated.
      Here, we describe the isolation of n-dodecyl-beta-maltoside solubilized, stable,
      functionally active, Rho*-Gt(e), Rho(e)*-Gt(e), and 9-cis-retinal/11-cis-retinal
      regenerated Rho-Gt(e) complexes by sucrose gradient centrifugation. In these
      complexes, Rho* spectrally remained in its Meta II state, and Gt(e) retained its
      ability to interact with GTPgammaS. Removal of all-trans-retinylidene from Rho*
      Gt(e) had no effect on the stability of the Rho(e)*-Gt(e) complex. Moreover,
      opsin in the Rho(e)*-Gt(e) complex with an empty nucleotide-binding pocket in Gt
      and an empty retinoid-binding pocket in Rho was regenerated up to 75% without
      complex dissociation. These results indicate that once Rho* couples with Gt, the
      chromophore plays a minor role in stabilizing this complex. Moreover, in
      complexes regenerated with 9-cis-retinal/11-cis-retinal, Rho retains a
      conformation similar to Rho* that is stabilized by Gt(e) apo-protein.

PMID- 18827026
TI  - Bone marrow-derived cell regulation of skeletal muscle regeneration.
AB  - Limb regeneration requires the coordination of multiple stem cell populations to
      recapitulate the process of tissue formation. Therefore, bone marrow (BM) 
      derived cell regulation of skeletal muscle regeneration was examined in mice
      lacking the CC chemokine receptor 2 (CCR2). Myofiber size, numbers of myogenic
      progenitor cells (MPCs), and recruitment of BM-derived cells and macrophages were
      assessed after cardiotoxin-induced injury of chimeric mice produced by
      transplanting BM from wild-type (WT) or CCR2(-/-) mice into irradiated WT or
      CCR2(-/-) host mice. Regardless of the host genotype, muscle regeneration and
      recruitment of BM-derived cells and macrophages were similar in mice replenished
      with WT BM, whereas BM-derived cells and macrophage accumulation were decreased
      and muscle regeneration was impaired in all animals receiving CCR2(-/-) BM.
      Furthermore, numbers of MPCs (CD34(+)/Sca-1(-)/CD45(-) cells) were significantly
      increased in mice receiving CCR2(-/-) BM despite the decreased size of
      regenerated myofibers. Thus, the expression of CCR2 on BM-derived cells regulated
      macrophage recruitment into injured muscle, numbers of MPC, and the extent of
      regenerated myofiber size, all of which were independent of CCR2 expression on
      host-derived cells. Future studies in regenerative medicine must include
      consideration of the role of BM-derived cells, possibly macrophages, in CCR2
      dependent events that regulate effective skeletal muscle regeneration.

PMID- 18827027
TI  - Sole copy of Z2-type human cytidine deaminase APOBEC3H has inhibitory activity
      against retrotransposons and HIV-1.
AB  - Human cytidine deaminase apolipoprotein B mRNA-editing catalytic polypeptide-like
      3 (APOBEC3) proteins have been classified as either Z1- or Z2-type cytidine
      deaminases on the basis of phylogenetic analysis of their catalytic domains.
      Despite the identification of a number of Z1-type domain-containing cytidine
      deaminases, only one copy of Z2-type cytidine deaminase has been detected in each
      of the mammalian species evaluated thus far. Z1-type human APOBEC3 proteins are
      known to exhibit broad activities against diverse retroelements. However, the
      potential role of the only human Z2-type cytidine deaminase, APOBEC3H (A3H), in
      the restriction of retroelements has not yet been fully characterized. Here, we
      demonstrate that human A3H is a potent inhibitor of non-LTR LINE-1 transposition.
      Interestingly, it was also as efficient as A3G in inhibiting Alu
      retrotransposition, despite its poor association with Alu RNA. We have further
      demonstrated, for the first time, that human APOBEC3DE is also a potent inhibitor
      of Alu retrotransposition. Variants of A3H have divergent antiviral activities
      against HIV-1-Vif-deficient viruses. Unlike the anti-HIV-1 cytidine deaminases
      A3G and A3F, A3H is moderately regulated by interferons. These observations
      suggest that human Z2-type cytidine deaminase A3H variants have varying intrinsic
      abilities to restrict retroelements and that various APOBEC3 proteins may have
      evolved distinct inhibitory mechanisms against retroelements.

PMID- 18827028
TI  - Science as oath and testimony: Joshua Lederberg (1925-2008).

PMID- 18827030
TI  - Comment on "Production of multivalent protein binders using a self-trimerization
      collagen-like peptide scaffold".

PMID- 18827031
TI  - Vascularized tissue-engineered chambers promote survival and function of
      transplanted islets and improve glycemic control.

PMID- 18827032
TI  - Normalization of echocardiographically derived paediatric cardiac dimensions to
      body surface area: time for a standardized approach.

PMID- 18827033
TI  - Left ventricular size determines tissue Doppler-derived longitudinal strain and
      strain rate.
AB  - AIMS: Tissue Doppler-derived indices of strain (epsilon) and strain rate (SR)
      have been developed to assess regional cardiac function. However, the effect of
      left ventricular (LV) size on epsilon and SR has not been studied in depth. The
      aim of this study was to assess to what extent heart size influence epsilon or
      SR. METHODS AND RESULTS: In 21 anaesthetized pigs ranging from 12.5 to 70.0 kg,
      tissue Doppler-derived epsilon and SR, and haemodynamic parameters, were assessed
      during controlled heart rates and different loading conditions. dP/dt did not
      correlate to pig weight, suggesting constant contractility during growth.
      Longitudinal epsilon and SR were significantly higher in smaller compared with
      larger hearts. The hyperbolic correlation between pigs weight and epsilon and SR
      was r(2)=0.621 and 0.372, respectively, both P<0.0001. Afterload elevation
      induced a reduction in longitudinal epsilon (from -24.2+/-3.2 to -12.1+/-5.5%,
      P=0.001) and SR (from -2.3+/-0.8 to -1.3+/-2.4 s(-1), P=0.034), whereas
      increasing preload increased epsilon (from -26.4+/-10.3 to -38.1+/-14.3%,
      P=0.006) and SR (from -2.3+/-0.9 to -4.22+/-1.8 s(-1), P=0.002). CONCLUSION:
      Longitudinal epsilon and SR decrease with increasing LV dimensions in spite of an
      unaltered contractility. These results show and confirm that heart size
      influences epsilon and SR, which are highly load-dependent parameters.

PMID- 18827034
TI  - Prevalence and distribution of plasmid-mediated quinolone resistance genes in
      clinical isolates of Escherichia coli lacking extended-spectrum beta-lactamases.
AB  - OBJECTIVES: The aac(6')-Ib-cr gene has been described in plasmids from CTX-M-15
      producing Escherichia coli in the worldwide ST131 lineage, but has not been
      systematically sought in other quinolone-resistant strains in the UK. A rise in
      quinolone resistance in bacteraemia isolates in the UK preceded the increased
      prevalence of CTX-M-producing strains. This study aimed to describe the presence
      of plasmid-encoded quinolone resistance genes in historical and current strains
      of E. coli not producing extended-spectrum beta-lactamases (ESBLs). METHODS:
      Ciprofloxacin-resistant, non-ESBL-producing E. coli isolates included nationally
      distributed isolates from the BSAC UK bacteraemia surveillance programme between
      2001 and 2005, urinary isolates from a regional project in 2000 and local strains
      in 2006. The aac(6')-Ib-cr gene was detected using PCR followed by restriction
      fragment length polymorphism analysis. Multiplex PCR was used to detect qnr
      genes. Isolates with aac(6')-Ib-cr were assessed for aminoglycoside
      susceptibilities and were serotyped. RESULTS: The prevalence of the aac(6')-Ib-cr
      gene was 3% and 9% in current local urinary and historic national bacteraemia
      quinolone-resistant non-ESBL-producing E. coli, respectively. Of 521 regional
      urinary E. coli isolates from 2000, 14 were norfloxacin-resistant, none of which
      carried the aac(6')-Ib-cr gene. National positive bacteraemia isolates from
      2001/2 were type O102-ST405 and, in 2004/5, types O1-ST645 and O25-ST131.
      Positive local urinary isolates from 2006 included serotypes O1 and O25.
      CONCLUSIONS: In the UK, aac(6')-Ib-cr occurs in E. coli in the absence of CTX-M
      15, but with a restricted serotype distribution. Its presence in widespread
      bacteraemia isolates of a single type from 2001 to 2002, prior to the spread of
      CTX-M-15 in Britain, might suggest a lineage from which plasmid recombination
      occurred in man or other species.

PMID- 18827035
TI  - How does increasingly plainer cigarette packaging influence adult smokers'
      perceptions about brand image? An experimental study.
AB  - BACKGROUND: Cigarette packaging is a key marketing strategy for promoting brand
      image. Plain packaging has been proposed to limit brand image, but tobacco
      companies would resist removal of branding design elements. METHOD: A 3 (brand
      types) x 4 (degree of plain packaging) between-subject experimental design was
      used, using an internet online method, to expose 813 adult Australian smokers to
      one randomly selected cigarette pack, after which respondents completed ratings
      of the pack. RESULTS: Compared with current cigarette packs with full branding,
      cigarette packs that displayed progressively fewer branding design elements were
      perceived increasingly unfavourably in terms of smokers' appraisals of the packs,
      the smokers who might smoke such packs, and the inferred experience of smoking a
      cigarette from these packs. For example, cardboard brown packs with the number of
      enclosed cigarettes displayed on the front of the pack and featuring only the
      brand name in small standard font at the bottom of the pack face were rated as
      significantly less attractive and popular than original branded packs. Smokers of
      these plain packs were rated as significantly less trendy/stylish, less
      sociable/outgoing and less mature than smokers of the original pack. Compared
      with original packs, smokers inferred that cigarettes from these plain packs
      would be less rich in tobacco, less satisfying and of lower quality tobacco.
      CONCLUSION: Plain packaging policies that remove most brand design elements are
      likely to be most successful in removing cigarette brand image associations.

PMID- 18827036
TI  - Cigarette fires and burns in a population of New Zealand smokers.
AB  - OBJECTIVES: To identify the proportion of adult cigarette smokers who have
      experienced cigarette-caused fires and burns and to describe smoker
      characteristics associated with increased risk of cigarette-caused fires and
      burns. METHODS: Data on cigarette-caused fires and burns were collected in the
      baseline questionnaire of a randomised trial of a smoking cessation intervention
      conducted in New Zealand between March 2006 and May 2007. Participants were adult
      callers to a national smoking cessation counselling service. Lifetime prevalence
      estimates of cigarette-caused fires and burns were obtained and associations
      between smoker characteristics and risk of fires and burns examined using
      logistic regression. RESULTS: Of 1097 participants in the trial at baseline, 75
      (6.8%) reported past experience of > or =1 fires caused by cigarettes (96 fires
      reported in total) and 658 (60.0%) described at least 1 cigarette-caused burn. In
      all, 57 participants (5.2%) reported burns that required medical attention. Male
      sex and Maori ethnicity (indigenous New Zealanders, who comprise 15% of the
      national population and among whom 42% of adults are smokers) were associated
      with increased risk of cigarette-caused fires. Male sex, younger age, younger age
      of smoking initiation, being unmarried, having a partner who smoked, having a
      higher education level and an annual income of $20, 000 or more were associated
      with increased risk of cigarette burn injuries. CONCLUSIONS: The results indicate
      that cigarette-caused fires and burns are common among New Zealand smokers, are a
      source of inequality and therefore deserve greater attention from health
      advocates and policymakers.

PMID- 18827037
TI  - Welcome to Serbia: feel free to smoke.
AB  - This paper reviews tobacco use and control policies in Serbia. Tobacco
      contributes significantly to the burden of disease in Serbia, and it has one of
      the highest age standardised lung cancer incidence rates in Europe. Until
      recently there were few restrictions on smoking or tangible tobacco control
      policies. Serbia has, however, now embarked on a legislative and regulatory path
      towards greater tobacco control, but implementation and enforcement are still
      lax. Increased government interventions are needed to reduce the prevalence of
      smoking in the population.

PMID- 18827038
TI  - Signaling pathways involved in the antiproliferative effect of molecular iodine
      in normal and tumoral breast cells: evidence that 6-iodolactone mediates
      apoptotic effects.
AB  - Previous reports have documented the antiproliferative properties of I(2) and the
      arachidonic acid (AA) derivative 6-iodolactone (6-IL) in both thyroid and mammary
      glands. In this study, we characterized the cellular pathways activated by these
      molecules and their effects on cell cycle arrest and apoptosis in normal (MCF
      12F) and cancerous (MCF-7) breast cells. Low-to-moderate concentrations of I(2)
      (10-20 microM) cause G1 and G2/M phase arrest in MCF-12F and caspase-dependent
      apoptosis in MCF-7 cells. In normal cells, only high doses of I(2) (40 microM)
      induced apoptosis, and this effect was mediated by poly (ADP-ribose) polymerase-1
      (PARP1) and the apoptosis-induced factor, suggesting an oxidative influence of
      iodine at high concentrations. Our data indicate that both I(2) and 6-IL trigger
      the same intracellular pathways and suggest that the antineoplasic effect of I(2)
      in mammary cancer involves the intracellular formation of 6-IL. Mammary cancer
      cells are known to contain high concentrations of AA, which might explain why
      I(2) exerts apoptotic effects at lower concentrations only in tumoral cells.

PMID- 18827040
TI  - Quality assessment of phase I dose-finding cancer trials: proposal of a
      checklist.
AB  - BACKGROUND: Qualitative checklists for phase III trials have been proposed, to
      improve the reporting of such trials and to assess the validity of their results.
      PURPOSE: Our objective was to develop such a scale for phase I cancer trials.
      METHODS: From a review of existing guidelines and checklists for phase III
      clinical trials, a staff team was responsible for the first selection of items
      and the construction of the questionnaire. The proposed quality assessment
      measures were rated by the survey respondents comprised of phase I research
      clinicians and statisticians on a 4-point Likert scale. Selected items from the
      quantitative analysis of the questionnaires were reviewed by an expert team who
      was responsible for providing the final items list. This was then applied to 103
      recently published cancer phase I trials. RESULTS: Of the 48 initial items
      proposed by the staff team, 17 were selected from the quantitative analysis of
      the 99 participants' ratings. After qualitative analysis by the expert team, a 15
      item checklist was derived, with 5 items related to trial objective, 5 to design,
      and 5 to analysis. The application to 103 recent journal articles on phase I
      cancer trials evaluating cytotoxic drugs showed on average the report of 10 items
      (range: 6-13) with 4 items reported in more than 95% of papers, while 2 were
      poorly reported. LIMITATIONS: The response rate of participants was 20.7%.
      CONCLUSIONS: A quality assessment checklist was developed for improved critical
      appraisal of the reporting of cytotoxic, dose-finding phase I oncology trials.
      This may be a first step toward a minimum standard of quality measures for all
      phase I clinical trial reports.

PMID- 18827039
TI  - A comprehensive comparison of the continual reassessment method to the standard 3
      + 3 dose escalation scheme in Phase I dose-finding studies.
AB  - BACKGROUND: An extensive literature has covered the statistical properties of the
      Continual Reassessment Method (CRM) and the modifications of this method. While
      there are some applications of CRM designs in recent Phase I trials, the standard
      method (SM) of escalating doses after three patients with an option for an
      additional three patients SM remains very popular, mainly due to its simplicity.
      From a practical perspective, clinicians are interested in designs that can
      estimate the MTD using fewer patients for a fixed number of doses, or can test
      more dose levels for a given sample size. PURPOSE: This article compares CRM
      based methods with the SM in terms of the number of patients needed to reach the
      MTD, total sample size required, and trial duration. METHODS: The comparisons are
      performed under two alternative schemes: a fixed or a varying sample approach
      with the implementation of a stopping rule. The stopping rule halts the trial if
      the confidence interval around the MTD is within a pre-specified bound. Our
      simulations evaluated several CRM-based methods under different scenarios by
      varying the number of dose levels from five to eight and the location of the true
      MTD. RESULTS: CRM and SM are comparable in terms of how fast they reach the MTD
      and the total sample size required when testing a limited number of dose levels
      (<or=5), but as the number of dose levels increases, CRM reaches the MTD in fewer
      patients when used with a fixed sample of 20 patients. However, a sample size of
      20-25 patients is not sufficient to achieve a narrow precision around the
      estimated toxicity rate at the MTD. LIMITATIONS: We focused on methods with
      practical design features that are of interest to clinicians. However, there are
      several alternative CRM-based designs that are not investigated in this
      manuscript, and hence our results are not generalizable to other designs.
      CONCLUSIONS: We show that CRM-based methods are an improvement over the SM in
      terms of accuracy and optimal dose allocation in almost all cases, except when
      the true dose is among the lower levels.

PMID- 18827041
TI  - Sample size calculations for 3-level cluster randomized trials.
AB  - BACKGROUND: The first applications of cluster randomized trials with three
      instead of two levels are beginning to appear in health research, for instance,
      in trials where different strategies to implement best-practice guidelines are
      compared. In such trials, the strategy is implemented in health care units
      ('clusters') and aims at changing the behavior of health care professionals
      working in this unit ('subjects'), while the effects are measured at patient
      level ('evaluations'). PURPOSE: To guide the choice of number of clusters, number
      of subjects per cluster, and number of evaluations per subject. METHODS: We
      derive a sample size formula and investigate the influence of sample allocation
      on power or number of clusters required. RESULTS: The required sample size is the
      product of the sample size in absence of correlation and two variance inflation
      factors (VIFs) that describe the clustering of evaluations within subjects and of
      subjects within cluster, respectively. Because each VIF is expressed in terms of
      an interpretable Pearson correlation, subject matter knowledge can be
      incorporated. Moreover, these Pearson's correlations are related to intracluster
      correlations (ICCs) from comparable, but 2-level cluster randomized trials.
      Formulas are obtained to guide the sample allocation (number of clusters,
      subjects, and evaluations) for minimizing total sample size, minimizing the
      number of clusters, or maximizing power given a budget constraint. LIMITATIONS:
      Empirical estimates of variance components or ICCs from 3-level cluster trials
      are scarce which limits reliably powering. CONCLUSIONS: When parameterized in
      terms of Pearson correlations, the two variance inflation factors give
      quantitative insight into the impact of the number of clusters, subjects and
      evaluations on power. Moreover, subject matter knowledge as well as ICCs from 2
      level cluster randomized trials can be incorporated in the sample size
      calculation, when empirical estimates of variance components or ICCs from a pilot
      or comparable 3-level study are lacking.

PMID- 18827042
TI  - Avoiding verification bias in screening test evaluation in resource poor
      settings: a case study from Zimbabwe.
AB  - BACKGROUND: Verification bias occurs when the percentage of subjects receiving
      disease verification differs according to the test result. Statistical adjustment
      yields unbiased sensitivity and specificity under a missing at random (MAR)
      assumption. PURPOSE: To use an example from an international study to show how
      the assumptions needed for unbiased statistical adjustment for verification bias
      can be undermined by conditions on the ground, and that accuracy of estimates is
      also compromised by too low a sampling fraction of subjects who test negative.
      METHODS: A study in Zimbabwe assessed the accuracy of a screening test for
      cervical cancer screening, visual inspection with acetic acid (VIA). The study
      was conducted in two phases, Phase I, where only 10% of subjects with negative
      tests received verification, and Phase II, in which nearly all subjects were
      verified. Unadjusted, simple- and covariate-adjusted estimates were compared to
      investigate factors affecting differences. Bootstrap simulations were used to
      illustrate the effect of varying test negative sampling fractions. RESULTS: Phase
      I unadjusted sensitivity and specificity were 0.66 (0.61-0.70) and 0.34 (0.31
      0.36), respectively. Simple-weighted adjusted estimators accounting only for VIA
      status were 0.20 (0.17-0.23) and 0.80 (0.78-0.81), respectively, suggesting the
      test to be useless. It was found that verification (colposcopy) capacity in
      country had been exceeded, and that random selection of test negative patients
      for colposcopy had been compromised. Phase II estimates of sensitivity and
      specificity were 0.77 and 0.64, respectively. With 9% disease prevalence, a VIA
      test-negative sampling fraction >50% was necessary for the confidence intervals
      for sensitivity to have more than a 90% probability of including the true value.
      LIMITATIONS: Phase I statistical adjustment was not made for MAR deviations
      unexplained by the two auxiliary factors, Pap results and STD history. Adjustment
      was not possible for other unmeasured co-factors. CONCLUSIONS: While there are
      standard formulae for correcting for verification bias, these will be biased if
      the MAR assumption is not met, which can occur through the actions of study
      personnel or subjects. Design of such studies in low resource environments needs
      to either require 100% verification, or employ procedures ensuring that the
      sample of test negatives who receive verification is indeed random. In addition,
      required test negative sampling fractions need to incorporate information on both
      disease prevalence and overall sample size.

PMID- 18827043
TI  - Recruitment of a racially and ethnically diverse sample into a physical activity
      efficacy trial.
AB  - BACKGROUND: Healthy People 2010 underscores the relevance of eliminating health
      disparities. Thus, it is paramount to create interventions that promote health
      for all individuals. PURPOSE: This study examined differences in rates of and
      reasons for ineligibility among non-Hispanic blacks and whites in a randomized
      controlled physical activity intervention study. METHODS: Participants (1245
      adults) responded to community advertising for the research study. Eligibility at
      the four pre-randomization assessment sessions was determined by self-reported
      medical information, resting EKG, 7-Day Physical Activity Recall, fitness test
      and Stage of Change. We used t-tests to examine the rates of eligibility among
      participant subgroups. RESULTS: Blacks had higher rates of overall ineligibility
      (86.9%) than whites (75.1%; p < 0.01) and were more likely to be ineligible due
      to lack of interest or no-show at a pre-randomization appointment (35.4% vs.
      24.3%; p < 0.01). Blacks were more likely to be ineligible for medical reasons
      after the telephone screen (16.3% vs. 7.8%; p = 0.01). LIMITATIONS: This study
      did not use a random sampling of potential participants from each of the
      racial/ethnic groups and thus, there is the potential for selection bias.
      CONCLUSIONS: Blacks were more likely to choose not to enroll in the study due to
      a lack of interest, but had similar rates of overall medical ineligibility to
      whites. This highlights the importance of strategies that enhance interest among
      blacks, who initially respond to recruitment advertising.

PMID- 18827044
TI  - Clinical trials in stem cell transplantation: guidelines for scientific and
      ethical review.
AB  - BACKGROUND: Transplantation of cells derived through the manipulation of
      pluripotent stem cells may involve great uncertainty and the possibility of
      serious risks. PURPOSE: To develop guidelines for the ethical conduct of clinical
      trials using such stem cells. METHODS: Review of literature on clinical trials
      ethics and clinical applications of stem cells; critical deliberation on
      potential guidelines. RESULTS: Such transplantation should be allowed in clinical
      practice only after clinical trials demonstrate efficacy and safety. These
      clinical trials should follow ethical principles that guide all clinical
      research. Additional requirements to strengthen trial design, coordinate
      scientific and ethics review, verify that participants understand key features of
      the trial, and ensure publication of findings are also warranted because of the
      highly innovative nature of the intervention, limited experience in humans, and
      the high hopes of patients who have no alternative effective treatments.
      LIMITATIONS: These recommendations will need to be modified in light of actual
      experience with stem cell clinical trials. CONCLUSIONS: These recommendations
      will help guarantee that the efficacy and safety of innovative stem cell
      interventions will be rigorously established, while also protecting study
      participants.

PMID- 18827045
TI  - A multi-center, randomized, double blind placebo-controlled trial of estrogens to
      prevent Alzheimer's disease and loss of memory in women: design and baseline
      characteristics.
AB  - BACKGROUND: Observational studies and small clinical trials suggested that
      hormone replacement therapy (HRT) decreases risk of cognitive loss and
      Alzheimer's disease (AD) in postmenopausal women and may have value in primary
      prevention. PURPOSE: A clinical trial was designed to determine if HRT delays AD
      or memory loss. This report describes the rationale and original design of the
      trial and details extensive modifications that were required to respond to
      unanticipated findings that emerged from other studies during the course of the
      trial. METHODS: The trial was designed as a multi-center, placebo-controlled
      primary prevention trial for women 65 years of age or older with a family history
      of dementia. Recruitment from local sites was supplemented by centralized efforts
      to use names of Medicare beneficiaries. Inclusion criteria included good general
      health and intact memory functioning. Participants were randomized to HRT or
      placebo in a 1:1 ratio. Assignment was stratified by hysterectomy status and
      site. The primary outcomes were incident AD and memory decline on
      neuropsychological testing. RESULTS: Enrollment began in March 1998. In response
      to the Women's Health Initiative (WHI) May 2002 report of increased incidence of
      heart disease, stroke, pulmonary embolism, and breast cancer among women
      randomized to HRT, participants were re-consented with a revised consent form.
      Procedural modifications, including discontinuation of study medication and a
      modification of the planned primary outcome based on a final enrollment below the
      target enrollment (N = 477), were enacted in response to the subsequent WHI
      Memory Study report of increased risk of dementia and poorer cognitive function
      with HRT. The mean length of treatment exposure prior to discontinuation was 2.14
      years. Participants' mean age at baseline was 72.8; mean education was 14.2
      years. Minority participation was 19% and 34% had a hysterectomy. The study
      continues to follow these participants for a total of 5 years blind to the
      original medication assignment. LIMITATIONS: Results reported from the WHI during
      the course of this study mandated extensive procedural modifications, including
      discontinuing recruitment before completion and halting study medication.
      Alternative strategies for study redesign that were considered are discussed.

PMID- 18827046
TI  - DISPACT trial: a randomized controlled trial to compare two different surgical
      techniques of DIStal PAnCreaTectomy - study rationale and design.
AB  - BACKGROUND: Surgery is of increasing importance in the treatment and outcome of
      diseases of the pancreas worldwide. The incidence of pancreatic cancer (7-11/
      100,000 per year) has risen over the last years and surgical resection remains
      the only option for definite cure. Twenty-five percent of all resections are left
      of the superior mesenteric vein (distal pancreatectomy) and the appropriate
      closure technique for the pancreatic remnant remains unclear. Pancreatic fistulas
      are the most common (0-40%) and relevant postoperative complication. The optimal
      surgical strategy for pancreatic resection needs to be identified from the large
      number of surgical procedures available today. PURPOSE: To evaluate the
      effectiveness of the two most common surgical techniques for distal
      pancreatectomy: stapler versus hand-sewn closure of the pancreatic remnant.
      METHODS: In order to account for the uncertainty and clinical heterogeneity in
      the management of the pancreatic remnant following distal pancreatectomy, a study
      protocol is developed on the basis of a retrospective survey of patients in a
      center of excellence for pancreatic surgery and a systematic review with meta
      analysis. RESULTS: The DISPACT trial is a multicentered, randomized, controlled
      and patient-and observer-blinded trial using a two-group parallel group
      sequential superiority design to compare the two techniques mentioned above. It
      will include approximately 336 randomized patients at up to 20 centers of
      excellence in pancreatic surgery, who are undergoing elective distal
      pancreatectomy for resectable benign, malign, and neuroendocrine tumors, chronic
      pancreatitis and pseudocysts of the pancreatic body and tail. The combination of
      the rate of postoperative pancreatic fistula and mortality will be evaluated as
      the primary endpoint. In addition, a set of general and surgical parameters will
      be analyzed. Pre-specified treatment manuals and continuous intra-operative
      (photo-documentation of surgical procedures and blinded evaluation thereafter)
      and on-site monitoring will assure that the treatment of the study patients
      conforms to protocol and will minimize clinical heterogeneity. Due to
      uncertainties about the effect sizes of the primary endpoint, an a priori planned
      interim analysis of the primary endpoint will be conducted after 224 evaluable
      patients are selected in order to reassess the initially planned sample size.
      LIMITATIONS: Since pre-existing evidence was limited our initial sample size
      calculation is based on uncertain assumptions and may need to be modified in a
      planned interim analysis. Moreover, since surgical experience remains a potential
      confounder in surgical trials, learning curve bias has to be taken into account
      when analyzing the results. Given the participating trial sites, standardization
      of peri-and postoperative treatment represents a major issue of trial conduct.
      CONCLUSIONS: A group-sequential study design accounts for the uncertainty of pre
      existing evidence. Also, standardization of surgical and postoperative care and
      blinded outcome assessment as well as adjustment for varying surgical expertise
      will contribute to a high validity and generalizability of the results.

PMID- 18827047
TI  - Design considerations and rationale of a multi-center trial to sustain weight
      loss: the Weight Loss Maintenance Trial.
AB  - BACKGROUND: The Weight Loss Maintenance Trial (WLM) is a multi-center,
      randomized, controlled trial that compares the effects of two 30-month
      maintenance interventions, i.e., Personal Contact (PC) and Interactive Technology
      (IT) to a self-directed usual care control group (SD), in overweight or obese
      individuals who are at high risk for cardiovascular disease. PURPOSE: This paper
      provides an overview of the design and methods, and design considerations and
      lessons learned from this trial. METHODS: All participants received a 6-month
      behavioral weight loss program consisting of weekly group sessions. Participants
      who lost 4 kg were randomized to one of three conditions (PC, IT, or SD). The PC
      condition provided monthly contacts with an interventionist primarily via
      telephone and quarterly face-to-face visits. The IT condition provided frequent,
      individualized contact through a tailored, website system. Both the PC and IT
      maintenance programs encouraged the DASH dietary pattern and employed theory
      based behavioral techniques to promote maintenance. RESULTS: Design
      considerations included choice of study population, frequency and type of
      intervention visits, and choice of primary outcome. Overweight or obese persons
      with CVD risk factors were studied. The pros and cons of studying this population
      while excluding others are presented. We studied intervention contact strategies
      that made fewer demands on participant time and travel, while providing frequent
      opportunities for interaction. The primary outcome variable for the trial was
      change in weight from randomization to end of follow-up (30 months). LIMITATIONS:
      Limits to generalizability are discussed. Individuals in need of weight loss
      strategies may have been excluded due to barriers associated with internet use.
      Other participants may have been excluded secondary to a comorbid condition.
      CONCLUSIONS: This paper highlights the design and methods of WLM and informs
      readers of discussions of critical issues and lessons learned from the trial.

PMID- 18827048
TI  - Do we need to adjudicate major clinical events?

PMID- 18827050
TI  - Mechanisms of thrombosis in autoimmune disorders. Foreword.

PMID- 18827051
TI  - Prothrombotic mechanisms based on the impairment of fibrinolysis in the
      antiphospholipid syndrome.
AB  - Antiphospholipid syndrome (APS) is a clinical autoimmune disorder characterised
      by thrombosis, venous or arterial, and recurrent pregnancy morbidity in
      association with the persistence of antiphospholipid antibodies (aPL). The
      clinical variety of aPL ranges from asymptomatic individuals to those with
      multiple organ thromboses and failure developing over a short period, also known
      as catastrophic APS. An increasing number of phospholipid-binding proteins with
      crucial functions in the regulation of blood coagulation and fibrinolysis are
      targeted by APS-related autoantibodies. Disruption of fibrinolysis is one of the
      proposed pathophysiological mechanisms for the APS. There are some experimental
      data for an association between impaired overall fibrinolytic activity and
      autoimmune aPL; however, evidence is still inconclusive and more studies are
      needed in this area. In this article, we review the evidence by which aPL may
      disturb fibrinolysis.

PMID- 18827052
TI  - Autoimmune-mediated atherothrombosis.
AB  - Autoimmune vascular inflammation and oxidative stress (lipid peroxidation) are
      common in systemic autoimmune diseases and contribute to the oxidative
      modification of low-density lipoprotein (oxLDL) and oxLDL/beta2GPI complex
      formation. Circulating oxLDL/beta2GPI complexes have been detected in patients
      with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). The
      presence of antibodies to oxLDL/beta2GPI complexes indicates that these complexes
      are immunogenic, and the coexistence of complexes and antibodies has pointed to
      an active proatherogenic role in the development of autoimmune vascular
      complications. Immunohistochemical staining of atherosclerotic lesions suggest
      that these complexes are formed in the arterial wall and released into
      circulation. The in vitro macrophage uptake of oxLDL/beta2GPI complexes was
      significantly increased in the presence of antiphospholipid antibodies, either
      beta2GPI-dependent anticardiolipin or anti-beta2GPI antibodies, suggesting that
      macrophage Fcgamma receptors are involved in lipid intracellular influx and foam
      cell formation. These findings provide an explanation for the accelerated
      development of atherosclerosis seen in SLE and APS. The presence of circulating
      oxLDL/beta2GPI complexes and IgG antibodies to these complexes indicate
      significant vascular injury and oxidative stress as well as an active role in
      autoimmune-mediated atherothrombosis.

PMID- 18827053
TI  - Platelets and the antiphospholipid syndrome.
AB  - The antiphospholipid syndrome is a non-inflammatory autoimmune disease
      characterised by the presence of antiphospholipid antibodies in the plasma of
      patients with venous or arterial thrombosis or recurrent complications of
      pregnancy. The strong relation between the presence of antibodies against anionic
      phospholipids and thrombo-embolic complications is well established, but how the
      presence of antiphospholipid antibodies results in the observed clinical
      manifestations remains a mystery. Experimental observations suggest that an
      altered regulation of platelet function can cause the thrombotic complications
      observed in the antiphospholipid syndrome. In this review, we will discuss the
      evidence that the platelet is an important player in the pathogenesis of the
      antiphospholipid syndrome.

PMID- 18827054
TI  - Examining the non-linear relationship between monoclonal antiphospholipid
      antibody sequence, structure and function.
AB  - In the antiphospholipid syndrome (APS), pathogenic antiphospholipid antibodies
      (aPL) that cause thrombosis or pregnancy morbidity are characterized by binding
      to anionic phospholipids (PL) and beta2-glycoprotein I (beta(2)GPI). Sequence
      analysis of human monoclonal aPL has shown that high affinity for these antigens
      is associated with the presence of three particular amino acids: arginine (Arg),
      asparagine and lysine in the complementarity determining regions (CDRs) of their
      heavy and light chains. In vitro expression systems have been used to create
      variants of the antibodies in which these amino acids have been altered. In
      general, removal of Arg residues reduces affinity for anionic PL and beta(2)GPI.
      Arg at different positions in the sequence, however, have different effects on
      binding affinity and effects on binding are not always mirrored by effects on
      pathogenicity. This review will focus upon the sequence motifs that have been
      found to distinguish pathogenic from non-pathogenic aPL, and whether these or
      other properties may help to identify distinct pathogenic subsets of aPL. In
      particular, we will focus on our recent work in which we are trying to develop a
      better understanding of the molecular mechanisms involved in activation of target
      cells by pathogenic aPL. These studies, together with molecular models of
      antigen/antibody complexes, help us to understand exactly how pathogenic
      antibodies interact with antigens. Ultimately, this understanding may aid the
      design of more powerful diagnostic/prognostic assays and targeted therapeutic
      agents to block the pathogenic effects of these antibodies.

PMID- 18827055
TI  - Genomics and proteomics: a new approach for assessing thrombotic risk in
      autoimmune diseases.
AB  - Several systemic autoimmune conditions, including rheumatoid arthritis, systemic
      lupus erythematosus and antiphospholipid syndrome, are characterised by enhanced
      atherosclerosis and, consequently, higher cardiovascular morbidity and mortality
      rates. The association of these diseases with atherosclerosis suggests a common
      pathogenic mechanism. Genomic and proteomic studies performed on atherosclerotic
      plaques have further confirmed the presence of a gene and protein profile similar
      to that observed in autoimmune diseases with cardiovascular risks. Human sera and
      body fluids have been analysed and have resulted in the identification of auto
      antibodies that can be used as diagnostic markers in specific autoimmune
      diseases, and proteomic fingerprints of blood cells, tissues and body fluids have
      resulted in the identification of individual proteins or patterns of protein
      expression that are deregulated. The information provided by these proteomic
      studies is of diagnostic and therapeutic potential. In this review, we discuss
      new approaches available for assessing thrombotic risk in autoimmune diseases,
      focusing in the genomic and proteomic methods now available to deep into the
      origin of the mechanisms associated with vascular involvement in systemic
      autoimmune diseases. The increasing data available suggests that when treating
      patients with these autoimmune disorders, paying attention to the increased risk
      of cardiovascular disease is essential.

PMID- 18827056
TI  - Some antiphospholipid antibodies bind to hemostasis and fibrinolysis proteases
      and promote thrombosis.
AB  - It is generally accepted that the major autoantigen for antiphospholipid
      antibodies (aPL) is beta(2)glycoprotein I (beta(2)GPI). Interestingly, some aPL
      bind to beta(2)GPI and the homologous enzymatic domains of several proteases
      involved in hemostasis and fibrinolysis, and correspondingly hinder anticoagulant
      regulation and resolution of clots. These findings are consistent with several
      early findings of aPL and provide a new perspective about some aPL in terms of
      their binding specificities and related functional properties in promoting
      thrombosis. In addition, homologous enzymatic domains of the involved proteases
      share conformation epitope(s) with beta(2)GPI, thus providing a possible
      structural basis for some non-mutually exclusive mechanisms of aPL-mediated
      thrombosis.

PMID- 18827057
TI  - Resistance to annexin A5 anticoagulant activity: a thrombogenic mechanism for the
      antiphospholipid syndrome.
AB  - The phospholipid binding protein, annexin A5 (AnxA5), has potent anticoagulant
      properties that result from its forming 2-dimensional crystals over
      phospholipids, blocking the availability of the phospholipids for critical
      coagulation enzyme reactions. This article reviews the evidence that
      antiphospholipid antibodies can disrupt this anticoagulant shield and unmask
      thrombogenic anionic phospholipids, which may thereby contribute to thrombosis in
      patients with the antiphospholipid syndrome (APS). This mechanism for thrombosis
      in APS can be monitored with coagulation assays for resistance to anticoagulant
      activity of AnxA5.

PMID- 18827058
TI  - Tissue factor in antiphospholipid antibody-induced pregnancy loss: a pro
      inflammatory molecule.
AB  - Fetal loss in patients with antiphospholipid antibodies (aPL) has been ascribed
      to thrombosis of placental vessels. However, we have shown that inflammation,
      specifically complement activation with generation of the anaphylotoxin C5a, is
      an essential mediator of fetal injury. We have analysed the role of tissue factor
      (TF) in a mouse model of aPL-induced pregnancy loss. TF is the major cellular
      activator of the coagulation cascade but also has cell signaling activity. Mice
      that received aPL-IgG showed strong TF staining throughout the decidua and on
      embryonic debris. This TF staining was not associated with either fibrin staining
      or thrombi in deciduas. The absence of fibrin deposition and thrombi suggests
      that TF-dependent activation of coagulation does not mediate aPL-induced
      pregnancy loss.We found that either blockade of TF with a monoclonal antibody in
      wild type mice or a genetic reduction of TF prevented aPL-induced inflammation
      and pregnancy loss indicated a pathogenic role for TF in aPL-induced pregnancy
      complications. In response to aPL-generated C5a, neutrophils express TF
      potentiating inflammation in the deciduas and leading to miscarriages.
      Importantly, we showed that TF in myeloid cells, but not fetal-derived cells
      (trophoblasts), was associated with fetal injury, suggesting that the site for
      pathologic TF expression is neutrophils. We found that TF expression in
      neutrophils contributes to respiratory burst and subsequent trophoblast injury
      and pregnancy loss induced by aPL. The identification of TF, acting as an
      important pro-inflammatory mediator in aPL-induced fetal injury, provides a new
      target for therapy to prevent pregnancy loss in the aPL syndrome.

PMID- 18827059
TI  - Toll-like receptors: another player in the pathogenesis of the anti-phospholipid
      syndrome.
AB  - The anti-phospholipid syndrome (APS) is a systemic autoimmune disease
      characterized by an adaptive immune response against self phospholipid (PL)-
      binding proteins. Although APS is considered as an autoantibody-mediated disease,
      there is now evidence that anti-phospholipid antibodies (aPL) are necessary but
      not sufficient to trigger some of the clinical manifestations of the syndrome.
      For example, mediators of the innate immunity are recognized to be additional
      second hits able to induce the thrombotic events in the presence of aPL. Finally,
      environmental agents - in particular infectious ones - were reported to act as
      triggers for the production of autoantibodies cross-reacting with PL-binding
      proteins as well as inflammatory stimuli that potentiate the aPL thrombogenic
      effect. Altogether, these findings suggest a role for the innate immunity in APS
      pathogenesis. Toll-like receptors (TLR) are receptors that induce prompt
      inflammatory responses and mediate functional activation in immune effector
      cells. There is evidence that aPL, and in particular anti-beta(2) glycoprotein I
      (beta(2)GPI) antibodies, may activate endothelial cells and monocytes through TLR
      4-dependent signalling. Whether or not TLR may behave as surface receptors for
      beta(2)GPI is still matter of research. Drugs or molecules able to interfere with
      TLR involvement may represent new therapeutic approaches for APS.

PMID- 18827060
TI  - Annexin A2: biology and relevance to the antiphospholipid syndrome.
AB  - Antiphospholipid antibodies (aPL), the majority of which are directed against
      beta(2)-glycoprotein I (beta(2)GPI), are associated with an increased incidence
      of venous and arterial thrombosis. The pathogenesis of antiphospholipid/anti
      beta(2)GPI-associated thrombosis has not been defined, and is likely
      multifactorial. However, accumulating evidence suggests an important role for
      endothelial cell activation with the acquisition of a procoagulant phenotype by
      the activated endothelial cell. Previous work demonstrated that endothelial
      activation by antiphospholipid/anti-beta(2)GPI antibodies is beta(2)GPI
      dependent. We extended these observations by defining annexin A2 as an
      endothelial beta(2)GPI binding site. We also observed that annexin A2 plays a
      critical role in endothelial cell activation induced by anti-beta(2)GPI
      antibodies, and others have described direct endothelial activation by anti
      annexin A2 antibodies in patients with aPL . Similar findings have been reported
      using human monocytes, which also express annexin A2. Because annexin A2 is not a
      transmembrane protein, how binding of beta(2)GPI/anti-beta(2)GPI antibodies, or
      anti-annexin A2 antibodies, to endothelial annexin A2 causes cellular activation
      is unknown. Recent studies, however, suggest an important role for the Toll-like
      receptor family, particularly TLR4. In this article, we review the role of these
      interactions in the activation of endothelial cells by aPL . The influence of
      these antibodies on the ability of annexin A2 to enhance t-PA-mediated
      plasminogen activation is also discussed.

PMID- 18827061
TI  - Tissue factor in the antiphospholipid syndrome.
AB  - Antiphospholipid (aPL) antibodies are clinically important acquired risk factors
      for thrombosis and pregnancy loss and are thought to have a direct prothrombotic
      effect in vivo. Data suggest that a major mechanism by which aPL antibodies
      contribute to thrombophilia is the upregulation of tissue factor (TF) (CD142) on
      blood cells and vascular endothelium. TF is the physiological trigger of normal
      blood coagulation and thrombosis in many hypercoagulable conditions. This article
      reviews the physiology of TF, the molecular regulation of TF expression and the
      effects of aPL antibodies on intravascular TF regulation and expression.
      Inhibition of TF and the pathways by which aPL antibodies induce TF expression
      are potentially attractive therapeutic targets in the antiphospholipid syndrome.

PMID- 18827063
TI  - Long-term effects of cardiac resynchronization therapy in octogenarians: a
      comparative study with a younger population.
AB  - AIMS: Heart failure is a disease of octogenarians. The evidence base for cardiac
      resynchronization therapy (CRT) has emerged from trials of patients in their 60s.
      We compared the effectiveness of CRT in octogenerians with younger patients.
      METHODS AND RESULTS: Patients aged >or=80 years [n = 53, age 83.7 +/- 2.6 years
      (mean +/- SD)] and <80 years (n = 277, age 66.9 +/- 9.5 years) with ischaemic or
      non-ischaemic cardiomyopathy (NYHA class III or IV heart failure, left
      ventricular ejection fraction <35%, QRS >or= 120 ms) underwent CRT. A clinical
      assessment, including a 6-min walk test, and a quality of life assessment
      (Minnesota Living with Heart Failure questionnaire) were undertaken at baseline
      and after CRT. In octogenarians, CRT was associated with similar changes in NYHA
      class [-1.28 vs. -1.22, P < 0.0001 (P-values refer to changes from baseline)], 6
      min walking distance (77.2 vs. 78.6 m, P < 0.0001), and quality of life scores (
      20.4 vs. -31.4, P = 0.0084) to <80 year olds. A symptomatic response to CRT
      (improvement by >or=1 NYHA classes or >or=25% 6-min walking distance) was
      observed in 80% of <80 year olds and in 81% of octogenarians (P = NS). Using a
      combined clinical score (CCS; survival for 1 year with no heart failure
      hospitalizations, and; improvement by >or=1 NYHA classes or >or=25% 6-min walking
      distance), a response was observed in 201 out of 277 (73%) patients <80 years and
      in 36 out of 53 (68%) octogenarians (P = NS). After a maximum follow-up of 7.6
      years (median 634 days), no group differences emerged with respect to the
      composite endpoints of cardiovascular death or hospitalization for major
      cardiovascular events, the composite endpoint of cardiovascular death or heart
      failure hospitalization, cardiovascular mortality, or total mortality.
      CONCLUSION: Octogenarians derive similar benefits from CRT to younger patients.

PMID- 18827062
TI  - Differential selective constraints shaping codon usage pattern of housekeeping
      and tissue-specific homologous genes of rice and arabidopsis.
AB  - Intra-genomic variation between housekeeping and tissue-specific genes has always
      been a study of interest in higher eukaryotes. To-date, however, no such
      investigation has been done in plants. Availability of whole genome expression
      data for both rice and Arabidopsis has made it possible to examine the
      evolutionary forces in shaping codon usage pattern in both housekeeping and
      tissue-specific genes in plants. In the present work, we have taken 4065 rice
      Arabidopsis homologous gene pairs to study evolutionary forces responsible for
      codon usage divergence between housekeeping and tissue-specific genes. In both
      rice and Arabidopsis, it is mutational bias that regulates error minimization in
      highly expressed genes of both housekeeping and tissue-specific genes. Our
      results show that, in comparison to tissue-specific genes, housekeeping genes are
      under strong selective constraint in plants. However, in tissue-specific genes,
      lowly expressed genes are under stronger selective constraint compared with
      highly expressed genes. We demonstrated that constraint acting on mRNA secondary
      structure is responsible for modulating codon usage variations in rice tissue
      specific genes. Thus, different evolutionary forces must underline the evolution
      of synonymous codon usage of highly expressed genes of housekeeping and tissue
      specific genes in rice and Arabidopsis.

PMID- 18827064
TI  - The appearance of the adrenal glands on computed tomography in multiple endocrine
      neoplasia type 1.
AB  - AIMS: To review the morphology of the adrenal glands in multiple endocrine
      neoplasia type 1 (MEN1) on computed tomography (CT) to compare the results with
      established normal values for adrenal size and nodularity and to correlate
      adrenal size with serum cortisol secretory dynamics. MATERIALS AND METHODS: Two
      observers independently reviewed the adrenal CT in 28 patients with MEN1,
      measuring the maximum width of the body of the gland and the medial and lateral
      limbs. Incidence and location of nodules >5 mm within the gland were recorded.
      Following exclusion of known cases of Cushing's syndrome, adrenal gland size was
      compared with previously documented normative data. Adrenal gland size was
      compared between patients with normal and abnormal cortisol dynamics. RESULTS:
      Comparison of mean adrenal size in MEN1 patients with normative data showed that
      the adrenal limbs were significantly larger in MEN1 than normal (P<0.0001 in all
      four limbs). Adrenal body was also significantly larger (P<0.05). Nodules were
      demonstrated in 17 (60%) of patients (versus 0.4-2% in the normal population). No
      statistically significant correlation was demonstrated between adrenal limb
      hyperplasia and abnormal cortisol dynamics. CONCLUSIONS: In patients with MEN1,
      adrenal limb hyperplasia and adrenal nodules are significantly more common than
      in the normal population, a phenomenon not previously documented in a
      quantitative manner. There was no significant correlation between adrenal limb
      hyperplasia and abnormal cortisol dynamics.

PMID- 18827065
TI  - Awakening the oocyte: controlling primordial follicle development.
AB  - Oocytes are sequestered in primordial follicles before birth and remain quiescent
      in the ovary, often for decades, until recruited into the growing pool throughout
      the reproductive years. Therefore, activation of follicle growth is a major
      biological checkpoint that controls female reproductive potential. However, we
      are only just beginning to elucidate the cellular mechanisms required for either
      maintenance of the quiescent primordial follicle pool or initiation of follicle
      growth. Understanding the intracellular signalling systems that control oocyte
      maintenance and activation has significant implications for improving female
      reproductive productivity and longevity in mammals, and has application in
      domestic animal husbandry, feral animal population control and infertility in
      women.

PMID- 18827066
TI  - Cytogenetic damage in preimplantation mouse embryos generated after paternal and
      parental gamma-irradiation and the influence of vitamin C.
AB  - Cytogenetic damage expressed as micronuclei (MN) in 4-8-cell embryos generated
      after irradiation of male or male and female mice in the absence and presence of
      vitamin C was investigated. Male NMRI mice were whole body exposed to 4 Gy gamma
      rays and mated with non-irradiated superovulated female mice in 6 successive
      weeks after irradiation in a weekly interval. In experiments involving
      irradiation of both male and female mice, irradiated male mice for 6 weeks post
      irradiation were mated with female mice irradiated after induction of
      superovulation. Effect of 100 mg/kg vitamin C (ascorbic acid) on the frequency of
      MN was also studied. Pregnant animals were euthanized and embryos flushed from
      the oviducts and fixed on slides. The rate of MN observed in embryos generated
      from irradiated male compared with control group dramatically increased (P<0.01).
      Frequency of MN in this group decreased dramatically after vitamin C treatment
      (P<0.01). Frequency of MN in embryos generated by mating both male and female
      irradiated mice was higher than that observed for those embryos generated by
      irradiated male mice alone. However, a considerable modifying effect of vitamin C
      was observed for this group too (P<0.05). Results indicate that irradiation of
      gonads during spermatogenesis and preovulatory stage oocytes may lead to unstable
      chromosomal aberrations and probably stable chromosomal abnormalities affecting
      pairing and disjunction of chromosomes in successive preimplantation embryos
      expressed as MN. The way vitamin C reduces clastogenic effects of radiation on
      germ cells leading to reduced frequency of MN in pre-embryos might be due to its
      antioxidation and radical scavenging properties.

PMID- 18827067
TI  - Liver-derived IGF1 enhances the androgenic response in prostate.
AB  - Both IGF1 and androgens are major enhancers of prostate growth and are implicated
      in the development of prostate hyperplasia and cancer. The aim of the present
      study was to investigate whether liver-derived endocrine IGF1 modulates the
      androgenic response in prostate. Mice with adult, liver-specific inactivation of
      IGF1 (LI-IGF1(-/-) mice) displayed an approximately 80% reduction in serum IGF1
      levels associated with decreased prostate weight compared with control mice
      (anterior prostate lobe -19%, P<0.05; dorsolateral prostate (DLP) lobe -35%,
      P<0.01; ventral prostate (VP) lobe -47%, P<0.01). Reduced androgen receptor (Ar)
      mRNA and protein levels were observed in the VP lobe (-34% and -30% respectively,
      both P<0.05 versus control mice). Analysis of prostate morphology showed
      reductions in both the glandular and fibromuscular compartments of the VP and DLP
      lobes that were proportional to the reductions in the weights of these lobes.
      Immunohistochemistry revealed reduced intracellular AR immunoreactivity in the VP
      and DLP lobes. The non-aromatizable androgen dihydrotestosterone increased VP
      weight to a lesser extent in orchidectomized (ORX) LI-IGF1(-/-) mice than in ORX
      controls (-40%, P<0.05 versus control mice). In conclusion, deficiency of liver
      derived IGF1 reduces both the glandular and fibromuscular compartments of the
      prostate, decreases AR expression in prostate, and reduces the stimulatory effect
      of androgens on VP weight. These findings may explain, at least in part, the well
      known clinical association between serum IGF1 levels and conditions with abnormal
      prostate growth.

PMID- 18827068
TI  - Security of knots tied with ethibond, fiberwire, orthocord, or ultrabraid.
AB  - BACKGROUND: The security of several popular arthroscopic knots to prolonged,
      incremental, cyclic loads is unknown, as is the security of knots tied with
      newer, superstrong sutures. HYPOTHESIS: Some arthroscopic knots are as secure as
      openly tied square knots, and knots tied with superstrong sutures are more secure
      than those tied with braided polyester. Some arthroscopic knots are significantly
      bulkier than openly tied square knots. STUDY DESIGN: Controlled laboratory study.
      METHODS: Five types of openly tied knots (3-throw square, 4-throw square, 5-throw
      square, 5-throw slip, open SAK [simple arthroscopic knot]), 6 complex
      arthroscopic knots backed with 3 reversed half-hitches with alternating posts
      (RHAPs) (SMC, Weston, taut-line hitch, Tennessee slider, Roeder, Duncan loop),
      and 2 stacked half-hitch (SHH) arthroscopic knots (surgeon's [S=S=S//xS//xS//xS],
      SAK [S=S//xSxS//xS]) were tied using No. 2 Ethibond around 2 aluminum rods, which
      were pulled apart with stepwise, incremental, cyclic loads to a maximum force of
      120 N (2250 total cycles). Then, 5-throw square knots openly tied with No. 2
      Fiberwire, Orthocord, or Ultrabraid were subjected to the stepwise, incremental,
      cyclic loading protocol extended to a 260-N load level. Before mechanical
      testing, the height (maximum diameter) of each knot was measured with digital
      calipers. RESULTS: For Ethibond, the openly tied 3-throw square knots (56.2 +/-
      21.4 N) and 5-throw slip knots (49.9 +/- 26.9 N) reached clinical failure (3 mm
      of laxity) at significantly lower loads (P < .05) than openly tied 5-throw square
      knots (90.8 +/- 6.5 N), whereas the openly tied SAK (82.3 +/- 9.4 N) and 4-throw
      square (84.3 +/- 11.6 N) and all arthroscopically tied knots reached 3 mm of
      laxity at statistically similar loads. Five-throw square knots openly tied with
      Fiberwire or Orthocord reached 3 mm of laxity at much higher loads (194.9 +/-
      28.4 N and 168.4 +/- 8.6 N, respectively) than those tied using Ethibond (P <
      .001 for each comparison), but there was no significant difference in performance
      between Fiberwire knots and Orthocord knots. Although Ultrabraid square knots
      also were stronger than those tied with Ethibond (137.9 +/- 15.9 N, P < .005),
      they were not as secure as those tied with Orthocord or Fiberwire (P < .05).
      Compared with the 5-throw square knots, all arthroscopic knots were significantly
      bulkier. Especially bulky knots were the Duncan loop and the taut-line hitch.
      Orthocord square knots demonstrated bulkiness similar to Ethibond square knots,
      whereas Fiberwire and Ultrabraid square knots were significantly bulkier.
      CONCLUSIONS: For braided suture, 5-throw knots optimize square knot security.
      Open or arthroscopic slip knots can achieve similar security with post switching
      and loop reversal. Fiberwire, Orthocord, or Ultrabraid openly tied square knots
      offer greater security than those tied with Ethibond. Arthroscopic knots vary in
      their bulkiness, but all are significantly bulkier than 5-throw openly tied
      square knots. Square knots openly tied with Fiberwire or Ultrabraid tend to be
      bulkier than if tied with Ethibond or Orthocord, which are similar to each other.
      CLINICAL RELEVANCE: The 5-throw openly tied square knot remains the gold
      standard, although the openly tied SAK offers similar security when tying in a
      hole. Arthroscopic knots, whether complex knots backed up by 3 RHAPs, the 6-throw
      surgeon's knot, or the 5-throw SAK, give security similar to the standard. Square
      knots tied with the newer sutures in open fashion are more secure than if tied
      with braided polyester. Using lower profile knots may be especially important
      when employing Fiberwire or Ultrabraid, as these sutures tend to result in
      bulkier knots than those tied with Ethibond or Orthocord.

PMID- 18827069
TI  - Use of a nasal bridle prevents accidental nasoenteral feeding tube removal.
AB  - Reinserting feeding tubes that are accidentally removed exposes patients to risk
      and consumes hospital resources. We were interested to know if using a bridle to
      secure tubes would be more effective than tape at preventing accidental tube
      removal. This was a quality improvement project with a before-and-after design.
      Between May 2007 and August 2007, we prospectively followed 90 tubes (50 tape, 40
      bridle). Tubes were followed up daily until accidental tube removal, ICU
      discharge, or planned tube removal. Our primary endpoint was accidental tube
      removal. We compared the 2 groups on the following: (1) proportion of tubes
      accidentally removed; (2) rate of accidental tube removal (per 100 tube-days);
      and (3) Kaplan-Meier survival analysis. Survival analysis data were right
      censored at ICU discharge or planned tube removal. There were no significant
      differences between groups in any demographics. The proportion of tubes
      accidentally removed was 36% (18 of 50) in the tape group and 10% (4 of 40) in
      the bridle group; P<.05. The rate of accidental tube removal (per 100 tube-days)
      was 6.4 (18 in 281 tube-days) in the tape group and 1.6 (4 in 248 tube-days) in
      the bridle group; P<.05. Survival analysis showed a significant difference
      between the groups with a log-rank test for equality of survivor function of
      P<.05. Using a bridle to secure feeding tubes significantly reduces the
      proportion and rate of accidental tube removal and results in increased tube
      survival by Kaplan-Meier analysis.

PMID- 18827070
TI  - Dementia and cognitive impairment are not associated with earlier mortality after
      percutaneous endoscopic gastrostomy.
AB  - BACKGROUND: Studies have shown varying results with regard to risk factors for
      mortality after percutaneous endoscopic gastrostomy (PEG). OBJECTIVES: To examine
      the time to death in patients with dementia or significant cognitive impairment
      (SCI) due to neurologic injury who had undergone PEG compared with patients
      without either of these diagnoses, and to examine risk factors for 30-day
      mortality after PEG. METHODS: Patients who had undergone PEG over a 2-year period
      were identified. Local medical records and the Social Security Death Index were
      reviewed to ascertain the patients' age, gender, serum albumin, diagnoses,
      presence or absence of dementia or SCI, presence or absence of complications
      related to PEG, and length of survival after PEG. The Charlson Comorbidity Index
      (CCI) was calculated based on the medical diagnoses at the time of PEG. RESULTS:
      One hundred ninety patients were identified. Forty-five carried a diagnosis of
      dementia and/or SCI compared with 145 who did not. Median survival of patients
      with dementia or SCI was 53 days compared with 78 days in patients without these
      diagnoses (P=.85). Age (odds ratio [OR] 1.1, 95% confidence interval [CI] 1.04
      1.12) and albumin (OR 0.43, 95% CI 0.22-0.84) were associated with 30-day
      mortality, whereas gender (OR 1.2, 95% CI 0.47-2.90), CCI (OR 1.1, 95% CI 0.86
      1.32), and presence of PEG-related complications (OR 1.6, 95% CI 0.36-6.76) were
      not. CONCLUSIONS: Age and serum albumin are risk factors for 30-day mortality
      after PEG. Patients with dementia or SCI do not have a significantly shorter
      survival after PEG than patients with intact cognitive function.

PMID- 18827071
TI  - Feasibility of self-propelling nasojejunal feeding tube in patients with acute
      pancreatitis.
AB  - BACKGROUND & AIMS: To assess the success rate of a self-propelling nasojejunal
      feeding tube in patients with acute pancreatitis. METHODS: All patients admitted
      for acute pancreatitis were included. A self-propelling nasojejunal feeding tube
      was introduced into the stomach, and gastrointestinal motility was stimulated
      using metoclopramide. If the tube failed to advance to the ligament of Treitz, a
      nasojejunal tube was placed endoscopically. RESULTS: A total of 108 patients, 94
      with necrotizing pancreatitis (Balthazar D/E) and 14 with nonnecrotizing
      pancreatitis (Balthazar B/C), were referred for artificial nutrition. In 11
      cases, ileus persisted and parenteral nutrition was initiated. Among the
      remaining 97 patients, 5 refused tube placement. The self-propelling feeding tube
      was inserted in 92 patients with successful migration to the ligament of Treitz
      in 61% (n = 56) and failure in 39% (n = 36). Of the 36 patients with an initial
      failed placement, endoscopic placement of a nasojejunal tube was successful 80%
      of the time (29 patients). The success rate of a nasojejunal self-propelling
      feeding tube placement correlated directly with the severity of the acute
      pancreatitis (92% in B/C vs 61% in D vs 48% in E; P < .05). CONCLUSIONS: Use of a
      self-propelling nasojejunal tube is a simple technique that can be successfully
      performed in the majority of patients with acute pancreatitis. The utility of
      this procedure in the most severe cases of acute pancreatitis continues to pose a
      challenge.

PMID- 18827072
TI  - N-Methyl-N-Nitrosourea (MNU): A positive control chemical for p53+/- mouse
      carcinogenicity studies.
AB  - This study evaluated the effects of a single intraperitoneal injection of N
      methyl-N-nitrosourea (MNU) in citrate buffer (pH 4.5) at a dose of 75 mg/kg in
      thirty male and thirty female p53+/- mice followed by a six-month observation
      period. Fifteen control mice per sex received a single intraperitoneal injection
      of citrate buffer. Fifty-six of sixty mice treated with MNU died or were
      sacrificed before the end of the observation period. Twenty-four males and twenty
      seven females treated with MNU developed malignant lymphoma of the thymus; of
      these, twenty-three males and twenty-seven females had corresponding enlargement
      or masses in the thymus at necropsy. Lymphoblasts in thymic lymphomas stained
      positively for mouse CD3 antigen, indicating a T-cell lineage. One control female
      mouse had malignant lymphoma of the spleen that did not involve the thymus. Nine
      males and five females treated with MNU had adenomas or adenocarcinomas of the
      small intestine, whereas no intestinal neoplasms were observed in control mice.
      These findings support the use of a single dose of MNU as a positive control
      chemical in six-month p53+/- mouse carcinogenicity studies and suggest that
      examination of the thymus alone is sufficient to evaluate the validity of the
      model system.

PMID- 18827073
TI  - Variability in weight and histological appearance of the prostate of beagle dogs
      used in toxicology studies.
AB  - This review was performed to assess variations in weight and histologic
      appearance of the prostate of untreated male beagle dogs between 23 and 108 weeks
      of age, from two breeding centers. Data from 125 control beagle dogs from twenty
      seven regulatory toxicology studies were used. Age, terminal body weight, and
      prostate weight were analyzed. Prostate sections were examined microscopically,
      and histological changes-such as development of acini, amount of secretion, and
      patterns of dilation and inflammation-were recorded and graded when appropriate.
      The influence of age, terminal body weight, and source on the weight and
      histological appearance of the prostate, and the degree of interanimal variation
      were evaluated.

PMID- 18827074
TI  - Clinical pharmacokinetics of XP13512, a novel transported prodrug of gabapentin.
AB  - Gabapentin absorption occurs in only a limited region of the small intestine and
      saturates at doses used clinically, resulting in dose-dependent pharmacokinetics,
      high interpatient variability, and potentially ineffective drug exposure.
      XP13512/GSK1838262 is a novel transported prodrug of gabapentin that is absorbed
      throughout the entire length of the intestine by high-capacity nutrient
      transporters. In 4 studies of healthy volunteers (136 subjects total), the
      pharmacokinetics of XP13512 immediate- and extended-release formulations were
      compared with those of oral gabapentin. XP13512 immediate-release (up to 2800 mg
      single dose and 2100 mg twice daily) was well absorbed (>68%, based on urinary
      recovery of gabapentin), converted rapidly to gabapentin, and provided dose
      proportional exposure, whereas absorption of oral gabapentin declined with
      increasing doses to <27% at 1200 mg. Compared with 600 mg gabapentin, an
      equimolar XP13512 extended-release dose provided extended gabapentin exposure
      (time to maximum concentration, 8.4 vs 2.7 hours) and superior bioavailability
      (74.5% vs 36.6%). XP13512 may therefore provide more predictable gabapentin
      exposure and decreased dosing frequency.

PMID- 18827075
TI  - Pharmacokinetics and pharmacodynamics of dabigatran etexilate, an oral direct
      thrombin inhibitor, are not affected by moderate hepatic impairment.
AB  - The impact of moderate hepatic impairment on the pharmacokinetics (PK) and
      pharmacodynamics (PD) of dabigatran etexilate was evaluated in an open, parallel
      group study. Healthy volunteers (n = 12) and patients with hepatic impairment
      (Child-Pugh classification B; n = 12) received a single oral dose of 150 mg
      dabigatran etexilate. The mean values for area under the concentration-time
      curve, terminal half-life, and renal clearance of dabigatran were comparable
      between patients with hepatic impairment and healthy volunteers. Conversion of
      the dabigatran intermediate BIBR1087 to active dabigatran was slower in patients
      with hepatic impairment, indicating that the liver is partly involved in
      bioconversion of dabigatran etexilate. However, total drug exposure was
      comparable between groups; therefore, this observation is of no clinical
      relevance with respect to the anticoagulant activity of dabigatran. The extent of
      dabigatran glucuronidation was unchanged by liver disease; glucuronidation
      capacity was maintained in moderate liver disease. The activated partial
      thromboplastin time, ecarin clotting time, and thrombin time relationships were
      essentially identical in both groups. This study shows that moderate hepatic
      impairment does not affect the PK/PD or safety profile of dabigatran. Therefore,
      patients with moderate hepatic impairment can be given dabigatran etexilate
      without the need for dose adjustment.

PMID- 18827079
TI  - Calling all preceptors: how can we better prepare and support you?

PMID- 18827080
TI  - By the bedside: role of nurses in my journey to recovery.

PMID- 18827082
TI  - Tier approach to propofol infusion syndrome.

PMID- 18827083
TI  - Propofol-induced Brugada electrocardiographic pattern.

PMID- 18827084
TI  - Nerve stimulation in the setting of pharmacologic blockade.

PMID- 18827085
TI  - Management of patients after percutaneous coronary interventions.

PMID- 18827086
TI  - Systolic heart failure in a patient with hypertrophic obstructive cardiomyopathy:
      a potentially life-threatening complication.

PMID- 18827087
TI  - Improving medication adherence in chronic cardiovascular disease.

PMID- 18827088
TI  - Leadership agenda for change toward healthy work environments in acute and
      critical care.

PMID- 18827089
TI  - Brace yourself. Here comes generation Y.

PMID- 18827090
TI  - Delegation considerations for nursing practice.

PMID- 18827091
TI  - Dysrhythmia monitoring.

PMID- 18827093
TI  - Family presence at the bedside.

PMID- 18827094
TI  - Preimplantation genetic diagnosis: a step by step guide to recent Italian ethical
      and legislative troubles.
AB  - OBJECTIVE: To analyse legislation and medical professionals' position concerning
      the doctor's role in assisted reproduction techniques in Italy, and to discuss
      the implications for physicians of preimplantation genetic diagnosis (PGD).
      BACKGROUND: Until recently a strict interpretation of the assisted reproduction
      law (40/2004) and the guidelines subsequently issued, lead to denying infertile
      couples affected by genetic diseases the right to resort to PGD. In October 2006
      the Constitutional Court ruled regarding the question of the constitutional
      legitimacy of the prohibition of PGD. DISCUSSION: The Constitutional Court
      declared the manifest inadmissibility of the question of the constitutional
      legitimacy of article 13 of law 40/2004. The debate has become very animated
      since the ruling. After the negative sentence of the Constitutional Court, three
      further sentences recognised the right of couples to obtain PGD, representing a
      hard blow to law 40/2004 and to the ministerial guidelines; a further
      confirmation of the untenability of a law that violates fundamental principles
      such as the right to healthcare for women and the unborn child, the right to
      responsible motherhood and to informed consent. CONCLUSION: It seems that in
      Italy the legislative inadequacy for medically assisted procreation is reprieved
      by the courageous decisions of the judges, which refer to the values of the
      Italian Constitution, in defence of the fundamental rights of the citizens.

PMID- 18827095
TI  - Telesurgery: an ethical appraisal.
AB  - The aim of this article is to provide a preliminary ethical evaluation of the
      effect of telesurgery (long distance, remote surgery) on patient care. In order
      to accomplish this task we give a broad description of the state of the art in
      telesurgery and analyse it using Joan Tronto's articulation of care as a
      structured process. This structure illuminates the significance of the patient
      physician relationship as the buttress for establishing and preserving practices
      of care in the healthcare context, with the ultimate goal of safeguarding patient
      dignity. The process of care combined with the moral aim of medicine--to fulfil
      the good of the patient--provides the ethical foundation for assessing
      telesurgery. By exploring various telesurgical scenarios we may assess its
      potential role in augmenting or diminishing patient care within the frame of the
      patient-physician relationship. The significance of conducting this evaluation
      lies in the fact that the practice of telesurgery may very shortly become routine
      and an evaluation has not yet been attempted.

PMID- 18827096
TI  - Are decisions about hospital design made upside down?

PMID- 18827097
TI  - Delivery of ambulance service by volunteers in Victoria, Australia: an ethical
      dilemma?
AB  - The Alexandra District Ambulance Service is the only volunteer-based ambulance
      service in Victoria, Australia. It provides an opportunity to reflect on the
      ethical issues surrounding the delivery of ambulance service by volunteers, and
      its impact on the community.

PMID- 18827098
TI  - Theological reflections on donation after circulatory death: the wisdom of Paul
      Ramsey and Moshe Feinstein.
AB  - Due to the worldwide shortage of organs for transplantation, there has been an
      increased use of organs obtained after circulatory death alone. A protocol for
      this procedure has recently been approved by a major transplant consortium. This
      development raises serious moral and ethical concerns. Two renowned theologians
      of the previous generation, Paul Ramsey and Moshe Feinstein, wrote extensively on
      the ethical issues relating to transplantation, and their work has much relevance
      to current moral dilemmas. Their writings relating to definition of death, organ
      transplantation and the care of the terminally ill are briefly presented, and
      their potential application to the moral problem of organ donation after
      circulatory death is discussed.

PMID- 18827099
TI  - The ethics of paediatric anti-depressant use: erring on the side of caution.
AB  - This paper aims to outline the ethical concerns regarding the use of
      antidepressant medication in children and adolescents. Recent debates surrounding
      this issue have focused on the link between selective serotonin reuptake
      inhibitor use and an increased risk of suicidal thinking/behaviour, and weighed
      that against the benefit of the alleviation of depressive symptoms. It is argued
      here that such an approach is simplistic. There are several serious risks
      surrounding antidepressant use in the young that ought to be included in the
      equation, along with a consideration of the neuroethical concerns surrounding
      pharmacotherapy for affective disorders. Using the precautionary principle as a
      framework for analysis it is concluded that the risks are sufficiently serious
      and plausible that the prescribing of antidepressant medication to the young
      ought to be severely restricted; further it is imperative that the child and
      their parents are made fully aware of the risks, short-term and long-term,
      involved.

PMID- 18827100
TI  - Personality disorder and competence to refuse treatment.
AB  - The traditional view that having a personality disorder, unlike other mental
      disorders, is not usually reason enough to consider a person incompetent to make
      healthcare decisions is challenged. The example of a case in which a woman was
      treated for a physical disorder without her consent illustrates that personality
      disorder can render a person incompetent to refuse essential treatment,
      particularly because it can affect the doctor-patient relationship within which
      consent is given.

PMID- 18827101
TI  - Do faculty and resident physicians discuss their medical errors?
AB  - BACKGROUND: Discussions about medical errors facilitate professional learning for
      physicians and may provide emotional support after an error, but little is known
      about physicians' attitudes and practices regarding error discussions with
      colleagues. METHODS: Survey of faculty and resident physicians in generalist
      specialties in Midwest, Mid-Atlantic and Northeast regions of the US to
      investigate attitudes and practices regarding error discussions, likelihood of
      discussing hypothetical errors, experience role-modelling error discussions and
      demographic variables. RESULTS: Responses were received from 338 participants
      (response rate = 74%). In all, 73% of respondents indicated they usually discuss
      their mistakes with colleagues, 70% believed discussing mistakes strengthens
      professional relationships and 89% knew at least one colleague who would be a
      supportive listener. Motivations for error discussions included wanting to learn
      whether a colleague would have made the same decision (91%), wanting colleagues
      to learn from the mistake (80%) and wanting to receive support (79%). Given
      hypothetical scenarios, most respondents indicated they would likely discuss an
      error resulting in no harm (77%), minor harm (87%) or major harm (94%). Fifty
      seven percent of physicians had tried to serve as a role model by discussing an
      error and role-modelling was more likely among those who had previously observed
      an error discussion (OR 4.17, CI 2.34 to 7.42). CONCLUSIONS: Most generalist
      physicians in teaching hospitals report that they usually discuss their errors
      with colleagues, and more than half have tried to role-model discussions.
      However, a significant number of these physicians report that they do not usually
      discuss their errors and some do not know colleagues who would be supportive
      listeners.

PMID- 18827102
TI  - Facial allograft transplants: where's the catch?
AB  - Face transplantation--or, more properly, facial allograft transplantation (FAT)-
      generates much public interest and academic debate. In this paper, we suggest
      that it is up to opponents of FAT to make the case for its impermissibility. We
      allow that there is a number of apparently strong arguments that might be
      deployed against FAT. However, all but one of these turn out not to be compelling
      after examination. The remaining argument is not so easily dismissed--but its
      central point is fairly workaday and certainly does not tell us anything about
      FAT in particular. Therefore, qua argument about facial transplant surgery, it
      fails to hit its target. Overall, we conclude that a compelling case against FAT
      remains to be made.

PMID- 18827103
TI  - A critique of "the best secular argument against abortion".
AB  - Don Marquis has put forward a non-religious argument against abortion based on
      what he claims is a morally relevant similarity between killing adult human
      beings and killing fetuses. He asserts that killing adults is wrong because it
      deprives them of their valuable futures. He points out that a fetus's future
      includes everything that is in an adult's future, given that fetuses naturally
      develop into adults. Thus, according to Marquis, killing a fetus deprives it of
      the same sort of valuable future that an adult is deprived of in being killed and
      this makes abortion seriously wrong. Commentators have raised a number of
      objections to Marquis's argument, to which he has satisfactorily responded. In
      this paper, difficulties with Marquis's argument that have not been considered by
      previous commentators are pointed out. A main thesis of this paper is that
      Marquis does not adequately defend his argument against several important
      objections that he himself has raised. These new considerations support the view
      that Marquis's argument is unsuccessful.

PMID- 18827104
TI  - Embryonic stem cells: the disagreement debate and embryonic stem cell research in
      Israel.
AB  - While some people claim that the present disagreement over embryonic stem (ES)
      cell research cannot be resolved, others argue that developing transparency and
      trust are key elements that could resolve the existing disagreements over such
      research. This paper reveals that transparency is not necessarily a requirement
      for advancing ES cell research, since in Israel, for instance, there is (almost)
      no transparency, and research nevertheless flourishes. Moreover, trust is not
      independent of cultural values and religious beliefs. Because of these beliefs,
      the environment in Israel for ES cell research has been pragmatic and liberal.
      The Israeli case illustrates the key role that culture and religion can play in
      biomedical research; it also suggests that as far as cultural values or religious
      beliefs of people in Western countries strongly oppose research on embryonic
      tissue, it would be very difficult, if not impossible, to overcome the
      disagreements.

PMID- 18827105
TI  - Paternity testing requested by private parties in Italy: some ethical
      considerations.
AB  - In Italy, judicial and extrajudicial requests for paternity testing have
      increased in recent years. A retrospective analysis of such private extrajudicial
      requests received by the legal medicine unit of the Department of Environmental
      Medicine and Public Health of Padua University was conducted to identify problem
      areas most helpful in determining whether to accept private parties' requests for
      paternity testing. Such testing is most delicate when a presumptive father may be
      seeking to disown paternity and when testing is wanted without the consent of a
      member of the mother-child-father triangle. Tests that could establish paternity
      where none has been recognised are less problematic, as the child will not lose
      out. Legal and ethical-deontological aspects of consent, of the protection of
      minors and of children's and parents' need for follow-up interviews to deal with
      the outcome of such testing are carefully considered by the Padua University team
      when deciding whether to accept a request for testing. It is argued that because
      such issues are not dealt with by mail-order laboratories, the use of such
      services is inappropriate.

PMID- 18827106
TI  - UNESCO Global Ethics Observatory: database on ethics related legislation and
      guidelines.
AB  - The Database on Ethics Related Legislation and Guidelines was launched in March
      2007 as the fourth database of the UNESCO Global Ethics Observatory system of
      databases in ethics of science and technology. The database offers a collection
      of legal instruments searchable by region, country, bioethical themes, legal
      categories and applicability to specific articles of the UNESCO Universal
      Declaration on Bioethics and Human Rights and International Declaration on Human
      Genetic Data. This paper discusses the background and rationale for the database
      and its role as a consultative and comparative resource hub for the study of
      ethics related legal instruments across the world, with the purpose of informing
      and inspiring relevant stakeholders on the implementation of the principles
      contained within the UNESCO declarations on bioethics.

PMID- 18827107
TI  - Informed consent for the study of retained tissues from postmortem examination
      following sudden infant death.
AB  - OBJECTIVE: To develop an approach for seeking informed consent to examine tissues
      retained from a previous study of sudden infant death syndrome (SIDS) as part of
      a study on asthma, and to document responses and participation rate. DESIGN:
      Pilot open-ended approach to 10 volunteer SIDS parents, followed by staged
      approach (newsletter, mail and telephone call) to seek consent from the target
      SIDS families for the asthma study. PARTICIPANTS: Parents (n = 10) of SIDS
      infants known to SIDS and Kids Victoria and parents of SIDS infants (n = 107)
      from the 1991-2 SIDS in Victoria case-control study. MAIN OUTCOMES: Qualitative
      responses of the piloted parents and study parents, and participation rates.
      RESULTS: The pilot group responses were used to refine the written material to be
      provided. Of the 72 families for which contact details were available, 45 gave
      verbal consent for contact by the Victorian Institute of Forensic Medicine
      regarding the asthma study, three refused and 24 did not respond to two letters.
      Thirty-three completed consent forms, all positive for participation in the
      asthma study, giving a positive response rate of 73% (33/45). CONCLUSIONS: The
      use of postmortem tissue for research is acceptable to the next of kin when an
      approach is sensitive to their concerns and needs and is made by experienced
      counsellors from a familiar organisation. Despite the painful memories evoked by
      the approach of the research group, the acceptance rate among those who could be
      contacted was high.

PMID- 18827108
TI  - Impact of recent legislative bills regarding clinical research on Italian ethics
      committee activity.
AB  - AIMS AND BACKGROUND: The present work assessed the impact of two decrees on
      ethics committees in Italy, aimed at bringing the national laws on the conduct of
      clinical trials into line with the rest of the EC, and regulating and
      facilitating not-for-profit research. MATERIAL AND METHODS: Prospectively
      collected data from an Italian multicentre study were examined with respect to
      the ethics review process. Administrative and time elements of the review process
      were audited. Main outcome measures were time between the application submission
      and the ethics committee definitive opinion, type and number of application
      submission forms, number of ethics committees that refused fee exemption, and
      time between the ethics committee approval and the administrative authorisation.
      RESULTS: A total of 134 local research ethics committees (LRECs) were approached.
      Application submission procedures and application forms varied greatly; paper
      submission was mandatory. The median time from submission to approval was 72
      days. Only two LRECs refused the fee exemption. The median time from LREC
      approval to administrative agreement was 50 days and only 9.6% of local
      authorities came to a verbal agreement with the sponsor. CONCLUSIONS: Italian
      LRECs are still not sufficiently efficient in complying with the Directive
      2001/20/EC requirement (60 days). Better coordination of LRECs work is needed
      although the optimal level of coordination between them is still not known. In
      the meantime, national guidelines are needed concerning the application of
      Directive 2001/20/EC. The behaviour of Italian LRECs towards not-for-profit
      research was excellent although only the fee exemption was requested.

PMID- 18827109
TI  - I don't like that, it's tricking people too much...: acute informed consent to
      participation in a trial of thrombolysis for stroke.
AB  - BACKGROUND: Informed consent is regarded as a contract between autonomous and
      equal parties and requires the elements of information disclosure, understanding,
      voluntariness and consent. The validity of informed consent for critically ill
      patients has been questioned. Little is known about how these patients experience
      the process of consent. OBJECTIVE: The aim of this study was to explore
      critically ill patients' experience with the principle of informed consent in a
      clinical trial and their ability to give valid informed consent. DESIGN: 11
      stroke patients who had been informed about thrombolytic treatment and had been
      through the process of deciding whether or not to participate in a thrombolysis
      trial went through repeated qualitative semistructured interviews. RESULTS: None
      of the patients had any clear understanding of the purpose of the trial. Neither
      did they understand the principles of randomisation and voluntariness. Reasons
      for giving or not giving consent were trust, conceptions of benefits and risks
      and altruism. Several patients found it immoral to involve patients in the
      consent procedure and argued that this was the doctors' responsibility. Others
      argued that it is a duty to question patients and perceived it as a sign of being
      treated with respect and dignity. A majority of the patients found the consent
      process vague and ambiguous. CONCLUSIONS: The results indicate that the principle
      of informed consent from critically ill patients cannot be seen as a contract
      between equal and autonomous parties. Further studies are needed to explore
      critically ill patients' experiences with the process of informed consent.

PMID- 18827110
TI  - Improving the evidence base in palliative medicine: a moral imperative.
AB  - The difficulties of undertaking good quality effectiveness research in palliative
      medicine are well documented. Much of the ethical literature in this area focuses
      on the vulnerability of the palliative care population. It is clear that a wider
      ethical approach will need to be used to justify research in the terminally ill.
      Some themes of ethical thought are underutilised in considering the ethics of
      palliative care research. Three arguments to justify the need for effectiveness
      research in palliative care should be highlighted: (1) there is evidence of an
      untapped altruism amongst the population of palliative care patients who would be
      keen to be involved in such research; (2) traditional Aristotelean and Thomistic
      virtue ethics would point to the need to gain knowledge in and of itself, but
      especially in palliative medicine for the benefit of PATIENTS: virtue also
      accrues in the acquisition of a stock of research experience which in turn makes
      further research feasible; (3) most compellingly, justice would dictate that
      palliative treatments are effective, that futile or useless treatments are
      avoided and that patients are not party to "n of 1" trials by default. The
      current state of the evidence base of effectiveness in palliative care leads us
      to the uncomfortable position where patients are in precisely the position of
      being unwitting participants in "n of 1" clinical trials by default, without
      their explicit consent.

PMID- 18827111
TI  - Failure to report and provide commentary on research ethics board approval and
      informed consent in medical journals.
AB  - BACKGROUND: The Declaration of Helsinki prohibits the publication of articles
      that do not meet defined ethical standards for reporting of research ethics board
      (REB) approval and informed consent. Despite this prohibition and a call to
      highlight the deficiency for the reader, articles with potential ethical
      shortcomings continue to be published. OBJECTIVE: To determine what proportion of
      articles in major medical journals lack statements confirming REB approval and
      informed consent, and whether accompanying commentary alerts readers to this
      deficiency. DESIGN: Retrospective, observational study. SETTING: Online review of
      five major medical journals. POPULATION: All clinical research articles published
      online between 1 January 2005 and 31 December 2006 in the BMJ, Lancet, Annals of
      Internal Medicine, JAMA and the New England Journal of Medicine. MEASUREMENTS:
      Statement of REB approval and informed consent. RESULTS: Of 1780 articles
      reviewed, 1133 (63.7%) met inclusion criteria (manuscripts reporting human
      subjects, human tissue or identifiable personal data research), 36 (3.2%)
      articles lacked a statement of REB approval, 62 (5.5%) lacked disclosure of
      informed consent and 15 (1.3%) articles lacked both. Articles that did not state
      REB approval were associated with not stating informed consent (p<0.001). There
      were no editorial comments to alert readers to the lack of either REB approval or
      informed consent statements associated with any of the deficient articles.
      CONCLUSIONS: Articles that lack explicit statements of REB approval and informed
      consent are infrequent but continue to be published in major medical journals
      without editorial statements to alert the reader to this deficiency.

PMID- 18827112
TI  - Hopes for Helsinki: reconsidering "vulnerability".

PMID- 18827113
TI  - Can your patients reach you?

PMID- 18827114
TI  - Perfecting practice.

PMID- 18827115
TI  - Cesarean delivery for the second twin.
AB  - OBJECTIVE: To examine maternal and infant outcomes after a vaginal delivery of
      twin A and a cesarean delivery of twin B, and to identify whether the second twin
      experienced increased short-term morbidity as part of a combined route of
      delivery. METHODS: Between January 1, 1999, and December 31, 2000, a prospective
      cohort study of all cesarean deliveries was conducted at 13 university centers.
      This secondary analysis was limited to women with twin gestations who experienced
      labor and underwent cesarean delivery. We compared outcomes of the second twin in
      women who had vaginal delivery of the first twin and a cesarean delivery of the
      second twin to those who had cesarean delivery of both twins. RESULTS: One
      thousand twenty-eight twin pregnancies experienced labor and underwent cesarean
      delivery; 179 (17%) had a combined vaginal/cesarean delivery. Gestational age at
      delivery was 34.6 weeks in both groups (P=.97). The rupture of membranes to
      delivery interval was longer in the combined group (3.2 compared with 2.3 hours,
      P<.001). Endometritis and culture-proven sepsis in the second twin were more
      common in the combined group, respectively (n=24, odds ratio 1.6, 95% confidence
      interval, 1.0-2.7; n=15, odds ratio 1.8, 95% confidence interval, 1.0-3.4). These
      differences were not significant after logistic regression analysis. There were
      no statistically significant differences in an arterial cord pH of less than 7.0,
      Apgar score less than or equal to 3 at 5 minutes, seizures, grade III or IV
      intraventricular hemorrhage, hypoxic ischemic encephalopathy, or neonatal death.
      CONCLUSION: Combined twin delivery may be associated with endometritis and
      neonatal sepsis when compared with a twin delivery where both are delivered by
      cesarean in twin pregnancies experiencing labor. More serious neonatal sequelae,
      including hypoxic ischemic encephalopathy and death, were not affected by the
      route of delivery of the second twin.

PMID- 18827116
TI  - Placental characteristics in monochorionic twins with and without twin anemia
      polycythemia sequence.
AB  - OBJECTIVE: To study the placental angioarchitecture of monochorionic placentas
      with and without twin anemia-polycythemia sequence. METHODS: Eligible were all
      placentas from monochorionic twin gestations, not complicated by twin-to-twin
      transfusion syndrome and resulting in double survival. The study was conducted at
      two European Fetal Therapy Centers between 2002 and 2008. Placental
      angioarchitecture was evaluated using colored dye injection. Diagnosis of twin
      anemia-polycythemia sequence was based on the presence of large intertwin
      hemoglobin difference without the degree of amniotic fluid discordance that is
      required for the diagnosis of twin transfusion syndrome. RESULTS: Three-hundred
      thirteen monochorionic twin pregnancies were eligible for the study but placental
      data could not be completed for 62 placentas (20%). This left 251 monochorionic
      twin pregnancies of which 11 (4%) fulfilled the criteria for twin anemia
      polycythemia sequence. The median number of anastomoses in monochorionic
      placentas with and without twin anemia-polycythemia sequence was 3 (range: 2-5)
      and 7 (range: 0-25), respectively (P<.001). Small anastomoses were present in 91%
      (10/11) of twin anemia-polycythemia sequence-placentas compared with 5% (12/240)
      of cases without twin anemia-polycythemia sequence (P<.001). Arterioarterial
      anastomoses were absent in twin anemia-polycythemia sequence-placentas and
      present in 89% (213/240) of placentas without twin anemia-polycythemia sequence
      (P<.001). CONCLUSION: Monochorionic twin placentas with twin anemia-polycythemia
      sequence are characterized by a paucity of anastomoses and the absence of
      arterioarterial anastomoses. The few anastomoses that are present in twin anemia
      polycythemia sequence placentas are mostly small arteriovenous anastomoses.

PMID- 18827117
TI  - Accuracy of ultrasonographic fetal weight estimation in twin pregnancies.
AB  - OBJECTIVE: To compare the accuracy of fetal weight estimations between normal and
      growth-restricted twin and singleton pregnancies in a single tertiary center.
      METHODS: The computerized ultrasound database of a tertiary center was searched
      for all fetal weight estimations made in twin pregnancies from 2001 to 2006,
      which were performed up to 3 days before delivery. Accuracy was compared with a
      control group of singleton pregnancies at a 3:1 ratio. Estimated fetal weight was
      calculated by the Hadlock formula. Analyses were performed for the whole group
      and for pregnancies associated with fetal growth restriction and discordancy.
      RESULTS: The study groups included 278 twins and 834 singleton pregnancies. The
      twins group was characterized by a higher mean absolute percentage error compared
      with the singleton group (8.9% compared with 6.8%). Accuracy was lower for the
      second twins than for the first twins. When comparing the subgroup of fetal
      growth restriction, differences in sensitivity and specificity were small for
      singleton compared with overall twins (47.5% compared with 48.9% and 97.7%
      compared with 95.7%, respectively). Overall accuracy was better in the singleton
      group (95% compared with 88%), mainly due to relatively low accuracy in the
      second twin (86%). For detection of discordancy, estimated fetal weight had a
      sensitivity of 52%, specificity of 88%, and overall accuracy of 81%. CONCLUSION:
      The accuracy of the ultrasonographic estimated fetal weight seems to be lower for
      twin gestations than for singleton gestations, especially for second twins. These
      data should be considered by clinicians when making decisions based on
      ultrasonographic characteristics.

PMID- 18827118
TI  - Early fetal size and growth as predictors of adverse outcome.
AB  - OBJECTIVE: To evaluate the association between fetal size and growth between the
      first and second trimesters and subsequent adverse pregnancy outcome. METHODS: A
      cohort was created of 7,642 singleton pregnancies cared for in three obstetric
      units associated with Copenhagen University. Data were obtained from ultrasound
      measurements at 11-14 weeks (crown-rump length, biparietal diameter) and 17-21
      weeks (biparietal diameter). Fetal size was assessed by gestation-specific z
      scores, and fetal growth between the first and second trimester was calculated
      individually using conditional centiles. The main outcome measures were preterm
      delivery, smallness for gestational age, and perinatal death. RESULTS: Slow
      growth of the biparietal diameter less than the 10th and less than the 2.5th
      conditional centiles between first and second trimesters occurred in 10.4% and
      3.6% of the population, respectively. Biparietal diameter growth less than the
      10th centile was associated with perinatal death before 34 weeks (risk 0.5%
      compared with 0.04%, odds ratio [OR] 16.0, confidence interval [CI] 2.9-88.7).
      Biparietal diameter growth less than the 2.5th centile was the best predictor of
      perinatal death at any gestation, with a positive likelihood ratio of 4.7 and an
      OR of 7.3 (CI 2.4-22.2). In contrast, the biparietal diameter, dated by crown
      rump length, did not have an increased risk of perinatal death; however, there
      was a mildly increased risk of small for gestational age birth weight (less than
      the 10th customized centile) if the biparietal diameter was below the 10th
      centile in the first trimester (risk 17% compared with 12%, OR 1.5, CI 1.2-1.8)
      or in the second trimester (risk 15.8% compared with 12.4%, OR 1.3, CI 1.1-1.5).
      CONCLUSION: Slow growth of the fetal biparietal diameter between the first and
      second trimesters of pregnancy is a strong predictor of perinatal death before 34
      weeks.

PMID- 18827119
TI  - Treatment of acne using a 3-milligram drospirenone/20-microgram ethinyl estradiol
      oral contraceptive administered in a 24/4 regimen: a randomized controlled trial.
AB  - OBJECTIVE: To assess the efficacy of the combined oral contraceptive containing 3
      mg drospirenone/20-microgram ethinyl estradiol (3-mg drospirenone/20-microgram
      ethinyl estradiol) administered as 24 consecutive days of active treatment after
      a 4-day hormone-free interval (24/4 regimen) compared with placebo for the
      treatment of moderate acne vulgaris. METHODS: Healthy females aged 14-45 years
      with moderate acne were randomized in this double-blind study to 3-mg
      drospirenone/20-microgram ethinyl estradiol (n=270) or placebo (n=268) for six
      cycles of 28 days. The primary outcome measures of acne lesion counts and
      Investigator Static Global Assessment scale ratings were assessed at baseline and
      during cycles 1, 3, and 6. RESULTS: The percentage reduction from baseline to
      endpoint for total lesions is 46.3% for 3-mg drospirenone/20-microgram ethinyl
      estradiol 24/4 combination oral contraceptive group and 30.6% for placebo group
      (P<.001). The likelihood of participants in the 3-mg drospirenone/20-microgram
      ethinyl estradiol 24/4 regimen group having "clear" or "almost clear" skin as
      rated by the investigators at endpoint was about threefold (odds ratio 3.13, 95%
      confidence interval 1.69-5.81; P=.001) greater than in the placebo group. The 3
      mg drospirenone/20-microgram ethinyl estradiol 24/4 regimen was well tolerated.
      CONCLUSION: The low-dose combined oral contraceptive containing 3-mg
      drospirenone/20-microgram ethinyl estradiol administered in a 24/4 regimen
      significantly reduced acne lesion counts more effectively than placebo and
      demonstrated greater improvement in the Investigator Static Global Assessment
      rating of acne. The safety profile was consistent with low-dose combined oral
      contraceptive use.

PMID- 18827120
TI  - Real-world patterns of prescription refills for branded hormonal contraceptives:
      a reflection of contraceptive discontinuation.
AB  - OBJECTIVE: The objective was to describe timely refills of hormonal contraceptive
      products among a large, geographically diverse population of U.S. women as an
      estimate of method continuation over time. METHODS: Longitudinal prescription
      refills from the Verispan database were collected from 99% of retail pharmacies
      in the United States between October 2003 and August 2005 for specific branded
      hormonal contraceptives. We calculated refill rates for different contraceptive
      categories, for individual products, and for different age groups. RESULTS:
      Refill data were available for nearly 1.7 million women for 240 days and for
      almost 1 million women for 420 days. After 30 days, only 59.4-75.1% of women
      refilled their prescriptions for the various products on a timely basis. By 3
      months, only 47.7-61.2% of women returned for timely refills. By 12 months, only
      16.3-34.5% of women had consistently refilled their prescriptions. Very young
      women had refill rates for most methods that were at least as good as those of
      older women. CONCLUSION: These low rates of timely refill rates in actual
      practice indicate that few women had the potential for correct and consistent
      contraceptive use. New methods with extended cycles or a new progestin had higher
      rates than did other 28-day products. These high discontinuation rates suggest
      that barriers to successful utilization of contraceptives exist, and they
      highlight the need to routinely provide condoms and emergency contraception to
      women initiating hormonal contraception.

PMID- 18827121
TI  - Effects of depot medroxyprogesterone acetate and 20-microgram oral contraceptives
      on bone mineral density.
AB  - OBJECTIVE: Hormonal contraceptives may adversely affect bone mineral density.
      However, racial differences and the reversibility of these changes are poorly
      understood. This study measured bone mineral density changes during hormonal
      contraceptive use and after discontinuation in a triethnic population. METHODS:
      Bone mineral density was measured every 6 months for up to 3 years in 703 white,
      African-American, and Hispanic women using oral contraceptives (OCPs), depot
      medroxyprogesterone acetate (DMPA), or nonhormonal contraceptives, and in 68 DMPA
      discontinuers for up to 2 additional years. Mixed-model regression analyses were
      used to estimate the percentage change in bone mineral density for each
      contraceptive method. RESULTS: Over 3 years, DMPA and OCP users lost more bone
      mineral density than did nonhormonal contraceptive users (-3.7% and -0.5%
      compared with +1.9% at lumbar spine, and -5.2% and -1.3% compared with +0.6% at
      femoral neck, respectively). No differences were observed by race in bone mineral
      density changes that resulted from DMPA or OCP use. However, DMPA users aged 16
      24 years lost more bone mineral density at the spine (4.2% compared with 3.2%,
      P=.006) and femoral neck (6.0% compared with 4.2%, P=.001) than those aged 25-33
      years. After DMPA discontinuation, women who selected nonhormonal contraceptives
      gained bone mineral density (+4.9% at spine, +3.2% at femoral neck), whereas
      those who selected OCP recovered spinal (+2.3%) but not femoral neck bone mineral
      density (-0.7%). CONCLUSION: Use of very-low-dose OCPs may result in a small
      amount of bone loss. Use of DMPA results in greater bone loss, but this is
      largely reversible at the spine. Use of very-low-dose OCPs after DMPA
      discontinuation may slow bone recovery.

PMID- 18827122
TI  - Misoprostol vaginal insert compared with dinoprostone vaginal insert: a
      randomized controlled trial.
AB  - OBJECTIVE: To compare the 50-microgram (misoprostol vaginal insert 50) and 100
      microgram (misoprostol vaginal insert 100) dose reservoirs of the misoprostol
      vaginal insert to 10-mg dinoprostone vaginal insert for time to vaginal delivery
      and rate of cesarean delivery. METHODS: A total of 1,308 women requiring cervical
      ripening (modified Bishop score less than or equal to 4) before induction of
      labor were randomly assigned to receive misoprostol vaginal insert 100 (n=428),
      misoprostol vaginal insert 50 (n=443) or 10-mg dinoprostone vaginal insert
      (n=436). The primary outcomes were time to vaginal delivery and rate of cesarean
      births. Safety was also assessed by comparing frequency of adverse events.
      RESULTS: Median time to vaginal delivery was 1,596, 2,127, and 1,650 minutes for
      misoprostol vaginal insert 100, misoprostol vaginal insert 50, and dinoprostone
      vaginal insert, respectively (P=.97 and 0.01 compared with dinoprostone vaginal
      insert, respectively). Of those who delivered in first admission, cesarean
      deliveries occurred in 119 of 421 (28.3%), 124 of 429 (28.9%), and 115 of 424
      (27.1%) of participants treated with misoprostol vaginal insert 100, misoprostol
      vaginal insert 50, and dinoprostone vaginal inserts, respectively (relative risk
      1.04, 95% confidence interval 0.84-1.30 for misoprostol vaginal insert 100 and
      relative risk 1.06, 95% confidence interval 0.86-1.32 for misoprostol vaginal
      insert 50 compared with dinoprostone vaginal insert). Medication-related adverse
      events included hyperstimulation syndrome in 17 of 428 (4.0%), 6 of 443 (1.4%),
      and 21 of 436 (4.8%); and nonreassuring fetal heart rate patterns in 63 of 428
      (14.7%), 54 of 443 (12.2%), and 67 of 436 (15.4%) of participants treated with
      the misoprostol vaginal insert 100, misoprostol vaginal insert 50, and
      dinoprostone vaginal inserts, respectively. CONCLUSION: The misoprostol vaginal
      insert 100 and the dinoprostone vaginal insert had similar median time intervals
      to vaginal delivery, whereas the misoprostol vaginal insert 50 had a
      significantly longer time to vaginal delivery. The three products had similar
      cesarean rates and safety profiles.

PMID- 18827123
TI  - Evaluating the rate and risk factors for fetal loss after chorionic villus
      sampling.
AB  - OBJECTIVE: To estimate the fetal loss rate in our center and evaluate the risk
      factors associated with such losses after chorionic villus sampling (CVS).
      METHODS: This is a retrospective cohort study including all women undergoing
      chorionic villus sampling and a control group that had no invasive procedure at a
      single center over a 16-year period. Fetal loss was defined as any loss before 24
      weeks of gestation. Univariable and multiple logistic regression analyses were
      used to compare pregnancies resulting in fetal loss to those without a loss and
      to adjust for potential confounders between the groups. RESULTS: Of 5,243 women
      who had CVS who were compared with 4,917 women seen before 14 weeks who had no
      invasive procedure, there were 138 (2.7%) fetal losses before 24 weeks of
      gestation in the CVS group compared with 161 (3.3%) in the control group
      (relative risk 0.80, 95% confidence interval, 0.64-1.0). The difference in loss
      rate of -0.7% (95% confidence interval, -0.02 to 1.3) between the CVS group and
      those who had no procedure was not statistically significant at P<.05. The
      significant risk factors for fetal loss were African-American maternal race, at
      least two aspirations/needle insertions, heavy bleeding during CVS, maternal age
      younger than 25 years, and gestational age at performing CVS before 10 weeks.
      CONCLUSION: The estimated fetal loss rate after CVS was not significantly
      different from the group that had no procedure. Significant predictors of fetal
      loss after CVS were identified, but the accuracy of the final model for
      predicting fetal loss was only modest.

PMID- 18827124
TI  - Eclampsia in the Netherlands.
AB  - OBJECTIVE: The incidence of maternal mortality due to hypertensive disorders of
      pregnancy in the Netherlands is greater than in other Western countries. We aimed
      to confirm and explain this difference by assessing incidence, risk factors, and
      substandard care of eclampsia in the Netherlands. METHODS: In a nationwide
      population-based cohort study, all cases of eclampsia were prospectively
      collected during a 2-year period (2004-2006). All pregnant women in the
      Netherlands in the same period acted as reference cohort (n=371,021). Substandard
      care was assessed in all cases. A selection of cases was extensively audited by
      an expert panel. Main outcome measures were incidence, case fatality rate,
      possible risk factors, and substandard care. RESULTS: All 98 Dutch maternity
      units participated (100%). There were 222 cases of eclampsia, for an incidence of
      6.2 per 10,000 deliveries. Three maternal deaths occurred; the case fatality rate
      was 1 in 74. Risk factors in univariable analysis included multiple pregnancy,
      primiparity, young age, ethnicity, and overweight. Prophylactic magnesium sulfate
      was given in 10.4% of women, and antihypertensive medication was given in 39.6%
      of women with a blood pressure on admission at or above 170/110 mm Hg.
      Additionally, substandard care was judged to be present by an expert panel in 15
      of 18 audited cases (83%). CONCLUSION: The incidence of eclampsia in the
      Netherlands is markedly increased as compared with other Western European
      countries. Substandard care was identified in many cases, indicating the need for
      critical evaluation of the management of hypertensive disease in the Netherlands.

PMID- 18827125
TI  - Maternal congenital cardiac disease: outcomes of pregnancy in a single tertiary
      care center.
AB  - OBJECTIVE: To evaluate contemporary perinatal and cardiac outcomes of pregnancies
      in women with major structural congenital heart disease. METHODS: Obstetric,
      neonatal, and cardiac outcomes were abstracted retrospectively from medical
      records of all women with congenital cardiac disease delivering at our
      institution from 2000-2007 and compared by type of structural defect. Predictors
      of adverse cardiac or obstetric events were identified. RESULTS: Over the 7-year
      study period, 74 deliveries occurred in 69 women with congenital heart disease,
      median age 28 years. There were three right-obstructive defects, 14 left
      obstructive defects, four right-regurgitant defects, 19 conotruncal defects, 19
      shunts, and four miscellaneous lesions. There were 21 adverse cardiac events in
      15 pregnancies (20.2%); these were defined as maternal death, congestive heart
      failure, myocardial infarction, stroke, the need for urgent cardiac intervention,
      or arrhythmia requiring treatment. There were 44 adverse obstetric events in 34
      pregnancies (45.9%), defined as preterm delivery, stillbirth, preeclampsia, small
      for gestational age, or neonatal intensive care unit admission. Patients with
      shunt morphology were more likely to experience adverse obstetric and cardiac
      outcomes. CONCLUSION: Pregnancy in women with underlying major congenital heart
      defects poses increased risks to both mother and fetus. Nonetheless, favorable
      maternal and neonatal outcomes occur in the majority of patients.

PMID- 18827126
TI  - Limited public knowledge of obesity and endometrial cancer risk: what women know.
AB  - OBJECTIVE: To estimate if women in the general population are aware of the
      relationship between obesity and cancer risk, and to identify groups who may
      benefit from educational programs. METHODS: A self-administered survey was
      distributed to women in the Houston community. The questions were taken from a
      bank of validated questions published by the Center for Disease Control,
      Behavioral Risk Factor Surveillance System, and the Harvard Forums on Health
      Survey. Demographic information and participant knowledge of obesity-related
      cancer risk was collected. Logistic regression and Cochran-Armitage tests for
      trend were use to assess the association between predictor variables and
      knowledge. RESULTS: One thousand five hundred forty-five women completed the
      survey; 28% were normal weight (body mass index [BMI] less than 25 kg/m(2)), 24%
      were overweight (BMI 25-30 kg/m(2)), and 45% were obese (BMI at least 30
      kg/m(2)). Fifty-eight percent (95% confidence interval 56-61%) were not aware
      that obesity increased risk for endometrial cancer. There was no difference in
      knowledge of endometrial cancer risk associated with any of the demographic
      characteristics studied. Black women were the most likely to respond that they
      did not know about the relationship between obesity and cancer. There was no
      association between personal weight and knowledge of obesity-associated risk.
      CONCLUSION: There is limited knowledge of the relationship between obesity and
      cancer risk, particularly among black women. Patient education regarding these
      risks may increase awareness of the relationship between obesity and endometrial
      cancer among women.

PMID- 18827127
TI  - Levels of circulating cell-free nuclear and mitochondrial DNA in benign and
      malignant ovarian tumors.
AB  - OBJECTIVE: To analyze the levels of circulating cell-free nuclear DNA and
      circulating cell-free mitochondrial DNA in patients with benign and malignant
      ovarian tumors using a gold-standard assay and to investigate whether
      quantitative alterations of the circulating cell-free species have values in the
      management of the patients. METHODS: One hundred four patients were recruited for
      this study. We developed a quantitative, multiplex polymerase chain reaction to
      measure the levels of circulating cell-free nuclear DNA and circulating cell-free
      mitochondrial DNA in serum and plasma of patients with epithelial ovarian cancer,
      benign epithelial ovarian tumors, or endometriosis. The levels of the circulating
      cell-free DNA were compared with those of a healthy, age-matched control group.
      RESULTS: The patients with epithelial ovarian cancer had significantly higher
      amounts of circulating cell-free nuclear DNA and circulating cell-free
      mitochondrial DNA in plasma compared with the healthy control group (mean of
      nuclear DNA 10,723/2,591 and mean of mitochondrial DNA 4,918,978/2,294,264,
      P=.009 and 0.022, respectively) and with the other group with benign ovarian
      diseases (mean of nuclear DNA 10,723/2,965 and mean of mitochondrial DNA
      4,918,978/1,597,551, P=.027 and 0.002, respectively). However, no relationship
      between levels of the circulating cell-free DNA and the pathological parameters
      as well as CA 125 measurement in patients with epithelial ovarian cancer was
      found. A significant difference between the epithelial ovarian cancer and
      endometriosis group was found in circulating cell-free mitochondrial DNA but not
      in circulating cell-free nuclear DNA (mean of mitochondrial DNA
      4,918,978/2,273,988 and mean of nuclear DNA 10,723/3,291, P=.013 and 0.105,
      respectively). CONCLUSION: Elevated levels of circulating cell-free nuclear DNA
      and circulating cell-free mitochondrial DNA in epithelial ovarian cancer may have
      diagnostic value. Our finding suggests that the circulating molecules might be
      potential biomarkers in the disease.

PMID- 18827128
TI  - Symptoms and pelvic support defects in specific compartments.
AB  - OBJECTIVE: To investigate whether the nature of the anatomic defects in pelvic
      organ prolapse (POP) correlates with the character of the symptoms. METHODS: This
      study was a cross-sectional investigation within a population-based sample. Two
      hundred eighty women who had completed a symptom questionnaire were examined
      according to POP quantification by two gynecologists blinded to symptom reports.
      RESULTS: An age- and parity-adjusted logistic regression model, controlling for
      POP in other compartments, revealed that the feeling of vaginal bulge was
      specific to prolapse but not to any particular compartment, although the
      association was strongest with anterior-wall prolapse (odds ratio [OR] for the
      symptom among women with stage II-IV relative to stage 0 was 5.8, 95% confidence
      interval [CI] 2.5-13.3). Urge urinary incontinence tended to be linked to POP in
      either the anterior or posterior wall, but the association was stronger with
      anterior-wall prolapse. Stress urinary incontinence was strongly linked to
      posterior-wall prolapse (stage II-IV OR 5.4, 95% CI 1.9-15.2). Self-reports of
      hard/lumpy stool and difficult or painful defecation tended to be associated with
      anterior-wall prolapse but without consistent relationships with stage. Painful
      defecation was the only bowel symptom significantly linked to posterior-wall
      prolapse (P=.05). CONCLUSION: Pelvic floor-related symptoms do not predict the
      anatomic location of the prolapse in women with mild to moderate prolapse.

PMID- 18827130
TI  - Postpartum screening for diabetes after a gestational diabetes mellitus-affected
      pregnancy.
AB  - OBJECTIVE: To estimate trends in postpartum glucose testing in a cohort of women
      with gestational diabetes mellitus (GDM). METHODS: A validated computerized
      algorithm using Kaiser Permanente Northwest automated data systems identified
      36,251 live births or stillbirths from 1999 through 2006. The annual percentage
      of pregnancies complicated by gestational diabetes with clinician orders for and
      completion of a fasting plasma glucose (FPG) test within 3 months of delivery was
      calculated. Logistic regression with generalized estimating equations was used to
      test for statistically significant trends. RESULTS: The percentages of
      pregnancies affected by GDM increased from 2.9% in 1999 to 3.6% in 2006 (P<.01).
      Clinician orders for postpartum tests increased from 15.9% in 1999 to 79.3% in
      2004 (P<.01), and then remained stable through 2006. Completed FPG tests
      increased from 9.0% in 1999 to 57.8% in 2004 (P<.01), and then remained stable
      through 2006. No oral glucose tolerance tests were ordered. From 2004 to 2006,
      the practice site where women received care was the factor most strongly
      associated with the clinician order, but it was not predictive of test
      completion. Among women with clinician orders, those who were Asian or Hispanic
      or who attended the 6-week postpartum examination were more likely to complete
      the test than their counterparts. CONCLUSION: Postpartum glucose testing in women
      with GDM-affected pregnancies increased over time. However, even in recent years,
      42% of women with GDM-affected pregnancies failed to have a postpartum FPG test,
      and no test was ordered for 21% of GDM-affected pregnancies.

PMID- 18827129
TI  - Nicotine gum for pregnant smokers: a randomized controlled trial.
AB  - OBJECTIVE: To estimate the safety and efficacy of treatment with 2-mg nicotine
      gum for smoking cessation during pregnancy. METHODS: Pregnant women who smoked
      daily received individualized behavioral counseling and random assignment to a 6
      week treatment with 2-mg nicotine gum or placebo followed by a 6-week taper
      period. Women who did not quit smoking were instructed to reduce the number of
      cigarettes smoked by substituting with gum. Measures of tobacco exposure were
      obtained throughout the study. RESULTS: Participants in the nicotine (n = 100)
      and placebo (n = 94) groups were comparable in age, race/ethnicity, and smoking
      history. Biochemically validated smoking-cessation rates were not significantly
      higher with nicotine gum compared with placebo (after 6 weeks of treatment: 13%
      compared with 9.6%, P=.45; at 32-34 weeks of gestation: 18% compared with 14.9%,
      P=.56). Using a completer analysis, nicotine gum significantly reduced the number
      of cigarettes smoked per day (nicotine gum: -5.7 [standard deviation (SD)=6.0];
      placebo: -3.5 [SD=5.7], P=.035), and cotinine concentration (nicotine gum: -249
      ng/mL [SD=397]; placebo: -112 ng/mL [SD=333]; P=.04). Birth weights were
      significantly greater with nicotine gum compared with placebo (3,287 g [SD=566]
      and 2,950 g [SD=653], respectively, P<.001). Gestational age was also greater
      with nicotine-replacement therapy than with placebo (38.9 weeks [SD=1.7] and 38.0
      weeks [SD=3.3], respectively; P=.014). CONCLUSION: Although nicotine gum did not
      increase quit rates, use of nicotine gum increased birth weight and gestational
      age, two key parameters in predicting neonatal wellbeing.

PMID- 18827131
TI  - Cardiovascular disease risk profiles in women with histories of gestational
      diabetes but without current diabetes.
AB  - OBJECTIVE: To compare the cardiovascular disease risk factor profiles of parous
      women with a history of gestational diabetes who had not developed diabetes,
      parous women with diagnosed diabetes, and parous women with neither condition.
      METHODS: We conducted cross-sectional analyses of 4,631 parous women who were not
      currently pregnant in the Third National Health and Nutrition Examination Survey
      (1988-1994). Women were classified by self-report as having a history of
      gestational diabetes who were not currently diabetic (n=85), diagnosed diabetics
      (n=218), or as having neither condition (n=4,328). We compared these groups with
      respect to cholesterol subtypes, blood pressure, uric acid, microalbuminuria,
      insulin, glucose, and clustering of risk factors, before and after adjustment for
      demographic and behavioral factors and central obesity. RESULTS: In unadjusted
      comparisons, women who had a history of gestational diabetes who were not
      currently diabetics had a more favorable or similar risk factor profile compared
      with unaffected women, with two exceptions: greater levels of mean fasting
      glucose (94.0 mg/dL compared with 106.8 mg/dL, P<.001) and mean fasting insulin
      (10.2 international units/L compared with 14.0 international units/L, P<.001).
      These patterns were attenuated after adjustment for demographic factors and waist
      circumference, but remained significant for fasting glucose and the ratio of
      urine microalbumin/creatinine. Parous women with diagnosed diabetes had
      significantly worse cardiovascular disease risk profiles than unaffected women
      before and after adjustment. CONCLUSION: Women who had a history of gestational
      diabetes who were not currently diabetics have a similar cardiovascular disease
      risk profile to unaffected women, with the exception of insulin and glucose
      levels.

PMID- 18827132
TI  - Anti-factor Xa plasma levels in pregnant women receiving low molecular weight
      heparin thromboprophylaxis.
AB  - OBJECTIVE: To report the incidence of prophylactic, subprophylactic, and
      supraprophylactic anti-factor Xa activity in pregnant patients receiving low
      molecular weight heparin for venous thromboembolism prophylaxis, and to evaluate
      whether maternal weight, body mass index, age, gestational age, or the low
      molecular weight heparin dose correlated with anti-factor Xa levels. METHODS: We
      reviewed 321 anti-factor Xa levels in 77 patients from one Maternal-Fetal
      Medicine faculty practice. All patients were administered low molecular weight
      heparin that subsequently was adjusted based upon serial assessment of peak
      plasma (at 4 hours postinjection) anti-factor Xa levels at less than 36 weeks
      gestation. Targeted prophylactic range of peak plasma anti-factor Xa level was
      0.2-0.4 units/mL. RESULTS: Only 59% of anti-Xa concentrations were in the
      prophylactic range, whereas 26% were subprophylactic, and 15% were
      supraprophylactic. Anti-Xa values were not significantly more likely to be
      prophylactic in early compared with late pregnancy, obese compared with nonobese
      patients, or in patients receiving a weight-based minimal dose compared with
      patients receiving less than a weight-based minimal dose. Anti-factor Xa levels
      did not correlate with maternal age, weight, body mass index, or gestational age,
      but there was a positive correlation with the percent of the minimal weight-based
      dose. CONCLUSION: Even with enhanced low molecular weight heparin dosing, 26% of
      patients have subprophylactic anti-factor Xa levels. Serial anti-factor Xa
      assessment for dose adjustment should be considered for all pregnant women
      receiving low molecular weight heparin.

PMID- 18827133
TI  - Low rates of both asymptomatic chlamydia screening and diagnostic testing of
      women in US outpatient clinics.
AB  - OBJECTIVE: To estimate demographic characteristics of nonpregnant women who seek
      health care in hospital outpatient clinics, and the proportion of visits where a
      chlamydia test was not done in asymptomatic young women at preventive visits and
      in symptomatic women. METHODS: We analyzed data from the 2005 National Hospital
      Ambulatory Medical Care Survey to estimate the number of visits made by
      nonpregnant women aged 15-25 years and 26-35 years. We estimated the proportion
      of preventive visits where young women were not screened for chlamydia and the
      proportion of visits where women with signs or symptoms of chlamydia were not
      tested. RESULTS: In 2005, 5.2 million visits were made by nonpregnant women aged
      15-25 years to outpatient clinics: 21.3% were by black non-Hispanic women, 15.2%
      by Hispanic women, 41.9% by women with Medicaid/State Children's Health Insurance
      Program insurance, and 10.8% by women with signs or symptoms of chlamydia. These
      young women were not screened at 84.0% of 1.2 million asymptomatic preventive
      visits, and were not tested for chlamydia at 78.3% of 0.6 million visits where
      they presented with signs or symptoms of chlamydia. Women aged 26-35 years were
      not tested at 86.3% of 0.4 million visits where they presented with signs or
      symptoms of chlamydia. CONCLUSION: While low chlamydia screening coverage has
      been reported, the low level of diagnostic testing in outpatient clinics was
      unexpected. Simple and effective interventions are needed to increase both
      diagnostic testing and screening of young women for Chlamydia in outpatient
      clinics, a venue that provides care to at-risk populations.

PMID- 18827134
TI  - Radical hysterectomy in obese and morbidly obese women with cervical cancer.
AB  - OBJECTIVE: To compare intraoperative and postoperative outcomes, pathologic
      findings, cancer recurrence, and death rates in normal-weight, overweight, obese,
      and morbidly obese women undergoing radical hysterectomy and pelvic
      lymphadenectomy for early-stage cervical cancer. METHODS: A review of patients
      who underwent radical hysterectomy and pelvic lymphadenectomy for invasive
      cervical cancer between 1990 and 2006 was performed. On the basis of body mass
      index (BMI) (calculated as weight [kg]/[height (m)](2)), women were categorized
      as normal weight (BMI 18.5-24.9), overweight (BMI 25.0-29.9), obese (BMI 30.0
      34.9), or morbidly obese (BMI at least 35.0). RESULTS: Four hundred eight women
      met the inclusion criteria. Of these, 155 (38%) were normal weight, 126 (31%)
      were overweight, 77 (19%) were obese, and 50 (12%) were morbidly obese. There
      were no statistically significant differences between these four groups in age,
      Charlson comorbidity score, smoking history, stage, histologic grade or subtype,
      tumor size, depth of invasion, transfusion rate, operative time, or
      intraoperative complications. Higher BMI was significantly correlated with higher
      estimated operative blood loss (P=.001). There were no statistically significant
      differences between the groups in pathologic findings, length of postoperative
      hospital stay, postoperative complications, readmission rate, or proportion of
      women receiving adjuvant radiotherapy. At a median follow-up time of 64 months,
      there were no differences between groups in rates of recurrence or death from
      disease. CONCLUSION: Radical hysterectomy and pelvic lymphadenectomy is feasible
      for obese and morbidly obese women with cervical cancer. Obesity alone should not
      be a contraindication to radical hysterectomy in women with cervical cancer.

PMID- 18827135
TI  - Observations from 450 shoulder dystocia simulations: lessons for skills training.
AB  - Poor neonatal outcomes after shoulder dystocia have been associated with
      inappropriate management. Until there are significant developments in the
      prediction and subsequent prevention of shoulder dystocia, improving shoulder
      dystocia management through practical training may be the most effective method
      of reducing the associated morbidity and mortality. Four hundred fifty simulated
      shoulder dystocia scenarios, managed by 95 midwives and 45 doctors from six U.K.
      hospitals during the course of 1 year, were video recorded during a study of
      obstetric emergency training. Analysis of recorded data revealed that, before
      training, 57% were unable to deliver the baby, almost two thirds failed to call
      for pediatric support, and 1 in 27 used fundal pressure. Recurring difficulties
      in management were observed: poor communication, inability to gain internal
      access, confusion over internal maneuvers, and the application of excessive
      traction. Significant improvements in management were observed after training and
      persisted up to 1 year after training. The lessons learned from this study can
      inform and improve future training and management. This article describes
      difficulties encountered by the participants and discusses how training may be
      focused to address these problems.

PMID- 18827136
TI  - Mode of delivery: toward responsible inclusion of patient preferences.
AB  - Deciding when and how to incorporate patient preferences regarding mode of
      delivery is challenging for both obstetric providers and policymakers. An
      analysis of current guidelines in four clinical scenarios (prior cesarean, twin
      delivery, breech presentation, and maternal request for cesarean) indicates that
      some guidelines are highly prescriptive whereas others are more flexible, based
      on physicians' discretion or (less frequently) patient preferences, without
      consistency or explicit rationale for when such flexibility is permissible,
      advisable, or obligatory. Although patient-choice advocates have called for more
      patient-responsive guidelines, concerns also have been raised, especially in the
      context of discussions of cesarean delivery on maternal request, about the
      dangers of unfettered patient-preference-driven clinical decisions. In this
      article, we outline a framework for the responsible inclusion of patient
      preferences into decision making regarding approach to delivery. We conclude,
      using this framework, that more explicit incorporation of patient preferences is
      called for in the first three scenarios and indicate why expanding access to
      cesarean delivery on maternal request is more complicated and would require more
      data and further consideration.

PMID- 18827137
TI  - Pregnancy after solid organ transplantation.
AB  - For women with end-stage organ failure, transplantation is an established
      therapeutic option. Pregnancy after solid organ transplantation is no longer
      uncommon, especially with the recent advances in transplantation surgery and the
      availability of newer immunosuppressants. This article will review
      preconceptional counseling, common pregnancy complications, prenatal and
      intrapartum considerations, outcome by organ, immunosuppressant therapies, and
      neonatal outcomes based on data available from case series and voluntary
      registries. Some recommendations are provided to assist in the management of
      pregnancies after solid organ transplantation.

PMID- 18827138
TI  - Nonmenstrual toxic shock syndrome due to methicillin-resistant Staphylococcus
      aureus.

PMID- 18827139
TI  - Effect of prolonged vaginal distention and sphincter transection on physiologic
      function of the external anal sphincter in an animal model.

PMID- 18827140
TI  - Lynch syndrome in women less than 50 years of age with endometrial cancer.

PMID- 18827142
TI  - ACOG Practice Bulletin, clinical management guidelines for obstetrician
      gynecologists number 98, October 2008 (replaces Practice Bulletin number 58,
      December 2004). Ultrasonography in pregnancy.

PMID- 18827143
TI  - ACOG Committee Opinion number 419 October 2008 (replaces no. 291, November 2003).
      Use of progesterone to reduce preterm birth.

PMID- 18827144
TI  - All the King's horses and all the King's men: maybe physiology can put Humpty
      Dumpty back together again.

PMID- 18827145
TI  - Endothelial dysfunction starting in utero: you are what your mother eats?

PMID- 18827146
TI  - To be or not to be ... hypertensive: that is the question.

PMID- 18827147
TI  - Raising the volume on near-silent epithelial Na+ channels.

PMID- 18827148
TI  - Evaluation of guidelines for community-acquired pneumonia: a story of
      confounders, surprises and challenges.

PMID- 18827149
TI  - Alveolar permeability and stretch: too far, too fast.

PMID- 18827150
TI  - Lung function decline in COPD trials: bias from regression to the mean.

PMID- 18827151
TI  - A dichotomy in bronchiolitis obliterans syndrome after lung transplantation
      revealed by azithromycin therapy.
AB  - Bronchiolitis obliterans syndrome (BOS) is the most important cause of late
      mortality following lung transplantation, resulting in major morbidity and a huge
      burden on healthcare resources. Treatment options are limited, resulting in a
      mere stabilisation of the lung function decline. Recent introduction of the
      macrolide antibiotic azithromycin raised new hope after demonstrating lung
      function improvement in subsets of patients. The present study aimed to provide
      an overview of the clinical effects on azithromycin in the setting of BOS after
      lung transplantation, with special emphasis on the anti-inflammatory actions.
      Moreover, the authors proposed a new frame of thinking centred on a dichotomy in
      the pathogenesis and clinical phenotype of BOS. Subsets of BOS patients were
      identified who do or do not respond to azithromycin (regarding forced expiratory
      volume in one second (FEV(1)), bronchoalveolar lavage (BAL)
      neutrophilia/interleukin-8). These observations have shed new light on the
      current belief that BOS represents a homogenous clinical entity in which the
      neutrophil is the main culprit. Recent clinical observations, supported by
      research findings, have revealed a dichotomy in the clinical spectrum of BOS with
      neutrophilic (partially) reversible allograft dysfunction (responding to
      azithromycin) and fibroproliferative BOS (not responding to azithromycin). This
      concept is reinforced by unique data obtained in BOS patients, consisting of
      histology specimens, physical and radiological examination, FEV(1 )and BAL
      examination. The acceptance of this dichotomy can improve understanding of the
      heterogeneous pathological condition that constitutes bronchiolitis obliterans
      syndrome, thus encouraging a more accurate diagnosis and, ultimately, better
      tailored treatment for each bronchiolitis obliterans syndrome patient.

PMID- 18827152
TI  - COPD-related morbidity and mortality after smoking cessation: status of the
      evidence.
AB  - The evidence base for the benefit of quitting smoking as regards morbidity and
      mortality outcomes in patients with moderate-to-severe chronic obstructive
      pulmonary disease (COPD) is limited. The present article is a review of the
      existing literature. A systematic literature search in medical databases was
      performed until March 2006, and subsequently until September 1, 2007. The
      outcomes examined were COPD-related morbidity and mortality (including all-cause
      mortality) in COPD patients in connection with smoking cessation. A total of 21
      and 27 published articles on morbidity and mortality, respectively, were
      identified and reviewed. For both outcomes, only a few of the studies included
      patients with severe COPD. Most of the studies reported a beneficial effect of
      smoking cessation compared with continued smoking, whereas a few found no
      improvement. Methodological problems, including small study sizes, poor data
      quality, possibility of reverse causality and incomplete ascertainment of cause
      of death, limit interpretation of some of the studies. The evidence as a whole
      supports the conclusion that, even in severe chronic obstructive pulmonary
      disease, smoking cessation slows the accelerated rate of lung function decline
      and improves survival compared with continued smoking.

PMID- 18827153
TI  - Epidermal growth factor receptor-mediated innate immune responses and their roles
      in airway diseases.
AB  - Inhaled air is contaminated with pathogens and particulates that may deposit in
      the airways and damage the host. In response to these invaders, the airway
      epithelium has developed innate immune responses that provide a defence against
      the invaders and protect the airway structure and function. Thus, the epithelium
      of conducting airways becomes the "battleground" between the invaders and the
      host. Recent evidence suggests that airway epithelial surface signalling through
      the epidermal growth factor receptor (EGFR) is a convergent pathway producing
      innate immune responses to a variety of infectious and noninfectious noxious
      stimuli. In the present review, the EGFR signalling pathways leading to airway
      mucin production, neutrophil recruitment (via interleukin-8 production) and
      airway epithelial repair were examined. The importance of these findings in human
      airway diseases was also investigated. The current authors suggest that the
      exaggerated innate immune responses found in chronic inflammatory airway diseases
      (e.g. chronic obstructive pulmonary disease, cystic fibrosis and severe asthma)
      contribute to the pathogenesis or the aggravation of these diseases. Potential
      therapies include inhibition of the various elements of the described epidermal
      growth factor receptor cascade. In considering each therapeutic intervention, the
      potential benefits must be considered in relation to potential deleterious
      effects.

PMID- 18827154
TI  - Intermittent hypoxia and sleep-disordered breathing: current concepts and
      perspectives.
AB  - There are three major types of sleep-disordered breathing (SDB) with respect to
      prevalence and health consequences, i.e. obstructive sleep apnoea syndrome
      (OSAS), Cheyne-Stokes respiration and central sleep apnoea (CSR-CSA) in chronic
      heart failure, and obesity hypoventilation syndrome (OHS). In all three
      conditions, hypoxia appears to affect body functioning in different ways. Most of
      the molecular and cellular mechanisms that occur in response to SDB-related
      hypoxia remain unknown. In OSAS, an inflammatory cascade mainly dependent upon
      intermittent hypoxia has been described. There is a strong interaction between
      haemodynamic and inflammatory changes in promoting vascular remodelling.
      Moreover, during OSAS, most organ, tissue or functional impairment is related to
      the severity of nocturnal hypoxia. CSR-CSA occurring during heart failure is
      primarily a consequence of cardiac impairment. CSR-CSA has deleterious
      consequences for cardiac prognosis and mortality since it favours sympathetic
      activation, ventricular ectopy and atrial fibrillation. Although correction of
      CSR-CSA seems to be critical, there is a need to establish therapy guidelines in
      large randomised controlled trials. Finally, OHS is a growing health concern,
      owing to the worldwide obesity epidemic and OHS morbidities. The pathophysiology
      of OHS remains largely unknown. However, resistance to leptin, obesity and severe
      nocturnal hypoxia lead to insulin resistance and endothelial dysfunction. In
      addition, several adipokines may be triggered by hypoxia and explain, at least in
      part, OHS morbidity and mortality. Overall, chronic intermittent hypoxia appears
      to have specific genomic effects that differ notably from continuous hypoxia.
      Further research is required to fully elucidate the molecular and cellular
      mechanisms.

PMID- 18827155
TI  - Definition, assessment and treatment of wheezing disorders in preschool children:
      an evidence-based approach.
AB  - There is poor agreement on definitions of different phenotypes of preschool
      wheezing disorders. The present Task Force proposes to use the terms episodic
      (viral) wheeze to describe children who wheeze intermittently and are well
      between episodes, and multiple-trigger wheeze for children who wheeze both during
      and outside discrete episodes. Investigations are only needed when in doubt about
      the diagnosis. Based on the limited evidence available, inhaled short-acting
      beta(2)-agonists by metered-dose inhaler/spacer combination are recommended for
      symptomatic relief. Educating parents regarding causative factors and treatment
      is useful. Exposure to tobacco smoke should be avoided; allergen avoidance may be
      considered when sensitisation has been established. Maintenance treatment with
      inhaled corticosteroids is recommended for multiple-trigger wheeze; benefits are
      often small. Montelukast is recommended for the treatment of episodic (viral)
      wheeze and can be started when symptoms of a viral cold develop. Given the large
      overlap in phenotypes, and the fact that patients can move from one phenotype to
      another, inhaled corticosteroids and montelukast may be considered on a trial
      basis in almost any preschool child with recurrent wheeze, but should be
      discontinued if there is no clear clinical benefit. Large well-designed
      randomised controlled trials with clear descriptions of patients are needed to
      improve the present recommendations on the treatment of these common syndromes.

PMID- 18827156
TI  - Occupational asthma caused by Arabidopsis thaliana: a case of laboratory plant
      allergy.
AB  - A 36-yr-old male never-smoker with an 8-yr history of hay fever but no past
      history of asthma undertook a 3-yr research project involving the plant
      Arabidopsis thaliana. The subject was based in a small laboratory with an
      attached growing room. After 30 months of research, he began to develop
      breathlessness within 5-10 min of entering the laboratory. Initial investigations
      confirmed asthma with airflow obstruction (forced expiratory volume in one second
      (FEV(1))/forced vital capacity was 3.01/4.75 L; predicted values were 3.67/4.43
      L) and increased airway responsiveness. Serial peak expiratory flow measurements
      showed a work-related pattern. A supervised workplace challenge test led to a
      fall in FEV(1) from the baseline value of 3.10 L to 1.95 L within 20 min of
      entering the growing room. Skin-prick solutions were prepared from Arabidopsis
      leaves and flower heads; positive 4-mm responses were obtained to the flower
      heads (i.e. to the pollen). Arabidopsis is a member of the Brassicaceae family.
      It is used extensively in plant biology research as its genome is small, has been
      fully sequenced and is easily manipulated. The present article represents the
      first reported case of occupational asthma due to Arabidopsis thaliana.

PMID- 18827157
TI  - Lung hyperinflation: foe or friend?
AB  - Breath-hold divers employ glossopharyngeal insufflation (GI) in order to prevent
      the lungs from compressing at great depth and to increase intrapulmonary oxygen
      stores, thus increasing breath-hold time. The presented case study shows the
      physiological data and dynamic magnetic resonance imaging (dMRI) findings of
      acute hyperinflation, deliberately induced by GI, in a breath-hold diver and
      discusses the current state of knowledge regarding the associated hazards of this
      unique competitive sport. Static and dynamic lung volumes and expiratory flows
      were within the normal range, with vital capacity and peak expiratory flow being
      higher than the predicted values. Airway resistance and diffusing capacity of the
      lung for carbon monoxide were normal. Static compliance was normal and increased
      five-fold with hyperinflation. dMRI revealed a preserved shape of the thorax and
      diaphragm with hyperinflation. A herniation of the lung beneath the sternum and
      enlargement of the costodiaphragmatic angle were additional findings during the
      GI manoeuvre. After expiration, complete resolution to baseline was demonstrated.
      Hyperinflation can be physiological and even protective under abnormal physical
      conditions in the sense of acute adaptation to deep breath-hold diving. Dynamic
      magnetic resonance imaging is adequate for visualisation of the sequence of the
      glossopharyngeal insufflation manoeuvre and the complete reversibility of
      deliberate hyperinflation.

PMID- 18827158
TI  - Exacerbations and intent-to-treat analyses in randomised trials.

PMID- 18827159
TI  - Passive smoking and asthma death.

PMID- 18827160
TI  - Asymptomatic airway hyperresponsiveness: what does it mean?

PMID- 18827161
TI  - The effect of inhaled lidocaine-hydrofluoroalkane 134a in prednisone-dependent
      eosinophilic bronchitis.

PMID- 18827162
TI  - Dental units as infection sources of Pseudomonas aeruginosa.

PMID- 18827163
TI  - Impact of poor dental health on pneumonia.

PMID- 18827164
TI  - Reproducibility of exhaled breath condensate markers.

PMID- 18827165
TI  - Exhaled breath condensate is not suitable to detect EGFR somatic mutations.

PMID- 18827166
TI  - The potential for patient-led COPD admission avoidance schemes.

PMID- 18827167
TI  - Relationship between depression and exacerbations in COPD: a response.

PMID- 18827168
TI  - Inhibition of the renin-angiotensin system in severe COPD.

PMID- 18827169
TI  - Massive haemoptysis: the definition should be revised.

PMID- 18827170
TI  - Mortality predictive capacity of the 6-min walk distance.

PMID- 18827171
TI  - Aging differentially affects human skeletal muscle microRNA expression at rest
      and after an anabolic stimulus of resistance exercise and essential amino acids.
AB  - Sarcopenia, skeletal muscle loss during aging, is associated with increased
      falls, fractures, morbidity, and loss of independence. MicroRNAs (miRNAs) are
      novel posttranscriptional regulators. The role of miRNAs in cell size regulation
      after an anabolic stimulus in human skeletal muscle is unknown. We hypothesized
      that aging would be associated with a differential expression of skeletal muscle
      primary miRNA (pri-miRNA) and mature miRNA (miR). To test this hypothesis, we
      used real-time PCR and immunoblotting before and after an anabolic stimulus
      (resistance exercise + ingestion of a 20-g leucine-enriched essential amino acid
      solution) to measure the expression of muscle-specific miRNAs (miR-1, miR-133a,
      and miR-206), upstream regulators (MyoD and myogenin), and downstream targets
      [insulin-like growth factor-I, histone deacetylase-4, myocyte enhancing factor-2,
      and Ras homolog enriched in brain (Rheb)] in skeletal muscle of young and older
      men. Muscle biopsies were obtained at baseline and 3 and 6 h after exercise. At
      baseline, we found pri-miRNA-1-1, -1-2, -133a-1, and -133a-2 expression elevated
      in older compared with young men (P < 0.05). Pri-miRNA-1-2, -133a-1, and -133a-2
      were reduced at 6 h after exercise only in the young men compared with baseline,
      whereas pri-miRNA-206 was elevated at different postexercise time points in older
      and young men (P < 0.05). Compared with baseline, miR-1 was reduced only in the
      young men, whereas Rheb protein was increased in both age groups after the
      anabolic stimulus (P < 0.05). We conclude that skeletal muscle primary and mature
      miRNA expression in young men is readily altered by an anabolic stimulus of
      resistance exercise + essential amino acid ingestion. However, aging is
      associated with higher basal skeletal muscle primary miRNA expression and a
      dysregulated miRNA response after the anabolic stimulus.

PMID- 18827172
TI  - Divergent cell signaling after short-term intensified endurance training in human
      skeletal muscle.
AB  - Endurance training represents one extreme in the continuum of skeletal muscle
      plasticity. The molecular signals elicited in response to acute and chronic
      exercise and the integration of multiple intracellular pathways are incompletely
      understood. We determined the effect of 10 days of intensified cycle training on
      signal transduction in nine inactive males in response to a 1-h acute bout of
      cycling at the same absolute workload (164 +/- 9 W). Muscle biopsies were taken
      at rest and immediately and 3 h after the acute exercise. The metabolic signaling
      pathways, including AMP-activated protein kinase (AMPK) and mammalian target of
      rapamycin (mTOR), demonstrated divergent regulation by exercise after training.
      AMPK phosphorylation increased in response to exercise ( approximately 16-fold; P
      < 0.05), which was abrogated posttraining (P < 0.01). In contrast, mTOR
      phosphorylation increased in response to exercise ( approximately 2-fold; P <
      0.01), which was augmented posttraining (P < 0.01) in the presence of increased
      mTOR expression (P < 0.05). Exercise elicited divergent effects on mitogen
      activated protein kinase (MAPK) pathways after training, with exercise-induced
      extracellular signal-regulated kinase (ERK) 1/2 phosphorylation being abolished
      (P < 0.01) and p38 MAPK maintained. Finally, calmodulin kinase II (CaMKII)
      exercise-induced phosphorylation and activity were maintained (P < 0.01), despite
      increased expression ( approximately 2-fold; P < 0.05). In conclusion, 10 days of
      intensified endurance training attenuated AMPK, ERK1/2, and mTOR, but not CaMKII
      and p38 MAPK signaling, highlighting molecular pathways important for rapid
      functional adaptations and maintenance in response to intensified endurance
      exercise and training.

PMID- 18827173
TI  - Comment: tigecycline for the treatment of Acinetobacter infections: a case
      series.

PMID- 18827174
TI  - Comparison of the impact of the Atrial Fibrillation Follow-Up Investigation of
      Rhythm Management trial on prescribing patterns: a time-series analysis.
AB  - BACKGROUND: The AFFIRM (Atrial Fibrillation Follow-Up Investigation of Rhythm
      Management) trial demonstrated that rate control and rhythm control strategies
      result in similar survival and quality of life for patients with atrial
      fibrillation (AF). Because of superior safety and lower cost, rate control is now
      the recommended strategy for the management of most elderly, high-risk AF
      patients. OBJECTIVE: To determine the extent to which the AFFIRM trial results
      have been adopted into actual practice. METHODS: We conducted a time-series
      analysis of 3 population-based cohorts of patients with AF who were 66 years of
      age or older in Pennsylvania and Ontario. We stratified patients in Ontario by
      socioeconomic status (SES) and examined changes in quarterly prescription rates
      for rate control and rhythm controlling medications as well as cardioversion
      procedures before and after publication of the AFFIRM trial. RESULTS: The
      publication of the AFFIRM trial resulted in statistically significant reductions
      in the use of rhythm controlling medications in all 3 cohorts (p < 0.01). The
      magnitude of these changes in the non-low SES Canadian cohort was approximately
      1% per quarter and was greater than the magnitude observed in the other cohorts
      (p < 0.001). The use of cardioversion procedures also decreased in all study
      regions (p < 0.01). In contrast, AFFIRM publication was also associated with a
      small increase in the use of rate controlling medications in Canada (p < 0.01)
      but not in the US (p = 0.23). CONCLUSIONS: Publication of the AFFIRM trial
      resulted in small but statistically significant changes in the care of patients
      with AF.

PMID- 18827176
TI  - Blood pressure control with amlodipine add-on therapy in patients with
      hypertension and diabetes: results of the Amlodipine Diabetic Hypertension
      Efficacy Response Evaluation Trial.
AB  - BACKGROUND: Attainment of blood pressure (BP) goals in patients with diabetes is
      critical both to reduce the risk of cardiovascular events and to delay the
      progression of renal disease. While therapeutic guidelines advise initial therapy
      with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker,
      monotherapy with these agents may not be sufficient to attain target BP.
      OBJECTIVE: The ADHT (Amlodipine Diabetic Hypertension Efficacy Response
      Evaluation Trial) evaluated the efficacy and safety of adding amlodipine to the
      treatment regimen of patients with hypertension and diabetes who were already
      receiving either quinapril or losartan as monotherapy. METHODS: ADHT was a double
      blind, double-dummy, 22-week trial conducted in the US. After a washout period of
      7-13 days, patients (aged 30-75 y) with hypertension and diabetes were randomized
      to receive quinapril 20 mg/day plus placebo or losartan 50 mg/day plus placebo
      for 4 weeks, titrated to 40 mg or 100 mg (if required), respectively, for an
      additional 4 weeks to achieve their BP goals (<130/80 mm Hg). At week 8, either
      amlodipine 5 mg/day or placebo was added for an additional 12 weeks, with
      titration to 10 mg at week 14 if the BP goal was not achieved. RESULTS: Efficacy
      of add-on therapy was evaluated in 411 patients (amlodipine 211, placebo 200). BP
      goal was reached by 27.5% of patients when amlodipine was added to quinapril or
      losartan monotherapy, compared with 12.5% when placebo was added (OR 2.73; 95% CI
      1.61 to 4.64; p < 0.001). When added to quinapril or losartan monotherapy,
      amlodipine reduced BP by 8.1/5.4 mm Hg, compared with a 1.6/0.7 mm Hg decrease
      with add-on placebo (p < 0.001). Amlodipine, quinapril, and losartan were well
      tolerated. CONCLUSIONS: Amlodipine is safe and effective when added to quinapril
      or losartan monotherapy to help lower BP toward therapeutic targets in patients
      with hypertension and diabetes.

PMID- 18827177
TI  - Bevacizumab reduces the growth rate constants of renal carcinomas: a novel
      algorithm suggests early discontinuation of bevacizumab resulted in a lack of
      survival advantage.
AB  - BACKGROUND: To hasten cancer drug development, new paradigms are needed to assess
      therapeutic efficacy. In a randomized phase II study in patients with renal cell
      carcinoma, 10 microg/kg bevacizumab (Avastin; Genentech, Inc., South San
      Francisco, CA) administered every 2 weeks resulted in a longer time to
      progression but a statistically significant difference in overall survival could
      not be demonstrated. METHODS: We developed a novel two-phase equation to estimate
      concomitant rates of tumor regression (regression rate constant) and tumor growth
      (growth rate constant). This method allows us to assess therapeutic efficacy
      using tumor measurements gathered while a patient receives therapy in a clinical
      trial. RESULTS: The growth rate constants of renal cell carcinomas were
      significantly lower during therapy with 10 microg/kg bevacizumab than those of
      tumors in patients receiving placebo. In all cohorts the tumor growth rate
      constants were correlated with survival. That a survival advantage was not
      demonstrated with bevacizumab appears to have been a result of early
      discontinuation of bevacizumab. CONCLUSIONS: Single-agent bevacizumab
      significantly affects the growth rate constants of renal cell carcinoma.
      Extrapolating from the growth rate constants, we conclude that the failure to
      demonstrate a survival advantage in the original study was a result of premature
      discontinuation of bevacizumab. The mathematical model described herein has
      applications to many tumor types and should aid in evaluating the relative
      efficacies of different therapies. Quantitating tumor growth rate constants using
      data gathered while patients are enrolled in a clinical trial, as in the present
      study, may streamline and assist in drug development.

PMID- 18827180
TI  - Distribution and evolution of circular miniproteins in flowering plants.
AB  - Cyclotides are disulfide-rich miniproteins with the unique structural features of
      a circular backbone and knotted arrangement of three conserved disulfide bonds.
      Cyclotides have been found only in two plant families: in every analyzed species
      of the violet family (Violaceae) and in few species of the coffee family
      (Rubiaceae). In this study, we analyzed >200 Rubiaceae species and confirmed the
      presence of cyclotides in 22 species. Additionally, we analyzed >140 species in
      related plant families to Rubiaceae and Violaceae and report the occurrence of
      cyclotides in the Apocynaceae. We further report new cyclotide sequences that
      provide insights into the mechanistic basis of cyclotide evolution. On the basis
      of the phylogeny of cyclotide-bearing plants and the analysis of cyclotide
      precursor gene sequences, we hypothesize that cyclotide evolution occurred
      independently in various plant families after the divergence of Asterids and
      Rosids ( approximately 125 million years ago). This is strongly supported by
      recent findings on the in planta biosynthesis of cyclotides, which involves the
      serendipitous recruitment of ubiquitous proteolytic enzymes for cyclization. We
      further predict that the number of cyclotides within the Rubiaceae may exceed
      tens of thousands, potentially making cyclotides one of the largest protein
      families in the plant kingdom.

PMID- 18827181
TI  - Release of the repressive activity of rice DELLA protein SLR1 by gibberellin does
      not require SLR1 degradation in the gid2 mutant.
AB  - The rice (Oryza sativa) DELLA protein SLR1 acts as a repressor of gibberellin
      (GA) signaling. GA perception by GID1 causes SLR1 protein degradation involving
      the F-box protein GID2; this triggers GA-associated responses such as shoot
      elongation and seed germination. In GA-insensitive and GA biosynthesis mutants,
      SLENDER RICE1 (SLR1) accumulates to high levels, and the severity of dwarfism is
      usually correlated with the level of SLR1 accumulation. An exception is the GA
      insensitive F-box mutant gid2, which shows milder dwarfism than mutants such as
      gid1 and cps even though it accumulates higher levels of SLR1. The level of SLR1
      protein in gid2 was decreased by loss of GID1 function or treatment with a GA
      biosynthesis inhibitor, and dwarfism was enhanced. Conversely, overproduction of
      GID1 or treatment with GA(3) increased the SLR1 level in gid2 and reduced
      dwarfism. These results indicate that derepression of SLR1 repressive activity
      can be accomplished by GA and GID1 alone and does not require F-box (GID2)
      function. Evidence for GA signaling without GID2 was also provided by the
      expression behavior of GA-regulated genes such as GA-20oxidase1, GID1, and SLR1
      in the gid2 mutant. Based on these observations, we propose a model for the
      release of GA suppression that does not require DELLA protein degradation.

PMID- 18827182
TI  - Proteolysis-independent downregulation of DELLA repression in Arabidopsis by the
      gibberellin receptor GIBBERELLIN INSENSITIVE DWARF1.
AB  - This article presents evidence that DELLA repression of gibberellin (GA)
      signaling is relieved both by proteolysis-dependent and -independent pathways in
      Arabidopsis thaliana. DELLA proteins are negative regulators of GA responses,
      including seed germination, stem elongation, and fertility. GA stimulates GA
      responses by causing DELLA repressor degradation via the ubiquitin-proteasome
      pathway. DELLA degradation requires GA biosynthesis, three functionally redundant
      GA receptors GIBBERELLIN INSENSITIVE DWARF1 (GID1a, b, and c), and the SLEEPY1
      (SLY1) F-box subunit of an SCF E3 ubiquitin ligase. The sly1 mutants accumulate
      more DELLA proteins but display less severe dwarf and germination phenotypes than
      the GA biosynthesis mutant ga1-3 or the gid1abc triple mutant. Interestingly,
      GID1 overexpression rescued the sly1 dwarf and infertility phenotypes without
      decreasing the accumulation of the DELLA protein REPRESSOR OF ga1-3. GID1 rescue
      of sly1 mutants was dependent on the level of GID1 protein, GA, and the presence
      of a functional DELLA motif. Since DELLA shows increasing interaction with GID1
      with increasing GA levels, it appears that GA-bound GID1 can block DELLA
      repressor activity by direct protein-protein interaction with the DELLA domain.
      Thus, a SLY1-independent mechanism for GA signaling may function without DELLA
      degradation.

PMID- 18827183
TI  - Time from diagnosis to treatment initiation predicts survival in younger, but not
      older, acute myeloid leukemia patients.
AB  - Acute myeloid leukemia (AML) is considered an oncologic emergency. Delaying
      induction chemotherapy until molecular testing results return, may benefit some
      patients but harm others. We examined the effect of time from AML diagnosis to
      treatment (TDT) on complete remission (CR) and overall survival (OS), using
      patient characteristics available at diagnosis. Regression models were applied to
      older (> or = 60 years) and younger (< 60 years) adults, controlling for age,
      baseline white blood cell count, secondary AML (sAML), and performance status.
      Median patient age was 60 years (range, 17-87 years), TDT 4 days (range, 1-78
      days), and 45% had sAML. Cytogenetic risk distribution was: favorable, 8%;
      intermediate, 66%; unfavorable, 26%. CR rate was 67% and median OS was 68 weeks
      in patients younger than 60 years; 55% and 33 weeks in older patients,
      respectively. In univariate and multivariate analyses, longer TDT was associated
      with worse CR and OS in younger (univariate: P < .001 in both; multivariate: P <
      .001 and P = .001, respectively), but not older patients (univariate: P = .45, P
      = .19; multivariate: P = .63, P = .30, respectively). Results did not change with
      inclusion of cytogenetic data or in risk group subsets. AML therapy should be
      initiated immediately in younger patients. Delaying treatment does not seem
      harmful in older patients, allowing individualized approaches.

PMID- 18827184
TI  - CD4+CD25+ T cells alloactivated ex vivo by IL-2 or IL-4 become potent alloantigen
      specific inhibitors of rejection with different phenotypes, suggesting separate
      pathways of activation by Th1 and Th2 responses.
AB  - CD4(+)CD25(+)Foxp3(+) T cells are regulatory/suppressor cells (Tregs) that
      include non-antigen (Ag)-specific as well as Ag-specific Tregs. How non-Ag
      specific naive CD4(+)CD25(+) Treg develop into specific Tregs is unknown. Here,
      we generated adaptive Tregs by culture of naive CD4(+)CD25(+)Foxp3(+) T cells
      with allo-Ag and either interleukin-2 (IL-2) or IL-4. Within days, IL-2 enhanced
      interferon-gamma receptor (Ifngammar) and Il-5 mRNA and IL-4 induced a reciprocal
      profile with de novo IL-5Ralpha and increased IFN-gamma mRNA expression. Both IL
      2- and IL-4-alloactivated CD4(+)CD25(+) Tregs within 3 to 4 days of culture had
      enhanced capacity to induce tolerance to specific donor but not to third-party
      cardiac allografts. These hosts became tolerant as allografts functioned more
      than 250 days, with a physiologic ratio of less than 10% CD4(+)CD25(+)Foxp3(+) T
      cells in the CD4(+) population. CD4(+)CD25(+) T cells from tolerant hosts given
      IL-2-cultured cells had increased Il-5 and Ifngammar mRNA. Those from hosts given
      IL-4-cultured cells had enhanced IL-5Ralpha mRNA expression and IL-5 enhanced
      their proliferation to donor but not third-party allo-Ag. Thus, IL-2 and IL-4
      activated allo-Ag-specific Tregs with distinct phenotypes that were retained in
      vivo. These findings suggested that T-helper 1 (Th1) and Th2 responses activate 2
      pathways of adaptive Ag-specific Tregs that mediate tolerance. We propose they be
      known as T-suppressor 1 (Ts1) and Ts2 cells.

PMID- 18827186
TI  - cIAP1-dependent TRAF2 degradation regulates the differentiation of monocytes into
      macrophages and their response to CD40 ligand.
AB  - Peripheral blood monocytes are plastic cells that migrate to tissues and
      differentiate into various cell types, including macrophages, dendritic cells,
      and osteoclasts. We have described the migration of cellular inhibitor of
      apoptosis protein 1 (cIAP1), a member of the IAP family of proteins, from the
      nucleus to the Golgi apparatus in monocytes undergoing differentiation into
      macrophages. Here we show that, once in the cytoplasm, cIAP1 is involved in the
      degradation of the adaptor protein tumor necrosis factor receptor-associated
      factor 2 (TRAF2) by the proteosomal machinery. Inhibition of cIAP1 prevents the
      decrease in TRAF2 expression that characterizes macrophage formation. We
      demonstrate that TRAF2 is initially required for macrophage differentiation as
      its silencing prevents Ikappa-Balpha degradation, nuclear factor-kappaB (NF
      kappaB) p65 nuclear translocation, and the differentiation process. Then, we show
      that cIAP1-mediated degradation of TRAF2 allows the differentiation process to
      progress. This degradation is required for the macrophages to be fully functional
      as TRAF2 overexpression in differentiated cells decreases the c-Jun N-terminal
      kinase-mediated synthesis and the secretion of proinflammatory cytokines, such as
      interleukin-8 and monocyte chemoattractant protein 1 (MCP-1) in response to CD40
      ligand. We conclude that TRAF2 expression and subsequent degradation are required
      for the differentiation of monocytes into fully functional macrophages.

PMID- 18827185
TI  - Molecular biology of bcr-abl1-positive chronic myeloid leukemia.
AB  - Chronic myeloid leukemia (CML) has been regarded as the paradigmatic example of a
      malignancy defined by a unique molecular event, the BCR-ABL1 oncogene. Decades of
      research zeroing in on the role of BCR-ABL1 kinase in the pathogenesis of CML
      have culminated in the development of highly efficacious therapeutics that, like
      imatinib mesylate, target the oncogenic kinase activity of BCR-ABL1. In recent
      years, most research efforts in CML have been devoted to developing novel
      tyrosine kinase inhibitors (TKIs) as well as to elucidating the mechanisms of
      resistance to imatinib and other TKIs. Nonetheless, primordial aspects of the
      pathogenesis of CML, such as the mechanisms responsible for the transition from
      chronic phase to blast crisis, the causes of genomic instability and faulty DNA
      repair, the phenomenon of stem cell quiescence, the role of tumor suppressors in
      TKI resistance and CML progression, or the cross-talk between BCR-ABL1 and other
      oncogenic signaling pathways, still remain poorly understood. Herein, we
      synthesize the most relevant and current knowledge on such areas of the
      pathogenesis of CML.

PMID- 18827187
TI  - Correlation of proinflammatory and anti-inflammatory cytokine levels with
      histopathological changes in an adult mouse lung model of Campylobacter jejuni
      infection.
AB  - Campylobacter jejuni is a major cause of diarrhea in humans. A mouse lung model
      of infection was previously established for C. jejuni. We used this model to
      study cytokine production in the lungs and correlated it with pathological
      changes. C. jejuni strain 81-176 or sterile phosphate-buffered saline was
      intranasally inoculated into adult BALB/c mice. The levels of proinflammatory
      cytokines (gamma interferon, tumor necrosis factor alpha, interleukin-1beta [IL
      1beta], IL-2) and anti-inflammatory cytokines (IL-4, IL-10), in addition to those
      of IL-6, were assessed on days 1, 3, and 5 postinfection by enzyme-linked
      immunosorbent assay, and the ratios of proinflammatory cytokines to anti
      inflammatory cytokines were calculated. Since IL-6 is unique in that it is both a
      proinflammatory cytokine and a TH2 cytokine, it was considered to be both in the
      determination of these ratios. The significance of the cytokine levels and ratios
      were determined by the Mann-Whitney U test (P<or=0.05). The induction of
      proinflammatory cytokines in the lungs of infected mice, as indicated by the
      cytokine levels and ratios, coincided with the accumulation of neutrophils and
      activated macrophages, in addition to the clearance of the bacterial load and
      bacteriumlike structures that we have previously shown in the same groups of
      mice. This was followed by increased levels of anti-inflammatory cytokines and
      the resolution of inflammation and pathology in the lungs. This study
      demonstrates the dynamics of cytokine production and their correlation with
      tissue inflammation and the resolution of infection. This model is useful for
      further studies of the pathogenesis of C. jejuni infection and vaccine
      evaluation.

PMID- 18827188
TI  - Validation of an enzyme-linked immunosorbent assay for diagnosis of human
      trichinellosis.
AB  - Trichinellosis is a zoonotic disease caused by the consumption of raw or semiraw
      meat from different animals harboring Trichinella larvae in their muscles. Since
      there are no pathognomonic signs, diagnosis can be difficult; for this reason,
      serology is important. The objective of this study was to validate an enzyme
      linked immunosorbent assay (ELISA) using excretory/secretory antigens to detect
      anti-Trichinella immunoglobulin G antibodies in human sera. A total of 3,505
      human serum samples were tested. A receiver-operator characteristic (ROC) curve
      analysis was performed. The accuracy of the test was determined by calculating
      the area under the curve, which was equal to 0.999, indicating high accuracy. The
      coefficient of variation calculated for data from four serum samples in eight
      working sessions was no higher than 5% for the positive sera or 14% for the
      negative sera. Moreover, the analysis of the differences in optical density
      between duplicates indicated a high repeatability for the ELISA. At the ROC
      optimized cutoff, the sensitivity and specificity of the test were, respectively,
      99.2% and 90.6% (specificity of 95.6% when excluding the samples from
      multiparasitized persons from Tanzania). The validated ELISA showed good
      performance in terms of sensitivity, repeatability, and reproducibility, whereas
      the specificity was limited. These results suggest that this test is suitable for
      detecting anti-Trichinella antibodies in human sera for diagnostic purposes,
      whereas its use in epidemiological surveys could be questionable.

PMID- 18827189
TI  - Expression of antimicrobial peptides in cecal tonsils of chickens treated with
      probiotics and infected with Salmonella enterica serovar typhimurium.
AB  - Several strategies currently exist for control of Salmonella enterica serovar
      Typhimurium colonization in the chicken intestine, among which the use of
      probiotics is of note. Little is known about the underlying mechanisms of
      probiotic-mediated reduction of Salmonella colonization. In this study, we asked
      whether the effect of probiotics is mediated by antimicrobial peptides, including
      avian beta-defensins (also called gallinacins) and cathelicidins. Four treatment
      groups were included in this study: a negative-control group, a probiotic-treated
      group, a Salmonella-infected group, and a probiotic-treated and Salmonella
      infected group. On days 1, 3, and 5 postinfection (p.i.), the cecal tonsils were
      removed, and RNA was extracted and used for measurement of avian beta-defensin 1
      (AvBD1), AvBD2, AvBD4, AvBD6, and cathelicidin gene expression by real-time PCR.
      The expressions of all avian beta-defensins and cathelicidin were detectable in
      all groups, irrespective of treatment and time point. Probiotic treatment and
      Salmonella infection did not affect the expression of any of the investigated
      genes on day 1 p.i. Furthermore, probiotic treatment had no significant effect on
      the expression of the genes at either 3 or 5 days p.i. However, the expression
      levels of all five genes were significantly increased (P < 0.05) in response to
      Salmonella infection at 3 and 5 days p.i. However, administration of probiotics
      eliminated the effect of Salmonella infection on the expression of antimicrobial
      genes. These findings indicate that the expression of antimicrobial peptides may
      be repressed by probiotics in combination with Salmonella infection or,
      alternatively, point to the possibility that, due to a reduction in Salmonella
      load in the intestine, these genes may not be induced.

PMID- 18827190
TI  - Assessment of three commercially available serologic assays for detection of
      antibodies to Mycobacterium tuberculosis and identification of active
      tuberculosis.
AB  - Tuberculosis (TB) caused by Mycobacterium tuberculosis remains a major world
      disease, with approximately 9 million new cases each year. Identification and
      treatment of active disease are essential for TB control. Serology may offer
      increased detection of active disease in patients with a positive tuberculin skin
      test (TST) or QuantiFERON-TB (QFT-G). The InBios Active TbDetect immunoglobulin G
      (IgG) enzyme-linked immunosorbent assay (ELISA), IBL M. tuberculosis IgG ELISA,
      and Anda Biologics TB ELISAs were evaluated for the ability to detect M.
      tuberculosis antibodies in patients with active disease. Agreement, sensitivity,
      and specificity for each ELISA were determined and compared to those for culture
      or amplified direct detection and M. tuberculosis low-risk control patients. The
      InBios Active TbDetect ELISA had an agreement of 96.2%, a sensitivity of 83.3%,
      and a specificity of 98.9%. The IBL M. tuberculosis ELISA had an agreement of
      84.0%, a sensitivity of 5.6%, and a specificity of 100.0%. The agreement,
      sensitivity, and specificity of the Anda Biologics TB ELISA were 74.2%, 83.3%,
      and 72.0%, respectively. The sensitivity for detecting M. tuberculosis antibodies
      in human immunodeficiency virus-associated TB was 50% for both the InBios Active
      TbDetect ELISA and the Anda Biologics TB ELISA and 0% for the IBL M. tuberculosis
      ELISA. The positivity rates for InBios Active TbDetect ELISA, IBL M. tuberculosis
      ELISA, and Anda Biologics TB ELISA in latently infected individuals positive by
      TST and/or QFT-G were 5.1%, 0.0%, and 30.8%, respectively. It can be concluded
      that the InBios Active TbDetect IgG ELISA is superior to the other ELISAs in
      accurately detecting active TB.

PMID- 18827191
TI  - Seroprevalence of antibodies against serogroup C meningococci in England in the
      postvaccination era.
AB  - The United Kingdom introduced meningococcal serogroup C conjugate (MCC) vaccines
      in 1999, resulting in substantial declines in serogroup C disease and carriage.
      Here, we measured the age-specific prevalence of serum bactericidal antibodies
      (SBA) to Neisseria meningitidis serogroup C and immunoglobulin G (IgG)
      concentrations to serogroups A, C, W-135, and Y in 2,673 serum samples collected
      in England between 2000 and 2004. We compared the seroprevalence of SBA titers of
      > or =8 in the postvaccination era with results from an earlier prevaccination
      study conducted using the same methods. We found that the percentages of
      individuals with protective SBA titers were higher in 2000 to 2004 in all of the
      age groups targeted for MCC vaccination. In the postvaccine era, the prevalence
      of protective titers was high (75%) in children who had recently been offered
      routine immunization, but this fell to 36% more than 18 months after scheduled
      immunization. In the cohorts targeted in the catch-up campaign, the percentage
      achieving SBA titers of > or =8 was higher in children offered the vaccine at
      ages 5 to 17 years than in children offered the vaccine at ages 1 to 4 years. The
      geometric mean concentration (GMC) IgG for serogroup C followed a similar
      pattern, corresponding to the age at and time since scheduled MCC vaccination.
      Serogroup-specific IgG GMCs for W-135 and Y were low and showed little variation
      by age. Serogroup A IgG GMCs were higher, possibly reflecting exposure to cross
      reacting antigens. Although the incidence of serogroup C disease remains low due
      to persisting herd effects, population antibody levels to serogroup C
      meningococci should be monitored so that potentially susceptible age groups can
      be identified should herd immunity wane.

PMID- 18827192
TI  - Evaluation of a commercial immunoblot, Helicoblot 2.1, for diagnosis of
      Helicobacter pylori infection.
AB  - The best method to diagnose Helicobacter pylori infection in different clinical
      situations is controversial. The aim of the study was to assess the performance
      of a commercial immunoblot, Helicoblot 2.1. The study comprised 215 patients, who
      were grouped according to the presence of H. pylori infection (assessed by two
      gastroscopies including histology with a median interval of 7.1 years, enzyme
      immunoassay [EIA]-based serology, and history of previous H. pylori infections
      and eradication therapies) into four categories: no H. pylori infection ever,
      previous infection, ongoing infection, and EIA seropositivity as the only marker
      of a possible previous infection. The sensitivity of Helicoblot 2.1 to show an
      ongoing or previous H. pylori infection was 100% and 92%, respectively.
      Helicoblot 2.1 was negative in only 80% of individuals with no evidence of
      present or previous infection but in 96% of patients 50 years of age or younger.
      The current infection marker of the immunoblot was positive in 49% of patients
      with successful H. pylori eradication therapy. After successful eradication
      therapy, Helicoblot 2.1 sustained positive results in 87% of patients, and CagA
      positivity was detected in 87% of patients with follow-up samples for more than
      10 years after therapy. Helicoblot 2.1 is a sensitive and, among patients of ages
      50 years or younger, a specific test in the primary diagnosis of H. pylori
      infection. However, it does not discriminate between past and current infections.
      It can be used in epidemiological studies assessing the role of H. pylori in
      different late sequelae.

PMID- 18827193
TI  - Recombinant multiepitope protein for diagnosis of leptospirosis.
AB  - Leptospirosis is an emerging infectious disease and is considered to be the most
      widespread zoonotic disease in the world. It can be misdiagnosed because
      manifestations of this febrile disease vary from mild flu-like symptoms to severe
      illness involving vital organs such as the liver and lungs. Therefore, accurate
      diagnosis for differentiation of leptospirosis from other pyrogenic infections
      prevailing in the same locality is imperative for proper treatment. Here, we
      report a customized recombinant leptospirosis multiepitope protein (r-LMP) that
      can specifically detect the immunoglobulin class of anti-leptospirosis antibodies
      in patient sera. Immunodominant epitopes from leptospire outer membrane proteins
      OmpL1, LipL21, and LipL32 were predicted and confirmed using phage display and
      immunity reaction. On the basis of the sequences of the identified epitopes, five
      major immunodominant epitopes were selected to construct a synthetic gene,
      recombinant lmp. The recombinant lmp gene was doubled and expressed in
      Escherichia coli. The recombinant protein was purified and used as an antigen to
      develop an enzyme-linked immunosorbent assay for detection of special
      immunoglobulin M (IgM) or IgG in sera from patients with leptospirosis or other
      febrile illnesses and healthy subjects. The results showed that the r-LMP protein
      recognized IgG and IgM in all the sera that were microscope agglutination test
      positive, and there were no cross-reactions with other patient sera. This
      approach of creating customized antigens coupled to overexpression and simple
      purification offers a promising alternative option for leptospirosis diagnosis,
      with the potential to circumvent the drawbacks of whole-leptospirosis-antigen
      based assays.

PMID- 18827194
TI  - Enhanced gamma interferon responses of mouse spleen cells following immunotherapy
      for tuberculosis relapse.
AB  - Gamma interferon responses of spleen cells in mice were examined during
      postchemotherapy relapse of intraperitoneally induced latent tuberculous
      infection. The mycobacterial extract RUTI, which prevented the relapse,
      significantly enhanced the immune responses to secreted and structural
      recombinant mycobacterial antigens, suggesting that RUTI-mediated protection was
      mediated by activated T cells.

PMID- 18827195
TI  - Orally administered Mycobacterium vaccae modulates expression of immunoregulatory
      molecules in BALB/c mice with pulmonary tuberculosis.
AB  - The environmental saprophyte Mycobacterium vaccae induces a Th1 response and
      cytotoxic T cells that recognize M. tuberculosis, and by subcutaneous injection,
      it is therapeutic for pulmonary tuberculosis (TB) induced by high-dose challenge
      in BALB/c mice. However, M. vaccae also drives regulatory T cells that inhibit
      Th2 responses, and this is seen in allergy models, not only following
      subcutaneous injection but also after oral administration. An oral
      immunotherapeutic for TB would be clinically useful, so we investigated M. vaccae
      given orally by gavage at 28-day intervals in the TB model. We used two different
      protocols: starting the oral M. vaccae either 1 day before or 32 days after
      infection with M. tuberculosis. Throughout the infection (until 120 days), we
      monitored outcome (CFU), molecules involved in the development of
      immunoregulation (Foxp3, hemoxygenase 1, idoleamine 2,3-dioxygenase, and
      transforming growth factor beta [TGF-beta]), and indicators of cytokine balance
      (tumor necrosis factor, inducible nitric oxide synthase, interleukin-4 [IL-4],
      and IL-4delta2; an inhibitory splice variant of IL-4 associated with improved
      outcome in human TB). Oral M. vaccae had a significant effect on CFU and led to
      increased expression of Th1 markers and of IL-4delta2, while suppressing IL-4,
      Foxp3, and TGF-beta. When administered 1 day before infection, oral M. vaccae
      induced a striking peak of expression of hemoxygenase 1. In conclusion, we show
      novel information about the expression in TB of murine IL-4delta2 and molecules
      involved in immunoregulation and show that these can be modulated by oral
      administration of a saprophytic mycobacterium. A clinical trial of oral M. vaccae
      in extensively drug-resistant TB might be justified.

PMID- 18827196
TI  - An 82-year-old woman with worsening hypertension: review of renal artery
      stenosis.
AB  - Renal artery stenosis (RAS) is a common disorder in adults with atherosclerosis
      and is associated with hypertension, impaired renal function, congestive heart
      failure, and angina pectoris. The incidence of RAS is increasing because of the
      aging of the US population and increasing prevalence of atherosclerosis. The case
      of Mrs S, an 82-year-old woman with long-standing hypertension and unilateral RAS
      detected by magnetic resonance angiography, illustrates the challenges
      surrounding indications for revascularization. The discussion reviews the
      clinical presentation and natural history of RAS and strategies for diagnosis.
      The role of medical therapy, surgery, and endovascular therapy are reviewed,
      particularly in the context of guidelines and systematic reviews to help
      clinicians and patients facing this challenging decision.

PMID- 18827197
TI  - The cover. West Church, Boston.

PMID- 18827198
TI  - A piece of my mind. The physician in winter.

PMID- 18827199
TI  - Risks and benefits of direct-to-consumer genetic testing remain unclear.

PMID- 18827200
TI  - Emergency departments see high rates of adverse events from antibiotic use.

PMID- 18827201
TI  - Cerumen removal guidelines wax practical.

PMID- 18827202
TI  - Researchers devise innovative method to overcome cancer-related drug resistance.

PMID- 18827203
TI  - Ultrasound and mammography for breast cancer screening.

PMID- 18827204
TI  - Ultrasound and mammography for breast cancer screening.

PMID- 18827205
TI  - Nonmammographic screening for breast cancer.

PMID- 18827206
TI  - Request for complementary medicine after brain death.

PMID- 18827207
TI  - Request for complementary medicine after brain death.

PMID- 18827208
TI  - Driving fatalities on US presidential election days.

PMID- 18827209
TI  - Variants of the adiponectin (ADIPOQ) and adiponectin receptor 1 (ADIPOR1) genes
      and colorectal cancer risk.
AB  - CONTEXT: Current epidemiological evidence suggests an association between
      obesity, hyperinsulinemia, and colorectal cancer risk. Adiponectin is a hormone
      secreted by the adipose tissue, and serum levels are inversely correlated with
      obesity and hyperinsulinemia. While there is evidence of an association between
      circulating adiponectin levels and colorectal cancer risk, no association between
      genes of the adiponectin pathway and colorectal cancer have been reported to
      date. OBJECTIVE: To determine the association of 10 haplotype-tagging single
      nucleotide polymorphisms (SNPs) of the adiponectin (ADIPOQ) and adiponectin
      receptor 1 (ADIPOR1) genes with colorectal cancer risk. DESIGN, SETTING, AND
      PATIENTS: Two case-control studies including patients with a diagnosis of
      colorectal cancer and controls were recruited between 2000 and 2007. Case-control
      study 1 included a total of 441 patients with a diagnosis of colorectal cancer
      and 658 controls; both groups were of Ashkenazi Jewish ancestry and from New
      York, New York. Case-control study 2 included 199 patients with a diagnosis of
      colorectal cancer and 199 controls from Chicago, Illinois, matched 1:1 for sex,
      age, and ethnicity. MAIN OUTCOME MEASURES: ADIPOQ and ADIPOR1 SNP frequency among
      cases and controls. RESULTS: In study 1, after adjustment for age, sex, and SNPs
      from the same gene, 3 ADIPOQ SNPs and 1 ADIPOR1 SNP were associated with
      colorectal cancer risk: rs266729 (adjusted odds ratio [AOR], 0.72; 95% confidence
      interval [CI], 0.55-0.95) and rs822396 (AOR, 0.37; 95% CI, 0.14-1.00) were
      associated with decreased risk whereas rs822395 (AOR, 1.76; 95% CI, 1.09-2.84)
      and rs1342387 (AOR, 1.79; 95% CI, 1.18-2.72) were associated with increased risk.
      In study 2, after adjustment for age, sex, race, and SNPs from the same gene, the
      ADIPOQ SNP rs266729 was associated with a decreased colorectal cancer risk of
      similar magnitude as in study 1 (AOR, 0.52; 95% CI, 0.34-0.78). Combined analysis
      of both studies shows an association of rs266729 with decreased colorectal cancer
      risk (AOR, 0.73; 95% CI, 0.53-0.99). CONCLUSION: The SNP rs266729, which tags the
      5' flanking region of the ADIPOQ gene, is associated with decreased colorectal
      cancer risk.

PMID- 18827210
TI  - Effects of a reduced dose schedule and intramuscular administration of anthrax
      vaccine adsorbed on immunogenicity and safety at 7 months: a randomized trial.
AB  - CONTEXT: In 1999, the US Congress directed the Centers for Disease Control and
      Prevention to conduct a pivotal safety and efficacy study of anthrax vaccine
      adsorbed (AVA). OBJECTIVE: To determine the effects on serological responses and
      injection site adverse events (AEs) resulting from changing the route of
      administration of AVA from subcutaneous (s.q.) to intramuscular (i.m.) and
      omitting the week 2 dose from the licensed schedule. DESIGN, SETTING, AND
      PARTICIPANTS: Assessment of the first 1005 enrollees in a multisite, randomized,
      double-blind, noninferiority, phase 4 human clinical trial (ongoing from May
      2002). INTERVENTION: Healthy adults received AVA by the s.q. (reference group) or
      i.m. route at 0, 2, and 4 weeks and 6 months (4-SQ or 4-IM; n = 165-170 per
      group) or at a reduced 3-dose schedule (3-IM; n = 501). A control group (n = 169)
      received saline injections at the same time intervals. MAIN OUTCOME MEASURES:
      Noninferiority at week 8 and month 7 of anti-protective antigen IgG geometric
      mean concentration (GMC), geometric mean titer (GMT), and proportion of
      responders with a 4-fold rise in titer (%4 x R). Reactogenicity outcomes were
      proportions of injection site and systemic AEs. RESULTS: At week 8, the 4-IM
      group (GMC, 90.8 microg/mL; GMT, 1114.8; %4 x R, 97.7) was noninferior to the 4
      SQ group (GMC, 105.1 microg/mL; GMT, 1315.4; %4 x R, 98.8) for all 3 primary end
      points. The 3-IM group was noninferior for only the %4 x R (GMC, 52.2 microg/mL;
      GMT, 650.6; %4 x R, 94.4). At month 7, all groups were noninferior to the
      licensed regimen for all end points. Solicited injection site AEs assessed during
      examinations occurred at lower proportions in the 4-IM group compared with 4-SQ.
      The odds ratio for ordinal end point pain reported immediately after injection
      was reduced by 50% for the 4-IM vs 4-SQ groups (P < .001). Route of
      administration did not significantly influence the occurrence of systemic AEs.
      CONCLUSIONS: The 4-IM and 3-IM regimens of AVA provided noninferior immunological
      priming by month 7 when compared with the 4-SQ licensed regimen. Intramuscular
      administration significantly reduced the occurrence of injection site AEs. Trial
      Registration clinicaltrials.gov Identifier: NCT00119067.

PMID- 18827211
TI  - News media coverage of medication research: reporting pharmaceutical company
      funding and use of generic medication names.
AB  - CONTEXT: The news media are an important source of information about medical
      research for patients and even some physicians. Little is known about how
      frequently news articles report when medication research has received funding
      from pharmaceutical companies or how frequently news articles use generic vs
      brand medication names. OBJECTIVES: To assess the reporting of pharmaceutical
      company funding and generic medication name use in news articles about medication
      studies and to determine the views of newspaper editors about these issues.
      DESIGN, SETTING, AND PARTICIPANTS: We reviewed US news articles from newspaper
      and online sources about all pharmaceutical company-funded medication studies
      published in the 5 most prominent general medical journals between April 1, 2004,
      and April 30, 2008. We also surveyed editors at the 100 most widely circulated
      newspapers in the United States. MAIN OUTCOME MEASURES: The percentage of news
      articles indicating when studies have been pharmaceutical company-funded and the
      percentage that refer to medications by their generic vs brand names. Also the
      percentage of newspaper editors who indicate that their articles report
      pharmaceutical company funding; the percentage of editors who indicate that their
      articles refer to medications by generic names; and the percentage of newspapers
      with policies about these issues. RESULTS: Of the 306 news articles about
      medication research identified,130 (42%; 95% confidence interval [CI], 37%-48%)
      did not report that the research had received company funding. Of the 277 of
      these articles reporting on medications with both generic and brand names, 186
      (67%; 95% CI, 61%-73%) referred to the study medications by their brand names in
      at least half of the medication references. Eighty-two of the 93 (88%) newspaper
      editors who responded to our survey reported that articles from their
      publications always or often indicated when studies had received company funding
      (95% CI, 80%-94%), and 71 of 92 (77%) responding editors also reported that
      articles from their publications always or often referred to medications by the
      generic names (95% CI, 67%-85%). However, only 3 of 92 newspapers (3%) had
      written policies stating that company funding sources of medical studies be
      reported (95% CI 1%-9%), and 2 of 93 (2%) newspapers had written policies stating
      that medications should be referred to by their generic names (95% CI 1%-8%).
      CONCLUSION: News articles reporting on medication studies often fail to report
      pharmaceutical company funding and frequently refer to medications by their brand
      names despite newspaper editors' contention that this is not the case.

PMID- 18827212
TI  - Effectiveness of long-term psychodynamic psychotherapy: a meta-analysis.
AB  - CONTEXT: The place of long-term psychodynamic psychotherapy (LTPP) within
      psychiatry is controversial. Convincing outcome research for LTPP has been
      lacking. OBJECTIVE: To examine the effects of LTPP, especially in complex mental
      disorders, ie, patients with personality disorders, chronic mental disorders,
      multiple mental disorders, and complex depressive and anxiety disorders (ie,
      associated with chronic course and/or multiple mental disorders), by performing a
      meta-analysis. DATA SOURCES: Studies of LTPP published between January 1, 1960,
      and May 31, 2008, were identified by a computerized search using MEDLINE,
      PsycINFO, and Current Contents, supplemented by contact with experts in the
      field. STUDY SELECTION: Only studies that used individual psychodynamic
      psychotherapy lasting for at least a year, or 50 sessions; had a prospective
      design; and reported reliable outcome measures were included. Randomized
      controlled trials (RCTs) and observational studies were considered. Twenty-three
      studies involving a total of 1053 patients were included (11 RCTs and 12
      observational studies). DATA EXTRACTION: Information on study characteristics and
      treatment outcome was extracted by 2 independent raters. Effect sizes were
      calculated for overall effectiveness, target problems, general psychiatric
      symptoms, personality functioning, and social functioning. To examine the
      stability of outcome, effect sizes were calculated separately for end-of-therapy
      and follow-up assessment. RESULTS: According to comparative analyses of
      controlled trials, LTPP showed significantly higher outcomes in overall
      effectiveness, target problems, and personality functioning than shorter forms of
      psychotherapy. With regard to overall effectiveness, a between-group effect size
      of 1.8 (95% confidence interval [CI], 0.7-3.4) indicated that after treatment
      with LTPP patients with complex mental disorders on average were better off than
      96% of the patients in the comparison groups (P = .002). According to subgroup
      analyses, LTPP yielded significant, large, and stable within-group effect sizes
      across various and particularly complex mental disorders (range, 0.78-1.98).
      CONCLUSIONS: There is evidence that LTPP is an effective treatment for complex
      mental disorders. Further research should address the outcome of LTPP in specific
      mental disorders and should include cost-effectiveness analyses.

PMID- 18827213
TI  - The right to bear arms: constitutional law, politics, and public health.

PMID- 18827214
TI  - Nosocomial infection, the Deficit Reduction Act, and incentives for hospitals.

PMID- 18827215
TI  - The conflict between complex systems and reductionism.

PMID- 18827216
TI  - Closed-chest cardiac massage: progress measured by the exceptions.

PMID- 18827217
TI  - Update on JAMA's Policy on Release of Information to the Public.

PMID- 18827218
TI  - Psychodynamic psychotherapy and research evidence: Bambi survives Godzilla?

PMID- 18827219
TI  - JAMA patient page. Mild cognitive impairment.

PMID- 18827220
TI  - A Wnt-fall for gene regulation: repression.
AB  - A major endpoint of the canonical Wnt signaling pathway is a change in the
      transcription of target genes. The transcription factors lymphoid enhancer factor
      (LEF) and T cell factor (TCF) serve as the main gatekeepers of these changes by
      selecting genes to be targeted by the transcriptional coregulator beta-catenin
      and by defining how target gene expression will be altered. Most research has
      focused on LEF/TCF:beta-catenin-mediated activation of transcription, but there
      have been some reports that suggest that this complex also directly represses
      transcription. A recent study uncovered a new mode of repression of Wnt target
      genes in which recognition of a novel DNA element by TCF specifies that beta
      catenin acts as a transcriptional repressor.

PMID- 18827221
TI  - Somatic cell genetics for the study of NF-kappaB signaling in innate immunity.
AB  - Vertebrates have evolved acquired immunity, but to detect an infection in its
      early stages they, nonetheless, rely on Toll-like receptors (TLRs) and other
      innate immune receptors. We have performed genomewide mutagenesis screens in an
      immortalized murine cell line to study nuclear factor kappaBeta (NF-kappaB)
      signaling in the context of innate immunity. To enable metabolic and physical
      selection for alterations in NF-kappaB signaling, we equipped cells with multiple
      reporter genes. Despite the diploid nature of the cells, multiple mutants
      unresponsive to lipopolysaccharide and CpG DNA were isolated from as few as 10
      million mutagenized cells. Mutant clones may lead to the discovery of novel
      genes, and in combination with syngeneic wild-type reporter cells, they may allow
      a detailed functional analysis of NF-kappaB signaling. Compared with the use of
      whole animals in genetic screens, somatic cell genetics allows the isolation of
      genes required for innate immunity, even if these genes also have an essential
      function in development. Our discovery of an essential role for the endoplasmic
      reticulum chaperone gp96 (Grp94) in the maturation of TLRs and our work on the
      regulation of the inhibitor of nuclear factor kappaB kinase (IKK) complex by Nemo
      will be discussed in this context.

PMID- 18827222
TI  - Purinergic control of T cell activation by ATP released through pannexin-1
      hemichannels.
AB  - T cell receptor (TCR) stimulation results in the influx of Ca(2+), which is
      buffered by mitochondria and promotes adenosine triphosphate (ATP) synthesis. We
      found that ATP released from activated T cells through pannexin-1 hemichannels
      activated purinergic P2X receptors (P2XRs) to sustain mitogen-activated protein
      kinase (MAPK) signaling. P2XR antagonists, such as oxidized ATP (oATP), blunted
      MAPK activation in stimulated T cells, but did not affect the nuclear
      translocation of the transcription factor nuclear factor of activated T cells,
      thus promoting T cell anergy. In vivo administration of oATP blocked the onset of
      diabetes mediated by anti-islet TCR transgenic T cells and impaired the
      development of colitogenic T cells in inflammatory bowel disease. Thus,
      pharmacological inhibition of ATP release and signaling could be beneficial in
      treating T cell-mediated inflammatory diseases.

PMID- 18827223
TI  - Kinome siRNA screen identifies regulators of ciliogenesis and hedgehog signal
      transduction.
AB  - Disruption or improper activation of the Hedgehog (Hh) pathway is associated with
      developmental abnormalities and cancer. Although characterized in Drosophila, the
      mechanisms that mediate the Hh signal downstream of the Smoothened (Smo) seven
      transmembrane protein in vertebrates remain poorly understood. In particular, the
      Fused (Fu) kinase, which mediates Hh signaling in flies, is dispensable in
      mammals. To identify kinases that positively regulate the Hh pathway in mammals,
      we screened a mouse kinome small interfering RNA library and validated nine
      candidates that modulate Hh signaling. Among these candidates, Nek1 and Prkra did
      not directly function in the Hh pathway but exerted their effects on Hh signaling
      indirectly through a primary role in ciliogenesis. In contrast, another kinase,
      Cdc2l1, directly participated in the Hh pathway. Cdc2l1 was necessary and
      sufficient for activation of the Hh pathway, functioning downstream of Smo and
      upstream of the Glioma-associated (Gli) transcription factors. More specifically,
      Cdc2l1 interacted with the negative regulator Suppressor of Fused (Sufu) and
      relieved its inhibition on Gli, thus providing a mechanism for how Cdc2l1 might
      play a role in Hh signaling. Finally, with zebrafish as model organism, we showed
      that Cdc2l1 activated the Hh pathway in vivo. We propose that Cdc2l1 is a
      previously unrecognized member of the Hh signal transduction cascade.

PMID- 18827224
TI  - Anxiety in aging: a newly chartered territory.

PMID- 18827225
TI  - Late-life anxiety and cognitive impairment: a review.
AB  - Emerging research implicates a consistent reciprocal relationship between late
      life anxiety and cognition. Understanding this relationship may clarify
      pathophysiological substrates of cognitive impairment and why co-occurring
      anxiety and cognitive impairment relates to poorer treatment prognosis for both
      conditions. This article critically reviews evidence of more prevalent anxiety in
      cognitively impaired older adults, elevated anxiety related to poorer cognitive
      performance, and more severe anxiety symptoms predicting future cognitive
      decline. It considers pathophysiologic mediators and moderators, and the
      influence of comorbid depression or medical illness in anxiety. Identified
      directions for future research includes use of in-depth anxiety assessment
      comparing normal and mild cognitively impaired older adults and use of
      challenging neuropsychological tests to determine if specific cognitive domains
      suffer in anxious older adults.

PMID- 18827226
TI  - Pharmacotherapy for older veterans diagnosed with posttraumatic stress disorder
      in Veterans Administration.
AB  - OBJECTIVES: Despite increasing numbers of older veterans diagnosed with
      posttraumatic stress disorder (PTSD) in veterans administration (VA), limited
      research has focused on pharmacotherapy of PTSD among the elderly. DESIGN: The
      authors examined pharmacotherapy provided to patients carrying a clinical
      diagnosis of PTSD in VA. SETTING: Data on outpatients treated at VA nationally
      were utilized. PARTICIPANTS: Patients were veterans over 45 years of age
      diagnosed with PTSD in FY 2004 (N = 244,947) grouped into five age cohorts with
      patients 45-55 as the reference group. MEASURES: Psychotropic prescriptions were
      examined. Descriptive statistics and multivariable logistic regression adjusting
      for confounding characteristics, including receipt of VA service connected
      disability benefits which may create incentives to artificially maintain
      historical diagnoses, were used to identify the relationship of age to receipt of
      psychotropic medications net of these factors. All analyses were repeated using
      data only from nonservice connected veterans. RESULTS: Most older veterans
      received psychotropic medication and among these, 88.3% were prescribed
      antidepressants, 61.2% anxiolytics/sedative hypnotics, and 32.9% antipsychotics.
      A pronounced monotonic trend showed decrease use of any psychotropic medication
      and of each subclass with age. Medication use was higher among those treated in
      specialty mental health clinics than among those treated exclusively in primary
      care or medical clinics and interaction analysis of age by clinic type showed
      significantly more steeply declining use of medications with age among patients
      treated in specialty mental health clinics. Data from nonservice connected
      veterans revealed the same patterns. CONCLUSION: Diverse psychotropic medication
      classes are used to treat veterans diagnosed with PTSD in VA with declining use
      among older veterans. Medication utilization is greater in mental health clinics
      but declined more steeply with age, perhaps reflecting the greater sensitivity of
      specialists to the risks of elderly veterans. Older veterans diagnosed with PTSD
      appear to receive conservative, cautious treatment although observed patterns of
      care may reflect some degree of undertreatment.

PMID- 18827227
TI  - Generalized anxiety disorder severity scale validation in older adults.
AB  - OBJECTIVES: The Generalized Anxiety Disorder Severity Scale (GADSS) is a
      validated measure of Generalized Anxiety Disorder (GAD) symptom severity. Given
      the high prevalence of GAD in the elderly and the need for a validated scale to
      assess GAD severity in this age group, the authors examined the psychometric
      properties of the GADSS in the elderly. DESIGN, SETTING, PARTICIPANTS: The
      authors examined a sample of 134 elderly subjects (age 60 and above) who met
      diagnostic criteria for current GAD, 33 healthy elderly comparison subjects (age
      60 and above) and 186 younger subjects (age 18-60) diagnosed with GAD. RESULTS:
      The GADSS had a high internal consistency in the elderly subjects (raw Cronbach's
      alpha = 0.76). Pearson correlations showed a significant positive correlation
      between GADSS, Hamilton Rating Scale for Anxiety and Penn State Worry
      Questionnaire. Pearson correlations showed an inverse significant correlation
      between GADSS and the Medical Outcome Study SF-36. There was no correlation
      between GADSS and Mini Mental State Examination or Cumulative Illness Rating
      Scale for Geriatrics. CONCLUSIONS: The results showed a good convergent,
      concurrent, and discriminant validity of the GADSS when used for elderly with
      GAD. The authors conclude that GADSS is a valid measure of GAD symptom severity
      in older adults.

PMID- 18827228
TI  - The effect of the ApoE genotype on the association between head circumference and
      cognition.
AB  - OBJECTIVES: The aim of this study was to examine the effect of the ApoE genotype
      on the association between head circumference (HC) and cognition. DESIGN: Cross
      sectional factorial design in which Korean version of Mini Mental State
      Examination (K-MMSE) score was the dependent variable with ApoE4 status as one
      factor and HC as the other. SETTINGS: A longitudinal cohort study of the Korea
      Health 21 R&D Project Clinical Research Center for Dementia. PARTICIPANTS: A
      total of 1,902 Koreans (599 men and 1303 women) aged over 60 years. MEASUREMENTS:
      Cognitive function was assessed by the K-MMSE. HC and ApoE genotyping were
      carried out on all subjects. RESULTS: The HC was correlated with the K-MMSE
      scores (r = 0.22, df = 1,525, p < 0.01), age (r = -0.11, df = 1,521, p < 0.01),
      educational level (r = 0.30, df = 1,525, p < 0.01), height (r = 0.50, df = 1,384,
      p < 0.01), and weight (r = 0.49, df = 1,445, p < 0.01). On analysis of
      covariance, the interaction of ApoE with HC on K-MMSE was observed after
      adjusting for the age, sex, educational level, height, and weight (F = 2.527, df
      = 4, 1, 364, p = 0.039). A test of simple main effect according to ApoE status
      showed that, in the ApoE epsilon 4(-) group, the mean of K-MMSE between HC
      quintile was not different (F = 0.517, df = 4, 1,148, p = 0.723). But in the ApoE
      epsilon 4(+) group, the mean of K-MMSE between HC quintile was significantly
      different. (F = 4.163, df = 4, 211, p = 0.003). CONCLUSION: All these findings
      suggest the possibility that the presence of ApoE epsilon 4 affects cognitive
      function only when the brain reserve is low. In other words, these findings
      support the structural "brain reserve hypothesis," and the effects are more
      pronounced in genetically predisposed individuals.

PMID- 18827229
TI  - Preferences of older and younger adults with serious mental illness for
      involvement in decision-making in medical and psychiatric settings.
AB  - OBJECTIVES: There is a growing call for greater consumer participation in health
      care encounters. Prior research suggests that older age is associated with a
      greater preference for a more passive role in clinical decision-making, yet
      little is known about preferences for persons with mental illness. This pilot
      study compared preferences for involvement in decision-making between older and
      younger adults with serious mental illness. DESIGN: Cross-sectional observational
      survey. PARTICIPANTS: The authors surveyed 33 older adults (>or=50 years) and 32
      younger adults (<50 years) with serious mental illness from two mental health
      center clinics and one residential facility for their preferences on decision
      making with their psychiatrists and primary care providers. MEASUREMENTS:
      Measures included the Control Preferences Scale, the Autonomy Preference Index,
      and the Decision Self-Efficacy Scale. RESULTS: Contrary to our primary
      hypothesis, older adults reported a stronger desire for involvement in decision
      making compared with younger adults. However, both age groups were similar in
      their desire for information to aid in decision-making. The majority in both age
      groups also preferred a collaborative role with a psychiatrist for medication
      decisions, an autonomous role for decisions related to psychosocial
      interventions, and a passive role with their primary care provider. Older and
      younger adults expressed similar decision self-efficacy. CONCLUSION: Our study
      suggests that older persons with serious mental illness have a stronger desire
      for involvement in decision-making than younger consumers. Additionally, role
      preference for involvement in decision-making varies across different clinical
      decisions and for psychopharmacological versus psychosocial interventions.

PMID- 18827230
TI  - Prevalent depressive symptoms as a risk factor for conversion to mild cognitive
      impairment in an elderly Italian cohort.
AB  - OBJECTIVE: To examine the association between depressive symptoms and prevalent
      and incident mild cognitive impairment (MCI) in elderly individuals; to verify
      whether it is affected by MCI subtype. DESIGN: Prospective, population-based,
      longitudinal cohort study. SETTING: Adults >or=65 years resident in an Italian
      municipality. PARTICIPANTS: Baseline data are for 595 subjects with no cognitive
      impairment (NCI) and 72 subjects with prevalent MCI. NCI subjects underwent a 4
      year follow-up for incident MCI. MEASUREMENTS: MCI was diagnosed according to
      international criteria and classified as with (m + MCI) or without memory
      impairment (m - MCI). Baseline depressive symptoms were measured using the 30
      item Geriatric Depression Scale (GDS). Baseline use of antidepressants was also
      recorded. RESULTS: Baseline depressive symptoms (GDS >or=10) were more frequent
      in prevalent MCI cases (44.4%) than in NCI participants (18.3%). The association
      was independent of MCI subtype, antidepressant use, and sociodemographic and
      vascular risk factors. In NCI subjects, baseline depressive symptoms were also
      associated with increased risk of MCI at follow-up, but only for subjects on
      antidepressant drugs at baseline (incident cases = 72.7%) compared with those
      without depressive symptoms and not on antidepressant therapy (incident cases =
      24.0%). The association was independent of other confounders and stronger for m -
      MCI (incident cases = 45.4%) with respect to m + MCI (incident cases = 27.3%).
      CONCLUSIONS: Depressive symptoms are highly prevalent among elderly MCI subjects
      and, in cognitively normal elderly individuals, are associated with an increased
      risk of developing MCI. The association is stronger for the MCI subtype without
      memory impairment.

PMID- 18827231
TI  - Depression predicts mortality in the young old, but not in the oldest old:
      results from the Berlin Aging Study.
AB  - OBJECTIVE: There is evidence that depression in old age is associated with an
      increased mortality risk, but studies have also yielded inconclusive results.
      Possible moderators of the depression-mortality association in old age discussed
      in the literature are differences in cardiovascular morbidity, effects of
      multimorbidity, and increasing effects of subthreshold depression symptoms, such
      as minor depression and loneliness, on mortality. This study is concerned with
      the depression-mortality association in old and very old age. METHOD: Information
      about mortality status and dates of death for 497 participants of the Berlin,
      Germany, Aging Study (mean age: 85.16 years; range: 70-103 years), a population
      based, age-stratified, longitudinal study, were obtained from the Berlin,
      Germany, City Registry for up to 15 years. The authors calculated proportional
      hazard regression models to examine associations between clinical diagnosis of
      depression at baseline assessment and subsequent mortality for young-old (70-84
      years; N = 243; 68% deceased) and oldest-old participants (85+ years; N = 254;
      98% deceased). In an additional step, the authors examined whether depression
      mortality associations remained after statistically controlling for the effects
      of other mortality predictors including age, gender, education, dementia,
      cardiovascular risk factors, and other somatic diseases. RESULTS: Our analyses
      revealed strong predictive effects of depression diagnoses for mortality among
      the young old (Relative Risk = 1.60, 95% Confidence Interval = 1.13-2.26) that
      were not due to the effects of other mortality predictors (Relative Risk = 1.56,
      95% Confidence Interval = 1.09-2.22). Among the oldest old, no depression
      mortality associations were found. CONCLUSION: Depression is a significant risk
      factor for all-cause mortality in old age, yet the risk conveyed by depression
      does not hold in very old age. Possible underlying mechanisms in the very old are
      discussed.

PMID- 18827232
TI  - The pathophysiology of disc degeneration: a critical review.
AB  - The pathophysiology of intervertebral disc degeneration has been extensively
      studied. Various factors have been suggested as influencing its aetiology,
      including mechanical factors, such as compressive loading, shear stress and
      vibration, as well as ageing, genetic, systemic and toxic factors, which can lead
      to degeneration of the disc through biochemical reactions. How are these factors
      linked? What is their individual importance? There is no clear evidence
      indicating whether ageing in the presence of repetitive injury or repetitive
      injury in the absence of ageing plays a greater role in the degenerative process.
      Mechanical factors can trigger biochemical reactions which, in turn, may promote
      the normal biological changes of ageing, which can also be accelerated by genetic
      factors. Degradation of the molecular structure of the disc during ageing renders
      it more susceptible to superimposed mechanical injuries. This review supports the
      theory that degeneration of the disc has a complex multifactorial aetiology.
      Which factors initiate the events in the degenerative cascade is a question that
      remains unanswered, but most evidence points to an age-related process influenced
      primarily by mechanical and genetic factors.

PMID- 18827233
TI  - A revolution in the management of fractures of the distal radius?
AB  - The recent development of locking-plate technology has led to a potential
      revolution in the management of fractures of the distal radius. This review
      examines the evidence for pursuing anatomical restoration of the distal radius
      and the possible advantages and pitfalls of using volar locking plates to achieve
      this goal. The available evidence for adopting volar locking plates is presented
      and a number of important and, as yet unanswered, questions are highlighted.

PMID- 18827234
TI  - A history of limb amputation.
AB  - John Kirkup, the distinguished orthopaedic surgeon and archivist recently
      published a book describing the history of amputation. This annotation highlights
      the importance of this work and the particular relevance of many of its themes to
      current orthopaedic and trauma practice.

PMID- 18827235
TI  - The Metasul metal-on-metal articulation in primary total hip replacement:
      clinical and radiological results at ten years.
AB  - We report the clinical and radiological outcome at ten years of 104 primary total
      hip replacements (100 patients) using the Metasul metal-on-metal bearing. Of
      these, 52 had a cemented Stuehmer-Weber polyethylene acetabular component with a
      Metasul bearing and 52 had an uncemented Allofit acetabular component with a
      Metasul liner. A total of 15 patients (16 hips) died before their follow-up at
      ten years and three were lost to follow-up. The study group therefore comprised
      82 patients (85 hips). The mean Oxford score at ten years was 20.7 (12 to 42).
      Six of 85 hips required revision surgery. One was performed because of infection,
      one for aseptic loosening of the acetabular component and four because of
      unexplained pain. Histological examination showed an aseptic lymphocytic
      vasculitis associated lesion-type tissue response in two of these. Continued
      follow-up is advocated in order to monitor the long-term performance of the
      Metasul bearing and tissue responses to metal debris.

PMID- 18827236
TI  - The results of the titanium-coated RM acetabular component at 20 years: a long
      term follow-up of an uncemented primary total hip replacement.
AB  - In a prospective study, 93 unselected consecutive uncemented hip arthroplasties
      were performed in 80 patients using the titanium-coated RM acetabular component
      and the CLS femoral component. The mean age of the patients at operation was 52
      years (28 to 81). None were lost to follow-up. In the 23 patients who had died
      (26 hips) only one acetabular component had been revised. In the 57 living
      patients (67 hips), 13 such revisions had been performed. Of the 14 revisions,
      seven were for osteolysis, five for loosening and two for infection. Survival
      analysis of this implant showed a total probability of survival of 83% (95%
      confidence interval 73 to 90), with all revisions as the endpoint, and a
      probability of 94% (95% confidence interval 87 to 98) with revision for aseptic
      loosening as the endpoint, indicating reliable long-term fixation of the titanium
      coated RM acetabular component.

PMID- 18827237
TI  - Correlation between inclination of the acetabular component and metal ion levels
      in metal-on-metal hip resurfacing replacement.
AB  - We examined the relationships between the serum levels of chromium and cobalt
      ions and the inclination angle of the acetabular component and the level of
      activity in 214 patients implanted with a metal-on-metal resurfacing hip
      replacement. Each patient had a single resurfacing and no other metal in their
      body. All serum measurements were performed at a minimum of one year after
      operation. The inclination of the acetabular component was considered to be steep
      if the abduction angle was greater than 55 degrees. There were significantly
      higher levels of metal ions in patients with steeply-inclined components (p =
      0.002 for chromium, p = 0.003 for cobalt), but no correlation was found between
      the level of activity and the concentration of metal ions. A highly significant
      (p < 0.001) correlation with the arc of cover was found. Arcs of cover of less
      than 10 mm were correlated with a greater risk of high concentrations of serum
      metal ions. The arc of coverage was also related to the design of the component
      and to size as well as to the abduction angle of the acetabular component.
      Steeply-inclined acetabular components, with abduction angles greater than 55
      degrees, combined with a small size of component are likely to give rise to
      higher serum levels of cobalt and chromium ions. This is probably due to a
      greater risk of edge-loading.

PMID- 18827238
TI  - The surgical anatomy of the blood supply to the femoral head: description of the
      anastomosis between the medial femoral circumflex and inferior gluteal arteries
      at the hip.
AB  - The inferior gluteal artery is described in standard anatomy textbooks as
      contributing to the blood supply of the hip through an anastomosis with the
      medial femoral circumflex artery. The site(s) of the anastomosis has not been
      described previously. We undertook an injection study to define the anastomotic
      connections between these two arteries and to determine whether the inferior
      gluteal artery could supply the lateral epiphyseal arteries alone. From eight
      fresh-frozen cadaver pelvic specimens we were able to inject the vessels in 14
      hips with latex moulding compound through either the medial femoral circumflex
      artery or the inferior gluteal artery. Injected vessels around the hip were then
      carefully exposed and documented photographically. In seven of the eight
      specimens a clear anastomosis was shown between the two arteries adjacent to the
      tendon of obturator externus. The terminal vessel arising from this anastomosis
      was noted to pass directly beneath the posterior capsule of the hip before
      ascending the superior aspect of the femoral neck and terminating in the lateral
      epiphyseal vessels. At no point was the terminal vessel found between the capsule
      and the conjoined tendon. The medial femoral circumflex artery receives a direct
      supply from the inferior gluteal artery immediately before passing beneath the
      capsule of the hip. Detailed knowledge of this anatomy may help to explain the
      development of avascular necrosis after hip trauma, as well as to allow
      additional safe surgical exposure of the femoral neck and head.

PMID- 18827239
TI  - The NexGen LPS-flex to the knee prosthesis at a minimum of three years.
AB  - We carried out a prospective study to assess the clinical outcome, complications
      and survival of the NexGen Legacy posterior-stabilised-Flex total knee
      replacement (TKR) in a consecutive series of 278 knees between May 2003 and
      February 2005. Mean follow-up for 259 TKRs (98.2%) was 3.8 years (3.0 to 4.8).
      Annual follow-up showed improvement in the Knee Society scores (paired t-test, p
      < 0.05). At the last follow-up, the mean maximum flexion was 135 degrees (110
      degrees to 150 degrees). Two knees showed radiolucent lines, but revision was not
      required because the patients were asymptomatic. Revision was required in one
      case because of infection, but there were no prosthesis-related revisions. There
      were no other complications. The estimated survival rate at four years with
      revision for any reason and prosthesis-related problems was 99.6% and 100%,
      respectively. This relatively large study indicates that the legacy posterior
      stabilised-Flex design provides excellent short-term outcome but warrants ongoing
      evaluation to confirm the long-term durability and functioning of the implant.

PMID- 18827240
TI  - Total knee replacement for patients with ankylosed knees.
AB  - The purpose of this study was to determine objectively the outcome of total knee
      replacement in patients with ankylosed knees. There were 82 patients (99 knees)
      with ankylosed knees who underwent total knee replacement with a condylar
      constrained or a posterior stabilised prosthesis. Their mean age was 41.9 years
      (23 to 60) and the mean follow-up was for 8.9 years (6.6 to 14). Pre- and post
      operative data included the Hospital for Special Surgery (HSS), the Knee Society
      (KS) and the Western Ontario and McMaster University Osteoarthritis index (WOMAC)
      scores. The mean HSS, KS and WOMAC scores improved from 60, 53, and 79 pre
      operatively to 81, 85, and 37 at follow-up. These improvements were statistically
      significant (p = 0.018, 0.001 and 0.014 respectively). The mean physical, social
      and emotional WOMAC scores also improved significantly (p = 0.032, p = 0.023 and
      p < 0.001 respectively). The mean satisfaction score was 8.5 (SD 1.5). Total knee
      replacement gives good mid-term results in patients with ankylosed knees.

PMID- 18827241
TI  - Transphyseal reconstruction of the anterior cruciate ligament in prepubescent
      children.
AB  - We present the results of 17 children of Tanner stage 1 or 2 who underwent
      reconstruction of the anterior cruciate ligament between 1999 and 2006 using a
      transphyseal procedure, employing an ipsilateral four-strand hamstring graft. The
      mean age of the children was 12.1 years (9.5 to 14). The mean follow-up was 44
      months (25 to 100). Survival of the graft, the functional outcome and
      complications were recorded. There was one re-rupture following another injury.
      Of the remaining patients, all had good or excellent results and a normal
      International Knee Documentation Committee score. The mean post-operative Lysholm
      score was 97.5 (SD 2.6) and the mean Tegner activity scale was 7.9 (SD 1.4). One
      patient had a mild valgus deformity which caused no functional disturbance. No
      other abnormality or discrepancy of leg length was seen. Measurements with a
      KT1000 arthrometer showed no significant difference between the normal and the
      operated legs. In this small series, transphyseal reconstruction of the anterior
      cruciate ligament appeared to be safe in these young children.

PMID- 18827242
TI  - Concomitant reconstruction of the medial collateral and posterior oblique
      ligaments for medial instability of the knee.
AB  - We present the operative technique and clinical results of concomitant
      reconstruction of the medial collateral ligament (MCL) and the posterior oblique
      ligament for medial instability of the knee using autogenous semitendinosus
      tendon with preservation of the tibial attachment. The semitendinosus tendon
      graft between the screw on the medial epicondyle and the tibial attachment of the
      graft was overlapped by the MCL, while the graft between the screw and the
      insertion of the direct head of the semimembranosus tendon was overlapped by the
      central arm of the posterior oblique ligament. Assessment was by stress
      radiograph and the Lysholm knee scoring scale. After a mean follow-up of 52.6
      months (25 to 92), the medial joint opening of the knee was within 2 mm in 22 of
      24 patients. The mean Lysholm score was 91.9 (80 to 100). Concomitant
      reconstruction of the MCL and posterior oblique ligament using autogenous
      semitendinosus tendon provides a good solution to medial instability.

PMID- 18827243
TI  - Endoscopically-assisted single-bundle posterior cruciate ligament reconstruction:
      results at minimum ten-year follow-up.
AB  - We evaluated the long-term outcome of isolated endoscopically-assisted posterior
      cruciate ligament reconstruction in 26 patients using hamstring tendon autografts
      after failure of conservative management. At ten years after surgery the mean
      International Knee Documentation Committee subjective knee score was 87 (SD 14)
      of a possible 100 points. Regular participation in moderate to strenuous
      activities was possible for only seven patients pre-operatively; this increased
      to 23 patients post-operatively. The mean Lysholm score improved from 64 (SD 15)
      to 90 (SD 14) at ten years (p = 0.001). At ten years endoscopic reconstruction of
      the posterior cruciate ligament with hamstring tendon autograft is effective in
      reducing knee symptoms. Of the series, 22 patients underwent radiological
      assessment for the development of osteoarthritis using the Kellgren-Lawrence
      grading scale. In four patients, grade 2 changes with loss of joint space was
      observed and another four patients showed osteophyte formation with moderate
      joint space narrowing (grade 3). These findings compared favourably with non
      operatively managed injuries of the posterior cruciate ligament. This procedure
      for symptomatic patients with posterior cruciate ligament laxity who have failed
      conservative management offers good results.

PMID- 18827244
TI  - A finite-element analysis study of the metatarsophalangeal joint of the hallux
      rigidus.
AB  - Hallux rigidus was first described in 1887. Many aetiological factors have been
      postulated, but none has been supported by scientific evidence. We have examined
      the static and dynamic imbalances in the first metatarsophalangeal joint which we
      postulated could be the cause of this condition. We performed a finite-element
      analysis study on a male subject and calculated a mathematical model of the joint
      when subjected to both normal and abnormal physiological loads. The results gave
      statistically significant evidence for an increase in tension of the plantar
      fascia as the cause of abnormal stress on the articular cartilage rather than
      mismatch of the articular surfaces or subclinical muscle contractures. Our study
      indicated a clinical potential cause of hallux rigidus and challenged the many
      aetiological theories. It could influence the choice of surgical procedure for
      the treatment of early grades of hallux rigidus.

PMID- 18827245
TI  - Mid-term clinical and sonographic outcome of arthroscopic repair of the rotator
      cuff.
AB  - We have conducted a prospective study to assess the mid-term clinical results
      following arthroscopic repair of the rotator cuff. Patients were evaluated using
      the Constant score, subjective satisfaction levels and post-operative ultrasound
      scans. Of 115 consecutive patients who underwent arthroscopic repair of the
      rotator cuff at our institution, 102 were available for follow-up. The mean
      period of follow-up was for 35.8 months (24 to 73). The mean age of the patients
      was 57.3 years (23 to 78). There were 18 small (< or = 1 cm in diameter), 44
      medium (1 cm to 3 cm in diameter), 34 large (3 cm to 5 cm in diameter) and six
      massive (> 5 cm in diameter) tears. There was a statistically significant
      increase in the size of the tear with increasing age (p = 0.0048). The mean pre
      operative Constant score was 41.4 points (95% confidence interval, 37.9 to 44.9),
      which improved to 84.5 (95% confidence interval, 82.2 to 86.9). A significant
      inverse association (p = 0.0074), was observed between the size of the tear and
      the post-operative Constant score, with patients having smaller tears attaining
      higher Constant scores after repair. Post-operatively, 80 patients (78.4%) were
      able to resume their occupations and 84 (82.4%) returned to their pre-injury
      leisure activities. Only eight (7.8%) of 102 patients were not satisfied with the
      outcome. Recurrent tears were detected by ultrasound in 19 (18.6%) patients, and
      were generally smaller than the original ones. Patients with recurrent tears
      experienced a mean improvement of 31.6 points (95% confidence interval, 23.6 to
      39.6) in their post-operative Constant scores. Those with intact repairs had
      significantly improved (p < 0.0001) Constant scores (mean improvement 46.3
      points, 95% confidence interval, 41.9 to 50.6). Patient satisfaction was high in
      94 cases (92%), irrespective of the outcome of the Constant score. Recurrent
      tears appear to be linked to age-related degeneration. Arthroscopic repair of the
      rotator cuff leads to high rates of satisfaction (92%) and good functional
      results, albeit with a recurrence rate of 18.6% (19 of 102).

PMID- 18827246
TI  - Neurolysis of the ulnar nerve for neuropathy following total elbow replacement.
AB  - Ulnar neuropathy presents as a complication in 5% to 10% of total elbow
      replacements, but subsequent ulnar neurolysis is rarely performed. Little
      information is available on the surgical management of persistent ulnar
      neuropathy after elbow replacement. We describe our experience with the surgical
      management of this problem. Of 1607 total elbow replacements performed at our
      institution between January 1969 and December 2004, eight patients (0.5%) had a
      further operation for persistent or progressive ulnar neuropathy. At a mean
      follow-up of 9.2 years (3.1 to 21.7) six were clinically improved and satisfied
      with their outcome, although, only four had complete recovery. When transposition
      was performed on a previously untransposed nerve the rate of recovery was 75%,
      but this was reduced to 25% if the nerve had been transposed at the time of the
      replacement.

PMID- 18827247
TI  - Posterior lumbar interbody fusion for adult isthmic spondylolisthesis: a
      comparison of fusion with one or two cages.
AB  - Between March 2000 and February 2006, we carried out a prospective study of 100
      patients with a low-grade isthmic spondylolisthesis (Meyerding grade II or
      below), who were randomised to receive a single-level and instrumented posterior
      lumbar interbody fusion with either one or two cages. The minimum follow-up was
      for two years. At this stage 91 patients were available for review. A total of 47
      patients received one cage (group 1) and 44 two cages (group 2). The clinical and
      radiological outcomes of the two groups were compared. There were no significant
      differences between the two groups in terms of post-operative pain, Oswestry
      Disability Score, clinical results, complication rate, percentage of post
      operative slip, anterior fusion rate or posterior fusion rate. On the other hand,
      the mean operating time was 144 minutes (100 to 240) for patients in group 1 and
      167 minutes (110 to 270) for those in group 2 (p = 0.0002). The mean blood loss
      up to the end of the first post-operative day was 756 ml (510 to 1440) in group 1
      and 817 ml (620 to 1730) in group 2 (p < 0.0001). Our results suggest that an
      instrumented posterior lumbar interbody fusion performed with either one or two
      cages in addition to a bone graft around the cage has a low rate of complications
      and a high fusion rate. The clinical outcomes were good in most cases, regardless
      of whether one or two cages had been used.

PMID- 18827248
TI  - Early mortality after surgical fixation of hip fractures in the elderly: an
      analysis of data from the scottish hip fracture audit.
AB  - We investigated the relationship between a number of patient and management
      variables and mortality after surgery for fracture of the hip. Data relating to
      18,817 patients were obtained from the Scottish Hip Fracture Audit database. We
      divided variables into two categories, depending on whether they were case-mix
      (age; gender; fracture type; pre-fracture residence; pre-fracture mobility and
      ASA scores) or management variables (time from fracture to surgery; time from
      admission to surgery; grade of surgical and anaesthetic staff undertaking the
      procedure and anaesthetic technique). Multivariate logistic regression analysis
      showed that all case-mix variables were strongly associated with post-operative
      mortality, even when controlling for the effects of the remaining variables.
      Inclusion of the management variables into the case-mix base regression model
      provided no significant improvement to the model. Patient case-mix variables have
      the most significant effect on post-operative mortality and unfortunately such
      variables cannot be modified by pre-operative medical interventions.

PMID- 18827249
TI  - Prognostic factors and outcome of treatment in Perthes' disease: a prospective
      study of 368 patients with five-year follow-up.
AB  - This nationwide prospective study was designed to determine prognostic factors
      and evaluate the outcome of different treatments of Perthes' disease. A total of
      28 hospitals in Norway were instructed to report all new cases of Perthes'
      disease over a period of five years and 425 patients were reported and followed
      for five years. Of these, 368 with unilateral disease were included in the
      present study. The hips were classified radiologically according to a modified
      two-group Catterall classification and the lateral pillar classification. A total
      of 358 patients (97%) attended the five-year follow-up, when a modified three
      group Stulberg classification was used as a radiological outcome measure. For
      patients over six years of age at diagnosis and with more than 50% necrosis of
      the femoral head (152 patients), the surgeons at the different hospitals had
      chosen one of three methods of treatment: physiotherapy (55 patients), the
      Scottish Rite abduction orthosis (26), and proximal femoral varus osteotomy (71).
      Of these hips, 146 (96%) were available for the five-year follow-up. The
      strongest predictor of outcome was femoral head involvement of more or less than
      50% (odds ratio (OR) = 7.76, 95% confidence interval (CI) 2.82 to 21.37),
      followed by age at diagnosis (OR = 0.98, 95% CI 0.92 to 0.99) and the lateral
      pillar classification (OR = 0.62, 95% CI 0.40 to 0.98). In children over six
      years at diagnosis with more than 50% of femoral head necrosis, proximal femoral
      varus osteotomy gave a significantly better outcome than orthosis (p = 0.001) or
      physiotherapy (p = 0.001). There was no significant difference between the
      physiotherapy and orthosis groups (p = 0.36), and we found no difference in
      outcome after any of the treatments in children under six years (p = 0.73). We
      recommend proximal femoral varus osteotomy in children aged six years and over at
      the time of diagnosis with hips having more than 50% femoral head necrosis. The
      abduction orthosis should be abandoned in Perthes' disease.

PMID- 18827250
TI  - Proximal femoral geometry in cerebral palsy: a population-based cross-sectional
      study.
AB  - There is much debate about the nature and extent of deformities in the proximal
      femur in children with cerebral palsy. Most authorities accept that increased
      femoral anteversion is common, but its incidence, severity and clinical
      significance are less clear. Coxa valga is more controversial and many
      authorities state that it is a radiological artefact rather than a true
      deformity. We measured femoral anteversion clinically and the neck-shaft angle
      radiologically in 292 children with cerebral palsy. This represented 78% of a
      large, population-based cohort of children with cerebral palsy which included all
      motor types, topographical distributions and functional levels as determined by
      the gross motor function classification system. The mean femoral neck anteversion
      was 36.5 degrees (11 degrees to 67.5 degrees) and the mean neck-shaft angle 147.5
      degrees (130 degrees to 178 degrees). These were both increased compared with
      values in normally developing children. The mean femoral neck anteversion was
      30.4 degrees (11 degrees to 50 degrees) at gross motor function classification
      system level I, 35.5 degrees (8 degrees to 65 degrees ) at level II and then
      plateaued at approximately 40.0 degrees (25 degrees to 67.5 degrees) at levels
      III, IV and V. The mean neck-shaft angle increased in a step-wise manner from
      135.9 degrees (130 degrees to 145 degrees) at gross motor function classification
      system level I to 163.0 degrees (151 degrees to 178 degrees) at level V. The
      migration percentage increased in a similar pattern and was closely related to
      femoral deformity. Based on these findings we believe that displacement of the
      hip in patients with cerebral palsy can be explained mainly by the abnormal shape
      of the proximal femur, as a result of delayed walking, limited walking or
      inability to walk. This has clinical implications for the management of hip
      displacement in children with cerebral palsy.

PMID- 18827251
TI  - Non-operative management of femoral neuropathy secondary to a traumatic iliacus
      haematoma in an adolescent.
AB  - Iliacus haematoma is a relatively rare condition, which may cause a local
      compressive neuropathy. It is usually diagnosed in adults with haemophilia or
      those on anticoagulation treatment and may occur after trauma. We present the
      case of a healthy 15-year-old boy with a femoral neuropathy due to an iliacus
      haematoma which resolved following conservative treatment.

PMID- 18827252
TI  - Open medial dislocation of the ankle without fracture.
AB  - A 20-year-old man sustained an open medial dislocation of the ankle without an
      associated fracture after a low-energy inversion injury. Prompt debridement and
      reduction with primary wound closure of the skin were performed without suture of
      the capsule. Immobilisation in a non-weight-bearing cast for 30 days followed by
      ankle bracing for two weeks and subsequent physiotherapy, produced full
      functional recovery by three months. At follow-up at one year there was a full
      range of pain-free movement, although the radiographs and MR scan showed early
      post-traumatic degenerative change at the medial aspect of the tibiotalar and the
      calcaneocuboid joints.

PMID- 18827253
TI  - A comparison of single-versus double-row suture anchor techniques in a simulated
      repair of the rotator cuff: an experimental study in rabbits.
AB  - We compared time-dependent changes in the biomechanical properties of single-and
      double-row repair of a simulated acute tear of the rotator cuff in rabbits to
      determine the effect of the fixation techniques on the healing process. A tear of
      the supraspinatus tendon was created in 80 rabbits which were separated into two
      equal groups. A single-row repair with two suture anchors was conducted in group
      1 and a double-row repair with four suture anchors in group 2. A total of ten
      intact contralateral shoulder joints was used as a control group. Biomechanical
      testing was performed immediately post-operatively and at four and eight weeks,
      and histological analysis at four and eight weeks. The mean load to failure in
      group 2 animals was greater than in group 1, but both groups remained lower than
      the control group at all intervals. Histological analysis showed similar healing
      properties at four and eight weeks in both groups, but a significantly larger
      number of healed tendon-bone interfaces were identified in group 2 than in group
      1 at eight weeks (p < 0.012). The ultimate load to failure increased with the
      number of suture anchors used immediately post-operatively, and at four and eight
      weeks. The increased load to failure at eight weeks seemed to be related to the
      increase in the surface area of healed tendon-to-bone in the double-row repair
      group.

PMID- 18827254
TI  - In vivo local administration of osteogenic protein-1 increases structural
      properties of the overstretched anterior cruciate ligament with partial
      midsubstance laceration: a biomechanical study in rabbits.
AB  - We report the effects of local administration of osteogenic protein-1 on the
      biomechanical properties of the overstretched anterior cruciate ligament in an
      animal model. An injury in the anterior cruciate ligament was created in 45
      rabbits. They were divided into three equal groups. In group 1, no treatment was
      applied, in group II, phosphate-buffered saline was applied around the injured
      ligament, and in group III, 12.5 microg of osteogenic protein-1 mixed with
      phosphate-buffered saline was applied around the injured ligament. A control
      group of 15 rabbits was assembled from randomly-selected injured knees from among
      the first three groups. Each rabbit was killed at 12 weeks. The maximum load and
      stiffness of the anterior cruciate ligament was found to be significantly greater
      in group III than either group 1 (p = 0.002, p = 0.014) or group II (p = 0.032, p
      = 0.025). The tensile strength and the tangent modulus of fascicles from the
      ligament were also significantly greater in group III than either group I (p =
      0.002, p = 0.0174) or II (p = 0.005, p = 0.022). The application of osteogenic
      protein-1 enhanced the healing in the injured anterior cruciate ligament, but
      compared with the control group the treated ligament remained lengthened. The
      administration of osteogenic protein-1 may have a therapeutic role in treating
      the overstretched anterior cruciate ligament.

PMID- 18827255
TI  - Factor XI mutation and the origin of Ashkenazi Jews.

PMID- 18827257
TI  - Efficacy of cyclosporine as a single agent therapy in chronic idiopathic
      thrombocytopenic purpura.

PMID- 18827259
TI  - Reply to: Non-Hodgkin's lymphoma and residential proximity to toxic industrial
      waste in southern Israel. Haematologica 2005; 90:1709-10.

PMID- 18827260
TI  - New and old players in the hepcidin pathway.

PMID- 18827261
TI  - Novel thrombopoietic agents: a new era for management of patients with
      thrombocytopenia.

PMID- 18827262
TI  - Allogeneic hematopoietic stem cell transplantation for myelofibrosis.

PMID- 18827263
TI  - Adoptive T-cell therapy for malignant disorders.

PMID- 18827264
TI  - Hemojuvelin N-terminal mutants reach the plasma membrane but do not activate the
      hepcidin response.
AB  - BACKGROUND: Hemojuvelin is a glycosylphosphatidylinositol-anchored protein,
      expressed in liver, skeletal muscle and heart. As a co-receptor of bone
      morphogenetic protein, membrane hemojuvelin positively modulates the iron
      regulator hepcidin. Mutations of the gene encoding for hemojuvelin cause juvenile
      hemochromatosis, characterized by hepcidin deficiency and severe iron overload.
      We have previously shown that several hemojuvelin variants do not efficiently
      reach the plasma membrane, whereas a few N-terminal mutants localize to the
      plasma membrane. DESIGN AND METHODS: We studied hemojuvelin mutants of N-terminus
      (C80R, S85P, G99V, DeltaRGD) and GDPH-consensus site for autoproteolysis (A168D,
      F170S, D172E) transiently expressed in HeLa cells, using electron microscopy,
      morphometric analysis and binding assays at different time points. Hepcidin
      activation by wild-type and mutant forms of hemojuvelin was assessed in Hep3B
      cells transfected with a hepcidin-promoter luciferase-reporter construct.
      RESULTS: S85P, G99V and DeltaRGD were localized to plasma membrane 36 hours after
      transfection, but less efficiently exported than the wild-type protein at earlier
      (24-30 hours) times. Morphometric analysis clearly documented delayed export and
      endoplasmic reticulum retention of G99V. C80R was exported without delay. GDPH
      variants were partially retained in the endoplasmic reticulum and Golgi
      apparatus, but showed impaired plasma membrane localization. In the hepcidin
      promoter assay only wild type hemojuvelin was able to activate hepcidin.
      CONCLUSIONS: The delayed export and retention in the endoplasmic reticulum of
      some N-terminal mutants could contribute to the pathogenesis of juvenile
      hemochromatosis, reducing a prompt response of bone morphogenetic protein.
      However, independently of their plasma membrane export, all hemojuvelin mutants
      tested showed no or minimal hepcidin activation.

PMID- 18827265
TI  - Gene encoding Duffy antigen/receptor for chemokines is associated with asthma and
      IgE in three populations.
AB  - RATIONALE: Asthma prevalence and severity are high among underserved minorities,
      including those of African descent. The Duffy antigen/receptor for chemokines is
      the receptor for Plasmodium vivax on erythrocytes and functions as a chemokine
      clearing receptor. Unlike European populations, decreased expression of the
      receptor on erythrocytes is common among populations of African descent, and
      results from a functional T-46C polymorphism (rs2814778) in the promoter. This
      variant provides an evolutionary advantage in malaria-endemic regions, because
      Duffy antigen/receptor for chemokines-negative erythrocytes are more resistant to
      infection by P. vivax. OBJECTIVES: To determine the role of the rs2814778
      polymorphism in asthma and atopy as measured by total serum IgE levels among four
      populations of African descent (African Caribbean, African American, Brazilian,
      and Colombian) and a European American population. METHODS: Family-based
      association tests were performed in each of the five populations to test for
      association between the rs2814778 polymorphism and asthma or total IgE
      concentration. MEASUREMENTS AND MAIN RESULTS: Asthma was significantly associated
      with the rs2814778 polymorphism in the African Caribbean, Colombian, and
      Brazilian families (P < 0.05). High total IgE levels were associated with this
      variant in African Caribbean and Colombian families (P < 0.05). The variant
      allele was not polymorphic among European Americans. CONCLUSIONS: Susceptibility
      to asthma and atopy among certain populations of African descent is influenced by
      a functional polymorphism in the gene encoding Duffy antigen/receptor for
      chemokines. This genetic variant, which confers resistance to malarial parasitic
      infection, may also partially explain ethnic differences in morbidity of asthma.

PMID- 18827266
TI  - Impact of neurofibromatosis type 1 on school performance.
AB  - School functioning of 86 Dutch neurofibromatosis type 1 children (7-17 years)
      using teacher questionnaires was analyzed to determine the impact of
      neurofibromatosis type 1 on school performance. In all, 75% of the
      neurofibromatosis type 1 children performed more than 1 standard deviation below
      grade peers in at least one of the domains of spelling, mathematics, technical
      reading or comprehensive reading. Furthermore, neurofibromatosis type 1 children
      had a 4-fold increased risk for attending special education and a 6-fold
      increased risk for receiving remedial teaching for learning, behavior, speech, or
      motor problems. Children without apparent learning disabilities still frequently
      displayed neuropsychological deficits. Only 10% of the children did not show any
      school-functioning problems. Finally, it was found that the clinical severity of
      neurofibromatosis type 1 correlated with the cognitive deficits. Taken together,
      it was shown that neurofibromatosis type 1 has profound impact on school
      performance. Awareness of these problems may facilitate timely recognition and
      appropriate support.

PMID- 18827267
TI  - Infected intraparenchymal dermoids: an underestimated entity.
AB  - Infection secondary to a dermal sinus most commonly occurs in the form of
      cutaneous, epidural, or subdural abscesses. Rarely, it can result in an
      intramedullary abscess as a result of a dermal sinus. This study presents a
      clinicoradiological profile of 19 cases harboring abscesses within the dermoids
      and highlights the importance of dermal sinus acting as a pathway for infections
      to enter the nervous system. Emergent exploration, pus drainage, and minimal
      abscess wall excision along with prolonged antibiotic administration remained the
      management of choice in all cases. Methicillin-sensitive Staphylococcus aureus
      was the commonest offending organism. In all, 7 patients recovered to normal
      neurological status, 5 showed no improvement, and 7 improved partially.
      Improvement in motor power was noted, albeit partially, but bladder functions
      failed to recover even at long-term follow-up. Even when such infective
      complications of dermal sinuses are rare, these are potentially serious and
      disabling.

PMID- 18827268
TI  - Validation of the presence of comorbidities in a Danish clinical cohort of
      children with Tourette syndrome.
AB  - Tourette syndrome (TS) is characterized by the presence of motor and vocal tics
      and is often accompanied by comorbid symptoms. We assessed the frequency of the
      comorbid symptoms obsessive-compulsive disorder obsessive-compulsive disorder,
      attention-deficit hyperactivity disorder (ADHD), rage attacks, sleeping
      disturbances, and depressive symptoms in a Danish clinical cohort of 314 children
      with TS using validated diagnostic instruments. For the assessment of symptoms of
      seasonal affective disorder and stuttering, we used a nonvalidated systematic
      interview. In total, only 10.2% of the children did not have any comorbid
      symptoms at all. If ADHD and/or obsessive-compulsive disorder were present, the
      rates of the comorbidities rage, symptoms of seasonal affective disorder, sleep
      disturbances, and depressive symptoms were significantly higher than if ADHD
      and/or obsessive-compulsive disorder were absent. The most severe tics were found
      in the group for which both ADHD and obsessive-compulsive disorder were present.
      Furthermore, there was a tendency toward more severe tics if other comorbid
      symptoms were present.

PMID- 18827269
TI  - Use of intravenous tissue plasminogen activator in a 16-year-old patient with
      basilar occlusion.
AB  - Intravenous tissue plasminogen activator (t-PA) is currently approved by the US
      Food and Drug Administration (FDA) for the treatment of ischemic stroke in
      patients > 18 years of age who present within 3 hours of stroke onset and meet
      certain criteria. We report a case of a 16-year-old, previously healthy female
      who presented with a basilar artery occlusion and pontine ischemic stroke. She
      was treated with intravenous t-PA approximately 4 hours after the onset of
      symptoms. The patient demonstrated a remarkable recovery 6 hours after onset of
      her symptoms and had minimal deficits on discharge from the hospital 1 week
      later. She was found to have a lupus anticoagulant and was heterozygous for the
      prothrombin gene G2010A mutation. These were likely contributing causes for her
      stroke. She was also homozygous for plasminogen activator inhibitor 1 (PAI-1)
      4G/4G, which at present is a controversial stroke risk factor.

PMID- 18827270
TI  - Divergent ependymal tumor (ependymoblastoma/anaplastic ependymoma) of the
      posterior fossa: an uncommon case observed in a child.
AB  - We report a divergent ependymal tumor of the posterior fossa
      (ependymoblastoma/anaplastic ependymoma) observed in an 8-year-old boy. The tumor
      showed the histological pattern typical of an ependymoblastoma (tubular-papillary
      fetaloid architecture with stratification of the tumor cells) next to areas in
      which findings typical of an anaplastic ependymoma were detected. The
      immunohistochemical study confirmed our diagnostic suspicion, allowing us to
      establish a differential diagnosis with other entities such as medulloblastoma,
      medulloepithelioma, atypical rhabdoid/teratoid tumor, or metastases.

PMID- 18827271
TI  - Clinical observation of self-injurious behavior correlated with changes in scalp
      morphology in a child with congenital hydrocephalus.
AB  - We report the case of a 12-year-old girl born with cerebral dysgenesis and
      congenital hydrocephalus first shunted shortly after birth. She had severe tissue
      damaging self-injurious behavior, profound mental retardation, quadriparesis, as
      well as multiple cranial anomalies including turricephaly. After stage 1 cranial
      remodeling, a bone window was left pending second stage remodeling. Episodic
      changes in fluctuation of the scalp overlying the bone window were easily
      observed. During the course of a behavioral assessment for her self-injury, it
      was observed that the overall frequency of occurrence of self-injury increased
      significantly (P < .01) when the scalp was protruding and bulging compared with
      when the scalp was flush with the skull table. Periods of increased scalp
      protrusion were also associated with higher scores on a pain scale developed for
      children with communicative impairments associated with severe neurological
      impairment. After shunt replacement, there was remarkable improvement in
      functional status and decreased episodic self-injury.

PMID- 18827272
TI  - Acute epidural hematoma with infarction of the right hemisphere in a 5-month-old
      child: case report with a long-term follow-up and a review of the literature.
AB  - Two hours after a fall, a 5-month-old girl was admitted to our hospital because
      of an extended galea hematoma and restlessness. Five hours after the trauma, a
      left hemiparesis developed. The child became drowsy. The hematocrit had fallen to
      7.1 g/dL. Cranial computerized tomography disclosed a huge frontoparietal
      epidural hematoma on the right side and a hypodensity in the territories of the
      middle and posterior cerebral arteries. Immediately before surgery, the right
      pupil dilated. After evacuation of the epidural hematoma and ligation of the
      middle meningeal artery, the girl recovered satisfactorily. Nevertheless,
      magnetic resonance imaging showed a vast defect zone in the territories of the
      right middle and posterior cerebral arteries. Six weeks after the injury, the
      visual-evoked potentials were unavailable on both sides. Four years after the
      accident, visual assessment revealed normal acuity and stereopsis. Cognitive and
      neuromotor development were undisturbed and appropriate to the age.

PMID- 18827273
TI  - Epstein-Barr virus-associated meningoencephalomyelitis: intrathecal reactivation
      of the virus in an immunocompetent child.
AB  - Neurologic complications, including meningoencephalitis, transverse myelitis, and
      peripheral neuropathy, have been reported in patients with acute infectious
      mononucleosis. Chronic active Epstein-Barr virus and human immunodeficiency virus
      infections occasionally induce central nervous system lymphoma. On the other
      hand, central nervous system disease alone associated with Epstein-Barr virus
      rarely occurs in previously healthy individuals. A 15-year-old girl who developed
      acute disseminated encephalomyelitis-like disease presenting fever, anuresis,
      diplopia, and muscle weakness is described here. Clinical and neuroimaging
      studies led to the diagnosis of encephalomyelitis. Despite the absence of
      infectious mononucleosis-like symptoms, anti-Epstein-Barr virus antibody titers
      in serum and cerebrospinal fluid showed the virus reactivation. The copy number
      of Epstein-Barr virus DNA increased in cerebrospinal fluid but not in peripheral
      blood. Ganciclovir and repeated methyl-prednisolone pulse therapy resulted in
      complete resolution. Central nervous system disease on the limited intrathecal
      reactivation of Epstein-Barr virus in immunocompetent children should be
      differentiated from acute disseminated encephalomyelitis.

PMID- 18827274
TI  - Does ghrelin really increase in epileptic children treated with valproate?

PMID- 18827275
TI  - Correspondence on "Childhood epilepsy with occipital paroxysms: difficulties in
      distinct segregation into either the early-onset or late-onset epilepsy
      subtypes".

PMID- 18827277
TI  - Correct definition and reference of the term "status gelasticus".

PMID- 18827280
TI  - The appalling Poling saga.

PMID- 18827282
TI  - "Worshiping false idols: the impact factor dilemma": correcting the record.

PMID- 18827283
TI  - Effects of acceptor composition and mechanism of ABCG1-mediated cellular free
      cholesterol efflux.
AB  - Among the known mechanisms of reverse cholesterol transport (RCT), ATP binding
      cassette transporter G1 (ABCG1)-mediated free cholesterol (FC) transport is the
      most recent and least studied. Here, we have characterized the efficiencies of
      different acceptors using baby hamster kidney (BHK) cells transfected with human
      ABCG1 cDNA, which is inducible upon treatment with mifepristone. When normalized
      on particle number and particle surface area, the acceptor efficiency for FC
      efflux was as follows: small unilamellar vesicles (SUV)>LDL>reconstituted
      HDL>HDL(2) = HDL(3). Based on phospholipid content, the order was reversed. ABCG1
      also mediated phospholipid efflux to human serum and HDL(3). ABCG1-mediated FC
      efflux correlated significantly with a number of HDL subfractions and components
      in serum collected from 25 normolipidemic individuals: apolipoprotein A-II (apoA
      II) (r(2) = 0.7), apolipoprotein A-I (apoA-I) (r(2) = 0.5), HDL-C (r(2) = 0.4),
      HDL-PL (r(2) = 0.4), alpha-2 HDL (r(2) = 0.4), and prebeta HDL (r(2) = 0.2).
      ABCG1 did not enhance influx of FC or cholesteryl oleyl ether (COE) when cells
      were incubated with radiolabeled HDL(3). ABCG1 expression did not increase the
      association of HDL(3) with cells. Compared with control cells, ABCG1 expression
      significantly increased the FC pool available for efflux and the rate constant
      for efflux. In conclusion, composition and particle size determine the acceptor
      efficiency for ABCG1-mediated efflux. ABCG1 increases cell membrane FC pools and
      changes its rate of desorption into the aqueous phase without enhancing the
      association with the acceptor.

PMID- 18827284
TI  - 2-Bromopalmitate and 2-(2-hydroxy-5-nitro-benzylidene)-benzo[b]thiophen-3-one
      inhibit DHHC-mediated palmitoylation in vitro.
AB  - Pharmacologic approaches to studying palmitoylation are limited by the lack of
      specific inhibitors. Recently, screens have revealed five chemical classes of
      small molecules that inhibit cellular processes associated with palmitoylation
      (Ducker, C. E., L. K. Griffel, R. A. Smith, S. N. Keller, Y. Zhuang, Z. Xia, J.
      D. Diller, and C. D. Smith. 2006. Discovery and characterization of inhibitors of
      human palmitoyl acyltransferases. Mol. Cancer Ther. 5: 1647-1659). Compounds that
      selectively inhibited palmitoylation of N-myristoylated vs. farnesylated peptides
      were identified in assays of palmitoyltransferase activity using cell membranes.
      Palmitoylation is catalyzed by a family of enzymes that share a conserved DHHC
      (Asp-His-His-Cys) cysteine-rich domain. In this study, we evaluated the ability
      of these inhibitors to reduce DHHC-mediated palmitoylation using purified enzymes
      and protein substrates. Human DHHC2 and yeast Pfa3 were assayed with their
      respective N-myristoylated substrates, Lck and Vac8. Human DHHC9/GCP16 and yeast
      Erf2/Erf4 were tested using farnesylated Ras proteins. Surprisingly, all four
      enzymes showed a similar profile of inhibition. Only one of the novel compounds,
      2-(2-hydroxy-5-nitro-benzylidene)-benzo[b]thiophen-3-one [Compound V (CV)], and 2
      bromopalmitate (2BP) inhibited the palmitoyltransferase activity of all DHHC
      proteins tested. Hence, the reported potency and selectivity of these compounds
      were not recapitulated with purified enzymes and their cognate lipidated
      substrates. Further characterization revealed both compounds blocked DHHC enzyme
      autoacylation and displayed slow, time-dependent inhibition but differed with
      respect to reversibility. Inhibition of palmitoyltransferase activity by CV was
      reversible, whereas 2BP inhibition was irreversible.

PMID- 18827285
TI  - Melatonin and its agonists: an update.
AB  - The pineal hormone melatonin is able to shift the timing of circadian rhythms,
      including the sleep-wake cycle, and to promote sleep. Melatonin agonists with
      similar properties have therapeutic potential for the treatment of circadian
      rhythm sleep disorders. Depression is specifically targeted by agomelatine, which
      is also a serotonin-2C (5-HT(2C)) antagonist.

PMID- 18827286
TI  - Pros and cons of online cognitive-behavioural therapy.
AB  - Online cognitive-behavioural therapy (CBT) for depression has the potential to
      serve as an important addition to the care of people with mild to moderate
      depression. Although some studies show promising results, the need for proper
      diagnoses and human guidance must be considered when interpreting the modest
      effects found in studies with little or no guidance from a therapist.

PMID- 18827287
TI  - Relationship between gross domestic product and duration of untreated psychosis
      in low- and middle-income countries.
AB  - BACKGROUND: The duration of untreated psychosis (DUP), the period between the
      first onset of psychotic symptoms and treatment, has an important influence on
      the outcome of schizophrenia. AIMS: To compare the published studies of DUP in
      low- and middle-income (LAMI) countries with the DUP of high-income countries,
      and examine a possible association between DUP and per capita income. METHOD: We
      used six search strategies to locate studies of the DUP from LAMI countries
      published between January 1975 and January 2008. We then examined the
      relationship between DUP and measures of economic activity, which was assessed
      using the LAMI classification of countries and gross domestic product (GDP)
      purchasing power parity. RESULTS: The average mean DUP in studies from LAMI
      countries was 125.0 weeks compared with 63.4 weeks in studies from high-income
      countries (P=0.012). Within the studies from LAMI countries, mean DUP fell by 6
      weeks for every $1000 of GDP purchasing power parity. CONCLUSIONS: There appears
      to be an inverse relationship between income and DUP in LAMI countries. The cost
      of treatment is an impediment to care and subsidised antipsychotic medication
      would improve the access to treatment and the outcome of psychotic illness in
      LAMI countries.

PMID- 18827290
TI  - Neurotoxic effects of ecstasy on the thalamus.
AB  - BACKGROUND: Neurotoxic effects of ecstasy have been reported, although it remains
      unclear whether effects can be attributed to ecstasy, other recreational drugs or
      a combination of these. AIMS: To assess specific/independent neurotoxic effects
      of heavy ecstasy use and contributions of amphetamine, cocaine and cannabis as
      part of The Netherlands XTC Toxicity (NeXT) study. METHOD: Effects of ecstasy and
      other substances were assessed with (1)H-magnetic resonance spectroscopy,
      diffusion tensor imaging, perfusion weighted imaging and [(123)I]2beta
      carbomethoxy-3beta-(4-iodophenyl)-tropane ([(123)I]beta-CIT) single photon
      emission computed tomography (serotonin transporters) in a sample (n=71) with
      broad variation in drug use, using multiple regression analyses. RESULTS: Ecstasy
      showed specific effects in the thalamus with decreased [(123)I]beta-CIT binding,
      suggesting serotonergic axonal damage; decreased fractional anisotropy,
      suggesting axonal loss; and increased cerebral blood volume probably caused by
      serotonin depletion. Ecstasy had no effect on brain metabolites and apparent
      diffusion coefficients. CONCLUSIONS: Converging evidence was found for a specific
      toxic effect of ecstasy on serotonergic axons in the thalamus.

PMID- 18827289
TI  - Extrapyramidal side-effects of antipsychotics in a randomised trial.
AB  - BACKGROUND: There are claims that second-generation antipsychotics produce fewer
      extrapyramidal side-effects (EPS) compared with first-generation drugs. AIMS: To
      compare the incidence of treatment-emergent EPS between second-generation
      antipsychotics and perphenazine in people with schizophrenia. METHOD: Incidence
      analyses integrated data from standardised rating scales and documented use of
      concomitant medication or treatment discontinuation for EPS events. Mixed model
      analyses of change in rating scales from baseline were also conducted. RESULTS:
      There were no significant differences in incidence or change in rating scales for
      parkinsonism, dystonia, akathisia or tardive dyskinesia when comparing second
      generation antipsychotics with perphenazine or comparing between second
      generation antipsychotics. Secondary analyses revealed greater rates of
      concomitant antiparkinsonism medication among individuals on risperidone and
      lower rates among individuals on quetiapine, and lower rates of discontinuation
      because of parkinsonism among people on quetiapine and ziprasidone. There was a
      trend for a greater likelihood of concomitant medication for akathisia among
      individuals on risperidone and perphenazine. CONCLUSIONS: The incidence of
      treatment-emergent EPS and change in EPS ratings indicated that there are no
      significant differences between second-generation antipsychotics and perphenazine
      or between second-generation antipsychotics in people with schizophrenia.

PMID- 18827291
TI  - Cognitive markers of short-term clinical outcome in first-episode psychosis.
AB  - BACKGROUND: Outcome from psychotic disorders is heterogeneous with poorer
      outcomes frequently identified too late to be influenced. Symptomatic ratings at
      1 or more years following initiation of treatment have been related to cognition
      in first-episode psychosis. However, the relationship between cognition and early
      outcome remains unclear. AIMS: To determine whether specific cognitive domains
      could identify poor short-term outcome among individuals with first-episode
      psychosis. METHOD: One hundred and fifty-one individuals with first-episode
      psychosis were divided into two groups based on 6-month clinical data after the
      initiation of treatment. Six cognitive domains were compared among 78
      participants with poor outcomes, 73 with good outcomes and 31 healthy controls.
      RESULTS: Lower performance on verbal memory (z-scores: poor outcome=-1.3
      (s.d.=1.1); good outcome=-0.8 (s.d.=0.9); P=0.001) and working memory (poor
      outcome=-1.0 (s.d.=1.2); good outcome=-0.4 (s.d.=0.9); P=0.003) identified
      individuals with first-episode psychosis with a poor outcome after 6 months of
      treatment. CONCLUSIONS: The early identification of those individuals with first
      episode psychosis with a poor clinical outcome may encourage clinicians to pay
      special attention to them in the form of alternative pharmacological and
      psychological treatments for a more favourable outcome in the long term.

PMID- 18827292
TI  - Correlation and familial aggregation of dimensions of psychosis in affected
      sibling pairs from China.
AB  - BACKGROUND: A number of studies with conflicting results have examined the
      familiality of schizophrenia syndromes in Western populations. AIMS: The
      objective of this study was to determine, using clinical data from concordant
      sibling pairs, whether symptom dimensions and other clinical characteristics of
      schizophrenia show familial aggregation and are therefore potentially useful
      traits in genetic studies. METHOD: We measured clinical and demographic features,
      and symptom dimensions of schizophrenia in 137 families from China who had two or
      more affected members with schizophrenia. Within-sibling pair correlation was
      assessed with intraclass correlation coefficient and kappa statistics. RESULTS:
      Global functioning, positive, disorganisation and dysphoric symptoms, premorbid
      schizotypal and schizoid traits, premorbid social adjustment, type and age at
      illness onset all showed significant evidence of familial aggregation. DSM-IV
      schizophrenia subtypes were also found to be familial. CONCLUSIONS: This is the
      first study in a large non-European population to confirm that schizophrenia
      dimensions and clinical characteristics show significant familiality, implying
      possible heritability. This supports their use in the delineation of homogeneous
      subsets for future genetic studies.

PMID- 18827293
TI  - Schizophrenia and offspring's risk for adverse pregnancy outcomes and infant
      death.
AB  - BACKGROUND: Women with schizophrenia are at increased risk for adverse pregnancy
      outcomes. It is not known whether offspring born to fathers with schizophrenia
      also have an increased risk. AIMS: To evaluate paternal and maternal influences
      on the association between schizophrenia and pregnancy outcomes. METHOD: A record
      linkage including 2 million births was made using Swedish population-based
      registers. The risk for adverse pregnancy outcomes was evaluated through logistic
      regression. RESULTS: Offspring with a mother or father with schizophrenia faced a
      doubled risk of infant mortality, which could not be explained by maternal
      behaviour alone during pregnancy. Excess infant death risk was largely
      attributable to post-neonatal death. Maternal factors (e.g. smoking) explained
      most of the other risks of adverse pregnancy outcomes among both mothers and
      fathers with schizophrenia. CONCLUSIONS: The risks to offspring whose fathers had
      schizophrenia suggest that, in addition to maternal risk behaviour, non-optimal
      social and/or parenting circumstances are of importance.

PMID- 18827294
TI  - Paternal age at birth and high-functioning autistic-spectrum disorder in
      offspring.
AB  - BACKGROUND: Previous studies have reported the association between advanced
      paternal age at birth and the risk of autistic-spectrum disorder in offspring,
      including offspring with intellectual disability. AIMS: To test whether an
      association between advanced paternal age at birth is found in offspring with
      high-functioning autistic-spectrum disorder (i.e. offspring without intellectual
      disability). METHOD: A case-control study was conducted in Japan. The
      participants consisted of individuals with full-scale IQ>or=70, with a DSM-IV
      autistic disorder or related diagnosis. Unrelated healthy volunteers were
      recruited as controls. Parental ages were divided into tertiles (i.e. three age
      classes). Odds ratios and 95% confidence intervals were estimated using logistic
      regression analyses, with an adjustment for age, gender and birth order. RESULTS:
      Eighty-four individuals with autistic-spectrum disorder but without intellectual
      disability and 208 healthy controls were enrolled. Increased paternal, but not
      maternal, age was associated with an elevated risk of high-functioning autistic
      spectrum disorder. A one-level advance in paternal age class corresponded to a
      1.8-fold increase in risk, after adjustment for covariates. CONCLUSIONS: Advanced
      paternal age is associated with an increased risk for high-functioning autistic
      spectrum disorder.

PMID- 18827296
TI  - Tobacco smoking as a risk factor for major depressive disorder: population-based
      study.
AB  - BACKGROUND: Smoking is disproportionately prevalent among people with psychiatric
      illness. AIMS: To investigate smoking as a risk factor for major depressive
      disorder. METHOD: A population-based sample of women was studied using case
      control and retrospective cohort study designs. Exposure to smoking was self
      reported, and major depressive disorder diagnosed using the Structured Clinical
      Interview for DSM-IV-TR (SCID-I/NP). RESULTS: Among 165 people with major
      depressive disorder and 806 controls, smoking was associated with increased odds
      for major depressive disorder (age-adjusted odds ratio (OR)=1.46, 95% CI 1.03
      2.07). Compared with non-smokers, odds for major depressive disorder more than
      doubled for heavy smokers (>20 cigarettes/day). Among 671 women with no history
      of major depressive disorder at baseline, 13 of 87 smokers and 38 of 584 non
      smokers developed de novo major depressive disorder during a decade of follow-up.
      Smoking increased major depressive disorder risk by 93% (hazard ratio (HR)=1.93,
      95% CI 1.02-3.69); this was not explained by physical activity or alcohol
      consumption. CONCLUSIONS: Evidence from cross-sectional and longitudinal data
      suggests that smoking increases the risk of major depressive disorder in women.

PMID- 18827297
TI  - Psychiatric outcomes 10 years after treatment with antidepressants or
      anxiolytics.
AB  - BACKGROUND: Antidepressants and anxiolytics have demonstrated short-term
      efficacy; however, little is known about the long-term effectiveness of these
      drugs. AIMS: To investigate long-term psychiatric outcomes following
      antidepressant and/or anxiolytic use during an episode of mental disorder in mid
      life. METHOD: Members of the 1946 British birth cohort were assessed for symptoms
      of depression and anxiety at age 43. Among 157 with mental disorder, those using
      antidepressants and/or anxiolytics were compared with those not using medications
      on psychiatric outcomes at age 53. RESULTS: Use of antidepressants or anxiolytics
      was associated with a lower prevalence of mental disorder at age 53 (odds ratio
      (OR)=0.3, 95% CI 0.1-1.0) after adjustment for eight variables in a propensity
      for-treatment analysis. Only 24% of those being treated with medications at age
      43 were still using them at 53. CONCLUSIONS: Use of antidepressants or
      anxiolytics during an episode of mental disorder may have long-term beneficial
      effects on mental health. This may be because of a demonstrated willingness to
      seek help rather than long-term maintenance therapy.

PMID- 18827299
TI  - Cognitive-behavioural therapy for health anxiety in a genitourinary medicine
      clinic: randomised controlled trial.
AB  - BACKGROUND: Little is known about the management of health anxiety and
      hypochondriasis in secondary care settings. AIMS: To determine whether cognitive
      behavioural therapy (CBT) along with a supplementary manual was effective in
      reducing symptoms and health consultations in patients with high health anxiety
      in a genitourinary medicine clinic. METHOD: Patients with high health anxiety
      were randomly assigned to brief CBT and compared with a control group. RESULTS:
      Greater improvement was seen in Health Anxiety Inventory (HAI) scores (primary
      outcome) in patients treated with CBT (n=23) than in the control group (n=26)
      (P=0.001). Similar but less marked differences were found for secondary outcomes
      of generalised anxiety, depression and social function, and there were fewer
      health service consultations. The CBT intervention resulted in improvements in
      outcomes alongside higher costs, with an incremental cost of pound 33 per unit
      reduction in HAI score. CONCLUSIONS: Cognitive-behavioural therapy for health
      anxiety within a genitourinary medicine clinic is effective and suggests wider
      use of this intervention in medical settings.

PMID- 18827301
TI  - Serum levels of P-selectin in men with high-functioning autism.
AB  - Immune dysfunction has been proposed as a mechanism for the pathophysiology of
      autistic-spectrum disorders. The selectin family of adhesion molecules plays a
      prominent role in immune/inflammatory responses. We determined the serum levels
      of three types of soluble-form selectin (sP, sL and sE) in 15 men with high
      functioning autism and 22 age-matched healthy controls by enzyme-linked
      immunosorbent assay. Levels of sP-selectin and sL-selectin were significantly
      lower in patients than in controls. Furthermore, sP-selectin levels were
      negatively correlated with impaired social development during early childhood.

PMID- 18827302
TI  - Guided self-instructions for people with chronic fatigue syndrome: randomised
      controlled trial.
AB  - A minimal intervention, based on cognitive-behavioural therapy for chronic
      fatigue syndrome and consisting of self-instructions combined with email contact,
      was tested in a randomised controlled trial (ISRCTN27293439). A total of 171
      patients participated in the trial: 85 were allocated to the intervention
      condition and 86 to the waiting-list condition. All patients met the Centers for
      Disease Control and Prevention criteria for chronic fatigue syndrome. An
      intention-to-treat analysis showed a significant decrease in fatigue and
      disability after self-instruction. The level of disability was negatively
      correlated with treatment outcome. Guided self-instructions are an effective
      treatment for patients with relatively less severe chronic fatigue syndrome.

PMID- 18827303
TI  - Dedicated community-based services for adults with personality disorder: Delphi
      study.
AB  - Dedicated community-based services have been recommended for people with
      personality disorder, but little is known about how such services should be
      configured. We conducted a Delphi survey to assess opinions about this. A panel
      of expert authors, service providers and service users agreed on only 21 (39%) of
      54 statements on the organisation and delivery of care. Consensus was not reached
      on important issues such as working with people with a history of violent
      offending, the role of community outreach and the use of compulsory treatment.
      Further work needs to be undertaken before the optimal organisation of dedicated
      personality disorder services can be agreed.

PMID- 18827304
TI  - Risk of harm after psychological intervention.

PMID- 18827306
TI  - One-carbon metabolism and depression.

PMID- 18827308
TI  - Risk of harm after psychological intervention.

PMID- 18827310
TI  - Constant pressure fluid infusion into rat neocortex from implantable microfluidic
      devices.
AB  - Implantable electrode arrays capable of recording and stimulating neural activity
      with high spatial and temporal resolution will provide a foundation for future
      brain computer interface technology. Currently, their clinical impact has been
      curtailed by a general lack of functional stability, which can be attributed to
      the acute and chronic reactive tissue responses to devices implanted in the
      brain. Control of the tissue environment surrounding implanted devices through
      local drug delivery could significantly alter both the acute and chronic reactive
      responses, and thus enhance device stability. Here, we characterize pressure
      mediated release of test compounds into rat cortex using an implantable
      microfluidic platform. A fixed volume of fluorescent cell marker cocktail was
      delivered using constant pressure infusion at reservoir backpressures of 0, 5 and
      10 psi. Affected tissue volumes were imaged and analyzed using epifluorescence
      and confocal microscropies and quantitative image analysis techniques. The
      addressable tissue volume for the 5 and 10 psi infusions, defined by fluorescent
      staining with Hoescht 33342 dye, was significantly larger than the tissue volume
      addressed by simple diffusion (0 psi) and the tissue volume exhibiting insertion
      related cell damage (stained by propidium iodide). The results demonstrate the
      potential for using constant pressure infusion to address relevant tissue volumes
      with appropriate pharmacologies to alleviate reactive biological responses around
      inserted neuroprosthetic devices.

PMID- 18827311
TI  - Developing a tissue-engineered neural-electrical relay using encapsulated
      neuronal constructs on conducting polymer fibers.
AB  - Neural-electrical interface platforms are being developed to extracellularly
      monitor neuronal population activity. Polyaniline-based electrically conducting
      polymer fibers are attractive substrates for sustained functional interfaces with
      neurons due to their flexibility, tailored geometry and controlled electro
      conductive properties. In this study, we addressed the neurobiological
      considerations of utilizing small diameter (<400 microm) fibers consisting of a
      blend of electrically conductive polyaniline and polypropylene (PA-PP) as the
      backbone of encapsulated tissue-engineered neural-electrical relays. We devised
      new approaches to promote survival, adhesion and neurite outgrowth of primary
      dorsal root ganglion neurons on PA-PP fibers. We attained a greater than ten-fold
      increase in the density of viable neurons on fiber surfaces to approximately 700
      neurons mm(-2) by manipulating surrounding surface charges to bias settling
      neuronal suspensions toward fibers coated with cell-adhesive ligands. This stark
      increase in neuronal density resulted in robust neuritic extension and network
      formation directly along the fibers. Additionally, we encapsulated these neuronal
      networks on PA-PP fibers using agarose to form a protective barrier while
      potentially facilitating network stability. Following encapsulation, the neuronal
      networks maintained integrity, high viability (>85%) and intimate adhesion to PA
      PP fibers. These efforts accomplished key prerequisites for the establishment of
      functional electrical interfaces with neuronal populations using small diameter
      PA-PP fibers-specifically, improved neurocompatibility, high-density neuronal
      adhesion and neuritic network development directly on fiber surfaces.

PMID- 18827312
TI  - The statistics of a practical seizure warning system.
AB  - Statistical methods for evaluating seizure prediction algorithms are
      controversial and a primary barrier to realizing clinical applications. Experts
      agree that these algorithms must, at a minimum, perform better than chance, but
      the proper method for comparing to chance is in debate. We derive a statistical
      framework for this comparison, the expected performance of a chance predictor
      according to a predefined scoring rule, which is in turn used as the control in a
      hypothesis test. We verify the expected performance of chance prediction using
      Monte Carlo simulations that generate random, simulated seizure warnings of
      variable duration. We propose a new test metric, the difference between algorithm
      and chance sensitivities given a constraint on proportion of time spent in
      warning, and use a simple spectral power-based measure to demonstrate the utility
      of the metric in four patients undergoing intracranial EEG monitoring during
      evaluation for epilepsy surgery. The methods are broadly applicable to other
      scoring rules. We present them as an advance in the statistical evaluation of a
      practical seizure advisory system.

PMID- 18827313
TI  - FPGA design and implementation for EIT data acquisition.
AB  - OXBACT-5 was designed to meet the challenges involved in working in the intensive
      care hospital environment focussed particularly on thoracic imaging of patients
      with respiratory distress and chronic heart failure (CHF). The FPGA-based
      wireless LAN linked multi-channel EIT data acquisition system (DAS) providing 16
      programmable excitation current channels and 64 voltage measurement channels is
      presented. It contains function modules of a PCI bus interface, direct digital
      synthesizers, dual-port memory blocks, digital demodulation and all the command
      and control logic in the FPGA. The whole EIT data acquisition system is fully
      programmable and reconfigurable from the host PC. The excitation frequency,
      excitation patterns, the measuring sequence and the gain of each measurement
      channel can be set from the host PC before each measurement. The demodulation is
      implemented in the FPGA chip to reduce the data rate between the DAS and the host
      PC. In addition, measurement process management is achieved in this FPGA chip.
      Complemented by analogue devices such as ADCs, DACs, analogue buffers and
      analogue multiplexers, the new FPGA-based EIT DAS system is implemented in a very
      compact way for bedside use in intensive care units of hospitals. It is intended
      for applications such as continuous respiration monitoring with data collection
      at 25 frames per second. Image reconstruction times depend on the choice of 2D or
      3D imaging algorithms and the available processing power.

PMID- 18827314
TI  - Improvement in EIS diagnosis accuracy using a multi-frequency parameter analysis
      method: preliminary results.
AB  - In this work we assessed the validity of the multi-frequency parameter (MFP)
      analysis method in distinguishing EIS false positive results. We chose 15
      subjects with invasive duct carcinoma as the control group in which EIS results
      were all positive. In the experiment, three test groups-the Contact, the Skin and
      the Horm groups-were set to correspond to three common types of EIS false
      results. In the Contact group, false positive results were induced by poor
      contact of the measuring probe. In the Skin group, false positive results were
      induced by skin ridges. In the Horm group, false positive results were induced by
      a high hormone level. Based on the MFP analysis method, we obtained the Cole-Cole
      parameters of each subject in the control group and the test groups. Statistical
      analyses showed there was a significant difference in G(0N), G(infinity)N) or
      alpha(N) between the control group and the Contact or the Skin group. A
      significant difference between the control group and the Horm group existed only
      in alpha(N). These results suggested that by means of the MFP analysis method it
      was possible to distinguish between a false positive result and a positive result
      caused by breast cancer. In conclusion, the MFP analysis method appears to be a
      feasible means to improve the diagnosis accuracy of EIS for breast cancer
      detection.

PMID- 18827315
TI  - Quantitative fluorescence imaging of point-like sources in small animals.
AB  - A planar imaging approach is described for the in vivo quantitative
      reconstruction of fluorescent point sources in small animals. The method uses the
      diffusion approximation as a forward model of light propagation from a point
      source in a homogeneous tissue to find source depth and strength. The tissue
      optical properties obtained from video reflectometry measurements were used to
      compensate for the effects of tissue heterogeneity. The method was evaluated on
      images of fluorescent sources implanted 2-8.5 mm deep in the thigh and abdomen of
      rats post mortem. In more than 70% of the total number of implants the source
      depth was retrieved with an error of less than 1 mm. The largest absolute error
      was 1.9 mm. In retrieving source strength, the errors ranged from 0.4% to 89%
      generally increasing with increased source depth.

PMID- 18827316
TI  - Intercomparison of whole-body averaged SAR in European and Japanese voxel
      phantoms.
AB  - This paper provides an intercomparison of the HPA male and female models, NORMAN
      and NAOMI with the National Institute of Information and Communications
      Technology (NICT) male and female models, TARO and HANAKO. The calculations of
      the whole-body SAR in these four phantoms were performed at the HPA, at NICT and
      at the Nagoya Institute of Technology (NIT). These were for a plane wave with a
      vertically aligned electric field incident upon the front of the body from 30 MHz
      to 3 GHz for isolated conditions. As well as investigating the general
      differences through this frequency range, particular emphasis was placed on the
      assumptions of how dielectric properties are assigned to tissues (particularly
      skin and fat) and the consequence of using different algorithms for calculating
      SAR at the higher frequencies.

PMID- 18827317
TI  - Adaptation of a 3D prostate cancer atlas for transrectal ultrasound guided target
      specific biopsy.
AB  - Due to lack of imaging modalities to identify prostate cancer in vivo, current
      TRUS guided prostate biopsies are taken randomly. Consequently, many important
      cancers are missed during initial biopsies. The purpose of this study was to
      determine the potential clinical utility of a high-speed registration algorithm
      for a 3D prostate cancer atlas. This 3D prostate cancer atlas provides voxel
      level likelihood of cancer and optimized biopsy locations on a template space
      (Zhan et al 2007). The atlas was constructed from 158 expert annotated, 3D
      reconstructed radical prostatectomy specimens outlined for cancers (Shen et al
      2004). For successful clinical implementation, the prostate atlas needs to be
      registered to each patient's TRUS image with high registration accuracy in a time
      efficient manner. This is implemented in a two-step procedure, the segmentation
      of the prostate gland from a patient's TRUS image followed by the registration of
      the prostate atlas. We have developed a fast registration algorithm suitable for
      clinical applications of this prostate cancer atlas. The registration algorithm
      was implemented on a graphical processing unit (GPU) to meet the critical
      processing speed requirements for atlas guided biopsy. A color overlay of the
      atlas superposed on the TRUS image was presented to help pick statistically
      likely regions known to harbor cancer. We validated our fast registration
      algorithm using computer simulations of two optimized 7- and 12-core biopsy
      protocols to maximize the overall detection rate. Using a GPU, patient's TRUS
      image segmentation and atlas registration took less than 12 s. The prostate
      cancer atlas guided 7- and 12-core biopsy protocols had cancer detection rates of
      84.81% and 89.87% respectively when validated on the same set of data. Whereas
      the sextant biopsy approach without the utility of 3D cancer atlas detected only
      70.5% of the cancers using the same histology data. We estimate 10-20% increase
      in prostate cancer detection rates when TRUS guided biopsies are assisted by the
      3D prostate cancer atlas compared to the current standard of care. The fast
      registration algorithm we have developed can easily be adapted for clinical
      applications for the improved diagnosis of prostate cancer.

PMID- 18827318
TI  - Benchmarking of a motion sensing system for medical imaging and radiotherapy.
AB  - We have tested the performance of an Optotrak Certus system, which optically
      tracks multiple markers, in both position and time. To do this, we have developed
      custom code which enables a range of testing protocols, and make this code
      available to the community. We find that the Certus' positional accuracy is very
      high, around 20 microm at a distance of 2.8 m. In contrast, we find that its
      timing accuracy is typically no better than around 5-10% for typical data rates,
      whether one is using an ethernet connection or a dedicated SCSI link from the
      system to a host computer. However, with our code we are able to attach very
      accurate timestamps to the data frames, and in cases where regularly-spaced data
      are not an absolute requirement, this will be more than adequate.

PMID- 18827319
TI  - Verification of dynamic radiotherapy: the potential for 3D dosimetry under
      respiratory-like motion using polymer gel.
AB  - Following the implementation of advanced treatment procedures in radiotherapy,
      there is a need for dynamic dose verification in 3D. Gel dosimetry could
      potentially be used for such measurements. However, recently published data show
      that certain types of gels have a dose rate and fractionation dependence. The aim
      of this study was to investigate the feasibility of using a polymer gel dosimeter
      for dose verification of dynamic radiotherapy. To investigate the influence of
      dose rate dependence during respiratory-like motion in and out of the beam, a
      respiration robot together with two types of gel systems (normoxic methacrylic
      acid gel (nMAG) and normoxic polyacrylamide gel (nPAG)) were used. Reference
      measurements were obtained using a linear diode array (LDA). Expected results, if
      there was no influence of the dose rate variation, were calculated by convolving
      the static irradiated gel data with the motion function controlling the robot. To
      investigate the fractionation dependence, the gels were irradiated using gated
      and ungated deliveries. Magnetic resonance imaging was used to evaluate the
      absorbed dose response of the gel. The measured gel data coincided well with the
      LDA data. Also, the calculated data agreed well with the measured dynamic gel
      data, i.e. no dose rate dependence due to motion was observed. The difference in
      the R2 response for the gels receiving ungated and gated, i.e. fractionated,
      deliveries was less than 1% for the nPAG and 4% for the nMAG, for absorbed doses
      up to 2 Gy. The maximum difference was 1.2% for the nPAG and 9% for the nMAG,
      which occurred at the highest given dose (4 Gy). The investigated gels were found
      to be feasible detectors for dose measurements under respiratory-like motion. For
      dose verification of dynamic RT involving gated delivery, e.g. breathing-adapted
      radiotherapy, relative absorbed dose evaluation should be used in order to
      minimize the effects of fractionated irradiation.

PMID- 18827320
TI  - Experimental validation of Monte Carlo calculations with a voxelized Rando
      Alderson phantom: a study on influence parameters.
AB  - The development and improvement of techniques for an accurate dose assessment in
      medical physics is an important task. In this study, we focus on the validation
      of Monte Carlo calculations, by comparing organ doses assessed experimentally
      with thermoluminescent detectors in the Rando-Alderson phantom with doses
      calculated for a voxelized model of the same phantom for some typical x-ray
      procedures. A detailed study has been performed to identify the key parameters
      that affect the determination of organ doses. Initially, TLD measurements were up
      to 65% higher than the calculated values. After the corrections made on TLD
      energy dependence, TLD angular dependence, material composition and field size
      and position, most differences between measurements and calculations are within
      15%. For organs far away from the field the difference is about 30%.

PMID- 18827322
TI  - Planning lung radiotherapy using 4D CT data and a motion model.
AB  - This work is a feasibility study to use a four-dimensional computed tomography
      (4D CT) dataset generated by a continuous motion model for treatment planning in
      lung radiotherapy. The model-based 4D CT data were derived from multiple
      breathing cycles. Four patients were included in this retrospective study.
      Treatment plans were optimized at end-exhale for each patient and the effect of
      respiratory motion on the dose delivery investigated. The accuracy of the
      delivered dose as determined by the number of intermediate respiratory phases
      used for the calculation was considered. The time-averaged geometry of the
      anatomy representing the mid-ventilation phase of the breathing cycle was
      generated using the motion model and a treatment plan was optimized for this
      phase for one patient. With respiratory motion included, the mid-ventilation plan
      achieved better target coverage than the plan optimized at end-exhale when
      standard margins were used to expand the clinical target volume (CTV) to planning
      target volume (PTV). Using a margin to account for set-up uncertainty only,
      resulted in poorer target coverage and healthy tissue sparing. For this patient
      cohort, the results suggest that conventional three-dimensional treatment
      planning was sufficient to maintain target coverage despite respiratory motion.
      The motion model has proved a useful tool in 4D treatment planning.

PMID- 18827321
TI  - Accuracy and reproducibility of tumor positioning during prolonged and multi
      modality animal imaging studies.
AB  - Dedicated small-animal imaging devices, e.g. positron emission tomography (PET),
      computed tomography (CT) and magnetic resonance imaging (MRI) scanners, are being
      increasingly used for translational molecular imaging studies. The objective of
      this work was to determine the positional accuracy and precision with which
      tumors in situ can be reliably and reproducibly imaged on dedicated small-animal
      imaging equipment. We designed, fabricated and tested a custom rodent cradle with
      a stereotactic template to facilitate registration among image sets. To quantify
      tumor motion during our small-animal imaging protocols, 'gold standard' multi
      modality point markers were inserted into tumor masses on the hind limbs of rats.
      Three types of imaging examination were then performed with the animals
      continuously anesthetized and immobilized: (i) consecutive microPET and MR images
      of tumor xenografts in which the animals remained in the same scanner for 2 h
      duration, (ii) multi-modality imaging studies in which the animals were
      transported between distant imaging devices and (iii) serial microPET scans in
      which the animals were repositioned in the same scanner for subsequent images.
      Our results showed that the animal tumor moved by less than 0.2-0.3 mm over a
      continuous 2 h microPET or MR imaging session. The process of transporting the
      animal between instruments introduced additional errors of approximately 0.2 mm.
      In serial animal imaging studies, the positioning reproducibility within
      approximately 0.8 mm could be obtained.

PMID- 18827323
TI  - A model of speckle contrast in optical coherence tomography for characterizing
      the scattering coefficient of homogenous tissues.
AB  - We present a theoretical model for analyzing the speckle contrast of optical
      coherence tomography (OCT). This model is based on the addition of noise and an
      OCT signal in the logarithmic scale. The theoretical model reveals that, for the
      superficial layer of homogenous tissue, the contrast ratio is a linear function
      of the location of the coherence gate in the sample and the slope of this linear
      dependence is proportional to the scattering coefficient. The theoretical model
      is consistent with the experimental results, suggesting that the slope can be
      useful to characterize the scattering coefficient of the homogenous samples.

PMID- 18827324
TI  - Vastus lateralis fascicle length changes during stair ascent and descent.
AB  - STUDY DESIGN: Experimental descriptive laboratory study. OBJECTIVES: To describe
      the change in fascicle length of the human vastus lateralis (VL) muscle during
      the stance phase of stair ascent and descent. BACKGROUND: Muscle fascicle length
      changes during lower limb functional activities, such as walking and jumping, do
      not always coincide with joint angle changes. METHODS AND MEASURES: Thirty-three
      healthy, college-age women walked up and down 4 standard steps. VL fascicle
      length and pennation angle were measured using real-time ultrasonography. Knee
      angle was monitored using an electrical goniometer. Foot switches indicated foot
      contact and release. VL muscle activity was monitored using surface electrodes.
      The VL muscle-tendon complex and tendon length were calculated based on published
      models. RESULTS: During initial weight acceptance in stair ascent, the knee joint
      extended only 3 degrees , VL muscle activity increased to a maximum, VL fascicles
      shortened, and the tendon lengthened. As the knee extended to ascend the step,
      the fascicles and tendon shortened throughout the movement. During weight
      acceptance in stair descent, VL muscle activity increased, VL fascicle length did
      not change significantly, but the tendon lengthened as 10 degrees of knee flexion
      occurred. As the knee flexed to complete descent, VL muscle activity peaked, and
      VL fascicles and tendon lengthened. CONCLUSION: VL fascicles shorten and lengthen
      as expected during the respective knee extension and knee flexion phases of stair
      ascent and descent. However, during initial weight acceptance in both stair
      ascent and descent, the fascicle length change did not coincide with the knee
      joint kinematics.

PMID- 18827325
TI  - The time course of musculotendinous stiffness responses following different
      durations of passive stretching.
AB  - STUDY DESIGN: Repeated-measures experimental design. OBJECTIVE: To examine the
      acute effects of different durations of passive stretching on the time course of
      musculotendinous stiffness (MTS) responses in the plantar flexor muscles.
      BACKGROUND: Stretching is often implemented prior to exercise or athletic
      competition, with the intent to reduce the risk of injury via decreases in MTS.
      METHODS AND MEASURES: Twelve subjects (mean +/- SD age, 24 +/- 3 years; stature,
      169 +/- 12 cm; mass, 71 +/- 17 kg) participated in 4 randomly-ordered
      experimental trials: control with no stretching, 2 minutes (2min), 4 minutes
      (4min), and 8 minutes (8min) of passive stretching. The passive-stretching trials
      involved progressive repetitions of 30-second passive stretches, while the
      control trial involved 15 minutes of resting. MTS assessments were conducted
      before (prestretching), immediately after (poststretching), and at 10, 20, and 30
      minutes poststretching on a Biodex System 3 isokinetic dynamometer. RESULTS: MTS
      decreased (P<.05) immediately after all stretching conditions (2min, 4min, and
      8min). However, MTS for the 2min condition returned to baseline within 10
      minutes, whereas MTS after the 4min and 8min passive-stretching conditions
      returned to baseline within 20 minutes. CONCLUSIONS: Practical durations of
      passive stretching resulted in significant decreases in MTS; however, these
      changes return to baseline levels within 10 to 20 minutes.

PMID- 18827326
TI  - Intrarater reliability of CROM measurement of cervical spine active range of
      motion in persons with and without neck pain.
AB  - STUDY DESIGN: Clinical measurement, intrarater reliability study. OBJECTIVES: To
      determine the intrarater reliability of cervical active range of motion (AROM)
      measurement of subjects with and without neck pain using the cervical range-of
      motion device (CROM). BACKGROUND: Cervical spine AROM data are used by physical
      therapists to assist in identifying movement impairment, monitor patient
      progress, and evaluate the effectiveness of intervention. Presently, insufficient
      literature exists regarding the intrarater reliability of cervical AROM
      measurements using the CROM. METHODS AND MEASURES: Twenty-five adult subjects
      without neck pain and 22 adult subjects with neck pain volunteered for the study.
      Two trials of cervical AROM measurement (6 movements) were performed for each
      subject. Practice sessions, methods of measurement, and rest time between trials
      were standardized; order of measurement was randomized. RESULTS: The intraclass
      correlation coefficients (ICC3,1) for the subjects without neck pain ranged from
      0.87 for flexion (95% confidence interval [CI]: 0.76-0.95) to 0.94 for left
      rotation (95% CI: 0.87-0.97). The standard error of the measurement ranged from
      2.3 degrees to 4.0 degrees . The ICCs for the subjects with neck pain ranged from
      0.88 for flexion (95% CI: 0.73-0.95) to 0.96 for left rotation (95% CI: 0.91
      0.98). The standard error of the measurement ranged from 2.5 degrees to 4.1
      degrees . Minimal detectable change ranged from 5.4 degrees for left rotation in
      the subjects without neck pain to 9.6 degrees for flexion in the subjects with
      neck pain. CONCLUSION: Intrarater reliability for cervical AROM measurement of
      persons with and without neck pain is sufficient to consider use of the CROM in
      clinical practice, although changes between 5 degrees to 10 degrees are needed to
      feel confident that a real change in spine mobility has occurred.

PMID- 18827327
TI  - Utility of the frontal plane projection angle in females with patellofemoral
      pain.
AB  - STUDY DESIGN: Case-control study of females with patellofemoral pain syndrome
      (PFPS) and a control group. OBJECTIVES: Three different approaches were used to
      examine the utility of a 2-dimensional (2-D) frontal plane projection angle
      (FPPA) measure of knee alignment. First, we measured the FPPA association with
      respect to 3-dimensional (3-D) lower extremity joint rotations during single-leg
      squats. Second, we determined the correlation of the FPPA during single-leg
      squats with hip and knee joint rotations during running and single leg jumping.
      Third, we compared the FPPA between females with and without PFPS. BACKGROUND:
      PFPS is associated with altered lower extremity kinematics during weight-bearing
      activities that decrease retropatellar contact area and increase retropatellar
      stress. An objective and simple procedure to quantify altered kinematics during
      weight-bearing activities may help clinicians identify individuals who may likely
      benefit from interventions to improve lower extremity kinematics. METHODS AND
      MEASURES: Twenty females with PFPS and 20 healthy female controls performed
      single-leg squats, running, and repetitive single-leg jumps while 3-D lower
      extremity kinematics were recorded. The FPPA was recorded by a digital camera
      during single-leg stance and single-leg squats. Correlation coefficients were
      used to quantify the association between the FPPA and transverse and frontal
      plane hip and knee angles for all activities. Independent t tests were used to
      compare FPPA values between groups. RESULTS: FPPA values representing medial
      displacement of the knee during single-leg squats were associated with increased
      hip adduction (r = 0.32 to 0.38, P<.044) and knee external rotation (r = 0.48 to
      0.55, P<.001) across activities. FPPA values for the PFPS group reveal greater
      medial displacement of the knee compared with those of the control group during
      single-leg squats (P = .012). CONCLUSION: The association between the FPPA and
      lower extremity kinematics that are associated with PFPS suggest that the FPPA
      during single-leg squats may be a useful clinical measure. However, these methods
      should not be used to quantify 3-D joint rotations.

PMID- 18827328
TI  - Isolated knee pain: a case report highlighting regional interdependence.
AB  - STUDY DESIGN: Case report. BACKGROUND: A number of pain referral patterns for
      sacroiliac dysfunction have been reported in the literature. However, very little
      has been written about pain localized to the knee joint for cases involving
      sacroiliac dysfunction. CASE DESCRIPTION: A 25-year-old female runner was self
      referred to physical therapy for medial knee pain of 4(1/2) weeks' duration
      without a significant onset event. The pain completely curtailed her training for
      the Boston Marathon. Examination of the patient's knee and hip did not reveal any
      abnormal findings and there was no reproduction of pain with any test procedures
      except for medial knee joint tenderness to palpation. Additional, more proximal
      examination suggested significant asymmetry of sacral bony landmarks of the
      pelvic girdle without significant findings on the provocation tests of the
      sacroiliac joint. A single session of manual therapy procedures directed to the
      pubic symphysis and sacroiliac joint ipsilateral to the side of knee pain was
      provided. OUTCOMES: The patient was able to return to running without further
      incident of knee pain after a single therapy session. DISCUSSION: This case
      suggests the importance of regional interdependence in the examination of
      patients with an apparently common clinical problem. Furthermore, the case
      describes a previously unreported presentation of local knee pain possibly
      attributable to sacroiliac joint dysfunction.

PMID- 18827329
TI  - Changes in deep abdominal muscle thickness during common trunk-strengthening
      exercises using ultrasound imaging.
AB  - STUDY DESIGN: Cross-sectional study design. OBJECTIVES: To characterize changes
      in muscle thickness in the transversus abdominis (TrA) and internal oblique (IO)
      muscles during common trunk-strengthening exercises, and to determine whether
      these changes differ based on age. BACKGROUND: Although trunk-strengthening
      exercises have been found to be useful in treating those with low back pain
      (LBP), our understanding of the relative responses of the TrA and IO muscles
      during different exercises is limited. METHODS AND MEASURES: Six commonly
      prescribed trunk-strengthening exercises were performed by 120 subjects (40
      subjects per age group: 18-30, 31-40, and 41-50 years). Ultrasound imaging was
      used to measure the thickness of the TrA and IO during the resting and contracted
      state of each exercise. The average thickness of the muscles while in the
      contracted position was divided by the thickness values in the resting position
      for each exercise, based on 2 performances of each exercise. Two 3-by-6 repeated
      measures analyses of variance were used to determine significant changes in
      muscle thickness of the TrA and IO, based on age group and exercise performed.
      RESULTS: For both muscles, the trunk exercise-by-age interaction effect (TrA, P =
      .358; IO, P = .217) and the main effect for age (TrA, P = .615; IO, P = .219)
      were not significant. A significant main effect for trunk exercise for both
      muscles (P<.001) was found. The horizontal side-support (mean +/- SD contracted
      rest thickness ratio: TrA, 1.95 +/- 0.69; IO, 1.88 +/- 0.52) and the abdominal
      crunch (mean +/- SD contracted-rest thickness ratio: TrA, 1.74 +/- 0.48; IO, 1.63
      +/- 0.41) exercises resulted in the greatest change in muscle thickness for both
      muscles. The abdominal drawing-in maneuver (mean +/- SD contracted-rest thickness
      ratio: TrA, 1.73 +/- 0.36; IO, 1.14 +/- 0.33) and quadruped opposite upper and
      lower extremity lift (mean +/- SD contracted-rest thickness ratio: TrA, 1.59 +/-
      0.49; IO, 1.25 +/- 0.36) exercises resulted in changes in TrA muscle thickness
      with minimal changes in IO muscle thickness. CONCLUSION: Changes in TrA and IO
      muscle thickness differed across 6 commonly prescribed trunk-strengthening
      exercises among healthy subjects without LBP. These differences did not vary by
      age. This information may be useful for informing exercise prescription.

PMID- 18827330
TI  - A founding father of manual therapy has passed away.

PMID- 18827331
TI  - How should we interpret measures of patients' fear of movement, injury, or
      reinjury in physical therapist practice?

PMID- 18827332
TI  - Chiari malformation in a patient presenting with knee pain.

PMID- 18827334
TI  - Development and evaluation of a novel gene delivery vehicle composed of
      adenovirus serotype 35.
AB  - The capacity of gene delivery vehicles is considered to be a critical factor
      determining the success of gene therapy. To date, various types of gene delivery
      vehicle have been developed. Among them, recombinant adeno-virus (Ad) vectors
      have potential that has favored their worldwide use in vitro and in vivo.
      Conventional Ad vectors are composed of subgroup C Ad serotype 5 (Ad5), although
      it has been clarified that the drawbacks of Ad5 vectors are a high seroprevalence
      of Ad5 in adults and low transduction efficiencies in cells lacking the primary
      receptor for Ad5, coxsackievirus and adenovirus receptor. To overcome these
      problems, we developed a novel Ad vector fully composed of Ad serotype 35 (Ad35).
      Ad35 vectors show a wide tropism for human cells because Ad35 binds to human
      CD46, which is ubiquitously expressed on almost all human cells, as a primary
      receptor. In addition, anti-Ad5 antibodies do not inhibit Ad35 vector-mediated
      transduction and the seroprevalence of Ad35 in adults is lower than that of Ad5.
      This paper reviews our studies on the development and evaluation of Ad35 vectors.
      Ad vectors derived from other Ad serotypes different from Ad5, including Ad35,
      are expected to be gene delivery vehicles alternative to conventional Ad5
      vectors.

PMID- 18827335
TI  - Physiology and pharmacology of the gut nutrient perception. Foreword.

PMID- 18827336
TI  - Brain activation by umami substances via gustatory and visceral signaling
      pathways, and physiological significance.
AB  - Monosodium L-glutamate (MSG) elicits a unique taste termed umami and is widely
      used as a flavor enhancer in a variety of cuisines. Recent studies suggest the
      existence of L-glutamate (GLU) receptors and its transduction molecules in the
      gut mucosa as well as in the oral cavity. The vagal gastric afferent fibers
      respond specifically to the luminal stimulation of GLU in the stomach. GLU
      administration in the stomach also activates several brain areas (insular cortex,
      basal ganglia, limbic system, and hypothalamus). Ingestion of MSG enhanced
      secretion of digestive juices and insulin. Spontaneous ingestion of an MSG
      solution at the most preferred concentration (1% (w/v)) reduced weight gain, fat
      deposition, and plasma leptin levels without affecting food intake, naso-anal
      length (an index of somatic development), and lean mass in rats. These results
      suggest that umami signaling via gustatory and visceral pathways may play an
      important role in the process of digestion, absorption, metabolism, and other
      physiological functions via activation of the brain.

PMID- 18827337
TI  - Multiple receptor systems for glutamate detection in the taste organ.
AB  - L-Glutamate and 5'-ribonucleotides such as guanosine-5'-monophosphate (GMP) and
      inosine-5'-monophosphate (IMP) elicit a unique taste called 'umami' that is
      distinct from the tastes of sweet, salty, sour, and bitter. For umami, like sweet
      and bitter compounds, taste signaling is initiated by binding of tastants to G
      protein-coupled receptors (GPCR) in taste bud cells. To date, several GPCRs for
      umami compounds have been identified in taste cells, including the heterodimer
      T1R1/T1R3, and truncated type 1 and 4 metabotropic glutamate receptors missing
      most of the N-terminal extracellular domain (taste-mGluR4 and truncated-mGluR1).
      Apparently contradictory data in T1R3 knock-out (KO) mouse models have been
      reported. One study showed that behavioral preference and taste nerve responses
      to umami stimuli in T1R3-KO mice were totally abolished, suggesting that
      T1R1/T1R3 is a sole receptor for umami taste. The other reported reduced but not
      abolished responses to umami in T1R3-KO mice, suggesting existence of multiple
      receptors for umami taste. In this paper, we summarized the data from recent
      studies that further addressed this issue by using different experimental
      techniques. Some of the studies provided additional evidence for the existence of
      umami receptor systems mediated by mGluR1 and mGluR4 in addition to T1R1/T1R3. It
      is proposed that the signal mediated by the pathway involving T1R1/T1R3 may play
      a different role from that derived from the mGluRs. The former occurs mainly in
      the anterior tongue, and plays a major role in preference behavior, whereas the
      latter occurs mainly in the posterior tongue and contributes to behavioral
      discrimination between umami and other taste compounds.

PMID- 18827338
TI  - Immunohistochemical and morphologic basis for glutamate signaling in the rat
      stomach.
AB  - Physiologic studies conducted in rats have demonstrated that afferent fibers of
      the gastric branch of the vagus nerve increase their firing rate with the
      intragastric administration of the amino acid glutamate, and the increased firing
      rate is blocked by the depletion of serotonin (5-HT), administration of the
      blocker for the serotonin type-3 receptor (SR3), or nitric oxide synthase (NOS).
      To understand glutamate signaling in the gastric mucosa at the cellular level, we
      have been studying rats as an animal model using anatomic and immunohistochemical
      procedures. Our results have indicated that 5-HT-immunoreactive (ir) cells are
      present in the superficial part of the gastric mucosal epithelium and in the base
      of the fundic glands, whereas immunoreactivity for SR3 is localized in the neck
      and its vicinity of the fundic glands. Further, NOS1/neuronal NOS-ir cells with a
      bipolar shape are located in the lamina propria where a dense network of neuronal
      cells is present. These results suggest that complex cellular events take place
      during intragastric glutamate signaling.

PMID- 18827339
TI  - Physiological roles of dietary free glutamate in gastrointestinal functions.
AB  - The appropriate recognition of nutrients in gastrointestinal tract has an
      important role in the maintenance of healthy body functions. Perception of
      nutrients in gastrointestinal tract influences not only the regulation of
      gastrointestinal functions such as digestion and absorption, but also the
      subsequent formation of ingestive behaviors and food preferences. Glutamate is
      widely distributed amino acids, approximately 15-45% in the dietary protein as
      the total of free- and bound-forms. To note is that, glutamate is implicated in
      numerous physiological and metabolic functions in the body as a nutrient, in
      addition, free glutamate in the food is also known as the source of umami, one of
      the five basic taste. Taste is basically percepted on the tongue in the oral
      cavity via the specific taste sensors (receptors and/or transporters), however,
      the recent studies suggest the functional roles of taste sensors in the
      regulation of gastrointestinal tract. Interestingly, we recently found the
      presence of specific glutamate-sensing systems in the lumen of the stomach. In
      addition, we have been vigorously studying the physiological roles of dietary
      free glutamate in the body through experimental animals and human. In this topic,
      we review the beneficial roles of dietary free glutamate in the regulation of
      gastrointestinal functions and propose some application of the benefits for the
      clinical gastrointestinal disorders.

PMID- 18827340
TI  - Vesicular glutamate transporter acts as a metabolic regulator.
AB  - Vesicular glutamate transporter (VGLUT) is responsible for the active transport
      of L-glutamate into synaptic vesicles and, thus, plays an essential role in the
      glutamatergic chemical transmission in the central and peripheral nervous
      systems. Recent studies indicated that VGLUT is also expressed and localized in
      various secretory vesicles in non-neuronal peripheral organelles such as hormone
      containing secretory granules in endocrine cells. L-Glutamate is stored in VGLUT
      containing organelles, secreted upon stimulation, and then acts as a paracrine
      and/or autocrine modulator to regulate cellular functions. Thus, VGLUT is a key
      molecule for glutamate signaling and is the core of a novel signaling system.

PMID- 18827341
TI  - Free fatty acid receptors and drug discovery.
AB  - Utilizing the human genome database, the recently developed G-protein-coupled
      receptor (GPCR) deorphanizing strategy successfully identified multiple receptors
      of free fatty acids (FFAs) and is proposed to play a critical role in a variety
      of physiologic homeostasis mechanisms. GPR40 and GPR120 are activated by medium-
      and long-chain FFAs, whereas GPR41 and GPR43 are activated by short-chain FFAs.
      GPR40, which is preferentially expressed in pancreatic beta-cells, mediates
      insulin secretion. On the other hand, GPR120, which is abundantly expressed in
      the intestine, functions as a receptor for unsaturated long-chain FFAs and
      promotes the secretion of glucagon-like peptide-1 (GLP-1). In this review, we
      summarize the identification, structure, and pharmacology of the receptors and
      speculate on the respective physiologic roles that FFA receptor family members
      may play.

PMID- 18827342
TI  - A possible application of monosodium glutamate to nutritional care for elderly
      people.
AB  - Recently, it has been clarified that glutamate (Glu) can stimulate the umami
      taste as well as the visceral sensation to help the gastric protein digestion.
      Our survey suggests the possibility that the amount of free Glu in hospital foods
      is lower than that in ordinary foods. In the present study, monosodium glutamate
      (MSG) was supplemented to meals for 11 elderly inpatients during 2 months, and
      the fortification effects on their nutritional status, general condition, and
      quality of life (QOL) were investigated. The degree of recognition was improved,
      and peripheral lymphocytes were increased, even when there was no change in
      nutritional intake or protein nutritional status. Based on these results, we
      concluded that appropriate utilization of Glu for nutritional care of the elderly
      people would be useful for improving QOL.

PMID- 18827343
TI  - Role of lipid-derived free radical in bleomycin-induced lung injury in mice:
      availability for ESR spin trap method with organic phase extraction.
AB  - Bleomycin is well known as causative molecule for acute lung injury and
      interstitial pneumonia. The free radical production from bleomycin is thought to
      play an important role in the pathogenesis of acute lung injury and interstitial
      pneumonia. However, there was no direct evidence of free radical production in
      this model. Therefore, we examined in vivo radical production by mice treated
      with a bleomycin using electron spin resonance with the spin trap, alpha-(4
      pyridyl-1-oxide)-N-tert-butylnitrone. Six hours after instillation of bleomycin,
      the lung exposed to bleomycin gave a lipid-derived free radical adduct, which
      would support evidence for in vitro lipid peroxidation resulting from bleomycin
      administration. In the treatment of deferoxamine, chelating agent for iron and
      other metals, to reduce the bleomycin induced free radical production, parallel
      to decrease the lipid-derived free radical production by deferoxamine,
      pathophysiological findings of lung injuries were improved by deferoxamine. In
      conclusion, this is a first paper of in vivo direct evidence of production of
      free radical from bleomycin-induced lung injury. It is suggested that this method
      may be used in many kinds of lung disease models, which have potentials of free
      radical production to cause lung damage.

PMID- 18827344
TI  - Development and application of a capillary electrophoretic method for the
      composition analysis of a typical heteropolysaccharide from Codonopsis pilosula
      NANNF.
AB  - A simple capillary electrophoretic method based on 1-phenyl-3-methyl-5-pyrazolon
      (PMP) derivatization has been developed for simultaneous separation and
      determination of nine aldoses (xylose, arabinose, glucose, rhamnose, fucose,
      galactose, mannose, glucuronic acid and galacturonic acid). The separation of PMP
      labeled monosaccharide derivatives was carried out in uncoated capillary (48.5 cm
      x 75 microm i.d.) and under the selected optimum conditions of pH 11.0, 200 mM
      borate buffer at applied voltage 15 kV and capillary temperature 20 degrees C,
      the nine PMP-monosaccharides could be perfectly separated from each other within
      40 min. Furthermore, the developed method was firstly applied to determine the
      sugar composition in the polysaccharide isolated from Chinese Codonopsis
      pilosula. The results showed that C. pilosula polysaccharide was a typically
      acidic heteropolysaccharide and was composed of arabinose, glucose, rhamnose,
      galactose, mannose, glucuronic acid and galacturonic acid in the molar contents
      of 48.1, 103.5, 16.1, 48.5, 7.5, 4.2 and 119.1 microM, respectively. The assay
      results were satisfactory.

PMID- 18827345
TI  - Determination of isepamicin in human plasma by HPLC with fluorescence detection
      after derivatization using 6-aminoquinolyl-N-hydroxysuccinimidyl-carbamate.
AB  - A simple and rapid high-performance liquid chromatographic method has been
      developed for determination in human plasma of isepamicin (ISP), an
      aminoglycoside antibiotic agent. After protein precipitation and clean-up
      procedure to remove lipophilic contaminants, ISP is derivatized pre-column with 6
      aminoquinolyl-N-hydroxysuccinimidyl-carbamate for fluorescence detection.
      Chromatographic separations are achieved using C(18) column and mobile phase
      consisting of 20 mM KH(2)PO(4) containing 8 mM triethylamine (pH 7.0) and
      acetonitrile (78/22, v/v). Amikacin was used as an internal standard. The
      calibration curve was linear over a concentration range of 0.5-50 microg/ml. The
      limit of quantification was 0.5 microg/ml. The intra- and inter-day variabilities
      of ISP were both less than 17.5%. Both derivatives were stable for at least a
      week at ambient condition. This assay procedure should have useful application in
      therapeutic drug monitoring of ISP.

PMID- 18827346
TI  - Optimization of ginsenosides hydrolyzing beta-glucosidase production from
      Aspergillus niger using response surface methodology.
AB  - To optimize ginsenosides hydrolyzing beta-glucosidase production from Aspergillus
      niger, response surface methodology was carried out in two stages. The Plackett
      Burman design was achieved to screen the important variables that influence beta
      glucosidase production. Among 10 variables (wheat bran, soybean powder, CaCl(2),
      ginsenosides, KH(2)PO(4), MgSO(4), polyethylene glycol (PEG), medium volume,
      inoculum size, and stirring speed), it was found that wheat bran, KH(2)PO(4), and
      stirring speed had significant effect on beta-glucosidase activity due to very
      low p-values (p<0.05). Subsequently, wheat bran, KH(2)PO(4), and stirring speed
      were further optimized using central composite design. The optimal beta
      glucosidase production was predicted to be 4650.14 U/ml with the combination of
      factors (wheat bran, 34.51 g/l; KH(2)PO(4), 1.78 g/l; stirring speed, 161.60
      rpm/min). Finally, under optimal fermentation conditions, ginsenoside Rb(1) was
      converted to Rd and F(2) by A. niger within 10 min. Little compound K was
      detected at 30 min, and finally F(2) was completely transformed to compound K
      within 8 h. The putative conversion pathway of Rb(1) by A. niger was Rb(1), Rd,
      F(2), and compound K.

PMID- 18827347
TI  - Pyruvate kinase is protected by glutathione-dependent redox balance in human red
      blood cells exposed to reactive oxygen species.
AB  - To determine the antioxidant role of glutathione (GSH) in human red blood cells
      (RBCs), we investigated the effect of disrupting GSH homeostasis on the oxidative
      modification of thiol-dependent enzymes by exposure to tert-butyl hydroperoxide
      (BHP). When hemolysate was incubated with BHP, significant decreases in enzyme
      activity were observed. However, the inactivation did not occur in intact RBC
      suspensions that were exposed to BHP. In this study, we used two independent
      treatments aimed at decreasing the level of reduced form of GSH, pre-incubation
      with a glutathione reductase inhibitor or glucose-free medium to examine the
      influences of preventing GSH-dependent antioxidant and reactivation activity on
      thiol-dependent enzyme. Pyruvate kinase (PK) activity clearly decreased along
      with depletion of GSH compared to other glycolytic enzyme activities by BHP
      exposure in RBCs. The addition of GSH, but not glucose, before BHP exposure
      completely prevented the inactivation of PK in hemolysate; however, partial
      reactivation of inactivated PK was observed by post-addition of both GSH and
      glutaredoxin at an early stage during BHP exposure. Moreover, hydroxyl radicals
      but not hydrogen peroxide inactivated PK. These results suggest that PK is highly
      susceptible to radicals and that GSH is essential to protect PK activity by not
      only directly scavenging radicals but also by systematically reactivating
      oxidized enzyme in human RBCs.

PMID- 18827348
TI  - Nitric oxide and peroxynitrite regulate transporter transcription in rat liver
      slices.
AB  - To determine the role of nitric oxide (NO) in rat liver transporter regulation,
      we investigated in precision-cut liver slices the effect of NO and peroxynitrite
      (ONOO(-)), a reaction product of NO with superoxide (O(2(-))), on mRNA levels of
      13 influx and efflux transporters. To inactivate Kupffer cells (KCs), liver
      slices were prepared from rats treated with gadolinium chloride (Gd). Transporter
      mRNA levels were determined after incubation of untreated (normal-slices) and Gd
      pretreated slices (Gd-slices) for 18 h with Spermine NONOate (SpNO), an NO donor,
      and SIN-1 (3-(4-morpholinyl) sydnonimine hydrochloride, SIN), a ONOO(-) donor.
      SpNO and SIN varied all transporter mRNA levels examined, except organic anion
      transporting polypeptide 1b2 (Oatp1b2/Oatp4). SpNO in normal-slices and SIN in Gd
      and normal-slices generally decreased influx and increased efflux transporter
      transcription. In contrast, these effects were not observed in Gd-slices treated
      with SpNO. SpNO and SIN in normal-slices commonly decreased organic anion
      transporter 2 (Oat2) and increased multidrug resistance-associated protein 2
      (Mrp2) transcription, but differentially regulated bile salt export pump (Bsep)
      and multidrug resistance protein 2 (Mdr2) transcription, the up-regulation by
      SpNO and the down-regulation by SIN. In addition, the induction of tumor necrosis
      factor (TNF)-alpha and interleukin (IL)-1beta was not observed after incubation
      with SpNO or SIN. These findings suggest that NO and ONOO(-) play a role in the
      regulation of rat transporter transcription in hepatocytes, which communicate
      with KCs, in a proinflammatory cytokine-independent manner.

PMID- 18827349
TI  - Blockade of the aryl hydrocarbon receptor pathway triggered by dioxin, polycyclic
      aromatic hydrocarbons and cigarette smoke by Phellinus linteus.
AB  - Environmental pollutants including halogenated and polycyclic aromatic
      hydrocarbons activate the aryl hydrocarbon receptor (AhR) and thereby cause a
      wide range of pathological changes. Development of AhR antagonists will be useful
      for prevention and treatment of diseases related to AhR activation. Towards this
      end, we aimed in the present study at seeking for potential inhibitors of the AhR
      pathway in mycelial extracts using the dioxin responsive element-based sensing
      via secreted alkaline phosphatase (DRESSA). Through the screening of 13 mycelia,
      extracts prepared from Phellinus linteus, Cordyceps militaris and Hericium
      erinaceum inhibited activation of AhR by 2,3,7,8-tetrachlorodibenzo-p-dioxin,
      benzo[a]pyrene or 3-methylcholanthrene. Subsequent studies revealed that only
      Phellinus linteus suppressed activation of AhR and AhR-dependent gene expression
      triggered by all of these agonists. Cigarette smoke is known to contain a number
      of halogenated and polycyclic aromatic hydrocarbons. We found that Phellinus
      linteus has the potential to block activation of AhR and AhR-dependent gene
      expression triggered by cigarette smoke. Furthermore, the inhibitory effect of
      Phellinus linteus on the AhR pathway was independent of; 1) depression of AhR or
      AhR nuclear translocator, and 2) induction of AhR repressor. We conclude that
      Phellinus linteus contains potent inhibitor(s) of AhR activation and may be
      useful for prevention of pathologies associated with aberrant activation of AhR.

PMID- 18827350
TI  - Abnormal motor function and the expression of striatal dopamine D2 receptors in
      manganese-treated mice.
AB  - Manganese (Mn) plays an important role in the etiology of several neurobehavioral
      disorders, but there is a lack of data regarding its specific effects on
      neurotransduction, especially dopaminergic neurotransduction. We investigated the
      relationship between motor deficits and alterations in the expression of tyrosine
      hydroxylase (TH) and dopamine D2-like receptors (DR), including the three
      dopaminergic subtypes, D2, D3, and D4, in low- and high-dose Mn-treated mice.
      After administration of Mn (intraperitoneal injections of 20 or 40 mg/kg
      MnCl(2).4H(2)O once per day for 5 d), motor activity and expression of TH and DR
      were examined in the striatum of the mouse brain. Mn treatment resulted in
      significant decrease in coordination and/or impaired motor learning after 5 d of
      treatment and this effect remained until 10 d after the end of Mn treatment. The
      expression of dopamine D2-like receptor D2 (DRD2), but not TH, DRD3, or DRD4, in
      the striatum was dose-dependent, and statistically significant increases were
      seen at the mRNA and protein levels. These findings indicate that Mn-induced
      motor deficits may be modulated in part by the expression of DRD2 in the
      striatum. In addition, our results suggest that the disturbance of dopaminergic
      neurotransmission mediated by DRD2 may be involved in the pathogenesis of Mn
      neurotoxicity.

PMID- 18827351
TI  - Antimicrobial effects of drugs against multidrug-resistant Pseudomonas
      aeruginosa.
AB  - We evaluated the effects of antimicrobial drugs on four strains of Pseudomonas
      aeruginosa that are resistant to eight widely used antipseudomonal drugs
      (piperacillin, piperacillin-tazobactam, imipenem, meropenem, ceftazidime,
      aztreonam, amikacin, ciprofloxacin) and colistin. In the killing test, colistin
      (2 microg/ml) was the most effective, followed by aztreonam (48 microg/ml),
      piperacillin-tazobactam (192-4 microg/ml), piperacillin (192 microg/ml), and a
      three drug combination of azetreonam (16 microg/ml), ceftazidime (16 microg/ml),
      and amikacin (4 microg/ml). Six hours after drug addition, colistin (2
      microg/ml), aztreonam (48 microg/ml), piperacillin-tazobactam (192-4 microg/ml),
      piperacillin (192 microg/ml), and the above three drug combination had
      bacteriostatic effects on all four strains. Colistin, three time breakpoint of
      aztreonam, piperacillin, or piperacillin-tazobactam, and the three drug
      combination of aztreonam, ceftazidime, and amikacin were effective in vitro.

PMID- 18827352
TI  - Microbial contamination of fruit and vegetables and their disinfection.
AB  - We evaluated the microbial contamination of 17 types of vegetable and 10 types of
      fruit after 30-s washing with tap water with and without subsequent disinfection
      by 10-min immersion in 0.01% (100 ppm) sodium hypochlorite. The mean microbial
      contamination level of 9 types of leafy vegetable was 2.8 x 10(5) colony-forming
      units (CFU)/g after washing with water and 3.4 x 10(4) CFU/g after washing
      followed by disinfection. The mean microbial contamination level of 8 types of
      nonleafy vegetable was 3.4 x 10(4) CFU/g after washing with water and 1.0 x 10(4)
      CFU/g after washing followed by disinfection. The mean microbial contamination
      level of 10 types of unpeeled fleshy fruit was 9.3 x 10(3) CFU/g after washing
      with water and 1.3 x 10(3) CFU/g after washing followed by disinfection. The
      contaminants in vegetables and unpeeled fruit were similar after washing and
      after washing followed by disinfection, including Pseudomonas fluorescens and
      Pseudomonas aeruginosa. The contamination did not markedly decrease even after
      disinfection with sodium hypochlorite. However, the flesh of each type of peeled
      fruit showed no or only low levels of contamination (<or=10 CFU/g), probably
      caused by the transfer of microorganisms from the skin of fruit via fruit knives.

PMID- 18827353
TI  - Fungicidal effect of piscidin on Candida albicans: pore formation in lipid
      vesicles and activity in fungal membranes.
AB  - Piscidin, a 22-residue cationic peptide isolated from the mast cells of hybrid
      striped bass, has potent antimicrobial activities. In the present study, we
      investigated the fungicidal activity and mode of action of piscidins. Fungicidal
      and hemolytic assays were examined in order to assess their potency and toxicity,
      respectively. The results showed that fungicidal and hemolytic activities were
      higher for piscidin 1 (P1) than piscidin 3 (P3). Additionally, the abilities to
      permeabilize the model phospholipids membranes were also higher for P1 than P3,
      which were consistent with the biological activities of P1 and P3. These results
      suggest that the biological action of the peptides may be carried out through the
      lipid membrane. To understand the fungicidal properties of P1, we focused on a
      membrane-active mechanism of the peptide by in vivo testing against Candida
      albicans as the model organism. Flow cytometric analysis by using bis-(1,3
      dibutylbarbituric acid) trimethine oxonol [DiBAC(4)(3)] and protoplast
      regeneration experiments showed that P1 caused fungal membrane damage.
      Furthermore, fluorescence analysis, using 1,6-diphenyl-1,3,5-hexatriene, revealed
      that these peptides created pores in fungal membranes. Thus, the present study
      demonstrated that piscidins exert their fungicidal effects by disrupting fungal
      membrane through pore formation.

PMID- 18827354
TI  - Effect of tacrolimus on activity and expression of P-glycoprotein and ATP-binding
      cassette transporter A5 (ABCA5) proteins in hematoencephalic barrier cells.
AB  - Tacrolimus is an agent used in clinical immunosuppressive drug therapies. A wide
      spectrum of adverse effects has been reported in association with this
      immunosuppressor, including neurotoxic effect. The upper limit of therapeutic
      blood concentrations of tacrolimus has been described as 30 ng/ml in
      immunosuppressed patients. We investigated the effect of this therapeutic dose of
      tacrolimus on the expression and activity of the multidrug resistance protein 1
      (MDR1 or Pgp, P-glycoprotein) and ATP-binding cassette transporters A5 (ABCA5) in
      human brain microvascular endothelial cells (HBMEC), derived from Blood-Brain
      Barrier (BBB) endothelium, these being the most predominantly expressed
      transcripts in these cells. The expression and activity of MDR1 transporter
      decreased with 30 ng/ml tacrolimus. The cell viability was not changed with the
      therapeutic dose used. By contrast, ABCA5 transcripts, of unknown role as yet,
      increased their expression at this concentration. We propose that the secondary
      cytotoxic effects of this immunosuppressor on CSN, besides the functional
      blockade related to multidrug resistance proteins, such as MDR1, and probably
      ABCA5, could be linked to variations in the expression levels of these proteins
      at the BBB.

PMID- 18827355
TI  - Validation of 13C-acetic acid breath test by measuring effects of loperamide,
      morphine, mosapride, and itopride on gastric emptying in mice.
AB  - Several methods are used to evaluate gastric motility in rodents, but they all
      have technical limitations. Recent technical developments enable a convenient
      method to evaluate gastric motility. The (13)C-acetic acid breath test in rodents
      is a non-invasive and repeatable method that can be used without physical
      restraints. The present study aimed to validate the (13)C-acetic acid breath test
      by measuring the effects of loperamide, morphine, mosapride, and itopride on
      gastric emptying in mice. Loperamide (1-10 mg/kg) and morphine (1.25-10 mg/kg)
      slowed gastric emptying and decreased the maximum concentration (C(max)) and area
      under the curve (AUC(90 min)) value in a dose-dependent manner. Mosapride (0.2-5
      mg/kg) accelerated gastric emptying and increased C(max) value. Mosapride (20
      mg/kg) did not accelerate gastric emptying on the (13)C-breath test. Itopride (30
      mg/kg, per os) significantly accelerated gastric emptying compared with the
      vehicle group. In a comparison with the conventional phenol red test, there was a
      correlation between the C(max) value of breath test and gastric emptying (%) of
      phenol red tests in treatment with loperamide or mosapride. These results
      indicate that the (13)C-acetic acid breath test is an accurate, noninvasive, and
      simple method for monitoring gastric emptying in mice. This method is useful to
      assess the effect of drugs and gut function pharmacologically.

PMID- 18827356
TI  - Protective effects of ginsenoside Rd on PC12 cells against hydrogen peroxide.
AB  - Oxidative stress-induced cell damage has been implicated in a variety of
      neurodegenerative disorders. In the current study, we investigated the protective
      role of ginsenoside Rd against the cytotoxicity induced by exposure to hydrogen
      peroxide (H(2)O(2)) and the underlying mechanism in the PC12 cell line. The
      protective effects of ginsenoside Rd (1, 10 microM) on H(2)O(2)-induced
      cytotoxicity may be ascribed to its antioxidative properties by reducing the
      intracellular reactive oxygen species level; decreasing malondialdehyde
      production, a common index of lipid peroxidation; and enhancing the antioxidant
      enzymatic activities of superoxide dismutase and glutathione peroxidase.
      Additionally, ginsenoside Rd could stabilize the mitochondrial membrane potential
      after H(2)O(2) exposure. These findings suggested that ginsenoside Rd may be
      considered a potential antioxidant agent and should encourage further research in
      neurodegenerative diseases to explore the potential neuroprotective effects of
      ginsenoside Rd.

PMID- 18827357
TI  - Effects of repeated electroconvulsive seizures on spontaneous alternation
      behavior and locomotor activity in rats.
AB  - Epileptic patients are at a significantly higher risk for impairments of
      cognitive function and behavioral abnormalities. In this study, we investigated
      the effect of repeated electroconvulsive shock (ECS)-induced seizures on the
      spontaneous alternation behavior in a Y-maze test and the locomotor activity in
      an open-field test, and examined the effects of anti-epileptic drugs in rats. ECS
      was administered for seven consecutive days and the Y-maze and open-field tests
      were performed 24 h after the last ECS administration. The repeated
      electroconvulsive seizures significantly impaired the spontaneous alternation and
      increased the locomotor activity. Moreover, these behavioral changes induced by
      the seven administrations of ECS persisted for at least 28 d. The inhibition of
      the ECS-induced seizures through the daily pretreatment of the phenytoin (120
      mg/kg, intraperitoneally (i.p.)), phenobarbital (60 mg/kg, i.p.) and valproate
      (400 mg/kg, i.p.) abolished the locomotor hyperactivity in the open-field test.
      The impaired spontaneous alternation behavior in the Y-maze test was also
      significantly suppressed by the treatment with phenytoin and valproate. However,
      phenobarbital injection produced no significant ameliorating effect in the Y-maze
      test. These results suggest that the inhibition of ECS-induced seizures through
      phenytoin and valproate injections suppress the development of impairment of
      spontaneous alternation and the locomotor hyperactivity.

PMID- 18827358
TI  - Possible involvement of long chain fatty acids in the spores of Ganoderma lucidum
      (Reishi Houshi) to its anti-tumor activity.
AB  - During our isolation of biologically active substances from the spores of
      Ganoderma lucidum (Reishi Houshi, G. lucidum) guided by the inhibitory activity
      on HL-60 cell proliferation, NMR spectroscopic and mass spectrometric data
      indicate the substance contains a mixture of several long chain fatty acids.
      Hence, in this study, we have examined the inhibitory effects of an ethanolic
      extract of the spores of G. lucidum as the spore extract, on the proliferation of
      various human cancer cell lines by comparison with several authentic long chain
      fatty acids. Of the fatty acids we examined nonadecanoic acid (C19:0) showed the
      highest inhibitory activity for HL-60 cell proliferation with IC(50) values of
      68+/-7 microM followed by heptadecanoic acid (C17:0, 120+/-23 microM), octa-
      (C18:0, 127+/-4 microM) and hexadecanoic acids (C16:0, 132+/-25 microM),
      respectively. The corresponding unsaturated fatty acids containing one double
      bond such as cis-10-nonadecenoic acid (C19:1), cis-9-octadecenoic acid (C18:1),
      cis-10-heptadecenoic acid (C17:1) and cis-9-hexadecenoic acid (C16:1) were less
      effective. The ethanolic extract of spores of G. lucidum were shown by annexin-V
      FITC/PI double staining to induce apoptosis of HL-60 cells in a similar way to
      cis-10-nonadecenoic acid (C19:1). These unsaturated fatty acids probably inhibit
      tumor necrosis factor production induced by lipopolysaccharide in a mouse
      macrophage preparation. Our results suggest the spores of G. lucidum contain 19
      carbon fatty acids as one of the components for characteristics of its
      physiological effects.

PMID- 18827359
TI  - Anti-inflammatory and immunomodulatory properties of 2-amino-3H-phenoxazin-3-one.
AB  - Accumulating evidence suggests that nitric oxide (NO) and prostaglandin E(2)
      (PGE(2)) are involved in the pathogenesis of various chronic inflammatory
      diseases and cancer. During the course of a screening program to identify natural
      anti-inflammatory substances, we isolated the compound 2-amino-3H-phenoxazin-3
      one (APO) from an extract of the edible brown mushroom Agaricus bisporus IMBACH.
      APO inhibited NO production by mouse peritoneal macrophages in response to the
      pro-inflammatory stimuli lipopolysaccharide (LPS) and interferon (IFN)-gamma
      (LPS/IFN-gamma) at low concentrations (IC(50)=1.5 microM) through reduced
      inducible NO synthase protein expression. PGE(2) production by LPS/IFN-gamma
      stimulated macrophages was inhibited by APO at much lower concentrations
      (IC(50)=0.27 microM) than those required for the inhibition of NO production.
      Mechanistic analysis showed that APO inhibited both cyclooxygenase (COX)-1 and
      COX-2 enzyme activities with almost equal selectivity. Secretion of NO and the
      pro-inflammatory cytokine IL-6 by IFN-gamma-activated RAW264.7 cells, a murine
      macrophage-like cell line, was also dose-dependently reduced by APO. Furthermore,
      APO increased the secretion of the anti-inflammatory cytokine IL-4 by antigen
      stimulated T cells and promoted the polarization of CD4(+) Th cells toward the
      anti-inflammatory Th2 phenotype at equimolar concentrations that inhibited NO
      production. Our results suggested that APO induced polarization toward the Th2
      subset, at least in part through the down-regulation of IL-12 production. Thus,
      APO appears to have potent anti-inflammatory and immunoregulatory properties that
      may provide a promising therapeutic strategy for the treatment of T cell-mediated
      inflammatory autoimmune diseases as well as for bacteria-induced chronic
      inflammatory diseases.

PMID- 18827360
TI  - Extended release dosage form of glipizide: development and validation of a level
      A in vitro-in vivo correlation.
AB  - Defining a quantitative and reliable relationship between in vitro drug release
      and in vivo absorption is highly desired for rational development, optimization,
      and evaluation of controlled-release dosage forms and manufacturing process.
      During the development of once daily extended-release (ER) tablet of glipizide, a
      predictive in vitro drug release method was designed and statistically evaluated
      using three formulations with varying release rates. In order to establish
      internally and externally validated level A in vitro-in vivo correlation (IVIVC),
      a total of three different ER formulations of glipizide were used to evaluate a
      linear IVIVC model based on the in vitro test method. For internal validation, a
      single-dose four-way cross over study (n=6) was performed using fast-, moderate-,
      and slow-releasing ER formulations and an immediate-release (IR) of glipizide as
      reference. In vitro release rate data were obtained for each formulation using
      the United States Pharmacopeia (USP) apparatus II, paddle stirrer at 50 and 100
      rev. min(-1) in 0.1 M hydrochloric acid (HCl) and pH 6.8 phosphate buffer. The
      f(2) metric (similarity factor) was used to analyze the dissolution data. The
      formulations were compared using area under the plasma concentration-time curve,
      AUC(0-infinity), time to reach peak plasma concentration, T(max), and peak plasma
      concentration, C(max), while correlation was determined between in vitro release
      and in vivo absorption. A linear correlation model was developed using percent
      absorbed data versus percent dissolved from the three formulations. Predicted
      glipizide concentrations were obtained by convolution of the in vivo absorption
      rates. Prediction errors were estimated for C(max) and AUC(0-infinity) to
      determine the validity of the correlation. Apparatus II, pH 6.8 at 100 rev. min(
      1) was found to be the most discriminating dissolution method. Linear regression
      analysis of the mean percentage of dose absorbed versus the mean percentage of in
      vitro release resulted in a significant correlation (r(2)>or=0.9) for the three
      formulations.

PMID- 18827361
TI  - The preparation of a lipidic endotoxin affects its biological activities.
AB  - Bacterial membrane constituents, such as Ornithine-containing lipid (OL) and the
      lipid A portion of lipopolysaccharide, trigger various immune responses through
      recognition by Toll-like receptor (TLR) 4. Usually, these lipids are dissolved in
      a small amount of aqueous or organic solvent before being added to the culture
      medium for examination of their biological activities. Macrophages stimulated
      with OL or lipid A sonically dissolved in saline released both interleukin-1beta
      (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha). In contrast, macrophages
      stimulated with OL or lipid A sonically dissolved in ethanol or dimethyl
      sulfoxide (DMSO) secreted much TNF-alpha, but very little IL-1beta. These
      results, taken together, indicate that how an endotoxin is prepared affects its
      biological activities. In addition, electromicroscopic analysis revealed that
      sonication of air-dried OL or lipid A in DMSO produced larger particles than
      those produced in saline, suggesting that the process of preparing lipidic TLR4
      ligands affects their physical state including particle size, and that the
      physical state might be an important determinant of biological activity.

PMID- 18827362
TI  - Troglitazone increases IL-1beta induced cyclooxygenase-2 and inducible nitric
      oxide synthase expression via enhanced phosphorylation of IkappaBalpha in
      vascular smooth muscle cells from Wistar-Kyoto rats and spontaneously
      hypertensive rats.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) agonists of the
      thiazolidinedione class are widely used for the treatment of type 2 diabetes
      subjects due to their ability to improve insulin resistance. Troglitazone and
      ciglitazone belong to the PPARgamma agonists of thiazolidinediones. We report
      here that troglitazone but not ciglitazone increased IL-1beta induced
      cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression in
      vascular smooth muscle cell (VSMC) from Wistar-Kyoto rats (WKY) and spontaneously
      hypertensive rats (SHR). Potentiated expression of COX-2 and iNOS by troglitazone
      was inhibited by MG-132, a specific inhibitor of inhibitory factor kappaB
      (IkappaB) activation. Troglitazone treatment of these cells also resulted in a
      dose-dependent increase in IL-1beta induced IkappaBalpha phosphorylation. These
      data suggest that troglitazone is capable of increasing IL-1beta induced COX-2
      and iNOS expression through an IkappaBalpha dependent mechanism in VSMC from WKY
      and SHR.

PMID- 18827363
TI  - Attenuation of cataract progression by A-3922, a dihydrobenzofuran derivative, in
      streptozotocin-induced diabetic rats.
AB  - The present study was undertaken to assess whether A-3922, a dihydrobenzofuran
      derivative that possesses antioxidative effects, had any preventive effect on the
      onset and/or progression of diabetic cataract. Male Wistar rats were received a
      bolus intravenous injection of streptozotocin (65 mg/kg) and were given 5%
      glucose in drinking water for 10 weeks. The diabetic rats were divided into two
      groups and treated with 30 mg/kg/d A-3922 or vehicle during the experimental
      period. The opacities of eye lenses were observed by using both our original
      device and a slit lamp microscope. The lens opacities were initially detected as
      early as the 2nd week and the cataracts were developed in similar fashion in both
      A-3922-treated and untreated diabetic rats until 7th week, suggesting that A-3922
      did not show any appreciable effect on the onset of diabetic cataract. In the
      later period (8th week or later), however, progression of cataract was retarded
      and significant reductions in both the total cataract score and the degree of
      opacity were apparently observed on 10th week of A-3922-treated diabetic rats.
      These results suggest that A-3922 can delay the progression but not the onset of
      diabetic cataract, and it has a possibility to be a candidate for drugs of
      cataract associated with diabetes.

PMID- 18827364
TI  - Lavandulyl flavanones from Sophora flavescens protect mouse hippocampal cells
      against glutamate-induced neurotoxicity via the induction of heme oxygenase-1.
AB  - Lavandulyl flavanones of Sophora flavescens roots are anti-malarial, anti
      inflammatory, and cytotoxic. Here, we examined whether four lavandulyl
      flavanones, (2S)-2'-methoxykurarinone (1), sophoraflavanone G (2), leachianone A
      (3), and (-)-kurarinone (4), isolated from S. flavescens could protect HT22
      immortalized hippocampal cells against glutamate-induced oxidative stress.
      Compounds 1 and 2 induced the expression of heme oxygenase (HO)-1 and increased
      HO activity dose- and time-dependently. These two compounds also suppressed
      glutamate-induced reactive oxygen species generation in HT22 cells, whereas
      compounds 3 and 4 were not protective. These two lavandulyl flavanones (compounds
      1, 2) may protect against glutamate-induced neurotoxicity via HO-1 induction.

PMID- 18827365
TI  - Protein glycation inhibitors from the fruiting body of Phellinus linteus.
AB  - To characterize active principles for prevention and treatment of diabetic
      complications, the isolation of protein glycation inhibitors from the fruiting
      body of Phellinus linteus was conducted in vitro using the model systems of
      hemoglobin-delta-gluconolactone (early stage), bovine serum albumin-methylglyoxal
      (middle stage), and N(alpha)-acetyl-glycyl-lysine methyl ester-D-ribose (last
      stage) assays. Nine compounds were isolated from the active ethylacetate fraction
      of the fruiting body and identified as protocatechuic acid (1),
      protocatechualdehyde (2), caffeic acid (3), ellagic acid (4), hispidin (5),
      davallialactone (6), hypholomine B (7), interfungins A (8), and inoscavin A (9)
      by spectroscopic analyses. At the early stage of protein glycation, compounds 6,
      8, and 9 exhibited inhibitory activity on hemoglobin A(1C) formation. For the
      middle stage, compounds 2, 6, and 9 showed a significant inhibitory effect on
      methylglyoxal-medicated protein modification and their IC(50) values were 144.28,
      213.15, and 158.66 muM, respectively. At the last stage of glycation, compound 8
      was found to be a potent inhibitor of the cross-linking of proteins, which was
      more effective than that of aminoguanidine, a well-known inhibitor for advanced
      glycation end products. Consequently, compound 8 showed the most potent
      inhibitory effects at each stage of protein glycation. This mechanism may help to
      provide a protective effect against hyperglycemia-mediated protein damage.

PMID- 18827366
TI  - Histamine release inhibitory activity of Piper nigrum leaf.
AB  - Oral administration of a methanolic extract of Piper nigrum leaf (PN-ext, 50, 200
      and 500 mg/kg) showed a potent dose-dependent inhibition of dinitrofluorobenzene
      (DNFB)-induced cutaneous reaction at 1 h [immediate phase response (IPR)] after
      and 24 h [late phase response (LPR)] after DNFB challenge in mice which were
      passively sensitized with anti-dinitrophenyl (DNP) IgE antibody. Ear swelling
      inhibitory effect of PN-ext (50, 200 and 500 mg/kg, per os (p.o.)) on very late
      phase response (vLPR) in the model mice was significant but weaker than that on
      IPR. Oral administration of PN-ext (50, 200 and 500 mg/kg for 7 d) inhibited
      picryl chloride (PC)-induced ear swelling in PC sensitized mice. PN-ext exhibited
      in vitro inhibitory effect on compound 48/80-induced histamine release from rat
      peritoneal mast cells. Two lignans of PN-ext, (-)-cubebin (1) and (-)-3,4
      dimethoxy-3,4-desmethylenedioxycubebin (2), were identified as major active
      principles having histamine release inhibitory activity.

PMID- 18827367
TI  - Purification, physicochemical properties, thermal analysis and antinociceptive
      effect of atranorin extracted from Cladina kalbii.
AB  - Lichens and their secondary metabolites have attracted the interest of many
      researchers. Some species have been shown to contain substances with remarkable
      biologic activity, as antimicrobial, mainly against Gram positive bacteria;
      antineoplasic acting on solid and ascetic tumors, or in culture cells; antiviral;
      hypotensive; and spasmolytic effects. The aim of this study was to isolate and
      characterize atranorin, one of the major constituents which presents in Cladina
      kalbii (DES ABB.) AHTI., and analyze its antinociceptive effect. The
      antinociceptive activity was verified in acetic acid-induced writhing test and
      formalin test with mice. In this work it was observed that atranorin was
      effective in significant reducing (p<0.05) abdominal writhing at doses of 200 and
      400 mg/kg (p.o.) by 52.6 and 61.3%, respectively, when compared to control group
      (vehicle). The formalin test showed in 200 and 400 mg/kg (p.o.) that atranorin
      injection was able to inhibit the inflammatory processes (second phase) dose
      dependently.

PMID- 18827368
TI  - High dosage sildenafil induces hearing impairment in mice.
AB  - Sildenafil is widely administered for the treatment of erectile dysfunction.
      Recently, sensorineural hearing loss following the ingestion of sildenafil was
      reported in one male patient. We examined hearing in mice that were administered
      high doses of sildenafil for up to 105 d. To assess hearing impairment, we
      evaluated auditory brainstem responses, auditory middle latency responses, and
      otoacoustic emissions. At high doses, sildenafil increased the hearing threshold
      shift of auditory brainstem responses. High-dose sildenafil treatment also
      resulted in delayed latency of both auditory brainstem responses and auditory
      middle responses. Otoacoustic emissions differed between control and high-dose
      sildenafil groups with long-term treatment. Collectively, these data demonstrate
      that high-dose and long-term sildenafil administration can induce hearing
      impairment in mice.

PMID- 18827369
TI  - Angiotensin-converting enzyme inhibitors reduce long-term aortic events in
      patients with acute type B aortic dissection.
AB  - BACKGROUND: Medical therapy gives excellent short-term outcomes for patients with
      Stanford type B acute aortic dissection. However, the affected aorta is often
      compromised by aneurysmal dilatation and rupture, resulting in poor long-term
      outcome. The present study investigated which antihypertensive treatment may
      prevent long-term aortic events in these patients. METHODS AND RESULTS: The study
      group comprised 78 consecutive patients with Stanford type B acute aortic
      dissection who were treated medically and followed-up for an average of 873+/-548
      days. The optimal hypertensive drug regimen to reduce aortic events was
      determined by multivariate analyses. Of the 78 patients, 73 (94%) were discharged
      from hospital with medical therapy, and aortic events occurred in 13 (18%) of
      them (aortic rupture/recurrent dissection in 2 (3%); aortic expansion >or=60 mm
      in 7 (10%), rapid aortic expansion >or=10 mm/year in 3 (4%), and development of
      visceral/limb ischemia in 1 (1%)) during follow-up. By multivariate analysis,
      patients given angiotensin-converting enzyme inhibitor (ACEI) were less likely to
      have long-term aortic events than those without (odds ratio: 0.18, 95% confidence
      interval: 0.04-0.85). CONCLUSIONS: Use of ACEI is associated with a reduced risk
      of long-term aortic events in patients with medically treated type B aortic
      dissection.

PMID- 18827370
TI  - Feasibility of intravenous administration of landiolol hydrochloride for
      multislice computed tomography coronary angiography: initial experience.
AB  - BACKGROUND: The feasibility of using landiolol hydrochloride in multislice
      computed tomography (MSCT) coronary angiography (CAG) was investigated in the
      present study. METHODS AND RESULTS: Landiolol hydrochloride was continuously
      administered intravenously to 145 patients before starting MSCT CAG. Hemodynamic
      changes [blood pressure (BP), heart rate (HR)], adverse effects, image quality
      using a 5-point scale, and accuracy of detecting significant stenoses (>or=50%
      reduction in lumen diameter) were evaluated. HR was significantly reduced during
      injection, and quickly recovered after cessation of administration, of landiolol
      hydrochloride. Neither significant changes in BP nor adverse effects occurred.
      Among visible segments, 1,869 (94%) displayed an excellent (83%) or good (11%)
      image quality. Diagnostic accuracy was evaluated in 39 of 145 patients who
      underwent invasive CAG within 3 weeks after MSCT. The sensitivity, specificity,
      positive predictive value, and negative predictive value of MSCT CAG for
      detection of significant stenoses in assessable segments were excellent (per
      artery: 94%, 98%, 92%, and 100%; per segment: 92%, 98%, 94%, and 96%,
      respectively). CONCLUSIONS: Intravenous administration of landiolol hydrochloride
      reduces HR without a significant reduction in BP, which enables favorable image
      quality and diagnostic accuracy without adverse effects, making this agent
      feasible as a premedication for MSCT CAG.

PMID- 18827371
TI  - Risk factors for prolonged mechanical ventilation following surgery for acute
      type a aortic dissection.
AB  - BACKGROUND: The aim of this study was to identify predictors of prolonged
      mechanical ventilation (PMV) following surgery for acute type A aortic dissection
      (AAAD) and to assess the influence of this complication on clinical outcomes.
      METHODS AND RESULTS: A total of 243 patients underwent emergency surgery for AAAD
      in the period of 1997-2006. Ten patients died within 48 h after surgery. The
      remaining 233 patients were divided into 2 groups according to the duration of
      mechanical ventilation; less than 48 h (group A: n=149) or 48 h or longer (group
      B; n=84). Multivariate analysis was used to identify predictors of PMV. Short and
      late outcomes were compared between groups. Multivariate analysis showed that
      shock (systolic BP <90 mmHg; p=0.007), postoperative renal dysfunction
      (creatinine >2.0 mg/dl; p=0.016), coronary artery bypass grafting (CABG)
      (p=0.017), and limb ischemia (p=0.044) were independent predictors of PMV. There
      was no significant difference in in-hospital mortality (group A, 2.7% vs group B,
      3.6%) or 5-year survival (group A, 85.9% vs group B, 76.8%). CONCLUSIONS: Shock,
      limb ischemia, CABG, and postoperative renal dysfunction increase the risk for
      PMV. Knowing the predictors of PMV should help optimize postoperative management
      of these patients.

PMID- 18827372
TI  - Normal values of echocardiographic parameters in relation to age in a healthy
      Japanese population: the JAMP study.
AB  - BACKGROUND: Normal values for echocardiographic measurements and the relationship
      between these parameters and age in a large Japanese population are still
      unknown. METHODS AND RESULTS: A total of 700 healthy Japanese aged 20-79 years
      underwent 2-dimensional and Doppler echocardiography at collaborating
      institutions. The respective mean values obtained in men and women were as
      follows: septal wall thickness, 0.9+/-0.1 and 0.8+/-0.1 cm; posterior wall
      thickness, 0.9+/-0.1 and 0.8+/-0.1 cm; left ventricular (LV) diastolic diameter,
      4.8+/-0.4 and 4.4+/-0.3 cm; LV systolic diameter, 3.0+/-0.4 and 2.8+/-0.3 cm; LV
      diastolic volume, 93+/-20 and 74+/-17 ml; LV systolic volume, 33+/-20 and 25+/-7
      ml; LV ejection fraction, 64+/-5 and 66+/-5%; maximum left atrial (LA) volume,
      42+/-14 and 38+/-12 ml. Aortic root diameter, LV wall thickness, and LV mass
      slightly increased with age, whereas indexed LA volume did not vary with age.
      Diastolic parameters assessed by mitral inflow and mitral annular velocities
      declined with age, as previously reported. CONCLUSIONS: Normal values of
      echocardiographic measurements in a large Japanese population are reported for
      the first time; several systolic and diastolic parameters varied with age. These
      results provide important reference values that should be useful in routine
      clinical practice as well as in clinical trials.

PMID- 18827373
TI  - Multifocal, persistent cardiac uptake of [18-F]-fluoro-deoxy-glucose detected by
      positron emission tomography in patients with acute myocardial infarction.
AB  - BACKGROUND: Inflammation appears to be important in the pathogenesis of acute
      myocardial infarction (AMI). METHODS AND RESULTS: Cardiac [18-F]-fluoro-deoxy
      glucose (FDG) uptake by positron emission tomography/computed tomography (PET/CT)
      scan was investigated in 12 fasting patients with first AMI (FAMI) single-vessel
      disease after successful primary percutaneous coronary intervention and at 9
      weeks follow-up, and in 12 controls. The average FDG uptake (aFDGu) of the 28
      left ventricular (LV) wall segments defined on the PET/CT images of the 12 FAMI
      patients was 1.28+/-0.57-fold higher than the activity present in the LV cavity.
      By contrast, the aFDGu of the 12 controls was 0.70+/-22 (p<0.001). The segmental
      aFDGu in the FAMI was multifocal in both the culprit and non-culprit segments; it
      was less than LV cavity activity in 38%, 1-2-fold greater in 51.8% and more than
      2-fold greater in 10.2%. At follow-up, aFDGu was significantly increased in both
      culprit and non-culprit segments (1.69+/-1.15, p<0.001). Statistically
      significant differences between FAMI and controls patients were only found for
      interleukin-6 plasma levels on admission (11.3+/-7.7 pg/ml vs 2.2+/-1.3 pg/ml;
      p<0.004). CONCLUSION: Multifocal, non-infarct related, cardiac-FDG-uptake
      occurred immediately after AMI and persisted at follow-up. The cause of these
      striking and consistent findings is still speculative.

PMID- 18827374
TI  - Development of new synthetic reactions for nitrogen-containing compounds and
      their application.
AB  - Nitrogen-containing compounds are core parts not only of natural and synthetic
      medicines but also of biologically active compounds including natural products.
      This review focuses on the development of new synthetic reactions for nitrogen
      containing compounds via three methodologies: the reductive photocycloaddition
      reaction of enamides, radical addition reaction, and nucleophilic addition
      reaction. Newly developed reactions were successfully applied to the synthesis of
      various types of nitrogen-containing compounds including medicines, lead
      compounds to new drugs, natural alkaloids, and others.

PMID- 18827375
TI  - Development of novel fast-disintegrating tablets by direct compression using
      sucrose stearic acid ester as a disintegration-accelerating agent.
AB  - It was attempted to produce novel furosemide (FS) fast-disintegrating tablets by
      direct compression. The combination of FS, microcrystalline cellulose,
      croscarmellose sodium and xylitol was used as the basic formulation, and sucrose
      stearic acid ester (SSE) was chosen as an additional additive. The tablets with
      SSE were prepared by the simple addition of SSE, using a lyophilized mixture of
      FS and SSE or using a FS/SSE mixture obtained by evaporation of their ethanol
      solution. Only the tablets, produced using the FS/SSE mixture obtained by organic
      solvent (ethanol) evaporation, showed hardness of more than 30 N and a
      disintegration time of less than 20 s, which were the properties suitable for
      fast-disintegrating tablets. These properties were considered to result from well
      mixed and fine-powdered SSE and FS.

PMID- 18827376
TI  - Quality of twelve clarithromycin dry syrup formulations-bitterness, grittiness
      and uniformity of drug loading.
AB  - The objective of the study was to evaluate the bitterness, grittiness and
      uniformity of drug loading as measures of the quality of 12 formulations of
      clarithromycin dry syrup (CAMDS), comprising one branded and 11 generic products.
      Some of the generic CAMDS formulations were more bitter than the branded product
      while others had similar bitterness when tested as aqueous suspensions. Only one
      generic product was less bitter than the branded product when tested as a
      suspension in acidic sports drink. The usual dissolution test described in JP XV
      could not be used to evaluate the bitterness of the products. A brief dissolution
      test using only 12.5 ml of water was used to evaluate the bitterness of the
      products in aqueous suspensions. There were considerable variances in the
      grittiness of the various products, which were independent of particle size.
      Changes in grittiness level seemed to be correlated with changes in the intensity
      of bitterness due to the disintegration of the formulation. Finally, there was
      less variation in the uniformity of drug loading for the branded product than for
      the generic products. These data may be useful when selecting which CAMDS
      formulation to prescribe.

PMID- 18827377
TI  - Suppression of bitterness and improvement of palatability of commercial
      prednisolone powder.
AB  - The aim of the study was to suppress the bitterness and improve the palatability
      of pediatric prednisolone powder (PP) by the addition of simple sucrose syrup
      (SS) and various beverages and foods. Bitterness suppression was evaluated using
      the human gustatory sensory test. The suppression of the bitterness and
      improvement of palatability of PP by addition of SS solutions was investigated
      using standard taste substances: sucrose for sweetness, tartaric acid for
      sourness, and sodium chloride as saltiness. Dilution with SS solutions of up to
      50% (w/w) was successful in bitterness-suppression and improvement of
      palatability, but at 80% (w/w) SS, the palatability of the diluted solution was
      reduced. The kinematic viscosities of SS solutions were therefore evaluated using
      the Uberorde viscosity meter, to see whether the high viscosity of the more
      concentrated solutions was responsible for the reduced palatability. The
      kinematic viscosity of the 80% SS was 16.60 mm(2)/s. Judging from above
      information, the palatability might become worse when the kinematic viscosity of
      syrup exceeded 15 mm(2)/s. Finally, the ability of various beverages and foods
      with low viscosity to suppress the bitterness and improve the palatability of PP
      were examined. The additions of orange juice or a carbonated lemon drink to
      simple syrup solution were most effective in suppressing bitterness and improving
      palatability of PP.

PMID- 18827378
TI  - Design and synthesis of cinanserin analogs as severe acute respiratory syndrome
      coronavirus 3CL protease inhibitors.
AB  - The severe acute respiratory syndrome (SARS) coronavirus 3CL protease is an
      attractive target for the development of anti-SARS drugs. In this paper,
      cinanserin (1) analogs were synthesized and tested for the inhibitory activities
      against SARS-coronavirus (CoV) 3CL protease by fluorescence resonance energy
      transfer (FRET) assay. Four analogs show significant activities, especially
      compound 26 with an IC(50) of 1.06 microM.

PMID- 18827379
TI  - Stability and stabilization studies of TAK-599 (Ceftaroline Fosamil), a novel N
      phosphono type prodrug of anti-methicillin resistant Staphylococcus aureus
      cephalosporin T-91825.
AB  - TAK-599 (known as ceftaroline fosamil) is a novel N-phosphono type prodrug of a
      cephalosporin compound, T-91825, that exhibits strong activity against
      methicillin resistant Staphylococcus aureus (MRSA). The stability and
      stabilization of TAK-599 were investigated by kinetic analysis focused on
      crystallinity and moisture content. Initially it was planned to develop TAK-599
      as an injectable formulation using the amorphous solid powder prepared by
      lyophilization. However, amorphous of TAK-599 free form was found to be
      chemically unstable even when stored at 8 degrees C, and thus development was
      focused on the crystalline material. After exhaustive screening of
      crystallization condition, the monoacetic acid solvate was found to yield TAK-599
      in a crystalline form. Physicochemical properties were studied to identify the
      key factors affecting the stabilization of TAK-599 in order to improve long-term
      stability, and the results indicated that the crystallinity of TAK-599 correlated
      with stability. Furthermore, moisture content was also identified in our studies
      as an important factor in stabilizing TAK-599. TAK-599 containing about 3%
      moisture was found to be the most stable form. It was concluded that both
      sufficient crystallinity and strict moisture control of TAK-599 were essential to
      maintain long-term stability at 25 degrees C.

PMID- 18827380
TI  - Slow release of tetracycline from a mucoadhesive complex with sucralfate for
      eradication of Helicobacter pylori.
AB  - Treatment composed of a gastric mucoadhesive antibiotic with slow release drug
      delivery is expected to be effective for the eradication of Helicobacter pylori
      (H. pylori). In this study, we evaluated the slow release property of the
      tetracycline-sucralfate acidic complex. Tetracycline was the antibiotic selected
      because of its complexation capacity with sucralfate. Sustained release was
      tested using two different dissolution test methods: paddle and flow-through
      cell. The adhesive paste formed from the acidic complex displayed a longer
      sustained release profile of tetracycline using flow-through cell method. The
      milder conditions of the flow-through cell method better mimicked the fasted
      state of the stomach, suggesting that the oral administration with fasting is
      appropriate for the acidic complex. Furthermore, the paste formation protected
      the tetracycline from decomposition under an acidic condition, which apparently
      contributes to long-term release. Change in the zeta potential of the acidic
      complex particles was helpful in clarifying the release mechanisms of the
      tetracycline. The data indicated that the immediate release of tetracycline in
      the early stage of the test was indispensable to the subsequent paste formation
      that enables slow release. If administrated orally with fasting, the acidic
      complex rapidly adheres to the gastric mucosa and sustains long-term release of
      the tetracycline to the gastric lumen or mucus layer. This antibiotic delivery
      mechanism, which requires only a minimum dosage, may be effective for efficient
      eradication of H. pylori.

PMID- 18827381
TI  - Lipophilicity measurement of drugs by reversed phase HPLC over Wide pH range
      using an alkaline-resistant silica-based stationary phase, XBridge Shield RP(18).
AB  - We propose a reversed phase HPLC (RP-HPLC) with an alkaline-resistant silica
      based stationary phase, XBridge Shield RP(18), for the determination of the
      lipophilicity of drugs with diverse chemical nature ranging from acidic to basic.
      A set of 40 model compounds with well-defined solvatochromic parameters was
      selected to allow a broad distribution of structural properties. The
      chromatographic results showed that the lipophilicity index log k(w) obtained
      with XBridge Shield RP(18) was well correlated with experimental log P(oct)
      values (r(2)=0.96). Linear solvation free-energy relationship (LSER) analyses
      revealed that the retention mechanism of the stationary phase and 1-octanol/water
      partitioning were controlled by almost the same balance of intermolecular forces
      (hydrophobicity as expressed by the van der Waals volume V(w), H-bond acceptor
      basicity beta, and dipolarity/polarizability pi*). The results showed that
      XBridge Shield RP(18) phase overcomes the shortcomings of the silica-based
      stationary phases, the application of which to lipophilicity measurements had
      been limited to neutral and acidic compounds.

PMID- 18827382
TI  - New organoselenium compounds active against pathogenic bacteria, fungi and
      viruses.
AB  - Different N-substituted benzisoselenazol-3(2H)-ones, analogues of ebselen were
      designed as new antiviral and antimicrobial agents. We report their synthesis,
      chemical properties as well as study on biological activity against broad
      spectrum of pathogenic microorganisms (Staphylococcus aureus, Staphylococcus
      simulans, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae,
      Candida albicans, Aspergillus niger) and viruses (herpes simplex virus type 1
      (HSV-1), encephalomyocarditis virus (EMCV), vesicular stomatitis virus (VSV)), in
      vitro. Most of them exhibited high activity against viruses (HSV-1, EMCV) and
      gram-positive bacteria strains (S. aureus, S. simulans), while their activity
      against gram-negative bacteria strains (E. coli, P. aeruginosa, K. pneumoniae)
      was substantially lower. Some of tested compounds were active against yeast C.
      albicans and filamentous fungus A. niger.

PMID- 18827383
TI  - Flavonoid glycosides and other constituents of Psorospermum androsaemifolium
      BAKER (Clusiaceae).
AB  - Two new flavonoid glycosides, namely 3'-(2'',4''-dihydroxybenzyloxy)acanthophorin
      B (1b) and beta,2,3',4,4',6-hexahydroxy-alpha-(alpha-L
      rhamnopyranosyl)dihydrochalcone (2) were isolated from the leaves of Psorospermum
      androsaemifolium together with quercetin (1), acanthophorin B (1a), alpha- (3)
      and beta-amyrine (3a), vismiaquinone (4), 12-hentriacontanol and hentriacontane.
      The structures of these secondary metabolites were established using detailed
      spectroscopic analysis and by comparison with published data. Compounds 1, 1a,
      1b, 2, 3, 3a and 4 showed weak antifungal and antibacterial activities.

PMID- 18827384
TI  - Scale-up studies on high shear wet granulation process from mini-scale to
      commercial scale.
AB  - A newly developed mini-scale high shear granulator was used for scale-up study of
      wet granulation process from 0.2 to 200 L scales. Under various operation
      conditions and granulation bowl sizes, powder mixture composed of anhydrous
      caffeine, D-mannitol, dibasic calcium phosphate, pregelatinized starch and corn
      starch was granulated by adding water. The granules were tabletted, and
      disintegration time and hardness of the tablets were evaluated to seek
      correlations of granulation conditions and tablet properties. As the granulation
      proceeded, disintegration time was prolonged and hardness decreased. When
      granulation processes were operated under the condition that agitator tip speed
      was the same, similar relationship between granulation time and tablet
      properties, such as disintegration time and hardness, between 0.2 L and 11 L
      scales were observed. Likewise, between 11 L and 200 L scales similar
      relationship was observed when operated under the condition that the force to the
      granulation mass was the same. From the above results, the mini-scale high shear
      granulator should be useful tool to predict operation conditions of large-scale
      granulation from its mini-scale operation conditions, where similar tablet
      properties should be obtained.

PMID- 18827385
TI  - Conversion of optically active hydrindanone to (+)-bakkenolide-A.
AB  - A total synthesis of (+)-bakkenolide-A was carried out via the key intermediate
      4, which was prepared based on an asymmetric cyclization-carbonylation reaction
      established in our laboratory. Diastereoselective construction of the
      spirolactone moiety was achieved using Mitsuhashi's protocol as a key step.

PMID- 18827386
TI  - Bioactive constituents from Chinese natural medicines. XXXII. aminopeptidase N
      and aldose reductase inhibitors from Sinocrassula indica: structures of
      sinocrassosides B(4), B(5), C(1), and D(1)-D(3).
AB  - From the methanolic extract of the whole plant of Sinocrassula indica
      (Crassulaceae), six new flavonol glycosides, sinocrassosides B(4) (1), B(5) (2),
      C(1) (3), D(1) (4), D(2) (5), and D(3) (6), were isolated together with 30
      compounds. The structures of 1-6 were elucidated on the basis of chemical and
      physicochemical evidence. In addition, several constituents were found to show
      inhibitory effects on aminopeptidase N and aldose reductase.

PMID- 18827387
TI  - Sesquiterpenes from the roots of Cichorium endivia.
AB  - Twelve new sesquiterpene and sesquiterpene glycosides were obtained along with
      eleven known compounds from the roots of Cichorium endivia (Compositae). The
      compounds were identified as guaianolide, germacrenolide and elemanolide, based
      on spectroscopic methods and chemical evidence.

PMID- 18827388
TI  - The rapid identification of isoflavonoids from Belamcanda chinensis by LC-NMR and
      LC-MS.
AB  - The use of hyphenated LC-NMR and LC-MS techniques for the purpose of directly
      identifying the major constituents of Belamcanda chinensis was investigated.
      Reversed-phase isocratic chromatography was performed using an acetonitrile-water
      solvent system on a C18 column. The NMR spectrum yielded five main peaks, whose
      analysis revealed them to be 5, 6, 7, 3'-tetrahydroxy-4'-methoxyisoflavone (1),
      tectorigenin (2), iristectorigenin A (3), irigenin (4), and irisflorentine (5).
      The identification of these constituents was confirmed by performing LC-ESI-MS
      experiment. This study shows that hyphenated LC-NMR and LC-MS can be used for the
      rapid (70 min) identification of the isoflavonoids.

PMID- 18827389
TI  - Bilayer tablets of atorvastatin calcium and nicotinic acid: formulation and
      evaluation.
AB  - The objective of the study is to formulate bilayer tablets consisting of
      atorvastatin calcium (AT) as an immediate release layer and nicotinic acid (NA)
      as an extended release layer. The immediate release layer was prepared using
      super disintegrant croscarmellose sodium and extended release layer using
      hydroxypropylmethyl cellulose (HPMC K100M). Both the matrix and bilayer tablets
      were evaluated for hardness, friability, weight variation, thickness, and drug
      content uniformity and subjected to in vitro drug release studies. The amount of
      AT and NA released at different time intervals were estimated by HPLC method. The
      bilayer tablets showed no significant change either in physical appearance, drug
      content or in dissolution pattern after storing at 40 degrees C/75% relative
      humiding (RH) for 3 months. The release of the drug from the tablet was
      influenced by the polymer content and it was much evident from
      thermogravimetry/differential thermal analysis (TG/DTA) analysis. The results
      indicated that the bilayer tablets could be a potential dosage form for
      delivering AT and NA.

PMID- 18827390
TI  - Cytotoxic and anti-oxidant activities of lanostane-type triterpenes isolated from
      Poria cocos.
AB  - A new lanostane-type triterpene, 29-hydroxypolyporenic acid C (8), was isolated
      from the dried sclerotia of Poria cocos together with eight other known compounds
      pachymic acid (1), dehydropachymic acid (2), 3-acetyloxy-16alpha
      hydroxytrametenolic acid (3), polyporenic acid C (4), 3-epi-dehydropachymic acid
      (5), 3-epi-dehydrotumulosic acid (6), tumulosic acid (7), and dehydrotumulosic
      acid (9). The compounds were identified by spectral analysis and comparison with
      spectroscopic data reported in the literatures. Although none of the nine (1 to
      9) compounds showed promising antioxidant activity, 1 through 6 and 8 showed good
      cytotoxicity against human lung cancer cell line A549 and human prostate cancer
      cell line DU145. Interestingly, all these compounds exhibited better cytotoxicity
      towards A549 than DU145 cells.

PMID- 18827391
TI  - New chemical constituents of roots of Urtica triangularis HAND-MASS.
AB  - Studies on the chemical constituents of roots of Urtica triangularis HAND-MASS
      have led to the isolation of four new compounds. The structures, including the
      absolute configurations, of these constituents have been elucidated through
      spectral studies including (1)H-NMR, (13)C-NMR, 2D-NMR experiments (heteronuclear
      single-quantum coherence, heteronuclear multiple bonding connectivity and nuclear
      Overhauser effect spectroscopy), high resolution mass spectroscopy (HR-MS) and
      circular dichroism as (-)-4-methoxy-8'-acetyl olivil, (-)-4-methoxy-8'-acetyl
      olivil-4-O-alpha-arabinopyronosyl-(1-->6)-beta-glucopyranoside, (-)-olivil-9-O
      beta-glucopyranoside and cyclo-olivil-9-O-beta-glucopyranoside.

PMID- 18827392
TI  - alpha-glucosidase inhibitors from Garcinia brevipedicellata (Clusiaceae).
AB  - In our continuous search for alpha-glucosidase inhibitors from plants, four new
      depsidones named brevipsidones A-D (1-4) were isolated from stem bark of Garcinia
      brevipedicellata together with known damnacanthal, scopoletin and a mixture of
      stigmasterol and beta-sitosterol. Structural elucidations were made by
      spectroscopic analyses including 2D-NMR data.

PMID- 18827393
TI  - Water-soluble zinc porphyrins as artificial receptors for amino acids.
AB  - The binding of amino acids to water-soluble zinc porphyrins in basic aqueous
      solution was spectrophotometrically analyzed. The amino acids were bound to the
      porphyrins through the coordination of the N atom with the central zinc ion.
      Additional attractions arise due to Coulomb interactions between the -COO(-)
      anion of the amino acids and the -N(CH(3))(3)(+) cation of the porphyrin
      substituents and due to hydrophobic interactions between the porphyrin plane and
      the hydrophobic substituents of the amino acids. These attractions could be
      explained based on the binding data. The compensatory relationships of DeltaS and
      DeltaH were also discussed.

PMID- 18827394
TI  - Malycorins A--C, New lycopodium alkaloids from Lycopodium phlegmaria.
AB  - A novel C(19)N-type Lycopodium alkaloid, malycorin A (1) consisting of a
      serratinane skeleton with 2-propanol unit has been isolated from the club moss
      Lycopodium phlegmaria, together with two new C(16)N-type alkaloids, malycorins B
      (2) and C (3), and the structures and relative stereochemistry were elucidated on
      the basis of spectroscopic data.

PMID- 18827395
TI  - Two new compounds from Dendrobium candidum.
AB  - Two new compounds were isolated from the stems of Dendrobium candidum: (R)-3,4
      dihydroxy-5,4',alpha-trimethoxybibenzyl (1), named dendrocandin A; and 4-[2
      [(2S,3S)-3-(4-hydroxy-3,5-dimethoxyphenyl)-2-hydroxymethyl-8-methoxy-2,3
      dihydrobenzo[1,4]dioxin-6-yl]ethyl]-1-methoxyl benzene (2), dendrocandin B. Five
      previously known bibenzyls were also identified: 4,4'-dihydroxy-3,5
      dimethoxybibenzyl (3), 3,4-dihydroxy-5,4'-dimethoxybibenzyl (4), 3-O
      methylgigantol (5), dendrophenol (6), and gigantol (7).

PMID- 18827396
TI  - Meldrum's acid catalyzed reaction of tetracyanoethylene and aldehydes in water: a
      novel approach to arylidenemalononitrile.
AB  - Meldrum's acid catalyzed the reaction of tetracyanoethylene with aromatic,
      heteroaromatic, and conjugated aldehydes led to arylidenemalononitrile in water
      in good yields at 80 degrees C. The work-up of reactions is very simple and the
      crude products are sufficiently pure to be used without further purification. The
      procedure provides an alternative method for the synthesis of
      arylidenemalononitrile.

PMID- 18827397
TI  - New Guaiane Sesquiterpenes from the Fruits of Torilis japonica.
AB  - Three new guaiane type sesquiterpenes were isolated from the methanolic extract
      of the fruits of Torilis japonica together with a known compound, torilin (1).
      Their structures were established as 11-acetoxy-8-isobutyryl-4-guaien-3-one (2),
      11-acetoxy-8-methacrylyl-4-guaien-3-one (3), and 11-acetoxy-8-propionyl-4-guaien
      3-one (4) by spectroscopic methods. These compounds inhibited lipopolysaccharide
      (LPS)-induced nitric oxide production in murine macrophages RAW 264.7 cells.

PMID- 18827398
TI  - Synthesis, anti-bacterial and anti-oxidant properties of thiadiazaphosphol-2
      ones.
AB  - 4-Amino-5-phenyl-4H-1,2,4-triazole-3-thiol (1) underwent facile condensation with
      various phosphorus dichlorides (2a-j) in the presence of triethylamine in dry
      tetrahydrofuran at 60-65 degrees C and afforded corresponding thiadiazaphosphol-2
      ones (3a-j). Their chemical structures were characterized using IR, (1)H-, (13)C
      , (31)P-NMR and Mass spectral studies. All the title compounds were screened for
      antioxidant properties by radical scavenging methods such as 1,1-diphenyl-2
      picryl hydrazyl (DPPH), hydroxyl and lipid peroxidation. They exhibited potent in
      vitro antioxidant activity dose dependently. Their bioassay showed them to
      possess significant antibacterial activity.

PMID- 18827399
TI  - Structural development of benzhydrol-type 1'-acetoxychavicol acetate (ACA)
      analogs as human leukemia cell-growth inhibitors based on quantitative structure
      activity relationship (QSAR) analysis.
AB  - Benzhydrol-type analogs of 1'-acetoxychavicol acetate (ACA) were developed as
      inhibitors of human leukemia HL-60 cell growth based on quantitative structure
      activity relationship (QSAR) analysis. An analog containing an anthracenyl moiety
      (8) was a potent inhibitor with the IC(50) value of 0.12 microM.

PMID- 18827400
TI  - Synthesis of dibenzofurans directly from aryl halides and ortho-bromophenols via
      one-pot consecutive SNAr and intramolecular palladium-catalyzed aryl-aryl
      coupling reactions.
AB  - A series of dibenzofurans were efficiently and conveniently synthesized via one
      pot consecutive C(sp(2))-O bond formation reaction (SNAr) in the presence of
      anhydrous K(2)CO(3), followed by C(sp(2))-C(sp(2)) bond formation reaction
      (intramolecular palladium-catalyzed aryl-aryl coupling reaction) between aryl
      halides and ortho-bromophenols. The desired dibenzofurans were obtained in 32-99%
      isolated yields.

PMID- 18827401
TI  - A new steroidal glycoside and a new phenyl glycoside from a ripe cherry tomato.
AB  - A new steroidal glycoside and a new phenyl glycoside have been isolated from a
      ripe cherry tomato [Lycopersicon esculentum var. cerasiforme (DUNAL) ALEF.,
      Solanaceae] along with two known steroidal alkaloid glycosides, esculeoisides A
      and B, and five aromatic compounds, zizibeoside I, benzyl alcohol beta
      gentiobioside, rutin, methyl caffeate, and phenylalanine. Their chemical
      structures were determined on the basis of spectroscopic data as well as chemical
      evidence.

PMID- 18827402
TI  - Rhodium catalyzed 1,4-conjugate addition of 1,5-azastibocines with electron
      deficient olefins.
AB  - The rhodium-catalyzed reaction of Sb-aryl-1,5-azastibocines with alpha,beta
      unsaturated ketones and esters is described. Exclusive formation of 1,4-conjugate
      adduct was achieved in aqueous NMP (N-methyl-2-pyrrolidinone) in the presence of
      5 mol% of [RhCl(cod)](2), and no formation of Heck adduct was observed in this
      condition. Reactions with various enones and enoates were also demonstrated to
      prove generality of the 1,4-conjugate addition.

PMID- 18827403
TI  - Migratory localization of cyclin D2-Cdk4 complex suggests a spatial regulation of
      the G1-S transition.
AB  - The association of the cyclin D-Cdk (DC) complex with retinoblastoma protein
      (pRb) is required for the G1-S transition of the cell cycle. Cyclin synthesis,
      nuclear localization and degradation are control mechanisms for the transition,
      but regulation of the DC complex nuclear import also contributes to the
      transition. Analysis of the timing of the G1-S transition in mammalian cell lines
      revealed acceleration with overexpression of cyclin D2 and Cdk4.
      Immunolocalization assays revealed that cyclin D2 and Cdk4 formed a complex in
      the cytoplasm and approached the nucleus. They accumulated on the cytosolic
      surfaces of the nuclear pores and then were arrested at the nuclear membrane
      before the nucleus reached a critical size. Finally, the complex was released
      into the nucleus and colocalized with pRb there, which led to pRb phosphorylation
      and DNA synthesis. The translocalization depended on the G1-S transition. In
      contrast, a truncated cyclin D2 that was not able to fully associate with Cdk4
      lost the ability for release into the nucleus. This pattern of translocalization
      suggests a spatial separation of the cyclin D-Cdk complex from pRb and DNA in the
      nucleus to regulate the G1-S transition.

PMID- 18827404
TI  - SYP71, a plant-specific Qc-SNARE protein, reveals dual localization to the plasma
      membrane and the endoplasmic reticulum in Arabidopsis.
AB  - SNAREs ('Soluble N-ethyl-maleimide sensitive factor attachment protein
      receptors') play a critical role in the membrane fusion step of the vesicular
      transport system in eukaryotes. The number of the genes encoding SNARE proteins
      is estimated to be 64 in Arabidopsis thaliana. This number is much larger than
      those in other eukaryotes, suggesting a complex membrane trafficking in plants.
      The Arabidopsis SNAREs, the SYP7 group proteins, SYP71, SYP72, and SYP73, form a
      plant-specific SNARE subfamily with not-yet-identified functions. We have
      previously reported that the SYP7 subfamily proteins are predominantly localized
      to the endoplasmic reticulum in the Arabidopsis suspension cultured cells under
      transient expression condition. However, several proteomic analyzes indicated the
      plasma membrane localizations of one of SYP7 subfamily proteins, SYP71. In order
      to confirm the expression patterns and subcellular localization of SYP7, we
      performed combination analyses including promoter GUS analysis, a sucrose density
      gradient centrifugation analysis, as well as an observation on transgenic
      Arabidopsis plants expressing GFP-fused SYP71 under control of its native
      promoter. From these analyses, we concluded that one of the SYP7 subfamily
      proteins, SYP71, is predominantly expressed in all vegetative tissues and mainly
      localized to the plasma membrane. We also found that SYP71 is localized to the
      endoplasmic reticulum in the dividing cells of various types of tissues.

PMID- 18827405
TI  - MicroRNA-206 is highly expressed in newly formed muscle fibers: implications
      regarding potential for muscle regeneration and maturation in muscular dystrophy.
AB  - miR-1, miR-133a, and miR-206 are muscle-specific microRNAs expressed in skeletal
      muscles and have been shown to contribute to muscle development. To gain insight
      into the pathophysiological roles of these three microRNAs in dystrophin
      deficient muscular dystrophy, their expression in the tibialis anterior (TA)
      muscles of mdx mice and CXMD(J) dogs were evaluated by semiquantitative RT-PCR
      and in situ hybridization. Their temporal and spatial expression patterns were
      also analyzed in C2C12 cells during muscle differentiation and in cardiotoxin
      (CTX)-injured TA muscles to examine how muscle degeneration and regeneration
      affect their expression. In dystrophic TA muscles of mdx mice, miR-206 expression
      was significantly elevated as compared to that in control TA muscles of age
      matched B10 mice, whereas there were no differences in miR-1 or miR-133a
      expression between B10 and mdx TA muscles. On in situ hybridization analysis,
      intense signals for miR-206 probes were localized in newly formed myotubes with
      centralized nuclei, or regenerating muscle fibers, but not in intact pre
      degenerated fibers or numerous small mononucleated cells, possibly proliferating
      myoblasts and inflammatory infiltrates. Similar increased expression of miR-206
      was also found in C2C12 differentiation and CTX-induced regeneration, in which
      differentiated myotubes or regenerating fibers showed abundant expression of miR
      206. However, CXMD(J) TA muscles contained smaller amounts of miR-206, miR-1, and
      miR-133a than controls. They exhibited more severe and more progressive
      degenerative alterations than mdx TA muscles. Taken together, these observations
      indicated that newly formed myotubes showed markedly increased expression of miR
      206, which might reflect active regeneration and efficient maturation of skeletal
      muscle fibers.

PMID- 18827406
TI  - Serum concentrations of BNP and ANP in patients with thyrotoxicosis.
AB  - Serum BNP (brain naturiuretic peptide) and ANP (atrial natriuretic peptide)
      levels are reportedly elevated in patients with thyrotoxicosis. The increases may
      not be due to thyrotoxicosis itself but to secondary cardiovascular changes such
      as chronic heart failure (HF) or atrial fibrillation (AF) which frequently
      accompany thyrotoxicosis. We measured serum ANP and BNP levels in 130 patients
      with thyrotoxicosis and correlated them with HF severity and thyroid function.
      Thirty-seven normal subjects served as controls. Serum BNP levels in thyrotoxic
      patients were significantly higher than those in control subjects and
      significantly correlated with serum free T4, free T3 and ANP levels. In untreated
      Graves' disease serum BNP level was significantly elevated in patients with HF or
      AF. Multiple regression analysis revealed that HF, free T4, female gender and AF
      are independent contributing factors to the elevated BNP level, and that these
      four factors contributed about 40%. On the other hand, HF and AF were
      contributing variables for ANP level but the overall contribution of these
      factors was only 10%. After normalization of thyroid function, serum BNP levels
      were normalized in 70.5% of Graves' patients. BNP level in euthyroid state was
      dependent on the presence of HF and the BNP value before therapy, but not on
      thyroid hormone levels or AF. These data suggest that the cardiovascular
      condition is the major factor responsible for the elevated serum BNP and ANP
      levels in thyrotoxic patients, while thyrotoxicosis itself is an independent but
      minor contributing factor. Thus, the determination of serum BNP levels in
      thyrotoxic patients is useful for monitoring cardiovascular conditions of HF.

PMID- 18827407
TI  - Nuclear receptor DAX1 in human prostate cancer: a novel independent biological
      modulator.
AB  - The orphan nuclear receptor DAX1 (dosage-sensitive sex reversal-AHC critical
      region on the X chromosome gene 1; NR0B1) has been known for its various roles in
      human development, specifically sex determination and steroidogenesis. Its
      expression has been reported in endocrine and sex steroid-dependent neoplasms
      such as human adrenocortical, pituitary, endometrial, and ovarian tumors.
      Prostate cancer is also sex steroid-dependent tumor in which androgens play
      important roles in the pathogenesis and development via androgen receptor (AR).
      DAX1 is also reported to repress AR activity in human prostate cancer cell line
      (LNCaP) but its biological roles have remained unclear in the human prostate
      cancer. The aim of this study is to examine the expression of DAX1 in human
      prostate cancer using immunohistochemistry in order to evaluate its possible
      biological and/or clinical significance. In this study, we examined the DAX1
      immunoreactivity in human prostate cancer obtained from surgery (n = 40), and
      correlated the findings with clinicopathological features of the patients. Twenty
      one cases were defined as positive cases for DAX1 immunoreactivity (53%).
      Immunoreactivity for DAX1 was inversely and significantly correlated with Gleason
      score (P<0.05). However, DAX1 immunoreactivity was not significantly correlated
      with the status of sex steroid receptors we examined. DAX1 immunoreactivity is
      considered a new biological modulator of human prostate cancer, but independent
      to the status of sex steroid receptors in human prostate cancer tissues.

PMID- 18827408
TI  - A boy with growth disturbance caused by hypothalamic damage associated with
      intracranial hypotension syndrome following a motor vehicle accident: case
      report.
AB  - We examined the endocrine profile of a boy aged 10 years and 4 months with
      intracranial hypotension syndrome (IHS) following a motor vehicle accident. His
      complaint was growth disturbance. GH secretion gradually decreased and finally
      was lost in spite of an epidural blood patch procedure. His height velocity was
      restored by GH replacement therapy. MRI and SPECT revealed damage to the
      hypothalamic and pituitary gland. We concluded that growth disturbance is an
      important sign in pediatric patients with hypothalamic damage associated with
      IHS.

PMID- 18827409
TI  - Hepatocarcinogenesis following HCV RNA eradication by interferon in chronic
      hepatitis patients.
AB  - OBJECTIVE: Interferon (IFN) therapy reduces the incidence of hepatocarcinogenesis
      in patients with hepatitis C viral (HCV) infection who achieve a sustained
      virological response (SVR). The aim of the present study was to determine the
      rate of hepatocarcinogenesis and the risk factor in sustained virological
      responders. PATIENTS AND METHOD: The study subjects were 1,193 patients with HCV
      related chronic liver disease and IFN- or IFN plus ribavirin-induced SVR. The
      age, male/female ratio, and liver fibrosis stage [(F0-F3)/LC] were 15-83 years,
      808/385, and 1106/41, respectively. Patients were followed-up for 8.3 years
      (range, 0 to 19.0 years) and the incidence of hepatocellular carcinoma was
      recorded. RESULTS: Hepatocellular carcinogenesis was detected in 23 patients
      during the follow-up. The crude rates of hepatocarcinogenesis at 5, 10, and 15
      years were 1.5%, 2.4% and 4.1%, respectively. Multivariate analysis identified
      cirrhosis, male sex and age older than 50 years as determinants of
      hepatocarcinogenesis with hazard ratios of 12.9 (p<0.001), 6.45 (p=0.012), and
      20.2 (p=0.004), respectively. CONCLUSION: Long-term follow-up of patients with
      chronic HCV infection is necessary even in those who show SVR, especially in male
      elderly patients with cirrhosis.

PMID- 18827410
TI  - Analysis of thiopurine S-methyltransferase genotypes in Japanese patients with
      inflammatory bowel disease.
AB  - BACKGROUND AND AIMS: Myelosuppression observed in patients with inflammatory
      bowel disease (IBD) treated with azathioprine (AZA) has been attributed to low
      thiopurine S-methyltransferase (TPMT) activity. TPMT activity is dependent on the
      genetic polymorphism of high-versus low-metabolizing alleles. We investigated the
      association between TPMT genotypes and myelosuppression in Japanese IBD patients.
      METHODS: Forty-one healthy volunteers and 70 IBD patients (UC, n = 50; CD, n =
      20) were recruited. All IBD patients were treated with AZA. The TPMT genotypes
      were determined by polymerase-chain reaction-restriction fragment length
      polymorphism (PCR-RFLP) analyses. RESULTS: One healthy volunteer showed a
      heterozygous mutation of TPMT*1/*3C. All other volunteers and the 70 IBD patients
      were of the wild alleleotype (TPMT*1/*1). In the IBD patients, 7 patients
      developed leucopenia (<3,000/microL). One of them developed severe leucopenia
      (<1,000 microL) with agranulocytosis on day 14 after drug initiation. CONCLUSION:
      TPMT mutations are not associated with myelosuppression in Japanese IBD patients.
      Even in IBD patients with a wild TPMT genotype, clinicians should pay attention
      for the possible development of myelosuppression.

PMID- 18827411
TI  - The anatomical distribution of colorectal cancer in Korea: evaluation of the
      incidence of proximal and distal lesions and synchronous adenomas.
AB  - OBJECTIVE: The incidence of colorectal cancer throughout the Republic of Korea
      has been rising over the last 25 years. The change in incidence is supposed to be
      due to the westernized life style. We evaluated the anatomical distribution of
      colorectal cancer and the properties of synchronous adenomatous polyps in the
      Korean population which were known to be different from those in Western
      countries. MATERIALS AND METHODS: From January 1997 to December 2006, 896 cases
      of colorectal cancer were reviewed retrospectively. RESULTS: A total of 25.1%
      were proximally located cancer with a modest female predominance (odds ratio
      1.5). Synchronous adenomatous lesions were accompanied in 31.9% of all colorectal
      cancer cases. In the distal colorectal cancer patients, 18.8% had proximally
      located synchronous adenomas. In those with proximal colon cancer, only 20.5% of
      patients had distally located adenomas. The likelihood of a proximal colon cancer
      without distal sentinel lesions was higher in females (odds ratio 3.0).
      CONCLUSION: There has been a steep rise in the incidence of colorectal cancer in
      Korea and distal colon cancer is more prevalent than in Western countries.
      However, as over 20% of proximal colon cancers can exist without distal colonic
      synchronous or sentinel lesions, a total colonoscopic examination should be
      considered first in surveillance.

PMID- 18827412
TI  - Influence of living style and situation on the compliance of taking
      antihypertensive agents in patients with essential hypertension.
AB  - BACKGROUND: As the reason for insufficient control of blood pressure (BP), poor
      compliance of taking antihypertensive agents is an important issue. In Japan, no
      prospective study on the compliance of antihypertensive agents has been done. In
      this study we prospectively investigated the details of the relationship between
      the compliance of taking antihypertensive agents and living style and situation
      in hypertensive patients. METHODS: We prospectively examined 121 outpatients with
      essential hypertension treated with antihypertensive agents for 12 months. Using
      an oral interview based on the questionnaire sheet, the factors about living
      style and situations which worsen the compliance were assessed. Also we evaluated
      the relationship of BP control and season, which was compared between patients
      with poor compliance and those with good compliance. RESULTS: As for the
      background of the poor compliance, many factors related to the patients' living
      style and situation were clarified. On average for 12 months the levels of the
      compliance and BP showed a significant negative correlation and BP was
      significantly higher in patients with poor compliance than those with good
      compliance. However, in the summer season BP did not differ between patients with
      poor and good compliance, CONCLUSION: Many factors regarding the patients' living
      style and situation were related to poor compliance. The development of strategy
      that changes these factors is a future task for improving compliance. This study
      may also imply that unnecessary antihypertensive agents are prescribed in some
      patients with poor compliance in the summer season. Determination of the suitable
      prescription by which to attain optimal individual patients' compliance is
      important in the treatment of hypertensive patients.

PMID- 18827413
TI  - Initial and mid-term outcomes of pulse infusion thrombolysis using a unique pump
      system and stent placement for deep vein thrombosis.
AB  - OBJECTIVE: The aim of this study was to evaluate the initial and mid-term results
      of pulse infusion thrombolysis (PIT) using a unique pump system and stent
      placement for proximal deep vein thrombosis (DVT) in Japanese. METHODS: Among the
      patients who were admitted to our institute under diagnosis of proximal DVT
      between April 2001 and March 2005, 11 patients (4 men, mean age 61 years) who
      underwent PIT and angioplasty followed by stent placement were enrolled in this
      retrospective analysis. Urokinase or monteplase was used as a thrombolytic agent.
      Venous or stent patency was assessed by color Doppler ultrasound or enhanced
      computed tomography for a mean follow-up duration of 54 months. RESULTS: Sites of
      thrombus were left lower limbs in 10 cases and left upper limb in one case.
      Initial technical (complete venous flow recovery) and clinical (disappearance of
      pain and swelling of diseased leg or arm) success was achieved in all patients.
      Two of 11 patients showed stent occlusion with leg swelling and pain one month
      later and 3 years later, respectively. These patients had associated protein S
      deficiency. CONCLUSION: PIT and stent deployment for DVT is safe and effective
      with favorable initial and mid-term clinical results and without major
      complications in Japanese, except for cases of congenital coagulation
      abnormality.

PMID- 18827414
TI  - Clinical utility of pleural fluid NT-pro brain natriuretic peptide (NT-proBNP) in
      patients with pleural effusions.
AB  - BACKGROUND: Pleural effusion is not a pathognomonic sign and distinguishing
      between transudates and exudates often presents a diagnostic dilemma. OBJECTIVE:
      To examine whether the NT pro-brain natriuretic peptide (NT-proBNP) in pleural
      fluid is a diagnostic tool for determining the cardiac etiology of pleural
      effusions. METHODS: We measured pleural fluid and serum NT-proBNP levels in a
      consecutive series of 98 patients with heart failure and in 142 patients with
      other causes. RESULTS: The median pleural fluid NT-proBNP levels among the heart
      failure patients were significantly higher (3,310 pg/mL) than hepatic hydrothorax
      (16 patients, 531 pg/mL), malignant pleural effusion (38 patients, 733 pg/mL),
      parapneumonic pleural effusion (40 patients, 294 pg/mL), and tuberculous pleural
      effusion (64 patients, 214 pg/mL) (p<0.001). At a cut-off point of > or = 1,714
      pg/mL, the test had a sensitivity of 99%, a specificity of 99 % for the diagnosis
      of heart failure. There were 28 patients with pleural effusion due to heart
      failure misclassified as exudates by Light's criteria. Ten cases of misclassified
      heart failure (36% of 28 patients) showed serum-effusion protein gradient less
      than 3.1 g/dL; 26 of them exhibited pleural fluid NT-proBNP levels of > or =
      1,714 pg/mL. The 26 patients of misclassified heart failure received diuretics
      before thoracentesis. Pleural fluid NT-proBNP levels were correlated with serum
      NT-proBNP levels (R(2)=0.928, p<0.001). CONCLUSION: Pleural fluid NT-proBNP may
      be useful in the diagnosis of pleural effusion resulting from heart failure. The
      test may be especially useful in heart failure patients with exudates who have
      been treated with diuretics.

PMID- 18827415
TI  - An autopsy case of Sjogren's syndrome with acute encephalomyelopathy.
AB  - OBJECTIVE: This study was to clarify the neuropathological findings of acute
      encephalomyelopathy with Sjogren's syndrome. METHODS: We examined an autopsied
      case of acute encephalomyelopathy with Sjogren's syndrome. CASE REPORT: A 40-year
      old woman developed acute myelopathy and brainstem dysfunction. Magnetic
      resonance imaging (MRI) revealed high-intensity lesions on T2-weighted axial
      images (T2WI) in the medulla oblongata and cervical spinal cord. We established a
      diagnosis of Sjogren's syndrome (SjS) according to the European Community
      criteria. The patient was treated with intravenous methylprednisolone (500
      mg/day) for three days, followed by oral prednisolone. Although her neurological
      symptoms improved, her general condition deteriorated after the onset of acute
      colonic pseudo-obstruction and she died of multiple organ failure associated with
      hemophagocytosis. RESULTS: Autopsy showed atrophy of the secretory glands and an
      accumulation of lymphocytes around the ducts, confirming the diagnosis of
      Sjogren's syndrome. Neuropathological examination revealed multifocal lesions in
      the cervical spinal cord and medulla, along with scattered perivascular
      lymphocytic infiltration. In addition, there was demyelination, spongy change and
      axonal swelling in the white matter, but no remarkable vasculitic changes were
      seen in the central nervous system. CONCLUSION: Although the steroid therapy may
      have had a significant influence, the main pathological finding in this case was
      not vasculitis, but rather axonal degeneration with spongy change and axonal
      swelling.

PMID- 18827416
TI  - Cerebral oxygenation monitoring for detecting critical cerebral hypoperfusion in
      patients with multiple system atrophy during the head-up tilt test.
AB  - OBJECTIVE: Near infrared spectroscopy (NIRS) is a non-invasive optical technique
      to monitor cerebral tissue oxygen saturation (ScO(2)). The purpose of this study
      was to reveal the usefulness of ScO(2) monitoring in evaluating cerebral
      circulation in patients with autonomic failure. METHODS: Nineteen patients with
      multiple system atrophy (MSA), who had autonomic failure, and 10 age-matched
      normal control subjects participated. In addition to blood pressure monitoring,
      ScO(2) was recorded by a near-infrared spectroscopy instrument during head-up
      tilt (HUT) test. RESULTS: HUT tests induced postural symptoms in 9 MSA patients
      (presyncopal group), but not in 10 MSA patients (non-presyncopal group) or in any
      of the controls. ScO(2), which decreased slightly in the controls and MSA
      patients, did not differ significantly between the MSA and control groups. With
      regard to MSA subgroups, the ScO(2) reduction in the presyncopal group (-3.1+/
      1.7%) was significantly larger than in the non-presyncopal group (-0.9+/-0.5%,
      P<0.005) and controls (-1.1+/-1.0%, P<0.05). The systolic blood pressure
      decreases during HUT in the non-presyncopal (-35.2+/-16.1 mmHg, P<0.01) and
      presyncopal (-54.3+/-27.5 mmHg, P<0.0005) groups were significantly greater than
      that in the control group (4.0+/-10.7 mmHg), but the difference between
      presyncopal and non-presyncopal groups was not significant. CONCLUSION: In our
      study, ScO(2) reduction seemed to be associated with presyncopal symptoms. ScO(2)
      monitoring may be useful to detect cerebral hypoperfusion in MSA patients with
      autonomic failure.

PMID- 18827417
TI  - Liver atrophy and portal stenosis in two cases of sclerosing cholangitis
      associated with autoimmune pancreatitis.
AB  - Sclerosing cholangitis with autoimmune pancreatitis (SC with AIP) takes a better
      clinical course than primary sclerosing cholangitis due to the effectiveness of
      steroid therapy. However, the morphological and functional changes in SC with AIP
      during long-term observation have not yet been reported. We encountered two cases
      of SC with AIP that resulted in liver atrophy and portal obstruction during long
      term observation. One case was followed up without steroid therapy. The other
      case was treated with endoscopic biliary drainage initially. These cases may
      provide further information regarding steroid therapy for SC with AIP.

PMID- 18827418
TI  - Removal of a foreign body (artificial tooth) from the bronchial tree: a new
      method.
AB  - A 70-year-old man who had aspirated an artificial tooth during treatment at a
      dental clinic visited our hospital. His symptoms and physical condition were not
      remarkable. CT of chest revealed a foreign body in the right middle bronchus;
      bronchoscopy revealed it was wedged there. First, the authors tried to remove it
      using a suction device attached to a bronchoscope, as well as by using a forcep;
      however, the attempt failed. Therefore, a second effort was made using a cap
      constructed of a nasogastric tube, based on the concept of attaching an
      endoscopic cap to a bronchoscope. The latter was successful.

PMID- 18827419
TI  - Likely tuberculous myocarditis mimicking an acute coronary syndrome.
AB  - Acute systemic infections may involve the heart, mostly represented by
      myocarditis and pericarditis. We report the case of a likely myopericarditis in
      an adult, leading to the diagnosis of tuberculosis infection. The clinical
      presentation was an acute coronary syndrome with elevated troponin Ic. An
      alternative diagnosis of myopericarditis was considered. Chest X-ray depicted a
      miliary pattern and a CT-scan demonstrated bilateral micronodules with a "tree-in
      bud" pattern associated with parenchymal consolidations in the apical segment of
      the left upper lobe, suggesting infectious bronchiolitis. As the direct
      microscopic examination of the bronchial expectoration revealed the presence of
      Koch's bacterium, a diagnosis of a tuberculous myocarditis was likely. The
      clinical, electrocardiographic and CT-scan findings are shown; cardiac effects
      associated with tuberculosis are discussed.

PMID- 18827420
TI  - Severe respiratory failure and torsades de pointes induced by disopyramide in a
      patient with myasthenia gravis.
AB  - Class 1a anti-arrhythmic drugs are often used for the treatment of atrial
      fibrillation (AF), but it is not well known that myasthenia gravis (MG)-like
      symptoms can be generated by their anti-cholinergic effects. We had a patient
      with MG who developed symptomatic MG aggravation after AF treatment with
      disopyramide. Symptomatic MG aggravation was followed by Takotsubo-shaped
      cardiomyopathy, QT prolongation, and torsades de pointes. We suggest that the
      anti-cholinergic effects of disopyramide can induce MG crisis and should
      therefore be carefully considered when disopyramide is used to treat AF in
      patients with MG.

PMID- 18827421
TI  - Transformation of p53-positive papillary thyroid carcinoma to anaplastic
      carcinoma of the liver following postoperative radioactive iodine-131 therapy.
AB  - Multiple liver metastases were incidentally detected in the lobe of the liver of
      an 81-year-old woman following total thyroidectomy and ablative radioactive
      iodine administration for the treatment of papillary thyroid carcinoma. A biopsy
      specimen taken from the metastatic liver tumor was histologically diagnosed as
      anaplastic carcinoma. Immunohistochemical staining for p53 was positive in both
      the primary tumor and liver biopsy specimens. We considered this to have been
      caused by anaplastic transformation from papillary thyroid carcinoma during
      treatment. We report a rare case of multiple liver metastases from a papillary
      thyroid carcinoma, which we believe to be the result of anaplastic transformation
      during postoperative radioactive iodine-131 therapy.

PMID- 18827422
TI  - Obesity-related nephropathy associated with a history of IgA nephropathy.
AB  - This report describes the case of a 57-year-old man who underwent a repeated
      renal biopsy 25 years after the first biopsy in which the diagnosis of IgA
      nephropathy was made. Although the patient exhibited gradually increasing
      proteinuria and a slowly progressive renal impairment, the histological findings
      of the repeat biopsy revealed no evidence of either glomerular inflammatory
      changes or IgA deposition. Instead, a marked decrease in the glomerular density
      and hypertrophy of the remnant glomeruli were noted. Almost a complete
      disappearance of urinary protein excretion by a calorie-restricted diet indicated
      that the patient's obesity and its related factors may have contributed to the
      present nephropathic development.

PMID- 18827423
TI  - Huge mediastinal mass with SVC syndrome accompanying numerous chest wall
      collateral vessels.
AB  - A 47-year-old man was referred to our hospital because of dyspnea, cough and
      weight loss. On physical examination, marked dilatation of thoraco-superficial
      epigastric venous anastomosis was found. The chest wall collateral vessels
      revealed enlarged head-to-toe flow, suggesting complete obstruction of the SVC
      and one or more of the major caval tributaries, including the azygos system.
      Thoracic CT demonstrated that a huge anterior mediastinal tumor completely
      obstructed the superior vena cava. He was diagnosed with Hodgkin lymphoma of the
      nodular sclerosis type, Stage III(X)B based on the biopsy specimen from the right
      subcutaneous lumbodorsal mass.

PMID- 18827424
TI  - A rare case of a tracheal fibroepithelial polyp treated by an endobronchial
      resection.
AB  - This report describes a very rare case of a tracheal fibroepithelial polyp. A 69
      year-old male had been treated in this department because of chronic obstructive
      pulmonary disease since 2006. In July 2007, chest computed tomography revealed a
      bronchial tumor located at the distal end of the trachea. A bronchoscopic
      examination revealed a multilocular polyp. An endobronchial resection was
      performed to remove the lesion. A tracheobronchial fibroepithelial polyp is very
      rare. We herein describe and discuss the appropriate therapeutic policy and also
      review the pertinent literature.

PMID- 18827425
TI  - Mycobacterium avium pleuritis in a non-immunocompromised patient.
AB  - Nontuberculous mycobacterium infection is rarely accompanied by pleural
      involvement. We describe a very rare occurrence of Mycobacterium (M) avium
      pleuritis with pleural effusion in a non-compromised 73-year-old woman patient
      who had been treated for sick sinus syndrome. She was admitted to our hospital
      with general malaise and left pleural effusion. To establish a definitive
      diagnosis, a biopsy specimen was obtained from the left parietal pleura by video
      assisted thoracoscopic surgery. The pleural biopsy specimen revealed only diffuse
      lymphoid cell infiltration and neoplastic or granulomatous lesions were absent.
      Culture of the pleural biopsy specimen revealed M. avium, indicating that the
      pleuritis was caused by this organism. A course of anti-tubercular agents
      (rifampin, ethambutol and streptomycin sulfate) and clarithromycin gradually
      resolved the pleural effusion.

PMID- 18827426
TI  - Recurrence of hepatitis-associated aplastic anemia after a 10-year interval.
AB  - Hepatitis-associated aplastic anemia (HAA) has been reported to show a successful
      outcome following immunosuppressive treatment. On the other hand, the long-term
      prognosis of HAA has not been sufficiently clarified. Herein we report a patient
      with HAA who had been treated with cyclosporine for one year, and maintained
      complete remission without treatment. Ten years later, acute non-A, non-B, and
      non-C hepatitis reccurred followed by bone marrow aplasia. A second
      immunosuppressive treatment with antithymocyte globulin and cyclosporine was
      effective. This case might provide useful information for the long-term follow-up
      of patients with HAA.

PMID- 18827427
TI  - Chronic myeloid leukemia following chemotherapy with 5'-deoxy-5-fluorouridine for
      gastric cancer.
AB  - We report here a very rare case of chronic myeloid leukemia (CML) following long
      term chemotherapy with 5'-deoxy-5-fluorouridine (5'-DFUR) for gastric cancer. A
      69-year-old man was diagnosed with the chronic phase of CML. Six years
      previously, he underwent radical subtotal gastrectomy for gastric cancer, and was
      subsequently treated with oral anti-metabolite 5'-DFUR as adjuvant chemotherapy
      for 6 years. He was placed on imatinib therapy, and achieved a major molecular
      response 10 months after the initiation of therapy. This is the first reported
      case of therapy-related CML following 5'-DFUR treatment.

PMID- 18827428
TI  - Reversible respiratory failure due to rhabdomyolysis associated with
      cytomegalovirus infection.
AB  - A 58-year-old woman presented with muscle weakness, whole body myalgia, and
      dyspnea. On admission, neurological examination showed proximal muscle weakness
      in the extremities. The weakness gradually extended to the bulbar and respiratory
      muscles, necessitating an artificial ventilator. Serum CK level was markedly
      increased (33,774 IU/L; normal <150 IU/L) and myoglobinuria was noted in
      urinalysis. There was no sign of renal failure. Nerve conduction study was
      normal, but needle EMG showed myopathic changes in the weak muscles. Serological
      studies for virus titers showed more than a four-fold increase of cytomegalovirus
      (CMV) antibody titer during the disease course. The IgM anti-GM2 antibody was
      also elevated in the acute phase and decreased in the recovery phase. The muscle
      weakness and respiratory failure gradually improved after intravenous
      methylprednisolone administration, and the serum CK level was normalized in
      several days. CMV infection was thought to have played a central role in the
      rhabdomyolysis, leading to critical but reversible respiratory muscle paralysis.

PMID- 18827429
TI  - Non-caseous granulation lymphadenitis in the neck as an initial manifestation of
      prostate carcinoma.
AB  - We encountered a 54-year-old Japanese man who presented with painless swellings
      on his bilateral neck. Although ultrasonographic findings suggested metastatic
      lymphadenopathy, histological examination of the mass revealed non-caseous
      granulation lymphadenitis. He was subsequently diagnosed as having prostate
      carcinoma with metastasis to the multiple bones. The present case suggested that
      prostate carcinoma could cause cervical lymphadenopathy due to non-caseous
      granulation as an initial manifestation, and could be a sign for an impending
      clinical expression of metastasis to an area draining to the lymph nodes.

PMID- 18827430
TI  - Mercedes-Benz mark sign in the aorta.

PMID- 18827431
TI  - A giant FSH-producing pituitary adenoma protruding into the lateral ventricles.

PMID- 18827432
TI  - Tuberculous Addison's disease mimics malignancy in FDG-PET images.

PMID- 18827433
TI  - Lung cancer presenting as an asymptomatic pneumatocele.

PMID- 18827434
TI  - Optic neuritis caused by interferon-beta administration.

PMID- 18827435
TI  - Compressive retrobulbar optic neuropathy due to hypertrophic pachymeningitis.

PMID- 18827436
TI  - Effectiveness of leukocytapheresis for refractory foot ulceration in rheumatoid
      arthritis.

PMID- 18827437
TI  - Pleural cryptococcosis with idiopathic CD4 positive T-lymphocytopenia.

PMID- 18827438
TI  - Melatonin reduces oxidative stress induced by chronic exposure of microwave
      radiation from mobile phones in rat brain.
AB  - PURPOSE: The aim of the study was to evaluate the intensity of oxidative stress
      in the brain of animals chronically exposed to mobile phones and potential
      protective effects of melatonin in reducing oxidative stress and brain injury.
      MATERIALS AND METHODS: Experiments were performed on Wistar rats exposed to
      microwave radiation during 20, 40 and 60 days. Four groups were formed: I group
      (control)- animals treated by saline, intraperitoneally (i.p.) applied daily
      during follow up, II group (Mel)- rats treated daily with melatonin (2 mg kg(-1)
      body weight i.p.), III group (MWs)- microwave exposed rats, IV group (MWs + Mel)-
      MWs exposed rats treated with melatonin (2 mg kg(-1) body weight i.p.). The
      microwave radiation was produced by a mobile test phone (SAR = 0.043-0.135 W/kg).
      RESULTS: A significant increase in the brain tissue malondialdehyde (MDA) and
      carbonyl group concentration was registered during exposure. Decreased activity
      of catalase (CAT) and increased activity of xanthine oxidase (XO) remained after
      40 and 60 days of exposure to mobile phones. Melatonin treatment significantly
      prevented the increase in the MDA content and XO activity in the brain tissue
      after 40 days of exposure while it was unable to prevent the decrease of CAT
      activity and increase of carbonyl group contents. CONCLUSION: We demonstrated two
      important findings; that mobile phones caused oxidative damage biochemically by
      increasing the levels of MDA, carbonyl groups, XO activity and decreasing CAT
      activity; and that treatment with the melatonin significantly prevented oxidative
      damage in the brain.

PMID- 18827439
TI  - Low-dose effects of bisphenol A: a serious threat to human health?
AB  - The author tried to review and summarize low-dose effects of endocrine disrupting
      chemicals (EDCs) through an extensive literature survey of toxicological studies
      with bisphenol A (BPA), taking BPA as an example for which many studies were
      published. Data on low-dose effects with BPA, especially on neurobehavioral
      effects after fetal or early postnatal exposures, suggested that there would be
      new aspects to be considered. Specific mention for future tasks was made.
      Firstly, toxicity tests should be designed with more elaboration to ensure a
      sufficient number of animals with careful handling of litters to allow adequate
      statistical analysis and appropriate selection of dosages to obtain insight in
      dose-response relationship. Secondly, precise measurement of plasma levels in
      both humans and rodents and construction of relevant physiologically-based
      pharmacokinetic models would help obtain quantitative estimates of intake and
      target-organ exposure relationship. Thirdly, biological backgrounds, particularly
      differences and similarities in endocrinological, neurological and immunological
      aspects among species, should be revisited. Fourthly, mechanistic deliberations
      on the possibilities of epigenetic mechanism and examinations of putative
      neurobehavioral effects or a presumptive link of miscarriage with BPA exposures
      are requested. Finally, general public concerns must be addressed in a thoughtful
      way so that a simple precautionary approach is not pursued, but uncertainties of
      the new toxicological aspects should be carefully explained. Further researches
      and internationally concerted efforts on elucidating risk of low-dose effects by
      integrating knowledge will contribute to setting new directions in toxicology and
      improving chemical risk assessments.

PMID- 18827440
TI  - Regulation of insulin-like growth factor binding protein-1 and lipoprotein lipase
      by the aryl hydrocarbon receptor.
AB  - The aryl hydrocarbon receptor (Ahr), a ligand-activated transcriptional factor,
      mediates the transcriptional activation of a battery of genes encoding drug
      metabolism enzymes. In the present study, we investigated the hepatic mRNA
      expression profile in Ahr-null (Ahr KO) mice compared to wild-type mice by
      microarray analysis to find new Ahr target genes. Pooled total RNA samples of
      liver extracted from 7- and 60-week-old Ahr KO or wild-type mice were studied by
      DNA microarray representing 19,867 genes. It was demonstrated that 23 genes were
      up-regulated and 20 genes were down-regulated over 2 fold in Ahr KO mice compared
      with wild-type mice commonly within the different age groups. We focused on
      insulin-like growth factor binding protein-1 (Igfbp-1) and lipoprotein lipase
      (Lpl) that were up-regulated in Ahr KO mice. The higher expression in Ahr KO mice
      compared to wild-type mice were confirmed by real-time RT-PCR analysis. In the
      wild-type mice but not in the Ahr KO mice, 2,3,7,8-tetrachlorodibenzo-p-dioxin
      (TCDD) treatment increased the Igfbp-1 and Lpl mRNA levels. The expression
      profile of Igfbp-1 protein was consistent with that of Igfbp-1 mRNA. Since Lpl is
      the primary enzyme responsible for hydrolysis of lipids in lipoproteins, the
      serum triglyceride levels were determined. Indeed, the serum triglyceride levels
      in Ahr KO mice was lower than that in wild-type mice in accordance with the Lpl
      mRNA levels. Contrary to our expectation, TCDD treatment significantly increased
      the serum triglyceride levels in wild-type, but did not in Ahr KO mice. These
      results suggest that serum triglyceride levels are not correlated with hepatic
      Lpl expression levels. In the present study, we found that Ahr paradoxically
      regulates Igfbp-1 and Lpl expressions in the liver.

PMID- 18827441
TI  - Evaluation of trace metals in tobacco of local and imported cigarette brands used
      in Pakistan by spectrophotometer through microwave digestion.
AB  - Uncontrolled exposure of active and passive smokers to trace metals causes
      increase in health risks. The primary objective of this study was to determine
      whether local and imported cigarette brands used in Pakistan, have elevated
      levels of metals or not. Six metals manganese (Mn), cobalt (Co), copper (Cu),
      cadmium (Cd), lead (Pb) and zinc (Zn) were determined in tobacco of twenty
      cigarette brands (local and imported) used in Pakistan by flame atomic absorption
      Spectrophotometry. To overcome contamination chances and for complete digestion
      of analytes a microwave digester was used. The analytical results showed highest
      concentration of Mn (84.78 microg/g dry weight), Cd (0.525 microg/g dry weight)
      and Zn (14.34 microg/g dry weight) metals in imported brands in relation to
      counterparts from the local brands. Certain elevated levels were observed for Co
      (3.344 microg/g dry weight), Pb (14.16 microg/g dry weight) and Cu (7.889
      microg/g dry weight) metals in local brands. The inter-metal relationships in the
      tobacco of local and imported cigarette brands showed some integrated variation
      in the selected metal levels. In view of health risk associated with the above
      metals, there should be a strict quality control over monitoring of heavy metals
      during growing, processing and smoking of tobacco. Therefore, it is prudent to
      minimize exposure to toxic substances whenever possible because smoking and
      exposure to cigarette smoke is a confounder to be taken into account when
      carrying out epidemiological studies on human exposure to metals.

PMID- 18827442
TI  - Effect of glutathione (GSH) depletion on DNA damage and blood chemistry in aged
      and young rats.
AB  - DNA is damaged by reactive oxygen species (ROS) and such damage is age-dependent.
      Blood chemical parameters also change age-dependently. Glutathione (GSH) plays an
      important role as an antioxidant. However, the effects of GSH on DNA damage and
      blood chemistry are unclear. Therefore, this study was aimed to evaluate GSH
      contribution to DNA damage and changes of blood chemical parameters in aged and
      young rats. The GSH content in the livers and kidneys of aged rats (20 months)
      were lower than that in young rats (9 weeks of age) with higher DNA damage
      detected by a comet assay. There was a negative correlation between the GSH
      content and the DNA damage in the liver and kidney. L-buthionine (S,R)
      sulfoximine (BSO; 0, 5, 20 mM), which inhibits GSH synthesis, was administered in
      drinking water for 28 days to young and aged rats (8 weeks and 19 months of age
      at the start of the administration). The treatment significantly decreased GSH
      levels in the heart, liver, lung and kidney of either the young or aged rats
      without causing DNA damage in those organs. When compared with young rats, aged
      rats showed higher levels in aspartate aminotransferase, alanine
      aminotransferase, total bilirubin, total cholesterol, globulin, creatinine,
      sodium and chloride and lower levels in alkaline phosphatase, triglyceride,
      albumin/globulin and inorganic phosphorus. However, BSO did not change these
      parameters in young or aged rats. These results showed that there was a negative
      correlation between GSH and DNA damage during aging, but the BSO-induced GSH
      depletion did not affect DNA damage or blood chemistry levels in young and aged
      rats under these study conditions.

PMID- 18827443
TI  - Screening of toxicological properties of 4-methylbenzoic acid by oral
      administration to rats.
AB  - Oral toxicity of 4-methylbenzoic acid in male and female Sprague-Dawley rats was
      profiled through a twenty-eight-day repeated dose toxicity study (the 28-day
      study) and a screening test for reproductive/developmental toxicities (the
      reproduction/developmental study) conducted under Organisation for Economic Co
      operation and Development (OECD) test guidelines. Daily administration of 4
      methylbenzoic acid, at a dose level of 0, 100, 300 or 1,000 mg/kg, did not show
      any adverse effect on reproductive organs of animals in the 28-day study. In the
      reproductive/developmental study, however, 1,000 mg/kg/day of the compound
      reduced epididymal weights and increased incidence of cauda epididymal
      oligo/azoospermia. While the compound did not affect estrous cycle or mating
      performances, 1,000 mg/kg of the compound reduced fertility. Furthermore, 300
      mg/kg or more of the compound increased pre-implantation loss, which resulted in
      a decrease in the number of offspring, and reduced body weight gain of the dams
      during the latter period of gestation. From these results, the no-observed-effect
      level (NOEL) for reproductive/developmental toxicities is considered to be 100
      mg/kg, whereas 1,000 mg/kg did not show any effect on neonates. In the 28-day
      study, NOEL is considered to be 300 mg/kg for male and female rats, since 1,000
      mg/kg of the compound caused, in both sexes, a few minor changes, such as
      temporal salivation, a slight increase in food consumption and a moderate
      increase in blood aspartate aminotransferase (AST) activity. Thus, 4
      methylbenzoic acid has the potential for reproductive toxicity, with diverse
      adverse effects on the epididymis, after repeated administration, observed in the
      two studies.

PMID- 18827444
TI  - Strain differences in hepatic cytochrome P450 1A and 3A expression between
      Sprague-Dawley and Wistar rats.
AB  - Expression of hepatic cytochrome P450 (CYP) isoforms was compared in Sprague
      Dawley (SD) and Wistar (WI) rats, which are commonly used strains in preclinical
      studies. Basal CYP1A1, CYP1A2, and CYP3A2 mRNA levels were higher in WI rats than
      in SD rats (by 8-, 3- and 2-fold, respectively). Treatment with phenobarbital, a
      potent CYP inducer, increased the predominance of expression of these three mRNAs
      in WI rats (by 26-, 4-, and 2-fold, respectively) along with the predominance of
      increased microsomal total P450 contents and smooth-surface endoplasmic reticulum
      in the centrilobular hepatocytes. CYP1A enzymatic activity was also higher in WI
      rats than in SD rats. No strain differences were observed in phenobarbital
      induction of CYP2B1/2, CYP2C6, or CYP3A1. CYP3A2 mRNA was more strongly induced
      by dexamethasone, a typical inducer of CYP3A, together with CYP3A1 mRNA, in WI
      rats than in SD rats (by 2-fold), whereas the CYP1A1 and CYP1A2 mRNA expression
      induced by beta-naphtoflavone, a typical inducer of CYP1A, did not differ between
      the two strains. Furthermore, WI rats exhibited predominantly arylhydrocarbon
      receptor, pregnane X receptor, and constitutive androstane receptor mRNAs,
      responsible for CYP1A or CYP3A induction, with phenobarbital or dexamethasone
      induction. In conclusion, significant, predominant expression of hepatic CYP1A
      and CYP3A mRNAs in WI rats was observed, possibly related to nuclear receptor
      mediated induction. Considering the pharmacokinetic and toxicological importance
      of CYP1A and CYP3A, different outcomes might arise depending on the rat strains
      used in preclinical studies of drugs metabolized typically or mainly by both
      isoforms.

PMID- 18827445
TI  - Prevention of incipient diabetic cardiomyopathy by high-dose thiamine.
AB  - Diabetic cardiomyopathy can progress toward overt heart failure with increased
      mortality. The hexosamine biosynthesis pathway has been implicated in signaling
      for fibrosis by the kidney. Thiamine (vitamin B(1)) is an indispensable coenzyme
      and required at intracellular glucose metabolism. In this study, we assessed if
      decrease of flux through the hexosamine biosynthesis pathway induced by high-dose
      thiamine therapy counteracts diabetes-induced cardiac fibrosis. The diabetes
      model used was the streptozotocin-induced diabetic rat. Normal control and
      diabetic rats were studied for 2 weeks with and without thiamine, and followings
      were analyzed; plasma biochemicals (total cholesterol and triglycerides),
      morphological changes, mRNA abundance relevant to cardiac failure (brain
      natriuretic peptide) and fibrosis (transforming growth factor-beta1,
      thrombospondine, fibronectin, plasminogen activator-I and connective tissue
      growth factor) as well as and matrix metalloproteinase activity were
      investigated. Thiamine repletion prevented diabetes-induced cardiac fibrosis
      without changes in plasma glucose concentration. This was achieved by prevention
      of thiamine depletion, increased pro-fibrotic mRNA abundance and decreased
      metalloproteinase activity in the heart of diabetic rats. O-glycosylated protein
      was significantly higher in the left ventricular of diabetic rats compared to
      control rats, which was decreased by thiamine administration. Thiamine repletion
      prevented diabetes-induced cardiac fibrosis in experimental diabetes, probably by
      suppression of hexosamine biosynthesis pathway.

PMID- 18827446
TI  - Expression of sonic hedgehog regulates morphological changes of rat developing
      cerebellum in hypothyroidism.
AB  - Although thyroid hormones are crucial for cerebellar development, and several
      thyroid hormone-dependent genes are known to be correlated with morphological
      development of the cerebellum, the precise mechanisms of morphological cerebellar
      changes in hypothyroidism (HT) remain unknown. To investigate these mechanisms in
      experimental rat HT induced by the anti-thyroid drug methimazole (MMI-HT rat), we
      carried out gene expression analysis (sonic hedgehog (Shh), reelin, and Bax)
      using quantitative real-time PCR. Histological examination revealed cerebellar
      abnormalities, including reductions in the thickness of the molecular layer and
      delayed disappearance of the external granular layer (EGL), as well as excess
      bulges or sublobules in the internal granular layer (IGL). At Postnatal Day (P)
      6, Shh expression in MMI-HT rat was comparable to that in controls, thus
      suggesting that Shh expression was sufficient to form the lobes in the initial
      phase. However, Shh expression decreased in the later phases, as compared with
      age-matched controls. This demonstrated that stronger and sustained signaling is
      necessary for partitioning of the cardinal lobes into lobes and sublobes.
      Although reelin expression was not clearly different from that in controls, Bax
      expression decreased at P 15. The attrition of Bax at P 15 as well as Shh in the
      later phase may be related to irregularities in the IGL and the relatively large
      numbers of internal granular cells. Taken together, these results suggest that
      Shh expression is related to the morphological cerebellar changes in experimental
      hypothyroidism and that sustained signaling by Shh may play a key role in normal
      development, particularly lobulation, in the cerebellum.

PMID- 18827447
TI  - Protective role of metallothionein in bone marrow injury caused by X-irradiation.
AB  - In order to elucidate the role of metallothionein (MT) in preventing the adverse
      effects of X-ray irradiation, we examined the susceptibility of MT-I/II null mice
      to bone marrow injury caused by X-irradiation and effects of pretreatment with MT
      inducing metals on X-ray injury. Eight-week-old male mice were exposed to a
      single bout of whole-body X-irradiation at a dose between 0.1 and 6.0 Gy. The
      numbers of leukocytes, reticulocytes with micronuclei (MNRET) in the blood, and
      polychromatic erythrocytes with micronuclei (MNPCE) in the bone marrow were
      determined 24 hr after X-irradiation. X-irradiation significantly decreased the
      total number of leukocytes in MT-I/II null mice and wild-type mice in a dose
      dependent manner, but the total number of leukocytes was significantly lower in
      MT-I/II null mice than in wild-type mice at a low dose of irradiation, between
      0.1 and 1.0 Gy. X-irradiation (0.1 and 0.5 Gy) significantly increased the
      appearance of MNRET and MNPCE in both strains, but the increase was greater in
      the MT-I/II null mice than in the wild-type mice. Additional groups of mice were
      pre-administered bismuth nitrate or zinc sulfate to induce MT in the bone marrow
      cells prior to X-irradiation; the X-ray injury was prevented by such treatments
      in wild-type mice only. Thus, the present results suggest that MT plays a
      protective role against a low dose of X-ray injury.

PMID- 18827448
TI  - Chinese dumpling scare hits Japan--a case of methamidophos food poisoning.
AB  - An outbreak of food poisoning that affected at least ten people in various
      regions of Japan was traced to exposure to Chinese dumplings contaminated with
      the organophosphate insecticide Methamidophos. We experienced the most serious
      case, a five years old girl, who suffered coma. She presented with features of
      cholinergic overactivity and her serum cholinesterase activity was 9 U/l. We
      started intravenous treatment with pralidoxime iodide, atropine sulfate, and
      midazolam. Her symptoms improved gradually and she was discharged on day 25
      without any sequelae. Though poisoning attributed to organophosphate insecticides
      has become less common in recent years, it is even more important to diagnose the
      problem rapidly based on the characteristic symptoms and to start specific
      treatment at the earliest possible stage after poisoning.

PMID- 18827449
TI  - Arsenite but not arsenate inhibits general proteoglycan synthesis in cultured
      arterial smooth muscle cells.
AB  - Epidemiological and experimental studies have suggested that exposure to
      metalloid arsenic constitutes a risk factor for vascular disease associated with
      atherosclerosis. Since in atherosclerosis, types of proteoglycans (PGs) present
      change depending on the stage, we investigated the effect of 2 chemical forms of
      inorganic arsenic-a trivalent sodium arsenite and a pentavalent sodium arsenate
      on the synthesis of PGs in cultured arterial smooth muscle cells. The results
      indicate that arsenite but not arsenate, at a noncytotoxic level, inhibits
      general PG synthesis independent of cell density. Arsenite may be one of the
      chemical forms of inorganic arsenic that influences the PG composition in blood
      vessel walls during the progression of vascular disorders such as
      atherosclerosis.

PMID- 18827450
TI  - Carcinogenic comparative study on rasH2 mice produced by two breeding facilities.
AB  - CByB6F1-Tg(HRAS)2Jic mice (brand name: rasH2 mouse) are produced by two breeding
      facilities, CLEA Japan, Inc. (Fuji, Shizuoka, Japan) and Taconic (Germantown, NY,
      USA), and supplied world wide. To confirm carcinogenic conformity of both mice, a
      26-week carcinogenicity test was performed on a total of 120 mice obtained from
      both facilities under the same protocol and same timing in our facility. All mice
      were divided into a vehicle (citrate buffer at pH 4.5, 10 ml/kg, single
      intraperitoneal injection) group and a MNU (N-methyl-N-nitrosourea, 75 mg/kg,
      single intraperitoneal injection) group. Fifteen mice of each sex were assigned
      to each group. The survival rate of the vehicle group was maintained at 100% for
      mice from both facilities at completion of the test. In the MNU group, MNU
      induced tumor death occurred from 9 to 12 weeks after administration, and the
      final survival rate for both facilities was 6.7%. In the pathological
      examination, only benign tumors of lungs, spleen, forestomach and skin were
      observed in a few mice in the vehicle group of both facilities. In the MNU group,
      the incidence of forestomach papilloma/squamous cell carcinoma in mice from both
      facilities was 100%. The incidences of malignant lymphoma in CLEA Japan mice and
      Taconic mice were 86.7% and 93.3%, respectively, and no significant difference
      was observed (Fisher's exact probability test). Although lung adenoma and skin
      papilloma/keratoacanthoma, which are major MNU induced tumors in this strain,
      were observed in several mice from both facilities, no significant differences
      were found. Consequently, carcinogenic conformity of rasH2 mice derived from two
      breeding facilities was confirmed by the present study.

PMID- 18827451
TI  - Comparative study of histamine H4 receptor expression in human dermal
      fibroblasts.
AB  - The histamine H4 receptor (H4R) is the newest receptor identified of four
      histamine receptors. Its expression in numerous immune and inflammatory organs
      has been implicated in relation to immune systems and allergic diseases. In the
      present study, we demonstrate the expression of H4R in human dermal fibroblasts
      and investigate changes in its expression level when stimulated by histamine,
      phorbol 12-myristate 13-acetate (PMA), lipopolysaccharides (LPS), dexamethasone
      and indomethacin. Histamine and PMA showed no effects on H4R expression. LPS and
      indomethacin up-regulated H4R mRNA expression, and 20 microM dexamethasone
      increased H4R protein levels. These results indicate a good prospective for this
      new receptor in the development of effective treatments of inflammatory diseases
      and pruritus or for the appropriate prevention of toxicities.

PMID- 18827452
TI  - Unexpected sudden deaths of F344 rats in long-term toxicity studies: relationship
      between sudden deaths and stomach tube material or feed type.
AB  - Sudden deaths of F344 rats (F344/Du Crj (Fischer)) have occurred frequently in
      the late stage of carcinogenicity studies using stomach tubes. To reduce the
      sudden deaths, the incidence of sudden deaths was compared in the control groups
      from 104-week carcinogenicity studies using two different stomach tubes (metal
      and Teflon) and feeds (pellet and powder). The results indicate that replacing
      metal tubes with Teflon tubes from the first administration or after week 41 of
      administration was not effective in reducing the sudden deaths. On the other
      hand, sudden deaths did not occur at all after changing the feed from pellets to
      powder after week 44 or 79 of administration. In addition, although decreased
      body weight and retention of feed in the oral, pharyngeal and laryngeal cavities
      were observed in the animals that died suddenly, there were no abnormalities in
      histopathological examination. Therefore, it is suggested that changing the feed
      from pellets to powder should be effective in reducing the sudden deaths of F344
      rats in long-term oral gavage studies or carcinogenicity studies.

PMID- 18827453
TI  - Correlation between high field MR images and histopathological findings of rat
      transplanted cancer immediately after partial microwave coagulation.
AB  - PURPOSE: To investigate the immediate effects of microwave coagulation on rat
      tumors in various magnetic resonance (MR) images at high magnetic field strength
      using histopathological examinations as reference. MATERIALS AND METHODS: Tumors
      implanted in rat femurs were partially thermocoagulated by microwave. Immediately
      after, T1- and T2-weighted images, diffusion-weighted images (DWIs), and contrast
      enhanced T1 weighted images (CE-T1WIs) were acquired with a 7-tesla MR scanner.
      After measurements, tumors were examined histopathologically with hematoxylin
      eosin (HE) staining and histochemically for acid phosphatase activity. RESULTS:
      Without contrast, boundaries of coagulated areas were unclear on MR images,
      including apparent diffusion coefficient (ADC) maps. CE-T1WIs clearly showed
      immediate contrast enhancement of untreated areas of tumor, and the area of
      enhancement gradually enlarged in 5 min. Quantitative analyses were conducted by
      classifying tumor areas by contrast enhancement results. Signal intensities of
      the areas in the MR images showed no significant differences, but at the
      periphery, ADC values were significantly higher in areas with delayed enhancement
      than those with immediate enhancement. Compared with histopathological findings,
      with microwave thermocoagulation, increased ADC value seemed to derive from
      collection of extracellular fluid in the outer zone, where acid phosphatase
      activity was attenuated. CONCLUSION: ADC values in the areas with delayed
      enhancement of CE-T1WIs were higher than those in non-affected areas, but MR
      images could not show areas of coagulation within tumors. Clear detection of the
      boundaries of coagulated areas required contrast enhancement, even at magnetic
      field strength of 7T.

PMID- 18827454
TI  - Development of a noninvasive method to measure intravascular and intracardiac
      pressure differences using magnetic resonance imaging.
AB  - PURPOSE: We developed a noninvasive method using magnetic resonance (MR) imaging
      to measure differences in intravascular and intracardiac pressure, and we
      investigated the feasibility of the method's use in a pulsatile flow phantom and
      human studies. METHODS: We measured 3 velocity components using phase contrast MR
      imaging on a 1.5T MR scanner, used velocity data in Navier-Stokes equations to
      obtain pressure gradients, and directly integrated the in-plane pressure
      gradients to calculate pressure differences. To validate our method, we compared
      the pressure differences obtained by our method with the theoretical values
      obtained from an axisymmetric model of arterial stenosis. We also estimated the
      pressure differences in glass-tube phantoms simulating various vascular
      pathologies and in the left ventricle and aortic arch of a normal volunteer as
      clinical application. RESULTS: The pressure differences obtained by our method
      agreed well with theoretical values obtained using the straight-tube phantom with
      stenosis of 45%, but we observed some differences when stenosis was 65%. We
      clearly observed variations in pressure differences at specific locations at
      various phases of a cardiac cycle in both phantom and human studies. CONCLUSION:
      This method appears useful for measuring intravascular and intracardiac pressure
      differences.

PMID- 18827455
TI  - Detection of hepatocellular carcinoma with ferucarbotran (resovist)-enhanced
      breath-hold MR imaging: feasibility of 10 minute-delayed images.
AB  - PURPOSE: We evaluated the optimal timing for breath-hold MR imaging with bolus
      injectable superparamagnetic iron oxide (SPIO) for detecting hepatocellular
      carcinoma (HCC). MATERIALS AND METHODS: Twenty patients with 62 HCCs (52
      hypervascular, 10 non-hypervascular) underwent MR imaging that included
      unenhanced and SPIO-enhanced T1-weighted gradient echo (GRE) and T2-weighted fast
      spin echo (FSE) sequences, perfusion study, and SPIO-enhanced T2*-weighted GRE
      sequences. We obtained SPIO-enhanced T2*-weighted sequences 10 and 30 min after
      injecting SPIO and made 2 image sets, comprising 10- or 30-min delayed T2*
      weighted images. Three observers performed alternative free response receiver
      operating characteristic (AFROC) analysis, and quantitative evaluation was
      performed. RESULTS: Only Observers 2 and 3 recognized a significant difference in
      the area under the AFROC curve (Az) value in the 10-min delayed images; no
      significant difference was observed in the 30-min delayed images. There was no
      significant difference in the sensitivity of individual observers between 10- and
      30-min delayed images. The contrast-to-noise (C/N) ratio of the 30-min delayed
      images was significantly higher than that of the 10-min delayed images. The C/N
      ratio of hypervascular HCCs in the 30-min delayed images was significantly higher
      than in the 10-min delayed images, but that of non-hypervascular HCCs showed no
      significant difference. CONCLUSION: In most cases, 10-min delayed SPIO-enhanced
      T2*-weighted images are sufficient to detect HCCs.

PMID- 18827456
TI  - Production of a human-tissue-equivalent MRI phantom: optimization of material
      heating.
AB  - PURPOSE: We conceived a 2-stage heating method to dissolve the ingredients of
      magnetic resonance (MR) imaging phantoms to overcome issues of uneven quality in
      conventional MR imaging phantoms, and we evaluated uniformity and the
      reproducibility of our method. METHODS: We used a 3-liter capacity, column
      shaped, enamel-coated porcelain container to produce a muscle-equivalent phantom
      (diameter, 160 mm; height, 100 mm; volume, 2 liters). The phantom contained: 1)
      carrageenan as a gelling agent; 2) agarose as a T2 modifier; 3) GdCl3 as a T1
      modifier; 4) NaN3 as an antiseptic; and 5) distilled water. We applied both
      direct heating and 2-stage heating of pre-soaked materials. We placed powdered
      materials directly into hot water for direct heating but soaked them in water one
      day before use (post-swelling) in 2-stage heating. The materials in the container
      were melted in a silicone oil bath of 120 or 140 degrees C under various
      conditions, then allowed to gel by natural cooling. We observed the resulting gel
      phantoms macroscopically using a CCD camera and evaluated their uniformity by
      microscopy and MR imaging. RESULTS: We found it necessary to raise the
      temperature inside the phantom to 100.0 degrees C, to produce a uniform gel with
      stable homogeneity and few bubbles. Use of an enamel-coated porcelain container
      required setting the temperature of the oil bath at 140 degrees C. CONCLUSION: A
      uniform and reproducible human tissue-equivalent phantom with few bubbles can be
      manufactured using our 2-stage heating method, which employs pre-soaking in a
      silicone oil bath at 140 degrees C for 30 min. We then added the swollen
      carrageenan to the agarose solution, which heating the temperature to 140 degrees
      C for 30 min while continuously stirring at 120 rpm, following with natural
      cooling.

PMID- 18827457
TI  - Ontology for FMRI as a biomedical informatics method.
AB  - Ontological engineering is one of the most challenging topics in biomedical
      informatics because of its key role in integrating the heterogeneous database
      used by biomedical information services. Ontology can translate concepts and
      their real-world relationships into expressions that can be processed by computer
      programs or web services, providing a unique taxonomic frame to describe a
      pathway for extracting, processing, storing, and retrieving information. In
      developing clinical functional neuroimaging, which requires the integration of
      heterogeneous information derived from multimodal measurement of the brain, these
      features will be indispensable. Neuroimaging ontology is remarkable in that it
      requires detailed description of the hypothesis, the paradigm employed, and a
      scheme for data generation. Neuroimaging modalities, such as functional magnetic
      resonance imaging (fMRI), magnetoencephalography (MEG), electroencephalography
      (EEG), and near infrared spectroscopy (NIRS), share similar application purposes,
      imaging protocol, analyzing methods, and data structure; semantic gaps that
      remain among the modalities will be bridged as ontology develops. High
      performance, global resource information database (GRID) computing and the
      applications organized as service-oriented computing (SOC) will support the heavy
      processing to integrate the heterogeneous neuroimaging system. We have been
      developing such a distributed intelligent neuroimaging system for real-time fMRI
      analysis, called BAXGRID, and a neuroimaging database. The fMRI ontology of this
      system will be integrated with established medical ontologies, such as the
      Unified Medical Language System (UMLS).

PMID- 18827458
TI  - Fractional anisotropy values of calf muscles in normative state after exercise:
      preliminary results.
AB  - PURPOSE: We measured fractional anisotropy (FA) of calf muscles from diffusion
      tensor (DT) images from simultaneous scanning of bilateral calves and determined
      changes in values after unilateral exercise loading. METHOD: We obtained DT
      images of both calves of 10 healthy male volunteers and measured FA of the
      anterior tibialis, gastrocnemius, and soleus muscles. Two of the ten were
      subjected to loaded exercise in their right calves; we recorded FA values
      immediately after exercise and 24 hours, 72 hours, and 1 week later. RESULTS: At
      rest, the mean FA values of the 20 calves were 0.63+/-0.02 in the anterior
      tibialis, 0.56+/-0.05 in the gastrocnemius, and 0.57+/-0.04 in the soleus
      muscles. The differences were statistically significant (P<0.001) by analysis of
      variance (ANOVA), and differences between anterior tibialis and gastrocnemius
      (corrected P<0.01) and anterior tibialis and soleus (corrected P<0.01) muscles
      were significant by Bonferroni post hoc test. The FA values of the exercise
      loaded soleus and gastrocnemius muscles of the 2 volunteers decreased just after
      exercise but gradually recovered to the baseline after one week. CONCLUSION: Our
      method may be useful for assessing minimal muscle damage related to muscle
      fatigue.

PMID- 18827459
TI  - Diffusion tensor imaging in familial spastic paraplegia with mental impairment
      and thin corpus callosum.
AB  - We investigated 2 Japanese siblings with a complicated form of familial spastic
      paraplegia. Cranial magnetic resonance (MR) imaging revealed marked thinning of
      the corpus callosum. Diffusion tensor imaging (DTI) showed microstructural
      changes in the thalamus, basal ganglia, and cerebral white matter, and single
      photon emission computed tomography (SPECT) using 99mTc-ethylcysteinate dimer
      showed very similar findings. DTI and SPECT effectively revealed global changes
      not revealed by conventional MR imaging.

PMID- 18827460
TI  - [Studies on the constituents of cucurbitaceous plants].
AB  - I have an opportunity to have co-operative studies with Chinese group of Kunming
      Institute of Botany. Since then, I have investigated the chemical constituents of
      a number of Chinese plants of Araliaceae, Umbelliferae, Labiatae, Cucurbitaceae
      and other families. This review describes the structural elucidation of the
      cucurbitane, oleanane and dammarane glycosides, and their biological activities
      under the joint studies on cucurbitaceous plants, Bolbostemma, Hemsleya, Siraitia
      and Neoalsomitra species. New oleanane glycosides having novel cyclic structure
      were isolated from Bolbostemma paniculatum. The potent solubilizing effect of
      these compounds was investigated. A number of cucurbitane glycosides were
      isolated from Hemsleya carnosiflora, H. panacis-scandens, Siraitia grosvenorii
      and S. siamensis. Some of these glycosides taste sweet, bitter or tasteless. The
      structure-taste relationships of the glycosides of a 3-alpha-hydroxy-cucurbit-5
      ene-type triterpene have been discussed. Anti-tumor-promotion effects as well as
      the ecdysteroid agonist and antagonist activities of these cucurbitane glycosides
      were investigated. New dammarane glycosides were isolated from Neoalsomitra
      integrifoliola.

PMID- 18827461
TI  - [Molecular pathology in atherosclerosis: the mechanism by which cholesteryl ester
      accumulates in atheromatous aorta].
AB  - To study how cholesterol accumulates in atheroma, novel monoclonal antibodies
      were developed, using crude homogenate of atheroma as immunogens. 212D monoclonal
      antibody recognizing extra cellular matrix with lipid-laden deposits was selected
      by histochemical staining. The antigen was deduced vitronectin from cDNA library.
      DLH3 monoclonal antibody recognizing oxidized LDL, epitope of which was 5- or 9
      phosphatidylcholine. Significant correlations between oxidized LDL and coronary
      heart disease (CHD) patients were observed from clinical study. 256C monoclonal
      antibody recognizing atheromatous lesions in human aorta was selected. Epitope
      must be PC-cholesterol complex which may involve in foam cell rupture.
      Atherogenesis will be discussed from the aspects of these antibodies. Our working
      hypothesis is required to elucidate the mechanism. Denatured lipoproteins (either
      oxidized lipoprotein or ruptured foam cells) may induce atheroma. Oxidation of
      lipoprotein may be taken place both in foam cells and/or extra cellular matrix,
      and macrophage eliminate these denatured lipoproteins and become foam cells. The
      foam cells are ruptured by either apoptosis or necrosis afterward, and
      hydrophobic fragments of foam cells dispersed in extra cellular space, which
      destroys the function of biological membrane. Since biological function could be
      maintained by segregation of hydrophilic circumstances, macrophages uptake these
      fragmented material and oxidized lipoprotein to maintain the function. This
      vicious spiral may enhance chronically the atheroma.

PMID- 18827462
TI  - [Medicinal chemistry targeting nucleosides and nucleic acids based on fine
      synthetic chemistry].
AB  - Nucleosides and nucleotides are one of the most important elements for cells by
      the fact that they are components of DNAs and RNAs. In addition, they play
      important roles in most fundamental cellular metabolic pathways such as energy
      donors, second messengers, and cofactors for various enzymes. Therefore, there
      exists a rich source in drug discovery targeting nucleosides and nucleotides. In
      order to utilize nucleosides and nucleic acids on the drug development, it is
      very important to develop reactions and methods, by which the highly coordinating
      and labile nucleoside intermediates can be used. With these in mind, we have been
      working on synthetic nucleoside and nucleic acid chemistry. First, branched sugar
      nucleoside derivatives, which are potential antitumor agents, have been
      synthesized utilizing samarium diiodide (SmI(2)) mediated Reformatsky reaction or
      aldol reaction. 3'-beta-Carbamoylmethylcytidine (CAMC) was found to exhibit
      potent cytotoxicity against various human tumor cell lines. Synthetic methodology
      of the caprazamycins, which are promising antibacterial nucleoside natural
      products, was also developed by the strategy including beta-selective
      ribosylation without using a neighboring group participation. Our synthetic route
      provided a range of key analogues with partial structures to define the
      pharmacophore. Simplification of the caprazamycins was further pursued to develop
      diketopiperazine analogs. Medicinal chemistry of oligodeoxynucleotides has been
      conducted. Thus, novel triazole-linked dumbbell oligodeoxynucleotides and modular
      bent oligodeoxynucleotides were synthesized. They exhibit excellent binding
      affinity to NF-kappaB or HMGB1 A-box protein, which are important therapeutic
      targets. Therefore, the results obtained conclusively demonstrated these
      oligodeoxynucleotides could be proposed as powerful decoy molecules.

PMID- 18827463
TI  - [Thermodynamically controlled deracemization utilizing inclusion complexation].
AB  - Utilizing host-guest inclusion complexation in the solid state, alpha
      monosubstituted ketones were deracemized using optically active host compounds
      such as (-)-trans-2,3-bis(hydroxydiphenylmethyl)-1,4-dioxaspiro[5.4]decene (1a)
      under alkali conditions. This new method afforded optically active alpha
      monosubstituted ketones in excellent yields with high enantiomeric excesses. For
      example, (+/-)-2-benzylcyclohexanone (2a) and (+/-)-3-benzylhexan-2-one (3c) were
      converted to the R-isomer (74% ee) and the S-isomer (96% ee), respectively, in
      quantitative yields. An x-ray crystallographic study elucidated the structure of
      the inclusion complex of 1a and (R)-2a. The study showed that the host molecules
      1a ingeniously includes the guest molecule (R)-2a via hydrogen bonding and van
      der Waals interactions. As an application of deracemization, coenzyme (R)-alpha
      lipoic acid and (R)-(-)-epilachnene, the antipode of an defensive droplets from
      the Mexican bean beetle, Epilachna varivestis, were synthesized in short steps
      with>99% ee and 87% ee, respectively.

PMID- 18827464
TI  - [Methylglyoxal-induced apoptosis of endothelial cells].
AB  - Diabetic patients exhibit increased blood plasma levels of methylglyoxal (MG), a
      metabolite of glucose. Since MG generates advanced glycation end-products (AGEs)
      that disrupt the functions of such biomolecules as proteins, it is responsible
      for the progression and complications of diabetes. A functional disorder of the
      vascular endothelium may also contribute to the progression and complications of
      diabetes. In endothelial cells, MG is the major precursor for the formation of
      AGEs. In this study, we examined the effects of MG on vascular endothelial cells
      and found that it induced the apoptosis of bovine aortic endothelial cells
      (BAECs). MG induced the collapse of mitochondrial membrane potential, an index of
      apoptosis, and the elevation of caspase-3 activity, an apoptotic execution
      enzyme, leading to cell death. Flow cytometric analyses with annexin-V and
      propidium iodide double staining revealed that cells exposed to a lethal dose of
      MG displayed features characteristic of apoptosis. MG induced an increase in the
      level of intracellular reactive oxygen species (ROS) prior to induction of
      apoptosis. Taken together, these findings suggest that BAECs exposed to MG die by
      apoptosis due to the increase of intracellular ROS level.

PMID- 18827465
TI  - [Comparison of dissolution profile and plasma concentration-time profile of the
      thalidomide formulations made by Japanese, Mexican and British companies].
AB  - Thalidomide is an important advance in the treatment of multiple myeloma. In
      Japan thalidomide is now on the approval step for the treatment of multiple
      myeloma. The drug has some bothersome side effects such as defect of
      organogenesis, neuropathy, constipation and fatigue, but is likely more effective
      than standard chemotherapy and is changing multiple myeloma treatment. At this
      moment, Japanese patients must import the thalidomide preparations from Mexico,
      Britain and elsewhere, but after approval, they patients will be able to get the
      new Japanese thalidomide capsules. In order to determine appropriate amounts of
      Japanese thalidomide capsules in the treatment of multiple myeloma, we compared
      the dissolution profile and plasma thalidomide concentrations of Japanese and
      British capsules and Mexican tablets. The dissolution test was performed
      according to the Japanese and the United States Pharmacopoeia. The
      pharmacokinetic data for Japanese capsules were obtained from the clinical trial
      in Japanese subjects and compared with those data published for other
      formulations. The dissolution rate of the Japanese capsule was the fastest,
      followed by British and Mexican formulations. The pharmacokinetic profiles of
      Japanese and British capsules were similar, while the 100 mg Japanese thalidomide
      capsule demonstrated a 1.6-fold higher maximum plasma concentration than the 200
      mg Mexican thalidomide tablet (1.7 vs. 1.1 microg/ml), greatly shortened t(max)
      (4.5 vs. 6.2 h), and the apparent half life was only one-third of the Mexican
      tablet (4.8 vs. 13.5 h). A comparison of the dissolution and the pharmacokinetic
      absorption profiles demonstrated a rank-order correlation. Physicians and
      pharmacists should be aware of the probable alteration in plasma thalidomide
      concentration when switching to the Japanese capsule, especially from the Mexican
      tablet, and should monitor clinical response carefully.

PMID- 18827466
TI  - Evaluation of drug-drug interaction potential of beraprost sodium mediated by
      P450 in vitro.
AB  - Beraprost sodium (BPS), a chemically stable and orally active prostacyclin
      analogue used for the treatment of chronic occlusive disease and primary
      pulmonary hypertension, was investigated in terms of its drug-drug interaction
      mediated by cytochrome P450. In a metabolic enzyme characterization study using
      P450-expressing insect cell microsomes, beraprost (BP) was slightly metabolized
      in the presence of CYP2C8, but not metabolized by the other P450 isoforms
      (CYP1A2, [corrected] CYP2A6, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4, and
      CYP4A11) at a concentration of 20 microM. These results suggest that none of the
      P450 isoforms is a major metabolic enzyme of BP. In a P450 induction study using
      human hepatocytes, BP did not induce any P450 isoform (CYP1A2, CYP2C9, CYP2C19,
      and CYP3A4) at concentrations of 1-100 microM. Furthermore, in a P450 inhibition
      study using human liver microsomes, BP did not inhibit any P450 isoform (CYP1A2,
      CYP2A6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4) at concentrations of 0.05-1
      microM. Therefore it is concluded that BP is not involved in drug-drug
      interaction mediated by P450 isoforms.

PMID- 18827467
TI  - [Development and evaluation of fundamental education about Kampo medicine
      adopting an experimental program in clinical pharmacy using team-based format].
AB  - A model core curriculum was proposed by the government in 2001 that outlined the
      core structure for undergraduate medical education, in which a Kampo medicine
      educational program was established. The following year, it was introduced in
      pharmacy as well as medicine. For fourth-year students at Tokai Medical
      University, a lecture on Kampo herbal medicine, focusing on clinical pharmacy,
      was given using team- based learning. Students learned the fundamental mechanism
      of Kampo medicine through team discussions about their subjective assessment of
      herbal medicine "Keishito" using their sensory organs and comparing objective
      analysis data of the main ingredients of Cinnamomi Cortex. They found that
      knowledge about Kampo medicine can come not only from clinical trials but also
      from objective observation. Through this educational program, almost all had an
      increased interest in the possible therapeutic value of herbal medicine. The
      results of examinations on Kampo herbal medicine showed that this program
      motivated students, especially those who had less or little interest in Kampo
      medicine before the lecture. The lecture-style team-based format could also
      facilitate a mutually supportive atmosphere, because negative feelings and
      concerns regarding initial traditional medicine can freely be expressed. In
      future, pharmacists as medical staff will provide preventive and curative primary
      care; since, for example, the Japanese government is pressing forward to prevent
      metabolic syndrome, which is related to lifestyle, this project could not have
      been completed without the cooperation of health professionals such as
      pharmacists. The present educational program in Kampo medicine may also be
      recommended for clinical pharmacy education.

PMID- 18827468
TI  - optimization of extended zero-order release gliclazide tablets using D-optimal
      mixture design.
AB  - The objective of this study was to develop and optimize the gliclazide extended
      release formulations by using simultaneously combination of two hydrophilic
      polymers: HPMC K 15M and sodium alginate as retardant. D-Optimal mixture design
      was employed to evaluate the effect of HPMC (X(1)), lactose (X(2)), and sodium
      alginate (X(3)) concentrations on the release rate of gliclazide from the
      matrices. The drug release percent at 3, 6, 9 and 12 h were the target responses
      and were restricted to 20-30, 45-55, 70-80 and 90-100%, respectively. Response
      surface methodology and multiple response optimization utilizing the polynomial
      equation were used to search for the optimal formulation with specific release
      rate at different time intervals. Validation of the optimization study indicated
      high degree of prognostic ability of response surface methodology. The mechanism
      of drug release from optimized extended-release matrix tablets was followed by
      the zero-order release pattern. This study demonstrated that D-optimal mixture
      experimental design facilitated the formulation and optimization of extended
      release hydrophilic matrix systems of gliclazide.

PMID- 18827469
TI  - [Inhibitory effects of hybrid liposomes on the growth of gastric tumor cells
      established from cotton rats].
AB  - We established cell-line (CoRa 622 G6) of gastric carcinoma using cotton rats
      with spontaneous malignant gastric carcinoma with hypergastrinaemia. Inhibitory
      effects of hybrid liposomes (HL) composed of dimyristoylphosphatidylcoline (DMPC)
      and polyoxyethylene (n) dodecyl ether (C(12)(EO)(n): n=21, 23, 25) on the growth
      of CoRa 622 G6 cells were clarified on the basis of WST-1 assay. Fusion and
      accumulation of HL including fluorescence probe into CoRa 622 G6 cell membrane
      were clarified using confocal laser microscopy and total internal reflection
      fluorescence microscopy. Induction of apoptosis of CoRa 622 G6 cells after the
      treatment with HL was observed in fluorescence micrographs on the basis of
      Annexin-V binding assay and TUNEL method using confocal laser microscopy. The
      results in this study could contribute to the chemotherapy for patients with
      gastric carcinoma.

PMID- 18827470
TI  - [Frequency of decreased renal function between patients treated with brand and
      generic products of vancomycin hydrochloride injection].
AB  - The frequency of decreased renal function was compared between patients treated
      with brand and generic products of vancomycin injection (VCM) in a retrospective
      manner based on the clinical examination records archived in Okayama University
      Hospital. A total of 122 patients were found to have been solely treated with
      vancomycin injection for MRSA infection, and their examination records were
      analyzed. The renal function of those patients was evaluated based on the serum
      creatinine concentration (SCr), and patients whose SCr was maximally elevated
      above the defined upper limit of the normal range (1.20 mg/dl for males and 0.96
      mg/dl for females) were considered to show decreased renal function. Although the
      amount of VCM administered to patients was larger in the case of generic rather
      than brand products, the percentage of patients whose renal function was
      decreased during VCM treatment was not significantly different between the VCM
      products, in which 2 among 62 patients receiving the brand product and 4 among 60
      receiving the generic product were reported to show decreased renal function. It
      was additionally revealed that 3 of those 4 patients with a decreased renal
      function related to the generic product were not treated as instructed by the
      package insert, and their trough VCM concentration exceeded the recommended level
      of 10 microg/ml. With these findings, the brand and generic VCM products are
      considered to be similar regarding the adverse effect of decreasing renal
      function.

PMID- 18827471
TI  - [Analysis of designer drugs detected in the products purchased in fiscal year
      2006].
AB  - Many psychotropic substances are easily available in Japan via the Internet, thus
      the spread of drug abuse is becoming more serious problem. To avoid drug abuse,
      32 substances have been controlled in Japan since April in 2007 by the
      Pharmaceutical Affairs Law as designated substances (Shitei-Yakubutsu, classified
      as 11 tryptamines, 11 phenethylamines, 2 piperazines, 6 alkyl nitrites, 1
      diterpene and 1 plant). Although the distributions of these drugs have been
      decreased through this regulation, new designer drugs are still being found. In
      this study, we detected 7 designer drugs in 15 products, which purchased just
      before the amendment of the law, by NMR, GC-MS and LC-MS analyses. Three
      methylone derivertives (1-(3,4-methylenedioxyphenyl-2-(pyrrolidin-1-yl)-1
      pentanone: MDPV, 2-methylamino-1-(3,4-methylenedioxyphenyl)butan-1-one: bk-MBDB,
      2-ethylamino-1-(3,4-methylenedioxyphenyl)propan-1-one): bk-MDEA, a MDMA
      derivative (N-hydroxy-1-(3,4-methylenedioxyphenyl)-2-aminopropane: N-OH MDMA), a
      methamphetamine derivative (N-methyl-1-(4-fluorophenyl)propan-2-amine: N-Me-4
      FMP), a tryptamine derivative (5-methoxy-N-ethyl-N-isopropyltryptamine: 5-MeO
      EIPT) and indan-2-amine were detected. 5-MeO-EIPT was newly identified in this
      study.

PMID- 18827472
TI  - Detection of levorotatory methamphetamine and levorotatory amphetamine in urine
      after ingestion of an overdose of selegiline.
AB  - In this study, we measured the urine concentrations of methamphetamine and
      amphetamine as metabolites of selegiline after ingestion of an overdose of
      selegiline. A patient who had developed Parkinson disease took selegiline in a
      suicide attempt. Analysis by gas chromatography-mass spectrometry (GC-MS) with
      trifluoroacetic acid-derivatization revealed the presence of methamphetamine and
      amphetamine in the patient's urine at concentrations of 0.62 microg/ml and 0.25
      microg/ml, respectively. To determine the stereospecificity of the
      methamphetamine and amphetamine, a urine sample was analyzed by GC-MS after
      derivatization with N-(trifluoroacetyl)-l-prolyl chloride. The methamphetamine
      and amphetamine were levorotatory in form. The ratio of the methamphetamine to
      amphetamine concentration in the urine was 2.5. This value is consistent with
      other case reports of ingestion of selegiline, which suggests that the
      methamphetamine to amphetamine concentration ratio in urine is useful information
      for indicating use of selegiline.

PMID- 18827473
TI  - [NMR analysis of a contaminant in heparin].
AB  - Recently, it has been reported that certain lots of heparin are associated with
      an acute, rapid onset of serious side effects indicative of allergic reaction,
      and (1)H NMR is one of the convenience but strong analytical methods to identify
      a contaminant in heparin. However, an NMR signal from the contaminant in some
      cases is overlapped with a satellite peak from heparin, leading a
      misunderstanding of the presence of the contaminant. Here, we show the satellite
      peak observed close to the NMR signal of the contaminant, and recommend the (13)C
      decoupling NMR to discriminate the satellite peak from the contaminant.

PMID- 18827474
TI  - Pegylated interferon plus ribavirin combination therapy for chronic hepatitis C
      in patients with congenital coagulation disorders.
AB  - Chronic hepatitis C (CHC) and end-stage liver disease are becoming an
      increasingly common cause of mortality in patients with congenital bleeding
      disorders, especially in the HIV-coinfected group. Combination of pegylated
      interferon (Peg-IFN) and ribavirin has recently become the treatment of choice
      for CHC. In this study, we evaluated the safety and efficacy of combination
      therapy with Peg-IFN plus ribavirin for the treatment of CHC in human
      immunodeficiency virus (HIV)- and HIV+ patients with congenital bleeding
      disorders. Between 2000 and 2004, 50 (18-68 years old) patients with CHC (19
      HIV+) from two hemophilia centers were included in the study. They were treated
      with weekly subcutaneous administration of Peg-INF-alpha combined with 800-1,200
      mg ribavirin daily, for 24-48 weeks depending on viral genotype. Response was
      evaluated at weeks 12, 24, 48 (end of treatment response) and 72 had sustained
      virological response). Overall, 22/50 patients (43.8%) had end of treatment
      response and 20/50 (40%) sustained virological response. HIV- patients responded
      similarly to the general population (58.1%), while HIV+ patients had very low
      response rates (10.5%). The high rate of discontinuation (36.9%) as a result of
      side effects contributed to the observed low response rate in the HIV+ group. The
      only factor strongly associated with sustained virological response in the HIV-
      patients was the reduction of HCV RNA at 12 weeks (p = 0.001). Patients with
      viral genotypes other than 1 had higher SVR rates, but this was not found to be
      statistically significant. Peg-INF plus ribavirin is safe for the treatment of
      CHC monoinfected patients with inherited bleeding disorders, with similar
      response rates to nonhemophiliacs. On the contrary, in HIV coinfected hemophilic
      patients under highly active antiretroviral therapy it is associated with severe
      toxicity and very poor sustained virological response rates. Careful evaluation
      and several considerations are needed before starting treatment in this
      population.

PMID- 18827475
TI  - Deferasirox treatment improved the hemoglobin level and decreased transfusion
      requirements in four patients with the myelodysplastic syndrome and primary
      myelofibrosis.
AB  - Transfusion-induced iron overload is a frequent problem that clinicians have to
      face in the treatment of patients affected by both myelodysplastic syndrome (MDS)
      and primary myelofibrosis (PMF). Different options are currently available for
      chelation therapy, e.g. oral once-daily administration of the iron chelator
      deferasirox. In 3 patients with MDS and 1 patient with PMF, deferasirox therapy
      resulted in an improvement in the hemoglobin level and a reduction in transfusion
      dependence. Our data open new insights regarding the benefit of iron chelation
      therapy not only for transfusional iron overload of myelodysplastic and
      myelofibrotic patients but also for the increase in hemoglobin levels. The
      biological mechanism of action of deferasirox, an effect which is not shared by
      other iron chelators, is still obscure and requires further investigations.

PMID- 18827476
TI  - Serum homocysteine: relationship with circulating levels of cortisol and
      ascorbate.
AB  - BACKGROUND/AIM: High serum levels of homocysteine and cortisol are independent
      risk factors for several pathologies and their levels can be regulated by some
      vitamins. Since the relationship between serum concentrations of homocysteine,
      cortisol and ascorbate has not been assessed in healthy individuals to date, it
      was the topic of the present work. METHODS: The study group was composed of 20
      men and 40 women aged >50 years. Blood samples were collected and serum
      concentrations of the analytes were quantified. RESULTS: Serum homocysteine
      levels correlate positively with cortisol (r = 0.36, p <0.01) and age (r = 0.49,
      p < 0.001), and negatively with ascorbate (r = -0.30, p < 0.05) and folate (r = 
      0.31, p < 0.05). A negative correlation between serum levels of cortisol and
      ascorbate (r = -0.30, p < 0.05) was also observed. Multiple linear regression
      analysis showed that the best independent predictors of serum homocysteine
      concentration were cortisol (beta = 0.319, p < 0.003), age (beta = 0.529, p <
      0.001) and folate (beta = -0.338, p < 0.001). When subjects were divided into
      tertiles according to their homocysteine concentration, the highest tertile of
      homocysteine concentration has also higher cortisol (p < 0.005) and lower
      ascorbate (p < 0.05) concentrations compared with the lowest tertile of
      homocysteine concentration. CONCLUSION: The association between serum
      concentrations of homocysteine, cortisol and ascorbate suggests interaction
      between circulating levels of these molecules.

PMID- 18827477
TI  - Reversible conductive hearing loss: restored activity in the central auditory
      system.
AB  - The effect of a reversible, unilateral hearing loss on 2-deoxyglucose (2-DG)
      uptake in the central auditory system was studied using young gerbils. All
      animals had a unilateral conductive hearing loss (CHL), induced by atresia, on
      postnatal day 21 (P21). One week later, on P28, animals had their atresia
      repaired (CHL/R), or not repaired (CHL/NR), and CHL/NR animals entered the 2-DG
      experiments. CHL/R animals were allowed a 1-week period of restored binaural
      hearing experience prior to entering 2-DG experiments on P35. Animals in each
      group were injected with 2-DG and exposed to ambient sounds for 45 min prior to
      sacrifice. Uptake of 2-DG was measured in the anteroventral cochlear nucleus
      (AVCN), the medial superior olive (MSO), and the inferior colliculus (IC) on both
      sides of the brain. In CHL/NR animals, there were significant differences in
      uptake between the AVCN, MSO, and IC ipsilateral versus contralateral to the
      manipulated ear, indicating an imbalance in ascending afferent activity. In CHL/R
      animals, there were no significant differences, suggesting that 1 week after CHL
      repair, the appearance of balanced afferent activity had been restored.

PMID- 18827478
TI  - Effects of fixative and embedding medium on morphology and immunostaining of the
      cochlea.
AB  - The localization of proteins by immunostaining is a powerful method to
      investigate otologic disorders. However, the use of fixatives and embedding media
      (necessary for the preservation of morphology) can obscure antigens, making it
      difficult to perform immunoassays. We performed a systematic investigation of the
      effects of fixative and embedding medium on morphology and immunostaining of the
      mouse cochlea. Three different fixative solutions [4% formaldehyde (F), 4%
      formaldehyde + 1% acetic acid (FA), and 4% formaldehyde + 1% acetic acid + 0.1%
      glutaraldehyde (FGA)] and 3 different embedding media (paraffin, polyester wax,
      and celloidin) were used. Morphology was assessed using light microscopy.
      Immunostaining was studied using a panel of 6 antibodies (to prostaglandin D
      synthase, aquaporin 1, connective tissue growth factor, 200-kDa neurofilament,
      tubulin and Na(+),K(+)-ATPase). Preservation of morphology was suboptimal with
      paraffin, adequate with polyester wax and superb with celloidin. Immunostaining
      was successful using all 6 antibodies in all 3 fixatives and all 3 embedding
      media. While there were differences in strength of signal and localization of
      antigen between the 3 fixatives, overall, FA and FGA gave the most uniform
      results. For a given fixative and antibody, there was surprisingly little
      difference in the quality of immunostaining between celloidin and paraffin, while
      results in polyester wax were not as good in some cases. These results suggest
      that celloidin may be the embedding medium of choice for both morphological and
      pathological studies, including immunostaining when morphology must be optimized.

PMID- 18827479
TI  - Auditory brainstem correlates of basilar membrane nonlinearity in humans.
AB  - A behavioral measure of the basilar membrane response can be obtained by
      comparing the growth in forward masking for maskers at, and well below, the
      signal frequency. Since the off-frequency masker is assumed to be processed
      linearly at the signal place, the difference in masking growth with level is
      thought to reflect the compressive response to the on-frequency masker. The
      present experiment used an electrophysiological analog of this technique, based
      on measurements of the latency of wave V of the auditory brainstem response
      elicited by a 4-kHz, 4-ms pure tone, presented at 65 dB SPL. Responses were
      obtained in quiet and in the presence of either an on-frequency (4 kHz) or an off
      frequency (1.8 kHz) pure-tone forward masker. Wave V latency increased with
      masker level, although the increase was greater for the off-frequency masker than
      for the on-frequency masker, consistent with a more compressive response to the
      latter. Response functions generated from the data showed the characteristic
      shape, with a nearly linear response at lower levels and 4:1 compression at
      higher levels. However, the breakpoint between the linear region and the
      compressive region was at about 60 dB SPL, higher than expected on the basis of
      previous physiological and psychophysical measures.

PMID- 18827480
TI  - Expression and localization of K channels KCNQ2 and KCNQ3 in the mammalian
      cochlea.
AB  - KCNQ1 and KCNQ4 voltage-gated potassium channel subunits play key roles in
      hearing. Other members of the KCNQ family also encode slow, low voltage-activated
      K(+) M currents. We have previously reported the presence of M-like K(+) currents
      in sensory hair cells, and expression of Kcnq family genes in the cochlea. Here,
      we describe Kcnq2/3 gene expression and distribution of M channel subunits KCNQ2
      and 3 in the cochlea. By using RT-PCR, we found expression of Kcnq2 in the
      modiolus and organ of Corti, while Kcnq3 expression was also detected in the
      cochlear lateral wall. Five alternative splice variants of the Kcnq2 gene, one of
      which has not been reported previously, were identified in the rat cochlea. KCNQ2
      and KCNQ3 immunoreactivities were observed in spiral ganglion auditory neurons.
      In addition, the unmyelinated parts of the nerve fibers innervating hair cells
      and synaptic regions under hair cells showed KCNQ2 immunoreactivity. KCNQ3
      immunoreactivity was also prominent in spiral ganglion satellite cells. These
      findings suggest that cochlear M channels play important roles in regulation of
      cellular excitability and maintenance of cochlear K(+) homeostasis in the
      auditory system.

PMID- 18827481
TI  - Effect of the polymorphism of tumor necrosis factor-alpha-308 G/A gene promoter
      on the susceptibility to ulcerative colitis: a meta-analysis.
AB  - BACKGROUND: Ulcerative colitis (UC) is a complex polygenic disease in which gene
      environment interactions are important. Some studies have reported that
      proinflammatory polymorphisms in tumor necrosis factor-alpha-308 (TNF-alpha-308)
      gene promoter (substitution G-->A, designated as TNF1 and TNF2) is associated
      with increased UC risk. However, the results of individual studies have been
      inconsistent. METHODS: To investigate the inconsistent findings in studies of the
      association of the polymorphism of TNF-alpha-308 gene promoter with
      susceptibility to UC, a systematic review of the published data was undertaken
      and a meta-analysis was performed. The MEDLINE database was searched for case
      control studies published in English language journals from 1966 to November
      2007. Data were extracted using standardized forms and odds ratios (OR) with 95%
      confidence intervals (CI) were calculated. RESULTS: 15 eligible studies, 7 of
      Europeans, 2 of Americans, and 6 of Asians including 4 East Asians, were included
      in the meta-analysis. An association between UC and TNF2 allele was not found in
      the overall population (OR 1.28, 95% CI 0.84-1.96, p = 0.25). However,
      stratification by ethnicity indicated that there was significant association
      between TNF2 allele and UC in East Asians (OR 2.27, 95% CI 1.08-4.77, p = 0.03).
      Conversely, there was no association between TNF2 allele and UC patients from the
      European (OR 0.85, 95% CI 0.42-1.71, p = 0.65) and Asian samples (OR 1.64, 95% CI
      0.98-2.74, p = 0.06). The OR for the TNF2/2+TNF2/1 genotype versus TNF1/1
      genotype in samples overall and in each ethnic group showed a similar trend to
      those for the TNF2 allele. CONCLUSION: In East Asians, the TNF2 allele confers a
      significant risk for developing UC. There is no association between the
      polymorphism of TNF-alpha-308 gene promoter and UC in Europeans.

PMID- 18827482
TI  - Seborrheic area erythema as a common skin manifestation in Japanese patients with
      dermatomyositis.
AB  - BACKGROUND: Although dermatomyositis (DM)-associated facial erythema was noted in
      the nasolabial folds of Japanese patients, DM-associated facial erythema other
      than heliotrope rash has drawn little attention in previous studies. OBJECTIVES:
      To characterize phenotypical features and frequencies of erythema, especially
      those in the seborrheic area of the head, in DM patients. METHODS: A
      retrospective study on skin manifestations in 33 DM patients followed up at our
      department during the past 15 years was conducted. RESULTS: Macular violaceous
      erythema (MVE) in the seborrheic area of the face was most frequent (67%).
      Patients with facial MVE had also MVE in the scalp significantly more frequently
      than those without facial MVE. The pathology of the facial MVE was dominated by
      DM-associated changes with slight changes compatible with seborrheic dermatitis
      (SD). CONCLUSIONS: Japanese DM patients had MVE frequently in the seborrheic area
      of the head. Its phenotypical features suggested that it might be triggered by
      SD.

PMID- 18827483
TI  - Prurigo in dermatomyositis.

PMID- 18827484
TI  - Hepatocellular carcinoma with hepatic venous obstruction and hepatic venous
      collaterals.

PMID- 18827485
TI  - Miliary hepatic metastases from neuroendocrine carcinoma.

PMID- 18827486
TI  - Pneumatosis intestinalis and hepatico-portal-mesenteric-splenic venous gas.

PMID- 18827487
TI  - Uncommon giant submucosal tumor of stomach.

PMID- 18827488
TI  - Changes in outcome during implementation of a fast-track colonic surgery project
      in a university-affiliated general teaching hospital: advantages reached with
      ERAS (Enhanced Recovery After Surgery project) over a 1-year period.
AB  - BACKGROUND AND AIMS: The aim of this study was to investigate whether changes can
      be accomplished rapidly after implementing a fast-track colonic surgery project
      at a university-affiliated general teaching hospital. METHODS: In 2004 and 2005
      all colonic surgery patients were recorded for a number of pre-, per- and
      postoperative care elements. In 2006, during the implementation of a fast-track
      program, changes were recorded. RESULTS: Before the implementation of the fast
      track regime at our hospital, 97% of the patients (n = 89/92) received mechanical
      bowel preparation, in contrast to 3% (n = 1/36) afterwards (p < 0.0001). The
      application of thoracic epidural analgesia rose from 46% (n = 42/92) in 2004 and
      2005 to 94% (n = 34/36) in 2006 (p < 0.0001). The use of nasogastric tubes
      postoperatively almost disappeared. 77% (n = 28/36) enjoyed a small meal on the
      1st day after operation, compared to 0% (n = 0/92) in 2004 and 2005 (p < 0.0001).
      Median hospital stay was 6 (range 3-27) nights in 2006 compared to 9 (range 3-25)
      nights in 2005 and 9.5 (range 7-64) nights in 2004 (p < 0.005). CONCLUSION: These
      preliminary results show that also at a district general teaching hospital
      advantages can be reached rapidly and safely by implementing fast-track surgery;
      especially a faster recovery.

PMID- 18827489
TI  - Decision making for relaparotomy in secondary peritonitis.
AB  - BACKGROUND/AIMS: To provide a qualitative ranking of clinical variables by
      surgeons that influence their decision for reoperation and to evaluate whether
      these variables are related to positive findings at relaparotomy. METHODS:
      Importance in decision making for relaparotomy was evaluated for 21 factors using
      a 10-point visual analogue scale (VAS). Variables with median VAS scores >5.0
      were labeled 'important'. Predictive value for positive findings was evaluated by
      multivariate analysis. RESULTS: The response rate was 64%. For each variable, a
      wide range of VAS scores was given. Of variables labeled 'important', a diffuse
      extent of abdominal contamination (odds ratio, OR 1.9; 95% CI 0.99-3.8; p =
      0.052), localization of the infectious focus (upper gastrointestinal tract
      including small bowel: OR 2.6, 95% CI 0.98-7.0, p = 0.055; colon: OR 2.4, 95% CI
      0.93-6.0, p = 0.071), and both low (<3 x 10(9)/l: OR 4.6, 95% CI 1.3-17, p =
      0.021) and high (>20 x 10(9)/l: OR 2.2, 95% CI 1.0-4.9, p = 0.042) leukocyte
      counts independently predicted positive relaparotomy. As a set, these variables
      had only moderate predictive accuracy (c-statistic 0.69). CONCLUSIONS: There was
      no consensus among surgeons which variables were important in decision making for
      relaparotomy. Only three out of ten variables labeled as 'important' were indeed
      independently predictive, but even as a set had only moderate predictive
      accuracy.

PMID- 18827490
TI  - Blood loss during transvaginal oocyte retrieval.
AB  - BACKGROUND/AIMS: Limited information is available regarding the quantity of blood
      loss associated with uncomplicated transvaginal oocyte retrieval. The aim of the
      present study was evaluating the quantity of such a loss. METHODS: One hundred
      and fifty consecutive women undergoing oocyte retrieval were recruited. They
      underwent blood test assessment and ultrasonographic transvaginal evaluation at
      three different times: (1) immediately before initiating oocyte retrieval, (2) 4
      6 h later, and (3) 72 h later. RESULTS: At 4-6 h after oocyte retrieval, the red
      blood cell count and the hemoglobin concentration were significantly reduced,
      whereas pelvic free fluid had significantly increased. The estimated median
      (Interquartile range) blood loss was 72 (-8/162) ml. None of the recruited women
      was found to have a hemoglobin reduction >2 g/day or an increase in the pelvic
      free fluid >200 ml or a calculated blood loss >500 ml (0.0%, 95% CI: 0.0-2.4%).
      No significant worsening from baseline was observed at the 72 h evaluation.
      CONCLUSIONS: The quantity of blood loss following oocyte retrieval is clinically
      unremarkable in the vast majority of women.

PMID- 18827491
TI  - Back pain symptoms and bone mineral density changes in pregnancy as measured by
      quantitative ultrasound.
AB  - OBJECTIVE: To evaluate whether back pain symptoms in pregnancy are associated
      with bone mineral density (BMD) changes as measured by quantitative ultrasound at
      the os calcis. METHODS: Consecutive patients were recruited from a general
      obstetric clinic over 1 year. Quantitative ultrasonographic measurements of BMD
      were performed at the os calcis between weeks 14-20 and 36-38. They were then
      surveyed for back pain symptoms experienced during pregnancy in the early
      postpartum period, and these were subsequently correlated with BMD changes.
      RESULTS: Of a total of 463 patients, 231 (49.8%) reported one or more episodes of
      significant back pain during pregnancy. A mean fall in BMD of 0.0395 g/cm(2) was
      demonstrable from early to late gestation. Those with back pain symptoms have
      higher mean BMD loss at the os calcis during pregnancy compared to those without
      back pain (0.038 vs. 0.029 g/cm(2); p = 0.012). A logistic regression model
      showed that weight gain and BMD loss in pregnancy were significantly associated
      with back pain symptoms. CONCLUSION: Back pain symptoms in pregnancy were
      associated with a greater fall in BMD at the os calcis, supporting the hypothesis
      that BMD changes could have an etiological role in back pain during pregnancy.

PMID- 18827492
TI  - A treatment selection protocol for recurrent ovarian cancer patients: the role of
      FDG-PET/CT and staging laparoscopy.
AB  - OBJECTIVE: To investigate the best diagnostic and staging strategy for recurrent
      ovarian cancer. METHODS: The negative predictive value, specificity, positive
      predictive value, sensitivity, and accuracy rates of the fluorine-18
      fluorodeoxyglucose positive emission tomography computed tomography (FDG-PET/CT)
      and staging laparoscopy in identifying surgically treatable/untreatable patients
      are assessed in a consecutive series of 70 recurrent ovarian cancer cases.
      Moreover, the diagnostic performance of each staging procedure in the evaluation
      of the number of nodules is analyzed. RESULTS: The negative predictive value of
      the FDG-PET/CT was 83.3%, whereas the positive predictive value was 76.9%.
      Specificity was 55.6%, whereas sensitivity was 93.0%. Accuracy rate was 78.6%.
      Negative predictive value, specificity, positive predictive value, sensitivity,
      and accuracy rate of staging laparoscopy were 88.9, 64.0, 80.8, 95.0 and 83.1%,
      respectively. Combined radiological and laparoscopic evaluation showed a negative
      predictive value of 88.9%, a specificity of 59.3%, a positive predictive value of
      78.8%, a sensitivity of 95.3%, and an accuracy rate of 81.4%. The number of
      nodules identified by FDG-PET/CT corresponded in only 23 patients (40.3%) at
      laparotomy, whereas 15 of 30 patients were correctly diagnosed (50.0%) by staging
      laparoscopy. CONCLUSIONS: The combination of FDG-PET/CT and staging laparoscopy
      has a significant effect on the multimodal approach to the population of patients
      with recurrent ovarian cancer. Such techniques should be considered
      complementary, because of the potential of each one to identify a different
      setting of the disease.

PMID- 18827493
TI  - Role of AIB1 for tamoxifen resistance in estrogen receptor-positive breast cancer
      cells.
AB  - OBJECTIVES: The p160 nuclear receptor coactivator, AIB1 (amplified in breast
      cancer 1), is frequently overexpressed in human breast cancer and has been shown
      to be associated with tamoxifen resistance. The present study aimed to
      investigate the role of AIB1 in tamoxifen resistance of breast cancer cells.
      METHODS: We reconstructed the RNA interference expression vector, pGenesil-1-U6,
      specially targeting AIB1 mRNA, and it was stably transfected into the human
      breast cancer cell line BT474. Cell proliferation and cell cycle distribution
      were assessed in the cells transfected with scramble control shRNA
      (BT474/shControl) and AIB1 shRNA (BT474/shAIB1) to explore the possible functions
      of AIB1 in breast cancer progression. The expression of AIB1, ERalpha, HER2 and
      pS2 was analyzed in the presence of 17beta-estradiol or 4-hydroxytamoxifen (Tam)
      by Western blot analysis. RESULTS: Compared with the parental BT474 and the
      BT474/shControl cells, the levels of AIB1 mRNA and protein were significantly
      reduced in BT474/shAIB1 cells. A knockdown of AIB1 levels restored the inhibitory
      effect of tamoxifen on cell proliferation. CONCLUSIONS: Tam behaves like an
      estrogen agonist in ER-positive breast cancer cells that express high levels of
      AIB1 and HER2, resulting in de novo resistance. Knockdown of AIB1 can eliminate
      this cross talk and restore the antitumor effects of tamoxifen.

PMID- 18827494
TI  - Gender differences in treatment outcomes among patients with non-small cell lung
      cancer given a combination of carboplatin and paclitaxel.
AB  - OBJECTIVES: It was the aim of this study to investigate gender differences in the
      outcomes of carboplatin and paclitaxel chemotherapy in patients with unresectable
      stage IIIB-IV non-small cell lung cancer (NSCLC). METHODS: Gender, age,
      performance status, histology, hematological toxicity, tumor responses and
      survival parameters obtained retrospectively by medical chart review were
      analyzed. RESULTS: A total of 227 patients (147 males and 80 females) were
      included. The median lowest leukocyte count was 2,900 (range 1,200-12,400)/microl
      in males and 2,200 (range 600-6,500)/microl in females (p < 0.001). Grade 3-4
      leukopenia was noted in 15% of male and in 39% of female patients (p < 0.001). In
      both genders, the response rate in evaluable patients was 39%. The median
      progression-free survival was 4.4 months for men and 5.3 months for women (p =
      0.0081). After progression of the disease, gefitinib was administered in 64 (44%)
      male and 45 (56%) female patients, with a median treatment of 35 and 144 days,
      respectively. The median survival time was 11.9 months for men and 22.2 months
      for women (p < 0.001). CONCLUSION: Female gender was associated with a favorable
      prognosis in patients with NSCLC who received carboplatin and paclitaxel
      chemotherapy, although the response rates did not differ between the genders. Of
      note, hematological toxicity was more severe in female patients.

PMID- 18827495
TI  - [Estimating the economic burden of osteoporotic vertebral fracture among elderly
      Korean women].
AB  - OBJECTIVES: To estimate the economic burden of osteoporotic vertebral fracture
      (VF) from a societal perspective. METHODS: From 2002 to 2004, we identified all
      National Health Insurance claims records for women >or= 50 years old with a
      diagnosis of VF. The first 6-months was defined as a "clearance period," Ysuch
      that patients were considered as incident cases if their first claim of fracture
      was recorded after June 30, 2002. We only included patients with >or= one claim
      of a diagnosis of, or prescription for, osteoporosis over 3 years. For each
      patient, we cumulated the claims amount for the first visit and for the follow-up
      treatments for 1 year. The hospital charge data from 4 hospitals were
      investigated to measure the proportion of the non-covered services. Face-to-face
      interviews were conducted with 106 patients from the 4 study sites to measure the
      out-of-pocket spending outside of hospitals. RESULTS: During 2.5 years, 131,453
      VF patients were identified. The patients had an average of 3.38 visits, 0.40
      admissions and 6.36 inpatient days. The per capita cost was 1,909,690 Won: 71.5%
      for direct medical costs, 20.6% for direct non-medical costs and 7.9% for
      indirect costs. The per capita cost increased with increasing age: 1,848,078 Won
      for those aged 50-64, 2,084,846 Won for 65-74, 2,129,530 Won for 75-84 and
      2,121,492 Won for those above 84. CONCLUSIONS: Exploring the economic burden of
      osteoporotic VF is expected to motivate to adopt effective treatment options for
      osteoporosis in order to prevent the incidence of fracture and the consequent
      costs.

PMID- 18827496
TI  - [The effect of the cost exemption policy for hospitalized children under 6 years
      old on the medical utilization in Korea].
AB  - OBJECTIVES: The Korean government in January 2006 instigated an exemption policy
      for hospitalized children under the age of six years old. This study examines how
      this policy affected the utilization of medical care in Korea. METHODS: A total
      of 1,513,797 claim records from the Health Insurance Review Agency were analyzed
      by complete enumeration methods. The changes of medical utilization were compared
      from 2005 to 2006. In addition, the changes of medical utilization between 2004
      and 2005 were compared as a pseudo-control group. RESULTS: The admission rate
      increased 1.14-fold from 15.20% in 2004 to 17.32% in 2005, and this further
      increased 1.08-fold to 18.65% in 2006. The increase of patients with a common
      cold (1.2-fold) was higher than that of both the general patients (1.08-fold) and
      the patients with the top 10 fatal diseases (0.91-fold). The average length of
      stay per case for clinics showed the highest increase rates (1.06-fold). The
      rates of patients with the common cold showed a higher increase (1.05-fold) than
      that of the general patients. The average medical expense per case was increased
      by 1.10-fold from 2005 to 2006, which was higher than that from 2004 to 2005
      (1.04-fold). The increase rate for patients with the common cold was higher at
      1.18-fold than that of the general patients. CONCLUSIONS: The cost exemption
      policy has especially led to an increase in the utilization of clinics and the
      utilization by patients with a common cold.

PMID- 18827497
TI  - [Comparisons of health inequalities in small areas with using the standardized
      mortality ratios in Korea].
AB  - OBJECTIVES: This study was performed to compare the standardized mortality ratios
      among different small areas and to explore the usefulness of standardized
      mortality ratios in South Korea. METHODS: To calculate the standardized mortality
      ratio (SMR), we obtained the national deaths certificate data (2004-2006) and
      national registration population data (2003-2006), and these were provided by the
      National Statistical Office. The small areas (Eup.Myoun.Dong) were based on the
      subdivisions of counties. Among the 3,580 small areas classified by the National
      Statistical Office, 3,571 areas were included in this study. The basic statistics
      and decile distributions of the SMRs for all the regional levels were calculated,
      and the small area maps were also produced for some selected regions. To evaluate
      the precision of SMR, we calculated the 95% confidence intervals of the SMR in
      selected small areas. RESULTS: The mean and the standard deviation of the SMRs
      among all small areas were 100.8 and 17.0, respectively. The range was 30.6-211.7
      and the inter-quartile range was 20.7. Seoul metropolitan city displayed the
      lowest mean SMR among 16 regions in South Korea, and 34.6 percent of the small
      area SMRs belonged to the first decile (the lowest group). On the contrary, the
      mean SMR of Gyeongsangnam province was highest, and 26.1 percent of the small
      area SMRs belonged to the tenth decile(the highest group). In some areas, the
      precision of the SMR, which was calculated by the 95% confidence intervals,
      remained questionable, yet it was quite stable for almost areas. CONCLUSIONS: The
      standardized mortality ratios can be useful for allocating health resources at
      the small area level in Korea.

PMID- 18827498
TI  - [Study on the health status of the residents near military airbases in Pyeongtaek
      City].
AB  - OBJECTIVES: We conducted an epidemiologic survey to evaluate the effect of the
      aircraft noise exposure on the health of the residents near the military airbases
      in Pyeongtaek City. METHODS: The evaluation of environmental noise level,
      questionnaire survey, and health examination were performed for 917 residents.
      The study population consisted of four groups: subjects who lived in the village
      close to the fighter airbase (high exposure), subjects who lived along the course
      of fighters (intermediate exposure), and subjects near a helicopter airbase, and
      the control group. RESULTS: The prevalence of the aircraft noise related accident
      and irritable bowel syndrome in the exposure groups were higher than that of the
      control group. The risks of noise induced hearing loss, hypertension and diabetes
      mellitus were higher in the exposed groups than in the control group. The
      prevalence of anxiety disorder and primary insomnia were higher in the exposed
      groups than in the control group. Prevalence odd ratios of the risk for primary
      insomnia after adjusting age, sex, agricultural noise, and occupation were 4.03
      [95% confidence interval (95% CI) 1.56-10.47] for the subject near the helicopter
      airbase, 1.23 (95% CI 0.40-3.76) for those intermediately exposed to fighter
      noise, and 4.99 (95% CI 2.14-11.64) for those highly exposed to fighter noise.
      CONCLUSIONS: The results of the present study suggest that the aircraft noise may
      have adverse effects on hearing function, cardiovascular health and mental
      health. Therefore, it seems to be needed to take proper measures including the
      control of the aircraft noise and the management of the exposed people's health.

PMID- 18827499
TI  - [How are consumers, service and market factors related to customer loyalty in
      medical service? Targeting the medical consumer in a city].
AB  - OBJECTIVES: This study was performed to explore customer loyalty and the related
      factors. METHODS: 900 households (a 1% sample) were randomly selected from the
      total population of K city located in Kangwon province. An interview survey was
      performed with using a structured questionnaire for the subjects (923 persons)
      who had used medical service during the year before the survey, and the survey
      was done September, 2002. RESULTS: When comparing the relating factors related
      with customer loyalty according to the sociodemographic characteristics, the
      older group showed a significantly higher level of recognition for service
      quality, service reputation, internal customers.attitudes and switching cost. The
      lower income group showed a higher level of recognition for service quality,
      service image and switching cost. The lower educated group showed a higher level
      of recognition for service reputation, service image and internal
      customers.attitudes. The higher educated group showed a higher level of
      recognition for perceived risk, and seeking variety. In addition, the expert
      group or the service and manufacturing workers group showed a higher level of
      recognition for service involvement. On multiple regression analysis, internal
      customers' attitudes, service image, service reputation, service quality,
      switching cost, and substitutability showed significant relations with customer
      loyalty. CONCLUSIONS: This study showed that customer loyalty was significantly
      influenced by service factors like internal customers' attitudes, service image,
      service reputation, and service quality, and by market factors like switching
      cost, and substitutability. The results of this study can be used as a baseline
      for developing strategies to create and keep customers with high loyalty.

PMID- 18827500
TI  - The effects of actual and perceived body weight on unhealthy weight control
      behaviors and depressed mood among adult women in Seoul, Korea.
AB  - OBJECTIVES: This study was conducted to examine the mediating function of body
      weight perception (BWP) on the relationship between body mass index (BMI) and
      unhealthy weight control behaviors (UWCB: e.g., fasting, or taking diet pills or
      laxatives) and between BMI and depressed mood, and to explore the effect of
      distorted BWP on UWCB and depressed mood among adult women. METHODS: A regionally
      representative sample of 8,581 women aged 20-64 years residing in Seoul, the
      capital of Korea, completed the 2001 Seoul Citizens Health Indicator Survey which
      provides self-reported information about height, weight, BWP, UWCB, depressed
      mood, demographic/ socioeconomic characteristics, and health-related behaviors.
      Data were analyzed using bivariate and multivariate logistic regression. RESULTS:
      BMI was significantly associated both with UWCB and depressed mood, even
      controlling for all covariates. However, the magnitude and significance of each
      association was considerably attenuated when BWP was taken into account,
      indicating that BWP functioned, in part, as a mediator between BMI and UWCB and
      between BMI and depressed mood, respectively. Among the combinations of BMI and
      BWP, women who perceived themselves to be heavier than their actual BMIs appeared
      more likely to use UWCB, whereas women who had a distorted BWP, either
      underestimation or overestimation as compared with their BMIs, tended to be at
      greater risk for depressed mood than those who had an undistorted BWP.
      CONCLUSIONS: These findings suggest that how women perceive their body weight may
      be an important predictor and/or mediator of UWCB and depressed mood among adult
      Korean women.

PMID- 18827501
TI  - [Measuring workload of home visit care activities using relative values].
AB  - OBJECTIVES: The purpose of this study was to measure the workload of home visit
      care activities and their relative values. This study examined also factors that
      affect the workload of home visit care activities. METHODS: The participants of
      this study were 126 home-helpers of 50 home visit care agencies at the 2nd
      Longterm Care Insurance Demonstration Project. The workload of home visit care
      activities was divided into total work and four dimensions; physical efforts,
      mental efforts, stress and time. Home visit care activities consisted of four
      categories with 24 items. We used magnitude estimation method to measure their
      relative values of the four dimensions. The participants answered the relative
      values of each activities based on the reference service. We used the activity
      for supporting their elderly's evacuation as the reference service. RESULTS: Most
      of the respondents were over 40 years old female. They consumed most their time
      supporting elderly's going out. They consumed their highest physical, mental
      efforts, and stress for activities of coping with emergency situation. The
      Pearson correlation coefficients showed significant relationships between
      workload and each dimensions. This study showed that all four dimensions are
      statistically significant predictors of workload of home visit care activities.
      Also, we found that the home-helper's career affects the workload of home visit
      care activities. CONCLUSIONS: The workload of home visit care activities could be
      explained by physical efforts, mental efforts, stress and time.

PMID- 18827502
TI  - ['Informed consent' in public health activities: based on the universal
      declaration on bioethics and human rights, UNESCO].
AB  - OBJECTIVES: The objective of this paper is to discuss the importance of obtaining
      informed consent for conducting epidemiological studies and public health
      activities, based on the Report of the UNESCO's Working Group on Informed
      Consent. METHODS: The Report of the UNESCO's Working Group on Informed Consent
      was reviewed and discussed in connection with the ethical considerations of
      public health activities and epidemiological research. RESULTS: It was at the
      Nuremberg Trial for the German war criminals of the Second World War that the
      principle of 'consent' was first stated as a consequence of the medical abuses
      carried out during the War. As a result of the Trial, the Nuremberg Code came out
      in 1947. Since then, various international declarations or ethical principles on
      'informed consent' have been developed and published. These ethical principles on
      'informed consent' have mostly to do with the clinical research that involves
      human subjects, and not with epidemiological studies and public health
      activities. However, UNESCO recently issued a comprehensive Report on Informed
      Consent based on the Universal Declaration on Bioethics and Human Rights adopted
      in 2005, and this included detailed guidelines on informed consent in
      epidemiological studies and public health activities. CONCLUSIONS: Universal
      Declaration on Bioethics and Human Rights emphasizes the principle of autonomy to
      protect the human rights of the human subjects involved in any public health
      activities and epidemiological research. As a practical guideline, obtaining
      informed consent is strongly recommended.

PMID- 18827503
TI  - [A literature review on health effects of exposure to oil spill].
AB  - OBJECTIVES: Our objective is to review and summarize the previous studies on the
      health effects of exposure to oil spills in order to make suggestions for mid-
      and long-term study plans regarding the health effects of the Hebei Spirit oil
      spill occurred in Korea. METHODS: We searched PubMed to systemically retrieve
      reports on the human health effects related to oil spill accidents. The papers'
      reference lists and reviews on the topic were searched as well. RESULTS: We found
      24 articles that examined seven oil spill accidents worldwide over the period
      from 1989 to August 2008, including the Exxon Valdes, Braer, Sea Empress, Erika,
      Nakhodka, Prestige and Tasman Spirit oil spills. Most of the studies applied
      cross-sectional and short-term follow-up study designs. The exposure level was
      measured by assessing the place of residence, using a questionnaire and
      environmental and personal monitoring. Studies on the acute or immediate health
      effects mainly focused on the subjective physical symptoms related to clean-up
      work or residential exposure. Late or mid-term follow-up studies were performed
      to investigate a range of health effects such as pulmonary function and
      endocrine, immunologic and genetic toxicity. The economic and social impact of
      the accidents resulted in the socio-psychological exposure and the psychosocial
      health effects. CONCLUSIONS: Studies of the health effects of exposure to oil
      spills should consider a range of health outcomes, including the physical and
      psychological effects, and the studies should be extended for a considerable
      period of time to study the long-term chronic health effects.

PMID- 18827504
TI  - [Multiple roles and health among Korean women].
AB  - OBJECTIVES: Most studies about multiple roles and women's health suggested that
      combining with paid job, being married and having children was more likely to
      improve health status than in case of single or traditional roles. We
      investigated whether there was better health outcome in multiple roles among
      Korean women coinciding with previous studies of other nations. METHODS: Data
      were from the 2005 Korea National Health & Nutritional Examination Survey, a
      subsample of women aged 25-59 years (N=2,943). Health status was assessed for
      self-rated poor health, perceived stress and depression, respectively based on
      one questionnaire item. The age-standardized prevalence of all health outcomes
      were calculated by role categories and socioeconomic status. Multiple logistic
      regression was used to assess the association of self rated health, perceived
      stress, and depression with multiple roles adjusted for age, education, household
      income, number of children and age of children. RESULTS: Having multiple roles
      with working role was not associated with better health and psychological
      wellbeing. Compared to those with traditional roles, employed women more
      frequently experienced perceived stress, with marital and/or parental roles. Non
      working single mothers suffered depression more often than women with traditional
      roles or other role occupancy. Socioeconomic status indicators were potent
      independent correlates of self-rated health and perceived stress. CONCLUSIONS:
      Employment of women with other roles did not confer additional health benefit to
      traditional family responsibility. Juggling of work and family responsibility
      appeared more stressful than traditional unemployed parental and marital role in
      Korean women.

PMID- 18827505
TI  - Evidence-based voting.

PMID- 18827508
TI  - The new NIH public access policy.

PMID- 18827513
TI  - State of the Science of NNP Education 2008.

PMID- 18827514
TI  - Oxygen free radicals: effects in the newborn period.
AB  - Free radical production occurs continuously in all cells as a by-product of cell
      metabolism. In tandem, the human body has developed endogenous antioxidant
      systems as well as taken advantage of dietary exogenous antioxidants to process
      and detoxify free radicals appropriately. However, certain conditions may
      increase free radical production beyond the body's endogenous and exogenous
      antioxidant systems. The neonatal period is a vulnerable time for free radical
      damage and injury, particularly for preterm infants whose antioxidant defense
      systems have not fully matured. Endogenous and passively acquired exogenous
      antioxidant defense systems do not accelerate in maturation until late in the
      third trimester. To explore the complexities of these concepts, this article
      includes a description, an evolutionary perspective of oxygen, and a basic
      background on free radical chemistry in biology. In addition, this chemistry is
      applied to the etiology of many of the most common diseases seen in the neonatal
      period. Finally, the current research addressing clinical strategies in this area
      is critically appraised. Implications for practice and directions for further
      research are presented with an emphasis on strategies that support the prudent
      use of oxygen therapies.

PMID- 18827515
TI  - Examination of the newborn with congenital scoliosis: focus on the physical.
AB  - Although scoliosis at birth is rare, conditions at birth and in the newborn
      period predispose newborns to the development of scoliosis in later life.
      Scoliosis is congenital when associated with abnormal vertebral segmentation
      regardless of the age of diagnosis. Other conditions may predispose neonates to
      vertebral damage or the development of sustained uneven forces on the developing
      spine. Although it is difficult to know which newborns will progress to
      developing scoliosis, it is important to be aware of risk factors to provide
      anticipatory education for parents and to arrange appropriate follow-up after
      discharge. This article reviews the embryology of vertebral formation and risk
      factors for the development of scoliosis. The discussion includes the incidence,
      risk factors, genetics, associated problems, physical examination, and nursing
      implications of the infant with congenital scoliosis.

PMID- 18827517
TI  - Assessing the feasibility and acceptability of an intervention to reduce anxiety
      and enhance sensitivity among mothers of very low birth-weight infants.
AB  - PURPOSE: A pilot study was conducted to assess the feasibility and acceptability
      of an intervention program for mothers of very low birth-weight infants in the
      neonatal intensive care unit (NICU). SUBJECTS: Thirty-three mothers of infants
      born weighing less than 1500 g. DESIGN: A single-group, pretest-posttest design
      was used. METHODS: Preintervention mothers completed self-report questionnaires
      and their interaction with their infant was observed. Mothers then received the
      intervention program. Mothers were assessed twice postintervention, first when
      the infant was 1/2 months old and again at 6 months. At the postintervention
      assessments, mothers completed the same questionnaires and interaction was
      observed. MAIN OUTCOME MEASURES: Mothers completed the State-Trait Anxiety
      Inventory, the revised Parental Stress Scale: Neonatal Intensive Care Unit, the
      NICU Parental Beliefs Scale, and the Perinatal PTSD Questionnaire. Interactions
      between mothers and infants were rated by trained research staff using the Index
      of Parental Behaviour in the NICU. Postintervention mothers also responded to a
      questionnaire that assessed their perceptions of the intervention program.
      RESULTS: It was feasible to enroll mothers because 62% of eligible mothers agreed
      to participate. However, 39% of mothers who enrolled withdrew. Most of the
      mothers who withdrew did so before even beginning the intervention, and many of
      these women were mothers of multiples. It was also feasible to provide the
      intervention because more than 80% of mothers who began the intervention received
      all 6 teaching sessions. Mothers found both the content and the format of the
      program to be acceptable. There were nonetheless several challenges in conducting
      an intervention study with mothers early in the NICU hospitalization.
      CONCLUSIONS: The results of this pilot study are encouraging. It was found to be
      both feasible and acceptable to provide the intervention program to mothers
      during the NICU hospitalization. The effectiveness of this program needs to be
      assessed in a randomized controlled trial.

PMID- 18827518
TI  - Risk factors for necrotizing enterocolitis in preterm infants: how race, gender,
      and health status contribute.
AB  - PURPOSE: To examine 5 infant characteristics and health factors that might be
      risk factors for necrotizing enterocolitis (NEC) in preterm infants. SUBJECTS:
      One hundred thirty-four preterm infants at high risk for NEC because of either
      having a birth weight of <1500 g or requiring mechanical ventilation at birth.
      DESIGN: Descriptive secondary analysis using data from a larger longitudinal
      study. METHODS: Weekly review of infants' medical record until discharge;
      demographic questionnaire completed by mothers at the time of enrollment; and
      data analysis done with logistic regression, Fischer's exact tests, and
      correlations. OUTCOME MEASURES: Total number of days the infant required
      mechanical ventilation, birth weight in grams, number of infections prior to NEC
      diagnosis, maternal race (black, white, or Asian), and infant gender were used to
      predict the development of NEC. RESULTS: Maximum likelihood estimates indicated
      that mechanical ventilation had a positive relationship with developing NEC, such
      that as the number of days of mechanical ventilation increased so did the risk of
      developing NEC. There was also a very strong positive relationship between the
      number of nosocomial infections and NEC, indicating that as the number of
      infections increased, the likelihood of developing NEC increased. Although the
      relationship between race and NEC was not significant in the logistic regression,
      the Fisher exact test showed that black preterm infants had increased incidence
      of NEC as compared with other races. This relationship was not due to
      correlations between race and mechanical ventilation or infections. No
      relationship between gender and NEC was noted. Birth weight was not significantly
      associated with NEC in the logistic regression but was correlated with NEC,
      probably because of its correlation with mechanical ventilation and number of
      infections. CONCLUSIONS: In this sample, number of infections and length of
      mechanical ventilation were the primary predictors of NEC in preterm infants. In
      addition, the frequency that black infants are diagnosed with NEC is
      significantly higher than that of other races. Knowledge of risk factors for NEC
      can allow healthcare providers to evaluate and adjust care practices for preterm
      infants who present with higher risk for NEC on the basis of empirical data.

PMID- 18827519
TI  - Don't ever let go of the thread.

PMID- 18827520
TI  - Reclaiming our 'nursing fundamentals'.

PMID- 18827521
TI  - Nursing in a time of war.

PMID- 18827522
TI  - Nursing in a time of war.

PMID- 18827523
TI  - Improvements questioned.

PMID- 18827524
TI  - A national nurse.

PMID- 18827525
TI  - Hurricane Katrina.

PMID- 18827526
TI  - Knee replacement.

PMID- 18827527
TI  - Ratio law disappoints.

PMID- 18827528
TI  - Please, don't go.

PMID- 18827530
TI  - Hospitals must address bad behavior.

PMID- 18827533
TI  - Seeking real solutions to the nursing shortage.

PMID- 18827534
TI  - Type 1 diabetes: rates of depression in mothers and children are high.

PMID- 18827535
TI  - Chest tube insertion by NPs and PAs.

PMID- 18827536
TI  - Nurses' vigilance leads to discovery of new syndrome.

PMID- 18827537
TI  - Implementing TCAB on White 10: a retreat can advance care.
AB  - This is the second in a series of articles from Massachusetts General Hospital in
      Boston describing one general medical unit's experiences with Transforming Care
      at the Bedside (TCAB). An initiative begun by the Robert Wood Johnson Foundation
      (RWJF) and the Institute for Healthcare Improvement, TCAB was developed as a way
      to improve care on medical-surgical units, patients' and family members'
      experience of care, and teamwork among care team members, and to increase nurses'
      satisfaction and retention. The TCAB philosophy engages all care leaders, but
      empowers bedside nurses to generate ideas and solutions for change. Mass General
      is one of 68 hospitals participating in a two-year TCAB initiative led by the
      American Organization of Nurse Executives and funded by a grant from the RWJF.
      For more information on TCAB, go to www.rwjf.org/pr/product.jsp?id=31512.

PMID- 18827538
TI  - Migrant farmworkers, Maine, 2007.

PMID- 18827539
TI  - Democrats, Republicans, and health care reform.

PMID- 18827540
TI  - Postcombat sexual problems.

PMID- 18827541
TI  - Lead hazards for pregnant women and children: part 1: immigrants and the poor
      shoulder most of the burden of lead exposure in this country. Part 1 of a two
      part article details how exposure happens, whom it affects, and the harm it can
      do.
AB  - Poor, urban, and immigrant populations are at far greater risk for lead exposure
      than are other groups in the United States. Children with even slightly elevated
      blood lead levels are at increased risk for significant neurobehavioral problems
      that can extend through adolescence. Research has shown that elevated blood lead
      levels in pregnant women, even those well below 10 micrograms per deciliter-the
      Centers for Disease Control and Prevention's "level of concern"-can cause
      miscarriage, premature birth, low birth weight, and subsequent developmental
      delays in their children. Despite these well-established dangers, routine
      prenatal lead screening and lead education is not a standard of care. Part 1 of
      this two-part article presents a short case example of a pregnant mother with
      lead poisoning and describes the epidemiology of lead exposure in the United
      States, the main sources of lead exposure, and the effects of lead on the
      pregnant mother and the developing fetus and child. Prevention is crucial.
      Treatment options such as chelation must be used selectively and will not reverse
      damage once it's occurred. Part 2 will describe recommendations for screening,
      education, nutrition, reducing environmental exposures, and treatment.

PMID- 18827544
TI  - Working with families of hospitalized older adults with dementia: caregivers are
      useful resources and should be part of the care team.
AB  - Families provide a considerable amount of informal care and support for older
      adults living with dementia. And when an older adult with dementia is
      hospitalized, family caregivers should be seen as important sources of
      information and included as valuable members of the health care team. This
      article describes a best-practice approach to working with families and includes
      recommendations for using the Information for the Hospital Team About a Patient
      with Memory Problems form. For a free online video demonstrating the use of this
      form, go to http://links.lww.com/A301.

PMID- 18827546
TI  - Wandering in hospitalized older adults: identifying risk is the first step in
      this approach to preventing wandering in patients with dementia.
AB  - People who have dementia are at risk for wandering away from the safety of the
      care setting and becoming lost in the community. Reported cases of people with
      dementia wandering off, even from locations such as hospitals, have become
      increasingly common. Preventing incidents in which the patient wanders away is
      critical because once a person with dementia becomes lost, she or he may die
      before being found. Three critical elements of prevention and action are accurate
      assessment of at-risk individuals, provision of intensive supervision, and
      implementation of a standardized search plan if a person with dementia is
      missing. Watch a free video demonstrating the best practices for preventing
      hospitalized patients with dementia from wandering away at
      http://links.lww.com/A306.

PMID- 18827550
TI  - Minimally interrupted cardiac resuscitation.

PMID- 18827551
TI  - Evidence-based practice: then and now.

PMID- 18827554
TI  - Turn your presentation into a published manuscript.

PMID- 18827555
TI  - The third way: ECT isn't what it used to be.

PMID- 18827558
TI  - Agents from amphibians with anticancer properties.
AB  - Amphibians have been found to be a source of agents with anticancer properties.
      Bufalin, for example, is an anticancer agent that may induce apoptosis by its
      interaction with other genes and cellular components. Certain peptides with
      anticancer activities have been found in amphibian skin; they include magainins,
      aureins, citropin 1.1 and gaegurins. These peptides may exert a cytotoxic effect
      on human cancer cells through various mechanisms. Onconase, amphinase, cSBL
      (sialic acid-binding lectin purified from Rana catesbeiana eggs) and jSBL (sialic
      acid-binding lectin purified from Rana japonica eggs), which belong to the RNase
      A family, were purified from the oocyte cells and eggs of three amphibians, and
      they induce cytotoxicity by degrading cellular RNA. This paper discusses the
      medical and pharmaceutical significance of products derived from amphibians.

PMID- 18827559
TI  - From the podium to the patient: bringing the 2008 ASCO meeting to the clinic.
AB  - Around 4,800 abstracts on preclinical and clinical research in different oncology
      areas were presented and discussed by oncology clinicians and scientists at the
      44th American Society of Clinical Oncology meeting, the largest international
      forum in the field. As expected, the meeting provided valuable insights into
      future developments as well as enlightening clinicians regarding current
      controversies. This manuscript is an opinion-based review of the studies
      presented at the meeting, focusing on findings from randomized phase III trials
      and translational researches that, in the authors' opinion, are most likely to
      modify clinical practice or help scientists in designing future translational and
      clinical studies.

PMID- 18827560
TI  - Galloyl cyclic-imide derivative CH1104I inhibits tumor invasion through
      suppressing matrix metalloproteinase activity.
AB  - Matrix metalloproteinase (MMP)-2 and MMP-9 have been associated with the ability
      of tumor cells to metastasize because of their capacity to degrade type IV
      collagen, the main component of basement membrane, and to their elevated
      expression in malignant tumors. (S)-methyl 6-(benzyloxycarbonylamino)-2-(2-((S)
      2,6-dioxo-3-(3,4,5-trimethoxybenzamido) piperidin-1-yl) acetamido) hexanoate
      (CH1104I) is a galloyl cyclic-imide derivative designed to fit and extend into
      the S1' active pocket of MMP-2 and MMP-9. We aimed to evaluate the efficacy of
      CH1104I as a candidate compound for antiinvasion and antimetastasis of tumor
      cells. CH1104I significantly blocked gelatinase activity as evidenced by a
      decrease in the degradation of succinylated gelatin. Gelatin zymography analysis
      showed that the compound (7-210 micromol/l) inhibited the activity of MMP-2 and
      MMP-9 produced by human ovarian carcinoma SKOV3 cells. Inhibition of MMP-2 and
      MMP-9 expression was also observed using the assays of immunocytochemical
      staining and western blot analysis. The results showed that CH1104I suppressed
      the expression of zymogens and active MMP-2 and MMP-9. The effects of CH1104I on
      the invasion and migration of SKOV3 cells were then measured. Both the trans-well
      motility assay and wound scratch assay indicated that CH1104I was very effective
      for the antiinvasion and antimigration of SKOV3 cells. Furthermore, the Lewis
      lung carcinoma model was used to evaluate the efficacy of CH1104I in vivo. A
      significant inhibition of pulmonary metastasis of carcinoma cells was observed in
      CH1104I-administrated mice (25-100 mg/kg). These results suggest that CH1104I is
      a potential MMP-2 and MMP-9 inhibitor that may effectively suppress tumor
      invasion and metastasis.

PMID- 18827561
TI  - ApoG2 inhibits antiapoptotic Bcl-2 family proteins and induces mitochondria
      dependent apoptosis in human lymphoma U937 cells.
AB  - Lymphoma is one of the most common types of hematological malignancies and
      proteins from the Bcl-2 family are highly expressed in human lymphomas.
      Apogossypolone (ApoG2), the most potent gossypol derivative, has been classified
      as a novel small-molecule inhibitor of antiapoptotic Bcl-2 family proteins. Here,
      we assessed the in-vitro cytotoxicity of ApoG2 on human U937 lymphoma cells, and
      explored the underlying intracellular molecular mechanisms of ApoG2. Using the
      WST-8 assay, we found that ApoG2 inhibited growth of U937 cells in a dose
      dependent and time-dependent manner, and the IC50 values were 30.08, 14.81, and
      9.26 mumol/l for 24, 48, and 72 h treatments, respectively. ApoG2 also induced
      apoptosis in U937 cells, as noted through changes in morphological
      characteristics, including cellular internucleosomal DNA fragmentation and the
      appearance of a sub-G1 apoptotic peak. Treatment with ApoG2 downregulated Bcl-xL
      and Mcl-1 protein expression and blocked the binding of Bcl-2 with Bax protein.
      Furthermore, ApoG2 led to an abundant release of cytochrome c from mitochondria
      and a five-fold increase in the activity of caspase-3 and caspase-9. Taken
      together, our results suggest that ApoG2 could effectively suppress the growth of
      human lymphoma cell line U937 through the inhibition of the antiapoptotic Bcl-2
      family proteins and the induction of mitochondria-dependent apoptotic cell death.

PMID- 18827562
TI  - Modulation of reactive oxygen species by antioxidants in chronic myeloid leukemia
      cells enhances imatinib sensitivity through survivin downregulation.
AB  - Survivin, a member of the inhibitor of apoptosis protein family and a target for
      new drugs, is modulated by reactive oxygen species in several types of neoplasms
      including leukemias. The aim of this study is to find mechanisms to enhance
      sensitivity to imatinib in imatinib-responsive cells. In this study, we
      demonstrated through fluorescein isothiocyanate-labeled annexin V for apoptotic
      cells detection and western blotting that by inhibiting catalase activity,
      imatinib apoptosis induction was significantly enhanced (P<0.05) through
      diminishing survivin expression in K562 cells. These findings might be of
      clinical relevance and might help improve the chemotherapeutic use of imatinib
      mesylate.

PMID- 18827563
TI  - Activity of lipoplatin in tumor and in normal cells in vitro.
AB  - Lipoplatin is a novel liposomal cisplatin formulation with reduced adverse side
      effects compared with its parental compound, cisplatin. The aims of this
      preclinical study were to compare lipoplatin and cisplatin cytotoxicity in vitro
      in established cell lines derived from non-small cell lung cancer, renal cell
      carcinoma, and in normal hematopoietic cell precursors, and to identify
      biological markers associated with sensitivity and resistance. Our results showed
      a superior cytotoxicity in all tumor cell models and a much lower toxicity in
      normal cells for lipoplatin compared with cisplatin, suggesting a higher
      therapeutic index for the liposomal compound. Moreover, RT-PCR analysis of
      molecular markers known to be related to cisplatin resistance showed a direct
      correlation between cisplatin and lipoplatin resistance and ERCC1 and LRP
      expression. In conclusion, lipoplatin showed a higher antitumor activity in both
      tumor histotypes investigated and was found to be safer than the parent compound,
      cisplatin. Moreover, ERCC1 and LRP expression levels would seem to be valid
      predictors of sensitivity or resistance to these drugs.

PMID- 18827564
TI  - Interest of liposomal doxorubicin as a radiosensitizer in malignant glioma
      xenografts.
AB  - Malignant glioma patients have a life expectancy reduced to about 15 months
      despite aggressive surgery, radiotherapy (RT), and chemotherapy. Doxorubicin has
      shown a marked cytotoxic effect against malignant glioma cells in vitro. The
      brain exposure to this drug is, however, hindered by the blood-brain barrier.
      Encapsulation of doxorubicin in liposomal carriers has been shown to reduce
      toxicities and to improve brain tumors exposure to doxorubicin. In this study, we
      evaluated the radiosensitizing properties of a nonpegylated liposomal doxorubicin
      (Myocet, MYO) on two subcutaneous (U87 and TCG4) and one intracranial (U87)
      malignant glioma models xenografted on nude mice. Doxorubicin biodistribution was
      assessed by a high-performance liquid chromatography method. Antitumor efficacy
      was investigated by tumor volume measurements and mice survival determination. We
      showed that (i) encapsulation of doxorubicin ensured a preferential deposition of
      doxorubicin in tumoral tissue in comparison with free doxorubicin; (ii)
      doxorubicin accumulated in both subcutaneous and intracranial tumors during
      repeated injections of MYO and this accumulation was linked to the potentiation
      of RT efficacy on two subcutaneous models; (iii) MYO was unable to improve the
      antitumoral efficacy of RT on an intracranial glioma model. Finally, this study
      emphasizes the importance of performing preclinical studies on models closer as
      possible of human tumors and localization to be more predictive of therapeutic
      effects observed in humans.

PMID- 18827565
TI  - Squalenoyl nanomedicine of gemcitabine is more potent after oral administration
      in leukemia-bearing rats: study of mechanisms.
AB  - In an earlier report, we demonstrated the superior anticancer efficacy of orally
      administered squalenoyl gemcitabine (SQdFdC) nanomedicine over its parent drug
      gemcitabine on rats bearing RNK-16 large granular lymphocytic (LGL) leukemia. In
      the present communication, we investigated the mechanisms behind this observation
      both at the cell and tissue level. The mechanisms were investigated by performing
      cytotoxicity, cell uptake, and biodistribution experiments. In the presence of
      cytidine deaminase, SQdFdC nanoassemblies resisted deamination and exerted
      significant anticancer activity in vitro against RNK-16 LGL leukemia cells,
      whereas the cytotoxicity of free gemcitabine decreased by approximately 83-fold,
      indicating its degradation due to deamination. Additionally, the SQdFdC showed
      considerably higher intracellular accumulation and retention compared with
      gemcitabine (P<0.05). Unlike gemcitabine, the cellular access to SQdFdC was not
      influenced by nucleoside transporters. When administered orally to rats, unlike H
      gemcitabine, the H-SQdFdC absorbed slowly, but exhibited an improved
      pharmacokinetics and tissue distribution profile, particularly in the lymphoid
      organs (the major organs of metastasis). The resistance to deamination, followed
      by the improved pharmacokinetic and tissue distribution, and greater accumulation
      and retention at the level of cancer cells, are the key factors for the
      superiority of SQdFdC nanoassemblies over free gemcitabine against RNK-16 LGL
      leukemia in rats.

PMID- 18827566
TI  - Reducing anti-DT IgG concentrations to improve the efficacy of a diphtheria
      fusion protein.
AB  - Preformed antidiphtheria toxin (anti-DT) IgG limits the development of diphtheria
      fusion proteins because the anti-DT IgG binds and removes the diphtheria fusion
      protein from the circulation. In our phase I trial of DT-granulocyte macrophage
      colony stimulating factor (GMCSF), a truncated DT linked to human GMCSF, in
      relapsed or refractory acute myeloid leukemia, patients with high concentrations
      of preexisting anti-DT IgG (>2.5 microg/ml) had significantly lower DT-GMCSF
      concentrations. This study details the fate of anti-DT IgG during the patient's
      treatment with DT-GMCSF and describes how we could lower anti-DT IgG
      concentrations and increase the patient's exposure to DT-GMCSF. Using an enzyme
      immunoassay, we measured anti-DT IgG concentrations before the first cycle of
      treatment (baseline) and on day 2 (after one dose of DT-GMCSF) and on day 5
      (after four doses of DT-GMCSF). Thirty-three patients with relapsed or refractory
      acute myeloid leukemia in the phase 1 trial received DT-GMCSF at doses from 1 to
      5 microg/kg/day intravenously for 5 days. The mean anti-DT IgG concentration
      pretherapy was 1.3 microg/ml (range: undetectable to 7.8) and significantly
      decreased to a mean concentration of 0.7 microg/ml on day 2 (P=0.007) and to 0.5
      microg/ml on day 5 (P<0.0001). In two individuals in whom we measured DT-GMCSF
      concentrations on day 1 and day 5, we observed that a decrease in anti-DT IgG
      concentrations was associated with an increase in DT-GMCSF concentrations. No
      relationship was observed between dose of DT-GMCSF and the absolute change in
      anti-DT IgG concentrations on day 2 (r=-0.01, P=0.98) or day 5 (r=-0.12, P=0.53).
      For patients with high baseline anti-DT IgG concentrations, a single dose of DT
      GMCSF could be used to lower the anti-DT IgG concentrations and potentially
      result in a significant increase in DT-GMCSF concentrations and efficacy.

PMID- 18827568
TI  - Targeting the mammalian target of rapamycin in myxoid chondrosarcoma.
AB  - Myxoid chondrosarcoma is a slow-growing sarcoma poorly responsive to chemotherapy
      and radiation therapy. Translational research has validated several proteins as
      optional therapeutic targets. Significant responses are, however, rare. In this
      paper we report an extraordinary response of myxoid chondrosarcoma to targeted
      therapy by rapamycin in combination with cyclophosphamide. Our case points to a
      possible novel therapeutic approach towards myxoid chondrosarcoma, by targeting
      the mammalian target of rapamycin protein, and probably protein kinase C-alpha,
      mitogen-activated protein kinase, and Jun N-terminal kinase too, by rapamycin.

PMID- 18827567
TI  - Docetaxel plus oxaliplatin (DOCOX) as a second-line treatment after failure of
      fluoropyrimidine and platinum in Chinese patients with advanced gastric cancer.
AB  - The fluoropyrimidine and platinum-based combination chemotherapy is now widely
      used as first-line therapy for advanced gastric cancer (AGC). Unfortunately,
      about half of all patients do not respond to the current first-line chemotherapy
      and furthermore, most patients who achieve response to first-line chemotherapy
      eventually experience disease progression. Although there is a need for effective
      salvage treatment after the failure of first-line chemotherapy, data on the
      safety and efficacy of second-line treatment in AGC is limited. The current study
      evaluated an experimental combination regimen of docetaxel (60 mg/m) as an
      intravenous infusion of less than 1 h, followed by oxaliplatin (130 mg/m)
      intravenously for less than 2 h. Both drugs were administered on day 1 of a 21
      day cycle, in pretreated Chinese patients with AGC. The trial enrolled 48
      patients of whom 46 (95.8%) were assessable for response. The median time to
      progression was 4.4 months (95% confidence interval (CI): 3.4-5.4 months) and the
      median overall survival was 7.2 months (95% CI: 6.6-12.1 months). Partial
      response was confirmed in 11 of 48 cases (22.9%; 95% CI: 10.9-34.9%) and no
      complete responses were seen. Significant hematologic toxicity was noted with
      grade 3 and grade 4 neutropenia occurring in 21.7 and 4.3% of patients,
      respectively, as well as grade 3 thrombocytopenia occurring in 4.3% of patients.
      Grade 3 febrile neutropenia occurred in 6.5% of the patients. There were no
      treatment-related deaths during on the study. In summary, docetaxel and
      oxaliplatin have modest activity with predictable hematologic toxicity when given
      as salvage therapy for Chinese patients treated earlier for AGC. Given the short
      duration of response more focus should be given to newer biologic agents and
      triplet regimens.

PMID- 18827570
TI  - Human brain evolution: food for thoughts.

PMID- 18827571
TI  - Caloric restriction and brain function.
AB  - PURPOSE OF REVIEW: In addition to extending lifespan, animal research shows that
      specific diets benefit brain functioning. Indeed, it has been proven that caloric
      restriction prevents age-related neuronal damage. What are those mechanisms
      involved in the effects of caloric restriction on brain functioning? Could
      caloric restriction be proposed in the future to prevent or treat
      neurodegenerative disorders such as Alzheimer's disease? Is there a future for
      caloric restriction interventions in adults? RECENT FINDINGS: Hypotheses linking
      caloric restriction to cognitive capability include anti-inflammatory mechanisms,
      reduction of neural oxidative stress, promotion of synaptic plasticity, induction
      of various stress and neurotrophic/neuroprotective factors. Caloric restriction
      may also prevent beta-amyloid neuropathology in Alzheimer transgenic models.
      Finally, both exercise and caloric restriction enhance neurogenesis via different
      mechanisms suggesting that their combination may decrease the risk of
      neurodegenerative disease. SUMMARY: It is now well established that caloric
      restriction could be used to promote successful brain aging. Data from randomized
      controlled trials in humans are limited. No positive effect on cognitive
      impairment was found probably due to methodological limitations. The long-term
      effects of caloric restriction in adults must be clarified before engaging in
      such preventive strategy. Additional animal studies must be conducted in the
      future to test the effects of 'multidomain' interventions (caloric restriction
      plus regular exercise) on age-related cognitive decline.

PMID- 18827573
TI  - Food ingredients and cognitive performance.
AB  - PURPOSE OF REVIEW: To integrate recent discoveries in the cognitive neuroscience
      field on overall brain development, performance and energy requirements, with
      insight obtained on the cellular and molecular mechanisms of stimulation with
      food at the periphery. RECENT FINDINGS: A clear picture emerges of the brain
      energy demand, its changes through life and the nutritional requirements to
      provide an optimally functioning intellect at any time. Of particular importance
      is the dynamic range resulting from differences between 'poor diet' and 'optimal
      diet'. On the basis of a healthy brain, the question becomes: what drives
      transient cognitive performance, and to what extent does food-related input from
      the periphery modulate cognition in general? Over the last decade, vast
      achievements in the understanding of chemosensory signal transduction on the
      tongue have been made. Most molecular receptors for various taste modalities have
      been identified, and the logic of their coding into the brain has been largely
      unravelled. Moreover, an intriguing discovery has been made that most of the
      known taste receptors are also expressed in the gastrointestinal tract. SUMMARY:
      Brain energy supply and balanced diet are being unravelled on the molecular and
      cellular levels as prerequisites for proper cognitive development. With
      additional insight emerging into the fundamentals of sensory stimulation and
      perception, we are entering a scientific era that ultimately will link metabolic
      needs with food preferences, hedonics and healthy nutrition.

PMID- 18827574
TI  - Zinc and diarrheal disease: current status and future perspectives.
AB  - PURPOSE OF REVIEW: To evaluate clinical data indicating the benefits of oral zinc
      supplementation to prevent and/or treat diarrhea in children and extend these
      findings to adults. RECENT FINDINGS: Zinc plays an important role in modulating
      host resistance to infectious agents and reducing the risk, severity, and
      duration of diarrheal diseases. Zinc is important in the developing world and in
      low-income and middle-income countries where mild-to-moderate zinc deficiency is
      highly prevalent.The WHO/UNICEF recommendations for zinc supplementation are
      based on meta-analyses of randomized, controlled intervention trials on children:
      20 mg zinc/day for 10-14 days for children with acute diarrhea and 10 mg/day for
      infants under 6 months of age. Effective forms include sulfate, gluconate, or
      acetate. No similar studies have been conducted on adults. Thus, carefully
      conducted clinical trials are necessary to ascertain the efficacy of zinc in
      prevention of acute and persistent diarrhea in adults. SUMMARY: Faced with rising
      antibiotic resistance and the lack of effective antidiarrheal vaccines, oral zinc
      provides substantial benefit in the reduction of stool output and disease
      duration combined with safety, selectivity of action, and low cost. Thus, oral
      zinc supplementation is a practical therapeutic intervention for the treatment of
      diarrhea in children, and by extension, should be provided to adults.

PMID- 18827572
TI  - Sarcopenic obesity: definition, cause and consequences.
AB  - PURPOSE OF REVIEW: Older obese persons with decreased muscle mass or strength are
      at special risk for adverse outcomes. We discuss potential pathways to muscle
      impairment in obese individuals and the consequences that joint obesity and
      muscle impairment may have on health and disability. Tantamount to this
      discussion is whether low muscle mass or, rather, muscle weakness should be used
      for the definition. RECENT FINDINGS: Excess energy intake, physical inactivity,
      low-grade inflammation, insulin resistance and changes in hormonal milieu may
      lead to the development of so-called 'sarcopenic obesity'. It was originally
      believed that the culprit of age-related muscle weakness was a reduction in
      muscle mass, but it is now clear that changes in muscle composition and quality
      are predominant. We propose that the risk of adverse outcomes, such as functional
      limitation and mortality, is better estimated by considering jointly obesity and
      muscle strength rather than obesity and muscle mass and the term 'sarcopenic
      obesity' should be revisited. SUMMARY: Recognition of obese patients who have
      associated muscle problems is an essential goal for clinicians. Further research
      is needed to identify new target for prevention and cure of this important
      geriatric syndrome.

PMID- 18827575
TI  - Selenium and anticarcinogenesis: underlying mechanisms.
AB  - PURPOSE OF REVIEW: To discuss recent research related to anticarcinogenic
      mechanisms of selenium action in light of the underlying chemical/biochemical
      functions of the selenium species, likely to be executors of those effects.
      RECENT FINDINGS: Recent studies in a variety of model systems have increased the
      understanding of the anticarcinogenic mechanisms of selenium compounds. These
      include effects on gene expression, DNA damage and repair, signaling pathways,
      regulation of cell cycle and apoptosis, metastasis and angiogenesis. These
      effects would appear to be related to the production of reactive oxygen species
      produced by the redox cycling, modification of protein-thiols and methionine
      mimicry. Three principle selenium metabolites appear to execute these effects:
      hydrogen selenide, methylselenol and selenomethionine. The fact that various
      selenium compounds can be metabolized to one or more of these species but differ
      in anticarcinogenic activity indicates competing pathways of their metabolic and
      chemical/biochemical disposition. Increasing knowledge of selenoprotein
      polymorphisms has shown that at least some are related to cancer risk and may
      affect carcinogenesis indirectly by influencing selenium metabolism. SUMMARY: The
      anticarcinogenic effects of selenium compounds constitute intermediate mechanisms
      with several underlying chemical/biochemical mechanisms such as redox cycling,
      alteration of protein-thiol redox status and methionine mimicry.

PMID- 18827576
TI  - The risks of free copper in the body and the development of useful anticopper
      drugs.
AB  - PURPOSE OF REVIEW: To review the toxicity and risks of free copper in Wilson's
      disease, Alzheimer's disease, other disease of neurodegeneration, and cognitive
      loss in the general population. We will also review the anticopper drugs and how
      lowering free copper levels with an anticopper drug inhibits fibrosis,
      inflammation, and autoimmunity. RECENT FINDINGS: Some exciting recent work
      indicates that free copper levels are increased in Alzheimer's disease, and
      copper may be involved in disease pathogenesis, opening the way to possible
      therapy of Alzheimer's disease with anticopper drugs. Copper may also be involved
      in other diseases of neurodegeneration. A very exciting recent study indicts high
      intake of copper, mostly from copper supplements, in conjunction with a high-fat
      diet in more rapid cognitive decline in the general population. Other data
      indicate that even low levels of copper in drinking water, perhaps similar to
      copper supplements, bypasses the liver, enters the circulation, increases the
      blood-brain penetration of copper, and may cause damage. SUMMARY: Some of the
      implications are that Alzheimer's disease and other diseases of neurodegeneration
      and fibrotic, inflammatory, and autoimmune diseases may be treatable by lowering
      the availability of free copper. People in the general population may wish to
      take steps to lower their free copper levels and, in particular, to abstain from
      taking copper supplements and ingesting significant amounts of copper in drinking
      water.

PMID- 18827577
TI  - Quercetin: potentials in the prevention and therapy of disease.
AB  - PURPOSE OF REVIEW: Quercetin is discussed since several decades as a multipotent
      bioflavonoid with great potential for the prevention and treatment of disease. In
      the current review, we present the most recent findings on quercetin with regard
      to the pharmacology, the in-vitro and in-vivo effects in different cell systems
      and animal models, and the clinical effects in humans. RECENT FINDINGS: Quercetin
      bioavailability has been underestimated in the past and can be improved by food
      matrix components or particular delivery forms. Among the biological effects of
      particular relevance, the antihypertensive effects of quercetin in humans and the
      improvement of endothelial function should be emphasized. Together with its
      antithrombotic and anti-inflammatory effects, the latter mainly mediated through
      the inhibition of cytokines and nitric oxide, quercetin is a candidate for
      preventing obesity-related diseases. Most exiting are the findings that quercetin
      enhances physical power by yet unclear mechanisms. The anti-infectious and
      immunomodulatory activities of quercetin might be related to this effect.
      SUMMARY: Quercetin is a most promising compound for disease prevention and
      therapy; however, many of the effects still need confirmation by human
      intervention trials.

PMID- 18827578
TI  - Parenteral ascorbic acid in haemodialysis patients.
AB  - PURPOSE OF REVIEW: Parenteral ascorbic acid has been frequently used to overcome
      problems of vitamin C deficiency in haemodialysis patients. The benefits of
      vitamin C supplementation in clinical studies have been controversial and did not
      consider toxicological aspects. The review summarizes recent findings of the
      effects of parenteral ascorbic acid and discusses toxicological effects. RECENT
      FINDINGS: Vitamin C deficiency in haemodialysis patients, which has been
      frequently described, cannot be improved with oral supplementation due to limited
      absorption of high dosages. To avoid consequences of vitamin C deficiency,
      parenteral vitamin C solutions should be administered because this intervention
      is the only way to guarantee a sufficient supply to the cells. A beneficial
      consequence of parenteral vitamin C on the recombinant human erythropoietin
      resistance is an additional therapeutic effect, which contributes to the
      prevention of iron deficiency anaemia in haemodialysis patients. Thus, large
      amount of supplemental vitamin C are required for extended periods of time (up to
      500 mg 3 times a week). To avoid hyperoxaluria, plasma oxalate levels should be
      monitored on a regular basis, for example, once a week. SUMMARY: Parenteral
      administration of ascorbic acid may be an approach that can overcome problems of
      vitamin C deficiency in haemodialysis patients - in particular problems of iron
      overload, erythropoetin resistance, and chronic inflammation.

PMID- 18827579
TI  - Proteins and satiety: implications for weight management.
AB  - PURPOSE OF REVIEW: To highlight the satiating background and effects of proteins
      and their implications for weight management. RECENT FINDINGS: The satiating
      effect of protein is the key player in body-weight loss and body-weight
      maintenance thereafter. Specific high-protein meals or high-protein diets induced
      satiety require a realistic bandwidth of energy intake, protein concentrations,
      texture, and timing of assessment of effects. Satiety is nutrient specifically
      supported by elevated amino acid concentrations, responses of anorexigenic
      hormones or protein-induced energy expenditure. During long-term high-protein
      diets sustained satiety, energy expenditure, and sparing fat-free body mass are
      essential. For effects due to satiety, ad libitum energy intake conditions are
      necessary. Adverse events related to kidney damage may occur with sulphur
      containing amino acids; individuals with obesity, metabolic syndrome and diabetes
      mellitus II may be susceptible groups. SUMMARY: Highly controlled medium-term
      studies overcoming possible differences due to texture, timing and macronutrient
      exchange, and assessing satiety, energy expenditure and substrate oxidation at
      the same time, need to be executed with a realistic bandwidth of different types
      of proteins in overweight individuals in different energy balances.

PMID- 18827580
TI  - Vitamin D in the prevention and treatment of coronary heart disease.
AB  - PURPOSE OF REVIEW: The pathogenesis of coronary heart disease is of
      multifactorial origin. Probably, not all risk factors are satisfactorily
      understood. This article outlines beneficial vitamin D effects on cardiac
      function and the vasculature. In addition, human data associating serum vitamin D
      metabolite levels or oral vitamin D dosages or both with coronary heart disease
      outcome parameters are reviewed. RECENT FINDINGS: There is accumulating evidence
      that the vitamin D hormone calcitriol exerts important physiological effects in
      cardiomyocytes, vascular smooth muscle cells, and the vascular endothelium. Low
      levels of the calcitriol precursor 25-hydoxyvitamin D are associated with
      myocardial infarction, congestive heart failure, and calcific aortic stenosis.
      Deficient calcitriol concentrations probably contribute to the massive vascular
      calcification seen in chronic kidney disease. In patients with end-stage renal
      disease and end-stage heart failure, very low-circulating calcitriol levels or
      nonuse of active vitamin D or both are independently associated with high
      mortality rates. SUMMARY: Despite these exciting data, it is still too early to
      recommend exact dosages for the prevention or therapy of coronary heart disease.
      Prospective, randomized controlled trials with different amounts of vitamin D and
      probably with its active form calcitriol are needed to determine whether vitamin
      D can prevent coronary heart disease events and mortality.

PMID- 18827581
TI  - Green tea and cardiovascular disease: from molecular targets towards human
      health.
AB  - PURPOSE OF REVIEW: To summarize current knowledge of the protective effects of
      green tea and green tea constituents, particularly catechins, on the
      cardiovascular system. RECENT FINDINGS: Consumption of green tea has been
      inversely associated with the development and progression of cardiovascular
      diseases and cardiovascular risk factors. Mechanisms that have been suggested as
      being involved in the antiatherosclerotic effects of green tea consumption
      primarily entail antioxidative, antiinflammatory, antiproliferative, and
      antithrombotic properties, as well as beneficial effects on endothelial function.
      Moreover, evidence exists for myocardial effects of tea constituents, including
      positive inotropic and antihypertrophic effects, and beneficial impact in
      myocardial ischaemia-reperfusion injury. SUMMARY: Green tea represents a
      promising tool for the prevention of cardiovascular disorders.

PMID- 18827582
TI  - Nonalcoholic fatty liver disease: the potential role of nutritional management.
AB  - PURPOSE OF REVIEW: To review available data pertaining to dietary imbalances and
      metabolic alterations leading to the development of fatty liver disease and
      nutritional managements. RECENT FINDINGS: The importance of treating fatty liver
      disease is now firmly recognized not only because of the risk of progression
      toward a more aggressive liver disease but also because the fatty liver is an
      important provider of cardiovascular risks. The ideal diet for nonalcoholic fatty
      liver disease/nonalcoholic steatohepatitis patients should reduce fat mass and
      inflammation in the adipose tissue, restore insulin sensitivity, and provide low
      amounts of substrates for de-novo lipogenesis, but scientific evidence to
      recommend specific diets is currently lacking. Moderate weight loss, low-calorie
      diets, reduction in saturated fatty acids intake, together with an increase in
      monosaturated and n-3 polyunsaturated fatty acids appear to be beneficial.
      Excessive consumption of high glycemic index carbohydrates appears deleterious,
      as it favors hyperglycemia and hyperinsulinemia and stimulates de-novo
      lipogenesis. Physical exercise is an important component of the approach, as it
      improves insulin sensitivity. Behavioral therapy promotes long-term compliance to
      lifestyle modifications. SUMMARY: One panacea is unlikely to be found, the more
      useful approach is probably multimodal and includes tailored lifestyle
      modifications. Randomized controlled trials are needed to establish dietary
      recommendations. While awaiting such trials, reduced consumption of simple sugar,
      especially sweetened beverages, and incremental increase in physical activity
      must be encouraged.

PMID- 18827583
TI  - Functional food for exercise performance: fact or foe?
AB  - PURPOSE OF REVIEW: To present food components showing evidence for improved sport
      performance in the light of the scientific literature from the past 2 years.
      RECENT FINDINGS: Appropriate nutrition is essential for sport performance.
      Nutritional products containing carbohydrates, proteins, vitamins, and minerals
      have been widely used by athletes to provide something extra to the daily
      allowance. Currently, the field of interest is shifting from macronutrients and
      fluids to physiologically active isolated food components. Several of them have
      been demonstrated to improve sport performance at a higher level than expected
      with a well balanced diet. In the present review, we will focus on the benefits
      of creatine, caffeine, branched-chain amino acids, and more particularly leucine,
      beta-alanine, bicarbonate, and glycerol ingestion on exercise performance.
      SUMMARY: A bulk of products are sold on the market labeled with various
      performance benefit statements without any scientific evidence. These food
      components are often used without a full understanding or evaluation of the
      potential benefits and risks associated with their use. There is thus a real need
      to classify food components on the basis of their evidence-based effectiveness.

PMID- 18827584
TI  - The role of prebiotics and synbiotics in critically ill patients.
AB  - PURPOSE OF REVIEW: To examine current knowledge regarding the role of prebiotics
      in critical illness when administered singly or in combinations with probiotics
      (synbiotics). RECENT FINDINGS: Recent experimental and clinical studies support
      the fact that bioecological intestinal control with early enteral nutrition
      enriched with synbiotics may reduce systemic inflammation, improve the
      immunological status of the intestinal mucosa and help prevent infections in
      critically ill patients. Three prebiotics, oligofructose, galactooligosaccharides
      and lactulose are able to modify the balance of intestinal microbiota. It appears
      that treatment with synbiotics during critical illness should restore the balance
      of microbial communities in a beneficial way with positive effects on intestinal
      permeability and bacterial translocation. Only data from small trials are
      currently available to support use of prebiotics and synbiotics in the treatment
      of different clinical scenarios. However, in some critical conditions, this
      supplementation has so far not been effective. SUMMARY: Numerous questions about
      the molecular mechanisms of action or clinical indications of prebiotics remain
      unanswered. Large, randomized, multicentre trials are necessary to precisely
      define the role of prebiotics as therapeutic agents in critical illness. These
      trials must identify clinically significant improvements in relevant clinical
      endpoints before any large-scale usage is advocated for critical illness.

PMID- 18827586
TI  - Current world literature. Nutrition and physiological function.

PMID- 18827585
TI  - The impact of music on hypermetabolism in critical illness.
AB  - PURPOSE OF REVIEW: Although the literature on complementary therapy, including
      music, is vast, there are few studies conducted in a scientific fashion exploring
      physiologic mechanisms. This review summarizes recent evidence on the effects of
      music on the hypermetabolic response of critical illness. RECENT FINDINGS: Music
      may restore some of the distorted homeostasis observed in ICU patients, as well
      as reducing pain and the need for sedation. Music likely reduces alterations in
      the hypothalamic-anterior pituitary-peripheral hormone axes that produce cortisol
      and growth hormone. Music may also increase growth hormone levels, which can
      induce decreased production of cytokines such as IL-6 by white blood cells.
      Further, ovarian steroid secretion may paradoxically protect women by increasing
      baseline circulating stress hormones, providing an opportunity for music therapy
      to intervene effectively. Dopaminergic neurotransmission has been implicated as a
      means by which music can modulate the central nervous system. SUMMARY: Music may
      play an important role as an adjunct therapy in critical care. However, further
      studies are necessary to elucidate how music can be further integrated clinically
      and the precise underlying mechanisms of its beneficial effects.

PMID- 18827587
TI  - Complications of acetabular fracture surgery in morbidly obese patients.
AB  - OBJECTIVES: To compare the early complications with operative treatment of
      acetabular fractures in morbidly obese (body mass index >or=40) patients when
      compared with all other patients. DESIGN: Retrospective review. SETTING:
      University medical center. PATIENTS/PARTICIPANTS: Four hundred thirty-five
      consecutive patients with acetabular fractures operatively treated by a single
      surgeon. Forty-one of these patients were morbidly obese (group 1) and were
      compared with the remaining patients (group 2). Group 2, therefore, included
      patients who were clinically overweight and obese. INTERVENTION: Operative repair
      of acetabular fracture. MAIN OUTCOME MEASUREMENTS: Outcome variables included
      patient positioning time, total operative time, estimated intraoperative blood
      loss, length of hospital stay, perioperative complications, and late
      complications. RESULTS: The average total operative time was 293 minutes for
      group 1 and 250 minutes (P = 0.008) for group 2. The hospital stay for group 1
      averaged 26 days versus 15 days in group 2 (P < 0.01). There were 19 (46%) wound
      complications in group 1 compared with 49 (12%) in group 2 (P < 0.0001). Overall,
      there were complications in 26 of the 41 patients (63%) in group 1 and in 96 of
      the 394 patients (24%) in group 2. Group 1's relative risk of having a
      complication was 2.6 (95% confidence interval = 2.4-2.8) when compared with group
      2. CONCLUSIONS: Our morbidly obese population had a statistically higher
      complication rate, longer operative times, and greater estimated intraoperative
      blood loss. The majority of complications were related primarily to wound healing
      problems and successfully controlled with aggressive approach to surgical
      debridement.

PMID- 18827588
TI  - Platelet-rich concentrate supports human mesenchymal stem cell proliferation,
      bone morphogenetic protein-2 messenger RNA expression, alkaline phosphatase
      activity, and bone formation in vitro: a mode of action to enhance bone repair.
AB  - OBJECTIVE: Platelet-rich concentrate (PRC) is an autologous growth factor
      preparation that is in routine use for orthopaedic and maxillofacial surgery.
      However, there are little data available describing the cellular and molecular
      mechanisms by which PRC enhances the healing response in an osseous environment.
      The aim of this study was to identify cellular and molecular events that are
      modulated in human mesenchymal stem cells (hMSCs) in response to exposure to
      human PRC generated by a novel filtration-based device (CAPTION, Smith & Nephew
      Inc). METHODS: PRC and serum were prepared from blood donated by 11 volunteers.
      Growth factor content and release from PRC were determined by enzyme-linked
      immunosorbent assay. Cell proliferation was quantified by DNA content and
      osteoblastic differentiation by alkaline phosphatase expression and mineralized
      nodule formation. Real-time reverse transcription-polymerase chain reaction
      analysis was used to determine the early molecular pathways regulated in hMSCs by
      PRC. RESULTS: The results obtained confirm previous in vitro and in vivo
      observations demonstrating that PRC enhances hMSC proliferation. Furthermore, our
      data suggest that when added as a clot, PRC induces an earlier onset of
      proliferation compared with serum without leading to cell overgrowth and the
      inhibition of cell differentiation. At the molecular level, PRC treatment
      stimulated a transient enhancement of bone morphogenetic protein-2 messenger RNA
      that peaked after 12 hours and induced an earlier and a sustained increase in the
      key osteogenic transcription factor RUNX2. By 3 days of treatment, PRC enhanced
      alkaline phosphatase activity more than 2-fold compared with donor-matched serum,
      and at 23 days, the increase in osteoblastic commitment translated to enhanced
      calcified matrix deposition. CONCLUSIONS: Taken together, the data presented here
      suggest that treatment of hMSC with clotted PRC, in an osteoinductive
      environment, enhances osteoblastic commitment and bone formation. Furthermore,
      these data indicate that the enhanced osteogenesis seen in the presence of PRC
      cannot be explained solely by enhanced cell proliferation, suggesting that PRC
      modulates a number of cell and molecular pathways to promote bone formation.

PMID- 18827589
TI  - Does a volar locking plate provide equivalent stability as a dorsal nonlocking
      plate in a dorsally comminuted distal radius fracture?: a biomechanical study.
AB  - OBJECTIVES: The purpose of this study was to compare the fixation afforded by a
      dorsal nonlocking plate with a volar locking plate in a fracture model simulating
      an extra-articular distal radius fracture with dorsal comminution (OTA
      [Orthopaedic Trauma Association] type 23-A3.2). METHODS: In 10 matched pairs of
      fresh-frozen cadaveric arms, a comminuted extra-articular dorsally unstable
      distal radius fracture (OTA type 23-A3.2) was created. The fractures were fixed
      with either dorsally placed nonlocking T-plate or volarly placed locking plate
      within matched pairs. The precycling stiffness with axial and torsional loading
      of the specimens was determined. The specimens were then loaded axially for 5000
      cycles, and postcycling axial and torsional stiffness and load to failure were
      determined. RESULTS: The mean axial and torsional stiffness before and after
      cyclic loading of fractures stabilized with dorsal nonlocking plate was not
      significantly different than fractures fixed with volar locking plate. Although
      the mean load to failure was greater for the volar locking plate group than
      dorsal nonlocking plate group, the difference was not significant. CONCLUSIONS:
      This study suggests that the fixation obtained with volar locking plates is as
      stable as fixation with a dorsal plate in acute healing period and can withstand
      the functional demands of the immediate postoperative period in dorsally
      comminuted unstable extra-articular distal radius fractures. Elimination of
      dorsal tendinopathy by using volar locking plates may lead to fewer long-term
      complications. Locking plates provided better stability in specimens with
      osteoporosis.

PMID- 18827590
TI  - Acute vascular injury associated with fracture of the distal radius: a report of
      6 cases.
AB  - OBJECTIVES: To highlight the potential for vascular injury with fracture of the
      distal radius. DESIGN: Retrospective case series. SETTING: The practices of
      several orthopaedic hand surgeons. PATIENTS/PARTICIPANTS: Six patients with
      arterial injury as a consequence of fracture of the distal radius: 2 partial
      lacerations of the radial artery, 2 complete arterial lacerations (1 radial and 1
      ulnar), 1 thrombosed radial artery, and 1 thrombosed ulnar artery. There were 4
      men and 2 women with an average age of 42 years (range 26-70 years). Three of the
      fractures were open, and 3 had an associated distal ulnar fracture. INTERVENTION:
      Volar open reduction and internal fixation of the distal radius fracture.
      Ligation or no treatment for 3 arterial injuries and repair or vein graft
      reconstruction (1 patient) for 3 injuries. MAIN OUTCOME MEASUREMENTS: Vascular
      status of the hand. RESULTS: At an average follow-up of 9 months (range 5-16
      months), all patients had a well-vascularized hand, normal capillary refill, and
      no complaints of vascular dysfunction. CONCLUSIONS: Vascular complications, once
      thought rare in association with fracture of the distal radius, may be more
      frequently recognized as volar exposures are increasingly used. Because most
      single artery injuries in the wrist and forearm are not associated with ischemia,
      identification of these injuries is unlikely to affect the functional result or
      outcome. In the unusual patient with a dysvascular hand after distal radius
      fracture, arterial reconstruction may be necessary.

PMID- 18827591
TI  - Lateral collateral ligament repair restores the initial varus stability of the
      elbow: an in vitro biomechanical study.
AB  - OBJECTIVE: Lateral collateral ligament (LCL) repair of the elbow is commonly
      performed in the management of unstable dislocations and fracture dislocations of
      the elbow. The appropriateness of clinically employed techniques of LCL repair in
      restoring elbow kinematics and stability has not been reported. The purpose of
      this in vitro study was to evaluate the effectiveness of LCL transosseous sutures
      repair and the influence of ligament tensioning on the initial kinematics and
      stability of the elbow. METHODS: Six cadaveric upper extremities were mounted in
      a motion simulator with tracking system, which enabled both passive and simulated
      active elbow flexion while measuring the motion of the ulna relative to the
      humerus. Transosseous sutures were placed in the LCL and passed through a humeral
      bone tunnel entering at the center of curvature of the capitellum near the
      lateral epicondyle with exit holes in the lateral supracondylar ridge. With the
      arm slightly flexed, an actuator pulled on the sutures to achieve 20, 40, and 60
      N of LCL repair tension, and the sutures were then secured at that tension.
      RESULTS: Transosseous repair of the LCL restored the initial kinematics of the
      elbow at 20 N of tension. Greater magnitudes of initial repair tension in vitro
      overcorrected the varus instability causing the elbows to track in excessive
      valgus and internal rotation. CONCLUSIONS: These in vitro data suggest that LCL
      repair using transosseous sutures is a useful technique to restore the initial
      kinematics of the elbow. An LCL repair tension of 20 N or perhaps slightly less
      should be employed in clinical studies to confirm these laboratory observations.

PMID- 18827592
TI  - Polyaxial locking plate fixation in distal femur fractures: a biomechanical
      comparison.
AB  - OBJECTIVES: Uniaxial, first-generation locking plates have become increasingly
      popular for fixation of supracondylar femur fractures. Polyaxial plates are
      currently available, which allow for variable-angle screw insertion; however, the
      biomechanical integrity of these new locking constructs is yet unproven. This
      study compares the mechanical stability of a conventional locking plate with that
      of a new polyaxial design. METHODS: A comminuted supracondylar femur fracture
      (AO/OTA33-A3) gap model was created in fourth-generation synthetic composite
      bones. Fixation was obtained with 2 different plate constructs: (1) a
      conventional locking plate (uniaxial screw heads threading directly into plate)
      and (2) a polyaxial locking plate (screw heads are captured and "locked" into a
      fixed angle using locking caps). Eight specimens of each type were then tested in
      axial, torsional, and cyclic axial modes on a material testing machine. RESULTS:
      The mean axial stiffness for the polyaxial locking plate was 24.4% greater than
      the conventional locking plate (168.2 vs 127.1 N/mm; P < 0.0001). The mean
      torsional stiffness was also greater for the polyaxial plate (2.78 vs 2.57
      Nm/degree; P = 0.0226). Cyclic axial loading caused significantly less (P =
      0.0034) mean irreversible deformation in the polyaxial plate (5.6 mm) than in the
      conventional plate (8.8 mm). The mean ultimate load to failure was significantly
      higher (P = 0.0005) for the polyaxial plate (1560 N) than for the conventional
      plate (1337 N). CONCLUSIONS: The tested plate construct with its polyaxial
      locking screw mechanism provides a biomechanically sound fixation option for
      supracondylar femur fractures. The frictional locking mechanism allows
      maintenance of angular stability while affording the option of variable screw
      placement.

PMID- 18827593
TI  - Posterior fracture dislocation of the ankle: technique and clinical experience
      using a posteromedial surgical approach.
AB  - OBJECTIVE: The purpose of this study is to revisit the posteromedial surgical
      approach to the ankle and report the clinical outcomes of this technique in a
      cohort of 17 patients. DESIGN: Retrospective. SETTING: Level I trauma center.
      PATIENTS: Seventeen patients between 1990 and 2006 were treated using a
      posteromedial surgical approach to the ankle. Thirteen presented with a posterior
      ankle fracture dislocation and 4 with an ankle fracture without dislocation
      producing a large posterior malleolar fragment. There were 6 males and 11
      females, from 23 to 80 years of age (mean 45.2 years). INTERVENTION: All but 2
      patients underwent open reduction and internal fixation of the posterior
      malleolar fracture using a single posteromedial approach. A combined surgical
      approach (posteromedial and posterolateral) to the ankle was used in 2 cases.
      MAIN OUTCOME MEASUREMENTS: The Foot and Ankle Outcomes Questionnaire was used to
      evaluate postoperative ankle pain, function, stiffness and swelling, and giving
      way. Posttraumatic osteoarthritis was assessed using an adapted 4-point
      radiographic grading system. RESULTS: Follow-up data on 12 patients were obtained
      at a mean interval of 9.4 years. There were no wound complications. The average
      global foot and ankle score was 87 points (range 69-100). The degree of arthrosis
      was grades 0 in 3 ankles, I in 1 ankle, II in 5 ankles, and III in 3 ankles.
      CONCLUSIONS: The posteromedial approach offers an effective technique for
      fracture reduction and buttress plate fixation of large posterior malleolar
      fragments. Good short- and mid-term clinical results should be expected.

PMID- 18827594
TI  - The effect of cement mixing time on the biomechanics of cement augmented plated
      fractures in canine femora.
AB  - OBJECTIVE: The goal of this study was to determine the effect of cement mixing
      time and, hence, cement viscosity on the biomechanical behavior of femoral
      fracture fixation. DESIGN: Cadaveric plated canine femoral fracture model,
      comparing treatments in matched pairs. SETTING: Orthopaedic biomechanics
      laboratory. INTERVENTION: Cement was inserted both as a liquid and as a paste in
      standard and oversized screw holes to augment fixation with plates and screws.
      MAIN OUTCOME MEASUREMENTS: Standard 4-point bending tests were performed to
      obtain stiffness and failure load values. RESULTS: Liquid cement had a 1.38 times
      increase in stiffness and a failure load 1.84 times greater compared with paste
      cement, regardless of hole size with a gap at the fracture site (P < 0.05).
      Liquid cement had a force to failure of 1.77 and 1.91 times in the standard-sized
      and oversized holes, respectively, when compared with paste cement (P < 0.05).
      CONCLUSIONS: When the cement was inserted in a liquid state in a plated femoral
      diaphyseal fracture with a gap, screw purchase augmentation achieved greater
      bending stiffness and resisted a greater failure load.

PMID- 18827595
TI  - Shortening osteotomy and compression plating for atrophic humeral nonunions:
      surgical technique.
AB  - The incidence of nonunion after humeral shaft fractures is low with both
      operative and nonoperative interventions. However, when a delayed union or
      nonunion occurs, it can be a very debilitating, leading to limited function and
      pain. Several methods have been described for the management of humeral
      diaphyseal nonunions. We present 11 cases managed with a transverse, shortening
      osteotomy and compression plating with or without bone grafting. Of the 11 cases,
      10 had prior surgical treatment of open reduction and internal fixation. Union
      was achieved in all 11 humeri.

PMID- 18827596
TI  - A technique for removal of broken cannulated tricortical syndesmotic screws.
AB  - Breakage rates of tricortical syndesmotic screws after weight bearing range from
      10% to 29%. Removal of the portion of the broken screw buried within the tibia
      often proves quite difficult. We report a new technique to remove a broken
      cannulated syndesmotic screw. This technique is simple, time saving, and less
      traumatic than previously reported methods of broken syndesmotic screw removal.

PMID- 18827597
TI  - Severely comminuted bicondylar tibial plateau fractures in geriatric patients: a
      report of 2 cases treated with open reduction and postoperative external
      fixation.
AB  - We present 2 cases of C3-type fractures of the tibial plateau in geriatric
      patients. Our treatment concept--in particular the use of postoperative external
      fixation--is not yet described in the recent literature and includes initial
      external fixation, internal fixation after soft tissue consolidation using a
      median incision, filling of the metaphyseal comminution zone with allogenic
      cancellous bone obtained from a femoral head, anteromedial and anterolateral
      fixed-angle double plating, and external fixation postoperatively until osseous
      healing. The described treatment plan does not provide a valid alternative for
      the treatment of bicondylar fractures in younger patients. It may be an option
      for the treatment of C3-type fractures in geriatric patients only.

PMID- 18827598
TI  - Rotational acetabular osteotomy for osteonecrosis of the femoral head after
      intracapsular fracture of the neck of the femur.
AB  - The treatment of osteonecrosis of the femoral head in younger patients varies
      among orthopaedic surgeons. In particular, the optimal treatment of extensive
      osteonecrosis associated with femoral head collapse remains controversial. Since
      1995, we have performed rotational acetabular osteotomy on 70 hips, including
      those of 3 patients with extensive osteonecrosis of the femoral head after
      intracapsular fracture of the neck of the femur. In all 3 patients, adequate
      coverage of the femoral head by the osteotomized acetabulum was obtained, and
      their symptoms (especially pain) showed marked improvement at latest follow-up.

PMID- 18827599
TI  - Periprosthetic knee fractures.
AB  - Fractures of the distal femur, proximal tibia, and patella that occur adjacent to
      a total knee replacement may be very difficult to treat. Fixation options are
      compromised because of the short articular segment, frequent comminution, pre
      existing osteoporosis, previous surgical incisions, and the presence of the knee
      implant itself. This review article summarizes current concepts regarding the
      incidence, classification, treatment options, and outcomes for periprosthetic
      fractures of the knee.

PMID- 18827601
TI  - Re: prognostic reliability of the Hawkins sign in fractures of the talus.

PMID- 18827602
TI  - Telomeres and telomerase in lung cancer.
AB  - Protected telomeres ensure normal chromosomal segregation during mitosis but at
      the same time can endow genetically abnormal cancer cells with immortality.
      Telomerase has a pivotal role in telomere protection, both in normal and cancer
      cells. Understanding the functional interplay between telomere shortening and
      telomerase expression in cancer cells is of critical importance to elucidating
      the precise mechanisms by which these cells are able to bypass telomere crisis
      and become immortal.

PMID- 18827603
TI  - Inhibition of Hsp90 leads to cell cycle arrest and apoptosis in human malignant
      pleural mesothelioma.
AB  - INTRODUCTION: Heat shock protein 90 (Hsp90) is an abundant molecular chaperone
      that mediates the maturation and stability of a variety of proteins associated
      with the promotion of cell growth and survival. Inhibition of Hsp90 function
      leads to proteasomal degradation of its mis-folded client proteins. Recently,
      Hsp90 has emerged as being of prime importance to the growth and survival of
      cancer cells and its inhibitors have already been used in phase I and II clinical
      trials. METHODS: We investigated how 17-allylamino-17-demethoxygeldanamycin (17
      AAG), a small molecule inhibitor of Hsp90, is implicated in human malignant
      pleural mesothelioma (MM). RESULTS: We found that 17-AAG led to significant G1 or
      G2/M cell cycle arrest, inhibition of cell proliferation, and decrease of AKT,
      AKT1, and survivin expression in all human malignant pleural mesothelioma cell
      lines examined. We also observed significant apoptosis induction in all MM cell
      lines treated with 17-AAG. Furthermore, 17-AAG induced apoptosis in freshly
      cultured primary MM cells and caused signaling changes identical to those in 17
      AAG treated MM cell lines. CONCLUSION: These results suggest that Hsp90 is
      strongly associated with the growth and survival of MM and that inhibition of
      Hsp90 may have therapeutic potential in the treatment of MM.

PMID- 18827604
TI  - An alternative method for screening EGFR mutation using RFLP in non-small cell
      lung cancer patients.
AB  - INTRODUCTION: Epidermal growth factor receptor (EGFR) mutations are strong
      determinants of tumor response to EGFR tyrosine kinase inhibitors in non-small
      cell lung cancers (NSCLCs). Currently available methods of EGFR mutation
      detection rely on direct sequencing. Here, we describe the use of an alternative
      way to screen EGFR mutations. METHODS: A total of 109 frozen tumor specimens from
      NSCLC patients were obtained. For mutational analysis of EGFR exons 18, 19, and
      21, reverse transcription-polymerase chain reaction was performed on the cDNA
      using original primers designed for restriction fragment length polymorphism
      (RFLP). RESULTS: EGFR mutations were detected in 37 patients (34%) by both RFLP
      and direct sequencing except one case in which it was detected only by RFLP. EGFR
      mutations were more frequently observed to be significant by multivariate
      analysis in patients with adenocarcinoma (OR = 5.56), no-smoking history (OR =
      4.34), and 65-year-old or younger (OR = 2.64), but not in women (OR = 1.14).
      Among 37 patients, 18 were treated with gefitinib and 9 responded to the
      treatment. One patient without any mutation responded. CONCLUSION: RFLP is a
      useful method for screening EGFR mutations and can also be applied to predicting
      the sensitivity of NSCLC patients to EGFR-tyrosine kinase inhibitors.

PMID- 18827605
TI  - Epidermal growth factor receptor intron-1 polymorphism predicts gefitinib outcome
      in advanced non-small cell lung cancer.
AB  - INTRODUCTION: Epidermal growth factor receptor (EGFR) gene intron 1 contains a
      polymorphic single sequence dinucleotide repeat (CA)n whose length has been found
      to inversely correlate with transcriptional activity. This study was designed to
      assess the role of (CA)n polymorphism in predicting the outcome of gefitinib
      treatment in advanced non-small cell lung cancer (NSCLC). METHODS: Blood and
      tumor tissue from 58 patients with advanced NSCLC submitted to gefitinib were
      collected. EGFR intron 1 gene polymorphism, along with EGFR gene mutation, gene
      copy number and immunohistochemistry expression were determined. Moreover, a
      panel of lung cancer cell lines characterized for EGFR intron 1 polymorphism was
      also studied. RESULTS: EGFR intron 1 polymorphism showed a statistically
      significant correlation with the gefitinib response (response rate 25 versus 0%,
      for patients with a (CA)16 and with a (CA)else genotype, respectively; p =
      0.044). Patients with a (CA)16 genotype had a longer survival compared with those
      with a (CA)else genotype (11.4 versus 4.8 months, respectively; p = 0.037). In
      addition, cell lines lacking the (CA)16 allele showed a statistically significant
      higher IC50 compared with cell lines bearing at least one (CA)16 allele (p =
      0.003). CONCLUSIONS: This study supports a potential role of EGFR intron 1
      polymorphism in predicting the outcome of gefitinib treatment in advanced NSCLC.

PMID- 18827606
TI  - Clinical efficacy and predictive molecular markers of neoadjuvant gemcitabine and
      pemetrexed in resectable non-small cell lung cancer.
AB  - BACKGROUND: A trial of neoadjuvant gemcitabine and pemetrexed (GP) chemotherapy
      in patients with resectable non-small cell lung cancer was conducted. The goal
      was to achieve a disease response rate of 50% and to determine if the expression
      levels of genes associated with GP metabolism are predictive of response.
      METHODS: Patients had staging with a computed tomography scan, whole body F-18
      fluorodeoxyglucose positron emission tomography, and mediastinoscopy. Four
      biweekly cycles of GP were given. Patients were restaged, and those with
      resectable stage IB-III disease had thoracotomy. Fresh frozen tumor specimens
      were collected before and after chemotherapy and the mRNA levels of 14 target
      genes determined by real-time reverse transcription polymerase chain reaction.
      RESULTS: Fifty-two patients started therapy. The radiographic disease response
      rate was 35% (95% confidence interval 21.7-49.6%), and the progression rate was
      6%. Forty-six patients had a thoracotomy. The complete tumor resection rate was
      77% (40/52). There were no perioperative deaths or deaths related to
      chemotherapy. Tumor response to chemotherapy was inversely correlated with the
      level of expression of RRM1 (p < 0.001; regulatory subunit of ribonucleotide
      reductase) and TS (p = 0.006; thymidylate synthase); i.e., the reduction in tumor
      size was greater in those with low levels of expression. CONCLUSIONS: Neoadjuvant
      GP is well tolerated and produces an objective response rate of 35%. Tumoral RRM1
      and TS mRNA levels are predictive of disease response and should be considered as
      parameters for treatment selection in future trials with this regimen.

PMID- 18827607
TI  - Circulating serum vascular endothelial growth factor is not a prognostic factor
      of non-small cell lung cancer.
AB  - INTRODUCTION: High circulating serum vascular endothelial growth factor (VEGF)
      levels might reflect enhanced angiogenesis in patients suffering from non-small
      cell lung cancer (NSCLC). This study aimed at determining the prognostic
      significance of circulating VEGF as a prognostic factor in NSCLC. METHODS: Four
      hundred fifty-one histologically or cytologically proven and previously untreated
      NSCLC patients have been studied. Median follow-up was 13 years and 9 months.
      Eleven clinical and biologic variables were recorded. The levels of circulating
      VEGF were measured in the serum by quantitative immunoassay. Patients have had
      received conventional treatment (without anti-VEGF therapy) according to the
      international guidelines. All statistical tests were two-sided. RESULTS: Receiver
      operating characteristic curves (area under the ROC curve: 0.66 +/- 0.05) showed
      that circulating VEGF serum level did not demonstrate a high sensitivity
      specificity relationship, and therefore, demonstrated a low ability to
      differentiate NSCLC from benign lung diseases. A 600 pg/mL level of circulating
      VEGF serum was considered as threshold with 40.8% of NSCLC patients presenting
      with a high level. The circulating VEGF distribution differed significantly
      according to disease stage, nodal status, and performance status (PS), with the
      highest levels observed in metastatic stage, positive mediastinal nodal status,
      and poor PS. In univariate survival analysis, patients with a high pretreatment
      circulating VEGF serum level proved to have a shorter overall survival when
      compared with patients presenting with a circulating VEGF serum level </=600
      pg/mL. However, in the Cox proportional hazard model, this variable was not
      included in the panel of independent determinants of a poor outcome that was as
      follows: advanced or metastatic diseases according to the 6th edition of the
      staging system, PS >/=2, nodal status N2-3, metastatic disease, neuron-specific
      enolase >12.5 ng/mL, CYFRA 21-1 >3.6 ng/mL. CONCLUSION: The prognostic
      information given by a high circulating VEGF serum level is not an independent
      determinant of survival owing to a high relationship with main prognostic
      variables such as PS, stage of the disease, and nodal status. This finding does
      not preclude a putative prognostic impact of in situ detection of VEGF and VEGF
      receptors in tumor specimen.

PMID- 18827608
TI  - Significance of Smoking as a Postoperative Prognostic Factor in Patients with Non
      small Cell Lung Cancer.
AB  - INTRODUCTION: In this study, we investigated the influence of smoking on the
      postoperative prognosis in patients with non-small cell lung cancer. METHODS: The
      subjects consisted of 770 patients who underwent a resection of lung cancer in
      our department between 1994 and 2005. We compared the clinico-pathological
      findings between the smoking and never-smoking groups. The pack-year index (PYI)
      was used as a smoking index. RESULTS: The smoking group consisted of 569 patients
      (74%), and the never-smoking group consisted of 201 patients (26%). The smokers
      were composed of 492 men and 77 women. Among the adenocarcinoma patients, there
      were 293 (61%) smokers and 185 (39%) never-smokers. The patients with squamous
      cell carcinoma included 204 (95%) smokers and 10 (5%) never-smokers. The
      proportion of patients with stage IA disease was significantly higher in the
      never-smokers than that of the smokers. The 5-year survival rate after surgery
      was 66% in the never-smoking group; however, the rates were 56% in patients with
      a PYI more than or equal to 20, and 55% in those with PYI more than 20. Seventy
      nine (13.9%) patients in the smoking group and seven (3.5%) patients in the never
      smoking group died of other diseases, with a significant difference (p < 0.01).
      Of these patients, 44 (56%) and 13 (16%) in the smoking group died of respiratory
      and cardiovascular disorders, respectively. In our series, excluding those who
      died of other diseases, there were no significant differences in the
      postoperative prognosis. CONCLUSIONS: In the smoking group, the prognosis was
      poorer than that in the never-smoking group. The higher proportion of early stage
      disease (stage IA) and female gender were major causes of the better prognosis of
      the never-smokers. Nevertheless, the high pulmonary/cardiovascular complication
      related mortality was another cause of the poor prognosis of the smokers with
      lung cancer.

PMID- 18827609
TI  - Should patient-rated performance status affect treatment decisions in advanced
      lung cancer?
AB  - INTRODUCTION: The Eastern Cooperative Oncology Group (ECOG) score is a well known
      prognostic factor and almost always used to determine eligibility for clinical
      trials. The patient-rated performance status score (Pt-PS), section of the
      patient generated subjective global assessment scale, has identical criteria to
      the physician-rated ECOG scale (MD-PS). We compared the Pt-PS with MD-PS in
      patients with advanced non-small cell lung cancer and compared the effect of each
      rating on eligibility for a hypothetical clinical trial. METHODS: Consecutive
      patients with newly diagnosed advanced non-small cell lung cancer completed a
      patient generated subjective global assessment self-rated questionnaire, which
      was then correlated (kappa statistic) with the ECOG PS recorded at the same time.
      Patients were treated with standard chemotherapy. Survival was determined using
      Kaplan-Meier statistics. RESULTS: One hundred nine patients (M:F-54:55) were
      recruited. Pt-PS differed from MD-PS in 59 (54%) instances (p = 0.0001). When
      scores were not congruent, 41/59 (69%) patients evaluated themselves as having a
      worse PS than the physician's rating. Pt-PS was 0 to 1 in 60 (55%) patients
      whereas MD-PS was 0 to 1 in 78 (72%) patients. The functional status irrespective
      of evaluator was predictive of survival (p = 0.001 for MD-PS and p = 0.001 for Pt
      PS). However, the median survival in those with MD-PS >/=2 was 3.3 (CI; 1.7-4.9)
      months whereas individuals with Pt-PS >/=2 had a median survival of 6.2 (CI; 5.4
      6.9) months. CONCLUSIONS: Pt-PS and MD-PS were not congruent in over half of the
      cases, with Pt-PS scores usually poorer. Almost half the patients would have
      excluded themselves from a hypothetical clinical trial (Pt-PS >/=2). This
      requires prospective evaluation.

PMID- 18827610
TI  - Symptom assessment in relapsed small cell lung cancer: cross-validation of the
      patient symptom assessment in lung cancer instrument.
AB  - INTRODUCTION: Lung cancer symptoms can be burdensome for patients with small cell
      lung cancer (SCLC). Patient Symptom Assessment in Lung Cancer (PSALC), a self
      report scale for assessing SCLC symptom burden, was developed and validated
      previously using intravenous topotecan clinical trial data. This study cross
      validates the PSALC using oral topotecan (OT) trial data. METHODS: Data were
      analyzed from a randomized, open-label, multicenter trial including 71 patients
      with relapsed SCLC receiving OT with best supportive care and 70 patients
      receiving best supportive care alone. PSALC and EQ-5D were administered at
      baseline and at 3-week intervals. Internal consistency, reliability, construct
      validity, and responsiveness were evaluated. RESULTS: Only one factor was
      indicated in factor analysis, hence PSALC total score (PSALC-TS) was used for
      psychometric analysis. Internal consistency was supported by Cronbach's alpha of
      0.78. Construct validity was supported by significant associations of higher
      PSALC-TS (higher symptom burden) with worse Eastern Cooperative Oncology Group
      performance status and by correlations of PSALC-TS with EQ-5D utility index and
      visual analog scale score (all p < 0.001). Reliability was supported by
      intraclass correlation coefficient of 0.68 (using PSALC-TS before clinical status
      change) and concordance correlation coefficient of 0.69 (using PSALC-TS at
      baseline and before first visit). PSALC-TS was responsive to clinical status
      change from baseline to tumor response (responsiveness statistic = -0.99) and to
      tumor progression (responsiveness statistic = 0.94). CONCLUSIONS: Consistent with
      prior psychometric results, this cross-validation study using OT trial data
      showed acceptable validity, reliability, and responsiveness of the PSALC scale,
      further supporting its use to measure symptom burden in previously treated SCLC.

PMID- 18827611
TI  - Impact of information on quality of life and satisfaction of non-small cell lung
      cancer patients: a randomized study of standardized versus individualized
      information before thoracic surgery.
AB  - INTRODUCTION: Most cancer patients want to be informed as much as possible. We
      conducted a randomized trial comparing the impact of additional written
      information to oral information only on quality of life (QoL) and satisfaction of
      non-small cell lung cancer patients. PATIENTS AND METHODS: Non-small cell lung
      cancer patients undergoing thoracic surgery were eligible. Patients were
      randomized to receive oral information only or oral plus written information
      describing the disease and its associated surgery and outcomes. QoL was assessed
      by Psychologic Global Well-Being Index. Patients' satisfaction was assessed by
      questionnaire of satisfaction of hospitalized patients. RESULTS: One-hundred two
      patients were included, full data were available for 75 of them (10 early deaths,
      4 lost to follow-up, and 13 with incomplete questionnaires). QoL scores
      (baseline, 3 months) were comparable between both groups. In contrast, patients
      receiving oral plus written information were significantly dissatisfied with
      regard to several aspects of care regarding staffs as well as the structure. The
      information group significantly influenced satisfaction levels at multivariate
      analysis (standardized beta coefficient, -0.26, p = 0.04). CONCLUSIONS:
      Unexpectedly, at the end of their hospital stay, patients receiving both oral and
      written information experienced a statistically significant lower level of
      satisfaction, whereas no difference in QoL between both groups were highlighted.
      Further research is needed on patient's information.

PMID- 18827612
TI  - A phase II study of oxaliplatin, pemetrexed, and bevacizumab in previously
      treated advanced non-small cell lung cancer.
AB  - INTRODUCTION: Single agent chemotherapy is standard for second and third line
      treatment of non-small cell lung cancer (NSCLC). Combination therapy to date has
      not proven to be superior to single agents in this setting, often adding toxicity
      without any additional efficacy. We investigated the activity and tolerability of
      the combination of oxaliplatin, pemetrexed, and bevacizumab in patients with
      previously treated advanced NSCLC. METHODS: This multicenter phase II trial
      evaluated the safety and efficacy of the combination of pemetrexed (500 mg/m),
      oxaliplatin (120 mg/m), and bevacizumab (15 mg/kg), given every 21 days, in
      patients with previously treated advanced NSCLC. Eligibility criteria included
      performance status 0 to 1, nonsquamous histology, and at least one prior
      chemotherapy regimen. Patients with treated brain metastases were allowed. The
      primary end point was response rate, with secondary endpoints of progression-free
      survival and overall survival. RESULTS: Thirty-six patients were enrolled on this
      study. Treatment was well tolerated; the most common grade 3 toxicity was
      hypertension, which was easily managed with oral medications. The nine (25%)
      patients with treated brain metastases had no episodes of cerebral hemorrhage. Of
      the 34 patients evaluable for tumor response, none had complete response, nine
      (27%) had partial response, 15 (44%) had stable disease, and 10 (29%) had
      progressive disease. Median progression-free survival was 5.8 months (95%
      confidence interval 4.1-7.8 months) and median overall survival was 12.5 months
      (95% confidence interval 7.3-17 months). CONCLUSIONS: Treatment with oxaliplatin
      and pemetrexed in combination with the targeted antiangiogenic agent bevacizumab
      yielded promising efficacy with manageable toxicity in the previously treated
      advanced NSCLC population.

PMID- 18827613
TI  - Phase II randomized study of dose-dense docetaxel and cisplatin every 2 weeks
      with pegfilgrastim and darbepoetin alfa with and without the chemoprotector
      BNP7787 in patients with advanced non-small cell lung cancer (CALGB 30303).
AB  - INTRODUCTION: We investigated dose-dense docetaxel and cisplatin in patients with
      measurable non-small cell lung cancer in a randomized phase II study without [A]
      or with [B] a putative chemoprotective agent, BNP7787. PATIENTS AND METHODS:
      Chemotherapy-naive patients with stage IIIB (effusion) or IV, performance status
      0 to 1, and adequate organ function were eligible. Treatment with docetaxel 75
      mg/m followed by cisplatin 75 mg/m over 1 hour day 1 with darbepoetin 200 mug day
      1 and pegfilgrastim 6 mg day 2 without/with BNP7787 before cisplatin was repeated
      every other week for up to 6 cycles. The primary end point was to differentiate
      between grade >/=2 neurotoxicity rates of 30% on [A] and 10% on [B]. Feasibility
      was prospectively defined as febrile neutropenia in <10% of patients and </=1
      treatment delay per cycles 1 to 3 and 4 to 6 in <20% of patients. RESULTS: Of 160
      patients enrolled, 5 never started therapy and 4 were ineligible. Neurotoxicity
      grade >/=2 occurred in 32% on [A] and 29% on [B]. The incidence of febrile
      neutropenia was 4% on [A] and 3% on [B]. Treatment delays occurred in 13% and 20%
      of patients on [A] and [B], respectively. Completion rates for 3/6 cycles were
      84%/51% on [A] and 84%/53% on [B]. Objective response rates were 55% on [A] and
      51% on [B]. Median progression-free/overall survival times were 5.5/10.7 on [A]
      and 6.5/14.1 month on [B]. CONCLUSIONS: This dose-dense treatment regimen is
      active, feasible, and tolerable. Its further investigation in the curative
      setting in non-small cell lung cancer should be considered. BNP7787 did not
      result in significant protection from neurotoxicity.

PMID- 18827614
TI  - A phase II trial of gefitinib monotherapy in chemotherapy-naive patients of 75
      years or older with advanced non-small cell lung cancer.
AB  - BACKGROUND: Gefitinib has shown modest activity in patients with recurrent non
      small cell lung cancer (NSCLC) after platinum-based chemotherapy. However, the
      activity of gefitinib as first-line chemotherapy remains unclear, especially
      unknown in elderly patients. A multicenter phase II trial was conducted to
      evaluate the efficacy and tolerability of gefitinib for elderly patients with
      chemotherapy-naive NSCLC. METHODS: Elderly chemotherapy-naive patients with
      advanced NSCLC, ECOG PS of 0-2, and adequate organ functions received 250 mg/day
      of gefitinib. The primary objective of this study was to determine the objective
      response rate (RR). Secondary endpoints were tolerability, disease-related
      symptom using lung cancer subscale (LCS) in FACT-L, progression free survival
      (PFS) and overall survival (OS). We investigated mutation status of the epidermal
      growth factor receptor (EGFR) gene in cases with available tumor samples.
      RESULTS: Fifty patients were enrolled, of whom 49 were eligible. Median age
      (range) was 80 (75-90) years. Thirty-two patients were female (65%) and 40
      patients had adenocarcinoma (82%). The objective RR was 25% (CI 95%, 13-39).
      Median survival time was 10 months (CI 95%, 7-20) and 1-year survival rate was
      50%. The most frequent adverse events were skin disorders (76%). Fifteen patients
      (30%) experienced toxicities >/=grade 3. There were four patients with possible
      interstitial lung disease including two treatment-related deaths. Symptom
      improvement rate using LCS was 49% at 4 weeks of gefitinib therapy. Tumor samples
      from 17 patients were analyzed for EGFR mutation status. EGFR mutations were
      detected in tumor tissues from 7 patients, of which 5 had partial responses
      (71%). CONCLUSIONS: Gefitinib monotherapy is effective and relatively well
      tolerated in chemotherapy-naive elderly patients with advanced NSCLC. Gefitinib
      has potential as a first-line therapeutic option in elderly patients with
      advanced NSCLC.

PMID- 18827615
TI  - Recurrent laryngeal nerve palsy on integrated positron emission tomography
      computed tomography.

PMID- 18827616
TI  - Targeting angiogenesis in the treatment of lung cancer.
AB  - Inhibition of angiogenesis now plays a central role in the management of many
      malignancies. Angiogenesis plays an important role in lung cancer and increasing
      numbers of antiangiogenesis agents are being investigated in all types of
      pulmonary malignancies. The monoclonal antibody, bevacizumab, has demonstrated
      efficacy (improved response rates and overall survival) in phase II and III
      trials in combination with standard first-line chemotherapy in non-small cell
      lung cancer. However patients in the large phase III studies were highly selected
      to reduce the risk of fatal hemoptysis. Many small molecule tyrosine kinase
      inhibitors, particularly sorafenib, sunitinib, vandetanib, and cediranib, are
      currently being investigated in phase III trials as monotherapy or in combination
      with standard therapy. Alternative antiangiogenesis approaches such as vascular
      endothelial growth factor-trap and anticoagulation are also being investigated.
      Targeting angiogenesis is an exciting and attractive area in the treatment of
      lung cancer, and the results of ongoing trials are eagerly awaited. More work is
      required to identify subgroups of patients most likely to benefit from these
      drugs.

PMID- 18827617
TI  - Biphasic pulmonary blastoma with germ cell differentiation in a 36-year-old man.
AB  - We describe the clinical and pathologic findings of a young man with a
      heterogeneous mediastinal tumor metastatic to both lungs, and containing a
      predominant pattern of classic biphasic pulmonary blastoma with elements of
      immature teratoma, seminoma, and embryonal carcinoma. Beta-human chorionic
      gonadotropin and alpha-fetoprotein were elevated at presentation and responded to
      four cycles of bleomycin, etoposide, and cisplatin although the tumor did not
      regress. The patient ultimately progressed through paclitaxel, ifosfamide, and
      cisplatin and tandem autologous bone marrow transplants. Classic biphasic
      pulmonary blastoma is a rare tumor of young adults. Surgery is the primary
      treatment, but prognosis is poor and chemotherapy and radiation have been used
      for unresectable disease. A discussion of pulmonary blastoma and extragonadal
      germ cell tumors is presented.

PMID- 18827618
TI  - Pemetrexed-induced typhlitis in non-small cell lung cancer.
AB  - Pemetrexed is U.S. Food and Drug Administration-approved as a second line, single
      agent treatment of recurrent metastatic non-small cell lung cancer.
      Gastrointestinal side effects, including stomatitis, diarrhea, and vomiting are
      reported to be less than 1% and rarely severe. In the premetrexed clinical trial
      database of 1327 patients, various types of colitis were reported by a total of
      nine patients (0.6%). Typhilitis is a gastrointestinal complication of
      chemotherapy, which presents as fever and abdominal pain. The diagnosis is
      supported by the findings of bowel wall thickening on computed tomographic
      imaging. Typhilitis is usually seen in the setting of severe chemotherapy-induced
      neutropenia for acute leukemia. Nevertheless, it is increasingly recognized as a
      complication of therapy in solid tumors. We present the first documented case of
      typhilitis after treatment with pemetrexed and successful therapy with supportive
      treatment.

PMID- 18827619
TI  - EUS-FNA of enlarged necrotic lymph nodes may cause infectious mediastinitis.
AB  - Transesophageal endoscopic ultrasound with fine-needle aspiration (EUS-FNA) is a
      minimally invasive technique to investigate the mediastinum. Although EUS-FNA can
      be considered in general as a safe technique, complications do occur. We here
      report an infectious complication of EUS-FNA that occurred after puncture of a
      large malignant necrotic mediastinal lymph node.

PMID- 18827620
TI  - Proceedings of the IASLC International Workshop on Advances in Pulmonary
      Neuroendocrine Tumors 2007.
AB  - The International Association for the Study of Lung Cancer, (IASLC) International
      Congress on Advances in Pulmonary Neuroendocrine Tumors was a two-day meeting
      held at the Royal Brompton Hospital in London, United Kingdom on the thirteenth
      and forteenth of December 2007. The meeting was led by 14 member international
      faculty-in the disciplines of pathology, surgery, medicine, oncology,
      endocrinology, nuclear medicine, diagnostic imaging, and biostatistics. The aims
      were twofold, as an educational meeting, and to develop the IASLC International
      Pulmonary Neuroendocrine Tumors Registry. The meeting highlighted the difference
      in presentation of the tumors, management options for early and advanced stage
      disease including the use of novel agents and approaches. The need, process, and
      approach to an International Registry of Pulmonary Neuroendocrine Tumors were
      emphasized. International collaboration to develop a retrospective registry,
      prospective data collection, virtual tissue bank, and collaborative clinical
      trials were universally agreed as the best way to advance our understanding and
      treatment of these rare tumors.

PMID- 18827621
TI  - Rapid detection of hotspot mutations in epidermal growth factor receptor by
      polymerase chain reaction facilitates the management of non-small cell lung
      cancer.

PMID- 18827622
TI  - Selection or work-up bias: a recurrent caveat in evaluation of new diagnostic
      modalities.

PMID- 18827624
TI  - In reference to 3 Tesla delayed contrast magnetic resonance imaging evaluation of
      Meniere's disease.

PMID- 18827625
TI  - In reference to cochleovestibular anomalies in children with cholesteatoma.

PMID- 18827627
TI  - Abstracts of Plastic Surgery 2008. November 2-5, 2008.

PMID- 18827629
TI  - Community-acquired methicillin-resistant staphylococcus aureus: diagnosis and
      treatment update for plastic surgeons.
AB  - LEARNING OBJECTIVES: : After studying this article, the participant should be
      able to: 1. Identify risk factors associated with community-acquired methicillin
      resistant Staphylococcus aureus. 2. Recognize the clinical presentation of
      patients with community-acquired methicillin-resistant S. aureus. 3. Understand
      the treatment and indications for decolonization of patients who have community
      acquired methicillin-resistant S. aureus infections. SUMMARY: : Community
      acquired methicillin-resistant Staphylococcus aureus has evolved over the past 10
      years as a new health threat seen by plastic surgeons and is an increasing cause
      of soft-tissue infections. This pathogen has several distinct virulence factors
      and unique antimicrobial susceptibilities that distinguish methicillin-resistant
      S. aureus from traditional hospital-acquired methicillin-resistant S. aureus.
      This article reviews the epidemiology, risk factors, clinical presentation, and
      treatment of community-acquired methicillin-resistant S. aureus.

PMID- 18827630
TI  - The accuracy of computed tomographic angiography for mapping the perforators of
      the deep inferior epigastric artery: a blinded, prospective cohort study.
AB  - BACKGROUND: The deep inferior epigastric artery perforator flap is increasingly
      used for autologous breast reconstruction, with low donor-site morbidity cited as
      a major advantage of this operation. Preoperative imaging of the donor-site
      vasculature is frequently used as a further means of improving operative outcome.
      Computed tomographic angiography has been increasingly described as a preferred
      imaging modality; however, its formal evaluation has not been described in a
      clinical setting. METHODS: A prospective, single-blind, cohort study was
      undertaken on 60 consecutive patients for whom deep inferior epigastric artery
      perforator flap surgery had been planned. Patients who did not undergo the
      procedure during the study period were excluded, with 42 patients ultimately
      included in the study. All computed tomographic angiography scans were obtained
      at a single institution. Perforators were mapped both on angiography and
      intraoperatively using a grid of 4-mm squares centered on the umbilicus. Only
      perforators larger than 1 mm were included in the study. All imaging findings
      were recorded by a single operator, and all intraoperative findings were recorded
      by the operating surgeon. RESULTS: Computed tomographic angiography identified
      280 major perforators in 42 patients. It was highly accurate, demonstrating 279
      perforators recorded accurately, with one false-positive and one false-negative.
      Its sensitivity for mapping perforators was thus 99.6 percent, with a positive
      predictive value of 99.6 percent. CONCLUSIONS: Computed tomographic angiography
      is highly accurate in identifying and mapping the perforators of the deep
      inferior epigastric artery. Its accuracy is superior to that of the previous
      modalities used in this role and suggests the usefulness of this technique before
      deep inferior epigastric artery perforator flap surgery for breast
      reconstruction.

PMID- 18827631
TI  - Prospective, randomized, double-blind trial of local anesthetic infusion and
      intravenous narcotic patient-controlled anesthesia pump for pain management after
      free TRAM flap breast reconstruction.
AB  - BACKGROUND: : This study assessed the efficacy of a continuous infusion pump
      system for postoperative pain control at muscle-sparing transverse rectus
      abdominis musculocutaneous (TRAM) flap donor sites. METHODS: : In this
      prospective, randomized, double-blind trial, a dual-catheter continuous infusion
      pump system was placed in the muscle-sparing TRAM flap donor-site area in all
      patients. Bupivacaine (0.375%; continuous infusion pump group) or isotonic saline
      (control group) was infused at 4 ml/hour. All patients also had a patient
      controlled anesthesia system delivering intravenous narcotics on demand. Pain
      scores, patient satisfaction, narcotic use, milestones of surgical recovery, and
      side effects of narcotics were compared between the two groups. RESULTS: : Forty
      eight patients were included in the study (23 continuous infusion pump patients
      and 25 control patients). The continuous infusion patients used less mean patient
      controlled anesthesia narcotic during the first 2 postoperative days (78.0 mg
      versus 42.7 mg; p = 0.019) and transitioned earlier to oral narcotics than did
      control patients. Patients' overall pain satisfaction scores were significantly
      better in the continuous infusion group than in the control group. There were no
      significant differences between groups with regard to overall abdominal pain
      intensity scores, total narcotic use, length of hospitalization, incidence of
      narcotic side effects, or milestones of surgical recovery. CONCLUSIONS: : The
      continuous infusion pump system appears to be a safe and effective method for
      postoperative donor-site pain management in TRAM flap breast reconstruction
      patients and should be considered for postoperative donor-site pain management.
      However, continuous infusion pump local anesthetic delivery to the muscle-sparing
      TRAM flap donor site did not eliminate narcotic use for pain control.

PMID- 18827632
TI  - Transplantation in identical twins: another option for breast reconstruction.
AB  - BACKGROUND: Deriving their name from the Greek word plastikos, meaning related to
      molding, plastic surgeons have made their reputation by transplanting tissues
      from one area of the body to another to "remold" defects caused by trauma,
      congenital anomaly, or disease. Dr. Joseph Murray, a plastic surgeon, performed
      the first successful kidney transplant between identical twins in 1954. The
      authors present three cases involving the transplantation of perforator flaps
      from one identical twin to another for breast reconstruction, including cases
      using both deep inferior epigastric perforator and superficial inferior
      epigastric artery flaps. METHODS: Three sets of recipient monozygotic twins that
      had breasts treated with mastectomies underwent reconstruction using transplanted
      tissue from their donor monozygotic twins. All sets of twins underwent DNA
      testing to determine that they were monozygotic; therefore, no immunosuppressive
      therapy was indicated. RESULTS: The three sets of recipient monozygotic twins
      underwent successful breast reconstruction using perforator flap transplants from
      their donor monozygotic twins. The operations included two unilateral
      reconstructions (one using a deep inferior epigastric perforator flap and the
      other using a superficial inferior epigastric artery flap) and one bilateral deep
      inferior epigastric perforator reconstruction. Their hospital courses were
      unremarkable. CONCLUSIONS: Transplant surgery continues to evolve in the twenty
      first century. The authors present three cases of breast reconstruction using
      skin flap transplantation as a new option for breast reconstruction.

PMID- 18827633
TI  - Radiation effects and radioprotection in MC3T3-E1 mouse calvarial osteoblastic
      cells.
AB  - BACKGROUND: Little is known about the mechanisms and treatment of radiation
      induced inhibition of craniofacial bone growth. In an earlier study, the
      radioprotector amifostine (WR-2721) administered to rabbits before irradiation
      radioprotected cultured orbitozygomatic complex periosteal osteoblast-like cells.
      This study assessed the effects of amifostine and its active metabolite on the
      radiation survival, function, and phenotype of mouse calvarial osteoblast-like
      cells in a cell culture model. METHODS: MC3T3-E1 newborn mouse calvarial
      osteoblast-like cells underwent gamma-radiation (0 to 10 Gy) in the presence or
      absence of either WR-2721 or WR-1065, its active metabolite (10 to 10 M). The
      effects of radiation with and without drugs were assessed using endpoints of
      colony-forming ability, cell viability, alkaline phosphatase activity, and
      expression of osteoblastic phenotype genes (alkaline phosphatase, collagen type
      I, osteocalcin, and osteopontin). All experiments were replicated at least in
      triplicate. RESULTS: Irradiation resulted in a dose-dependent inhibition of
      clonogenic cell survival. Pretreatment with WR-1065, but not WR-2721, resulted in
      a significant improvement of osteoblast-like cell survival. Specifically, maximum
      radioprotection was observed with 10 M WR-1065 at a clinically relevant 2-Gy dose
      of irradiation. No significant radioprotection was observed at the lower (5 x 10
      M) concentration of WR-1065. Furthermore, radiation seemed to suppress the
      expression of osteoblastic phenotype-related genes in a dose-dependent manner.
      CONCLUSIONS: This study reveals improved survival after irradiation in osteoblast
      like cells treated with WR-1065 in vitro and corroborates previous findings from
      animal models. Further studies using this agent and similar drugs are important
      for devising strategies to prevent radiation-induced inhibition of craniofacial
      bone growth.

PMID- 18827634
TI  - Role of TGF-beta and FGF in the treatment of radiation-impaired wounds using a
      novel drug delivery system.
AB  - BACKGROUND: Despite refinements in radiotherapy, radiation-impaired wound healing
      continues to be a major source of postoperative morbidity with few treatment
      options. The application of polypeptide growth factors has been investigated in
      both the clinical and laboratory settings. The authors used a novel sustained
      release delivery system to examine the effect of transforming growth factor (TGF)
      beta and fibroblast growth factor (FGF) on radiation-impaired wound healing in a
      rodent model. METHODS: Eighty Sprague-Dawley rats underwent dorsal skin surface
      irradiation of 2500 cGy using a medical linear accelerator producing energy of 6
      MeV followed by creation of a full-thickness skin incision. Six groups of 16
      animals underwent either sham irradiation (irradiation control); irradiation
      only; irradiation and unimpregnated delivery system only; or irradiation and
      either TGF-beta, FGF, or TGF-beta plus FGF combined. Four animals from each group
      were euthanized at 4, 7, 14, and 28 days, and the harvested specimens underwent
      ultimate tensile strength testing and histologic evaluation. RESULTS: All five
      irradiated groups had significantly lower ultimate tensile strength than the sham
      irradiated control group at all time points (p < 0.05), thus validating the
      authors' model of radiation-impaired wound healing. Functional analysis
      demonstrated that all three growth factor-treated groups had significantly higher
      tensile strengths than either of the untreated irradiated groups at 14 days after
      wounding (p < 0.05). Histologic evaluation of the irradiated groups revealed
      increased cellularity and more organized collagen architecture of all treated
      groups when compared with the untreated groups, with the most pronounced
      differences seen at 7 days and 14 days after wounding. CONCLUSIONS: This study
      effectively demonstrates that TGF-beta and FGF act individually and
      synergistically when delivered locally by means of a sustained release system to
      improve ultimate tensile strength in an acute postirradiation impaired wound
      healing model.

PMID- 18827635
TI  - Traction-assisted dermatogenesis by serial intermittent skin tape application.
AB  - BACKGROUND: The use of both tissue expanders and skin-stretching devices is
      commonplace in reconstructive surgery. The authors describe a noninvasive
      technique of tissue expansion. METHODS: This article describes a prospective
      study in which 26 consecutive patients consisting of eight male patients and 18
      female patients were recruited for expanding the skin by the authors' devised
      technique of intermittent serial traction Micropore taping of skin at weekly
      intervals. Once the skin was expanded, the scar revision was performed in one or
      two stages by excision and flap advancement. The age range of the patients was 8
      to 48 years. The anatomical regions that underwent scar revision were scalp (n =
      6), face (n = 9), upper limb (n = 6), and lower limb (n = 9). RESULTS: The size
      of the scars to be resurfaced ranged from 35 x 50 mm on the temple to 280 x 130
      mm on the scalp. The average follow-up after surgical correction was 11 months.
      The number of taping sessions ranged from two to 15, with an average of 6.9.
      Fourteen patients had successfully completed the surgical management, and four
      patients are in the midst of treatment. Four patients defaulted on treatment, and
      in four patients, the expansion failed to progress. Illustrative examples of some
      of the cases are described. CONCLUSION: Traction-assisted dermatogenesis is an
      additional method of tissue expansion that is easy and cost effective for
      reconstruction.

PMID- 18827636
TI  - Hydrodissection as key to a natural-appearing otoplasty.

PMID- 18827637
TI  - Refinement in technique for pediatric dermoid cyst excision: technical note.

PMID- 18827638
TI  - Detection of skin perforators by indocyanine green fluorescence nearly infrared
      angiography.

PMID- 18827639
TI  - Scars: a review of emerging and currently available therapies.
AB  - BACKGROUND: With the investigation and potential introduction of several novel
      scar-reducing therapies to the market within the next several years, it is
      germane to review both the pathophysiology of scarring and the safety and
      efficacy of currently available and emerging therapeutic agents. METHODS: An
      extensive review of the English-language literature was conducted using the
      MEDLINE database. RESULTS: A comprehensive review of the pathophysiology of
      scarring and scar management, including both emerging and currently available
      therapies, was completed. Current clinical studies are limited by small sample
      sizes, lack of well-designed controls, and lack of standardized scar outcome
      measurement parameters. CONCLUSIONS: A prominent challenge in the study of scar
      management is the paucity of well-designed, large, randomized, controlled studies
      examining existing scar-reducing techniques. The greatest improvement in scar
      reducing protocols likely entails a polytherapeutic strategy for management.
      Further investigation into the role of inflammation in scarring is paramount to
      the development of improved scar-reducing agents. There is a need for large
      controlled trials using a polytherapeutic strategy that combines existing and
      novel agents to provide a standardized evidence-based evaluation of efficacy.

PMID- 18827640
TI  - Impact of perforator mapping using multidetector-row computed tomographic
      angiography on free thoracodorsal artery perforator flap transfer.
AB  - BACKGROUND: The preoperative localization of thoracodorsal artery perforators has
      been a challenge because of their topographic variation. METHODS: From November
      of 2005 to January of 2007, 25 patients underwent free thoracodorsal artery
      perforator flap transfer for reconstruction of the lower extremities (22 flaps)
      and the head and neck (three flaps). All of the patients underwent multidetector
      row computed tomographic angiography for preoperative perforator mapping. The
      computed tomographic findings were compared with the acoustic Doppler flowmetric
      and intraoperative findings. Surgical outcomes were compared with those of a
      historical group of patients treated before the adoption of computed tomography
      based perforator mapping. RESULTS: The flap sizes ranged from 3 x 5 cm to 27 x 13
      cm. One to four perforators (mean, 2.2) were marked on the three-dimensional
      computed tomographic image for each patient and the locations correlated with the
      handheld Doppler examination. Intraoperatively, all perforators marked were
      confirmed, and three additional perforators that had not been identified on the
      computed tomographic images were observed. All of the flaps survived, with the
      exception of two cases with marginal necrosis. Concrete planning based on
      knowledge of the precise location of the perforators allowed a shorter harvest
      time, minimized the incision for flap harvest, particularly with small flaps, and
      enabled the planned use of multiple perforators for better perfusion or complex
      designs. CONCLUSIONS: Perforator mapping with preoperative multidetector-row
      computed tomographic angiography is valuable for both planning and executing
      thoracodorsal artery perforator flap transfer. The targeted perforator flap
      harvesting allows a safe and straightforward harvest and an elegant
      reconstruction, with less donor-site morbidity.

PMID- 18827641
TI  - Vascularized adipofascial island flap for thenar augmentation in pollicization.
AB  - BACKGROUND: The recommended treatment for Blauth types IIIB and IV congenital
      thumb hypoplasia is index pollicization and amputation of the functionless,
      hypoplastic thumb. Instead of completely discarding the functionless part, the
      authors retain a portion of the soft tissue as an adipofascial vascular island
      flap. This flap is inset at the base of the new thumb to simulate a thenar
      eminence and to improve the appearance of these hands. METHODS: This flap was
      used to augment the thenar base in 14 hands in 14 children. Follow-up ranged from
      1 to 26 years. RESULTS: All pollicizations were successful and there were no
      major complications. All of the adipofascial flaps improved the appearance of the
      thenar eminence and held up their shape in the long term. CONCLUSIONS: Use of an
      adipofascial island flap is recommended for thenar eminence augmentation in index
      pollicization of types IIIB and IV thumb hypoplasia. This tissue improves the
      appearance of the hand, is easy to harvest, and adds no morbidity.

PMID- 18827642
TI  - Splinting after carpal tunnel release: current practice, scientific evidence, and
      trends.
AB  - BACKGROUND: Postoperative splinting is common after carpal tunnel release,
      despite a lack of scientific evidence supporting its value. The purpose of this
      study was to characterize postoperative splinting regimens among hand surgeons
      and to identify trends in splint use after this procedure. METHODS:
      Questionnaires were mailed to members of the American Society for Surgery of the
      Hand. Recipients were asked to record whether and for how long they use splints
      after carpal tunnel release. They were also asked to indicate their training
      (i.e., orthopedic, plastic, or general surgery). Results were compared with those
      of previously conducted surveys. RESULTS: One thousand ninety-one questionnaires
      were returned, for a response rate of 48 percent. Fifty-three percent of
      respondents use splinting postoperatively. Duration of splinting varied
      tremendously, from 1 to 42 days. Splinting patterns were similar across all
      training backgrounds. In comparison with related surveys conducted in 1987 and
      1997, a trend is evident toward less use of splinting after carpal tunnel
      release. CONCLUSIONS: The use and duration of splinting after carpal tunnel
      release vary widely among hand surgeons. This divergence of practice implies that
      there is little therapeutic benefit to splinting after this procedure, a concept
      supported by substantial scientific evidence and by a trend away from splinting
      over the past 20 years.

PMID- 18827643
TI  - Outcomes of secondary reconstruction of ulnar nerve lesions: our experience.
AB  - BACKGROUND: The authors' experience in the management of late ulnar nerve
      injuries is presented. METHODS: A retrospective study of 44 patients with severe
      ulnar nerve injuries was conducted and the outcomes were analyzed in relation to
      various factors, such as age at injury, denervation time, level of injury, length
      of nerve graft, and type of reconstruction (e.g., neurolysis, secondary end-to
      end repair, or nerve grafting). Most patients were late cases who were referred
      to the authors' center for treatment. The mean time between injury and surgery
      was 14.6 months (range, 2 to 64 months). The mean follow-up period was 2.6 years.
      RESULTS: Overall, good and excellent motor results (>or=M3+) were seen in 31 of
      44 cases (70 percent) and good and excellent sensory results were seen in 28 of
      44 cases (64 percent). The age of the patient, level of injury, denervation time,
      length of nerve graft, and type of surgical reconstruction significantly
      influenced the functional outcome. CONCLUSIONS: Functional results were
      significantly better if surgery was performed within 5 months, the length of the
      graft was 5 cm or less, and the patient was younger than 25 years. Advanced
      microsurgical techniques, such as interfascicular neurolysis and the use of
      vascularized nerve grafts or vascularized fascia, should be kept in mind in
      complex and/or previously failed cases.

PMID- 18827644
TI  - Shoulder function after harvesting a thoracodorsal artery perforator flap.
AB  - BACKGROUND: Converting the latissimus dorsi musculocutaneous flap to a
      thoracodorsal artery perforator flap has been reported for breast reconstruction.
      The goal of this article is to evaluate the donor site after harvesting a
      thoracodorsal artery perforator flap in patients who underwent breast surgery and
      to show the advantages of sparing the latissimus dorsi muscle on the function of
      the shoulder. METHODS: Between 2002 and 2004, 22 patients who had a partial
      breast reconstruction using a pedicled thoracodorsal artery perforator flap were
      enrolled in a functional study to evaluate shoulder function postoperatively.
      Latissimus dorsi muscle strength, shoulder mobility, and latissimus dorsi
      thickness were measured by using the MicroFet2, a goniometer, and ultrasound
      examination, respectively. The measurements of the operated and contralateral
      (unoperated) sides were analyzed statistically. RESULTS: When comparing the
      operated sides to the unoperated sides, latissimus dorsi strength seemed to be
      maintained after surgery. Shoulder mobility was also similar in all movements,
      but both active and passive forward elevation and passive abduction were reduced
      significantly after surgery, and latissimus dorsi thickness was not affected by
      harvesting the thoracodorsal artery perforator flaps. No seroma formation was
      found in any of the donor sites. CONCLUSIONS: Donor-site morbidity after
      harvesting a thoracodorsal artery perforator flap was reduced to a minimum.
      Therefore, perforator flaps should be considered in reconstruction whenever
      adequate perforators can be identified and safely dissected.

PMID- 18827646
TI  - The importance of radical intravelar veloplasty during two-flap palatoplasty.
AB  - BACKGROUND: The purpose of this study was to compare the two-flap palatoplasty
      technique for cleft palate repair, with and without radical intravelar
      veloplasty, with special emphasis on the fistula rate and speech outcome.
      METHODS: A retrospective, time-series cohort of 213 consecutive patients with
      primary two-flap palatoplasty before and after the introduction of a radical
      intravelar veloplasty was studied. The main outcome measures were immediate
      postoperative complications, oronasal fistula rate, and speech. A perceptual
      speech evaluation was performed by two speech pathologists and included
      hypernasality, nasal emission, articulation, intelligibility, and overall
      velopharyngeal competence. The need for secondary palate surgery for
      velopharyngeal insufficiency was also analyzed. RESULTS: There were no
      differences in postoperative complications between the two study groups.
      Postoperative morbidity occurred in six patients (2.8 percent) and consisted of
      two patients with respiratory compromise, two patients who required reoperation
      for bleeding, and two patients with oronasal fistula. Perceptual speech
      evaluation demonstrated significantly better speech outcomes (81.9 percent versus
      49.5 percent, p < 0.001) and a significantly lower rate of secondary palate
      surgery for velopharyngeal insufficiency (29 percent versus 6.7 percent, p =
      0.008) in the radical intravelar veloplasty group. The most important predictive
      factor of speech outcome was the addition of a radical intravelar veloplasty
      (odds ratio, 0.175; 95 percent confidence interval, 0.039 to 0.785). CONCLUSIONS:
      Despite study design limitations, such as experience bias and follow-up
      differences, this study demonstrates that radical intravelar veloplasty may
      enhance the functional results of the two-flap palatoplasty without increasing
      postoperative morbidity. A novel classification of the muscle repair is proposed
      based on the amount of muscle dissection and retropositioning.

PMID- 18827647
TI  - Nasoalveolar molding improves appearance of children with bilateral cleft lip
      cleft palate.
AB  - BACKGROUND: Bilateral cleft lip-cleft palate is associated with nasal deformities
      typified by a short columella. The authors compared nasal outcomes of cleft
      patients treated with banked fork flaps to those of patients who underwent
      nasoalveolar molding and primary retrograde nasal reconstruction. METHODS: A
      retrospective review of 26 consecutive patients with bilateral cleft lip-cleft
      palate was performed. Group 1 patients (n = 13) had a cleft lip repair and nasal
      correction with banked fork flaps. Group 2 patients (n = 13) had nonsurgical
      columellar elongation with nasoalveolar molding followed by cleft lip closure and
      primary retrograde nasal correction. Group 3 patients (n = 13) were age-matched
      controls. Columellar length was measured at presentation and at 3 years of age.
      The number of nasal operations was recorded to 9 years. The Kruskal-Wallis and
      Tukey-Kramer tests were used for statistical analysis. RESULTS: Initial
      columellar length was 0.49 +/- 0.37 mm in group 1 and 0.42 +/- 0.62 mm in group
      2. Post-nasoalveolar molding columellar length was 4.5 +/- 0.76 mm in group 2. By
      3 years of age, columellar length was 3.03 +/- 1.47 mm in group 1, 5.98 +/- 1.09
      mm in group 2, and 6.35 +/- 0.99 mm in group 3. Group 2 columellar length was
      significantly greater (p < 0.001) than that of group 1 and not statistically
      different from that of group 3 (p > 0.05). All group 1 patients (13 of 13) needed
      secondary nasal surgery. No nasoalveolar molding patients (zero of 13, group 2)
      required secondary nasal surgery. CONCLUSION: Nonsurgical columellar elongation
      with nasoalveolar molding followed by primary retrograde nasal reconstruction
      restored columellar length to normal by 3 years and significantly reduced the
      need for secondary nasal surgery.

PMID- 18827648
TI  - "Stuffy nose" rhinoplasty: diced cartilage grafts for correction of cleft nasal
      tip deformities.
AB  - BACKGROUND: Numerous techniques exist to address poor nasal tip projection in the
      cleft nose deformity. The authors describe a secondary closed rhinoplasty
      technique using diced cartilage nasal tip grafting. METHODS: Cleft patients who
      previously underwent lower lateral cartilage repositioning with residual poor
      nasal tip projection underwent the "stuffy nose" rhinoplasty technique in which
      diced septal cartilage grafts were placed in a pocket made from a unilateral
      marginal incision over the lower lateral cartilages. Preoperative and follow-up
      (1 year) comparative measurements included (1) columellar length, (2) alar base
      nasal tip-columellar base angle, and (3) lateral tip projection. RESULTS: Twenty
      cleft patients had improvement in nasal form and tip projection from the stuffy
      nose rhinoplasty. Mean change from preoperatively to follow-up was as follows:
      columellar length, 11.3 mm to 13.3 mm (17.7 percent); alar base-nasal tip
      columellar base angle, 42.0 to 33.5 degrees (8.5 degrees, or 20.2 percent
      decrease); and lateral tip projection, 7.7 mm preoperatively to 9.0 mm
      postoperatively (16.9 percent increase). Two patients developed complications
      (one graft exposure and one infection) but healed with conservative treatment.
      Two different patients underwent revisionary nasal surgery but for other concerns
      (alar base asymmetry and internal nasal valve collapse). CONCLUSIONS: The stuffy
      nose rhinoplasty was shown to objectively improve nasal tip projection in cleft
      patients with secondary nasal deformities, with minimal complications and
      decreased need for revisions.

PMID- 18827649
TI  - The importance of vector selection in preoperative planning of bilateral
      mandibular distraction.
AB  - BACKGROUND: The application of distraction osteogenesis is an effective treatment
      for mandibular deficiencies. A priori, a horizontal vector of distraction was
      hypothesized to produce horizontal movement of the mandible and a vertical vector
      of distraction to produce primarily downward vertical elongation of the ramus.
      This study was designed to test this hypothesis. METHODS: A retrospective
      clinical and radiographic review was conducted of all patients who underwent
      bilateral, uniplanar distraction with an external device at the New York
      University Medical Center between October of 1990 and February of 2004 (n = 185).
      A subset of 15 patients was identified who satisfied inclusion criteria and had
      adequate predistraction and postdistraction lateral cephalograms. Cephalometric
      tracings were made and multiple landmarks were assessed before and after
      distraction. RESULTS: A strong correlation was noted between the vector of
      distraction and rotation of the symphyseal plane, movement of the mandibular
      symphysis, and change in interocclusal angle. A horizontal vector of distraction
      resulted in minimal counterclockwise rotation of the symphyseal plane, greater
      downward vertical translation of the mandibular symphysis, and minimal closure of
      an anterior open bite. In contrast, a vertical vector resulted in greater
      counterclockwise rotation of the symphyseal plane, greater horizontal projection
      of the mandibular symphysis, and greater closure of an anterior open bite.
      Mathematical formulas were derived to correlate the distraction vector and
      mandibular movements. CONCLUSIONS: Successful distraction is dependent on
      accurate prediction of outcomes. This study demonstrates that the vector of
      distraction predictably affects the mandibular response during bilateral
      distraction osteogenesis but contradicts the a priori hypothesis.

PMID- 18827650
TI  - Morphologic study of mandibular outer cortex osteotomy.
AB  - BACKGROUND: The purpose of this study was to illustrate the morphologic changes
      of the mandible after outer cortex osteotomy. METHODS: Ten patients had undergone
      mandibular outer cortex osteotomy. By using the true-up and dissection techniques
      based on three-dimensional spiral computed tomography, variables of effect and
      bone regeneration were evaluated 6 months postoperatively. RESULTS: Concavity
      could be seen in the area from which the mandibular outer cortex had been removed
      6 months postoperatively, especially at the external oblique line region. The
      average cup depth was 3.64 +/- 1.67 mm postoperatively. Diminution of bone volume
      was 1.7 +/- 0.5 percent for the entire mandible and 55 +/- 9 percent for the
      local area 6 months postoperatively. Bone regeneration could be seen in the area
      from which the mandibular outer cortex had been removed. Compared with
      immediately postoperatively, the ratio of neoformative bone was 84.6 +/- 7.3
      percent 6 months postoperatively. The main region of bone regeneration was the
      mandibular angle. CONCLUSIONS: Mandibular outer cortex osteotomy is an effective
      technique for reducing the width of the lower face. Masseter muscular movement
      should be restricted postoperatively to prevent hyperostosis at the angle area.

PMID- 18827651
TI  - Raised intracranial pressure in Apert syndrome.
AB  - BACKGROUND: Raised intracranial pressure is a well-known complication of Apert
      syndrome. The current policy in the authors' unit is to monitor these patients
      and only perform surgery when raised intracranial pressure has been diagnosed.
      The authors present their experience with this protocol, as it allows a more
      accurate picture of the natural history of raised intracranial pressure in Apert
      syndrome. METHODS: The records of 24 patients, aged between 7 and 14 years, with
      Apert syndrome who had been managed expectantly (i.e., with no routine
      "automatic" early surgery) were reviewed. Data were collected on the incidence,
      timing, and management of raised intracranial pressure. RESULTS: Twenty of 24
      patients (83 percent) developed raised intracranial pressure. The average age of
      the first episode was 18 months (range, 1 month to 4 years 5 months). Raised
      intracranial pressure was managed with surgery in 18 patients, including two
      patients who underwent shunt procedures for hydrocephalus. Two patients had their
      raised intracranial pressure treated successfully by correcting coexisting upper
      airway obstruction alone. Seven of the 20 patients (35 percent) developed a
      second episode of raised intracranial pressure, on average 3 years 4 months later
      (range, 1 year 11 months to 5 years 9 months). CONCLUSIONS: In Apert syndrome,
      there is a high incidence of raised intracranial pressure, which can first occur
      at any age up to 5 years and may recur despite initial successful treatment.
      Causes of raised intracranial pressure include craniocerebral disproportion,
      venous hypertension, upper airway obstruction, and hydrocephalus. Careful
      clinical, ophthalmologic, respiratory, and radiologic monitoring will allow
      raised intracranial pressure to be diagnosed accurately when it occurs and then
      treated most appropriately.

PMID- 18827653
TI  - Cranial vault expansion in the management of postshunt craniosynostosis and slit
      ventricle syndrome.
AB  - BACKGROUND: Slit ventricle syndrome and postshunt craniosynostosis are uncommon
      complications after shunting procedures for congenital hydrocephalus. Slit
      ventricle syndrome occurs as a complication in 1 to 5 percent of patients after
      shunting procedures for hydrocephalus during infancy. These patients usually have
      had a shunt in place for years, with overdrainage of cerebrospinal fluid
      resulting in very small ventricles. Excessive intracranial decompression may
      result in ventricular collapse with the formation of slit-like ventricles and
      cranial vault collapse with secondary craniosynostosis. METHODS: A retrospective
      review of 12 patients who had undergone cranial vault expansion for management of
      postshunt craniosynostosis and slit ventricle syndrome refractory to other
      treatment modalities was performed. All patients had initially been shunted for
      congenital hydrocephalus and subsequently underwent a mean of 4.9 shunt revisions
      before cranial vault expansion. RESULTS: All 12 patients demonstrated decreased
      ventricular volume, with noncompliant slit-like ventricles in nine of these
      patients. Five patients demonstrated pancraniosynostosis, three patients
      demonstrated multiple sutural fusion, and isolated sagittal synostosis occurred
      in two patients. Two patients appeared to have "functional" synostoses with
      narrowed, overlapping sutures that were not actually fused. Eleven patients
      underwent bilateral fronto-orbital advancement with frontotemporoparietal
      expansion; one patient underwent only posterior vault expansion. Seven of the 12
      patients required a mean of 2.3 shunt revisions after cranial vault expansion;
      five patients did not require subsequent revisions. Improvement in cranial vault
      shape was achieved in all 12 patients, as was improvement of neurologic symptoms
      in nine of the 12 patients. CONCLUSIONS: Cranial vault expansion is a useful
      approach in the management of the restricted cranium associated with slit
      ventricle syndrome and postshunt craniosynostosis. This approach resulted in a
      decreased need for shunt revisions and improvement of neurologic symptoms and
      cranial vault shape.

PMID- 18827654
TI  - Bilateral cleft lip and nasal repair.
AB  - SUMMARY: The bilateral cleft lip and nasal repair has remained a challenging
      endeavor. Techniques have evolved to address concerns over unsatisfactory
      features and stigmata of the surgery. The authors present an approach to this
      complex clinical problem that modifies traditional repairs described by Millard
      and Manchester. The senior author (H.S.B.) has developed this technique with over
      25 years of surgical experience dealing with the bilateral cleft lip. This staged
      lip and nasal repair provides excellent nasal projection, lip function, and
      aesthetic outcomes. Lip repair is performed at 3 months of age. Columellar
      lengthening is performed at approximately 18 months of age. A key component of
      this repair focuses on reconstruction of the central tubercle. A triangular
      prolabial dry vermilion flap is augmented by lateral lip vermilion flaps that
      include the profundus muscle of the orbicularis oris. This minimizes lateral lip
      segment sacrifice and provides improved central vermilion fullness, which is
      often deficient in traditional repairs. The authors present the surgical
      technique and examples of their clinical results.

PMID- 18827655
TI  - Evaluation of age-related intraorbital fat herniation through computed
      tomography.
AB  - BACKGROUND: Progressive herniation of lower eyelid fat has generally been
      accepted as a part of the aging process in the lower eyelid. Numerous theories
      have been proposed for the mechanism of periorbital aging, but to the best of the
      authors' knowledge, the actual occurrence of lower eyelid fat herniation has not
      been documented. METHODS: Using data of orbital and facial computed tomography
      from 167 patients, the authors evaluated curvature and protrusion of lower eyelid
      fat and its changes in different age groups. The relation of its occurrence to
      the position of the ocular globe was also evaluated. RESULTS: A statistically
      significant effect of age groups was detected for curvature (percent) of lower
      eye lid fat. Specifically, when compared with the reference group (younger than
      30 years), each increase of 1 year shows a curvature increase of 0.48 percent for
      the group that was 30 to 69 years old (95 percent confidence interval, 0.27 to
      0.69; p < 0.01). For the age group of 70 years or older, each increase of 1 year
      could predict a 1.22 percent increase of curvature (95 percent confidence
      interval, 0.81 to 1.63; p < 0.01). CONCLUSIONS: The authors found that although
      the amount of lower eyelid fat varies greatly between individuals, the process of
      lower eyelid fat herniation does occur. It retains a steady incline after the
      third decade of life and slows at approximately age 70. In the authors' study,
      ocular globe position appears unrelated to this process of herniation.

PMID- 18827656
TI  - Infrabrow excision blepharoplasty: applications and outcomes in upper
      blepharoplasty in Asian women.
AB  - BACKGROUND: To avoid the somewhat operated look while effectively resolving
      shortcomings inherent in the conventional blepharoplasty technique, the authors
      propose an infrabrow excision blepharoplasty as a satisfying and useful
      alternative. The authors' experience during a 3-year period is presented and
      reviewed. METHODS: Sixty-four patients were operated on by infrabrow excision
      blepharoplasty. The indications for the procedure included those patients with
      one or more of the following criteria: (1) prior infrabrow excision, (2) desire
      to preserve inborn lid crease lines, (3) multiple prior lid operations related to
      double-eyelid operation, (4) lateral lid hooding being the primary concern for
      wanting blepharoplasty, (5) planned or preexisting cosmetic tattoo of the
      eyebrows, and (6) age group in the late 30s through mid-50s, thus excluding the
      most severe forms of blepharochalasia. The mean postoperative follow-up period
      was 13 months, and the photographic results were collected retrospectively and
      evaluated. RESULTS: There was no complication related to surgery in terms of the
      resulting scar and periorbital sensory change. The mean operative time was 35
      minutes. Significant flattening of the eyebrow or lid crease discrepancy
      necessitating additional surgery was not observed. Patient satisfaction was very
      high in terms of both the aesthetic outcome and patient comfort. CONCLUSION:
      Infrabrow excision blepharoplasty can be an easy and satisfying alternative that
      achieves the same goals as a conventional blepharoplasty in a selected group of
      patients.

PMID- 18827657
TI  - Use of porcine acellular dermal matrix (Enduragen) grafts in eyelids: a review of
      69 patients and 129 eyelids.
AB  - BACKGROUND: Spacer grafts in the eyelid are used in both reconstructive and
      aesthetic procedures. The authors report their experience using a new acellular
      porcine dermal graft (Enduragen) in 129 eyelids. METHODS: A retrospective chart
      review was performed that included every case in which Enduragen was used by the
      two primary authors in the upper or lower eyelid. Patient demographics, type of
      procedure performed, and complications were reviewed. RESULTS: Sixty-nine
      patients and a total of 129 eyelids were included in the study. Eight procedures
      were spacers in the upper lid, 104 were for spacers in the lower lid, and 17 were
      for lateral canthal reinforcement. Twenty-two procedures were in primary cases
      and 47 were in eyelids for secondary reconstructions, for a total of 69 patients.
      There were 13 eyelid complications, for a complication rate of 10 percent. Nine
      cases required surgical revision, and there were four cases of infection, all of
      which were successfully treated with oral and topical antibiotics. CONCLUSIONS:
      Enduragen has proved to be a very satisfactory substitute for ear cartilage and
      fascia in eyelid surgery in both reconstructive and primary eyelid cases. It
      seems to be far superior to other commercially available tissue substitutes
      because of its predictability of structure and robust behavior. All problems that
      were encountered in this series seemed to be related more to technical errors
      than to any deficiency in or reaction to the Enduragen. The increased strength,
      rigidity, and durability give support to the lids comparable to that obtained
      with autogenous ear cartilage and fascia.

PMID- 18827658
TI  - Maximizing the aesthetic result in panniculectomy after massive weight loss.
AB  - BACKGROUND: Plastic surgical consultation for abdominal contouring following
      massive weight loss is becoming increasingly prevalent, especially with the
      popularity of surgical weight loss procedures. The authors reviewed their
      experience with a novel panniculectomy technique that generally combines
      horizontal and vertical tissue excision to generate the best contour possible
      while providing effective relief of symptoms related to a dependent abdominal
      panniculus. METHODS: A retrospective chart review was conducted of 100
      consecutive patients who underwent panniculectomy using the authors' technique
      over a 5-year period. Demographic and procedural data were collected, and outcome
      measures were analyzed. RESULTS: Eighty-seven women and 13 men with an average
      weight loss of 133 lb underwent abdominal panniculectomy. A total of 37 ventral
      hernias were repaired concomitantly. Mean clinical follow-up was 16 months.
      Hospital length of stay averaged 4 days, and the most common complications were
      blood transfusion requirement (n = 39), fluid collections (n = 32), tissue
      necrosis requiring debridement (n = 18), and contour irregularities requiring
      revision (n = 15). Overall, 56 patients had a completely uncomplicated recovery.
      Greater amounts of tissue resection were associated with higher rates of
      transfusion (p < 0.01). CONCLUSIONS: The panniculectomy technique described can
      be performed safely and reproducibly. It yields an excellent abdominal contour
      and is effective in alleviating many symptoms of the dependent abdominal
      panniculus. It also provides exposure for improved evaluation and repair of
      concomitant ventral hernia defects.

PMID- 18827659
TI  - Bra-line back lift.

PMID- 18827660
TI  - Tip shaping in primary rhinoplasty: an algorithmic approach.
AB  - BACKGROUND: Underprojection and lack of tip definition often coexist. Techniques
      that improve both nasal tip refinement and projection are closely interrelated,
      and an algorithmic approach can be developed to improve the predictability of the
      dynamic changes that occur. Use of nondestructive and nonpalpable techniques that
      enhance nasal tip shape are emphasized. METHODS: A retrospective review of
      primary rhinoplasty patients was undertaken to delineate the precise role of
      preoperative analysis, intraoperative evaluation, and execution of specific
      surgical techniques in creating nasal tip refinement and projection. Specific
      case studies are used to demonstrate the efficacy and predictability of these
      maneuvers. RESULTS: Successful tip refinement and projection depends on (1)
      proper preoperative analysis of the deformity; (2) a fundamental understanding of
      the intricate and dynamic relationships between tip-supporting structures that
      contribute to nasal tip shape and projection; and (3) execution of the operative
      plan using controlled, nondestructive, and predictable surgical techniques.
      CONCLUSIONS: A simplified algorithmic approach to creating aesthetic nasal tip
      shape and projection in primary rhinoplasty has been established to aid the
      rhinoplasty surgeon in reducing the inherent unpredictability of combined
      techniques and improving long-term aesthetic outcomes.

PMID- 18827661
TI  - Ethical issues for the plastic surgeon in a tumultuous health care system:
      dissecting the anatomy of a decision.
AB  - BACKGROUND: Society anticipates that plastic surgeons will make ethical decisions
      that are solely in the best interest of their patients. However, a variety of
      competing factors exert an influence on all decision-making processes. METHODS:
      Multiple competing factors that commonly influence decision-making by plastic
      surgeons, on both conscious and subconscious levels, are identified. By exploring
      the ramifications of these factors, a more ethical outcome can be achieved.
      RESULTS: Some of these competing interests that can sidetrack ethical decision
      making include personal finances (e.g., ownership of surgical centers, selection
      of procedures, pricing); outside regulations (e.g., Emergency Medical Treatment
      and Active Labor Act of 1986 and care of the uninsured); and professional duty
      (e.g., informed consent, discussion of error). CONCLUSIONS: Plastic surgeons who
      are aware of the competing interests that influence their decision-making
      processes stand a greater chance of achieving ethical outcomes. Nevertheless,
      with the growing volume of nonreimbursed care and expectations of perfect
      outcomes, achieving uniformly ethical decisions without burdensome self-sacrifice
      is difficult at best.

PMID- 18827662
TI  - Randomized controlled trials in plastic surgery: a 20-year review of reporting
      standards, methodologic quality, and impact.
AB  - BACKGROUND: Randomized controlled trials in plastic surgery have not been
      analyzed comprehensively. We analyzed plastic surgical randomized controlled
      trials with respect to reporting standards, methodologic quality, and impact on
      the specialty. METHODS: Randomized controlled trials published from 1986 to 2006
      in three major plastic surgery journals were scored for quality and impact using
      the Consolidated Standards of Reporting Trials checklist, the Jadad criteria,
      citation numbers, and other parameters. The associations between the quality
      scores and multiple independent parameters, including trial impact, were
      explored. The relative impact of randomized controlled trials in plastic surgery
      was compared with that in other specialties. RESULTS: A total of 163 randomized
      controlled trials were evaluated. The average Consolidated Standards of Reporting
      Trials and Jadad scores were 49 percent and 2.3, respectively. There were
      deficiencies in the reporting of parameters that influence bias and statistical
      significance. Randomized controlled trials with high impact or high methodologic
      quality had higher reporting scores. However, the quality and impact scores did
      not correlate with the number of participants, subject category, country of
      origin, or year or journal of publication. Nonsurgical trials had significantly
      higher quality and impact than surgical trials. Randomized controlled trials in
      plastic surgery had relatively lower impact as compared with randomized
      controlled trials in other specialties. CONCLUSIONS: The reporting and
      methodologic standards of randomized controlled trials in plastic surgery need
      improvement. Standards could be improved if well-accepted reporting and
      methodologic criteria are considered when designing and evaluating randomized
      controlled trials. Instituting higher standards may improve the impact of
      randomized controlled trials and make them more influential in plastic surgery.

PMID- 18827663
TI  - Predictive factors in identifying subspecialty fellowship applicants who will
      have academic practices.
AB  - BACKGROUND: The challenge of subspecialty fellowship directors is to recruit
      surgeons who are motivated to continue the tradition of teaching by entering
      academic medicine. The authors looked for predictive factors to help with more
      accurate selection of applicants. METHODS: Application and follow-up data from
      plastic surgery subspecialty fellows in craniofacial surgery, hand surgery, and
      microsurgery from the University of California, Los Angeles were reviewed for the
      years 1987 through 2002 (n = 62). Fellows were divided into three groups as
      follows: group 1, full-time academic; group 2, part-time clinical faculty; and
      group 3, private practice at 1 year and 5 years after fellowship. Common factors
      of fellows within the three groups were listed. RESULTS: Although a majority of
      applicants (95 percent) indicated an aspiration to practice academic medicine,
      only one-third remained in full-time academics 5 years after their subspecialty
      training. There was a trend toward leaving academic practice: the rates at 1 year
      were 74 percent for group 1 (academic) and 5 percent for group 3 (private
      practice), but by 5 years this had equalized (group 1, 34 percent; group 3, 32
      percent). Group 1 (academic) showed more academic productivity publications per
      year, academic titles, editorial boards, and active participation in medical
      societies compared with group 3 (private practice). The factors that were more
      common to group 1 were married or married with children, five or more
      publications, one or more years of research, and 7 or more years of training.
      CONCLUSION: Plastic surgery fellowship directors may look at the following
      predictive factors of applicants if they would like their graduates to carry on
      the tradition of teaching future plastic surgeons: (1) previous dedicated
      research training, (2) more years of clinical training, and (3) more scientific
      publications.

PMID- 18827665
TI  - Taking CME to a new level in plastic and reconstructive surgery.

PMID- 18827666
TI  - Redefining reoperations.

PMID- 18827667
TI  - Surveys: what are they and why should I respond?

PMID- 18827672
TI  - Treatment of simple zygoma fractures.

PMID- 18827673
TI  - Use of tragus cartilage for grafting.

PMID- 18827674
TI  - Breast augmentation today: saline versus silicone--what are the facts?

PMID- 18827675
TI  - A prospective, randomized, double-blind, controlled trial of continuous local
      anesthetic infusion in cosmetic breast augmentation.

PMID- 18827677
TI  - Resection of panniculus morbidus: a salvage procedure with a steep learning
      curve.

PMID- 18827679
TI  - Anatomical landmarks to the superficial and deep palmar arches.

PMID- 18827680
TI  - Beneficial influence of titanium mesh cage on infection healing and spinal
      reconstruction in hematogenous septic spondylitis: a retrospective analysis of
      surgical outcome of twenty-five consecutive cases and review of literature.
AB  - STUDY DESIGN: Single institution, single surgeon retrospective review. OBJECTIVE:
      To investigate if the use of titanium mesh cage on the site of infection could be
      beneficial for successful outcome of the operative treatment for pyogenic
      spondylitis. SUMMARY OF BACKGROUND DATA: There is a controversy concerning the
      optimal treatment for pyogenic spondylitis regarding approach, instrumentation
      and staging. This large series reports on single-stage instrumented open and
      minimally invasive surgery for septic spondylitis. METHODS: Twenty-four patients
      aged 57 +/- 16 years suffering from persistent or complicated septic spondylitis
      were treated by a total of 25 single stage combined surgeries (first: anterior
      debridement/partial vertebrectomy plus mesh cage filled with autologous bone
      graft; second: pedicle screw fixation with open and minimal invasive techniques).
      The indications for surgery included neurologic compromise, significant vertebral
      body destruction with kyphosis associated with segmental instability, failure of
      medical treatment, and/or epidural/ paravertebral abscess formation. Needle
      biopsy was performed in all patients before surgery. Patients were evaluated
      before and after surgery in terms of pain and neurologic level, sagittal
      segmental spinal balance, radiologic fusion and recovery. RESULTS: All but 1
      tetraplegic patient with simultaneous cervical and lumbar spondylitis, who died
      because of massive clot lung embolism 2 months after surgery, were followed for
      56 months (range, 31-116 months) The visual analogue scale score improved from
      6.5 before surgery to 1.8 after surgery. The segmental kyphotic deformity was
      corrected at an average of 6 degrees, without cage settling. An insignificant
      loss of kyphosis correction of an average 0.6 degrees was measured in the
      thoracolumbar junction only. Blood loss, surgical time, and surgical
      complications were significant less in the patients who operated with minimal
      invasive technique. Patients with incomplete neurologic impairment improved after
      surgery. Physical function (SF-36) averaged 72 1 year after surgery. All operated
      patients had resolution of infection. There was neither migration of mesh cage
      nor posterior instrumentation failure at the last follow-up observation.
      CONCLUSION: The present study showed that radical debridement of spinal infection
      and anterior insertion of titanium cage, filled with autogenous bone graft,
      secured with pedicle screw instrumentation should have had a beneficial influence
      on the eradication of infection, segmental and global spinal reconstruction and
      fusion. Supplementary posterior minimal invasive pedicle screw fixation
      eliminates posterior soft tissue injury and preserves blood supply, and reduces
      surgical time, blood loss, and surgical complications.

PMID- 18827681
TI  - Locomotor training for walking after spinal cord injury.
AB  - STUDY DESIGN: Systematic review. OBJECTIVE: To assess the effects of locomotor
      training on improvement in walking for people with traumatic spinal cord injury
      (SCI). METHODS: We searched the Cochrane Injuries Group Specialized Register
      (last searched June 2007); the Cochrane Central Register of Controlled Trials
      (The Cochrane Library 2007, Issue 2); MEDLINE (1966-June 2007); EMBASE (1980-June
      2007); National Research Register (2007, Issue 2); CINAHL (1982-June 2007);
      Allied and Complementary Medicine Database (1985-June 2007); SPORTDiscus (1949
      June 2007); the Physiotherapy Evidence database (searched June 2007); COMPENDEX
      (engineering databases) (1972-June 2007); INSPEC (1969- June 2007); and the
      National Research Register, Zetoc, and Current Controlled Trials research and
      trials registers. We also handsearched relevant conference proceedings, checked
      reference lists, and contacted study authors in an effort to identify published,
      unpublished and ongoing trials.We included randomized controlled trials (RCT)
      that compared locomotor training to any other exercise provided with the goal of
      improving walking function after SCI or to a no-treatment control group. Two
      review authors independently selected trials for inclusion, assessed trial
      quality and extracted the data. The primary outcomes were walking speed and
      walking capacity at follow-up. RESULTS: Four RCTs involving 222 patients were
      included in this review. Overall, the results were inconclusive. There was no
      statistically significant effect of locomotor training on walking function after
      SCI comparing bodyweight supported treadmill training with or without functional
      electrical stimulation or robotic-assisted locomotor training. CONCLUSION: There
      is insufficient evidence from RCTs to conclude that any 1 locomotor training
      strategy improves walking function more than another for people with SCI.
      Research in the form of large RCTs is needed to address specific questions about
      the type of locomotor training which might be most effective in improving walking
      function of people with SCI.

PMID- 18827682
TI  - Reference data for in vivo magnetic resonance imaging properties of meniscoids in
      the cervical zygapophyseal joints.
AB  - STUDY DESIGN: Prospective in vivo study of meniscoids in the cervical
      zygapophyseal joints. OBJECTIVE: To generate reference data for in vivo magnetic
      resonance (MR) imaging properties of meniscoids in the cervical zygapophyseal
      joints. SUMMARY OF BACKGROUND DATA: Meniscoids, also called synovial folds, are
      tiny anatomic structures within the zygapophyseal joints. It has been suggested
      that pathologic conditions of meniscoids may be a potential source of cervical
      pain. Prior studies were limited to in vitro observations. To identify pathologic
      conditions of the meniscoids, it is necessary to obtain reference data of basic
      in vivo MR imaging properties of meniscoids in a healthy population. METHODS:
      Fifty-six healthy volunteers (33 women, 23 men; mean age 42.0 +/- 17.1 years)
      were investigated in a 3.0 Tesla MR scanner using high resolution isotropic 3
      dimensional sequences. Presence, size, location, and signal intensity of the
      meniscoids were assessed, and their dependence on sex, age, body mass index, and
      degenerative changes were analyzed by t test and correlation analysis. RESULTS:
      There was no significant difference in presence (20.3 +/- 4.8 vs. 19.7 +/- 4.8)
      and size (3.8 +/- 0.7 mm vs. 4.1 +/- 0.5 mm) of meniscoids between women and men.
      Presence of meniscoids decreased with increasing age (r = -0.38, P = 0.004). Size
      of meniscoids did not significantly depend on age (r = 0.02, P = 0.91). Meniscoid
      entrapment (location) was a rare condition (0.4%). Tissue composition (signal
      intensities) of the meniscoids was 61.6% mainly fatty, 15.8% mainly fibrous, and
      22.6% mixed. CONCLUSION: Basic data about in vivo MR imaging properties of
      cervical meniscoids in a healthy population have been successfully generated.
      Subsequent studies may use these data as reference for the identification of
      meniscoid pathologies.

PMID- 18827683
TI  - Patient activation and adherence to physical therapy in persons undergoing spine
      surgery.
AB  - STUDY DESIGN: Prospective longitudinal study. OBJECTIVE: To determine the
      association between baseline patient activation and participation in
      postoperative physical therapy in a cohort of individuals after lumbar spine
      surgery. SUMMARY OF BACKGROUND DATA: The Patient Activation Measure is a recently
      developed tool to assess patient activation. Patient activation is defined as an
      individual's propensity to engage in adaptive health behavior that may, in turn,
      lead to improved patient outcomes. It has not previously been used in spine
      research. METHODS: We assessed baseline patient activation levels in individuals
      presenting for surgery of the lumbar spine via the Patient Activation Measure.
      Differences in patient characteristics across patient-activation quartiles were
      assessed using analysis of variance. After surgery, we assessed attendance (self
      reported weekly) and engagement in physical therapy (at the last visit, using the
      Hopkins Rehabilitation Engagement Rating Scale) and determined the ratio of
      sessions attended to sessions prescribed. The influence of baseline patient
      activation, in the setting of other patient characteristics, to predict
      attendance and engagement with physical therapy was examined using linear
      regression methods. RESULTS: Scores on the Patient Activation Measure were
      positively correlated with participation (r = 0.53) and engagement (r = 0.75) in
      physical therapy. Individuals with low activation were more likely to report low
      self-efficacy for physical therapy, low hope, and external locus of control
      compared with those with high activation. CONCLUSION: Increased patient
      activation is associated with improved adherence with physical therapy as
      reflected in attendance and engagement.

PMID- 18827684
TI  - Spinal cord injury without radiological abnormality in an infant with delayed
      presentation of symptoms after a minor injury.
AB  - STUDY DESIGN: We present a very rare case of an infant with delayed presentation
      of spinal cord injury without radiologic abnormality (SCIWORA) after a minor
      injury. OBJECTIVE: To emphasize the importance of spinal evaluation with MRI in
      selected cases, even after minor injuries, especially in infants. SUMMARY OF
      BACKGROUND DATA: SCIWORA arises mainly in infants and children during accidental
      trauma or after sport injury. However, it has been very rare for a 6-day-delayed
      infant SCIWORA after a minor injury. METHODS: An infant presented with transient
      nausea and vomiting after falling from a baby-rocking horse of less than 30-cm
      height. The patient demonstrated right hemiparesis 6 days later. Plain cervical
      radiographs and brain and cervical spine computed tomograms (CT) were normal, but
      the cervical magnetic resonance imaging (MRI) demonstrated a high signal in the
      T2-weighted image of the lower cervical cord, and a neck collar was applied.
      RESULTS: A follow-up cervical MRI 1 month later showed that the high signal of
      the lower cervical cord had disappeared. Another follow-up cervical MRI 12 months
      later also showed normal radiographic findings but there still remained mild
      weakness of the right lower extremities. CONCLUSION: The authors present a rare
      case of infant SCIWORA who developed delayed neurologic symptoms 6 days after a
      minor injury and suggest that spinal evaluation with MRI could be warranted in
      the selected case even after minor injuries, especially in infants.

PMID- 18827685
TI  - Lumbar epidural capillary hemangioma presenting as lumbar disc herniation
      disease: case report.
AB  - STUDY DESIGN: A case of lumbar spinal epidural hemangioma is presented.
      OBJECTIVE: To present the first reported lumbar spinal epidural hemangioma
      patient clinically mimicking the lumbar disc herniation disease. SUMMARY OF
      BACKGROUND DATA: Capillary hemangiomas are benign endothelial cell neoplasms that
      are believed to be hamartomatous proliferations of vascular endothelial cells.
      The occurrence of spinal epidural capillary hemangiomas is exceedingly rare.
      There are only 3 reported epidurally located cases of capillary hemangiomas in
      the spinal channel in literature. Lumbar spinal epidural capillary hemangioma in
      a patient has not been previously reported. METHODS: Radiologic features,
      pathology, and clinical course were documented. RESULTS: L4 hypoesthesia and back
      pain of the patient was caused by an epidurally located capillary hemangioma. The
      neurologic symptoms of the patient were markedly improved after surgery.
      CONCLUSION: We have reported for the first lumbar epidural capillary hemangioma
      patient in literature. These lesions are benign and surgical treatment is
      curative.

PMID- 18827686
TI  - Spinal neurocutaneous melanosis without cutaneous nevi.
AB  - STUDY DESIGN: A case report of spinal neurocutaneous melanosis without cutaneous
      nevi. OBJECTIVE: To show a case and review the epidemiology, diagnosis and
      treatment of neurocutaneous melanosis without cutaneous nevi. SUMMARY OF
      BACKGROUND DATA: Neurocutaneous melanosis is a rare congenital syndrome
      consisting of benign or malignant melanocytic tumors of the central nervous
      system and cutaneous nevi. Symptomatic neurocutaneous melanosis has extremely
      poor prognosis, even in the absence of malignancy. Because leptomeningeal lesions
      of the neurocutaneous melanosis usually undergo malignant transformation, the
      life expectancy of almost all patients with malignant transformation is <1 year.
      In general, patients are treated with palliative therapy, such as shunt placement
      to reduce intracranial pressure or tumor resection to reduce compression of the
      brain or spine. METHODS: A 29-year-old man presented with marked hypesthesia and
      spastic gait. No skin abnormalities were evident. Magnetic resonance imaging
      (MRI) of the spine revealed intradural tumor at the T5 level. Computed tomography
      myelography showed intradural extramedullary tumor. Because symptoms progressed,
      he underwent surgery to decompress the spinal cord. After the pigmented dura was
      opened, a pigmented tumor was resected. RESULTS: Histologically, the pigmented
      tumor represented low grade. The pigmented dura and bone comprised melanin
      bearing cells without tumor cells. Meningeal melanocytoma with leptomeningeal
      melanosis in the absence of cutaneous nevi was diagnosed. Neurologic symptoms
      recovered immediately after surgery. No evidence of local recurrence has been
      seen after 3 years. CONCLUSION: This patient displayed spinal meningeal
      melanocytoma and leptomeningeal melanosis without cutaneous nevi. The diagnosis
      in this case was speculated to represent a forme fruste of neurocutaneous
      melanosis.

PMID- 18827687
TI  - Dislodged upper thoracic cage in the gastrointestinal tract: a case report and
      literature reviews.
AB  - STUDY DESIGN: A rare case of esophageal perforation secondary to a dislodged
      upper thoracic cage found by the gastrointestinal endoscope is presented.
      OBJECTIVE: To report an extremely rare complication of upper thoracic vertebral
      tuberculosis treated with corpectomy and interbody cage surgery and suggest the
      cause, mechanism, and outcome of the complication of esophageal perforation.
      SUMMARY OF BACKGROUND DATA: Tuberculotic spondylitis often affects the anterior
      column of the spine and surgery is indicated in the presence of an epidural
      abscess, neurologic deficits secondary to compression of the spinal cord, bone
      destruction with instability, or failure of antituberculous therapy. Surgical
      treatment requires radical debridement followed by anterior stabilization. A
      controversy exists regarding the use of the instrumentation in the tuberculous
      spine. METHODS: Retrospective case study and literature review. RESULTS: Because
      of the concomitant medical problems and little deterioration of the neurologic
      function, our patient is managed uneventfully with conservative treatment.
      CONCLUSION: To the authors' knowledge, this is an extremely rare reported
      complication of upper thoracic cage surgery for vertebral tuberculosis. This case
      demonstrates that the cage migration in the tuberculous spondylitis might have a
      rather benign clinical course and structural bone grafting or interbody cage
      insertion without supplemental instrument fixation seems to be inadequate.

PMID- 18827688
TI  - Isolated neurolymphomatosis of the cauda equina and filum terminale: case report.
AB  - STUDY DESIGN: Case report. OBJECTIVE: We report the case of a previously healthy
      16-year-old boy who presented with back pain and decreased mobility. Magnetic
      resonance imaging (MRI) revealed an extensive intradural lesion in the region of
      the thoracolumbar junction. SUMMARY OF BACKGROUND DATA: Neurolymphomatosis is a
      rare but well-described entity in which malignant lymphocytes, more commonly of B
      cell lineage, infiltrate the peripheral nervous system. Isolated involvement of
      spinal nerve roots and subsequent clinical presentation directly due to this is
      unusual, and there have been few such published cases. METHODS: Retrospective
      case study with follow-up examination at 6-months and 1-year. RESULTS: The
      patient was transferred directly to the operating theater from MRI for urgent
      decompressive laminectomy. Diagnosis of neurolymphomatosis of the cauda equina
      and filum terminale by diffuse large B-cell lymphoma was confirmed by
      histopathology. The patient received adjuvant chemotherapy and radiotherapy. At 6
      and 12-month follow-up, the patient's back pain had resolved and lower limb
      function was improving slowly. MRI revealed no evidence of residual or recurrent
      disease. CONCLUSION: This case highlights the importance of prompt diagnosis
      through high-resolution imaging, as well as the role of emergent neural
      decompression once a diagnosis of spinal cord compression has been established
      (regardless of the ultimate cause). It exposes some of the diagnostic pitfalls
      associated with the imaging of unusual spinal lesions, and it underlines the
      importance of obtaining an urgent and accurate tissue diagnosis to allow for the
      instigation of appropriate medical therapy.

PMID- 18827690
TI  - Urgent surgical decompression compared to methylprednisolone for the treatment of
      acute spinal cord injury: a randomized prospective study in beagle dogs.
AB  - STUDY DESIGN: Experimental dog model of acute spinal cord injury. OBJECTIVE: To
      compare the relative value of methylprednisolone, surgical decompression, or both
      for the treatment of traumatic spinal cord injury. SUMMARY OF BACKGROUND DATA:
      Acute spinal cord injury results from both primary damage to the spinal cord at
      the time of the initial injury as well as a deleterious secondary cascade of
      events, which leads to further damage. Surgical decompression is known to improve
      clinical outcomes, but the timing of surgical decompression remains
      controversial. METHODS: A nylon tie was used to constrict the spinal cord in 18
      adult male beagle dogs. The animals were then prospectively randomized to 3
      groups: 1) surgical decompression at 6 hours and intravenous methylprednisolone;
      2) surgical decompression at 6 hours and intravenous saline; and 3) intravenous
      methylprednisolone without surgical decompression. Each animal was evaluated by
      somatosensory-evoked potentials, daily neurologic assessment, and histologic
      examination at 2 weeks following injury. RESULTS: Immediately following spinal
      cord constriction, all animals were paraplegic, incontinent, and the
      somatosensory-evoked potentials were abolished. Surgical decompression 6 hours
      after injury, with or without methylprednisolone, led to significantly better
      neurologic function at 2 weeks than methylprednisolone alone. CONCLUSION: In the
      setting of acute and persistent spinal cord compression in beagle dogs, surgical
      decompression 6 hours after injury, with or without methylprednisolone, is more
      effective for improving neurologic recovery than methylprednisolone alone.

PMID- 18827691
TI  - Neuroprotective effects of caspase-3 inhibition on functional recovery and tissue
      sparing after acute spinal cord injury.
AB  - STUDY DESIGN: We used gene microarrays and found that caspase-related death genes
      were upregulated. We tested caspase inhibition and evaluated its effect on the
      spinal cord after traumatic injury. OBJECTIVE: The logical extension of previous
      studies was to determine whether downstream CASP genes might also be involved and
      whether inhibition might prevent injury-induced cell death. SUMMARY OF BACKGROUND
      DATA: Apoptotic cell death occurs in all endogenous cellular compartments of the
      spinal cord, peaking at 3 days after injury in neurons, astrocytes, and
      microglia. The downstream effector caspase-3 cleaves several important cellular
      sites after being activated by upstream initiator caspases. Along with others, we
      have previously identified caspase signature cleavage of PARP, alpha-fodrin, and
      DFF45/ICAD in the injured rat spinal cord. We also showed rapid upregulation of
      caspase-3 gene expression along with localization of active caspase-3 in neurons
      and activated microglia after SCI. Others have reported that a more general
      active-site mimetic peptide ketone, benzylocarbonyl-Val-Ala-Asp-fluromethylketone
      (zVAD-fmk) was neuroprotective after rat spinal cord injury (SCI). METHODS: In
      this study, we administered the caspase-3 subfamily tetrapeptide cell permeable
      inhibitor Z-Asp(O-Me)-Glu(O-Me)-Val-Asp(O-Me) fluoromethyl ketone (DEVD-fmk)
      intraperitoneally 1 hour after laminectomy and moderate (25 g cm force) SCI in
      rats. RESULTS.: We used the open field locomotor rating (LRS) over a 14-day
      course and found statistically significant improvement in DEVD-fmk-treated rats,
      LRS, 9.8 +/- 0.93 SEM, compared with vehicle, 6.6 +/- 0.4 (P < 0.05). Histologic
      analysis of percent spinal cord tissue volume spared was 50% greater for DEVD-fmk
      versus control (P < 0.5). CONCLUSION: These results indicate neuroprotection at
      both the cellular level and with substantial functional recovery, suggesting
      caspase-3 inhibition may be a viable therapy in the early hours after
      experimental SCI.

PMID- 18827692
TI  - Indications for cervical pedicle screw instrumentation in nontraumatic lesions.
AB  - STUDY DESIGN: Retrospective clinical study. OBJECTIVE: To evaluate clinical
      results of patients with nontraumatic cervical lesions treated by cervical
      pedicle screw (PS) fixation and to discuss the surgical indications. SUMMARY OF
      BACKGROUND DATA: PS fixation provides an outstanding stability for cervical
      lesions with instability. This technique, however, has a potential risk of
      vertebral artery, spinal cord, and nerve root injuries, which may be
      catastrophic. METHODS: Fifty-eight patients were divided into 2 groups: patients
      with cervical kyphosis with vertebral destructive lesions (group D, n = 38) and
      those without destructive lesions (group ND, n = 20). Clinical results of the 2
      groups were compared. The results of decompression and PS fixation for cervical
      spondylotic myelopathy (CSM) and ossification of the posterior longitudinal
      ligament (OPLL) in this series were also compared with those of previous
      laminoplasty alone in patients with CSM and OPLL. RESULTS: Nape pain in group D
      improved in 86.7% of the patients. Overall neurologic status was improved in both
      groups. Bony fusion was confirmed in 100% of the cases that were alive in group D
      and 95% in group ND. Eight complications including 2 vertebral artery injuries
      occurred. The incidence of postoperative cervical complications in group ND was
      significantly higher than that in group D. Although PS fixation significantly
      corrected cervical kyphosis and maintained in both CSM and OPLL, operation time
      and intraoperative blood loss in cases treated by PS were significantly higher
      than those treated by laminoplasty alone. Improvement of nape pain and neurologic
      status did not differ with and without using PS fixation. CONCLUSION: There is an
      indication of cervical PS fixation for destructive lesions because of a high
      fusion rate with improvement of nape pain. On the other hand, there is no
      indication in cases of typical CSM and OPLL if a potential risk of vertebral
      artery or nerve injury is taken into account.

PMID- 18827693
TI  - Iron oxide nanoparticles significantly enhances the injectability of apatitic
      bone cement for vertebroplasty.
AB  - STUDY DESIGN: Experimental study to characterize the setting and the
      cytocompatibility properties of apatitic bone cement. OBJECTIVE: To investigate
      the setting, flowing, and biocompatibility properties of new iron-modified
      calcium phosphate bone cements. SUMMARY OF BACKGROUND DATA: Vertebroplasty and
      kyphoplasty are efficient procedures for the treatment of painful vertebral
      compression fractures. Nowadays, calcium phosphate cements are used to treat
      these fractures mainly due to the similar bone apatitic phase formed after
      setting. However, clinicians have reported great difficulties in filling the
      vertebral bodies due to the high pressures needed to inject these materials.
      Thus, new approaches are needed to improve the initial flowing properties of
      these cements without affecting or even improving their short-term mechanical
      stability and their long-term in vivo cement transformation into bone tissue.
      METHODS: Cement setting times were measured by the Gillmore needles method. The
      evolution of the compressive strength accounted for the cement hardening process.
      Scanning Electron Microscopy followed the evolution of the cement microstructure
      with hardening. Radiograph diffraction analysis confirmed the evolution of the
      crystalline phases underlying the setting and the hardening processes.
      Injectability tests were performed by using syringes filled with bone cement and
      recording the evolution of the injection force needed to empty the syringe.
      Finally, the cytocompatibility was analyzed by culturing human epithelial cells
      onto the cements and evaluating both the relative cell viability and the adhesion
      cell density. RESULTS: The modification of the powder phase of an alpha
      tricalcium phosphate cement with iron oxide nanopar-ticles significantly
      enhanced, at constant liquid to powder cement mixing ratio, the resulting cement
      injectability by lowering the extrusion force required for cement delivery. For
      example, 24 wt% iron oxide addition resulted in 83% of cement injected with an
      extrusion force lower than 25 N. In fact, the setting and the working times of
      the cement pastes increased with iron oxide addition. Moreover, the new cement
      pastes showed improved compressive strength in agreement with the crystalline
      microstructure evolved during hardening. However, iron modification did not
      produced cytotoxic cements as compare to nonmodified cements. CONCLUSION: It has
      been shown that the addition of iron oxide nanoparticles into the powder phase of
      an alpha-tricalcium phosphate based cement improved both, the initial
      injectability and maximum compressive strength of the cement without affecting
      their physico-chemical setting reactions and their cytocompatibility. These
      results could be further exploited by designing improved injectable apatitic
      cements with suitable mechanical properties and in vivo cement transformation
      ratios into bone tissue by incorporating phases creating porosity.

PMID- 18827695
TI  - Antibiotic-loaded allograft decreases the rate of acute deep wound infection
      after spinal fusion in cerebral palsy.
AB  - STUDY DESIGN: A retrospective matched cohort study with control group. OBJECTIVE:
      To compare the infection rate after posterior spinal fusion with unit rod
      instrumentation with or without gentamicin-impregnated allograft bone in children
      with cerebral palsy (CP). SUMMARY OF BACKGROUND DATA: Previous studies evaluating
      wound infection rates after spinal fusion surgery in children with CP report an
      8.7% to 10% wound infection rate. The concept of using antibiotic-loaded bone
      graft (AbBGF) to provide local antibiotics has been explored in high risk
      patients, such as those with osteomyelitis or infected joint arthroplasty. There
      have been no reports of using AbBGF prophylactically in spine surgery. METHODS:
      After IRB approval, the medical records of 220 children with CP who underwent
      spinal fusion with unit rod instrumentation for a primary spinal deformity
      between January 2000 through December 2006 at a single institution were
      retrospectively reviewed. We evaluated the incidence of postoperative wound
      infection in patients with AbBGF and those without bone graft (BGF). RESULTS: One
      hundred fifty-four patients received AbBGF during spinal fusion surgery and 6
      patients (3.9%) developed a deep wound infection. Ten (15.2%) of the 66 patients
      without AbBGF developed a deep wound infection. The difference between groups was
      statistically different (P = 0.003). The mean age at surgery, preoperative Cobb
      angle, correction rate, operative time, and estimated blood loss were not
      statistically different between the 2 groups (P > 0.05). The length of hospital
      stay was decreased in the AbBGF group (P < 0.05). CONCLUSION: The incidence of
      deep wound infection after spinal fusion in 220 children with CP scoliosis
      decreased from 15% to 4% with the use of prophylactic antibiotics in the
      corticocancellous allograft bone.

PMID- 18827696
TI  - The use of traction in the treatment of severe spinal deformity.
AB  - STUDY DESIGN: Multicenter, retrospective, nonrandomized comparison group study of
      patients with severe scoliosis and kyphosis treated after 1995 with halo-gravity
      traction and without halo-gravity traction before definitive fusion. OBJECTIVE:
      Compare surgical correction of severe spine deformity with preoperative halo
      traction and without preoperative traction. SUMMARY OF BACKGROUND DATA: Prior
      studies have demonstrated that halo traction is a safe, well-tolerated method of
      applying gradual, sustained traction to maximize operative correction in patients
      with severe idiopathic scoliosis (IS) and kyphosis. However, these studies lack a
      comparison control group and study only a relatively small number of patients
      with IS. METHODS: Fifty-three patients with severe scoliosis or kyphosis were
      studied using hospital records, standing preoperative, traction, postoperative,
      and final radiographs. Thirty were treated with traction and 23 were treated
      without traction. Patients within each group were analyzed based on demographics,
      diagnosis, perioperative, and radiographic data. In addition, patients were
      evaluated based on diagnosis, specifically whether patients had adolescent
      idiopathic scoliosis. RESULTS: Within the entire study population, there was no
      statistically significant difference in main coronal curve correction (62% vs.
      59%), operative time, blood loss, and total complication rate (27% vs. 52%).
      However, the nontraction group underwent vertebral column resection more often
      (30% vs. 3%, P = 0.015). The traction group had a statistically significant
      increase in average hospital stay (36 vs. 14 days) (P = 0.011). Analysis of the
      23 patients with adolescent idiopathic scoliosis also showed no statistically
      significant differences in curve correction, blood loss, or complications.
      CONCLUSION: Our study shows that patients with halo traction less frequently had
      a vertebral body resection, but achieved comparable deformity correction.

PMID- 18827697
TI  - Blood conservation techniques in spinal deformity surgery: a retrospective review
      of patients refusing blood transfusion.
AB  - STUDY DESIGN: A retrospective review. OBJECTIVE: To review the effectiveness of
      blood conservation techniques in the spinal fusion of patients that refuse blood
      transfusion; specifically the Jehovah's witnesses population. SUMMARY OF
      BACKGROUND: Spinal surgery can be challenging in patients refusing blood
      transfusion. There is paucity in the literature examining blood conservation
      techniques in spinal surgery. METHODS: The radiographic and medical records of 19
      Jehovah's witnesses patients who underwent spinal deformity surgery at a single
      institution between 2000 and 2003 were reviewed. Patients were assessed for
      excessive blood loss (EBL), deformity correction, operative time, perioperative
      complications, and hospital stay. At latest follow-up (mean, 40 months; range, 8
      76) the patients were examined for radiographic fusion, progression and
      complications. RESULTS: Spinal fusion was attempted in 19 patients, with a mean
      age of 17 years (range, 10-36 years). All 19 patients were identified through the
      "Bloodless Surgery Program." Hypotensive anesthesia, hemodilution, and cell saver
      was employed for all 19 cases. Erythropoietin with supplemental iron was used in
      15 patients. Aprotinin was used in 3 patients. EBL and blood returned by cell
      saver averaged 855 and 341 mL, respectively. Operative times average 315 minutes.
      The average drop in hemoglobin from after surgery was 3.1 g/dL. There were 2
      intraoperative complications: (i) transient loss of somatosensory evoked
      potential/motor evoked potential signals; and (ii) one surgery abandoned due to
      EBL. The average spinal deformity correction was 58%. There were 3 postoperative
      complications, none related to their refusal of a transfusion. 17 patients were
      available for radiographic and clinic follow-up of at least 24 months. All
      displayed radiographic fusion without progression. CONCLUSION: These blood
      conservation techniques allow satisfactory completion of deformity surgery on
      those patients not willing to be transfused and without major anesthetic or
      medical complications.

PMID- 18827698
TI  - Postural model of sagittal spino-pelvic alignment and its relevance for
      lumbosacral developmental spondylolisthesis.
AB  - STUDY DESIGN: Comparative study of sagittal spino-pelvic alignment in children
      and adolescents with developmental lumbosacral spondylolisthesis compared with
      asymptomatic subjects. OBJECTIVE: To develop a global postural model of sagittal
      spino-pelvic alignment. SUMMARY OF BACKGROUND DATA: The relationships between
      parameters of sagittal spino-pelvic alignment in developmental spondylolisthesis
      are still unclear. METHODS: Radiographs of 120 control subjects and 131 subjects
      with developmental spondylolisthesis (91 low-grade, 40 high-grade) were reviewed.
      Subjects with high-grade spondylolisthesis were divided according to their sacro
      pelvic alignment: balanced versus retroverted sacro-pelvis. Parameters of the
      sacro-pelvis (pelvic incidence, pelvic tilt, sacral slope), lumbosacral region
      (lumbosacral angle, slip percentage), lumbar spine (lumbar lordosis, lumbar
      tilt), thoracic spine (thoracic kyphosis, thoracic tilt), and global balance
      (spinal tilt, sagittal offset between C7 and femoral heads) were assessed.
      Parameters were compared between all groups and a correlation study was performed
      between all parameters. A postural model that includes the measured parameters
      was used to analyze the obtained correlations. RESULTS: Significant differences
      in all parameters are found between all groups, except for sagittal offset. The
      pattern and strength of correlations is similar between normal and low-grade
      subjects, showing interdependence between sacro-pelvic, lumbosacral, lumbar, and
      thoracic regions. The pattern of relationships was altered in high-grade
      spondylolisthesis, especially for subjects with a retroverted sacro-pelvis for
      which correlations between pelvic incidence and pelvic tilt, and between the
      sacro-pelvic unit and lumbar spine geometry are lost. CONCLUSION: Children and
      adolescents stand with a relatively constant global sagittal spino-pelvic
      alignment, regardless of the local lumbosacral deformity. A normal posture is
      maintained in low-grade spondylolisthesis and in high-grade spondylolisthesis
      with a balanced sacro-pelvis. Posture is abnormal in high-grade spondylolisthesis
      associated with a retroverted sacro-pelvis, suggesting that surgical reduction of
      the local lumbosacral deformity in these patients could be attempted to restore a
      normal posture.

PMID- 18827699
TI  - Dynamic angular three-dimensional measurement of multisegmental thoracolumbar
      motion in vivo.
AB  - STUDY DESIGN: Method validation and in vivo motion segment study. OBJECTIVE: To
      determine in healthy subjects in vivo intervertebral segmental kinematics and
      coupled motion behavior in all 3 planes simultaneously for 3 segments and to
      evaluate whether these results differ from those in the normal population
      according to the literature. SUMMARY OF BACKGROUND DATA: Few studies have
      provided a direct invasive approach to investigate segmental kinematics in vivo.
      Dynamic recordings of 3-dimensional segmental motion patterns of adjacent
      segments have rarely been reported. To date, no studies have examined the 3
      dimensional segmental movements of the thoracolumbar junction in vivo in detail.
      METHODS: K-wires were inserted into the Th11, Th12, L1, and L2 spinous processes
      of 21 healthy subjects. Ultrasound markers and sensors were attached to the k
      wires. Real-time motion data were recorded during standardized ranging exercises.
      Errors caused by the k-wires, and the static and dynamic accuracy of the system,
      were considered. RESULTS: Large intersubject variation was found in all of the
      exercises. The average ranges of motion from Th11 to L2 were 18.7 degrees for
      flexion-extension, 13.5 degrees for one-sided lateral bending, and 1.8 degrees
      for one-sided axial rotation. Coupled-motion patterns among the subjects showed a
      coupled flexion in active lateral bending and a coupled extension in active
      rotation, but the results were inconsistent for active extension and flexion.
      CONCLUSION: This method offered accurate multisegmental dynamic-recording
      facilities. The dynamic exercises showed high reproducibility. The ranges of
      motion for extension/flexion and lateral bending differed from those reported in
      previous studies. The coupling patterns were only partly consistent because of
      large interindividual variation. The measurement error was comparable with that
      of other invasive methods.

PMID- 18827700
TI  - Changes in physical function after palliative surgery for metastatic spinal
      tumor: association of the revised Tokuhashi score with neurologic recovery.
AB  - STUDY DESIGN: A retrospective study of patients undergoing palliative surgery for
      metastatic spinal tumors. OBJECTIVE: To investigate short-term functional
      recovery and duration of improvement after palliative surgery, to correlate these
      outcomes with the revised Tokuhashi score, and to examine the relationship
      between function and neurologic deterioration. SUMMARY OF BACKGROUND DATA: The
      revised Tokuhashi score is a scoring system used to predict life expectancy for
      patients with metastatic spinal tumors. The relationship between the revised
      Tokuhashi score and physical functional improvement after palliative surgery has
      not been examined previously. METHODS: The clinical charts of 86 patients were
      reviewed. The Eastern Cooperative Oncology Group Performance Status (ECOG-PS) was
      used to assess physical function. Each score was documented before surgery and at
      every month after surgery. The duration of ECOG-PS improvement, defined as the
      period between surgery and deterioration to the preoperative ECOG-PS grade, was
      correlated with the revised Tokuhashi score. RESULTS: The ECOG-PS grade improved
      in 44 (51.1%) patients at 1 month postoperative. When ECOG-PS improvement was
      found after surgery, it persisted above the preoperative level for an average of
      9.3 months. At 1 month postoperative, patients scoring 0 to 8 on the total
      revised Tokuhashi score had significantly lower ECOG-PS improvement (26 of 55
      patients) when compared to patients with higher scores (18 of 27 patients, P <
      0.05). In 44 patients with ECOG-PS improvement, the existence of major internal
      organ metastases significantly shortened the duration of improvement (P < 0.05).
      CONCLUSION: Palliative surgery benefited half of the patients with metastatic
      spinal tumor, with a greater probability of benefit found in persons with a
      higher total revised Tokuhashi score (score 9-15) and/or primary cancers with
      longer survival times.

PMID- 18827701
TI  - Reliability, validity, and responsiveness of the Norwegian versions of the Maine
      Seattle Back Questionnaire and the Sciatica Bothersomeness and Frequency Indices.
AB  - STUDY DESIGN: Cross-sectional and prospective study of patients with sciatica and
      disc herniation. OBJECTIVE: To describe the process of translation of the
      Norwegian versions of the Maine Seattle Back Questionnaire (MSBQ), the Sciatica
      Bothersomeness Index (SBI) and the Sciatica Frequency Index (SFI), and to test
      the reliability, construct validity and responsiveness of these Norwegian
      versions. SUMMARY OF BACKGROUND DATA: The instruments have been validated in
      English only. METHODS: Reliability was assessed by internal consistency (Cronbach
      alpha), test-retest reliability (ICC) and measurement error (MDC and Bland and
      Altman's limits of agreement). Construct validity was assessed by comparing the 3
      measures with subscales of SF-36, ratings of back and leg pain, and clinical
      findings. Responsiveness was assessed by standardized response means and Receiver
      Operating Characteristic curve analyses. RESULTS: Four hundred sixty six patients
      were included in the study, of whom 87 participated in the test-retest study.
      Completion time for the MSBQ was 1-2 minutes and 30 seconds for the SBI and the
      SFI, respectively. ICCs varied between 0.86 and 0.90. Cronbach alpha was 0.74,
      0.70, and 0.65 for the MSBQ, SBI, and SFI, respectively. The measurement errors
      constituted 26% of the total MSBQ score range, 22% of the SBI and 27% of the SFI
      score range. Compared to the MSBQ the 2 Sciatica Indexes discriminated better
      between patients with normal versus abnormal clinical findings, but correlated
      less strongly with pain and physical functioning. Responsiveness was assessed by
      2 external criteria at 3 months, a global change score (improved vs. unchanged)
      and surgical treatment status (operated vs. nonoperated). All standardized
      response means were >or=1.3 and all AUCs >or=0.75. Differences between the 3
      measures were generally small. CONCLUSION: The Norwegian versions of the MSBQ and
      the Sciatica Frequency and Bothersomeness Indexes were rapidly administered, with
      acceptable internal consistency, test-retest reliability, measurement error,
      construct validity and responsiveness.

PMID- 18827702
TI  - Development of a Chinese version of the Oswestry Disability Index version 2.1.
AB  - STUDY DESIGN: Cross-cultural adaptation and cross-sectional psychometric testing
      in a convenience sample of patients with low back pain. OBJECTIVE: To translate
      and culturally adapt the Oswestry Disability Index version 2.1 (ODI 2.1) into a
      Mandarin Chinese version and to assess its reliability and validity. SUMMARY OF
      BACKGROUND DATA: The Chinese ODI 2.1 has not been developed and validated.
      METHODS: The ODI 2.1 was translated and culturally adapted to the Chinese
      version. The validity of the translated Chinese version was assessed by examining
      the relationship between the ODI and other well-known measures. Test-retest
      reliability was examined in 52 of these patients, who completed a second
      questionnaire within 1 week. RESULTS: Internal consistency of the ODI 2.1 was
      excellent with Cronbach's alpha = 0.903. The intraclass correlation coefficient
      of test-retest reliability was 0.89. The minimal detectable change was 12.8. The
      convergent validity of the Chinese ODI is supported by its high correlation with
      other physical functional status measures (Roland Morris Disability Questionnaire
      and SF-36 physical functioning subscale, r = 0.76 and -0.75, respectively), and
      moderate correlation with other measures (Visual Analogue Scale, r = 0.68) and
      certain SF-36 subscales (role-physical, bodily pain, and social functioning, r
      range: -0.49 to -0.57). As expected, the ODI was least correlated with
      nonfunctional measures (SF-36 mental subscale and role-emotional subscale, r = 
      0.25 and -0.33, respectively). CONCLUSION: The results of this study indicate
      that the Chinese version of the ODI 2.1 is a reliable and valid instrument for
      the measurement of functional status in patients with low back pain.

PMID- 18827703
TI  - Occipitocervical fusion using recombinant human bone morphogenetic protein-2:
      adverse effects due to tissue swelling and seroma.
AB  - STUDY DESIGN: Case presentation and literature review. OBJECTIVE: To review the
      safety of using INFUSE bone graft (recombinant human bone morphogenetic protein-2
      applied to an absorbable collagen sponge) in occipitocervical (OC) fusion.
      SUMMARY OF BACKGROUND DATA: Although INFUSE bone graft is currently approved for
      use in certain tibial fractures, oral maxillary procedures, and anterior lumbar
      interbody fusion, it has been extensively used "off-label" in posterolateral
      lumbar and anterior cervical fusions. INFUSE is highly effective in promoting
      cervical spine fusion via an anterior approach, but its potential role in
      promoting bony fusion in posterior cervical or OC fixation has not been studied.
      METHODS: A 53-year-old woman with basilar invagination underwent OC fixation
      using INFUSE bone graft. Three days after surgery she experienced neurologic
      decline associated with significant tissue swelling and a large postoperative
      seroma under significant pressure. She made excellent recovery after reoperation
      and drainage. An extensive review of the literature was performed to propose a
      modified approach to the use of INFUSE in OC fixation. RESULTS: Proper dosing and
      delivery of INFUSE for posterior cervical/OC fixation is not currently known.
      Previously published experience with anterior cervical fusion suggests that
      INFUSE can have potent inflammatory effects on paraspinal soft tissue.
      CONCLUSION: INFUSE should only be used for OC fixation in patients at elevated
      risk of nonunion. To prevent complications due to soft tissue swelling,
      consideration should be given to preventing direct exposure of INFUSE to
      paraspinal musculature, prolonged soft tissue drainage, and prophylactic
      treatment with perioperative steroid therapy.

PMID- 18827704
TI  - Unknown case.

PMID- 18827706
TI  - Quantitative anatomy of subaxial cervical lateral mass: an analysis of safe screw
      lengths for Roy-Camille and Magerl techniques.

PMID- 18827712
TI  - Primary resection of late, isolated secondary GIST.

PMID- 18827713
TI  - Increased serum resistin concentration in patients with chronic pancreatitis:
      possible cause of pancreatic fibrosis.
AB  - BACKGROUND: Resistin is an adipokine, which displays proinflammatory properties.
      Thus, it is likely that resistin can influence the course of chronic
      pancreatitis, and/or that chronic pancreatitis may affect the serum resistin
      concentration. GOALS: The aim of the present study was to determine the serum
      resistin concentration in patients with chronic pancreatitis and to analyze the
      relationship between serum resistin concentration and serum concentrations of
      leptin (proinflammatory adipokine) and adiponectin (anti-inflammatory adipokine).
      STUDY: A total of 23 male, nondiabetic patients with chronic pancreatitis of
      alcoholic origin and 16 healthy subjects were examined. Fasting blood samples
      were collected from patients in both groups. Serum resistin concentration was
      assayed by enzyme-linked immunosorbent assay. Serum adiponectin, leptin, and
      insulin concentrations were determined by radioimmunoassay. RESULTS: Serum
      resistin concentration was significantly higher in patients with chronic
      pancreatitis as compared with control subjects. In contrast, patients with
      chronic pancreatitis had lower serum leptin and insulin concentrations than
      healthy subjects. There were no statistically significant differences in serum
      adiponectin concentration between patients with pancreatitis and healthy
      subjects. CONCLUSIONS: The results presented in this paper indicate that chronic
      pancreatitis in human is associated with the increase in serum resistin
      concentration and with the decrease in serum leptin and insulin concentrations.
      It can be supposed that resistin, by stimulation of tumor necrosis factor-alpha
      synthesis in blood mononuclear cells and in macrophages, increases the
      concentration of tumor necrosis factor-alpha, which in turn activates stellate
      cells. Activated stellate cells can produce collagen, eventually resulting in the
      development of pancreatic fibrosis.

PMID- 18827714
TI  - Assessment of the diagnostic value of duodenal bulb histology in patients with
      celiac disease, using multiple biopsy sites.
AB  - BACKGROUND: Multiple endoscopic biopsies from the descending duodenum are usually
      recognized as the standardized method for the evaluation of mucosal changes in
      celiac disease (CD). Generally, the duodenal bulb is not considered a useful site
      for biopsies, owing to some difficulties in histologic evaluation. GOAL: We
      wanted to verify if duodenal bulb histology establish a correct diagnosis of CD.
      STUDY: Fifty-two consecutive children with suspicion of CD and positive
      antitissue transglutaminase antibodies were enrolled in a prospective fashion.
      During upper gastrointestinal endoscopy, 2 to 4 biopsies each were taken from
      descending duodenum distal to the papilla of Vater (D2) and duodenal bulb (B).
      The histologic lesions were classified according to the modified Oberhuber
      classification by single pathologist who was blinded to the site of biopsy.
      RESULTS: A total of 52 children had a final diagnosis of CD. The main presenting
      symptoms were diarrhea 43/52 (82.7%), anemia 40/52 (76.9%), and failure to thrive
      32/52 (61.5%). All had type 3 lesion-(a) mild, (b) moderate, or (c) severe-in at
      least 1 site. There was 45/52 (86.5%) CD patients with lesions of identical type
      (type 2 or 3) in both biopsy sites. The number of intraepithelial lymphocytes was
      not significantly different in the descending part of the duodenum as compared
      with duodenal bulb. CONCLUSIONS: The biopsies from the duodenal bulb and second
      part of the duodenum in CD can be equally representative of the underlying
      disease. The diagnosis of CD can reliably be made even if biopsies are taken from
      the duodenal bulb rather than distal duodenum or jejunum.

PMID- 18827715
TI  - Rheumatic disease and complementary-alternative treatments: a qualitative study
      of patient's experiences.
AB  - BACKGROUND: Complementary-alternative medicine (CAM) has been widely used by
      rheumatic patients for many years, but doctors are often unaware of the actual
      use. OBJECTIVES: This study aimed at patients' experience and perceptions of CAM
      as a way for long-term coping with illness. METHODS: Fifteen in-depth interviews
      were conducted with patients sampled by contact with voluntary patient-driven
      rheumatic disease societies, outside of any treatment settings. Strategically,
      the sampling included a variety of rheumatic diseases and CAM-treatments, but
      strived otherwise to be typical of CAM-users. Interviews were taped and fully
      transcribed; coding and analysis of themes were assisted by computer software.
      RESULTS: Rheumatic disease patients expressed use of CAM as methods of regulation
      of discomforts, the feeling of the body, and self-empowerment, not for
      unrealistic healing of their rheumatic disease. They experienced a variety of
      effects, most often expressed in terms of mind-body interrelated experiences,
      such as "lightness of the body" rather than relief in specific symptoms. They
      expressed the feeling of "have been helped" when leaving a CAM-session and
      appreciated to have more than 1 way to understand their disease and symptoms.
      They were usually not naive, but were critical consumers. The patients typically
      believed in the alternative viewpoints of "natural is best" and in "energy
      meridians," but they were otherwise not believers in any alternative, "new age"
      type worldview. CONCLUSION: These findings suggest that clinical practice may be
      enriched by listening to or asking rheumatic disease patients' CAM-experiences in
      a nonpatronizing way.

PMID- 18827716
TI  - Genetic factors impacting therapy in acute lung injury/acute respiratory distress
      syndrome.
AB  - Acute lung injury (ALI) and its most severe form the acute respiratory distress
      syndrome occur in patients who have a predisposing severe inflammatory insult to
      the lung. Most often ALI is due to sepsis from bacterial infection, but ALI can
      occur with any infection and with noninfectious insults such as severe trauma,
      acute pancreatitis, aspiration, and near-drowning. After any of these insults,
      the interindividual risk of progression to ALI and the risk of death remain
      difficult to predict. Our inability to predict an individual's susceptibility to
      acute lung injury has long suggested that genetic factors influence ALI risk.
      There is substantial evidence for heritable predispositions to severe infections
      and an emerging body of literature implicating genetic factors in ALI
      pathogenesis. A paradigm is emerging that the genetic risk for ALI can be best
      understood in terms of factors that control 3 overlapping stages of ALI
      pathogenesis: risk for the acquisition of a predisposing condition (such as a
      severe pneumonia), risk for progression to lung injury during systemic
      inflammatory states (such as severe sepsis), and risk for failure of endogenous
      mechanisms to resolve the lung injury. The evidence supporting this paradigm is
      herein reviewed, along with potential treatment strategies that could be directed
      by knowledge of specific genetic factors in an individual patient.

PMID- 18827717
TI  - Brain imaging in pediatric obsessive-compulsive disorder.
AB  - OBJECTIVE: To review progress in understanding pediatric obsessive-compulsive
      disorder (OCD). The focus is on the frontal-striatal-thalamic model of OCD,
      neurobiological and genetic studies of the disorder, and their influence on
      recent advances in treatment. METHOD: Computerized literature searches were
      conducted with the key words "obsessive-compulsive disorder" in conjunction with
      "pediatric," "genetics," and "imaging." RESULTS: Neuroimaging studies find
      evidence to support the frontal-striatal-thalamic model. Genetic and
      neurochemical studies also implicate glutamate in the pathological finding of
      OCD. This has led to the application of glutamate-modulating agents to treat OCD.
      CONCLUSIONS: Studies of pediatric OCD have led to a refined frontal-striatal
      thalamic model of pathogenesis and are having an evidence-based impact on
      treatment. Despite this progress, fully explanatory models are still needed that
      would allow for accurate prognosis and the development of targeted and
      efficacious treatments.

PMID- 18827718
TI  - Comorbidity of psychiatric disorders and nicotine dependence among adolescents:
      findings from a prospective, longitudinal study.
AB  - OBJECTIVE: To examine prospectively the comorbidity of DSM-IV psychiatric
      disorders and nicotine dependence in adolescence. METHOD: A multiethnic sample (N
      = 1,039) of adolescents from grades 6 to 10 in the Chicago public schools (mean
      age 14.1 years) was interviewed at home five times, and mothers were interviewed
      three times over a 2-year period (2003-2005). Completion rates at each wave were
      96% of the initial sample. Selected DSM-IV psychiatric disorders were ascertained
      from youths and mothers about youths at two annual waves with the NIMH Diagnostic
      Interview Schedule for Children, Version IV-Y and IV-P; DSM-IV symptoms of
      nicotine dependence were ascertained from youths at every wave using a measure
      developed for adolescents. RESULTS: Psychiatric disorders most often preceded the
      onset of the first criterion of nicotine dependence. Prospective associations
      between psychiatric disorders and nicotine dependence were examined through
      logistic regressions. After controlling for comorbid disorders, it was found that
      lifetime disruptive disorder significantly predicted the onset of a nicotine
      dependence criterion (adjusted odds ratio 2.1). Early onset of any psychiatric
      disorder increased this risk. Other predictors included novelty seeking and
      extensiveness of smoking. By contrast, nicotine dependence did not predict the
      onset of a psychiatric disorder; significant predictors included the youths'
      prior other psychiatric disorders, novelty seeking, and parental depression and
      antisocial behavior. CONCLUSIONS: Nicotine dependence does not seem to contribute
      to the onset of psychiatric disorders, whereas disruptive disorder is an
      important etiologic factor for nicotine dependence in adolescence.

PMID- 18827720
TI  - Meta-analysis of amygdala volumes in children and adolescents with bipolar
      disorder.
AB  - OBJECTIVE: The neurophysiological basis of bipolar disorder in youths remains
      poorly understood. Neurofunctional and neuropathologic studies have implicated
      the amygdala as a primary brain structure involved in the regulation of emotion.
      Because one of the cardinal features of bipolar disorder is mood dysregulation,
      structural and functional amygdala abnormalities identified with neuroimaging may
      serve as useful disease and treatment response biomarker. Therefore, we conducted
      a meta-analysis summarizing the literature examining amygdala size obtained from
      magnetic resonance imaging in bipolar youths and adults. METHOD: A literature
      search using the National Institutes of Health's PubMed was conducted to identify
      published peer-reviewed neuroimaging studies of amygdala size in children,
      adolescents, and adults with bipolar disorder. Eleven studies that met inclusion
      and exclusion criteria were identified. RESULTS: Smaller amygdala volumes were
      found in children and adolescents with bipolar disorder compared with the control
      children and adolescents (standardized mean difference -0.74; 95% confidence
      interval -1.36 to -0.15). Amygdala volumes in bipolar adults were not
      significantly different from the control adults (standardized mean difference
      0.20; 95% confidence interval -0.31 to 0.73). CONCLUSIONS: The results of this
      meta-analysis suggest that structural amygdala abnormalities are present in
      bipolar youths but that these structural differences do not seem to be present in
      bipolar adults. Future studies examining whether structural, functional, and
      neurochemical amygdala differences between bipolar and control youths may be
      useful as age-specific biomarkers of illness and treatment response are needed.

PMID- 18827719
TI  - Integrating functional brain neuroimaging and developmental cognitive
      neuroscience in child psychiatry research.
AB  - OBJECTIVE: To provide an overview of clinical research aiming to develop a
      mechanistic understanding of brain dysfunction in child psychiatric disorders.
      METHOD: Technological, conceptual, and translational approaches relevant to the
      investigation of brain function in pediatric psychiatric illnesses are explored.
      Research in the area of pediatric bipolar disorder is used as a prototypic model
      illustrating the use of complementary techniques of functional magnetic
      neuroimaging and neurocognitive studies to identify abnormalities in neural
      circuitry function. RESULTS: Studies of bipolar youths indicate impairment in
      cognitive and affective neural systems and in the interface of these two
      circuits. This evolving field paves a future pathway for identifying diagnostic
      biomarkers for the disorder, providing tools for monitoring response to
      pharmacotherapy, examining illness-associated alterations in developmental
      trajectory, and facilitating the use of animal research for guiding the
      development of novel treatment strategies. CONCLUSIONS: Studies of brain function
      in child psychiatry are establishing a platform of knowledge and methods that
      offer promise for revolutionizing both models of illness pathophysiology and
      future diagnostic and therapeutic practice.

PMID- 18827721
TI  - Neuroanatomical abnormalities in adolescents with attention-deficit/hyperactivity
      disorder.
AB  - OBJECTIVE: Several neuroanatomic abnormalities have been reported in patients
      with attention-deficit/hyperactivity disorder (ADHD). However, findings are not
      always consistent, perhaps because of heterogeneous subject samples. Studying
      youths with documented familial ADHD provides an opportunity to examine a more
      homogeneous population. METHOD: Twenty-four youths with a confirmed history of
      familial ADHD and 10 control youths underwent high-resolution structural magnetic
      resonance imaging examinations. Archived magnetic resonance imaging scan data
      from 12 control youths were included in the analysis to increase statistical
      power. Individually drawn region-of-interest methods were used to examine the
      frontal lobe gyri and caudate. RESULTS: Cerebral total tissue was similar between
      groups. The volumes of the right caudate and right inferior frontal lobe were
      larger in the ADHD youths compared with the control youths. Data from a subgroup
      of the ADHD youths suggest that increasing left caudate volume is associated with
      decreasing functional activation of this region. CONCLUSIONS: Because previous
      studies have focused primarily on younger subjects or used an extended age range,
      the present results may reflect neurodevelopmental changes specific to late
      adolescence in familial ADHD.

PMID- 18827722
TI  - Use of event-related potentials in the study of typical and atypical development.
AB  - A variety of neuroimaging tools are now available for use in studying
      neurodevelopment. In this article, we focus our attention on one such tool--the
      event-related potential (ERP). We begin by providing an overview of what ERPs
      are, their physiological basis, how they are recorded, and some constraints on
      their use. We then provide an abbreviated glossary of ERP components, that is,
      what processes are reflected in ERPs. We conclude by summarizing two areas of
      atypical development that have benefited from this method: children experiencing
      early psychosocial neglect, and children diagnosed with autism. We conclude by
      offering recommendations for future research.

PMID- 18827723
TI  - Regional gray matter volume deficits in adolescents with first-episode psychosis.
AB  - OBJECTIVE: The current study combined baseline voxel-based morphometry and 1-year
      clinical follow-up assessments to examine whether and where regional gray matter
      (GM) volumes differed between a control group and diagnostic subgroups of early
      onset first-episode psychosis (FEP). METHOD: Magnetic resonance imaging brain
      scans were obtained from 70 patients with early-onset FEP, and 51 non-FEP
      controls. Early-onset FEP was defined as age younger than 18 years and a duration
      of positive symptoms of less than 6 months. The age range of the sample was 7 to
      18 years. After a 1-year follow-up, patients were stratified into three
      subgroups: schizophrenia (n = 25), bipolar I disorder (n = 20), and other
      psychoses (n = 25). Regional GM volumes of each patient subgroup were compared
      with those of the control group. RESULTS: A follow-up diagnosis of schizophrenia
      was associated with GM volume deficits in the left medial and left middle frontal
      gyrus; bipolar I disorder was related to a GM volume deficit in the left medial
      frontal gyrus; and not having a follow-up diagnosis of schizophrenia or bipolar
      disorder was associated with smaller bilateral GM volumes in the insula and right
      middle occipital gyrus. CONCLUSIONS: Left medial frontal GM volume deficits were
      common in the groups with schizophrenia and bipolar I disorder, which may point
      to shared underlying pathological findings.

PMID- 18827725
TI  - Cerebral dysfunctions of emotion-cognition interactions in adolescent-onset
      schizophrenia.
AB  - OBJECTIVE: Schizophrenia is among the most severe of psychiatric disorders,
      leading to impairments of affective and cognitive abilities. These dysfunctions
      affect each other mutually. Adolescent-onset schizophrenia (AOS) constitutes a
      particularly severe form of the disorder. In this study, possible dysfunctions of
      the neural correlates underlying the interaction of negative emotion and working
      memory in AOS were investigated. METHOD: During functional magnetic resonance
      imaging, 12 patients with AOS and 12 non-AOS adolescents performed a verbal n
      back task. Intermittently, negative and neutral emotions were induced by
      olfactory stimulation. Group differences in working memory, emotion, and their
      interaction were evaluated. RESULTS: In patients with AOS, lower performance
      sensitivity was observed, along with dorsolateral prefrontal, anterior cingulate,
      and inferior parietal hypoactivation during working memory demands. For negative
      versus neutral emotion induction, patients with AOS mainly showed increased brain
      activation compared with control subjects in widespread brain regions including
      the left orbitofrontal cortex and the medial frontal gyrus. Finally, during the
      interaction of emotion and cognition, altered patterns of activation in patients
      with AOS were found in the thalamocortical network, including the angular and the
      middle cingulate gyri extending to the precuneus. These activation differences
      were further decomposed by parameter estimates. CONCLUSIONS: Our results provide
      new insights into the neural correlates underlying the mutual influence of
      affective and cognitive symptoms in AOS. During the n-back task, areas typically
      associated with working memory performance were found hypoactivated in patients
      relative to the control subjects, including the dorsolateral prefrontal and
      parietal cortex and the anterior cingulate. However, patients with AOS mainly
      demonstrated increased activation in key areas of emotion processing, such as the
      left orbitofrontal cortex and medial frontal areas, during negative emotion
      induction. A dysfunctional thalamocortical network during the interaction mainly
      included regions involved in the integration of converging information--either on
      the subcortical (thalamus) or on a higher-order cortical level (comprising the
      angular gyrus). These findings point to dysfunctional emotion-cognition
      interactions in AOS, which may explain its poor prognosis.

PMID- 18827724
TI  - Toward DSM-V: an item response theory analysis of the diagnostic process for DSM
      IV alcohol abuse and dependence in adolescents.
AB  - OBJECTIVE: Item response theory analyses were used to examine alcohol abuse and
      dependence symptoms and diagnoses in adolescents. Previous research suggests that
      the DSM-IV alcohol use disorder (AUD) symptoms in adolescents may be
      characterized by a single dimension. The present study extends prior research
      with a larger and more comprehensive sample and an examination of an alternative
      diagnostic algorithm for AUDs. METHOD: Approximately 5,587 adolescents between
      the ages of 12 and 18 years from adjudicated, clinical, and community samples
      were administered structured clinical interviews. Analyses were conducted to
      examine the severity of alcohol abuse and dependence symptoms and the severity of
      alcohol use problems (AUDs) within the diagnostic categories created by the DSM
      IV. RESULTS: Although the DSM-IV diagnostic categories differ in severity of
      AUDs, there is substantial overlap and inconsistency in AUD severity of persons
      across these categories. Item Response Theory-based AUD severity estimates
      suggest that many persons diagnosed with abuse have AUD severity greater than
      persons with dependence. Similarly, many persons who endorse some symptoms but do
      not qualify for a diagnosis (i.e., diagnostic orphans) have more severe AUDs than
      persons with an abuse diagnosis. Additionally, two dependence items, "tolerance"
      and "larger/longer," show differences in severity between samples. CONCLUSIONS:
      The distinction between DSM-IV abuse and dependence based on severity can be
      improved using an alternative diagnostic algorithm that considers all of the
      alcohol abuse and dependence symptoms conjointly.

PMID- 18827730
TI  - Diagnostic and therapeutic challenges.

PMID- 18827731
TI  - A classification system for polypoidal choroidal vasculopathy.
AB  - PURPOSE: To describe the demographic features and clinical characteristics of
      polypoidal choroidal vasculopathy (PCV) in Chinese patients and define a new
      classification system. METHODS: Retrospective review of 138 eyes of 123 patients
      presenting to the Singapore National Eye Center with PCV. Patients underwent
      ophthalmologic examination including digital color fundus photography and
      stereoscopic indocyanine green angiography. Classification based on indocyanine
      green angiography findings. RESULTS: Mean age of patient 68.3 years and 62.4%
      were men. PCV was unilateral in 87.8% cases and age-related maculopathy was
      present in the unaffected fellow eye in 22.8%. Average largest size of polyp was
      207 microm. PCV lesions were found in multiple discrete areas in 34.8%. Formation
      of lesion was cluster in 66.7%, single in 27.5%, and string in 5.8%. PCV lesions
      were found in the extrafoveal area in 63.0%, subfoveal in 29.7%, juxtafoveal in
      15.9%, and peripapillary in 8.0%. CONCLUSIONS: Demographics of PCV, unilaterality
      and frequency of age-related maculopathy in fellow eye similar to other reports
      in Asians. We describe a classification system for PCV comprising polyp size,
      location, formation, and number of discrete polyp areas, which can be used for
      prospective interventional clinical studies and may aid in future prognosis and
      management of this condition.

PMID- 18827732
TI  - Evaluation of the safety and performance of an applicator for a novel
      intravitreal dexamethasone drug delivery system for the treatment of macular
      edema.
AB  - PURPOSE: Evaluation of safety and performance of an applicator-inserted
      dexamethasone drug delivery system. METHODS: Patients with clinically observable
      macular edema were randomized to receive 700 microg dexamethasone drug delivery
      system via a pars plana incisional placement (n = 10) or a 22-gauge applicator
      insertion (n = 20). Outcome measures included assessment of procedure duration,
      the postinsertion wound, adverse events, intraocular pressure, and best-corrected
      visual acuity at baseline and days 1, 7, 14, 30, 60, 90, and 180. RESULTS: Both
      procedures were well tolerated and none of the patients in the applicator group
      required sutures to close the insertion wound. The overall incidence of ocular
      adverse events was less in the applicator group (13/19; 68.4%) than the
      incisional group (9/10; 90%), although the difference was not statistically
      significant in this pilot study. Vitreous hemorrhage occurred in two patients in
      the incisional group and none in the applicator group. Increases in intraocular
      pressure were less frequent in the applicator group (3/19; 15.8%) than the
      incisional group (3/10; 30%). No cases of endophthalmitis or retinal detachment
      occurred in either group. The percentage of patients achieving improvement in
      visual acuity of >/=15-letters at Day 90 was similar in both groups; 40% (8/20)
      in the applicator group and 30% (3/10) in the incisional group. CONCLUSION: The
      dexamethasone drug delivery system applicator system performed well, allowing
      safe, effective, and sutureless intravitreal placement of 700 microg
      dexamethasone drug delivery system.

PMID- 18827733
TI  - Clinical evaluation of the safety and efficacy of preservative-free triamcinolone
      (triesence [triamcinolone acetonide injectable suspension] 40 mg/ml) for
      visualization during pars plana vitrectomy.
AB  - PURPOSE: To evaluate the safety and efficacy of preservative-free triamcinolone
      (TRIESENCE(R) suspension) for visualization during pars plana vitrectomy.
      METHODS: This phase III, observer-masked study was conducted in 6 centers by 10
      surgeons and enrolled 60 patients undergoing pars plana vitrectomy. Preservative
      free triamcinolone (up to 4 mg) was administered to all patients to enhance
      visualization of vitreous and membranes. During each surgery, video recordings
      captured visualization pre- and postinstillation of preservative-free
      triamcinolone. An independent, masked reader evaluated the videos for the degree
      of visualization using a five-point scale ranging from 0 (not visible) to 4
      (clearly delineated). Surgeons used a five-point scale ranging from "strongly
      disagree" to "strongly agree" to assess whether preservative-free triamcinolone
      improved visualization. RESULTS: In 59 of 60 cases, the masked reader's scores
      for visualization of posterior segment structures were higher (i.e., structures
      were more clearly visible) after instillation of preservative-free triamcinolone.
      The preinstillation mean visualization score was 0.5 compared to 3.7
      postinstillation (P < 0.0001). Greater than 90% of surgeon evaluations agreed or
      strongly agreed that preservative-free triamcinolone enhanced visualization of
      posterior segment structures. No safety issues were identified. CONCLUSIONS:
      Preservative-free triamcinolone (TRIESENCE(R) suspension) was well tolerated and
      effectively enhanced visualization of posterior segment structures during pars
      plana vitrectomy.

PMID- 18827734
TI  - Outcomes of sulfur hexafluoride (SF6) versus perfluoropropane (C3F8) gas
      tamponade for macular hole surgery.
AB  - PURPOSE: To compare outcomes of macular hole surgery using sulfur hexafluoride
      (SF6) gas versus perfluoropropane (C3F8) gas for idiopathic macular hole repair.
      DESIGN: Retrospective, interventional, comparative cohort study. METHODS:
      Institutional clinical practice. A consecutive group of patients undergoing
      macular hole surgery with SF6 group (38 eyes of 38 patients) and a
      nonconsecutive, contemporaneous, comparison group with C3F8 was used (41 eyes of
      39 patients). Vitrectomy for macular hole surgery using either of two different
      gases for internal tamponade. Best corrected logarithm of minimal angle
      resolution visual acuity, anatomic closure, reoperations, development of
      cataract, and complications such as retinal detachment. RESULT: The macular hole
      closure rate was similar in both groups [34/38 (90%) with SF6 gas versus 37/41
      (91%) with C3F8 gas, P = 0.91]. At 6 months after macular hole surgery, best
      corrected visual acuity was improved compare with baseline visual acuity by a
      mean of 0.32 logarithm of minimal angle resolution in the SF6 group (P = 0.045)
      and 0.52 logarithm of minimal angle resolution in the C3F8 group (P < 0.001).
      Development of vision-impairing cataract in phakic eyes was not different, but
      the myopic shift was greater in the C3F8 group (P = 0.016). CONCLUSION: Macular
      hole surgery using SF6 gas yields similar results as with C3F8 gas and may be a
      good option.

PMID- 18827735
TI  - Primary intravitreal bevacizumab for subfoveal choroidal neovascularization in
      age-related macular degeneration: results of the Pan-American Collaborative
      Retina Study Group at 12 months follow-up.
AB  - PURPOSE: To report the 12-month anatomic and Early Treatment Diabetic Retinopathy
      Study best-corrected visual acuity (BCVA) response after primary intravitreal
      bevacizumab (Avastin, Genentech Inc., San Francisco, CA) (1.25 mg or 2.5 mg) in
      patients with subfoveal choroidal neovascularization secondary to age-related
      macular degeneration. METHODS: Sixty-three eyes of 63 consecutive patients with
      subfoveal choroidal neovascularization secondary to age-related macular
      degeneration, a mean age of 73.7 +/- 7.5 years and a minimum of 12 months (mean
      55.5 +/- 6.2 weeks) of follow-up participated in this interventional
      retrospective multicenter case series in 7 centers from 6 countries. Patients
      were treated with at least 1 intravitreal injection of 1.25 mg or 2.5 mg of
      bevacizumab. Patients underwent Early Treatment Diabetic Retinopathy Study BCVA
      testing, ophthalmoscopic examination, optical coherence tomography, and
      fluorescein angiography at baseline and follow-up visits. Repeated measures
      analysis of variance was used to compare mean values. RESULTS: The mean number of
      intravitreal bevacizumab injections per eye was 3.5 (range, 1-8). Mean baseline
      BCVA was 20/320, logarithm of the minimum angle of resolution = 1.2, and mean
      final BCVA was 20/200, logarithm of the minimum angle of resolution = 1.0 (P <
      0.001). Central macular thickness at baseline by optical coherence tomography had
      a mean of 389.2 +/- 149.6 microm which was significantly reduced to a mean of
      281.0 +/- 96.1 microm, 268.2 +/- 82.6 microm, 262.6 +/- 92.3 microm, and 241.3 +/
      76.7 microm at 1, 3, 6, and 12 months after initial treatment, respectively (P <
      0.0001). Ocular adverse events included transient increased intraocular pressure
      in 2 (3.1%) eyes, endophthalmitis in 2 (3.1%) eyes, and transient hypotony in 1
      eye (1.1%). No systemic adverse events were observed. CONCLUSION: Primary
      intravitreal bevacizumab at doses of 1.25 mg or 2.5 mg seems to provide stability
      or improvement in BCVA, optical coherence tomography, and fluorescein angiography
      in subfoveal choroidal neovascularization secondary to age-related macular
      degeneration at 12 months.

PMID- 18827736
TI  - Analysis of the neuronal marker protein gene product 9.5 in internal limiting
      membranes after indocyanine-green assisted peeling.
AB  - BACKGROUND: Indocyanine green-assisted internal limiting membrane (ILM) peeling
      was suspected to disrupt the innermost layer of the neural retina. We examined
      whether surgically excised specimens contain remnants of neuronal tissue.
      METHODS: Ten patients with macular hole underwent pars plana vitrectomy and
      indocyanine green-assisted ILM peeling. A total of 0.1 mL of a 0.5% indocyanine
      green solution was applied for 15 seconds. The ILM specimens were prepared for
      immunohistochemistry, using a polyclonal antibody against protein gene product
      9.5. Protein gene product 9.5 is a pan-neuronal marker labeling human neuronal
      cells. Appropriate controls to show selectivity of the antibody were performed on
      neuronal tissue of donor eyes. One ILM was prepared for electron microscopy.
      RESULTS: A selective expression of protein gene product 9.5 was found in neuronal
      fibers of the retina and optic nerve of donor eyes. Only 1 of the 10 surgical ILM
      specimens showed a minimal focal positivity for protein gene product 9.5. No
      neuronal tissue was detected on the ILM by electron microscopy. CONCLUSION: Focal
      expression of protein gene product 9.5 in only 1 of 10 surgical ILM specimens
      argues against a general indocyanine green-related disruption of the innermost
      retinal layers. However, higher concentrations of the dye, longer incubation
      times or different solvents than used in this study may lead to different
      results.

PMID- 18827737
TI  - Incidence of endophthalmitis related to intravitreal injection of bevacizumab and
      ranibizumab.
AB  - PURPOSE: To report the overall incidence of endophthalmitis associated with
      office based intravitreal injections of bevacizumab and ranibizumab. METHODS:
      This is a retrospective, consecutive, multicenter case series involving four
      large clinical sites. Included were all patients receiving at least one injection
      of intravitreal bevacizumab or intravitreal ranibizumab. Follow-up after each
      injection was at least 4 weeks. RESULTS: A total of 12,585 injections of
      intravitreal bevacizumab and 14,320 injections of intravitreal ranibizumab were
      given during the study period. Infectious endophthalmitis developed in three
      patients after administration of bevacizumab and in three patients after
      administration of ranibizumab. Four of these patients were culture positive.
      Rates of endophthalmitis were 0.02% and 0.02%, respectively, with an overall rate
      of 0.02%. CONCLUSION: The rate of endophthalmitis associated with intravitreal
      bevacizumab and ranibizumab is low, with an incidence of approximately 1 in 4,500
      injections.

PMID- 18827738
TI  - Improved visualization of polypoidal choroidal vasculopathy lesions using
      spectral-domain optical coherence tomography.
AB  - PURPOSE: To report the tomographic features of vascular lesions beneath the
      retinal pigment epithelium in eyes with polypoidal choroidal vasculopathy by
      using spectral-domain optical coherence tomography (SD-OCT). DESIGN:
      Retrospective observational case series. METHODS: Angiograms and images obtained
      using the prototype SD-OCT system were compared for 21 eyes of 21 patients with
      polypoidal choroidal vasculopathy to identify sub-retinal pigment epithelium
      abnormalities visible on three-dimensional and enhanced SD-OCT images. RESULTS:
      On angiography, a branching vascular network and at least 1 polypoidal lesion
      were visible in all 21 eyes; 10 eyes also had pigment epithelial detachment
      (PED). SD-OCT revealed a thin straight line of high reflectivity-Bruch's membrane
      associated with the branching vascular network in all 21 eyes, polypoidal
      lesions, 19 (90%) of the 21 eyes; and PED, 9 (90%) of the 10 eyes with PED. The
      vascular abnormalities of polypoidal choroidal vasculopathy (polypoidal lesion
      and branching vascular network) identified with angiograms were visualized on SD
      OCT images in 20 of the 21 eyes (95%) as areas of moderate reflectivity between
      the clearly delineated abnormal section of retinal pigment epithelium and Bruch's
      membrane. CONCLUSIONS: Enhanced SD-OCT imaging clearly depicted Bruch's membrane
      beneath areas of abnormal retinal pigment epithelium in the same locations where
      the vascular abnormalities of polypoidal choroidal vasculopathy were evident on
      angiography.

PMID- 18827739
TI  - Expression of cyclooxygenase-2 in choroidal neovascular membranes from age
      related macular degeneration patients.
AB  - PURPOSE: The objective of this study was to investigate the expression of
      cyclooxygenase (COX)-2 in human choroidal neovascular membranes. METHODS:
      Paraffin-embedded sections of choroidal neovascular membranes excised from 16
      patients with wet age-related macular degeneration were used for this study.
      Sections were subjected to immunohistochemistry using a monoclonal mouse
      antihuman COX-2 antibody. Staining was classified as either negative or positive
      in retinal pigment epithelial cells, vascular endothelial cells, and fibroblasts.
      Serial sections were stained for vimentin expression to confirm tissue
      antigenicity. RESULTS: Eleven of 16 (69%) choroidal neovascular membranes stained
      positive for COX-2 in retinal pigment epithelial cells, with 6 (38%) of these
      also expressing COX-2 in vascular endothelial cells and 6 (38%) in fibroblasts.
      None of the sections that were negative for COX-2 in the retinal pigment
      epithelial cells showed COX-2 expression in the other cell types assessed. There
      was a statistically significant difference (P = 0.0097) in the mean ages between
      the COX-2 positive group (65.6 years) and COX-2 negative group (76.8 years) as
      determined by a two-tailed, unpaired Student's t-test. CONCLUSION: The expression
      of COX-2 in human choroidal neovascular membranes suggests a possible role for
      this modulator in age-related macular degeneration pathogenesis. The age
      dependent expression observed is novel and warrants further investigation.

PMID- 18827740
TI  - Central and pericentral retinal sensitivity after macular translocation surgery.
AB  - PURPOSE: To evaluate the separate contribution of the retina versus retinal
      pigment epithelium (RPE)-choriocapillaris to visual function after treatment of
      neovascular age-related macular degeneration by measuring retinal sensitivity
      across three areas after macular translocation surgery. METHODS: Using the Nidek
      microperimeter-1, we tested retinal sensitivity across three areas in 35 patients
      after macular translocation surgery. Microperimetry scores ranged from -2 (no
      response to brightest stimulus) to 20 (response with 20 dB neutral density
      filtering). Median retinal sensitivity score (MRSS) for the central 10-degrees
      (Area 1, fovea translocated over healthier RPE) was compared with acuity, reading
      speed and MRSS of adjacent areas: Area 2, retina over site of choroidal
      neovascularization removal and Area 3, retina over undisturbed RPE. RESULTS: In
      27 of 35 eyes in this study (77%), the MRSS for Area 1, was greater than Area 2.
      Area 1 was a median of 3.0 decibels (dB) greater in sensitivity (range, 16
      greater-2 lower) than Area 2 (P < or = 0.001), and 5.0 dB lower (range, 2 greater
      12 lower) than Area 3 (P < or = 0.001). The median of the MRSS (25th/75th
      percentile) for Areas 1, 2 and 3 were 2.0 (0.0/6.0), -2.0 (-2.0/-2.0) and 9
      (4.0/12.0), respectively. The MRSS for Area 1 correlated with reading speed more
      than with acuity. CONCLUSIONS: Sensitivity of the translocated macula was
      significantly greater than in Area 2, retina over abnormal RPE-choriocapillaris,
      suggesting that disturbed RPE-choriocapillaris significantly limits retinal
      function. Area 1 sensitivity was lower than in retina unaffected by age-related
      macular degeneration over undisturbed RPE, suggesting that persisting retinal
      dysfunction can limit vision recovery.

PMID- 18827741
TI  - Losartan prevents sepsis-induced acute lung injury and decreases activation of
      nuclear factor kappaB and mitogen-activated protein kinases.
AB  - Lack of specific and efficient therapy leads to the high mortality rate of acute
      lung injury (ALI) and acute respiratory distress syndrome (ARDS). Losartan is a
      potent pharmaceutical drug for ALI/ARDS. However, the protective effects and
      mechanisms of losartan remain incompletely known. This study evaluates the
      effects of losartan on ALI/ARDS and further investigates the possible mechanisms
      of these protective effects. Mice received i.p. injections of the AT1 inhibitor
      losartan (15 mg/kg), or control vehicle, half hour after cecal ligation and
      puncture (CLP). Plasma TNF-alpha, IL-1beta, and IL-6 cytokines were assayed 6 h
      after CLP. Blood gas, wet/dry lung weight ratio, lung tissue histology for
      occurrence of ALI/ARDS, and survival were examined. Lastly, nuclear factor kappaB
      (NF-kappaB) activations, IkappaB-alpha degradations, phosphorylations of p38
      MAPK, extracellular signal-regulated kinase 1/2, and c-Jun N-terminal kinase
      expressions were evaluated in lung tissue. Losartan treatment significantly
      attenuated TNF-alpha, IL-6, and IL-1beta 6 h after CLP. Furthermore, losartan
      prevented blood gas and histopathologic appearance of ALI/ARDS after sepsis and
      significantly improved survival. Finally, losartan given after sepsis led to
      inhibition of lung tissue NF-kappaB activation (P < 0.01 vs. CLP group),
      attenuated degradation of IkappaB-alpha, and inhibited phosphorylation of
      p38MAPK, extracellular signal-regulated kinase 1/2, and c-Jun N-terminal kinase,
      pathways critical for cytokine release. These data reveal that losartan exerts a
      protective effect on ALI/ARDS, and this protective effect may be dependent, at
      least in part, on NF-kappaB and MAPK mechanisms.

PMID- 18827742
TI  - Hemoglobin vesicles and red blood cells as carriers of carbon monoxide prior to
      oxygen for resuscitation after hemorrhagic shock in a rat model.
AB  - Hemoglobin vesicles (HbVs) are artificial oxygen (O2) carriers that encapsulate
      concentrated hemoglobin (Hb) solution in phospholipid vesicles (liposomes).
      Recent reports on cytoprotective effects of exogenous carbon monoxide (CO) urged
      us to test infusion of CO-bound HbV (CO-HbV) and red blood cells (CO-RBC) in
      hemorrhagic-shocked rats to improve tissue viability over that of O2-bound HbV
      (O2-HbV) and O2-bound RBC (O2-RBC). Male Wistar rats were anesthetized with 1.5%
      sevoflurane inhalation (FiO2 = 21%) while spontaneous breathing was maintained.
      Shock was induced by 50% blood withdrawal from femoral artery. Fifteen minutes
      later, they received CO-HbV, CO-RBC, O2-HbV, O2-RBC, or empty vesicles (EV)
      suspended in 5% recombinant albumin. All groups showed prompt recovery of blood
      pressure and blood gas parameters just after resuscitation and survived for 6 h
      of observation period. However, only the EV group showed significant hypotension
      at 3 and 6 h. Plasma enzyme levels were elevated at 6 h, especially in the O2
      HbV, O2-RBC, and EV groups. They were significantly lower in the CO-HbV and CO
      RBC groups than in the O2-bound fluids. Immunohistochemical staining of 3
      nitrotyrosine exhibited less oxidative damage in the liver and lung for CO-HbV
      and CO-RBC groups. Blood carbonyl Hb levels (26%-39% immediately after infusion)
      decreased to less than 3% at 6 h while CO was exhaled through the lung. Both HbV
      and RBC gradually gained the O2 transport function. Collectively, both CO-HbV and
      CO-RBC showed a resuscitative effect for hemorrhagic-shocked rats. They reduced
      oxidative damage to organs in comparison to O2-HbV and O2-RBC. Adverse and
      poisonous effects of CO gas were not evident for 6 h in this experimental model.
      Further study is necessary to clarify the neurological impact of a longer
      observation period for eventual clinical applications.

PMID- 18827743
TI  - Local preconditioning by thermal stress accelerates microvascular thrombus
      formation.
AB  - Heme oxygenase 1 (HO-1) has been shown to suppress microvascular thrombus
      formation. Because stress conditioning induces HO-1 and, in addition, the
      anticoagulant thrombomodulin and thrombospondin 1, we studied the effect of
      hyperthermic and hypothermic local stress conditioning on microvascular thrombus
      formation. For local stress conditioning, the hindlimb of Sprague-Dawley rats was
      subjected to local heating (42.5 degrees C) or cooling (4 degrees C) for 30 min
      at 24 h before induction of thrombosis. Sham-exposed hindlimbs served as
      controls. Thrombosis was induced photochemically in arterioles and venules of the
      preconditioned tissue (muscle, subcutis, and periosteum) by continuous light
      exposure after injection of a fluorescent dye. Immunohistochemistry revealed that
      stress conditioning distinctly induced HO-1, thrombomodulin, and thrombospondin 1
      but also von Willebrand factor in endothelial cells. Of interest, intravital
      fluorescence microscopic analysis of the kinetics of thrombus formation could not
      confirm an antithrombotic effect of stress conditioning but showed, in contrast,
      a significant acceleration of thrombosis (P < 0.05) in both arterioles and
      venules of either of the tissues studied. Although hypothermic and hyperthermic
      stress conditioning induces antithrombotic HO-1, thrombomodulin, and
      thrombospondin 1, it enhances endogenous thrombogenicity, most probably due to
      upregulation of the prothrombotic von Willebrand factor. Thus, preconditioning
      with local stress cannot be considered as a strategy to prevent thrombus
      formation.

PMID- 18827744
TI  - Toll-like receptor 4 regulates heme oxygenase-1 expression after hemorrhagic
      shock induced acute lung injury in mice: requirement of p38 mitogen-activated
      protein kinase activation.
AB  - Acute lung injury (ALI) leading to respiratory distress is a common sequela of
      shock or trauma. The toll-like receptors (TLRs) stand at the interface of innate
      immune activation in the settings of both infection and sterile injury by
      responding to a variety of microbial and endogenous ligands alike. This work
      explored the effects of TLR-4 on hemorrhage-induced ALI and characterizes the
      signaling pathways and the mechanisms involved in noninfectious ALI. Mice
      underwent hemorrhagic shock and resuscitation (HSR). Arterial blood gases;
      expressions of TLR-4, heme oxygenase 1 (HO-1), and p38 mitogen-activated protein
      kinase (p38MAPK); myeloperoxidase activity; lung wet/dry ratios; and IL-10 levels
      in lung tissues were obtained at 6, 24, and 48 h after HSR. Hemorrhagic shock and
      resuscitation induced significant expressions of TLR-4, HO-1, and p38MAPK in
      C3H/HeN mice. IL-10 and myeloperoxidase were markedly increased at 24 h after
      HSR, and C3H/HeN mice had ALI with PaO2/fraction of inspired oxygen less than 300
      mmHg. The induced amount of each cytokine level and the expressions of TLR-4, HO
      1, and p38MAPK of C3H/HeN mice were significantly higher compared with C3H/HeJ
      mice. This study demonstrated that lung p38MAPK is activated after HSR, and
      p38MAPK inhibitor FR167653 suppresses HO-1 induction after ALI. We concluded that
      TLR-4 might induce HO-1 messenger RNA expression, which is probably involved in
      p38MAPK activation in the development of the lung dysfunction after HSR.

PMID- 18827745
TI  - Endothelial nitric oxide synthase G894T (GLU298ASP) polymorphism is associated
      with hypotension in patients with E. coli bacteremia but not in bacteremia caused
      by a gram-positive organism.
AB  - Nitric oxide (NO) as a vasoactive substance is a crucial element in the
      pathogenesis of sepsis. Endothelial NO synthase (eNOS) is, in turn, a key
      regulator of vascular NO production. The eNOS gene polymorphism at position 894
      (G>T, Glu298Asp) resulting in T allele has been studied in the context of
      vascular diseases, but its role in sepsis has not yet been explored. We here
      studied the effect of eNOS Glu298Asp polymorphism on the clinical course of the
      disease in patients with bacteremia. The study comprised 147 patients with
      bacteremia caused by Staphylococcus aureus, Streptococcus pneumoniae, beta
      hemolytic streptococci, or Escherichia coli. Laboratory findings and clinical
      data were registered on admission and during 6 consecutive days. The polymorphism
      of eNOS gene, G894T, was genotyped. Carriage of the T allele was associated with
      low MAP (P = 0.004) and high Sequential Organ Failure Assessment score (P =
      0.001) in patients with E. coli bacteremia. The effect on blood pressure was most
      prominent in the early stage of the disease (MAP on admission = 52 mmHg in T
      allele carriers vs. 91 mmHg in noncarriers; P < 0.001). However, the same was not
      detected in bacteremia caused by a gram-positive organism (S. aureus, S.
      pneumoniae, or beta-hemolytic streptococci). The Glu298Asp polymorphism had no
      effect on case fatality in any pathogen. Carriage of the T allele of the eNOS
      gene is a risk factor for hypotension in patients with E. coli bacteremia but not
      in bacteremia caused by a gram-positive organism.

PMID- 18827746
TI  - Release of melanotroph- and corticotroph-type proopiomelanocortin derivatives
      into blood after administration of corticotropin-releasing hormone in patients
      with septic shock without adrenocortical insufficiency.
AB  - The aim of the study was to assess the adequacy of pituitary function by
      determining the plasma concentrations of corticotroph-type (corticotropin, beta
      endorphin immunoreactive material [beta-END IRM], authentic beta-END, and beta
      lipotropin IRM) as well as melanotroph-type (alpha-melanocyte-stimulating hormone
      [alpha-MSH] and N-acetyl-beta-END [Nac-beta-END] IRM) proopiomelanocortin (POMC)
      derivatives in patients under septic shock upon administration of corticotropin
      releasing hormone (CRH). The objectives were to assess whether an insufficient
      release of corticotroph- or melanotroph-type POMC derivatives from the pituitary
      into the cardiovascular compartment correlates with the 28-day mortality rate.
      Seventeen patients with septic shock but without adrenocortical insufficiency and
      16 healthy volunteers were enrolled in the study, and CRH stimulation tests were
      performed with an i.v. bolus injection of 100 microg human CRH. After treatment
      with CRH, plasma concentrations of corticotroph-type POMC derivatives increased
      in survivors and nonsurvivors, melanotroph-type POMC derivatives such as alpha
      MSH or Nac-beta-END IRM increased only in survivors in contrast to nonsurvivors.
      The release of alpha-MSH and Nac-beta-END IRM was suppressed by dexamethasone in
      survivors but not in nonsurvivors. In patients with septic shock, the response of
      the pituitary to CRH stimulation in terms of alpha-MSH or Nac-beta-END IRM
      release was impaired in nonsurvivors compared with survivors or controls. Reduced
      responses of alpha-MSH or Nac-beta-END IRM to CRH and the invalid suppression by
      dexamethasone reflect a state of dysfunction of the melanotroph-type POMC system
      in nonsurvivors. Considering anticytokine and anti-inflammatory effects of alpha
      MSH, this dysfunction may increase the risk of death in patients with septic
      shock.

PMID- 18827747
TI  - Coupled plasma filtration adsorption in experimental peritonitis-induced septic
      shock.
AB  - The coupled plasma filtration adsorption (CPFA) was developed as an adsorptive
      hemopurification method aimed at nonselective removal of circulating soluble
      mediators potentially involved in the pathogenesis of sepsis. We hypothesized
      that this nonselective hemopurification could protect from detrimental
      consequences of long-term, volume-resuscitated porcine septic shock. In 16
      anesthetized, mechanically ventilated, and instrumented pigs, the hyperdynamic
      septic shock secondary to peritonitis was induced by intraperitoneally
      inoculating feces and maintained for 22 h with fluid resuscitation and
      norepinephrine infusion as needed to maintain MAP above 65 mmHg. After 12 h of
      peritonitis, animals were randomized to receive either supportive treatment
      (control, n = 8) or CPFA treatment (CPFA, n = 8). Systemic, hepatosplanchnic, and
      renal hemodynamics; oxygen exchange; energy metabolism (lactate/pyruvate and
      ketone body ratios); ileal mucosal and renal cortex microcirculation; systemic
      inflammation (TNF-alpha, IL-6); nitrosative/oxidative stress (thiobarbituric acid
      reactive species, nitrates + nitrites); and endothelial/coagulation dysfunction
      (asymmetric dimethylarginine, von Willebrand factor, thrombin-antithrombin
      complexes, platelet count) were assessed before and 12, 18, and 22 h of
      peritonitis. Coupled plasma filtration adsorption neither delayed the development
      of hypotension nor reduced the dose of norepinephrine. The treatment failed to
      attenuate sepsis-induced alterations in microcirculation, surrogate markers of
      cellular energetics, endothelial injury, and systemic inflammation. Similarly,
      CPFA did not protect from lung and liver dysfunction and even aggravated sepsis
      induced disturbances in coagulation and oxidative/nitrosative stress. In this
      porcine model of septic shock, the early treatment with CPFA was not capable of
      reversing the sepsis-induced disturbances in various biological pathways and
      organ systems. Both the efficacy and safety of this method require further
      rigorous experimental validation in clinically relevant models.

PMID- 18827748
TI  - Deferoxamine mimics the pattern of hypoxia-related injury at the
      microvasculature.
AB  - Oxygen is essential for the maintenance of life, and when oxygen levels decline
      to critical levels, a program of complex mechanisms exists to i) sense hypoxia,
      ii) respond to minimize acute tissue injury, and iii) result in adaptations that
      offer protection against further hypoxia challenges. Alternative adaptation
      related protection may also be inducible through the increased activity of
      hypoxia-inducible factors activated by hypoxia mimics such as iron chelation with
      deferoxamine (DFA). We have characterized a set of hypoxia-related responses at
      the microvasculature and postulated that microvascular injury in response to
      hypoxia could be reproduced by the reduction of bioavailable iron through
      chelation by DFA. We were able to induce a similar degree of leukocyte adherence
      and emigration and vascular leak with DFA infusion as compared with hypoxia
      exposure in an intact physiological rodent model. However, in contrast to hypoxia
      exposed groups, we were unable to detect reactive oxygen species or alter the
      injury pattern with reactive oxygen species scavenger in the groups treated with
      DFA. Thus, we demonstrate that DFA mimics the pattern and intensity of hypoxia
      related injury on the microvasculature; however, differences in the time course
      and mechanism of injury were identified. In addition, DFA saturated with iron did
      not completely reverse the effects of DFA, suggesting a mechanism(s) beyond a
      reduction in the bioavailability of iron. These findings may have importance in
      the targeting of iron for the development of hypoxia mimics that may offer
      protection against subsequent hypoxia exposure in clinical setting such as
      myocardial infarction and stroke.

PMID- 18827749
TI  - Low-dose dexamethasone-supplemented fluid resuscitation reverses endotoxin
      induced acute renal failure and prevents cortical microvascular hypoxia.
AB  - There is growing evidence that impairment in intrarenal oxygenation and hypoxic
      injury might contribute to the pathogenesis of septic renal failure. An important
      molecule known to act on the renal microvascular tone and therefore consequently
      being involved in the regulation of intrarenal oxygen supply is NO. The main
      production of NO under septic conditions derives from iNOS, an enzyme that can be
      blocked by dexamethasone (DEX). In an animal model of endotoxin-induced renal
      failure, we tested the hypothesis that inhibition of iNOS by low-dose DEX would
      improve an impaired intrarenal oxygenation and kidney function. Twenty-two male
      Wistar rats received a 30-min intravenous infusion of LPS (2.5 mg/kg) and
      consecutively developed endotoxemic shock. Two hours later, in 12 animals, fluid
      resuscitation was initiated. Six rats did not receive resuscitation; four animals
      served as time control. In addition to the fluid, six animals received a bolus of
      low-dose DEX (0.1 mg/kg). In these animals, the renal iNOS mRNA expression was
      significantly suppressed 3 h later. Dexamethasone prevented the appearance of
      cortical microcirculatory hypoxic areas, improved renal oxygen delivery, and
      significantly restored oxygen consumption. Besides a significant increase in MAP
      and renal blood flow, DEX restored kidney function and tubular sodium
      reabsorption to baseline values. In conclusion, treatment with low-dose DEX in
      addition to fluid resuscitation reversed endotoxin-induced renal failure
      associated by an improvement in intrarenal microvascular oxygenation. Therefore,
      low-dose DEX might have potential application in the prevention of septic acute
      renal failure.

PMID- 18827750
TI  - Characterization of S. pneumoniae pneumonia-induced multiple organ dysfunction
      syndrome: an experimental mouse model of gram-positive sepsis.
AB  - Streptococcus pneumoniae, a gram-positive bacteria, is the most common cause of
      community-acquired pneumonia. It is a common cause of septic shock with multiple
      organ dysfunction syndrome (MODS) resulting in significant mortality. Gram
      positive mouse models of sepsis with MODS are required to examine mechanisms of
      immune responses in severe sepsis. To assess whether lung infection due to S.
      pneumoniae in a nonventilated mouse model can induce multiple organ dysfunction.
      S. pneumoniae, SPN 15814 strain, harvested at log phase, was injected
      intratracheally in C57BL/6 mice at OD 600 between 0.35 and 0.63. A dose of
      bacteria at OD 600 = 0.63 conferred approximately 30% mortality in 36 h. Lung
      pneumonia was assessed by histology, lung myeloperoxidase activity, and lung
      bacterial load; intestinal epithelial barrier integrity was assessed by measuring
      blood-to-lumen clearance of Cr-EDTA; renal function was assessed by measuring
      plasma creatinine and urea; and myocardiac function was assessed using an
      isolated perfused mouse heart model. S. pneumoniae-induced pneumonia resulted in
      neutrophil infiltration into the lungs and increased lung bacterial load.
      Although relatively few bacteria gained access to the blood stream, the pneumonia
      was accompanied by increased intestinal epithelial barrier permeability,
      increased plasma creatinine, and decreased cardiac output and stroke volume.
      These data clearly show that intratracheal S. pneumoniae induced not only
      pneumonia but also MODS, despite the fact that few organisms gain access to the
      blood stream. This model can be used as a good gram-positive model of sepsis and
      MODS for further studies.

PMID- 18827751
TI  - Suicide risk: where, why and how is it generated?
AB  - In this editorial we will first use the findings of epidemiological research to
      show that the closer we get to brain dysfunction, the higher is the suicide risk
      (Where?). Secondly, a distinction will be made between the proximate and ultimate
      causation of suicide behaviour as a biological phenomenon (Why?). Using the
      evolutionary psychiatry approach, the ultimate causation of suicide could answer
      the question why does suicidal behaviour exist at all? Third, we will review the
      most attractive recent molecular genetic findings in the field of suicidology
      genetics (How?). These three perspectives will in turn lead us to summarise
      where, why and how suicide risk is generated?

PMID- 18827752
TI  - NA+, K+-ATPase activity in the brain of the rats with kainic acid-induced
      seizures: influence of lamotrigine.
AB  - OBJECTIVE: Kainic acid (KA) is used as an experimental agent which produces
      convulsions and neurotoxic lesions. Lamotrigine (LTG) is an antiepileptic drug, a
      glutamate release inhibitor, with action at the neuronal voltage-gated sodium
      channel. The aim of the present study was to investigate the Na+-K+-ATPase
      activity in the hippocampus and cortex of rats with KA-induced convulsions.
      Further, this study was also designed to investigate the influence of the LTG pre
      treatment on the mentioned hippocampal and cortex changes. MATERIALS AND METHODS:
      The study was carried out on Hannover-Wistar rats. Na+, K+-ATPase activity from
      hippocampal and temporal cortex tissue was determined two hours after a single
      subcutaneous KA (8 mg/kg) injection as well as on the third or the fifth
      experimental day. LTG (30 mg/kg i.p.) was used one hour before KA application and
      during the next two or four consecutive days. All animals of KA and KA+LTG groups
      were observed during the first 2 hours after KA application and their behavior
      was noted. Only animals with characteristically KA-induced behavioral changes
      observed were used in the study. KA typical behavioral changes were confirmed
      with electroencephalography. RESULTS: After KA application, Na+, K+-ATPase
      activity was significantly inhibited. Na+-K+-ATPase activity inhibition in the
      hippocampus of the LTG pretreated rats on the fifth experimental day was
      statistically less pronounced than in KA treated rats. The LTG pretreatment
      showed also a protective effect on the Na+-K+-ATPase activity in the rats' brain
      cortex. CONCLUSION: KA systemic application induced Na+, K+- ATPase activity
      inhibition in the rat hippocampus and cortex and LTG pre-treatment showed a
      partially protective effect on the enzyme activity.

PMID- 18827753
TI  - Post traumatic stress disorder, depression and anxiety among family medicine
      residents after 1992-95 war in Bosnia and Herzegovina.
AB  - BACKGROUND: The traumatic events experienced in Bosnia and Herzegovina during the
      1992-1995 conflict may have a lasting effect on the mental health of the
      citizens, characterized by high rates of post-traumatic stress disorder (PTSD),
      depression, and anxiety. A diagnosis of PTSD, depression, and anxiety among
      family physician residents could affect their ability to diagnose and treat
      patients for depression, anxiety and PTSD. OBJECTIVES: To assess PTSD, depression
      and anxiety symptoms and prevalence amongst family medicine residents (FMR) who
      were general practitioners (GP) in different war engagements and compare them
      with FMR who were medical students, 9 years after the 1992-1995 war in Bosnia
      Herzegovina (BH). SUBJECTS AND METHODS: We applied the Bosnia-Herzegovina
      versions of both the Harvard Trauma Questionnaire (HTQ) for PTSD symptoms, and
      Hopkins Symptom Checklist - 25 (HSCL-25) for anxiety and depression symptoms to
      78 residents (age 30-45 years, 84.6% females), who lived in BH during the
      conflict years. RESULTS: PTSD prevalence of 10.3% and depression and anxiety
      prevalence of 21.8%, was found. The anxiety symptoms score was significantly
      higher amongst FMR who were GPs (1.69+/-0.66) than medical students (1.40+/-0.41,
      t-test=2.219, P=0.029) during the war.

PMID- 18827754
TI  - Reliability and validity of DSM-IV Axis V scales in a clinical sample of veterans
      with posttraumatic stress disorder.
AB  - OBJECTIVES: Psychometric properties of the DSM-IV Axis V scales in measuring
      adaptational functioning of psychotraumatised veterans have been chosen as the
      focus of this study. SUBJECTS AND METHODS: The reliability and validity of the
      Global Assessment of Functioning Scale (GAF), the Social and Occupational
      Assessment Scale (SOFAS), and the Global Assessment of Relational Functioning
      (GARF) were examined in a clinical sample of 129 veterans with posttraumatic
      stress disorder (PTSD). RESULTS: The interrater reliability of the GAF (ICC=0.82)
      and the SOFAS (ICC=0.83) was excellent, while the interrater reliability of the
      GARF (ICC=0.75) was good. Correlations with other clinician-rated scales of
      psychopathology and overall functioning showed that the GAF is primarily related
      to a reduction in functioning due to psychiatric symptoms, while an assessment of
      functioning beyond psychopathology, considering the effects of the individual's
      general medical condition as well, was provided by the SOFAS and the GARF, which
      is of importance for a comprehensive evaluation of the patients' health status.
      The factor analysis of the Axis V scales revealed a theoretically meaningful,
      single common factor (variance accounted for by the extracted factor = 76.91%),
      while observed differences, between the subjects with complete and partial PTSD,
      in scores on the axis V scales support further use of the axis V scales as useful
      outcome variables. CONCLUSION: The issue of a valid and reliable measurement of
      functional impairment is of paramount importance not only in the domain of
      clinical psychiatry but in forensic practice as well. In this respect, our
      findings give strong support to extending the scope of the DSM axis V scales with
      the two experimental scales which provide both conceptual framework and useful
      tools for reliable and valid evaluation of adaptatinal functioning in persons
      suffering from PTSD.

PMID- 18827755
TI  - Patterns of psychiatric consultation in an Austrian tertiary care center -
      results of a systematic analysis of 3,307 referrals over 2 years.
AB  - OBJECTIVE: The purpose of this study was to investigate the phenomenology of a
      newly structured Austrian tertiary - care hospital consultation - liaison (C - L)
      psychiatry service. SUBJECTS AND METHODS: We compared two 1 - year surveys over
      two years of observation (2003 - 2005). Survey A (August 1, 2003, until July 31,
      2004) comprised 1474 consecutive new consultations, and the more recent Survey B
      (August 1, 2004, until July 31, 2005) extended over 1833 consecutive new
      referrals to our C - L service. Psychiatric referrals were analyzed with regard
      to consultation rate, demographic characteristics, referring departments,
      principal reasons for referral, diagnostic characteristics, and intervention
      patterns. RESULTS: The consultation rate increased by 0.61% from 2.69% in Survey
      A to 3.30% in Survey B. Internal medicine consistently accounted for almost 31%
      of all referrals in both surveys. In Survey A, the most common psychiatric
      diagnoses were adjustment disorders (21.4%), depressive disorders (18.5%), and
      delirium (18.1%). The most prevalent diagnoses in Survey B were adjustment
      disorders (24.5%), delirium (18.8%), and depressive disorders (14.3%).
      Pharmacotherapy was the most frequent action in both surveys and accounted for
      between 45% and 49% of all actions. CONCLUSION: This study underscores the need
      for specially planned C - L services in Austria that provide both psychiatric and
      psychosocial care for patients who are medically ill.

PMID- 18827756
TI  - System identification of skin conductance response in depression - an attempt to
      probe the neurochemistry of limbic system.
AB  - OBJECTIVE: Choice of antidepressant is a daily problem in clinical work. Clinical
      predictors of therapeutic response to antidepressants are not yet available. We
      explored the possibility of using a signal analysis of skin conductance response
      (SCR) in specifying the imbalances of the neurotransmitter systems in the brain.
      SUBJECTS AND METHODS: The method consists in application of the system
      identification theory in analyzing the regulation of SCR. Eleven short stories
      from the contemporary literature have been used to elicit emotional arousal in
      subjects. Participants were divided into two groups, a group of depressed
      patients (n=57), and a healthy control group (n=52). RESULTS: The resulting
      mathematical model of SCR revealed two feedback loops. Significant differences
      have been found between depressed patients and healthy subjects in the sense of
      stronger signals in both identified feedback loops in depression. We considered
      these results in the context of the data regarding: (i) the functional
      neuroanatomy of SCR, and (ii) the neurochemical characteristics of depression.
      CONCLUSION: The methodological approach that is still to be examined could be
      useful in prediction of response to a specific antidepressant.

PMID- 18827757
TI  - Treatment of psychotic disorders with aripiprazole in the emergency psychiatric
      setting.
AB  - OBJECTIVE: To assess the effectiveness of aripiprazole in the treatment of
      patients with psychotic symptoms in the emergency psychiatric setting. SUBJECTS
      AND METHODS: We considered all patients admitted to a psychiatric intensive care
      unit of a general hospital in a two year-period, treated with at least one dose
      of aripiprazole. We measured 1) the rate of cases starting aripiprazole who did
      not change antipsychotic in the course of hospitalization; 2) the rate of cases
      who were concurrently treated with another antipsychotic; 3) the CGI Improvement
      score. RESULTS: In 63 cases, aripiprazole was started on admission. Forty-nine
      (77.7%) of these cases were treated with aripiprazole also on discharge. Among
      the 63 cases who started aripiprazole on admission, 22 (34.9%) were concurrently
      treated with another antipsychotic. Among the 53 cases discharged with
      aripiprazole, 15 (28.3%) were concurrently treated with another antipsychotic. Of
      the 49 cases treated with aripiprazole both on admission and on discharge, 24
      cases were much improved, 11 cases moderately improved, 10 cases mildly improved,
      and 4 cases were not improved at the CGI Improvement Score. CONCLUSIONS:
      Aripiprazole should be considered as first line treatment in some patients
      affected by psychotic disorders visited in the emergency psychiatric setting.

PMID- 18827758
TI  - Treatment of generalized tardive dystonia with clozapine.
AB  - Tardive dystonia is a syndrome of sustained muscle contractions, frequently
      causing twisting and repetitive movements or abnormal postures, associated with
      prolonged exposure to antipsychotics. We report a case of a 35-year-old patient
      with schizophrenia who developed a generalized form of tardive dystonia after
      switching of clozapine to risperidone treatment that persisted after switch to
      olanzapine and during the period while treatment with an antipsychotic was
      discontinued. It was successfully managed with reintroduction of clozapine. The
      case may represent the first report of generalized tardive dystonia while taking
      risperidone. The possible pathophysiological bases of the disorder are discussed.
      The goal of our report is to emphasize that an adequate trial of clozapine is a
      worthwhile option in the cases of tardive dystonia, even where discontinuation of
      antipsychotics was unsuccesful.

PMID- 18827759
TI  - Penile self-mutilation - two cases in one family.
AB  - Male genital self-mutilation is an infrequently reported event in the general
      medical literature. The majority of cases deal with a single episode of self
      mutilation. These cases are usually focused on surgical repair. We present an
      extremely rare situation of two cases of male genital self-mutilation occurring
      in the same family. Both patients were treated for schizophrenia. Both patients
      had religious psychotic experiences and guilt feelings associated with sexual
      conflicts. Both patients had an experience of setting fire. Although they were
      close relatives, the younger did not imitate the older one when he mutilated his
      genitals. The possible causes of such behavior have been analyzed in the light of
      the recent literature.

PMID- 18827760
TI  - On patient centred psychiatry.

PMID- 18827761
TI  - Transdisciplinary holistic integrative psychiatry - a wishfull thinking or
      reality?
AB  - Modern psychiatry in the last century proposed several aggregative
      biopsychosocial models as an opposition to prevailing fragmentary, reductionistic
      and dogmatic approaches. Although the biopsychosocial approach has become the
      mainstream concept of the present-day psychiatry, it is not fruitful enough
      because it is excessively broad and provides no real complex field integration
      and guidance to clinicians and researchers. The postmodern psychiatry
      alternatives have been appeared as pluralism and integrationism. Holistic and
      integrative approach in medicine and psychiatry is built on the premise that
      human beings in health and disease are complex systems of dinamically interacting
      biological, psychological, social, energetic, informational and spiritual
      processes. Emerging as a transdisciplinary holistic, complementary and
      integrative psychiatry implies widely accepted general systems theory on
      psychopathology, novel integrating interpretative models, new integrative
      understanding of etiopathogenesis or meanings of symptoms, and novel integrative
      assessment and treatment approaches addressing those etiopathogenesis and
      meanings.

PMID- 18827762
TI  - Integrative treatment in psychiatry.
AB  - Psychiatry is a medical discipline addressing the study, diagnosis, treatment and
      prevention of mental disorders. Psychiatric disorders, which may be seen in
      people of all ages, involve the emotions, the will, and intellectual processes,
      verbal and non-verbal behaviour. According to current knowledge we cannot speak
      about only one cause but of the interaction of several etiological factors,
      mutually pervading and causing the mental illness. Because of this the treatment
      of mental disorders involves the complex implementation of biological, psycho
      therapeutic, and socio-therapeutic methods of treatment. The contemporary
      principle of integrative psychiatry immanently requires simultaneous treatment of
      three human components: body, mind, and spirit. The holistic approach emphasizes
      the importance of the wholeness of the human person, and the inter-dependence of
      his components.

PMID- 18827763
TI  - Integrative psychotherapy.
AB  - The main purposes of the article are to present the history of integration in
      psychotherapy, the reasons of the development integrative approaches, and the
      approaches to integration in psychotherapy. Three approaches to integration in
      psychotherapy exist: theoretical integration, theoretical eclecticism, and common
      factors in different psychotherapeutic trends. In integrative psychotherapy, the
      basic epistemology, theory, and clinical practice are based on the phenomenology,
      field theory, holism, dialogue, and co-creation of dialogue in the therapeutic
      relationship. The main criticism is that integrative psychotherapy suffers from
      confusion and many unresolved controversies. It is difficult to theoretically and
      methodologically define the clinically applied model that is based on such a
      different epistemological and theoretical presumptions. Integrative psychotherapy
      is a synthesis of humanistic psychotherapy, object relations theory, and
      psychoanalytical self psychology. It focuses on the dynamics and potentials of
      human relationships, with a goal of changing the relations and understanding
      internal and external resistances. The process of integrative psychotherapy is
      primarily focused on the developmental-relational model and co-creation of
      psychotherapeutic relationship as a single interactive event, which is not
      unilateral, but rather a joint endeavor by both the therapist and the
      patient/client. The need for a relationship is an important human need and
      represents a process of attunement that occurs as a response to the need for a
      relationship, a unique interpersonal contact between two people. If this need is
      not met, it manifests with the different feelings and various defenses. To meet
      this need, we need to have another person with whom we can establish a sensitive,
      attuned relationship. Thus, the therapist becomes this person who tries to
      supplement what the person did not receive. Neuroscience can be a source of
      integration through different therapies. We may say that both neuroscience and
      neurobiology offer yet another bridge for integration of different schools of
      thought and supports the importance of the developmental relational model during
      the developmental phases and relational process in psychotherapy in which the
      quality of therapeutic relationship is the primary healing process. Furthermore,
      the development of integrative psychotherapy in Croatia and the organization of
      the Croatian program, which is identical to the program of the European
      Association for Integrative Psychotherapy is shortly described.

PMID- 18827764
TI  - Genetics of schizophrenia in the context of integrative psychiatry.
AB  - Epidemiological studies suggest a strong heritability in schizophrenia. Positive
      family history is the greatest risk factor for developing schizophrenia. However,
      regarding the genetic factors in schizophrenia, there is a lot of the
      inconsistency (i.e. non-replication) in the literature of the associations of
      different genes with schizophrenia. The presence of a single gene is neither
      sufficient, nor necessary to cause schizophrenia. The understanding of the
      genetic basis of schizophrenia is complex. Besides different gene polymorphisms,
      numerous environmental factors, interacting with genes, contribute to
      susceptibility to schizophrenia. Such factors include the use of street drugs,
      childhood head injury, maternal infection during pregnancy, paternal age at
      conception, stressful life events and urban upbringing. While knowing genetic
      risks, integrative psychiatry may have a role in reducing other modifiable risk
      factors, including reduction of stress level, stress management strategies,
      family consultation/education, education against street drugs use, treatment of
      prodromal symptoms and development of social skills.

PMID- 18827765
TI  - CYP 2D6 polymorphism and antipsychotic therapy.
AB  - One of the most challenging problems in clinical psychiatry are inter-individual
      differences in clinical response to antipsychotic treatment. Several studies were
      investigating the impact of the polymorphic cytochrome P450 2D6 gene (CYP 2D6) on
      the psychopathological and extrapyramidal symptoms, but the results were
      conflicting. There is a lack of clinical studies of the impact of CYP2D6
      polymorphism on therapeutic efficacy, especially in the long-term treatment of
      schizophrenia. The aim of the presentation was to evaluate the impact of CYP2D6
      genotype on psychopathological and extrapyramidal symptoms in a group of
      Slovenian outpatients with schizophrenia or schizoaffective disorder in stable
      remission, who were receiving long-term maintenance therapy.

PMID- 18827766
TI  - Phospholipid membrane abnormalities and reduced niacin skin flush response in
      schizophrenia.
AB  - OBJECTIVES: Reduced n-3 and n-6 polyunsaturated fatty acids (PUFAs) content in
      red blood cell (RBC) membranes and abnormal membrane phospholipid metabolism were
      repeatedly implicated in the etiology of schizophrenia. FINDINGS: Prenatal and
      perinatal depletion of PUFAs interferes with normal brain development and
      function. The lack of docosahexaenoic acid - DHA in the brain is reflected in
      lower membrane DHA/AA (AA - arachidonic acid) ratio, increased activity of AA
      metabolizing enzymes, and disturbance of downstream metabolic pathways involved
      in signaling, growth modulation, brain glucose uptake, immune functions,
      neurotransmission, synaptogenesis and neurogenesis. Preliminary high-throughput
      metabolomic studies revealed abnormal biochemical profile in patients with
      schizophrenia or brief psychotic disorder when compared to healthy controls. The
      results of both metabolomic and proteomic studies pointed to energy metabolism
      and lipid biosynthesis being impaired in schizophrenia. The usefulness of
      antipsychotic medication and supplementation with PUFAs in reverting to the
      normal metabolic state has been suggested in early treatment of the first
      psychotic episode. Abnormalities of phospholipid metabolism can be also detected
      as attenuated niacin skin flush response in the variety of neuropsychiatric
      disorders. CONCLUSIONS: Disturbances of lipid homeostasis could represent
      biochemical markers in the preclinical phase of neuropsychiatric illnesses and
      could serve as triggers in genetically vulnerable individuals. The assessment of
      patients' lipid status may also help in monitoring the course of the disease and
      treatment response. In this regard, simple, cheap and fast niacin skin flush test
      might be valuable. It might help in diagnosis of adolescents and young adults
      with psychotic behaviour, or in defining the necessity for long-term
      antipsychotic therapy. Along with antipsychotic medication schizophrenic patients
      need specific medical nutrition therapies.

PMID- 18827767
TI  - Metabolic syndrome and schizophrenia from integrative medicine perspective.
AB  - BACKGROUND: There has been a growing interest in the effect that comorbid
      schizophrenia and metabolic syndrome may have on each other. OBJECTIVE: To
      examine metabolic syndrome from integrative medicine point of view including
      prevalence of metabolic syndrome in patients with schiziphrenia compared to their
      first-degree relatives, healthy volunteers without schizophrenia in close family,
      and patients with PTSD, as well as the percentage patients with schizophrenia
      without any component of metabolic syndrome. METHOD: Metabolic syndrome according
      to NCEP/ATP III criteria and number of its components were analysed in 205
      patients with schizophrenia, 140 healthy volunteers and 105 patients with combat
      PTSD. RESULTS: Metabolic syndrome was identified in 45.9% of the patients with
      schizophrenia, 38.1% of the war veterans with PTSD, 36.7% of the first-degree
      relatives of patients with schizophrenia and 16.2% of the healthy volunteers
      without schizophrenia in close family. Only 21.5% of the patients with
      schizophrenia were without any metabolic syndrome component. CONCLUSION: The
      comorbidity of schizophrenia and metabolic syndrome is very important for theory
      and practice of integrative medicine. Almost 80% of the patients with
      schizophrenia have increased risk or developed cardiovascular disorders,.

PMID- 18827768
TI  - Association of cholesterol and socio-demographic parameters with suicidality in
      the male patients with schizophrenia.
AB  - Suicidal behavior is a major health risk in schizophrenia. The aim of this study
      was to evaluate serum cholesterol concentrations and some socio-demographic
      parameters in suicidal and non-suicidal men suffering from schizophrenia. Results
      of this study show that there were no differences in socio-demographic parameters
      between suicidal and non-suicidal schizophrenic patients but there was a
      difference in the level of cholesterol (lower in suicidal patients). Duration of
      untreated psychosis was higher in suicidal patients, which could means that
      suicidality is a process determined by many different factors including time of
      treatment. Suicidal patients in our study have been more seriously ill than non
      suicidal (had higher scores on PANNS and HDRS-17) and we explained these findings
      by the fact of damage associated to higher time of non-treatment. Our results
      show that cholesterol has an important role in distinguishing suicidal from non
      suicidal patients, which, if confirmed on a higher number of patients and in more
      studies, may be of considerable clinical significance. Clinical management of
      suicidal states is based on integrative approach and includes ensuring immediate
      safety, the use of psychosocial techniques to address depression and psychosocial
      stressors, and targeted pharmacotherapy for psychotic and depressive symptoms.

PMID- 18827769
TI  - Schizoaffective disorder: from Kraepelin to genes.
AB  - The original term schizoaffective disorder was invented 75 years ago by Kasanin
      as a response to diagnostic difficulty with patients who did not fit well in
      Kraepelin's dichotomy of dementia praecox and affective disorder. However, this
      was not the perfect solution since criteria for diagnosing schizoaffective
      disorder were not firmly set at that time. The broad category of schizoaffective
      disorders included not only patients with co-occurring schizophrenic and
      affective symptoms but also other "atypical" psychoses. Over time diagnostic
      criteria became more defined but the original question still remains the same: is
      there any such thing as schizoaffective disorder? This paper presents some
      historical and modern data which may help clarify this issue, but it is still
      premature to give a definitive answer on all pending questions related to this
      interesting topic.

PMID- 18827770
TI  - Pharamacogenetics and antidepressant treatment in integrative psychiatry
      perspective.
AB  - The concept of individualized drug therapy on the basis of pharmacogenetics has
      become a central focus in the treatment of depression. There is an increasing
      agreement about the importance of polymorphisms in cytochrome P450 enzymes and
      the effects of drug-drug interactions in relation to the incidence of adverse
      effects. There has been also increasing focus on the role of the drug transporter
      P-glycoprotein (P-gp) with regard to drug penetration into the brain. P-gp at the
      blood-brain barrier can exert a profound effect on the ability of some
      antidepressants to enter the brain. In addition, genetic polymorphism of the
      serotonin transporter has been investigated in relationship to the therapeutic
      response to several antidepressants, especially SSRIs. However, prediction of
      response on the basis of variants of candidate genes is incipient and remains
      elusive.

PMID- 18827771
TI  - Countertransference in the therapy of suicidal patients - an important part of
      integrative treatment.
AB  - One of the central issues in the psychotherapy of suicidal patients is the
      countertransference. Key concepts in countertransference include projective
      identification, role-responsiveness and countertransference enactment. It is
      important to recognize that countertransference can be effective in understanding
      the emotional intensity of the suicidal person's internal world. There is a
      significant relationship between treatment outcome and the different
      countertransference feelings among the therapists. In this paper we have
      illustrated important factors for understanding psychiatrist's
      countertransference reactions when working with suicidal patients.

PMID- 18827772
TI  - Metabolic syndrome and depression in war veterans with post-traumatic stress
      disorder.
AB  - BACKGROUND: Post-traumatic stress disorder (PTSD), depression and metabolic
      syndromes are growing public health problems in post-war countries. Understanding
      the co-morbidity among PTSD, depression and metabolic syndrome has an important
      clinical and theoretical issue. OBJECTIVE: To examine the relationship between
      combat-related PTSD, co-morbid depression and metabolic syndrome as well as
      between severity of depression and metabolic syndrome. METHOD: Metabolic syndrome
      and co-morbid depression were investigated in 100 male war veterans with combat
      PTSD and in 79 males who needed medical attention in dispensary of family
      medicine. RESULTS: Metabolic syndrome according NCEP: ATP III was found in 25 %
      of war veterans with PTSD. Metabolic syndrome was identified more frequently in
      PTSD patients with co-morbid depression (47.8 %) compared to those without
      depression (9.1%). PTSD with moderate and severe co-morbid depression was
      associated with higher rates of metabolic syndrome (78.6% and 90.9% respectively)
      in comparison with mild depression (26.2%). CONCLUSIONS: PTSD is frequently
      comorbid with depression, and when the two disorders co-occur, the risk for
      metabolic syndrome is increased. Treatment of war veterans with PTSD should
      address co-morbid depression and metabolic syndrome as well as the clinical
      features of PTSD.

PMID- 18827773
TI  - Emotional stress as a trigger in sudden cardiac death.
AB  - The influence of anxiety and depression on cardiovascular disease is well-known
      in terms of chronic cardiovascular and ischemic states. It happens mostly through
      diminished cardiac vagal modulation and greater procoagulant activity in
      depressed patients. But the impact of emotional factors in acute cardiac events
      is not estimated enough. From the clinician's point of view, there are an
      increasing awareness concerning external circumstances and external triggering in
      sudden cardiac death, that is caused by malignant ventricular arrhythmias or
      myocardial infarction. A number of external, i.e. exogenous factors in everyday
      life can be implicated in triggering such events. Including heavy physical
      activity, emotional stressors, meteorologic variables, air pollutants,
      chronobiologic phenomena, food ingestions, coffee, alcohol etc., emotional stress
      seems to be among the most often triggers of sudden event. There is a wide range
      of everyday situations and activities that involves activation of sympathetic
      nervous system, and emotional stressors are described as trigger caused by
      sympathetic arousal. Acute emotional arousal can trigger life-threatening
      arrhythmias and the mechanisms of that risk have been recognized. Acute episode
      of emotional distress (and notably anger-like stress) may trigger ventricular
      ectopic beats and tachycardia, as well as acute myocardial infarction. These
      sudden phenomena can be the result of the endogenous response to external risk of
      acute emotional stress. Sudden death without antecedent angina, suggesting
      cardiac arrhythmia, as well as deaths preceded by chest pain, suggesting coronary
      occlusion were observed in many studies that have led to estimates that between
      20 and 40 percent of sudden cardiac deaths are precipitated by acute emotional
      stressors.

PMID- 18827774
TI  - Basic aspects of psychodermatology.
AB  - Psychodermatological or psychocutaneous disorders are conditions resulting from
      the interaction between the mind and the skin. There are three major groups of
      psychodermatological disorders; psychophysiologic disorders, psychiatric
      disorders with dermatologic symptoms, and dermatologic disorders with psychiatric
      symptoms. Along with the standard dermatological treatment, majority of these
      disorders can be treated with cognitive-bihevioral psychotherapy,
      psychoterapeutic stress-and-anxiety-management technicques and psychotropic
      drugs. Therefore, understanding of biopsychosocial approaches and liaison
      approach involving general practice, psychiatrist, dermatologist and psychologist
      treatment in this field is essential.

PMID- 18827775
TI  - Depression in dermatology: an integrative perspective.
AB  - An example which confirmes the adequacy of the integrative perspective in
      medicine is depression in dermatology because of the sufficient number of
      arguments linking depression and some chronic skin conditions in depth more than
      simply comorbidity. In recent literature, the authors found, how depression in
      dermatology occurs significantly more frequently than in the general population.
      In dermatological patients the prevalence of depression is around 30% which is
      more in comparison to patients in general practice where prevalence of depression
      is 22%. The authors found a considerable similarity in the various
      characteristics between depression and psoriasis, based upon recent research
      findings in immunity disorder and elevated concentrations of proinflammatory
      cytokines as well as acute phase proteins in both disorders, indicating that both
      disorders can be considered as immunologicaly mediated, inflammatory states with
      repetitive chronic progress and similar comorbidity. The afore mentioned
      theoretical settings evoke the integrative aspect and the integrative
      interdisciplinary approach placing in the center of attention not only the
      diseased person with his fears, needs, preocupations and expectations during
      treatment, but the person who is at risk of becoming burdened with these
      disorders.

PMID- 18827776
TI  - The role and importance of consulting psychiatry in paediatric surgery.
AB  - The main aim of this study was to point on role and importance of consulting
      psychiatry in paediatric population of patients particularly in branch of
      paediatric surgery. This study is a view to a few years research on
      biopsychosocial aspect of treatment of long bones fractures in children and
      adolescents realized in Departments for paediatric surgery of three hospitals, in
      Zagreb and Rijeka, Croatia, as well as in Mostar, Bosnia and Herzegovina, in
      period 2003.-2007. There have been investigated 135 patients, both gender, 10-18
      years of age differently treated for long bones limbs' fractures. Basic methods
      of work were self-reported questionnaires to evaluate the degree of self-esteem,
      depression, anxiety, quality of life and perception of social support in
      mentioned patients. Our results pointed at the influence of type of treatment of
      long bones fractures on psychological variables, mostly on self-esteem and self
      perception of quality of life. As a conclusion, we suggest the possibility of
      psychological preparation of the patients in order to diminish the psychological
      reaction to the surgical treatment, as well as individual consulting (liaison)
      psychiatric intervention during the treatment of fractures of long bones
      according to the individual needs.

PMID- 18827777
TI  - Position and role of forensic psychiatry in integrative psychiatry.
AB  - The integrative approach to psychiatry has gained more importance in recent
      years. Is it justified or not, does it improve theory or practice, those are only
      some of the questions to which we are looking for answers, but in this paper we
      shall underline the necessity of enrolling forensic psychiatry into integrative,
      modern psychiatry. The reason and the motive for that integration is the fact
      that nowadays the content and the activities of contemporary forensic
      psychiatrists are totally reduced to executing the tasks given by courts. It is
      therefore entirely right to say that current forensic psychiatry finds itself in
      the passive role of executing orders of the court. Our aim is to point out how
      important it is that forensic psychiatry becomes an interdisciplinary profession
      in interaction with psychiatry but also with other medical branches just as with
      judiciary, educational institutions, moral-ethical institutions and religious
      institutions in producing preventive programmes and by participating in
      individual decision making process likewise. Our primary goal is to present the
      status and the position of contemporary forensic psychiatry and to specify the
      necessary improvements and its place in integrative psychiatry. It should be
      better, more meaningful and more ethical, both for the individual and the society
      in total. We want forensic psychiatry to include a protective and therapeutic
      role for each individual forensic examinee, i.e. a person who has already been in
      forensic examination and for whom one evaluates mental competence because of a
      mental disorder. We also want it to get a far larger and more active general role
      in society in terms of preventing criminal acts among the mentally ill and in
      society in total.

PMID- 18827778
TI  - (Re)Integration of mental patients - mixed media messages.
AB  - It can be said that (re)integration of mental patients is the basic goal of
      psychiatry as a medical discipline. Throughout the history of psychiatry
      different approaches to treatment and rehabilitation of mental patients and their
      social (re)integration have been identified and monitored. There have always
      existed different impediments to the (re)integration of mental patients, as a
      manifestation of the times when treatment and rehabilitation took place. In the
      beginning of psychiatric development, the principal goal, in line with the social
      development and social awareness of human rights, was to isolate the patient away
      from his/her social environment and place him/her into a psychiatric hospital,
      preferably for life. Lately, as fighting for human rights grew into a matter of
      fashion and prestige rather than an ethical and legal issue, the media have often
      spoken about the human rights of mental patients and, explicitly or implicitly,
      advocated their social (re)integration. This cry for human rights of mental
      patients has virtually rooted out the advocates for permanent social isolation,
      even in this region. However, the Croatian media often give out the so called
      mixed messages when it comes to treating mental patients. This article analyzes
      such contradictory communication and attempts to offer certain solutions.

PMID- 18827779
TI  - Religiosity and schizophrenia.
AB  - We focus on the relationships between schizophrenia and religiosity, on the basis
      of the review of literature and the data of an ongoing study about religiousness
      and personality, and religious coping conducted among outpatients with
      schizophrenia. Religion may be part of the psychopathology, but some of its
      dimensions may be protective from the negative effects of the illness. Religion
      may be relevant for the treatment of people with schizophrenia in that it may
      help to reduce pathology, to enhance coping and to foster recovery. Religiosity
      is multidimensional concept and so it must be evaluated in the people with
      schizophrenia (Aukst-Margetic et al. 2005).

PMID- 18827780
TI  - Assessment of mental health services in Slovenia with The European Service
      Mapping Schedule.
AB  - The aim of our study was to examine availability and utilization of mental health
      services in the 12 Slovenian statistical regions by using the The European
      Service Mapping Schedule (ESMS) methodology. 251 mental health services were
      mapped according to their type as presented in schema of ESMS service tree.
      Marked differences between regions were noticed in patterns of service provision
      and utilization. In contrast with the scarcity of mental health services in the
      Zasavska and Notranjsko-kraska region, the Central-Slovenian region offered the
      most diverse and abundant choice of services of all statistical regions. We lack
      day and structured activity services offering work or work-related activities.
      Out-patient and community services are mainly medium intensity non-mobile
      services that offer continuing care.

PMID- 18827781
TI  - Mental illness and ethnicity - being a stateless person (apatride).
AB  - The main aim of this study has been to perceive the state of mentally ill
      stateless person hospitalized in Psychiatric Hospital Rab, Croatia with forensic
      status. This is a case report of such a person, F.V., 25 years old female, with
      no documents and other affirmed auto and heteroanamnestic data. Her psychical
      state and ability of communication do not allow realization of certain
      autoanamnesis and in the same time she has no family or relatives to give
      heteroanamnestic data. It is also unknown exact date and place of birth. Only
      certain data were that she lived in many orphanages, refugees' camps and communes
      in several European countries. She immigrated illegally in Croatia where she has
      made some criminal acts and earned forensic status. We tried to evaluated the
      complex status of our patient from several points of view and tried to answer to
      the questions where to start and what to do with such a person to do the best for
      her and including her human rights. As a conclusion, we could say that holistic
      and individual approach to such patients has been necessary with engagement of
      many profiles of professionals.

PMID- 18827785
TI  - Bendamustine: a new therapeutic option for hematologic malignancies.

PMID- 18827786
TI  - Advances in defective mismatch repair colon cancer.

PMID- 18827787
TI  - Testing for thrombophilias.

PMID- 18827788
TI  - Cardiovascular toxicity of new agents.

PMID- 18827789
TI  - Adjuvant therapy for HER2 positive breast cancer: are anthracyclines still
      necessary?
AB  - Anthracyclines are integral components of most adjuvant chemotherapy regimens for
      surgically removed early breast cancer and are central to the accepted treatment
      standards. Recently the standard anthracycline regimen of doxorubicin plus
      cyclophosphamide was found to be inferior in preventing recurrence of breast
      cancer when compared to cyclophosphamide and docetaxel, questioning the necessity
      to expose patients to the potential cardiotoxicity of anthracycline in the
      adjuvant setting. Trastuzumab, a humanized monoclonal antibody against the
      extracellular domain of the human epidermal growth factor receptor 2 (HER2) has
      become the cornerstone of treatment of breast cancers that overexpress HER2 in
      the neo-adjuvant and metastatic setting. Unfortunately, the combination of
      anthracyclines and trastuzumab produces a high incidence of cardiotoxicity as
      seen in early trials of metastatic breast cancer. Five adjuvant trials combining
      trastuzumab with different anthracycline-based regimens have been reported, all
      of them revealing similar efficacy in reducing recurrence of breast cancer. The
      trastuzumab adjuvant trial 006 from the Breast Cancer International Research
      Group shows for the first time that a nonanthracycline-containing regimen with
      trastuzumab has equivalent efficacy in decreasing the recurrence of breast
      cancer, with less incidence of cardiotoxicity when compared to anthracycline
      containing trastuzumab adjuvant regimens. Further trials are needed to determine
      the optimal length of adjuvant therapy with trastuzumab, as well as long-term
      side effects with special attention to cardiotoxicity.

PMID- 18827790
TI  - What is imatinib-resistant chronic myeloid leukemia? Identifying and managing
      loss of response.
AB  - Imatinib is widely recognized as the standard of care in the first-line treatment
      of chronic myeloid leukemia (CML); however, resistance can limit its long-term
      benefits. Early identification of the loss of response to imatinib is therefore
      important for the optimal management of patients with this type of leukemia.
      Cytogenetic and molecular responses during the first 12 months of treatment have
      been shown to predict future responses (complete cytogenetic response and major
      molecular response) and reduce disease progression. The degree of early reduction
      in BCR-ABL levels after commencing imatinib therapy is a good indicator of
      subsequent response. Monitoring for kinase domain mutations should also be
      considered in patients with suboptimal response or in those who demonstrate
      resistance. Modification of the treatment strategy is required if there is a loss
      of response. Dasatinib and nilotinib are the most extensively studied second
      generation BCR-ABL tyrosine kinase inhibitors, and are currently approved for
      treating patients following imatinib failure.

PMID- 18827791
TI  - Fibromatosis of the breast after mammary prosthesis implantation.

PMID- 18827792
TI  - Review: aggressive fibromatosis and breast implant.

PMID- 18827794
TI  - Stop making sense!

PMID- 18827796
TI  - Vitamin D in chronic kidney disease: is the jury in?
AB  - Vitamin D shows promise for improving diverse health outcomes among patients with
      chronic kidney disease. Observational studies of vitamin D medications have
      contributed important evidence for broad beneficial clinical effects of vitamin D
      beyond actions on bone. However, such studies are limited by the potential for
      confounding by indication. A large randomized controlled trial is now needed to
      test the hypothesis that vitamin D therapy improves clinical outcomes in patients
      with kidney disease.

PMID- 18827797
TI  - The hunt for the perfect biomarker for acute kidney injury: back to gamma-trace?
AB  - The hunt for a good biomarker for acute kidney injury (AKI) is currently hot. It
      has recently been the subject of several excellent reviews(1, 2 and 3) and a
      useful meta-analysis,(4) and we are hearing exhortations that this hunt should
      get high priority.(3, 5) The ideal marker (or set of markers) should facilitate
      early identification, stratify risk, and contribute to informative diagnostic
      classification. Perhaps most importantly, a good marker should aid the testing of
      interventions to prevent development of AKI and improve management. So, there are
      very good reasons to get on with it!

PMID- 18827798
TI  - Preservation of the kidney by carbon monoxide: a black swan phenomenon.
AB  - Nakao and colleagues demonstrate that carbon monoxide added to organ preservation
      solution reduces donor-kidney injury that occurs after cold storage and
      transplantation and improves the survival of the recipient. These findings are
      important because they highlight the role of the cytochrome P450 system in the
      pathogenesis of donor-kidney injury and they suggest a strategy for preserving
      the donor kidney, namely, the addition of carbon monoxide to organ preservation
      solution.

PMID- 18827799
TI  - Animal models of sepsis and its complications.
AB  - Most currently used animal sepsis models fail to adequately replicate the
      clinical problem and, therefore, have only limited utility for investigating
      pathophysiological mechanisms or testing the efficacy of new therapeutic agents.
      Recent experimental findings support this view and suggest that models of acute
      infection in mice with pre-existing renal dysfunction may be useful in the
      development pathway for new therapeutic agents for sepsis.

PMID- 18827800
TI  - The impact of sodium chloride and volume depletion in the chronic kidney disease
      of congenital chloride diarrhea.
AB  - Congenital chloride diarrhea is due to mutations in the intestinal Cl(-)/HCO(3)(
      ) exchange (SLC26A3) which results in sodium chloride and fluid depletion leading
      to hypochloremic and hypokalemic metabolic alkalosis. Although treatment with
      sodium and potassium chloride offers protection from renal involvement in
      childhood, the long-term renal outcome remains unclear. Here we describe two
      cases of congenital chloride diarrhea-associated end-stage renal disease with
      transplantation. Further, we show that there is a high incidence of mild chronic
      kidney disease in 35 other patients with congenital chloride diarrhea. The main
      feature of the renal injury was nephrocalcinosis, without hypercalciuria or
      nephrolithiasis with small sized kidneys and commensurately reduced glomerular
      filtration rates. This suggests that diarrhea-related sodium chloride and volume
      depletion, the first signs of non-optimal salt substitution, promote urine
      supersaturation and crystal precipitation. The poor compliance with salt
      substitution along with long-lasting hypochloremic and hypokalemic metabolic
      alkalosis is likely to induce progressive calcification and renal failure. Both
      our patients developed nephrocalcinosis in the transplanted kidneys suggesting
      that this complication is a consequence of intestinal SLC26A3 deficiency.
      Interestingly, the transporter is expressed in the distal nephron but the
      recurrence of nephrocalcinosis in the transplanted kidney suggests that it does
      not play a significant renal role in this syndrome.

PMID- 18827801
TI  - The Case: Milky urine. Chyluria.

PMID- 18827802
TI  - Actinomyces abscess in a patient with Wegener's granulomatosis.

PMID- 18827803
TI  - Chitosan/siRNA nanoparticle-mediated TNF-alpha knockdown in peritoneal
      macrophages for anti-inflammatory treatment in a murine arthritis model.
AB  - Secretion of tumor necrosis factor-alpha (TNF-alpha) by macrophages plays a
      predominant role in the development and progression of rheumatoid arthritis. We
      demonstrate that knockdown of TNF-alpha expression in systemic macrophages by
      intraperitoneal (i.p.) administration of chitosan/small interfering RNA (siRNA)
      nanoparticles in mice downregulates systemic and local inflammation. Chitosan
      nanoparticles containing an unmodified anti-TNF-alpha Dicer-substrate siRNA
      (DsiRNA) mediated TNF-alpha knockdown (approximately 66%) in primary peritoneal
      macrophages in vitro. The presence of Cy3-labeled nanoparticles within peritoneal
      macrophages and specific TNF-alpha knockdown (approximately 44%) with TNF-alpha
      siRNA after i.p. injection supports our therapeutic approach. Downregulation of
      TNF-alpha-induced inflammatory responses arrested joint swelling in collagen
      induced arthritic (CIA) mice dosed i.p. with anti-TNF-alpha DsiRNA nanoparticles.
      The use of 2'-O-Me-modified DsiRNA resulted in the lowest arthritic scores and
      correlated with reduced type I interferon (IFN) activation in macrophages in vivo
      compared with unmodified DsiRNA. Histological analysis of joints revealed minimal
      cartilage destruction and inflammatory cell infiltration in anti-TNF-alpha
      treated mice. The onset of arthritis could be delayed using a prophylactic dosing
      regime. This work demonstrates nanoparticle-mediated TNF-alpha knockdown in
      peritoneal macrophages as a method to reduce both local and systemic
      inflammation, thereby presenting a novel strategy for arthritis treatment.

PMID- 18827804
TI  - A single intravenous injection of adeno-associated virus serotype-9 leads to
      whole body skeletal muscle transduction in dogs.
AB  - The success of many gene therapy applications hinges on efficient whole body
      transduction. In the case of muscular dystrophies, a therapeutic vector has to
      reach every muscle in the body. Recent studies suggest that vectors based on
      adeno-associated virus (AAV) are capable of body-wide transduction in rodents.
      However, translating this finding to large animals remains a challenge. Here we
      explored systemic gene delivery with AAV serotype-9 (AAV-9) in neonatal dogs.
      Previous attempts to directly deliver AAV to adult canine muscle have yielded
      minimal transduction due to a strong cellular immune response. However, in
      neonatal dogs we observed robust skeletal muscle transduction throughout the body
      after a single intravenous injection. Importantly, systemic transduction was
      achieved in the absence of pharmacological intervention or immune suppression and
      it lasted for at least 6 months (the duration of study). We also observed several
      unique features not predicted by murine studies. In particular, cardiac muscle
      was barely transduced in dogs. Many muscular dystrophy patients can be identified
      by neonatal screening. The technology described here may lead to an effective
      early intervention in these patients.

PMID- 18827805
TI  - High-throughput screening and biophysical interrogation of hepatotropic AAV.
AB  - We set out to analyze the fundamental biological differences between AAV2 and
      AAV8 that may contribute to their different performances in vivo. High-throughput
      protein interaction screens were used to identify binding partners for each
      serotype. Of the >8,000 proteins probed, 115 and 134 proteins were identified
      that interact with AAV2 and AAV8, respectively. Notably, 76 of these protein
      interactions were shared between the two serotypes. CDK2/cyclinA kinase was
      identified as a binding partner for both serotypes in the screen. Subsequent
      analysis confirmed direct binding of CDK2/cyclinA by AAV2 and AAV8. Inhibition of
      CDK2/cyclinA resulted in increased levels of vector transduction. Biophysical
      study of vector particle stability and genome uncoating demonstrated slightly
      greater thermostability for AAV8 than for AAV2. Heat-induced genome uncoating
      occurred at the same temperature as particle degradation, suggesting that these
      two processes may be intrinsically related for adeno-associated virus (AAV).
      Together, these analyses provide insight into commonalities and divergences in
      the biology of functionally distinct hepatotropic AAV serotypes.

PMID- 18827806
TI  - Persistent expression of PEDF in the eye using high-capacity adenovectors.
AB  - Ocular neovascularization, the growth of abnormal blood vessels in the eye, is a
      factor shared by the most common blinding diseases in developed countries.
      Pigment epithelium-derived factor (PEDF) is a potent antiangiogenic and
      neuroprotective protein that is normally produced in the eye. When delivered via
      an adenovector, PEDF can block the growth of new blood vessels and trigger the
      selective regression of abnormal vessels in animal models of ocular disease.
      Because of the absence of adenoviral genes, high-capacity (HC) adenovectors offer
      the potential for persistent transgene expression and enhanced tolerability. We
      have assessed the durability of PEDF expression and the induction of ocular
      inflammation following delivery of a PEDF-expressing HC adenovector compared to
      earlier generation vectors. The HC vector mediated prolonged PEDF expression in
      tissue-cultured pigmented epithelial cells and when delivered by intravitreal
      injection into the mouse eye. Delivery of first-generation adenovectors resulted
      in a dose-dependent increase in cytokine/chemokine gene expression, which
      correlated with the infiltration of inflammatory cells in the eye. In comparison,
      the levels of inflammatory gene expression and the intraocular infiltrate were
      substantially reduced following delivery of the HC vector. These results support
      the development of the HC adenovector gene delivery system for ocular disease.

PMID- 18827807
TI  - Use of biological therapy to enhance both virotherapy and adoptive T-cell therapy
      for cancer.
AB  - To protect viral particles from neutralization, sequestration, nonspecific
      adhesion, and mislocalization following systemic delivery, we have previously
      exploited the natural tumor-homing properties of antigen-specific CD8+ T cells.
      Thus, OT-I T cells, preloaded in vitro with the oncolytic vesicular stomatitis
      virus (VSV), can deliver virus to established B16ova tumors to generate
      significantly better therapy than that achievable with OT-I T cells, or
      systemically delivered VSV, alone. Here, we demonstrate that preconditioning
      immune-competent mice with Treg depletion and interleukin-2 (IL-2), before
      adoptive T-cell therapy with OT-I T cells loaded with VSV, leads to further
      highly significant increases in antitumor therapy. Therapy was associated with
      antitumor immune memory, but with no detectable toxicities associated with IL-2,
      Treg depletion, or systemic dissemination of the oncolytic virus. Efficacy was
      contributed by multiple factors, including improved persistence of T cells;
      enhanced delivery of VSV to tumors; increased persistence of OT-I cells in vivo
      resulting from tumor oncolysis; and activation of NK cells, which acquire potent
      antitumor and proviral activities. By controlling the levels of virus loaded onto
      the OT-I cells, adoptive therapy was still effective in mice preimmune to the
      virus, indicating that therapy with virus-loaded T cells may be useful even in
      virus-immune patients. Taken together, our data show that it is possible to
      combine adoptive T-cell therapy, with biological therapy (Treg depletion+IL-2),
      and VSV virotherapy, to treat established tumors under conditions where none of
      the individual modalities alone is successful.

PMID- 18827808
TI  - VEGF and Delta-Notch: interacting signalling pathways in tumour angiogenesis.
AB  - Tumour angiogenesis has become an important target for antitumour therapy, with
      most current therapies aimed at blocking the VEGF pathway. However, not all
      tumours are responsive to VEGF blockers, and some tumours that are responsive
      initially may become resistant during the course of treatment, thus there is a
      need to explore other angiogenesis signalling pathways. Recently, the Delta-Notch
      pathway, and particularly the ligand Delta-like 4 (Dll4), was identified as a new
      target in tumour angiogenesis. An important feature in angiogenesis is the
      manifold ways in which the VEGF and Delta-Notch pathways interact. The emerging
      picture is that the VEGF pathway acts as a potent upstream activating stimulus
      for angiogenesis, whereas Delta-Notch helps to guide cell fate decisions that
      appropriately shape the activation. Here we review the two signalling pathways
      and what is currently known about the ways in which they interact during tumour
      angiogenesis.

PMID- 18827809
TI  - Tallness is associated with risk of testicular cancer: evidence for the nutrition
      hypothesis.
AB  - The pathogenesis of testicular germ cell tumours (GCTs) is potentially influenced
      by high-energy nutrition during infancy. As adult height is a proxy for childhood
      nutrition, we investigated the role of nutrition in GCT pathogenesis by comparing
      stature of patients with healthy men. In a matched case-control study, 6415
      patients with GCT were compared with healthy army conscripts (1:6 matching modus)
      with regard to height (cm) and body mass index (BMI; kg/m(2)). Statistical
      analysis involved tabulation of descriptive height measures and BMI. Conditional
      logistic regression models were used to quantify the association of GCT with
      height, with odds ratios (OR) adjusted for BMI. The literature was searched for
      studies on stature in GCT patients. Body size is significantly associated with
      risk of GCT, very tall men (>195 cm) having a GCT risk of OR=3.35 (95% confidence
      intervals (CI): 2.88-3.90; adjusted). Short stature is protective (OR=0.798; 95%
      CI: 0.68-0.93). Both histologic subgroups are associated with tallness. Of 16
      previous reports, 7 were confirmative, 5 had null and 4 equivocal results. The
      association of stature with GCT risk accords with the nutrition hypothesis of
      GCT. This study expands the current view of GCT tumorigenesis by suggesting that
      high-calorie intake in childhood promotes GCT precursors originating in utero.

PMID- 18827810
TI  - Neonatal growth and breast cancer risk in adulthood.
AB  - Birth size of a woman has been positively associated with her breast cancer risk,
      particularly before menopause, but no study has investigated neonatal growth in
      relation to this risk. We conducted a case-control study nested within a
      population-based cohort of women, born in Sweden between 1901 and 1961, covering
      all 405 breast cancer patients and 1081 age- and hospital-matched controls, who
      were born after newborn charts became available. Compared to neonates who lost
      <200 g after birth and grew at a rate <25 g day(-1) after reaching postnatal
      weight nadir (ie, the minimum, before starting to regain weight), those who
      either lost >/=200 g after birth or grew >/=25 g day(-1) after nadir, or both,
      were at an approximately 50% increased breast cancer risk. The excess risk was
      striking and statistically significant among women below 50 years of age, but was
      not evident among older women. Immediate postnatal weight loss (an indicator of
      water loss, likely to reflect water retention associated with pregnancy hormones)
      as well as neonatal weight gain rate after the nadir (known to reflect growth
      hormone levels) was significantly positively associated with premenopausal breast
      cancer risk.

PMID- 18827811
TI  - Dietary calcium and vitamin D intakes in childhood and throughout adulthood and
      mammographic density in a British birth cohort.
AB  - We examined the role of dietary calcium and vitamin D intakes in childhood and
      throughout adulthood in relation to mammographic density using data from a
      nationally representative cohort of 1161 women followed up since their birth in
      1946. Dietary intakes at the age of 4 years were determined by 24-h recalls and
      at the ages of 36, 43 and 53 years by 5-day food records. After adjusting for
      known risk factors and confounders, no evidence of a relationship between dietary
      calcium or vitamin D intakes and mammographic density approximately at the age of
      50 years was found, except for a cross-sectional relationship between dietary
      calcium intake at the age of 53 years and breast density in women who were post
      menopausal at the time of mammography, with those in the top fifth of the
      distribution of calcium intake having a 0.53 s.d. lower percent breast density
      than those in the lowest fifth (P-value <0.01 for linear trend).

PMID- 18827812
TI  - Effects of G/A polymorphism, rs266882, in the androgen response element 1 of the
      PSA gene on prostate cancer risk, survival and circulating PSA levels.
AB  - Prostate-specific antigen (PSA) is a protease produced in the prostate that
      cleaves insulin-like growth factor binding protein-3 and other proteins.
      Production is mediated by the androgen receptor (AR) binding to the androgen
      response elements (ARE) in the promoter region of the PSA gene. Studies of a
      single nucleotide polymorphism (PSA -158 G/A, rs266882) in ARE1 of the PSA gene
      have been conflicting for risk of prostate cancer and effect on plasma PSA
      levels. In this nested case-control analysis of 500 white cases and 676 age- and
      smoking-matched white controls in the Physicians' Health Study we evaluated the
      association of rs266882 with risk and survival of prostate cancer and
      prediagnostic total and free PSA plasma levels, alone or in combination with AR
      CAG repeats. We used conditional logistic regression, linear regression and Cox
      regression, and found no significant associations between rs266882 (GG allele vs
      AA allele) and overall prostate cancer risk (RR=1.21, 95% confidence intervals
      (CI): 0.88-1.67) or prostate cancer-specific survival (RR=0.94, 95%CI: 0.56
      1.58). Similarly, no associations were found among high grade or advanced stage
      tumours, or by calendar year of diagnosis. There was no significant association
      between rs266882 and baseline total or free PSA levels or the AR CAG repeats, nor
      any interaction associated with prostate cancer risk. Meta-analysis of 12 studies
      of rs266882 and overall prostate cancer risk was null.

PMID- 18827813
TI  - Adiponectin differentially affects gene expression in human mammary epithelial
      and breast cancer cells.
AB  - Serum levels of adiponectin are inversely associated with breast cancer risk. In
      this study, its effect on growth and gene expression of MCF-7 breast cancer cells
      and MCF-10A human mammary epithelial cells was compared. The antiproliferative
      effect of adiponectin on MCF-10A cells was more pronounced and was accompanied by
      elevated transcript levels of caspase 1, ERbeta2, ERbeta5, TR2 and USP2. Our data
      suggest that upregulation of genes with known growth inhibitory or apoptotic
      functions in mammary epithelial cells might contribute to the protective action
      of this adipocytokine.

PMID- 18827815
TI  - Gene expression profiling of liver metastases from colorectal cancer as potential
      basis for treatment choice.
AB  - At present no reports on gene expression profiling of liver metastases from
      colorectal cancer are available. We identified two different signatures using
      Affymetrix platform: epidermal growth factor receptor pathway was upregulated in
      metachronous lesions, whereas the pathway mainly related to angiogenesis was in
      synchronous lesions. Synchronous or metachronous liver metastases could be
      treated differently on the basis of different molecular pathways.

PMID- 18827816
TI  - Integrative approach for differentially overexpressed genes in gastric cancer by
      combining large-scale gene expression profiling and network analysis.
AB  - Gene expression profiling is a valuable tool for identifying differentially
      expressed genes in studies of disease subtype and patient outcome for various
      cancers. However, it remains difficult to assign biological significance to the
      vast number of genes. There is an increasing awareness of gene expression profile
      as an important part of the contextual molecular network at play in complex
      biological processes such as cancer initiation and progression. This study
      analysed the transcriptional profiles commonly activated at different stages of
      gastric cancers using an integrated approach combining gene expression profiling
      of 222 human tissues and gene regulatory dynamic mapping. We focused on an
      inferred core network with CDKN1A (p21(WAF1/CIP1)) as the hub, and extracted
      seven candidates for gastric carcinogenesis (MMP7, SPARC, SOD2, INHBA, IGFBP7,
      NEK6, LUM). They were classified into two groups based on the correlation between
      expression level and stage. The seven genes were commonly activated and their
      expression levels tended to increase as disease progressed. NEK6 and INHBA are
      particularly promising candidate genes overexpressed at the protein level, as
      confirmed by immunohistochemistry and western blotting. This integrated approach
      could help to identify candidate players in gastric carcinogenesis and
      progression. These genes are potential markers of gastric cancer regardless of
      stage.

PMID- 18827817
TI  - Infections in early life and childhood leukaemia risk: a UK case-control study of
      general practitioner records.
AB  - We investigated infections in early life (diagnosed in general practice) and
      subsequent risk of childhood leukaemia in the UK General Practice Research
      Database (GPRD). All children born at GPRD practices and subsequently diagnosed
      with leukaemia were identified as cases and were individually matched (on year of
      birth, sex and practice) to up to 20 controls. The final analysis included 162
      leukaemia cases and 2215 matched controls. Conditional logistic regression
      demonstrated no evidence that children with one or more recorded infection in the
      first year of life had a reduced risk of leukaemia (OR=1.05, 95%CI 0.69, 1.59;
      P=0.83) or acute lymphoblastic leukaemia (ALL; OR=1.05, 95%CI 0.64-1.74; P=0.84).
      Our study provides no support for the Greaves hypothesis, which proposes that
      reduced or delayed exposure to infections in early life increases the risk of
      childhood ALL.

PMID- 18827818
TI  - NET1-mediated RhoA activation facilitates lysophosphatidic acid-induced cell
      migration and invasion in gastric cancer.
AB  - The most lethal aspects of gastric adenocarcinoma (GA) are its invasive and
      metastatic properties. This aggressive phenotype remains poorly understood. We
      have recently identified neuroepithelial cell transforming gene 1 (NET1), a
      guanine exchange factor (GEF), as a novel GA-associated gene. Neuroepithelial
      cell transforming gene 1 expression is enhanced in GA and it is of functional
      importance in cell invasion. In this study, we demonstrate the activity of NET1
      in driving cytoskeletal rearrangement, a key pathological mechanism in gastric
      tumour cell migration and invasion. Neuroepithelial cell transforming gene 1
      expression was increased 10-fold in response to treatment with lysophosphatidic
      acid (LPA), resulting in an increase in active levels of RhoA and a 2-fold
      increase in cell invasion. Lysophosphatidic acid-induced cell invasion and
      migration were significantly inhibited using either NET1 siRNA or a RhoA
      inhibitor (C3 exoenzyme), thus indicating the activity of both NET1 and RhoA in
      gastric cancer progression. Furthermore, LPA-induced invasion and migration were
      also significantly reduced in the presence of cytochalasin D, an inhibitor of
      cytoskeletal rearrangements. Neuroepithelial cell transforming gene 1 knockdown
      resulted in AGS cell rounding and a loss of actin filament organisation,
      demonstrating the function of NET1 in actin organisation. These data highlight
      the importance of NET1 as a driver of tumour cell invasion, an activity mediated
      by RhoA activation and cytoskeletal reorganisation.

PMID- 18827819
TI  - TGF-beta1 genotype and phenotype in breast cancer and their associations with
      IGFs and patient survival.
AB  - Transforming growth factor-beta (TGF-beta)-mediated signals play complicated
      roles in the development and progression of breast tumour. The purposes of this
      study were to analyse the genotype of TGF-beta1 at T29C and TGF-beta1 phenotype
      in breast tumours, and to evaluate their associations with IGFs and clinical
      characteristics of breast cancer. Fresh tumour samples were collected from 348
      breast cancer patients. TGF-beta1 genotype and phenotype were analysed with
      TaqMan and ELISA, respectively. Members of the IGF family in tumour tissue were
      measured with ELISA. Cox proportional hazards regression analysis was performed
      to assess the association of TGF-beta1 and disease outcomes. Patients with the
      T/T (29%) genotype at T29C had the highest TGF-beta1, 707.9 pg mg(-1), followed
      by the T/C (49%), 657.8 pg mg(-1), and C/C (22%) genotypes, 640.8 pg mg(-1),
      (P=0.210, T/T vs C/C and C/T). TGF-beta1 concentrations were positively
      correlated with levels of oestrogen receptor, IGF-I, IGF-II and IGFBP-3. Survival
      analysis showed TGF-beta1 associated with disease progression, but the
      association differed by disease stage. For early-stage disease, patients with the
      T/T genotype or high TGF-beta1 had shorter overall survival compared to those
      without T/T or with low TGF-beta1; the hazard ratios (HR) were 3.54 (95% CI: 1.21
      10.40) for genotype and 2.54 (95% CI: 1.10-5.89) for phenotype after adjusting
      for age, grade, histotype and receptor status. For late-stage disease, however,
      the association was different. The T/T genotype was associated with lower risk of
      disease recurrence (HR=0.13, 95% CI: 0.02-1.00), whereas no association was found
      between TGF-beta1 phenotype and survival outcomes. The study suggests a complex
      role of TGF-beta1 in breast cancer progression, which supports the finding of in
      vitro studies that TGF-beta1 has conflicting effects on tumour growth and
      metastasis.

PMID- 18827820
TI  - Identification of novel neuroendocrine-specific tumour genes.
AB  - Neuroendocrine tumours (NETs) comprise a heterogenous group of malignancies with
      an often unpredictable course, and with limited treatment options. Thus, new
      diagnostic, prognostic, and therapeutic markers are needed. To shed new lights
      into the biology of NETs, we have by cDNA transcript profiling, sought to
      identify genes that are either up- or downregulated in NE as compared with non-NE
      tumour cells. A panel of six NET and four non-NET cell lines were examined, and
      out of 12 743 genes examined, we studied in detail the 200 most significantly
      differentially expressed genes in the comparison. In addition to potential new
      diagnostic markers (NEFM, CLDN4, PEROX2), the results point to genes that may be
      involved in the tumorigenesis (BEX1, TMEPAI, FOSL1, RAB32), and in the processes
      of invasion, progression and metastasis (MME, STAT3, DCBLD2) of NETs.
      Verification by real time qRT-PCR showed a high degree of consistency to the
      microarray results. Furthermore, the protein expression of some of the genes were
      examined. The results of our study has opened a window to new areas of research,
      by uncovering new candidate genes and proteins to be further investigated in the
      search for new prognostic, predictive, and therapeutic markers in NETs.

PMID- 18827821
TI  - Faecal tumour pyruvate kinase M2: not a good marker for the detection of
      colorectal adenomas.

PMID- 18827822
TI  - Mammographic screening for young women with a family history of breast cancer:
      knowledge and views of those at risk.
AB  - Although the effectiveness of mammography for women under the age of 50 years
      with a family history of breast cancer (FHBC) has not yet been proven, annual
      screening is being offered to these women to manage breast cancer risk. This
      study investigates women's awareness and interpretation of their familial risk
      and knowledge and views about mammographic screening. A total of 2231 women from
      21 familial/breast/genetics centres who were assessed as moderate risk (17-30%
      lifetime risk) or high risk (>30% lifetime risk) completed a questionnaire before
      their mammographic screening appointment. Most women (70%) believed they were
      likely, very likely or definitely going to develop breast cancer in their
      lifetime. Almost all women (97%) understood that the purpose of mammographic
      screening was to allow the early detection of breast cancer. However, 20%
      believed that a normal mammogram result meant there was definitely no breast
      cancer present, and only 4% understood that screening has not been proven to save
      lives in women under the age of 50 years. Women held positive views on
      mammography but did not appear to be well informed about the potential
      disadvantages. These findings suggest that further attention should be paid to
      improving information provision to women with an FHBC being offered routine
      screening.

PMID- 18827825
TI  - Re: 'Population mixing, socio-economic status and incidence of childhood acute
      lymphoblastic leukaemia in England and Wales--analysis by census ward' and
      'Childhood leukaemia and population movements in France, 1990-2003'.

PMID- 18827826
TI  - The IL-33/ST2 pathway: therapeutic target and novel biomarker.
AB  - For many years, the interleukin-1 receptor family member ST2 was an orphan
      receptor that was studied in the context of inflammatory and autoimmune disease.
      However, in 2005, a new cytokine--interleukin-33 (IL-33)--was identified as a
      functional ligand for ST2. IL-33/ST2 signalling is involved in T-cell mediated
      immune responses, but more recently, an unanticipated role in cardiovascular
      disease has been demonstrated. IL-33/ST2 not only represents a promising
      cardiovascular biomarker but also a novel mechanism of intramyocardial fibroblast
      cardiomyocyte communication that may prove to be a therapeutic target for the
      prevention of heart failure.

PMID- 18827827
TI  - Sirtuins--novel therapeutic targets to treat age-associated diseases.
AB  - Sirtuins post-translationally modulate the function of many cellular proteins
      that undergo reversible acetylation-deacetylation cycles, affecting physiological
      responses that have implications for treating diseases of ageing. Potent small
      molecule modulators of sirtuins have shown efficacy in preclinical models of
      metabolic, neurodegenerative and inflammatory diseases, and so hold promise for
      drug discovery efforts in multiple therapeutic areas. Here, we discuss current
      knowledge and data that strengthens sirtuins as a druggable set of enzymes for
      the treatment of age-associated diseases, including activation of SIRT1 in type 2
      diabetes.

PMID- 18827828
TI  - Therapeutic application of histone deacetylase inhibitors for central nervous
      system disorders.
AB  - Histone deacetylases (HDACs)--enzymes that affect the acetylation status of
      histones and other important cellular proteins--have been recognized as
      potentially useful therapeutic targets for a broad range of human disorders.
      Pharmacological manipulations using small-molecule HDAC inhibitors--which may
      restore transcriptional balance to neurons, modulate cytoskeletal function,
      affect immune responses and enhance protein degradation pathways--have been
      beneficial in various experimental models of brain diseases. Although mounting
      data predict a therapeutic benefit for HDAC-based therapy, drug discovery and
      development of clinical candidates face significant challenges. Here, we
      summarize the current state of development of HDAC therapeutics and their
      application for the treatment of human brain disorders such as Rubinstein-Taybi
      syndrome, Rett syndrome, Friedreich's ataxia, Huntington's disease and multiple
      sclerosis.

PMID- 18827829
TI  - C1q: the perfect complement for a synaptic feast?
AB  - The efficient and selective removal of apoptotic cells is an important feature of
      tissue development, homeostasis and pathology. In the nervous system, synapses
      and distal axons are selectively eliminated as part of the remodelling that
      underpins development and pathology, through a process that has some features in
      common with apoptotic cell removal. Components of the complement cascade are
      implicated in the efficient removal of apoptotic cells outside the nervous
      system, and recent evidence suggests that the complement components C1q and C3
      have a role in the selective tagging of supernumerary synapses in the developing
      visual system and in their efficient removal by as yet unidentified cells.

PMID- 18827830
TI  - The ethics of phase I trials of biologic agents.

PMID- 18827831
TI  - Magnetic resonance imaging assessment of regional cerebral blood flow after
      asphyxial cardiac arrest in immature rats.
AB  - Cerebral blood flow (CBF) alterations after asphyxial cardiac arrest (CA) are not
      defined in developmental animal models or humans. We characterized regional and
      temporal changes in CBF from 5 to 150 mins after asphyxial CA of increasing
      duration (8.5, 9, 12 min) in postnatal day (PND) 17 rats using the noninvasive
      method of arterial spin-labeled magnetic resonance imaging (ASL-MRI). We also
      assessed blood-brain barrier (BBB) permeability, and evaluated the relationship
      between CBF and mean arterial pressure after resuscitation. After all durations
      of asphyxia CBF alterations were region dependent. After 8.5- and 9-min asphyxia,
      intense subcortical hyperemia at 5 min was followed by return of CBF to baseline
      values by 10 mins. After 12-min asphyxia, hyperemia was absent and hypoperfusion
      reached a nadir of 38% to 65% of baselines with the lowest values in the cortex.
      BBB was impermeable to gadoteridol 150 mins after CA. CBF in the 12-min CA group
      was blood pressure passive at 60 min assessed via infusion of epinephrine. ASL
      MRI assessment of CBF after asphyxial CA in PND 17 rats reveals marked duration
      and region-specific reperfusion patterns and identifies possible new therapeutic
      targets.

PMID- 18827832
TI  - Induction of the Wnt antagonist, Dickkopf-1, contributes to the development of
      neuronal death in models of brain focal ischemia.
AB  - Inhibition of the canonical Wnt pathway has been implicated in the
      pathophysiology of neuronal death. Here, we report that the secreted Wnt
      antagonist, Dickkopf-1 (Dkk-1) is rapidly induced in neurons after induction of
      focal brain ischemia. In rats undergoing transient focal ischemia in response to
      brain infusion of endothelin-1, Dkk-1 was induced in neurons of the ischemic core
      and the penumbra region. Induction of Dkk-1 was associated with a reduced
      expression of beta-catenin (a downstream signaling molecule of the canonical Wnt
      pathway), and was not observed in neurons expressing the protective protein, heat
      shock protein-70. Treatment with lithium ions, which, inter alia, rescue the
      canonical Wnt pathway, was highly protective against ischemic damage. Dkk-1 was
      also induced in cortical neurons of mice undergoing permanent middle cerebral
      artery (MCA) occlusion. This model allowed us to compare wild-type mice with
      doubleridge mice, which are characterized by a reduced expression of Dkk-1.
      Doubleridge mice showed an attenuated reduction of beta-catenin and a reduced
      infarct volume in response to MCA occlusion, providing a direct demonstration
      that Dkk-1 contributes to the pathophysiology of ischemic neuronal damage. These
      data rise the interesting possibility that Dkk-1 antagonists or drugs that rescue
      the Wnt pathway might be neuroprotective in stroke.

PMID- 18827833
TI  - Intracerebral hemorrhage leads to infiltration of several leukocyte populations
      with concomitant pathophysiological changes.
AB  - Intracerebral hemorrhage (ICH) is a stroke subtype with high rates of mortality
      and morbidity. The immune system, particularly complement and cytokine signaling,
      has been implicated in brain injury after ICH. However, the cellular immunology
      associated with ICH has been understudied. In this report, we use flow cytometry
      to quantitatively profile immune cell populations that infiltrate the brain 1 and
      4 days post-ICH. At 1 day CD45(hi) GR-1(+) cells were increased 2.0-fold compared
      with saline controls (P<or=0.05); however, we did not observe changes in any
      other cell populations analyzed. At 4 days ICH mice presented with a 2.4-fold
      increase in CD45(hi) cells, a 1.9-fold increase in CD45(hi) GR-1(-) cells, a 3.4
      fold increase in CD45(hi) GR-1(+) cells, and most notably, a 1.7-fold increase in
      CD4(+) cells (P<or=0.05 for all groups), compared with control mice. We did not
      observe changes in the numbers of CD8(+) cells or CD45(lo) GR-1(-) cells (P=0.43
      and 0.49, respectively). Thus, we have shown the first use of flow cytometry to
      analyze leukocyte infiltration in response to ICH. Our finding of a CD4 T-cell
      infiltrate is novel and suggests a role for the adaptive immune system in the
      response to ICH.

PMID- 18827834
TI  - Quantitative assessment of water pools by T 1 rho and T 2 rho MRI in acute
      cerebral ischemia of the rat.
AB  - The rotating frame longitudinal relaxation magnetic resonance imaging (MRI)
      contrast, T(1 rho), obtained with on-resonance continuous wave (CW) spin-lock
      field is a sensitive indicator of tissue changes associated with hyperacute
      stroke. Here, the rotating frame relaxation concept was extended by acquiring
      both T(1 rho) and transverse rotating frame (T(2 rho)) MRI data using both CW and
      adiabatic hyperbolic secant (HSn; n=1, 4, or 8) pulses in a rat stroke model of
      middle cerebral artery occlusion. The results show differences in the sensitivity
      of spin-lock T(1 rho) and T(2 rho) MRI to detect hyperacute ischemia. The most
      sensitive techniques were CW-T(1 rho) and T(1 rho) using HS4 or HS8 pulses.
      Fitting a two-pool exchange model to the T(1 rho) and T(2 rho) MRI data acquired
      from the infarcting brain indicated time-dependent increase in free water
      fraction, decrease in the correlation time of water fraction associated with
      macromolecules, and increase in the exchange correlation time. These findings are
      consistent with known pathology in acute stroke, including vasogenic edema,
      destructive processes, and tissue acidification. Our results show that the
      sensitivity of the spin-lock MRI contrast in vivo can be modified using different
      spin-lock preparation blocks, and that physicochemical models of the rotating
      frame relaxation may provide insight into progression of ischemia in vivo.

PMID- 18827835
TI  - The postglacial recolonization of Northern Europe by Rana arvalis as revealed by
      microsatellite and mitochondrial DNA analyses.
AB  - The postglacial history of the moor frog (Rana arvalis) in Northern Europe was
      investigated with the aid of eight variable microsatellite loci and a 661 bp
      sequence of the mitochondrial cytochrome b gene. A division between eastern and
      western mitochondrial lineages was discovered, supporting two recolonization
      routes to Fennoscandia since the last glacial maximum. This result was
      corroborated by the microsatellite data, which revealed a contact zone between
      the two lineages in Northern Sweden. These findings add to the increasing
      evidence that an intraspecific genetic biodiversity founded on the existence of
      eastern and western clades is a common element in Fennoscandian fauna and flora.

PMID- 18827836
TI  - Robertsonian polymorphism in the common shrew (Sorex araneus L.) and selective
      advantage of heterozygotes indicated by their higher maximum metabolic rates.
AB  - Some cases of Robertsonian (Rb) polymorphism in the common shrew (Sorex araneus
      L.) are believed not to be associated with hybrid zones. One of the hypotheses
      explaining the persistence of such Rb polymorphism is that they are maintained by
      some form of selection for Rb heterozygotes. To test this hypothesis, we compared
      several parameters between homozygotes and Rb heterozygotes for the mp chromosome
      pair. We used shrews from Jurowce population in Poland, situated within the range
      of the Bialowieza race, where Rb polymorphism persists far from any known hybrid
      zone. We found no differences between the two karyotypic classes in maximum
      metabolic rate during running (forced activity). However, the Rb heterozygotes
      showed significantly higher maximum metabolic rate during swimming (forced
      activity combined with thermal stress). The levels of fluctuating asymmetry (FA)
      of homozygous and Rb heterozygous shrews were indistinguishable, indicating no
      effect of chromosomal heterozygosity on developmental stability of shrews. We
      suggest that selective advantages, such as the higher metabolic performance in
      activity combined with cold stress, may outweigh the expected negative effects of
      Rb heterozygosity upon fertility, and help to maintain huge areas of the Rb
      polymorphism in this species.

PMID- 18827837
TI  - Genetic structure of Oryza rufipogon Griff. in China.
AB  - Oryza rufipogon Griff. (common wild rice; CWR) is the ancestor of Asian
      cultivated rice (Oryza sativa L.). Investigation of the genetic structure and
      diversity of CWR in China will provide information about the origin of cultivated
      rice and the grain quality and yield. In this study, we used 36 simple sequence
      repeat (SSR) markers to assay 889 accessions, which were highly representative of
      whole germplasm in China. The analysis revealed a hierarchical genetic structure
      within CWR. First, CWR has diverged into two ecotypic populations, a south
      subtropical population (SSP) and a middle subtropical population (MSP), probably
      owing to natural selection by the different climates. The distribution of
      specific alleles and haplotypes indicated that Chinese CWR had both indica-like
      and japonica-like variations; the SSP was an indica-like type, whereas the MSP
      was more japonica-like. The SSP and MSP further diverged into five (HN, GD-GX1,
      GX2, FJ and YN) and two (JX-HuN1 and HuN2) geographical populations,
      respectively. The genetic data suggest the isolation by distance, although water
      systems also appear to play an important role in the formation of homogenous
      populations, and occasionally landscape was also involved. The population GD-GX1,
      which grew widely in Guangdong and Guangxi provinces, was the largest
      geographical population in China. It had a high level of genetic diversity (GD)
      and the closest genetic relationship with other inferred populations. The
      population HN, with the smallest SSR molecular weights and the highest level of
      GD, may be the most ancestral population.

PMID- 18827838
TI  - Inference of hazel grouse population structure using multilocus data: a landscape
      genetic approach.
AB  - In conservation and management of species it is important to make inferences
      about gene flow, dispersal and population structure. In this study, we used 613
      georeferenced tissue samples from hazel grouse (Bonasa bonasia) where each
      individual was genotyped at 12 microsatellite loci to make inference on
      population genetic structure, gene flow and dispersal in northern Sweden.
      Observed levels of genetic diversity suggest that Swedish hazel grouse do not
      suffer loss of genetic diversity compared with other grouse species. We found
      significant F(IS) (deviation from Hardy-Weinberg expectations) over the entire
      sample using jack-knifed estimators over loci, which is most likely explained by
      a Wahlund effect. With the use of spatial autocorrelation methods, we detected
      significant isolation by distance among individuals. Neighbourhood size was
      estimated in the order of 62-158 individuals corresponding to a dispersal
      distance of 950-1500 m. Using a spatial statistical model for landscape genetics
      to infer the number of populations and the spatial location of genetic
      discontinuities between these populations we found indications that Swedish hazel
      grouse are divided into a northern and a southern population. We could not find a
      sharp border between these two populations and none of the observed borders
      appeared to coincide with any potential geographical barriers.These results imply
      that gene flow appears somewhat unrestricted in the boreal taiga forests of
      northern Sweden and that the two populations of hazel grouse in Sweden may be
      explained by the post-glacial reinvasion history of the Scandinavian Peninsula.

PMID- 18827839
TI  - Genetic markers: how accurate can genetic data be?

PMID- 18827840
TI  - Brucellosis in kennels in western Canada.

PMID- 18827841
TI  - Lessons learned from the CVMA.

PMID- 18827842
TI  - An ethicist's commentary on production diseases.

PMID- 18827844
TI  - Congenital ocular anomalies in purebred and crossbred Rocky and Kentucky Mountain
      horses in Canada.
AB  - Multiple congenital ocular anomalies in purebred and crossbred Rocky and Kentucky
      Mountain horses in Canada are frequently diagnosed with biomicroscopic and
      indirect ophthalmoscopic examination. In order of frequency detected, these
      include temporal ciliary epithelial cysts; iridal hypoplasia; prominent corneas;
      focal temporal retinal degeneration related to ciliary cysts; and, rarely,
      retinal detachment. A pedigree analysis confirms a dominant mode of inheritance
      with incomplete penetrance and with a linkage to coat color.

PMID- 18827845
TI  - Diagnostic detection methods for Mycobacterium avium subsp. paratuberculosis in
      white-tailed deer.
AB  - This study compares the results and suitability of serological testing,
      microscopic examination, deoxyribonucleic acid (DNA) detection, and bacterial
      culture for detecting Mycobacterium avium subsp. paratuberculosis (Map) infection
      in asymptomatic farmed white-tailed deer (WTD) (Odocoileus virginianus). Deer
      were classified as infected if culture slants from their feces, lymph nodes, or
      ileum were positive, or if a polymerase chain reaction (PCR) assay detected Map
      DNA in any of its tissues. Deer identified as positive by agar gel
      immunodiffusion (AGID) testing or enzyme-linked immunosorbent assay (ELISA) but
      not by bacterial culture, Ziehl-Neelsen staining, or PCR assay were classified as
      suspect. Culture of tissues classified 10/16 (62.5%), histopathologic examination
      1/16 (6.3%), tissue smears 4/16 (25%), culture slant (CS)-PCR on feces 12/15
      (80%), CS-PCR on tissue 13/16 (81.3%), and direct PCR on uncultured tissues 5/16
      (31.3%) deer as infected. The ELISA classified 2/15 (13.3%) deer as positive and
      therefore suspect. The AGID test was negative for all deer. Fifteen of 16 deer
      were positive by 1 or more tests; only 1 deer was negative on all 11 assays. The
      CS-PCR gave superior results on antemortem fecal testing as well as postmortem
      tissue testing and can be recommended for improving the detection of Map in WTD
      at every stage of infection.

PMID- 18827846
TI  - Health Canada's policy on extra-label drug use in food-producing animals in
      Canada.

PMID- 18827847
TI  - Immunoglobulin A multiple myeloma with cutaneous involvement in a dog.
AB  - An 8-year-old rottweiler, diagnosed with multiple myeloma and multiple sites of
      cutaneous involvement, was treated with chemotherapy and radiation therapy. The
      diagnostic criteria for canine multiple myeloma, limitations of diagnostic
      testing for light chain proteinuria in dogs, and the role of radiation therapy in
      multiple myeloma patients is discussed.

PMID- 18827848
TI  - Canine brucellosis in a Saskatchewan kennel.
AB  - Canine brucellosis is rare in Canada. This report describes an outbreak of
      Brucella canis infection within a kennel, emphasizing diagnostic and pathologic
      findings. Gender differences are described. The progestational, nongravid uterus,
      female spleen, and prostate gland are consistent sites of bacterial isolation.

PMID- 18827849
TI  - A rare case of uterine adenomyosis in a Siamese cat.
AB  - A 12-year-old, female Siamese cat with a long-term history of megestrol acetate
      treatment for suppression of estrus was presented with vomiting and abdominal
      pain. Uterine adenomyosis was diagnosed after an ovariohysterectomy.

PMID- 18827850
TI  - Multi-systemic disease in a dog.

PMID- 18827851
TI  - Diagnostic ophthalmology. extrascleral extension of an uveal melanoma.

PMID- 18827852
TI  - Atriplatrade mark - HIV therapy in one pill.
AB  - In July 2006 Atriplatrade mark was approved by the US Food and Drug
      Administration (FDA), combining the active ingredients of one NNRTI and two
      NRTIs. Atriplatrade mark is the first "one-pill-daily" regimen licensed for the
      treatment of HIV-1 infection in patients older than 18 years. H was licensed in
      Europe in December 2007 Atriplatrade mark contains efavirenz 600 mg,
      emtricitabine 200 mg, and tenofovir disoproxil fumarate 300 mg. It therefore
      combines 3 compounds which have been widely used before and which were
      recommended for initial therapy due to their potency, tolerability, and safety
      profile. Efficacy and safety data of efavirenz, tenofovir DF, and emtricitabine
      are reviewed and compared with other antiretroviral drugs, which are used as
      initial therapy for treatment-naive patient.

PMID- 18827853
TI  - Pemetrexed as second-line therapy for advanced non-small-cell lung cancer
      (NSCLC).
AB  - NSCLC accounts for 80% of all cases of lung cancer, which is the leading cause of
      cancer mortality. The majority of NSCLC patients present with advanced,
      unresectable disease, which remains incurable. In advanced disease, chemotherapy
      with platinum (cisplatin or carboplatin) in combination with a third-generation
      cytotoxic drug (vinorelbine, gemcitabine, paclitaxel, or docetaxel) can provide a
      modest improvement in survival without impairing quality of life. In chemotherapy
      naive, advanced, non-squamous NSCLC patients, the combination of bevacizumab with
      chemotherapy was shown to produce better outcomes than chemotherapy alone.
      Response rates of 20%-40% can now be expected, with a median survival of 8-11
      months and a 1-year survival rate of 30%-40%. In second-line treatment, docetaxel
      has shown superiority to best supportive care in terms of survival and quality of
      life. A pooled analysis comparing docetaxel administered weekly versus 3-weekly
      found similar survival rates between the schedules and a non-significant
      reduction in febrile neutropenia for the weekly regimen. Pemetrexed, a
      multitargeted antifolate agent, has shown clear activity in several tumors,
      including mesothelioma and NSCLC. In a phase III trial, second-line treatment
      with pemetrexed demonstrated overall survival comparable to docetaxel, with a
      more manageable toxicity profile.

PMID- 18827854
TI  - AAS, growth hormone, and insulin abuse: psychological and neuroendocrine effects.
AB  - The nontherapeutic use of prescription medicines by individuals involved in sport
      is increasing. Anabolic-androgenic steroids (AAS) are the most widely abused
      drug. Much of our knowledge of the psychological and physiological effects of
      human growth hormone (hGH) and insulin has been learned from deficiency states.
      As a consequence of the Internet revolution, previously unobtainable and
      expensive designer drugs, particularly recombinant human growth hormone (rhGH)
      and insulin, have become freely available at ridiculously discounted prices from
      countries such as China and are being abused. These drugs have various
      physiological and psychological effects and medical personnel must become aware
      that such prescription medicine abuse appears to be used not only for performance
      and cosmetic reasons, but as a consequence of psychological pre-morbidity.

PMID- 18827855
TI  - Antiviral treatment in patients with hepatitis C virus-related cirrhosis awaiting
      liver transplantation.
AB  - End stage liver disease due to hepatitis C virus (HCV) infection is the most
      common indication for liver transplantation (LT) worldwide. Regretfully,
      infection of the graft by HCV occurs almost universally after LT, causing chronic
      hepatitis and early progression to cirrhosis in a significant proportion of
      recipients. Moreover, graft and patient survival are significantly worse in
      patients undergoing LT for HCV-related cirrhosis than in those transplanted for
      other indications. Therefore, many LT centers consider antiviral treatment with
      interferon and ribavirin the mainstay of managing recurrent HCV disease in LT
      recipients. The optimal time to start treatment is unclear. In most instances,
      treatment is initiated when histological evidence of disease recurrence, either
      at protocol or on-demand liver biopsies, is observed after LT. However, antiviral
      treatment initiated before LT is a potential option for some patients for two
      reasons: first, clearing or suppressing HCV before LT may reduce or eliminate the
      risk of recurrent hepatitis C in the transplanted liver and thereby improve
      survival; second, clearing HCV in cirrhotic patient may halt disease progression
      and avoid the need for transplantation. In this article, the results obtained by
      pre-transplant antiviral regimens administered to HCV-positive cirrhotic patients
      awaiting LT are discussed.

PMID- 18827856
TI  - The therapeutic effects of Rho-ROCK inhibitors on CNS disorders.
AB  - Rho-kinase (ROCK) is a serine/threonine kinase and one of the major downstream
      effectors of the small GTPase Rho. The Rho-ROCK pathway is involved in many
      aspects of neuronal functions including neurite outgrowth and retraction. The Rho
      ROCK pathway becomes an attractive target for the development of drugs for
      treating central nervous system (CNS) disorders, since it has been recently
      revealed that this pathway is closely related to the pathogenesis of several CNS
      disorders such as spinal cord injuries, stroke, and Alzheimer's disease (AD). In
      the adult CNS, injured axons regenerate poorly due to the presence of myelin
      associated axonal growth inhibitors such as myelin-associated glycoprotein (MAG),
      Nogo, oligodendrocyte-myelin glycoprotein (OMgp), and the recently identified
      repulsive guidance molecule (RGM). The effects of these inhibitors are reversed
      by blockade of the Rho-ROCK pathway in vitro, and the inhibition of this pathway
      promotes axonal regeneration and functional recovery in the injured CNS in vivo.
      In addition, the therapeutic effects of the Rho-ROCK inhibitors have been
      demonstrated in animal models of stroke. In this review, we summarize the
      involvement of the Rho-ROCK pathway in CNS disorders such as spinal cord
      injuries, stroke, and AD and also discuss the potential of Rho-ROCK inhibitors in
      the treatment of human CNS disorders.

PMID- 18827857
TI  - Treatment strategies in mucous membrane pemphigoid.
AB  - Mucous membrane pemphigoid (MMP) is an autoimmune blistering disorder that is
      characterized by subepithelial bullae. Various basement membrane zone components
      have been identified as targets of autoantibodies in MMP. Considerable
      variability exists in the clinical presentation of MMP. Mucous membranes that may
      be involved include the oral cavity, conjunctiva, nasopharynx, larynx, esophagus,
      genitourinary tract, and anus. A multidisciplinary approach is essential in the
      management of MMP. Early recognition of this disorder and treatment may decrease
      disease-related complications. The choice of agents for treatment of MMP is based
      upon the sites of involvement, clinical severity, and disease progression. For
      more severe disease, or with rapid progression, systemic corticosteroids are the
      agents of choice for initial treatment, combined with steroid-sparing agents for
      long-term maintenance. Due to the rarity of this disease, large controlled
      studies comparing the efficacy of various agents are lacking.

PMID- 18827858
TI  - Multiple sclerosis presented as clinically isolated syndrome: the need for early
      diagnosis and treatment.
AB  - OBJECTIVE: To aid in the timely diagnosis of patients who present with clinically
      isolated syndrome (CIS). PATIENTS AND METHODS: We studied 25 patients (18 women,
      7 men), originally presented in our clinic with a CIS suggestive of multiple
      sclerosis (MS). All patients underwent the full investigation procedure including
      routine tests, serology, cerebrospinal fluid (CSF) examinations, evoked
      potentials (EPs), and magnetic resonance imaging (MRI) of brain and cervical
      spinal cord. Patients were imaged at baseline, and every three months thereafter
      up to a year. RESULTS: The CIS was consisted of optic neuritis in 12 cases,
      incomplete transverse myelitis (ITM) in 7 cases, Lhermitte sign in 2 cases,
      internuclear ophthalmoplegia (INO) in 2 cases, mild brainstem syndrome in 1 case,
      and tonic-clonic seizures in 1 case. Using the baseline and three-month scans
      18/25 (72%) patients developed definite MS in one year of follow up while 7 (28%)
      had no further findings during this observation period. Immunomodulatory
      treatments were applied to all definite MS patients. CONCLUSION: In light of new
      treatments available, MRIs at 3 month intervals are helpful to obtain the
      definite diagnosis of MS as early as possible.

PMID- 18827859
TI  - Performance of the OptiMAL dipstick in the diagnosis of malaria infection in
      pregnancy.
AB  - The accuracy of OptiMAL((R)) dipsticks was compared with that of microscopy in
      the diagnosis of malaria infection in pregnancy. During the course of a clinical
      trial of antimalarial drugs in pregnancy, we screened 4500 pregnant women of all
      parities who accessed antenatal clinic services at St. Theresa's Hospital's in
      Nkoranza, Ghana, between March 2003 and December 2004 with OptiMAL((R)) dipsticks
      and confirmed the diagnosis of malaria with microscopy. We determined the
      sensitivity, specificity, positive and negative predictive values, and the area
      under receiver operating characteristic (ROC) curve for the OptiMAL((R)) antigen
      test compared to microscopy for the diagnosis of malaria infection in pregnancy.
      OptiMAL((R)) dipsticks had a sensitivity of 96.6%, specificity of 85.4%, a
      positive predictive value of 92.7%, a negative predictive value of 92.6%, and an
      area under the ROC curve of 0.91 (95% CI of 0.90-0.92). The diagnostic accuracy
      of the OptiMAL((R)) dipstick is high and the test may have practical use in the
      diagnosis of malaria infection in pregnancy in malaria endemic countries.

PMID- 18827860
TI  - Impact upon clinical outcomes of translation of PNA FISH-generated laboratory
      data from the clinical microbiology bench to bedside in real time.
AB  - Fluorescence in situ hybridization using peptide nucleic acid probes (PNA-FISH)
      differentiates Staphylococcus aureus from other Gram-positive-cocci in clusters
      (GPCC). 101/202 patients with GPCC+ blood cultures were randomly assigned to
      clinician-notification of PNA FISH results. Notification was associated with
      reduced mortality (8% vs.17%, p = 0.05), further antibiotic use (median -2.5
      days, p = 0.01), and trended toward reduced hospital stay and charges.

PMID- 18827861
TI  - Efficacy of deoxyspergualine for antibody-mediated rejection and proteinuria
      after kidney transplantation.
AB  - A patient showing antibody-mediated rejection (AMR) with severe vasculitis, and
      massive proteinuria after kidney transplantation was treated with
      deoxyspergualine (DSG, Spanidin((R)), Nippon Kayaku). DSG showed marked efficacy
      for this patient's symptoms. We report on a patient for whom DSG was effective
      against AMR after renal transplantation.

PMID- 18827862
TI  - Valproate-associated reversible encephalopathy in a 3-year-old girl with
      Pallister-Killian syndrome.
AB  - Valproic acid (VPA) is considered to be a drug of first choice for the therapy of
      generalized and focal epilepsies, including special epileptic syndromes. The drug
      is usually well tolerated, rare serious complications may occur in some patients,
      including hemorrhagic pancreatitis, coagulapathies, bone marrow suppression, VPA
      induced hepatotoxicity and encephalopathy. We report a case of VPA-associated
      encephalopathy without hyperammonemia in a 3-year-old girl with Pallister-Killian
      Syndrom, combined with a mild hepatopathy and thrombopathy. After withdrawal of
      VPA, the clinical symptoms and the electroencephalography-alterations vanished
      rapidly.

PMID- 18827863
TI  - An "acquired" hemoglobin J variant in a sickle cell disease patient.
AB  - We report the case of a rare hemoglobin variant, "Hemoglobin J", discovered while
      performing hemoglobin electrophoresis following exchange transfusion of a sickle
      cell disease patient. It is usual practice in our institution to confirm the
      hemoglobin S level in sickle cell disease patients after red cell exchange. The
      patient had received 5 red cell units and the source of this variant was traced
      back to two of those units. Due to the uncertain clinical impact of this variant,
      and the lack of specific guidelines, the two donors were deferred from future
      donations to our institution.

PMID- 18827864
TI  - The use of fondaparinux for the treatment of venous thromboembolism in a patient
      with heparin-induced thombocytopenia and thrombosis caused by heparin flushes.
AB  - Heparin-induced thrombocytopenia (HIT) is an immunologic drug reaction
      characterized by paradoxical association with venous and arterial thrombosis. The
      syndrome is caused by IgG antibodies that are reactive against complexes of
      platelet factor 4 and heparin. Fondparinux does not bind to platelet factor 4, is
      structurally too short to induce an antibody response, and could in theory be a
      useful agent to treat HIT. A 69-year-old white female presented with a lower
      extremity extensive iliofemoral deep vein thrombosis after a right total knee
      arthroplasty and was subsequently found to have a pulmonary embolism. The patient
      was noted to have heparin flushes during her operation. Her platelet drop
      decreased >50% from baseline during initiation of antithrombotic therapy. She was
      started on subcutaneous fondaparinux 7.5 mg once daily injection. Her serotonin
      release assay and enzyme-linked immunosorbent assay for heparin antibodies were
      positive for HIT. Her platelet count nadir was 60 x 0(3)/mm(3) on day 5 and the
      platelet count rebounded after 8 days of fondaparinux therapy. No recurrent
      thrombotic or bleeding events were noted throughout her therapy. Anecdotal
      reports have shown that fondaparinux can be a useful agent to treat HIT with or
      without thrombosis.

PMID- 18827865
TI  - Concurrent Chagas' disease and borderline disseminated cutaneous leishmaniasis:
      The role of amiodarone as an antitrypanosomatidae drug.
AB  - The occurrence of mixed infections of Trypanosoma cruzi and Leishmania spp. is
      becoming a common feature in Central and South America due to overlapping endemic
      areas. Unfortunately, the possibilities for treating flagellated kinetoplastid
      infections are still very limited and most of the available drugs exhibit severe
      side effects. Although the development of new drugs for Leishmania has markedly
      improved in the last years, the tendency is still to employ antimonial compounds.
      On the other hand, treatment for Chagas' disease is only available for the acute
      phase with no effective therapeutical options for chronic stage disease. The
      following case report substantiates the recently discovered effect of amiodarone
      as a nonconventional antiparasitic drug, particularly against Leishmania,
      breaching a new perspective in the therapeutic management of these important
      infectious parasitic diseases.

PMID- 18827866
TI  - [Not Available].

PMID- 18827867
TI  - Combination treatment in the management of type 2 diabetes: focus on vildagliptin
      and metformin as a single tablet.
AB  - Vildagliptin is a potent and selective inhibitor of dipeptidyl peptidase-IV (DPP
      4), orally active, that improves glycemic control in patients with type 2
      diabetes (T2DM) primarily by enhancing pancreatic (alpha and beta) islet
      function. Thus vildagliptin has been shown both to improve insulin secretion and
      to suppress the inappropriate glucagon secretion seen in patients with T2DM.
      Vildagliptin reduces HbA(1c) when given as monotherapy, without weight gain and
      with minimal hypoglycemia, or in combination with the most commonly prescribed
      classes of oral hypoglycemic drugs: metformin, a sulfonylurea, a
      thiazolidinedione, or insulin. Metformin, with a different mode of action not
      addressing beta-cell dysfunction, has been used for about 50 years and still
      represents the universal first line therapy of all guidelines. However, given the
      multiple pathophysiological abnormalities in T2DM and the progressive nature of
      the disease, intensification of therapy with combinations is typically required
      over time. Recent guidelines imply that patients will require pharmacologic
      combinations much earlier to attain and sustain the increasingly stringent
      glycemic targets, with careful drug selection to avoid unwanted adverse events,
      especially hypoglycemia. The combination of metformin and vildagliptin offers
      advantages when compared to currently used combinations with additive efficacy
      and complimentary mechanisms of action, since it does not increase the risk of
      hypoglycemia and does not promote weight gain. Therefore, by specifically
      combining these agents in a single tablet, there is considerable potential to
      achieve better blood glucose control and to improve compliance to therapy.

PMID- 18827871
TI  - The difference between ballistocardiography and stem cells.

PMID- 18827868
TI  - Percutaneous coronary intervention in patients with acute coronary syndrome:
      focus on bivalirudin.
AB  - Previously, indirect thrombin inhibitors such as unfractionated heparin or low
      molecular-weight heparin were used as a standard anticoagulation during
      percutaneous coronary intervention to prevent procedural thrombotic complications
      but at a risk of hemorrhagic complications. More recently, bivalirudin, a member
      of the direct thrombin inhibitor class, has been shown to have 1) predictable
      pharmacokinetics, 2) ability to inhibit free- and clot-bound thrombin, 3) no
      properties of platelet activation, 4) avoidance of heparin-induced
      thrombocytopenia, and 5) a significant reduction of bleeding without a reduction
      in thrombotic or ischemic endpoints compared to heparin and glycoprotein IIbIIIa
      inhibitors when used in patients presenting with acute coronary syndrome who are
      planned for an invasive treatment strategy.

PMID- 18827872
TI  - Rescue of arterial function by angiotensin-(1-7): towards improvement of
      endothelial function by drug-eluting stents.
AB  - PURPOSE: To explore the hypothesis that stent placement decreases dilator
      function of various arteries outside the stented segment and that angiotensin- (1
      7) improves this function, and to assess the contribution of dilator signal
      compounds. A further objective was to test the hypothesis that on-stent delivery
      of Ang-(1-7) reduces neointima formation and improves endothelial function.
      METHODS: Abdominal aortic stenting or sham operation was performed in the rat
      four weeks after stenting and treatment with intravenous saline or Ang-(1-7)
      infusion (24 mug/kg/h); vasomotor function in isolated thoracic aorta and
      brachial and iliac artery was measured in organ baths. Furthermore, Ang-(1-7)
      eluting stents were designed and placed in rat abdominal aorta. Neointima
      formation and aortic function were tested after four weeks. RESULTS: Relaxation
      of the thoracic aorta to metacholine was decreased after stenting compared with
      shams due to a decrease in nitric oxide-mediated response (67% reduction in
      maximal NO-dependent response). Ang-(1-7) restored the response mainly through
      increased prostaglandin- and possibly also endothelial-derived hyperpolarising
      factor-mediated relaxation. Relaxation in the brachial artery decreased after
      stenting (maximal response dropped by 50%), whilst contractions to phenylephrine
      increased. Ang-(1-7) normalised vasomotor function. Iliac artery function
      remained unaltered after stenting but Ang-(1-7) increased maximal relaxations by
      65%. Delivery of Ang-(1-7) by means of a drug-eluting stent improved endothelial
      function. CONCLUSION: Stenting differentially affects dilator and contractile
      function in various arterial beds. Ang-(1-7) both improves dilator function and
      normalises contractile function. Delivery of protective peptides such as Ang-(1
      7) from the stent is a new therapy option that merits further development and
      exploration. (Neth Heart J 2008;16:293-8.).

PMID- 18827873
TI  - The many faces of aggressive aortic pathology: Loeys-Dietz syndrome.
AB  - BACKGROUND: Loeys-Dietz syndrome (LDS) is a newly recognised disorder of
      connective tissue which shares overlapping features with Marfan syndrome (MFS)
      and the vascular type of Ehlers-Danlos syndrome, including aortic root dilatation
      and skin abnormalities. It is clinically classified into types 1 and 2. LDS type
      1 can be recognised by craniofacial characteristics, e.g. hypertelorism, bifid
      uvula or cleft palate, whereas these are absent in LDS type 2. It is important to
      recognise LDS because its vascular pathology is aggressive. We describe nine LDS
      patients from four families, relate their features to published cases, and
      discuss important aspects of the diagnosis and management of LDS in order to make
      clinicians aware of this new syndrome. RESULTS: Characteristics found in the
      majority of these LDS patients were aortic root dilatation, cleft palate and/or a
      bifid/abnormal uvula. CONCLUSION: Because aortic dissection and rupture in LDS
      tend to occur at a young age or at aortic root diameters not considered at risk
      in MFS, and because the vascular pathology can be seen throughout the entire
      arterial tree, patients should be carefully followed up and aggressive surgical
      treatment is mandatory. Clinicians must therefore be aware of LDS as a cause of
      aggressive aortic pathology and that its distinguishing features can sometimes be
      easily recognised. (Neth Heart J 2008;16:299-304.).

PMID- 18827874
TI  - Regenerative cell therapy and pharmacotherapeutic intervention in heart failure:
      Part 1: Cardiovascular progenitor cells, their functions and sources.
AB  - It has been postulated that bone marrow derived endothelial progenitor cells (BM
      EPCs) are essential for neovascularisation and endothelial repair and are
      involved in pharmacological treatment, and even its potential targets. There is
      no doubt that the ultimate success of angiogenic cell therapy will be determined
      by an appropriate stimulation of certain angiogenic progenitor cell
      subpopulations. Unfortunately, the biology of EPCs is still poorly understood. In
      particular, the understanding of endogenous microenvironments within the
      progenitor cell niches is critical, and will provide us with information about
      the signalling systems that supply a basis to develop rational pharmacotherapy to
      enhance the functional activity of endogenous or transplanted progenitor cells.
      The final success of clinical improvement of progenitor cell-mediated vascular
      repair and angiogenic therapy depends on a better understanding of EPC biology
      and a smart therapeutic design. In the first part of this review we first briefly
      discuss the possible involvement of progenitor cells in chronic heart failure. In
      part 2 we focus on factors that beneficially affect BMEPCs, with an emphasis on
      pharmacological molecular pathways involved in BM-EPC-induced neovascularisation.
      (Neth Heart J 2008;16:305-9.).

PMID- 18827875
TI  - Recurrent acute pulmonary oedema after aortic and mitral valve surgery due to
      trachea malacia and obstructive sleep apnoea syndrome.
AB  - In this report we describe a patient with recurrent episodes of acute pulmonary
      oedema after aortic and mitral valve surgery. The first episode of pulmonary
      oedema was caused by mitral valve dysfunction. The second episode of pulmonary
      oedema was not clearly associated with a mitral valve problem, but reoperation
      was performed in the absence of another explanation. After the third episode of
      acute pulmonary oedema occurred, the diagnosis of obstructive sleep apnoea
      syndrome (OSAS) was considered and confirmed. After starting treatment with
      continuous positive airway pressure (CPAP) during his sleep the patient had no
      further episodes of acute respiratory failure. Our case demonstrates that acute
      pulmonary oedema after cardiothoracic surgery can be caused or at least be
      precipitated by OSAS and should be suspected in patients with unexplained
      episodes of (recurrent) pulmonary oedema. (Neth Heart J 2008;16:310-2.).

PMID- 18827876
TI  - Combination of imaging modalities in a coronary artery fistula.

PMID- 18827877
TI  - Genome-wide analysis of protein-protein interactions and involvement of viral
      proteins in SARS-CoV replication.
AB  - Analyses of viral protein-protein interactions are an important step to
      understand viral protein functions and their underlying molecular mechanisms. In
      this study, we adopted a mammalian two-hybrid system to screen the genome-wide
      intraviral protein-protein interactions of SARS coronavirus (SARS-CoV) and
      therefrom revealed a number of novel interactions which could be partly confirmed
      by in vitro biochemical assays. Three pairs of the interactions identified were
      detected in both directions: non-structural protein (nsp) 10 and nsp14, nsp10 and
      nsp16, and nsp7 and nsp8. The interactions between the multifunctional nsp10 and
      nsp14 or nsp16, which are the unique proteins found in the members of Nidovirales
      with large RNA genomes including coronaviruses and toroviruses, may have
      important implication for the mechanisms of replication/transcription complex
      assembly and functions of these viruses. Using a SARS-CoV replicon expressing a
      luciferase reporter under the control of a transcription regulating sequence, it
      has been shown that several viral proteins (N, X and SUD domains of nsp3, and
      nsp12) provided in trans stimulated the replicon reporter activity, indicating
      that these proteins may regulate coronavirus replication and transcription.
      Collectively, our findings provide a basis and platform for further
      characterization of the functions and mechanisms of coronavirus proteins.

PMID- 18827878
TI  - PfRH5: a novel reticulocyte-binding family homolog of plasmodium falciparum that
      binds to the erythrocyte, and an investigation of its receptor.
AB  - Multiple interactions between parasite ligands and their receptors on the human
      erythrocyte are a condition of successful Plasmodium falciparum invasion. The
      identification and characterization of these receptors presents a major challenge
      in the effort to understand the mechanism of invasion and to develop the means to
      prevent it. We describe here a novel member of the reticulocyte-binding family
      homolog (RH) of P. falciparum, PfRH5, and show that it binds to a previously
      unrecognized receptor on the RBC. PfRH5 is expressed as a 63 kDa protein and
      localized at the apical end of the invasive merozoite. We have expressed a
      fragment of PfRH5 which contains the RBC-binding domain and exhibits the same
      pattern of interactions with the RBC as the parent protein. Attachment is
      inhibited if the target cells are exposed to high concentrations of trypsin, but
      not to lower concentrations or to chymotrypsin or neuraminidase. We have
      determined the affinity, copy number and apparent molecular mass of the receptor
      protein. Thus, we have shown that PfRH5 is a novel erythrocyte-binding ligand and
      the identification and partial characterization of the new RBC receptor may
      indicate the existence of an unrecognized P. falciparum invasion pathway.

PMID- 18827879
TI  - P38 MAP kinase signaling is required for the conversion of CD4+CD25- T cells into
      iTreg.
AB  - CD4+CD25+ regulatory T cells (Treg) are important mediators of immune tolerance.
      A subset of Treg can be generated in the periphery by TGF-beta dependent
      conversion of conventional CD4+CD25- T cells into induced Treg (iTreg). In
      chronic viral infection or malignancy, such induced iTreg, which limit the
      depletion of aberrant or infected cells, may be of pathogenic relevance. To
      identify potential targets for therapeutic intervention, we investigated the TGF
      beta signaling in Treg. In contrast to conventional CD4+ T cells, Treg exhibited
      marked activation of the p38 MAP kinase pathway. Inhibition of p38 MAP kinase
      activity prevented the TGF-beta-dependent conversion of CD4+CD25- T cells into
      Foxp3+ iTreg in vitro. Of note, the suppressive capacity of nTreg was not
      affected by inhibiting p38 MAP kinase. Our findings indicate that signaling via
      p38 MAP kinase seems to be important for the peripheral generation of iTreg; p38
      MAP kinase could thus be a therapeutic target to enhance immunity to chronic
      viral infection or cancer.

PMID- 18827880
TI  - Towards a general theory of neural computation based on prediction by single
      neurons.
AB  - Although there has been tremendous progress in understanding the mechanics of the
      nervous system, there has not been a general theory of its computational
      function. Here I present a theory that relates the established biophysical
      properties of single generic neurons to principles of Bayesian probability
      theory, reinforcement learning and efficient coding. I suggest that this theory
      addresses the general computational problem facing the nervous system. Each
      neuron is proposed to mirror the function of the whole system in learning to
      predict aspects of the world related to future reward. According to the model, a
      typical neuron receives current information about the state of the world from a
      subset of its excitatory synaptic inputs, and prior information from its other
      inputs. Prior information would be contributed by synaptic inputs representing
      distinct regions of space, and by different types of non-synaptic, voltage
      regulated channels representing distinct periods of the past. The neuron's
      membrane voltage is proposed to signal the difference between current and prior
      information ("prediction error" or "surprise"). A neuron would apply a Hebbian
      plasticity rule to select those excitatory inputs that are the most closely
      correlated with reward but are the least predictable, since unpredictable inputs
      provide the neuron with the most "new" information about future reward. To
      minimize the error in its predictions and to respond only when excitation is "new
      and surprising," the neuron selects amongst its prior information sources through
      an anti-Hebbian rule. The unique inputs of a mature neuron would therefore result
      from learning about spatial and temporal patterns in its local environment, and
      by extension, the external world. Thus the theory describes how the structure of
      the mature nervous system could reflect the structure of the external world, and
      how the complexity and intelligence of the system might develop from a population
      of undifferentiated neurons, each implementing similar learning algorithms.

PMID- 18827881
TI  - Dermal-type macrophages expressing CD209/DC-SIGN show inherent resistance to
      dengue virus growth.
AB  - BACKGROUND: An important question in dengue pathogenesis is the identity of
      immune cells involved in the control of dengue virus infection at the site of the
      mosquito bite. There is evidence that infection of immature myeloid dendritic
      cells plays a crucial role in dengue pathogenesis and that the interaction of the
      viral envelope E glycoprotein with CD209/DC-SIGN is a key element for their
      productive infection. Dermal macrophages express CD209, yet little is known about
      their role in dengue virus infection. METHODS AND FINDINGS: Here, we showed that
      dermal macrophages bound recombinant envelope E glycoprotein fused to green
      fluorescent protein. Because dermal macrophages stain for IL-10 in situ, we
      generated dermal-type macrophages from monocytes in the presence of IL-10 to
      study their infection by dengue virus. The macrophages were able to internalize
      the virus, but progeny virus production was undetectable in the infected cells.
      In addition, no IFN-alpha was produced in response to the virus. The inability of
      dengue virus to grow in the macrophages was attributable to accumulation of
      internalized virus particles into poorly-acidified phagosomes. CONCLUSIONS:
      Aborting infection by viral sequestration in early phagosomes would present a
      novel means to curb infection of enveloped virus and may constitute a prime
      defense system to prevent dengue virus spread shortly after the bite of the
      infected mosquito.

PMID- 18827882
TI  - Protective and enhancing HLA alleles, HLA-DRB1*0901 and HLA-A*24, for severe
      forms of dengue virus infection, dengue hemorrhagic fever and dengue shock
      syndrome.
AB  - BACKGROUND: Dengue virus (DV) infection is one of the most important mosquito
      borne diseases in the tropics. Recently, the severe forms, dengue hemorrhagic
      fever (DHF) and dengue shock syndrome (DSS), have become the leading cause of
      death among children in Southern Vietnam. Protective and/or pathogenic T cell
      immunity is supposed to be important in the pathogenesis of DHF and DSS.
      METHODOLOGY/PRINCIPAL FINDINGS: To identify HLA alleles controlling T cell
      immunity against dengue virus (DV), we performed a hospital-based case control
      study at Children's Hospital No.2, Ho Chi Minh City (HCMC), and Vinh Long
      Province Hospital (VL) in Southern Vietnam from 2002 to 2005. A total of 211 and
      418 patients with DHF and DSS, respectively, diagnosed according to the World
      Health Organization (WHO) criteria, were analyzed for their characteristic HLA-A,
      -B and -DRB1 alleles. Four hundred fifty healthy children (250 from HCMC and 200
      from VL) of the same Kinh ethnicity were also analyzed as population background.
      In HLA class I, frequency of the HLA-A*24 showed increased tendency in both DHF
      and DSS patients, which reproduced a previous study. The frequency of A*24 with
      histidine at codon 70 (A*2402/03/10), based on main anchor binding site
      specificity analysis in DSS and DHF patients, was significantly higher than that
      in the population background groups (HCMC 02-03 DSS: OR = 1.89, P = 0.008, DHF:
      OR = 1.75, P = 0.033; VL 02-03 DSS: OR = 1.70, P = 0.03, DHF: OR = 1.46, P =
      0.38; VL 04-05 DSS: OR = 2.09, P = 0.0075, DHF: OR = 2.02, P = 0.038). In HLA
      class II, the HLA-DRB1*0901 frequency was significantly decreased in secondary
      infection of DSS in VL 04-05 (OR = 0.35, P = 0.0025, Pc = 0.03). Moreover, the
      frequency of HLA-DRB1*0901 in particular was significantly decreased in DSS when
      compared with DHF in DEN-2 infection (P = 0.02). CONCLUSION: This study improves
      our understanding of the risk of HLA-class I for severe outcome of DV infection
      in the light of peptide anchor binding site and provides novel evidence that HLA
      class II may control disease severity (DHF to DSS) in DV infection.

PMID- 18827883
TI  - The potential impact of density dependent fecundity on the use of the faecal egg
      count reduction test for detecting drug resistance in human hookworms.
AB  - Current efforts to control human soil-transmitted helminth (STH) infections
      involve the periodic mass treatment of people, particularly children, in all
      endemic areas, using benzimidazole and imidothiazole drugs. Given the fact that
      high levels of resistance have developed to these same drugs in roundworms of
      livestock, there is a need to monitor drug efficacy in human STHs. The faecal egg
      count reduction test (FECRT), in which faecal egg output is measured pre- and
      post-drug treatment, is presently under examination by WHO as a means of
      detecting the emergence of resistance. We have examined the potential impact of
      density dependent fecundity on FECRT data. Recent evidence with the canine
      hookworm indicates that the density dependent egg production phenomenon shows
      dynamic properties in response to drug treatment. This will impact on
      measurements of drug efficacy, and hence drug resistance. It is likely that the
      female worms that survive a FECRT drug treatment in some human cases will respond
      to the relaxation of density dependent constraints on egg production by
      increasing their egg output significantly compared to their pre-treatment levels.
      These cases will therefore underestimate drug efficacy in the FECRT. The degree
      of underestimation will depend on the ability of the worms within particular
      hosts to increase their egg output, which will in turn depend on the extent to
      which their egg output is constrained prior to the drug treatment. As worms
      within different human cases will likely be present at quite different densities
      prior to a proposed FECRT, there is potential for the effects of this phenomenon
      on drug efficacy measurements to vary considerably within any group of potential
      FECRT candidates. Measurement of relative drug efficacy may be improved by
      attempting to ensure a consistent degree of underestimation in groups of people
      involved in separate FECRTs. This may be partly achieved by omission of cases
      with the heaviest infections from a FECRT, as these cases may have the greatest
      potential to increase their egg output upon removal of density dependent
      constraints. The potential impact of worm reproductive biology on the utility of
      the FECRT as a resistance detection tool highlights the need to develop new drug
      resistance monitoring methods which examine either direct drug effects on
      isolated worms with in vitro phenotypic assays, or changes in worm genotypes.

PMID- 18827885
TI  - Identification of lymphatics within the colonic lamina propria in inflammation
      and neoplasia using the monoclonal antibody D2-40.
AB  - CONTEXT: Lymphatic vessels are believed to be absent in the colon above the level
      of the mucularis mucosae. However, in our experience, lymphatic vessels are
      sometimes identifiable within the lamina propria in the setting of inflammation
      and neoplasia. OBJECTIVE: We sought to assess the presence of lymphatics within
      the colonic lamina propria in neoplastic and inflammatory conditions using the
      lymphatic endothelium-specific immunohistochemical marker D2-40. DESIGN:
      Representative sections of normal colon, inflamed colon, hyperplastic polyps,
      inflammatory polyps, adenomatous polyps, adenomatous polyps containing
      intramucosal carcinoma, and invasive colonic adenocarcinomas were subjected to
      immunohistochemical staining with D2-40. The presence of immunopositive lymphatic
      vessels was assessed. Lymphatic density within the lamina propria was calculated
      quantitatively, and the presence of inflammation was graded subjectively on a
      four-tiered scale (0-3). RESULTS: Lymphatics were not identified within the
      lamina propria of normal colon. However, lymphatics were identified within the
      lamina propria in the majority of cases with neoplasia and/or inflammation.
      Additionally, there was a non-significant trend toward higher lymphatic vessel
      density in cases with increasing inflammation. CONCLUSIONS: Lymphatic vessels are
      present within the lamina propria of colon in pathologic states, including cases
      of intramucosal carcinoma. This "aberrant" lymphangiogenesis is likely to be
      driven by inflammation and/or neoplasia.

PMID- 18827884
TI  - Schistosoma mansoni tegument protein Sm29 is able to induce a Th1-type of immune
      response and protection against parasite infection.
AB  - BACKGROUND: Schistosomiasis continues to be a significant public health problem.
      This disease affects 200 million people worldwide and almost 800 million people
      are at risk of acquiring the infection. Although vaccine development against this
      disease has experienced more failures than successes, encouraging results have
      recently been obtained using membrane-spanning protein antigens from the tegument
      of Schistosoma mansoni. Our group recently identified Sm29, another antigen that
      is present at the adult worm tegument surface. In this study, we investigated
      murine cellular immune responses to recombinant (r) Sm29 and tested this protein
      as a vaccine candidate. METHODS AND FINDINGS: We first show that Sm29 is located
      on the surface of adult worms and lung-stage schistosomula through confocal
      microscopy. Next, immunization of mice with rSm29 engendered 51%, 60% and 50%
      reduction in adult worm burdens, in intestinal eggs and in liver granuloma
      counts, respectively (p<0.05). Protective immunity in mice was associated with
      high titers of specific anti-Sm29 IgG1 and IgG2a and elevated production of IFN
      gamma, TNF-alpha and IL-12, a typical Th1 response. Gene expression analysis of
      worms recovered from rSm29 vaccinated mice relative to worms from control mice
      revealed a significant (q<0.01) down-regulation of 495 genes and up-regulation of
      only 22 genes. Among down-regulated genes, many of them encode surface antigens
      and proteins associated with immune signals, suggesting that under immune attack
      schistosomes reduce the expression of critical surface proteins. CONCLUSION: This
      study demonstrates that Sm29 surface protein is a new vaccine candidate against
      schistosomiasis and suggests that Sm29 vaccination associated with other
      protective critical surface antigens is the next logical strategy for improving
      protection.

PMID- 18827886
TI  - An unusual log-splitter injury leading to radial artery thrombosis, ulnar artery
      laceration, and scapholunate dissociation.
AB  - A log splitter is a gasoline- or diesel-powered machine that uses a hydraulic
      powered cutting wedge to do the work of an axe. Log-splitter injuries that do not
      result in amputation of digits or limbs are uncommon and not well described in
      the literature. We present a unique case of a patient who sustained a log
      splitter injury that resulted in thrombosis of the radial artery and avulsion
      laceration of the ulnar artery leading to acute hand ischemia, in addition to
      scapholunate ligament disruption leading to a DISI deformity. In this case,
      thrombolytic therapy was contraindicated and surgical revascularization was the
      best possible treatment option. Our case illustrates the pitfalls of using this
      modality in a crush injury, since the use of thrombolytics in this instance would
      have resulted in severe hemorrhage. An important clinical caveat is the
      potentially misleading arteriographic diagnosis of thrombosis and/or spasm.

PMID- 18827887
TI  - Mission impossible: the American schistosomiasis delegation's visit to China in
      1975.

PMID- 18827888
TI  - Mandatory school vaccinations: the role of tort law.

PMID- 18827889
TI  - Reflections from the global health front: introduction.

PMID- 18827890
TI  - Reflections from the global health front: a medical mission to Honduras.

PMID- 18827891
TI  - Reflections from the global health front: the whole patient.

PMID- 18827892
TI  - CD36 is significantly correlated with adipophilin in human carotid lesions and
      inversely correlated with plasma ApoAI.
AB  - OxLDL uptake and cholesterol efflux inhibition in macrophages play a key role in
      atherosclerotic plaque formation, rupture, and thrombotic ischemia. This study
      investigates genes implicated in OxLDL uptake (CD36, SRA), cholesterol efflux
      inhibition (adipophilin, ADFP), and inflammatory recruitments of leukocytes (IL
      8) in plaque lesion areas (PLAs) compared to nonplaque lesion areas (NPLAs) in
      human carotid endarterectomy specimens. Gene and protein expressions were assayed
      using quantitative PCR and quantitative immunohistochemistry. Pearson tests were
      used to investigate potential correlation between (a) different gene expressions
      and (b) gene expression and patient's plasma constituents. CD36, SRA, ADFP, and
      IL-8 were shown to be significantly more expressed in PLA compared to NPLA. In
      PLA, a significant correlation was observed between CD36, SRA, ADFP, and IL-8
      mRNA levels. Moreover, CD36 expression level was significantly inversely
      correlated to plasma marker ApoAI. The above investigated genes/proteins may play
      a key role in the maturation of atherosclerotic lesions.

PMID- 18827893
TI  - Idiopathic low-flow priapism in prepuberty: a case report and a review of
      literature.
AB  - Introduction. The incidence of priapism in adults is higher than in children.
      Although approximately 50% of all episodes of priapism are thought to be
      idiopathic, there are a number of known specific causes of this disorder. In
      adults intracavernous therapy with papaverine, phentolamine, alprostadil or
      combinations of these agents is the most common cause of ischemic priapism. In
      children the most common etiology is sickle cell anemia for low-flow priapism or
      post-traumatic high-flow priapism. We present a 13-year-old boy, not sexually
      active presented to our outpatient clinic suffering from long standing (3.5
      hours) sustained painful erection. To the best of our knowledge the idiopathic
      low-flow priapism in pre-pubertal boy was not reported before in literature. Our
      case is the first case to be reported in pre-pubertal age. Conclusion. In pre
      pubertal boys idiopathic recurrent priapism is a rare condition. In the
      literature, several empirical therapies are described. Recently, it is postulated
      that a low dose of a PDE5 inhibitor. The early conservative management is the
      best treatment option to safe the corporeal smooth muscles from irreversible
      damage.

PMID- 18827894
TI  - Promoter DNA hypermethylation and gene repression in undifferentiated Arabidopsis
      cells.
AB  - Maintaining and acquiring the pluripotent cell state in plants is critical to
      tissue regeneration and vegetative multiplication. Histone-based epigenetic
      mechanisms are important for regulating this undifferentiated state. Here we
      report the use of genetic and pharmacological experimental approaches to show
      that Arabidopsis cell suspensions and calluses specifically repress some genes as
      a result of promoter DNA hypermethylation. We found that promoters of the MAPK12,
      GSTU10 and BXL1 genes become hypermethylated in callus cells and that
      hypermethylation also affects the TTG1, GSTF5, SUVH8, fimbrin and CCD7 genes in
      cell suspensions. Promoter hypermethylation in undifferentiated cells was
      associated with histone hypoacetylation and primarily occurred at CpG sites.
      Accordingly, we found that the process specifically depends on MET1 and DRM2
      methyltransferases, as demonstrated with DNA methyltransferase mutants. Our
      results suggest that promoter DNA methylation may be another important epigenetic
      mechanism for the establishment and/or maintenance of the undifferentiated state
      in plant cells.

PMID- 18827895
TI  - A review of the effect of injected dextranomer/hyaluronic Acid copolymer volume
      on reflux correction following endoscopic injection.
AB  - The current literature suggests that multiple variables affect vesicoureteric
      reflux (VUR) resolution rates following dextranomer/hyaluronic acid copolymer
      (Dx/HA) injection. This article reviews the evidence pertaining to the effect of
      injected Dx/HA volume on success rates following endoscopic correction. Lack of
      prospective studies which use injected volume as a continuous variable coupled
      with a nonstandardized injection technique and endpoint hinders the ability to
      reach a definite conclusion.

PMID- 18827896
TI  - Antibiotic prophylaxis in the management of vesicoureteral reflux.
AB  - Antibiotic prophylaxis has been, since 1960s, one of the management options in
      treating vesicoureteral reflux. The purpose of this review article is to provide
      a concise overview of the rational for antiobiotic prophylaxis and to discuss the
      various agents used. Some of the current controversies regarding use of
      antibiotics for reflux will also be presented.

PMID- 18827897
TI  - Practice induces function-specific changes in brain activity.
AB  - BACKGROUND: Practice can have a profound effect on performance and brain
      activity, especially if a task can be automated. Tasks that allow for
      automatization typically involve repeated encoding of information that is paired
      with a constant response. Much remains unknown about the effects of practice on
      encoding and response selection in an automated task. METHODOLOGY: To investigate
      function-specific effects of automatization we employed a variant of a Sternberg
      task with optimized separation of activity associated with encoding and response
      selection by means of m-sequences. This optimized randomized event-related design
      allows for model free measurement of BOLD signals over the course of practice.
      Brain activity was measured at six consecutive runs of practice and compared to
      brain activity in a novel task. PRINCIPAL FINDINGS: Prompt reductions were found
      in the entire cortical network involved in encoding after a single run of
      practice. Changes in the network associated with response selection were less
      robust and were present only after the third run of practice.
      CONCLUSIONS/SIGNIFICANCE: This study shows that automatization causes
      heterogeneous decreases in brain activity across functional regions that do not
      strictly track performance improvement. This suggests that cognitive performance
      is supported by a dynamic allocation of multiple resources in a distributed
      network. Our findings may bear importance in understanding the role of
      automatization in complex cognitive performance, as increased encoding efficiency
      in early stages of practice possibly increases the capacity to otherwise
      interfering information.

PMID- 18827901
TI  - Treprostinil for pulmonary hypertension.
AB  - Treprostinil is a stable, long-acting prostacyclin analogue which can be
      administered as a continuous subcutaneous infusion using a portable miniature
      delivery system. Subcutaneous treprostinil has been shown in a large multicenter
      randomized controlled trial to improve exercise capacity, clinical state,
      functional class, pulmonary hemodynamics, and quality of life in patients with
      pulmonary arterial hypertension, an uncommon disease of poor prognosis. Side
      effects include facial flush, headache, jaw pain, abdominal cramping, and
      diarrhea, all typical of prostacyclin, and manageable by symptom-directed dose
      adjustments, and infusion site pain which may make further treatment impossible
      in 7%-10% of the patients. Long-term survival in pulmonary arterial hypertension
      patients treated with subcutaneous treprostinil is similar to that reported with
      intravenous epoprostenol. There are uncontrolled data suggesting efficacy of
      subcutaneous treprostinil in chronic thromboembolic pulmonary hypertension.
      Treprostinil can also be administered intravenously, although increased doses, up
      to 2-3 times those given subcutaneously, appear to be needed to obtain the same
      efficacy. Preliminary results of a randomized controlled trial of inhaled
      treprostinil on top of bosentan and sildenafil therapies have shown significance
      on the primary endpoint, which was exercise capacity as assessed by the distance
      walked in 6 minutes. Trials of oral formulations of treprostinil have been
      initiated.

PMID- 18827902
TI  - Relaxin as a natural agent for vascular health.
AB  - Hypertension, atherothrombosis, myocardial infarction, stroke, peripheral
      vascular disease, and renal failure are the main manifestations of cardiovascular
      disease (CVD), the leading cause of death and disability in developed countries.
      Continuing insight into the pathophysiology of CVD can allow identification of
      effective therapeutic strategies to reduce the occurrence of death and/or severe
      disabilities. In this context, a healthy endothelium is deemed crucial to proper
      functioning and maintenance of anatomical integrity of the vascular system in
      many organs. Of note, epidemiologic studies indicate that the incidence of CVD in
      women is very low until menopause and increases sharply thereafter. The loss of
      protection against CVD in post-menopausal women has been chiefly attributed to
      ovarian steroid deficiency. However, besides steroids, the ovary also produces
      the peptide hormone relaxin (RLX), which provides potent vasoactive effects which
      render it the most likely candidate as the elusive physiological shield against
      CVD in fertile women. In particular, RLX has a specific relaxant effect on
      peripheral and coronary vasculature, exerted by the stimulation of endogenous
      nitric oxide (NO) generation by cells of the vascular wall, and can induce
      angiogenesis. Moreover, RLX inhibits the activation of inflammatory leukocytes
      and platelets, which play a key role in CVD. Experimental studies performed in
      vascular and blood cell in vitro and in animal models of vascular dysfunction, as
      well as pioneer clinical observations, have provided evidence that RLX can
      prevent and/or improve CVD, thus offering background to clinical trials aimed at
      exploring the broad therapeutic potential of human recombinant RLX as a new
      cardiovascular drug.

PMID- 18827903
TI  - Relative safety profiles of high dose statin regimens.
AB  - Recent clinical trials recommend achieving a low-density lipoprotein cholesterol
      level of <100 mg/dl in high-risk and <70 mg/dl in very high risk patients. To
      attain these goals, however, many patients will need statins at high doses. The
      most frequent side effects related to the use of statins, myopathy,
      rhabdomyolysis, and increased levels of transaminases, are unusual. Although low
      and moderate doses show a favourable profile, there is concern about the
      tolerability of higher doses. During recent years, numerous trials to analyze the
      efficacy and tolerability of high doses of statins have been published. This
      paper updates the published data on the safety of statins at high doses.

PMID- 18827904
TI  - Systematic review of implementation strategies for risk tables in the prevention
      of cardiovascular diseases.
AB  - BACKGROUND: Cardiovascular disease prevention is guided by so-called risk tables
      for calculating individual's risk numbers. However, they are not widely used in
      routine practice and it is important to understand the conditions for their use.
      OBJECTIVES: Systematic review of the literature on professionals' performance
      regarding cardiovascular risk tables, in order to develop effective
      implementation strategies. SELECTION CRITERIA: Studies were eligible for
      inclusion if they reported quantitative empirical data on the effect of
      professional, financial, organizational or regulatory strategies on the
      implementation of cardiovascular risk tables. Participants were physicians or
      nurses. OUTCOME MEASURE: Primary: professionals' self-reported performance
      related to actual use of cardiovascular risk tables. Secondary: patients'
      cardiovascular risk reduction. DATA COLLECTION AND ANALYSIS: An extensive
      strategy was used to search MEDLINE, EMBASE, CINAHL, and PSYCHINFO from database
      inception to February 2007. MAIN RESULTS: The review included 9 studies, covering
      3 types of implementation strategies (or combinations). Reported effects were
      moderate, sometimes conflicting and contradictory. Although no clear relation was
      observed between a particular type of strategy and success or failure of the
      implementation, promising strategies for patient selection and risk assessment
      seem to be teamwork, nurse led-clinics and integrated IT support. CONCLUSIONS:
      Implementation strategies for cardiovascular risk tables have been sparsely
      studied. Future research on implementation of cardiovascular risk tables needs
      better embedding in the systematic and problem-based approaches developed in
      implementation science.

PMID- 18827905
TI  - Early vascular aging (EVA): consequences and prevention.
AB  - It has often been recognized that a discrepancy exists during the clinical
      consultation between the chronological age of a patient on the one hand with the
      signs and symptoms of biological age that can be recorded on the other hand. In
      cardiovascular medicine this is obvious when a heavy smoker presents with
      features of early biological aging, for example skin appearance and impaired lung
      function. This could also be extrapolated to vascular function as the target for
      numerous cardiovascular risk factors, thereby increasing the risk of early
      cardiovascular disease (CVD). Both new and old treatment modalities can play a
      role for the prevention of early vascular aging, first of all smoking cessation
      and improved lifestyle in general, but later on also the use of drugs such as
      statins or agents that block the renin-angiotensin system (RAS). New classes of
      drugs are currently being tested for CVD prevention, including glitazones and
      rimonabant, even if adverse effects (heart failure and depression) might restrict
      their usefulness. Results from ongoing intervention studies will eventually cast
      new light on possibilities to prevent the development of vascular aging.

PMID- 18827906
TI  - Drug-eluting stents in the management of peripheral arterial disease.
AB  - Since major meta-analyses of randomized controlled trials in interventional
      cardiology showed the potential of drug-eluting stents in decreasing restenosis
      and reintervention rates after coronary artery stenting, one of the next steps in
      the treatment of arterial occlusive disease is the transfer of the active coating
      technology towards peripheral arterial interventions. In this manuscript, we aim
      to provide a literature overview on available peripheral (lower limb, renal, and
      supra-aortic) drug-eluting stent applications, debate the cost implications, and
      give recommendations for future treatment strategies.

PMID- 18827907
TI  - Combining insulins with oral antidiabetic agents: effect on hyperglycemic
      control, markers of cardiovascular risk and disease.
AB  - Patients with type 2 diabetes mellitus (T2DM) have an increased risk of
      cardiovascular disease (CVD). Unfortunately, several potential barriers exist for
      CVD risk management in diabetes, including the need for significant lifestyle
      changes, potential problems with hypoglycemia, weight gain, injection
      tolerability, treatment complexity with current diabetes therapies and other,
      unmodifiable factors. Improving glycemic control may impact CVD risk. Treatment
      of T2DM usually starts with lifestyle changes such as diet and exercise. When
      these become insufficient, pharmacotherapy is required. Various oral antidiabetic
      drugs (OADs) are available that reduce hyperglycemia. The first line of therapy
      is usually metformin, since it does not increase weight and seems to have a
      beneficial effect on CVD mortality and risk factors. As T2DM progresses, insulin
      treatment becomes necessary for the majority of patients. The last few years have
      seen the development of long-acting, rapid-acting, and premixed insulin analog
      formulations. The treat-to-target algorithms of recent studies combining OADs
      plus insulin analogs have demonstrated that patients can reach glycemic treatment
      targets with low risk of hypoglycemia, greater convenience, and--with some
      analogs--limited weight gain vs conventional insulins. These factors may possibly
      have a positive influence on CVD risk. Future studies will hopefully elucidate
      the benefits of this approach.

PMID- 18827909
TI  - The secretory phospholipase A2 group IIA: a missing link between inflammation,
      activated renin-angiotensin system, and atherogenesis?
AB  - Inflammation, lipid peroxidation and chronic activation of the renin-angiotensin
      system (RAS) are hallmarks of the development of atherosclerosis. Recent studies
      have suggested the involvement of the pro-inflammatory secretory phospholipase
      A(2) (sPLA(2))-IIA in atherogenesis. This enzyme is produced by different cell
      types through stimulation by pro-inflammatory cytokines. It is detectable in the
      intima and in media smooth muscle cells, not only in atherosclerotic lesions but
      also in the very early stages of atherogenesis. sPLA(2)-IIA can hydrolyse the
      phospholipid monolayers of low density lipoproteins (LDL). Such modified LDL show
      increased affinity to proteoglycans. The modified particles have a greater
      tendency to aggregate and an enhanced ability to insert cholesterol into cells.
      This modification may promote macrophage LDL uptake leading to the formation of
      foam cells. Furthermore, sPLA(2)-IIA is not only a mediator for localized
      inflammation but may be also used as an independent predictor of adverse outcomes
      in patients with stable coronary artery disease or acute coronary syndromes. An
      interaction between activated RAS and phospholipases has been indicated by
      observations showing that inhibitors of sPLA(2) decrease angiotensin (Ang) II
      induced macrophage lipid peroxidation. Meanwhile, various interactions between
      Ang II and oxLDL have been demonstrated suggesting a central role of sPLA(2)-IIA
      in these processes and offering a possible target for treatment. The role of
      sPLA(2)-IIA in the perpetuation of atherosclerosis appears to be the missing link
      between inflammation, activated RAS and lipid peroxidation.

PMID- 18827908
TI  - Fibrosis in diabetes complications: pathogenic mechanisms and circulating and
      urinary markers.
AB  - Diabetes mellitus is characterized by a lack of insulin causing elevated blood
      glucose, often with associated insulin resistance. Over time, especially in
      genetically susceptible individuals, such chronic hyperglycemia can cause tissue
      injury. One pathological response to tissue injury is the development of
      fibrosis, which involves predominant extracellular matrix (ECM) accumulation. The
      main factors that regulate ECM in diabetes are thought to be pro-sclerotic
      cytokines and protease/anti-protease systems. This review will examine the key
      markers and regulators of tissue fibrosis in diabetes and whether their levels in
      biological fluids may have clinical utility.

PMID- 18827910
TI  - Cardiovascular co-morbidity in rheumatic diseases.
AB  - Patients with rheumatic disorders have an increased risk of cardiovascular
      disease (CVD). This excess co-morbidity is not fully explained by traditional
      risk factors. Disease severity is a major risk factor for CVD in patients with
      rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Shared disease
      mechanisms in atherosclerosis and rheumatic disorders include immune
      dysregulation and inflammatory pathways, which are potential targets for therapy.
      Lessons from RA and SLE may have implications for future research on the
      pathogenesis of atherosclerotic vascular disease in general. Recent data indicate
      that suppression of inflammation reduces the risk of CVD morbidity and mortality
      in patients with severe RA. The modest, but clinically relevant, efficacy of
      atorvastatin treatment in RA adds to the evidence for important anti-inflammatory
      properties for statins. There is increased recognition of the need for structured
      preventive strategies to reduce the risk of CVD in patients with rheumatic
      disease. Such strategies should be based on insights into the role of
      inflammation in CVD, as well as optimal management of life style related risk
      factors. In this review, the research agenda for understanding and preventing CVD
      co-morbidity in patients with rheumatic disorders is discussed.

PMID- 18827911
TI  - Perioperative hypertension management.
AB  - Perioperative hypertension is commonly encountered in patients that undergo
      surgery. While attempts have been made to standardize the method to characterize
      the intraoperative hemodynamics, these methods still vary widely. In addition,
      there is a lack of consensus concerning treatment thresholds and appropriate
      therapeutic targets, making absolute recommendations about treatment difficult.
      Nevertheless, perioperative hypertension requires careful management. When
      treatment is necessary, therapy should be individualized for the patient. This
      paper reviews the pharmacologic agents and strategies commonly used in the
      management of perioperative hypertension.

PMID- 18827912
TI  - Pulmonary embolism in the elderly: a review on clinical, instrumental and
      laboratory presentation.
AB  - OBJECTIVE: Diagnosis of pulmonary embolism (PE) remains difficult and is often
      missed in the elderly due to nonspecific and atypical presentation. Diagnostic
      algorithms able to rule out PE and validated in young adult patients may have
      reduced applicability in elderly patients, which increases the number of
      diagnostic tools use and costs. The aim of the present study was to analyze the
      reported clinical presentation of PE in patients aged 65 and more. MATERIALS AND
      METHODS: Prospective and retrospective English language studies dealing with the
      clinical, instrumental and laboratory aspects of PE in patients more than 65 and
      published after January 1987 and indexed in MEDLINE using keywords as pulmonary
      embolism, elderly, old, venous thromboembolism (VTE) in the title, abstract or
      text, were reviewed. RESULTS: Dyspnea (range 59%-91.5%), tachypnea (46%-74%),
      tachycardia (29%-76%), and chest pain (26%-57%) represented the most common
      clinical symptoms and signs. Bed rest was the most frequent risk factor for VTE
      (15%-67%); deep vein thrombosis was detected in 15%-50% of cases. Sinus
      tachycardia, right bundle branch block, and ST-T abnormalities were the most
      frequent ECG findings. Abnormalities of chest X-ray varied (less than 50% in one
      half of the studies and more than 70% in the other one-half). Arterial blood gas
      analysis revealed severe hypoxemia and mild hypocapnia as the main findings. D
      Dimer was higher than cut-off in 100% of patients in 75% of studies. Clinical
      usefulness of D-Dimer measurement decreases with age, although the strategies
      based on D-Dimer seem to be cost-effective at least until 80 years. CONCLUSION:
      Despite limitations due to pooling data of heterogeneous studies, our review
      could contribute to the knowledge of the presentation of PE in the elderly with
      its diagnostic difficulties. A diagnostic strategy based on reviewed data is
      proposed.

PMID- 18827913
TI  - Antiplatelet drugs in cardiological practice: established strategies and new
      developments.
AB  - A common pathophysiological course in vascular diseases is an overwhelming
      activation and aggregation of blood platelets, which results in atherothrombosis.
      By causing the last decisive step of cerebral, coronary, or peripheral arterial
      ischemia thrombotic complications of atherosclerotic disease represent a major
      player in death cause statistics of most western countries. The development of
      novel therapies against platelet-dependent thrombosis and the concurrent
      improvement of existing therapeutic strategies thus is a paramount focus of
      pharmaceutical research. Currently, efficiency, dosing and indications of
      established antiplatelet substances are being re-evaluated, whilst new, so far
      unrecognized molecular targets for inhibition of platelet activity come up front.
      This not only allows for interesting new therapeutical options, but also widens
      our insight into the role platelets play in atherosclerosis in general. This
      article summarizes the relevant pathophysiology of platelet activation, presents
      current concepts in antiplatelet drug therapy, and highlights the role of
      platelets in vascular diseases apart from atherothrombosis.

PMID- 18827914
TI  - Measurement of endothelial function and its clinical utility for cardiovascular
      risk.
AB  - Over the past two decades, the central role of the endothelium in the initiation,
      progression, and clinical sequelae of atherosclerosis has been increasingly
      recognized. Assessment of the pathobiology of the endothelium and its ability to
      act as a potential therapeutic target remains an area of active research
      interest. Whilst endothelial function has been shown to be a marker for risk of
      cardiovascular events in high-risk groups, there remains considerable debate
      about the most appropriate way to assess this. We discuss the different clinical
      methods to assess endothelial function, focusing on flow-mediated dilatation
      (FMD) of the brachial artery, highlighting the importance of using a standardized
      methodology, as well as discussing the clinical limitations of using FMD in
      individuals.

PMID- 18827915
TI  - Fixed combinations in the management of hypertension: patient perspectives and
      rationale for development and utility of the olmesartan-amlodipine combination.
AB  - Although the awareness and control of hypertension has increased, only 37% of
      hypertensive patients in the US achieve the conservative goal of <140/90 mmHg.
      Achieving optimal blood pressure (BP) control is the most important single issue
      in the management of hypertension, and in most hypertensive patients, it is
      difficult or impossible to control BP with one drug. Blocking two or more BP
      regulatory systems provides a more effective and more physiologic reduction in
      BP, and current guidelines have recommended the use of combination therapy as
      first-line treatment, or early in the management of hypertension. Fixed
      combination therapy is an efficacious, relatively safe, and may be cost-effective
      method of decreasing BP in most patients with essential hypertension. Similar to
      other combinations, fixed-dose combination tablets containing the dihydropyridine
      calcium channel blocker amlodipine and the angiotensin II receptor blocker
      olmesartan bring together two distinct and complementary mechanisms of action,
      resulting in improved BP control and potential for improved target organ
      protection relative to either class of agent alone.

PMID- 18827916
TI  - Effects of early treatment with zofenopril in patients with myocardial infarction
      and metabolic syndrome: the SMILE Study.
AB  - OBJECTIVE: To evaluate the clinical efficacy of the early administration of
      zofenopril in a group of patients with and without metabolic syndrome (MS+ and MS
      ) and anterior myocardial infarction enrolled in the Survival of Myocardial
      Infarction Long-Term Evaluation (SMILE) Study. METHODS: Patients were randomized
      double-blind to zofenopril (n=719) or placebo (n=699) for 6 weeks. The primary
      end point was the effect of treatment on the 6-week combined occurrence of death
      and severe congestive heart failure. The secondary end point was the 1-year
      mortality rate. RESULTS: Of the 1418 patients included in this post-hoc analysis,
      686 (48.3%) had MS. After 6 weeks of treatment zofenopril significantly reduced
      the incidence of all-cause death and severe congestive failure (risk reduction:
      69%, 95% CI: 7-78; 2p=0.002) in MS+ patients. This was the case for 1-year
      mortality, too (29%, 95% CI: 4-41; 2p=0.048). Zofenopril was effective also in MS
      patients but the amount of relative risk reduction was less than in MS+ for both
      the primary (-11%; 2p=0.61) and secondary endpoint (-19%; 2p=0.025). CONCLUSIONS:
      Results of this post-hoc analysis of the SMILE Study demonstrate the striking
      benefit of early administration of zofenopril in MS+ patients with acute anterior
      myocardial infarction.

PMID- 18827917
TI  - Adherence with single-pill amlodipine/atorvastatin vs a two-pill regimen.
AB  - While clinical trials demonstrate the benefits of blood pressure and cholesterol
      reduction, medication adherence in clinical practice is problematic. We
      hypothesized that a single-pill would be superior to a 2-pill regimen for
      achieving adherence. In this retrospective, cohort study based on pharmacy claims
      data, patients newly initiated on a calcium channel blocker (CCB) or statin
      simultaneously or within 30 days, regardless of sequence, were followed (N=4703).
      Adherence was measured over 6 months as proportion of days covered (PDC). At
      baseline, mean age was 63.0 years, 51.6% were female, and mean number of other
      medications was 7.8. Overall, 16.9% of patients were on single-pill
      amlodipine/atorvastatin, 15.6% amlodipine + atorvastatin, 24.7% amlodipine +
      other statin, 13.9% other CCB + atorvastatin, 28.9% other CCB + other statin.
      Percentages of patients achieving adherence (PDC >or= 80%) were: 67.7%
      amlodipine/atorvastatin; 49.9% amlodipine + atorvastatin; 40.4% amlodipine +
      other statin; 46.9% other CCB + atorvastatin; 37.4% other CCB +other statin.
      After adjusting for treatment selection and cohort differences, odds ratios for
      adherence with amlodipine/atorvastatin were 1.95 (95% confidence interval [CI],
      1.80-2.13) vs amlodipine + atorvastatin, 3.10 (95% CI, 2.85-3.38) vs amlodipine +
      other statin, 2.06 (95% CI, 1.89-2.24) vs other CCB + atorvastatin, 2.85 (95% CI,
      2.61-3.10) vs other CCB + other statin (all p<0.0001). Single-pill
      amlodipine/atorvastatin may provide clinical benefits through improving
      adherence, offering clinicians a practical solution for cardiovascular risk
      management.

PMID- 18827918
TI  - The influence of polymorbidity, revascularization, and wound therapy on the
      healing of arterial ulceration.
AB  - OBJECTIVE: An ulcer categorized as Fontaine's stage IV represents a chronic
      wound, risk factor of arteriosclerosis, and co-morbidities which disturb wound
      healing. Our objective was to analyze wound healing and to assess potential
      factors affecting the healing process. METHODS: 199 patients were included in
      this 5-year study. The significance levels were determined by chi-squared and log
      rank tests. The calculation of patency rate followed the Kaplan-Meier method.
      RESULTS: Mean age and co-morbidities did not differ from those in current
      epidemiological studies. Of the patients with ulcer latency of more than 13 weeks
      (up to one year), 40% required vascular surgery. Vascular surgery was not
      possible for 53 patients and they were treated conservatively. The amputation
      rate in the conservatively treated group was 37%, whereas in the revascularizated
      group it was only 16%. Ulcers in patients with revascularization healed in 92% of
      cases after 24 weeks. In contrast, we found a healing rate of only 40% in the
      conservatively treated group (p<0.001). Revascularization appeared more often in
      diabetic patients (n=110; p<0.01) and the wound size and number of infections
      were elevated (p=0.03). Among those treated conservatively, wound healing was
      decelerated (p=0.01/0.02; chi(2) test). CONCLUSIONS: The success of
      revascularization, presence of diabetes mellitus, and wound treatment proved to
      be prognostic factors for wound healing in arterial ulcers.

PMID- 18827919
TI  - Five-year incidence of type 2 diabetes mellitus among cardiovascular disease-free
      Greek adults: findings from the ATTICA study.
AB  - OBJECTIVE: We evaluated the 5-year incidence of diabetes in an adult population
      from Greece. RESEARCH DESIGN AND METHODS: 3042 individuals (>18 years), free of
      cardiovascular disease, participated in the baseline examination (during 2001
      2002). Of this sample, 1012 men and 1035 women were found alive at the time of
      follow-up, while 32 (2.1%) men and 22 (1.4%) women died during this period. The
      rest were lost to follow-up. Incidence of type 2 diabetes mellitus was evaluated
      in 1806 participants who did not have diabetes at baseline. RESULTS: The age
      adjusted 5-year incidence of diabetes was 5.5% (men, 5.8%; women, 5.2%). A linear
      trend was observed between diabetes incidence and age (5.6% increases in
      incidence per 1-year difference in age, p<0.001). Multiple logistic regression
      analysis revealed that age (OR per 1 yr=1.04, 95% CI 1.02-1.06), waist (OR per 1
      cm=1.02, 95% CI 1.01-1.003), physical activity (OR=0.62, 95% CI 0.35-1.02) and
      family history of diabetes (OR=2.65, 95% CI 1.58-4.53), as well as fasting
      glucose levels (OR per 1 mg/dl=1.05, 95% CI 1.03-1.07), were the most significant
      baseline predictors for diabetes, after adjusting for various potential
      confounders. Additionally, presence of metabolic syndrome at baseline evaluation
      2.95-fold the risk of diabetes (95% CI 1.89-4.61), and showed better
      classification ability than the model that contained the components of the
      syndrome (ie, correct classification rate: 94.5% vs. 92.3%). CONCLUSION: Our
      findings show that a 5.5% incidence rate of diabetes within a 5-year period,
      which suggests that the prevalence of this disorder in Greece is rising. Aging,
      heredity, and metabolic syndrome were the most significant determinants of
      diabetes.

PMID- 18827920
TI  - Cigarette smoking leads to reduced relaxant responses of the cutaneous
      microcirculation.
AB  - BACKGROUND: Smoking is a major risk factor for cardiovascular disease. The
      present study was undertaken to examine if cigarette smoking translates into
      reduced relaxant responses of the peripheral microcirculation. METHODS: The
      cutaneous forearm blood flow was measured by laser Doppler flowmetry. The
      vasodilator response to the iontophorectic administration of acetylcholine (ACh),
      acting via an endothelial mechanism, and sodium nitroprusside (SNP), and acting
      via a smooth muscle mechanism were studied. The study population consisted of 17
      nonsmokers and 17 current smokers (mean age 64+/-2 years, 13 females and 4 males)
      in each matched group. RESULTS: There was no difference between the groups in
      baseline characteristics or in basal flow. Smokers showed however significantly
      reduced responses to both ACh (mean +/- SEM, from 973+/-137% in nonsmokers to
      651+/-114% in smokers, p<0.05) and SNP (from 575+/-111% in nonsmokers to 355+/
      83% in smokers, p<0.05). The response to the local heating (44 degrees C) was
      reduced in smokers (from 1188+/-215% in nonsmokers to 714+/-107% in smokers,
      p<0.01). In addition, there was no difference between men and women within the
      groups. CONCLUSIONS: The data show that cigarette smoking results in reduced
      peripheral microvascular responses to both endothelial and smooth muscle cell
      stimulation in healthy subjects, suggesting a generalized microvascular vasomotor
      function.

PMID- 18827921
TI  - Estrogen-induced improvement in coronary flow responses during atrial pacing in
      relation to endothelin-1 levels in postmenopausal women without coronary disease.
AB  - BACKGROUND: The cardioprotective role of hormonal replacement therapy remains in
      doubt, but interest is increasing in the vascular effects of estrogens especially
      in coronary circulation. METHODS: Coronary blood flow (CBF) was measured in 24
      postmenopausal women (age 55+/-3 years), whose coronary arteries appeared
      angiographically normal, during incremental atrial pacing (AP) before and 20
      minutes after intracoronary administration of either 75 ng/mL 17-beta estradiol
      (treated group, n=18) or 0.9% saline (controls, n=6). RESULTS: Before estrogen,
      no differences in the coronary vasomotor responses at AP between the two groups
      (p=NS) could be detected. After estrogen, in the treated group, at the peak of
      the second AP, the coronary artery diameter decreased by 0.17 mm (p<0.005) while
      the CBF increased by 61 mL/min (p<0.05). These changes differed significantly
      from those observed at the peak of first AP (p<0.001 for both cases). In
      contrast, in the control group no such changes were observed. The endothelin-1
      (ET-1) levels in the coronary sinus were significantly reduced after estrogen
      infusion, which was negatively correlated with the degree of coronary artery
      constriction (r= -0.40, p=0.03) and positively correlated with the increase in
      CBF (r=0.54, p=0.01). CONCLUSIONS: In postmenopausal women without coronary
      artery disease, the intracoronary estrogen infusion mediates a greater increase
      in CBF and is positively correlated with the reduction of the coronary sinus ET-1
      levels at the peak of AP.

PMID- 18827922
TI  - Early seizures in patients with acute stroke: frequency, predictive factors, and
      effect on clinical outcome.
AB  - BACKGROUND: Early seizure (ES) may complicate the clinical course of patients
      with acute stroke. The aim of this study was to assess the rate of and the
      predictive factors for ES as well the effects of ES on the clinical outcome at
      hospital discharge in patients with first-ever stroke. PATIENTS AND METHODS: A
      total of 638 consecutive patients with first-ever stroke (543 ischemic, 95
      hemorrhagic), admitted to our Stroke Unit, were included in this prospective
      study. ES were defined as seizures occurring within 7 days from acute stroke.
      Patients with history of epilepsy were excluded. RESULTS: Thirty-one patients
      (4.8%) had ES. Seizures were significantly more common in patients with cortical
      involvement, severe and large stroke, and in patient with cortical hemorrhagic
      transformation of ischemic stroke. ES was not associated with an increase in
      adverse outcome (mortality and disability). After multivariate analysis,
      hemorrhagic transformation resulted as an independent predictive factor for ES
      (OR=6.5; 95% CI: 1.95-22.61; p=0.003). CONCLUSION: ES occur in about 5% of
      patients with acute stroke. In these patients hemorrhagic transformation is a
      predictive factor for ES. ES does not seem to be associated with an adverse
      outcome at hospital discharge after acute stroke.

PMID- 18827923
TI  - Atherosclerotic lesions and mitochondria DNA deletions in brain microvessels:
      implication in the pathogenesis of Alzheimer's disease.
AB  - The pathogenesis that is primarily responsible for Alzheimer's disease (AD) and
      cerebrovascular accidents (CVA) appears to involve chronic hypoperfusion. We
      studied the ultrastructural features of vascular lesions and mitochondria in
      brain vascular wall cells from human AD biopsy samples and two transgenic mouse
      models of AD, yeast artificial chromosome (YAC) and C57B6/SJL Tg (+), which
      overexpress human amyloid beta precursor protein (AbetaPP). In situ hybridization
      using probes for normal and 5 kb deleted human and mouse mitochondrial DNA
      (mtDNA) was performed along with immunocytochemistry using antibodies against the
      Abeta peptide processed from AbetaPP, 8-hydroxy-2'-guanosine (8OHG), and
      cytochrome c oxidase (COX). More amyloid deposition, oxidative stress markers as
      well as mitochondrial DNA deletions and structural abnormalities were present in
      the vascular walls of the human AD samples and the AbetaPP-YAC and C57B6/SJL Tg
      (+) transgenic mice compared to age-matched controls. Ultrastructural damage in
      perivascular cells highly correlated with endothelial lesions in all samples.
      Therefore, pharmacological interventions, directed at correcting the chronic
      hypoperfusion state, may change the natural course of the development of
      dementing neurodegeneration.

PMID- 18827924
TI  - Intertester reliability of brachial artery flow-mediated vasodilation using upper
      and lower arm occlusion in healthy subjects.
AB  - The assessment of endothelial function as brachial artery flow-mediated
      vasodilatation is a widely used technique that determines the effect of risk
      factor intervention and may have the potential to predict the clinical benefit of
      antiatherogenic therapy. Previous studies suggest that flow-mediated dilation is
      greater using the upper-arm occlusion technique, but no data are available to
      compare intertester reliability between technicians. This study was undertaken to
      compare the amount of hyperemia between upper and lower occlusion techniques and
      to determine reproducibility between testers. Nineteen healthy adults, ages 25 to
      50, were included in the study. Brachial artery vasodilatation was measured 1 and
      3 minutes post cuff deflation and was compared with the baseline and expressed as
      a percent change. There was a tester effect in the percent change in diameter
      across all measurements. The results of this study reveal inconsistencies between
      testers when using a blood pressure cuff to induce hyperemia for the assessment
      of endothelial function through brachial artery flow-mediated vasodilation.
      However, upper arm as compared to lower arm blood pressure cuff occlusion results
      in significantly greater hyperemia and vasodilatation, even though there was a
      difference in measurements between testers.

PMID- 18827925
TI  - Diagnosis with ECG-gated MDCT of floating thrombus in aortic arch in a patient
      with type-A dissection.
AB  - Multidetector computed tomography has been shown to be accurate in noninvasive
      assessment of chest vascular disease. The motion artifacts of the thoracic aorta
      and the supra-aortic vessels were significantly reduced in the electrocardiogram
      (ECG)-gated data acquisition. This positive effect of ECG synchronization is more
      pronounced in the region of the ascending aorta, aortic arch, and proximal
      descending aorta.

PMID- 18827927
TI  - Social modulation during songbird courtship potentiates midbrain dopaminergic
      neurons.
AB  - Synaptic transmission onto dopaminergic neurons of the mammalian ventral
      tegmental area (VTA) can be potentiated by acute or chronic exposure to addictive
      drugs. Because rewarding behavior, such as social affiliation, can activate the
      same neural circuitry as addictive drugs, we tested whether the intense social
      interaction of songbird courtship may also potentiate VTA synaptic function. We
      recorded glutamatergic synaptic currents from VTA of male zebra finches who had
      experienced distinct social and behavioral conditions during the previous hour.
      The level of synaptic transmission to VTA neurons, as assayed by the ratio of
      alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) to N-methyl-D
      aspartic acid (NMDA) glutamate receptor mediated synaptic currents, was increased
      after males sang to females, and also after they saw females without singing, but
      not after they sang while alone. Potentiation after female exposure alone did not
      appear to result from stress, as it was not blocked by inhibition of
      glucocorticoid receptors. This potentiation was restricted to synapses of
      dopaminergic projection neurons, and appeared to be expressed postsynaptically.
      This study supports a model in which VTA dopaminergic neurons are more strongly
      activated during singing used for courtship than during non-courtship singing,
      and thus can provide social context-dependent modulation to forebrain areas. More
      generally, these results demonstrate that an intense social encounter can trigger
      the same pathways of neuronal plasticity as addictive drugs.

PMID- 18827928
TI  - Dynamics of alliance formation and the egalitarian revolution.
AB  - BACKGROUND: Arguably the most influential force in human history is the formation
      of social coalitions and alliances (i.e., long-lasting coalitions) and their
      impact on individual power. Understanding the dynamics of alliance formation and
      its consequences for biological, social, and cultural evolution is a formidable
      theoretical challenge. In most great ape species, coalitions occur at individual
      and group levels and among both kin and non-kin. Nonetheless, ape societies
      remain essentially hierarchical, and coalitions rarely weaken social inequality.
      In contrast, human hunter-gatherers show a remarkable tendency to egalitarianism,
      and human coalitions and alliances occur not only among individuals and groups,
      but also among groups of groups. These observations suggest that the evolutionary
      dynamics of human coalitions can only be understood in the context of social
      networks and cognitive evolution. METHODOLOGY/PRINCIPAL FINDINGS: Here, we
      develop a stochastic model describing the emergence of networks of allies
      resulting from within-group competition for status or mates between individuals
      utilizing dyadic information. The model shows that alliances often emerge in a
      phase transition-like fashion if the group size, awareness, aggressiveness, and
      persuasiveness of individuals are large and the decay rate of individual
      affinities is small. With cultural inheritance of social networks, a single
      leveling alliance including all group members can emerge in several generations.
      CONCLUSIONS/SIGNIFICANCE: We propose a simple and flexible theoretical approach
      for studying the dynamics of alliance emergence applicable where game-theoretic
      methods are not practical. Our approach is both scalable and expandable. It is
      scalable in that it can be generalized to larger groups, or groups of groups. It
      is expandable in that it allows for inclusion of additional factors such as
      behavioral, genetic, social, and cultural features. Our results suggest that a
      rapid transition from a hierarchical society of great apes to an egalitarian
      society of hunter-gatherers (often referred to as "egalitarian revolution") could
      indeed follow an increase in human cognitive abilities. The establishment of
      stable group-wide egalitarian alliances creates conditions promoting the origin
      of cultural norms favoring the group interests over those of individuals.

PMID- 18827929
TI  - Resting regulatory CD4 T cells: a site of HIV persistence in patients on long
      term effective antiretroviral therapy.
AB  - BACKGROUND: In HIV-infected patients on long-term HAART, virus persistence in
      resting long-lived CD4 T cells is a major barrier to curing the infection. Cell
      quiescence, by favouring HIV latency, reduces the risk of recognition and cell
      destruction by cytotoxic lymphocytes. Several cell-activation-based approaches
      have been proposed to disrupt cell quiescence and then virus latency, but these
      approaches have not eradicated the virus. CD4+CD25+ regulatory T cells (Tregs)
      are a CD4+ T-cell subset with particular activation properties. We investigated
      the role of these cells in virus persistence in patients on long-term HAART.
      METHODOLOGY/PRINCIPAL FINDINGS: We found evidence of infection of resting Tregs
      (HLADR(-)CD69(-)CD25(hi)FoxP3+CD4+ T cells) purified from patients on prolonged
      HAART. HIV DNA harbouring cells appear more abundant in the Treg subset than in
      non-Tregs. The half-life of the Treg reservoir was estimated at 20 months. Since
      Tregs from patients on prolonged HAART showed hyporesponsiveness to cell
      activation and inhibition of HIV-specific cytotoxic T lymphocyte-related
      functions upon activation, therapeutics targeting cell quiescence to induce virus
      expression may not be appropriate for purging the Treg reservoir. CONCLUSIONS:
      Our results identify Tregs as a particular compartment within the latent
      reservoir that may require a specific approach for its purging.

PMID- 18827930
TI  - Geographic and genetic population differentiation of the Amazonian chocolate tree
      (Theobroma cacao L).
AB  - Numerous collecting expeditions of Theobroma cacao L. germplasm have been
      undertaken in Latin-America. However, most of this germplasm has not contributed
      to cacao improvement because its relationship to cultivated selections was poorly
      understood. Germplasm labeling errors have impeded breeding and confounded the
      interpretation of diversity analyses. To improve the understanding of the origin,
      classification, and population differentiation within the species, 1241
      accessions covering a large geographic sampling were genotyped with 106
      microsatellite markers. After discarding mislabeled samples, 10 genetic clusters,
      as opposed to the two genetic groups traditionally recognized within T. cacao,
      were found by applying Bayesian statistics. This leads us to propose a new
      classification of the cacao germplasm that will enhance its management. The
      results also provide new insights into the diversification of Amazon species in
      general, with the pattern of differentiation of the populations studied
      supporting the palaeoarches hypothesis of species diversification. The origin of
      the traditional cacao cultivars is also enlightened in this study.

PMID- 18827931
TI  - Metal complex-assisted activation of small molecules. From NO to superoxide and
      peroxides.
AB  - Transition metal centres are one of the primary targets for nitric oxide (NO),
      superoxide (O2(-)) and hydrogen peroxide (H2O2), which are small molecules
      present in a biological milieu, and of industrial and environmental interest.
      Coordination to a metal centre modulates their redox behaviour in such a way that
      they become activated for an inner-sphere oxidation or reduction, depending on
      the electronic and redox properties of a particular transition metal ion. Since
      the related redox reactions play multiple roles in physiological and
      pathophysiological processes, as well as in chemical catalysis in terms of
      synthetic applications and exhaust gas purification, the elucidation of the
      mechanisms of the elementary reaction steps behind these complex processes is of
      fundamental importance. This review concentrates on our work in this area, where
      by applying low temperature and high pressure kinetic and thermodynamic
      techniques we shed more light on the mechanisms of the particular reaction steps
      involved in the activation of NO, O2(-) and various peroxides. The studies
      include work on solvent exchange reactions that control the binding of small
      molecules to the metal centre and subsequent electron-transfer processes. We paid
      special attention to different iron and manganese complexes with heme and non
      heme ligand systems.

PMID- 18827932
TI  - Metal-catalyzed nucleophilic carbon-heteroatom (C-X) bond formation: the role of
      M-X intermediates.
AB  - Many important reactions that lead to carbon-heteroatom bond formation involve
      attack of anionic heteroatom nucleophiles, such as hydroxides, alkoxides, amides,
      thiolates and phosphides, at carbon. Related catalytic transformations are
      mediated by late transition metal complexes of these groups, which remain
      nucleophilic on metal coordination as a result of repulsive filled-filled
      interactions between the heteroatom lone pairs and metal d-orbitals and/or of
      polarization of the bonds Mdelta+-Xdelta-. This Perspective presents examples of
      catalytic nucleophilic C-X bond formation in both biological and synthetic
      systems and describes how changes in the metal, ancillary ligands and X groups
      may be used to tune nucleophilic reactivity.

PMID- 18827933
TI  - Ligand-mediated decarbonylation as an efficient synthetic method to Re(I) and
      Re(II) dicarbonyl complexes.
AB  - A novel synthetic method based on a ligand-mediated decarbonylation reaction of
      complexes of the common fac-[Re(CO)3]+ core efficiently yields Re(I) and Re(II)
      dicarbonyl species.

PMID- 18827934
TI  - The role of short-range diffusion in solvent-assisted mechanochemical synthesis
      of metal complexes.
AB  - The role of short-range diffusion in solvent-assisted mechanochemical synthesis
      is demonstrated in studies of a polymorphic transition and a ligand dissociation
      reaction involving copper(I) thiocyanate complexes.

PMID- 18827935
TI  - Functionalised cyclopentadienyl zirconium compounds as potential anticancer
      drugs.
AB  - New neutral and ionic functionalised zirconocene dichloride compounds have been
      isolated and characterised. The ionic zirconocene exhibits excellent cytotoxicity
      against a range of human tumour cell lines, which represents the first active
      anticancer zirconocene dichloride compound.

PMID- 18827936
TI  - Effect of oxygen content on the 29Si NMR, Raman spectra and oxide ion
      conductivity of the apatite series, La8+xSr2-x(SiO4)6O2+x/2.
AB  - 29Si NMR data have been recorded for the apatite series La8+xSr2-x(SiO4)6O2+x/2
      (0 < or = x < or = 1.0). For x = 0, a single NMR peak is observed at a chemical
      shift of approximately -77 ppm, while as the La : Sr ratio and hence interstitial
      oxygen content is increased, a second peak at a chemical shift of approximately 
      80 ppm is observed, which has been attributed to silicate groups neighbouring
      interstitial oxide ions. An increase in the intensity of this second peak is
      observed with increasing x, consistent with an increase in interstitial oxide ion
      content, and the data are used to estimate the level of interstitial oxide ions,
      and hence Frenkel-type disorder in these materials. The increase in second 29Si
      NMR peak intensity/interstitial oxide ion content is also shown to correlate with
      an increase in conductivity. The effect of interstitial oxygen content can also
      be studied by means of Raman spectroscopy, with a new mode at 360 cm(-1)
      appearing for samples with x > 0 in the symmetric bending mode energy region of
      the SiO4 group. The intensity of this mode increases with increasing oxygen
      content, yielding results comparable to those from the NMR studies, showing the
      complementarities of the two techniques.

PMID- 18827937
TI  - Synthesis and characterisation of mixed ligand Pt(II) and Pt(IV) oxadiazoline
      complexes.
AB  - The nitrile ligands in trans-[PtX2(PhCN)2] (X = Cl, Br, I) undergo sequential 1,3
      dipolar cycloadditions with nitrones R1R2C=N+(Me)-O(-) (R1 = H, R2 = Ph; R1 =
      CO2Et, R2 = CH2CO2Et) to selectively form the Delta4-1,2,4-oxadiazoline complexes
      trans-[PtX2(PhCN) (N=C(Ph)-O-N(Me)-CR1R2)] or trans-[PtX2(N=C(Ph)-O-N(Me)
      CR1R2)2] in high yields. The reactivity of the mixed ligand complexes trans
      [PtX2(PhCN)(N=C(Ph)-O-N(Me)-CR1R2)] towards oxidation and ligand substitution was
      studied in more detail. Oxidation with Cl2 or Br2 provides the Pt(IV) species
      trans-[PtX2Y2(PhCN)(N=C(Ph)-O-N(Me)-CH(Ph))] (X, Y = Cl, Br). The mixed halide
      complex (X = Cl, Y = Br) undergoes halide scrambling in solution to form trans
      [PtX(4-n)Yn(PhCN)(N=C(Ph)-O-N(Me)-CH(Ph))] as a statistical mixture. Ligand
      substitution in trans-[PtCl2(PhCN)(N=C(Ph)-O-N(Me)-CR1R2)] allows for selective
      replacement of the coordinated nitrile by nitrogen heterocycles such as pyridine,
      DMAP or 1-benzyl-2-methylimidazole to produce mixed ligand Pt(II) complexes of
      the type trans- [PtX2(heterocycle)(N=C(Ph)-O-N(Me)-CR1R2)]. All compounds were
      characterised by elemental analysis, mass spectrometry, IR and 1H, 13C and 195Pt
      NMR spectroscopy. Single-crystal X-ray structural analysis of (R,S)-trans
      [PtBr2(N=C(Ph)-O-N(Me)-CH(Ph))2] and trans-[PtCl2(C5H5N)(N=C(Ph)-O-N(Me)-CH(Ph))]
      confirms the molecular structure and the trans configuration of the heterocycles
      relative to each other.

PMID- 18827938
TI  - New chemistry of olefin complexes of platinum(II) unravelled by basic conditions:
      synthesis and properties of elusive cationic species.
AB  - The evolution in basic medium ([RO-] = 1 M in methanol, R = H or Me) of five
      coordinate platinum(II) compounds, [PtCl2(eta2-C2H4)(N-N)], 2a-c, (N-N =
      N,N,N',N'-tetramethyl-1,2-ethanediamine, a; 2,2'-bipyridyl, b; 1,10
      phenanthroline, c) leads to the formation of [PtCl(eta1-CH2CH2-OCH3)(N-N)], 5a-c.
      The analogous compound 5d (N-N = 2,9-dimethyl-1,10-phenanthroline, d) can also be
      prepared, but not via transformation of the five-coordinate species 2d in basic
      medium where it is quite stable. 5d can instead be prepared by reaction of d with
      a strongly basic methanol solution of Zeise's anion [PtCl3(eta2-C2H4)](-), 1. In
      such a medium the di-anionic trans-[PtCl2(OR)(eta1-CH2CH2-OCH3)](2-) species (1")
      reacts with to form exclusively 5d. Hydrolysis of with acids bearing weakly
      coordinating anions leads to [PtCl(eta2-C2H4)(N-N)]+, 3a-c, as stable cations;
      upon the same treatment 5d does not generate 3d, but it reacts with HCl to give
      2d in almost quantitative yield. Cationic complexes 3b, 3c, here reported for the
      first time, were reacted with some nucleophiles and their behaviour compared with
      that of the already known 3a. In 3b, 3c the metal centre competes with the
      coordinated ethene for binding to nucleophiles; therefore the acetylacetonate
      anion can either add to the olefin (affording compounds 6b, 6c ) or to the metal
      ion replacing the ethene ligand (yielding compounds 7b, 7c). Under similar
      conditions, 3a gives exclusively 6a. Secondary amines readily add to ethene in
      3b, 3c, affording the addition products 8b, 8c, which undergo a ready cyclization
      to an azaplatinacyclobutane ring (9b, 9c). The remarkable ease of the four
      membered ring formation has been related to the high electrophilic character of
      the metal core in 3b, 3c.

PMID- 18827939
TI  - Binding of Ni2+ and Cu2+ ions to peptides with a Cys-His motif.
AB  - Waglerin I is a 22 amino acid snake venom toxin. Its three fragments (GGKPDLRPCHP
      NH2, PCHYIPRPKPR-NH2, PCHPPCHYIPR-NH2), due to the presence of two Cys and His
      residues, are potentially very attractive ligands for transition metal ions. The
      main aim of this work was to establish the impact of these two adjacent residues
      on Ni2+ ion binding, especially because this kind of motif is very common in
      nature, and the study of low molecular weight models could be helpful in
      understanding larger systems. In this work waglerin fragments and their N
      protected analogues were studied with Ni2+ (and Cu2+ for peptides with disulfide
      bridges) ions using combined potentiometric and spectroscopic measurements (UV
      Vis, CD, EPR and NMR). In all peptides, except PCHPPCHYIPR-NH2 with a disulfide
      bridge, the Cys-His motif was found to be crucial for the coordination of Ni2+
      ions. In the case of the N-unprotected analogues, the N-terminal amino group
      participates in the coordination as well.

PMID- 18827940
TI  - Influence of anionic sulfonate-containing co-ligands on the solid structures of
      silver complexes supported by 4,4'-bipyridine bridges.
AB  - In this paper, ten new silver compounds, namely [Ag(bipy)](L1).H2O (1),
      [Ag(bipy)](L2).2H2O (2), [Ag2(bipy)2(H2O)2](L3).H2O (3), [Ag(L4)(bipy)].H2O (4),
      [Ag(L5)(bipy)] (5), [Ag(L6)(bipy)].0.5CH3CN (6), [Ag3(L7)2(bipy)2].2(H2O) (7),
      [Ag2(L8)(bipy)1.5(H2O)].H2O (8), [Ag2(L9)(bipy)2(H2O)2] (9) and
      [Ag3(L10)(bipy)2][(bipy)(H2O)2].(H2O)3.5 (10) (where bipy = 4,4'-bipyridine, L1 =
      6-amino-1-naphthalenesulfonate anion, L2 = 2-naphthalenesulfonate anion, L3 =
      sulfosalicylate anion, L4 = p-aminobenzenesulfonate anion, L5 = 4
      dimethyaminoazobenzenen-4'-sulfonate anion, L6 = 2,5-dichloro-4-amino
      benzenesulfonate anion, L7 = 8-hydroxyquinoline-5-sulfonate anion, L8 = 2-nitroso
      1-naphthol-4-sulfonate anion, L9 = 2,6-naphthalenedisulfonate anion and L10 =
      1,3,5-naphthalenetrisulfonate anion), have been synthesized and characterized by
      elemental analyses, IR spectroscopy and X-ray crystallography. In compounds 1-6,
      Ag(I) centers are linked by bipy ligands to form 1D Ag-bipy chain structures, in
      which the sulfonate anions of compounds 1-3 act as counter ions. The sulfonate
      anions of compounds 4 and 5 connect Ag-bipy chains to form 1D double chain
      structures, respectively. The sulfonate anions of compound 6 connect Ag-bipy
      chains to form a 2D layer structure. Unexpectedly, compound 7 shows a hinged
      chain structure, and these chains interlace with each other through hydrogen
      bonds and pi-pi interactions to generate a 3D structure with channels along the c
      axis. Compounds 8 and 9 show 1D ladder-like structures. In compound 10, the Ag
      bipy chains are connected by sulfonate anions to generate a 3D poly-threaded
      network, in which an isolated Ag-bipy chain is inserted. The results indicate
      that the anionic sulfonate-containing co-ligands play an important role in the
      final structures of the Ag(I) complexes. Additionally, the luminescent properties
      of these compounds were also studied.

PMID- 18827941
TI  - Diversification of hydrothermal reaction products induced by temperature:
      syntheses, structures and properties of four La(III)-Cu(II) metal frameworks
      constructed from rod-shaped molecular building blocks.
AB  - The hydrothermal reaction of La(III), Cu(II) and 5-nitroisophthalic acid (H2NIPH)
      at different temperatures produced four novel coordination polymers,
      [LaCu(NIPH)(ONIPH)(H2O)4].H2O (1), [La2Cu(NIPH)4(H2O)6] (2), [La2Cu(NIPH)4(H2O)2]
      (3) and [LaCu(NIPH)2(HNIPH)(H2O)2].2H2O (4), (HONIPH = 2-hydroxy-5
      nitroisophthalate), these 2D and 3D frameworks are the first La(III)-Cu(II)
      heterometallic frameworks based on infinite rod-shaped molecular building blocks.
      In 1, a 2D layer is composed of infinite La-O-C-O-Cu rods consisting of
      alternating [La2O14(CO2)2] and [Cu2O8] units by corner sharing. The 3D frameworks
      of 2-4 are constructed from different rod-shaped molecular building blocks, which
      are linked by NIPH ligands to form a pcu-type rod packing arrangement.
      Interestingly, HONIPH came from the in situ hydroxylation of H2NIPH in the
      hydrothermal reaction.

PMID- 18827942
TI  - A series of manganese-carboxylate coordination polymers exhibiting diverse
      magnetic properties.
AB  - The hydrothermal reactions of an asymmetrical 4-(4-carboxyphenylamino)-3,5
      dinitrobenzoic acid (H2cpdba), MnCl2.4H2O, or together with 2,2'-bipyridine (2,2'
      bpy) or 4,4'-bipyridine (4,4'-bpy) afford three novel molecule-based magnetic
      coordination polymers [Mn(cpdba)]n (1), ([Mn2(cpdba)2(2,2'-bpy)2(H2O)2].H2O)n (2)
      and ([Mn2(cpdba)2(4,4'-bpy)].2H2O)n (3). Compound 1 has a 3D acentric
      coordination network containing carboxylate-bridged 1D ladder-like manganese
      chains with spin-canted antiferromagnetism (J = -3.51 cm(-1) for the coupling
      along the ladder legs, and zJ' = 0.22 cm(-1) for coupling along the ladder
      rungs), whereas compounds 2 and 3 crystallize in the centrosymmetric space groups
      P1 and C2/c, respectively. 2 exhibits a 1D chain structure, which is extended
      into a 3D supramolecular network by pi-pi stacking interactions, while 3 features
      a quite complex 3D network built up from the cpdba(2-) and 4,4'-bpy spacers as
      well as the carboxylate-bridged Mn(II) chains. Both 2 and 3 show weak
      antiferromagnetic coupling interactions (J = -0.55 cm(-1) for 2), and a field
      induced spin-flop magnetic transition can also be observed in 2 at ca. 3.2 T at 2
      K.

PMID- 18827943
TI  - Assembling metal phosphonates in the presence of monodentate-terminal and
      bidentate-bridging pyridine ligands. Use of non-covalent and covalent-coordinate
      interactions to build polymeric metal-phosphonate architectures.
AB  - The cubic transition metal phosphonates [(t)BuPO3M(2-apy)]4 (M= Zn (1), Co (2)),
      whose core resembles the D4R SBU of zeolites, have been synthesized from a
      reaction between the corresponding metal acetate, tert-butylphosphonic acid and 2
      aminopyridine (2-apy) at room temperature. X-Ray structure determination reveals
      that the molecules of 1 and 2, which crystallize in the tetragonal I4(1)/a space
      group with crystallographically imposed 4 symmetry, form a 3-D supramolecular
      assembly aided by N-H...O hydrogen bonding. When the same reaction was carried
      out by using a bridging bidentate Lewis base such as 4,4'-bipyridine, insoluble
      precipitate is obtained for both zinc and cobalt. In the case of other metal
      salts such as copper, manganese and nickel, however, one-dimensional polymeric
      compounds such as [M((t)BuPO3H)2(4,4'-bipy)(H2O)2]n (M= Cu (3), Mn (4)),
      [(Ni(4,4'-bipy)(H2O)4)((t)BuPO3H)2(H2O)]n (5) have been isolated. The solid-state
      structures of 3-5 have been determined by single crystal X-ray diffraction
      studies. Compounds 3 and 4 are isostructural and crystallize in the triclinic P1
      space group with two phosphonate ligands coordinated to the metal centers in a
      [1.100] fashion, whereas in the case of compound 5, the polymeric backbone is
      formed by Ni-4,4'-bipy units and the phosphonate anions show no bonding
      interaction to the metal. The 1-D polymeric chains of 3-5 organize in the solid
      state as 3-D supramolecular assemblies with the aid of extensive hydrogen bonding
      interaction between coordinated water molecules and P-OH or P=O groups of the
      phosphonate ligands.

PMID- 18827944
TI  - Effect of the ribose versus 2'-deoxyribose residue on the metal ion-binding
      properties of purine nucleotides.
AB  - The interaction between metal ions and nucleotides is well characterized, as is
      their importance for metabolic processes, e.g. in the synthesis of nucleic acids.
      Hence, it is surprising to find that no detailed comparison is available of the
      metal ion-binding properties between nucleoside 5'-phosphates and 2'
      deoxynucleoside 5'-phosphates. Therefore, we have measured here by potentiometric
      pH titrations the stabilities of several metal ion complexes formed with 2'
      deoxyadenosine 5'-monophosphate (dAMP2-), 2'-deoxyadenosine 5'-diphosphate (dADP3
      ) and 2'-deoxyadenosine 5'-triphosphate (dATP4-). These results are compared with
      previous data measured under the same conditions and available in the literature
      for the adenosine 5'-phosphates, AMP(2-), ADP(3-) and ATP(4-), as well as
      guanosine 5'-monophosphate (GMP(2-)) and 2'-deoxyguanosine 5'-monophosphate
      (dGMP(2-)). Hence, in total four nucleotide pairs, GMP(2-)/dGMP(2-), AMP(2
      )/dAMP(2-), ADP(3-)/dADP(3-) and ATP(4-)/dATP(4-) (= NP/dNP), could be compared
      for the four metal ions Mg2+, Ni2+, Cu2+ and Zn2+ (= M2+). The comparisons show
      that complex stability and extent of macrochelate formation between the phosphate
      coordinated metal ion and N7 of the purine residue is very similar (or even
      identical) for the AMP(2-)/dAMP(2-) and ADP(3-)/dADP(3-) pairs. In the case of
      the complexes formed with ATP(4-)/dATP(4-) the 2'-deoxy complexes are somewhat
      more stable and show also a slightly enhanced tendency for macrochelate
      formation. This is different for guanine nucleotides: the stabilities of the
      M(dGMP) complexes are clearly higher, as are the formation degrees of their
      macrochelates, than is the case with the M(GMP) complexes. This enhanced complex
      stability and greater tendency to form macrochelates can be attributed to the
      enhanced basicity (DeltapKaca. 0.2) of N7 in the 2'-deoxy compound. These results
      allow general conclusions regarding nucleic acids to be made.

PMID- 18827945
TI  - Coordination properties of cyclam (1,4,8,11-tetraazacyclotetradecane) endowed
      with two methylphosphonic acid pendant arms in the 1,4-positions.
AB  - The title ligand, 1,4,8,11-tetraazacyclotetradecane-1,4-diyl-bis(methylphosphonic
      acid) (H4te2p1,4, H4L), was prepared by an optimized synthetic approach and its
      complexing properties towards selected metal ions were studied by means of
      potentiometry. The ligand forms a very stable complex with copper(II) (log
      beta(CuL) = 27.21), with a high selectivity over binding of other metal ions
      (e.g. log beta(ZnL) = 20.16, log beta(NiL) = 21.92). The crystal structures of
      two intermediates in the ligand synthesis and two forms of the nickel(II) complex
      (obtained by crystallization at different pH) were determined. From acid
      solution, the crystals of trans-O,O-[Ni(H3L)]Cl.H2O were isolated. In such
      complex species, one phosphonate pendant arm is double- and the second arm is
      monoprotonated. The isolation of such species demonstrates a high kinetic
      inertness of the complex. The central metal ion is surrounded by four in-plane
      nitrogen atoms (in the ring configuration III) and two oxygen atoms of pendant
      moieties in the apical positions of octahedral coordination sphere. From neutral
      solution, the crystals of (trans-O,O-[Ni(H2L)])3.5H2O were isolated. The
      molecular structures of the complex units found in this structure are analogous
      to that found in trans-O,O-[Ni(H3L)]Cl.H2O.

PMID- 18827946
TI  - Reflection on tears and treatments.

PMID- 18827947
TI  - Comment on: A new look at lubrication of the ocular surface--fluid mechanics
      behind the blinking eyelids.

PMID- 18827948
TI  - Pterygium: evolution of medical and surgical treatments.

PMID- 18827949
TI  - The aging lacrimal gland: changes in structure and function.
AB  - The afferent nerves of the cornea and conjunctiva, efferent nerves of the
      lacrimal gland, and the lacrimal gland are a functional unit that works
      cooperatively to produce the aqueous component of tears. A decrease in the
      lacrimal gland secretory function can lead to dry eye disease. Because aging is a
      risk factor for dry eye disease, study of the changes in the function of the
      lacrimal gland functional unit with age is important for developing treatments to
      prevent dry eye disease. No one mechanism is known to induce the changes that
      occur with aging, although multiple different mechanisms have been associated
      with aging. These fall into two theoretical categories: programmed theories of
      aging (immunological, genetic, apoptotic, and neuroendocrine) and error theories
      of aging (protein alteration, somatic mutation, etc). Lacrimal glands undergo
      structural and functional alteration with increasing age. In mouse models of
      aging, it has been shown that neural stimulation of protein secretion is an early
      target of aging, accompanied by an increase in mast cells and lipofuscin
      accumulation. Hyperglycemia and increased lymphocytic infiltration can contribute
      to this loss of function at older ages. These findings suggest that an increase
      in oxidative stress may play a role in the loss of lacrimal gland function with
      age. For the afferent and efferent neural components of the lacrimal gland
      functional unit, immune or inflammatory mediated decrease in nerve function could
      contribute to loss of lacrimal gland secretion with age. More research in this
      area is critically needed.

PMID- 18827950
TI  - Compositional profiling and biomarker identification of the tear film.
AB  - Identification of tear film proteins and lipids is important for the elucidation
      of contact lens incompatibilities, tear film instabilities, dry eye syndromes,
      and other eye diseases. Compositional analysis of the tear film has been hampered
      in the past by the complex nature of the fluid and small sample size. Previously,
      all analytical methods required pooling of tear samples and molecular
      manipulation for detection of proteins and lipids, all of which skewed the
      resultant data. With the advent of nanoscale detection and analysis methods, it
      has become possible to identify specific tear components. This paper reviews the
      recent advances in tear sampling, proteomics, and lipidomics. Compositional
      profiling techniques, such as multi-dimensional electrophoresis, high performance
      liquid chromatography, and mass spectrometry, are assessed. Application of these
      techniques to identify potential biomarkers for specific tear disease conditions,
      such as blepharitis and dry eye, are evaluated.

PMID- 18827951
TI  - Corneal keloid.
AB  - Reports of corneal keloids are rare, with fewer than 80 cases published since the
      first case was documented in 1865. Keloids can be congenital or primary, but most
      often are associated with ocular surface injury or pathology. They have been
      reported in association with a number of congenital conditions, notably lowe's
      syndrome. Keloids are characterized histopathologically by a haphazard
      arrangement of fibroblasts, collagen bundles, and blood vessels. They have
      sometimes been confused with hypertrophic scars, but differ from such scars in
      that they may appear months or years after initial trauma and enlarge over time.
      The underlying cornea may be clear and uninvolved, or it may be opaque, depending
      on the primary pathology of the keloid. Treatment options include superficial
      keratectomy, lamellar or penetrating keratoplasty, and sclerokeratoplasty. The
      purpose of this review is to tabulate features of the reported corneal keloids,
      describing their etiologic, clinical, and histopathologic characteristics and
      discussing possible mechanisms of keloid formation.

PMID- 18827952
TI  - Clinical indications for ophthalmic corticosteroids.

PMID- 18827953
TI  - Butyltin contamination in industrialized bays associated with intensive marine
      activities in Korea.
AB  - Marine sediments and gastropod, Thais clavigera, were collected from
      industrialized areas and major harbors in Korea, to assess contamination sources
      and ecological risk to marine organisms by butyltin compounds such as tributyltin
      (TBT). TBT concentrations in sediments ranged from <LOD to 5372 ng Sn/g dry
      weight, and were comparable to or higher than concentrations in big harbors of
      other countries. The highest TBT concentrations were found in sediments close to
      shipyards in surveyed bays, suggesting that shipyard activities are a major
      contamination source of butyltins in Korean coastal waters. About half of the
      sediments showed potential risk of exceeding the guidelines and values proposed
      in in vivo studies. The occurrence of imposex in T. clavigera was 100% at all
      locations, indicating that the present levels of TBT contamination in
      industrialized bays in Korea are at concentrations reported to induce toxic
      effects on marine organisms, despite TBT's having been legally banned in Korea.

PMID- 18827954
TI  - A new anatomical technique to investigate nerves by imagery.
AB  - INTRODUCTION: We describe a novel post mortem technique that makes it possible to
      visualise the nerve structure of the brachial plexus using imaging. MATERIALS AND
      METHODS: We dissected in situ the brachial plexus of a cadaver preserved by
      formaldehyde. A preparation composed of a mixture of baryte powder, water and
      colorant, was applied to all sides of the brachial plexus and blood vessels of
      the region under study. A high resolution CT scan was performed. With the aid of
      Mimics (Materialise) software, segmentation of all the nerve and vascular
      structures on each of the 650 slices obtained was performed. The Mimics software
      then compiled all the slices to generate a 3-dimensional STL image. RESULTS: The
      image obtained was printed with a stereolythography printer, to produce a plastic
      model representing part of the cervico-thoracic spinal cord, the ribs, sternum,
      scapula, humerus, and clavicle, with the left brachial plexus and the subclavian,
      axillary and brachial veins and arteries. CONCLUSIONS: This technique has the
      potential for a wide range of uses: for teaching anatomy, to improve teaching of
      medical techniques, 3-dimensional modelisation of other nerve structures. The
      advantage is that the model obtained is a faithful and realistic reproduction.

PMID- 18827955
TI  - Signification of the unusual delineation of the anterior meniscofemoral ligament
      of Humphrey during knee arthro-CT.
AB  - BACKGROUND: Meniscofemoral ligaments (MFLs) are recognized as stabilizing and
      protective structures for the posterolateral meniscocondylar compartment of the
      knee, and as secondary restraints to tibial posterior translation. PURPOSE AND
      PATIENTS: We report the 64-row arthro-MDCT findings of 10 patients (8 males, 2
      females; mean age 43.8 years) in which the anterior MFL of Humphrey (aMLF) was
      atypically well delineated by an unusual circumferential effusion of iodine
      contrast. We discuss a possible physiopathologic mechanism for this effusion,
      describe the MDCT anatomy of the aMLF and review the literature about the anatomy
      and physiology of the MFLs. RESULTS: In each of our ten patients an unusual
      effusion of articular contrast was found delineating a posterior oblique
      ligamentar bundle, which was running in front of the posterior cruciate ligament
      (PCL). This bundle was best appreciated on posterior coronal oblique and sagital
      MPR views, and was recognized as the aMFL. The finding was associated with a
      partial tear of the tibial insertion of the posterior horn (PH) of the lateral
      meniscus (LM) in three patients, and with a partial (two cases) or subtotal
      (three cases) tear of the PCL in five patients. A swollen-probably oedematous-PCL
      was found in another patient and in the last case the anomaly was minimal and
      remained isolated. All patients were treated conservatively. CONCLUSION: Since
      the aMFL inserts inferiorly into the posterior horn of the LM and runs in very
      close anatomic and functional relation with the PCL, we hypothesize that a trauma
      producing a tear in these structures may also occasionally sufficiently stretch
      the aMFL to produce a peripheral loosening allowing a circumferential effusion of
      opacified synovial fluid around the ligament. Our report offers the opportunity
      to illustrate the "in vivo" anatomy of the aMFL through original unpublished
      figures. It also contributes to reinforce the literature data concerning the
      potential fine mechanical role played by the LM-MFLs-PCL complex, in which the
      centrally located MFLs act laterally as stabilizing and protective structures for
      the posterolateral meniscocondylar compartment and medially as secondary
      restraints to tibial posterior translation.

PMID- 18827956
TI  - Serotonin transporter (5-HTTLPR) and monoamine oxidase (MAOA) promoter
      polymorphisms in women with severe alcoholism.
AB  - The serotonin system is known to play a pivotal role for mood, behaviour and
      psychic illness as e.g. alcoholism. Alcoholism in both males and females has been
      associated with polymorphisms in genes encoding for proteins of importance for
      central serotonergic function. Genotyping of two functional polymorphisms in the
      promoter region of the serotonin transporter and monoamine oxidase-A,
      respectively, (5-HTT-LPR and MAOA-VNTR), was performed in a group of women with
      severe alcohol addiction. A large sample of adolescent females from a normal
      population was used as controls. A significantly higher frequency of the LL 5-HTT
      genotype (high activity) was found in female addicts without a known co-morbid
      psychiatric disorder than in the controls. Genotype of the MAOA-VNTR polymorphism
      did not differ significantly between addicts and controls. However, within the
      group of alcoholics, when the patients with known co-morbid psychiatric disorders
      were excluded, aggressive anti-social behaviour was significantly linked to the
      presence of the high activity MAOA allele. The pattern of associations between
      genotypes of 5-HTT-LPR and MAOA-VNTR in women with severe alcoholism differs from
      most corresponding studies on males.

PMID- 18827957
TI  - Metformine for psychosis associated with the menstrual cycle in a patient with
      polycystic ovary syndrome.
AB  - There are several reports of periodic psychotic disorders that appear in
      connection with the various phases of the menstrual cycle. Although the
      pathogenesis of menstrual psychosis has not been systematically investigated, it
      appears that it might be linked to an estrogen cascade that follows a period of
      sustained high estrogen levels, as in the case in anovulatory cycles. We present
      a case of psychosis associated with the menstrual cycle in a patient with
      polycystic ovary syndrome, a disorder typically characterized by anovulatory
      cycles, in whom the restoration of normal menstruation with use of metformine led
      to significant improvement of psychotic symptoms.

PMID- 18827958
TI  - Hemarthrosis as acute presentation of acquired hemophilia in a patient with
      systemic lupus erythematosus: successful treatment and long-lasting remission.
AB  - Hemorrhagic events due to production of antibodies directed against coagulation
      factors are rarely observed in systemic lupus erythematosus (SLE). We report the
      case of a patient with clinically quiescent SLE who developed factor VIII
      inhibitor in acquired hemophilia presenting as hemarthrosis. Initial treatment
      with FVII, FVIII and FIX plasma concentrate, metilprednisolone and
      immunoglobulins i.v. were started but new hemorrhagic manifestation occurred.
      Plasma exchange was also administered, but it was discontinued early due to
      partial efficacy. In addition, pulse cyclophosphamide 0.5 g/m(2) was started.
      Eight weeks later, FVIII and FIX activity returned within normal ranges, FVIII
      and FIX inhibitors decreased significantly and hemorrhagic manifestations
      disappeared. The rare occurrence of acquired hemophilia due to the presence of
      anti-factor VIII antibodies associated to SLE, which was reviewed, might explain
      the lack of therapeutic guide-lines; indeed therapeutic options are available but
      the outcome in each single patient is not predictable.

PMID- 18827959
TI  - Iatrogenic Cushing's syndrome and secondary adrenal insufficiency after a single
      intra-articular administration of triamcinolone acetonide in HIV-infected
      patients treated with ritonavir.
AB  - The development of an iatrogenic Cushing's syndrome (ICS) followed by secondary
      adrenal failure remains an exceptional event after a single dose administration
      of a synthetic glucocorticoid. Medical attention has been drawn recently on the
      possible impact of ritonavir-based antiretroviral regimens on the systemic
      deleterious effects of a chronic administration of corticosteroids in HIV
      infected patients. Three HIV-infected patients treated by a ritonavir-boosted
      protease inhibitor (PI) regimen received a single intra-articular injection of 40
      mg triamcinolone acetonide in our university hospital. The three patients rapidly
      developed signs and symptoms of ICS followed by secondary adrenal insufficiency.
      Special attention must be paid when a single administration of corticosteroids
      has to be given in HIV-positive patients under ritonavir-boosted antiretroviral
      treatment, as these patients are at risk of developing early cushingoid features
      and a prolonged suppression of their hypothalamic-pituitary-adrenal axis.

PMID- 18827960
TI  - Digital vasculitis: a late complication of anti-tumour necrosis factor alpha
      therapy.
AB  - Anti-tumour necrosis factor alpha therapy has led to significant advancement in
      the treatment of rheumatological disease. Rarely, anti-TNFalpha antagonists have
      been associated with vasculitis, predominantly cutaneous leukocytoclastic
      vasculitis. We present the first case of angiographically-confirmed digital
      vasculitis occurring as a late complication of etanercept therapy. Our case adds
      to the limited repertoire of case reports of anti-TNFalpha induced vasculitis and
      highlights the potential risk of this serious complication occurring up to
      several years after initiation of these agents.

PMID- 18827961
TI  - Serum and synovial fluid levels of p40 IL12/23 in spondyloarthropathy patients.
AB  - IL-23 is the main inductor in Th17 polarization of naive T cells, inducing IL-17
      production. IL-17 has been demonstrated to be elevated in ankylosing spondylitis
      (AS). The p40 subunit is common to IL-12 and IL-23. We assessed serum and
      synovial levels of p40 IL12/23 in spondyloarthropathy (SpA) patients and the
      evolution under anti-TNF. SpA patients fulfilling ESSG criteria were included.
      Healthy volunteers served as controls. P40 IL12/23 was assessed using Human
      Quantikine ELISA (R&D Systems), and at the same time, BASDAI, ESR, CRP, IL-17,
      MMP-3. Patients treated with anti-TNF were evaluated again after 10 weeks of
      treatment. Statistical analysis used Mann Whitney and correlation tests. Twenty
      seven SpA outpatients (20 men), mean age 40.3 years, mean disease duration 10.5
      years, HLA B27 positive n = 21, peripheral arthritis n = 8, mean BASDAI 45.7,
      mean CRP 30.7 mg/l, and 24 controls (12 men), mean age 50.4 years, were included.
      There is no statistical difference in serum levels of p40IL12/23 between patients
      (mean 77.8 pg/ml) and controls (103 pg/ml) and between patients with axial and
      peripheral involvement. Levels were higher in HLA B-27 negative patients (p =
      0.02). No statistical correlation was found between p40 IL12/40 serum levels and
      each of BASDAI, ESR, CRP, serum levels of IL 17, MMP 3. Fourteen AS patients were
      treated with TNF blockers. Whereas significant reduction in BASDAI, ESR, and CRP
      were obvious after treatment, there was no significant change in serum level of
      p40 IL12/23. Mean levels of synovial p40 IL12/23 were higher in SpA patients (n =
      6; mean 536 pg/ml) compared to osteoarthritis patients (n = 3; 133 pg/ml) and
      compared with paired serum SpA levels. These results suggest that serum levels of
      p40 IL-12/23 may not be considered as a biologic tool of disease activity
      assessment in SpA patients.

PMID- 18827962
TI  - Laser Florence 2008. Abstracts of the International Congress of Laser Medicine.

PMID- 18827963
TI  - Simple sampling strategy for measuring inulin renal clearance.
AB  - BACKGROUND: In the standard method of inulin clearance (Cin), three sets of serum
      and urine samples are collected during a 2-hour clearance period. For a practical
      use of this method, sampling should be the minimal number allowable while still
      providing enough accuracy. The aim of this study was to evaluate the validity of
      inulin renal clearance with assumed single urine collection with a period such as
      30, 60 or 90 minutes. METHODS: Inulin clearance data collected by the standard
      method from 737 individuals were used. Changes of serum inulin concentrations
      between 45 and 105 minutes after the start of the infusion were analyzed. We used
      first urine collection to calculate the inulin clearance with single urine
      collection (Cin-30 min). We assumed single urine collection for 60 or 90 minutes
      by combining the urine data of the consecutive 30-minute periods. Inulin
      clearances (Cin-60 min, Cin-90 min) were calculated from the assumed single urine
      collections, respectively. RESULTS: Serum inulin concentration did not reach
      equilibrium during the clearance period. It increased in subjects with low
      glomerular filtration rate (GFR) and decreased in subjects with normal GFR. The
      amount of the change was small and -0.5 +/- 12.6% in subjects with GFR over 30
      ml/min per 1.73 m(2). Cin-30 min, Cin-60 min and Cin-90 min showed high
      correlation coefficients against Cin-ST (0.962, 0.988 and 0.998, respectively).
      Systemic biases in these clearances were negligible (under 1 ml/min per 1.73
      m(2)). Root mean square error (RMSE) were 10.4, 5.3 and 2.3 ml/min per 1.73 m(2)
      for Cin-30 min, Cin-60 min and Cin-90 min, respectively. These data indicated
      that accuracy of inulin clearance depends on the duration of the urine collection
      period. CONCLUSION: Inulin clearance with a single urine collection is a
      convenient method. We showed that single urine collection for 30 minutes or a
      longer period has reasonable accuracy in calculation of inulin clearance. We
      propose a method of inulin clearance with single urine collection for 60 minutes.

PMID- 18827964
TI  - Contribution of T lymphocytes to rat renal ischemia/reperfusion injury.
AB  - BACKGROUND: This study aimed to elucidate the early involvement of T lymphocytes
      in renal ischemia/reperfusion injury. METHODS: Athymic nude rats (F344/N_Jcl-nu)
      and control F344/Jcl were subjected to 45 min unilateral renal ischemia. To
      determine whether the observed differences might be derived from the T lymphocyte
      presence, T lymphocytes from the spleens of F344/Jcl were injected into
      F344/N_Jcl-nu via tail vein at the initiation of reperfusion. Immunohistochemical
      analysis was performed for CD3, the proliferative cell nuclear antigen (PCNA),
      vimentin, and E-cadherin. T lymphocytes were obtained from the green fluorescent
      protein transgenic (GFP) rats, and transplanted to F344/N_Jcl-nu 10 min before
      reperfusion. The animals were euthanized 15 min after reperfusion. RESULTS:
      F344/N_Jcl-nu showed less retention of both Cr and BUN at 24 and 48 h after
      reperfusion, compared with F344/Jcl. F344/N_Jcl-nu received T lymphocyte
      transplantation showed significantly higher retention of both Cr and BUN 24, 48,
      and 72 h after reperfusion than those without T lymphocyte. A rapid infiltration
      of T lymphocytes into proximal tubular epithelial cells and tubular lumen was
      observed using T lymphocytes with green fluorescent protein. In contrast, T
      lymphocytes were observed with much less frequency 24 h after ischemia. The
      number of PCNA-positive proximal tubular cells 24 h after the initiation of
      reperfusion was significantly smaller in the T lymphocyte transplantation group
      compared with the non-transplantation group. The vimentin positivity and
      cytoplasmic staining of E-cadherin were also more prominent in the
      transplantation group. CONCLUSION: These findings demonstrate a rapid renal T
      lymphocyte infiltration, which propagate renal functional deterioration.

PMID- 18827966
TI  - Acute oxygen-ozone administration to rats protects the heart from ischemia
      reperfusion infarct.
AB  - OBJECTIVE AND DESIGN: We tested here the effects of acute administration of an
      oxygen/ozone (O3) mixture on the myocardial tissue damage following an ischemic
      event. MATERIAL OR SUBJECTS: The study was done in Sprague-Dawley rats subjected
      to acute myocardial ischemia/reperfusion (I/R). TREATMENT: 100; 150; and 300
      microg/kg oxygen/O3 mixture were insufflated intraperitoneally 1 h prior to I/R.
      METHODS: Myocardial infarct size measurement and immunhistochemistry or ELISA for
      nitrotyrosine, CD68, CD8,CD4 and caspase-3 were done. RESULTS: I/R produced a
      marked damage in the rat left ventricle with an infarct size as percentage of the
      area at risk (IS/ AR) of approximately 45 +/- 4% . Rats insufflated with a
      oxygen/O3 mixture showed a significant 2-h cardio-protection (e. g. infarct size
      over area at risk for the dose of 300 microg/kg was approximately 30 +/- 3%,) as
      compared with control rats (P <0.01). This effect was paralleled by a decrease in
      tissue levels of immunostaining for biomarkers of nitrosative stress
      (nitrotyrosine), inflammation (CD68) and immunity response (CD8 and CD4) between
      heart tissues from infarcted rats and infarcted O3 treated rats. CONCLUSIONS:
      These data indicate that the tissue and biochemical damages associated with
      myocardial ischemia/reperfusion can be counteracted by an acute O3 pretreatment.

PMID- 18827965
TI  - Serofendic acid protects from iodinated contrast medium and high glucose probably
      against superoxide production in LLC-PK1 cells.
AB  - BACKGROUND: It is well known that patients with chronic kidney disease, including
      diabetic nephropathy, often develop cardiovascular diseases. In case of
      radiographic procedures, reduced renal function may be deteriorated by the use of
      iodinated contrast medium (CM). This is known as CM-induced nephropathy. In this
      study, we have focused on the mechanisms of this type of injury in diabetic
      nephropathy and the preventive effects of serofendic acid. METHODS: We evaluated
      the cytotoxicity of CM and high glucose on tubular epithelial cells using an LLC
      PK1 cell line, and measured cell viability with an alamarBlue assay. We further
      evaluated superoxide production levels measured by dihydroethidium. We also
      examined the protective effects of serofendic acid on cytotoxicity with
      superoxide production of CM and high glucose. RESULTS: CM reduced cell numbers in
      a dose-dependent and time-dependent manner in LLC-PK1 cells. Furthermore,
      cytotoxicity of CM in diluted concentration was additively influenced by high
      glucose. CM and high glucose increased superoxide production, which was evaluated
      by the response to dihydroethidium, and was suppressed by serofendic acid.
      Cytotoxicity of CM, high glucose, and H(2)O(2) was suppressed by serofendic acid,
      as well as the suppression by N-acetylcysteine on CM toxicity. Interestingly, the
      recovery by serofendic acid in H(2)O(2)- and high glucose-induced cellular injury
      was to the basal level, in contrast with the partial recovery from CM-induced
      injury. Finally, serofendic acid suppressed CM-induced injury and high glucose
      induced apoptosis. CONCLUSIONS: These results suggest that CM and high glucose
      induce cytotoxicity and oxidative stress in LLC-PK1 cells and that serofendic
      acid protects the injury probably from superoxide generation.

PMID- 18827967
TI  - Fluctuation of annexin-A1 positive mast cells in chronic granulomatous
      inflammation.
AB  - OBJECTIVE: We have applied here a model of chronic granulomatous inflammation to
      study the profile of mast cell activation and their expression of annexin-A1 in
      the nodular lesion. MATERIALS: Granulomatous inflammation was induced by
      injection of croton oil and Freund's complete adjuvant (CO/FCA) into the dorsal
      air-pouches of mice. Skin tissue samples were collected from control group (24 h
      time-point; i. e. before disease development) and 7, 14, 21, 28 and 42 days post
      CO/FCA treatment. RESULTS: Histopathological analyses revealed an on-going
      inflammation characterized by an increased number of activated mast cells at
      sites of the chronic inflammatory reaction in all experimental groups.
      Immunohistochemical analysis showed skin mast cells highly immunoreactive for
      annexin-A1, both at an initial (day 7) and a delayed (day 28) phase of the
      inflammatory reaction. CONCLUSIONS: The observed time-dependent modulation of
      mast cell activation, during the granulomatous injury, indicates that multiple
      pathways centred on annexin-A1 might become activated at different stages of this
      chronic inflammatory response, including the delayed and pro-resolving phase.

PMID- 18827968
TI  - Treatment with bindarit, an inhibitor of MCP-1 synthesis, protects mice against
      trinitrobenzene sulfonic acid-induced colitis.
AB  - OBJECTIVE: Chemokines play a fundamental role in trafficking and activation of
      leukocytes in colonic inflammation. We investigated the ability of bindarit, an
      inhibitor of monocyte chemoattractant protein-1 (MCP-1/CCL2) synthesis, to
      inhibit chemokine production by human intestinal epithelial cells (HT-29) and its
      effect in trinitro-benzene sulfonic acid (TNBS)-induced colitis in mice.
      MATERIALS AND METHODS: HT-29 cells were incubated with bindarit in the presence
      of TNF-alpha/IFN-gamma and 24 h later supernatants were collected for MCP-1, IL-8
      and RANTES measurement. A 1 mg enema of TNBS was given to BALB/c mice, and
      bindarit (100 mg/kg) was orally administered twice daily starting from two days
      before colitis induction. Weight loss, histology, and MCP-1 level and
      myeloperoxidase (MPO) activity in colon extracts were assessed. RESULTS: In HT-29
      cells, bindarit concentration-dependently and selectively inhibited MCP-1
      secretion (as well as mRNA expression) primed by TNF-alpha/IFN-gamma. Moreover
      treatment with bindarit reduced clinical and histopathological severity of TNBS
      induced colitis. These effects were associated with significant inhibition of MCP
      1 and MPO in colon extracts. CONCLUSIONS: Bindarit exhibits a potent bioactivity
      in reducing leukocyte infiltration, down-regulating MCP-1 synthesis, and
      preventing the development of severe colitis in a mice model of TNBS-induced
      colitis. These observations suggest a potential use of MCP-1 synthesis blockers
      in intestinal inflammation in humans.

PMID- 18827969
TI  - Interleukin-12p40 contributes to protection against lung injury after oral
      Yersinia enterocolitica infection.
AB  - OBJECTIVE: The impact of Yersinia enterocolitica on lung is incompletely
      understood, so we studied the inflammatory effects of Yersinia oral infection and
      the influence of IL-12p40 deficiency. METHODS: Wild-type (WT) and IL-12p40-/-
      (KO) mice were orally infected with Y. enterocolitica 0:3. After 3 and 21 days,
      cell viability in bronchoalveolar lavage (BAL) fluid, inflammatory reactions,
      lipid hydroperoxides, antioxidant enzyme expression and histological changes were
      studied. RESULTS: An effect on the lung was demonstrated by changes in lactate
      dehydrogenase, total protein (p <0.001), nitrosative stress and increase numbers
      of lymphocyte in the BAL fluid. All of these appeared to be IL-12 - independent
      since statistically significant changes in response to infection (at 21 days) did
      not differ between WT and KO groups. However, a protective role of IL-12 after
      infection was suggested by a decrease in cell viability, histopathological
      changes, different cell populations, higher lipid peroxidation and a decrease in
      antioxidant enzymes - glutathione peroxidase, superoxide dismutase-2 (p <0.05).
      The main changes were detected at day 21 suggesting a chronic effect of Yersinia
      infection and that IL-12 could play a role in the protection against chronic
      sequelae in the lung. CONCLUSIONS: These results demonstrate that Y.
      enterocolitica infection may induce inflammatory response in lung and that IL
      12p40 could contribute to protection against lung injury.

PMID- 18827970
TI  - Strain and model dependent differences in inflammatory cell recruitment in mice.
AB  - OBJECTIVE AND DESIGN: The objective of this study was to determine genetic
      differences in inflammation in these distinct inbred mouse strains. METHODS:
      Peritoneal leukocyte recruitment, matrix metalloproteinases and cytokines were
      quantified in A/J, 129/svJ, C57BL/6J, using thioglycollate or biomaterial
      implants as inflammatory stimuli. RESULTS: In response to thioglycollate, A/J had
      significant decreases compared to C57BL/6J in both neutrophil (86 %) and
      macrophage (62 %) recruitment, and 129/svJ had a significant (43 %) decrease
      compared to C57BL/6J in macrophage recruitment. The reduced leukocyte recruitment
      corresponded to reduced matrix metalloproteinase-9. In the bioimplant model,
      129/svJ had a 2-fold increase in neutrophil and macrophage recruitment compared
      to C57BL/6J, and the increased leukocyte recruitment corresponded to elevated
      cytokines, monocyte inhibitory protein-2 and monocyte chemoattractant protein-1,
      in the lavage compared to the values for C57BL/6J. CONCLUSION: Not only was
      leukocyte recruitment strain dependent, but the three strains had marked
      differences in metalloproteinases and cytokine response. In addition, there were
      model specific differences in the metalloproteinase and cytokine response to the
      two inflammatory stimuli. Thus, inflammatory cell recruitment is genetically
      determined and stimulus specific and may determine the susceptibility to complex
      diseases.

PMID- 18827971
TI  - Inhibition of Ca2+ influx by surfactant in NR8383 alveolar macrophages.
AB  - OBJECTIVE: Pulmonary surfactants reduce alveolar surface tension and alter
      inflammatory cell function. We studied the effects of surfactant preparations on
      Ca2+ influx regulated by protein kinase C (PKC) and mitogen-activated protein
      kinases (MAPK) and cytokine secretion in the alveolar macrophage (AM) cell line
      NR8383. METHODS: Fura-2-loaded AMs were stimulated with zymosan (200 microg/ml),
      1,2-dioctanoyl-sn-glycerol (DOG, 20 microM) or C6-ceramide (C6C, 10 microM) in
      the presence of exogenous surfactants (beractant, calfactant or colfosceril) or
      surfactant phospholipid (dipalmitoyl phosphatidylcholine, DPPC), at 250 microg/ml
      phospholipid and changes in cytosolic free Ca2+ (Delta[Ca2+]i) and cytokines were
      measured. RESULTS: Zymosan-induced Delta[Ca2+]i (117 +/- 5 nM) at 3 min was
      reduced (p <0.001) by beractant (50 +/- 6 nM), colfosceril (61 +/- 2 nM),
      calfactant (46 +/- 5 nM), and DPPC (52 +/- 5 nM). Beractant inhibited the
      Delta[Ca2+]i by PKC stimulation with DOG and all preparations reduced the MAPK
      induced Ca2+ influx by C6C. Beractant and Ca2+ channel blocker SKF 96365 (10
      microM) together abolished the zymosan-stimulated Delta[Ca2+]i. Zymosan
      stimulated TNF-alpha and IL-1beta secretion was also inhibited by surfactant
      pretreatment. CONCLUSIONS: These results indicate that exogenous surfactant
      inhibits Ca2+ influx and cytokine secretion in zymosan-stimulated AMs. This anti
      inflammatory activity may be through an interaction with downstream signaling
      elements or Ca2+ channels.

PMID- 18827972
TI  - Solution NMR structure determination of proteins revisited.
AB  - This 'Perspective' bears on the present state of protein structure determination
      by NMR in solution. The focus is on a comparison of the infrastructure available
      for NMR structure determination when compared to protein crystal structure
      determination by X-ray diffraction. The main conclusion emerges that the unique
      potential of NMR to generate high resolution data also on dynamics, interactions
      and conformational equilibria has contributed to a lack of standard procedures
      for structure determination which would be readily amenable to improved
      efficiency by automation. To spark renewed discussion on the topic of NMR
      structure determination of proteins, procedural steps with high potential for
      improvement are identified.

PMID- 18827973
TI  - Stable isotope labeling of protein by Kluyveromyces lactis for NMR study.
AB  - Stable isotope labeling for proteins of interest is an important technique in
      structural analyses of proteins by NMR spectroscopy. Escherichia coli is one of
      the most useful protein expression systems for stable isotope labeling because of
      its high-level protein expression and low costs for isotope-labeling. However,
      for the expression of proteins with numerous disulfide-bonds and/or post
      translational modifications, E. coli systems are not necessarily appropriate.
      Instead, eukaryotic cells, such as yeast Pichia pastoris, have great potential
      for successful production of these proteins. The hemiascomycete yeast
      Kluyveromyces lactis is superior to the methylotrophic yeast P. pastoris in some
      respects: simple and rapid transformation, good reproducibility of protein
      expression induction and easy scale-up of culture. In the present study, we
      established a protein expression system using K. lactis, which enabled the
      preparation of labeled proteins using glucose and ammonium chloride as a stable
      isotope source.

PMID- 18827974
TI  - Typology reconfigured: from the metaphysics of essentialism to the epistemology
      of representation.
AB  - The goal of this paper is to encourage a reconfiguration of the discussion about
      typology in biology away from the metaphysics of essentialism and toward the
      epistemology of classifying natural phenomena for the purposes of empirical
      inquiry. First, I briefly review arguments concerning 'typological thinking',
      essentialism, species, and natural kinds, highlighting their predominantly
      metaphysical nature. Second, I use a distinction between the aims, strategies,
      and tactics of science to suggest how a shift from metaphysics to epistemology
      might be accomplished. Typological thinking can be understood as a scientific
      tactic that involves representing natural phenomena using idealizations and
      approximations, which facilitates explanation, investigation, and theorizing via
      abstraction and generalization. Third, a variety of typologies from different
      areas of biology are introduced to emphasize the diversity of this
      representational reasoning. One particular example is used to examine how there
      can be epistemological conflict between typology and evolutionary analysis. This
      demonstrates that alternative strategies of typological thinking arise due to the
      divergent explanatory goals of researchers working in different disciplines with
      disparate methodologies. I conclude with several research questions that emerge
      from an epistemological reconfiguration of typology.

PMID- 18827975
TI  - A comparison of direct thrombin inhibitors in the treatment of Heparin-Induced
      Thrombocytopenia: a single institution experience.
AB  - BACKGROUND AND OBJECTIVE: Heparin-Induced Thrombocytopenia (HIT), if left
      untreated, can lead to thrombocytopenia, thromboembolic complications and even
      death. Two thrombin inhibitors, lepirudin and argatroban, have been shown to
      improve clinical outcomes compared to historical controls in the management of
      HIT. The purpose of this retrospective study was to compare the effects of
      lepirudin and argatroban in the management of HIT. METHODS: Adult subjects with a
      positive anti-heparin platelet factor 4 (PF4) antibody test and >50% decrease in
      platelet count during the first 30 days of admission over a period of 2 years
      were included in the study. Patient demographics, platelet counts, choice of
      antithrombin therapy, occurrence of thrombosis, length of hospital stay, and date
      and cause of death, if applicable, were collected for each patient. RESULTS:
      Eighty-two patients met inclusion criteria: 41 patients did not receive any
      thrombin inhibitors after the diagnosis of HIT, 24 patients received lepirudin
      and 17 patients received argatroban. Subjects treated with a thrombin inhibitor
      were more likely to experience platelet count recovery (87.5% for the lepirudin
      group and 82.4% for the argatroban group) compared to those who did not receive
      antithrombin therapy (51.2%) after the diagnosis of HIT was made (P < 0.001). The
      thrombosis rate for subjects who did not receive antithrombin therapy after the
      diagnosis of HIT was 26.8%, compared to 8.3% for the lepirudin group and 5.9% for
      the argatroban group (P < 0.01). The incidence of death was also higher in the
      group of subjects that did not receive antithrombin therapy (48.8%) compared with
      the lepirudin group (16.7%) or the argatroban group (23.5%), P < 0.01.
      CONCLUSION: Our findings suggest that thrombin inhibitors can improve the
      outcomes of patients with HIT by decreasing the incidence of morbidity and
      mortality relating to HIT. No significant difference could be determined in
      outcomes between argatroban and lepirudin therapy.

PMID- 18827976
TI  - Quality of oral anticoagulant therapy in patients who perform self management:
      warfarin versus phenprocoumon.
AB  - BACKGROUND: The quality of oral anticoagulant therapy may be related to which
      type of coumarin is used. The aim was to investigate whether phenprocoumon or
      warfarin provide the highest quality of oral anticoagulant therapy in patients
      who manage the therapy themselves. METHODS AND RESULTS: In a cohort study 519
      patients on self managed oral anticoagulant therapy were included. Quality
      control parameters, were, the percentage of time spent in the therapeutic range
      and the variability in the patients' INR values. Time within therapeutic INR
      target range in the patient group treated respectively with warfarin and
      phenprocoumon was 70.2% and 74.0% (P = 0.008).The median variance in the warfarin
      group was 0.35 (95% CI (0.32-0.38)) and 0.29 (95% CI (0.25-0.33)) in the
      phenprocoumon group (P = 0.0004). CONCLUSION: Phenprocoumon provides a higher
      percentage of time spent in therapeutic INR interval and a lower variation of INR
      values compared with warfarin.

PMID- 18827977
TI  - Dark chocolate: consumption for pleasure or therapy?
AB  - Traditional chocolate is derived from the cocoa bean, which is one of the most
      concentrated sources of flavanols, a subgroup of the natural antioxidant plant
      compounds called flavonoids. Accumulating evidence from the past 10 years
      demonstrates that moderate consumption of chocolate, especially dark chocolate,
      may exert protective effects against the development of cardiovascular disease.
      Several mechanisms have been proposed to explain this positive influence,
      including metabolic, antihypertensive, anti-inflammatory, and anti-thrombotic
      effects, as well as effects on insulin sensitivity and vascular endothelial
      function. Should these results be confirmed in randomised, controlled, cross
      over, multi-dose trials, then the pleasure associated with chocolate consumption
      might also be justified from health and psychological perspectives. However,
      since dark chocolate has substantially higher levels of flavonoids than milk
      chocolate, and milk proteins may inhibit absorption of flavonoids, it might be
      preferable to consume dark chocolate than the white (milk) variety.

PMID- 18827978
TI  - The synergistic induction of cyclooxygenase-2 in lung fibroblasts by angiotensin
      II and pro-inflammatory cytokines.
AB  - Although we have demonstrated that Angiotensin II (Ang II) signaling plays a role
      in colon and lung tumorigenesis, the precise mechanisms by which Ang II
      stimulates tumorigenesis remain unclear. The aim of this study was to investigate
      the synergistic induction of COX-2 by Ang II and pro-inflammatory cytokines in
      lung fibroblasts. We also compared the efficiencies of Ang II-dependent COX-2
      induction in lung epithelial cells and stromal cells. Ang II induced COX-2
      expression in lung fibroblasts in a dose-dependent manner (10(-9) to 10(-7) M)
      through the Ang II subtype 1 receptor (AT(1)). In addition, Ang II
      synergistically stimulated the induction of COX-2 by pro-inflammatory cytokines,
      IL-1beta, or TNF-alpha. Our results indicate that the pro-tumorigenic function of
      Ang II is attributable, in part, to its strong stimulatory effect of COX-2
      expression in lung fibroblasts in which synergistic stimulation with pro
      inflammatory cytokines was evident. It is also suggested that the AT(1) receptor
      in lung fibroblasts may be a rational target for chemoprevention of lung cancer.

PMID- 18827979
TI  - The effects on cell growth and chemosensitivity by livin RNAi in non-small cell
      lung cancer.
AB  - Livin is highly expressed in most tumor tissues and could inhibit the tumor cells
      apoptosis. Knockdown of endogenous livin expression in non-small cell lung cancer
      (NSCLC) cells could inhibit cell growth. But it is still unclear if knockdown of
      endogenous livin expression combined with conventional chemotherapy could play a
      positive role in NSCLC treatment. In this article, the efficient RNA
      interferences (RNAi) of livin were constructed, and then we transfected them into
      A549 cells and 103H cells to study their influence on cell cycle and apoptosis
      index. At last, we detected the cell's sensitivity to conventional
      chemotherapeutic drugs after knockdown endogenous livin expression in A549 cells
      and 103H cells. Our results showed that knockdown livin expression could inhibit
      cell growth and induce apoptosis in A549 cells and 103H cells. A549 cells and
      103H cells had an increased chemosensitivity to adriamycin and cisplatin after
      transfection of livin RNAi constructs. The results indicated that cell cycle
      redistribution and increased apoptosis index after knockdown livin expression
      might provide the main explanation for the enhanced chemosensitivity. Proper
      combination of livin RNAi and some conventional chemotherapeutic drugs may entail
      potential benefits in the treatment of NSCLC.

PMID- 18827980
TI  - How human leukocytes track down and destroy pathogens: lessons learned from the
      model organism Dictyostelium discoideum.
AB  - Human leukocytes, including macrophages and neutrophils, are phagocytic immune
      cells that capture and engulf pathogens and subsequently destroy them in
      intracellular vesicles. To accomplish this vital task, these leukocytes utilize
      two basic cell behaviors-chemotaxis for chasing down infectious pathogens and
      phagocytosis for destroying them. The molecular mechanisms controlling these
      behaviors are not well understood for immune cells. Interestingly, a soil amoeba,
      Dictyostelium discoideum, uses these same behaviors to pursue and injest its
      bacterial food source and to organize its multi-cellular development.
      Consequently, studies of this model system have provided and will continue to
      provide us with mechanistic insights into the chemotaxis and phagocytosis of
      immune cells. Here, we review recent research in these areas that have been
      conducted in the Chemotaxis Signal Section of NIAID's Laboratory of
      Immunogenetics.

PMID- 18827981
TI  - Amplification mechanisms for the enhancement of antigen-mediated mast cell
      activation.
AB  - Activation of mast cells in the allergic inflammatory response occurs via the
      high affinity receptor for IgE (FcepsilonRI) following receptor aggregation
      induced by antigen-mediated cross-linking of IgE-occupied FcepsilonRI. Recent
      observations suggest this response is profoundly influenced by other factors that
      reduce the threshold for, and increase the extent of, mast cell activation. For
      example, under experimental conditions, cell surface receptors such as KIT and
      specific G protein-coupled receptors synergistically enhance FcepsilonRI-mediated
      mast cell degranulation and cytokine production. Activating mutations in critical
      signaling molecules may also contribute to such responses. In this review, we
      describe our research exploring the mechanisms regulating these synergistic
      interactions and, furthermore, discuss the relevance of our observations in the
      context of clinical considerations.

PMID- 18827982
TI  - Progenitor migration to the thymus and T cell lineage commitment.
AB  - T cells developing in the thymus are ultimately derived from bone marrow (BM)
      hematopoietic stem cells (HSCs). An understanding of the developmental steps
      between HSCs and T cells is important for gaining insight into cancers of the T
      lineage, improving T cell reconstitution after BM transplantation, and also to
      help ameliorate immunological defects in aging. In this article, we summarize our
      current understanding of the inter-related fields of early T cell development and
      thymic aging, and briefly discuss major unresolved questions in this field.

PMID- 18827983
TI  - Cbl- and Nedd4-family ubiquitin ligases: balancing tolerance and immunity.
AB  - Engagement of the T cell receptor (TCR) with its cognate peptide/MHC initiates a
      cascade of signaling events that results in T cell activation. Limiting the
      extent and duration of TCR signaling ensures a tightly constrained response,
      protecting cells from the deleterious impact of chronic activation. In order to
      limit the duration of activation, T cells must adjust levels of key signaling
      proteins. This can be accomplished by altering protein synthesis or by changing
      the rate of protein degradation. Ubiquitination is a process of 'tagging' a
      protein with ubiquitin and is one means of initiating protein degradation. This
      process is activated when an E3 ubiquitin ligase mediates the transfer of
      ubiquitin to a target protein. Accordingly, E3 ubiquitin ligases have recently
      emerged as key regulators of immune cell function. This review will explore how a
      small group of E3 ubiquitin ligases regulate T cell responses and thus direct
      adaptive immunity.

PMID- 18827984
TI  - Pharmacological analysis of recombinant NR1a/2A and NR1a/2B NMDA receptors using
      the whole-cell patch-clamp method.
AB  - N-methyl-D-aspartate receptors (NMDARs) are ligand-gated ion channels belonging
      to the family of ionotropic glutamate receptors. Functional NMDARs are
      heterotetrameric assemblies of NR1 subunits with at least one type of NR2
      subunits. Various combinations of these subunits form distinct NMDAR subtypes
      involved in a variety of physiological and pathological processes. Several
      pharmaceutical companies search subunit-selective drugs for curing various
      neurological diseases and having favorable side-effect profile. We applied the
      whole-cell patch-clamp technique for testing NR2B subunit-specific drugs in HEK
      cells transiently or stably expressing different types of NMDAR subunits. In
      stable cell lines, we applied an inducible mammalian expression system; cDNAs of
      NR1 and either NR2A or NR2B subunits were inserted into an ecdyson-inducible
      mammalian expression vector and were introduced into HEK293 cells. These
      expression systems proved to be suitable to analyze precisely the subtype
      selectivity of newly synthesized NR2B-selective NMDAR antagonists by using whole
      cell patch-clamp technique.

PMID- 18827985
TI  - Memantine as an example of a fast, voltage-dependent, open channel N-methyl-D
      aspartate receptor blocker.
AB  - Electrophysiological techniques can be used to great effect to help determine the
      mechanism of action of a compound. However, many factors can compromise the
      resulting data and their analysis, such as the speed of solution exchange,
      expression of additional ion channel populations including other ligand-gated
      receptors and voltage-gated channels, compounds having multiple binding sites,
      and current desensitization and rundown. In this chapter, such problems and their
      solutions are discussed and illustrated using data from experiments involving the
      uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist memantine.
      Memantine differs from many other NMDA receptor channel blockers in that it is
      well tolerated and does not cause psychotomimetic effects at therapeutic doses.
      Various electrophysiological parameters of NMDA-induced current blockade by
      memantine have been proposed to be important in determining therapeutic
      tolerability, potency, onset and offset kinetics, and voltage dependency. These
      were all measured using whole cell patch-clamp techniques using hippocampal
      neurons. Full results are shown here for memantine, and these are summarized and
      compared with those from similar experiments with other NMDA channel blockers.
      The interpretation of these results is discussed, as are theories concerning the
      tolerability of NMDA channel blockers, with the aim of illustrating how
      electrophysiological data can be used to form and support a physiological
      hypothesis.

PMID- 18827986
TI  - Methods for evaluation of positive allosteric modulators of glutamate AMPA
      receptors.
AB  - Hypofunctioning of glutamate synaptic transmission in the central nervous system
      (CNS) has been proposed as a factor that may contribute to cognitive deficits
      associated with various neurological and psychiatric disorders. Positive
      allosteric modulation of the alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic
      acid (AMPA) subtype of glutamate receptors has been proposed as a novel
      therapeutic approach, because these receptors mediate the majority of rapid
      excitatory neurotransmission and are intimately involved in long-term changes in
      synaptic plasticity thought to underlie mnemonic processing. By definition,
      positive allosteric modulators do not affect AMPA receptor activity alone but can
      markedly enhance ion flux through the ion channel pore in the presence of bound
      agonist. Despite this commonality, positive allosteric modulators can be
      segregated on the basis of the preferential effects on AMPA receptor subunits,
      their alternatively spliced variants and/or their biophysical mechanism of
      action. This chapter provides a detailed description of the methodologies used to
      evaluate the potency/efficacy and biophysical mechanism of action of positive
      allosteric modulators of AMPA receptors.

PMID- 18827987
TI  - Automated voltage-clamp technique.
AB  - The voltage-clamp electrophysiology method is the gold standard for measuring the
      function of ion channels. In the past, this technique has had limited
      applicability in pharmaceutical drug discovery because of its low throughput,
      steep learning curve, and challenges in standardization of the experiments.
      Recently, new electrophysiology platforms have been developed, which are based on
      the use of planar electrodes. One key advantage of the new electrode geometry is
      that it makes the process of cell-to-electrode sealing amenable to automation,
      thus increasing the throughput and significantly reducing the skill-set needed to
      run the experiments. The further addition of computer-controlled fluidics,
      voltage-clamping electronics, and automated data handling makes it possible to
      perform multiple electrophysiology experiments in parallel with a high degree of
      consistency and in completely automated mode. Among the new offerings for
      automated voltage clamp, one of the systems, PatchXpress/Sealchip, is quickly
      becoming the new gold standard for the quantification of ion channel function. In
      this chapter, we provide an overview of the new planar patch-clamping platforms
      and describe how electrophysiology experiments are performed on the
      PatchXpress/Sealchip automated system.

PMID- 18827988
TI  - Flip-the-tip: automated patch clamping based on glass electrodes.
AB  - A conventional borosilicate glass patch pipette is glued into a plastic jacket,
      forming the entity of a FlipTip. One or two three-channel modules of recording
      tip sockets are mounted on a liquid handler platform to take up FlipTips. The tip
      sockets are connected to preamplifiers (HEKA) and to a suction system. The inner
      chamber of the tip sockets is filled with intracellular solution (IS), and
      FlipTips are prefilled with extracellular solution (ES) immediately before use.
      The FlipTips are then inserted into the recording tip sockets, and suspended
      cells are taken out of a cell hotel and dispensed into the open back of the
      FlipTips. Simply by gravity, the cells move down toward the end of the pipette.
      Continuous gentle suction draws a single cell into the very end of the tip,
      forming a classical GigaSeal of 1-5GOmega. Stronger suction pulses are then
      applied to establish the open whole-cell configuration. Under voltage-clamp
      conditions, the response of an ion channel is measured simultaneously in three to
      six recording sockets. Alternatively, the perforated patch method is used with
      Amphoterecine B as the pore-forming agent. Compound delivery is accomplished with
      a fused silica quartz pipette through the open back of the FlipTip directly onto
      the cell. All these tasks are performed automatically and completely unattended
      by the Flyscreen 8500 automated patch-clamp robot. A data throughput of several
      hundred data points per day can be accomplished with the system.

PMID- 18827989
TI  - The roboocyte: automated electrophysiology based on Xenopus oocytes.
AB  - Automated electrophysiological assays are of great importance for modern drug
      discovery, and various approaches have been developed into practical devices.
      Here, we describe the automation of two-electrode voltage-clamp (TEVC) recording
      from Xenopus oocytes using the Roboocyte automated workstation, jointly developed
      by Multi Channel Systems and Bayer Technology Services. We briefly discuss the
      technology, including its advantages and limitations relative to patch clamp and
      other TEVC systems. We provide a step-by-step description of typical operating
      procedures and show that the Roboocyte represents a practical and highly
      effective way to perform automated electrophysiology in an industrial setting.

PMID- 18827990
TI  - Infrared-guided laser stimulation as a tool for elucidating the synaptic site of
      expression of long-term synaptic plasticity.
AB  - Long-term potentiation is a synaptic mechanism thought to be involved in learning
      and memory. Long-term depression (LTD), an activity-dependent decrease in
      synaptic efficacy, may be an equally important mechanism that permits neural
      networks to store information more effectively. Two forms of LTD have been
      identified in the mammalian central nervous system, which are induced by the
      synaptic activation of N-methyl-D: -aspartate (NMDA) and metabotropic glutamate
      (mGlu) receptors, respectively. Whereas the expression mechanisms of NMDA
      receptor-dependent LTD have been demonstrated to be postsynaptic, those of mGlu
      receptor-dependent LTD have not been clearly identified. In order to address this
      issue, a variety of different electrophysiological methods have been used. A very
      elegant way to realize this experimental approach is provided by the development
      of photolytic application of glutamate, which allows the temporally and spatially
      highly specific activation of any neuron or any part of the neuron. By means of
      simultaneous application of electrical and photolytic stimulation techniques, it
      has been demonstrated that mGlu receptor-induced LTD is compatible with a
      presynaptic mechanism of expression.

PMID- 18827991
TI  - Single-cell RT-PCR, a technique to decipher the electrical, anatomical, and
      genetic determinants of neuronal diversity.
AB  - The patch-clamp technique has allowed detailed studies on the electrical
      properties of neurons. Dye loading through patch pipettes has allowed
      characterizing the morphological properties of the neurons. In addition, the
      patch-clamp technique also allows harvesting mRNA from single cells to study gene
      expression at the single-cell level (known as single-cell reverse transcription
      polymerase chain reaction [RT-PCR] [1-3]). The combination of these three
      approaches allows determination of the Gene expression, Electrophysiology and
      Morphology (GEM) profile of neurons (gene expression, electrophysiology, and
      morphology) using a single patch pipette and patch-clamp recording. This
      combination provides a powerful technique to study and correlate the neuron's
      gene expression with its phenotype (electrical behavior and morphology) ( 4 - 7
      ). The harvesting and amplification of single-cell mRNA for gene expression
      studies is a challenging task, especially for researchers with sparse or no
      training in molecular biology (see Notes 1 and 2). Here, we describe in detail
      the GEM profiling approach with special attention to the gene expression
      profiling.

PMID- 18827992
TI  - Mechanosensitive ion channels investigated simultaneously by scanning probe
      microscopy and patch clamp.
AB  - Mechanosensitive ion channels play an important role for the perception of
      mechanical signals such as touch, balance, or sound. Here, a new experimental
      strategy is presented providing well-defined access to single mechanosensitive
      ion channels in living cells. As a representative example, the investigation of
      mechanosensitive transduction channels in cochlear hair cells is discussed in
      detail including all essential technical aspects. Three different techniques were
      combined: atomic force microscopy (AFM) as a device for local mechanical
      stimulation, patch clamp for recording the current response of mechanosensitive
      ion channels, and differential interference contrast (DIC) microscopy equipped
      with an upright water-immersion objective lens. A major challenge was to adapt
      the mechanical design of the AFM setup to the small working distance of the light
      microscope and the electrical design of the AFM electronics. Various protocols
      for the preparation and investigation of the organ of Corti with AFM are
      presented.

PMID- 18827993
TI  - Synaptic connectivity in engineered neuronal networks.
AB  - In this study, we have demonstrated a method to organize cells in dissociated
      cultures using engineered chemical clues on the culture surface and determined
      their connectivity patterns. Although almost all elements of the synaptic
      transmission machinery between neurons or between neurons and muscle fibers can
      be studied separately in single-cell models in dissociated cultures, the
      difficulty of clarifying the complex interactions between these elements makes
      random cultures not particularly suitable for specific studies. Factors affecting
      synaptic transmission are generally studied in organotypic cultures, brain
      slices, or in vivo where the cellular architecture generally remains intact.
      However, by utilizing engineered neuronal networks, complex phenomenon such as
      synaptic transmission can be studied in a simple, functional, cell culture-based
      system. We have utilized self-assembled monolayers (SAMs) and photolithography to
      create the surface templates. Embryonic hippocampal cells, plated on the
      resultant patterns in serum-free medium, followed the surface clues and formed
      the engineered neuronal networks. Basic electrophysiological methods were applied
      to characterize the synaptic connectivity in these engineered two-cell networks.

PMID- 18827994
TI  - Modeling of action potential generation in NG108-15 cells.
AB  - In order to explore the possibility of identifying toxins based on their effect
      on the shape of action potentials, we created a computer model of the action
      potential generation in NG108-15 cells (a neuroblastoma/glioma hybrid cell line).
      To generate the experimental data for model validation, voltage-dependent sodium,
      potassium, and high-threshold calcium currents, as well as action potentials,
      were recorded from NG108-15 cells with conventional whole-cell patch-clamp
      methods. Based on the classic Hodgkin-Huxley formalism and the linear
      thermodynamic description of the rate constants, ion channel parameters were
      estimated using an automatic fitting method. Utilizing the established
      parameters, action potentials were generated using the Hodgkin-Huxley formalism
      and were fitted to the recorded action potentials. To demonstrate the
      applicability of the method for toxin detection and discrimination, the effect of
      tetrodotoxin (a sodium channel blocker) and tefluthrin (a pyrethroid that is a
      sodium channel opener) was studied. The two toxins affected the shape of the
      action potentials differently, and their respective effects were identified based
      on the predicted changes in the fitted parameters.

PMID- 18827995
TI  - Whole-cell voltage clamp on skeletal muscle fibers with the silicone-clamp
      technique.
AB  - Control of membrane voltage and membrane current measurements are of strong
      interest for the study of numerous aspects of skeletal muscle physiology and
      pathophysiology. The silicone-clamp technique makes use of a conventional patch
      clamp apparatus to achieve whole-cell voltage clamp of a restricted portion of a
      fully differentiated adult skeletal muscle fiber. The major part of an isolated
      muscle fiber is insulated from the extracellular medium with silicone grease, and
      the tip of a single microelectrode connected to the amplifier is then inserted
      within the fiber through the silicone layer. This method represents an
      alternative to the traditional vaseline-gap isolation and two or three
      microelectrode voltage-clamp techniques. This chapter reviews the main benefits
      of the silicone-clamp technique and provides detailed insights into its practical
      implementation.

PMID- 18827996
TI  - Determination of channel properties at the unitary level in adult mammalian
      isolated cardiomyocytes.
AB  - This chapter describes methods to investigate mammalian cardiac channel
      properties at the single-channel level. Cell isolation is performed from adult
      heart by enzymatic digestion using the Langendorff apparatus. Isolation
      proceeding is suitable for rabbit, rat, and mouse hearts. Also, isolation of
      human atrial cardiomyocytes is described. In freshly isolated cells or cells
      maintained in primary culture, the single-channel variants of the patch-clamp
      technique (cell-attached, inside-out, and outside-out) are used to investigate
      channel properties. Biophysical properties such as conductance and ionic
      selectivity are determined. Also, regulations by extracellular and intracellular
      mechanisms are investigated. To illustrate the study, the author provides an
      example by the characterization of a calcium-activated nonselective cation
      channel (TRPM4).

PMID- 18827997
TI  - Electrophysiological properties of embryonic stem cells during differentiation
      into cardiomyocyte-like cell types.
AB  - The method described here to differentiate mouse embryonic stem (ES) cells into
      cardiomyocytes is adapted from Maltsev et al. and results in a high percentage of
      spontaneously beating cardiomyocyte-like cells. In order to determine to what
      extent the differentiating ES cells resemble true cardiomyocytes, the cells were
      electrophysiologically characterized during differentiation, using the whole-cell
      variant of the patch-clamp technique. Action potentials (APs) and membrane
      currents were recorded and analyzed off-line to determine electrophysiological
      changes during development.

PMID- 18827998
TI  - Hybrid neuronal network studies under dynamic clamp.
AB  - Even a complete understanding of the biophysical properties driving neuronal
      behavior would be insufficient to explain the interactions between neurons,
      neuronal assemblies, and brain regions. Exploring interactions between small
      numbers of synaptically coupled neurons in vitro can provide insight into the in
      vivo activity of neuronal assemblies. However, pairs of synaptically coupled
      neurons are notoriously difficult to find in vitro, and trying to study networks
      of more than two neurons is nearly impossible. The advent of the dynamic-clamp
      technique enables researchers to generate hybrid networks of neurons in which
      living neurons are synaptically coupled through computationally generated
      synapses. In this chapter, we provide an overview of the components of a dynamic
      clamp system. We detail how to use dynamic clamp to construct simple neuronal
      networks from living neurons as well as hybrid networks including both living and
      in silico neurons.

PMID- 18827999
TI  - Cardiac channelopathies studied with the dynamic action potential-clamp
      technique.
AB  - The cardiac long QT syndrome (LQTS) is characterized by a delayed repolarization
      of the ventricular myocytes, resulting in prolongation of the QT interval on the
      electrocardiogram and increased propensity to cardiac arrhythmias. Congenital
      LQTS has been linked to mutations in genes encoding ion channel subunits. For a
      better understanding of LQTS and associated arrhythmias, insight into the nature
      of ion channel (dys)function is indispensable. Conventionally, voltage-clamp
      analysis and subsequent mathematical modeling are used to study cardiac
      channelopathies and to link a certain genetic defect to its cellular phenotype.
      The recently introduced "dynamic action potential clamp" (dAPC) technique
      represents an alternative approach, in which a selected native ionic current of
      the ventricular myocyte can effectively be replaced with wild-type (WT) or mutant
      current recorded from a human embryonic kidney (HEK)-293 cell that is voltage
      clamped by the free-running action potential (AP) of the myocyte. Both a computed
      model of the human ventricular cell and a freshly isolated myocyte can
      effectively be used in dAPC experiments, resulting in rapid and unambiguous
      determination of the effect(s) of an ion channel mutation on the ventricular AP.
      The dAPC technique represents a promising new tool to study various cardiac ion
      channels and may also prove useful in related fields of research, for example, in
      neurophysiology.

PMID- 18828000
TI  - Principles of single-channel kinetic analysis.
AB  - Single-channel recording provides molecular insights that are nearly unattainable
      from macroscopic measurements. Analysis of the data, however, has proven to be a
      difficult challenge. Early approach relies on the half-amplitude threshold
      detection to idealize the data into dwell-times, followed by fitting of the
      duration histograms to resolve the kinetics. More recent analysis exploits
      explicit modeling of both the channel and noise statistics to improve the
      idealization accuracy. The dwell-time fitting has also evolved into direct
      fitting of the dwell-time sequences using the full maximum likelihood approach
      while taking account of the effects of missed events. Finally, hidden Markov
      modeling provides a new paradigm in which both the amplitudes and kinetics can be
      analyzed simultaneously without the need of idealization. The progress in theory,
      along with the advance in computing power and the development of user-friendly
      software, has made single-channel analysis, once a specialty task, now readily
      accessible to a broader community of scientists.

PMID- 18828001
TI  - Use of Xenopus oocytes to measure ionic selectivity of pore-forming peptides and
      ion channels.
AB  - The Xenopus laevis oocyte is a widely used system for heterologous expression of
      exogenous ion channel proteins (1, 2). Among other advantages, these easy to
      obtain, mechanically and electrically stable, large-sized cells enable multiple
      types of electrophysiological recordings: two-electrode voltage-clamp, single
      cell attached or cell-free patch-clamp, and macropatch recordings. The size of an
      oocyte (1 mm in diameter) also allows the use of additional electrodes (1-3) for
      injection of diverse materials (Ca2+ chelators, peptides, chemicals, antibodies,
      proteic-partners, and so on) before or during the course of the
      electrophysiological experiment. We have successfully used this system to analyze
      the biophysical properties of pore-forming peptides. Simple perfusion of these
      peptides induced the formation of channels in the oocyte plasma membrane; these
      channels can then be studied and characterized in diverse ionic conditions. The
      ease of the perfusion and the stability of the voltage-clamped oocyte make it a
      powerful tool for such analyses. Compared with artificial bilayers, oocytes offer
      a real animal plasma membrane where biophysical properties and toxicity can be
      studied in the same environment.

PMID- 18828002
TI  - Estimation of quantal parameters with multiple-probability fluctuation analysis.
AB  - The functional properties of central synapses are difficult to study because they
      can be modulated either presynaptically or postsynaptically, each connection has
      multiple contacts and release at each contact is stochastic. Moreover, studying
      central synapses with electrophysiology is complicated by the fact that synapses
      are often remote from the recording site and signals are often difficult to
      resolve above the noise. This together with the fact that central synapses often
      have few release sites and have nonuniform quantal parameters makes classical
      quantal analysis methods difficult to apply. Here, we discuss an alternative
      approach, multiple-probability fluctuation analysis (MPFA), which can be used to
      estimate nonuniform quantal parameters from fits of the relationship between the
      variance and mean amplitude of postsynaptic responses, recorded at different
      release probabilities. We illustrate the experimental protocols and the analysis
      procedure that should be followed to perform MPFA and interpret the estimated
      parameters.

PMID- 18828003
TI  - Triple tracks in CR-39 as the result of Pd-D Co-deposition: evidence of energetic
      neutrons.
AB  - Since the announcement by Fleischmann and Pons that the excess enthalpy generated
      in the negatively polarized Pd-D-D(2)O system was attributable to nuclear
      reactions occurring inside the Pd lattice, there have been reports of other
      manifestations of nuclear activities in this system. In particular, there have
      been reports of tritium and helium-4 production; emission of energetic particles,
      gamma or X-rays, and neutrons; as well as the transmutation of elements. In this
      communication, the results of Pd-D co-deposition experiments conducted with the
      cathode in close contact with CR-39, a solid-state nuclear etch detector, are
      reported. Among the solitary tracks due to individual energetic particles, triple
      tracks are observed. Microscopic examination of the bottom of the triple track
      pit shows that the three lobes of the track are splitting apart from a center
      point. The presence of three alpha-particle tracks outgoing from a single point
      is diagnostic of the (12)C(n,n')3alpha carbon breakup reaction and suggests that
      DT reactions that produce > or = 9.6 MeV neutrons are occurring inside the Pd
      lattice. To our knowledge, this is the first report of the production of
      energetic (> or = 9.6 MeV) neutrons in the Pd-D system.

PMID- 18828004
TI  - HbA 1c as a risk factor for heart failure in persons with diabetes: the
      Atherosclerosis Risk in Communities (ARIC) study.
AB  - AIMS/HYPOTHESIS: Heart failure (HF) incidence in diabetes in both the presence
      and absence of CHD is rising. Prospective population-based studies can help
      describe the relationship between HbA(1c), a measure of glycaemia control, and HF
      risk. METHODS: We studied the incidence of HF hospitalisation or death among
      1,827 participants in the Atherosclerosis Risk in Communities (ARIC) study with
      diabetes and no evidence of HF at baseline. Cox proportional hazard models
      included age, sex, race, education, health insurance status, alcohol consumption,
      BMI and WHR, and major CHD risk factors (BP level and medications, LDL- and HDL
      cholesterol levels, and smoking). RESULTS: In this population of persons with
      diabetes, crude HF incidence rates per 1,000 person-years were lower in the
      absence of CHD (incidence rate 15.5 for CHD-negative vs 56.4 for CHD-positive,
      p<0.001). The adjusted HR of HF for each 1% higher HbA(1c) was 1.17 (95% CI 1.11
      1.25) for the non-CHD group and 1.20 (95% CI 1.04-1.40) for the CHD group. When
      the analysis was limited to HF cases which occurred in the absence of prevalent
      or incident CHD (during follow-up) the adjusted HR remained 1.20 (95% CI 1.11
      1.29). CONCLUSIONS/INTERPRETATIONS: These data suggest HbA(1c) is an independent
      risk factor for incident HF in persons with diabetes with and without CHD. Long
      term clinical trials of tight glycaemic control should quantify the impact of
      different treatment regimens on HF risk reduction.

PMID- 18828005
TI  - Effect of an UHMWPE patellar component on stress fields in the patella: a finite
      element analysis.
AB  - An increased stress in the patella due to the implantation of a patellar button
      may also be another potential source of pain in total knee arthroplasty patients.
      This study assessed the location inside the patella having largest stress change
      after implantation of an ultra high molecular polyethylene patella button. Finite
      elements models of the patellae before and after implantation of patellar button
      were created. Experimentally determined spring constants of muscles and
      ligaments, and patellofemoral contacting loads were applied to the models at 30
      degrees , 60 degrees , and 90 degrees of knee flexion. The Von Mises stress of
      the intact patella decreased with increased knee flexion, while that of implanted
      patella increased. Also, the stress range in the implanted patella was 3-9 times
      higher than in the intact one. The highly stressed region of the intact patella
      moved proximally with higher knee flexion angles, while that of the implanted
      model stayed near the central anterior patella. At 90 degrees of knee flexion,
      the stress in the anterodistal patella increased considerably after implantation
      of a patella button so that the anterodistal patella may be susceptible to be
      painful source after the total knee replacement.

PMID- 18828006
TI  - Mercury speciation and total trace element determination of low-biomass
      biological samples.
AB  - Current approaches to mercury speciation and total trace element analysis require
      separate extraction/digestions of the sample. Ecologically important aquatic
      organisms--notably primary consumers such as zooplankton, polychaetes and
      amphipods--usually yield very low biomass for analysis, even with significant
      compositing of multiple organisms. Individual organisms in the lower aquatic food
      chains (mussels, snails, oysters, silversides, killifish) can also have very low
      sample mass, and analysis of whole single organisms is important to metal uptake
      studies. A method for the determination of both methyl Hg and total heavy metal
      concentrations (Zn, As, Se, Cd, Hg, Pb) in a single, low-mass sample of aquatic
      organisms was developed. Samples (2 to 50 mg) were spiked with enriched with
      (201)MeHg and (199)Hg, then leached in 4 M HNO(3) at 55 degrees C for extraction
      of MeHg. After 16 h, an aliquot (0.05 mL) was removed to determine mercury
      species (methyl and inorganic Hg) by isotope dilution gas chromatography
      inductively coupled plasma mass spectrometry (ICP-MS). The leachate was then
      acidified to 9 M HNO(3) and digested in a microwave at 150 degrees C for 10 min,
      and total metal concentrations were determined by collision cell ICP-MS. The
      method was validated by analyzing five biological certified reference materials.
      Average percent recoveries for Zn, As, Se, Cd, MeHg, Hg(total) and Pb were 99.9%,
      103.5%, 100.4%, 103.3%, 101%, 97.7%, and 97.1%, respectively. The correlation
      between the sum of MeHg and inorganic Hg from the speciation analysis and total
      Hg by conventional digestion of the sample was determined for a large sample set
      of aquatic invertebrates (n = 285). Excellent agreement between the two measured
      values was achieved. This method is advantageous in situations where sample size
      is limited, and where correlations between Hg species and other metals are
      required in the same sample. The method also provides further validation of
      speciation data, by corroborating the sum of the Hg species concentrations with
      the total Hg concentration.

PMID- 18828007
TI  - The outer membrane TolC is involved in cysteine tolerance and overproduction in
      Escherichia coli.
AB  - L-cysteine is an important amino acid in terms of its industrial applications. We
      previously found marked production of L-cysteine directly from glucose in
      recombinant Escherichia coli cells by the combination of enhancing biosynthetic
      activity and weakening the degradation pathway. Further improvements in L
      cysteine production are expected to use the amino acid efflux system. Here, we
      identified a novel gene involved in L-cysteine export using a systematic and
      comprehensive collection of gene-disrupted E. coli K-12 mutants (the Keio
      collection). Among the 3,985 nonessential gene mutants, tolC-disrupted cells
      showed hypersensitivity to L-cysteine relative to wild-type cells. Gene
      expression analysis revealed that the tolC gene encoding the outer membrane
      channel is essential for L-cysteine tolerance in E. coli cells. However, L
      cysteine tolerance is not mediated by TolC-dependent drug efflux systems such as
      AcrA and AcrB. It also appears that other outer membrane porins including OmpA
      and OmpF do not participate in TolC-dependent L-cysteine tolerance. When a low
      copy-number plasmid carrying the tolC gene was introduced into E. coli cells with
      enhanced biosynthesis, weakened degradation, and improved export of L-cysteine,
      the transformants exhibited more L-cysteine tolerance and production than cells
      carrying the vector only. We concluded that TolC plays an important role in L: 
      cysteine tolerance probably due to its export ability and that TolC
      overexpression is effective for L-cysteine production in E. coli.

PMID- 18828008
TI  - Plagiarism, salami slicing, and Lobachevsky.

PMID- 18828009
TI  - Xanthoma of bone associated with lipoprotein lipase deficiency.
AB  - Lipoprotein lipase (LPL) deficiency is an extremely rare congenital metabolic
      disorder with an accumulation of chylomicrons in the blood. We encountered a
      patient with an LPL deficiency leading to multiple bone xanthomas associated with
      hyperlipidemia. Radiographs and MRI of the humerus and femur revealed symmetrical
      bone lesions, and there is a possibility that these symmetrical lesions may
      therefore be a characteristic feature for this disorder.

PMID- 18828010
TI  - Combined CT and fluoroscopic guidance of balloon kyphoplasty versus fluoroscopy
      only procedures.
AB  - OBJECTIVE: To evaluate the performance of combined (computed tomography (CT) and
      fluoroscopic) guidance of balloon kyphoplasty in comparison to fluoroscopic
      guidance alone. MATERIALS AND METHODS: Forty-one kyphoplasties were performed
      between January 2005 and March 2006 according to two different protocols. Study
      group 1 consisted of 20 consecutive patients with 20 balloon kyphoplasty
      procedures under dual guidance (CT scan and fluoroscopy) for osteoporotic or
      traumatic vertebral fractures. Study group 2 consisted of 21 consecutive patients
      in whom kyphoplasty was performed with fluoroscopy alone. Visualization of the
      pedicles, the final of the balloon position, and cement distribution were
      evaluated(1-poor, 2-intermediate, 3-good). RESULTS: Combined use of CT and
      fluoroscopy (group 1) was superior in identifying the pedicles (100% versus
      66.7%, p = 0.009) and balloon placement (100% versus 71.4%, p = 0.02) but not in
      monitoring of cement distribution within the vertebral body (100% versus 90.5%, p
      = 0.49). The difference between the two groups was more pronounced in the
      thoracic spine than in the lumbar spine. CONCLUSION: CT/fluoroscopic guidance of
      kyphoplasty combines safe CT-guided insertion of the osteointroducers and
      balloons as well as fluoroscopic real-time monitoring of polymethylmethacrylate
      injection.

PMID- 18828011
TI  - Hi-tech systems for in-vivo image-guided preclinical radiobiology.

PMID- 18828012
TI  - Observer variation in FDG PET-CT for staging of non-small-cell lung carcinoma.
AB  - PURPOSE: Error and variation in reporting remains one of the weakest features of
      clinical imaging despite enormous technological advances in nuclear medicine and
      radiology. The aim of this study was to evaluate agreement amongst experienced
      readers in staging non-small-cell lung cancer (NSCLC) with PET-CT. METHODS: A
      series of (18)F-FDG PET-CT scans from 100 consecutive patients were reviewed
      independently by three experienced readers, with two readers reviewing each scan
      series a second time. Individual mediastinal lymph node stations were assessed as
      benign/inflammatory, equivocal or malignant, and AJCC N and M stage were also
      assigned. Kappa (kappa) was used to compare ratings from two categories and
      weighted kappa (kappa(w)) for three or more categories, and kappa values were
      interpreted according to the Landis-Koch benchmarks. RESULTS: Both intra- and
      interobserver agreement for N and M staging were high. For M staging there was
      almost perfect intra- and interobserver agreement (kappa = 0.90-0.93). For N
      staging, agreement was either almost perfect or substantial (intraobserver
      kappa(w) = 0.79, 0.91; interobserver kappa(w) = 0.75-0.81). Importantly, there
      was almost perfect agreement for N0/1 vs N2/3 disease (kappa = 0.80-0.97).
      Agreement for inferior and superior mediastinal nodes (stations 1, 2, 3, 7, 8, 9)
      was either almost perfect or substantial (kappa(w) = 0.71-0.88), but lower for
      hilar nodes (10; kappa(w) = 0.56-0.71). Interreporter variability was greatest
      for aortopulmonary nodes (5, 6; kappa(w) = 0.48-0.55). CONCLUSION: Amongst
      experienced reporters in a single centre, there was a very high level of
      agreement for both mediastinal nodal stage and detection of distant metastases
      with PET-CT. This supports the use of PET-CT as a robust imaging modality for
      staging NSCLC.

PMID- 18828013
TI  - Longitudinal assessment of cerebral 5-HT2A receptors in healthy elderly
      volunteers: an [18F]-altanserin PET study.
AB  - PURPOSE: The serotonin 2A (5-HT(2A)) receptor is of interest in several
      psychiatric and neurological diseases. In the present study we investigated the
      longitudinal stability of 5-HT(2A) receptors and the stability of the
      quantification procedure in the elderly in order to be able to study elderly
      patients with neuropsychiatric diseases on a longitudinal basis. METHODS: [(18)F]
      Altanserin PET was used to quantify 5-HT(2A) receptors in 12 healthy elderly
      individuals at baseline and at 2 years in six volumes of interest. A
      bolus/infusion protocol was used to achieve the binding potential, BP(P). The
      reproducibility as assessed in terms of variability and the reliability as
      assessed in terms of intraclass correlation coefficient (ICC) were used to
      compare inter- and intraobserver stability and to evaluate the effects of
      increasing complexity of partial volume (PV) corrections. We also compared the
      stability of our measurements over 2 years with the stability of data from an
      earlier study with 2-week test-retest measurements. RESULTS: BP(P) was unaltered
      at follow-up without the use of PV correction and when applying two-tissue PV
      correction, test-retest reproducibility was 12-15% and reliability 0.45-0.67 in
      the large bilateral regions such as the parietal, temporal, occipital and frontal
      cortices, while orbitofrontal and anterior cingulate cortical regions were less
      stable. The use of PV correction decreased the variability but also decreased the
      between-subject variation, thereby worsening the reliability. CONCLUSION: In
      healthy elderly individuals, brain 5-HT(2A) receptor binding remains stable over
      2 years, and acceptable reproducibility and reliability in larger regions and
      high intra- and interobserver stability allow the use of [(18)F]-altanserin in
      longitudinal studies of patients with neuropsychiatric disorders.

PMID- 18828014
TI  - Thyroid uptake of 67Ga-citrate is associated with thyroid autoimmunity and
      hypothyroidism in patients with sarcoidosis.
AB  - PURPOSE: To evaluate the association of gallium-67 ((67)Ga)-citrate thyroid
      uptake with the presence of thyroid disorders in patients with sarcoidosis (S
      patients). METHODS: Eighty-four S patients were evaluated by a complete thyroid
      work-up (neck ultrasound, circulating thyroid hormones and anti-thyroid
      antibodies, fine-needle aspiration). RESULTS: In S patients with (67)Ga thyroid
      uptake (respect those without): serum thyroid-stimulating hormone, the titre of
      anti-thyroid peroxidase (AbTPO) and/or anti-thyroglobulin antibodies (AbTg), and
      the prevalence of S patients with hypothyroidism or with positive AbTg or AbTPO
      was significantly higher; a thyroid hypoechoic pattern was more frequent. The
      prevalence of thyroid nodules was not significantly different between the two
      groups. Two cases of papillary thyroid cancer were observed in S patients without
      (67)Ga thyroid uptake, whilst no case in those with (67)Ga thyroid uptake.
      CONCLUSIONS: (67)Ga thyroid uptake is associated with the presence of aggressive
      autoimmune thyroiditis and hypothyroidism in S patients; thyroid function and
      ultrasonography should be performed in the presence of (67)Ga thyroid uptake.

PMID- 18828015
TI  - Nuclear imaging of neuroinflammation: a comprehensive review of [11C]PK11195
      challengers.
AB  - Neurodegenerative, inflammatory and neoplastic brain disorders involve
      neuroinflammatory reactions, and a biomarker of neuroinflammation would be useful
      for diagnostic, drug development and therapy control of these frequent diseases.
      In vivo imaging can document the expression of the peripheral benzodiazepine
      receptor (PBR)/translocator protein 18 kDa (TSPO) that is linked to microglial
      activation and considered a hallmark of neuroinflammation. The prototype positron
      emission tomography tracer for PBR, [(11)C]PK11195, has shown limitations that
      until now have slowed the clinical applications of PBR imaging. In recent years,
      dozens of new PET and SPECT radioligands for the PBR have been radiolabelled, and
      several have been evaluated in imaging protocols. Here we review the new PBR
      ligands proposed as challengers of [(11)C]PK11195, critically analyze preclinical
      imaging studies and discuss their potential as neuroinflammation imaging agents.

PMID- 18828016
TI  - Effect of invariant chain on major histocompatibility complex class I molecule
      expression and stability on human breast tumor cell lines.
AB  - Invariant chain (Ii) binds to the human leukocyte antigen (HLA) class II molecule
      and assists it in the process of peptide acquisition. In addition, Ii binds to
      the HLA class I molecule, although there has been little study of its effects on
      the HLA class I molecule. In addition to its normal expression on antigen
      presenting cells, Ii expression is up regulated in a variety of tumors. By flow
      cytometric analysis, we found that expression of Ii resulted in an increase in
      the number of cell surface HLA class I molecules and in the proportion of
      unstable HLA class I molecules at the surface of breast tumor cell lines. These
      data suggest that the expression of Ii by tumor cells may quantitatively and
      qualitatively alter the presentation of antigens on those cells.

PMID- 18828017
TI  - Regulation of arginase I activity and expression by both PD-1 and CTLA-4 on the
      myeloid-derived suppressor cells.
AB  - An elevated number of Gr-1(+)CD11b(+) myeloid-derived suppression cells (MDSCs)
      has been described in mice and human bearing tumor and associated with immune
      suppression. Arginase I production by MDSCs in the tumor environment may be a
      central mechanism for immunosuppression and tumor evasion. In this study and
      before, we found that Gr-1(+)CD11b(+) MDSCs from ascites and spleen of mice
      bearing ovarian 18D carcinoma express a high level of PD-1, CTLA-4, B7-H1 and
      CD80 while other co-stimulatory molecules, namely CD40, B7-DC and CD86 are not
      detected. Further studies showed that PD-1 and CTLA-4 on the Gr-1(+)CD11b(+)
      MDSCs regulated the activity and expression of arginase I. The blockage and
      silencing of PD-1, CTLA-4 or both PD-1 and CTLA4 molecules could significantly
      reduce arginase I activity and expression induced with tumor-associated factor.
      Similar results were also observed while their ligands B7-H1 and/or CD80 were
      blocked or silenced. Furthermore, CD80 deficiency also decreased the arginase I
      expression and activity. Antibody blockade or silencing of PD-1, CTLA-4 or both
      reduced the suppressive potential of PD-1+CTLA-4+MDSCs. Blockade of PD-1, CTLA-4
      or both also slowed tumor growth and improved the survival rate of tumor-bearing
      mice. Thus, there may exist a coinhibitory and costimulatory molecules-based
      immuno-regulating net among MDSCs.

PMID- 18828018
TI  - The immunodominant HLA-A2-restricted MART-1 epitope is not presented on the
      surface of many melanoma cell lines.
AB  - Among the relatively large number of known tumor-associated antigens (TAA) which
      are recognized by human CD8 T-cells, Melan-A/MART-1 is one of the most-if not the
      most-frequently used target for anti-cancer vaccines in HLA-A2 + melanoma
      patients. In this study, we analyzed the killing of a large panel of melanoma
      cells by a high avidity, MART-1-specific T-cell clone or a MART-1-specific,
      polyclonal T-cell culture. Strikingly, we observed that the MART-1-specific T
      cells only killed around half of the analyzed melanoma cell lines. In contrast a
      Bcl-2-specific T-cell clone killed all melanoma cell lines, although the T-cell
      avidity of this clone was significantly lower. The MART-1-specific T-cell clone
      expressed NKG-2D and was fully capable of releasing both perforin and Granzyme B.
      Notably, the resistance to killing by the MART-1-specific T-cells could be
      overcome by pulsing of the melanoma cells with the MART-1 epitope. Thus, the very
      frequently used MART-1 epitope was not expressed on the surface of many melanoma
      cell lines. Our data emphasize that the selected tumor antigens and/or epitopes
      are critical for the outcome of anti-cancer immunotherapy.

PMID- 18828019
TI  - Diverse cross-resistance phenotype to ET-743 and PM00104 in multi-drug resistant
      cell lines.
AB  - PURPOSE: ET-743 (Yondelis, trabectedin) and PM00104 (Zalypsis) are marine derived
      compounds which demonstrate anti-tumor activity. The present study was performed
      to elucidate the relationship between the expression of ABCB1/MDR1 and ABCC1/MRP1
      with resistance to either ET-743 or PM00104. METHODS: We evaluate the association
      between expression of Pgp1, MRP1, and BCRP proteins and ET-743 or PM00104
      resistance in a large panel of multi-drug resistant cell lines derived from
      histologically unrelated human tumors that were selected with paclitaxel,
      doxorubicin, cisplatin, mitoxantrane, or gemcitibine. RESULTS: Paclitaxel
      selected resistant cell lines expressed high levels of ABCB1 (but not ABCC1 or
      ABCG2/BCRP) did not demonstrate cross-resistance to either ET-743 or PM00104. In
      contrast, the doxorubicin selected resistant cell lines also expressed high level
      of ABCB1 (but not ABCC1 or ABCG2) but did demonstrate significant cross
      resistance to both ET-743 and PM00104. The paclitaxel selected cell lines
      demonstrated cross-resistance to doxorubicin, vincristine, and mitoxantrane,
      while most of the above doxorubicin selected cell lines demonstrated cross
      resistance to paclitaxel and vincristine, but not to mitoxantrane. On the
      contrary, cisplatin and gemcitabine selected cell lines demonstrated no cross
      resistance to paclitaxel, doxorubicin, ET-743, or PM00104. siRNA down-regulation
      of ABCB1 expression in doxorubicin selected cell lines caused partial
      sensitization to both doxorubicin and paclitaxel but not to either ET-743 or
      PM00104. CONCLUSIONS: These results indicate that cell lines selected for
      resistance to either paclitaxel or doxorubicin are cross-resistant to many other
      drugs and that, for these cell lines, ABCB1 over-expression is not necessary to
      confer resistance to either ET-743 or PM00104. Diversity of cross-resistance
      observed in these multi-drug resistant cell lines are associated with the initial
      drug used for in vitro selection, but not to ABCB1 expression. This study
      suggests that a common molecular pathway other than ABCB1 may be involved in the
      mechanism of resistance to ET-743 or PM00104.

PMID- 18828020
TI  - Phase II trial of S-1 and concurrent radiotherapy in patients with locally
      advanced pancreatic cancer.
AB  - PURPOSE: S-1 has a favorable effect in unresectable pancreatic cancer and a
      potential radiosensitizer. In addition, daily oral administration of S-1 is more
      convenient than continuous infusion of 5-fluorouracil. This study was designed to
      evaluate the efficacy and safety of S-1 and concurrent radiotherapy in patients
      with locally advanced pancreatic cancer. METHODS: Eligibility criteria were
      histologically proven pancreatic adenocarcinoma, locally advanced disease, and no
      previous treatment. S-1 was administered orally at a dose of 40 mg/m(2) twice
      daily from day 1 to 14 and from day 22 to 35, and concurrent radiotherapy (a
      total dose of 50.4 Gy) was delivered in 28 fractions. One month after treatment
      completion, tumor response was evaluated by computed tomography (CT). RESULTS: A
      total of 25 patients were evaluable for efficacy and toxicity on the basis of the
      intention-to-treat analysis. The response rate and disease control rate were 24.0
      and 68.0%, respectively. There was no treatment-related death or grade 4
      toxicity. The most common grade 3 hematologic and non-hematologic toxicities were
      thrombocytopenia (4.0%) and anorexia (20%), respectively. All toxicities were
      tolerable and transient. The median time-to-progression and median overall
      survival were 6.5 months (95% confidence interval, 4.1-9.0 months) and 12.9
      months (95% confidence interval, 6.7-19.0 months), respectively, and the 1-year
      survival rate was estimated to be 43%. CONCLUSIONS: S-1 and concurrent
      radiotherapy shows favorable efficacy for disease control against locally
      advanced pancreatic cancer and was well tolerated with no severe toxicities.

PMID- 18828021
TI  - Risk factors of Pneumocystis jeroveci pneumonia in patients with systemic lupus
      erythematosus.
AB  - Pneumocystis jeroveci pneumonia (PCP) is an opportunistic infection which occurs
      mostly in the immune-deficiency host. Although PCP infected systemic lupus
      erythematosus (SLE) patient carries poor outcome, no standard guideline for
      prevention has been established. The aim of our study is to identify the risk
      factors which will indicate the PCP prophylaxis in SLE. This is a case control
      study. A search of Ramathibodi hospital's medical records between January 1994
      and March 2004, demonstrates 15 cases of SLE with PCP infection. Clinical and
      laboratory data of these patients were compared to those of 60 matched patients
      suffering from SLE but no PCP infection. Compared to SLE without PCP, those with
      PCP infection have significantly higher activity index by MEX-SLEDAI (13.6 +/-
      5.83 vs. 6.73 +/- 3.22) or more renal involvement (86 vs. 11.6%, P < 0.01),
      higher mean cumulative dose of steroid (49 +/- 29 vs. 20 +/- 8 mg/d, P < 0.01),
      but lower lymphocyte count (520 +/- 226 vs. 1420 +/- 382 cells/mm(3), P < 0.01).
      Interestingly, in all cases, a marked reduction in lymphocyte count (710 +/- 377
      cells/mm(3)) is observed before the onset of PCP infection. The estimated CD4+
      count is also found to be lower in the PCP group (156 +/- 5 vs. 276 +/- 8
      cells/mm(3)). Our study revealed that PCP infected SLE patients had higher
      disease activity, higher dose of prednisolone treatment, more likelihood of renal
      involvement, and lower lymphocyte count as well as lower CD4+ count than those
      with no PCP infection. These data should be helpful in selecting SLE patients who
      need PCP prophylaxis.

PMID- 18828022
TI  - Wegener's granulomatosis presenting as multiple bilateral renal masses: case
      report and literature review.
AB  - Wegener's granulomatosis (WG) is a disease of unknown etiology characterized by
      necrotizing granulomatous vascularitis. The upper and lower respiratory tract and
      kidney involvements are very common; however, its presentation as bilateral renal
      masses is unusual. We report a case of a 59-year-old female patient who presented
      with multiple bilateral renal masses. The patient presented with sinusal and
      ocular symptoms suggestive of WG, and positive antineutrophil cytoplasmic
      antibodies (c-ANCA) with an anti-PR3 pattern. Histopathologic examination of the
      renal biopsy specimen revealed granulomatous inflammation with vasculitis and
      fibrinoid necrosis. The patient management, including prednisone and
      cyclophosphamid, induced a marked improvement of the renal masses. This case
      illustrates that WG should be considered in the differential diagnosis of renal
      masses.

PMID- 18828023
TI  - Immunoscreening of urinary bladder cancer cDNA library and identification of
      potential tumor antigen.
AB  - OBJECTIVE: To identify potential tumor antigen by immunoscreening the urinary
      bladder cancer cDNA library with monoclonal antibodies. METHODS: Monoclonal
      antibodies were prepared. A cDNA expression library was constructed from bladder
      cancer cell line BLZ211. Immunogenic proteins were identified by immunoscreening
      the cDNA library with ten monoclonal antibodies. RESULTS: The cDNA library of
      BLZ211 cells was established using lambdaZAP as vector. The titer of unamplified
      cDNA library was 1.39x10(6) pfu/ml with a recombinant rate of 97.72%, and titer
      of amplified one was 8.4x10(9) pfu/ml. After immunoscreening, ten positive clones
      representing ten different antigens were identified, which include two proteins
      with unknown function; coactosin-like 1, eukaryotic translation elongation
      factor, HNRPA1, histidine triad nucleotide binding protein, KRT7, LCN2, TSTA3,
      zinc finger protein, C11orf48 and HSPC148. CONCLUSION: The cDNA library was of
      high quality and can be used in further study. By immunoscreening the bladder
      cancer cDNA library with ten monoclonal antibodies, we identified ten immunogenic
      proteins that otherwise would not have been identified as potential diagnostic
      marker and vaccinogens of bladder cancer using the gene discovery effort.

PMID- 18828024
TI  - Malignant glioblastomatous transformation of a low-grade glioma in a child.
AB  - BACKGROUND: The term of low-grade glioma addresses a favorable clinical outcome
      with indolent histological features in general consideration; however, recent
      studies underline the inconsistency, which originates from the accumulation of
      different histologic subtypes in this terminology. The malignant transformation
      of a low-grade glioma is unusual but presents a poor prognosis. CASE HISTORY: We
      report a case of a 12-year-old boy, who was referred for complaints of recurrent
      seizures. His physical examination was unremarkable, but it was learned that a
      peripheral mass lesion located on the left posterior parietal lobe--which had
      been thought to be a low-grade glioma--had been detected on a magnetic resonance
      imaging 2 years ago at a different hospital. The patient was then treated with
      valproate and carbamazepine for the seizures and advised to be followed up
      without any additional diagnostic and therapeutic studies for his suspected low
      grade glioma. A recent magnetic resonance imaging study showed enlargements of
      the mass and surrounding edema with additional necrosis. Surgical excision of the
      tumor was performed. After the diagnosis of glioblastoma multiforme, the patient
      received radiation therapy and chemotherapy with a good clinical recovery without
      any evidence of residue or recurrence at 12-month follow-up. CONCLUSION: The
      first line treatment modality in the management of low-grade glioma--especially
      in suitable patients--is clearly surgery. The gross total resection guarantees
      the distinguishing of the histological types of the low-grade gliomas and
      reflects the biologic behavior of these tumors. Observation without surgery must
      be reserved for selected inoperable cases.

PMID- 18828025
TI  - Lung hydatic cysts in children: comparison study between giant and non-giant
      cysts.
AB  - PURPOSE: The aim of this study is to review our experience in pediatric giant
      pulmonary hydatid cysts focusing on clinical symptoms, location of the cyst, type
      of the intervention, postoperative complications and long-term results. METHODS:
      Between June 2002 and May 2007, 118 children were operated on for hydatid lung
      cysts. Two groups were defined: Group 1, 32 children with giant hydatid cysts and
      Group 2, 86 children with non-giant cysts. The statistical significance between
      the groups was estimated using paired samples t test. RESULTS: The mean age was
      11.8 years in G1 and 9.7 years in G2. All of the patients were symptomatic in G1
      but only 18% in G2 (P=0.003). The right lower lobe was most frequently involved
      in both G1 and G2. Surgical parenchymal resection was performed in five patients
      in G1 (16%) and in 2% in G2 (P=0.033). Postoperative complications in G1 were
      more significant comparatively to G2 (P=0.003). CONCLUSION: Giant hydatid lung
      cysts represent a distinct pathology. They affect essentially adolescents and may
      reach a large size causing parenchymal destruction. Thus, surgical resections are
      frequently used and postoperative complications rate is high.

PMID- 18828026
TI  - Parenteral fish oil as monotherapy for patients with parenteral nutrition
      associated liver disease.

PMID- 18828027
TI  - A computational simulated control system for a high-force pneumatic muscle
      actuator: system definition and application as an augmented orthosis.
AB  - High-force pneumatic muscle actuators (PMAs) are used for force assistance with
      minimal displacement applications. However, poor control due to dynamic
      nonlinearities has limited PMA applications. A simulated control system is
      developed consisting of: (1) a controller relating an input position angle to an
      output proportional pressure regulator voltage, (2) a phenomenological model of
      the PMA with an internal dynamic force loop (system time constant information),
      (3) a physical model of a human sit-to-stand task and (4) an external position
      angle feed-back loop. The results indicate that PMA assistance regarding the
      human sit-to-stand task is feasible within a specified PMA operational pressure
      range.

PMID- 18828028
TI  - Muscle forces during running predicted by gradient-based and random search static
      optimisation algorithms.
AB  - Muscle forces during locomotion are often predicted using static optimisation and
      SQP. SQP has been criticised for over-estimating force magnitudes and under
      estimating co-contraction. These problems may be related to SQP's difficulty in
      locating the global minimum to complex optimisation problems. Algorithms designed
      to locate the global minimum may be useful in addressing these problems. Muscle
      forces for 18 flexors and extensors of the lower extremity were predicted for 10
      subjects during the stance phase of running. Static optimisation using SQP and
      two random search (RS) algorithms (a genetic algorithm and simulated annealing)
      estimated muscle forces by minimising the sum of cubed muscle stresses. The RS
      algorithms predicted smaller peak forces (42% smaller on average) and smaller
      muscle impulses (46% smaller on average) than SQP, and located solutions with
      smaller cost function scores. Results suggest that RS may be a more effective
      tool than SQP for minimising the sum of cubed muscle stresses in static
      optimisation.

PMID- 18828029
TI  - Estimating changes in hydration status from changes in body mass: considerations
      regarding metabolic water and glycogen storage.
AB  - The potential for imprecision in the estimation of hydration status from changes
      in body mass has been outlined previously but the equations derived from these
      derivations appear inconsistent. Reconciliation of body mass loss in terms of
      sweat loss and effective body water loss is possible from specific equation sets
      provided that gains and losses of both body mass and water used in the derivation
      of sweat loss and to derive effective body water loss are in inclusive equation
      sets. This is obligatory so that mass and water changes as quantifiable
      determinants are consistent with both internal processes and external gains and
      losses. Thus, body mass loss, substrate oxidation, metabolic water, and all the
      terms used in simultaneous equation sets have to be reconciled not only as
      identical variables but mathematically balance exactly. The revised equation for
      effective body water loss given here is different from that originally proposed.
      Metabolic water is part of body mass loss corrected for substrate oxidation,
      fluid ingestion, and respiratory water to derive sweat loss and it may not be
      justified to also include water associated with glycogen as releasable bound
      water. Accordingly, our calculated effective body water loss is substantially a
      greater loss than originally supposed but clearly still less than the simple
      balance between mass loss and fluid ingested.

PMID- 18828030
TI  - One-year endurance training: effects on lung function and airway inflammation.
AB  - The aim of this study was to determine whether endurance training in athletes
      induces airway inflammation and pulmonary function disorders. Respiratory pattern
      and function were analysed in ten healthy endurance runners at rest, during sub
      maximal exercise, and during the recovery. Inflammatory cells and metabolites
      (histamine, interleukin-8, and leukotriene E(4)) were measured in sputum at rest
      and after exercise. The experiments were conducted on three different occasions
      (basic endurance training, pre-competitive and competitive periods). In spite of
      the absence of post-exercise spirometric changes and respiratory symptoms, airway
      cells counts and inflammatory markers changed significantly. At the beginning of
      the experiment, athletes' induced sputum showed an abundance of macrophages
      compared with neutrophils. We found a high percentage of neutrophils during the
      pre-competitive and competitive periods of the sport season (41% and 37%), a
      significant increase in macrophage counts during the pre-competitive period
      (51%), and a significant rise in total cells, interleukin-8, leukotriene E(4),
      and histamine during the competitive period. In conclusion, one year's training
      increased markers of inflammation in the airways of endurance runners without
      symptoms or changes in pulmonary function, suggesting that airway inflammation is
      of insufficient magnitude to markedly impact lung function in healthy athletes.

PMID- 18828031
TI  - An eye for a worm: lateralisation of feeding behaviour in aquatic anamniotes.
AB  - Some animals, notably birds, preferentially approach and capture food items in
      their right visual field. However, this lateralised behaviour has not been
      studied extensively in anamniotes. Here we test eye preference during feeding for
      a fish, (Perccottus glenii; Teleostei, Perciformes), a newt, (Pleurodeles walti;
      Amphibia, Caudata), and a frog, (Xenopus laevis; Amphibia, Anura) using a test
      chamber that assesses reaction to visual stimuli while blocking olfactory and
      mechanical input. Both the fish and the newt showed right preferences in
      reactions to food items, but the frog did not. Our data extend our knowledge of
      the lateralised behaviours of vertebrates and are the first record of lateralised
      prey capture in a caudate amphibian. This finding dates back the history of the
      common pattern for visual lateralisation in vertebrates to Devonian, when the
      fish and quadruped lineages diverged.

PMID- 18828032
TI  - Assessing the wish to die: a 30-year review of the suicide intent scale.
AB  - This analysis drew from decades of published research to evaluate the Suicide
      Intent Scale (SIS), the dominant research tool for assessing intent to die in
      apparent suicide attempts. The review sought to 1) synthesize findings related to
      the scale's normative scores, reliability, and validity (factorial, convergent,
      and predictive), and 2) examine the objective and subjective subscales'
      performance. A literature search yielded 158 studies reporting findings for the
      SIS. Psychometric properties were summarized. Studies supported the scale's
      reliability, especially that of the subscale assessing self-reported (versus
      circumstantial indicators) of intent. Mixed findings emerged regarding convergent
      and predictive validity. The review identified shortcomings in factorial validity
      and the subscales' performance, especially for adolescents. The Suicide Intent
      Scale has some strengths, but the weaknesses require further investigation into
      how to better measure intent to die in attempted suicide.

PMID- 18828033
TI  - The role of endogenous opioids in the pathophysiology of self-injurious and
      suicidal behavior.
AB  - Multiple lines of evidence suggest that endogenous opioids are involved in the
      pathogenesis of non-suicidal self-injury (NSSI). Evidence for such a role is
      based on the partial success of opioid antagonist treatment to ameliorate NSSI,
      reports of altered pain sensitivity during episodes of NSSI, and findings of
      altered endogenous opioid levels in individuals with NSSI. While suicidal
      behavior (SB) and NSSI are distinct behaviors, NSSI is a significant risk factor
      for suicide attempts and suicide. The high co-occurrence of SB and NSSI suggests
      that they may share a common biology. Available data indicate that endogenous
      opioids may be involved in the pathophysiology of SB. Future studies of the role
      of opioids in the biological mechanisms of NSSI and SB are merited and may lead
      to the development of new treatment modalities.

PMID- 18828034
TI  - An investigation of interpersonal-psychological variables in air force suicides:
      a controlled-comparison study.
AB  - Joiner's (2005) theory attributes suicide to an individual's acquired capability
      to enact self-harm, perceived burdensomeness, and thwarted belongingness. This
      study evaluated whether Joiner's theory could differentiate United States (US)
      Air Force (AF) personnel (n = 60) who died by suicide from a living active duty
      AF personnel comparison sample (n = 122). Responses from AF personnel on several
      scales assessing Joiner's constructs were compared to data from a random sample
      of postmortem investigatory files of AF personnel who died by suicide between
      1996-2006. This research also introduced a newly designed measure, the
      Interpersonal-Psychological Survey (IPS), designed to assess the three components
      of Joiner's theory in one, easy-to-administer instrument. Analyses of the
      psychometric properties of the IPS support initial validation efforts to
      establish this scale as a predictive measure for suicide. Findings support that
      one's score on the Acquired Capability to Commit Suicide subscale of the IPS and
      the IPS overall score reliably distinguished between the two groups. The
      implications of these findings in relation to suicide prevention efforts in the
      US military are discussed.

PMID- 18828035
TI  - No association of COMT Val158Met polymorphism with suicidal behavior or CSF
      monoamine metabolites in mood disorders.
AB  - The Met allele of the Catechol-O-Methyltransferase (COMT) gene functional
      polymorphism (COMT-V158M) is associated with lower enzymatic activity than the
      Val allele and is reported to be associated with aggression, depression, and
      suicidal behavior. Since depression and impulsive-aggressive behavior may mediate
      risk for suicidal behavior, we assessed the association of this polymorphism with
      suicidal behavior. Clinical (impulsive aggression) and biological (CSF monoamine
      metabolites) endophenotypes were tested as potential mediators of the effect of
      genotype on suicide risk. Subjects with mood disorders (N = 486) and healthy
      volunteers (N = 119), all European Caucasian, were genotyped for COMT-V158M and
      assessed for DSM IV diagnoses, lifetime suicidal behavior, lifetime impulsivity,
      hostility, and aggression. CSF monoamine metabolites were assayed in a sub-sample
      of mood disorder patients (N = 111). We found no association between genotype and
      mood disorder diagnosis or with reported history of suicide attempt in mood
      disorder subjects. There was no association between genotype and lethality or
      method of suicide attempt, or with aggressive/impulsive traits. Further, there
      was no difference in monoamine metabolites by genotype. The COMT-V158M
      polymorphism was not associated with suicidal behavior in a Caucasian sample of
      mood disorder subjects, or with possible clinical or biological endophenotypes.

PMID- 18828036
TI  - A preliminary investigation of suicidality in psychiatrically hospitalized
      veterans with traumatic brain injury.
AB  - The objective of this study was to explore suicidal behaviors documented at time
      of discharge from acute psychiatric hospitalization. Data from 114 acute
      psychiatric admissions were reviewed for 22 veterans with a history of traumatic
      brain injury (TBI). Information extracted included presence of suicidal ideation,
      nature of suicide attempts, and TBI characteristics. The Lethality of Suicide
      Attempt Rating Scale was used to classify veterans' non-lethal self-harm
      behavior. Post-TBI, 6 patients (27.3%) made a total of 14 suicide attempts. Half
      of those attempts required wounds being sutured, stomach lavage, or other medical
      attention. Clinicians and researchers are strongly encouraged to focus increased
      attention on suicide prevention in those with a history of TBI.

PMID- 18828037
TI  - Suicidal thoughts among medical residents with burnout.
AB  - OBJECTIVES: Recent research showed that medical residents have a high risk for
      developing burnout. The present study investigates the prevalence of burnout and
      its relationship with suicidal thoughts among medical residents. METHODS: All
      Dutch medical residents (n = 5126) received a self-report questionnaire. Burnout
      was measured with the Maslach Burnout Inventory. Residents were asked about the
      frequency of suicidal thoughts. RESULTS: Response rate was 41.3% (n = 2115). 432
      Residents (20.6%) were classified as burnout. 12% reported having suicidal
      thoughts at least 1 time during their residency, and 1% many times. Suicidal
      thoughts were substantially more prevalent in the group with burnout in
      comparison to non-burnout (20.5% vs. 7.6%; chi(2) = 182.9, p < .001). CONCLUSION:
      Knowledge about the relationship between burnout and suicidal thoughts among
      these young medical professionals could be important for suicide prevention.

PMID- 18828038
TI  - Long-term suicide risk in schizophrenia spectrum psychoses: survival analysis by
      gender.
AB  - Patients with schizophrenia spectrum psychoses have a high risk of suicide.
      Suicide is more frequent in men. Our objective in this study was to investigate
      the long term suicide risk in schizophrenia spectrum psychoses in relation to
      gender. A cohort from 1973 to 1987 of 385 schizophrenia spectrum psychoses
      inpatients in Stockholm were followed up for cause of death in 2006. Twenty-six
      suicides (6.8%) occurred during the follow up of 24.4 years. There was no
      significant difference in suicide mortality between men (6.5%) and women (6.9%).
      There was no gender difference in death from other causes. These results indicate
      that patients with schizophrenia spectrum psychoses have a high long term suicide
      risk in both men and women. The high suicide risk in female patients deserves
      further research attention.

PMID- 18828039
TI  - The interpersonal nature of suicide: a qualitative investigation of suicide
      notes.
AB  - Prior investigations of suicide notes typically focus on verifying psychological
      theories about suicide motives. Fewer concern the interpersonal nature of
      suicide. This research investigated broad interpersonal themes related to suicide
      as revealed through suicide notes. This study was a qualitative investigation of
      suicide notes written by 138 individuals who completed suicide. Grounded theory
      analysis revealed seven interpersonal themes: 1) instructions; 2) positive
      relationships; 3) explanations; 4) relationship reconciliation/maintenance; 5)
      concern for others; 6) negative relationships; and 7) acknowledging end of
      relationship. These themes suggest that suicidal individuals consider positive
      and negative aspects of relationships in their notes, and they attempt to
      maintain and reconcile relationships even in the face of death.

PMID- 18828040
TI  - Increased use of medicinal drugs in self-harm in urban areas in Sri Lanka.
AB  - Previous research has identified pesticides as the commonest substance used in
      poisoning in Sri Lanka. The aim of the study is to describe substances used in
      overdose and the characteristics of patients admitted with medicinal drug
      overdose in an urban tertiary care hospital in Colombo. A descriptive study of
      one hundred and ninety one patients admitted with intentional self poisoning to
      National Hospital of Sri Lanka, Colombo was carried out. Medicinal drugs were the
      commonest substance used in overdose (68%). Those who used medicinal drugs were
      mainly female (72.3%) and were aged between 15-24 years (76.2%). In Colombo
      medicinal drugs were the commonest substance used in intentional self poisoning
      in contrast to findings in rural areas.

PMID- 18828045
TI  - Recognition of affective speech prosody and facial affect in deaf children with
      unilateral right cochlear implants.
AB  - Cochlear implant (CI) devices provide the opportunity for children who are deaf
      to perceive sound by electrical stimulation of the auditory nerve, with the goal
      of optimizing oral communication. One part of oral communication concerns
      meaning, while another part concerns emotion: affective speech prosody, in the
      auditory domain, and facial affect, in the visual domain. It is not known whether
      childhood CI users can identify emotion in speech and faces, so we investigated
      speech prosody and facial affect in children who had been deaf from infancy and
      experienced CI users. METHOD: Study participants were 18 CI users (ages 7-13
      years) who received right unilateral CIs and 18 age- and gender-matched controls.
      Emotion recognition in speech prosody and faces was measured by the Diagnostic
      Analysis of Nonverbal Accuracy. RESULTS: Compared to controls, children with
      right CIs could identify facial affect but not affective speech prosody. Age at
      test and time since CI activation were uncorrelated with overall outcome
      measures. CONCLUSION: Children with right CIs recognize emotion in faces but have
      limited perception of affective speech prosody.

PMID- 18828044
TI  - On approaches to the functional restoration of salivary glands damaged by
      radiation therapy for head and neck cancer, with a review of related aspects of
      salivary gland morphology and development.
AB  - Radiation therapy for cancer of the head and neck can devastate the salivary
      glands and partially devitalize the mandible and maxilla. As a result, saliva
      production is drastically reduced and its quality adversely altered. Without
      diligent home and professional care, the teeth are subject to rapid destruction
      by caries, necessitating extractions with attendant high risk of necrosis of the
      supporting bone. Innovative techniques in delivery of radiation therapy and
      administration of drugs that selectively protect normal tissues can reduce
      significantly the radiation effects on salivary glands. Nonetheless, many
      patients still suffer severe oral dryness. I review here the functional
      morphology and development of salivary glands as these relate to approaches to
      preventing and restoring radiation-induced loss of salivary function. The acinar
      cells are responsible for most of the fluid and organic material in saliva, while
      the larger ducts influence the inorganic content. A central theme of this review
      is the extent to which the several types of epithelial cells in salivary glands
      may be pluripotential and the circumstances that may influence their ability to
      replace cells that have been lost or functionally inactivated due to the effects
      of radiation. The evidence suggests that the highly differentiated cells of the
      acini and large ducts of mature glands can replace themselves except when the
      respective pools of available cells are greatly diminished via apoptosis or
      necrosis owing to severely stressful events. Under the latter circumstances,
      relatively undifferentiated cells in the intercalated ducts proliferate and
      redifferentiate as may be required to replenish the depleted pools. It is likely
      that some, if not many, acinar cells may de-differentiate into intercalated duct
      like cells and thus add to the pool of progenitor cells in such situations. If
      the stress is heavy doses of radiation, however, the result is not only the death
      of acinar cells, but also a marked decline in functional differentiation and
      proliferative capacity of all of the surviving cells, including those with
      progenitor capability. Restoration of gland function, therefore, seems to require
      increasing the secretory capacity of the surviving cells, or replacing the acinar
      cells and their progenitors either in the existing gland remnants or with
      artificial glands.

PMID- 18828046
TI  - Acute erythema and edematous skin reaction and ectropion following docetaxel in a
      patient with non-small cell lung cancer.
AB  - Docetaxel can cause skin reactions such as hypersensitivity, edema, and
      erythrodysesthesia syndrome as well as side effects involving the skin, including
      alopecia, nail onycholysis, nail pigmentation, photosensitivity, scleroderma, and
      paresthesia. In this case report, a patient was admitted to the hospital with
      widespread erythematous and edematous eruption in the head, neck, trunk, and
      lower and upper extremities, erythema around the eyes, and drooping of the lower
      eyelids that developed about 2 hours after receiving chemotherapy consisting of
      docetaxel. Use of the Naranjo Adverse Drug Reaction Probability Scale--a method
      for estimating the probability of adverse drug reactions--indicated a probable
      relationship between the skin reaction and docetaxel therapy in this patient.
      Docetaxel-associated skin reactions that are so extensive and severe as to lead
      to eye madarosis and ectropion are reported rarely in the literature.

PMID- 18828047
TI  - Toward automatic adjustment of pointing device configuration to accommodate
      physical impairment.
AB  - PURPOSE: Software was developed which makes recommendations regarding
      configuration of a computer pointing device, such as a mouse, to accommodate a
      person's physical impairment. Specifically, a software agent automatically
      recommends a setting for the computer's control-display gain based on
      observations of a user's performance in a target selection task. METHOD: The
      software agent makes its recommendations based on available adjustment settings
      in the existing operating system. The agent was evaluated in studies with 12
      participants who have motor impairments. RESULTS: The agent-selected gain was not
      associated with significant improvements in selection time or error-free
      performance compared with the operating system's default gain. Across
      participants and trials, gain did not have a significant effect on selection time
      except at the lowest gain settings tested. However, two participants did have
      notable and consistent improvement in selection time and error-free performance
      using the agent-selected gain; gain across trials had a significant effect on
      number of target entries and number of submovements; and a post-hoc analysis
      indicated improved target selection time when varying both target size and
      control-display gain. CONCLUSION: These observations provide possible avenues for
      future work, although the current study indicates that changes to control-display
      gain, alone, are unlikely to offer improvements in speed or accuracy for the
      general population of people with motor impairments.

PMID- 18828048
TI  - Differentiating non-asbestiform amphibole and amphibole asbestos by size
      characteristics.
AB  - Mining or processing asbestos minerals can liberate isolated fibers or fiber
      bundles regulated as airborne asbestos fibers. Coarsely crystalline amphibole
      minerals are more common than asbestos in many geologic environments, and
      disturbance can result in the release of prismatic or acicular single crystals or
      cleavage fragments resembling asbestos fibers or fiber bundles but that are not
      currently regulated as asbestos. Bulk samples of six coarsely crystalline
      amphiboles and their five asbestos analogs were processed to maximize the number
      of particles meeting the criterion for counting under the current U.S. National
      Institute for Occupational Safety and Health Method 7400 "A" counting rules (> 5
      microm long with an aspect ratio >or= 3:1) and also within the respirable width
      range, i.e. < 3 microm width. The length distributions of the particles produced
      showed substantial overlap between cleavage fragments and asbestos fibers.
      Available data sets generally confirmed the relevance of the size distributions
      of particles generated from reference materials to airborne particles. The length
      criterion in the current ASTM International standard D7200-06 causes a large
      proportion (e.g., 40% grunerite and 39% tremolite) of the non-asbestiform
      particles to be considered potential asbestos. An alternative procedure may be to
      use a distinction based on width alone as some, but not the majority of, cleavage
      fragments were thinner than 1 microm (e.g., 9% of actinolite and 20% of grunerite
      particles), and not many amphibole asbestos particles were wider (e.g., 5% of
      crocidolite and 18% of amosite particles). This proposal would need further
      testing. This research should not be considered as addressing any controversy
      with regard to the toxicity of non-asbestiform amphibole particles of similar
      dimensions to asbestos particles.

PMID- 18828049
TI  - Periviable babies: Italian suggestions for the ethical debate.
AB  - With the advancement of medical technology, the outcomes for high-risk infants
      have greatly improved. However, hand and hand with the more positive result of
      saving neonates, modern neonatal intensive care has also brought to light several
      issues regarding the ethical grounds in infant care. One of the greatest problems
      concerns newborns at the threshold of viability. Treatment guidelines have been
      formulated for these babies in different countries all around the world and there
      is the general consensus to withhold resuscitation in neonates when gestational
      age in less than, or equal to 23 weeks, with intensive care ensured for infants
      at 25 weeks' gestational age. In order to provide helpful suggestions during the
      initial management of the threatened birth of an infant with a gestational age of
      25 completed weeks or less, we conducted a study for reviewing international
      studies on survival and morbidity rates, international guidelines and practice
      recommendations. This gave rise to the creation of a consensus document
      subsequently submitted to the Italian Scientific Societies for approval. The
      'Carta di Firenze' does not attempt to deal with the problems related to
      pediatric euthanasia or eugenetics: its aim is to protect the infant and the
      mother from undue suffering although addressing recommendations for the work of
      clinicians.

PMID- 18828050
TI  - Infantile hypertrophic pyloric stenosis: a comparative study of incidence and
      other epidemiological characteristics in seven European regions.
AB  - OBJECTIVE: The objective of this study was to present epidemiologic data on
      infantile hypertrophic pyloric stenosis (IHPS) from seven well-defined European
      regions, and to compare incidence and changes in incidence over time between
      these regions. METHODS: This was a population-based study using data from
      registries of congenital malformations (EUROCAT) for a period of more than two
      decades (1980-2002). RESULTS: A total of 2534 infants were diagnosed with IHPS
      during the study period, giving an overall incidence of IHPS of 2.0 per 1000 live
      births (LB), ranging from 0.86 per 1000 LB to 3.96 per 1000 LB in the seven
      regions. A significant decrease in incidence was observed in two regions and a
      significant increase in incidence was observed in two other regions. Young
      maternal age (<20 years) significantly increased the risk of IHPS by 29%
      (adjusted by region; p < 0.01), and at maternal age of 30 years and older the
      risk decreased significantly (p < 0.01). CONCLUSIONS: There were significant
      differences in the incidence of IHPS in the seven European populations. No
      uniform pattern of change in incidence was observed as the populations also
      differed in relation to trend over time with both significant increases and
      decreases over time. There is evidence that young maternal age is a risk factor
      for IHPS.

PMID- 18828052
TI  - Doppler analysis and placental nitric oxide synthase expression during fetal
      growth restriction.
AB  - OBJECTIVE: To assess placental nitric oxide (NO) metabolism related to changes in
      the uteroplacental circulation during fetal growth restriction (FGR). METHODS:
      The resistance index (RI) from the uterine arteries and pulsatility index (PI)
      from the umbilical artery were determined by Doppler analysis in 15 patients with
      FGR and 12 healthy controls, before elective cesarean section. Inducible (iNOS)
      and endothelial (eNOS) NO synthase expression were measured in placental samples.
      Immunohistochemistry was performed for iNOS location in the placenta. RESULTS:
      During FGR, we observed a significant elevation of iNOS when compared with
      controls. Conversely, eNOS did not differ between the two groups. A negative
      correlation with eNOS (r = -0.85) and a positive correlation with iNOS (r = 0.91)
      was found correlating to umbilical PI. The iNOS proteins were reduced in
      syncytiotrophoblast cells and increased in endothelium in the FGR group compared
      to the controls. CONCLUSIONS: During FGR, placental iNOS expression is
      significantly increased; this increase possibly represents an adaptive
      physiological mechanism for overcoming a fetoplacental circulation deficiency.

PMID- 18828053
TI  - Effect of fetal dexamethasone exposure on the development of adult insulin
      sensitivity in a rat model.
AB  - OBJECTIVE: A rat model was designed to determine if fetal dexamethasone exposure
      is associated with decreased insulin sensitivity in adulthood, manifested as
      decreased binding of p85 to phosphorylated insulin receptor substrate-1 (IRS-1)
      within the phosphatidylinositol 3-kinase (PI 3-kinase) pathway of insulin
      signaling. Additionally, the study investigated whether a differential effect
      exists in male and female rodent offspring, such that females demonstrate
      decreased binding of p85 to IRS-1 after exposure to dexamethasone in utero.
      METHODS: Timed-pregnant Sprague-Dawley rats received either tap water or
      dexamethasone in drinking water from day 13 of gestation until delivery. Fasting
      male and female offspring from each group were sacrificed on day 50 of life, and
      half of these rats were given insulin subcutaneously prior to sacrifice.
      Adipocyte, skeletal muscle, and liver cell lysates were analyzed by
      immunoprecipitation and Western blotting of IRS-1 and IRS-1-associated p85.
      RESULTS: In all tissues examined, a significant inverse relationship was found
      between dexamethasone treatment in utero and association of p85 with IRS-1 in
      adulthood. p85 association with IRS-1 was similar in tissues from fasting and
      insulin-stimulated states. Furthermore, tissues of male and female rats
      demonstrated similar binding of p85 to IRS-1. CONCLUSIONS: In a rat model, fetal
      exposure to dexamethasone was associated with decreased insulin signaling at the
      level of p85 binding to IRS-1, a proximal step in insulin signaling within the PI
      3-kinase pathway. This effect did not appear to be enhanced by administration of
      insulin prior to sacrifice, nor was a sex-dependent differential effect noted.

PMID- 18828051
TI  - Evidence of the involvement of caspase-1 under physiologic and pathologic
      cellular stress during human pregnancy: a link between the inflammasome and
      parturition.
AB  - OBJECTIVE: Caspase-1 is a component of the NALP3 inflammasome, a cytosolic
      multiprotein complex that mediates the processing of pro-inflammatory caspases
      and cytokines. The inflammasome represents the first line of defense against
      cellular stress and is a crucial component of innate immunity. Caspase-1 is the
      enzyme responsible for the cleavage and activation of interleukin (IL)-1 beta,
      which is a potent pro-inflammatory cytokine, and plays a central role in the
      mechanisms leading to labor (preterm and term) particularly in the context of
      intrauterine infection/inflammation. In addition, caspase-1 cleaves IL-18 and IL
      33. The objectives of this study were to determine whether there is a
      relationship between amniotic fluid concentrations of caspase-1 and gestational
      age, parturition (term and preterm), and intra-amniotic infection/inflammation
      (IAI). STUDY DESIGN: A cross-sectional study was conducted including 143 pregnant
      women in the following groups: (1) mid-trimester of pregnancy (n = 18); (2) term
      not in labor (n = 25); (3) term in labor (n = 28); (4) preterm labor (PTL) who
      delivered at term (n = 23); (5) PTL without IAI who delivered preterm (n = 32);
      (6) PTL with IAI who delivered preterm neonates (n = 17). Caspase-1
      concentrations in amniotic fluid were determined by a specific and sensitive
      immunoassay. Non-parametric statistics were used for analysis. RESULTS: (1)
      Caspase-1 was detected in amniotic fluid of women at term, but in none of the mid
      trimester samples. (2) Patients in labor at term had a significantly higher
      median amniotic fluid concentration of caspase-1 than women at term not in labor
      (term in labor: 10.5 pg/mL, range 0.0-666.0 vs. term not in labor: 5.99 pg/mL,
      range 0.0-237.4; p < 0.05). (3) Among patients with spontaneous PTL, those with
      IAI (median 41.4 pg/mL, range 0.0-515.0) had a significantly higher median
      amniotic fluid caspase-1 concentration than those without IAI who delivered
      preterm (median 0.0 pg/mL, range 0.0-78.4) and than those who delivered at term
      (median 0.0 pg/mL, range 0.0-199.5); p < 0.001 for both comparisons. CONCLUSIONS:
      (1) The presence and concentration of caspase-1 in the amniotic fluid varies as a
      function of gestational age. (2) Women with spontaneous labor at term had a
      higher median caspase-1 amniotic fluid concentration than women at term without
      labor. This suggests that the inflammasome may be activated in spontaneous
      parturition at term. Since most women with labor do not have intra-amniotic
      infection, we propose that cellular stress during labor accounts for activation
      of the inflammasome. (3) Preterm labor associated with infection/inflammation was
      also associated with a high concentration of caspase-1, suggesting that infection
      may induce caspase-1 production and activation of the inflammasome. (4) The
      sequential activation of the inflammasome and caspase-1, leading to interleukin-1
      beta processing and secretion, is a candidate pathway leading to the activation
      of the common pathway of parturition.

PMID- 18828055
TI  - Comparison of ceftriaxone versus triple drug regimen in the prevention of
      cesarean section infectious morbidities.
AB  - OBJECTIVE: To compare the effectiveness of single dose ceftriaxone versus
      multiple doses of ampiclox, gentamicin, and metronidazole to prevent infectious
      morbidity at elective cesarean section. METHODS: This was a randomized clinical
      trial involving 200 pregnant women who had an elective cesarean section for
      various reasons during the study period. Outcome measures included endometritis,
      urinary tract infections, febrile morbidities, wound infections, duration of
      hospital stay, and cost of antibiotic therapy. Data were managed using SPSS.
      RESULTS: There was no statistically significant difference in the mean duration
      of hospital stay between the two groups, but a significant statistical difference
      was found in the mean cost of antibiotic treatment ($15 for the combination and
      $9 for ceftriaxone; p = 0.000), with the group of patients taking a single dose
      of ceftriaxone (ROPHEX) having a lower mean cost of treatment than those taking a
      combination of ampiclox, gentamicin, and metronidazole. The study groups did not
      differ significantly in the incidence of endometritis (14% versus 15%), urinary
      tract infection (11% versus 15%), wound infections (7% versus 8%), febrile
      morbidity (7% versus 6%), and peritonitis (0% versus 0%). CONCLUSION: Single dose
      ceftriaxone was as effective as a combination of ampiclox, gentamicin, and
      metronidazole in preventing post-elective cesarean section complications.

PMID- 18828054
TI  - Pyelonephritis during pregnancy: a cause for an acquired deficiency of protein Z.
AB  - OBJECTIVE: Pyelonephritis has a more severe course during pregnancy than in the
      non-pregnant state. This has been attributed to the increased susceptibility of
      pregnant women to microbial products. An acquired protein Z deficiency has been
      reported when there is excessive thrombin activity. The aim of this study was to
      determine whether pyelonephritis during pregnancy is associated with changes in
      maternal plasma protein Z concentrations. STUDY DESIGN: A cross-sectional study
      was conducted to compare plasma protein Z concentrations between normal pregnant
      women (N = 71) and pregnant women with pyelonephritis (N = 42). Protein Z
      concentrations were measured by enzyme-linked immunosorbent assay. Parametric and
      non-parametric statistics were used for analysis. RESULTS: Patients with
      pyelonephritis had a significantly lower median plasma concentration of protein Z
      than did patients with normal pregnancies (median 2.14 microg/mL (0.4-3.4) vs.
      median 2.36 microg/mL (1.09-3.36); p = 0.03). There was no difference in the
      median plasma concentration of anti-protein Z antibodies between patients with
      pyelonephritis and those with normal pregnancies. CONCLUSION: The median maternal
      plasma protein Z concentration was significantly lower in patients with
      pyelonephritis during pregnancy than in patients with normal pregnancies.

PMID- 18828056
TI  - Exposure to active and passive smoking during pregnancy and severe small for
      gestational age at term.
AB  - OBJECTIVE: The objective of this study was to assess the relationship between
      active smoking as well as environmental tobacco smoke (ETS) exposure and severe
      small for gestational age (SGA) at term in a sample of pregnant Italian women.
      METHODS: A case-control study was conducted in nine cities in Italy between
      October 1999 and September 2000. Cases of severe SGA were singleton, live born,
      at term children with a birth weight <or= 5(th) percentile for gestational age.
      Controls (10:1 to cases) were enrolled from among singleton at term births that
      occurred in the same hospitals one or two days after delivery of the case, with a
      birth weight > 10(th) percentile for gestational age. A total of 84 cases of
      severe SGA and 858 controls were analyzed. A self-administered questionnaire was
      used to assess active smoking and ETS exposure, as well as potential confounders.
      RESULTS: Multivariate logistic regression analysis showed a relationship between
      active smoking during pregnancy and severe SGA (adjusted odds ratio (OR) 2.10,
      95% confidence interval (CI) 1.13-3.68). ETS exposure was associated with severe
      SGA (adjusted OR 2.51, 95% CI 1.59-3.95) with a dose-response relationship to the
      number of smokers in the home.

PMID- 18828057
TI  - The female condom as a temporary silo: a simple and inexpensive tool in the
      initial management of the newborn with gastroschisis.
AB  - OBJECTIVE: The aim of this study is to report the use of a female condom as a non
      surgical silon pouch in the early management of newborns with gastroschisis with
      large visceroabdominal disproportion. METHODS: Pre-washed, sterile female condoms
      without spermicide were used as an early approach to treat gastroschisis in 20
      newborns with large defects and in whom staged correction was anticipated. The
      condom was placed in the neonatal intensive care unit using sterile technique,
      with no anesthesia, and it was removed only at the time of the surgical procedure
      for gastroschisis correction. RESULTS: There were no complications associated
      with the use of a female condom as a temporary silo for gastroschisis. It
      protected the exposed organs and also allowed a careful evaluation of the bowel
      and a better pre-operative planning without the need for emergency procedures.
      CONCLUSION: The use of a female condom as a silon pouch is a low-cost and simple
      alternative in the initial management of newborns with gastroschisis in whom
      primary correction is considered non-feasible.

PMID- 18828058
TI  - The concentration of surfactant protein-A in amniotic fluid decreases in
      spontaneous human parturition at term.
AB  - OBJECTIVE: The fetus is thought to play a central role in the onset of labor.
      Pulmonary surfactant protein (SP)-A, secreted by the maturing fetal lung, has
      been implicated in the mechanisms initiating parturition in mice. The present
      study was conducted to determine whether amniotic fluid concentrations of SP-A
      and SP-B change during human parturition. STUDY DESIGN: Amniotic fluid SP-A and
      SP-B concentrations were measured with a sensitive and specific ELISA in the
      following groups of pregnant women: (1) mid-trimester of pregnancy, between 15
      and 18 weeks of gestation (n = 29), (2) term pregnancy not in labor (n = 28), and
      (3) term pregnancy in spontaneous labor (n = 26). Non-parametric statistics were
      used for analysis. RESULTS: SP-A was detected in all amniotic fluid samples. SP-B
      was detected in 24.1% (7/29) of mid-trimester samples and in all samples at term.
      The median amniotic fluid concentrations of SP-A and SP-B were significantly
      higher in women at term than in women in the mid-trimester (SP-A term no labor:
      median 5.6 microg/mL, range 2.2-15.2 microg/mL vs. mid-trimester: median 1.64
      microg/mL, range 0.1-4.7 microg/mL, and SP-B term no labor: median 0.54
      microg/mL, range 0.17-1.99 microg/mL vs. mid-trimester: median 0 microg/mL, range
      0-0.35 microg/mL; both p < 0.001). The median amniotic fluid SP-A concentration
      in women at term in labor was significantly lower than that in women at term not
      in labor (term in labor: median 2.7 microg/mL, range 1.2-10.1 microg/mL vs. term
      no labor: median 5.6 microg/mL, range 2.2-15.2 microg/mL; p < 0.001). There was
      no significant difference in the median amniotic fluid SP-B concentrations
      between women in labor and those not in labor (term in labor: median 0.47
      microg/mL, range 0.04-1.32 microg/mL vs. term no labor: median 0.54 microg/mL,
      range 0.17-1.99 microg/mL; p = 0.2). CONCLUSION: The amniotic fluid concentration
      of SP-A decreases in spontaneous human parturition at term.

PMID- 18828059
TI  - Prognostic parameters for successful external cephalic version.
AB  - OBJECTIVE: To improve patient consultation before external cephalic version (ECV)
      attempt at term by defining prognostic parameters for the success of the
      procedure. METHODS: This was a prospective observational study set in a
      university teaching hospital. We prospectively collected demographic and
      obstetric data from 603 ECV attempts at our center for the period between January
      1997 and June 2005. Analysis was performed by stepwise logistic regression of the
      demographic and obstetric parameters. The main outcome measure was success of ECV
      attempt. RESULTS: Success rates were 72.3% and 46.1% for multiparas and
      nulliparas, respectively. Prognostic parameters associated with successful ECV
      were amniotic fluid index > 7 cm, multiparity, non-frank breech, non-anterior
      placental location, and body mass index < 25. CONCLUSION: Prognostic parameters,
      particularly amniotic fluid index and multiparity, can help physicians in
      counseling parturients before deciding on ECV.

PMID- 18828060
TI  - Amniotic fluid concentration of surfactant proteins in intra-amniotic infection.
AB  - OBJECTIVE: Pulmonary surfactant is a complex molecule of lipids and proteins
      synthesized and secreted by type II alveolar cells into the alveolar epithelial
      lining. Both lipid and protein components are essential for lung function in
      postnatal life. Infection is a well-established cause of preterm delivery, and
      several inflammatory cytokines play a role in the mechanisms of preterm
      parturition. An increased concentration of inflammatory cytokines in amniotic
      fluid or fetal plasma has been linked to the onset of preterm parturition and
      fetal/neonatal injury, including cerebral palsy and chronic lung disease.
      Experimental evidence indicates that inflammatory mediators also regulate
      surfactant protein synthesis, and histologic chorioamnionitis is associated with
      a decreased incidence of hyaline membrane disease in neonates. This study was
      conducted to determine if amniotic fluid concentrations of surfactant protein
      (SP)-A, SP-B, and SP-D change in patients with and without intra-amniotic
      infection (IAI). MATERIALS AND METHODS: A case-control study was conducted to
      determine amniotic fluid concentrations of SP-A, SP-B, SP-D, and total protein in
      patients who had an amniocentesis performed between 18 and 34 weeks of gestation
      for the detection of IAI in patients with spontaneous preterm labor with intact
      membranes (n = 42) and cervical insufficiency prior to the application of
      cerclage (n = 6). Amniotic fluid samples were selected from a bank of biological
      specimens and included patients with (n = 16) and without (n = 32) IAI matched
      for gestational age at amniocentesis. Intra-amniotic infection was defined as a
      positive amniotic fluid culture for microorganisms. Each group was further
      subdivided according to a history of corticosteroid administration within 7 days
      prior to amniocentesis into the following subgroups: (1) patients without IAI who
      had received antenatal corticosteroids (n = 21), (2) patients with IAI who had
      received antenatal corticosteroids (n = 9), (3) patients without IAI who had not
      received antenatal corticosteroids (n = 11), and (4) patients with IAI who had
      not received antenatal corticosteroids (n = 7). Amniotic fluid was obtained by
      transabdominal amniocentesis. SP-A, SP-B, and SP-D concentrations in amniotic
      fluid were determined by enzyme-linked immunosorbent assay (ELISA). Non
      parametric statistics were used for analysis. RESULTS: Women with IAI had a
      higher median amniotic fluid concentration of SP-B and of SP-B/total protein, but
      not other SPs, than those without IAI (both p = 0.03). Among patients who had
      received antenatal corticosteroids, the median amniotic fluid concentration of SP
      B and of SP-B/total protein was significantly higher in patients with IAI than in
      those without IAI (SP-B, IAI: median 148 ng/mL, range 37.3-809 ng/mL vs. without
      IAI: median 7.2 ng/mL, range 0-1035 ng/mL; p = 0.005 and SP-B/total protein, IAI:
      median 14.1 ng/mg, range 4.3-237.5 ng/mg vs. without IAI: median 1.45 ng/mg,
      range 0-79.5 ng/mg; p = 0.003). Among women who had not received antenatal
      corticosteroids, the median amniotic fluid concentrations of SP-B and of SP
      B/total protein were not significantly different between patients with and
      without IAI (SP-B, IAI: median 4 ng/mL, range 0-31.4 ng/mL vs. without IAI:
      median 3.4 ng/mL, range 0-37 ng/mL; p = 0.8 and SP-B/total protein, IAI: median
      0.55 ng/mg, range 0-6.96 ng/mg vs. without IAI: median 0.59 ng/mg, range 0-3.28
      ng/mg; p = 0.9). The median amniotic fluid concentrations of SP-A, SP-A/total
      protein, SP-D, and SP-D/total protein were not significantly different between
      patients with and without IAI whether they received antenatal corticosteroids or
      not (all p > 0.05). CONCLUSIONS: IAI was associated with an increased amniotic
      fluid concentration of SP-B in patients who received antenatal corticosteroids
      within 7 days prior to amniocentesis.

PMID- 18828061
TI  - Sildenafil administration to a patient with refractory persistent pulmonary
      hypertension of the newborn.

PMID- 18828062
TI  - American Chemical Society--236th National Meeting & Exposition. Compound
      development for prevalent conditions.

PMID- 18828063
TI  - American Chemical Society--236th National Meeting & Exposition. Highlights of
      compound research.

PMID- 18828064
TI  - American Chemical Society--236th National Meeting & Exposition. Drug development
      for tuberculosis and cancer.

PMID- 18828065
TI  - American Chemical Society--236th National Meeting & Exposition. New frontiers in
      drug delivery.

PMID- 18828066
TI  - Drug Discovery and Development of Innovative Therapeutics--IBC's 13th Annual
      World Congress. Approaches to cancer therapy.

PMID- 18828067
TI  - Frontiers in immunology research network--2008 International Conference.

PMID- 18828068
TI  - Clinical Pharmacology of Antimalarial Drugs--First AHRO International Malaria
      Symposium.

PMID- 18828069
TI  - World Summit of Antivirals--BIT Life Sciences' First Annual Summit. Combating
      severe viral infections.

PMID- 18828070
TI  - British Association for Psychopharmacology--2008 Summer Meeting.

PMID- 18828071
TI  - Clinical Research in Emerging Countries--Third Annual Marcus Evans Conference.

PMID- 18828072
TI  - Toward in silico approaches for investigating the activity of nanoparticles in
      therapeutic development.
AB  - The distinctive characteristics of nanoparticles (NPs), resulting from properties
      that arise at the nanoscale, are stimulating the use of these particles in the
      biomedical sector for diagnostic and therapeutic purposes. However, these same
      characteristics of NPs also underlie widespread concerns regarding potential
      toxic effects. Given the large number of NPs that are being developed for
      possible biomedical use, there is a need to develop rapid screening methods based
      on in silico methods. This feature review provides an overview of some of the
      main in silico methods that are already used in the assessment of chemicals. The
      current status of these methods, in terms of availability and applicability to
      NPs, and recommendations for further research, are highlighted.

PMID- 18828073
TI  - Living without a data management system.
AB  - The implementation of a typical electronic data capture (EDC) system for clinical
      trials - encompassing data entry, validation and reporting tools - involves
      modeling electronic case report forms (eCRFs) for data that will be entered by
      investigative trial sites, providing web access for the sites to enter the data,
      managing a 'cleaning and locking' process (in which any queries against the data
      are resolved), and transmitting the final data to SAS datasets. Other clinical
      data not included in CRFs, such as laboratory data, are typically handled in a
      separate clinical data management system; this information is not directly linked
      back to the trial sites and therefore is inaccessible for review. Thus,
      activities such as seeking site feedback on out-of-range laboratory values can
      only be performed by manually transcribing queries from the data management
      system into the EDC system. As the number of studies using EDC systems escalates
      and the number of studies gathering data on paper diminishes, the inefficiencies
      of handling data across different systems are becoming increasingly apparent.
      This article explores the opportunities, risks and technical requirements needed
      for an integrated EDC environment to enable a discontinuation of the use of older
      data management systems.

PMID- 18828074
TI  - R-1626, a specific oral NS5B polymerase inhibitor of hepatitis C virus.
AB  - Roche Holding AG is developing R-1626, an oral nucleoside inhibitor of HCV RNA
      polymerase. R-1626 has been demonstrated to be well absorbed and rapidly
      converted to the active component R-1479. The compound has demonstrated a strong
      capacity to inhibit HCV replication in vitro and in vivo, without the rapid
      development of viral resistance. After 4 weeks of treatment with R-1626 in
      combination with PEG-IFN plus ribavirin in treatment-naive patients with genotype
      1 HCV infection, HCV RNA could no longer be detected in approximately 74% of
      patients, compared with 5% of patients treated with PEG-IFN plus ribavirin alone,
      indicating the high potency of R-1626 to induce HCV RNA viral load reductions. R
      1626 was generally well tolerated, although severe side effects of neutropenia
      were observed at high doses. A phase IIb clinical trial was ongoing at the time
      of publication to test the efficacy of R-1626 in combination with a standard or
      lower dose of PEG-IFN and ribavirin in HCV genotype 1-infected patients. Given
      its potent antiviral effect with an apparent high genetic barrier, R-1626
      represents an important advancement in improving the outcome of patients with
      chronic HCV infection.

PMID- 18828075
TI  - Mucosal morphology in Barrett's esophagus: interobserver agreement and role of
      narrow band imaging.
AB  - BACKGROUND AND STUDY AIMS: We have recently proposed a classification of mucosal
      morphology in Barrett's esophagus based on three criteria: regularity of mucosal
      pattern, regularity of vascular pattern, and presence of abnormal blood vessels.
      We aimed to evaluate the interobserver agreement with the proposed mucosal
      morphology classification and to assess the additional value of narrow band
      imaging (NBI) over high resolution white light endoscopy (HR-WLE). PATIENTS AND
      METHODS: Five international experts in the field of Barrett's imaging and seven
      community endoscopists with no expertise in this field independently evaluated
      magnified still images from 50 areas, obtained with HR-WLE and NBI, in Barrett's
      esophagus patients. Visual analogue scales (VAS) were used for scoring imaging
      quality. Interobserver agreement for mucosal morphology and yield for identifying
      early neoplasia were assessed. RESULTS: Imaging qualities of NBI were rated more
      highly than HR-WLE, when evaluated separately as well as in a side-by-side
      comparison. The interobserver agreement ranged from 0.40 to 0.56 and did not
      significantly differ between expert and non-expert endoscopists. The overall
      yield for correctly identifying images of early neoplasia was 81 % for HR-WLE, 72
      % for NBI and 83 % for HR-WLE + NBI, with no significant difference between
      experts and non-experts. CONCLUSION: Interobserver agreement for the
      classification of mucosal morphology was moderate. Although NBI was rated more
      highly than HR-WLE for imaging quality, this did not result in improved
      interobserver agreement or increased yield for identifying early neoplasia in
      Barrett's esophagus. This applied to non-expert as well as expert endoscopists.

PMID- 18828076
TI  - Endoscopic resection of sporadic duodenal adenomas: an efficient technique with a
      substantial risk of delayed bleeding.
AB  - INTRODUCTION: Data on endoscopic resection of sporadic duodenal adenoma (SDA) are
      sparse; we present our results concerning safety and efficacy in a retrospective
      analysis of saline-assisted endoscopic resection of SDA. PATIENTS AND METHODS:
      The cases of all patients who underwent endoscopic resection for SDA between May
      1998 and May 2006 were analyzed. Endoscopic resection was carried out using
      standard injection and cut methods. In some patients hemoclips and argon plasma
      coagulation were used, either for prophylaxis or for the treatment of procedure
      related bleeding. RESULTS: Thirty-six patients with a total of 37 lesions (mean
      size 19 mm, range 4 - 50 mm) were analyzed. Lesions larger than 20 mm were more
      frequently resected piecemeal ( P = 0.022). Intraprocedural bleeding occurred in
      14 % of cases, without any significant association with lesion size or the
      resection technique. One fatal perforation occurred. Macroscopically complete
      resection was achieved in 97 % of cases, as confirmed by at least one negative
      control endoscopy with biopsies after a mean follow-up of 15 months. Although
      clipping and argon plasma coagulation were not applied in any systematic way, it
      was noticeable that in the 20 cases in which they were used for hemostasis or
      prevention, no delayed bleeding was observed after the procedures. In contrast,
      bleeding occurred in 22 % of the 23 procedures performed without these additional
      techniques. CONCLUSION: Endoscopic resection is an efficient and acceptably safe
      technique for treating SDA. Further studies need to assess whether systematic
      bleeding prophylaxis will reduce the incidence of delayed hemorrhage after
      endoscopic resection.

PMID- 18828077
TI  - Narrow band imaging with magnification for the characterization of small and
      diminutive colonic polyps: pit pattern and vascular pattern intensity.
AB  - BACKGROUND AND STUDY AIMS: Narrow band imaging (NBI) can accurately characterize
      colonic polyps using microvascular appearances. We aimed to assess whether the
      Kudo pit pattern classification is accurate when used with NBI (without dye
      spray), and if microvascular appearances or NBI pit patterns maintain accuracy
      for polyp characterization at sizes < 10 mm. PATIENTS AND METHODS: 116 polyps <
      10 mm in size were detected in 62 patients undergoing surveillance colonoscopy.
      The polyps were prospectively assessed using NBI and magnification for Kudo pit
      pattern (III-V neoplastic, I-II non-neoplastic) and vascular pattern intensity
      (VPI), a measure of microvascular density (strong VPI, neoplastic; normal or weak
      VPI, non-neoplastic). Sensitivity, specificity, and accuracy were calculated and
      compared with results from histopathology. RESULTS: The mean polyp size was 3.4
      mm (range 1 - 9 mm). Overall, NBI pit pattern sensitivity, specificity, and
      accuracy were 0.88, 0.91, and 89.6 %, respectively. Equivalent values for VPI
      were 0.94, 0.89, and 91.4 %. Results were similar when polyps were subdivided
      into diminutive polyps (size <or= 5 mm) and flat polyps. Combining both pit
      pattern and VPI improved the sensitivity (0.98, P = 0.06 versus NBI pit pattern
      alone). There was very good agreement between NBI pit pattern and VPI for
      prediction of dysplasia (kappa = 0.83). No evidence of a learning curve for VPI
      was found. The NBI pit pattern was better than the VPI at subclassifying
      hyperplastic from other non-neoplastic polyps (sensitivity 0.79 versus 0.56,
      respectively, P = 0.02), but accuracy was poor. CONCLUSION: The NBI pit pattern
      and VPI are both highly accurate in characterizing neoplastic colonic polyps of <
      10 mm, with VPI appearing to be simple to learn. NBI has the potential to replace
      conventional histology for small polyps.

PMID- 18828078
TI  - Reflux disease and Barrett's esophagus.

PMID- 18828079
TI  - Gastrointestinal bleeding.

PMID- 18828080
TI  - Small-bowel endoscopy.

PMID- 18828081
TI  - Colon tumors and colonoscopy.

PMID- 18828082
TI  - Endoscopic ultrasound.

PMID- 18828083
TI  - ERCP topics.

PMID- 18828084
TI  - Endoscopic diagnosis and treatment of upper gastrointestinal tumors.

PMID- 18828085
TI  - NOTES.

PMID- 18828086
TI  - Small papilla: another risk factor for post-sphincterotomy perforation.

PMID- 18828090
TI  - Cat scratch colon is caused by barotrauma secondary to insufflation during
      colonoscopy.

PMID- 18828092
TI  - Light blue crest sign, a favorable marker for predicting the severity of gastric
      atrophy in the entire stomach.

PMID- 18828095
TI  - A review of the distribution of the arterial and venous vasculature of the
      diaphragm and its clinical relevance.
AB  - The diaphragm is the major respiratory muscle of the body. As it plays such a
      vital role, a continuous arterial and venous blood supply is of the utmost
      importance. It is therefore not surprising to find described in the literature a
      complex system of anastomoses that contributes to the maintenance of this
      muscle's life-preserving contraction. Understanding the anatomy of the diaphragm
      and any divergence in its vasculature is literally vital to humanity. In the
      light of this, we review the literature on the blood supply to the diaphragm,
      with specific emphasis on the recent description of the inferior phrenic vessels
      and the superior phrenic artery, summarize the clinical significance of the
      diaphragmatic vasculature and suggest future avenues of study to further expand
      on this current body of knowledge.

PMID- 18828096
TI  - The ansa subclavia: a review of the literature.
AB  - The ansa subclavia, subclavian loop, Vieussens' ansa or Vieussens' loop is a
      nerve cord that connects the middle cervical and inferior cervical sympathetic
      ganglia, forming a loop around the subclavian artery. The structure of the ansa
      subclavia is evolutionarily conserved from rats, guinea pigs, the porcine species
      and dogs to humans. A common application in physiological studies is to
      electrically stimulate the ansa subclavia in animal models as a robust protocol
      to modulate stimulatory cardiac sympathetic input. Despite a large number of
      physiological studies utilizing the ansa subclavia, only very brief descriptions
      have been devoted to it in standard anatomy texts. An extensive search found only
      one report in the English language literature concerning the anatomy of the ansa
      subclavia. The aim of this report, therefore, was to provide a comprehensive
      review of the clinical anatomy of the ansa subclavia and to discuss its potential
      physiological functions.

PMID- 18828097
TI  - The body constitution of patients and intubation scales as predictors of
      difficult intubation considered in relation to the experience of the intubator.
AB  - The aims of the study were to identify factors that may result in difficulties in
      intubation, and to compare the results obtained when an experienced and when a
      less experienced anaesthesiologist was involved. The 96 patients included in the
      study were evaluated for difficult intubation according to the following scales:
      Mallampati, upper lip bite test (ULBT) and Patil. The mobility of the cervical
      segments of the vertebral column, the distance between the jugular notch of the
      sternum and the chin and the anatomical constitution of the body were other
      factors that were taken into consideration. Statistical analysis was performed in
      order to identify factors that may result in difficulties in intubation for an
      experienced and for a less experienced anaesthesiologist.

PMID- 18828098
TI  - The diagnostic value of the resistivity index of the common carotid arteries in
      severe internal carotid artery stenosis.
AB  - Duplex ultrasound is currently used both for screening and for preoperative
      assessment of the carotid arteries and has completely replaced carotid
      angiography for the latter purpose in many institutions. The study aimed to
      identify resistivity index abnormalities in the common carotid arteries in
      patients with occluded or severely stenosed internal carotid arteries. Sixteen
      patients with severe internal carotid artery stenosis or occlusion over a twelve
      month period were studied by duplex ultrasonography. The resistivity index in the
      common carotid artery was 0.85 +/- 0.03 on the stenotic side compared to 0.74 +/-
      0.04 on the opposite side (p < 0.05). There was no side difference regarding flow
      velocity. In patients with occluded or severely stenosed internal carotid
      arteries compensatory vasodilation occurs in cerebral vessels on the same side,
      and this is also significant, resulting in a decrease in the resistivity index in
      the common carotid artery of the opposite side.

PMID- 18828099
TI  - Comparison of the blood vessel complexes of the human and bovine male gonads.
AB  - The aim of the study was to compare the blood vessel network of the human and
      bovine male gonads, paying special attention to differences resulting from
      mediastinum testis localisation. Two groups of specimens were compared. Each
      group consisted of 50 corrosive die casts of the testicular and spermatic cord
      vessels of bovine and human gonads respectively. In each group 20 gonads had only
      the arterial vessels injected, another 20 only the veins, while in 10 gonads both
      arteries and veins were injected. The die casts were examined with a stereoscopic
      binocular as well as an optic microscope. The different testicular vascular
      patterns in humans and bulls were observed. In humans the intratesticular
      arteries branch off the arterial network of the tunica albuginea and mediastinum
      testis. The former runs centripetally, the latter centrifugally. Analogically,
      the intratesticular veins emptying into the tunica albuginea venous network run
      centrifugally and those emptying into the mediastinum testis plexus run
      centripetally. In bulls the arterial vessels run centripetally, later forming a
      helical, screw-like layer to give off centrifugal branches. Venous vessels run
      centrifugally and empty into the venous plexus of the tunica albuginea.

PMID- 18828100
TI  - Digital-image analysis of the left common carotid artery in human foetuses.
AB  - The rate of growth of the left common carotid artery during gestation has not
      been sufficiently evaluated. The present study was performed on 128 spontaneously
      aborted human foetuses aged 15-34 weeks to compile normative data for the
      dimensions of the left common carotid artery at varying gestational ages. Using
      anatomical dissection, digital image analysis (system of Leica Q Win Pro 16) and
      statistical analysis (ANOVA, regression analysis), a range of measurements
      (length, original external diameter and volume) for the left common carotid
      artery during gestation was examined. No significant gender differences were
      found (p > 0.05). The growth curves of the best fit for the plot of each
      morphometric parameter against gestational age were generated. The lengths ranged
      from 14.82 +/- 2.22 to 42.84 +/- 4.32 mm, according to the linear model y = 
      9.6918 + 1.5963 x +/- 3.1706 (r = 0.95; p < 0.001). The original external
      diameter increased from 0.72 +/- 0.18 to 3.28 +/- 0.40 mm, according to the
      linear function y = -1.5228 + 0.1428 x +/- 0.2749 (r = 0.95; p < 0.001). The left
      common carotid artery-to-aortic root diameter ratio increased from 0.356 +/-
      0.062 to 0.480 +/- 0.101. The left common carotid artery-to-aortic arch diameter
      ratio increased from 0.447 +/- 0.079 to 0.535 +/- +/- 0.113. The volume ranged
      from 6.73 +/- 4.06 to 369.30 +/- 107.42 mm3 in accordance with the quadratic
      function y = 344.8 - 41.001 x + 1.254 x2 +/- +/- 46.955 (R2 = 0.87). The
      parameters examined have clinical application in the early recognition of
      arterial abnormalities, especially aortic coarctation.

PMID- 18828101
TI  - Intraluminal septation of the basilar artery: incidence and potential clinical
      significance.
AB  - Variations in the cerebrovascular tree can increase surgical or interventional
      morbidity. To date, only scant comments are to be found in the literature
      regarding intraluminal variations of the basilar artery. To further elucidate
      such anatomy, a cadaveric study was performed. One hundred and fifty human brains
      were evaluated for the present study. The basilar artery was identified in each
      and sectioned longitudinally to observe for the presence of intraluminal septa.
      One specimen (0.67%) was identified that harbored an intraluminal septum of the
      basilar artery. This wall was within the proximal basilar artery and measured 3
      mm by 1.5 mm. No specimen was found to have other anomalies of the basilar artery
      and in the single specimen with an intraluminal septum no signs of intracranial
      pathology were seen. Although seemingly rare, septation of the basilar artery can
      be found. Knowledge of such an intraluminal vascular variation may be important
      during invasive and minimally invasive procedures.

PMID- 18828102
TI  - The granule cell density of the dentate gyrus following administration of Urtica
      dioica extract to young diabetic rats.
AB  - Urtica dioica L. Stinging nettle has long been known worldwide as a medicinal
      plant. To study the benefits of the nettle in diabetic encephalopathy, the
      granule cell density of the dentate gyrus of diabetic rats was studied following
      administration of Urtica dioica extract. A total of 24 male albino Wistar rats
      were allocated equally to normal, diabetic, preventive and treatment groups.
      Hyperglycaemia was induced by streptozotocin (80 mg/kg) in the animals of the
      diabetic and treatment groups. One week after injection of the streptozotocin the
      animals in the treatment group received a hydroalcoholic extract of Urtica dioica
      (100 mg/kg/day) for 4 weeks intraperitoneally. The rats of the preventive group
      received hydroalcoholic extract of U. dioica (100 mg/kg/day) IP for the first 5
      days and an injection of streptozotocin (80 mg/kg) on the 6th day. After 5 weeks
      of study all the rats were sacrificed and coronal sections were taken from the
      dorsal hippocampal formation of the right cerebral hemispheres and stained with
      cresyl violet. The area densities of the granule cells were measured and compared
      in the four groups. The density was lower in the diabetic rats compared with the
      controls (p > 0.05). The preventive group showed lower cell density than the
      controls (p > 0.05). The densities in the treated rats were higher than in the
      diabetic rats (p > 0.05). Furthermore, the control and treated rats showed
      similar densities (p > 0.05). It seems that U. dioica extract can help compensate
      for granule cell loss in the diabetic rat dentate gyrus, which can ameliorate
      cognitive impairment in diabetes. However, preventive use of the extract showed
      no significant benefit.

PMID- 18828103
TI  - The thickness of the ventral midline of the spinal cord in human embryos during
      the fifth week.
AB  - The thickness of the ventral midline of the spinal cord was determined in 9 human
      embryos aged five weeks (developmental stages 13-15). This part of the spinal
      cord consists of floor plate, mantle and marginal layers. The floor plate
      ependymal cells form pseudostratified columnar epithelium. The thickness of the
      investigated structure varied from 20 to 50 micrometers at different levels of
      the spinal cord.

PMID- 18828104
TI  - Arterial supply and venous drainage of the choroid plexus of the human lateral
      ventricle in the prenatal period as revealed by vascular corrosion casts and SEM.
AB  - The topography of the arterial supply and venous drainage was visualised by
      corrosion casting and scanning electron microscopy in the human foetal (20 weeks)
      choroid plexus of the lateral ventricle. Although secondary villi were not yet
      present at that developmental stage, the topography of the large arteries and
      veins almost fully corresponded to that described in adult individuals. The only
      major difference observed was a lack of the typical tortuosity of the lateral
      branch of the anterior choroidal artery and of the superior choroidal vein, which
      probably develops during further expansion of the vascular system associated with
      the formation of secondary villi.

PMID- 18828105
TI  - A case of May-Thurner syndrome.
AB  - May-Thurner syndrome is a condition that results from narrowing of the left
      common iliac vein lumen due to pressure from the right common iliac artery as it
      crosses anterior to it. We describe a very rare case in which a previously
      asymptomatic patient presented with May-Thurner syndrome.

PMID- 18828106
TI  - Evidence of lateral antebrachial cutaneous nerve entrapment during autopsy.
AB  - Compression of the lateral cutaneous nerve of the forearm is a rare clinical
      entrapment syndrome. This report describes the compression of the lateral
      antebrachial cutaneous nerve at the level of the lateral margin of the biceps
      brachii tendon identified during autopsy. This is the first cadaveric case
      reported in the literature. The anatomy, the possible areas of entrapment, the
      most frequent diagnostic problems and the main therapeutic options for this rare
      occurrence are also discussed.

PMID- 18828108
TI  - [The nephrologist in the spotlight].

PMID- 18828109
TI  - [Is more always better? Treatment of acute renal failure in the critical patient:
      in search of the lost target].

PMID- 18828110
TI  - [Fighting against ESRD: a first victory?].

PMID- 18828111
TI  - [Obesity and renal disease: a ''fat'' public health issue].

PMID- 18828112
TI  - [The heart may... betray at any age!].

PMID- 18828113
TI  - [Urotension II and renal disease: protective or causal role?].

PMID- 18828114
TI  - [The low-protein diet in chronic kidney disease: still a valid prescription?].
AB  - Low-protein diets were originally identified as a therapeutic tool to alleviate
      symptoms and signs of uremia. Their prescription, however, became common in the
      1980s to reduce the rate of progression of chronic kidney disease. Since then,
      several studies of this nonpharmacological intervention have been published. In
      particular, the Modification of Diet in Renal Disease (MDRD) study, which is a
      cornerstone of the nephrology literature, was specifically aimed at verifying the
      effectiveness of low-protein diets; the results, however, were negative.
      Therefore, the diet issue progressively disappeared from scientific meetings and
      journals, and as a consequence also its use in clinical practice has diminished.
      The aim of this paper is to describe the state of the art of low-protein diets
      almost 15 years from the publication of the MDRD study.

PMID- 18828115
TI  - [Diuretics for acute kidney injury. Is there a rationale for their
      administration?].
AB  - Acute kidney injury (AKI) is a frequent and severe disorder that is observed in a
      variety of clinical settings. Early recognition of this syndrome is of critical
      importance in order to prevent progression to more severe forms, which are
      associated with a higher risk of complications and death. Efforts to prevent AKI
      have been made through a variety of interventions and drugs. However, no benefit
      has been demonstrated to date except for volume expansion and avoidance of
      nephrotoxic drugs. Diuretics have been extensively studied because of their main
      pharmacokinetic actions: reduction of renal vascular resistance and inhibition of
      active transport in the thick ascending limb, which reduces the energy
      requirement and eventually protects cells under ischemic conditions. Loop
      diuretics such as furosemide have been extensively tested to prevent AKI as well
      as to treat established AKI. Although experimental trials demonstrated that the
      administration of furosemide prevents the onset of AKI, no clinical trial has
      been able to reproduce this beneficial effect in humans. Moreover, there is
      evidence of impairment of renal function associated with it use. Like loop
      diuretics, mannitol induces diuresis in patients at risk of AKI but does not
      reduce its incidence. Recently, studies have demonstrated that natriuretic
      peptides such as h-ANP and nesiritide were associated with a reduction of the
      incidence of AKI in cardiac surgery patients. These promising results need to be
      confirmed in larger studies.

PMID- 18828116
TI  - [The role of endothelial progenitor cells in renal disease].
AB  - Recent evidence suggests that injury to the renal vasculature may play an
      important role in the pathogenesis of both chronic and acute ischemic kidney
      injury. Early alterations in peritubular capillary blood flow during reperfusion
      have been documented and associated with loss of normal endothelial cell
      function. In addition, ischemia induces alterations in endothelial cells that may
      promote inflammation and procoagulant activity, thus contributing to vascular
      congestion. Reduction of the microvasculature density increases hypoxia-mediated
      fibrosis and alters proper hemodynamics, which may lead to hypertension. This may
      play a critical role in the progression of chronic kidney disease following
      initial recovery from ischemia/reperfusion-induced acute kidney injury. The
      turnover and replacement of endothelial cells is therefore an important mechanism
      in the maintenance of vascular integrity also in the kidney. It is becoming clear
      that impaired vascular repair mechanisms as a result of a reduced number and/or
      impaired function of endothelial progenitor cells may contribute to renal
      disease. Moreover, investigators have begun to identify potential mechanisms
      responsible for the loss of function of endothelial progenitors in renal disease.
      In allografts, persistent injury results in excessive turnover of graft vascular
      endothelial cells. Moreover, chronic damage elicits a response that is associated
      with the recruitment of both leukocytes and endothelial progenitors, facilitating
      an overlapping process of inflammation and angiogenesis. In conclusion,
      angiogenesis and endothelial cell turnover play a pivotal role in renal disease
      and allograft rejection. Manipulation of these processes might have important
      implications for the development of novel therapeutic strategies in the near
      future.

PMID- 18828117
TI  - [Latin-American Dialysis and Kidney Transplantation Registry: data on the
      treatment of end-stage renal disease in Latin America].
AB  - Latin America, a region composed of a series of neighboring countries that share
      their history, Latin ancestry and language (Spanish or Portuguese), includes
      Mexico, Central America, the Spanish Caribbean islands, and South America. The
      Latin-American Dialysis and Kidney Transplantation Registry, which has been
      operative since 1991, collects data from 20 countries (Argentina, Brazil,
      Bolivia, Chile, Colombia, Costa Rica, Cuba, Ecuador, El Salvador, Guatemala,
      Honduras, Mexico, Nicaragua, Panama, Paraguay, Peru, Puerto Rico, Dominican
      Republic, Venezuela and Uruguay), where 97% of Latin Americans live. The
      prevalence of renal replacement therapy (RRT) has increased from 119 patients per
      million (pmp) in 1991 to 478.2 in 2005 (147,158 patients [57%] on chronic
      hemodialysis, 58,251 [23%] on peritoneal dialysis and 52,565 [20%] living with a
      functioning kidney graft). The incidence rate also increased from 27.8 pmp in
      1992 to 167 in 2005. The increment in prevalence and incidence occurred in all
      Latin- American countries. The transplantation rate increased from 3,7 pmp in
      1987 to 15 pmp in 2005 (7,968 kidney transplants performed this year, the
      cumulative number being 98,415). Access to RRT was available for every patient
      diagnosed with end-stage renal disease only in Argentina, Brazil, Chile, Cuba,
      Puerto Rico, Venezuela and Uruguay. In Latin America, the incidence and
      prevalence of RRT increased year by year. Only in some countries is access to RRT
      available to 100% of diagnosed patients. Detection and prevention programs for
      chronic kidney disease are needed in the region. Meanwhile, access to RRT has to
      be improved for everybody who needs it.

PMID- 18828118
TI  - [Clearances in automated intermittent peritoneal techniques: a new formula to use
      morning blood sampling].
AB  - According to the main guidelines, dialysis adequacy monitoring is fundamental in
      the management of patients on peritoneal dialysis. In order to avoid mistakes in
      the calculation of the peritoneal urea and creatinine clearance in patients on
      dialysis with intermittent techniques, the collection of blood samples about 6
      hours after the end of the dialysis session is advised. In fact, because the
      creatinine and urea values at the end of dialysis (the morning values in NIPD)
      are the lowest, the resulting clearances could be overestimated. The mean values
      between the start and the end of the dialysis session are considered the gold
      standard. However, collecting a blood sample at 2.00 p.m. may be difficult and
      uncomfortable both for the nurse and the patient. In this paper we present two
      formulas (the first for urea and the second for creatinine) which, starting from
      the values at the end of dialysis, predict the values at the beginning of the
      session and consequently the mean values. The aim of this study was to validate
      the formulas by evaluating their capability to predict the mean urea and
      creatinine values when only end-of-dialysis blood sampling was performed.
      Statistical analysis was carried out using the Bland-Altman test. The two
      formulas proved able to predict the mean urea and creatinine values; the
      differences between the measured and calculated values were not statistically
      significant.

PMID- 18828119
TI  - [Pneumaturia in a hemodialyzed diabetic. Case report].
AB  - The emphysematous cystitis is a rare condition, usually with a favorable
      prognosis; it is characterized by the presence of air in the bladder lumen and/or
      wall caused by the fermentation of glucose due to the action of microorganisms.
      Here the case is described of a hemodialyzed diabetic oligoanuric patient
      suffering from frequent symptomatic relapses of urinary tract infection, with air
      in the bladder and reported pneumaturia. The diagnostic workup aimed to exclude
      the presence of enterovesical fistulas, which are a possible cause of the
      presence of air in the urinary tract. The air was produced by bacteria isolated
      in the urine culture. Both the dysuric symptoms and the gas disappeared after
      appropriate antibiotic treatment.

PMID- 18828120
TI  - [The Classics of Italian Nephrology: ''The physiopathological basis for the
      nosography and the classification of bilateral kidney diseases'' by Pio Bastai
      (1888-1975) and Massimo Crepet (1911-1994)].
AB  - The paper ''I fondamenti fisiopatologici per la nosografia e la classificazione
      delle malattie renali bilaterali'' (The physiopathological basis for the
      nosography and the classification of bilateral kidney diseases'') by Pio Bastai
      (1888-1975) and Massimo Crepet (1911-1994) was presented at the 54th Congress of
      the Italian Society of Internal Medicine, which was held in October 1953 in Rome.
      In the report, the authors proposed their own classification of renal diseases
      based on a ''physopathological'' criterion and different from the classifications
      proposed by other authors of the period. According to Bastai and Crepet, renal
      diseases could be classified into arteriolopathies (either acute or chronic),
      capillary diseases (glomerulonephritides, including inflammatory and
      noninflammatory forms), renal diseases due to circulatory failure, nephropathies
      due to toxic substances, interstitial nephropathies, and idiopathic
      nephropathies. Of particular interest today is the part of the paper on the
      nosography of the so-called ''genuine glomerulonephrosis'' which, at variance
      with the view of the leading clinicians at the time, was placed among the
      inflammatory glomerulonephritides. In addition, the authors expressed their
      uncertainty about the existence of primary chronic interstitial nephropathies.
      Today, the paper by Bastai and Crepet shows how difficult it was to propose a
      classification of renal diseases in a period when the use of renal biopsy was
      still in its infancy.

PMID- 18828121
TI  - [Quality of life after kidney transplant].

PMID- 18828122
TI  - [Should dialysis be for all? A comment by Quirino Maggiore].

PMID- 18828124
TI  - [Calcineurin inhibitors: dose minimization].

PMID- 18828125
TI  - [Low-protein dietary therapy in patients with chronic kidney disease].
AB  - Several prospective studies and meta-analyses including the recent Cochrane meta
      analysis have demonstrated that reducing the protein content in the diet delays
      renal death and the start of dialysis in patients with chronic kidney disease
      (CKD). Reducing the dietary protein intake offers other benefits such as lowering
      accumulation of uremic toxins and circulating phosphates and improving symptoms
      and metabolic derangements. Following the publication of the Cochrane meta
      analysis, some of the most renowned experts in Italy on dietary therapy in the
      CKD patient established a working group within the Italian Society of Nephrology
      (SIN), the ''Nephrontieres'' project. The current supplement of GIN presents the
      views of the members of the ''Nephrontieres'' group on a range of issues related
      to dietary therapy in CKD. A CME program for Italian nephrologists also
      originated from the collaborative work of the group.

PMID- 18828126
TI  - [Prevalence of chronic kidney disease].
AB  - The prevalence of chronic kidney disease (CKD), especially the early stages, is
      still not exactly known. This is also true for CKD stage 3, when cardiovascular
      and other major complications generally appear. The NANHES data have shown a
      steady increase in the prevalence of CKD 3 up to 7.7% in 2004. Chronic kidney
      disease and renal failure are underdiagnosed all over the world. In Italy,
      prevalence estimates for stage 3 to 5 CKD are around 4 million yet, less than 30%
      of these subjects are believed to be followed at nephrology clinics. This means
      that in Italy for every dialyzed patient there are about 85 individuals with
      possibly progressive kidney disease, while fewer than five (mainly stage 4 and 5
      patients) are actually followed by a nephrologist.

PMID- 18828127
TI  - [Collaboration between nephrologists, cardiologists and diabetologists and the
      importance of early diagnosis of chronic kidney disease].
AB  - The incidence and prevalence of kidney disorders is high in patients with cardiac
      disease or diabetes, and this requires close collaboration between nephrologists,
      cardiologists and diabetologists. Renal function disorders and signs of kidney
      disease have been demonstrated to be independent cardiovascular risk factors. At
      the same time, even very initial reductions of renal function have been shown to
      be an independent risk factor for cardiovascular death. Diagnosing progressive
      renal disease and chronic kidney disease at an early stage is thus very
      important. Thanks to interspecialist collaboration, early diagnosis will delay
      the progression of renal disease and reduce the associated cardiovascular risk.
      As regards chronic kidney disease and other diabetic complications, the need for
      early diagnosis is linked to their high costs for patients, society, and health
      care organizations. Micro- and macroalbuminuria are well-known independent risk
      factors both for chronic kidney disease and cardiovascular disease. Thus,
      reducing albuminuria should be considered a crucial goal in the treatment and
      secondary prevention of progressive renal disease.

PMID- 18828128
TI  - [Objectives of the low-protein diet].
AB  - The prescription of low-protein diets to patients with chronic kidney disease has
      several objectives: to lower the dietary phosphorus load and circulating
      phosphorus and parathyroid hormone levels, and to improve the acid-base control
      and uremic symptoms while preserving the nutritional status. However, such
      objectives are always subordinate to the necessity of maintaining adequate
      calorie intake. An important target of any reduction of dietary protein intake is
      the delay of renal death and start of dialysis, as demonstrated by several
      methodologically sound studies and meta-analyses. However, no prospective study
      has yet confirmed the nephroprotective potential of low-protein diets repeatedly
      shown in animal models. Such negative results in human studies could be explained
      by their frequent methodological flaws, as well as by the modest actual reduction
      of protein intake compared with pre-study levels. The recent Cochrane meta
      analysis confirmed that reducing dietary protein intake can delay renal death and
      dialysis. The Number-to-Treat estimate in the Cochrane meta-analysis (NNT=16) was
      even better than similar estimates in the statin prevention trials ''4S'' and
      ''WOSCOPS''.

PMID- 18828129
TI  - [Low-protein diet and proteinuria].
AB  - Proteinuria has a direct toxic effect on the kidney and is a predictor of renal
      disease progression and outcome also in nondiabetic patients. Controlling
      proteinuria by reducing the dietary protein intake slows the progression of renal
      damage, as has been demonstrated in many experimental and clinical studies with
      low-protein diets (LPD). Serum albumin increases in LPD-treated kidney patients
      due to reduced urinary excretion. Moreover, it has been observed that LPD-treated
      kidney patients can keep an adequate nitrogen balance. Association of LPD with
      ACE inhibitors or sartans has an antiproteinuric effect stronger than that of LPD
      or antihypertensives alone, which is due to their different hemodynamic actions
      in the kidney. ACE inhibitors and sartans can be contraindicated in patients with
      stage 5 chronic kidney disease, where LPD is the only option for proteinuria
      control. Conflicting results with soy protein-based diets advise against the use
      of such diets in patients with nephrotic syndrome.

PMID- 18828130
TI  - [Altered calcium-phosphorus metabolism and low-protein diet].
AB  - Many metabolic disorders associated with uremia can affect the long-term survival
      of patients with chronic kidney disease. Such disorders can be defined as:
      hypocalcemia, increased levels of phosphorus, reduced synthesis of 1,25
      dihydroxyvitamin D and serum calcitriol, and reduced expression of vitamin D
      receptors on parathyroid cells with increased parathyroid hormone levels and
      secondary hyperparathyroidism. Phosphorus, which plays a crucial role in the
      progression of progressive renal disease, has been shown to be an independent
      risk factor for death in hemodialysis patients. Thus, reducing the phosphorus
      intake by decreasing dietary proteins may slow the progression of renal disease.
      Hypocalcemia is typically associated with chronic kidney disease. It is due to
      the reduced intestinal absorption of calcium and the spontaneously reduced
      protein intake that occur in patients with progressive renal disorders. Activated
      vitamin D and calcium supplements should be administered to patients who are
      following low-protein diets to prevent secondary hyperparathyroidism; the doses
      should be correlated with actual renal function and protein intake.

PMID- 18828131
TI  - [Relationship between low-protein diet and hypertension control].
AB  - Arterial hypertension is found in almost all patients with chronic kidney
      disease. The US Kidney Foundation guidelines recommend a pressure target for
      chronic kidney disease patients (130/80 mmHg) that may be difficult to reach
      because of the reduced sodium excretion in these patients and the widespread use
      of vasodilator drugs. Reducing the dietary protein intake may help to lower the
      dietary sodium load. The 130/80 mmHg target has been reached in 30% of stage 4
      and 5 patients only after six months of a very low-protein diet supplemented with
      keto-analogues and essential amino acids. However, even moderate reductions of
      dietary sodium intake are useful in patients with compromised renal function, as
      was shown by Koomans et al more than 20 years ago. Blood pressure levels are
      lower in vegetarians, possibly also because of the reduced sodium content of
      potassium-rich vegetarian diets. Diets rich in unrefined cereals, vegetables,
      fruit and low-fat cheese may be useful in patients with chronic kidney disease.
      Commercial low-protein preparations may help to design diets that are both low in
      sodium, potassium and phosphorus and adequate for caloric needs.

PMID- 18828132
TI  - [Definition of the nutritional therapy in the conservative treatment of chronic
      kidney disease].
AB  - Nutritional therapy has a leading role in the conservative treatment of chronic
      kidney disease (CKD). In the context of CKD, nutritional therapy means designing
      diets to reduce the patient's intake of proteins, phosphorus and sodium, while
      preserving adequate energy intake. Nutritional therapy may require also
      supplementation with calcium carbonate, iron, or essential amino acids and keto
      acids. Different nutritional strategies can be devised according to the protein
      needs of CKD patients: diets with controlled protein intake (protein RDA: 0.8
      g/kg/day); low-protein and low-phosphorus diets (protein: 0.6 g/kg/day,
      phosphorus: 500-700 mg/day); very low-protein and low-phosphorus diets (protein:
      0.3 g/kg/day, phosphorus: 300-400 mg/day). Much of the protein intake should be
      of high biological value (e.g., 0.4 g/kg/day of 0.6 g/kg/day or supplementation
      with essential amino acids and keto acids is needed). The sodium chloride content
      of low-protein and very low-protein diets should be kept between 2 and 5 g/day
      according to individual needs, and the energy intake should be kept at 30 to 35
      kcal/kg/day.

PMID- 18828133
TI  - [Low-protein diet and nutritional status].
AB  - Low-protein diets (LPDs) are most useful to control uremic symptoms, but the fear
      of malnutrition is still an issue. Thanks to commercially available low-protein
      preparations, reducing the protein intake to 0.6 mg/kg/day and even 0.3 mg/kg/day
      (very low-protein diets, VLPDs) is quite easy. However, providing palatable low
      protein diets without disrupting the patient's lifestyle may not be as easy as
      reducing the protein intake. The risk is a low compliance with the dietary
      prescription, resulting in reduction of calorie intake and malnutrition. The risk
      is even higher in patients beginning dialysis, for some degree of malnutrition is
      frequent in such subjects. Preserving an adequate nutritional situation is
      feasible for a long time in LPD-treated and VLPD-treated kidney patients
      independently of age and diabetes, as demonstrated by the MDRD study. Careful
      follow-up of protein and calorie intake as well as nutritional status is,
      however, required. Several anthropometric, laboratory, clinical, and
      bioelectrical impedance indices are available for follow-up. Moderate yet steady
      physical activity is highly advisable in patients with progressive renal disease.

PMID- 18828134
TI  - [Compliance with low-protein diet in patients with chronic kidney disease].
AB  - Direct evaluation of the compliance with nutritional therapy is possible only in
      clinical trials while indirect methods such as self-reporting and interviews are
      used in clinical practice. Dietary history is the best method to evaluate
      nutritional habits in clinical practice; the same holds true for the compliance
      with low-protein diets in patients with chronic kidney disease. Other indexes to
      assess dietary compliance should be simple and easy to use in the clinical
      practice. Some of such functional and biological markers are blood urea nitrogen
      and serum phosphate levels (indirect markers of dietary intake), weight and body
      mass index (indirect markers of energy intake), and daily urinary excretion of
      nitrogen and sodium (indirect markers of protein and salt intake). The compliance
      with a low-protein diet in patients with chronic kidney disease is strongly
      influenced by psychosocial factors (e.g., satisfaction and comprehension), and
      thus by the supporting role of the physician and the dietitian, but also by the
      level of renal function and food characteristics. It must be pointed out that
      even a protein intake reduction of 0.2 g/kg/day improves blood urea nitrogen,
      phosphate levels, and acidosis.

PMID- 18828135
TI  - [Socioeconomic aspects of dialysis treatment].
AB  - The Italian research institute CENSIS recently estimated that the total monetary
      cost of dialysis in Italy reached almost 2,700 billion old lira (about 1.4
      billion euros), with more than a quarter of that as social costs largely borne by
      families. The yearly cost in Italy for acetate and bicarbonate dialysis has been
      estimated at Euro 35,000 per patient and is steadily rising. Delaying renal death
      and start of dialysis by an average of two years is one of the most relevant
      ''monetary'' benefits of low-protein diets, even more so when considering that
      about half of all elderly patients starting dialytic treatment will die within
      three years. Reduced intake of phosphorus is another benefit of low-protein
      therapies that is associated with substantial monetary savings, thanks to a
      reduced need for phosphate-binding agents. Highly palatable preparations of low
      protein content are already available, and are probably already self-paying if
      the savings from reduced prescription of phosphate binders are accounted for.

PMID- 18828136
TI  - [Low-protein diet in Italy today: the conclusions of the Working Group from the
      Italian Society of Nephrology].
AB  - The high estimated prevalence of chronic kidney disease (CKD) forcefully supports
      the need for collaboration among nephrologists, cardiologists, diabetologists and
      general practitioners, to reduce the cardiovascular risk of CKD patients and
      delay the start of dialysis. Many studies confirm that reducing the dietary
      intake of proteins improves uremia as well as acid-base and phosphorus disorders
      without exposing the CKD patient to the risk of malnutrition. The possibility of
      delaying renal death and the start of dialysis by almost one to two years is also
      recognized, thanks in part to the antiproteinuric effect of low-protein diets
      supplemented with keto acids and essential amino acids. Reducing the dietary
      protein intake delays the start of dialysis independently of the effect of renin
      angiotensin system (RAS)-active antihypertensive drugs. Reduction of the dietary
      protein intake is indicated in patients with a glomerular filtration rate <25
      mL/min (CKD stages 4 and 5). Some situations may, however, require an earlier
      switch to a low-protein diet, e.g., high proteinuria, renal function worsening at
      more than 5 mL/min/year, diabetes, and metabolic decompensation. If well designed
      and properly carried out, reduction of the dietary intake of proteins is not
      associated with low serum albumin levels or malnutrition, and does not affect
      patients death. Today, highly palatable, high-quality reduced protein
      preparations are widely available to reduce the protein intake of CKD patients.

PMID- 18828138
TI  - Immunoprevalence of the CD4+ T-cell response to HIV Tat and Vpr proteins is
      provided by clustered and disperse epitopes, respectively.
AB  - Recent studies have suggested including nonstructural proteins as Tat and Vpr in
      HIV vaccines. However, little is known about the CD4+ T-cell response that these
      small proteins induce in humans. We have therefore evaluated these responses by
      in vitro priming experiments of CD4+ T lymphocytes harvested in healthy donors.
      In the Tat protein, only one peptide primed CD4+ T cells of eight HLA unrelated
      healthy donors. T cells induced by this peptide recognized immature DC loaded
      with the native Tat protein and are restricted by multiple HLA-DR molecules, in
      agreement with its binding capacity. This peptide was therefore processed in an
      appropriate manner and was highly immunoprevalent. CD4+ T-cell response to Vpr
      peptides was more disperse and involved six different peptides depending on the
      HLA-DR molecules of the donors. Two overlapping peptides were T-cell stimulating
      in at least half of the donors. T-cell response to Vpr in multiple donors is the
      result of a combination of several CD4+ T-cell epitopes with good to moderate
      immunoprevalence. Altogether, our results show that the frequency of responders
      to HIV Tat or Vpr proteins relies on one or multiple CD4+ T-cell epitopes,
      respectively.

PMID- 18828139
TI  - NKT cell development in the absence of the autoimmune regulator gene (Aire).
AB  - Autoimmune regulator gene (Aire)-deficient mice develop an array of autoimmune
      lesions that reflect failures of immune tolerance. Negative selection is clearly
      compromised in these mice, but there is evidence to suggest that other mechanisms
      of tolerance might also be affected, including a possible impairment of
      regulatory T cell (Treg) development. Studies to date have failed to demonstrate
      any significant impact on the development or function of the FOXP3+ Treg
      compartment, but NKT cells represent a distinct regulatory cell lineage that also
      develop in the thymus and which are known to influence self-tolerance. Aire
      related defects coincide with NKT cell deficiencies in a number of animal models,
      but the direct consequence of Aire-deficiency on NKT cell development has not
      been established. In this study, we demonstrate that the frequency, distribution
      and cytokine production of NKT cells and their subsets is principally normal in
      Aire-deficient mice. We conclude that Aire has little or no effect on regulatory
      T cell development in general and NKT cells in particular.

PMID- 18828141
TI  - A controlled trial of a school-based Internet program for reducing depressive
      symptoms in adolescent girls.
AB  - BACKGROUND: This study evaluates the benefits of a self-directed Internet
      intervention for depression (MoodGYM) delivered as a part of the high school
      curriculum. METHOD: One hundred and fifty-seven girls, aged 15 and 16 years, were
      allocated to undertake either MoodGYM or their usual curriculum. MoodGYM's impact
      on depressive symptoms, risk of depression, attributional style, depression
      literacy and attitudes toward depression was examined using random effect
      regression. RESULTS: MoodGYM produced a significantly faster rate of decline in
      depressive symptoms over the trial period than the control condition. The effect
      size for MoodGYM was not significant immediately after the intervention (Cohen's
      d=.19, 95% CI -.18-.56) but was moderate and significant 20 weeks after the
      intervention (d=.46, 95% CI .10-.82). Girls with high depression scores before
      intervention showed the strongest benefits on self-reported depression at follow
      up (d=.92, 95% CI .10-1.38). There were no significant intervention effects on
      depression status, attributional style, depression literacy, and attitudes.
      Approximately 70% of girls in the MoodGYM group completed less than three of its
      modules and completion of fewer modules was related to high depression score
      before intervention. CONCLUSIONS: The findings suggest that there are benefits
      from MoodGYM on self-reported depressive symptoms but has low rates of completion
      highlight problems in ensuring adherence to Internet programs for depression.

PMID- 18828142
TI  - Neural alterations associated with anxiety symptoms in obstructive sleep apnea
      syndrome.
AB  - BACKGROUND: Neuropsychological comorbidities, including anxiety symptoms,
      accompany obstructive sleep apnea (OSA); structural and functional brain
      alterations also occur in the syndrome. The objective was to determine whether
      OSA patients expressing anxiety symptoms show injury in specific brain sites.
      METHODS: Magnetic resonance T2-relaxometry was performed in 46 OSA and 66 control
      subjects. Anxiety symptoms were evaluated using the Beck Anxiety Inventory (BAI);
      subjects with BAI scores >9 were classified anxious. Whole brain T2-relaxation
      maps were compared between anxious and nonanxious groups using analysis of
      covariance (covariates, age and gender). RESULTS: Sixteen OSA and seven control
      subjects showed anxiety symptoms, and 30 OSA and 59 controls were nonanxious.
      Significantly higher T2-relaxation values, indicating tissue injury, appeared in
      anxious OSA versus nonanxious OSA subjects in subgenu, anterior, and mid
      cingulate, ventral medial prefrontal and bilateral insular cortices, hippocampus
      extending to amygdala and temporal, and bilateral parietal cortices. Brain injury
      emerged in anxious OSA versus nonanxious controls in bilateral insular cortices,
      caudate nuclei, anterior fornix, anterior thalamus, internal capsule, mid
      hippocampus, dorsotemporal, dorsofrontal, ventral medial prefrontal, and parietal
      cortices. CONCLUSIONS: Anxious OSA subjects showed injury in brain areas
      regulating emotion, with several regions lying outside structures affected by OSA
      alone, suggesting additional injurious processes in anxious OSA subjects.

PMID- 18828144
TI  - Nanoscale organization of CD4 molecules of human T helper cell mapped by NSOM and
      quantum dots.
AB  - CD4 molecule, the surface marker of T helper cell, has been confirmed to be the
      main cellular receptor for the human immunodeficiency viruses HIV-1, HIV-2 and
      SIV. Recent research demonstrated the importance of the spatial arrangement of
      CD4 on the cell membrane to its binding efficiency to virus. In this article, the
      combined near-field scanning optical microscopy (NSOM) and quantum dots (QDs)
      fluorescent labeling technology were performed to investigate the nanoscale
      organization of CD4 molecules with a spatial resolution about 100 nm.
      Simultaneous topographic image of the T helper cell and fluorescent image of QDs
      have been directly gained by NSOM/QDs-based system. Intensity- and size
      distribution histograms of the QDs fluorescent spots verify that approximately
      80% of the CD4 molecules are organized in nanosized domains randomly distributed
      on the cell surface. Intensity-size correlation analysis revealed heterogeneity
      in the molecular packing density of the domains. Our results also illustrated the
      combination of NSOM imaging and QDs labeling is an ultrasensitive, high
      resolution technique to probe nanoscale organization of molecules on the cell
      surface.

PMID- 18828143
TI  - The phenomenology of bipolar disorder: what drives the high rate of medical
      burden and determines long-term prognosis?
AB  - Bipolar disorder (BD) has been classically described as one of episodic mood
      disturbances. New evidence suggests that a chronic course and multisystem
      involvement is the rule, rather than the exception, and that together with
      disturbances of circadian rhythms, mood instability, cognitive impairment, a high
      rate of medical burden is often observed. The current diagnostic approach for BD
      neither describes the multisystem involvement that the recent literature has
      highlighted nor points toward potential predictors of long- term outcome. In
      light of the new evidence that the long-term course of BD is associated with a
      high prevalence of psychiatric comorbidity and an increased mortality from
      medical disease, we propose a multidimensional approach that includes several
      symptom domains, namely affective instability, circadian rhythm dysregulation,
      and cognitive and executive dysfunction, presenting in various combinations that
      give shape to each individual presentation, and offers potential indicators of
      overall long-term prognosis.

PMID- 18828145
TI  - Infant mortality following male takeovers in wild geladas.
AB  - Since Sugiyama's [1965] first observations of infanticide, empirical evidence
      from a multitude of primate species has supported the sexual selection hypothesis
      the idea that males enhance their reproductive success by killing nonrelated,
      unweaned infants to hasten the mothers' return to fertility. Like other primates
      that live in social groups where paternity certainty is high, the social
      structure of geladas [Theropithecus gelada] suggests that infanticide by males
      could enhance their reproductive success. Nevertheless, empirical evidence for
      infanticide in this species is limited to anecdotal accounts. Using the timing of
      infant mortality and female reproductive and behavioral data collected across 26
      months from a population of geladas living in the Simien Mountains National Park,
      Ethiopia, we test whether sexually selected infanticide occurs in this species.
      We also examine two additional hypotheses [noninfanticide hypothesis and
      generalized aggression hypothesis] for this population. Results suggest that
      sexually selected infanticide in geladas may, indeed, be a threat to females with
      dependent infants. First, male takeovers-the most likely time for infanticide
      were associated with subsequently elevated rates of infant death [a 32-fold
      increase] comprising nearly 60% of all infant mortality. Second, females who lost
      infants during this period returned to fertility more quickly than if infants had
      lived [IBIs were 50% shorter], and third, all of these females were observed to
      mate with the new male. We found little to no support for other hypotheses.
      Finally, these results raise the possibility that anecdotal reports [from
      previous studies and this study] of pregnancy termination, accelerated weaning,
      and deceptive sexual swellings may represent female counterstrategies to male
      infanticide in geladas.

PMID- 18828146
TI  - Green light stimulates somatic growth in the barfin flounder Verasper moseri.
AB  - We examined the effects of different light wavelengths-blue, green, and red-on
      the somatic growth of the barfin flounder Verasper moseri, a flatfish. The light
      sources used were fluorescent lamps and a combination of daylight and fluorescent
      lamps that produced ambient light. These light sources were filtered using blue,
      green, or red filters. During the experiments, the fish were reared in indoor
      tanks with running seawater of natural temperature and fed with commercial
      pellets twice daily until satiety. The tanks were white in color. Fish were
      exposed to constant light emitted from the fluorescent lamps (9:15, light:dark;
      08:00-17:00, light) for 14 weeks from October or September to January or to
      ambient light with a 14-week natural photoperiod from September to December. The
      wavelengths that were filtered from the fluorescent lamp light modified the
      growth of the fish, i.e., fish reared under green or blue light exhibited a
      greater total length (TL; P<0.01) and body weight (BW; P<0.01) than those reared
      under red light. In contrast, in the case of fish exposed to filtered ambient
      light, fish reared under green light exhibited a greater TL (P<0.01) and BW
      (P<0.01) than fish exposed to other wavelengths-blue-, red-, and nonfiltered
      ambient light. Our results indicate that flounder growth was modified by certain
      wavelengths, namely, green and red light, which had growth-stimulating and growth
      inhibiting effects, respectively.

PMID- 18828147
TI  - Test of the ecological-constraints model on ursine colobus monkeys (Colobus
      vellerosus) in Ghana.
AB  - For group-living mammals, the ecological-constraints model predicts that within
      group feeding competition will increase as group size increases, necessitating
      more daily travel to find food and thereby constraining group size. It provides a
      useful tool for detecting scramble competition any time it is difficult to
      determine whether or not food is limiting. We tested the ecological-constraints
      model on highly folivorous ursine colobus monkeys (Colobus vellerosus) at the
      Boabeng-Fiema Monkey Sanctuary in Ghana. Three differently sized groups were
      followed for 13 months and two others were followed for 6 months each in 2004
      2005 using focal-animal sampling and ranging scans; ecological plots and
      phenology surveys were used to determine home-range quality and food
      availability. There was relatively little difference in home-range quality,
      monthly food availability, diet, adult female ingestion rates, and rate of travel
      within food patches between the groups. However, home-range size, day-range
      length, and percent of time spent feeding all increased with group size. We
      performed a single large test of the ecological-constraints model by combining
      several separate Spearman correlations, each testing different predictions under
      the model, using Fisher's log-likelihood method. It showed that the ecological
      constraints model was supported in this study; scramble competition in this
      population is manifesting in increased ranging and time spent feeding. How costly
      this increased energy expenditure is for individuals in larger groups remains to
      be determined.

PMID- 18828148
TI  - Ground substrate affects activity budgets and hair loss in outdoor captive groups
      of rhesus macaques (Macaca mulatta).
AB  - How the captive environment influences the behavior of animals is relevant to the
      well-being of captive animals. Captivity diverges from the natural environment in
      many ways, and one goal of enrichment practices is to encourage species-typical
      behavior in these unnatural environments. This study investigated the influence
      of grass vs. gravel substrate on activity budgets and degree of hair loss in
      seven groups of captive rhesus macaques housed in outdoor enclosures at the
      California National Primate Research Center. Groups having grass substrate spent
      a greater proportion of their time foraging and a smaller proportion of time
      grooming compared with groups having gravel substrate. Increased time spent
      grooming in gravel enclosures may have contributed to significantly greater hair
      loss in those enclosures. A causal relationship between ground substrate on
      foraging and grooming, and therefore hair loss, is strengthened by similar
      changes in activity budgets and hair loss in a single group that was moved from
      gravel to grass substrate halfway through the study. These results add to growing
      evidence that substrate type in captivity is important to consider because it
      affects animal well-being. In particular, these results reveal that grass
      substrate is more effective than gravel in stimulating foraging and reducing allo
      grooming to levels that are comparable to wild populations, and enable animals to
      maintain healthier coats.

PMID- 18828149
TI  - Regression algorithm correcting for partial volume effects in arterial spin
      labeling MRI.
AB  - Partial volume effects (PVE) are a consequence of limited spatial resolution in
      brain imaging. In arterial spin labeling (ASL) MRI, the problem is exacerbated by
      the nonlinear dependency of the ASL signal on magnetization contributions from
      each tissue within an imaged voxel. We have developed an algorithm that corrects
      for PVE in ASL imaging. The algorithm is based on a model that represents the
      voxel intensity as a weighted sum of pure tissue contribution, where the
      weighting coefficients are the tissue's fractional volume in the voxel. Using
      this algorithm, we were able to estimate cerebral blood flow (CBF) for gray
      matter (GM) and white matter (WM) independently. The average voxelwise ratio of
      GM to WM CBF was approximately 3.2, in good agreement with reports in the
      literature. As proof of concept, data from PVE-corrected method were compared
      with those from the conventional, PVE-uncorrected method. As hypothesized, the
      two yielded similar CBF values for voxels containing >95% GM and differed in
      proportion with the voxels' heterogeneity. More importantly, the GM CBF assessed
      with the PVE-corrected method was independent of the voxels' heterogeneity,
      implying that estimation of flow was unaffected by PVE. An example of application
      of this algorithm in motor-activation data is also given.

PMID- 18828150
TI  - Enantiomeric differentiation of oxygenated p-menthane derivatives by 13C NMR
      using Yb(hfc)3.
AB  - The (13)C NMR behaviour of 21 p-menthanic terpene bearing an oxygenated function
      (alcohol, ketone, acetate) was examined in the presence of a chiral lanthanide
      shift reagent (Yb(hfc)(3)). For each monocyclic compound, we measured the
      lanthanide-induced shift (LIS) on the signals of the carbons and the splitting of
      signals allowing the enantiomeric differentiation. Some general features were
      found about their LIS behaviour: experimental data establishing distinct patterns
      for carvomenthone-like compounds and menthone-like compounds. The enantiomeric
      splitting was observed for the majority of signals in the spectrum of each
      compound. In the case of alcohols and acetates, the influence of the relative
      stereochemistry (cis vs trans) of isopropyl(ene) and the binding function was
      discussed.

PMID- 18828151
TI  - Complete assignments of 1H and 13C NMR spectral data for three sesquiterpenoids
      from Inula helenium.
AB  - The complete assignments of all the (1)H and (13)C NMR signals of three
      sesquiterpene lactones, 4-oxo-5(6),11-eudesmadiene-8,12-olide (1), 4-oxo-11
      eudesmaene-8,12-olide (2) and (1(10)E)-5beta-Hydroxygermacra-1(10),4(15),11-trien
      8, 12-olide (3), were carried out by various 2D NMR experiments. Compounds 1-3
      were isolated from the roots of Inula helenium for the first time. Among them, 1
      was identified as a new nor-sesquiterpene lactone, and 2 was isolated from a
      natural source for the first time. The (13)C-NMR data of compound 3 was also
      reported for the first time.

PMID- 18828152
TI  - DFT-GIAO-NBO and 13C NMR study of the delta-syn-axial effect in 2,4-disubstituted
      adamantanes.
AB  - Six groups of diastereomeric 2,4-disubstituted adamantanes were studied with DFT
      GIAO-NBO (natural orbital analysis) methods. The calculated (13)C chemical shifts
      reproduce well the experimental data. It was found that among all diastereomers,
      those bearing substituents in delta-syn-axial positions showed the largest
      overall deshielding, i.e. the sum of all (13)C chemical shifts
      [Sigmadelta((13)C)] was the greatest and also had the highest delocalization
      contribution to the molecular energy evaluated with NBO. The higher
      delocalization energy is proposed to be the origin of the deshielding delta-syn
      axial effect.

PMID- 18828153
TI  - Genotype-dependent sensitivity of hepatitis C virus to inhibitors of the p7 ion
      channel.
AB  - The hepatitis C virus (HCV) p7 protein plays a critical role during particle
      formation in cell culture and is required for virus replication in chimpanzees.
      The discovery that it displayed cation channel activity in vitro led to its
      classification within the "viroporin" family of virus-coded ion channel proteins,
      which includes the influenza A virus (IAV) M2 protein. Like M2, p7 was proposed
      as a potential target for much needed new HCV therapies, and this was supported
      by our finding that the M2 inhibitor, amantadine, blocked its activity in vitro.
      Since then, further compounds have been shown to inhibit p7 function but the
      relationship between inhibitory effects in vitro and efficacy against infectious
      virus is controversial. Here, we have sought to validate multiple p7 inhibitor
      compounds using a parallel approach combining the HCV infectious culture system
      and a rapid throughput in vitro assay for p7 function. We identify a genotype
      dependent and subtype-dependent sensitivity of HCV to p7 inhibitors, in which
      results in cell culture largely mirror the sensitivity of recombinant protein in
      vitro; thus building separate sensitivity profiles for different p7 sequences.
      Inhibition of virus entry also occurred, suggesting that p7 may be a virion
      component. Second site effects on both cellular and viral processes were
      identified for several compounds in addition to their efficacy against p7 in
      vitro. Nevertheless, for some compounds antiviral effects were specific to a
      block of ion channel function. CONCLUSION: These data validate p7 inhibitors as
      prototype therapies for chronic HCV disease. (HEPATOLOGY 2008;48:1779-1790.).

PMID- 18828154
TI  - Analysis of mutant DNA polymerase gamma in patients with mitochondrial DNA
      depletion.
AB  - We studied six unrelated children with depletion of mitochondrial DNA (mtDNA).
      They presented with Leigh syndrome, infantile hepatocerebral mtDNA depletion
      syndrome, or Alpers-Huttenlocher syndrome. Several genes have been implicated in
      mtDNA depletion. Screening of candidate genes indicated that all six patients
      were compound heterozygous for missense mutations in the gene for the catalytic
      subunit of DNA polymerase gamma (POLG). Three of the identified mutations,
      c.3328C>T (p.H1110Y), c.3401A>G (p.H1134R), and c.3406G>A (p.E1136K), have not
      been reported earlier. To investigate the functional consequences of the
      mutations, we carried out a series of biochemical assays in cultured fibroblasts.
      These studies revealed that fibroblast cultures from the patients with infantile
      hepatocerebral mtDNA depletion syndrome progressively lost their mtDNA during
      culturing, whereas fibroblast cultures from patients presenting with Leigh
      syndrome or Alpers-Huttenlocher syndrome had reduced but stable levels of mtDNA.
      DNA polymerase gamma activity was below the normal range in all patient cultures,
      except for one; however, this culture showed low levels of the heterodimeric
      enzyme and poor DNA polymerase gamma processivity. Parental fibroblast cultures
      had normal catalytic efficiency of DNA polymerase gamma, consistent with the
      observation that all carriers are asymptomatic. Thus, we report the first patient
      with Leigh syndrome caused by POLG mutations. The cell culture experiments
      established the pathogenicity of the identified POLG mutations and helped to
      define the molecular mechanisms responsible for mtDNA depletion in the patients'
      tissues. The assays may facilitate the identification of those patients in whom
      screening for POLG mutations would be most appropriate.

PMID- 18828155
TI  - Thinking about flagellar oscillation.
AB  - Bending of cilia and flagella results from sliding between the microtubular outer
      doublets, driven by dynein motor enzymes. This review reminds us that many
      questions remain to be answered before we can understand how dynein-driven
      sliding causes the oscillatory bending of cilia and flagella. Does oscillation
      require switching between two distinct, persistent modes of dynein activity? Only
      one mode, an active forward mode, has been characterized, but an alternative
      mode, either inactive or reverse, appears to be required. Does switching between
      modes use information from curvature, sliding direction, or both? Is there a
      mechanism for reciprocal inhibition? Can a localized capability for oscillatory
      sliding become self-organized to produce the metachronal phase differences
      required for bend propagation? Are interactions between adjacent dyneins
      important for regulation of oscillation and bend propagation? Cell Motil.
      Cytoskeleton 2008. (c) 2008 Wiley-Liss, Inc.

PMID- 18828156
TI  - Microarray-based genomic profiling reveals novel genomic aberrations in
      follicular lymphoma which associate with patient survival and gene expression
      status.
AB  - Follicular lymphoma (FL) is characterized by a large number of chromosomal
      aberrations. However, their exact genomic extension and involved target genes
      remain to be determined. For this purpose, we used array-based intermediate-high
      resolution genomic profiling in combination with Affymetrix gene expression
      analysis. Tumor specimens from 128 FL patients were analyzed for the presence of
      genomic aberrations and the results were correlated to clinical data sets and
      mRNA expression levels. In 114 (89%) of the 128 analyzed cases, a total of 688
      genomic aberrations (384 gains/amplifications and 304 losses) were detected.
      Frequent genomic aberrations were: -1p36 (18%), +2p15 (24%), -3q (14%), -6q
      (25%), +7p (19%), +7q (23%), +8q (14%), -9p (16%), -11q (15%), +12q (20%), -13q
      (11%), -17p (16%), +18p (18%), and +18q (28%). Critical segments of these
      imbalances were delineated to genomic fragments with a minimum size down to 0.2
      Mb. By comparison of these with mRNA gene expression data, putative candidate
      genes were identified. Moreover, we found that deletions affecting the tumor
      suppressor gene CDKN2A/B on 9p21 were detected in nontransformed FL grade I-II.
      For this aberration as well as for -6q25 and -6q26, an association with inferior
      survival was observed.

PMID- 18828157
TI  - Integrative genome-wide analysis reveals a robust genomic glioblastoma signature
      associated with copy number driving changes in gene expression.
AB  - Glioblastoma multiforme shows multiple chromosomal aberrations, the impact of
      which on gene expression remains unclear. To investigate this relationship and to
      identify putative initiating genomic events, we integrated a paired copy number
      and gene expression survey in glioblastoma using whole human genome arrays. Loci
      of recurrent copy number alterations were combined with gene expression profiles
      obtained on the same tumor samples. We identified a set of 406 "cis-acting DNA
      targeted genes" corresponding to genomic aberrations with direct copy-number
      driving changes in gene expression, defined as genes with either significantly
      concordant or correlated changes in DNA copy number and expression. Functional
      annotation revealed that these genes participate in key processes of cancer cell
      biology, providing insights into the genetic mechanisms driving glioblastoma. The
      robustness of the gene selection was validated on an external microarray data set
      including 81 glioblastomas and 23 non-neoplastic brain samples. The integration
      of array CGH and gene expression data highlights a robust cis-acting DNA targeted
      genes signature that may be critical for glioblastoma progression, with two tumor
      suppressor genes PCDH9 and STARD13 that could be involved in tumor invasiveness
      and resistance to etoposide.

PMID- 18828158
TI  - Timed sequential induction chemotherapy in AML: time for reflection.

PMID- 18828159
TI  - High-resolution genomic profiling of adenomas and carcinomas of the salivary
      glands reveals amplification, rearrangement, and fusion of HMGA2.
AB  - Carcinoma ex pleomorphic adenoma (Ca-ex-PA) is an epithelial malignancy
      developing within a benign salivary gland pleomorphic adenoma (PA). Here we have
      used genome-wide, high-resolution array-CGH, and fluorescence in situ
      hybridization to identify genes amplified in double min chromosomes and
      homogeneously staining regions in PA and Ca-ex-PA and to identify additional
      genomic imbalances characteristic of these tumor types. Ten of the 16 tumors
      analyzed showed amplification/gain of a 30-kb minimal common region, consisting
      of the 5'-part of HMGA2 (encoding the three DNA-binding domains). Coamplification
      of MDM2 was found in nine tumors. Five tumors had cryptic HMGA2-WIF1 gene fusions
      with amplification of the fusion oncogene in four tumors. Expression analysis of
      eight amplified candidate genes in 12q revealed that tumors with
      amplification/rearrangement of HMGA2 and MDM2 had significantly higher expression
      levels when compared with tumors without amplification. Analysis of individual
      HMGA2 exons showed that the expression of exons 3-5 were substantially reduced
      when compared with exons 1-2 in 9 of 10 tumors with HMGA2 activation, indicating
      that gene fusions and rearrangements of HMGA2 are common in tumors with
      amplification. In addition, recurrent amplifications/gains of 1q11-q32.1, 2p16.1
      p12, 8q12.1, 8q22-24.1, and 20, and losses of 1p21.3-p21.1, 5q23.2-q31.2, 8p,
      10q21.3, and 15q11.2 were identified. Collectively, our results identify HMGA2
      and MDM2 as amplification targets in PA and Ca-ex-PA and suggest that
      amplification of 12q genes (in particular MDM2), deletions of 5q23.2-q31.2, gains
      of 8q12.1 (PLAG1) and 8q22.1-q24.1 (MYC), and amplification of ERBB2 may be of
      importance for malignant transformation of benign PA.

PMID- 18828160
TI  - Safety and tolerability of inhaled hypertonic saline in young children with
      cystic fibrosis.
AB  - BACKGROUND: Inhaled hypertonic saline (HS) improves lung function and decreases
      pulmonary exacerbations in older patients with cystic fibrosis (CF). Initiating
      therapies in young patients has potential to preserve lung function. Before
      conducting a therapeutic trial of HS in this population, its safety must be
      evaluated and protocols for monitoring response must be tested. METHODS: We
      administered single dose 3% and 7% HS post-albuterol to 4-7 year-olds with CF
      able to perform spirometry ("preschool" group) and 4 month to 3 year-olds
      ("infant" group) using the raised volume rapid thoracoabdominal compression
      technique (RVRTC). Vital signs and cough episodes were measured after each
      inhaled treatment. RESULTS: Eight preschool subjects (mean age 5.7 +/- 0.8 years)
      and 6 infants (1.6 +/- 1.0 years) completed the 3% HS protocol, and no clinically
      important change in vital signs or decrease in FVC, FEV(1), FEV(0.5), or FEF(25
      75) occurred post-HS. Preschoolers had more cough episodes post-HS (P = 0.01).
      Seven preschoolers (6.1 +/- 0.7 years) and 8 infants (1.6 +/- 0.7 years)
      completed the 7% HS protocol. In the preschool group, FVC, FEV(0.5), and FEF(25
      75) did not change significantly. A statistically significant drop in median
      FEV(1) occurred post-7% HS attributable to a transient >20% drop in one subject.
      Infant PFT parameters were unchanged post-7% HS. Preschoolers had more cough
      episodes post-HS (P = 0.03). CONCLUSION: Acute administration of 3% and 7% HS
      appears to be safe and well-tolerated in most young children with CF. Given the
      demonstrated benefits in older patients, a therapeutic trial in this age group is
      warranted.

PMID- 18828161
TI  - Hospital medicine in high-def: importance of defining mission of hospitalist
      groups.

PMID- 18828162
TI  - The evolution and future of hospital medicine.
AB  - Hospitalists practice hospital medicine, which represents the fastest growing
      medical speciality in the history of American medicine. Initially fueled by
      research demonstrating reductions in lengths of stay and hospital costs, the
      hospitalist movement has continued to gather momentum as a response to residency
      work hour revisions, patient flow challenges in hospitals, and a growing national
      focus on patient safety. Hospitalists have expanded the clinical services they
      provide to include coverage of the critically ill, palliative care, and surgical
      co-management. Hospitalists increasingly participate in nonclinical activities as
      well, including teaching, research, quality improvement, and clinical
      informatics. Challenges remain for this new field of medicine and present
      opportunities for research and innovation. Work life satisfaction may be enhanced
      by efforts to optimize workload and redesign care delivery models. Hospitalists
      may continue to demonstrate value to stakeholders by leading efforts to improve
      quality of care, especially in areas such as interdisciplinary communication and
      smoothing patients' transitions between care settings. Hospitalists should
      continue to take an active role in improving clinical efficiency and work with
      hospitals to fully leverage the capabilities of information and telecommunication
      systems. Looking to the future, hospitalists have exciting potential for a
      positive impact in a broad range of areas and lasting effect on healthcare
      delivery.

PMID- 18828163
TI  - Economic and healthcare forces of hospitalist movement.
AB  - The field of hospital medicine has become a widely accepted model for inpatient
      care and has grown rapidly in the past ten years. The impetus for growth has
      largely been pressure to contain costs for inpatient care and improve efficiency
      in the hospital. Studies have shown that care by hospitalists is generally more
      cost-effective than care by faculty or private practice physicians without
      affecting quality. The field faces challenges in continuity of patient care and
      retention of physicians in the workforce.

PMID- 18828164
TI  - Hospitalist educators: future of inpatient internal medicine training.
AB  - Academic hospitalists have grown in number and influence over the past decade.
      This has fueled concerns about the effect of hospitalists on resident and student
      education. While the bulk of the literature favors the hospitalist teaching model
      to a more traditional model concerns remain that hospitalists may negatively
      impact housestaff autonomy and reduce exposure to subspeciality physicians. This
      paper will review the literature exploring the effect of the hospitalist teaching
      model on resident and student education.

PMID- 18828165
TI  - Achieving hospital medicine's promise through internal medicine residency
      redesign.
AB  - The promise of the hospital medicine movement is that the hospitalist model of
      care will provide better outcomes than the system it replaced. This means
      improving the quality and processes of care, reducing inefficiencies and lowering
      costs. Despite some documented improvements in these areas hospitalists have yet
      to achieve their pinnacle. These shortfalls likely result from training providers
      in residencies that have yet to evolve to address the specific needs of
      hospitalists. While most internal medicine residency training programs stress
      inpatient care they underemphasize key components of a successful hospitalist
      career. This paper overviews the state of the hospitalist movement, the current
      educational training deficiencies and the methods to deliver hospitalist-focused
      training.

PMID- 18828166
TI  - Preoperative evaluation of hospitalized patients.
AB  - Carefully managing patients undergoing elective surgeries is difficult in the
      perioperative setting. However, this becomes increasingly complex in patients
      hospitalized for acute conditions that may or may not be related to the pending
      surgery. Not only must the consulting physician take into consideration any
      complications inherent to the surgical procedure, but must also consider all
      related comorbidities of the acute condition for which the patient was initially
      hospitalized plus any existing chronic conditions. A careful systematic approach
      should be undertaken in these circumstances, which consists of (1) perioperative
      risk stratification, (2) medical optimization, and (3) perioperative risk
      reduction. Risk stratification is determined by the patient's inherent
      perioperative cardiac risk factors, whereas medical optimization and risk
      reduction are actively determined during the hospital course. For perioperative
      risk stratification, the Revised Cardiac Risk Index is the simplest tool for
      accurately identifying those patients at increased perioperative risk for cardiac
      mortality and morbidity. Medical optimization involves performing any necessary
      preoperative testing that would help identify concurrent undiagnosed medical
      conditions that might require preoperative intervention or the initiation of
      certain medication regimens to optimize disease treatment. Lastly, perioperative
      risk reduction includes any modalities that would be started to decrease the risk
      of potential perioperative cardiac, pulmonary, or other surgery-related
      comorbidities.

PMID- 18828167
TI  - Prevention of venous thromboembolism in hospitalized medical patients.
AB  - The hospitalized medical patient in the US today has multiple risk factors for
      venous thromboembolism (VTE) and is therefore at a significant risk of developing
      this condition both during hospitalization and after discharge. The American
      College of Chest Physicians (ACCP) guidelines recommend pharmacologic prophylaxis
      unless there are contraindications. Low-molecular-weight heparins (LMWH) are the
      preferred class of drugs due to multiple advantages, including daily dosing and a
      decreased risk of heparin-induced thrombocytopenia, to name a few. Several
      emerging oral anticoagulants, including Factor Xa inhibitors and direct thrombin
      inhibitors, are currently being evaluated in Phase III clinical trials as
      prophylaxis against VTE in medically ill patients and may some day replace
      parenteral drugs.

PMID- 18828168
TI  - Impact of obesity on hospitalized patients.
AB  - Obesity is increasing at an alarming rate worldwide and is a risk factor for
      cardiac disease, diabetes, and stroke. This provides a challenge for the
      physicians caring for this patient population in the hospital. Skin integrity,
      medication dosing, testing, and nutrition are all altered by obesity. We
      summarize some of the current data on caring for the obese inpatient.
      Unfortunately, few data on this unique inpatient population exist.

PMID- 18828169
TI  - Do not resuscitate does not mean do not treat: how palliative care and other
      modalities can help facilitate communication about goals of care in advanced
      illness.
AB  - A do-not-resuscitate (DNR) order is commonly used for hospitalized patients with
      advanced illness. It reflects only the desires of a patient once he or she
      suffers a full cardiopulmonary arrest. It does not reflect preferences about
      other forms of life-sustaining treatments. This article reviews the definition of
      a DNR order, describes the evidence suggesting that physicians use a DNR order in
      making determinations about other life-sustaining treatments, and will provide
      tools such as the use of palliative care consultations and combined directives in
      discussing overall goals of care.

PMID- 18828170
TI  - From "I'm not staying!" to "I'm not leaving!": ethics, communication, and empathy
      in complicated medical discharges.

PMID- 18828171
TI  - Clinical prediction rules for hospitalists.

PMID- 18828172
TI  - Translational research: forging a new cultural identity.

PMID- 18828173
TI  - The construction and characterization of two xylan-degrading chimeric enzymes.
AB  - Degradation of xylan requires several enzymes. Two chimeric enzymes, xyln-ara and
      xyln-xylo, were constructed by linking the catalytic portion of a xylanase (xyln)
      to either an arabinofuranosidase (ara) or a xylosidase (xylo) with a flexible
      peptide linker. The recombinant parental enzymes and chimeras were produced in E.
      coli at high levels and purified for characterization of their enzymatic and
      kinetic properties as well as activities on natural substrates. The chimeras
      closely resemble the parental enzymes or their mixtures with regard to protein
      properties. They share similar temperature profiles and have similar catalytic
      efficiencies as the parental enzymes when assayed using substrates 4-nitrophenyl
      alpha-L-arabinofuranoside or 2-nitrophenyl- beta-D-xylopyranoside. The chimeras
      also show unique enzymatic characteristics. In xylanase activity assays using
      Remazol Brilliant Blue-xylan, while the parental xylanase has a pH optimum of pH
      8, the chimeras showed shifted pH optima as a consequence of significantly
      increased activity at pH 6 (the optimal pH for ara and xylo). Both chimeras
      exhibited additive effects of the parental enzymes when assayed at wide ranges of
      pH and temperatures. The xyln-xylo chimera had the same activities as the
      xyln/xylo mixture in hydrolyzing the natural substrates oat spelt xylan and wheat
      arabinoxylan. Compared to the xyln/ara mixture, the xyln-ara chimera released the
      same amounts of xylose from oat spelt xylan and approximately 30% more from wheat
      arabinoxylan at pH 6. Our results demonstrate the feasibility and advantages of
      generating bifunctional enzymes for the improvement of xylan bioconversion.

PMID- 18828174
TI  - Engineering cell lines for production of replication defective HSV-1 gene therapy
      vectors.
AB  - Herpes simplex virus type 1 (HSV-1) represents an attractive vehicle for a
      variety of gene therapy applications. To render this virus safe for clinical use,
      its cytotoxic genes must be removed without losing its ability to express
      transgenes efficiently. Our vectors are deleted for the essential immediate early
      genes ICP4 and ICP27. These genes are controlled by unique promoters having
      enhancer elements responsive to a viral structural protein VP16. The expression
      of these genes occurs prior to the activation of all other lytic functions and is
      thus required to initiate and complete the virus replication cycle. For large
      scale manufacture of clinical grade vectors, efficient cell lines must be
      generated that express the essential viral gene products in trans during vector
      propagation. Here we describe methods for engineering HSV-1 production cell lines
      that improve vector growth by altering the kinetics of complementing gene
      expression. We examined the ability of Vero cells independently transduced with
      ICP4 and ICP27 under transcriptional control of their respective promoters to
      support the growth of a replication defective vector (JDTOZHE), deleted for ICP4,
      ICP27 and approximately 20 kb of internal elements that are not required for
      virus growth in Vero cells. Vector yield on this cell line was 3 logs lower than
      wild-type virus grown on Vero cells. To understand the mechanism underlying poor
      vector yield, we examined the expression of ICP4 and ICP27 during virus
      complementation. While ICP27 was expressed immediately on vector infection, the
      expression of ICP4 was considerably delayed by 8-10 h, suggesting that the ICP4
      promoter was not adequately activated by VP16 delivered by the infectious vector
      particle. Use of the ICP0 promoter to express ICP4 from the cellular genome
      resulted in higher induction levels and faster kinetics of ICP4 expression and a
      10-fold improvement in vector yield. This study suggests that vector
      complementation is highly dependent on the kinetics of complementing gene
      expression and can lead to large differences in vector yield.

PMID- 18828175
TI  - Continuous hydrogen production during fermentation of alpha-cellulose by the
      thermophillic bacterium Clostridium thermocellum.
AB  - Continuous hydrogen (H2) production during fermentation of alpha-cellulose was
      established using the thermophillic, anaerobic bacterium Clostridium thermocellum
      ATCC 27405. The objectives of this work were to characterize growth of C.
      thermocellum, quantify H2 production and determine soluble end-product synthesis
      patterns during fermentation of a cellulosic substrate under continuous culture
      conditions. A 5 L working volume fermentor was established and growth experiments
      were maintained for over 3,000 h. Substrate concentrations were varied from 1 to
      4 g/L and the feed was introduced with continuous nitrogen gas sparging to
      prevent clogging of the feed-line. The pH and temperature of the reactor were
      maintained at 7.0 and 600 degrees C, respectively, throughout the study. At
      concentrations above 4 g/L, the delivery of alpha-cellulose was impaired due to
      feed-line clogging and it became difficult to maintain a homogenous suspension.
      The highest total gas (H2 plus CO2) production rate, 56.6 mL L(-1) h(-1), was
      observed at a dilution rate of 0.042 h(-1) and substrate concentration of 4 g/L.
      Under these conditions, the H2 production rate was 5.06 mmol h(-1). Acetate and
      ethanol were the major soluble end-products, while lactate and formate were
      greatly reduced compared to production in batch cultures. Concentrations of all
      metabolites increased with increasing substrate concentration, with the exception
      of lactate. Despite a number of short-term electrical and mechanical failures
      during the testing period, the system recovered quickly, exhibiting substantial
      robustness. A carbon balance was completed to ensure that all end-products were
      accounted for, with final results indicating near 100% carbon recovery. This
      study shows that long-term, stable H2 production can be achieved during direct
      fermentation of an insoluble cellulosic substrate under continuous culture
      conditions.

PMID- 18828176
TI  - Genetic analysis of G protein-coupled receptor expression in Escherichia coli:
      inhibitory role of DnaJ on the membrane integration of the human central
      cannabinoid receptor.
AB  - The overexpression of G protein-coupled receptors (GPCRs) and of many other
      heterologous membrane proteins in simple microbial hosts, such as the bacterium
      Escherichia coli, often results in protein mistargeting, aggregation into
      inclusion bodies or cytoplasmic degradation. Furthermore, membrane protein
      production is very frequently accompanied by severe cell toxicity. In this work,
      we have employed a genetic strategy to isolate E. coli mutants that produce
      markedly increased amounts of the human central cannabinoid receptor (CB1), a
      pharmacologically significant GPCR that expresses very poorly in wild-type E.
      coli. By utilizing a CB1 fusion with the green fluorescent protein (GFP) and
      fluorescence-activated cell sorting (FACS), we screened an E. coli transposon
      library and identified an insertion in dnaJ that resulted in a large increase in
      CB1-GFP fluorescence and a dramatic enhancement in bacterial production of
      membrane-integrated CB1. Furthermore, the dnaJ::Tn5 inactivation suppressed the
      severe cytotoxicity associated with CB1 production. This revealed an unexpected
      inhibitory role of the chaperone/ co-chaperone DnaJ in the protein folding or
      membrane insertion of bacterially produced CB1. Our strategy can be easily
      adapted to identify expression bottlenecks for different GPCRs or any other
      integral membrane protein, provide useful and unanticipated mechanistic insights,
      and assist in the construction of genetically engineered E. coli strains for
      efficient heterologous membrane protein production.

PMID- 18828177
TI  - Production, purification, and characterization of human alpha1 proteinase
      inhibitor from Aspergillus niger.
AB  - Human alpha one proteinase inhibitor (alpha1-PI) was cloned and expressed in
      Aspergillus niger, filamentious fungus that can grow in defined media and can
      perform glycosylation. Submerged culture conditions were established using starch
      as carbon source, 30% dissolved oxygen concentration, pH 7.0 and 28 degrees C.
      Eight milligrams per liter of active alpha1-PI were secreted to the growth media
      in about 40 h. Controlling the protein proteolysis was found to be an important
      factor in the production. The effects of various carbon sources, pH and
      temperature on the production and stability of the protein were tested and the
      product was purified and characterized. Two molecular weights variants of the
      recombinant alpha1-PI were produced by the fungus; the difference is attributed
      to the glycosylated part of the molecule. The two glycoproteins were treated with
      PNGAse F and the released glycans were analyzed by HPAEC, MALDI/TOF-MS, NSI
      MS(n), and GC-MS. The MALDI and NSI- full MS spectra of permethylated N-glycans
      revealed that the N-glycans of both variants contain a series of high-mannose
      type glycans with 5-20 hexose units. Monosaccharide analysis showed that these
      were composed of N-acetylglucos-amine, mannose, and galactose. Linkage analysis
      revealed that the galactosyl component was in the furanoic conformation, which
      was attaching in a terminal non-reducing position. The Galactofuranose-containing
      high-mannnose type N-glycans are typical structures, which recently have been
      found as part of several glycoproteins produced by Aspergillus niger.

PMID- 18828178
TI  - A substrate-selective co-fermentation strategy with Escherichia coli produces
      lactate by simultaneously consuming xylose and glucose.
AB  - We describe a new approach for the simultaneous conversion of xylose and glucose
      sugar mixtures which potentially could be used for lignocellulosic biomass
      hydrolysate. In this study we used this approach to demonstrate the production of
      lactic acid. This process uses two substrate-selective strains of Escherichia
      coli, one which is unable to consume glucose and one which is unable to consume
      xylose. In addition to knockouts in pflB encoding for pyruvate formate lyase, the
      xylose-selective (glucose deficient) strain E. coli ALS1073 has deletions of the
      glk, ptsG, and manZ genes while the glucose-selective (xylose deficient) strain
      E. coli ALS1074 has a xylA deletion. By combining these two strains in a single
      process the xylose and glucose in a mixed sugar solution are simultaneously
      converted to lactate. Furthermore, the biomass concentrations of each strain can
      readily be adjusted in order to optimize the overall product formation. This
      approach to the utilization of mixed sugars eliminates the problem of diauxic
      growth, and provides great operational flexibility.

PMID- 18828179
TI  - Evaluation of metabolism using stoichiometry in fermentative biohydrogen.
AB  - We first constructed full stoichiometry, including cell synthesis, for glucose
      mixed-acid fermentation at different initial substrate concentrations (0.8-6 g
      glucose/L) and pH conditions (final pH 4.0-8.6), based on experimentally
      determined electron-equivalent balances. The fermentative bioH2 reactions had
      good electron closure (-9.8 to +12.7% for variations in glucose concentration and
      -3 to +2% for variations in pH), and C, H, and O errors were below 1%. From the
      stoichiometry, we computed the ATP yield based on known fermentation pathways.
      Glucose-variation tests (final pH 4.2-5.1) gave a consistent fermentation pattern
      of acetate + butyrate + large H2, while pH significantly shifted the catabolic
      pattern: acetate + butyrate + large H2 at final pH 4.0, acetate + ethanol +
      modest H2 at final pH 6.8, and acetate + lactate + trivial H2 at final pH 8.6.
      When lactate or propionate was a dominant soluble end product, the H2 yield was
      very low, which is in agreement with the theory that reduced ferredoxin (Fd(red))
      formation is required for proton reduction to H2. Also consistent with this
      hypothesis is that high H2 production correlated with a high ratio of butyrate to
      acetate. Biomass was not a dominant sink for electron equivalents in H2
      formation, but became significant (12%) for the lowest glucose concentration
      (i.e., the most oligotrophic condition). The fermenting bacteria conserved energy
      similarly at approximately 3 mol ATP/mol glucose (except 0.8 g-glucose/L, which
      had approximately 3.5 mol ATP/mol glucose) over a wide range of H2 production.
      The observed biomass yield did not correlate with ATP conservation; low observed
      biomass yields probably were caused by accelerated rates of decay or production
      of soluble microbial products.

PMID- 18828180
TI  - Molecular studies of rheumatoid factor using pseudobioaffinity membrane
      chromatography.
AB  - Using pseudobioaffinity ligand L-histidine immobilized to poly(ethylene vinyl
      alcohol) hollow fiber membrane is an interesting approach for the purification of
      total IgG and its subclasses from untreated serum in a single step. Gentle
      adsorption and elution conditions of this chromatography system allow efficient
      recovery of the protein in its native form. This approach was employed for the
      recovery and molecular study of rheumatoid factor (RF), an anti-IgG autoantibody
      (AAb) that form immune complexes with autologous IgG Abs in the sera. The purity
      of the recovered molecule was analyzed on sodium dodecyl sulfate-polyacrylamide
      gel electrophoresis (SDS-PAGE), revealed a 150-kDa IgG band and an additional
      approximately 300 kDa band which may be RF bound IgG complex. Since RF is an AAb,
      the purified protein was studied for its catalytic functions like peptide, DNA,
      and RNA hydrolyzing activities. The substrate Pro-Phe-Arg-4-methyl-coumaryl-7
      amide (PFR-MCA) hydrolyzing activity by total IgG from different patient sera was
      found to be greater than healthy controls. In an effort to identify the subclass
      specificity for the proteolytic function, the pre-purified total IgG fractions
      from rheumatoid arthritis (RA) sera were subjected to rechromatography using a
      discriminating buffer. In this experiment, the activity was found in the non
      retained fractions suggesting IgG2 specificity for the catalytic function. A
      comparative study between different catalytic functions was performed for IgG
      separated from individual patient.

PMID- 18828181
TI  - Reducing emergency department visits for ear pain.

PMID- 18828182
TI  - Resources: free TV turnoff week poster--last call!

PMID- 18828183
TI  - Salty snacks and obesity--an unexpected link?

PMID- 18828184
TI  - Protecting the environment--and protecting children from mercury exposure.

PMID- 18828185
TI  - Medicines in kids: don't think of kids as small adults....

PMID- 18828186
TI  - . . . Maybe they can be avoided in some kids with reflux....

PMID- 18828187
TI  - . . . Why do placebos work in some kids with migraine. . . .

PMID- 18828188
TI  - . . . And what about medicines in our drinking water?

PMID- 18828189
TI  - Emerging Science in Pulp Therapy: New Insights into Dilemmas and Controversies.
      Proceedings of a symposium, November 2-3, 2007, Chicago, Illinois, USA.

PMID- 18828190
TI  - Emerging Science in Pulp Therapy: New Insights into Dilemmas and Controversies.
      Proceedings of a symposium, November 2-3, 2007, Chicago, Illinois, USA.

PMID- 18828191
TI  - The uncrowded window of object recognition.
AB  - It is now emerging that vision is usually limited by object spacing rather than
      size. The visual system recognizes an object by detecting and then combining its
      features. 'Crowding' occurs when objects are too close together and features from
      several objects are combined into a jumbled percept. Here, we review the
      explosion of studies on crowding--in grating discrimination, letter and face
      recognition, visual search, selective attention, and reading--and find a
      universal principle, the Bouma law. The critical spacing required to prevent
      crowding is equal for all objects, although the effect is weaker between
      dissimilar objects. Furthermore, critical spacing at the cortex is independent of
      object position, and critical spacing at the visual field is proportional to
      object distance from fixation. The region where object spacing exceeds critical
      spacing is the 'uncrowded window'. Observers cannot recognize objects outside of
      this window and its size limits the speed of reading and search.

PMID- 18828192
TI  - Fetal outcomes of critically ill pregnant women admitted to the intensive care
      unit for nonobstetric causes.
AB  - INTRODUCTION: The outcome of the fetus in critically ill mothers has been briefly
      reported as a part of descriptive studies focusing on maternal risk factors for
      admission to the intensive care unit. We evaluated the risk factors for adverse
      fetal outcomes in critically ill pregnant women admitted to the intensive care
      unit for nonobstetrical reasons. DESIGN: Retrospective cohort study of all
      critically ill pregnant patients >18 yr; admitted to four (medical, surgical,
      trauma, and mixed medical-surgical) intensive care units at the Mayo Clinic in
      Rochester, MN; during the period of January 1995 to December 2005. Only pregnant
      women admitted to the intensive care unit in the antepartum period for
      nonobstetrical indications were included. Main predictors for fetal outcomes
      included: maternal comorbidities, obstetrical history, intensive care unit
      interventions, and intensive care unit complications. Fetal outcomes were defined
      as spontaneous abortions, neonatal mortality, fetal deaths, admission to the
      neonatal intensive care unit, neonatal intensive care unit length of stay, and
      neonatal intensive care unit complications. RESULTS: A total of 153 adult women
      (>18 yr) with a diagnosis of pregnancy were admitted to the intensive care unit,
      of whom 93 pregnant women met the inclusion criteria. Median maternal age was 26
      yr (interquartile range 22-33) and median gestational age was 25 wk
      (interquartile range 8-33). The median maternal Acute Physiologic and Chronic
      Health Evaluation III score was 27 (interquartile range 17-38). There were 32
      fetal losses; 18 were spontaneous abortions and 14 were fetal deaths. Ten
      neonates required neonatal intensive care unit admission, five for respiratory
      distress syndrome; and only one neonate died. The median neonatal intensive care
      unit length of stay was 34 days (interquartile range 15-87). After multivariable
      logistic regression analysis, the risk factors associated with fetal loss were:
      presence of maternal shock, odds ratio 6.85 (95% confidence interval 1.16-58, p =
      0.04); maternal transfusion of blood products, odds ratio 7.24 (95% confidence
      interval 1.4-49, p = 0.02); and gestational age, odds ratio 1.2 for every
      gestational week below 37 wk (95% confidence interval 1.1-1.3, p < 0.001).
      CONCLUSIONS: Nonobstetrical critical illness in pregnant women significantly
      affects fetal and neonatal outcomes. Maternal shock, maternal requirement of
      allogenic blood product transfusion and lower gestational age were associated
      with an increased risk of fetal loss.

PMID- 18828194
TI  - Variation in the myosin light chain kinase gene is associated with development of
      acute lung injury after major trauma.
AB  - BACKGROUND: Single nucleotide polymorphisms in the myosin light chain kinase
      (MYLK) gene have been implicated in the risk of sepsis-related acute lung injury
      and asthma. MYLK encodes protein isoforms involved in multiple components of the
      inflammatory response, including apoptosis, vascular permeability, and leukocyte
      diapedesis. We tested the association of MYLK gene variation in the development
      of acute lung injury in major trauma patients. METHODS: We conducted a
      prospective cohort study of 273 subjects with major trauma (injury severity score
      > or = 16). All x-rays and clinical data were reviewed by three clinicians for
      acute lung injury classification. A total of 17 tagging single nucleotide
      polymorphisms in MYLK were genotyped. Single nucleotide polymorphisms were
      individually assessed at the genotype level, and multiple logistic regression
      models were used to adjust for baseline variables. Haplotype analyses of sliding
      windows including 2-5 single nucleotide polymorphisms were conducted. RESULTS:
      Ninety-one of the 273 subjects (33%) met criteria for acute lung injury within 5
      days of traumatic insult. Three informative MYLK coding single nucleotide
      polymorphisms were individually associated with acute lung injury, with two
      informative risk-conferring genotypes His21Pro (CC genotype, odds ratio = 1.87,
      95% confidence interval 1.06-3.33; p = 0.022) and Pro147Ser (TT, odds ratio =
      2.13, 95% confidence interval 1.14-4.10; p = 0.011) more frequent than the
      noninformative Thr335Thr CC genotype (odds ratio = 0.42, 95% confidence interval
      0.20-0.85; p = 0.010). Each of these genotypic associations was more pronounced
      in African Americans with trauma. Multivariate analyses demonstrated the
      association of each MYLK single nucleotide polymorphism with acute lung injury to
      be independent of age, injury severity score, Acute Physiology and Chronic Health
      Evaluation III, and the mechanism of trauma. Finally, haplotype analyses revealed
      strong acute lung injury associations with 2-4 single nucleotide polymorphism
      haplotypes, all involving His21Pro (p < 0.008). CONCLUSIONS: Three MYLK coding
      single nucleotide polymorphisms previously associated with sepsis-induced acute
      lung injury and severe asthma in African Americans were associated with acute
      lung injury development after trauma in African Americans, although effect
      directions differed. These results confirm our prior studies implicating MYLK as
      a susceptibility gene in a distinct acute lung injury subset other than sepsis.

PMID- 18828193
TI  - Multicenter implementation of a consensus-developed, evidence-based, spontaneous
      breathing trial protocol.
AB  - OBJECTIVE: Evidence-based practice recommendations abound, but implementation is
      often unstructured and poorly audited. We assessed the ability of a peer network
      to implement an evidence-based best practice protocol and to measure patient
      outcomes. DESIGN: Consensus definition of spontaneous breathing trial followed by
      implementation in eight academic medical centers. SETTING: Six medical, two
      surgical, and two combined medical/surgical adult intensive care units among
      eight academic medical centers. STUDY POPULATION: Patients initiating mechanical
      ventilation through an endotracheal tube during a 12-wk interval formed the study
      population. INTERVENTIONS: Adoption and implementation of a common spontaneous
      breathing trial protocol across multiple intensive care units. MEASUREMENTS AND
      MAIN RESULTS: Seven hundred five patients had 3,486 safety screens for conducting
      a spontaneous breathing trial; 2072 (59%) patients failed the safety screen.
      Another 379 (11%) patients failed a 2-min tolerance screen and 1,122 (34%)
      patients had a full 30-120 min spontaneous breathing trial performed. Seventy
      percent of eligible patients were enrolled. Only 55% of passing spontaneous
      breathing trials resulted in liberation from mechanical ventilatory support
      before another spontaneous breathing trial was performed. CONCLUSIONS: Peer
      networks can be effective in promoting and implementing evidence-based best
      practices. Implementation of a best practice (spontaneous breathing trial) may be
      necessary for, but by itself insufficient to achieve, consistent and timely
      liberation from ventilator support.

PMID- 18828195
TI  - Ciglitazone ameliorates lung inflammation by modulating the inhibitor kappaB
      protein kinase/nuclear factor-kappaB pathway after hemorrhagic shock.
AB  - OBJECTIVE: Peroxisome proliferator-activated receptor-gamma is a ligand-activated
      transcription factor. Ciglitazone, a peroxisome proliferator-activated receptor
      gamma ligand, has been shown to provide beneficial effects in experimental models
      of sepsis and ischemia/reperfusion injury. We investigated the effects of
      ciglitazone on lung inflammation after severe hemorrhage. DESIGN: Prospective,
      laboratory study, rodent model of hemorrhagic shock. SETTING: University hospital
      laboratory. SUBJECTS: Male rats. INTERVENTIONS: Hemorrhagic shock was induced by
      withdrawing blood to a mean arterial pressure of 50 mm Hg. At 3 hrs after
      hemorrhage, rats were rapidly resuscitated by returning their shed blood. At the
      time of resuscitation and every hour thereafter, animals received ciglitazone (10
      mg/kg) or vehicle intraperitoneally. Heart rate and mean arterial pressure were
      measured throughout the experiment. Plasma and lung tissue were collected for
      analysis up to 3 hrs after resuscitation. MEASUREMENTS AND MAIN RESULTS:
      Ciglitazone treatment ameliorated mean arterial pressure, reduced lung injury,
      significantly blunted lung neutrophil infiltration, and lowered plasma
      interleukin-6, interleukin-10, and monocyte chemoattractant protein-1 levels. In
      a time course analysis, vehicle-treated rats had a significant increase in
      nuclear factor-kappaB DNA binding, which was preceded by increased inhibitor
      kappaB protein kinase activity and inhibitor kappaB alpha degradation in the
      lung. Treatment with ciglitazone significantly reduced inhibitor kappaB protein
      kinase activity and inhibitor kappaB alpha degradation and completely inhibited
      nuclear factor-kappaB DNA binding. This reduction of inhibitor kappaB protein
      kinase activity afforded by ciglitazone appeared to be a consequence of a
      physical interaction between peroxisome proliferator-activated receptor-gamma and
      increased inhibitor kappaB protein kinase. CONCLUSION: Ciglitazone ameliorates
      the inflammatory response and may reduce lung injury after hemorrhagic shock.
      These protective effects appear to be mediated through inhibition of the
      inhibitor kappaB protein kinase/nuclear factor-kappaB pathway.

PMID- 18828196
TI  - Intensive plasma exchange increases a disintegrin and metalloprotease with
      thrombospondin motifs-13 activity and reverses organ dysfunction in children with
      thrombocytopenia-associated multiple organ failure.
AB  - BACKGROUND: Thrombocytopenia-associated multiple organ failure (TAMOF) is a
      poorly understood syndrome in critically ill children. A disintegrin and
      metalloprotease with thrombospondin motifs (ADAMTS-13), formerly known as von
      Willebrand factor (VWF) cleaving protease, is decreased in adults with VWF
      mediated thrombotic microangiopathy, and intensive plasma exchange (PEx) both
      replenishes ADAMTS-13 and improves outcome in these patients. OBJECTIVES: To
      determine whether: 1) critically ill children with TAMOF syndrome have decreased
      ADAMTS-13 activity, 2) ADAMTS-13 activity correlates with platelet counts and VWF
      antigen, 3) the autopsies from patients who died with reduced ADAMTS-13 activity
      have VWF-rich microthrombi, and 4) intensive PEx will restore ADAMTS-13 activity
      and facilitate organ failure resolution. DESIGN: First study: observational.
      Second study: randomized control trial. SETTING: Single center university
      pediatric intensive care unit. PATIENTS: First study: thirty-seven consecutive
      children (17 males and 20 females; ages ranging from 9 days to 23 years)
      identified with > or = 2 organs dysfunction were enrolled. Seventy-six percent of
      these children had thrombocytopenia (platelet counts < 100,000/mm3). Five
      additional critically ill children without MOF were also enrolled. In the second
      study, children with severe TAMOF (platelet counts < 100,000/mm3 and > 3 organ
      failure) were randomized to PEx or standard therapy. Primary physicians and
      parents agreed to enrollment in 10 of the 20 eligible patients with ages ranging
      from 1 year to 18 years. Five patients received PEx and 5 patients received
      standard therapy. RESULTS: First study: children with TAMOF (n = 28) had
      decreased ADAMTS-13 activity, but similar plasminogen activator inhibitor-1
      activity and prothrombin time compared to children with MOF without
      thrombocytopenia (n = 9, p < 0.05). All non-survivors (n = 7) had TAMOF, reduced
      ADAMTS-13 activity, and VWF-rich microvascular thromboses at autopsy. In the
      second study, PEx (n = 5, median 12 days, 4-28 days) restored ADAMTS-13 activity
      and organ function, compared to standard therapy (n = 5, p < 0.05). CONCLUSIONS:
      Children with TAMOF syndrome can have VWF-mediated thrombotic microangiopathy.
      Similar to adult experience, PEx can replenish ADAMTS-13 activity and reverse
      organ failure.

PMID- 18828197
TI  - Efficacy and safety of mu-opioid antagonists in the treatment of opioid-induced
      bowel dysfunction: systematic review and meta-analysis of randomized controlled
      trials.
AB  - CONTEXT: Opioid-induced bowel dysfunction (OBD) is characterized by constipation,
      incomplete evacuation, bloating, and increased gastric reflux. OBD occurs both
      acutely and chronically, in multiple disease states, resulting in increased
      morbidity and reduced quality of life. OBJECTIVE: To compare the efficacy and
      safety of traditional and peripherally active opioid antagonists vs conventional
      interventions for OBD. DESIGN: We searched MEDLINE, the Cochrane Central Register
      of Controlled Trials and EMBASE. Additional reports were identified from the
      reference lists of retrieved articles. STUDY SELECTION: Studies were included if
      they were randomized controlled trials that investigated the efficacy of mu
      opioid antagonists for OBD. DATA EXTRACTION: Data were extracted by two
      independent investigators and included demographic variables, diagnoses,
      interventions, efficacy, and adverse events. RESULTS OF DATA SYNTHESIS: Twenty
      two articles met inclusion criteria and provided data on 2,352 opioid antagonist
      treated patients. The opioid antagonist investigated was alvimopan (eight
      studies), methylnaltrexone (six), naloxone (seven), and nalbuphine (one). Meta
      analysis demonstrated that methylnaltrexone and alvimopan are efficacious in
      reversing opioid-induced increased gastrointestinal transit time and
      constipation, and that alvimopan is safe and efficacious in treating
      postoperative ileus. The incidence of adverse events with opioid antagonists was
      similar to placebo and generally reported as mild-to-moderate. CONCLUSIONS:
      Insufficient evidence exists for the safety or efficacy of naloxone or nalbuphine
      in the treatment of OBD. Long-term efficacy and safety of any of the opioid
      antagonists is unknown, as is the incidence or nature of rare adverse events.
      Alvimopan and methylnaltrexone both show promise in treating OBD, but further
      data will be required to fully assess their place in therapy.

PMID- 18828198
TI  - Painful diabetic neuropathy: epidemiology, natural history, early diagnosis, and
      treatment options.
AB  - OBJECTIVE: To facilitate the clinician's understanding of the basis and treatment
      of painful diabetic neuropathy (PDN). BACKGROUND: PDN is one of several clinical
      syndromes in patients with diabetic peripheral neuropathy (DPN) and presents a
      major challenge for optimal management. METHODS: A systematic review of the
      literature was undertaken for articles specific to PDN, using Medline databases
      between 1966 and 2007. RESULTS: The epidemiology of PDN has not been well
      established and on the basis of available data the prevalence of pain is 10% to
      20% in patients with diabetes and from 40% to 50% in those with diabetic
      neuropathy. It has a significant impact on the quality of life and health care
      costs. Pathophysiologic mechanisms underlying PDN are similar to other
      neuropathic pain disorders and are broadly characterized as peripheral and
      central sensitization. The natural course of PDN is variable, with many patients
      experiencing spontaneous improvement and resolution of pain. Hyperglycemia
      induced pathways result in nerve dysfunction and damage, which lead to
      hyperexcitable peripheral and central pathways of pain. Glycemic control may
      prevent or partially reverse DPN and modulate PDN. Quantifying neuropathic pain
      is difficult, especially for clinical trials, although this has improved recently
      with the development of neuropathic pain-specific tools, such as the Neuropathic
      Pain Questionnaire and the Neuropathic Pain Symptom Inventory. Current
      therapeutic options are limited to symptomatic treatment and are similar to other
      types of neuropathic pain. CONCLUSIONS: A better understanding of the peripheral
      and central mechanisms resulting in PDN is likely to promote the development of
      more targeted and effective treatment.

PMID- 18828199
TI  - Predictors of change in trunk muscle strength for patients with chronic low back
      pain randomized to lumbar fusion or cognitive intervention and exercises.
AB  - OBJECTIVES: We have previously reported in two randomized controlled trials that
      cognitive intervention and exercises more effectively improved isokinetic trunk
      muscle strength than lumbar fusion and postoperative rehabilitation in patients
      with chronic low back pain. The aim of the present study was to predict changes
      in muscle strength as regard to changes in pain, function, fear-avoidance beliefs
      (self-rated questionnaires), changes in cross-sectional area and density of the
      back muscles and treatment. METHODS: We assessed 1) isokinetic trunk muscle
      strength; 2) cross-sectional area and density of back muscles by computer
      tomography (CT); and 3) pain, function, fear-avoidance beliefs, and self-
      efficacy for pain in the included patients at baseline and 1-year follow-up.
      Multiple regression analysis was performed with change in muscle strength as
      dependent variables, and changes in area/density and self-rated symptoms and
      treatment as independent variables. RESULTS: The correlations between the change
      in muscle strength and change in both cross-sectional area and density were weak
      (r < 0.1) and nonsignificant and these variables were not included in the
      multiple regression analysis. The change in pain, change in fear-avoidance
      beliefs, change in self-efficacy for pain and treatment explained 46% of the
      change in muscle strength, with change in pain and treatment as significant
      predictors. CONCLUSION: Our results emphasize the central role of pain and
      treatment for the improvements in muscle strength in patients with chronic low
      back pain.

PMID- 18828200
TI  - The Fourth National Institutes of Health Symposium on the Functional Genomics of
      Critical Injury: Surviving stress from organ systems to molecules.
AB  - Recent strides in computational biology and high-throughput technologies have
      generated considerable interest in understanding complex biological systems. The
      application of these technologies to critical illness and injury offers the
      potential to define adaptive and maladaptive programs of gene expression induced
      by infection, shock, trauma, or other inflammatory triggers, and to detect
      biomarkers and genetic polymorphisms linked to these responses and outcome. A
      systems biology approach is timely because despite substantial effort, treatment
      approaches directed at a single mediator or inflammatory pathway have met with
      little success in altering outcomes of critically ill or injured patients.
      Highlights from the Fourth National Institute of Health Functional Genomics of
      Critical Illness and Injury Symposium are described herein, in addition to
      deliverables for the field identified during panel discussions. Next steps for
      the community and suggestions for future research are presented.

PMID- 18828201
TI  - Comparison of community and referral intensive care unit patients in a tertiary
      medical center: evidence for referral bias in the critically ill.
AB  - OBJECTIVE: To determine the existence of referral bias in the critically ill by
      comparing the clinical and epidemiologic characteristics of community (Olmsted
      County, MN residents) and referral (non-Olmsted County residents) patients
      admitted to the intensive care unit. DESIGN: Retrospective, cohort study.
      SETTING: Academic tertiary care medical center. PATIENTS: Patients admitted to
      the medical and surgical intensive care units at Mayo Medical Center from 1995 to
      2004. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Residency status,
      demographics, Acute Physiology and Chronic Health Evaluation III score, intensive
      care unit admission diagnosis and treatment status, intensive care unit and
      hospital mortality, length of stay, and travel distances to Mayo Clinic. Referral
      patients with a medical intensive care unit admission were more severely ill, had
      greater mortality rates and length of stay and were more likely to receive an
      active intensive care unit intervention compared with community patients (p <
      0.0001). Referral and community patients who had a surgical intensive care unit
      admission had similar severity of illness, length of stay, and intensive care
      unit mortality rate. Hospital mortality rate was lower in the referral surgical
      patients compared with community surgical patients (p = 0.0001). When adjusted
      for severity of illness, intensity of treatment, and admission source, community
      and referral medical intensive care unit patients had a similar risk of hospital
      death, whereas referral surgical patients had a lower risk of hospital death
      compared with community patients. Referral patients who had a medical intensive
      care unit admission and traveled greater distances to Mayo Clinic had greater
      mortality rates and length of stay; those who had a surgical intensive care unit
      admission and traveled greater distances had lower mortalities and length of
      stay. CONCLUSIONS: Patients who resided outside of our local community and who
      had medical admissions to the intensive care unit were more severely ill, had
      greater mortality rates, and had longer length of stay compared with community
      patients. Our findings support the existence of referral bias in critically ill
      medical patients at our tertiary medical center.

PMID- 18828202
TI  - Proceedings of the 5th International Conference on Marine Pollution and
      Ecotoxicology. June 2007. Hong Kong. Special issue dedicated to Professor John
      Gray.

PMID- 18828203
TI  - Towards the elimination of rabies in Eurasia. Proceedings of a joint OIE/WHO/EU
      international conference. May 27-30, 2007. Paris, France.

PMID- 18828204
TI  - [Screening, risk assessment, questions in life insurance].

PMID- 18828205
TI  - Proceedings of the 10th International Symposium on Hyphenated Techniques in
      Chromatography and Hyphenated Chromatographic Analysers. January 30-February 1,
      2008. Bruges, Belgium.

PMID- 18828207
TI  - Living in a safe chemical world. Proceedings of the 10th International Congress
      of Toxicology. Tampere, Finland. July 11-15, 2004.

PMID- 18828206
TI  - From animals to man--50 years of development. Proceedings of the International
      Berlin Symposium on Bornavirus Infections. January 26-28, 2008. Berlin, Germany.

PMID- 18828208
TI  - Pneumolabyrinth after cochlear implantation in large vestibular aqueduct
      syndrome.

PMID- 18828209
TI  - [Cerebral damage due to hypoglycaemia in otherwise healthy breast-fed term
      infants].

PMID- 18828210
TI  - Proceedings of the 7th International Symposium on Polymer Therapeutics. Valencia,
      Spain.

PMID- 18828211
TI  - Obesity in America:  large portions, large proportions.

PMID- 18828212
TI  - Vitamin E and prostate cancer:  where do we stand?

PMID- 18828213
TI  - On call.  I found your November 2002 article on maximum heart rate very
      interesting.  But since I take Tenormin for high blood pressure, the new formula
      doesn't seem to apply to me.  How can I figure out my maximum rate?  I'm 48 years
      old, and I don't take any other drugs or have any other problems.

PMID- 18828214
TI  - Osteoarthritis: causes and diagnosis.

PMID- 18828215
TI  - Disorders of ejaculation.

PMID- 18828216
TI  - Work, vacations, and retirement: will they affect your health?

PMID- 18828217
TI  - On call.  I reread your articles on congestive heart failure when I was diagnosed
      with the condition last month.  My breathing is back to normal, and I feel well. 
      My doctor has prescribed all the medications you recommended, but he disagreed
      with one.  He said that since I'm taking Vasotec, I should stop my aspirin.  Do
      you agree?

PMID- 18828218
TI  - Life after 50: a new Harvard study of male sexuality.

PMID- 18828219
TI  - Osteoarthritis: symptoms and treatment.

PMID- 18828220
TI  - Zinc and prostate cancer.

PMID- 18828221
TI  - On call. Foot size and penile length.

PMID- 18828222
TI  - Air travel and your health.  Up, up, and away.

PMID- 18828223
TI  - Minding your mind: how to keep your brain young with proper care and feeding. 
      The challenges.

PMID- 18828224
TI  - Dolphins for the doldrums?

PMID- 18828225
TI  - On call. Vitamin a and macular degeneration.

PMID- 18828226
TI  - Compartmentalizing AIDS.

PMID- 18828227
TI  - A really big pain: acute epididymitis.

PMID- 18828228
TI  - High incidence of HIV in US blacks underscores need for national AIDS strategy.

PMID- 18828229
TI  - Senate repeals HIV travel ban.

PMID- 18828230
TI  - Images in HIV/AIDS. HIV-associated toxic megacolon.

PMID- 18828231
TI  - Pharmacokinetic interactions between ritonavir-boosted darunavir and NNRTIs: a
      report of 3 cases.
AB  - Pharmacokinetic interactions among antiretroviral agents may influence the
      potency or toxicity of coadministered drugs. Here we present 3 patients with
      extensive protease inhibitor and NRTI resistance for whom ritonavir-boosted
      darunavir (DRV/r) and an NNRTI were components of a successful antiretroviral
      regimen. These cases provide a context in which to review pharmacokinetic data
      pertaining to the coadministration of DRV/r and an antiretroviral agent from the
      NNRTI class. Although dose adjustments are not currently recommended when DRV/r
      is given in combination with any of the commonly prescribed NNRTIs, plasma levels
      of both darunavir and these NNRTIs are altered when they are used concomitantly.
      Understanding these pharmacokinetic changes might allow clinicians to predict
      which patients may be more vulnerable to adverse effects or inadequate antiviral
      activity caused by this drug interaction.

PMID- 18828232
TI  - Editorial comment: a plethora or options in multidrug-resistant HIV-1 infection.

PMID- 18828233
TI  - Challenge of coadministering antiretroviral therapy and oral anticoagulants in
      HIV-positive patients.
AB  - With an improved life expectancy, HIV-positive patients now face interactions
      between antiretroviral therapy and medications for chronic medical problems. One
      example is thromboembolism and its treatment with oral anticoagulants. To date,
      there have been 9 case reports documenting drug interactions between oral
      anticoagulants and antiretroviral agents. We conducted a retrospective case
      series to better understand the challenges of anticoagulation management in HIV
      positive patients receiving antiretroviral therapy. Of the 9 cases evaluated, the
      median percentage of international normalized ratio (INR) measurements of blood
      clotting time within the therapeutic range was 28.6%. Of those INRs outside the
      therapeutic range, 50.5% were subtherapeutic and 21.2% were supratherapeutic. A
      heightened awareness of the potential difficulty in achieving adequate
      anticoagulation in patients on antiretroviral regimens is warranted.

PMID- 18828234
TI  - HIV prevention and testing: update from the 17th International AIDS Conference.

PMID- 18828235
TI  - Bob Bowers: the pirate of Dane County. Poster contest combines art with awareness
      to deliver a message of hope.

PMID- 18828236
TI  - The next generation of human growth hormone. How Serostim and tesamorelin measure
      up.

PMID- 18828237
TI  - Point-of-care testing for measuring hemoglobin A1c: is it really worthwhile?

PMID- 18828238
TI  - Transfer of bodies to the University of Edinburgh after the 1832 anatomy act.

PMID- 18828239
TI  - The role of sport in the rehabilitation of patients with spinal injuries.

PMID- 18828240
TI  - Did the tenth-century viking Egil Skallagrimsson (c.AD 910-990) have Paget's
      disease?

PMID- 18828241
TI  - Human behavior and animal welfare.

PMID- 18828242
TI  - The accuracy of the Guardian RT continuous glucose monitor in children with type
      1 diabetes.
AB  - OBJECTIVE: The aim of this study was to determine the accuracy of the Guardian RT
      system (Medtronic Minimed, Northridge, CA) in young children and adolescents with
      type 1 diabetes (T1D) during different scenarios of glucose levels and sensor
      age. METHODS: At five clinical centers, 30 subjects between 4 and 17 years old
      with T1D were recruited. All subjects had a glycosylated hemoglobin level of
      <or=10.0% and were using an insulin pump. Subjects initially used a Guardian RT
      for approximately 1 week at home. Each subject was then hospitalized overnight
      for about 18 h in a clinical research center, during which time insulin-induced
      hypoglycemia occurred, along with frequently sampled glucose. RESULTS: There were
      1,511 laboratory glucose measurements paired with glucose measurements from 48
      Guardian RT sensors. Overall, the median absolute difference (AD) was 21 mg/dL,
      and the median relative AD (RAD) was 14%, with 64% of sensor values meeting
      International Organization for Standardization home glucose meter criteria. The
      median AD was 27 mg/dL for reference glucose values<or=60 mg/dL and 25 mg/dL for
      reference glucose values<or=70 mg/dL. The median RAD was 19% for reference
      glucose values 71-120 mg/dL, 14% for reference glucose values 121-180 mg/dL, and
      10% for reference glucose values>180 mg/dL. CONCLUSIONS: The Guardian RT appears
      to perform as well in children with T1D as it has been reported to perform in
      adults with diabetes. The Guardian RT has an accuracy similar to that of other
      available continuous glucose monitors and can give important and useful clinical
      information.

PMID- 18828244
TI  - National rural hospital charges due to ambulatory care sensitive conditions.
AB  - In this policy brief, we estimate and document the national magnitude of charges
      associated with hospitalizations due to ambulatory care sensitive conditions
      (ACSCs) in rural hospitals. The brief also reports this type of charge by
      hospital size. This research will inform policy makers about the magnitude of
      rural preventable hospitalizations and the associated potential savings in
      hospital resource utilization.

PMID- 18828243
TI  - JDRF randomized clinical trial to assess the efficacy of real-time continuous
      glucose monitoring in the management of type 1 diabetes: research design and
      methods.
AB  - BACKGROUND: While real-time (RT) continuous glucose monitoring (CGM) systems may
      revolutionize treatment of type 1 diabetes (T1D), there is insufficient evidence
      currently available to support widespread utilization of these devices. The
      Juvenile Diabetes Research Foundation (JDRF) CGM Study Group developed a
      randomized clinical trial to determine if RT-CGM can improve glycemic control and
      quality of life in children and adults with T1D. This paper presents the research
      design and methods that are being employed in this study. METHODS: The JDRF CGM
      Study Group trial is a randomized, parallel group, efficacy and safety study.
      Subjects with T1DM who meet eligibility criteria are randomized to either
      standard self-monitoring of blood glucose (SMBG) alone or use of any of the three
      current RT-CGM systems as a supplement to SMBG. After the 6-month randomized
      period, the Control Group is offered use of RT-CGM, and both groups are studied
      for an additional 6 months. Subjects are divided into two cohorts: the Main Study
      Cohort includes subjects with baseline glycosylated hemoglobin (HbA1c) 7.0-10.0%
      inclusive, and the Exploratory Pilot Study Cohort includes subjects with
      HbA1c<7.0%. Difference in HbA1c is the primary outcome in the Main Study. Other
      outcomes include the percentage of sensor glucose values within the 70-180 mg/dL
      range, scores on questionnaires that assess the impact of RT-CGM on living with
      T1D, and the cost-effectiveness of RT-CGM. RESULTS: Recruitment for the study was
      completed on December 15, 2007. CONCLUSION: Results of this clinical trial should
      help establish whether or not current RT-CGM devices are beneficial to patients
      with T1D.

PMID- 18828245
TI  - Regional variation in rural hospital charges due to ambulatory care sensitive
      conditions.
AB  - In this policy brief, we estimate and document the regional magnitudes of charges
      associated with hospitalizations due to ambulatory care sensitive conditions
      (ACSCs) in rural hospitals. This research will inform policy makers about the
      regional magnitudes of rural preventable hospitalizations and the associated
      potential savings in hospital resource utilization when rural patients receive
      timely and effective primary care.

PMID- 18828246
TI  - Reliance on independently owned pharmacies in rural America.
AB  - The purpose of this policy brief is to provide researchers, policy makers, and
      stakeholders with the locations of independently owned pharmacies in rural
      America that are the sole sources of access to local pharmaceutical services.
      Organizations representing those pharmacies have argued that the advent of
      Medicare prescription drug plans threatens the financial viability of those
      pharmacies (Grisnik 2006). In addition, some pharmacists have expressed concerns
      about changes in Medicaid reimbursement for pharmaceuticals brought about by the
      Deficit Reduction Act (DRA) of 2005. We focus on those communities with only one
      pharmacy, independently owned, to lay a foundation for analyzing vulnerability of
      pharmacy services in rural America.

PMID- 18828248
TI  - The "most honest and most devoted of women": an early modern defense of the
      professional actress.

PMID- 18828249
TI  - Recent developments in health insurance, life insurance, and disability insurance
      case law.
AB  - This survey reviews significant state and federal court decisions from 2006 and
      2007 involving health, life, and disability insurance. Also reviewed is a June
      2008 Supreme Court decision in the disability insurance realm, affirming that a
      conflict of interest exists when an ERISA plan sponsor or insurer fulfills the
      dual role of determining plan benefits and paying those benefits but noting that
      the conflict is merely one factor in considering the legality of benefit denials.
      In addition, this years' survey includes compelling decisions in the life and
      health arena, including cases addressing statutory penalties and mandated
      benefits, as well as some ERISA decisions of note. This year, the Texas Supreme
      Court held that Texas's most recent version of the prompt payment statute
      abolished the common law interpleader exception and allowed the prevailing
      adverse claimant in an interpleader action filed beyond the sixty-day statutory
      period to recover statutory interest and attorney fees from the insurer.
      Meanwhile, the Court of Appeals of New York upheld the constitutionality of a
      statute mandating coverage for contraceptives in those employer-sponsored health
      plans that offer prescription drug coverage, including those plans sponsored by
      faith-based social service organizations. In the ERISA context, litigants
      continue to fight over the standard of review with varying results. In a unique
      assault on the arbitrary and capricious standard of review, the Fourth Circuit
      found that an ERISA plan abused its discretion when it failed to apply the
      doctrine of contra proferentem to construe ambiguous plan terms against itself.
      In more hopeful news for plan insurers, the Tenth Circuit held that claimants are
      not entitled to review and rebut medical opinions generated during the
      administrative appeal of a claim denial before a final decision is reached unless
      such reports contain new factual information.

PMID- 18828250
TI  - Making the most of episodic antiviral therapy for genital herpes.

PMID- 18828251
TI  - Assessing female sexual dysfunction in epidemiological studies: why is it
      necessary to measure both low sexual function and sexually-related distress?

PMID- 18828252
TI  - Here's to the health of the CEO.

PMID- 18828253
TI  - Look closely at processes to prevent these hospital-acquired infections.

PMID- 18828255
TI  - Are you getting patients involved in their care?

PMID- 18828254
TI  - You'll need this data on patient QI involvement.

PMID- 18828256
TI  - Joint Commission focuses on pediatric drug errors.

PMID- 18828257
TI  - Use proven strategies for error disclosure to patients.

PMID- 18828258
TI  - The Practitioner 1868-2008: supporting GPs for 140 years.

PMID- 18828259
TI  - On inhalation in diseases of the throat. 1868.

PMID- 18828260
TI  - Exercise can be effective therapy for depression.

PMID- 18828261
TI  - GPs should be vigilant for eating disorders.

PMID- 18828262
TI  - Updated asthma guideline will improve outcomes.

PMID- 18828263
TI  - Vascular problems.

PMID- 18828264
TI  - GPs are losing their core roles.

PMID- 18828265
TI  - Limited hepatic resection by laparoscopy-assisted mini-laparotomy for the
      treatment of hepatocellular carcinoma in cirrhotic patients.
AB  - Surgical resection is standard treatment for hepatocellular carcinoma but is
      often not possible in the presence of cirrhosis or poor liver function. We
      present a method of performing limited hepatectomy in patients with
      hepatocellular carcinoma and cirrhosis. We call this method laparoscopy-assisted
      mini-laparotomy (LAML). The site of the tumor is localized by ultrasound through
      a laparoscope, and a small skin incision is made over that site to facilitate
      removal of the portion of liver containing the tumor. Eleven patients underwent
      limited hepatic resection by LAML. The tumors were on the margin of the liver.
      There was no hospital mortality or serious complications. The average length of
      hospital stay was 6.4 days. LAML can be safely performed for hepatocellular
      carcinoma in cirrhotic patients. It decreases operating time, length of hospital
      stay, and blood loss.

PMID- 18828266
TI  - Predictors of type II neurologic complications after coronary artery bypass graft
      surgery.
AB  - The study objective was to determine predictors, and adverse outcomes of
      postoperative type II neurologic complications. An 11-year cohort (N=12,706)
      study with 595 coronary artery bypass graft (CABG) patients with a neurologic
      complication, and 7793 patients without any neurologic complications was
      conducted. This study examined 26 potential risk factors and 13 outcome
      variables. Logistic regression analysis found that patients were more likely to
      experience a neurologic complication after CABG if they were older than 70 years
      of age [odds ratio (OR), 3.8; 95% confidence interval (CI), 3.1-4.5; P < 0.001],
      had a previous intervention within 10 days before surgery (OR, 3.4; 95% CI, 1.4
      8.3; P = 0.008), or had a higher creatinine level (OR, 0.9; 95% CI, 0.95-0.99; P
      = 0.013). Additionally, there was a significant difference between CABG patients
      with and without neurologic complications on 12 outcome variables. Type II
      neurologic complications after CABG are common and associated with an increased
      risk of postoperative morbidity and mortality.

PMID- 18828267
TI  - Safety in healthcare is not a new concept.

PMID- 18828268
TI  - Coexisting congenital diaphragmatic hernia, esophageal atresia, and
      tracheoesophageal fistula: a case report and review of the literature.
AB  - Esophageal atresia (EA) with or without tracheoesophageal fistula (TEF) and
      congenital diaphragmatic hernia (CDH) are two relatively common neonatal
      conditions. The coexistence of the two conditions in the same newborn is
      extremely rare. This is a case report of a newborn with CDH and concurrent EA and
      TEF. Aspects of diagnosis and the literature on the subject are also reviewed.

PMID- 18828269
TI  - Apoptosis and adenocarcinoma of the cardia: expression of p53, Bcl-2, Bcl-XL,
      WAF1, and fas proteins and association with characteristics of the tumors.
AB  - Our knowledge regarding the biology of the gastroesophageal junction
      adenocarcinomas is still incomplete. Paraffin-embedded sections from 31
      surgically resected primary cardia adenocarcinomas were examined by
      immunohistochemistry. Statistical analysis showed that Bcl-2 expression was
      significantly correlated with the age of the patients (P = 0.043), whereas Bcl
      X(L) expression was inversely correlated with Bcl-2 expression (P = 0.021). An
      inverse correlation of high statistical significance was also found between p53
      and Bcl-2 expression (P = 0.000). Fas expression was highly correlated with tumor
      stage (P = 0.006), degree of differentiation (P = 0.044), and the stage of the
      disease (P = 0.029). A significant correlation was also observed between the
      expression levels of WAF1 and Fas (P = 0.037), Fas and Bcl-X(L) (P = 0.018), and
      WAF1 and p53 (P = 0.018). These proteins may contribute to the estimation of the
      properties of adenocarcinomas of the gastroesophageal junction, facilitating
      prognosis of cancer patients treated by multimode therapy.

PMID- 18828270
TI  - Surgical management for stenosis of the pancreaticojejunostomy.
AB  - The management of the stenosis of the pancreaticojejunostomy is dictated by the
      state of the anastomosis and the residual pancreas, endocrine, and exocrine
      pancreatic function. We report a case of a 23-year-old woman who presented with
      recurrent attacks of acute pancreatitis. Four years ago, she was diagnosed with
      pancreatic injury with a transection of the body of the pancreas. A computed
      tomography scan showed a pancreatic laceration, and she underwent a Letton-Wilson
      surgical procedure. At present, we think that the stenosis of the anastomosis of
      the pancreaticojejunostomy caused the recurrent attacks of acute pancreatitis. We
      performed a reoperation for stenosis of the pancreaticojejunostomy by the
      previous surgical procedure. Reoperation is a useful and radical procedure to
      relieve recurrent acute pancreatitis caused by the stenosis of the
      pancreaticojejunostomy.

PMID- 18828271
TI  - Emergency surgery for acute respiratory failure secondary to spontaneous thyroid
      hemorrhage.
AB  - A 42-year-old woman was evaluated for an emergency at our surgical department for
      acute dyspnea associated with a spontaneous and rapidly enlarging mass of the
      neck. Clinical examination revealed a large, firm, nonfluctuant thyroid swelling
      on the right side of the neck. An urgent computerized tomography scan showed a
      hematoma within the right lobe of the thyroid and tracheal deviation with marked
      luminal narrowing. Because of the rapid progression of respiratory distress,
      endotracheal intubation by flexible laryngoscopy revealing normal vocal cords
      function and emergency total thyroidectomy were performed. During the operation,
      the thyroid gland showed a huge, edematous, nonfluctuant, rubbery, firm swelling
      with easy bleeding on touch, but the capsule appeared to be intact without
      rupture. Microscopic examination revealed a colloid multinodular goiter with
      massive parenchymal hemorrhage. Recovery was uneventful, and the patient was
      discharged 2 days after the operation.

PMID- 18828272
TI  - Prognostic value of the PAI-1 4G/5G polymorphism in invasive ductal carcinoma of
      the breast.
AB  - The study group was derived from the archive materials of 55 invasive ductal
      breast cancer (IDC) patients who had undergone breast-preserving surgery (partial
      mastectomy/ axillary dissection). All patients included in the study had
      clinically T(1)-2, N0-M0 invasive ductal carcinoma. Genomic DNA species were
      extracted from paraffin-embedded blocks, and plasminogen activator inhibitor type
      1 (PAI-1) gene 4G/5G genotyping was done by polymerase chain reaction (PCR)
      restriction fragment length polymorphism (RFLP). Patient demographics, axillary
      metastasis status, metastatic lymph nodi/total dissected lymph nodes from axilla,
      histopathologic characteristics of tumors, local recurrences, and survival ratio
      were assessed. PAI-1 4G/5G genotype frequencies were 4G/4G (64%), 4G/5G (31%),
      and 5G/5G (5%) in the patient group. According to the results based on
      frequencies, the demographics were not different. Five-year local recurrence rate
      of 4G/5G patients was the lowest (2/17, 12%) (P = 0.02). Also five-year distant
      metastases ratio of 4G/5G patients was the highest (18%) (P = 0.01). Five- and 10
      year disease-free survival rates for the 4G/4G, 4G/5G, and 5G/5G groups were 97%
      and 94%, 82% and 77%, and 100% and 94%, respectively (P = 0.004). The results of
      this study indicate that the 4G allele in the PAI 1 gene had a negative impact on
      local recurrence and disease-free survival of patients with clinical T(1)-2N0M0
      IDC.

PMID- 18828273
TI  - How much skill should we need for a VATS lobectomy in stage I lung cancer? An
      evaluation of surgeon groups.
AB  - Although there has been progress in video-assisted thoracic surgery (VATS), there
      have been no reports about the skill needed to perform this surgery for patients
      with stage I lung cancer. We reviewed a randomized series of surgeons in a single
      institution and attempted to identify the quality of skill needed in this
      surgery. Cases of surgery on clinical stage I non-small cell lung cancer (NSCLC)
      involving 103 patients (56 VATS and 47 conventional approach) from January 2000
      to April 2006 were assessed for eligibility. We reviewed these patients and
      placed them in random order into three surgeon groups (groups A, B, and C) that
      were based on surgeons who had performed 50 lobectomies through thoracotomy.
      Three patients were converted to a thoracotomy. Of the remaining 53 patients, 17
      were in group A, 15 were in group B, and 21 were in group C. There were no
      significant differences between the three surgeon groups regarding technical
      factors such as blood loss and operation time. After a short initial learning
      period, two of the three surgeon groups significantly decreased total blood loss.
      Morbidity and recurrence did not differ between the groups, and there was no
      mortality in our sample. The volume of VATS operations performed by individual
      surgeons who have had good training in open lobectomy may not make for a positive
      impact on clinical outcomes. The decision for a VATS lobectomy in cases of stage
      I NSCLC should not be limited only by a surgeon's thoracoscopic experience.

PMID- 18828274
TI  - Immunohistochemical expression of pl30cas in papillary thyroid carcinoma.
AB  - pl30cas is a multifunctional protein that is involved in many aspects of cellular
      physiology, including adhesion, migration, and regulation of the cell cycle, and
      can be regulated by a variety of stimuli. We immunnohistochemically examined
      pl30cas, cytokeratin 19 (CK19), and epithelial membrane antigen (EMA) expression
      in 37 cases of papillary thyroid carcinoma (PTC), 11 cases of Hashimato's
      thyroiditis with papillary carcinoma-like changes, and 17 cases of nodular
      hyperplasia. All PTCs were immunoreactive for pl30cas. We showed no positivity in
      normal thyroid follicles adjacent to the tumor. However, we observed focal
      positivity in thyroid follicles in association with heavily lymphoplasmacytic
      infiltrate or degeneration away from the tumor in 19% of PTCs and in 18% (3/17)
      of nodular hyperplasias. This is the first study of expression of pl30cas; these
      finding suggest that pl30cas may have a role in tumorigenesis and its expression
      may contribute to the diagnosis of papillary carcinoma.

PMID- 18828275
TI  - Differentiated carcinoma of the thyroid: a paradigm shift in surgical approach.
AB  - Thyroid cancer commonly present with a thyroid nodule, a few with cervical
      lymphadenopathy or metastases. Total of 1320 patients with differentiated thyroid
      cancer (DTC) managed in Surgical department, Government General Hospital,
      Chennai, India for a period of 11 years (1990-2001) were analyzed and 600
      patients followed up for a mean of 5.5 years (range, 1-11 years). Aim was to
      discuss the advantage of ultrasound guided fine needle aspiration cytology (FNAC)
      in increasing the preoperative pick up of DTC, Papillary microcarcinoma,
      advantages of total thyroidectomy as the initial operation for DTC and management
      of thyroid remnant by completion thyroidectomy or radioiodine I 131 ablation.
      McNemer's test used for estimating efficacy of ultra sound guided (USG) FNAC,
      Kaplan-meier survival analysis to calculate mortality and Cox's proportional
      hazards regression analysis for disease free survival were used in the study.

PMID- 18828276
TI  - Protecting protected areas.

PMID- 18828277
TI  - Do parks work? Impact of protected areas on land cover clearing.
AB  - This paper evaluates the impact of protected areas on land-cover clearing, using
      a metadata analysis of information on 49 locations from 22 countries. Protected
      areas had significantly lower rates of clearing in comparison to their
      surroundings. In addition, protected areas had also significantly lowered rates
      of clearing within their boundary following initiation of protection. Thus,
      protected areas do appear to be effective at limiting overall land-cover
      clearing. There was some variation in the rates of clearing across regions, where
      most protected areas from North America and Europe showed positive rates of land
      cover change, while protected areas from Asia had the highest rates of land-cover
      clearing. While most protected areas from North America and Europe involved a
      relatively smaller number of actors, a greater number of actors and drivers of
      clearing was implicated in protected areas from Asia, Africa, and Latin America,
      indicating the increased difficulties faced by park management in these regions.
      In contrast, country income levels and the International Union for the
      Conservation of Nature and Natural Resources category of protection did not
      appear to impact the likelihood of land-cover clearing in protected areas.

PMID- 18828278
TI  - Interpretation reduces ecological impacts of visitors to world heritage site.
AB  - Minimal-impact interpretation is widely used to reduce the ecological impacts of
      visitors to protected areas. We tested whether verbal appeals and/or role-model
      demonstrations of minimal-impact behavior by a trained guide reduced noise,
      litter, and trampling impacts on hiking trails in a subtropical rainforest.
      Interpretation did reduce impacts significantly. Different interpretive
      techniques were more effective for different impacts. The experimental groups
      were mature, well-educated professionals; interpretation may differ in
      effectiveness for different visitors. Interpretation by skilled guides can indeed
      reduce visitor impacts in protected areas, especially if role modeling is
      combined with verbal appeals.

PMID- 18828279
TI  - Historical decline in coral reef growth after the Panama Canal.
AB  - The Panama Canal is near its vessel size and tonnage handling capacity, and
      Panamanians have decided to expand it. The expansion of the Canal may consider
      the historical long-lasting impacts on marine coastal habitats particularly on
      sensitive coral reefs. These potential impacts were discussed during the national
      referendum as were other equally important issues, such as its effects on
      forests, watersheds, and water supply. Coral growth rates provide a direct
      measure of coral fitness and past environmental conditions comparable to analyses
      of tree rings. We examined stable isotopes, metal geochemical tracers, and growth
      rates on a century-long (1880-1989) chronology based on 77 cores of the dominant
      reef-building coral Siderastrea siderea collected near the Caribbean entrance to
      the canal. Our results showed a gradual decline in coral growth unrelated to
      changes in sea surface temperature but linked to runoff and sedimentation to
      coastal areas resulting from the construction and operation of the Panama Canal.

PMID- 18828280
TI  - Considering the functional value of common marine species as a conservation
      stake: the case of sandmason worm Lanice conchilega (Pallas 1766) (Annelida,
      Polychaeta) beds.
AB  - Conservation of the marine environment mainly focuses on threatened elements and
      more precisely on vulnerable and endangered species like birds and mammals. When
      dealing with the conservation of marine habitats, the scientific community is
      mainly interested in hot spots of diversity, like seagrass beds in Europe, or hot
      spots of endemism, like coral reefs in tropical areas. Nevertheless, using the
      example of a common and widespread marine invertebrate, the sandmason worm
      (Lanice conchilega, Polychaeta, Terebellidae), we show that vulnerability and
      rarity are not the only criteria to take into account in order to select the best
      natural element for conservation. This species can form dense beds that increase
      biodiversity, are attractive feeding grounds for birds and fishes, and have a
      high socioeconomic value. In consequence, they have a high functional value that
      should be considered as an important conservation stake. Through the example of
      the Chausey archipelago and the Bay of the Mont Saint-Michel (France), we propose
      a synthetic interdisciplinary approach to evaluate the conservation needs of
      these beds. The issue is even more pressing when one considers that these natural
      elements and many similar ones still do not benefit from any legal protection in
      Europe despite their high heritage value.

PMID- 18828281
TI  - Pup production and breeding distribution of the Caspian seal (Phoca caspica) in
      relation to human impacts.
AB  - Aerial surveys of Caspian seals on the winter ice field in Kazakhstan territorial
      waters were carried out in February 2005 and 2006 to assess the annual pup
      production for the species and natural predation on newborn pups. Estimated pup
      production was 21063 in 2005 and 16905 in 2006 (including an estimated figure for
      pups born in Russian territory in each year). The breeding population size of
      approximately 20 000 females is much less than published estimates from the late
      1980s. Eagles were the principal natural predators of pups. Commercial icebreaker
      routes passed through areas of dense pup concentrations in 2006, although not in
      2005. Our findings have important implications for the development of
      conservation strategies for the species. Natural mortality, loss to predators,
      and, more important, the current hunting quota substantially exceed the
      recruitment of the Caspian seal population. Anthropogenic sources of mortality
      should be managed to avoid further declines in the species.

PMID- 18828282
TI  - Historical marine ecology: examining the role of fisheries in changes in North
      Sea benthos.
AB  - The organisms living on and in the sea floor, the benthos, represent an important
      ecological group. Although some (shellfish) have an economic value, most do not,
      and so little long-term data are available. We have identified three sources of
      historic benthic data for the North Sea, a regional sea that has been subjected
      to multiple human impacts for at least several hundred years. Each dataset has
      its limitations, but by their use together some issues emerge. Wider community
      shifts were observed in the shorter term and a number of extirpations at the
      scale of the North Sea were seen over longer time scales. The extirpated taxa
      share a number of characteristics consistent with an effect of fisheries such as
      fragile morphology. We must concentrate now on furthering our understanding of
      the ecological significance of shifts in dominance of particular functional units
      and protecting those habitats and species most vulnerable to fisheries-driven
      extirpation.

PMID- 18828283
TI  - Beyond the desertification narrative: a framework for agricultural drought in
      semi-arid East Africa.
AB  - In the 20th century, much research was done on desertification. Desertification
      developed into a complex and vague construct that means land degradation under
      specific conditions. Projects focusing on land degradation in semiarid East
      Africa have met with limited success because farmers prioritize drought as the
      major productivity-reducing problem. Yet studies on long-term rainfall trends
      have not confirmed that droughts are more frequent. In this article, we combine
      drought and land degradation effects into an Agricultural Drought Framework,
      which departs from the farmers' prioritization of drought and accommodates
      scientists' concern for land degradation. It includes meteorological drought,
      soil water drought, and soil nutrient drought. The framework increases insight
      into how different land degradation processes influence the vulnerability of land
      and farmers to drought. A focus on increased rainwater use efficiency will
      address both problems of land degradation and drought, thereby improving
      productivity and food security in semiarid East Africa.

PMID- 18828284
TI  - Spatial configuration of land-use/land-cover in the Pujal-Coy project area,
      Huasteca Potosina region, Mexico.
AB  - This article analyzes the relationship between the configuration and spatial
      reorganization of land-use and land-cover in the Pujal-Coy project area, Huasteca
      Potosina region, eastern San Luis Potosi, Mexico, as well as the relationship
      between these changes and the environmental conditions prevailing in the area.
      Land-use and land-cover changes were determined through the analysis and
      interpretation of satellite images from different dates. The changes identified
      in the different study periods were correlated with the prevailing physical
      factors. The results show that the spatial configuration of farming activities,
      initially induced by the implementation of a regional development project, is
      highly correlated to the presence of limiting factors such as soil type, slope,
      and climate. Particularly, the former represents the element that has led to the
      establishment of the current distribution pattern of farming activities.

PMID- 18828285
TI  - Rocky desertification, antidesertification, and sustainable development in the
      karst mountain region of Southwest China.

PMID- 18828286
TI  - Add nurses to exemption list.

PMID- 18828287
TI  - RCN relaunches nursing department in bid to boost professional support.

PMID- 18828288
TI  - Cultural shift.
AB  - A scheme to encourage nursing recruits from a minority ethnic group that
      traditionally does not view nursing as a positive career has achieved success in
      an inner city area of London.

PMID- 18828289
TI  - A spoonful of training...
AB  - A nurse has developed an e-learning package to help hospital staff administer
      medicines safely.

PMID- 18828290
TI  - Learning from each other.
AB  - The National Institute for Health and Clinical Excellence (NICE) shared learning
      awards are open to everyone who submits information about implementing NICE
      guidance to its database.

PMID- 18828291
TI  - Rights of passage.

PMID- 18828292
TI  - Assessing the effect of fibromyalgia on patients' sexual activity.
AB  - AIMS: The primary aim of this study was to investigate whether a questionnaire
      developed for patients with rheumatoid arthritis (RA) could also be used with
      patients who have fibromyalgia. A secondary aim was to assess the impact of
      fibromyalgia on sexuality. METHOD: In the first of two phases the face and
      content validity of a sexuality questionnaire already being used in patients with
      RA were assessed in a qualitative, audio-taped, interview study of five patients
      with fibromyalgia. The second phase consisted of a self-report questionnaire
      distributed to 60 patients with fibromyalgia. FINDINGS: The interview data
      confirmed that the content of the RA sexuality questionnaire was relevant to
      patients with fibromyalgia. A total of 43 (72%) questionnaires were returned and,
      of these, 41 (95%) were usable. Patients reported that fibromyalgia had altered
      their sexual relationship. They cited pain, stiffness, fatigue, reduced sexual
      drive and the impact of drug therapy as the main reasons. CONCLUSION: The
      symptoms associated with fibromyalgia had a negative effect on sexual enjoyment.
      The questionnaire appears to be useful in addressing sexuality in patients with
      fibromyalgia.

PMID- 18828293
TI  - Essential elements in developing evidence-based practice.
AB  - This article addresses the principles of evidence-based practice and considers
      the essential elements involved in the process. The overall aim of the article is
      to equip nurses with the necessary knowledge and skills to use evidence-based
      practice competently and to make a positive contribution to patient outcomes.

PMID- 18828294
TI  - Fractures: pathophysiology, treatment and nursing care.
AB  - Many nurses working in the primary and secondary sectors will care for patients
      who have sustained fractures. The ability to assess these patients systemically
      in addition to the injury is important in detecting complications and enhancing
      bone healing at the various stages of injury or treatment. This article describes
      different types of fracture and principles for their management. The nursing care
      of patients who has sustained a fracture is discussed from admission to
      discharge.

PMID- 18828295
TI  - Syphilis.

PMID- 18828296
TI  - Mind your mentoring.

PMID- 18828297
TI  - Teaching a good death.

PMID- 18828298
TI  - Crossing continents.

PMID- 18828299
TI  - [In verietate concordia].

PMID- 18828300
TI  - [Foreign internship in geriatric nursing education in the Netherlands: providing
      mobility within the scope of education].

PMID- 18828301
TI  - [Claims and reality of health promotion in nursing: European public health
      graduate education].

PMID- 18828302
TI  - [Colleagues in geriatric nursing learn to improve their communication: the
      multicultural team as challenge and chance].

PMID- 18828303
TI  - [Requirements in food hygiene in inpatient facilities: "expanding the housewife
      horizon"].

PMID- 18828304
TI  - [Alternative ambulatory care concepts--3: Integrated group home for seniors with
      mental disabilities: new perspectives for a new target group].

PMID- 18828305
TI  - [Nursing continuing education exemplified by nephrology specialty continuing
      education: a possible future model].

PMID- 18828306
TI  - [Self organized learning in nursing education: innovation in the education
      system].

PMID- 18828307
TI  - [Prophylaxis in nursing education--1: Health promotion nursing reduces nursing
      dependence].

PMID- 18828308
TI  - [Implementing adequate general practice instruction: clinical curriculum is
      established].

PMID- 18828309
TI  - [Insufficient funding of nursing service in paediatrics. The case of the DRG
      E77C].
AB  - For most of the existing German Diagnosis Related Groups (G-DRG) the German
      generalised compensation system for medical services in hospitals does not
      distinguish between children and adults. There is a risk of the cost of high
      maintenance paediatric patients not being covered. This problem is tried to be
      solved by implementing a split based on the patient's age. Thus children under
      the age of one year will be classified to a different DRG than older patients
      with the same diagnosis. A study of working time combined with an analysis of the
      so-called "Pflegepersonalregelung-Minuten" carried out by the Ernst-Moritz-Arndt
      University of Greifswald exemplarily shows the different intenseness of care
      between paediatric and adult patients. Furthermore, the different intenseness of
      care correlates with the labour cost of the university hospital and shows the
      extensions of the shortfall for the most profitable DRG based on guidelines of
      the "Institut fur das Entgeltsystem im Krankenhaus" (Institute for the
      compensation system in hospitals, InEK). Last but not least it discusses if the
      age-splitting planned for the 2008 DRG-Catalogue might improve the financial
      situation. Moreover the authors point out possibilities for a proper compensation
      for paediatrics in the G-DRG system.

PMID- 18828310
TI  - [Legal regulations for part time employment: right and responsibilities in
      triangle relationship].

PMID- 18828311
TI  - [Importance of nurse counseling: new hot beverage or cold coffee?].

PMID- 18828312
TI  - [From case to case: compensating for nutrition-induced deficiencies].

PMID- 18828313
TI  - [Recognizing and understanding illnesses: nausea and vomiting as primary
      symptoms].

PMID- 18828314
TI  - Field hypotension in patients who arrive at the hospital normotensive: a marker
      of severe injury or crying wolf?
AB  - INTRODUCTION: Trauma patients with hypotension in the field who arrive at a
      hospital with a normal blood pressure (BP) may not be recognized as significantly
      injured. METHODS: Over a 5-year period, demographic, injury severity, and
      disposition data were retrospectively analyzed for patients > or =16 years of age
      with documented hypotension in the field (systolic BP < or =90 mm Hg) and normal
      BP (systolic BP >90 mmHg) on hospital arrival (hypotensive group). This group was
      compared to patients with normal BP in the field and on hospital arrival
      (normotensive group). RESULTS: During the study, 2207 patients with documented BP
      were transported directly from the scene. Of this number 44 (2%) were assigned to
      the hypotensive group, 2086 (94%) were assigned to the normotensive group, and 77
      (4%) patients were hypotensive on hospital arrival. The hypotensive group had a
      systolic BP in the field of 70 +/- 26 mmHg compared to 140 +/- 26 mmHg in the
      normotensive group (p < 0.0001). Arrival BP at the hospital was normal in both
      groups. Compared to the normotensive group, the hypotensive group had higher
      Injury Severity Scores (22.0 vs. 11.1, p < 0.0001), lower Glasgow Coma Scores
      (10.8 vs. 14.0, p < 0.0001), lower Revised Trauma Scores (65 vs. 7.4, p <
      0.0O01), more emergency department deaths (7% vs. 0%, p < 0.001), longer lengths
      of stay in the intensive care unit (8.6 vs. 7.0 days, p < 0.0001) and hospital
      (14.0 vs. 7.0 days, p < 0.0001), and increased hospital mortality (18% vs. 4%, p
      < 0.001). LIMITATIONS: The retrospective design and exclusion of patients without
      documentation of BP in the field may have resulted in selection bias. CONCLUSION:
      Despite these limitations, field hypotension is a marker of significant injury in
      patients arriving at the hospital normotensive.

PMID- 18828315
TI  - Availability of tobacco cessation services in free clinics.
AB  - BACKGROUND: This study sought to determine the availability of tobacco cessation
      services in free clinics. METHODS: In fall 2007, a survey was e-mailed to free
      clinics that asked respondents to indicate the availability of13 different
      services recommended as part of the Treating Tobacco Use and Dependence
      guidelines set by the United States Public Health Service (USPHS). Seventy-two
      percent (n=51) of clinics responded to the survey. RESULTS: The majority of
      clinics enforce a "no tobacco use" policy inside the clinic (98%), encourage
      health care providers to advise patients to quit (90%), ask patients about
      tobacco use behavior on intake (78%), provide self-help materials (70%), and
      offer pharmacotherapy (e.g., bupropion) for quitting (60%). Fewer clinics offer
      fee nicotine replacement therapy (35%), display counter-advertisements in waiting
      areas and patient rooms (35%), have a designated staff person or volunteer to
      help patients quit (26%), evaluate whether health care providers offer tobacco
      cessation advice (30%), or have onsite tobacco cessation classes (22%). One out
      of 3 free clinics offer comprehensive (at least 9 of 13) tobacco cessation
      services using the USPHS Treating Tobacco Use and Dependence guidelines.
      LIMITATIONS: Small sample size limits analytical techniques that can be applied,
      as well as interpretation of results. CONCLUSION: Free clinics offer an excellent
      opportunity to reach the uninsured population for tobacco cessation. Although 1
      in 3 clinics is comprehensive in its approach to reduce tobacco use among their
      patients, many have yet to undertake the breadth of clinic-based strategies that
      can promote quitting. This study serves as an opportunity and a challenge to free
      clinics to expand their service delivery into the area of behavioral health.

PMID- 18828316
TI  - Towards a more comprehensive understanding of cancer burden in North Carolina:
      priorities for intervention.
AB  - OBJECTIVE: To apply 4 measures of population burden in examining cancer burden in
      North Carolina and to identify priorities for intervention. METHODS: Four
      measures were used: incidence, mortality, prevalence, and years of potential life
      lost (YPLL). The North Carolina Central Cancer Registry provided summary data on
      incidence and mortality and record-level data that were examined using SEER*Stat
      software to calculate prevalence. North Carolina vital statistics (mortality)
      data and life expectancy estimates stratified by age, race, and sex were used to
      calculate YPLL. Each cancer site was ranked according to burden for each of the 4
      individual burden measures and summarized into an overall rank. Burden was
      examined overall and by sex and race. PRINCIPAL FINDINGS: Four cancers-
      lung/bronchus, female breast, prostate, and colon/rectum--accounted for
      approximately 57% of the total cancer incidence, prevalence, mortality, and YPLL
      in North Carolina. Patterns of burden in gender and race subgroups were similar,
      although non-whites often had higher mortality rates than did whites despite
      similar incidence rates. An estimated 207,583 people were living with cancer in
      2004 Breast and prostate cancer accounted for 42% of these survivors.
      Lung/bronchus cancer was the most severe cancer, accounting for more deaths and
      years of life lost than any other 5 cancers combined. CONCLUSIONS: Each of the 4
      measures provides unique insight and guidance for cancer coordination and control
      efforts. Lung/bronchus, female breast, prostate, and colon/rectum cancers
      accounted for the majority of North Carolina's cancer burden and should be
      priorities for intervention.

PMID- 18828317
TI  - Policy forum: Cancer in North Carolina.

PMID- 18828318
TI  - Addressing the burden of cancer for the people of North Carolina.

PMID- 18828319
TI  - A cancer policy agenda for North Carolina.

PMID- 18828320
TI  - The North Carolina Cancer Plan: a living plan for the people of North Carolina.

PMID- 18828321
TI  - Cancer resources in North Carolina.

PMID- 18828322
TI  - Research for North Carolina: The University Cancer Research Fund.
AB  - In 2008 an estimated 40,000 North Carolinians will be diagnosed with cancer. This
      disease is the number one cause of death in our state and will claim more than
      17,000 lives this year. North Carolina is swimming against a demographic tide of
      growth and aging that will bring 80,000 new cancer cases by 2050, despite
      continued improvements in cancer prevention, early detection, and treatment. By
      establishing the University Cancer Research Fund, North Carolina has taken a
      bold, nation-leading step forward toward improving the future health and well
      being of its citizens. Research that creates new knowledge, turns that knowledge
      into advances in treatment, screening, and prevention, and then ensures delivery
      of those advances across the state-that research is the key that unlocks the
      doors to a new and better future. The Fund will make that research possible. As
      has often been the case, North Carolina was ahead of the national curve by
      creating the UCRF in July 2007. In November 2007, Texas passed a $3 billion bond
      referendum to provide $300 million annually to support cancer research over the
      next decade. In 2005, California passed a $3 billion bond referendum to support
      stem cell research. Perhaps noting the downturn in federal funding for biomedical
      research, other states are watching these states' investments to see if they
      improve their citizens' health and make researchers nationally competitive. We
      will rigorously evaluate the UCRF to show the nation that North Carolina has
      taken a bold and wise step. The North Carolina General Assembly and the people of
      North Carolina have presented the University of North Carolina at Chapel Hill,
      the UNC Lineberger Comprehensive Cancer Center, the North Carolina Cancer
      Hospital, and UNC Health Care with an astounding opportunity and responsibility.
      We embrace that opportunity and that responsibility and pledge ourselves to our
      shared vision of a better future for the citizens of North Carolina.

PMID- 18828323
TI  - The Commission on Cancer: Opportunities for North Carolina cancer care.

PMID- 18828324
TI  - Cancer clinical trials in North Carolina.

PMID- 18828325
TI  - The cancer registry profession: a unique role in cancer care and control.

PMID- 18828326
TI  - Dentistry and the prevention, diagnosis, and treatment of oral cancer in North
      Carolina.

PMID- 18828327
TI  - The North Carolina Cancer Assistance Unit: a resource for low-income, uninsured
      patients with cancer.

PMID- 18828328
TI  - Cancer survivorship.

PMID- 18828329
TI  - Cancer incidence and mortality trends in North Carolina.

PMID- 18828330
TI  - Using Master Settlement Agreement dollars to fund a statewide tobacco cessation
      quitline.

PMID- 18828331
TI  - Promoting cancer prevention through beauty salons and barbershops.

PMID- 18828332
TI  - Advocacy in action.

PMID- 18828333
TI  - Medicare GPCIs, the GEM coalition, and KMA.

PMID- 18828334
TI  - Fatal iatrogenic hyperphosphatemia.
AB  - Hypertonic sodium phosphate enemas are available for relief of constipation. They
      are widely used as colorectal laxatives because of their efficacy and because
      most patients tolerate the preparation well. Nevertheless, their use has been
      associated with decreases in intravascular volume as well as measurable changes
      in serum phosphorus and calcium levels. Usually these effects are transient and
      cause no ill effects. Severe toxicity may occur when the osmotically active
      hypertonic phosphate enema is retained or when it is administered to a patient
      with a decreased glomerular filtration rate. We report an elderly patient with
      previously normal renal function who developed severe hyperphosphatemia,
      hypocalcemia, and cardiac arrest after the administration of hypertonic sodium
      phosphate enemas for the treatment of an ileus. We review the patient
      characteristics that increase the risk of adverse effects from hypertonic sodium
      phosphate enemas and emphasize the danger that moderate dehydration poses when
      considering the use of these cathartics.

PMID- 18828335
TI  - Evaluation of consequences of implementation of police crisis intervention team
      in Louisville.
AB  - The police crisis intervention team (CIT) for managing emergent situations that
      involve mentally ill subjects was instituted in Louisville in 2002. The program
      was described in a special article that appeared in the Journal of the Kentucky
      Medical Association in June 2003. To determine the impact of CIT on the outcome
      of police calls, we reviewed police records for 2002, the first full year of CIT
      operation, and 2004, the year after consolidation of city and county police
      forces, and compared them with pre-CIT statistics (2001), when available. We also
      reviewed local jail occupancy records after the introduction of CIT and compared
      them to pre-CIT records. Louisville Metro Police average some 2672 CIT runs
      annually. The majority of these runs (90%) result in bringing a subject to the
      hospital. Arrest rate for CIT runs is lower than non-CIT runs (2.1% vs 6.2%,
      respectively, P < 0.01). Hostage negotiation team callouts dropped by half. While
      the occupancy of the mental health unit in Jefferson County Jail has stayed
      relatively constant at around 1,100 patients/year, the referrals to intense
      psychiatric services (eg, Central State Hospital) has greatly dropped (from 53%
      in 2001 to 26.8% in 2004, P < 0.01). The data suggests that the introduction of
      CIT has had an overall positive effect on outcomes of situations in which
      mentally ill subjects are confronted by police officers.

PMID- 18828336
TI  - Care for the elderly patient.

PMID- 18828337
TI  - Protecting health from climate change--a challenging task.

PMID- 18828338
TI  - Tobacco smoking and pulmonary tuberculosis: a case-control study.
AB  - A case-control study was carried out to assess if the tobacco smoking is
      associated with development of active pulmonary tuberculosis in 153 cases with
      active pulmonary tuberculosis and 160 control subjects. Detailed information on
      smoking habits was collected from cases and controls using questionnaire. It was
      seen that tobacco smoking was associated with pulmonary tuberculosis. The
      estimated crude odd's ratio (OR) of the association was 1.66 (95% confidence
      interval: 1.01-2.73) . The age adjusted OR was 1.70 (95% CI: 1.01-2.88), p <
      0.05. The increased risk for pulmonary tuberculosis was significant in men who
      had smoked for over 20 years (OR 3.07; 95% CI: 1.37-6.86). The adjusted OR for
      heavy smokers (more than 20 bidis per day) was 2.72 (95% CI: 1.19-6.20). There
      was a dose-response relationship between the number of bidis smoked daily and the
      risk of development of pulmonary tuberculosis. The study showed that tobacco
      smoking is associated with pulmonary tuberculosis, with a dose-response
      relationship with the number of bidis consumed daily.

PMID- 18828339
TI  - Allergies in India: an analysis of 3389 patients attending an allergy clinic in
      Mumbai, India.
AB  - A total of 3389 consecutive patients attending the allergy clinic over a period
      of 5 years (2003-2007) were analysed by the same physician. Males outnumbered
      females ie, 53.05% versus 46.95%.; 89.17% of the patients were adults and 10.83%
      were children. More than 80% of the patients were young, below 40 years of age.
      Nasobronchial allergies viz, asthma, rhinitis or asthma with rhinitis formed the
      largest group of patients (76.9%). Total serum IgE levels were elevated in every
      patient (except in those with contact dermatitis). The highest levels of IgE were
      seen in patients with atopic dermatitis (mean 1615.47 IU/ml). The house dust
      mite, D farinae, showed the highest incidence (77.13%) of positive reactions.
      Positive reactions to foods (16.48%) were more than that reported in western
      countries, whereas positive reactions to pollen were comparatively low (8.61%).
      In the contact dermatitis group, nickel sulphate (38.5%) and Parthenium
      hysterophorus (36.5%) were the commonest allergens on patch testing. Penicillins,
      sulphonamides and non-steroidal anti-inflammatory drugs were the drugs most
      commonly found to cause allergic reactions in India. The incidence of atopy is
      estimated to be 28.96% in a randomised survey of the Indian population.

PMID- 18828340
TI  - Endo-DCR: is it an end of the road for external DCR?
AB  - Endo-DCR is a safe, quick, less traumatic, with minimal blood loss and post
      operative discomfort and last but not the least, avoids external scar. It has
      high success rate in both primary and secondary cases. Fifty two cases of chronic
      dacryocystitis were treated by the endoscopic technique including 33 females and
      19 males in mean age group 35.8 year, 29 left eye and 23 right eye with 8
      patients cannulated with nasolacrimal tube with very good results and few
      complications.

PMID- 18828341
TI  - Role of hysterectomy and its alternatives in benign uterine diseases.
AB  - There is a rising trend of hysterectomy rate as too frequently it is being
      performed now for conditions like symptomatic fibroids and dysfunctional uterine
      bleeding which can be treated alternatively. Hysterectomy, as with all other
      major surgeries, is also associated with increased mortality and morbidity risks.
      Various medical and surgical lines of management, other than hysterectomy, are
      presently accessible for the above conditions. Availability of safer and newer
      treatment options is great boon for women with changing attitudes towards child
      bearing and uterine conservation.

PMID- 18828342
TI  - A comparative study between total contact casting and conventional dressings in
      the non-surgical management of diabetic plantar foot ulcers.
AB  - Of all non-traumatic amputations 50% occur in Diabetics, mostly as a final
      outcome of foot ulcers. A major biomechanical factor in the causation of foot
      ulcers in persons with diabetes mellitus is elevated peak plantar pressure.
      Offloading the ulcer area in the form of equalisation of pressure across the
      plantar surface can accelerate healing of the ulcer. Total contact casting is one
      such method of offloading, and this study attempts to investigate the advantages
      of the above method as compared to conventional dressings in the physiatric
      management of the depth--ischaemia grades 1A, 1B, 2A, 2B neuropathic plantar
      ulcers in a diabetic patient. The outcome measure was the time taken for complete
      resolution of the ulcers. Of the 29 patients in Category A treated with total
      contact casting involving a total of 39 foot ulcers, 36 healed, which was
      statistically significant (p < 0.05) as compared to 25 out of the 33 ulcers
      healing in Category B consisting of 26 patients treated by conventional dressings
      alone. Total contact casting is an effective, rapid, economical, ambulatory and
      outpatient--based method for the treatment of diabetic foot ulcers.

PMID- 18828343
TI  - Prevalence of hypothyroidism and importance of cholesterol estimation in patients
      suffering from major depressive disorder.
AB  - The coexistence of hypothroidism and depression is already reported and both of
      these conditions are known to share some common clinical symptoms. Serum
      cholesterol level is known to be altered in either condition considered
      separately. But, no report is obtained regarding serum cholesterol level when
      both the conditions coexist. In this study, 78 patients (61 females and 17 males,
      age ranged 19 to 67 years) suffering from major depressive disorder were
      included. Serum T3, T4, TSH and cholesterol levels were estimated in all of them.
      Sixty-two patients were found to be euthyroid and 16 patients (11 females, 5
      males) were found to be hypothyroid. Among female patients, 6 had subclinical
      hypothyroidism and 5 had overt hypothyroidism. Among male patients 3 had
      subclinical hypothyroidism and 2 had overt hypothyroidism. The overall prevalence
      of hypothyroidism in major depressive disorder was estimated as 20.5%. Mean serum
      cholesterol level in 62 euthyroid patients was found to be 150.9% +/- 16 mg% and
      that of 16 hypothyroid patients to be 190.7 +/- 12 mg% showing a significant
      difference (p < 0.01). Thus estimation of cholesterol in major depressive
      disorder patients may give an idea regarding their thyroid status and vice-versa.

PMID- 18828344
TI  - Transthoracic cutting needle biopsy: a valuable diagnostic procedure.
AB  - Intrathoracic mass lesions, especially peripherally situated masses, often
      present as a problem as tissue diagnosis is not always possible by
      cytopathological examination. Cutting needle biopsy may be the method of choice
      in selected cases for tissue diagnosis. Cutting needle biopsy is indicated for
      patients with peripherally situated mass lesions abutting chest wall, which are
      non-vascular and non-cystic in nature.

PMID- 18828345
TI  - Psychogenic excoriation responding to fluoxetine: a case report.
AB  - Compulsive skin picking, 'acne excoriee', neurotic (psychogenic) excoriation,
      dermatotillomania, occurring in 2% dermatology patients mostly in women, is a
      result of excessive scratching, picking, gouging or squeezing of the skin using
      teeth, tweezers, nail files, pins and knives, etc. The lesions are usually found
      on face and also on upper limbs and upper back, areas patients can easily reach.
      They may occur in absence or in response to skin pathology or sensation of
      itching. A young female patient attended OPD with the complaints of multiple
      excoriated lesions over the face, arms and forearms. The diagnosis was
      psychogenic excoriation which is an uncommon psychodermatological condition. She
      was treated with fluoxetine and behaviour therapy. The patient recovered fully
      with above treatment at the end of 3 months. Psychogenic excoriation is an
      uncommon psychodermatological condition which responds well to selective
      serotonin reuptake inhibitors and behaviour therapy (habit reversal training).

PMID- 18828346
TI  - Pregnancy associated breast cancer--the obstetrician's role.
AB  - Breast cancer is the most common cancer in many geographic areas, the most
      frequent cause of cancer deaths in women, and is also the cancer most likely to
      be seen during pregnancy and lactation. Delay in diagnosis appears to be the
      primary reason for the generally worse prognosis overall for all patients with
      breast cancer diagnosed during pregnancy and lactation. In this context, the
      patient's family physician or obstetrician who performs the routine antenatal
      examinations can play an important role by performing a vital breast examination
      which might bring to light and prompt timely investigation of otherwise
      asymptomatic breast masses.

PMID- 18828347
TI  - Longitudinal vaginal septum 'obstructive variety'--a challenge for gynaecologist.
AB  - The cases which have been presented here have varied presentations but all the
      three patients in the series had acyclical abdominal pain. Since the uterus is
      functional there is collection of blood in the pouch formed due to the vaginal
      septum. This is a potential site for infection and could result in foul smelling
      discharge. Failure of fusion of lower ends of mullerian ducts that form vagina
      results in longitudinal vaginal septum. The septum may be partial or complete.
      The clinical syndrome of double uterus with vaginal obstruction (unilateral,
      partial or complete) and ipsilateral renal agenesis (same as of the side of
      obstruction) is rare. This combination is suggestive of embryologic arrest
      occuring at 8 weeks of pregnancy that simultaneausly affected the mullerian and
      metanephric ducts.

PMID- 18828348
TI  - Skeletal muscle metastasis in a case of bronchogenic carcinoma.

PMID- 18828349
TI  - S-metoprolol: the 2008 clinical review.
AB  - Metoprolol is a widely used cardioselective beta-blocker. However, like all other
      beta-blockers it is also a racemic mixture of R- and S- isomers. The beta 1
      blocking activity (cardioselectivity) of metoprolol resides in S-isomer while R
      isomer exhibits beta 2 blocking activity. As both these isomers have different
      pharmacological properties, racemic metoprolol can be considered a combination of
      two different drugs in a fixed 1:1 ratio. The needless administration of the non
      beta-blocking R-enantiomer that makes up 50% of racemate actually puts the
      patient at an increased risk of side-effects, drug interactions and loss of
      cardioselectivity with up-titration of dosing. Clinical experience with chirally
      pure S-metoprolol at half the dose of racemate has shown it to be as effective as
      racemate in the treatment of patients with hypertension and angina. S-metoprolol
      has been shown to be effective and well-tolerated in patients with coexisting
      diabetes, COPD, and hyperlipidaemia. This confirms higher cardioselectivity of S
      metoprolol in clinical settings. Less interaction potential of S-metoprolol
      compared to R-isomer further makes it a sensible choice in patients taking CYP2D6
      inhibitors or in patients with heart failure or hepatic insufficiency. This
      article reviews differing properties of two isomers of metoprolol with focus on
      clinical experience with S-metoprolol.

PMID- 18828350
TI  - Rabeprazole plus domperidone: the answer for gastro-oesophageal reflux disease.
AB  - To study and document the efficacy and tolerability of rabeprazole and
      domperidone in the treatment of patients suffering from gastro-oesophageal reflux
      disease (GERD), an open, prospective, non-comparative study was carried out among
      50 adult patients of either sex attending gastroenterology OPD of a leading,
      tertiary-care teaching hospital in Mumbai with the clinical diagnosis of GERD.
      One capsule of rabeprazole and domperidone was swallowed in empty stomach each
      day for up to 4 weeks by the patients. Rabeprazole and domperidone provided
      significant and remarkable improvement in symptoms of GERD. Although, the
      improvement was observed at first follow-up visit (within 2 weeks), continuing
      treatment for 4 weeks provided additional gains. Almost all patients tolerated
      the drug well. Most patients (94%) had excellent or good relief as assessed by
      their physician whilst 86% of patients rated treatment with rabeprazole and
      domperidone as good or excellent. Rabeprazole and domperidone not only provided
      desired relief of symptoms of GERD but also is very well tolerated. This
      combination may also improve the quality of life of patients suffering from GERD.

PMID- 18828351
TI  - [Geographical distribution of DDTs, PCBs and phthalate esters in coastal surface
      sediments of Yellow Sea].
AB  - Using the data of the second survey of marine pollution baseline, the
      geographical distribution and constitution were investigated, and preliminarily
      evaluated the ecological risk based on the corresponding sediment quality
      guidelines. The results showed that, the sites with high concentrations of PAEs
      over the corresponding guidelines were mainly located in the Dalian Bay (1 389.8
      ng/g) and surrounding sea areas of Lvshun (1 928.0 ng/g), and the main components
      of PAEs were DBP and DEHP. Only at the outlet of Dalian Bay, the concentration of
      PCBs (24.2 ng/g) was slightly higher than the ERL guideline level (22.7 ng/g),
      while the sites with concentrations exceeding the ERL guideline (1.58 ng/g) were
      mostly situated in the coastal areas of Dalian Bay (6.3-7.6 ng/g), Yantai-Weihai
      (4.5-10.3 ng/g), Jiaozhou Bay (5.5-21.2 ng/g) and Haizhou Bay (27.4-62.9 ng/g),
      and the content at one site was even above the ERM guideline (46.1 ng/g). The
      compositions of DDT indicated that, the main metabolites of p, p'-DDT was p, p'
      DDD, and there may be new inputs of DDT in the coastal areas of Dalian Bay,
      Weihai, Jiaozhou Bay and Haizhou Bay, as well as the outer sea area of Shandong
      Peninsula, where the possible sources were technical dicofol and/or technical
      DDT. The surface sediments in these sea areas had certain ecological risk,
      especially at one individual site in the Haizhou Bay with much higher ecological
      risk.

PMID- 18828352
TI  - [Geochemical cycling of mercury in the sediment of Hongfeng Reservior].
AB  - Spatial and temporal distributions of total and methyl mercury and controlling
      factors were investigated based on cold vapor atomic fluorescence detection.
      Total mercury levels in the whole sediments are (0.392 +/- 0.070) microg/g,
      without significant variations between different seasons, but generally increase
      toward the sediment-water interface. Total mercury levels are higher compared to
      data reported in other uncontaminated reservoirs and Wujiangdu Reservoir. This
      indicates there are mercury contaminations in Hongfeng Reservoir. Methyl mercury
      concentrations are highest in spring, without significant variations in other
      seasons. The peak values of methyl mercury typically appear in the upper 8 cm of
      the sediment profiles which are also the zones of sulfate-reducing bacteria
      activities. The seasonal variation and maximum peak value distributions of methyl
      mercury in sediment are mainly controlled by seasonally migration of oxic/anoxic
      boundary layer. Total mercury concentrations in the pore water and partition
      coefficients for THg in solid phase and water phase are mainly controlled by
      temperature or redox potential. Total mercury concentrations in the pore water
      have no relationship with total mercury concentrations in solid phase. However,
      the methyl mercury concentrations in the pore water have a strong relationship
      with those in solid phase (r = 0.70, p < 0.001). The methyl mercury
      concentrations in solid phase and pore water are controlled by solid/water
      partition coefficient, as well as methyl mercury production.

PMID- 18828353
TI  - [Distributions of dissolved inorganic mercury in the lower part of the Three
      Gorges Reservoir].
AB  - One year after the first filling stage of the Three Gorges Reservoir(TGR),
      dissolved inorganic mercury (Hg(DI)) was measured in August 2004. Concentration
      of Hg(DI) varied from undetection to 82.6 ng x L(-1) with average of 22.7 ng x L(
      1). Stratification of Hg(DI) in the TGR was obviously. Concentrations of Hg(DI)
      were much higher in the layers above 20 m than in deep waters. Concentration of
      Hg(DI) in the Xiangxi River varied from undetection to 61.4 ng x L(-1) with
      average of 18.0 ng x L(-1). The Hg(DI) concentration increased obviously after
      the filling of the TGR. Large amount of Hg was retented with the deposition of
      sediment in the TGR. The retention of Hg by the TGR needs the further research.

PMID- 18828354
TI  - [Seasonal variations of HCOOH and HCHO in precipitation in Guiyang].
AB  - Formic acid and formaldehyde are the important and ubiquitous chemical
      constituents in the atmosphere. Precipitation in Guiyang, the capital city of
      Guizhou province, was analyzed with ICS-90 ion chromatography for their
      concentration changes in a year. The volume mean weight average concentration
      (VMWA) is (13.27 +/- 25.92) micromol/L and (7.89 +/- 8.92) micromol/L for formic
      acid and formaldehyde, respectively. Both species demonstrated higher
      concentration during winter-half-year than the summer-half-year. Day-time
      concentration is higher than the night-time, the diurnal variations for both
      chemical constituents indicate the sources from human activities and
      photochemical reactions. Regression analysis of concentration vs precipitation
      volume and deposition amount vs precipitation volume reveals that dilution and
      scavenging of precipitation in the below-cloud process are responsible for the
      changes of the concentrations. The significant correlation between formic acid
      and formaldehyde suggests similar sources or reaction relationship. The known
      aqueous oxidation of formaldehyde, however, can not be used to explain the link
      of the two compounds, and thus should not be the major source of formic acid in
      Guiyang, Instead, photochemical reactions of unsaturated hydrocarbons (natural or
      anthropological) were the major sources for formic acid and formaldehyde.

PMID- 18828355
TI  - [Nitrogen concentration and nitrogen isotope in epilithic mosses for indicating
      the spatial variation and sources of atmospheric nitrogen deposition at Guiyang
      area].
AB  - Tissue N concentration and delta15 N signature in epilithic mosses were
      investigated along 4 directions from urban area to rural area at Guiyang city.
      Mosses N concentration ranged from 0.85% to 2.97% and showed significant decrease
      from urban area (2.24% +/- 0.32%) to suburb (1.27% +/- 0.13%), reflecting the
      level of atmospheric N deposition decreased away from urban. While slightly
      higher tissue N re-emerged at rural area beyond 25km (mean = 1.33%-1.75%),
      suggesting increased N deposition occurred in the rural area. Mosses delta15 N
      values varied from - 12.50 per thousand to - 1.39 per thousand characterized with
      getting less negative from urban to rural area. More negative delta15 N
      signatures of urban mosses (mean= - 8.87 per thousand(-) - 8.59 per thousand)
      mainly indicated the extensive NH3 sources released from excretory wastes and
      sewage, while mosses growing at farther suburb or rural area had less depleted
      delta15 N values (mean = - 3.83 per thousand(-) - 2.48 per thousand), indicating
      the large sources of agricultural NH3 emission connected with fertilizer
      application. Moreover, the pattern of mosses delta15 N variation in this study
      was opposite to areas where N deposition was dominated by oxidized form N (NO(x))
      with generally positive mosses delta15 N. Accordingly, we concluded that reduced
      NH, was the dominant N form in atmospheric deposition at Guiyang area, which
      would be of great value for understanding the spatial variation and sources of
      atmospheric N deposition.

PMID- 18828356
TI  - [Distribution characteristic and correlation relationship of reactive sulfur and
      heavy metals in sediments of Meiliang Bay and Wuli Lake of Taihu Lake].
AB  - The distribution characteristic of acid volatile sulfide (AVS), simultaneously
      extracted metals (SEM), and total metals were studied in the surface and core
      sediments of Meiliang Bay and Wuli Lake in Taihu Lake. It was found that there
      were similar distribution characteristics for AVS and SEM in surface sediments,
      and the concentration of AVS and SEM decreased from the steady deposition area of
      estuary to the centre of the bay (lake). The ratio of AVS/SEM was < 1 in the
      surface sediments, indicating that heavy metals in surface sediment might have
      potential bioavailability. The concentration of AVS increased with sediment
      depth, followed by decrease with large variation, while the concentration of SEM
      remained constant. Though comparing the concentration of SEM with total metals,
      it was shown that the extracted Cu and Ni decreased with sediment depth,
      indicating that increasing association of Cu and Ni with sulphides in deeper
      sediment layer, while the lower extracted ratios for Pb and Zn compared with
      sulfidic sediment illustrated that the AVS should not have a strong controlling
      on sediment Pb and Zn. From the molar ratio of AVS and reactive iron, it is known
      that the heavy metals were rather dynamic and active in sediments of studied
      sites.

PMID- 18828357
TI  - [Heavy metals in environmental media around drinking water conservation area of
      Shanghai].
AB  - The levels of heavy metals in Shanghai drinking water conservation area were
      determined, and the spatial distributions and main sources of heavy metals were
      investigated. Moreover, the ecological risk assessment of heavy metals was
      conducted. Some conclusions can be drawn as follows: (1) The average
      concentrations of Cd, Hg, Pb, Cu, Zn, Ni, Cr and As in road dust were 0.80, 0.23,
      148.45, 127.52, 380.57, 63.17, 250.38 and 10.37 mg x kg(-1) respectively. In
      terms of the pollution level, the values of soils were relatively lower, with the
      mean contents of 0.16 (Cd), 0.33 (Hg), 30.14 (Pb), 30.66 (Cu), 103.79 (Zn), 24.04
      (Ni), 65.75 (Cr) and 6.31 mg x kg(-1) (As) severally; meanwhile the average
      levels of heavy metals in vegetables were 0.010 (Cd), 0.016 (Hg), 0.36 (Pb),
      12.80 (Cu), 61.69 (Zn), 2.04 (Ni), 2.41 (Cr) and 0.039 mg x kg(-1) (As)
      respectively. (2) Semivariogram and multivariate analysis indicated that heavy
      metals pollution of soils was induced by anthropogenic activities mostly, and the
      pollutants produced by traffic were the major source of heavy metals in road
      dust. (3) The order for heavy metal enrichment coefficients of vegetables was as
      following: Zn (0.589) > Cu (0.412) > 0.102 (Ni) > Cd (0.059) > Cr (0.061) > Hg
      (0.056) > Pb (0.012) > As (0.007), and the results indicated that Cd and Zn in
      vegetables were mainly from the soils, and the other metals were probably from
      the pollutants in the atmosphere. (4) Sediments in drinking water conservation
      area were probably derived from soils around; however, there was no significant
      relationship between heavy metals contents of them. (5) The results of ecological
      risk assessment of heavy metals showed that heavy metals in soils were in no
      warning to warning situation, and warning to light-warning situation for road
      dust and vegetables. The fuzzy synthesis judgment for all the environmental media
      around drinking water conservation area was warning to light-warning.

PMID- 18828358
TI  - [Contamination characteristics and pollutant sources analysis on PAHs in shallow
      groundwater in suburb of Taihu plain].
AB  - To investigate shallow groundwater quality in Taihu plain, south of Jiangsu
      province, 56 samples were collected in north area (C area), north east area (W
      area) and east area (S area). The concentrations of priority 16 polycyclic
      aromatic hydrocarbons (PAHs) were analyzed by HP 6890-GC. Hierarchical cluster
      analysis (HCA) and Molecular ratios were used to characterize their possible
      pollution sources. Concentrations of total priority 16 PAHs in shallow
      groundwater samples ranged from below method detection limits (< MDLs) to 32.45
      microg/L with the average value of 4.42 microg/L, which were predominated by
      three and four-ring PAHs. High contents of PAHs were found in the vicinity of
      industrial areas. Ratios of specific PAH compounds including
      phenanthrene/anthracene (Phe/Ant), fluoranthene/pyrene (FL/Pyr), chrysene/
      benzo(a)/anthracene (Chr/BaA), low-molecular-weight PAH/high-molecular-weight PAH
      (LPAH/HPAH) were calculated to evaluate the possible sources of PAH
      contamination. These ratios reflected a mixed pattern of pyrolytic and petrogenic
      inputs of PAHs with different proportion in shallow groundwater. Hierarchical
      cluster analysis (HCA) results showed that the abnormal benzo (k) fluoranthene
      concentration dominated the HCA results in C area, the abnormal
      benzo(a)anthracene concentration dominated the HCA results in W area, and the
      abnormal benzo (b) fluoranthene concertration dominated the HCA results in S
      area. At level 0.05, FL, AcPy, Acp, Phe and Bap in C area had Pearson correlation
      between 0.680 and 0.712. BP, BaA and Bap in W area had Pearson correlation
      between 0.724 and 0.773. AcPy and Flu in S area had Pearson correlation 0.659,
      which meant that these PAHs listed in each areas might came from the same kind of
      sources.

PMID- 18828359
TI  - [Adsorbed non-point source pollution load of Jialing River basin].
AB  - Based on the American Universal Soil Loss Equation, focused on the two main
      factors that are hydrology condition and land management practice which can
      influence the soil loss in the watershed change yearly, and took into account the
      sediment transport process which can effect the soil loss differ spatially, a new
      sediment load evaluation method was put forward which can reflect the yearly
      change process of soil loss. Took Jialing River basin as a research example and
      validated the new evaluation method. Furthermore, according to the correlation
      between the sediment load and adsorbed nitrogen and phosphorus pollution load,
      established a yearly load evaluation model of the adsorbed nitrogen and
      phosphorus pollution. By virtue of the geographical information technology, the
      yearly load and spatial distribution of the adsorbed nitrogen and phosphorus
      pollution due to soil erosion in the Jialing River basin from 1990 to 2005 have
      been studied by the established model. The results show that adsorbed phase of
      nitrogen and phosphorus pollution are quite seriously in the subbasin of Bailong
      River and Xihanshui River. In recent years, adsorbed nitrogen and phosphorus
      pollution loads have declined year by year because of the conservation practices
      of soil and water in this basin. The average loads of adsorbed nitrogen and
      phosphorus pollution are 34 423 t/a and 1 848 t/a respectively in the past five
      years, which have reduced by about 60% from 1990.

PMID- 18828360
TI  - [Mobilization and transformation of phosphorus from water-soil interface of
      flooded soil].
AB  - Mobilization and transformation of phosphorus from water-soil interface of
      flooded agricultural soils is a concern, and it has been a leading cause of
      eutrophication of lakes and rivers. Using PVC soil trough, we modeled the
      mobilization and transformation of P, ferrous iron, ferric iron, dissolved
      organic carbon (DOC) between soil floodwater and porewater induced by flooding,
      and characterized the main factors that contributed to phosphorus release by
      using the principal component-partial least squares method. This study shows that
      flooding soils induced significant release of phosphate to the floodwater over a
      54-d period. Cumulative phosphate content in floodwater was 16 times as much as
      in porewater. The changes that occurred among the inorganic P forms during
      flooding were also invested. Significant changes in the inorganic P fractions Fe
      P, Al-P, Ca-P, and O-P occurred in soil during flooding. Typically, the Ca-P
      fraction was almost unchanged during flooding. The others decreased, and Fe-P
      contents during flooding decreased by 30.4%-72% of its initial value, which
      significantly contributed to the release of phosphate to floodwater and
      porewater. The major factors that affected the floodwater phosphate release were
      Eh, ferrous iron, ferric iron, and dissolved organic carbon (DOC). The factor
      that affected the porewater phosphate release was DOC. The predominant mechanism
      of DOC induced floodwater P release was ligand-enhanced dissolution, and that
      induced porewater P release was competitive sorption. Furthermore, ferric iron in
      porewater affected the porewater P release.

PMID- 18828361
TI  - [Formation mechanism of bioavailable phosphorus in sediments under the conditions
      of sediment re-suspension].
AB  - The concentrations of different sedimentary phosphorus forms and bioavailable
      phosphorus were studied and the formation mechanism of BAP in sediments was
      discussed, under the conditions of sediments re-suspension. The results show that
      sediment re-suspension had obvious effect on the distribution of different
      sedimentary phosphorus forms. The BD-P, Al-P, Ca-P were increased evidently and
      the NH4Cl-P was decreased with the time of sediment re-suspension extending. The
      BAP in sediments after re-suspended was reduced by 6.59%, indicating that
      sediment re-suspension could promote the transformation from BAP to
      nonbioavailable phosphorus. The formation of AAP might mainly have close
      relationships with BD-P. After extracting AAP, the BD-P was decreased by 33.4%
      averagely in the sediments after re-suspended, while the release of BD-P in
      sediments from the control experiment was increased by 19.8%, showing that the
      formation of AAP was affected marked by the properties of BD-P. The Olsen-P could
      be mainly formed from BD-P, Al-P, NaOH-nrP. The formation of Olsen-P was closely
      correlated to BD-P, based on the release of BD-P, Al-P, NaOH-nrP.

PMID- 18828362
TI  - [Vertical distribution of species of nitrogen and phosphorus in the sediments of
      Donghu Lake].
AB  - Donghu Lake is a typical urban shallow lake. Miaohu Lake was analyzed in
      Southwest of Donghu Lake. Characteristics of nitrogen and phosphorus in sediment
      cores were analyzed and assessed with investigation and chemical analysis in
      laboratory in 2004. Vertical distributions and seasonal changes of nitrogen and
      phosphorus chemical species in the sediments of two sampling sites were examined
      and analyzed. The results showed that concentration of TN decreased with the
      increase of sediment depth and the concentration of the mean TN was 1.62-3.17
      g/kg. The concentration of TN reached its minimum in spring, and began to
      increase in summer. The concentration of TN reached its maximum till autumn and
      winter. Dissolved ammoniac nitrogen (DAN) was controlled by both the content of
      TN and the sediment environment, so the vertical profiles and seasonal changes of
      DAN presented the same trend as those of TN. The lowest concentration of DAN was
      117.66 mg/kg in spring, and the highest concentration of DAN was 216.20 mg/kg in
      summer and autumn. It was decreasing in winter. Vertical profiles of phosphorus
      species showed that total phosphorus (TN), labile phosphorus (LP), Al- and Fe-
      bound phosphorus (Al-P, Fe-P) were characterized by a similar distribution
      pattern and enrichment in the upper 0-10cm sediment layers. The concentration
      decreased steeply within 10cm sediment layers, then it became steady. The
      concentration of TP, LP, Fe-P and Al-P was 0.255-3.36 g/kg, 0.192-11.00 mg/kg,
      13.47-1 379.94 mg/kg and 7.77-317.64 mg/kg, respectively. The results indicate
      that sources of pollution which cause water body in the lake eutrophication have
      the extraneous source and the internal one. After the extraneous sources are
      truncated, nutrient salt in sediments still possibly causes the lake to be at the
      eutrophication condition. Phosphorus is the most restricting nutritious element
      in Donghu Lake. The proportion of Fe-P is the biggest in spring and its
      proportion is 44.30%. These show that pollution is serious in Miaohu Lake.

PMID- 18828363
TI  - [Behavior of evolution and growth of dominant algae in the Chongqing urban
      section along the Three-Gorges valley].
AB  - Through sampling and analyzing algae species in natural water-body of the Yangtze
      river and the Jialing river located at Chongqing urban section along the Three
      Gorges valley, and combining with monitoring on the influencing parameters to
      algae growth, such as TN/TP, light intensities and current velocities by
      experimental simulation, the effect on the algae propagation behavior has been
      studied systemically. The results show that under static hydrological condition
      with various TN/TP and light intensities the Chlorophyta and Cyanophyta would
      grow rapidly while the Bacillariophyta disappear quickly, and other algae species
      had little change, and the total algal cell density could exceed 10(7) cells/L.
      However, even if under lower current velocity as about 0.03 m/s, the total algae
      cell density would increase at most obviously while its density could only reach
      10(6) cells/L, and the proportion of Bacillariophyta would increase with the
      increase of current velocity, the proportion of Chlorophyta and Cyanophyta begin
      decrease at same time. Apparently, evolution of the dominant algae species would
      take place according to the change of hydrological condition. The density of
      total algae is primal regressed to TN/TP and current velocities with coefficients
      of determination (R2) are all over 0.93 while it has lower regression coefficient
      with the light intensities. The samples analysis of the above two rivers under
      natural state also demonstrates that total algae density in the Jialing river is
      higher than that in the Yangtze river, and the Bacillariophyta has the absolute
      domination, and then are Cyanophyta and Chlorophyta, which fit in with the
      experimental results in our laboratory.

PMID- 18828364
TI  - [Physiological effects of metsulfuron-methy on Elodea nuttallii].
AB  - Physiological effects of metsulfuron-methy on Elodea nuttallii was studied. The
      growth status, the photosynthetic pigments content and activities of anti
      oxidation enzymes of Elodea nuttallii were examined with different contents of
      metsulfuron-methyl in cultural solution. The results showed that metsulfuron
      methy could stimulate the sprout bourgeoning but restrained the growth of frond
      remarkably. At lower concentrations, metsulfuron-methy could increase the content
      of chlorophyll at the beginning, but inhibited the syntheses of chlorophyll
      ultimately and reduced the plant's photosynthetic capacity. Activities of CAT and
      POD increased at first and then decreased, while SOD activities increased all the
      time. With higher concentration and longer treatment time, the activities of anti
      oxidation enzymes would decrease. It is indicated that metsulfuron-methy can
      arise the formation and accumulation of reactive oxygen species in Elodea
      nuttalii, and induce activities of anti-oxidation enzymes. When stress intensity
      exceeds a certain value, the activities of anti-oxidation enzymes will be
      inhibited and reactive oxygen species can not be removed in time and will finally
      result in oxidative damages to the plant. This may be an important toxicity
      mechanism of this kind of herbicide to aquatic plants.

PMID- 18828365
TI  - [Role of irradiance on the seasonality of Skeletonema costatum Cleve blooms in
      the coastal area in East China Sea].
AB  - With field culture experiments and model calculations, the role of light on why
      in both spring and summer Skeletonema costatum Cleve blooms can occur in the
      coastal area in East China Sea were studied. The results show that the growth
      optimal light intensity (I(opt)) of S. costatum increases gradually to a maximum
      of 121.6 W x m(-2) with temperature (t) up to 25 degrees C, and a rapid decline
      in I(opt) accompanies further increases in t beyond 25 degrees C. Such an
      asymmetric inverse V-shape I(opt)-t curve can be well described by Blanchard's
      equation. By this equation, I(opt) of each month was calculated based on monthly
      sea surface temperature, and though changes about 2 months later than light
      intensity above sea surface (I(0)), I(opt) is closely correlated with seasonal
      I(0) and transparency of sea water (R2 = 0.907 +/- 0.115, p < 0.001), which
      indicates that S. costatum adapts to the seasonality of light in sea water in the
      coastal area by varying I(opt) seasonally. Such an adaptive strategy leads to
      thick (about 6 m) light-optimal water layers for growth from early spring to late
      summer. The high adaptability to light and light optimum characteristics in sea
      water is one of the important reasons for S. costatum blooms in the both seasons
      in the coastal area in ECS.

PMID- 18828366
TI  - [Simultaneous removal of sulfide, nitrogenous compounds and organic carbon by
      anoxic attached-growth bioreactor].
AB  - By decreasing hydraulic retention times to increase substrates loading rates
      under anoxic conditions, an attached-growth bioreactor packed with porous sponges
      was started to treat the wastewater contaminated by sulfide, nitrate, nitrite and
      organic carbon. The influent concentrations of sulfide, nitrate-nitrogen, nitrite
      nitrogen and TOC were 200 mg/L, 52.5 mg/L, 20 mg/L, 20 mg/L and relevant removal
      efficiencies were 99%, 99%, 95.5% and 80% respectively. The simultaneous removal
      of nitrogenous compounds, sulfide and organic carbon was achieved by the
      desulfurization and denitrification process. With increasing of the substrate
      loading rates, the adaptabilities of nitrate and nitrite to the influent shock
      load decreased. The adaptability of nitrate to the shock load was better than
      that of nitrite. Compared with the impact on the bioreactor brought by the
      increasing of the influent shock load, the destruction of anoxic environment had
      greater influence on the degradation of nitrate and nitrite. 60% of the removed
      sulfide was converted to sulfur by microorganisms. The dominant reaction of
      autotrophic denitrification occurred together with the heterotrophic
      denitrification whose percent was 21.76%.

PMID- 18828367
TI  - [Control of shortcut nitrification in SBBR with adequate oxygen supply].
AB  - At the high level of dissolved oxygen (DO) in sequencing batch biofilm reactor
      (SBBR), the approach and mechanism for realizing shortcut nitrification were
      researched. Landfill leachate was used as handling of object, the mainly
      environment parameters of the reactor were controlled as follow: DO 5 mg/L, pH
      7.0, temperature 25 degrees C, adopted all drainage mode and 12-hour cycle
      influent. Through mathematical derivation and modeling analysis, determined free
      ammonia (FA), CO2 and HNO2 as the direct control factors, whereas the influent
      cycle time was the indirect one, shortcut nitrification was achieved effectively
      in SBBR. When the volume load of ammonia (NH4(+) -N) was 0.52 kg/(m3 x d) and
      NaHCO3 was 1.5 mg/L in the reactor, the shortcut nitrification effect was
      apparent as NH4(+) -N conversion rate was 89% and NO2(-) -N accumulation rate
      achieved 83% at the same time. With adequate oxygen supply, the key factors of
      achieving NO2(-) -N accumulation is FA concentration, and as the carbon source of
      ammonia-oxidizing bacteria, CO2 can upgrade the reactor performance further.

PMID- 18828368
TI  - [Biological phosphorus removal in sequencing batch reactor without anaerobic
      phase].
AB  - The performance of phosphorus removal with a sequencing batch reactor was
      investigated by simulated municipal wastewater. The experimental results showed
      that phosphorus removal could be achieved in sequencing batch reactor without
      anaerobic phase, which was conventionally considered as a key phase for
      phosphorus removal. Phosphorus concentration in the effluent was 1.0 mg x L(-1)
      below after 4 h aeration, during which pH was 7.0 +/- 0.2. Which indicated the
      removal rate of phosphorus was above 90% when the COD and phosphorus
      concentrationof influent were about 400 mg x L(-1), 15-20 mg x L(-1),
      respectively. Intracellular storage of poly-phosphate (poly-P) was increasing in
      the aeration after decreasing in first hour aeration (the content of poly-P was
      83.034 mg x g(-1) at the beginning of aerobic phase, 79.980 mg x g(-1) in first
      aeration and 83.086 mg x g(-1) in end), but the energy storage poly-beta
      hydroxyalkanoates (PHA) was constant nearly and the content was very low (PHA
      concentration was about 5 mg x L(-1)). The researches indicated that phosphate
      could be transformed to poly-P by poly-phosphate-accumulating organisms without
      anaerobic zone and PHA, biological phosphorus removal was obtained by removing
      sludge with rich phosphorus, and this phenomenon could not be explained by
      conventional theory.

PMID- 18828369
TI  - [Inhibitory effect kinetics of nitrite acting as electron acceptor on anoxic
      phosphorus uptake and denitrification].
AB  - Nitrite has been found in previous research an inhibitor on anoxic phosphorus
      uptake in enhanced biological phosphorus removal systems (EBPR). However, the
      inhibiting nitrite concentration reported varied in a large range and no kinetics
      study concerned on anoxic phosphorus uptake. This study investigates the nitrite
      inhibition on anoxic phosphorus uptake with sequencing batch reactor (SBR) in
      different concentrations of NO2- and under different pH gradient. The activated
      sludge was cultured with A2/O Oxidation Ditch pilot-scale reactor performing
      EBPR. The progress of SBR is as follows: the activated sludge was taken out an
      aerobic zone of the A2/O Oxidation Ditch to SBR, then phosphorus was released
      with acetate fed in anaerobic phase, subsequently phosphorus uptake proceeded
      with NO2- added in anoxic phase. It is pointed that not only NO2- but pH
      inhibited anoxic phosphorus uptake. The result indicated that (1) specific
      denitrification rate and specific phosphorus uptake rate correlated the original
      nitrite accord with Andrews's inhibition model under the constant pH. (2) If pH
      was in the range of 6.5 to 8.0, nitrite inhibited DPR much stronger when pH was
      less, vice versa. (3) Kinetics parameter was as follows: the max specific
      denitrification rate was 4.55 mg/(g x h), the half saturation constant of the
      denitrification process was 2.14 mg/L; and the max specific phosphorus uptake
      rate was 3.06 mg/(g x h), the half saturation constant of the phosphorus uptake
      process was 2.64 mg/L.

PMID- 18828370
TI  - [Effect of organic matter on phosphorus removal for substrate in constructed
      wetland].
AB  - Effect of organic matter (OM) on the phosphorus(P) removal efficiency for shale
      haydite in constructed wetland was investigated. At the conditions of hydraulic
      retention time 2 d, water flew in and out continuously, P concentration in water,
      its fractions in the substrate, and biomass in biofilm were analyzed. The results
      showed that the P removal efficiency for the substrates decreased with the
      increasing concentration of the OM, and that P sorption capacity for the
      substrate was inhibited by the OM. When COD in the influent were 100 mg/L and 200
      mg/L, P sorption capacity was decreased to 49% and 62%, labile organic
      phosphorus, Humic-P and Ca/Mg-bound P were significantly increased, Fe/Al-bound P
      was decreased from 36.75% to 18% and 11.77%. Thus, the result indicated that due
      to the OM accumulation, the portion of Fe/Al-bound P was low, and P sorption
      capacity was inhibited. In addition, the higher the concentration of OM is, the
      more biomass in biofilm is. The thickness of biofilm negatively correlated with
      mass transfer of phosphorus through the biofilm.

PMID- 18828371
TI  - [Denitrifying phosphorus-accumulating SBR combined with low-intensity aeration
      technology for piggery wastewater treatment].
AB  - The wastewater from animal farms in China is threatening the quality and security
      of local water environment. In the laboratory scale, a traditional SBR (A/O) and
      a denitrifying phosphorus-accumulating organisms (DNPAO) sequencing batch reactor
      (SBR) in biologically removing nutrients and organic matters from swine manure
      were investigated in this study. When piggery wastewater was directly treated
      with a traditional SBR, the efficiency was low with unstable working state, the
      reduction of TN, TP and BOD5 reached 89.08%, 86.04% and 93.88%, respectively.
      While it performs a good effect in treating high density of piggery wastewater
      using DNPAO SBR technology, with the help of low-density aeration, two-step of
      influent feeding and two circulations of anaerobic-anoxic-anaerobic-anoxic
      (An/Ax2), the reduction of TN, TP and BOD5 reached the maximums of 93.95%, 99.26%
      and 99.93%, respectively. The specific operation of (An/Ax2) SBR contributed both
      low concentrations and limited export loads of NO3-. The temporal curves of ORP,
      pH and DO over time could be indicators for simultaneous removals of nitrogen and
      phosphorus along with biodegradation of organic matter during this specific SBR
      running. A pilot-scale investigation was recommended to further testify the
      feasibility and efficiency of this kind of SBR under the real-world condition.

PMID- 18828372
TI  - [Effect of hydraulic load distribution on sewage treatment efficiency of
      earthworm bio-filter].
AB  - Effect of hydraulic load distribution on sewage treatment efficiency of earthworm
      bio-filter was studied by analyzing influent and effluent of earthworm bio-filter
      and earthworm behaviors. The results show that when hydraulic load varying from
      2.0 m3/(m2 x d) to 6.0 m3/(m2 x d), the concentration of each pollutant in
      earthworm bio-filter effluent increases slowly and is little effected by
      hydraulic load. When hydraulic load reaches 6.7 m3/(m2 x d), the concentration of
      COD, BOD5, SS, NH4(+) -N and TP in earthworm bio-filter effluent increases
      obviously, but the TN concentration in effluent presents descending tendency. The
      earthworms become rather inadaptable to the living conditions at this operating
      mode. As hydraulic load increasing, the earthworms' relative ingestive ability is
      improved at first, and then decreases. The earthworms' relative ingestive ability
      comes to the maximum at hydraulic load of 4.8 m3/(m2 x d), with good organic
      removal efficiency. The relation ships between hydraulic load and average weight,
      average density, unit-area biomass of the earthworms are significant negative
      correlation. The hydraulic load of 4.8 m3/(m2 x d) is recommended, but not over
      6.7 m3/(m2 x d).

PMID- 18828373
TI  - [Effect of humic acid and coexistent cation on the adsorption of Pb (II) in
      wastewater onto bentonite].
AB  - Both the physical-chemical properties and adsorption performance for lead of Na
      bentonite have been studied in this paper. The results showed that the removal of
      lead in solution by use of bentonite was effective. The pH, concentrations of
      coexistent cations and humic acid, which could influence the adsorption process
      were also studied. The results indicate that the sorption of lead (II) on Na
      bentonite increased as pH value increased, and increased with increasing humic
      acid concentration, while decreased with increasing coexistent cation
      concentration. The adsorption mechanism was investigated from thermodynamics, and
      it was founded that the sorption of lead (II) on Na-bentonite increased with
      increasing temperature and the Freundlich adsorption equation fit to the
      experimental data excellently. The thermodynamic parameters were calculated:
      deltaH = 0.959 4 kJ/mol, deltaS = 16.6113 kJ/(mol x K).

PMID- 18828374
TI  - [Coagulation characteristics of different Al species on humic acid removal from
      water].
AB  - Polyaluminum chloride PAC-Al13 with high Al13 content and PAC-Al30 with high Al30
      content were prepared. Coagulation behaviors of PAC-Al30, PAC-Al13 and AlCl3 for
      humic acid removal from water were compared by jar-test. The floc growth, the
      charge neutralization capacity, the effect of pH and coagulant dosage on
      coagulation efficiency were investigated, and the residual aluminium in the
      purified water was considered. The results show that the order of the floc
      formation capacity is PAC-Al30 > PAC-Al13 > AlCl3. PAC-Al30 and PAC-Al13 have a
      broader effective pH range of 5.0-8.0, compared with AlCl3. The difference of
      charge neutralization capacity between PAC-Al30 and PAC-Al13 is not significant,
      but PAC-Al30 performs a more effective coagulation at low coagulant dosages
      because of its stronger adsorption and bridging, and PAC-Al30 has a broader
      effective dosage range of 0.08-0.64 mmol/L, compared with AlCl3 and PAC-Al13. The
      humic acid removal reaches 98.5% at a pH of 7.0 and a PAC-Al30 dosage of 0.16
      mmol/L for the sample water with a humic acid content of 10 mg/L; and the
      residual aluminum in the purified water is 0.066 mg/L. The results verify that
      Al30 is another highly efficient coagulation/flocculation species for humic acid
      removal.

PMID- 18828375
TI  - [Efficiency of photodecomposition of trace NDMA in water by UV irradiation].
AB  - Efficiency of photodecomposition of trace NDMA by UV irradiation was investigated
      with analyzing the initial concentration of NDMA, solution pH, irradiation area,
      irradiation intensity and water quality effect on NDMA photolysis. NDMA could be
      effectively photodegraded by UV irradiation. The removal efficiency of NDMA was
      97.5% after 5 min of UV irradiation. Effect of initial NDMA concentration on
      photodecomposition of NDMA was not remarkable. With pH value ascending, the
      removal rate of NDMA photodecomposition decreased. The yields of photoquantum
      were more under lower solution pH than that under higher pH. NDMA had fastest
      reaction rate at solution pH = 2.2. Removal efficiency of NDMA increased with the
      available irradiation area ascending. Increscent ultraviolet irradiation
      intensity was good for NDMA degradation. Water quality affected the removal of
      NDMA slightly. The removal efficiency of NDMA in tap water and Songhua River raw
      water were 96.7% and 94.8%, respectively.

PMID- 18828376
TI  - [Degradation of simazine by O3/H2O2 system].
AB  - The endocrine disrupter simazine was oxidized by O3/H2O2 and the reactive
      productions was analyzed by chromatography to assess the degradation efficiency
      of Simazine. The initial content of Simazine 2 mg/L was removed about 87.1% by
      O3H2O2 system when the O3 was dosed as 10.0 mg/L, the H2O2/O3 molar ratio was
      0.70, the temperature was 26 degrees C and pH 7-8, which indicated Simazine could
      be conveniently removed by O3/H2O2 system in ordinary reactive condition. The
      simazine removal ratio in tap water was 10% more than it in purified water up to
      86.9%. The removal of simazine was decreased when the content of humic acid (HA)
      was high, whereas it was increased while low content HA in water. Also, the
      removal efficiency was inhabited by hydrogen carbonate fairly. The deethyl
      simazine (DES) was trapped by Gas Chromatography Mass Spectrum(GC-MS) which was
      also certificated by analyzing the Liquid Chromatography Mass Spectrum (LC-MS) of
      the products. The Ion Chromatography spectrum showed the existing of de-chloro
      procedure and breakage of triazine ring. Which indicated the oxidizability of
      O3/H2O2 system was fairly strong.

PMID- 18828377
TI  - [Radiolysis of chlorophenols in aqueous solution by gamma ray].
AB  - The radiolytic degradation of chlorophenols (CPs) in aqueous solutions by gamma
      radiation was studied. The effects of absorbed dose, different type of
      chlorophenol and their initial concentration on the degradation and
      dechlorination of CPs were investigated. The experimental results showed that
      gamma-irradiation was able to degrade CPs in aqueous solution successfully, and
      the radiolytic degradation of CPs was in accordance with the pseudo-first-order
      kinetic model. When the initial concentration of CPs was 100 mg x L(-1) and the
      radiation dose was 8 kGy, the removal efficiencies of 2-CP, 3-CP, 4-CP, 2,4-DCP
      were 68.0%, 97.5%, 89.7% and 100% respectively. The corresponding dechlorination
      efficiencies were 60.2%, 71.1%, 64.3% and 78.9%, respectively. The combination of
      radiation and O3/H2O2 resulted in a synergistic effect, which remarkably
      increased the degradation and mineralization efficiency of CPs.

PMID- 18828378
TI  - [Catalytic dechlorination of 2, 2', 3, 4, 4', 5, 5'- heptachlorobiphenyl in soil
      by Pd/Fe].
AB  - Dechlorination of 2, 2', 3, 4, 4', 5, 5'- heptachlorobiphenyl in soil was studied
      by using Pd/Fe bimetallic catalytic reduction. 2, 2', 3, 4, 4', 5, 5'-
      heptachlorobiphenyl can be dechlorinated effectively by Pd/Fe bimetal. It was
      found that the removal efficiency of 2, 2', 3, 4, 4', 5, 5'- heptachlorobiphenyl
      in soil could reach 54% after 5 days of reaction with 1 g of Pd/Fe (Pd loading
      0.05%) and at an initial pH of 5.6. Several important experiment parameters
      involved in this process were also studied, including Pd loading, initial soil
      pH, the reaction time, the amount of Pd/Fe used and 2, 2', 3, 4, 4', 5, 5'-
      heptachlorobiphenyl initial concentration. The results showed that higher Pd
      loading, higher dosage of Pd/Fe, lower initial concentration of 2, 2', 3, 4, 4',
      5, 5'- heptachlorobiphenyl and weak acid condition were beneficial to the
      catalytic dechlorination of 2, 2', 3, 4, 4', 5, 5'- heptachlorobiphenyl. The
      degradation of 2, 2', 3, 4, 4', 5, 5'- heptachlorobiphenyl, catalyzed by Pd/Fe,
      followed first-order kinetics, and the rate constant was 0.014 2/h, the half life
      was 49 h. In addition, two possible mechanisms of the dechlorination reaction
      were proposed and discussed.

PMID- 18828379
TI  - [Mechanism of enhancement on boron-doped diamond electrode electrochemical
      degradation efficiency by ultrasound].
AB  - Mass transport process, adsorption and desorption, and electrochemical reaction
      were analyzed to investigate the mechanism of enhancement on boron-doped diamond
      (BDD) electrode electrochemical degradation efficiency by ultrasound (US). US has
      considerable influences on the above steps of electrochemical oxidation. Mass
      transport coefficients of Ph and PA reach 2.0 x 10(-5) m/s with US, from 5.4 x
      10(-6)m/s and 6.7 x 10(-6) m/s in EC process, increasing by 270% and 199%,
      respectively. The effect of US on adsorption and desorption has relationship with
      electrochemical adsorption properties of pollutants on BDD electrode surface. The
      adsorption amount of Ph decreases from 6.49 x 10(-10) mol/cm2 to 1.39 x 10(-10)
      mol/cm2, with the desorption of polymer intermediates promoted, so US makes
      positive effect with benefit to direct oxidation and oxidation peak current
      increases by 32%. For PA, the adsorption amount decreases from 1.25 x 10(-11)
      mol/cm2 to 3.11 x 10(-12) mol/cm2 with US, and no direct oxidation happens in US
      EC process. US can improve degradation efficiency of BDD electrode and the
      enhancement on Ph degradation is more effective. Average electrochemical
      oxidation energy efficiency (AEE) of Ph increases by 287%, more than 224% of PA.
      This is because both direct and indirect oxidation for Ph can be enhanced by US,
      while for PA, direct oxidation almost disappears.

PMID- 18828380
TI  - [Deactivation mechanism of Pt anode in the process of electroxidation of p
      chlorophenol].
AB  - Deactivation of Pt electrode in the process of electroxidation of p-chlorophenol
      (p-CP) was investigated using linear sweep voltammetry, LC/MS and spectrum
      analysis techniques. The experiment results indicated that Pt would lose its
      electro-catalytic activity soon because polymer formed at the electrode surface.
      The in-site IR spectra of Pt showed two weak absorption bands appeared at 1 200
      and 1 800 cm(-1) during the oxidation of p-CP, which are characteristics of
      aromatic ether and carbonyl group, respectively. Increasing initial concentration
      of p-CP and pH value of solution would accelerate the deactivation speed of Pt.
      Acetonitrile lixivium for deactivated Pt was analyzed by LC/MS, and it was found
      that the polymers formed at the surface of Pt were some mixed compounds. The
      mechanism of polymerization includes the following ways: coupling reaction of
      organic radical each other; substituting reaction of organic radical with p-CP
      (or intermediates or small polymers).

PMID- 18828381
TI  - [Dynamitic development and evolution of redox zones in pollution plume].
AB  - A box filled with sandy soil was constructed to investigate dynamitic development
      and evolution of redox zones in landfill leachate-polluted plume. The results
      indicated that with time elapsing and pollution aggravating, redox zones moved
      ahead slowly; Methanogenic zone/ sulfate reduction zone extended gradually, and
      then inert zone appeared with further pollution. During the whole course of the
      dynamitic development and evolvement of redox zones, concentrations of TOC,
      sulfide, NH4(+) -N, HCO3-, CO2 and Fe2+ increased with time and decreased with
      distance; concentrations of NO3- and DO decreased with time and increased with
      distance; SO4(2-) concentration decreased first and then increased over time; but
      decreased with distance. Moreover, with time elapsing and pollution aggravating,
      the Fe3+ content of sediments was decrease and TOC was increase. Within oxygen
      reduction zone, nitrate reduction zone, iron reduction zone and methanogenic
      zone/sulfate reduction zone, Fe3+ content of sediments accounted for 70.5% of OXC
      decreased to 56.3%, 41%, 28.3% and 15%, and the TOC accounted for 98.7% of RDC
      increased to 102.0%, 107.0%, 142.9% and 162.1%, respectively; Fe2+ mainly
      precipitated as FeS and FeCO3, and accounted for 80.6%, 175.6%, 377.7% and 555.1%
      of total Fe2+, respectively.

PMID- 18828382
TI  - [pH buffering capacity of geological media on landfill leachate].
AB  - The one-dimensional breakthrough soil column experiment and static experiment
      were constructed to investigate the spacial and temporal pH buffering capacity of
      the four natural geological media. Experimental results indicate that the
      background pH buffering capacity of fine sand, silt sand and clay is 79.9 x pH(
      1) mmol/kg, 207.5 x pH(-1) mmol/kg, 456.4 x pH(-1) mmol/kg respectively. With the
      time going on and the distance closer to the leaching source, for each medium
      which is contaminated by the landfill leachate, the total pH buffering capacity
      decreases, the buffering capacity of calcium carbonate buffering system
      decreases, the buffering capacity of the silicate and cation exchange buffering
      system have no obvious changes, and the buffering capacity of the aluminium and
      ferric oxide buffering system also decrease, but the soil's buffering capacity of
      aluminium buffering system increases at first and then decreases. The temporal
      and spacial buffering capacity for each buffering system of the fine sand all
      increase appreciably. The order of the pH buffering capacity of the geological
      media on landfill leachate is fine sand < silt sand < clay < soil. The soil and
      clay have a good pH buffering capacity on landfill leachate as well as the
      controlling effect of the pollutants' transferring and diffusion.

PMID- 18828383
TI  - [Removal characteristic of pathogenic protozoan in wastewater treatment and
      reclamation process].
AB  - The concentration of pathogenic protozoan (Cryptosporidium and Giardia) in water
      samples of different units in a full-scale wastewater treatment plant in Beijing
      was investigated periodically. The average concentrations of Cryptosporidium
      detected in untreated wastewater, primary sedimentation, secondary sedimentation,
      flocculation-sedimentation and sand-filtration effluent were 238, 179, 6, 1, 0.3
      oocysts/L respectively, and the average concentrations of Giardia were 1568,
      1048, 22, 4, 0.6 cysts/L respectively. The total removal efficiencies of
      Cryptosporidium and Giardia in this treatment process were 2.98 and 3.46 log
      respectively. Very little protozoan in wastewater could be removed by preliminary
      treatment process, the removal efficiencies were only 0.13 and 0.18 log
      respectively. Biological treatment unit had the highest removal efficiency, up to
      1.50 and 1.67 log respectively. Advanced treatment process could enhance the
      removal of the protozoan effectively. The results also showed that the pollution
      level of pathogenic protozoan in the influent of wastewater treatment and
      reclamation plant was various according to the climate, high in dry seasons and
      low in rainy season.

PMID- 18828384
TI  - [Biodegradation mechanisms of 17beta-estradiol (E2) by lake sediment].
AB  - Batch experiments using lake sediment mud liquors spiked with E2 were performed
      under aerobic and anaerobic conditions. The catabolic mechanisms of E2 were also
      induced. The results indicate that under aerobic condition, 99% of E2 can be
      removed from aqueous phase after as short as 24 h. Concentration of estrone (E1)
      firstly increase and then decrease slowly until to vanish from aqueous phase;
      Under anaerobic condition, 4% of E2 still be in aqueous phase after 96 h of
      reaction. Concentration profile of E1 show that E1 firstly increase then
      decrease, then increase and then decrease to vanish from aqueous phase finally.
      Analyzing the concentration profiles of E2 and E1, we draw a conclusion that E2
      is oxidized to E1 by dehydrogenase and then E1 was oxidized by other enzymes
      within sediment to mineralization completely under aerobic condition. Under
      anaerobic condition, there is a mutual translation relation between E2 and E1. E2
      was oxidized to E1 by dehydrogenase and synchronously E1 is reduced to E2. During
      this mutual translation course, E2 and E1 can be degraded gradually to finally
      mineralization completely by other enzymes within the reaction system. Comparing
      with E2, E1 can accumulate more easily within biosolid in natural waters.

PMID- 18828385
TI  - [Effects of low concentration heavy metals on biodegradation of BDE209 by
      Bacillus cereus].
AB  - In view of joint contamination of heavy metals and polybrominated diphenyl ethers
      (PBDEs) caused by electronic-wastes, analysis measures of GC-MS, ICP, UV
      scanning, fTIR, SEM, etc. were used to research on the debromination of deca
      brominated diphenyl ethers (BDE209) and biodegradation capability under aerobic
      condition by combined Bacillus cereus XPB and XPC, and the effects of low
      concentrations of heavy metals on the biodegradation of BDE209 were also studied.
      The experimental results showed that combined Bacillus cereus efficiently
      debrominated and degraded BDE209 to hydroxybenzenes, and the highest
      debromination capability of 1.18 mg x L(-1) with the efficiency of 14.16% at
      least was achieved after 1 d reaction. Although biodegradation process was
      delayed at presence of low concentrations of heavy metals, satisfying degradation
      effect was still achieved with debromination efficiency of not less than 13.92%.
      Hydroxy, a minoacyl, and alkyl were confirmed to be the key functional groups for
      combined Bacillus cereus to biodegrade BDE209 and adsorb heavy metals. Obvious
      release of K+ and Na+ was observed and the release quantity rose up from 148.867
      micromol x g(-1) and 225.835 micromol x g(-1) respectively, when only
      biodegradation was involved, to 156.482 micromol x g(-1) and 261.217 micromol x
      g(-1) individually when biodegradation and biosorption acted simultaneously.
      During the process of BDE209 biodegradation, the highest adsorption rates for
      Pb2+, Zn2+, and Cu2+ by combined Bacillus cereus were 89.47%, 72.22% and 39.83%
      respectively.

PMID- 18828386
TI  - [Construction of a stable genetically engineered microorganism for degrading HCH
      & methyl parathion and its characteristics].
AB  - A GEM designated as BHC-A-mpd, capable of simultaneously degrading of methyl
      parathion (MP) and HCH was successfully constructed by random insertion of a
      methyl parathion hydrolase gene (mpd) into chromosome of a HCH-degrading strain
      BHC-A with the mini-Tn-transposon system. The growth and degrading
      characteristics of BHC-A-mpd was compared with the original strain BHC-A, and the
      result showed that there was no difference in this two aspects, A600 nm of BHC-A
      mpd in LB medium could reach 2.5 in logarithmic period, which was the same as
      that of the original strain BHC-A.BHC-A-mpd showed the same HCH-degrading ability
      as BHC-A and could degrade 5 mg/L of gamma-HCH in 10 h. BHC-A-mpd showed high
      genetica stability and could degrade many kinds of organophosphorus pesticides.
      All these results indicated that BHC-A-mpd was a promising GEM in bioremediation
      of MP and HCH co-contaminated environment.

PMID- 18828387
TI  - [Biodegradation of nonylphenol ethoxylates by a bacterial strain with
      heterotrophic nitrogen removal ability].
AB  - Biodegradation of nonylphenol ethoxylates (NPEOs) by Bacillus sp. LY with
      heterotrophic nitrogen removal ability was investigated. The study showed that
      Bacillus sp. LY could biodegrade NPEOs largely combined with heterotrophic
      nitrogen removal. After 14 d, removal efficiency of NPEOs was 95.6% and removal
      rates of TN was 43.9%. Biodegradation of NPEOs by the strain Bacillus sp. LY
      conformed to the first-order kinetic model, with biodegradation rate constant
      0.224 d(-1). NPEOs were biodegraded through a nonoxidative pathway with
      sequential removal of ethoxyl units. Moreover,no more harmful nonylphenoxyacetic
      acids were formed by this pathway. NPEOs could be degraded by Bacillus sp. LY in
      the presence of different nitrogen contaminants NH4 Cl, NaNO3 and NaNO2. The
      removal efficiency of NPEOs was highest in the presence of ammonium. Results may
      make contribution to the efficient removal of compound contamination of NPEOs and
      nitrogen contaminants.

PMID- 18828388
TI  - [Effect of Mn2+ on pyrene degradation by Flavobacterium sp. FCN2].
AB  - Mn2+ concentration affecting polycyclic aromatic hydrocarbon pyrene degradation
      by the Flavobacterium sp. FCN2 was investigated by adding Mn2+ during several
      periods, which including bacteria cultivation period, bacteria degrading pyrene
      and enzymatic degradation period. Results show the concentration of Mn2+ was
      beneficial for pyrene degradation, and Mn2+ was no influential to bacteria growth
      and magnitude. When Mn2+ was added during culturing strain FCN2 period, bacteria
      FCN2 can enrich Mn2+, and pyrene removal efficiency by Mn2+ enrichment bacteria
      is 1.26 times more than that of without Mn2+ enrichment bacteria. As well as the
      situation that adding Mn2+ during FCN2 degrading pyrene period that pyrene
      removal efficiency is 1.67 times more than that of without Mn2+. And when adding
      Mn2+ during enzymatic degradation periods, the elimination efficiency of pyrene
      was 1.30 times more than that of without Mn2+.

PMID- 18828389
TI  - [Enhanced biodecolourization of azo dyes by the catalysis of anthraquinone dyes
      intermediators].
AB  - Enhanced biodecolourization of azo dyes by suspended and immobilized quinone
      reducing community using kinds of anthraquinone dyes intermediators as redox
      mediators was investigated. The suspended bacterium community could enhance the
      biodecolourization of many kinds of azo dyes using bromoamine acid (BAA) as a
      redox mediator, the optimum conditions for Acid Red 3R were as follows: pH 6-9,
      glucose, BAA and initial dye concentrations 400-600 mg/L, 19-34.2 mg/L and < or =
      900 mg/L, respectively. Under these conditions, the maximal decolourization rate
      was about 95%, which is reached within 7 h for suspended cells and 14 h for
      immobilized cells. However, the latter needed 38-57 mg/L BAA as a redox mediator.
      In addition, after 7 cycles without BAA addition, the decolourization rate of
      Acid Red 3R by immobilized cells retained over 85%.

PMID- 18828390
TI  - [Analysis of microbial community in a deodorization biofilter by PCR-sSCP
      method].
AB  - Microbial community of biofilm in a biofiltration was investigated using PCR-SSCP
      (single strand conformation polymorphism) technique in this paper. The results
      indicated the removal rate of odor pollutants improved with the acclimation, from
      50% to 89%, and the microbial diversity of biofilter decreased at the first month
      and then increased (diversity index H from 1.6-1.9 to 2.0) while the similarity
      gradually increased during the operation time. Higher microbial diversity (H =
      2.2) in cortex indicated the microorganisms were easily attached to the media
      compared to the straw (H = 2.0). Dominant bacteria were Bacillus found in the
      biofilm using SSCP method, and the rate is 33.3%. 44.4% of the total bands
      represented the uncultured bacteria. These bacteria are widely existed in soil,
      water and nature environment, they have good acclimatization to environment and
      played important role in treating odors. The biofilm development was identified
      by the scanning electron microscopy (SEM), which suggested that the microbial
      community in biofilter could grow by utilizing pollutants and become rich and
      stable with running time.

PMID- 18828391
TI  - [Effect of Tween 80 and rhamnolipid on enzymatic hydrolysis of straw].
AB  - The method of enzymatic hydrolysis was adopted and straw was used as substrate to
      study the effects of reducing sugar yield, enzyme stability and convention rate
      of cellulose during the course of enzymatic hydrolysis as well as the impacts of
      enzyme kinetic characteristics and adsorption of cellulase on cellulose by
      addition of chemical-surfactant Tween 80 and biosurfactant rhamnolipid. The
      results indicated that Tween 80 and rhamnolipid at different concentrations
      enhanced the production of reducing sugar. Tween 80 at 0.016% and 0.048%
      increased reducing sugar yield by 18.07% and 11.98%, while rhamnolipid at 0.01%
      and 0.03% increased reducing sugar yield by 23.01% and 22.16%, respectively. It
      can be seen from the experimental results that surfactants improved enzyme
      stability availably. Surfactants at high concentrations were superior to those at
      low concentrations in enzyme stability. Tween 80 at 0.048% obtained maximal
      relative carboxymethylcellulose activity (CMCA) 108.06% and maximal relative
      filter paper activity (FPA) 80.26%. Surfactants also enhanced conversion rate of
      cellulose, and that in the present of rhamnolipid, the percent conversion of
      cellulose was higher than those with Tween 80 distinctly. Moreover, surfactants
      not only promoted maximal velocity of enzymatic reaction and largened Michaelis
      constant but also reduced adsorption of cellulase on cellulose remarkably.

PMID- 18828392
TI  - [Mixture effects to vitellogenin induction by four environmental estrogens in
      freshwater fish].
AB  - Combined effects of estrogenic compounds to high risk life-form were
      demonstrated, and the study method on combined effects of environmental
      contaminant mixture and environmental risk assessment were also discussed. A
      nonlinear aggression was determined on the changes of plasma vitellogenin
      concentration in crucian carp via the environmental pollutant exposure
      concentration, and the concentration-response relationship was determined for the
      single chemical of estradiol, ethynylestradiol, bisphenol A, and octylphenol, and
      that of the mixed compounds at equipotent concentrations. The combined effects of
      the four xenoestrogens were tested using indices of mixture toxicity and the
      biomathematical models of concentration addition or independent action. Weibull
      function was indicated as the best-fit function (R2 > or = 0.92) with curve
      estimation, the 95% confidence limits of effect concentration was achieved using
      the bootstrap method, the media effective concentration (EC50) with 95%
      confidence interval was 0.007 9 (0.006 8-0.010 0), 0.098 7 (0.090 0-0.111 0),
      63.50 (56.58-70.62) and 250.59 (228.46-271.99) Mg x L(-1) respectively. Results
      suggested that estrogenic chemicals acted together in an additive manner and the
      combined effects can be accurately predicted in whole range of exposure
      concentration by the concept of similar joint action or concentration addition.It
      is proved as a scientific and feasible method to apply the model of joint action
      whereas the outcome of indices with a great deal of indetermination.

PMID- 18828393
TI  - [Oxidation stress and toxicity of TBBPA pollution on polychaete tubifex
      (Monopylephorus limosus)].
AB  - Using the indoor simulating method of dynamic and static exposure respectively,
      the toxic effects of TBBPA on the antioxidant enzyme defense systems and
      Glutathione-S-transferase (GST) activity of tubifex Monopylephorus limosus were
      examined. The activity of superoxide dismutase (SOD) and catalase (CAT) with time
      was also examined. The results showed that after an 8 d exposure, the SOD
      activity was enhanced at first and then inhibited gradually, at last enhanced
      again. The highest activity of SOD (p < 0.01) was examined under 0.05 mg/L
      concentration of TBBPA. And the activity of SOD was much higher than that of
      control (1.5-7.8 times more than that of the control). The activity of CAT showed
      a tendency of induction firstly and then inhibition, then induction again and at
      last inhibition, reached the highest value under 0.5 mg/L of TBBPA. Furthermore,
      the CAT activity was higher than that of the control (1.1-1.9 times more than
      that of the control) except that under 0.005 mg/L and 0.25 mg/L of TBBPA.
      Moreover, the highest activity of GST (p < 0.01) was observed under 0.25 mg/L of
      TBBPA. The activity of GST was enhanced gradually at first and then inhibited. As
      the same as SOD, the activity of GST was induced significantly (p < 0.05). The
      changes in the SOD activity showed an "M" trend,while that in the CAT activity
      showed an "N" trend. And the activity of SOD is steadier than that of CAT. Thus,
      changes in the activity of SOD and GST, especially SOD, can better reflect the
      toxic effects of pollutants on tubifex.

PMID- 18828394
TI  - [Influences of pine needles physiological properties on the PAH accumulation].
AB  - The lipid contents, specific surface areas and stomata density of two kinds of
      pine (Cedrus deodar and Pinus thunbergii) needles were determined simultaneously
      with the levels of polycyclic aromatic hydrocarbons (PAHs). The influences of the
      physiological properties of two species on the accumulation of PAHs in pine
      needles were investigated. The PAH concentrations in Cedrus deodar needles are
      higher than that in Pinus thunbergii needles, and the average total PAH
      concentrations (PAHs) in two species are (1 101 +/- 692) ng/g and (518 +/- 339)
      ng/g, respectively. The capabilities of accumulating PAHs for two species are
      different. The lipid content is the principal factor influencing the levels of
      pine needle PAHs. In Cedrus deodar and Pinus thunbergii needles, 3-ring (> 56%)
      and 4-ring (> 31%) PAHs make up large proportions of sigma PAHs. The accumulation
      capabilities of pine needles for 3-ring PAHs are greater than 4-ring PAHs, and
      the concentrations of 3-ring PAHs are about two times of those of 4-ring PAHs.
      There are no significant correlations between the levels of 5- and 6-ring PAHs
      and lipid contents for two species. For two species, the correlations between
      lipid contents and specific surface areas are different, which results in the
      contrary correlations between the PAH levels and specific surface areas for
      Cedrus deodar and Pinus thunbergii. Specific surface areas and stomata density
      affect the levels of 5- and 6-ring PAHs in pine needles significantly.

PMID- 18828395
TI  - [Effect of lanthanum on the flavonoids contents and antioxidant capacity in
      soybean seedling under ultraviolet-B stress].
AB  - Dynamic state of antioxidant capacity of flavonoids was investigated for a
      further demonstration of alleviating the damage of the UV-B radiation in the La
      treated soybean seedlings under UV-B stress. Using hydroponics culture, the
      effects of lanthanum on the contents of flavonoids and its ability of antioxidant
      under elevated ultraviolet-B radiation (280-320 nm) was studied in this paper.
      The results showed flavonoids contents in Soybean seedlings during the stress and
      convalescent period increase firstly and then reduce. Membrane permeability and
      MDA contents increase firstly (1st-5th day) and then fall (6th to 11th day). A
      similar change of flavonoids contents and clearance of flavonoids scavenging O2*-
      and *OH in soybean seedlings occur; the flavonoids contents La(III) + UV-B > UV-B
      > La(III) > CK, La(III) + T1 > La(III) + T2. Plasma membrane permeability and MAD
      contents UV-B> La(III) + UV-B > CK > La(III), La(III) + T2 > La(III) + T1. The
      ability of Scavenging activities of free radical (O2*-, *OH) La(III) + UV-B > UV
      B > La(III) > CK. It suggested that the regulative effect of La(III) on
      flavonoids, improved the metabolism of ROS, diminished the concentration of MDA
      and maintained normal Plasma membrane permeability, and that its protective
      effect against low UV-B radiation was superior to that of high UV-B radiation. To
      conclude, the defensive effect of La(III) on soybean seedlings under UV-B stress
      was carried out on the layer of defense system.

PMID- 18828396
TI  - [Effects of cadmium and lead on subcellular distribution and chemical form of
      zinc in Potentilla griffithii var. velutina].
AB  - Using the differential centrifugation technique and sequential chemical
      extraction method, effects of Cd, Pb and different Zn salts on subcellular
      distribution and chemical form of Zn in Zn hyperaccumulator Potentilla griffithii
      var. velutina under nutrient solution culture were analyzed. Under all treatments
      except for the control, 46%-74% and 16%-33% of total Zn in the plants are
      distributed in cell wall and in soluble fraction, respectively. Further, 74%-95%
      of total Zn are localized in these two parts under all treatments, which suggest
      that cell wall and soluble fraction in the plant are major storage sites for Zn.
      Compared with the control, Zn percentage significantly increases by 9%-38% in the
      cell wall and decreases by 6%-40% in the soluble fraction with addition of Zn, Cd
      and Pb treatment (p < 0.05). Although the addition of Cd and Pb has no influence
      on the pattern of Zn subcellular distribution presenting cell wall > soluble
      fraction > karyon and chloroplast > mitochondrion, it generally reduces Zn
      percentage in the chloroplast, karyon and mitochondrion and increases that in the
      cell wall or soluble fraction, suggesting that Cd and Pb promote the transferring
      processes of Zn from organelle to either cell wall or vacuole. As to the chemical
      forms, 61%-87% of total Zn exist as ethanol- and water-extractable forms in
      plants under control and only leaves under Zn addition treatment; while 62%-73%
      of total Zn exist as NaCl- and ethanol-extractable forms in leafstalks and roots
      under Zn addition treatment. NaCl-, ethanol- and water-extractable forms are also
      the main chemical forms in the plants, occupied almost 70%-89% of total Zn under
      Zn/Cd and Zn/Pb compound treatments. The addition of Zn, Cd and Pb generally
      increases the percentage of NaCl-extractable Zn forms, but decreases that of
      ethanol-extractable Zn, which facilitates Zn chemical form transferring from
      relatively higher active forms to less active ones. These results mentioned above
      indicate that cell wall binding, vacuolar compartmentalization and reduction of
      total percentage in higher active chemical forms are main tolerance mechanisms
      for Zn in Potentilla griffithii var. velutina in response to Zn, Zn/Cd and Zn/Pb
      treatments. Additionally, different Zinc salts have no obvious influence on Zn
      subcellular distribution in the plant, whereas the treatment of Zinc nitrate
      turns Zn ethanol-extraction to a dominant chemical form.

PMID- 18828397
TI  - [Effects of different irrigation and nitrogen supply levels on nitrate-N dynamics
      in a recently reclaimed sandy farmland in Heihe River basin].
AB  - Improper nitrogen (N) and irrigation management are major causes leading to
      deterioration in water environmental quality in the middle reaches of Heihe River
      basin. A controlled experimental study of different irrigation and N supply
      levels was therefore conducted in the Linze Inland River Basin Research Station,
      Chinese Academy of Sciences, to determine the influences of N addition and
      irrigation regime on the dynamics of nitrate-N (NO3(-) -N) distribution in soil
      profiles over the growing season of spring wheat. The experiment employed a
      completely randomized block split-plot design, with irrigation treatments [0.6,
      0.8, 1.0 of the estimated evapotranspiration (ET), denoting I0.6, I0.8 and I1.0
      respectively] and N addition treatments [0, 140, 221, 300 kg x hm(-2), denoting
      N0, N140, N221 and N30 respectively] as the main-plot and split-plot,
      respectively. Our results show that the rate of N is the key factor in
      influencing NO3(-) -N content and its leaching. The content of NO3(-) -N in the 0
      200 cm soil profiles was found to increase with increased N rates, and in
      particular this increase was more pronounced when the N rates ranged between 221
      kg x hm(-2) and 300 kg x hm(-2). In addition, NO3(-) -N leaching is relatively
      less apparent at the N rates in the range of 0-140 kg x hm(-2), but this effect
      became significant when the N rates exceeded 140 kg x hm(-2). Our results also
      show that NO3(-) -N contents were generally higher at the anthesis stage than at
      the harvest stage within the same soil layer. The observed differences in NO3(-) 
      N contents between the irrigation treatments of I0.6, I0.8 and I1.0 were
      insignificant across N rates. This finding suggests that N addition treatments
      may have greater impacts on NO3(-) -N leaching than irrigation treatments.
      Although the among-irrigation differences of NO3(-) -N contents within the same
      soil layer varied with N level, there was a tendency that NO3(-) -N content of
      I1.0 treatment was significantly lower than that of I0.8, and that of I06
      irrigation treatment in the soil layer with significant differences in N
      contents. This result suggests declined NO3(-) -N leaching with decreased
      irrigation levels.

PMID- 18828398
TI  - [Spatial pattern of sand-mound of Nitraria in different habitat at the
      southeastern fringe of the Tengger desert].
AB  - Based on the geo-statistics and quantitative ecology method, the spatial pattern
      of sand-mound of Nitraria was been analyzed in different habitat at the
      southeastern fringe of the Tengger desert in order to keep the natural mounds
      stability and ecological efficiency. The results showed that the different
      groundwater level and plant growth condition resulted in difference of Nitraria
      population at capacity of withstanding sand bury and the effect of sand-binding.
      The coverage, density and biomass of Nitraria population at the lacustrine basin
      lowland were significant higher than those of the alluvial fan (p < 0.01).
      Although the height of Nitraria population at the lacustrine basin lowland was
      lower than that of the alluvial fan, there was no significant difference between
      two habitat (p > 0.05). The height and volume of sand-mound was 1.20 m and 88.19
      m3 at the lacustrine basin lowland, 1.14 m and 33.16 m3 at the alluvial fan,
      respectively. The size and distribution of sand-mound was significant difference
      at different habitat (p < 0.01). The mound of the lacustrine basin lowland has
      the tendency of large patch and low density, developed longer scale pattern in
      auto-correlated distance, and those of the alluvial fan just the reverse. The
      spatial heterogeneity of mound size and volume of accumulation sand in the
      lacustrine basin lowland can be controlled by auto-correlated factors at 1.2-84 m
      scale, and the random factors at under 100 m controlled the spatial heterogeneity
      in the alluvial fan. Especially, the size and volume of sand-mound has constant
      variation at under the 100 m scale in the alluvial fan, and has random spatial
      pattern without law.

PMID- 18828399
TI  - [Influence of aging on the extractability and bioavailability of
      hexachlorocyclohexane (HCH) in soil].
AB  - Influence of aging on the extractability and bioavailability of HCHs (alpha-,
      beta, gamma- and delta- isomers) in paddy soil were investigated in the lab under
      simulated circumstances. Results indicate that extractable HCHs decreased as
      their contact time with soil increased. The aging rate of HCHs in soil was rather
      high at the initial stage, and then slowed down in the rest of the time. During
      the first 60 days aging period, alpha-HCH, beta-HCH, gamma-HCH and delta-HCH
      dropped off 57.2%, 50%, 52.2% and 43.2% of the initial concentrations, about
      90.5%, 87.4%, 72.4% and 84.4% of the total quantity of HCHs decreased in 180 d
      respectively due to high aging rate. Bioaccumulation of HCHs in earthworm
      displayed the same rule as aging, that is, the contents of HCHs in earthworm
      decreased as the incubation time extended, and so did bioaccumulation factors
      (BAF). The contents of HCHs accumulated in earthworm showing the order of alpha
      HCH > beta-HCH > delta-HCH > gamma-HCH, while the accumulative ability expressing
      the rule of gamma-HCH > alpha-HCH > beta-HCH > delta-HCH in the first 15 d, and
      then alpha-HCH > beta-HCH > gamma-HCH > delta-HCH in the rest incubation time.
      Though the extractable HCHs decreased with aging, they still can be accumulated
      in earthworms, thus posing potential risk to soil environment.

PMID- 18828400
TI  - [Volatilization behavior of BTEX on different underlying materials].
AB  - Volatilization behavior of benzene, toluene, ethylb-enzene and xylene (BTEX)
      behaves complicatedly with different characteristics of the underlying materials.
      For the need to control and take precautions against volatile organic compounds
      (VOCs) leak and pollution, and consider the diversification of underlying
      materials in the area of petroleum works, the test was carried out to study the
      volatilization behavior of BTEX on three kinds of typical underlying materials in
      Zibo, Shandong, China. The studies include volatilization dynamic curves of BTEX
      compounds and mixture and the optimized simulation formulas for them in the base
      of volatilization kinetics model. The results indicated that, under the same
      condition, volatility speed of BTEX compounds and mixture was Benzene > Toluene >
      BTEX > Dimethyl-benzene > Ethylbenzene, and for the three underlying materials,
      the order of volatility speed was water, sand and soil in sequence. The
      volatility coefficient linear positive correlated with the vapor pressure, the
      volatility coefficient remarkably increased with the vapor pressure of BTEX
      compounds on all the three underlying materials. The mechanism of underlying
      materials acted on volatilization of BTEX were mainly shown as increasing
      volatility area and influence the available original (amount) of pore in the
      course of volatilization and spread.

PMID- 18828401
TI  - [Components of oil sludge and their influence on pyrolysis behaviors].
AB  - Based on property analysis of oil sludge and its main components (mineral oil and
      minerals), pyrolysis process and releasing behavior of non-condensed gas of oil
      sludge and its main components were studied by thermogravimetric analysis-fourier
      transform infrared spectroscopy (TG-FTIR) and tubular resistance furnace,
      respectively. The results indicated that, (1) Oil sludge was characterized as
      relatively high heating value (15 422.41 kJ/kg), higher mineral content (61.57%)
      mainly composed of quartz. Mineral oil component had good thermal conversion
      property and adhered close with mineral in oil sludge. (2) Pyrolysis process of
      oil sludge included 5 stages: water volatilization and gas desorption (50-180
      degrees C), light oil volatilization (180-370 degrees C), heavy oil pyrolysis
      (370-500 degrees C), semi-coke charring (500-600 degrees C) and mineral
      decomposition (higher than 600 degrees C). (3) Minerals influenced oil pyrolysis
      by surface function and enhancing heating conductivity, meanwhile minor elements
      in mineral oil could bring mineral decomposition temperature down. (4) Minerals
      affected the releasing behavior of non-condensed gas from mineral oil pyrolysis
      and resulted in lower total production and higher H2 production.

PMID- 18828402
TI  - [Principal physicochemical properties of artificial soil composed of sewage
      sludge stabilized by fly ash].
AB  - The pH, nutrients and heavy metals of stabilized sewage sludge were investigated
      by mixing municipal sewage sludge with alkaline fly ash and mine tailing. The
      results indicate that water-holding capacity of artificial soil III (FA : SS = 1
      : 1) and II (FA : SS = 2 : 1) treatments were significantly higher than that of
      CK (brown meadow soil), while that of the IV (FA : SS = 1 : 2) treatment was
      similar to CK; The nutrients contents (organic matter, N, P, K) of stabilized
      sewage sludge were up to a high fertilizer level. Moreover, with decrease of the
      ratio of fly ash to sewage sludge, the nutrient content of artificial soils
      increased. Except total Ni content of III (FA : SS = 1 : 1) treatment was high
      (187.67 mg x kg(-1)), Cd, Pb, Cu, Zn, and Cr for all artificial soil treatments
      were all significant lower than control standards for pollutants in sludges and
      fly ash from Agricultural use (GB 4284-84, GB 8173-87).

PMID- 18828403
TI  - [Phosphate transform of composting with pre-mixing insoluble phosphate using high
      temperature dissolved phosphorus microbes inoculation].
AB  - In order to enhance the available phosphorus (P) of compost production, the
      experimental design of composting included three treatments was conducted. The
      treatments were: Control (CK) with no dissolved phosphate microbes inoculation,
      no rock phosphate mixing; CP with no dissolved phosphate microbes inoculation,
      rock phosphate mixing; CMP with dissolved phosphate microbes inoculation, rock
      phosphate mixing. At different composting phases, the samples were taken for the
      determination of phosphorus forms. Compared to CK, organic P, dissolved P and
      rapidly available P of CP increase by 2 049.8, 264.2, 954.0 mg/kg at final stage
      of composting, respectively; while that of CMP increase by 4 188.6, 648.7, 3
      576.4 mg/kg, respectively. The increase of organic P, dissolved P and rapidly
      available P in CMP is 2.04, 2.46, 3.75 times as that of CP, respectively. The
      results indicated dissolved phosphate microbes inoculation composting with pre
      mixing rock phosphate would accelerate transform efficiency of insoluble
      phosphate, increase the available P of compost production.

PMID- 18828404
TI  - [Framework of regional environmental monitoring and early-warning system].
AB  - Environmental monitoring and early-warning system should be built to enhance the
      capacity of environmental monitor and management. Risk knowledge, monitoring and
      early-warning service, dissemination and communication, and response capacity are
      functional modules to achieve the management object. When constructing a regional
      environmental monitor and early-warning system, institution for monitor and
      management, laws and regulations, equipments, persons with ability, information
      system, consultation capacity and service system for public participation should
      be contained to build the monitor and early system.

PMID- 18828405
TI  - The importance of making healthy choices before having sex.

PMID- 18828406
TI  - Preterm birth as a public health initiative.

PMID- 18828407
TI  - Leprosy: praise and concern.

PMID- 18828408
TI  - Reducing toxic chemical levels in cigarette smoke.

PMID- 18828409
TI  - Adopting competencies for a graduate school curriculum in epidemiology.

PMID- 18828410
TI  - Disaster mythology and fact: Hurricane Katrina and social attachment.
AB  - Misconceptions about disasters and their social and health consequences remain
      prevalent despite considerable research evidence to the contrary. Eight such
      myths and their factual counterparts were reviewed in a classic report on the
      public health impact of disasters by Claude de Ville de Goyet entitled, The Role
      of WHO in Disaster Management: Relief, Rehabilitation, and Reconstruction
      (Geneva, World Health Organization, 1991), and two additional myths and facts
      were added by Pan American Health Organization. In this article, we reconsider
      these myths and facts in relation to Hurricane Katrina, with particular emphasis
      on psychosocial needs and behaviors, based on data gleaned from scientific
      sources as well as printed and electronic media reports. The review suggests that
      preparedness plans for disasters involving forced mass evacuation and
      resettlement should place a high priority on keeping families together--and even
      entire neighborhoods, where possible--so as to preserve the familiar and thereby
      minimize the adverse effects of separation and major dislocation on mental and
      physical health.

PMID- 18828411
TI  - The Saskatchewan Farm Injury Cohort: rationale and methodology.
AB  - The Saskatchewan Farm Injury Cohort (SFIC) is a major new Canadian study that was
      developed to evaluate potential causes of injury among farmers and their family
      members. The cohort involves 2,390 farms and 5,492 farm people being followed
      over a two-year period. The article describes the rationale and methodology for
      the baseline and longitudinal components of this study. The SFIC is one of the
      first studies to apply population health theory to the modeling of risks for
      injury in a defined Canadian population. In doing so, the relative influence of
      several potential causes of farm injury, including physical, socioeconomic, and
      cultural factors, will be estimated. Study findings will inform the content and
      targeting of injury prevention initiatives specific to the farm occupational
      environment.

PMID- 18828412
TI  - Place matters: variation in the black/white very preterm birth rate across U.S.
      metropolitan areas, 2002-2004.
AB  - OBJECTIVE: We reported on the distribution of very preterm (VPT) birth rates by
      race across metropolitan statistical areas (MSAs). METHODS: Rates of singleton
      VPT birth for non-Hispanic white, non-Hispanic black, and Hispanic women were
      calculated with National Center for Health Statistics 2002-2004 natality files
      for infants in 168 MSAs. Subanalysis included stratification by parity, age,
      smoking, maternal education, metropolitan size, region, proportion of MSA that
      was black, proportion of black population living below the poverty line, and
      indices of residential segregation. RESULTS: The mean metropolitan-level VPT
      birth rate was 12.3, 34.8, and 15.7 per 1,000 live births for white, black, and
      Hispanic women, respectively. There was virtually no overlap in the white and
      black distributions. The variation in mean risk across cities was three times
      greater for black women compared with white women. The threefold disparity in
      mean rate, and two- to threefold increased variation as indicated by standard
      deviation, was maintained in all subanalyses. CONCLUSION: Compared with white
      women, black women have three times the mean VPT birth risk, as well as three
      times the variance in city-level rates. The racial disparity in VPT birth rates
      was composed of characteristics that were constant across MSAs, as well as
      factors that varied by MSA. The increased sensitivity to place for black women
      was unexplained by measured maternal and metropolitan factors. Understanding
      determinants of differences in both the mean risk and the variation of risk among
      black and white women may contribute to reducing the disparity in risk between
      races.

PMID- 18828413
TI  - Prenatal smoking prevalence ascertained from two population-based data sources:
      birth certificates and PRAMS questionnaires, 2004.
AB  - OBJECTIVES: This study provided a population-based estimate of the prevalence of
      smoking during pregnancy by combining information from two data sources: birth
      certificates (BCs) and a self-administered questionnaire. METHODS: We analyzed
      data from 39,345 women who delivered live births in one of 24 states and
      responded to a questionnaire from the Pregnancy Risk Assessment Monitoring System
      (PRAMS), an ongoing, state- and population-based surveillance system. We compared
      prevalence of smoking during pregnancy based on the BC, the PRAMS questionnaire,
      and the two data sources combined. Data were weighted to represent all women
      delivering live births in each of the 24 states during 2004. RESULTS: The
      combined estimate indicated that 15.1% of women reported smoking during
      pregnancy, whereas the BCs alone reported 10.4% and the PRAMS questionnaires
      alone reported 13.4%. CONCLUSIONS: Based on the combined BC and PRAMS
      questionnaire data, the number of infants exposed to tobacco in-utero may be 31%
      higher than is currently reported on the BCs. Combining the data from the two
      different sources led to higher ascertainment of prenatal smoking.

PMID- 18828414
TI  - Degrading and non-degrading sex in popular music: a content analysis.
AB  - OBJECTIVES: Those exposed to more degrading sexual references in popular music
      are more likely to initiate intercourse at a younger age. The purpose of this
      study was to perform a content analysis of contemporary popular music with
      particular attention paid to the prevalence of degrading and non-degrading sexual
      references. We also aimed to determine if sexual references of each subtype were
      associated with other song characteristics and/or content. METHODS: We used
      Billboard magazine to identify the top popular songs in 2005. Two independent
      coders each analyzed all of these songs (n = 279) for degrading and non-degrading
      sexual references. As measured with Cohen's kappa scores, inter-rater agreement
      on degrading vs. non-degrading sex was substantial. Mentions of substance use,
      violence, and weapon carrying were also coded. RESULTS: Of the 279 songs
      identified, 103 (36.9%) contained references to sexual activity. Songs with
      references to degrading sex were more common than songs with references to non
      degrading sex (67 [65.0%] vs. 36 [35.0%], p < 0.001). Songs with degrading sex
      were most commonly Rap (64.2%), whereas songs with non-degrading sex were most
      likely Country (44.5%) or Rhythm & Blues/Hip-Hop (27.8%). Compared with songs
      that had no mention of sexual activity, songs with degrading sex were more likely
      to contain references to substance use, violence, and weapon carrying. Songs with
      non-degrading sex were no more likely to mention these other risk behaviors.
      CONCLUSIONS: References to sexual activity are common in popular music, and
      degrading sexual references are more prevalent than non-degrading references.
      References to degrading sex also frequently appear with references to other risky
      behaviors.

PMID- 18828415
TI  - Condom use among high-risk adolescents: anticipation of partner disapproval and
      less pleasure associated with not using condoms.
AB  - OBJECTIVE: We determined the association of demographic, psychosocial, and
      contextual factors with condom use among a large community sample of at-risk
      adolescents recruited from four locations in the U.S. METHODS: We enrolled 1,410
      adolescents/young adults between the ages of 15 and 21 with a history of
      unprotected sex in the past 90 days at four study sites. Subjects completed an
      audio-assisted, computerized assessment that gathered information about sexual
      behavior and its contexts, substance use, and relevant risk and protective
      attitudes. RESULTS: Nearly two-thirds of adolescents did not use condoms at the
      time of last intercourse and adolescents reported a mean of 15.5 (median = 5)
      unprotected intercourse occasions in the past 90 days. Controlling for relevant
      demographic variables, not using condoms was associated with the perception that
      condoms reduce sexual pleasure, the perception that partners will not approve of
      condom use, and less discussion with partners about condoms. CONCLUSIONS: Even
      across racial/ethnic groups, gender, and geographic locations, several important
      correlates of adolescents' sexual risk reduction were identified. Many
      adolescents may feel that condoms reduce their sexual pleasure and fear partner
      reactions if they initiate condom use. These attitudes may be malleable through
      clinical and community-based interventions.

PMID- 18828416
TI  - Patient risks, outcomes, and costs of voluntary HIV testing at five testing sites
      within a medical center.
AB  - OBJECTIVES: The Centers for Disease Control and Prevention (CDC) recommends
      offering human immunodeficiency virus (HIV) testing to all patients in all high
      HIV-prevalence clinical settings. We evaluated programmatic aspects of HIV
      testing across multiple clinical settings within a single medical center.
      METHODS: We analyzed programmatic data of HIV testing in the Urgent Care Center
      (UCC), inpatient floors, outpatient primary care, a non-clinical Drop-In Center,
      and Emergency Department (ED). HIV testing was by oral mucosal transudate, venous
      blood samples, or rapid testing fingersticks, with Western blot confirmation. We
      compared the sociodemographics and behavioral risks of individuals undergoing HIV
      testing across the five sites and estimated costs per person tested and per HIV
      positive test result. RESULTS: From 2002 to 2004, 16,750 HIV tests were
      conducted, with 229 (1.4%) previously unreported HIV infections diagnosed among
      16,696 valid test results. HIV-positive prevalence was 1.5% for the UCC, 1.5% at
      the Drop-In Center, 1.4% for primary care, 1.2% for inpatient, and 0.6% in the
      ED. Behavioral risks were most prevalent in the UCC and the Drop-In Center. The
      cost per test was lowest in the UCC and highest in the Drop-In Center. The cost
      per previously unreported HIV infection was lowest in the UCC ($1,980) and
      highest in the ED ($9,724). CONCLUSIONS: Although a significant number of HIV
      infections were identified, the number of tests performed represents < 10% of all
      clinical visits. Due to personnel and time constraints, offering HIV testing to
      patients hierarchically in some settings of a high-volume medical center merits
      evaluation.

PMID- 18828417
TI  - Risk factor redistribution of the national HIV/AIDS surveillance data: an
      alternative approach.
AB  - OBJECTIVE: The purpose of this study was to assess an alternative statistical
      approach-multiple imputation-to risk factor redistribution in the national human
      immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS)
      surveillance system as a way to adjust for missing risk factor information.
      METHODS: We used an approximate model incorporating random variation to impute
      values for missing risk factors for HIV and AIDS cases diagnosed from 2000 to
      2004. The process was repeated M times to generate M datasets. We combined
      results from the datasets to compute an overall multiple imputation estimate and
      standard error (SE), and then compared results from multiple imputation and from
      risk factor redistribution. Variables in the imputation models were age at
      diagnosis, race/ethnicity, type of facility where diagnosis was made, region of
      residence, national origin, CD-4 T-lymphocyte cell count within six months of
      diagnosis, and reporting year. RESULTS: In HIV data, male-to-male sexual contact
      accounted for 67.3% of cases by risk factor redistribution and 70.4% (SE = 0.45)
      by multiple imputation. Also among males, injection drug use (IDU) accounted for
      11.6% and 10.8% (SE = 0.34), and high-risk heterosexual contact for 15.1% and
      13.0% (SE = 0.34) by risk factor redistribution and multiple imputation,
      respectively. Among females, IDU accounted for 18.2% and 17.9% (SE = 0.61), and
      high-risk heterosexual contact for 80.8% and 80.9% (SE = 0.63) by risk factor
      redistribution and multiple imputation, respectively. CONCLUSIONS: Because
      multiple imputation produces less biased subgroup estimates and offers
      objectivity and a semiautomated approach, we suggest consideration of its use in
      adjusting for missing risk factor information.

PMID- 18828418
TI  - Using diagnostic codes to screen for intimate partner violence in Oregon
      emergency departments and hospitals.
AB  - OBJECTIVES: Many of the 2.5 million Americans assaulted annually by intimate
      partners seek medical care. This project evaluated diagnostic codes indicative of
      intimate partner violence (IPV) in Oregon hospital and emergency department (ED)
      records to determine predictive value positive (PVP), sensitivity, and usefulness
      in routine surveillance. Statewide incidence of care for IPV was calculated and
      victims and episodes characterized. METHODS: The study was a review of medical
      records assigned > or = 1 diagnostic codes thought predictive of IPV. Sensitivity
      was estimated by comparing the number of confirmed victims identified with the
      number predicted by statewide telephone survey. Patients were aged > or = 12
      years, treated in any of 58 EDs or hospitals in Oregon during 2000, and
      discharged with one of three primary or 12 provisional codes suggestive of IPV.
      Outcome measures were number of victims detected, PPV and sensitivity of codes
      for detection of IPV, and description of victims. RESULTS: Of 58 hospitals, 52
      (90%) provided records. Case finding using primary codes identified 639 victims,
      23% of all estimated female victims seen in EDs or hospitalized statewide. PVP
      was 94% (639/677). Provisional codes increased sensitivity (51%) but reduced PVP
      (50%). Highest incidence occurred in women aged 20-39 years, and those who were
      black. Hospitalizations were highest among women aged > or = 50 years, black
      people, or those with comorbid illness. CONCLUSIONS: Three diagnostic codes used
      for case finding detect approximately one-quarter of ED- and hospital-treated
      victims, complement surveys, and facilitate description of injured victims.

PMID- 18828419
TI  - Public dental expenditures and dental visits among children in the U.S., 1996
      2004.
AB  - OBJECTIVES: Congress created the State Children's Health Insurance Program
      (SCHIP) in 1997 as an expansion of the Medicaid program to provide health
      insurance to children whose family income is above the Medicaid eligibility
      standards-generally up to 200% of the federal poverty level (FPL). This article
      examines changes in the utilization of dental services during a period of
      increasing public funding of dental services. METHODS: Public dental expenditure
      estimates came from the Centers for Medicare & Medicaid Services (CMS), and a
      breakdown of these expenditures by patient age and income level was based on the
      Medical Expenditure Panel Survey (MEPS). RESULTS: According to CMS, funding for
      dental SCHIP and dental SCHIP expansion grew from $0 prior to 1998 to $517
      million in 2004. According to the MEPS, between 1996 and 2004 there was an
      increase in the number and percent of children 2 to 20 years of age who reported
      a dental visit during the past year. These increases were most notable among
      children in the 100% to 200% FPL category. Approximately 900,000 more children in
      this income group visited a dentist in 2003-2004 than in 1996-1997. Children in
      this income group reported an increase in the amount of mean dental charges paid
      for by Medicaid and a real increase in mean dental charges per patient from $217
      to $310. CONCLUSIONS: Recent increases in the public funding of dental services
      targeted to children in the 100% to 200% FPL category were related to increased
      utilization of dental services among these children from 1996 to 2004.

PMID- 18828420
TI  - Assessment of a media campaign and related crisis help line following Hurricane
      Katrina.
AB  - OBJECTIVES: We evaluated the impact of a media campaign targeting stress and
      depression following Hurricane Katrina. We specifically examined public response
      to the campaign's recommendation that people could contact a telephone help line
      for further assistance if needed. METHODS: Call data from Via Link allowed us to
      track trends in 800-number Crisis Line call volume (n = 29,659), which is the
      number recommended in the media campaign, and 2-1-1 Information and Referral Line
      call volume (n = 8,035), which is employed in a control-like manner. With data
      from April 1, 2006, through November 30, 2006, multivariate analysis was used to
      assess trends and differences among and within pre-intervention, intervention,
      and post-intervention. RESULTS: Information and Referral Line call volume, which
      was unrelated to the campaign, did not change over time. In contrast, Crisis Line
      call volume, which was related to the campaign, increased significantly from pre
      intervention to intervention, but not from intervention to post-intervention.
      Furthermore, the daily rate of Crisis Line call volume was constant during pre
      intervention, increased during intervention, but decreased during post
      intervention. CONCLUSION: There is support for the media campaign's influence on
      public behavior to contact Via Link in regard to stress and depression following
      Hurricane Katrina. Analysis helps undermine alternative explanations, including
      general trends in help line call volume and those specific to Crisis Line call
      volume.

PMID- 18828421
TI  - A multiagency effort to reduce bicyclist fatalities and serious injuries in New
      York City.

PMID- 18828422
TI  - The main challenges of Polish oncology.

PMID- 18828423
TI  - When worlds collide: public health and union rights in Virginia Mason Hospital v
      Washington State Nurses Association.

PMID- 18828424
TI  - Filling the gap: providing formal training for epidemiologists through a graduate
      level online certificate in field epidemiology.

PMID- 18828425
TI  - Teaching emergency preparedness to public health workers: use of blended learning
      in web-based training.

PMID- 18828426
TI  - Plasticity of myenteric neurons.
AB  - The nervous system exerts a profound influence on all digestive processes. The
      wall of digestive system is endowed with its own, local nervous system referred
      to as the enteric or intrinsic nervous system which is responsible for the
      modulation of the rhythmic gastrointestinal peristaltic activities along with
      other functions. The principal components of the enteric nervous system are two
      neuronal networks: myenteric and submucosal, embedded in the wall of the
      digestive tract and extend from esophagus to anus. The musculature of different
      parts of gastrointestinal tract is differently disposed to perform different
      functions. Thus the aim of present study was to demonstrate the presence of
      neurons and to quantify the number of collections of neurons, number of neurons
      in each collection and area of the neurons of the plexus. One cm piece from all
      the parts of GIT containing entire wall was taken from the same region of 5 adult
      cadavers of postmortem cases which were embalmed in the Department ofAnatomy,
      Postgraduate Institute of Medical Sciences and Research, Chandigarh and were
      processed for paraffin sectioning. 5 and 10 micro thick serial sections were
      obtained and 6th and 7th slides were stained with: Hematoxylin and Eosin and
      Marsland, Glees and Erikson's silver stain. The slides were photomicrographed
      using digital camera. The morphometrical analysis was done using Image Pro
      Express software. Aggregations of 1-31 neurons present in myenteric network
      located between longitudinal and circular muscle layers of the GIT whose size
      varied from 10.263-259.660 microm2. They were oval or round; multipolar, arranged
      in two rows and dispersed in groups in connective tissue of muscularis propria.
      The collections of neurons were appeared to be more numerous in appendix and
      ileoceacal valve.

PMID- 18828427
TI  - Histological pattern of ovarian tumors and their age distribution.
AB  - A female's risk at birth of having ovarian tumor sometime in her life is 6-7%.
      Relative frequency of ovarian tumor is different for western and Asian countries.
      Two third of ovarian tumors occur in women of reproductive age group. This study
      was done in Tribhuvan University Teaching Hospital with aim to find out frequency
      of different histological types of ovarian tumors and their age distribution and
      thus provide an institutional experience from Nepal also. One hundred and sixty
      one ovarian tumors, reported from April 2004 to March 2006 were included in the
      study. One hundred and thirty five of these tumors (83.9%) were benign and 16.1%
      (26/161) were malignant. Surface epithelial tumors were most common (52.2%)
      followed by germ cell tumors (42.2%). Mature cystic teratoma was commonest benign
      tumor (48.2%). Serous adenocarcinoma was commonest malignant tumor (46.2%). For
      all age groups, benign tumors were more common than malignant ones. Most ovarian
      tumors (47.2%) were seen between 21 -40 years where as most malignant tumors
      (73.1%) were seen above 40 years. In 1st two decades, germ cell tumors were more
      common than other tumors.

PMID- 18828428
TI  - Causative agents of urinary tract infections in children and their antibiotic
      sensitivity pattern: a hospital based study.
AB  - A retrospective study was conducted to find out the causative agents of urinary
      tract infection (UTI) in children and their antibiotic sensitivity pattern among
      Nepalese children. This was done at Kanti Children's Hospital in Kathmandu
      (Nepal) by analyzing the records of urine samples collected for culture and
      sensitivity tests over a period of six months (April to November, 2007). Of the
      total 1878 mid-stream urine samples collected from suspected cases of UTI, 538
      (28.6%) were positive for pathogenic organisms. There was no significant
      difference in growth positive rate in two genders (M: 51.7% and F: 48.3%). Of the
      various pathogenic organisms isolated, Escherichia coli constituted for 93.3%
      followed by Proteus sp, Klebsiella sp, Citrobacter sp, Staphylococcus aureus and
      others. E. coli was found to be most sensitive to amikacin, chloramphenicol,
      nitrofurantoin and ofloxacin and least sensitive to most commonly used drugs like
      cephalexin, nalidixic acid, cotrimoxazole and norfloxacin.

PMID- 18828429
TI  - Prevalence of antimicrobial chemotherapy in hospitalized patients in the
      department of internal medicine in a tertiary care center.
AB  - Use of antimicrobial agents (AMAs) is associated with significant reduction in
      morbidity and mortality. However, indiscriminate and injudicious use of AMAs
      leads to the ineffective treatment, increased adverse effects, exacerbation or
      prolongation of illness, emergence of bacterial resistance and an additional
      burden of an expensive medical cost to the patients. So controlled use of AMAs at
      right dose, right interval and right duration is of utmost importance. In this
      retrospective study, prevalence and prescription patterns, and cost of the
      prescribed AMAs in the hospitalized patients in the department of internal
      medicine in a tertiary care center were analyzed. A total of 428 hospitalized
      patients were included in the study. Out of 428 patients, 274 (64.0%, P < 0.01)
      patients received AMAs for therapeutic (66.4%) and prophylactic (24.1%) purposes.
      In 9.5% patients AMA prescription was inappropriate. Use of intravenous route was
      significantly higher (55.48, P < 0.01) than the oral route. COPD with acute
      exacerbation was most frequent condition for AMA prescription. Majority (90.42%)
      of AMA prescriptions were based on empirical basis. Mean number of AMA per
      patient was 2.12 (minimum 1 and maximum 8). Most frequently prescribed AMA was
      Ceftriaxone (30.2%) from cephalosporin group (33.9%, P < 0.05). Patients received
      AMAs for the duration of 1-31 days and total cost of single AMA dosage regimen
      was as high as $ 482.3. As most of the hospitalized patients were prescribed AMA
      empirically, strategic AMA prescription guidelines and AMA prescription
      monitoring systems are extremely necessary in the hospitals to prevent emergence
      of microbial resistance and to expedite the cost effectiveness of medical
      treatment.

PMID- 18828430
TI  - Tuberculosis co-infection in HIV infected persons of Kathmandu.
AB  - Tuberculosis is itself a major Public health problem in Nepal and the emergence
      HIV further complicated the issue. A cross-sectional analytical study was
      conducted between January 2004 and August 2005, with a general objective to
      determine the Tuberculosis co-infection status in HIV/AIDS cases of Nepal.
      Altogether 100 HIV infected persons visiting different Voluntary counseling and
      testing centers (VCT) and HIV/AIDS care centers located in Kathmandu valley were
      enrolled in the study. Investigation of tuberculosis was done by standard method
      prescribed by WHO using sputum specimen. Among 100 HIV infected cases, 66 (66.0%)
      were males and 34 (34.0%) were females. Majority of the HIV cases were in the age
      group 21-30 (60.0%) followed by 31-40 (31.0%). Tuberculosis was detected in 23
      cases with highest prevalence in the age group 21-30 years (65.2%). No
      significant relationship could be established between gender and TB (c2 = 0.83, p
      > 0.01).Significant relationship was established between smoking/alcoholic habit
      and the subsequent development of tuberculosis (c2 = 7.24, p < 0.05 for smoking
      habit; c2 = 4.39, p < 0.05 for alcoholic habit at 1 degree of freedom). Among 22
      culture positive isolates the predominant was Mycobacterium avium complex (40.9%)
      followed by M. tuberculosis (27.3%), M. kansasii (18.2%), M. fortuitum (9.1%) and
      M. chelonae (4.5%). Among the 23 cases of tuberculosis, 22 cases were diagnosed
      by cultural technique of which 4 cases were smear positive while the remaining
      one case was diagnosed by direct microscopy although it was culture negative.
      Smear negative Tuberculosis is found to be alarmingly higher in HIV positive
      individuals of productive age group. The disease significantly higher in smokers
      and alcoholics.

PMID- 18828431
TI  - Intestinal parasitosis among subjects undergoing cataract surgery at the eye
      camps in rural hilly areas of Nepal.
AB  - Present study investigated the intestinal parasitosis among 221 subjects
      undergoing cataract surgery (M: 129 and F: 92; aged 13-86 years) at the eye camps
      in three rural hilly districts (Ramechhap, Sindhupalchok and Dhading) in 2006.
      Stool samples collected in clean, dry, screw capped plastic containers were
      examined locally by direct smear technique and anti-parasitic drugs were
      distributed to parasite positive subjects. The remaining stool samples were fixed
      with 10% formal-saline, transported to Shi-Gan Health Foundation/Nat'l Inst of
      Trop Med and Public Health Research, Kathmandu and re-examined by formal-ether
      sedimentation technique. A total of 148 samples (66.9%) were positive for some
      kind of intestinal parasites (F: 68.5% and M: 65.9%; P > 0.05). Ramechhap
      (Manthali) and Sindhupalchok (Chautara) had higher positive rate (71.8% and
      70.7%, respectively) than in Dhading (Salyantar) (60.0%) (P > 0.05). Tibeto
      Burman (indigenous nationalities) ethnic group had highest positive rate (70.1%)
      compared with Indo-Aryan (64.7%) and Dalits (57.7%). Subjects without toilet
      (latrine) had marginally higher positive rate (69.7%) than those having toilet at
      their home (65.5) (P> 0 .05). Age was independent of positive rate. Vegetarians
      had marginally higher parasitic infection rate compared to their non-vegetarian
      counterparts. Helminths were more common than protozoa. Overall, hookworm was the
      commonest parasite detected. However, Ascaris was common in Dhading District.
      Entamoeba histolytica was most common among protozoa and was followed by
      Cyclospora and others.

PMID- 18828432
TI  - Correlation of prostate volume with international prostate symptom score and
      quality of life in men with benign prostatic hyperplasia.
AB  - The aim of this study was to correlate the prostate volume with international
      prostate symptom score (IPSS) and quality of life (QOL). Hundred consecutive
      patients diagnosed as having benign prostatic hyperplasia were included. All
      patients were interviewed using standardized questionnaires for International
      Prostate Symptom Score, which include one single disease-specific quality of life
      question. Transabdominal ultrasonogram was used to assess the prostatic volume.
      Data was analyzed using the statistical package for social sciences (SPSS) for
      Windows. The mean age and median duration of symptom was 67.5 years and 12.0
      months respectively. The mean volume of prostate was 42.5 cm3. Most of the
      patients had severe symptoms with mean IPSS of 23.5 and single disease-specific
      QOL score of 5.2. The correlation between the prostate volume and age, IPSS, and
      QOL score were not statistically significant except for two domains; incomplete
      emptying and nocturia that appear to be correlated with prostate volume. The
      correlation between IPSS and QOL score was strong. Similarly, correlation between
      QOL score and age was significant but weak. In conclusion, prostate volume had no
      correlation with age, symptom score, and quality of life score. So prostatic size
      should not be an only and important consideration; moreover, we should assess the
      impact of symptoms while treating the cases.

PMID- 18828433
TI  - Cytological diagnosis of bancroftian filariasis in lesions clinically anticipated
      as neoplastic.
AB  - Filariasis is a common disabling parasitic disease in this region and cytological
      diagnosis is often not required. Cytology has important role in diagnosis of sub
      clinical filariasis. Most cases of cytologically diagnosed filariasis are
      clinically unanticipated. Microfilaria, ova and fragments of adult worm of
      Wuchereria bancrofti, in exfoliative as well as aspiration cytology have been
      reported and are useful in cytological detection of bancroftian filariasis.
      Microfilaria is frequently detected in association with neoplasm, although the
      role in tumorogenesis is controversial. The objective of the study was to
      investigate importance of cytology in diagnosis of filariasis in lesions
      clinically anticipated to be of neoplastic and to review the cytomorphology of
      bancroftian filaria and its association with neoplasm. This is a retrospective
      study carried out in cytology department of Tribhuvan University Teaching
      Hospital. 14 cases of cytological specimen out of 4291 (0.3%) showed
      microfilaria; 12 cases were from FNAC from different sites and 2 cases were from
      pleural fluid. 2 cases showed ova in addition to microfilaria and one of them in
      addition showed fragment of adult worm. Microfilaria in 4 cases of FNAC and one
      case ofpleural fluid were associated with malignant cells.

PMID- 18828434
TI  - Fixation of extra articular distal radial fractures with non bridging external
      fixator.
AB  - Severely comminuted fractures of distal radius often lead to impairment of wrist
      function. A prospective study was performed on 30 patients aged between 35-65
      years of extra-articular fractures of distal radius. All patients were treated
      with closed manipulation of the fracture an application of non-bridging (radio
      radial) external fixator under radiological control. At six months after the
      injury functional results were good with near normal movements of the wrist and
      hand. Radiological fracture alignment was satisfactory with no significant
      shortening of the radius. There were no re-displacements and none of the patients
      required a second operation. Superficial pin site infection occurred in two
      patients without pin loosening. We recommend non bridging external fixator as a
      good method of treatment of extra articular fractures of the distal radius in
      younger patients.

PMID- 18828435
TI  - Ambulatory blood pressure monitoring: a useful tool to diagnose hypertension and
      supervise it's treatment.
AB  - Automatic ambulatory blood pressure monitoring (ABPM) for the diagnosis and
      treatment ofhypertension(HTN) is not common in Nepal. The purpose of this study
      is to evaluate various characteristics of hypertensive patients undergoing ABPM
      before starting antihypertensive treatment and evaluate the adequacy of the blood
      pressure (BP) control during antihypertensive treatment. ABPM was performed in
      108 consecutive patients attending the hypertension clinic of Nepal Medical
      College Teaching Hospital from 1st March 2005 to 30th April 2007 with DynaPulse
      5000A (version 3.20q ) for approximately 24 hours. Male female ratio was 59:49
      and age (mean +/- SD) was 47.8 +/- 16.4 years. The maximum use of ABPM (25.9%)
      was noted in the age group of 40-49 years. Body mass index was 25.7 +/- 3.8.
      Diabetes was noted in 13% patients. Maximum use of ABPM was observed in Newar
      ethnic group (56.5%). ABPM was used for the diagnosis of HTN in 62.0% patients
      and for follow up in 38.0% patients. Severe HTN was seen in approximately half
      (47.2%) of the hypertensive patients. Majority of the patients (88.0%) had dipper
      type of HTN. Beta-blocker (35.6%), ACE inhibitor/Losartan (31.1%) and calcium
      channel antagonist (26.7%) were the usual antihypertensive agents used. Single
      antihypertensive agent was used in the majority of patients (64.1%). In a small
      number of patients (42, 38.9%) undergoing ABPM during antihypertensive therapy,
      the adequacy of control of HTN was very poor.

PMID- 18828436
TI  - Mini-open reduction and intramedullary interlocking nailing of fracture shaft of
      tibia without an image intensifier.
AB  - Intramedullary interlocking tibial nailing is usually performed using an image
      intensifier. But being expensive, it is not available in the most of the
      hospitals of resource-poor countries of the world. The purpose of this study is
      to analyze the results of interlocking nailing without the use of an image
      intensifier. This is the retrospective study of 55 diaphyseal tibial fractures
      treated with minimally open reduction and internal fixation with interlocked
      intramedullary nail fixation. The proximal locking of the nail with the screws
      was made using external jig and for the distal locking direct visualization of
      the hole was carried out. There were 15 females and 40 males. The average age in
      years was 32 with a range of 18 to 64 years. The surgical approach was medial
      parapatellar. The average follow up period was 4 months. This period ranged from
      3 months to 14 months. The union time in an average was 4 months. The
      complication mainly was distal screw loosening leading to valgus deformity and
      shortening in 1 case. It is, therefore, concluded that interlocking
      intramedullary nailing can be performed with proximal and distal locking
      accurately without the use of an image intensifier.

PMID- 18828437
TI  - Hisopathological spectrum of glomerular disease in nepal: a seven-year
      retrospective study.
AB  - We analyzed 137 cases of renal biopsies at the Department of Pathology from 2001
      to 2007. The average age was 30.6 years (range, 13-72) for males and 32.9 years
      (range, 11-75) for females. The male to female ratio was 1.6: 1. The most common
      clinical syndromes for performing renal biopsy were nephrotic syndrome (81.6%)
      followed by asymptomatic urinary abnormalities (5.8%), nephritic syndrome (3.6%),
      hypertension (2.9%), chronic kidney disease (2.2%), acute renal failure (2.2%),
      cirrhosis (0.7%) and transplant rejection (0.7%). The major glomerular diseases
      in descending order of frequency were membranous glomerulonephritis (MGN; 42.3%),
      membranoproliferative glomerulonephritis (MPGN; 21.9%), minimal change disease
      (MCD; 10.2%), focal segmental glomerulosclerosis (FSGS; 8.0%), IgA nephropathy
      (2.9%), post infectious glomerulonephritis (GN) (2.2%), chronic GN (2.2%),
      tubulointerstitial nephritis (TIN; 1.5%), lupus nephritis (1.5%), focal
      proliferative GN (1.5%), Clq nephropathy (1.5%), amyloidosis (1.5%) and other
      minor form of glomerular diseases (2.8%). The pattern ofglomerulonephritis in our
      study is different from the reports of other developing countries. It could be
      due to various races and altered environmental condition. The information
      obtained from these results can be used as baseline data for making efficient
      research in Nepalese population in the future. The higher frequency of MGN and
      MPGN among Nepalese in comparison with other developing countries deserves
      further evaluation.

PMID- 18828438
TI  - Evaluation of different tests for detection of Staphylococcus aureus using
      coagulase (coa) gene PCR as the gold standard.
AB  - A total of 288 staphylococcal specimens isolated from different clinical
      specimens were selected for the evaluation of tests used to detect Staphylococcus
      aureus. The coagulase (coa) gene PCR was preformed, which confirmed 288 specimens
      as S. aureus and 51 specimens as coagulase negative staphylococci (CONS). All the
      specimens were subjected to slide coagulase test, Slidex Staph plus test and tube
      coagulase test. Sensitivity, specificity, positive predictive value and negative
      predictive values of were calculated using coa gene PCR as gold standard for the
      detection ofS. aureus. The tube coagulase test showed very good sensitivity
      (98.7%), specificity (98.1%), PPV (99.5%) and NPV (94.4%) than other methods.
      Slidex Staph plus test showed fairly good sensitivity and specificity. Slide
      coagulase test has good specificity but poor sensitivity. Therefore we recommend
      that tube coagulase test be done routinely for the detection ofS. aureus in
      microbiology laboratory.

PMID- 18828439
TI  - Acute renal failure in Nepal Medical College Teaching Hospital.
AB  - Total 45 patients (male 27 and female 18) of acute renal failure (ARF) admitted
      in Nepal Medical College Teaching Hospital over a period of 12 months (1st of
      Baisakh 2064 BS to 31st of Chaitra 2064 BS) were enrolled in the study. Sixty
      four percent of study population were of age group 21-60 years. Acute
      Gastroenteritis 33, sepsis 5, hemorrhage 2, others 5 were the different causes of
      ARF. Serum creatinine of the study population before and after treatment was 4.35
      +/- 2.72 and 1.38 +/- 0.72 mg/dl respectively. Similarly serum urea before and
      after treatment was 101.78 +/- 57.56 and 42.60 +/- 30.46 mg/dl respectively.
      Thirty three patients were managed by non dialytic modality of therapy and 12
      patients needed hemodialysis. Blood urea of those patients who underwent
      nondialytic therapy was significantly less than of those who underwent
      hemodialysis (80.65 +/- 38.21 vs. 151.08 +/- 66.22; p = 0.004). Serum creatinine
      was also significantly lower in nondialytic therapy group (3.15 +/- 1.15 vs. 7.64
      +/- 3.10; p = 0.000) ARF patients with very high urea, creatinine and disturbed
      electrolytes required dialysis. Average session of hemodialysis was 3.4. Thirty
      five patients were cured, 6 left against medical advice, 3 were discharged on
      request, and one patient of sepsis expired during the course of treatment. Acute
      gastroenteritis was the leading cause of ARF and outcome was excellent even
      without dialysis in most of the cases provided the treatment was started early
      and appropriately.

PMID- 18828440
TI  - Simultaneous occurrence of hematometrocolpos and consecutive pregnancies in
      uterine didelphys : a case report.
AB  - Hematometrocolpos drained abdominally at laparotomy done, with suspicion of an
      ovarian torsion in an adolescent with ipsilateral renal agenesis, was eventually
      rediscovered to have in coexistent uterine didelphys in a 25 year P3+0 at the
      time repeat caesrean for breech in the event of third parturition, complicated by
      partum hemorrhage as in all her previous delivery (first vaginal delivery and
      retained placenta, second caesarean for obstructed labor by non pregnant half of
      didelphic uterus). This illustrates how simultaneous occurrence of
      hematometrocolpos can go unnoticed although there was every reason for this
      condition not to go unrecognized for the simple fact ofhemivaginal obstruction
      and hematometra with ipsilateral renal agenesis (on the left side) unaffecting
      the consecutive pregnancy in the other uterus.

PMID- 18828441
TI  - Spontaneous extrusion of subconjunctival cysticercous cyst: a case report.
AB  - Ocular cystericosis is the common occurrence among the people of lower
      socioeconomic status and poor personal hygiene in developing countries. However,
      spontaneous extrusion of subconjuctival cysticercous cyst is a rare incidence.
      The present case report describes a spontaneous extrusion of subconjunctival cyst
      in a 12 year old boy in our clinical set-up. The histopathological examination
      revealed subconjunctival cysticercous cyst. The extrusion was associated with
      improvement in clinical sign and symptoms. Cysticercosis should be considered in
      any case of inflammatory swelling of subconjunctival space especially in people
      of lower socioeconomic status and poor personal hygiene.

PMID- 18828442
TI  - Rare causes of voice hoarseness: a case report.
AB  - We report two contrasting and rare cases of voice hoarseness in young patients of
      tubercular aetiology. First case report is of isolated tubercular recurrent
      laryngeal nerve palsy in a patient who presented with hoarseness of voice. Chest
      radiograph showed a left hilar prominence and bronchial washings isolated acid
      fast bacilli. Hoarseness of voice as an initial symptom due to isolated vocal
      cord palsy with no morphological lesions in the larynx and without obvious
      parenchymal infiltration often poses a diagnostic dilemma. Second case report
      highlights the possibilities of tuberculosis of the vocal cords mimicking tumour
      of the larynx. This patient had an ulcerative growth involving the vocal cord
      which was initially mistaken for malignancy. Patient also had concomitant miliary
      shadowing in the lungs and laryngoscopic biopsy revealed the growth to be
      tuberculosis. Early diagnosis and intervention with antitubercular treatment is
      vital as it results in complete recovery with reversal of vocal hoarseness.

PMID- 18828443
TI  - Superior mesenteric artery syndrome: case report.
AB  - Superior mesenteric artery (SMA) syndrome is a rare acquired disorder in which
      acute angulation of SMA causes compression of the third part of the duodenum
      between the SMA and the aorta, leading to obstruction. Loss of fatty tissue as a
      result of a variety of debilitating conditions is believed to be the etiologic
      factor causing the acute angulation. We report a case of 30 years old lady who
      presented with postprandial abdominal pain at the epigastric region, colic type
      without radiation accompanied by nausea, postprandial vomiting and weight loss.
      Esophageal gastric series revealed an abrupt interruption in the contrast medium
      flow at the level of the junction of third portion (midpart) of the duodenum in
      barium studies. Adiverticula is noted just proximal to the site of obstruction.
      High resolution ultrasound and color Doppler sonography showed narrowing of the
      aortomesenteric angle to 220. Duodenojejunostomy was performed in the patient.
      Unfortunately the patient later was admitted in the hospital for refractory
      gastroparesis associated with superior mesenteric artery syndrome. Although open
      and laparoscopic duodenojejunostomy have been described as the best surgical
      treatment options for Wilkie's syndrome, but further attention is needed to the
      management of patients with refractory symptoms of gastroparesis after corrective
      surgery.

PMID- 18828444
TI  - The history of modern Nepalese medicine.

PMID- 18828445
TI  - Expression of alpha-hemoglobin stabilizing protein and cellular prion protein in
      a subclone of murine erythroleukemia cell line MEL.
AB  - Alpha-Hemoglobin stabilizing protein (AHSP) functions as the erythroid-specific
      molecular chaperon for alpha-globin. AHSP gene expression has been reported to be
      downregulated in hematopoietic tissues of animals suffering from prion diseases
      though the mechanism remains to be clarified. Herein, we demonstrate that
      MELhipod8 cells, a subclone of murine erythroleukemia (MEL) cells, have prion
      protein (PrPc) on the cell surface and have highly inducible expression of the
      AHSP and alpha- and beta-globin genes, resembling the expression pattern of the
      PrP and AHSP genes in bipotential erythroid- and megakaryocyte-lineage cells
      followed by erythroid differentiation in normal erythropoiesis. Moreover,
      MELhipod8 cells exhibit greater effective erythroid differentiation with a
      population of hemoglobinized normoblast-like cells than that observed for the
      parental MEL cells. These findings suggest that MELhipod8 cells could provide a
      mechanism for downregulation of the AHSP gene in prion diseases.

PMID- 18828446
TI  - Effects of anti-tick cocktail vaccine against Rhipicephalus appendiculatus.
AB  - Rhipicephalus appendiculatus serpin-3 (RAS-3), R. appendiculatus serpin-4 (RAS-4)
      and a 36-kDa immuno-dominant protein of R. appendiculatus (RIM36) were reported
      as candidate antigens for the anti-tick vaccine to control ixodid ticks. In the
      present study, we generated recombinant proteins of RAS-3 (rRAS-3), RAS-4 (rRAS
      4) and RIM36 (rRIM36), and assessed their potency as an anti-tick cocktail
      vaccine in cattle model. RT-PCR analysis showed that RAS-3, RAS-4 and RIM36
      transcripts were detected in both adult male and female ticks during feeding.
      Immunization of cattle with the combination of rRAS-3, rRAS-4 and rRIM36 had
      raised antibodies against all recombinants and anti-sera had reacted with the
      molecules from the tick salivary gland extract. Tick infestation challenge
      demonstrated protective immunity against female ticks, resulting in mortality
      rates of 39.5 and 12.8% for the vaccinated and control groups, respectively.
      Moreover, the mortality rate of Theileria parva-infected female ticks was 48.5
      and 10.8% in the vaccinated and control group, respectively. In order to evaluate
      the levels of pathogen transmission capacity by T. parva-infected ticks fed on
      immunized cattle, the occurrence of T. parva in the bovine parotid lymph node and
      peripheral blood was also determined and quantified by real-time PCR. Although
      the infection with T. parva could not be protected by the vaccine, the occurrence
      of pathogen in peripheral blood was delayed 1 to 2 days after the infestation
      challenge in vaccinated group. These results suggest that this cocktail vaccine
      plays a role in the prevention of tick infestation.

PMID- 18828447
TI  - A BOLD-fMRI study of cerebral activation induced by injection of algesic chemical
      substances into the anesthetized rat forepaw.
AB  - This study was performed to examine whether the brain activities induced by
      noxious algesic chemical substances in anesthetized animals could be detected by
      blood oxygen-level-dependent functional magnetic resonance imaging (BOLD-fMRI).
      Multislice gradient echo images of the primary somatosensory cortex were obtained
      using a 7.05 T superconducting system and a one-turned surface coil centered over
      the primary somatosensory cortex of the 1.0%-isoflurane-anesthetized rat. The Z
      score t-map of BOLD signals and its time-course analysis revealed that
      subcutaneous injection of formalin into the left forepaw immediately induced an
      early response in the contralateral primary sensory cortex lasting for a few
      minutes, followed by a late response until 20 min after stimulation. In contrast,
      injection of capsaicin into the left forepaw evoked only the early response.
      Furthermore, pretreatment with morphine completely abolished these responses
      induced by the chemical algesic substances. Thus BOLD-fMRI is a useful method to
      analyze the brain activities of painful stimulation in anesthetized animals.

PMID- 18828448
TI  - Downregulation of male-specific cytochrome P450 by profenofos.
AB  - The health hazards of individual organophosphorus insecticides have been
      characterized by their acute toxicity, mainly by investigating their
      cholinesterase inhibition. However, the chronic effects of most of these
      toxicants on the drug-metabolizing enzymes have not been investigated. Profenofos
      (O-4-bromo-2-chlorophenyl O-ethyl S-propyl phosphorothioate) is an
      organophosphorus pesticide widely used in cotton cultivation. In the present
      study, we investigated the effect of profenofos on male-specific cytochrome P450
      (CYP) enzymes in adult Wistar rats. We orally administered 17.8 mg/kg body
      weight, twice weekly for 65 days. Profenofos downregulated levels of hepatic and
      testicular CYP2C11 and CYP3A2 mRNA and protein expression. Testicular aromatase
      (CYP19A) mRNA was decreased in the profenofos-treated rats compared to controls.
      Overall, the present study suggests that profenofos acts as an endocrine
      disruptor of male-specific CYP enzymes and affects testosterone concentration,
      which implicates its deleterious effects on animal or human males chronically
      exposed to organophosphorus pesticide.

PMID- 18828449
TI  - Drills and spills.

PMID- 18828450
TI  - Regulation matters.

PMID- 18828451
TI  - The non-technical skills of theatre nurses.
AB  - What are 'non-technical' skills and why would they be relevant to theatre
      practitioners? This is a new area of research for healthcare based on a well
      developed approach from the world of aviation. Non-technical skills are the
      cognitive and social skills that complement technical skills to achieve safe and
      efficient practice in safety-critical occupations. These skills include
      communication, leadership, teamwork, stress management and situation awareness.

PMID- 18828452
TI  - Abortion: implications for theatre staff.
AB  - Abortion is controversial and often sparks polemic debate. Nevertheless, theatre
      staff need to know the different methods of abortion, to be aware of the current
      UK legal position and possible future directions. Theatre staff must be mindful
      of their own ethical and emotional position in order to play a vital role in
      making women attending for this surgery feel at ease during such an emotionally
      charged event.

PMID- 18828453
TI  - Noisiness in operating theatres: nurses' perceptions and potential difficulty
      communicating.
AB  - Elevated operating theatre noise can be hazardous to patient safety and may cause
      occupational stress. In a nine-hospital study, background noise and average noise
      were measured, during operations in different subspecialties, and found to be
      higher than noise levels recommended by the World Health Organization (WHO) for
      hospital areas in which patient care takes place. In operations in which nurses
      had also answered a question about hearing 'quiet', 'normal', and 'loud' talking,
      speech interference levels were estimated and indicated that nurses and other
      personnel had to substantially raise their voices to be well understood.

PMID- 18828454
TI  - Preoperative consent: how to make sure your practice is legal--Part two.
AB  - The Mental Capacity Act 2005 (MCA) came into force in October 2007. This is now
      the keystone of the law regarding the assessment of capacity to consent and the
      treatment of those who lack capacity to consent for themselves. The first article
      in this two-part series (Corfield & Pomeroy 2008) covered preoperative consent:
      this article discusses the MCA (with accompanying relevant case law) in more
      detail by the use of illustrative examples and concentrates on issues that can
      arise once the patient is in the operating suite.

PMID- 18828455
TI  - The safety of medical devices: the tools of your working day.
AB  - You are trained and skilled in the practice of safe clinical procedures. Are you
      aware however that the safety of the medical devices, which includes medical
      equipment, that you use routinely in your clinical working day have been designed
      to be safe for both you and for patients? This is a legal requirement of the
      Medical Device Regulations by which manufacturers of medical devices and medical
      equipment are required to design and manufacture their products. That they
      conform to these regulations is designated by the CE Mark that has to be
      displayed on the product or on its labelling. This article will outline the
      legislative requirements of the regulations with which manufacturers have to
      comply.

PMID- 18828456
TI  - Florence Nightingale: creator of modern nursing and public health pioneer.
AB  - In starting this series of articles on distinguished women in nursing, medicine
      and the related healthcare professions, the choice of the first name is obvious.
      Florence Nightingale is, I suggest, the most famous female in the long history of
      medicine and is a name that is known and revered throughout the world. Most
      people--even those in 'the trade'--think of her as 'the lady with the lamp', the
      heroine who went out to the Crimean War and nursed the sick and wounded at
      Scutari. Important though this was, her main contribution was her continued work,
      long after the war, in nursing organisation and training, hospital planning,
      public and military health and her pioneering work in the efficient gathering of
      medical statistics.

PMID- 18828457
TI  - Constrictive pericarditis. A diagnostic challenge.

PMID- 18828458
TI  - ECG of the month. ECG read as normal in a man with chest burning and an elevated
      serum troponin level. Posterior myocardial infarct.

PMID- 18828459
TI  - Clinical case of the month. Massive pulmonary embolism: a case report and review
      of literature. Pulmonary embolism.

PMID- 18828460
TI  - Radiology case of the month. Pelvic pain in an adult woman. Paget's disease of
      bone.

PMID- 18828461
TI  - Calcified constrictive pericarditis, aortic stenosis, and coronary artery
      disease: diagnosis and treatment solutions for a 78-year-old patient.

PMID- 18828462
TI  - On-pump versus off-pump coronary artery bypass surgery: a comparison of two
      consecutive series.
AB  - BACKGROUND DATA: On-pump and off-pump techniques are both widely used approaches
      to coronary artery bypass surgery. Yet, statistically valid comparisons of the
      results between the two groups have been limited, in part, by patient selection
      bias. METHODS: Two hundred sixty-nine consecutive patients undergoing off-pump
      coronary artery bypass and 379 consecutive patients undergoing on-pump bypass
      were compared in a retrospective chart review. The two groups were compared for
      preoperative characteristics as well as operative outcomes. To avoid selection
      bias, no on-pump coronary artery bypass surgery was performed during the off-pump
      coronary artery bypass series, and no patients were done off-pump during the
      coronary artery bypass series. RESULTS: There was no statistical difference in
      the groups pre-operatively except that there were slightly more patients with
      three-vessel disease in the on-pump group and more patients with single vessel
      disease in the off-pump group. Significant benefits were found in the off-pump
      group in that they required fewer re-operations for bleeding (0.8% vs. 5.7%, p
      value < 0.002), and they left the hospital with higher hematocrits (32.1% vs.
      30.8%, p-value < 0.001). Patients who had off-pump coronary artery bypass also
      had fewer sternal dehiscences (0% vs. 1.8%, p-value < 0.027). More patients
      receiving off-pump bypass demonstrated the need for prolonged mechanical
      ventilation (8.2% vs. 2.5%, p-value < 0.027), and they also had significantly
      fewer grafts (3 vs. 3.2, p-value < 0.005). There was no statistically significant
      difference among the other outcomes investigated. CONCLUSIONS: While there were
      no significant differences in some of the outcomes studied, others showed
      significant advantages in favor of off-pump surgery. Substantial advantages in
      off-pump coronary artery bypass were seen in bleeding reduction, improved sternal
      healing, and higher discharge hematocrits despite fewer transfusions. These
      advantages and others reported in specific high-risk patient groups, combined
      with documented cost reductions, warrant continued use of off-pump techniques.
      Off-pump coronary artery bypass is a safe, proven method with significant
      advantages over on-pump methods and, when appropriate, should be offered to
      patients undergoing coronary bypass surgery.

PMID- 18828463
TI  - Increasing pesticide-resistant ectoparasitic infections may increase pesticide
      poisoning risks in children.
AB  - Head louse and scabies mite infestations are common among pre-school and school
      age children, and topical pesticides are frequently prescribed to treat such
      conditions. Ectoparasite resistance to the safest and most commonly prescribed
      pyrethrin/pyrethroid pesticides for ectoparasitic infections has, however, been
      increasing since the 1980s. The increasing resistance of these arthropods to the
      safest pesticides may lead to greater use of more toxic, alternative pesticides
      to control infestations and to prevent institutional outbreaks. MEDLINE and
      Cochrane searches, 1966-2008, were conducted to assess the impact of increasing
      pesticide resistance on prescribing practices for ectoparasitic infections and to
      describe the evolving global epidemiology of pediatric poisonings by more toxic
      pediculicides and miticides, including carbamates, organochlorines, and
      organophosphates. Pharmacists, physicians, and poison control personnel should be
      fully informed about increasing pesticide resistance among the most commonly
      encountered ectoparasites of children and the institutionalized and be prepared
      to prevent and to treat accidental home and institutional pesticide poisonings
      with more toxic pesticides.

PMID- 18828464
TI  - Management of postoperative chylothorax utilizing percutaneous CT-guided
      drainage.
AB  - This case presentation describes a patient who developed postoperative
      chylothorax after transhiatal esophagectomy for achalasia that was successfully
      managed by percutaneous drainage. A review of chylothorax causes and treatment
      options are presented. The effectiveness of percutaneous drainage for treatment
      of chylothorax is discussed. This minimally invasive method is a valuable
      alternative to open surgical or thoracoscopic drainage.

PMID- 18828465
TI  - The influence of Dr. John Adriani on the American Board of Anesthesiology Oral
      Examination.
AB  - Though Dr. John Adriani was respected worldwide for his contributions in the
      clinical arena, he has received little acknowledgement for his influence on the
      American Board of Anesthesiology (ABA) oral exam. His essay, "The oral
      examination of the American Board of Anesthesiology" was the first work of its
      kind helping new and experienced examiners approach the examination process. An
      analysis of the literature investigating the reliability of the ABA oral exam
      from before and after the release of Dr. Adriani's document reveals that Dr.
      Adriani's suggestions likely helped improve the examination process.

PMID- 18828466
TI  - Landmark legislation reflects important lessons learned from Hurricane Katrina.

PMID- 18828467
TI  - What have we done for you lately? Medicare cuts avoided--it's OK to celebrate!

PMID- 18828468
TI  - AMS: Medical home and primary care.

PMID- 18828469
TI  - Symposium issue: prostate cancer 2008.

PMID- 18828470
TI  - Detection and diagnosis of prostate cancer.

PMID- 18828471
TI  - Robotic and laparoscopic prostatectomy.

PMID- 18828472
TI  - Arkansas hospitals: 100% committed to 5 Million Lives Campaign.

PMID- 18828473
TI  - Surgical management of prostate cancer.

PMID- 18828474
TI  - Radiotherapy for prostate cancer: role of external beam radiation.

PMID- 18828475
TI  - Cryotherapy for prostate cancer.

PMID- 18828476
TI  - Counseling the patient with prostate cancer.

PMID- 18828477
TI  - Perineal prostatectomy in the age of minimally invasive surgery.

PMID- 18828478
TI  - Brachytherapy for prostate cancer.

PMID- 18828479
TI  - Serotypes of Rhodococcus equi isolated from horses, immunocompromised human
      patients and soil in Hungary.
AB  - Two hundred and twelve Rhodococcus equi strains were isolated from soil, nasal
      and rectal swabs of horses and immunocompromised human patients in Hungary and
      serotyped using Prescott's serotyping system. One hundred and forty-seven strains
      (69.3%) belonged to serotype 1, 22 strains (10.4%) to serotype 2, 6 strains
      (2.8%) to serotype 3 and 1 strain (0.5%) to serotype 4. Serotypes 5, 6 and 7 were
      not found and 36 strains (17%) could not be typed. Serotype 1 (72%) was the type
      most commonly isolated from clinical samples of foals or from the soil of horse
      facilities. Six out of 8 R. equi strains from humans belonged to serotype 2, and
      two human strains were untypable. The data show that the prevalence of R. equi
      serotypes varies in different geographic areas of the country.

PMID- 18828480
TI  - Molecular and serological evidence of Anaplasma phagocytophilum infection of farm
      animals in the Black Sea Region of Turkey.
AB  - This study was designed to determine the presence and the prevalence of Anaplasma
      phagocytophilum infection in sheep and cattle in the Middle and Eastern Black Sea
      Regions of Turkey in which the potential vector, Ixodes ricinus, is widespread.
      Blood samples were collected from 720 sheep and 720 cattle from 6 provinces of
      the region, and used for detecting antibodies to A. phagocytophilum by indirect
      immunofluorescent antibody test (IFAT) and specific nucleic acids by a nested
      polymerase chain reaction (PCR). Blood smears were also prepared and examined
      microscopically for the presence of A. phagocytophilum-like organisms in
      polymorphonuclear cells. Of the animals examined, antibodies were detected in 110
      (15.27%) cattle and 107 (14.86%) sheep and A. phagocytophilum-like organisms were
      detected in the blood of 73 (10.13%) cattle and 71 (9.86%) sheep. In addition,
      specific DNA was detected in the blood of 27 (14.75%) cattle and 22 (12.35%)
      sheep. The results obtained constitute the first molecular and serological
      evidence of A. phagocytophilum infection in sheep and cattle in the Black Sea
      Region of Turkey.

PMID- 18828481
TI  - Evaluation of a proposed therapeutic protocol in 12 dogs with tentative
      degenerative myelopathy.
AB  - The objective of this work was to evaluate the long-term efficacy of a proposed
      therapeutic protocol in 12 dogs with a tentative diagnosis of degenerative
      myelopathy, followed-up for a 6-month period. Twelve dogs fulfilling the
      antemortem inclusion criteria (breed, age, adequate vaccination, history of
      progressive posterior ataxia and/or paraparesis, no radiographic and myelographic
      abnormalities in the spinal cord and vertebral column) were allocated. All these
      dogs presented signs of thoracolumbar syndrome (T3-L3), scored as grade I (mild
      to moderate ataxia and paraparesis) in 10 and grade II (severe ataxia and
      ambulatory paraparesis) in 2 cases. Treatment included the use of epsilon
      aminocaproic acid and N-acetylcysteine, supplemented with vitamins B, C and E.
      Prednisolone was given for the first two weeks and upon worsening of neurological
      signs. Daily exercise, performed as walking or swimming, was strongly
      recommended. Clinicopathological evaluation was normal in all 12 dogs, and survey
      radiographs and myelograms did not show spinal cord compression. Magnetic
      resonance imaging (MRI), performed only in 4 dogs, did not disclose compressive
      disorders or intramedullary lesions. Neurological signs were progressively
      worsening in all 12 animals, eventually resulting in severe paraparesis (grade
      III) or paraplegia (grade IV). The applied medications do not appear to be an
      attractive alternative to conservative management (physiotherapy) or euthanasia
      in canine degenerative myelopathy, irrespective of its chronicity.

PMID- 18828482
TI  - Passive hip laxity in Estrela Mountain Dog--distraction index, heritability and
      breeding values.
AB  - Two hundred and fifteen Estrela Mountain Dogs (EMD) were examined using the
      PennHIP method between 2002 and 2006. Passive hip laxity (PHL) was estimated
      calculating the distraction index (DI). Pedigree information was obtained from
      the Portuguese Kennel Club. The heritability and breeding values were estimated
      using the linear Animal Model. The DI, using as reference the worst joint of each
      animal, ranged from 0.15 to 1.12 (0.55 +/- 0.19). The PHL was equal in right and
      left sides, and was higher in females than in males (P > 0.05 and P <0.01 in the
      t-test, respectively). The estimated heritability was 0.83 +/- 0.11. The mean
      breeding values for PHL were stable in EMD born between 1991 and 2003, and showed
      an improvement in 2004 and 2005. The data confirm high PHL in breeds with high
      prevalence and severity of canine hip dysplasia. The high heritability indicates
      that the DI could be reduced in the breed if PHL were used as a selection
      criterion. The early favourable evolution of DI breeding values could be related
      with the increase of voluntary radiographic hip screening in the last years, and
      the subsequent introduction of hip quality as a breeding criterion.

PMID- 18828483
TI  - Cross-sectional imaging assisted selection for heart performance in pigs.
AB  - A two-way selection procedure was performed on a Landrace pig line. First the
      cardiac output (CO) values (6.89 +/- 1.27 L/min) were estimated by ECG-gated
      magnetic resonance imaging (MRI) to quantify the heart performance of the boars
      (n = 30), then total body skeletal muscle volume (MVTB; 48.7 +/- 5.17 dm3) was
      determined applying spiral computerised tomography (CT). The relative cardiac
      output value (RCO) was developed, expressing the relationship between CO and
      MVTB. Four superior [RCO value below 6.7 dm3 / (L x min(-1))] and one minus
      variant [(8.97 dm3 / (L x min(-1))] boars were taken into breeding. The best
      fifteen percentage of the first generation males (n = 30) was characterised
      according to their RCO values. Significant difference was found between the
      developed performance measure of the progenies of minus and plus variant boars
      [8.2 +/- 0.65 and 5.63 +/- 0.70 dm3 / (L x min(-1)), n = 7 and 23], respectively.
      Comparing the existing five progeny groups, all of the 'HP+' groups differed
      significantly from the 'HP-' one, where the largest heart performance contrast
      found was 3.2 dm3 / (L x min(-1)). Based upon the results, the selection is being
      continued on a larger population.

PMID- 18828484
TI  - Comparison of microsatellite and blood group diversity among different genotypes
      of cattle.
AB  - Genetic variability and relationships among five cattle breeds (Holstein,
      Pinzgau, Limousin, Slovak Spotted and Charolais) bred in the Slovak Republic were
      investigated separately using 11 microsatellite markers and 61 blood group
      systems. Allele frequency, heterozygosity (Ho, HE) and PIC values were
      investigated. F-statistics were computed separately. For microsatellite markers
      FIS, FIT, FST and for blood groups HS, HT, GST parameters were calculated.
      Microsatellite and blood group comparison showed similar results by F-statistics
      but some differences were marked using the other methods. Both methods were able
      to detect close relation between Slovak Pinzgau and Slovak Spotted cattle breeds.
      Their relation was confirmed by genetic distance, principal component analysis
      (PCA) and coefficient of admixture (mY). Important divergences between different
      markers used in the study were observed by the characterisation of Limousin and
      Charolais breeds.

PMID- 18828485
TI  - High prevalence of intestinal zoonotic parasites in dogs from Belgrade, Serbia-
      short communication.
AB  - To identify areas of risk for canine-related zoonoses in Serbia, the aim of this
      study was to provide baseline knowledge about intestinal parasites in 151 dogs
      (65 household pets, 75 stray and 11 military working dogs) from Belgrade. The
      following parasites, with their respective prevalences, were detected: Giardia
      duodenalis (14.6%), Ancylostomatidae (24.5%), Toxocara canis (30.5%), Trichuris
      vulpis (47.0%) and Taenia-type helminths (6.6%). Of all examined dogs, 75.5%
      (114/151) were found to harbour at least one parasite species. Of these, mixed
      infections with up to four species per dog occurred in 44.7% (51/114). Infections
      with all detected species were significantly higher (p < 0.05) in military
      working (100%) and stray dogs (93.3%) versus household pets (50.8%). Among all
      parasites, agents with zoonotic potential including Giardia, Ancylostomatidae and
      Toxocara were detected in 58.3% (88/151) of all examined dogs with a significant
      difference (p < 0.05) among the subgroups (100%, 62.7% and 46.2% for military
      working dogs, stray dogs and household pets, respectively). The high prevalence
      of zoonotic parasites registered in the dog population from a highly urban area
      in south-eastern Europe indicates a potential risk to human health. Thus,
      veterinarians should play an important role in helping to prevent or minimise
      zoonotic transmission.

PMID- 18828486
TI  - Expression and localisation of claudin-1, -2, -3, -4, -5, -7 and -10 proteins in
      the normal canine mammary gland.
AB  - The recently identified claudins are dominant components of tight junctions,
      responsible for cell adhesion, polarity and paracellular permeability. Certain
      claudins have been shown to have relevance in tumour development. The aim of the
      present study was to analyse the expression of claudin-1, -2, -3, -4, -5, -7 and 
      10 in normal canine mammary glands. Samples from the inguinal mammary regions of
      20 non-castrated, 1-13 years old female dogs were studied. Immunohistochemical
      analysis was performed on conventional specimens and tissue microarrays. The
      results of the immunohistochemical reactions detecting claudins in tissue
      sections were photodocumented. The immunoreactivity of claudins was
      quantitatively analysed on digital images using Leica QWin morphometry software.
      Intense membranous immunolabelling was found for claudin-1, -3 and -7, intense
      membranous with non-granular cytoplasmic immunolabelling for claudin-2, moderate
      membranous immunolabelling for claudin-4 and -5, and weak membranous
      immunolabelling for claudin-10. The occurrence of tight junctions was confirmed
      by ultrathin section electron microscopy. The available data suggested that
      claudins might be proteins preserved throughout the evolution of mammals. The
      results of our study support the concept that they are indeed preserved, since
      the same type of claudins, in identical distribution, could be detected in our
      canine mammary tissue samples as could be found in human mammary tissue.

PMID- 18828487
TI  - A survey of equine abortion and perinatal foal losses in Hungary during a three
      year period (1998-2000).
AB  - Cases of equine abortion and perinatal foal losses were investigated in Hungary
      during a three-year period (1998-2000). Samples from aborted equine fetuses and
      newborn foals (total n = 96) were examined using bacteriological, virological,
      pathological, immunohistochemical (IHC), molecular biological and serological
      methods. The cause of abortion and perinatal foal loss was identified in 67/96
      cases (70%); viral infection was found in 22 (23%), viral and bacterial
      coinfection in 1 (1%), bacterial infection in 23 (24%), protozoan infection in 1
      (1%) and fungal infection in 2 cases (2%). Morphological lesions suggestive of
      infection were recorded in 2 (2%) and non-infectious causes in 16 cases (17%).

PMID- 18828488
TI  - Physiological mechanisms of ovarian follicular growth in pigs--a review.
AB  - Follicular growth after antrum formation is determined by follicle-stimulating
      hormone (FSH). Only two ways are possible for recruited follicles, continuing
      development or atresia. In gilts, intensive ovarian follicular growth begins
      between 60 and 100 days of age, and fluctuations of the ovarian morphological
      status last about 20 days; however, at that time there are no really large
      follicles. Final follicular development is under luteinising hormone (LH)
      control; this is why the attainment of puberty is related to an increase in serum
      oestradiol to a level that causes a preovulatory surge of this gonadotropin. The
      pool of follicles at the beginning of the oestrous cycle is about 30-40, most of
      which are small (< 3 mm) and growing. Then, the pool of follicles increases to
      about 80 in the mid-luteal phase but about 50 of them are small and 30 are medium
      sized (3-6.9 mm). Some of these follicles are in the growing phase, but some are
      atretic. Between days 7 and 15 of the oestrous cycle the percentage of atretic
      follicles fluctuates between 12 and 73%. At that time there are no large (> 7 mm)
      follicles because of the suppressing effect of progesterone. The number of small
      follicles declines after luteolysis. From the pool of medium follicles, large
      follicles are selected under the influence of LH, but about 70% of the medium
      sized follicles become atretic. Because of the long-lasting selection process
      there is a significant heterogeneity in the diameter of large follicles in
      oestrus. However, the number of follicles correlates with the number of corpora
      lutea after ovulation. Individual follicular development and the relationship
      between follicles are still poorly known. The use of ultrasonography may give a
      closer insight into these phenomena.

PMID- 18828489
TI  - Effects of dietary meals containing different levels of phytoestrogens on
      reproductive function in Bilgoraj ganders.
AB  - The aim of this study was to investigate how long-term feeding of ganders with
      diets containing different levels of phytoestrogens affects the morphometry of
      testes, plasma steroid levels, sperm parameters and reproductive performance.
      Male Bilgoraj geese were fed diets containing grass meal (with low phytoestrogen
      levels) and those containing alfalfa meal and soybean meal (with higher levels of
      phytoestrogens). Testes were obtained from ganders at the peak of mating and the
      ongoing laying period as well as at the beginning of photorefractoriness. The
      morphometric parameters were measured in frozen testicular sections. Blood was
      collected monthly from December to June, and plasma testosterone, androstenedione
      and corticosterone concentrations were determined. During the mating season,
      semen was collected and its quantity and quality were investigated. In the flocks
      (ganders with geese) reproductive output was noted. Seasonal changes were
      observed in the morphology of testes and in plasma testosterone, androstenedione
      and corticosterone concentrations in ganders. The feeding of ganders with dietary
      meals containing higher levels of phytoestrogens did not affect the plasma
      steroid contents or the majority of the morphometric parameters of testes, except
      for the height of the seminiferous epithelium, which was lowered. Moreover, diets
      with higher levels of phytoestrogens decreased the volume of ejaculates and the
      percentage of normal spermatozoa. However, these changes were not reflected in
      the fertilisation rates.

PMID- 18828490
TI  - Synchronisation of lambing with low doses of dexamethasone in Chios ewes--short
      communication.
AB  - The purpose of the present study was to investigate the feasibility of improving
      the synchronisation of lambing after oestrus synchronisation and artificial
      insemination (AI). To this end, low doses of dexamethasone 21-isonicotinate (DEX)
      alone or in combination with prostaglandin F2a (PG) were used in five treated
      groups (n = 20 each) and one control group (n = 136) of Chios ewes. On day 143 of
      pregnancy 1.5 mg DEX was given in Group 5, while on day 146 the following
      treatments were applied: 0.0375 mg PG in Groups 4 and 5, and 1, 1.5 and 2 mg of
      DEX in ewes of Groups 1, 2 and 3, respectively. The control ewes received no
      treatment. The 1.5 and 2 mg dose of DEX was more effective in synchronising
      labour as regards the treatment to lambing interval and the proportion of ewes
      that gave birth within 3 days. However, obstetrical manipulations were needed,
      and dead lambs were born when 2 mg DEX was used. It was concluded that lambing
      can be safely synchronised in Chios ewes with 1.5 mg DEX given on day 146,
      without affecting the viability of lambs and without parturition complications.

PMID- 18828491
TI  - Vitrification of in vitro matured oocytes of Mangalica and Large White pigs.
AB  - The breeding of Mangalica, a native pig breed in Hungary, had been started in
      1833, but this pig breed almost became extinct in Hungary in the past decades. In
      1991, the number of sows was only 200. Although in these days the existing
      Mangalica population consists of more than 6000 animals representing different
      colour variations, the preservation of this traditional pig breed is still very
      important. Vitrification is a potential tool for the preservation of gametes and
      embryos of these animals. The aim of this study was to investigate the effects of
      vitrification on the developmental competence of Mangalica (M) and Large White
      (LW) oocytes following fertilisation. The oocytes were vitrified by the Open
      Pulled Straw (OPS) method using different concentrations of ethylene glycol and
      dimethyl sulphoxide as cryoprotectants. After rehydration the oocytes underwent
      in vitro fertilisation; the resultant zygotes were then cultured in vitro for
      four days to assess embryonic development. In the first experiment, in vitro
      maturation of M and LW oocytes was compared. No significant difference was
      observed in the nuclear maturation rate of LW and M oocytes. In the second
      experiment, the sensitivity of oocytes to vitrification was examined by
      evaluating oocyte morphology after thawing. A higher percentage of LW oocytes
      showed normal morphology compared to M oocytes, indicating that Mangalica oocytes
      are more sensitive to cryoprotectants than Large White oocytes. After warming and
      in vitro fertilisation, more than 50% of the oocytes started embryonic
      development and by the end of the incubation period morula stage embryos had
      developed in both groups. The results show that the OPS vitrification technique
      is well suited to preserve Mangalica oocytes and from these oocytes morula
      embryos can be produced.

PMID- 18828492
TI  - Experimental results and clinical impact of using autologous rectus fascia sheath
      for vascular replacement.
AB  - Vascular complications are major causes of graft failure in liver
      transplantation. The use of different vascular grafts is common but the results
      are controversial. The aim of this study was to create an 'ideal' arterial
      interponate for vascular replacements in the clinical field. An autologous,
      tubular graft prepared from the posterior rectus fascia sheath was used for iliac
      artery replacement in dogs for 1, 3, 6 and 12 months. Forty-one grafts were
      implanted and immunosuppression was used in separate groups. The patency rate was
      followed by Doppler ultrasound. Thirty-seven grafts remained patent, 2 cases with
      thrombosis and 2 cases with stenosis occurred. There was no evidence of necrosis
      or aneurysmatic formation. The histological analysis included conventional light
      microscopic and immunohistochemical examinations for CD34 and factor VIII. The
      explanted grafts showed signs of arterialisation, appearance of elastin fibres,
      and smooth muscle cells after 6 months. Electron microscopy showed intact
      mitochondrial structures without signs of hypoxia. In conclusion, the autologous
      graft presents acceptable long-term patency rate. It is easy to handle and the
      concept of beneficial presence of the anti-clot mesothelium until
      endothelialisation seems to work. The first clinical use was already reported by
      our group with more than 2 years survival.

PMID- 18828493
TI  - Replication and transmission of porcine circovirus type 2 in mice.
AB  - Little information is known about infection, replication and transmission of
      porcine circovirus type 2 (PCV2) in species other than swine. Two sets of animal
      experiments were carried out to investigate the susceptibility of mice to PCV2
      and to study their possible role in maintaining and transmitting the virus. In
      the first experiment 14 mice were inoculated with PCV2 by the intraperitoneal
      route with 5 x 10(2) TCID50 of the PCV2-ROM strain (Cadar et al., 2007). In a
      second experiment 24 mice were divided into two groups (A and B); mice in Group A
      (n = 18) were inoculated orally with 1 x 10(5) TCID50 PCV2-ROM and mice in Group
      B (n = 6) were left uninoculated until day 12 post inoculation (p.i.), when they
      were mixed with Group A. The animals were sacrificed at intervals for postmortem
      investigation and virus genome detection by polymerase chain reaction (PCR). The
      PCR results indicated that PCV2 could replicate in mice infected
      intraperitoneally or by the oral route, and that the virus can be transmitted
      directly from mouse to mouse.

PMID- 18828494
TI  - Allergens and allergen immunotherapy. Preface.

PMID- 18828495
TI  - Allergen immunotherapy in historical perspective.

PMID- 18828496
TI  - Definition of an allergen (immunobiology).

PMID- 18828497
TI  - Allergen nomenclature.

PMID- 18828498
TI  - Immunologic responses to subcutaneous allergen immunotherapy.

PMID- 18828499
TI  - Immunologic responses to sublingual allergen immunotherapy.

PMID- 18828500
TI  - Tree pollen allergens.

PMID- 18828501
TI  - Grass pollen allergens.

PMID- 18828502
TI  - Weed pollen allergens.

PMID- 18828503
TI  - Fungal allergens.

PMID- 18828504
TI  - Mite allergens.

PMID- 18828505
TI  - Cockroach and other inhalant insect allergens.

PMID- 18828506
TI  - Mammalian allergens.

PMID- 18828507
TI  - Food allergens.

PMID- 18828508
TI  - Hymenoptera allergens.

PMID- 18828509
TI  - Biting insect allergens.

PMID- 18828510
TI  - Occupational allergens.

PMID- 18828511
TI  - Standardized allergen vaccines in the United States.

PMID- 18828512
TI  - Manufacturing and standardizing allergen extracts in Europe.

PMID- 18828513
TI  - Preparing and mixing allergen vaccines for subcutaneous immunotherapy.

PMID- 18828514
TI  - Subcutaneous administration of allergen vaccines.

PMID- 18828515
TI  - Administration of sublingual vaccines.

PMID- 18828516
TI  - Subcutaneous immunotherapy for allergic rhinoconjunctivitis, allergic asthma, and
      prevention of allergic diseases.

PMID- 18828517
TI  - Sublingual immunotherapy for allergic Rhinoconjunctivitis, allergic asthma, and
      prevention of allergic diseases.

PMID- 18828518
TI  - Immunotherapy for hymenoptera venom hypersensitivity.

PMID- 18828519
TI  - Experimental forms of allergen immunotherapy with modified allergens and
      adjuvants.

PMID- 18828520
TI  - Anti-IgE therapy.

PMID- 18828521
TI  - Immunotherapy for food and latex allergy.

PMID- 18828522
TI  - Unproven and controversial forms of immunotherapy.

PMID- 18828523
TI  - Adverse effects and fatalities associated with subcutaneous allergen
      immunotherapy.

PMID- 18828524
TI  - Adverse effects associated with sublingual immunotherapy.

PMID- 18828525
TI  - Prevention and treatment of anaphylaxis.

PMID- 18828526
TI  - Instructions and consent forms for subcutaneous allergen immunotherapy.

PMID- 18828527
TI  - Information and consent forms for sublingual immunotherapy.

PMID- 18828528
TI  - Nursing that works. Bridging the gap between organizational policies and
      practice. Interviewed by Diane E Scott.

PMID- 18828529
TI  - Legal strategies for nurses.

PMID- 18828530
TI  - Forecasting nurse supply, demand, and shortage, 2007-2020.

PMID- 18828531
TI  - Career choice making: what should influence your decision.

PMID- 18828532
TI  - Communicating with physicians.

PMID- 18828533
TI  - [Scientific evidence in occupational health: meta-analytical study of the burnout
      syndrome].
AB  - BACKGROUND: According to scientific literature, burnout can be described as a
      multi-dimensional syndrome with three fundamental dimensions: emotional
      exhaustion, depersonalization and reduced personal accomplishment. OBJECTIVES:
      Since attention for this phenomenon is increasing, with a large number of
      articles published in scientific journals in recent years, we set out to evaluate
      the scientific evidence on this topic by applying the meta-analytical method.
      METHODS: All comparative studies performed on burnout were identified and
      examined in order to compute the Effect Size of the results. Forty studies
      complied with the inclusion criteria of this analysis for a total of 2,031
      burnout cases versus 1,950 controls. RESULTS: Our results revealed a significant
      disparity in the methods of selecting subjects with burnout. This problem
      emphasizes the lack of a standardized definition of burnout as a univocal
      clinical entity and, consequently, the lack of a unanimously agreed procedure for
      the identification of patients to be included in this diagnostic category.
      CONCLUSIONS: The wide heterogeneity between studies thus considerably reduces the
      possibility of comparing them and generalizing the results.

PMID- 18828534
TI  - [Upper-limb work-related musculoskeletal disorders (UL-WMSDs) and latency of
      effect].
AB  - BACKGROUND: Trends in work-related upper limb musculoskeletal disorders appear to
      be in constant increase in industrialized countries. In Europe claims and
      compensation for these disorders have significantly increased. OBJECTIVE: The aim
      of this study was to investigate the temporal relationship between the beginning
      of occupational exposure to repetitive movements and exertions of upper limbs,
      assessed through the OCRA index, and the manifestation of the disorders. METHODS:
      Clinical and questionnaire information about 557 cases of UL-WMSDs in the
      upholstered furniture industry were analyzed in order to investigate the mean
      latency period of the disorders and to verify to what extent different levels of
      exposure influence the latency time. RESULTS AND CONCLUSIONS: The latency of UL
      WMSDs is influenced by the level of exposure to risk, measured by means of the
      OCRA index. Shorter latency times were found for wrist/hand tendonitis, with a
      mean latency time of 5.4 years and with a greater sensitivity to the level of
      exposure assessed with the OCRA index value. This might support a sort of
      predictive value with reference to other UL-WMSDs with longer latency. Probably a
      latency period of 12 years may be suggested as the cut-off limit to assess a
      causal relationship between tendon or canalicular WMISDs and occupational
      exposure to repetitive movements and exertions of upper limbs.

PMID- 18828535
TI  - [Music through earphones: an underestimated risk].
AB  - BACKGROUND: The authors studied exposure to the noise generated by digital music
      listening devices (MP3) as used by young people. OBJECTIVES: to study the level
      of sound emission of some of these devices at 100%, 75% and 50% volume. METHODS:
      Using a mannequin, the LeqA, LmaxA, LeqC and the peak in C of nine of the most
      commonly used devices was measured at levels of sound emission of 100%, 75% and
      50%. RESULTS: It was found that all the devices exceeded 100 dBA of Leq at 100%
      of the listening volume. We therefore estimated the Lex8, as recommended in
      Italian Law 195/06, to which these young people are exposed using the devices for
      15, 30, and 60 minutes/day. CONCLUSIONS: Young people undergoing daily exposures
      for only 15 minutes at maximal listening volume exceed the limit value of daily
      occupational exposure for workers, which Law 195/06 fixes at 87 dBA.

PMID- 18828536
TI  - Health investigations of depleted-uranium clean-up workers.
AB  - BACKGROUND: The soil contaminated by depleted uranium (238U) ammunition during
      the NATO bombing of Serbia and Montenegro was cleaned-up for four months in 2002.
      A team of 11 clean-up workers (expert members) were medically examined three
      times: before decontamination as a preliminary medical check-up, immediately
      after decontamination, and four years after cleaning up contaminated ground.
      OBJECTIVES: This short report presents investigations and health risk assessments
      of clean-up workers in radioactive decontamination operations and an assessment
      of the environmental health perspectives for citizens living in surrounding
      areas. METHOD: The method of initial health disorders was used, analyzing the
      most sensitive biological materials, such as blood cells or chromosome damage,
      DNA strand breaks, radio-toxicological examination of urine. RESULTS: The total
      number of blood cells did not change, but variations of the relative number
      (percentage) of cells in the leukocyte formula were observed. The total number of
      DNA alterations was higher immediately after decontamination than before
      decontamination. Four years after decontamination the number of DNA alterations
      had decreased. However, the number of damaged cells (lymphocytes containing
      chromosome lesions) was higher in both medical examinations, immediately after
      and four years after decontamination. CONCLUSIONS: Disease or tumours due to 238U
      did not develop in the group of depleted uranium clean-up workers during the
      investigation period of four years. Further monitoring of haematological and
      chromosomal effects and the health condition of workers is necessary.

PMID- 18828537
TI  - [Determining factors of job-satisfaction: presence of work-family conflict in a
      sample of Italian nurses].
AB  - BACKGROUND: Organization research has shown increasing interest in the dynamics
      of work-family conflict (w.f.c.). The NEXT study highlights that w.f.c.
      significantly influences satisfaction for one's job and the decision to quit the
      nursing profession. OBJECTIVES: This study analyzes w.f.c. in a sample of Italian
      nurses, with the aim of examining the main differences in relation to personal
      variables, and understanding the degree to which w.f.c. explains job
      satisfaction. METHODS: A self-reporting questionnaire was administered to 325
      nurses in different hospitals of Northern Italy. Descriptive, reliability and
      Anova data analysis was performed. The relationships between variables were
      analyzed through correlations (Pearson's r); the role of w.f.c. in explaining job
      satisfaction was estimated via multiple regression. RESULTS: W.f.c. appeared to
      be more critical in subjects who had care responsibilities and in those who had
      more demanding work assignments. W.f.c. contributed to explaining job
      satisfaction, even if it was not its principal determining factor. CONCLUSIONS:
      This area of research appears to be important in that it leads to a better
      comprehension of the dynamics involved in work satisfaction and can suggest
      possible initiatives for support and development.

PMID- 18828539
TI  - [In search of the lost (or squandered?) occupational diseases].

PMID- 18828538
TI  - [Consensus Document. Update on latex exposure and use of gloves in Italian health
      care settings].
AB  - This consensus document was prepared by an Italian working group including
      occupational health professionals involved for many years in the management of
      glove- and latex-related problems in health care settings. The aim of this
      document was to address the most significant technical, epidemiological,
      clinical, environmental and prevention problems related to the use of gloves and
      latex. The group's recommendations are based on scientific evidence and practical
      experience but they cannot be considered as final. These topics need to be
      periodically revised. The following points should be taken into account: glove
      quality seems to have improved considerably but the information on glove features
      provided by the manufacturers is often still inaccurate or incomplete; the
      regulations in force provide that the manufacturers perform tests to supply
      evidence for the quality of the products but they do not indicate which
      analytical method should be used and they do not require that the results be
      reported in the technical data sheets. Thus the manufacturers have only to
      declare that their products are "in accordance with the rules"; therefore,
      purchasers should require the manufacturing companies to supply detailed
      information and verify their reliability. Moreover, the rules should be adapted
      to higher quality standards; occupational physicians must be involved for the
      correct choice and purchase of protective gloves; the use of gloves (in
      particular latex gloves) and latex devices in health care settings should be
      based on specific criteria: procedures must be available stating which kind of
      gloves are suitable for specific tasks. When exposure to latex cannot be avoided
      it is necessary to choose products that have good biocompatibility (e.g., powder
      free-gloves with low allergen content); once and for all latex powdered gloves
      should no longer be commercially available! labels for latex devices (including
      gloves) should report the extractable latex allergen content. Limit values for
      extractable latex allergens should be established; the use of synthetic rubber
      gloves should be encouraged since some materials (e.g., neoprene and nitrile
      rubber) appear to have physical properties and protective efficacy similar to
      latex, plus good biocompatibility; more studies should be promoted to verify the
      protective efficacy of new synthetic materials; health care workers should be
      informed about the advisability and usefulness of using materials other than
      latex; health care services should not cause additional risks but rather
      highlight the advantages for workers and patients if the use of latex gloves and
      devices is minimized.

PMID- 18828540
TI  - [Research in epidemiology: the fate of junior scientists].

PMID- 18828541
TI  - [Corporate influences on epidemiology].

PMID- 18828542
TI  - [A point of view from nowhere?].

PMID- 18828543
TI  - [Future relationship between epidemiologists and business: the case of
      nutrition].

PMID- 18828544
TI  - [Keeping in touch with local communities as an antidote to corporate influences].

PMID- 18828545
TI  - Using the freedom we have, strengthening democracy, widening transparency,
      practising disclosure and increasing the scientific level of epidemiologic
      research: how much do we want to achieve in the next 10 years?

PMID- 18828546
TI  - [How to compensate asbestos victims: different experiences].

PMID- 18828547
TI  - [Compensating asbestos victims: the French model].

PMID- 18828548
TI  - [Light and shadow of the Dutch Institute for asbestos victims].

PMID- 18828549
TI  - [A multilateral consensus on how to use hormone replacament therapy and how to
      inform women].

PMID- 18828550
TI  - [Numbers (Airtum Working Group). Survival prospects change with time].

PMID- 18828551
TI  - [Brescia Local Health Autority Population Database: a method based on current
      data for monitoring chronic diseases and management].
AB  - OBJECTIVE: The Local Health Autority (ASL) of Brescia has activated an innovative
      method of surveillance, based on the integration ofcurrent databases in a single
      database, Population Database (BDA), for monitoring the prevalence of chronic
      diseases in the area. METHOD: The BDA has been set up using automatic record
      linkages of databases regarding disease exemptions, drug treatments, hospital
      admissions and outpatient specialist visits. This enabled us to calculate the
      prevalence of various chronic diseases (single or grouped) and the gross average
      expenditure per person for each disease group. RESULTS: Out of the 1,092,201
      people in the Brescia ASL, 275,601 had at least one chronic disease (prevalence
      252.3/1,000). Diseases ofthe circulatory system were the most frequent
      (169.1/1,000), followed by diabetes mellitus (36 6/1,000). Having had an organ
      transplant was the condition with the highest per-person expenditure (Euro
      16,170/year). The highest total expenditure was associated with circulatory
      diseases, because of the high prevalence (Euro 470,377,413). CONCLUSION: A single
      computerised data base is capable of achieving epidemiological aims (assessing
      population health status) as well as managerial and health care aims (resources
      management, control of the appropriateness of services, adaptation of diagnostic
      therapeutic methods to international guidelines and standards).

PMID- 18828552
TI  - [Review of epidemiological studies of cancer risk among Gulf War and Balkans
      veterans].
AB  - OBJECTIVE: Analysis of the available epidemiological evidence on cancer risk
      among Gulf war and Balkans veterans. DESIGN AND SETTING: Eligible for the review
      were all studies published in peer-reviewed journals indexed in MedLine by the
      end of 2007. The review includes twelve studies published between 1996 and 2006
      All of them are retrospective cohort studies focused on different outcomes:
      mortality, hospitalizations or cancer incidence. The study populations are from
      US, UK, Sweden, Denmark and Italy. The description ofthe studies reviewed
      focusses on their main features (design, study population, health outcomes and
      ascertainment procedures, analytical methods). RESULTS: Results are summarized by
      cancer site: all cancers, neoplasms that may be a target of exposure to depleted
      uranium (lung cancer, leukemias, kidney cancer, bone cancer), and other neoplasms
      (lymphomas, brain cancer, and cancer of the testis) relatively frequent among
      young adults. The overall incidence of cancers is not increased in the cohort
      studies of Gulf war and Balkans veterans published to date, nor there is
      consistent evidence of excess risks of neoplasms possibly related to exposure to
      depleted uranium. However, in the Danish cohort of Balkans veterans an increased
      risk ofbone cancer has been observed, but the excess disappeared when a 1-year
      latency was considered. An increased brain cancer risk in relation to exposure to
      nerve-gas agents has been observed. Sporadic excesses of Hodgkin lymphoma and
      testicular cancer in deployed veterans have been reported. CONCLUSION: None of
      the studies reviewed could obiectively assess exposures to depleted uranium or to
      other potentially carcinogenic agents experienced in the theaters. The study
      cohorts are young and the follow-up periods are probably too short to capture
      excesses of long latency outcomes. The update of the follow-up of the cohorts and
      studies of other cohorts with a better assessment of exposure to depleted uranium
      and to other potentially relevant risk factors are warranted.

PMID- 18828553
TI  - [Community interventions among tobacco control strategies: coping with their
      definition and evaluation].
AB  - Community interventions represent a key component of the current anti-smoking
      strategies. We propose a conceptual framework for classifying these
      interventions, based on the concept of community utilised in different studies.
      We identified 5 different focuses: geographical areas (i.e. city, county,
      region); targets (sub-group of a population); settings (school, workplace);
      culture and individual attitudes; multilevel networks. These two latter views
      refer to functional rather than to structural aspects of a community and they
      represent the most promising approaches to design intervention strategies.
      Communities are represented as a group of organizations, systems and social
      networks investigating individual, environmental and cultural factors that can
      strongly influence behavioural changes. The great heterogeneity in what the
      authors mean as community interventions has in our opinion affected the
      evaluation of their impact. To facilitate their evaluation and to contribute to
      the detection of determinants, as well as of barriers, it is necessary to compare
      community interventions sharing similar theoretical approaches and focuses. Also,
      studies aimed at assessing the steps of the implementation process of community
      programmes may allow to identify those components related to specific levels of
      intervention, thus enabling the generalisation of results. To reach this goal it
      may be helpful to combine study designs allowing for both quantitative and
      qualitative assessments, such as action research and participatory evaluation
      research.

PMID- 18828554
TI  - [Multiple imputation for missing data: a brief introduction].

PMID- 18828555
TI  - [Bioclimatic warning systems: the experience of Emilia-Romagna].

PMID- 18828556
TI  - [To study fatal occupational injuries in Italy: is it possible?].

PMID- 18828557
TI  - [How to assess the effects of interventions for preventing work injuries?
      Observations on INAIL-ISPESL-Regioni indicators].

PMID- 18828558
TI  - Marine vertebrate zoonoses: an overview of the DAO special issue.
AB  - The role of marine birds, mammals, turtles and fish as vectors of infectious
      agents of potential risk to humans can be examined from a variety of
      perspectives. The studies in this DAO Special include a broad survey of multiple
      agents and species, a sequencing study of Giardia intestinalis haplotypes known
      to be pathogenic to humans, an assessment of risks to humans working with marine
      mammals, a source tracking study using E. coli ribotypes, studies of regional
      Salmonella and Brucella epizootiology, a serology survey and a case report of a
      herpes simplex infection in a dolphin. Additionally, a recently published study
      (Venn-Watson et al. 2008; Dis Aquat Org 79:87-93) classifying pure cultures of
      bacteria from a captive dolphin colony also pertains to this theme. These studies
      raise the following questions: whether the presence of zoonotic agents in marine
      vertebrates represents a risk to other marine vertebrates, humans, or both; what
      are the routes by which these marine vertebrate zoonotic infections are acquired
      and circulated in the marine ecosystem; to what degree are such agents
      subclinical versus causes of overt disease in marine vertebrates; what are the
      subsets of the human population most likely to be affected by such infections;
      and which human health preventive measures would seem reasonable?

PMID- 18828559
TI  - Prevalence and characterization of Salmonella spp. among marine animals in the
      Channel Islands, California.
AB  - Salmonella enterica is a zoonotic pathogen that has been isolated from free
      ranging marine mammals throughout the world, with animals in the Channel Islands
      of California (USA) showing the highest prevalence. The goal of this study was to
      determine prevalence, antimicrobial sensitivity and genetic similarity using
      pulsed-field gel electrophoresis (PFGE) of Salmonella in several non-domestic
      animal species on San Miguel and San Nicolas Islands. Fecal samples were
      collected from 90 California sea lion Zalophus californianus pups, 30 northern
      elephant seal Mirounga angustirostris pups and 87 western gulls Larus
      occidentalis in the Channel Islands and 59 adult male sea lions in Puget Sound,
      WA (USA). Salmonella were isolated, identified and serotyped, followed by
      antimicrobial susceptibility testing and PFGE. Of the California sea lion pups
      that were sampled on the islands, 21% (n = 19) were positive for Salmonella,
      whereas no adults males in Puget Sound were positive. Of the northern elephant
      seal pups sampled, 87% (n = 26) were harboring Salmonella. Only 9% (n = 8) of
      western gulls were shedding Salmonella, with one of these gulls harboring the
      only antimicrobial resistant isolate. The serotypes found in these animals were
      Enteritidis, Montevideo, Newport, Reading, and Saint Paul. The only serotype that
      showed variation on PFGE was Newport. The pinnipeds of the Channel Islands harbor
      Salmonella at a higher prevalence than pinnipeds from other geographic areas
      observed in previous studies. Researchers and veterinarians should exercise
      increased caution when working with these animals due to the zoonotic potential
      of Salmonella.

PMID- 18828561
TI  - Molecular characterization of Giardia intestinalis haplotypes in marine animals:
      variation and zoonotic potential.
AB  - Giardia intestinalis is a microbial eukaryotic parasite that causes diarrheal
      disease in humans and other vertebrates worldwide. The negative effect on quality
      of life and economics caused by G. intestinalis may be increased by its potential
      status as a zoonosis, or a disease that can be transmitted from animals to
      humans. The zoonotic potential of G. intestinalis has been implied for over 2
      decades, with human-infecting genotypes (belonging to the 2 major subgroups,
      Assemblages A and B) occurring in wildlife and domesticated animals. There are
      recent reports of G. intestinalis in shellfish, seals, sea lions and whales,
      suggesting that marine animals are also potential reservoirs of human disease.
      However, the prevalence, genetic diversity and effect of G. intestinalis in
      marine environments and the role that marine animals play in transmission of this
      parasite to humans are relatively unexplored. Here, we provide the first thorough
      molecular characterization of G. intestinalis in marine vertebrates. Using a
      multi-locus sequencing approach, we identify human-infecting G. intestinalis
      haplotypes of both Assemblages A and B in the fecal material of dolphins,
      porpoises, seals, herring gulls Larus argentatus, common eiders Somateria
      mollissima and a thresher shark Alopias vulpinus. Our results indicate that G.
      intestinalis is prevalent in marine ecosystems, and a wide range of marine hosts
      capable of harboring zoonotic forms of this parasite exist. The presence of G.
      intestinalis in marine ecosystems raises concerns about how this disease might be
      transmitted among different host species.

PMID- 18828560
TI  - Victims or vectors: a survey of marine vertebrate zoonoses from coastal waters of
      the Northwest Atlantic.
AB  - Surveillance of zoonotic pathogens in marine birds and mammals in the Northwest
      Atlantic revealed a diversity of zoonotic agents. We found amplicons to sequences
      from Brucella spp., Leptospira spp., Giardia spp. and Cryptosporidium spp. in
      both marine mammals and birds. Avian influenza was detected in a harp seal and a
      herring gull. Routine aerobic and anaerobic culture showed a broad range of
      bacteria resistant to multiple antibiotics. Of 1460 isolates, 797 were tested for
      resistance, and 468 were resistant to one or more anti-microbials. 73% (341/468)
      were resistant to 1-4 drugs and 27% (128/468) resistant to 5-13 drugs. The high
      prevalence of resistance suggests that many of these isolates could have been
      acquired from medical and agricultural sources and inter-microbial gene transfer.
      Combining birds and mammals, 45% (63/141) of stranded and 8% (2/26) of by-caught
      animals in this study exhibited histopathological and/or gross pathological
      findings associated with the presence of these pathogens. Our findings indicate
      that marine mammals and birds in the Northwest Atlantic are reservoirs for
      potentially zoonotic pathogens, which they may transmit to beachgoers, fishermen
      and wildlife health personnel. Conversely, zoonotic pathogens found in marine
      vertebrates may have been acquired via contamination of coastal waters by sewage,
      run-off and agricultural and medical waste. In either case these animals are not
      limited by political boundaries and are therefore important indicators of
      regional and global ocean health.

PMID- 18828562
TI  - Characterization of Escherichia coli populations from gulls, landfill trash, and
      wastewater using ribotyping.
AB  - Due to their opportunistic and gregarious nature, gulls may be important
      reservoirs and vectors for anthropogenically derived fecal pathogens in coastal
      areas. We used ribotyping, a genotypic bacterial source tracking method, to
      compare populations of Escherichia coli among herring gulls Larus argentatus,
      great black-backed gulls L. marinus, wastewater, and landfill trash in New
      Hampshire and Maine, USA. Concentrations of E. coli in gull feces varied widely
      among individuals, but were generally high (6.0 x 10(1) to 2.5 x 10(9) g(-1) wet
      weight). Of 39 E. coli isolates from L. argentatus, 67% had banding patterns that
      were > or = 90% similar to those from wastewater and trash, whereas only 39% of
      36 L. marinus isolates exhibited > or = 90% similarity to these sources. Strains
      of E. coli from gulls matched (> or = 90% similarity) more strains from
      wastewater (39% matching) than from trash (15% matching). E. coli isolates from
      L. marinus feces exhibited a greater diversity of banding patterns than did
      isolates from L. argentatus. There were more unique E. coli banding patterns in
      trash samples than in wastewater, and higher diversity indices in the former
      compared to the latter. These findings suggest that both species of gulls,
      especially L. argentatus, obtain fecal bacteria from wastewater and landfill
      trash, which they may transport to recreational beaches and waters. Our results
      also indicate that E. coli populations may vary widely between gull species, and
      between the anthropogenic habitats that they frequent, i.e. landfills and
      wastewater treatment facilities.

PMID- 18828563
TI  - Incidence of Brucella species in marine mammals of the German North Sea.
AB  - In this study, organ samples from 426 common seals Phoca vitulina, 298 harbour
      porpoises Phocoena phocoena, 34 grey seals Halichoerus grypus and 10 other marine
      mammals were assessed for the presence of Brucella species. Forty-seven common
      seals, 2 harbour porpoises and 1 grey seal were found to be positive for these
      bacteria. A total of 91 Brucella strains were successfully isolated, due to the
      fact that Brucella spp. were found in more than one organ sample in 15 animals.
      The primary organ in which the bacteria were present was the lung. In addition, 2
      strains were isolated from lungworms (Parafilaroides spp.). Forty-nine of the
      isolated strains were selected for further analysis using conventional
      phenotyping methods. Molecular characterisation was carried out by analysing the
      IS711 and omp2 loci. With respect to the distribution of the IS711 loci in the
      genome, the 49 field isolates differed strongly from the terrestrial Brucella
      species and marginally from the marine Brucella reference strain NCTC12890. Based
      on the results of the PCR restriction fragment length polymorphism (PCR-RFLP)
      investigation of the omp2 locus, the majority of the Brucella field isolates were
      classified as B. pinnipediae, recently proposed B. pinnipedialis, possessing 1
      omp2a gene and 1 omp2b gene. Two field isolates revealed the presence of 2 omp2a
      genes, as has been described for Brucella ovis. To our knowledge, these results
      confirm for the first time the presence of Brucella species in the marine mammal
      population of the German North Sea. These findings highlight the need for
      additional research on the relevance of these Brucella species for marine hosts
      and their environment.

PMID- 18828564
TI  - Herpes simplex-like infection in a bottlenose dolphin stranded in the Canary
      Islands.
AB  - A bottlenose dolphin, stranded in the Canary Islands in 2001 exhibited non
      suppurative encephalitis. No molecular detection of cetacean morbillivirus (CeMV)
      was found, but a herpesviral-specific band of 250 bp was detected in the lung and
      brain. The sequenced herpesviral PCR product was compared with GenBank sequences,
      obtaining 98% homology (p-distance of 0.02) with Human herpesvirus 1 (herpes
      simplex virus 1 or HSV-1). This is the first report of a herpes simplex-like
      infection in a stranded dolphin.

PMID- 18828565
TI  - Viral and bacterial serology of six free-ranging bearded seals Erignathus
      barbatus.
AB  - Serum or heparinized plasma samples were obtained from 3 male (2 adult and 1
      weaned calf) and 3 adult female free-ranging bearded seals Erignathus barbatus in
      May of 1994, 1995, or 1996. Blood samples were obtained from animals taken in
      subsistence hunts near St. Lawrence Island, Alaska and screened for antibodies to
      a suite of bacteria and viruses potentially pathogenic for pinnipeds and/or
      humans. No samples had detectable antibodies to Brucella spp., Phocine distemper
      virus, influenza A virus or caliciviruses (San Miguel sea lion virus strains 1,
      2, and 4 to 13, vesicular exanthema of swine serotypes A48, B51, C52, D53, E54,
      F55, G55, H54, 155, J56, K54, 1934B, and Tillamook and Walrus calicivirus). One
      seal had a low titer of 100 to Leptospira interrogans serovar

PMID- 18828566
TI  - Health risks for marine mammal workers.
AB  - Marine mammals can be infected with zoonotic pathogens and show clinical signs of
      disease, or be asymptomatic carriers of such disease agents. While isolated cases
      of human disease from contact with marine mammals have been reported, no
      evaluation of the risks associated with marine mammal work has been attempted.
      Therefore, we designed a survey to estimate the risk of work-related injuries and
      illnesses in marine mammal workers and volunteers. The 17-question survey asked
      respondents to describe their contact with marine mammals, injuries sustained,
      and/or illnesses acquired during their period of marine mammal exposure. Most
      respondents, 88% (423/483), were researchers and rehabilitators. Of all
      respondents, 50% (243/483) reported suffering an injury caused by a marine
      mammal, and 23% (110/483) reported having a skin rash or reaction. Marine mammal
      work-related illnesses commonly reported included: 'seal finger' (Mycoplasma spp.
      or Erysipelothrix rhusiopathiae), conjunctivitis, viral dermatitis, bacterial
      dermatitis, and non-specific contact dermatitis. Although specific diagnoses
      could not be confirmed by a physician through this study, severe illnesses were
      reported and included tuberculosis, leptospirosis, brucellosis, and serious
      sequelae to seal finger. Risk factors associated with increased odds of injury
      and illness included prolonged and frequent exposure to marine mammals; direct
      contact with live marine mammals; and contact with tissue, blood, and excretions.
      Diagnosis of zoonotic disease was often aided by veterinarians; therefore,
      workers at risk should be encouraged to consult with a marine mammal veterinarian
      as well as a physician, especially if obtaining a definitive diagnosis for an
      illness becomes problematic.

PMID- 18828567
TI  - A hybrid body technique: does the pulse diagnostic cun guan chi method have
      Chinese-Tibetan origins?
AB  - This article investigates the medieval origins of the main pulse diagnostic
      method in contemporary Chinese medicine, sometimes known as san bu (three
      sectors) method, which requires physicians to examine the mai (vessels, vessel
      movements or pulse) on the wrist at the three locations cun guan chi (inch, gate,
      foot). The article provides evidence to suggest that this body technique grew out
      of an earlier Chinese one, the cun chi (inch-foot) method, which appears to have
      aimed at investigating the qualities of yin and yang in order to determine the
      condition of a patient by means of exploring fairly large areas of the patient's
      body surface with the palms. The article furthermore posits that the cun chi
      method was decisively transformed in medieval times, presumably due to the impact
      of early Tibetan pulse diagnostic practices: it became framed in a numerology of
      three and started advocating the use of the fingertips for sensing the pulse
      beats. The article, which draws on detailed textual analyses of medieval
      manuscripts, on visual evidence and also on psychophysical research, furthermore
      highlights how misunderstandings can constructively contribute to cultural
      communication.

PMID- 18828568
TI  - Spanish influenza in the heart of Europe. A study of a significant sample of the
      Basque population.
AB  - This article presents calculations and comparisons of mortality rates for
      influenza, for diseases of the respiratory system (with the exception of
      tuberculosis) and for all the causes of death, in 21 locations in the Basque
      Country (between Spain and France). The data were collected from all the entries
      in the death registers for the period between May 1918 and April 1919. The
      Spanish influenza pandemic affected this population sample to a varying extent.
      Depending on the characteristic of the different locations, the mortality rate
      varied between 2.2 and 19.7 per thousand for influenza, and between 7.5 and 25.7
      per thousand for influenza and other diseases of the respiratory system. The
      mortality rate for the total population studied has been calculated to be 6.8 per
      thousand for Spanish influenza and 12.1 per thousand for influenza and other
      diseases of the respiratory system. The first wave of the pandemic (spring 1918)
      was benign like a seasonal influenza. The second wave (autumn 1918) was extremely
      virulent owing to the mutation of the virus in Europe during the summer. This
      article identifies one of the sites, on the border between France and Spain, from
      which the second wave of the Spanish flu spread.

PMID- 18828569
TI  - The plot against cancer: heredity and cancer in German and Dutch medicine, 1933
      1945.
AB  - In the Third Reich hereditarian approaches and their eugenic implications seemed
      to offer possibilities for fundamental progress in the fight against cancer. This
      did not lead to an exclusive emphasis on genetics in theory or practice. The
      concept of a hereditary predisposition for cancer, the Krebs-disposition or
      Krebsbereitschaft, led to flexible multifactor approaches, including proposals
      for both eugenic and social-hygienic measures. These approaches were not typical
      of German medicine alone. In the Netherlands hereditarian approaches did not play
      a central role in the 1930s. They lacked institutional support in a country where
      health policies were characterised by indirect strategies working through
      intermediaries such as general practitioners and home nursing organisations.
      However, potentially the elements for similar anti-cancer policies as in Germany
      were present. The German occupation offered opportunities to develop these
      elements (concepts, institutions, personnel). This development was blocked
      because of the political radicalisation during the war and the German defeat.

PMID- 18828570
TI  - They helped modernize Turkey's medical education and practice: refugees from
      Nazism 1933-1945.
AB  - This paper discusses a dimly lit and largely unknown bit of 20th century history.
      Starting in 1933,Turkey reformed its medical health care system using invitees
      fleeing the Nazis and for whom America was out of reach because of restrictive
      immigration laws and wide-spread anti-Semitic hiring bias at its universities.
      Among the invitees were several medical scholars who played a large role in
      westernizing the new Turkish republic's medical practice and research as well as
      its school curricula.

PMID- 18828571
TI  - [Historiography of the body and medicine in ancient and medieval China: 1997
      2007].

PMID- 18828572
TI  - Nanojets, electrospray, and ion field evaporation: molecular dynamics simulations
      and laboratory experiments.
AB  - The energetics, interfacial properties, instabilities, and fragmentation patterns
      of electrosprays made from formamide salt solutions are investigated in a mass
      spectrometric vacuum electrospray experiment and using molecular dynamics (MD)
      simulations. The electrospray source is operated in a Taylor cone-jet mode, with
      the nanojet that forms being characterized by high surface-normal electric field
      strengths in the vicinity of 1 V/nm. Mass-to-charge ratios were determined for
      both positive and negative currents sprayed from NaI-formamide solutions with
      solute-solvent mole ratios of 1:8.4 and 1:36.9, and from KI-formamide solutions
      with mole ratios of 1:41 and 1:83. The molecular dynamics simulations were
      conducted on isolated 10 nm NaI-formamide droplets at mole ratios of 1:8 and
      1:16. The droplet was subjected to a uniform electric field with strengths
      ranging between 0.5 and 1.5 V/nm. Both the experiments and simulations
      demonstrate a mixed charge emission regime where field-induced desorption of
      solvated ions and charged droplets occurs. The macroscopic parameters, such as
      average mass-to-charge ratio and maximum surface-normal field strengths deduced
      from the simulations are found to be in good agreement with the experimental work
      and consistent with electrohydrodynamic theory of cone-jets. The observed mass
      spectrometric Na (+) and I (-) solvated ion distributions are consistent with a
      thermal evaporation process, and are correctly reproduced by the simulation after
      incorporation of the different flight times and unimolecular ion dissociation
      rates in the analysis. Alignment of formamide dipoles and field-induced
      reorganization of the positive and negative ionic charges in the interfacial
      region are both found to contribute to the surface-normal field near the points
      of charge emission. In the simulations the majority of cluster ions are found to
      be emitted from the tip of the jet rather than from the neck region next to the
      Taylor cone. This finding is consistent with the experimental energy
      distributions of the solvated ions which demonstrate that indeed most ions are
      emitted closer to the jet region, that is, beyond the cone-neck region where
      ohmic losses occur. This observation is also consistent with continuum
      electrohydrodynamic predictions of cluster-ion evaporation at surface regions of
      high curvature and therefore maximum surface electric field strengths, which may
      be the cone-neck region, the breakup region of the jet (usually near the tip of
      the jet), or the emitted charged droplets. In the nanoscale jets observed in this
      study, the regions of highest spatial curvature are at the ends of the jets where
      nascent drops either are forming or have just detached.

PMID- 18828573
TI  - Hunter-killer peptide (HKP) for targeted therapy.

PMID- 18828574
TI  - Electronic and vibrational relaxation of porphycene in solution.
AB  - The relaxation of electronically excited porphycene in acetonitrile solution has
      been studied by transient absorption spectroscopy supported by global analysis
      techniques. Three processes following the femtosecond pulse excitation to the S 2
      state have been identified: the intramolecular vibrational redistribution on the
      time scale of tens of femtoseconds, the internal conversion S 2 right arrow-wavy
      S 1 (750 fs) and thermal equilibration of the molecule by energy exchange with
      the solvent (16 ps). The recorded transient absorption kinetics exhibit
      oscillations which have been assigned to the evolution of wavepackets in both S 1
      and S 0 states.

PMID- 18828575
TI  - Formation and characterization of two FeO3 isomers in solid argon.
AB  - Two FeO 3 isomers were prepared and characterized using matrix isolation infrared
      spectroscopy and theoretical calculations. The iron monoxide molecules produced
      from laser evaporation of the bulk iron oxide target react with dioxygen in solid
      argon to form the (eta (2)-O 2)FeO complex spontaneously on annealing. The (eta
      (2)-O 2)FeO complex was predicted to have a (5)B 2 ground state with a planar C 2
      v structure, in which the O 2 fragment is side-on bonded to the iron center. The
      (eta (2)-O 2)FeO complex rearranges to the more stable iron trioxide isomer upon
      visible light (lambda > 500 nm) irradiation. The iron trioxide molecule was
      predicted to have a closed-shell singlet ground state with a planar D 3 h
      symmetry, in which the iron possesses a +6 oxidation state.

PMID- 18828576
TI  - Computational study of pharmacophores: beta-sultams.
AB  - The strain and resonance energies in beta-sultam derivatives have been calculated
      by using a high-level ab initio method (G3/B3LYP) in order to resolve the
      question of the principal driving force affecting solvolysis of these new
      antibiotics. We found that only the combined effect of stabilizing (via amide or
      sulfonamide resonance interactions) and destabilizing (ring strain) influences
      can account for the observed rates of solvolysis in beta-lactams and beta
      sultams.

PMID- 18828577
TI  - On the construction of diabatic and adiabatic potential energy surfaces based on
      ab initio valence bond theory.
AB  - A theoretical model is presented for deriving effective diabatic states based on
      ab initio valence bond self-consistent field (VBSCF) theory by reducing the
      multiconfigurational VB Hamiltonian into an effective two-state model. We
      describe two computational approaches for the optimization of the effective
      diabatic configurations, resulting in two ways of interpreting such effective
      diabatic states. In the variational diabatic configuration (VDC) method, the
      energies of the diabatic states are variationally minimized. In the consistent
      diabatic configuration (CDC) method, both the configuration coefficients and
      orbital coefficients are simultaneously optimized to minimize the adiabatic
      ground-state energy in VBSCF calculations. In addition, we describe a mixed
      molecular orbital and valence bond (MOVB) approach to construct the CDC diabatic
      and adiabatic states for a chemical reaction. Note that the VDC-MOVB method has
      been described previously. Employing the symmetric S(N)2 reaction between NH(3)
      and CH(3)NH(3)(+) as a test system, we found that the results from ab initio
      VBSCF and from ab initio MOVB calculations using the same basis set are in good
      agreement, suggesting that the computationally efficient MOVB method is a
      reasonable model for VB simulations of condensed phase reactions. The results
      indicate that CDC and VDC diabatic states converge, respectively, to covalent and
      ionic states as the molecular geometries are distorted from the minimum of the
      respective diabatic state along the reaction coordinate. Furthermore, the
      resonance energy that stabilizes the energy of crossing between the two diabatic
      states, resulting in the transition state of the adiabatic ground-state reaction,
      has a strong dependence on the overlap integral between the two diabatic states
      and is a function of both the exchange integral and the total diabatic ground
      state energy.

PMID- 18828578
TI  - Interactions in large, polyaromatic hydrocarbon dimers: application of density
      functional theory with dispersion corrections.
AB  - The interactions within two models for graphene, coronene and hexabenzocoronene
      (HBC), and (H 3C(CH 2) 5) 6-HBC, a synthesizable model for asphaltenes, were
      studied using density functional theory (DFT) with dispersion corrections. The
      corrections were implemented using carbon atom-centered effective core-type
      potentials that were designed to correct the erroneous long-range behavior of
      several DFT methods. The potentials can be used with any computational chemistry
      program package that can handle standard effective core potential input, without
      the need for software modification. Testing on a set of common noncovalently
      bonded dimers shows that the potentials improve calculated binding energies by
      factors of 2-3 over those obtained without the potentials. Binding energies are
      predicted to within ca. 15%, and monomer separations to within ca. 0.1 A, of high
      level wave function data. The application of the present approach predicts
      binding energies and structures of the coronene dimer that are in excellent
      agreement with the results of other DFT methods in which dispersion is taken into
      account. Dimers of HBC show extensive binding in pi-stacking arrangements, with
      the largest binding energy, 44.8 kcal/mol, obtained for a parallel-displaced
      structure. This structure is inline with the published crystal structure.
      Conformations in which the monomers are perpendicular to one another are much
      more weakly bound and have binding energies less than 10 kcal/mol. For dimers of
      (H 3C(CH 2) 5) 6-HBC, which contain 336 atoms, we find that a slipped-parallel
      structure with C s symmetry has a binding energy of 52.4 kcal/mol, 8.9 kcal/mol
      lower than that of a bowl-like, C 6 v -symmetric structure.

PMID- 18828579
TI  - Interactions of mono- and divalent metal ions with aspartic and glutamic acid
      investigated with IR photodissociation spectroscopy and theory.
AB  - The interaction of metal ions with aspartic (Asp) and glutamic (Glu) acid and the
      role of gas-phase acidity on zwitterionic stability were investigated using
      infrared photodissociation spectroscopy in the spectral range 950-1900 cm (-1)
      and by hybrid density functional theory. Lithium ions interact with both carbonyl
      oxygen atoms and the amine nitrogen for both amino acids, whereas cesium
      interacts with both of the oxygen atoms of the C-terminus and the carbonyl oxygen
      of the side chain for Asp. For Glu, this structure is competitive, but a
      structure in which the cesium ion interacts with just the carbonyl oxygen atoms
      is favored and the calculated spectrum for this structure is more consistent with
      the experimentally measured spectrum. In complexes with either of these metal
      ions, both amino acids are non-zwitterionic. In contrast, Glu*Ca (2+) and Glu*Ba
      (2+) both adopt structures in which Glu is zwitterionic and the metal ion
      interacts with both oxygens of the C-terminal carboxylate and the carbonyl oxygen
      in the side chain. Assignment of the zwitterionic form of Glu is strengthened by
      comparisons to the spectrum of the protonated form, which indicate spectral
      features associated with a protonated amino nitrogen. Comparisons with results
      for glutamine, which adopts nearly the same structures with these metal ions,
      indicate that the lower Delta H acid of Asp and Glu relative to other amino acids
      does not result in greater relative stability of the zwitterionic form, a result
      that is directly attributed to effects of the metal ions which disrupt the strong
      interaction between the carboxylic acid groups in the isolated, deprotonated
      forms of these amino acids.

PMID- 18828580
TI  - An experimental and kinetic modeling study of the oxidation of the four isomers
      of butanol.
AB  - Butanol, an alcohol which can be produced from biomass sources, has received
      recent interest as an alternative to gasoline for use in spark ignition engines
      and as a possible blending compound with fossil diesel or biodiesel. Therefore,
      the autoignition of the four isomers of butanol (1-butanol, 2-butanol, iso
      butanol, and tert-butanol) has been experimentally studied at high temperatures
      in a shock tube, and a kinetic mechanism for description of their high
      temperature oxidation has been developed. Ignition delay times for
      butanol/oxygen/argon mixtures have been measured behind reflected shock waves at
      temperatures and pressures ranging from approximately 1200 to 1800 K and 1 to 4
      bar. Electronically excited OH emission and pressure measurements were used to
      determine ignition-delay times. The influence of temperature, pressure, and
      mixture composition on ignition delay has been characterized. A detailed kinetic
      mechanism has been developed to describe the oxidation of the butanol isomers and
      validated by comparison to the shock-tube measurements. Reaction flux and
      sensitivity analysis illustrates the relative importance of the three competing
      classes of consumption reactions during the oxidation of the four butanol
      isomers: dehydration, unimolecular decomposition, and H-atom abstraction. Kinetic
      modeling indicates that the consumption of 1-butanol and iso-butanol, the most
      reactive isomers, takes place primarily by H-atom abstraction resulting in the
      formation of radicals, the decomposition of which yields highly reactive
      branching agents, H atoms and OH radicals. Conversely, the consumption of tert
      butanol and 2-butanol, the least reactive isomers, takes place primarily via
      dehydration, resulting in the formation of alkenes, which lead to resonance
      stabilized radicals with very low reactivity. To our knowledge, the ignition
      delay measurements and oxidation mechanism presented here for 2-butanol, iso
      butanol, and tert-butanol are the first of their kind.

PMID- 18828581
TI  - Calculating chemically accurate redox potentials for engineered flavoproteins
      from classical molecular dynamics free energy simulations.
AB  - The tricyclic isoalloxazine nucleus of the redox cofactors flavin mononucleotide
      (FMN) and flavin adenine dinucleotide (FAD) acts as an electron sink in life
      sustaining biological electron transfer (eT). The functional diversity of flavin
      containing proteins (flavoproteins) transcends that of free flavins. A large body
      of experimental evidence attributes natural control of flavoprotein-mediated eT
      to tuning of the thermodynamic driving force by the protein environment.
      Understanding and engineering such modulation by the protein environment of the
      flavin redox potential (DeltaE(o)) is valuable in biotechnology and device
      design. In this study we employed classical molecular dynamics free energy
      simulations (MDFES), within a thermodynamic integration (TI) formalism, to
      calculate the change in FMN first reduction potential (DeltaDeltaE(o)(ox/sq))
      imparted by 6 flavoprotein active site mutations. The combined performance of the
      AMBER ff03 (protein) and GAFF (cofactor) force fields was benchmarked against
      experimental data for mutations close to the isoalloxazine re- and si-faces that
      perturb the wild-type DeltaE(o)(ox/sq) value in Anabaena flavodoxin. The
      classical alchemical approach used in this study overestimates the magnitude of
      DeltaE(o) values, in common with other studies. Nevertheless, chemically accurate
      DeltaDeltaE(o) values--calculated to within 1 kcal mol(-1) of the experimental
      value--were obtained for five of the six mutations studied. We have shown that
      this approach is practical for quantitative in silico screening of the effect of
      mutations on the first reduction potential where experimental values and
      structural data are available for the wild-type flavoprotein. This approach
      promises to be useful as an integral part of future interdisciplinary strategies
      to engineer desired thermodynamic properties in flavoproteins of biotechnological
      interest.

PMID- 18828582
TI  - Dissociative photoionization mechanism of 1,8-dihydroxyanthraquinone: an
      experimental and theoretical study.
AB  - The photoionization and dissociative photoionization mechanism of 1,8
      dihydroxyanthraquinone (1,8-DHAQ) have been investigated by infrared laser
      desorption/tunable synchrotron vacuum ultraviolet photoionization mass
      spectrometry (IR LD/VUV PIMS) technique and theoretical calculations. Consecutive
      losses of two carbon monoxides and elimination of hydroxyl group are found to be
      the major fragmentation channels in low photon energy range. Photoionization
      efficiency (PIE) spectrum of 1,8-DHAQ was measured in the photon energy range of
      8.2-15.0 eV. Adiabatic ionization energy (IE) of 1,8-DAHQ (M) and appearance
      energies (AEs) of the major fragments (M-CO) (+), (M-C 2O 2) (+), and (M-OH) (+)
      are determined to be 8.54 +/- 0.05, 10.8 +/- 0.1, 11.0 +/- 0.1, and 13.1 +/- 0.1
      eV, respectively, which are in fair agreement with calculated results. The B3LYP
      method with the 6-31+G(d) basis set was used to study fragmentation of 1,8-DHAQ.
      Theoretical calculations indicate that five lowest-energy isomers of 1,8-DHAQ
      cations can coexist by virtue of bond rotation and intramolecular proton
      transfer. A number of decarbonylation and dehydroxylation processes of 1,8-DHAQ
      cations are well established.

PMID- 18828583
TI  - Small molecule modulators of toll-like receptors.

PMID- 18828584
TI  - Organization of tetrahedral chalcogenide clusters using a tetrahedral
      quadridentate linker.
AB  - Using predesigned tetrahedral quadridentate linker tetrakis(4
      pyridyloxymethylene)methane (TPOM) as the organic linker, tetrahedral P1 clusters
      ([Cd8S(SPh)16](2-)) and C1 clusters ([Cd17S4(SPh)28](2-)) have been assembled
      into beltlike (MCOF-9) or chainlike (MCOF-10) configurations, as determined by
      single-crystal X-ray diffraction. The onset of optical absorptions of MCOF-9 and
      MCOF-10 is around 400 and 420 nm, respectively. The thermal analysis shows that
      both materials are stable up to 250 degrees C.

PMID- 18828585
TI  - Turn-on fluorescence detection of H2O2 and TATP.
AB  - Peroxide-based explosives, like triacetone triperoxide (TATP), are important
      targets for detection because of their broad use in improvised explosives but
      pose challenges. We report a highly sensitive turn-on fluorescence detection for
      H2O2 and organic peroxides, including TATP. The detection strategy relies on
      oxidative deboronation to unmask H2Salen, which subsequently binds Zn(2+) to form
      fluorescent Zn(Salen). Sensitivity is excellent, with detection limits below 10
      nM for H2O2, TATP, and benzoyl peroxide. In addition, acid treatment is necessary
      to sense TATP, suggesting the potential to discriminate between H2O2 and TATP
      based upon minimal sample pretreatment.

PMID- 18828586
TI  - Synthesis, reactivity, and characterization of sodium and rare-earth metal
      complexes bearing a dianionic N-aryloxo-functionalized beta-ketoiminate ligand.
AB  - The synthesis and reactivity of a series of sodium and rare-earth metal complexes
      stabilized by a dianionic N-aryloxo-functionalized beta-ketoiminate ligand were
      presented. The reaction of acetylacetone with 1 equiv of 2-amino-4-methylphenol
      in absolute ethanol gave the compound 4-(2-hydroxy-5-methylphenyl)imino-2
      pentanone (LH2, 1) in high yield. Compound 1 reacted with excess NaH to afford
      the novel sodium cluster [LNa2(THF)2]4 (2) in good isolated yield. Structure
      determination revealed that complex 2 has the 22-vertex cage structure. Reactions
      of complex 2 with anhydrous LnCl3 in a 1:4 molar ratio, after workup, gave the
      desired lanthanide chlorides [LLnCl(DME)]2 [Ln = Y (3), Yb (4), Tb (5)] as
      dimers. A further study revealed that complexes 3-5 are inert for chlorine
      substitution reactions. (ArO)3Ln(THF) (ArO = 2,6-Bu(t)2-4-MeC6H2O) reacted with
      compound 1 in a 1:1 molar ratio in tetrahydrofuran (THF), after workup, to give
      the desired rare-earth metal aryloxides as dimers [LLn(OAr)(THF)]2 [Ln = Nd (6),
      Sm (7), Yb (8), Y (9)] in high isolated yields. All of these complexes are well
      characterized, and the definitive molecular structures of complexes 2 and 4-6
      were determined. It was found that complexes 6-9 can be used as efficient
      initiators for L-lactide polymerization, and the ionic radii of the central
      metals have a significant effect on the catalytic activity.

PMID- 18828587
TI  - Crystallographic, electrochemical, and electronic structure studies of the
      mononuclear complexes of Au(I)/(II)/(III) with [9]aneS2O ([9]aneS2O = 1-oxa-4,7
      dithiacyclononane).
AB  - The mononuclear macrocyclic complexes [Au(I)([9]aneS2O)2]BF4 x MeCN 1a,
      [Au(II)([9]aneS2O)2](BF4)2 x 2 MeCN 2a, and
      [Au(III)([9]aneS2O)2](ClO4)6(H5O2)(H3O)2 3 ([9]aneS2O = 1-oxa-4,7
      dithiacyclononane) have been prepared and structurally characterized by single
      crystal X-ray crystallography. The oxidation of [Au([9]aneS2O)2](+) to
      [Au([9]aneS2O)2](2+) involves a significant reorganization of the co-ordination
      sphere from a distorted tetrahedral geometry in [Au([9]aneS2O)2](+) [Au-S
      2.3363(12), 2.3877(12), 2.6630(11), 2.7597(13) A] to a distorted square-planar co
      ordination geometry in [Au([9]aneS2O)2](2+). The O-donors in [Au([9]aneS2O)2](2+)
      occupy the axial positions about the Au(II) center [Au...O = 2.718(2) A] with the
      S-donors occupying the equatorial plane [Au-S 2.428(8) and 2.484(8) A].
      [Au([9]aneS2O)2](3+) shows a co-ordination sphere similar to that of
      [Au([9]aneS2O)2](2+) but with significantly shorter axial Au...O interactions
      [2.688(2) A] and equatorial Au-S bond lengths [2.340(4) and 2.355(6) A]. The
      cyclic voltammogram of 1 in MeCN (0.2 M NBu4PF6, 253 K) at a scan rate of 100 mV
      s(-1) shows an oxidation process at E(p)(a) = +0.74 V and a reduction process at
      E(p)(c) = +0.41 V versus Fc(+)/Fc assigned to the two-electron Au(III/I) couple
      and a second reduction process at E(p)(c) = +0.19 V assigned to the Au(I/0)
      couple. This electrochemical assignment is confirmed by coulometric and UV-vis
      spectroelectrochemical measurements. Multifrequency EPR studies of the
      mononuclear Au(II) complex [Au([9]aneS2O)2](2+) in a fluid solution at X-band and
      as frozen solutions at L-, S-, X-, K-, and Q-band reveal g(iso) = 2.0182 and
      A(iso) = -44 x 10(-4) cm(-1); g(xx) = 2.010, g(yy) = 2.006, g(zz) = 2.037; A(xx)
      = -47 x 10(-4) cm(-1), A(yy) = -47 x 10(-4) cm(-1), A(zz) = -47 x 10(-4) cm(-1);
      P(xx) = -18 x 10(-4) cm(-1), P(yy) = -10 x 10(-4) cm(-1), and P(zz) = 28 x 10(-4)
      cm(-1). DFT calculations predict a singly occupied molecular orbital (SOMO) with
      27.2% Au 5d(xy) character, consistent with the upper limit derived from the
      uncertainties in the (197)Au hyperfine parameters. Comparison with
      [Au([9]aneS3)2](2+) reveals that the nuclear quadrupole parameters, P(ii) (i = x,
      y, z) are very sensitive to the nature of the Au(II) co-ordination sphere in
      these macrocyclic complexes. The observed geometries and bond lengths for the
      cations [Au([9]aneS2O)2](+/2+/3+) reflect the preferred stereochemistries of
      d(10), d(9), and d(8) metal ions, respectively, with the higher oxidation state
      centers being generated at higher anodic potentials compared to the related
      complexes [Au([9]aneS3)2](+/2+/3+).

PMID- 18828588
TI  - Probing the solvent dependent photophysics of fac-[Re(CO)3(dppz-X2)Cl] (dppz-X2 =
      11,12-X2-dipyrido[3,2-a:2',3'-c]phenazine); X = CH3, H, F, Cl, CF3).
AB  - The results of electrochemical measurements, density-functional theory
      calculations, emission and time-resolved IR (TRIR) spectroscopic studies for fac
      [ReCl(CO)3(dppz-X2)], (dppz = dipyrido[3,2-a:2',3'-c]phenazine; X = CH3, H, F,
      Cl, CF3) are reported. For all complexes the calculations show that the lowest
      unoccupied molecular orbital (LUMO) is a phenazine based orbital localized on the
      dppz ligand. We observe that three different excited states, IL pi pi*, metal-to
      ligand charge-transfer (MLCT) (phen), and MLCT (phz), are formed depending upon
      the substituent on the dppz ligand and on the nature of the solvent. This means
      that both the energy and the nature of the photophysically active state(s) can be
      tuned by both chemical modification of dppz ligand and solvent properties. The
      excited-state dynamics in these systems is directly related to the mechanism of
      the "light switch effect", and ps-TRIR has allowed a deeper insight into this
      mechanism by being able to directly monitor the change in the population of the
      higher lying emissive phen-type (3)MLCT and IL pi pi* states and the dark (3)MLCT
      (phz) state depending on the different environmental factors.

PMID- 18828589
TI  - Tandem action of the O2- and FADH2-dependent halogenases KtzQ and KtzR produce
      6,7-dichlorotryptophan for kutzneride assembly.
AB  - Kutznerides are actinomycete-derived antifungal nonribosomal hexadepsipeptides
      which are assembled from five unsual nonproteinogenic amino acids and one hydroxy
      acid. Conserved in all structurally characterized kutznerides is a dichlorinated
      tricyclic hexahydropyrroloindole postulated to be derived from 6,7
      dichlorotryptophan. In this Communication, we identify KtzQ and KtzR as tandem
      acting FADH2-dependent halogenases that work sequentially on free L-tryptophan to
      generate 6,7-dichloro-L-tryptophan. Kinetic characterization of these two enzymes
      has shown that KtzQ (along with the flavin reductase KtzS) acts first to
      chlorinate at the 7-position of L-tryptophan. KtzR, with a 120 fold preference
      for 7-chloro-L-tryptophan over L-tryptophan, then installs the second chlorine at
      the 6-position of 7-chloro-L-tryptophan to generate 6,7-dichloro-L-tryptophan.
      These findings provide further insights into the enzymatic logic of carbon
      chloride bond formation during the biosynthesis of halogenated secondary
      metabolites.

PMID- 18828590
TI  - Biosynthesis of (-)-(1S,2R)-allocoronamic acyl thioester by an Fe(II)-dependent
      halogenase and a cyclopropane-forming flavoprotein.
AB  - The biosynthetic gene cluster for the kutzneride family of hexapeptidolactones
      includes the four-gene cassette ktzABCD postulated to generate a nonproteinogenic
      amino acid. Encoded by this cassette are the nonheme FeII-dependent halogenase
      KtzD and the acyl-CoA dehydrogenase-like flavoprotein KtzA, proposed to work in
      conjunction with adenylating protein KtzB and carrier protein KtzC. In the
      present work, we report the in vitro reconstitution of this four-protein system
      and identify the final product as (1S,2R)-allocoronamic acid bound in thioester
      linkage to KtzC. Further analysis of KtzD and KtzA support a biosynthetic pathway
      that involves KtzD-mediated generation of a gamma-chloroisoleucyl intermediate
      which is cyclized to the final product by KtzA without redox participation of the
      bound flavin cofactor. This work introduces a new monomer for potential
      incorporation into nonribosomal peptides and validates the unique strategy for
      its biosynthesis.

PMID- 18828591
TI  - Highly selective synthesis of the ring-B reduced chlorins by ferric chloride
      mediated oxidation of bacteriochlorins: effects of the fused imide vs isocyclic
      ring on photophysical and electrochemical properties.
AB  - The oxidation of bacteriopyropheophorbide with ferric chloride hexahydrate or its
      anhydrous form produced the ring-D oxidized (ring-B reduced) chlorin in >95%
      yield. Replacing the five-member isocyclic ring in bacteriopyropheophorbide- a
      with a fused six-member N-butylimide ring system made no difference in
      regioselective oxidation, and the corresponding ring-B reduced chlorin was
      isolated in almost quantitative yield. When the oxidant was replaced by 2,3
      dichloro-5,6-dicyano-p-benzoquinone, which is frequently used at the oxidizing
      stage of the porphyrin synthesis, the ring-B oxidized (ring-D reduced) chlorins
      were obtained. With both ring-B reduced and ring-D reduced chlorins in hand,
      their photophysical and electrochemical properties were examined and compared for
      the first time. The ring-B reduced chlorine 20, with a fused six-member N
      butylimide ring, exhibits the most red-shifted absorption band (at lambda(max) =
      746 nm), the lowest fluorescence quantum yield (4.5%), and the largest quantum
      yield of singlet oxygen formation (67%) among the reduced ring-B and ring-D
      chlorins investigated in this study. Measurements of the one-electron oxidation
      and reduction potentials show that compound 20 is also the easiest to oxidize
      among the examined compounds and the third easiest to reduce. In addition, the
      1.62 eV HOMO-LUMO gap of 20 is the smallest of the examined compounds, and this
      agrees with values calculated using the DFT method. Spectroelectrochemical
      measurements afforded UV-visible absorption spectra for both the radical cations
      and radical anions of the examined chlorins. The ring-B reduced compound 20, with
      a fused six-member N-butylimide ring, is regarded as the most promising candidate
      in this study for photodynamic therapy because it has the longest wavelength
      absorption and the largest quantum yield of singlet oxygen formation among the
      compounds investigated.

PMID- 18828592
TI  - Novel and rapid palladium-assisted 6pi electrocyclic reaction affording 9,10
      dihydrophenanthrene and its analogues.
AB  - A novel methodology for the synthesis of 9,10-dihydrophenanthrene and its
      analogues has been developed via a palladium-assisted 6pi electrocyclic reaction
      followed by formaldehyde elimination.

PMID- 18828593
TI  - Catalytic chain-breaking pyridinol antioxidants.
AB  - When assayed for their capacity to inhibit azo-initiated peroxidation of linoleic
      acid in a water/chlorobenzene two-phase system, tellurium-containing 3-pyridinols
      were readily regenerable by N-acetylcysteine contained in the aqueous phase. The
      best inhibitors quenched peroxyl radicals more efficiently than alpha-tocopherol,
      and the duration of inhibition was limited only by the availability of the thiol
      reducing agent. The compounds were also found to catalyze reduction of hydrogen
      peroxide in the presence of thiol reducing agent.

PMID- 18828594
TI  - Palladium-catalyzed conjugate allylation reactions of alpha,beta-unsaturated N
      acylpyrroles.
AB  - Conjugate allylation reactions of alpha,beta-unsaturated N-acylpyrroles using
      allylboronic ester are catalyzed by a palladium complex that is ligated by a
      bidentate N-heterocyclic carbene. A variety of functional groups are tolerated,
      and substrates functionalized with electron-withdrawing groups react to afford
      the highest yields of products. Regioselectivity for 1,4-allylation over 1,2
      allylation is demonstrated, and mechanistic experiments are consistent with
      formation of nucleophilic allylpalladium intermediates.

PMID- 18828595
TI  - Processing and storage effects on orange juice aroma: a review.
AB  - Freshly squeezed orange juice aroma is due to a complex mixture of volatile
      compounds as it lacks a specific character impact compound. Fresh hand-extracted
      juice is unstable, and thermal processing is required to reduce enzyme and
      microbial activity. Heating protocols range from the lightly heated not from
      concentrate, NFC, to the twice heated, reconstituted from concentrate, RFC,
      juices. Thermal processing profoundly effects aroma composition. Aroma volatiles
      are further altered by subsequent time-temperature storage conditions. Heating
      reduces levels of reactive aroma impact compounds such as neral and geranial, and
      creates off-flavors or their precursors from Maillard, Strecker, and acid
      catalyzed hydration reactions. Off-flavors such as 4-vinylguaiacol, p-cymene, and
      carvone are the products of chemical reactions. Other off-flavors such as butane
      2,3-dione, guaiacol, and 2,6-dichlorophenol are indicators of microbial
      contaminations. Since most orange juice consumed worldwide is processed, the goal
      of this review is to summarize the widely scattered reports on orange juice aroma
      differences in the three major juice products and subsequent aroma changes due to
      packaging, storage, and microbial contamination with special emphasis on results
      from GC-O studies.

PMID- 18828596
TI  - New qualitative approach in the characterization of antioxidants in white wines
      by antioxidant free radical scavenging and NMR techniques.
AB  - The aim of this study was to obtain new information on antioxidant compounds in
      white wines. For this purpose, white wine degradation was promoted by a forced
      aged protocol, and six normally aged white wines from different vintages were
      analyzed. Both normal and forced aged wines were sequentially extracted using
      hexane and ethyl acetate. Apolar antioxidants were removed using hexane, and
      polar antioxidants were extracted with ethyl acetate. This last residue was
      subject to partial re-extraction with hexane and acetone. The antioxidant
      capacity of the wines and of each fraction was evaluated by two free radical
      methods, ABTS and DPPH. Normal aging provides a decrease in the total antioxidant
      capacity of wines. The antioxidant activity of ethyl acetate/acetone extracts was
      approximately 95% higher than that found for the hexane extracts. Concerning the
      forced aged wines, results showed that the wine submitted to a temperature of 60
      degrees C for 21 days had higher antioxidant activity than that submitted to a
      temperature of 20 degrees C. With regard to the ethyl acetate/acetone extracts,
      oxygen and temperature treatment leads to a decrease in their antioxidant
      activity. NMR analysis was performed in the highest antioxidant capacity organic
      fractions (ethyl acetate/acetone extracts) and in the aqueous fraction of the
      control wine (T = 20 degrees C), in order to attempt the characterization of
      species involved in oxygen protection. Possible structures of antioxidant
      compounds in white wines were proposed. Two of these are tyrosol-like structures.
      This molecule is a well-known phenolic compound in wine, and it is reported to
      have antioxidative effects.

PMID- 18828597
TI  - Comparison of physicochemical properties of 7S and 11S globulins from pea, fava
      bean, cowpea, and French bean with those of soybean--French bean 7S globulin
      exhibits excellent properties.
AB  - Legume seeds contain 7S and/or 11S globulins as major storage proteins. The amino
      acid sequences of them from many legumes are similar to each other in the species
      but different from each other, meaning that some of these proteins from some
      crops exhibit excellent functional properties. To demonstrate this, we compared
      protein chemical and functional properties (thermal stability, surface
      hydrophobicity, solubility as a function of pH, and emulsifying properties) of
      these proteins from pea, fava bean, cowpea, and French bean with those of soybean
      as a control at the same conditions. The comparison clearly indicated that the 7S
      globulin of French bean exhibited excellent solubility (100%) at pH 4.2-7.0 even
      at a low ionic strength condition (mu = 0.08) and excellent emulsion stability (a
      little phase separation after 3 days) at pH 7.6 and mu = 0.08, although the
      emulsions from most of the other proteins separated in 1 h. These results
      indicate that our assumption is correct.

PMID- 18828598
TI  - Bead-based mesofluidic system for residue analysis of chloramphenicol.
AB  - A highly selective and sensitive mesofluidic immunoassay system based on
      competitive immunoassay in polydimethylsiloxane (PDMS) channels was developed.
      This immunoassay system was successfully applied to quantificationally detect
      chloramphenicol (CAP) in animal foods. The glass beads (O 250 microm) were amino
      silane modified, covalently precoated with chloramphenicol succinate, and then
      infused into the microchannels (O 300 microm); the CAP molecules of samples or
      standards in flow solution competed for CAP antibody with the CAP immobilized on
      the beads. The CAP antigen-antibody complex anchored on the beads was probed by
      Cy5-labeled secondary antibody, and the fluorescence intensities of beads were
      employed to determine the concentration of CAP. In this system, the detection
      limit of CAP is 0.008 microg/L. The method reveals good recovery rates from 90 to
      108% and coefficients of variance (CV) from 4.72 to 6.52%. The experimental
      results demonstrate that the bead-based mesofluidic system has high sensitivity
      and excellent performance. Indeed, this system can readily be operated
      automatically and expanded for multicomponent analysis. It is therefore an
      attractive alternative to conventional immunoassays in routine supervised domain
      application for contamination in foods or the environment.

PMID- 18828599
TI  - Use of a fractal-like gold nanostructure in surface-enhanced raman spectroscopy
      for detection of selected food contaminants.
AB  - The safety of imported seafood products because of the contamination of
      prohibited substances, including crystal violet (CV) and malachite green (MG),
      raised a great deal of concern in the United States. In this study, a fractal
      like gold nanostructure was developed through a self-assembly process and the
      feasibility of using surface-enhanced Raman spectroscopy (SERS) coupled with this
      nanostructure for detection of CV, MG, and their mixture (1:1) was explored. SERS
      was capable of characterizing and differentiating CV, MG, and their mixture on
      fractal-like gold nanostructures quickly and accurately. The enhancement factor
      of the gold nanostructures could reach an impressive level of approximately 4 x
      10(7), and the lowest detectable concentration for the dye molecules was at
      approximately 0.2 ppb level. These results indicate that SERS coupled with
      fractal-like gold nanostructures holds a great potential as a rapid and ultra
      sensitive method for detecting trace amounts of prohibited substances in
      contaminated food samples.

PMID- 18828600
TI  - Phytochemicals of apple peels: isolation, structure elucidation, and their
      antiproliferative and antioxidant activities.
AB  - Bioactivity-guided fractionation of Red Delicious apple peels was used to
      determine the chemical identity of bioactive constituents, which showed potent
      antiproliferative and antioxidant activities. Twenty-nine compounds, including
      triterpenoids, flavonoids, organic acids and plant sterols, were isolated using
      gradient solvent fractionation, Diaion HP-20, silica gel, and ODS columns, and
      preparative HPLC. Their chemical structures were identified using HR-MS and 1D
      and 2D NMR. Antiproliferative activities of isolated pure compounds against HepG2
      human liver cancer cells and MCF-7 human breast cancer cells were evaluated. On
      the basis of the yields of isolated flavonoids (compounds 18- 23), the major
      flavonoids in apple peels are quercetin-3-O-beta-D-glucopyranoside (compound 20,
      82.6%), then quercetin-3-O-beta-D-galactopyranoside (compound 19, 17.1%),
      followed by trace amounts of quercetin (compound 18, 0.2%), (-)-catechin
      (compound 22), (-)-epicatechin (compound 23), and quercetin-3-O-alpha-L
      arabinofuranoside (compound 21). Among the compounds isolated, quercetin (18) and
      quercetin-3-O-beta-D-glucopyranoside (20) showed potent antiproliferative
      activities against HepG2 and MCF-7 cells, with EC 50 values of 40.9 +/- 1.1 and
      49.2 +/- 4.9 microM to HepG2 cells and 137.5 +/- 2.6 and 23.9 +/- 3.9 microM to
      MCF-7 cells, respectively. Six flavonoids (18-23) and three phenolic compounds
      (10, 11, and 14) showed potent antioxidant activities. Caffeic acid (10),
      quercetin (18), and quercetin-3-O-beta-D-arabinofuranoside (21) showed higher
      antioxidant activity, with EC 50 values of <10 microM. Most tested flavonoids and
      phenolic compounds had high antioxidant activity when compared to ascorbic acid
      and might be responsible for the antioxidant activities of apples. These results
      showed apple peel phytochemicals have potent antioxidant and antiproliferative
      activities.

PMID- 18828601
TI  - Inhibition of gap junctional intercellular communication by the green tea
      polyphenol (-)-epigallocatechin gallate in normal rat liver epithelial cells.
AB  - (-)-Epigallocatechin gallate (EGCG), a polyphenolic compound found in green tea,
      is a promising chemopreventive agent against cancer due to its strong
      antiproliferative effects on cancer cells; however, its possible toxicity and
      carcinogenicity must be investigated before EGCG can be used as a dietary
      supplement for chemoprevention. The inhibition of gap junctional intercellular
      communication (GJIC) is strongly associated with carcinogenesis, particularly the
      tumor promotion process; thus, we investigated the effects of EGCG on GJIC in WB
      F344 normal rat liver epithelial (RLE) cells. EGCG, but not (-)-epicatechin (EC),
      another polyphenol found in green tea, inhibited GJIC in a dose-dependent and
      reversible manner in RLE cells. EGCG also induced the phosphorylation of connexin
      43 (Cx43), a major regulator of GJIC. The phosphorylation of extracellular signal
      regulated protein kinase 1/2 (ERK1/2) was also observed in EGCG-treated RLE
      cells. The inhibition of GJIC and phosphorylation of Cx43 and ERK1/2 by EGCG were
      completely blocked by U0126, a pharmacological inhibitor of mitogen-activated
      protein kinase/ERK kinase. EGCG generated a larger amount of hydrogen peroxide
      than EC in a dose-dependent manner. Furthermore, catalase partially inhibited the
      EGCG-induced inhibition of GJIC and the phosphorylation of Cx43 and ERK1/2. These
      results indicated that EGCG inhibited GJIC mainly due to its prooxidant activity.

PMID- 18828602
TI  - Anthocyanin and ascorbic acid degradation in sonicated strawberry juice.
AB  - Strawberry juice samples were sonicated at amplitude levels ranging from 40 to
      100% at a constant frequency of 20 kHz for treatment times (2-10 min) and pulse
      durations of 5 s on and 5 s off. Sonication was found to reduce anthocyanin and
      ascorbic acid contents by 3.2 and 11%, respectively, at the maximum treatment
      conditions. Response surface methodology (RSM) based on a two-factor, five-level
      central composite design was employed to determine the effect of amplitude level
      and treatment time on anthocyanins (P3G), ascorbic acid (AA) content, and color
      values (L*, a*, and b*). The model predictions for the selected nutritional and
      quality parameters were closely correlated to the experimental results. RSM was
      demonstrated to be an effective technique to model the effect of sonication on
      strawberry juice quality while minimizing the number of experiments required.

PMID- 18828603
TI  - Environmentally friendly formulations of alachlor and atrazine: preparation,
      characterization, and reduced leaching.
AB  - Atrazine and alachlor formulations were designed by encapsulating the herbicide
      molecules into phosphatidylcholine (PC) vesicles, which subsequently were
      adsorbed on montmorillonite. PC and montmorillonite are classified as substances
      of minimal toxicological risk by the U.S. EPA. PC enhanced alachlor and atrazine
      solubilities by 15- and 18-fold, respectively. A 6 mM PC:5 g/L clay ratio was
      found as optimal for PC adsorption on the clay. Active ingredient contents of the
      PC-clay formulations ranged up to 8.6% for atrazine and 39.5% for alachlor.
      Infrared spectroscopy showed hydrophobic interactions of herbicide molecules with
      the alkyl chains of PC, in addition to hydrophilic interactions with the PC
      headgroup. Release experiments in a sandy soil showed a slower rate from the PC
      clay formulations than the commercial ones. Soil column experiments under
      moderate irrigation and bioactivity experiments indicate that a reduction in the
      recommended dose of alachlor and atrazine can be accomplished by using PC-clay
      formulations.

PMID- 18828604
TI  - Effects of caseins on thermal stability of bovine beta-lactoglobulin.
AB  - Casein fractions have been shown to act as molecular chaperones and inhibit
      aggregation of whey proteins in dilute solutions (< or =1% w/v). We evaluated if
      this approach would stabilize protein solutions at higher concentration and
      thermal processing temperatures desired for beverage applications. Mixtures of
      beta-lactoglobulin (BLG) (6% w/v) with either beta-casein (BCN) (0.01-2% w/v) or
      alpha s-casein (ACN) (2% w/v) were adjusted to pH 6.0 and heated (70-90 degrees
      C) for 20 min, cooled, and then analyzed to determine the degree of aggregation.
      Aggregation was determined by solution turbidity as optical density (OD) at 400
      or 600 nm. The addition of 0.05% (w/v) BCN or greater caused a drop in turbidity
      for solutions heated at 70-90 degrees C. In contrast, inhibition was observed in
      BLG-ACN mixtures at 70 degrees C but not at > or =75 degrees C. Moreover,
      prolonged heating (90 min) of BLG with 2% (w/v) BCN (pH 6.0) at 90 degrees C
      produced a clear solution while BLG-ACN solutions formed translucent gels after
      heating for 15 min. The weight-averaged molar mass and root-mean-square (rms)
      radius of soluble aggregates were determined by size exclusion chromatography in
      conjunction with multiangle laser light scattering (SEC-MALS). SEC-MALS confirmed
      the turbidity results by showing that the BLG-BCN mixture (8% w/v protein)
      produced aggregates with lower molar mass and smaller rms radius (majority 20-40
      nm). These results showed that BCN is a feasible component to stabilize higher
      concentrations of whey proteins in beverages.

PMID- 18828605
TI  - Radical scavenging and reducing ability of tilapia (Oreochromis niloticus)
      protein hydrolysates.
AB  - Enzymatically hydrolyzed fish protein hydrolysates could be used as a source of
      antioxidative nutraceuticals. In our current work, we have investigated alkali
      solubilized tilapia ( Oreochromis niloticus) protein hydrolysates for their
      ability to scavenge reactive oxygen species (ROS) and for their reducing power.
      Tilapia protein isolate was prepared by an alkaline solubilization technique and
      used as a substrate for enzyme hydrolysis. Cryotin, protease A 'Amano' 2,
      protease N 'Amano', Neutrase and Flavourzyme, were used separately to determine
      their effectiveness in hydrolyzing tilapia protein isolate. ROS scavenging
      ability was quantified using an isoluminol enhanced chemiluminescent assay in the
      presence of a) hydrogen peroxide or b) mononuclear cells isolated from human
      blood. Ferric reducing antioxidant power (FRAP) and Trolox equivalent antioxidant
      capacity (TEAC) of the hydrolysates using 2, 2'-azinobis-(3-ethylbenzothiazoline
      6-sulfonic acid) or 2,2'-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS),
      were also investigated. Results showed that, in general, the TEAC, FRAP values
      and ROS scavenging ability of the hydrolysates increased with an increase in the
      degree of hydrolysis. Among the different hydrolysates, those prepared using
      Cryotin were most effective and Amano A2 hydrolysates were least effective in
      scavenging ABTS*(+) and ROS generated by hydrogen peroxide. However, FRAP assay
      showed that hydrolysates prepared using Flavourzyme were most effective, and
      Amano N and Neutrase hydrolysates were least effective in reducing ferric ions.
      No significant difference was observed among the hydrolysates produced with
      different enzymes in their ability to scavenge ROS generated by phorbol myristate
      acetate stimulated mononuclear cells. These results shed light on the in vitro
      ROS scavenging ability of alkali solubilized tilapia protein hydrolysates, as
      well as potential nutraceutical use of these hydrolysates.

PMID- 18828606
TI  - Caspase-3 gene silencing for inhibiting apoptosis in insulinoma cells and human
      islets.
AB  - Although islet transplantation has great potential to treat type I diabetes, most
      islet grafts do not function due to the host immune rejection, nonspecific
      inflammatory response and poor revascularization. Since caspase-3 plays a crucial
      role in apoptosis of transplanted islet cells, we used chemically synthesized
      small interfering RNAs (siRNAs) to silence caspase-3 in insulinoma (INS-1E) cells
      and human islets, and then determined whether caspase-3 gene silencing can
      prevent these cells from cytokine-induced apoptosis. Transfection of INS-1E cells
      and islets with siRNAs reduced caspase-3 transcripts by 50-67% and 50%,
      respectively. Additionally, apoptosis in transfected insulinoma cells was
      markedly inhibited. Since gene silencing did not last beyond two days, we
      converted potent siRNA into shRNA and constructed replication deficient
      adenoviral (Adv) vectors encoding these shRNAs driven by a U6 or H1 promoter.
      Compared to chemically synthesized siRNA, Adv-caspase-3-shRNA efficiently
      transduced islets, showed relatively higher and prolonged levels of gene
      silencing beyond five days, with higher gene silencing with a U6 promoter, and
      protected islets from cytokine-induced apoptosis. Finally, return to
      normoglycemia was achieved at 1 day post-transplantation of Adv-caspase-3-shRNA
      transduced islets under the kidney capsules of streptozotocin induced nonobese
      diabetic-severe combined immunodeficiency (NOD-SCID) mice and maintained beyond
      two weeks. Blood glucose levels returned to > or = 325 mg/dL upon removal of the
      islet graft-bearing kidney at 32 days after transplantation, confirming that
      transplanted islets were functional.

PMID- 18828607
TI  - The dawn of dairy.

PMID- 18828608
TI  - Theoretical analysis of secondary structures of beta-peptides.
AB  - Unlike alpha-amino acids, peptides formed from beta-amino acids (beta-peptides)
      display stability toward enzymatic degradation and may form turns and helices
      with as few as four residues. Because both the C alpha and C beta of the beta
      amino acid may bear substituents, a large number of beta-amino acids can be
      synthesized. Beta-peptides form various well-defined secondary structures,
      including 14-helix, 12-helix, 10/12-helix, 10-helix, 8-helix, turn structures,
      sheets, and hairpins. For all of these reasons, beta-amino acids have been
      increasingly used as building blocks for molecular design and pharmaceutical
      applications. To explain the conformational features of beta-peptides, several
      quantum mechanics and molecular dynamics studies that rationalize the observed
      conformational features have been reported. However, a systematic account that
      unifies various factors critical to the conformational features is still lacking.
      In this Account, we present a detailed analysis of the conformational features of
      various beta-peptides. We start by studying the basic local conformational
      features of beta-peptides using di- and tripeptide models. Then, various
      secondary structures of unsubstituted beta-peptides with differing numbers of
      residues are investigated using a repeating unit approach to derive the intrinsic
      backbone conformational features. We find that the 10/12-helix is intrinsically
      most stable for the beta-peptide backbone. The 14-helix, 12-helix, and 10-helix
      structures have similar stabilities for beta-peptide backbones of four to six
      residues. The substituent effects on the stabilities of beta-peptide secondary
      structures are then analyzed. Combined with the substituent effect and the
      intrinsic backbone preferences, all experimental observations of secondary
      structure formation can be understood. For example, the 10/12-helix is favored
      for like-beta(2)/beta(3)-peptides, unlike-beta(3)/beta(3)-peptides, and
      beta(3)/beta-hGly-peptides because these substitution patterns do not cause
      steric problems for the 10/12-helix. Beta(3)-peptides, beta(2)-peptides, and beta
      (2,3)-peptides favor the 14-helix because the substituents in these peptides
      benefit the 14-helix the most but significantly destabilize the 10/12-helix.
      Because the 10/12-helix is intrinsically favored and has two favorable positions
      in each residue for substituents, many more hybrid beta-peptides are predicted to
      exist in this secondary structure, which suggests the need for further
      experiments. These results are valuable for determining the best use of these
      building blocks in the design of well-structured molecules with desirable
      chemical functions.

PMID- 18828609
TI  - Neutron reflectivity study of the complexation of DNA with lipids and surfactants
      at the surface of water.
AB  - Complexation of lipids and surfactants with short DNA fragments at the air-water
      interface has been studied by neutron reflectivity. Complexation with
      zwitterionic lipids occurs in the presence of divalent cations, and ion
      specificity has been demonstrated (binding is less effective with Ba2+ than with
      Mg2+ or Ca2+). One and two DNA layers have been observed for dilute and more
      compact lipid monolayers, respectively. Two DNA layers have also been found with
      the soluble cationic surfactant dodecyltrimethylammonium bromide (DTAB), except
      close to the precipitation boundary. This result is opposite to that found in
      ellipsometry where very thick layers are found in this region. It is possible
      that the ellipsometry signal is due to highly hydrated bulk complexes adsorbing
      at the surface, not seen by neutrons because of unfavorable contrast conditions.
      Long DNA was found to be less keen to form surface complexes than short DNA
      fragments.

PMID- 18828610
TI  - Electrohydrodynamic flow and colloidal patterning near inhomogeneities on
      electrodes.
AB  - Current density inhomogeneities on electrodes (of physical, chemical, or optical
      origin) induce long-range electrohydrodynamic fluid motion directed toward the
      regions of higher current density. Here, we analyze the flow and its implications
      for the orderly arrangement of colloidal particles as effected by this flow on
      patterned electrodes. A scaling analysis indicates that the flow velocity is
      proportional to the product of the applied voltage and the difference in current
      density between adjacent regions on the electrode. Exact analytical solutions for
      the streamlines are derived for the case of a spatially periodic perturbation in
      current density along the electrode. Particularly simple asymptotic expressions
      are obtained in the limits of thin double layers and either large or small
      perturbation wavelengths. Calculations of the streamlines are in good agreement
      with particle velocimetry experiments near a mechanically generated inhomogeneity
      (a "scratch") that generates a current density larger than that of the unmodified
      electrode. We demonstrate that proper placement of scratches on an electrode
      yields desired patterns of colloidal particles.

PMID- 18828611
TI  - Rheological behavior of self-assembling PEG-beta-cyclodextrin/PEG-cholesterol
      hydrogels.
AB  - The rheological properties of a recently developed self-assembling hydrogel
      system composed of beta-cyclodextrin (betaCD)- and cholesterol-derivatized 8-arm
      star-shaped poly(ethylene glycol) (PEG8) were investigated. To understand and
      predict the gel rheological properties, data fitting with the Maxwell model as
      well as comparing the system's concentration-dependent behavior with Cates' model
      for reversibly breaking chains were performed. To investigate the influence of
      the polymer architecture, networks were also prepared by replacing the
      cholesterol-derivatized 8-arm star-shaped PEG by linear bifunctional PEG
      cholesterol or by using 4-arm instead of 8-arm polymers. Rheological analysis
      showed that the 8-arm polymer-based mixtures yielded tight viscoelastic networks,
      but their storage and loss moduli significantly deviated from those predicted by
      the Maxwell model. The scaling of the plateau moduli, relaxation times, and zero
      shear viscosities with concentration for gels composed of 8-arm cholesterol- and
      betaCD-derivatized PEG followed a power law with exponents higher than predicted
      by Cates' model. On the other hand, hydrogels in which linear bifunctional PEG
      cholesterol was used instead of 8-arm star-shaped PEG-cholesterol or which were
      based on 4-arm polymers showed a substantially better fit with the Maxwell model
      and reduced differences between empirical and Cates' theoretical scaling
      exponents. Rheological analysis also showed that the hydrogels were
      thermoreversible. At low temperatures, the gels showed viscoelastic behavior due
      to slow overall relaxation of the polymer chains. At higher temperatures,
      however, a reduced number of betaCD/cholesterol complexes and concomitant faster
      chain relaxation processes eventually led to liquid-like behavior. The
      relationship between temperature and the relaxation time was used to determine an
      activation energy of 46 kJ/mol for breaking and reptation of the polymers.

PMID- 18828612
TI  - Emulsification and stabilization mechanisms of o/w emulsions in the presence of
      chitosan.
AB  - We study emulsification of paraffin oil in aqueous solutions of chitosan without
      adding any other surfactant. By monitoring the surface tension of the water
      paraffin interface, we show that chitosan itself has only a weak surface
      activity. Nevertheless, chitosan dissolved in the aqueous phase allows the
      dispersion of oil by increasing the matrix viscosity and provides stabilization
      of the oil-water interface by forming a dense polyelectrolitic brush on the water
      side of this interface. We characterize emulsions with varying oil content, and
      concentrations of chitosan, and follow their long-term stability. Finally, we
      show that by precipitating the chitosan the rigid elastic network is formed in
      the aqueous phase, making a very stable suspension.

PMID- 18828613
TI  - Spin-assembled nanolayer of a hyperbranched polymer on the anode in organic light
      emitting diodes: the mechanism of hole injection and electron blocking.
AB  - We introduced a spin-assembled nanolayer of hyperbranched poly(ether sulfone)
      with sulfonic acid terminal on top of an indium-tin oxide anode in organic light
      emitting diodes. This results in great improvement in luminous efficiency, better
      than that of devices using a commercially available conducting polymer
      composition as a hole-injection layer. The effect of the nanolayer was
      investigated by impedance spectroscopy, photovoltaic measurement for built-in
      potential, and transient electroluminescence. We concluded that the high luminous
      efficiency resulted from the efficient electron-blocking by the nanolayer and
      hole-injection assisted by the accumulation of electrons at the interface. This
      result implies that, for an efficient hole-injection layer, the electron-blocking
      capability should be incorporated in addition to the hole-injection and 
      transport capability.

PMID- 18828614
TI  - Surface functionalization of silicone rubber for permanent adhesion improvement.
AB  - The surface properties of poly(dimethyl siloxane) (PDMS) layers screen printed
      onto silicon wafers were studied after oxygen and ammonia plasma treatments and
      subsequent grafting of poly(ethylene -alt-maleic anhydride) (PEMA) using X-ray
      photoelectron spectroscopy (XPS), roughness analysis, and contact angle and
      electrokinetic measurements. In the case of oxygen-plasma-treated PDMS, a
      hydrophilic, brittle, silica-like surface layer containing reactive silanol
      groups was obtained. These surfaces indicate a strong tendency for "hydrophobic
      recovery" due to the surface segregation of low-molecular-weight PDMS species.
      The ammonia plasma treatment of PDMS resulted in the generation of amino
      functional surface groups and the formation of a weak boundary layer that could
      be washed off by polar liquids. To avoid the loss of the plasma modification
      effect and to achieve stabilization of the mechanically instable, functionalized
      PDMS top layer, PEMA was subsequently grafted directly or after using gamma-APS
      as a coupling agent on the plasma-activated PDMS surfaces. In this way, long-time
      stable surface functionalization of PDMS was obtained. The reactivity of the PEMA
      coated PDMS surface caused by the availability of anhydride groups could be
      controlled by the number of amino functional surface groups of the PDMS surface
      necessary for the covalent binding of PEMA. The higher the number of amino
      functional surface groups available for the grafting-to procedure, the lower the
      hydrophilicity and hence the lower the reactivity of the PEMA-coated PDMS
      surface. Additionally, pull-off tests were applied to estimate the effect of
      surface modification on the adhesion between the silicone rubber and an epoxy
      resin.

PMID- 18828615
TI  - Formation of annexin-a5 protein/block copolymer micelle complexes: QCM-D and PAGE
      experiments.
AB  - The Annexin-A5 (Anx5) protein is a specific marker of the exposure of
      phosphatidylserine molecules at the surface of cells, which occurs in processes
      such as apoptosis and platelet activation. Decoration of self-assembled block
      copolymer nanostructures by Anx5 is of particular interest in micelle-mediated
      target drug delivery or in vivo magnetic resonance imaging, the Anx5 imparting
      (bio)functionality to the system. In this work, the reversible binding of the
      Anx5 onto polystyrene-b-poly(2-phosphatethyl methacrylate-co-2-hydroxyethyl
      methacrylate) (PS-b-P(PEMA-co-HEMA)) block copolymer micelles in the presence of
      Ca2+ ions is described using Quartz crystal microbalance with dissipation
      monitoring (QCM-D) and polyacrylamide gel electrophoresis (PAGE) analysis. QCM-D
      experiments confirmed the binding process as well as its reversibility and
      dependence on the characteristics of macromolecular assemblies, such as the
      number of phosphonic diacid groups (Pmic) and hydrodynamic diameter (2RH). A
      linear relationship between the amount of micelles and the amount of protein
      bound onto the micelle surface until a saturation point was established by QCM-D.
      The amount of Anx5 bound to PS-b-P(PEMA-co-HEMA) micelles was successfully
      quantified by PAGE experiments in nondenaturing conditions, which also
      corroborated that the binding process is mediated by Ca2+ ions. The ability of
      such surface (bio)-functionalized nanoparticle systems to stabilize and transport
      hydrophobic loads was highlighted by transmission electron microscopy (TEM) of
      assemblies with entrapped iron oxide particles.

PMID- 18828616
TI  - Investigation of a new thermosensitive block copolymer micelle: hydrolysis,
      disruption, and release.
AB  - Thermosensitive polymer micelles are generally obtained with block copolymers in
      which one block exhibits a lower critical solution temperature in aqueous
      solution. We investigate a different design that is based on the use of one block
      bearing a thermally labile side group, whose hydrolysis upon heating shifts the
      hydrophilic-hydrophobic balance toward the destabilization of block copolymer
      micelles. Atom transfer radical polymerization was utilized to synthesize a
      series of diblock copolymers composed of hydrophilic poly(ethylene oxide) (PEO)
      and hydrophobic poly(2-tetrahydropyranyl methacrylate) (PTHPMA). We show that
      micelles of PEO-b-PTHPMA in aqueous solution can be destabilized as a result of
      the thermosensitive hydrolytic cleavage of tetrahydropyranyl (THP) groups that
      transforms PTHPMA into hydrophilic poly(methacrylic acid). The three related
      processes occurring in aqueous solution, namely, hydrolytic cleavage of THP,
      destabilization of micelles, and release of loaded Nile Red (NR), were
      investigated simultaneously using 1H NMR, dynamic light scattering, and
      fluorescence spectroscopy, respectively. At 80 degrees C, the results suggest
      that the three events proceed with a similar kinetics. Although slower than at
      elevated temperatures, the disruption of PEO-b-PTHPMA micelles can take place at
      the body temperature (approximately 37 degrees C), and the release kinetics of NR
      can be adjusted by changing the relative lengths of the two blocks or the pH of
      the solution.

PMID- 18828617
TI  - On the transition between a heterogeneous and homogeneous corona in mixed
      polymeric micelles.
AB  - Two-dimensional NMR and small-angle neutron scattering experiments were performed
      on comicelles of poly(N-methyl-2-vinyl pyridinium iodide)-block-poly(ethylene
      oxide), P2MVP-b-PEO, and poly(acrylic acid)-block-poly(acryl amide), PAA-b-PAAm,
      in aqueous solutions to study whether a transition between a heterogeneous (Janus
      type) and homogeneous corona can be observed upon a variation of parameters that
      are anticipated to affect the miscibility of the PEO and PAAm coronal blocks.
      Investigated were the effect of a salt-induced decrease in micellar aggregation
      number, P agg for 1<or=[NaNO3]<or=279 mM, a temperature increase for
      25<or=T<or=80 degrees C, a variation of the fraction of EO monomers in the
      corona, fEO, at a fixed corona block length, N corona, for 0<or=fEO<or=1, a
      decrease in the PEO block length, N PEO, at a fixed PAAm block length, NPAAm, for
      200<or=NPEO<or=450, and finally, upon a decrease in corona block length at
      NPAAm=NPEO for 100<or=N corona<or=400. These parameters should affect the
      mixing/demixing transition via their effect on the PEO/PAAm interfacial area
      (e.g., as in the case of f EO and P agg) or the relevant Flory-Huggins
      interaction parameters (e.g., as in the case of temperature). None of the above
      parameters was shown to yield a transition toward a homogeneous corona wherein
      the polymer chains are randomly mixed; i.e., the segregation of PAAm and PEO
      chains within the micellar corona of comicelles of PAA-b-PAAm and P2MVP-b-PEO
      appears to be rather robust.

PMID- 18828618
TI  - Mesoporous zirconium titanium oxides. Part 2: Synthesis, porosity, and adsorption
      properties of beads.
AB  - Mesoporous zirconium titanium mixed-oxide beads having disordered wormhole
      textures and mole fractions of Zr (x) ranging from x=0.25 to 0.67 have been
      prepared. The bead preparation method combined the forced hydrolysis of mixtures
      of zirconium-titanium alkoxides in the presence of long-chain carboxylates with
      external gelation. Uniformly sized beads could be produced in the size range 0.5
      1.1 mm by varying the droplet size and viscosity of the mixed-oxide sol, thus
      making them suitable for large-scale column chromatographic applications. The
      beads exhibited narrow pore size distributions with similar mean pore diameters
      of around 3.7 nm. The specific surface areas of the beads were linked to the Zr
      mole fraction in the precursor solution and were generally greater than 350 m2/g
      for x=0.5. A combination of scanning transmission electron microscopy and X-ray
      absorption fine structure analysis indicated that the pore walls of the beads
      were composed of atomically dispersed Zr and Ti to form a continuous network of
      Zr-O-Ti bonds. Mass transport in the beads was evaluated by monitoring the
      kinetics of vanadate and vanadyl adsorption at pH 10.5 and 0.87, respectively.

PMID- 18828619
TI  - Mesoporous zirconium titanium oxides. Part 1: Porosity modulation and adsorption
      properties of xerogels.
AB  - A series of zirconium titanium oxide mesophases containing 33 atom % Zr have been
      prepared using carboxylic acids of different alkyl chain lengths (Cy ) from y=4
      18 through organic-inorganic polymer phase segregation as the gel transition is
      approached. Thermal treatment of these transparent gels up to 450 degrees C
      eliminated the organic template, and domain coarsening occurred affording stable
      worm-hole mesoporous materials of homogeneous composition and pore diameters
      varying from about 3 to 4 nm in fine increments. With such materials, it was
      subsequently possible to precisely study the adsorption of vanadium oxo-anions
      and cations from aqueous solutions and, more particularly, probe the kinetics of
      intraparticle mass transport as a function of the associated pore dimension. The
      kinetics of mass transport through the pore systems was investigated using
      aqueous vanadyl (VO2+) and orthovanadate (VO3(OH)2-) probe species at
      concentrations ranging from 10 to 200 ppm (0.2 to 4 mmol/L) and pH values of 0
      and 10.5, respectively. In the case of both of these vanadium species, the
      zirconium titanate mesophases displayed relatively slow kinetics, taking in
      excess of about 500 min to achieve maximum uptake. By using a pseudo-second-order
      rate law, it was possible to extract the instantaneous and overall rate of the
      adsorption processes and then relate these to the pore diameters. Both the
      instantaneous and overall rates of adsorption increased with increasing surface
      area and pore diameter over the studied pore size range. However, the equilibrium
      adsorption capacity increased linearly with pore diameter only for the higher
      concentrations and was independent of pore diameter for the lower concentration.
      These results have been interpreted using a model in which discrete adsorption
      occurs at low concentrations and is then followed by multilayer adsorption at
      higher concentration.

PMID- 18828620
TI  - Diffusion of macromolecules on lipid vesicles.
AB  - Diffusion of macromolecules on a surface of lipid vesicles of different reduced
      volume and geometry is investigated. It is assumed that the macromolecules deform
      the surface of the vesicles by inducing the spontaneous curvature which is
      proportional to their concentration. We study how nonuniform distribution of
      macromolecules is reflected in the shape of the vesicles and how the shape of the
      vesicles influences the diffusion process.

PMID- 18828621
TI  - Mixed Co/Fe oxide nanoparticles in block copolymer micelles.
AB  - Small iron oxide and Co-doped iron oxide nanoparticles (NPs) were synthesized in
      a commercial amphiphilic block copolymer, poly(ethylene oxide)-b-poly(methacrylic
      acid) (PEO 68-b-PMAA8), in aqueous solutions. The structure and composition of
      the micelles containing guest molecules (metal salts) or NPs (metal oxides) were
      studied using transmission electron microscopy, dynamic light scattering, X-ray
      photoelectron spectroscopy, and X-ray powder diffraction. The enlarged micelle
      cores after incorporation of metal salts are believed to be formed by both PMAA
      blocks containing metal species and penetrating PEO chains. The nanoparticle size
      distributions in PEO 68-b-PMAA8 were determined using small-angle X-ray
      scattering (SAXS) in bulk. Two independent methods for SAXS data interpretation
      for comprehensive analysis of volume distributions of metal oxide NPs showed
      presence of both small particles and larger entities containing metal species
      which are ascribed to organization of block copolymer micelles in bulk. The
      magnetometry measurements revealed that the NPs are superparamagnetic and their
      characteristics depend on the method of the NP synthesis. The important advantage
      of the PEO 68-b-PMAA8 stabilized magnetic nanoparticles described in this paper
      is their remarkable solubility and stability in water and buffers.

PMID- 18828622
TI  - Structural and phase properties of tetracosane (C24H50) monolayers adsorbed on
      graphite: an explicit hydrogen molecular dynamics study.
AB  - We discuss molecular dynamics (MD) computer simulations of a tetracosane (C24H50)
      monolayer physisorbed onto the basal plane of graphite. The adlayer molecules are
      simulated with explicit hydrogens, and the graphite substrate is represented as
      an all-atom structure having six graphene layers. The tetracosane dynamics
      modeled in the fully atomistic manner agree well with experiment. The low
      temperature ordered solid organizes into a rectangularly centered structure that
      is not commensurate with underlying graphite. Above T=200 K, as the molecules
      start to lose their translational and orientational order via gauche defect
      formation a weak smectic mesophase (observed experimentally but never reproduced
      in united atom (UA) simulations) appears. The phase behavior of the adsorbed
      layer is critically sensitive to the way the electrostatic interactions are
      included in the model. If the electrostatic charges are set to zero (as for a UA
      force field), then the melting temperature increases by approximately 70 K with
      respect to the experimental value. When the nonbonded 1-4 interaction is not
      scaled, the melting temperature decreases by approximately 90 K. If the scaling
      factor is set to 0.5, then melting occurs at T=350 K, in very good agreement with
      experimental data.

PMID- 18828623
TI  - Gold nanoparticle deposition using CO2 expanded liquids: effect of pressure
      oscillation and surface-particle interactions.
AB  - Postsynthesis processing of nanoparticles to obtain mesoscale hierarchal
      nanostructures is the key for the development of nanotechnology and smart
      composites/coatings from these materials. We have utilized gas-expanded liquid
      deposition of alkyl-coated gold nanoparticles to study the effects of variable
      process flowrates, variable flow oscillation and variable interaction potential
      of the substrate on nanoparticle array quality. Array quality is measured here as
      completeness of area surface coverage of approximately a monolayer of
      nanoparticles. Quantitative values for surface coverage are averages obtained
      from multiple TEM photomicrographs using Image J digital analysis. The process
      was modified using higher CO2 addition rate outside of the pressure range
      necessary for deposition, and this modified process produced an excellent film
      quality while reducing overall processing time by 45%. The effects of pressure
      oscillation during deposition appeared to anneal the film at the lower flow
      rates, 0.5 and 1.0 mL/min, but a reduction in area coverage was observed with
      pressure oscillation at 3.0 mL/min. Pressure oscillation has emerged as a useful
      tool for researchers to tune the film uniformity and therefore the surface
      roughness. Calculations based on Hamaker theories for surface-particle
      interactions on various substrates were performed, and better surface coverage
      was predicted for C-based surfaces compared to Si3N4 and SiO2 surfaces. Indeed,
      experimental studies verified this general ordering, indicating that if surface
      interactions with the particles are strong deposition directly on the surface
      rather than on pre-existing nanoparticle islands may govern uniform deposition.

PMID- 18828624
TI  - Mechanism of silver ion reduction in concentrated solutions of amphiphilic
      invertible polyesters in nonpolar solvent at room temperature.
AB  - Fast formation and efficient stabilization of silver nanoparticles from
      [Ag(NH3)2]OH are achieved in concentrated nonpolar solutions of amphiphilic
      invertible polyesters based on poly(ethylene oxide) (PEO) and aliphatic
      dicarboxylic acids. Surface-modified silver nanoparticles able to be dispersed in
      both a polar and nonpolar medium are developed in the form of a ready-to-use
      colloidal solution with an enhanced silver concentration. The PEO fragments of
      polyesters form cavities (also called pseudo-crown ester structures) that can
      bind metal ions. The reduction of bound metal ions proceeds via oxidation of
      polyoxyethylene fragments. No chemical reducing agents are necessary in this
      approach. The polyesters act simultaneously as an efficient reducing agent and
      stabilizer. The main focus of the present research is to clarify the chemical
      mechanism of silver ion reduction in amphiphilic polyester solutions. A one
      electron reduction mechanism is proposed to explain the formation of silver
      nanoparticles. The effect of the poly(ethylene oxide) fragment length and the
      polyester concentration are explored by examining several amphiphilic polyesters.

PMID- 18828625
TI  - Transcriptomic and metabonomic profiling of obesity-prone and obesity-resistant
      rats under high fat diet.
AB  - Rodents respond to chronic high fat diet in at least two ways: some of them may
      readily gain body weight and become obese (termed obesity-prone, OP), and others
      may not (termed obesity-resistant, OR). Transcriptomic and metabonomic profiling
      of OP and OR rats has been conducted, showing two sets of significantly different
      phenotypic profiles in response to 16 weeks of high fat diet. We observed
      significant differences in transcriptional expression of nearly 80 genes, some of
      which are known to be involved in lipid metabolism, transport, and ketone body
      production. The different metabolic profiles in liver tissue extracts, serum, and
      urine between the two phenotypes can be ascribed to the corresponding pathways
      identified with multivariate statistical analysis, including fatty acid
      metabolism, Krebs cycle, and amino acid metabolism. The integration of results
      from transcriptomic and metabonomic studies revealed that the altered metabolic
      pathways in OP rats may involve the increased activity of sympathetic nervous
      system and Krebs cycle, an increased production of ketone bodies, and an adaptive
      regulatory process to store excessive lipids in liver through reverse cholesterol
      transport process. These biochemical variations at transcriptional and metabolic
      levels as a result of dietary intervention highlight the significance of combined
      "omics" strategy in the mechanistic study of obesity and metabolic disorders.

PMID- 18828626
TI  - Distinction between human cytochrome P450 (CYP) isoforms and identification of
      new phosphorylation sites by mass spectrometry.
AB  - In mammals, Cytochrome P450 (CYP) enzymes are bound to membranes of the
      endoplasmic reticulum and mitochondria, where they are responsible for the
      oxidative metabolism of many xenobiotics as well as organic endogenous compounds.
      In humans, 57 isoforms were identified which are classified based on sequence
      homology. In the present work, we demonstrate the performance of a mass
      spectrometry-based strategy to simultaneously detect and differentiate distinct
      human Cytochrome P450 (CYP) isoforms including the highly similar CYP3A4, CYP3A5,
      CYP3A7, as well as CYP2C8, CYP2C9, CYP2C18, CYP2C19, and CYP4F2, CYP4F3, CYP4F11,
      CYP4F12. Compared to commonly used immunodetection methods, mass spectrometry
      overcomes limitations such as low antibody specificity and offers high
      multiplexing possibilities. Furthermore, CYP phosphorylation, which may affect
      various biochemical and enzymatic properties of these enzymes, is still poorly
      analyzed, especially in human tissues. Using titanium dioxide resin combined with
      tandem mass spectrometry for phosphopeptide enrichment and sequencing, we
      discovered eight human P450 phosphorylation sites, seven of which were novel. The
      data from surgical human liver samples establish that the isoforms CYP1A2,
      CYP2A6, CYP2B6, CYP2E1, CYP2C8, CYP2D6, CYP3A4, CYP3A7, and CYP8B1 are
      phosphorylated in vivo. These results will aid in further investigation of the
      functional significance of protein phosphorylation for this important group of
      enzymes.

PMID- 18828627
TI  - A comparative study of electrostatic repulsion-hydrophilic interaction
      chromatography (ERLIC) versus SCX-IMAC-based methods for phosphopeptide
      isolation/enrichment.
AB  - Electrostatic repulsion-hydrophilic interaction chromatography (ERLIC) has been
      introduced recently for phosphopeptide enrichment. Here we compared ERLIC with
      the well-established SCX-IMAC for identifying phosphopeptides in EGF-treated A431
      cells. The ERLIC approach detected a higher number of phosphopeptides (17 311)
      than SCX-IMAC (4850), but it only detected 926 unique phosphopeptides compared to
      1315 in SCX-IMAC. Only 12% unique phosphopeptides were common to both approaches,
      suggesting that more comprehensive phosphoproteomes could be generated by
      complementing SCX-IMAC with ERLIC.

PMID- 18828628
TI  - Discovery, identification, and characterization of candidate pharmacodynamic
      markers of methionine aminopeptidase-2 inhibition.
AB  - The catalytic activity of methionine aminopeptidase-2 (MetAP2) has been
      pharmacologically linked to cell growth, angiogenesis, and tumor progression,
      making this an attractive target for cancer therapy. An assay for monitoring
      specific protein changes in response to MetAP2 inhibition, allowing
      pharmacokinetic (PK)/pharmacodynamic (PD) models to be established, could
      dramatically improve clinical decision-making. Candidate MetAP2-specific protein
      substrates were discovered from undigested cell culture-derived proteomes by
      MALDI-/SELDI-MS profiling and a biochemical method using (35)S-Met labeled
      protein lysates. Substrates were identified either as intact proteins by FT-ICR
      MS or applying in-gel protease digestions followed by LC-MS/MS. The combination
      of these approaches led to the discovery of novel MetAP2-specific substrates
      including thioredoxin-1 (Trx-1), SH3 binding glutamic acid rich-like protein
      (SH3BGRL), and eukaryotic elongation factor-2 (eEF2). These studies also
      confirmed glyceraldehye 3-phosphate dehydrogenase (GAPDH) and cyclophillin A
      (CypA) as MetAP2 substrates. Additional data in support of these proteins as
      MetAP2-specific substrates were provided by in vitro MetAP1/MetAP2 enzyme assays
      with the corresponding N-terminal derived peptides and 1D/2D Western analyses of
      cellular and tissue lysates. FT-ICR-MS characterization of all intact species of
      the 18 kDa substrate, CypA, enabled a SELDI-MS cell-based assay to be developed
      for correlating N-terminal processing and inhibition of proliferation. The MetAP2
      specific protein substrates discovered in this study have diverse properties that
      should facilitate the development of reagents for testing in preclinical and
      clinical environments.

PMID- 18828629
TI  - Physical and electrochemical properties of N-alkyl-N-methylpyrrolidinium
      bis(fluorosulfonyl)imide ionic liquids: PY13FSI and PY14FSI.
AB  - Two ionic liquids based upon N-alkyl-N-methylpyrrolidinium cations (PY(1R)(+))
      (R=3 for propyl or 4 for butyl) and the bis(fluorosulfonyl)imide (FSI(-)),
      N(SO2F)2(-), anion have been extensively characterized. The ionic conductivity
      and viscosity of these materials are found to be among the highest and lowest,
      respectively, reported for aprotic ionic liquids. Both ionic liquids crystallize
      readily on cooling and undergo several solid-solid phase transitions on heating
      prior to melting. PY13FSI and PY14FSI are found to melt at -9 and -18 degrees C,
      respectively. The thermal stability of PY13FSI and PY14FSI is notably lower than
      for the analogous salts with the bis(trifluoromethanesulfonyl)imide (TFSI(-)),
      N(SO2CF3)2(-), anion. Both ionic liquids have a relatively wide electrochemical
      stability window of approximately 5 V.

PMID- 18828630
TI  - Liquid-vapor equilibrium of the systems butylmethylimidazolium nitrate-CO2 and
      hydroxypropylmethylimidazolium nitrate-CO2 at high pressure: influence of water
      on the phase behavior.
AB  - Ionic liquids (IL) are receiving increasing attention due to their potential as
      "green" solvents, especially when used in combination with SC-CO2. In this work
      liquid-vapor equilibria of binary mixtures of CO2 with two imidazolium-based
      ionic liquids (IL) with a nitrate anion have been experimentally determined:
      butylmethylimidazolium nitrate (BMImNO3) and hydroxypropylmethylimidazolium
      nitrate (HOPMImNO3), using a Cailletet apparatus that operates according to the
      synthetic method. CO2 concentrations from 5 up to 30 mol % were investigated. It
      was found that CO2 is substantially less soluble in HOPMImNO3 than in BMImNO3.
      Since these ILs are very hygroscopic, water easily can be a major contaminant,
      causing changes in the phase behavior. In case these Ils are to be used in
      practical applications, for instance, together with CO2 as a medium in
      supercritical enzymatic reactions, it is very important to have quantitative
      information on how the water content will affect the phase behavior. This work
      presents the first systematic study on the influence of water on the solubility
      of carbon dioxide in hygroscopic ILs. It was observed that the presence of water
      reduces the absolute solubility of CO2. However, at fixed ratios of CO2/IL, the
      bubble point pressure remains almost unchanged with increasing water content. In
      order to explain the experimental results, the densities of aqueous mixtures of
      both ILs were determined experimentally and the excess molar volumes calculated.

PMID- 18828631
TI  - Effects of linker length and flexibility on multivalent targeting.
AB  - Increasing valence can enhance the ability of molecular targeting constructs to
      bind specifically to targeted cells for drug delivery. Here, we mathematically
      model the length and flexibility of a linker used to conjoin two peptide ligands
      of a divalent targeting construct and investigate the influence both on binding
      avidity and specificity. Four different models are used to approximate varying
      degrees of linker flexibility (random coil, rigid rod, jointed rods, and combined
      rod-random coil) and for each linker a binding enhancement factor (VR) is derived
      that quantifies the increased rate of each construct's second binding event over
      the first. Results indicate that the moderately flexible models can best
      reproduce experimentally measured avidities. Also, the magnitude of VR, in
      conjunction with receptor density and ligand concentration, significantly
      influences the achievable specificity. Thus, the model elucidates important
      considerations in designing multivalent targeting constructs for use in delivery
      of targeted therapy or imaging.

PMID- 18828632
TI  - A rhodamine-cyclen conjugate as a highly sensitive and selective fluorescent
      chemosensor for Hg(II).
AB  - A rhodamine-cyclen conjugate (1) behaves as a highly sensitive and selective
      fluorescent chemosensor for Hg(2+). The high emission selectivity is due to the
      formation of 1-Hg(2+) 1:2 complex leading to spirocycle opening of 1.

PMID- 18828633
TI  - Synthesis of covalently linked unsymmetrical porphyrin pentads containing three
      different porphyrin subunits.
AB  - The tetrafunctionalized AB3-type porphyrin building blocks containing two
      different types of functional groups with N4, N3O, N3S, and N2S2 porphyrin cores
      were synthesized by following various synthetic routes. The AB3-type
      tetrafunctionalized N4 porphyrin building block was synthesized by a mixed
      condensation approach, the N3S and N3O porphyrin building blocks by a mono-ol
      method, and N2S2 porphyrin building block by an unsymmetrical diol method. The
      tetrafunctionalized porphyrin building blocks were used to synthesize
      monofunctionalized porphyrin tetrads containing two different types of porphyrin
      subunits by coupling of 1 equiv of tetrafunctionalized N4, N3O, N3S, and N2S2
      porphyrin building block with 3 equiv of monofunctionalized ZnN4 porphyrin
      building block under mild copper-free Pd(0) coupling conditions. The
      monofunctionalized porphyrin tetrads were used further to synthesize
      unsymmetrical porphyrin pentads containing three different types of porphyrin
      subunits by coupling 1 equiv of monofunctionalized porphyrin tetrad with 1 equiv
      of monofunctionalized N2S2 porphyrin building blocks under the same mild Pd(0)
      coupling conditions. The NMR, absorption, and electrochemical studies on
      porphyrin tetrads and porphyrin pentads indicated that the monomeric porphyrin
      subunits in tetrads and pentads retain their individual characteristic features
      and exhibit weak interaction among the porphyrin subunits. The steady state and
      time-resolved fluorescence studies support an efficient energy transfer from
      donor porphyrin subunit to acceptor porphyrin subunit in unsymmetrical porphyrin
      tetrads and porphyrin pentads.

PMID- 18828634
TI  - Semiconducting tellurium-iron-copper carbonyl polymers.
AB  - The unprecedented ternary Te-Fe-Cu chain polymers [{Et4N}{TeFe3(CO)9Cu}]infinity
      and [{TeFe3(CO)9Cu2}(mu-4,4'-dipyridyl)1.5]infinity were prepared from the self
      assembly of [Et4N]2[TeFe3(CO)9] with [Cu(MeCN)4][BF4] in THF or in the presence
      of 4,4'-dipyridyl in THF. These two chain polymers, which can also be constructed
      from the precursor complex TeFe3(CO)9Cu2(MeCN)2, show semiconducting behaviors
      with low band gaps of 0.59 and 0.41 eV, respectively. In addition, their
      conductivity and the effect of the bridging ligand are further elucidated by
      theoretical calculations.

PMID- 18828635
TI  - Relative stability of helices determines the folding landscape of adenine
      riboswitch aptamers.
AB  - Riboswitches, whose folding is controlled by binding of metabolites to the
      aptamer domain, regulate downstream gene expression. Folding properties of the
      aptamer strongly influence the conformation of the downstream expression
      platform, which controls transcription termination or translation initiation. We
      have characterized the energy landscape of the add riboswitch aptamer
      quantitatively by unfolding and refolding the molecule with mechanical force
      using the coarse-grained self-organized polymer model and Brownian dynamics
      simulation. Multiple folding states have been found during the folding process of
      the aptamer, both with and without adenine, consistent with single molecule
      studies of purine riboswitches. Adenine binding stabilizes the folded structure
      and significantly decreases the unfolding rate of the aptamer, the folding of
      which is in competition with the formation of the downstream stem-loop structure
      in the complete riboswitch. These results provide insights into the mechanism of
      gene regulation by the RNA switches.

PMID- 18828636
TI  - Microsolvation and 13C-Li NMR coupling.
AB  - The empirical expression (1)J(CLi) = L[n(a + d)](-1) is proposed; it claims a
      reciprocal dependence of the NMR coupling constant (1)J((13)C, Li) in a C-Li
      compound on two factors: (i) the number n of lithium nuclei in bonding contact
      with the observed carbanion center and (ii) the sum (a + d) of the numbers a of
      anions and d of donor ligands coordinated at the Li nucleus that generates the
      observed (1)J(CLi) value. The expression was derived from integrations of
      separate NMR resonances of coordinated and free monodentate donor ligands (t
      BuOMe, Et2O, or THF) in toluene solutions of dimeric and monomeric 2-(alpha-aryl
      alpha-lithiomethylidene)-1,1,3,3-tetramethylindan at moderately low temperatures.
      This unusually slow ligand interchange is ascribed to steric congestion in these
      compounds, which is further characterized by measurements of nuclear Overhauser
      correlations and by solid-state structures of the dimers bearing only one donor
      per lithium atom (d = 1). Increasing microsolvation numbers d are also
      accompanied by typical changes of the NMR chemical shifts delta (positive for the
      carbanionic (13)C(alpha), negative for C(para) and p-H). The aforementioned
      empirical expression for (1)J(CLi) appears to be applicable to other cases of
      solvated monomeric, dimeric, or tetrameric C-Li compounds (alkyl, alkenyl,
      alkynyl, and aryl) and even to unsolvated (d approximately 0) trimeric,
      tetrameric, or hexameric organolithium aggregates, indicating that (1)J(CLi)
      might serve as a tool for assessing unknown microsolvation numbers. The
      importance of obtaining evidence about the (13)C NMR C-Li multiplet splitting of
      both the nonfluxional and fluxional aggregates is emphasized.

PMID- 18828637
TI  - Isolation and identification of oligomers from partial degradation of lime fruit
      cutin.
AB  - Complementary degradative treatments with low-temperature hydrofluoric acid and
      methanolic potassium hydroxide have been used to investigate the protective
      biopolymer cutin from Citrus aurantifolia (lime) fruits, augmenting prior
      enzymatic and chemical strategies to yield a more comprehensive view of its
      molecular architecture. Analysis of the resulting soluble oligomeric fragments
      with one- and two-dimensional NMR and MS methods identified a new dimer and three
      trimeric esters of primary alcohols based on 10,16-dihydroxyhexadecanoic acid and
      10-oxo-16-hydroxyhexadecanoic acid units. Whereas only 10-oxo-16
      hydroxyhexadecanoic acid units were found in the oligomers from hydrofluoric acid
      treatments, the dimer and trimer products isolated to date using diverse
      degradative methods included six of the seven possible stoichiometric ratios of
      monomer units. A novel glucoside-linked hydroxyfatty acid tetramer was also
      identified provisionally, suggesting that the cutin biopolymer can be bound
      covalently to the plant cell wall. Although the current findings suggest that the
      predominant molecular architecture of this protective polymer in lime fruits
      involves esters of primary and secondary alcohols based on long-chain
      hydroxyfatty acids, the possibility of additional cross-linking to enhance
      structural integrity is underscored by these and related findings of nonstandard
      cutin molecular architectures.

PMID- 18828638
TI  - An unlikely silk: the composite material of green lacewing cocoons.
AB  - Spiders routinely produce multiple types of silk; however, common wisdom has held
      that insect species produce one type of silk each. This work reports that the
      green lacewing ( Mallada signata, Neuroptera) produces two distinct classes of
      silk. We identified and sequenced the gene that encodes the major protein
      component of the larval lacewing cocoon silk and demonstrated that it is
      unrelated to the adult lacewing egg-stalk silk. The cocoon silk protein is 49 kDa
      in size and is alanine rich (>40%), and it contains an alpha-helical secondary
      structure. The final instar lacewing larvae spin protein fibers of approximately
      2 microm diameter to construct a loosely woven cocoon. In a second stage of
      cocoon construction, the insects lay down an inner wall of lipids that uses the
      fibers as a scaffold. We propose that the silk protein fibers provide the
      mechanical strength of the composite lacewing cocoon whereas the lipid layer
      provides a barrier to water loss during pupation.

PMID- 18828639
TI  - Kinetic analysis of intracellular concentrations of reactive nitrogen species.
AB  - Reactive nitrogen species derived from NO have been implicated in cancer and
      other diseases, but their intracellular concentrations are largely unknown. To
      estimate them under steady-state conditions representative of inflamed tissues, a
      kinetic model was developed that included the effects of cellular antioxidants,
      amino acids, proteins, and lipids. For an NO concentration of 1 microM, total
      peroxynitrite (Per, the sum of ONOO(-) and ONOOH), NO(2)(*), and N(2)O(3) were
      calculated to have concentrations in the nanomolar, picomolar, and femtomolar
      ranges, respectively. The concentrations of NO(2)(*) and N(2)O(3) were predicted
      to decrease markedly with increases in glutathione (GSH) levels, due to the
      scavenging of each by GSH. Although lipids accelerate the oxidation of NO by O(2)
      (because of the high solubility of each in hydrophobic media), lipid-phase
      reactions were calculated to have little effect on NO(2)(*) or N(2)O(3)
      concentrations. The major sources of intracellular NO(2)(*) were found to be the
      reaction of Per with metals and with CO(2), whereas the major sinks were its
      reactions with GSH and ascorbate (AH(-)). The radical-scavenging ability of GSH
      and AH(-) caused 3-nitrotyrosine to be the only tyrosine derivative predicted to
      be formed at a significant rate. The major GSH reaction product was S
      nitrosoglutathione. Analytical (algebraic) expressions are provided for the
      concentrations of the key reactive intermediates, allowing the calculations to be
      extended readily.

PMID- 18828640
TI  - Pharmacologic inhibition of platelet function: correlation between in vitro tests
      of platelet function and clinical outcomes.
AB  - Atherothrombosis continues to be a leading cause of death and disability despite
      advances in pharmacologic and procedural therapies. Antiplatelet agents have been
      extensively studied and validated to improve outcomes in multiple settings of
      cardiovascular disease. The emergence of the phenomenon of resistance to
      antiplatelet therapy resulted in the availability of platelet function tests to
      assess the effectiveness of these agents. Subsequent evaluations have shown
      considerable inter-individual variability in platelet inhibition in patients
      receiving antiplatelet agents. Several small studies showed that patients who
      were deemed 'resistant' to antiplatelet therapy by platelet function testing had
      adverse clinical outcomes. It is essential that ongoing investigations help
      delineate a standard definition of 'resistance' to antiplatelet therapy, which
      test of platelet function should be the gold standard, and what therapy, once
      identified, can help overcome resistance to the currently available antiplatelet
      agents. Data are needed to determine if outcomes can be improved by changes to
      existing antiplatelet therapy based on the results of platelet function tests.
      Alternatively, newer antiplatelet agents may prove effective in overcoming
      resistance; however, these agents also await validation in large-scale clinical
      trials.

PMID- 18828641
TI  - Do statins have a role in the management of diastolic dysfunction?
AB  - Diastolic dysfunction of the left ventricle is an increasingly recognized
      clinical entity that may in some cases cause overt congestive heart failure.
      Currently, treatment of these patients is based on limited studies in patients
      with symptomatic heart failure. HMG-CoA reductase inhibitor (statin) drugs, which
      are primarily used for the treatment of hyperlipidemia, have been shown to have
      additional pharmacologic properties that may be beneficial in other disease
      states such as heart failure. Here, we wish to review the current knowledge of
      the mechanism of action of statins and the probable implications for asymptomatic
      patients with diastolic dysfunction. We discuss the causes and settings of
      diastolic dysfunction, the potential role of statin therapy in the treatment of
      diastolic dysfunction, and potential mechanisms by which statins may show
      benefit. The use of statins in the setting of diastolic dysfunction, both for
      treatment of established heart failure as well as to prevent progression of
      subclinical disease to overt symptomatic expression, is an area of substantial
      research interest with direct clinical application.

PMID- 18828642
TI  - Fully biodegradable coronary stents : progress to date.
AB  - The limitations of currently available metallic drug-eluting stents have renewed
      interest in biodegradable stents (BDS). Apart from removing the (offending)
      foreign material that may potentiate a thrombotic event, BDS have the advantage
      of avoiding 'full metal jackets,' and thus can preclude subsequent coronary
      surgery. In addition, they do not interfere with the diagnostic evaluation of non
      invasive imaging such as cardiac magnetic resonance and CT. There are now several
      BDS in development or in clinical trials that incorporate a variety of
      biodegradable polymer technologies. Two broad categories of materials are
      generally used: those made from organic biopolymers and those made from
      corrodible metals. However, to date, none of the materials/stents tested have
      been able to establish a perfect balance between biocompatibility, the kinetics
      of degradation needed to maintain mechanical strength to limit recoil, and
      inflammation. However, studies, such as the ABSORB trial with the everolimus
      eluting poly-L-lactide stent, which demonstrated comparable restenotic rates with
      bare metallic stents and a low incidence of major adverse cardiac events (MACE)
      at 12 months of 3.3%, with only one patient having a non-Q-wave myocardial
      infarction and no target lesion revascularization, suggest that there has been
      significant progress with respect to the earlier prototypes. The acute recoil
      observed could potentially be addressed with the polytyrosine REVA stent
      currently being evaluated in the RESORB trial, which incorporates a novel locking
      mechanism within its design. Alternative BDS designs include the combination of
      an antiproliferative drug with endothelial progenitor cell capturing antibodies
      to facilitate epithelialization and/or dual eluting having, in addition to the
      antiproliferative drug, polymeric salicyclic acid to limit inflammation. Compared
      with biodegradable polymers, there are fewer metals used in the manufacture of
      BDS. The only metal BDS in trials is the Biotronik absorbable magnesium stent,
      which showed a MACE of 26.7% at 12 months without deaths, stent thrombosis, or
      acute myocardial infarction in the PROGRESS-AMS trial. Unlike magnesium stents,
      there has been little progress with iron stents, which remain in the pre-clinical
      phase, and this may be partly due to the longer degradation times needed and
      potential issues related with iron clearance.

PMID- 18828643
TI  - Therapeutic potential of adult progenitor cells in the management of chronic
      myocardial ischemia.
AB  - Refractory angina as a result of chronic myocardial ischemia is a common and
      disabling condition. Adult progenitor cells have emerged as a potential
      revolutionary treatment for cardiovascular disease. Locally administered adult
      progenitor cells with particular vasculogenic potential may offer treatment hope
      for those with chronic ischemia; however, the optimal cell type, dose, delivery
      mode, and target patient population has not been defined. Preclinical cell
      therapy studies have shown safety and efficacy sufficient to warrant human
      trials. Early, small-scale human trials exploring various cell types and delivery
      modes have shown that most approaches are safe, with modest early efficacy. This
      overview discusses the rationale and early results for ongoing larger
      cardiovascular disease trials, with a special emphasis on refractory angina and
      chronic myocardial ischemia.

PMID- 18828644
TI  - Thrombocytopenia associated with antithrombotic therapy in patients with
      cardiovascular diseases: diagnosis and treatment.
AB  - Agents with antiplatelet and anticoagulant activity have been proved to be
      effective in reducing the incidence of complications following acute coronary
      syndrome, percutaneous coronary intervention, and cardiopulmonary bypass.
      However, these agents, including heparin, glycoprotein IIb/IIIa receptor
      inhibitors, and thienopyridines, are associated with increased risk of bleeding
      and thrombocytopenia and have been administered together with increasing
      frequency in a variety of cardiovascular settings. Therefore, clinicians must be
      familiar with the safety and rational use of these potent antithrombotic agents.
      Clinical features of thrombocytopenia range from bleeding to thrombosis, even
      death, and therapy is very different depending on the underlying cause.
      Additionally, patients may sometimes need urgent intervention or surgery. Thus,
      it is essential to quickly discriminate the etiology and start appropriate
      therapy. This review highlights the pathogenesis, clinical and laboratory
      manifestation, differential diagnosis, and treatment of antithrombotic drug
      induced thrombocytopenia in cardiovascular diseases.

PMID- 18828645
TI  - Intravenous conivaptan.
AB  - *Conivaptan is an arginine vasopressin V1A and V2 receptor antagonist. The
      intravenous formulation is approved in the US for use in the treatment of
      euvolemic and hypervolemic hyponatremia. Conivaptan produces a dose-dependent
      electrolyte-sparing aquaresis (solute-free water excretion), increasing serum
      sodium levels. *In a randomized, double-blind, parallel-group, placebo
      controlled, multicenter trial in adults with euvolemic or hypervolemic
      hyponatremia, the area under the serum sodium concentration-time curve over a 4
      day treatment duration (primary endpoint) was significantly greater in
      intravenous conivaptan 40 mg/day recipients than in placebo recipients. *The
      total time during treatment that patients had serum sodium levels > or = 4 mEq/L
      above baseline was significantly longer in intravenous conivaptan than placebo
      recipients. In conivaptan recipients, an increase in serum sodium levels of > or
      = 4 mEq/L above baseline was achieved approximately 1 day after the first dose of
      the drug. *In addition, the mean change from baseline in free water clearance and
      effective water clearance over the first day of treatment was significantly
      greater with intravenous conivaptan than with placebo. *Given the nature of the
      treatment, the tolerability profile for intravenous conivaptan was generally
      acceptable in patients with hyponatremia. The most common adverse events were
      injection related (e.g. injection-site phlebitis), hypotension, and pyrexia.

PMID- 18828647
TI  - Learning to EXHALE: don't catch the flu this season!
AB  - Decrease your chances of getting the flu by first, getting your flu shot, and
      second, by adopting this three-step technique to help prevent the spread of
      influenza as well as other viral respiratory illnesses. Like cough etiquette (ie,
      covering your nose and mouth when coughing or sneezing) and hand washing, this
      easily implemented, noninvasive technique should be an additional component of
      respiratory hygiene. The three steps are exhale, look away, and walk away.

PMID- 18828648
TI  - Tight blood glucose control.

PMID- 18828649
TI  - Tight blood glucose control.

PMID- 18828650
TI  - Herpes zoster virus vaccine.
AB  - Varicella zoster virus (VZV) is the etiologic agent of varicella and herpes
      zoster (HZ) in humans. Herpes zoster is the result of reactivation of VZV within
      certain sensory ganglia. The burden of illness from HZ and post-herpetic
      neuralgia (PHN) is high. Herpes-zoster vaccine contains live attenuated varicella
      zoster virus in an amount approximately 14 times greater than that found in the
      varicella virus vaccine. Herpes zoster vaccine is approved for the prevention of
      shingles in appropriate persons aged 60 and older. The vaccine is administered in
      a single subcutaneous dose. Reported side effects are mild and generally limited
      to localized injection site findings. Herpes-zoster vaccine reportedly decreases
      the occurrence of herpes zoster by approximately 50 percent and prevents the
      development of PHN by two thirds. The vaccine appears to be minimally effective
      in those individuals over the age of 80 and is not recommended in this age group.

PMID- 18828651
TI  - Risk prediction after TIA: the ABCD system and other methods.
AB  - Transient ischemic attack (TIA) is common in the elderly and total numbers are
      likely to increase with the aging of the population. The risk of stroke early
      after TIA has recently been shown to be approximately 5 percent at 7 days and 10
      to 15 percent at 3 months, while overall cardiovascular risk is increased in the
      longer term. The ABCD system (Age, Blood pressure, Clinical features, Duration of
      symptoms) is a clinical score that can be rapidly worked out at the time of
      presentation and reliably predicts early risk of stroke. It can be used in
      patient triage to secondary care, informing public education and in the effective
      targeting of secondary prevention. The vascular territory and etiology of the TIA
      and results of cerebral imaging can also be used to predict early risk of stroke
      but the degree of the interaction between all these factors is uncertain.

PMID- 18828652
TI  - Hypertension 2008, refining our treatment.
AB  - Clinical studies continue to modify our approach to the older hypertensive
      patient. The pathophysiology of hypertension is now better understood from data
      derived from ambulatory blood pressure monitoring, the assessment of central
      arterial pressure and of vascular stiffness. This is altering both the ways we
      assess, monitor, and treat our older hypertensive patients as well as our choice
      of pharmacological agents. New data have confirmed the importance of treating the
      very elderly patient's blood pressure and of modifying the increasing incidence
      of atrial fibrillation. Resistant hypertension is frequently the result of
      excessive aldosterone production, a situation easily treated. Several
      investigators have raised the question of the prehypertensive state and of
      possible therapy.

PMID- 18828653
TI  - Treatment of hypertension in the elderly.
AB  - Numerous double-blind, randomized, placebo-controlled studies have shown that
      antihypertensive drug therapy reduces cardiovascular events in elderly persons.
      In the Hypertension in the Very Elderly Trial, patients aged 80 years and older
      treated with antihypertensive drug therapy had, at 1.8-year follow-up, a 30
      percent reduction in fatal or nonfatal stroke, a 39 percent reduction in fatal
      stroke, a 21 percent reduction in all-cause mortality, a 23 percent reduction in
      death from cardiovascular causes, and a 64 percent reduction in heart failure.
      The goal of treatment of hypertension in elderly persons is to lower the blood
      pressure to less than 140/90 mmHg and to less than 130/80 mmHg in older persons
      with diabetes or chronic renal insufficiency. All antihypertensive drugs may
      predispose the elderly person to develop symptomatic orthostatic hypotension and
      postprandial hypotension and syncope or falls. Adverse effects depend upon the
      antihypertensive drugs used, the doses of these drugs, the comorbidities in the
      elderly patients taking these drugs, and drug-drug interactions.

PMID- 18828654
TI  - Intermittently painful lesion in mouth.

PMID- 18828655
TI  - Changes in the expression of soluble and integral-membrane trehalases in the
      midgut during metamorphosis in Bombyx mori.
AB  - To elucidate the relationship between soluble trehalase (Treh1) and integral
      membrane trehalase (Treh2) in the Bombyx mori midgut, expression profiles for
      both proteins and mRNAs were examined during metamorphosis by using Western
      blotting and quantitative real-time PCR analyses. Two bands of Treh2 (about 74
      kDa) were detected in the midgut of 0-day-old 5th (last) instar larvae. Levels of
      Treh2 decreased as the developing larvae approached spinning (8 days old). In
      contrast, towards the onset of the spinning stage, Treh1 (68 kDa) was clearly
      observed, and levels increased until the middle of the pupal stage. Treh2 mRNA
      expression relative to Bmrp49 mRNA expression was almost constant, although
      fluctuations were detected. Treh1 mRNA expression relative to Bmrp49 mRNA
      increased sharply just after spinning. To further examine the expression
      mechanism of the Treh1 gene in midgut, actively feeding larvae (4 days old) were
      starved or ligated between the 4th and 5th segments. Injection of a molting
      hormone into the larval-isolated abdomen led to activation of Treh1,
      demonstrating that molting hormone acts on the midgut and activates this gene.

PMID- 18828656
TI  - Compound eye development during caste differentiation in the termite
      Reticulitermes speratus (Isoptera: Rhinotermitidae).
AB  - We morphologically examined postembryonic compound eye development in
      Reticulitermes speratus (Kolbe) to understand developmental regulation during
      caste differentiation. The eye primordia were shown to exist from the larval
      stage. The number of ommatidia and compound eye size greatly increased over the
      course of imaginal development. Nymphoids (second-form reproductives) possessed a
      developed compound eye structure on the surface of the cuticle and thick optic
      nerves, but individual ommatidia were not clearly discriminated. However, in the
      line of apterous workers and soldiers, although the outer rim of the eye was
      observed from second-stage workers, there were few morphological differences
      among instars, including ergatoids (third-form reproductives). Both nymphoids and
      ergatoids are slightly physogastric and have highly developed reproductive
      organs. These results suggest that eye development in the apterous line could be
      strongly arrested and that there is a weak developmental correlation between the
      eyes and reproductive organs in R. speratus.

PMID- 18828657
TI  - TRIQK, a novel family of small proteins localized to the endoplasmic reticulum
      membrane, is conserved across vertebrates.
AB  - Here we report a novel small protein that is highly conserved across vertebrates.
      The protein, which we have named TRIQK, has no homology to any previously
      reported proteins or functional domains, but all vertebrate homologs of this
      protein share a characteristic triple repeat of the sequence QXXK/R, as well as a
      hydrophobic C-terminal region. The Xenopus triqk gene (xTriqk) was isolated in an
      expression screen on the basis of its ability to cause dramatic changes in cell
      size and nuclear size and morphology in developing embryos. The Xenopus and mouse
      triqk genes are broadly expressed throughout embryogenesis, and mtriqk is also
      generally expressed in mouse adult tissues. TRIQK proteins are localized to the
      endoplasmic reticulum membrane. Depletion of endogenous xTRIQK protein in Xenopus
      embryos causes no detectable morphological or functional changes in tadpoles.

PMID- 18828658
TI  - Genetic identification of mammalian carnivore species in the Kushiro Wetland,
      eastern Hokkaido, Japan, by analysis of fecal DNA.
AB  - To identify mammalian carnivore species distributed in the Kushiro Wetland,
      eastern Hokkaido, Japan, we developed molecular-genetic methods for
      identification of the species from fecal samples collected from the field.
      Species-specific primers and PCR programs were established for five native and
      six alien species of carnivores: Martes zibellina, Mustela nivalis, Mustela
      erminea, Vulpes vulpes, and Nyctereutes procyonoides as native species, and
      Neovison vison, Martes melampus, Mustela itatsi, Canis familiaris, Felis catus,
      and Procyon lotor as alien species in Hokkaido. Touchdown PCR, in which the
      annealing temperature is decreased 1 degrees C every cycle, was more effective
      for some species from which fecal DNA was not amplified species-specifically with
      standard PCR programs. Of 405 fecal samples collected from the Kushiro Wetland,
      the species of origin of 246 samples were successfully identified: 88 samples for
      N. vison, 140 for M. zibellina, 13 for V. vulpes, four for C. familiaris and one
      for F. catus. The results show the particular applicability of this method to
      monitoring M. zibellina and N. vison. In addition, methods to PCR-amplify DNA
      from two crayfish species (Pacifastacus leniusculus and Cambaroides japonicus)
      were developed to determine whether the carnivore fecal samples contained
      detectable DNA from the prey crayfishes. DNA from P. leniusculus was amplified
      from feces of N. vison identified in the present study, but no DNA from C.
      japonicus was detected. This indicates that N. vison preys on the alien species
      P. leniusculus.

PMID- 18828659
TI  - Synthesis and phosphorylation of ecdysteroids during ovarian development in the
      silkworm, Bombyx mori.
AB  - In the silkworm, Bombyx mori, it has been demonstrated that most free
      ecdysteroids in the ovary are converted to physiologically inactive ecdysteroid
      22-phosphates, which are then transformed back to free ecdysteroids during early
      embryonic development. Two specific enzymes involved in the reciprocal conversion
      of ecdysteroids, namely, ecdysteroid 22-kinase (EcKinase) and ecdysteroid
      phosphate phosphatase, have been isolated and characterized. In this study, we
      first attempted a phylogenetic analysis of EcKinase. The resulting phylogenetic
      tree showed that many proteins homologous to B. mori EcKinase are found not only
      in ecdysozoa, including insects and nematodes, but also in teleosts, fungi, and
      bacteria. We then investigated the sites where free ecdysteroids are synthesized
      and phosphorylated in the ovary. We found that (1) the mRNAs of two P450 enzymes
      involved in ecdysteroidogenesis, CYP306a1 (25-hydroxylase) and CYP314a1 (20
      hydroxylase), are expressed mainly in follicle cells, (2) EcKinase mRNA localizes
      in the oocyte and nurse cells, and (3) EcKinase immunoreactivity localizes mainly
      in the external region of the oocyte, not in nurse cells or follicle cells. From
      these results, we suggest that ecdysteroids in the B. mori ovary are synthesized
      in follicle cells and transferred into the oocyte, where they are phosphorylated
      by EcKinase, whose mRNA originates from nurse cells and the oocyte itself.

PMID- 18828660
TI  - Molecular cloning of stanniocalcin 1 and its extracorpuscular regulation by
      salinity and Ca2+ in the Japanese flounder.
AB  - Stanniocalcin 1 (Stc1) was originally identified as an anti-hypercalcemic hormone
      produced by the corpuscles of Stannius (CS) associated with the kidney in
      teleosts. While the stc1 gene is expressed in various tissues in fishes, its role
      and regulation in extra-CS tissues are unexplored. In the present study, we
      characterized a cDNA of stc1 in a euryhaline fish, the Japanese flounder
      (Paralichyhus olivaceus), and examined its expression in peripheral tissues in
      response to different salinities and Ca2+ ion concentrations. The Japanese
      flounder stc1 cDNA (1331 bp) encodes a preprohormone of 251 amino acids (aa),
      with a signal peptide of 17 aa and a pro-sequence peptide of 15 aa followed by
      the mature protein of 219 aa. The deduced aa sequence of Japanese flounder stc1
      showed highest sequence identity (94.0%) with the European flounder Stc1 among
      fish and mammalian species, but lower identity to zebrafish, pufferfish, and
      human STC2 (23.1-25.4%). Lowered environmental salinity resulted in a decrease in
      stc1 mRNA expression in vivo in the gills, kidney, intestine, and CS glands of
      the Japanese flounder. Furthermore, we found that extracellular Ca2+ increased
      steady-state stc1 mRNA levels in gill and kidney cells as well as in the CS
      cells. Our findings suggest that Stc1 synthesis in the ionregulatory tissues is
      responsive to environmental salinity and Ca2+ level.

PMID- 18828661
TI  - Prolactin inhibits osteoclastic activity in the goldfish scale: a novel direct
      action of prolactin in teleosts.
AB  - In teleosts, prolactin is involved in calcium regulation, but its role in
      scale/bone metabolism is unclear. Using the in-vitro system with goldfish scales
      developed recently, we explored the effects of teleost prolactin, growth hormone,
      and somatolactin on osteoclasts and osteoblasts. Addition of prolactin at
      concentrations of 0.01-100 ng/ml reduced osteoclastic activity, partly via
      osteoclast apoptosis, after 6-18 h incubation. Conversely, growth hormone and
      somatolactin at a concentration of 100 ng/ml increased osteoclastic activity
      after 18 h incubation, indicating the specificity of the inhibitory effect of
      prolactin on osteoclastic activity. On the other hand, these three hormones
      promoted osteoblastic activity at concentrations of 10-100 ng/ml. The results
      from this study are the first demonstration of direct effects of prolactin on
      scale/bone metabolism and osteoclastic activity in a teleost.

PMID- 18828662
TI  - Analysis of hunger-driven gene expression in the Drosophila melanogaster larval
      central nervous system.
AB  - A transposon-inserted mutant of Drosophila melanogaster was recently identified,
      and the larvae show no food preference (Ryuda and Hayakawa, 2005). To reveal the
      genetic mechanism underlying the preference change in this mutant, a large-scale
      oligo-DNA microarray screening was carried out to identify genes whose expression
      is different in control and mutant strains. We focused especially on hunger
      driven changes in gene expression in the larval central nervous system (CNS) of
      both strains, because the state of food depletion should promote a feeding
      response due to changed expression of certain genes in the CNS. We identified 22
      genes whose expression changed after starvation in either or both of the two
      strains. Quantitative RT-PCR analyses confirmed the expression changes in four
      genes, CG6271, CG6277, CG7953, and new glue 3 (ng3, encoding a putative
      structural molecule). CG6271 and CG6277 encode triacylglycerol lipase, and CG7953
      produces a protein homologous to a juvenile hormone (JH) binding protein. The
      expression of these two groups of genes was enhanced in control strain larvae
      with a normal food preference but not in GS1189 strain larvae. Given that these
      genes contribute to mediating hunger-driven changes in food preference and intake
      in D. melanogaster larvae, the dysfunction of these key genes could cause the
      defect in food preference observed in GS1189-strain larvae.

PMID- 18828663
TI  - Degeneration of the midgut epithelium in Allacma fusca L. (Insecta, Collembola,
      Symphypleona): apoptosis and necrosis.
AB  - Apoptotic and necrotic changes in the midgut epithelium cells of Allacma fusca
      (Collembola, Symphypleona) are described at the ultrastructural level. The
      morphological sign indicating the beginning of the apoptotic process in these
      cells is their shrinkage and the transformation of their mitochondria. The
      nucleus assumes a lobular shape and finally undergoes fragmentation. The
      intercellular junctions between an apoptotic cell and adjacent epithelial cells
      gradually disappear. Apoptotic cells are discharged into the midgut lumen just
      beneath the peritrophic membrane, where they are initially distributed singly but
      ultimately form a single layer. No phagocytosis was observed, so no apoptotic
      bodies are formed. Only young midgut epithelium shows apoptosis; as cells age,
      necrosis accompanies apoptosis, and necrosis finally completely replaces
      apoptosis.

PMID- 18828664
TI  - Detection and changes in levels of testosterone during spermatogenesis in the
      freshwater planarian Bdellocephala brunnea.
AB  - It was reported recently that vertebrate-type steroids exist and control
      reproduction in several groups of invertebrates, including molluscs. Sexually
      reproductive freshwater planarians of the species Bdellocephala brunnea have a
      limited breeding season in their natural habitat. This phenomenon suggests that
      some endogenous reproductive hormones might play a role in vivo. However, to
      date, sex steroids such as androgen, estrogen, and progesterone have not been
      found in planarians. The goal of the present study was to determine whether
      androgen is present in sexual planarians such as B. brunnea. The presence of
      testosterone was detected by high-pressure liquid chromatography and, in sexually
      reproductive individuals in which no seminal vesicles were visible, the level of
      testosterone was about twice than that in individuals with visible seminal
      vesicles. An enzyme-linked immunosorbent assay revealed that the levels of
      testosterone during terminal spermatogenesis were three times higher than during
      the spermatocyte-building phase. Our results indicate that sexually reproductive
      freshwater planarians such as B. brunnea might have vertebrate-type steroids and
      show variation in testosterone levels during spermatogenesis.

PMID- 18828665
TI  - Synchronous female spawning and male mating behavior in a land-locked population
      of Japanese charr, Salvelinus leucomaenis japonicus.
AB  - In resource-based promiscuous mating systems, synchronous spawning of females
      affects competition among males and variation in the reproductive success of
      males. We documented the mating behavior of Japanese charr (Salvelinus
      leucomaenis japonicus) through an annual breeding season to examine the
      relationship between female spawning synchrony and male mating behavior. Females
      spawned highly synchronously in the population studied, i.e., approximately half
      the spawning was finished within the first three days of the entire spawning
      season (11 days). The daily operational sex ratio (OSR) was nearly 1:1 through
      the spawning period. The number of males around a spawning female was very small
      (1.21+/-0.49 males per female) over the spawning ground and period, suggesting
      that a competitive male could effectively chase subordinate males away from a
      spawning female. A few males attempted to sneak near the oviposition site of
      females (16%; 9 of 57 breeding groups), while some males adopted sneaking tactics
      in the initial phase of females' spawning (24%). We did not observe any males to
      succeed in sneak fertilizations. We conclude that in this Japanese charr
      population, the synchronous spawning of females was related to the unbiased daily
      OSR, male aggregation around females, and consequently whether and how
      efficiently males engaged in sneak mating behavior.

PMID- 18828666
TI  - Possible involvement of phosphatidylinositol 3-kinase, but not protein kinase B
      or glycogen synthase kinase 3beta, in progesterone-induced oocyte maturation in
      the Japanese brown frog, Rana japonica.
AB  - It is known that amphibian oocytes undergo maturation through the formation and
      activation of maturation-promoting factor (MPF) in response to stimulation by the
      maturation-inducing hormone progesterone; however, the signal transduction
      pathway that links the hormonal stimulation on the oocyte surface to the
      activation of MPF in the oocyte cytoplasm remains a mystery. The aim of this
      study was to investigate whether the signal transduction mediated by
      phosphatidylinositol 3-kinase (PI3K), protein kinase B (PKB), and glycogen
      synthase kinase 3beta (GSK3beta) is involved in progesterone-induced oocyte
      maturation in the Japanese brown frog, Rana japonica. Inhibitors of PI3K,
      wortmannin and LY294002, inhibited progesterone-stimulated germinal vesicle
      breakdown (GVBD) only when the oocytes were treated at the initial phase of
      maturation, suggesting that PI3K is involved in the progesterone-induced
      maturation of Rana oocytes. However, we also obtained results suggesting that PKB
      and GSK3beta are not involved in Rana oocyte maturation. A constitutively active
      PKB expressed in the oocytes failed to induce GVBD in the absence of progesterone
      despite its high level of kinase activity. A Myc-tagged PKB expressed in the
      oocytes (used to monitor endogenous PKB activity) was not activated in the
      process of progesterone-induced oocyte maturation. Overexpression of GSK3beta,
      which is reported to retard the progress of Xenopus oocyte maturation, had no
      effect on Rana oocyte maturation. On the basis of these results, we propose that
      PI3K is involved in the initiation of Rana oocyte maturation, but that neither
      PKB nor GSK3beta is a component of the PI3K signal transduction pathway.

PMID- 18828667
TI  - Birth size and breast cancer risk: re-analysis of individual participant data
      from 32 studies.
AB  - BACKGROUND: Birth size, perhaps a proxy for prenatal environment, might be a
      correlate of subsequent breast cancer risk, but findings from epidemiological
      studies have been inconsistent. We re-analysed individual participant data from
      published and unpublished studies to obtain more precise estimates of the
      magnitude and shape of the birth size-breast cancer association. METHODS AND
      FINDINGS: Studies were identified through computer-assisted and manual searches,
      and personal communication with investigators. Individual participant data from
      32 studies, comprising 22,058 breast cancer cases, were obtained. Random effect
      models were used, if appropriate, to combine study-specific estimates of effect.
      Birth weight was positively associated with breast cancer risk in studies based
      on birth records (pooled relative risk [RR] per one standard deviation [SD] [=
      0.5 kg] increment in birth weight: 1.06; 95% confidence interval [CI] 1.02-1.09)
      and parental recall when the participants were children (1.02; 95% CI 0.99-1.05),
      but not in those based on adult self-reports, or maternal recall during the
      woman's adulthood (0.98; 95% CI 0.95-1.01) (p for heterogeneity between data
      sources = 0.003). Relative to women who weighed 3.000-3.499 kg, the risk was 0.96
      (CI 0.80-1.16) in those who weighed < 2.500 kg, and 1.12 (95% CI 1.00-1.25) in
      those who weighed > or = 4.000 kg (p for linear trend = 0.001) in birth record
      data. Birth length and head circumference from birth records were also positively
      associated with breast cancer risk (pooled RR per one SD increment: 1.06 [95% CI
      1.03-1.10] and 1.09 [95% CI 1.03-1.15], respectively). Simultaneous adjustment
      for these three birth size variables showed that length was the strongest
      independent predictor of risk. The birth size effects did not appear to be
      confounded or mediated by established breast cancer risk factors and were not
      modified by age or menopausal status. The cumulative incidence of breast cancer
      per 100 women by age 80 y in the study populations was estimated to be 10.0,
      10.0, 10.4, and 11.5 in those who were, respectively, in the bottom, second,
      third, and top fourths of the birth length distribution. CONCLUSIONS: This pooled
      analysis of individual participant data is consistent with birth size, and in
      particular birth length, being an independent correlate of breast cancer risk in
      adulthood.

PMID- 18828668
TI  - Birth size and the pathogenesis of breast cancer.

PMID- 18828669
TI  - Animal models of inflammatory bowel disease at the dawn of the new genetics era.

PMID- 18828670
TI  - Making sense of non-financial competing interests.

PMID- 18828671
TI  - Interconvertible lac repressor-DNA loops revealed by single-molecule experiments.
AB  - At many promoters, transcription is regulated by simultaneous binding of a
      protein to multiple sites on DNA, but the structures and dynamics of such
      transcription factor-mediated DNA loops are poorly understood. We directly
      examined in vitro loop formation mediated by Escherichia coli lactose repressor
      using single-molecule structural and kinetics methods. Small ( approximately 150
      bp) loops form quickly and stably, even with out-of-phase operator spacings.
      Unexpectedly, repeated spontaneous transitions between two distinct loop
      structures were observed in individual protein-DNA complexes. The results imply a
      dynamic equilibrium between a novel loop structure with the repressor in its
      crystallographic "V" conformation and a second structure with a more extended
      linear repressor conformation that substantially lessens the DNA bending strain.
      The ability to switch between different loop structures may help to explain how
      robust transcription regulation is maintained even though the mechanical work
      required to form a loop may change substantially with metabolic conditions.

PMID- 18828672
TI  - Caenorhabditis elegans HCF-1 functions in longevity maintenance as a DAF-16
      regulator.
AB  - The transcription factor DAF-16/forkhead box O (FOXO) is a critical longevity
      determinant in diverse organisms, however the molecular basis of how its
      transcriptional activity is regulated remains largely unknown. We report that the
      Caenorhabditis elegans homolog of host cell factor 1 (HCF-1) represents a new
      longevity modulator and functions as a negative regulator of DAF-16. In C.
      elegans, hcf-1 inactivation caused a daf-16-dependent lifespan extension of up to
      40% and heightened resistance to specific stress stimuli. HCF-1 showed ubiquitous
      nuclear localization and physically associated with DAF-16. Furthermore, loss of
      hcf-1 resulted in elevated DAF-16 recruitment to the promoters of its target
      genes and altered expression of a subset of DAF-16-regulated genes. We propose
      that HCF-1 modulates C. elegans longevity and stress response by forming a
      complex with DAF-16 and limiting a fraction of DAF-16 from accessing its target
      gene promoters, and thereby regulates DAF-16-mediated transcription of selective
      target genes. As HCF-1 is highly conserved, our findings have important
      implications for aging and FOXO regulation in mammals.

PMID- 18828673
TI  - L-DOPA is an endogenous ligand for OA1.
AB  - Albinism is a genetic defect characterized by a loss of pigmentation. The
      neurosensory retina, which is not pigmented, exhibits pathologic changes
      secondary to the loss of pigmentation in the retina pigment epithelium (RPE). How
      the loss of pigmentation in the RPE causes developmental defects in the adjacent
      neurosensory retina has not been determined, but offers a unique opportunity to
      investigate the interactions between these two important tissues. One of the
      genes that causes albinism encodes for an orphan GPCR (OA1) expressed only in
      pigmented cells, including the RPE. We investigated the function and signaling of
      OA1 in RPE and transfected cell lines. Our results indicate that OA1 is a
      selective L-DOPA receptor, with no measurable second messenger activity from two
      closely related compounds, tyrosine and dopamine. Radiolabeled ligand binding
      confirmed that OA1 exhibited a single, saturable binding site for L-DOPA.
      Dopamine competed with L-DOPA for the single OA1 binding site, suggesting it
      could function as an OA1 antagonist. OA1 response to L-DOPA was defined by
      several common measures of G-protein coupled receptor (GPCR) activation,
      including influx of intracellular calcium and recruitment of beta-arrestin.
      Further, inhibition of tyrosinase, the enzyme that makes L-DOPA, resulted in
      decreased PEDF secretion by RPE. Further, stimulation of OA1 in RPE with L-DOPA
      resulted in increased PEDF secretion. Taken together, our results illustrate an
      autocrine loop between OA1 and tyrosinase linked through L-DOPA, and this loop
      includes the secretion of at least one very potent retinal neurotrophic factor.
      OA1 is a selective L-DOPA receptor whose downstream effects govern spatial
      patterning of the developing retina. Our results suggest that the retinal
      consequences of albinism caused by changes in melanin synthetic machinery may be
      treated by L-DOPA supplementation.

PMID- 18828674
TI  - Regulatory hotspots in the malaria parasite genome dictate transcriptional
      variation.
AB  - The determinants of transcriptional regulation in malaria parasites remain
      elusive. The presence of a well-characterized gene expression cascade shared by
      different Plasmodium falciparum strains could imply that transcriptional
      regulation and its natural variation do not contribute significantly to the
      evolution of parasite drug resistance. To clarify the role of transcriptional
      variation as a source of stain-specific diversity in the most deadly malaria
      species and to find genetic loci that dictate variations in gene expression, we
      examined genome-wide expression level polymorphisms (ELPs) in a genetic cross
      between phenotypically distinct parasite clones. Significant variation in gene
      expression is observed through direct co-hybridizations of RNA from different P.
      falciparum clones. Nearly 18% of genes were regulated by a significant expression
      quantitative trait locus. The genetic determinants of most of these ELPs resided
      in hotspots that are physically distant from their targets. The most prominent
      regulatory locus, influencing 269 transcripts, coincided with a Chromosome 5
      amplification event carrying the drug resistance gene, pfmdr1, and 13 other
      genes. Drug selection pressure in the Dd2 parental clone lineage led not only to
      a copy number change in the pfmdr1 gene but also to an increased copy number of
      putative neighboring regulatory factors that, in turn, broadly influence the
      transcriptional network. Previously unrecognized transcriptional variation,
      controlled by polymorphic regulatory genes and possibly master regulators within
      large copy number variants, contributes to sweeping phenotypic evolution in drug
      resistant malaria parasites.

PMID- 18828675
TI  - A specificity map for the PDZ domain family.
AB  - PDZ domains are protein-protein interaction modules that recognize specific C
      terminal sequences to assemble protein complexes in multicellular organisms. By
      scanning billions of random peptides, we accurately map binding specificity for
      approximately half of the over 330 PDZ domains in the human and Caenorhabditis
      elegans proteomes. The domains recognize features of the last seven ligand
      positions, and we find 16 distinct specificity classes conserved from worm to
      human, significantly extending the canonical two-class system based on position 
      2. Thus, most PDZ domains are not promiscuous, but rather are fine-tuned for
      specific interactions. Specificity profiling of 91 point mutants of a model PDZ
      domain reveals that the binding site is highly robust, as all mutants were able
      to recognize C-terminal peptides. However, many mutations altered specificity for
      ligand positions both close and far from the mutated position, suggesting that
      binding specificity can evolve rapidly under mutational pressure. Our specificity
      map enables the prediction and prioritization of natural protein interactions,
      which can be used to guide PDZ domain cell biology experiments. Using this
      approach, we predicted and validated several viral ligands for the PDZ domains of
      the SCRIB polarity protein. These findings indicate that many viruses produce PDZ
      ligands that disrupt host protein complexes for their own benefit, and that
      highly pathogenic strains target PDZ domains involved in cell polarity and
      growth.

PMID- 18828676
TI  - Tolerance to self: which cells kill?

PMID- 18828678
TI  - Evaluation of differences between breeds for substance P, vasoactive intestinal
      polypeptide, and neurofilament 200 in the abomasal wall of cattle.
AB  - OBJECTIVE: To compare the content of substance P, vasoactive intestinal
      polypeptide, and neurofilament 200 in biopsy specimens taken from the abomasal
      wall of healthy cows of 2 breeds. SAMPLE POPULATION: Biopsy specimens taken from
      different sites of the abomasal wall from 20 German Holstein cows and 20 German
      Fleckvieh cows. PROCEDURES: Biopsy specimens were examined immunohistochemically,
      and the content of substance P, vasoactive intestinal polypeptide, and
      neurofilament 200 was determined by measuring the immunoreactive areas. RESULTS:
      Significant differences between the breeds were detected. Substance P-immuno
      reactive area in the corpus abomasi was significantly smaller in the German
      Holsteins (geometric mean +/- geometric SD, 679 +/- 1.83 microm2) than in the
      German Fleckvieh cows (1,020 +/- 1.65 microm2). Concerning vasoactive intestinal
      polypeptide, differences between breeds were not significant. Overall nerve
      density in the antral abomasal wall was significantly greater in German Holsteins
      than in German Fleckvieh cows (immunoreactive areas for neurofilament 200 in
      German Holsteins was 4,842 +/- 1.29 microm2 and in German Fleckvieh cows was
      3,333 +/- 1.63 microm2). Conclusions and Clinical Relevance-The significantly
      lower content of substance P in the corpus abomasi could explain why German
      Holstein cows are predisposed to abomasal displacement, compared with German
      Fleckvieh cows, in which this disease is a rare finding.

PMID- 18828679
TI  - Effect of inhalation of isoflurane at end-tidal concentrations greater than,
      equal to, and less than the minimum anesthetic concentration on bispectral index
      in chickens.
AB  - OBJECTIVE: To determine the effect of inhalation of isoflurane at end-tidal
      concentrations greater than, equal to, and less than the minimum anesthetic
      concentration (MAC) on bispectral index (BIS) in chickens. Animals-10 chickens.
      PROCEDURES: For each chicken, the individual MAC of isoflurane was determined by
      use of the toe-pinch method. After a 1-week interval, chickens were anesthetized
      with isoflurane at concentrations 1.75, 1.50, 1.25, 1.00, and 0.75 times their
      individual MAC (administered from higher to lower concentrations). At each MAC
      multiple, a toe pinch was performed and BIS was assessed and correlated with
      heart rate, blood pressure, and an awareness score (derived by use of a visual
      analogue scale). RESULTS: Among the chickens, mean +/- SD MAC of isoflurane was
      1.15 +/- 0.20%. Burst suppression was detected at every MAC multiple. The BIS and
      awareness score were correlated directly with each other and changed inversely
      with increasing isoflurane concentration. Median (range) BIS values during
      anesthesia at 1.75, 1.50, 1.25, 1.00, and 0.75 MAC of isoflurane were 25 (15 to
      35), 35 (25 to 45), 35 (20 to 50), 40 (25 to 55), and 50 (35 to 65),
      respectively. Median BIS value at extubation was 70 +/- 9. Values of BIS
      correlated with blood pressure, but not with heart rate. Blood pressure changed
      with end-tidal isoflurane concentrations, whereas heart rate did not. CONCLUSIONS
      AND CLINICAL RELEVANCE: Assessment of BIS can be used to monitor the electrical
      activity of the brain and the degree of unconsciousness in chickens during
      isoflurane anesthesia.

PMID- 18828680
TI  - Respiratory alkalosis and primary hypocapnia in Labrador Retrievers participating
      in field trials in high-ambient-temperature conditions.
AB  - OBJECTIVE: To determine whether Labrador Retrievers participating in field trials
      develop respiratory alkalosis and hypocapnia primarily in conditions of high
      ambient temperatures. ANIMALS: 16 Labrador Retrievers. PROCEDURES: At each of 5
      field trials, 5 to 10 dogs were monitored during a test (retrieval of birds over
      a variable distance on land [1,076 to 2,200 m]; 36 assessments); ambient
      temperatures ranged from 2.2 degrees to 29.4 degrees C. For each dog, rectal
      temperature was measured and a venous blood sample was collected in a heparinized
      syringe within 5 minutes of test completion. Blood samples were analyzed on site
      for Hct; pH; sodium, potassium, ionized calcium, glucose, lactate, bicarbonate,
      and total CO2 concentrations; and values of PvO2 and PvCO2. Scatterplots of each
      variable versus ambient temperature were reviewed. Regression analysis was used
      to evaluate the effect of ambient temperature (< or = 21 degrees C and > 21
      degrees C) on each variable. RESULTS: Compared with findings at ambient
      temperatures < or = 21 degrees C, venous blood pH was increased (mean, 7.521 vs
      7.349) and PvCO2 was decreased (mean, 17.8 vs 29.3 mm Hg) at temperatures > 21
      degrees C; rectal temperature did not differ. Two dogs developed signs of heat
      stress in 1 test at an ambient temperature of 29 degrees C; their rectal
      temperatures were higher and PvCO2 values were lower than findings in other dogs.
      CONCLUSIONS AND CLINICAL RELEVANCE: When running distances frequently encountered
      at field trials, healthy Labrador Retrievers developed hyperthermia regardless of
      ambient temperature. Dogs developed respiratory alkalosis and hypocapnia at
      ambient temperatures > 21 degrees C.

PMID- 18828681
TI  - Hemodynamic and serum biochemical alterations associated with intravenous
      administration of three types of contrast media in anesthetized dogs.
AB  - OBJECTIVE: To determine the incidence and type of alterations in heart rate (HR),
      peak systolic blood pressure (PSBP), and serum biochemical variables (total
      bilirubin, BUN, and creatinine concentrations) associated with IV administration
      of ionic-iodinated contrast (IIC), nonionic-iodinated contrast (NIC), and
      gadolinium dimeglumine (GD) contrast media in anesthetized dogs. ANIMALS: 280
      anesthetized dogs undergoing cross-sectional imaging. PROCEDURES: HR and PSBP
      were recorded at 5-minute intervals for 20 minutes for untreated control dogs and
      dogs that received IIC, NIC, or GD contrast medium. The development of an HR of <
      60 beats/min or > 130 beats/min that included a > or = 20% change from baseline
      was considered a response. The development of PSBP of < 90 mm Hg or > 160 mm Hg
      that included a > or = 20% change from baseline was considered a response. Pre-
      and postcontrast serum biochemical values were recorded. Results-Of dogs
      receiving IIC medium, 3% (3/91) had a response in HR and 4% (4/91) had a response
      in PSBP at > or = 1 time points. None of the dogs receiving NIC medium had a
      response in HR; 1 of 16 had a response in PSBP. Of dogs receiving GD contrast
      medium, 1% (1/92) had a response in HR and 4% (4/92) had a response in PSBP. Of
      control dogs, 2% (2/81) had a response in HR and 4% (3/81) had a response in
      PSBP. No serum biochemical alterations were observed. CONCLUSIONS AND CLINICAL
      RELEVANCE: IV administration of contrast media in anesthetized dogs caused
      moderate bradycardia, tachycardia, hypotension, or hypertension.

PMID- 18828682
TI  - Hemodynamic and serum biochemical alterations associated with intravenous
      administration of three types of contrast media in anesthetized cats.
AB  - OBJECTIVE: To determine the incidence and type of alterations in heart rate (HR),
      peak systolic blood pressure (PSBP), and serum biochemical variables (serum total
      bilirubin, BUN, and creatinine concentrations) associated with IV administration
      of ionic-iodinated contrast (IIC), nonionic-iodinated contrast (NIC), and
      gadolinium (GD) contrast media in anesthetized cats. ANIMALS: 220 anesthetized
      cats undergoing cross-sectional imaging. PROCEDURES: HR and PSBP were recorded at
      5-minute intervals for 20 minutes for untreated control cats and cats that
      received IIC, NIC, or GD contrast medium. The development of HR < 100 beats/min
      or > 200 beats/min that included a > or = 20% change from baseline was considered
      a response. The development of PSBP of < 90 mm Hg or > 170 mm Hg that included a
      > or = 20% change from baseline was considered a response. Pre- and postcontrast
      serum biochemical values were recorded. Results-Of cats receiving IIC medium, 2%
      (1/60) had a response in HR at > or = 1 time point. Of cats receiving IIC medium,
      7% (4/60) had a response in PSBP. None of the cats receiving NIC medium had a
      response in HR; 2 of 12 had a response in PSBP. Of cats receiving GD contrast
      medium, 6% (5/83) had a response in HR and 8% (7/83) had a response in PSBP. None
      of the control cats had a response in HR or PSBP. No serum biochemical
      alterations were observed. CONCLUSIONS AND CLINICAL RELEVANCE: IV administration
      of iodine and GD contrast media in anesthetized cats was associated with changes
      in HR and PSBP.

PMID- 18828683
TI  - Evaluation of lymphocyte apoptosis in dogs with inflammatory bowel disease.
AB  - OBJECTIVE: To determine whether lymphocyte apoptosis in intestinal mucosae is
      more common in healthy dogs than dogs with inflammatory bowel disease (IBD) and
      whether numbers of apoptotic cells increase after successful treatment of
      affected dogs. ANIMALS: 8 dogs with IBD (IBD dogs) and 8 healthy control dogs.
      PROCEDURES: Biopsy specimens of the duodenum and colon were obtained via
      endoscopy from dogs with IBD before and after 10 weeks of standard treatment and
      compared with specimens obtained from control dogs. Expression of activated
      caspase 3 (Casp3), caspase-cleaved fragment p85 from poly-ADP-ribose polymerase
      (PARP), and B-cell leukemia/lymphoma 2 (Bcl-2) was measured in the duodenal
      (villous tip and base) and colonic mucosae. RESULTS: Expression of Casp3 was
      greater in the duodenal villous tips of control dogs, compared with expression in
      similar tissues from dogs with IBD before or after treatment. Despite clinical
      improvement of dogs with IBD, expression of Casp3 did not increase after
      treatment. Expression of PARP did not differ between groups at any time point.
      Expression of Bcl-2 was greater at all 3 tissue sites in control dogs, compared
      with expression at the same sites in dogs with IBD. Furthermore, Bcl-2 expression
      in duodenal villous tips was higher in dogs with IBD after treatment but was not
      higher elsewhere. In control dogs, expression patterns for all 3 markers were
      similar between sites (villous tip > villous base > colon). CONCLUSIONS AND
      CLINICAL RELEVANCE: Expression of Casp3 in lymphocytes in duodenal villous tips
      was significantly reduced in dogs with IBD, compared with expression in healthy
      dogs, but no increase was detected following successful treatment of IBD.
      Increased expression of Bcl-2 may be a potential marker of the success of
      treatment.

PMID- 18828684
TI  - Exploratory spatial data analysis of regional seroprevalence of antibodies
      against epizootic hemorrhagic disease virus in cattle from Illinois and Indiana.
AB  - OBJECTIVE: To estimate seroprevalence of antibodies against the serogroup of
      epizootic hemorrhagic disease viruses (EHDVs) and describe spatial distribution
      of antibodies against EHDV among cattle herds in Illinois and western Indiana.
      SAMPLE POPULATION: 9,414 serum samples collected from cattle in 60 herds over 3
      transmission seasons. PROCEDURES: Serum samples were tested for antibodies
      against EHDV by use of an ELISA. Seroprevalence for 4 zones covering the length
      of Illinois and parts of Indiana were estimated. A multivariable mixed-effects
      logistic regression model with a random effect for herd was used to estimate
      seropositive risk for zone (1 through 4), age (yearling, adult), herd type (beef,
      dairy), transmission season (2000 to 2002), and zone by year interaction.
      Isopleth maps of seroprevalence at the herd level were produced. RESULTS:
      Antibodies against EHDV were detected in 1,110 (11.8%) samples. Estimated
      seroprevalence in 2000, 2001, and 2002 was 15.3%, 13.4%, and 5.2%, respectively.
      Seroprevalence was highest in the southernmost zone and lowest in the
      northernmost zone, but risk of seropositivity for EHDV among and within zones
      varied by year. Clusters of high seroprevalence in the south, low seroprevalence
      in the north, and outliers of high and low seroprevalence were detected. Risk
      mapping revealed areas of higher seroprevalence extending northward along the
      western and eastern ends of the study region. CONCLUSIONS: Seroprevalence of
      antibodies against EHDV in cattle was higher in the south than north; however,
      local complexities existed that were not observed in a serosurvey of antibodies
      against bluetongue virus from the same cattle population.

PMID- 18828685
TI  - Identification of quantitative trait loci for osteoarthritis of hip joints in
      dogs.
AB  - OBJECTIVE: To identify quantitative trait loci (QTL) associated with
      osteoarthritis (OA) of hip joints of dogs by use of a whole-genome microsatellite
      scan. ANIMALS: 116 founder, backcross, F1, and F2 dogs from a crossbred pedigree.
      PROCEDURES: Necropsy scores and an optimized set of 342 microsatellite markers
      were used for interval mapping by means of a combined backcross and F2 design
      module from an online statistical program. Breed and sex were included in the
      model as fixed effects. Age of dog at necropsy and body weight at 8 months of age
      were also included in the model as covariates. The chromosomal location at which
      the highest F score was obtained was considered the best estimate of a QTL
      position. Chromosome-wide significance thresholds were determined empirically
      from 10,000 permutations of marker genotypes. RESULTS: 4 chromosomes contained
      putative QTL for OA of hip joints in dogs at the 5% chromosome-wide significance
      threshold: chromosomes 5, 18, 23, and 31. CONCLUSIONS AND CLINICAL RELEVANCE:
      Osteoarthritis of canine hip joints is a complex disease to which many genes and
      environmental factors contribute. Identification of contributing QTL is a
      strategy to elucidate the genetic mechanisms that underlie this disease.
      Refinement of the putative QTL and subsequent candidate gene studies are needed
      to identify the genes involved in the disease process.

PMID- 18828686
TI  - Evaluation of perinuclear anti-neutrophilic cytoplasmic autoantibodies as an
      early marker of protein-losing enteropathy and protein-losing nephropathy in Soft
      Coated Wheaten Terriers.
AB  - OBJECTIVE: To evaluate perinuclear anti-neutrophilic cytoplasmic autoantibody
      (pANCA) status in Soft Coated Wheaten Terriers (SCWTs) and SCWT-Beagle crossbred
      dogs and to correlate pANCA status of dogs with clinicopathologic variables of
      protein-losing enteropathy (PLE), protein-losing nephropathy (PLN), or both.
      ANIMALS: 13 SCWTs and 8 SCWT-Beagle crossbred dogs in a research colony and a
      control group comprising 7 dogs with X-linked hereditary nephropathy and 12
      healthy SCWTs > 9 years old. PROCEDURES: Samples were obtained from dogs in the
      research colony every 6 months. At each sample-collection time point, serum
      concentrations of albumin, globulin, creatinine, and urea nitrogen; fecal
      concentration of alpha-proteinase inhibitor; and urinary protein-to-creatinine
      ratios were determined and correlated with pANCA status. RESULTS: 20 of 21 dogs
      in the research colony had positive results for pANCAs at a minimum of 2 time
      points, and 18 of 21 dogs had definitive evidence of disease. None of the control
      dogs had positive results for pANCAs. A positive result for pANCAs was
      significantly associated with hypoalbuminemia, and pANCAs preceded the onset of
      hypoalbuminemia on an average of 2.4 years. Sensitivity and specificity for use
      of pANCAs to predict development of PLE or PLN were 0.95 (95% confidence
      interval, 0.72 to 1.00) and 0.8 (95% confidence interval, 0.51 to 0.95),
      respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Most dogs in this study
      affected with PLE, PLN, or both had positive results for pANCAs before
      clinicopathologic evidence of disease was detected. Thus, pANCAs may be useful as
      an early noninvasive test of disease in SCWTs.

PMID- 18828687
TI  - Assessment of impulse duration thresholds for electrical stimulation of muscles
      (chronaxy) in dogs.
AB  - OBJECTIVE: To determine the electrical impulse duration thresholds (chronaxy) for
      maximal motor contraction of various muscles without stimulation of pain fibers
      in dogs. ANIMALS: 10 healthy adult Beagles. PROCEDURES: The dogs were used to
      assess the minimal intensity (rheobase) required to elicit motor contraction of
      11 muscles (5 in the forelimb [supraspinatus, infraspinatus, deltoideus, lateral
      head of the triceps brachii, and extensor carpi radialis], 5 in the hind limb
      [gluteus medius, biceps femoris, semitendinosus, vastus lateralis, and tibialis
      cranialis], and the erector spinae). The rheobase was used to determine the
      chronaxy for each of the 11 muscles in the 10 dogs; chronaxy values were compared
      with those reported for the corresponding muscles in humans. RESULTS: Compared
      with values in humans, chronaxy values for stimulation of AA motor fibers in the
      biceps femoris and semitendinosus muscles and muscles of the more distal portions
      of limbs were lower in dogs. For the other muscles evaluated, chronaxy values did
      not differ between dogs and humans. CONCLUSIONS AND CLINICAL RELEVANCE:
      Application of the dog-specific chronaxy values when performing electrical
      stimulation for strengthening muscles or providing pain relief is likely to
      minimize the pain perceived during treatment in dogs.

PMID- 18828688
TI  - Flow cytometric evaluation of multidrug resistance proteins on grossly normal
      canine nodal lymphocyte membranes.
AB  - OBJECTIVE: To demonstrate efficacy of flow cytometric evaluation of expression
      and activity of P-glycoprotein (P-gp) and multidrug resistance-associated protein
      (MRP) efflux pumps and characterize and correlate their expression and activity
      in grossly normal canine nodal lymphocytes. SAMPLE POPULATION: Nodal lymphocytes
      from 21 clinically normal dogs. PROCEDURES: Pump expression was assessed by use
      of fluorescent-labeled mouse antihuman P-gp (C494) and MRP1 (MRPm6) antibodies
      and expressed as median values (antibody value divided by isotype control value).
      The P-gp and MRP activities were assessed by measuring cellular retention of
      rhodamine 123 and 5(6)-carboxyfluorescein diacetate in the absence and presence
      of inhibitors (verapamil and PSC833 for P-gp, probenecid and MK-571 for MRP).
      Protein activity was expressed as median fluorescence of cells with inhibitors
      divided by that without inhibitors. RESULTS: Expression of P-gp was (mean +/-
      SEM) 50.62 +/- 13.39 (n = 21) and that of MRP was 2.16 +/- 0.25 (13). Functional
      activity was 1.27 +/- 0.06 (n = 21) for P-gp and both inhibitors and 21.85 +/-
      4.09 (21) for MRP and both inhibitors. Function and expression were not
      correlated. CONCLUSIONS AND CLINICAL RELEVANCE: Use of flow cytometry effectively
      assessed P-gp and MRP expression and activity in canine lymphocytes. Optimization
      of the flow cytometric assay was determined for evaluating activity and
      expression of these pumps in canine lymphoid cells. Evaluation of expression or
      activity may offer more meaning when correlated with clinical outcome of dogs
      with lymphoproliferative diseases. Cell overexpression of P-gp and MRP can convey
      drug resistance.

PMID- 18828689
TI  - Oral bioavailability of etoposide after administration of a single dose to tumor
      bearing dogs.
AB  - OBJECTIVE: To characterize oral bioavailability and pharmacokinetic disposition
      of etoposide when the IV formulation was administered orally to dogs. ANIMALS: 8
      tumor-bearing dogs. PROCEDURES: An open-label, single-dose, 2-way crossover study
      was conducted. Dogs were randomly assigned to initially receive a single dose of
      etoposide (50 mg/m2) IV or PO. A second dose was administered via the alternate
      route 3 to 7 days later. Medications were administered before IV administration
      of etoposide to prevent hypersensitivity reactions. Oral administration of
      etoposide was prepared by reconstituting the parenteral formulation with 0.9%
      NaCl solution and further diluting the reconstituted mixture 1:1 with a
      sweetening agent. Plasma samples were obtained after both treatments. Etoposide
      concentrations were measured with a high-performance liquid chromatography assay,
      and plasma etoposide concentration-time profiles were analyzed by use of
      noncompartmental methods. RESULTS: 4 dogs had hypersensitivity reactions during
      IV administration of etoposide. No adverse effects were detected after oral
      administration. Plasma etoposide concentrations were undetectable in 2 dogs after
      oral administration. Oral administration of etoposide resulted in significantly
      lower values for the maximum plasma concentration and the area under the plasma
      etoposide concentration-versus-time curve, compared with results for IV
      administration. Oral bioavailability of etoposide was low (median, 13.4%) and
      highly variable among dogs (range, 5.7% to 57.3%). CONCLUSIONS AND CLINICAL
      RELEVANCE-Vehicle-related toxicosis can limit the IV administration of etoposide
      in dogs. The parenteral formulation of etoposide can be safely administered
      orally to dogs, but routine use was not supported because of low and variable
      oral bioavailability in this study.

PMID- 18828690
TI  - Novel variations and loss of heterozygosity of BRCA2 identified in a dog with
      mammary tumors.
AB  - OBJECTIVE: To establish novel polymorphic markers for analysis of loss of
      heterozygosity (LOH), so as to study the possible involvement of BRCA2 in mammary
      tumors obtained from dogs. SAMPLE POPULATION: Blood samples, mammary gland
      specimens, or mammary tumors from 3 tumor-bearing dogs and 10 tumor-free dogs.
      PROCEDURES: Nucleotide sequence analysis was performed with a DNA autosequencer.
      Loss of heterozygosity analysis was performed for markers established in the
      present study. The expression level of canine BRCA2 was quantified by real-time
      PCR analysis. RESULTS: 3 novel microsatellite markers with high heterozygosity
      rates (> 50%) were established, and the previously reported marker for canine
      BRCA2 gene locus was improved. These markers were used for the analysis of DNA
      from formalin-fixed and paraffin-embedded samples. By use of these markers, LOH
      in canine BRCA2 was identified as a result of recombination. In mammary tumor DNA
      that corresponded to the LOH-positive dog, the level of canine BRCA2 expression
      was decreased compared with that of nonneoplastic mammary gland tissue; the open
      reading frame contained 4 missense variations, 1 insertion variation, and 1
      silent variation, some of which were localized to functional domains. CONCLUSIONS
      AND CLINICAL RELEVANCE: 3 novel polymorphic markers were developed for LOH
      analysis of canine BRCA2 and identified a dog with LOH with some variations in
      the functional domains. These markers could be useful for assessing the relevance
      of BRCA2 variation in mammary tumors of dogs.

PMID- 18828691
TI  - Role of bacteria in the pathogenesis of recurrent uveitis in horses from the
      southeastern United States.
AB  - OBJECTIVE: To determine the role of intraocular bacteria in the pathogenesis of
      equine recurrent uveitis (ERU) in horses from the southeastern United States by
      evaluating affected eyes of horses with ERU for bacterial DNA and intraocular
      production of antibodies against Leptospira spp. SAMPLE POPULATION: Aqueous
      humor, vitreous humor, and serum samples of 24 clinically normal horses, 52
      horses with ERU, and 17 horses with ocular inflammation not associated with ERU
      (ie, non-ERU inflammation). PROCEDURES: Ribosomal RNA quantitative PCR (real-time
      PCR) assay was used to detect bacterial DNA in aqueous humor and vitreous humor
      from clinically normal horses (n = 12) and horses with chronic (> 3-month) ERU
      (28). Aqueous humor and serum were also evaluated for anti-Leptospira antibody
      titers from clinically normal horses (n = 12), horses with non-ERU inflammation
      (17), and horses with confirmed chronic ERU (24). RESULTS: Bacterial DNA was not
      detected in aqueous humor or vitreous humor of horses with ERU or clinically
      normal horses. No significant difference was found in titers of anti-Leptospira
      antibodies in serum or aqueous humor among these 3 groups. Only 2 horses, 1 horse
      with ERU and 1 horse with non-ERU inflammation, had definitive intraocular
      production of antibodies against Leptospira organisms. CONCLUSIONS AND CLINICAL
      RELEVANCE: In horses from the southeastern United States, Leptospira organisms
      may have helped initiate ERU in some, but the continued presence of the organisms
      did not play a direct role in the pathogenesis of this recurrent disease.

PMID- 18828692
TI  - Characterization and prevalence of cataracts in Labrador Retrievers in The
      Netherlands.
AB  - OBJECTIVE: To assess the prevalence and distribution of types of cataract,
      investigate the effects of selective breeding on cataract development, and
      identify the relationship between posterior polar cataract and other types of
      cortical cataracts in Labrador Retrievers in The Netherlands. ANIMALS: 9,017
      Labrador Retrievers. PROCEDURES: Records of 18,283 ophthalmic examinations
      performed by veterinary ophthalmologists from 1977 through 2005 were reviewed.
      There were 522 dogs affected by hereditary cataracts in 1 or both eyes without
      progressive retinal atrophy (PRA) and 166 PRA-affected dogs with cataracts. These
      cataracts were divided into 3 groups: posterior polar (triangular) cataract,
      extensive immature and mature cataract, and a miscellaneous group. Dogs with PRA
      were analyzed separately. RESULTS: From 1980 through 2000, the prevalence of
      hereditary cataracts was stable at 8%. The prevalence of cataracts in offspring
      of cataract-affected dogs was significantly increased, compared with the
      prevalence in offspring of nonaffected dogs. The distribution of types of
      cataract was significantly different between dogs with primary cataracts and PRA
      affected dogs. Dogs with posterior polar (triangular) cataracts produced affected
      offspring with the same distribution of types of cataracts as the entire
      population of primary cataract-affected dogs. CONCLUSIONS AND CLINICAL RELEVANCE:
      Cataract development in the Labrador Retriever population in The Netherlands
      appears to be a predominantly genetic disorder. Posterior polar (triangular)
      cataracts appear to be related to other types of hereditary cataract. Although
      there is no conclusive evidence, it seems valid to continue exclusion of all
      Labrador Retrievers affected by any type of primary cataract from breeding.

PMID- 18828693
TI  - Evaluation of matrix metalloproteinase concentrations in precorneal tear film
      from dogs with Pseudomonas aeruginosa-associated keratitis.
AB  - OBJECTIVE: To evaluate the changes in concentrations of matrix metalloproteinase
      (MMP)-2 and MMP-9 in the precorneal tear film of dogs with Pseudomonas aeruginosa
      associated keratitis during corneal healing and stromal remodeling. ANIMALS: 10
      dogs with unilateral P aeruginosa-associated keratitis and 10 clinically normal
      dogs. PROCEDURES: Precorneal tear film samples were collected from both eyes of
      10 dogs with unilateral P aeruginosa-associated keratitis on the day of admission
      to the hospital and then at various time points until complete healing of the
      cornea was achieved. Precorneal tear film samples were also collected from both
      eyes of 10 clinically normal adult dogs (control group). Concentrations of MMP-2
      and MMP-9 in precorneal tear film samples from each group were determined via
      gelatin zymography for comparison. RESULTS: The proteolytic processes in the
      ulcerated eyes decreased as corneal healing progressed. On the day of admission,
      concentrations of latent and active forms of MMP-2 and MMP-9 in ulcerated eyes
      were significantly higher than values in the contralateral unaffected eyes in
      dogs with P aeruginosa-associated keratitis; concentrations of latent MMP-2 and
      MMP-9 were also greater than control group values. Concentrations of latent and
      active forms of MMP-2 and MMP-9 in the healed eyes of dogs with P aeruginosa
      associated keratitis were significantly lower than concentrations in the
      ulcerated eyes on the day of admission. CONCLUSIONS AND CLINICAL RELEVANCE:
      Results suggest that reduction of precorneal tear film concentrations of MMPs by
      use of proteinase inhibitors may be effective in the treatment of dogs with P
      aeruginosa-associated keratitis.

PMID- 18828694
TI  - Effects of intravenous administration of two volumes of calcium solution on
      plasma ionized calcium concentration and recovery from naturally occurring
      hypocalcemia in lactating dairy cows.
AB  - OBJECTIVE: To compare the effects of administration of 2 volumes of a calcium
      solution (calcium oxide and calcium gluconate) on plasma ionized calcium
      concentration (PICaC) and clinical recovery from naturally occurring hypocalcemia
      (NOHC; milk fever) in lactating dairy cows. ANIMALS: 123 cows with NOHC (PICaC <
      0.95 mmol/L [3.81 mg/dL]) and 20 clinically normal control cows. PROCEDURES:
      Affected cows were treated IV once or repeatedly with 450 (n = 56) or 750 mL (67)
      of calcium solution (1.65 g of calcium/100 mL) until clinical recovery was
      achieved. The PICaC was assessed 48 hours after the first treatment or after the
      treatment that achieved clinical recovery. Biochemical recovery was defined as
      PICaC > or = 0.95 mmol/L. Plasma from control cows was used for PICaC reference
      range determination. Plasma samples from both groups were assessed after storage
      for 20 days at 20 degrees C. RESULTS: The PICaC reference range derived from
      blood collected in tubes containing lithium heparin was 1.02 to 1.29 mmol/L (4.09
      to 5.17 mg/dL). Following storage, plasma samples were suitable for PICaC
      assessment. All cows treated with > or = 1 volume of 450 and 750 mL of calcium
      solution recovered clinically; however, 31 of 83 (37%) evaluated cows were not
      biochemically recovered at 48 hours following treatment. Only cows with PICaC <
      0.48 mmol/L (1.92 mg/dL) before the first treatment had to be treated > or = 3
      times. CONCLUSIONS AND CLINICAL RELEVANCE: Results did not support the need to
      increase the administered volume of calcium solution from 450 to 750 mL for
      treatment of NOHC in dairy cows.

PMID- 18828695
TI  - Evaluation of the efficacy and safety for use of two sedation and analgesia
      protocols to facilitate assisted ventilation of healthy dogs.
AB  - OBJECTIVE: To determine the effectiveness and safety of 2 sedative-analgesic
      protocols to facilitate assisted ventilation in healthy dogs. ANIMALS: 12 healthy
      dogs. PROCEDURES: Dogs were randomly assigned to 2 groups. Mean dosages for
      protocol 1 were diazepam (0.5 mg/kg/h [n = 3 dogs]) or midazolam (0.5 mg/kg/h
      [3]), morphine (0.6 mg/kg/h [6]), and medetomidine (1.0 microg/kg/h [6]). Mean
      dosages for protocol 2 were diazepam (0.5 mg/kg/h [n = 3]) or midazolam (0.5
      mg/kg/h [3]), fentanyl (18 microg/kg/h [6]), and propofol (2.5 mg/kg/h [6]). Each
      dog received the drugs for 24 consecutive hours. All dogs were mechanically
      ventilated with adjustments in minute volume to maintain normocapnia and
      normoxemia. Cardiorespiratory variables were recorded. A numeric comfort score
      was assigned hourly to assess efficacy. Mouth care, position change, and
      physiotherapy were performed every 6 hours. Urine output was measured every 4
      hours. RESULTS: Use of both protocols maintained dogs within optimal comfort
      ranges > 85% of the time. The first dog in each group was excluded from the
      study. Significant decreases in heart rate, oxygen consumption, and oxygen
      extraction ratio were evident for protocol 1. Cardiac index values in ventilated
      dogs were lower than values reported for healthy unsedated dogs. Oxygen delivery,
      lactate concentration, and arterial base excess remained within reference ranges
      for both protocols. CONCLUSIONS AND CLINICAL RELEVANCE: Use of both protocols was
      effective for facilitating mechanical ventilation. A reduction in cardiac index
      was detected for both protocols as a result of bradycardia. However, oxygen
      delivery and global tissue perfusion were not negatively affected.

PMID- 18828696
TI  - Safety and efficacy of an ocular insert for apomorphine-induced emesis in dogs.
AB  - OBJECTIVE: To evaluate the safety and efficacy of an ocular insert designed to
      provide controlled release of apomorphine for the induction of emesis in dogs.
      ANIMALS: 5,001 dogs treated with ocular apomorphine inserts and 32 dogs treated
      with IV administration of apomorphine. PROCEDURES: Data collected on a case
      report form included breed, body weight, time to emesis after placement of the
      insert, and any information available regarding the nature of the toxicosis and
      clinical signs. A list of potential adverse effects was provided, and attending
      clinicians graded their occurrence by use of a subjective scale. Similar report
      forms were used for dogs that received apomorphine IV. Treatment was considered
      successful if emesis occurred within 15 minutes of administration. Safety was
      assessed by evaluation of the frequency and severity of adverse effects. RESULTS:
      For the ocular insert and IV injection groups, the success rates were 83.5% and
      90.6% respectively, and were not significantly different. Adverse effects were
      more frequent in the IV group, whereas ocular irritation was most frequent in the
      insert group. CONCLUSIONS AND CLINICAL RELEVANCE: Overall, the ocular inserts
      provided an alternative to parenteral administration of apomorphine with
      comparable efficacy and a lower prevalence of adverse effects.

PMID- 18828697
TI  - Development of a contagious ecthyma vaccine for goats.
AB  - OBJECTIVE: To identify a strain of contagious ecthyma virus from goats that
      possesses the appropriate characteristics for an effective vaccine for goats.
      ANIMALS: 25 goat kids used for vaccine development and 100 goat kids used for
      evaluation of vaccine efficacy. PROCEDURES: 5 strains of contagious ecthyma virus
      were tested in a vaccination-challenge study to identify the best strain to be
      the seed strain for a contagious ecthyma vaccine. The vaccine derived from the
      chosen viral stain was tested at 2 concentrations for efficacy in a vaccination
      challenge study. RESULTS: 2 of 5 viral strains induced moderate to severe scabs
      following infection, and 3 viral strains protected the goats from wild-type virus
      challenge following vaccination. Viral strain 47CE was selected as the seed
      source for the production of a contagious ecthyma vaccine because of the larger
      vaccine-to-challenge scab formation ratio. Vaccine 47CE protected all goat kids
      (48/48) following challenge with the wild-type contagious ecthyma virus; all goat
      kids (32/32) in the control group had scab formation following challenge with the
      wild-type contagious ecthyma virus, which indicated no protection following
      administration of vaccine diluent. CONCLUSIONS AND CLINICAL RELEVANCE: A vaccine
      containing a caprine strain of contagious ecthyma virus used in goats appeared to
      provide the characteristics needed for an effective vaccine, including good scab
      production and protection from wild-type infection. This vaccine may potentially
      provide better protection for goats from contagious ecthyma than currently
      available vaccines labeled for sheep.

PMID- 18828699
TI  - Introduction: traumatic brain injury.

PMID- 18828700
TI  - Continuous monitoring of cerebrovascular pressure reactivity in patients with
      head injury.
AB  - OBJECT: Cerebrovascular pressure reactivity is the ability of cerebral vessels to
      respond to changes in transmural pressure. A cerebrovascular pressure reactivity
      index (PRx) can be determined as the moving correlation coefficient between mean
      intracranial pressure (ICP) and mean arterial blood pressure. METHODS: The
      authors analyzed a database consisting of 398 patients with head injuries who
      underwent continuous monitoring of cerebrovascular pressure reactivity. In 298
      patients, the PRx was compared with a transcranial Doppler ultrasonography
      assessment of cerebrovascular autoregulation (the mean index [Mx]), in 17
      patients with the PET-assessed static rate of autoregulation, and in 22 patients
      with the cerebral metabolic rate for O(2). Patient outcome was assessed 6 months
      after injury. RESULTS: There was a positive and significant association between
      the PRx and Mx (R(2) = 0.36, p < 0.001) and with the static rate of
      autoregulation (R(2) = 0.31, p = 0.02). A PRx > 0.35 was associated with a high
      mortality rate (> 50%). The PRx showed significant deterioration in refractory
      intracranial hypertension, was correlated with outcome, and was able to
      differentiate patients with good outcome, moderate disability, severe disability,
      and death. The graph of PRx compared with cerebral perfusion pressure (CPP)
      indicated a U-shaped curve, suggesting that too low and too high CPP was
      associated with a disturbance in pressure reactivity. Such an optimal CPP was
      confirmed in individual cases and a greater difference between current and
      optimal CPP was associated with worse outcome (for patients who, on average, were
      treated below optimal CPP [R(2) = 0.53, p < 0.001] and for patients whose mean
      CPP was above optimal CPP [R(2) = -0.40, p < 0.05]). Following decompressive
      craniectomy, pressure reactivity initially worsened (median -0.03 [interquartile
      range -0.13 to 0.06] to 0.14 [interquartile range 0.12-0.22]; p < 0.01) and
      improved in the later postoperative course. After therapeutic hypothermia, in 17
      (70.8%) of 24 patients in whom rewarming exceeded the brain temperature threshold
      of 37 degrees C, ICP remained stable, but the average PRx increased to 0.32 (p <
      0.0001), indicating significant derangement in cerebrovascular reactivity.
      CONCLUSIONS: The PRx is a secondary index derived from changes in ICP and
      arterial blood pressure and can be used as a surrogate marker of cerebrovascular
      impairment. In view of an autoregulation-guided CPP therapy, a continuous
      determination of a PRx is feasible, but its value has to be evaluated in a
      prospective controlled trial.

PMID- 18828701
TI  - Levetiracetam versus phenytoin for seizure prophylaxis in severe traumatic brain
      injury.
AB  - OBJECT: Current standard of care for patients with severe traumatic brain injury
      (TBI) is prophylactic treatment with phenytoin for 7 days to decrease the risk of
      early posttraumatic seizures. Phenytoin alters drug metabolism, induces fever,
      and requires therapeutic-level monitoring. Alternatively, levetiracetam (Keppra)
      does not require serum monitoring or have significant pharmacokinetic
      interactions. In the current study, the authors compare the EEG findings in
      patients receiving phenytoin with those receiving levetiracetam monotherapy for
      seizure prophylaxis following severe TBI. METHODS: Data were prospectively
      collected in 32 cases in which patients received levetiracetam for the first 7
      days after severe TBI and compared with data from a historical cohort of 41 cases
      in which patients received phenytoin monotherapy. Patients underwent 1-hour
      electroencephalographic (EEG) monitoring if they displayed persistent coma,
      decreased mental status, or clinical signs of seizures. The EEG results were
      grouped into normal and abnormal findings, with abnormal EEG findings further
      categorized as seizure activity or seizure tendency. RESULTS: Fifteen of 32
      patients in the levetiracetam group warranted EEG monitoring. In 7 of these 15
      cases the results were normal and in 8 abnormal; 1 patient had seizure activity,
      whereas 7 had seizure tendency. Twelve of 41 patients in the phenytoin group
      received EEG monitoring, with all results being normal. Patients treated with
      levetiracetam and phenytoin had equivalent incidence of seizure activity (p =
      0.556). Patients receiving levetiracetam had a higher incidence of abnormal EEG
      findings (p = 0.003). CONCLUSIONS: Levetiracetam is as effective as phenytoin in
      preventing early posttraumatic seizures but is associated with an increased
      seizure tendency on EEG analysis.

PMID- 18828702
TI  - Acute clinical grading in pediatric severe traumatic brain injury and its
      association with subsequent intracranial pressure, cerebral perfusion pressure,
      and brain oxygenation.
AB  - OBJECT: The goal of this paper was to examine the relationship between methods of
      acute clinical assessment and measures of secondary cerebral insults in severe
      traumatic brain injury in children. METHODS: Patients who underwent intracranial
      pressure (ICP), cerebral perfusion pressure (CPP), and brain oxygenation
      (PbtO(2)) monitoring and who had an initial Glasgow Coma Scale score, Pediatric
      Trauma Score, Pediatric Index of Mortality 2 score, and CT classification were
      evaluated. The relationship between these acute clinical scores and secondary
      cerebral insult measures, including ICP, CPP, PbtO(2), and systemic hypoxia were
      evaluated using univariate and multivariate analysis. RESULTS: The authors found
      significant associations between individual acute clinical scores and select
      physiological markers of secondary injury. However, there was a large amount of
      variability in these results, and none of the scores evaluated predicted each and
      every insult. Furthermore, a number of physiological measures were not predicted
      by any of the scores. CONCLUSIONS: Although they may guide initial treatment,
      grading systems used to classify initial injury severity appear to have a limited
      value in predicting who is at risk for secondary cerebral insults.

PMID- 18828698
TI  - Regulation of NADPH oxidase in vascular endothelium: the role of phospholipases,
      protein kinases, and cytoskeletal proteins.
AB  - The generation of reactive oxygen species (ROS) in the vasculature plays a major
      role in the genesis of endothelial cell (EC) activation and barrier function. Of
      the several potential sources of ROS in the vasculature, the endothelial NADPH
      oxidase family of proteins is a major contributor of ROS associated with lung
      inflammation, ischemia/reperfusion injury, sepsis, hyperoxia, and ventilator
      associated lung injury. The NADPH oxidase in lung ECs has most of the components
      found in phagocytic oxidase, and recent studies show the expression of several
      homologues of Nox proteins in vascular cells. Activation of NADPH oxidase of
      nonphagocytic vascular cells is complex and involves assembly of the cytosolic
      (p47(phox), p67(phox), and Rac1) and membrane-associated components (Noxes and
      p22(phox)). Signaling pathways leading to NADPH oxidase activation are not
      completely defined; however, they do appear to involve the cytoskeleton and
      posttranslation modification of the components regulated by protein kinases,
      protein phosphatases, and phospholipases. Furthermore, several key components
      regulating NADPH oxidase recruitment, assembly, and activation are enriched in
      lipid microdomains to form a functional signaling platform. Future studies on
      temporal and spatial localization of Nox isoforms will provide new insights into
      the role of NADPH oxidase-derived ROS in the pathobiology of lung diseases.

PMID- 18828703
TI  - Prehospital management of traumatic brain injury.
AB  - The aim of this study was to review the current protocols of prehospital practice
      and their impact on outcome in the management of traumatic brain injury. A
      literature review of the National Library of Medicine encompassing the years 1980
      to May 2008 was performed. The primary impact of a head injury sets in motion a
      cascade of secondary events that can worsen neurological injury and outcome. The
      goals of care during prehospital triage, stabilization, and transport are to
      recognize life-threatening raised intracranial pressure and to circumvent
      cerebral herniation. In that process, prevention of secondary injury and
      secondary insults is a major determinant of both short- and longterm outcome.
      Management of brain oxygenation, blood pressure, cerebral perfusion pressure, and
      raised intracranial pressure in the prehospital setting are discussed. Patient
      outcomes are dependent upon an organized trauma response system. Dispatch and
      transport timing, field stabilization, modes of transport, and destination levels
      of care are addressed. In addition, special considerations for mass casualty and
      disaster planning are outlined and recommendations are made regarding early
      response efforts and the ethical impact of aggressive prehospital resuscitation.
      The most sophisticated of emergency, operative, or intensive care units cannot
      reverse damage that has been set in motion by suboptimal protocols of triage and
      resuscitation, either at the injury scene or en route to the hospital. The
      quality of prehospital care is a major determinant of long-term outcome for
      patients with traumatic brain injury.

PMID- 18828704
TI  - Molecular mechanisms of traumatic brain injury in children. A review.
AB  - Despite advances in molecular biology and genetics, the precise pathophysiology
      of traumatic brain injury (TBI) in children is unknown. In this paper the authors
      review what is currently known about intra- and extracellular responses to
      pediatric TBI and relate these factors to future investigations. Although
      hyperemia and vascular congestion have long been thought to be the hallmarks of
      pediatric TBI, on a cellular level, calcium influx as well as modulation of local
      neurotransmitters appears to play a major role in its onset. Recent genetic and
      proteomic research has identified specific neurotrophic factors as well as
      apoptotic and antiapoptotic genes that appear to control the progression of
      inflammation and neuronal damage. The search for a therapeutic target will
      ultimately require a thorough understanding of these factors and their interplay
      on a proteomic, genomic, and neuromic level.

PMID- 18828705
TI  - Cerebral pressure autoregulation in traumatic brain injury.
AB  - An understanding of normal cerebral autoregulation and its response to
      pathological derangements is helpful in the diagnosis, monitoring, management,
      and prognosis of severe traumatic brain injury (TBI). Pressure autoregulation is
      the most common approach in testing the effects of mean arterial blood pressure
      on cerebral blood flow. A gold standard for measuring cerebral pressure
      autoregulation is not available, and the literature shows considerable disparity
      in methods. This fact is not surprising given that cerebral autoregulation is
      more a concept than a physically measurable entity. Alterations in cerebral
      autoregulation can vary from patient to patient and over time and are critical
      during the first 4-5 days after injury. An assessment of cerebral autoregulation
      as part of bedside neuromonitoring in the neurointensive care unit can allow the
      individualized treatment of secondary injury in a patient with severe TBI. The
      assessment of cerebral autoregulation is best achieved with dynamic
      autoregulation methods. Hyperventilation, hyperoxia, nitric oxide and its
      derivates, and erythropoietin are some of the therapies that can be helpful in
      managing cerebral autoregulation. In this review the authors summarize the most
      important points related to cerebral pressure autoregulation in TBI as applied in
      clinical practice, based on the literature as well as their own experience.

PMID- 18828706
TI  - Beta blockers exposure and traumatic brain injury: a literature review.
AB  - Traumatic brain injury (TBI) continues to carry a significant public health
      burden and is anticipated to worsen worldwide over the next century. Recently the
      authors of several articles have suggested that exposure to beta blockers may
      improve mortality rates following TBI. The exact mechanism through which beta
      blockers mediate this effect is unknown. In this paper, the authors review the
      literature regarding the safety of beta blockers in patients with TBI. The
      findings of several recent retrospective cohort studies are examined and
      implications for future investigation are discussed. Future questions to be
      addressed include: the specific indications for the use of beta blockers in
      patients with TBI, the optimal type and dose of beta blocker given, the end point
      of beta blocker therapy, and the safety of beta blockers in cases of severe TBIs.

PMID- 18828707
TI  - A review of selective hypothermia in the management of traumatic brain injury.
AB  - OBJECT: Traumatic brain injury (TBI) remains a significant cause of morbidity and
      death in the US and worldwide. Resuscitative systemic hypothermia following TBI
      has been established as an effective neuroprotective treatment in multiple
      studies in animals and humans, although this intervention carries with it a
      significant risk profile as well. Selective, or preferential, methods of inducing
      cerebral hypothermia have taken precedence over the past few years in order to
      minimize systemic adverse effects. In this report, the authors explore the
      current methods available for inducing selective cerebral hypothermia following
      TBI and review the literature regarding the results of animal and human trials in
      which these methods have been implemented. METHODS: A search of the PubMed
      archive (National Library of Medicine) and the reference lists of all relevant
      articles was conducted to identify all animal and human studies pertaining to the
      use of selective brain cooling, selective hypothermia, preferential hypothermia,
      or regional hypothermia following TBI. RESULTS: Multiple methods of inducing
      selective cerebral hypothermia are currently in the experimental phases,
      including surface cooling, intranasal selective hypothermia, transarterial or
      transvenous endovascular cooling, extraluminal vascular cooling, and epidural
      cerebral cooling. CONCLUSIONS: Several methods of conferring preferential
      neuroprotection via selective hypothermia currently are being tested. Class I
      prospective clinical trials are required to assess the safety and efficacy of
      these methods.

PMID- 18828708
TI  - Regulation of autophagy by reactive oxygen species (ROS): implications for cancer
      progression and treatment.
AB  - Reactive oxygen species (ROS) have been identified as signaling molecules in
      various pathways regulating both cell survival and cell death. Autophagy, a self
      digestion process that degrades intracellular structures in response to stress,
      such as nutrient starvation, is also involved in both cell survival and cell
      death. Alterations in both ROS and autophagy regulation contribute to cancer
      initiation and progression, and both are targets for developing therapies to
      induce cell death selectively in cancer cells. Many stimuli that induce ROS
      generation also induce autophagy, including nutrient starvation, mitochondrial
      toxins, hypoxia, and oxidative stress. Some of these stimuli are under clinical
      investigation as cancer treatments, such as 2-methoxyestrodial and arsenic
      trioxide. Recently, it was demonstrated that ROS can induce autophagy through
      several distinct mechanisms involving Atg4, catalase, and the mitochondrial
      electron transport chain (mETC). This leads to both cell-survival and cell-death
      responses and could be selective toward cancer cells. In this review, we give an
      overview of the roles ROS and autophagy play in cell survival and cell death, and
      their importance to cancer. Furthermore, we describe how autophagy is mediated by
      ROS and the implications of this regulation to cancer treatments.

PMID- 18828712
TI  - Concerned about increasing veterinary technician shortage.

PMID- 18828709
TI  - Hydrodynamic limb vein injection of adeno-associated virus serotype 8 vector
      carrying canine myostatin propeptide gene into normal dogs enhances muscle
      growth.
AB  - Inhibition or blockade of myostatin, a negative growth factor of skeletal muscle,
      enhances muscle growth and therefore is considered a promising strategy for the
      treatment of muscle-wasting diseases such as the muscular dystrophies.
      Previously, we showed that myostatin blockade in both normal and dystrophin
      deficient mdx mice by systemic delivery of the myostatin propeptide (MPRO) gene
      by an adeno-associated virus serotype 8 (AAV8) vector could enhance muscle growth
      and ameliorate dystrophic lesions. Here, we further investigate whether the
      muscle growth effect of myostatin blockade can be achieved in dogs by gene
      transfer. First, we cloned the canine MPRO gene, packaged it in the AAV8 vector,
      and showed robust muscle-enhancing effects after systemic delivery into neonatal
      mice. This vector was then further tested in two 3-month-old normal dogs
      (weighing 9.7 and 6.3 kg). The vector was delivered to one limb by hydrodynamic
      vein injection, and the contralateral limb served as a control. The delivery
      procedure was safe, without discernible adverse effects. AAV vector DNA and MPRO
      gene expression were detected by quantitative polymerase chain reaction, Western
      blotting, and immunofluorescence staining of muscle biopsies. Overexpression of
      MPRO resulted in enhanced muscle growth without a cytotoxic T lymphocytic immune
      response, as evidenced by larger myofibers in multiple muscles, increased muscle
      volume determined by magnetic resonance imaging, and the lack of CD4+ and CD8+ T
      cell infiltration in the vector-injected limbs. Our preliminary study thus
      supports further investigation of this therapeutic strategy in the dystrophin
      deficient golden retriever muscular dystrophy dog model.

PMID- 18828713
TI  - What is your diagnosis? Benign true cementoma (benign cementoblastoma).

PMID- 18828714
TI  - Employment, starting salaries, and educational indebtedness of year-2008
      graduates of US veterinary medical schools and colleges.

PMID- 18828715
TI  - A focus group study of veterinarians' and pet owners' perceptions of veterinarian
      client communication in companion animal practice.
AB  - OBJECTIVE: To compare veterinarians' and pet owners' perceptions of client
      expectations with respect to veterinarian-client communication and to identify
      related barriers and challenges to communication. DESIGN: Qualitative study based
      on focus group interviews. PARTICIPANTS: 6 pet owner focus groups (32 owners) and
      4 veterinarian focus groups (24 companion animal veterinarians). PROCEDURES:
      Independent focus group sessions were conducted with standardized open-ended
      questions and follow-up probes. Content analysis was performed on transcripts of
      the focus group discussions. RESULTS: Five themes related to veterinarian-client
      communication were identified: educating clients (ie, explaining important
      information, providing information up front, and providing information in various
      forms), providing choices (ie, providing pet owners with a range of options,
      being respectful of owners' decisions, and working in partnership with owners),
      using 2-way communication (ie, using language clients understand, listening to
      what clients have to say, and asking the right questions), breakdowns in
      communication that affected the client's experience (ie, owners feeling
      misinformed, that they had not been given all options, and that their concerns
      had not been heard), and challenges veterinarians encountered when communicating
      with clients (ie, monetary concerns, client misinformation, involvement of > 1
      client, and time limitations). CONCLUSIONS: Results suggested that several
      factors are involved in providing effective veterinarian-client communication and
      that breakdowns in communication can have an adverse effect on the veterinarian
      client relationship.

PMID- 18828716
TI  - How changes affecting wholesale drug distribution can impact veterinary
      practitioners.

PMID- 18828717
TI  - Microbial culture of blood samples and serologic testing for bartonellosis in
      cats with chronic rhinosinusitis.
AB  - OBJECTIVE: To assess the role of Bartonella spp in chronic rhinosinusitis (CRS)
      by determining detection rates for the organism by serologic testing and
      microbial culture of blood samples for Bartonella spp in cats with CRS and
      control cats (cats with other nasal diseases, cats with systemic illnesses, and
      healthy cats). DESIGN: Prospective case-control study. ANIMALS: 19 cats with CRS,
      10 cats with other nasal diseases, 15 cats with systemic illness, and 15 healthy
      cats. Procedures-Serologic testing for Bartonella clarridgeiae and Bartonella
      henselae and microbial culture of blood samples were conducted in all cats. In
      cats with CRS and cats with other nasal diseases, a nasal biopsy specimen was
      submitted, when available, for tissue PCR assay to detect Bartonella spp.
      RESULTS: 9 of 19 cats with CRS had positive results for serologic testing for 1
      or both Bartonella spp; whereas, 4 of 10 cats with other nasal diseases, 2 of 15
      cats with systemic diseases, and 4 of 15 healthy cats had positive results for
      serologic testing to detect Bartonella spp. These values did not differ
      significantly among groups. Microbial culture of blood samples yielded B henselae
      in 1 cat with a nasopharyngeal abscess. The PCR assay for Bartonella spp in nasal
      tissues yielded negative results for 9 of 9 cats with CRS and 5 of 5 cats with
      other nasal diseases. CONCLUSIONS AND CLINICAL RELEVANCE: A role for Bartonella
      spp in the pathogenesis of CRS in cats was not supported by results of this
      study.

PMID- 18828719
TI  - Quantification of the association between intervertebral disk calcification and
      disk herniation in Dachshunds.
AB  - OBJECTIVE: To quantify the association between intervertebral disk calcification
      and disk herniation in Dachshunds. DESIGN: Longitudinal study. ANIMALS: 61
      Dachshunds that had been radiographically screened for calcification of
      intervertebral disks at 2 years of age in other studies. Thirty-seven of the dogs
      had survived to the time of the present study and were > or = 8 years of age; 24
      others had not survived. PROCEDURES: Radiographic examination of 36 surviving
      dogs was performed, and information on occurrence of disk calcification at 2
      years of age were obtained from records of all 61 Dachshunds. Information on
      occurrence of disk herniation between 2 and 8 years of age was obtained from
      owners via questionnaire. Associations between numbers of calcified disks and
      disk herniation were analyzed via maximum likelihood logistic regression.
      RESULTS: Disk calcification at 2 years of age was a significant predictor of
      clinical disk herniation (odds ratio per calcified disk, 1.42; 95% confidence
      interval, 1.19 to 1.81). Number of calcified disks in the full vertebral column
      was a better predictor than number of calcified disks between vertebrae T10 and
      L3. Numbers of calcified disks at > or = 8 years of age and at 2 years of age
      were significantly correlated. CONCLUSIONS AND CLINICAL RELEVANCE: Number of
      calcified disks at 2 years of age was a good predictor of clinical disk
      herniation in Dachshunds. Because of the high heritability of disk calcification,
      it is possible that an effective reduction in occurrence of severe disk
      herniation in Dachshunds could be obtained by selective breeding against high
      numbers of calcified disks at 2 years of age.

PMID- 18828720
TI  - Results of the confidential enquiry into perioperative small animal fatalities
      regarding risk factors for anesthetic-related death in dogs.
AB  - OBJECTIVE: To identify major risk factors associated with anesthetic-related
      death in dogs. DESIGN: Case-control study. ANIMALS: 148 dogs that died or were
      euthanized within 48 hours after undergoing anesthesia or sedation and for which
      anesthesia could not be reasonably excluded as a contributory factor (cases) and
      487 control dogs that did not die within 48 hours after undergoing anesthesia or
      sedation (controls). PROCEDURES: Details of patient characteristics, preoperative
      evaluation and preparation, procedure, anesthetic and sedative agents used,
      monitoring, postoperative management, and personnel involved were recorded. Mixed
      effects logistic regression modeling was used to identify factors associated with
      anesthetic-related death. RESULTS: An increase in physical status grade, urgency
      of the procedure, age, or intended duration of the procedure; a decrease in body
      weight; anesthesia for a major versus a minor procedure; and use of injectable
      agents for anesthetic induction and halothane for maintenance or use of inhalant
      anesthetics alone (compared with use of injectable agents for induction and
      isoflurane for maintenance) were associated with increased odds of anesthetic
      related death. CONCLUSIONS AND CLINICAL RELEVANCE: The results suggested that
      specific factors could be associated with increased odds of anesthetic-related
      death in dogs. Knowledge of these factors should aid the preoperative assessment
      and perioperative management of dogs undergoing anesthesia and sedation.

PMID- 18828721
TI  - Association of pruritus with anxiety or aggression in dogs.
AB  - OBJECTIVE: To evaluate the association between pruritus and anxiety-related and
      aggressive behaviors in dogs. DESIGN: Cross-sectional survey. ANIMALS: 238 dogs
      between 1 and 8 years old. PROCEDURES: Information including a score for general
      degree of pruritus (visual analogue scale from 0 to 10) and frequency of anxiety
      related and aggressive behaviors was collected via a survey distributed to
      clients at 3 privately owned practices. RESULTS: Median score for pruritus was
      2.4. Dogs were assigned to 2 groups on the basis of pruritus score (nonpruritic
      [0 to 2.4] and pruritic [2.5 to 10]). There was no significant difference between
      pruritic and nonpruritic dogs with regard to aggression or with regard to
      reactivity to being alone; to thunderstorms or noises; or to unfamiliar people,
      animals, or objects. Post hoc analysis revealed significantly more reactivity to
      thunderstorms or noises in dogs treated with glucocorticoids (18/37 [49%]) than
      in those not administered glucocorticoids (57/197 [29%]). CONCLUSIONS AND
      CLINICAL RELEVANCE: An association was not detected between pruritus and
      aggressive, anxious, or fearful behavior in dogs. There was greater reactivity to
      thunderstorms or noises in glucocorticoid-treated dogs. These findings do not
      preclude the possibility of a relationship between certain dermatoses or pruritic
      conditions and behavior. However, a concurrent behavioral abnormality cannot be
      assumed to result from a dermatosis and be expected to resolve with treatment of
      only the skin disease. Dogs with behavioral disorders and pruritic disease
      require primary treatment of both conditions. Additional studies to examine the
      effect of disease and glucocorticoids on canine behavior are warranted.

PMID- 18828722
TI  - Diagnosis and treatment of blastomycosis affecting the nose and nasopharynx of a
      dog.
AB  - CASE DESCRIPTION: A 2-year-old 38.9-kg (85.58-lb) sexually intact male German
      Shepherd Dog was examined because of a 4-month history of severe nasal swelling
      and nasal mucosa congestion. The signs were slowly progressive. CLINICAL
      FINDINGS: Physical examination revealed that the dorsal aspect of the dog's nose
      was swollen and hard. Mucous membranes in both nostrils were hyperemic and
      edematous. Diagnostic investigation revealed severe nasal osteolysis and
      pyogranulomatous rhinitis and nasopharyngitis attributable to blastomycosis.
      TREATMENT AND OUTCOME: Oral administration of itraconazole was initiated (5 mg/kg
      [2.27 mg/lb], q 12 h for 5 days and then q 24 h). After a treatment period of 3
      months, the nose had regained its normal appearance. After 5 months of treatment,
      the Blastomyces infection was eliminated as confirmed by results of rhinoscopy
      and biopsy specimen examination. No relapse was evident within 1 year after
      discontinuation of treatment. CLINICAL RELEVANCE: In dogs, nasal and
      nasopharyngeal blastomycosis can result in severe osteolysis of the nasal bone.
      Resolution of disease can be achieved with oral administration of itraconazole
      for a period of at least 5 months.

PMID- 18828723
TI  - Osteolysis of the radius and ulna induced by a circumferential foreign body in a
      cat.
AB  - CASE DESCRIPTION: A 1-year-old neutered male cat was examined because of a 6
      month history of recurrent swelling and draining wounds affecting the
      craniomedial aspect of the distal portion of the left forelimb. CLINICAL
      FINDINGS: No lameness or neurologic deficits were evident. Examination of
      craniocaudal and lateromedial radiographic views revealed nonprogressive
      circumferential osteolysis and a mildly radiopaque, ring-shaped foreign body
      surrounding the radius and ulna. TREATMENT AND OUTCOME: During surgery, a tight
      elastic band surrounded by a thick fibrous tissue capsule was found encircling
      the limb. Microbial culture yielded a Staphylococcus sp that was susceptible to
      clindamycin. Follow-up monitoring via telephone communication with the owners 1.5
      years after removal of the foreign body indicated that the cat had healed with no
      recurrence of drainage. CLINICAL RELEVANCE: Pressure osteolysis of the bones of
      the forelimb can be caused by a circumferential foreign body without associated
      neurologic abnormalities or lameness.

PMID- 18828724
TI  - A survey to determine public opinion about the ethics and governance of farm
      animal welfare.
AB  - OBJECTIVE: To determine the attitude of the public toward farm animal welfare and
      identify beliefs regarding how decisions about farm animal welfare should be
      made. DESIGN: Telephone survey. STUDY POPULATION: A random sample of 1,019 US
      households. PROCEDURES: US households were contacted by telephone and asked to
      take part in a survey consisting of 48 items. RESULTS: A majority (437/773
      [56.4%]) of respondents believed decisions about farm animal welfare should be
      made by experts rather than being based on the views of the public. Such
      advocates of expert decision making were less likely to believe the government
      should regulate farm animal welfare. Most (420/773 [54.3%]) respondents believed
      decisions about farm animal welfare should be based on scientific measures of
      animal well-being, as opposed to moral and ethical considerations. Those
      individuals who believed farm animal welfare decisions should be made by experts
      and be based on scientific measures were the least concerned about farm animal
      welfare issues. People who believed animal welfare decisions should be made by
      experts and be based on scientific measures were most responsive to information
      about use of gestation crates for sows. CONCLUSIONS AND CLINICAL RELEVANCE: These
      results should help increase recognition that changing public opinion is not
      simply a matter of convincing the public to support positions established by
      veterinarians and animal scientists. People's views about the role of the
      democratic process in regulating technologic change are important determinants of
      whether people accept the changes in animal agriculture that have occurred during
      the past century.

PMID- 18828725
TI  - Clinical Parelaphostrongylus tenuis infection in two captive American bison
      (Bison bison).
AB  - CASE DESCRIPTION: 2 juvenile (17 and 19 months of age) male American bison (Bison
      bison) were examined because of acute bilateral hind limb weakness and ataxia; 1
      animal also had urinary incontinence. TREATMENT AND OUTCOME: Given the clinical
      signs and rapid deterioration in the condition of these 2 animals, obtaining a
      definitive diagnosis was considered essential to minimizing the risk of disease
      in the remaining bison herd and among other animals at the facility. Therefore,
      both affected animals were euthanized. At necropsy, no gross abnormalities were
      seen. Histologic examination of sections of the brains from both animals revealed
      mild to moderate multifocal aggregates of eosinophils and mononuclear cells in
      perivascular regions of the meninges and gray matter of the cerebrum, cerebellum,
      and brainstem. Systematic examination of multiple sections of brain and spinal
      cord revealed evidence of nematode sections and aberrant parasite migration.
      CLINICAL RELEVANCE: Findings suggested that CNS migration of Parelaphostrongylus
      tenuis in American bison may cause clinical signs. These findings have
      implications for the management of captive bison and free-ranging bison sharing
      ranges with white-tailed deer (Odocoileus virginianus), the definitive host, and
      elk (Cervus elaphus canadensis).

PMID- 18828727
TI  - Robust hepatic gene silencing for functional studies using helper-dependent
      adenoviral vectors.
AB  - RNA interference is currently envisioned as the basis of gene function and drug
      target validation studies. This novel technology has the advantage of providing a
      remarkably faster tool for gene silencing than traditional transgenic animal
      methodologies. In vivo administration of short interfering RNA (siRNA) typically
      results in reduced target gene expression for approximately 1 week. Viral vectors
      offer the possibility to express constitutive levels of short hairpin RNA (shRNA)
      so that the effects of knocking down the target gene can be studied for a few
      weeks, rather than a few days. Helper-dependent vectors have a significant
      advantage over previous generations of adenoviral vectors because of their much
      higher cloning capacity, potential for long-term transgene expression, and
      enhanced safety profiles on administration in vivo. Therefore, this advanced type
      of vector is an excellent tool to carry out in vivo studies directed at
      constitutive expression of shRNA. Here we show it is possible to obtain more than
      90% target gene knockdown in an animal model of type 2 diabetes for several
      weeks, thereby consolidating this technology as an alternative to generating
      liver-specific knockout animals.

PMID- 18828728
TI  - Cytotoxic T lymphocyte responses to transgene product, not adeno-associated viral
      capsid protein, limit transgene expression in mice.
AB  - The use of adeno-associated viral (AAV) vectors for gene replacement therapy is
      currently being explored in several clinical indications. However, reports have
      suggested that input capsid proteins from AAV-2 vector particles may result in
      the stimulation of cytotoxic T lymphocyte (CTL) responses that can result in a
      loss of transduced cells. To explore the impact of anti-AAV CTLs on AAV-mediated
      transgene expression, both immunocompetent C57BL=6 mice and B cell-deficient muMT
      mice were immunized against the AAV2 capsid protein (Cap) and were injected
      intravenously with an AAV-2 vector encoding alpha-galactosidase (alpha-Gal).
      C57BL=6 mice, which developed both CTL and neutralizing antibody responses
      against Cap, failed to show any detectable alpha-Gal expression. In contrast,
      serum alpha-Gal levels comparable to those of naive mice were observed in muMT
      mice despite the presence of robust CTL activity against Cap, indicating that
      preexisting Cap-specific CTLs did not have any effect on the magnitude and
      duration of transgene expression. The same strategy was used to assess the impact
      of CTLs against the alpha-Gal transgene product on AAV-mediated gene delivery and
      persistence of transgene expression. Preimmunization of muMT mice with an
      Ad=alpha-Gal vector induced a robust CTL response to alpha-Gal. When these mice
      were injected with AAV2=alpha-Gal vector, initial levels of alpha-Gal expression
      were reduced by more than 1 log and became undetectable by 2 weeks postinjection.
      Overall, our results indicate that CTLs against the transgene product as opposed
      to AAV capsid protein are more likely to interfere with AAV transgene expression.

PMID- 18828730
TI  - Males do not reduce the fitness of their female co-twins in contemporary samples.
AB  - Lummaa et al. (2007) presented historical data collected from twins born in
      Finland between 1734 and 1888 which suggested that females (N = 31) born as part
      of an opposite sex (OS) twin pair were 25% less likely to reproduce than female
      twins (N = 35) born as part of a same sex (SS) pair. They hypothesized that this
      reduction in fitness was due to masculinization of the female fetus via prenatal
      effects of the hormones of a male fetus. Because such masculinization would
      presumably take place in modern populations as well, it would seem important to
      establish to what degree it does so, and if so, whether reproduction is affected.
      We therefore address the question of reproduction differences in individual
      female twins from same-sex (N = 1979) and opposite-sex (N = 913) dizygotic pairs
      in studies carried out in Australia, the Netherlands, and the United States. In
      all three samples, there were no differences in the number of children or age of
      first pregnancies in women from same sex pairs compared to those from opposite
      sex pairs. Similarly, there were no differences in psychological femininity
      between women from pairs of the same or opposite sex.

PMID- 18828731
TI  - Vitamin D receptor gene polymorphisms have negligible effect on human height.
AB  - Human height is a highly heritable trait, with genetic factors explaining up to
      90% of phenotypic variation. Vitamin D levels are known to influence several
      physiological processes, including skeletal growth. The vitamin D receptor (VDR)
      gene has been reported as contributing to variation in height. A meta-analysis of
      13607 adult individuals found a small but significant association with the
      rs1544410 (BsmI) polymorphism. In contrast, the meta-analysis found no effect in
      a sample of 550 children. Two recent studies reported variants with large effect
      on height elsewhere in VDR (rs10735810 [FokI] and rs7139166 [-1,521]
      polymorphisms). We genotyped large Caucasian samples from Australia (N = 3,906)
      and the Netherlands (N = 1,689) for polymorphisms in VDR. The Australian samples
      were twin families with height measures from 3 time points throughout
      adolescence. The Dutch samples were adult twins. We use the available family data
      to perform both within and between family tests of association. We found no
      significant associations for any of the genotyped variants after multiple testing
      correction. The (non-significant) effect of rs1544410 in the Australian
      adolescent cohort was in the same direction and of similar magnitude (additive
      effect 0.3 cm) to the effect observed in the published adult meta-analysis. An
      effect of this size explains approximately 0.1% of the phenotypic variance in
      height - this implies that many, probably hundreds, of such variants are
      responsible for the observed genetic variation. Our results did not support any
      role for two other regions (rs10735810, rs7139166) of VDR in explaining variation
      in height.

PMID- 18828732
TI  - Genetic and environmental influences on adiponectin, leptin, and BMI among
      adolescents in Taiwan: a multivariate twin/sibling analysis.
AB  - Circulating levels of leptin and adiponectin are closely associated with obesity.
      However, it is not known whether there are common shared genes or environment
      exerting influences on the levels of leptin, adiponectin, and BMI. We aimed to
      assess the relative contribution of genes and environment to adiponectin, leptin,
      and BMI individually as well as simultaneously to the three measures. Our
      subjects included a total of 228 twin/sibling pairs aged 12 to 18 (130
      monozygotic twins, 68 dizygotic twins and 30 sibling pairs) were recruited from
      the middle schools. Multivariate analyses were applied to twin/sibling data using
      structural equation modeling. The results showed that intraclass correlations for
      adiponectin, leptin and BMI were higher in the MZ twins than those in the DZ/SP
      group. The relative contribution of genes to adiponectin (39%) was comparable to
      those of shared environment (40%). In contrast, leptin and BMI were influenced
      mostly by genes (74% and 89%, respectively). The multivariate genetic analyses
      showed that a latent factor underlying the three measures was identified, with
      BMI being equivalent to this latent factor. The BMI-dependent genetic factor
      explains only 15% and 34% of variation of adiponectin and leptin, respectively.
      These data indicate a differential contribution of genetic factors for the
      variation of adiponectin, leptin and BMI. More importantly, only a small portion
      of the genetic influences on adiponectin and leptin was attributed to BMI. Our
      findings provided more insight into the complex regulation of adiponectin and
      leptin in obesity.

PMID- 18828733
TI  - Anthropometry, carbohydrate and lipid metabolism in the East Flanders Prospective
      Twin Survey: linkage of candidate genes using two sib-pair based variance
      components analyses.
AB  - Insulin resistance and obesity are underlying causes of type 2 diabetes and
      therefore much interest is focused on the potential genes involved. A series of
      anthropometric and metabolic characteristic were measured in 240 MZ and 112 DZ
      twin pairs recruited from the East Flanders Prospective Twin Survey.
      Microsatellite markers located close to ABCC8, ADIPOQ, GCK, IGF1, IGFBP1, INSR,
      LEP, LEPR, PPARgamma and the RETN gene were genotyped. Univariate single point
      variance components linkage analyses were performed using two methods: (1) the
      standard method, only comprising the phenotypic and genotypic data of the DZ twin
      pairs and (2) the extended method, also incorporating the phenotypic data of the
      MZ twin pairs. Suggestive linkages (LOD > 1) were observed between the ABCC8
      marker and waist-to-hip ratio and HDL-cholesterol levels. Both markers flanking
      ADIPOQ showed suggestive linkage with triglycerides levels, the upstream marker
      also with body mass and HDL-cholesterol levels. The IGFBP1 marker showed
      suggestive linkage with fat mass, fasting insulin and leptin levels and the LEP
      marker showed suggestive linkage with birth weight. This study suggests that DNA
      variants in ABCC8, ADIPOQ, IGFBP1 and LEP gene region may predispose to type 2
      diabetes. In addition, the two methods used to perform linkage analyses yielded
      similar results. This was however not the case for birth weight where
      chorionicity seems to be an important confounder.

PMID- 18828734
TI  - Adhesion molecule polymorphisms and pulse wave velocity in American youth.
AB  - BACKGROUND: Our research group recently reported that aorto-radial (radial) and
      aorto-dorsalis-pedis (foot) pulse wave velocity (PWV) as proxies of arterial
      stiffness are substantially heritable in healthy youth. This article aimed at
      uncovering the genetic contributions of adhesion molecules, key members in the
      inflammatory process, to PWV in these young individuals. METHODS: Radial and foot
      PWV were noninvasively measured with applanation tonometry in 702 black and white
      subjects (42% blacks, mean age 17.7 +/- 3.3 years) from the Georgia Cardio
      vascular Twin Study. Eight functional polymorphisms from genes for E-selectin
      (SELE), P-selectin (SELP), intercellular adhesion molecules-1 (ICAM1), and
      vascular cell adhesion molecules-1 (VCAM1) were genotyped. RESULTS: Youth with
      Ser290Asn or Asn290Asn genotype (SELP) compared to those with Ser290Ser had an
      increase in both radial and foot PWV (6.61 +/- 0.07 vs. 6.41 +/- 0.05 m/s, p =
      .026; 7.22 +/- 0.05 vs. 7.04 +/- 0.04 m/s, p = .007). TT homozygotes of rs2244529
      (SELP) had higher foot PWV (7.28 +/- 0.07 vs. 7.06 +/- 0.03 m/s, p = .002) than
      CT heterozygotes and CC homozygotes. There appeared to be a decrease in foot PWV
      in youth with the 241Arg allele (ICAM1) as compared to those without (6.96 +/-
      0.08 vs. 7.14 +/- 0.03 m/s, p = .005). For the Asp693Asp (C to T) polymorphism
      (VCAM1), CC genotype had higher foot PWV than CT and TT genotypes (7.18 +/- 0.04
      vs. 6.95 +/- 0.06 m/s, p < .0001). There was an epistatic interaction between
      Ser290Asn, Gly241Arg, and Asp693Asp on foot PWV (p = .017), explaining 3.6%
      variance of the foot PWV. CONCLUSION: Genetic variation of adhesion molecules may
      be implicated in the development of arterial stiffness. Screening for adhesion
      molecule polymorphisms may help identify high-risk youth.

PMID- 18828735
TI  - Phenotypic and genetic associations between the big five and trait emotional
      intelligence.
AB  - This study reports the first behavioral genetic investigation of the extent to
      which genetic and/or environmental factors contribute to the relationship between
      the Big Five personality factors and trait emotional intelligence. 213 pairs of
      adult monozygotic twins and 103 pairs of same-sex dizygotic twins completed the
      NEO-PI-R and the Trait Emotional Intelligence Questionnaire (TEIQue). Replicating
      previous non-twin studies, many significant phenotypic correlations were found
      between the Big Five factors - especially Neuroticism, Extraversion, and
      Conscientiousness - and the facets, factors, and global scores derived from the
      TEIQue. Bivariate behavioral genetic model-fitting analyses revealed that these
      phenotypic correlations were primarily attributable to correlated genetic factors
      and secondarily to correlated non-shared environmental factors. The results
      support the feasibility of incorporating EI as a trait within existing
      personality taxonomies.

PMID- 18828736
TI  - Phenotypic, genetic, and environmental properties of the portrait values
      questionnaire.
AB  - The purpose of the present study was to examine the 10 value types from the
      Portrait Values Questionnaire (PVQ; Schwartz et al., 2001) both at the phenotypic
      (observed) level as well as the genetic and environmental level. Australian twins
      (N = 695) completed the PVQ as part of a larger questionnaire battery. Nine of
      the value types were found to have a genetic component with heritability
      estimates ranging from 10.8% for power to 38% for conformity. The achievement
      scale was best explained by environmental factors. The interscale correlations
      were found to range from -.02 to .70 at the phenotypic level. Of these 45
      correlations, 16 were found to be explained by overlapping genetic factors and
      almost all (41) were found to have significant unique environment correlations.

PMID- 18828737
TI  - Sleep during a regular week night: a twin-sibling study.
AB  - Previous genetic investigations of variation in normal sleep have focused on
      measures that describe sleep over longer periods of time. We undertook a study
      with the aim of evaluating whether heritability can be found in single-night
      sleep traits. A classical twin study design of monozygotic and dizygotic twins,
      enriched with siblings of twins was employed. The study included adult twin pairs
      and their siblings (N = 813 subjects from 342 families). A subsample of 66
      individuals participated twice. For a single night, bedtime, awakening time and
      subjective sleep quality were assessed using a diary. The diary also assessed
      smoking, alcohol and coffee consumption, and the subjective evaluation of stress.
      Resemblance between family members was used to estimate the heritability of
      bedtime, awakening time, sleep problems and sleep quality as a function of sex.
      Most sleep measures showed familial clustering, but results differed for men and
      women. Heritability for bedtime and sleep problems was seen in women; and for
      awakening time in men. We conclude that heritability can be demonstrated for
      bedtime and subjective evaluation of even a single night of sleep. The
      contribution of the genetic make-up is sex specific. In women variance in
      awakening time is so affected by environmental circumstances, that the genetic
      contribution to the variance becomes negligible. In contrast, for males, variance
      in the evening bedtime is so affected by environmental circumstances, that the
      genetic contribution to the variance becomes negligible.

PMID- 18828738
TI  - An application of salivary DNA in twin research of Chinese children.
AB  - Since saliva collection is noninvasive, painless and inexpensive, it may become
      an alternative to obtain genomic DNA, which is critical to evaluate zygosity and
      the role of genetic factors in twin research. This study provided a rough
      description of salivary DNA in Chinese twin children, and presented the DNA yield
      and quality extracted from saliva in a large-scale children sample, which
      supplied an example for saliva sample using in genetic epidemiology. Three
      milliliters of saliva was collected from 356 twin children aged 6 to 15, and DNA
      was extracted by a commercial DNA isolation kit. The DNA yield and purity was
      determined by spectrophotometry at 260 nm and 280 nm. The zygosity determination
      of the same-sex twins and the assay of Polymerase Chain Reaction-Restriction
      Fragment Length Polymorphism indicated the quality of salivary DNA. The amount of
      extracted DNA from three milliliters of saliva was about 34.91 microg (2.20
      approximately 122.04 microg), average OD(260/280) values was 1.84. Saliva DNA is
      a reliable sample for the determination of twins' zygosity. We conclude that
      saliva may be a feasible and reliable source of DNA for genetic epidemiology
      studies, especially for twin research.

PMID- 18828739
TI  - Prediction of spontaneous preterm delivery in twin pregnancies by cervical length
      at mid-gestation.
AB  - The objective of our study was to evaluate the correlation of the cervical length
      at 20-25 weeks of gestation with the incidence of spontaneous preterm delivery in
      twins in a country with a high incidence of preterm delivery compared to other
      European countries. Cervical length was measured in 262 consecutive patients.
      Previous preterm delivery before 34 weeks of gestation, chorionicity, maternal
      age, body-mass-index, smoking habit and parity were recorded as risk factors for
      preterm delivery. Women who were symptomatic at 20-25 weeks and who delivered
      because of other reasons than spontaneous labour and preterm rupture of membranes
      or at term were excluded. The primary outcome was incidence of preterm birth
      before 34 weeks. Two hundred and twenty-three patients were analyzed. Thirty-two
      (14%) delivered before 34 weeks. There was a significant correlation between
      cervical length of less than 25 mm and spontaneous delivery before 34 weeks (50%
      vs. 13%, p = .007). In addition, logistic regression analysis found cervical
      length to be the only significant predictor of spontaneous delivery before 34
      weeks (OR 1.084; 95% CI 1.015; 1.159; p = .017). We conclude that the risk of
      severe preterm delivery in twins is high. Cervical length at mid-gestation was
      the only predictor of delivery before 34 weeks.

PMID- 18828740
TI  - Maternal age and temporal effects on stillbirth rates.
AB  - Stillbirth rates among single and multiple births show markedly decreasing
      temporal trends. In addition, several studies have demonstrated that the
      stillbirth rates are dependent on maternal age, in general, showing a U- or J
      shaped association with maternal age. In this study, the temporal trends in and
      the effect of maternal age on the stillbirth rate were considered simultaneously.
      Our goal was to split the variation into temporal trends and maternal age
      effects. We applied two-dimensional analysis of variance because no linear
      association between maternal age and stillbirth rate can be assumed. The temporal
      trends of stillbirth rates also were not clearly linear. However, the possibility
      of applying regression analyses based on linear time trends was also considered.
      Our study is mainly based on official data from England and Wales for the period
      between 1927 and 2004. These results were compared with registered birth data
      from Finland between 1937 and 1997. The best fit was obtained when the models
      were built for the logarithm of the stillbirth rate. Our interpretation of this
      result is that an association exists between the effects of the factors and the
      mean stillbirth rate, and consequently, a multiplicative model was applied.
      Relatively high stillbirth rates were observed among twin births of young mothers
      and among all births of older mothers.

PMID- 18828741
TI  - Dramatically different dizygotic twins: will we include them in Research? Twin
      research reviews: congenital anomalies, mirror-image effects in conjoined twins,
      older mothers of twins; Twin statistics: 'Massachusetts, land of twins'; Tribute:
      Dr Victor A. McKusick.
AB  - The increased frequency of interracial marriage is a likely source of unusual
      looking dizygotic (DZ) twins. Some members of DZ twin pairs born to mixed-race
      couples inherit very different physical features from their parents. This raises
      several questions, such as: Will researchers wish to include such twins in their
      ongoing studies? Next, new twin research concerned with congenital anomalies,
      mirror-image effects in conjoined twins and older mothers of twins will be
      reviewed. New statistics on twinning rates in Massachusetts will also be
      summarized, followed by a tribute to the late medical geneticist Dr. Victor A.
      McKusick.

PMID- 18828742
TI  - Respiratory syncytial virus persistence in the lungs correlates with airway
      hyperreactivity in the mouse model.
AB  - BACKGROUND: Previous studies in mice showed that respiratory syncytial virus
      (RSV) infection was associated with RSV RNA persistence. This study was designed
      to characterize the significance of RSV RNA persistence and its relation to RSV
      induced chronic airway disease. METHODS: Mice were inoculated with live RSV, UV
      light-treated RSV, heat-inactivated RSV, or medium. Bronchoalveolar lavage fluid
      samples were obtained and lung specimens were harvested on days 1, 5, and 42
      after inoculation to assess lung inflammation, lung mRNA expression of
      interleukin (IL)-4, IL-5, IL-15, and interferon (IFN)-gamma; RSV loads were
      assessed by culture and real-time polymerase chain reaction (PCR) and correlated
      with pulmonary function. RESULTS: During the acute phase of infection, RSV loads
      as indicated by culture and PCR were significantly higher in mice inoculated with
      live RSV. On day 42, RSV RNA remained detectable only in mice inoculated with
      live or UV light-treated RSV. Lung inflammation, IFN-gamma:IL-4 mRNA expression
      ratios, airway obstruction (AO), and airway hyperreactivity (AHR) were
      significantly increased in mice inoculated with live RSV. AO on day 5 and AHR on
      day 42 were significantly correlated with RSV RNA copy number in lung samples.
      CONCLUSIONS: Infection with live RSV induced acute and chronic airway disease
      that was associated with a predominantly Th-1 immune response and RSV RNA
      persistence that significantly correlated with pulmonary function abnormalities.

PMID- 18828743
TI  - Evaluation of the immune response to a 2-dose measles vaccination schedule
      administered at 6 and 9 months of age to HIV-infected and HIV-uninfected children
      in Malawi.
AB  - BACKGROUND: The World Health Organization recommends that infants at high risk
      for developing measles before 9 months of age, including human immunodeficiency
      virus (HIV)-infected infants, receive measles vaccination (MV) at 6 and 9 months
      of age. METHODS: Children born to HIV-infected mothers received MV at 6 and 9
      months, and children of HIV-uninfected mothers were randomized to receive MV at 6
      and 9 months, MV at 9 months, or routine MV without follow-up. Blood samples were
      obtained before and 3 months after each MV. Data were collected on adverse events
      for 21 days after each MV, at all clinic visits, on any hospitalization, and for
      subjects who died. HIV-infection status was determined by antibody assays and
      polymerase chain reaction; the presence of measles IgG was determined by EIA.
      RESULTS: Twenty-two hundred mother-infant pairs were enrolled. After the first
      and second doses of measles vaccine, respectively, the percentages of children
      who were measles seropositive were 59% (36 of 61) and 64% (29 of 45) among HIV
      infected children, 68% (152 of 223) and 94% (189 of 202) among HIV-exposed but
      uninfected children, and 62% (288 of 467) and 92% (385 of 417) among HIV
      unexposed children. Of 521 HIV-unexposed children vaccinated only at 9 months,
      398 (76%) were measles seropositive at 12 months. No serious vaccine-related
      adverse events were identified. CONCLUSIONS: An early, 2-dose MV schedule was
      immunogenic, but a higher proportion of HIV-infected children remained
      susceptible to measles, compared with HIV-uninfected children (whether HIV
      exposed or HIV unexposed).

PMID- 18828744
TI  - The structure of clines with fitness-dependent dispersal.
AB  - Spatial models commonly assume that dispersal does not depend on environmental
      conditions or phenotype. For example, these assumptions underpin explanations for
      clines on the basis of a trade-off between dispersal and local adaptation. We
      reexamine clines when an individual's decisions over whether and where to
      disperse depend on its fitness. We compare fitness-dependent dispersal with cases
      where dispersal responds to juvenile survivorship only. Clines are steeper the
      more responsive dispersal is to environmental conditions for all dispersal
      behaviors that we consider. Clines eventually become stepped as the
      responsiveness of dispersal to environmental conditions is increased for half of
      the dispersal behaviors we consider, but smooth clines are maintained for the
      remaining cases. Smooth clines are maintained by the biased movement of
      individuals out of the hybrid zone when individuals move directionally in
      response to gradients in juvenile survivorship, which is a different mechanism to
      that maintaining smooth clines in classic cline theory.

PMID- 18828745
TI  - The timescale of phenotypic plasticity and its impact on competition in
      fluctuating environments.
AB  - Although phenotypic plasticity can be advantageous in fluctuating environments,
      it may come too late if the environment changes fast. Complementary chromatic
      adaptation is a colorful form of phenotypic plasticity, where cyanobacteria tune
      their pigmentation to the prevailing light spectrum. Here, we study the timescale
      of chromatic adaptation and its impact on competition among phytoplankton species
      exposed to fluctuating light colors. We parameterized a resource competition
      model using monoculture experiments with green and red picocyanobacteria and the
      cyanobacterium Pseudanabaena, which can change its color within approximately 7
      days by chromatic adaptation. The model predictions were tested in competition
      experiments, where the incident light color switched between red and green at
      different frequencies (slow, intermediate, and fast). Pseudanabaena (the flexible
      phenotype) competitively excluded the green and red picocyanobacteria in all
      competition experiments. Strikingly, the rate of competitive exclusion was much
      faster when the flexible phenotype had sufficient time to fully adjust its
      pigmentation. Thus, the flexible phenotype benefited from its phenotypic
      plasticity if fluctuations in light color were relatively slow, corresponding to
      slow mixing processes or infrequent storms in their natural habitat. This shows
      that the timescale of phenotypic plasticity plays a key role during species
      interactions in fluctuating environments.

PMID- 18828746
TI  - Sex-based cardiac physiology.
AB  - Biological sex plays an important role in normal cardiac physiology as well as in
      the heart's response to cardiac disease. Women generally have better cardiac
      function and survival than do men in the face of cardiac disease; however, this
      sex difference is lost when comparing postmenopausal women with age-matched men.
      Animal models of cardiac disease mirror what is seen in humans. Sex steroid
      hormones contribute significantly to sex-based differences in cardiac disease
      outcomes. Estrogen is generally considered to be cardioprotective, whereas
      testosterone is thought to be detrimental to heart function. Environmental
      estrogen-like molecules, such as phytoestrogens, can also affect cardiac
      physiology in both a positive and a negative manner.

PMID- 18828760
TI  - NFAT directly regulates Nkx2-5 transcription during cardiac cell differentiation.
AB  - BACKGROUND INFORMATION: The transcription factor NFAT (nuclear factor of
      activated T-cell) family comprises important regulators in immuno-responses and
      mouse embryonic development, including early cardiovascular and heart valve
      development. The mechanism involved, however, is not fully understood. Nkx2-5
      (NK2 transcription factor related, locus 5) is one of the earliest genes
      expressed in early cardiac progenitor cells and is essential for heart tube
      development by control of a subset of cardiac muscle-specific genes. Previously
      we found that downregulation of mitochondrial respiratory chain complex I caused
      severe cardiac deficiencies during heart tube development in Xenopus embryos
      associated with compromised Nkx2-5 expression. However, the heart defects and
      Nkx2-5 expression could be rescued by a constitutively activated NFAT, suggesting
      a possible link between NFAT and Nkx2-5 during early heart development. RESULTS:
      In the present study, we demonstrate that NFAT regulates Nkx2-5 expression in
      both mouse ES (embryonic stem) cells and P19 cells, a mouse model for embryonic
      differentiation. We found that there are six core NFAT-binding elements in the 5'
      regulatory region of the Nkx2-5 gene. Although NFAT is able to bind directly to
      all but one of these elements, it activates Nkx2-5 transcription only via a
      specific binding site in the distal enhancer region. Interestingly, the
      transcriptional activity of NFAT is largely dependent on the co-factor GATA (GATA
      binding transcription factor), which binds to an element adjacent to this key
      NFAT-binding site. Furthermore, binding of the endogenous NFAT to this particular
      site was observed during cardiac differentiation in mouse ES and P19 cells.
      CONCLUSIONS: The results suggest that Nkx2-5 is a direct target of NFAT that co
      ordinates with other transcription factors such as GATA4 to regulate Nkx2-5
      during cardiogenesis.

PMID- 18828761
TI  - Oleoyl-oestrone inhibits lipogenic, but maintains thermogenic, gene expression of
      brown adipose tissue in overweight rats.
AB  - In the present study we intended to determine how BAT (brown adipose tissue)
      maintained thermogenesis under treatment with OE (oleoyl-oestrone), a powerful
      slimming hormone that sheds off body lipid but maintains the metabolic rate.
      Overweight male rats were subjected to daily gavages of 10 nmol/g of OE or
      vehicle (control) for 10 days. A PF (pair-fed) vehicle-receiving group was used
      to discount the effects attributable to energy availability limitation.
      Interscapular BAT mass, lipid, DNA, mRNA and the RT-PCR (real-time PCR)
      expression of lipid and energy metabolism genes for enzymes and regulatory
      proteins were measured. BAT mass and lipid were decreased in OE and PF, with the
      latter showing a marked reduction in tissue mRNA. Maintenance of perilipin gene
      expression in PF and OE rats despite the loss of lipid suggests the preservation
      of the vacuolar interactive surface, a critical factor for thermogenic
      responsiveness. OE and, to a lesser extent, PF maintained the expression of genes
      controlling lipolysis and fatty acid oxidation, but markedly decreased the
      expression of those genes involved in lipogenic and acyl-glycerol synthesis. OE
      did not affect UCP1 (uncoupling protein 1) (decreased in PF), beta(3) adrenergic
      receptors or hormone-sensitive lipase gene mRNAs, which may translate in
      maintaining a full thermogenic system potential. OE rats were able to maintain a
      less energetically stressed BAT (probably through glucose utilization) than PF
      rats. These changes were not paralleled in PF rats, in which lower thermogenesis
      and glucose preservation resulted in a heavier toll on internal fat stores. Thus
      the mechanism of action of OE is more complex and tissue-specific than previously
      assumed.

PMID- 18828762
TI  - Is the transplant drug glass half empty or half full?

PMID- 18828763
TI  - Debating the ethics of transplanting bad guys.

PMID- 18828764
TI  - What's next in the pipeline.
AB  - The first decade of the new millennium has been disappointing for transplant
      therapeutics: no new immunosuppression agents have been approved. Several high
      profile drugs and biologics failed the rigors of clinical trials or had
      disappointing preclinical results (FTY720, FK778, anti-CDI54, anti-IL15, anti
      CD28, R3421). Several challenges face the industry and clinical investigators in
      bringing novel drugs to the clinic including the difficulty in targeting new
      endpoints for toxicities or chronic allograft disease since acute rejection has
      been reduced to below 15% as well as the Food and Drug Administration insistence
      of excluding the use of immunosuppression regimens embraced by the transplant
      community in control arms of clinical trials. Currently six new agents, 3 small
      molecules (ISA247, a semisynthetic analogue of cyclosporine; AEB071, a protein
      kinase C isoforms inhibitor; CP 690,550, a selective Janus kinase inhibitor) are
      in phase II trials and 3 biologics (belatacept, a second generation CTLA4Ig;
      efalizumab, a humanized antiCD11a [LFA1] monoclonal antibody; and alefacept, a
      LFA3-IgG1 fusion receptor protein) are in phase II/III clinical trials. The
      preclinical pipeline is not only full but promises to address previously
      neglected targets and fulfill unmet medical needs in transplant therapeutics.

PMID- 18828765
TI  - The clinical impact of islet transplantation.
AB  - Islet cell transplantation has recently emerged as one of the most promising
      therapeutic approaches to improving glycometabolic control in diabetic patients
      and, in many cases, achieving insulin independence. Unfortunately, many
      persistent flaws still prevent islet transplantation from becoming the gold
      standard treatment for type 1 diabetic patients. We review the state of the art
      of islet transplantation, outcomes, immunosuppression and--most important--the
      impact on patients' survival and long-term diabetic complications and eventual
      alternative options. Finally, we review the many problems in the field and the
      challenges to islet survival after transplantation. The rate of insulin
      independence 1 year after islet cell transplantation has significantly improved
      in recent years (60% at 1 year posttransplantation compared with 15% previously).
      Recent data indicate that restoration of insulin secretion after islet cell
      transplantation is associated with an improvement in quality of life, with a
      reduction in hypoglycemic episodes and potentially with a reduction in long-term
      diabetic complications. Once clinical islet transplantation has been successfully
      established, this treatment could even be offered to diabetic patients long
      before the onset of diabetic complications.

PMID- 18828766
TI  - Murine mobilized peripheral blood stem cells have a lower capacity than bone
      marrow to induce mixed chimerism and tolerance.
AB  - Allogeneic bone marrow transplantation (BMT) under costimulation blockade allows
      induction of mixed chimerism and tolerance without global T-cell depletion (TCD).
      The mildest such protocols without recipient cytoreduction, however, require
      clinically impracticable bone marrow (BM) doses. The successful use of mobilized
      peripheral blood stem cells (PBSC) instead of BM in such regimens would provide a
      substantial advance, allowing transplantation of higher doses of hematopoietic
      donor cells. We thus transplanted fully allogeneic murine granulocyte colony
      stimulating factor (G-CSF) mobilized PBSC under costimulation blockade (anti
      CD40L and CTLA4Ig). Unexpectedly, PBSC did not engraft, even when very high cell
      doses together with nonmyeloablative total body irradiation (TBI) were used. We
      show that, paradoxically, T cells contained in the donor PBSC triggered rejection
      of the transplanted donor cells. Rejection of donor BM was also triggered by the
      cotransplantation of unmanipulated donor T cells isolated from naive
      (nonmobilized) donors. Donor-specific transfusion and transient immunosuppression
      prevented PBSC-triggered rejection and mixed chimerism and tolerance were
      achieved, but graft-versus-host disease (GVHD) occurred. The combination of in
      vivo TCD with costimulation blockade prevented rejection and GVHD. Thus, if
      allogeneic PBSC are transplanted instead of BM, costimulation blockade alone does
      not induce chimerism and tolerance without unacceptable GVHD-toxicity, and the
      addition of TCD is required for success.

PMID- 18828767
TI  - Transplant acceptance following anti-CD4 versus anti-CD40L therapy: evidence for
      differential maintenance of graft-reactive T cells.
AB  - Inductive therapy with anti-CD4 or anti-CD40L monoclonal antibodies (mAb) leads
      to long-term allograft acceptance but the immune parameters responsible for graft
      maintenance are not well understood. This study employed an adoptive transfer
      system in which cells from mice bearing long-term cardiac allografts following
      inductive anti-CD4 or anti-CD40L therapy were transferred into severe combined
      immunodeficiency (SCID) allograft recipients. SCID recipients of cells from anti
      CD4-treated mice (anti-CD4 cells) did not reject allografts while those receiving
      cells from anti-CD40L-treated mice (anti-CD40L cells) did reject allografts.
      Carboxyfluorescein succinimidyl ester (CFSE) labeling of transferred cells
      revealed that this difference was not associated with differential proliferative
      capacities of these cells in SCID recipients. Like cells from naive mice, anti
      CD40L cells mounted a Th1 response following transfer while anti-CD4 cells
      mounted a dominant Th2 response. Early (day 10) T-cell priming was detectable in
      both groups of primary allograft recipients but persisted to day 30 only in
      recipients treated with anti-CD4 mAb. Thus, anti-CD40L therapy appears to result
      in graft-reactive T cells with a naive phenotype while anti-CD4 therapy allows
      progression to an altered state of differentiation. Additional data herein
      support the notion that anti-CD40L mAb targets activated, but not memory, cells
      for removal or functional silencing.

PMID- 18828768
TI  - Donor Fas is not necessary for T-cell-mediated rejection of mouse kidney
      allografts.
AB  - It is important to resolve whether T-cell-mediated rejection (TCMR) is mediated
      by contact-dependent cytotoxicity or by contact-independent inflammatory
      mechanisms. We recently showed that the cytotoxic molecules perforin and
      granzymes A and B are not required for TCMR of mouse kidney transplants.
      Nevertheless, TCMR could still be mediated by cytotoxicity via Fas on donor cells
      engaging Fas ligand on host T cells. We examined whether the diagnostic TCMR
      lesions would be abrogated if donor Fas was absent, particularly in hosts
      deficient in perforin or granzymes A and B. Kidneys from Fas-deficient donors
      transplanted into major histocompatibility complex (MHC)- mismatched hosts
      developed tubulitis and diffuse interstitial infiltration indistinguishable from
      wild-type (WT) allografts, even in hosts deficient in perforin and granzymes A
      and B. Gene expression analysis revealed similar molecular disturbances in Fas
      deficient and WT allografts at day 21 transplanted into WT, perforin and granzyme
      A/B-deficient hosts, indicating epithelial injury and dedifferentiation. Thus,
      donor Fas is not necessary for TCMR diagnostic lesions or molecular changes, even
      in the absence of perforin-granzyme mechanisms. We propose that in TCMR,
      interstitial effector T cells mediate parenchymal injury by inflammatory
      mechanisms that require neither the perforin-granzyme nor the Fas-Fas ligand
      cytotoxic mechanisms.

PMID- 18828770
TI  - Anesthesia-related complications in living liver donors: the experience from one
      center and the reporting of one death.
AB  - Living donor liver transplantation has become an alternative therapy for patients
      with end-stage liver disease. Donors are healthy individuals and donor safety is
      the primary concern. The objective of this study was to evaluate the anesthetic
      complications and outcomes for our donor cases; we report one death. The charts
      of the patients who underwent donor hepatectomy from February 1997 to June 2007
      were retrospectively reviewed. Right hepatectomy (resection of segments 5-8) was
      done in 101 donors, left lobectomy (resection of segments 2-3) in 11 donors, and
      left hepatectomy (resection of segments 2-4) in one donor. Minor anesthetic
      complications were shoulder pain, pruritus and urinary retention related to
      epidural morphine, and major morbidity included central venous catheter-induced
      thrombosis of the brachial and subclavian vein, neuropraxia, foot drop and
      prolonged postdural puncture headache. One of 113 donors died from pulmonary
      embolism on the 11th postoperative day. This procedure has some major risks
      related to anesthesia and surgery. Although careful attention will lower
      complication rate, we have to keep in mind that the risks of donor surgery will
      not be completely eliminated.

PMID- 18828771
TI  - Prevention of posttransplant cytomegalovirus disease and related outcomes with
      valganciclovir: a systematic review.
AB  - The precise impact of valganciclovir as preventive therapy for cytomegalovirus
      (CMV) in solid organ transplant (SOT) recipients is not fully defined. Data from
      studies using valganciclovir as preemptive therapy or prophylaxis for CMV in SOT
      recipients were synthesized for descriptive analysis. CMV disease occurred in
      2.6% and 9.9% of the patients receiving valganciclovir as preemptive therapy and
      prophylaxis, respectively. Although the incidence of early-onset (<or=90 days
      posttransplant) CMV disease was only 0.8% and 1.2% in all patients and R-/D+
      patients receiving valganciclovir prophylaxis, the incidence of late-onset (>90
      days posttransplant) CMV disease rose up to 8.9% and 17.7% in the prophylactic
      group, respectively. On the contrary, no patients developed late-onset CMV
      disease in preemptive group. Both approaches with valganciclovir have
      successfully decreased CMV disease in SOT recipients. Late-onset CMV disease is a
      complication observed uniquely with valganciclovir prophylaxis, particularly in R
      /D+ patients, but not with preemptive therapy.

PMID- 18828769
TI  - The effect of costimulatory and interleukin 2 receptor blockade on regulatory T
      cells in renal transplantation.
AB  - Regulatory T cells (Treg) are critical regulators of immune tolerance. Both IL-2
      and CD28-CD80/CD86 signaling are critical for CD4(+)CD25(+)FOXP3(+) Treg survival
      in mice. Yet, both belatacept (a second-generation CTLA-4Ig) and basiliximab (an
      anti-CD25 monoclonal antibody) are among the arsenal of current immunotherapies
      being used in kidney transplant patients. In this study, we explored the direct
      effect of basiliximab and belatacept on the Tregs in peripheral blood both in the
      short term and long term and in kidney biopsies of patients with acute rejection.
      We report that the combined belatacept/basiliximab therapy has no long-term
      effect on circulating Tregs when compared to a calcineurin inhibitor (CNI)
      treated group. Moreover, belatacept-treated patients had a significantly greater
      number of FOXP3(+) T cells in graft biopsies during acute rejection as compared
      to CNI-treated patients. Finally, it appears that the basiliximab caused a
      transient loss of both FOXP3(+) and FOXP3(-) CD25(+) T cells in the circulation
      in both treatment groups raising important questions about the use of this
      therapy in tolerance promoting therapeutic protocols.

PMID- 18828772
TI  - Alemtuzumab induction and steroid-free maintenance immunosuppression in pancreas
      transplantation.
AB  - Alemtuzumab is a humanized anti-CD52 antibody that depletes lymphocytes and has
      been increasingly used as induction agent in transplantation. The impact of
      alemtuzumab induction immunosuppression in pancreas transplantation was
      evaluated, with particular reference to steroid avoidance in maintenance. A total
      of 100 patients who received 102 pancreas transplants (83 simultaneous kidney
      pancreas [SPK], 15 pancreas after kidney transplantation [PAK] and 4 pancreas
      transplant alone [PTA]) were included. All patients received two doses of 30-mg
      alemtuzumab i.v. with tacrolimus (trough level 8-12 ng/mL) and mycophenolate
      mofetil (MMF,1g/day) with no maintenance steroids. This analysis included 62 male
      and 38 female recipients, with mean (+/-SD) age of 42 (+/-7.6) years. Median
      follow-up was 17 months (range 8-41 months). One-year patient, pancreas and
      kidney graft survival (actuarial) was 97%, 89% and 94%, respectively. Overall
      incidence of rejection was 25%. Side effects of alemtuzumab administration
      included thrombocytopenia (14%), pulmonary edema (2%) and rash (1%). Twenty-five
      percent required reoperations (12% for bleeding). Infectious complications
      included Cytomegalovirus (CMV,6.8%) BK viruria (3.8%), fungal infections (4%),
      primary varicella (1%) and posttransplant lymphoproliferative disorders
      (PTLD,1%). Eighty-three percent did not require any steroids posttransplant.
      These results indicate that alemtuzumab is safe and enables pancreas
      transplantation to be carried out without maintenance steroids in 83% of cases
      and acceptable rejection rate.

PMID- 18828773
TI  - Female-versus-male alloreactivity as a model for minor histocompatibility
      antigens in hematopoietic stem cell transplantation.
AB  - H-Y encoded gene products were the first to be recognized as clinically relevant
      minor histocompatibility antigens. Compared to other gender combinations, female
      donor/male recipient (FDMR) transplants are associated with increased graft
      versus-host disease (GvHD), increased transplant-related mortality (TRM) and
      reduced risk of relapse. Still, their relative impact on transplant outcome
      remains controversial. We analyzed donor/recipient sex combination in 53,988
      patients treated with allogeneic hematopoietic stem cell transplantation (HSCT)
      between 1980 and 2005. We found a strong increase in chronic GvHD and late TRM
      and decreased survival in FDMR transplants irrespective of underlying disease.
      Conversely, FDMR patients had lower relapse rates. The negative effect on
      survival decreased with advancing disease stage as relapse protection became more
      important. Effects of H-Y alloreactivity were most pronounced in patients
      transplanted from HLA-matched donors and in those receiving transplants from an
      adult donor. Adjustment for acute and chronic GvHD only partially corrected the
      effects of H-Y alloreactivity. Analysis of the FDMR proportion over time
      indicated that the frequency of this gender combination has declined in unrelated
      transplants over the last 10 years. These data define the role of H-Y mismatching
      in allogeneic HSCT and support the current practice of avoiding female donors for
      male patients, if possible.

PMID- 18828774
TI  - Successful three-way kidney paired donation with cross-country live donor
      allograft transport.
AB  - Providing transplantation opportunities for patients with incompatible live
      donors through kidney paired donation (KPD) is seen as one of the important
      strategies for easing the crisis in organ availability. It has been estimated
      that an additional 1000-2000 transplants per year could be accomplished if a
      national KPD program were implemented in the United States. While most of these
      transplants could be arranged within the participants' local or regional area,
      patients with hard-to-match blood types or broad HLA sensitization would benefit
      from matching across larger geographic areas. In this case, either patients or
      organs would need to travel in order to obtain maximum benefit from a national
      program. In this study, we describe how a triple KPD enabled a highly sensitized
      patient (PRA 96%) to receive a well-matched kidney from a live donor on the
      opposite coast. The kidney was removed in San Francisco and transported to
      Baltimore where it was reperfused 8 h later. The patient had prompt function and
      1 year later has a serum creatinine of 1.1 mg/dl. This case provides a blueprint
      for solving some of the complexities that are inherent in the implementation of a
      national KPD program in a large country like the United States.

PMID- 18828775
TI  - Some issues in facial transplantation.
AB  - Human facial transplantation, a form of composite tissue allotransplantation, has
      now become a clinical reality. We carried out the world's second partial facial
      transplantation in April 2006. We reviewed some issues associated with facial
      transplantation, especially focusing on the individual who underwent the
      transplant in our department. We discussed surgical indications, techniques,
      risks versus benefits, informed consent and psychosocial, societal and financial
      issues of facial transplantation. In our opinion, with the progresses in
      composite tissue allotransplantation, partial or full facial transplantation is
      becoming a timely and effective remedy for the significantly disfigured patients.
      However, there are a lot of problems unsolved, and as we have performed the
      transplant on only three individuals, no long-term outcome data are available.
      Facial transplantation needs further research.

PMID- 18828776
TI  - Severe renal vein stenosis of a kidney transplant with beneficial clinical course
      after successful percutaneous stenting.
AB  - A 51-year-old renal transplant recipient presented with marked renal function
      deterioration 13 months after renal transplantation. After exclusion of ureteral
      obstruction, transplant artery stenosis and acute rejection, the diagnosis of a
      severe renal vein stenosis was made by an MR scan. After angiographic
      confirmation of the stenosis, treatment was attempted with percutaneous stent
      angioplasty. The long-term clinical course was favorable, with marked improvement
      in renal function. Transplant renal vein stenosis is a rare, but potentially
      curable, cause of renal allograft functional deterioration.

PMID- 18828779
TI  - A review on coping mechanisms against obesity bias in physical activity/education
      settings.
AB  - Obesity bias such as teasing or weight criticism during physical activity can
      lead to psychological or emotional damage for overweight or obese individuals.
      The literature indicates that the adverse effects of stigmatization on overweight
      or obese individuals can be mediated by coping mechanisms. However, little is
      known about how overweight or obese children and adolescents cope with weight
      stigma in physical activity/education settings. This paper provides a conceptual
      analysis of coping mechanisms through reviewing work on weight stigma in
      psychology literature and discusses the future research directions. The most
      promising areas for future research include conducting an in-depth qualitative
      exploration of overweight or obese individuals' coping mechanisms against obesity
      bias and studying potential individual and situational factors as moderating
      variables in physical activity/education settings.

PMID- 18828780
TI  - A hybrid zone provides evidence for incipient ecological speciation in Heliconius
      butterflies.
AB  - In Heliconius butterflies, it has been proposed that speciation occurs through a
      combination of divergence in ecological habitat preferences and mimetic colour
      patterns. Here we test this hypothesis by investigating a parapatric form of the
      widespread species Heliconius erato. Mendelian (colour patterns) and molecular
      genetic data permit us to address hypotheses about introgression and genetic
      differentiation between different populations. Combined analysis of colour
      pattern, microsatellite loci and mitochondrial DNA showed that Heliconius erato
      venus and Heliconius erato chestertonii form a bimodal hybrid zone implying
      partial reproductive isolation. In a sample of 121 individuals collected in
      sympatry, 25% were hybrids representing a significant deficit of heterozygotes
      compared to the Hardy-Weinberg expectation. Seven microsatellite loci, analysed
      for a subset of these individuals, showed marked differentiation between the
      parental taxa, and unambiguously identified two genotypic clusters concordant
      with our phenotypic classification of individuals. Mitochondrial DNA analysis
      showed H. erato venus as a monophyletic group well differentiated from H. erato
      chestertonii, implying a lack of historical introgression between the
      populations. Heliconius erato chestertonii is therefore an incipient species that
      maintains its integrity despite high levels of hybridization. Moreover, H. erato
      chestertonii is found at higher altitudes than other races of H. erato and has a
      distinct colour pattern and mimetic relationship. Hence, there are now two
      examples of parapatric incipient species related to H. erato, H. himera and H.
      erato chestertonii, both of which are associated with higher altitudes, more arid
      habitats and distinct mimetic relationships. This implies that parapatric habitat
      adaptation is a likely cause of speciation in this group.

PMID- 18828781
TI  - Sex-biased natal dispersal and inbreeding avoidance in American black bears as
      revealed by spatial genetic analyses.
AB  - We tested the hypothesis that sex-biased natal dispersal reduces close inbreeding
      in American black bears, a solitary species that exhibits nearly complete male
      dispersal and female philopatry. Using microsatellite DNA and spatial data from
      reproductively mature bears (>or= 4 years old), we examined the spatial genetic
      structure of two distinct populations in New Mexico from 1993 to 2000. As
      predicted, relatedness (r) and the frequency of close relationships (parent
      offspring or full siblings) decreased with distance among female dyads, but
      little change was observed among male or opposite-sex dyads. Neighbouring females
      were more closely related than neighbouring males. The potential for inbreeding
      was low. Most opposite-sex pairs that lived sufficiently close to facilitate
      mating were unrelated, and few were close relatives. We found no evidence that
      bears actively avoided inbreeding in their selection of mates from this nearby
      pool, as mean r and relationship frequencies did not differ between potential and
      actual mating pairs (determined by parentage analysis). These basic patterns were
      apparent in both study areas despite a nearly two-fold difference in density.
      However, the sex bias in dispersal was less pronounced in the lower-density area,
      based on proportions of bears with male and female relatives residing nearby.
      This result suggests that male bears may respond to reduced competition by
      decreasing their rate or distance of dispersal. Evidence supports the hypothesis
      that inbreeding avoidance is achieved by means of male-biased dispersal but also
      indicates that competition (for mates or resources) modifies dispersal patterns.

PMID- 18828782
TI  - The limits of mtDNA phylogeography: complex patterns of population history in a
      highly structured Iberian lizard are only revealed by the use of nuclear markers.
AB  - Phylogeographic analyses based on the sole use of the mitochondrial DNA (mtDNA)
      molecule reveal only a small part of the evolutionary history of a species or a
      set of related species. In this study, we have combined the application of slow-
      and fast-evolving nuclear markers (proteins and microsatellites, respectively)
      together with the analysis of two-gene genealogies to further understand the
      history of the Iberian endemic Schreiber's green lizard, Lacerta schreiberi, a
      species for which a well established phylogeographical scenario is available. In
      sharp contrast with the observation of four divergent and almost allopatric mtDNA
      clades, our nuclear data revealed how two groups of populations diverged,
      persisted and began to admix along the mountains of the Iberian Central System.
      In addition, the combination of mtDNA and nuclear data showed how the core area
      of the species distribution responded to ice ages, first by relatively old
      processes of population expansion to the south followed by episodes of
      contraction that are at the origin of present-day isolates, and more recently by
      a postglacial expansion to the Iberian Northwest where new habitats were made
      available after climatic amelioration. Taken together with recently published
      results for a variety of other organisms, our results suggest that complex
      processes of fragmentation, expansion and admixture can only be properly
      addressed through the use of several and complementary types of molecular
      markers. Finally, we also suggest that southern European refugia are both
      hotspots and melting pots of genetic diversity.

PMID- 18828783
TI  - Prognosis following non-surgical second treatment in patients with recurrent
      hepatocellular carcinoma after percutaneous ablation therapy.
AB  - OBJECTIVE: The aims of this study were to identify prognostic factors in patients
      who received a non-surgical second treatment for the development of recurrent
      hepatocellular carcinoma (HCC) after an initial percutaneous ablation therapy.
      METHODS: We retrospectively studied 147 patients with HCC who had received an
      initially successful percutaneous ablation therapy. The patients were followed up
      using computed tomography and/or ultrasound every 3 months and a second treatment
      was performed for subsequent recurrent tumours. RESULTS: The 3- and 5-year
      survival rates of the 147 patients were 90 and 65% respectively. During a mean
      follow-up period of 33 months, local or distant tumour recurrences developed in
      77 of the 147 patients, and the 3- and 5-year survival rates after a second
      treatment in these 77 patients were 73 and 44% respectively. Forty-six of the 77
      patients with up to three recurrent tumours received percutaneous ablation
      therapy for the second treatment, and the remaining 31 patients with more than
      three (multiple) recurrent tumours received transcatheter arterial
      chemoembolization for their second treatment. A multivariate analysis revealed
      the serum alpha-fetoprotein level at the time of the appearance of the recurrent
      HCC (<100 ng/ml vs >or=100 ng/ml, P=0.009) and the number of recurrent tumours
      (up to three vs more than three, P=0.009) to be independent prognostic factors
      after the second treatment. CONCLUSIONS: The serum alpha-fetoprotein level and
      recurrent tumour number were prognostic factors following the second treatment in
      patients with recurrent HCC who had received an initially successful ablation
      therapy.

PMID- 18828784
TI  - Anaphylactic shock in a young woman with abnormal liver scans.

PMID- 18828785
TI  - Hepatocellular adenomas.

PMID- 18828786
TI  - Elevated glutathione production by adding precursor amino acids coupled with ATP
      in high cell density cultivation of Candida utilis.
AB  - AIMS: Three precursor amino acids and adenosine triphosphate (ATP) are necessary
      for fermentative production of glutathione. In this study, our aims were to
      develop a strategy to enhance glutathione production by adding three precursor
      amino acids coupled with ATP in high cell density (HCD) cultivation of Candida
      utilis. METHODS AND RESULTS: A high-glutathione yeast strain, C. utilis WSH 02
      08, was used in this study. Whole fermentative process for glutathione production
      was divided into two phases of cell growth and glutathione synthesis. Cells
      concentration was increased by HCD cultivation. Meanwhile, intracellular
      glutathione content was enhanced by the addition of three precursor amino acids.
      Concentrations of three precursor amino acids added at stationary phase were
      optimized by response surface methodology. Moreover, the addition of ATP 15 h
      after the addition of the three amino acids can further enhance glutathione
      production. Based on aforementioned phenomenon, a strategy of adding three
      precursor amino acids coupled with ATP was developed to enhance glutathione
      production. CONCLUSION: Without the addition of three precursor amino acids and
      the ATP, a total glutathione of 1123 mg l(-1) was achieved after 60-h
      cultivation. In comparison, addition of three precursor amino acid counterparts
      resulted in a total glutathione of 1841 mg l(-1). Moreover, by adding amino acids
      combined with ATP, a total glutathione of 2043 mg l(-1) was achieved after 72-h
      cultivation, increased by 81.9% and 11%, respectively, as compared with the
      control and the one without ATP addition. SIGNIFICANCE AND IMPACT OF THE STUDY:
      This is the first report on investigating changes of the intracellular three
      precursor amino acids and ATP, and gamma-glutamylcysteine synthase activity in
      HCD cultivation of C. utilis for glutathione production. A strategy of combining
      addition of three precursor amino acids with ATP was developed to enhance
      glutathione production in C. utilis.

PMID- 18828787
TI  - Effect of gamma radiation on heat shock protein expression of four foodborne
      pathogens.
AB  - AIMS: The effects of gamma radiation on three heat shock proteins (Hsps) (GroEL,
      DnaK and GroES) synthesis in two Gram-negative (Escherichia coli and Salmonella
      serotype Typhimurium) and two Gram-positive (Staphylococcus aureus and Listeria
      monocytogenes) bacteria were investigated. METHODS AND RESULTS: The bacterial
      strains were treated with three radiation doses to induce cell damage, to obtain
      a viable but nonculturable state, and to cause cell death. Western blot analysis
      and quantification of Hsps in bacteria were performed immediately after
      irradiation treatment. In the four foodborne pathogens, GroEL was strongly
      induced by gamma rays in a dose-dependent manner, confirming the involvement of
      this protein in the cellular response to the stress generated by ionizing
      radiation. In addition, it was found that E. coli exposed to gamma radiation
      showed a significantly induction of DnaK and GroES proteins when compared with
      nonirradiated bacteria, whereas a GroES slight induction and a DnaK inhibition
      were observed in Salm. Typhimurium. CONCLUSIONS: The gamma rays influence the
      synthesis of Hsps in foodborne pathogen in a way that critically depends on the
      radiation dose. SIGNIFICANCE AND IMPACT OF THE STUDY: The study of stress
      response to several radiation doses was undertaken to elucidate how bacteria can
      survive in harsh conditions and cope with gamma radiation used to control
      foodborne pathogens and to characterize their adaptative response to this
      treatment.

PMID- 18828788
TI  - Efficient production and partial characterization of aspartyl aminopeptidase from
      Aspergillus oryzae.
AB  - AIMS: Aspartyl aminopeptidase (DAP) has a high degree of substrate specificity,
      degrading only amino-terminal acidic amino acids from peptides. Therefore,
      attention is focused here on the efficient production of this enzyme by a
      recombinant Aspergillus oryzae and characterization of its biochemical
      properties. METHODS AND RESULTS: The gene encoding DAP was overexpressed under a
      taka-amylase gene promoter, with His-tag linker in A. oryzae, during cultivation
      in a Co(2+)-containing medium. The enzyme was extracted from the mycelia and
      purified with immobilized nickel ion absorption chromatography using a buffer
      containing cobalt ion and imidazole. The active fraction was further purified
      with gel filtration chromatography. The resultant, electrophoretically pure
      enzyme displayed a molecular mass of 520 kDa. This enzyme displayed high
      reactivity towards peptide substrate rather than synthetic substrates.
      CONCLUSIONS: Recombinant A. oryzae DAP was purified to homogeneity with an
      increased specific activity, when cultivated in a Co(2+)-rich medium. Moreover,
      the use of suitable metal ions in microbial cultivation and purification
      processes may help in increasing the specific activity of other metalloproteases
      and their functional analysis. SIGNIFICANCE AND IMPACT OF THE STUDY: Recombinant
      DAP produced using a cobalt ion in culture media of A. oryzae and purification
      process allow high yield of the enzyme activity.

PMID- 18828789
TI  - Deciphering kas operon locus in Mycobacterium aurum and genesis of a recombinant
      strain for rational-based drug screening.
AB  - AIMS: To generate a recombinant Mycobacterium aurum strain for screening of
      antimycobacterial compounds affecting fatty acid synthase type II (FAS-II)
      elongation pathway. METHODS AND RESULTS: kas operon locus was delineated in M.
      aurum, a fast growing nonpathogenic strain. Cloning and sequencing all the genes
      of the operon showed similar organization and sequence similarities with
      Mycobacterium tuberculosis (H37Rv) orthologues. Further, we cloned the upstream
      region of M. tuberculosis kas operon in fusion with lacZ reporter gene and put it
      in M. aurum. Recombinant M. aurum strain showed continued expression of reporter
      gene throughout the growth while an increased expression of the reporter gene was
      noticed only after treatment with FAS-II pathway inhibitors. Swapping of the
      regulatory sequence aborts the increased reporter gene expression after same
      antibiotic treatments. CONCLUSIONS: kas operon genes are similarly organized in
      M. tuberculosis and M. aurum. H37Rv kas operon promoter upregulates the reporter
      gene expression in M. aurum only upon treatment with drugs inhibiting FAS-II
      pathway. SIGNIFICANCE AND IMPACT OF THE STUDY: It would serve as a good second
      line screen for characterization of compounds showing antimycobacterial activity
      in a first-line screen. With the simplicity of beta-galactosidase enzyme assay
      the system can be easily adapted in high-throughput mode.

PMID- 18828790
TI  - In vitro effects of phosphatidylcholine and transgalactooligosaccharides on the
      production of 1,2-sn-diacylglycerol by Bifidobacterium longum biovar infantis.
AB  - AIMS: To investigate the production of the tumour promoter 1,2-sn-diacylglycerol
      (DAG) by a human gut isolate of Bifidobacterium longum biovar infantis. METHODS
      AND RESULTS: Bifidobacterium longum biovar infantis was grown in vitro using
      anaerobic static batch cultures in the presence of phosphatidylcholine (PC) and
      trans-galactooligosaccharides (TOS). Production of DAG was found to be dependent
      upon the presence of PC, while TOS had a reducing effect. Considerable
      differences in morphology, growth and metabolic end products from the micro
      organism were observed under the different culture conditions. CONCLUSIONS: Our
      results have provided evidence that B. longum biovar infantis can produce DAG in
      vitro and that a prebiotic exerted a reducing effect upon this production.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The results presented in this study
      demonstrate an ability of ostensibly beneficial member of the colonic environment
      to produce unwanted compounds under certain conditions. Therefore, it may be
      important that a combination of substrates and other factors are assessed when
      studying the behaviour of any bacterial group or species, especially when
      designing the dietary interventions.

PMID- 18828791
TI  - OmpA is an adhesion factor of Aeromonas veronii, an optimistic pathogen that
      habituates in carp intestinal tract.
AB  - AIMS: In the present study, we focused on one of the Aeromonas veronii isolates
      that exhibited marked adhesion onto carp intestine and studied its membrane
      associated proteins for their possible involvement in mucosal adhesion. METHODS
      AND RESULTS: We isolated a strain of Aer. veronii (CWP11) that exhibited a high
      degree of temperature-dependent adhesion activity onto carp intestinal tract and
      studied its adhesion factor. A proteomic analysis of the membrane-associated
      fraction showed the presence of multiple proteins that were specifically
      expressed in CWP11 cells cultured at 25 degrees C. Of these, a 30 kDa protein was
      identified to be OmpA by a mass fingerprint analysis. Cloning and nucleotide
      sequencing of the ompA region of CWP11 revealed the presence of two tandem ompA
      homologues (ompAI-ompAII). Escherichia coli that expressed either OmpAI or OmpAII
      exhibited marked adhesion onto carp intestinal surface. Disruption of ompAI by a
      homologous recombination technique resulted in marked reduction of the adhesion
      activity in CWP11. CONCLUSION: The OmpA homologue plays an important role in the
      adhesion of the Aer. veronii strain onto the surface of intestinal tract.
      SIGNIFICANCE AND IMPACT OF THE STUDY: We successfully identified an OmpA
      homologue to be an adhesion factor of Aer. veronii, an optimistic pathogen that
      habituates in carp intestinal tract.

PMID- 18828792
TI  - Purification and characterization of antibacterial substances produced by a
      marine bacterium Pseudoalteromonas haloplanktis strain.
AB  - AIMS: To purify and characterize compounds with antimicrobial activity from
      Pseudoalteromonas haloplanktis inhibition (INH) strain. METHODS AND RESULTS: The
      P. haloplanktis isolated from a scallop hatchery was used to analyse
      antibacterial activities. Crude extracts were obtained with ethyl acetate of the
      cultured broth, after separation of bacterial cells, and assays against six
      strains of marine bacteria and nine clinically important pathogenic bacteria. The
      active compounds were purified from ethyl acetate extracts, by a combination of
      SiO(2) column and thin layer chromatography. Two active fractions were isolated,
      and chemical structures of two products from the major one were unambiguously
      identified as isovaleric acid (3-methylbutanoic acid) and 2-methylbutyric acid (2
      methylbutanoic acid), by comparing their mass spectra and (1)H- and (13)C-nuclear
      magnetic resonance spectra to those of authentic compounds. CONCLUSIONS: In the
      antibacterial activity of P. haloplanktis INH strain, extra cell compounds are
      involucred, mainly isovaleric and 2-methylbutyric acids. SIGNIFICANCE AND IMPACT
      OF THE STUDY: Production of antimicrobial compounds by marine micro-organisms has
      been widely reported; however, the efforts not always are conducted to
      purification and applications of these active compounds. This study is a
      significant contribution to the knowledge of compounds unique from marine
      bacteria as potential sources of new drugs in the pharmacological industry.

PMID- 18828793
TI  - Long-term posaconazole treatment and follow-up of rhino-orbital-cerebral
      mucormycosis in a diabetic girl.
AB  - To demonstrate that the 2-yr clinical follow-up of our patient strongly suggests
      that long-term therapy with posaconazole (POS) is safe and beneficial in
      treatment and prevention of relapses of, otherwise fatal, central nervous system
      mucormycosis. Mucormycosis is a very rare opportunistic mycotic infection of
      diabetic children. We present the 30-month follow-up of a 12-yr-old girl affected
      by diabetic ketoacidotic coma, complicated by rhinocerebral mucormycosis and
      successfully treated with POS at the initial daily dose of 5 mg/kg t.i.d. with
      fatty food for 3 wk, followed by a daily dose of 10 mg/kg in four doses for 2
      months and then 20 mg/kg/d in four doses for 16 months and in two doses for
      further 5 months. The previous amphotericin B, granulocyte colony-stimulating
      factor, hyperbaric oxygen and nasal and left maxillary sinus surgical debridement
      therapy was ineffective in stopping the progression of the infection to the
      brain. The patient improved within 10 d with reduced ocular swelling and pain,
      and 6 months after therapy stop, she is in good health and cultures are sterile.
      This article demonstrates that POS may be a useful drug in mucormycosis in
      children. We also strongly draw the attention to the main preventive procedure
      against invasive fungal infection that is the correct management of antidiabetic
      therapy that prevents the predisposing temporary neutrophils activity deficit,
      contributing to a better survival rate of diabetic children.

PMID- 18828794
TI  - Altered molecular adaptation to exercise in children with type 1 diabetes: beyond
      hypoglycemia.

PMID- 18828796
TI  - Age at first drink and the first incidence of adult-onset DSM-IV alcohol use
      disorders.
AB  - BACKGROUND: Existing studies of the association between age at first drink (AFD)
      and the risk of alcohol use disorders (AUD) suffer from inconsistent levels of
      control and designs that may inflate associations by failure to control for
      duration of exposure to risk. METHODS: This study examined associations between
      AFD (ages <15 and 15-17 vs. 18+ years) and first incidence of DSM-IV alcohol
      dependence, abuse, and specific AUD criteria over a 3-year follow-up in a
      longitudinal study of U.S. drinkers 18 years of age and older at baseline (n =
      22,316), controlling for duration of exposure, family history, and a wide range
      of baseline and childhood risk factors. RESULTS: After adjusting for all risk
      factors, the incidence of dependence was increased for AFD <15 years (OR = 1.38)
      and for women only with AFD at ages 15 to 17 (OR = 1.54). The incidence of abuse
      was increased at AFD <15 and 15 to 17 years (OR = 1.52 and 1.30, respectively).
      Most dependence criteria showed significant associations with AFD, but hazardous
      drinking and continued drinking despite interpersonal problems were the only
      abuse criteria to do so. All associations were nonsignificant after controlling
      for volume of consumption, except that AFD at all ages <18 combined was
      associated with a reduced likelihood of impaired control, and AFD at ages 15 to
      17 was associated with lower odds of drinking more/longer than intended among
      heavy-volume drinkers. In a population of low-risk drinkers that excluded those
      with positive family histories, personality disorders, and childhood risk
      factors, there were strong associations between early AFD (<18) and the incidence
      of dependence (OR = 3.79) and continued drinking despite physical/psychological
      problems (OR = 2.71), but no association with incidence of abuse. CONCLUSIONS:
      There is a robust association between AFD and the risk of AUD that appears to
      reflect willful rather than uncontrolled heavy drinking, consistent with misuse
      governed by poor decision-making and/or reward-processing skills associated with
      impaired executive cognitive function (ECF). Additional research is needed to
      determine causality in the role of impaired ECF, including longitudinal studies
      with samples of low-risk adolescents.

PMID- 18828795
TI  - Growth factor control of pancreatic islet regeneration and function.

PMID- 18828797
TI  - Effects of alcoholism typology on response to naltrexone in the COMBINE study.
AB  - BACKGROUND: This study investigated whether subgroups of alcohol-dependent
      patients responded differently to naltrexone versus placebo in the NIAAA COMBINE
      study. In particular, the A versus B and the Early Onset versus Late Onset
      typologies were examined. Relative to Type A alcoholics, Type B alcoholics are
      characterized by greater severity, earlier onset, stronger family history, more
      childhood risk factors (e.g., conduct disorder), and greater frequency of
      comorbid psychiatric and substance use disorders. METHODS: COMBINE study
      participants were categorized as Type A or Type B using k-means cluster analysis
      and variables from 5 domains that have been shown to replicate the original Babor
      typology efficiently. Early Onset was defined as alcohol dependence beginning
      before age 25. For the planned analyses, the sample was reduced to the 618
      participants receiving naltrexone alone or placebo, either with medical
      management (MM) alone or with MM plus the Combined Behavioral Intervention (CBI).
      The a priori primary outcome was percent heavy drinking days during treatment in
      the groups receiving MM without CBI. RESULTS: Among those receiving MM without
      CBI, Type A alcoholics had better drinking outcomes with naltrexone than placebo,
      whereas medication condition did not influence outcomes significantly in the Type
      Bs. Age of onset was not significantly related to outcome. For those receiving
      CBI, no significant effects were found for either typology. CONCLUSIONS: In this
      sample, the beneficial effects of opioid antagonism were limited to Type A
      alcoholics receiving treatment in a MM model. Future studies should investigate
      the relationship between clinically relevant genotypes, phenotypes such as
      typologies, and treatment response. More work is also needed to develop practical
      algorithms for phenotypic assignment.

PMID- 18828798
TI  - S-adenosyl-L-methionine co-administration prevents the ethanol-elicited
      dissociation of hepatic mitochondrial ribosomes in male rats.
AB  - BACKGROUND: Chronic ethanol feeding to male rats has been shown to result in
      decreased mitochondrial translation, depressed respiratory complex levels and
      mitochondrial respiration rates. In addition, ethanol consumption has been shown
      to result in an increased dissociation of mitoribosomes. S-adenosyl-L-methionine
      (SAM) is required for the assembly and subsequent stability of mitoribosomes and
      is depleted during chronic ethanol feeding. The ability of dietary SAM co
      administration to prevent these ethanol-elicited lesions was investigated.
      METHODS: Male Sprague-Dawley rats were fed a nutritionally adequate liquid diet
      with ethanol comprising 36% of the calories according to a pair-fed design for 28
      days. For some animals, SAM was supplemented in the diet at 200 mg/l. Liver
      mitochondria were prepared and mitoribosomes isolated. Respiration rates, ATP
      levels, respiratory complex levels, and the extent of mitoribosome dissociation
      were determined. RESULTS: Twenty-eight days of ethanol feeding were found to
      result in decreased SAM content, depressed respiration, and increased
      mitoribosome dissociation. No changes in mitochondrial protein content; levels of
      respiratory complexes I, III, and V; complex I activities; and ATP levels were
      detected. Co-administration of SAM in the diet was found to prevent ethanol
      induced SAM depletion, respiration decreases and mitoribosome dissociation.
      CONCLUSIONS: Taken together, these findings suggest (1) that mitoribosome
      dissociation precedes respiratory complex depressions in alcoholic animals and
      (2) that dietary supplementation of SAM prevents some of the early mitochondrial
      lesions associated with chronic ethanol consumption.

PMID- 18828799
TI  - Neuropsychological study of FASD in a sample of American Indian children:
      processing simple versus complex information.
AB  - BACKGROUND: Although a large body of literature exists on cognitive functioning
      in alcohol-exposed children, it is unclear if there is a signature
      neuropsychological profile in children with Fetal Alcohol Spectrum Disorders
      (FASD). This study assesses cognitive functioning in children with FASD from
      several American Indian reservations in the Northern Plains States, and it
      applies a hierarchical model of simple versus complex information processing to
      further examine cognitive function. We hypothesized that complex tests would
      discriminate between children with FASD and culturally similar controls, while
      children with FASD would perform similar to controls on relatively simple tests.
      METHODS: Our sample includes 32 control children and 24 children with a form of
      FASD [fetal alcohol syndrome (FAS) = 10, partial fetal alcohol syndrome (PFAS) =
      14]. The test battery measures general cognitive ability, verbal fluency,
      executive functioning, memory, and fine-motor skills. RESULTS: Many of the
      neuropsychological tests produced results consistent with a hierarchical model of
      simple versus complex processing. The complexity of the tests was determined "a
      priori" based on the number of cognitive processes involved in them.
      Multidimensional scaling was used to statistically analyze the accuracy of
      classifying the neurocognitive tests into a simple versus complex dichotomy.
      Hierarchical logistic regression models were then used to define the contribution
      made by complex versus simple tests in predicting the significant differences
      between children with FASD and controls. Complex test items discriminated better
      than simple test items. The tests that conformed well to the model were the
      Verbal Fluency, Progressive Planning Test (PPT), the Lhermitte memory tasks, and
      the Grooved Pegboard Test (GPT). The FASD-grouped children, when compared with
      controls, demonstrated impaired performance on letter fluency, while their
      performance was similar on category fluency. On the more complex PPT trials
      (problems 5 to 8), as well as the Lhermitte logical tasks, the FASD group
      performed the worst. CONCLUSIONS: The differential performance between children
      with FASD and controls was evident across various neuropsychological measures.
      The children with FASD performed significantly more poorly on the complex tasks
      than did the controls. The identification of a neurobehavioral profile in
      children with prenatal alcohol exposure will help clinicians identify and
      diagnose children with FASD.

PMID- 18828800
TI  - Alcohol withdrawal-induced hippocampal neurotoxicity in vitro and seizures in
      vivo are both reduced by memantine.
AB  - BACKGROUND: The ethanol withdrawal (EWD) syndrome is typically treated using
      benzodiazepines such as diazepam. However there is concern that benzodiazepines
      may not prevent neurotoxicity associated with EWD. Antagonists of glutamate/N
      Methyl-D-Aspartate receptors (NMDARs) such as MK801 have been shown to be
      effective against both EWD-induced neurotoxicity in vitro and seizures in vivo.
      However, most of these agents have adverse side effects. An exception is the
      moderate affinity NMDAR channel blocker memantine, used in Alzheimer's dementia.
      The present studies examined the ability of memantine to protect against EWD
      related toxicity in vitro and seizures in vivo. METHODS: Organotypic hippocampal
      slice cultures from neonatal rat pups were treated starting at 15 days in vitro
      with 100 mM ethanol for 10 days followed by a 24-hour EWD period. During the 24
      hour EWD period cultures were treated with memantine (15 or 30 microM). MK801 (10
      microM) was utilized as a positive control. For the in vivo studies, the ability
      of memantine (2, 5, 10, and 15 mg/kg) to reduce convulsions was analyzed in Swiss
      Webster mice using the handling induced convulsion test paradigm. RESULTS: In
      vitro studies demonstrated that memantine is effective at blocking EWD-induced
      neurotoxicity. In vivo experiments showed that memantine also significantly
      reduced convulsions induced by EWD in mice. CONCLUSIONS: Memantine may be of
      therapeutic value during alcohol detoxification by virtue of its having
      neuroprotective effects in addition to anti-seizure activity. The potential role
      of memantine in treatment of alcoholism is deserving of further study.

PMID- 18828801
TI  - Haplotypic variants in DRD2, ANKK1, TTC12, and NCAM1 are associated with comorbid
      alcohol and drug dependence.
AB  - BACKGROUND: Each gene in the chromosome 11q23 cluster of NCAM1, TTC12, ANKK1, and
      DRD2 is functionally linked to dopamine in brain. Many association studies of
      DRD2 and substance dependence (SD), including alcohol dependence (AD) and drug
      dependence (DD), have been reported; the results have been inconsistent. Recent
      association studies have considered this cluster more comprehensively, examining
      the association of SD with several risk variants mapped to the other genes in the
      cluster. Because comorbid AD with DD (AD+DD) is common, we hypothesized that
      heterogeneity of the SD diagnoses studied might have contributed to the
      inconsistency of prior results. METHODS: We conducted 2 separate association
      studies of AD+DD and AD without DD (AD-only) in 1,090 European-Americans using
      family-based and case-control designs and 43 single nucleotide polymorphisms
      mapped to this cluster. We used a generalized linear model and haplotype score
      tests for the case-control sample, and the family-based association test for the
      family sample. RESULTS: For AD+DD, the risk regions centered on TTC12 exon 3
      [optimal individual haplotype simulated p (p(oihs)) = 0.000015], and another
      extended from ANKK1 exon 8 to DRD2;C957T (p(oihs) = 0.0028), in both samples.
      NCAM1 exon 12 markers showed global significance in both designs, but were
      significant for specific haplotypes (p(oihs) = 0.0029) only for the family
      sample. For AD-only, NCAM1 intron 14 to 18 and the junction of ANKK1 and DRD2
      were associated globally. Population stratification was excluded as the basis for
      these results. Linkage disequilibrium contrast tests supported selection at TTC12
      exon 3 and ANKK1 exon 2. CONCLUSIONS: We conclude that variants in TTC12 exon 3,
      NCAM1 exon 12, and the two 3'-ends of ANKK1 and DRD2 co-regulate risk for
      comorbid AD and DD.

PMID- 18828802
TI  - Effects of the glucocorticoid antagonist, mifepristone, on the consequences of
      withdrawal from long term alcohol consumption.
AB  - BACKGROUND: Studies were carried out to test the hypothesis that administration
      of a glucocorticoid Type II receptor antagonist, mifepristone (RU38486), just
      prior to withdrawal from chronic alcohol treatment, would prevent the
      consequences of the alcohol consumption and withdrawal in mice. MATERIALS AND
      METHODS: The effects of administration of a single intraperitoneal dose of
      mifepristone were examined on alcohol withdrawal hyperexcitability. Memory
      deficits during the abstinence phase were measured using repeat exposure to the
      elevated plus maze, the object recognition test, and the odor
      habituation/discrimination test. Neurotoxicity in the hippocampus and prefrontal
      cortex was examined using NeuN staining. RESULTS: Mifepristone reduced, though
      did not prevent, the behavioral hyperexcitability seen in TO strain mice during
      the acute phase of alcohol withdrawal (4 hours to 8 hours after cessation of
      alcohol consumption) following chronic alcohol treatment via liquid diet. There
      were no alterations in anxiety-related behavior in these mice at 1 week into
      withdrawal, as measured using the elevated plus maze. However, changes in
      behavior during a second exposure to the elevated plus maze 1 week later were
      significantly reduced by the administration of mifepristone prior to withdrawal,
      indicating a reduction in the memory deficits caused by the chronic alcohol
      treatment and withdrawal. The object recognition test and the odor habituation
      and discrimination test were then used to measure memory deficits in more detail,
      at between 1 and 2 weeks after alcohol withdrawal in C57/BL10 strain mice given
      alcohol chronically via the drinking fluid. A single dose of mifepristone given
      at the time of alcohol withdrawal significantly reduced the memory deficits in
      both tests. NeuN staining showed no evidence of neuronal loss in either
      prefrontal cortex or hippocampus after withdrawal from chronic alcohol treatment.
      CONCLUSIONS: The results suggest mifepristone may be of value in the treatment of
      alcoholics to reduce their cognitive deficits.

PMID- 18828803
TI  - Gender and age at drinking onset affect voluntary alcohol consumption but neither
      the alcohol deprivation effect nor the response to stress in mice.
AB  - BACKGROUND: Epidemiological studies suggest that initiation of alcohol drinking
      at an early age is associated with an increased risk of developing an alcohol use
      disorder later in life. Nevertheless, relatively few studies using animal models
      have investigated the relationship between age of onset of drinking and ethanol
      drinking patterns in adulthood. Besides age at drinking onset, other factors such
      as gender could also affect the pattern of development of alcohol consumption. In
      rodents, many studies have shown that females drink more than males. However,
      even if it is assumed that hormonal changes occurring at puberty could explain
      these differences, only one study performed in rats has investigated the
      emergence of sex-specific alcohol drinking patterns in adolescence and the
      transition from adolescence to adulthood. The aim of the present study was to
      compare the acquisition of voluntary alcohol consumption, relapse-like drinking
      (the Alcohol Deprivation Effect-ADE) and stress-induced alcohol drinking in male
      and female outbred mice that acquired alcohol consumption during adolescence or
      adulthood. METHODS: Separate groups of naive female and male WSC-1 mice aged +/-
      28 days (adolescents) or +/-70 days (adults) were given ad libitum access to
      water and 6% ethanol solution for 8 weeks (1st to 8th week) before undergoing a 2
      week deprivation phase (9th and 10th week). After the deprivation period, 2
      bottle preference testing (ethanol vs. water) resumed for 3 weeks (11th to 13th).
      During the 13th week, all animals were subjected to restraint stress for 2
      consecutive days. RESULTS: Over the entire time course of the experiment, ethanol
      intake and preference increased in females (both adults and adolescents).
      Adolescent animals (both females and males) showed a transient increase in
      alcohol consumption and preference compared to adults. However, by the end of
      continuous alcohol exposure (when all mice were adults), ethanol intake was not
      affected by age at drinking onset. A deprivation phase was followed by a rise in
      ethanol intake (ADE) that was not affected by sex or age. Finally, stress did not
      alter alcohol self-administration either during or after its occurrence.
      CONCLUSIONS: Emergence of greater alcohol consumption in adult females does not
      seem to be limited to a specific developmental period (i.e., puberty). Age of
      voluntary drinking onset (adolescence vs. adulthood) does not affect eventual
      alcohol intake in adult WSC-1 mice and does not modify the transient increase in
      ethanol consumption after alcohol deprivation.

PMID- 18828804
TI  - Relationship between ethanol's acute locomotor effects and ethanol self
      administration in male Long-Evans rats.
AB  - BACKGROUND: Human studies have suggested an important relationship between
      ethanol sensitivity and risk of alcoholism. These studies have led some to
      hypothesize that a low initial sensitivity to ethanol's depressant effects and/or
      an elevated response to ethanol's stimulant effects may represent important risk
      factors associated with the development of abusive drinking behavior.
      Unfortunately, elucidating neurobiologic mechanisms that may underlie these
      relationships between ethanol sensitivity and ethanol drinking have been hampered
      by difficulties in modeling some of these interactions in animals. In this study,
      we re-examined some of these relationships in an outbred strain of rats using
      continuous access two-bottle choice drinking and a limited-access operant
      procedure that engenders pharmacologically relevant levels of ethanol intake and
      permits the discrete assessment of appetitive and consummatory measures of
      ethanol drinking behavior. METHODS: Twenty-three male Long-Evans rats were
      habituated to a locomotor activity box and then tested for their response to a
      stimulant (0.5 g/kg) and depressant (1.5 g/kg) ethanol dose. Rats were then
      trained to complete a lever pressing requirement to gain access to 10% ethanol
      for 20-minute sessions conducted 5 d/wk for 5 weeks. Appetitive behavior was
      assessed after 2.5 and 4.5 weeks using 20-minute extinction trials in which
      ethanol was not presented and lever responses were recorded. Home-cage ethanol
      preference was also assessed prior to and immediately following the 5-week self
      administration regimen using a continuous access, two-bottle choice procedure.
      RESULTS: A significant increase in home-cage ethanol preference was observed
      following the self-administration procedure, however, neither measure of ethanol
      preference correlated with average daily ethanol intake during the operant self
      administration sessions or with initial sensitivity to ethanol's stimulant or
      depressant effects. Notably, a significant negative correlation was observed
      between sensitivity to ethanol's locomotor depressant effect and daily intake
      during the operant self-administration sessions. No significant relationships
      were noted between sensitivity to ethanol's locomotor effects and extinction
      responding. CONCLUSIONS: The results of these studies suggest that the well
      established relationship between a low level of response to ethanol and increased
      ethanol consumption reported in human studies can be observed in an outbred
      rodent strain using a limited-access operant self-administration procedure, but
      not with home-cage ethanol drinking.

PMID- 18828805
TI  - Nondaily smoking and alcohol use, hazardous drinking, and alcohol diagnoses among
      young adults: findings from the NESARC.
AB  - BACKGROUND: Nondaily smoking and heavy alcohol use are prevalent behaviors among
      young adults, with nondaily smoking occurring primarily in the context of alcohol
      use. Although the relationship between drinking and daily smoking has been well
      characterized in young adults, few epidemiological investigations have
      investigated the association between nondaily smoking and drinking behavior.
      METHODS: We examined Wave 1 of the National Epidemiologic Survey on Alcohol and
      Related Conditions (NESARC; Grant et al., 2003b; n = 43,093). Young adults (aged
      18 to 25 years; n = 5,838) were stratified on current smoking behavior (daily,
      nondaily, and nonsmokers in the past 12 months) and differences in weekly
      quantity of alcohol use, frequency of alcohol use, frequency of binge drinking
      behavior, rates of NIAAA-defined hazardous drinking, and rates of DSM-IV alcohol
      diagnoses were investigated. College student status was examined. RESULTS: Twenty
      five percent were current smokers and 7% were smoking on a nondaily basis.
      Seventy-one percent were current drinkers, 39% reported binge drinking at least
      once a month, 41% met criteria for hazardous drinking, and 18% had alcohol use
      disorders. Across all measures of alcohol use, there was a significant effect of
      smoking status, with daily smokers having greater alcohol use patterns, compared
      with nondaily smokers, with nonsmokers consuming the least. Nondaily smokers were
      more likely to report any binge drinking in the past 12 months. However, daily
      smokers were more likely to report daily binge drinking. With regard to hazardous
      drinking and alcohol use disorders, nondaily smoking conferred the greatest risk,
      followed by daily smoking with nonsmoking as the reference group. Multinomial
      logistic regression demonstrated that the odds of being a hazardous drinker were
      16 times greater (95% CI 9.46-26.48) in a nondaily smoker compared with a
      nonsmoker, whereas the odds for a daily smoker were increased by 7-fold (95% CI
      5.54-9.36). A similar pattern of results was demonstrated for DSM-IV alcohol
      diagnoses. No differences across college student status were observed.
      CONCLUSIONS: The increased risk of hazardous drinking and alcohol use disorders
      conferred by nondaily smoking supports the findings that nondaily smoking and
      drinking are highly concomitant behaviors. Results such as these suggest that
      interventions disengaging alcohol and cigarette use patterns (e.g., smoking bans
      in alcohol venues) might serve to limit the occurrence of hazardous drinking
      among young adults at heightened risk for this behavior.

PMID- 18828806
TI  - Alterations in ethyl alcohol pharmacokinetics during oral consumption of malt
      liquor beverages in African Americans.
AB  - BACKGROUND: Malt liquor (ML) beverages have become increasingly popular among
      urban minority groups, due partly to their inexpensive price and targeted
      advertising. We hypothesized that nonfermented by-products contained in ML
      beverages will alter the pharmacokinetics (PK) and pharmacodynamic (PD) effects
      of its ethanol content. In addition, we determined the effect of alcohol
      dehydrogenase (ADH) genotypes on the PK following consumption of ML beverages.
      METHODS: The study was conducted in 31 healthy adult African-American social
      drinkers, mean +/- SD age of 22.3 +/- 1.3 years, and weight of 70.7 +/- 10.9 kg.
      Participants were administered ethanol, in randomized order, 2-weeks apart, in
      the form of oral ML beverage (6%v/v), or isocaloric solution of diet soda-ethanol
      (DS-Etoh) beverage (6%v/v). During each session the beverage was consumed over 4
      minutes and breath alcohol concentrations (BrAC) as well as subjective and
      behavioral effects of ethanol were evaluated over 180 minutes. Pharmacokinetic
      parameters of ethanol were calculated using Michaelis-Menten elimination
      kinetics. The effect of ML and ADH genotype on PK was evaluated using the
      Wilcoxon rank-sum test and the Wilcoxon signed rank test, respectively. RESULTS:
      Results show a slower mean rate of absorption, K(a), (0.12 vs. 0.15 min(-1), p =
      0.03) and a longer time to reach maximum concentration, T(max), (28 vs. 23
      minute, p < 0.01) for the ML compared with DS-Etoh beverage. The ML beverage
      resulted in a larger area under the BrAC-time curve compared with DS-Etoh
      beverage (8.4 vs. 6.8 min g/dl, p = 0.02). There was no difference in the
      subjective PD effects between the 2 beverages. CONCLUSION: Results show that
      exposure to ethanol following the consumption of ML beverages is different
      compared to that following nonmalt beverages in African-Americans. These
      differences may be related to nonfermented by-products present in commercially
      available ML products. These PK differences do not appear to result in
      significant perceived alcohol PD changes, nor are they related to ADH genotype.

PMID- 18828808
TI  - Association of pro-ghrelin and GHS-R1A gene polymorphisms and haplotypes with
      heavy alcohol use and body mass.
AB  - BACKGROUND: Ghrelin, an orexigenic peptide, acts on growth hormone secretagogue
      receptors (GHS-R1A), expressed in the hypothalamus as well as in important reward
      nodes such as the ventral tegmental area. Interestingly, ghrelin has been found
      to activate an important part of the reward systems, i.e., the cholinergic
      dopaminergic reward link. Additionally, the rewarding and neurochemical
      properties of alcohol are, at least in part, mediated via this reward link. There
      is comorbidity between alcohol dependence and eating disorders. Thus, plasma
      levels of ghrelin are altered in patients with addictive behaviors such as
      alcohol and nicotine dependence and in binge eating disorder. This overlap
      prompted as to investigate the pro-ghrelin and GHS-R1A genes in a haplotype
      analysis of heavy alcohol-using individuals. METHODS: A total of 417 Spanish
      individuals (abstainers, moderate, and heavy alcohol drinkers) were investigated
      in a haplotype analysis of the pro-ghrelin and GHS-R1A genes. Tag SNPs were
      chosen using HapMap data and the Tagger and Haploview softwares. These SNPs were
      then genotyped using TaqMan Allelic Discrimination. RESULTS: SNP rs2232165 of the
      GHS-R1A gene was associated with heavy alcohol consumption and SNP rs2948694 of
      the same gene as well as haplotypes of both the pro-ghrelin and the GHS-R1A genes
      were associated with body mass in heavy alcohol consuming individuals.
      CONCLUSIONS: The present findings are the first to disclose an association
      between the pro-ghrelin and GHS-R1A genes and heavy alcohol use, further
      strengthening the role of the ghrelin system in addictive behaviors and brain
      reward.

PMID- 18828807
TI  - Differential effects of acute alcohol on prepulse inhibition and event-related
      potentials in adolescent and adult Wistar rats.
AB  - BACKGROUND: Previous studies have demonstrated that adolescent and adult rats
      show differential sensitivity to many of the acute effects of alcohol. We
      recently reported evidence of developmental differences in the effects of acute
      alcohol on the cortical electroencephalogram. However, it is unclear whether
      developmental differences are also observed in other neurophysiological and
      neurobehavioral measurements known to be sensitive to alcohol exposure. The
      present study determined the age-related effects of acute alcohol on behavioral
      and event-related potential (ERP) responses to acoustic startle (AS) and prepulse
      inhibition (PPI). METHODS: Male adolescent and adult Wistar rats were implanted
      with cortical recording electrodes. The effects of acute alcohol (0.0, 0.75, and
      1.5 g/kg) on behavioral and ERP responses to AS and PPI were assessed. RESULTS:
      Acute alcohol (0.75 and 1.5 g/kg) significantly reduced the behavioral and
      electrophysiological response to AS in adolescent and adult rats. Both 0.75 and
      1.5 g/kg alcohol significantly enhanced the behavioral response to PPI in
      adolescent, but not in adult rats. During prepulse + pulse trials, 1.5 g/kg
      alcohol significantly increased the N10 pulse response in the adolescent frontal
      cortex. Acute alcohol (0.75 and 1.5 g/kg) also increased the N1 ERP pulse
      response to prepulse stimuli in frontal and parietal cortices in adult rats, but
      not in adolescent rats. CONCLUSIONS: These data suggest that alcohol's effect on
      behavioral and electrophysiological indices of AS do not differ between adults
      and adolescents whereas developmental stage does appear to significantly modify
      alcohol-influenced response to PPI.

PMID- 18828809
TI  - Relationship between the hypothalamic-pituitary-thyroid axis and alcohol craving
      in alcohol-dependent patients: a longitudinal study.
AB  - BACKGROUND: A relationship between some hypothalamic-pituitary-related hormones
      and craving for alcohol has been suggested, leading to hypothesize a role of some
      hormones in the neurobiology of alcohol dependence. Investigating this
      association in alcohol-dependent (AD) patients was the aim of this preliminary
      and exploratory study. METHODS: Cortisol, adrenocorticotropic hormone, prolactin,
      thyroid-stimulating hormone (TSH), free T3, free T4, growth hormone, follicle
      stimulating hormone, luteinizing hormone as well as administering the Obsessive
      Compulsive Drinking Scale (OCDS) and Penn Alcohol Craving Scale (PACS) were
      assessed at baseline and after 12 weeks in 25 current AD patients. Patients were
      treated with baclofen (10 mg t.i.d.) for these 12 weeks. Sixteen patients
      remained totally abstinent for 12 weeks. RESULTS: At baseline, a significant
      inverse correlation was found between TSH and PACS (r = -0.46; p = 0.022) and
      OCDS scores (r = -0.53; p = 0.007). A significant direct correlation was found
      between free T3 and OCDS score (r = 0.44; p = 0.026). In the 16 abstinent
      patients, craving scores were significantly decreased at 12 weeks (p < 0.01). At
      12 weeks, no significant correlation was found between TSH and craving, but free
      T3 remained directly correlated with OCDS score (r = 0.60; p = 0.013).
      CONCLUSIONS: A relationship between alcohol craving and free T3 and TSH was
      demonstrated in AD patients, suggesting the potential involvement of the
      hypothalamic-pituitary-thyroid axis in the neurobiology of alcohol craving.

PMID- 18828810
TI  - Learning in the 2-bottle alcohol preference test.
AB  - BACKGROUND: The 2-bottle preference test is a popular protocol for characterizing
      a rodent's selection of a variety of solutions. Little attention has been paid,
      however, to the role of learning in this procedure. METHODS: We explored the role
      of learning in 2-bottle alcohol preference (AP) in mice by recording changes
      between days and periods (every 3 days the alcohol and water tubes were
      interchanged) throughout a 15-day standard exposure protocol in use in our
      laboratory. RESULTS: Male and female ethanol-naive mice of 2 BALB strains (cJ and
      cByJ), both characterized by low AP scores in the 2-bottle test, exhibited
      decreases in AP among days but the magnitude of the change depended on test
      period: relatively large reductions in AP between Day 1 and the subsequent 2 days
      of the first 3-day test period, smaller decreases between days during Period 2,
      while there were no significant differences between days during Periods 3 and 4.
      Thus, the ability of the mice to adapt to changes in tube position improved with
      increasing experience with the test until asymptote was reached. Study of mice
      from a C57BL/6JXBALB/cCrgl intercross with a wide range of AP scores showed that
      learning in the 2-bottle test was not restricted to inbred animals. In this
      genetically heterogeneous group, learning was shown to be flexible according to
      an animal's idiosyncratic pattern of alcohol intake: mice characterized by low AP
      scores on the basis of their 15-day mean AP index exhibited decreases across Days
      and Periods similar to those shown by the BALB mice (who also had low alcohol
      consumption) but F(2) mice characterized by high overall AP scores exhibited
      increases in AP across Periods. CONCLUSIONS: Two-bottle AP scores are known to be
      affected by genetic influences and environmental variation before test
      administration. The present data provide evidence of learning within the 2-bottle
      test situation and this phenomenon may help understand the biobehavioral
      mechanisms underlying preference behavior.

PMID- 18828812
TI  - Composition of supra- and subgingival biofilm of subjects with healthy and
      diseased implants.
AB  - OBJECTIVES: The purpose of this study was to compare the microbial composition of
      supra- and subgingival biofilm in subjects with and without peri-implantitis.
      MATERIAL AND METHODS: Forty-four subjects (mean age 48.9 +/- 13.51 years) with at
      least one implant restored and functional for at least 2 years were assigned to
      two groups: a peri-implantitis group (n=22), consisting of subjects presenting
      peri-implant sites with radiographic defects >3 mm, bleeding on probing and/or
      suppuration; and a control group (n=22), consisting of subjects with healthy
      implants. The clinical parameters evaluated were plaque index, gingival bleeding,
      bleeding on probing, suppuration, probing depth and clinical attachment level.
      Supra- and subgingival biofilm samples were taken from the deepest sites of each
      implant and analyzed for the presence of 36 microorganisms by checkerboard DNA
      DNA hybridization. RESULTS: Higher mean counts of Porphyromonas gingivalis,
      Treponema denticola and Tannerella forsythia were observed in the peri
      implantitis group, both supra- and subgingivally (P<0.05). The proportions of the
      pathogens from the red complex were elevated, while host-compatible beneficial
      microbial complexes were reduced in diseased compared with healthy implants. The
      microbiological profiles of supra- and subgingival environments did not differ
      substantially within each group. CONCLUSION: Marked differences were observed in
      the composition of supra- and subgingival biofilm between healthy and diseased
      implants. The microbiota associated with peri-implantitis was comprised of more
      periodontal pathogenic bacterial species, including the supragingival biofilm.

PMID- 18828811
TI  - Neuropeptide Y receptor genes are associated with alcohol dependence, alcohol
      withdrawal phenotypes, and cocaine dependence.
AB  - BACKGROUND: Several lines of evidence in both human and animal studies suggest
      that variation in neuropeptide Y (NPY) or its receptor genes (NPY1R, NPY2R and
      NPY5R) is associated with alcohol dependence as well as alcohol withdrawal
      symptoms. Additional studies suggest that cocaine may affect NPY expression.
      METHODS: A total of 39 single nucleotide polymorphisms (SNPs) were genotyped
      across NPY and its 3 receptor genes in a sample of 1,923 subjects from 219
      multiplex alcoholic families of European American descent recruited as part of
      the Collaborative Studies on the Genetics of Alcoholism (COGA) study. Family
      based association analysis was performed to test the primary hypothesis that
      variation in these genes is associated with alcohol dependence. Secondary
      analyses evaluated whether there was an association of these SNPs with symptoms
      of alcohol withdrawal, cocaine dependence, or comorbid alcohol and cocaine
      dependence. RESULTS: Although variations in NPY itself were not associated with
      these phenotypes, variations in 2 NPY-receptor genes were. SNPs in NPY2R provided
      significant evidence of association with alcohol dependence, alcohol withdrawal
      symptoms, comorbid alcohol and cocaine dependence, and cocaine dependence (all p
      < 0.03). Haplotype analyses strengthened the evidence for these phenotypes
      (global 0.0004 < p < 0.005). SNPs in NPY5R demonstrated significant association
      with alcohol withdrawal characterized by seizures (p < 0.05). CONCLUSION: These
      results indicate that sequence variations in NPY receptor genes are associated
      with alcohol dependence, particularly a severe subtype of alcohol dependence
      characterized by withdrawal symptoms, comorbid alcohol and cocaine dependence,
      and cocaine dependence.

PMID- 18828813
TI  - Bone level changes at implants supporting crowns or fixed partial dentures with
      or without cantilevers.
AB  - OBJECTIVE: The aim of this study was to analyze whether or not a cantilever
      extension on a fixed dental prosthesis (FDP) supported by implants increased the
      amount of peri-implant bone loss or technical complications compared with
      reconstructions without cantilevers. MATERIALS AND METHODS: Fifty-four partially
      dentate patients with a total of 54 FDPs supported by 78 implants were enrolled
      in the study. Twenty-seven FDPs were with cantilever and 27 FDPs were without
      cantilever (control group). All FDPs were supported by one or two implants and
      were located in the posterior maxilla or mandible. The primary outcome variable
      was change in peri-implant marginal bone level from the time of FDP placement to
      the last follow-up visit. FDPs were under functional loading for a period of 3 up
      to 12.7 years. Statistical analysis was carried out with Student's t-test.
      Regression analyses were carried out to evaluate the influence of confounding
      factors on the peri-implant bone level change. In addition, implant survival
      rates were calculated and technical complications assessed. RESULTS: After a mean
      observation period of 5.3 years, the mean peri-implant bone loss for the FDPs
      with cantilevers was 0.23 mm (SD+/-0.63 mm) and 0.09 mm (SD+/-0.43 mm) for FDPs
      without cantilever. Concerning the bone level change at implants supporting FDPs
      with or without cantilevers no statistically significant differences were found.
      The regression analysis revealed that jaw of implant placement had a
      statistically significant influence on peri-implant bone loss. When the bone loss
      in the cantilever group and the control group were compared within the maxilla or
      mandible separately, no statistically significant difference was found. Implant
      survival rates reached 95.7% for implants supporting cantilever prostheses and
      96.9% for implants of the control group. Five FDPs in the cantilever group showed
      minor technical complications, none were observed in the control group.
      CONCLUSION: Within the limitations of this study it was concluded that cantilever
      on FDPs did not lead to a higher implant failure rate and did not lead to more
      bone loss around supporting implants compared with implants supporting
      conventional FDPs. In contrast to these results more technical complications were
      observed in the group reconstructed with cantilever.

PMID- 18828814
TI  - Clinical analysis of the soft tissue integration of non-submerged (ITI) and
      submerged (3i) implants: a prospective-controlled cohort study.
AB  - AIM: The aim of this study was to compare the soft tissue integration of
      submerged and non-submerged implants by means of periodontal parameter
      assessments and analysis. MATERIAL AND METHODS: Thirty-one patients, who received
      42 non-submerged implants (ITI) and 48 submerged implants (3i), participated in
      the study. There was no significant difference (P>0.05) between both groups
      considering gender; educational level; handedness; toothbrushing frequency; the
      number of auxiliary devices used; and smoking habits. The parameters assessed
      were gingival index (GI), plaque index (PII), retention index (RI), pocket
      probing depth (PPD) and keratinized mucosa index. RESULTS: At evaluation, 66.67%
      of all sites showed a GI of 0; 72.22% a PI of 0, and 93.33% the absence of
      calculus. The average PPD was 2.56 mm in the non-submerged and 2.70 mm in the
      submerged group. With regard to the width of keratinized mucosa, 100% of the ITI
      implants showed a band of keratinized gingiva around the implant, whereas 14.58%
      in the 3i group showed a complete absence of keratinized mucosa. The intra
      examiner reproducibility was 90.96% for all parameters and the Kendall tau-b
      analysis showed a powerless correlation between the chosen parameters for both
      studied groups. CONCLUSIONS: The study material showed no major differences
      between submerged and non-submerged dental implants regarding GI, PII, RI and
      PPD, except the width of keratinized mucosa. Regarding the presence of
      keratinized mucosa, there is a need for further longitudinal studies to elucidate
      a possible benefit of one implant system over the other.

PMID- 18828815
TI  - Spontaneous progression of peri-implantitis at different types of implants. An
      experimental study in dogs. I: clinical and radiographic observations.
AB  - AIM: The aim of the present study was to analyze tissue reactions to plaque
      formation following ligature removal at commercially available implants exposed
      to experimental peri-implantitis. MATERIAL AND METHODS: Six Labrador dogs about 1
      year old were used. All mandibular premolars and the three anterior premolars in
      both sides of the maxilla were extracted. After 3 months four implants
      representing four different implant systems with different surface
      characteristics--implant group A (turned), B (TiOblast), C (sandblasted acid
      etched; SLA) and D (TiUnite)--were placed in a randomized order in the right side
      of the mandible. Three months after implant installation experimental peri
      implantitis was initiated by placement of ligatures in a submarginal position and
      plaque accumulation. At week 12, when about 40-50% of the supporting bone was
      lost, the ligatures were removed. During the subsequent 24-week period plaque
      accumulation continued. Radiographic and clinical examinations were performed
      during the 'active breakdown' period (plaque accumulation and ligatures) and the
      plaque accumulation period after ligature removal. The experiment was terminated
      at week 36. RESULTS: The bone loss that took place during the 'active breakdown'
      period varied between 3.5 and 4.6 mm. The additional bone loss that occurred
      during the plaque accumulation period after ligature removal was 1.84 (A), 1.72
      (B), 1.55 (C) and 2.78 mm (D). CONCLUSION: Spontaneous progression of
      experimentally induced peri-implantitis occurred at implants with different
      geometry and surface characteristics. Progression was most pronounced at implants
      of type D (TiUnite surface).

PMID- 18828816
TI  - Angiogenesis in newly augmented bone observed in rabbit calvarium using a
      titanium cap.
AB  - OBJECTIVES: In our previous work using a rabbit experimental model, we identified
      the importance of using a rigid support device for augmenting the development of
      mineralized bone. In the early stage of healing, newly generated tissue has not
      filled occlusive spaces, and mineralized bone forms and tends to climb along the
      inner wall of a device. Even though the blood supply is critical for successful
      bone augmentation, few studies have been conducted on angiogenesis in augmented
      bone. The purpose of the present study was to evaluate a method for observing
      angiogenesis in newly augmented bone. MATERIAL AND METHODS: The right and left
      sections of the calvarium of six adult male Japanese white rabbits were exposed.
      The cortical bone was penetrated, and custom-made, standardized, hemispherical
      titanium caps were fixed to the exposed bone. The caps on the right side of each
      rabbit were filled with granulated beta-tricalcium phosphate (beta-TCP). After a
      healing period of 1 month, the animals were injected with MICROFIL into the right
      and left common carotid arteries to form a three-dimensional cast of the
      vasculature, and the newly generated blood vessels in the augmented bone were
      observed. RESULTS: The newly generated blood vessels were observed entering the
      space beyond the existing calvarial bone. Furthermore, angiogenesis was seen to
      have occurred to a similar extent through the inter-granular beta-TCP in the
      right caps. These areas of angiogenesis were observed in a histological study
      with cross-sections. CONCLUSIONS: The results of the present study suggest that
      this observation method allows the examination of angiogenesis in hard tissue
      before the preparation of histological specimens.

PMID- 18828817
TI  - Calvarial bone regeneration by a combination of natural anorganic bovine-derived
      hydroxyapatite matrix coupled with a synthetic cell-binding peptide (PepGen): an
      experimental study in rats.
AB  - OBJECTIVES: The aim of this study was to evaluate histologically the effect of
      natural anorganic bovine-derived hydroxyapatite matrix (ABM) coupled with a
      synthetic cell-binding peptide on the healing of critical size calvarial defects
      in rats. MATERIAL AND METHODS: Sixteen 4-month-old rats were used in the study. A
      5 mm trephine defect was created in each parietal bone of every animal. One
      defect was left untreated (control) while the contralateral defect was treated
      with a natural ABM coupled with a synthetic cell-binding peptide (test). At 60
      and 120 days post-operatively, groups of eight animals were sacrificed and 7-10
      microm-thick decalcified sections were produced from both test and control sides.
      Three sections, 100 mum apart, representing the central area of each defect were
      selected for the histometric analysis. RESULTS: Histological analysis showed
      limited bone formation in both control and test defects at both observation
      periods. The control defects healed with fibrous connective tissue occupying the
      midportion of the defect and minimal new bone formation at the periphery. In the
      test defects, the major part of the defect was occupied by graft particles
      embedded in connective tissue. After 60 days of healing the residual defects
      accounted up to 94.6% of the original defect dimensions in the control specimens
      and 90.6% in the test specimens. The differences between test and control defects
      were not statistically significant (P=0.06). After 120 days of healing, the
      residual defects accounted up 89.9% of the original defect dimensions in the
      control specimens and 85% in the test specimens. The difference was not
      statistically significant (P=0.33). CONCLUSION: The ABM coupled with a synthetic
      cell-binding peptide failed to substantially promote new bone formation in rat
      calvarial defects.

PMID- 18828818
TI  - Immunohistochemical characterization of nanocrystalline hydroxyapatite silica gel
      (NanoBone(r)) osteogenesis: a study on biopsies from human jaws.
AB  - OBJECTIVES: Bone substitute biomaterials may be osteogenic, osteoconductive or
      osteoinductive. To test for these probable characteristics in a new nanoporous
      grafting material consisting of nanocrystalline hydroxyapatite embedded in a
      porous silica gel matrix (NanoBone(s)), applied in humans, we studied biopsies
      from 12 patients before dental implantation following various orofacial
      augmentation techniques with healing times of between 3.5 and 12 months. MATERIAL
      AND METHODS: Sections from decalcified specimens were investigated using
      histology, histochemistry [periodic acid Schiff, alcian blue staining and
      tartrate-resistant acid phosphatase (TRAP)] and immunohistochemistry, with
      markers for osteogenesis, bone remodelling, resorption and vessel walls (alkaline
      phosphatase, bone morphogenetic protein-2, collagen type I, ED1, osteocalcin,
      osteopontin, runx2 and Von-Willebrand factor). RESULTS: Histologically, four
      specific stages of graft transformation into lamellar bone could be
      characterized. During early stages of healing, bone matrix proteins were absorbed
      by NanoBone(s) granules, forming a proteinaceous matrix, which was invaded by
      small vessels and cells. We assume that the deposition of these molecules
      promotes early osteogenesis in and around NanoBone(s) and supports the
      concomitant degradation probably by osteoclast-like cells. TRAP-positive
      osteoclast-like cells were localized directly on the granular surfaces. Runx2
      immunoreactive pre-osteoblasts, which are probably involved in direct
      osteogenesis forming woven bone that is later transformed into lamellar bone,
      were attracted. Graft resorption and bone apposition around the graft granules
      appear concomitantly. CONCLUSIONS: We postulate that NanoBone(s) has
      osteoconductive and biomimetic properties and is integrated into the host's
      physiological bone turnover at a very early stage.

PMID- 18828819
TI  - Alveolar ridge augmentation using implants coated with recombinant human bone
      morphogenetic protein-2: radiographic observations.
AB  - OBJECTIVES: Effective carrier technologies and dosing appear critical for the
      successful use of bone morphogenetic proteins (BMPs). This study evaluated
      radiographically the potential of a purpose-designed titanium porous-oxide
      implant surface combined with recombinant human BMP-2 (rhBMP-2) to stimulate
      alveolar ridge augmentation. MATERIAL AND METHODS: Twelve young-adult Labrador
      dogs were used. Three 10-mm titanium implants per jaw quadrant were placed 5 mm
      into the alveolar ridge following extraction of the premolar teeth and reduction
      of alveolar ridge. Six animals received implants coated with rhBMP-2 at 0.75 or
      1.5 mg/ml randomized to contralateral jaw quadrants. Another six animals received
      implants coated with rhBMP-2 at 3 mg/ml or uncoated control using the same split
      mouth design. The mucoperiosteal flaps were advanced, adapted, and sutured to
      submerge the implants. Radiographic registrations were made immediately
      postsurgery (baseline), and at weeks 4 and 8 (end of study). RESULTS: rhBMP-2
      coated implants exhibited robust radiographic bone formation extending to and
      above the implant platform from week 4 (P<0.01). Some rhBMP-2-coated implants
      showed voids within the newly formed bone that gradually resolved and/or implant
      displacement, being severe in two animals receiving implants coated with rhBMP-2
      at 3 mg/ml. Controls showed limited, if any, new bone formation at weeks 4 and 8
      postsurgery. There were no significant differences among the rhBMP-2 groups in
      bone gain. CONCLUSIONS: The titanium porous-oxide surface serves as an effective
      carrier for rhBMP-2, showing a clinically significant potential to stimulate
      local bone formation. With the carrier technology used, therapeutic dosage
      appears to be in the range of 0.75-1.5 mg/ml.

PMID- 18828820
TI  - Performance of dental implants after staged sinus floor elevation procedures: 5
      year results of a prospective study in partially edentulous patients.
AB  - OBJECTIVES: The aim of this prospective study was to evaluate the 5-year
      performance and success rate of titanium screw-type implants with the titanium
      plasma spray (TPS) or the sand-blasted, large grit, acid-etched (SLA) surface
      inserted in a two-stage sinus floor elevation (SFE) procedure in the posterior
      maxilla. MATERIAL AND METHODS: A total of 59 delayed SFEs were performed in 56
      patients between January 1997 and December 2001, using a composite graft with
      autogenous bone chips combined with deproteinized bovine bone mineral (DBBM) or
      synthetic porous beta-tricalcium phosphate (beta-TCP). After a healing period
      averaging 7.75 months, 111 dental implants were inserted. After an additional 8
      14-week healing period, all implants were functionally loaded with cemented
      crowns or fixed partial dentures. The patients were recalled at 12 and 60 months
      for clinical and radiographic examination. RESULTS: One patient developed an
      acute infection in the right maxillary sinus after SFE and did not undergo
      implant therapy. Two of the 111 inserted implants had to be removed because of a
      developing atypical facial pain, and 11 implants were lost to follow-up and were
      considered drop-outs. The remaining 98 implants showed favorable clinical and
      radiographic findings at the 5-year examination. The peri-implant soft tissues
      were stable over time; the mean probing depths and mean attachment levels did not
      change during the follow-up period. The measurement of the bone crest levels (DIB
      values) indicated stability as well. Based on strict success criteria, all 98
      implants were considered successfully integrated, resulting in a 5-year success
      rate of 98% (for TPS implants 89%, for SLA implants 100%). CONCLUSION: This
      prospective study assessing the performance of dental implants inserted after SFE
      demonstrated that titanium implants can achieve and maintain successful tissue
      integration with high predictability for at least 5 years of follow-up in
      carefully selected patients.

PMID- 18828821
TI  - Maxillary sinus-floor elevation: an animal model.
AB  - OBJECTIVES: To find an animal model for modified Caldwell-Luc procedure training.
      The animal model should have (1) a proper cortical thickness in the lateral wall;
      (2) a similar morphology and resistance of the Schneiderian membrane in humans;
      and, finally, (3) an oral approach. MATERIALS AND METHODS: Twelve fresh heads
      (four Merino sheep, four Murciano-Granadina goats and four Large-White pigs). Two
      skulls from each of these species were also used. Several three-dimensional
      imagings from the skulls of each species were acquired using a C-arm. Two fresh
      heads of each species were used to perform the modified Caldwell-Luc procedure.
      Two fresh heads of each species were firstly frozen at -30 degrees C for 48 h and
      then sawed in blocks containing only the target region of the maxillary sinus.
      RESULTS: The average thickness was 2.03 mm in goat and sheep and 2.80 in pig.
      Releasing and elevation of the Schneiderian membrane from the sinus floor were
      easy in the three species. The approach of the maxillary sinus in sheep, goat and
      pig from the buccal vestibule required a previous surgical enlargement of the
      buccal vestibule. CONCLUSIONS: In conclusion, the cortical bone thickness and
      Schneider membrane characteristics in Merina sheep and Murciano-Granadina goat
      allow a perfect training for the modified Caldwell-Luc procedure. However, the
      approach from the oral cavity needs, in these species, a previous enlargement of
      the buccal vestibule. The excessive thickness of the cortical bone restricts the
      use of pigs for this technique.

PMID- 18828822
TI  - Orthodontic loading of titanium miniplates in dogs: microradiographic and
      histological evaluation.
AB  - OBJECTIVES: The objectives of this animal study were to evaluate if orthodontic
      loading has an impact on osseointegration of screws supporting miniplates, and to
      describe the histological components of the bone-screw interface. MATERIALS AND
      METHODS: Eighty orthodontic miniplates were placed in the jaws of 10 dogs. After
      2 weeks, a 125 g force was applied between the miniplates of one upper quadrant
      of each dog and between those of the controlateral lower quadrant. The others,
      nonloaded miniplates, were considered as controls. Five dogs were sacrificed 7
      weeks after implantation and the remaining five dogs after 29 weeks [Short Term
      (ST) and Long Term (LT) groups, respectively]. Fluorochromes were injected at
      implantation and at sacrifice. Jaw quadrants were dissected, embedded, cut into
      undecalcified transverse sections through the screws and finally submitted to
      microradiographic analysis to allow assessment of bone-implant contact (BIC) and
      bone volume/total volume (BV/TV). The sections were observed under UV light and
      stained in order to examine them under ordinary light. RESULTS: Osseointegration
      occurred around 90/160 screws and consisted mainly in limited repair and
      remodelling processes of lamellar bone, without inflammation. Wide variations
      were observed in BIC and BV/TV, but without any significant difference, neither
      between the loaded and the nonloaded screws, nor according to the direction of
      load, whereas they were significantly higher in the LT than in the ST group.
      Nonosseointegrated screws were surrounded by fibrous tissue. Osteoblastic
      activity, when present in front of these screws, was not sufficient to achieve
      stability. CONCLUSIONS: Osseointegration underlying orthodontic anchorage was not
      affected by loading. BIC increased with time and varied according to implantation
      site. Particularly the tight-fitting screw insertion appeared crucial in
      determining the appropriate bone healing response.

PMID- 18828823
TI  - Orthodontic load on short maxillary implants with reduced sink depth: an
      experimental study.
AB  - OBJECTIVE: The aim of this study was to investigate experimentally the positional
      stability and histomorphometric findings of length-reduced temporary anchorage
      devices (Orthosystem, length: 4 mm) with reduced sink depth. MATERIAL AND
      METHODS: For this purpose, four maxillary pre-molars ((2)P(2), (3)P(3)) were
      extracted from each of four foxhounds. After a 16-week alveolar healing period,
      16 implants (four per dog) were inserted into the edentulous areas. Four implants
      (one per dog) were placed simultaneously in the mid-palatal area. The implants
      were intentionally submerged to about three-quarters of their length. After a 10
      week unloaded implant healing period, the implants in the P3 areas and the palate
      were loaded (test implants) by means of transpalatal bars fixed on the implants
      in the P3 areas and Sentalloy traction springs ( approximately 2 N continuous
      force) inserted mid-sagittally between palatal implants and bars (force
      application period: 24 weeks). The implants in the P2 areas served as controls.
      RESULTS: Clinical measurements and histological evaluation revealed positional
      stability of the loaded fixtures. Alveolar control implants (ACI) were inserted
      to a mean depth of 3.2 mm, alveolar test implants (ATI) to 3.3 mm and palatal
      test implants (PTI) to 2.6 mm. The mean direct bone contact percentage values
      were 71.3% (ACI), 79.6% (ATI) and 72.2% (PTI). CONCLUSION: These results suggest
      that, probably due to the relatively high percentage of bone contact with implant
      surface, only 3 mm of intrabony implant length is sufficient to retain positional
      stability during long-term orthodontic loading.

PMID- 18828824
TI  - One-year outcome of narrow diameter blasted implants for rehabilitation of
      maxillas with knife-edge resorption.
AB  - OBJECTIVES: This study aimed at assessing the clinical outcome of narrow diameter
      implants in the treatment of knife-edge edentulous maxillas of adequate bone
      height but inadequate width (class IV of Cawood and Howell). MATERIAL AND
      METHODS: Twelve consecutive patients (eight women and four men, mean age 58
      years) with class IV atrophic edentulous maxillas were included in the study.
      Seventy-three microthreaded TiO(2)-blasted implants were placed and the resonance
      frequency measured. All the implants had a diameter of 3.5 mm. After 6 months of
      submerged healing, fixed implant-supported prostheses were delivered to the
      patients and resonance frequency and radiographic examinations performed. After
      the first year of loading, the implant outcome was again evaluated clinically,
      radiographically and with resonance frequency analysis. RESULTS: All the implants
      were followed up to 1 year of loading and their survival rate was 100%. Bone loss
      after 1 year of loading was (mean+/-SD) 0.30+/-0.13 mm. Stability values were
      (mean+/-SD) 63+/-5.8 ISQ at placement, 60+/-4.7 ISQ at the abutment connection
      and 61+/-5 ISQ after 1 year of loading. A significant difference resulted between
      placement and abutment connection values (P=0.03). CONCLUSIONS: According to the
      present study, narrow implants may be used to restore edentulous maxillas with
      atrophies of class IV of Cawood and Howell. When planning the treatment of
      edentulous maxillas with such a resorption pattern, this possibility has to be
      considered as an alternative to more demanding grafting techniques.

PMID- 18828825
TI  - Long-term results of mandibular reconstruction with autogenous bone grafts and
      oral implants after tumor resection.
AB  - OBJECTIVES: (a) To evaluate retrospectively the clinical outcome of non
      vascularized bone grafts used for the reconstruction of mandibular defects
      following tumor resection; (b) to evaluate the clinical outcome of implants and
      implant-supported prostheses placed in the reconstructed areas; and (c) to
      evaluate patients' satisfaction regarding function and esthetics after oral
      rehabilitation. MATERIAL AND METHODS: In a 9-year period (1995-2003), 29 patients
      affected by mandibular tumors involving to tooth bearing areas were treated by
      means of tumor resection and immediate or delayed reconstruction with autogenous
      non-revascularized calvarial or iliac bone grafts. Among these patients, 16
      patients were selected for dental rehabilitation of the lost dentition with
      implant-supported 3fixed prosthese333s. For to 7 months later, the patients
      received 60 oral implants for the prosthetic rehabilitation of the reconstructed
      edentulous areas. RESULTS: No total failure of the graft was observed, while
      partial loss of the graft was observed in one patient. The mean follow-up of
      patients after the start of prosthetic loading of implants treated was 94 months
      (range: 36-132 months). Two patients dropped out of the follow-up after 3 and 4
      years of observation, respectively. Two implants were removed due to loss of
      osseointegration, while two implants, although still integrated, presented peri
      implant bone resorption values higher than those proposed by Albrektsson et al.
      for successful implants. Cumulative survival and success rates of implants were
      96.7% and 93.3%, respectively. CONCLUSION: Results from this study demonstrated
      that bone defects following resection of mandibular tumors can be predictably
      reconstructed with autogenous bone grafts taken from the calvarium or the
      anterior iliac crest. It has also been shown that the long-term survival and
      success rates of implants placed in the reconstructed areas (96.7% and 93.3%,
      respectively) may guarantee an excellent prognosis of implant-supported
      prostheses.

PMID- 18828826
TI  - Electromyographic analysis of masticatory and neck muscles in subjects with
      natural dentition, teeth-supported and implant-supported prostheses.
AB  - OBJECTIVES: To compare the electromyographic (EMG) characteristics of masticatory
      and neck muscles in patients with natural dentition, teeth-supported prostheses
      and implant-supported prostheses. MATERIALS AND METHODS: Twenty-five subjects
      aged 40-80 years were examined. Five patients had maxillary and mandibular
      implant-supported fixed prostheses; five patients had mandibular implant
      supported fixed prosthesis and maxillary removable complete denture; seven
      patients had implant-supported fixed prosthesis (one arch) and natural dentition
      or full-arch tooth-fixed prosthesis (one arch); and eight control subjects had
      natural dentition or single tooth-fixed prostheses. Surface EMG of masseter,
      temporal and sternocleidomastoid muscles was performed during maximum teeth
      clenching and unilateral gum chewing. Interarch dental contacts were assessed
      with shim stocks. RESULTS: All groups had similar interarch dental contacts
      (P>0.05). During clenching, patients with maxillary and mandibular implant
      supported fixed prostheses had unbalanced standardized masseter and temporalis
      anterior activities (74%), with significantly larger values found in the other
      patients and control subjects (all mean values larger than 86%, P=0.017). All
      patients chewed with significantly larger muscular potentials than control
      subjects (on average, 1434-2100 microV s vs. 980 microV s, P=0.04), and had
      altered muscular patterns (left side, P=0.021). The patients with one arch with
      natural dentition/tooth fixed prostheses had chewing muscular patterns similar to
      the control subjects. CONCLUSIONS: Clenching with the analyzed prostheses was
      performed with a relative increment of temporalis activity. Neuromuscular
      coordination during chewing was larger in patients who maintained their teeth or
      dental roots, independently from the number of dental contacts.

PMID- 18828827
TI  - The leading scientific forum for implant dentistry in Europe.

PMID- 18828828
TI  - Does team training work? Principles for health care.
AB  - Teamwork is integral to a working environment conducive to patient safety and
      care. Team training is one methodology designed to equip team members with the
      competencies necessary for optimizing teamwork. There is evidence of team
      training's effectiveness in highly complex and dynamic work environments, such as
      aviation and health care. However, most quantitative evaluations of training do
      not offer any insight into the actual reasons why, how, and when team training is
      effective. To address this gap in understanding, and to provide guidance for
      members of the health care community interested in implementing team training
      programs, this article presents both quantitative results and a specific
      qualitative review and content analysis of team training implemented in health
      care. Based on this review, we offer eight evidence-based principles for
      effective planning, implementation, and evaluation of team training programs
      specific to health care.

PMID- 18828830
TI  - Defining team performance for simulation-based training: methodology, metrics,
      and opportunities for emergency medicine.
AB  - Across health care, teamwork is a critical element for effective patient care.
      Yet, numerous well-intentioned training programs may fail to achieve the desired
      outcomes in team performance. Hope for the improvement of teamwork in health care
      is provided by the success of the aviation and military communities in utilizing
      simulation-based training (SBT) for training and evaluating teams. This consensus
      paper 1) proposes a scientifically based methodology for SBT design and
      evaluation, 2) reviews existing team performance metrics in health care along
      with recommendations, and 3) focuses on leadership as a target for SBT because it
      has a high likelihood to improve many team processes and ultimately performance.
      It is hoped that this discussion will assist those in emergency medicine (EM) and
      the larger health care field in the design and delivery of SBT for training and
      evaluating teamwork.

PMID- 18828831
TI  - Toward a definition of teamwork in emergency medicine.
AB  - The patient safety literature from the past decade emphasizes the importance of
      teamwork skills and human factors in preventing medical errors. Simulation has
      been used within aviation, the military, and now health care domains to
      effectively teach and assess teamwork skills. However, attempts to expand and
      generalize research and training principles have been limited due to a lack of a
      well-defined, well-researched taxonomy. As part of the 2008 Academic Emergency
      Medicine Consensus Conference on "The Science of Simulation in Healthcare," a
      subset of the group expertise and group assessment breakout sections identified
      evidence-based recommendations for an emergency medicine (EM) team taxonomy and
      performance model. This material was disseminated within the morning session and
      was discussed both during breakout sessions and via online messaging. Below we
      present a well-defined, well-described taxonomy that will help guide design,
      implementation, and assessment of simulation-based team training programs.

PMID- 18828832
TI  - Advanced medical simulation applications for emergency medicine microsystems
      evaluation and training.
AB  - Participants in the 2008 Academic Emergency Medicine Consensus Conference "The
      Science of Simulation in Healthcare: Defining and Developing Clinical Expertise"
      morning workshop session on developing systems expertise were tasked with
      evaluating best applications of simulation techniques and technologies to small
      scale systems in emergency medicine (EM). We collaborated to achieve several
      objectives: 1) describe relevant theories and terminology for discussion of
      health care systems and medical simulation, 2) review prior and ongoing efforts
      employing systems thinking and simulation programs in general medical sectors and
      acute care medicine, 3) develop a framework for discussion of systems thinking
      for EM, and 4) explore the rational application of advanced medical simulation
      methods to a defined framework of EM microsystems (EMMs) to promote a "quality-by
      design" approach. This article details the materials compiled and questions
      raised during the consensus process, and the resulting simulation application
      framework, with proposed solutions as well as their limitations for EM systems
      education and improvement.

PMID- 18828833
TI  - Teaching and assessing procedural skills using simulation: metrics and
      methodology.
AB  - Simulation allows educators to develop learner-focused training and outcomes
      based assessments. However, the effectiveness and validity of simulation-based
      training in emergency medicine (EM) requires further investigation. Teaching and
      testing technical skills require methods and assessment instruments that are
      somewhat different than those used for cognitive or team skills. Drawing from
      work published by other medical disciplines as well as educational, behavioral,
      and human factors research, the authors developed six research themes:
      measurement of procedural skills; development of performance standards;
      assessment and validation of training methods, simulator models, and assessment
      tools; optimization of training methods; transfer of skills learned on simulator
      models to patients; and prevention of skill decay over time. The article reviews
      relevant and established educational research methodologies and identifies gaps
      in our knowledge of how physicians learn procedures. The authors present
      questions requiring further research that, once answered, will advance
      understanding of simulation-based procedural training and assessment in EM.

PMID- 18828834
TI  - Use of case studies to promote interdisciplinary learning.

PMID- 18828835
TI  - The Mhc class II DRB genotype of Macaca fascicularis does not influence infection
      by simian retrovirus type 2.
AB  - Simian retrovirus type 2 (SRV-2) is a natural pathogen of Macaca fascicularis.
      Although SRV-2 may be endemic in macaque colonies, it is not necessarily detected
      in all individuals suggesting differential susceptibility to SRV-2; factors
      contributing to this susceptibility are not fully understood. We have
      investigated the role of host genetic origin on virus susceptibility. We have
      shown that high levels of anti-SRV-2 antibodies correlate with failure to
      establish persistent virus infection, thus we targeted our genetic analysis of
      virus susceptibility with an investigation of the role of the polymorphic macaque
      major histocompatibility complex (MHC) class II locus. DRB genotypes, both novel
      and previously characterised, were identified in individuals and family groups. A
      discordance with SRV-2 infection status suggests that an Mhc II DRB genotype is
      not overtly associated with the outcome of viral infection.

PMID- 18828836
TI  - Comparative analysis of circadian clock genes in insects.
AB  - After a slow start, the comparative analysis of clock genes in insects has
      developed into a mature area of study in recent years. Brain transplant or
      surgical interventions in larger insects defined much of the early work in this
      area, before the cloning of clock genes became possible. We discuss the evolution
      of clock genes, their key sequence differences, and their likely modes of
      regulation in several different insect orders. We also present their expression
      patterns in the brain, focusing particularly on Diptera, Lepidoptera, and
      Orthoptera, the most common non-genetic model insects studied. We also highlight
      the adaptive involvement of clock molecules in other complex phenotypes which
      require biological timing, such as social behaviour, diapause and migration.

PMID- 18828837
TI  - Identification and characterization of multiple Spidroin 1 genes encoding major
      ampullate silk proteins in Nephila clavipes.
AB  - Spider dragline silk is primarily composed of proteins called major ampullate
      spidroins (MaSps) that consist of a large repeat array flanked by nonrepetitive N
      and C-terminal domains. Until recently, there has been little evidence for more
      than one gene encoding each of the two major spidroin silk proteins, MaSp1 and
      MaSp2. Here, we report the deduced N-terminal domain sequences for two distinct
      MaSp1 genes from Nephila clavipes (MaSp1A and MaSp1B) and for MaSp2. All three
      MaSp genes are co-expressed in the major ampullate gland. A search of the GenBank
      database also revealed two distinct MaSp1 C-terminal domain sequences. Sequencing
      confirmed that both MaSp1 genes are present in all seven Nephila clavipes spiders
      examined. The presence of nucleotide polymorphisms in these genes confirmed that
      MaSp1A and MaSp1B are distinct genetic loci and not merely alleles of the same
      gene. We experimentally determined the transcription start sites for all three
      MaSp genes and established preliminary pairing between the two MaSp1 N- and C
      terminal domains. Phylogenetic analysis of these new sequences and other
      published MaSp N- and C-terminal domain sequences illustrated that duplications
      of MaSp genes may be widespread among spider species.

PMID- 18828838
TI  - Effects of classical insect hormones on the expression profiles of a lipase gene
      from the cotton bollworm (Helicoverpa armigera).
AB  - A 967-bp cDNA, encoding a 31 kDa lipase with an isoelectric point of 8.8, was
      cloned from Helicoverpa armigera. The gene was named Ha-lipase. The Ha-lipase
      transcript was present in the head-thorax, midgut and fat body but not in
      integument and haemocytes from 5th instar larvae, with higher expression levels
      in feeding larvae than that in molting larvae. In the midgut, transcription of
      the gene during the 5th instar larval period was lower than during the 6th instar
      period. While in the fat body, lipase was not found at the 6th instar stage but
      only at the 5th instar stage. The expression of Ha-lipase could be up-regulated
      by methoprene and down-regulated by methoxyfenozide (RH-2485) and 20
      hydroxyecdysone (20E).

PMID- 18828839
TI  - Characterization of the Drosophila melanogaster retinin gene encoding a cornea
      specific protein.
AB  - Two-dimensional analysis of head extracts from Drosophila melanogaster identified
      the four eye-specific protein spots corresponding to the retinin protein. The
      retinin protein spots were specifically stained with phosphoprotein-specific dye,
      suggesting that the retinin protein undergoes post-translational modification by
      phosphorylation. Northern blot analysis showed that the retinin gene begins to be
      expressed during the late stage of puparium formation during development.
      Analysis of the N-terminal sequence and expression of the retinin gene in S2
      suggest that retinin is a secretory protein. Transgenic flies with knockdown
      expression of the retinin gene by RNA interference (RNAi) were established.
      However, no significant phenotypic changes in eye structure or phototransduction
      were observed in the transgenic flies. Western blot analysis and
      immunohistochemical studies of D. melanogaster eyes suggest that retinin is a
      cornea-specific protein.

PMID- 18828840
TI  - Gene structure and expression of nanos (nos) and oskar (osk) orthologues of the
      vector mosquito, Culex quinquefasciatus.
AB  - The products of the maternal-effect genes, nanos (nos) and oskar (osk), are
      important for the development of germ cells in insects. Furthermore, these genes
      have been proposed as candidates for donating functional DNA regulatory sequences
      for use in gene drive systems to control transmission of mosquito-borne
      pathogens. The nos and osk genes of the cosmopolitan vector mosquito, Culex
      quinquefasciatus, encode proteins with domains common to orthologues found in
      other mosquitoes. Expression analyses support the conclusion that the role of
      these genes is conserved generally among members of the nematocera. Hybridization
      in situ analyses reveal differences in mRNA distribution in early embryos in
      comparison with the cyclorraphan, Drosophila melanogaster, highlighting a
      possible feature in the divergence of the clades each insect represents.

PMID- 18828841
TI  - Environmental conditions impinge on dragline silk protein composition.
AB  - The silk formed in the major ampullate (MA) gland of the orb weaving spider
      Nephila clavipes is composed of two silk fibroins, which are called major
      ampullate spidroins 1 (MaSp1) and 2 (MaSp2). Analysis of proteolytic peptides and
      reactivity to spidroin type specific antibodies indicated that MaSp2 constituted
      only a minor part in the spinning dope as well as in the spun filaments. Upon
      starvation, a change in the silk's characteristic features was observed that was
      concomitant of a decrease in the contribution of MaSp2. The silk became less
      elastic and stiffer, which will better tailor its usability for the safety line,
      albeit at the expense of its employment as the web frame threads. In addition,
      since MaSp2 production requires greater ATP consumption, such a shift in the
      protein ratio cuts down on the energy costs to produce the silk. From this change
      in protein composition the spider might therefore benefit twice, by synthesizing
      'cheaper' silk that into the bargain has properties that potentially can better
      support foraging in times of food shortage.

PMID- 18828842
TI  - Rapid cold hardening elicits changes in brain protein profiles of the flesh fly,
      Sarcophaga crassipalpis.
AB  - Rapid cold hardening (RCH) refers to the enhanced cold tolerance acquired by a
      brief exposure to a moderately low temperature. Although ecological aspects of
      this response have been well documented in insects, less is known about the
      physiological and biochemical mechanisms elicited by RCH. In this study we used
      two-dimensional electrophoresis to detect differences in brain protein abundance
      in pharate adults of the flesh fly Sarcophaga crassipalpis, in response to a 2 h
      RCH exposure at 0 degrees C. Fourteen high abundance proteins that responded to
      RCH were selected for mass spectrometric identification. Three proteins that
      increased in abundance during RCH included ATP synthase subunit alpha, a small
      heat shock protein (smHsp), and tropomyosin-1 isoforms 33/34. Eleven proteins
      that decreased in abundance or were missing following RCH included several
      proteins involved in energy metabolism, protein degradation, transcription, actin
      binding, and cytoskeleton organization. That several proteins increased in
      abundance during RCH underscores the dynamics of the RCH mechanism and suggests
      that more than one physiological response likely contribute to RCH. The increase
      in ATP synthase suggests an elevation of ATP during RCH, and the smHsp increase
      suggests that at least one of the Hsps is actually mobilized during RCH, rather
      than after RCH as previously assumed.

PMID- 18828843
TI  - A chitin deacetylase and putative insect intestinal lipases are components of the
      Mamestra configurata (Lepidoptera: Noctuidae) peritrophic matrix.
AB  - One- and two-dimensional gel electrophoresis coupled with liquid chromatography
      tandem mass spectrometry (LC-MS/MS) was used to identify cDNA encoding a chitin
      deacetylase (McCDA1) and three insect intestinal lipases (McIIL1, McIIL2 and
      McIIL3) associated with the Mamestra configurata (bertha armyworm) peritrophic
      matrix. Recombinant McCDA1 was active and chitin deacetylase activities were
      detected in the midgut. McCDA1 and the McIIL genes were expressed exclusively in
      the midgut; however, McCDA1 and McIIL2 were expressed in all larval stages,
      whereas McIIL1 was expressed mainly in feeding larvae and McIIL3 primarily during
      the moult.

PMID- 18828844
TI  - Molecular identification and characterization of two new Lepidoptera
      chemoreceptors belonging to the Drosophila melanogaster OR83b family.
AB  - In insect antennae, olfaction depends on olfactory receptors (ORs) that function
      through heterodimerization with an unusually highly conserved partner orthologue
      to the Drosophila melanogaster DOR83b. Here, we report the identification of two
      cDNAs encoding new DOR83b orthologues that represent the first members, although
      nonconventional, of the OR families of two noctuid crop pests, the cotton
      leafworm Spodoptera littoralis and the cabbage armyworm Mamestra brassicae. They
      both displayed high protein sequence conservation with previously identified
      DOR83b orthologues. Transcripts were abundantly detected in adult chemosensory
      organs as well as in fifth instar larvae heads. In adult antennae, the expression
      patterns of both genes revealed common features with other members of the OR83b
      subfamily: they appeared to be expressed at the bases of numerous olfactory
      sensilla belonging to different functional categories, suggesting that both
      receptors may be co-expressed with yet unidentified conventional ORs.
      Bioinformatic analyses predicted the occurrence of seven transmembrane domains
      and an unusual topology with intracellular N-termini and extracellular C-termini,
      extending to Lepidoptera the hypothesis of an inverted topology for DOR83b
      orthologues, demonstrated to date only in D. melanogaster.

PMID- 18828845
TI  - Vascular type of Ehlers-Danlos syndrome associated with mild haemophilia A.

PMID- 18828846
TI  - A rare repigmentation pattern in a vitiligo patient: a clue to an epidermal stem
      cell reservoir of melanocytes?

PMID- 18828847
TI  - High levels of fusidic acid-resistant Staphylococcus aureus despite restrictions
      on antibiotic use.
AB  - BACKGROUND: High rates of fusidic acid (FA)-resistant Staphylococcus aureus
      (FRSA) in patients with skin disease have been previously attributed to high
      usage of topical FA. AIMS: To assess whether local community guidelines to
      restrict topical FA has affected its prescription and use and the level of FRSA
      in patients with skin disease. METHODS: Stapylococcus aureus isolates from
      microbiology samples received over a 4-month period in 2004 were tested for
      antibiotic sensitivities. Comparison was then made with the results of a previous
      study carried out in 2001. RESULTS: A significant fall was seen in the use of
      topical FA in dermatology patients. In 2001, 62% of patients had used FA
      containing preparations within the previous 6 months, compared with just 15% of
      patients in 2004 (P < 0.001). The number of topical FA prescriptions in primary
      and secondary care dropped between 2001 and 2004. The proportion of S. aureus
      isolates resistant to FA in dermatology patients had not significantly fallen
      between 2001 (50%) and 2004 (41%) (P = 0.4). However, there was a significant
      increase in FA resistance within hospital inpatients, nondermatology outpatients
      and primary-care patients (P < 0.05). The FRSA level had doubled in hospital
      inpatients (20%) and almost tripled in nondermatology outpatients (28%) and
      primary care patients (25%). CONCLUSION: Persistent high levels of FA resistance
      may represent the development of an FRSA reservoir in the community. Continued
      restriction of FA is still recommended.

PMID- 18828848
TI  - A systematic review of randomized controlled trials of treatments for inherited
      forms of epidermolysis bullosa.
AB  - BACKGROUND: Many interventions have been described for inherited epidermolysis
      bullosa (EB), but it is unclear which are beneficial. AIMS: A systematic review
      of randomized controlled trials (RCTs) was performed to inform practice and
      highlight research gaps. METHODS: The Cochrane Central Register of Controlled
      Trials, MEDLINE, EMBASE and the Cochrane Skin Group specialist library, from
      inception until 1 April 2007, were searched. Primary outcomes were healing of
      lesions or prevention of new lesions. Trials were assessed for quality of
      reporting and data were extracted. RESULTS: Five randomized double-blind placebo
      controlled crossover studies were identified (n = 102). Two studies assessed oral
      tetracyclines in EB simplex (EBS). In one study (n = 12), 4/6 patients improved
      and 2/6 deteriorated on a dose of 1500 mg of tetracycline daily; only two
      patients completed the study. In the second study (n = 21), 6/18 and 7/18
      improved on oxytetracycline 1 g and placebo, respectively. Two RCTs assessed
      topical interventions for EBS: aluminium chloride hexahydrate solution 20% (n =
      23) and bufexamac cream 5% (n = 8). Neither showed a benefit over placebo. One
      RCT of 36 patients with recessive dystrophic EB compared phenytoin with placebo
      and failed to show any difference in mean lesion counts (difference = 0, 95% CI 
      11 to 4). CONCLUSIONS: There is no reliable trial evidence for interventions in
      inherited EB. In future, it may be that gene treatment becomes the best treatment
      approach for these diseases.

PMID- 18828849
TI  - All EU hands to the EU pumps: the Science Academies of Europe (EASAC) recommend
      strong support of research to tackle antibacterial resistance.
AB  - Despite many European Union (EU) conferences on fighting microbial resistance,
      rates of resistance in Europe continue to increase. Although research is catching
      up with discovery, the development of new antimicrobials is threatened by
      economic factors, in particular the need for a return of investment via high
      volume sales. The EU should invest in independent research into the economic and
      business aspects of antibiotic development. Multidisciplinary input from the
      fields of finance, law, marketing, sociology and psychology will inform a broad
      agenda for change at the regulatory, academic and commercial levels and identify
      new options for novel anti-infective research and development, as recently
      recommended by the Science Academies of Europe (EASAC).

PMID- 18828850
TI  - Performance indicators and the public reporting of healthcare-associated
      infection rates.
AB  - Surveillance of healthcare-associated infections (HCAIs) makes evident the
      importance of the quality of patient care, and the increasing demand for public
      reporting of HCAI surveillance data and related quality indicators is thus not
      surprising. However, there is little evidence that public reporting results in
      improved patient care. Debate continues about which HCAI-related indicators are
      the best measures of performance and thus the most appropriate for public
      reporting. Suitable indicators should allow improvements leading to better
      patient outcomes, and should be comparable among hospitals and countries.
      Appropriate examples include central vascular catheter infections, surgical
      prophylaxis and surgical site infections.

PMID- 18828851
TI  - Healthcare-associated infections: think globally, act locally.
AB  - Healthcare-associated infections (HAIs) have been a hot topic for several
      decades. An understanding of HAIs should be based on an understanding of the
      organisms that cause infection and determine prevention. Although some
      improvements in control in hospitals have been recorded, the community setting is
      now implicated, and the role of microbiology in diagnosis, detection of carriers
      and strain typing of organisms is evident. As healthcare systems vary widely,
      prevention strategies must be designed accordingly. Hand hygiene, however,
      remains applicable in all settings, and the WHO is strongly promoting alcohol
      based hand rubs to interrupt transmission. Some countries are only beginning to
      develop standards, whereas compliance is obligatory in others. Economics and cost
      factors are common to all countries, and litigation is increasingly a factor in
      some.

PMID- 18828852
TI  - Then and now: use of 16S rDNA gene sequencing for bacterial identification and
      discovery of novel bacteria in clinical microbiology laboratories.
AB  - In the last decade, as a result of the widespread use of PCR and DNA sequencing,
      16S rDNA sequencing has played a pivotal role in the accurate identification of
      bacterial isolates and the discovery of novel bacteria in clinical microbiology
      laboratories. For bacterial identification, 16S rDNA sequencing is particularly
      important in the case of bacteria with unusual phenotypic profiles, rare
      bacteria, slow-growing bacteria, uncultivable bacteria and culture-negative
      infections. Not only has it provided insights into aetiologies of infectious
      disease, but it also helps clinicians in choosing antibiotics and in determining
      the duration of treatment and infection control procedures. With the use of 16S
      rDNA sequencing, 215 novel bacterial species, 29 of which belong to novel genera,
      have been discovered from human specimens in the past 7 years of the 21st century
      (2001-2007). One hundred of the 215 novel species, 15 belonging to novel genera,
      have been found in four or more subjects. The largest number of novel species
      discovered were of the genera Mycobacterium (n = 12) and Nocardia (n = 6). The
      oral cavity/dental-related specimens (n = 19) and the gastrointestinal tract (n =
      26) were the most important sites for discovery and/or reservoirs of novel
      species. Among the 100 novel species, Streptococcus sinensis, Laribacter
      hongkongensis, Clostridium hathewayi and Borrelia spielmanii have been most
      thoroughly characterized, with the reservoirs and routes of transmission
      documented, and S. sinensis, L. hongkongensis and C. hathewayi have been found
      globally. One of the greatest hurdles in putting 16S rDNA sequencing into routine
      use in clinical microbiology laboratories is automation of the technology. The
      only step that can be automated at the moment is input of the 16S rDNA sequence
      of the bacterial isolate for identification into one of the software packages
      that will generate the result of the identity of the isolate on the basis of its
      sequence database. However, studies on the accuracy of the software packages have
      given highly varied results, and interpretation of results remains difficult for
      most technicians, and even for clinical microbiologists. To fully utilize 16S
      rDNA sequencing in clinical microbiology, better guidelines are needed for
      interpretation of the identification results, and additional/supplementary
      methods are necessary for bacterial species that cannot be identified confidently
      by 16S rDNA sequencing alone.

PMID- 18828853
TI  - Phenotypic and genotypic characterization of Neisseria gonorrhoeae in parts of
      Italy: detection of a multiresistant cluster circulating in a heterosexual
      network.
AB  - Data concerning Neisseria gonorrhoeae infections in Italy are scarce, and there
      is little information on the phenotypic and genotypic characteristics of the
      circulating strains. In this study, 326 isolates collected from 397 patients,
      with or without concurrent human immunodeficiency virus (HIV) infection, were
      cultured and characterized by serovar and antimicrobial susceptibility to five
      antimicrobials. N. gonorrhoeae multi-antigen sequence typing (NG-MAST) was also
      performed for strain characterization and to identify a transmission network.
      Gonococcal infection was diagnosed in 364 males and 33 females, 296 of whom were
      Italian and 96 of whom were foreigners (nationality was unknown in five cases).
      Among the 364 males, 197 were heterosexual, and the median age was 31 years.
      Approximately 8.3% of all the investigated patients were HIV-1-positive. The
      isolates were assigned to three different serovars (IA, IB, IA/IB), IB being the
      most frequently encountered. A significant rate of resistant gonococci was also
      observed; 34%, 25.5% and 19.1% of ciprofloxacin-resistant, penicillin-resistant
      and tetracycline-resistant phenotypes, respectively, were detected, and 10.2% of
      strains were multidrug-resistant. Together with the presence of different
      sequence types (STs), identified by NG-MAST, a multidrug-resistant cluster,
      ST661, was detected in a heterosexual network in a precise geographical area of
      the country. In particular, all strains belonging to ST661 showed identical
      profiles according to pulsed-field gel electrophoresis (PFGE), all were serotype
      IB, and all were resistant to penicillin, ciprofloxacin and tetracycline.

PMID- 18828854
TI  - Adherence and invasion of Bacteroidales isolated from the human intestinal tract.
AB  - Members of the genera Bacteroides and Parabacteroides are important constituents
      of both human and animal intestinal microbiota, and are significant facultative
      pathogens. In this study, the ability of Bacteroides spp. and Parabacteroides
      distasonis isolated from both diarrhoeal and normal stools (n = 114) to adhere to
      and invade HEp-2 cells was evaluated. The presence of putative virulence factors
      such as capsule and fimbriae was also investigated. Adherence to HEp-2 cells was
      observed in 75.4% of the strains, which displayed non-localized clusters.
      Invasion was observed in 37.5% and 26% of the strains isolated from diarrhoeal
      and non-diarrhoeal stools, respectively. All strains displayed a capsule, whereas
      none of them showed fimbriae-like structures. This is the first report of the
      ability of Bacteroides spp. and P. distasonis to adhere to and invade cultured
      HEp-2 epithelial cells.

PMID- 18828855
TI  - Usefulness of mec-associated direct repeat unit (dru) typing in the
      epidemiological analysis of highly clonal methicillin-resistant Staphylococcus
      aureus in Scotland.
AB  - The incidence of the epidemic methicillin-resistant Staphylococcus aureus (EMRSA)
      strains EMRSA-15 and EMRSA-16 in Scotland has increased dramatically, now
      accounting for c. 70% and c. 20% of isolates, respectively. Epidemiological
      tracking of these EMRSA strains is difficult, as c. 50% of EMRSA-15 and c. 35% of
      EMRSA-16 isolates are indistinguishable using pulsed-field gel electrophoresis
      (PFGE) and other typing methods. The usefulness of mec-associated direct repeat
      unit (dru) sequence analysis as a more sensitive approach to tracking the
      persistence and spread of these 'clonal' EMRSA strains in Scotland was evaluated.
      Analysis of 47 EMRSA-15 and 57 EMRSA-16 isolates (including two separately
      cultured isolates of the Harmony collection type strain) obtained from 22
      hospital laboratories over an 8-year period (1997-2005) revealed 13 and 12
      different dru types, respectively. Whereas some types appeared to be endemic in
      multiple hospitals, subtypes that may represent specific strain movement among
      hospitals in a given geographical region were identified in other instances.
      These results suggest that mec-associated dru typing may have potential for
      identifying and tracking specific subtypes of otherwise indistinguishable
      epidemic MRSA isolates such as those in Scotland.

PMID- 18828856
TI  - Evaluation of a new meropenem-EDTA double-ended Etest strip for the detection of
      the cfiA metallo-beta-lactamase gene in clinical isolates of Bacteroides
      fragilis.
AB  - Thirty-five Bacteroides fragilis clinical isolates with varying susceptibility to
      meropenem were analysed with a prototype of a double-ended Etest strip containing
      meropenem +/- EDTA, designed for the detection of the CfiA metallo-beta
      lactamase. Phenotypic results obtained with this new Etest strip were related to
      the genotype and compared to the results of the Etest containing imipenem +/-
      EDTA. Whereas the Etest with imipenem +/- EDTA only allowed detection of isolates
      with high-level resistance (both MICs of imipenem and meropenem >32 mg/L),
      reflecting the possible underestimation of CfiA prevalence in B. fragilis, the
      Etest with meropenem +/- EDTA proved to be more accurate, particularly for
      isolates with low-level carbapenem resistance, suggesting its potential for
      broader detection of CfiA production.

PMID- 18828857
TI  - Molecular epidemiology of carbapenem-resistant Acinetobacter baumannii in New
      Caledonia.
AB  - Carbapenem-resistant Acinetobacter baumannii (CR-Ab) ranked third, with a
      frequency of 24.8%, among 202 strains of multidrug-resistant bacteria isolated
      from clinical samples in the main hospital of New Caledonia in 2004. All CR-Ab
      isolates were analysed by isoelectric focusing, conjugation, pulsed-field gel
      electrophoresis and PCR for the presence of carbapenemase genes. Fifty CR-Ab
      isolates produced carbapenemase OXA-23. The isolates belonged to a single clone
      presenting several subtypes, suggesting an endemic situation. This study further
      illustrates the widespread prevalence of carbapenemase OXA-23-producing CR-Ab
      isolates in the South Pacific.

PMID- 18828858
TI  - EUCAST Technical Note on the method for the determination of broth dilution
      minimum inhibitory concentrations of antifungal agents for conidia-forming
      moulds.

PMID- 18828859
TI  - EUCAST Technical Note on voriconazole.

PMID- 18828860
TI  - Polymorphisms in eggshell organic matrix genes are associated with eggshell
      quality measurements in pedigree Rhode Island Red hens.
AB  - Novel and traditional eggshell quality measurements were made from up to 2000
      commercial pedigree hens for a candidate gene association analysis with organic
      eggshell matrix genes: ovocleidin-116, osteopontin (SPP1), ovocalyxin-32
      (RARRES1), ovotransferrin (LTF), ovalbumin and ovocalyxin-36, as well as key
      genes in the maintenance and function of the shell gland [estrogen receptor
      (ESR1) and carbonic anhydrase II (CAII)]. Associations were found for (i)
      ovalbumin with breaking strength and shell thickness; (ii) ovocleidin-116 with
      elastic modulus, shell thickness and egg shape; (iii) RARRES1 with mammillary
      layer thickness; (iv) ESR1 with dynamic stiffness; (v) SPP1 with fracture
      toughness and (vi) CAII with egg shape. The marker effects are as large as 17% of
      trait standard deviations and could be used to improve eggshell quality.

PMID- 18828861
TI  - SNP discovery in Litopenaeus vannamei with a new computational pipeline.
AB  - Litopenaeus vannamei (Pacific white shrimp) have been farmed in the Americas for
      many years and are growing in popularity in Asia with the development of specific
      pathogen-free stocks. The full genomic sequence of this species might not be
      available in the near future, so other tools are needed to discover the location
      of polymorphic sites for quantitative trait loci mapping, association studies and
      subsequent marker-assisted selection. Currently, 25 937 L. vannamei expressed
      sequence tags (ESTs) are publicly available. These sequences were manually
      screened, masked for tandem repeats and inputted into CAP3 for clustering. The
      resulting 3532 contigs were analysed for possible single nucleotide polymorphisms
      (SNPs) with SNPIDENTIFIER, a newly developed computer program for predicting
      SNPs. SNPIDENTIFIER is designed for ESTs without accompanying chromatogram
      sequence quality information, and therefore it performs quality control checks on
      all data. SNPIDENTIFIER sets a threshold such that the sequences used have a poor
      quality nucleotide (N) frequency <0.1, and it trims off the first 10 bases of
      every sequence to ensure higher sequence quality. For a base to be predicted as
      an SNP, the minor nucleotide (allele) frequency must be >0.1, it must be observed
      at least four times and the 15 bases on either side must exactly match the
      consensus sequence. Using these conservative parameters, 504 SNPs were predicted
      from 141 contigs for L. vannamei. A small sample of 18 individuals from three
      lines have been sequenced to verify prediction results and 17 of 39 (44%) of the
      tested SNPs have been confirmed.

PMID- 18828862
TI  - Characterization of expressed sequence tags from turkey skeletal muscle.
AB  - This study was designed to identify important muscle gene homologues in the
      turkey. Three skeletal muscle cDNA libraries representing distinct muscle
      developmental stages were constructed. A total of 20,042 clones were sequenced
      resulting in 13,023 finished high-quality sequences (trimmed, quality scored and
      masked) for analysis. Sequence clustering produced 1113 contigs and 4144
      singletons (5257 putative transcripts). Sequences were compared by blastn to the
      chicken whole-genome sequence and to the Ensembl and NCBI databases to identify
      homologous sequences. These surveys indicated that most of the important muscle
      genes are included in the sequence collection. Examination of contigs identified
      1288 single nucleotide polymorphisms and in 320 of those the minor allele was
      observed to be present in more than one sequence. This resource provides sequence
      variants for numerous genes in the turkey, as demonstrated by the SNP haplotypes
      that were constructed for 10 genes. Sequences obtained in this study provide the
      basis for constructing a skeletal muscle-focused microarray, a tool that will
      facilitate the analysis of genes expressed during turkey muscle development, as
      well as the expression of genes underlying the genetic basis of muscle
      characteristics associated with meat quality.

PMID- 18828863
TI  - A combined AFLP and microsatellite linkage map and pilot comparative genomic
      analysis of European sea bass Dicentrarchus labrax L.
AB  - European sea bass (Dicentrarchus labrax L., Moronidae, Teleostei) sustains a
      regional fishery and is commonly farmed in the Mediterranean basin, but has not
      undergone much long-term genetic improvement. An updated genetic linkage map of
      the European sea bass was constructed using 190 microsatellites, 176 amplified
      fragment length polymorphisms and two single nucleotide polymorphisms. From the
      45 new microsatellite markers (including 31 type I markers) reported in this
      study, 28 were mapped. A total of 368 markers were assembled into 35 linkage
      groups. Among these markers, 28 represented type I (coding) markers, including
      those located within the peptide Y, SOX10, PXN1, ERA and TCRB genes (linkage
      groups 1, 7, 16, 17 and 27 respectively). The sex-averaged map spanned 1373.1
      centimorgans (cM) of the genome. The female map measured 1380.0 cM, whereas the
      male map measured 1046.9 cM, leading to a female-to-male (F:M) recombination rate
      ratio of 1.32:1. The intermarker spacing of the second-generation linkage map of
      the European sea bass was 3.67 cM, which is smaller than that of the first
      generation linkage map (5.03 cM). Comparative mapping of microsatellite flanking
      regions was performed with five model teleosts and this revealed a high
      percentage (33.6%) of evolutionarily conserved regions with the three-spined
      stickleback.

PMID- 18828864
TI  - Managing childhood disability: progress in the past two decades.

PMID- 18828865
TI  - Altered lipoprotein metabolism in chronic inflammatory states: proinflammatory
      high-density lipoprotein and accelerated atherosclerosis in systemic lupus
      erythematosus and rheumatoid arthritis.
AB  - In this review, the authors discuss the formation and structure of high-density
      lipoproteins (HDLs) and how those particles are altered in inflammatory or stress
      states to lose their capacity for reverse cholesterol transport and for
      antioxidant activity. In addition, abnormal HDLs can become proinflammatory
      (piHDLs) and actually contribute to oxidative damage. The assay by which piHDLs
      are identified involves studying the ability of test HDLs to prevent oxidation of
      low-density lipoproteins. Finally, the authors discuss the potential role of
      piHDLs (found in some 45% of patients with systemic lupus erythematosus and 20%
      of patients with rheumatoid arthritis) in the accelerated atherosclerosis
      associated with some chronic rheumatic diseases.

PMID- 18828866
TI  - Regulation of cancer stem cells by p53.
AB  - The hypothesis that cancer stem cells are responsible for the chemoresistant and
      metastatic phenotypes of many breast cancers has gained support using cell
      sorting strategies to enrich the tumor-initiating population of cells. The
      mechanisms regulating the cancer stem cell pool, however, are less clear. Two
      recent publications suggest that loss of p53 permits expansion of presumptive
      cancer stem cells in mouse mammary tumors and in human breast cell lines. These
      results add restriction of cancer stem cells as a new tumor suppressor activity
      attributed to p53.

PMID- 18828867
TI  - A gene signature of loss of oestrogen receptor (ER) function and oxidative stress
      links ER-positive breast tumours with an absent progesterone receptor and a poor
      prognosis.
AB  - Prognostic gene signatures like the wound and hypoxia signature differ by
      assumptions of cellular growth. Although gene signatures show little overlap,
      they also track within the group of luminal breast tumours those with a high
      proliferation and poor prognosis. Oxidative stress is another assumption of
      cellular growth. It affects several pathological conditions through its influence
      on the regulation of protein kinases and signal transduction pathways. A
      comprehensive set of 62 core genes from cultured oestrogen- and oestrogen
      receptor-deprived epithelial breast cancer cells is responsive to three forms of
      oxidative stress. Evidence is presented that oxidative stress involves the
      development of an aggressive subset of primary oestrogen receptor-positive breast
      tumours.

PMID- 18828868
TI  - Pro/con debate: is the scoop and run approach the best approach to trauma
      services organization?
AB  - You are asked to be involved in organizing a trauma service for a major urban
      center. You are asked to make a decision on whether the services general approach
      to trauma in the city (which does have a well-established trauma center) will be
      scoop and run (minimal resuscitation at the scene with a goal to getting the
      patient to a trauma center as quickly as possible) or on-the-scene resuscitation
      with transfer following some degree of stabilization.

PMID- 18828869
TI  - Myocardial protection in sepsis.
AB  - Sepsis with myocardial dysfunction is seen commonly. Beta-blockers have been used
      successfully to treat chronic heart failure based on the premise that chronically
      elevated adrenergic drive is detrimental to the myocardium. However, recent
      reports on the acute use of beta-blockers in situations with potential
      hemodynamic compromise have shown the risks associated with this approach. In
      critical situations, the main effect of adrenergic activation is to support
      cardiovascular function. Caution should be exercised in designing studies to
      assess beta-blockers in septic patients.

PMID- 18828870
TI  - Bench-to-bedside review: the initial hemodynamic resuscitation of the septic
      patient according to Surviving Sepsis Campaign guidelines--does one size fit all?
AB  - The Surviving Sepsis Campaign guidelines for the management of severe sepsis and
      septic shock recommend that the initial hemodynamic resuscitation be done
      according to the protocol used by Rivers and colleagues in their well-known early
      goal-directed therapy (EGDT) study. However, it may well be that their patients
      were much sicker on admission than many other septic patients. Compared with
      other populations of septic patients, the patients of Rivers and colleagues had a
      higher incidence of severe comorbidities, a more severe hemodynamic status on
      admission (excessively low central venous oxygen saturation [ScvO2], low central
      venous pressure [CVP], and high lactate), and higher mortality rates. Therefore,
      it may well be that these patients arrived to the hospital in late untreated
      hypovolemic sepsis, which may have been due, in part at least, to low
      socioeconomic status and reduced access to health care. The EGDT protocol uses
      target values for CVP and ScvO2 to guide hemodynamic management. However, filling
      pressures do not reliably predict the response to fluid administration, while the
      ScvO2 of septic patients is characteristically high due to decreased oxygen
      extraction. For all these reasons, it seems that the hemodynamic component of the
      Surviving Sepsis Campaign guidelines cannot be applied to all septic patients,
      particularly those who develop sepsis during their hospital stay.

PMID- 18828871
TI  - Regression modelling in hospital epidemiology: a statistical note.

PMID- 18828872
TI  - Crops in all shapes and sizes.
AB  - A report of the joint American Society of Plant Biologists/Sociedad Mexicana De
      Bioquimica meeting held in Merida, Mexico, 26 June-1 July 2008.

PMID- 18828873
TI  - Bench-to-bedside review: adenosine receptors--promising targets in acute lung
      injury?
AB  - Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are life
      threatening disorders that have substantial adverse effects on outcomes in
      critically ill patients. ALI/ARDS develops in response to pulmonary or
      extrapulmonary injury and is characterized by increased leakage from the
      pulmonary microvasculature and excessive infiltration of polymorphonuclear cells
      into the lung. Currently, no therapeutic strategies are available to control
      these fundamental pathophysiological processes in human ALI/ARDS. In a variety of
      animal models and experimental settings, the purine nucleoside adenosine has been
      demonstrated to regulate both endothelial barrier integrity and polymorphonuclear
      cell trafficking in the lung. Adenosine exerts its effects through four G-protein
      coupled receptors (A1, A2A, A2B, and A3) that are expressed on leukocytes and
      nonhematopoietic cells, including endothelial and epithelial cells. Each type of
      adenosine receptor (AR) is characterized by a unique pharmacological and
      physiological profile. The development of selective AR agonists and antagonists,
      as well as the generation of gene-deficient mice, has contributed to a growing
      understanding of the cellular and molecular processes that are critically
      involved in the development of ALI/ARDS. Adenosine-dependent pathways are
      involved in both protective and proinflammatory effects, highlighting the need
      for a detailed characterization of the distinct pathways. This review summarizes
      current experimental observations on the role of adenosine signaling in the
      development of acute lung injury and illustrates that adenosine and ARs are
      promising targets that may be exploited in the development of innovative
      therapeutic strategies.

PMID- 18828875
TI  - Unlocking the power of cross-species genomic analyses: identification of
      evolutionarily conserved breast cancer networks and validation of preclinical
      models.
AB  - The application of high-throughput genomic technologies has revealed that
      individual breast tumors display a variety of molecular features that require
      more personalized approaches to treatment. Several recent studies have
      demonstrated that a cross-species analytic approach provides a powerful means to
      filter through genetic complexity by identifying evolutionarily conserved genetic
      networks that are fundamental to the oncogenic process. Mouse-human tumor
      comparisons will provide insights into cellular origins of tumor subtypes, define
      interactive oncogenetic networks, identify potential novel therapeutic targets,
      and further validate as well as guide the selection of genetically engineered
      mouse models for preclinical testing.

PMID- 18828876
TI  - Appetite for reproduction: dietary restriction, aging and the mammalian gonad.
AB  - The major physiologic theory of aging, the disposable soma theory, links dietary
      restriction (DR), also known as calorie or food restriction, to prolonged
      lifespan and makes specific predictions about the effects of aging and DR on
      reproduction. A recent study in BMC Biology profiling the effects of aging and DR
      on gonadal gene expression provides novel molecular evidence that has a
      significant impact on this theory of aging.

PMID- 18828877
TI  - Transcriptional (dys)regulation and aging in Caenorhabditis elegans.
AB  - A circuit of transcription factors has been discovered in Caenorhabditis elegans
      that could provide a link between laboratory-defined intracellular 'longevity
      pathways', gene dysregulation and the process of normal aging.

PMID- 18828878
TI  - Genetic studies in osteoporosis--the end of the beginning.
AB  - Osteoporosis and disorders of bone fragility are highly heritable, but despite
      much effort the identities of few of the genes involved has been established.
      Recent developments in genetics such as genome-wide association studies are
      revolutionizing research in this field, and it is likely that further
      contributions will be made through application of next-generation sequencing
      technologies, analysis of copy number variation polymorphisms, and high
      throughput mouse mutagenesis programs. This article outlines what we know about
      osteoporosis genetics to date and the probable future directions of research in
      this field.

PMID- 18828879
TI  - Breast cancer stem cell markers - the rocky road to clinical applications.
AB  - Lately, understanding the role of cancer stem cells in tumor initiation and
      progression became a major focus in stem cell biology and in cancer research.
      Considerable efforts, such as the recent studies by Honeth and colleagues,
      published in the June issue of Breast Cancer Research, are directed towards
      developing clinical applications of the cancer stem cell concepts. This work
      shows that the previously described CD44+CD24- stem cell phenotype is associated
      with basal-type breast cancers in human patients, in particular BRCA1 inherited
      cancers, but does not correlate with clinical outcome. These very interesting
      findings caution that the success of our efforts in translating cancer stem cell
      research into clinical practice depends on how thorough and rigorous we are at
      characterizing these cells.

PMID- 18828881
TI  - Transcriptome content and dynamics at single-nucleotide resolution.
AB  - Massively parallel short-tag sequencing of cDNA libraries--RNAseq--is being used
      to study the dynamics and complexity of eukaryotic transcriptomes, giving new
      biological insights into the 'active genome'.

PMID- 18828880
TI  - The telosome/shelterin complex and its functions.
AB  - The telomeres that cap the ends of eukaryotic chromosomes serve a dual role in
      protecting the chromosome ends and in intracellular signaling for regulating cell
      proliferation. A complex of six telomere-associated proteins has been identified-
      the telosome or shelterin complex--that is crucial for both the maintenance of
      telomere structure and its signaling functions.

PMID- 18828882
TI  - New insights into tumor suppressors.
AB  - A report of the Cold Spring Harbor Laboratory meeting 'Mechanisms and Models of
      Cancer', Cold Spring Harbor, USA, 13-17 August 2008.

PMID- 18828883
TI  - Virally associated arthritis 2008: clinical, epidemiologic, and pathophysiologic
      considerations.
AB  - Several viruses have been associated with the development of inflammatory
      arthritis, including the hepatitis viruses (hepatitis B virus and hepatitis C
      virus), HIV, the parvovirus B19, the human T-cell lymphotropic virus-I, and the
      alphaviruses. Here, we review the epidemiology, the pathophysiological
      mechanisms, the pertinent clinical and laboratory findings as well as the
      principles of therapy of the most common virus-associated arthritides. We believe
      that the knowledge of these key diagnostic and therapeutic features of virus
      associated arthritides is important for the rheumatologist of the 21st century.

PMID- 18828884
TI  - Circuit lifespan during continuous renal replacement therapy: children and adults
      are not equal.
AB  - In the field of continuous renal replacement therapy (CRRT), session length,
      downtime and dose require detailed research, which will provide information
      important in relation to prescription, anticoagulation and circuit material
      choice (membrane type and size, vascular access site and size). In particular, it
      appears that many of the data currently existing in the literature and accepted
      regarding CRRT prescription and delivery in critically ill adult patients are not
      strictly applicable to the paediatric setting. Furthermore, many of the available
      paediatric studies are small, retrospective or underpowered. In paediatric CRRT,
      epidemiological investigations and prospective trials to investigate practical
      aspects of extracorporeal therapies are welcome and urgently needed.

PMID- 18828885
TI  - Anticoagulant therapy in acute lung injury: a useful tool without proper
      operating instruction?
AB  - Activation of the coagulation cascade resulting in alveolar fibrin deposition is
      recognized as a hallmark of acute lung injury (ALI). Anticoagulant treatment with
      recombinant human activated protein C (rhAPC) appears promising, because - like
      in sepsis - there is a deficiency of protein C in ALI, which is correlated with
      poor outcome in both syndromes. Recently in Critical Care, Waerhaug and
      colleagues confirmed the beneficial effects of rhAPC on pulmonary function in
      ovine endotoxin-induced ALI. Notably, the authors reported no differences in
      hemorrhage in histologic analyses between rhAPC-treated and untreated animals.
      However, a recently reported randomized, placebo-controlled, multicenter trial in
      ALI patients without severe sepsis failed to identify any differences in the
      number of ventilator-free days or 60 day-mortality between the rhAPC and placebo
      group. In addition to (or perhaps because of) the complex pathogenesis, the
      discrepancy between clinical and experimental results in ALI is another common
      feature with sepsis. The future challenge will be to transfer our theoretical
      knowledge adequately into daily clinical practice. Anticoagulant therapy might be
      a useful tool in the treatment of ALI; however the proper operating instruction
      remains to be defined.

PMID- 18828886
TI  - Lipooxygenase inhibition in osteoarthritis: a potential symptomatic and disease
      modifying effect?
AB  - 5-Loxin is a compound extracted from an ancient herb that might be considered as
      a potent lipooxygenase inhibitor. The results observed in a preliminary trial
      suggest a highly intriguing clinically relevant symptomatic effect contrasting
      with a poor bioavailability of this compound. Moreover, in this trial, a
      statistically significant decrease in matrix metalloproteinase enzyme serum level
      suggests that, in addition to the observed symptomatic effect, such a compound
      might have a disease modifying effect in osteoarthritis. Further studies are
      required both to confirm the symptomatic efficacy and acceptable safety profile
      and to evaluate the potential chondromodulating effect of this compound.

PMID- 18828887
TI  - An important step towards completing the rheumatoid arthritis cycle.
AB  - In the previous issue of Arthritis Research & Therapy data are presented showing
      that circulating immune complexes containing citrullinated fibrin(ogen) are
      present in anti-citrullinated protein antibody-positive rheumatoid arthritis
      patients, and that such immune complexes co-localize with complement factor C3 in
      the rheumatoid synovium. These results corroborate the idea that citrullination
      is intimately involved in the pathophysiology of rheumatoid arthritis and
      complete our model (the rheumatoid arthritis cycle) for the development and
      chronic nature of this disease.

PMID- 18828888
TI  - Are biologics more effective than classical disease-modifying antirheumatic
      drugs?
AB  - Major achievements have been reached in the treatment of rheumatoid arthritis
      during past decades due to the recognition of methotrexate as an anchor drug for
      treatment of rheumatoid arthritis, due to the notion of a treatment window of
      opportunity in patients with recent-onset rheumatoid arthritis necessitating
      early aggressive therapy, due to the development of biologics and due to
      remission as a treatment target. Most biologics have a much faster onset of
      action than synthetic disease-modifying anti-rheumatic drugs, but presently there
      is no convincing evidence that biologic drugs have a superior clinical efficacy
      in comparison with the synthetic drugs. Biologics are, however, accompanied by
      less radiological deterioration.

PMID- 18828890
TI  - Will he still look good with the lights on? Spectral tuning of visual pigments in
      fish.
AB  - Visual perception is a key element in evolution, as it is required for many life
      processes. Two recent studies in BMC Biology and BMC Evolutionary Biology shed
      light on the genetic determinants of color detection in strikingly colored fish.

PMID- 18828891
TI  - Gastrointestinal dysfunction in the critically ill: can we measure it?
AB  - Gastrointestinal dysfunction is an intuitively important, yet descriptively
      elusive component of the multiple organ dysfunction syndrome. Reintam and
      colleagues have attempted to quantify this dimension using a combination of
      intolerance of enteral feeding, and the development of intra-abdominal
      hypertension. While they show that both parameters are associated with an
      increased risk of death (and therefore that, in combination, the risk of death is
      even greater), they fall short in developing a novel descriptor of
      gastrointestinal dysfunction. Nonetheless, and even with its shortcomings, their
      effort is a welcome contribution to the surprisingly complex process of
      describing the morbidity of critical illness.

PMID- 18828892
TI  - Flexible Two-Phase studies for rare exposures: Feasibility, planning and
      efficiency issues of a new variant.
AB  - The two-phase design consists of an initial (Phase One) study with known disease
      status and inexpensive covariate information. Within this initial study one
      selects a subsample on which to collect detailed covariate data. Two-phase
      studies have been shown to be efficient compared to standard case-control
      designs. However, potential problems arise if one cannot assure minimum sample
      sizes in the rarest categories or if recontact of subjects is difficult. In the
      case of a rare exposure with an inexpensive proxy, the authors propose the
      flexible two-phase design for which there is a single time of contact, at which a
      decision about full covariate ascertainment is made based on the proxy. Subjects
      are screened until the desired numbers of cases and controls have been selected
      for full data collection. Strategies for optimizing the cost/efficiency of this
      design and corresponding software are presented. The design is applied to two
      examples from occupational and genetic epidemiology. By ensuring minimum numbers
      for the rarest disease-covariate combination(s), we obtain considerable
      efficiency gains over standard two-phase studies with an improved practical
      feasibility. The flexible two-phase design may be the design of choice in the
      case of well targeted studies of the effect of rare exposures with an inexpensive
      proxy.

PMID- 18828894
TI  - BibGlimpse: the case for a light-weight reprint manager in distributed literature
      research.
AB  - BACKGROUND: While text-mining and distributed annotation systems both aim at
      capturing knowledge and presenting it in a standardized form, there have been few
      attempts to investigate potential synergies between these two fields. For
      instance, distributed annotation would be very well suited for providing topic
      focussed, expert knowledge enriched text corpora. A key limitation for this
      approach is the availability of literature annotation systems that can be
      routinely used by groups of collaborating researchers on a day to day basis, not
      distracting from the main focus of their work. RESULTS: For this purpose, we have
      designed BibGlimpse. Features like drop-to-file, SVM based automated retrieval of
      PubMed bibliography for PDF reprints, and annotation support make BibGlimpse an
      efficient, light-weight reprint manager that facilitates distributed literature
      research for work groups. Building on an established open search engine, full
      text search and structured queries are supported, while at the same time making
      shared collections of annotated reprints accessible to literature classification
      and text-mining tools. CONCLUSION: BibGlimpse offers scientists a tool that
      enhances their own literature management. Moreover, it may be used to create
      content enriched, annotated text corpora for research in text-mining.

PMID- 18828893
TI  - Heterologous expression of plasmodial proteins for structural studies and
      functional annotation.
AB  - Malaria remains the world's most devastating tropical infectious disease with as
      many as 40% of the world population living in risk areas. The widespread
      resistance of Plasmodium parasites to the cost-effective chloroquine and
      antifolates has forced the introduction of more costly drug combinations, such as
      Coartem. In the absence of a vaccine in the foreseeable future, one strategy to
      address the growing malaria problem is to identify and characterize new and
      durable antimalarial drug targets, the majority of which are parasite proteins.
      Biochemical and structure-activity analysis of these proteins is ultimately
      essential in the characterization of such targets but requires large amounts of
      functional protein. Even though heterologous protein production has now become a
      relatively routine endeavour for most proteins of diverse origins, the functional
      expression of soluble plasmodial proteins is highly problematic and slows the
      progress of antimalarial drug target discovery. Here the status quo of
      heterologous production of plasmodial proteins is presented, constraints are
      highlighted and alternative strategies and hosts for functional expression and
      annotation of plasmodial proteins are reviewed.

PMID- 18828895
TI  - Network evaluation from the consistency of the graph structure with the measured
      data.
AB  - BACKGROUND: A knowledge-based network, which is constructed by extracting as many
      relationships identified by experimental studies as possible and then
      superimposing them, is one of the promising approaches to investigate the
      associations between biological molecules. However, the molecular relationships
      change dynamically, depending on the conditions in a living cell, which suggests
      implicitly that all of the relationships in the knowledge-based network do not
      always exist. Here, we propose a novel method to estimate the consistency of a
      given network with the measured data: i) the network is quantified into a log
      likelihood from the measured data, based on the Gaussian network, and ii) the
      probability of the likelihood corresponding to the measured data, named the graph
      consistency probability (GCP), is estimated based on the generalized extreme
      value distribution. RESULTS: The plausibility and the performance of the present
      procedure are illustrated by various graphs with simulated data, and with two
      types of actual gene regulatory networks in Escherichia coli: the SOS DNA repair
      system with the corresponding data measured by fluorescence, and a set of 29
      networks with data measured under anaerobic conditions by microarray. In the
      simulation study, the procedure for estimating GCP is illustrated by a simple
      network, and the robustness of the method is scrutinized in terms of various
      aspects: dimensions of sampling data, parameters in the simulation study,
      magnitudes of data noise, and variations of network structures. In the actual
      networks, the former example revealed that our method operates well for an actual
      network with a size similar to those of the simulated networks, and the latter
      example illustrated that our method can select the activated network candidates
      consistent with the actual data measured under specific conditions, among the
      many network candidates. CONCLUSION: The present method shows the possibility of
      bridging between the static network from the literature and the corresponding
      measurements, and thus will shed light on the network structure variations in
      terms of the changes in molecular interaction mechanisms that occur in response
      to the environment in a living cell.

PMID- 18828896
TI  - Role of cervical dendritic cell subsets, co-stimulatory molecules, cytokine
      secretion profile and beta-estradiol in development of sequalae to Chlamydia
      trachomatis infection.
AB  - BACKGROUND: Chlamydia trachomatis infection of the female genital tract can lead
      to serious sequelae resulting in fertility related disorders. Little is known
      about the mechanism leading to Chlamydia induced pathology and factors
      responsible for it. As only some of the women develops reproductive disorders
      while majority of the women clears infection without any severe sequalae, mucosal
      immune response in women with or without fertility disorders was studied to
      identify factors which may lead to final clinical outcome of chlamydial
      infection. METHODS: Myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) populations in
      cervical mucosa and peripheral blood were analyzed in controls and Chlamydia
      positive women with or without fertility disorders with multicoloured flow
      cytometric analysis. Cervical cytokines (IL-6, IL-8, IL-10, IL-12, TNF-alpha and
      IFN-gamma), C-reactive protein levels and sex hormone levels in serum were
      quantified by ELISA. RESULTS: In cervix of Chlamydia positive women with
      fertility disorders, significantly high (P < 0.05) numbers of pDCs were present
      with increased CD80 expression. pDCs correlated significantly with C-reactive
      protein levels, IL-6 and IFN-gamma levels in women with fertility disorders. In
      contrast, mDCs showed significant upregulation of CD1a during chlamydial
      infection and correlated significantly with IL-12 levels in Chlamydia positive
      fertile women. beta-estradiol levels were significantly higher in women having
      fertility disorders as compared to fertile women and have significant
      correlations (r = 0.65; P < 0.05) with pDCs numbers, CD80 expression, IL-6 levels
      and IFN-gamma levels in these women. CONCLUSION: These results suggest that
      development of sequalae in some women can be a result of interplay of many
      factors including type of dendritic cell, co stimulatory molecule expression,
      cytokine secretion pattern and hormone levels.

PMID- 18828897
TI  - Comparative phosphoproteomics reveals evolutionary and functional conservation of
      phosphorylation across eukaryotes.
AB  - BACKGROUND: Reversible phosphorylation of proteins is involved in a wide range of
      processes, ranging from signaling cascades to regulation of protein complex
      assembly. Little is known about the structure and evolution of phosphorylation
      networks. Recent high-throughput phosphoproteomics studies have resulted in the
      rapid accumulation of phosphopeptide datasets for many model organisms. Here, we
      exploit these novel data for the comparative analysis of phosphorylation events
      between different species of eukaryotes. RESULTS: Comparison of phosphoproteomics
      datasets of six eukaryotes yields an overlap ranging from approximately 700 sites
      for human and mouse (two large datasets of closely related species) to a single
      site for fish and yeast (distantly related as well as two of the smallest
      datasets). Some conserved events appear surprisingly old; those shared by plant
      and animals suggest conservation over the time scale of a billion years. In spite
      of the hypothesized incomprehensive nature of phosphoproteomics datasets and
      differences in experimental procedures, we show that the overlap between
      phosphoproteomes is greater than expected by chance and indicates increased
      functional relevance. Despite the dynamic nature of the evolution of
      phosphorylation, the relative overlap between the different datasets is identical
      to the phylogeny of the species studied. CONCLUSION: This analysis provides a
      framework for the generation of biological insights by comparative analysis of
      high-throughput phosphoproteomics datasets. We expect the rapidly growing body of
      data from high-throughput mass spectrometry analysis to make comparative
      phosphoproteomics a powerful tool for elucidating the evolutionary and functional
      dynamics of reversible phosphorylation.

PMID- 18828898
TI  - Physical activity referrals in Swedish primary health care - prescriber and
      patient characteristics, reasons for prescriptions, and prescribed activities.
AB  - BACKGROUND: Over the past decade, practitioners in primary health care (PHC)
      settings in many countries have issued written prescriptions to patients to
      promote increased physical activity or exercise. The aim of this study is to
      describe and analyse a comprehensive physical activity referral (PAR) scheme
      implemented in a routine PHC setting in Ostergotland County. The study examines
      characteristics of the PARs recipients and referral practitioners, identifies
      reasons why practitioners opted to use PARs with their clients, and discusses
      prescribed activities and prescriptions in relation to PHC registries. METHODS:
      Prospective prescription data were obtained for 90% of the primary health care
      centres in Ostergotland County, Sweden, in 2004 and 2005. The study population
      consisted of patients who were issued PARs after they were deemed likely to
      benefit from increased physical activity, as assessed by PHC staff. RESULTS:
      During the two-year period, a total of 6,300 patients received PARs. Two-thirds
      of the patients were female and half of the patients were 45-64 years. Half of
      the patients (50.8%) who received PARs were recommended a home-based activity,
      such as walking. One third (33%) of the patients issued PARs were totally
      inactive, reporting no days of physical activity that lasted for 30 minutes, and
      29% stated that they reached this level 1-2 days per week. The number of PARs
      prescribed per year in relation to the number of unique individuals that visited
      primary health care during one year was 1.4% in 2004 and 1.2% in 2005. Two-thirds
      of the combined prescriptions were issued by physicians (38%) and nurses (31%).
      Physiotherapists and behavioural scientists issued the highest relative number of
      prescriptions. The most common reasons for issuing PARs were musculoskeletal
      disorders (39.1%) and overweight (35.4%), followed by high blood pressure (23.3%)
      and diabetes (23.2%). CONCLUSION: Ostergotland County's PAR scheme reached a
      relatively high proportion of physically inactive people visiting local PHC
      centres for other health reasons. PAR-related statistics, including PAR-rates by
      individual PHC centres and PAR- rates per health professional category, show
      differences in prescribing activities, both by patient categories, and by
      prescribing professionals.

PMID- 18828899
TI  - Therapeutic and prophylactic effect of intermittent preventive anti-malarial
      treatment in infants (IPTi) from Ghana and Gabon.
AB  - BACKGROUND: Intermittent preventive treatment in infants (IPTi) with sulphadoxine
      pyrimethamine (SP) reduces the incidence of malaria episodes in young children.
      The exact mechanism by which the protective effect is mediated needs to be
      defined. This study aimed to investigate therapeutic, prophylactic, and possible
      exceeding effects of SP-based IPTi in two clinical trials. METHODS: Protective
      efficacies from two IPTi trials performed in Kumasi, Ghana, and Lambarene, Gabon,
      were assessed for overlapping time series of 61 days. For six-months periods
      after each of three IPTi doses a multivariate Poisson regression model with the
      respective cohort as co-variate was generated and effect modification of
      protective efficacy with time strata was evaluated by log-likelihood tests.
      RESULTS: Protective efficacies were not significantly different between the two
      study cohorts. Study-cohort corrected protective efficacy was highest for the
      first 61 days after each IPTi application and decreased continuously. For the
      first 61 days after IPTi-1, IPTi-2, and IPTi-3 the protective efficacy was 71%,
      44%, and 43%, respectively. A reduction of the malaria incidence rate was
      detectable for the first 60, 30 and 40 days after IPTi-1, IPTi-2 and IPTi-3 drug
      application, respectively. After IPTi-3 a higher risk for malaria could be seen
      after day 60. This effect was mainly based on the overwhelming influence of the
      Kumasi cohort. CONCLUSION: The results suggest that SP-based IPTi mainly works
      through a therapeutic and prophylactic effect over 30 to 60 days after drug
      application and that a sustained effect beyond post-treatment prophylaxis might
      be very low. TRIAL REGISTRATION: Data analysis from clinical trials NCT ID #
      00206739 (Kumasi Trial) and NCT ID # 00167843 (Lambarene Trial),
      http://www.clinicaltrials.gov.

PMID- 18828901
TI  - Border malaria in China: knowledge and use of personal protection by minority
      populations and implications for malaria control: a questionnaire-based survey.
AB  - BACKGROUND: Malaria control in remote, forested areas of the Mekong region relies
      on personal protection from mosquito bites. Uptake of these methods may be
      limited by knowledge of the link between mosquitoes and malaria as well as social
      and economic aspects. Understanding barriers to uptake will inform malaria
      control programmes on targets for improvement of delivery. METHODS: A total 748
      key respondents: health providers and village heads, from 187 villages and 25
      different ethnic groups, were interviewed using structured questionnaires.
      Differences in use of personal protection, and knowledge of malaria between
      groups were analysed using chi-square; and binary logistic regression used for
      multivariate analysis. RESULTS: Malaria knowledge was poor with 19.4% of women
      and 37.5% of men linking mosquitoes with malaria, although 95.6% knew one or more
      methods of mosquito control. Virtually all respondents used personal protection
      at some time during the year; and understanding of malaria transmission was
      strongly associated with bednet use. Those working in forest agriculture were
      significantly more likely to know that mosquitoes transmit malaria but this did
      not translate into a significantly greater likelihood of using bednets.
      Furthermore, use of personal protection while woing outdoors was rare, and less
      than 3% of respondents knew about the insecticide impregnation of bednets. The
      use of bednets, synthetic repellents and mosquito coils varied between ethnic
      groups, but was significantly more frequent among those with higher income, more
      years of education and permanent housing. The reported use of repellents and
      coils was also more common among women despite their low knowledge of malaria
      transmission, and low likelihood of having heard information on malaria within
      the last year. CONCLUSION: The use of personal protection must be increased,
      particularly among outdoor workers that have higher malaria risk. However,
      personal protection is widely used and widely accepted to prevent nuisance biting
      mosquitoes, with the major barrier to use being affordability. Therefore, social
      marketing campaigns aimed at women and those that work outdoors that provide
      highly subsidised products, especially insecticide impregnation kits for bednets
      and hammock nets are most likely to succeed in lowering malaria morbidity among
      non Han-Chinese groups in rural China.

PMID- 18828900
TI  - MDM2 SNP309 is associated with high grade node positive breast tumours and is in
      linkage disequilibrium with a novel MDM2 intron 1 polymorphism.
AB  - INTRODUCTION: A functional polymorphism within MDM2, SNP309 T>G, has been linked
      to early onset cancer. This study examined clinical associations of breast cancer
      with SNP309 in a Scottish Caucasian population and investigated additional MDM2
      intron 1 polymorphisms. METHODS: Intron 1 of MDM2 was PCR amplified and directly
      sequenced from 299 breast cancer patients and 275 cancer free controls and
      compared with clinical and pathological parameters. RESULTS: SNP309 was observed,
      for the control and breast cancer cohorts respectively, at frequencies of: T/T =
      44.7% and 39.5%; G/T = 42.2% and 47.2%; G/G = 13.1% and 13.4%, indicating that
      SNP309 is not a predisposing factor for breast cancer. The 309G/G genotype was
      associated with high grade tumours (OR = 1.64, 95%CI = 1.06-2.53, p = 0.025) and
      greater nodal involvement (OR = 2.51, 95%CI = 1.26-4.98, p = 0.009). SNP309 was
      not associated with an earlier age of cancer diagnosis. No association was
      observed between genotype and age of breast cancer diagnosis when patients were
      stratified by menopausal status and estrogen receptor status. Three additional
      low frequency SNPs were identified: 344T>A, 285G>C and 443G>T, the latter two
      novel. SNP285 was in complete linkage disequilibrium with SNP309 (D' = 1.0) with
      the minor alleles being in phase with each other. Moreover, the 285C/C, 309G/G
      double homozygous genotype was only observed in the breast cancer cohort.
      CONCLUSION: SNP309G/G is associated with poor prognostic breast cancer features
      in the Scottish population. Additionally, a novel SNP, SNP285, that is in linkage
      disequilibrium with SNP309, may also have a role in breast tumorigenesis.

PMID- 18828902
TI  - Identification and characterization of domains responsible for self-assembly and
      cell wall binding of the surface layer protein of Lactobacillus brevis ATCC 8287.
AB  - BACKGROUND: Lactobacillus brevis ATCC 8287 is covered by a regular surface (S-)
      layer consisting of a 435 amino acid protein SlpA. This protein is completely
      unrelated in sequence to the previously characterized S-layer proteins of
      Lactobacillus acidophilus group. RESULTS: In this work, the self-assembly and
      cell wall binding domains of SlpA were characterized. The C-terminal self
      assembly domain encompassed residues 179-435 of mature SlpA, as demonstrated by
      the ability of N-terminally truncated recombinant SlpA to form a periodic
      structure indistinguishable from that formed by full length SlpA. Furthermore, a
      trypsin degradation analysis indicated the existence of a protease resistant C
      terminal domain of 214 amino acids. By producing a set of C-terminally truncated
      recombinant SlpA (rSlpA) proteins the cell wall binding region was mapped to the
      N-terminal part of SlpA, where the first 145 amino acids of mature SlpA alone
      were sufficient for binding to isolated cell wall fragments of L. brevis ATCC
      8287. The binding of full length rSlpA to the cell walls was not affected by the
      treatment of the walls with 5% trichloroacetic acid (TCA), indicating that cell
      wall structures other than teichoic acids are involved, a feature not shared by
      the Lactobacillus acidophilus group S-layer proteins characterized so far.
      Conserved carbohydrate binding motifs were identified in the positively charged N
      terminal regions of six Lactobacillus brevis S-layer proteins. CONCLUSION: This
      study identifies SlpA as a two-domain protein in which the order of the
      functional domains is reversed compared to other characterized Lactobacillus S
      layer proteins, and emphasizes the diversity of potential cell wall receptors
      despite similar carbohydrate binding sequence motifs in Lactobacillus S-layer
      proteins.

PMID- 18828903
TI  - A new method to determine tissue specific tissue factor thrombomodulin
      activities: endotoxin and particulate air pollution induced disbalance.
AB  - BACKGROUND: Increase in tissue factor (TF) and loss in thrombomodulin (TM)
      antigen levels has been described in various inflammatory disorders. The
      functional consequences of such changes in antigen concentrations in the
      coagulation balance are, however, not known. This study was designed to assess
      the consequences of inflammation-driven organ specific functional properties of
      the procoagulant response. METHODS: Tissue specific procoagulant activity was
      assessed by adding tissue homogenate to normal human pool plasma and recording of
      the thrombin generation curve. The new technique was subsequently applied on two
      inflammation driven animal models: 1) mouse lipopolysaccharide (LPS) induced
      endotoxemia and 2) spontaneously hypertensive rats exposed to environmental air
      pollution (particulate matter (PM). RESULTS: Addition of lung tissue from
      untreated animals to human plasma suppressed the endogenous thrombin potential
      (ETP) (175 +/- 61 vs. 1437 +/- 112 nM.min for control). This inhibitory effect
      was due to TM, because a) it was absent in protein C deficient plasma and b)
      lungs from TMpro/pro mice allowed full thrombin generation (ETP: 1686 +/- 209
      nM.min). The inhibitory effect of TM was lost after LPS administration to mice,
      which induced TF activity in lungs of C57Bl/6 mice as well as increased the ETP
      (941 +/- 523 vs. 194 +/- 159 nM.min for control). Another pro-inflammatory
      stimulus, PM dose-dependently increased TF in the lungs of spontaneously
      hypertensive rats at 4 and 48 hours after PM exposure. The ETP increased up to 48
      hours at the highest concentration of PM (1441 +/- 289 nM.min vs. saline: 164 +/-
      64 nM.min, p < 0.0001), suggesting a concentration- and time dependent reduction
      in TM activity. CONCLUSION: Inflammation associated procoagulant effects in
      tissues are dependent on variations in activity of the TF-TM balance. The
      application of these novel organ specific functional assays is a useful tool to
      monitor inflammation-driven shifts in the coagulation balance within animal or
      human tissues.

PMID- 18828905
TI  - Adenocarcinoma of the third portion of the duodenum in a man with CREST syndrome.
AB  - BACKGROUND: CREST (Calcinosis, Raynaud's phenomenon, Esophageal dysmotility,
      Sclerodactyly and Telangiectasias) syndrome has been rarely associated with other
      malignancies (lung, esophagus). This is the first report of a primary
      adenocarcinoma of the third portion of the duodenum in a patient with CREST
      syndrome. CASE PRESENTATION: A 54-year-old male patient with CREST syndrome
      presented with colicky postprandial pain of the upper abdomen, diminished food
      uptake and a 6-Kg-body weight loss during the previous 2 months. An ulcerative
      lesion in the third portion of the duodenum was revealed during duodenoscopy,
      with a diagnosis of adenocarcinoma on biopsy specimen histology. The patient
      underwent a partial pancreatoduodenectomy. No adjuvant therapy was instituted and
      follow-up is negative for local recurrence or metastases 21 months
      postoperatively. CONCLUSION: CREST syndrome has been associated with colon
      cancer, gastric polyps, familial adenomatous polyposis (FAP) syndrome and Crohn's
      disease; however, this is the first report of a primary adenocarcinoma of the
      duodenum in a patient with CREST syndrome. However, any etiologic relationship
      remains to be further investigated.

PMID- 18828904
TI  - Regulatory and structural properties differentiating the chromosomal and the
      bacteriophage-associated Escherichia coli O157:H7 Cu, Zn superoxide dismutases.
AB  - BACKGROUND: Highly virulent enterohemorrhagic Escherichia coli O157:H7 strains
      possess three sodC genes encoding for periplasmic Cu, Zn superoxide dismutases:
      sodC, which is identical to the gene present in non-pathogenic E. coli strains,
      and sodC-F1 and sodC-F2, two nearly identical genes located within lambdoid
      prophage sequences. The significance of this apparent sodC redundancy in E. coli
      O157:H7 has not yet been investigated. RESULTS: We report that strains deleted of
      one or more sodC genes are less resistant than the wild type strain to a
      challenge with hydrogen peroxide, thus confirming their involvement in the
      bacterial antioxidant apparatus. To understand if the different sodC genes have
      truly overlapping functions, we have carried out a comparison of the functional,
      structural and regulatory properties of the various E. coli O157:H7 SodC enzymes.
      We have found that the chromosomal and prophagic sodC genes are differentially
      regulated in vitro. sodC is exclusively expressed in aerobic cultures grown to
      the stationary phase. In contrast, sodC-F1 and sodC-F2 are expressed also in the
      logarithmic phase and in anaerobic cultures. Moreover, the abundance of SodC
      F1/SodC-F2 increases with respect to that of SodC in bacteria recovered from
      infected Caco-2 cells, suggesting higher expression/stability of SodC-F1/SodC-F2
      in intracellular environments. This observation correlates with the properties of
      the proteins. In fact, monomeric SodC and dimeric SodC-F1/SodC-F2 are
      characterized by sharp differences in catalytic activity, metal affinity,
      protease resistance and stability. CONCLUSION: Our data show that the chromosomal
      and bacteriophage-associated E. coli O157:H7 sodC genes have different regulatory
      properties and encode for proteins with distinct structural/functional features,
      suggesting that they likely play distinctive roles in bacterial protection from
      reactive oxygen species. In particular, dimeric SodC-F1 and SodC-F2 possess
      physico-chemical properties which make these enzymes more suitable than SodC to
      resist the harsh environmental conditions which are encountered by bacteria
      within the infected host.

PMID- 18828906
TI  - Optimizing care in osteoporosis: the Canadian quality circle project.
AB  - BACKGROUND: While the Osteoporosis Canada 2002 Canadian guidelines provided
      evidence based strategies in preventing, diagnosing, and managing this condition,
      publication and distribution of guidelines have not, in and of themselves, been
      shown to alter physicians clinical approaches. We hypothesize that primary care
      physicians enrolled in the Quality Circle project would change their patient
      management of osteoporosis in terms of awareness of osteoporosis risk factors and
      bone mineral density testing in accordance with the guidelines. METHODS: The
      project consisted of five Quality Circle phases that included: 1) Training &
      Baseline Data Collection, 2) First Educational Intervention & First Follow-Up
      Data Collection 3) First Strategy Implementation Session, 4) Final Educational
      Intervention & Final Follow-up Data Collection, and 5) Final Strategy
      Implementation Session. A total of 340 circle members formed 34 quality circles
      and participated in the study. The generalized estimating equations approach was
      used to model physician awareness of risk factors for osteoporosis and
      appropriate utilization of bone mineral density testing pre and post educational
      intervention (first year of the study). Odds ratios (OR) and 95% confidence
      intervals (95% CI) were calculated. RESULTS: After the 1st year of the study,
      physicians' certainty of their patients' risk factor status increased. Certainty
      varied from an OR of 1.4 (95% CI: 1.1, 1.8) for prior vertebral fracture status
      to 6.3 (95% CI: 2.3, 17.9) for prior hip fracture status. Furthermore, bone
      mineral density testing increased in high risk as compared with low risk patients
      (OR: 1.4; 95% CI: 1.2, 1.7). CONCLUSION: Quality Circle methodology was
      successful in increasing both physicians' awareness of osteoporosis risk factors
      and appropriate bone mineral density testing in accordance with the 2002 Canadian
      guidelines.

PMID- 18828907
TI  - Rapid identification of PAX2/5/8 direct downstream targets in the otic vesicle by
      combinatorial use of bioinformatics tools.
AB  - BACKGROUND: The pax2/5/8 genes belonging to the PAX family of transcription
      factors are key developmental regulators that are involved in the patterning of
      various embryonic tissues. More particularly, their function in inner ear
      specification has been widely described. However, little is known about the
      direct downstream targets and, so far, no global approaches have been performed
      to identify these target genes in this particular tissue. RESULTS: Here we
      present an original bioinformatics pipeline composed of comparative genomics,
      database querying and text mining tools, which is designed to rapidly and
      specifically discover PAX2/5/8 direct downstream targets involved in inner ear
      development. We provide evidence supported by experimental validation in medaka
      fish that brain 2 (POU domain, class 3, transcription factor 2), claudin-7,
      secretory pathway component sec31-like and meteorin-like precursor are novel
      direct downstream targets of PAX2/5/8. CONCLUSIONS: This study illustrates the
      power of extensive mining of public data repositories using bioinformatics
      methods to provide answers for a specific biological question. It furthermore
      demonstrates how the usage of such a combinatorial approach is advantageous for
      the biologist in terms of experimentation time and costs.

PMID- 18828908
TI  - Functional analysis of the novel TBX5 c.1333delC mutation resulting in an
      extended TBX5 protein.
AB  - BACKGROUND: Autosomal dominant Holt-Oram syndrome (HOS) is caused by mutations in
      the TBX5 gene and is characterized by congenital heart and preaxial radial ray
      upper limb defects. Most of the TBX5 mutations found in patients with HOS cause
      premature truncation of the primary TBX5 transcript. TBX5 missense mutations
      alter the three-dimensional structure of the protein and result in failed nuclear
      localization or reduced binding to target DNA. In this study we present our
      functional analyses of the novel and unusual c.1333delC mutation found in a
      patient with classical HOS. METHODS: The functional impact of this novel mutation
      was assessed by investigating the intracellular localization of the resulting
      TBX5 protein and its ability to activate the expression of its downstream target
      ANF. RESULTS: The deletion of the cytosine is the first TBX5 frameshift mutation
      predicted to result in an elongated TBX5 protein with 74 miscoding amino acids
      and 62 supernumerary C-terminal amino acids. The c.1333delC mutation affects
      neither the nuclear localization, nor its colocalization with SALL4, but severely
      affects the activation of the ANF promoter. CONCLUSION: The mutation c.1333delC
      does not locate within functional domains, but impairs the activation of the
      downstream target. This suggests that misfolding of the protein prevents its
      biological function.

PMID- 18828909
TI  - Characterization of mouse orofacial pain and the effects of lesioning TRPV1
      expressing neurons on operant behavior.
AB  - BACKGROUND: Rodent models of orofacial pain typically use methods adapted from
      manipulations to hind paw; however, limitations of these models include animal
      restraint and subjective assessments of behavior by the experimenter. In contrast
      to these methods, assessment of operant responses to painful stimuli has been
      shown to overcome these limitations and expand the breadth of interpretation of
      the behavioral responses. In the current study, we used an operant model based on
      a reward-conflict paradigm to assess nociceptive responses in three strains of
      mice (SKH1-Hrhr, C57BL/6J, TRPV1 knockout). We previously validated this operant
      model in rats and hypothesized in this study that wild-type mice would
      demonstrate a similar thermal stimulus-dependent response and similar operant
      pain behaviors. Additionally, we evaluated the effects on operant behaviors of
      mice manipulated genetically (e.g., TRPV1 k.o.) or pharmacologically with
      resiniferatoxin (RTX), a lesioning agent for TRPV1-expressing neurons. During the
      reward-conflict task, mice accessed a sweetened milk reward solution by
      voluntarily position their face against a neutral or heated thermode (37-55
      degrees C). RESULTS: As the temperature of the thermal stimulus became noxiously
      hot, reward licking events in SKH1-Hrhr and C57BL/6J mice declined while licking
      events in TRPV1 k.o. mice were insensitive to noxious heat within the activation
      range of TRPV1 (37-52 degrees C). All three strains displayed nocifensive
      behaviors at 55 degrees C, as indicated by a significant decrease in reward
      licking events. Induction of neurogenic inflammation by topical application of
      capsaicin reduced licking events in SKH1-Hrhr mice, and morphine rescued this
      response. Again, these results parallel what we previously documented using rats
      in this operant system. Following intracisternal treatment with RTX, C57BL/6J
      mice demonstrated a block of noxious heat at both 48 and 55 degrees C. RTX
      treated TRPV1 k.o. mice and all vehicle-treated mice displayed similar reward
      licking events as compared to the pre-treatment baseline levels. Both TRPV1 k.o.
      and RTX-treated C57BL/6J had complete abolishment of eye-wipe responses following
      corneal application of capsaicin. CONCLUSION: Taken together, these results
      indicate the benefits of using the operant test system to investigate pain
      sensitivity in mice. This ability provides an essential step in the development
      of new treatments for patients suffering from orofacial pain disorders.

PMID- 18828910
TI  - Identification and characterization of CCAAT/Enhancer Binding proteindelta
      (C/EBPdelta) target genes in G0 growth arrested mammary epithelial cells.
AB  - BACKGROUND: CCAAT/Enhancer Binding Proteindelta (C/EBPdelta) is a member of the
      highly conserved C/EBP family of leucine zipper (bZIP) proteins. C/EBPdelta is
      highly expressed in G0 growth arrested mammary epithelial cells (MECs) and "loss
      of function" alterations in C/EBPdelta have been associated with impaired contact
      inhibition, increased genomic instability and increased cell migration. Reduced
      C/EBPdelta expression has also been reported in breast cancer and acute myeloid
      leukemia (AML). C/EBPdelta functions as a transcriptional activator, however,
      only a limited number of C/EBPdelta target genes have been reported. As a result,
      the role of C/EBPdelta in growth control and the potential mechanisms by which
      "loss of function" alterations in C/EBPdelta contribute to tumorigenesis are
      poorly understood. The goals of the present study were to identify C/EBPdelta
      target genes using Chromatin Immunoprecipitation coupled with a CpG Island
      (HCG12K) Array gene chip ("ChIP-chip") assay and to assess the expression and
      potential functional roles of C/EBPdelta target genes in growth control. RESULTS:
      ChIP-chip assays identified approximately 100 C/EBPdelta target gene loci which
      were classified by gene ontology (GO) into cell adhesion, cell cycle regulation,
      apoptosis, signal transduction, intermediary metabolism, gene transcription, DNA
      repair and solute transport categories. Conventional ChIP assays validated the
      ChIP-chip results and demonstrated that 14/14 C/EBPdelta target loci were bound
      by C/EBPdelta in G0 growth arrested MCF-12A MECs. Gene-specific RT-PCR analysis
      also demonstrated C/EBPdelta-inducible expression of 14/14 C/EBPdelta target
      genes in G0 growth arrested MCF-12A MECs. Finally, expression of endogenous
      C/EBPdelta and selected C/EBPdelta target genes was also demonstrated in contact
      inhibited G0 growth arrested nontransformed human MCF-10A MECs and in mouse HC11
      MECs. The results demonstrate consistent activation and downstream function of
      C/EBPdelta in growth arrested human and murine MECs. CONCLUSION: C/EBPdelta
      target genes were identified by a global gene array approach and classified into
      functional categories that are consistent with biological contexts in which
      C/EBPdelta is induced, such as contact-mediated G0 growth arrest, apoptosis,
      metabolism and inflammation. The identification and validation of C/EBPdelta
      target genes provides new insights into the mechanistic role of C/EBPdelta in
      mammary epithelial cell biology and sheds new light on the potential impact of
      "loss of function" alterations in C/EBPdelta in tumorigenesis.

PMID- 18828912
TI  - The relationship between health-related quality of life and social networks among
      Japanese family caregivers for people with disabilities.
AB  - AIMS: The purpose of this study was to examine HRQOL depending on whether the
      participants have family members with disabilities or not. In addition, we
      examined the relationship between HRQOL and social networks among family
      caregivers in Japan. METHODS: The study has a cross-sectional design. Survey
      forms were distributed to 9205 people aged 30 and older who visited a dispensing
      pharmacy within fifteen areas of Japan. We collected data on gender, age, job
      status, and care giving status for persons with disabilities. Moreover, we
      assessed support size, social support, and HRQOL. Out of the 2029 questionnaires
      returned, 1763 (male: 663, female: 1100, mean age = 63.06 +/- 13.34) were valid
      for statistical analyses (the available response rate was 19.15%). RESULTS: A
      significant difference in HRQOL was identified between family caregivers and non
      family caregivers. Further, in males (N = 101), the results confirmed that only
      social support predicted the PCS and MCS scores, while other variables did not
      predict either score. On the other hand, in females (N = 144), it was found from
      the second step of hierarchical multiple regression analysis that only age
      explained the PCS score, while job status and support size explained the MCS
      score. CONCLUSION: It is reasonable to conclude that the HRQOL of family
      caregivers was lower than that of non-family caregivers, and that the HRQOL of
      family caregivers was estimated by their social networks.

PMID- 18828911
TI  - The conservation pattern of short linear motifs is highly correlated with the
      function of interacting protein domains.
AB  - BACKGROUND: Many well-represented domains recognize primary sequences usually
      less than 10 amino acids in length, called Short Linear Motifs (SLiMs). Accurate
      prediction of SLiMs has been difficult because they are short (often < 10 amino
      acids) and highly degenerate. In this study, we combined scoring matrixes derived
      from peptide library and conservation analysis to identify protein classes
      enriched of functional SLiMs recognized by SH2, SH3, PDZ and S/T kinase domains.
      RESULTS: Our combined approach revealed that SLiMs are highly conserved in
      proteins from functional classes that are known to interact with a specific
      domain, but that they are not conserved in most other protein groups. We found
      that SLiMs recognized by SH2 domains were highly conserved in receptor
      kinases/phosphatases, adaptor molecules, and tyrosine kinases/phosphatases, that
      SLiMs recognized by SH3 domains were highly conserved in cytoskeletal and
      cytoskeletal-associated proteins, that SLiMs recognized by PDZ domains were
      highly conserved in membrane proteins such as channels and receptors, and that
      SLiMs recognized by S/T kinase domains were highly conserved in adaptor
      molecules, S/T kinases/phosphatases, and proteins involved in transcription or
      cell cycle control. We studied Tyr-SLiMs recognized by SH2 domains in more
      detail, and found that SH2-recognized Tyr-SLiMs on the cytoplasmic side of
      membrane proteins are more highly conserved than those on the extra-cellular
      side. Also, we found that SH2-recognized Tyr-SLiMs that are associated with SH3
      motifs and a tyrosine kinase phosphorylation motif are more highly conserved.
      CONCLUSION: The interactome of protein domains is reflected by the evolutionary
      conservation of SLiMs recognized by these domains. Combining scoring matrixes
      derived from peptide libraries and conservation analysis, we would be able to
      find those protein groups that are more likely to interact with specific domains.

PMID- 18828914
TI  - Syndrome of arachnomelia in Simmental cattle.
AB  - BACKGROUND: The syndrome of arachnomelia is an inherited malformation mainly of
      limbs, back and head in cattle. At present the arachnomelia syndrome has been
      well known mainly in Brown Swiss cattle. Nevertheless, the arachnomelia syndrome
      had been observed in the Hessian Simmental population during the decade 1964
      1974. Recently, stillborn Simmental calves were observed having a morphology
      similar to the arachnomelia syndrome. The goal of this work was the
      characterization of the morphology and genealogy of the syndrome in Simmental to
      establish the basis for an effective management of the disease. RESULTS: The
      first pathologically confirmed arachnomelia syndrome-cases in the current
      Simmental population appeared in the year 2005. By 2007, an additional 140 calves
      with the arachnomelia syndrome were identified. The major pathological findings
      were malformed bones affecting the head, long bones of the legs and the vertebral
      column. It could be shown that, with the exception of two cases that were
      considered as phenocopies, all of the paternal and about two-third of the
      maternal pedigrees of the affected calves could be traced back to one common
      founder. Together with the data from experimental matings, the pedigree data
      support an autosomal recessive mutation being the etiology of the arachnomelia
      syndrome. The frequency of the mutation in the current population was estimated
      to be 3.32%. CONCLUSION: We describe the repeated occurrence of the arachnomelia
      syndrome in Simmental calves. It resembles completely the same defect occurring
      in the Brown Swiss breed. The mutation became relatively widespread amongst the
      current population. Therefore, a control system has to be established and it is
      highly desirable to map the disease and develop a genetic test system.

PMID- 18828913
TI  - P-loop mutations and novel therapeutic approaches for imatinib failures in
      chronic myeloid leukemia.
AB  - Imatinib was the first BCR-ABL-targeted agent approved for the treatment of
      patients with chronic myeloid leukemia (CML) and confers significant benefit for
      most patients; however, a substantial number of patients are either initially
      refractory or develop resistance. Point mutations within the ABL kinase domain of
      the BCR-ABL fusion protein are a major underlying cause of resistance. Of the
      known imatinib-resistant mutations, the most frequently occurring involve the ATP
      binding loop (P-loop). In vitro evidence has suggested that these mutations are
      more oncogenic with respect to other mutations and wild type BCR-ABL. Dasatinib
      and nilotinib have been approved for second-line treatment of patients with CML
      who demonstrate resistance (or intolerance) to imatinib. Both agents have marked
      activity in patients resistant to imatinib; however, they have differential
      activity against certain mutations, including those of the P-loop. Data from
      clinical trials suggest that dasatinib may be more effective vs. nilotinib for
      treating patients harboring P-loop mutations. Other mutations that are
      differentially sensitive to the second-line tyrosine kinase inhibitors (TKIs)
      include F317L and F359I/V, which are more sensitive to nilotinib and dasatinib,
      respectively. P-loop status in patients with CML and the potency of TKIs against
      P-loop mutations are key determinants for prognosis and response to treatment.
      This communication reviews the clinical importance of P-loop mutations and the
      efficacy of the currently available TKIs against them.

PMID- 18828916
TI  - Filarial granuloma of the testicular tunic mimicking a testicular neoplasm: a
      case report.
AB  - INTRODUCTION: Any firm or solid intratesticular mass on examination and/or any
      hypoechoic area within the tunica albuginea on imaging is markedly suspicious for
      testicular cancer. Filarial involvement of the testicular tunic has not been
      reported previously. CASE PRESENTATION: A 32-year-old man presented with a
      history of noticing a swelling in his right testicle for a period of 1 month
      which had become painful over the 10 days before presentation. Pre-operative
      imaging failed to shed light on the nature of the lesions (malignant or benign).
      The diagnostic dilemma was explained to the patient and informed consent was
      obtained for an orchiectomy. The patient underwent a high inguinal orchiectomy.
      The histopathology revealed a filarial granuloma of the testicular tunic.
      CONCLUSION: While it is generally regarded that any testicular swelling,
      especially in a young person, should be treated as a malignancy unless proven
      otherwise, it is important to remember that infectious diseases such as
      filariasis and tuberculosis may mimic neoplasms. Careful consideration of these
      diagnoses must be given when dealing with testicular swellings especially in
      areas where the prevalence of these diseases is high.

PMID- 18828915
TI  - A genome wide analysis of the response to uncapped telomeres in budding yeast
      reveals a novel role for the NAD+ biosynthetic gene BNA2 in chromosome end
      protection.
AB  - BACKGROUND: Telomeres prevent the ends of eukaryotic chromosomes from being
      recognized as damaged DNA and protect against cancer and ageing. When telomere
      structure is perturbed, a co-ordinated series of events promote arrest of the
      cell cycle so that cells carrying damaged telomeres do not divide. In order to
      better understand the eukaryotic response to telomere damage, budding yeast
      strains harboring a temperature sensitive allele of an essential telomere capping
      gene (cdc13-1) were subjected to a transcriptomic study. RESULTS: The genome-wide
      response to uncapped telomeres in yeast cdc13-1 strains, which have telomere
      capping defects at temperatures above approximately 27 degrees C, was determined.
      Telomere uncapping in cdc13-1 strains is associated with the differential
      expression of over 600 transcripts. Transcripts affecting responses to DNA damage
      and diverse environmental stresses were statistically over-represented. BNA2,
      required for the biosynthesis of NAD+, is highly and significantly up-regulated
      upon telomere uncapping in cdc13-1 strains. We find that deletion of BNA2 and
      NPT1, which is also involved in NAD+ synthesis, suppresses the temperature
      sensitivity of cdc13-1 strains, indicating that NAD+ metabolism may be linked to
      telomere end protection. CONCLUSIONS: Our data support the hypothesis that the
      response to telomere uncapping is related to, but distinct from, the response to
      non-telomeric double-strand breaks. The induction of environmental stress
      responses may be a conserved feature of the eukaryotic response to telomere
      damage. BNA2, which is involved in NAD+ synthesis, plays previously unidentified
      roles in the cellular response to telomere uncapping.

PMID- 18828917
TI  - Autoadjusting-CPAP effect on serum leptin concentrations in obstructive sleep
      apnoea patients.
AB  - BACKGROUND: Leptin is an hormone that regulates body weight. Studies have shown
      increasing leptin concentrations according to body mass index (BMI) and
      intermittent hypoxia. Our aim is to evaluate the basal leptin levels in OSA
      patients and its possible relation to OSA severity, independently of confounders
      and investigate the Autoadjusting-CPAP effect on leptin values. METHODS: In
      ninety eight male patients with moderate to severe OSA leptin serum levels were
      evaluated before therapy, 9 days and 6 months after therapy. RESULTS: In this
      group mean age was 55.3 years, mean BMI was 33.2 Kg/m2 and mean Apnoea- Hypopnea
      Index (AHI) was 51.7/h. Mean basal serum leptin value was 12.1 ug/L. Univariate
      analysis showed a significant correlation between serum leptin values and BMI (R
      = 0.68; p < 0.001), waist-hip ratio (R = 0.283; p = 0.004) and AHI (R = 0.198; p
      = 0.048); in stepwise multiple regression analysis only BMI (p < 0.001) was a
      predictor of serum leptin values. One week after therapy, mean leptin serum level
      decreased to 11.0 ug/L and 6 months after it was 11.4 ug/L. (p = 0.56 and p =
      0.387, respectively) CONCLUSION: Baseline leptin serum levels positively
      correlate with BMI, fat distributio and OSA severity. BMI is the only predictor
      of basal leptin levels.Treatment with Autoadjusting-CPAP has a small effect on
      leptin levels.

PMID- 18828918
TI  - Persistent spatial working memory deficits in rats with bilateral cortical
      microgyria.
AB  - BACKGROUND: Anomalies of cortical neuronal migration (e.g., microgyria (MG)
      and/or ectopias) are associated with a variety of language and cognitive deficits
      in human populations. In rodents, postnatal focal freezing lesions lead to the
      formation of cortical microgyria similar to those seen in human dyslexic brains,
      and also cause subsequent deficits in rapid auditory processing similar to those
      reported in human language impaired populations. Thus convergent findings support
      the ongoing study of disruptions in neuronal migration in rats as a putative
      model to provide insight on human language disability. Since deficits in working
      memory using both verbal and non-verbal tasks also characterize dyslexic
      populations, the present study examined the effects of neonatally induced
      bilateral cortical microgyria (MG) on working memory in adult male rats. METHODS:
      A delayed match-to-sample radial water maze task, in which the goal arm was
      altered among eight locations on a daily basis, was used to assess working memory
      performance in MG (n = 8) and sham (n = 10) littermates. RESULTS: Over a period
      of 60 sessions of testing (each session comprising one pre-delay sample trial,
      and one post-delay test trial), all rats showed learning as evidenced by a
      significant decrease in overall test errors. However, MG rats made significantly
      more errors than shams during initial testing, and this memory deficit was still
      evident after 60 days (12 weeks) of testing. Analyses performed on daily error
      patterns showed that over the course of testing, MG rats utilized a strategy
      similar to shams (but with less effectiveness, as indicated by more errors).
      CONCLUSION: These results indicate persistent abnormalities in the spatial
      working memory system in rats with induced disruptions of neocortical neuronal
      migration.

PMID- 18828919
TI  - Membrane diffusion- and capillary blood volume measurements are not useful as
      screening tools for pulmonary arterial hypertension in systemic sclerosis: a case
      control study.
AB  - BACKGROUND: There is no optimal screening tool for the assessment of pulmonary
      arterial hypertension (PAH) in patients with systemic sclerosis (SSc). A
      decreasing transfer factor of the lung for CO (TLCO) is associated with the
      development of PAH in SSc. TLCO can be partitioned into the diffusion of the
      alveolar capillary membrane (Dm) and the capillary blood volume (Vc). The use of
      the partitioned diffusion to detect PAH in SSc is not well established yet. This
      study evaluates whether Dm and Vc could be candidates for further study of the
      use for screening for PAH in SSc. METHODS: Eleven SSc patients with PAH
      (SScPAH+), 13 SSc patients without PAH (SScPAH-) and 10 healthy control subjects
      were included. Pulmonary function testing took place at diagnosis of PAH. TLCO
      was partitioned according to Roughton and Forster. As pulmonary fibrosis in SSc
      influences values of the (partitioned) TLCO, these were adjusted for fibrosis
      score as assessed on HRCT. RESULTS: TLCO as percentage of predicted (%) was lower
      in SScPAH+ than in SScPAH- (41 +/- 7% vs. 63 +/- 12%, p < 0.0001, respectively).
      Dm% in SScPAH+ was decreased as compared with SScPAH- (22 +/- 6% vs. 39 +/- 12%,
      p < 0.0001, respectively), also after adjustment for total fibrosis score (before
      adjustment: B = 17.5, 95% CI 9.0-25.9, p = < 0.0001; after adjustment: B = 14.3,
      95% CI 6.0-21.7, p = 0.008). No difference was found in Vc%. There were no
      correlations between pulmonary hemodynamic parameters and Dm% in the PAH groups.
      CONCLUSION: SScPAH+ patients have lower Dm% than SScPAH- patients. There are no
      correlations between Dm% and hemodynamic parameters of PAH in SScPAH+. These
      findings do not support further study of the role of partitioning TLCO in the
      diagnostic work- up for PAH in SSc.

PMID- 18828920
TI  - D- and L-lactate dehydrogenases during invertebrate evolution.
AB  - BACKGROUND: The L-lactate and D-lactate dehydrogenases, which are involved in the
      reduction of pyruvate to L(-)-lactate and D(+)-lactate, belong to evolutionarily
      unrelated enzyme families. The genes encoding L-LDH have been used as a model for
      gene duplication due to the multiple paralogs found in eubacteria,
      archaebacteria, and eukaryotes. Phylogenetic studies have suggested that several
      gene duplication events led to the main isozymes of this gene family in
      chordates, but little is known about the evolution of L-Ldh in invertebrates.
      While most invertebrates preferentially oxidize L-lactic acid, several species of
      mollusks, a few arthropods and polychaetes were found to have exclusively D-LDH
      enzymatic activity. Therefore, it has been suggested that L-LDH and D-LDH are
      mutually exclusive. However, recent characterization of putative mammalian D-LDH
      with significant similarity to yeast proteins showing D-LDH activity suggests
      that at least mammals have the two naturally occurring forms of LDH specific to L
      and D-lactate. This study describes the phylogenetic relationships of
      invertebrate L-LDH and D-LDH with special emphasis on crustaceans, and discusses
      gene duplication events during the evolution of L-Ldh. RESULTS: Our phylogenetic
      analyses of L-LDH in vertebrates are consistent with the general view that the
      main isozymes (LDH-A, LDH-B and LDH-C) evolved through a series of gene
      duplications after the vertebrates diverged from tunicates. We report several
      gene duplication events in the crustacean, Daphnia pulex, and the leech,
      Helobdella robusta. Several amino acid sequences with strong similarity to
      putative mammalian D-LDH and to yeast DLD1 with D-LDH activity were found in both
      vertebrates and invertebrates. CONCLUSION: The presence of both L-Ldh and D-Ldh
      genes in several chordates and invertebrates suggests that the two enzymatic
      forms are not necessarily mutually exclusive. Although, the evolution of L-Ldh
      has been punctuated by multiple events of gene duplication in both vertebrates
      and invertebrates, a shared evolutionary history of this gene in the two groups
      is apparent. Moreover, the high degree of sequence similarity among D-LDH amino
      acid sequences suggests that they share a common evolutionary history.

PMID- 18828921
TI  - The effects of the Mulligan Sustained Natural Apophyseal Glide (SNAG)
      mobilisation in the lumbar flexion range of asymptomatic subjects as measured by
      the Zebris CMS20 3-D motion analysis system.
AB  - BACKGROUND: Mulligan's mobilisation techniques are thought to increase the range
      of movement (ROM) in patients with low back pain. The primary aim of this study
      was to investigate the application of the Mulligan's Sustained Natural Apophyseal
      Glide (SNAG) technique on lumbar flexion ROM. The secondary aim was to measure
      the intra- and inter-day reliability of lumbar ROM employing the same procedure.
      METHODS: 49 asymptomatic volunteers participated in this double-blinded study.
      Subjects were randomly assigned to receive either SNAG mobilisation (n = 25), or
      a sham mobilisation (n = 24). The SNAG technique was applied at the L3and L4
      spinal levels with active flexion in sitting by an experienced manual therapist.
      Three sets of 10 repetitions at each of the two spinal levels were performed. The
      sham mobilisation was similar to the SNAG but did not apply the appropriate
      direction or force. Lumbar ROM was measured by a three dimensional electronic
      goniometer (Zebris CMS20), before and after each technique. For the reliability,
      five measurements in two different days (one week apart) were performed in 20
      healthy subjects. RESULTS: When both interventions were compared, independent t
      tests yielded no statistically significant results in ROM between groups (p =
      0.673). Furthermore no significant within group differences were observed: SNAG
      (p = 0.842), sham (p = 0.169). Intra- and inter-day reliability of flexion
      measurements was high (ICC(1,1) > 0.82, SEM < 4.0 degrees , SDD<16.3%) indicating
      acceptable clinical applicability. CONCLUSION: While the Zebris proved to be a
      reliable device for measuring lumbar flexion ROM, SNAG mobilisation did not
      demonstrate significant differences in flexion ROM when compared to sham
      mobilisation. TRIAL REGISTRATION: Current Controlled Trials NCT00678093.

PMID- 18828922
TI  - One-step refolding and purification of disulfide-containing proteins with a C
      terminal MESNA thioester.
AB  - BACKGROUND: Expression systems based on self-cleavable intein domains allow the
      generation of recombinant proteins with a C-terminal thioester. This uniquely
      reactive C-terminus can be used in native chemical ligation reactions to
      introduce synthetic groups or to immobilize proteins on surfaces and
      nanoparticles. Unfortunately, common refolding procedures for recombinant
      proteins that contain disulfide bonds do not preserve the thioester functionality
      and therefore novel refolding procedures need to be developed. RESULTS: A novel
      redox buffer consisting of MESNA and diMESNA showed a refolding efficiency
      comparable to that of GSH/GSSG and prevented loss of the protein's thioester
      functionality. Moreover, introduction of the MESNA/diMESNA redox couple in the
      cleavage buffer allowed simultaneous on-column refolding of Ribonuclease A and
      intein-mediated cleavage to yield Ribonuclease A with a C-terminal MESNA
      thioester. The C-terminal thioester was shown to be active in native chemical
      ligation. CONCLUSION: An efficient method was developed for the production of
      disulfide bond containing proteins with C-terminal thioesters. Introduction of a
      MESNA/diMESNA redox couple resulted in simultaneous on-column refolding,
      purification and thioester generation of the model protein Ribonuclease A.

PMID- 18828923
TI  - Capillary electrophoresis for the characterization of quantum dots after non
      selective or selective bioconjugation with antibodies for immunoassay.
AB  - Capillary electrophoresis coupled with laser-induced fluorescence was used for
      the characterization of quantum dots and their conjugates to biological
      molecules. The CE-LIF was laboratory-built and capable of injection (hydrodynamic
      and electrokinetic) from sample volumes as low as 4 muL via the use of a modified
      micro-fluidic chip platform. Commercially available quantum dots were
      bioconjugated to proteins and immunoglobulins through the use of established
      techniques (non-selective and selective). Non-selective techniques involved the
      use of EDCHCl/sulfo-NHS for the conjugation of BSA and myoglobin to carboxylic
      acid-functionalized quantum dots. Selective techniques involved 1) the use of
      heterobifunctional crosslinker, sulfo-SMCC, for the conjugation of partially
      reduced IgG to amine-functionalized quantum dots, and 2) the conjugation of
      periodate-oxidized IgGs to hydrazide-functionalized quantum dots. The migration
      times of these conjugates were determined in comparison to their non-conjugated
      QD relatives based upon their charge-to-size ratio values. The performance of
      capillary electrophoresis in characterizing immunoconjugates of quantum dot
      labeled IgGs was also evaluated. Together, both QDs and CE-LIF can be applied as
      a sensitive technique for the detection of biological molecules. This work will
      contribute to the advancements in applying nanotechnology for molecular diagnosis
      in medical field.

PMID- 18828924
TI  - Novel therapies in breast cancer: what is new from ASCO 2008.
AB  - INTRODUCTION: Breast cancer is the most common female cancer and the second most
      common cause of female cancer-related deaths in the United States. World-wide,
      more than one million women will be diagnosed with breast cancer annually. In
      2007, more than 175,000 women were diagnosed with breast cancer in the United
      States. However, deaths due to breast cancer have decreased in the recent years
      in part because of improved screening techniques, surgical interventions,
      understanding of the pathogenesis of the disease, and utilization of traditional
      chemotherapies in a more efficacious manner. One of the more exciting areas of
      improvement in the treatment of breast cancer is the entrance of novel therapies
      now available to oncologists. In the field of cancer therapeutics, the area of
      targeted and biologic therapies has been progressing at a rapid rate,
      particularly in the treatment of breast cancer.Since the advent of imatinib for
      the successful treatment of chronic myelogenous leukemia in the 2001, clinicians
      have been searching for comparable therapies that could be as efficacious and as
      tolerable. In order for targeted therapies to be effective, the agent must be
      able to inhibit critical regulatory pathways which promote tumor cell growth and
      proliferation. The targets must be identifiable, quantifiable and capable of
      being interrupted.In the field of breast cancer, two advances in targeted therapy
      have led to great strides in the understanding and treatment of breast cancer,
      namely hormonal therapy for estrogen positive receptor breast cancer and
      antibodies directed towards the inhibition of human epidermal growth factor
      receptor (HER)2. These advances have revolutionized the understanding and the
      treatment strategies for breast cancer. Building upon these successes, a host of
      novel agents are currently being investigated and used in clinical trials that
      will hopefully prove to be as fruitful. This review will focus on novel therapies
      in the field of breast cancer with a focus on metastatic breast cancer (MBC) and
      updates from the recent annual ASCO meeting and contains a summary of the
      results.

PMID- 18828926
TI  - Exercise training in the aerobic/anaerobic metabolic transition prevents glucose
      intolerance in alloxan-treated rats.
AB  - BACKGROUND: Ninety percent of cases of diabetes are of the slowly evolving non
      insulin-dependent type, or Type 2 diabetes. Lack of exercise is regarded as one
      of the main causes of this disorder. In this study we analyzed the effects of
      physical exercise on glucose homeostasis in adult rats with type 2 diabetes
      induced by a neonatal injection of alloxan. METHODS: Female Wistar rats aged 6
      days were injected with either 250 mg/kg of body weight of alloxan or citrate
      buffer 0.01 M (controls). After weaning, half of the animals in each group were
      subjected to physical training adjusted to meet the aerobic-anaerobic metabolic
      transition by swimming 1 h/day for 5 days a week with weight overloads. The
      necessary overload used was set and periodically readjusted for each rat through
      effort tests based on the maximal lactate steady state procedure. When aged 28,
      60, 90, and 120 days, the rats underwent glucose tolerance tests (GTT) and their
      peripheral insulin sensitivity was evaluated using the HOMA index. RESULTS: The
      area under the serum glucose curve obtained through GTT was always higher in
      alloxan-treated animals than in controls. A decrease in this area was observed in
      trained alloxan-treated rats at 90 and 120 days old compared with non-trained
      animals. At 90 days old the trained controls showed lower HOMA indices than the
      non-trained controls. CONCLUSION: Neonatal administration of alloxan induced a
      persistent glucose intolerance in all injected rats, which was successfully
      counteracted by physical training in the aerobic/anaerobic metabolic transition.

PMID- 18828925
TI  - Central cholinergic signal-mediated neuroendocrine regulation of vasopressin and
      oxytocin in ovine fetuses.
AB  - BACKGROUND: The hypothalamic-neurohypophysial system plays a fundamental role in
      the maintenance of body fluid homeostasis by secreting arginine vasopressin (AVP)
      and oxytocin (OT) in response to a variety of signals, including osmotic and
      nonosmotic stimuli. It is well established that central cholinergic mechanisms
      are critical in the regulation of cardiovascular responses and maintenance of
      body fluid homeostasis in adults. Our recent study demonstrated that
      intracerebroventricular (i.c.v.) injection of carbachol elicited an increase of
      blood pressure in the near-term ovine fetuses. However, in utero development of
      brain cholinergic mechanisms in the regulation of the hypothalamic neuropeptides
      is largely unknown. This study investigated AVP and OT neural activation in the
      fetal hypothalamus induced by central carbachol. RESULTS: Chronically prepared
      near-term ovine fetuses (0.9 gestation) received an i.c.v. carbachol (3
      microg/kg). Fetal blood samples were collected for AVP and OT assay, and brains
      were used for c-fos mapping studies. I.c.v. carbachol significantly increased
      fetal plasma AVP and OT concentrations. Intense FOS immunoreactivity (FOS-ir) was
      observed in the fetal supraoptic nuclei (SON) and paraventricular nuclei (PVN) in
      the hypothalamus. Double labeling demonstrated that a number of AVP- and OT
      containing neurons in the fetal SON and PVN were expressing c-fos in response to
      central carbachol. CONCLUSION: The results indicate that the central cholinergic
      mechanism is established and functional in the regulation of the hypothalamic
      neuropeptides during the final trimester of pregnancy. This provides evidence for
      a functional link between the development of central cholinergic mechanisms and
      hypothalamic neuropeptide systems in the fetus.

PMID- 18828927
TI  - Changing dental caries and periodontal disease patterns among a cohort of
      Ethiopian immigrants to Israel: 1999-2005.
AB  - BACKGROUND: Dental epidemiology has indicated that immigrants and minority ethnic
      groups should be regarded as high risk populations on the verge of oral health
      deterioration. The objectives of this study were to measure the changing pattern
      of dental caries, periodontal health status and tooth cleaning behaviour among a
      cohort of Ethiopian immigrants to Israel between the years 1999-2005. METHODS:
      Increment of dental caries and periodontal health status was recorded among a
      cohort of 672 Ethiopian immigrants, utilizing the DMFT and CPI indices. Data were
      gathered during 1999-2000 and five years later, during 2004-2005. Participants
      were asked about their oral hygiene habits in Ethiopia and in Israel five years
      since their immigration. RESULTS: Regarding dental caries, at baseline 70.1% of
      the examinees were caries-free, as compared to 57.3% after five years. DMFT had
      increased from 1.48 to 2.31. For periodontal health status, at baseline, 94.7%
      demonstrated no periodontal pockets (CPI scores 0-2) and 5.3% revealed
      periodontal pockets (CPI scores 3&4), compared to 75.6% and 24.4%, respectively
      after five years. At baseline, 74% reported cleaning their teeth exclusively
      utilizing chewing and cleaning sticks common in Ethiopia. After five years, 97%
      reported cleaning their teeth exclusively utilizing toothbrushes. CONCLUSION: The
      deterioration in the oral health status, especially the alarming and significant
      worsening of periodontal health status, among this immigrant group, emphasizes
      the need for health promotion and maintenance among immigrants and minority
      groups in changing societies. An "acclimatizing and integrating" model of oral
      health promotion among minority and immigrant groups is suggested.

PMID- 18828929
TI  - Barriers to accessing TB diagnosis for rural-to-urban migrants with chronic cough
      in Chongqing, China: a mixed methods study.
AB  - BACKGROUND: China is facing a significant tuberculosis epidemic among rural-to
      urban migrants, which poses a threat to TB control. This study aimed to
      understand the health seeking behaviour of and health systems responses to
      migrants and permanent urban residents suffering from chronic cough, in order to
      identify the factors influencing delays for both groups in receiving a TB
      diagnosis in urban China. METHODS: Combining a prospective cohort study of adult
      suspect TB patients and a qualitative study, the Piot model was used to analyze
      the health seeking behaviour of TB suspects among migrants and permanent urban
      residents, the factors influencing their decision and the responses by general
      health providers. Methods included a patient survey, focus group discussions with
      migrants in the general population, qualitative interviews with migrant and
      permanent resident TB suspects and TB patients as well as key stakeholders
      related to TB control and the management of migrants. RESULTS: Sixty eight
      percent of migrants delayed for more than two weeks before seeking care for
      symptoms suggestive of TB, compared to 54% of residents (p < 0.01). When they
      first decided to seek professional care, migrants were 1.5 times more likely than
      residents to use less expensive, community-level health services. Only 5% were
      ultimately referred to a TB dispensary. Major reasons for both patient and
      provider delay included lack of knowledge and mistrust of the TB control
      programme, lack of knowledge about TB (patients), and profit-seeking behaviour
      (providers). In the follow up survey, 61% of the migrants and 41% of the
      residents who still had symptoms gave up continuing to seek professional care,
      with a statistically significant difference between the two groups (p < 0.05).
      CONCLUSION: Rural-to-urban migrants are more likely than permanent residents to
      delay in seeking care for symptoms suggestive of TB in urban Chongqing. 'Patient
      ' and 'provider-' related factors interact to pose barriers to TB diagnosis for
      migrants, including: low awareness, and poor knowledge among both the general
      public and TB suspects about TB as a disease and about the TB control programme;
      low financial capacity to pay for care and diagnostic tests; and inadequate use
      of diagnostic tests and referral to TB dispensaries by general health providers.

PMID- 18828928
TI  - Cryopreservation/transplantation of ovarian tissue and in vitro maturation of
      follicles and oocytes: challenges for fertility preservation.
AB  - Cryopreservation of ovarian tissue and in vitro follicle maturation are two
      emerging techniques for fertility preservation, especially in cancer patients.
      These treatment regimes are opening up more options and allow for more suitable
      choices to preserve fertility according to the patient's specific circumstances.
      If these technologies are to become widely accepted, they need to be safe, easy
      to perform and must obtain favorable results. The generation of healthy eggs with
      the normal genetic complement and the ability to develop into viable and healthy
      embryos requires tight regulation of oocyte development and maturation. Novel
      freezing techniques such as vitrification, along with whole ovary
      cryopreservation and three-dimensional follicle cultures, have shown favorable
      outcomes. The scope of this article is to take a comprehensively look at the
      challenges still faced in order for these novel technologies to be routinely
      employed with the aim of successful fertility preservation.

PMID- 18828930
TI  - Progression-free survival as a surrogate endpoint in advanced breast cancer.
AB  - OBJECTIVES: Progression-free survival (PFS) has not been validated as a surrogate
      endpoint for overall survival (OS) for anthracycline (A) and taxane-based (T)
      chemotherapy in advanced breast cancer (ABC). Using trial-level, meta-analytic
      approaches, we evaluated PFS as a surrogate endpoint. METHODS: A literature
      review identified randomized, controlled A and T trials for ABC. Progression
      based endpoints were classified by prospective definitions. Treatment effects
      were derived as hazard ratios for PFS (HRPFS) and OS (HROS). Kappa statistic
      assessed overall agreement. A fixed-effects regression model was used to predict
      HROS from observed HRPFS. Cross-validation was performed. Sensitivity and
      subgroup analyses were performed for PFS definition, year of last patient
      recruitment, line of treatment, and constant rate assumption. RESULTS: Sixteen A
      and fifteen T trials met inclusion criteria, producing seventeen A (n = 4,323)
      and seventeen T (n = 5,893) trial-arm pairs. Agreement (kappa statistic) between
      the direction of HROS and HRPFS was 0.71 for A (p = .0029) and 0.75 for T (p =
      .0028). While HRPFS was a statistically significant predictor of HROS for both A
      (p = .0019) and T (p = .012), the explained variances were 0.49 (A) and 0.35 (T).
      In cross-validation, 97 percent of the 95 percent prediction intervals crossed
      the equivalence line, and the direction of predicted HROS agreed with observed
      HROS in 82 percent (A) and 76 percent (T). Results were robust in sensitivity and
      subgroup analyses. CONCLUSIONS: This meta-analysis suggests that the trial-level
      treatment effect on PFS is significantly associated with the trial-level
      treatment effect on OS. However, prediction of OS based on PFS is surrounded with
      uncertainty.

PMID- 18828931
TI  - Utilization patterns of diagnostic imaging across the late life course: a
      population-based study in Ontario, Canada.
AB  - OBJECTIVES: Due to the aging baby boom population, utilization rates of
      diagnostic imaging (i.e., X-ray, CT, and MRI scanning) have risen rapidly
      relative to other health services. The aim of this study is to investigate the
      utilization patterns of outpatient diagnostic imaging services (X-ray, CT, and
      MRI) across the late life course (65 years and older). METHODS: A population
      based retrospective cohort study was conducted for the period April 1, 2005, to
      March 31, 2006. All Ontario residents aged 65+ and eligible for government health
      insurance were included in the analysis. RESULTS: Utilization of diagnostic
      imaging followed an inverted U-pattern: increasing with advancing age, peaking in
      the 80-84 age group for CT scans and in the 70-74 age group for MRI and X-rays,
      and then declining in the later years. Overall, females received significantly
      more X-rays than males (p < .01), but males received significantly more CT and
      MRI scans (p < .01). A small proportion of high-users of radiology services
      accounted for a large proportion of overall utilization. Finally, our analysis
      revealed that a disproportionately large proportion of high-users of MRI services
      were in the highest SES quintile. No SES differences were observed for X-ray or
      CT scans. CONCLUSIONS: Population aging will lead to increased demand for
      healthcare services. Utilization of outpatient diagnostic imaging services is
      associated with age, gender, and SES. Given the increasing demand and the limited
      resources available, there may be a need for programs to target underserved
      populations to reduce remediable inequities. Whereas patient-level decisions
      regarding the use of diagnostic imaging are rightfully determined on the basis of
      clinical factors, allocation decisions should also be informed by the ethical
      principles of equity and fairness.

PMID- 18828932
TI  - Putting National Institute for Health and Clinical Excellence guidance into
      practice: a cost minimization model of a national roll-out of liquid based
      cytology in England.
AB  - OBJECTIVES: In 2003, the National Institute for Health and Clinical Excellence
      (NICE) advised that liquid based cytology (LBC) should be adopted for cervical
      screening in England. The aim of this study was to explore the cost implications
      of implementing the NICE guidance in cytology laboratories. The ThinPrep
      technology was used as the case study. METHODS: An optimization model was
      developed to analyze options for leasing alternative LBC processing machines with
      different capacities. Variables entered in the model included: the cost of the
      contract with the supplier, the laboratory labor cost, and inter-laboratory
      transport costs. All costs referred to the 2005-06 financial year. A simulation
      program calculated mileages within laboratory networks. Alternative strategies
      for contracting by laboratories acting independently and by Quality Assessment
      Regional Centres (QARC) were analyzed. RESULTS: Centralizing the processing of
      specimens in "hub and spoke" laboratory networks was the least costly strategy.
      Total annual costs for England using existing transport links were 14,807,000 UK
      pounds for 5-year contracts. If all laboratories installed processors, the annual
      cost for 5-year contracts placed by QARCs was 14,941,000 UK pounds compared with
      16,359,000 pounds if the laboratories placed their own contracts. Three-year
      contracts averaged an additional 1 million UK pounds: 15,912,000 pounds for
      networks and 17,304,000 pounds for independent laboratory contracts. CONCLUSIONS:
      Deciding on the mode of implementation of a NICE guidance can be challenging for
      decision makers. These cost minimization appraisal techniques are equally
      applicable to national screening programs in general and to other health
      technologies for which there are significant cost implications associated with
      innovative policy directives.

PMID- 18828933
TI  - Shift from first generation antipsychotics to olanzapine may improve health
      related quality of life of stable but residually symptomatic schizophrenic
      outpatients: a prospective, randomized study.
AB  - OBJECTIVES: The aim of this study was to elucidate, whether shift from first
      generation antipsychotics (FGA) to olanzapine can affect health-related quality
      of life (HRQoL) of residually symptomatic schizophrenic outpatients. METHODS:
      Patients were randomized to either olanzapine or to continuation on their FGA.
      The 15D-measured HRQoL at baseline and end-point (after 12 weeks) was compared.
      RESULTS: Patients (n = 21) randomized to olanzapine achieved better HRQoL than
      those (n = 21) who continued on their FGA. This difference on the 15D (0.048 on a
      0-1 scale; p = .037) was clinically important and comparable to that resulting
      from common surgical interventions, for example, hip or knee replacement.
      CONCLUSIONS: HRQoL of stable outpatients with residual symptoms or adverse
      effects may improve substantially after shift from FGAs to olanzapine.

PMID- 18828934
TI  - Locating systematic reviews of test accuracy studies: how five specialist review
      databases measure up.
AB  - OBJECTIVES: The aim of this study was to examine location of systematic reviews
      of test accuracy in five specialist review databases: York CRD's DARE and HTA
      databases, Medion (University of Maastricht), C-EBLM (International Federation of
      Clinical Chemistry), and the ARIF in-house database (University of Birmingham).
      METHODS: Searches were limited to the period 1996-2006. Test accuracy reviews
      were located using in-house diagnostic search filters and with help from database
      producers where databases were not confined to test accuracy reviews. References
      were coded according to disease area, review purpose, and test application. Ease
      of use, volume, overlap, and content of databases was noted. RESULTS: A large
      degree of overlap existed between databases. Medion contained the largest number
      (n = 672) and the largest number of unique (n = 328) test accuracy references. A
      combination of three databases identified only 76% of test reviews. All databases
      were rated as easy to search but varied with respect to timeliness and
      compatibility with reference management software. Most reviews evaluated test
      accuracy (85%) but the HTA database had a larger proportion of cost-effectiveness
      and screening reviews and C-EBLM more reviews addressing early test development.
      Most reviews were conducted in secondary care settings. CONCLUSIONS: Specialist
      review databases offer an essential addition to general bibliographic databases
      where application of diagnostic method filters can compromise search sensitivity.
      Important differences exist between databases in terms of ease of use and
      content. Our findings raise the question whether the current balance of research
      setting, in particular the predominance of research on tests used in secondary
      care, matches the needs of decision makers.

PMID- 18828935
TI  - Guidance for considering ethical, legal, and social issues in health technology
      assessment: application to genetic screening.
AB  - OBJECTIVES AND METHODS: Many authors have argued that ethical, legal, and social
      issues ("ELSIs") should be explicitly integrated into health technology
      assessment (HTA), yet doing so poses challenges. This discussion may be
      particularly salient for technologies viewed as ethically complex, such as
      genetic screening. Here we provide a brief overview of contemporary discussions
      of the issues from the HTA literature. We then describe key existing policy
      evaluation frameworks in the fields of disease screening and public health
      genomics. Finally, we map the insights from the HTA literature to the policy
      evaluation frameworks, with discussion of the implications for HTA in genetic
      screening. RESULTS AND CONCLUSIONS: A critical discussion in the HTA literature
      considers the definition of ELSIs in HTA, highlighting the importance of thinking
      beyond ELSIs as impacts of technology. Existing HTA guidance on integrating ELSIs
      relates to three broad approaches: literature synthesis, involvement of experts,
      and consideration of stakeholder values. The thirteen key policy evaluation
      frameworks relating to disease screening and public health genomics identified a
      range of ELSIs relevant to genetic screening. Beyond straightforward impacts of
      screening, these ELSIs require consideration of factors such as the social and
      political context surrounding policy decisions. The three broad approaches to
      addressing ELSIs described above are apparent in the screening/genomics
      literatures. In integrating these findings we suggest that the method chosen for
      addressing ELSIs in HTA for genetic screening may determine which ELSIs are
      prioritized; and that an important challenge is the lack of guidance for
      evaluating such methods.

PMID- 18828936
TI  - Why ethics should be part of health technology assessment.
AB  - From the heydays of HTA in the 1970s, it has been argued that ethics should be a
      part of HTA. Despite more than 30 years with repeated intentions, only few HTA
      reports include ethical analysis, and there is little agreement on methods for
      integrating ethics. This poses the question of why it is so important to
      integrate ethics in HTA? The article analyzes ten arguments for making ethics
      part of HTA. The validity of the arguments depend on what we mean by
      "integrating," "ethics," and "HTA." Some of the counterarguments explain why it
      has taken so long to integrate ethics in HTA and why there are so many ethical
      approaches. Nevertheless, some of the arguments for making ethics part of HTA
      appear to be compelling. Health care is a moral endeavor, and the vast potential
      of technology poses complex moral challenges. A thorough assessment of technology
      would include reflection on these moral aspects. Ethics provides such a moral
      reflection. Health technology is a way to improve the life of human individuals.
      This involves questions of what "the good life" is, and hence ethical issues.
      Trying to ignore such questions may inflict with the moral foundation of health
      care: to help people. Additionally, HTA is an evaluation, and as such also a
      reflection on values. Hence, there is a profound affinity between HTA and ethics.
      Accordingly, ethics cannot be "integrated" in HTA as ethics is already a
      constitutive part of HTA. However, ethics can be acknowledged and emphasized.

PMID- 18828937
TI  - Reuse of single use medical devices in Canada: clinical and economic outcomes,
      legal and ethical issues, and current hospital practice.
AB  - OBJECTIVES: The aim of this study was to assess the evidence that reuse of
      medical devices marketed for single use only (SUDs) is safe, effective and cost
      effective, and to consider the use and health services impact of this practice in
      Canada. METHODS: A systematic review was performed of studies that reported
      clinical or economic outcomes following reuse of SUDs in humans. Direct costs of
      adverse health events associated with SUD reuse and indications of budget impact
      were obtained using data for devices for laparoscopic cholecystectomy and
      coronary angioplasty. Legal and ethical issues were reviewed, drawing on material
      relevant to Canada. Data on current reuse of SUDs were obtained through a survey
      of Canadian acute care hospitals. RESULTS: Studies of variable quality suggested
      that SUD reuse could be safe and effective, and would give cost savings, if there
      were no adverse events. Eliminating reuse of SUDs for laparoscopic
      cholecystectomy and coronary angioplasty would add less than 0.1 percent to costs
      of the procedures over 1 year. Adverse health events associated with device reuse
      create liability risks; patients should be informed of any known or foreseeable
      risks of reuse. Most of the 28 percent (111/398) of acute hospitals that
      reprocess SUDs do so in-house. Some do not have a written policy or an incident
      reporting mechanism. CONCLUSIONS: There is insufficient evidence to establish the
      safety, efficacy and cost-effectiveness of reusing SUDs. Legal and ethical issues
      require attention to minimize liability and maintain patient safety and trust.
      Some hospitals that reprocess SUDs do not have adequate documentation. These
      findings do not support the reuse of SUDs in Canadian hospitals.

PMID- 18828938
TI  - Economic evaluations conducted by Canadian health technology assessment agencies:
      where do we stand?
AB  - OBJECTIVES: To examine the production of Health Technology Assessments (HTAs)
      with economic evaluations (EEs) conducted by Canadian HTA agencies. METHODS: This
      research used a three-step approach: (i) the Web sites of five Canadian
      organizations promoting HTA were searched to identify HTA reports with EEs; (ii)
      HTA agencies were surveyed to verify that our information was complete with
      respect to HTA activities and to describe the factors that influence the HTA
      process in Canada (i.e., selection of HTA topics, execution, dissemination of
      results and future trends); (iii) HTAs with EEs were appraised in terms of study
      design, retrieval of clinical and economic evidence, resource utilization and
      costing, effectiveness measures, treatment of uncertainty as well as presence of
      a budget impact analysis (BIA), and policy recommendations. RESULTS: Two hundred
      forty-nine HTA reports were identified of which 19 percent included EEs (n = 48).
      Decision analytic techniques were used in approximately 75 percent of the forty
      eight EEs and probabilistic sensitivity analyses were commonly used by all
      agencies to deal with parameter uncertainty. BIAs or policy recommendations were
      given in 50 percent of the evaluations. Differences between agencies were
      observed in terms of selection of topics, focus of assessment and production of
      HTA (e.g., in-house activities). Major barriers to the conduct of HTAs with EEs
      were capacity, a lack of interest by decision makers and a lack of robust
      clinical information. CONCLUSIONS: The results of this research point to the need
      for increased HTA training, collaboration, evidence synthesis, and use of
      pragmatic "real world" evaluations.

PMID- 18828939
TI  - Factors influencing the quality of medical documentation when a paper-based
      medical records system is replaced with an electronic medical records system: an
      Iranian case study.
AB  - OBJECTIVES: Information technology is a rapidly expanding branch of science which
      has affected other sciences. One example of using information technology in
      medicine is the Electronic Medical Records system. One medical university in Iran
      decided to introduce such system in its hospital. This study was designed to
      identify the factors which influence the quality of medical documentation when
      paper-based records are replaced with electronic records. METHODS: A set of 300
      electronic medical records was randomly selected and evaluated against eleven
      checklists in terms of documentation of medical information, availability,
      accuracy and ease of use. To get the opinion of the care-providers on the
      electronic medical records system, ten physicians and ten nurses were interviewed
      by using of semi-structured guidelines. The results were also compared with a
      prior study with 300 paper-based medical records. RESULTS: The quality of
      documentation of the medical records was improved in areas where nurses were
      involved, but those parts which needed physicians' involvement were actually
      worse. High workloads, shortage of bedside hardware and lack of software features
      were prominent influential factors in the quality of documentation. The results
      also indicate that the retrieval of information from the electronic medical
      records is easier and faster, especially in emergency situations. CONCLUSIONS:
      The electronic medical records system can be a good substitute for the paper
      based medical records system. However, according to this study, some factors such
      as low physician acceptance of the electronic medical record system, lack of
      administrative mechanisms (for instance supervision, neglecting physicians and/or
      nurses in the development and implementation phases and also continuous
      training), availability of hardware as well as lack of specific software features
      can negatively affect transition from a paper-based system to an electronic
      system.

PMID- 18828940
TI  - How is magnetic resonance imaging used in Iran?
AB  - OBJECTIVES: Analysis of and understanding the utilization patterns of diagnostic
      imaging technologies is important for planning health systems especially in
      middle- and low-income countries. Almost all published studies have been focused
      on utilization trends or utilization rates of magnetic resonance imaging (MRI)
      over time and little has been published about utilization patterns of MRI. This
      study aims to identify and describe the utilization pattern of MRI in Iran.
      METHODS: Data was collected from referrals and MRI reports of the population
      covered by one of the largest insurance organizations (Social Security
      Organization [SSO]) with more than 27 million beneficiaries in the Country. We
      focused on patients who had undergone an MRI examination during 1 month (October
      13 to November 12), 2005. The data collected consisted of 1,656 referrals for MR
      imaging and 1,547 MRI reports. RESULTS: No clear association was found between
      the number of referrals per 100,000 population and the number of MRI machines per
      100,000 population (r = 0.30; p = .13). Neurosurgeons, orthopedists, and
      neurologists contributed to more than 88 percent of MRI utilization. The Spinal
      column (55 percent), brain (25.5 percent), and knee (11.0 percent) were the most
      common parts of the body scanned by MRI. CONCLUSIONS: Having identified some of
      the most frequent users of MRI technology, any plan for modifying or improving
      MRI use should focus mainly on these specialties. International evidence on using
      the technology for examining brain and spine indicate that MRI is mainly used in
      diagnosing the central nervous system (CNS) diseases.

PMID- 18828941
TI  - Integrating health economics modeling in the product development cycle of medical
      devices: a Bayesian approach.
AB  - OBJECTIVES: Medical device companies are under growing pressure to provide health
      economic evaluations of their products. Cost-effectiveness analyses are commonly
      undertaken as a one-off exercise at the late stage of development of new
      technologies; however, the benefits of an iterative use of economic evaluation
      during the development process of new products have been acknowledged in the
      literature. Furthermore, the use of Bayesian methods within health technology
      assessment has been shown to be of particular value in the dynamic framework of
      technology appraisal when new information becomes available in the life cycle of
      technologies. METHODS: In this study, we set out a methodology to adapt these
      methods for their application to directly support investment decisions in a
      commercial setting from early stages of the development of new medical devices.
      RESULTS AND CONCLUSIONS: Starting with relatively simple analysis from the very
      early development phase and proceeding to greater depth of analysis at later
      stages, a Bayesian approach facilitates the incorporation of all available
      evidence and would help companies to make better informed choices at each
      decision point.

PMID- 18828942
TI  - Contribution of economic evaluation to decision making in early phases of product
      development: a methodological and empirical review.
AB  - BACKGROUND: Economic evaluation as an integral part of health technology
      assessment is today mostly applied to established technologies. Evaluating
      healthcare innovations in their early states of development has recently
      attracted attention. Although it offers several benefits, it also holds
      methodological challenges. OBJECTIVES: The aim of our study was to investigate
      the possible contributions of economic evaluation to industry's decision making
      early in product development and to confront the results with the actual use of
      early data in economic assessments. METHODS: We conducted a literature research
      to detect methodological contributions as well as economic evaluations that used
      data from early phases of product development. RESULTS: Economic analysis can be
      beneficially used in early phases of product development for various purposes
      including early market assessment, R&D portfolio management, and first
      estimations of pricing and reimbursement scenarios. Analytical tools available
      for these purposes have been identified. Numerous empirical works were detected,
      but most do not disclose any concrete decision context and could not be directly
      matched with the suggested applications. CONCLUSIONS: Industry can benefit from
      starting economic evaluation early in product development in several ways.
      Empirical evidence suggests that there is still potential left unused.

PMID- 18828943
TI  - Health technology assessment use and dissemination by patient and consumer
      groups: why and how?
AB  - OBJECTIVES: Although increasing effort is being devoted to developing strategies
      to increase knowledge transfer and the uptake of health technology assessment
      (HTA) by various stakeholders, very little is known about the utilization and
      dissemination of HTA findings by patient and consumer organizations. The goal of
      this study is to understand how and why patient and consumer organizations use
      HTA findings within their organizations, and what factors influence how and when
      they communicate their findings to members or other organizations. METHODS: We
      examined the use and dissemination of four controversial HTA reports by sixteen
      patient and consumer organizations in Ontario and Quebec. We gathered data from
      semistructured interviews conducted between December 2006 and April 2007.
      RESULTS: Although HTA findings are often used by the patient and consumer
      organizations, key differences were observed in exactly how the four HTA reports
      were used. Three types of use (instrumental, conceptual, and symbolic) are
      reported and illustrated. We highlight the importance of the organization's
      mission and knowledge base in explaining the types of use observed. CONCLUSIONS:
      We contend that the use and dissemination of HTA reports by specific groups could
      help in widening the debate around controversial health technologies. The
      implications and opportunities for HTA agencies relate to the following: (i)
      identification of "lay" organizations that could help in disseminating results;
      (ii) acknowledgement of a "lay" audience for HTA findings; (iii) strategic
      inclusion of advocacy groups during the assessment process for highly
      controversial technologies; and (iv) contribution of these organizations to the
      push efforts of knowledge transfer.

PMID- 18828944
TI  - Comparison of four contingent valuation methods to estimate the economic value of
      a pneumococcal vaccine in Bangladesh.
AB  - OBJECTIVES: To compare four contingent valuation elicitation methods as a means
      to estimate the value of a pneumococcal vaccine in Bangladesh and to test if the
      elicitation methods are subject to bias and if they produce valid responses.
      METHODS: Three hundred sixty-one households with at least one child under 5 years
      of age were recruited in Dhaka, Bangladesh. Subjects were cluster-randomized to
      various elicitation methods: open-ended, dichotomous choice (at one of two asking
      prices), payment card (one of two cards with differing ranges). The dichotomous
      choice method was then followed up with a bidding game methodology, with the
      dichotomous choice price acting as the starting price for the bidding game.
      Analysis focused on summary statistics, demand curve estimation and multivariate
      regression analysis to test for validity and bias. RESULTS: Thirty-one households
      refused to participate, leaving a total of 330 participating households (a 91.4
      percent response rate). Willingness to pay estimates varied significantly across
      the methods (p < .001), with average estimates varying between $2.34 and $18
      (US). The open-ended elicitation method was found to produce highly inflated
      values that were insensitive to construct validity tests. The dichotomous choice
      method produced quantity (demand) estimates rather than value estimates, and
      there was some evidence of yea-saying. The payment card elicitation method was
      found to be affected by range bias. The bidding game elicitation method was found
      to be less sensitive to starting point bias and yea-saying. CONCLUSIONS:
      Different elicitation format do give rise to different demand curves; however,
      this may be partially due to the fact that they do not measure the same outcome.
      For example, the dichotomous choice format produces a demand curve, while the
      payment card, open-ended and bidding game produce inverse demand curves. All
      formats are prone to multiple biases. When choosing an elicitation format, it is
      important to first consider the purpose and use of the data. Each elicitation
      method has strengths and weaknesses and can be used for different purposes in
      technology assessment.

PMID- 18828945
TI  - Do individuals consider expected income when valuing health states?
AB  - OBJECTIVES: The purpose of this study was to empirically explore whether
      individuals take their expected income into consideration when directly valuing
      predefined health states. This was intended to help determine how to handle
      productivity costs due to morbidity in a cost-effectiveness analysis. METHODS:
      Two hundred students each valued four hypothetical health states by using time
      trade-off (TTO) and a visual analogue scale (VAS). The students were randomly
      assigned to two groups. One group was simply asked, without mentioning income, to
      value the different health states (the non-income group). The other group was
      explicitly asked to consider their expected income in relation to the health
      states in their valuations (the income group). RESULTS: For health states that
      are usually assumed to have a large effect on income, the valuations made by the
      income group seemed to be lower than the valuations made by the non-income group.
      Among the students in the non-income group, 96 percent stated that they had not
      thought about their expected income when they valued the health states. In the
      income group, 40 percent believed that their expected income had affected their
      valuations of the health states. CONCLUSION: The results show that, as long as
      income is not mentioned, most individuals do not seem to consider their expected
      income when they value health states. This indicates that productivity costs due
      to morbidity are not captured within individuals' health state valuations. These
      findings, therefore, suggest that productivity costs due to morbidity should be
      included as a cost in cost-effectiveness analyses.

PMID- 18828946
TI  - Estimating the implicit value of statistical life based on public interventions
      implemented in The Netherlands.
AB  - OBJECTIVES: In the Netherlands, allocation decisions have not yet been explicitly
      based on the Value of Statistical Life. However, when policy makers decide
      whether or not to implement life saving interventions this trade-off is made
      implicitly. This study aimed to gain insights into this trade-off, hereafter
      referred to as Implicit Value of Statistical Life (IVSL), by means of a
      retrospective investment analysis of life saving interventions implemented in the
      Netherlands. METHODS: A literature search was conducted to find life saving
      intervention cases meeting the requirements for IVSL calculation. A final sample
      of ten cases was included in the study concerning interventions implemented in
      different societal sectors. For each case, an IVSL estimate was calculated
      according to a uniform method. RESULTS: IVSL estimates derived from the
      intervention cases differed considerably and ranged from 1 euro to almost 11
      million euros. Differences were most extreme when comparing IVSL estimates
      concerning interventions implemented in different societal sectors. However, IVSL
      estimates also varied greatly between interventions in the same sector and even
      within the same interventions when critical assumptions were altered. CONCLUSION:
      Our findings suggest that there are great imbalances between societal investments
      for preventing a statistical death. This highlights the need for further
      deliberation about how to improve transparency of policy decisions. An approach
      ex ante determining the Value of Statistical Life by means of empirical methods
      and based on societal preferences might circumvent the problems associated with
      the IVSL and needs further exploration.

PMID- 18828947
TI  - Budgeting and health technology assessment: first evidence obtained from proposal
      forms used to submit the adoption of new technology.
AB  - OBJECTIVES: The aim of this study was to benchmark the proposal forms used by a
      sample of Italian hospitals to inform the budget process for the adoption of new
      technology to understand the relationship with the guidelines provided by the
      Health Technology Assessment (HTA) literature. METHODS: A literature review was
      first undertaken to identify the frameworks developed to support decision making
      regarding new technology at a hospital level. A checklist of criteria drawn up
      according to five main perspectives (technology, patient, organization,
      economics, and level of evidence) has been formalized to review and compare the
      collected proposal forms. RESULTS: The "technology" perspective appears to have
      been broadly covered. The "patient" perspective has focused to clinical issues
      and partially neglects other dimensions such as patient satisfaction and
      potential adverse events. The "organization" dimension has paid little attention
      to change management. The "economics" dimension has been broadly covered, even
      though a sensitivity analysis has not been considered. The "level of evidence"
      that is required for submitting the proposal form is little. CONCLUSIONS: The
      proposal forms used to inform the budget process regarding the adoption of new
      technology are accountable for a limited set of dimensions from among those
      proposed in literature. Further research is required to understand how to render
      technology assessment multidimensional, multidisciplinary, evidence-based, and
      accountable at a hospital level.

PMID- 18828948
TI  - Harmonization of evidence requirements for health technology assessment in
      reimbursement decision making.
AB  - As more countries use HTA to inform decisions on the reimbursement of health
      technologies, harmonization of evidence requirements between jurisdictions has
      been proposed, mainly on the grounds of improved efficiency. Harmonization has
      the potential to avoid duplication of effort for both manufacturers and HTA
      bodies involved in preparing and reviewing HTA submissions for innovative
      technologies. However, it also carries risks of loss of local control over
      decisions, the application of general data standards which are not universally
      accepted and slowing the rate of development of innovation in the analytical
      disciplines supporting HTA. This study reviews the issues associated with
      harmonization taking into account the perspectives of the multiple stakeholders.
      This study draws on experiences from recent initiatives intended to promote the
      harmonization of HTA and experience from related fields, particularly regulatory
      approval of new medical technologies.

PMID- 18828949
TI  - Early identification and assessment of new and emerging health technologies:
      actions, progress, and the future direction of an international collaboration-
      EuroScan.
AB  - OBJECTIVES: To report on a workshop, and subsequent discussions, that reviewed
      the achievements and progress of the EuroScan collaboration since its
      establishment in 1999 to share information on the methods and results of early
      identification and assessment of new and emerging health technologies; considered
      challenges to the collaboration; and discussed its possible future direction.
      METHODS: A workshop was held in Stockholm in September 2006, with thirty-two
      participants from ten countries and representatives from EuroScan member
      agencies, policy makers involved in policy or decision making relating to new
      technologies, and invited external commentators from international HTA networks.
      The workshop used a mix of presentations, panel and audience discussions, and
      small group work to consider the achievements and challenges put forward.
      RESULTS: EuroScan has developed as a sustainable network, and has made progress
      on all tasks in its initial action plan, with the EuroScan information sharing
      database on new and emerging technologies being one of the collaboration's key
      achievements. Identified immediate concerns for the network included
      consideration of the impact of its current name and membership model;
      acknowledgement and publication of the full range of benefits of membership;
      contribution to and development of the database to encourage increased
      information sharing; and EuroScan's ongoing interaction with the wider HTA world.
      CONCLUSIONS: The workshop was a useful mechanism for reviewing the work of
      EuroScan and for creating a platform to take the collaboration forward. The
      workshop affirmed the benefits of the network to individual members; posed some
      significant challenges to the network to consider; and acted as a stimulus for an
      interim name change to better represent the global membership, and a major review
      of the EuroScan database of identified and assessed emerging health technologies.

PMID- 18828950
TI  - Hypothalamic orexins/hypocretins as regulators of breathing.
AB  - It was suggested half a century ago that electrical impulses from the lateral
      hypothalamic area stimulate breathing. It is now emerging that these effects may
      be mediated, at least in part, by neurons containing orexin neuropeptides (also
      known as hypocretins). These cells promote wakefulness and consciousness, and
      their loss results in narcolepsy. Recent data also show that orexin neurons
      directly project to respiratory centres in the brainstem, which express orexin
      receptors, and where injection of orexin stimulates breathing. Because orexin
      neurons receive inputs that signal metabolic, sleep/wake and emotional states, it
      is tempting to speculate that they may regulate breathing according to these
      parameters. Knockout of the orexin gene in mice reduces CO2-induced increases in
      breathing by approximately 50% and increases the frequency of spontaneous sleep
      apneas. The relationship between orexins and breathing may be bidirectional: the
      rate of breathing controls acid and CO2 levels, and these signals alter the
      electrical activity of orexin neurons in vitro. Overall, these findings suggest
      that orexins are important for the regulation of breathing and may potentially
      play a role in the pathophysiology and medical treatment of respiratory
      disorders.

PMID- 18828951
TI  - The good life: living for health and a life without risks? On a prominent script
      of nutrigenomics.
AB  - Like all scientific innovations, nutrigenomics develops through a constant
      interplay with society. Normative assumptions, embedded in the way researchers
      formulate strands of nutrigenomics research, affect this interplay. These
      assumptions may influence norms and values on food and health in our society. To
      discuss the possible pros and cons of a society with nutrigenomics, we need to
      reflect ethically on assumptions rooted in nutrigenomics research. To begin with,
      we analysed a set of scientific journal articles and explicated three normative
      assumptions embedded in the present nutrigenomics research. First, values
      regarding food are exclusively explained in terms of disease prevention. Health
      is therefore a state preceding a sum of possible diseases. Second, it is assumed
      that health should be explained as an interaction between food and genes. Health
      is minimised to quantifiable health risks and disease prevention through food
      gene interactions. The third assumption is that disease prevention by
      minimisation of risks is in the hands of the individual and that personal risks,
      revealed either through tests or belonging to a risk group, will play a large
      role in disease prevention. Together, these assumptions suggest that the good
      life (a life worth living, with the means to flourish and thrive) is equated with
      a healthy life. Our thesis is that these three normative assumptions of
      nutrigenomics may strengthen the concerns related to healthism, health anxiety,
      time frames and individual responsibilities for health. We reflect on these
      ethical issues by confronting them in a thought experiment with alternative,
      philosophical, views of the good life.

PMID- 18828952
TI  - Modulation of rat neutrophil function in vitro by cis- and trans-MUFA.
AB  - In the present study, the effects of trans-MUFA, elaidic acid (EA; 18 : 1-9t) and
      vaccenic acid (VA; 18 : 1-11t) on rat neutrophil functions were compared with
      those of cis-monounsaturated oleic acid (OA) (18 : 1-9c) and saturated stearic
      acid (SA; 18 : 0) (10-150 microm). Trans-fatty acids enhanced neutrophil
      phagocytic capacity, superoxide (O2-) and hydrogen peroxide production, and
      candidacidal activity. The same effects were observed for OA. Cells treated with
      trans-MUFA showed reduced production of NO, whereas those treated with OA showed
      an increase in production. Treatment with SA did not provoke significant effect
      on the parameters investigated. The increase in O2- production induced by MUFA
      was not observed when diphenyleneiodonium, an NADPH oxidase inhibitor, was added
      to the medium. This finding suggests that MUFA stimulate neutrophil NADPH oxidase
      activity. The addition of 3-[1-[3-(dimethylamino)propyl]-1H-indol-3-yl]-4-(1H
      indol-3-yl)-1H-pyrrole-2,5-dione, a protein kinase C (PKC) inhibitor, and
      wortmannin, a phosphatidylinositol-3 kinase (PI3K) inhibitor, did not affect O2-
      production induced by MUFA. Therefore, the mechanisms by which MUFA stimulate
      NADPH oxidase are not dependent on PKC and do not seem to involve PI3K.
      Experiments using Zn2+, an inhibitor of NADPH oxidase H+ channel, indicated that
      MUFA activate the NADPH oxidase complex in rat neutrophil due to opening of H+
      channel.

PMID- 18828953
TI  - Dispersion of the P wave as a test for cardiac autonomic function in diabetic
      children.
AB  - OBJECTIVE: We aimed, in this study, to compare dispersion of the p wave in
      patients with type 1 diabetes to nondiabetic control subjects, and to investigate
      the relationship between the dispersion of the p wave and cardiac autonomic
      dysfunction in diabetic children. METHODS: We enrolled 49 patients with type 1
      diabetes, and 32 age- and sex-matched healthy subjects, measuring the Valsalva
      ratio, resting heart rate, and orthostatic hypotension in all. The duration of
      the p wave was measured manually on a high-resolution computer screen.
      Dispersion, defined as the difference between maximum and minimum durations of
      the p waves, was also measured in the 12-lead electrocardiogram before and after
      the Valsalva maneuver. RESULTS: The mean age of the patients and their controls
      were 14.2 +/- 4.8 years, and 12.7 +/- 4.5 years, respectively. The mean duration
      of diabetes had been 6.2 +/- 4.6 years. Maximal and minimal values for the
      duration of the p wave were significantly decreased in the diabetic children,
      with the dispersion itself significantly increased. Values for the dispersion in
      the diabetic subjects were similar before and after the Valsalva maneuver,
      whereas dispersion was found significantly increased after this maneuver in the
      controls. The differences in the Valsalva ratio, resting heart rate, and
      orthostatic hypotension between the groups, on the other hand, were not found to
      be statistically significant. CONCLUSION: The noted increase in the dispersion of
      the p wave in diabetic children reveals the onset of cardiac electrophysiological
      heterogeneity before it is possible to detect parasympathetic and sympathetic
      dysfunction with other tests.

PMID- 18828954
TI  - Atrioventricular block following implantation of a stent in the oval fossa.
AB  - A neonate weighing 2.8 kilograms underwent the staged hybrid procedure for
      palliation of hypoplastic left heart syndrome. Within 6 hours following placement
      of a stent to retain patency of the interatrial communication, the infant
      developed second degree atrioventricular block, which resolved within 24 hours.
      Four days later, the patient developed complete atrioventricular dissociation.
      Removal of the stent was followed by recovery of atrioventricular conduction.

PMID- 18828955
TI  - The syndrome of cardiac failure in adults with congenitally corrected
      transposition.
AB  - OBJECTIVES: To assess neurohormonal activation of cardiac failure in adults with
      congenitally corrected transposition, and to determine the most sensitive marker
      for recognition of the cardiac failure. BACKGROUND: The onset of morphologically
      right ventricular dysfunction is unpredictable in patients with congenitally
      corrected transposition, the combination of discordant atrioventricular and
      ventriculo-arterial connections, and its markers are unknown. METHODS: We
      measured amino terminal pro brain natriuretic peptide in 19 patients, aged 35
      plus or minus 13.1 years, and in 19 control subjects. Morhologically right
      ventricular function was assessed by echocardiography, including tissue Doppler
      echocardiography and magnetic resonance imaging or multislice computed
      tomography. RESULTS: The patients showed a highly significant increase in the
      levels of amino terminal pro brain natriuretic peptide, the levels being
      significantly elevated even in asymptomatic patients. Left atrial dimensions were
      larger in patients, and significantly lower tissue Doppler echocardiographic
      velocities were measured at the lateral site of the tricuspid annulus and at the
      basal segment of the interventricular septum. The ejection fraction of the
      morphologically right ventricle correlated significantly with the levels of brain
      natriuretic peptide, and with left atrial dimensions. CONCLUSIONS: Neurohormonal
      activation is present in patients with congenitally corrected transposition even
      when they are asymptomatic. It is correlated with left atrial dimensions and
      tissue Doppler echocardiographic parameters. Levels of brain natriuretic peptide,
      and peak tricuspid early diastolic annular velocity, are the earliest and most
      sensitive markers of morphologically right ventricular dysfunction.

PMID- 18828956
TI  - Implantation of drug-eluting stents for relief of obstructed infra-cardiac
      totally anomalous pulmonary venous connection in isomerism of the right atrial
      appendages.
AB  - We describe an infant with severe obstruction of infra-cardiac totally anomalous
      pulmonary venous connection associated with right isomerism, atrioventricular
      septal defect, pulmonary atresia, and multiple aortopulmonary collateral
      arteries. Implantation of a stent into the obstructed descending vertical vein
      provided effective palliation, with a dramatic increase in saturations of oxygen
      obviating the need for urgent high-risk surgery.

PMID- 18828957
TI  - Frequency of self-monitoring of blood glucose in patients with type 2 diabetes:
      association with hypoglycaemic events.
AB  - OBJECTIVE: The objective of this study is to describe current self-monitoring of
      blood glucose (SMBG) practice for patients with type 2 diabetes by treatment type
      and adherence with healthcare professional advice concerning SMBG. In addition,
      the study aims to investigate the association of SMBG and self-reported episodes
      of low blood glucose. DESIGN AND SETTING: This cross-sectional survey design
      study was carried out on patients with type 2 diabetes aged 18 years or over,
      attending community pharmacies in 97 sites across the United Kingdom. METHODS:
      Patients picking up a prescription for blood glucose test strips or diabetes
      medicine from a community pharmacist were asked to complete a questionnaire. The
      pharmacist was available to assist if requested. Questions included: self-reports
      of frequency of blood glucose testing; type of diabetes treatment; advice given
      by healthcare professionals about frequency of blood glucose testing; frequency
      of episodes of low blood glucose; and last known HbA(1c) level. The final sample
      size was 554 respondents, who were grouped for analysis as follows: those being
      treated with insulin, either alone or with any oral medication (n = 167); those
      being treated with sulfonylureas, either alone or with any oral medication (n =
      187); and those being treated with any other medication, or controlled by diet
      and exercise alone (n = 202). RESULTS: Frequency of SMBG was higher in patients
      using insulin (median 10 times per week, Q (1), Q (3) = 4.5, 14) than in patients
      on treatments other than insulin (four times per week, Q (1), Q (3) = 2, 7, p <
      0.001). SMBG was carried out at the same frequency in patients not treated with
      insulin regardless of whether they were prescribed sulfonylureas. Greater
      frequency of SMBG was associated with self-reports of one or more episodes of low
      blood glucose in the previous six months. CONCLUSIONS: Among patients with type 2
      diabetes, those treated with insulin used SMBG at a greater frequency than those
      not treated with insulin. Increased frequency of testing was associated with
      increased frequency of self-reported episodes of low blood glucose, even among
      patients not taking insulin or sulfonylureas. This raises the possibility that
      episodes of hypoglycaemia may not be accurately identified, leading to
      unnecessary fear, or conversely that treatment is not being adjusted to avoid
      such morbidity. Although further work is needed to explore this association in a
      representative, prospective cohort of patients, possible explanations for reports
      of low-blood glucose should be discussed with patients using SMBG more frequently
      to ensure they are able to accurately identify episodes of hypoglycaemia.

PMID- 18828958
TI  - The relationship between antidepressant and analgesic responses: findings from
      six placebo-controlled trials assessing the efficacy of duloxetine in patients
      with major depressive disorder.
AB  - OBJECTIVE: Debate continues regarding whether onset of analgesia is faster than
      antidepressant effect in antidepressants with both properties. Duloxetine
      hydrochloride (from here on referred to as duloxetine) is effective in both major
      depressive disorder and diabetic peripheral neuropathic pain. This post-hoc
      analysis of six placebo-controlled duloxetine trials in patients with major
      depressive disorder was designed to compare onset of antidepressant activity to
      pain relief. RESEARCH DESIGN AND METHODS: Duloxetine was administered at 40-120
      mg/day versus placebo for up to 9 weeks in outpatient clinic settings. The
      primary depression measure was the HAMD(17) and pain severity was measured using
      visual analog scale (VAS) measuring overall pain, headache, back and shoulder
      pain, and pain while awake. The time course of improvement was profiled using
      repeated measures modeling and Kaplan-Meier product limit estimation. RESULTS: In
      all but one case, significant reductions in HAMD(17) and VAS scores were seen
      within 2 weeks of treatment. Median time to VAS response was consistently shorter
      across all VAS measures than that to HAMD(17) response in both placebo- and
      duloxetine-treated patients with at least modest levels of pain at study entry.
      Regression analyses consistently demonstrated little association between
      analgesic and antidepressant responses. Limitations of these findings include
      that the studies used in these analyses did not require the patients to enroll
      with any specific level of pain. Moreover, the type of pain exhibiting at
      presentation was not routinely identified; therefore, the impact of different
      pain types on these findings is unknown. CONCLUSIONS: Duloxetine's analgesic
      effect is independent of the drug's antidepressant effect. Additionally, faster
      onset of the analgesic effect appears to be a population-specific phenomenon that
      is unmodified in the presence of active agents.

PMID- 18828959
TI  - Assessment of long-term immunological and pulmonary safety of inhaled human
      insulin with up to 24 months of continuous therapy.
AB  - BACKGROUND: This study was performed to characterize the long-term safety and
      efficacy of inhaled human insulin (EXU; Exubera * (insulin human [rDNA origin])
      Inhalation Powder). * Pfizer Inc, New York, NY, USA. SCOPE: Patients with type 1
      or type 2 diabetes (N = 1290) who had successfully completed one of six
      controlled EXU open-label trials elected to receive open-label treatment with EXU
      for up to 3 years, after which they were randomized to discontinue EXU or to
      continue therapy for 6 months, then discontinue. Immunologic safety was assessed
      by insulin antibody (IAb) binding, and pulmonary safety was assessed by tests for
      forced expiratory volume in 1 second (FEV(1)) and carbon monoxide diffusing
      capacity (DL(CO)). In addition, changes over time in IAbs were compared with
      changes in FEV(1), DL(CO), hypoglycemia, and efficacy. FINDINGS: Antibody binding
      increased in patients with either type 1 or type 2 diabetes after initiation of
      EXU and plateaued within 6-12 months (increases were higher in patients with type
      1 diabetes than in patients with type 2 diabetes). Decreases in FEV(1) occurred
      primarily during the first 3-6 months of EXU therapy. Among adult patients in the
      All Subjects set, the mean (+/- SE) annualized rate of decline in FEV(1) was 
      0.053 +/- 0.007 liters/year (95% CI, -0.065, -0.040) in adult patients with type
      1 diabetes, and -0.076 +/- 0.005 liters/year (95% CI, -0.085, -0.067) in patients
      with type 2 diabetes. Changes in DL(CO) occurred primarily during the first 3-6
      months of EXU therapy. Among adult patients, in the All Subjects set, the mean
      (+/- SE) annual decline in DL(CO) was -0.738 +/- 0.097 mL/min/mmHg/year (95% CI, 
      0.927, -0.548) and -0.688 +/- 0.082 mL/min/mmHg/year (95% CI, -0.849, -0.527) in
      patients with type 1 and type 2 diabetes, respectively. Antibody binding did not
      correlate with changes in glycemic control, lung function, dose, or hypoglycemia.
      Following discontinuation of EXU, IAbs decreased to near baseline levels.
      CONCLUSION: These results are consistent with other trials showing long-term
      maintenance of safety and efficacy of EXU despite insulin antibody formation and
      small treatment group differences in pulmonary function. A limitation of the
      study was the lack of a comparator therapy.

PMID- 18828960
TI  - Targeting the pathophysiology of type 2 diabetes: rationale for combination
      therapy with pioglitazone and exenatide.
AB  - OBJECTIVE: The objectives of this article are to review the pathophysiology of
      type 2 diabetes mellitus (T2DM), present the rationale for a pathophysiologically
      based treatment approach for patients with T2DM and discuss the role of the
      therapeutic combination of pioglitazone and exenatide in the management of T2DM.
      METHODS: References were identified from searches of the PubMed database that
      were conducted in May 2007, October 2007 and March 2008 and updates to product
      labeling that occurred between May 2007 and December 2007. Information was
      selected for inclusion on the basis of its relevance to the pathophysiology of
      T2DM or the clinical use of thiazolidinediones or exenatide. Discussion of other
      anti-diabetic treatment strategies is not included. RESULTS: T2DM results from a
      combination of insulin resistance and beta-cell dysfunction. The combination of a
      thiazolidinedione and an incretin mimetic offers a combination of characteristics
      (e.g., glycemic control, reduced insulin resistance, decreased weight, potential
      cardiovascular benefits, beta-cell preservation) that addresses many of the
      pathophysiologic underpinnings of T2DM. A recent small placebo-controlled study
      assessed the effects of exenatide used with a thiazolidinedione (TZD;
      pioglitazone or rosiglitazone) with or without metformin. Exenatide demonstrated
      a greater incidence of glycosylated hemoglobin (HbA(1c)) < 7%; greater reductions
      in fasting blood glucose, postprandial plasma glucose and body weight; and
      improved beta-cell function versus the TZD/placebo group. However, exenatide was
      associated with a high dropout rate, and the 16-week duration of treatment in
      this study precluded evaluation of the long-term effects of the
      exenatide/pioglitazone combination. Furthermore, exenatide/pioglitazone has not
      been compared with any other anti-diabetic combination in a head-to-head clinical
      study. CONCLUSIONS: Dual effects on insulin sensitivity (TZD) and insulin
      secretion (exenatide) make the TZD/exenatide combination a rational treatment
      option for patients who do not attain glycemic control with a single agent.
      Studies undertaken to evaluate the effects on cardiovascular outcomes and the
      potential for prevention of T2DM with impaired glucose tolerance may reveal
      additional advantages of this combination approach.

PMID- 18828961
TI  - Pelvic fasciae in urology.
AB  - INTRODUCTION: Despite the vast literature on pelvic fascia, there is confusion
      over the periprostatic structures and their nomenclature, including their
      orientation, the neurovascular bundles and the existence of the prostatic
      'capsule'. In this review, we seek to clarify some of these issues. MATERIALS AND
      METHODS: Review of published medical literature relating to the anatomy of the
      pelvic fascia including a Pubmed search using the terms - pelvic fascia,
      Denonvilliers' fascia, prostate capsule, neurovascular bundle of Walsh,
      puboprostatic ligament and the detrusor apron. CONCLUSIONS: The findings of the
      study were as follows: 1. The 'capsule' of the prostate does not exist. Rather,
      the fibromuscular band surrounding the prostate forms an integral part of the
      gland. 2. The prostate is surrounded by fascial structures -
      anteriorly/anterolaterally by the prostatic fascia and posteriorly by the
      Denonvilliers' fascia. Laterally, the prostatic fascia merges with the endopelvic
      fascia. 3. The posterior longitudinal fascia of the detrusor comprises a
      'posterior layer' of the detrusor apron, extending from the bladder neck to the
      prostate base. 4. The neurovascular structures tend to be located
      posterolaterally, but may not always form a bundle. A significant proportion of
      fibres may lie away from the main nerve structures, along the lateral/posterior
      aspects of the prostate.

PMID- 18828962
TI  - Dislocation following total hip replacement: the Avon Orthopaedic Centre
      experience.
AB  - INTRODUCTION: The aim of this study was to determine the incidence and outcome of
      dislocation after total hip arthroplasty at our unit. PATIENTS AND METHODS: In
      total, 1727 primary total joint arthroplasties and 305 revision total hip
      arthroplasties were performed between 1993 and 1996 at our unit. We followed up
      1567 (91%) of the primary hip arthroplasties and 284 (93%) of the revision hip
      arthroplasties at 8-11 years after surgery. Patients were traced by postal
      questionnaire, telephone interview or examination of case notes of the deceased.
      RESULTS: The dislocation rates by approach were 23 out of 555 (4.1%) for the
      posterior approach, 0 out of 120 (0%) for the Omega approach and 30 out of 892
      (3.4%) for the modified Hardinge approach. Of dislocations after primary total
      hip arthroplasty, 58.5% were recurrent. The mean number of dislocations per
      patient was 2.81. Overall, 8.1% of revision total hip arthroplasties dislocated.
      70% of these became recurrent. The mean number of dislocations per patient was
      2.87. The vast majority of dislocations occurred within 2 months of surgery.
      DISCUSSION: To our knowledge, this is the largest multisurgeon audit of
      dislocation after total hip arthroplasty published in the UK. The follow-up of 8
      11 years is longer than most comparable studies. The results of this study can be
      used to inform patients as to the risk and outcome of dislocation, as well as to
      the risk of further dislocation.

PMID- 18828963
TI  - Auditing orthopaedic audit.
AB  - INTRODUCTION: Clinical audit plays an important role in the drive to improve the
      quality of patient care and thus forms a cornerstone of clinical governance.
      Assurance that the quality of patient care has improved requires completion of
      the audit cycle. A considerable sum of money and time has been spent establishing
      audit activity in the UK. Failure to close the loop undermines the effectiveness
      of the audit process and wastes resources. PATIENTS AND METHODS: We analysed the
      effectiveness of audit in trauma and orthopaedics at a local hospital by
      comparing audit projects completed over a 6-year period to criteria set out in
      the NHS National Audit and Governance report. RESULTS: Of the 25 audits performed
      since 1999, half were presented to the relevant parties and only 20% completed
      the audit cycle. Only two of these were audits against national standards and 28%
      were not based on any standards at all. Only a third of the audits led by junior
      doctors resulted in implementation of their action plan compared to 75%
      implementation for consultant-led and 67% for nurse-led audits. CONCLUSIONS: A
      remarkably large proportion of audits included in this analysis failed to meet
      accepted criteria for effective audit. Audits completed by junior doctors were
      found to be the least likely to complete the cycle. This may relate to the lack
      of continuity in modern medical training and little incentive to complete the
      cycle. Supervision by permanent medical staff, principally consultants, and
      involvement of the audit department may play the biggest role in improving
      implementation of change.

PMID- 18828964
TI  - Cranial nerve injuries and the retrojugular approach in carotid endarterectomy.
AB  - INTRODUCTION: This is a retrospective case series analysis to compare the
      incidence of cranial nerve injuries in carotid endarterectomy by the retrojugular
      and anteromedial approaches. PATIENTS AND METHODS: Data were extracted from a
      prospectively collected database. Ninety-one retrojugular carotid
      endarterectomies were compared with 145 anteromedial carotid endarterectomies.
      All were performed under local anaesthesia and used the eversion technique. Data
      were analysed using the chi-squared test. RESULTS: Nine (3.8%) cases were
      complicated by cranial nerve injuries. In four cases, multiple nerves were
      involved. In total, 13 (5.5%) cranial nerves were injured. The affected nerves
      were: two (0.8%) marginal mandibular, two (0.8%) laryngeal, three (1.2%)
      accessory and six (2.5%) hypoglossal. There was no statistically significant
      difference in total or specific cranial nerve injuries between the two surgical
      approaches. CONCLUSIONS: The risk of cranial nerve injuries was similar following
      either the retrojugular or anteromedial approach. Accessory nerve injuries were
      only seen in the retrojugular approach but this did not reach statistical
      significance.

PMID- 18828965
TI  - Blue esophagus.

PMID- 18828966
TI  - Mutations in a molecule: the virtues of antagonism.

PMID- 18828967
TI  - Survival trends in patients with gastric and esophageal adenocarcinomas: a
      population-based study.
AB  - OBJECTIVE: To use a population-based approach to describe survival trends in
      patients diagnosed as having gastric or esophageal adenocarcinoma. PATIENTS AND
      METHODS: A population-based complete chart review of all inpatient and outpatient
      records, using the resources of the Rochester Epidemiology Project, was conducted
      in Olmsted County, Minnesota (population 124,277), a primarily rural county with
      one large urban area. All residents of Olmsted County who were diagnosed as
      having gastric or esophageal adenocarcinoma from January 1, 1971, through
      December 31, 2000, were included in the study. The main outcomes were median
      survival and 2-year and 5-year survival rates, by decade of diagnosis. RESULTS:
      From 1971 through 2000, median survival for patients with gastric adenocarcinoma
      (n=121) decreased from 5.5 months to 3.2 months, whereas median survival for
      patients with esophageal adenocarcinoma (n=65) increased from 8.5 months to 11.7
      months. Decade of diagnosis was not significantly associated with patient
      survival for either gastric or esophageal adenocarcinoma (P>.05). There was no
      significant shift in stage of disease at diagnosis during the 30-year period for
      either gastric or esophageal adenocarcinoma (P>.05). CONCLUSION: No significant
      change has occurred in the survival rates of this patient population with gastric
      or esophageal adenocarcinoma, which is representative of the US white population.

PMID- 18828968
TI  - Mortality associated with nephropathy after radiographic contrast exposure.
AB  - OBJECTIVE: To define outcomes from contrast-induced nephropathy (CIN) after both
      intra-arterial and intravenous administration of contrast medium. PATIENTS AND
      METHODS: We performed a retrospective case-matched cohort study at Mayo Clinic's
      site in Rochester, MN, from April 1, 2004, to March 31, 2006. All contrast
      procedures were evaluated for inclusion. Contrast-induced nephropathy was defined
      as creatinine elevation of 25% or more after contrast exposure or of more than
      0.5 mg/dL within 7 days of contrast exposure. Cases of CIN were matched 1:3 with
      controls by age, sex, pre-procedure creatinine elevation, diabetes mellitus, and
      type of imaging procedure. RESULTS: A total of 809 patients who developed CIN
      were matched to 2427 patients who did not develop CIN after contrast exposure. In
      multivariate analyses, CIN was significantly associated with 30-day mortality
      (odds ratio, 3.37; 95% confidence interval [CI], 2.58-4.41; P<.001) and overall
      mortality (hazard ratio, 1.57; 95% CI, 1.32-1.86; P<.001) after adjustment for
      heart failure, hypertension, medications, total hydration, iodine load, prior
      contrast exposure, and all matched variables during the study period. Intravenous
      contrast administration was a risk factor for 30-day mortality (odds ratio, 2.91;
      95% CI, 1.17-7.23; P=.02) and overall mortality (hazard ratio, 3.02; 95% CI, 1.89
      4.82; P<.001) compared with intra-arterial administration of contrast after
      adjustment for heart failure, hypertension, medications, total hydration, iodine
      load, prior contrast exposure, and all matched variables during the study period.
      CONCLUSION: Contrast-induced nephropathy after administration of contrast medium
      is associated with increased mortality. This risk is higher in patients in whom
      contrast medium is administered intravenously than in those in whom it is
      administered intra-arterially.

PMID- 18828969
TI  - Effect of baseline glomerular filtration rate on survival in patients undergoing
      partial or radical nephrectomy for renal cortical tumors.
AB  - OBJECTIVE: To evaluate the effect of baseline renal function and comorbidity
      index on survival in patients with renal tumors. PATIENTS AND METHODS: We
      retrieved demographic, clinicopathologic, body mass index (BMI), and comorbidity
      data (assessed by Charlson-Romano index and hypertension) for 1479 patients who
      underwent partial or radical nephrectomy between January 4, 1995, and June 9,
      2005, for localized renal tumors. We used the abbreviated Modified Diet and Renal
      Disease equation to estimate glomerular filtration rate (eGFR) using the last
      preoperative serum creatinine measurement. Body mass index and eGFR time trends
      were analyzed with linear regression. The effect of BMI, comorbidity, and
      baseline eGFR on disease-free and overall survival was studied using Cox
      regression controlling for pathologic stage, nodal status, and metastasis.
      RESULTS: Over a 10-year interval, median BMI increased from 27 (interquartile
      range [IQR], 24-31) to 28 (IQR, 25-31; P=.004), and median baseline eGFR
      decreased from 70 (IQR, 58-80) to 63 mL/min per 1.73 m(2) (IQR, 57-78; P<.001).
      Multivariate regression demonstrated an association between year of surgery and
      baseline eGFR (P<.001) even after adjusting for age, sex, comorbidity, BMI, and
      tumor size. We repeated the analysis for patients aged 18 to 70 years, and this
      association persisted (P<.001). Baseline eGFR, BMI, and comorbidity were not
      associated with disease-free survival after controlling for stage. However,
      moderately reduced baseline eGFR (45-60 mL/min per 1.73 m(2)) and severely
      reduced eGFR (<45 mL/min per 1.73 m(2)) were significantly associated with
      overall survival (hazard ratio, 1.5; P<.003; and hazard ratio, 2.8; P<.001;
      respectively). CONCLUSION: Baseline eGFR has declined over the past decade.
      Nephron-sparing techniques should be considered for patients with severely
      diminished baseline eGFR.

PMID- 18828970
TI  - Increased left atrial volume index: potent biomarker for first-ever ischemic
      stroke.
AB  - OBJECTIVE: To establish the incidence and correlation of increased left atrial
      volume index (LAVI) in patients with first-ever ischemic stroke. PARTICIPANTS AND
      METHODS: Using our institution's epidemiological database, we defined a cohort of
      432 patients (cases) who underwent transthoracic echocardiography within 60 days
      of first ischemic stroke between January 1, 1985, and December 31, 1994. Left
      atrial volume was measured with the biplane area-length method, indexed to body
      surface area (LAVI, expressed as mL/m(2)). The control group consisted of 416
      community residents who underwent transthoracic echocardiography as participants
      in a stroke risk factor study. Increased LAVI was defined as 28 mL/m(2) or
      higher. Survival in patients was compared with expected survival among white
      Minnesotans and was further modeled as a function of age, sex, LAVI, and clinical
      risk factors. RESULTS: Among the included 306 patients, 230 (75%) had increased
      LAVI (mean+/-SD, 49+/-21 mL/m(2)). Patients with increased LAVI were older than
      those with normal LAVI (mean+/-SD age, 76+/-11 vs 71+/-13 years; P=.003) and had
      more cardiovascular risk factors (mean+/-SD number, 1.8+/-0.07 vs 1.3+/-0.89;
      P<.001). Mean LAVI was higher in cases than in age- and sex-matched controls
      (P<.001). At 5-year follow-up, cases showed excess mortality compared with age
      matched controls (P=.001). After variables were adjusted for age, sex, and
      clinical risk factors, LAVI was independently associated with mortality.
      CONCLUSION: A useful index for prediction of adverse cardiovascular events, LAVI
      might also predict first ischemic stroke and subsequent mortality.

PMID- 18828971
TI  - Development of peripheral opioid antagonists' new insights into opioid effects.
AB  - The recent approval by the US Food and Drug Administration of 2 medications-
      methylnaltrexone and alvimopan--introduces a new class of therapeutic entities to
      clinicians. These peripherally acting mu-opioid receptor antagonists selectively
      reverse opioid actions mediated by receptors outside the central nervous system,
      while preserving centrally mediated analgesia. Methylnaltrexone, administered
      subcutaneously, has been approved in the United States, Europe, and Canada. In
      the United States, it is indicated for the treatment of opioid-induced
      constipation in patients with advanced illness (eg, cancer, AIDS) who are
      receiving palliative care, when response to laxative therapy has not been
      sufficient. Alvimopan, an orally administered medication, has been approved in
      the United States to facilitate recovery of gastrointestinal function after bowel
      resection and primary anastomosis. Clinical and laboratory studies performed
      during the development of these drugs have indicated that peripheral receptors
      mediate other opioid effects, including decreased gastric emptying, nausea and
      vomiting, pruritus, and urinary retention. Laboratory investigations with these
      compounds suggest that opioids affect fundamental cellular processes through
      mechanisms that were previously unknown. These mechanisms include modifications
      of human immunodeficiency virus penetration, tumor angiogenesis, vascular
      permeability, and bacterial virulence.

PMID- 18828972
TI  - Autologous stem cell transplant in 716 patients with multiple myeloma: low
      treatment-related mortality, feasibility of outpatient transplant, and effect of
      a multidisciplinary quality initiative.
AB  - We report on the feasibility of outpatient transplant in 716 patients undergoing
      autologous stem cell transplant for multiple myeloma at Mayo Clinic's site in
      Rochester, MN, from January 1, 2000, through October 31, 2007. We also report on
      the development and effect of a multidisciplinary quality initiative implemented
      by the Mayo Clinic Blood and Marrow Transplant Program involving physicians,
      nurses, pharmacists, dietitians, and financial specialists for outpatient
      management of patients undergoing stem cell transplant. This approach uses an
      electronic ordering system for diagnostic tests and chemotherapy to minimize
      medical errors. Analysis of hospitalization trends since inception of the program
      showed that 278 (39%) of the 716 patients treated completed the transplant
      procedure as outpatients. The median duration of hospitalization for all patients
      was 4 days; age and serum creatinine levels were predictive of the need for and
      duration of hospitalization. We also assessed recent treatment-related mortality
      rates during a 33-month period after implementation of the program (between
      January 1, 2005, and October 1, 2007). The 100-day survival rate was 99.5% for
      patients with low-risk myeloma (transplant during first plateau; n=201) and 97.2%
      for patients with high-risk myeloma (refractory, relapsing or second or greater
      plateau; n=71). The overall 100-day survival rate was 98.9%. Our experience shows
      that outpatient transplant is feasible for all patients with multiple myeloma and
      results in shorter hospital stays and low treatment-related mortality rates.

PMID- 18828973
TI  - Physicians' preferences and attitudes about end-of-life care in patients with an
      implantable cardioverter-defibrillator.
AB  - Clinical guidance is deficient regarding deactivation of implantable cardioverter
      defibrillators (ICDs) in patients with terminal illnesses. We hypothesized that
      many physicians are apprehensive about discussing ICD deactivation with their
      dying patients. Thus, we conducted an anonymous survey of all the physicians in
      the Department of Medicine at Unity Health System in Rochester, NY. The survey
      collected information about the knowledge and preferences of these physicians
      regarding the medical, ethical, and legal issues involved in caring for patients
      with an ICD and terminal illness. Of the 204 surveys distributed, 87 (43%) were
      returned. Among the physicians who responded, 64 (74%) reported experience caring
      for a patient with an ICD and terminal illness. Forty physicians (46%) either
      thought it was illegal or were not sure if it was legal to deactivate an ICD in
      these circumstances. However, if reassured about the legality of discontinuing
      ICD therapy, 79 (91%) of these same respondents said that they would be willing
      to discuss voluntary ICD deactivation with their dying patients. With increased
      knowledge about managing the withdrawal of this potentially life-prolonging
      therapy, physicians are likely to become more skilled at caring for dying
      patients with an ICD.

PMID- 18828974
TI  - Treatment of myeloma: cure vs control.

PMID- 18828975
TI  - Frailty and its potential relevance to cardiovascular care.
AB  - Frailty is characterized by vulnerability to acute stressors and is a consequence
      of decline in overall function and physiologic reserves. An estimated 7% of the
      US population older than 65 years and 30% of octogenarians are frail. The domains
      to define frailty include mobility, strength, balance, motor processing,
      cognition, nutrition, endurance, and physical activity. Pathophysiologic pathways
      leading to frailty involve a multisystem cascade that includes neuroendocrine
      dysfunction with lower insulin-like growth factor and dehydroepiandrosterone
      sulfate and an altered inflammatory milieu with increased levels of C-reactive
      protein, interleukins, tumor necrosis factor alpha, and abnormal coagulation.
      Frailty predicts death and heralds the transition to disability in general
      populations. As the population with coronary artery disease shifts toward older
      patients, physicians must consider the role of frailty in their patients. This
      review will enable clinicians to recognize frailty and consider its relevance in
      their daily practice. We also elaborate on reasons to consider frailty in older
      adults with cardiovascular disease and focus on its early identification, on
      referral to specialists, and on care after serious cardiac events.

PMID- 18828976
TI  - Amebiasis.
AB  - Amebiasis is defined as infection with Entamoeba histolytica, regardless of
      associated symptomatology. In resource-rich nations, this parasitic protozoan is
      seen primarily in travelers to and emigrants from endemic areas. Infections range
      from asymptomatic colonization to amebic colitis and life-threatening abscesses.
      Importantly, disease may occur months to years after exposure. Although E
      histolytica was previously thought to infect 10% of the world's population, 2
      morphologically identical but genetically distinct and apparently nonpathogenic
      Entamoeba species are now recognized as causing most asymptomatic cases. To avoid
      unnecessary and possibly harmful therapies, clinicians should follow the
      diagnostic and treatment guidelines of the World Health Organization.

PMID- 18828977
TI  - 75-year-old man with abdominal pain and weight loss.

PMID- 18828978
TI  - The Massa or Rochester plastic needle.

PMID- 18828979
TI  - Introduction to Symposium on Cardiovascular Diseases.

PMID- 18828980
TI  - Contemporary pacemakers: what the primary care physician needs to know.
AB  - Pacemaker therapy is most commonly initiated because of symptomatic bradycardia,
      usually resulting from sinus node disease. Randomized multicenter trials
      assessing the relative benefits of different pacing modes have made possible an
      evidence-based approach to the treatment of bradyarrhythmias. During the past
      several decades, major advances in technology and in our understanding of cardiac
      pathophysiology have led to the development of new pacing techniques for the
      treatment of heart failure in the absence of bradycardia. Left ventricular or
      biventricular pacing may improve symptoms of heart failure and objective
      measurements of left ventricular systolic dysfunction by resynchronizing cardiac
      contraction. However, emerging clinical data suggest that long-term right
      ventricular apical pacing may have harmful effects. As the complexity of cardiac
      pacing devices continues to grow, physicians need to have a basic understanding
      of device indications, device function, and common problems encountered by
      patients with devices in the medical and home environment.

PMID- 18828981
TI  - Urinary tobacco alkaloid measurement in patients having thromboangiitis
      obliterans.

PMID- 18828982
TI  - Low-dose statin concentration in red yeast rice: a confounding effect on outcome?

PMID- 18828983
TI  - Hysteroscopic sterilization in women with pulmonary vascular disease.

PMID- 18828984
TI  - A quantitative assessment of primary and secondary immune responses in cattle
      using a B cell ELISPOT assay.
AB  - The aim of the study was to build a comprehensive picture of the appearance in
      the blood stream of Ag-specific plasma cells and memory B cells in the bovine
      model. For this purpose, we have developed a method allowing the detection and
      quantification of both cell types within individual calves immunised with
      ovalbumin. During the primary response, we detected a burst of ovalbumin-specific
      plasma cells at days 6 and 7 post-immunisation, which was followed by the
      production of specific Ab, whereas a gradual increase of memory B cells was only
      detected from day 15. As expected, a boost immunisation performed 7 weeks later
      induced a quicker and stronger secondary response. Indeed, a burst of plasma
      cells was detected in the blood at days 3 and 4, which was followed by a strong
      increase in Ab titres. Furthermore, a burst of memory B cells, and not a gradual
      increase, was detected at days 5 and 6 post-boost immunisation. Importantly, we
      showed a strong correlation between the anti-ovalbumin-specific IgG titres
      detected 5 months after secondary immunisation and the plasma cell numbers
      detected in the blood at the peak response after secondary immunisation. The
      detection and quantification of plasma cells following an mmunisation/vaccination
      strategy could constitute a very effective means for predicting the magnitude and
      longevity of an Ab response.

PMID- 18828985
TI  - Faecal shedding, alimentary clearance and intestinal spread of prions in hamsters
      fed with scrapie.
AB  - Shedding of prions via faeces may be involved in the transmission of contagious
      prion diseases. Here, we fed hamsters 10mg of 263K scrapie brain homogenate and
      examined the faecal excretion of disease-associated prion protein (PrP(TSE))
      during the course of infection. The intestinal fate of ingested PrP(TSE) was
      further investigated by monitoring the deposition of the protein in components of
      the gut wall using immunohistochemistry and paraffin-embedded tissue (PET)
      blotting. Western blotting of faecal extracts showed shedding of PrP(TSE) in the
      excrement at 24-72 h post infection (hpi), but not at 0-24 hpi or at later
      preclinical or clinical time points. About 5% of the ingested PrP(TSE) were
      excreted via the faeces. However, the bulk of PrP(TSE) was cleared from the
      alimentary canal, most probably by degradation, while an indiscernible proportion
      of the inoculum triggered intestinal infection. Components of the gut-associated
      lymphoid tissue (GALT) and the enteric nervous system (ENS) showed progressing
      accumulation of PrP(TSE) from 30 days post infection (dpi) and 60 dpi,
      respectively. At the clinical stage of disease, substantial deposits of PrP(TSE)
      were found in the GALT in close vicinity to the intestinal lumen. Despite an
      apparent possibility of shedding from Peyer's patches that may involve the
      follicle-associated epithelium (FAE), only small amounts of PrP(TSE) were
      detected in faeces from clinically infected animals by serial protein misfolding
      cyclic amplification (sPMCA). Although excrement may thus provide a vehicle for
      the release of endogenously formed PrP(TSE), intestinal clearance mechanisms seem
      to partially counteract such a mode of prion dissemination.

PMID- 18828986
TI  - The effect of applying potassium chloride solutions at atmospheric pressure on
      the sensitivity of dentine in man.
AB  - OBJECTIVE: To determine the effects of applying KCl solutions to exposed dentine
      at atmospheric pressure on pain evoked by probing and air blast stimuli in human
      subjects. DESIGN: The experiments were carried out on 24 premolars in 16 subjects
      (aged 16-30 years). A cavity (diameter 3mm, depth 3mm) was cut at the tip of the
      buccal cusp and etched with 35% orthophosphoric acid. The cavity was filled with
      500, 250 mmol/l KCl or 500 mmol/l NaCl for 10 min, after which it was rinsed with
      normal saline. Each solution was tested in 8 teeth. Air blast and probing stimuli
      were applied to the exposed dentine prior to dentine treatment and at 0, 2, 5,
      10, and 20 min after treatment. After each stimulus the subject indicated the
      intensity of the pain evoked on a visual analogue scale (VAS). RESULTS: In teeth
      treated with 250 or 500 mmol/l KCl, the mean VAS response to air blast stimuli
      was significantly decreased at 5 and 10 min after treatment. The mean VAS
      response to probing was significantly decreased 10 min after treatment with 500
      mmol/l KCl. Otherwise there were no significant changes. CONCLUSION: Topical
      application to exposed dentine of solutions containing a high concentration of
      potassium ions at atmospheric pressure produce a temporary reduction in the
      sensitivity of dentine to air blast and probing stimuli.

PMID- 18828987
TI  - Double uteri with cervicovaginal agenesis.
AB  - OBJECTIVE: To report results of managing complex malformation of the genital
      tract and to validate a newer classification (vaginal, cervix, uterus, adnexa
      associated malformation [VCUAM]) for describing such complex anomalies. DESIGN:
      Case report. SETTING: University hospital. PATIENT(S): A patient with complex
      genital malformation. INTERVENTION(S): Laparotomy, double hysterectomy, and
      vaginal reconstruction with use of bilateral neurovascular pudendal thigh flaps.
      Use of VCUAM classification for description of the anatomy of malformation. MAIN
      OUTCOME MEASURE(S): Creation of a neovagina and accurate and complete description
      of the anomaly. RESULT(S): Relief of pelvic pain and creation of patent and
      sensate vagina retaining the innervations of the erogenous zones. The VCUAM
      classification could accurately depict complex anatomic variations.
      CONCLUSION(S): Vaginal reconstruction with use of bilateral neurovascular
      pudendal thigh flaps yields good postoperative results. The VCUAM classification
      reflects anatomic variations in external and internal organs precisely.

PMID- 18828988
TI  - Effect of sludge-fly ash ceramic particles (SFCP) on synthetic wastewater
      treatment in an A/O combined biological aerated filter.
AB  - Novel media-sludge-fly ash ceramic particles (SFCP) employed in an upflow lab
      scale A/O BAF were investigated for synthetic wastewater treatment. The
      influences of hydraulic retention time (HRT), air-liquid ratio (A/L) and
      recirculation on the removals of chemical oxygen demand (CODcr), ammonia
      (NH(4)(+)-N) and total nitrogen (TN) were discussed. The optimum operation
      conditions were obtained as HRT of 2.0 h, A/L of 15:1 and 200% recirculation.
      Under the optimal conditions, 90% CODcr, more than 98% NH(3)-N and approximately
      70% TN were removed. The average consumed volumetric loading rates for CODcr,
      NH(4)(+)-N and TN with 200% recirculation were 4.06, 0.36 and 0.29 kg(m(3)d)(-1),
      respectively. The CODcr and TN removal mainly occurred in the anoxic zone, while
      nitrification was completed at the height of 70 cm from the inlet of the bottom
      due to a suitable column layout of biological aerated filter (BAF). The
      characteristics of wastewater and backwashing affected TN removal to a large
      degree. In addition, the features of media (SFCP) and synthetic wastewater
      contributed to a strong buffer capacity in the BAF system so that the effluent pH
      at different media height fluctuated slightly and was insensitive to
      recirculation.

PMID- 18828989
TI  - Honorary note.

PMID- 18828990
TI  - Is there a pelvic organ prolapse threshold that predicts pelvic floor symptoms?
AB  - OBJECTIVE: The objective of this study was to determine the minimum threshold
      level at which maximum anatomic prolapse predicts bothersome pelvic floor
      symptoms. STUDY DESIGN: We performed a cross-sectional study of women older than
      40 years undergoing gynecologic and urogynecologic examinations using Pelvic
      Organ Prolapse Quantification (POP-Q) examinations to assess support and Pelvic
      Floor Distress Inventory questionnaires to assess symptoms. Across the spectrum
      of prolapse severity, we calculated receiver operating characteristic (ROC)
      curves and areas under the curves (AUCs) for each symptom. RESULTS: Of 296
      participants, age was 56.3 +/- 11.2 years, and 233 (79%) were white. POP-Q stage
      was 0 in 39 (13%), 1 in 136 (46%), 2 in 89 (30%), and 3 in 33 (11%). ROC analysis
      for each symptom revealed an AUC of 0.89 for bulging/protrusion; 0.81 for
      splinting to void; 0.55-0.62 for other prolapse and urinary symptoms; and 0.48
      0.56 for bowel symptoms. Using a threshold of 0.5 cm distal to the hymen, the
      sensitivity (69%) and specificity (97%) were high for protrusion symptoms but
      poor for most other symptoms considered. CONCLUSION: Vaginal descensus 0.5 cm
      distal to the hymen accurately predicts bulging/protrusion symptoms; however, we
      could not identify a threshold of prolapse severity that predicted other pelvic
      floor symptoms.

PMID- 18828991
TI  - [Ossiculoplasty with a partial Spiggle & Theis titanium prosthesis in
      cholesteatoma: functional results].
AB  - OBJECTIVES: To report the functional results of ossicular reconstruction achieved
      with a specific partial prosthesis in tympanoplasty for cholesteatoma. MATERIALS
      AND METHODS: Forty-four patients presenting cholesteatoma of the middle ear were
      involved in a retrospective study. Tympanoplasties were performed by the same
      surgeon over a 30-month period. The patients underwent ossiculoplasty with the
      shortest nondivisible partial titanium Spiggle & Theis prosthesis. Twenty-eight
      procedures were canal wall-up tympanoplasties and 17 were canal wall-down
      procedures; 27 were primary tympanoplasties and 18 were revisions. Audiometric
      data were evaluated before and after surgery, with a mean follow-up of 13.4
      months. RESULTS: Improvement of the air-bone gap was 6+/-12.2dB. The overall
      success rate was 56% and 67% using the Glasgow Benefit Plot and a postoperative
      air-bone gap lower than 20dB, respectively. There was no significant functional
      difference between canal wall-up and canal wall-down procedures. Hearing results
      were better in primary tympanoplasties than in revisions (p=0.004). The extrusion
      rate was 2.2%. CONCLUSION: The functional results observed in this study confirm
      that this partial titanium Spiggle & Theis prosthesis is a valuable biomaterial
      for ossicular reconstruction in primary tympanoplasty for cholesteatoma.

PMID- 18828992
TI  - Emotion regulation in unipolar depression: the effects of acceptance and
      suppression of subjective emotional experience on the intensity and duration of
      sadness and negative affect.
AB  - This study examined the effects of emotional suppression and acceptance in a
      depressed sample. Sixty participants with diagnoses of unipolar depression
      completed a questionnaire packet and participated in an experiment. The
      experiment utilized two conditions to explore correlates of the spontaneous use
      of emotion regulation strategies and the effects of an experimental manipulation
      of acceptance and suppression. Results demonstrated that suppression produced
      short-term reductions in sadness. Notably, anxiety about the experience of
      depressed mood influenced the efficacy of emotional suppression with findings
      showing that suppression was no longer effective at moderate and higher levels of
      anxiety about the experience of depressed mood. Implications of study findings
      for understanding emotion dysregulation in depressive disorders and the treatment
      of depression are discussed.

PMID- 18828993
TI  - Problem-solving training via videoconferencing for family caregivers of persons
      with spinal cord injuries: a randomized controlled trial.
AB  - OBJECTIVE: To examine the effectiveness of an individualized problem-solving
      intervention delivered in videoconferencing sessions with family caregivers of
      persons living with a spinal cord injury (SCI) and possible contagion effects on
      care recipients. DESIGN: Family caregivers were randomly assigned to an education
      only control group or an intervention group in which participants received
      problem-solving training (PST) in monthly videoconference session for a year.
      PARTICIPANTS: Sixty-one caregivers (54 women, 7 men) and their care recipients
      (40 men, 21 women) consented to participate. MAIN OUTCOME MEASURES: The Social
      Problem-Solving Inventory-Revised was administered to caregivers. Caregivers and
      care recipients completed the Inventory to Diagnose Depression, the SF-36 and the
      Satisfaction with Life scale at pre-treatment, 6 months and 12 months. RESULTS:
      Twenty-eight caregivers discontinued the study and their follow-up data were
      unavailable at the final assessment. Older caregivers were more likely than
      younger caregivers to remain in the study. Intent-to-treat analyses projected a
      significant decrease in depression among caregivers receiving PST; efficacy
      analyses indicated this effect was pronounced at the 6th month assessment. ITT
      analyses and efficacy analyses revealed that care recipients of caregivers
      receiving PST reported gains in social functioning over time. CONCLUSIONS:
      Community-based, telehealth interventions may benefit family caregivers and their
      care recipients, but the mechanisms of these effects are unclear. Attrition and
      sample issues should be considered in future studies with these populations.

PMID- 18828994
TI  - Quantitative analysis of EGFR affinity to immobilized glycolipids by surface
      plasmon resonance.
AB  - EGF-induced activation of EGFR tyrosine kinase is known to be inhibited by
      ganglioside GM3, its dimer, and other mimetics. However, details of the
      interaction, such as kinetic properties, have not yet been clarified. The direct
      interaction is now defined by the surface plasmon resonance (SPR) technique. To
      determine the affinity of EGFR for lyso-GM3 or lyso-GM3 mimetic, these glycolipid
      ligands were covalently immobilized onto a sensor chip, and binding affinities
      were investigated. Results of these studies confirmed the direct interaction of
      lyso-GM3 or its mimetic with EGFR. A strong interaction between EGFR and lyso-GM3
      or its mimetic was indicated by increased binding of EGFR to glycolipid
      immobilized surface, in an EGFR dose-dependent manner.

PMID- 18828995
TI  - FeCl3-catalyzed alpha-glycosidation of glycosamine pentaacetates.
AB  - An efficient method for the large-scale preparation of alpha-N
      acetylglycosaminides, such as fluorogenic T(N)-antigen probes and an alpha-GalNAc
      Ser derivative, has been achieved using FeCl(3)-catalyzed one-step condensation
      between commercially available D-glycosamine pentaacetates and fluorogenic
      acceptors (or serine acceptor) in refluxing 1,2-dichloroethane. Experimental
      simplicity, high alpha-stereoselectivity, low cost, satisfactory yield, and the
      environmentally benign nature are major advantages of our approach.

PMID- 18828996
TI  - Engineering of glucoside acceptors for the regioselective synthesis of beta-(1-
      >3)-disaccharides with glycosynthases.
AB  - Glycosynthase mutants obtained from Thermotogamaritima were able to catalyze the
      regioselective synthesis of aryl beta-D-Galp-(1-->3)-beta-D-Glcp and aryl beta-D
      Glcp-(1-->3)-beta-D-Glcp in high yields (up to 90 %) using aryl beta-D-glucosides
      as acceptors. The need for an aglyconic aryl group was rationalized by molecular
      modeling calculations, which have emphasized a high stabilizing interaction of
      this group by stacking with W312 of the enzyme. Unfortunately, the deprotection
      of the aromatic group of the disaccharides was not possible without partial
      hydrolysis of the glycosidic bond. The replacement of aryl groups by benzyl ones
      could offer the opportunity to deprotect the anomeric position under very mild
      conditions. Assuming that benzyl acceptors could preserve the stabilizing
      stacking, benzyl beta-d-glucoside firstly assayed as acceptor resulted in both
      poor yields and poor regioselectivity. Thus, we decided to undertake molecular
      modeling calculations in order to design which suitable substituted benzyl
      acceptors could be used. This study resulted in the choice of 2-biphenylmethyl
      beta-D-glucopyranoside. This choice was validated experimentally, since the
      corresponding beta-(1-->3) disaccharide was obtained in good yields and with a
      high regioselectivity. At the same time, we have shown that phenyl 1-thio-beta-D
      glucopyranoside was also an excellent substrate leading to similar results as
      those obtained with the O-phenyl analogue. The NBS deprotection of the S-phenyl
      group afforded the corresponding disaccharide quantitatively.

PMID- 18828997
TI  - Mechanism of the dehydration of D-fructose to 5-hydroxymethylfurfural in dimethyl
      sulfoxide at 150 degrees C: an NMR study.
AB  - The anomeric composition of d-fructose in dimethyl sulfoxide changes when the
      solution is heated from room temperature to 150 degrees C, with a small increase
      in the alpha-furanose form at the expense of the beta-pyranose tautomer.
      Additionally, a small amount of alpha-pyranose form was also observed at 150
      degrees C. A mechanism is proposed for the dehydration of D-fructose to 5
      hydroxymethylfurfural in DMSO at 150 degrees C, where the solvent acts as the
      catalyst. A key intermediate in the reaction was identified as (4R,5R)-4-hydroxy
      5-hydroxymethyl-4,5-dihydrofuran-2-carbaldehyde by using (1)H and (13)C NMR
      spectra of the sample during the reaction.

PMID- 18828998
TI  - 129/SvJ mice have mutated CD23 and hyper IgE.
AB  - CD23, the low affinity IgE receptor, is hypothesized to function as a negative
      regulator of IgE production. Upon discovering reduced CD23 surface levels in
      129/SvJ inbred mice, we sought to further investigate 129/SvJ CD23 and to examine
      its influence on IgE levels. Five amino acid substitutions were found in 129/SvJ
      CD23. Identical mutations were also observed in CD23 from New Zealand Black and
      129P1/ReJ mice. 129/SvJ B cells proliferated more rapidly than those from BALB/c
      after stimulation with IL-4 and CD40 ligand trimer. However, in vitro IgE levels
      in supernatants from stimulated 129/SvJ B cells were significantly reduced.
      Contrary to the in vitro findings, the 129/SvJ CD23 mutations correlated with a
      hyper IgE phenotype in vivo and 129/SvJ were able to clear Nippostrongylus
      brasiliensis infection more rapidly than either BALB/c or C57BL/6. Overall, this
      study further suggests that CD23 is an important regulatory factor for IgE
      production.

PMID- 18828999
TI  - Sequential local least squares imputation estimating missing value of microarray
      data.
AB  - Missing values in microarray data can significantly affect subsequent analysis,
      thus it is important to estimate these missing values accurately. In this paper,
      a sequential local least squares imputation (SLLSimpute) method is proposed to
      solve this problem. It estimates missing values sequentially from the gene
      containing the fewest missing values and partially utilizes these estimated
      values. In addition, an automatic parameter selection algorithm, which can
      generate an appropriate number of neighboring genes for each target gene, is
      presented for parameter estimation. Experimental results confirmed that
      SLLSimpute method exhibited better estimation ability compared with other
      currently used imputation methods.

PMID- 18829000
TI  - Potential chemoprotective effect of melatonin in cyclophosphamide- and cisplatin
      induced testicular damage in rats.
AB  - OBJECTIVE: To evaluate the effect of melatonin on cyclophosphamide (CP)- and
      cisplatin-induced testicular toxicity with use of sperm parameters and
      biochemical and histopathologic approaches. DESIGN: Experimental study. SETTING:
      Vakif Gureba Hospital, Istanbul, Turkey. ANIMALS: Six-week-old adult male Wistar
      albino rats (N = 48). INTERVENTION(S): Cyclophosphamide was administered to rats
      by gavage at a single dose of 100 mg/kg body weight, only once. Cisplatin was
      injected intraperitoneally at single doses of 7 mg/kg/d for five consecutive
      days. Melatonin was both administered separately and coadministered with CP and
      cisplatin intraperitoneally at a dose of 10 mg/kg body weight. MAIN OUTCOME
      MEASURE(S): Body and testicular weight, epididymal sperm characteristics, plasma
      T, and histopathologic structure of the testicular tissue were determined.
      Malondialdehyde (MDA) and reduced glutathione (GSH) levels and glutathione
      peroxidase (GSH-Px) activity were assessed in testicular tissue. RESULT(S): Body
      and testicular weight, epididymal sperm count, motility and morphology, plasma T
      levels, the activities of GSH-Px, and GSH levels were significantly decreased
      whereas the level of MDA was significantly increased in rats of the CP and
      cisplatin group. Melatonin treatment increased GSH levels and GSH-Px activity,
      decreased MDA level in testicular tissue, and increased plasma T level.
      Cyclophosphamide and cisplatin caused irregular seminiferous tubules, reduction
      of seminiferous epithelial layers, significant maturation arrest, and
      perivascular fibrosis. Melatonin significantly improved histopathologic changes.
      CONCLUSION(S): Melatonin may prevent CP- and cisplatin-induced testicular damage.

PMID- 18829001
TI  - Evaluation of human sperm function after being cryopreserved within the zona
      pellucida.
AB  - OBJECTIVE: To investigate the fertilization ability, chromatin structure, and DNA
      integrity of spermatozoa after being cryopreserved within an empty zona pellucida
      (ZP). DESIGN: Prospective study. SETTING: Reproductive research center in a
      university-affiliated hospital. PATIENT(S): Normozoospermic patients.
      INTERVENTION(S): Spermatozoa were cryopreserved within the ZP or with traditional
      methods. MAIN OUTCOME MEASURE(S): The sperm recovery rate, sperm motility,
      fertilization ability, chromatin structure, and DNA integrity were assessed
      before and after cryopreservation. RESULT(S): Significantly higher sperm recovery
      rate was identified for the spermatozoa cryopreserved within the ZP than those
      cryopreserved with traditional methods, but the motility recovery was similar.
      Frozen-thawed samples showed increased damage to the sperm chromatin and DNA,
      which were assessed by acridine orange test (AO) and terminal deoxynucleotidyl
      transferase-mediated dUDP nick-end labeling assay; however, no difference of
      chromatin and DNA integrity was observed for spermatozoa cryopreserved within the
      ZP or with traditional methods. In addition, the fertilization ability, as
      assessed by injecting spermatozoa into hamster oocytes, was similar for
      spermatozoa cryopreserved with different cryopreservation methods. CONCLUSION(S):
      Cryopreservation of spermatozoa within an empty ZP results in higher sperm
      recovery rate, and the post-thaw sperm functions of spermatozoa cryopreserved
      within the ZP are comparable with spermatozoa cryopreserved with traditional
      methods.

PMID- 18829002
TI  - Prognosis of oocyte donation cycles: a prospective comparison of the in vitro
      fertilization-embryo transfer cycles of recipients who used shared oocytes versus
      those who used altruistic donors.
AB  - OBJECTIVE: To prospectively compare the prognosis of IVF-ET cycles using oocyte
      sharing vs. cycles using altruistic donors. DESIGN: Prospective cohort prognostic
      study. SETTING: University teaching hospital. PATIENT(S): A total of 353
      consecutive infertile women with premature ovarian failure or diminished ovarian
      function. INTERVENTION(S): After receipt of institutional ethics approval, IVF-ET
      was performed with the use of either oocyte sharing (n = 220) or altruistic
      donors (n = 133). Continuous data (mean + SD [95% confidence interval]) were
      compared with Student's t test or Mann-Whitney test as appropriate; categoric
      data were compared with Fisher's exact test, odds ratios (OR), and relative risk
      (RR). Two-tailed P<.05 was considered significant. Logistic regression was used
      to adjust for confounding variables. MAIN OUTCOME MEASURE(S): The primary
      endpoint was clinical pregnancy. The secondary endpoints were E(2) dosage,
      endometrial thickness, fertilization, embryo quality, and rates of embryo
      cleavage, transfer, and implantation, positive beta-hCG, and biochemical,
      ectopic, and multiple pregnancy. RESULT(S): There was no statistically
      significant difference in clinical pregnancy rates (28.18% vs. 30.08%; OR 0.91
      [0.49-1.67]; RR 1.07 [0.69-1.65]; adjusted OR 0.95 [0.51-1.78]). The mean E(2)
      dosage, endometrial thickness, fertilization rate, embryo score, embryo cleavage,
      number of embryos transferred, and rates of implantation, positive beta-hCG, and
      biochemical, ectopic, and multiple pregnancy were similar. CONCLUSION(S): The
      prognosis with use of shared oocytes is similar to that with altruistic donors.

PMID- 18829003
TI  - Role of male factor in early recurrent embryo loss: do antioxidants have any
      effect?
AB  - OBJECTIVE: To evaluate whether increasing antioxidant intake in men with high
      levels of DNA damage or lipid peroxidation improves gestational results in
      couples with history of recurrent embryo loss. DESIGN: Descriptive study (case
      series). SETTING: Early recurrent embryo loss program at the University of
      Antioquia, Medellin, Colombia. PATIENT(S): Seventeen men whose spouses had a
      history of two or more embryo losses before 12 weeks of gestation.
      INTERVENTION(S): Male partners with increased DNA fragmentation index (%DFI) or
      high thiobarbituric acid reactive substances (TBARS) were instructed to consume a
      diet rich in antioxidants or commercial multivitamins containing beta-carotene,
      vitamin C, vitamin E, and zinc for at least 3 months. MAIN OUTCOME MEASURE(S):
      Pregnancy outcome was recorded in the spouses of men with increased %DFI or TBARS
      who received antioxidant supplementation. RESULTS: Of the 17 men, 9 (53%)
      presented with an increased %DFI or TBARS. They were started on an antioxidant
      supplementation regimen. Of these nine men, six of their spouses became pregnant.
      All couples whose male partners accepted antioxidant supplementation achieved a
      successful pregnancy. CONCLUSIONS: Our study demonstrates the benefits of an
      increased intake of antioxidant-rich food or antioxidant supplements by men who
      show high levels of sperm DNA fragmentation or lipid peroxidation, which could
      result in an improvement in gestational outcomes in couples with history of
      recurrent embryo losses.

PMID- 18829004
TI  - Effect of methotrexate exposure on subsequent fertility in women undergoing
      controlled ovarian stimulation.
AB  - OBJECTIVE: To evaluate the pregnancy rate, ovarian responsiveness, and
      endometrial thickness in infertility patients with a history of methotrexate
      exposure who subsequently underwent controlled ovarian stimulation. DESIGN:
      Retrospective cohort study. SETTING: University reproductive endocrinology and
      infertility program. SUBJECT(S): Forty-eight women with infertility undergoing
      ovarian stimulation after receiving methotrexate treatment for ectopic gestation.
      INTERVENTION(S): Methotrexate administration and controlled ovarian stimulation.
      MAIN OUTCOME MEASURE(S): Pregnancy rate, cycle day 3 FSH levels, number of
      oocytes retrieved, and endometrial thickness. RESULT(S): The cumulative
      intrauterine pregnancy rate achieved with controlled ovarian stimulation at 2
      years after methotrexate exposure was 43%, with a mean time to conceive of 181
      days. Thirty-five patients with similar fertility treatments pre- and post
      methotrexate were identified. Within this group, when an IVF cycle occurred
      within 180 days of methotrexate exposure, a significant decline in oocytes
      retrieved was observed. Cycles performed later than 180 days after methotrexate
      exposure did not exhibit a decrease in oocyte production. Endometrial development
      was similar at all time points examined. CONCLUSION(S): These findings suggest a
      time-limited and reversible impact of methotrexate on oocyte yield. If confirmed
      by larger clinical series and/or animal data, these results may impact the
      management of ectopic gestation in the patient with a history of infertility or
      the timing of subsequent treatments.

PMID- 18829005
TI  - Women with spontaneous 46,XX primary ovarian insufficiency (hypergonadotropic
      hypogonadism) have lower perceived social support than control women.
AB  - OBJECTIVE: To test the hypothesis that women with spontaneous primary ovarian
      insufficiency differ from control women with regard to perceived social support
      and to investigate the relationship between perceived social support and self
      esteem. DESIGN: Cross-sectional. SETTING: Mark O. Hatfield Clinical Research
      Center, National Institutes of Health. PATIENT(S): Women diagnosed with
      spontaneous primary ovarian insufficiency (n = 154) at a mean age of 27 years and
      healthy control women (n = 63). INTERVENTION(S): Administration of validated self
      reporting instruments. MAIN OUTCOME MEASURE(S): Personal Resource Questionnaire
      85 and Rosenberg Self-Esteem Scale. RESULT(S): Women with primary ovarian
      insufficiency had significantly lower scores than controls on the perceived
      social support scale and the self-esteem scale. The findings remained significant
      after modeling with multivariate regression for differences in age, marital
      status, and having children. There was a significant positive correlation between
      self-esteem scores and perceived social support in patients. We found no
      significant differences in perceived social support or self-esteem related to
      marital status, whether or not the women had children, or time since diagnosis.
      CONCLUSION(S): This evidence supports the need for prospective controlled
      studies. Strategies to improve social support and self-esteem might provide a
      therapeutic approach to reduce the emotional suffering that accompanies the life
      altering diagnosis of spontaneous primary ovarian insufficiency.

PMID- 18829006
TI  - Role of glutathione S-transferase (GSTM1) gene polymorphism in development of
      uterine fibroids.
AB  - Glutathione S-transferase (GSTM1) plays an important role in the excretion of
      catechol estrogens and is therefore a candidate marker for fibroids. However,
      this case-control study demonstrated no association between GSTM1 polymorphism
      and the risk of leiomyoma in Brazilian women.

PMID- 18829007
TI  - Hyperreactio luteinalis could be a risk factor for development of HELLP syndrome:
      case report.
AB  - OBJECTIVE: To report a unique case of hyperreactio luteinalis in pregnancy
      associated with ovarian torsion and subsequent development of hemolysis, elevated
      liver enzymes, and low platelet count (HELLP) syndrome. DESIGN: Case report.
      SETTING: University medical center. PATIENT(S): A 34-year-old primigravida woman
      with ovarian torsion in 13 weeks of pregnancy and subsequent intrauterine growth
      restriction (IUGR) and HELLP syndrome. INTERVENTION(S): Laparoscopic salpingo
      oophorectomy due to the ovarian torsion and cesarean section (CS) due to the
      development of HELLP syndrome. MAIN OUTCOME MEASURE(S): HELLP syndrome.
      RESULT(S): In the first trimester the patient had symptoms of acute abdomen due
      to the ovarian torsion. Both ovaries were enlarged and multicystic. Hormonal
      studies confirmed an abnormally elevated level of hCG (192.000 IU/L), mild
      hyperthireosis, and hyperandrogenemia. Laparoscopic salpingo-oophorectomy was
      performed. At 30 weeks of pregnancy, IUGR was confirmed sonographically and
      clinically, and at 33 weeks severe preeclampsia developed. One week later, HELLP
      syndrome occurred. Emergency CS was preformed, and she delivered a female newborn
      weighing 1,640 g. Seven days after delivery, blood pressure and hormonal status
      returned to normal. CONCLUSION(S): Hyperreactio luteinalis due to the abnormally
      high level of hCG in the first trimester could be a consequence of inappropriate
      trophoblast invasion and an early sign of subsequently developing preeclampsia,
      eclampsia, and HELLP syndrome.

PMID- 18829008
TI  - Partial recovery of luteal function after bariatric surgery in obese women.
AB  - OBJECTIVE: To determine whether obesity-related reproductive endocrine
      abnormalities in ovulatory women are reversible with weight loss. DESIGN:
      Observational cohort study. SETTING: Healthy volunteers in an academic research
      environment. PATIENT(S): Women aged 18-48 years with regular menstrual cycles 21
      40 days and a body mass index (BMI) >or=35 kg/m(2) planning to undergo bariatric
      surgery were recruited. INTERVENTION(S): Twenty-five eumenorrheic (non-polycystic
      ovary syndrome) women with a mean BMI of 47.3 +/- 5.2 kg/m(2) were sampled with
      daily menstrual cycle urinary hormones before (n = 25) and 6 months after (n = 9)
      weight loss surgery resulting in >25% reduction of initial body weight. Daily
      hormones were compared before and after surgery and with 14 normal-weight control
      subjects. MAIN OUTCOME MEASURE(S): Metabolites of LH, FSH, E(2), and P were
      measured daily for one menstrual cycle. Group means were compared using t tests
      among ovulatory cycles. RESULT(S): Luteal pregnanediol glucuronide (Pdg)
      increased from 32.8 +/- 10.9 to 73.7 +/- 30.5 microg/mg creatinine (Cr) and whole
      cycle LH increased from 168.8 +/- 24.2 to 292.1 +/- 79.6 mIU/mg Cr after
      surgically induced weight loss. Luteal Pdg remained lower than in normal-weight
      control subjects (151.7 +/- 111.1 microg/mg Cr). Obese women took longer to
      attain a postovulatory Pdg rise of >2 microg/mg Cr than control subjects (3.91 +/
      1.51 vs. 1.71 +/- 1.59 days); this improved after surgery (2.4 +/- 1.82 days).
      Whole-cycle estrone conjugates (E(1c)) was similar to control subjects at
      baseline, but decreased after weight loss (from 1,026.7 +/- 194.2 to 605.4 +/-
      167.1 ng/mg Cr). Follicle-stimulating hormone did not relate to body size in this
      sample. CONCLUSION(S): Women of very high BMI have deficient luteal LH and Pdg
      excretion and a delayed ovulatory Pdg rise compared with normal-weight women.
      Although these parameters improved with weight loss, Pdg did not approach levels
      seen in normal-weight women. Luteinizing hormone may be less effective in
      stimulating the corpus luteum in obesity. The large postoperative decrease in
      E(1c) may reflect the loss of estrone-producing adipose tissue after weight loss.

PMID- 18829009
TI  - Preimplantation genetic diagnosis on in vitro fertilization clinic websites:
      presentations of risks, benefits and other information.
AB  - OBJECTIVE: To examine information on preimplantation genetic diagnosis (PGD)
      presented on IVF clinic websites. DESIGN: We systematically sampled every third
      IVF clinic on the 2004 Centers for Disease Control provider list. SETTING: The
      Internet. PATIENT(S): None. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S):
      Benefits, risks, and other types of information mentioned regarding PGD.
      RESULT(S): Of 135 sites examined, 88.1% had websites, and 70% mentioned PGD, of
      which 27% were university- or hospital-based and 63% were private clinics. Sites
      mentioning PGD listed uses and benefits of PGD far more than the risks involved.
      Of these sites, 76% described testing for single-gene diseases, but fewer
      mentioned risks of missing target diagnoses (35%) or risks for loss of embryo
      (18%), and 14% described PGD as new or controversial. Private clinics were more
      likely than other programs to be on either the East or West Coast, list certain
      PGD risks (e.g., diagnostic error), note that PGD was new or controversial,
      reference source of PGD information, provide accuracy rates of genetic testing of
      embryos, and offer gender selection for social reasons. CONCLUSION(S): Most IVF
      clinics advertise PGD online, but the scope and quality of information about it
      varies widely, emphasizing benefits while minimizing risks. Clinics and patients
      may benefit from more thorough and consistent presentation of PGD, drawing on
      available evidence to best provide a realistic portrayal of PGD.

PMID- 18829010
TI  - Point of failure as a predictor of in vitro fertilization treatment
      discontinuation.
AB  - Among 2,245 women, those who experienced a chemical pregnancy that failed to
      progress to a clinically recognized pregnancy or a spontaneous abortion on their
      first IVF cycle were more likely to discontinue IVF treatment than those whose
      first cycle ended before embryo transfer or who did not have a positive pregnancy
      test after transfer. However, among women who did continue to a second IVF cycle,
      those who had at least a chemical pregnancy on the first cycle were more likely
      to have a live birth on the second attempt than those women who had failed before
      conception in the first cycle (34% success rate compared with 21%, respectively).

PMID- 18829011
TI  - Monocyte chemotactic protein-1 (MCP-1), its receptor, and macrophages in the
      perifollicular stroma during the human ovulatory process.
AB  - OBJECTIVE: To evaluate the expression and localization of the macrophage-specific
      chemokine monocyte chemotactic protein-1 (MCP-1), CC chemokine receptor 2 (CCR2),
      and macrophages (CD68) in the perifollicular stroma of different phases of the
      human ovulatory process and its relation to macrophage influx. DESIGN:
      Experimental study on patient-controlled material. SETTING: University hospital.
      PATIENT(S): Twenty-eight women planned to undergo laparoscopic sterilization.
      INTERVENTION(S): Surgery was performed at either of four distinct ovulatory
      phases, and a biopsy sample was obtained from the perifollicular stroma of the
      ovulatory follicle. MAIN OUTCOME MEASURE(S): Real-time polymerase chain reaction,
      immunoblotting, and immunohistochemistry were used for measurements of MCP-1,
      CCR2, and macrophages. RESULT(S): The messenger RNA levels of MCP-1 in the
      perifollicular stroma increased from the preovulatory to the late ovulatory phase
      and declined during the postovulatory phase. A higher density of macrophages was
      found in the preovulatory and early ovulatory phases compared with late and
      postovulatory phases. Monocyte chemotactic protein-1 and CCR2 were present in the
      stroma. Protein expression of CD68 and CCR2 were identified in the four ovulatory
      phases. CONCLUSION(S): This study demonstrates an upregulation of MCP-1 in the
      stroma compartment around the human follicle during the ovulatory process, and a
      high density of macrophages was found at earlier phases. Thus, inflammation-like
      reactions are integral in the ovulatory process and may be targeted to stimulate
      or inhibit this process.

PMID- 18829012
TI  - Fresh testicular sperm retrieved from men with spinal cord injury retains equal
      fecundity to that from men with obstructive azoospermia via intracytoplasmic
      sperm injection.
AB  - OBJECTIVE: To examine the outcomes of intracytoplasmic sperm injection (ICSI)
      with testicular sperm retrieved from men with spinal cord injury. DESIGN:
      Retrospective study. SETTING: Private hospital-based infertility research
      laboratory. PATIENT(S): Twenty-two couples of whom one partner was a man with
      spinal cord injury (SCI). INTERVENTION(S): Reviewing the outcomes of testicular
      sperm extraction (TESE)-ICSI. MAIN OUTCOME MEASURE(S): Testicular sperm retrieval
      rate, fertilization rate, pregnancy rate, comparison with patients with
      obstructive azoospermia. RESULT(S): Testicular sperm were retrieved from 19 of 22
      (86%) patients with SCI. Intracytoplasmic sperm injection resulted in a
      fertilization rate of 236 of 364 (65%). Of 19 couples, 14 couples achieved 18
      pregnancies, and 22 infants (14 singleton and 4 twin) were born. (Pregnancy per
      couple was 74% and that per ICSI was 54%). There was no significant difference in
      pregnancy rate at the first ICSI between SCI couples and obstructive azoospermia
      couples (68% SCI, 68% obstructive azoospermia). However, pregnancy rate per fresh
      testicular sperm-ICSI was significantly higher than that per frozen-thawed sperm
      ICSI in SCI couples (64% SCI fresh, 25% SCI frozen-thawed) although no
      significant difference was seen in obstructive azoospermia couples (76%
      obstructive azoospermia fresh, 63% obstructive azoospermia frozen-thawed). There
      was no significant difference in pregnancy rate between fresh ET cycle and frozen
      thawed ET cycle in SCI couples. CONCLUSION(S): Testicular sperm in men with SCI
      may possess disadvantages in freezing and thawing compared with that in men with
      obstructive azoospermia. Fresh testicular sperm-ICSI may offer optimum outcome
      for SCI couples desirous of pregnancy.

PMID- 18829013
TI  - Challenge in the management of endometriosis in the canal of Nuck.
AB  - OBJECTIVE: To report a case of endometriosis located at an unusual site in the
      canal of Nuck. DESIGN: Case report. SETTING: Department of Obstetrics and
      Gynecology, Chang Gung Memorial Hospital. PATIENT(S): A 35-year-old woman with no
      previous history of surgery had endometriosis in the canal of Nuck excised
      incompletely via an open skin method. Recurrent endometriosis at the canal of
      Nuck was noted 9 months later despite postoperative medical treatment.
      INTERVENTION(S): Laparoscopic surgery and open skin method. MAIN OUTCOME
      MEASURE(S): Removal of endometriosis in the canal of Nuck and repair of the
      inguinal ring. RESULT(S): The patent left canal of Nuck identified, endometriosis
      completely resected, and the inguinal ring closed. She was well 12 months after
      the second surgery. CONCLUSION(S): We suggest that when encountering
      endometriosis in the canal of Nuck, removing all involved lesions and closing of
      the internal inguinal ring is indicated.

PMID- 18829014
TI  - Requirement of leukemia inhibitory factor for establishing and maintaining
      embryonic stem cells in mice.
AB  - OBJECTIVE: To evaluate the necessity of leukemia inhibitory factor (LIF) in
      establishing and self-renewing embryonic stem cells (ESCs). DESIGN: Prospective
      animal model study. SETTING: Gamete and Stem Cell Biotechnology Laboratory, Seoul
      National University, Korea. ANIMAL(S): F1 hybrid B6D2F1 mice. INTERVENTION(S):
      Inner cell mass (ICM) cells of blastocysts were cultured or commercially
      available ESCs were maintained in LIF-free or LIF-containing medium on mouse
      embryonic fibroblast (MEF) feeder. MAIN OUTCOME MEASURE(S): Cell morphology, LIF
      concentration, and mRNA expression. RESULT(S): The MEFs themselves secreted 146.5
      175.3 pg/mL LIF in LIF-free medium. The ICM cells formed ESC-like colonies on MEF
      feeder, and E14 and R1 ESCs were successfully maintained in LIF-free medium.
      Expression of the genes either mediating LIF function or regulating stemness was
      not altered significantly, and change in the growth of ESCs was not prominent in
      LIF-free medium. Neither mRNA expression of differentiation-related genes nor
      differentiation into embryoid body was changed in the ESCs. CONCLUSION(S):
      Addition of LIF to culture medium is not necessary for establishing ICM-derived
      ESC-like colonies in the presence of fibroblast monolayer, and established ESCs
      can be maintained in an LIF-free medium.

PMID- 18829015
TI  - Gonadotropin administration after gonadotropin-releasing-hormone agonist: a
      therapeutic option in severe testiculopathies.
AB  - OBJECTIVE: To evaluate the effect of recombinant human follicle-stimulating
      hormone (FSH) plus human chorionic gonadotropin (hCG) on seminal parameters and
      pregnancy rate in severe testiculopathies after high FSH plasma concentrations
      have been suppressed. DESIGN: Prospective, controlled, randomized clinical study.
      SETTING: Infertility center at a university hospital. PATIENT(S): Eighty-seven
      men affected by severe testiculopathy. INTERVENTION(S): We treated 57 men with a
      gonadotropin-releasing hormone agonist (GnRH-a) and then with recombinant human
      FSH and hCG, and 30 patients did not receive any treatment. Seminal parameters
      and sperm aneuploidies were evaluated during and after the treatment period.
      Couples did not achieve a spontaneous pregnancy received assisted reproduction
      treatment. MAIN OUTCOME MEASURE(S): Seminal parameters, sperm aneuploidies,
      testicular cytologic analysis, FSH, luteinizing hormone, testosterone, inhibin B
      concentrations, and pregnancy rate. RESULT(S): After the therapy period, the
      treated group showed statistically significant improvement in sperm parameters
      and sperm aneuploidies. No changes were observed in the untreated group. A trend
      toward an increase in pregnancy rate also was observed among treated couples
      (cumulative pregnancy rates 31.6% treated vs. 20.0% untreated), although the
      increase was not statistically significant. The improvement of seminal parameters
      in the treated group allowed some patients to undergo in vitro fertilization
      embryo transfer instead of intracytoplasmic sperm injection. CONCLUSION(S):
      Results from this controlled, randomized clinical trial show that FSH therapy
      improves sperm parameters in severe male factor infertility when endogenous high
      FSH plasma levels are suppressed. In cases of severely impaired testicles, a
      rational treatment of male infertility is mandatory to improve the outcome of
      assisted reproduction techniques.

PMID- 18829016
TI  - Does the learning curve of conservative laparoscopic surgery in women with
      rectovaginal endometriosis impair the recurrence rate?
AB  - OBJECTIVE: To assess the effect of surgeon's increasing experience in
      conservative laparoscopic surgery of women with rectovaginal endometriosis on the
      surgical outcome of these patients recurrence rate. DESIGN: Prospective cohort
      study. SETTING: University teaching hospital. PATIENT(S): The first 60
      consecutive patients undergoing laparoscopic conservative surgery for symptomatic
      rectovaginal endometriosis at our institution during a 4- year period.
      INTERVENTION(S): Cases were classified into two groups according to the date of
      the patient's operation: the first 30 cases were defined as the early cases and
      the subsequent 30 cases as the late cases. MAIN OUTCOME MEASURE(S): Operating
      time, perioperative complications, and surgical outcome. Univariate and
      multivariate analyses for risk factors with recurrence of disease. RESULT(S): The
      two groups were similar in patient characteristics. There was a reduction in the
      rate of laparoconversion, operating time, estimated amount of blood loss, cases
      with incomplete removal, and recurrence rate with increasing surgeon's
      experience. Surgical completeness was significantly associated with recurrence of
      disease. CONCLUSION(S): A learning curve is demonstrated in the conservative
      laparoscopic management of patients with rectovaginal endometriosis. After
      gaining experience in performing 30 cases, the recurrence rate is significantly
      reduced.

PMID- 18829017
TI  - Blood ghrelin, resistin, and adiponectin concentrations during the normal
      menstrual cycle.
AB  - OBJECTIVE: To investigate changes of ghrelin, resistin, and adiponectin levels in
      the circulation during the normal menstrual cycle. DESIGN: Longitudinal study.
      SETTING: The study was conducted at a university hospital. PATIENT(S): Eight
      healthy normally cycling women. INTERVENTION(S): The women were observed during a
      whole menstrual cycle. Daily blood samples were taken every morning, after
      overnight fasting, from day 2 of the cycle until the next menstrual period. MAIN
      OUTCOME MEASURE(S): Plasma acylated and unacylated ghrelin and serum resistin,
      adiponectin, FSH, LH, E(2), and P levels were measured in all blood samples.
      RESULT(S): In all women serum FSH, LH, E(2), and P levels, normalized to the
      midcycle peak LH value, showed the typical changes of the normal menstrual cycle.
      Acylated and unacylated ghrelin, resistin, and adiponectin levels did not change
      significantly during the whole menstrual cycle. CONCLUSION(S): The present study
      shows for the first time that plasma ghrelin and serum resistin levels do not
      change significantly during the normal menstrual cycle. It is also confirmed that
      serum adiponectin levels remain stable throughout the cycle. It is suggested that
      ovarian steroid dynamics during the cycle have no effect on the secretion of
      these substances.

PMID- 18829018
TI  - Relationship of progesterone/estradiol ratio on day of hCG administration and
      pregnancy outcomes in high responders undergoing in vitro fertilization.
AB  - OBJECTIVE: To evaluate the predictive value of a serum P/E(2) ratio measured on
      the day of hCG administration regarding pregnancy outcomes in high responders
      undergoing IVF. DESIGN: Retrospective study. SETTING: Teaching hospital.
      PATIENT(S): Two hundred twenty-three infertile women classified as high
      responders in IVF-ET cycles. INTERVENTION(S): Eligible infertile women undergoing
      IVF were assigned to four groups according to serum P levels on the day of hCG
      administration: group 1, P</=0.9 ng/mL; group 2, 0.9 < P<or=1.4 ng/mL; group 3,
      1.4 < P<or=2.0 ng/mL; group 4, P>2.0 ng/mL. The relationship of E(2) level and
      P/E(2) ratio on the day of hCG administration and pregnancy outcomes was
      analyzed. MAIN OUTCOME MEASURE(S): Implantation and pregnancy rate. RESULT(S):
      Patients in group 4 had highest E(2) level and P/E(2) ratio, as well as lowest
      implantation and pregnancy rates. Using P for grouping, the sensitivity/positive
      predictive values (%/%) of P/E(2) ratio in the four groups were 15/66, 30/65,
      30/60, and 25/41, respectively. CONCLUSION(S): Using the level of a single sex
      hormone on hCG day to predict pregnancy outcome in high responders undergoing IVF
      is confounding, whereas using a P/E(2) ratio on hCG day is theoretically
      reasonable. However, the low sensitivity and positive predictive value make the
      use of P/E(2) clinically unfeasible.

PMID- 18829019
TI  - Ability of deoxyribonucleic acid-damaged sperm to withstand freeze-thaw-induced
      damage during cryopreservation.
AB  - OBJECTIVE: To understand the association between sperm DNA damage and the ability
      of DNA-damaged sperm to withstand the freeze-thaw process during
      cryopreservation. DESIGN: Experimental prospective study. SETTING(S): Embryology
      research laboratory. ANIMALS: Eight- to 12-week-old Swiss strain male albino mice
      (Mus musculus). INTERVENTION(S): Sperm carrying a known amount of DNA damage was
      subjected to cryopreservation and thereafter evaluated for survival and freeze
      thaw-induced DNA damage. MAIN OUTCOME MEASURE(S): Elucidation of association
      between the amount of initial sperm DNA damage, cryosurvival, and freeze-thaw
      induced DNA modification. RESULT(S): A strong correlation (R = -0.87) was
      observed between the amount of initial sperm DNA damage and postthaw survival.
      However, no significant enhancement in DNA damage was observed by the
      cryopreservation of spermatozoa with various amounts of DNA damage.
      CONCLUSION(S): Cryopreservation of DNA-damaged sperm does not deteriorate the DNA
      quality, but sperm survival is compromised.

PMID- 18829020
TI  - Two-dimensional HyCoSy with contrast tuned imaging technology and a second
      generation contrast media for the assessment of tubal patency in an infertility
      program.
AB  - OBJECTIVE: To compare the efficiency of hysterosalpingo-contrast-sonography
      performed with air and saline (Hydro-HyCoSy) with HyCoSy performed with contrast
      media (SonoVue) and contrast-tuned imaging technology (CnTI-SonoVue-HyCoSy)
      considering hysterosalpingography (HSG) and laparoscopy (LPS) as reference tests
      and to evaluate the learning curve of this procedure. DESIGN: Retrospective
      study. SETTING: Reproductive unit of a university hospital. PATIENT(S): Forty-two
      infertile female patients. INTERVENTION(S): HyCoSy were performed with a 2.4-mm
      intrauterine catheter. Patients underwent HSG or LPS as controls. MAIN OUTCOME
      MEASURE(S): Mean age, sensitivity, specificity, positive and negative predictive
      value, kappa value, and diagnostic accuracy were evaluated for statistical
      analysis. RESULT(S): Sensitivity, specificity, and positive and negative
      predictive values of Hydro-HyCoSy were 91%, 71%, 55%, and 95%, respectively,
      while for CnTI-SonoVue-HyCoSy they were 87%, 84%, 69%, and 94%. The diagnostic
      accuracy of Hydro-HyCoSy and of CnTI-SonoVue-HyCoSy were 77% and 85%, with a
      Cohen's kappa of 0.52 and 0.66, respectively. CnTI-SonoVue-HyCoSy does not
      require a learning curve period. CONCLUSION(S): CnTI-SonoVue-HyCoSy is more
      accurate than Hydro-HyCoSy for the assessment of fallopian tubes. The very high
      normal predictive value of Hydro-HyCoSy suggests that this procedure could be
      performed as a screening examination, whereas CnTI-SonoVue-HyCoSy could be used
      as a second-step technique.

PMID- 18829021
TI  - Preimplantation aneuploid embryos undergo self-correction in correlation with
      their developmental potential.
AB  - OBJECTIVE: To investigate the incidence of embryos' self-correction during
      preimplantation development in terms of mosaicism and in correlation with its
      developmental stage. DESIGN: Prospective study to compare the chromosome status
      of embryos on day 3 with that of day 5, in correlation with their developmental
      stage. SETTING: In vitro fertilization unit of a university-affiliated hospital.
      PATIENT(S): Eighty-three aneuploid embryos. INTERVENTION(S): Fluorescence in situ
      hybridization (FISH) reanalysis. MAIN OUTCOME MEASURE(S): Day 3 embryos
      classified as mosaic or chromosomally abnormal by preimplantation genetic
      screening (PGS) were reanalyzed on day 5. The results were evaluated in
      correlation with the embryos' developmental stage. RESULT(S): Out of 83 day 3
      aneuploid embryos, 15 (18.1%) were diagnosed with mosaicism. The FISH reanalysis
      on day 5 demonstrated that 27 embryos (32.6%) were partly or entirely normal
      disomic. Of these 83 aneuploid embryos, 8 (9.7%) underwent complete self
      correction. The PGS results demonstrated that 26.5% of the embryos were trisomic,
      of which 41.0% underwent trisomic rescue by day 5. Self-correction was in
      correlation with the embryo's developmental stage, i.e., 38.1% of aneuploid
      embryos that developed to the blastocyst stage underwent self-correction compared
      with only 12.5% of embryos that only cleaved after biopsy. CONCLUSION(S): Our
      results demonstrate that self-correction of aneuploid and mosaic embryos occurs
      probably more significantly during development toward the blastocyst stage than
      in delayed embryos. In addition, trisomic embryos correct themselves more than
      other aneuploidies. These findings suggest that PGS results must be interpreted
      with caution.

PMID- 18829022
TI  - Long-term effects of GnRH agonist, GnRH antagonist, and estrogen plus
      progesterone treatment on apoptosis related genes in rat ovary.
AB  - OBJECTIVE: To define the long-term effects of GnRH antagonist, GnRH agonist, and
      estrogen plus progesterone treatments on apoptosis and apoptosis-related gene
      expressions, including bcl2, bax, and cyt c in rat ovary. DESIGN: Prospective
      placebo-controlled experimental study. SETTING: Obstetrics and Gynecology and
      Medical Biology and Genetics university departments. ANIMAL(S): Forty female
      wistar rats that were 3 to 4 months of age. INTERVENTION(S): Forty rats were
      randomly divided into 4 groups of 10 each. In group 1 (control) each rat received
      normal saline as placebo by gastric lavage. In group 2 (GnRH agonist) 1 mg/kg
      leuprolide acetate in depot form was given for 30 days. In group 3 (GnRH
      antagonist) each animal received 0.1 mg/kg cetrorelix every 2 days. In group 4
      (estrogen plus progesterone) 0.5 mg/kg estradiol valerate and norethisterone
      enantate in depot form was given every 30 days. After 60 days, the animals were
      killed. MAIN OUTCOME MEASURE(S): Assessment of morphology, histology of ovaries,
      determination of the number of apoptotic cells, and analysis of apoptosis-related
      gene expression of bcl2, bax, and cyt c in the rat ovaries. RESULT(S): Long-term
      GnRH antagonist treatment significantly increased bax gene expression, but the
      ratio of bcl2:bax gene expression was constant compared with control group. The
      GnRH agonist treatment significantly increased cyt c gene expression, and
      estrogen plus progesterone treatment significantly decreased bcl 2 and
      significantly increased cyt c expressions. In the estrogen plus progesterone
      group, ovaries were cystic and larger than in the other groups. There was no
      significant morphologic change between the other groups. CONCLUSION(S): Long-term
      administration of GnRH agonist, GnRH antagonist, and estrogen plus progesterone
      can modulate the apoptosis-related genes in rat ovary. Although GnRH antagonist
      treatment does not influence apoptosis, GnRH antagonist and estrogen plus
      progesterone treatments seem to influence apoptosis in rat the ovary. Further
      clinical studies focusing on the effect of these agents on apoptosis-related
      genes could be performed.

PMID- 18829023
TI  - P53 tumor suppressor factor, plasminogen activator inhibitor, and vascular
      endothelial growth factor gene polymorphisms and recurrent implantation failure.
AB  - OBJECTIVE: To examine whether a panel of gene polymorphisms, including p53 codon
      72 tumor suppressor factor, plasminogen activator inhibitor 1 (PAI-1), and
      vascular endothelial growth factor (VEGF) -1154, are risk factors for
      implantation failure after IVF-ET. DESIGN: Case-control study. SETTING: Private
      laboratories and reproduction medical centers. PATIENT(S): Seventy women with
      history of recurrent implantation failure after IVF-ET and 73 fertile control
      women. INTERVENTION(S): Buccal swabs were obtained from all participants. The DNA
      was extracted from the buccal swabs and analyzed for the presence of the PAI
      4G/4G, VEGF -1154A/A, and p53 codon 72 Arg/Pro genotypes. MAIN OUTCOME
      MEASURE(S): The prevalence of homozygous p53 Pro72, PAI 4G/4G, and VEGF -1154A/A
      was compared between women experiencing recurrent implantation failure and
      fertile control women. RESULT(S): The frequencies of homozygous p53 Pro72, PAI
      4G/4G, and VEGF -1154AA were significantly higher among women experiencing
      implantation failure compared with control women. CONCLUSION(S): A panel of tests
      for p53 codon 72 Pro/Pro, PAI-1 4G/4G and VEGF -1154A/A may be useful to identify
      women at risk for implantation failure after IVF-ET.

PMID- 18829024
TI  - Conception and pregnancy outcome in a patient with 11-bp deletion of the
      steroidogenic acute regulatory protein gene.
AB  - OBJECTIVE: To report the pregnancy outcome of a patient with congenital lipoid
      adrenal hyperplasia (CLAH) due to an 11-bp deletion of the steroidogenic acute
      regulatory protein (StAR) gene. DESIGN: Case report. SETTING: University-based
      pediatric endocrinology unit and private IVF clinic. PATIENT(S): A 24-year-old
      woman homozygous for a StAR gene deletion, married to a man heterozygous for the
      same molecular defect. INTERVENTION(S): Ovarian stimulation, oocyte retrieval
      followed by IVF, blastomere biopsy, preimplantation genetic diagnosis, and
      additional estrogen support until placental function initiation. MAIN OUTCOME
      MEASURE(S): Normal pregnancy outcome and delivery of a healthy newborn.
      RESULT(S): A female patient with CLAH gave birth to a normal newborn after IVF
      and preimplantation genetic diagnosis. CONCLUSION(S): Pregnancy is feasible in
      patients with StAR gene mutations, provided that extra estrogens are offered
      until placental function ensues.

PMID- 18829025
TI  - Electrical activation of oocytes after intracytoplasmic sperm injection: a
      controlled randomized study.
AB  - OBJECTIVE: To evaluate the electrical activation of oocytes in patients with
      previously failed or limited fertilization after intracytoplasmic sperm injection
      (ICSI) and in patients with possible failure of fertilization. DESIGN:
      Prospective randomized study. SETTING: A private IVF center in Egypt. PATIENT(S):
      Two hundred forty-six patients with severe oligoasthenospermia or nonobstructive
      azoospermia with total teratospermia or totally immotile spermatozoa were
      selected for the study. Patients who previously had total failure or limited
      fertilization after ICSI also were included. INTERVENTION(S): Sibling oocytes
      were randomly divided after ICSI into two groups: the study group (n = 1,640) was
      subjected to electroactivation, and the control group (n = 1,435), to no
      electroactivation. Electroactivation was performed by using a double-square
      direct-current pulse. Embryo transfer was performed with the best available
      embryos. MAIN OUTCOME MEASURE(S): Fertilization rate, degeneration rate, and
      pregnancy outcome. RESULT(S): Two hundred forty-one ICSI cycles were included in
      the study. The fertilization rate was statistically significantly higher in the
      electroactivated group as compared with in the control group (68% vs 60%, odds
      ratio = 1.397, 95% confidence interval = 1.197 to 1.629). The oocyte degeneration
      rate was not statistically significantly different between the two groups (5.9%
      vs 4.9%, odds ratio = 0.96, 95% confidence interval = 0.73 to 1.26). In total,
      112 clinical pregnancies resulted (pregnancy rate = 46.5%). Total fertilization
      failure occurred in 5 cycles in the control group, and none failed in the study
      group. CONCLUSION(S): Oocyte electroactivation after ICSI significantly improved
      the fertilization rate in severe oligoasthenoteratospermia and nonobstructive
      azoospermia.

PMID- 18829026
TI  - Diminished ovarian reserve in a woman with a balanced 13;21 translocation.
AB  - OBJECTIVE: To present the a case of decreased ovarian reserve in a patient with a
      balanced 13;21 translocation. DESIGN: Case report. SETTING: Reproductive
      endocrinology and infertility practice in a university teaching hospital.
      PATIENT(S): A 33-year-old caucasian woman with primary infertility.
      INTERVENTION(S): Laboratory evaluation, hysterosalpingogram, karyotype analysis,
      semen analysis. MAIN OUTCOME MEASURE(S): Endocrinologic evaluation and genetic
      analysis. RESULT(S): A diagnosis of decreased ovarian reserve based upon
      laboratory evaluation with concomitant findings of a balanced translocation
      between the long arms of chromosomes 13 and 21. CONCLUSION(S): A diagnosis of
      primary infertility secondary to decreased ovarian reserve of unknown etiology,
      but with karyotype evidence of a balanced autosomal translocation and a familial
      history of early menopause, suggested possible roles of autosomal genes in
      mechanisms of ovarian follicular attrition.

PMID- 18829027
TI  - An examination of subgroup classification in irritable bowel syndrome patients
      over time: a prospective study.
AB  - BACKGROUND: Irritable bowel syndrome (IBS) is a complex functional
      gastrointestinal disorder which to date remains poorly understood. Therapies for
      irritable bowel syndrome (IBS) patients are usually aimed at relieving the
      predominant symptom; however, little evidence exists as to whether or not the
      predominant symptom changes with time. Nurses are becoming increasingly involved
      in the assessment and management of IBS patients. OBJECTIVES: To categorise IBS
      patients into one of three sub-types, namely diarrhoea-predominant, constipation
      predominant and a third group who alternate between the two, and to investigate
      changes in patient sub-type classification over time. DESIGN: Observational
      cohort study. SETTING: The general population of the United Kingdom (UK).
      METHODS: A cohort of 494 IBS patients, with a confirmed Rome II classification
      diagnosis, was recruited in the UK. Patients' IBS symptoms were recorded
      throughout a 26-week period. Proportions of individuals in each IBS subgroup were
      calculated and probabilities of moving from one subgroup to another between
      consecutive weeks were estimated. RESULTS: The percentage of patients given an
      overall subgroup classification of diarrhoea-predominant IBD (D-IBS) is 40.9%;
      58.1% and 1% were classified as belonging to the alternator (A-IBS) and
      constipation-predominant (C-IBS) subgroups, respectively. PATIENTS: classified as
      an alternator or as diarrhoea-predominant have a high probability (0.67 and 0.71,
      respectively) of remaining in the same subgroup; however this probability is
      lower for constipation-predominant patients (0.35). CONCLUSION: Although many
      patients remain in the same IBS subgroup classification over time, there are
      individuals whose subgroup classification varies. As such, patients' IBS subgroup
      classification should be reviewed regularly and treatment adjusted accordingly in
      order to optimise patient care.

PMID- 18829028
TI  - Plasma asymmetric dimethylarginine, L-arginine and left ventricular structure and
      function in a community-based sample.
AB  - OBJECTIVE: Increasing evidence indicates that cardiac structure and function are
      modulated by the nitric oxide (NO) system. Elevated plasma concentrations of
      asymmetric dimethylarginine (ADMA; a competitive inhibitor of NO synthase) have
      been reported in patients with end-stage renal disease. It is unclear if
      circulating ADMA and L-arginine levels are related to cardiac structure and
      function in the general population. METHODS: We related plasma ADMA and L
      arginine (the amino acid precursor of NO) to echocardiographic left ventricular
      (LV) mass, left atrial (LA) size and fractional shortening (FS) using
      multivariable linear regression analyses in 1919 Framingham Offspring Study
      participants (mean age 57 years, 58% women). RESULTS: Overall, neither ADMA or L
      arginine, nor their ratio was associated with LV mass, LA size and FS in
      multivariable models (p>0.10 for all). However, we observed effect modification
      by obesity of the relations of ADMA and LA size (p for interaction p=0.04): ADMA
      was positively related to LA size in obese individuals (adjusted-p=0.0004 for
      trend across ADMA quartiles) but not in non-obese people. CONCLUSION: In our
      large community-based sample, plasma ADMA and l-arginine concentrations were not
      related to cardiac structure or function. The observation of positive relations
      of LA size and ADMA in obese individuals warrants confirmation.

PMID- 18829029
TI  - Fasting insulin is a stronger cardiovascular risk factor in women than in men.
AB  - Diabetes is a stronger risk factor for cardiovascular disease (CVD) in women than
      in men. It is not known whether there is also a sex difference in the association
      between hyperinsulinaemia, reflecting insulin resistance, and CVD. Fasting
      insulin was assessed with a specific assay in 6916 fasting, non-diabetic subjects
      of the PREVEND study without a prior history of CVD. Major Adverse Cardiovascular
      Events (MACE) (defined as CVD morbidity and CVD mortality) were prospectively
      recorded after the baseline survey. Cox-regression models were used to
      investigate the association of fasting insulin with subsequent development of
      MACE. Fasting insulin was 54 [38-77]pmol/l in women (age 48+/-12yrs) and 57 [40
      88] pmol/l in men (age 49+/-13yrs). During follow-up for 7.5 [6.9-7.8]yrs, 98
      cardiovascular events were recorded in 3626 women and 242 events in 3290 men.
      There was a significant (P<0.001) interaction between sex and fasting insulin for
      MACE, with the strongest association in women. In women, there was a logarithmic
      association for insulin with MACE, independent of age, alcohol consumption, and
      smoking (HR=1.50 [95% CI 1.17-1.91] per doubling of insulin, P=0.001). In men,
      for a similar multivariate model, there was a logarithmic association (HR=1.13
      [95% CI [0.97-1.32] per doubling of insulin, P=0.1). Further adjustment for
      components of the insulin resistance syndrome weakened the association more in
      men than in women. With HOMA instead of insulin, results were essentially
      similar. In parallel with diabetes, fasting hyperinsulinaemia reflecting insulin
      resistance in non-diabetic subjects is associated with an increased risk for
      cardiovascular disease, which is more pronounced in women than in men.

PMID- 18829030
TI  - Interaction forces and interface properties of KIF1A kinesin-alphabeta tubulin
      complex assessed by molecular dynamics.
AB  - Kinesin is a microtubule-based motor protein that generates motion involved in
      intracellular trafficking and cell division. Even if the force-generating and
      enzymatic properties of kinesin were extensively studied, the molecular basis of
      its interaction with the microtubule is still not well understood. The aim of the
      present study is to provide a detailed description, in terms of conformational
      changes and interaction properties, of the kinesin-alphabeta tubulin complex
      during a cycle of ATP hydrolysis. Four different nucleotide-dependent
      conformations (nucleotide-free, ATP, ADP.Pi and ADP) of the kinesin-alphabeta
      tubulin were constructed and investigated by performing molecular dynamics
      simulations. Computational results show that small conformational changes, in the
      order of few Angstrom, occurring in the kinesin structure reflect on its affinity
      for the filament substrate. Indeed the rotation of the alpha4 helix due to the
      transition from the bound (ADP.Pi) to the unbound (ADP) state, when the Pi is
      released from the complex, coupled with the modification occurred in the loop L9
      of switch I domain are associated to a marked decrease (approximately 45%) of the
      maximum interaction force between the kinesin motor and the tubulin dimer.

PMID- 18829031
TI  - Structural properties of fourth-generation composite femurs and tibias.
AB  - The purpose of this study was to measure the structural properties of the latest
      design (fourth-generation) of composite femurs and tibias from Pacific Research
      Laboratories, Inc. Fourth-generation composite bones have the same geometries as
      the third-generation bones, but the cortical bone analogue material was changed
      to one with increased fracture and fatigue resistance, tensile and compressive
      properties, thermal stability, and moisture resistance. The stiffnesses of the
      femurs and tibias were tested under bending, axial, and torsional loading, and
      the longitudinal strain distribution along the proximal-medial diaphysis of the
      femur was also determined. The fourth-generation composite bones had average
      stiffnesses and strains that were for the most part closer to corresponding
      values measured for natural bones, than was the case for third-generation
      composite bones; all measurements were taken by the same investigator in separate
      studies using identical methodology. For the stiffness tests, variability between
      the specimens was less than 10% for all cases, and setup variability was less
      than 6%.

PMID- 18829032
TI  - Ionic composition of seawaters and derived saline solutions determined by ion
      chromatography and its relation to other water quality parameters.
AB  - Ion chromatography (IC) presents new possibilities for assessing information
      about environmental samples, namely waters of various compositions, ranging from
      high-purity water to highly saline ones. Constant proportion between major ions
      present in seawater, has been assumed in the past, from which the first practical
      equation relating chlorinity and salinity has been developed, being later
      substituted by a practical salinity scale, derived from conductivity measurements
      relative to a standard seawater, according to internationally accepted
      recommended procedures. Seawaters are characterized by salinity values around 35
      while derived saline solutions may present considerable changes in ionic
      composition, conductivity, hence on salinity. Natural and anthropogenic phenomena
      may introduce new issues requiring clarification for which qualitative and
      quantitative information from additional sources is useful, e.g. ionic
      composition from IC. The different ranges of concentration of major and minor
      species present in seawater and derived saline solutions are a challenge for the
      optimization of a practical methodology for composition assessment in two single
      IC runs, one for anions and another one for cations, which has been attained in
      this work. Composition of saline solutions determined by IC was critically
      assessed in terms of anion-cation balance and further related to conductivity and
      salinity measurements aiming to evaluate the quality/completeness of ion
      chromatographic analyses performed at preselected conditions and to search for
      other meaningful relations for efficient recognition/distinction between saline
      solutions of different types.

PMID- 18829033
TI  - Multi-residue method for the analysis of 85 current-use and legacy pesticides in
      bed and suspended sediments.
AB  - A multi-residue method was developed for the simultaneous determination of 85
      current-use and legacy organochlorine pesticides in a single sediment sample.
      After microwave-assisted extraction, clean-up of samples was optimized using gel
      permeation chromatography and either stacked carbon and alumina solid-phase
      extraction cartridges or a deactivated Florisil column. Analytes were determined
      by gas chromatography with ion-trap mass spectrometry and electron capture
      detection. Method detection limits ranged from 0.6 to 8.9 microg/kg dry weight.
      Bed and suspended sediments from a variety of locations were analyzed to validate
      the method and 29 pesticides, including at least 1 from every class, were
      detected.

PMID- 18829034
TI  - Analysis of fumonisins B(1), B(2) and B(3) in corn-based baby food by pressurized
      liquid extraction and liquid chromatography/tandem mass spectrometry.
AB  - A sensitive and reliable method using pressurized liquid extraction (PLE) and
      liquid chromatography (LC)/electrospray ionization (ESI) tandem mass spectrometry
      with a triple quadrupole (QqQ) analyzer has been developed for the analysis of
      fumonisin B(1) (FB(1)), fumonisin B(2) (FB(2)) and fumonisin B(3) (FB(3)) in corn
      based baby foods. Influence of several extraction parameters that affect PLE
      efficiency such as temperature, pressure, solvent extraction, number of cycles
      and dispersant/clean-up agents were studied. The selected PLE operating method
      was: 3g of sample was packed into 11 ml stainless-steel cell and fumonisins were
      extracted with methanol at 40 degrees C, 34 atm in one cycle of 5 min at 60%
      flush. The analytes were ionized in ESI operating with positive ion mode and
      identified by selecting two monitoring transitions, permitting quantification and
      confirmation in a single injection. Recoveries ranged from 68% to 83% at
      fortification levels of 200 microg kg(-1) with relative standard deviation (RSD)
      from 4% to 12%. The limits of quantification were from 2 microg kg(-1) for FB(1)
      and FB(2), and 5 microg kg(-1) for FB(3), which are below the maximum residue
      level established by the European Union legislation in infant formulas. The
      proposed method was successfully applied to the analysis of twenty seven samples
      of baby food products collected from different markets, and one positive sample
      with a content of 15.9 microg kg(-1) for FB(1), 9.2 microg kg(-1)for FB(2) and
      5.8 microg kg(-1) for FB(3) was obtained. Given the simplicity and potential of
      the proposed procedure, its application for safety control is recommended.

PMID- 18829035
TI  - Simultaneous coaxial thermal lens spectroscopy and retro-reflected beam
      interference detection for capillary electrophoresis.
AB  - A novel optical scheme, which accomplished simultaneous coaxial thermal lens
      spectroscopy and retro-reflected beam interference detection for capillary
      electrophoresis, has been described. By a special design, an adjustable pump
      laser waist relative to the probe laser waist was implemented, while some key
      elements for both detection modes were optimized. In either detection modes,
      certain preponderance compared with former reports was indicated. With both
      coaxial thermal lens spectroscopy and retro-reflected beam interference
      detection, the reported detection scheme combined high sensitivity and universal
      property for capillary electrophoresis detection.

PMID- 18829036
TI  - Development and validation of a solid-phase extraction method coupled to liquid
      chromatography with fluorescence detection for the determination of
      fluoroquinolone residues in powdered infant formulae. Application to the analysis
      of samples from the Spanish and Latin American market.
AB  - This paper describes a new method for the effective extraction, clean-up and
      chromatographic analysis of residues of four fluoroquinolones (ciprofloxacin,
      enrofloxacin, danofloxacin and sarafloxacin) in powdered infant formulae and
      follow-on preparations. Samples were reconstituted following the manufacturer's
      recommendations and treated with trichloroacetic acid in methanol 10% (w/v) for
      deproteinization. Two solid-phase extraction cartridges have been evaluated for
      sample clean-up and preconcentration, Strata Screen A and Strata X and the later
      provided the best recoveries for all the analytes tested. Chromatographic
      analysis has been carried out using a polar endcapped column (AQUA C(18)) and
      fluorescence detection, with lomefloxacin (LOME) as internal standard. Method
      validation has been performed according to European Commission Decision
      2002/657/EC criteria, in terms of linearity, recovery, precision, specificity,
      decision limit (CC(alpha)) and detection capability (CC(beta)). Typical
      recoveries ranged between 70 and 110% at levels below and above the maximum
      residue limits of the target analytes in bovine milk, with an excellent intralab
      reproducibility (RSDs<7%). Matrix effects did not significantly affect method
      accuracy, as evidenced by analyzing different brands of milk. The method has been
      successfully applied to the analysis of 100 samples of infant and follow-on
      formulae of the Spanish and Latin American market, using LC-MS/MS as confirmatory
      technique.

PMID- 18829037
TI  - Simultaneous sampling and analysis for vapor mercury in ambient air using needle
      trap coupled with gas chromatography-mass spectrometry.
AB  - A needle trap (NT) technique for simultaneous sampling and analysis of vapor and
      particle mercury in ambient air using gold wire filled in a syringe needle has
      been developed. This NT technique relies on gold amalgamation rather than
      adsorption/absorption to traditional solid-phase microextraction. Hg trapped by
      Au-amalgamation NT is thermally desorbed in a hot injection port of a gas
      chromatograph; desorbed Hg is then determined by the coupled mass spectrometer.
      This simultaneous sampling and analysis technique were optimized, tested, and
      used for the collection and accurate determination of elemental Hg in ambient
      air. Linear calibration curves were obtained for Hg sampling by NT when mass
      spectrometry (MS) was used for detection; they spanned over 4 orders of
      magnitude. MS offered excellent sensitivity and selectivity. Selected ion monitor
      (SIM) mode was used for the linear calibration curves. The selected quantitation
      ion was m/z 202, since m/z 202 was the strongest isotope of mercury mass
      spectrum. The method was verified with HgCl(2) spiked solution samples. An
      excellent agreement was found between the results obtained for the Hg-saturated
      air samples and HgCl(2) spiked solution samples. The use of the Au-amalgamation
      gas-sampling needle trap method, for the measurement of Hg in air and Hg(2+)
      water samples, is described herein.

PMID- 18829038
TI  - A small-angle X-ray scattering study of the structure of lysozyme-sodium dodecyl
      sulfate complexes.
AB  - The structure of lysozyme-sodium dodecyl sulfate (SDS) complexes in solution is
      studied using small-angle X-ray scattering (SAXS). The SAXS data cannot be
      explained by the necklace and bead model for unfolded polypeptide chain
      interspersed with surfactant micelles. For the protein and surfactant
      concentrations used in the study, there is only marginal growth of SDS micelles
      as they complex with the protein. Being a small and rather rigid protein,
      lysozyme can penetrate the micellar core which is occupied by flexible and
      disordered paraffin chains and also the shell occupied by the hydrated head
      groups. A partially embedded swollen micellar model seems appropriate and
      describes well the scattering data. The SAXS intensity profiles are analyzed by
      considering the change in the electron scattering length density of the micellar
      core and shell due to complexation with protein and treating the intermicellar
      interaction using rescaled mean spherical approximation (RMSA) for charged
      spheres.

PMID- 18829039
TI  - Adsorption of cellulose derivatives on flat gold surfaces and on spherical gold
      particles.
AB  - The adsorption of hydroxyethylcellulose (HEC), ethyl(hydroxyethyl)cellulose
      (EHEC), and their hydrophobically modified counterparts HM-HEC and HM-EHEC has
      been studied on planar gold and citrate-covered gold surfaces by means of quartz
      crystal microbalance with dissipation monitoring (QCM-D), and on citrate-covered
      gold particles with the aid of dynamic light scattering (DLS). The QCM-D results
      indicate that larger amounts of polymer are adsorbed from aqueous solutions of HM
      HEC and HM-EHEC on both substrates than from solutions of their unmodified
      analogues. The adsorption affinity for all the polymers, except EHEC, is higher
      on the citrate-covered surfaces than on the bare gold substrate. This indicates
      that more adsorption sites are activated in the presence of the citrate layer.
      The experimental adsorption data for all the polymers can be described fairly
      well by the Langmuir adsorption isotherm. However, at very low polymer
      concentrations significant deviations from the model are observed. The value of
      the hydrodynamic thickness of the adsorbed polymer layer (delta h), determined
      from DLS, rises with increasing polymer concentration for all the cellulose
      derivatives; a Langmuir type of isotherm can be used to roughly describe the
      adsorption behavior. Because of good solvent conditions for HEC the chains extend
      far out in the bulk at higher concentrations and the value of delta h is much
      higher than that of HM-HEC. The adsorption of EHEC and HM-EHEC onto gold
      particles discloses that the values of delta h are considerably higher for the
      hydrophobically modified cellulose derivative, and this finding is compatible
      with the trend in layer thickness estimated from the QCM-D measurements.

PMID- 18829040
TI  - Synthesis of 3D pore mesostructured silica films by vapor infiltration of
      tetraethoxysilane.
AB  - Nonionic alkyl poly(oxyethylene) surfactants (Brij 56) films on a silicon
      substrate were treated with a tetraethoxysilane (TEOS) vapor. Mesostructured
      silica films were formed through a nano-phase transition under the infiltration
      of TEOS into the surfactant films. It was found that the calcined film had a 3D
      pore structure from the field emission scanning electron microscope (FE-SEM)
      observations in a different orientation. Grazing angle of incidence small angle X
      ray scattering (GISAXS) measurement results showed that the symmetry of the film
      was an Fmmm space group oriented with the (010) plane parallel to the surface.
      The ordered structure of the films showed higher thermal stability than the films
      prepared by a conventional solvent-evaporation method.

PMID- 18829041
TI  - A study of sodium silicate in aqueous solution and sorbed by synthetic magnetite
      using in situ ATR-FTIR spectroscopy.
AB  - The sorption of sodium silicate by synthetic magnetite (Fe3O4) at different pH
      conditions (pH 7-11) and initial silicate concentrations (1 x 10(-3) and 10 x 10(
      3) molL(-1)) was studied using in situ attenuated total reflection Fourier
      transform infrared (ATR-FTIR) spectroscopy. The analysis of infrared spectra of
      sodium silicate in solution as well as adsorbed on magnetite nano-particles
      clearly showed the evolution of different silicate species depending on pH and
      silica concentration. The silicate concentration studied (10 x 10(-3) molL(-1))
      contained polymeric or condensed silicate species at lower pH as well as monomers
      at high pH, as evident from infrared spectra. Condensation of monomers resulted
      in an increased intensity of absorptions in the high frequency part (>1050 cm(
      1)) of the spectral region, which contains information about both silicate in
      solution and sorbed silicate viz. 1300 cm(-1)-850 cm(-1). In the pH range
      studied, infrared spectra of sorbed silicate and sorbed silicate during
      desorption both indicated the presence of different types of surface complexes at
      the magnetite surface. The sorption mechanism proposed is in accordance with a
      ligand exchange reaction where both monodentate and bidentate complexes could
      exist at low surface loading level, the relative proportion of the complexes
      being due to both pH and concentration in solution. Oligomerization occurred on
      the magnetite surface at higher surface loading.

PMID- 18829042
TI  - Chemical modification of carbon black by a simple non-liquid-phase approach.
AB  - Chemical modification is the most popular and efficacious approach to improve
      dispersion stability for commercial carbon blacks in organic media. Even though
      this method has been used successfully in liquid systems, there have been few
      reports of chemical modification of carbon black in non-liquid-phase systems. In
      the present work, a simple non-liquid-phase approach to preparing modified carbon
      black with high dispersibility and stability in polar organic media from an
      industrial carbon black, N220, is reported. The treatment was carried out in a
      rheology mixer by blending carbon black with a low-molecular-weight organic
      compound, 3,9-bis-(1,1-dimethyl-2[beta-(3-tert-butyl-4-hydroxy-5
      methylphenyl)propionyloxy]ethyl)-2,4,8,10-tetraoxaspiro[5,5]-undecane (AO-80),
      under proper conditions. The modified carbon black had a smaller particle size
      than the original carbon black, as proven by dynamic light scattering and
      transmission electron microscopy, and it could be dispersed facilely in acetone
      to form a stable suspension. Time-of-flight secondary ion mass spectroscopy was
      used to detect the chemical presence of AO-80 fragments on the surface of the
      modified carbon black and consequently the modification mechanism.

PMID- 18829043
TI  - Cleaning using nanobubbles: defouling by electrochemical generation of bubbles.
AB  - Here we demonstrate that nanobubbles can be used as cleaning agents both for the
      prevention of surface fouling and for defouling surfaces. In particular
      nanobubbles can be used to remove proteins that are already adsorbed to a
      surface, as well as for the prevention of nonspecific adsorption of proteins.
      Nanobubbles were produced on highly oriented pyrolytic graphite (HOPG) surfaces
      electrochemically and observed by atomic force microscopy (AFM). Nanobubbles
      produced by electrochemical treatment for 20 s before exposure to bovine serum
      albumin (BSA) were found to decrease protein coverage by 26-34%. Further, pre
      adsorbed protein on a HOPG surface was also removed by formation of
      electrochemically produced nanobubbles. In AFM images, the coverage of BSA was
      found to decrease from 100% to 82% after 50 s of electrochemical treatment. The
      defouling effect of nanobubbles was also investigated using radioactively labeled
      BSA. The amount of BSA remaining on a stainless steel surface decreased by
      approximately 20% following 3 min of electrochemical treatment and further cycles
      of treatment effectively removed more BSA from the surface. In situ observations
      indicate that the air-water interface of the nanobubble is responsible for the
      defouling action of nanobubbles.

PMID- 18829044
TI  - A small molecular size system giving unexpected surface effects: alpha
      Cyclodextrin + sodium dodecyl sulfate in water.
AB  - Maximum drop volumes (MDV) and the resultant surface tension values (sigma) of
      alpha-cyclodextrin (alpha-CD) + sodium dodecyl sulfate (SDS) aqueous mixtures
      have been determined over a broad concentration range of both solutes at 283.15,
      293.15, 303.15, 313.15, and 323.15 K. Drops significantly larger than those of
      pure water (up to approximately 25% larger) were observed at low temperatures for
      solutions with [alpha-CD]/[SDS] concentration ratios, approximately > 2,
      producing unexpectedly high surface tension values. Our results indicate that at
      certain solute concentration ratios and temperatures, the drop volume method
      provides wrong values for equilibrium surface tensions. This is due to the high
      viscoelasticity of the surface film whose effect is important even though the
      injection rate of the drops was slow and the solutes molecular sizes are small.

PMID- 18829045
TI  - Influence of specific surface area of pyrogenic silicas on their heat of
      immersion in water and on their surface properties assessed using inverse gas
      chromatography.
AB  - The heat of immersion and the surface properties of pyrogenic silicas were
      examined using microcalorimetry and inverse gas chromatography at finite
      concentration (FC-IGC). The microcalorimetric measurements showed a regular
      decrease of the heat of immersion, in water, per area unit with an increase in
      the surface areas. The desorption isotherms were established using FC-IGC. It is
      observed that BET constant value goes through a minimum, whereas the shapes of
      distribution function of the adsorption energies of isopropanol are changing. All
      results could be interpreted using a model of formation of the pyrogenic silica
      in the flame, which explains the change of surface functionality and geometry
      occurring around 200 m2/g.

PMID- 18829046
TI  - Distribution and structural behavior of hemoglobin between the two phases in
      SDS/n-C5H11OH/H2O system.
AB  - In the sodium dodecyl sulfate (SDS)/n-pentanol (n-C5H11OH)/water (H2O) system, LL
      is the coexisting region of W/O and O/W or bicontinuous microemulsions. In the LL
      region, the system separates into two phases (the upper phase and the lower
      phase) spontaneously. The distribution and structural behavior of hemoglobin (Hb)
      between the upper and lower phases in SDS/n-C5H11OH/H2O system were studied by UV
      vis and circular dichroism (CD) spectroscopy. The results indicate that different
      structures of the two phases bring the conformational change of Hb. The addition
      of Hb results in the redistribution of SDS between the upper and lower phases.

PMID- 18829047
TI  - Molecular dynamic simulation of platinum heater and associated nano-scale liquid
      argon film evaporation and colloidal adsorption characteristics.
AB  - A novel 'fluid-wall thermal equilibrium model' for the wall-fluid heat transfer
      boundary condition has been developed in this paper to capture the nano-scale
      physics of transient phase transition of a thin liquid argon film on a heated
      platinum surface and the eventual colloidal adsorption phenomenon as the
      evaporation is diminishing using molecular dynamics. The objective of this work
      is to provide microscopic characterizations of the dynamic thermal energy
      transport mechanisms during the liquid film evaporation and also the resulting
      non-evaporable colloidal adsorbed liquid layer at the end of the evaporation
      process. A nanochannel is constructed of platinum (Pt) wall atoms with argon as
      the working fluid. The proposed model is validated by heating liquid argon
      between two Pt walls and comparing the thermal conductivity and change in
      internal energy to thermodynamic properties of argon. Later on, phase change
      process is studied by simulating evaporation of a thin liquid argon film on a Pt
      wall using the proposed model. Gradual evaporation of the liquid film occurs
      although the film does not vaporize completely. An ultra-thin layer of liquid
      argon is noticed to have "adsorbed" on the platinum surface. An analysis similar
      to the theoretical study by Hamaker (1937) is performed for the non-evaporating
      film and the value of the Hamaker-type constant falls in the typical range. This
      analysis is done to quantify the non-evaporating film with an attempt to use
      molecular dynamics simulation results in continuum mechanics.

PMID- 18829048
TI  - The tuned-morphology studies of the complexes between poly(N-isopropylacrylamide)
      b-poly(vinylpyridine) and poly(N-isopropylacrylamide-co-hydroxylethyl
      methacrylate)-b-poly(vinylphenol).
AB  - Poly(N-isopropylacrylamide)-b-poly(vinylpyridine) (PNIPAAm-b-PVP) and poly(N
      isopropylacrylamide-co-hydroxylethyl methacrylate)-b-poly(vinylphenol) (P(NIPAAm
      co-HEMA)-b-PVPhol) were synthesized by reversible addition-fragmentation chain
      transfer (RAFT) polymerization. Above two copolymers could form complex in pure
      water and in DMF/water environment with the DMF content lower than 40% by
      hydrogen bondings. The morphologies of the complex were investigated by
      transmission electron microscope (TEM). It was found that the dimension of the
      complex in strong acid (pH 1.0) or base environment (pH 12.0) was smaller than
      the one in weak acid or in neutral environment. After the shell cross-linking of
      the complex, the complex showed a type of "swollen" state in acid or base
      environment which is similar to the properties of microgel.

PMID- 18829049
TI  - Developmental shifts in children's sensitivity to visual speech: a new multimodal
      picture-word task.
AB  - This research developed a multimodal picture-word task for assessing the
      influence of visual speech on phonological processing by 100 children between 4
      and 14 years of age. We assessed how manipulation of seemingly to-be-ignored
      auditory (A) and audiovisual (AV) phonological distractors affected picture
      naming without participants consciously trying to respond to the manipulation.
      Results varied in complex ways as a function of age and type and modality of
      distractors. Results for congruent AV distractors yielded an inverted U-shaped
      function with a significant influence of visual speech in 4-year-olds and 10- to
      14-year-olds but not in 5- to 9-year-olds. In concert with dynamic systems
      theory, we proposed that the temporary loss of sensitivity to visual speech was
      reflecting reorganization of relevant knowledge and processing subsystems,
      particularly phonology. We speculated that reorganization may be associated with
      (a) formal literacy instruction and (b) developmental changes in multimodal
      processing and auditory perceptual, linguistic, and cognitive skills.

PMID- 18829050
TI  - Antiemetic medications in children with presumed infectious gastroenteritis-
      pharmacoepidemiology in Europe and Northern America.
AB  - OBJECTIVE: To investigate the prescription pattern of antiemetic medications in 0
      to 9-year-old children with infectious gastroenteritis in several industrialized
      countries during 2005. STUDY DESIGN: We retrospectively retrieved data from 4
      national and international databases (IMS MIDAS, IMS disease analyzer, WIdO
      databases). RESULTS: Between 2% and 23% of children with gastroenteritis
      (International Classification of Diseases code A08.X or A09) received
      prescriptions for antiemetic medications (United States, 23%; 95% CI, 15-31;
      Germany, 17%; 95% CI, 15-20; France, 17%; 95% CI, 14-19; Spain, 15%; 95% CI, 10
      19; Italy, 11%; 95% CI, 7-16; Canada, 3%; 95% CI, 0-16; United Kingdom, 2%; 95%
      CI, 1-2). The antihistamines dimenhydrinate and diphenhydramine were most
      frequently used in Germany and Canada, whereas promethazine was prescribed
      preferentially in the United States. In France, Spain, and Italy, the dopamine
      receptor antagonist domperidone was preferred as antiemetic treatment.
      Ondansetron was used in a minor proportion of antiemetic prescriptions (Germany,
      Canada, Spain, and Italy, 0%; United States, 3%; United Kingdom, 6%). CONCLUSION:
      Antiemetic drugs are frequently used in children with gastroenteritis. In
      different industrialized countries, prescription of antiemetic medication varies
      considerably. Ondansetron, the only drug with evidence-based antiemetic efficacy,
      plays a minor role among antiemetic prescriptions.

PMID- 18829051
TI  - Five new consanguineous families with horizontal gaze palsy and progressive
      scoliosis and novel ROBO3 mutations.
AB  - Horizontal gaze palsy and progressive scoliosis (HGPPS) is an autosomal recessive
      neurologic disorder caused by homozygous or compound heterozygous mutations in
      the ROBO3 gene on chromosome 11. We clinically evaluated seven individuals with
      HGPPS from five previously unreported consanguineous families. We sequenced ROBO3
      in all affected individuals, additional unaffected members of each family, and
      ethnic controls. All affected individuals had severe horizontal gaze restriction,
      progressive scoliosis, and lower brainstem hypoplasia on neuroimaging, the
      hallmarks of this syndrome. One individual experienced head trauma with a right
      subdural hematoma associated with a right hemiparesis, observations that confirm
      clinically for the first time that corticospinal tracts in HGPPS are uncrossed.
      We found five novel homozygous ROBO3 mutations (four missense mutations and one
      base deletion) distributed throughout the extracellular domain of the gene. The
      ROBO3 gene does not appear to have an obvious hot spot area for mutations;
      therefore, we recommend sequencing all exons and exon-intron boundaries in
      patients with clinical and/or radiologic features of HGPPS.

PMID- 18829052
TI  - Management of coral reefs: we have gone wrong when neglecting active reef
      restoration.
AB  - The current best management tools employed in coral reefs worldwide do not
      achieve conservation objectives as coral reefs continue to degrade. Even improved
      reef management helps, at best, to reduce the degradation pace, whereas the
      worsening global changes foretell a dismal fate for coral reefs. The assertion
      made here is that the prospect for reefs' future is centered on omnipresent
      acceptance of restoration, an 'active' management instrument. A recent promising
      such tool is the 'gardening concept', influenced by the well-established
      scientific discipline of terrestrial forestation. This notion is supported by a
      two-step protocol. The first step entails rearing coral "seedlings", in specially
      designed underwater nurseries, to transplantable size, before applying the second
      step, out-planting into damaged areas of the nursery-farmed coral colonies. Only
      the establishment of large-scale nurseries and transplantation actions, together
      with conventional management tools, will be able to cope with extensive reef
      degradation on the global scale.

PMID- 18829053
TI  - Inhibition of pectin methyl esterase activity by green tea catechins.
AB  - Pectin methyl esterases (PMEs) and their endogenous inhibitors are involved in
      the regulation of many processes in plant physiology, ranging from tissue growth
      and fruit ripening to parasitic plant haustorial formation and host invasion.
      Thus, control of PME activity is critical for enhancing our understanding of
      plant physiological processes and regulation. Here, we report on the
      identification of epigallocatechin gallate (EGCG), a green tea component, as a
      natural inhibitor for pectin methyl esterases. In a gel assay for PME activity,
      EGCG blocked esterase activity of pure PME as well as PME extracts from citrus
      and from parasitic plants. Fluorometric tests were used to determine the IC50 for
      a synthetic substrate. Molecular docking analysis of PME and EGCG suggests close
      interaction of EGCG with the catalytic cleft of PME. Inhibition of PME by the
      green tea compound, EGCG, provides the means to study the diverse roles of PMEs
      in cell wall metabolism and plant development. In addition, this study introduces
      the use of EGCG as natural product to be used in the food industry and
      agriculture.

PMID- 18829054
TI  - [Ethnic rhinoplasty, treatment modalities].

PMID- 18829055
TI  - [Nocardia brain abscess: features, therapeutic strategies and outcome].
AB  - BACKGROUND AND PURPOSE: Nocardia species is an aerobic soil-saprophyte bacterium,
      responsible for rare opportunistic infections, mainly reported in
      immunocompromised patients. Nocardia brain abscess accounts for 1 to 2% of
      cerebral abscesses. Prognosis is poor. METHODS: We describe clinical,
      radiological and bacteriological findings along with therapeutic aspects for five
      patients and review the literature on Nocardia cerebral abscess. RESULTS: The
      clinical features of Nocardia brain abscess are insidious and nonspecific,
      occurring frequently with a medical background of obvious or latent
      immunodeficiency; fever, if any, is observed subordinate to extracerebral
      nocardiosis. Computerized tomography scan and conventional magnetic resonance
      (MR) scan show lesions with a necrotic core and multilobed thick walls enhancing
      after injection of gadolinium or iodine. Abscesses are mainly located in the
      brain stem, basal ganglia and cerebral cortex of the frontal, parietal and
      occipital lobes; cerebellar and spinal locations are uncommon. MR diffusion
      weighted imaging with calculation of apparent diffusion coefficient and proton MR
      spectroscopy can provide additional data for accurate differential diagnosis
      between abscess and other necrotic lesions, such as tumor and cyst formations.
      Bacteriological identification has progressed with advances in molecular
      microbiology: 16S rRNA sequencing, allowing a more rapid routine identification
      of Nocardia strains from clinical samples. Clinical management of patients with a
      Nocardia brain abscess relies upon early use of intravenous antibiotics adapted
      to the strains identified and their susceptibility. Most Nocardia strains display
      susceptibility to cotrimoxazol, amikacin and linezolid, but develop beta
      lactamase activity. CONCLUSIONS: Early pus samples, obtained by biopsy or
      surgical resection, are needed to establish a certain bacteriological diagnosis
      and initiate appropriate intravenous antibiotics.

PMID- 18829056
TI  - Evidence of multiple pyrethroid resistance mechanisms in the malaria vector
      Anopheles gambiae sensu stricto from Nigeria.
AB  - Pyrethroid insecticide resistance in Anopheles gambiae sensu stricto is a major
      concern to malaria vector control programmes. Resistance is mainly due to target
      site insensitivity arising from a single point mutation, often referred to as
      knockdown resistance (kdr). Metabolic-based resistance mechanisms have also been
      implicated in pyrethroid resistance in East Africa and are currently being
      investigated in West Africa. Here we report the co-occurrence of both resistance
      mechanisms in a population of An. gambiae s.s. from Nigeria. Bioassay, synergist
      and biochemical analysis carried out on resistant and susceptible strains of An.
      gambiae s.s. from the same geographical area revealed >50% of the West African
      kdr mutation in the resistant mosquitoes but <3% in the susceptible mosquitoes.
      Resistant mosquitoes synergized using pyperonyl butoxide before permethrin
      exposure showed a significant increase in mortality compared with the non
      synergized. Biochemical assays showed an increased level of monooxygenase but not
      glutathione-S-transferase or esterase activities in the resistant mosquitoes.
      Microarray analysis using the An. gambiae detox-chip for expression of
      detoxifying genes showed five over-expressed genes in the resistant strain when
      compared with the susceptible one. Two of these, CPLC8 and CPLC#, are cuticular
      genes not implicated in pyrethroid metabolism in An. gambiae s.s, and could
      constitute a novel set of candidate genes that warrant further investigation.

PMID- 18829057
TI  - Isolation and characterization of pathogenic Leishmania turanica from Nesokia
      indica (Rodentia, Muridae) by PCR-RFLP and ITS1 sequencing in Iran.
AB  - Zoonotic cutaneous leishmaniasis, primarily an infection of desert rodents, is an
      important endemic disease in some parts of Iran. In spite of reporting Leishmania
      infection in Nesokia indica microscopically, its role remains unclear in Iran. We
      report the first natural infection by Leishmania turanica in a wild-caught N.
      indica in the west part of Iran, near the border with Iraq. The evidence is in
      the form of PCR-RFLP testing based on internal transcribed spacer 1 (ITS1) rDNA
      with HaeIII enzyme and ITS1 sequence analysis. This isolate was highly pathogenic
      in BALB/c mice and golden hamsters and caused lethal systemic infection in the
      former.

PMID- 18829058
TI  - Risk factors for trachomatous trichiasis in children: cross-sectional household
      surveys in Southern Sudan.
AB  - We have previously documented blinding trachoma to be a serious public health
      problem in Southern Sudan, with an unusually high prevalence of trachomatous
      trichiasis (TT) among children. We aimed to investigate risk factors for TT in
      children in Southern Sudan. Cross-sectional surveys were undertaken in 11
      districts between 2001 and 2006, and eligible participants were examined for
      trachoma signs. Risk factors were assessed through interviews and observations.
      Using logistic regression, associations between TT in children and potential risk
      factors were investigated. In total, 11155 children aged 1-14 years from 3950
      households were included in the analysis. Overall prevalence of TT was 1.5% (95%
      CI 1.1-2.1). Factors independently associated with increased odds of TT in
      children aged 1-14 years were: increasing age (P(trend)<0.001); female gender
      (odds ratio=1.5; 95% CI 1.1-2.1); increasing proportion of children in the
      household with trachomatous inflammation-intense (TI) (P(trend)=0.002); and
      increasing number of adults in the household with TT (P(trend)<0.001). Our study
      revealed risk factors for TT in children consistent with those previously
      reported for TT in adults. While the associations of TT in children with TI in
      siblings and TT in adult relatives merit further investigation, there is an
      urgent need for trachoma prevention interventions and trichiasis surgery services
      that are tailored to cater for young children in Southern Sudan.

PMID- 18829059
TI  - Molecular isolation and characterization of a novel occlusion body protein gene
      from Penaeus monodon nucleopolyhedrovirus.
AB  - The full-length of the occlusion body (OB) protein gene of Penaeus monodon
      nucleopolyhedrovirus (PemoNPV) was successfully isolated. The OB gene sequence
      contained an open reading frame (ORF) of 1359 nucleotides encoding a protein of
      452 amino acid residues with a predicted molecular mass of 50.6 kDa. A putative
      late promoter element, TAAG, was identified 72 nt upstream of the translation
      start site. The amino acid sequences of tryptic digested peptides of PemoNPV OB
      protein obtained from LC-MS analysis matched quite well with various regions of
      deduced amino acid sequences. Recombinant PemoNPV OB proteins specifically
      reacted with monoclonal antibodies to PemoNPV OB protein. After comparison with
      nucleotide database, the PemoNPV OB ORF demonstrated 67% identity to an
      uncharacterized ORF of a baculovirus pathogenic for Penaeus vannamei. However,
      comparison against protein databases revealed no significant homology to other
      known proteins. To our knowledge, this PemoNPV OB gene is the first isolated and
      characterized gene of nucleopolyhedrovirus from shrimp.

PMID- 18829060
TI  - Mouse mammary tumor virus uses mouse but not human transferrin receptor 1 to
      reach a low pH compartment and infect cells.
AB  - Mouse mammary tumor virus (MMTV) is a pH-dependent virus that uses mouse
      transferrin receptor 1 (TfR1) for entry into cells. Previous studies demonstrated
      that MMTV could induce pH 5-dependent fusion-from-with of mouse cells. Here we
      show that the MMTV envelope-mediated cell-cell fusion requires both the entry
      receptor and low pH (pH 5). Although expression of the MMTV envelope and TfR1 was
      sufficient to mediate low pH-dependent syncytia formation, virus infection
      required trafficking to a low pH compartment; infection was independent of
      cathepsin-mediated proteolysis. Human TfR1 did not support virus infection,
      although envelope-mediated syncytia formation occurred with human cells after pH
      5 treatment and this fusion depended on TfR1 expression. However, although the
      MMTV envelope bound human TfR1, virus was only internalized and trafficked to a
      low pH compartment in cells expressing mouse TfR1. Thus, while human TfR1
      supported cell-cell fusion, because it was not internalized when bound to MMTV,
      it did not function as an entry receptor. Our data suggest that MMTV uses TfR1
      for all steps of entry: cell attachment, induction of the conformational changes
      in Env required for membrane fusion and internalization to an appropriate acidic
      compartment.

PMID- 18829061
TI  - Varying efficiency of long-term replication of papillomaviruses in Saccharomyces
      cerevisiae.
AB  - Human papillomaviruses (HPVs) replicate in mitotically active basal
      keratinocytes. Two virally encoded proteins, E1, a helicase, and E2, a
      transcription factor, are important players in replication and maintenance of HPV
      episomes. We previously showed that HPV16 could replicate stably in Saccharomyces
      cerevisiae [Angeletti, P.C., Kim, K., Fernandes, F.J., and Lambert, P.F. (2002)]
      and we identified cis-elements that mediate replication and maintenance [J.
      Virol. 76(7), 3350-3358.; Kim, K., Angeletti, P.C., Hassebroek, E.C., and
      Lambert, P.F. (2005)]. Here, we demonstrate that although multiple HPV genomes
      replicate stably in yeast, they do so with differing long-term efficiency; HPV6
      Ura3 is replicated at the highest copy number, followed by HPV31-Ura3 and HPV16
      Ura3 respectively, HPV11-Ura3 and HPV18-Ura3 were unable replicate without the
      presence of E2 expression and BPV-1-Ura3 was unable to replicate, with or without
      the presence of E2. These studies suggest genotype-specific differences in HPV
      replication and maintenance.

PMID- 18829062
TI  - Coxsackievirus B3 induction of NFAT: requirement for myocarditis susceptibility.
AB  - Ultraviolet (u.v.) inactivated coxsackievirus B3 (CVB3) induces rapid calcium
      flux in naive BALB/c CD4+ T cells. CD4+ cells lacking decay accelerating factor
      (DAF-/-) show little calcium flux indicating that virus cross-linking of this
      virus receptor protein is necessary for calcium signaling in CVB3 infection.
      Interaction of CVB3 with CD4+ cells also activates NFAT DNA binding. To show that
      NFAT activation is crucial to CVB3 induced disease, wild-type mice and transgenic
      mice expressing dominant-negative NFAT (dnNFAT) mutant in T cells were infected
      and evaluated for myocarditis and pancreatitis 7 days later. Inhibition of NFAT
      in T cells prevented myocarditis but had no effect on pancreatitis. Virus titers
      in pancreas were equivalent in wild-type and dnNFAT animals but cardiac virus
      titers were increased in dnNFAT mice. Interferon-gamma (IFN gamma) expression was
      reduced in both CD4+ and V gamma 4+ T cells from dnNFAT mice compared to
      controls. FasL expression by V gamma 4+ cells was also suppressed. Inhibition of
      FasL expression by V gamma 4+ cells is consistent with myocarditis protection in
      dnNFAT mice.

PMID- 18829064
TI  - Integration of toxicological and chemical tools to assess the bioavailability of
      metals and energetic compounds in contaminated soils.
AB  - Bioavailability is critical for understanding effects that might result from
      exposure of biota to contaminated soils. Soils from military range and training
      areas (RTAs) are contaminated principally by energetic materials (EM) and metals.
      Their chemical characteristics are relatively well known and toxicity assessment
      of soils from RTAs are in some cases available. However, bioavailability on these
      sites needs to be comprehensively characterized. A holistic approach to
      bioavailability, incorporating both chemical and earthworm toxicological
      indicators, was applied to soils from an anti-tank firing range at a Canadian
      Forces Base. Results showed that HMX and the metals Zn, Pb, Bi and Cd, though not
      consistently the prevailing toxicants, were the most accessible to earthworms.
      Some metals (notably Cu, Zn, Cr and Bi) were also accumulated in earthworm tissue
      but those were not necessarily expected given their bioaccessibility (i.e., the
      chemical availability of contaminants in the environment for the organisms) at
      the beginning of the exposure. The tested soils impaired earthworm reproduction
      and reduced adult growth. Measurement of selected sublethal parameters indicated
      that lysosomal integrity (determined as the neutral red retention time--NRRT) was
      decreased, while elevated superoxide dismutase (SOD) activity suggested that
      earthworms experienced oxidative stress. The correspondence between the NRRT and
      metal contamination pattern suggested that metals may be the main cause of
      lysosomal disruption in EM-contaminated soils. The approach to bioavailability
      appraisal adopted in this case appears to be a promising practice for site
      specific assessment of contaminated land.

PMID- 18829063
TI  - FOXP3 inhibits HIV-1 infection of CD4 T-cells via inhibition of LTR
      transcriptional activity.
AB  - FOXP3 is a necessary transcription factor for the development and function of
      CD4+ regulatory T-cells (Tregs). The role of Tregs in HIV-1 infection remains
      unclear. Here, we show that expression of FOXP3 in primary human CD4 T-cells
      significantly inhibits HIV-1 infection. Since FOXP3 inhibits NFAT activity, and
      NFAT proteins contribute to HIV-1 transcription, we explore a transcriptional
      repressive function of HIV-1 LTR by FOXP3. Over-expression of FOXP3 in primary
      CD4 T-cells inhibits wild-type HIV-1 LTR reporter activity, and truncation
      mutants demonstrate that repression of the LTR by FOXP3 requires the dual
      proximal NF kappaB/NFAT binding sites. Interestingly, FOXP3 decreases binding of
      NFAT2 to the HIV-1 LTR in vivo. Furthermore, FOXP3 does not inhibit infection of
      HIV-1 NL4-3 which is mutated to disrupt transcription factor binding at either
      proximal NFAT or NF kappaB binding sites. These data suggest that resistance of
      Tregs to HIV-1 infection is due to inhibition of HIV-1 LTR transcription by
      FOXP3.

PMID- 18829065
TI  - Pharmaceutical contamination in residential, industrial, and agricultural waste
      streams: risk to aqueous environments in Taiwan.
AB  - This is a comprehensive study of the occurrence of antibiotics, hormones and
      other pharmaceuticals in water sites that have major potential for downstream
      environmental contamination. These include residential (hospitals, sewage
      treatment plants, and regional discharges), industrial (pharmaceutical production
      facilities), and agricultural (animal husbandries and aquacultures) waste
      streams. We assayed 23 Taiwanese water sites for 97 targeted compounds, of which
      a significant number were detected and quantified. The most frequently detected
      compounds were sulfamethoxazole, caffeine, acetaminophen, and ibuprofen, followed
      closely by cephalexin, ofloxacin, and diclofenac, which were detected in >91% of
      samples and found to have median (maximum) concentrations of 0.2 (5.8), 0.39
      (24.0), 0.02 (100.4), 0.41 (14.5), 0.15 (31.4), 0.14 (13.6) and 0.083 (29.8)
      microg/L, respectively. Lincomycin and acetaminophen had high measured
      concentrations (>100 microg/L), and 35 other pharmaceuticals occurred at the
      microg/L level. These incidence and concentration results correlate well with
      published data for other worldwide locations, as well as with Taiwanese
      medication usage data, suggesting a human contamination source. Many
      pharmaceuticals also occurred at levels exceeding predicted no-effect
      concentrations (PNEC), warranting further investigation of their occurrence and
      fate in receiving waters, as well as the overall risks they pose for local
      ecosystems and human residents. The information provided here will also be useful
      for development of strategies for regulation and remediation.

PMID- 18829066
TI  - Distribution of organochlorine pesticides (OCPs) and polychlorinated biphenyls
      (PCBs) in human serum from urban areas in Korea.
AB  - Concentrations of organochlorine pesticides (OCPs) and polychlorinated biphenyls
      (PCBs) were determined in serum samples from residents of a Korean urban area
      (Seoul). This study was performed on 40 Koreans in the general population, aged
      27-58, who had resided in urban areas for more than 10 years without occupational
      exposure to organochlorine pollutants. To our knowledge, this study was the first
      report on serum concentrations of OCPs in Korean residents. p,p'-DDE, beta-HCH,
      p,p'-DDT, HCB, and trans-nonachlor were the dominant OCPs in most samples. In
      addition, concentrations of 22 OCPs were measured by the isotope dilution method
      with GC-HRMS, which gave accurate and precise data for investigations of trend
      and international comparisons. The dominant PCBs were PCB153, 138, 180, 187, and
      PCB118, which contributed 60% to total PCBs. The median concentrations of total
      OCPs and total PCBs were 315 ng g(-1) lipid and 104 ng g(-1) lipid, respectively.
      In females, the serum concentrations of all determined organochlorine compounds
      except beta-HCH were positively correlated with age, and higher concentrations of
      organochlorine pollutants were found in males than in females. Compared to our
      previous studies, PCB concentrations in serum from urban areas have substantially
      decreased during the last decade leading to the observation that the strict
      regulation of PCBs was helpful in controlling the concentration of PCBs in the
      environment. Extensive monitoring programs are required for evaluating the
      concentrations of OCPs and PCBs in serum samples of the general population as an
      indicator of possible adverse health effects.

PMID- 18829067
TI  - Dissolved metal background levels in marine waters, for the assessment of the
      physico-chemical status, within the European Water Framework Directive.
AB  - The European Water Framework Directive (WFD) has, as its ultimate aim, a
      reduction in the concentrations of hazardous substances in the marine
      environment, i.e. 'background' values. Hence, the determination of natural
      background levels of heavy metals, to distinguish between natural element
      concentrations and anthropogenically-influenced concentrations, is highly
      relevant. Some studies have shown the convenience in the derivation of local
      background levels, especially if they are necessary for environmental assessment.
      Nevertheless, although such studies exist for sediments, there are only a few
      previous investigations on metal background values in sea water. Likewise, there
      is not any standard procedure to determine such levels in waters, nor general
      agreement on the statistical methodologies to be applied. In this contribution,
      background levels of heavy metals (As, Cu, Mn, Ni, Pb and Zn), in estuarine and
      coastal waters within the Basque Country (northern Spain), according to ranges in
      salinity, are estimated using statistical tools. Ni and Pb have been considered
      elsewhere (2455/2001/EC) as priority substances under the WFD. Hence, this
      approach can assist further in the determination of water reference conditions,
      to assess chemical and physico-chemical status in other European countries; this,
      affects, ultimately, the ecological status, as defined within the WFD.

PMID- 18829068
TI  - Heparin-induced thrombocytopenia: diagnosis and management.
AB  - Heparin-induced thrombocytopenia (HIT) is an immune reaction in response to
      platelet factor 4-heparin complexes, which results in increased platelet
      activation and thrombocytopenia beginning on the 4th-5th day after heparin
      exposure induced by IgG antibody production. Platelet activation can lead to
      arterial thrombosis, but more commonly platelet microparticle formation
      contributes to venous thrombosis. Accurate diagnosis of HIT is based on the
      presence of clinical features, including a 50% fall in platelet count,
      appropriate timing of thrombocytopenia, development of new thrombosis despite
      thrombocytopenia and heparin therapy, and the absence of a more likely cause of
      thrombocytopenia. Documentation of an anti-PF4-heparin antibody is necessary, but
      is not sufficient to make the diagnosis since antibody formation occurs in a
      variety of clinical settings without the development of thrombocytopenia or
      thrombosis. Once HIT is suspected or confirmed, all forms of heparin should be
      discontinued and an alternative form of anticoagulation should be administered
      until the platelet count recovers. Treatment options include intravenous
      administration of argatroban, lepirudin, and bivalirudin; subcutaneous
      administration of fondaparinux has also been described. Warfarin therapy, if
      indicated, should be avoided until platelet recovery. Re-exposure to heparin can
      be avoided by use of alternative anticoagulants for most circumstances. Heparin
      induced thrombocytopenia (HIT) has been the focus of increasing attention over
      the past 15-20 years. As interventions for HIT are developed, there is a need to
      accurately diagnose the condition, which can be challenging especially in
      severely ill patients.

PMID- 18829069
TI  - Effects of the contraceptive patch, the vaginal ring and an oral contraceptive on
      APC resistance and SHBG: a cross-over study.
AB  - INTRODUCTION: The transdermal patch (20 microg ethinylestradiol+150 microg
      norelgestromin daily) and the vaginal ring (15 microg ethinylestradiol+120 microg
      etonogestrel daily) are new contraceptives, designed to deliver a low dose of
      hormones, suggesting a low exposure. However, few data are available about their
      risk of venous thrombosis. The objective was to investigate the effect of the
      patch, the ring, and an oral contraceptive (30 microg ethinylestradiol+150 microg
      levonorgestrel daily) on activated protein C sensitivity ratio (APC-sr) and on
      sex hormone-binding globulin (SHBG) levels in plasma. MATERIALS AND METHODS:
      After a two month wash-out, 13 volunteers were randomly assigned to either the
      patch followed by the oral contraceptive or vice versa, or the ring followed by
      the oral contraceptive or vice versa. All treatments lasted two cycles and were
      separated by a wash-out of two cycles. APC-sr and SHBG levels were determined on
      day 18-21 of the second cycle of the wash-out and of each treatment period.
      RESULTS: Compared to the oral contraceptive, both the patch and the ring led to
      higher APC resistance (mean difference APC-sr 1.1; 95% CI 0.67-1.52 and 0.55; 95%
      CI 0.11-1.00, respectively) and higher SHBG levels (mean difference 210 nmol/l;
      95% CI 134-286 and 148 nmol/l; 95% CI 48-248, respectively). CONCLUSION: The
      activity of the protein C system in plasma was impaired more by contraceptive
      patch and vaginal ring than by an oral contraceptive containing the second
      generation progestagen levonorgestrel.

PMID- 18829070
TI  - Known knowns and known unknowns: risks associated with combination antithrombotic
      therapy.
AB  - BACKGROUND: Use of antiplatelet therapy in combination with oral anticoagulants
      remains controversial. The purpose of this article is to review current consensus
      recommendations for antithrombotic therapy, to evaluate risks for bleeding among
      patients taking combination antithrombotic therapy, and lastly to review single
      center data from Kaiser Permanente Colorado detailing clinical outcomes
      associated with combination therapy. METHODS: This was a retrospective,
      longitudinal pharmacoepidemiologic review. Adult patients receiving warfarin
      managed by a clinical pharmacy service who had documented antiplatelet (aspirin,
      clopidogrel, and/or dipyridamole) use (combination therapy cohort) or non-use
      (monotherapy cohort) were identified as of September 30, 2005. Utilizing
      integrated, electronic medical records, anticoagulation-related adverse events
      (death, hemorrhage, thrombosis) and coronary events were identified during a six
      month follow-up (October 2005 through March 2006). Proportions of events were
      compared between cohorts. Independent associations between the cohorts and the
      outcomes were assessed with adjustment for potential confounding factors.
      RESULTS: Data from 2,560 monotherapy and 1,623 combination therapy patients were
      analyzed. Patients in the combination therapy cohort were more likely to have had
      anticoagulation-related hemorrhages (4.2% vs. 2.0%, unadjusted p<0.001). With
      adjustment, combined warfarin and antiplatelet use was independently associated
      with hemorrhagic (OR=2.75; 95% CI 1.44, 5.28) but not coronary (OR=0.99; 95% CI
      0.37, 2.62) events. CONCLUSIONS: At the population level, the hemorrhagic risk
      associated with warfarin therapy combined with antiplatelet therapy appears to
      outweigh the benefits. These findings suggest that clinicians carefully consider
      risks and benefits when prescribing antiplatelet therapy for patients taking
      warfarin who do not meet evidence-based criteria for that approach.

PMID- 18829071
TI  - Preventing and managing bleeding complications in anticoagulated patients: a case
      based approach.
AB  - Bleeding is the most common complication of anticoagulant therapy. Despite the
      frequency of its occurrence, little evidence is available to guide the care of
      anticoagulated patients with, or at high risk of, bleeding. This article
      attempts, using a case based format, to describe common clinical scenarios
      encountered by clinicians who manage anticoagulated patients and who are
      bleeding. The paper is "case based" and narrative since there is little evidence
      to guide practice in this area.

PMID- 18829072
TI  - In vivo age dependency of unfractionated heparin in infants and children.
AB  - INTRODUCTION: Unfractionated Heparin (UFH) is used widely in paediatrics.
      Paediatric specific recommendations for UFH therapy are few, with the majority of
      recommendations being extrapolated from adult practice. In vitro studies have
      shown that this practice may be suboptimal. This study aimed to improve the
      understanding of the impact of age upon UFH response in vivo. MATERIALS AND
      METHODS: This prospective, observational study, conducted in the Paediatric
      Intensive Care Unit (PICU), included: patients 16 years or younger; treated with
      UFH of at least 10 U/Kg/hr. Laboratory analysis included: Antithrombin, APTT,
      Anti-Xa, Anti-IIa and thrombin generation expressed as the Endogenous Thrombin
      Potential. Results were grouped according to patient age (i.e. <1, 1-5, 6-10 and
      11-16 years). RESULTS: 85 patients received an equivalent mean UFH dose with a
      median duration of 3 days. Antithrombin levels were decreased compared to age
      related norms in children up to 11 years of age. APTT results were comparable
      across the age-groups. The Anti-Xa results using two different assays showed a
      trend for lower values in younger children. All children less than one year old
      recorded Anti-Xa values outside the therapeutic range for heparin therapy, for
      both assays. There was a trend for decreased Anti-IIa activity in younger
      children. Endogenous Thrombin Potential showed a significant trend for increased
      inhibition in older children. In vitro Antithrombin supplementation did not
      change the Anti-Xa or thrombin generation. CONCLUSIONS: This study confirms that,
      in vivo, for the same dose of UFH, the anti Xa and anti IIa effect, as well as
      the inhibition of endogenous thrombin potential is age dependent and that these
      differences are not purely AT dependent. The implication is that the
      anticoagulant and antithrombotic effect of a given dose of UFH differs with age.
      Clinical outcome studies to determine the optimal dosing for each age group are
      warranted.

PMID- 18829073
TI  - The predictive value of CD38 positive hepatic stellate cell count for assessing
      disease activity and fibrosis in patients with chronic hepatitis.
AB  - The activation of hepatic stellate cells (HSCs) is a critical event in hepatic
      fibrosis. The objectives of this study were to find out if cluster of
      differentiation 38 (CD38) can be demonstrated immunohistochemically on HSCs in
      liver biopsies from patients with chronic liver disease and if CD38
      immunopositive HSC count is correlated with METAVIR inflammatory and fibrosis
      scores. Immunohistochemical labelling for CD38 was performed on 100 liver
      biopsies from patients with chronic liver disease. The CD38 immunopositive HSCs
      were identified and counted. The CD38 immunopositive HSC count was found to be
      associated with both the METAVIR score and the fibrosis scores. The CD38
      immunopositive HSC count was able to discriminate between no fibrosis and stages
      2, 3 or 4 fibrosis, but could not discriminate between no fibrosis and stage 1
      fibrosis. Using receiver operating characteristic (ROC) curves, a cut-off point
      of 10 HSCs per 10 high power field (hpf), or 25 per 100 hepatocytes, is 80%
      sensitive and 70% specific for predicting fibrosis. The specificity rose to 100%
      in patients with hepatitis C viral (HCV) infection. We conclude that CD38
      positive HSCs can be demonstrated immunohistochemically and that the count is
      highly predictive of moderate to severe hepatic fibrosis.

PMID- 18829074
TI  - The immunohistochemical localization of synaptophysin protein (p38) in the gastro
      entero-pancreatic (GEP) system of reptiles.
AB  - The gastro-entero-pancreatic (GEP) system of four reptilian species: turtle (Emys
      orbicularis), lizards (Lacerta viridis and Lacerta agilis) and snake (Natrix
      natrix) has been investigated immunohistochemically for the presence and
      topographic distribution of synaptophysin. Among the studied reptiles, only in
      turtles were neural, glial and neuroendocrine elements labelled for this marker
      protein. Semi-quantitative evaluation of the immunolabelled neural structures
      distributed throughout the gastroenteric wall revealed, with two exceptions,
      highly significant mean differences between the successive gut segments.
      Significant mean differences were noted also between myenteric and submucosal
      neurons immunolabelled in the various gastroenteric regions. Moreover, the
      comparison of ganglionic perikarya groups showed, at least in the stomach,
      significant mean differences. The amounts of immunopositive glial cells seemed to
      vary similarly to those of nerve fibers along the entire gastrointestinal tract.
      Finally, every "closed" and "open" population of immunopositive epithelial cells
      showed typical fluctuations along the gut. In addition to the distribution of
      synaptophysin in the GEP system of turtles, the above findings furnish evidence
      that this marker protein, which is widespread in mammals, is only occasionally
      expressed in reptiles and probably in most poikilothermic vertebrates.

PMID- 18829075
TI  - Comparison of two periprostatic nerve blockade techniques for transrectal
      ultrasound-guided prostate biopsy: bilateral basal injection and single apical
      injection.
AB  - OBJECTIVES: To investigate the effectiveness of a periprostatic nerve blockade
      technique that relies on a single apical injection of lidocaine. We compared it
      with bilateral injections at the base of the prostate to determine the
      effectiveness of pain control and to compare the technical aspects during
      transrectal ultrasound-guided prostate biopsy. METHODS: The study included
      patients who had elected to undergo transrectal ultrasound-guided prostate needle
      biopsy. The patients were divided into 2 groups according to the anesthesia
      technique they would receive. In the bilateral basal injection group (n = 60), 2
      injections of 5 mL lidocaine were administered just lateral to the junction
      between the base of the prostate and the seminal vesicles on both sides. In the
      single apical injection group (n = 57) 5 mL of lidocaine was injected at the apex
      of the prostate to provide the distribution of lidocaine toward the base of the
      prostate under Denonvilliers fascia. RESULTS: Both techniques were effective
      regarding pain control, with better results in the single apical injection group.
      The mean numeric rating scale score was 2.46 +/- 1.03 and 2.01 +/- 1.02 in the
      bilateral basal injection and single apical injection groups, respectively (P =
      .01). CONCLUSIONS: The results of this randomized prospective study suggest that
      both the single apical injection and the bilateral basal injection techniques are
      effective in terms of pain prevention during transrectal-ultrasound-guided
      prostate biopsy. The main advantage of the single apical injection technique is
      its ease of use and the requirement for one half the amount of local anesthetic
      agent.

PMID- 18829076
TI  - Robotic-assisted endoscopic inguinal lymphadenectomy.
AB  - INTRODUCTION: Open inguinal lymphadenectomy is a well-established therapeutic and
      diagnostic option for patients with invasive penile squamous cell carcinoma who
      are at risk of regional and distant metastases. We report the use of endoscopic
      robotic-assisted bilateral inguinal lymph node dissections in a patient with
      palpable inguinal nodes despite oral antibiotics. TECHNIQUE: A 2-cm mid-thigh
      incision was made to develop a plane just deep to Camper's (fatty) fascia. Once a
      sufficient working space was created to place 3 robotic ports and 1 assistant
      port, subcutaneous gas was instilled, and the robotic device was docked and used
      to perform the dissection. The surgical approach replicated the principles of
      open techniques such that the contents of the femoral canal were dissected to the
      inguinal ligament superiorly, the sartorius muscle laterally, and the adductor
      longus muscle medially to include both superficial and deep lymph nodes in the
      dissection template. CONCLUSIONS: To our knowledge, this is the first report of
      an endoscopic robotic-assisted inguinal lymph node dissection. A minimally
      invasive approach circumventing the need for thick skin flaps, the improved
      flexibility afforded by robotic instruments, and the improved magnification could
      decrease the morbidity associated with inguinal lymphadenectomy while maintaining
      oncologic principles.

PMID- 18829077
TI  - Prevalence and associated factors of overactive bladder in Korean children 5-13
      years old: a nationwide multicenter study.
AB  - OBJECTIVES: To estimate the prevalence of overactive bladder (OAB) in Korean
      children, 5-13 years of age, and to assess the associated factors for OAB.
      METHODS: A randomly selected cross-section study was conducted in 26
      kindergartens and 27 elementary schools nationwide in Korea. A total of 19 240
      children were included; a parent was asked to complete the questionnaires, which
      included items about OAB and voiding and defecating habits. OAB was defined as
      urgency with or without urge incontinence, usually with increased daytime
      frequency and nocturia (International Children's Continence Society, 2006). Its
      prevalence and associated factors were also investigated. RESULTS: The response
      rate for the questionnaires was 85.84%. The overall prevalence of OAB was 16.59%.
      The prevalence of OAB decreased with age from 22.99% to 12.16% (P = .0001). The
      overall incidence of wet and dry OAB was 26.97% and 73.03%, respectively.
      Compared with normal children, those with OAB had a greater prevalence of
      nocturnal enuresis, constipation, fecal incontinence, urinary tract infection,
      delayed bladder control, and poor toilet facilities (P < .05). The incidence of
      increased daytime frequency and urge incontinence was 3.69% and 2.31% (P = .009)
      and 26.97% and 14.78% (P = .0001) in OAB and non-OAB children, respectively. The
      corresponding prevalence decreased with age from 5.04% to 3.06% and from 45.74%
      to 18.50% in OAB children (P = .0001). CONCLUSIONS: The overall prevalence of OAB
      in Korean children, 5-13 years of age, was 16.59% and decreased with age.
      Nocturnal enuresis, constipation, fecal incontinence, history of urinary tract
      infection, delayed bladder control, and poor toilet facilities might be factors
      associated with the development of OAB.

PMID- 18829078
TI  - Eight years' experience with high-intensity focused ultrasonography for treatment
      of localized prostate cancer.
AB  - OBJECTIVES: To report on the long-term results of high-intensity focused
      ultrasonography (HIFU) in the treatment of localized prostate cancer. METHODS:
      Patients with clinical Stage T1-T2N0M0, biopsy-proven, localized prostate cancer,
      with a serum prostate-specific antigen (PSA) level of <or=20 ng/mL, Gleason score
      of <or=7, and with no previous curative prostate cancer treatment, were included.
      All patients underwent HIFU using the Ablatherm device and were required to have
      a minimal follow-up of 3 years after the last HIFU session to be included in this
      analysis. Follow-up included PSA measurement and biopsy performed 3-6 months
      after treatment and in conjunction with an increasing PSA level. Biochemical
      failure was defined according to the Phoenix definition (PSA nadir + 2 ng/mL). In
      determining the disease-free survival rate, treatment was considered to have
      failed if any of the following occurred: biochemical failure, positive biopsy
      findings, or the initiation of salvage treatment. RESULTS: The study included 163
      patients. Within the 4.8 +/- 1.2 years of follow-up, no patient died of prostate
      cancer. Of the 163 patients, 86.4% achieved a PSA nadir of <1 ng/mL and 92.7% had
      negative post-treatment biopsy findings. The actuarial biochemical survival rate
      at 5 years was 75%. The actuarial disease-free survival rate at 5 years was 66%,
      with salvage treatment initiated for 12% of the patients. On multivariate
      analysis, the pretreatment PSA level was the only statistically significant
      predictive factor of recurrence (P = .005). CONCLUSIONS: The results after long
      term follow-up have indicated that HIFU is an efficient and safe treatment for
      patients with localized prostate cancer.

PMID- 18829079
TI  - A new technique for laparoscopic vesicourethral anastomosis: preliminary report.
AB  - OBJECTIVES: To introduce a new and easy technique to perform laparoscopic
      vesicourethral anastomosis with a single-suture, single-knot, running procedure.
      METHODS: We have performed 350 laparoscopic radical prostatectomies. In a
      prospective study, we evaluated a new anastomosis technique in 50 consecutive
      cases. A multiple knot is prepared at 4 cm from the end of a suture. Then the
      running suture is started at the bladder neck at 4 o'clock. The posterior plate
      is maintained open for the first throws, and the suture is pulled only after the
      third passage at the bladder neck. Then the running suture is completed clockwise
      and finally tied to the 4-cm tail. RESULTS: Use of this technique in 50 patients
      was compared with use of a double running suture in 50 other patients. The 2
      groups were comparable. The new procedure was related to a decreased anastomotic
      time, without complications, with no leak at catheter removal at postoperative
      day 5 or 6. CONCLUSIONS: The experience with this original anastomosis is still
      preliminary, but the results are very promising, and we would like to propose it
      to laparoscopic urologists.

PMID- 18829080
TI  - Is injection therapy for stress urinary incontinence dead? No.

PMID- 18829081
TI  - Inverse association between histologic inflammation in needle biopsy specimens
      and prostate cancer in men with serum PSA of 10-50 ng/mL.
AB  - OBJECTIVES: To investigate the effect of the presence of histologic inflammation
      in needle biopsy specimens on the detection of prostate cancer (PCa) in men with
      a high serum prostate-specific antigen (PSA) level. METHODS: This study included
      143 consecutive patients with serum a PSA level of 10-50 ng/mL who had undergone
      initial needle biopsies of the prostate. We defined moderate or severe
      inflammation in the biopsy specimens, according to De Marzo et al., as the
      presence of histologic inflammation. RESULTS: Of the 143 patients, 86 and 57 were
      diagnosed with PCa (PCa group) or benign prostatic disease (BPD group),
      respectively. The prostate volume and transition zone volume in the PCa group
      were significantly smaller than those in the BPD group, and the serum PSA level,
      PSA density (PSAD), and PSAD in the transition zone were significantly greater
      than those in the BPD group. A significant difference was found in the incidence
      of histologic inflammation between the PCa (40.7%) and BPD (73.7%) groups. Among
      the factors examined, the PSAD and the presence of histologic inflammation
      appeared to be independently associated with the detection of PCa. Furthermore,
      the combined consideration of these 2 independent factors could differentiate PCa
      from BPD in the biopsy specimens with a sensitivity, specificity, positive
      predictive value, and negative predictive value of 87.2%, 63.2%, 78.1%, and
      76.6%, respectively. CONCLUSIONS: It seems possible to avoid unnecessary repeat
      biopsy using the PSAD and the presence of histologic inflammation in biopsy
      specimens in patients with continuously elevated serum PSA levels after the
      initial biopsy.

PMID- 18829083
TI  - Collagen remodeling and suburethral inflammation might account for preserved anti
      incontinence effects of cut polypropylene sling in rat model.
AB  - OBJECTIVES: To determine whether the inflammatory responses or collagen
      remodeling in suburethral tissue could have contributed to the preserved anti
      incontinence effects of a cut polypropylene sling. METHODS: Stress urinary
      incontinence was created in 60 age-matched female Sprague-Dawley rats that were
      subsequently randomized into 3 equal-size groups according to surgical procedure:
      placement of a vaginal suburethral sling, placement of a vaginal suburethral
      sling in which the suburethral portion of the sling was immediately cut, and sham
      surgery without placement of the sling. In a previous study, the leak point
      pressure measurements were obtained on these rats 6 weeks after surgery. The rats
      were then killed, the urethrovaginal tissue was harvested (cross-section of the
      entire urethra and anterior vagina) from 30 animals (10 from each experimental
      group), and the tissue was stained with hematoxylin-eosin and Masson's trichrome
      for histopathologic studies and picrosirius red for collagen fibers. RESULTS: As
      previously published, the median leak point pressures were similarly and
      significantly increased in the rats in the intact and cut sling groups compared
      with those in the sham surgery group. The inflammatory mediators and interstitial
      edema were similarly increased in the intact and cut sling specimens compared
      with the sham surgery specimens. Under polarized light, picrosirius red-stained
      specimens from the sham surgery animals appeared to be composed of collagen that
      predominately birefringed red to yellow (typical of type I collagen). The
      picrosirius red-stained cut and intact sling specimens appeared to contain
      collagen fibers that predominately birefringed green (typical of type III
      collagen). CONCLUSIONS: Histologic changes, including inflammation, localized
      edema, and differential collagen remodeling, might contribute to the preserved
      anti-incontinence mechanisms of cut or intact polypropylene slings observed
      clinically.

PMID- 18829084
TI  - Bilateral renal infarction.
AB  - A 34-year-old man was admitted for acute onset of left lower abdominal pain
      associated with fever. His medical history was unremarkable, and the physical
      examination revealed bilateral flank tenderness. Bilateral renal infarction was
      diagnosed and demonstrated by computed tomography.

PMID- 18829085
TI  - Neoadjuvant cisplatin and etoposide followed by radical hysterectomy for stage 1B
      2B cervical cancer.
AB  - OBJECTIVES: We aimed to determine the efficacy and feasibility of neoadjuvant
      chemotherapy (NACT) using cisplatin and etoposide in patients with locally
      advanced cervical cancer. METHODS: Previously untreated patients with
      histologically confirmed stage 1B-2B cervical cancer were treated with three
      courses of NACT (60 mg/m2 cisplatin on days 1 and 2 plus 100 mg/m2 etoposide on
      day 1) every 10 days. NACT was followed within 2-3 weeks by radical hysterectomy
      with lymph node dissection. RESULTS: From 1999 to 2004, 112 patients were
      enrolled and 99 patients were evaluable. All eligible patients had radical
      surgery after NACT. Hematologic toxicity was the most common side effect, and the
      level of toxicity was acceptable. The overall pathologic response rate was 69.7%
      (69/99). The median follow-up period was 49 months, and the 5-year overall and
      progression-free survival rates were 88.1% and 60.5%, respectively. CONCLUSION:
      NACT with cisplatin and etoposide for patients with locally advanced cervical
      cancer is promising and has an acceptable toxicity profile. The regimen timing
      (every 10 days) did not delay the optimal time for radical treatment.

PMID- 18829086
TI  - Do racial/ethnic disparities exist in the utilization of high-volume surgeons for
      women with ovarian cancer?
AB  - OBJECTIVE: Determine if racial/ethnic disparities exist for access to high-volume
      surgeons (HVS) for patients with ovarian cancer. METHODS: Retrospective study of
      ovarian cancer surgeries identified by the California Cancer Registry (CCR)
      linked to hospital discharge data (1991-2002). Surgeon volume was defined as HVS
      (>10 ovarian cancer surgeries/year), middle volume (MVS; 2-9/year), and low
      volume (LVS; </=1/year). Multivariate ordered logistic regression predicting
      surgeon volume provided estimates of relative risk (RR) of surgeon volume by
      patient race/ethnicity. RESULTS: 13,186 women had ovarian cancer (mean age 57.8
      years; 72% non-Hispanic White (NHW), 4% Black, 8% Hispanic). 25% of cases were
      treated by HVS, 31% by MVS, and 44% by LVS. Compared to NHW, Black (RR: 0.70,
      p<0.05) and Hispanic women (RR: 0.75, p<0.05) were less likely to have care by a
      HVS. Hispanic women were significant more likely to have surgery by LVS (RR: 1.1;
      p<0.05). CONCLUSIONS: Disparities in access to HVS for cancer care exist for
      minority women. Selective referral to high-volume providers should be considered
      to improve outcomes among minority women.

PMID- 18829087
TI  - A phase II trial of paclitaxel poliglumex in recurrent or persistent ovarian or
      primary peritoneal cancer (EOC): a Gynecologic Oncology Group Study.
AB  - OBJECTIVES: To estimate the anti-tumor activity and toxicity of paclitaxel
      poliglumex (PPX) in patients with persistent or recurrent ovarian, fallopian tube
      or primary peritoneal cancer (EOC) in second or third line treatment. METHOD:
      Twenty-five patients received PPX at 235 mg/m(2) every 21 days (Cohort 1). At a
      planned analysis following first stage accrual, the dose was reduced to 175
      mg/m(2) Cohort 2) for additional accrual to 78 patients. RECIST and CTC toxicity
      criteria were used. RESULTS: Patients received PPX in the second line (15%) and
      third line (85%) setting. In cohort 2, 25 out of 47 determined cases (53%) were
      platinum resistant and 17 out of 43 determined cases (40%) were taxane-resistant.
      The overall response rates for cohort 2 were 0/49 (0%) CR, 8/49 (16%) PR, and
      20/49 (41%) SD. The median progression-free survival (PFS) was 2.8 months (95% CI
      1.48-4.8 months) and median overall survival (OS) was 15.4 months. The most
      frequent grade III or IV toxicities in cohort 2 were: neutropenia (24%/20%),
      constitutional (8%/0%), gastrointestinal (6%/0%), and neuropathy (24%/0%).
      CONCLUSION: PPX at 175 mg/m(2) every 21 days has a modest activity of limited
      duration when given as second or third line therapy in patients with epithelial
      ovarian or primary peritoneal cancer. The incidence of neuropathy using this dose
      in recurrent ovarian cancer is higher than predicted from studies in other tumors
      with PPX. The Gynecology Oncology Group (GOG) is currently exploring its use at
      135 mg/m(2) every 28 days in a randomized trial evaluating maintenance
      chemotherapy in first remission.

PMID- 18829088
TI  - Combination gemcitabine, platinum, and bevacizumab for the treatment of recurrent
      ovarian cancer.
AB  - OBJECTIVE: To describe the response rate (RR), progression-free survival (PFS),
      and toxicity profile of combination gemcitabine, platinum, and bevacizumab (GPB)
      for the treatment of recurrent epithelial ovarian cancer (EOC). METHODS: A chart
      review of all patients with recurrent EOC who were treated with D1, D15 GPB in a
      28-day cycle at a single institution was performed. Standard doses were
      gemcitabine 1000 mg/m(2), cisplatin 30 mg/m(2) or carboplatin AUC 3, and
      bevacizumab 10 mg/kg. All patients were analyzed for toxicity. RR and PFS were
      assessed in all patients who received at least 2 cycles of GPB. RESULTS: Thirty
      five patients were identified, and 33 received at least 2 cycles of GPB. The
      majority of patients (80%) were platinum sensitive. Patients received a median of
      6 cycles of GPB (range 1-24). Sixteen patients (48%) had a complete response
      (CR), and 10 patients (30%) had a partial response (PR), for a total RR of 78%.
      An additional 5 patients (15%) had stable disease, and only 2 (6%) patients had
      progressive disease. The median overall PFS was 12 months (95% CI 7-15), with a
      median follow-up time of 10 months (2-22). Two patients (6%) had bowel
      perforations, and both survived. Hematologic toxicities were most common, with
      29% and 14% of patients experiencing grade 3 or 4 neutropenia and
      thrombocytopenia respectively. CONCLUSIONS: The combination of GPB demonstrated
      excellent efficacy for the treatment of recurrent EOC. However, serious
      toxicities occurred, and the safety profile of this combination requires further
      study.

PMID- 18829089
TI  - hLH/hCG-receptor expression correlates with in vitro invasiveness in human
      primary endometrial cancer.
AB  - OBJECTIVE: Endometrial cancer (EC) is the most frequent cancer of the female
      genital tract. It has been hypothesized that those ECs that occur in the
      postmenopausal period, might be sensitive to elevated levels of luteinizing
      hormone/human chorionic gonadotropin (LH/hCG). Based on previous indications, we
      analyzed the functional expression of LH/hCG receptors (LH/hCG-R) in primary ECs.
      METHODS: We studied a cohort of primary ECs, in which both the LH/hCG-R mRNA and
      the LH/hCG-R protein were analyzed. Results were correlated with both clinical
      pathological data and the effects of LH addition on cell invasion in vitro.
      RESULTS: The LH/hCG-R mRNA levels ranged from 4.67 e(-02) to 2.36 e(+03). The
      transcript was properly translated into a functional LH/hCG-R protein. The
      analysis of cell invasion in vitro in response to LH/hCG allowed us to divide the
      EC samples into two groups, one with a null or very low response (non
      responders=NR) and the other with a significant response to LH (responders=R).
      The two groups had significantly different levels of LH/hCG-R mRNA expression:
      the NR group had a median value of 1.40 e(+)(00), while the R group of 7.42
      e(+)(01) (p=0.043). CONCLUSION: In primary ECs a statistically significant
      correlation emerged between the levels of LH/hCG-R mRNA and the LH-induced cell
      invasion in vitro. These results suggest that therapies aimed at decreasing LH
      levels, through Gonadotropin Releasing Hormone (Gn-RH) analogues, could produce
      benefits in the treatment of recurrent or metastatic EC, especially in patients
      displaying high LH/hCG-R levels.

PMID- 18829090
TI  - Biologic therapeutics and molecular profiling to optimize wound healing.
AB  - Non-healing wounds represent a significant cause of morbidity and mortality for a
      large portion of the adult population. Wounds that fail to heal are entrapped in
      a self-sustaining cycle of chronic inflammation leading to the destruction of the
      extracellular matrix. Among cancer patients, malnutrition, radiation, physical
      dehabilitation, chemotherapy, and the malignancy itself increase the likelihood
      of chronic wound formation, and these co-morbidity factors inhibit the normal
      wound healing process. Current wound treatments are aimed at some, but not all,
      of the underlying causes responsible for delayed healing of wounds. These
      impediments block the normal processes that allow normal progression through the
      specific stages of wound healing. This review summarizes the current information
      regarding the management and treatment of complex wounds that fail to heal
      normally and offers some insights into novel future therapies [Menke N, Ward KR,
      Diegelmann R. Non-healing wounds. Emerg Med Rep 2007; 28(4).,Menke NB, Ward KR,
      Witten TM, Bonchev DG, Diegelmann RF. Impaired wound healing. Clin Dermatol
      2007;25:19-25].

PMID- 18829091
TI  - Comparison of outcomes and cost for endometrial cancer staging via traditional
      laparotomy, standard laparoscopy and robotic techniques.
AB  - OBJECTIVES: The study purpose was to compare hysterectomy and lymphadenectomy
      completed via robotic assistance, laparotomy, and laparoscopy for endometrial
      cancer staging with respect to operative and peri-operative outcomes,
      complications, adequacy of staging, and cost. METHODS: One hundred and ten
      patients underwent hysterectomy with bilateral salpingo-oophorectomy, pelvic and
      para-aortic lymphadenectomy for endometrial cancer staging. All cases were
      performed by a single surgeon, at a single institution (40 robotic, 40
      laparotomy, and 30 laparoscopic) and were retrospectively reviewed to compare
      demographics and peri-operative variables including, operative time, estimated
      blood loss, lymph node count, hospital stay, complications, and return to normal
      activity. Additionally, a cost comparison between all three modalities was
      performed. RESULTS: Patients undergoing robotic assisted hysterectomy and staging
      experienced longer operative time than the laparotomy cohort with no difference
      in comparison to the laparoscopic cohort (184 min, 108.6 min, 171 min, p<0.0001,
      p=0.14). Estimated blood loss was significantly reduced for the robotic cohort in
      comparison to the laparotomy cohort and comparable to laparoscopic cohort (166
      cc, 316 cc, 253 cc, p=0.01, p=0.25). The complication rate was lowest in the
      robotic cohort (7.5%) relative to the laparotomy (27.5%) and laparoscopic cohorts
      (20%) (p=0.015, p=0.03). Average return to normal activity for the robotic
      patients was significantly shorter than those undergoing laparotomy (24.1 days
      versus 52 days, p<0.0001) and those undergoing laparoscopy (31.6 days, p=0.005).
      Lymph node retrieval did not differ between the 3 groups (robotic 17 nodes,
      laparotomy 14 nodes, laparoscopic 17 nodes). The total average cost for
      hysterectomy with staging completed via laparotomy was $12,943.60, for standard
      laparoscopy $7569.80, and for robotic assistance $8212.00. The difference in cost
      between laparotomy and robotic cohorts was significant p=0.0001 while there was
      no statistically significant difference in cost between laparoscopy and robotic
      cohorts p=0.06. CONCLUSIONS: Robotic hysterectomy provides comparable node
      retrieval to laparotomy and laparoscopic procedures in the case of the
      experienced laparoscopic surgeon. While robotic hysterectomy takes longer to
      perform than hysterectomy completed via laparotomy, it is equivalent to
      laparoscopic hysterectomy and provides the patient with a more expeditious return
      to normal activity with reduced post-operative morbidity. Additionally, the
      average cost for hysterectomy and staging was highest for laparotomy, followed by
      robotic, and least for standard laparoscopy.

PMID- 18829092
TI  - Abdominal radical trachelectomy for invasive cervical cancer: a case series and
      literature review.
AB  - OBJECTIVE: The objective of this study was to review our experience with
      abdominal radical trachelectomy in patients with early-stage cervical cancer.
      METHODS: We performed a retrospective review of all patients who underwent an
      abdominal radical trachelectomy at the Instituto de Cancerologia--Clinica las
      Americas in Medellin, Colombia, between April 2002 and January 2008. Data
      collected included age, stage, histopathologic subtype, tumor size, evidence of
      lymph-vascular space invasion, estimated blood loss, number of perioperative
      blood transfusions, number and disease status of lymph nodes removed, disease
      status of surgical specimen, length of hospital stay, intraoperative and
      postoperative complications, follow-up time, and fertility outcomes. RESULTS:
      Fifteen patients underwent an abdominal radical trachelectomy during the study
      period. The median patient age was 30 years (range, 25-38). Three patients had
      stage IA2 and 12 had stage IB1 cervical cancer. Eleven patients had squamous cell
      carcinoma and 4 had adenocarcinoma. Thirteen patients were diagnosed by cervical
      conization and 2 by colposcopically directed biopsy. All patients had tumors
      smaller than 2 cm. The median estimated blood loss was 400 ml (range, 200-1000).
      The median surgical time was 265 min (range, 210-330). The median number of units
      of packed red blood cells transfused per patient was 2. The median number of
      lymph nodes removed was 26 (range, 11-48). The median length of hospitalization
      was 3 days (range, 2-7). The median follow-up time was 32 months (range, 5-32).
      There was 1 intraoperative complication and 6 postoperative complications in 4
      patients. No patient has had a recurrence. Three patients were able to conceive
      spontaneously; 1 delivered at 31 weeks' gestation, and 2 delivered at term.
      CONCLUSION: Abdominal radical trachelectomy is feasible and can be performed
      safely in a developing country in well-selected patients with early cervical
      cancer who wish to preserve their fertility.

PMID- 18829093
TI  - Seminal plasma damages sperm during cryopreservation, but its presence during
      thawing improves semen quality and conception rates in boars with poor post-thaw
      semen quality.
AB  - To determine the effects of seminal plasma during and after cyopreservation on
      post-thaw sperm functions in semen from poor freezability boars, seminal plasma
      was removed immediately after collection, and sperm was subjected to cooling and
      freezing. Removal of seminal plasma did not significantly affect post-thaw sperm
      motility in good freezability boars; however, in boars with poor freezability, it
      increased post-thaw motility relative to control sperm cooled with seminal plasma
      (64.5+/-3.4% vs. 30.9+/-3.1%, P<0.01). Freezing sperm without seminal plasma
      increased both loss of the acrosome cap (37.5+/-1.6% vs. 18.4+/-2.8%, P<0.01) and
      expression of a 15 kDa tyrosine-phosphorylated protein (capacitation marker) in
      thawed sperm relative to controls; the addition of 10% (v/v) seminal plasma to
      the thawing solution significantly suppressed both changes and increased
      conception rate to AI (70% vs. 9% in the control group, P<0.05). In conclusion,
      our novel cryopreservation and thawing method increased the success of AI with
      frozen-thawed porcine semen, particularly from boars with poor post-thaw semen
      quality.

PMID- 18829094
TI  - Induction of abortion with aglepristone significantly changed the expression of
      progesterone and estrogen receptors in canine endometrial stromal cells.
AB  - In the present study, resorption/abortion was induced between days 25 and 45 of
      gestation with aglepristone (group IRA, n=10). The aim was to observe the change
      in the distribution of progesterone (PR) and estrogen receptors (ER), in
      comparison to a group of spontaneous resorptions/abortions (group SRA, n=5), and
      a further group of normal healthy pregnant animals, ovariohysterectomized between
      days 25 and 45 of gestation (controls, n=7). The receptors were assessed by means
      of immunohistochemistry (IHC) and RT-PCR, at the placental and interplacental
      sites of the uterine horn as well as in the corpus uteri. Significant differences
      were observed between the controls on one side and the groups of
      resorption/abortion on the other side. The total scores of the progesterone
      receptors (TPR) in the placental and interplacental part of the uterine horn, was
      significantly lower in the endometrial stromal cells (ESC) of the control group
      than in those of the SRA- and IRA-group, respectively (placenta: 5.8 vs. 6.5 and
      6.7, p<0.01; interplacental sites: 5.6 vs. 6.6 and 6.6, p<0.05). In contrary, the
      total scores of the estrogen receptors (TER) at interplacental sites and the
      corpus uteri, respectively, was significantly higher in the myometrial smooth
      muscle cells (MSMC) and the ESC (p<0.05) of the controls. We therefore conclude,
      that the here observed differences between groups point to an up-regulation of
      TPR- and a down-regulation of TER-scores in endometrial stromal cells at
      different uterine sites during resorption/abortion, which indicates a special
      role of these cells.

PMID- 18829095
TI  - Word and letter string processing networks in schizophrenia: evidence for
      anomalies and compensation.
AB  - Imaging studies show that in normal language correlated activity between anterior
      and posterior brain regions increases as the linguistic and semantic content
      (i.e., from false fonts, letter strings, pseudo words, to words) of stimuli
      increase. In schizophrenia however, disrupted functional connectivity between
      frontal and posterior brain regions has been frequently reported and these
      disruptions may change the nature of language organization. We characterized
      basic linguistic operations in word and letter string processing in a region-of
      interest network using structural equation modeling (SEM). Healthy volunteers and
      volunteers with schizophrenia performed an fMRI one-back matching task with real
      words and consonant letter strings. We hypothesized that left hemisphere network
      dysfunction in schizophrenia would be present during processes dealing with
      linguistic/semantic content. The modeling results suggest aberrant left
      hemisphere function in schizophrenia, even in tasks requiring minimal access to
      language. Alternative mechanisms included increases in right hemisphere
      involvement and increased top-down influence from frontal to posterior regions.

PMID- 18829096
TI  - PMMA-grafted nanoclay as novel filler for dental adhesives.
AB  - OBJECTIVE: The aim of this study was to investigate the benefits of incorporation
      of poly(methyl methacrylate)-grafted-nanoclay on the bond strength of an
      experimental one-bottle dentin bonding system. The effect of the modification on
      the stability of the nanoparticle dispersion in the dilute adhesive was also
      studied. MATERIALS AND METHODS: Poly(methyl methacrylate) was grafted onto the
      pristine Na-MMT nanoclay (Cloisite Na(+)) through the free radical polymerization
      of methyl methacrylate in an aqueous media in the presence of ammonium persulfate
      as initiator. A reactive surfactant (AMPS) was also used in the reaction recipe
      to provide active sites on the surface of the nanoclay. The grafting
      polymerization reaction was carried out at 70 degrees C. The PMMA-g-nanoclay was
      then coagulated in methanol and filtered. The resulting PMMA-g-nanoclay was
      characterized using FTIR, TGA, X-ray diffraction (XRD) and particle size
      distribution analysis. The modified nanoclay was added to an experimental dentin
      bonding system as filler and the morphology of the nanoclay layers in the
      adhesive matrix was studied using TEM and XRD. Shear bond strength of the
      adhesives containing different filler contents was tested on the caries-free
      extracted human premolar teeth. The mode of failure was studied by scanning
      electron microscopy. The stability of the nanoclay dispersion in the dilute
      adhesive was also studied using a separation analyzer. The results were then
      statistically analyzed and compared. RESULTS: The grafting of
      poly(methylmethacrylate) onto the nanoclay was confirmed and the results revealed
      a partially exfoliated structure for the PMMA-g-nanoclay. Incorporation of the
      modified nanoclay provided a dentin bonding system with higher shear bond
      strength. The dispersion stability of the modified nanoparticles in the dilute
      adhesive was also increased more than 40 times in comparison with the pristine
      nanoclay. SIGNIFICANCE: The grafting modification provided nanoclay particles
      with higher dispersion stability than pristine Na-MMT nanoclay in a dilute dentin
      bonding system. Incorporation of the modified nanoclay into the bonding system
      provided higher shear bond strength. The finding would be beneficial in producing
      nano-filler containing adhesive systems.

PMID- 18829097
TI  - Approach for valuating the influence of laboratory simulation.
AB  - OBJECTIVE: The aim of this investigation was to determine the fracture resistance
      of zirconia fixed partial dentures (FPDs) after laboratory simulation. Failure
      type and failure rates during simulation were compared to available clinical data
      for estimating the relevance of the simulation. METHODS: 32 FPDs were fabricated
      of a zirconia ceramic and a corresponding ceramic veneer. The FPDs were
      adhesively bonded on human molars and artificial aging was performed for
      investigating the survival rate during thermal cycling and mechanical loading
      (TCML1; 3.6Mio x 50N ML). Survival rates were compared to available clinical data
      and the TCML parameter "mastication force" was adapted accordingly for a second
      TCML run (TCML2; 3.6Mio x 100N ML). The fracture resistance of the FPDs which
      survived TCML was determined. FPDs were examined without TCML (control) or after
      TCML according to literature (1.2Mio x 50N ML). Data were statistically analyzed
      (Mann-Whitney U-test) and curve fitting/regression analysis of the survival rates
      was performed. RESULTS: TCML reduced survival rates down to 63%. Failures during
      TCML were chipping off of the veneering ceramic, no zirconia framework was
      damaged. Under clinical conditions comparable failures (chipping) are reported.
      The clinical survival rate (approximately 10%) is lower compared to TCML data
      because of the short period of observation. The fracture resistance after TCML
      was significantly reduced from 1058N (control) to values between 320 and 533N.
      CONCLUSION: The results indicate that TCML with 1.2Mio x 50N provides a
      sufficient explanatory power. TCML with prolonged simulation time may allow the
      definition of a mathematical model for estimating future survival rates.

PMID- 18829098
TI  - Exudates of different marine algae promote growth and mediate trace metal binding
      in Phaeodactylum tricornutum.
AB  - Phaeodactylum tricornutum was grown in filtered natural seawater enriched with
      nitrate, phosphate, and silicate only (control) or with exudates from itself,
      from Emiliania huxleyi (a coccolithophore micro-alga), Porphyra spp. (a red macro
      alga) or Enteromorpha spp. (a green macro-alga). Cathodic (and anodic) stripping
      voltammetry (C(A)SV) were used to determine the concentrations of trace metals,
      both in the medium and in the algae, as well as total Cu-complexing organic
      ligands in the medium and, among these, some thiols (compounds identified as
      cysteine- or as glutathione by CSV). Exudates of different marine micro- and
      macro-algae could cause allelopathic effects in P. tricornutum cultures. Cell
      yield of P. tricornutum was increasingly promoted by exudates of E. huxleyi
      >Porphyra >Enteromorpha. Although exudates strongly complex Cu (and probably
      other metals), their presence promoted Cu uptake. Significant changes of Ni, Cd,
      Fe, Zn and Mn uptake by P. tricornutum were also observed in the presence of
      exudates of different algal species. In addition, both intensity of production
      and nature of exudates released by P. tricornutum were markedly influenced by the
      presence of exudates of other algae, the allelopathic effects being very specific
      (variable from one species to another). Allelopathy will probably also occur in
      the aquatic environment, although to a lesser extent than in cultures,
      particularly during bloom events and may have effects on both chemical speciation
      and bioavailability of chemicals to phytoplanktonic species. Such changes might
      cause the predominance of some species over other species. Therefore, in future
      in vitro culture studies with the purpose of using them as models of the real
      environment, more attention should be paid to the role of algal exudates, in
      order to improve the environmental relevance and significance of the results.

PMID- 18829099
TI  - Habitat continuity effects on gradients of fish biomass across marine protected
      area boundaries.
AB  - Marine protected areas (MPAs) could be useful as fisheries management tools for
      the exportation of pelagic eggs, larvae and adult fish. A decreasing gradient of
      fish biomass across MPAs boundary may indicate export. We determine whether
      gradients of decreasing biomass of fish assemblage occurred in Tabarca Marine
      Reserve over two habitats with different continuity across the boundaries, to
      test if the patchy nature of the marine environment might act as a barrier for
      the fish export. In general, significant decreasing gradients in total fish
      biomass and biomass of some species were observed on P. oceanica and rocky
      substrates, independently of their different continuity through the reserve
      boundaries. Changes in the multivariate structure of the fish assemblage were
      correlated with the distance from integral reserve. All of these results support
      the hypothesis that the exportation of adult fish from Tabarca Marine Reserve
      occurs, and this process may influence the surrounding fished areas.

PMID- 18829100
TI  - Accelerated wound healing by smad3 antisense oligonucleotides-impregnated
      chitosan/alginate polyelectrolyte complex.
AB  - Smad3 mediates the intracellular signaling of TGF-beta1 superfamily and plays a
      critical role in the cellular proliferation, differentiation and elaboration of
      matrix pivotal to cutaneous wound healing. Smad3 antisense oligonucleotides
      (ASOs) impregnated polyelectrolyte complex (PEC) containing chitosan and sodium
      alginate was prepared for accelerated wound healing. Physicochemical properties
      of PEC were characterized by zeta potential, scanning electron microscopy and
      bioadhesive test. Full-thickness, excisional wounds were made on the dorsum of
      C57BL6 mice. Then, smad3 ASOs-PEC, PEC alone, smad3 ASOs and gauze dressing were
      applied to determine concentration of TGF-beta1 and collagen in tissues and
      observe the wound contraction and histology of tissues. Zeta potentials and
      bioadhesive strengths of ASOs-PEC were increased as the chitosan ratio in PEC. In
      smad3 ASOs-PEC, the healing process suggested by wound closure and histological
      observation was faster than other groups because collagen contents increased and
      level of TGF-beta1 decreased. These results demonstrate that the smad3 ASOs-PEC
      composed of chitosan and sodium alginate could be applied for accelerated wound
      healing.

PMID- 18829101
TI  - Silk-functionalized titanium surfaces for enhancing osteoblast functions and
      reducing bacterial adhesion.
AB  - It would be ideal to have implants which can simultaneously inhibit bacterial
      adhesion and promote osteoblast functions. In this work, titanium surfaces were
      modified with poly(methacrylic acid) (P(MAA)) followed by immobilization of silk
      sericin. Firstly a trichlorosilane coupling agent, which is an atom transfer
      radical polymerization (ATRP) initiator, was immobilized on the oxidized titanium
      surface to facilitate the surface-initiated ATRP of methacrylic acid sodium salt
      (MAAS). The pendant carboxyl end groups of the grafted and partially protonated
      MAA chains were subsequently coupled with silk sericin via carbodiimide
      chemistry. The functionalized Ti surfaces were characterized by X-ray
      photoelectron spectroscopy, and assayed for osteoblast cell functions and
      bacterial adhesion. The covalently immobilized MAA brushes significantly reduce
      the adhesion of the two bacterial strains (Staphylococcus aureus and
      Staphylococcus epidermidis) tested. The silk sericin-immobilized surfaces, at the
      same time, promote osteoblast cells' adhesion, proliferation, and alkaline
      phosphatase activity. Thus, the P(MAA) and silk sericin functionalized Ti
      surfaces have potential applications combating biomaterial-centered infection and
      promoting osseointegration.

PMID- 18829102
TI  - Cationic micelles self-assembled from cholesterol-conjugated oligopeptides as an
      efficient gene delivery vector.
AB  - Cholesterol-conjugated H(5)R(10) and H(10)R(10) oligopeptides (HR15-Chol and HR20
      Chol) were designed and synthesized. These amphiphilic oligopeptides were able to
      self-assemble into cationic micelles in aqueous solution at low concentrations,
      and their critical micelle concentrations in sodium acetate buffer (20mM, pH 5.0)
      were 17.8 and 28.2mg/L respectively. The micelle formation was further evidenced
      via SEM and dynamic light scattering analyses. The average hydrodynamic size of
      HR15-Chol and HR20-Chol micelles was about 425 and 435 nM in diameter with zeta
      potential of 64 and 66 mV respectively. The formation of micelles increased local
      concentration of cationic charge, leading to higher DNA binding efficiency as
      compared to the control peptides HR15 and HR20. The minimum size observed for
      HR15-Chol/DNA and HR20-Chol/DNA complexes was about 175-176 nM, and the maximum
      zeta potential was around 61-62 mV. In comparison, HR15 and HR20 formed DNA
      complexes with a similar size but significantly lower zeta potential (i.e. about
      31-40 mV). In particular, after being challenged by DMEM medium, the size of
      peptide/DNA complexes was increased significantly and their surface charge was
      neutralized. Nevertheless, the size of the micelle/DNA complexes formed from HR15
      Chol and HR20-Chol was still about 200 nM with positive charge of around 20 mV at
      high N/P ratios. The micelles induced much higher overall gene expression (i.e.
      luciferase expression) levels than the peptides in both HepG2 and HEK293 cell
      lines. Increasing the histidine residue from 0 to 5 to 10 further increased gene
      expression efficiency. In particular, HR20-Chol micelles yielded 95% GFP-positive
      HepG2 cells at N/P 50, much higher than that induced by PEI at its optimal N/P
      ratio (i.e. 10), which was 6.8%. In 4T1 cells, HR20-Chol induced 2 times higher
      luciferase expression level than PEI at their optimal N/P ratios. Moreover, HR20
      Chol micelle/DNA complexes were less cytotoxic than PEI/DNA complexes. These
      micelles may be a promising carrier for delivery of therapeutic genes.

PMID- 18829103
TI  - Adhesive substrate-modulation of adaptive immune responses.
AB  - While it is well-known that adsorbed proteins on implanted biomaterials modulate
      inflammatory responses, modulation of dendritic cells (DCs) via adhesion
      dependent signaling has only been begun to be characterized. In this work, we
      demonstrate that adhesive substrates elicit differential DC maturation and
      adaptive immune responses. We find that adhesive substrates support similar
      levels of DC adhesion and expression of stimulatory and co-stimulatory molecules.
      Conversely, DC morphology and differential production of pro- and anti
      inflammatory cytokines (IL-12p40 and IL-10, respectively) is adhesive substrate
      dependent. For example, DCs cultured on collagen and vitronectin substrates
      generate higher levels of IL-12p40, whereas DCs cultured on albumin and serum
      coated tissue culture-treated substrates produce the higher levels of IL-10
      compared to other substrates. Additionally, our results suggest substrate
      dependent trends in DC-mediated allogeneic CD4(+) T-cell proliferation and T
      helper cell type responses. Specifically, we show that substrate-dependent
      modulation of DC IL-12p40 cytokine production correlates with CD4(+) T-cell
      proliferation and T(h)1 type response in terms of IFN-gamma producing T-helper
      cells. Furthermore, our results suggest substrate-dependent trends in DC-mediated
      stimulation of IL-4 producing T-cells, but this T(h)2 type response is not
      dependent on DC production of IL-10 cytokine. This work has impact in the
      rational design of biomaterials for diverse applications such as tissue
      engineered constructs, synthetic particle-based vaccines and the ex vivo culture
      of DCs for immunotherapies.

PMID- 18829104
TI  - Maternal di-(2-ethylhexyl)-phthalate exposure influences essential fatty acid
      homeostasis in rat placenta.
AB  - Maintaining essential fatty acid (EFA) homeostasis during pregnancy is critical
      for fetal development. As the organ that controls the maternal-to-fetal supply of
      nutrients, the placenta plays a significant role in guiding EFA transfer to the
      fetus. Many EFA homeostasis proteins are regulated by peroxisome proliferator
      activated receptors (PPARs). The metabolites of di-(2-ethylhexyl)-phthalate
      (DEHP), a ubiquitous environmental contaminant, might influence EFA homeostasis
      via trans-activation of PPARs with subsequent downstream effects on EFA
      transporters and enzymes. To investigate DEHP's effect on placental/fetal EFA
      homeostasis, female Sprague-Dawley rats were orally gavaged with either vehicle
      or DEHP at 750 or 1500 mg/kg/day from gestational day (GD) 0 to GD 19. Changes in
      the expression of several EFA homeostasis regulating proteins were determined in
      the junctional (JXN) and labyrinthine (LAB) zones of the placenta, including PPAR
      isoforms (alpha, beta and gamma), fatty acid translocase (FAT/CD36), fatty acid
      transport protein 1 (FATP1), plasma membrane fatty acid binding protein (FABPpm),
      heart cytoplasmic fatty acid binding protein (HFABP), cytochrome P450 (CYP) 4A1,
      and cyclooxygenase (COX)-1 and -2. Additionally, effects of DEHP maternal
      exposure on the placental transfer and fetal distribution of representative EFAs,
      arachidonic acid (AA) and docosahexaenoic acid (DHA), and the placental
      production of prostaglandins (PGs) were investigated. Expression of PPARalpha,
      PPARgamma, FAT/CD36, FATP1, HFABP and CYP4A1 was up-regulated in JXN and/or LAB
      while COX-2 was down-regulated in JXN. PPARbeta, FABPpm, and COX-1 demonstrated
      variable expression. Reduced directional maternal-to-fetal placental transfer and
      altered fetal distribution of AA and DHA were observed in concordance with a
      decreased total placental PG production. These results correlate with previous in
      vitro data, suggesting that DEHP could influence placental EFA homeostasis with
      potential downstream effects in the developing fetus.

PMID- 18829105
TI  - Differential stimulatory effects of cannabinoids on VIP release and NO synthase
      activity in synaptosomal fractions from rat ileum.
AB  - Cannabinoid-1 (CB1) and CB2 receptors are present on neurons of the enteric
      nervous system. Our aim was to study whether cannabinoid receptor activation is
      involved in the regulation of VIP release and NO synthesis in isolated fractions
      of nerve terminals from rat ileum. VIP was measured by RIA and NO synthesis was
      analyzed using a L-[3H]arginine assay. Anandamide stimulated VIP release (basal:
      245.9+/-12.4pg/mg, 10(-6)M: 307.6+/-11.7pg/mg, [n=6, P<0.05], 10(-7)M: 367.0+/
      26.1pg/mg, [n=6, P<0.01]). The cannabinoid receptor agonist WIN 55,212-2 had
      similar effects (basal: 250.5+/-37.4pg/mg, 10(-6)M: 320.9+/-34.7pg/mg; [n=4,
      P<0.05]). The stimulatory effect of anandamide was blocked by the selective CB2
      receptor antagonist, SR144528 (10(-7)M) (anandamide 10(-6)M: 307.6+/-11.7pg/mg;
      +SR144528: 249.0+/-26.3pg/mg, [n=6, P<0.05]), whereas the selective CB1 receptor
      antagonist SR141716 A had no effect. NO synthesis was stimulated by anandamide
      ([fmol/mg/min] basal: 0.08+/-0.01, 10(-6)M: 0.16+/-0.03; 10(-7)M: 0.13+/-0.02,
      n=4, P<0.05) and WIN 55,212-2 ([fmol/mg/min] basal: 0.05+/-0.01, 10(-6)M: 0.1+/
      0.02, n=4, P<0.05). The anandamide reuptake inhibitor, AM 404 increased basal NOS
      activity ([fmol/mg/min] control: 0.1+/-0.04, 10(-6)M: 0.28+/-0.08, n=7, P<0.05).
      The stimulatory effect of anandamide on NO synthase was not antagonized by
      antagonists at the CB1, CB2 or TRPV1 receptor, respectively. In conclusion, in
      enteric nerves anandamide stimulates VIP release by activation of a CB2 receptor
      specific pathway, while the stimulation of NO production suggests the existence
      of an additional type of cannabinoid receptor in the enteric nervous system.

PMID- 18829106
TI  - Oral arsenic treatment of leukemia and the risk of porphyria.

PMID- 18829107
TI  - Quantitative monitoring of the T315I mutation in patients with chronic myeloid
      leukemia (CML).
AB  - Tyrosine kinase inhibitors (TKIs) have dramatically improved the treatment of
      chronic myeloid leukemia (CML). However, resistances are occasionally observed,
      mainly due to mutations within the BCR-ABL kinase domain. The T315I substitution
      confers complete resistance to TKIs commonly used in clinical practice. In the
      present study, we used an allele-specific quantitative-RT-PCR to perform a
      molecular follow-up of BCR-ABL transcripts harboring the T315I mutation. We
      retrospectively quantified BCR-ABL315I mRNA in five patients who acquired the
      T315I mutation. Our results highlight the relevance of allele-specific Q-RT-PCR
      experiments for the monitoring of mutated BCR-ABL transcripts and suggest that
      the kinetics of emergence of T315I mutant mRNA is influenced by the stage of the
      disease and the presence of previous BCR-ABL kinase domain mutations.

PMID- 18829108
TI  - Bortezomib in combination with dexamethasone for a young multiple myeloma with
      t(8; 14).

PMID- 18829109
TI  - Unbalanced whole-arm translocation der(5;19)(p10;q10) is a novel and recurrent
      cytogenetic aberration in myelodysplastic syndrome.
AB  - We describe here two cases of myelodysplastic syndrome (MDS) with a novel
      unbalanced translocation der(5;19)(p10;q10). Both patients had complex karyotypes
      including der(5;19) accompanied by an extra chromosome 19, resulting in deletion
      of the whole long arm of chromosome 5. Furthermore, these patients presented
      several common clinical and hematological characteristics: MDS subtypes as
      refractory anemia with excess of blasts (RAEB)-1 or RAEB-2, marked anemia and
      thrombocytopenia without neutropenia, leukoerythroblastosis, trilineage dysplasia
      with prominent dyserythropoiesis, CD7 expression in blasts, and association with
      abnormalities of chromosomes 6, 17 and 18. These findings indicate that
      der(5;19)(p10;q10) may play a crucial role in the pathogenesis of high-risk MDS
      as a rare but recurrent translocation.

PMID- 18829110
TI  - Aberrant promotor methylation in MDS hematopoietic cells during in vitro lineage
      specific differentiation is differently associated with DNMT isoforms.
AB  - Aberrant promoter methylation may contribute to the hematopoietic disturbances in
      myelodysplastic syndromes (MDS). To explore a possible mechanism, we therefore
      analyzed expression of DNA methyltransferase (DNMT) subtypes kinetics and
      aberrant promoter methylation of key regulatory genes during MDS hematopoiesis.
      An in vitro model of MDS lineage-specific hematopoiesis was generated by
      culturing CD34+ cells from healthy donors (n=7) and MDS patients (low-risk:
      RA/n=6, RARS/n=3; high-risk: RAEB/n=4, RAEB-T/n=2) with EPO, TPO and GCSF.
      Promoter methylation analysis of key genes involved in the control of apoptosis
      (p73, survivin, DAPK), DNA-repair (hMLH1), differentiation (RARb, WT1) and cell
      cycle control (p14, p15, p16, CHK2) was performed by methylation specific PCR of
      bisulfite-treated genomic DNA. Expression of DNMT1, DNMT3a and DNMT3b was
      analyzed and correlated with gene promoter methylation for each lineage at
      different time points. DNMT expression (all isoforms) was increased during
      thrombopoiesis whereas elevated DNMT1 level were seen during erythropoiesis.
      Associations between aberrant promoter methylation and DNMT expression were found
      in high-risk MDS for all lineages and during erythropoiesis. Hypermethylation of
      p15, p16, p73, survivin, CHK2, RARb and DAPK were associated with elevated DNMT
      isoform expression. No general overexpression of DNMT subtype was detected during
      MDS hematopoiesis. However a negative association of DNMT3a and 3b expression
      with MDS disease risk (IPSS) could be observed. Our data indicate that all
      mammalian DNMT isoforms may be involved in the aberrantly methylated phenotype in
      MDS but seem also to be essential for the differentiation of normal hematopoietic
      stem cells. In particular elevated DNMT1 expression may in particular contribute
      to ineffective erythropoiesis in MDS.

PMID- 18829111
TI  - Secretion of MMP-2 and MMP-9 induced by VEGF autocrine loop correlates with
      clinical features in childhood acute lymphoblastic leukemia.
AB  - In children with acute lymphoblastic leukemia (ALL), leukemic cells express
      several members of the VEGF family and the three VEGF receptors which, via an
      autocrine loop are responsible for secretion of MMP-2/-9. MMP activity and the
      presence of elements of the autocrine loop are correlated with clinical and
      prognostic parameters as follows: i) high basal MMP-9 activity with tumoral
      syndrome, ii) MMP-2 activity with treatment failure, iii) VEGFR-1/-3 co
      expression with high hemoglobin level and iv) expression of the VEGF-A 121
      isoform and favorable response to treatment. These data implicate autocrine VEGF
      induced secretion of MMP-2/-9 in the physiopathology of childhood ALL.

PMID- 18829112
TI  - Personality and community prevention teams: Dimensions of team leader and member
      personality predicting team functioning.
AB  - The predictors and correlates of positive functioning among community prevention
      teams have been examined in a number of research studies; however, the role of
      personality has been neglected. In this study, we examined whether team member
      and leader personality dimensions assessed at the time of team formation
      predicted local prevention team functioning 2.5-3.5 years later. Participants
      were 159 prevention team members in 14 communities participating in the PROSPER
      study of prevention program dissemination. Three aspects of personality,
      aggregated at the team level, were examined as predictors: Openness to
      Experience, Conscientiousness, and Agreeableness. A series of multivariate
      regression analyses were performed that accounted for the interdependency of five
      categories of team functioning. Results showed that average team member Openness
      was negatively, and Conscientiousness was positively linked to team functioning.
      The findings have implications for decisions about the level and nature of
      technical assistance support provided to community prevention teams.

PMID- 18829113
TI  - Optochiasmal apoplexy due to a cavernoma.

PMID- 18829114
TI  - Australian firefighters' exposure to air toxics during bushfire burns of autumn
      2005 and 2006.
AB  - Bushfire fighting is a hazardous occupation and control strategies are generally
      in place to minimize the hazards. However, little is known regarding
      firefighters' exposure to bushfire smoke, which is a complex mixture of toxic
      gases and particles. In Australia, during the prescribed burning season,
      firefighters are likely to be exposed on a regular basis to bushfire smoke, but
      whether these exposures affect health has yet to be determined. There are a
      number of factors that govern whether exposure to smoke will result in short-term
      and/or long-term health problems, including the concentrations of air pollutants
      within the breathing zone of the firefighter, the exposure duration, and health
      susceptibility of the individual, especially for pre-existing lung or heart
      disease. This paper presents measurements of firefighters' personal exposure to
      bushfire smoke, the first step within a risk management framework. It provides
      crucial information on the magnitude, extent and frequency of personal exposure
      to bushfire smoke for a range of typical scenarios. It is found that the primary
      air toxics of concern are carbon monoxide (CO), respirable particles and
      formaldehyde. Also, work activity is a major factor influencing exposure with
      exposure standards (both average and short-term limits) likely to be exceeded for
      activities such as suppression of spot fires, holding the fireline, and
      patrolling at the edge of a burn area in the urban-rural interface.

PMID- 18829115
TI  - Proteolytic processing of polyphenol oxidase from plants and fungi.
AB  - Polyphenol oxidase (PPO), a metalloenzyme containing a type-3 copper center, is
      produced by many species of plants, fungi, and bacteria. There is great
      variability in the subunit molecular mass reported for PPO, even from a single
      species. In some cases, experimental evidence (usually protein sequencing by
      Edman degradation) indicates that the variability in molecular mass for PPO from
      a given species is the result of proteolytic processing at the N and/or C-termini
      of the protein. In order to identify specific sequence regions where proteolysis
      occurs in PPO from most species, the experimentally established N and C-termini
      of these proteolyzed enzymes were compared to the protein sequences of other PPOs
      for which the N and C-termini have not been established by protein sequencing
      methods. In all cases the N-terminal proteolysis sites were located prior to a
      conserved arginine residue, and the C-terminal proteolysis sites were located
      following a conserved tyrosine motif. Based on the sites of proteolysis,
      molecular masses were calculated for the enzymes, and the calculated values were
      used to rationalize the varying molecular masses reported in the literature. To
      determine the structural implications of N and C-terminal proteolysis, the
      proteolysis sites were related to the two available PPO structures: Ipomoea
      batatas catechol oxidase and Streptomyces castaneoglobisporus tyrosinase. A
      structural "core" region that appears to be essential for structural stability
      and enzymatic activity was identified.

PMID- 18829116
TI  - Long-term protection of hepatitis B vaccine 18 years after vaccination.
AB  - INTRODUCTION: This is the third evaluation study of the hepatitis B virus (HBV)
      vaccination program, initiated in 1989 in Saudi Arabia. AIMS: This study sought
      to assess the efficacy and long-term protection of the hepatitis B vaccine among
      Saudi adolescents. METHODS: School students between the ages of 16 and 18 years
      were randomly chosen from high endemic (Aseer), intermediate endemic (Madinah),
      and low endemic (Al-Qaseem) areas of the country. Hepatitis B surface antigen
      (HBsAg), hepatitis B core IgG antibody (anti-HBc), and hepatitis B surface
      antibody (anti-HBs) were measured using standard techniques. RESULTS: A total of
      1355 students (689 males and 666 females) were selected randomly from the three
      areas. No cases of positive HBsAg or anti-HBc were detected among the study
      population. Five hundred and ten students (38%) showed protective anti-HBs titers
      (>/= 10mIU/ml), while 528 (39%) students had undetectable anti-HBs titers (<1
      mIU/ml). CONCLUSIONS: This study shows the excellent efficacy of the HBV
      vaccination program in Saudi Arabia 18 years after its launch. Based on this
      study and others, a booster dose for the adult population appears to be
      unnecessary.

PMID- 18829117
TI  - Dimensions of postpartum psychiatric distress: preliminary evidence for
      broadening clinical scope.
AB  - BACKGROUND: Perinatal psychiatric disturbances afflict a significant number of
      women sometimes with tragic consequence. Yet, the range and characteristics of
      these disturbances are poorly understood. The goals of this research were to
      characterize a broader range of postpartum psychiatric symptoms and to identify
      their inherent structure using exploratory factor analysis (EFA). METHODS: An
      Internet-based survey with 142 Likert-type questions, covering nine dimensions of
      postpartum mental health was constructed and posted on women's health websites.
      Data collected from 215 respondents was analyzed in three steps: (1) inter-item
      correlations were used to reduce the total number of variables by eliminating
      items that provided redundant information; (2) an EFA using a principal
      components extraction and VARIMAX rotation was performed and factors loading with
      Eigenvalues >1.0 were retained; (3) internal consistency was measured with
      Cronbach's alpha. RESULTS: The 10 factors retained accounted for 58% of the
      variance and included: mental status (28%), psychoticism/morbid thoughts (6%),
      generalized anxiety (6%), panic (3%), guilt/self-criticism (3%), compulsive
      behavior (3%), hyper-vigilance (2%), contentment (2%), negative body-image (2%),
      and manic behavior (2%). There was strong (>0.8) internal consistency in all but
      the mania factor (0.6). LIMITATIONS: The study was retrospective and respondent
      demographics were homogeneous. CONCLUSION: Postpartum psychiatric disturbances
      are not limited to depressive symptoms. In the current study, cognitive
      difficulties, psychotic-morbid thoughts and anxiety symptoms accounted for the
      preponderance of variance while depressive symptoms did not form a cohesive
      factor and accounted for minimal variance. These results suggest postpartum
      screening tools should assess a broader array of symptoms.

PMID- 18829118
TI  - Histamine bronchoprovocation does not affect bronchoalveolar lavage fluid
      cytology, gene expression and protein concentrations of IL-4, IL-8 and IFN-gamma.
AB  - In diagnosing inflammatory airway disease (IAD) in performance horses, a
      histamine bronchoprovocation (HBP) test is often performed. In previously
      published studies, HBP is usually undertaken prior to cytological examination of
      the bronchoalveolar lavage (BAL) cells. The purpose of this study was to
      determine if HBP alters (1) the total nucleated cell numbers and distribution in
      BAL fluid (BALF) and (2) the mRNA and protein concentrations of selected
      cytokines in BAL cells and BALF, respectively. BALF was initially collected
      endoscopically from the right middle or diaphragmatic lung lobe in eight healthy
      young Standardbred horses. Five to six days later, HBP was performed by
      aerosolization of histamine (8mg) over a 2min period. BALF was again collected
      within 2-4h of the HBP from the left middle or diaphragmatic lung lobe. In both
      samples, total and differential WBC counts were obtained. The gene expressions of
      interleukin-4 (IL-4), IL-8, interferon-gamma (IFN-gamma) and beta-actin in BAL
      cells were measured using real-time RT-PCR. The cytokine protein concentrations
      were measured in the BALF using ELISA. HBP was not associated with either a
      change in the total BAL cell number or in the distribution of the BAL cells. BAL
      cell expression of IL-4, IL-8 and IFN-gamma, detected in all samples with the
      exception of IL-4 in one horse (post-HBP), was not altered as a result of HBP.
      HBP was not associated with a significant change in IL-8 or IFN-gamma
      concentrations in the BALF. IL-4 protein was undetectable in BALF either prior to
      or following HBP. We conclude that HBP can precede BALF collection performed
      within 2-4h of the former without affecting selected parameters analysed in the
      BAL cells or BALF.

PMID- 18829119
TI  - Blockade of cytosolic phospholipase A2 alpha prevents experimental autoimmune
      encephalomyelitis and diminishes development of Th1 and Th17 responses.
AB  - Cytosolic phospholipase A2 alpha (cPLA2 alpha) is the rate-limiting enzyme for
      release of arachidonic acid, which is converted primarily to prostaglandins via
      the cyclooxygenase (COX) 1/2 pathways, and leukotrienes via the 5-lipoxygenase
      (LO) pathway. We utilized inhibitors of cPLA2 alpha, COX-1/2 and 5-LO to
      determine the potential roles of these enzymes in development of experimental
      autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS).
      Blocking cPLA2 alpha prevented EAE development and greatly reduced antigen
      induced production of Th1-type cytokines and IL-17. Blocking COX-1/2 delayed
      onset and reduced severity of EAE, and reduced production of Th1-type cytokines,
      but not IL-17. Blocking 5-LO delayed onset and reduced cumulative severity of
      EAE, but did not reduce production of Th1-type cytokines or IL-17. Finally,
      blockade of cPLA2 alpha from the onset of clinical EAE reduced duration of EAE
      relapses. Therefore, cPLA2 alpha represents a potential therapeutic target for
      treatment of MS.

PMID- 18829120
TI  - Developing a list of reference chemicals for testing alternatives to whole fish
      toxicity tests.
AB  - This paper details the derivation of a list of 60 reference chemicals for the
      development of alternatives to animal testing in ecotoxicology with a particular
      focus on fish. The chemicals were selected as a prerequisite to gather
      mechanistic information on the performance of alternative testing systems, namely
      vertebrate cell lines and fish embryos, in comparison to the fish acute lethality
      test. To avoid the need for additional experiments with fish, the U.S. EPA
      fathead minnow database was consulted as reference for whole organism responses.
      This database was compared to the Halle Registry of Cytotoxicity and a collation
      of data by the German EPA (UBA) on acute toxicity data derived from zebrafish
      embryos. Chemicals that were present in the fathead minnow database and in at
      least one of the other two databases were subject to selection. Criteria included
      the coverage of a wide range of toxicity and physico-chemical parameters as well
      as the determination of outliers of the in vivo/in vitro correlations. While the
      reference list of chemicals now guides our research for improving cell line and
      fish embryo assays to make them widely applicable, the list could be of benefit
      to search for alternatives in ecotoxicology in general. One example would be the
      use of this list to validate structure-activity prediction models, which in turn
      would benefit from a continuous extension of this list with regard to physico
      chemical and toxicological data.

PMID- 18829121
TI  - Social interactions, predation behaviour and fast start performance are affected
      by ammonia exposure in brown trout (Salmo trutta L.).
AB  - In fish, fast starts are brief, sudden accelerations during predator-prey
      encounters. They serve for escape and predation and are therefore ecologically
      important movements. Fast starts are generated by glycolytic muscle performance
      and are influenced by many internal and external factors. It is known that
      ammonia pollution has a major effect on the glycolytic muscle action, thus
      creating conditions in which fast start performance might be reduced and
      predation rates altered. Therefore, escape response and predation strikes were
      investigated in brown trout (Salmo trutta) of 10 and 20 cm body length exposed to
      an elevated (1 mg l(-1)) ammonia concentration for 24 and 96 h. Various locomotor
      and behavioural variables were measured. In C-starts, i.e. an escape start where
      the fish bends into a C-shaped position, ammonia exposure had no effect on
      response latency. After 96 h of exposure, cumulative distance, maximum swimming
      speed and turning radius of the prey were all significantly reduced and the
      escape went in no definite direction. The effect of ammonia exposure was more
      pronounced in large fish than in small fish. Predation strikes were also
      affected. Distance, speed and turning radius were significantly lower in exposed
      fish. Agonistic behaviour of dominant fish was significantly reduced and fish
      spent more time resting. Predator behaviour was also altered and the number of
      prey captured was reduced. This study shows that ammonia exposure affects brown
      trout escape response mainly through a reduction in fast start velocity and
      through an impairment of directionality. Thus, in addition to a reduced strength
      of the response, ammonia exposure could also reduce the fish's elusiveness facing
      a predator. Predation rate and social interactions are disrupted and predator
      prey relationships could be altered.

PMID- 18829122
TI  - The study of the age of becoming edentulous in the last 20 years in Turkey.
AB  - The aim of this study was to determine the age of becoming edentulous and make a
      comparison between the patients examined in 1987 and in 2007 at the Dental
      School, University of Marmara in Istanbul, Turkey. A total of 680 patients (336
      in 1987 and 344 in 2007) visiting the Dental School were examined. Some of the
      patients had just their teeth drawn, or had already became edentulous before, and
      were sent to the Department of Prosthodontics, for prosthodontic treatment of
      their edentulous mandible or maxilla. Some of the patients have few teeth and
      they were extracted at the Department of Oral and Maxillofacial Surgery, they
      became edentulous. The age of the patients that they first become edentulous and
      begin to use complete denture was determined. The patients grouped according to
      their age, sex and being completely edentulous or edentulous in one jaw. Fisher's
      exact test was performed during the evaluation of quantitative data. Statistical
      significance level was established at p<0.05. Between 1987 and 2007, a more than
      50% decrease was observed in the number of the patients who were completely
      edentulous or edentulous only in one jaw. This observation is one of the
      indications of development of patients' care and improvement in the state of
      mouth health in Turkey during the last 20 years.

PMID- 18829123
TI  - A 10-year follow-up study on subjective well-being and relationships to person
      environment (P-E) fit and activity of daily living (ADL) dependence of older
      Swedish adults.
AB  - In order to investigate how well-being and ill health is affected by the process
      of aging, the main aim was to investigate these self-perceived aspects of health
      over a 10-year period among older Swedish adults. The aim was also to study how
      these aspects correlated with objectively assessed functional limitations, use of
      mobility device, person-environment (P-E) fit (also denoted accessibility),
      problems in housing, and activity of daily living (ADL) dependence. Using the
      Swedish national population register, a baseline sample of persons aged 75-84
      years was identified. Out of the 133 participants at baseline (1994), the 31
      participants still available 10 years later were included. The data were
      collected by means of interview and observation at home visits. Overall, the
      participants rated their subjective well-being as high and a stable prevalence of
      ill-health symptoms over time was reported. Changes in subjective well-being as
      related to changes in functional aspects seem to mainly occur earlier in the
      aging process, while as time goes by these relations weaken. ADL dependence,
      however, is more influential in more advanced age. The results confirm the
      complexity of the construct of health. A main contribution is that the results
      shed light on the importance of taking the impact of environmental factors into
      consideration.

PMID- 18829124
TI  - Unfair inequalities in health and health care.
AB  - Inequalities in health and health care are caused by different factors. Measuring
      "unfair" inequalities implies that a distinction is introduced between causal
      variables leading to ethically legitimate inequalities and causal variables
      leading to ethically illegitimate inequalities. An example of the former could be
      life-style choices, an example of the latter is social background. We show how to
      derive measures of unfair inequalities in health and in health care delivery from
      a structural model of health care and health production: "direct unfairness",
      linked to the variations in medical expenditures and health in the hypothetical
      distribution in which all legitimate sources of variation are kept constant;
      "fairness gap", linked to the differences between the actual distribution and the
      hypothetical distribution in which all illegitimate sources of variation have
      been removed. These two approaches are related to the theory of fair allocation.
      In general they lead to different results. We propose to analyse the resulting
      distributions with the traditional apparatus of Lorenz curves and inequality
      measures. We compare our proposal to the more common approach using concentration
      curves and analyse the relationship with the methods of direct and indirect
      standardization. We discuss how inequalities in health care can be integrated in
      an overall evaluation of social inequality.

PMID- 18829125
TI  - Enhanced bactericidal effect of enterocin AS-48 in combination with high
      intensity pulsed-electric field treatment against Salmonella enterica in apple
      juice.
AB  - The effect of the broad spectrum cyclic antimicrobial peptide enterocin AS-48
      combination with high-intensity pulsed-electric field (HIPEF) treatment (35
      kV/cm, 150 Hz, 4 micros and bipolar mode) was tested on Salmonella enterica CECT
      915 in apple juice. A response surface methodology was applied to study the
      bactericidal effects of the combined treatment. The process variables were AS-48
      concentration, temperature, and HIPEF treatment time. While treatment with
      enterocin AS-48 alone up to 60 microg/ml had no effect on the viability of S.
      enterica in apple juice, an increased bactericidal activity was observed in
      combination with HIPEF treatments. Survival fraction was affected by treatment
      time, enterocin AS48 concentration and treatment temperature. The combination of
      100 micros of HIPEF treatment, 30 microg/ml of AS-48, and temperature of 20
      degrees C resulted in the lowest inactivation, with only a 1.2-log reduction. The
      maximum inactivation of 4.5-log cycles was achieved with HIPEF treatment for 1000
      micros in combination with 60 microg/ml of AS-48 and a treatment temperature of
      40 degrees C. Synergism between enterocin AS-48 and HIPEF treatment depended on
      the sequence order application, since it was observed only when HIPEF was applied
      in the presence of previously-added bacteriocin. The combined treatment could
      improve the safety of freshly-made apple juice against S. enterica transmission.

PMID- 18829126
TI  - Foot ulcer risk and location in relation to prospective clinical assessment of
      foot shape and mobility among persons with diabetes.
AB  - AIMS: We assessed baseline clinical foot shape for 2939 feet of diabetic subjects
      who were monitored prospectively for foot ulceration. METHODS: Assessments
      included hammer/claw toes, hallux valgus, hallux limitus, prominent metatarsal
      heads, bony prominences, Charcot deformity, plantar callus, foot type, muscle
      atrophy, ankle and hallux mobility, and neuropathy. Risk factors were linked to
      ulcer occurrence and location via a Cox proportional hazards model. RESULTS:
      Hammer/claw toes (hazard ratio [HR] (95% confidence interval [CI])=1.43 (1.06,
      1.94) p=0.02), marked hammer/claw toes (HR=1.77 (1.18, 2.66) p=0.006), bony
      prominences (HR=1.38 (1.02, 1.88), p=0.04), and foot type (Charcot or drop foot
      vs. neutrally aligned) (HR=2.34 (1.33, 4.10), p=0.003) were significant risk
      factors for ulceration adjusting for age, body mass index, insulin medication,
      ulcer history and amputation history. With adjustment for neuropathy only
      hammer/claw toes (HR=1.40 (1.03, 1.90), p=0.03) and foot type (HR=1.76 (1.04,
      3.04), p=0.05) were significantly related to ulceration. However, there was no
      relationship between ulcer location and foot deformity. CONCLUSIONS: Certain foot
      deformities were predictive of ulceration, although there was no relationship
      between clinical foot deformity and ulcer location.

PMID- 18829127
TI  - Type 2 diabetes but not coronary atherosclerosis is an independent determinant of
      impaired mobility in angiographied coronary patients.
AB  - AIMS: We aimed at determining the associations of type 2 diabetes (T2DM) and of
      angiographically determined coronary artery disease (CAD) with impaired mobility.
      METHODS: We enrolled 747 consecutive patients undergoing coronary angiography for
      the evaluation of stable CAD. Mobility was assessed by the standardized timed-up
      and-go (TUG) test, a functional test of physical performance. RESULTS: Mobility
      was impaired (TUG time >10s) in 199 (26.6%) patients. The proportion of subjects
      with impaired mobility was higher among patients with T2DM than among non
      diabetic individuals (40.2% vs. 22.0%; p<0.001), whereas it did not differ
      significantly between patients with significant coronary stenoses >or=50% and
      those without such lesions (p=0.802). Multivariate adjustment in logistic
      regression analyses confirmed that T2DM (adjusted odds ratio (OR)=2.05 [95% CI
      1.35-3.11]; p=0.001) but not the presence of significant coronary stenoses
      (adjusted OR=0.81 [0.55-1.21]; p=0.306) was independently associated with
      impaired mobility. CONCLUSIONS: T2DM but not coronary atherosclerosis is an
      independent determinant of impaired mobility in the high risk population of
      angiographied coronary patients. Mobility enhancing exercise programs are needed
      for diabetic coronary patients.

PMID- 18829128
TI  - The effect of an area-based intervention on breastfeeding rates in Victoria,
      Australia.
AB  - OBJECTIVES: Best Start is an area-based early childhood intervention where
      projects are developed and implemented through a community partnership. A core
      tenet of the initiative is that implementing projects through a partnership
      generates greater value than would be expected if projects were undertaken
      independently by partner members. In this study we examine whether: (1) Best
      Start is effective in increasing the proportion of infants being fully breastfed
      at 3 months and 6 months. (2) The quality of community partnerships is a
      potential mechanism for change. METHODS: Best Start was implemented in Victoria,
      Australia. The study examined breastfeeding rates before and after Best Start in
      sites with Best Start breastfeeding projects compared to the rest of state. The
      relationship between partnership quality scores and breastfeeding percentages was
      also examined. Both analyses controlled for socioeconomic and demographic
      differences and clustering by area. RESULTS: Best Start targeted some of the most
      socially disadvantaged communities in Victoria. In the 3 years of its operation,
      the rates of fully breastfeeding at 3 months (OR 1.30, 95% CI 1.14-1.47) and 6
      months (OR 1.33, 95% CI 1.1-1.61) increased in Best Start sites compared to the
      rest of the state. Quality of partnership scores was positively associated with
      increased percentages of fully breastfeeding (3 months=OR 1.03, 95% CI 1.01-1.06;
      6 months=OR 1.03, 95% CI 0.98-1.08). CONCLUSIONS: These results suggest that area
      based interventions are effective in increasing percentages of fully
      breastfeeding. The study also supported the idea that developing quality
      community partnerships had a positive influence on their success.

PMID- 18829129
TI  - Making performance indicators work: the experience of using consensus indicators
      for external assessment of health and social services at regional level in Spain.
AB  - OBJECTIVES: To describe a methodology and the results of projects combining
      consensus processes for indicator development with methods of external assessment
      of health and social services. METHODS: Our methodology can be characterized by a
      four-step approach: (1) stakeholder involvement and creating an enabling
      environment, (2) using standardized consensus methods for indicator development,
      (3) using rigorous external evaluation methods to assess results and (4)
      developing and implementing quality improvement initiatives. We describe each
      step in detail and discuss factors of success and pitfalls based on our
      experience of applying the methodology in 648 health/social centres and reviewing
      overall 68,616 case records. RESULTS: We observe in four sectors (assisted
      living, elderly health care, care for people with drug abuse problems, and care
      for abused woman) improvements in overall quality improvement rates, ranging from
      9.5% to 65.6%. Improvements in overall rates are accompanied by reduction in
      range of up to 48.8. CONCLUSIONS: The conscientious setting up of an enabling
      environment and the systematic involvement of professionals in designing
      indicators and setting standards is a key to improving performance. Our research
      may entail lessons for policy makers on the current debate on pay for performance
      models.

PMID- 18829130
TI  - Engaging patients as safety partners: some considerations for ensuring a
      culturally and linguistically appropriate approach.
AB  - Engaging patients as 'safety partners' with health service providers to help
      identify and rectify preventable adverse events in health care is being
      increasingly accepted in the USA, Australia, and elsewhere as a promising
      strategy to improve patient safety outcomes. The implications of this trend for
      patients and families of minority cultural and language backgrounds have not,
      however, been comprehensively considered. In this article, attention is given to
      briefly exploring the notion of patient participation in health care and the
      problematic transposition of the concept into patient safety discourse. The
      importance of recognising and responding to the critical relationship between
      culture, language and patient safety outcomes, and the possible benefits and
      risks of engaging patients of minority ethnic backgrounds in safety partnership
      programs are explored. It is suggested that if patient safety
      engagement/partnership programs are to perform well in cross-cultural health care
      contexts, they need to be supported by research evidence and appropriately
      informed by the perspectives and experiences of patients and families/nominated
      carers from minority cultural and language backgrounds. They also need to be
      appropriately supported by culturally competent policies and practices across the
      entire health care system. The importance of robust internationally comparative
      research on this issue is highlighted.

PMID- 18829131
TI  - An architecture for online comparison and validation of processing methods and
      computerized guidelines in intensive care units.
AB  - Clinical decision support systems are a combination of software techniques to
      help the clinicians in their medical decision making process via functionalities
      ranging from basic signal analysis to therapeutic planning and computerized
      guidelines. The algorithms providing all these functionalities must be very
      carefully validated on real patient data and must be confronted to everyday
      clinical practice. One of the main problems when developing these techniques is
      the difficulty to obtain high-quality complete patient records, comprising data
      coming both from the biomedical equipment (high-frequency signals), and from
      numerous other sources (therapeutics, imagery, clinical actions, etc.). In this
      paper, we present an infrastructure for developing and testing such software
      algorithms. It is based on a bedside workstation where testing different
      algorithms simultaneously on real-time data is possible in the ward. It is
      completed by a collaborative portal enabling different teams to test their
      software algorithms on the same patient records, making comparisons and cross
      validations more easily.

PMID- 18829132
TI  - Isolation and characterization of ACC deaminase-producing fluorescent
      pseudomonads, to alleviate salinity stress on canola (Brassica napus L.) growth.
AB  - Salinity stress is of great importance in arid and semi-arid areas of the world
      due to its impact in reducing crop yield. Under salinity stress, the amount of 1
      aminocyclopropane-1-carboxylate (ACC), a precursor for ethylene production in
      plants, increases. Here, we conducted research under the hypothesis that isolated
      ACC deaminase-producing Pseudomonas fluorescens and Pseudomonas putida can
      alleviate the stressful effects of salinity on canola (Brassica napus L.) growth.
      The experiments were conducted in the Soil and Water Research Institute, Tehran,
      Iran. Seven experimental stages were conducted to isolate and characterize ACC
      deaminase-producing Pseudomonas fluorescens strains and to determine factors
      enhancing their growth and, consequently, their effects on the germination of
      canola seeds. Under salinity stress, in 14% of the isolates, ACC deaminase
      activity was observed, indicating that they were able to utilize ACC as the sole
      N-source. Bacterial strains differed in their ability to synthesize auxin and
      hydrogen cyanide compounds, as well as in their ACC deaminase activity. Under
      salinity stress, the rate of germinating seeds inoculated with the strains of ACC
      deaminase-producing Pseudomonas fluorescens and Pseudomonas putida, and seedling
      growth was significantly higher. These results indicate the significance of soil
      biological activities, including the activities of plant growth-promoting
      bacteria, in the alleviation of soil stresses such as salinity on plant growth.

PMID- 18829133
TI  - Perineuronal nets are largely unaffected in Alzheimer model Tg2576 mice.
AB  - Changes in the molecular organization of the extracellular matrix are key factors
      in neuropathology. We investigated aggrecan-based perineuronal nets (PNs) in
      relation to neurodegeneration and activation of glial cells in a transgenic mouse
      (Tg2576) model of Alzheimer's disease. The formation of amyloid plaques in the
      cerebral cortex occurred independently of the area-specific distribution of PNs.
      Matrix components were only affected in the core of plaques in advanced stages of
      pathology. PNs remained unchanged in the large marginal zone occupied by reactive
      astrocytic processes. We conclude that the aggrecan-based extracellular matrix of
      PNs is not enzymatically altered in peripheral plaque territories and is only
      removed after neuronal death.

PMID- 18829134
TI  - Vascular health risks and fMRI activation during a memory task in older adults.
AB  - Vascular problems increase Alzheimer's disease (AD) risk, but the nature of this
      relationship remains unclear. Older adults having genetic risk for AD show
      regionally increased functional magnetic resonance imaging (fMRI) activity during
      memory, possibly representing compensation for a genetically induced neural
      deficit. We investigated whether vascular health risks, which similarly could
      lead to neuropsychological deficits, also showed increased fMRI activity during a
      memory task performed by 30 cognitively intact, primarily normotensive older
      adults (mean age=61). Vascular risk measures included systolic blood pressure
      (sBP), body mass index (BMI), and total cholesterol. Higher sBP and BMI (but not
      total cholesterol) were significantly correlated with increased activation in
      posterior cingulate cortex and frontal, temporal, and parietal regions. In
      posterior cingulate and parietal cortices, these relationships were evident even
      within sBP and BMI ranges considered normal, and were independent of hippocampal
      volume. Our results are similar to those in prior AD risk research, and suggest
      that fMRI reveals an abnormal response to cognitive processes in cognitively
      intact older adults with increased vascular risk.

PMID- 18829135
TI  - Distinctive alterations of the cingulum bundle during aging and Alzheimer's
      disease.
AB  - Brain imaging studies have revealed frontal disruption during aging and parieto
      temporal disruption during Alzheimer's disease (AD). The present study aims at
      developing a specific method based on precise anatomical landmarks for assessing
      the integrity all along the course of the cingulum bundle, so as to determine if
      it presents the classical aging and AD dissociation. Five regions of interest
      (ROIs) were placed on fractional anisotropy (FA) maps all along the cingulum in
      15 young (Gyoung), 15 70-year-old (Gold), and 15 AD subjects (Galz). An age
      related decrease of FA occurred in the anterior part of the bundle. Moreover, a
      specific alteration of the supero-posterior region of the cingulum during AD was
      observed since mean FA values as well as mean number of fibers were significantly
      decreased in Galz compared to Gold and Gyoung. This multiple ROIs placement
      allows for revealing distinctive alterations of the cingulum bundle during aging
      and AD, which could constitute the anatomical basis for the distinctive
      functional disconnection recently described in the literature using functional
      connectivity at rest.

PMID- 18829136
TI  - Whole brain atrophy rate predicts progression from MCI to Alzheimer's disease.
AB  - For both clinical and research reasons, it is essential to identify which mild
      cognitive impairment (MCI) subjects subsequently progress to Alzheimer's disease
      (AD). The prediction may be facilitated by accelerated whole brain atrophy
      exhibited by AD subjects. Iterative principal component analysis (IPCA) was used
      to characterize whole brain atrophy rates using sequential MRI scans for 102 MCI
      subjects from the Kuopio University Hospital. We modelled the likelihood of
      progression to probable AD, and found that each additional percent of annualized
      whole brain atrophy rate was associated with a higher odds ratio (OR) of
      progression (OR=1.30, p=0.01, 95% CI=1.05-1.60). Our study demonstrates an
      association between whole brain atrophy rate and subsequent rate of clinical
      progression from MCI to AD. These findings suggest that IPCA could be an
      effective brain-imaging marker of progression to AD and useful tool for the
      evaluation of disease-modifying treatments.

PMID- 18829138
TI  - [Sarcopenia].
AB  - Sarcopenia is defined by loss of muscular mass, strength and quality that occurs
      in elderly. It has become an important area of research because of its frequency
      and its responsibility for a significant part of the mobility disability in older
      people. Understanding and treating sarcopenia could probably have a dramatic
      impact on the disability process. A definitive consensual clinical method to
      assess sarcopenia is still needed in everyday clinical practice and clinical
      research. The different characteristics that define sarcopenia are usually
      studied separately. The loss of muscular mass and muscle strength is mainly
      caused by low physical activity, aged-related changes in steroids hormones and
      inflammatory processes. Treatment relies on a multidimensional approach.
      Preventing loss of muscle mass and preserving muscle strength is relevant if it
      prevents decline in physical performance and mobility disability. Identifying
      target elderly populations for specific treatment in clinical trial is an
      important issue. To date strength training is the only efficient approach to
      treat and prevent sarcopenia. So far, no pharmacological treatment has proven
      definitive evidence to treat or prevent sarcopenia. On-going and future
      pharmacological clinical trials may radically change our therapeutic approach of
      mobility disability in elderly. The endpoint prevention of mobility disability
      should be added to the well-established outcomes of treatment of the loss of
      muscular mass, muscle strength or muscle quality.

PMID- 18829137
TI  - Reproductive age modulates the impact of focal ischemia on the forebrain as well
      as the effects of estrogen treatment in female rats.
AB  - While human observational studies and animal studies report a neuroprotective
      role for estrogen therapy in stroke, the multicenter placebo-controlled Women's
      Health Initiative (WHI) study concluded that hormone therapy increased the risk
      for stroke in postmenopausal women. The present study therefore tested the
      hypothesis that estrogen replacement would increase the severity of a stroke-like
      injury in females when this replacement occurs after a prolonged hypoestrogenic
      period, such as the menopause or reproductive senescence, but not when given to
      females that were normally cycling immediately prior to the hormone replacement.
      Two groups of female rats were used: multiparous females with normal but
      lengthened estrus cycles (mature adults), and older multiparous females currently
      in a persistent acyclic state (reproductive senescent). Animals were either used
      intact, or were bilaterally ovariectomized and immediately replaced with a 17beta
      estradiol pellet or control pellet. Animals were subject to a forelimb placing
      test (a test for sensorimotor deficit) and thereafter to middle cerebral artery
      occlusion (MCAo) by stereotaxic injection of the vasoconstrictive peptide
      endothelin-1, adjacent to the MCA. One week after stroke, behavioral tests were
      performed again. Cortical and striatal infarct volume, measured from brain
      slices, was significantly greater in intact reproductive senescent females as
      compared to intact mature adults. Furthermore, estrogen treatment to
      ovariectomized mature adult females significantly reduced the cortical infarct
      volume. Paradoxically, estrogen treatment to ovariectomized reproductive
      senescent females significantly increased cortical and striatal infarct volumes
      as compared to control pellet replaced senescent females. Significant post-stroke
      behavioral deficit was observed in all groups on the side contralateral to the
      lesion, while senescent females also exhibited deficits on the ipsilateral side,
      in the cross-midline forelimb placement test. Using an animal model that
      approximates the natural ovarian aging process, these findings strongly support
      the hypothesis that the effectiveness of estrogen therapy in protecting brain
      health may depend critically on the time of initiation with respect to a female's
      reproductive status.

PMID- 18829139
TI  - [Disseminated arterial occlusions revealing bilateral venous thrombosis with
      paradoxical embolisms].
AB  - Paradoxical embolism is a diagnosis of exclusion. Clinical triad associates deep
      venous thrombosis with or without pulmonary embolism, arterial embolism, and
      intracardiac communication with right-to-left shunt. The intracardiac
      communication is generally related to a patent foramen ovale (PFO). We report a
      75-year-old patient, who presented with bilateral deep venous thrombosis of the
      legs, complicated by massive pulmonary embolism and paradoxical embolisms through
      a PFO. This resulted in cerebral, mesenteric, splenic and bilateral kidney
      infarctions. A promptly initiated anticoagulant treatment allowed a favourable
      outcome.

PMID- 18829140
TI  - [Recurrent falls in a 73-year-old man].

PMID- 18829141
TI  - Evaluation of a web-based graduate continuing nursing education program in Japan:
      A randomized controlled trial.
AB  - Web-based learning provides educational opportunities for students who are
      independent and self-directed. While the complexities of educational outcomes of
      web-based learning have not yet been completely documented, further studies are
      required using rigorous research design techniques to study the outcomes of web
      based learning as compared to traditional face-to-face learning. The purposes of
      this study were to: (1) assess the learner outcomes of web-based learning as
      compared to face-to-face learning group, and (2) explore methods that maximize
      the use of web-based learning for continuing nursing education. A randomized
      controlled trial of web-based learning in comparison to face-to-face lectures for
      registered nurses or midwives was conducted. One hundred and one nurses and
      midwives were eligible to participate and 93 were randomized, 45 for the web
      based learning and 48 for the face-to face group. Thirty-seven (82.2%) completed
      the web-based learning and 33 (68.8%) the face-to-face program. There was no
      difference in the post-test scores between the web-based learning group
      (mean=76.2) and the face-to-face learning group (mean=79.4) (t=0.66, df=68,
      p=0.51). There were three distinct advantages to the web-based group, even though
      both group demonstrated the same learning outcomes. First the dropout rate was
      lower in the web-based program. Second the flexibility of web-based learning was
      reported by several participants. Finally, web-based learning was attractive to
      an affordable for a wide age range of the nurses.

PMID- 18829142
TI  - Drawing on three discursive modes in learning disability nurse education.
AB  - This article presents ideas generated by a qualitative study exploring the
      complexities of the social construction of learning disability/intellectual
      disability. The ideas are based upon a larger doctoral study which investigated
      the social construction of learning disability as seen through the discourses and
      discursive devices used by nurse teachers in classroom teaching in particular
      during story telling activities to students. The investigations centred upon the
      stories and were supported by subsequent interviews with the teachers and
      observations of teaching sessions. The findings highlight three discursive
      devices which I call discursivemodes used in the social construction of learning
      disability/intellectual disability by nurse educators and help to explain the
      personal and professional tensions experienced by nurses faced with the dominant
      discourses of today.

PMID- 18829143
TI  - Nurses are more efficient than doctors in teaching basic life support and
      automated external defibrillator in nurses.
AB  - BACKGROUND: Cardiac arrest (CA) is a leading cause of death worldwide. The
      European Resuscitation Council (ERC) has developed basic life support/automated
      external defibrillation (BLS/AED) courses for uniform training in out-of-hospital
      CA. OBJECTIVE: The present study compares the resuscitation skills of two groups
      of nursing staff, one taught by newly trained ERC nurse-instructors and the other
      by newly trained doctor-instructors. METHOD: Eighteen doctors and 18 nurses were
      asked to teach a total of 108 nurses in a (BLS/AED) course. One month after its
      completion, all 108 nurses were asked to be re-evaluated, with the use of the
      objective structured clinical examination. CONCLUSIONS: No statistical
      significant difference between the two groups was noted in the written test, in
      contrast with data collected from the practice skills check-list. Nurses in group
      A could easily identify the patient in cardiac arrest but had difficulties
      concerning chest compressions and handling the AED. Nurses in group B were more
      focused during the performances, used AED more accurately and continued
      cardiopulmonary resuscitation with no delays. Nurses prove to be more efficient
      in training nurses.

PMID- 18829144
TI  - Management of dystonia of the lateral pterygoid muscle with botulinum toxin A.
AB  - Oromandibular dystonia (OMD) is a rare neurological condition infrequently seen
      by oral and maxillofacial surgeons which may result in inappropriate deviation of
      the mandible, subluxation and intraoral soft tissue trauma. A case is presented
      of a patient suffering from spasmodic torticollis and lateral pterygoid dystonia
      and currently under treatment with botulinum A toxin (Botox) injections. Botox
      has emerged as the most effective form of symptomatic treatment for
      abnormabilities in muscle movement, namely dystonia with oromandibular symptoms.

PMID- 18829145
TI  - Keratotic basal cell carcinoma of the tongue: case report.
AB  - Basal cell carcinoma (BCC) is the most common skin cancer. Its occurrence in the
      oral mucosa is extremely rare. We report the clinical course of BCC arising in
      the inferior surface of the tongue. We performed a super selective intra-arterial
      chemotherapy combined with radiotherapy for this case. Local tumor response
      showed CR, and no recurrence was seen after the treatment.

PMID- 18829146
TI  - Early accounts of Gulf War illness and the construction of narratives in UK
      service personnel.
AB  - "Gulf War Syndrome" has become firmly established in public and political
      discourse, and considerable numbers of veterans of the 1991 Gulf war now see it
      as part of their identity. In this paper we draw on open-ended questionnaire data
      drawn from a large, random sample of UK Gulf veterans, collected in 1996 and
      1997. Whilst there is already some literature focussing on coherent personal
      narratives of some veterans and campaigners, we suggest that they are preceded by
      much more fragmentary, shared accounts. We take the idea of rumour as a way of
      encapsulating how these partial ideas swiftly gained value by reflecting and
      reproducing social ties. Accounts describing fears about this mystery condition
      simultaneously made reference to concerns about their role as a soldier, about
      the purpose of the conflict, and rising mistrust of their commanders. As doubt
      over soldiers' function increased, informal social networks became increasingly
      significant, perhaps also linked to an erosion of respect for formal military
      hierarchy. At the same time, rumours of "Gulf War Syndrome" began to circulate,
      reinforcing the idea that the cause was elusive, and invisible, whilst
      undermining both the unity of the military force and the individual soldier's
      body. We suggest that the nature of Gulf War Syndrome as a topic of contestation
      in the years after the conflict was keenly shaped by these early rumours, which
      entangled specific ideas of the illness with feelings of betrayal, distrust and
      ambiguity. Informed by the general literature on illness narratives, we explore
      how the transmission of ideas and causal theories were themselves instrumental in
      the emergence of the condition as it was experienced.

PMID- 18829147
TI  - Health promotion research and practice require sound policy analysis models: the
      case of Quebec's Tobacco Act.
AB  - In this paper we illustrate how policy analysis models can deepen our
      understanding of the challenges facing health promoters advocating for policy
      change. Specifically we describe the factors underpinning the adoption of
      Quebec's Tobacco Act (1998) and the role played by actors from governmental
      public health agencies (GPHAs). Data were collected through interviews (n=39),
      newspapers articles (n=569) and documents (n > 200) from GPHAs, NGOs, the Quebec
      National Assembly, and opponents to the legislative measures. Data collection and
      analysis were based on Sabatier and Jenkins-Smith's Advocacy Coalition Framework
      (1999) and Lemieux's theorization of coalition structuring (1998). We explain the
      adoption of the Act by: (1) the broad recognition within the policy elite of the
      main parameters of tobacco use (i.e. lethality, addictive properties, and
      legitimacy of governmental intervention), (2) the impacts of a series of events
      (e.g. cigarette contraband crisis) that enabled tobacco control advocates to
      influence public debates, and the governmental agenda, (3) the critical
      contribution of a coalition of GPHAs pooling resources to address both the
      sanitary and economic aspects of the legislation while countering the
      opposition's strategy, and (4) the failure of the opponents to present an unified
      voice on the definition of the tobacco policy. This study illustrates the merits
      of applying a policy-change model to grasp the complexity of the process. Our
      findings call for the development of permanent policy analysis capabilities
      within public health agencies and for a broader scrutiny of the non-health
      related dimensions of policy debates.

PMID- 18829148
TI  - Effect of Galla chinensis extract and chemical fractions on demineralization of
      bovine enamel in vitro.
AB  - OBJECTIVE: To evaluate the demineralization inhibition property of extracts and
      chemical fractions of Galla chinensis in vitro. METHODS: Seventy sound bovine
      enamels blocks were prepared and randomly divided into seven groups. These
      samples were pH-cycled for 12 times in 6 days. Each daily cycle included 2x 5 min
      application with one of the seven treatments: 1000 ppmFaq. (as NaF, positive
      control); deionized water (negative control); or 4000 ppm aqueous solutions of
      five G. chinensis extracts (GCEs): GCE, GCE-A, GCE-B, GCE-C or GCE-D. Surface
      enamel microhardness was measured on the enamel blocks before and after pH
      cycling, and the reduction of surface microhardness (DeltaSMH) was calculated.
      The acidic buffers were retained for calcium analysis. RESULTS: There were
      significant differences between the GCE groups and the two controls (p<0.01).
      Among all the GCE groups, the reduction of surface microhardness (DeltaSMH) in
      GCE group was the least (p<0.01). No significant differences were found between
      the GCE group and GCE-C group in CDR, as well as the other three GCE groups (GCE
      A, GCE-B and GCE-D) (p>0.05). CONCLUSIONS: The present study has demonstrated the
      potential of the GCE to effect the demineralization under dynamic pH-cycling
      conditions. None of the chemical fractions was as effective as GCE. Combined with
      its anti-bacterial properties, the demineralization inhibition of GCE suggests
      that this material could be a useful source for the development of promising anti
      cariogenic agents.

PMID- 18829149
TI  - Comment on: Construction of simplified models to simulate estrogenic disruptions
      by esters of 4-hydroxybenzoic acid (parabens). Patricia Guadarrama, Serguei
      Fomine, Roberto Salcedo, Ana Martinez. Biophys. Chem. 137 (2008) 1-6.
      doi:10.1016/j.bpc2008.06.001.

PMID- 18829150
TI  - A real-time freehand ultrasound calibration system with automatic accuracy
      feedback and control.
AB  - This article describes a fully automatic, real-time, freehand ultrasound
      calibration system. The system was designed to be simple and sterilizable,
      intended for operating-room usage. The calibration system employed an automatic
      error-retrieval and accuracy-control mechanism based on a set of ground-truth
      data. Extensive validations were conducted on a data set of 10,000 images in 50
      independent calibration trials to thoroughly investigate the accuracy,
      robustness, and performance of the calibration system. On average, the
      calibration accuracy (measured in three-dimensional reconstruction error against
      a known ground truth) of all 50 trials was 0.66 mm. In addition, the calibration
      errors converged to submillimeter in 98% of all trials within 12.5 s on average.
      Overall, the calibration system was able to consistently, efficiently and
      robustly achieve high calibration accuracy with real-time performance.

PMID- 18829151
TI  - A double-blind trial of clinical effects of therapeutic ultrasound in knee
      osteoarthritis.
AB  - A randomized double blind clinical trial was conducted to determine the
      effectiveness of ultrasound (US) therapy in knee osteoarthritis (OA). Sixty-seven
      patients (mean age 54.8 +/-7) were randomized to receive either 1 MHz frequency
      or 1 watt/cm(2) power continuous ultrasound for 5 min (n = 34) or sham US (n =
      33) as a placebo. Ten sessions of treatment were applied to the target knee of
      the patient. A blinded evaluation at baseline and after treatment was made.
      Primary outcome was pain on movement assessed by visual analog scale (VAS).
      Secondary outcomes consisted of the Western Ontario and McMaster Universities
      Osteoarthritis Index (WOMAC) scores and 50 meters walking time. Both groups
      showed significant improvements in knee pain on movement. In the treatment group,
      the improvement in VAS score was statistically and significantly higher (p <
      0.001) and more pronounced than in the placebo group. Pain reduction averaged
      47.76% in the treatment group (p = 0.013). Secondary outcomes improved in both
      groups but reached statistical significance only in the treatment group: p =
      0.006 for the mean change in total WOMAC scores and p = 0.041 for 50 meters
      walking time. Results suggest that therapeutic US is safe and effective treatment
      modality in pain relief and improvement of functions in patients with knee OA.

PMID- 18829152
TI  - Identification of a cis-acting element responsive to ultrasound in the 5'
      flanking region of the human heme oxygenase-1 gene.
AB  - We previously found that the heme oxygenase-1 gene (hmox-1) was the most
      upregulated gene among 9,182 genes in human lymphoma U937 cells exposed to a 1
      MHz continuous ultrasound using the cDNA microarray technique. However, little is
      known about the molecular mechanisms of the induction of hmox-1 expression by
      ultrasound. We investigated the mechanism using human prostate cancer DU145 cells
      in which expression of hmox-1 increased with sonication in a time and an
      intensity-dependent manner. When N-acetyl-L-cysteine or glutathione-monoethyl
      ester, a potent antioxidant, was added to cell culture, hmox-1 upregulation was
      attenuated, suggesting that oxidative stress caused by sonication is involved in
      this process. To identify cis-acting elements required for the ultrasound
      mediated induction, we carried out transient expression assays with plasmids
      carrying the luciferase gene under control of deletion mutants of the 5'-flanking
      region of hmox-1. The results revealed that the upregulations by sonication were
      observed with deletion mutants carrying the E1 or E2 enhancer of the 5'-flanking
      region, suggesting stress-responsive elements (StRE) were involved in the
      induction because either enhancer contains a number of the element. Indeed, site
      directed mutations within StRE decreased the reactivity of deletion mutants to
      sonication. A transcription factor NF-E2-related Factor 2 that binds to StRE
      would therefore be activated by oxidative stress induced by sonication.

PMID- 18829153
TI  - Pressure-dependent attenuation and scattering of phospholipid-coated microbubbles
      at low acoustic pressures.
AB  - Previous optical studies have shown threshold behavior of single-contrast agent
      microbubbles. Below the acoustic pressure threshold, phospholipid-coated
      microbubbles with sizes <5.0 mum in diameter oscillate significantly less than
      above the threshold pressure. Previous studies also revealed an acoustic pressure
      dependent attenuation of ultrasound by microbubble contrast agents. In this
      study, we investigated whether pressure-dependent acoustic behavior may be
      explained by threshold behavior. For this purpose, pressure-dependent attenuation
      and scattering of a phospholipid-coated contrast agent were measured. Transmit
      frequencies between 1.5 and 6.0 MHz and acoustic pressures between 5 and 200 kPa
      were applied. Unlike the galactose-based contrast agent Levovist, the
      phospholipid-coated contrast agent BR14 showed a pressure-dependent attenuation.
      In addition, it was found that filtered suspensions with only microbubbles <3.0
      mum in diameter show more pressure-dependent attenuation behavior than native
      suspensions of phospholipid-coated microbubbles. For the scattering measurements
      conducted at 3.0 MHz, the native suspension did not show any pressure-dependent
      behavior. However, the filtered suspension responded highly nonlinearly. Between
      30 and 150 kPa, 16 dB additional scattered power was obtained. We concluded that
      threshold behavior of phospholipid-coated microbubbles results in pressure
      dependent attenuation and scattering.

PMID- 18829154
TI  - Re: Christopher R. Chapple, Vik Khullar, Zahava Gabriel, et al. The effects of
      antimuscarinic treatments in overactive bladder: an update of a systematic review
      and meta-analysis. Eur Urol 2008;54:543-62.

PMID- 18829155
TI  - Inhibition of MEK blocks GRP78 up-regulation and enhances apoptosis induced by ER
      stress in gastric cancer cells.
AB  - We studied potential interactions between the endoplasmic reticulum (ER) stress
      response and the MEK/ERK pathway. Induction of ER stress did not trigger
      significant apoptosis, but caused rapid activation of ERK1/2 in gastric cancer
      cells. Inhibition of MEK enhanced ER stress-induced apoptosis via a caspase
      dependent, mitochondria-mediated mechanism. This was associated with blockage of
      ER stress-mediated up-regulation of GRP78. The latter appeared to be critical in
      antagonizing the apoptosis-inducing potential of ER stress. Thus, activation of
      MEK/ERK by ER stress is necessary for induction of GRP78 that protects against
      apoptosis in gastric cancer cells submitted to ER stress.

PMID- 18829156
TI  - Optimising ultrasound-mediated gene transfer (sonoporation) in vitro and
      prolonged expression of a transgene in vivo: potential applications for gene
      therapy of cancer.
AB  - Therapeutic approaches using gene-based medicines promise alternatives or
      adjuncts to conventional cancer treatment. Because of its non-invasive nature,
      ultrasound, as a membrane-permeabilising stimulus has the potential to be highly
      competitive with viral gene delivery and existing non-viral alternatives. In
      optimising ultrasound-mediated, microbubble-assisted (MB101) gene tranfection in
      vitro, we demonstrate efficiencies of up to 18% using ultrasound at 1 MHz at a
      duty cycle of 25% at intensities ranging from 1 to 4 W cm(-2). Using ultrasound
      mediated transfection together with an episomal plasmid-based gene expression
      system, we demonstrate prolonged functional gene expression of luciferase in
      mouse hind leg muscle and in tumours in vivo.

PMID- 18829157
TI  - Lycorine induces apoptosis and down-regulation of Mcl-1 in human leukemia cells.
AB  - Lycorine is an alkaloid isolated from the bulb of the Amaryllidaceae Lycoris.
      Here, we report that treatment with lycorine resulted in survival inhibition and
      apoptosis induction in human leukemia cell lines. Lycorine induced apoptosis in
      human leukemia cells via intrinsic mitochondria pathway and caused a rapid
      turnover of protein level of Mcl-1 which occurred before caspases activation.
      Furthermore, pronounced apoptosis accompanied by the down-regulation of Mcl-1 was
      also observed in blasts from patients with acute myeloid leukemia. Our findings
      suggest that lycorine may be a good candidate therapeutic agent against leukemia
      in worth of further evaluation.

PMID- 18829158
TI  - Effect of filler types and calcination temperature on the microstructure and the
      nitric oxide photocatalytic activity of composite titanium dioxide films.
AB  - The composite titanium dioxide (TiO(2)) films coating on the woven glass fabric
      were prepared by a modified sol-gel process, using pre-calcinated TiO(2)
      nanoparticle or silica gel as filler. The characterized physicochemical
      properties of the prepared catalyst films showed that the specific surface area,
      the microstructure and the crystal structure of the catalysts were greatly
      affected by the fillers and the calcination temperature. The physicochemical
      properties of composite films and the photocatalytic activity of nitric oxide
      (NO) show that the pre-calcinated TiO(2) nanoparticle is more favorable than
      silica gel as filler. The pre-calcinated TiO(2) nanoparticle filler can increase
      the photocatalytic activities of the catalysts by increasing the specific surface
      area, introducing a bimodal mesoporous structure, and creating a polymorphous
      crystal structure. And the TiO(2)-TiO(2) film calcinated at 400 degrees C
      exhibits the highest photocatalytic activity for NO oxidation and is more active
      than Degussa P25.

PMID- 18829159
TI  - Quaternary herbicides retention by the amendment of acid soils with a bentonite
      based waste from wineries.
AB  - The agronomic utility of a solid waste, waste bentonite (WB), from wine companies
      was assessed. In this sense, the natural characteristics of the waste were
      measured, followed by the monitoring of its effects on the adsorption/desorption
      behaviour of three quaternary herbicides in acid soils after the addition of
      increasing levels of waste. This was done with the intention of studying the
      effect of the added organic matter on their adsorption. The high content in C
      (294 g kg(-1)), N (28 g kg(-1)), P (584 mg kg(-1)) and K (108 g kg(-1)) of WB
      turned it into an appropriate amendment to increase soil fertility, solving at
      the same time its disposal. WB also reduced the potential Cu phytotoxicity due to
      a change in Cu distribution towards less soluble fractions. The adsorption of the
      herbicides paraquat, diquat and difenzoquat by acid soils amended with different
      ratios of WB was measured. In all cases, Langmuir equation was fitted to the
      data. Paraquat (PQ) and diquat (DQ) were adsorbed and retained more strongly than
      difenzoquat (DFQ) in the acid soil studied. However, the lowest retention of DFQ
      in an acid soil can be increased by amendment with organic matter through a solid
      waste from wineries, and it is enough for duplicate retention a dosage rate of
      10t/ha. Anyway, detritivores ecology can still be affected. Detritivores are the
      organisms that consume organic material, and in doing so contribute to
      decomposition and the recycling of nutrients. The term can also be applied to
      certain bottom-feeders in wet environments, which play a crucial role in benthic
      ecosystems, forming essential food chains and participating in the nitrogen
      cycle.

PMID- 18829160
TI  - Estimation of chromium(VI) sorption efficiency of novel regenerable p-tert
      butylcalix[8]areneoctamide impregnated Amberlite resin.
AB  - The article describes a convenient synthesis and Cr(VI) extraction efficiency of
      a novel p-tert-butylcalix[8]areneoctamide impregnated Amberlite (XAD-4) resin.
      Using p-tert-butylcalix[8]arene macrocyclic building block, two strategies have
      been developed; i.e., derivatization of p-tert-butylcalix[8]arene framework with
      sophisticated ionophoric groups having efficiency to extract oxoanions from
      aqueous media and, impregnation of p-tert-butylcalix[8]arene derivative onto the
      polymeric support. Liquid-liquid and solid-liquid extraction experiments have
      been performed to evaluate the Cr(VI) extraction efficiency of both p-tert
      butylcalix[8]arene derivative and the impregnated resin. From the results, it has
      been deduced that solid-phase extraction method is more convenient and efficient
      than liquid-liquid extraction process. The impregnated XAD-4 resin has been found
      regenerable with better extracting efficiency as compared to the simple p-tert
      butylcalix[8]areneoctamide ionophore.

PMID- 18829161
TI  - Human dietary exposure to polychlorinated dibenzo-p-dioxins and polychlorinated
      dibenzofurans in Taiwan.
AB  - Polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans
      (PCDFs) levels in a total of 25 food items in Taiwan were surveyed. It was
      observed that shellfish and saltwater fish possessed the highest PCDD/Fs levels,
      9.82 and 3.60 pg WHO-TEQ/g, respectively, on the lipid basis. The dietary intakes
      of humans at the ages of 12-18, 19-64, and over 65 were determined. The estimated
      intake were between 21.8 pg (female teenagers) and 37.6 pg (male seniors) WHO
      TEQ/day; the levels varied with the dietary habits. The PCDD/F intakes for all
      human groups are far below the tolerable limit of 70 pg WHO-TEQ/kg b.w./month. In
      addition, the daily PCDD/F intake levels for duck-farmers consuming average and
      large amounts of PCDD/F contaminated duck eggs were examined. The result shows
      that consuming more than one duck egg with level higher than 10 pg WHO-TEQ/g
      lipid of PCDD/Fs per day could lead to a PCDD/F intake level higher than the
      tolerable limit. However, for normal population, there is a little risk to ingest
      intolerable amount of PCDD/Fs because of consuming contaminated duck eggs.

PMID- 18829162
TI  - Recycling of waste printed circuit boards: a review of current technologies and
      treatment status in China.
AB  - From the use of renewable resources and environmental protection viewpoints,
      recycling of waste printed circuit boards (PCBs) receives wide concerns as the
      amounts of scrap PCBs increases dramatically. However, treatment for waste PCBs
      is a challenge due to the fact that PCBs are diverse and complex in terms of
      materials and components makeup as well as the original equipment's manufacturing
      processes. Recycle technology for waste PCBs in China is still immature. Previous
      studies focused on metals recovery, but resource utilization for nonmetals and
      further separation of the mixed metals are relatively fewer. Therefore, it is
      urgent to develop a proper recycle technology for waste PCBs. In this paper,
      current status of waste PCBs treatment in China was introduced, and several
      recycle technologies were analyzed. Some advices against the existing problems
      during recycling process were presented. Based on circular economy concept in
      China and complete recycling and resource utilization for all materials, a new
      environmental-friendly integrated recycling process with no pollution and high
      efficiency for waste PCBs was provided and discussed in detail.

PMID- 18829163
TI  - Development and application of a novel swirl cyclone scrubber (2) Theoretical.
AB  - The swirl cyclone scrubber analyzed in this paper is a novel aerosol filtering
      device in which a uniflow cyclone and a scrubber are combined. Systematic
      experiments showed that the swirl scrubber is a promising device that has minimal
      installation, operational, and maintenance costs. In this article, theoretical
      analyses are developed for the swirl cyclone scrubber. The dependency of particle
      collection efficiency on the design and operating parameters observed by
      experiments is explained using a theoretical parameterization to provide
      guidelines for optimal design and operation of the device. Discussion on possible
      variations of the swirl cyclone scrubber is also presented based on the
      theoretical parameterization developed.

PMID- 18829164
TI  - Management of antibiotic residues from agricultural sources: use of composting to
      reduce chlortetracycline residues in beef manure from treated animals.
AB  - Chlortetracycline (CTC) is one of only ten antibiotics licensed in the U.S.A. for
      use as growth promoters for livestock. The widespread use and persistence of CTC
      may contribute in development of antibiotic-resistant bacteria. The objective of
      this study was to determine the effect of composting on the fate of CTC residues
      found in manure from medicated animals. The effect of CTC residues on composting
      was also investigated. Five beef calves were medicated for 5 days with 22
      mg/kg/day of CTC. Manure samples collected from calves prior to and after
      medication were mixed with straw and woodchips, and aliquots of the subsequent
      mixtures were treated in laboratory composters for 30 days. In addition, aliquots
      of the CTC-containing mixture were incubated at 25 degrees C or sterilized
      followed by incubation at 25 degrees C and 55 degrees C (composting temperature).
      The presence of CTC did not appear to affect the composting process.
      Concentrations of CTC/ECTC (the summed concentrations of CTC and its epimer ECTC)
      in the composted mixture (CM) and sterilized mixture incubated at 55 degrees C
      (SM55) decreased 99% and 98% (from 113 microg/g dry weight (DW) to 0.7 microg/g
      DW and 2.0 microg/g DW), respectively, in 30 days. In contrast, levels of
      CTC/ECTC in room temperature incubated (RTIM) and sterilized mixture incubated at
      25 degrees C (SM25) decreased 49% and 40% (to 58 microg/g DW and 68 microg/g DW),
      respectively, after 30 days. Concentrations of the CTC metabolite, iso
      chlortetracycline (ICTC), in CM and SM55 decreased more than 99% (from 12
      microg/g DW to below quantitation limit of 0.3 microg/g DW) in 30 days. ICTC
      levels in RTIM and SM25 decreased 80% (to 4 microg/g DW) in 30 days. These
      results confirm and extend those from previous studies that show the increased
      loss of extractable CTC residues with increased time and incubation temperature.
      In addition, our results using sterile and non-sterile samples suggest that the
      decrease in concentrations of extractable CTC/ECTC at 25 degrees C and 55 degrees
      C (composting temperature) is due to abiotic processes.

PMID- 18829165
TI  - Evaluation of persulfate oxidative wet scrubber for removing BTEX gases.
AB  - Soil vapor extraction (SVE) coupled with air sparging of groundwater is a method
      commonly used to remediate soil and groundwater contaminated with volatile
      organic petroleum contaminants such as gasoline. These hazardous contaminants are
      mainly attributable to the compounds-benzene, toluene, ethylbenzene, and xylenes
      (known collectively as BTEX). Exhaust gas from SVE may contain BTEX, and
      therefore must be treated before being discharged. This study evaluated the use
      of iron-activated persulfate chemical oxidation in conjunction with a wet
      scrubbing system, i.e., a persulfate oxidative scrubber (POS) system, to destroy
      BTEX gases. The persulfate anions can be activated by citric acid (CA) chelated
      Fe(2+) to generate sulfate radicals (SO(4)(*-), E degrees =2.4V), which may
      rapidly degrade BTEX in the aqueous phase and result in continuous destruction of
      the BTEX gases. The results show that persulfate activation occurred as a result
      of continuous addition of the citric acid chelated Fe(2+) activator, which
      readily oxidized the dissolved BTEX. Based on initial results from the aqueous
      phase, a suitable Fe(2+)/CA molar ratio of 5/3 was determined and used to
      initiate activation in the subsequent POS system tests. In the POS system, using
      persulfate as a scrubber solution and with activation by injecting Fe(2+)/CA
      activators under two testing conditions, varying iron concentrations and pumping
      rates, resulted in an approximate 50% removal of BTEX gases. During the course of
      the tests which in corporate activation, a complete destruction of BTEX was
      achieved in the aqueous phase. It is noted that no removal of BTEX occurred in
      the control tests which did not include activation. The results of this study
      would serve as a reference for future studies into the practical chemical
      oxidation of waste gas streams.

PMID- 18829166
TI  - Ex-situ bioremediation of polycyclic aromatic hydrocarbons in sewage sludge.
AB  - Polycyclic aromatic hydrocarbons (PAH) are regarded as environmental pollutants.
      A promising approach to reduce PAH pollution is based on the implementation of
      the natural potential of some microorganisms to utilize hydrocarbons. In this
      study Proteiniphilum acetatigenes was used for bioaugmentation of sewage sludge
      to improve the PAH removal. Bioaugmentation experiments were performed in
      parallel semi-continuously fed reactors started up with digested primary and
      secondary sludge. Three bioaugmentation approaches were investigated: A1,
      addition of bacteria once during starting up; A2, addition of bacteria at the
      beginning and then every 2nd day and A3, addition of encapsulated bacteria once
      during starting up. Removal of PAH was found to be both biotic and abiotic. All
      three approaches had a positive effect of the biological removal of PAH. Highest
      biological removal of individual PAH (up to 80%) was observed using continuous
      addition (approach A2) of the bacteria to the reactors. In general, the effect of
      bioaugmentation was higher in the reactors fed with primary sludge compared to
      the reactors fed with mixed sludge. Bioaugmentation resulted in biological
      removal of low molecular weight PAH in the reactors fed with primary sludge using
      all three approaches while clear biological removal of the medium- and high
      molecular weight PAH only was observed if the bacteria were added continuously
      (approach A2).

PMID- 18829167
TI  - Extensive radioactive characterization of a phosphogypsum stack in SW Spain:
      226Ra, 238U, 210Po concentrations and 222Rn exhalation rate.
AB  - Phosphogypsum (PG) is a by-product of the phosphate fertilizer industries that
      contains relatively high concentrations of uranium series radionuclides. The US
      EPA regulates the agriculture use of PG, attending to its (226)Ra content and to
      the (222)Rn exhalation rate from inactive stacks. Measurements of (222)Rn
      exhalation rates in PG stacks typically show a large and still poorly understood
      spatial and temporal variability, and the published data are scarce. This work
      studies an inactive PG stack in SW Spain of about 0.5 km(2) from where PG can be
      extracted for agriculture uses, and an agriculture soil 75 km apart, being
      representative of the farms to be amended with PG. Activity concentrations of
      (226)Ra, (238)U and (210)Po have been measured in 30 PG samples (0-90 cm horizon)
      allowing for the construction of maps with spatial distributions in the PG stack
      and for the characterization of the associated PG inputs to agriculture soils.
      Averaged (226)Ra concentrations for the stack were 730+/-60 Bq kg(-1) (d.w.),
      over the US-EPA limit of 370 Bq kg(-1). (222)Rn exhalation rate has been measured
      by the charcoal canister method in 49 sampling points with 3 canisters per
      sampling point. Values in PG stack were under the US-EPA limit of 2600 Bq m(-2)h(
      1), but they were one order of magnitude higher than those found in the
      agriculture soil. Variability in radon emissions has been studied at different
      spatial scales. Radon exhalation rates were correlated with (226)Ra
      concentrations and daily potential evapotranspiration (ETo). They increased with
      ETo in agriculture soils, but showed an opposite behaviour in the PG stack.

PMID- 18829168
TI  - Application of multicriteria decision analysis to jar-test results for chemicals
      selection in the physical-chemical treatment of textile wastewater.
AB  - Jar-test is a well-known tool for chemicals selection for physical-chemical
      wastewater treatment. Jar-test results show the treatment efficiency in terms of
      suspended matter and organic matter removal. However, in spite of having all
      these results, coagulant selection is not an easy task because one coagulant can
      remove efficiently the suspended solids but at the same time increase the
      conductivity or increase considerably the sludge production containing chemicals
      and toxic dyes. This makes the final selection of coagulants very dependent on
      the relative importance assigned to each measured parameter. In this paper, the
      use of multicriteria decision analysis (MCDA) is proposed to help on the
      selection of the coagulant and its concentration in the physical-chemical
      wastewater treatment, since textile wastewater contains hazardous substances.
      Therefore, starting from the parameters fixed by the jar-test results, these
      techniques will allow to weight these parameters, according to the judgements of
      wastewater experts, and to establish priorities among coagulants. Two well-known
      MCDA techniques have been used: analytic hierarchic process (AHP) and preference
      ranking organization method for enrichment evaluations (PROMETHEEs) and their
      results were compared. The method proposed has been applied to the particular
      case of textile wastewaters. The results obtained show that MCDA techniques are
      useful tools to select the chemicals for the physical-technical treatment.

PMID- 18829169
TI  - Simulated solar UV-irradiation of endocrine disrupting chemical octylphenol.
AB  - The photolysis of octylphenol (OP) was investigated using a solar simulator in
      the absence/presence of dissolved natural organic matter (DNOM), HCO(3)(-),
      NO(3)(-) and Fe(III) ions. The effects of different parameters such as initial
      pH, initial concentration of substrate, temperature, and the effect of hydrogen
      peroxide concentration on photodegradation of octylphenol in aqueous solution
      have been assessed. The results indicate that the oxidation rate increases in the
      presence of H(2)O(2), nitrate and DNOM. Phenol, 1,4-dihydroxylbenzene and 1,4
      benzoquinone were identified as intermediate products of photodegradation of
      octylphenol, through an HPLC method. In addition, the disappearance of the
      estrogenic activity of octylphenol during irradiation using YES test was
      investigated. Based upon the YES test results, there was a strong decrease of
      estrogenic activity of octylphenol after 8h irradiation in the presence of
      hydrogen peroxide.

PMID- 18829170
TI  - Biodegradation of phenol by Pseudomonas putida immobilized in polyvinyl alcohol
      (PVA) gel.
AB  - Batch experiments were carried out to evaluate the biodegradation of phenol by
      Pseudomonas putida immobilized in polyvinyl alcohol (PVA) gel pellets in a bubble
      column bioreactor at different conditions. The bacteria were activated and
      gradually acclimatized to high concentrations of phenol of up to 300 mg/l. The
      experimental results indicated that the biodegradation capabilities of P. putida
      are highly affected by temperature, pH, initial phenol concentration and the
      abundance of the biomass. The biodegradation rate is optimized at 30 degrees C, a
      pH of 7 and phenol concentration of 75 mg/l. Higher phenol concentrations
      inhibited the biomass and reduced the biodegradation rate. At high phenol
      concentration, the PVA particle size was found to have negligible effect on the
      biodegradation rate. However, for low concentrations, the biodegradation rate
      increased slightly with decreasing particle size. Other contaminants such heavy
      metals and sulfates showed no effect on the biodegradation process. Modeling of
      the biodegradation of phenol indicated that the Haldane inhibitory model gave
      better fit of the experimental data than the Monod model, which ignores the
      inhibitory effects of phenol.

PMID- 18829171
TI  - SnSAG5 is an alternative surface antigen of Sarcocystis neurona strains that is
      mutually exclusive to SnSAG1.
AB  - Sarcocystis neurona is an obligate intracellular parasite that causes equine
      protozoal myeloencephalitis (EPM). Previous work has identified a gene family of
      paralogous surface antigens in S. neurona called SnSAGs. These surface proteins
      are immunogenic in their host animals, and are therefore candidate molecules for
      development of diagnostics and vaccines. However, SnSAG diversity exists in
      strains of S. neurona, including the absence of the major surface antigen gene
      SnSAG1. Instead, sequence for an alternative SnSAG has been revealed in two of
      the SnSAG1-deficient strains. Herein, we present data characterizing this new
      surface protein, which we have designated SnSAG5. The results indicated that the
      protein encoded by the SnSAG5 sequence is indeed a surface-associated molecule
      that has characteristics consistent with the other SAGs identified in S. neurona
      and related parasites. Importantly, Western blot analyses of a collection of S.
      neurona strains demonstrated that 6 of 13 parasite isolates express SnSAG5 as a
      dominant surface protein instead of SnSAG1. Conversely, SnSAG5 was not detected
      in SnSAG1-positive strains. One strain, which was isolated from the brain of a
      sea otter, did not express either SnSAG1 or SnSAG5. Genetic analysis with SnSAG5
      specific primers confirmed the presence of the SnSAG5 gene in Western blot
      positive strains, while also suggesting the presence of a novel SnSAG sequence in
      the SnSAG1-deficient, SnSAG5-deficient otter isolate. The findings provide
      further indication of S. neurona strain diversity, which has implications for
      diagnostic testing and development of vaccines against EPM as well as the
      population biology of Sarcocystis cycling in the opossum definitive host.

PMID- 18829172
TI  - HPA-axis regulation at in-patient admission is associated with antidepressant
      therapy outcome in male but not in female depressed patients.
AB  - A concatenation of data implicates a hyperactivity of the hypothalamus pituitary
      adrenal (HPA)-axis in the pathogenesis of depression and its normalization as a
      necessary predecessor of clinical response to antidepressant drugs. In addition,
      regulation of the HPA-axis has been shown to be dependent on sex hormones. We
      therefore investigated gender differences in HPA-axis regulation in depression
      and its normalization during remission of clinical symptoms. We used the combined
      dexamethasone suppression/CRH stimulation (Dex-CRH) test to evaluate the degree
      of HPA-axis dysregulation in 194 in-patients with unipolar depression from the
      Munich Antidepressant Response Signature (MARS) study at both admission and
      discharge. The Hamilton Depression (HAM-D) Rating Scale was used to monitor
      clinical response to antidepressant treatment. For both genders, we observed a
      normalization of HPA-axis dysregulation in remitters but not in non-remitters,
      both after 5 weeks of treatment and at discharge. The pattern of HPA-axis
      normalization with remission of depressive symptoms, however, showed gender
      specific differences. In male patients, remission after 5 weeks of in-patient
      treatment was associated with a significantly higher cortisol response in the Dex
      CRH test at admission. In female patients, 5-week remitters and non-remitters had
      a comparable cortisol response at admission. Cortisol response at admission was
      not correlated with gonadal steroid levels at this time point and the results
      were similar for pre-menopausal women vs. post-menopausal women. Gender
      associated biological characteristics, likely independent of circulating gonadal
      steroids, thus seem to influence HPA-axis regulation in depression. In male
      patients, a single measure of HPA-axis dysregulation at admission may serve as a
      predictor of response to antidepressant treatment in addition to the previously
      reported repeated measure of the Dex-CRH test.

PMID- 18829173
TI  - The sunspot theory of schizophrenia: further evidence, a change of mechanism, and
      a strategy for the elimination of the disorder.
AB  - The Gestational Zinc Deficiency Theory suggests that the schizophrenia is caused
      by a spectrum of damage, produced in utero, to zinc dependent fetal organs such
      as the brain, pancreas, pineal, testes etc. One problem encountered by the theory
      is how such deficiency could occur given that the disorder is fairly uniformly
      distributed across the planet. The original explanation, that seasonal variation
      in zinc availability was responsible is unconvincing and a search for clues led
      to an investigation of the Recency Theory which argues that schizophrenia was
      unknown before 1750 and that an "epidemic of insanity" began around 1780 and
      stabilized around 1900. The Sunspot Theory arose from the realization that
      Juckett and Rosenberg's finding of a strong correlation between solar activity
      and longevity might, with some modification, explain both changes in the
      incidence of the disorder and the origin of the maternal zinc deficiency. The
      twenty year shift required to give optimal correlation was explained by these
      authors as being caused by ionizing radiation induced changes to developing fetal
      germinal cells. In the sunspot theory it was suggested that the correlation
      between solar activity and schizophrenia incidence was due to changes in maternal
      zinc metabolism following microwave induced stress. In this article it will be
      shown that that mechanism was incorrect. A far better explanation is provided by
      assuming that geomagnetic field induced loss of pineal activity in the mother
      during pregnancy permanently affects pineal entrainment in the fetus. In addition
      it is shown that the loss of correlation between solar activity and longevity
      during the 1800 to 1830 period identified by Juckett and Rosenberg explains a
      hitherto inexplicable decline, between 1877 and 1887, in the rising graph of
      schizophrenia incidence. Finally, the hypothesis, if correct suggests that a
      strategy based on zinc and melatonin supplements given to at risk parents may go
      some way to eliminating the disorder.

PMID- 18829174
TI  - Is exercise beneficial to the inflammatory bowel diseases? An implication of heat
      shock proteins.
AB  - Inflammatory bowel diseases (IBD) cause the intestines to become inflamed (red
      and swollen) and typically include Crohn's disease and ulcerative colitis. Heat
      shock protein (Hsp)70, which exhibits greater expression in the intestines of
      patients with IBD, may act to protect the intestine against this inflammatory
      insult. However, most procedures for eliciting this protective response, such as
      heating and/or pharmacological interventions are non-physiological and can have
      serious side-effects. Exercise is a biologically relevant means of inducing
      protective heat shock proteins in the myocardium and other organs but it has yet
      to be studied in the bowel. We herein hypothesize that (1) exercise will be
      beneficial in reducing the occurrence of IBD and suppressing intestine
      inflammatory injuries, (2) exercise will provide protection through induction of
      anti-inflammatory Hsps. Further studies using both genetically manipulated animal
      models and animals undergoing exercise are needed to determine the efficacy of
      exercise and the role of Hsps in inhibiting or treating inflammatory bowel
      disease.

PMID- 18829175
TI  - A new probe for targeting drug delivery system.
AB  - Recently, TDDS (Targeting drug delivery system) plays an important role in
      enhancing the bioavailability and targeting of anti-tumor drugs. How to transport
      drugs quickly and precisely to their target sites of action has not been solved
      fundamentally. A large number of researches have identified artemisinin and its
      analogs have the merit of precisely targeting to cancer cell, and low side
      effects to healthy tissue. Thus, if these compounds could be attached to
      established anti-tumor drugs with probe, a novel targeting anti-tumor drugs will
      be put into practice in the future. The novel drugs delivery system will be a
      powerful weapon against cancer disease for their unique targeting.

PMID- 18829176
TI  - P450 CYP1B1 mediated fluorescent tumor markers: a potentially useful approach for
      photodynamic therapy, diagnosis and establishing surgical margins.
AB  - Fluorescent tumor markers and other chemicals that concentrate in tumors and can
      be utilized in photodynamic therapy to yield cytotoxins in the form of reactive
      oxygen species have been of interest for a number of years. In addition, the use
      of fluorescent markers for the purpose of tumor tissue visualization continues to
      be of considerable interest. One of the challenges has been to achieve a high
      concentration of the marker or chemical in tumor tissues, ideally approaching
      100% specificity, a goal that appears rarely realized. Furthermore, a high degree
      of localization would limit systemic side effects from general light exposure
      which is a problem with some photodynamic agents. It is suggested that the
      cytochrome P450 enzyme CYP1B1 may offer a novel solution to this problem, since
      it is overexpressed in tumor tissues independent of oncogenic origin, almost
      entirely absent in normal tissues, and through the metabolism of selected
      substrates may be able to generate compounds of interest in photodynamic therapy,
      and in addition fluorescence assisted diagnosis, tumor visualization and the
      establishment of margins during resection.

PMID- 18829177
TI  - Dental implants with the periodontium: a new approach for the restoration of
      missing teeth.
AB  - Tooth loss is a common occurrence in mankind and damages human health.
      Osseointegrated dental implants have been successfully used as a popular
      prosthetic restoration for the missing teeth for many years. However,
      osseointegration, representing a direct connection between the implant and bone
      tissue without the periodontium, causes some inevitable problems, such as
      masticatory force concentration and immobility of the dental implant. Thus, an
      ideal dental implant should have its own peri-implant periodontium, as do the
      natural teeth. A number of attempts have been made to reconstruct the
      periodontium around the implants. Unfortunately, it has been established that a
      predictable periodontal reconstruction, especially the acellular cementum
      reconstruction on the surface of the implant, is a very difficult task. In this
      paper, we propose the hypothesis that the cementum may be a special phenotype of
      the bone tissue, on the basis of its strong similarity in development, structure,
      and function. In a certain condition, the bone tissue may change to cementum for
      special functional needs. In accordance with this hypothesis, we consider a novel
      approach to reconstruct the peri-implant tissues. Unlike previous studies, this
      approach imitates the tooth re-plantation process. The key point is to convert
      the implant-surrounding bone tissues to cementum as a result of adaptive changes
      to the implant-support demands. This hypothesis, if proven to be valid, will not
      only represent a breakthrough in cementum research, but also will open a new door
      to the restoration of missing teeth.

PMID- 18829178
TI  - Role for Porphyromonas gingivalis in the progression of atherosclerosis.
AB  - An association between atherosclerosis and Porphyromonas gingivalis (P.
      gingivalis), a major periodontopathogen, has been shown. However, the question of
      whether this relationship is causal or coincidental still exist. Many individuals
      with evidence of atherosclerosis demonstrate seropositivity to this pathogen.
      Both in vitro studies and in animal models document that P. gingivalis can
      accelerate atheroma deposition. Recently, evidence from diverse sources has
      suggested P. gingivalis can activate host innate immune responses associated with
      atherosclerosis. These studies confirm that the inflammatory response to P.
      gingivalis could exacerbate vascular inflammation via secreted cytokines and/or
      chemokines that ultimately modulate early atherogenesis that spontaneously
      develop atherosclerosis. Meanwhile, the cytokine and chemokines interact in the
      progression of atherosclerosis. Moreover, the reaction of endothelial cells in
      response to P. gingivalis and its various virulence factors are diverse, the
      expression of chemokine differ through different signal transduction pathways
      accordingly. Results from these studies reinforce the connection between P.
      gingivalis and atherosclerosis. Given the role of P. gingivalis in the initiation
      and progression of atherosclerosis, attaching importance to periodontal disease
      may offer new therapeutic options for the management of patients with
      atherosclerosis.

PMID- 18829179
TI  - Ghrelin may reduce radiation-induced mucositis and anorexia in head-neck cancer:
      two sides of a coin.

PMID- 18829180
TI  - A thoracic mechanism of mild traumatic brain injury due to blast pressure waves.
AB  - The mechanisms by which blast pressure waves cause mild-to-moderate traumatic
      brain injury (mTBI) are an open question. Possibilities include acceleration of
      the head, direct passage of the blast wave via the cranium, and propagation of
      the blast wave to the brain via a thoracic mechanism. The hypothesis that the
      blast pressure wave reaches the brain via a thoracic mechanism is considered in
      light of ballistic and blast pressure wave research. Ballistic pressure waves,
      caused by penetrating ballistic projectiles or ballistic impacts to body armor,
      can only reach the brain via an internal mechanism and have been shown to cause
      cerebral effects. Similar effects have been documented when a blast pressure wave
      has been applied to the whole body or focused on the thorax in animal models.
      While vagotomy reduces apnea and bradycardia due to ballistic or blast pressure
      waves, it does not eliminate neural damage in the brain, suggesting that the
      pressure wave directly affects the brain cells via a thoracic mechanism. An
      experiment is proposed which isolates the thoracic mechanism from cranial
      mechanisms of mTBI due to blast wave exposure. Results have implications for
      evaluating risk of mTBI due to blast exposure and for developing effective
      protection.

PMID- 18829181
TI  - Do sleep abnormalities related to disruption of synaptic homeostasis contribute
      to the pathophysiology of post-traumatic mood disorder and suicidal behavior?

PMID- 18829182
TI  - [Activity of tigecycline against pathogen bacteria isolated in respiratory
      infectious disease in Europe. TEST study 2004-2007].
AB  - Tigecycline (TGC), a semisynthetic glycylcycline, has a documented activity on
      Gram+ and Gram- pathogens including oxacillin-resistant (MRSA) and an extended
      spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae. Tigecycline
      Evaluation and Surveillance Trial (TEST) is an international surveillance study
      designed to assess the in vitro activity of TGC and 11 comparators against a
      range of important clinical pathogens from both the community and the hospital.
      The aim of this study was to assess efficacy of TGC, using this database, against
      pathogens implicated in community or hospital pneumonia and sinusitis. A total of
      4163 isolates were consecutively collected in 21 European countries during three
      years (2004-2007). In all center, minimum inhibitory concentration (MIC) were
      determinated with the same Microscan panel (Dade-Behring). Tigecycline exhibited
      a good activity against respiratory pathogens, with the exception of Pseudomonas
      aeruginosa. Hundred percent of cocci Gram+ (Streptococcus pneumoniae,
      Staphylococcus aureus, Enterococcus sp.) and 100% of Haemophilus sp. are
      inhibited with 0.5 mg/L, without effect of an associated beta-lactam resistance
      mechanism. TGC is active in vitro on 89% of Enterobacteriaceae, with MIC 90 less
      or equal to 2mg/L. Eighty-nine percent of Enterobacter sp. and 77% of Serratia
      sp. are susceptible with range of MIC 90 from 2 to 4 mg/L. These interesting
      results obtained in vitro are to be strengthened by clinical studies.

PMID- 18829183
TI  - [Listeria and listeriosis: from farm to fork].
AB  - Listeria monocytogenes is a bacterium widely spread in the environment. Its
      persistence in industrial environment leads to food product contamination from
      the raw materials and constitutes a recurrent problem in food processing industry
      despite the use of cold chain procedures. L. monocytogenes is a foodborne
      pathogen causing severe and life-threatening infections that evolve mainly under
      sporadic mode, even if epidemics sometimes occur. Listeriosis causes mainly
      septicemia, central nervous system infections (meningitis and
      meningoencephalitis) and abortions. Listeriosis occurs primarily at risk groups
      of population like elderly people, pregnant women, neonates and patients with
      underlying diseases or impaired cellular immunity. In France, the epidemiological
      surveillance of listeriosis is based on two complementary approaches: the
      mandatory notification and the microbiological characterization by the National
      Reference Centre for Listeria of L. monocytogenes strains isolated from patients.
      The joined efforts of government and food producers have led to decrease
      significantly the incidence of listeriosis in France since 20 years and the
      number of epidemics. However, the recent observation of increasing number of
      listeriosis cases in most of the industrialised countries calls up to the
      attentiveness to reconsider the current rules and to reinforce the
      epidemiological surveillance of listeriosis in a context where susceptible people
      including the elderly are in increasing number.

PMID- 18829184
TI  - Treated and untreated remission from problem drinking in late life: post
      remission functioning and health-related quality of life.
AB  - OBJECTIVE: To evaluate the post-remission status of older remitted problem
      drinkers who achieved stable remission without treatment. METHOD: The post
      remission drinking behavior, health-related functioning, life context, coping,
      and help-seeking of older, untreated (n=330) and treated (n=120) former problem
      drinkers who had been remitted for a minimum of 6 years were compared twice over
      the course of 6 years to each other and to lifetime nonproblem drinkers (n=232).
      Analyses considered the impact of severity of drinking problem history. RESULTS:
      Untreated remitters were more likely than treated remitters to continue to drink,
      exhibited fewer chronic health problems and less depressive symptomatology, and
      were less likely to smoke. Untreated remitters' life contexts were somewhat more
      benign than those of treated ones, and they were less likely to describe a coping
      motive for drinking and engage in post-remission help-seeking. Although untreated
      remitters more closely resembled lifetime nonproblem drinkers than did treated
      remitters, both untreated and treated remitter groups exhibited worse health
      related functioning, more financial and interpersonal stressors, and more post
      remission help-seeking than did lifetime nonproblem drinkers. CONCLUSIONS:
      Regardless of whether late-life remission was gained without or with treatment,
      prior drinking problems conveyed a legacy of health-related and life context
      deficits.

PMID- 18829185
TI  - Molecular epidemiological investigation of Newcastle disease virus from domestic
      ducks in Korea.
AB  - To expand the epidemiological understanding of Newcastle disease virus (NDV)
      found in domestic ducks in Korea, 14 NDV isolates from apparently healthy
      domestic ducks were biologically and genetically characterized. Thirteen and 1
      isolates of NDV were categorized into lentogenic and velogenic viruses,
      respectively, based on in vivo pathogenicity tests. Twelve lentogenic viruses
      showed HA activity to horse RBCs, while 1 lentogenic virus and the velogenic
      virus were negative. Lentogenic viruses (n=13) had sequence motifs of
      (112)ERQERL(117) (n=1) or (112)GRQGRL(117) (n=12) at the F0 cleavage site, while
      the velogenic virus (n=1) had a sequence motif of (112)RRQKRF(117) at the same
      site. Phylogenetic analysis revealed that at least three distinct genotypes may
      exist in domestic ducks in Korea; one class I genotype (genotype 2), and two
      class II (genotypes I and VII) genotypes. The class I virus was most closely
      related to strains of genotype 2 which were isolated in birds from the USA,
      Germany and Denmark. Twelve lentogenic class II viruses were grouped together in
      genotype I, and were then divided into at least three clusters, namely Aomori
      like, Ulster2C-like, and V4-like. The velogenic class II virus was assigned to
      genotype VII which represents viruses responsible for recent epidemics in many
      Asian countries including Korea. The epidemiological importance of domestic duck
      isolates of NDV in Korea is discussed.

PMID- 18829186
TI  - The neonatal form of Aicardi-Goutieres syndrome masquerading as congenital
      infection.
AB  - Aicardi-Goutieres syndrome (AGS) is a rare, genetically-determined encephalopathy
      whose importance from a neonatology perspective is magnified because of the risk
      of misdiagnosis as the sequelae of congenital infection. Molecular advances have
      shown that AGS can be caused by mutations in any one of at least five genes (four
      of which have been identified). A recent genotype-phenotype study has shown that
      a neonatal form of the disease, highly reminiscent of congenital infection, is
      seen particularly with TREX1 mutations. It seems likely that the enzymes
      defective in AGS are involved in digesting endogenous nucleic acids (DNA and RNA)
      produced during normal cell replication, and that a failure of this removal
      results in inappropriate triggering of the innate immune system. This hypothesis
      explains the remarkable phenotypic overlap of AGS with congenital infection,
      where a similar interferon alpha mediated innate immune response is triggered by
      viral, as opposed to self, nucleic acids.

PMID- 18829187
TI  - Assessment of risk factors for survival of neonates born after second-trimester
      PPROM.
AB  - OBJECTIVE: Assess fetal risk factors which impact survival of infants delivered
      after second-trimester PPROM. STUDY DESIGN: Clinical records of 87 patients, who
      all had second-trimester rupture of membranes between 14+0 and 24+6 weeks of
      gestation treated January 1998 to July 2005 were reviewed regarding perinatal
      outcome. This study is based on 25 surviving infants. RESULTS: 13 of these 25
      infants died in the hospital. Survivors had a higher birth weight (p=0.008) and
      higher Apgar scores after 5 min (p=0.005) than those infants dying. No
      differences in UA pH, the need of catecholamines and no association between
      histological verified chorioamnionitis and early onset sepsis were seen between
      survivors and nonsurvivors. CONCLUSION: Higher gestational age at birth, higher
      birth weight, the absence of histologically verified chorioamnionitis and 5 min
      Apgar scores of >or= than 6 have positive prognostic value for survival of
      neonates delivered preterm after second-trimester PPROM.

PMID- 18829188
TI  - Four million newborn deaths: is the global research agenda evidence-based?
AB  - Four million neonates die each year. These deaths are mostly in low-income
      countries, but neonatal mortality and morbidity are also a priority burden in
      high-income countries. Epidemiological evidence suggests newborn research would
      prioritise the poorest families; birth and the first days of life; major causes
      particularly infections, preterm birth and asphyxia; and include preventive
      strategies as well as improved care. However research investment is not
      commensurate to burden, and there is a mismatch with current research priorities.
      South Asia and sub Saharan Africa, with 75% of the burden, expend around US$20
      million per year on newborn research, a fraction of what is spent on a smaller
      proportion of health problem in rich countries. We propose a research pipeline of
      description, discovery, development of solutions and delivery of research with
      scale-up to reach the poorest families. Listing research options and applying
      quantitative scoring enables systematic, transparent research prioritisation. As
      well as a research pipeline, a "people pipeline" is required to generate research
      capacity in low-income countries.

PMID- 18829189
TI  - Changes in concentrations of follistatin in maternal plasma and foetal fluids
      during pregnancy and parturition in sheep.
AB  - Studies have shown that follistatin may be involved in the regulation of ovarian
      development, pregnancy and parturition. The aim of the present study was to
      measure follistatin levels in maternal plasma and foetal fluids during pregnancy
      and parturition in sheep. Using a previously described follistatin
      radioimmunoassay, we found that follistatin in foetal plasma and allantoic fluid
      was higher in the female than in the male at days 50-75 of gestation. Follistatin
      concentrations in maternal plasma declined from -9 to -3h before the completion
      of lamb delivery, and increased from 21 to 39 h after parturition. These results
      suggest that follistatin may play a role in femaleness development, and that
      follistatin may be involved in the mechanism of normal parturition and in
      regulation of the tissue repair after parturition.

PMID- 18829190
TI  - Effects of novel single nucleotide polymorphisms of the FSH beta-subunit gene on
      semen quality and fertility in bulls.
AB  - The follicle-stimulating hormone (FSH) acts on the Sertoli cells in the
      seminiferous tubules of the testis and regulates spermatogenesis up to the
      secondary spermatocyte stage. This study aimed to investigate molecular genetic
      characteristics of the bovine FSH beta-subunit gene (FSHB) and elucidate the
      effects of single nucleotide polymorphisms (SNPs) of FSHB on the quality of fresh
      and frozen semen and on fertility in bulls. We used polymerase chain reaction
      single-strand conformation polymorphism (PCR-SSCP) and sequencing of the FSHB
      gene in 56 bulls belonging to three breeds. We identified 13 substitutions and 1
      insertion in the upstream regulation region and in the coding region of exon 3,
      which were all linked together. Bioinformatics analysis suggested that mutations
      of the 5'-upstream regulation region altered the binding sites for transcription
      factors, and radioimmunoassay demonstrated that mutations may result in
      alterations in the serum FSH concentrations. The least-squares analysis revealed
      that bulls with this genotype exhibited a significantly lower sperm concentration
      in fresh semen and a lower percentage of acrosome integrity in both fresh and
      frozen semen (P<0.05). These bulls also exhibited a significantly higher
      percentage of sperm deformity in fresh semen (P<0.05), which was more pronounced
      in frozen semen (P<0.01), and a significantly lower sperm motility in frozen
      semen (P<0.05). For fertility evaluation, the nonreturn rates obtained from
      14,416 inseminations with the analyzed batches revealed that bulls with this
      genotype showed significantly lower nonreturn rates (P<0.05). In other words,
      bulls with this genotype exhibited lower semen quality, poor freeze resistance,
      and lower fertility. These results suggest that the SNPs in bovine FSHB are
      associated with semen quality and fertility in bulls.

PMID- 18829191
TI  - Stature and gender estimation using foot measurements.
AB  - In forensic investigation difficulties are being experienced in the stature and
      gender estimation of bodies dismembered in mass destruction. So as to eliminate
      these difficulties, new methods are being developed. The aim of this study is to
      develop formulae for estimation of the stature and gender through foot
      measurements when necessary. For this purpose, the length, width, malleol height,
      navicular height measurements of the right and left foot as well as stature have
      been taken from the 249 subjects who are attending Medical Faculty of Dokuz Eylul
      University and School of Physical Therapy and Rehabilitation in Turkey. In males,
      stature and foot measurements were higher than in females, and the difference
      between the average measures was significant. The highest correlation was
      observed in the right and left foot length for female, male and study (mix-gender
      group) groups when stature and foot measurement relations were evaluated. The
      lowest correlation was observed in foot width for the right foot in all groups
      but, differed in left foot measurements for each group. Formulae were obtained by
      using multiple regression analysis for stature estimation and logistic regression
      analysis for gender estimation. As a consequence, whilst stature estimation
      formulae, depending on the gender, allow 9-10 cm errors, those that are
      independent on the gender help make estimation with less than 4 cm errors. Gender
      estimation formula can help determine the gender with 95.6% accuracy via right
      foot measurements, and 96.4% accuracy via left foot measurements. In population
      similar to our subjects, stature and gender estimation can be made by using foot
      measurements.

PMID- 18829192
TI  - A novel technique for automatic shoeprint image retrieval.
AB  - Recent developments in forensic science have resulted in large numbers of scene
      of crime images being collected for recording and analysis. Shoeprint images are
      no exception. In fact, these have recently been of great interest to police and
      forensic scientists as footwear evidence is now treated in the same manner as
      fingerprint and DNA evidence. Traditional approaches to shoeprint representations
      attempt to classify shoeprint images based on a number of possible patterns. Such
      approaches are difficult to implement in an automatic fashion without the
      intervention of a forensic specialist. This paper presents a robust algorithm for
      shoeprint matching based on Hu's moment invariants. It is shown that decreasing
      the resolution of images does not have a significant effect on the performance of
      the algorithm. It is also shown that the optimal performance of the proposed
      system is attained for images rotated by any angle.

PMID- 18829193
TI  - Dynamic optical breast imaging: a novel technique to detect and characterize
      tumor vessels.
AB  - PURPOSE: To prospectively determine the diagnostic accuracy of optical absorption
      imaging in patients with Breast Imaging Reporting and Data System (BI-RADS) 3-5
      breast lesions. MATERIALS AND METHODS: Forty-six patients with BI-RADS
      classification 3 (11%), 4 (44%) or 5 (44%) lesions, underwent a novel optical
      imaging examination using red light to illuminate the breast. Pressure was
      applied on the breast, and time-dependent curves of light absorption were
      recorded. Curves that consistently increased or decreased over time were
      classified as suspicious for malignancy. All patients underwent a core or
      surgical biopsy. RESULTS: Optical mammography showed a statistical difference in
      numbers of suspect pixels between benign (N=12) and malignant (N=35) lesions
      (respectively 1325 vs. 3170, P=0.002). In this population, optical imaging had a
      sensitivity of 74%, specificity of 92%, and diagnostic accuracy of 79%. The
      optical signal did not vary according to any other parameter including breast
      size or density, age, hormonal status or histological type of lesions.
      CONCLUSION: Optical imaging is a low-cost, non-invasive technique, yielding
      physiological information dependent on breast blood volume and oxygenation. It
      appears to have a good potential for discriminating benign from malignant
      lesions. Further studies are warranted to define its potential role in breast
      cancer imaging.

PMID- 18829194
TI  - The radiotherapy clinical trials projects at the ESRF: technical aspects.
AB  - The radiotherapy clinical trials projects, both aiming at treating aggressive
      brain tumors, require several major modifications and new constructions at the
      ESRF ID17 Biomedical beamline. The application of the Stereotactic Synchrotron
      Radiation Therapy (SSRT) technique mainly necessitates an upgrade of the existing
      patient positioning system, which was formerly used for the angiography program.
      It will allow for accurate positioning, translation and rotation of the patient
      during the treatment. For the Microbeam Radiation Therapy (MRT) clinical trials
      project, a new white beam hutch will be constructed to accommodate a dedicated
      patient positioning system. Consequently, the existing control hutches and the
      related installations will also be completely refurbished. Furthermore, the
      foreseen installation of a second X-ray source, which will allow doubling the
      currently available photon flux at high energies, requires a redesign of most
      optical components to handle the increased power and power densities. Starting
      from the current ID17 Biomedical beamline layout, the paper will present an
      update of the different modification/construction projects, including the general
      organization and planning.

PMID- 18829195
TI  - Liver metastases of neuroendocrine carcinomas: interventional treatment via
      transarterial embolization, chemoembolization and thermal ablation.
AB  - The aim of this review article is to provide a practical clinical guideline for
      indication, technical aspects, protocol guideline and strategies for the
      interventional treatment of liver metastases from neuroendocrine tumors and
      focusing on the results of various protocols of management. The response to
      therapy, in the published articles, is calculated on the basis of the following
      clinical parameters; including symptomatic response (SR), biologic response (BR),
      morphological response (MR), progress free survival (PFS), and survival periods
      (SP). Transarterial chemoembolization (TACE) has been associated with SR rates of
      60-95%, BR of 50-90%, MR of 33-80%, SR of 20-80 months, and a 5-year survival of
      between 50% and 65%. PFS was also between 18 and 24 months. In the transarterial
      embolization (TAE) group, SR was similar to the TACE group, MR was 32% and 82%,
      survival was between 18 and 88 months with a survival rate of 40-67%, and BR was
      between 50% and 69%. Radiofrequency ablation (RFA), either percutaneous or during
      surgery, has been associated with SR of 71-95% for a mean duration of 8-10
      months, BR of 65%, and mean SP of 1.6 years after ablation. The mean survival
      following surgical resection for operable cases is 4.26 years+/-S.D.: 1.1.
      CONCLUSION: The interventional protocols for the management of liver metastases
      from neuroendocrine tumors: for oligonodular liver metastatic deposits, local
      resection or RFA and/or LITT is recommended, while in multinodular diseases with
      higher tumor load, TACE or TAE is recommended.

PMID- 18829196
TI  - Morphological and functional MRI, MRS, perfusion and diffusion changes after
      radiosurgery of brain metastasis.
AB  - Radiosurgery is a noninvasive procedure where spatially accurate and highly
      conformal doses of radiation are targeted at brain lesions with an ablative
      intent. Recently, radiosurgery has been established as an effective technique for
      local treatment of brain metastasis. After radiosurgery, magnetic resonance (MR)
      imaging plays an important role in the assessment of the therapeutic response and
      of any complications. The therapeutic approach depends on the imaging findings
      obtained after radiosurgery, which have a role in the decision making to perform
      additional invasive modalities (repeat resection, biopsy) to obtain a definite
      diagnosis and to improve the survival of patients. Conventional MR imaging
      findings are mainly based on morphological alterations of tumors. However, there
      are variable imaging findings of radiation-induced changes including radiation
      necrosis in the brain. Radiologists are sometimes confused by radiation-induced
      injuries, including radiation necrosis, that are seen on conventional MR imaging.
      The pattern of abnormal enhancement on follow-up conventional MR imaging closely
      mimics that of a recurrent brain metastasis. So, classifying newly developed
      abnormal enhancing lesions in follow-up of treated brain metastasis with correct
      diagnosis is one of the key goals in neuro-oncologic imaging. To overcome
      limitations of the use of morphology-based conventional MR imaging, several
      physiological-based functional MR imaging methods have been used, namely
      diffusion-weighted imaging, perfusion MR imaging, and proton MR spectroscopy, for
      the detection of hemodynamic, metabolic, and cellular alterations. These imaging
      modalities provide additional information to allow clinicians to make proper
      decisions regarding patient treatment.

PMID- 18829197
TI  - A highly sensitive radial diffusion measurement method for white matter tract
      investigation.
AB  - This article describes a novel approach for local estimation of the radial
      diffusion coefficient (D(perpendicular)) in white matter (WM) regions containing
      well-oriented nervous fibers. The method is based on the assumption that the
      diffusion process in well-organized WM regions responds to a cylindrical
      symmetry. The increased precision in the estimation of D(perpendicular) provided
      by this local approach compared to standard techniques based on diffusion tensor
      imaging is demonstrated using numerical simulations. An in vivo validation of the
      technique is also provided, showing its application to the corpus callosum of six
      healthy volunteers, highlighting the sensitivity of the method. Assuming that
      D(perpendicular) is sensitive to myelin integrity, our technique has the
      potential to investigate pathophysiological aspects of several neurological and
      psychiatric disorders with improved precision in targeted WM tracts.

PMID- 18829198
TI  - Structural elucidation of a PDE-5 inhibitor detected as an adulterant in a health
      supplement.
AB  - A PDE-5 inhibitor was detected and isolated from a health supplement claimed to
      be a preparation of fresh oyster extracts and be able to promote and support
      healthy sexual function and endurance, etc. The structure of this PDE-5 inhibitor
      was elucidated using LC-UV, LC-TOF-MS, MS-MS, IR spectroscopy, and 2D NMR. It was
      characterized as 8-(2-(4-(hydroxymethyl)piperidin-1-yl)benzylamino)-3-ethyl-1H
      imidazo[4,5-g]quinazoline-2(3H)-thione, a compound reported to be a PDE-5
      inhibitor.

PMID- 18829199
TI  - Quantitative determination of clopidogrel active metabolite in human plasma by LC
      MS/MS.
AB  - A quantitative method for the determination of clopidogrel active metabolite (AM)
      in human plasma was developed and validated using liquid chromatography-tandem
      mass spectrometry (LC-MS/MS). Clopidogrel AM contains a thiol group, thus
      requiring stabilization in biological samples. The alkylating reagent 2-bromo-3'
      methoxyacetophenone was used to stabilize clopidogrel AM in blood. An analog of
      the derivatized clopidogrel AM was used as the internal standard (IS). The
      derivatized samples were subjected to solid-phase extraction with a C2 disk plate
      and the overall procedure exhibited good reaction (more than 90%) and recovery
      efficiencies (from 85% to 105%). The derivative of clopidogrel AM (MP-AM) and IS
      were separated on an ODS column and quantified by tandem mass spectrometry with
      electrospray ionization. No significant endogenous peaks corresponding to MP-AM
      or IS were detected in blank human plasma samples, and no significant matrix
      effect was observed for MP-AM and IS in human plasma samples (from 102% to 121%).
      The calibration curve ranged from 0.5 to 250 ng/mL with good linearity, and
      extended by validation of a 50-fold dilution. In the intra- and inter-assay
      reproducibility tests, the accuracy and precision were within 12% relative error
      and 6% coefficient of variation, respectively. The derivatized MP-AM was stable
      in human plasma for 4 months at -80 degrees C. The validated method was
      successfully used to analyze clinical samples and determine the pharmacokinetics
      of clopidogrel AM.

PMID- 18829200
TI  - Extraction and determination of 2-pyrazoline derivatives using liquid phase
      microextraction based on solidification of floating organic drop.
AB  - A simple, rapid and efficient microextraction method for the extraction and
      determination of some 2-pyrazoline derivative compounds in aqueous samples was
      developed. Microliter volumes of 1-undecanol were delivered to the surface of the
      aqueous sample and the sample was agitated for a desire time. The sample vial was
      cooled by inserting it into an ice bath for 5 min. The solidified solvent was
      transferred into a suitable vial and immediately melted. One microL of the
      organic solvent was injected into a gas chromatography (GC) for analysis. Several
      factors affecting the microextraction efficiency such as sampling temperature,
      stirring rate, pH, nature and volume of the organic solvent and extraction time
      were investigated and optimized values were obtained as 70 degrees C, ,1250 rpm,
      5.0, 8.0 microL (1-undecanol) and 30 min, respectively. Under the optimal
      conditions, detection limits of the method for determination of the compounds
      were in the range of 5-10 microgL(-1). The relative standard deviations (RSDs%)
      for the extraction and determination of the analytes at the concentration level
      of 250 microgL(-1) were in the range of 3.0-11.4. Dynamic linear ranges of 25-800
      microgL(-1) with correlation coefficients in the range of 0.9857<r(2)<0.9968 were
      observed. After 30 min of extraction duration, the enrichment factors varied from
      183 to 538. Finally, the study was applied to the determination of the compounds
      in several real samples including serum and urine and satisfactory results were
      obtained.

PMID- 18829201
TI  - Emergency department medication lists are not accurate.
AB  - BACKGROUND: Medication errors are a common source of adverse events. Errors in
      the home medication list may impact care in the Emergency Department (ED), the
      hospital, and the home. Medication reconciliation, a Joint Commission
      requirement, begins with an accurate home medication list. OBJECTIVE: To evaluate
      the accuracy of the ED home medication list. METHODS: Prospective, observational
      study of patients aged > 64 years admitted to the hospital. After obtaining
      informed consent, a home medication list was compiled by research staff after
      consultation with the patient, their family and, when appropriate, their pharmacy
      and primary care doctor. This home medication list was not available to ED staff
      and was not placed in the ED chart. ED records were then reviewed by a physician,
      blinded to the research-generated home medication list, using a standardized data
      sheet to record the ED list of medications. The research-generated home
      medication list was compared to the standard medication list and the number of
      omissions, duplications, and dosing errors was determined. RESULTS: There were 98
      patients enrolled in the study; 56% (55/98, 95% confidence interval [CI] 46-66%)
      of the medication lists for these patients had an omission and 80% (78/98, 95% CI
      70-87%) had a dosing or frequency error; 87% of ED medication lists had at least
      one error (85/98, 95% CI 78-93%). CONCLUSION: Our findings now add the ED to the
      list of other areas within health care with inaccurate medication lists.
      Strategies are needed that support ED providers in obtaining and communicating
      accurate and complete medication histories.

PMID- 18829202
TI  - Comparison of mortality due to severe multiple trauma in two comprehensive models
      of emergency care: Atlantic Pyrenees (France) and Navarra (Spain).
AB  - BACKGROUND: Injury due to external causes is an important health problem in our
      society today. Emergency care systems based on the concept of "comprehensive
      care" can prevent deaths and disabilities as well as limit the severity and pain
      caused by trauma. OBJECTIVE: To investigate the frequency and characteristics of
      different mechanisms of injury and to estimate mortality, comparing two
      comprehensive emergency systems: Atlantic Pyrenees (AP) in France and Navarra
      (NA) in Spain. MATERIAL AND METHODS: A prospective cohort study of severe
      multiple-injury patients attended to by the comprehensive emergency care systems
      of AP and NA from April 1, 2001 to March 31, 2002. Data were collected from
      personal patient data, the emergency coordination center "112," pre-hospital and
      hospital health care levels, and discharge data. Bivariate statistical analysis
      and multivariate logistic regression models were employed for statistical
      management. RESULTS: There were 614 severe multiple trauma patients recorded, 278
      in AP and 336 in NA. Significant differences were observed in arrival time, pre
      hospitalization care, pre-hospital Revised Trauma Score (RTS), Injury Severity
      Score (ISS) at the intensive care unit, and procedures used (intubation,
      administration of fluids, immobilization, and diagnostic methods). Logistic
      regression showed significant differences in patient death, age (odds ratio [OR]
      1.02, 95% confidence interval [CI] 1.01-1.03), penetrating or accidental
      injuries, (OR 3.85, 95% CI 1.1-13.1), RTS (OR 0.58, 95% CI 0.5-0.7), and ISS
      score (OR 1.05, 95% CI 1.0-1.1). CONCLUSION: Despite a more aggressive approach
      and employment of greater resources, the French comprehensive trauma system does
      not show greater survival rates among injured patients compared to Navarra, even
      when controlling for confounding factors like age, injury mechanism, RTS, ISS,
      and others.

PMID- 18829203
TI  - "Forgettable" sex: a case of transient global amnesia presenting to the emergency
      department.
AB  - BACKGROUND: Transient global amnesia is characterized by the sudden development
      of dense anterograde amnesia, without alteration in level of consciousness and in
      the absence of focal neurologic deficits or seizure activity. Various
      precipitating causes have been reported in the medical literature. OBJECTIVE: To
      present a literature-guided approach to the diagnosis and management of transient
      global amnesia in the Emergency Department (ED). CASE REPORT: We report the case
      of a 54-year-old woman who presented to the ED with an episode of acute memory
      loss. CONCLUSIONS: Although rare, transient global amnesia may present in a
      dramatic fashion. The occurrence of a distinct precipitating event and repetitive
      questioning seem to be key features in making the diagnosis. Important
      differential considerations include transient ischemic attack, seizure, and
      subarachnoid hemorrhage. Brain imaging and specialty consultation are reserved
      primarily for patients with unclear circumstances, altered level of
      consciousness, focal neurologic findings, and persistent (or very brief) amnestic
      symptoms. Brain imaging may, however, relieve anxiety about more dangerous causes
      of the event.

PMID- 18829204
TI  - A formula for the stratified selection of patients with paroxysmal atrial
      fibrillation in the emergency setting: a retrospective pilot study.
AB  - BACKGROUND: Amiodarone is a commonly used medication in the treatment of atrial
      fibrillation (AF) of recent onset. STUDY OBJECTIVES: The aim of the study was to
      identify a possible formula for selecting Emergency Department (ED) patients with
      paroxysmal AF who will spontaneously restore sinus rhythm (SR), successfully
      restore SR with the use of loading intravenous (i.v.) amiodarone, or require 24-h
      maintenance amiodarone infusion. METHODS: This retrospective pilot study included
      141 patients with recent-onset AF. Patients who did not restore SR spontaneously
      received i.v. amiodarone (5 mg/kg) within a period of 30 min. In case of no
      response, an additional dosage of 1000 mg of i.v. amiodarone was administered
      over a period of 24 h. Binary logistic regression models were used to determine
      the predictors of spontaneous conversion and the response to amiodarone
      administration. RESULTS: The formula ([heart rate/systolic blood pressure] + 0.1
      * number of past AF incidences) was chosen as the one with the highest combined
      sensitivity and specificity. This index identified the patients who spontaneously
      restored SR (cutoff point 1.31 with 78.6% sensitivity and 77.9% specificity),
      whereas for patients who responded to the loading i.v. amiodarone dose, the use
      of the index (cutoff point 1.24) exhibited 84.1% sensitivity and 75.3%
      specificity. CONCLUSIONS: This formula may be a useful and reliable bedside
      diagnostic tool to identify AF patients most likely to spontaneously convert, or
      respond to loading amiodarone administration in the emergency setting. The use of
      this index also can assist in patient risk stratification.

PMID- 18829205
TI  - Impact of a subcutaneous insulin protocol in the emergency department: Rush
      Emergency Department Hyperglycemia Intervention (REDHI).
AB  - OBJECTIVE: We evaluated a hyperglycemia treatment protocol for use in the
      Emergency Department (ED) in patients with diabetes mellitus (DM) before
      admission to the hospital or discharge home. METHODS: Fifty-four consecutive
      patients with a history of DM and an ED admission blood glucose (BG) > 200 mg/dL
      were treated with subcutaneous (SQ) insulin aspart every 2 h until BG was < 200
      mg/dL. Point-of-care BG was measured immediately on ED admission and every 2 h
      until discharge home or hospital admission. The intervention group was compared
      with 54 historical controls with DM and an ED admission BG > 200 mg/dL. RESULTS:
      One hundred percent of intervention patients received insulin aspart, whereas
      only 35% of historical controls received insulin therapy. In the intervention
      group, mean BG declined from 333 +/- 104 mg/dL on ED admission to 158 +/- 68
      mg/dL on ED discharge. In the historical control group, mean BG decline was
      significantly less, from 322 +/- 126 mg/dL on admission to 242 +/- 79 mg/dL on
      discharge (p < 0.001). Sixty-nine percent of intervention patients and 67% of
      controls were subsequently admitted to the hospital. Mean hospital length of stay
      (LOS) in the intervention group was significantly less, 3.8 +/- 3.3 days,
      compared with 5.3 +/- 4.1 days in the control group (p < 0.05). Four intervention
      patients (7.4%) developed a BG < 70 mg/dL. CONCLUSION: A protocol for the
      treatment of acute hyperglycemia in the ED can be safely implemented. Subsequent
      inpatient LOS was reduced. Further randomized clinical trials of this
      intervention are warranted.

PMID- 18829206
TI  - An innovative approach to orotracheal intubations: the Alexandrou Angle of
      Intubation position.
AB  - Visualization of the vocal cords is paramount during orotracheal intubations. We
      employed a novel patient position in this derivation study. The Alexandrou Angle
      of Intubation (AAI) position is defined as a 20 degrees -30 degrees  incline
      where the supine patient's head is elevated in relation to the body and legs. Our
      study participants were blinded to the goals of the research as well as our novel
      technique. Using intubation manikins, our participants ranked their preference
      for visualizing the vocal cords between the Flat, Trendelenburg, and AAI
      positions. A majority (58.8%) of our study participants preferred the AAI for
      visualizing the vocal cords over the other two positions. Future studies will
      reveal whether AAI will play a significant role in emergent airway management.

PMID- 18829207
TI  - Transabdominal impalement: absence of visceral or vascular injury a rare
      possibility.
AB  - BACKGROUND: Abdominal impalement injuries are usually associated with visceral
      and vascular injury, causing significant morbidity and mortality. The management
      of these injuries poses specific challenges in prehospital care, transport, and
      management strategies. OBJECTIVE: We report a case of transabdominal impalement
      with no injury to intra-abdominal visceral or vascular structures, demonstrating
      a chance occurrence. The literature regarding abdominal impalement injury is
      reviewed and the management of these injuries is discussed. CASE REPORT: A 35
      year-old man with a transabdominal impalement injury after an accidental fall
      from a tree on to a wooden fence was brought to the Accident and Emergency
      Department. The wooden fence piece was impaled and in situ. Laparotomy revealed
      no intra-abdominal visceral or vascular injury. CONCLUSION: Transabdominal
      impalement injuries pose peculiar challenges in prehospital care, transport to
      hospital, and management. Operative intervention is required in all cases for a
      conclusive and safe management, as the possibility of escaping intra-abdominal
      injury is very rare.

PMID- 18829208
TI  - The oblique view: an alternative approach for ultrasound-guided central line
      placement.
AB  - BACKGROUND: Numerous studies have shown significant benefits of using real-time
      ultrasonography for central line intravenous access. Traditionally, the
      ultrasound probe is placed along the short axis of the vein to visualize and
      direct needle placement. This view has some limitations, particularly being able
      to visualize the needle tip. Some practitioners place the ultrasound probe in the
      long axis of the vessel to direct needle placement, allowing better visualization
      of the needle entering the vein, but this does not allow visualization of
      relevant anatomic structures. OBJECTIVES: We describe an alternative means to
      obtain ultrasound-guided vascular access using an oblique axis rather than the
      traditional short-axis approach. DISCUSSION: This view allows better
      visualization of the needle shaft and tip but also offers the safety of being
      able to visualize all relevant anatomically significant structures at the same
      time and in the same plane. This orientation is halfway between the short and
      long axis of the vessel, allowing visualization of the needle as it enters the
      vessel. This capitalizes on the strengths of the long axis while optimizing short
      axis visualization of important structures during intravenous line placement.
      CONCLUSION: Ultrasound-guided vascular access can be obtained in a variety of
      ways. We describe a technique that is used by some experienced ultrasound users
      but that has never been fully described in the literature. This technique for
      obtaining ultrasound-guided vascular access offers another option for attempting
      ultrasound-guided vascular access that has the potential to improve success rates
      and minimize complications associated with intravenous access.

PMID- 18829209
TI  - Delayed post-endoscopic retrograde cholangiopancreatography perforation
      presenting as scrotal subcutaneous emphysema.

PMID- 18829210
TI  - OTIS: a promising tool that needs to be evaluated in large studies.

PMID- 18829211
TI  - Advance directives based on cognitive therapy: a way to overcome coercion related
      problems.
AB  - OBJECTIVE: Mental health advance directives (ADs) are potentially useful for
      bipolar patients due to the episodic characteristic of their disease. The aim of
      the present study is to evaluate the impact of advance directives based on
      cognitive therapy (ADBCT) on the number and duration of hospitalizations as well
      as compulsory admissions and seclusion procedures. METHOD: Charts of all
      treatment non-adherent patients and committed patients who wrote their ADs
      following an ADBCT intervention within a 24 months period prior to the beginning
      of the study were included. Number and duration of psychiatric hospitalizations
      for a mood or a psychotic episode as well as compulsory admissions and seclusion
      procedures were recorded for each patient 2 years before ADBCT and during a
      follow-up period of at least 24 months. RESULTS: The number of hospitalizations,
      the number of compulsory admission procedures and the number of days spent in
      psychiatric hospital reduced significantly after ADCBT in comparison to the 2
      years who preceded this intervention. CONCLUSION: This retrospective data suggest
      that ADBCT is effective for patients with compliance and coercion problems.
      However, these results need to be confirmed in randomized controlled trials.
      PRACTICE IMPLICATIONS: ADBCT seems to be a useful approach for treatment-non
      adherent and previously coerced patients.

PMID- 18829213
TI  - Customer quality in health care.

PMID- 18829212
TI  - Patient education combined in a music and habit-forming intervention for
      adherence to continuous positive airway (CPAP) prescribed for sleep apnea.
AB  - OBJECTIVE: As many as 50% of patients diagnosed with obstructive sleep apnea stop
      adhering to the prescribed medical treatment of continuous positive airway
      pressure (CPAP) within 1-3 weeks of onset. Thus, a theory-based intervention
      using music to support habit formation was designed to improve CPAP adherence at
      onset. The intervention materials included directions for CPAP nightly use, a
      diary for recording nightly use and writing about CPAP benefits or problems. In
      addition, an audiotape with softly spoken instructions for placing the CPAP mask
      comfortably, using deep breathing and muscle relaxation along with the slowly
      decreasing music tempo was provided to listen to at bedtime each night. METHODS:
      Effects of this music intervention were tested in a randomized, placebo
      controlled trial of 97 patients with 53 males (55%) and 44 females (45%).
      Moderate to severe apnea/hyponea scores (per sleep laboratory data) and medical
      diagnosis of OSA were required for study inclusion. RESULTS: Compared to placebo
      controls, a greater proportion of experimental patients were adhering
      (chi(2)=14.67, p<0.01; a large difference, Phi=0.39) at the end of the first
      month of CPAP onset. There were no differences in CPAP adherence at 3
      (X(2)=0.065, p=0.79) and 6 (X(2)=.118, p=0.73) months. Patients' diary data and
      satisfaction survey results indicated the intervention was rated as helpful and
      guided formation of a relaxing, habitual routine of CPAP nightly use. CONCLUSION:
      The intervention had a strong effect for improving adherence to CPAP at 1 month.
      PRACTICE IMPLICATIONS: Adherence at the onset of treatment is critical and the
      audio music intervention was easily administered. Other interventions that target
      problems interfering with longer-term CPAP adherence are needed.

PMID- 18829214
TI  - Effect of chronic renal insufficiency on outcomes of carotid endarterectomy.
AB  - OBJECTIVE: Conflicting data exist regarding the effect of chronic renal
      insufficiency (CRI) on carotid endarterectomy (CEA) outcomes. A large database
      was used to analyze the effect of CRI, defined by glomerular filtration rate
      (GFR), as an independent risk factor of CEA. METHODS: Prospectively collected
      data regarding CEAs performed at 123 Veterans Affairs Medical Centers as part of
      the National Surgical Quality Improvement Program were retrospectively analyzed.
      Renal function was used to divide patients into three CRI groups: normal or mild
      (control; GFR >/=60 mL/min/1.73 m(2)), moderate (GFR 30 to 59), and severe (GFR
      <30). Bivariate analysis and multivariate logistic regression were used to
      characterize risk factors and their associations with 30-day morbidity and
      mortality. RESULTS: Between Jan 1, 1996, and Dec 31, 2003, 22,080 patients
      underwent CEA. Patients missing creatinine levels, already dialysis-dependent, or
      in acute renal failure just before surgery were excluded. This left 20,899
      available for analysis, of which 13,965 had a GFR of >/=60, 6,423 had a GFR of 30
      to 59, and 511 had a GFR of <30. The incidence of neurologic complications did
      not differ significantly (control, 1.7%; moderate CRI, 1.9%; severe CRI, 2.7%).
      The moderate CRI group experienced significantly more cardiac events (1.7% vs
      0.9% for controls, P < .001). This remained predictive in the multivariate model
      even adjusting for all other risk factors (adjusted odds ratio [AOR], 1.6; 95%
      confidence interval [CI], 1.1-2.3; P = .009). The moderate CRI group also had
      higher rates of pulmonary complications (2.1% vs 1.3% control; P < .001; AOR,
      1.3; 95% CI, 1.0-1.7; P = .031) but not 30-day mortality (P = .269). Those with
      severe CRI had a much higher mortality (3.1% vs 1.0% control, P < .001), which
      remained significant in the multivariate model (AOR, 2.7; 95% CI, 1.6-4.8; P <
      .001). CONCLUSION: Although impaired renal function does not independently
      increase the risk of neurologic or infectious complications, CRI is a significant
      negative independent risk factor in predicting other outcomes after CEA. Patients
      with moderate CRI (GFR, 30-59 mL/min/1.73 m(2)) are at increased risk for cardiac
      and pulmonary morbidity, but not death, and those with severe CRI (GFR <30
      mL/min/1.73 m(2)) have a much higher operative mortality. Patients with CRI
      should be carefully evaluated before CEA to optimize existing cardiac and
      pulmonary disease. Understanding this increased risk may assist the surgeon in
      preoperative counseling and perioperative management.

PMID- 18829215
TI  - Corridor-based functional performance measures correlate better with physical
      activity during daily life than treadmill measures in persons with peripheral
      arterial disease.
AB  - OBJECTIVE: To compare associations of physical activity during daily life with
      treadmill walking performance and corridor-based functional performance measures
      in persons with lower extremity peripheral arterial disease (PAD). STUDY DESIGN:
      Cross-sectional. SUBJECTS: One hundred fifty-six men and women with PAD who
      completed baseline measurements and were randomized into the study to improve leg
      circulation (SILC) exercise clinical trial. MAIN OUTCOME MEASURES: Participants
      completed a Gardner-Skinner treadmill protocol. Corridor-based functional
      performance measures were the 6-minute walk, walking velocity over four meters at
      usual and fastest pace, and the short physical performance battery (SPPB) (0-12
      scale, 12 = best). Physical activity during daily life was measured continuously
      over 7 days with a Caltrac (Muscle Dynamics Fitness Network, Inc, Torrence,
      Calif) accelerometer. RESULTS: Adjusting for age, gender, and race, higher levels
      of physical activity during daily life were associated with greater distance
      achieved in the 6-minute walk (P trend = .001), faster fast-paced four-meter
      walking velocity (P trend < .001), faster usual-paced four-meter walking speed (P
      trend = .027) and a higher SPPB (P trend = .005). The association of physical
      activity level with maximum treadmill walking distance did not reach statistical
      significance (P trend = .083). There were no associations of physical activity
      with treadmill distance to onset of leg symptoms (P trend = .795). CONCLUSION:
      Functional performance measures are more strongly associated with physical
      activity levels during daily life than treadmill walking measures.

PMID- 18829216
TI  - Deep vein thrombosis resolution is impaired in diet-induced type 2 diabetic mice.
AB  - OBJECTIVE: Type 2 diabetes mellitus results in a procoagulant and thrombogenic
      state that could predispose diabetic individuals to develop venous thrombosis. We
      sought to determine whether diet-induced type 2 diabetes mellitus affects deep
      venous thrombosis (DVT) resolution in a murine model. METHODS: C57Bl/6 mice were
      fed a low-fat or a high-fat diet (n = 10) for 10 weeks, after which DVT was
      created in the inferior vena cava (IVC) by a combination of low flow and
      endothelial damage. The IVC and thrombus were harvested at 1 and 2 weeks.
      Thrombus resolution and neovascularization were investigated through transfemoral
      angiography (n = 10), thrombus size (n = 4) and weight (n = 10), and nitric oxide
      synthase 3 immunoquantification (n = 4). Macrophage content was assessed by CD68
      immunoreactivity (n = 4). The fibrinolytic system (urokinase plasminogen
      activator [uPA] and plasminogen activator inhibitor-1 [PAI-1]) was analyzed by
      Western immunoblotting (n = 6) and immunohistochemistry (n = 4). Total collagen
      was stained by Sirius red. Matrix metalloproteinases (MMP)-2 and MMP-9 activities
      were evaluated by zymography and their expressions by Western immunoblotting (n =
      6) and immunohistochemistry (n = 4). RESULTS: Diabetic mice had significantly
      larger and heavier thrombi at 1 and 2 weeks (P < .05), threefold less
      neovascularization (P < .05), and 35-fold increase in macrophage content (P <
      .01), than control mice 2 weeks after surgery. IVC recanalization was documented
      in 90% of 2-week control mice and in 10% of 2-week diabetic mice (P < .01).
      Increased vein wall collagen and less uPA and more PAI-1 expressions with a
      decreased uPA/PAI-1 ratio (31%, P < .01) were documented at 2 weeks in diabetic
      mice. MMP-2 and MMP-9 activities and expressions were significantly increased in
      diabetic mice at 1 and 2 weeks (P < .05) compared with control mice. CONCLUSION:
      Diet-induced type 2 diabetes may impair DVT resolution through altered
      inflammatory, fibrinolytic, and MMP responses.

PMID- 18829217
TI  - Indocyanine green angiography: a new method to quantify collateral flow in mice.
AB  - OBJECTIVES: Therapeutic augmentation of collateral artery growth (ie,
      arteriogenesis) is of particular clinical interest for improving blood flow in
      vascular occlusive disease. Quantification of collateralization in small animal
      models is difficult, however, and the commonly used technique of laser Doppler
      perfusion imaging (LDPI) has always been criticized. Therefore, a new method,
      termed indocyanine green angiography (ICGA), was established for in vivo imaging
      of arteriogenesis in mice and compared with LDPI. METHOD: Using the accepted
      model of ligation of the left femoral artery of 45 C57BL6 mice, we determined
      arteriogenesis both by LDPI and ICGA, which were applied before and periodically
      after ligation of the left femoral artery (each group n = 7). Collateral artery
      growth within the hind limb was additionally verified by histologic workup.
      RESULTS: Determination of flow by ICGA, as represented by maximal pixel intensity
      (ratio of left/right hind limb) demonstrated a drop from 0.97 +/- 0.06 before
      ligation to 0.11 +/- 0.12 directly after ligation, which recovered to 0.48 +/-
      0.22 after 1 week, to 0.65 +/- 0.11 after 2 weeks, and to 0.59 +/- 0.22 after 3
      weeks (n = 7, P < .05). Similarly, flow determined as the perfusion index (slope
      of pixel intensity, ratio left/right) dropped from 1.18 +/- 0.4 before ligation
      to 0.02 +/- 0.03 immediately after ligation but recovered to 0.08 +/- 0.01 after
      1 week, to 0.17 +/- 0.01 after 2 weeks, and to 0.17 +/- 0.06 after 3 weeks (n =
      7, P < .05). Quantification by LDPI demonstrated a drop from 1.06 +/- 0.06
      (left/right ratio) before ligation to 0.37 +/- 0.03 immediately after ligation.
      In contrast to ICGA, perfusion recuperated completely within 1 week to 1.01 +/-
      0.14 and tended to be even higher in the ligated than in the unligated hind limb
      after 2 (1.09 +/- 0.25) and 3 weeks (1.20 +/- 0.29), pointing towards limitations
      of this technique. Histologic analysis confirmed the significant increase in the
      number of collaterals. The intraindividual ratio increased from 1.0 +/- 0.05
      before ligation to 1.35 +/- 0.10 at 2 weeks and 1.41 +/- 0.08 at 3 weeks after
      ligation (P < .05). CONCLUSION: Our data demonstrate that ICGA represents a
      potent tool for the quantification of collateral flow in small animal models. The
      current standard of LDPI seems to rather represent blood movements within the
      superficial skin but not of the entire hind limb.

PMID- 18829218
TI  - C-reactive protein (CRP) elevation in patients with abdominal aortic aneurysm is
      independent of the most important CRP genetic polymorphism.
AB  - OBJECTIVE: C-reactive protein (CRP) is a marker of cardiovascular disease. The
      objective was to determine if abdominal aortic aneurysm (AAA) and CRP serum
      concentration and its CRP gene are associated. METHODS AND RESULTS: AAA patients
      and AAA negative controls were recruited. CRP concentration was measured and the
      single nucleotide polymorphism (SNP), rs3091244, assessed. AAA cases were divided
      into those measuring 30-55 mm and >55 mm in diameter, to assess correlation of
      CRP with AAA size. A total of 248 (227 male) cases and 400 (388 male) controls
      were included. CRP concentration was higher in cases (385.0 microl/dL [310.4
      442.8] vs 180.3 microl/dL [168.1-196.9]; P < .0001). It was higher in large
      aneurysms (685.7 microl/dL [511.8-1083.0] vs 291.0 microl/dL [223.6-349.6]; P <
      .0001), with significant correlation observed to size (r = 0.37, P < .0001). CC
      was the most common SNP genotype with no difference in distribution (P = .43)
      between cases and controls. No difference existed in CRP for each genotype in the
      overall cohort (P = .17), cases (P = .18) and controls (P = .19). CONCLUSION: The
      results demonstrate that CRP production may be related to the presence of AAA,
      especially in advanced disease. The serum concentration of CRP does not appear to
      be influenced by the functional SNP of the CRP gene, which also appears to have
      no association with AAA formation.

PMID- 18829219
TI  - Randomized trial of balneotherapy associated with patient education in patients
      with advanced chronic venous insufficiency.
AB  - OBJECTIVES: Except for compression therapy, physical therapy has scarcely been
      evaluated in the treatment of chronic venous disorders (CVD). Spa treatment is a
      popular way to administer physical therapy for CVD in France, but its efficacy
      has not been evaluated yet. This study aimed to assess the efficacy of
      balneotherapy associated with patient education, as performed in the spa resort
      of La Lechere, in patients with advanced chronic venous insufficiency (CEAP
      clinical classes C4/C5). METHODS: The study was a randomized controlled trial,
      spa therapy being administered on top of the usual medical care. Evaluation was
      by a blinded independent investigator. Subjects were patients with primary or
      post-thrombotic CVD with skin changes but no active ulcer (C4a, C4b, or C5),
      living in Grenoble area, and willing to undergo a spa treatment course in La
      Lechere. The treated group had the three week spa treatment course in La Lechere,
      soon after randomization; the control group also had a spa treatment, but
      starting at day 365. The treatment consisted of four balneology sessions per day,
      six days a week during three weeks, and three educational workshops. An
      independent follow-up was performed in Grenoble hospital every three months for
      15 months. The main outcome criterion was the severity of the skin changes, as
      evaluated by means of malleolar chromametry. Quality of life, as measured by the
      Chronic Venous Insufficiency Questionnaire 2 scale, a visual analog scale (VAS)
      for leg symptoms, and the occurrence of leg ulcers were used as secondary
      criteria. The year after spa treatment in the treated group was compared with the
      year before spa treatment in the control group. RESULTS: Fifty-nine subjects were
      enrolled (29 in the treatment group and 30 in the control group). No
      statistically significant difference between groups was found at study onset
      regarding age, sex, etiology, CEAP "C" class, and the outcome variables. After
      treatment, chromametry showed significantly decreased pigmentation and erythema
      in the treatment group compared with the controls (P < .01). Quality of life (P <
      .01) and symptoms (P < .001) also improved significantly. These differences
      remained significant after one year follow-up. The control patients improved
      similarly after their own spa treatment (day 450). CONCLUSION: This study shows
      that spa therapy, associating balneotherapy and patient education, is able to
      improve significantly the skin trophic changes of the CVD patients and their CVD
      related quality of life and symptoms. This effect is of large magnitude and
      remains significant one year after the treatment course.

PMID- 18829220
TI  - Integrity of venoarteriolar reflex determines level of microvascular skin flow
      enhancement with intermittent pneumatic compression.
AB  - OBJECTIVE: To investigate whether intermittent pneumatic compression (IPC)
      augments skin blood flow through transient suspension of local vasoregulation,
      the veno-arteriolar response (VAR), in healthy controls and in patients with
      peripheral arterial disease (PAD). METHODS: Nineteen healthy limbs and twenty-two
      limbs with PAD were examined. To assess VAR, skin blood flow (SBF) was measured
      using laser Doppler fluxmetry in the horizontal and sitting positions and was
      defined as percentage change with postural alteration [(horizontal SBF--sitting
      SBF)/horizontal SBF x 100]. On IPC application to the foot, the calf, or both,
      SBF was measured with laser Doppler fluxmetry, the probe being attached to the
      pulp of the big toe. RESULTS: Baseline VAR was higher in the controls 63.8 +/-
      6.4% than in patients with PAD (31.7 +/- 13.4%, P = .0162). In both groups SBF
      was significantly higher with IPC than at rest (P < .0001). A higher percentage
      increase with IPC was demonstrated in the controls (242 +/- 85% to 788 +/- 318%)
      than in subjects with PAD, for each one of the three different IPC modes
      investigated (98 +/- 33% to 275 +/- 72%) with IPC was demonstrated. The SBF
      enhancement with IPC correlated with VAR for all three compression modes (r =
      0.58, P = .002 for calf compression, r = 0.65, P < .0001 for foot compression
      alone, and r = 0.64, P = .0002 for combined foot and calf compression).
      CONCLUSION: The integrity of the veno-arteriolar response correlates with the
      level of skin blood flow augmentation generated with intermittent pneumatic
      compression, indicating that this may be associated with a transient suspension
      of the autoregulatory vasoconstriction both in healthy controls and in patients
      with PAD.

PMID- 18829221
TI  - Incidence of ipsilateral postoperative deep venous thrombosis in the amputated
      lower extremity of patients with peripheral obstructive arterial disease.
AB  - OBJECTIVE: Patients undergoing amputation of the lower limb due to peripheral
      arterial disease (PAD) are at risk of developing deep venous thrombosis (DVT).
      Few studies in the research literature report the incidence of DVT during the
      early postoperative period or the risk factors for the development of DVT in the
      amputation stump. This prospective study evaluated the incidence of DVT during
      the first 35 postoperative days in patients who had undergone amputation of the
      lower extremity due to PAD and its relation to comorbidities and death. METHODS:
      Between September 2004 and March 2006, 56 patients (29 men), with a mean age of
      67.25 years, underwent 62 amputations, comprising 36 below knee amputations (BKA)
      and 26 above knee amputations (AKA). Echo-Doppler scanning was performed
      preoperatively and on postoperative days 7 and 31 (approximately). All patients
      received acetylsalicylic acid (100 mg daily) preoperatively and postoperatively,
      but none received prophylactic anticoagulation. RESULTS: DVT occurred in 25.8% of
      extremities with amputations (10 AKA and 6 BKA). The cumulative incidence in the
      35-day postoperative period was 28% (Kaplan-Meier). There was a significant
      difference (P = .04) in the incidence of DVT between AKA (37.5%) and BKA (21.2%).
      Age >or=70 years (48.9% vs 16.8%, P = .021) was also a risk factor for DVT in the
      univariate analysis. Of the 16 cases, 14 (87.5%) were diagnosed during outpatient
      care. The time to discharge after amputation was averaged 6.11 days in-hospital
      stay (range, 1-56 days). One symptomatic nonfatal pulmonary embolism occurred in
      a patient already diagnosed with DVT. There was no relation between other
      comorbidities and DVT. The multivariate analysis showed no association between
      risk factors and the occurrence of DVT in the amputated extremity. DVT
      ipsilateral to the amputation did not influence the mortality rate (9.7%).
      CONCLUSION: The incidence of DVT in the early postoperative period (<or=35 days)
      was elevated principally in patients aged >or=70 years and for AKA. Patients with
      PAD who have recently undergone major amputations should be considered at high
      risk for DVT, even after hospital discharge. Given the high rate of postoperative
      DVT observed in this study, we now recommend prophylactic anticoagulation for
      these patients, but further study is needed to determine the optimal duration and
      efficacy of this treatment.

PMID- 18829222
TI  - Mortality of ruptured abdominal aortic aneurysm treated with open or endovascular
      repair.
AB  - OBJECTIVES: The study defined the selection criteria used for treatment of
      ruptured abdominal aortic aneurysms (RAAAs) and reviewed results during a 5-year
      period. METHODS: From 2002 on, our tertiary referral center adopted a protocol of
      selective use of endovascular repair for RAAAs. The study included all patients
      with a proven RAAA who were admitted to our hospital from 2002 to 2006. The
      primary outcome measure was surgical mortality. RESULTS: A total of 187 patients
      were admitted with an acute AAA, and an RAAA was confirmed 135 (72%) by computed
      tomography scanning or at laparotomy, and 125 (93%) were treated, 89 by open
      means and 36 by endovascular means. The overall mortality rate was 24% and the
      mortality rate was 13.9% for endovascular repair. Endovascular repair was
      consistently used more often in patients with favorable anatomy and in patients
      who were hemodynamically more stable. There were considerable differences in
      approach between the four consultant vascular surgeons. The overall evaluation
      and inclusion for endovascular treatment increased during the study period.
      CONCLUSIONS: A strict protocol for admission, evaluation, and treatment of RAAA,
      with selective use of endovascular repair, resulted in low mortality rates in our
      center.

PMID- 18829223
TI  - Endovenous laser ablation: venous outcomes and thrombotic complications are
      independent of the presence of deep venous insufficiency.
AB  - OBJECTIVE: We hypothesize that endovenous laser ablation (EVA) therapy is equally
      successful in improving venous insufficiency symptoms in patients with or without
      deep venous insufficiency (DVI). METHODS: From January 2005 through August 2007,
      EVA of the great saphenous vein (GSV) was attempted in 364 patients (460 limbs)
      with symptomatic GSV reflux. The GSV was successfully cannulated and obliterated
      in all but 17 limbs. EVA was performed alone in 308 limbs (69.5%) and with
      phlebectomy or perforator ligation (EVAP) in 135 limbs (30.5%). Venous clinical
      severity scores (VCSS) were recorded preoperatively and at 30, 90, 180, and 360
      days postoperatively. Patients were classified as those with or without DVI based
      on duplex imaging valve closure times at the common femoral vein (CFV) and
      popliteal vein (PV). In a subset of 181 patients undergoing EVA therapy in the
      operating room, perioperative thrombosis prophylaxis was administered based on a
      risk-stratification protocol. Patients were assessed with direct end points
      (VCSS) and indirect end points (vein occlusion rates). RESULTS: Successful
      performance of EVA led to complete saphenous vein ablation in 99.8% at 1 month
      and 95.9% at 1 year. Median VCSS preoperatively was 6 (interquartile range, 5-8),
      generally decreasing over all time points to 4 (interquartile range, 2-5) beyond
      360 days (P < .001). Male gender was independently associated with greater
      improvement in scores with time (P = .019). Changes in VCSS and duration of
      vessel occlusion were equivalent regardless of DVI for both isolated EVA and
      EVAP. For EVAP, the true deep venous thrombosis (DVT) rate was 2.2%, whereas for
      isolated EVA, the rate was 0% (P = .028); the rate of saphenofemoral thrombus
      extension was 5.9% for EVAP vs 7.8% for isolated EVA (P = .554). The use of risk
      adjusted heparin prophylaxis in patients undergoing EVAP did not have a
      significant effect on thrombotic complications. There were no differences in true
      DVT, thrombus extension, or superficial thrombophlebitis between patients with or
      without DVI. Performance of concomitant phlebectomy, DVI, gender, and age had no
      effect on the duration of vessel occlusion. CONCLUSION: EVA produces successful
      ablation and is associated with sustained improvement in VCSS. These outcomes are
      independent of the presence of DVI. Finally, the use of a risk-adjusted
      thrombosis prevention protocol had no effect on the rate of superficial thrombus
      extension from EVA or EVAP in patients undergoing general anesthesia.

PMID- 18829224
TI  - Remote ischemic preconditioning in major vascular surgery.
AB  - Remote ischemic preconditioning is a physiologic mechanism in mammalian species
      whereby brief exposure to nonlethal ischemia in one tissue confers protection
      against a prolonged ischemic insult in a distant tissue. First described almost
      15 years ago, it has been slow to translate into clinical practice. Several
      clinical trials have recently reported that remote ischemic preconditioning
      reduces myocardial injury after major cardiovascular surgery. In addition, a
      randomized trial in patients undergoing open abdominal aortic aneurysm repair
      reported a significant reduction in perioperative myocardial infarctions. Remote
      ischemic preconditioning is easily performed and likely to prove highly cost
      effective. large-scale trials of the technique are warranted in patients
      undergoing major vascular surgery.

PMID- 18829225
TI  - Prevalence of carotid stenosis and silent myocardial ischemia in asymptomatic
      subjects with a low ankle-brachial index.
AB  - OBJECTIVE: Subjects with symptomatic peripheral artery disease (PAD) have an
      elevated prevalence of carotid stenosis and of silent myocardial ischaemia. As
      such, clinical guidelines advocate the detection of sub-clinical vascular disease
      in this population. However, the prevalence of occult vascular disease in
      asymptomatic patients with a low ankle-brachial index (ABI) has not been
      previously evaluated. METHODS: Cross-sectional study in five primary care centres
      for patients' selection and two University Hospitals for further assessment.
      Subjects were 1070 asymptomatic individuals between 60 and 80 years of age with
      at least two cardiovascular risk factors, selected for ankle-brachial index
      measurement. Eighty five subjects with an ABI <0.9 and an equal number of
      controls, matched for age, gender, diabetes, and smoking habit, and with a normal
      ABI, were referred to the Hospital for carotid ultrasound and exercise stress
      tests (EST). Main outcome measures were prevalence of a carotid stenosis >50% and
      an abnormal EST. RESULTS: The prevalence of a low ABI in the overall population
      was 9.1%. A carotid stenosis >50% was detected in 14.3% of the subjects with a
      low ABI and in 4.7% of the control subjects (Odds Ratio [OR]: 3.37; 95%
      Confidence Interval [CI]: 1.04-10.93, P = .033). The prevalence of a positive EST
      test was 16.2% in those with a low ABI and 10.5% in control subjects (OR: 1.65;
      95% CI: 0.63-4.29, P = .309). These prevalences were higher in older subjects, in
      those with hypertension or diabetes, or in those with dyslipidemia. CONCLUSION:
      Our results indicate that in high-risk asymptomatic subjects >60 years of age,
      the presence of an ABI <0.9 identifies a subgroup of the population with an
      increased prevalence of carotid stenosis and of silent myocardial ischemia and,
      as such, are candidates for closer follow-up.

PMID- 18829226
TI  - Histopathological comparison between endofibrosis of the high-performance cyclist
      and atherosclerosis in the external iliac artery.
AB  - INTRODUCTION: High performance athletes, predominantly professional cyclists, can
      develop symptomatic arterial flow restriction in one or both legs during
      exercise. The ischemic symptoms are caused by endofibrosis and/or kinking of the
      external iliac artery. Because these athletes are young and have no classic risk
      factors for atherosclerosis, endofibrosis and atherosclerosis are considered
      different disease entities. We compared histology of endofibrotic lesions from
      young sportsmen with atherosclerotic lesions of the external iliac artery in
      elderly individuals. METHODS AND RESULTS: Nineteen external iliac endarterectomy
      specimens from 18 cyclists (age 29 +/- 8 years) were compared with 42 external
      iliac segments from 22 elderly individuals (82 +/- 10 years). Ten arteries from
      elderly individuals revealed an intimal area that was >or=25% of the area
      encompassed by the internal elastic lamina and were considered atherosclerotic
      lesions. Stenosis was higher in patients (65% [interquartile range 50-75]) than
      in controls (11% [7-24]) (P < .0001). The endofibrotic lesions revealed loose
      connective tissue with moderate to high cellularity. Both in endofibrosis and
      atherosclerosis, most cells in the lesion were smooth muscle actin positive. In
      the endofibrosis specimens, loose fibers of collagen were observed, whereas in
      the atherosclerotic lesions collagen was mostly densely packed. Calcification of
      the lesion was not observed in endofibrotic lesions, whereas calcium deposition
      was observed in 80% of atherosclerotic lesions. Lymphocytes were present in 21%
      of endofibrotic lesions and in 80% of atherosclerotic cases. Macrophages were
      observed in 16% of endofibrotic lesions and in all atherosclerotic plaques.
      Luminal thrombosis was observed in one case of endofibrosis. CONCLUSION: In the
      external iliac artery, atherosclerotic lesions and endofibrotic lesions of high
      performance cyclists have distinct morphologic characteristics. Endofibrosis in
      the external iliac artery may serve as soil for luminal thrombosis.

PMID- 18829227
TI  - Cost per day of patency: understanding the impact of patency and reintervention
      in a sustainable model of healthcare.
AB  - BACKGROUND: Healthcare resource utilization is an understudied aspect of vascular
      surgery. Initial cost of a given procedure is not an accurate reflection of
      resource utilization because it does not account for procedural durability and
      efficacy. Herein we describe an amortized cost model that accounts for procedural
      costs, durability, and re-intervention costs. METHODS: A cost model was developed
      using patency data endpoints and total hospital costs (direct and indirect)
      associated with an inital revascularization and subsequent re-interventions. This
      model was applied to a retrospective database of femoropopliteal reconstructions.
      One hundred and eighty-three open cases were compared with 198 endovascular
      cases; and the endpoints of initial cost, amortized cost at 12 months, and
      assisted patency were examined. RESULTS: The open and endovascular cases were not
      statistically different with respect to indication, patient co-morbid profiles,
      or post-procedural pharmacotherapy. Primary assisted patency was better in the
      open revascularization group at 12 months (78% versus 66%, P < .01). There was a
      statistically significant higher initial cost for open reconstruction when
      compared with endovascular ($12,389 +/- $408 versus $6,739 +/- $206, P < .001).
      However, at 12 months post-procedure, the initial cost benefit was lost for
      endovascular patients ($229 +/- $106 versus $185 +/- $124, P = .71). There was,
      however, a trend for endovascular cost savings in claudicants, though this did
      not reach significance ($259 +/- $189 versus $86 +/- $52, P = .31). For patients
      with critical limb ischemia, renal dysfunction, and end stage renal disease, the
      trend favored open surgery. CONCLUSIONS: An amortized cost model provides insight
      into the healthcare resource utilization associated with a particular
      revascularization and assistive procedures. The initial cost savings of
      endovascular therapies are not sustained over time. Cost-savings trends were
      noted, however, longer follow-up is required to see if these will reach
      statistical significance.

PMID- 18829228
TI  - Altered fibrin clot structure and function in the healthy first-degree relatives
      of subjects with intermittent claudication.
AB  - OBJECTIVE: Studies report clustering of cardiovascular risk factors and increased
      cardiovascular events in healthy first-degree relatives (FDR) of subjects with
      intermittent claudication (IC). Family history is an independent risk factor in
      coronary artery disease but the role of genetic factors is undefined in
      peripheral arterial disease. The fibrin clot is the final product of the
      atherothrombotic process and is subject to genetic influence. We proposed that
      healthy male FDR of subjects with IC possess abnormalities in their fibrin clots.
      METHODS: This was a case-control family study. The FDR were recruited from
      claudicants attending vascular surgery out-patient clinics with the control
      subjects being recruited from the local primary care register. A total of 106
      white European male FDR of male subjects with IC were age matched with 107 white
      European male control subjects from an identical geographic area. The control
      subjects had no FDR with a history of symptomatic cardiovascular disease, and
      subjects from both groups were free from a personal history of symptomatic
      cardiovascular disease or diabetes mellitus. Ex vivo assays for fibrin clot
      permeation, fiber thickness, factor XIII cross-linking activity, and fibrinolysis
      were performed on the plasma of the above subjects. In addition, linear
      regression analysis was undertaken to determine factors associated with clot
      parameters. RESULTS: For controls and FDR, respectively, fiber thickness by
      turbidity was 0.75 (0.67-0.93) vs 0.86 (0.75-0.98) (P < .001), and FXIII cross
      linking activity was 105% (87-141) vs 133% (103-155) (P < .001). On confocal
      microscopy, fibers measured 315.8 (307.0-324.6) vs 405.1 (397.6-412.6) nm (P <
      .001), and lysis front velocity was 12.66 (6.38-18.94) vs 4.83 (2.50-7.17),
      mum/min (P = .018). Linear regression analysis revealed cholesterol was
      associated with changes in certain clot parameters. CONCLUSION: The healthy FDR
      of subjects with IC produce clots which have thicker fibers, increased cross
      linking, and resistance to fibrinolysis when compared to controls. This supports
      the potential genetic basis of peripheral arterial disease and highlights that
      cholesterol may contribute to this abnormal structure. This suggests that the FDR
      of subjects with IC, an apparently healthy sub-group of the population, have an
      elevated cardiovascular risk associated with abnormalities in their clot
      structure.

PMID- 18829229
TI  - Regulation of vascular smooth muscle cell expression and function of matrix
      metalloproteinases is mediated by estrogen and progesterone exposure.
AB  - OBJECTIVE: Postmenopausal women receiving hormone replacement therapy (HRT) have
      been reported to have more adverse outcomes after vascular reconstructions,
      including increased intimal hyperplasia development and bypass graft failure. HRT
      may be affecting the pathway contributing to intimal hyperplasia. An important
      component of this pathway involves matrix metalloproteinases (MMPs), implicated
      in vascular remodeling due to their ability to degrade components of the
      extracellular matrix. We hypothesize that estrogen (Est) and progesterone (Prog)
      upregulate the MMP pathway in vascular smooth muscle cells (VSMCs) thereby
      increasing MMP activity and function. METHODS AND RESULTS: VSMCs were incubated
      with Est (5 ng/mL), Prog (50 ng/mL), Est + Prog combination (Est/Prog), and/or
      doxycycline (40 microg/mL; Doxy). Using reverse transcriptase polymerase chain
      reaction (RT-PCR) analysis we have previously shown membrane type 1-MMP (MT1-MMP)
      messenger ribonucleic acid (mRNA) levels are significantly increased by Est.
      Here, Western blot analyses indicated MT1-MMP and MMP-2 protein levels, not
      tissue inhibitor of MMP-2 (TIMP-2), were increased in response to Est and
      Est/Prog (P < .05 vs control). In-gel zymography revealed that Est and Est/Prog
      resulted in increased MMP-2 activity (hormone groups, P < .05 vs control) with no
      significant difference among the hormone groups. VSMC migration was increased by
      45 +/- 14% in response to Est (P < .05 vs control), as measured using a modified
      Boyden chamber assay. Doxycycline significantly inhibited basal and Est/Prog
      stimulated increases in MMP-2 activity (P < .05 vs control; P < .05 vs hormone
      groups), and partially blocked basal and hormonally stimulated migration (P < .05
      vs control and Est). CONCLUSION: Estrogen and progesterone affects the MMP
      pathway by increasing MMP-2 enzymatic activity, possibly via the upregulation of
      MT1-MMP expression without a corresponding increase in TIMP expression. This
      increased collagenase activity increases VSMC motility and their ability to
      migrate through a collagen type IV lattice. Est/Prog upregulation of MT1-MMP may
      contribute to the adverse effect of HRT on vascular interventions.

PMID- 18829230
TI  - Reimbursement of long-term postplacement costs after endovascular abdominal
      aortic aneurysm repair.
AB  - OBJECTIVE: Postplacement cost of surveillance and secondary procedures over 5
      years increases the global cost of endovascular aortic aneurysm repair (EVAR) by
      nearly 50%. This study identified and assessed the reimbursement received for
      long-term postplacement costs after EVAR. METHODS: Between December 1995 and June
      2007, 360 patients underwent EVAR at a single institution. The reimbursement
      collected from charges of postplacement surveillance and secondary procedures
      related to the aneurysmal disease was evaluated and compared against the actual
      costs. All amounts were converted to year 2007 dollars. To minimize costs
      associated with the early learning curve, the initial 50 EVAR patients between
      December 1995 and 1998 were excluded. Patients with <1 year follow-up were also
      excluded. Data are expressed as mean +/- standard error. RESULTS: The mean follow
      up after EVAR for 152 patients was 38.8 +/- 1.8 months. Medicare, capitated
      insurance, and commercial insurance provided coverage for 85 (56.0%), 49 (32.2%),
      and 18 (11.8%) patients, respectively. The cumulative 5-year postplacement
      reimbursement received per patient was $9792 meeting 81.4% of the cumulative cost
      of $12,027 for a net loss of $2235 per patient. Although 123 (80.9%) patients
      without secondary procedures generated a 5-year cumulative gain of $1830 per
      patient, 29 (19.1%) patients with secondary procedures averaged a 5-year
      cumulative loss of $9378 per patient. The average reimbursement rate over the 5
      year period was 35.8% +/- 0.6%, with the lowest reimbursement rate seen in
      patients with Medicare at 31.6% +/- 0.7%. CONCLUSION: Current reimbursement is
      not sufficient to meet the costs associated with long-term surveillance and
      needed secondary procedures after EVAR. Inadequate reimbursement of costs
      associated with secondary procedures was the primary driver for the net
      institutional loss. Reimbursement for outpatient radiological procedures
      generated a modest surplus.

PMID- 18829231
TI  - Validation of a method for determination of the ankle-brachial index in the
      seated position.
AB  - OBJECTIVE: To validate a method for determination of the ankle-brachial index
      (ABI) in the seated position. BACKGROUND: Peripheral arterial disease (PAD) is a
      prevalent disorder that is associated with quality of life impairment and
      increased risk of a major cardiovascular event. The ABI is the initial test for
      screening and diagnosis of PAD. To prevent error due hydrostatic pressure,
      accurate measurement of the ABI requires supine patient positioning. Access to
      ABI measurement is limited for patients who are immobilized or unable to lie
      flat. METHODS: Patients presenting to a vascular laboratory for suspected
      arterial disease were enrolled. Arm and ankle blood pressures were measured in
      the supine and seated positions. Seated ankle pressures were corrected by the
      following physiology-based formula: Corrected ankle pressure = Measured ankle
      pressure - D*(.078), where D = the vertical distance between the arm and ankle
      cuffs (mm). This formula equates to a correction factor of 78 mm Hg per meter
      distance between the arm and ankle cuffs. Corrected ankle pressure measurements
      were used for seated ABI calculation. RESULTS: Complete data were available for
      100 patients. Mean ABI was 0.97, and 31% of patients had an ABI < or =0.9. There
      was excellent correlation between supine and corrected seated ankle pressure
      measurements (r = 0.884-0.936, P < .001). The difference between measurements was
      negligible (<5 mm Hg). Similarly, there was excellent correlation between supine
      and seated ABI measures (r = 0.936, P < .001). There was no significant
      difference between the supine and seated ABI measures. CONCLUSION: We have
      developed and validated a method for determination of the ABI in the seated
      position which can be used to broaden availability of PAD testing. This method
      could also be incorporated into new technologies for ABI determination in the
      seated position.

PMID- 18829232
TI  - Analysis of motor and somatosensory evoked potentials during thoracic and
      thoracoabdominal aortic aneurysm repair.
AB  - OBJECTIVES: Use of motor evoked potentials (MEP) and somatosensory evoked
      potentials (SSEP) monitoring during thoracic and thoracoabdominal aortic surgery
      is controversial. This study evaluated the intraoperative use of SSEP and MEP
      during thoracoabdominal repair and assessed their role in decreasing the risk of
      spinal cord ischemia and paralysis. METHODS: We conducted paired SSEP and MEP
      monitoring to assess agreement between the methods and their ability to predict
      neurologic outcome in 233 patients. Changes in SSEP and MEP monitoring were
      classified as no change, reversible change, or irreversible change during the
      intraoperative period and by the conclusion of surgery. Agreement between the
      methods was computed using the Cohen kappa statistic. Sensitivity, specificity,
      and positive and negative predictive values were computed for each method on the
      immediate and delayed neurologic deficit. RESULTS: Immediate neurologic deficit,
      determined immediately upon awakening from anesthesia and confirmed by a
      neurologist, occurred in eight of 233 (3.4%) patients. For any change (reversible
      plus irreversible), agreement between MEP and SSEP was relatively low (kappa =
      0.53), despite being highly statistically significant (P < .001). MEP tended to
      overestimate SSEP for immediate neurologic deficit, demonstrating a 53% false
      positive rate, compared with a 33% false-positive rate for SSEP (specificity
      ratio, 1.42; P < .0001). With irreversible change, agreement between the methods
      was 90% (kappa = 0.896, P < .0001). Only irreversible change was significantly
      associated with neurologic outcome (odds ratio, 21.9; P < .00001 for SSEP; 60.8,
      P < .0001 for MEP), but sensitivity and positive predictive values were low (37%
      and 33% for SSEP; 22% and 45% for MEP, respectively). Reversible changes in
      neurophysiologic monitoring were not significantly associated with immediate
      neurologic deficit. Negative predictive values for all negative evoked potential
      findings were >98% for immediate deficit. No evoked potential variables were
      associated with delayed deficit. CONCLUSIONS: SSEP and MEP monitoring were highly
      correlated only when intraoperative changes were irreversible. Reversible changes
      were not significantly associated with immediate neurologic deficit. Irreversible
      changes were significantly associated with immediate neurologic deficit, and the
      findings were identical for SSEP and MEP in this variable, indicating that the
      more complex MEP measures do not add further information to that obtained from
      SSEP. Normal SSEP and MEP findings had a strong negative predictive value,
      indicating that patients without signal loss are unlikely to awake with
      neurologic deficit.

PMID- 18829233
TI  - Infrainguinal cutting balloon angioplasty in de novo arterial lesions.
AB  - BACKGROUND: This prospective, non-randomized study evaluated the short- and mid
      term feasibility, safety, primary patency, and limb salvage of cutting balloon
      percutaneous transluminal angioplasty (CB-PTA) for the treatment of peripheral
      arterial occlusive disease (PAOD). METHODS AND RESULTS: All data were collected
      for 128 consecutive patients who underwent CB-PTA to improve infrainguinal
      arterial circulation between January 2003 and July 2007. One-hundred thirty-five
      limbs with PAOD (claudication, n = 19; critical limb ischemia [CLI], n = 116)
      were treated. Patency was evaluated by clinical examination and duplex
      ultrasonography. A total of 203 lesions (183 stenoses, 20 occlusions) were
      treated in 66 femoropopliteal and 69 infrapopliteal arterial segments. The
      TransAtlantic Inter-Societal Consensus (TASC) classification of the primary
      lesions was A in 41.5%, B in 45.2%, C in 8.2%, and D 5.1%. Mean follow-up was
      16.1 +/- 9.7 months. The overall technical success rate was 96.3% and the
      complication rate was 8.9%. There were two (1.5%) perioperative deaths. The
      primary patency rate was 82.1% at 12- and 24-months in patients with claudication
      (femoropopliteal lesions). The 1- and 2-year results for femoropopliteal and
      infrapopliteal lesions in patients with CLI were: primary patency 64.4% and 51.9
      %, respectively; limb salvage 84.2% and 76.9%; survival 92.6% and 88.5%. More
      distal lesions and TASC classification were significant independent risk factors
      for outcome (P < .05). Treatment of multiple segment lesions was an independent
      predictor of a favorable outcome (P = .04). CONCLUSION: CB-PTA is safe and
      feasible for the treatment of infrainguinal arterial occlusive disease, with
      relatively low mid-term restenosis rates compared to other endovascular
      treatments. However, these data cannot be extrapolated to potential outcomes for
      lesions >10 cm in length. Further follow-up will be necessary to evaluate the
      long-term results of CB-PTA.

PMID- 18829234
TI  - Leptin receptor is elevated in carotid plaques from neurologically symptomatic
      patients and positively correlated with augmented macrophage density.
AB  - BACKGROUND: Carotid artery lesions from symptomatic patients are characterized by
      inflammation and neovascularization. The adipokine leptin promotes angiogenesis
      and activates inflammatory cells, and the leptin receptor (ob gene-encoded
      receptor), ObR, is expressed in advanced atherosclerotic lesions. The present
      study quantitatively analyzed ObR messenger RNA (mRNA) expression and
      immunoreactivity in carotid artery plaques from symptomatic and asymptomatic
      persons. Plaque angiogenesis, gene expression of vascular endothelial growth
      factor (VEGF), and macrophage density were also analyzed. METHODS: Carotid
      endarterectomy specimens were collected from 26 patients undergoing surgery for
      hemispheric cerebrovascular symptoms (n = 13) or progressive asymptomatic
      internal carotid stenosis (n = 13). A representative sample, including part of
      the most active site, was collected from each lesion and evaluated by real-time
      polymerase chain reaction analysis for ObR(long) and ObR(common) isoforms,
      VEGF(165), and macrophage adhesion molecule-1 (Mac-1) mRNA, and by
      immunohistochemistry for ObR, von Willebrand factor (vWF), and CD68 antigen
      expression. RESULTS: All plaques exhibited advanced atherosclerosis (American
      Heart Association class IV through VI). Transcript levels were preferentially
      elevated in symptomatic plaques for ObR(long) (P = .0006) and ObR(common) (P =
      .033), with a simultaneous upregulation of VEGF(165) (P = .001) and Mac-1 mRNA
      expression (P = .003). Immunohistochemical analysis confirmed a significant
      increase of ObR antigen levels (P = .011) and CD68-positive inflammatory cells (P
      = .049) in symptomatic plaques, whereas neovascularization, evident in all
      plaques, was similar in both groups (P = .7). CONCLUSION: The ObR(long) and
      ObR(common) genes are upregulated and their protein preferentially synthesized in
      clinically symptomatic carotid plaques. Moreover, ObR expression is positively
      correlated with augmentation of gene transcripts related to macrophage density
      and neovascularization. These data suggest that ObR(long) and ObR(common) may be
      linked with histologic features of carotid plaque instability, which are
      associated with cerebral ischemic symptoms.

PMID- 18829235
TI  - Early and midterm results after endovascular stent graft repair of penetrating
      aortic ulcers.
AB  - PURPOSE: To present early and midterm results after endovascular stent graft
      repair of patients with penetrating aortic ulcers (PAU). METHODS: Between January
      1997 and March 2008, a total of 202 patients received thoracic aortic
      endografting in our institution, 48 patients (32 men, median age 70 years, range,
      48-89) with PAU. A retrospective analysis of these patients was performed. Thirty
      one patients (65%) showed an acute aortic syndrome (8 contained rupture, 23
      symptomatic). Follow-up scheme included postoperative computed tomography
      angiography prior to discharge, at 3, 6, and 12 months, and yearly thereafter.
      Mean follow-up was 31.3 months (1.3-112.6). RESULTS: Technical success was
      achieved in 93.7%. Primary clinical success rate was 81.2%. In-hospital mortality
      was 14.6%. Perioperative mortality was significantly (P = .036) higher in
      patients with acute aortic syndrome compared to asymptomatic patients (22.5% vs
      0%). Postoperative complications occurred in 15 patients (31%), including 2
      patients with minor strokes and 6, respectively, 5 patients with cardiac and/or
      respiratory complications. Early endoleaks were observed in 9 patients (19%),
      late endoleaks in another 2 patients. Reintervention was necessary in 4 out of 48
      patients (8.4%). The actuarial survival estimates at 1, 3, and 5 years were 78%
      +/- 6%, 74% +/- 7%, and 61% +/- 10%, respectively. There was no aortic-related
      death during follow-up. Cox regression showed age (hazard ratio [HR]; 1.08, P =
      .036) and a maximum aortic diameter >50 mm (HR, 4.92; P = .021) as independent
      predictors of death. CONCLUSION: Endovascular treatment of penetrating aortic
      ulcers is associated with a relevant morbidity and mortality rate in frequently
      highly comorbid patients. Midterm results could prove a sustained treatment
      success regarding actuarial survival and aortic-related death. Emergencies show a
      significantly worse outcome, but treatment is still warranted in these
      symptomatic patients.

PMID- 18829236
TI  - Carotid artery stenting has increased rates of postprocedure stroke, death, and
      resource utilization than does carotid endarterectomy in the United States, 2005.
AB  - OBJECTIVE: Carotid endarterectomy (CEA) remains the procedure of choice for
      treatment of patients with severe carotid artery stenosis. The role of carotid
      artery stenting (CAS) in this patient group is still being defined. Prior single
      and multicenter studies have demonstrated economic savings associated with CEA
      compared with CAS. The purpose of this study was to compare surgical outcomes and
      resource utilization associated with these two procedures at the national level
      in 2005, the first year in which a specific ICD-9 procedure code for CAS was
      available. METHODS: All patient discharges for carotid revascularization for the
      year 2005 were identified in the Nationwide Inpatient Sample based on ICD9-CM
      procedure codes for CEA (38.12) and CAS (00.63). The primary outcome measures of
      interest were in-hospital mortality and postoperative stroke; secondary outcome
      measures included total hospital charges and length of stay (LOS). All
      statistical analyses were performed using SAS version 9.1 (Cary, NC), and data
      are weighted according to the Nationwide Inpatient Sample (NIS) design to draw
      national estimates. Univariate analyses of categorical variables were performed
      using Rao-Scott chi(2), and continuous variables were analyzed by survey weighted
      analysis of variance (ANOVA). Multivariate logistic regression was performed to
      evaluate independent predictors of postoperative stroke and mortality. RESULTS:
      During 2005, an estimated 135,701 patients underwent either CEA or CAS
      nationally. Overall, 91% of patients underwent CEA. The mean age overall was 71
      years. Postoperative stroke rates were increased for CAS compared with CEA (1.8%
      vs 1.1%, P < .05), odds ratio (OR) 1.7; (95% confidence interval [CI] 1.2-2.3).
      Overall, mortality rates were higher for CAS compared with CEA (1.1% vs 0.57%, P
      < .05) this difference was substantially increased in regard to patients with
      symptomatic disease (4.6% vs 1.4%, P < .05). By logistic regression, CAS trended
      toward increased mortality, OR 1.5; (95% CI .96-2.5). Overall, the median total
      hospital charges for patients that underwent CAS were significantly greater than
      those that underwent CEA ($30,396 vs $17,658 P < .05). CONCLUSIONS: Based on a
      large representative sample during the year 2005, CEA was performed with
      significantly lower in-hospital mortality, postoperative stroke rates, and lower
      median total hospital charges than CAS in US hospitals. As the role for CAS
      becomes defined for the management of patients with carotid artery stenosis,
      clinical as well as economic outcomes must be continually evaluated.

PMID- 18829237
TI  - Duplex ultrasound in aneurysm surveillance following endovascular aneurysm
      repair: a comparison with computed tomography aortography.
AB  - OBJECTIVES: Cumulative radiation dose, cost, and increased demand for computed
      tomography aortography (CTA) suggest that duplex ultrasonography (DU) may be an
      alternative to CTA-based surveillance. We compared CTA with DU during
      endovascular aneurysm repair (EVAR) follow-up. METHODS: Patients undergoing EVAR
      had clinical and radiological follow-up data entered in a prospectively
      maintained database. For the purpose of this study, the gold standard test for
      endoleak detection was CTA, and an endoleak detected on DU alone was assumed to
      be a false positive result. DU interpretation was performed independently of CTA
      and vice versa. RESULTS: One hundred thirty-two patients underwent EVAR, of whom
      117 attended for follow-up ranging from six months to nine years (mean, 32
      months). Adequate aneurysm sac visualisation on DU was not possible in 1.7% of
      patients, predominantly due to obesity. Twenty-eight endoleaks were detected in
      28 patients during follow-up. Of these, 24 were initially identified on DU (four
      false negative DU examinations), and eight had at least one negative CTA with a
      positive DU prior to diagnosis. Twenty-three endoleaks were type II in nature and
      three of these patients had increased sac size. There was one type I and four
      type III endoleaks. Two of these (both type III) had an increased sac size. Of 12
      patients with increased aneurysm size of 5 mm or more at follow-up, five had an
      endoleak visible on DU, yet negative CTA and a further five had endoleak
      visualisation on both DU and CTA. Of six endoleaks which underwent re
      intervention, all were initially picked up on DU. One of these endoleaks was
      never demonstrated on CTA and a further two had at least one negative CTA prior
      to endoleak confirmation. Positive predictive value for DU was 45% and negative
      predictive value 94%. Specificity of DU for endoleak detection was 67% when
      compared with CTA, because of the large number of false positive DU results.
      Sensitivity for DU was 86%, with all clinically significant endoleaks
      demonstrated on CTA also detected on DU. CONCLUSION: Despite its low positive
      predictive value, we found DU to be a sensitive test for the detection of
      clinically significant endoleaks. Given concerns about cumulative radiation
      exposure and cost, and the surprisingly low sensitivity of CTA for endoleak
      detection in this series, selective CTA based on DU surveillance may be a more
      appropriate long-term strategy.

PMID- 18829238
TI  - Efficacy of protected renal artery primary stenting in the solitary functioning
      kidney.
AB  - BACKGROUND: Significant renal artery stenosis (RAS) in a solitary functioning
      kidney (SFK) represents one of the most acceptable indications for renal
      revascularization. Percutaneous transluminal renal artery stenting (PTRAS) is
      increasingly being used as a first line treatment for renal revascularization,
      associated with renal function improvement or stabilization in the majority of
      the patients with solitary kidneys, but also with deterioration in up to 38% of
      the cases. Atheroembolism during PTRAS has been postulated as a potential cause
      for this acute renal function worsening. The aim of this study was to report on
      the feasibility, safety, and early outcomes of PTRAS in a series of patients with
      SFK using distal embolic protection (DEP). METHODS: All PTRAS procedures in SFKs
      performed under DEP between June 2002 and September 2007 were reviewed. Renal
      function, blood pressure, and the number of anti-hypertensive medications were
      assessed pre- and post-intervention. Renal function improvement and deterioration
      were defined as a 20% increase and decrease in serum creatinine, respectively,
      compared with preoperative values. Primary and primary assisted patency rates
      were also calculated. Statistical differences between values before and after
      intervention were determined by the Student t test and statistical significance
      was taken at P < .05. RESULTS: Protected PTRAS was performed in 14 patients with
      a SFK (9 men, 6 women, mean age 65.6 +/- 6.8 years). All patients were
      hypertensive and had varying degrees of azotemia. Mean pre-intervention stenosis
      degree was 86.8% +/- 7.8%. Immediate technical success was obtained in 100% of
      the patients. Renal function was cured (7.1%), improved (50%), or stabilized
      (42.9%) in all 14 (100%) patients after the procedure and no deterioration was
      noticed in any patient at 6-month follow-up. Pre- and postintervention serum
      creatinine levels were 3.01 +/- 1.15 mg/dL and 2.16 +/- 0.68 mg/dL, respectively,
      (P = .02). Hypertension was improved in 6 (42.9%) patients and stabilized in the
      remaining 8 (57.1%). Primary patency was 100% and 90% at 1 and 3 years,
      respectively, while primary assisted patency remained 100% for the whole follow
      up period (mean, 31.8 +/- 19.4 months). CONCLUSION: These findings suggest that
      in patients with a SFK, protected PTRAS represents a safe and effective treatment
      for halting the progression of renal dysfunction to renal loss and warrants
      further investigation.

PMID- 18829239
TI  - Outcomes of endovascular abdominal aortic aneurysm repair compared with open
      surgical repair in high-risk patients: results from the Swedish Vascular
      Registry.
AB  - BACKGROUND: The management of infrarenal aortic aneurysms in high-risk patients
      remains a challenge. Endovascular aneurysm repair (EVAR) is associated with
      superior short-term mortality rates but unclear long-term results and has not
      been shown to improve survival in patients unfit for open repair (OR). The aim of
      this population-based study was to evaluate the outcome after elective EVAR
      compared with OR in a high-risk patient cohort. METHODS: Prospectively collected
      data from January 2000 to December 2006 were retrieved from the Swedish Vascular
      Registry. The high-risk cohort was defined as age >or=60 years, American
      Anesthesiologists Association (ASA) class 3 or 4, and at least one cardiac,
      pulmonary, or renal comorbidity. These criteria were met by 217 of 1000 EVAR
      patients and 483 of 2831 OR patients. Primary end points were 30-day and 1-year
      all-cause mortality. Kaplan-Meier curves for survival and multivariate Cox
      regression analyses were performed. RESULTS: The crude 30-day and 1-year all
      cause mortality rates for EVAR vs OR for the whole treatment group (n = 3831)
      were 1.8% vs 2.8% and 8.0% vs 7.2%, respectively. In the high-risk cohort (n =
      700), EVAR patients were approximately 2 years older and renal insufficiency and
      diabetes mellitus were more common, and smoking was more prevalent in the OR
      group. About two-thirds of EVAR procedures were performed at university hospitals
      and one-half of OR procedures were performed at county hospitals. In the high
      risk cohort, there was no difference in mortality at 30-days (EVAR, 4.6% vs OR,
      3.3%), but OR had lower 1-year mortality (8.5% vs 15.9%; P = .003). More bleeding
      complications occurred in the EVAR group, but more pulmonary complications
      occurred in the OR group; however, there was no difference in cardiac,
      cerebrovascular, or renal complications. The mean follow-up was 3.4 years. EVAR
      was associated with increased mortality risk after adjusting for age, ASA class,
      and comorbidities (hazard ratio, 1.50; 95% confidence interval, 1.07-2.12; P =
      .02). Kaplan-Meier survival analysis showed a lower mortality rate for patients
      undergoing OR, which remained during follow-up (P = .001). CONCLUSIONS: Elective
      OR of aortic aneurysms seems to have a better outcome compared with EVAR in this
      specific, population-based, high-risk patient cohort after adjusting for
      covariates. We cannot confirm the benefit of EVAR from previous registry studies
      with a similar high-risk definition. In clinical practice, OR may be at least as
      good as EVAR in high-risk patients fit for surgery.

PMID- 18829240
TI  - Angioplasty with stent graft versus bare stent for recurrent cephalic arch
      stenosis in autogenous arteriovenous access for hemodialysis: a prospective
      randomized clinical trial.
AB  - BACKGROUND: Early recurrent stenosis of the cephalic arch in autogenous
      arteriovenous access for hemodialysis is a common problem that requires stenting
      to prevent thrombosis. Because the results of stenting are unsatisfactory, we
      compared the efficacy of stent grafts with bare stents in these patients.
      METHODS: All patients who presented with recurrent cephalic arch stenosis >50%
      within 3 months of successful balloon angioplasty were randomized to have
      angioplasty and stenting with either a bare nitinol stent or a stent graft.
      Outcome was assessed by angiography 3 months later. Restenosis was defined as
      >50% narrowing of the stent lumen or of the vessel margin up to 0.5 cm adjacent
      to the stent. There were no exclusions. RESULTS: This report includes data on the
      outcome of 25 consecutive patients with recurrent cephalic arch stenosis who were
      treated from April to August 2006. At 3 months, three patients had died and one
      had undergone a renal transplant. The 21 patients who had angiography at 3 months
      had patent stents. Restenosis rates were seven of 10 (70%) in the bare stent
      group and two of 11 (18%) in the stent graft group (P = .024). Life-table
      analysis at 3 and 6 months showed that primary patency was 82% in the stent graft
      group and 39% in the bare stent group. One-year primary patency was 32% in the
      stent graft group and 0% in the bare stent group (P = .0023). During a mean
      follow-up of 13.7 months, nine patients died, four in the bare stent group and
      five in the stent graft group. Two patients in the stent graft group had received
      a renal transplant. The number of interventions per patient-year was 1.9 in the
      bare stent group and 0.9 in the stent graft group (P = .02). CONCLUSIONS: The use
      of stent grafts in angioplasty for recurrent cephalic arch stenosis significantly
      improved short-term restenosis rates and long-term patency compared with the use
      of bare stents. The significant improvement that emerged during the study caused
      accrual of patients to be halted for ethical reasons. This study altered our
      usage of stents for venous stenoses in arteriovenous accesses by eliminating bare
      nitinol stents in favor of stent grafts.

PMID- 18829241
TI  - Incidence of soft tissue injury and neuropathy after embolo/sclerotherapy for
      congenital vascular malformation.
AB  - PURPOSE: Embolo/sclerotherapy is an important treatment modality for vascular
      malformations, but the rates and results of the complications associated with
      embolo/sclerotherapy are not well known. We report the incidence and outcome of
      soft tissue injury and neuropathy after performing embolo/sclerotherapy for
      congenital vascular malformations (CVMs) classified according to the Hamburg
      classification. METHODS: Among 1823 patients with CVM, 573 were treated with
      embolo/sclerotherapy. We retrospectively reviewed 68 patients (31 males, 37
      females; mean age, 20.0 years) with soft tissue injury and 49 patients (16 males,
      33 females; mean age, 21.2 years) with neuropathy. The indications for
      embolo/sclerotherapy for CVM were that the CVMs affected the quality of life,
      such as a symptomatic or trauma-prone lesion or a lesion that was impairing the
      function of a limb, and the lesions that were located near a life-threatening
      vital area, including the airway. As embolo/sclerotherapy agents, absolute or 80%
      ethanol, N-butyl cyanoacrylate (NBCA), and various types of coils or contour
      particles were used in various combinations, either at the same time or in
      phases, depending on the location, severity, and extent of the CVM. RESULTS: The
      incidence of soft tissue injury was 29.4% (42 of 143) for the arteriovenous
      shunting type and 8% (22 of 273) for the venous type. No soft tissue injuries
      occurred in the patients with arterial and lymphatic malformations. Of the 68
      patients with soft tissue injury, 40 lesions healed with conservative management,
      and 28 lesions needed surgery, including escharectomy, skin graft, or amputation.
      The incidence of neuropathy was 10.9% (30 of 273) for the venous CVM. No
      neuropathy occurred in the patients with arterial malformations. Of the 49
      patients with neuropathy, 42 recovered at a mean period of 5.3 months, but seven
      did not. CONCLUSION: Soft tissue injuries occurred in 11.9% of patients (68 of
      573) and neuropathies occurred in 8.6% (49 of 573) after undergoing
      embolo/sclerotherapy. Most of these complications recovered by themselves (58.9%
      from soft tissue injury and 85.1% from neuropathy). Our results suggest that
      embolo/sclerotherapy has an acceptable incidence of soft tissue injury and
      neuropathy, when considering the effect that the CVM had on the quality of life
      before treatment, so embolo/sclerotherapy is recommended as a treatment modality
      for CVM.

PMID- 18829242
TI  - [Remote cerebellar hemorrhage].
AB  - Intracerebral hemorrhage remote from the site of surgery is an infrequent
      complication after neurosurgical procedures. Cerebellar hemorrhage after
      supratentorial craniotomy is the most commonly described pattern of remote
      hemorrhage unknown by the anesthesiologist. It is linked with a frequent
      morbidity and mortality. We report a case of this complication after meningioma
      surgery with a favorable outcome.

PMID- 18829243
TI  - [Tako-Tsubo syndrome after anaphylaxis caused by succinylcholine during general
      anaesthesia].
AB  - The Tako-Tsubo syndrome (or transient left ventricular apical balloning) is a new
      clinical entity, very similar to acute myocardial infarction, but different by
      its excellent short-term prognosis. It has been reported after a physical or an
      emotional stress, and it is diagnosed by a coronary angiogram and a left
      ventriculography. We report here a case of Tako-Tsubo syndrome related to an
      anaphylactic shock caused by succinylcholine during general anaesthesia of a
      female patient, wearing an unadjustable gastric band.

PMID- 18829244
TI  - [Ciguatera: recrudescence of symptomatology of a previous intoxication].

PMID- 18829245
TI  - [What is the best management in case of Rubigine ingestion?].

PMID- 18829246
TI  - [What are the consequences for the difficulties of leaving patients hospitalized
      in intensive care unit?].

PMID- 18829247
TI  - [Bone involvement during revealed late Gaucher's disease].

PMID- 18829248
TI  - [Pregnancy and antiphospholipid antibodies].
AB  - Antiphospholipid syndrome is one of the few treatable causes of pregnancy loss,
      and successful pregnancy rates of 70% or more can be achieved with appropriate
      treatment. Pregnancy in these women is associated with increased rates of
      preeclampsia, placental insufficiency, and preterm delivery. Several studies
      indicate that heparin, usually combined with low-dose aspirin, is beneficial in
      this indication. Recent works underlines the role of complement activation in a
      murine model of antiphospholipid pregnancy loss, which should be confirmed in
      Human.

PMID- 18829249
TI  - [Immunosuppressants for auto-immune diseases and pregnancy].
AB  - Therapeutic stability of a systemic disease is a priority during pregnancy. To
      stop an effective treatment, to reduce dosages or to switch to less effective
      treatments might induce some loss of chance for pregnant women, and eventually
      harmful consequences for fetuses. Due to the teratogenic effects of some
      immunosuppressants, childbearing susceptible women should use effective
      contraception and be informed of risks in case of pregnancy. A pre-conceptional
      consultation is of interest, allowing an adaptation of treatment and advices
      before pregnancy is ongoing. Mycophenolate is highly suspected to be teratogenic
      in humans. Mycophenolate should not be prescribed in women of childbearing
      potential unless some criteria are met. Maternal (even fetal) infectious
      conditions can occur during immunosuppressive treatments. Therefore,
      obstetricians and pediatricians should be aware of the maternal treatment in
      order to allow adequate monitoring of the mother and the neonate.

PMID- 18829250
TI  - [A neurological deficit multifocal pseudo infectious revealing a disseminated
      acute encephalomyelitis].

PMID- 18829251
TI  - [Bevacizumab-induced abdominal aortic thrombosis].

PMID- 18829252
TI  - [Prevention of chronic obstructive pulmonary disease exacerbations].
AB  - Exacerbations of chronic obstructive pulmonary disease (COPD) aggravate disease
      course, induce increased morbidity and mortality, impair quality of life, and
      raise the direct costs of COPD. Their prevention is essential and is an integral
      part of the COPD program defined by French health authorities for the 2005-2010
      period. Both pharmacologic and nonpharmacologic approaches have been shown to be
      effective in preventing exacerbations, but these treatments are still underused
      and misused. Important nonpharmacologic therapies that directly decrease the risk
      of exacerbation or hospitalization include smoking cessation, oxygen therapy,
      pulmonary rehabilitation, and education. Most of the drugs available for long
      term management of COPD have significant effects on the frequency of
      exacerbations: tiotropium and salmeterol, each used alone, as well as fixed
      combinations of salmeterol/fluticasone or formoterol/budesonide. Tiotropium
      reduces the frequency of exacerbation in both moderate and severe COPD. Inhaled
      glucocorticosteroid agents are not recommended alone. They must be prescribed
      only with a long-acting bronchodilator and only to patients with severe disease
      and repeated exacerbations. Influenza vaccination is recommended.

PMID- 18829253
TI  - A factor analytic comparison of five models of PTSD symptoms.
AB  - This study examined the factor structure of PTSD symptoms in a sample of college
      students (n=344) reporting exposure to a range of traumatic events. The sample
      was randomly split and an exploratory factor analysis was conducted with half of
      the sample. The factor structure obtained in the exploratory analysis was
      evaluated against three other models using confirmatory factor analysis utilizing
      the second half of the sample. This series of factor analyses identified and
      confirmed a three-factor symptom structure consisting of intrusion/avoidance,
      dysphoria, and hyperarousal clusters. These results add to the body of literature
      which has found that PTSD includes a cluster of symptoms shared with other
      diagnoses (dysphoria) and a more specific factor related directly to the effects
      of encountering traumatic experiences.

PMID- 18829254
TI  - Effects of personality disorder and other variables on professionals' evaluation
      of treatment features in individuals with mild intellectual disabilities and
      severe behavior problems.
AB  - The diagnosis personality disorder is often found among samples of adults with
      mild intellectual disability and severe behavioral and mental health disorders.
      The number of studies on the adverse effects of this diagnosis are scarce. Using
      vignets in the present study, we have explored the relationship between the
      diagnosis personality disorder and professionals' evaluation of treatment
      features. Professionals evaluate that in clients with this diagnosis treatment
      takes longer, a longstanding reduction in behavioral problems is less likely,
      focus of treatment is on adaptation of the context (instead of improving self
      control) and that the setting after clinical treatment will be more restrictive
      than in clients without this diagnosis. There is a significant interaction effect
      between the diagnosis personality disorder and the variable motivation for
      treatment. Both of these variables strongly and mutually influence professionals'
      evaluation of treatment features.

PMID- 18829255
TI  - Robust support vector regression in the primal.
AB  - The classical support vector regressions (SVRs) are constructed based on convex
      loss functions. Since non-convex loss functions to a certain extent own
      superiority to convex ones in generalization performance and robustness, we
      propose a non-convex loss function for SVR, and then the concave-convex procedure
      is utilized to transform the non-convex optimization to convex one. In the
      following, a Newton-type optimization algorithm is developed to solve the
      proposed robust SVR in the primal, which can not only retain the sparseness of
      SVR but also oppress outliers in the training examples. The effectiveness, namely
      better generalization, is validated through experiments on synthetic and real
      world benchmark data sets.

PMID- 18829256
TI  - Solitary fibrous tumor of the tongue: case report and literature review.
AB  - Solitary fibrous tumor (SFT) is an uncommon spindle cell neoplasm with
      unpredictable behavior. It was originally described in the pleura, but is now
      known to occur in various locations. SFT of the tongue is rare, with only four
      cases on record. An SFT of the anterolateral part of the left side of the tongue,
      which occurred in a 48 year-old man is recorded. The tumor was resected and the
      patient remains free of recurrence 3 years postoperatively.

PMID- 18829258
TI  - Vulnerability of the frontal-temporal connections in temporal lobe epilepsy.
AB  - OBJECTIVE: In temporal lobe epilepsy (TLE), frontal-temporal connections are
      integral parts of the epileptogenic network. Although frontal-temporal gray
      matter abnormalities have been consistently demonstrated in TLE, white matter
      connections between these two lobes require further study in this disease
      setting. We therefore investigated the integrity of two major frontal-temporal
      white matter association tracts, uncinate fasciculus (UF) and arcuate fasciculus
      (AF), and their clinical correlates. METHODS: Using diffusion tensor imaging
      (DTI) tractography, integrity of the UF and AF was examined in 22 individuals (12
      subjects with TLE and 10 age-matched healthy controls). DTI indices of these
      tracts were compared between the two subject groups and correlates examined with
      clinical variables that included age of seizure onset, duration of epilepsy,
      history of febrile seizure and antiepileptic medication exposure. RESULTS: In
      subjects with TLE, the fractional anisotropy (FA) and apparent diffusion
      coefficient (ADC) of UF and AF ipsilateral to the side of seizure onset were
      abnormal when compared to healthy controls. Furthermore, lower UF FA correlated
      with earlier age of seizure onset. CONCLUSION: TLE is associated with abnormal
      integrity of frontal-temporal white matter tracts, but only on the side of
      seizure onset. This suggests that frontal-temporal white matter tracts are
      vulnerable to recurrent seizures and/or the factors precipitating the epilepsy.

PMID- 18829259
TI  - Levetiracetam in newly diagnosed late-onset post-stroke seizures: a prospective
      observational study.
AB  - Levetiracetam (LEV) monotherapy was investigated in 35 patients (pts) (16M/19F,
      71.9+/-7.3 years of age) with late-onset post-stroke seizures (i.e. seizures
      occurring at least 2 weeks after an ischemic stroke) in a prospective open-label
      study. Overall, 27 pts (77.1%) achieved a condition of seizure freedom (defined
      as 1 year without seizures): 19 (54.3%) at a daily LEV dose of 1000mg, 7 (20.0%)
      at 1500mg, 1 (2.8%) at 2000mg. Four pts (11.4%) discontinued the drug because of
      intolerable side effects (drowsiness associated to gait disturbance in 1 pt, and
      aggressive behaviour in the remaining 3 pts); 3 pts were unresponsive at a dose
      of 3000mg, and 1 pt was lost at follow-up. These observations suggest that LEV
      exhibits safety and efficacy profiles which make it an optimal candidate as a
      first-choice drug against post-stroke seizures.

PMID- 18829260
TI  - Outcome after discharge from an early psychosis program.
AB  - Studies defining the course and outcome of individuals experiencing their first
      episode (FE) of psychosis generally report an improvement in symptoms and
      functioning. Today, many FE patients are treated in specialized early psychosis
      programs. Little is known what happens to these individuals after discharge from
      these programs back to regular services. We report here on the outcomes of the
      first 200 subjects admitted to a three year specialized first episode service who
      could be contacted for assessments between 1 and 2 years after discharge.
      Approximately 50% of those initially assessed in a first episode service were
      able to be followed for up to 5 years. Results were that, although there was no
      further improvement in positive symptoms, there was continued improvement in
      social functioning and signs of improvement in negative symptoms.

PMID- 18829261
TI  - TDP-43 is not present in brain tissue of patients with schizophrenia.

PMID- 18829262
TI  - Reduced interhemispheric connectivity in schizophrenia-tractography based
      segmentation of the corpus callosum.
AB  - BACKGROUND: A reduction in interhemispheric connectivity is thought to contribute
      to the etiology of schizophrenia. Diffusion Tensor Imaging (DTI) measures the
      diffusion of water and can be used to describe the integrity of the corpus
      callosum white matter tracts, thereby providing information concerning possible
      interhemispheric connectivity abnormalities. Previous DTI studies in
      schizophrenia are inconsistent in reporting decreased Fractional Anisotropy (FA),
      a measure of anisotropic diffusion, within different portions of the corpus
      callosum. Moreover, none of these studies has investigated corpus callosum
      systematically, using anatomical subdivisions. METHODS: DTI and structural MRI
      scans were obtained from 32 chronic schizophrenic subjects and 42 controls.
      Corpus callosum cross sectional area and its probabilistic subdivisions were
      determined automatically from structural MRI scans using a model based deformable
      contour segmentation. These subdivisions employ a previously generated
      probabilistic subdivision atlas, based on fiber tractography and anatomical lobe
      subdivision. The structural scan was then co-registered with the DTI scan and the
      anatomical corpus callosum subdivisions were propagated to the associated FA map.
      RESULTS: Results revealed decreased FA within parts of the corpus interconnecting
      frontal regions in schizophrenia compared with controls, but no significant
      changes for callosal fibers interconnecting parietal and temporo-occipital brain
      regions. In addition, integrity of the anterior corpus was statistically
      significantly correlated with negative as well as positive symptoms, while
      posterior measures correlated with positive symptoms only. CONCLUSIONS: This
      study provides quantitative evidence for a reduction of interhemispheric brain
      connectivity in schizophrenia, involving corpus callosum, and further points to
      frontal connections as possibly disrupted in schizophrenia.

PMID- 18829263
TI  - Telomerase levels in schizophrenia: a preliminary study.
AB  - We previously demonstrated that telomere length was markedly reduced in
      peripheral blood lymphocytes from individuals with schizophrenia. Since reduced
      telomere length can be caused by decreased telomerase activity, we quantitated
      basal telomerase activity in peripheral blood lymphocytes derived from
      individuals with schizophrenia (n=53), unaffected relatives (n=31) and unrelated
      controls (n=59). Telomerase activity varied greatly among individuals, suggesting
      that this enzymatic activity is affected by various factors. We observed a
      nominally significant decrease in telomerase activity among individuals with
      schizophrenia compared to unaffected individuals (unaffected relatives and
      unrelated controls). Further studies are needed to investigate the role of
      telomerase in schizophrenia.

PMID- 18829264
TI  - Preferential semantic fluency impairment is related to hallucinations, but not
      formal thought disorder.
AB  - Semantic memory dysfunction in schizophrenia spectrum disorders has been
      theoretically linked primarily to formal thought disorder (FTD) and, to a lesser
      extent, hallucinations. Although past studies have demonstrated associations
      between FTD and semantic memory dysfunction, the potential influence of
      hallucinations and other symptoms on this association has not previously been
      evaluated. We investigated the relationship between semantic dysfunction and
      levels of schizophrenic symptoms in 75 patients with a DSM-IV diagnosis of
      schizophrenia/schizoaffective disorder. Symptoms were rated on a 0-5 scale using
      the Scale for Assessment of Positive Symptoms/Scale for Assessment of Negative
      Symptoms. Semantic dysfunction was quantified through a semantic/phonological
      fluency difference score. The vocabulary test from the Shipley Institute of
      Living Scale was included as a measure of pre-morbid IQ. We hypothesized a
      relationship between FTD and semantic dysfunction, with an alternative hypothesis
      being that semantic dysfunction would be related to hallucinations. The measure
      of semantic dysfunction was significantly correlated with level of hallucinations
      (r=-.35, p=.002), but not level of FTD (r=.05, p=.67). The relationship between
      hallucinations and semantic dysfunction remained significant after control for
      age and verbal intellectual ability, and after controlling for the influence of
      other symptoms. This finding supports theories linking a breakdown in semantic
      associative networks to the production of hallucinations, and suggests that past
      associations between formal thought disorder and semantic dysfunction may have
      been at least partly driven by differential levels of hallucinations between
      groups.

PMID- 18829265
TI  - Antiwrinkle effect of adipose-derived stem cell: activation of dermal fibroblast
      by secretory factors.
AB  - BACKGROUND: Adipose-derived stem cells (ADSC) have wound-healing and antioxidant
      effects on human skin via secretion of growth factors and activation of dermal
      fibroblasts. OBJECTIVE: Paracrine mechanism reducing ultraviolet-B (UVB)-induced
      wrinkles by ADSC is investigated in this study. METHODS AND RESULTS: Wrinkles
      were induced by an eight-week UVB irradiation, and were significantly improved by
      the subcutaneous injection of ADSC in hairless mice. In a replica analysis,
      parameters involving wrinkles were improved with mid-level and high doses of ADSC
      (1x10(4) and 1x10(5) cells). Dermal thickness and collagen contents in the dermis
      also were increased in the ADSC-injected groups. To characterize the paracrine
      mechanism involving the antiwrinkle effect of ADSC, a conditioned medium of ADSC
      (ADSC-CM) was directly incubated in human dermal fibroblasts (HDF). UVB
      irradiation reduced the proliferation of HDF, but this was reversed by the
      pretreatment of ADSC-CM in a dose-dependent manner. In a cell cycle analysis,
      ADSC-CM decreased the UVB-induced apoptotic cell death, which was demonstrated by
      the reduced sub-G1 phase of HDF. In addition, the ADSC-CM increased the protein
      expression of collagen type I and decreased the protein level of matrix
      metalloproteinase 1 in HDF, which may account for the increased collagen contents
      in the dermis. CONCLUSIONS: Collectively, these results indicate that the ADSC
      and its secretory factors are effective for UVB-induced wrinkles, and the
      antiwrinkle effect is mainly mediated by reducing UVB-induced apoptosis and
      stimulating collagen synthesis of HDF.

PMID- 18829266
TI  - Adjuvant effect of lipopolysaccharide on the induction of contact
      hypersensitivity to haptens in mice.
AB  - BACKGROUND: Toll-like receptor (TLR) 4 is a critical receptor and signal
      transducer for lipopolysaccharide (LPS), a major component of Gram-negative
      bacteria. The MyD88-independent pathway downstream of TLR4 leads to functional
      dendritic cell (DC) maturation, although LPS-induced cytokine production from DCs
      is MyD88-dependent. OBJECTIVES: We investigated whether intracutaneously injected
      LPS alters the functions of cutaneous DCs, leading to enhanced contact
      hypersensitivity (CH). METHODS: The ear swelling response was measured to
      evaluate the magnitude of CH. Cell proliferation of allogeneic splenocytes
      stimulated by DC-enriched draining lymph node (LN) cells was measured by
      performing a [(3)H]-thymidine incorporation assay. Epidermal I-A+ cells were
      evaluated under an epifluorescent microscope. I-A+ FITC-bearing cells from the
      draining LNs 24h after FITC application were analyzed on FACScan. RESULTS: LPS
      augmented CH induction in C3H/HeN (HeN) and MyD88-knockout (KO) mice but not in
      C3H/HeJ (HeJ) and H-2S(d)-bearing strains such as BALB/c mice. LPS failed to
      augment the allo-stimulatory ability of DCs in the draining LNs after hapten
      applications. LPS altered the density and morphology of epidermal I-A+ cell in
      HeN and BALB/c mice but not in TLR4-deficient HeJ mice. LPS increased the
      proportion of I-A+ FITC-bearing cells in the LNs 24h after FITC application in
      HeN, but not in BALB/c and HeJ. CONCLUSIONS: LPS augments the ability of DCs to
      migrate to the draining LNs, leading to enhanced CH via a TLR4-dependent, MyD88
      independent pathway. The different effects of LPS on CH in some strains of mice
      may explain individual differences in the susceptibility to establish CH to daily
      antigen exposures in clinical settings.

PMID- 18829267
TI  - Monitoring efficacy of cryotherapy for superficial basal cell carcinomas with in
      vivo reflectance confocal microscopy: a preliminary study.
AB  - BACKGROUND: Superficial BCCs (sBCCs) usually appear as multiple lesions in
      chronic sun-damaged skin of elderly people and may show a destructive growth if
      left untreated. Non-invasive treatment modalities, such as cryotherapy have been
      employed for sBCCs, all failing to provide tissue for confirming diagnosis and
      assessing adequacy of tumour removal. Reflectance confocal microscopy (RCM), a
      new non-invasive imaging technique has proven to be a useful tool for detection
      of basal cell carcinoma in vivo. OBJECTIVE: To non-invasively assess efficacy of
      cryotherapy for sBCCs by cytomorphologic analysis using RCM. METHODS: We examined
      10 histologically proven sBCCs located on the trunk of 5 consecutive patients
      with a mean age of 84.6 years. SBCCs were frozen twice using a spray nitrogen
      cryoprobe. RCM imaging was performed in each sBCC before cryotherapy and after 5
      and 24h to monitor resulting tissue injury. Distinct cytomorphologic
      characteristics were determined by three observers allowing non-invasive
      evaluation of therapeutic efficacy of treatment immediately after cryotherapy.
      Tumour clearance was assessed by RCM imaging 3 months after therapy followed by
      histopathologic examination. RESULTS: Characteristic RCM-features of BCC were
      present in all lesions before cryotherapy. Five hours after cryotherapy, all 10
      sBCCs showed small bright round to polygonal structures at basal layer and black
      round to oval areas of varying size with such bright structures floating therein,
      correlating to cell necrosis and incipient blistering. Eight sBCCs showed also
      cell necrosis in upper dermis. After 24h all sBCCs showed necrotic cells beneath
      collagen bundles. Tumour clearance on later histopathologic examination was only
      proven in those lesions showing damage to the upper dermis after 5h with RCM.
      CONCLUSION: Early cell necrosis within upper dermal structures seems to correlate
      with ablation of overlying tumour tissue. When it is not produced by cryotherapy,
      a second treatment should be considered.

PMID- 18829268
TI  - Low rates of somatic p53 mutations in keratoacanthomas.

PMID- 18829269
TI  - The dopamine agonist apomorphine differentially affects cognitive performance in
      alcohol dependent patients and healthy controls.
AB  - BACKGROUND: Reduced metabolic activity in frontal brain regions, and reduced
      striatal dopamine receptor densities have been shown in alcohol dependent
      patients. Little is known on functional changes in the fronto-striatal-thalamic
      dopaminergic neurocircuitry in these patients. The objective of this study was to
      assess sensitivity of prefrontal dopamine receptors in alcohol dependent
      patients. EXPERIMENTAL PROCEDURES: Male alcohol dependent patients (N=40) and
      healthy controls (N=39) performed an AX-continuous performance test before and
      after administration of the DA agonist apomorphine (0.005 mg/kg). RESULTS: At
      baseline alcohol dependent patients were slower and less accurate compared to
      healthy controls. After administration of apomorphine, performance improved in
      alcohol dependent patients and deteriorated in healthy controls. CONCLUSIONS:
      Reduced cognitive performance in alcohol dependent patients compared with healthy
      controls may indicate dopamine dysfunctioning at the prefrontal level.
      Improvement of cognitive performance in alcohol dependent patients after
      administration of apomorphine and deterioration in healthy controls provides
      evidence for an inverted U-shape relation between dopaminergic functioning and
      cognitive performance.

PMID- 18829270
TI  - Prediction of (207)Pb NMR parameters for the solid ionic lead(II) halides using
      the relativistic ZORA-DFT formalism: Comparison with the lead-containing
      molecular systems.
AB  - Density functional calculations of (207)Pb NMR shielding in PbX(2) (X=F, Br, Cl
      and I) anionic fragments suggest that in solid PbX(2), the observed variation of
      chemical shift with halide is dominated by the paramagnetic contribution to the
      chemical shielding, with a lesser effect by the spin-orbit contribution. The
      calculations include relativistic effects at the level of the zero-order regular
      approximation (ZORA). The present observation contrasts with previous
      calculations for the molecular system, PbX(4), in which the spin-orbit
      contribution has been shown to be the major factor in the variation of the NMR
      chemical shift.

PMID- 18829271
TI  - Vesicle formation in hydrocarbons assisted with microbial hydrolases and
      biosurfactants.
AB  - The present study demonstrates the role of microbial hydrolases in the
      transformation of hydrocarbons (soybean, sunflower, groundnut and gingelly oil,
      etc.) to vesicles. The combined effect of lipolytic enzyme generation and
      biosurfactants production during microbial growth at optimized media and
      environmental conditions mediates this transformation. Among the microbial
      species, Candida albicans exhibit complete transformation compared to
      Pseudomonads and Bacillus sps. Within hydrocarbons, only soybean and sunflower
      oils transformed to solid mass and no change with the remaining oils.
      Characterization of the vesicles revealed an increase in total weight by 160-180%
      compared to the original weight of hydrocarbon taken for the study and more than
      73% increases in viscosity. Acid value and saponification value also showed an
      increase, respectively, by 78 and 84%. The bound water content estimated was 26%.
      Light microscopic analysis exhibit, presence of unilamellar and bi-lamellar
      structures.

PMID- 18829272
TI  - Effect of PLGA as a polymeric emulsifier on preparation of hydrophilic protein
      loaded solid lipid nanoparticles.
AB  - Most proteins are hydrophilic and poorly encapsulated into the hydrophobic matrix
      of solid lipid nanoparticles (SLN). To solve this problem, poly (lactic-co
      glycolic acid) (PLGA) was utilized as a lipophilic polymeric emulsifier to
      prepare hydrophilic protein-loaded SLN by w/o/w double emulsion and solvent
      evaporation techniques. Hydrogenated castor oil (HCO) was used as a lipid matrix
      and bovine serum albumin (BSA), lysozyme and insulin were used as model proteins
      to investigate the effect of PLGA on the formulation of the SLN. The results
      showed that PLGA was essential for the primary w/o emulsification. In addition,
      the stability of the w/o emulsion, the encapsulation efficiency and loading
      capacity of the nanoparticles were enhanced with the increase of PLGA
      concentration. Furthermore, increasing PLGA concentration decreased zeta
      potential significantly but had no influence on particle size of the SLN. In
      vitro release study showed that PLGA significantly affected the initial burst
      release, i.e. the higher the content of PLGA, the lower the burst release. The
      released proteins maintained their integrity and bioactivity as confirmed by
      sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and
      biological assay. These results demonstrated that PLGA was an effective
      emulsifier for the preparation of hydrophilic protein-loaded SLN.

PMID- 18829273
TI  - [Antiepileptic drugs in pediatric migraine].
AB  - According to the criteria of the International Headache Society, migraine occurs
      in approximately 5 to 10% of children. As many as 30% of young patients with
      migraine experience such frequent and disabling attacks, or have unsatisfactory
      results and/or experience adverse effects with pharmacologic treatment of acute
      migraine attack, that daily preventive medications are required. Many studies
      have investigated the use of antiepileptic drugs in this indication but there is
      a paucity of placebo-controlled studies. So far, in the setting of migraine with
      and without aura, only flunarizine and topiramate have proved their efficacy in
      more than one placebo-controlled study. Uncontrolled studies suggest the possible
      efficacy of valproic acid, gabapentin, levetiracetam, zonisamide, and magnesium
      in preventive therapy of childhood periodic syndromes. Most of antiepileptic
      drugs used in pediatric preventive therapy are well tolerated. The most common
      adverse events are asthenia and somnolence.

PMID- 18829274
TI  - [Interfaces for pediatric noninvasive ventilation (excluding neonate)].
AB  - The quality of noninvasive ventilation in pediatrics is interface-dependent.
      Several types of interfaces are currently available: nasal and oral masks, nasal
      pillows and helmets. Despite material improvements in material design, shape,
      size and components, interfaces are still not adapted for most children. The
      ideal interface must fit the child's characteristics and the disease
      requirements. For instance, a nasal canula is recommended for infants younger
      than 3 months of age. If necessary, nasal masks can be used as oronasal masks.
      Repeated and careful evaluations are indicated to ensure interface adequacy and
      to detect cutaneous injuries and facial deformities. Training is required for
      medical and paramedical personnel. Pediatrics studies, comparing interfaces, are
      needed to build evidence-based recommendations.

PMID- 18829275
TI  - [Prevention of mother-to-child transmission of HIV in Gabon. The problem of
      children lost to follow-up].

PMID- 18829276
TI  - [Thoracic myopericytoma in a child. A case report].
AB  - Myopericytoma is a ubiquitous, benign tumor that is likely to be found in the
      muscular-cutaneous system. Symptoms are related to its location and to the mass
      effect it may cause on surrounding organs. Diagnosis is usually made by the
      pathologist and treatment is surgical. We report herein a rare thoracic location
      in a 4-year-old girl.

PMID- 18829277
TI  - [Digestive hemorrhage revealing a chronic esophageal foreign body. Report of a
      pediatric case].

PMID- 18829278
TI  - 3-Hydrogenkwadaphnine, a novel diterpene ester from Dendrostellera lessertii, its
      role in differentiation and apoptosis of KG1 cells.
AB  - 3-Hydrogenkwadaphnin (3-HK) (Fig. 1) is a daphnane-type diterpene ester isolated
      from the leaves of Dendrostellera lessertii (Thymelaeaceae) with differentiation
      and apoptotic potency among several leukemic cells without any measurable adverse
      effects on normal cells [Moosavi, M.A., Yazdanparast, R., Sanati, M.H., Nejad,
      A.S., 2005a. 3-Hydrogenkwadaphnin targets inosine 5'-monophosphate dehydrogenase
      and triggers post-G1 arrest apoptosis in human leukemia cell lines. Int. J.
      Biochem. Cell Biol. 37, 2366-2379]. In this study, we evaluated differentiating
      and apoptotic efficiency of a second new anti-proliferating agent from the same
      plant relative to 3-HK using acute myeloid leukemia (AML) KG1 cell line. 3-HK at
      5-30 nM inhibited proliferation of KG1 cells after 24-96 h of treatment. NBT
      reducing assay and expression of cell surface markers (CD11b and CD14) confirmed
      that the inhibition of proliferation is associated with differentiation toward
      macrophage-like morphology. Regarding the relatively weaker potency of 3-HK in
      the induction of differentiation compared to that of the crude extract, we looked
      for additional compound(s) with similar properties in the crude extract. This
      effort led to isolation of the second compound from the leaves' extract with
      higher differentiating potency. The new compound inhibited proliferation of KG1
      cells by almost 48+/-3.1% after 72 h of treatment with a single dose of 1.5
      microg/ml. The treated cells differentiated along the monocyte/macrophage lineage
      based on the morphological features apparent after Wright-Giemsa staining,
      phagocytic activity and expression of cell surface markers as analyzed by flow
      cytometry. On the other hand, the results indicated that exposure of KG1 cells to
      either 3-HK or the new compound for 3-4 days induced apoptosis as assayed
      qualitatively by acridine orange/ethidium bromide (Ao/EtBr) double staining,
      agarose gel electrophoresis and quantitatively by Annexin-V technique and sub-G1
      DNA staining using flow cytometry. Based on the present data, these two active
      constituents of D. lessertii have the novelty of being further evaluated for
      pharmaceutical applications.

PMID- 18829280
TI  - Inspired fraction of carbon dioxide in oxygen supply to chronic pulmonary
      disease.
AB  - Hypoxemic patients with chronic obstructive pulmonary disease (COPD) are at risk
      of carbon dioxide (CO(2)) retention during oxygen therapy and hypercapnia in COPD
      is associated with an ominous prognosis. Rebreathing with oxygen mask is possible
      in practice and possibly affects CO(2) retention due to an increased inspired
      fraction of CO(2). Its effects on arterial partial pressure of CO(2) during
      oxygen supply have, to the best of our knowledge, never been studied. We measured
      the inspired fraction of CO(2) in eighteen non-hypoxemic stable COPD patients
      with a capnograph during a 5 min trial with two different modes of oxygen supply
      (oxygen mask without reservoir bag and nasal prongs, respectively at a flow of 10
      l/min and 2l/min). We found no significant increase in inspiratory CO(2)
      concentration. These findings suggest that inspired fraction of CO(2) does not
      increase markedly during controlled oxygen therapy.

PMID- 18829279
TI  - COX-2 expression and function in the hyperalgesic response to paw inflammation in
      mice.
AB  - Peripheral inflammation and edema are often accompanied by primary and secondary
      hyperalgesia which are mediated by both peripheral and central mechanisms. The
      role of cyclooxygenase-2 (COX-2)-mediated prostanoid production in hyperalgesia
      is a topic of substantial current interest. We have established a murine foot-pad
      inflammation model in which both pharmacologic and genetic tools can be used to
      characterize the role of COX-2 in hyperalgesia. Zymosan, an extract from yeast,
      injected into the plantar surface of the hindpaw induces an edema response and an
      increase in COX-2 expression in the hindpaw, spinal cord and brain. Zymosan
      induced primary hyperalgesia, measured as a decrease in hindpaw withdrawal
      latency in response to a thermal stimulus, is long-lasting and is not inhibited
      by pre-treatment with the systemic COX-2 selective inhibitor, parecoxib (20
      mg/kg). In contrast, the central component of hyperalgesia, measured as a
      reduction in tail flick latency in response to heat, is reduced by parecoxib.
      Zymosan-induced primary hyperalgesia in Cox-2-/- mice is similar to that of their
      Cox-2+/+ littermate controls. However, the central component of hyperalgesia is
      substantially reduced in Cox-2-/- versus Cox-2+/+ mice, and returns to baseline
      values much more rapidly. Thus pharmacological data suggest, and genetic
      experiments confirm, (i) that primary hyperalgesia in response to zymosan
      inflammation in the mouse paw is not mediated by COX-2 function and (ii) that COX
      2 function plays a major role in the central component of hyperalgesia in this
      model of inflammation.

PMID- 18829281
TI  - Fasting triacylglycerol status, but not polyunsaturated/saturated fatty acid
      ratio, influences the postprandial response to a series of oral fat tolerance
      tests.
AB  - Elevated postprandial lipemia is emerging as a risk factor for obesity-related
      chronic diseases, such as type 2 diabetes and cardiovascular disease, and is
      associated with alterations in several metabolic biomarkers of disease. Our goal
      was to examine the effects of specific polyunsaturated/saturated fatty acid (P/S)
      ratios on postprandial triacylglycerol (TAG) concentrations and metabolic
      biomarkers in men with different fasting TAG concentrations through a series of
      oral fat tolerance tests (OFTT) consisting solely of emulsified lipid. Otherwise
      healthy men with high (>1.69 mmol/L) fasting TAG (HTAG, n=8) and low fasting TAG
      (LTAG, n=8) underwent three OFTTs with specific P/S ratios of 0.2, 1.0 and 2.0,
      respectively, and a total lipid load of 1 g/kg subject body mass. All subjects
      received each treatment separated by at least 1 week. Postprandial plasma TAG
      fatty acid composition reflected fatty acids present in the OFTT. All other
      metabolic responses were independent of the P/S ratio ingested. An accelerated
      increase in postprandial TAGs was observed in HTAG compared to LTAG. Interleukin
      (IL)-6 and soluble intercellular adhesion molecule (sICAM)-1 were significantly
      elevated in HTAG at baseline (P<.05). IL-6 increased significantly following each
      OFTT (P<.05) in both groups. Postprandial glucose and CRP were significantly
      exaggerated (P<.05) in HTAG. Overall, HTAG subjects had an accelerated
      postprandial TAG response and increased concentrations of several inflammatory
      markers following an OFTT, in the absence of an insulin response. However, P/S
      ratio had no influence on postprandial lipid and inflammatory parameters.

PMID- 18829282
TI  - Differential incorporation of dietary conjugated linolenic and linoleic acids
      into milk lipids and liver phospholipids in lactating and suckling rats.
AB  - Interest in health benefits of conjugated fatty acids is growing. The present
      study compared the incorporation pattern of dietary conjugated linolenic acids
      (CLnA) into milk with that of conjugated linoleic acids (CLA). Lactating Sprague
      Dawley rats (Day 1) were divided into five groups fed the control diet (n=4) or
      one of four experimental diets supplemented with 1-2% CLA or CLnA mixture (n=8
      each). Supplementation of 1% and 2% CLA led to enrichment of 4.17% and 8.57% CLA,
      respectively, while supplementation of 1% and 2% CLnA resulted in enrichment of
      only 0.98% and 1.71% CLnA in the milk lipids, demonstrating the transfer of CLnA
      from maternal diet to milk was discriminated. When the lactating rats were given
      a diet containing a CLnA mixture of 9t,11t,13t-, 9c,11t,13t- and 9c,11t,13c-CLnA
      isomers, two CLA isomers, namely, 9t,11t (0.59-0.90%) and 9c,11t (1.21-1.96%),
      were found in the milk, suggesting that three CLnA isomers were Delta-13
      saturated. Dietary CLnA at 1-2% had no effect on liver phospholipid (PL) fatty
      acid composition of both maternal and suckling rats, whereas dietary CLA
      increased docosahexaenoic acid (4c,7c,10c,13c,16c,19c-22:6) and palmitic acid
      (16:0) proportionally in the PL of maternal rats, but it suppressed 16:0 in the
      PL of suckling rats. It is concluded that maternal rats incorporate CLnA isomers
      into milk differently from that of CLA isomers. Most interesting is that maternal
      rats can metabolically convert CLnA to CLA.

PMID- 18829283
TI  - Mechanisms of nuclear vitamin D receptor resistance in Harvey-ras-transfected
      cells.
AB  - The hormone 1,25 dihydroxyvitamin D (1,25(OH)(2)D) binds to the nuclear vitamin D
      receptor (nVDR), which heterodimerizes with retinoid X receptor alpha (RXRalpha),
      and this complex interacts with specific response elements [vitamin D response
      elements (VDREs)] to regulate gene transcription. Previous results show a
      significant reduction in 1,25(OH)(2)D-induced nVDR transcriptional activity in
      fibroblast (C3H10T1/2) cells transfected with the Harvey ras gene (ras cells)
      compared with parental cells. The purpose of this study was to investigate the
      mechanisms by which the H-ras gene interferes with nVDR transcriptional activity.
      Similar to the ras cells, transcriptional activity of the nVDR was reduced
      following induction of the H-ras gene for 9 days. The ras cells expressed similar
      protein levels of RXRalpha with the parent cells, and overexpression of the wild
      type RXRalpha plasmid did not restore 1,25(OH)(2)D-mediated nVDR activity in ras
      cells. Inhibiting activation of extracellular signal-regulated kinase (ERK1/2)
      had no effect on nVDR activity in ras cells. Furthermore, the binding of nVDR to
      VDREs was reduced in 1,25(OH)(2)D-treated ras cells. In addition, neither
      treatment of ras cells with an inhibitor (ketoconazole) of the 1,25(OH)(2)D
      degradative enzyme, 24-hydroxylase, nor the protein kinase C inhibitors,
      bisindoylmaleimide I and Go 6976, had an effect on nVDR activity. In contrast,
      inhibition of phosphatidylinositol 3-kinase (PI3K) with LY294002 resulted in a
      1.6-fold significant increase in the nVDR activity in the ras cells. Taken
      together, these results indicate that PI3K may, at least in part, mediate the
      suppression of the 1,25(OH)(2)D regulation of nVDR transcriptional activity by
      the H-ras gene, leading to reduced ability to associate with response elements.

PMID- 18829284
TI  - The effect of long-term lactobacilli (lactic acid bacteria) enteral treatment on
      the central nervous system of growing rats.
AB  - The aim of this study was to explore the relationship between consumption of
      large doses of lactic acid bacteria (LAB) and the behaviour and brain
      morphobiochemistry of normal growing rats. Four groups of rats were treated with
      LAB cultures twice daily for 6 months. The control group received 1 ml of saline
      per treatment, while two experimental groups received 1 ml of living bacteria
      (Lactobacillus plantarum and Lactobacillus fermentum, respectively) and the
      remaining group received a heat-treated (inactivated) L. fermentum culture. After
      2 and 6 months of treatment, respectively, eight animals from each group were
      sacrificed, and specimens were taken for further analyses. The behaviour of the
      rats was evaluated five times in an open-field test at monthly intervals
      throughout the study. Lactobacilli treatment for 2 months induced changes in the
      motoric behaviour of the rats. The concentration of the astrocytesoluble and
      filament glial fibrillary acidic protein (GFAP) decreased in the posterior part
      of the hemispheres, including the thalamus, hippocampus and cortex of the rats
      treated with L. fermentum. A greater decrease in filament GFAP (up to 50%) was
      shown in the group receiving the live form of L. fermentum. In contrast, the GFAP
      in the live L. plantarum-treated group increased, showing elevated levels of the
      soluble and filament forms of GFAP in the posterior part of the hemispheres. A 60
      66% decrease in the amount of the astrocyte-specific Ca-binding protein S-100b
      was shown in the posterior parts of the hemispheres and in the hindbrain of rats
      given LAB for 2 months. Prolonged feeding with LAB for 4 months up to full
      adulthood led to a further decrease in astrocyte reaction, reflected as an
      additional decrease in the amount of soluble GFAP and locomotor activity in all
      experimental groups. The changes in filament GFAP and S-100b appeared to
      disappear after prolonged feeding (total of 6 months) with LAB. In summary, LAB
      dietary treatment affected the ontogenetic development of the astrocytes, with
      the highest intensity observed in the early stages of rat development. It can be
      postulated that LAB treatment may play a preventive role in neurological diseases
      by decreasing astrocyte reaction and, consequently, lowering locomotor activity.

PMID- 18829285
TI  - Down-regulation in muscle and liver lipogenic genes: EPA ethyl ester treatment in
      lean and overweight (high-fat-fed) rats.
AB  - The precise mechanisms by which omega-3 fatty acids improve fat metabolism are
      not completely understood. This study was designed to determine the effects of
      eicosapentaenoic acid (EPA) ethyl ester administration on the expression levels
      of several muscle, liver and adipose tissue genes involved in lipogenesis and
      fatty acid oxidation pathways. Male Wistar rats fed a standard diet (control
      animals) or a high-fat diet were treated daily by oral gavage with EPA ethyl
      ester (1g/kg) for 5 weeks. The high-fat diet caused a very significant increase
      in plasma cholesterol (P<.01) levels, which was reverted by EPA (P<.001). A
      significant decrease in circulating triglyceride levels (P<.05) was also observed
      in EPA-treated groups. EPA administration induced a significant down-regulation
      in some lipogenic genes such as muscle acetyl CoA carboxylase beta (ACC beta)
      (P<.05) and liver fatty acid synthase (FAS) (P<.05). Furthermore, a decrease in
      glucokinase (GK) gene expression was observed in EPA-treated animals fed a
      control diet (P<.01), whereas a significant increase in GK mRNA levels was found
      in groups fed a high-fat diet. On the other hand, no alterations in genes
      involved in beta-oxidation, such acetyl CoA synthase 4 (ACS4), acetyl CoA
      synthase 5 (ACS5) or acetyl CoA oxidase (ACO), were found in EPA-treated groups.
      Surprisingly and opposite to the expectations, a very significant decrease in the
      expression levels of liver PPARalpha (P<.01) was observed after EPA treatment.
      These findings show the ability of EPA ethyl ester treatment to down-regulate
      some genes involved in fatty acid synthesis without affecting the transcriptional
      activation of beta-oxidation-related genes.

PMID- 18829286
TI  - The gastrointestinal microbiota affects the selenium status and selenoprotein
      expression in mice.
AB  - Colonization of germ-free (GF) mice has been shown to induce the gastrointestinal
      form of the selenium-dependent glutathione peroxidases, GPx2. Since bacterial
      colonization of the gastrointestinal tract is associated with stress, we aimed to
      clarify how bacteria affect selenoprotein expression in unstressed conditions. GF
      and conventional (CV) FVB/NHan(TMHsd) mice were fed a selenium-poor (0.086 ppm)
      or a selenium-adequate (0.15 ppm) diet for 5 weeks starting from weaning. Each
      group consisted of five animals. Specific glutathione peroxidase (GPx) and
      thioredoxin reductase (TrxR) expression was measured in plasma, liver and
      intestinal sections by activity, protein and mRNA level as appropriate. Under
      selenium-adequate conditions, selenoprotein expression did not differ in GF and
      CV mice. Under selenium-limiting conditions, however, GF mice generally contained
      higher GPx and TrxR activities in the intestine and liver, higher GPx1 protein
      and RNA levels in the liver, higher GPx2 protein levels in the proximal and
      distal jejunum and colon and higher GPx1 and GPx2 RNA levels in the colon. In
      addition, higher selenium concentrations were estimated in plasma, liver and
      cecum. All differences were significant. It is concluded that bacteria may
      compete with the host for selenium when availability becomes limiting. A variable
      association with different microorganisms might influence the daily requirement
      of mice for selenium. Whether the microbiota also affects the human selenoprotein
      status appears worthy of investigation.

PMID- 18829287
TI  - The influence of orally administered docosahexaenoic acid on cognitive ability in
      aged mice.
AB  - The purpose of this study was to investigate whether or not the role of
      docosahexaenoic acid (DHA) supplementation on cognitive capability was related
      with brain-derived neurotrophic factor (BDNF), nitric oxide (NO) and dopamine
      (DA) in aged mice. Kunming-line mice were treated with 50 and 100 mg/kg/day of
      DHA via oral gavage for seven successive weeks. The cognitive ability of mice was
      assessed by step-through and passageway water maze tests. The levels of NO in
      hippocampus and striatum tissues were assessed by spectrophotometric method. The
      levels of DA in hippocampus and striatum tissues were assessed by high
      performance liquid chromatography with electrochemical detection. The protein
      levels of BDNF in hippocampus tissue were assessed by Western blotting. The
      results showed that the cognitive capability of mice was significantly different
      between the DHA-treated groups and the control group; the protein level of BDNF
      was significantly increased in the hippocampus; the levels of NO and DA were
      significantly increased in hippocampus and striatum tissues. In conclusion,
      during aging, DHA supplementation can improve the cognitive function in mice and
      can increase the protein level of BDNF in hippocampus tissue and the levels of NO
      and DA in hippocampus and striatum tissues. Taken together, our results suggest
      that DHA supplementation could improve the cognitive dysfunction due to aging, to
      some extent, and it may have a relationship with increasing the protein level of
      BDNF and the level of NO and DA.

PMID- 18829288
TI  - Comparative environmental analysis of waste brominated plastic thermal
      treatments.
AB  - The aim of this research activity is to investigate the environmental impact of
      different thermal treatments of waste electric and electronic equipment (WEEE),
      applying a life cycle assessment methodology. Two scenarios were assessed, which
      both allow the recovery of bromine: (A) the co-combustion of WEEE and green waste
      in a municipal solid waste combustion plant, and (B) the staged-gasification of
      WEEE and combustion of produced syngas in gas turbines. Mass and energy balances
      on the two scenarios were set and the analysis of the life cycle inventory and
      the life cycle impact assessment were conducted. Two impact assessment methods
      (Ecoindicator 99 and Impact 2002+) were slightly modified and then used with both
      scenarios. The results showed that scenario B (staged-gasification) had a
      potentially smaller environmental impact than scenario A (co-combustion). In
      particular, the thermal treatment of staged-gasification was more energy
      efficient than co-combustion, and therefore scenario B performed better than
      scenario A, mainly in the impact categories of "fossil fuels" and "climate
      change". Moreover, the results showed that scenario B allows a higher recovery of
      bromine than scenario A; however, Br recovery leads to environmental benefits for
      both the scenarios. Finally the study demonstrates that WEEE thermal treatment
      for energy and matter recovery is an eco-efficient way to dispose of this kind of
      waste.

PMID- 18829289
TI  - Pay-as-you-throw - a tool for urban waste management.

PMID- 18829290
TI  - Municipal solid waste management in India: From waste disposal to recovery of
      resources?
AB  - Unlike that of western countries, the solid waste of Asian cities is often
      comprised of 70-80% organic matter, dirt and dust. Composting is considered to be
      the best option to deal with the waste generated. Composting helps reduce the
      waste transported to and disposed of in landfills. During the course of the
      research, the author learned that several developing countries established large
      scale composting plants that eventually failed for various reasons. The main flaw
      that led to the unsuccessful establishment of the plants was the lack of
      application of simple scientific methods to select the material to be composted.
      Landfills have also been widely unsuccessful in countries like India because the
      landfill sites have a very limited time frame of usage. The population of the
      developing countries is another factor that detrimentally impacts the function of
      landfill sites. As the population keeps increasing, the garbage quantity also
      increases, which, in turn, exhausts the landfill sites. Landfills are also
      becoming increasingly expensive because of the rising costs of construction and
      operation. Incineration, which can greatly reduce the amount of incoming
      municipal solid waste, is the second most common method for disposal in developed
      countries. However, incinerator ash may contain hazardous materials including
      heavy metals and organic compounds such as dioxins, etc. Recycling plays a large
      role in solid waste management, especially in cities in developing countries.
      None of the three methods mentioned here are free from problems. The aim of this
      study is thus to compare the three methods, keeping in mind the costs that would
      be incurred by the respective governments, and identify the most economical and
      best option possible to combat the waste disposal problem.

PMID- 18829291
TI  - From traditional to modern fee systems.
AB  - This paper deals with the environmentally important issue regarding how best to
      motivate citizens to reduce their individual waste production. The paper
      discusses the pros and cons of the various financial incentives incorporated into
      the waste charging mechanism, pay-as-you-throw (PAYT). Pay-as-you-throw breaks
      with the tradition of paying for waste services through general blanket taxes or
      levies in the form of flat rates in that households are required to pay
      individually adjusted fees in the same way as water and electricity bills are
      calculated on an individual consumption basis. This difference is achieved
      through the interplay of three principal components which mark the technical
      implementation of PAYT: identification as a vehicle to attain accountability,
      measurement of the generated waste and/or corresponding services, and unit
      pricing as the basis for individual charges proportional to the extent of the
      obtained services. However, any motivating factor for inducing citizens to
      dispose of their recyclable discards and residual waste must be supported by a
      well developed collection infrastructure, good media information and an
      appropriate, transparent charging policy. Of particular importance is the use of
      a multi-tiered charge model, i.e., the charging of a fixed minimum fee plus
      certain variable components payable in respect of the service structure. The
      introduction of a basic charge, albeit reducing the intensity of the incentives
      created by the PAYT system, ensures that certain fixed costs for the provision of
      waste services will be covered independently from the actual waste developments
      and, at the same time, minimises the temptation to attempt to bypass the system.
      Such an arrangement for the waste charges neither contradicts the principle of
      pay-as-you-throw nor does it impair the waste diversion for which it is
      implemented. Waste statistics and figures representing the waste charging
      situation in Germany indicate that there is a relatively good correlation between
      the level of recycling and the amount of perceived financial motivation provided
      by PAYT. Waste stream developments in areas using such charging schemes generally
      suggest that the reduction goals are being achieved. Single figures on decreasing
      quantities of collected residual waste, however, say little about the actual
      efficiency of differentiated waste charging models and deliver little in the way
      of reasoned explanation as to why the diffusion of variable rate pricing is
      progressing painstakingly slowly. To evaluate the success, feasibility and
      problems of PAYT schemes, one needs to consider the various ways for technically
      implementing this approach in practice, and must take a broader look into the
      wide spectrum of available waste services and into more factors that influence
      their efficiency and acceptance. Urban structure settings assume a particular
      importance here as do the specific goals of social policy which, among others,
      are reflected in the charging mechanisms applied. Practical experience, however,
      shows that solutions can be found which allow most of the concerns and area
      specifics to be accommodated and waste streams to be influenced in the desired
      way. Aside from this, positive effects as to waste collection efficiency can also
      be achieved, which contribute towards long-term environmental improvements and
      countervail the incremental costs of implementing PAYT.

PMID- 18829292
TI  - Investigation on the heavy metal content of zinc-carbon and alkaline manganese
      dry cells.
AB  - The objective of this work was to test the compliance of commercially available
      batteries with the German Battery Ordinance, a project of the German government
      that was initiated by the Federal Environment Agency. Different types of
      commercially available dry cells were analysed for their cadmium, lead and
      mercury contents. The dry cells underwent mechanical pre-treatment, separation of
      the different components and microwave-assisted digestion before determination of
      the heavy metals. Mercury is sometimes added to prevent the generation of gaseous
      hydrogen from the electrochemical process. Lead could be present since it is
      sometimes used as an alloying element of zinc. Cadmium has no technical
      importance and is an undesirable impurity. None of the batteries contained higher
      heavy metal mass fractions than the permissible limits.

PMID- 18829293
TI  - Detection of pesticide residues using an immunodevice based on negative
      dielectrophoresis.
AB  - The detection of atrazine using a novel optical immunosensing technique based on
      negative dielectrophoresis (n-DEP) in microfluidic channels is described.
      Atrazine is a toxic triazine herbicide within the most frequently used.
      Polystyrene microparticles (6 microm diameters) modified with bovine serum
      albumin conjugated with atrazine (atrazine-BSA) were manipulated and captured
      when subjected to intense n-DEP electric fields. Specifically, particles were
      trapped when AC voltages with amplitudes of 10 V(peak) and frequencies over 1 MHz
      were applied to the electrodes. The immunological reaction occurring on the
      particles for detecting atrazine is based on an indirect competitive assay using
      a secondary anti-mouse immunogloburin G (IgG) antibody labeled with fluorescein
      isothiocyanate. The microfluidic device, with three-dimensional microelectrodes,
      was fabricated comprising two caged areas, allowing two simultaneous measurements
      inside the same microfluidic channel. The performance of this n-DEP immunosensing
      technique was evaluated using wine samples. The immunodevice showed a limit of
      detection for atrazine in buffer samples of 0.11 microgL(-1) and in pre-treated
      wine samples of 6.8 microg L(-1); these detection limits are lower than the
      maximum residue level (MRL) established by the European Community for residues of
      this herbicide in wine (50 microg L(-1)). This methodology offers great promise
      for rapid, simple, cost effective, and on-site analysis of biological, foods and
      beverages, and environmental samples.

PMID- 18829294
TI  - Combination of aptamer with gold nanoparticles for electrochemical signal
      amplification: application to sensitive detection of platelet-derived growth
      factor.
AB  - In this paper, we report a novel electrochemical detection approach for platelet
      derived growth factor (PDGF) via "sandwich" structure and gold nanoparticles (Au
      NPs) mediated amplification technique. The "sandwich" structure is fabricated
      based on the fact that PDGF has two aptamer-binding sites, which makes it
      possible for one PDGF molecule to connect with two aptamers simultaneously. It is
      found that this electrochemical system with "sandwich" structure and Au-NPs can
      significantly amplify the signal of electrochemical probe [Ru(NH(3))(5)Cl](2+)
      for PDGF detection, and thus increase the detection sensitivity significantly. As
      a result, this PDGF detection approach obtains an extraordinarily low detection
      limit of 1 x 10(-14)M for purified samples, 1 x 10(-12)M for contaminated-ridden
      samples or undiluted blood serum. This detection approach can also exhibit good
      stability and excellent specificity.

PMID- 18829295
TI  - Development of antibody array for simultaneous detection of foodborne pathogens.
AB  - Pathogenic bacterial contaminations present serious problems for food industry
      and public health. Rapid, accurate and affordable assays are needed. In this
      study, antibody arrays to simultaneously detect two foodborne pathogenic bacteria
      (Escherichia coli O157:H7 and Salmonella spp.) have been developed using
      chemiluminescent detecting system. Solid supports using nitrocellulose membrane
      and poly-l-lysine (PLL) glass slide were compared and optimized for antibody
      array construction. Many parameters including optimal concentrations of
      antibodies, blocking reagents, assay time, storage time, sensitivity and cross
      reactivity were considered during optimization. This study revealed that the PLL
      slide was a more suitable support due to highly accurate results and the absence
      of non-specific background. Phosphate-buffered saline (PBS, pH 7.2) and 3% skim
      milk in PBS buffer were optimal spotting and blocking reagents, respectively.
      With the same sensitivity for bacterial detection as in a conventional ELISA
      (10(5)-10(6)CFU/ml for the E. coli O157:H7 and 10(6)-10(7)CFU/ml for Salmonella
      detections), this antibody array has advantages of a much shorter assay time of
      1h and much lower required amounts of antibodies. Moreover, there was no cross
      reactivity in the detection among bacteria tested in this study. Bacteria
      detection in food sample was feasible as demonstrated using bacteria-added milk.

PMID- 18829296
TI  - Ultra-sensitive immunosensor for beta-amyloid (1-42) using scanning tunneling
      microscopy-based electrical detection.
AB  - An ultra-sensitive immunosensor for beta-amyloid is crucial because beta-amyloid
      is an important challenging marker to detect for early diagnosis of Alzheimer's
      disease. In this study, a vertically configured electrical detection system was
      developed based on scanning tunneling microscopy (STM) to detect antigen-antibody
      binding events. This technique could be used to easily construct a multiple
      measurement system in a biochip. We utilized immunocomplexes comprised of the
      model protein, beta-amyloid (1-42), corresponding antibody fragments, and gold
      (Au) nanoparticles-antibody conjugates for an immunosensor for Alzheimer's
      disease. The electrical tunneling current between the STM tip and these complexes
      exhibited a peak-like pulse, the frequency of which depended on the density of
      the bound complexes on the surface. We could therefore quantitatively measure
      beta-amyloid (1-42) concentrations as low as 10fg/mL using periodogram analysis
      of the peak frequency. Since this method accurately quantified much smaller
      amounts of beta-amyloid (1-42) than traditional immunosensors, this system shows
      promise as an ultra-sensitive immunodetection method.

PMID- 18829297
TI  - Fullerene-C60-modified edge plane pyrolytic graphite electrode for the
      determination of dexamethasone in pharmaceutical formulations and human
      biological fluids.
AB  - Electrochemical behaviour of dexamethasone at the fullerene-C(60)-modified
      pyrolytic graphite electrode (PGE) has been investigated using Osteryoung square
      wave voltammetry (SWV). Compared to a bare PGE and fullerene-C(60)-modified
      glassy carbon electrode (GCE), the fullerene-C(60)-modified edge plane PGE
      exhibited an apparent shift of the peak potential to less negative potentials
      with a marked enhancement in the current response of dexamethasone. The peak
      potential was linearly dependent on pH with dE(p)/dpH as 59 mV/pH. Calibration
      plot having good linearity with a correlation coefficient 0.9983 is obtained in
      the concentration range of 0.05-100 microM and the sensitivity of the method has
      been found to be 0.685 microA microM(-1). The detection limit is estimated to be
      5.5 x 10(-8)M. The electrode showed good sensitivity, stability and
      reproducibility. The practical analytical utility of the method is illustrated by
      quantitative determination of dexamethasone in several commercially available
      pharmaceutical formulations and human blood plasma of patients being treated with
      dexamethasone. HPLC method was used to compare the results obtained for the
      quantitative estimation of dexamethasone in biological fluids.

PMID- 18829298
TI  - Polyazetidine-based immobilization of redox proteins for electron-transfer-based
      biosensors.
AB  - A highly stable functional composite film was prepared using polyazetidine
      prepolymer (PAP) with peroxidase from horseradish (HRP) and/or glucose oxidase
      (GOx). The good permeability of the PAP layer to classical electrochemical
      mediators, as evaluated by the determination of the diffusion coefficient of
      different redox molecules, is of great importance in view of the use of PAP as an
      immobilizing agent in second-generation biosensor development. Cyclic voltammetry
      of the HRP-PAP layer on a glassy carbon electrode (GCE) showed a pair of stable
      and quasi-reversible peaks for the HRP-Fe((III))/Fe((II)) redox couple at about 
      370 mV vs. Ag/AgCl electrode in pH 6.5 phosphate buffer. The electrochemical
      reaction of HRP entrapped in the PAP film exhibited a surface-controlled
      electrode process. This film and the successive modifications (HRP-PAP self
      assembled monolayer (SAM) modified Au electrode) were used as a biological
      catalyst (hydrogen peroxide transducers) for glucose biosensors, after coupling
      to GOx. Both HRP/GOx-PAP and HRP/GOx-PAP SAM third generation biosensors were
      prepared and characterized. The use of PAP as immobilizing agent offers a
      biocompatible micro-environment for confining the enzyme and foreshadows the
      great potentiality of this immobilizing agent not only in theoretical studies on
      protein direct electron transfer but also from an applications point of view in
      the development of second- and third-generation biosensors.

PMID- 18829300
TI  - Direct electrochemistry of myoglobin based on ionic liquid-clay composite films.
AB  - The direct electron transfer of myoglobin (Mb) was realized by immobilizing Mb
      onto ionic liquid (1-butyl-3-methyl imidazolium tetrafluoraborate, [bmim][BF(4)])
      clay composite film modified glassy carbon electrode. A pair of well-defined
      redox peaks of Mb with a formal potential (E(o)') of -0.297 V (vs. Ag/AgCl) was
      observed in 0.1M phosphate buffer solution (pH 6.0). The ionic liquid-clay
      composite film showed good biocompatibility and an obvious promotion capability
      for the direct electron transfer between Mb and electrode. The electron transfer
      rate constant (k(s)) of Mb was calculated to be (3.58+/-0.12)s(-1). UV-vis
      spectrum suggested that Mb retained its native conformation in the ionic liquid
      clay system. Basal plane spacing of clay obtained by X-ray diffraction (XRD)
      indicated that there was an intercalation-exfoliation-restacking process, in
      ionic liquid and clay during the drying process of the modification, and the
      ionic liquid played the key role for promotion of the direct electron transfer
      between Mb and the ionic liquid-clay composite film modified electrode. The
      biocatalytic activity of Mb in the composite film was exemplified by the
      reduction of hydrogen peroxide. Under the optimal conditions, the reduction peak
      currents of Mb increased linearly with the concentration of H(2)O(2) in the range
      of 3.90 x 10(-6) to 2.59 x 10(-4)M, with a detection limit of 7.33 x 10(-7)M. The
      kinetic parameter I(max) and the apparent Michaelis constant (K(m)) for the
      electrocatalytic reactions were 3.87 x 10(-8)A and 17.6 microM, respectively. The
      proposed method would be valuable for the construction of a new third-generation
      H(2)O(2) sensor.

PMID- 18829299
TI  - Revisited BIA-MS combination: entire "on-a-chip" processing leading to the
      proteins identification at low femtomole to sub-femtomole levels.
AB  - We present the results of a study in which biomolecular interaction analysis
      (BIA, Biacoretrade mark 2000) was combined with mass spectrometry (MS) using
      entire "on-a-chip" procedure. Most BIA-MS studies included an elution step of the
      analyte prior MS analysis. Here, we report a low-cost approach combining Biacore
      analysis with homemade chips and MS in situ identification onto the chips without
      elution step. First experiments have been made with rat serum albumin to
      determine the sensitivity and validation of the concept has been obtained with an
      antibody/antigen couple. Our "on-a-chip" procedure allowed complete analysis by
      MS/MS(2) of the biochip leading to protein identifications at low femtomole to
      sub-femtomole levels. Using this technique, identification of protein complexes
      were routinely obtained giving the opportunity to the "on-a-chip" processing to
      complete the BIA-MS approach in the discovery and analysis of protein complexes.

PMID- 18829301
TI  - Cervical, endometrial and ovarian cancers among immigrants in Sweden: importance
      of age at migration and duration of residence.
AB  - In order to compare the risk of gynaecologic cancer among foreign-born women to
      the risk among those born in Sweden and to elucidate risk of cancer in relation
      to age at migration and duration of residence, we followed a cohort of 5.3
      million women between 1969 and 2004 in Sweden. Through linkage with the national
      cancer register, we estimated cancer risk as rate ratios (RRs) with 95%
      confidence intervals (CIs) using Poisson regression. We reported RRs adjusted for
      age, calendar year of follow-up and years of education. Overall, 18,247 cases of
      cervical, 35,290 cases of endometrial and 32,227 cases of ovarian cancers
      occurred during 117 million person-years of follow-up. We found that adjusted RRs
      of all the three cancers were lower or the same among foreign-born women compared
      to those born in Sweden. As for cervical cancer, women aged 35-49 years born in
      Poland and Bosnia and women aged 50 years or more born in South America showed an
      increased risk, which was related to increasing age at migration. The risk was
      lowest among women born in Iran, Iraq, Organisation for Economic Cooperation &
      Development (OECD) and Finland, and highest among women born in Bosnia and
      Eastern Europe during their first 5 years since immigration. RRs for endometrial
      and ovarian cancers did not vary by duration of residence or by age at migration.
      Health care providers should be aware of the higher risk of cervical cancer among
      immigrants from high-risk areas, especially among those who immigrate at older
      ages. On the other hand, protective factors for ovarian and endometrial cancers
      seem to be retained upon migration.

PMID- 18829303
TI  - Thermal analysis and devolatilization kinetics of cotton stalk, sugar cane
      bagasse and shea meal under nitrogen and air atmospheres.
AB  - Thermal degradation, reactivity and kinetics for biomass materials cotton stalk
      (CS), sugarcane bagasse 1 (SB1), sugarcane bagasse 2 (SB2) and shea meal (SM)
      have been evaluated under pyrolysis (N(2)) and oxidising (dry air) conditions,
      using a non-isothermal thermogravimetric method (TGA). In the cases of CS and SB1
      the peak temperatures were 51 degrees C higher for pyrolysis compared with
      oxidative degradation, whereas for SB2 and SM the difference was approximately 38
      degrees C. However, the differences in the rates of weight loss were
      significantly higher under oxidising conditions for all the materials studied.
      Maximum rate of weight loss (%s(-1)) under pyrolysis conditions ranged from 0.10
      to 0.18 whereas these values accelerated to the range of 0.19-0.28 under
      oxidising conditions, corresponding to respective peak temperatures. Samples
      ranked in order of reactivity (R(M)x10(3)) (%s(-1) degrees C(-1)) are CS=1.31
      approximately SM=1.30>SB2=1.14>SB1=0.94 for air and
      CS=0.54>SB2=0.49>SB1=0.45>SM=0.31 for nitrogen. Shea meal exhibited a complex
      char combustion behaviour indicating that there may be two distinct types of char
      derived from fibrous and woody components in the original material. Activation
      energy calculations were based on the Arrhenius correlation.

PMID- 18829302
TI  - Recent advances in the treatment of renal cell carcinoma and the role of targeted
      therapies.
AB  - Immunotherapy confers a small but significant overall survival advantage in
      metastatic renal cell carcinoma (RCC) but only for the minority of patients, i.e.
      the 20% with good prognostic features. Recent developments in the molecular
      biology of renal cell carcinoma have identified multiple pathways associated with
      the development of this cancer. Several strategies have been investigated
      targeting these pathways, with significant clinical benefits shown in early
      studies. New agents including the small molecule targeted inhibitors sunitinib,
      sorafenib and temsirolimus, and the monoclonal antibody bevacizumab have shown
      anti-tumour activity in randomised clinical trials and have become the standard
      of care for most patients. Sunitinib and temsirolimus have shown significant
      improvements in progression-free survival (sunitinib) and overall survival
      (temsirolimus) in separate phase III studies in the first-line setting when
      compared with interferon-alpha. Sorafenib has demonstrated prolonged progression
      free survival in a phase III study in comparison with placebo in the second-line
      setting. More recently two phase III studies have compared bevacizumab and
      interferon-alpha with interferon-alpha alone. Both studies showed a statistically
      significant improvement in progression-free survival for the combination arm.
      Additional studies are needed to optimise the use of these agents by identifying
      those patients who most benefit and elucidating the best way of delivering them,
      either in combination or as sequential single agents.

PMID- 18829304
TI  - Effects of L-cysteine on Ni-Cu sulfide and marmatite bioleaching by
      Acidithiobacillus caldus.
AB  - The effect of L-cysteine in different concentrations on the bioleaching of Ni-Cu
      sulfide and marmatite were studied with a moderately thermophilic, sulfur
      oxidizing bacterium, strain of Acidithiobacillus caldus. X-ray diffraction (XRD)
      observations showed the change of bioleached solid residues and the effect of L
      cysteine on the surface charges of minerals. It was found that adding certain
      amounts of L-cysteine to the leaching system of Ni-Cu sulfide largely enhanced
      the leaching rate, while L-cysteine inhibited the bioleaching of marmatite by A.
      caldus. The mechanism of L-cysteine interaction with mineral surfaces was studied
      by means of zeta potential determination and IR spectra.

PMID- 18829305
TI  - Enhancing the adsorption capacities of acid dyes by chitosan nano particles.
AB  - In the present study, nanochitosan emulsion has been produced in a suspension
      form by adding tripolyphosphate solution into a chitosan solution drop-wise. The
      adsorption capacities of four acid dyes, namely, Acid Orange 10 (AO10), Acid
      Orange 12 (AO12), Acid Red 18 (AR18) and Acid Red 73 (AR73) on nanochitosan, have
      been determined to be 1.77, 4.33, 1.37 and 2.13 mmol l(-1), respectively. The
      nanochitosan dye capacities were compared with normal chitosan capacities which
      were 1.54, 2.66, 1.11 and 1.25 mmol l(-1) for AO10, AO12, AR18 and AR73,
      respectively. In all cases, the nanochitosan has a higher capacity. The mechanism
      of acid dye adsorption and the effect of pH are also discussed.

PMID- 18829306
TI  - Comparison of non-catalytic and catalytic fast pyrolysis of corncob in a
      fluidized bed reactor.
AB  - Fast pyrolysis of corncob with and without catalyst was investigated in a
      fluidized bed to determine the effects of pyrolysis parameters (temperature, gas
      flow rate, static bed height and particle size) and a HZSM-5 zeolite catalyst on
      the product yields and the qualities of the liquid products. The result showed
      that the optimal conditions for liquid yield (56.8%) were a pyrolysis temperature
      of 550 degrees C, gas flow rate of 3.4 L/min, static bed height of 10 cm and
      particle size of 1.0-2.0mm. The presence of the catalyst increased the yields of
      non-condensable gas, water and coke, while decreased the liquid and char yields.
      The elemental analysis showed that more than 25% decrease in oxygen content of
      the collected liquid in the second condenser with HZSM-5 was observed compared
      with that without catalyst. The H/C, O/C molar ratios and the higher heating
      value of the oil fraction in the collected liquid with the catalyst were 1.511,
      0.149 and 34.6 MJ/kg, respectively. It was indicated that the collected liquid in
      the second condenser had high qualities and might be used as transport oil.

PMID- 18829307
TI  - Studies on the synthesis of neamine-dinucleosides and neamine-PNA conjugates and
      their interaction with RNA.
AB  - Two types of neamine derivatives, neamine-dinucleotide conjugates 8a-g and
      neamine-PNA conjugates 12a-c and 14a-d, were synthesized. Compound 8a-g were
      synthesized by the condensation of azido-neamine with dinucleotide-5'-carboxylic
      acids, followed by reduction and deprotection. Compound 12a-c and 14a-d were
      synthesized by the similar strategy. The binding affinities of conjugates 8a-g,
      12a-c, and 14a-d towards 16S RNA, 18S RNA, and TAR RNA were evaluated by SPR. It
      indicates that conjugates 12a-c and 14a-d interact with 16S, 18S RNA at the same
      level as that of neamine, 14a and 14d show about twofold binding affinities to
      TAR RNA compared to that of neamine. However, the neamine-dinucleotide conjugates
      8a-g exhibit very weak binding affinities to 16S, 18S, and TAR RNA, computer
      modelling results that negative-negative electrostatic repulsion of phosphate
      group in compound 8a-g and RNA leads to a sharp decrease of the binding
      affinities compared with that of neamine, neamine-nucleoside and neamine-PNA
      conjugates.

PMID- 18829308
TI  - Use of the X-ray structure of the beta2-adrenergic receptor for drug discovery.
      Part 2: Identification of active compounds.
AB  - The recently published X-ray structures of the beta(2)-adrenergic receptor are
      the first examples of ligand-mediated GPCR crystal structures. We have previously
      performed computational studies that examine the potential viability of these
      structures for use in drug design, exploiting known ligand activities. Our
      previous study and a newly reported beta(2)/Timolol X-ray complex provide
      validation of the computational approaches. In the present work, we use the X-ray
      structures to extract, via in silico high-throughput docking, compounds from
      proprietary and commercial databases and demonstrate the successful
      identification of active compounds by radioligand binding.

PMID- 18829309
TI  - Assembly system of direct modified superparamagnetic iron oxide nanoparticles for
      target-specific MRI contrast agents.
AB  - We report the direct modification of SPIOs with a biomolecule and the target
      specific assembly system of these modified SPIOs for using MRI contrast agents.
      The transverse relaxation rate of the aqueous solutions containing the modified
      SPIOs was altered by the dispersion state.

PMID- 18829310
TI  - Pholasin luminescence is enhanced by addition of dehydrocoelenterazine.
AB  - Pholasin is a bioluminescent photoprotein of Pholas dactylus. Pholasin is a
      commercially available photoprotein used to measure intracellular reactive oxygen
      species. Although extensive efforts have been carried out to determine the
      chemical structure of the prosthetic (chromophore) group, it still remains
      unclear to date. Herein, we report the enhancement of pholasin luminescence by
      the addition of dehydrocoelenterazine, which is organic substance of luminous
      squids' photoprotein.

PMID- 18829312
TI  - Novel 5-HT(1A/1B/1D) receptors antagonists with potent 5-HT reuptake inhibitory
      activity.
AB  - Novel 2-methyl-5-quinolinyl-1-piperazinylalkyl-3,4-dihydro-2H-1,4-benzoxazin-3
      ones showing high affinities for the 5-HT(1A/1B/1D) receptors coupled with potent
      5-HT reuptake inhibitory activity have been discovered. This is the first report
      describing docking of the lead compound 6-{2-[4-(2-methyl-5-quinolinyl)-1
      piperazinyl]ethyl}-2H-1,4-benzoxazin-3(4H)-one 1, into a model of the 5-HT
      transporter and the 5-HT(1A) receptor model.

PMID- 18829311
TI  - Synthesis and SAR of analogs of the M1 allosteric agonist TBPB. Part II: Amides,
      sulfonamides and ureas--the effect of capping the distal basic piperidine
      nitrogen.
AB  - This letter describes the further synthesis and SAR, developed through an
      iterative analog library approach, of analogs of the highly selective M1
      allosteric agonist TBPB by deletion of the distal basic piperidine nitrogen by
      the formation of amides, sulfonamides and ureas. Despite the large change in
      basicity and topology, M1 selectivity was maintained.

PMID- 18829313
TI  - Human serum albumin as a catalyst of RNA cleavage: N-homocysteinylation and N
      phosphorylation by oligonucleotide affinity reagent alter the reactivity of the
      protein.
AB  - Kinetic parameters for the cleavage of UpA site in an oligonucleotide in the
      presence of human serum albumin (HSA) or one of its clinically relevant
      modification were measured. The RNA-hydrolyzing activity of HSA was decreased by
      its nonenzymatic N-homocysteinylation. According to (31)P NMR data, Lys and Tyr
      residues were the labeling targets when a phosphorylating analog of
      oligoribonucleotide substrate was employed. The site of tyrosine modification was
      slowly dephosphorylated. Lys-directed affinity labeling suppressed
      oligonucleotide cleavage indicating that lysines took part in the reaction.

PMID- 18829314
TI  - Synthesis of novel benzamidine- and guanidine-derived polyazamacrocycles:
      Selective anti-protozoal activity for human African trypanosomiasis.
AB  - Efficient synthetic routes have been developed for the preparation of two new
      polyazamacrocycles tagged with structural motifs recognised by the Trypanosoma
      brucei P2 aminopurine transporter. Biological testing of these compounds showed
      highly selective anti-protozoal activity against trypanosomes.

PMID- 18829315
TI  - Design, synthesis and RNase A inhibition activity of catechin and epicatechin and
      nucleobase chimeric molecules.
AB  - Several novel catechin/epicatechin and nucleobase chimeric molecules 1-6 have
      been synthesized via azide-alkyne click chemistry. The structures of these
      hybrids have been confirmed by NMR and mass spectroscopic data. The synthesized
      molecules were tested for their RNase A inhibition activities. Gel-based assays
      showed inhibition in micromolar concentrations. The extent of inhibition was
      found to be dependent upon the nature of base as well as the configuration at C-3
      position of catechin.

PMID- 18829316
TI  - Semisynthesis and antitumoral activity of 2-acetylfuranonaphthoquinone and other
      naphthoquinone derivatives from lapachol.
AB  - Ozonolysis of lapachol (1), resulting in an unusual formation of a potent
      antitumor agent 2-acetylfuranonaphthoquinone (3) along with the expected aldehyde
      6, is described. The reaction of lapachol (1) with CAN in dry acetonitrile
      leading to biologically active furanonaphthoquinones is also reported. The
      antitumoral activity of the tested compounds on human DU-145 prostate carcinoma
      cells was evaluated following XTT assay. The results revealed that 2-(1
      methylethenyl)-2,3-dihydronaphtho[2,3-b]furan-4,9-dione (5), beta-lapachone (10)
      and dehydro-beta-lapachone diacetate (11) showed 100% inhibition at 25 microg/ml.
      All the tested samples showed dose-dependent activity.

PMID- 18829317
TI  - Design and synthesis of sulfoximine based inhibitors for HIV-1 protease.
AB  - A new class of potent sulfoximine inhibitors for HIV-1 protease has been designed
      and synthesized. Substitution of the sulfoximine moiety into different parent
      compounds yields different inhibition effects. While our previously studied
      sulfoximine-based inhibitors display potency of 2.5 nM (IC(50)) against HIV-1
      protease, introduction of the sulfoximine moiety into the asymmetric Indinavir
      yielded only micromolar inhibition. Docking studies showed structural variations
      in their modes of binding which explains this unexpected observation. The
      implication of these observations in the development of other sulfoximine
      inhibitors is discussed.

PMID- 18829318
TI  - Vacuum-assisted excision of breast lesions of uncertain malignant potential (B3) 
      an alternative to surgery in selected cases.
AB  - To assess whether vacuum-assisted excision (VAE) is a safe alternative to surgery
      in the treatment of breast lesions of uncertain malignant potential (B3) in which
      no atypia is present on needle core biopsy (NCB). Forty two VAE procedures were
      performed for B3 lesions. Twenty four (57%) were papillary lesions. Eighteen
      (43%) were radial scars. Two patients (4.7%) were upgraded to carcinoma at VAE.
      Two patients with papillary lesions went on to develop cancer in the same breast
      (at 24 and 41 months post VAE). No cancer developed in the radial scar group.
      Eight patients (19%) had surgery - four for carcinoma, two for radial scars
      missed at VAE excision and two for symptomatic papillomatosis. Follow-up
      mammography after VAE of radial scars often showed residual distortion. VAE can
      be a safe alternative to surgery in the treatment of B3 lesions without atypia,
      providing thorough multidisciplinary discussion has taken place.

PMID- 18829319
TI  - Physiological and perceptual responses to backward and forward treadmill walking
      in water.
AB  - We compared physiological and perceptual responses, and stride characteristics
      while walking backward in water with those of walking forward in water. Eight
      males walked on an underwater treadmill, immersed to their xiphoid process level.
      Oxygen uptake ((.)V(O2)), respiratory exchange ratio (R), heart rate (HR), minute
      ventilation ((.)V(E)), blood lactate concentration (BLa), ratings of perceived
      exertion (RPE: for breathing and legs, RPE-Br and RPE-Legs, respectively), blood
      pressure (for systolic and diastolic pressures, SBP and DBP, respectively), and
      step frequency (SF) were measured. In addition, step length (SL) was calculated.
      (.)V(O2), R, HR, V (E), BLa, RPE-Br, RPE-Legs, and SBP were significantly higher
      while walking backward in water than when walking forward in water (P<0.05).
      Furthermore, SF was significantly higher (P<0.001) and SL was significantly lower
      (P<0.001) while walking backward in water, compared to walking forward in water.
      These results indicate that walking backward in water elicits higher
      physiological and perceptual responses than those produced when walking forward
      in water at the same speed.

PMID- 18829320
TI  - Effects of conflicting constraints and age on strategy choice in stepping down
      during gait.
AB  - For negotiating a step down during gait, as in stepping from a curb, two
      different strategies can be used, i.e. heel landing and toe landing. Toe landing
      allows more negative work by the leading leg to reduce the momentum gained during
      the descent, which facilitates maintaining stability but reduces walking
      velocity. We therefore hypothesized that subjects would use a toe landing less
      frequently when instructed to walk faster and when negotiating smaller height
      differences. Furthermore, expecting that older adults would prioritize stability
      over maintaining gait velocity, we hypothesized that they would use toe landing
      more frequently than young adults. Two groups (young: 23+/-1 years, n=8; old:
      73+/-5 years, n=17) walked over a 10-m walkway at 3-5 km/h to step down a single
      step of 5-15 cm halfway. In both groups, toe landing was used less frequently for
      lower steps and less frequently at higher velocities. Older participants used toe
      landing more frequently and more consistently than young participants. This
      preference for toe landing is suggested to reflect adaptive behavior to enhance
      gait stability, rather than an inability to use a heel landing.

PMID- 18829321
TI  - Differences in gait complexity and variability between children with and without
      developmental coordination disorder.
AB  - We used elliptical Fourier analysis (EFA) to examine potential differences in the
      complexity and variability of gait of children with (N=10) and without (N=10)
      Developmental Coordination Disorder (DCD). Children with DCD generated movement
      patters with larger variability and complexity than typically developing (TD)
      children. In addition, children with DCD exhibited greater asymmetry in their
      movement patterns compared to TD children. Our results suggest that children with
      DCD have significantly greater difficulty producing consistent movement patterns
      both across their left and right legs and over repeated strides. EFA techniques
      show promise for distinguishing between different groups of individuals.

PMID- 18829322
TI  - Kinematic assessment of paediatric forefoot varus.
AB  - Forefoot varus is a static deformity not easy to assess clinically. If left
      uncorrected, it is thought to affect both the posture of the patient and the
      kinematics of their lower limbs, and even the spine. Three-dimensional gait
      assessment could help to confirm forefoot varus diagnosis and provide objective
      evidence of the functional adaptive mechanisms postulated in the literature. The
      recently available Oxford Foot Model was used, simultaneously with a conventional
      lower limb model, to compare the kinematics of 10 forefoot varus children (aged 8
      13) and 11 healthy controls (aged 7-13) during gait. Data acquisition was
      performed using a six-camera motion capture system, with a total of 27 reflective
      markers. A patient-by-patient comparison with the controls suggested several
      compensation patterns, although statistically significant differences were found
      only for the mean values of hip adduction/abduction during load response and
      midstance and hip flexion/extension during pre-swing. A multivariate statistical
      technique was used to determine which of the measured variables better separated
      both groups. The best discriminant model presented here includes hip
      adduction/abduction during load response, hindfoot/tibia inversion/eversion
      during pre-swing, hindfoot/tibia dorsiflexion/plantar flexion during load
      response and arch height during midstance, providing a rate of correct
      classification of 81%. The results could not fully confirm the kinematic
      relationships suggested in the literature. The small degree of forefoot varus
      deformity present in the patient group could have prevented other variables from
      becoming discriminant. A larger patient sample would help determine the possible
      different compensatory patterns to different degrees of forefoot varus.

PMID- 18829323
TI  - Time to remove the model organism blinkers.

PMID- 18829324
TI  - Pancreatic adenocarcinoma metastatic to the pineal gland.
AB  - Metastases to the pineal gland are rare and reported cases have consisted
      primarily of gastrointestinal and lung primary malignancies. Here we present the
      case of a 66-year-old female with autosomal dominant polycystic kidney and liver
      disease who was found at autopsy to have an unrecognized infiltrating ductal
      adenocarcinoma of the pancreas with metastases to the liver, lungs and pineal
      gland. As far as we are aware, this is the first report of a metastasis of
      infiltrating ductal adenocarcinoma of the pancreas to the pineal gland.

PMID- 18829325
TI  - Low back pain in neurosurgical outpatients: an audit.
AB  - Low back pain is a common condition. This is a retrospective study of new
      referrals to neurosurgical outpatients at the Western Hospital, Victoria,
      Australia. Two hundred and fifteen histories were systematically reviewed.
      Statistical analysis was performed using univariate and multivariate analyses.
      Patients who had tried physiotherapy, epidural injection or had no pre-outpatient
      imaging were more likely to get MRI (p<0.02). Patients with clinical features of
      neurogenic claudication (p<0.01) or with neurological signs (p=0.02) were more
      likely to proceed to surgery. CT scan demonstrated significant correlation to MRI
      for lumbar canal stenosis, disc disease or the absence of disease (p<0.01).
      Referral guidelines for general practitioners regarding back pain are proposed.
      Recommendations are also made to facilitate the selected use of CT scan and MRI.

PMID- 18829326
TI  - Intraventricular ganglioglioma.
AB  - Gangliogliomas are mixed tumors consisting of both glial elements and
      differentiated neurons. Although any part of the central nervous system can be
      affected, little is known about intraventricular gangliogliomas. A patient with a
      ganglioglioma is presented in the previously unreported location of the anterior
      third ventricle at the foramen of Monro, mimicking a colloid cyst. We review all
      other reported cases of intraventricular ganglioglioma (n=6) to characterize this
      entity. Intraventricular gangliogliomas typically affect younger patients with
      female predominance (male:female, 2:5; median age 25 years). Symptoms occur
      secondary to obstruction of physiological cerebrospinal fluid circulation.
      Complete surgical resection with re-establishment of cerebrospinal fluid drainage
      is the goal of treatment.

PMID- 18829327
TI  - Wernicke's encephalopathy mimicking variant Creutzfeldt-Jakob disease.
AB  - A 45-year-old man from tropical Australia was admitted with subacute social
      withdrawal, cognitive deterioration, reduced awareness and eventual mutism.
      Variant Creutzfeldt-Jakob disease was considered on the basis of WHO case
      definition criteria including typical clinical features and MRI showing
      symmetrical hyperintensity in the pulvinar (posterior) nuclei of the thalami.
      However, tonsillar biopsy was negative. Wernicke's encephalopathy was established
      on the basis of low serum thiamine on admission and eventual clinical improvement
      on high-dose intravenous thiamine replacement, despite initial failure to respond
      to the standard dose of 100 mg daily intramuscularly.

PMID- 18829328
TI  - Can radiation induce pituitary tumors? Giant prolactinoma after radiation
      exposure.
AB  - Radiation is a well-known etiology for many CNS tumors, including meningiomas,
      sarcomas and gliomas. However, occurrence of pituitary adenoma after radiation
      exposure is rare. We report a 21-year-old man with a pituitary adenoma, who was
      treated with post-operative radiotherapy for pontine glioma at 6 years of age.
      The role of radiation exposure in the etiology of pituitary adenoma is discussed,
      along with a literature review of radiation-induced tumors.

PMID- 18829329
TI  - A new Aven-ue to DNA-damage checkpoints.
AB  - Cells frequently arrest or die in response to DNA damage to reduce the likelihood
      of progression to malignancy. A recent study sheds new light on the Aven protein,
      a known apoptotic regulator. After DNA damage, Aven induces cell-cycle arrest via
      ataxia-telangiectasia-mutated (ATM) kinase activation. These findings add Aven to
      a growing list of apopototic regulators that function as double agents in the DNA
      damage response.

PMID- 18829330
TI  - Axial chirality and affinity at the GABA(A) receptor of pyrimido[1,2
      a][1,4]benzodiazepines and related compounds.
AB  - The pyrimido[1,2-a][1,4]benzodiazepines (1a-c) and the 8-membered analogues
      (diazocines 2a and 2b) were separated into their atropisomers with HPLC on a
      chiral column. High stereochemical stability was observed in the atropisomer of
      the 8-membered derivatives (2a and 2b), and the 1,4-benzodiazepine (1c) with 2'
      chloro at the pendant phenyl showed a lower energy barrier for the conversion
      between the atropisomers compared with that with the unsubstituted pendant phenyl
      (1a). The aR isomer of 1a-c was revealed to be the eutomer in GABA(A) receptor
      binding, and the eutomer 1c-R showed extremely potent activity with an IC(50)
      value of 1.5 nM.

PMID- 18829331
TI  - Anti-inflammatory activities of furanoditerpenoids and other constituents from
      Fibraurea tinctoria.
AB  - Five new furanoditerpenoids, epi-8-hydroxycolumbin (1), fibaruretin B (2), C (3),
      E (5), and F (6), were isolated from the stems of Fibraurea tinctoria, as well as
      fibaruretin D (4) from the natural source for the first time, and 39 known
      compounds. The structures (1-6) were elucidated on the basis of spectroscopic
      analysis. All the isolated furanoditerpenoids (1-16) were examined for their in
      vitro activity and some were in vivo anti-inflammatory activity. Compounds 8 and
      9 showed significant anti-inflammatory action administered at a dose of 100mg/kg
      of reducing carrageenan mice paw edema, whereas compound 7, 9, 10, 14, and 16
      were more potent to inhibit NO production. The inhibitory effects of these
      compounds are dose-dependent (1-4 microg/ml).

PMID- 18829332
TI  - 5-Alkyl-2-ferrocenyl-6,7-dihydropyrazolo[1,5-a]pyrazin-4(5H)-one derivatives
      inhibit growth of lung cancer A549 cell by inducing apoptosis.
AB  - we found that 5-alkyl-2-ferrocenyl-6,7-dihydropyrazolo[1,5-a]pyrazin-4(5H)-one
      derivatives 8d, 8e and 8f could effectively induce apoptosis in A549 lung cancer
      cells and elevate the levels of integrin beta4 and ROS. The data suggested that
      these compounds might be promising agents for the cancer therapy, and these
      compounds would be useful tools for further investigate the functions of integrin
      beta4 in regulation of the cancer cell apoptosis.

PMID- 18829333
TI  - Design, synthesis, and structure-activity relationship of novel opioid kappa
      agonists.
AB  - By focusing on 4,5-epoxymorphinan, a traditional opioid skeleton but a new
      structure in the opioid kappa-agonist research field, and by rationally applying
      the 'message-address concept' and 'accessory site hypothesis,' we discovered a
      new chemical class opioid kappa-agonist, TRK-820 (1). Its development as an
      antipruritus is now in the final stage. Here, the full scope of its design,
      synthesis, and structure-activity relationship are described.

PMID- 18829335
TI  - Evaluation of ligand-binding affinity using polynomial empirical scoring
      functions.
AB  - Assessing protein-ligand interaction is of great importance for virtual screening
      initiatives in order to discover new drugs. The present work describes a set of
      empirical scoring functions to assess the binding affinity, involving terms for
      intermolecular hydrogen bonds and contact surface. The results show that our
      methodology works better to predict protein-ligand affinity when compared with
      XSCORE, a popular empirical scoring function.

PMID- 18829334
TI  - Synthesis of N-substituted 5-[2-(N
      alkylamino)ethyl]dibenzo[c,h][1,6]naphthyridines as novel topoisomerase I
      targeting antitumor agents.
AB  - Several N-alkyl and N,N-dialkyl 5H-8,9-dimethoxy-5-(2-aminoethyl)-2,3
      methylenedioxydibenzo[c,h][1,6]naphthyridin-6-ones have been identified as
      topoisomerase I-targeting agents with potent antitumor activity. In the present
      study, the impact on biological activity of substitution of a trifluoromethyl,
      cyano, aminocarbonyl, or ethynyl group on a N-methyl substituent of N,N-dimethyl
      , N-methyl-N-ethyl-, and N-methyl-N-isopropyl 5H-8,9-dimethoxy-5-(2-aminoethyl)
      2,3-methylenedioxydibenzo[c,h][1,6]naphthyridin-6-ones was assessed.

PMID- 18829336
TI  - Application of the sum-peak method to activity standardizations of extended 60Co
      sources.
AB  - The sum-peak method was successfully applied to the determination of the activity
      of extended (60)Co sources measured on a HPGe detector. Monte Carlo simulations
      were used to account for the effects of the spatial variation of the efficiency
      across the sample volume and for the angular correlations between the emitted
      gamma rays. The determined activities agree with the reference values within a
      range of 1.0%.

PMID- 18829337
TI  - Left ventricular outflow tract obstruction after arterial switch operation.
AB  - OBJECTIVE: Postoperative left ventricular outflow tract obstruction (LVOTO) after
      arterial switch operation (ASO) is rare. In this retrospective study, we reviewed
      the cases of 10 patients with LVOTOs post-ASO and analyzed the options used for
      the LVOTOs corrections and the patients' outcomes. METHODS: From December 1982 to
      December 2006, 1689 consecutive ASO were performed. Ten patients presented with
      postoperative LVOTOs (0.59% of all ASO and 7.62% of ASO for Taussig-Bing anomaly
      (TBA)) leading to reoperations. Before ASO they presented with significant
      subaortic gradients (n=4) or predisposing anatomical features (n=9) such as:
      conal septum malalignment (7/9), abnormal tricuspid cords insertions (4/9),
      muscular bundle hypertrophy (3/9) and mitral accessory tissue (2/9). RESULTS: No
      patient was lost in the follow-up: 117+/-33 months. Subaortic gradients had
      developed between 5 months and 14 years after ASO (mean 41+/-35 months) leading
      to reoperations. Most LVOTOs post-ASO were due to fibrotic membranes or fibro
      muscular hypertrophy, removed at first reoperation. After their first
      reoperations, seven patients (70%) had non-significant or low gradients and were
      not reoperated for LVOTO. Three patients underwent iterative surgical procedures
      for LVOTOs leading to two aortic valve replacements associated with LVOTO release
      or Konno procedure. CONCLUSION: Postoperative LVOTO after ASO is rare but happens
      more frequently in TBA. Most of them can benefit from resections of subaortic
      obstacles or septal plasties. In more complex cases iterative surgical procedures
      may lead to complications such as block or severe aortic valve regurgitation.

PMID- 18829338
TI  - Survival after resection of synchronous bilateral lung cancer.
AB  - OBJECTIVE: Due to recent advances in imaging, the incidence of patients
      presenting with bilateral lung lesions is increasing. A single contralateral lung
      lesion can be an isolated metastasis or a synchronous second primary lung cancer.
      For the revision of the TNM in 2009, the International Association for the Study
      of Lung Cancer Staging Committee proposes that patients with contralateral lung
      nodules remain classified as M1 disease. In this retrospective study, the
      survival after resection of synchronous bilateral lung cancer is evaluated.
      METHODS: From our database of bronchial carcinoma, all patients with bilateral
      synchronous lung lesions between 1990 and 2007 were retrieved. We analysed 57
      patients in which, after functional assessment and thorough staging, the decision
      was taken to treat the disease with bilateral resection. All these files were
      retrospectively reviewed. Twenty-one patients were excluded from this analysis
      because only one side was resected (n=15) or one of the lesions was non
      neoplastic on final pathology (n=6). RESULTS: Thirty-six patients underwent
      bilateral resection for synchronous multiple primary lung cancer. All resections
      were performed as sequential procedures. In 23 patients, one side was
      anatomically resected (2 pneumonectomies) and the contralateral side was resected
      by limited resection. In 10 patients a bilateral lobectomy was performed, and 3
      patients had bilateral limited resections. Postoperative mortality was 2.8%.
      Eighteen patients had a tumour with a different histological pattern, confirmed
      by comparing both specimens by an experienced senior pathologist. The median
      survival after resection of synchronous bilateral lung cancer in our series was
      25.4 months with a 5-year survival rate of 38%. There was no significant
      difference in survival between patients with different versus same histology.
      This survival is much higher compared to the survival of assumed stage IV
      disease. CONCLUSIONS: Our study shows that selected patients with bilateral lung
      cancer may benefit from an aggressive approach, with acceptable morbidity and
      mortality, and rewarding long-term survival. Patients with a single contralateral
      lung lesion should not be treated as disseminated disease (stage IV). After
      extensive searching for metastatic spread, bilateral surgical resection should be
      considered in fit patients.

PMID- 18829339
TI  - Reduced pulmonary inflammatory response during cardiopulmonary bypass: effects of
      combined pulmonary perfusion and carbon monoxide inhalation.
AB  - OBJECTIVE: Pulmonary inflammation induced by cardiopulmonary bypass (CPB) is one
      of the main causes for lung injury after cardiac surgery. Pulmonary perfusions as
      well as carbon monoxide (CO) inhalation are known to reduce the inflammatory
      reaction of the lung. We hypothesized that a combination of pulmonary perfusion
      and carbon monoxide inhalation leads to an even stronger reduction of the lung
      inflammation. METHODS: Pigs (n=7 per experimental group) were randomized to sham
      operation (SHAM), conventional CPB (CPB), inhalation of CO (CPB+CO, 250 ppm),
      pulmonary perfusion (CPB+PP) or pulmonary perfusion plus inhalation of CO
      (CPB+PP+CO). Various cytokine levels (TNF-alpha, IL-1, IL-6, and IL-10) and
      caspase-3 activity were measured using enzyme-linked immunosorbent assay (ELISA).
      Transcription factor activity was analyzed via electrophoretic mobility shift
      assay (EMSA). Blood gases and hemodynamics were measured continuously. A p value
      <0.05 assessed by Holm-Sidak method was considered statistically significant.
      RESULTS: Hemodynamic parameters and blood gas analysis showed no significant
      differences between the groups. While IL-1 protein expression was comparable
      between the groups, TNF-alpha (478+/-58 vs 869+/-95 pg/ml; p<0.001) and IL-6
      protein levels in the lung (256+/-82 vs 936+/-76 pg/ml; p<0.001) showed a
      significant inhibition in the CPB+PP+CO group at 120 min post-bypass time
      compared to the CPB group. The cytokine levels were comparable to the CPB+PP and
      CPB+CO group. IL-10 protein expression (325+/-47 vs 65+/-27 pg/ml; p<0.05) was
      significantly higher in the CO-treated compared to CPB+PP and CPB-treated animals
      at 120 min post-bypass. Activation of the transcription factors NF-kappaB and AP
      1 showed a CO-mediated induction compared to the CPB or CPB+PP group. Caspase-3
      activity revealed a CO-dependent, significant inhibition in CO and CPB+PP+CO
      treated animals compared to CPB animals (p<0.05). CONCLUSION: The combination of
      pulmonary perfusion and inhalative carbon monoxide inhibits CPB-mediated
      pulmonary inflammation as well as pulmonary apoptosis stronger than pulmonary
      perfusion or carbon monoxide alone.

PMID- 18829340
TI  - Thoracic endovascular aortic repair: impact of urgency on outcome and quality of
      life.
AB  - OBJECTIVES: Endovascular repair of the descending thoracic aorta is a very
      promising technique in elective and, particularly, emergency situations. This
      study assessed the impact of urgency of the procedure on outcome and mid-term
      quality of life in surviving patients. METHODS: Post hoc analysis of
      prospectively collected data of 58 consecutive patients (January 2001-December
      2005) with surgical pathologies of the descending thoracic aorta treated by
      endovascular means. Six patients were excluded due to recent operations on the
      ascending aorta before thoracic endovascular repair. The remaining patients
      (n=52) were 69+/-10 years old, and 43 were men (83%). Twenty-seven had been
      treated electively, and 25 for emergency indications. Reasons for emergency were
      acute type B aortic dissections with or without malperfusion syndrome in 14, and
      aortic ruptures in 11 cases. Follow-up was 29+/-16 months. Endpoints were
      perioperative and late morbidity and mortality rates and long-term quality of
      life as assessed by the short form health survey (SF-36) and Hospital Anxiety and
      Depression Scale questionnaires. RESULTS: Cohorts were comparable regarding age,
      sex, cardiovascular risk factors, and comorbidities. Perioperative mortality was
      somewhat higher in emergency cases (12% vs 4%, p=0.34). Paraplegia occurred in
      one patient in each cohort (4%). Overall quality of life after two and a half
      years was similar in both treatment cohorts: 72 (58-124) after emergency, and 85
      (61-105) after elective endovascular aortic repair (p=0.98). Normal scores range
      from 85 to 115. Anxiety and depression scores were in the normal range and
      comparable. CONCLUSIONS: Thoracic endovascular aortic repair is an excellent and
      safe treatment option for the diseased descending aorta, particularly in
      emergency situations. Early morbidity and mortality rates can be kept very low.
      Mid-term quality of life was not affected by the urgency of the procedure.
      Similarly, mid-term anxiety and depression scores were not increased after
      emergency situations.

PMID- 18829341
TI  - Effect of coronary artery bypass surgery on myocardial function as assessed by
      tissue Doppler echocardiography.
AB  - OBJECTIVE: Coronary artery bypass graft (CABG) surgery may induce myocardial
      stunning and thereby affect cardiac function. We aimed to assess whether
      myocardial function is affected by CABG in patients with preserved preoperative
      systolic function. METHODS: Myocardial tissue peak velocities were recorded at
      the lateral and septal angle of the mitral annulus as well as at the lateral
      tricuspid annulus by pulsed wave tissue Doppler echocardiography before cardiac
      surgery, and then at 5 days, 6 weeks and 18 months after surgery. RESULTS: Thirty
      two consecutive patients with preserved systolic left ventricular function (31
      male, 63+/-10 years) undergoing CABG (9 with cardiopulmonary bypass on-pump, 23
      beating heart off-pump) were included. Peak systolic velocity on tissue Doppler
      echocardiography was unchanged after surgery. In contrast, peak early diastolic
      velocities (E') improved significantly 5 days and 6 weeks after surgery in the
      septal area (6.2+/-2.3 to 7.4+/-2.6 and 7.6+/-2.6 cm/s, respectively; p<0.05) and
      at the left ventricular lateral wall (9.1+/-3.0 to 10.1+/-3.0 and 11.3+/-2.9
      cm/s, respectively; p<0.05), and then declined slowly to preoperative values
      after 18 months. In contrast, right ventricular E' decreased significantly
      immediately after surgery (9.8+/-2.7 preoperatively to 7.7+/-1.7 cm/s at 5 days,
      p=0.005) with only incomplete recovery over time. This was similar in both the
      conventional and the off-pump CABG cohort. CONCLUSIONS: Left ventricular function
      did not deteriorate after CABG in patients with preserved preoperative systolic
      function. On the contrary, diastolic function improved immediately after CABG.
      Right ventricular function, in contrast, appeared to be damaged by surgery, to
      similar degrees regardless of whether patients underwent off-pump or on-pump
      surgery. Hypothermia and immune-inflammatory activation are, therefore, not
      plausible explanations for this decline in right ventricular function.

PMID- 18829342
TI  - Infective endocarditis in children: native valve preservation is frequently
      possible despite advanced clinical disease.
AB  - BACKGROUND: Recent reports describing surgical experiences with childhood IE are
      sparse. We sought to determine patient-specific characteristics and their impact
      on outcome for children with infective endocarditis (IE) undergoing surgical
      intervention. We therefore reviewed all cases of culture-proven IE referred for
      surgical intervention at our institution over the last three decades. METHODS: Of
      15,124 cardiovascular surgical procedures performed between 1978 and 2007 at our
      institution on children under the age of 18, only 30 (0.2%) were undertaken for a
      primary diagnosis of IE. All 30 children underwent chart review and retrospective
      risk-hazard analysis. RESULTS: Median patient age was 9.8 years (range 10 weeks
      to 17.5 years). Underlying congenital cardiac lesions were present in 22 (77%)
      and previous intra-cardiac repair in 9 (30%). Septic emboli occurred in 13 (46%),
      causing permanent strokes in 4 (14%). Streptococcus viridans and Staphylococcus
      aureus were the predominant organisms. S. viridans was associated with underlying
      congenital lesions (p<0.01). S. aureus was associated with abscess formation
      (p<0.03), clinical sepsis (p<0.04), acute deterioration (p<0.01), prolonged
      hospitalization (p<0.01) and death (p<0.01). Aortic, mitral and tricuspid valves
      were involved with equal frequency, more than the right ventricular outflow
      tract. Two valves were involved in 30%. The native valve was preserved at
      operation in 22 (73% cases). Univariate predictors for valve replacement included
      increased leaflet thickening (p<0.01) and occurrence of septic embolization
      (p=0.02), whereas moderate/severe valvular regurgitation was not significant.
      Five-year freedom from IE-related death and re-intervention was 84% and 80%,
      respectively. At latest follow-up 96% of patients are NHYA I. CONCLUSIONS:
      Children undergoing surgery for infective endocarditis frequently have advanced
      disease with embolic complications and double valve involvement. However,
      preservation of the native valve is frequently possible. Need for valve
      replacement is suggested by leaflet thickening and embolization. Despite the
      advanced pathology, survival and functional outcomes are favorable.

PMID- 18829343
TI  - Minimally invasive mitral valve surgery: a systematic review and meta-analysis.
AB  - The mitral valve has been traditionally approached through a median sternotomy.
      However, significant advances in surgical optics, instrumentation, tissue
      telemanipulation, and perfusion technology have allowed for mitral valve surgery
      to be performed using progressively smaller incisions including the
      minithoracotomy and hemisternotomy. Due to reports of excellent results,
      minimally invasive mitral valve surgery has become a standard of care at certain
      specialized centers worldwide. This meta-analysis quantifies the effects of
      minimally invasive mitral valve surgery on morbidity and mortality compared with
      conventional mitral surgery and demonstrates equivalent perioperative mortality
      (1641 patients, odds ratio (OR) 0.46, 95% confidence interval 0.15-1.42, p=0.18),
      reduced need for reoperation for bleeding (1553 patients, OR 0.56, 95% CI 0.35
      0.90, p=0.02) and a trend towards shorter hospital stays (350 patients, weighted
      mean difference (WMD) -0.73, 95% CI -1.52 to 0.05, p=0.07). These benefits were
      evident despite longer cardiopulmonary bypass (WMD 25.81, 95% CI 13.13-38.50,
      p<0.0001) and cross-clamp times (WMD 20.91, 95% CI 8.79-33.04, p=0.0007) in the
      minimally invasive group. Case-control studies show consistently less pain and
      faster recovery compared to those having a conventional approach. Data for
      minimally invasive mitral valve surgery after previous cardiac surgery are
      limited but consistently demonstrate reduced blood loss, fewer transfusions and
      faster recovery compared to reoperative sternotomy. Long-term follow-up data from
      multiple cohort studies are also examined revealing equivalent survival and
      freedom from reoperation. Thus, current clinical data suggest that minimally
      invasive mitral valve surgery is a safe and a durable alternative to a
      conventional approach and is associated with less morbidity.

PMID- 18829344
TI  - Systemic treatment of gastric cancer.
AB  - Treatment of gastric cancer is improved over the past years, but unanswered
      questions remain regarding the efficacy of systemic treatments in adjuvant,
      neoadjuvant and metastatic setting. It has not been definitively demonstrated the
      efficacy of adjuvant chemotherapy, that should not be adopted as a standard
      approach to localized gastric cancer. On the contrary, compelling evidence in
      support of perioperative chemotherapy with ECF regimen has been recently provided
      by the MAGIC trial, although many criticisms have been moved to this study. For
      metastatic setting, a recent meta-analysis showed a small, but significant
      survival benefit for combination vs single agent chemotherapy, and the V-325
      trial demonstrated the superiority of a docetaxel containing regimen (DCF) over a
      doublet (CF). Finally, the results of ongoing clinical trials on a number of new
      molecular-targeted drugs should confirm their role in gastric cancer.

PMID- 18829346
TI  - Comparison of hamstring neuromechanical properties between healthy males and
      females and the influence of musculotendinous stiffness.
AB  - The hamstrings limit anterior cruciate ligament (ACL) loading, and neuromuscular
      control of these muscles is crucial for dynamic knee joint stability. Sex
      differences in electromechanical delay (EMD) and rate of force production (RFP)
      have been reported previously, and attributed to differences in musculotendinous
      stiffness (MTS). These characteristics define the neuromechanical response to
      joint perturbation, and sex differences in these characteristics may contribute
      to the greater female ACL injury risk. However, it is unclear if these
      differences exist in the hamstrings, and the relationship between MTS and
      neuromechanical function has not been assessed directly. Hamstring MTS, EMD, the
      time required to produce 50% peak force (Time50%), and RFP were assessed in 20
      males and 20 females with no history of ACL injury. EMD did not differ
      significantly across sex (p=0.788). However, MTS (p<0.001) and RFP (p=0.003) were
      greater in males, Time50% (p=0.013) was shorter in males, and Time50% was
      negatively correlated with MTS (r=-0.332, p=0.039). These results suggest that
      neuromechanical hamstring function in females may limit dynamic knee joint
      stability, potentially contributing to the greater female ACL injury risk.
      However, future research is necessary to determine the direct influences of MTS
      and neuromechanical function on dynamic knee joint stability and ACL injury risk.

PMID- 18829347
TI  - Surface EMG: the issue of electrode location.
AB  - This paper contributes to clarifying the conditions under which electrode
      position for surface EMG detection is critical and leads to estimates of EMG
      variables that are different from those obtained in other nearby locations.
      Whereas a number of previous works outline the need to avoid the innervation zone
      (or the muscle belly), many authors place electrodes in the central part or bulge
      of the muscle of interest where the innervation zone is likely to be. Computer
      simulations are presented to explain the effect of the innervation zone on
      amplitude, frequency and conduction velocity estimates from the signal and the
      need to avoid placing electrodes near it. Experimental signals recorded from some
      superficial muscles of the limbs and trunk (abductor pollicis brevis, flexor
      pollicis brevis, biceps, upper trapezius, vastus medialis, vastus lateralis) were
      processed providing support for the findings obtained from simulations. The use
      of multichannel techniques is recommended to estimate the location of the
      innervation zone and to properly choose the optimal position of the detection
      point(s) allowing meaningful estimates of EMG variables during movement analysis.

PMID- 18829348
TI  - Pediatric cubital tunnel syndrome by anconeus epitrochlearis: a case report.

PMID- 18829349
TI  - Four-part valgus impacted proximal humeral fracture presenting three months after
      injury in a young patient: open reduction and internal fixation with triple
      osteotomy and bone graft augmentation.

PMID- 18829350
TI  - Methylation of the OP-1 promoter: potential role in the age-related decline in OP
      1 expression in cartilage.
AB  - OBJECTIVE: An age-related decline in chondrocyte production of osteogenic protein
      1 (OP-1) (Bone Morphogenetic Protein-7) may contribute to cartilage loss in
      osteoarthritis. This study was designed to determine if increased methylation of
      the OP-1 promoter might serve as a mechanism for the age-related decline in OP-1
      expression. METHODS: Human articular chondrocytes were isolated from cartilage
      obtained after death from tissue donors (ages 19-86 years) without a known
      history of arthritis. DNA was obtained from isolated chondrocytes in primary
      culture and analyzed for OP-1 promoter methylation by polymerase chain reaction
      (PCR) after bisulfite treatment. Cultured cells were treated with the DNA
      methyltransferase inhibitor 5-azacytidine and OP-1 production was measured in the
      media by enzyme-linked immunosorbent assay (ELISA). RNA was isolated to measure
      expression of insulin-like growth factor-1 (IGF-1), the IGF-1 receptor (IGF-1R),
      aggrecan, and OP-1 by real-time PCR. RESULTS: Methylation of the OP-1 promoter
      was detected in chondrocytes isolated from tissue obtained from older adults and
      there was a positive correlation between age and OP-1 methylation status (n=22,
      R(2)=0.277, P=0.014). Inhibition of methylation in cultured cells with 5
      azacytidine increased chondrocyte production of OP-1 protein and increased the
      expression of the IGF-1, the IGF-1R, aggrecan, and OP-1 genes but not GAPDH.
      CONCLUSION: Age-related methylation of the OP-1 promoter may contribute to a
      decrease in OP-1 production in cartilage and a decrease in expression of OP-1
      responsive genes such as IGF-1, the IGF-1R, and aggrecan.

PMID- 18829351
TI  - Platelet function in hypertension.
AB  - Platelets from hypertensive patients show increased sensitivity to agonists and
      have high intracellular free Ca(2+) concentration. Furthermore, in hypertension,
      platelets show enhanced endogenous production of reactive oxygen species and a
      reduced antioxidant status which increases protein tyrosine phosphorylation,
      enhances Ca(2+) mobilization and attenuates NO bioavailability. The study of the
      abnormalities in platelet function in hypertensive patients can lead to the
      development of new pharmacological strategies to prevent and/or palliate
      hypertension-derived complications associated to platelet hyperactivity.

PMID- 18829352
TI  - High-density SNP genotyping to define beta-globin locus haplotypes.
AB  - Five major beta-globin locus haplotypes have been established in individuals with
      sickle cell disease (SCD) from the Benin, Bantu, Senegal, Cameroon, and Arab
      Indian populations. Historically, beta-haplotypes were established using
      restriction fragment length polymorphism (RFLP) analysis across the beta-locus,
      which consists of five functional beta-like globin genes located on chromosome
      11. Previous attempts to correlate these haplotypes as robust predictors of
      clinical phenotypes observed in SCD have not been successful. We speculate that
      the coverage and distribution of the RFLP sites located proximal to or within the
      globin genes are not sufficiently dense to accurately reflect the complexity of
      this region. To test our hypothesis, we performed RFLP analysis and high-density
      single nucleotide polymorphism (SNP) genotyping across the beta-locus using DNA
      samples from healthy African Americans with either normal hemoglobin A (HbAA) or
      individuals with homozygous SS (HbSS) disease. Using the genotyping data from 88
      SNPs and Haploview analysis, we generated a greater number of haplotypes than
      that observed with RFLP analysis alone. Furthermore, a unique pattern of long
      range linkage disequilibrium between the locus control region and the beta-like
      globin genes was observed in the HbSS group. Interestingly, we observed multiple
      SNPs within the HindIII restriction site located in the Ggamma-globin intervening
      sequence II which produced the same RFLP pattern. These findings illustrated the
      inability of RFLP analysis to decipher the complexity of sequence variations that
      impacts genomic structure in this region. Our data suggest that high-density SNP
      mapping may be required to accurately define beta-haplotypes that correlate with
      the different clinical phenotypes observed in SCD.

PMID- 18829353
TI  - Alpha-tocopherol protects against oxidative damage to lipids of the rod outer
      segments of the equine retina.
AB  - Oxidative stress is a possible risk factor for eye diseases. Lipid peroxidation
      is one of the major events induced by oxidative stress and is particularly active
      in polyunsaturated fatty acid (PUFA)-rich biomembranes. This work evaluated
      endogenous lipid antioxidants, in vitro non-enzymatic lipid peroxidation of rod
      outer segment membranes (ROS), the fatty acid composition during oxidative damage
      of total lipids from equine retina and ROS, and the protective action of alpha
      tocopherol (alpha-Toc). The major lipid soluble antioxidant was alpha-Toc
      followed by retinoids and carotenoids. The retina contained a high percentage of
      PUFAs, mainly docosahexaenoic acid (22:6n-3) and arachidonic acid (20:4n-6).
      Lipid peroxidation of the equine ROS, induced by Fe(2+)-ascorbate, was monitored
      using chemiluminescence (CL) with or without pre-treatment with alpha-Toc. With
      alpha-Toc pre-treatment, CL values were significantly decreased. The most
      abundant fatty acid was 22:6n-3. After 3h incubation, 95% of total PUFAs were
      destroyed by peroxidation, whereas in alpha-Toc pre-treated ROS the percentage
      was significantly decreased. The results show that the retina has an endogenous
      lipid soluble antioxidant system. ROS were highly sensitive to oxidative damage,
      since their fatty acid composition was markedly modified during the lipid
      peroxidation process. The protective role of alpha-Toc as an antioxidant was
      evident and it could be used in the treatment of equine ocular diseases in which
      free radicals are involved.

PMID- 18829354
TI  - Clinical NOE 13C MRS for neuropsychiatric disorders of the frontal lobe.
AB  - In this communication, a scheme is described whereby in vivo (13)C MRS can safely
      be performed in the frontal lobe, a human brain region hitherto precluded on
      grounds of SAR, but important in being the seat of impaired cognitive function in
      many neuropsychiatric and developmental disorders. By combining two well known
      features of (13)C NMR-the use of low power NOE and the focus on (13)C carbon
      atoms which are only minimally coupled to protons, we are able to overcome the
      obstacle of SAR and develop means of monitoring the (13)C fluxes of critically
      important metabolic pathways in frontal brain structures of normal volunteers and
      patients. Using a combination of low-power WALTZ decoupling, variants of random
      noise for nuclear overhauser effect enhancement it was possible to reduce power
      deposition to 20% of the advised maximum specific absorption rate (SAR). In model
      solutions (13)C signal enhancement achieved with this scheme were comparable to
      that obtained with WALTZ-4. In human brain, the low power procedure effectively
      determined glutamine, glutamate and bicarbonate in the posterior parietal brain
      after [1-(13)C] glucose infusion. The same (13)C enriched metabolites were
      defined in frontal brain of human volunteers after administration of [1-(13)C]
      acetate, a recognized probe of glial metabolism. Time courses of incorporation of
      (13)C into cerebral glutamate, glutamine and bicarbonate were constructed. The
      results suggest efficacy for measurement of in vivo cerebral metabolic rates of
      the glutamate-glutamine and tricarboxylic acid cycles in 20 min MR scans in
      previously inaccessible brain regions in humans at 1.5 T. We predict these will
      be clinically useful biomarkers in many human neuropsychiatric and genetic
      conditions.

PMID- 18829355
TI  - MRS signal quantitation: a review of time- and frequency-domain methods.
AB  - In this paper an overview of time-domain and frequency-domain quantitation
      methods is given. Advantages and drawbacks of these two families of quantitation
      methods are discussed. An overview of preprocessing methods, such as lineshape
      correction methods or unwanted component removal methods, is also given. The
      choice of the quantitation method depends on the data under investigation and the
      pursued objectives.

PMID- 18829356
TI  - Amino acid type identification in NMR spectra of proteins via beta- and gamma
      carbon edited experiments.
AB  - In this work, we introduce a set of pulse sequences that provide amino acid type
      identification of the NH correlation signals of proteins. The first pulse
      sequence is a modification of the CBCA(CO)NH experiment that exploits spin
      coupling topologies to differentiate between amino acid types. A set of eight 2D
      (1)H-(15)N correlation spectra is recorded where the sign of the cross-peaks
      change from one spectrum to another according to the amino acid type of the
      preceding residue in the protein sequence. Linear combination of these eight data
      sets produces four subspectra. Taking also into account the sign of the
      correlation signals, this method allows the classification of the NH signals into
      six different groups, depending on the character of the preceding residue. This
      sequence is complemented with a (CGCBCACO)NH experiment that allows the
      subdivision of the largest of these groups into two smaller ones. Finally, a
      modification of the CBCANH experiment led to a similar classification of NH
      signals into six different groups, but now depending on the type of its own amino
      acid. The set of pulse sequences is demonstrated with two proteins of small to
      moderate size.

PMID- 18829357
TI  - Data mining PubChem using a support vector machine with the Signature molecular
      descriptor: classification of factor XIa inhibitors.
AB  - The amount of high-throughput screening (HTS) data readily available has
      significantly increased because of the PubChem project
      (http://pubchem.ncbi.nlm.nih.gov/). There is considerable opportunity for data
      mining of small molecules for a variety of biological systems using
      cheminformatic tools and the resources available through PubChem. In this work,
      we trained a support vector machine (SVM) classifier using the Signature
      molecular descriptor on factor XIa inhibitor HTS data. The optimal number of
      Signatures was selected by implementing a feature selection algorithm of highly
      correlated clusters. Our method included an improvement that allowed clusters to
      work together for accuracy improvement, where previous methods have scored
      clusters on an individual basis. The resulting model had a 10-fold cross
      validation accuracy of 89%, and additional validation was provided by two
      independent test sets. We applied the SVM to rapidly predict activity for
      approximately 12 million compounds also deposited in PubChem. Confidence in these
      predictions was assessed by considering the number of Signatures within the
      training set range for a given compound, defined as the overlap metric. To
      further evaluate compounds identified as active by the SVM, docking studies were
      performed using AutoDock. A focused database of compounds predicted to be active
      was obtained with several of the compounds appreciably dissimilar to those used
      in training the SVM. This focused database is suitable for further study. The
      data mining technique presented here is not specific to factor XIa inhibitors,
      and could be applied to other bioassays in PubChem where one is looking to expand
      the search for small molecules as chemical probes.

PMID- 18829358
TI  - Virtual screening against Mycobacterium tuberculosis dihydrofolate reductase:
      suggested workflow for compound prioritization using structure interaction
      fingerprints.
AB  - In this study, we suggest a new workflow for the identification and
      prioritization of potential compounds targeted against Mycobacterium tuberculosis
      dihydrofolate reductase, an important folate cycle enzyme and a validated target
      for the development of anti-tubercular agents. First, we have performed an
      integrated pharmacophore and structure-based virtual screening using Maybridge
      small molecule database, subsequently interaction patterns from known actives to
      the receptor were applied for scoring and ranking the virtual screening hits
      using structure interaction fingerprint (SIFt)-based similarity approach. In
      addition, agglomerative hierarchical clustering of the structure interaction
      fingerprints permits the easy separation of active from inactive binding modes.
      Using this approach we screened 59275 Maybridge compounds and 20 compounds were
      prioritized as promising virtual screening hits. Though using a receptor
      interaction scoring approach, the results were not biased toward the chemical
      classes of the known actives and the proposed compounds were structurally diverse
      with low molecular weights and structural complexities. Our results suggest that
      structure-based virtual screening coupled with the SIFt should be a valuable tool
      for prioritization of virtual screening hits.

PMID- 18829359
TI  - Growth hormone deficient patients after traumatic brain injury--baseline
      characteristics and benefits after growth hormone replacement--an analysis of the
      German KIMS database.
AB  - OBJECTIVE: In recent years, traumatic brain injury (TBI) has been identified as a
      significant cause of growth hormone deficiency (GHD). The aim of the present
      study was to characterize adult TBI patients with GHD to elucidate the effect of
      human growth hormone (hGH) replacement in TBI patients as documented in the
      German Pfizer International Metabolic (KIMS) database. DESIGN: As of October
      2006, 84 TBI patients had been included in the German KIMS database (n=28
      childhood-onset and 54 adult-onset GHD). All 84 TBI patients were matched with 84
      patients with GHD due to non-functioning pituitary adenoma (NFPA) also included
      in this database. Analysis of clinical and outcome variables was performed, with
      comparisons of childhood vs. adult TBI, and TBI vs. NFPA patients, at baseline
      and one-year follow-up. RESULTS: TBI patients with GHD were significantly younger
      at the onset of pituitary disease and exhibited a significantly longer time span
      between GHD diagnosis and KIMS entry than NFPA patients. Those KIMS patients who
      had sustained their TBI in childhood were of significantly shorter stature than
      adult-onset TBI patients. At 1-year follow-up, insulin-like growth factor I (IGF
      I) standard deviation score levels had returned to the normal range and quality
      of life (QoL), as measured by QoL- Assessment of Growth Hormone Deficiency in
      Adults (AGHDA) questionnaire, improved significantly in TBI as in NFPA patients.
      CONCLUSION: This analysis provides preliminary data that TBI patients with GHD
      benefit from hGH replacement in terms of improved QoL in a similar fashion as do
      NFPA patients. Moreover, it suggests that belated diagnosis and treatment in
      childhood-onset GHD due to TBI might be related to a shorter final height in
      these children.

PMID- 18829360
TI  - Ethics issues for HIV/AIDS researchers in international settings - perspectives
      from the Canadian experience.
AB  - In recognition of the level of international HIV/AIDS research being conducted by
      Canadians, the Canadian Association for HIV Research (CAHR), along with its
      partners, has developed a resource document to assist researchers in identifying
      and preparing for the unique ethics issues and challenges that may arise during
      international HIV/AIDS research. Between 2004 and 2007, face-to-face
      consultations were undertaken with community and government stakeholders, and
      interviews were conducted with eight prominent HIV/AIDS researchers with
      international experience to identify key research ethics challenges and
      structural, cultural, political, social, and economic factors that may impact
      HIV/AIDS research ethics in resource-limited settings. These challenges and
      factors served as the basis for the hypothetical ethics issues case scenarios
      developed for each of the four research tracks. Ethics issues were identified at
      every stage of the research process. Key contextual issues included: (1) stigma
      and culturally-embedded conceptualizations of HIV; (2) local and global politics
      and economics; (3) gender inequities, power dynamics, and sexual roles; and (4)
      allocation and availability of resources for research and health services. The
      final document resulting from the consultation process provides a framework for
      open dialogue on the complex and interconnected ethics issues researchers may
      experience in the field of international HIV/AIDS research, and contributes to
      the HIV/AIDS research field by reinforcing the need for high quality and
      ethically sound research. This document can be found at http://ethics.cahr
      acrv.ca/.

PMID- 18829361
TI  - Salmonella: the pelvic masquerader.
AB  - Salmonella sp is a significant cause of morbidity and mortality. Although
      commonly infecting the gastrointestinal system, other presentations are not
      unheard of. Salmonella is an unlikely and an unusual cause of genital tract
      infection. We describe a woman with suspected pelvic inflammatory disease
      eventually confirmed as Salmonella O C2 infection.

PMID- 18829362
TI  - A prospective study of quality of life in 77 type 1 diabetic patients 12 months
      after a hospital therapeutic educational programme.
AB  - AIM: The aim of therapeutic education includes improvement of quality of life
      (QOL). However, the majority of studies are focused on biomedical or behavioural
      markers only. We performed a prospective study to assess QOL in adult type 1
      diabetic patients for one year following a hospital educational programme.
      METHODS: During this prospective single-centre study, QOL was assessed by the
      DQOL questionnaire in 77 consecutive patients at baseline and three, six and 12
      months after a three-day educational programme. RESULTS: The rate of response was
      72.7% (n=55) at three months and 67.5% (n=52) at one year. The overall DQOL score
      improved at three months from 65.6+/-10.1 to 70.1+/-10.4 (P<0.001), and at one
      year from 65.1+/-10.4 to 68.5+/-11.7 (P=0.001). Patients exhibited greater
      satisfaction (66.3+/-15 versus 75.3+/-14.1, P<0.001), a diminished impact of
      diabetes (61.2+/-10 versus 63.4+/-9.6, P=0.016) as well as of anxiety related to
      diabetes (67.6+/-18.6 versus 73.6+/-16.2, P=0.009) at three months. This
      significant improvement was maintained at one year. Improvement in DQOL score at
      three months was positively correlated with a reduction in HbA(1c) (7.6+/-1.4%
      versus 7.8+/-1.4%, P=0.032), (r=-0.293, P<0.037). Patients with serious
      hypoglycaemia before the programme appeared to derive greater benefit from
      therapeutic education (OR: 9.88, 95% CI: 1.094-89.20). CONCLUSION: QOL assessed
      by DQOL improved after therapeutic education and during the following year. The
      improvement in DQOL score at three months correlated with a reduction in HbA(1c)
      levels and appeared to particularly benefit to those who had severe hypoglycaemia
      before the programme.

PMID- 18829363
TI  - Fulminant type 1 diabetes in Caucasians: A report of three cases.
AB  - CONTEXT: Fulminant type 1 diabetes is a new clinical entity in which the process
      of beta-cell destruction, and the subsequent progression of hyperglycaemia and
      ketoacidosis, are extremely rapid. Until now, this subtype of type 1 diabetes has
      only been reported in the Asian population, especially Japanese and Koreans.
      CASES: We report here on three cases of fulminant type 1 diabetes in Caucasian
      French women. Both the clinical and biological characteristics of these patients
      are similar to those reported in Japanese studies. Notably, all patients
      experienced severe ketoacidosis (pH<7.1) that occurred abruptly after the onset
      of hyperglycaemic symptoms (<6 days), with near-normal HbA(1c) values at
      diagnosis (5.6, 6.4 and 6.8%). Patients were treated in the intensive care unit
      with basal-bolus insulin therapy with no remission of their diabetes; pancreatic
      islet-related autoantibodies were all negative. Fasting C-peptide levels were
      undetectable, suggesting complete destruction of pancreatic beta-cells. HLA
      phenotyping of these Caucasian patients did not find the specific HLA haplotype
      (DRB1*0405-DQB1*0401) previously found to be linked to fulminant type 1 diabetes
      in Japanese patients. CONCLUSION: These are the first cases of fulminant type 1
      diabetes reported in Caucasians. These cases reveal new perspectives as regards
      the worldwide distribution of this intriguing clinical entity.

PMID- 18829364
TI  - The metabolic syndrome, diabetes and lung dysfunction.
AB  - Sleep-disordered breathing and sleep apnoea are conditions frequently associated
      with comorbidity, including obesity, diabetes, hypertension, insulin resistance
      (metabolic syndrome) and cardiovascular disease. The diabetic state (type 1 and
      type 2 diabetes) may be associated to diminished lung function and, in
      particular, decreased vital capacity, and the association between chronic
      obstructive pulmonary disease (COPD) and type 2 diabetes may be due to a shared
      inflammatory process. Also, the alteration in circulating endothelial progenitor
      cells found in respiratory disease, the metabolic syndrome and cardiovascular
      disease reflect a common condition of endothelial dysfunction.

PMID- 18829365
TI  - [Permanent implant prostate cancer brachytherapy].
AB  - With an experience of more than 20 years for the pionneers (and more than 10
      years in France), permanent implant brachytherapy using Iodin 125 seeds is now
      recognized as a valuable alternative therapy for localized low-risk prostate
      cancer patients. An extension of the indications of exclusive brachytherapy
      towards selected patients in the intermediate-risk group is presently under
      study. Moreover, for patients in the high-risk group, brachytherapy, as an
      addition to external radiotherapy, could represent one of the best way to
      escalate the dose for some patients. Various permanent implant brachytherapy
      techniques have been proposed; preplanning or real-time techniques, loose seeds
      or stranded seeds, manual or automatic injection of the seeds. The main point
      here is the ability to perfectly master the procedure and to comply with the
      dosimetric constraints which have been recently redefined by the Groupe europeen
      de curietherapie--European Society for Therapeutic Radiology and Oncology (GEC
      ESTRO) group. Mid- and long-term results which are now available in the
      literature indicate relapse-free survival of about 90% at 5-10 years, the best
      results being obtained with satisfactory dosimetric data. Some comparative data
      have shown that the incontinence and impotence rates after brachytherapy seemed
      to be significantly inferior to what is currently observed after surgery.
      However, a risk of about 3-5% of urinary retention is usually reported after
      brachytherapy, as well as an irritative urinary syndrome which may be significant
      and last several months. In spite of those drawbacks, with excellent long-term
      results and low rates of incontinence and impotence, brachytherapy can be
      expected to be proposed to an increasing number of patients in France in the next
      future.

PMID- 18829366
TI  - [Perspectives in diagnosis and management of malignant gliomas].
AB  - The goal of this review is to briefly present the main recent advances of
      research in malignant gliomas and to consider future developments, in a clinical
      perspective. The main challenges appear to be the following: (1) To better
      understand the etiology of gliomas and to differentiate the respective roles of
      environmental and genetic factors. (2) To improve the diagnostic and follow up
      tools, not only through refined neuroimaging techniques but also by discovering
      serum biomarkers. (3) To build a reliable molecular classification of gliomas
      that may be used for diagnostic and therapeutic purposes. (4) To develop a
      "molecular-based" clinical research. Neuro-Oncology has now reached a new
      therapeutic era and many methodological and medico-economic questions need to be
      solved.

PMID- 18829367
TI  - [Review of the general assembly of the morphologists' Association in Bordeaux on
      5 June 2008.]

PMID- 18829368
TI  - [Francois Chaussier (1746-1828). A vision of the anatomic nomenclature based on
      education].
AB  - Francois Chaussier (1746-1828) developed an original point of view concerning the
      anatomic nomenclature teaching and learning. The myology nomenclature proposed by
      Chaussier was based on a very simple concept: the name of a muscle is composed by
      its two attachment points. He wanted to make science learning easier for the
      students; that we can see in his myology nomenclature, his publications and
      anatomical drawings. His experience is still interesting nowadays.

PMID- 18829369
TI  - Diagnostic evaluation and classification criteria in Sjogren's Syndrome.
AB  - OBJECTIVES: Our objective is to carry out a clinical study of the performance of
      the preliminary European classification criteria for Sjogren Syndrome and that of
      the criteria proposed by the American European Consensus Group. METHODS: Eighty
      eight patients who had undergone a biopsy of the salivary gland on suspicion that
      they were suffering from Sjogren Syndrome were studied by two independent
      rheumatologists. Two pathologists independently revised the biopsies without
      knowing the diagnosis. With all of this information, the clinicians established,
      or did not establish, a diagnosis of primary Sjogren Syndrome or secondary
      Sjogren Syndrome. Finally, it was analysed whether or not the patients met the
      American European Consensus Group classification criteria and the preliminary
      European criteria for primary Sjogren Syndrome and secondary Sjogren Syndrome,
      and their sensitivity and specificity with respect to the clinical diagnosis were
      determined. RESULTS: Clinicians estimated that 35 cases (39.8%) had primary
      Sjogren Syndrome (kappa 0.718) and 17 cases (19.3%) had secondary Sjogren
      Syndrome (kappa 0.761). The specificity and sensitivity of American European
      Consensus Group criteria, with regard to the clinical diagnosis, for primary
      Sjogren Syndrome were 97.2% and 48.6%, respectively. For secondary Sjogren
      Syndrome, the specificity was 97.2% and the sensitivity 64.7%. The preliminary
      European criteria for primary Sjogren Syndrome demonstrated a lesser specificity
      (75%), but a higher sensitivity (65.7%). In secondary Sjogren Syndrome the
      specificity reached 97.2% with sensitivity at 70.6%. CONCLUSIONS: These results
      underline the difficulty in applying the Sjogren Syndrome classification criteria
      from the American European Consensus Group and the preliminary European criteria,
      in the diagnosis of individual patients.

PMID- 18829370
TI  - [How to define the joint movements unambiguously: proposal of standardization for
      the trapezometacarpal joint].
AB  - In order to define the movements of a joint, clinicians usually use anatomic
      terms. These terms are clearly understandable for a simple movement, defined in
      an anatomic plane. However, these terms are ambiguous for complex movements or
      for movements out of an anatomic plane. This, for instance, is the case for the
      internal-external axial rotation of the trapezometacarpal joint. For the study of
      complex movements, engineers preferentially use methods such as Euler angles,
      which correspond to three angles about three axes chosen in a defined order or
      sequence. Thus, the International Society of Biomechanics has proposed a joint
      coordinate system definition where every axis is associated with a functional
      degree of freedom of the joint. The first and third axes are embedded in the
      proximal and distal segments whilst the second axis, called the "floating" axis,
      is always orthogonal to the other two. The present work deals with the
      application of this concept to the trapezometacarpal joint. The two principal
      degrees of freedom, of flexion-extension and of abduction-adduction are defined
      following classical anatomical axes of respectively the trapezium and first
      metacarpal. Conversely, internal-external axial rotation is defined about the
      "floating" axis which does not have anatomical definition but can be
      geometrically deduced from the two others.

PMID- 18829371
TI  - Application of ultrasonics to enhance the efficiency of cleaning Thelephora
      ganbajun.
AB  - The Thelephora ganbajun is a rare edible mushroom which is distributed only in
      Yunnan area of China. It grows generally in the red soil under Burma pine.
      Therefore, there is a lot of dirt on the mushroom. The dirt adheres and embeds on
      the root firmly and deeply, thus to clean them is very difficult. The paper
      reports an efficient method to clean T. ganbajun using ultrasonic cleaner. The
      optimum parameters for ultrasonic clean are: detergent: 0.67%,
      sample:water=1:100, T=21.5-25.0 degrees C, and cleaning time: 20 min. Under the
      optimum condition, the cleaning efficiency can be increased 55.5% than that
      without sonication. Higher cleaning efficiency and more edible parts of the rare
      mushroom was got.

PMID- 18829372
TI  - Model analysis of local oxygen delivery with liposome-encapsulated hemoglobin.
AB  - Liposome-encapsulated hemoglobins (LHs) are comparable to red blood cells (RBCs)
      in terms of oxygen (O(2))-carrying capacity. The smaller particle size of LHs
      than of platelets allows their homogeneous dispersion in circulating plasma. In
      this study, we evaluated the effect of LH transfusion on arterial O(2) delivery
      through vascular trees by simulation. A mathematical model was established on the
      basis of the coronary arterial anatomy, the conservation of flow and RBC flux,
      and Poiseuille's law. The Fahraeus-Lindqvist, Fahraeus, and phase separation
      effects were considered in the model. By assuming steady perfusion, the arterial
      flow and O(2) delivery were calculated for five model trees undergoing the
      isovolumic replacement of RBCs (0.3 mg hemoglobin (Hb)/mL) with LHs (0.2 mg
      Hb/mL) or a plasma volume expander (PVE). The RBC-LH exchange increased both the
      total flow and the total O(2) flux but had almost no effect on the relative
      distribution of O(2) flux. In contrast, the RBC-PVE exchange decreased the total
      O(2) flux and increased the proportion of regions receiving a relatively low O(2)
      supply. Thus, LH transfusion may compensate for an enhanced bias in RBC
      associated O(2) flux under hemodilution and is expected to be beneficial for both
      total and local O(2) delivery.

PMID- 18829373
TI  - Preservation of quadrature Doppler signals from bidirectional slow blood flow
      close to the vessel wall using an adaptive decomposition algorithm.
AB  - A novel approach based on the phasing-filter (PF) technique and the empirical
      mode decomposition (EMD) algorithm is proposed to preserve quadrature Doppler
      signal components from bidirectional slow blood flow close to the vessel wall.
      Bidirectional mixed Doppler ultrasound signals, which were echoed from the
      forward and reverse moving blood and vessel wall, were initially separated to
      avoid the phase distortion of quadrature Doppler signals (which is induced from
      direct decomposition by the nonlinear EMD processing). Separated unidirectional
      mixed Doppler signals were decomposed into intrinsic mode functions (IMFs) using
      the EMD algorithm and the relevant IMFs that contribute to blood flow components
      were identified and summed to give the blood flow signals, whereby only the
      components from the bidirectional slow blood flow close to the vessel wall were
      retained independently. The complex quadrature Doppler blood flow signal was
      reconstructed from a combination of the extracted unidirectional Doppler blood
      flow signals. The proposed approach was applied to simulated and clinical Doppler
      signals. It is concluded from the experimental results that this approach is
      practical for the preservation of quadrature Doppler signal components from the
      bidirectional slow blood flow close to the vessel wall, and may provide more
      diagnostic information for the diagnosis and treatment of vascular diseases.

PMID- 18829374
TI  - Professor Karl-Axel Ekbom and restless legs syndrome.
AB  - The authors provide an historical review of restless legs syndrome, emphasizing
      the contribution of Professor Karl-Axel Ekbom, the Swedish neurologist who made
      the first detailed clinical description of this disease.

PMID- 18829376
TI  - Validity and reliability of ultrasonography for the longus colli in asymptomatic
      subjects.
AB  - The purposes of this study were to evaluate the reliability and validity of
      ultrasound (US) for measuring the cross-sectional area (CSA) of the longus colli
      (LC) as compared with magnetic resonance imaging (MRI), and to determine the
      change in CSA of the LC during contraction. 27 healthy volunteers participated in
      the study. In order to assess the validity of US, the US measurements of the CSA
      of the LC were compared to those determined with MRI. Two testers established the
      measurements to ascertain intra- and interrater reliability. The widely spaced
      limits of agreement (2SD=+/-0.45) reflect the large variability between the
      measurements by US and MRI. The ICC for the intra- and interrater reliability for
      the CSA of the LC was respectively 0.71 (95% CI, 0.57-0.81; SEM, 0.17; SDD, 0.48)
      and 0.68 (95% CI, 0.48-0.81; SEM, 0.18; SDD, 0.50). The CSA of the LC increased
      significantly during contraction of the LC (p=0.006). Results from this study
      show that the validity and reliability of US to evaluate the CSA of the LC is
      questionable, which may be due to both anatomical characteristics and
      methodological limitations.

PMID- 18829375
TI  - Glucosidase-beta variations and Lewy body disorders.
AB  - It has been proposed that there is an increased frequency of glucosidase-beta
      mutations in Lewy body disorders. Our comprehensive DNA sequencing approach found
      a small number of glucosidase-beta mutations in 101 neuropathologically defined
      Lewy body disease cases (3%) compared to 99 healthy post-mortem controls (1%);
      odds ratio 3.0 (95% CI: 0.3-29, p=0.3). All three affected carriers were
      classified as diffuse Lewy body disease (n=3/50; 6%). Our study suggests
      glucosidase-beta variants have a limited role in susceptibility to Lewy body
      disease in North America.

PMID- 18829377
TI  - Mycorrhizal respiration: implications for global scaling relationships.
AB  - Most plant species form mycorrhizas, yet these are neglected by plant
      physiologists. One consequence of this neglect is reduced ability to predict
      plant respiration, because respiration rate (R) in mycorrhizal roots might be
      higher than in non-mycorrhizal roots owing to increased substrate availability
      associated with enhanced nutrient uptake, coupled with increased respiratory
      product demand. Other predictions include that mycorrhizal colonization will
      affect scaling of R with tissue nitrogen concentrations; that mycorrhizal and non
      mycorrhizal root R differ in their response to nutrient supply; and that the
      impact of colonization on R is related to fungal biomass. Failure to examine
      properly the role of colonization in determining root R means that current
      interpretations of root and soil respiration data might be flawed.

PMID- 18829378
TI  - Theoretical study of the vibrational spectra of the hydrogen-bonded systems
      between pyridine-3-carboxamide (nicotinamide) and DMSO.
AB  - The vibrational characteristics (vibrational frequencies and infrared
      intensities) for the hydrogen-bonded systems of nicotinamide (NA(Z) and NA(E))
      with dimethyl sulfoxide (DMSO) have been predicted using ab initio SCF/6-31G(d,p)
      and DFT (BLYP/6-311++G(d,p)) calculations. The changes in the vibrational
      characteristics from free monomers to a complex have been calculated. The ab
      initio and BLYP calculations show that the complexation between nicotinamide
      (NA(Z) and NA(E)) and DMSO leads to large red shifts of the stretching vibrations
      for the hydrogen-bonded N-H bonds of nicotinamide and very strong increase in
      their IR intensity. The results from the BLYP/6-311++G(d,p) calculations show
      that the predicted red shifts of the nu(s)(NH) and nu(as)(NH) vibrations for the
      complex NA(E)-DMSO (1:2) (Deltanu(as)(NH)=-186 cm(-1) and Deltanu(s)(NH)=-198 cm(
      1)) are in better agreement with the experimentally measured. The magnitudes of
      the wavenumber shifts are indicative of strong NH...O hydrogen-bonded
      interactions in both complexes. The calculations predict an increase of the IR
      intensity of nu(s)(NH) and nu(as)(NH) vibrations in the complexes up to 14 times.
      Having in mind that in more cases the predicted changes in the vibrational
      characteristics for the complexes studied are very near, it could be concluded
      that both conformers of nicotinamide, Z-conformer and E-conformer, are present in
      the solution forming the hydrogen-bonded complexes with DMSO.

PMID- 18829379
TI  - Human herpesvirus type 6 reactivation after haematopoietic stem cell
      transplantation.
AB  - Human herpesvirus type 6 (HHV6) is known to reactivate after hematopoetic stem
      cell transplantation (HSCT) and has been suggested to be associated with
      increased mortality and severe clinical manifestations, including graft versus
      host disease (GvHD). The exact etiological role of HHV6 reactivation in increased
      morbidity and mortality after HSCT remains unclear. This review will focus on the
      current available evidence of HHV6 reactivation after HSCT and its immuno
      modulatory capacities, with particular emphasis on the severe complication GvHD.
      At present, no effective specific antiviral treatment for HHV6 reactivation has
      been identified. The currently available antiviral agents are outlined, as well
      as possible future strategies for the treatment of HHV6 reactivation. Non-toxic,
      specific treatment or prevention of HHV6 reactivation might improve the safety
      and efficacy of the HSCT procedure.

PMID- 18829380
TI  - Mixed respiratory virus infections.
AB  - Mixed respiratory viral infections are double negative common and evidence that
      they are associated with severe disease is supported by some groups. This
      controversial observation can be explained by the lack of sensitivity of the
      assessed methods used for viral identification and by the small number of
      patients included in the randomized cohorts studied. Most studies showed that
      respiratory syncytial virus (RSV) is identified in about 70% of hospitalized
      infants with bronchiolitis during seasonal winter epidemics, followed by human
      metapneumovirus (hMPV, about 3-19%) or rhinoviruses (about 20%). Other
      respiratory viruses have also been reported, indicating significant causes of
      bronchiolitis and hospitalization during seasonal epidemics. The presence of more
      than one pathogen, and moreover, the association of RSV with rhinoviruses and
      also RSV with hMPV, may influence the natural course of bronchiolitis. A better
      understanding of these various interactions would help future decision-making,
      such as the extent to which searches for co-pathogens should be conducted in
      severe bronchiolitis patients already infected by RSV.

PMID- 18829381
TI  - Immune-mediated neuropathies in myeloma patients treated with bortezomib.
AB  - OBJECTIVE: Bortezomib is a new chemotherapeutic drug available for the treatment
      of lymphoid disorders, including multiple myeloma. Although its primary mechanism
      of action is proteasome inhibition, other mechanisms can contribute to the
      therapeutic effects, including modulation of inflammatory cytokines and immune
      response. One of the main toxic effects of bortezomib is peripheral neuropathy,
      usually occurring in the form of a painful, sensory axonal neuropathy. The
      mechanisms of peripheral damage, however, are still unclear. We here report a
      series of patients treated with bortezomib, who developed a peripheral damage
      possibly related to immuno-mediated, rather than toxic, mechanisms. METHODS: Five
      patients who developed a peripheral neuropathy with severe motor involvement
      under bortezomib treatment underwent CSF, electrophysiological, and spinal cord
      MRI examinations. RESULTS: Peripheral damage was characterized by: demyelinating
      or mixed axonal-demyelinating neuropathy, with prominent motor involvement;
      albumin-cytological dissociation; lumbar root enhancement on MRI in 2/5 patients;
      favourable outcome in 4/5 patients after immune treatments, either steroids (2
      patients) or IVIg (2 patients). CONCLUSIONS: In some instances, the peripheral
      damage associated with bortezomib may recognize immuno-mediated mechanisms.
      SIGNIFICANCE: This form of bortezomib-associated neuropathy needs to be
      recognized as treatable condition, as it may respond to immune therapies.
      Unexplained worsening of neurological dysfunction despite bortezomib
      discontinuation, with prominent motor involvement and CSF signs of inflammation,
      may be the clues to this complication.

PMID- 18829382
TI  - Nonlinear interactions of high-frequency oscillations in the human somatosensory
      system.
AB  - OBJECTIVE: The source of somatosensory evoked high-frequency activity at about
      600 Hz is still not completely clear. Hence, we aimed to study the influence of
      double stimulation on the human somatosensory system by analyzing both the low
      frequency activity and the high-frequency oscillations (HFOs) at about 600 Hz.
      METHODS: We used median nerve stimulation at seven interstimuli intervals (ISIs)
      with a high time resolution between 2.4 and 4.8 ms to investigate the N15, N20
      and superimposed HFOs. Simultaneously, the electroencephalogram and the
      magnetoencephalogram of 12 healthy participants were recorded. Subsequently, the
      source analysis of precortical and cortical dipoles was performed. RESULTS: The
      difference computations of precortical dipole activation curves showed in both
      the low- and high-frequency range a correlation between the ISI and the latency
      of the second stimulus response. The cortical low-frequency response showed a
      similar behavior. Contrarily, in the second response of cortical HFOs this
      latency shift could not be confirmed. We found amplitude fluctuations that were
      dependent on the ISI in the low-frequency activity and the HFOs. These nonlinear
      interactions occurred at ISIs, which differ by one full HFO period (1.6 ms).
      CONCLUSIONS: Low-frequency activity and HFOs originate from different generators.
      Precortical and cortical HFOs are independently generated. The amplitude
      fluctuations dependent on ISI indicate nonlinear interference between successive
      stimuli. SIGNIFICANCE: Information processing in human somatosensory system
      includes nonlinearity.

PMID- 18829383
TI  - Neonatal seizure detection.

PMID- 18829384
TI  - In vivo functional evaluation of central cholinergic circuits in vascular
      dementia.
AB  - OBJECTIVE: Central cholinergic circuits of human brain can be tested non
      invasively by coupling peripheral nerve stimulation with transcranial magnetic
      stimulation of motor cortex. This test, named short latency afferent inhibition
      (SAI) has been shown in healthy subjects to be sensitive to the blockage of
      muscarinic acetylcholine receptors and it is impaired in Alzheimer disease (AD)
      patients, a cholinergic form of dementia, while it is normal in non-cholinergic
      forms of dementia such as fronto-temporal dementia. The objective of present
      study was to evaluate central cholinergic circuits in patients with Vascular
      Dementia (VaD). METHODS: We evaluated SAI in a group of patients with VaD and
      compared the data with those from a group of AD patients and a control group of
      age-matched healthy individuals. RESULTS: Mean SAI was normal in VaD patients
      while it was significantly reduced in AD patients. The analysis of individual
      data showed abnormal SAI in 75% of AD and in only 25% of VaD. CONCLUSIONS: SAI is
      normal in most of VaD patients in contrast with AD patients. This test might be
      used for the functional evaluation of central cholinergic circuits in VaD
      patients. SIGNIFICANCE: SAI testing may represent a useful additional tool for
      the evaluation of patients with VaD however, further studies are required in
      order to evaluate whether this method can be used for the differential diagnosis
      between pure VaD and different forms of dementia.

PMID- 18829385
TI  - Comparison of acute, chronic and post-treatment effects of carbamazepine and
      vinpocetine on hearing loss and seizures induced by 4-aminopyridine.
AB  - OBJECTIVE: To compare the acute, chronic and post-treatment effects of the
      classic antiepileptic drug carbamazepine (CBZ) and the potential antiepileptic
      vinpocetine (VPC), successfully used in the treatment of brain vascular origin
      disorders, on 4-aminopyridine (4-AP)-induced increase in auditory threshold,
      brain-auditory-evoked-potentials (BAEPs) later waves alterations and epileptiform
      activity. METHODS: BAEP and EEG recordings before and following 4-AP (3mg/kg,
      i.p.) were obtained in guinea pigs. One week after, the animals received a daily
      injection (i.p.) of vehicle, 3mg/kg VPC or 17 mg/kg CBZ for 13 days. The acute
      and chronic effects before and following 4-AP were tested at the 1st and last
      days, respectively, and the post-treatment effect 1 month after the end of
      treatment. RESULTS: CBZ and 4-AP increased BAEPs threshold and BAEPs P4 wave
      latency. Chronic CBZ inhibited 4-AP-induced increase in P3 amplitude. In the VPC
      treated group, all the 4-AP-induced BAEPs changes were prevented. Seizures were
      prevented in 50% and 75% of the animals by chronic CBZ and VPC, respectively.
      After acute VPC and after the end of VPC-treatment 4-AP failed to induce seizures
      in 50% of the animals. CONCLUSION: VPC inhibits 4-AP-induced seizures and hearing
      loss, even after post-treatment, at a concentration about 10 times lower than
      CBZ. SIGNIFICANCE: The complications in hearing that can accompany epilepsy can
      be prevented by VPC, indicating its advantage as an alternative antiepileptic.

PMID- 18829386
TI  - Initial characterization of Chlamydophila (Chlamydia) pneumoniae cultured from
      the late-onset Alzheimer brain.
AB  - Previous studies from this laboratory provided evidence that the intracellular
      bacterial pathogen Chlamydophila (Chlamydia) pneumoniae is present in the late
      onset Alzheimer's disease (AD) brain. Here we report culture of the organism from
      two AD brain samples, each of which originated from a different geographic region
      of North America. Culturable organisms were detectable after one and two passages
      in HEp-2 cells for the two samples. Both isolates, designated Tor-1 and Phi-1,
      were demonstrated to be authentic C. pneumoniae using PCR assays targeting the C.
      pneumoniae-specific genes Cpn0695, Cpn1046, and tyrP. Assessment of inclusion
      morphology and quantitation of infectious yields in epithelial (HEp-2),
      astrocytic (U-87 MG), and microglial (CHME-5) cell lines demonstrated an active,
      rather than a persistent, growth phenotype for both isolates in all host cell
      types. Sequencing of the omp1 gene from each isolate, and directly from DNA
      prepared from several additional AD brain tissue samples PCR-positive for C.
      pneumoniae, revealed genetically diverse chlamydial populations. Both brain
      isolates carry several copies of the tyrP gene, a triple copy in Tor-1, and
      predominantly a triple copy in Phi-1 with a minor population component having a
      double copy. This observation indicated that the brain isolates are more closely
      related to respiratory than to vascular/atheroma strains of C. pneumoniae.

PMID- 18829387
TI  - The metabolic pH response in Lactococcus lactis: an integrative experimental and
      modelling approach.
AB  - Lactococcus lactis is characterised by its ability to convert sugar almost
      exclusively into lactic acid. This organic acid lowers extracellular pH, thus
      inhibiting growth of competing bacteria. Although L. lactis is able to survive at
      low pH, glycolysis is strongly affected at pH values below 5, showing reduced
      rate of glucose consumption. Therefore, in order to deepen our knowledge on
      central metabolism of L. lactis in natural or industrial environments, an
      existing full scale kinetic model of glucose metabolism was extended to simulate
      the impact of lowering extracellular pH in non-growing cells of L. lactis MG1363.
      Validation of the model was performed using (13)C NMR, (31)P NMR, and
      nicotinamide adenine dinucleotide hydride auto-fluorescence data of living cells
      metabolizing glucose at different pH values. The changes in the rate of
      glycolysis as well as in the dynamics of intracellular metabolites (NADH,
      nucleotide triphosphates and fructose-1,6-bisphosphate) observed during glucose
      pulse experiments were reproduced by model simulations. The model allowed
      investigation of key enzymes at sub-optimum extracellular pH, simulating their
      response to changing conditions in the complex network, as opposed to in vitro
      enzyme studies. The model predicts that a major cause of the decrease in the
      glycolytic rate, upon lowering the extracellular pH, is the lower pool of
      phosphoenolpyruvate available to fuel glucose uptake via the phosphoenolpyruvate
      dependent transport system.

PMID- 18829388
TI  - Type 1 diabetes patients have significantly lower frequency of plasmacytoid
      dendritic cells in the peripheral blood.
AB  - Dendritic cells uniquely orchestrate the delicate balance between T cell immunity
      and regulation and an imbalance favoring immunogenic rather than tolerogenic DC
      is believed to contribute to the development of autoimmune diseases such as type
      1 diabetes (T1D). In this study, we determined the frequencies of three blood DC
      subsets (pDC, mDC1 and mDC2) in 72 T1D patients and 75 normal controls using the
      Miltenyi blood DC enumeration kit. The frequency of blood pDC was found to be
      negatively correlated with subject age in both normal controls and T1D patients
      (p=0.0007), while the frequency of mDC1 and mDC2 do not change significantly with
      subject age. More importantly, the mean frequency of pDC in blood was, after
      adjusting for age, significantly lower in T1D (mean=0.127%) than controls
      (mean=0.188%) (p<6.0 x 10(-5)), whereas no difference was observed for mDC1 and
      mDC2 between T1D and controls. Furthermore, T1D patients have a lower proportion
      of pDC and higher proportion of mDC1 among the total blood DC population than
      normal controls. These results indicate that the frequency of blood pDC and the
      pDC/mDC1 ratio are negatively associated with T1D.

PMID- 18829389
TI  - A gap in our understanding: chronic constipation and its comorbid conditions.
AB  - Constipation is one of the most common digestive disorders in the United States;
      however, the association of this condition with related comorbidities, both
      gastrointestinal and extraintestinal, is poorly documented. Here, we have
      reviewed the association of constipation with specific comorbidities. The data
      suggest that there are considerable clinical consequences associated with
      constipation. Ultimately, realization of the disease risks associated with
      chronic constipation may provide the impetus needed to direct new research, and
      shift attention on the part of patients and practitioners to methods for
      preventing significant and potentially costly comorbid medical problems.

PMID- 18829390
TI  - Persistent nausea and abdominal pain in a patient with delayed gastric emptying.

PMID- 18829391
TI  - Placebo in nonalcoholic steatohepatitis: insight into natural history and
      implications for future clinical trials.
AB  - BACKGROUND & AIMS: Changes in biochemical and histologic parameters related to
      nonalcoholic steatohepatitis (NASH) in placebo-treated patients may provide an
      insight into the natural history and help in defining treatment end points in
      NASH. The aim of our study was to assess the biochemical and histologic changes
      seen in the placebo arm of the randomized, placebo-controlled trials in adult
      patients with NASH. METHODS: Medline was searched (through May 2008) for studies
      published in the English language. Randomized, placebo-controlled trials of at
      least 6 months' duration in patients with NASH that provided biochemical and/or
      histologic data of the placebo arm were included. One investigator performed the
      literature search and data extraction. Two investigators independently confirmed
      that the studies met prespecified criteria. Pooled estimates of biochemical and
      histologic parameters associated with NASH were calculated. RESULTS: Five
      randomized controlled trials met the predefined criteria and included 162 placebo
      treated and 189 active-treatment patients. The mean serum alanine and aspartate
      aminotransferase levels decreased on placebo. A 1-point improvement in steatosis,
      ballooning degeneration, lobular inflammation, NASH fibrosis, and combined
      inflammation scores was seen in 31%, 15%, 33%, 22%, and 32% of patients,
      respectively. A 2-point improvement in NASH histologic scores is rarely seen.
      CONCLUSIONS: Serum alanine aminotransferase levels may decrease on placebo and is
      not a reliable measure of treatment response. Although a 1-point improvement is
      seen in a third of patients, a 2-point improvement in histologic parameters is
      rarely seen in the placebo arm and may be more reliable in assessing treatment
      response. These data may have important implications in designing future clinical
      trials in NASH.

PMID- 18829392
TI  - Treatment of active Crohn's disease with MLN0002, a humanized antibody to the
      alpha4beta7 integrin.
AB  - BACKGROUND & AIMS: Selective blockade of lymphocyte-vascular endothelium
      interactions in the gastrointestinal tract is a promising therapeutic strategy
      for inflammatory bowel disease. This randomized, double-blind, controlled trial
      assessed the efficacy and safety of MLN0002, a monoclonal antibody targeting the
      alpha4beta7 integrin, in patients with active Crohn's disease. METHODS: Patients
      were randomized to receive MLN0002 2.0 mg/kg (n = 65), MLN0002 0.5 mg/kg (n =
      62), or placebo (n = 58) by intravenous infusion on days 1 and 29. The primary
      efficacy end point was clinical response (>or=70-point decrement in the Crohn's
      Disease Activity Index [CDAI] score) on day 57. Secondary end points were the
      proportions of patients with clinical remission (CDAI score <or=150) and with an
      enhanced clinical response (>or=100-point decrement in CDAI). Human anti-human
      antibody levels were measured. RESULTS: Clinical response rates at day 57 were
      53%, 49%, and 41% in the MLN0002 2.0 mg/kg, MLN0002 0.5 mg/kg, and placebo
      groups. Clinical remission rates at day 57 were 37%, 30%, and 21%, respectively
      (P = .04 for the 2.0 mg/kg vs placebo comparison). At day 57, 12% and 34% of
      patients in the 2.0- and 0.5-mg/kg groups had clinically significant human anti
      human antibody levels (titers > 1:125). There was one infusion-related
      hypersensitivity reaction. The most common serious adverse event was worsening of
      Crohn's disease. CONCLUSIONS: This phase 2 study was suggestive of a dose
      dependent beneficial effect of MLN0002 therapy on clinical remission. MLN0002 was
      well tolerated in patients with active Crohn's disease.

PMID- 18829394
TI  - Where the twains should meet.

PMID- 18829393
TI  - The effect of hospital and surgeon volume on outcomes for rectal cancer surgery.
AB  - Despite many studies of rectal cancer outcomes, no clear relationship between
      hospital or surgeon volume and patient outcomes has emerged for rectal cancer. We
      aimed to characterize the effect of hospital and surgical volume on surgery type
      and surgical outcomes in rectal cancer through a systematic review of the
      literature. We conducted a systematic review of studies evaluating the
      association between hospital or surgeon volume and rectal cancer outcomes. We
      searched PubMed for relevant articles and reviewed 23 articles. We describe each
      study and report outcomes in terms of the effect of hospital or surgeon volume on
      the type of surgery performed, surgical complications, postoperative mortality,
      survival, and recurrence. Hospitals and surgeons with higher caseloads appear to
      perform more sphincter-preserving surgeries and have lower postoperative
      mortality rates. Hospital and surgeon volume appear to have no effect or a small
      beneficial effect on the rate of leaks, complication rates, local recurrence,
      overall survival, and cancer-specific survival. For rectal cancer, the effects of
      hospital volume may be stronger for more short-term outcomes. Beyond the
      immediate recovery period, the effect of hospital and surgeon volume may be
      minimal. As more technically challenging surgeries, such as total mesorectal
      resection, become more widespread it will be important to evaluate the impact of
      hospital and surgeon volume on outcomes.

PMID- 18829395
TI  - The yield of surveillance colonoscopy by adenoma history and time to examination.
AB  - BACKGROUND & AIMS: Surveillance colonoscopy is recommended for subjects with a
      history of adenomas but there is limited information on the yield of
      surveillance. METHODS: A sample of subjects in the Prostate, Lung, Colorectal,
      and Ovarian (PLCO) Cancer Screening Trial with abnormal flexible sigmoidoscopy
      and follow-up colonoscopy were queried about subsequent surveillance colonoscopy
      over a 10-year period. Medical records were obtained to verify procedure dates
      and histologic findings. Subjects with advanced adenomas, nonadvanced adenoma,
      nonadenomatous polyps, and no polyps at baseline were included. RESULTS: At the
      first surveillance, 10.5% had advanced adenoma and 37% had any adenoma in the
      advanced adenoma group (n = 1057), compared with rates of 6.8% and 32%
      (nonadvanced adenoma: n = 765), 4.9% and 22% (nonadenomatous polyps: n = 658),
      and 3.1% and 16% (no polyps: n = 127) (P < .0001, linear trend test). Mean (SD)
      time intervals (years) from baseline colonoscopy to first surveillance were 3.4
      (2.0) for advanced adenoma, 4.3 (2.0) for nonadvanced adenoma, 4.5 (2.0) for
      nonadenomatous polyps, and 4.7 (2.0) for no polyps. There were no increasing (or
      decreasing) trends in the observed rate of advanced adenoma or any adenoma with
      time to the initial surveillance examination in any baseline group. Among
      subjects with a second surveillance examination, adenoma findings at both
      baseline and first surveillance influenced the rates of advanced adenoma and any
      adenoma at second surveillance. CONCLUSIONS: Subjects with baseline advanced
      adenomas are more likely to have recurrent advanced adenomas at initial
      surveillance. The lack of association between recurrence rates and time to
      surveillance suggests limitations in our understanding of the biology of adenoma
      development.

PMID- 18829397
TI  - Adsorption and release behavior of bare and DNA-wrapped-carbon nanotubes on self
      assembled monolayer surface.
AB  - The adsorption and release behavior of single-stranded DNA-wrapped single-walled
      carbon nanotubes (ssDNA-w-SWCNTs) on alkylthiol self-assembled monolayer (SAM)
      surface was systematically characterized by cyclic voltammetry (CV) and
      electrochemical impedance spectroscopy (EIS). Fast electron transfer between bare
      Au electrode and redox species blocked by the alkylthiol SAM can be restored by
      SWCNTs or ssDNA-w-SWCNTs. The release of ssDNA-w-SWCNTs is carried out by
      positive or negative desorption potential. SWCNTs/SAM or ssDNA-w-SWCNTs/SAM is
      completely removed from Au surface at +0.90 V or -1.40 V (vs. 3.0 M KCl|Ag|AgCl).
      The controlled release of SWCNTs/SAM and ssDNA-w-SWCNTs/SAM holds great promise
      for gene delivering.

PMID- 18829396
TI  - Targeting of albumin-embedded paclitaxel nanoparticles to tumors.
AB  - We have used tumor-homing peptides to target abraxane, a clinically approved
      paclitaxel-albumin nanoparticle, to tumors in mice. The targeting was
      accomplished with two peptides, CREKA and LyP-1 (CGNKRTRGC). Fluorescein (FAM)
      labeled CREKA-abraxane, when injected intravenously into mice bearing MDA-MB-435
      human cancer xenografts, accumulated in tumor blood vessels, forming aggregates
      that contained red blood cells and fibrin. FAM-LyP-1-abraxane co-localized with
      extravascular islands expressing its receptor, p32. Self-assembled mixed micelles
      carrying the homing peptide and the label on different subunits accumulated in
      the same areas of tumors as LyP-1-abraxane, showing that Lyp-1 can deliver intact
      nanoparticles into extravascular sites. Untargeted, FAM-abraxane was detected in
      the form of a faint meshwork in tumor interstitium. LyP-1-abraxane produced a
      statistically highly significant inhibition of tumor growth compared with
      untargeted abraxane. These results show that nanoparticles can be effectively
      targeted into extravascular tumor tissue and that targeting can enhance the
      activity of a therapeutic nanoparticle.

PMID- 18829398
TI  - Regimens for eradicating early Pseudomonas aeruginosa infection in children do
      not promote antibiotic resistance in this organism.
AB  - BACKGROUND: This study was designed to address the concern that intensive
      regimens to eradicate early Pseudomonas aeruginosa infection in patients with
      cystic fibrosis may lead to the emergence of antibiotic-resistant isolates.
      METHODS: Data was analysed retrospectively over a 10 year period at the Leeds
      Regional Paediatric Cystic Fibrosis Centre. All patients with first-ever
      isolation of P. aeruginosa who successfully completed an eradication regimen were
      included. Antibiotic sensitivities of P. aeruginosa were compared between initial
      and subsequent re-isolations in patients where eradication was successful and in
      those where treatment had failed. RESULTS: Forty one patients with first
      acquisitions for P. aeruginosa and who completed eradication treatment were
      identified. Eradication treatments consisted of oral, intravenous, nebulised
      antibiotics or a combination of these. The antibiotic sensitivity of P.
      aeruginosa in first growths was high and remained so on subsequent re-isolations.
      A repeated measures logistic model found no significant difference with time of
      isolation. There was no statistically significant difference in antibiotic
      sensitivity between P. aeruginosa isolated after successful and failed
      eradication. CONCLUSIONS: Repeated intensive regimens for P. aeruginosa
      eradication did not result in a significant increase in overall antibiotic
      resistance between initial and subsequent growths of this organism over the
      period of this study.

PMID- 18829399
TI  - An automated SPE/LC/MS/MS method for the analysis of cocaine and metabolites in
      whole blood.
AB  - As laboratories are called upon to develop novel, fast, and sensitive methods,
      here we present a completely automated method for the analysis of cocaine and its
      metabolites (benzoylecgonine, ecgonine methyl ester, ecgonine and cocaethylene)
      from whole blood. This method utilizes an online solid-phase extraction (SPE)
      with high performance liquid chromatographic separation and tandem mass
      spectrometric detection. Pretreatment of samples involve only protein
      precipitation and ultracentrifugation. An efficient online solid-phase extraction
      (SPE) procedure was developed using Hysphere MM anion sorbent. A gradient
      chromatography method with a Gemini C6-Phenyl (50mmx3.00mm i.d., 5microm) column
      was used for the complete separation of all components. Analysis was by positive
      ion mode electrospray ionization tandem mass spectrometry, using multiple
      reaction monitoring (MRM) to enhance the selectivity and sensitivity of the
      method. For the analysis, two MRM transitions are monitored for each analyte and
      one transition is monitored for each internal standard. With a 30-microL sample
      injection, linearity was analyte dependent but generally fell between 8 and
      500ng/mL. The limits of detection (LODs) for the method ranged from 3 to 16ng/mL
      and the limits of quantitation (LOQs) ranged from 8 to 47ng/mL. The bias and
      precision were determined using a simple analysis of variance (ANOVA: single
      factor). The results demonstrate bias as <7%, and %precision as <9% for all
      components at each QC level.

PMID- 18829400
TI  - Liquid chromatographic-electrospray ionization mass spectrometric assay for
      simultaneous determination of 3,4-methylenedioxymethamphetamine and its
      metabolites 3,4-methylenedioxyamphetamine, 3,4-dihydroxymethamphetamine, and 4
      hydroxy-3-methoxymethamphetamine in rat brain.
AB  - 3,4-Methylenedioxymethamphetamine (MDMA) is a psychoactive drug with abuse
      liability and neurotoxic potential. Mechanisms by which MDMA produces behavioral
      and neurotoxic effects have yet to be elucidated. By measuring concentrations of
      MDMA and its metabolites in relevant brain sites, it may be possible to gain
      insight into mechanisms underlying MDMA actions. For this purpose, an LC-MS assay
      with electrospray ionization was developed after homogenization of rat brain and
      enzymatic conjugate cleavage. The method was successfully validated with respect
      to selectivity, linearity, accuracy, precision, recovery, and matrix effect and
      its use should help to delineate the neurotoxic mechanism of action of MDMA.

PMID- 18829401
TI  - Gastric xanthomatosis associated with gastric intestinal metaplasia in a
      dyspeptic patient.

PMID- 18829402
TI  - Structure, chemical composition and mechanical properties of human and rat
      cementum and its interface with root dentin.
AB  - This work seeks to establish comparisons of the physical properties of rat and
      human cementum, root dentin and their interface, including the cementum-dentin
      junction (CDJ), as a basis for future studies of the entire periodontal complex
      using rats as animal models. In this study the structure, site-specific chemical
      composition and mechanical properties of cementum and its interface with root
      dentin taken from 9- to 12-month-old rats were compared to the physiologically
      equivalent 40- to 55-year-old human age group using qualitative and quantitative
      characterization techniques, including histology, atomic force microscopy (AFM),
      micro-X-ray computed tomography, Raman microspectroscopy and AFM-based
      nanoindentation. Based on results from this study, cementum taken from the apical
      third of the respective species can be represented as a woven fabric with
      radially and circumferentially oriented collagen fibers. In both species the
      attachment of cementum to root dentin is defined by a stiffness-graded interface
      (CDJ/cementum-dentin interface). However, it was concluded that cementum and the
      cementum-dentin interface from a 9- to 12-month-old rat could be more
      mineralized, resulting in noticeably decreased collagen fiber hydration and
      significantly higher modulus values under wet conditions for cementum and CDJ
      (E(rat-cementum)=12.7+/-2.6 GPa; E(rat-CDJ)=11.6+/-3.2 GPa) compared to a 40- to
      55-year-old human (E(human-cementum)=3.73+/-1.8 GPa; E(human-CDJ)=1.5+/-0.7 GPa).
      The resulting data illustrated that the extensions of observations made from
      animal models to humans should be justified with substantial and equivalent
      comparison of data across age ranges (life spans) of mammalian species.

PMID- 18829403
TI  - Electrical characterization of hydroxyapatite-based bioceramics.
AB  - This paper studies the AC conductivity and permittivity of hydroxyapatite (HA)
      based ceramics from 0.1 Hz-1 MHz at temperatures from room temperature to 1000
      degrees C. HA-based ceramics were prepared either as dense ceramics or in porous
      form with interconnected porosity and were sintered in either air or water
      vapour. Samples were thermally cycled to examine the influence of water
      desorption on AC conductivity and permittivity. Surface-bound water was thought
      to contribute to conductivity for both dense and porous materials at temperatures
      below 200 degrees C. At temperatures below 700 degrees C the permittivity and AC
      conductivity of HA was also influenced by the degree of dehydration and thermal
      history. At higher temperatures (700-1000 degrees C), bulk ionic conduction was
      dominant and activation energies were of the order of approximately 2 eV,
      indicating that hydroxyl ions are responsible for conductivity.

PMID- 18829404
TI  - Evaluation of adhesive properties of three resilient denture liners by the
      modified peel test method.
AB  - The characteristics of adhesive properties between a denture base and resilient
      denture liner were investigated by a modified peel test with an L-shaped metal
      attachment. Three commercially resilient denture lining materials, namely GC
      Reline Soft (S), GC Reline Extra Soft (ES), and GC Reline Ultra Soft (US), were
      evaluated. Acrylic resin (GC Acron) was used as denture base material. Peel
      specimens consisting of the denture base acrylic resin and resilient denture
      liner were tested after storage for 1 and 30 days in distilled water at 37
      degrees C. The modified peel test method gave load-displacement curves and work
      of adhesion (W(A)) values of the denture base material and resilient denture
      liner. The W(A) of specimens after 1 day of storage ranged from 1.71 to 2.55 N
      mm(-1) and increased in the order from US to S to ES. On the other hand, the W(A)
      of specimens after 30 day of storage ranged from 1.44 to 2.47 N mm(-1) and
      increased in the order from US to ES to S. US had significantly lower W(A) after
      1 and 30 days of storage than did S and ES (P<0.05). Comparison of the W(A)
      between 1 and 30 days, reveals large differences for ES and US, but not for S.
      This could be explained by the difference in failure modes. Within the
      limitations of this investigation, it was concluded the modified peel test is
      effective for evaluating the adhesion between denture base material and a
      resilient denture liner.

PMID- 18829405
TI  - Automated respiratory support in newborn infants.
AB  - A considerable proportion of premature infants requires mechanical ventilatory
      support and supplemental oxygen. Due to their immaturity, exposure to these forms
      of respiratory support contributes to the development of lung injury, oxidative
      stress and abnormal retinal development. These conditions are associated with
      poor long-term respiratory and neurological outcome. Mechanically ventilated
      preterm infants present with frequent fluctuations in ventilation and gas
      exchange. Currently available ventilatory modes and manual adjustment to the
      ventilator or supplemental oxygen cannot effectively adapt to these recurrent
      fluctuations. Moreover, the respiratory support often exceeds the infant's real
      needs. Techniques that adapt the mechanical ventilatory support and supplemental
      oxygen to the changing needs of preterm infants are being developed in order to
      improve stability of gas exchange, to minimise respiratory support and to reduce
      personnel workload. This article describes the preliminary evidence on the
      application of these new techniques in preterm infants and animal models.

PMID- 18829406
TI  - Lateral pillar suspension in vertical-scar mammaplasty.

PMID- 18829407
TI  - Effective use of Burow's triangle in a nasolabial flap--a technique.

PMID- 18829408
TI  - The anatomy and application of the postauricular fascia flap in auricular
      reconstruction for congenital microtia.
AB  - BACKGROUND: The various layers of the scalp are widely used in reconstructive
      procedures. The technique used for soft tissue coverage seems to influence the
      framework extrusion rate in auricular reconstruction. We have investigated the
      role of the postauricular fascial flap in providing ample, thin neurovascular
      cover to facilitate ear reconstruction in congenital microtia. METHODS: Following
      postauricular cutaneous tissue expansion, the postauricular neurovascular fascia
      flap was raised to partially cover the projected three-dimensional autogenous
      cartilage framework. A suction drain was placed in the pocket to allow the skin
      to coapt to the framework and a split-thickness skin graft was applied to
      complete coverage. RESULTS: At final assessment, the aesthetic results were
      analysed subjectively. Four hundred and thirty-eight ears underwent total ear
      reconstruction in 428 patients using the postauricular fascial flap technique.
      None of the reconstructions failed, and all patients were satisfied with the
      results. CONCLUSIONS: The use of a postauricular fascial flap and skin graft
      enhances safety and provides better vascularisation of the underlying cartilage.

PMID- 18829409
TI  - Commentary on "Gastro-omental free flap in the reconstruction of the unfavorable
      hypopharyngeal defects: a functional assessment".

PMID- 18829410
TI  - Trends in the management of risk of diabetes complications in different ethnic
      groups in New Zealand primary care.
AB  - AIMS: To assess changes over two years in the health status and management of a
      cohort of people with Type 2 diabetes from different ethnic groups within a
      primary care diabetes annual review programme in New Zealand. METHODS: The study
      evaluated changes in clinical measures and proportions achieving guideline
      targets for 7782 people who had data recorded at baseline in 2002-2003 and at
      follow-up two years later within the diabetes programme. RESULTS: A large
      proportion of Maori (47%) and Pacific (69%) patients had poor glycaemic control
      at baseline and only small improvements were made over the two years. Significant
      improvements were made in all the ethnic groups in blood pressure and lipid
      management at two-year follow-up. By the two-year follow-up, over 75% of Maori
      and Pacific patients received appropriate treatment with anti-hypertensive and
      lipid lowering medication and many of the ethnic disparities in risk factors for
      complications were reduced. CONCLUSIONS: Participation in the annual review
      programme may have contributed to improvements in clinical management and reduced
      disparities in a cohort with Type 2 diabetes. However, the removal of
      restrictions on statin use in 2002, and introduction of diabetes management
      guidelines in 2003 may also have improved management standards.

PMID- 18829411
TI  - [Hormonal status and overexpression of HER2 in breast cancer, Cancerology
      department of Treichville UHC. Preliminary results].
AB  - AIMS:  MAIN OBJECTIVE: determine the profile of the hormonal receptors and HER2
      in order to optimize the patient's treatment by hormonotherapy and to propose
      targeted therapeutic to the few patients can procure themselves, when the
      indication is put. SECONDARY OBJECTIVES: show the feasibility of these exams in
      sub-Saharan Africa and also the necessity to improve the technical tray
      permitting to do these exams in routine thus. PATIENTS AND METHODS: Preliminary
      results of a prospective, descriptive study, on 10 months, achieved to the
      Cancerology service of Treichville CHU in Abidjan (Ivory Coast). Our results were
      about 22 patients. RESULTS: The middle age of our patients was of 42.7 years. The
      stages to the diagnosis were advanced (86%) with nodes metastasis (77%), 8
      patients out of 20 were RH+ of which only one postmenopausal patient, 8 patients
      out of 20 were HER2+ of which 2 to 2++ and 6 to 3+++. The FISH test has been
      achieved for the 2 positive patients to 2 ++ by IHC and came back positive. One
      of patients HER2+ could have adjuvant Herceptin. CONCLUSION: Breast cancer is bad
      prognosis affection in our developing countries because of the patient's young
      age, of the advanced stages to the diagnosis. The knowledge of the status of the
      hormonal receptors and the HER2 over expression is necessary, as well the
      importance to pursue this survey and to set up an immunohistochemy unit in Ivory
      Coast. It will permit the realization in routine of these exams and, then, the
      improvement of the breast cancer patient's treatment.

PMID- 18829412
TI  - [Guidelines for the management of dasatinib (Sprycel)-induced side effects in
      chronic myelogenous leukemia and Philadelphia positive acute lymphoblastic
      leukemias].
AB  - Dasatinib (Sprycel) is a new-targeted therapy used since 2005 in the treatment of
      chronic myelogenous leukemia and de novo Philadelphia positive acute
      lymphoblastic leukaemia patients, intolerant or resistant to imatinib. Despite
      its high efficacy in such patients in terms of hematologic, cytogenetic and
      molecular responses, the onset of frequent and sometimes serious side effects
      particularly in advanced phase patients, especially myelosuppressions and pleural
      effusions, may impair optimal administration of the drug. Recently, dasatinib
      dose optimisation in chronic-phase has reduced the incidence of such adverse
      events without modification of the efficacy, however, their optimal overall
      management can efficiently reduce their severity and minimize their impact on
      disease response. Hereby, we attempted to propose a series of guidelines that
      might be of help in daily practice, in order to control properly these side
      effects.

PMID- 18829413
TI  - [Anti-angiogenic treatment in the management of metastatic renal cell carcinoma].
AB  - Anti-angiogenic treatments have recently been incorporated as a milestone in the
      management of metastatic renal cell carcinoma. This retrospective study explores
      this new practice in 94 patients treated by sorafenib, bevacizumab or sunitinib
      in the department of oncology of CHU of Bordeaux in a 32 months period. The
      adverse effects reported are similar than those from prospective trials but for
      some different in frequency or severity. Efficacy of these drugs appeared more
      modest than expected from phase III trials. An objective response rate or
      stabilisation longer than six month was seen in 35% of the patients. Median
      overall survival was 14.1 months (IC 95%: 8.3-18.7 months). Nevertheless, the
      population considered in this study had a worse prognosis with more patients with
      an altered general status (OMS 2 or 3: 13.8%).

PMID- 18829414
TI  - [Continuous training program for technicians handling antineoplastic drugs and
      occupational exposure risk].
AB  - Training and regular evaluation of technicians involved in the preparation of
      antineoplastic agents seems essential to reduce occupational exposure. In this
      way, a continuous training program was established. Technicians were asked to
      prepare a safe simulated liquid cytotoxic drug with a fluorescein solution (10
      mg/L). After, occupational exposure with this solution was simulated. Ultra
      violet light (365 nm) was employed to determine surface contamination. This
      continuous training program is tested and validated with pharmacy technicians.
      All people handling these drugs (physicians, nurses, pharmacy staff) can use this
      program. Short mandatory training courses are stimulating and well appreciated.

PMID- 18829415
TI  - [Merkel cell carcinoma: current diagnosis and treatment].
AB  - We propose herein a review based on literature data about current treatment of
      Merkel cell carcinoma, including new data on adjuvant radiotherapy and sentinel
      lymph node biopsy.

PMID- 18829416
TI  - [Epithelial ovarian tumor microecology].
AB  - Epithelial ovarian cancer remains an insidious and fatal gynecological
      malignancy. They are associated with a poor prognosis mainly due to a late
      diagnosis and to acquired chemoresistance. Cancer cell environment profoundly
      influences tumor development. Tumor microenvironment consists of vascular
      component, stromal fibroblasts, inflammatory cells and extracellular matrix. The
      multisite development of epithelial ovarian cancer results from molecular and
      cellular cross-talks between cancer cells, stromal cells and their extracellular
      matrix environment. These interactions involve cytokines, adhesives molecules,
      and proteolytic systems. This review points out the importance of micro-ecology
      in epithelial ovarian cancer development. For this purpose the relationships
      between cancer cells and their encountered microenvironments are described with
      suggesting some potential therapeutic perspectives.

PMID- 18829417
TI  - [Cancer diagnosis announcement: an act to seal the pact of trust between doctors
      and patients].
AB  - The announcement of the cancer diagnosis, an important moment in the set up of
      the doctor/patient relationship, must come together, if possible, with a quality
      of communication. This announcement is never insignificant, often traumatic both
      for the one who receives it and sometimes for the person who provides it. It must
      observe some rules of temporality, in its enunciation and take into account the
      psychological defences of patient's mechanisms. More accessible, but also more
      complex medical information is supposed to be more transparent, taking into
      account the wishes of patients considered as full actors of their health. As
      such, the announcement of bad news is in a relationship of care, trust represents
      the start of a full therapeutic act. One of the challenges of the diagnosis
      announcement remains the education of patients and physicians to encourage better
      adaptation to the disease and its treatments. This education can only take place
      in a pluridisciplinarity in order to optimize care. The diagnosis announcement
      must continuously oscillate between fair distance and proximity while respecting
      the autonomy, dignity and freedom of patient's choice. The respect of ethical
      principles will prevent incomprehension phenomena and seal the pact of trust
      between doctors and patients.

PMID- 18829418
TI  - [Femininity and breast cancer, original approach of announcement in oncology].
AB  - The measure number 40 of French Plan against Cancer requires taking into
      consideration patient's personality and its effect on social relations. However,
      this psychological impact is different for each cancer. The aim of the present
      study is to discuss the resulting effects after discovery of breast cancer.
      Breast cancer is the most common malignancy in women and it's becomes a greater
      fear of our society. Psychological impact of breast cancer discovery is double:
      first, it is linked to the bad image of cancer which means suffering and death,
      then to the good image of breast, symbol of femininity, sexuality and maternity.
      Considering together these two components can permit to optimize information,
      listening, help and finally adhesion to treatment. And, if the psycho-oncology is
      now essential, tomorrow socio-esthetic will come within the framework of more
      human practice in oncology. Paradoxically, whereas early diagnosis is more
      frequent and its treatment is improved, breast cancer remains an alarming
      disease. So, physician can propose since announcement a best utilization of
      supportive care in order to limit personal and social impact.

PMID- 18829419
TI  - [Psychosocial approach of the speech of women in metastatic relapse of a breast
      cancer: the question of temporality].
AB  - The "relapse", this word so much dreaded by the patients reached of a cancer
      because it symbolizes the return of the disease and the treatments in the
      person's life and his entourage. This diagnosis once established mark the entry
      into a chronic phase of the cancerous disease, involving the future of people and
      their report at time. In this context, we believe it is important to identify the
      subjective and social aspects of the experience of this difficult moment in the
      course of the disease, by taking account the report at the time of the patients.
      In this article, we propose a study of these different aspects through a double
      analysis (lexical thematic manual and with a computer) of semi-structured
      interviews conducted with patients in metastatic relapse of a breast cancer. The
      report at time was operationalized at the same time as a variable of personality
      by using the scale of temporal prospect (PT) Zimbardo Time Perspective Inventory
      ZTPI and through the different linguistic markers, indicators of meaning in the
      stories of patients. The results of this double analysis highlight different
      aspects of the speech of the patients, reflecting investments different in the
      disease at the time of the relapse and and, depending on age and time profiles of
      patients. However, these results illustrate the links between some aspects of
      time focusing on the stories of patients and the strategies of adjustments which
      result from this, allowing an articulation of these concepts around the notion of
      control.

PMID- 18829420
TI  - [The use of deodorants/antiperspirants does not constitute a risk factor for
      breast cancer].
AB  - Based on the observation of a high incidence of breast cancer in the upper outer
      quadrant adjacent to the usual area of application of deodorants and/or
      antiperspirants, several scientific teams have advanced the hypothesis of a
      possible link between antiperspirants and breast cancer. The possibility of the
      involvement of parabens and aluminium salts, traditional components of a number
      of cosmetic products, has been advanced by the same teams. In order to ascertain
      whether this hypothesis could or could not be confirmed, a group of clinical
      experts in oncology was set up to search and analyse the literature data relating
      to the problem raised with the aim of answering three predefined questions: 1)
      does it exist experimental or biological arguments supporting a potential link
      between the use of deodorants/antiperspirants and breast cancer? 2) Does the use
      of deodorants/antiperspirants have any effect on the increase in the risk of
      breast cancer? 3) Could a causal relationship between the use of
      deodorants/antiperspirants and breast cancer be accepted? The scientific data
      were searched systematically in the PubMed database
      (http://www.ncbi.nlm.nih.gov/sites/entrez) using standardised search equations.
      Fifty-nine studies resulting from the literature search were reviewed and
      nineteen articles with various methodologies were selected for in-depth analysis.
      In view of the fact that parabens are generally not present in
      deodorants/antiperspirants, the reflection group's search related purely to the
      question of aluminium salts. Among these nineteen articles, many are
      methodologically unsound, do not answer to the questions posed or deal with the
      question of parabens and were therefore discarded by the reflection group. The
      expert group's conclusion coincides with those of the French, European and
      American health authorities. After analysis of the available literature on the
      subject, no scientific evidence to support the hypothesis was identified and no
      validated hypothesis appears likely to open the way to interesting avenues of
      research.

PMID- 18829421
TI  - [Clinical practice guidelines 2008 for the surgical treatment, medical first-line
      and consolidation treatments of patients with epithelial ovarian cancer--update.
      According to the methodology of Standards, Options: Recommendations (SOR)].
AB  - CONTEXT: Ovarian cancers represent the 4th cause of mortality by cancer for women
      in France and were responsible of more than 3,000 deaths in 2005. The Standards,
      Options: Recommendations (SOR) project has been undertaken by the French National
      Federation of Cancers Centers is now part of the French National Cancer Institute
      since the 1st of may 2008. The project involves the development and updating of
      evidence-based clinical practice guidelines (CPG) in oncology. Following the
      monitoring process, we identified new data conferring sufficient elements to
      justify an updating of the CPG concerning the surgical, the medical fi rst-line
      and consolidation treatments of epithelial ovarian cancers. OBJECTIVES: To update
      the CPG according to the methodology SOR.

PMID- 18829422
TI  - Evaluating timeframe expectancies in physical activity social cognition: are
      short- and long-term motives different?
AB  - Promoting maintenance of regular physical activity (PA) is a public health
      priority; however, to the authors' knowledge, no researchers to date have
      examined whether the expectancies of proximal PA enactment are similar to the
      expectancies of longer maintenance. Thus, the authors' purpose in this study was
      to evaluate whether PA expectancies, measured with constructs of the theory of
      planned behavior (TPB), varied as a function of time frame (no time frame, next
      week, next month, next 6 months). Undergraduate students (N=409) completed
      randomly distributed self-report measures of the TPB; the authors then compared
      results across the 4 groups (formed on the basis of time frame). Analysis of
      variance tests showed that 13 of 37 constructs were significantly (p<.05)
      different, and post hoc follow-up tests identified that the proximal time frame
      (ie, next week) had the significantly lowest mean value. Chi-square tests of
      independent correlations, however, revealed few differences in TPB-intention
      correlations by time frame. The results suggest that social cognitive correlates
      of PA intention are robust to timeframe deviations but that time frame may affect
      the absolute values of some constructs. Overall, this is a positive finding
      because it suggests that PA promotion efforts focused on increasing expectancies
      do not have to be tailored to proximal or more distal maintenance applications.

PMID- 18829423
TI  - How academic psychiatry can better prepare students for their future patients.
      Part I: the failure to recognize depression and risk for suicide in primary care;
      problem identification, responsibility, and solutions.
AB  - The author, after a review of the relevant literature, found that depression and
      the risk for suicide remain unacceptably underrecognized in primary care (PC).
      The negative consequences are substantial for patients and their physicians.
      Suicide prevention in PC begins with the recognition of depression because
      suicide occurs largely during depression. In this article (Part I), the author
      suggests causes, responsibilities, and solutions for that failure. He also
      addresses the role of academic psychiatry's traditional curriculum. The
      comprehensive, initial diagnostic interview that is typically taught to medical
      students in psychiatry may decrease recognition in PC care because of the time
      required to complete it. In Part II, the author offers guidelines to develop a
      weekly interview course with an instrument targeting abbreviated diagnostic
      screening for only the most critical psychiatric problems such as depression and
      the risk for suicide.

PMID- 18829424
TI  - How academic psychiatry can better prepare students for their future patients.
      Part II: a course in ultra-brief initial diagnostic screening suitable for future
      primary care physicians.
AB  - Depression is inadequately treated in primary care (PC), primarily because of a
      failure to recognize symptoms of depression. The results can be catastrophic and
      include death by suicide. The prevention of suicide is a critical function of
      physicians. The recognition of depression is the first step to preventing suicide
      because suicide predominately occurs during depression. The traditional,
      comprehensive psychiatric interview typically taught by academic psychiatry may
      inhibit recognition in PC settings because it takes too much time. Attempts to
      integrate a brief psychiatric interview into the PC-patient interaction to meet
      these needs of increasing recognition have had mixed results. Instruction to
      medical students on psychiatry in the use of an ultra-brief screening instrument
      for these disorders, suitable for the time-pressured PC environment, could help
      attain the goal of improved recognition. A Four-Question, 90-Second Depression
      Screen is described and recommended. The author offers a detailed format for
      establishing an interview course to impart such skills that is appropriate for
      students and residents in their psychiatry or PC rotations.

PMID- 18829425
TI  - Neural correlates of economic game playing.
AB  - The theory of games provides a mathematical formalization of strategic choices,
      which have been studied in both economics and neuroscience, and more recently has
      become the focus of neuroeconomics experiments with human and non-human actors.
      This paper reviews the results from a number of game experiments that establish a
      unitary system for forming subjective expected utility maps in the brain, and
      acting on these maps to produce choices. Social situations require the brain to
      build an understanding of the other person using neuronal mechanisms that share
      affective and intentional mental states. These systems allow subjects to better
      predict other players' choices, and allow them to modify their subjective utility
      maps to value pro-social strategies. New results for a trust game are presented,
      which show that the trust relationship includes systems common to both trusting
      and trustworthy behaviour, but they also show that the relative temporal
      positions of first and second players require computations unique to that role.

PMID- 18829426
TI  - The role of the striatum in aversive learning and aversive prediction errors.
AB  - Neuroeconomic studies of decision making have emphasized reward learning as
      critical in the representation of value-driven choice behaviour. However, it is
      readily apparent that punishment and aversive learning are also significant
      factors in motivating decisions and actions. In this paper, we review the role of
      the striatum and amygdala in affective learning and the coding of aversive
      prediction errors (PEs). We present neuroimaging results showing aversive PE
      related signals in the striatum in fear conditioning paradigms with both primary
      (shock) and secondary (monetary loss) reinforcers. These results and others point
      to the general role for the striatum in coding PEs across a broad range of
      learning paradigms and reinforcer types.

PMID- 18829427
TI  - Neuroethology of reward and decision making.
AB  - Ethology, the evolutionary science of behaviour, assumes that natural selection
      shapes behaviour and its neural substrates in humans and other animals. In this
      view, the nervous system of any animal comprises a suite of morphological and
      behavioural adaptations for solving specific information processing problems
      posed by the physical or social environment. Since the allocation of behaviour
      often reflects economic optimization of evolutionary fitness subject to physical
      and cognitive constraints, neurobiological studies of reward, punishment,
      motivation and decision making will profit from an appreciation of the
      information processing problems confronted by animals in their natural physical
      and social environments.

PMID- 18829428
TI  - Anticipatory affect: neural correlates and consequences for choice.
AB  - 'Anticipatory affect' refers to emotional states that people experience while
      anticipating significant outcomes. Historically, technical limitations have made
      it difficult to determine whether anticipatory affect influences subsequent
      choice. Recent advances in the spatio-temporal resolution of functional magnetic
      resonance imaging, however, now allow researchers to visualize changes in neural
      activity seconds before choice occurs. We review evidence that activation in
      specific brain circuits changes during anticipation of monetary incentives, that
      this activation correlates with affective experience and that activity in these
      circuits may influence subsequent choice. Specifically, an activation likelihood
      estimate meta-analysis of cued response studies indicates that nucleus accumbens
      (NAcc) activation increases during gain anticipation relative to loss
      anticipation, while anterior insula activation increases during both loss and
      gain anticipation. Additionally, anticipatory NAcc activation correlates with
      self-reported positive arousal, whereas anterior insula activation correlates
      with both self-reported negative and positive arousal. Finally, NAcc activation
      precedes the purchase of desirable products and choice of high-risk gambles,
      whereas anterior insula activation precedes the rejection of overpriced products
      and choice of low-risk gambles. Together, these findings support a neurally
      plausible framework for understanding how anticipatory affect can influence
      choice.

PMID- 18829429
TI  - The role of social cognition in decision making.
AB  - Successful decision making in a social setting depends on our ability to
      understand the intentions, emotions and beliefs of others. The mirror system
      allows us to understand other people's motor actions and action intentions.
      'Empathy' allows us to understand and share emotions and sensations with others.
      'Theory of mind' allows us to understand more abstract concepts such as beliefs
      or wishes in others. In all these cases, evidence has accumulated that we use the
      specific neural networks engaged in processing mental states in ourselves to
      understand the same mental states in others. However, the magnitude of the brain
      activity in these shared networks is modulated by contextual appraisal of the
      situation or the other person. An important feature of decision making in a
      social setting concerns the interaction of reason and emotion. We consider four
      domains where such interactions occur: our sense of fairness, altruistic
      punishment, trust and framing effects. In these cases, social motivations and
      emotions compete with each other, while higher-level control processes modulate
      the interactions of these low-level biases.

PMID- 18829430
TI  - Cortical mechanisms for reinforcement learning in competitive games.
AB  - Game theory analyses optimal strategies for multiple decision makers interacting
      in a social group. However, the behaviours of individual humans and animals often
      deviate systematically from the optimal strategies described by game theory. The
      behaviours of rhesus monkeys (Macaca mulatta) in simple zero-sum games showed
      similar patterns, but their departures from the optimal strategies were well
      accounted for by a simple reinforcement-learning algorithm. During a computer
      simulated zero-sum game, neurons in the dorsolateral prefrontal cortex often
      encoded the previous choices of the animal and its opponent as well as the
      animal's reward history. By contrast, the neurons in the anterior cingulate
      cortex predominantly encoded the animal's reward history. Using simple
      competitive games, therefore, we have demonstrated functional specialization
      between different areas of the primate frontal cortex involved in outcome
      monitoring and action selection. Temporally extended signals related to the
      animal's previous choices might facilitate the association between choices and
      their delayed outcomes, whereas information about the choices of the opponent
      might be used to estimate the reward expected from a particular action. Finally,
      signals related to the reward history might be used to monitor the overall
      success of the animal's current decision-making strategy.

PMID- 18829431
TI  - Introduction. Neuroeconomics: the promise and the profit.
AB  - Neuroeconomics investigates the neural mechanisms underlying decisions about
      rewarding or punishing outcomes ('economic' decisions). It combines the knowledge
      about the behavioural phenomena of economic decisions with the mechanistic
      explanatory power of neuroscience. Thus, it is about the neurobiological
      foundations of economic decision making. It is hoped that by 'opening the box' we
      can understand how decisions about gains and losses are directed by the brain of
      the individual decision maker. Perhaps we can even learn why some decisions are
      apparently paradoxical or pathological. The knowledge could be used to create
      situations that avoid suboptimal decisions and harm.

PMID- 18829432
TI  - Intangibility in intertemporal choice.
AB  - Since the advent of the discounted utility (DU) model, economists have thought
      about intertemporal choice in very specific terms. DU assumes that people make
      explicit trade-offs between costs and benefits occurring at different points in
      time. While this explicit trade-off perspective is simple and tractable, and has
      stimulated productive research, it does not provide a very realistic
      representation of a wide range of the most important intertemporal trade-offs
      that people face in daily life. If one considers the most important and commonly
      discussed examples of intertemporal choices, a striking pattern emerges: in
      almost all cases, early outcomes tend to be concrete (e.g. purchasing this
      latte), but later outcomes tend to be much less tangible (e.g. the unknown item
      that could have been purchased later with the money spent on this latte). We
      propose that people rely on anticipatory emotions as a proxy for intangible
      outcomes when trade-offs are implicit. This paper reviews neuroeconomic evidence
      that has begun to elucidate the role of anticipatory emotions in decisions
      involving intangible outcomes. Although most progress has been made in the domain
      of spending and saving, we discuss how the existing neuroeconomic research could
      be extended to other domains where trade-offs are ill defined.

PMID- 18829433
TI  - Explicit neural signals reflecting reward uncertainty.
AB  - The acknowledged importance of uncertainty in economic decision making has
      stimulated the search for neural signals that could influence learning and inform
      decision mechanisms. Current views distinguish two forms of uncertainty, namely
      risk and ambiguity, depending on whether the probability distributions of
      outcomes are known or unknown. Behavioural neurophysiological studies on dopamine
      neurons revealed a risk signal, which covaried with the standard deviation or
      variance of the magnitude of juice rewards and occurred separately from reward
      value coding. Human imaging studies identified similarly distinct risk signals
      for monetary rewards in the striatum and orbitofrontal cortex (OFC), thus
      fulfilling a requirement for the mean variance approach of economic decision
      theory. The orbitofrontal risk signal covaried with individual risk attitudes,
      possibly explaining individual differences in risk perception and risky decision
      making. Ambiguous gambles with incomplete probabilistic information induced
      stronger brain signals than risky gambles in OFC and amygdala, suggesting that
      the brain's reward system signals the partial lack of information. The brain can
      use the uncertainty signals to assess the uncertainty of rewards, influence
      learning, modulate the value of uncertain rewards and make appropriate
      behavioural choices between only partly known options.

PMID- 18829434
TI  - Crystal structure of an extensively simplified variant of bovine pancreatic
      trypsin inhibitor in which over one-third of the residues are alanines.
AB  - We report the high-resolution crystal structures of an extensively simplified
      variant of bovine pancreatic trypsin inhibitor containing 20 alanines (BPTI-20st)
      and a reference single-disulfide-bonded variant (BPTI-[5,55]st) at, respectively,
      1.39 and 1.09 A resolutions. The sequence was simplified based on the results of
      an alanine scanning experiment, as reported previously. The effects of the
      multiple alanine substitutions on the overall backbone structure were
      surprisingly small (C(alpha) atom RMSD of 0.53 A) being limited to small local
      structural perturbations. Both BPTI variants retained a wild-type level of
      trypsin inhibitory activity. The side-chain configurations of residues buried in
      the hydrophobic cores (<30% accessible surface area) were almost perfectly
      retained in both BPTI-20st and BPTI-[5,55]st, indicating that neither multiple
      alanine replacements nor the removal of the disulfide bonds affected their
      precise placements. However, the side chains of three partially buried residues
      (Q31, R20, and to some extent Y21) and several unburied residues rearranged into
      alternative dense-packing structures, suggesting some plasticity in their shape
      complementarity. These results indicate that a protein sequence simplified over
      its entire length can retain its densely packed, native side-chain structure, and
      suggest that both the design and fold recognition of natively folded proteins may
      be easier than previously thought.

PMID- 18829435
TI  - The role of the C terminus of the SNARE protein SNAP-25 in fusion pore opening
      and a model for fusion pore mechanics.
AB  - Formation of a fusion pore between a vesicle and its target membrane is thought
      to involve the so-called SNARE protein complex. However, there is no mechanistic
      model explaining how the fusion pore is opened by conformational changes in the
      SNARE complex. It has been suggested that C-terminal zipping triggers fusion pore
      opening. A SNAP-25 mutant named SNAP-25Delta9 (lacking the last nine C-terminal
      residues) should lead to a less-tight C-terminal zipping. Single exocytotic
      events in chromaffin cells expressing this mutant were characterized by carbon
      fiber amperometry and cell-attached patch capacitance measurements. Cells
      expressing SNAP-25Delta9 displayed smaller amperometric "foot-current" currents,
      reduced fusion pore conductances, and lower fusion pore expansion rates. We
      propose that SNARE/lipid complexes form proteolipid fusion pores. Fusion pores
      involving the SNAP-25Delta9 mutant will be less tightly zipped and may lead to a
      longer fusion pore structure, consistent with the observed decrease of fusion
      pore conductance.

PMID- 18829436
TI  - Histone deacetylase SIRT1 modulates neuronal differentiation by its nuclear
      translocation.
AB  - Neural precursor cells (NPCs) differentiate into neurons, astrocytes, and
      oligodendrocytes in response to intrinsic and extrinsic changes. Notch signals
      maintain undifferentiated NPCs, but the mechanisms underlying the neuronal
      differentiation are largely unknown. We show that SIRT1, an NAD(+)-dependent
      histone deacetylase, modulates neuronal differentiation. SIRT1 was found in the
      cytoplasm of embryonic and adult NPCs and was transiently localized in the
      nucleus in response to differentiation stimulus. SIRT1 started to translocate
      into the nucleus within 10 min after the transfer of NPCs into differentiation
      conditions, stayed in the nucleus, and then gradually retranslocated to the
      cytoplasm after several hours. The number of neurospheres that generated Tuj1(+)
      neurons was significantly decreased by pharmacological inhibitors of SIRT1,
      dominant-negative SIRT1 and SIRT1-siRNA, whereas overexpression of SIRT1, but not
      that of cytoplasm-localized mutant SIRT1, enhanced neuronal differentiation and
      decreased Hes1 expression. Expression of SIRT1-siRNA impaired neuronal
      differentiation and migration of NPCs into the cortical plate in the embryonic
      brain. Nuclear receptor corepressor (N-CoR), which has been reported to bind
      SIRT1, promoted neuronal differentiation and synergistically increased the number
      of Tuj1(+) neurons with SIRT1, and both bound the Hes1 promoter region in
      differentiating NPCs. Hes1 transactivation by Notch1 was inhibited by SIRT1
      and/or N-CoR. Our study indicated that SIRT1 is a player of repressing Notch1
      Hes1 signaling pathway, and its transient translocation into the nucleus may have
      a role in the differentiation of NPCs.

PMID- 18829437
TI  - Single-particle kinetics of influenza virus membrane fusion.
AB  - Membrane fusion is an essential step during entry of enveloped viruses into
      cells. Conventional fusion assays are generally limited to observation of
      ensembles of multiple fusion events, confounding more detailed analysis of the
      sequence of the molecular steps involved. We have developed an in vitro, two
      color fluorescence assay to monitor kinetics of single virus particles fusing
      with a target bilayer on an essentially fluid support. Analysis of lipid- and
      content-mixing trajectories on a particle-by-particle basis provides evidence for
      multiple, long-lived kinetic intermediates leading to hemifusion, followed by a
      single, rate-limiting step to pore formation. We interpret the series of
      intermediates preceding hemifusion as a result of the requirement that multiple
      copies of the trimeric hemagglutinin fusion protein be activated to initiate the
      fusion process.

PMID- 18829438
TI  - The HDAC inhibitor 4b ameliorates the disease phenotype and transcriptional
      abnormalities in Huntington's disease transgenic mice.
AB  - Transcriptional dysregulation has emerged as a core pathologic feature of
      Huntington's disease (HD), one of several triplet-repeat disorders characterized
      by movement deficits and cognitive dysfunction. Although the mechanisms
      contributing to the gene expression deficits remain unknown, therapeutic
      strategies have aimed to improve transcriptional output via modulation of
      chromatin structure. Recent studies have demonstrated therapeutic effects of
      commercially available histone deacetylase (HDAC) inhibitors in several HD
      models; however, the therapeutic value of these compounds is limited by their
      toxic effects. Here, beneficial effects of a novel pimelic diphenylamide HDAC
      inhibitor, HDACi 4b, in an HD mouse model are reported. Chronic oral
      administration of HDACi 4b, beginning after the onset of motor deficits,
      significantly improved motor performance, overall appearance, and body weight of
      symptomatic R6/2(300Q) transgenic mice. These effects were associated with
      significant attenuation of gross brain-size decline and striatal atrophy.
      Microarray studies revealed that HDACi 4b treatment ameliorated, in part,
      alterations in gene expression caused by the presence of mutant huntingtin
      protein in the striatum, cortex, and cerebellum of R6/2(300Q) transgenic mice.
      For selected genes, HDACi 4b treatment reversed histone H3 hypoacetylation
      observed in the presence of mutant huntingtin, in association with correction of
      mRNA expression levels. These findings suggest that HDACi 4b, and possibly
      related HDAC inhibitors, may offer clinical benefit for HD patients and provide a
      novel set of potential biomarkers for clinical assessment.

PMID- 18829439
TI  - Quantitative proteomic analysis of primary neurons reveals diverse changes in
      synaptic protein content in fmr1 knockout mice.
AB  - Fragile X syndrome (FXS) is a common inherited form of mental retardation that is
      caused, in the vast majority of cases, by the transcriptional silencing of a
      single gene, fmr1. The encoded protein, FMRP, regulates mRNA translation in
      neuronal dendrites, and it is thought that changes in translation-dependent forms
      of synaptic plasticity lead to many symptoms of FXS. However, little is known
      about the potentially extensive changes in synaptic protein content that
      accompany loss of FMRP. Here, we describe the development of a high-throughput
      quantitative proteomic method to identify differences in synaptic protein
      expression between wild-type and fmr1-/- mouse cortical neurons. The method is
      based on stable isotope labeling by amino acids in cell culture (SILAC), which
      has been used to characterize differentially expressed proteins in dividing
      cells, but not in terminally differentiated cells because of reduced labeling
      efficiency. To address the issue of incomplete labeling, we developed a
      mathematical method to normalize protein ratios relative to a reference based on
      the labeling efficiency. Using this approach, in conjunction with
      multidimensional protein identification technology (MudPIT), we identified >100
      proteins that are up- or down-regulated. These proteins fall into a variety of
      functional categories, including those regulating synaptic structure,
      neurotransmission, dendritic mRNA transport, and several proteins implicated in
      epilepsy and autism, two endophenotypes of FXS. These studies provide insights
      into the potential origins of synaptic abnormalities in FXS and a demonstration
      of a methodology that can be used to explore neuronal protein changes in
      neurological disorders.

PMID- 18829440
TI  - Structure and DNA binding of alkylation response protein AidB.
AB  - Exposure of Escherichia coli to alkylating agents activates expression of AidB in
      addition to DNA repair proteins Ada, AlkA, and AlkB. AidB was recently shown to
      possess a flavin adenine dinucleotide (FAD) cofactor and to bind to dsDNA,
      implicating it as a flavin-dependent DNA repair enzyme. However, the molecular
      mechanism by which AidB acts to reduce the mutagenic effects of specific DNA
      alkylators is unknown. We present a 1.7-A crystal structure of AidB, which bears
      superficial resemblance to the acyl-CoA dehydrogenase superfamily of
      flavoproteins. The structure reveals a unique quaternary organization and a
      distinctive FAD active site that provides a rationale for AidB's limited
      dehydrogenase activity. A highly electropositive C-terminal domain not present in
      structural homologs was identified by mutational analysis as the DNA binding
      site. Structural analysis of the DNA and FAD binding sites provides evidence
      against AidB-catalyzed DNA repair and supports a model in which AidB acts to
      prevent alkylation damage by protecting DNA and destroying alkylating agents that
      have yet to reach their DNA target.

PMID- 18829441
TI  - Energetics of peptide (pHLIP) binding to and folding across a lipid bilayer
      membrane.
AB  - The pH low-insertion peptide (pHLIP) serves as a model system for peptide
      insertion and folding across a lipid bilayer. It has three general states: (I)
      soluble in water or (II) bound to the surface of a lipid bilayer as an
      unstructured monomer, and (III) inserted across the bilayer as a monomeric alpha
      helix. We used fluorescence spectroscopy and isothermal titration calorimetry to
      study the interactions of pHLIP with a palmitoyloleoylphosphatidylcholine (POPC)
      lipid bilayer and to calculate the transition energies between states. We found
      that the Gibbs free energy of binding to a POPC surface at low pHLIP
      concentration (state I-state II transition) at 37 degrees C is approximately -7
      kcal/mol near neutral pH and that the free energy of insertion and folding across
      a lipid bilayer at low pH (state II-state III transition) is nearly -2 kcal/mol.
      We discuss a number of related thermodynamic parameters from our measurements.
      Besides its fundamental interest as a model system for the study of membrane
      protein folding, pHLIP has utility as an agent to target diseased tissues and
      translocate molecules through the membrane into the cytoplasm of cells in
      environments with elevated levels of extracellular acidity, as in cancer and
      inflammation. The results give the amount of energy that might be used to move
      cargo molecules across a membrane.

PMID- 18829442
TI  - Blood-brain barrier changes and cell invasion differ between therapeutic immune
      clearance of neurotrophic virus and CNS autoimmunity.
AB  - CNS tissues are protected from circulating cells and factors by the blood-brain
      barrier (BBB), a specialization of the neurovasculature. Outcomes of the loss of
      BBB integrity and cell infiltration into CNS tissues can differ vastly. For
      example, elevated BBB permeability is closely associated with the development of
      neurological disease in experimental allergic encephalomyelitis (EAE) but not
      during clearance of the attenuated rabies virus CVS-F3 from the CNS tissues. To
      probe whether differences in the nature of BBB permeability changes may
      contribute to the pathogenesis of acute neuroinflammatory disease, we compared
      the characteristics of BBB permeability changes in mice with EAE and in mice
      clearing CVS-F3. BBB permeability changes are largely restricted to the
      cerebellum and spinal cord in both models but differ in the extent of leakage of
      markers of different size and in the nature of cell accumulation in the CNS
      tissues. The accumulation in the CNS tissues of CD4 T cells expressing mRNAs
      specific for IFN-gamma and IL-17 is common to both, but iNOS-positive cells
      invade into the CNS parenchyma only in EAE. Mice that have been immunized with
      myelin basic protein (MBP) and infected exhibit the features of EAE. Treatment
      with the peroxynitrite-dependent radical scavenger urate inhibits the invasion of
      iNOS-positive cells into the CNS tissues and the development of clinical signs of
      EAE without preventing the loss of BBB integrity in immunized/infected animals.
      These findings indicate that BBB permeability changes can occur in the absence of
      neuropathology provided that cell invasion is restricted.

PMID- 18829443
TI  - The effect of hand acupuncture therapy and hand moxibustion therapy on
      premenstrual syndrome among Korean women.
AB  - Premenstrual syndrome (PMS) symptoms can reduce quality of life and impair daily
      functioning. This study examined the effects of Korean hand acupuncture therapy
      (HAT) and hand moxibustion therapy (HMT) on symptom severity in Korean women with
      PMS. This quasi-experimental pilot study based on the khi, yin, yang, and the
      five elements theory used a nonequivalent control group pretest-posttest design.
      Experimental groups received 10 sessions of either HAT or HMT treatment. Outcome
      measures included menstrual symptom severity as measured with the Menstrual
      Symptom Severity List and skin temperature change measured with Digital Infrared
      Thermographic Imaging. Both experimental groups had significantly reduced overall
      PMS symptom severity scores following therapy as compared to women in the control
      group. The HMT but not the HAT group showed improved flow of khi and balanced
      skin temperature in symmetric body areas. HAT and HMT may be effective strategies
      for women to reduce PMS symptoms.

PMID- 18829445
TI  - Congenital abnormalities and acute leukemia among children with Down syndrome: a
      Children's Oncology Group study.
AB  - Children with Down syndrome, due to their heightened risk of leukemia and
      increased prevalence of congenital abnormalities, comprise a valuable population
      in which to study etiology. A Children's Oncology Group study investigated the
      causes of childhood leukemia in children with Down syndrome diagnosed at ages 0
      to 19 years during the period 1997-2002. Telephone interviews were completed with
      mothers of 158 cases [n=97 acute lymphoblastic leukemia (ALL) and n=61 acute
      myeloid leukemia (AML)] and 173 controls. Odds ratios (OR) and 95% confidence
      intervals (95% CI) were computed via unconditional logistic regression to
      evaluate the association between congenital abnormalities and acute leukemia
      overall, and ALL and AML analyzed separately. The results do not provide evidence
      for an association among the index children (OR(Combined), 0.74; 95% CI, 0.45
      1.23; OR(ALL), 0.67; 95% CI, 0.38-1.20; OR(AML),1.03; 95% CI, 0.49-2.16) or their
      siblings (OR(Combined), 1.23; 95% CI, 0.71-2.13; OR(ALL), 1.12; 95% CI, 0.60
      2.09; OR(AML), 1.60; 95% CI, 0.66-3.86), suggesting congenital malformations do
      not confer additional risk of leukemia beyond the risk attributable to trisomy 21
      in this population.

PMID- 18829446
TI  - Explaining the race difference in prostate cancer stage at diagnosis.
AB  - Prostate cancer is the most frequently diagnosed cancer in males in the United
      States, accounting for an estimated 186,320 new cases in 2008. There are striking
      racial or ethnic differences in prostate cancer incidence and mortality rates in
      the United States, with Black males 1.6 times more likely to be diagnosed and 2.4
      times more likely to die with prostate cancer than Whites. Stage at diagnosis is
      a key prognostic factor for prostate cancer survival, with African-Americans
      generally diagnosed at a more advanced stage. To identify factors that explain
      the race-stage disparity in prostate cancer, we conducted a population-based case
      case study of 251 African-American (46%) and White (54%) prostate cancer cases
      diagnosed in Connecticut between January 1987 and October 1990. Multivariate
      logistic regression was used to identify potential explanatory factors, including
      clinical, sociodemographic, medical care, insurance, digital rectal examination
      screening history, and lifestyle factors. Cox proportional hazards models
      assessed the impact of study variables on race differences in long-term survival.
      Modifiable factors such as screening practice and sociodemographic factors
      accounted for >60% of the race difference in prostate cancer stage at diagnosis.
      Histologic grade (Gleason score) accounted for comparatively less. Survival
      analyses confirmed the importance of tumor characteristics, education, and
      insurance in explaining observed race differences in survival. Although cases
      were identified before the widespread use of prostate-specific antigen (PSA)
      screening, the results should also be relevant to countries that have large
      underserved populations and/or disparities in access to medical care and cancer
      screening.

PMID- 18829444
TI  - Conjugated equine estrogens and colorectal cancer incidence and survival: the
      Women's Health Initiative randomized clinical trial.
AB  - BACKGROUND: In separate Women's Health Initiative randomized trials, combined
      hormone therapy with estrogen plus progestin reduced colorectal cancer incidence
      but estrogen alone in women with hysterectomy did not. We now analyze features of
      the colorectal cancers that developed and examine the survival of women following
      colorectal cancer diagnosis in the latter trial. PARTICIPANTS AND METHODS: 10,739
      postmenopausal women who were 50 to 79 years of age and had undergone
      hysterectomy were randomized to conjugated equine estrogens (0.625 mg/d) or
      matching placebo. Colorectal cancer incidence was a component of the monitoring
      global index of the study but was not a primary study endpoint. Colorectal
      cancers were verified by central medical record and pathology report review.
      Bowel exam frequency was not protocol defined, but information on their use was
      collected. RESULTS: After a median 7.1 years, there were 58 invasive colorectal
      cancers in the hormone group and 53 in the placebo group [hazard ratio, 1.12; 95%
      confidence interval (95% CI), 0.77-1.63]. Tumor size, stage, and grade were
      comparable in the two randomization groups. Bowel exam frequency was also
      comparable in the two groups. The cumulative mortality following colorectal
      cancer diagnosis among women in the conjugated equine estrogen group was 34%
      compared with 30% in the placebo group (hazard ratio, 1.34; 95% CI, 0.58-3.19).
      CONCLUSIONS: In contrast to the preponderance of observational studies,
      conjugated equine estrogens in a randomized clinical trial did not reduce
      colorectal cancer incidence nor improve survival after diagnosis.

PMID- 18829447
TI  - Calpain5 expression is decreased in endometriosis and regulated by HOXA10 in
      human endometrial cells.
AB  - Calpains have been implicated in the regulation of apoptosis. Here, we identified
      Calpain5 as a target of HOXA10 transcriptional regulation in endometrial cells as
      well as its aberrant regulation in endometriosis. Histologically confirmed
      biopsies of endometriosis were obtained from 20 women. Eutopic endometrium was
      collected by endometrial biopsy from 30 controls and from the 20 subjects with
      endometriosis. First trimester decidual samples were obtained from five subjects
      at the time of pregnancy termination. Immunohistochemistry was used to identify
      Calpain5 expression. Calpain5 was expressed in endometrial stromal and glandular
      cells throughout the menstrual cycle and in decidua. Calpain5 protein expression
      was decreased in both stromal and glandular cells from women with endometriosis
      compared with that of fertile controls. Human endometrial stromal and epithelial
      cell lines were transfected with pcDNA/HOXA10, HOXA10 siRNA or respective
      controls. Quantitative real-time RT-PCR was performed to determine expression of
      HOXA10 and Calpain5 in each group. Transfection of HESC cells with an HOXA10
      expression construct led to increased Calpain5 expression, whereas transfection
      with siRNA resulted in decreased expression. In conclusion, Calpain5 expression
      is regulated by HOXA10. Calpain5 expression was decreased in endometriosis likely
      as a result of decreased HOXA10 expression. Decreased apoptosis in endometrial
      cells may promote the development of endometriosis through a pathway involving
      HOXA10, Calpain5 and caspase.

PMID- 18829448
TI  - Expression of epithelial cadherin in the human male reproductive tract and
      gametes and evidence of its participation in fertilization.
AB  - Epithelial cadherin (E-cadherin) has been involved in several calcium-dependent
      cell-cell adhesion events; however, its participation in gamete interaction has
      not been fully investigated. Our results have demonstrated expression of E
      cadherin mRNA in the human male reproductive tract showing higher levels in the
      caput, corpus and cauda epididymis than in the testis. The mature 122 kDa E
      cadherin was detected in epididymal protein extracts and was localized in the
      epithelial cells from the three epididymal regions. Moreover, the 86 kDa E
      cadherin ectodomain was found in cauda epididymal and seminal plasma. Western
      immunoblotting of human sperm protein extracts allowed the identification of four
      E-cadherin forms (122, 105, 97 and 86 kDa). The protein was localized in the
      acrosomal region of intact spermatozoa, remained associated with the head of
      acrosome-reacted cells and was also detected on the oocyte surface. A similar
      localization was determined for other proteins of the adhesion complex (beta
      catenin and actin). Spermatozoa incubated with anti-E-cadherin antibodies showed
      impaired binding to homologous zona pellucida (ZP); in addition, presence of
      these antibodies inhibited the penetration of human spermatozoa to ZP-free
      hamster oocytes. The results presented here describe the expression of E-cadherin
      in the male reproductive tract and gametes and strongly suggest its involvement
      in adhesion events during human fertilization. The identification of proteins
      involved in gamete interaction will contribute to the understanding of the
      molecular basis of fertilization and help in the diagnosis and treatment of
      infertility.

PMID- 18829449
TI  - Antibody library selection by the {beta}-lactamase protein fragment
      complementation assay.
AB  - Protein fragment complementation assay (PCA) is based on the interaction between
      two protein partners (e.g. target antigen and antibody), which are genetically
      fused to the two halves of a dissected marker protein. Binding of the two
      partners reassembles the marker protein and hence reconstitutes its activity. In
      this work we have developed the first application of beta-lactamase-based PCA for
      the isolation of single chain Fv fragments (scFvs) binding to the human receptor
      RON from a naive library. Specific scFvs with the ability to immunoprecipitate
      could be isolated after a single round of PCA selection from an scFv repertoire
      previously pre-selected by phage display. Furthermore, the PCA was used to
      successfully map the epitopes recognized by the selected scFvs by screening them
      against a small library of random RON fragments.

PMID- 18829450
TI  - The solution structure of DNA-free Pax-8 paired box domain accounts for redox
      regulation of transcriptional activity in the pax protein family.
AB  - Pax-8 is a transcription factor belonging to the PAX genes superfamily and its
      crucial role has been proven both in embryo and in the adult organism. Pax-8
      activity is regulated via a redox-based mechanism centered on the
      glutathionylation of specific cysteines in the N-terminal region (Cys45 and
      Cys57). These residues belong to a highly evolutionary conserved DNA binding
      site: the Paired Box (Prd) domain. Crystallographic protein-DNA complexes of the
      homologues Pax-6 and Pax-5 showed a bipartite Prd domain consisting of two helix
      turn-helix (HTH) motifs separated by an extended linker region. Here, by means of
      nuclear magnetic resonance, we show for the first time that the HTH motifs are
      largely defined in the unbound Pax-8 Prd domain. Our findings contrast with
      previous induced fit models, in which Pax-8 is supposed to largely fold upon DNA
      binding. Importantly, our data provide the structural basis for the enhanced
      chemical reactivity of residues Cys45 and Cys57 and explain clinical missense
      mutations that are not obviously related to the DNA binding interface of the
      paired box domain. Finally, sequence conservation suggests that our findings
      could be a general feature of the Pax family transcription factors.

PMID- 18829451
TI  - The crystal structure of Desulfovibrio vulgaris dissimilatory sulfite reductase
      bound to DsrC provides novel insights into the mechanism of sulfate respiration.
AB  - Sulfate reduction is one of the earliest types of energy metabolism used by
      ancestral organisms to sustain life. Despite extensive studies, many questions
      remain about the way respiratory sulfate reduction is associated with energy
      conservation. A crucial enzyme in this process is the dissimilatory sulfite
      reductase (dSiR), which contains a unique siroheme-[4Fe4S] coupled cofactor.
      Here, we report the structure of desulfoviridin from Desulfovibrio vulgaris, in
      which the dSiR DsrAB (sulfite reductase) subunits are bound to the DsrC protein.
      The alpha(2)beta(2)gamma(2) assembly contains two siroheme-[4Fe4S] cofactors
      bound by DsrB, two sirohydrochlorins and two [4Fe4S] centers bound by DsrA, and
      another four [4Fe4S] centers in the ferredoxin domains. A sulfite molecule,
      coordinating the siroheme, is found at the active site. The DsrC protein is bound
      in a cleft between DsrA and DsrB with its conserved C-terminal cysteine reaching
      the distal side of the siroheme. We propose a novel mechanism for the process of
      sulfite reduction involving DsrAB, DsrC, and the DsrMKJOP membrane complex (a
      membrane complex with putative disulfide/thiol reductase activity), in which two
      of the six electrons for reduction of sulfite derive from the membrane quinone
      pool. These results show that DsrC is involved in sulfite reduction, which
      changes the mechanism of sulfate respiration. This has important implications for
      models used to date ancient sulfur metabolism based on sulfur isotope
      fractionations.

PMID- 18829452
TI  - Specificity of interactions between mDia isoforms and Rho proteins.
AB  - Formins are key regulators of actin nucleation and polymerization. They contain
      formin homology 1 (FH1) and 2 (FH2) domains as the catalytic machinery for the
      formation of linear actin cables. A subclass of formins constitutes the
      Diaphanous-related formins, members of which are regulated by the binding of a
      small GTP-binding protein of the Rho subfamily. Binding of these molecular switch
      proteins to the regulatory N-terminal mDia(N), including the GTPase-binding
      domain, leads to the release of auto-inhibition. From the three mDia isoforms,
      mDia1 is activated only by Rho (RhoA, -B, and -C), in contrast to mDia2 and -3,
      which is also activated by Rac and Cdc42. Little is known about the determinants
      of specificity. Here we report on the interactions of RhoA, Rac1, and Cdc42 with
      mDia1 and an mDia1 mutant (mDia(N)-Thr-Ser-His (TSH)), which based on structural
      information should mimic mDia2 and -3. Specificity is analyzed by biochemical
      studies and a structural analysis of a complex between Cdc42.Gpp(NH)p and mDia(N)
      TSH. A triple NNN motif in mDia1 (amino acids 164-166), corresponding to the TSH
      motif in mDia2/3 (amino acids 183-185 and 190-192), and the epitope interacting
      with the Rho insert helix are essential for high affinity binding. The triple N
      motif of mDia1 allows tight interaction with Rho because of the presence of Phe
      106, whereas the corresponding His-104 in Rac and Cdc42 forms a complementary
      interface with the TSH motif in mDia2/3. We also show that the F106H and H104F
      mutations drastically alter the affinities and thermodynamics of mDia
      interactions.

PMID- 18829453
TI  - IRBIT, inositol 1,4,5-triphosphate (IP3) receptor-binding protein released with
      IP3, binds Na+/H+ exchanger NHE3 and activates NHE3 activity in response to
      calcium.
AB  - Calcium (Ca2+) is a highly versatile second messenger that regulates various
      cellular processes. Previous studies showed that elevation of intracellular Ca2+
      regulates the activity of Na+/H+ exchanger 3 (NHE3). However, the effect of Ca2+
      dependent signaling on NHE3 activity varies depending on cell types. In this
      study, we report the identification of IP3 receptor-binding protein released with
      IP3 (IRBIT) as a NHE3 interacting protein and its role in regulation of NHE3
      activity. IRBIT bound to the carboxyl-terminal domain of NHE3, which is necessary
      for acute regulation of NHE3. Ectopic expression of IRBIT resulted in Ca2+
      dependent activation of NHE3 activity, whereas silencing of endogenous IRBIT
      resulted in inhibition of NHE3 activity. Ca2+-dependent stimulation of NHE3
      activity was dependent on the binding of IRBIT to NHE3. Previously Ca2+-dependent
      inhibition of NHE3 was demonstrated in the presence of NHERF2. Co-expression of
      IRBIT was able to reverse the NHERF2-dependent inhibition of NHE3. We also showed
      that IRBIT-dependent activation of NHE3 involves exocytic trafficking of NHE3 to
      the plasma membrane and this activation was blocked by inhibition of calmodulin
      (CaM) or CaM-dependent kinase II. These results suggest that the overall effect
      of Ca2+ on NHE3 activity is balanced by IRBIT-dependent activation and NHERF2
      dependent inhibition.

PMID- 18829454
TI  - Potent and selective disruption of protein kinase D functionality by a
      benzoxoloazepinolone.
AB  - Protein kinase D (PKD) is a novel family of serine/threonine kinases targeted by
      the second messenger diacylglycerol. It has been implicated in many important
      cellular processes and pathological conditions. However, further analysis of PKD
      in these processes is severely hampered by the lack of a PKD-specific inhibitor
      that can be readily applied to cells and in animal models. We now report the
      discovery of the first potent and selective cell-active small molecule inhibitor
      for PKD, benzoxoloazepinolone (CID755673). This inhibitor was identified from the
      National Institutes of Health small molecule repository library of 196,173
      compounds using a human PKD1 (PKCmu)-based fluorescence polarization high
      throughput screening assay. CID755673 suppressed half of the PKD1 enzyme activity
      at 182 nm and exhibited selective PKD1 inhibition when compared with AKT, polo
      like kinase 1 (PLK1), CDK activating kinase (CAK), CAMKIIalpha, and three
      different PKC isoforms. Moreover, it was not competitive with ATP for enzyme
      inhibition. In cell-based assays, CID755673 blocked phorbol ester-induced
      endogenous PKD1 activation in LNCaP cells in a concentration-dependent manner.
      Functionally, CID755673 inhibited the known biological actions of PKD1 including
      phorbol ester-induced class IIa histone deacetylase 5 nuclear exclusion,
      vesicular stomatitis virus glycoprotein transport from the Golgi to the plasma
      membrane, and the ilimaquinone-induced Golgi fragmentation. Moreover, CID755673
      inhibited prostate cancer cell proliferation, cell migration, and invasion. In
      summary, our findings indicate that CID755673 is a potent and selective PKD1
      inhibitor with valuable pharmacological and cell biological potential.

PMID- 18829455
TI  - Structural basis of the migfilin-filamin interaction and competition with
      integrin beta tails.
AB  - A link between sites of cell adhesion and the cytoskeleton is essential for
      regulation of cell shape, motility, and signaling. Migfilin is a recently
      identified adaptor protein that localizes at cell-cell and cell-extracellular
      matrix adhesion sites, where it is thought to provide a link to the cytoskeleton
      by interacting with the actin cross-linking protein filamin. Here we have used x
      ray crystallography, NMR spectroscopy, and protein-protein interaction studies to
      investigate the molecular basis of migfilin binding to filamin. We report that
      the N-terminal portion of migfilin can bind all three human filamins (FLNa, -b,
      or -c) and that there are multiple migfilin-binding sites in FLNa. Human filamins
      are composed of an N-terminal actin-binding domain followed by 24 immunoglobulin
      like (IgFLN) domains and we find that migfilin binds preferentially to IgFLNa21
      and more weakly to IgFLNa19 and -22. The filamin-binding site in migfilin is
      localized between Pro(5) and Pro(19) and binds to the CD face of the IgFLNa21
      beta-sandwich. This interaction is similar to the previously characterized beta 7
      integrin-IgFLNa21 interaction and migfilin and integrin beta tails can compete
      with one another for binding to IgFLNa21. This suggests that competition between
      filamin ligands for common binding sites on IgFLN domains may provide a general
      means of modulating filamin interactions and signaling. In this specific case,
      displacement of integrin tails from filamin by migfilin may provide a mechanism
      for switching between different integrin-cytoskeleton linkages.

PMID- 18829456
TI  - Unchanged beta-adrenergic stimulation of cardiac L-type calcium channels in Ca v
      1.2 phosphorylation site S1928A mutant mice.
AB  - Phosphorylation of serine 1928 (Ser(1928)) of the cardiac Ca(v)1.2 subunit of L
      type Ca(2+) channels has been proposed as the mechanism for regulation of L-type
      Ca(2+) channels by protein kinase A (PKA). To test this directly in vivo, we
      generated a knock-in mouse with targeted mutation of Ser(1928) to alanine. This
      mutation did not affect basal L-type current characteristics or regulation of the
      L-type current by PKA and the beta-adrenergic receptor, whereas the mutation
      abolished phosphorylation of Ca(v)1.2 by PKA. Therefore, our data show that PKA
      phosphorylation of Ser(1928) of Ca(v)1.2 is not functionally involved in beta
      adrenergic stimulation of Ca(v)1.2-mediated Ca(2+) influx into the cardiomyocyte.

PMID- 18829457
TI  - A conserved arginine-containing motif crucial for the assembly and enzymatic
      activity of the mixed lineage leukemia protein-1 core complex.
AB  - The mixed lineage leukemia protein-1 (MLL1) belongs to the SET1 family of histone
      H3 lysine 4 methyltransferases. Recent studies indicate that the catalytic
      subunits of SET1 family members are regulated by interaction with a conserved
      core group of proteins that include the WD repeat protein-5 (WDR5),
      retinoblastoma-binding protein-5 (RbBP5), and the absent small homeotic-2-like
      protein (Ash2L). It has been suggested that WDR5 functions to bridge the
      interactions between the catalytic and regulatory subunits of SET1 family
      complexes. However, the molecular details of these interactions are unknown. To
      gain insight into the interactions among these proteins, we have determined the
      biophysical basis for the interaction between the human WDR5 and MLL1. Our
      studies reveal that WDR5 preferentially recognizes a previously unidentified and
      conserved arginine-containing motif, called the "Win" or WDR5 interaction motif,
      which is located in the N-SET region of MLL1 and other SET1 family members.
      Surprisingly, our structural and functional studies show that WDR5 recognizes
      arginine 3765 of the MLL1 Win motif using the same arginine binding pocket on
      WDR5 that was previously shown to bind histone H3. We demonstrate that WDR5's
      recognition of arginine 3765 of MLL1 is essential for the assembly and enzymatic
      activity of the MLL1 core complex in vitro.

PMID- 18829458
TI  - Structural basis of natural promoter recognition by a unique nuclear receptor,
      HNF4alpha. Diabetes gene product.
AB  - HNF4alpha (hepatocyte nuclear factor 4alpha) plays an essential role in the
      development and function of vertebrate organs, including hepatocytes and
      pancreatic beta-cells by regulating expression of multiple genes involved in
      organ development, nutrient transport, and diverse metabolic pathways. As such,
      HNF4alpha is a culprit gene product for a monogenic and dominantly inherited form
      of diabetes, known as maturity onset diabetes of the young (MODY). As a unique
      member of the nuclear receptor superfamily, HNF4alpha recognizes target genes
      containing two hexanucleotide direct repeat DNA-response elements separated by
      one base pair (DR1) by exclusively forming a cooperative homodimer. We describe
      here the 2.0 angstroms crystal structure of human HNF4alpha DNA binding domain in
      complex with a high affinity promoter element of another MODY gene, HNF1alpha,
      which reveals the molecular basis of unique target gene selection/recognition,
      DNA binding cooperativity, and dysfunction caused by diabetes-causing mutations.
      The predicted effects of MODY mutations have been tested by a set of biochemical
      and functional studies, which show that, in contrast to other MODY gene products,
      the subtle disruption of HNF4alpha molecular function can cause significant
      effects in afflicted MODY patients.

PMID- 18829459
TI  - Structure of WDR5 bound to mixed lineage leukemia protein-1 peptide.
AB  - The mixed lineage leukemia protein-1 (MLL1) catalyzes histone H3 lysine 4
      methylation and is regulated by interaction with WDR5 (WD-repeat protein-5),
      RbBP5 (retinoblastoma-binding protein-5), and the Ash2L (absent, small, homeotic
      discs-2-like) oncoprotein. In the accompanying investigation, we describe the
      identification of a conserved arginine containing motif, called the "Win" or WDR5
      interaction motif, that is essential for the assembly and H3K4 dimethylation
      activity of the MLL1 core complex. Here we present a 1.7-A crystal structure of
      WDR5 bound to a peptide derived from the MLL1 Win motif. Our results show that
      Arg-3765 of MLL1 is bound in the same arginine binding pocket on WDR5 that was
      previously suggested to bind histone H3. Thermodynamic binding experiments show
      that the MLL1 Win peptide is preferentially recognized by WDR5. These results are
      consistent with a model in which WDR5 recognizes Arg-3765 of MLL1, which is
      essential for the assembly and enzymatic activity of the MLL1 core complex.

PMID- 18829460
TI  - TAK1-binding protein 1, TAB1, mediates osmotic stress-induced TAK1 activation but
      is dispensable for TAK1-mediated cytokine signaling.
AB  - TAK1 kinase is an indispensable intermediate in several cytokine signaling
      pathways including tumor necrosis factor, interleukin-1, and transforming growth
      factor-beta signaling pathways. TAK1 also participates in stress-activated
      intracellular signaling pathways such as osmotic stress signaling pathway. TAK1
      binding protein 1 (TAB1) is constitutively associated with TAK1 through its C
      terminal region. Although TAB1 is known to augment TAK1 catalytic activity when
      it is overexpressed, the role of TAB1 under physiological conditions has not yet
      been identified. In this study, we determined the role of TAB1 in TAK1 signaling
      by analyzing TAB1-deficient mouse embryonic fibroblasts (MEFs). Tumor necrosis
      factor- and interleukin-1-induced activation of TAK1 was entirely normal in Tab1
      deficient MEFs and could activate both mitogen-activated protein kinases and NF
      kappaB. In contrast, we found that osmotic stress-induced activation of TAK1 was
      largely impaired in Tab1-deficient MEFs. Furthermore, we showed that the C
      terminal 68 amino acids of TAB1 were sufficient to mediate osmotic stress-induced
      TAK1 activation. Finally, we attempted to determine the mechanism by which TAB1
      activates TAK1. We found that TAK1 is spontaneously activated when the
      concentration is increased and that it is totally dependent on TAB1. Cell
      shrinkage under the osmotic stress condition increases the concentration of TAB1
      TAK1 and may oligomerize and activate TAK1 in a TAB1-dependent manner. These
      results demonstrate that TAB1 mediates TAK1 activation only in a subset of TAK1
      pathways that are mediated through spontaneous oligomerization of TAB1-TAK1.

PMID- 18829461
TI  - Phosphatase PPM1A regulates phosphorylation of Thr-186 in the Cdk9 T-loop.
AB  - Cdk9 is the catalytic subunit of a general RNA polymerase II elongation factor
      known as positive transcription elongation factor b (P-TEFb). The kinase function
      of P-TEFb requires phosphorylation of Thr-186 in the T-loop of Cdk9 to allow
      substrates to access the catalytic core of the enzyme. To identify human
      phosphatases that dephosphorylate the T-loop of Cdk9, we used a Thr-186
      phosphospecific antiserum to screen a phosphatase expression library.
      Overexpression of PPM1A and the related PPM1B greatly reduced Cdk9 T-loop
      phosphorylation in vivo. PPM1A and Cdk9 appear to associate in vivo as the
      proteins could be co-immunoprecipitated. The short hairpin RNA depletion of PPM1A
      resulted in an increase in Cdk9 T-loop phosphorylation. In phosphatase reactions
      in vitro, purified PPM1A could dephosphorylate Thr-186 both with and without the
      association of 7SK RNA, a small nuclear RNA that is bound to approximately 50% of
      total cellular P-TEFb. PPM1B only efficiently dephosphorylated Cdk9 Thr-186 in
      vitro when 7SK RNA was depleted from P-TEFb. Taken together, our data indicate
      that PPM1A and to some extent PPM1B are important negative regulators of P-TEFb
      function.

PMID- 18829462
TI  - Isolation of intrinsically active (MEK-independent) variants of the ERK family of
      mitogen-activated protein (MAP) kinases.
AB  - MAPKs are key components of cell signaling pathways with a unique activation
      mechanism: i.e. dual phosphorylation of neighboring threonine and tyrosine
      residues. The ERK enzymes form a subfamily of MAPKs involved in proliferation,
      differentiation, development, learning, and memory. The exact role of each Erk
      molecule in these processes is not clear. An efficient strategy for addressing
      this question is to activate individually each molecule, for example, by
      expressing intrinsically active variants of them. However, such molecules were
      not produced so far. Here, we report on the isolation, via a specifically
      designed genetic screen, of six variants (each carries a point mutation) of the
      yeast MAPK Mpk1/Erk that are active, independent of upstream phosphorylation. One
      of the activating mutations, R68S, occurred in a residue conserved in the
      mammalian Erk1 (Arg-84) and Erk2 (Arg-65) and in the Drosophila ERK Rolled (Arg
      80). Replacing this conserved Arg with Ser rendered these MAPKs intrinsically
      active to very high levels when tested in vitro as recombinant proteins.
      Combination of the Arg to Ser mutation with the sevenmaker mutation (producing
      Erk2(R65S+D319N) and Rolled(R80S+D334N)) resulted in even higher activity (45 and
      70%, respectively, in reference to fully active dually phosphorylated Erk2 or
      Rolled). Erk2(R65S) and Erk2(R65S+D319N) were found to be spontaneously active
      also when expressed in human HEK293 cells. We further revealed the mechanism of
      action of the mutants and show that it involves acquisition of
      autophosphorylation activity. Thus, a first generation of Erk molecules that are
      spontaneously active in vitro and in vivo has been obtained.

PMID- 18829463
TI  - Distinct pharmacological effects of inhibitors of signal peptide peptidase and
      gamma-secretase.
AB  - Signal peptide peptidase (SPP) and gamma-secretase are intramembrane aspartyl
      proteases that bear similar active site motifs but with opposite membrane
      topologies. Both proteases are inhibited by the same aspartyl protease transition
      state analogue inhibitors, further evidence that these two enzymes have the same
      basic cleavage mechanism. Here we report that helical peptide inhibitors designed
      to mimic SPP substrates and interact with the SPP initial substrate-binding site
      (the "docking site") inhibit both SPP and gamma-secretase, but with submicromolar
      potency for SPP. SPP was labeled by helical peptide and transition-state analogue
      affinity probes but at distinct sites. Nonsteroidal anti-inflammatory drugs,
      which shift the site of proteolysis by SPP and gamma-secretase, did not affect
      the labeling of SPP or gamma-secretase by the helical peptide or transition-state
      analogue probes. On the other hand, another class of previously reported gamma
      secretase modulators, naphthyl ketones, inhibited SPP activity as well as
      selective proteolysis by gamma-secretase. These naphthyl ketones significantly
      disrupted labeling of SPP by the helical peptide probe but did not block labeling
      of SPP by the transition-state analogue probe. With respect to gamma-secretase,
      the naphthyl ketone modulators allowed labeling by the transition-state analogue
      probe but not the helical peptide probe. Thus, the naphthyl ketones appear to
      alter the docking sites of both SPP and gamma-secretase. These results indicate
      that pharmacological effects of the four different classes of inhibitors
      (transition-state analogues, helical peptides, nonsteroidal anti-inflammatory
      drugs, and naphthyl ketones) are distinct from each other, and they reveal
      similarities and differences with how they affect SPP and gamma-secretase.

PMID- 18829464
TI  - Assembly of oligomeric death domain complexes during Toll receptor signaling.
AB  - The Drosophila Toll receptor is activated by the endogenous protein ligand
      Spatzle in response to microbial stimuli in immunity and spatial cues during
      embryonic development. Downstream signaling is mediated by the adaptor proteins
      Tube, the kinase Pelle, and the Drosophila homologue of myeloid differentiation
      primary response protein (dMyD88). Here we have characterized heterodimeric
      (dMyD88-Tube) and heterotrimeric (dMyD88-Tube-Pelle) death domain complexes. We
      show that both the heterodimeric and heterotrimeric complexes form kidney-shaped
      structures and that Tube is bivalent and has separate high affinity binding sites
      for dMyD88 and Pelle. Additionally we found no interaction between the isolated
      death domains of Pelle and dMyD88. These results indicate that the mode of
      assembly of the heterotrimeric dMyD88-Tube-Pelle complex downstream of the
      activated Toll receptor is unique. The measured dissociation constants for the
      interaction between the death domains of dMyD88 and Tube and of Pelle and a
      preformed dMyD88-Tube complex are used to propose a model of the early
      postreceptor events in Drosophila Toll receptor signaling.

PMID- 18829465
TI  - Distinct specificities of Mycobacterium tuberculosis and mammalian proteasomes
      for N-acetyl tripeptide substrates.
AB  - The proteasome of Mycobacterium tuberculosis (Mtb) is a validated and drug
      treatable target for therapeutics. To lay ground-work for developing peptide
      based inhibitors with a useful degree of selectivity for the Mtb proteasome over
      those of the host, we used a library of 5,920 N-acetyl tripeptide
      aminomethylcoumarins to contrast the substrate preferences of the recombinant Mtb
      proteasome wild type and open gate mutant, the Rhodococcus erythropolis
      proteasome, and the bovine proteasome with activator PA28. The Mtb proteasome was
      distinctive in strictly preferring P1 = tryptophan, particularly in combination
      with P3 = glycine, proline, lysine or arginine. Screening results were validated
      with Michalis-Menten kinetic analyses of 21 oligopeptide aminomethyl-coumarin
      substrates. Bortezomib, a proteasome inhibitor in clinical use, and 17 analogs
      varying only at P1 were used to examine the differential impact of inhibitors on
      human and Mtb proteasomes. The results with the inhibitor panel confirmed those
      with the substrate panel in demonstrating differential preferences of Mtb and
      mammalian proteasomes at the P1 amino acid. Changing P1 in bortezomib from Leu to
      m-CF(3)-Phe led to a 220-fold increase in IC(50) against the human proteasome,
      whereas changing a P1 Ala to m-F-Phe decreased the IC(50) 400-fold against the
      Mtb proteasome. The change of a P1 Ala to m-Cl-Phe led to an 8000-fold shift in
      inhibitory potency in favor of the Mtb proteasome, resulting in 8-fold
      selectivity. Combinations of preferred amino acids at different sites may thus
      improve the species selectivity of peptide-based inhibitors that target the Mtb
      proteasome.

PMID- 18829466
TI  - Nuclear protein tyrosine phosphatase Shp-2 is one important negative regulator of
      nuclear export of telomerase reverse transcriptase.
AB  - Aging is one major risk factor for numerous diseases. The enzyme telomerase
      reverse transcriptase (TERT) plays an important role for aging and apoptosis.
      Previously, we demonstrated that inhibition of oxidative stress-induced Src
      kinase family-dependent nuclear export of TERT results in delayed replicative
      senescence and reduced apoptosis sensitivity. Therefore, the aim of this study
      was to investigate mechanisms inhibiting nuclear export of TERT. First, we
      demonstrated that H2O2-induced nuclear export of TERT was abolished in Src, Fyn,
      and Yes-deficient embryonic fibroblasts. Next, we wanted to identify one
      potential negative regulator of this export process. One candidate is the protein
      tyrosine phosphatase Shp-2 (Shp-2), which can counteract activities of the Src
      kinase family. Indeed, Shp-2 was evenly distributed between the nucleus and
      cytosol. Nuclear Shp-2 associates with TERT in endothelial cells and dissociates
      from TERT prior to its nuclear export. Overexpression of Shp-2 wt inhibited H2O2
      induced export of TERT. Overexpression of the catalytically inactive, dominant
      negative Shp-2 mutant (Shp-2(C459S)) reduced endogenous as well as overexpressed
      nuclear TERT protein and telomerase activity, whereas it had no influence on
      TERT(Y707F). Binding of TERT(Y707F) to Shp-2 is reduced compared with TERTwt.
      Ablation of Shp-2 expression led only to an increased tyrosine phosphorylation of
      TERTwt, but not of TERT(Y707F). Moreover, reduced Shp-2 expression decreased
      nuclear telomerase activity, whereas nuclear telomerase activity was increased in
      Shp-2-overexpressing endothelial cells. In conclusion, Shp-2 retains TERT in the
      nucleus by regulating tyrosine 707 phosphorylation.

PMID- 18829467
TI  - C-terminal tail of FGF19 determines its specificity toward Klotho co-receptors.
AB  - FGF19 subfamily proteins (FGF19, FGF21, and FGF23) are unique members of
      fibroblast growth factors (FGFs) that regulate energy, bile acid, glucose, lipid,
      phosphate, and vitamin D homeostasis in an endocrine fashion. Their activities
      require the presence of alpha or betaKlotho, two related single-pass
      transmembrane proteins, as co-receptors in relevant target tissues. We previously
      showed that FGF19 can bind to both alpha and betaKlotho, whereas FGF21 and FGF23
      can bind only to either betaKlotho or alphaKlotho, respectively in vitro. To
      determine the mechanism regulating the binding and specificity among FGF19
      subfamily members to Klotho family proteins, chimeric proteins between FGF19
      subfamily members or chimeric proteins between Klotho family members were
      constructed to probe the interaction between those two families. Our results
      showed that a chimera of FGF19 with the FGF21 C-terminal tail interacts only with
      betaKlotho and a chimera with the FGF23 C-terminal tail interacts only with
      alphaKlotho. FGF signaling assays also reflected the change of specificity we
      observed for the chimeras. These results identified the C-terminal tail of FGF19
      as a region necessary for its recognition of Klotho family proteins. In addition,
      chimeras between alpha and betaKlotho were also generated to probe the regions in
      Klotho proteins that are important for signaling by this FGF subfamily. Both
      FGF23 and FGF21 require intact alpha or betaKlotho for signaling, respectively,
      whereas FGF19 can signal through a Klotho chimera consisting of the N terminus of
      alphaKlotho and the C terminus of betaKlotho. Our results provide the first
      glimpse of the regions that regulate the binding specificity between this unique
      family of FGFs and their co-receptors.

PMID- 18829469
TI  - Colon cancer: it's CIN or CIMP.
AB  - Combined genetic and epigenetic analysis of sporadic colon cancer suggest that it
      can no longer be viewed as a single disease. There are at least three different
      subsets with distinct clinico-pathologic features, with important implications
      for preventions, screening, and therapy.

PMID- 18829468
TI  - Ligand-independent homomeric and heteromeric complexes between interleukin-2 or 
      9 receptor subunits and the gamma chain.
AB  - Signaling via interleukin-2 (IL-2) and interleukin-9 receptors (IL-2R and IL-9R)
      involves heteromeric interactions between specific interleukin receptor subunits,
      which bind Janus kinase 1 (JAK1) and the JAK3 binding common gamma chain (gamma
      c). The potential existence and roles of homomeric and heteromeric complexes
      before ligand binding and their modulation by ligand and JAK3 are unclear. Using
      computerized antibody-mediated immunofluorescence co-patching of epitope-tagged
      receptors at the surface of live cells, we demonstrate that IL-2Rbeta, IL
      9Ralpha, and gamma c each display a significant fraction of ligand-independent
      homomeric complexes (24-28% co-patching), whereas control co-patching levels with
      unrelated receptors are very low (7%). Heteromeric complex formation of IL2-Rbeta
      or IL-9Ralpha with gamma c is also observed in the absence of ligand (15-30%).
      Ligand binding increases this hetero-oligomerization 2-fold but does not affect
      homo-oligomerization. Co-expression of IL-2Ralpha does not affect the hetero
      oligomerization of IL-2Rbeta and gamma c. Recruitment of gamma c into
      heterocomplexes is partly at the expense of its homo-oligomerization, suggesting
      that a functional role of the latter may be to keep the receptors inactive in the
      absence of ligand. At the same time, the preformed complexes between gamma c and
      IL-2Rbeta or IL-9Ralpha promote signaling by the JAK3 A572V mutant without
      ligand, supporting a pathophysiological role for the constitutive oligomerization
      in triggering ligand-independent activation of JAK3 (and perhaps other JAK
      mutants) mutants identified in several human cancers.

PMID- 18829470
TI  - Single-agent and combination therapeutic strategies to inhibit hepatocyte growth
      factor/MET signaling in cancer.
AB  - Receptor tyrosine kinases are often aberrantly activated in human malignancies
      and contribute to cancer development and progression. Specific receptor tyrosine
      kinase inhibitors have been shown to be clinically effective therapies in subsets
      of cancer patients with either hematologic or solid tumors. Activation of the
      hepatocyte growth factor (HGF)/MET signaling pathway has been found to play a
      critical role in oncogenesis, cancer metastasis, and drug resistance. These
      observations have led to the development of agents that can effectively inhibit
      HGF/MET signaling through direct inhibition of the receptor (anti-MET
      antibodies), through inactivation of its ligand HGF (AMG102, L2G7), by
      interfering with HGF binding to MET (NK4), or by inhibiting MET kinase activity
      (PHA-665752 and SU11274). Moreover, the combination of anti-MET therapeutic
      agents with either signal transduction inhibitors (ERBB family or mTOR
      inhibitors) or with cytotoxic chemotherapy has been evaluated in preclinical
      models. These studies provide insight into the rational development of
      combination therapeutic strategies that can be evaluated in clinical trials. This
      review will discuss different strategies of MET inhibition with a specific focus
      on combination therapeutic approaches.

PMID- 18829471
TI  - Hypoxia-adenosinergic immunosuppression: tumor protection by T regulatory cells
      and cancerous tissue hypoxia.
AB  - Cancerous tissue protection from tumor-recognizing CD8(+) and CD4(+) T cells
      (antitumor T cells) limits the therapeutic potential of immunotherapies. We
      propose that tumor protection is to a large extent due to (a) inhibition of
      antitumor T cells by hypoxia-driven accumulation of extracellular adenosine in
      local tumor microenvironment and due to (b) T regulatory cell-produced
      extracellular adenosine. The adenosine triggers the immunosuppressive signaling
      via intracellular cyclic AMP-elevating A2A adenosine receptors (A2AR) on
      antitumor T cells. In addition, the activated antitumor T cells in hypoxic tumor
      microenvironment could be inhibited by elevated levels of immunosuppressive
      hypoxia-inducible factor-1alpha. Complete rejection or tumor growth retardation
      was observed when A2AR has been genetically eliminated or antagonized with
      synthetic drug or with natural A2AR antagonist 1,3,7-trimethylxanthine
      (caffeine). The promising strategy may be in combining the anti-hypoxia
      adenosinergic treatment that prevents inhibition of antitumor T cells by tumor
      produced and T regulatory cell-produced adenosine with targeting of other
      negative regulators, such as CTL antigen-4 blockade. Observations of tumor
      rejection in mice and massive prospective epidemiologic studies support the
      feasibility of anti-hypoxia-adenosinergic combined immunotherapy.

PMID- 18829472
TI  - From the editor. Bridging the gap between biostatistician and oncologist.

PMID- 18829473
TI  - Statistical issues in translational cancer research.
AB  - The explosion of knowledge about the basic biological processes and the genetics
      of cancer has led to increasing optimism that this knowledge can be put to
      practical clinical use in the near future. Indeed, important examples of
      translational approaches can already be found in the areas of drug discovery and
      development, disease diagnosis and classification, selection of therapeutic
      regimens for individual patients, and designing clinical trials. These are
      important developments but, as with any new approach, there is a danger of
      unwarranted enthusiasm and premature clinical application of laboratory results
      based on insufficient evidence. To carry out the translation of knowledge into
      practice with maximal efficiency and effectiveness, it is essential to conduct
      studies with appropriate designs and analyses based on sound statistical
      principles. This article provides an overview of some of these principles applied
      to assay development, validation of predictive models, and the design of clinical
      trials for targeted therapies.

PMID- 18829474
TI  - Statistical challenges in preprocessing in microarray experiments in cancer.
AB  - Many clinical studies incorporate genomic experiments to investigate the
      potential associations between high-dimensional molecular data and clinical
      outcome. A critical first step in the statistical analyses of these experiments
      is that the molecular data are preprocessed. This article provides an overview of
      preprocessing methods, including summary algorithms and quality control metrics
      for microarrays. Some of the ramifications and effects that preprocessing methods
      have on the statistical results are illustrated. The discussions are centered
      around a microarray experiment based on lung cancer tumor samples with survival
      as the clinical outcome of interest. The procedures that are presented focus on
      the array platform used in this study. However, many of these issues are more
      general and are applicable to other instruments for genome-wide investigation.
      The discussions here will provide insight into the statistical challenges in
      preprocessing microarrays used in clinical studies of cancer. These challenges
      should not be viewed as inconsequential nuisances but rather as important issues
      that need to be addressed so that informed conclusions can be drawn.

PMID- 18829475
TI  - Validation of analytic methods for biomarkers used in drug development.
AB  - The role of biomarkers in drug discovery and development has gained precedence
      over the years. As biomarkers become integrated into drug development and
      clinical trials, quality assurance and, in particular, assay validation become
      essential with the need to establish standardized guidelines for analytic methods
      used in biomarker measurements. New biomarkers can revolutionize both the
      development and use of therapeutics but are contingent on the establishment of a
      concrete validation process that addresses technology integration and method
      validation as well as regulatory pathways for efficient biomarker development.
      This perspective focuses on the general principles of the biomarker validation
      process with an emphasis on assay validation and the collaborative efforts
      undertaken by various sectors to promote the standardization of this procedure
      for efficient biomarker development.

PMID- 18829476
TI  - Validation of biomarker-based risk prediction models.
AB  - The increasing availability and use of predictive models to facilitate informed
      decision making highlights the need for careful assessment of the validity of
      these models. In particular, models involving biomarkers require careful
      validation for two reasons: issues with overfitting when complex models involve a
      large number of biomarkers, and interlaboratory variation in assays used to
      measure biomarkers. In this article, we distinguish between internal and external
      statistical validation. Internal validation, involving training-testing splits of
      the available data or cross-validation, is a necessary component of the model
      building process and can provide valid assessments of model performance. External
      validation consists of assessing model performance on one or more data sets
      collected by different investigators from different institutions. External
      validation is a more rigorous procedure necessary for evaluating whether the
      predictive model will generalize to populations other than the one on which it
      was developed. We stress the need for an external data set to be truly external,
      that is, to play no role in model development and ideally be completely
      unavailable to the researchers building the model. In addition to reviewing
      different types of validation, we describe different types and features of
      predictive models and strategies for model building, as well as measures
      appropriate for assessing their performance in the context of validation. No
      single measure can characterize the different components of the prediction, and
      the use of multiple summary measures is recommended.

PMID- 18829477
TI  - The use of genomics in clinical trial design.
AB  - Many cancer treatments benefit only a minority of patients who receive them. This
      results in an enormous burden on patients and on the health care system. The
      problem will become even greater with the increasing use of molecularly targeted
      agents whose benefits are likely to be more selective unless the drug development
      process is modified to include co-development of companion diagnostics. Whole
      genome biotechnology and decreasing costs of genome sequencing make it
      increasingly possible to achieve an era of predictive medicine in oncology
      therapeutics. The challenges are numerous and substantial but are not primarily
      technological. They involve organizing publicly funded diagnostics of deregulated
      pathways, adopting new paradigms for drug development, and developing incentives
      for industry to incur the complexity and expense of co-development of drugs and
      companion diagnostics. This article reviews some designs for phase III clinical
      trials that may facilitate movement to a more predictive oncology.

PMID- 18829478
TI  - Sonic hedgehog promotes desmoplasia in pancreatic cancer.
AB  - PURPOSE: We investigated the contribution of Sonic hedgehog (SHH) to pancreatic
      cancer progression. EXPERIMENTAL DESIGN: We expressed SHH in a transformed
      primary ductal-derived epithelial cell line from the human pancreas, transformed
      hTert-HPNE (T-HPNE), and evaluated the effects on tumor growth. We also directly
      inhibited the activity of SHH in vivo by administering a blocking antibody to
      mice challenged orthotopically with the Capan-2 pancreatic cancer cell line,
      which is known to express SHH and form moderately differentiated tumors in nude
      mice. RESULTS: Our data provide evidence that expression of SHH influences tumor
      growth by contributing to the formation of desmoplasia in pancreatic cancer. We
      further show that SHH affects the differentiation and motility of human
      pancreatic stellate cells and fibroblasts. CONCLUSIONS: These data suggest that
      SHH contributes to the formation of desmoplasia in pancreatic cancer, an
      important component of the tumor microenvironment.

PMID- 18829479
TI  - CpG island methylator phenotype associates with low-degree chromosomal
      abnormalities in colorectal cancer.
AB  - PURPOSE: Aberrant promoter methylation and genomic instability occur frequently
      during colorectal cancer development. CpG island methylator phenotype (CIMP) has
      been shown to associate with microsatellite instability, and BRAF mutation and is
      often found in the right-side colon. Nevertheless, the relative importance of
      CIMP and chromosomal instability (CIN) for tumorigenesis has yet to be thoroughly
      investigated in sporadic colorectal cancers. EXPERIMENTAL DESIGN: We determined
      CIMP in 161 primary colorectal cancers and 66 matched normal mucosae using a
      quantitative bisulfite/PCR/ligase detection reaction (LDR)/Universal Array assay.
      The validity of CIMP was confirmed in a subset of 60 primary tumors using
      MethyLight assay and five independent markers. In parallel, CIN was analyzed in
      the same study cohort using Affymetrix 50K Human Mapping arrays. RESULTS: The
      identified CIMP-positive cancers correlate with microsatellite instability (P =
      0.075) and the BRAF mutation V600E (P = 0.00005). The array-based high-resolution
      analysis of chromosomal aberrations indicated that the degree of aneuploidy is
      spread over a wide spectrum among analyzed colorectal cancers. Whether CIN was
      defined by copy number variations in selected microsatellite loci (criterion 1)
      or considered as a continuous variable (criterion 2), CIMP-positive samples
      showed a strong correlation with low-degree chromosomal aberrations (P = 0.075
      and P = 0.012, respectively). Similar correlations were observed when CIMP was
      determined by MethyLight assay (P = 0.001 and P = 0.013, respectively).
      CONCLUSION: CIMP-positive tumors generally possess lower chromosomal aberrations,
      which may only be revealed using a genome-wide approach. The significant
      difference in the degree of chromosomal aberrations between CIMP-positive and the
      remainder of samples suggests that epigenetic (CIMP) and genetic (CIN)
      abnormalities may arise from independent molecular mechanisms of tumor
      progression.

PMID- 18829480
TI  - Immunohistochemical expression of basic fibroblast growth factor and fibroblast
      growth factor receptors 1 and 2 in the pathogenesis of lung cancer.
AB  - PURPOSE: To identify the patterns of protein expression of basic fibroblast
      growth factor (bFGF) and FGF receptors 1 and 2 in non-small cell lung carcinoma
      (NSCLC) and their role in the early pathogenesis of squamous cell carcinoma (SCC)
      of the lung. EXPERIMENTAL DESIGN: Archived tissue from NSCLC (adenocarcinoma and
      SCC; n = 321) and adjacent bronchial epithelial specimens (n = 426) were analyzed
      for the immunohistochemical expression of bFGF, FGFR1, and FGFR2, and the
      findings were correlated with clinicopathologic features of the patients.
      RESULTS: High expression of bFGF, FGFR1, and FGFR2 was shown in most NSCLC
      tumors. The pattern of expression for all markers varied according to tumor
      histologic type and cellular localization. Cytoplasmic expression scores were
      significantly higher in tumors than in normal epithelia. Nuclear bFGF (P = 0.03)
      and FGFR1 (P = 0.02) levels were significantly higher in women than in men.
      Although cytoplasmic FGFR1 expression was significantly higher (P = 0.002) in
      ever smokers than in never smokers, nuclear FGFR1 (P = 0.0001) and FGFR2 (P =
      0.003) expression was significantly higher in never smokers. Different prognostic
      patterns for the expression of these markers were detected for both NSCLC
      histologic types. Dysplastic changes showed significantly higher expression of
      all markers compared with squamous metaplasia. CONCLUSIONS: bFGF, FGFR1, and
      FGFR2 are frequently overexpressed in SCC and adenocarcinoma of the lung. bFGF
      signaling pathway activation may be an early phenomenon in the pathogenesis of
      SCC and thus an attractive novel target for lung cancer chemopreventive and
      therapeutic strategies.

PMID- 18829481
TI  - Immunohistochemical and biogenetic features of diffuse-type tenosynovial giant
      cell tumors: the potential roles of cyclin A, P53, and deletion of 15q in
      sarcomatous transformation.
AB  - PURPOSE: Diffuse-type tenosynovial giant cell tumor (D-TSGCT) is an aggressive
      proliferation of synovial-like mononuclear cells with inflammatory infiltrates.
      Despite the COL6A3-CSF1 gene fusion discovered in benign lesions, molecular
      aberrations of malignant D-TSGCTs remain unidentified. EXPERIMENTAL DESIGN: We
      used fluorescent in situ hybridization and in situ hybridization to evaluate CSF1
      translocation and mRNA expression in six malignant D-TSGCTs, which were further
      immunohistochemically compared with 24 benign cases for cell cycle regulators
      involving G(1) phase and G(1)-S transition. Comparative genomic hybridization,
      real-time reverse transcription-PCR, and a combination of laser microdissection
      and sequencing were adopted to assess chromosomal imbalances, cyclin A
      expression, and TP53 gene, respectively. RESULTS: Five of six malignant D-TSGCTs
      displayed CSF1 mRNA expression by in situ hybridization, despite only one having
      CSF1 translocation. Cyclin A (P = 0.008) and P53 (P < 0.001) could distinguish
      malignant from benign lesions without overlaps in labeling indices. Cyclin A
      transcripts were more abundant in malignant D-TSGCTs (P < 0.001). All malignant
      cases revealed a wild-type TP53 gene, which was validated by an antibody
      specifically against wild-type P53 protein. Chromosomal imbalances were only
      detected in malignant D-TSGCTs, with DNA losses predominating over gains.
      Notably, -15q was recurrently identified in five malignant D-TSGCTs, four of
      which showed a minimal overlapping deletion at 15q22-24. CONCLUSIONS: Deregulated
      CFS1 overexpression is frequent in malignant D-TSGCTs. The sarcomatous
      transformation involves aberrations of cyclin A, P53, and chromosome arm 15q.
      Cyclin A mRNA is up-regulated in malignant D-TSGCTs. Non-random losses at 15q22
      24 suggest candidate tumor suppressor gene(s) in this region. However, P53
      overexpression is likely caused by alternative mechanisms rather than mutations
      in hotspot exons.

PMID- 18829482
TI  - Deletions of CDKN2C in multiple myeloma: biological and clinical implications.
AB  - PURPOSE: Deletions of chromosome 1 have been described in 7% to 40% of cases of
      myeloma with inconsistent clinical consequences. CDKN2C at 1p32.3 has been
      identified in myeloma cell lines as the potential target of the deletion. We
      tested the clinical impact of 1p deletion and used high-resolution techniques to
      define the role of CDKN2C in primary patient material. EXPERIMENTAL DESIGN: We
      analyzed 515 cases of monoclonal gammopathy of undetermined significance (MGUS),
      smoldering multiple myeloma (SMM), and newly diagnosed multiple myeloma using
      fluorescence in situ hybridization (FISH) for deletions of CDKN2C. In 78 myeloma
      cases, we carried out Affymetrix single nucleotide polymorphism mapping and U133
      Plus 2.0 expression arrays. In addition, we did mutation, methylation, and
      Western blotting analysis. RESULTS: By FISH we identified deletion of 1p32.3
      (CDKN2C) in 3 of 66 MGUS (4.5%), 4 of 39 SMM (10.3%), and 55 of 369 multiple
      myeloma cases (15%). We examined the impact of copy number change at CDKN2C on
      overall survival (OS), and found that the cases with either hemizygous or
      homozygous deletion of CDKN2C had a worse OS compared with cases that were intact
      at this region (22 months versus 38 months; P = 0.003). Using gene mapping we
      identified three homozygous deletions at 1p32.3, containing CDKN2C, all of which
      lacked expression of CDKN2C. Cases with homozygous deletions of CDKN2C were the
      most proliferative myelomas, defined by an expression-based proliferation index,
      consistent with its biological function as a cyclin-dependent kinase inhibitor.
      CONCLUSIONS: Our results suggest that deletions of CDKN2C are important in the
      progression and clinical outcome of myeloma.

PMID- 18829483
TI  - Constitutively activated STAT3 frequently coexpresses with epidermal growth
      factor receptor in high-grade gliomas and targeting STAT3 sensitizes them to
      Iressa and alkylators.
AB  - PURPOSE: The goals of this study are to elucidate the relationship of the
      oncogenic transcription factor signal transducer and activator of transcription 3
      (STAT3) with glioma aggressiveness and to understand the role of high STAT3
      activity in the resistance of malignant gliomas and medulloblastomas to
      chemotherapy. EXPERIMENTAL DESIGN: Immunohistochemical staining and biochemical
      methods were used to examine the extent of STAT3 activation and EGFR expression
      in primary specimens and cell lines, respectively. Cellular response to drug
      treatments was determined using cell cytotoxicity and clonogenic growth assays.
      RESULTS: We found STAT3 to be constitutively activated in 60% of primary high
      grade/malignant gliomas and the extent of activation correlated positively with
      glioma grade. High levels of activated/phosphorylated STAT3 were also present in
      cultured human malignant glioma and medulloblastoma cells. Three STAT3-activating
      kinases, Janus-activated kinase 2 (JAK2), EGFR, and EGFRvIII, contributed to
      STAT3 activation. An inhibitor to JAK2/STAT3, JSI-124, significantly reduced
      expression of STAT3 target genes, suppressed cancer cell growth, and induced
      apoptosis. Furthermore, we found that STAT3 constitutive activation coexisted
      with EGFR expression in 27.2% of primary high-grade/malignant gliomas and such
      coexpression correlated positively with glioma grade. Combination of an anti-EGFR
      agent Iressa and a JAK2/STAT3 inhibitor synergistically suppressed STAT3
      activation and potently killed glioblastoma cell lines that expressed EGFR or
      EGFRvIII. JSI-124 also sensitized malignant glioma and medulloblastoma cells to
      temozolomide, 1,3-bis(2-chloroethyl)-1-nitrosourea, and cisplatin in which a
      synergism existed between JSI-124 and cisplatin. CONCLUSION: STAT3 constitutive
      activation, alone and in concurrence with EGFR expression, plays an important
      role in high-grade/malignant gliomas and targeting STAT3/JAK2 sensitizes these
      tumors to anti-EGFR and alkylating agents.

PMID- 18829484
TI  - Androgen-regulated and highly tumorigenic human prostate cancer cell line
      established from a transplantable primary CWR22 tumor.
AB  - PURPOSE: One of the major obstacles in understanding the molecular mechanisms
      underlying the transition of prostate cancer growth from androgen dependency to a
      hormone-refractory state is the lack of androgen-regulated and tumorigenic human
      prostate cancer cell lines. EXPERIMENTAL DESIGN: We have established and
      characterized a new human prostate cancer cell line, CWR22Pc, derived from the
      primary CWR22 human prostate xenograft tumors. RESULTS: The growth of CWR22Pc
      cells is induced markedly by dihydrotestosterone, and CWR22Pc cells express high
      levels of androgen receptor (AR) and prostate-specific antigen (PSA).
      Importantly, PSA expression in CWR22Pc cells is regulated by androgens. Stat5a/b,
      Stat3, Akt, and mitogen-activated protein kinase were constitutively active or
      cytokine inducible in CWR22Pc cells. The AR in CWR22Pc cells contains the H874Y
      mutation, but not the exon 3 duplication or other mutations. When inoculated
      subcutaneously into dihydrotestosterone-supplemented castrated nude mice, large
      tumors formed rapidly in 20 of 20 mice, whereas no tumors developed in mice
      without circulating dihydrotestosterone. Moreover, the serum PSA levels
      correlated with the tumor volumes. When androgens were withdrawn from the CWR22Pc
      tumors grown in nude mice, the tumors initially shrank but regrew back as
      androgen-independent tumors. CONCLUSIONS: This androgen-regulated and tumorigenic
      human prostate cancer cell line provides a valuable tool for studies on androgen
      regulation of prostate cancer cells and on the molecular mechanisms taking place
      in growth promotion of prostate cancer when androgens are withdrawn from the
      growth environment. CWR22Pc cells also provide a model system for studies on the
      regulation of transcriptional activity of mutated H874YAR in a prostate cancer
      cell context.

PMID- 18829485
TI  - Effects of manganese superoxide dismutase silencing on androgen receptor function
      and gene regulation: implications for castration-resistant prostate cancer.
AB  - PURPOSE: Advanced prostate cancer is first treated with androgen deprivation
      therapy. However, tumors become resistant to and grow despite castrate levels of
      testosterone. Growth and proliferation of CRPC is mediated by gain-of-function
      changes in the AR and AR reactivation. Expression of manganese superoxide
      dismutase (SOD2), which regulates cellular ROS, is markedly down-regulated in
      CRPC when compared with hormone-responsive tumors. EXPERIMENTAL DESIGN: Here, we
      knocked down SOD2 expression in AR-expressing LNCaP prostate cancer cells and
      determined gene expression changes, transcription factor binding, and AR
      transcription activity in SOD2 knockdown cells. RESULTS: SOD2 knockdown results
      in an increase in ROS. Gene expression changes induced by SOD2 knockdown results
      in the up-regulation of genes that are also androgen responsive and 46% of genes
      up-regulated 2-fold by the androgen ligand R1881 are also up-regulated to the
      same extent with SOD2 knockdown. The induction of many of these genes with SOD2
      knockdown, such as VEGFA and FKBP5, is reversible with the antioxidant N
      acetylcysteine, suggesting that this mechanism is directly linked to ROS.
      Furthermore, an array for transcription factor DNA-binding activity shows that
      SOD2 knockdown induces DNA binding by several transcription factors, including
      AR. SOD2 knockdown-induced AR activation was confirmed by electrophoretic
      mobility shift assay and luciferase activity, and both were readily reversible
      with N-acetylcysteine. CONCLUSIONS: These findings show that down-regulation of
      SOD2 induces AR activity in a ROS-dependent manner, and suggest that there may be
      a role for antioxidant therapy in CRPC.

PMID- 18829486
TI  - Negative regulation of the osteoblast function in multiple myeloma through the
      repressor gene E4BP4 activated by malignant plasma cells.
AB  - PURPOSE: To explore the pathogenetic mechanisms that suppress the osteoblast
      function in multiple myeloma because osteogenesis results in defective new bone
      formation and repair. EXPERIMENTAL DESIGN: Microarray gene analysis revealed the
      overexpression of E4BP4, a transcriptional repressor gene, in normal osteoblasts
      cocultured with myeloma cells that were releasing the parathyroid hormone-related
      protein (PTHrP). Thus, the effect of E4BP4 was assessed in PTHrP-stimulated
      osteoblasts by measuring the RNA levels of both Runx2 and Osterix as major
      osteoblast transcriptional activators. Because E4BP4 is a negative regulator of
      the cyclooxygenase-2 (COX-2) pathway that drives the expression of both Runx2 and
      Osterix, these factors were investigated after prostaglandin E(2) treatment to
      overcome the COX-2 defect as well as in E4BP4-silenced osteoblasts. Finally,
      E4BP4, PTHrP, Osterix, and osteocalcin levels were measured in vivo in patients
      with bone disease together with the E4BP4 protein in bone biopsies. RESULTS:
      E4BP4 was specifically induced by PTHrP and inhibited both Runx2 and Osterix,
      whereas E4BP4-silenced osteoblasts expressed functional levels of both factors.
      The prostaglandin E(2) treatment of E4BP4-up-regulated osteoblasts promptly
      restored Runx2 and Osterix activities, suggesting that integrity of COX-2 pathway
      is essential for their transcription. Down-regulation of Osterix by E4BP4 was
      confirmed in vivo by its inverse levels in osteoblasts from myeloma patients with
      increased serum PTHrP, whose bone biopsies expressed the E4BP4 protein.
      CONCLUSIONS: Our data support the role of E4BP4 as osteoblast transcriptional
      repressor in inhibiting both Runx2 and Osterix in myeloma bone disease and
      correlate its effect with the increased PTHrP activity.

PMID- 18829487
TI  - Epidermal growth factor receptor mutations in small cell lung cancer.
AB  - PURPOSE: The vast majority of epidermal growth factor receptor (EGFR) mutations
      occur in lung adenocarcinoma, and even rare cases of other subtypes with this
      mutation, such as adenosquamous cell carcinoma, are associated with
      adenocarcinoma histology. According to this adenocarcinoma-specific nature of
      EGFR mutation, analysis of EGFR mutations with small cell lung cancers (SCLC) may
      provide a clue to its histogenesis. EXPERIMENTAL DESIGN: The mutational status of
      the EGFR gene was accessed in a cohort of 122 patients with SCLC; all patients
      were from a single institute. When the EGFR mutated, its gene copy number was
      also examined. RESULTS: EGFR mutations were detected in five SCLCs (4%). The
      patients were mainly in the light smoker and histologic combined subtype. All but
      one of the tumors harbored gene amplifications. Notably, in three tumors of the
      combined SCLC subtype, both components of adenocarcinoma and SCLC harbored an
      EGFR mutation, whereas gene amplification was detected only in the adenocarcinoma
      component. A partial response was achieved in a patient (with an EGFR mutation)
      who was treated with gefitinib. CONCLUSIONS: Although EGFR mutations are rare in
      SCLC, a combined subtype of SCLC with adenocarcinoma in light smokers may have a
      chance of harboring EGFR mutations. For patients with an EGFR mutation, EGFR
      tyrosine kinase inhibitor can be a treatment option. In terms of molecular
      pathogenesis, it is suggested that some SCLCs may have developed from pre
      existing adenocarcinomas with EGFR mutations, but the development may not be
      simply linear, taking into consideration the discordant distribution of EGFR
      amplification.

PMID- 18829488
TI  - IFN-induced transmembrane protein 1 promotes invasion at early stage of head and
      neck cancer progression.
AB  - PURPOSE: Head and neck squamous cell carcinoma (HNSCC) shows persistent invasion
      that frequently leads to local recurrence and distant lymphatic metastasis.
      However, molecular mechanisms associated with invasion of HNSCC remain poorly
      understood. We identified IFN-induced transmembrane protein 1 (IFITM1) as a
      candidate gene for promoting the invasion of HNSCC by comparing the gene
      expression profiles between parent and a highly invasive clone. Therefore, we
      examined the role of IFITM1 in the invasion of HNSCC. EXPERIMENTAL DESIGN: IFITM1
      expression was examined in HNSCC cell lines and cases by reverse transcription
      PCR and immunohistochemistry. IFITM1 overexpressing and knockdown cells were
      generated, and the invasiveness of these cells was examined by in vitro invasion
      assay. Gene expression profiling of HNSCC cells overexpressing IFITM1 versus
      control cells was examined by microarray. RESULTS: HNSCC cells expressed IFITM1
      mRNA at higher levels, whereas normal cells did not. By immunohistochemistry,
      IFITM1 expression was observed in early invasive HNSCC and invasive HNSCC.
      Interestingly, IFITM1 was expressed at the invasive front of early invasive
      HNSCC, and higher expression of IFITM1 was found in invasive HNSCC. In fact,
      IFITM1 overexpression promoted and IFITM1 knockdown suppressed the invasion of
      HNSCC cells in vitro. Gene expression profiling of HNSCC cells overexpressing
      IFITM1 versus control cells revealed that several genes, including matrix
      metalloproteinase, were up-regulated in IFITM1 overexpressing cells. CONCLUSION:
      Our findings suggest that IFITM1 plays an important role for the invasion at the
      early stage of HNSCC progression and that IFITM1 can be a therapeutic target for
      HNSCC.

PMID- 18829489
TI  - Cotreatment with vorinostat enhances activity of MK-0457 (VX-680) against acute
      and chronic myelogenous leukemia cells.
AB  - PURPOSE: We determined the effects of vorinostat (suberoylanalide hydroxamic
      acid) and/or MK-0457 (VX-680), an Aurora kinase inhibitor on the cultured human
      (HL-60, OCI-AML3, and K562) and primary acute myelogenous leukemia (AML) and
      chronic myelogenous leukemia (CML), as well as on the murine pro-B BaF3 cells
      with ectopic expression of the unmutated and mutant forms of Bcr-Abl.
      EXPERIMENTAL DESIGN: Following exposure to MK-0457 and/or vorinostat, apoptosis,
      loss of viability, as well as activity and levels of Aurora kinase and Bcr-Abl
      proteins were determined. RESULTS: Treatment with MK-0457 decreased the
      phosphorylation of Aurora kinase substrates including serine (S)10 on histone H3
      and survivin, and led to aberrant mitosis, DNA endoreduplication as well as
      apoptosis of the cultured human acute leukemia HL-60, OCI-AML3, and K562 cells.
      Combined treatment with vorinostat and MK-0457 resulted in greater attenuation of
      Aurora and Bcr-Abl (in K562) kinase activity and levels as well as
      synergistically induced apoptosis of OCI-AML3, HL-60, and K562 cells. MK-0457
      plus vorinostat also induced synergistic apoptosis of BaF3 cells with ectopic
      overexpression of wild-type or mutant Bcr-Abl. Finally, cotreatment with MK-0457
      and vorinostat induced more loss of viability of primary AML and imatinib
      refractory CML than treatment with either agent alone, but exhibited minimal
      toxicity to normal CD34+ progenitor cells. CONCLUSIONS: Combined in vitro
      treatment with MK-0457 and vorinostat is highly active against cultured and
      primary leukemia cells. These findings merit in vivo testing of the combination
      against human AML and CML cells, especially against imatinib mesylate-resistant
      Bcr-AblT315I-expressing CML Cells.

PMID- 18829490
TI  - An immunotolerant HER-2/neu transgenic mouse model of metastatic breast cancer.
AB  - PURPOSE: Animal models of breast cancer metastases that recapitulate the pattern
      of metastatic progression seen in patients are lacking; metastatic breast cancer
      models do not currently exist for evaluation of immune-mediated therapies. We
      have developed and characterized a preclinical model for the evaluation of immune
      mediated metastatic breast cancer therapies. EXPERIMENTAL DESIGN: The NT2.5
      mammary tumor cell line was injected into the left cardiac ventricle of
      immunotolerant transgenic neu-N mice and athymic nu/nu mice. Metastatic
      progression was monitored by bioluminescent, small-animal magnetic resonance
      imaging, positron emission tomography, single-photon emission computed
      tomography/computed tomography imaging, and also by histopathology. Antigen
      expression in normal organs and tumor metastases was evaluated by Western blot
      analysis and flow cytometry. RESULTS: Left cardiac ventricle injection of NT2.5
      cells yielded widespread metastases in bones, liver, and spleen. Three to four
      weeks after injection, mice exhibited hind limb paralysis and occasional
      abdominal enlargement. Bioluminescence imaging of metastatic progression was
      successful in nude mice but the bioluminescent cells were rejected in
      immunocompetent mice. Other imaging modalities allowed successful imaging of
      nonbioluminescent cells. Small-animal positron emission tomography imaging
      allowed visualization of disease, in vivo, in the bones and liver. Magnetic
      resonance imaging revealed initial dissemination of the tumor cells to the bone
      marrow. Small-animal single-photon emission computed tomography/computed
      tomography imaging identified metastatic bone lesions targeted by a radiolabeled
      antibody. CONCLUSION: The model closely recapitulates the pattern of metastatic
      spread in breast cancer. This immunotolerant metastatic model is a novel addition
      to existing breast cancer models and coupling the model with in vivo imaging
      greatly facilitates the evaluation of targeted immunotherapies of metastasis.

PMID- 18829491
TI  - Dissociation of its opposing immunologic effects is critical for the optimization
      of antitumor CD8+ T-cell responses induced by interleukin 21.
AB  - PURPOSE: Interleukin 21 (IL-21) is a promising new cytokine, which is undergoing
      clinical testing as an anticancer agent. Although IL-21 provides potent
      stimulation of CD8(+) T cells, it has also been suggested that IL-21 is
      immunosuppressive by counteracting the maturation of dendritic cells. The
      dissociation of these two opposing effects may enhance the utility of IL-21 as an
      immunotherapeutic. In this study, we used a cell-based artificial antigen
      presenting cell (aAPC) lacking a functional IL-21 receptor (IL-21R) to
      investigate the immunostimulatory properties of IL-21. EXPERIMENTAL DESIGN: The
      immunosuppressive activity of IL-21 was studied using human IL-21R(+) dendritic
      cells. Antigen-specific CD8(+) T cells stimulated with human cell-based IL-21R(
      )aAPC were used to isolate the T-cell immunostimulatory effects of IL-21. The
      functional outcomes, including phenotype, cytokine production, proliferation, and
      cytotoxicity were evaluated. RESULTS: IL-21 limits the immune response by
      maintaining immunologically immature dendritic cells. However, stimulation of
      CD8(+) T cells with IL-21R(-) aAPC, which secrete IL-21, results in significant
      expansion. Although priming in the presence of IL-21 temporarily modulated the T
      cell phenotype, chronic stimulation abrogated these differences. Importantly,
      exposure to IL-21 during restimulation promoted the enrichment and expansion of
      antigen-specific CD8(+) T cells that maintained IL-2 secretion and gained
      enhanced IFN-gamma secretion. Tumor antigen-specific CTL generated in the
      presence of IL-21 recognized tumor cells efficiently, demonstrating potent
      effector functions. CONCLUSIONS: IL-21 induces opposing effects on antigen
      presenting cells and CD8(+) T cells. Strategic application of IL-21 is required
      to induce optimal clinical effects and may enable the generation of large numbers
      of highly avid tumor-specific CTL for adoptive immunotherapy.

PMID- 18829492
TI  - Multimodality imaging of IL-18--binding protein-Fc therapy of experimental lung
      metastasis.
AB  - PURPOSE: Interleukin (IL)-18 plays important roles in cancer progression and
      metastasis. The goal of this study is to identify cell lines that are most
      sensitive to stand alone IL-18-binding protein (IL-18bp)-Fc treatment, to study
      the pharmacokinetics and tumor targeting efficiency of IL-18bp-Fc, and to
      evaluate the efficacy of IL-18bp-Fc in treating breast cancer experimental lung
      metastasis by multimodality imaging. EXPERIMENTAL DESIGN: Reverse transcription
      PCR, ELISA, and other cell-based assays were done on murine 4T1, CT-26, and
      B16F10 cells. The most IL-18bp-Fc-sensitive 4T1 cells were stably transfected
      with firefly luciferase (fLuc) and injected i.v. into female BALB/C mice to
      establish the experimental lung metastasis model. Tumor targeting efficiency and
      pharmacokinetics of IL-18bp-Fc was assessed by (64)Cu-DOTA-IL-18bp-Fc positron
      emission tomography (PET) and biodistribution studies. Two groups of fLuc-4T1
      experimental lung metastasis tumor-bearing mice were each given saline or IL-18bp
      Fc (1 mg/kg) daily i.p. Bioluminescence imaging, (18)F-FDG PET, and computed
      tomography scans were done to evaluate the treatment efficacy. Ex vivo
      experiments were also carried out to validate the imaging results. RESULTS: IL
      18bp-Fc had high and specific accumulation in the fLuc-4T1 lung metastasis tumor
      as evidenced by both PET and biodistribution studies. Bioluminescence imaging,
      (18)F-FDG PET, and computed tomography scans all revealed that IL-18bp-Fc
      treatment was effective in inhibiting the lung metastasis tumor progression,
      validated by ex vivo examination of the lung. CONCLUSIONS: IL-18bp-Fc therapy can
      inhibit 4T1 breast cancer experimental lung metastasis. Noninvasive multimodality
      molecular imaging is a powerful tool for evaluating the tumor targeting
      efficiency/pharmacokinetics of the drug and effective monitoring of the
      therapeutic response.

PMID- 18829493
TI  - Brivanib alaninate, a dual inhibitor of vascular endothelial growth factor
      receptor and fibroblast growth factor receptor tyrosine kinases, induces growth
      inhibition in mouse models of human hepatocellular carcinoma.
AB  - PURPOSE: Hepatocellular carcinoma (HCC) is the fifth most common primary
      neoplasm; surgery is the only curative option but 5-year survival rates are only
      25% to 50%. Vascular endothelial growth factor (VEGF) and fibroblast growth
      factor (FGF) are known to be involved in growth and neovascularization of HCC.
      Therefore, agents that target these pathways may be effective in the treatment of
      HCC. The aim of this study was to determine the antineoplastic activity of
      brivanib alaninate, a dual inhibitor of VEGF receptor (VEGFR) and FGF receptor
      (FGFR) signaling pathways. EXPERIMENTAL DESIGN: Six different s.c. patient
      derived HCC xenografts were implanted into mice. Tumor growth was evaluated in
      mice treated with brivanib compared with control. The effects of brivanib on
      apoptosis and cell proliferation were evaluated by immunohistochemistry. The SK
      HEP1 and HepG2 cells were used to investigate the effects of brivanib on the
      VEGFR-2 and FGFR-1 signaling pathways in vitro. Western blotting was used to
      determine changes in proteins in these xenografts and cell lines. RESULTS:
      Brivanib significantly suppressed tumor growth in five of six xenograft lines.
      Furthermore, brivanib-induced growth inhibition was associated with a decrease in
      phosphorylated VEGFR-2 at Tyr(1054/1059), increased apoptosis, reduced
      microvessel density, inhibition of cell proliferation, and down-regulation of
      cell cycle regulators. The levels of FGFR-1 and FGFR-2 expression in these
      xenograft lines were positively correlated with its sensitivity to brivanib
      induced growth inhibition. In VEGF-stimulated and basic FGF stimulated SK-HEP1
      cells, brivanib significantly inhibited VEGFR-2, FGFR-1, extracellular signal
      regulated kinase 1/2, and Akt phosphorylation. CONCLUSION: This study provides a
      strong rationale for clinical investigation of brivanib in patients with HCC.

PMID- 18829494
TI  - Therapy of advanced B-lymphoma xenografts with a combination of 90Y-anti-CD22 IgG
      (epratuzumab) and unlabeled anti-CD20 IgG (veltuzumab).
AB  - PURPOSE: Antibodies are effective therapeutic agents in cancer, but cures are
      rarely if ever obtained. Combination therapies are likely to be more effective
      than a single agent. In this study, the combination of a new unconjugated
      humanized anti-CD20 IgG, veltuzumab, with a (90)Y-conjugated humanized antibody
      to CD22 (epratuzumab) was evaluated for the treatment of B-cell lymphoma in a
      nude mouse model system. EXPERIMENTAL DESIGN: Nude mice were grafted with the
      Ramos human B-lymphoma and treatment initiated when tumors were >0.1 cm(3). In
      most experiments, mice were injected first with unconjugated anti-CD20, then with
      (90)Y-anti-CD22 1 day later. Additional weekly injections of the unconjugated
      veltuzumab were administered for 3 weeks. Controls included a single agent only
      and a nonreactive control radiolabeled antibody. RESULTS: Unconjugated anti-CD20
      veltuzumab alone did not have a significant therapeutic effect, even at a total
      dose of 2.5 mg per mouse. The (90)Y-anti-CD22 epratuzumab alone induced marked
      regressions of all tumors, but they regrew in a few weeks. The combination of
      these agents cured approximately 80% of the mice. A nonreactive control antibody
      labeled with (90)Y, used without veltuzumab, had no therapeutic effect. The
      therapeutic effect of (90)Y-epratuzumab required the maximum tolerated dose of
      radioactivity, which was 160 muCi per mouse. CONCLUSIONS: These studies
      illustrate how combinations of unconjugated and radioconjugated antibodies
      against different B-cell markers can improve therapeutic outcome, and offer a new
      therapeutic paradigm for the treatment of B-cell lymphomas.

PMID- 18829496
TI  - Characteristics of dasatinib- and imatinib-resistant chronic myelogenous leukemia
      cells.
AB  - PURPOSE: Although dual src-family kinase/BCR/ABL inhibitor, dasatinib (BMS
      354825), provides therapeutic advantages to imatinib-resistant cells, the
      mechanism of dasatinib resistance was not fully known. EXPERIMENTAL DESIGN: We
      used TF-1 BCR/ABL cells, by introducing the BCR/ABL gene into a leukemia cell
      line, TF-1 and K562, and established dasatinib- (BMS-R) and imatinib-resistant
      (IM-R) cells. We characterized chronic myelogenous leukemia drug-resistant cells
      and examined intracellular signaling. RESULTS: The IC(50) of dasatinib was 0.75
      nmol/L (TF-1 BCR/ABL), 1 nmol/L (K562), 7.5 nmol/L (TF-1 BCR/ABL IM-R), 10 nmol/L
      (K562 IM-R), 15 micromol/L (TF-1 BCR/ABL BMS-R), and 25 micromol/L (K562 BMS-R).
      The number of BCR/ABL copies in resistant cell lines was the same as the parental
      cell line by fluorescence in situ hybridization analysis. There was no mutation
      in Abl kinase. We found that protein levels of BCR/ABL were reduced in dasatinib
      resistant cell lines. BCR/ABL protein was increased by treatment of an ubiquitin
      inhibitor. The Src kinase, Lck, as well as mitogen-activated protein kinase and
      Akt were activated, but p21(WAF), phosphatase and tensin homologue was reduced in
      K562 BMS-R cells. Removal of dasatinib from the culture medium of K562 BMS-R
      cells led to apoptosis, and activated caspase 3 and poly (ADP-ribose) polymerase.
      CONCLUSION: These results suggest that the expression and protein activation
      signatures identified in this study provide insight into the mechanism of
      resistance to dasatinib and imatinib and may be of therapeutic chronic
      myelogenous leukemia value clinically.

PMID- 18829495
TI  - Therapeutic IMC-C225 antibody inhibits breast cancer cell invasiveness via Vav2
      dependent activation of RhoA GTPase.
AB  - PURPOSE: Abnormalities in the expression and signaling pathways downstream of
      epidermal growth factor receptor (EGFR) contribute to progression, invasion, and
      maintenance of the malignant phenotype in human cancers. Accordingly, biological
      agents, such as the EGFR-blocking antibody IMC-C225 have promising anticancer
      potential and are currently in various stages of clinical development. Because
      use of IMC-C225 is limited, at present, only for treatment of cancer with high
      EGFR expression, the goal of the present study was to determine the effect of IMC
      C225 on the invasiveness of breast cancer cells with high and low levels of EGFR
      expression. EXPERIMENTAL DESIGN: The effect of IMC-C225 on invasion was studied
      using breast cancer cell lines with high and low levels of EGFR expression.
      RESULTS: The addition of EGF led to progressive stress fiber dissolution. In
      contrast, cells treated with IMC-C225 showed reduced invasiveness and increased
      stress-fiber formation. Interestingly, IMC-C225 pretreatment was accompanied by
      EGFR phosphorylation, as detected using an anti-phosphorylated tyrosine antibody
      (PY99), which correlated with phosphorylation of Vav2 guanine nucleotide exchange
      factor and activation of RhoA GTPase irrespective of EGFR level, and Vav2
      interacted with EGFR only in IMC-C225-treated cells. The underlying mechanism
      involved an enhanced interaction between beta1 integrins and EGFR upon IMC-C225
      treatment. CONCLUSION: Here, we defined a new mechanism for IMC-C225 that cross
      links integrins with EGFR, leading to activation of RhoA and inhibition of breast
      cancer cell invasion irrespective of the level of EGFR in the cells, thus
      providing a rationale for using IMC-C225 in the metastatic setting independent of
      the levels of EGFR.

PMID- 18829497
TI  - Therapeutic potential of replication-selective oncolytic adenoviruses on cells
      from familial and sporadic desmoid tumors.
AB  - PURPOSE: Constitutive activation of the Wnt signaling pathway is a hallmark of
      many cancers and has been associated with familial and sporadic desmoid tumors.
      The aim of the present study is to assess the therapeutic potential of oncolytic
      adenoviruses selectively replicating in cells in which the Wnt signaling pathway
      is active on primary cells from desmoid tumors. EXPERIMENTAL DESIGN: Primary
      cells extracted from familial (n = 3) or sporadic (n = 3) desmoid tumors were
      cultured short term. Cancer cell survival and viral replication were measured in
      vitro upon infection with two different oncolytic adenoviruses targeting a
      constitutive activation of the Wnt signaling pathway. Adenoviral infectivity was
      also assessed. RESULTS: Although cells extracted from one sporadic desmoid tumor
      responded very well to the oncolytic action of the adenoviruses (<20% of viable
      cells upon infection at a multiplicity of infection of 10), cells from two tumor
      samples were totally resistant to the viral action. Cells from the remaining
      samples showed intermediate sensitivity to the oncolytic viruses. These effects
      were correlated to the level of infectivity of the cells. Finally, in responder
      cells, evidences of viral replication was observed. CONCLUSIONS: Our experimental
      data suggest that the response of desmoid tumor cells to oncolytic adenovirus is
      neither correlated to the type of mutation activating the Wnt signaling pathway
      nor to the familial or sporadic nature of the tumor. In addition, they highlight
      the variability of infectivity of individual tumors and predict a great
      variability in the response to oncolytic adenoviruses.

PMID- 18829498
TI  - Integrin agonists as adjuvants in chemotherapy for melanoma.
AB  - PURPOSE: Metastatic melanomas are generally resistant to chemotherapy and
      radiation, even when wild-type for p53. These tumors often grow in small nests
      where many of the cells have little contact with extracellular matrix (ECM).
      Previous work showed that M21 melanomas undergo apoptosis in response to
      chemotherapy when cells are adherent to ECM but not in suspension. Thus, reduced
      integrin-dependent adhesion to ECM could mediate therapy resistance. The goal of
      this study was to test whether stimulation of integrin signaling could increase
      chemotherapeutic efficacy. EXPERIMENTAL DESIGN: Colony forming assays and
      survival assays were used to test the responses of melanoma lines in vitro.
      Severe combined immunodeficient mice with subcutaneous human melanomas received
      chemotherapy with or without reagents that stimulate integrin signaling; tumor
      volume was then monitored over time. RESULTS: Clonal growth assays confirmed that
      M21 cells showed reduced sensitivity to the chemotherapeutic drug 1-beta-D
      arabinofuranosylcytosine (araC). When five additional primary melanoma lines were
      screened, 80% showed higher sensitivity when adherent compared with suspended.
      Subcutaneous M21 tumors in vivo showed minimal ECM between tumor cells. To
      evaluate the importance of integrin signaling in chemoresistance in this model,
      mice were treated with araC, with or without the multivalent snake venom
      disintegrin contortrostatin or the activating anti-beta1 integrin antibody
      TS2/16. Although araC, TS2/16, or contortrostatin alone had little effect on M21
      tumor growth, combining araC with either integrin signaling reagents strongly
      reduced growth (P = 0001). CONCLUSIONS: Loss of integrin-mediated adhesion is
      rate limiting for therapeutic response in this model. Combining chemotherapy with
      reagents that stimulate integrin signaling may therefore provide a new approach
      to therapy.

PMID- 18829499
TI  - BKM1740, an acyl-tyrosine bisphosphonate amide derivative, inhibits the bone
      metastatic growth of human prostate cancer cells by inducing apoptosis.
AB  - PURPOSE: Survivin overexpression has been associated with an unfavorable outcome
      in human PCa; however, its role in metastasis remains elusive. We aim to (a)
      evaluate the clinical implications of survivin expression in PCa bone metastasis;
      (b) determine in vivo efficacy of BKM1740, a small-molecule compound, against PCa
      skeletal growth and survival; and (c) investigate molecular mechanism by which
      BKM1740 augments apoptosis in bone metastatic PCa cells. EXPERIMENTAL DESIGN:
      Survivin expression was analyzed in PCa specimens and experimental models. Bone
      metastatic C4-2 and ARCaP(M) cell lines were used to evaluate the in vitro
      effects of BKM1740 and molecular mechanism for the induction of apoptosis. C4-2
      cells were grown intratibially in athymic nude mice to evaluate the in vivo
      efficacy of BKM1740. Tumor growth in mouse bone was assessed by serum prostate
      specific antigen and radiography and confirmed by immunohistochemical analyses.
      RESULTS: Survivin expression is positively associated with clinical PCa bone
      metastasis. BKM1740 induced apoptosis in PCa cells by repressing survivin. Mice
      with established C4-2 tumors in tibia showed a marked decrease in serum prostate
      specific antigen and much improved bone architecture radiographically after
      treatment with BKM1740. Immunohistochemical assays of mouse tumor samples
      confirmed that the in vivo effects were mediated by inhibition of survivin and
      induction of apoptosis. CONCLUSIONS: Survivin expression is associated with PCa
      bone metastasis. BKM1740 treatment specifically inhibited survivin and induced
      apoptosis in vitro and was efficacious in retarding PCa skeletal growth in a
      mouse model. BKM1740 is a promising small-molecule compound that could be used to
      treat PCa bone metastasis.

PMID- 18829500
TI  - Differentiation of human embryonic stem cells into immunostimulatory dendritic
      cells under feeder-free culture conditions.
AB  - PURPOSE: The objective of this study was to develop a scalable and broadly
      applicable active immunotherapy approach against cancer, circumventing the
      limitations typically encountered with autologous vaccination strategies. We
      hypothesized that human embryonic stem cells (hESC) can serve as a virtually
      unlimited source for generating dendritic cells (DC) with potent antigen
      presenting function. Here, we investigated the developmental processes and
      requirements for generating large numbers of mature, antigen-presenting DC from
      pluripotent hESC. EXPERIMENTAL DESIGN: A feeder cell-free culture system was
      developed to differentiate hESC into mature DC sequentially through hematopoietic
      and myeloid precursor stages. RESULTS: Using this method, we were able to yield
      large numbers of mature immunostimulatory DC from hESC to enable clinical
      investigation. Upon activation, the hESC-derived DC secreted interleukin-12p70,
      migrated in response to MIP-3beta, and exhibited allostimulatory capacity. Most
      importantly, antigen-loaded, hESC-derived DC were capable of stimulating potent
      antigen-specific CD8(+) T-cell responses in an HLA class I-matched semiallogeneic
      assay system. Moreover, HLA class II-mismatched hESC-derived DC induced a potent
      Th1-type cytokine response without expanding FOXP3(+) regulatory T cells in
      vitro. CONCLUSIONS: These data suggest the development of a novel active
      immunotherapy platform to stimulate potent T-cell immunity in patients with
      intractable diseases, such as cancer or viral infection.

PMID- 18829501
TI  - N-(2,6-dimethoxypyridine-3-yl)-9-methylcarbazole-3-sulfonamide as a novel tubulin
      ligand against human cancer.
AB  - PURPOSE: We have synthesized a new tubulin ligand N-(2,6-dimethoxypyridine-3-yl)
      9-methylcarbazole-3-sulfonamide (IG-105). This work investigates its anticancer
      effect and mechanism. EXPERIMENTAL DESIGN: Anticancer efficacy was evaluated at
      the molecular target, cancer cells and nude mice. The mechanism was explored at
      submolecular, molecular, and cellular levels. RESULTS: IG-105 showed a potent
      activity against human leukemia and solid tumors in breast, liver, prostate,
      lung, skin, colon, and pancreas with IC(50) values between 0.012 and 0.298
      mumol/L. It was also active in drug-resistant tumor cells and not a P
      glycoprotein substrate. It inhibited microtubule assembly followed by M-phase
      arrest, Bcl-2 inactivation, and then apoptosis through caspase pathways. The
      colchicine pocket on tubulin is the binding site of IG-105. Nude mice experiments
      showed that IG-105 monotherapy at 100 mg/kg i.p. (q2d) yielded 81% inhibition of
      Bel-7402 hepatoma growth and at 275 mg/kg i.p. (q2d) completely inhibited the
      tumor growth. MCF-7 breast cancer in nude mice showed a similar therapeutic
      response to IG-105. Acute toxicity of IG-105 was not found even at 1,000 mg/kg
      i.p. In combination with oxaliplatin or doxorubicin, IG-105 converted each of
      these subcurative compounds into a curative treatment with complete inhibition
      for tumor growth in the hepatoma-bearing nude mice. The combination was more
      active than either drug. In no experiment was toxicity increased by combination
      chemotherapy. CONCLUSIONS: IG-105 inhibits microtubule assembly by binding at
      colchicine pocket. It shows a potent anticancer activity in vitro and in vivo and
      has good safety in mice. We consider IG-105 merits further investigation.

PMID- 18829502
TI  - Liposome-encapsulated curcumin suppresses growth of head and neck squamous cell
      carcinoma in vitro and in xenografts through the inhibition of nuclear factor
      kappaB by an AKT-independent pathway.
AB  - PURPOSE: The purpose of this study was to determine whether a liposomal
      formulation of curcumin would suppress the growth of head and neck squamous cell
      carcinoma (HNSCC) cell lines CAL27 and UM-SCC1 in vitro and in vivo. EXPERIMENTAL
      DESIGN: HNSCC cell lines were treated with liposomal curcumin at different doses
      and assayed for in vitro growth suppression using the 3-(4,5-dimethylthiazol-2
      yl)-2,5-diphenyltetrazolium bromide assay. A reporter gene assay was done on cell
      lines to study the effect of liposomal curcumin on nuclear factor kappaB
      (NFkappaB) activation. Western blot analysis was done to determine the effect of
      curcumin on the expression of NFkappaB, phospho-IkappaBalpha, phospho-AKT (pAKT),
      phospho-S6 kinase, cyclin D1, cyclooxygenase-2, matrix metalloproteinase-9, Bcl
      2, Bcl-xL, Mcl-1L, and Mcl-1S. Xenograft mouse tumors were grown and treated with
      intravenous liposomal curcumin. After 5 weeks, tumors were harvested and weighed.
      Immunohistochemistry and Western blot analyses were used to study the effect of
      liposomal curcumin on the expression of NFkappaB and pAKT. RESULTS: The addition
      of liposomal curcumin resulted in a dose-dependent growth suppression of both
      cell lines. Liposomal curcumin treatment suppressed the activation of NFkappaB
      without affecting the expression of pAKT or its downstream target phospho-S6
      kinase. Expression of cyclin D1, cyclooxygenase-2, matrix metalloproteinase-9,
      Bcl-2, Bcl-xL, Mcl-1L, and Mcl-1S were reduced, indicating the effect of curcumin
      on the NFkappaB pathway. Nude mice xenograft tumors were suppressed after 3.5
      weeks of treatment with i.v. liposomal curcumin, and there was no demonstrable
      toxicity of liposomal curcumin upon autopsy. Immunohistochemistry and Western
      blot analysis on xenograft tumors showed the inhibition of NFkappaB without
      affecting the expression of pAKT. CONCLUSIONS: Liposomal curcumin suppresses
      HNSCC growth in vitro and in vivo. The results suggest that liposomal curcumin is
      a viable nontoxic therapeutic agent for HNSCC that may work via an AKT
      independent pathway.

PMID- 18829503
TI  - Identification of GRP75 as an independent favorable prognostic marker of
      neuroblastoma by a proteomics analysis.
AB  - PURPOSE: Neuroblastoma (NB) is a heterogeneous neoplasm. Detailed biological
      discrimination is critical for the effective treatment of this disease. Because
      the tumor behavior of NB is closely associated with the histologic state of
      differentiation, we thus aimed to identify novel differentiation-associated
      markers of NB with prognostic implication. EXPERIMENTAL DESIGN: A human NB cell
      line SH-SY5Y was used as a model system to explore potential biomarkers for the
      differentiation of NB by proteomic analyses. Seventy-two NB tumor tissues were
      subsequently investigated by immunohistochemistry to validate the correlations
      between the expression of a novel prognostic marker, various clinicopathologic
      and biological factors, and patient survival. RESULTS: Using two-dimensional
      differential gel electrophoresis, we found a total of 24 spots of proteins in SH
      SY5Y cells whose expression was enhanced following differentiation. Glucose
      regulated protein 75 (GRP75) was unambiguously identified as one of the five
      proteins that were dramatically up-regulated following differentiation.
      Immunohistochemical analyses of 72 NB tumor tissues further revealed that
      positive GRP75 immunostaining is strongly correlated with differentiated
      histologies (P < 0.001), mass-screened tumors (P = 0.016), and early clinical
      stages (P < 0.001) but inversely correlated with MYCN amplification (P = 0.010).
      Univariate and multivariate survival analyses showed that GRP75 expression is an
      independent favorable prognostic factor. CONCLUSIONS: The present findings
      clearly showed that our proteomics-based novel experimental paradigm could be a
      powerful tool to uncover novel biomarkers associated with the differentiation of
      NB. Our data also substantiate an essential role of GRP75 in the differentiation
      of NB.

PMID- 18829504
TI  - Salivary proteomics for oral cancer biomarker discovery.
AB  - PURPOSE: This study aims to explore the presence of informative protein
      biomarkers in the human saliva proteome and to evaluate their potential for
      detection of oral squamous cell carcinoma (OSCC). EXPERIMENTAL DESIGN: Whole
      saliva samples were collected from patients (n = 64) with OSCC and matched
      healthy subjects (n = 64). The proteins in pooled whole saliva samples of
      patients with OSCC (n = 16) and matched healthy subjects (n = 16) were profiled
      using shotgun proteomics based on C4 reversed-phase liquid chromatography for
      prefractionation, capillary reversed-phase liquid chromatography with quadruple
      time-of-flight mass spectrometry, and Mascot sequence database searching.
      Immunoassays were used for validation of the candidate biomarkers on a new group
      of OSCC (n = 48) and matched healthy subjects (n = 48). Receiver operating
      characteristic analysis was exploited to evaluate the diagnostic value of
      discovered candidate biomarkers for OSCC. RESULTS: Subtractive proteomics
      revealed several salivary proteins at differential levels between the OSCC
      patients and matched control subjects. Five candidate biomarkers were
      successfully validated using immunoassays on an independent set of OSCC patients
      and matched healthy subjects. The combination of these candidate biomarkers
      yielded a receiver operating characteristic value of 93%, sensitivity of 90%, and
      specificity of 83% in detecting OSCC. CONCLUSION: Patient-based saliva proteomics
      is a promising approach to searching for OSCC biomarkers. The discovery of these
      new targets may lead to a simple clinical tool for the noninvasive diagnosis of
      oral cancer. Long-term longitudinal studies with large populations of individuals
      with oral cancer and those who are at high risk of developing oral cancer are
      needed to validate these potential biomarkers.

PMID- 18829506
TI  - Transesophageal endoscopic ultrasound with fine needle aspiration in the
      preoperative staging of malignant pleural mesothelioma.
AB  - PURPOSE: Surgical resection as part of a multimodality approach in malignant
      pleural mesothelioma (MPM) has a high morbidity and mortality. Because
      mediastinal lymph node (MLN) metastases are a negative prognostic factor,
      preoperative staging is of paramount importance. Transesophageal endoscopic
      ultrasound with real-time guided fine needle aspiration (EUS-FNA) enables
      accurate MLN staging in lung cancer. EXPERIMENTAL DESIGN: The feasibility and
      yield of EUS-FNA in MLN staging were prospectively analyzed in patients with
      presumed early-stage MPM considered for multimodality therapy. MLN reference
      pathology was defined by either pathologic staging or the formal demonstration of
      malignant cells by either EUS-FNA or mediastinoscopy. RESULTS: Thirty-two
      consecutive patients (81% males; median age, 61 years) with proven MPM underwent
      EUS-FNA. In 11 (34%) patients, a negative EUS-FNA or mediastinoscopy was not
      confirmed by surgical MLN dissection because of clinical deterioration or disease
      progression. In 21 (66%) patients, a formal pathology of the MLN was obtained and
      staging with EUS-FNA was positive in 4 (19%). Mediastinoscopy did not result in a
      greater yield of MLN metastasis as compared with EUS-FNA. Thoracotomy with
      complete lymph node dissection was done in 17 (81%). The overall prevalence of
      MLN metastasis was 24%, and the sensitivity of EUS-FNA was 80% (95% confidence
      interval, 28-99%) with a specificity of 100% (95% confidence interval, 79-100%).
      One patient had esophageal perforation related to EUS-FNA. CONCLUSIONS: EUS-FNA
      is feasible and sensitive for MLN staging in patients with MPM who are candidate
      for multimodality treatment. These data warrant further evaluation.

PMID- 18829505
TI  - Shedding of distinct cryptic collagen epitope (HU177) in sera of melanoma
      patients.
AB  - PURPOSE: Extracellular matrix remodeling during tumor growth plays an important
      role in angiogenesis. Our preclinical data suggest that a newly identified
      cryptic epitope (HU177) within collagen type IV regulates endothelial and
      melanoma cell adhesion in vitro and angiogenesis in vivo. In this study, we
      investigated the clinical relevance of HUI77 shedding in melanoma patient sera.
      EXPERIMENTAL DESIGN: Serum samples from 291 melanoma patients prospectively
      enrolled at the New York University Medical Center and 106 control subjects were
      analyzed for HU177 epitope concentration by a newly developed sandwich ELISA
      assay. HU177 serum levels were then correlated with clinical and pathologic
      parameters. RESULTS: Mean HU177 epitope concentration was 5.8 ng/mL (range, 0
      139.8 ng/mL). A significant correlation was observed between HU177 concentration
      and nodular melanoma histologic subtype [nodular, 10.3 +/- 1.6 ng/mL (mean +/-
      SE); superficial spreading melanoma, 4.5 +/- 1.1 ng/mL; all others, 6.1 +/- 2.1
      ng/mL; P = 0.01 by ANOVA test]. Increased HU177 shedding also correlated with
      tumor thickness (< or =1.00 mm, 3.8 +/- 1.1 ng/mL; 1.01-3.99 mm, 8.7 +/- 1.3
      ng/mL; > or =4.00 mm, 10.3 +/- 2.4 ng/mL; P = 0.003 by ANOVA). After multivariate
      analysis controlling for thickness, the correlation between higher HU177
      concentration and nodular subtype remained significant (P = 0.03). The mean HU177
      epitope concentration in control subjects was 2.4 ng/mL. CONCLUSIONS: We report
      that primary melanoma can induce detectable changes in systemic levels of cryptic
      epitope shedding. Our data also support that nodular melanoma might be
      biologically distinct compared with superficial spreading type melanoma. As
      targeted interventions against cryptic collagen epitopes are currently undergoing
      phase I clinical trial testing, these findings indicate that patients with
      nodular melanoma may be more susceptible to such targeted therapies.

PMID- 18829507
TI  - Reprimo as a potential biomarker for early detection in gastric cancer.
AB  - PURPOSE: Gastric cancer is a curable disease if diagnosed at early stage.
      However, most cases are diagnosed at advanced stage because of the lack of
      screening programs. Therefore, the identification of plasma biomarkers for early
      detection is necessary. EXPERIMENTAL DESIGN: To search for these biomarkers, we
      evaluated the DNA methylation patterns of 24 genes by Methylation-specific PCR in
      primary tissues from 32 retrospectively collected gastric cancer cases (testing
      group). Correlation between methylation and gene expression was evaluated in the
      MKN-45 cell line after treatment with 5-aza-2'-deoxycytidine. The most frequently
      hypermethylated genes were next evaluated in primary tissues and plasma samples
      from 43 prospectively collected gastric cancer cases as well as plasma samples
      from 31 asymptomatic age- and gender-matched controls (validation group).
      RESULTS: In the testing group, 11 genes were hypermethylated in at least 50% of
      cases (APC, SHP1, E-cadherin, ER, Reprimo, SEMA3B, 3OST2, p14, p15, DAPK, and
      p16). Eight genes (BRCA1, p73, RARbeta, hMLH1, RIZI, RUNX3, MGMT, and TIMP3) were
      statistically associated with a particular variant of gastric cancer, the signet
      ring cell type (P = 0.03). Seven genes (APC, SHP1, E-cadherin, ER, Reprimo,
      SEMA3B, and 3OST2) were next evaluated in the validation group. We confirm the
      high frequency of methylation in primary tumors for all seven genes. However,
      only APC and Reprimo were frequently methylated in pair plasma samples. In
      asymptomatic controls, only Reprimo was infrequently methylated in comparison
      with plasma from gastric cancer cases (P < 0.001). CONCLUSION: Our results
      identified specific methylation profile associated to signet-ring cell-type
      histology and aberrant hypermethylation of Reprimo as a potential biomarker for
      early detection of gastric cancer.

PMID- 18829508
TI  - A phase I-II study of docetaxel and atrasentan in men with castration-resistant
      metastatic prostate cancer.
AB  - PURPOSE: The primary aims of this phase I-II study were to determine the maximum
      tolerated dose, dose-limiting toxicity, pharmacokinetics, and preliminary
      efficacy of the combination of docetaxel and the endothelin A receptor antagonist
      atrasentan as first-line treatment for men with metastatic castration-resistant
      prostate cancer. EXPERIMENTAL DESIGN: Patients were treated with docetaxel at
      doses ranging from 60 to 75 mg/m(2) every 21 days, with daily oral atrasentan 10
      mg starting on day 3. Patients were treated until evidence of disease progression
      or unacceptable toxicity. RESULTS: Thirty-one patients were enrolled over three
      docetaxel dose levels (8 at 60 mg/m(2), 19 at 70 mg/m(2), and 4 at 75 mg/m(2))
      including dose expansion at 70 mg/m(2). The maximum tolerated dose of docetaxel
      was 70 to 75 mg/m(2). Drug-related grade 3-4 toxicities included neutropenia (50
      63%) and febrile neutropenia (16-25%); other grade 1-2 toxicities included
      fatigue, peripheral edema, diarrhea, headache, rhinitis, anorexia, and nausea.
      Confirmed prostate-specific antigen (PSA) responses were observed in 23% [95%
      confidence interval (95% CI), 10-41%]; the rate of >30% declines in PSA was 35%
      (95% CI, 19-55%). Median overall survival was 17.6 months (95% CI, 13.0-23.2) and
      median progression-free survival was 4.2 months (95% CI, 2.3-5.8). Significant
      declines in bone alkaline phosphatase and serum N-telopeptides were observed with
      therapy. CONCLUSIONS: The maximum tolerated dose of every-3-week docetaxel with
      10 mg atrasentan is 70 to 75 mg/m(2). Overall survival and progression-free
      survival are comparable to that seen with docetaxel and prednisone, whereas the
      rates of PSA decline are slightly lower than expected. A phase III study of this
      combination with prednisone has been initiated and is ongoing.

PMID- 18829509
TI  - A phase I-II study of combined blockade of the ErbB receptor network with
      trastuzumab and gefitinib in patients with HER2 (ErbB2)-overexpressing metastatic
      breast cancer.
AB  - PURPOSE: To determine the safety, and efficacy of the epidermal growth factor
      receptor tyrosine kinase inhibitor gefitinib in combination with trastuzumab in
      patients with metastatic HER2-positive metastatic breast cancer. EXPERIMENTAL
      DESIGN: Patients with HER2-overexpressing breast cancer were treated with
      trastuzumab 2 mg/kg/week and gefitinib 250 to 500 mg/day. The primary end point
      of the study was to increase the proportion progression-free from 50% to 65% at 6
      months in chemotherapy-naive patients and from 50% to 70% at 3 months in patients
      previously treated with chemotherapy in the metastatic setting. RESULTS: In the
      phase I study, all patients treated with gefitinib 500 mg/day developed grade 3
      diarrhea. The phase II study was conducted using trastuzumab and gefitinib 250
      mg/day. One patient achieved a complete response, 2 had a partial response, and 6
      had stable disease for an overall response rate of 9% and a clinical benefit rate
      of 28% (9 of 32). Median time to progression (TTP) was 3 months (95% confidence
      interval, 2.3-4.1) in patients with no prior systemic therapy in the metastatic
      setting (n = 23). In patients treated with prior systemic therapy (n = 9), the
      median TTP of 5.3 months (95% confidence interval, 2.8-8.1). Overall median
      survival was 27 months. TTP was similar in EGFR-positive compared with EGFR
      negative patients. CONCLUSIONS: Gefitinib 250 mg/day was the maximal dose that
      can be safely administered with weekly trastuzumab. Interim analysis of the
      efficacy suggested that the combination was unlikely to result in clinical
      benefit compared with trastuzumab alone. These results do not support the use of
      this combination in patients with HER2-positive breast cancer.

PMID- 18829510
TI  - Single nucleotide polymorphisms, apoptosis, and the development of severe late
      adverse effects after radiotherapy.
AB  - PURPOSE: Evidence has accumulated in recent years suggestive of a genetic basis
      for a susceptibility to the development of radiation injury after cancer
      radiotherapy. The purpose of this study was to assess whether patients with
      severe radiation-induced sequelae (RIS; i.e., National Cancer Institute/CTCv3.0
      grade, > or =3) display both a low capacity of radiation-induced CD8 lymphocyte
      apoptosis (RILA) in vitro and possess certain single nucleotide polymorphisms
      (SNP) located in candidate genes associated with the response of cells to
      radiation. EXPERIMENTAL DESIGN: DNA was isolated from blood samples obtained from
      patients (n = 399) included in the Swiss prospective study evaluating the
      predictive effect of in vitro RILA and RIS. SNPs in the ATM, SOD2, XRCC1, XRCC3,
      TGFB1, and RAD21 genes were screened in patients who experienced severe RIS
      (group A, n = 16) and control subjects who did not manifest any evidence of RIS
      (group B, n = 18). RESULTS: Overall, 13 and 21 patients were found to possess a
      total of <4 and > or =4 SNPs in the candidate genes. The median (range) RILA in
      group A was 9.4% (5.3-16.5) and 94% (95% confidence interval, 70-100) of the
      patients (15 of 16) had > or =4 SNPs. In group B, median (range) RILA was 25.7%
      (20.2-43.2) and 33% (95% confidence interval, 13-59) of patients (6 of 18) had >
      or =4 SNPs (P < 0.001). CONCLUSIONS: The results of this study suggest that
      patients with severe RIS possess 4 or more SNPs in candidate genes and low
      radiation-induced CD8 lymphocyte apoptosis in vitro.

PMID- 18829511
TI  - Zoledronic acid markedly improves bone mineral density for patients with
      monoclonal gammopathy of undetermined significance and bone loss.
AB  - PURPOSE: Patients with monoclonal gammopathy of undetermined significance (MGUS)
      have increased rates of bone resorption, osteopenia, osteoporosis, and risk of
      fractures. This study was undertaken to determine the efficacy and safety of
      zoledronic acid for patients with MGUS and enhanced bone loss. EXPERIMENTAL
      DESIGN: In this phase II open-label study, 54 patients with MGUS and osteopenia
      or osteoporosis were administered zoledronic acid 4 mg i.v. at 0, 6, and 12
      months. The primary efficacy end point was bone mineral density, assessed using a
      dual-energy X-ray absorptiometry scan in the lumbar (L)-spine done at screening
      and at 13 months (1 month after the final zoledronic acid infusion). RESULTS: At
      study end for all patients (N = 54), L-spine T-scores improved by a median of
      +0.27 (range, -0.38 to +3.91), corresponding to a median increase in bone mineral
      density of +15.0% (range, -18.0% to +1,140.0%; P < 0.0001). Hip T-scores improved
      by a median of +0.10 (range, -2.40 to +2.03), corresponding to a median increase
      of +6.0% (range, -350.0% to +165.0%). During the study, no new fractures,
      osteonecrosis of the jaw, or significant renal adverse events were reported.
      CONCLUSIONS: Zoledronic acid administered i.v. at a dosage of 4 mg every 6 months
      for three doses total was well-tolerated and substantially improved bone mineral
      density for patients with MGUS and bone loss. Zoledronic acid may be effective
      for the prevention of new fractures in this high-risk population.

PMID- 18829512
TI  - Phase I study of epigenetic modulation with 5-azacytidine and valproic acid in
      patients with advanced cancers.
AB  - PURPOSE: 5-Azacytidine (5-AZA) is a DNA-hypomethylating agent. Valproic acid is a
      histone deacetylase inhibitor. Combining hypomethylating agents and histone
      deacetylase inhibitors produces synergistic anticancer activity in vitro and in
      vivo. On the basis of this evidence, we conducted a phase I study of the
      combination of 5-AZA and valproic acid in patients with advanced cancers.
      EXPERIMENTAL DESIGN: 5-AZA was administered s.c. daily for 10 days. Valproic acid
      was given orally daily with a goal to titrate to plasma levels of 75 to 100
      mug/mL (therapeutic for seizures). Cycles were 28 days long. 5-AZA was started at
      20 mg/m(2) and escalated using an adaptive algorithm based on the toxicity
      profile in the prior cohort (6 + 6 design). Peripheral blood mononuclear cell
      global DNA methylation and histone H3 acetylation were estimated with the long
      interspersed nucleotide elements pyrosequencing assay and Western blots,
      respectively, on days 1 and 10 of each cycle when patients agreed to provide
      them. RESULTS: Fifty-five patients were enrolled. Median age was 60 years (range,
      12-77 years). The maximum tolerated dose was 75 mg/m(2) of 5-AZA in combination
      with valproic acid. Dose-limiting toxicities were neutropenic fever and
      thrombocytopenia, which occurred at a dose of 94 mg/m(2) of 5-AZA. Stable disease
      lasting 4 to 12 months (median, 6 months) was observed in 14 patients (25%). A
      significant decrease in global DNA methylation and induction of histone
      acetylation were observed. CONCLUSION: The combination of 5-AZA and valproic acid
      is safe at doses up to 75 mg/m(2) for 5-AZA in patients with advanced
      malignancies.

PMID- 18829513
TI  - Circulating tumor cells predict survival benefit from treatment in metastatic
      castration-resistant prostate cancer.
AB  - PURPOSE: A method for enumerating circulating tumor cells (CTC) has received
      regulatory clearance. The primary objective of this prospective study was to
      establish the relationship between posttreatment CTC count and overall survival
      (OS) in castration-resistant prostate cancer (CRPC). Secondary objectives
      included determining the prognostic utility of CTC measurement before initiating
      therapy, and the relationship of CTC to prostate-specific antigen (PSA) changes
      and OS at these and other time points. EXPERIMENTAL DESIGN: Blood was drawn from
      CRPC patients with progressive disease starting a new line of chemotherapy before
      treatment and monthly thereafter. Patients were stratified into predetermined
      Favorable or Unfavorable groups (<5 and > or =5 CTC/7.5mL). RESULTS: Two hundred
      thirty-one of 276 enrolled patients (84%) were evaluable. Patients with
      Unfavorable pretreatment CTC (57%) had shorter OS (median OS, 11.5 versus 21.7
      months; Cox hazard ratio, 3.3; P < 0.0001). Unfavorable posttreatment CTC counts
      also predicted shorter OS at 2 to 5, 6 to 8, 9 to 12, and 13 to 20 weeks (median
      OS, 6.7-9.5 versus 19.6-20.7 months; Cox hazard ratio, 3.6-6.5; P < 0.0001). CTC
      counts predicted OS better than PSA decrement algorithms at all time points; area
      under the receiver operator curve for CTC was 81% to 87% and 58% to 68% for 30%
      PSA reduction (P = 0.0218). Prognosis for patients with (a) Unfavorable baseline
      CTC who converted to Favorable CTC improved (6.8 to 21.3 months); (b) Favorable
      baseline CTC who converted to Unfavorable worsened (>26 to 9.3 months).
      CONCLUSIONS: CTC are the most accurate and independent predictor of OS in CRPC.
      These data led to Food and Drug Administration clearance of this assay for the
      evaluation of CRPC.

PMID- 18829514
TI  - A phase I trial of pemetrexed plus gemcitabine given biweekly with B-vitamin
      support in solid tumor malignancies or advanced epithelial ovarian cancer.
AB  - PURPOSE: To determine the maximally tolerated dose (MTD) of biweekly pemetrexed
      with gemcitabine plus B(12) and folate supplementation in patients with advanced
      solid tumors and ovarian cancer. EXPERIMENTAL DESIGN: Patients with no prior
      pemetrexed or gemcitabine therapy enrolled in cohorts of three, expanding to six
      if dose-limiting toxicity (DLT) was observed. Pemetrexed, escalated from to 700
      mg/m(2), was given before gemcitabine 1,500 mg/m(2) every 14 days. DLTs were
      grade 4 neutropenia lasting >7 days or febrile neutropenia, grade 4 or 3
      thrombocytopenia (with bleeding), grade > or =3 nonhematologic toxicity, or
      treatment delay of > or =1 week due to unresolved toxicity. RESULTS: The ovarian
      cancer cohort enrolled 24 patients with unlimited prior cytotoxic chemotherapies.
      MTD was observed at pemetrexed 600 mg/m(2), with 2 of 9 patients experiencing
      DLT. Most common grade 3 to 4 toxicities per patient were neutropenia (83%),
      leukopenia (67%), lymphopenia (73%), and febrile neutropenia (12%). Median cycle
      per patient was 8 (range, 1-16). Six of 21 (28%) patients had confirmed partial
      responses. Study protocol was modified for the solid tumor cohort (n = 30) to
      enroll patients with two or more prior cytotoxic regimens. MTD was observed at
      pemetrexed 500 mg/m(2), with 1 of 9 patients experiencing DLT. Most common grade
      3 to 4 toxicities per patient were neutropenia (63%), lymphopenia (43%),
      leukopenia (70%) and febrile neutropenia (6.6%). Median cycle per patient was 4
      (range, 1-20). Three of 29 (10.3%) response-evaluable patients had confirmed
      partial responses: 2 squamous cell carcinomas of head and neck and 1
      nasopharyngeal cancer. CONCLUSION: MTDs for the solid tumor and ovarian cancer
      cohorts were reached at pemetrexed 500 and 600 mg/m(2), respectively, given
      biweekly with gemcitabine 1,500 mg/m(2).

PMID- 18829516
TI  - Phase I trial of erlotinib combined with cisplatin and radiotherapy for patients
      with locally advanced cervical squamous cell cancer.
AB  - PURPOSE: This phase I trial was aimed to determine the maximum tolerated dose and
      related toxicity of erlotinib (E) when administered concurrently with standard
      chemoradiation (CRT) for cervical cancer. EXPERIMENTAL DESIGN: In a modified
      Fibonacci design, the study aimed to study three cohorts of at least three
      patients receiving escalating doses of erlotinib (50/100/150 mg) combined with
      cisplatin (40 mg/m(2), weekly, 5 cycles) and radiotherapy (external beam 4,500
      cGy in 25 fractions, followed by 4 fractions/600 cGy/weekly of brachytherapy) in
      squamous cell cervical carcinoma patients, stage IIB to IIIB. RESULTS: Fifteen
      patients were enrolled, 3 at dose level (DL) 50 mg, 4 at DL 100 mg, and 8 at DL
      150 mg. Patients presented median age 47 (36-59), stage IIB (46.2%) and IIIB
      (53.8%). Overall, E+CRT was well-tolerated. Three patients did not complete the
      planned schedule. One patient at DL 100 mg withdrew informed consent due to grade
      2 rash; at DL 150 mg, 1 patient presented Raynaud's Syndrome and had C
      interrupted, and another patient presented grade 4 hepatotoxicity. The latter was
      interpreted as dose limiting toxicity and a new cohort of 150 mg was started. No
      further grade 4 toxicity occurred. Grade 3 toxicity occurred in 6 cases: diarrhea
      in 3 patients, rash in 2 patients, and leukopenia in 1 patient. E+CRT did not
      lead to limiting in-field toxicity. CONCLUSIONS: E+CRT is feasible to locally
      advanced squamous cell cervical cancer and is well tolerated. The maximum
      tolerated dose has been defined as 150 mg. To the best of our knowledge, this is
      the first report of a combination of erlotinib, cisplatin, and pelvic
      radiotherapy.

PMID- 18829515
TI  - Fluorescence in situ hybridization subgroup analysis of TRIBUTE, a phase III
      trial of erlotinib plus carboplatin and paclitaxel in non-small cell lung cancer.
AB  - PURPOSE: TRIBUTE was a phase III trial evaluating the addition of erlotinib to
      carboplatin and paclitaxel as a first-line treatment for advanced non-small cell
      lung cancer that did not meet its primary end point of improving overall
      survival. Here, we assess the value of using epidermal growth factor receptor
      (EGFR) gene copy number in tumor biopsy samples, as determined by fluorescence in
      situ hybridization (FISH), as a predictor of treatment outcome. METHODS: EGFR
      FISH analysis was done using LSI EGFR SpectrumOrange/CEP7 SpectrumGreen probe.
      RESULTS: Of 275 samples, 245 (89.1%) were successfully analyzed by FISH. One
      hundred (40.8%) of patients were EGFR FISH(+). Median overall survival was not
      different between FISH(+) and FISH(-) patients in either the
      chemotherapy+erlotinib arm or the chemotherapy+placebo arm. In FISH(+) patients,
      median time to progression (TTP) was 6.3 months in the erlotinib arm versus 5.8
      months in the placebo arm (hazard ratio, 0.59; 95% confidence interval, 0.35
      0.99; P = 0.0430); in FISH(-) patients, median TTP was 4.6 months versus 6.0
      months (hazard ratio, 1.42; 95% confidence interval, 0.95-2.14; P = 0.0895;
      treatment interaction test, P = 0.007). After 6 months of treatment, a notable
      separation of the TTP curves in favor of erlotinib emerged. Objective response
      rates were 11.6% versus 29.8% in FISH(+) patients (chemotherapy+erlotinib arm
      versus chemotherapy+placebo arm; P = 0.0495) and 21.8% versus 25.4%,
      respectively, for FISH(-) patients (P = 0.6954). CONCLUSIONS: EGFR gene copy
      number by FISH did not predict survival benefit. However, among EGFR FISH(+)
      patients, TTP was longer in patients who received erlotinib and continued to
      receive it after completing first-line therapy.

PMID- 18829517
TI  - Letrozole is superior to anastrozole in suppressing breast cancer tissue and
      plasma estrogen levels.
AB  - PURPOSE: To evaluate the influence of the third-generation aromatase inhibitor
      letrozole (Femara) on breast cancer tissue levels of estrone (E(1)), estradiol
      (E(2)), and estrone sulfate (E(1)S) in postmenopausal women undergoing primary
      treatment for locally advanced estrogen receptor/progesterone receptor-positive
      breast cancers. EXPERIMENTAL DESIGN: Breast cancer tissue samples were collected
      before and following 4 months of neoadjuvant therapy with letrozole (2.5 mg
      o.d.), and tissue estrogen levels measured using a highly sensitive RIA after
      high-pressure liquid chromatography purification. RESULTS: Letrozole suppressed
      pretreatment tumor levels of E(2), E(1), and E(1)S by 97.6%, 90.7%, and 90.1%,
      respectively. These data reveal that letrozole suppresses tissue estrogen levels
      significantly below what has previously been recorded with anastrozole (89.0%,
      83.4%, and 72.9% suppression, respectively) using the same methods. To confirm
      the differential effect of letrozole and anastrozole on each plasma estrogen
      fraction, we re-analyzed plasma samples obtained from a previous intrapatient
      cross-over study comparing letrozole and anastrozole using an improved RIA
      (detection limits of 0.67, 1.14, and 0.55 pmol/L for E(2), E(1), and E(1)S,
      respectively). Letrozole consistently suppressed each plasma estrogen fraction
      below the levels recorded for anastrozole: E(2) (average suppression by 95.2%
      versus 92.8%; P = 0.018), E(1) (98.8% suppression versus 96.3%; P = 0.003), and
      E(1)S (98.9% suppression versus 95.3%; P = 0.003). CONCLUSION: Our data reveals
      that letrozole (2.5 mg o.d.) is more effective compared with anastrozole (1.0 mg
      o.d.) with respect to tissue as well as plasma estrogen suppression in patients
      with postmenopausal breast cancer.

PMID- 18829518
TI  - Prevention of anastrozole-induced bone loss with monthly oral ibandronate during
      adjuvant aromatase inhibitor therapy for breast cancer.
AB  - PURPOSE: The aromatase inhibitor anastrozole is a highly effective well-tolerated
      treatment for postmenopausal endocrine-responsive breast cancer. However, its use
      is associated with accelerated bone loss and an increase in fracture risk. The
      ARIBON trial is a double-blind, randomized, placebo-controlled study designed to
      evaluate the impact of bisphosphonate treatment on bone mineral density (BMD) in
      women taking anastrozole. EXPERIMENTAL DESIGN: BMD was assessed in 131
      postmenopausal, surgically treated women with early breast cancer at two U.K.
      centers. Of these, 50 patients had osteopenia (T score -1.0 to -2.5) at either
      the hip or lumbar spine. All patients were treated with anastrozole 1 mg once a
      day and calcium and vitamin D supplementation. In addition, osteopenic patients
      were randomized to receive either treatment with ibandronate 150 mg orally every
      month or placebo. RESULTS: After 2 years, osteopenic patients treated with
      ibandronate gained +2.98% (range -8.9, +19.9) and +0.60% (range -9.0, +6.9) at
      the lumbar spine and hip, respectively. Patients treated with placebo, however,
      lost -3.22% (range -16.0, +4.3) at the lumbar spine and -3.90% (range -12.3,
      +7.2) at the hip. The differences between the two treatment arms were
      statistically significant at both sites (P < 0.01). At 12 months, urinary n
      telopeptide, serum c-telopeptide, and serum bone-specific alkaline phosphatase
      levels declined in patients receiving ibandronate (30.9%, 26.3%, and 22.8%,
      respectively) and increased in those taking placebo (40.3%, 34.9%, and 37.0%,
      respectively). CONCLUSIONS: Monthly oral ibandronate improves bone density and
      normalizes bone turnover in patients treated with anastrozole.

PMID- 18829519
TI  - CASP3 polymorphisms and risk of squamous cell carcinoma of the head and neck.
AB  - PURPOSE: Caspase-3 plays a central role in executing cell apoptosis and thus in
      carcinogenesis, but little is known about the role of CASP3 variants in
      susceptibility to SCCHN. EXPERIMENTAL DESIGN: Genotype and haplotypes of the
      first intron (rs4647601:G>T and rs4647602:C>A) and 5'-untranslated region (UTR;
      rs4647603:G>A) of CASP3 (NT_022792.17) were determined for 930 SCCHN patients and
      993 cancer-free controls in a U.S. non-Hispanic white population. Odds ratio (OR)
      and 95% confidence interval (95% CI) were calculated in multivariate logistic
      regression analysis. RESULTS: We found that the CASP3 rs4647601:TT variant
      genotype was associated with an increased risk of SCCHN (adjusted OR, 1.32; 95%
      CI, 1.00-1.73) compared with the GG genotype. This risk was more evident in the
      subgroups of younger (< or =56 years) subjects, males, and never smokers with a
      significant trend for increased risk with increased number of variant T allele (P
      < 0.05 for all). However, these risks were not found for other two SNPs.
      Furthermore, individuals with two copies of haplotypes TCG or GCA were found to
      have a significant increased risk of SCCHN (OR, 1.31; 95% CI, 1.07-1.61) compared
      with the other haplotypes, and this risk was more evident in less advanced
      diseases (OR, 1.45; 95% CI, 1.11-1.89) than in the advanced diseases (OR, 1.22;
      95% CI, 0.96-1.54). CONCLUSIONS: These results suggested that genetic variation
      in CASP3 may contribute to SCCHN risk. Larger studies are needed to confirm our
      findings.

PMID- 18829520
TI  - Prevalence of prehypertension and hypertension and associated risk factors among
      Turkish adults: Trabzon Hypertension Study.
AB  - BACKGROUND: To estimate the prevalence, awareness and control of prehypertension
      (preHT) and hypertension (HT) as defined by JNC-7 criteria in the Trabzon Region
      and its associations with demographic factors (age, sex, obesity, marital status,
      reproductive history in women and level of education), socioeconomic factors
      (household income and occupation), family history of selected medical conditions
      (diabetes, hypertension, obesity and cardiovascular disease), lifestyle factors
      (smoking habits, physical activity and alcohol consumption) in the adult
      population. METHODS: In this cross-sectional survey, a sample of households was
      systematically selected from the central province of Trabzon and its nine towns.
      A total of 4809 adult subjects (2601 women and 2208 men) were included in the
      study. Demographic and socioeconomic factors, family history of selected medical
      conditions, and lifestyle factors were obtained for all participants. Systolic
      blood pressure (BP) and diastolic BP levels were measured for all subjects. The
      persons included in the questionnaire were invited to the local medical centers
      for blood examination between 08:00-10:00 following 12 hours of fasting. The
      levels of serum glucose (FBG), total cholesterol (Total-C), high density
      cholesterol (HDL-C), low density cholesterol (LDL-C) and triglycerides were
      measured with autoanalyzer. Definition and classification of HT was performed
      according to guidelines from the US JNC-7 report. Prevalence, awareness,
      treatment and control of HT were assessed. RESULTS: The prevalences of HT and
      preHT were 44.0% (46.1% in women and 41.6% in men) and 14.5% (12.6% in women and
      16.8% in men), respectively. Overall, only 41% of the hypertensive individuals
      had been previously diagnosed. Furthermore, 54.5% of the hypertensive subjects
      were being treated with antihypertensive drugs (AHD), but only 24.3% of treated
      subjects had their BP adequately controlled. Among all hypertensive subjects
      (known and newly diagnosed), only 5.43% had their BP under control. The
      prevalence of HT increased with age, being highest in the 60- to 69-year-old age
      group (84.4%) but lower again in the 70+ age group. Interestingly, the prevalence
      was 16.9% in the 20-to 29-year old age group. HT was associated positively with
      marital status, parity, cessation of cigarette smoking, and negatively with level
      of education, alcohol consumption, current cigarette use, and physical activity.
      Multinomial logistic regression analysis revealed that HT were significantly
      associated with age, male gender, BMI, low education level, nonsmoking, positive
      family history of selected medical conditions, occupation, and parity.
      CONCLUSIONS: The Trabzon Hypertension Study data indicated that HT is very common
      and is an important health problem in the adult population of Trabzon. Patients
      who are unaware of their status and treated uncontrolled hypertensives are at
      high risk of early cardiovascular morbidity and mortality. To control preHT and
      HT, effective public health education and urgent precautions are needed. The
      precautions include serious health education, a well-balanced diet and increasing
      physical activity.

PMID- 18829522
TI  - Pancreatic stellate cells and pancreatic cancer cells: an unholy alliance.
AB  - Pancreatic cancer--a tumor displaying a particularly abundant stromal reaction-
      is notorious for its poor prognosis. Recent studies, via newly developed
      orthotopic models, provide compelling evidence of an important role for
      pancreatic stellate cells (PSC) in pancreatic cancer progression.
      Characterization of the mechanisms mediating PSC-cancer interactions will lead to
      the development of much needed alternative therapeutic approaches to improve
      disease outcome.

PMID- 18829521
TI  - The history of tumor virology.
AB  - In the century since its inception, the field of tumor virology has provided
      groundbreaking insights into the causes of human cancer. Peyton Rous founded this
      scientific field in 1911 by discovering an avian virus that induced tumors in
      chickens; however, it took 40 years for the scientific community to comprehend
      the effect of this seminal finding. Later identification of mammalian tumor
      viruses in the 1930s by Richard Shope and John Bittner, and in the 1950s by
      Ludwik Gross, sparked the first intense interest in tumor virology by suggesting
      the possibility of a similar causal role for viruses in human cancers. This
      change in attitude opened the door in the 1960s and 1970s for the discovery of
      the first human tumor viruses--EBV, hepatitis B virus, and the papillomaviruses.
      Such knowledge proved instrumental to the development of the first cancer
      vaccines against cancers having an infectious etiology. Tumor virologists
      additionally recognized that viruses could serve as powerful discovery tools,
      leading to revolutionary breakthroughs in the 1970s and 1980s that included the
      concept of the oncogene, the identification of the p53 tumor suppressor, and the
      function of the retinoblastoma tumor suppressor. The subsequent availability of
      more advanced molecular technologies paved the way in the 1980s and 1990s for the
      identification of additional human tumor viruses--human T-cell leukemia virus
      type 1, hepatitis C virus, and Kaposi's sarcoma virus. In fact, current estimates
      suggest that viruses are involved in 15% to 20% of human cancers worldwide. Thus,
      viruses not only have been shown to represent etiologic agents for many human
      cancers but have also served as tools to reveal mechanisms that are involved in
      all human malignancies. This rich history promises that tumor virology will
      continue to contribute to our understanding of cancer and to the development of
      new therapeutic and preventive measures for this disease in the 21st century.

PMID- 18829523
TI  - The mammary progenitor marker CD61/beta3 integrin identifies cancer stem cells in
      mouse models of mammary tumorigenesis.
AB  - The cells of origin and mechanisms that underpin tumor heterogeneity in breast
      cancer are poorly understood. Here, we have examined three mouse models of
      mammary tumorigenesis (MMTV-wnt-1, MMTV-neu, and p53(+/-)) for changes in their
      epithelial cell hierarchy during the preneoplastic and neoplastic stages of tumor
      progression. In preneoplastic tissue, only MMTV-wnt-1 mice showed a perturbation
      in their epithelial subpopulations. In addition to an expanded mammary stem cell
      pool, repopulating cells capable of yielding extensive mammary outgrowths in vivo
      were revealed in the committed luminal progenitor population. These findings
      indicate that wnt-1 activation induces the appearance of aberrant progenitor
      cells, and suggest that both mammary stem and progenitor cells can serve as the
      cellular targets of wnt-1-induced tumorigenesis. In tumors arising in MMTV-wnt-1
      tumors, the luminal epithelial progenitor marker CD61/beta3 integrin identified a
      cancer stem cell (CSC) population that was highly enriched for tumorigenic
      capability relative to the CD61(-) subset. CD61 expression also defined a CSC
      subset in 50% of p53(+/-)-derived tumors. No CSCs, however, could be identified
      in the more homogeneous MMTV-neu/erbB2 model, suggesting an alternative model of
      tumorigenesis. Overall, our findings show the utility of the progenitor marker
      CD61 in the identification of CSCs that sustain specific mammary tumors.

PMID- 18829524
TI  - Mutations in the focal adhesion targeting region of deleted in liver cancer-1
      attenuate their expression and function.
AB  - Deleted in liver cancer-1 (DLC-1) is a RhoGTPase-activating protein (RhoGAP)
      domain containing tumor suppressor that is often down-regulated in various cancer
      types. Previously, we have shown that DLC-1 is recruited to focal adhesions by
      binding to the Src homology 2 domains of tensins and the focal adhesion
      localization is critical for the tumor suppression activity of DLC-1. To
      investigate whether mutations in the focal adhesion targeting (FAT) region might
      occur and attenuate the expression, localization, and function of DLC-1, we have
      first mapped the FAT region to the amino acid residues from 201 to 500, and then
      sequenced cDNAs and genomic DNAs encoding the FAT region from cancer patients.
      Several missense and nonsense mutations were detected. All missense mutations
      were further examined for the potential effect on the function of DLC-1. Although
      these mutations did not seem to affect the focal adhesion localization of DLC-1,
      the activities of suppressing tumor cell growth were impaired in two mutants:
      T301K and S308I. Consistent with the fact that the RhoGAP activity of DLC-1 is
      essential for inhibiting tumor cell growth, the RhoGAP activities were
      significantly reduced in these mutants, suggesting that the FAT region also
      contains a regulatory element for its COOH-terminal RhoGAP domain. Our studies
      have shown that mutations in DLC-1 may lead to loss of function and contribute to
      the tumorigenesis, and have revealed an allosteric regulation site for its RhoGAP
      activity.

PMID- 18829525
TI  - SCL/TAL1 interrupting locus derepresses GLI1 from the negative control of
      suppressor-of-fused in pancreatic cancer cell.
AB  - As a physically binding protein of GLI1 transcription factor, Suppressor-of-Fused
      (SUFU) has been placed in the center of negative regulation of Hedgehog (Hh)
      signaling. SUFU tethers GLI1 in cytoplasm, and in some circumstances, it moves
      into the nucleus in association with GLI1, leading to the suppression of GLI1
      target gene expression by recruiting a corepressor complex. The activated
      transcriptional function of GLI1 is important for cellular proliferation in a
      variety of human cancers. However, it has not been revealed how GLI1 is
      derepressed from SUFU-mediated suppression. Here, we show SCL/TAL1 interrupting
      locus (SIL) product, a cytoplasmic protein overexpressed in pancreatic ductal
      adenocarcinoma (PDA), is responsible for the derepression of GLI1. We found SIL
      associated with the carboxyl terminus of SUFU, one of two distinct GLI1-binding
      domains, and this association was responsible for cytoplasmic tethering of SUFU.
      Overexpressed SIL attenuated SUFU-mediated cytoplasmic tethering and target gene
      suppression of GLI1. Knockdown of SIL in PDA cells conversely induced the nuclear
      accumulation of SUFU in association with GLI1 and the transcriptional suppression
      of GLI1 target genes. Importantly, we also showed that oncogenic K-RAS, and not
      Sonic hedgehog, enhanced the SIL association with the amino-terminus of SUFU, the
      other GLI1-binding domain that led to further increase of nuclear translocation
      of GLI1. These results uncover the role of SIL in derepressing GLI1 from the
      negative control of SUFU, which is a crucial step for activating Hh signaling in
      cancer cells.

PMID- 18829526
TI  - Identification of transformation-related pathways in a breast epithelial cell
      model using a ribonomics approach.
AB  - The aberrant expression of many genes is a common feature in the malignant
      transformation of cells. In mammalian cells, posttranscriptional gene regulatory
      processes are emerging as critical determinants controlling gene expression both
      in physiologic and pathologic conditions. These regulatory mechanisms are
      directed primarily by the interaction of mRNAs with specific RNA-binding proteins
      (RBP). There is an emerging body of data demonstrating that two RBPs, AUF1 and
      HuR, can antagonistically affect the posttranscriptional fate of target mRNAs, as
      well as concurrently bind to common target transcripts. Employing MCT-1 oncogene
      mediated transformation of immortalized breast epithelial MCF10A cells, we
      characterized the largely reciprocal association of these two RBPs with target
      mRNAs and their influence on protein expression vis-a-vis cellular
      transformation. Using a ribonomics approach, we identified mRNAs from cancer
      related pathways whose association with AUF1 and/or HuR were altered when
      comparing immortalized with transformed MCF10A cells. Significantly, we were able
      to show that knockdown of HuR expression using RNA interference reduced anchorage
      independent growth capacity in transformed MCF10A cells and decreased protein
      expression of a number of validated target genes. Our data show that the global
      alterations in binding of HuR and AUF1 with target transcripts have a critical
      role in posttranscriptional regulation of genes encoding proteins involved in
      breast epithelial cell transformation. These findings further support the
      feasibility of using a ribonomics approach for the identification of cancer
      related pathways.

PMID- 18829527
TI  - Activation of signal transducer and activator of transcription 3 through a
      phosphomimetic serine 727 promotes prostate tumorigenesis independent of tyrosine
      705 phosphorylation.
AB  - Aberrantly activated signal transducer and activator of transcription 3 (Stat3)
      is implicated in the development of various human cancers. Y705 phosphorylation
      is conventionally thought to be required for Stat3 signal-dependent activation
      and seems to play an essential role in some malignancies. Recently, it was shown
      that Stat3 is activated through novel and noncanonical mechanisms, including
      phosphorylation at S727. Here, we investigate S727 phosphorylation of Stat3 and
      its subsequent effects in prostate cancer development, independent of Y705
      phosphorylation, using mutated Stat3 in the human prostate cancer cell line
      LNCaP. We show mutation of S727 to the phosphomimetic residue Glu, and
      inactivation of Y705 (Y705F/S727E) resulted in a remarkable growth advantage in
      low-serum, enhanced anchorage-independent growth in soft agar, and increased
      tumorigenicity in nonobese diabetic/severe combined immunodeficient (NOD/SCID)
      mice, possibly by direct activation of downstream proto-oncogenes c-myc, mcl-1,
      and survivin. Y705F/S727E mutant cells were more invasive than Y705F/S727A
      (inactivation of Y705 and S727) mutant cells, and more Y705F/S727E mutant Stat3
      was localized in the nuclei relative to Y705F/S727A mutant Stat3 at the steady
      state. Furthermore, the Y705F/S727E but not the Y705F/S727A mutant induced
      anchorage-independent growth of noncancerous prostate epithelial cells (RWPE-1).
      We further show that Stat3 is phosphorylated at S727 in 65% of malignant prostate
      tissues (n = 20) relative to 25% of normal prostate tissues (n = 4). Moreover,
      there is a positive correlation between phosphoS727-Stat3 expression and Gleason
      score in these prostate cancer tissues (P = 0.05). Our data suggest for the first
      time that S727 phosphorylation is sufficient to activate Stat3, thereby driving
      prostate tumorigenesis independent of Y705 phosphorylation.

PMID- 18829528
TI  - The polycomb gene product BMI1 contributes to the maintenance of tumor-initiating
      side population cells in hepatocellular carcinoma.
AB  - Side population (SP) cell analysis and sorting have been successfully applied to
      hepatocellular carcinoma (HCC) cell lines to identify a minor cell population
      with cancer stem cell properties. However, the molecular mechanisms operating in
      SP cells remain unclear. The polycomb gene product BMI1 plays a central role in
      the self-renewal of somatic stem cells in a variety of tissues and organs and
      seems to be implicated in tumor development. In this study, we determined the
      critical role of BMI1 in the maintenance of cancer stem cells with the SP
      phenotype in HCC cell lines. BMI1 was preferentially expressed in SP cells in
      Huh7 and PLC/PRF/5 HCC cells compared with the corresponding non-SP cells.
      Lentiviral knockdown of BMI1 considerably decreased the number of SP cells in
      both Huh7 and PLC/PRF/5 cells. Long-term culture of purified SP cells resulted in
      a drastic reduction in the SP subpopulation upon the BMI1 knockdown, indicating
      that BMI1 is required for the self-renewal of SP cells in culture. More
      importantly, the BMI1 knockdown abolished the tumor-initiating ability of SP
      cells in nonobese diabetic/severe combined immunodeficiency mice. Derepression of
      the INK4A and ARF genes that are major targets for BMI1 was not necessarily
      associated with impaired self-renewal of SP cells caused by BMI1 knockdown. In
      conclusion, our findings define an important role for BMI1 in the maintenance of
      tumor-initiating SP cells in HCC. BMI1 might be a novel therapeutic target for
      the eradication of cancer stem cells in HCC.

PMID- 18829529
TI  - Prostaglandin E2 regulates tumor angiogenesis in prostate cancer.
AB  - In cancer management, the cyclooxygenase (COX)-targeted approach has shown great
      promise in anticancer therapeutics. However, the use of COX-2 inhibitors has side
      effects and health hazards; thus, targeting its major metabolite prostaglandin
      E(2) (PGE(2))-mediated signaling pathway might be a rational approach for the
      next generation of cancer management. Recent studies on several in vitro and in
      vivo models have revealed that elevated expression of COX-2 correlates with
      prostate tumor growth and angiogenesis. In this study, we have shown the in-depth
      molecular mechanism and the PGE(2) activation of the epidermal growth factor
      receptor and beta3 integrin through E prostanoid 2 (EP2)-mediated and EP4
      mediated pathways, which lead to activator protein-1 (AP-1) activation. Moreover,
      PGE(2) also induces activating transcription factor-4 (ATF-4) activation and
      stimulates cross-talk between ATF-4 and AP-1, which is unidirectional toward AP
      1, which leads to the increased expressions of urokinase-type plasminogen
      activator and vascular endothelial growth factor and, eventually, regulates
      prostate tumor cell motility. In vivo Matrigel angiogenesis assay data revealed
      that PGE(2) induces angiogenesis through EP2 and EP4. Human prostate cancer
      specimen analysis also supported our in vitro and in vivo studies. Our data
      suggest that targeting PGE(2) signaling pathway (i.e., blocking EP2 and EP4
      receptors) might be a rational therapeutic approach for overcoming the side
      effects of COX-2 inhibitors and that this might be a novel strategy for the next
      generation of prostate cancer management.

PMID- 18829530
TI  - Ectopic expression of P-cadherin correlates with promoter hypomethylation early
      in colorectal carcinogenesis and enhanced intestinal crypt fission in vivo.
AB  - P-cadherin is normally expressed in the basal layer of squamous epithelia and
      absent from the healthy intestine and colon. We have previously shown it to be
      expressed in all inflamed, hyperplastic, and dysplastic intestinal and colonic
      mucosa. This study aimed to better understand the mechanisms controlling the
      expression of P-cadherin and the biological effects of its ectopic presence in
      the intestine and colon. We investigated the CpG methylation status of the P
      cadherin (CDH3) promoter and P-cadherin mRNA and protein expression in cases of
      familial and sporadic colorectal cancer (CRC). The CDH3 promoter was
      hypomethylated in colonic aberrant crypt foci, in CRC, and, occasionally, in the
      normal epithelium adjacent to cancer, demonstrating a potential "field effect" of
      cancerization. The hypomethylation was also associated with induction of P
      cadherin expression in the neoplastic colon (P < 0.0001). We then created
      transgenic mice that overexpressed P-cadherin specifically in the intestinal and
      colonic epithelium under the liver fatty acid binding protein promoter. Forced
      ectopic expression of P-cadherin accompanied by indomethacin-induced inflammation
      resulted in a 3-fold higher crypt fission rate within the small and large
      intestines in the homozygous mice compared with the wild-type animals (P < 0.02).
      We conclude that epigenetic demethylation of the P-cadherin promoter in the human
      intestine permits its ectopic expression very early in the colorectal adenoma
      carcinoma sequence and persists during invasive cancer. Induced P-cadherin
      expression, especially in mucosal damage, leads to an increased rate of crypt
      fission, a common feature of clonal expansion in gastrointestinal dysplasia.

PMID- 18829531
TI  - Prolyl isomerase cyclophilin A regulation of Janus-activated kinase 2 and the
      progression of human breast cancer.
AB  - The activation of the Janus-activated kinase 2 (Jak2) tyrosine kinase following
      ligand binding has remained incompletely characterized at the mechanistic level.
      We report that the peptidyl-prolyl isomerase (PPI) cyclophilin A (CypA), which is
      implicated in the regulation of protein conformation, is necessary for the
      prolactin (PRL)-induced activation of Jak2 and the progression of human breast
      cancer. A direct correlation was observed between the levels or activity of CypA
      and the extent of PRL-induced signaling and gene expression. Loss of PRLr-CypA
      binding, following treatment with the PPI inhibitor cyclosporine A (CsA), or
      overexpression of a dominant-negative PRLr mutant (P334A) resulted in a loss of
      PRLr/Jak2-mediated signaling. In vitro, CsA treatment of breast cancer cells
      inhibited their growth, motility, invasion, and soft agar colony formation. In
      vivo, CsA treatment of nude mice xenografted with breast cancer cells induced
      tumor necrosis and completely inhibited metastasis. These studies reveal that a
      CypA-mediated conformational change within the PRLr/Jak2 complex is required for
      PRL-induced transduction and function and indicate that the inhibition of prolyl
      isomerases may be a novel therapeutic strategy in the treatment of human breast
      cancer.

PMID- 18829532
TI  - Breast tumor kinase phosphorylates p190RhoGAP to regulate rho and ras and promote
      breast carcinoma growth, migration, and invasion.
AB  - Breast tumor kinase (Brk), an Src-like nonreceptor tyrosine kinase, is
      overexpressed in breast cancer and several other cancer types. Our previous study
      indicates that Brk promotes cell migration and tumor invasion by phosphorylating
      the focal adhesion protein paxillin. Here, we report the identification of
      p190RhoGAP-A (p190) as a Brk substrate. Brk phosphorylates p190 at the Y(1105)
      residue both in vitro and in vivo, thereby promoting the association of p190 with
      p120RasGAP (p120). As a consequence, Brk stimulates p190 and attenuates p120
      functions, leading to RhoA inactivation and Ras activation, respectively. In
      carcinoma cells expressing high levels of Brk, endogenous Brk functions as a key
      contributor to epidermal growth factor-induced p190 tyrosine phosphorylation. We
      present evidence showing that p190 phosphorylation plays essential roles in both
      migratory and proliferative effects of Brk. Furthermore, disruption of p190
      phosphorylation-induced p190/p120 complex in breast cancer cells abolishes not
      only the abilities of Brk to regulate RhoA and Ras but also the stimulatory
      effects of Brk on proliferation, migration, invasion, transformation, and
      tumorigenicity. Together, our findings reveal a previously unknown function of
      Brk in regulating both RhoA and Ras by phosphorylating p190 and provide evidence
      for the crucial roles of this Brk-elicited signaling pathway in promoting breast
      malignancy.

PMID- 18829533
TI  - Brn-2 represses microphthalmia-associated transcription factor expression and
      marks a distinct subpopulation of microphthalmia-associated transcription factor
      negative melanoma cells.
AB  - The origin of tumor heterogeneity is poorly understood, yet it represents a major
      barrier to effective therapy. In melanoma and in melanocyte development, the
      microphthalmia-associated transcription factor (Mitf) controls survival,
      differentiation, proliferation, and migration/metastasis. The Brn-2 (N-Oct-3,
      POU3F2) transcription factor also regulates melanoma proliferation and is up
      regulated by BRAF and beta-catenin, two key melanoma-associated signaling
      molecules. Here, we show that Brn-2 also regulates invasiveness and directly
      represses Mitf expression. Remarkably, in melanoma biopsies, Mitf and Brn-2 each
      mark a distinct subpopulation of melanoma cells, providing a striking
      illustration of melanoma tumor heterogeneity with implications for melanoma
      therapy.

PMID- 18829535
TI  - Dietary induction of colonic tumors in a mouse model of sporadic colon cancer.
AB  - A defined rodent "new Western diet" (NWD), which recapitulates intake levels of
      nutrients that are major dietary risk factors for human colon cancer, induced
      colonic tumors when fed to wild-type C57Bl/6 mice for 1.5 to 2 years from age 6
      weeks (two-thirds of their life span). Colonic tumors were prevented by elevating
      dietary calcium and vitamin D(3) to levels comparable with upper levels consumed
      by humans, but tumorigenesis was not altered by similarly increasing folate,
      choline, methionine, or fiber, each of which was also at the lower levels in the
      NWD that are associated with risk for colon cancer. The NWD significantly altered
      profiles of gene expression in the flat colonic mucosa that exhibited
      heterogeneity among the mice, but unsupervised clustering of the data and novel
      statistical analyses showed reprogramming of colonic epithelial cells in the flat
      mucosa by the NWD was similar to that initiated by inheritance of a mutant Apc
      allele. The NWD also caused general down-regulation of genes encoding enzymes
      involved in lipid metabolism and the tricarboxylic acid cycle in colonic
      epithelial cells before tumor formation, which was prevented by the
      supplementation of the NWD with calcium and vitamin D(3) that prevented colon
      tumor development, demonstrating profound interaction among nutrients. This mouse
      model of dietary induction of colon cancer recapitulates levels and length of
      exposure to nutrients linked to relative risk for human sporadic colon cancer,
      which represents the etiology of >90% of colon cancer in the United States and
      other Western countries.

PMID- 18829534
TI  - Runx2 transcriptional activation of Indian Hedgehog and a downstream bone
      metastatic pathway in breast cancer cells.
AB  - Runx2, required for bone formation, is ectopically expressed in breast cancer
      cells. To address the mechanism by which Runx2 contributes to the osteolytic
      disease induced by MDA-MB-231 cells, we investigated the effect of Runx2 on key
      components of the "vicious cycle" of transforming growth factor beta (TGFbeta)
      mediated tumor growth and osteolysis. We find that Runx2 directly up-regulates
      Indian Hedgehog (IHH) and colocalizes with Gli2, a Hedgehog signaling molecule.
      These events further activate parathyroid hormone-related protein (PTHrP).
      Furthermore, Runx2 directly regulates the TGFbeta-induced PTHrP levels. A
      subnuclear targeting deficient mutant Runx2, which disrupts TGFbeta-induced Runx2
      Smad interactions, failed to induce IHH and downstream events. In addition, Runx2
      knockdown in MDA-MB-231 inhibited IHH and PTHrP expression in the presence of
      TGFbeta. In vivo blockade of the Runx2-IHH pathway in MDA-MB-231 cells by Runx2
      short hairpin RNA inhibition prevented the osteolytic disease. Thus, our studies
      define a novel role of Runx2 in up-regulating the vicious cycle of metastatic
      bone disease, in addition to Runx2 regulation of genes related to progression of
      tumor metastasis.

PMID- 18829536
TI  - Anterior gradient 2 is expressed and secreted during the development of
      pancreatic cancer and promotes cancer cell survival.
AB  - Pancreatic cancer is a major oncological challenge due to its aggressive growth
      and metastasis. In the current study, we investigated the role of anterior
      gradient 2 (AGR2) in these processes. AGR2 mRNA, as assessed by quantitative real
      time reverse transcription-PCR (Q-RT-PCR), was 14-fold higher in pancreatic
      cancer compared with normal and pancreatitis tissues. Immunohistochemistry
      revealed high expression of AGR2 in neoplastic cells with 98% (56 of 57)
      positivity on pancreatic cancer and minimal staining in normal and pancreatitis
      tissues. AGR2 was also expressed in early pancreatic intraepithelial neoplastic
      lesions. RT-PCR and Western blotting showed elevated AGR2 expression in seven of
      nine pancreatic cancer cell lines. AGR2, as detected in conditioned media from
      cancer cells, indicated that it was secreted. The influence of AGR2 on pancreatic
      cancer cells was evaluated by silencing with small interfering RNA and short
      hairpin RNA. Silencing of AGR2 significantly reduced cell proliferation (MTS
      assay) and invasion (Boyden chamber assay) and improved gemcitabine sensitivity
      (fluorescence-activated cell sorting analysis). Conditioned media from cells in
      which AGR2 was silenced had a reduced ability to stimulate proliferation of
      pancreatic cancer cells, suggesting that secreted AGR2 was active. In vivo,
      silencing of AGR2 in MPanc-96 cells led to a significant reduction of tumor
      growth and increased the effectiveness of gemcitabine treatments in orthotopic
      tumor models evaluated by noninvasive bioluminescence imaging. In summary, AGR2
      is expressed and secreted during pancreatic cancer development and plays an
      important role in cancer cell growth and survival. These observations suggest
      that AGR2 may be a useful molecular target in pancreatic cancer.

PMID- 18829537
TI  - SLITs suppress tumor growth in vivo by silencing Sdf1/Cxcr4 within breast
      epithelium.
AB  - The genes encoding Slits and their Robo receptors are silenced in many types of
      cancer, including breast, suggesting a role for this signaling pathway in
      suppressing tumorigenesis. The molecular mechanism underlying these tumor
      suppressive effects has not been delineated. Here, we show that loss of Slits, or
      their Robo1 receptor, in murine mammary gland or human breast carcinoma cells
      results in coordinate up-regulation of the Sdf1 and Cxcr4 signaling axis,
      specifically within mammary epithelium. This is accompanied by hyperplastic
      changes in cells and desmoplastic alterations in the surrounding stroma. A
      similar inverse correlation between Slit and Cxcr4 expression is identified in
      human breast tumor tissues. Furthermore, we show in a xenograft model that Slit
      overexpression down-regulates CXCR4 and dominantly suppresses tumor growth. These
      studies classify Slits as negative regulators of Sdf1 and Cxcr4 and identify a
      molecular signature in hyperplastic breast lesions that signifies inappropriate
      up-regulation of key prometastatic genes.

PMID- 18829538
TI  - Suppression of prostate cancer nodal and systemic metastasis by blockade of the
      lymphangiogenic axis.
AB  - Lymph node involvement denotes a poor outcome for patients with prostate cancer.
      Our group, along with others, has shown that initial tumor cell dissemination to
      regional lymph nodes via lymphatics also promotes systemic metastasis in mouse
      models. The aim of this study was to investigate the efficacy of suppressive
      therapies targeting either the angiogenic or lymphangiogenic axis in inhibiting
      regional lymph node and systemic metastasis in subcutaneous and orthotopic
      prostate tumor xenografts. Both androgen-dependent and more aggressive androgen
      independent prostate tumors were used in our investigations. Interestingly, we
      observed that the threshold for dissemination is lower in the vascular-rich
      prostatic microenvironment compared with subcutaneously grafted tumors. Both
      vascular endothelial growth factor-C (VEGF-C) ligand trap (sVEGFR-3) and antibody
      directed against VEGFR-3 (mF4-31C1) significantly reduced tumor lymphangiogenesis
      and metastasis to regional lymph nodes and distal vital organs without
      influencing tumor growth. Conversely, angiogenic blockade by short hairpin RNA
      against VEGF or anti-VEGFR-2 antibody (DC101) reduced tumor blood vessel density,
      significantly delayed tumor growth, and reduced systemic metastasis, although it
      was ineffective in reducing lymphangiogenesis or nodal metastasis. Collectively,
      these data clarify the utility of vascular therapeutics in prostate tumor growth
      and metastasis, particularly in the context of the prostate microenvironment. Our
      findings highlight the importance of lymphangiogenic therapies in the control of
      regional lymph node and systemic metastasis.

PMID- 18829540
TI  - A double-negative feedback loop between ZEB1-SIP1 and the microRNA-200 family
      regulates epithelial-mesenchymal transition.
AB  - Epithelial to mesenchymal transition occurs during embryologic development to
      allow tissue remodeling and is proposed to be a key step in the metastasis of
      epithelial-derived tumors. The miR-200 family of microRNAs plays a major role in
      specifying the epithelial phenotype by preventing expression of the transcription
      repressors, ZEB1/deltaEF1 and SIP1/ZEB2. We show here that miR-200a, miR-200b,
      and the related miR-429 are all encoded on a 7.5-kb polycistronic primary miRNA
      (pri-miR) transcript. We show that the promoter for the pri-miR is located within
      a 300-bp segment located 4 kb upstream of miR-200b. This promoter region is
      sufficient to confer expression in epithelial cells and is repressed in
      mesenchymal cells by ZEB1 and SIP1 through their binding to a conserved pair of
      ZEB-type E-box elements located proximal to the transcription start site. These
      findings establish a double-negative feedback loop controlling ZEB1-SIP1 and miR
      200 family expression that regulates cellular phenotype and has direct relevance
      to the role of these factors in tumor progression.

PMID- 18829539
TI  - Hepatocyte growth factor and sonic Hedgehog expression in cerebellar neural
      progenitor cells costimulate medulloblastoma initiation and growth.
AB  - Medulloblastomas are malignant brain tumors that arise by transformation of
      neural progenitor cells in the cerebellum in children. Treatment-related
      neurotoxicity has created a critical need to identify signaling molecules that
      can be targeted therapeutically to maximize tumor growth suppression and minimize
      collateral neurologic injury. In genetically engineered mice, activation of Sonic
      Hedgehog (Shh) signaling in neural stem cells in the developing cerebellum
      induces medulloblastomas. Hepatocyte growth factor (HGF) and its cell surface
      receptor c-Met are highly expressed in human medulloblastomas, and elevated
      levels of c-Met and HGF mRNA predict an unfavorable prognosis for patients. HGF
      is neuroprotective for cerebellar granule cells and promotes growth of human
      medulloblastoma cells in culture and in murine xenografts. We modeled the ability
      of HGF to induce medulloblastomas in mice using a version of the RCAS/tv-a system
      that allows gene transfer to cerebellar neural progenitors during their postnatal
      expansion phase when these cells are highly susceptible to transformation. Here,
      we report a high frequency of medulloblastoma formation in mice after postnatal
      expression of HGF in cooperation with Shh. Some tumors showed neurocytic
      differentiation similar to that in human nodular medulloblastomas with activated
      Shh signaling. Systemic administration of a monoclonal antibody against HGF
      prolonged survival of mice bearing Shh + HGF-induced medulloblastomas by
      stimulating apoptosis. These findings indicate a role for HGF in medulloblastoma
      initiation and growth and show efficacy of HGF-targeted therapy in a mouse model
      of endogenously arising tumors.

PMID- 18829541
TI  - Regulation of estrogenic effects by beclin 1 in breast cancer cells.
AB  - Beclin 1 is an essential mediator of autophagy and a regulator of cell growth and
      cell death. We examined the effect of Beclin 1 overexpression on the action of
      estradiol (E(2)) and two antiestrogens, raloxifene and 4-hydroxytamoxifen, in
      estrogen receptor alpha (ERalpha)-positive MCF-7 breast cancer cells. [(3)H]
      thymidine incorporation studies showed that Beclin 1-overexpressing cells (MCF-7
      x beclin) had a lower proliferative response to E(2) compared with cells
      transfected with vector control (MCF-7 x control). There was only a 35% increase
      in [(3)H]-thymidine incorporation, after 24 hours of E(2) treatment of MCF-7 x
      beclin cells compared with untreated cells, whereas this increase was 2-fold for
      MCF-7 x control cells. E(2)-induced changes in the expression of early-response
      genes were examined by real-time quantitiative PCR. There were significant
      differences in the pattern of expression of E(2)-induced genes c-myc, c-fos, Erg
      1, and Nur77 between MCF-7 x beclin and MCF-7 x control cells two hours after
      treatment. Although E(2)-induced growth of MCF-7 x control cells was completely
      inhibited by 500 nmol/L raloxifene or 500 nmol/L 4-hydroxytamoxifen, these
      concentrations of antiestrogens had no significant effect on the growth of MCF-7
      x beclin cells. Confocal microscopic and coimmunoprecipitation studies showed
      evidence for colocalization and association of Beclin 1 and ERalpha. In addition,
      E(2) caused a decrease in Akt phosphorylation in MCF-7 x beclin cells, compared
      with a 3-fold increase in MCF-7 cells, five minutes after treatment. These
      results indicate that Beclin 1 can down-regulate estrogenic signaling and growth
      response, and contribute to the development of antiestrogen resistance. This
      observation might be useful to define and overcome antiestrogen resistance of
      breast cancer.

PMID- 18829542
TI  - Senescence-associated exosome release from human prostate cancer cells.
AB  - Males of advanced age represent a rapidly growing population at risk for prostate
      cancer. In the contemporary setting of earlier detection, a majority of prostate
      carcinomas are still clinically localized and often treated using radiation
      therapy. Our recent studies have shown that premature cellular senescence, rather
      than apoptosis, accounts for most of the clonogenic death induced by clinically
      relevant doses of irradiation in prostate cancer cells. We show here that this
      treatment-induced senescence was associated with a significantly increased
      release of exosome-like microvesicles. In premature senescence, this novel
      secretory phenotype was dependent on the activation of p53. In addition, the
      release of exosome-like microvesicles also increased during proliferative
      senescence in normal human diploid fibroblasts. These data support the hypothesis
      that senescence, initiated either by telomere attrition (e.g., aging) or DNA
      damage (e.g., radiotherapy), may induce a p53-dependent increase in the
      biogenesis of exosome-like vesicles. Ultrastructural analysis and RNA
      interference-mediated knockdown of Tsg101 provided significant evidence that the
      additional exosomes released by prematurely senescent prostate cancer cells were
      principally derived from multivesicular endosomes. Moreover, these exosomes were
      enriched in B7-H3 protein, a recently identified diagnostic marker for prostate
      cancer, and an abundance of what has recently been termed "exosomal shuttle RNA."
      Our findings are consistent with the proposal that exosomes can transfer cargos,
      with both immunoregulatory potential and genetic information, between cells
      through a novel mechanism that may be recruited to increase exosome release
      during accelerated and replicative cellular senescence.

PMID- 18829543
TI  - Tbx3 represses E-cadherin expression and enhances melanoma invasiveness.
AB  - The T-box transcription factors Tbx2 and Tbx3 are overexpressed in many cancers
      and in melanoma promote proliferation by actively suppressing senescence. Whether
      they also contribute to tumor progression via other mechanisms is not known.
      Here, we identify a novel role for these factors, providing evidence that Tbx3,
      and potentially Tbx2, directly repress the expression of E-cadherin, a
      keratinocyte-melanoma adhesion molecule whose loss is required for the
      acquisition of an invasive phenotype. Overexpression of Tbx2 and Tbx3 in melanoma
      cells down-regulates endogenous E-cadherin expression, whereas depletion of Tbx3,
      but not Tbx2, increases E-cadherin mRNA and protein levels and decreases melanoma
      invasiveness in vitro. Consistent with these observations, in melanoma tissue,
      Tbx3 and E-cadherin expression are inversely correlated. Depletion of Tbx3 also
      leads to substantial up-regulation of Tbx2. The results suggest that Tbx2 and
      Tbx3 may play a dual role during the radial to vertical growth phase transition
      by both inhibiting senescence via repression of p21(CIP1) expression, and
      enhancing melanoma invasiveness by decreasing E-cadherin levels.

PMID- 18829544
TI  - Cell cycle-dependent variation of a CD133 epitope in human embryonic stem cell,
      colon cancer, and melanoma cell lines.
AB  - CD133 (Prominin1) is a pentaspan transmembrane glycoprotein expressed in several
      stem cell populations and cancers. Reactivity with an antibody (AC133) to a
      glycoslyated form of CD133 has been widely used for the enrichment of cells with
      tumor-initiating activity in xenograph transplantation assays. We have found by
      fluorescence-activated cell sorting that increased AC133 reactivity in human
      embryonic stem cells, colon cancer, and melanoma cells is correlated with
      increased DNA content and, reciprocally, that the least reactive cells are in the
      G(1)-G(0) portion of the cell cycle. Continued cultivation of cells sorted on the
      basis of high and low AC133 reactivity results in a normalization of the cell
      reactivity profiles, indicating that cells with low AC133 reactivity can generate
      highly reactive cells as they resume proliferation. The association of AC133 with
      actively cycling cells may contribute to the basis for enrichment for tumor
      initiating activity.

PMID- 18829545
TI  - Dual roles for coactivator activator and its counterbalancing isoform coactivator
      modulator in human kidney cell tumorigenesis.
AB  - Coactivator activator (CoAA) has been reported to be a coactivator that regulates
      steroid receptor-mediated transcription and alternative RNA splicing. Herein, we
      show that CoAA is a dual-function coregulator that inhibits G(1)-S transition in
      human kidney cells and suppresses anchorage-independent growth and xenograft
      tumor formation. Suppression occurs in part by down-regulating c-myc and its
      downstream effectors ccnd1 and skp2 and causing accumulation of p27/Kip1 protein.
      In this cellular setting, CoAA directly represses the proto-oncogene c-myc by
      recruiting HDAC3 protein and decreasing both the acetylation of histone H3 and
      the presence of RNA polymerase II on the c-myc promoter. Interestingly, a
      splicing isoform of CoAA, coactivator modulator (CoAM), antagonizes CoAA-induced
      G(1)-S transition and growth inhibition by negatively regulating the mRNA levels
      of the endogenous CoAA isoform. In addition, we found that expression of CoAA
      protein is significantly decreased in human renal cell carcinoma compared with
      normal kidney. Our study presents evidence that CoAA is a potential tumor
      suppressor in renal carcinoma and that CoAM is a counterbalancing splice isoform.
      This is, thus far, the only example of a nuclear receptor coregulator involved in
      suppression of kidney cancer and suggests potentially significant new roles for
      coregulators in renal cancer biology.

PMID- 18829546
TI  - Glucagon-like peptide-2 does not modify the growth or survival of murine or human
      intestinal tumor cells.
AB  - Glucagon-like peptide-2 (GLP-2) secreted from enteroendocrine cells exerts
      proabsorptive, regenerative, and cytoprotective actions in the normal and injured
      gut epithelium. Hence, sustained GLP-2 receptor (GLP-2R) activation represents a
      strategy under investigation for the prevention and treatment of chemotherapy
      induced mucositis. Nevertheless, the consequences of increased GLP-2R signaling
      for the growth and survival of intestinal tumor cells remain poorly understood.
      We studied the proliferative and cytoprotective actions of GLP-2 in human colon
      cancer cells stably transfected with the GLP-2R and in nude mice harboring GLP
      2R(+) human colon cancer cells. The importance of the GLP-2R for tumor growth was
      also examined in Apc(Min/+) mice chronically treated with exogenous GLP-2 and in
      Apc(Min/+):Glp2r(-/-) mice. GLP-2 increased cyclic AMP accumulation and produced
      cell-specific activation of growth and survival pathways in DLD-1, SW480, and
      HT29 cells. However, GLP-2 did not stimulate cell growth or attenuate
      cycloheximide-, LY294002-, indomethacin-, or chemotherapy-induced cytotoxicity in
      vitro. Moreover, chronic GLP-2 administration had no effect on the growth of
      human colon cancer cell xenografts in nude mice in vivo. Daily GLP-2 treatment
      for 7 weeks increased growth of normal gut mucosa but did not increase the number
      or size of polyps in Apc(Min/+) mice, and genetic disruption of the Glp2r gene in
      Apc(Min/+) mice did not modify polyp size or number. Taken together, although GLP
      2R activation engages signaling pathways promoting cell proliferation and
      cytoprotection in the normal gut epithelium, sustained direct or indirect
      modulation of GLP-2R signaling does not modify intestinal tumor cell growth or
      survival.

PMID- 18829548
TI  - Disruption of NAD(P)H:quinone oxidoreductase 1 gene in mice leads to radiation
      induced myeloproliferative disease.
AB  - NAD(P)H:quinone oxidoreductase 1 null (NQO1(-/-)) mice exposed to 3 Gy of gamma
      radiation showed an increase in neutrophils, bone marrow hypercellularity, and
      enlarged lymph nodes and spleen. The spleen showed disrupted follicular
      structure, loss of red pulp, and granulocyte and megakarocyte invasion. Blood and
      histologic analysis did not show any sign of infection in mice. These results
      suggested that exposure of NQO1(-/-) mice to gamma-radiation led to
      myeloproliferative disease. Radiation-induced myeloproliferative disease was
      observed in 74% of NQO1(-/-) mice as compared with none in wild-type (WT) mice.
      NQO1(-/-) mice exposed to gamma-radiation also showed lymphoma tissues (32%) and
      lung adenocarcinoma (84%). In contrast, only 11% WT mice showed lymphoma and none
      showed lung adenocarcinoma. Exposure of NQO1(-/-) mice to gamma-radiation
      resulted in reduced apoptosis in granulocytes and lack of induction of p53, p21,
      and Bax. NQO1(-/-) mice also showed increased expression of myeloid
      differentiation factors CCAAT/enhancer binding protein alpha (C/EBPalpha) and
      Pu.1. Intriguingly, exposure of NQO1(-/-) mice to gamma-radiation failed to
      induce C/EBPalpha and Pu.1, as was observed in WT mice. These results suggest
      that decreased p53/apoptosis and increased Pu.1 and C/EBPalpha led to myeloid
      hyperplasia in NQO1(-/-) mice. The lack of induction of apoptosis and
      differentiation contributed to radiation-induced myeloproliferative disease in
      NQO1(-/-) mice.

PMID- 18829547
TI  - Lapatinib (Tykerb, GW572016) reverses multidrug resistance in cancer cells by
      inhibiting the activity of ATP-binding cassette subfamily B member 1 and G member
      2.
AB  - Lapatinib is active at the ATP-binding site of tyrosine kinases that are
      associated with the human epidermal growth factor receptor (Her-1 or ErbB1) and
      Her-2. It is conceivable that lapatinib may inhibit the function of ATP-binding
      cassette (ABC) transporters by binding to their ATP-binding sites. The aim of
      this study was to investigate the ability of lapatinib to reverse tumor multidrug
      resistance (MDR) due to overexpression of ABC subfamily B member 1 (ABCB1) and
      ABC subfamily G member 2 (ABCG2) transporters. Our results showed that lapatinib
      significantly enhanced the sensitivity to ABCB1 or ABCG2 substrates in cells
      expressing these transporters, although a small synergetic effect was observed in
      combining lapatinib and conventional chemotherapeutic agents in parental
      sensitive MCF-7 or S1 cells. Lapatinib alone, however, did not significantly
      alter the sensitivity of non-ABCB1 or non-ABCG2 substrates in sensitive and
      resistant cells. Additionally, lapatinib significantly increased the accumulation
      of doxorubicin or mitoxantrone in ABCB1- or ABCG2-overexpressing cells and
      inhibited the transport of methotrexate and E(2)17betaG by ABCG2. Furthermore,
      lapatinib stimulated the ATPase activity of both ABCB1 and ABCG2 and inhibited
      the photolabeling of ABCB1 or ABCG2 with [(125)I]iodoarylazidoprazosin in a
      concentration-dependent manner. However, lapatinib did not affect the expression
      of these transporters at mRNA or protein levels. Importantly, lapatinib also
      strongly enhanced the effect of paclitaxel on the inhibition of growth of the
      ABCB1-overexpressing KBv200 cell xenografts in nude mice. Overall, we conclude
      that lapatinib reverses ABCB1- and ABCG2-mediated MDR by directly inhibiting
      their transport function. These findings may be useful for cancer combinational
      therapy with lapatinib in the clinic.

PMID- 18829549
TI  - Nuclear survivin abrogates multiple cell cycle checkpoints and enhances viral
      oncolysis.
AB  - Survivin (BIRC5) promotes cell division and survival with roles as chromosomal
      passenger protein and inhibitor of apoptosis protein (IAP). It is overexpressed
      in many cancers and is associated with resistance to chemotherapy and radiation.
      Previously, we showed that expression of survivin within the nucleus of HeLa
      cells accelerates its degradation and blocks apoptosis inhibition without
      affecting localization during mitosis. Here, we have investigated the effects of
      survivin on cell cycle control and potential therapeutic consequences using HeLa
      and IGROV1 cells expressing wild-type and nuclear-targeted survivin. We show that
      overexpression of survivin, especially within the nucleus, increases control over
      G(1)-S checkpoint via increased nuclear accumulation of cyclin D and cyclin
      dependent kinase 4 and subsequent pRb phosphorylation. We investigated the
      influence of survivin on the activity of the E1A CR2-deleted oncolytic adenovirus
      dl922-947, which depends critically on an aberrant G(1)-S checkpoint. Nuclear
      expression of survivin augments virus-induced S-phase induction and increases
      viral protein expression and overall viral replication. There is a consequent
      increase in antitumor activity both in vitro and in vivo. The increased dl922-947
      activity is restricted to malignant cells and is not associated with induction of
      apoptosis, nor does it rely on the role of survivin as an IAP. In addition, we
      observe the appearance of a large >or=4N population coincident with multiple
      mitotic defects in dl922-947-infected cells, both of which are significantly
      increased by nuclear survivin. This indicates that adenoviral activity is
      facilitated by abrogation of multiple cell cycle checkpoints and can be enhanced
      by expression of survivin within the nucleus.

PMID- 18829550
TI  - Validation of the p21-activated kinases as targets for inhibition in
      neurofibromatosis type 2.
AB  - Neurofibromatosis type 2 (NF2) is a dominantly inherited cancer disorder caused
      by mutations at the NF2 gene locus. Merlin, the protein product of the NF2 gene,
      has been shown to negatively regulate Rac1 signaling by inhibiting its downstream
      effector kinases, the p21-activated kinases (Pak). Given the implication of Paks
      in tumorigenesis, it is plausible that merlin's tumor suppressive function might
      be mediated, at least in part, via inhibition of the Paks. We present data
      indicating this is indeed the case. First, analysis of primary schwannoma samples
      derived from NF2 patients showed that in a significant fraction of the tumors,
      the activity of Pak1 was highly elevated. Second, we used shRNAs to knockdown
      Pak1, 2, and 3 in NIH3T3 cells expressing a dominant-negative form of merlin,
      NF2(BBA) (NIH3T3/NF2(BBA)), and find that simultaneous knockdown of Pak1-3 in
      these cells significantly reduced their growth rates in vitro and inhibited their
      ability to form tumors in vivo. Finally, while attempting to silence Pak1 in rat
      schwannoma cells, we found that these cells were unable to tolerate long-term
      Pak1 inhibition and rapidly moved to restore Pak1 levels by shutting down Pak1
      shRNA expression through a methylation-dependent mechanism. These data suggest
      that inhibiting Pak could be a beneficial approach for the development of
      therapeutics toward NF2. In addition, the finding that the shRNA-mediated Pak1
      suppression was silenced rapidly by methylation raises questions about the future
      application of such technologies for the treatment of diseases such as cancer.

PMID- 18829551
TI  - The RNA helicase p68 is a novel androgen receptor coactivator involved in
      splicing and is overexpressed in prostate cancer.
AB  - The androgen receptor (AR) is a member of the nuclear steroid hormone receptor
      family and is thought to play an important role in the development of both
      androgen-dependent and androgen-independent prostatic malignancy. Elucidating
      roles by which cofactors regulate AR transcriptional activity may provide
      therapeutic advancement for prostate cancer (PCa). The DEAD box RNA helicase p68
      (Ddx5) was identified as a novel AR-interacting protein by yeast two-hybrid
      screening, and we sought to examine the involvement of p68 in AR signaling and
      PCa. The p68-AR interaction was verified by colocalization of overexpressed
      protein by immunofluorescence and confirmed in vivo by coimmunoprecipitation in
      the PCa LNCaP cell line. Chromatin immunoprecipitation in the same cell line
      showed AR and p68 recruitment to the promoter region of the androgen-responsive
      prostate-specific antigen (PSA) gene. Luciferase reporter, minigene splicing
      assays, and RNA interference (RNAi) were used to examine a functional role of p68
      in AR-regulated gene expression, whereby p68 targeted RNAi reduced AR-regulated
      PSA expression, and p68 enhanced AR-regulated repression of CD44 splicing (P =
      0.008). Tyrosine phosphorylation of p68 was found to enhance coactivation of
      ligand-dependent transcription of AR-regulated luciferase reporters independent
      of ATP-binding. Finally, we observe increased frequency and expression of p68 in
      PCa compared with benign tissue using a comprehensive prostate tissue microarray
      (P = 0.003; P = 0.008). These findings implicate p68 as a novel AR
      transcriptional coactivator that is significantly overexpressed in PCa with a
      possible role in progression to hormone-refractory disease.

PMID- 18829553
TI  - Targeting XIAP bypasses Bcl-2-mediated resistance to TRAIL and cooperates with
      TRAIL to suppress pancreatic cancer growth in vitro and in vivo.
AB  - Resistance to apoptosis is a hallmark of pancreatic cancer, a leading cause of
      cancer deaths. Therefore, novel strategies are required to target apoptosis
      resistance. Here, we report that the combination of X-linked inhibitor of
      apoptosis (XIAP) inhibition and tumor necrosis factor-related apoptosis-inducing
      ligand (TRAIL) is an effective approach to trigger apoptosis despite Bcl-2
      overexpression and to suppress pancreatic cancer growth in vitro and in vivo.
      Knockdown of XIAP by RNA interference cooperates with TRAIL to induce caspase
      activation, loss of mitochondrial membrane potential, cytochrome c release, and
      apoptosis in pancreatic carcinoma cells. Loss of mitochondrial membrane potential
      and cytochrome c release are extensively inhibited by a broad range or caspase-3
      selective caspase inhibitor and by RNAi-mediated silencing of caspase-3,
      indicating that XIAP inhibition enhances TRAIL-induced mitochondrial damage in a
      caspase-3-dependent manner. XIAP inhibition combined with TRAIL even breaks Bcl-2
      imposed resistance by converting type II cells that depend on the mitochondrial
      contribution to the death receptor pathway to type I cells in which TRAIL-induced
      activation of caspase-3 and caspase-9 and apoptosis proceeds irrespective of high
      Bcl-2 levels. Most importantly, XIAP inhibition potentiates TRAIL-induced
      antitumor activity in two preclinical models of pancreatic cancer in vivo. In the
      chicken chorioallantoic membrane model, XIAP inhibition significantly enhances
      TRAIL-mediated apoptosis and suppression of tumor growth. In a tumor regression
      model in xenograft-bearing mice, XIAP inhibition acts in concert with TRAIL to
      cause even regression of established pancreatic carcinoma. Thus, this combination
      of XIAP inhibition plus TRAIL is a promising strategy to overcome apoptosis
      resistance of pancreatic cancer that warrants further investigation.

PMID- 18829552
TI  - ATM and the Mre11-Rad50-Nbs1 complex respond to nucleoside analogue-induced
      stalled replication forks and contribute to drug resistance.
AB  - The Mre11-Rad50-Nbs1 complex and autophosphorylated Ser(1981)-ATM are involved in
      recognizing and repairing DNA damage, such as double-strand breaks (DSB).
      However, the role of these factors in response to stalled replication forks is
      not clear. Nucleoside analogues are agents that are incorporated into DNA during
      replication, which cause stalling of replication forks. The molecular mechanisms
      that sense these events may signal for DNA repair and contribute to survival but
      are poorly understood. Cellular responses to both DSBs and stalled replication
      forks are marked by H2AX phosphorylation on Ser(139) (gamma-H2AX), which forms
      nuclear foci at sites of DNA damage. Here, concentrations of the nucleoside
      analogues 1-beta-d-arabinofuranosylcytosine (cytarabine; ara-C), gemcitabine, and
      troxacitabine, which inhibited DNA synthesis by 90% within 2 hours, were
      determined for each agent. Using gamma-H2AX as a marker for changes in chromatin
      structure, we show that Mre11, Rad50, Nbs1, and phosphorylated ATM respond to
      nucleoside analogue-induced stalled replication forks by forming nuclear foci
      that colocalize with gamma-H2AX within 2 hours. Because neither DSBs nor single
      strand breaks were detectable after nucleoside analogue exposure, we conclude
      that this molecular response is not due to the presence of DNA breaks.
      Deficiencies in ATM, Mre11, or Rad50 led to a 2- to 5-fold increase in clonogenic
      sensitization to gemcitabine, whereas Nbs1 and H2AX deficiency did not affect
      reproductive growth. Taken together, these results suggest that ATM, Mre11, and
      Rad50 are required for survival after replication fork stalling, whereas Nbs1 and
      H2AX are inconsequential.

PMID- 18829554
TI  - Autophagy: a novel mechanism of synergistic cytotoxicity between doxorubicin and
      roscovitine in a sarcoma model.
AB  - Doxorubicin is a genotoxic chemotherapy agent used in treatment of a wide variety
      of cancers. Significant clinical side effects, including cardiac toxicity and
      myelosuppression, severely limit the therapeutic index of this commonly used
      agent and methods which improve doxorubicin efficacy could benefit many patients.
      Because doxorubicin cytotoxicity is cell cycle specific, the cell cycle is a
      rational target to enhance its efficacy. We examined the direct, cyclin-dependent
      kinase inhibitor roscovitine as a means of enhancing doxorubicin cytotoxicity.
      This study showed synergistic cytotoxicity between doxorubicin and roscovitine in
      three sarcoma cell lines: SW-982 (synovial sarcoma), U2OS-LC3-GFP (osteosarcoma),
      and SK-LMS-1 (uterine leiomyosarcoma), but not the fibroblast cell line WI38. The
      combined treatment of doxorubicin and roscovitine was associated with a prolonged
      G(2)-M cell cycle arrest in the three sarcoma cell lines. Using three different
      methods for detecting apoptosis, our results revealed that apoptotic cell death
      did not account for the synergistic cytotoxicity between doxorubicin and
      roscovitine. However, morphologic changes observed by light microscopy and
      increased cytoplasmic LC3-GFP puncta in U20S-LC3-GFP cells after the combined
      treatment suggested the induction of autophagy. Induction of autophagy was also
      shown in SW-982 and SK-LMS-1 cells treated with both doxorubicin and roscovitine
      by acridine orange staining. These results suggest a novel role of autophagy in
      the enhanced cytotoxicity by cell cycle inhibition after genotoxic injury in
      tumor cells. Further investigation of this enhanced cytotoxicity as a treatment
      strategy for sarcomas is warranted.

PMID- 18829555
TI  - RNAi-mediated silencing of nuclear factor erythroid-2-related factor 2 gene
      expression in non-small cell lung cancer inhibits tumor growth and increases
      efficacy of chemotherapy.
AB  - Nuclear factor erythroid-2-related factor 2 (Nrf2) is a redox-sensitive
      transcription factor that regulates the expression of electrophile and xenobiotic
      detoxification enzymes and efflux proteins, which confer cytoprotection against
      oxidative stress and apoptosis in normal cells. Loss of function mutations in the
      Nrf2 inhibitor, Kelch-like ECH-associated protein (Keap1), results in
      constitutive activation of Nrf2 function in non-small cell lung cancer. In this
      study, we show that constitutive activation of Nrf2 in lung cancer cells promotes
      tumorigenicity and contributes to chemoresistance by up-regulation of
      glutathione, thioredoxin, and the drug efflux pathways involved in detoxification
      of electrophiles and broad spectrum of drugs. RNAi-mediated reduction of Nrf2
      expression in lung cancer cells induces generation of reactive oxygen species,
      suppresses tumor growth, and results in increased sensitivity to chemotherapeutic
      drug-induced cell death in vitro and in vivo. Inhibiting Nrf2 expression using
      naked siRNA duplexes in combination with carboplatin significantly inhibits tumor
      growth in a subcutaneous model of lung cancer. Thus, targeting Nrf2 activity in
      lung cancers, particularly those with Keap1 mutations, could be a promising
      strategy to inhibit tumor growth and circumvent chemoresistance.

PMID- 18829556
TI  - Alteration of the mitochondrial apoptotic pathway is key to acquired paclitaxel
      resistance and can be reversed by ABT-737.
AB  - Paclitaxel is a microtubule-targeting antineoplastic drug widely used in human
      cancers. Even when tumors are initially responsive, progression of disease
      despite continued taxane therapy is all too common in the treatment of many of
      the most common epithelial cancers, including breast cancer. However, the
      mechanisms underlying paclitaxel resistance in cancer cells are not completely
      understood. Our hypothesis is that changes in the intrinsic (or mitochondrial)
      cell death pathway controlled by the BCL-2 family are key to the development of
      acquired paclitaxel resistance. Here we show that paclitaxel activates the
      mitochondrial apoptosis pathway, which can be blocked by BCL-2 overexpression.
      Treatment with ABT-737, a small-molecule BCL-2 antagonist, restores sensitivity
      to paclitaxel in BCL-2-overexpressing cells. To investigate the importance of
      changes in the intrinsic apoptotic pathway in the absence of enforced BCL-2
      expression, we generated two independent breast cancer cell lines with acquired
      resistance to apoptosis induced by paclitaxel. In these lines, acquired
      resistance to paclitaxel is mediated either by increased antiapoptotic BCL-2
      proteins or decreased proapoptotic BCL-2 proteins. In both cases, ABT-737 can
      engage the mitochondrial apoptosis pathway to restore sensitivity to paclitaxel
      to cell lines with acquired paclitaxel resistance. In summary, these findings
      suggest that alterations in the intrinsic apoptotic pathway controlled by BCL-2
      protein family members may be crucial to causing paclitaxel resistance.
      Furthermore, our results suggest that combining small-molecule BCL-2 antagonists
      with paclitaxel may offer benefit to patients with paclitaxel-resistant tumors,
      an oncologic problem of great prevalence.

PMID- 18829557
TI  - Optimized clostridium-directed enzyme prodrug therapy improves the antitumor
      activity of the novel DNA cross-linking agent PR-104.
AB  - We have previously shown that spores of the nonpathogenic clostridial strain C.
      sporogenes genetically engineered to express the E. coli-derived cytosine
      deaminase gene are effective in converting systemically injected nontoxic 5
      fluorocytosine into the toxic anticancer drug 5-fluorouracil, thereby producing
      tumor-specific antitumor activity. To improve the expression of E. coli-derived
      genes with this system, we first replaced the original fdP promoter in the vector
      with one of two powerful endogenous clostridial promoters: that of the thiolase
      gene (thlP) and that for the clostridial transcription factor abrB310 (abrBP).
      These substitutions improved protein expression levels of the prodrug-activating
      genes by 2- to 3-fold in comparison with fdP-driven expression. However, despite
      these strong promoters, we found much higher expression of the nitroreductase
      (NTR) protein in the E. coli host compared with the clostridial host, which we
      hypothesized could be the result of different codon use between the two
      organisms. To test this, we constructed new expression vectors with an
      artificially synthesized NTR gene using optimized clostridial codons (sNTR).
      Results from both enzymatic assays and Western blots of cell extracts from
      clostridial transformants harboring plasmid constructs of thlP-sNTR and abrBP
      sNTR showed that the expression and activity of the NTR gene product was
      increased by approximately 20-fold compared with the original construct. In vivo
      studies with i.v. administered sNTR-expressing C. sporogenes spores in SiHa tumor
      bearing mice showed significantly improved antitumor efficacy when combined with
      either 5-aziridinyl-2,4-dinitrobenzamide (CB1954) or the novel dinitrobenzamide
      mustard prodrug, PR-104.

PMID- 18829559
TI  - Evaluation of cancer tests of 1,3-butadiene using internal dose, genotoxic
      potency, and a multiplicative risk model.
AB  - In cancer tests with 1,3-butadiene (BD), the mouse is much more sensitive than
      the rat. This is considered to be related to the metabolism of BD to the epoxide
      metabolites, 1,2-epoxy-3-butene (EB), 1,2:3,4-diepoxybutane, and 1,2-epoxy-3,4
      butanediol. This study evaluates whether the large difference in outcome in
      cancer tests with BD could be predicted quantitatively on the basis of the
      concentration over time in blood (AUC) of the epoxide metabolites, their
      mutagenic potency, and a multiplicative cancer risk model, which has earlier been
      used for ionizing radiation. Published data on hemoglobin adduct levels from
      inhalation experiments with BD were used for the estimation of the AUC of the
      epoxide metabolites in the cancer tests. The estimated AUC of the epoxides were
      then weighed together to a total genotoxic dose, by using the relative genotoxic
      potency of the respective epoxide inferred from in vitro hprt mutation assays
      using EB as standard. The tumor incidences predicted with the risk model on the
      basis of the total genotoxic dose correlated well with the earlier observed tumor
      incidences in the cancer tests. The total genotoxic dose that leads to a doubling
      of the tumor incidences was estimated to be the same in both species, 9 to 10
      mmol/Lxh EB-equivalents. The study validates the applicability of the
      multiplicative cancer risk model to genotoxic chemicals. Furthermore, according
      to this evaluation, different epoxide metabolites are predominating cancer
      initiating agents in the cancer tests with BD, the diepoxide in the mouse, and
      the monoepoxides in the rat.

PMID- 18829558
TI  - Heterogeneity of receptor function in colon carcinoma cells determined by cross
      talk between type I insulin-like growth factor receptor and epidermal growth
      factor receptor.
AB  - This study identifies a novel cross-talk paradigm between the type I insulin-like
      growth factor receptor (IGF1R) and epidermal growth factor receptor (EGFR) in
      colon cancer cells. IGF1R activation by ligand exposure in growth factor-deprived
      cells induces Akt activation in the FET, CBS, and GEO colon cancer cell lines.
      Investigation of IGF1R-mediated signaling pathways using small interfering RNA
      approaches indicated that, as expected, phosphatidylinositol 3'-kinase (PI3K) was
      activated by IGF1R. Mitogen-activated protein kinase (MAPK) activity as reflected
      by phospho-extracellular signal-regulated kinase (ERK) induction was not
      significantly activated until later times following release of these cells from
      growth factor deprivation stress. The appearance of phospho-ERK was proximal to
      EGFR activation. Treatment of cells with the PI3K inhibitor LY294002 before
      release from stress resulted in a concentration-dependent loss of EGFR
      activation, whereas treatment with the MAPK inhibitor PD98059 did not block EGFR
      activation, indicating that EGFR activation was downstream of the IGF1R/PI3K
      pathway. PD98059 inhibition of MAPK was associated with a concentration-dependent
      reduction in EGFR-mediated phospho-ERK. EGFR inhibitor blocked induction of
      phospho-ERK, showing that MAPK activity was a consequence of EGFR-mediated
      signaling. On the other hand, a small-molecule IGF1R inhibitor, PQIP, blocked Akt
      phosphorylation. The divergent signaling functions of IGF1R and EGFR suggested
      the potential for synergism by a combination of therapy directed at the two
      receptors. Combination treatment with PQIP and EGFR inhibitor Tarceva resulted in
      synergistic effects as indicated by combination index analysis in all three cell
      lines tested.

PMID- 18829560
TI  - NVP-BEZ235, a dual PI3K/mTOR inhibitor, prevents PI3K signaling and inhibits the
      growth of cancer cells with activating PI3K mutations.
AB  - Phosphatidylinositol-3-kinase (PI3K) pathway deregulation is a common event in
      human cancer, either through inactivation of the tumor suppressor phosphatase and
      tensin homologue deleted from chromosome 10 or activating mutations of p110
      alpha. These hotspot mutations result in oncogenic activity of the enzyme and
      contribute to therapeutic resistance to the anti-HER2 antibody trastuzumab. The
      PI3K pathway is, therefore, an attractive target for cancer therapy. We have
      studied NVP-BEZ235, a dual inhibitor of the PI3K and the downstream mammalian
      target of rapamycin (mTOR). NVP-BEZ235 inhibited the activation of the downstream
      effectors Akt, S6 ribosomal protein, and 4EBP1 in breast cancer cells. The
      antiproliferative activity of NVP-BEZ235 was superior to the allosteric selective
      mTOR complex inhibitor everolimus in a panel of 21 cancer cell lines of different
      origin and mutation status. The described Akt activation due to mTOR inhibition
      was prevented by higher doses of NVP-BEZ235. NVP-BEZ235 reversed the
      hyperactivation of the PI3K/mTOR pathway caused by the oncogenic mutations of
      p110-alpha, E545K, and H1047R, and inhibited the proliferation of HER2-amplified
      BT474 cells exogenously expressing these mutations that render them resistant to
      trastuzumab. In trastuzumab-resistant BT474 H1047R breast cancer xenografts, NVP
      BEZ235 inhibited PI3K signaling and had potent antitumor activity. In treated
      animals, there was complete inhibition of PI3K signaling in the skin at
      pharmacologically active doses, suggesting that skin may serve as surrogate
      tissue for pharmacodynamic studies. In summary, NVP-BEZ235 inhibits the PI3K/mTOR
      axis and results in antiproliferative and antitumoral activity in cancer cells
      with both wild-type and mutated p110-alpha.

PMID- 18829561
TI  - Vitamin C antagonizes the cytotoxic effects of antineoplastic drugs.
AB  - Vitamin C is an antioxidant vitamin that has been hypothesized to antagonize the
      effects of reactive oxygen species-generating antineoplastic drugs. The
      therapeutic efficacy of the widely used antineoplastic drugs doxorubicin,
      cisplatin, vincristine, methotrexate, and imatinib were compared in leukemia
      (K562) and lymphoma (RL) cell lines with and without pretreatment with
      dehydroascorbic acid, the commonly transported form of vitamin C. The effect of
      vitamin C on viability, clonogenicity, apoptosis, P-glycoprotein, reactive oxygen
      species (ROS), and mitochondrial membrane potential was determined. Pretreatment
      with vitamin C caused a dose-dependent attenuation of cytotoxicity, as measured
      by trypan blue exclusion and colony formation after treatment with all
      antineoplastic agents tested. Vitamin C given before doxorubicin treatment led to
      a substantial reduction of therapeutic efficacy in mice with RL cell-derived
      xenogeneic tumors. Vitamin C treatment led to a dose-dependent decrease in
      apoptosis in cells treated with the antineoplastic agents that was not due to up
      regulation of P-glycoprotein or vitamin C retention modulated by antineoplastics.
      Vitamin C had only modest effects on intracellular ROS and a more general
      cytoprotective profile than N-acetylcysteine, suggesting a mechanism of action
      that is not mediated by ROS. All antineoplastic agents tested caused
      mitochondrial membrane depolarization that was inhibited by vitamin C. These
      findings indicate that vitamin C given before mechanistically dissimilar
      antineoplastic agents antagonizes therapeutic efficacy in a model of human
      hematopoietic cancers by preserving mitochondrial membrane potential. These
      results support the hypothesis that vitamin C supplementation during cancer
      treatment may detrimentally affect therapeutic response.

PMID- 18829563
TI  - Potent in vitro and in vivo activity of an Fc-engineered anti-CD19 monoclonal
      antibody against lymphoma and leukemia.
AB  - CD19 is a pan B-cell surface receptor expressed from pro-B-cell development until
      its down-regulation during terminal differentiation into plasma cells. CD19
      represents an attractive immunotherapy target for cancers of lymphoid origin due
      to its high expression levels on the vast majority of non-Hodgkin's lymphomas and
      some leukemias. A humanized anti-CD19 antibody with an engineered Fc domain
      (XmAb5574) was generated to increase binding to Fcgamma receptors on immune cells
      and thus increase Fc-mediated effector functions. In vitro, XmAb5574 enhanced
      antibody-dependent cell-mediated cytotoxicity 100-fold to 1,000-fold relative to
      an anti-CD19 IgG1 analogue against a broad range of B-lymphoma and leukemia cell
      lines. Furthermore, XmAb5574 conferred antibody-dependent cell-mediated
      cytotoxicity against patient-derived acute lymphoblastic leukemia and mantle cell
      lymphoma cells, whereas the IgG1 analogue was inactive. XmAb5574 also increased
      antibody-dependent cellular phagocytosis and apoptosis. In vivo, XmAb5574
      significantly inhibited lymphoma growth in prophylactic and established mouse
      xenograft models, and showed more potent antitumor activity than its IgG1
      analogue. Comparisons with a variant incapable of Fcgamma receptor binding showed
      that engagement of these receptors is critical for optimal antitumor efficacy.
      These results suggest that XmAb5574 exhibits potent tumor cytotoxicity via direct
      and indirect effector functions and thus warrants clinical evaluation as an
      immunotherapeutic for CD19(+) hematologic malignancies.

PMID- 18829562
TI  - Addiction to elevated insulin-like growth factor I receptor and initial
      modulation of the AKT pathway define the responsiveness of rhabdomyosarcoma to
      the targeting antibody.
AB  - Insulin-like growth factor I receptor (IGF-IR) and its ligands are overexpressed
      by tumors, mediating proliferation and protecting against stress-induced
      apoptosis. Accordingly, there has been a considerable amount of interest in
      developing therapeutic agents against IGF-IR. IGF-IR is believed to be
      ubiquitously expressed without detectable mutation or amplification in cancer. We
      explored the determinants of cellular response to a humanized anti-IGF-IR
      antibody. Our results showed a large variation in IGF-IR levels in
      rhabdomyosarcoma tumor specimens that were comparable with those in
      rhabdomyosarcoma cell lines. In vitro analysis revealed a direct and very
      significant correlation between elevated IGF-IR levels and antiproliferative
      effects of the antibody and defined a receptor number that would predict
      sensitivity. Our data further suggested a strong dependence on IGF-IR for AKT
      signaling in cells with elevated IGF-IR. The sensitivity of the high IGF-IR
      expressing cells was blocked with a constitutively active AKT. The extracellular
      signal-regulated kinase pathway was not affected by the antibody. In vivo studies
      showed that anti-IGF-IR had single-agent antitumor activity; furthermore,
      predictions of responses based on IGF-IR levels were accurate. In vivo biomarker
      analysis suggested that h7C10 down-regulated both IGF-IR and p-AKT initially,
      concordant with antitumor activity. Subsequent progression of tumors was
      associated with reactivation of p-AKT despite sustained suppression of IGF-IR.
      These results identified the first predictive biomarker for anti-IGF-IR therapies
      in cancer.

PMID- 18829564
TI  - Development of cellular immune responses against PAX5, a novel target for cancer
      immunotherapy.
AB  - PAX5 is a member of the PAX family of developmental transcription factors with an
      important role in B-cell development. Its expression in normal adult tissue is
      limited to the hemopoietic system, but it is aberrantly expressed in a number of
      solid cancers and leukemias where it functions as an oncogene. We therefore
      hypothesized that anti-PAX5 immune responses could be used to target a number of
      malignancies without significant toxicity. We screened PAX5 peptides for the
      ability to bind HLA-A2 and identified a novel sequence, TLPGYPPHV (referred to as
      TLP). CTL lines against TLP were generated from peripheral blood of five normal
      HLA-A2-positive blood donors and showed specific HLA-A2-restricted killing
      against PAX5-expressing target cells. We generated high-avidity CTL clones from
      these lines capable of killing cells pulsed with <1 nmol/L of TLP and killing a
      range of PAX5-expressing malignant cell lines. I.v. injection of an anti-PAX5 CTL
      clone into immunodeficient mice bearing s.c. human tumors resulted in specific
      growth inhibition of PAX5-expressing tumors. This knowledge can be used for the
      therapeutic generation of CTL lines or the cloning of high-avidity T-cell
      receptor genes for use in adoptive immunotherapy.

PMID- 18829565
TI  - Cancer immunotherapy targeting the high molecular weight melanoma-associated
      antigen protein results in a broad antitumor response and reduction of pericytes
      in the tumor vasculature.
AB  - The high molecular weight melanoma-associated antigen (HMW-MAA), also known as
      melanoma chondroitin sulfate proteoglycan, has been used as a target for the
      immunotherapy of melanoma. This antigen is expressed on the cell surface and has
      a restricted distribution in normal tissues. Besides its expression in a broad
      range of transformed cells, this antigen is also found in pericytes, which are
      important for tumor angiogenesis. We generated a recombinant Listeria
      monocytogenes (Lm-LLO-HMW-MAA-C) that expresses and secretes a fragment of HMW
      MAA (residues 2,160-2,258) fused to the first 441 residues of the listeriolysin O
      (LLO) protein. Immunization with Lm-LLO-HMW-MAA-C was able to impede the tumor
      growth of early established B16F10-HMW-MAA tumors in mice and both CD4(+) and
      CD8(+) T cells were required for therapeutic efficacy. Immune responses to a
      known HLA-A2 epitope present in the HMW-MAA(2160-2258) fragment was detected in
      the HLA-A2/K(b) transgenic mice immunized with Lm-LLO-HMW-MAA-C. Surprisingly,
      this vaccine also significantly impaired the in vivo growth of other tumorigenic
      cell lines, such as melanoma, renal carcinoma, and breast tumors, which were not
      engineered to express HMW-MAA. One hypothesis is that the vaccine could be
      targeting pericytes, which are important for tumor angiogenesis. In a breast
      tumor model, immunization with Lm-LLO-HMW-MAA-C caused CD8(+) T-cell infiltration
      in the tumor stroma and a significant decrease in the number of pericytes in the
      tumor blood vessels. In conclusion, a Lm-based vaccine against HMW-MAA can
      trigger cell-mediated immune responses to this antigen that can target not only
      tumor cells but also pericytes in the tumor vasculature.

PMID- 18829566
TI  - CD8+ T-cell responses against hemoglobin-beta prevent solid tumor growth.
AB  - Bone marrow-derived dendritic cells engineered using recombinant adenovirus to
      secrete high levels of IL-12p70 dramatically inhibited the growth of established
      CMS4 sarcomas in BALB/c mice after intratumoral administration. An analysis of
      splenic CD8(+) T cells in regressor mice revealed a strong, complex reactivity
      pattern against high-performance liquid chromatography (HPLC)-resolved peptides
      isolated by acid elution from single-cell suspensions of surgically resected CMS4
      lesions. Mass spectrometry analyses defined two major overlapping peptide species
      that derive from the murine hemoglobin-beta (HBB) protein within the most
      stimulatory HPLC fractions. Although cultured CMS4 tumor cells failed to express
      HBB mRNA based on reverse transcription-PCR analyses, prophylactic vaccination of
      BALB/c mice with vaccines containing HBB peptides promoted specific CD8(+) T-cell
      responses that protected mice against a subsequent challenge with CMS4 or
      unrelated syngeneic (HBB(neg)) tumors of divergent histology (sarcoma, carcinomas
      of the breast or colon). In situ imaging suggested that vaccines limit or
      destabilize tumor-associated vascular structures, potentially by promoting
      immunity against HBB+ vascular pericytes. Importantly, there were no untoward
      effects of vaccination with the HBB peptide on peripheral RBC numbers, RBC
      hemoglobin content, or vascular structures in the brain or eye.

PMID- 18829567
TI  - Presentation of telomerase reverse transcriptase, a self-tumor antigen, is down
      regulated by histone deacetylase inhibition.
AB  - Histone deacetylases (HDAC) modify the architecture of chromatin, leading to
      decreased gene expression, an effect that is reversed by HDAC inhibition. The
      balance between deacetylation and acetylation is central to many biological
      events including the regulation of cell proliferation and cancer but also the
      differentiation of immune T cells. The effects of HDAC inhibition on the
      interaction between antitumor effector T cells and tumor cells are not known.
      Here, we studied presentation of a universal self-tumor antigen, telomerase
      reverse transcriptase, in human tumor cells during HDAC inhibition. We found that
      HDAC inhibition with trichostatin A was associated with a decreased presentation
      and diminished killing of tumor cells by CTLs. Using gene array analysis, we
      found that HDAC inhibition resulted in a decrease of genes coding for proteasome
      catalytic proteins and for tapasin, an endoplasmic reticulum resident protein
      involved in the MHC class I pathway of endogenous antigen presentation. Our
      findings indicate that epigenetic changes in tumor cells decrease self-tumor
      antigen presentation and contribute to reduced recognition and killing of tumor
      cells by cytotoxic T lymphocytes. This mechanism could contribute to tumor escape
      from immune surveillance.

PMID- 18829569
TI  - The melanoma-associated antigen A3 mediates fibronectin-controlled cancer
      progression and metastasis.
AB  - Tumor cells frequently exhibit decreased adhesiveness due to failure to deposit
      stromal fibronectin (FN), permitting more rapid proliferation, migration,
      invasion, and metastasis. Although up-regulation of FN has been noted in gene
      profiles of carcinomas compared with normal tissue, reduced FN expression has
      been described at the peripheral margins of invading tumors. In this study, we
      investigate the role of FN in cancer behavior. Using human thyroid carcinoma
      cells with stably down-regulated FN, we performed gene profiling and created an
      orthotopic mouse model. We stably overexpressed the FN target, MAGE A3, which has
      also been identified as a target of the breast cancer risk factor fibroblast
      growth factor receptor 2, and examined the functional effects in vitro and in
      vivo in a flank model and an orthotopic model of thyroid cancer. Mouse xenografts
      showed significantly enhanced tumor growth as well as larger and more numerous
      lung metastases in response to FN silencing. Gene profiling identified the
      melanoma-associated antigen (MAGE A3) as significantly up-regulated in response
      to FN silencing. Forced expression of MAGE A3 resulted in p21 down-regulation,
      accelerated cell cycle progression, increased cell migration rate, and invasion
      in vitro and in vivo in an orthotopic mouse model where microcomputed tomography
      confirmed lung metastases that recapitulate the progression of human thyroid
      cancer. We conclude that MAGE A3 is a functional integrator of diverse signals,
      including FGFR2 and FN, to modulate cancer progression.

PMID- 18829568
TI  - Abnormal DNA methylation of CD133 in colorectal and glioblastoma tumors.
AB  - Much recent effort has focused on identifying and characterizing cellular markers
      that distinguish tumor propagating cells (TPC) from more differentiated progeny.
      We report here an unusual promoter DNA methylation pattern for one such marker,
      the cell surface antigen CD133 (Prominin 1). This protein has been extensively
      used to enrich putative cancer propagating stem-like cell populations in
      epithelial tumors and, especially, glioblastomas. We find that, within individual
      cell lines of cultured colon cancers and glioblastomas, the promoter CpG island
      of CD133 is DNA methylated, primarily, in cells with absent or low expression of
      the marker protein, whereas lack of such methylation is evident in purely CD133+
      cells. Differential histone modification marks of active versus repressed genes
      accompany these DNA methylation changes. This heterogeneous CpG island DNA
      methylation status in the tumors is unusual in that other DNA hypermethylated
      genes tested in such cultures preserve their methylation patterns between
      separated CD133+ and CD133- cell populations. Furthermore, the CD133 DNA
      methylation seems to constitute an abnormal promoter signature because it is not
      found in normal brain and colon but only in cultured and primary tumors. Thus,
      the DNA methylation is imposed on the transition between the active versus
      repressed transcription state for CD133 only in tumors. Our findings provide
      additional insight for the dynamics of aberrant DNA methylation associated with
      aberrant gene silencing in human tumors.

PMID- 18829570
TI  - A bicistronic CYCLIN D1-TROP2 mRNA chimera demonstrates a novel oncogenic
      mechanism in human cancer.
AB  - A chimeric CYCLIN D1-TROP2 mRNA was isolated from human ovarian and mammary
      cancer cells. The CYCLIN D1-TROP2 mRNA was shown to be a potent oncogene as it
      transforms naive, primary cells in vitro and induces aggressive tumor growth in
      vivo in cooperation with activated RAS. Silencing of the chimeric mRNA inhibits
      the growth of breast cancer cells. The CYCLIN D1-TROP2 mRNA was expressed by a
      large fraction of the human gastrointestinal, ovarian, and endometrial tumors
      analyzed. It is most frequently detected in intestinal cell aneuploid cancers and
      it is coexpressed with activated RAS oncogenes, consistent with a cooperative
      transforming activity in human cancers. The chimeric mRNA is a bicistronic
      transcript of post transcriptional origin that independently translates the
      Cyclin D1 and Trop-2 proteins. This is a novel mechanism of CYCLIN D1 activation
      that achieves the truncation of the CYCLIN D1 mRNA in the absence of chromosomal
      rearrangements. This leads to a higher CYCLIN D1 mRNA stability, with
      inappropriate expression during the cell cycle. The stabilized CYCLIN D1 mRNA
      cooperates with TROP2 in stimulating the growth of the expressing cells. These
      findings show a novel epigenetic, oncogenic mechanism, which seems to be
      widespread in human cancers.

PMID- 18829571
TI  - Chromosomal instability in unirradiated hemaopoietic cells induced by macrophages
      exposed in vivo to ionizing radiation.
AB  - The tumorigenic potential of ionizing radiation has conventionally been
      attributed to DNA damage in irradiated cells induced at the time of exposure.
      Recently, there have been an increasing number of reports of damage in
      unirradiated cells that are either neighbors or descendants of irradiated cells,
      respectively, regarded as bystander effects and genomic instability and
      collectively termed nontargeted effects. In this study, we show that descendants
      of normal murine hemaopoietic clonogenic stem cells exposed to bone marrow
      conditioned medium derived from gamma-irradiated mice exhibit chromosomal
      instability unlike the descendants of directly gamma-irradiated cells. The
      instability is expressed in bone marrow cells of the radiation-induced acute
      myeloid leukemia (r-AML) susceptible strain (CBA/Ca) but not in mice resistant to
      r-AML (C57BL/6). Furthermore, crossgenetic experiments show the induction of the
      instability phenotype requires both the producer and responder cells to be of the
      susceptible CBA/Ca genotype. Macrophages are the source of the bystander signals,
      and the signaling mechanism involves tumor necrosis factor-alpha, nitric oxide,
      and superoxide. The findings show a genotype-dependent chromosomal instability
      phenotype induced by radiation-induced macrophage-mediated bystander signaling.
      As the majority of accidental, occupational, and therapeutic exposures to
      ionizing radiation are partial body exposures, the findings have implications for
      understanding the consequences of such exposure.

PMID- 18829572
TI  - PIK3CA cooperates with other phosphatidylinositol 3'-kinase pathway mutations to
      effect oncogenic transformation.
AB  - Mutations in genes functioning in different pathways frequently occur together in
      the same cancer, whereas mutations in the same pathway tend to be mutually
      exclusive. However, the majority of colon, breast, and endometrial cancers that
      possess mutations in PIK3CA, the catalytic subunit p110alpha of
      phosphatidylinositol 3'-kinase (PI3K), also possess mutations or alterations in
      genes upstream of PI3K such as Ras, ERBB2/ERBB3, or PTEN. PIK3CA mutations occur
      almost exclusively in invasive tumors, whereas upstream mutations occur as
      frequently in early-stage and late-stage tumors, suggesting that PIK3CA mutation
      is a late-stage event that may augment earlier activation of the PI3K pathway.
      Consistent with this, we find that levels of p-AKT (Ser(473)) induced by mutant
      Ras or knockdown of PTEN were dramatically increased by addition of mutant
      PIK3CA. Soft agar assays revealed that anchorage-independent growth induced by
      mutant Ras was greatly increased in the presence of mutant PIK3CA. In breast,
      colon, and endometrial cancers in which the PI3K pathway is activated by a
      combination of mutant PIK3CA and alterations in Ras, ERBB2/3, or PTEN, signaling
      to downstream elements such as Akt was mediated exclusively by the p110alpha
      isoform, rather than a combination of different PI3K isoforms. Our data therefore
      suggest that in tumors with co-occurring mutations in multiple components of the
      PI3K pathway, selective inhibition of the alpha isoform of p110 is an attractive
      therapeutic strategy, especially for late-stage tumors.

PMID- 18829573
TI  - Functional analysis of a cell cycle-associated, tumor-suppressive gene, protein
      tyrosine phosphatase receptor type G, in nasopharyngeal carcinoma.
AB  - Functional studies to identify the potential role of a chromosome 3p14-21 gene,
      protein tyrosine phosphatase receptor type G (PTPRG), were performed. PTPRG was
      identified as a candidate tumor suppressor gene (TSG) in nasopharyngeal carcinoma
      (NPC) by differential gene profiling of tumorigenic and nontumorigenic NPC
      chromosome 3 microcell hybrids (MCH). Down-regulation of this gene was found in
      tumor segregants when compared with their corresponding tumor-suppressive MCHs,
      as well as in NPC cell lines and tumor biopsies. Promoter hypermethylation and
      loss of heterozygosity were found to be important mechanisms contributing to
      PTPRG silencing. PTPRG overexpression in NPC cell lines induces growth
      suppression and reduced anchorage-independent growth in vitro. This is the first
      study to use a tetracycline-responsive vector expression system to study PTPRG
      stable transfectants. Results indicate its ability to induce significant tumor
      growth suppression in nude mice under conditions activating transgene expression.
      These studies now provide functional evidence indicating critical interactions of
      PTPRG in the extracellular matrix milieu induce cell arrest and changes in cell
      cycle status. This is associated with inhibition of pRB phosphorylation through
      down-regulation of cyclin D1. These novel findings enhance our current
      understanding of how PTPRG may contribute to tumorigenesis.

PMID- 18829574
TI  - Pericentromeric instability and spontaneous emergence of human neoacrocentric and
      minute chromosomes in the alternative pathway of telomere lengthening.
AB  - In the alternative pathway of telomere lengthening (ALT), neoplastic cell growth
      is prolonged by telomere recombination. We show that ALT is unexpectedly
      characterized by high rates of ongoing pericentromeric chromosomal instability.
      Combined with telomeric recombination, ALT pericentromeric instability generates
      neoacrocentric chromosomes. In the present studies, we describe a subgroup of ALT
      neoacrocentric minute chromosomes, composed of DNA entities two to five times
      smaller in size than human chromosome 21. The frequencies of ALT minute
      chromosomes were increased by gamma-irradiation and suppressed by telomerase.
      Continuous growth after telomerase inhibition/depletion was followed by increased
      rates of telomeric sister chromatid recombination and the emergence of minute
      chromosomes. We show that ALT minute chromosomes were derived from true
      centromeric fissions and/or chromosomal breakage/fusion/bridge cycles. They
      exhibit a two-chromatid structure, carry genomic DNA, centromeric and telomeric
      repeats, and display regular mitotic functionality. These observations are
      important in understanding the global genomic instability that characterizes most
      human advanced malignancies.

PMID- 18829575
TI  - Maintenance of constitutive IkappaB kinase activity by glycogen synthase kinase
      3alpha/beta in pancreatic cancer.
AB  - Constitutive nuclear factor kappaB (NF-kappaB) activation is among the many
      deregulated signaling pathways that are proposed to drive pancreatic cancer cell
      growth and survival. Recent reports suggest that glycogen synthase kinase-3beta
      (GSK-3beta) plays a key role in maintaining basal NF-kappaB target gene
      expression and cell survival in pancreatic cancer cell lines. However, the
      mechanism by which GSK-3beta facilitates constitutive NF-kappaB signaling in
      pancreatic cancer remains unclear. In this report, we analyze the contributions
      of both GSK-3 isoforms (GSK-3alpha and GSK-3beta) in regulating NF-kappaB
      activation and cell proliferation in pancreatic cancer cell lines (Panc-1 and
      MiaPaCa-2). We show that GSK-3 isoforms are differentially required to maintain
      basal NF-kappaB DNA binding activity, transcriptional activity, and cell
      proliferation in Panc-1 and MiaPaCa-2 cells. Our data also indicate that IkappaB
      kinase (IKK) subunits are not equally required to regulate pancreatic cancer
      associated NF-kappaB activity and cell growth. Importantly, we provide the first
      evidence that GSK-3 maintains constitutive NF-kappaB signaling in pancreatic
      cancer by regulating IKK activity. These data provide new insight into GSK-3
      dependent NF-kappaB regulation and further establish GSK-3 and IKK as potential
      therapeutic targets for pancreatic cancer.

PMID- 18829576
TI  - MicroRNA-21 targets a network of key tumor-suppressive pathways in glioblastoma
      cells.
AB  - MicroRNA dysregulation is observed in different types of cancer. MiR-21 up
      regulation has been reported for the majority of cancers profiled to date;
      however, knowledge is limited on the mechanism of action of miR-21, including
      identification of functionally important targets that contribute to its
      proproliferative and antiapoptotic actions. In this study, we show for the first
      time that miR-21 targets multiple important components of the p53, transforming
      growth factor-beta (TGF-beta), and mitochondrial apoptosis tumor-suppressive
      pathways. Down-regulation of miR-21 in glioblastoma cells leads to derepression
      of these pathways, causing repression of growth, increased apoptosis, and cell
      cycle arrest. These phenotypes are dependent on two of the miR-21 targets
      validated in this study, HNRPK and TAp63. These findings establish miR-21 as an
      important oncogene that targets a network of p53, TGF-beta, and mitochondrial
      apoptosis tumor suppressor genes in glioblastoma cells.

PMID- 18829577
TI  - Androgenic control of transforming growth factor-beta signaling in prostate
      epithelial cells through transcriptional suppression of transforming growth
      factor-beta receptor II.
AB  - The androgen receptor cross-talks with transforming growth factor-beta (TGF-beta)
      through mechanisms that remain poorly understood. Here we provide strong evidence
      that 5alpha-dihydrotestosterone (DHT) intercepts the ability of prostate
      epithelial cells to undergo TGF-beta-induced apoptosis, and present a new model
      for this androgenic effect. We report that DHT decreases the level of TGF-beta
      receptor II (TbetaRII) through a transcriptional mechanism, leading to
      suppression of the ability of TGF-beta to down-regulate expression of Bcl-xL and
      cyclin Ds, activate caspase-3, and induce apoptosis. Promoter analysis, DNA
      pulldown, and electrophoretic mobility shift assays support that transcriptional
      down-regulation of TbetaRII by DHT occurs through Sp1/Sp3 response elements, with
      the binding of Sp1 to the TbetaRII promoter being suppressed by DHT, largely
      driven by loss of Sp1 protein and/or activity. These results provide fresh
      insight on the mechanism of growth control by androgens and the progression of
      prostate cancer to androgen independence. [Cancer Res 2008;68(19):8173-82].

PMID- 18829578
TI  - Endothelial p70 S6 kinase 1 in regulating tumor angiogenesis.
AB  - The p70 S6 kinase 1 (p70S6K1) exerts its function in regulating protein
      synthesis, cell proliferation, cell cycle progression, and cell survival in
      response to growth factors and other cellular signals. But the direct effect of
      p70S6K1 in regulating tumor growth and angiogenesis remains to be elucidated.
      Here, we investigated the effect of p70S6K1 expressed in human dermal
      microvascular endothelial cells (HDMEC) in regulating cancer cell-inducing tumor
      growth and angiogenesis and found that HDMECs enhance cancer cell-induced tumor
      growth and angiogenesis. Constitutive activation of p70S6K1 in HDMECs is
      sufficient to enhance tumor growth and angiogenesis. Inhibition of p70S6K1 by its
      dominant-negative mutant in HDMECs interferes with tumor growth and angiogenesis,
      indicating that p70S6K1 activity in endothelial cells is required for regulating
      tumor angiogenesis. We found that p70S6K1 regulates hypoxia-inducible factor
      1alpha (HIF-1alpha) expression in the human endothelial cells. Knockdown of HIF
      1alpha in the endothelial cells decreases tumor growth and angiogenesis. These
      results show that p70S6K1 and HIF-1 play an important role in regulating the
      endothelial functions for inducing tumor growth and angiogenesis. This study
      helps to understand the role and molecular mechanism of p70S6K1 in regulating
      angiogenesis and tumor growth, and the role of endothelial p70S6K1/HIF-1
      signaling in the regulation of tumor microenvironment and angiogenesis.

PMID- 18829579
TI  - Does clinical education need a series of tools to assess success?

PMID- 18829580
TI  - Invited commentary.

PMID- 18829581
TI  - Invited commentary.

PMID- 18829582
TI  - On "Puckering and blowing facial expressions..." Denlinger RL, et al. Phys Ther.
      2008;88:909-915.

PMID- 18829583
TI  - Midterm follow-up after pharmacomechanical thrombolysis for lower extremity deep
      venous thrombosis.
AB  - OBJECTIVE: To provide follow-up in patients treated with pharmacomechanical
      thrombolysis (PhMT) for lower extremity deep venous thrombosis (DVT). METHODS:
      Retrospective analysis of prospectively collected data. Patients underwent
      clinical evaluation, duplex ultrasound, venous clinical severity scoring, venous
      segmental disease scoring, and venous disability scoring. RESULTS: Fourteen
      patients were available for evaluation. Median age was 40 years (19-58). Median
      follow-up was 24 months (13-69 months). Thirteen of 14 patients (93%) had a
      venous disability score < 1 and 13 of 14 patients (93%) had a venous clinical
      severity scoring < 5. In all but 1 patient the venous segmental disease scoring
      score was < 5. All iliac segments were patent, all but 3 patients had partial
      infrainguinal obstruction and 5 of 14 (36%) had reflux. CONCLUSIONS: Our data
      demonstrate that the good early clinical results after PhMT can be sustained on
      longer follow-up and may prevent the development of advanced postthrombotic
      syndrome.

PMID- 18829584
TI  - Retrograde stent-graft angioplasty of superficial femoral artery occlusion in a
      claudicant.
AB  - Endovascular therapy has become an accepted mode of therapy for lifestyle
      limiting claudication, especially if the disease is confined to the superficial
      femoral artery (SFA). The standard approach to these lesions is from the
      contralateral femoral artery and crossing over the aortic bifurcation. In
      patients who have an aortobifemoral bypass (AFB), this technique is usually not
      feasible secondary to the angles of the graft. The authors report on their
      approach to a 60-year-old man with lifestyle-limiting claudication and SFA
      disease, and an AFB in place. They performed a retrograde approach to the SFA via
      a small above-knee popliteal artery exposure. They used the recently approved (in
      the United States) heparin-bonded VIABAHN for the revascularization via this
      approach, which would have allowed them to proceed to an open bypass procedure if
      they were unsuccessful in the same setting.

PMID- 18829585
TI  - Adult-onset dysphagia lusoria from an uncommon vascular ring: a case report and
      review of the literature.
AB  - Vascular rings are a rare cause of symptoms in adult patients. We report the case
      of a 48-year-old woman presenting with dysphagia lusoria due to an uncommon
      vascular ring: right aortic arch with mirror-image branching and a left
      ligamentum arteriosum. No previous reports exist of adult-onset dysphagia lusoria
      attributable to this anatomy. The patient underwent a limited muscle-sparing
      thoracotomy with division of the ligamentum. The division interrupted the
      vascular ring and relieved her esophageal compression. The presentation,
      evaluation, pathophysiology, and treatment of this condition are discussed.

PMID- 18829586
TI  - Risk factors for surgical-site infection following common femoral artery
      endarterectomy.
AB  - Surgical-site infection is a major complication following endarterectomy of the
      common femoral artery. The aim of this single-center study was to determine risk
      factors for surgical-site infection after endarterectomy of the common femoral
      artery and especially the possible association between patch type (venous,
      bovine, or prosthetic) and the occurrence of groin infection. Retrospectively 140
      patients who underwent an endarterectomy of the common femoral artery between
      2003 and 2006 were reviewed. About 20 patients (14%) suffered from a surgical
      site infection (12 superficial and 8 deep, of which 2 with involvement of the
      patch). All infections occurred within 30 days postoperatively. There was no
      statistically significant difference between type of patch and surgical-site
      infection. However, using multivariate analysis, previous arterial surgery in the
      groin (P = .013) and a wound drain left postoperatively (P = .016) were
      independent variables for the development of a surgical-site infection after
      endarterectomy of the common femoral artery.

PMID- 18829587
TI  - Effect of pollination on floral longevity and costs of delaying fertilization in
      the out-crossing Polygala vayredae Costa (Polygalaceae).
AB  - BACKGROUND AND AIMS: The effect of pollination on flower life span has been
      widely studied, but so far little attention has been paid to the reproductive
      consequences of delayed pollination in plants with long floral life spans. In the
      present study, Polygala vayredae was used to answer the following questions. (1)
      How does male and female success affect the floral longevity of individual
      flowers? (2) How does delaying fertilization affect the female fitness of this
      species? METHODS: Floral longevity was studied after experimental pollinations
      involving male and/or female accomplishment, bagging and open pollination. The
      reproductive costs of a delay in the moment of fertilization were evaluated
      through fruit set, seed-ovule ratio and seed weight, after pollination of flowers
      that had been bagged for 2-18 d. KEY RESULTS: Senescence of the flowers of P.
      vayredae was activated by pollen reception on the stigmatic papillae, while
      pollen removal had no effect on floral longevity. Nonetheless, a minimum
      longevity of 8 d was detected, even after successful pollination and pollen
      dissemination. This period may be involved with the enhancement of male accrual
      rates, as the female accomplishment is generally achieved after the first visit.
      Floral life span of open-pollinated flowers was variable and negatively
      correlated with pollinator visitation rates. Delayed pollination had a major
      impact on the reproductive success of the plant, with fruit set, seed-ovule ratio
      and seed weight being significantly diminished with the increase of flower age at
      the moment of fertilization. CONCLUSIONS: A strong relationship between
      pollination and floral longevity was observed. Flowers revealed the ability to
      extend or reduce their longevity, within some limits, in response to the
      abundance of efficient pollinators (i.e. reproductive fulfilment rates).
      Furthermore, with scarce or unpredictable pollinators, a long floral life span
      could maintain the opportunity for fertilization but would also have reproductive
      costs on production of offspring. Reduced female fitness late in the flower's
      life could shift the cost-benefit balance towards a shorter life span, partially
      counteracting the selection for longer floral life span potentially mediated by
      scarce pollination services.

PMID- 18829588
TI  - Two cap-binding proteins CBP20 and CBP80 are involved in processing primary
      MicroRNAs.
AB  - MicroRNAs (miRNAs) are 21 nt RNAs that regulate many biological processes in
      plants by mediating translational inhibition or cleavage of target transcripts.
      Arabidopsis mutants defective in miRNA biogenesis have overlapping and highly
      pleiotropic phenotypes including serrated leaves and ABA hypersensitivity. Recent
      evidence indicates that miRNA genes are transcribed by RNA polymerase II (Pol
      II). Since Pol II transcripts are capped, we hypothesized that CBP (cap-binding
      protein) 20 and 80 may bind to capped primary miRNA (pri-miRNA) transcripts and
      play a role in their processing. Here, we show that cbp20 and cbp80 mutants have
      reduced miRNA levels and increased pri-miRNA levels. Co-immunoprecipitation
      experiments revealed that pri-miRNAs 159, 166, 168 and 172 could be associated
      with CBP20 and CBP80. We found that CBP20 and CBP80 are stabilized by ABA by a
      post-translational mechanism, and these proteins are needed for ABA induction of
      miR159 during seed germination. The lack of miR159 accumulation in ABA-treated
      seeds of cbp20/80 mutants leads to increased MYB33 and MYB101 transcript levels,
      and presumably higher levels of these positive regulators result in ABA
      hypersensitivity. Genetic and molecular analyses show that CBP20 and 80 have
      overlapping function in the same developmental pathway as SE and HYL1. Our
      results identify new components in miRNA biogenesis.

PMID- 18829591
TI  - Arginine metabolites in wound fluids from pressure ulcers: a pilot study.
AB  - Compelling evidence suggests that nitric oxide (NO*), a metabolite of arginine,
      plays an important role in wound healing. Arginine is a semi-essential amino acid
      that is metabolized by nitric oxide synthase and arginase. One model for wound
      healing regulation suggests the importance of strict reciprocal control of these
      enzymes in wounds. The purpose of this pilot study was to investigate arginine
      metabolism in wound fluids from patients with Stage III or IV pressure ulcers
      receiving negative pressure wound therapy (NPWT). Wound fluids were collected
      from 8 patients, aged 31-79 years, before and after initiation of NPWT on Days 1,
      3, and 7. Wound fluids were analyzed for nitrates/nitrites (NOx), arginine,
      citrulline, proline, and ornithine. There were no significant differences between
      NOx, arginine, citrulline, proline, and ornithine concentrations before and after
      initiation of NPWT among the various timepoints. However, we observed a downward
      trend of NO* levels from baseline to Day 7 of NPWT treatment. Furthermore, we
      detected a decrease in arginine levels over the study period, suggesting that the
      iNOS/citrulline pathway predominated during the first 72 hr of treatment, and the
      arginase/ ornithine pathway dominated thereafter. Arginine and its metabolites
      are detectable in wound fluids from patients with Stage III or IV pressure ulcers
      on NPWT. Further studies on chronic wounds are warranted to correlate wound
      healing outcomes with arginine metabolites at the cellular and molecular level
      over a longer period of time.

PMID- 18829592
TI  - Exogenous irritant-induced airway hyperreactivity and inhibition of soluble
      guanylyl cyclase.
AB  - The majority of nitric oxide (NO) effects in the respiratory system are caused by
      stimulation of soluble guanylyl cyclase (sGC) with subsequent increase of cyclic
      guanosine monophosphate (cGMP) production. The importance of this mechanism of NO
      action in airway hyperreactivity (AHR) pathogenesis is unknown. Therefore, the
      aim of our experiment was to examine the changes of airway reactivity enhanced by
      toluene vapor exposure in the presence or inhibition of sGC activity in guinea
      pigs. Animals were treated with a nonspecific sGC inhibitor, methylene blue, in a
      dose of 50 or 100 mg/kg body weight, administered by intraperitoneal injection 30
      min before or after exposure to toluene vapors. The toluene exposure lasted 2 hr
      in each of 3 consecutive days under in vivo conditions. Thereafter, the tracheal
      and lung tissue smooth muscle response to cumulative doses of mediators
      (histamine or acetylcholine) was recorded under in vitro conditions. The exposure
      to toluene vapors significantly increased the airway reactivity to both mediators
      in comparison with the healthy animal group. The administration of methylene blue
      decreased the amplitude of airway smooth muscle contraction in toluene-induced
      hyperreactivity. The decreases were dependent on the inhibitor doses, on a
      regimen of administration (before or after toluene inhalation), the level of the
      respiratory system (trachea, lung), and the bronchoconstrictor mediators. Our
      results suggest that the interaction between NO and sGC may be important for
      airway reactivity changes, but other mechanisms of NO action are important in AHR
      pathogenesis, too.

PMID- 18829589
TI  - Allostatic load and frailty in the women's health and aging studies.
AB  - BACKGROUND: Frailty involves decrements in many physiologic systems, is prevalent
      in older ages, and is characterized by increased vulnerability to disability and
      mortality. It is yet unclear how this geriatric syndrome relates to a preclinical
      cumulative marker of multisystem dysregulation. The purpose of this study was to
      evaluate whether allostatic load (AL) was associated with the geriatric syndrome
      of frailty in older community-dwelling women. METHODS: We examined the cross
      sectional relationship between AL and a validated measure of frailty in the
      baseline examination of two complementary population-based cohort studies, the
      Women's Health and Aging studies (WHAS) I and II. This sample of 728 women had an
      age range of 70-79. We used ordinal logistic regression to estimate the
      relationship between AL and frailty controlling for covariates. RESULTS: About
      10% of women were frail and 46% were prefrail. AL ranged from 0 to 8 with 91% of
      participants scoring between 0 and 4. Regression models showed that a unit
      increase in the AL score was associated with increasing levels of frailty (OR =
      1.16, 95% CI = 1.04-1.28) controlling for race, age, education, smoking status,
      and comorbidities. CONCLUSION: This study suggests that frailty is associated
      with AL. The observed relationship provides some support for the hypothesis that
      accumulation of physiological dysregulation may be related to the loss of reserve
      characterized by frailty.

PMID- 18829593
TI  - Cerebrospinal fluid apolipoprotein E, calcium and cerebral vasospasm after
      subarachnoid hemorrhage.
AB  - Intracellular calcium (Ca++) regulation of cerebral vessels is impaired after
      subarachnoid hemorrhage (SAH), making secondary pathways, such as that involving
      apolipoprotein E, potentially more influential. To evaluate cerebrospinal fluid
      (CSF) apolipoprotein E and Ca++ levels as biomarkers of cerebral vasospasm, we
      examined changes in levels over time and apolipoprotein E (APOE) epsilon4 allele
      presence after SAH in individuals with and without vasospasm. We hypothesized
      that individuals with low apolipoprotein E levels, increased Ca++ levels and/or
      at least one copy of the APOE epsilon4 allele would have vasospasm. Daily samples
      from 50 participants, aged 18-75, with SAH were used to quantify apolipoprotein E
      and Ca++ levels. Vasospasm was verified using cerebral angiogram and/or elevated
      transcranial Dopplers in combination with clinical neurologic deterioration.
      Overall apolipoprotein E levels were higher in individuals with the APOE epsilon4
      allele (p = .02) or angiographic vasospasm (p = .01), but there were no
      differences between individuals with and without symptomatic vasospasm. There
      were no significant changes in apolipoprotein E levels over time. Individuals
      with the epsilon4 allele had lower Ca++ levels (p = .02) with trends suggesting a
      different pattern of change over time (p = .07). CSF Ca++ levels were lower in
      individuals with symptomatic vasospasm (p < .01). Change in apolipoprotein E and
      Ca++ levels (p = .006) correlated over time regardless of genotype or vasospasm
      status. These findings suggest that apolipoprotein E and Ca++ may be interacting
      after SAH, but this interaction does not appear to influence vasospasm.

PMID- 18829594
TI  - Cerebrospinal fluid phospholipid changes following traumatic brain injury.
AB  - Traumatic brain injury (TBI) is a leading cause of morbidity and mortality, with
      approximately 1.4 million people suffering a TBI each year. With TBI, a cascade
      of events is initiated including the activation of phospholipases, which leads to
      the disruption of the lipid bilayer of the membrane of neurons and neuroglia. The
      purpose of this study is to describe phospholipid changes following TBI. A total
      of 39 cerebrospinal fluid samples were obtained from the ventricular catheter
      system of 10 participants who received a TBI as a result of a motor vehicle
      crash, being struck by a vehicle as a pedestrian, or a fall. Phospholipids were
      extracted from samples and measured by normal-phase high-performance liquid
      chromatography with ultraviolet detector at a wavelength of 206 nm. The highest
      mean concentration of lysophosphatidylcholine occurred on Day 1 after injury. The
      concentration of phosphatidylserine was variable, with the highest mean
      concentration occurring on Day 2 after injury. The highest mean concentrations of
      phosphatidylethanolamine, phosphatidylcholine, and sphingomyelin occurred on Day
      4 after injury. Findings provide preliminary evidence for disruption of central
      nervous system membrane phospholipids following TBI.

PMID- 18829595
TI  - White matter hyperintensities and medication adherence.
AB  - White matter hyperintensities (WMH) are associated with hypertension, age, and
      cognitive function, but the association between WMH and medication adherence has
      not been examined. The intent of this investigation was to consider the potential
      implications of hypertension-related brain morphological changes on medication
      adherence and thereby improve understanding of the self-management consequences
      of hypertension. The associations between WMH, blood pressure, age, cognitive
      function (specifically assessments of prefrontal function), and medication
      adherence were examined in 16 middle-aged and older adults self-managing at least
      one prescribed antihypertensive agent. Magnetic resonance imaging using an axial
      fluid attenuated inversion recovery (FLAIR) sequence was used to assess the
      presence of WMH. Cognitive assessments included measures of executive function,
      working memory, attention, and immediate recall. Adherence was monitored for 8
      weeks using electronic medication monitoring. More WMH were associated with
      poorer adherence (rs = -.25) and with higher systolic blood pressure (rs = .46),
      although these relationships were not statistically significant. WMH were
      associated with cognitive assessments in the expected direction including Digit
      Span Backward (rs = -.53, p < .05). Adherence was associated with immediate
      memory (rs = .54, p < .05) and inversely associated with failure to maintain set
      on the Wisconsin Card Sorting Test (WCST; rs = -.61, p < .05). These findings
      provide preliminary evidence for the association between WMH, assessments of
      prefrontal function, and medication adherence.

PMID- 18829596
TI  - Symptoms of postpartum depression associated with elevated levels of interleukin
      1 beta during the first month postpartum.
AB  - Postpartum depression (PPD) is a devastating disorder that may carry lifetime
      consequences. Although several psychosocial risks for PPD have been identified,
      biological contributors are unclear. Elevated inflammatory cytokines contribute
      to depression in nonpregnant, nonpostpartum populations; yet, their role in PPD
      has been minimally studied. The objective of this study is to determine whether
      inflammatory cytokines early in the postpartum period contribute to the
      development of PPD. Women were recruited within 24 hr of delivery, and 26
      provided urine for analysis of interleukin-1 beta (IL-1beta) and interleukin-6
      (IL-6) on postpartum days 7, 14, and 28. Participants completed a depression
      symptom survey (Centers for Epidemiologic Studies Depression Scale; CES-D) on Day
      28. An increase in IL-1beta was seen on Day 14 in women with symptoms of
      depression (CES-D > or = 11) on Day 28 compared to levels in women without
      depressive symptoms (F = 4.50, p = .045). These preliminary findings suggest
      elevated IL-1beta early in the postpartum period may increase the risk of PPD.
      Further studies involving a larger sample of women, including those clinically
      diagnosed with PPD, are required.

PMID- 18829597
TI  - Maternal heart rate variability and fetal behavior in hypertensive and
      normotensive pregnancies.
AB  - The relation between maternal heart rate variability (HRV) and fetal behavior was
      examined in hypertensive and normotensive pregnant women. A total of 40 mother
      fetal pairs (n = 20 normotensive mothers; n = 20 hypertensive mothers) at 33-41
      weeks' gestation were observed using a standardized procedure lasting
      approximately 50 min. It included the following measurements: maternal beat-by
      beat arterial blood pressure and HRV; spontaneous fetal heart rate (HR), body and
      breathing movements; and an estimate of amniotic fluid volume. The women in the
      hypertensive group had higher average body mass index (BMI) (33.7 vs. 28.8 kg/m2)
      than the normotensive group. In the normotensive group, there was no association
      between maternal HRV and fetal gestational age, HR, body or breathing movements.
      In the hypertensive group, maternal HRV measures of low-frequency, high
      frequency, and total power were associated with fetal gestational age; also,
      there was an association between maternal autonomic modulation of HR and fetal
      spontaneous HR. These findings suggest that the maternal autonomic system
      influences fetal cardiac function in pregnancies complicated by hypertension.

PMID- 18829598
TI  - Gestational diabetes mellitus: physical exercise and health outcomes.
AB  - PURPOSE: Gestational diabetes mellitus (GDM) is a serious complication of
      pregnancy associated with increased risk of adverse outcomes for both mother and
      infant. This study assesses the association of maternal exercise during GDM
      pregnancy and selected maternal and infant adverse GDM-related outcomes. The
      analysis uses information derived from the 1988 National Maternal Infant Health
      Survey (NMIHS) data. METHODS: Women in the 1988 NMIHS database were identified
      and grouped as to having experienced a non-GDM (n = 2,952,482) or GDM (n =
      105,600) pregnancy. Non-GDM and GDM groups were compared as to demographic and
      personal-attribute variables. The second part of this study focused on the women
      with GDM pregnancy, specifically a subset (n = 75,160) who met
      inclusion/exclusion criteria for the study of exercise during pregnancy. Each was
      categorized to either the exercise group or the nonexercise group. RESULTS: The
      non-GDM and GDM groups of pregnant women were not different as to the variables
      studied, except that older age and increased body mass index (BMI) were
      associated with GDM pregnancy. For the study of exercise during GDM pregnancy,
      the only variable that was associated with the exercise group was size of the
      infant. Participants in the exercise group were less likely than those in the
      nonexercise group to have delivered a large for gestational age (LGA) infant (F
      [1, 4314] = 9.82, p = .0017). IMPLICATIONS: The results of this study suggest
      that moderate maternal leisure time physical exercise during GDM pregnancy may
      reduce the risk of delivery of an LGA infant.

PMID- 18829599
TI  - A systematic review of exercise interventions in patients with heart failure.
AB  - The incidence of heart failure (HF) is increasing as the population ages.
      Pharmacotherapy is an important component of treatment and yields significant
      improvements in survival and quality of life. In recent decades, exercise has
      gradually become accepted as an intervention beneficial to patients with HF, but
      more information is needed to clarify the effects of exercise and optimize
      interventions. Therefore, a systematic review of randomized controlled trials
      published from 1966 to October 2006 was carried out via PubMed. About 69 trials
      were reviewed, which used as main outcome measures: (a) central hemodynamic
      parameters, (b) peripheral blood flow, (c) endothelial function, (d) activation
      of neurohormones and cytokine systems, (e) structure of and metabolism in
      skeletal muscles, and/or (f) quality of life. Study findings suggest that the
      favorable physiological responses to exercise might slow some of the
      pathophysiological progression of HF. However, most of the trials reviewed here
      were based on relatively small samples and selected participant groups, and the
      exercise programs varied widely. These limitations and inconsistencies need to be
      addressed through further studies. Furthermore, reliable strategies for
      maintaining the positive effects of exercise and extending them to patients'
      daily life and quality of life are scarce in these trials. These domains need
      further exploration through rationally designed, large-scale randomized
      controlled trials.

PMID- 18829600
TI  - The relationship between job stress and urinary cytokines in healthy nurses: a
      cross-sectional study.
AB  - Cytokines such as angiogenin (ANG) and interleukin (IL-8) have been shown to be
      related to depressive symptoms and inflammatory diseases like coronary heart
      disease. They may thus be used as stress biomarkers to identify and prevent
      health problems. To investigate the relationship between cytokines and nurses'
      job-related stress, levels of urinary ANG and IL-8 were measured in healthy
      female hospital nurses in Japan. The level of job-related stress of the subjects
      was evaluated using the Nursing Stress Scale (NSS), with the participants being
      classified into high- or low-stress groups for each subscale according to their
      scores. The participants' subjective psychological states were assessed using the
      Profile of Mood States--Short Form Japanese version (POMS-SFJ). Urinary ANG, IL
      8, and cortisol levels and subjective psychological states for two groups were
      compared for each NSS subscale. The fatigue and depression scores of POMS-SFJ
      subscales in the present study were higher than those of the general healthy
      Japanese population. Based on the mean score of the combined participants, nurses
      were experiencing the highest stress related to the pressure of having
      responsibility for patients' life support care (PPLC). Nurses reporting high
      levels of stress related to PPLC and conflict with physicians had high levels of
      urinary ANG. Urinary ANG levels may thus be associated with high levels of job
      stress.

PMID- 18829601
TI  - Significance of close surveillance of patients with peripheral arterial disease.
AB  - BACKGROUND: Peripheral arterial disease (PAD) indicates generalized
      atherosclerosis but is still underdiagnosed and undertreated. METHODS: Data were
      collected from patients with PAD from the Department of Cardiology and Angiology,
      University of Heidelberg, Germany. The prevalence of cardiovascular risk factors
      and medication were documented. RESULTS: Atherogenic risk factors, cardiovascular
      disease, and cerebrovascular disease were highly prevalent. By continuous care at
      the university clinic, in addition to family medicine treatment, the use of
      platelet inhibitors, antihypertensives, and lipid-lowering therapy was increased.
      Ankle-brachial index and walking distance improved. CONCLUSION: Long-term
      treatment at the university clinic had positive effects on atherogenic risk
      factors. The regular use of secondary preventive medication was improved. Still,
      this patient population remained undertreated and showed a high incidence of
      vascular event rates and a need for vascular interventions. This study implies
      the importance of both specialists and general practitioners in the care of these
      individuals.

PMID- 18829602
TI  - The first homozygous family for prothrombin G20210A polymorphism reported in
      Latin America.
AB  - The 20210A allele of the prothrombin gene is associated with increased risk of
      venous thromboembolism. In this study, we described manifestations of thrombosis
      in four generations of a Colombian family, with four 20210A homozygous carriers
      and six 20210G/A heterozygous carriers for polymorphism as well as unrelated
      participants from the same population. The levels of prothrombin in the 20210A
      homozygote patients were higher than in the normal 20210G homozygotes (133 + 11%
      and 92.3 + 12.4%, respectively, P < .01) and the 20210G/A heterozygotes (133 +
      11% vs. 114.8 + 24%, P < .05). About 2 out of 4 20210A homozygotes and 5 out of 6
      20210G/A heterozygous members of this family did not have venous thromboembolism
      or any other thrombotic manifestation even though one of them had been exposed to
      thrombotic risk factors. Thus, we posit the effect of 20210A on the thrombotic
      phenotype in this family seems to be weak.

PMID- 18829603
TI  - Rereading ratios.

PMID- 18829604
TI  - The current state of nursing performance measurement, public reporting, and value
      based purchasing.
AB  - Over the last decade, there has been a substantial investment in holding health
      care providers accountable for the quality of care provided in hospitals and
      other settings of care. This investment has been realized through the
      proliferation of national policies that address performance measurement, public
      reporting, and value-based purchasing. Although nurses represent the largest
      segment of the health care workforce and despite their acknowledged role in
      patient safety and health care outcomes, they have been largely absent from
      policy setting in these areas. This article provides an analysis of current
      nursing performance measurement and public reporting initiatives and presents a
      summary of emerging trends in value-based purchasing, with an emphasis on
      activities in the United States. The article synthesizes issues of relevance to
      advancing the current climate for nursing quality and concludes with key issues
      for future policy setting.

PMID- 18829605
TI  - The Oregon Consortium for Nursing Education: a response to the nursing shortage.
AB  - The Oregon Consortium for Nursing Education (OCNE) is a statewide coalition
      designed as a long-term solution to the nursing shortage and in response to the
      need for a new kind of nurse to care for Oregon's aging and increasingly diverse
      population. It is an effort to increase capacity in schools of nursing by making
      the best use of scarce faculty, classrooms, and clinical training resources in
      the delivery of a standard curriculum on 13 campuses, including 8 community
      colleges and the 5 campuses of the OHSU School of Nursing. This article describes
      the development of OCNE, including infrastructure development, creation of the
      shared curriculum, redesign of clinical education, faculty development, and plans
      for evaluation. If OCNE is successful in achieving its goals, it holds
      substantial policy implications for the development of nursing education systems,
      design of curricula, use of simulation as a component of clinical education, and
      delivery of clinical education.

PMID- 18829607
TI  - Radiofrequency energy delivery to the lower esophageal sphincter (Stretta
      procedure) does not provide long-term symptom control.
AB  - The Stretta procedure (radiofrequency energy application to the lower esophageal
      sphincter) is a unique endoluminal technique for the management of
      gastroesophageal reflux. This article reports on the long-term effectiveness of
      the Stretta procedure in patients with significant gastroesophageal reflux
      disease (GERD) referred to a surgical practice. Patients who underwent Stretta
      with a minimum of 36 months follow-up were included. Thirty-two patients with an
      average follow-up of 53 months were included; 19 proceeded to anti-reflux
      surgery. Those not undergoing surgery showed a significant improvement in their
      GERD satisfaction from 3.14 to 1.46 (P = .0006) but had significantly lower
      preprocedure heartburn scores (2.43) than those who proceeded to surgery (3.66, P
      = .0401). The Stretta procedure was effective in reducing symptoms in 40% of
      patients. Responders had less severe preoperative heartburn. Radiofrequency
      energy delivery to the lower esophageal sphincter may be effective in selected
      patients for the treatment of gastroesophageal reflux.

PMID- 18829608
TI  - Mortality and diabetes mellitus in amputations of the lower limbs for gas
      gangrene: a case report.
AB  - The aim of this study was to examine any association between the presence of
      diabetes in patients with gas gangrene of the legs and mortality following major
      lower limb amputation. In a retrospective study, patients submitted to amputation
      of lower limbs for anaerobic infections were evaluated in the period from January
      2005 to January 2007 in the University Hospital de Base in Sao Jose do Rio Preto.
      All the patients were hospitalized for the treatment of ulcerated lesions of the
      leg. The study sample consisted of 30 men and 10 women aged between 46 and 87
      years (mean 69 years) suffering from anaerobic infections. During treatment, the
      presence of crepitation in the skin was observed as was gas by radiological
      examination. Amputation was performed within 2 to 6 hours after diagnosis.
      Diabetes was identified in 33 patients and death occurred within the
      perioperative period in 12 cases. Diabetes is associated with the necessity of
      amputation for gas gangrene resulting in a high mortality rate.

PMID- 18829609
TI  - Possibilities and limitations of a miniaturized long-term extracorporeal life
      support system as bridge to transplantation in a case with biventricular heart
      failure.
AB  - In cardiac surgery extracorporeal life support systems (ECLS), also known as
      extracorporeal membrane oxygenation systems (ECMO), are often placed in case of
      postcardiotomy shock, until the patient's myocardial pump function recovers.
      Patients under ECLS are typically intubated and immobilized. We present a 57-year
      old man suffering from severe ischemic cardiomyopathy in biventricular failure
      and intractable cardiogenic shock, who was supported with a miniaturized
      cardiopulmonary bypass system (MECC((R))) installed as venoarterial ECLS for 37
      days. The patient was fully awake, spontaneously breathing, and practicing
      exercise in bed during life support for four weeks. He then required intubation
      for pneumonia, but later underwent successful transplantation. In conclusion,
      this case demonstrates that ECLS with miniaturized heart-lung machines offer the
      possibility of prolonged and safe support, ideal as a bridge to decision in
      patients with cardiogenic shock. On the other side, this report also indicates
      that ECLS is not recommended as a bridge to transplantation on a routine basis.

PMID- 18829610
TI  - Elevated resting and agonist-induced whole blood chemiluminescence in patients
      with active infective endocarditis.
AB  - Infective endocarditis (IE) and surgical procedures related to cardiac surgery
      are accompanied by inflammatory responses that may alter production of oxidants
      by phagocytes. This study evaluates luminol enhanced whole blood
      chemiluminescence (LBCL) as a measure of oxidative production by circulating
      phagocytes in 26 IE patients in comparison to 27 matched patients with acquired
      valvular heart disease and 25 healthy controls. Blood was collected the day
      before and 3, 7, 12 and 21 days after valve replacement surgery for LBCL
      measurement; resting (rCL) and agonist (fMLP)-stimulated total light emission
      (tCL). Preoperative rCL and tCL with values observed after 3, 7, 14, and 21 days
      from surgery were higher (P<0.01) in patients with IE than in healthy controls.
      Median preoperative rCL, and tCL was about 2.5-times higher (P<0.01) in IE group
      than in patients with valvular heart disease (4.3 vs. 1.7 U/10(4) phagocytes and
      2473 vs. 782 Uxs/10(4) phagocytes). Three days after valve replacement, LBCL rose
      three times (P<0.01) in both operated groups. With patient recovery, LBCL
      decreased and no differences were noted between groups. Patients with IE had
      elevated LBCL reflecting increased oxidants release from circulating phagocytes
      that may predispose to the development of oxidative stress.

PMID- 18829611
TI  - High resting heart rate: a cardiovascular risk factor or a marker of risk?

PMID- 18829612
TI  - Triple risk: do difficult temperament and family conflict increase the likelihood
      of behavioral maladjustment in children born low birth weight and preterm?
AB  - OBJECTIVE: This study examined the impact of family conflict on internalizing and
      externalizing behavior at age 8 for children born low birth weight (LBW) and
      preterm (PT), with specific attention to the moderating role of early
      temperament. METHODS: The sample included 728 families enrolled in the
      longitudinal study of the Infant Health and Development Program. The study relied
      on maternal reports of child temperament at age 1, family conflict at age 6(1/2)
      years and 8 years, and child behavior at age 8 years. RESULTS: Children exposed
      to high levels of family conflict had more internalizing problems. Child
      temperament assessed in infancy moderated the impact of family conflict on
      externalizing but not internalizing problem behavior. DISCUSSION: LBW/PT children
      with a difficult temperament are more at risk for poor developmental outcomes,
      such as externalizing behavior problems, when exposed to family conflict than
      children with a less difficult temperament.

PMID- 18829613
TI  - Calcitriol ameliorates capillary deficit and fibrosis of the heart in subtotally
      nephrectomized rats.
AB  - BACKGROUND: Remodelling of the heart, characterized by hypertrophy, fibrosis and
      capillary/myocyte mismatch, is observed in patients with chronic renal failure.
      Low vitamin D levels have been associated with increased cardiovascular risk. In
      the present experimental study, we studied the effects of non-hypercalcaemic
      doses of calcitriol on microvascular disease and interstitial fibrosis of the
      heart. METHODS: Three-month-old male Sprague-Dawley rats were randomized to
      subtotal nephrectomy (SNX) or sham operation and received calcitriol (6 ng/kg) or
      vehicle starting immediately thereafter. Blood pressure was measured by tail
      pletysmography. Albuminuria was measured by rat-specific ELISA. Capillary length
      density, volume density of interstitial tissue, immunohistochemistry and western
      blots (vitamin D receptor, collagen I, III, TGF-beta(1), MAP kinases and
      nitrotyrosine) were assessed after 12 weeks of treatment. RESULTS: After SNX
      blood pressure, albuminuria and heart weight were elevated, capillary length
      density reduced and interstitial fibrosis increased. Treatment with calcitriol
      reduced albuminuria and prevented reduction of capillary density and expansion of
      interstitium without affecting significant blood pressure and heart weight after
      perfusion fixation. Calcitriol left high VEGF unchanged, but upregulated VEGF
      receptor 2 (presumably reversing VEGF resistance). Calcitriol reduced expression
      of profibrotic TGF-beta(1) and the accumulation of collagens I and III.
      CONCLUSIONS: Non-hypercalcaemic doses of calcitriol ameliorated, directly or
      indirectly, cardiac remodelling in sub- totally nephrectomized rats.

PMID- 18829614
TI  - Regulation of connective tissue growth factor (CTGF) by hepatocyte growth factor
      in human tubular epithelial cells.
AB  - BACKGROUND: Hepatocyte growth factor (HGF) is a pleiotropic protein with
      renoprotective functions, which have been attributed at least in part to its
      ability to counteract the profibrotic effects of transforming growth factor beta
      (TGF-beta). A major downstream mediator of TGF-beta is connective tissue growth
      factor (CTGF). However, the molecular mechanisms of CTGF regulation by HGF have
      not yet been investigated. METHODS: CTGF expression was analysed in human primary
      tubular epithelial cells (hPTECs) and the cell line HKC-8 by western blotting.
      Morphological alterations were analysed by immunocytochemistry. RESULTS: HGF
      induced a transient expression of CTGF, which was maximal after 6 h and returned
      to baseline after 24 h. Coincubation with TGF-beta increased CTGF protein at 6 h,
      whereas HGF significantly decreased CTGF induction by TGF-beta after 24 h.
      Furthermore, HGF induced cell scattering associated with reorganization of focal
      adhesions and formation of lamellipodia and filopodia. The early induction of
      CTGF was linked to the HGF-mediated alterations of cell morphology. The PP2
      inhibitor of Src-family kinases, which regulate focal adhesion turnover, reduced
      HGF-mediated upregulation of CTGF. In addition, inhibition of the Rho-kinase,
      which modulates the actin cytoskeleton, impaired CTGF expression. Combination of
      both inhibitors further decreased CTGF expression. Comparable inhibitory effects
      were obtained, when CTGF was induced by the combination of HGF and TGF-beta.
      CONCLUSIONS: We provide evidence for a dual effect of HGF on CTGF regulation in
      human tubular epithelial cells: transient upregulation of CTGF in the absence of
      TGF-beta, which was related to alterations of cell morphology, and interference
      with TGF-beta-mediated CTGF induction after prolonged incubation.

PMID- 18829615
TI  - Change in MRI-detected subchondral bone marrow lesions is associated with
      cartilage loss: the MOST Study. A longitudinal multicentre study of knee
      osteoarthritis.
AB  - OBJECTIVES: To describe the natural history of subchondral bone marrow lesions
      (BMLs) in a sample of subjects with knee osteoarthritis (OA) or at risk of
      developing it. Additionally, to examine the association of change in BMLs from
      baseline to 30-month follow-up with the risk of cartilage loss in the same
      subregion at follow-up. METHODS: 1.0 T MRI was performed using proton density
      weighted, fat-suppressed sequences. BML size and cartilage status were scored in
      the same subregions according to the WORMS system. Subregions were categorised
      based on comparison of baseline and follow-up BML status. A logistic regression
      model was used to assess the association of change in BML status with cartilage
      loss over 30 months using stable BMLs as the reference group. RESULTS: 395 knees
      were included. 66% of prevalent BMLs changed in size; 50% showed either
      regression or resolution at follow-up. The adjusted odds ratios (95% confidence
      intervals) of cartilage loss in the same subregion at follow-up for the different
      groups were 1.2 (0.5 to 1.6) for regressing BMLs, 0.9 (0.5 to 1.6) for resolving
      BMLs, 2.8 (1.5 to 5.2) for progressing BMLs, 0.2 (0.1 to 0.3) for subregions with
      no BMLs at baseline and follow-up and 3.5 (2.1 to 5.9) for newly developing BMLs.
      BML size at baseline was associated with risk of subsequent cartilage loss.
      CONCLUSIONS: The majority of pre-existing BMLs decreased in size at follow-up.
      Absence of BMLs was associated with a decreased risk of cartilage loss, while
      progressing and new BMLs showed a high risk of cartilage loss in the same
      subregion.

PMID- 18829616
TI  - Impact of adalimumab on work participation in rheumatoid arthritis: comparison of
      an open-label extension study and a registry-based control group.
AB  - BACKGROUND AND OBJECTIVES: Rheumatoid arthritis (RA) causes considerable
      disability and often results in loss of work capacity and productivity. This
      study evaluated the impact of adalimumab, a tumour necrosis factor antagonist
      with demonstrated efficacy in RA, on long-term employment. METHODS: Data from an
      open-label extension study (DE033) of 486 RA patients receiving adalimumab
      monotherapy who previously did not respond to at least one disease-modifying
      antirheumatic drug (DMARD) and had baseline work status information were compared
      with data from 747 RA patients receiving DMARD treatment in a Norway-based
      longitudinal registry. Primary outcomes included the time patients continued
      working at least part time and the likelihood of stopping work. Secondary
      outcomes included American College of Rheumatology (ACR) and European League
      Against Rheumatism (EULAR) responses and disease remission. Outcomes were
      compared 6, 12 and 24 months after enrolment. RESULTS: During a 24-month period,
      the 158 patients who received adalimumab and were working at baseline worked 7.32
      months longer (95% CI 4.8 to 9.1) than did the 180 patients treated with DMARDs,
      controlling for differences in baseline characteristics. Regardless of baseline
      work status, patients receiving adalimumab worked 2.0 months longer (95% CI 1.3
      to 2.6) and were significantly less likely to stop working than those receiving
      DMARDs (HR 0.36 (95% CI -0.30 to 0.42) for all patients and 0.36 (95% CI 0.15 to
      0.85) for patients working at baseline, respectively). The patients who received
      adalimumab were also considerably more likely to achieve ACR responses and
      disease remission than DMARD-treated patients. Patients who achieved EULAR good
      response and remission were less likely to stop working, but this relationship
      was only seen in patients receiving DMARDs. CONCLUSIONS: Patients with RA who
      received adalimumab experienced considerably longer periods of work and
      continuous employment, and greater rates of clinical responses, than patients
      receiving DMARDs. The mechanism by which adalimumab decreases likelihood of
      stopping work seems to be different from that of DMARD treatment and independent
      of clinical responses.

PMID- 18829617
TI  - Neonatal extracorporeal membrane oxygenation: practice patterns and predictors of
      outcome in the UK.
AB  - OBJECTIVE: To review the UK neonatal extracorporeal membrane oxygenation (ECMO)
      service and identify predictors of outcome. DESIGN: Retrospective review of the
      national cohort. PATIENTS AND INTERVENTIONS: 718 neonates received ECMO for
      respiratory failure between 1993 and 2005. MEASUREMENTS AND RESULTS: Diagnoses
      were: 48.0% meconium aspiration syndrome (97.1% survivors), 15.9% congenital
      diaphragmatic hernia (CDH; 57.9% survivors), 15.9% sepsis (62.3% survivors), 9.5%
      persistent pulmonary hypertension (79.4% survivors), 5.6% respiratory distress
      syndrome (92.5% survivors) and 5.1% congenital lung abnormalities (24.3%
      survivors). The overall survival rate of 79.7% compared favourably with the
      worldwide Extracorporeal Life Support Organization (ELSO) Registry. Over the
      period of review, pre-ECMO use of advanced respiratory therapies increased
      (p<0.001), but ECMO initiation was not delayed (p = 0.61). The use of veno-venous
      (VV) ECMO increased (p<0.001) and average run time fell (p = 0.004). Patients
      treated with VV ECMO had a survival rate of 87.7% compared with 73.4% in the veno
      arterial (VA) ECMO group; only 42.4% of those needing conversion from VV to VA
      ECMO survived. In non-CDH neonates, lower birth weight, lower gestational age,
      older age at ECMO and higher oxygenation index (OI) were associated with
      increased risk of death. In CDH neonates, lower birth weight and younger age at
      ECMO were identified as risk factors for death. CONCLUSION: The UK neonatal ECMO
      service achieves good outcomes and with overall survival rate reaching 80%
      compares favourably with international results. Advanced respiratory therapies
      are used widely in UK ECMO patients. Identification of higher OI and older age at
      ECMO as risk factors in non-CDH neonates reinforces the importance of timely
      referral for ECMO.

PMID- 18829618
TI  - Infant feeding, solid foods and hospitalisation in the first 8 months after
      birth.
AB  - Most infants in the UK start solids before the recommended age of 6 months. We
      assessed the independent effects of solids and breast feeding on the risk of
      hospitalisation for infection in term, singleton infants in the Millennium Cohort
      Study (n = 15,980). For both diarrhoea and lower respiratory tract infection
      (LRTI), the monthly risk of hospitalisation was significantly lower in those
      receiving breast milk compared with those receiving formula. The monthly risk of
      hospitalisation was not significantly higher in those who had received solids
      compared with those not on solids (for diarrhoea, adjusted odds ratio 1.39, 95%
      CI 0.75 to 2.59; for LRTI, adjusted odds ratio 1.14, 95% CI 0.76 to 1.70), and
      the risk did not vary significantly according to the age of starting solids.

PMID- 18829619
TI  - Atopic dermatitis in premature and term children.
AB  - OBJECTIVE: To investigate the prevalence of atopic dermatitis (AD) in premature
      compared with term children, the frequency of food allergy in children with AD,
      and the possible differences in prevalence of AD in children delivered by
      caesarean section compared with vaginally delivered children. DESIGN: Prospective
      follow-up study over 2 years. METHOD: 609 children (193 premature and 416 term)
      were included. At 2 years, 512 children (161 premature and 351 term)
      participated. Children with symptoms consistent with AD/possible food allergy
      were examined, and the dermatitis was evaluated according to the SCORAD index.
      Skin prick test, specific IgE, elimination/challenge and DBPC challenge were
      performed. RESULTS: 18.6% (95/512) of the children (19.9% (32/161) premature and
      17.9% (63/351) term) had a diagnosis of AD. The prevalence of adverse reactions
      to food in all the children with AD was 15.8% (15/95) (similar in preterm and
      term children). AD was found in 17.5% (30/171) of children delivered by caesarean
      section, and 19.1% (65/341) delivered vaginally CONCLUSIONS: The prevalence of AD
      in the first 2 years of life was 18.6%, with no significant difference between
      preterm and term children. Adverse reactions to food were found in 15.8% (a
      similar prevalence in premature and term children). Mode of delivery did not
      affect prevalence of AD.

PMID- 18829620
TI  - When should oxygen be given to children at high altitude? A systematic review to
      define altitude-specific hypoxaemia.
AB  - BACKGROUND: Acute respiratory infections (ARI) cause 3 million deaths in children
      worldwide each year. Most of these deaths occur from pneumonia in developing
      countries, and hypoxaemia is the most common fatal complication. Simple and
      adaptable indications for oxygen therapy are important in the management of ARI.
      The current WHO definition of hypoxaemia as any arterial oxygen saturation
      (SpO(2)) <90% does not take into account the variation in normal oxygen
      saturation with altitude. This study aimed to define normal oxygen saturation and
      to estimate the threshold of hypoxaemia for children permanently living at
      different altitudes. METHODS: We carried out a systematic review of the
      literature addressing normal values of oxygen saturation in children aged 1 week
      to 12 years. Hypoxaemia was defined as any SpO(2) at or below the 2.5th centile
      for a population of healthy children at a given altitude. Meta-regression
      analysis was performed to estimate the change in mean SpO(2) and the hypoxaemia
      threshold with increasing altitude. RESULTS: 14 studies were reviewed and
      analysed to produce prediction equations for estimating the expected mean SpO(2)
      in normal children, and the threshold SpO(2) indicating hypoxaemia at various
      altitudes. An SpO(2) of 90% is the 2.5th centile for a population of healthy
      children living at an altitude of approximately 2500 m above sea level. This
      decreases to 85% at an altitude of approximately 3200 m. CONCLUSIONS: For health
      facilities at very high altitudes, giving oxygen to all children with an SpO(2)
      <90% may be too liberal if oxygen supplies are limited. In such settings, Spo(2)
      <85% may be more appropriate to identify children most in need of oxygen
      supplementation.

PMID- 18829621
TI  - Induced sputum or gastric lavage for community-based diagnosis of childhood
      pulmonary tuberculosis?
AB  - OBJECTIVES: To compare the diagnostic yield of Mycobacterium tuberculosis from
      induced sputum (IS) and gastric lavage (GL) among children in a community
      setting. METHODS: Specimen-collection methods for bacteriological confirmation of
      pulmonary tuberculosis (PTB) were compared during a tuberculosis vaccine trial
      near Cape Town, South Africa (2001-2006). Children with a tuberculosis contact or
      compatible symptoms were investigated for suspected PTB. Diagnostic yields from
      764 paired IS and GL specimens were compared in 191 culture-confirmed cases.
      MEASUREMENTS AND MAIN RESULTS: The crude yield of M tuberculosis was 10.4%, n =
      108 by IS (5.8%) and n = 127 by GL (6.8%), from a total of 194 cases, of which
      three had incomplete IS/GL specimen pairs. Agreement between IS and GL was poor
      (kappa = 0.31). The comparative yield of a single IS sample (38%) was equivalent
      to a single GL sample (42%), with a difference in yield of -4% (95% CI -15% to
      +7%). The combined yield of same-day IS and GL specimens (67%) was equivalent to
      two consecutive GL specimens (66%), with a difference in yield of 1% (95% CI -9%
      to 11%), but significantly greater than two consecutive IS specimens (55%), with
      a difference in yield of 12% (95% CI 2% to 21%). The adjusted odds of a M
      tuberculosis culture were increased by a positive tuberculin skin test or chest
      radiograph compatible with PTB. CONCLUSIONS: In this community setting, the
      diagnostic yield of a single IS sample was equivalent to that of a single GL
      sample. The optimal diagnostic yield may be obtained from paired IS and GL
      specimens taken on a single day or two GL specimens taken on consecutive days.

PMID- 18829622
TI  - Minimising medication errors in children.
AB  - Medical errors are a major problem in the UK and other countries. Apart from the
      direct expense to the healthcare system, there are great personal costs to those
      involved including patients, their families and staff, and public confidence is
      undermined. Therefore, policy initiatives have been implemented to reduce such
      mistakes. Medication errors are thought to be the most common type of medical
      errors, with the majority of studies being conducted in adults. However, recent
      evidence highlights the fact that medication errors are also a significant
      problem in the paediatric population. This paper reviews the factors contributing
      to paediatric medication errors, including lack of appropriate paediatric
      formulations, communication issues between health professionals, dose calculation
      mistakes and inadequate clinical practice. This review will also discuss risk
      reduction strategies such as electronic prescribing and computerised physician
      order entry (CPOE) systems which can significantly reduce paediatric medication
      errors in conjunction with pharmacist monitoring, improved communication and
      environments which promote best practice.

PMID- 18829623
TI  - Prospective follow-up oral food challenge in food protein-induced enterocolitis
      syndrome.
AB  - OBJECTIVES: To determine tolerance rates to cow's milk and soy and to suggest
      guidelines for follow-up oral food challenges (FU-OFCs) in infantile food protein
      induced enterocolitis syndrome (FPIES). METHODS: The authors analysed the data of
      23 patients with infantile FPIES who underwent two or more FU-OFCs and were
      followed up until over 2 years of age. The first FU-OFCs were performed at 6
      months of age, and patients were randomly allocated to cow's milk (n = 11) or soy
      (n = 12) challenge starting groups. Second and third FU-OFCs were performed at 2
      month intervals in a crossed and switched-over manner. RESULTS: Tolerance rates
      to cow's milk and soy were 27.3% and 75.0% at 6 months of age, 41.7% and 90.9% at
      8 months and 63.6% and 91.7% at 10 months, respectively. Patients outgrew cow's
      milk and soy intolerance at age 20 and 14 months. CONCLUSIONS: In infantile
      FPIES, the first FU-OFC should be performed with soy at 6-8 months of age and
      cow's milk FU-OFC should be conducted at over 12 months of age. Infants with
      FPIES were observed to outgrow food sensitivities during the first 2 years of
      life.

PMID- 18829624
TI  - Specialist registrars' views on their teaching role.
AB  - This study looks at whether UK specialist registrars (SpRs) are involved in
      teaching and meeting their educational obligations. A questionnaire was
      distributed to all 133 paediatric SpRs in the region. 92% responded (122/133).
      All SpRs reported doing some teaching with nearly all teaching junior trainees
      and students. During daytime hours, 41% of trainees taught for 1 h per week but
      half this time at night with 21% reporting doing no teaching out of hours. 55%
      had formal educational training most commonly a "Teach the Teacher" course.
      Developing SpRs as educators was felt to be best achieved through mandatory
      training (61%, 74) and themed regional SpR training days (61%, 74). SpRs are
      making an important contribution to education. Teaching competences should be
      included in the personal development plan of all trainees and rostered time
      allocated to SpRs specifically to teach.

PMID- 18829625
TI  - Commentary on in-transit lymph node metastases in breast cancer: a possible
      source of local recurrence after Sentinel Node procedure.

PMID- 18829626
TI  - Confirmation of BD ProbeTec Neisseria gonorrhoeae reactive samples by Gen-Probe
      APTIMA assays and culture.
AB  - BACKGROUND: Use of nucleic acid amplification tests (NAATs), such as strand
      displacement assay (SDA), for the detection of gonococcal infection in low
      prevalence populations is controversial because of the likelihood of false
      positive results. Use of supplementary NAATs with alternative target sites has
      been recommended for confirmation of primary NAAT results. AIM: To evaluate if
      SDA reactive specimens for Neisseria gonorrhoeae, which were either culture
      positive or negative, can be confirmed by alternative target NAATs such as
      transcription-mediated assays (TMA). METHODS: SDA reactive specimens were
      retested by TMA using APTIMA Combo 2 (AC2) and APTIMA GC (AGC) assays. Two
      different methods of specimen preparation were used to test the specimens. In
      method A, residual extract after SDA was retested and in method B, the original
      clinical specimen was re-extracted in TMA medium and then retested. Cervical or
      urethral swabs were requested to confirm the SDA results by culture. RESULTS: By
      method A, 26/49 (53.1%) of SDA positive specimens were positive by AC2 and/or
      AGC; 14/27 (51.8%) culture confirmed SDA positive tests were positive by AC2
      and/or AGC. By method B, 38/39 (97.3%) SDA positive results were confirmed by
      both AC2 and AGC. All the 25 culture confirmed SDA positive tests were confirmed
      by both AC2 and AGC; 5/6 SDA positive tests that were culture negative were
      confirmed by both AC2 and/AGC. CONCLUSION: Alternative target site NAATs, such as
      AC2 and AGC, can be used to confirm SDA positive results using the same clinical
      specimen. There is high concordance between the three NAATs.

PMID- 18829627
TI  - Structural and metabolic brain abnormalities in preclinical cerebral autosomal
      dominant arteriopathy with subcortical infarcts and leucoencephalopathy.
AB  - OBJECTIVE: To assess, by using quantitative MRI metrics, structural and metabolic
      brain abnormalities in subjects with preclinical cerebral autosomal dominant
      arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL).
      BACKGROUND: Brain MRI abnormalities have been occasionally reported in
      preclinical CADASIL subjects. However, very little is known as to when the brain
      tissue damage starts to accumulate, what brain regions are primarily involved and
      whether the brain damage is significant in subjects who have no overt clinical
      manifestations of the disease. METHODS: Twelve subjects (mean age 40 years; range
      26-55 years; males/females 6/6) with genetically proven CADASIL and no clinical
      signs of the disease underwent conventional MRI and proton MR spectroscopic
      imaging ((1)H-MRSI) to measure white matter (WM) lesion volume (LV), global and
      regional cerebral volumes, and WM levels of N-acetylaspartate (NAA) normalised to
      creatine (Cr). MR values were compared with those of 13 age- and sex-matched
      healthy controls. RESULTS: All preclinical CADASIL showed WM lesions (range 0.2
      to 26 cm(3)). They were mostly distributed in the frontal and parietal regions,
      with the highest probability in the corona radiata. On (1)H-MRSI examination,
      NAA/Cr values were lower in preclinical CADASIL than in HC, particularly in the
      corona radiata (p<0.01). Normalised brain and cortical volumes were also lower in
      preclinical CADASIL than in HC (p<0.01), particularly in the frontal cortex.
      CONCLUSIONS: The pathological process occurring in CADASIL leads to damage of WM
      and neocortex much before the evidence of clinical symptoms. At this preclinical
      stage, this seems to take place prevalently in the frontal brain region.

PMID- 18829628
TI  - CSF oligoclonal band status informs prognosis in multiple sclerosis: a case
      control study of 100 patients.
AB  - OBJECTIVE: Oligoclonal band (OCB) negative multiple sclerosis (MS) is well
      recognised but uncommon, studied in only a few usually small case series. These
      reached differing conclusions on whether its clinical features or course differ
      from OCB positive disease. The study hypothesis was that a definitive study would
      not only be of clinical and prognostic value but also potentially offer
      information about the possible role of CSF oligoclonal immunoglobulins in MS
      disease processes. METHODS: A collaborative cohort of well documented patients in
      southwest England and south Wales was used to identify and analyse a large group
      of patients with OCB negative MS and make comparisons with age and sex matched
      OCB positive controls. RESULTS: An approximate minimum 3% of patients with MS
      were OCB negative. They were significantly more likely to exhibit neurological or
      systemic clinical features atypical of MS (headaches, neuropsychiatric features
      and skin changes). Non-specific MRI, blood and (other) CSF abnormalities were
      also more common, emphasising the need for continued diagnostic vigilance,
      although the incautious application of McDonald diagnostic criteria in OCB
      negative cases renders categorisation as "definite" MS more likely. Studying the
      uniformly assessed Cardiff group (69 patients), we found the prognosis for
      neurological disability was significantly better for OCB negative cases. The age
      adjusted hazard ratio for OCB negative and OCB positive subjects to reach
      Disability Scale Status (DSS) 4 and DSS 6 was, respectively, 0.60 (95% CI 0.39 to
      0.93; p = 0.02) and 0.51 (95% CI 0.27 to 0.94; p = 0.03). CONCLUSION: There are
      clear clinical differences between OCB negative and OCB positive MS, in
      particular a better prognosis for disability. This is consistent with a secondary
      but nonetheless contributory role in disease process for intrathecally
      synthesised immunoglobulins.

PMID- 18829629
TI  - Memory impairment in multiple sclerosis: correlation with deep grey matter and
      mesial temporal atrophy.
AB  - BACKGROUND: MRI research in multiple sclerosis (MS) samples reveals pathology in
      both the cerebral cortex and deep grey matter (DGM). The classical subcortical
      dementia hypothesis has been ascribed to MS and is supported by studies
      highlighting the role of thalamic atrophy in neuropsychological outcomes.
      However, the importance of mesial temporal lobe (MTL) atrophy in MS is largely
      untested and poorly understood. New structural imaging techniques permit
      volumetric measures of multiple regions within the MTL lobe and DGM. OBJECTIVE:
      To determine the relative importance of MTL and DGM structures in predicting MS
      performance on memory tests presented in the auditory/verbal and visual/spatial
      spheres. METHODS: Cross sectional analysis of 50 patients with MS undergoing
      structural brain MRI and neuropsychological testing. Using Freesurfer software,
      the volumes of the MTL (hippocampus, amygdala) and DGM (thalamus, caudate)
      structures were calculated and compared with control values. Neuropsychological
      testing contributed measures of new learning, delayed recall and recognition
      memory, in the auditory/verbal and visual/spatial memory modalities. RESULTS:
      Significant correlations between lower regional volume and poorer test
      performance were observed across all memory tests. For measures of free recall or
      new learning, DGM volumes were most strongly predictive of outcomes. In contrast,
      measures of recognition memory were predicted only by MTL volumetric measures.
      CONCLUSION: For the first time, the predictive validity of MTL and DGM atrophy
      were simultaneously compared with MS using reliable and validated
      neuropsychological measures. This study found that both compartments play
      significant but different roles in the amnesia of MS.

PMID- 18829630
TI  - Regional variations in the extent and pattern of grey matter demyelination in
      multiple sclerosis: a comparison between the cerebral cortex, cerebellar cortex,
      deep grey matter nuclei and the spinal cord.
AB  - BACKGROUND: Substantial grey matter (GM) demyelination occurs in both the
      cerebral cortex and spinal cord in multiple sclerosis (MS). GM demyelination also
      occurs in the cerebellar cortex and the deep GM nuclei of the brain. However, no
      study has made a direct "within subject" comparison of the extent of GM pathology
      between these regions. AIM: To examine the extent and pattern of GM demyelination
      in the motor cortex, cingulate gyrus, cerebellum, thalamus and spinal cord in MS.
      METHODS: Postmortem study using material from 14 MS cases and three controls.
      Sections were taken from the five predetermined areas and stained for proteolipid
      protein. The extent of GM and white matter (WM) demyelination was assessed in
      each region. RESULTS AND CONCLUSION: Overall, 28.8% of the GM was demyelinated
      compared with 15.6% of the WM (p<0.001), with demyelination being greater in the
      GM than in the WM at each of the anatomical sites. There was substantial
      variation in the extent of demyelination between the different CNS regions. GM
      demyelination was most extensive in the spinal cord and cerebellum while WM
      demyelination was most prominent in the spinal cord.

PMID- 18829631
TI  - Corticosteroids for bacterial corneal ulcers.
AB  - AIMS: The aim of the study was to conduct a preliminary clinical trial to assess
      whether adjunctive topical corticosteroids improve outcomes in bacterial
      keratitis and, if no difference was found, to determine the feasibility and
      sample size necessary for conducting a larger trial to answer this question.
      METHODS: In this single centre, double-masked clinical trial, 42 patients with
      culture-confirmed bacterial keratitis at Aravind Eye Hospital in India were
      randomised to receive either topical prednisolone phosphate or placebo. All
      patients received topical moxifloxacin. The primary outcome was best spectacle
      corrected visual acuity (BSCVA) at 3 months, adjusting for enrolment BSCVA and
      arm. Other pre-specified outcomes included re-epithelialisation time,
      infiltrate/scar size and adverse events. RESULTS: Compared with placebo, patients
      in the steroid group re-epithelialised more slowly (hazard ratio 0.47, 95% CI
      0.23 to 0.94). There was no significant difference in BSCVA or infiltrate/scar
      size at 3 weeks or 3 months. To have 80% power to detect a two-line difference in
      acuity, 360 cases would be required. CONCLUSIONS: Although corticosteroid
      treatment resulted in a statistically significant delay in re-epithelialisation,
      this did not translate to a significant difference in visual acuity,
      infiltrate/scar size or adverse events. To assess the effect of steroids on
      acuity, a larger trial is warranted and feasible.

PMID- 18829632
TI  - The role of Humphrey Matrix testing in the early diagnosis of retinopathy in type
      1 diabetes.
AB  - AIM: The aim of the study was to investigate the role of Humphrey Matrix
      threshold testing in the detection of early functional retinal impairment in
      subjects with type 1 diabetes mellitus (DM1) without any signs of retinal
      vasculopathy, and to investigate the relationship between both functional and
      structural retinal parameters and metabolic control. METHODS: Thirty eyes of 30
      subjects with DM1, with no sign of retinal vasculopathy, and 30 eyes of 30 age-
      and sex-matched healthy subjects were enrolled in this cross-sectional clinical
      study. Functional testing included Humphrey Matrix perimetry and white-on-white
      Humphrey visual field perimetry (HFA), while retinal nerve fibre layer (RNFL)
      thickness was measured by scanning laser polarimetry with variable corneal
      birefringence compensator (GDx VCC). RESULTS: Matrix mean deviation (MD) was
      found to be significantly reduced in subjects with DM1 compared with controls (
      1.10 (SD 2.98; 95% CI -2.21 to 0.01) vs 1.37 (SD 2.11; 95% CI 0.58 to 2.16), p =
      0.0005). HFA MD and pattern standard deviation (PSD) were significantly worse in
      subjects with DM1 compared with controls (p = 0.010 and p = 0.013 respectively).
      Among structural parameters, average peripapillary RNFL thickness was reduced in
      DM1 subjects (p = 0.006). Matrix MD and HFA MD and PSD, and average peripapillary
      and superior RNFL, were significantly reduced in subjects with DM1 with HbA(1c) >
      or = 7% compared with controls. CONCLUSIONS: Functional and structural retinal
      testing by Humphrey Matrix and GDx VCC could be useful for the identification of
      early retinal impairment in people with DM1 with no sign of retinal vasculopathy.

PMID- 18829633
TI  - Treatment of chronic ocular hypotony with intraocular application of sodium
      hyaluronate.
AB  - AIM: The aim of the study was to report the functional and morphological outcome
      of intraocular injection of sodium hyaluronate for treatment of chronic ocular
      hypotony (COH). METHODS: We reviewed the digital chart records of patients with
      COH who had received one or more injections of intravitreal or intracameral
      sodium hyaluronate (1.4% or 2.3%). The changes in the best corrected visual
      acuity (BCVA) and intraocular pressure (IOP) after treatment were recorded.
      RESULTS: Thirty-two eyes of 32 patients with a mean age of 56.8 years were
      analysed. Previous vitreoretinal surgery had been performed on all eyes for
      either ocular-penetrating trauma (six eyes), chronic uveitis (six eyes), full
      macular translocation (five eyes) or retinal detachment (15 eyes). Mean follow-up
      time after the first intraocular injection was 29.7 months. BCVA (logMAR) at the
      baseline and the last follow-up visit were 1.84 (SE 0.65) and 1.82 (SE 0.72),
      respectively (p = 0.87). The mean IOP at the baseline increased from 2.28 (SE
      0.27) mmHg to 7.12 (SE 1.03) mmHg at the last visit (p<0.001). At the final
      follow-up, 20 eyes (62.5%) had an IOP higher than 5 mmHg and 24 eyes (75%) had an
      unchanged or improved BCVA. CONCLUSIONS: Stabilisation of the IOP and vision in
      some eyes with COH following vitreoretinal surgery can be achieved with
      intraocular injection of sodium hyaluronate. Large case-series and long-term
      follow-up are necessary to confirm the beneficial role of intraocular sodium
      hyaluronate injections in such eyes.

PMID- 18829634
TI  - Hydroxychloroquine retinopathy screening.
AB  - AIM: To compare current hydroxychloroquine retinopathy screening practices with
      the published 2002 American Academy of Ophthalmology (AAO) Preferred Practice
      Patterns (PPP). METHODS: A multiple-choice survey was distributed to 105
      ophthalmologists to assess current screening practices and knowledge of patient
      risk factors. Results were compared with the PPP guidelines. A cost analysis of
      the PPP and survey paradigms was conducted. RESULTS: Sixty-seven (64%) of 105
      surveys were completed. The majority (90%) of physicians screen for
      hydroxychloroquine retinopathy with either central automated threshold perimetry
      or Amsler grid as recommended by the PPP. Most survey respondents could not
      correctly identify the evidence-based risk factors. The majority screen more
      frequently than recommended: 87% screen high-risk patients and 94% screen low
      risk patients more frequently than recommended in the PPP. The increased
      screening frequency of low-risk patients translates into an excess of $44 million
      in the first 5 years of therapy. If all patients were screened using exact PPP
      paradigm, savings could exceed $150 million every 10 years. CONCLUSIONS:
      Ophthalmologists currently screen for hydroxychloroquine retinopathy correctly;
      however, their lack of familiarity with evidence-based guidelines may result in
      excessive follow-up. Increasing awareness and implementation of the PPP could
      potentially reduce hydroxychloroquine retinopathy screening costs significantly.

PMID- 18829635
TI  - Near-infrared and short-wavelength autofluorescence imaging in central serous
      chorioretinopathy.
AB  - AIMS: The aim of the study was to compare the results of short-wavelength (SW)
      and near-infrared (NIR) autofluorescence (AF) in acute central serous
      chorioretinopathy (CSC). METHODS: Twenty-six eyes of the 26 patients diagnosed
      with CSC (mean age 37.4 years) were included in this retrospective study. AF
      images were evaluated and compared with angiographic and ophthalmoscopic
      findings. Fluorescein angiography and AF imaging were performed using a confocal
      scanning laser ophthalmoscope. RESULTS: Focally decreased AF at the leakage site
      was seen in most of the cases with acute CSC (20 of 26 eyes in SW-AF; 20 of 20
      eyes in NIR-AF). Twenty-four of the 26 cases had decreased SW-AF corresponding to
      the area of the serous retinal detachment, while 19 of the available 20 cases had
      decreased NIR-AF corresponding to the area of the serous retinal detachment.
      Increased granular AF corresponding to the extent of the former retinal
      detachment was seen earlier with SW-AF imaging, but disappeared later in the
      course of disease with NIR-AF imaging. CONCLUSIONS: AF imaging in CSC
      demonstrates different patterns according to the course of the disease,
      reflecting RPE and outer retinal changes. Combining two different methods of AF
      imaging could predict recent or former CSC episodes and may be a non-invasive
      technique for monitoring CSC and performing differential diagnosis.

PMID- 18829636
TI  - Tried and tested: the psychometric properties of the multiple sclerosis impact
      scale (MSIS-29) in a population-based study.
AB  - OBJECTIVE: To investigate the psychometric properties of the Multiple Sclerosis
      Impact Scale (MSIS-29) and to assess the relationship between the Kurtzke
      Expanded Disability Status Scale and the physical and psychological parts of this
      score. METHODS: A population-based study identified cases with definite multiple
      sclerosis (MS) in the north-east region of Ireland. They were examined and
      completed the MSIS-29. Cases were classified as mild (Expanded Disability Status
      Score (EDSS) 0-3.0), moderate (EDSS 3.5-5.5), or severe (6.0-9.5) MS. RESULTS:
      The 248 participants (82 male, 166 female) had a mean age of 49.1 years (SD
      12.4). EDSS ranged from 0 to 9.5 (median 6.0). Data quality was excellent (0.02%
      missing data), physical and psychological scores spanned the entire range with
      low floor and ceiling effects. Internal consistency was high (Cronbach's alpha
      0.97 - physical score, 0.93 - psychological score). The convergent validity of
      the physical impact score of the MSIS-29 with the Kurtzke EDSS was confirmed with
      a high Spearman's rank coefficient correlation of 0.63 (P = 0.01). Physical
      impact scores for mild, moderate, and severe disability as were statistically
      different at 25.9%, 48.0%, and 63.9%, respectively. Mean psychological score was
      non-significantly higher in the moderately disabled group at 47.4% compared with
      the severely disabled at 44.3% (P = 0.58). CONCLUSIONS: The MSIS-29 is an
      acceptable, reliable, and valid method of recording quality of life. A
      significant relationship between higher physical impact scores of the MSIS-29 and
      higher Kurtzke EDSS values suggests that is may be of use in clinical trials to
      monitor progression.

PMID- 18829637
TI  - Changes in CD4 count with antitubercular therapy in HIV infected children with
      tuberculosis.

PMID- 18829638
TI  - Safety, tolerability and effectiveness of generic HAART in HIV-infected children
      in South India.
AB  - HIV-infected children in resource-limited settings are increasingly gaining
      greater access to highly active antiretroviral therapy (HAART) but documented
      longitudinal data remains limited. We aimed to study the clinical and
      immunological outcomes among 67 South Indian HIV-infected children with >18
      months of follow-up on HAART at a tertiary HIV care program. The median CD4 cell
      count at enrolment was 290 cells microl(-1) and at treatment initiation was 225
      cells microl(-1). Patients demonstrated a significant rise in their CD4 cell
      counts between treatment initiation and after 6 months (701 cells microll(-1); p
      = 0.007), 12 months (741 cells microl(-1); p = 0.037), and 18 months of therapy
      (718 cells microl(-1); p = 0.005). The most common adverse events to therapy were
      nausea (20.9%) and rash (25.4%). Over one-fifth of patients (25.4%) substituted
      therapy due to toxicities and 19.4% of patients switched to second-line protease
      inhibitor-containing regimens. In this South Indian pediatric cohort, generic
      HAART was safe, effective and relatively well tolerated.

PMID- 18829639
TI  - Early detection of chronic kidney disease.

PMID- 18829641
TI  - Acute medical units reduce deaths and stay in hospital, studies show.

PMID- 18829642
TI  - Treatment of seizures in babies is hampered by lack of EEG equipment.

PMID- 18829640
TI  - Improving generalist end of life care: national consultation with practitioners,
      commissioners, academics, and service user groups.
AB  - OBJECTIVE: To identify major concerns of national and local importance in the
      provision, commissioning, research, and use of generalist end of life care.
      DESIGN: A national consultation and prioritising exercise using a modified form
      of the nominal group technique. PARTICIPANTS: Healthcare practitioners,
      commissioners, academics, and representatives of user and voluntary groups.
      SETTING: Primary and secondary care, specialist palliative care, and academic and
      voluntary sectors in England and Scotland. RESULTS: 74% of those invited
      (210/285) participated. The stage of life to which "end of life care" referred
      was not understood in a uniform way. Perceptions ranged from a period of more
      than a year to the last few days of life. Prominent concerns included
      difficulties in prognosis and the availability of adequate support for patients
      with advanced non-malignant disease. Generalists in both primary and secondary
      care were usually caring for only a few patients approaching the end of life at
      any one time at a point in time. It was therefore challenging to maintain skills
      and expertise particularly as educational opportunities were often limited. End
      of life care took place among many other competing and incentivised activities
      for general practitioners in the community. More needs to be known about models
      of end of life care and how these can be integrated in a generalist's workload. A
      greater evidence base is needed about the effectiveness and application of
      current tools such as the gold standards framework and Liverpool care pathway and
      about models of palliation in patients with diseases other than cancer.
      CONCLUSIONS: Definitions of end of life care need clarification and
      standardisation. A greater evidence base is needed to define models of good
      practice together with a commitment to provide education and training and
      adequate resources for service provision. More needs to be known about the
      context of provision and the influence of competing priorities and incentives.

PMID- 18829643
TI  - Papers show how tobacco companies stopped airline's smoking ban.

PMID- 18829644
TI  - China's tainted milk scandal spreads around world.

PMID- 18829645
TI  - Milan's appeals court is asked to rule on woman who has been in vegetative state
      for 16 years.

PMID- 18829647
TI  - UK introduces picture warnings on cigarette packets.

PMID- 18829651
TI  - Sleep disordered breathing in a 4 year old child with Down's syndrome.

PMID- 18829652
TI  - Tired and anxious.

PMID- 18829656
TI  - Beware of transfusions and hyperhaemolysis.

PMID- 18829657
TI  - Malarial chemoprophylaxis.

PMID- 18829658
TI  - Palliative care.

PMID- 18829659
TI  - Primary or secondary care?

PMID- 18829660
TI  - Simplifying consent for publication of case reports.

PMID- 18829661
TI  - Editors and authors vexed and confused by consent.

PMID- 18829662
TI  - What happens to papers rejected by the BMJ on ethical grounds.

PMID- 18829663
TI  - Truly independent research is impossible.

PMID- 18829665
TI  - Cognitive impairment in Gdi1-deficient mice is associated with altered synaptic
      vesicle pools and short-term synaptic plasticity, and can be corrected by
      appropriate learning training.
AB  - The GDI1 gene, responsible in human for X-linked non-specific mental retardation,
      encodes alphaGDI, a regulatory protein common to all GTPases of the Rab family.
      Its alteration, leading to membrane accumulation of different Rab GTPases, may
      affect multiple steps in neuronal intracellular traffic. Using electron
      microscopy and electrophysiology, we now report that lack of alphaGDI impairs
      several steps in synaptic vesicle (SV) biogenesis and recycling in the
      hippocampus. Alteration of the SV reserve pool (RP) and a 50% reduction in the
      total number of SV in adult synapses may be dependent on a defective endosomal
      dependent recycling and may lead to the observed alterations in short-term
      plasticity. As predicted by the synaptic characteristics of the mutant mice, the
      short-term memory deficit, observed when using fear-conditioning protocols with
      short intervals between trials, disappeared when the Gdi1 mutants were allowed to
      have longer intervals between sessions. Likewise, previously observed deficits in
      radial maze learning could be corrected by providing less challenging pre
      training. This implies that an intact RP of SVs is necessary for memory
      processing under challenging conditions in mice. The possibility to correct the
      learning deficit in mice may have clinical implication for future studies in
      human.

PMID- 18829666
TI  - Deletion of smn-1, the Caenorhabditis elegans ortholog of the spinal muscular
      atrophy gene, results in locomotor dysfunction and reduced lifespan.
AB  - Spinal muscular atrophy is the most common genetic cause of infant mortality and
      is characterized by degeneration of lower motor neurons leading to muscle
      wasting. The causative gene has been identified as survival motor neuron (SMN).
      The invertebrate model organism Caenorhabditis elegans contains smn-1, the
      ortholog of human SMN. Caenorhabditis elegans smn-1 is expressed in various
      tissues including the nervous system and body wall muscle, and knockdown of smn-1
      by RNA interference is embryonic lethal. Here we show that the smn-1(ok355)
      deletion, which removes most of smn-1 including the translation start site,
      produces a pleiotropic phenotype including late larval arrest, reduced lifespan,
      sterility as well as impaired locomotion and pharyngeal activity. Mutant
      nematodes develop to late larval stages due to maternal contribution of the smn-1
      gene product that allows to study SMN-1 functions beyond embryogenesis. Neuronal,
      but not muscle-directed, expression of smn-1 partially rescues the smn-1(ok355)
      phenotype. Thus, the deletion mutant smn-1(ok355) provides a useful platform for
      functional analysis of an invertebrate ortholog of the human SMN protein.

PMID- 18829671
TI  - The role of neutropenia on outcomes of cancer patients with community-acquired
      pneumonia.
AB  - Although the presence of neutropenia may predispose cancer patients to develop
      community-acquired pneumonia, the role of neutropenia on their outcomes has not
      been investigated. The purpose of the present study was to compare clinical
      outcomes of cancer community-acquired pneumonia patients with and without
      neutropenia. Patients with cancer, identified in the Community-Acquired Pneumonia
      Organization database, were divided into two groups according to the type of
      cancer and the presence of neutropenia: patients with solid cancer without
      neutropenia versus those with functional or absolute neutropenia. Among the 3,106
      community-acquired pneumonia patients enrolled, 135 had cancer without
      neutropenia and 75 had cancer with neutropenia. No significant difference was
      found between patients with and without neutropenia regarding mean time to
      clinical stability (5.4+/-2.7 versus 4.9+/-2.7 days, respectively), mean length
      of hospital stay (9.2+/-7.7 versus 9.9+/-9.6 days) and in-hospital mortality (18
      versus 15%, respectively). Using a multiple logistic regression model,
      neutropenia was not associated with mortality in cancer patients when adjusting
      for significant covariates (odds ratio 1.30). Lack of neutropenia, during the
      initial evaluation of a cancer community-acquired pneumonia patient, should not
      be considered an indicator of better clinical outcome.

PMID- 18829672
TI  - Clinical course and lung function change of idiopathic nonspecific interstitial
      pneumonia.
AB  - Most studies of idiopathic nonspecific interstitial pneumonia (NSIP) have
      primarily studied mortality. In order to clarify the detailed outcome and
      prognostic markers in idiopathic NSIP, the clinical course with initial
      radiological and clinical features was analysed. The clinical course of 83
      patients who were classified with idiopathic NSIP (72 fibrotic, 11 cellular; 27
      males and 56 females; mean+/-sd age 54.4+/-10.1 yrs) was retrospectively
      analysed. In fibrotic NSIP, 16 (22%) patients died of NSIP-related causes with a
      median (range) follow-up of 53 (0.3-181) months. Despite the favourable survival
      (5-yr 74%), patients with fibrotic NSIP were frequently hospitalised with
      recurrence rate of 36%. Reduced forced vital capacity at 12 months was a
      predictor of mortality. On follow-up, lung function was improved or stable in
      approximately 80% of the patients. The extent of consolidation and ground-glass
      opacity on initial high-resolution computed tomography correlated significantly
      with serial changes of lung function, and the presence of honeycombing was a
      predictor of poor prognosis. During follow-up, eight (10%) patients developed
      collagen vascular disease. In conclusion, the overall prognosis of fibrotic
      nonspecific interstitial pneumonia was good; however, there were significant
      recurrences despite initial improvement and a subset of the patients did not
      respond to therapy. Some patients developed collagen vascular diseases at a later
      date.

PMID- 18829673
TI  - Dietary patterns and asthma in the E3N study.
AB  - The aim of the present study was to determine dietary patterns and investigate
      their association with asthma incidence, current asthma and frequent asthma
      exacerbations. Dietary habits and asthma data were collected from the large E3N
      study (of French females, mostly teachers). Of the 54,672 females followed-up in
      2003, 2,634 reported ever-adulthood asthma, 1,063 reported current asthma, 206
      reported frequent asthma attacks (one or more a week), and 628 reported asthma
      onset between 1993 and 2003. Using principal component analysis, three dietary
      patterns were identified: the "prudent" pattern (fruits and vegetables); the
      "Western" pattern (pizza/salty pies, dessert and cured meats); and the "nuts and
      wine" pattern. Pattern scores were categorised into tertiles, and the incidence
      and prevalence of asthma was compared between tertiles. After adjustment for
      confounders, no association of dietary patterns was observed with asthma
      incidence, ever-asthma or current asthma. The Western pattern was associated with
      an increased risk of reporting frequent asthma attacks (highest versus lowest
      tertile odds ratio (OR) 1.79, 95% confidence interval (CI) 1.11-3.73). Increasing
      scores of the nuts and wine pattern were associated with a decreased risk of
      reporting frequent asthma attacks (highest versus lowest tertile OR 0.65, 95% CI
      0.31-0.96). The results of the present study suggest that overall diet could be
      involved in frequent asthma exacerbations, one aspect of asthma severity.

PMID- 18829674
TI  - Assessing response to treatment of exacerbations of bronchiectasis in adults.
AB  - The present study aimed to assess the effect of intravenous antibiotic therapy on
      clinical and laboratory end-points in exacerbations of noncystic fibrosis
      bronchiectasis and to determine whether the outcomes were influenced by the
      pathogenic organism isolated. A prospective cohort study was conducted from
      November 2006 to March 2008 of exacerbations requiring intravenous antibiotics.
      End-points included 24-h sputum volume, forced expiratory volume in one second
      (FEV(1)), forced vital capacity (FVC), incremental shuttle walk test, qualitative
      sputum microbiology, white cell count, erythrocyte sedimentation rate, C-reactive
      protein (CRP) and St George's Respiratory Questionnaire (SGRQ). Exacerbations due
      to Pseudomonas aeruginosa were compared with exacerbations due to other potential
      pathogenic organisms. In total, 32 exacerbations were studied. Following 14 days
      of intravenous antibiotics, all outcomes significantly improved independent of a
      pathogenic organism, except FEV(1) and FVC. The most responsive markers were: 24
      h sputum volume (reduced in all patients and 80% had >/=50% reduction); sputum
      bacterial clearance (78.1%); CRP (>/=75% reduction in 62.5%) and SGRQ (>/=4 unit
      improvement in 89.7%). CRP, 24-h sputum volume and SGRQ improved independent of
      microbial clearance. In the current study, 24-h sputum volume, microbial
      clearance, C-reactive protein and St George's Respiratory Questionnaire were the
      most useful parameters to assess response to treatment of exacerbations of
      bronchiectasis. Outcomes were similar independent of the pathogenic organism with
      the exception of forced expiratory volume in one second and forced vital
      capacity.

PMID- 18829675
TI  - Computed tomographic emphysema distribution: relationship to clinical features in
      a cohort of smokers.
AB  - Computed tomography (CT) scanning allows precise assessment of both the extent
      and distribution of emphysema. There has been little work on the relationship
      between the distribution of emphysema and clinical features of the disease. The
      current study investigated the association between clinical features and
      distribution of emphysema. A total of 129 patients with smoking-related chronic
      obstructive pulmonary disease underwent CT assessment of the extent and
      distribution of their emphysema (core/rind and upper/lower zone predominance).
      Emphysema was found predominantly in the upper/core zone and this distribution
      was related to the extent of disease. Core predominance was associated with lower
      forced expiratory volume in one second (FEV(1)), FEV(1)/forced vital capacity
      ratio and body mass index (BMI); and with higher BODE (BMI, airflow obstruction,
      dyspnoea and exercise capacity) index and Medical Research Council dyspnoea
      score. Upper-zone predominance was associated with female sex and an increased
      total St George's Respiratory Questionnaire score. Using multiple linear
      regression age, sex and whole lung emphysema severity were independently
      associated with core/rind distribution, while sex and whole lung emphysema
      severity were independently related to upper/lower distribution. Distribution of
      emphysema related best to clinical features when divided into core/rind
      predominance. However, the effects were not independent of the extent of
      emphysema. Increased age and female sex were related to disease distribution
      independent of emphysema severity. These findings may be related to differences
      in development of emphysema.

PMID- 18829676
TI  - Recurrence of tuberculosis in a low-incidence setting.
AB  - Recurrence of active tuberculosis following treatment of an initial disease
      episode can occur due to endogenous re-activation or exogenous re-infection.
      Cases of recurrent tuberculosis in the Australian state of New South Wales
      between 1994 and 2006 were identified by data linkage analysis with confirmatory
      review of case notes. Patients with more than one culture-positive disease
      episode during that time period who had completed treatment for the initial
      disease episode were included. Genotyping of Mycobacterium tuberculosis was used
      to determine whether recurrence was likely to be due to re-activation or re
      infection. There were 5,723 tuberculosis notifications between 1994 and 2006,
      3,731 of which were culture-positive. Fifteen (0.4%) patients had recurrent
      culture-positive disease over a mean 5.7 yrs of follow-up (crude annual incidence
      71 per 100,000 population). Recurrent tuberculosis was attributable to re
      activation (indistinguishable strains) in 11 (73%) cases and to re-infection
      (different strains) in four (27%). In a low-incidence setting of tuberculosis, a
      control programme incorporating directly observed therapy for active disease
      resulted in a very low rate of recurrent tuberculosis over a long period of
      follow-up. Re-infection is less likely than re-activation, but still contributes
      significantly to the number of cases with recurrent disease.

PMID- 18829677
TI  - Stimulation of acetylcholine receptors impairs host defence during pneumococcal
      pneumonia.
AB  - The cholinergic nervous system can inhibit the systemic inflammation accompanying
      sepsis by virtue of a specific action of acetylcholine on alpha7 cholinergic
      receptors. The current authors sought to determine the effect of nicotine, an
      alpha7 cholinergic receptor agonist, on the host response to pneumonia caused by
      Streptococcus pneumoniae. Mice were intranasally infected with S. pneumoniae and
      treated with nicotine or saline intraperitoneally using a treatment schedule
      shown to improve host defence against abdominal sepsis. Nicotine treatment was
      associated with a transiently enhanced growth of S. pneumoniae, as indicated by
      higher bacterial loads in both lungs and blood at 24 h after infection. At 48 h
      after infection, bacterial burdens had increased in both treatment groups and
      differences were no longer present. Remarkably, mice treated with nicotine showed
      enhanced lung inflammation at 24 h after infection. Moreover, both lung and
      plasma concentrations of the pro-inflammatory cytokines tumour necrosis factor
      alpha and interferon-gamma were higher in nicotine-treated animals at this time
      point. Additional studies examining the effect of nicotine on the immediate (4-h)
      inflammatory response to S. pneumoniae did not reveal an anti-inflammatory effect
      of nicotine either. The present data suggest that nicotine transiently impairs
      host defence in pneumococcal pneumonia.

PMID- 18829678
TI  - Neural respiratory drive in healthy subjects and in COPD.
AB  - The aim of the present study was to use the diaphragm electromyogram (EMG(di)) to
      compare levels of neural respiratory drive (NRD) in a cohort of healthy subjects
      and chronic obstructive pulmonary disease (COPD) patients, and to investigate the
      relationship between NRD and pulmonary function in COPD. EMG(di) was recorded at
      rest and normalised to peak EMG(di) recorded during maximum inspiratory
      manoeuvres (EMG(di) % max) in 100 healthy subjects and 30 patients with COPD,
      using a multipair oesophageal electrode. EMG(di) was normalised to the amplitude
      of the diaphragm compound muscle action potential (CMAP(di,MS)) in 64 healthy
      subjects. The mean+/-sd EMG(di) % max was 9.0+/-3.4% in healthy subjects and
      27.9+/-9.9% in COPD patients, and correlated with percentage predicted forced
      expiratory volume in one second, vital capacity and inspiratory capacity in
      patients. EMG(di) % max was higher in healthy subjects aged 51-80 yrs than in
      those aged 18-50 yrs (11.4+/-3.4 versus 8.2+/-2.9%, respectively). Observations
      in the healthy group were similar when peak EMG(di) or CMAP(di,MS) were used to
      normalise EMG(di). Levels of neural respiratory drive were higher in chronic
      obstructive pulmonary disease patients than healthy subjects, and related to
      disease severity. Diaphragm compound muscle action potential could be used to
      normalise diaphragm electromyogram if volitional inspiratory manoeuvres could not
      be performed, allowing translation of the technique to critically ill and
      ventilated patients.

PMID- 18829679
TI  - Prognostic and aetiological factors in chronic thromboembolic pulmonary
      hypertension.
AB  - Several prognostic variables have previously been identified in patients with
      chronic thromboembolic pulmonary hypertension (CTEPH). Specific medical
      conditions have also been associated with the development and prognosis of CTEPH.
      Using a national registry, the current authors have assessed the prognostic value
      of a larger number of variables and have also attempted to validate the clinical
      importance of previously identified aetiological factors. Baseline information
      for all 469 CTEPH patients diagnosed in the UK pulmonary hypertension service
      between January 2001 and June 2006 was collected from hospital records. Although
      univariate analysis confirmed the prognostic importance of pulmonary resistance,
      in multivariate analysis gas transfer and exercise capacity predicted pulmonary
      endarterectomy perioperative mortality. Cardiac index and exercise capacity
      independently predicted outcome in patients with nonoperable disease. Previous
      splenectomy was noted in 6.7% of patients, being significantly more common in
      patients with nonoperable than operable disease (13.7 versus 3.6%). Medical risk
      factors were not found to predict mortality. In a large national cohort,
      predictors of outcome in patients with both operable and nonoperable chronic
      thromboembolic pulmonary hypertension have been identified. These may be useful
      in planning treatment. The aetiological importance of previously identified
      medical risk factors has been confirmed, although the current authors were unable
      to validate their prognostic strength.

PMID- 18829680
TI  - Mechanisms of heteroresistance to isoniazid and rifampin of Mycobacterium
      tuberculosis in Tashkent, Uzbekistan.
AB  - Heteroresistance of Mycobacterium tuberculosis (MTB) is defined as the
      coexistence of susceptible and resistant organisms to anti-tuberculosis (TB)
      drugs in the same patient. Heteroresistance of MTB is considered a preliminary
      stage to full resistance. To date, no mechanism causing heteroresistance of MTB
      has been proven. Clinical specimens and cultures from 35 TB patients from
      Tashkent, Uzbekistan, were analysed using the Genotype MTBDR assay (Hain
      Lifescience, Nehren, Germany), which is designed to detect genetic mutations
      associated with resistance to rifampin and isoniazid. Cases of heteroresistance
      were further subjected to genotyping using mycobacterial interspersed repetitive
      unit-variable-number tandem repeat typing, spoligotyping and IS6110
      fingerprinting. Heteroresistance to rifampin and/or isoniazid was found in seven
      cases (20%). In five of them, heteroresistance was caused by two different
      strains and in two by a single strain of the Beijing genotype. The latter cases
      had a history of relapse of their TB. For the first time, two different
      mechanisms of heteroresistance in tuberculosis have been proven using a stepwise
      molecular-biological approach: 1) superinfection with two different strains,
      which is of interest for clinical infection control practitioners; and 2)
      splitting of a single strain into susceptible and resistant organisms. The latter
      mechanism is most likely to be related to poor treatment quality and could serve
      as a quality marker for tuberculosis therapy programmes in the future.

PMID- 18829681
TI  - Reciprocal regulation of iNOS and PARP-1 during allergen-induced eosinophilia.
AB  - Inducible nitric oxide synthase (iNOS) inhibition was recently shown to exert no
      effect on allergen challenge in human asthma, raising serious concerns about the
      role of the protein in the disease. The present study investigated the role of
      iNOS in ovalbumin-induced eosinophilia from the perspective of its relationship
      with poly(ADP-ribose) polymerase-1 (PARP-1) and oxidative DNA damage. A mouse
      model of ovalbumin-induced eosinophilia was used to conduct the studies. iNOS
      associated protein nitration and tissue damage were partially responsible for
      allergen-induced eosinophilia. iNOS expression was required for oxidative DNA
      damage and PARP-1 activation upon allergen challenge. PARP-1 was required for
      iNOS expression and protein nitration, and this requirement was connected to
      nuclear factor-kappaB. PARP-1 was an important substrate for iNOS-associated by
      products after ovalbumin-challenge. PARP-1 nitration blocked its poly(ADP
      ribosyl)ation activity. Interleukin-5 re-establishment in ovalbumin-exposed PARP
      1(-/-) mice reversed eosinophilia and partial mucus production without a reversal
      of iNOS expression, concomitant protein nitration or associated DNA damage. The
      present results demonstrate a reciprocal relationship between inducible nitric
      oxide synthase and poly(ADP-ribose) polymerase-1 and suggest that expression of
      inducible nitric oxide synthase may be dispensable for eosinophilia after
      interleukin-5 production. Inducible nitric oxide synthase may be required for
      oxidative DNA damage and full manifestation of mucus production. Such
      dispensability may explain, in part, the reported ineffectiveness of inducible
      nitric oxide synthase inhibition in preventing allergen-induced inflammation in
      humans.

PMID- 18829682
TI  - MMP expression and abnormal lung permeability are important determinants of
      outcome in IPF.
AB  - Matrix metalloproteinases (MMPs) degrade all of the extracellular matrix
      components of the intersititium and may play a role in abnormal alveolar
      permeability, which is a feature of idiopathic pulmonary fibrosis (IPF). The aims
      of the present study were to evaluate MMP protein levels in patients with IPF and
      determine any relationship to treatment and markers of permeability. In total, 20
      patients with IPF and eight normal controls underwent bronchoalveolar lavage.
      MMP, tissue inhibitor of metalloproteinase, and vascular endothelial growth
      factor (VEGF) levels were related to clinical outcome and protein permeability
      index. MMP-3, -7, -8 and -9 were elevated in IPF lavage fluid and levels remained
      high despite treatment. Levels of MMP-3, -7, -8 and -9, VEGF and protein
      permeability index were higher in those who died early during follow-up. VEGF,
      and MMP-8 and -9 levels were higher in those with a rapidly declining lung
      function over 1 yr. Levels of MMP-3, -7, -8 and -9 correlated with an increased
      permeability index. Matrix metalloproteinase levels were elevated in idiopathic
      pulmonary fibrosis patients and were not modulated by current standard treatment.
      Matrix metalloproteinase production through an interaction with the known
      vascular permogen, vascular endothelial growth factor, was potentially associated
      with abnormal capillary permeability and may have potentiated the neo
      angiogenesis seen in idiopathic pulmonary fibrosis. The changes were greatest in
      those who died or progressed during follow-up, suggesting that drugs targeting
      vascular endothelial growth factor or matrix metalloproteinase activity warrant
      assessment as novel therapy for idiopathic pulmonary fibrosis.

PMID- 18829683
TI  - Cysteinyl leukotriene receptor 1 gene variation and risk of asthma.
AB  - Although it has been recognised that genetics plays an important role in the
      development of asthma, important causal loci remain to be identified. The aim of
      the present study was to examine the association of known and novel candidate
      genes with asthma. Two independent samples, including 170 asthmatic cases and 347
      controls in the initial sample, and 202 asthmatic cases and 332 controls in the
      confirmation sample, were recruited from the same region of China. Functional
      single nucleotide polymorphisms (SNPs; n = 129) from 105 genes were genotyped
      using MassARRAY technology, and 119 SNPs were used for the subsequent analysis.
      In the initial sample, three SNPs, rs320995 in the cysteinyl leukotriene receptor
      1 gene, rs1047266 in the tumour necrosis factor receptor superfamily, member 10b,
      gene and rs40401 in the interleukin-3 gene, were associated with risk of asthma.
      Notably, under the recessive genetic model, subjects without the thymidine allele
      in SNP rs320995 had a 3.1 times higher risk of asthma, which remained significant
      after accounting for multiple testing. This association was replicated in the
      confirmation sample and validated by meta-analysis. Further, sex-specific
      analysis was performed, but no sex difference was found. The present study
      provided coherent evidence that cysteinyl leukotriene receptor 1 gene variation
      is associated with risk of asthma.

PMID- 18829684
TI  - STOPP (Screening Tool of Older Persons' potentially inappropriate Prescriptions):
      application to acutely ill elderly patients and comparison with Beers' criteria.
AB  - INTRODUCTION: STOPP (Screening Tool of Older Persons' potentially inappropriate
      Prescriptions) is a new, systems-defined medicine review tool. We compared the
      performance of STOPP to that of established Beers' criteria in detecting
      potentially inappropriate medicines (PIMs) and related adverse drug events (ADEs)
      in older patients presenting for hospital admission. METHODS: we prospectively
      studied 715 consecutive acute admissions to a university teaching hospital.
      Diagnoses, reason for admission and concurrent medications were recorded. STOPP
      and Beers' criteria were applied. PIMs with clear causal connection or
      contribution to the principal reason for admission were determined. RESULTS:
      median patient age (interquartile range) was 77 (72-82) years. Median number of
      prescription medicines was 6 (range 0-21). STOPP identified 336 PIMs affecting
      247 patients (35%), of whom one-third (n = 82) presented with an associated ADE.
      Beers' criteria identified 226 PIMs affecting 177 patients (25%), of whom 43
      presented with an associated ADE. STOPP-related PIMs contributed to 11.5% of all
      admissions. Beers' criteria-related PIMs contributed to significantly fewer
      admissions (6%). CONCLUSION: STOPP criteria identified a significantly higher
      proportion of patients requiring hospitalisation as a result of PIM-related
      adverse events than Beers' criteria. This finding has significant implications
      for hospital geriatric practice.

PMID- 18829685
TI  - Emergency room geriatric assessment--urgent, important or both?

PMID- 18829686
TI  - Trends in hospital inpatient episodes for signs, symptoms and ill-defined
      conditions.

PMID- 18829687
TI  - Care home medicine in the UK--in from the cold.
AB  - The quality of care within care homes comes under frequent media scrutiny, and is
      underpinned by the medical support to the staff. In the UK, medical care to care
      homes is provided by general practitioners. A GP is likely to have patients in
      many homes, and each home relates to many GPs. The growing complexity of patients
      in care requires proactive models of care delivered by those with an
      understanding of care home medicine. A range of innovative models of medical care
      are emerging across the UK which have the potential to improve the standard of
      care in homes, and reduce inappropriate use of secondary care admissions. These
      models are described, and the need for them to be subjected to evaluation.

PMID- 18829688
TI  - The geriatric day hospital: past, present and future.

PMID- 18829689
TI  - The Winchester falls project: a randomised controlled trial of secondary
      prevention of falls in older people.
AB  - BACKGROUND: the mortality and morbidity of falls in older people is significant,
      with recurrent fallers being at an increased risk. The most effective way to
      reduce falls in this group is not clear. OBJECTIVE: to determine the
      effectiveness of two interventions, one based in primary care and the other in
      secondary care, at preventing further falls in recurrent fallers. DESIGN: cluster
      randomised controlled trial. PARTICIPANTS: sixty-five years or over, living in
      the community, two or more falls in the previous year and not presenting to an
      emergency department with index fall. SETTING: Mid Hampshire, UK. INTERVENTION:
      eighteen general practices were randomly allocated to one of three groups. The
      primary care group was assessed by nurses in the community, using a risk factor
      review and subsequent targeted referral to other professionals. The secondary
      care group received a multi-disciplinary assessment in a day hospital followed by
      identified appropriate interventions. The control group received usual care.
      Follow-up was for 1 year. RESULTS: five hundred and five participants were
      recruited. Follow-up was completed in 83% (421/505). The proportion of
      participants who fell again was significantly lower in the secondary care group
      (75%, 158/210) compared to the control group [84%, 133/159, adjusted odds ratio
      (OR) 0.52 (95% CI 0.35-0.79) P = 0.002]. The primary care group showed similar
      results to the control group [87%, 118/136, adjusted OR 1.17 (95% CI 0.57-2.37) P
      = 0.673]. CONCLUSION: a structured multi-disciplinary assessment of recurrent
      fallers significantly reduced the number experiencing further falls, but a
      community-based nurse-led assessment with targeted referral to other
      professionals did not.

PMID- 18829690
TI  - Responsiveness of the Duke Social Support sub-scales in older women.
AB  - OBJECTIVE: an abbreviated form of the Duke Social Support Index (DSSI) as used in
      a large longitudinal study of older Australian women was examined with respect to
      factors that might be expected to affect social support for older women over
      time. METHODS: in this large cohort study two sub-scales of the DSSI, one
      describing the size and structure of the social network (four items) and the
      other perceiving satisfaction with social support (six items), were analysed in
      relation to outcome and exploratory variables. RESULTS: over a 3-year period, the
      network score increased among women whose life circumstances meant that they were
      likely to receive more support (e.g. recent widowhood). Likewise, those women at
      risk of becoming more socially isolated (e.g. those with sensory loss) became
      less satisfied with their social support. Changes in both measures were tempered
      by women's mental health and optimism. CONCLUSIONS: although the sub-scales of
      the DSSI may not fully reflect the complexity of social support paradigms, they
      are responsive to changes in the lives of older women and can be useful in
      community-based epidemiological studies.

PMID- 18829691
TI  - Detecting of chronic kidney disease in older people by the MDRD and MCQ formulas.

PMID- 18829692
TI  - Attenuated peripheral vasoconstriction during an orthostatic challenge in older
      men.
AB  - BACKGROUND: orthostatic hypotension is common in older men and associated with
      morbidity and mortality. During orthostatic challenges, older men maintain their
      blood pressure by an augmented increase in total peripheral resistance. Changes
      in the leg vascular bed contribute importantly to blood pressure regulation
      during orthostatic challenges, partly because of blood pooling in the legs.
      Little is known about the contribution of the leg vascular bed to the augmented
      increase in total peripheral resistance. OBJECTIVE: to examine tilt-induced
      peripheral vasoconstriction in the leg vascular bed of young and older men.
      METHODS: we measured forearm and calf blood flow in 12 young and 12 older men,
      using venous occlusion plethysmography during 30 degrees head-up tilt (HUT).
      Forearm and calf vascular resistance were calculated as mean arterial blood
      pressure divided by blood flow. RESULTS: during HUT, calf and forearm vascular
      resistance increased in older and young men. The increase in forearm vascular
      resistance was similar between older (40 +/- 6%) and young men (51 +/- 12%).
      However, the increase in calf vascular resistance was lower in older (96 +/- 15%)
      than in young men (175 +/- 30%). CONCLUSION: advancing age leads to an attenuated
      tilt-induced increase in calf vascular resistance, which may contribute to age
      related orthostatic hypotension.

PMID- 18829693
TI  - A systematic review and meta-analysis of studies using the STRATIFY tool for
      prediction of falls in hospital patients: how well does it work?
AB  - BACKGROUND: STRATIFY is a prediction tool developed for use in for hospital
      inpatients, using a 0-5 score to predict patients who will fall. It has been
      widely used as part of hospital fall prevention plans, but it is not clear how
      good its operational utility is in a variety of settings. OBJECTIVES: (i) to
      describe the predictive validity of STRATIFY for identifying hospital inpatients
      who will fall via systematic review and descriptive analysis, based on its use in
      several prospective cohort studies of hospital inpatients; (ii) to describe the
      predictive validity of STRATIFY among inpatients in geriatric rehabilitation via
      meta-analysis and (iii) in turn, to help practitioners and institutions wishing
      to implement interventions to prevent in-hospital falls. METHODS: a systematic
      literature review of prospective validation studies of STRATIFY for falls
      prediction in hospital inpatients. For inclusion, studies must report prospective
      validation cohorts, with sufficient data for calculation of sensitivity (SENS),
      specificity (SPEC), negative and positive predictive value (NPV and PPV), total
      predictive accuracy (TPA) and 95% confidence intervals (CI). We performed meta
      analysis using precision-weighted fixed- and random-effects models using studies
      that evaluated STRATIFY among geriatric rehabilitation inpatients. MEASUREMENTS:
      key features of the patient population, setting, study design and numbers of
      falls/fallers were abstracted. SENS, SPEC, PPV, NPV, TPA and 95% CI were reported
      for each cohort. Pooled values and chi-squared test for homogeneity were reported
      for a meta-analysis of studies conducted in geriatric rehabilitation settings.
      RESULTS: forty-one papers were identified by the search, with eight ultimately
      eligible for inclusion in the systematic review and four for inclusion in the
      meta-analysis. The predictive validity of STRATIFY, using a random-effects model,
      for the four studies involving geriatric patients was as follows: SENS 67.2 (95%
      CI 60.8, 73.6), SPEC 51.2 (95% CI 43.0, 59.3), PPV 23.1 (95% CI 14.9, 31.2), NPV
      86.5 (95% CI 78.4, 94.6). The Q((3)) test for homogeneity was not significant for
      SENS at P = 0.36, but it was significant at P < 0.01 for SPEC, PPV and NPV. TPA
      across all four studies varied from 43.2 to 60.0. CONCLUSION: the current study
      reveals a relatively high NPV and low PPV and TPA for the STRATIFY instrument,
      suggesting that it may not be optimal for identifying high-risk individuals for
      fall prevention. Further, the study demonstrates that population and setting
      affect STRATIFY performance.

PMID- 18829694
TI  - The influence of parental history of Alzheimer's disease and apolipoprotein E
      epsilon4 on the BOLD signal during recognition memory.
AB  - First-degree family history (FH) of sporadic Alzheimer's disease and the
      apolipoprotein E epsilon4 allele (APOE4) are risk factors for Alzheimer's disease
      that may affect brain function prior to onset of clinical symptoms. In this
      functional MRI (fMRI) study, we used an episodic recognition task that required
      discrimination of previously viewed (PV) and novel (NV) faces to examine
      differences in blood oxygen level dependent (BOLD) signal due to risk factors in
      74 middle-aged cognitively normal individuals. The group effects on this
      recognition task were tested with a 2 x 2 ANCOVA factorial design (+FH/-FH and
      +APOE4/-APOE4). There were significant APOE4 and FH effects in the left dorsal
      posterior cingulate cortex and precuneus, where decreased risk resulted in
      greater activity during recollection. Recognition performance was positively
      correlated with BOLD signal in the left posterior hippocampus, parahippocampal
      retrosplenial gyrus and left superior frontal cortex regardless of risk factors.
      To examine condition-specific group effects, both the PV and NV faces were tested
      further in separate 2 x 2 ANCOVAs. Both models revealed an APOE effect, with the 
      APOE4 group showing stronger signal than the +APOE4 group in anterior cingulate
      cortices, while a FH effect was found in the dorsal cuneus and medial frontal
      cortices with the -FH group showing stronger signal than the +FH group. Finally,
      interactions between APOE4 and FH effects were found bilaterally in the fusiform
      gyrus. These results suggest that risk factors and cognitive performance each
      influence brain activity during recognition. The findings lend further support to
      the idea that functional brain changes may begin far in advance of symptomatic
      Alzheimer's disease.

PMID- 18829696
TI  - Hypothalamic involvement in Huntington's disease: an in vivo PET study.
AB  - Recent studies have shown alterations in metabolism, sleep and circadian rhythms
      as well as in several neuropeptides derived from the hypothalamic-pituitary axis
      in Huntington's disease patients; however, the pathology underlying these
      abnormalities is not known. Our aim was to assess in vivo D(2) receptor's
      loss/dysfunction and increases in microglial activation in the hypothalamus of
      symptomatic Huntington's disease patients and premanifest Huntington's disease
      gene carriers using PET with (11)C-raclopride (RAC), a specific D(2) receptor
      ligand and (11)C-(R)-PK11195 (PK), a marker of microglial activation. We have
      studied 9 symptomatic Huntington's disease patients (age = 46.8 +/- 4.7 years;
      mean +/- SD) and 10 premanifest Huntington's disease gene carriers (age = 41.9 +/
      8.2 years; mean +/- SD). RAC and PK findings for these subjects were compared
      with those of a group of normal controls (RAC, n = 9; PK, n = 10). In the
      symptomatic Huntington's disease group, we found a significant decrease (P =
      0.0012) in mean hypothalamic RAC binding potential (BP) and a significant
      increase in mean hypothalamic PK BP (P = 0.0008). Similarly, a significant
      decrease (P = 0.0143) in mean hypothalamic RAC BP and a significant increase in
      mean hypothalamic PK BP (P = 0.0057) were observed in the premanifest
      Huntington's disease group. Hypothalamic RAC and PK BP values correlated with
      each other in combined Huntington's disease groups (r = -0.6180, P = 0.0048) but
      not with striatal RAC and PK BP values. Our data demonstrate, for the first time,
      significant D(2) receptor loss and microglia activation in the hypothalamus of
      Huntington's disease. These pathological changes occur very early in the course
      of the disease and may partly explain the development of commonly reported
      symptoms in Huntington's disease including progressive weight loss, alterations
      in sexual behaviour and disturbances in the wake-sleep cycle.

PMID- 18829695
TI  - Functional variants of the dopamine receptor D2 gene modulate prefronto-striatal
      phenotypes in schizophrenia.
AB  - Dopamine D2 receptor signalling is strongly implicated in the aetiology of
      schizophrenia. We have recently characterized the function of three DRD2 SNPs:
      rs12364283 in the promoter affecting total D2 mRNA expression; rs2283265 and
      rs1076560, respectively in introns 5 and 6, shifting mRNA splicing to two
      functionally distinct isoforms, the short form of D2 (D2S) and the long form
      (D2L). These two isoforms differentially contribute to dopamine signalling in
      prefrontal cortex and in striatum. We performed a case-control study to determine
      association of these variants and of their main haplotypes with several
      schizophrenia-related phenotypes. We demonstrate that the minor allele in the
      intronic variants is associated with reduced expression of %D2S of total mRNA in
      post-mortem prefrontal cortex, and with impaired working memory behavioural
      performance, both in patients and controls. However, the fMRI results show
      opposite effects in patients compared with controls: enhanced engagement of
      prefronto-striatal pathways in controls and reduced activity in patients.
      Moreover, the promoter variant is also associated with working memory activity in
      prefrontal cortex and striatum of patients, and less robustly with negative
      symptoms scores. Main haplotypes formed by the three DRD2 variants showed
      significant associations with these phenotypes consistent with those of the
      individual SNPs. Our results indicate that the three functional DRD2 variants
      modulate schizophrenia phenotypes possibly by modifying D2S/D2L ratios in the
      context of different total D2 density.

PMID- 18829697
TI  - Confabulation in Alzheimer's disease: poor encoding and retrieval of over-learned
      information.
AB  - Patients who confabulate retrieve personal habits, repeated events or over
      learned information and mistake them for actually experienced, specific unique
      events. Although some hypotheses favour a disruption of frontal/executive
      functions operating at retrieval, the respective involvement of encoding and
      retrieval processes in confabulation is still controversial. The present study
      sought to investigate experimentally the involvement of encoding and retrieval
      processes and the interference of over-learned information in the confabulation
      of Alzheimer's disease patients. Twenty Alzheimer's disease patients and 20
      normal controls encoded and retrieved unknown stories, well-known fairy tales
      (e.g. Snow White) and modified well-known fairy tales (e.g. Little Red Riding
      Hood is not eaten by the wolf) under three experimental conditions: (i) full
      attention at encoding and at retrieval; (ii) divided attention at encoding (i.e.
      performing an attention demanding secondary task) and full attention at
      retrieval; (iii) full attention at encoding and divided attention at retrieval.
      We found that confabulations in Alzheimer's disease patients were more frequent
      for the modified well-known fairy tales and when encoding was weakened by a
      concurrent secondary task (61%), compared with the other types of stories and
      experimental conditions. Confabulations in the modified fairy tales always
      consisted of elements of the original version of the fairy tale (e.g. Little Red
      Riding Hood is eaten by the wolf). This is the first experimental evidence
      showing that poor encoding and over-learned information are involved in
      confabulation in Alzheimer's disease.

PMID- 18829698
TI  - Development of methodology for conducting clinical trials in frontotemporal lobar
      degeneration.
AB  - To design clinical trials for the frontotemporal lobar degenerations (FTLD),
      knowledge about measurement of disease progression is needed to estimate power
      and enable the choice of optimal outcome measures. The aim here was to conduct a
      multicentre, 1 year replica of a clinical trial in patients with one of four FTLD
      syndromes, behavioural variant frontotemporal dementia (bvFTD), progressive
      nonfluent aphasia (PNFA), progressive logopenic aphasia (PLA) and semantic
      dementia (SMD). Patients with one of the four FTLD syndromes were recruited from
      five academic medical centres over a 2 year period. Standard operationalized
      diagnostic criteria were used. In addition to clinical inclusion and exclusion
      criteria, patients were required to exhibit focal frontal, temporal or insular
      brain atrophy or dysfunction by neuroimaging. Patients underwent
      neuropsychological, functional, behavioural, neurological and MR imaging
      assessment at baseline and approximately 12 months later. Potential outcome
      measures were examined for their rates of floor and ceiling values at baseline
      and end of study, their mean changes and variances. The neuropsychological tests
      were combined into two cognitive composites -- one for language functions and the
      other for executive functions. There were 107 patients who underwent baseline
      assessment and 78 who completed a follow-up assessment within 10-16 months. Two
      global measures, the FTLD-modified Clinical Dementia Rating (FTLD-modified CDR)
      and the Clinical Global Impression of Change (CGIC) demonstrated decline in the
      majority of patients. Several cognitive measures showed negligible floor or
      ceiling scores either at baseline or follow-up. Scores declined at follow-up in
      the majority of patients. The cognitive, executive and combined composites were
      shown to be sensitive to change across all FTLD syndromes. Patients improved at
      follow-up on the behavioural scales -- the Frontal Behavioural Inventory (22%)
      and the Neuropsychiatric Inventory (28%) -- suggesting that these instruments may
      not be ideal for clinical trial use. It was feasible to recruit FTLD patients in
      a simulated multi-centre trial. There are several candidate outcome measures --
      including the FTLD-CDR and the cognitive composites -- that could be used in
      clinical trials across the spectrum of FTLD.

PMID- 18829699
TI  - Intracellular calcium modulation of voltage-gated sodium channels in ventricular
      myocytes.
AB  - AIMS: Cardiac voltage-gated sodium channels control action potential (AP)
      upstroke and cell excitability. Intracellular calcium (Ca(i)(2+)) regulates AP
      properties by modulating various ion channels. Whether Ca(i)(2+) modulates sodium
      channels in ventricular myocytes is unresolved. We studied whether Ca(i)(2+)
      modulates sodium channels in ventricular myocytes at Ca(i)(2+) concentrations
      ([Ca(i)(2+)]) present during the cardiac AP (0-500 nM), and how this modulation
      affects sodium channel properties in heart failure (HF), a condition in which
      Ca(i)(2+) homeostasis is disturbed. METHODS AND RESULTS: Sodium current (I(Na))
      and maximal AP upstroke velocity (dV/dt(max)), a measure of I(Na), were studied
      at 20 and 37 degrees C, respectively, in freshly isolated left ventricular
      myocytes of control and HF rabbits, using whole-cell patch-clamp methodology.
      [Ca(i)(2+)] was varied using different pipette solutions, the Ca(i)(2+) buffer
      BAPTA, and caffeine administration. Elevated [Ca(i)(2+)] reduced I(Na) density
      and dV/dt(max), but caused no I(Na) gating changes. Reductions in I(Na) density
      occurred simultaneously with increase in [Ca(i)(2+)], suggesting that these
      effects were due to permeation block. Accordingly, unitary sodium current
      amplitudes were reduced at higher [Ca(i)(2+)]. While I(Na) density and gating at
      fixed [Ca(i)(2+)] were not different between HF and control, reductions in
      dV/dt(max) upon increases in stimulation rate were larger in HF than in control;
      these differences were abolished by BAPTA. CONCLUSION: Ca(i)(2+) exerts acute
      modulation of I(Na) density in ventricular myocytes, but does not modify I(Na)
      gating. These effects, occurring rapidly and in the [Ca(i)(2+)] range observed
      physiologically, may contribute to beat-to-beat regulation of cardiac
      excitability in health and disease.

PMID- 18829700
TI  - Pulse pressure to vascular cells: novel methods for solving pathogenesis in cell
      migration.

PMID- 18829701
TI  - Delayed recovery of intracellular acidosis during reperfusion prevents calpain
      activation and determines protection in postconditioned myocardium.
AB  - AIMS: Indirect data suggest that delayed recovery of intracellular pH (pHi)
      during reperfusion is involved in postconditioning protection, and calpain
      activity has been shown to be pH-dependent. We sought to characterize the effect
      of ischaemic postconditioning on pHi recovery during reperfusion and on calpain
      dependent proteolysis, an important mechanism of myocardial reperfusion injury.
      METHODS AND RESULTS: Isolated Sprague-Dawley rat hearts were submitted to 40 min
      of ischaemia and different reperfusion protocols of postconditioning and
      acidosis. pHi was monitored by (31)P-NMR spectroscopy. Myocardial cell death was
      determined by lactate dehydrogenase (LDH) and triphenyltetrazolium staining, and
      calpain activity by western blot measurement of alpha-fodrin degradation. In
      control hearts, pHi recovered within 1.5 +/- 0.24 min of reperfusion.
      Postconditioning with 6 cycles of 10 s ischaemia-reperfusion delayed pHi recovery
      slightly to 2.5 +/- 0.2 min and failed to prevent calpain-mediated alpha-fodrin
      degradation or to elicit protection. Lowering perfusion flow to 50% during
      reperfusion cycles or shortening the cycles (12 cycles of 5 s ischemia
      reperfusion) resulted in a further delay in pHi recovery (4.1 +/- 0.2 and 3.5 +/-
      0.3 min, respectively), attenuated alpha-fodrin proteolysis, improved functional
      recovery, and reduced LDH release (47 and 38%, respectively, P < 0.001) and
      infarct size (36 and 32%, respectively, P < 0.001). This cardioprotection was
      identical to that produced by lowering the pH of the perfusion buffer to 6.4
      during the first 2 min of reperfusion or by calpain inhibition with MDL-28170.
      CONCLUSION: These results provide direct evidence that postconditioning
      protection depends on prolongation of intracellular acidosis during reperfusion
      and indicate that inhibited calpain activity could contribute to this protection.

PMID- 18829702
TI  - Aneurysm of the right ventricular outflow tract after surgical repair of
      Tetralogy of Fallot: three-dimensional computed tomography findings.

PMID- 18829703
TI  - The significance of preoperative atrial fibrillation in patients undergoing
      cardiac surgery: preoperative atrial fibrillation--still underestimated opponent.
AB  - Atrial fibrillation (AF) has been described as an 'epidemic' due to its
      increasing prevalence in the ageing population. The prevalence of AF in the UK
      has risen from 0.78% in 1994 to 1.42% in 2006. The pathogenesis of AF seems to be
      multifactorial, and includes electrical and structural remodelling, and
      inflammation. As a result of recent developments in invasive cardiology together
      with improved pharmacological treatments, cardiac surgeons are increasingly
      operating on elderly patients with very advanced heart disease and other co
      existent diseases. Therefore, AF is often present before cardiac surgery,
      increasing the risk of surgery and the occurrence of postoperative complications.
      According to available data, preoperative AF (pre-AF) should be considered as a
      high-risk marker of postoperative complications, which also significantly reduces
      long-term patient survival. However, although some multivariate models have
      concluded that pre-AF seems to be an independent predictor of outcome, this does
      not prove a cause-effect relationship. Therefore, such a link would need to be
      proven in prospective randomized studies, yet to be undertaken.

PMID- 18829704
TI  - Aquaporin isoforms involved in physiological volume regulation of murine
      spermatozoa.
AB  - Murine epididymal spermatozoa were dispersed in a medium of native osmolality and
      then transferred to a hypo-osmotic medium to mimic the physiological osmotic
      challenge, as encountered upon ejaculation into the female tract. The addition of
      quinine to block sperm K(+)-channels for volume regulation resulted in a size
      increase of viable cells. Preincubation in 0.1 mM HgCl(2), a standard aquaporin
      inhibitor, prevented such cell swelling. Addition of the K(+)-ionophore
      valinomycin to quinine-swollen sperm reversed the swelling, but not after
      pretreatment of the swollen sperm by HgCl(2). Aqp7, Aqp8, and Aqp9 mRNAs were
      identified in spermatozoa by RT-PCR, and the entire open reading frames were
      sequenced and compared with the GenBank database. Western blotting demonstrated
      specific protein signals for sperm AQP7 and AQP8 expression but probably not
      AQP9. The role of Hg(2+)-insensitive AQP7, if any, in sperm volume regulation was
      studied in transgenic mice. Spermatozoa from Aqp7(-/-) mice were the same size as
      wild-type sperm in basal conditions. Quinine-swollen volume, swelling reversal by
      valinomycin, and inhibition by Hg(2+) were also similar, indicating efficient
      water transport in the absence of AQP7. However, both water influx and efflux
      occurred faster in Aqp7(-/-) sperm than wild-type. This faster water movement in
      the knockout mouse spermatozoa was explainable by an upregulation of Aqp8
      expression as revealed by quantitative PCR. Therefore, the Hg(2+)-sensitive AQP8,
      which was localized in elongated spermatids and spermatozoa, is a likely
      candidate for a water channel responsible for physiological sperm volume
      regulation crucial to in vivo fertilization.

PMID- 18829705
TI  - Segmental expression of the bradykinin type 2 receptor in rat efferent ducts and
      epididymis and its role in the regulation of aquaporin 9.
AB  - Water and solute transport in the efferent ducts and epididymis are important for
      the establishment of the appropriate luminal environment for sperm maturation and
      storage. Aquaporin 9 (AQP9) is the main water channel in the epididymis, but its
      regulation is still poorly understood. Components of the kinin-kallikrein system
      (KKS), leading to the production of bradykinin (BK), are highly expressed in the
      lumen of the male reproductive tract. We report here that the epididymal luminal
      fluid contains a significant amount of BK (2 nM). RT-PCR performed on epididymal
      epithelial cells isolated by laser capture microdissection (LCM) showed abundant
      BK type 2 receptor (Bdkrb2) mRNA expression but no type 1 receptor (Bdkrb1).
      Double-immunofluorescence staining for BDKRB2 and the anion exchanger AE2 (a
      marker of efferent duct ciliated cells) or the V-ATPase E subunit, official
      symbol ATP6V1E1 (a marker of epididymal clear cells), showed that BDKRB2 is
      expressed in the apical pole of nonciliated cells (efferent ducts) and principal
      cells (epididymis). Triple labeling for BDKRB2, AQP9, and ATP6V1E1 showed that
      BDKRB2 and AQP9 colocalize in the apical stereocilia of principal cells in the
      cauda epididymidis. While uniform Bdkrb2 mRNA expression was detected in the
      efferent ducts and along the epididymal tubule, marked variations were detected
      at the protein level. BDKRB2 was highest in the efferent ducts and cauda
      epididymidis, intermediate in the distal initial segment, moderate in the corpus,
      and undetectable in the proximal initial segment and the caput. Functional assays
      on tubules isolated from the distal initial segments showed that BK significantly
      increased AQP9-dependent glycerol apical membrane permeability. This effect was
      inhibited by BAPTA-AM, demonstrating the participation of calcium in this
      process. This study, therefore, identifies BK as an important regulator of AQP9.

PMID- 18829706
TI  - Steroidogenic capacity of residual ovarian tissue in 4-vinylcyclohexene diepoxide
      treated mice.
AB  - Menopause is an important public health issue because of its association with a
      number of disorders. Androgens produced by residual ovarian tissue after
      menopause could impact the development of these disorders. It has been unclear,
      however, whether the postmenopausal ovary retains steroidogenic capacity. Thus,
      an ovary-intact mouse model for menopause that uses the occupational chemical 4
      vinylcyclohexene diepoxide (VCD) was used to characterize the expression of
      steroidogenic genes in residual ovarian tissue of follicle-depleted mice. Female
      B6C3F1 mice (age, 28 days) were dosed daily for 20 days with either vehicle or
      VCD (160 mg kg(-1) day(-1)) to induce ovarian failure. Ovaries were collected on
      Day 181 and analyzed for mRNA and protein. Acyclic aged mice were used as
      controls for natural ovarian senescence. Relative to cycling controls, expression
      of mRNA encoding steroidogenic acute regulatory protein (Star); cholesterol side
      chain cleavage (Cyp11a1); 3beta-hydroxysteroid dehydrogenase (Hsd3b); 17alpha
      hydroxylase (Cyp17a1); scavenger receptor class B, type 1 (Scarb1); low-density
      lipoprotein receptor (Ldlr); and luteinizing hormone receptor (Lhcgr) was
      enriched in VCD-treated ovaries. In acyclic aged ovaries, mRNA expression for
      only Cyp17a1 and Lhcgr was greater than that in controls. Compared to cycling
      controls, ovaries from VCD-treated and aged mice had similar levels of HSD3B,
      CYP17A1, and LHCGR protein. The pattern of protein immunofluorescence staining
      for HSD3B in follicle-depleted (VCD-treated) ovaries was homogeneous, whereas
      that for CYP17A1 was only seen in residual interstitial cells. Circulating levels
      of FSH and LH were increased, and androstenedione levels were detectable
      following follicle depletion in VCD-treated mice. These findings support the idea
      that residual ovarian tissue in VCD-treated mice retains androgenic capacity.

PMID- 18829707
TI  - Physical protein-protein interactions predicted from microarrays.
AB  - MOTIVATION: Microarray expression data reveal functionally associated proteins.
      However, most proteins that are associated are not actually in direct physical
      contact. Predicting physical interactions directly from microarrays is both a
      challenging and important task that we addressed by developing a novel machine
      learning method optimized for this task. RESULTS: We validated our support vector
      machine-based method on several independent datasets. At the same levels of
      accuracy, our method recovered more experimentally observed physical interactions
      than a conventional correlation-based approach. Pairs predicted by our method to
      very likely interact were close in the overall network of interaction, suggesting
      our method as an aid for functional annotation. We applied the method to predict
      interactions in yeast (Saccharomyces cerevisiae). A Gene Ontology function
      annotation analysis and literature search revealed several probable and novel
      predictions worthy of future experimental validation. We therefore hope our new
      method will improve the annotation of interactions as one component of multi
      source integrated systems. SUPPLEMENTARY INFORMATION: Supplementary data are
      available at Bioinformatics online.

PMID- 18829708
TI  - Subcutaneous calcification following injection of triamcinolone hexacetonide for
      plantar fasciitis.

PMID- 18829709
TI  - Proteomic analysis of scleroderma lesional skin reveals activated wound healing
      phenotype of epidermal cell layer.
AB  - OBJECTIVE: To identify using proteomic analysis, proteins of altered abundance in
      the skin of patients with SSc. METHODS: 4 mm excision biopsies were obtained from
      the forearm involved skin of 12 diffuse SSc patients and 12 healthy controls. Two
      dimensional gel electrophoresis was used to separate and define proteins in
      normal and SSc skin biopsy material. Proteins of altered abundance in the disease
      were formally identified by mass spectroscopy. Abnormalities of the epidermis
      were confirmed by immunohistochemistry. RESULTS: Proteomic analysis revealed
      altered abundance of proteins involved in extracellular matrix production,
      myofibroblast contractility, energy metabolism and response to oxidative stress.
      In addition, proteins specific to the epidermis and involved in epidermal cell
      differentiation were altered in abundance in the disease. SSc epidermis is
      thickened, has an expanded nucleated cell layer, and exhibits abnormal
      persistence of basal marker keratin 14, delayed expression of maturation markers
      keratin 1/10 and the induction of keratins 6 and 16, normally absent from
      interfollicular skin and induced following epidermal injury. These changes
      closely resemble the activated phenotype seen during wound healing. CONCLUSIONS:
      Consistent with previous models of SSc pathogenesis these data are showing
      increased contractility, increased extracellular matrix and response to oxidative
      stress in the involved skin of recent onset SSc patients. In addition, we show
      that SSc epidermis has an activated, wound healing phenotype. These findings are
      important because epidermal cells activated by injury induce and regulate local
      fibroblasts during wound repair.

PMID- 18829710
TI  - Use of fresh frozen plasma to enhance the therapeutic action of rituximab.

PMID- 18829711
TI  - Acute spontaneous tumor lysis syndrome in a patient with squamous cell carcinoma
      of the lung.

PMID- 18829712
TI  - Improvements in glycaemic control and cardiovascular risk factors in a cohort of
      patients with type 1 diabetes over a 5-year period.
AB  - BACKGROUND: Management of patients with type 1 diabetes in the UK has changed
      over the past 20 years. The targets for glycaemic control, blood pressure and
      cholesterol are lower. We examined a cohort of patients with type 1 diabetes who
      have been through these changes to assess their effects. DESIGN AND METHODS: A
      cohort of patients with type 1 diabetes who attended a secondary care outpatient
      diabetes clinic between 1991 and 1996 were reviewed in 2001 and 2006. Comparison
      is made between current biophysical markers and those obtained in 2001. RESULTS:
      Only 81.9% (n = 214) of the original cohort attended in 2006. These patients had
      an average duration of diabetes of 23.46 (SD +/- 8.06) years. There were 134 male
      patients (62.62%). In these patients HbA1c had reduced by 0.4% (absolute
      reduction); a relative reduction of 4.41% (P = 0.0001). Statistically significant
      reductions in diastolic blood pressure (74-68 mmHg) and total cholesterol (5.37
      4.62 mmol/l) occurred. However, weight (75.04-82.31 kg) and BMI (25.32-27.72
      kg/m(2)) significantly increased. There was no statistically significant change
      in insulin dose (units/kg), serum creatinine, urinary ACR or systolic blood
      pressure. CONCLUSION: An urban setting, mobile population and patient non
      attendance can complicate modern diabetes care. Despite these difficulties, input
      by the diabetes team working with the patients can achieve small improvements in
      Hba1c and cardiovascular risk factors by increased use of long acting insulins,
      metformin, statins and blood pressure medication.

PMID- 18829713
TI  - Antenatal Bartter's syndrome: why is this not a lethal condition?
AB  - There are four themes in this teaching exercise for Professor McCance. The first
      challenge was to explain how a premature infant with Bartter's syndrome could
      survive despite having such a severe degree of renal salt wasting. Second, the
      medical team wanted to know why there was such a dramatic decrease in the
      natriuresis in response to therapy, despite the presence of a permanent molecular
      defect that affected the loop of Henle. Third, Professor McCance was asked why
      this patient seemed to have a second rare disease, AQP2 deficiency type of
      nephrogenic diabetes insipidus. The fourth challenge was to develop a diagnostic
      test to help the parents of this baby titrate the dose of indomethacin to ensure
      an effective dose while minimizing the likelihood of developing nephrotoxicity.
      The missing links in this interesting story emerge during a discussion between
      the medical team and its mentor.

PMID- 18829714
TI  - In vivo evaluation of PhiC31 recombinase activity using a self-excision cassette.
AB  - Gene targeting allows precise tailoring of the mouse genome such that desired
      modifications can be introduced under precise temporal and spatial control. This
      can be achieved through the use of site-specific recombinases, which mediate
      deletion or inversion of genomic DNA flanked by recombinase-specific recognition
      sites, coupled with gene targeting to introduce the recombinase recognition sites
      at the desired genomic locations within the mouse genome. The introduction of
      multiple modifications at the same locus often requires use of multiple
      recombination systems. The most commonly used recombination system is Cre/lox. We
      here evaluated in vivo the ability of PhiC31 phage integrase to induce a genomic
      deletion in mouse. We engineered a self-excision cassette, modeled after one
      previously designed for Cre, containing a positive selection marker and PhiC31
      driven by a testis-specific promoter, all flanked by PhiC31 specific attP/B
      sites. We found in vivo PhiC31 mediated self-excision in 38% of transmitted
      alleles, although 18% of these showed evidence of imprecise deletion.
      Furthermore, in the 69% of un-recombined cassettes, sequence analysis revealed
      that PhiC31 mediated an intra-molecular deletion of the attB site preventing any
      subsequent recombination. This study demonstrates that PhiC31 can be used to
      automatically remove Neo, in the male chimera germline, although it is not as
      efficient or as accurate as Cre.

PMID- 18829715
TI  - A novel DNA sequence periodicity decodes nucleosome positioning.
AB  - There have been two types of well-characterized DNA sequence periodicities; both
      are found to be associated with important molecular mechanisms. One is a 3-nt
      periodicity corresponding to codon triplets, the other is a 10.5-nt periodicity
      related to the structure of DNA helixes. In the process of analyzing the genome
      and transcriptome of Trichomonas vaginalis, we observed a 120.9-nt periodicity
      along DNA sequences. Different from the 3- and 10.5-nt periodicities, this novel
      periodicity originates near the 5'-end of transcripts, extends along the
      direction of transcription, and weakens gradually along transcripts. As a result,
      codon usage as well as amino acid composition is constrained by this periodicity.
      Similar periodicities were also identified in other organisms, but with variable
      length associated with the length of nucleosome units. We validated this
      association experimentally in T. vaginalis, and demonstrated that the periodicity
      manifests nucleotide variations between linker-DNA and wrapping-DNA along
      nucleosome array. We conclude that this novel DNA sequence periodicity is a
      signature of nucleosome organization suggesting that nucleosomes are well
      positioned with regularity, especially near the 5'-end of transcripts.

PMID- 18829716
TI  - Central base pair flipping and discrimination by PspGI.
AB  - PspGI is a representative of a group of restriction endonucleases that recognize
      a pentameric sequence related to CCNGG. Unlike the previously investigated
      Ecl18kI, which does not have any specificity for the central base pair, PspGI
      prefers A/T over G/C in its target site. Here, we present a structure of PspGI
      with target DNA at 1.7 A resolution. In this structure, the bases at the center
      of the recognition sequence are extruded from the DNA and flipped into pockets of
      PspGI. The flipped thymine is in the usual anti conformation, but the flipped
      adenine takes the normally unfavorable syn conformation. The results of this and
      the accompanying manuscript attribute the preference for A/T pairs over G/C pairs
      in the flipping position to the intrinsically lower penalty for flipping A/T
      pairs and to selection of the PspGI pockets against guanine and cytosine. Our
      data show that flipping can contribute to the discrimination between normal
      bases. This adds a new role to base flipping in addition to its well-known
      function in base modification and DNA damage repair.

PMID- 18829717
TI  - NRED: a database of long noncoding RNA expression.
AB  - In mammals, thousands of long non-protein-coding RNAs (ncRNAs) (>200 nt) have
      recently been described. However, the biological significance and function of the
      vast majority of these transcripts remain unclear. We have constructed a public
      repository, the Noncoding RNA Expression Database (NRED), which provides gene
      expression information for thousands of long ncRNAs in human and mouse. The
      database contains both microarray and in situ hybridization data, much of which
      is described here for the first time. NRED also supplies a rich tapestry of
      ancillary information for featured ncRNAs, including evolutionary conservation,
      secondary structure evidence, genomic context links and antisense relationships.
      The database is available at http://jsm-research.imb.uq.edu.au/NRED, and the web
      interface enables both advanced searches and data downloads. Taken together, NRED
      should significantly advance the study and understanding of long ncRNAs, and
      provides a timely and valuable resource to the scientific community.

PMID- 18829718
TI  - Archaeal RNA ligase is a homodimeric protein that catalyzes intramolecular
      ligation of single-stranded RNA and DNA.
AB  - RNA ligases participate in repair, splicing and editing pathways that either
      reseal broken RNAs or alter their primary structure. Here, we report the
      characterization of an RNA ligase from the thermophilic archaeon,
      Methanobacterium thermoautotrophicum. The 381-amino acid Methanobacterium RNA
      ligase (MthRnl) catalyzes intramolecular ligation of 5'-PO(4) single-strand RNA
      to form a covalently closed circular RNA molecule through ligase-adenylylate and
      RNA-adenylylate (AppRNA) intermediates. At the optimal temperature of 65 degrees
      C, AppRNA was predominantly ligated to a circular product. In contrast, at 35
      degrees C, phosphodiester bond formation was suppressed and the majority of the
      AppRNA was deadenylylated. Sedimentation analysis indicates that MthRnl is a
      homodimer in solution. The C-terminal 127-amino acid segment is required for
      dimerization, is itself capable of oligomeization and acts in trans to inhibit
      the ligation activity of native MthRnl. MthRnl can also join single-stranded DNA
      to form a circular molecule. The lack of specificity for RNA and DNA by MthRnl
      may exemplify an undifferentiated ancestral stage in the evolution of ATP
      dependent ligases.

PMID- 18829719
TI  - Predicting transcription factor specificity with all-atom models.
AB  - The binding of a transcription factor (TF) to a DNA operator site can initiate or
      repress the expression of a gene. Computational prediction of sites recognized by
      a TF has traditionally relied upon knowledge of several cognate sites, rather
      than an ab initio approach. Here, we examine the possibility of using structure
      based energy calculations that require no knowledge of bound sites but rather
      start with the structure of a protein-DNA complex. We study the PurR Escherichia
      coli TF, and explore to which extent atomistic models of protein-DNA complexes
      can be used to distinguish between cognate and noncognate DNA sites. Particular
      emphasis is placed on systematic evaluation of this approach by comparing its
      performance with bioinformatic methods, by testing it against random decoys and
      sites of homologous TFs. We also examine a set of experimental mutations in both
      DNA and the protein. Using our explicit estimates of energy, we show that the
      specificity for PurR is dominated by direct protein-DNA interactions, and weakly
      influenced by bending of DNA.

PMID- 18829721
TI  - Daptomycin: rationale and role in the management of skin and soft tissue
      infections.
AB  - The emergence of community-associated methicillin-resistant Staphylococcus aureus
      (MRSA) and glycopeptide tolerance in S. aureus has underlined the importance of
      the newer anti-MRSA agents, particularly in the management of complicated skin
      and soft tissue infections (cSSTIs). The novel cyclic lipopeptide antibiotic
      daptomycin shows marked in vitro cidality against MRSA compared with both
      vancomycin and linezolid. Although comparative studies in cSSTIs have
      demonstrated non-inferiority with vancomycin and semi-synthetic penicillins, data
      from both clinical trials and observational studies suggest in vivo cidality as
      evidenced by rapid resolution of clinical signs of local inflammation and reduced
      duration of therapy. Overall success in SSTI post-marketing studies is >90%, and
      >88% in MRSA-infected patients, with no difference in the outcome observed
      between those with complicated versus uncomplicated infections. When used at
      licensed doses (4-6 mg/kg), daptomycin is safe and effective in SSTIs with
      significant muscle toxicity occurring in only 0.4% to 2.5% of patients. Clinical
      failure in daptomycin-treated SSTIs is associated with severity of infection
      (creatinine clearance <30 mL/min, intensive care unit stay and sepsis syndrome).
      Higher dosing at 6 mg/kg (with increased dosing interval in renal failure) should
      be considered in such patients as well as those at risk of bacteraemia,
      osteomyelitis, diabetic foot infection and in situations where there is more
      rapid drug clearance, such as infections complicating intravenous drug use and
      thermal burns. Once-daily dosing allows ease of use in both hospital and
      outpatient settings and may facilitate early discharge or avoided admission in
      some patient groups with SSTIs. Clinical experience to date suggests potential
      economic advantages associated with earlier hospital discharge and shorter
      duration of therapy, although further detailed cost-effectiveness comparisons are
      required to validate these observations in different healthcare settings.

PMID- 18829720
TI  - Testing the palindromic target site model for DNA transposon insertion using the
      Drosophila melanogaster P-element.
AB  - Understanding the molecular mechanisms that influence transposable element target
      site preferences is a fundamental challenge in functional and evolutionary
      genomics. Large-scale transposon insertion projects provide excellent material to
      study target site preferences in the absence of confounding effects of post
      insertion evolutionary change. Growing evidence from a wide variety of
      prokaryotes and eukaryotes indicates that DNA transposons recognize staggered-cut
      palindromic target site motifs (TSMs). Here, we use over 10 000 accurately mapped
      P-element insertions in the Drosophila melanogaster genome to test predictions of
      the staggered-cut palindromic target site model for DNA transposon insertion. We
      provide evidence that the P-element targets a 14-bp palindromic motif that can be
      identified at the primary sequence level, which predicts the local spacing,
      hotspots and strand orientation of P-element insertions. Intriguingly, we find
      that the although P-element destroys the complete 14-bp target site upon
      insertion, the terminal three nucleotides of the P-element inverted repeats
      complement and restore the original TSM, suggesting a mechanistic link between
      transposon target sites and their terminal inverted repeats. Finally, we discuss
      how the staggered-cut palindromic target site model can be used to assess the
      accuracy of genome mappings for annotated P-element insertions.

PMID- 18829722
TI  - Daptomycin in endocarditis and bacteraemia: a British perspective.
AB  - Assessment of the place of daptomycin in the treatment of endocarditis and
      bacteraemia requires assimilation of data from one open-label randomized
      comparative clinical trial sized for equivalence, from registry data and from
      case reports. Selected relevant animal models and in vitro data are also
      considered in an effort to produce an integrated assessment of the current place
      of daptomycin in treatment. The evidence for the use of daptomycin is best in
      Staphylococcus aureus bacteraemia and endocarditis, but also includes some data
      on infections due to Enterococcus spp., especially if vancomycin-resistant. The
      emergence of resistance in a minority of patients on current dose regimens may
      mean that trials have to be repeated with higher doses, or the drug used in a
      combined therapy where rifampicin may be the best choice. In general, equivalence
      to comparator antibiotic regimens and a correlation for in vitro and in vivo
      findings have been demonstrated, but there are important gaps in the clinical
      data including a comparative equivalence trial in streptococcal and enterococcal
      endocarditis. Clinical benefit might be anticipated, but has not been proved,
      over aminoglycoside-containing regimens, and economic assessments are critical in
      the decision as to when and how daptomycin is deployed.

PMID- 18829723
TI  - Who's winning the war?
AB  - Traditionally, methicillin-resistant Staphylococcus aureus (MRSA) has been seen
      as an infection control problem in healthcare communities. It is now clear that
      antibiotic use is also an important factor in the control of MRSA, both in the
      treatment of infection and also, paradoxically perhaps, as a cause of the MRSA
      problem, in the same way that antibiotic use causes Clostridium difficile
      disease. At both levels, major improvements in the quality of our antibiotic use
      are required, particularly antibiotic stewardship to reduce the selection,
      maintenance and transmission of MRSA strains. In addition, new agents are
      required to reduce our reliance on glycopeptides for the treatment of serious
      MRSA infections. Daptomycin has great promise in this regard as its rapid
      bactericidal activity makes it particularly suitable for the treatment of
      bacteraemia and endocarditis.

PMID- 18829724
TI  - Clinical experience with daptomycin: bacteraemia and endocarditis.
AB  - Serious infections due to Staphylococcus aureus, especially those due to
      methicillin-resistant S. aureus, have become a major challenge. Vancomycin has
      long been the drug of choice for treatment of such infections, but failures due
      to its slow bactericidal activity coupled with increasing MICs have necessitated
      a search for new, more effective agents. Daptomycin has been studied by a number
      of investigators and has proved to be effective for bacteraemic infections due to
      staphylococci as well as vancomycin-resistant enterococci and other Gram-positive
      organisms. In addition, in a randomized controlled trial comparing daptomycin
      monotherapy with potentially synergistic therapy with either vancomycin or beta
      lactam, both used in combination with an aminoglycoside, daptomycin achieved
      comparable outcomes but with significantly less nephrotoxicity.

PMID- 18829725
TI  - Future directions with daptomycin.
AB  - Daptomycin is the first new natural-product antibiotic launched in a generation.
      It was licensed first for skin and soft tissue infections (SSTIs) and, more
      recently, for staphylococcal bacteraemia and endocarditis. Further clinical
      trials are in progress, some investigating performance in subsets of SSTIs while
      others, more interestingly, are evaluating efficacy in enterococcal endocarditis
      and neutropenic fevers--settings where the compound's bactericidal activity is
      potentially advantageous. There is a need for further trials in bone and joint
      infections. On the negative side, there are several reports of mutational
      resistance emerging during the treatment of methicillin-resistant Staphylococcus
      aureus (MRSA) infections, mostly in settings with a heavy bacterial load, and
      there is a need to determine whether higher dosages or combination regimens will
      reduce this risk. A few patients have already been treated with doses of up to 12
      mg/kg. Lastly, daptomycin is entering a market increasingly crowded with new anti
      Gram-positive agents. More work is required to establish those settings where
      daptomycin and other new compounds offer real advantages over established
      glycopeptides and over each other. There is presently a paradox whereby
      vancomycin is agreed to be less than ideal, with outcomes impaired against MRSA
      with modestly raised MICs, but where new agents have yet to demonstrate
      unequivocal superiority.

PMID- 18829726
TI  - Pre-clinical experience with daptomycin.
AB  - Daptomycin is a broad-spectrum, bactericidal agent active against Gram-positive
      bacteria, acting largely and unusually through membrane depolarization. Activity
      is markedly affected in vitro by the availability of calcium ions, and its high
      molecular weight with associated poor diffusion means that conventional disc
      diffusion testing is not reliable (and as a consequence not available). In order
      to allow susceptibility categorization, it is recommended that the MIC be
      determined in the presence of a defined calcium concentration. The activity of
      daptomycin is concentration-dependent with a prolonged post-antibiotic effect. It
      has linear pharmacokinetics, with a half-life of 8-9 h, the primary route of
      excretion is renal, it exhibits serum protein binding of approximately 92% and
      there is no interaction with the P450 cytochrome. Daptomycin is inactivated by
      surfactant in the lung and, in consequence, is not recommended for the treatment
      of respiratory infections. Daptomycin is currently licensed for the treatment of
      complicated skin and soft tissue infections and for bacteraemia and right-sided
      endocarditis due to methicillin-susceptible and -resistant Staphylococcus aureus.
      To date, daptomycin-resistant bacteria have rarely been isolated from patients,
      although increases in vancomycin MIC may be linked to reduced susceptibility to
      daptomycin. Close monitoring of resistance is essential to maintain the clinical
      utility of the drug. Using once-daily dosing, daptomycin has been generally well
      tolerated; however, weekly monitoring of creatinine phosphokinase is recommended,
      as myopathy in skeletal muscles has been seen, albeit rarely. The rapid
      bactericidal action of daptomycin makes it a useful addition to the therapeutic
      armamentarium for the treatment of Gram-positive infections, providing a valuable
      alternative to vancomycin when it is inappropriate or resistance is a problem.

PMID- 18829727
TI  - Sensitization by 5-azacytidine toward death receptor-induced hepatic apoptosis.
AB  - 5-Azacytidine (5-aza-CR) is a DNA-hypomethylating antineoplastic agent used
      because of its inhibitory activity on DNA methyltransferases. Today, it is
      approved as an epigenetically active drug therapy for treatment of
      myelodysplastic disorders, with a contraindication as to pre-existing liver
      diseases. Because the mechanism of its hepatotoxicity is still unknown, we
      investigated the pharmacodynamic properties of 5-aza-CR with regard to death
      receptor/ligand-induced apoptosis and the mode of execution of cell death. In a
      time- and concentration-dependent manner, primary murine, human hepatocytes and
      HepG2 cells exposed to 5-aza-CR became highly sensitive toward cell death induced
      by CD95L, tumor necrosis factor (TNF)-related apoptosis-inducing ligand, or TNF.
      Cell death was characterized as apoptotic by membrane blebbing, chromatin
      condensation, and exposure of phosphatidylserine on the outer membrane. Neither 5
      aza-2'-deoxycytidine nor the common DNA methyltransferase inhibitors S-(5'
      adenosyl)-L-homocysteine or RG 108 showed any significant effects under these
      conditions. Despite the complete protection of HepG2 by high concentrations of
      the pan-caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp(O-Me) fluoromethyl
      ketone (z-VAD-fmk), effector caspase-3/7 activity was completely abolished at
      approximately a 20-fold lower concentration of z-VAD-fmk. Under these conditions,
      the serine protease inhibitors N,alpha-tosyl-L-phenylalanine chloromethyl ketone,
      N,p-tosyl-L-lysine chloromethyl ketone, and 4-(2-aminoethyl)-benzenesulfonyl
      fluoride, respectively, conferred protection against death receptor ligands. We
      conclude that this caspase-independent apoptosis is executed by a yet
      unidentified serine protease.

PMID- 18829728
TI  - A case for deliberation in response to hormesis research.
AB  - Research on the phenomenon of hormesis (i.e., low-dose stimulatory effects caused
      by normally inhibitory or toxic substances) has recently provoked a good deal of
      debate. Formal mechanisms for deliberation and public participation are
      increasingly popular strategies for responding to controversial decisions in
      environmental policy, but they have been used only to a limited extent in
      response to scientific research itself. This commentary introduces natural
      scientists to some of the social scientific literature on these issues and argues
      for the importance of "diagnosing" whether controversial areas of policy relevant
      research would benefit from some form of deliberation. It provides a tentative
      diagnosis in the case of hormesis research, recommending a varied deliberative
      approach. There are many reasons to pursue broadly based deliberation in response
      to hormesis, including the potential to promote more productive research
      projects, alleviate public distrust, and prevent bias. Deliberative proceedings
      in this case should address judgments associated with at least four activities:
      (1) choosing projects and designing studies, (2) developing terminology, (3)
      interpreting and evaluating studies, and (4) applying research results to public
      policy. Although an advisory group composed primarily of experts might provide an
      adequate starting point, more intensive deliberative processes would be valuable
      before developing major changes to regulatory policy.

PMID- 18829729
TI  - Expert opinion: fomepizole may ameliorate the need for hemodialysis in methanol
      poisoning.
AB  - Fomepizole is now the antidote of choice in methanol poisoning. The use of
      fomepizole may also change the indications for hemodialysis in these patients. We
      have addressed this change in a review of articles on methanol poisonings. Review
      of the literature (through PubMed) combined with our own experiences from two
      recent methanol outbreaks in Estonia and Norway. The efficiency of dialysis
      during fomepizole treatment was reported in only a few reports. One recent study
      challenged the old indications, suggesting a new approach with delayed or even no
      hemodialysis. Methanol-poisoned patients on fomepizole treatment may be separated
      into two categories: 1) The critically ill patient, with severe metabolic
      acidosis (base deficit >15 mM) and/or visual disturbances should be given buffer,
      fomepizole and immediate hemodialysis: dialysis removes the toxic anion formate,
      and assists in correcting the metabolic acidosis, thereby also reducing formate
      toxicity. The removal of methanol per se is not important in this setting because
      fomepizole prevents further production of formic acid. 2) The stable patient,
      with less metabolic acidosis and no visual disturbances, should be given buffer
      and fomepizole. This treatment allows for the possibility to delay, or even drop,
      dialysis in this setting, because patients will not develop more clinical
      features from methanol poisoning when fomepizole and bicarbonate is given in
      adequate doses. Indications and triage for hemodialysis in methanol poisonings
      should be modified. Delayed hemodialysis or even no hemodialysis may be an option
      in selected cases.

PMID- 18829730
TI  - Caffeic acid phenethyl ester modulates methotrexate-induced oxidative stress in
      testes of rat.
AB  - The aim of this study was to investigate the possible protective role of caffeic
      acid phenethyl ester on testicular toxicity of methotrexate in rats. Nineteen
      male rats were divided into three groups as follows: group I, control; group II,
      methotrexate-treated; group III, methotrexate + caffeic acid phenethyl ester
      treated. In the second day of experiment, a single dose of methotrexate was
      intraperitoneally administered to groups II and III, although a daily single dose
      of caffeic acid phenethyl ester was intraperitoneally administered to group III
      for 7 days. At the end of the experiment, the testes of the animals were removed
      and weighed. In the tissue, the level of lipid peroxidation as malondialdehyde
      and activities of superoxide dismutase were higher in the methotrexate group than
      in the control group. Lipid peroxidation levels and superoxide dismutase
      activities were decreased in caffeic acid phenethyl ester + methotrexate group
      compared with methotrexate group. The activities of catalase in the methotrexate
      group decreased insignificantly although its activities were significantly
      increased by caffeic acid phenethyl ester administration. The activity of
      glutathione peroxidase did not change in the groups. There was significant
      difference in body weight between control and methotrexate-induced groups. In
      conclusion, the administration of methotrexate causes elevation of oxidative
      stress although treatment with caffeic acid phenethyl ester has protective
      effects on the oxidative stress in testes.

PMID- 18829731
TI  - Electrophysiological safety of sibutramine HCl.
AB  - Sibutramine is known to induce cardiovascular side effects such as tachycardia,
      vasodilation, and hypertension. The present study was aimed to examine the
      effects of sibutramine on action potential of guinea pig papillary muscle,
      recombinant hERG currents (IhERG), and inward currents (INa and ICa) of rat
      ventricular myocytes. Sibutramine at 30 mug/mL induced a shortening of action
      potential duration (APD) of guinea pig papillary muscle; on average, APD30 and
      APD90 were shortened by 23% and 17% at a stimulation rate of 1 Hz, respectively.
      Sibutramine suppressed the following currents: IhERG (IC50:2.408 +/- 0.5117
      microg/mL), L-type Ca current (IC50:2.709 +/- 0.4701 microg/mL), and Na current
      (IC50:7.718 +/- 1.7368 microg/mL). Sibutramine blocked IhERG, ICa, and INa in a
      concentration-dependent manner. In conclusion, sibutramine exerted a shortening
      effect on APD in guinea pig papillary muscle through its more powerful blocking
      effects on ICa and INa rather than IhERG.

PMID- 18829732
TI  - A nutrient mixture suppresses carbon tetrachloride-induced acute hepatic toxicity
      in ICR mice.
AB  - We examined the effect of a nutrient mixture (NM) that contains lysine, proline,
      ascorbic acid, and green tea extract in mice treated with carbon tetrachloride
      (CCl4), a model of liver injury in which free radical, oxidative stress, and
      cytokine production are closely linked. Seven-week-old male Imprinting Control
      Region (ICR) mice were divided into four groups (A-D) of five animals each.
      Groups A and C mice were fed a regular diet for 2 weeks, whereas groups B and D
      mice were supplemented with 0.5% NM (w/w) during that period. Groups A and B
      received corn oil i.p., whereas groups C and D received CCl4 (25 microL/kg, in
      corn oil, i.p.). All animals were killed 24 h after CCl4 administration, serum
      was collected to assess liver and kidney functions, and livers and kidneys were
      excised for histology. Mean serum aspartate aminotransferase and alanine
      aminotransferase were comparable in groups A and B, increased markedly in group
      C, and significantly lowered in group D compared with group C. CCl4 had no
      significant effect on renal markers (blood urea nitrogen [BUN], creatinine, and
      BUN/creatinine ratio). CCl4 administration caused an intense degree of liver
      necrosis that was less severe in the NM fed group D. These results indicate that
      NM could be a useful supplement in preventing acute chemical-induced liver
      toxicity.

PMID- 18829733
TI  - Incidence of poisoning deaths in Finland in 1971-2005.
AB  - Poisonings cause considerable morbidity and mortality worldwide. However, only
      few countries have published nationwide statistics on poisoning deaths. Based on
      the Official Cause-of-Death Statistics of Finland, we investigated the incidence
      and secular trend of poisoning deaths in Finland in 1971-2005. Alcohol poisoning
      deaths and other poisoning deaths were analyzed separately. During the 35-year
      study period, other poisoning deaths (non-alcohol) increased from 2.6/100,000 in
      men and 1.4/100,000 in women in 1971 to 6.8/100,000 and 3.2/100,000 in 2005,
      respectively. Alcohol poisoning death rates also increased from 9.6/100,000 in
      men and 0.7/100,000 in women in 1971 to 16.8/100,000 and 4.2/100,000 in 2005,
      respectively. In the early 1970s, the incidence rates of alcohol deaths were
      about 10 times higher in men compared with women, whereas in the last few years
      of observation, men's incidence rate was only about four times higher. Our study
      showed that alcohol and other poisoning deaths increased in Finland between 1971
      and 2005. Men's risk was markedly higher than women's risk, but in the later
      years, women's risk was increasing. Poisoning death rates among children and
      adolescents were low throughout the period.

PMID- 18829734
TI  - Adult metformin ingestions reported to Texas poison control centers, 2000-2006.
AB  - Metformin is an oral hypoglycemic agent used in the management of type 2 diabetes
      mellitus. Limited information exists on adult metformin ingestions reported to
      poison control centers. The distribution of adult metformin ingestions reported
      to Texas poison control centers during 2000-2006 was determined for various
      factors. In addition, triage guidelines for the management of isolated ingestions
      were drafted. Of 1528 total metformin ingestions, 58% involved coingestants. Of
      the 264 ingestions of metformin alone, where the final medical outcome was known,
      dose ingested was reported for 66%. The mean reported dose was 4739 mg (range 500
      60,000 mg). Ingestions of < or =2500 mg and >5000 mg reported doses differed with
      respect to the proportion involving suspected attempted suicide (6% versus 81%),
      serious final medical outcome (3% versus 19%), and referral to a health care
      facility (3% versus 83%). Using 5000 mg as a threshold dose for referral to a
      health care facility, 91% of cases not already at or en route to a health care
      facility were managed according drafted triage guidelines.

PMID- 18829735
TI  - Early-onset pancytopenia and skin ulcer following low-dose methotrexate therapy.
AB  - Pancytopenia is a rare but serious adverse effect of low-dose methotrexate (MTX)
      sodium therapy, and this case report describes a very early-onset of pancytopenia
      and cutaneous lesions after three days of ingestion. A 64-year-old man was
      presented to Emergency Department with weakness, fever, poor appetite, nausea,
      and vomiting after he had had accidentally ingested MTX tablets (2.5 mg) twice a
      day for the last three days. On initial examination, several painful lesions in
      his oral mucosa and a cutaneous ulceration on his right foot were also observed.
      He had severe pancytopenia, poor kidney functions, and abnormal coagulation
      parameters. The blood level of MTX was found to be within therapeutic range. He
      was treated with leucovorine, intravenous antibiotics, and appropriate blood
      transfusions; he was discharged from hospital without any sequela. Pancytopenia
      associated with low-dose (cumulative dose of 15 mg in 3 days) MTX therapy had not
      been reported previously. The Naranjo probability scale showed pancytopenia and
      skin ulcer associated with low-dose MTX therapy as probable adverse reactions.
      Risk factors for pancytopenia such as renal insufficiency, hypoalbuminemia, low
      folate levels, concomitant infections, concomitant use of drugs, and folate
      supplementation were not identified in our patient. Although pancytopenia
      associated with low-dose MTX therapy is not expected as early as 3 days after
      initiation of the therapy, physicians should also be aware of this life
      threatening adverse effect during the very first days of MTX therapy for
      rheumatoid arthritis patients.

PMID- 18829736
TI  - Hyperglycemia in acute aluminum phosphide poisoning as a potential prognostic
      factor.
AB  - Aluminum phosphide (AlP) is a solid fumigant widely used in Iran as a grain
      preservative. When reacted with water or acids, AIP produces phosphine gas, a
      mitochondrial poison that interferes with oxidative phosphorylation and protein
      synthesis. Poisoning by AIP is one of the most important causes of fatal chemical
      toxicity in Iran. There are few studies in the medical literature addressing
      prognostic factors associated with AlP poisoning. In this prospective study
      conducted across a 14-month period commencing on 21st March 2006, we enrolled all
      patients admitted to the ICU of Loghman-Hakim Hospital Poison Center (Tehran,
      Iran) with AIP poisoning, no history of diabetes mellitus diagnosed before
      hospitalization, and normal body mass index. We recorded patient-specific
      demographic information, blood glucose level on presentation (before treatment),
      arterial blood gas (ABG) analysis, time elapsed between ingestion and
      presentation, ingested dose, duration of intensive care admission, and outcome
      data related to each presentation. We enrolled the group of patients who survived
      the intoxication as a control group and compared their blood glucose levels with
      those who died because of AlP poisoning. Data were analyzed by Statistical
      Product and Service Solutions (SPSS) software (Version 12; Chicago, Ilinois, USA)
      using logistic regression, Pearson correlation coefficient and Student's t-test.
      P values of 0.05 or less were considered as the statistical significant levels.
      Forty-five patients (21 women and 24 men) with acute AlP poisoning were included
      in the study. The mean age was 27.3 +/- 11.5 years (range: 14-62 years). Thirteen
      patients survived (29%) and 32 expired (71%). AlP poisoning followed deliberate
      ingestion in all patients. The time elapsed between ingestion and arrival at the
      hospital was 3.2 +/- 0.4 h. There was no significant difference between survived
      and non-survived groups according to age, gender, and time to treatment. However,
      the difference between mean blood glucose levels in survived (143.4 +/- 13.7
      mg/dL) and non-survived (222.6 +/- 20 mg/dL) cases was statistically significant
      (P = 0.021). There was no significant correlation between blood glucose level and
      time to treatment, age, gender, pH, HCO3 concentration, and ingested dose. Twenty
      three (71.9%) of non-survived and four (30.8%) of survived patients had a blood
      glucose level greater than 140 mg/dL. After adjusting according to age, gender,
      ingested dose, pH and HCO3 concentration The odds ratio for hyperglycemia as a
      risk factor for death was 5.7 (CI of 1.4-23.4). In our study, patients who
      succumbed to AIP poisoning had significantly higher mean blood glucose levels
      than those who survived. This correlation of hyperglycemic effect and mortality
      suggests that it may be useful in guiding risk assessment and treatment of AIP
      poisoning. Management of hyperglycemia may have a useful role in treatment of
      these patients by allowing increased entrance of glucose into cells and reducing
      oxygen consumption.

PMID- 18829737
TI  - Failure to upregulate the adenosine2A receptor-epoxyeicosatrienoic acid pathway
      contributes to the development of hypertension in Dahl salt-sensitive rats.
AB  - Adenosine-activated renovascular dilatation in Sprague-Dawley (SD) rats is
      mediated by stimulating adenosine(2A) receptors (A(2A)R), which is linked to
      epoxyeicosatrienoic acid (EET) synthesis. The A(2A)R-EET pathway is upregulated
      by high salt (HS) intake in normotensive SD rats. Because this pathway is
      antipressor, we examined the role of the A(2A)R-EET pathway in Dahl salt
      sensitive (SS) rats. Male Dahl salt-resistant (SR) and SS rats were fed either HS
      (8.0% NaCl) or normal salt (NS; 0.4% NaCl) diet for 7 days. On day 8, isolated
      kidneys were perfused with Krebs-Henseleit buffer containing indomethacin and
      N(G)-nitro-l-arginine methyl ester and preconstricted with phenylephrine. Bolus
      injections of the stable adenosine analog 2-chloroadenosine (2-CA; 0.1-20 microg)
      elicited dose-dependent dilation in both Dahl SR and SS rats. Dahl SR rats fed a
      HS diet demonstrated a greater renal vasodilator response to 10 microg of 2-CA,
      as measured by the reduction in renal perfusion pressure, than that of Dahl SR
      rats fed a NS diet (-104 +/- 6 vs. -77 +/- 7 mmHg, respectively; P < 0.05). In
      contrast, Dahl SS rats did not exhibit a difference in the vasodilator response
      to 2-CA whether fed NS or HS diet (96 +/- 6 vs. 104 +/- 13 mmHg in NS- and HS-fed
      rats, respectively). In Dahl SR but not Dahl SS rats, HS intake significantly
      increased purine flux, augmented the protein expression of A(2A)R and the
      cytochrome P-450 2C23 and 2C11 epoxygenases, and elevated the renal efflux of
      EETs. Thus the Dahl SR rat is able to respond to HS intake by recruiting EET
      formation, whereas the Dahl SS rat appears to have exhausted its ability to
      increase EET synthesis above the levels observed on NS intake, and this inability
      of Dahl SS rats to upregulate the A(2A)R-EET pathway in response to salt loading
      may contribute to the development of salt-sensitive hypertension.

PMID- 18829738
TI  - Intermedin ameliorates vascular and renal injury by inhibition of oxidative
      stress.
AB  - Intermedin (IMD) is a newly discovered peptide related to calcitonin gene-related
      peptide and adrenomedullin, and has been shown to reduce blood pressure and
      reactive oxygen species formation in vivo. In this study, we determined whether
      IMD exerts vascular and renal protection in DOCA-salt hypertensive rats by
      intravenous injection of adenovirus harboring the human IMD gene. Expression of
      human IMD was detected in the rat kidney via immunohistochemistry. IMD
      administration significantly lowered blood pressure, increased urine volume, and
      restored creatinine clearance. IMD also dramatically decreased superoxide
      formation and media thickness in the aorta. Vascular injury in the kidney was
      reduced by IMD gene delivery as evidenced by the prevention of glomerular and
      peritubular capillary loss. Moreover, IMD lessened morphological damage of the
      renal tubulointerstitium and reduced glomerular injury and hypertrophy.
      Attenuation of inflammatory cell accumulation in the kidney by IMD was
      accompanied by inhibition of p38MAPK activation and intercellular adhesion
      molecule 1 expression. In addition, IMD gene transfer resulted in a marked
      decline in myofibroblast and collagen accumulation in association with decreased
      transforming growth factor-beta1 levels. Furthermore, IMD increased nitric oxide
      excretion in the urine and lowered the amount of lipid peroxidation. These
      results demonstrate that IMD is a powerful renal protective agent with
      pleiotropic effects by preventing endothelial cell loss, kidney damage,
      inflammation, and fibrosis in hypertensive DOCA-salt rats via inhibition of
      oxidative stress and proinflammatory mediator pathways.

PMID- 18829739
TI  - Analysis of DNA breaks, DNA damage response, and apoptosis produced by high NaCl.
AB  - We previously reported that, both in cell culture and in the renal inner medulla
      in vivo, elevating NaCl increased the number of DNA breaks, which persisted as
      long as NaCl remained high but were rapidly repaired when NaCl was lowered.
      Furthermore, those breaks did not induce the DNA repair protein gammaH2AX or
      cause activation of the MRN (Mre11, Rad50, Nbs1) complex. In contrast, others
      recently reported that high NaCl does induce gammaH2AX and MRN complex formation
      and concluded that these activities are associated with repair of the DNA (Sheen
      MR, Kim SW, Jung JY, Ahn JY, Rhee JG, Kwon HM, Woo SK. Am J Physiol Renal Physiol
      291: F1014-F1020, 2006). The purpose of the present studies was to resolve the
      disparity. The important difference is that HeLa cells, which were the main
      subject of the later report, are much less tolerant of high NaCl than are the
      mIMCD3 cells, which were our main subject. mIMCD3 cells survive levels of NaCl
      that kill HeLa cells by apoptosis. Here we demonstrate that in both cell types
      raising NaCl to a level that the cells survive (higher for mIMCD3 than HeLa)
      increases DNA breaks without inducing gammaH2AX or activating the MRN complex and
      that the DNA breaks persist as long as NaCl remains elevated, but are rapidly
      repaired when it is lowered. Importantly, in both cell types, raising NaCl
      further to cause apoptosis activates these DNA damage response proteins and
      greatly fragments DNA, associated with cell death. We conclude that gammaH2AX
      induction and MRN activation in response to high NaCl are associated with
      apoptosis, not DNA repair.

PMID- 18829740
TI  - Acceleration of polycystic kidney disease progression in cpk mice carrying a
      deletion in the homeodomain protein Cux1.
AB  - Polycystic kidney diseases (PKD) are inherited as autosomal dominant (ADPKD) or
      autosomal recessive (ARPKD) traits and are characterized by progressive
      enlargement of renal cysts. Aberrant cell proliferation is a key feature in the
      progression of PKD. Cux1 is a homeobox gene that is related to Drosophila cut and
      is the murine homolog of human CDP (CCAAT Displacement Protein). Cux1 represses
      the cyclin kinase inhibitors p21 and p27, and transgenic mice ectopically
      expressing Cux1 develop renal hyperplasia. However, Cux1 transgenic mice do not
      develop PKD. Here, we show that a 246 amino acid deletion in Cux1 accelerates PKD
      progression in cpk mice. Cystic kidneys isolated from 10-day-old cpk/Cux1 double
      mutant mice were significantly larger than kidneys from 10-day-old cpk mice.
      Moreover, renal function was significantly reduced in the Cux1 mutant cpk mice,
      compared with cpk mice. The mutant Cux1 protein was ectopically expressed in cyst
      lining cells, where expression corresponded to increased cell proliferation and
      apoptosis, and a decrease in expression of the cyclin kinase inhibitors p27 and
      p21. While the mutant Cux1 protein altered PKD progression, kidneys from mice
      carrying the mutant Cux1 protein alone were phenotypically normal, suggesting the
      Cux1 mutation modifies PKD progression in cpk mice. During cell cycle
      progression, Cux1 is proteolytically processed by a nuclear isoform of the
      cysteine protease cathepsin-L. Analysis of the deleted sequences reveals that a
      cathepsin-L processing site in Cux1 is deleted. Moreover, nuclear cathepsin-L is
      significantly reduced in both human ADPKD cells and in Pkd1 null kidneys,
      corresponding to increased levels of Cux1 protein in the cystic cells and
      kidneys. These results suggest a mechanism in which reduced Cux1 processing by
      cathepsin-L results in the accumulation of Cux1, downregulation of p21/p27, and
      increased cell proliferation in PKD.

PMID- 18829741
TI  - Aquaporin 2 expression increased by glucagon in normal rat inner medullary
      collecting ducts.
AB  - It is well known that Glucagon (Gl) is released after a high protein diet and
      participates in water excretion by the kidney, principally after a protein meal.
      To study this effect in in vitro perfused inner medullary collecting ducts
      (IMCD), the osmotic water permeability (Pf; mum/s) at 37 degrees C and pH 7.4 in
      normal rat IMCDs (n = 36) perfused with Ringer/HCO(3) was determined. Gl (10(-7)
      M) in absence of Vasopressin (AVP) enhanced the Pf from 4.38 +/- 1.40 to 11.16 +/
      1.44 microm/s (P < 0.01). Adding 10(-8), 10(-7), and 10(-6) M Gl, the Pf
      responded in a dose-dependent manner. The protein kinase A inhibitor H8 blocked
      the Gl effect. The specific Gl inhibitor, des-His(1)-[Glu(9)] glucagon (10(-7)
      M), blocked the Gl-stimulated Pf but not the AVP-stimulated Pf. There occurred a
      partial additional effect between Gl and AVP. The cAMP level was enhanced from
      the control 1.24 +/- 0.39 to 59.70 +/- 15.18 fm/mg prot after Gl 10(-7) M in an
      IMCD cell suspension. The immunoblotting studies indicated an increase in AQP2
      protein abundance of 27% (cont 100.0 +/- 3.9 vs. Gl 127.53; P = 0.0035) in
      membrane fractions extracted from IMCD tubule suspension, incubated with 10(-6) M
      Gl. Our data showed that 1) Gl increased water absorption in a dose-dependent
      manner; 2) the anti-Gl blocked the action of Gl but not the action of AVP; 3) Gl
      stimulated the cAMP generation; 4) Gl increased the AQP2 water channel protein
      expression, leading us to conclude that Gl controls water absorption by utilizing
      a Gl receptor, rather than a AVP receptor, increasing the AQP2 protein
      expression.

PMID- 18829742
TI  - Potential role of purinergic signaling in urinary concentration in inner medulla:
      insights from P2Y2 receptor gene knockout mice.
AB  - Osmotic reabsorption of water through aquaporin-2 (AQP2) in the inner medulla is
      largely dependent on the urea concentration gradients generated by urea
      transporter (UT) isoforms. Vasopressin (AVP) increases expression of both AQP2
      and UT-A isoforms. Activation of the P2Y2 receptor (P2Y2-R) in the medullary
      collecting duct inhibits AVP-induced water flow. To gain further insights into
      the overarching effect of purinergic signaling on urinary concentration, we
      compared the protein abundances of AQP2 and UT-A isoforms between P2Y2-R knockout
      (KO) and wild-type (WT) mice under basal conditions and following AVP
      administration. Under basal conditions (a gel diet for 10 days), KO mice
      concentrated urine to a significantly higher degree, with 1.8-, 1.66-, and 1.29
      fold higher protein abundances of AQP2, UT-A1, and UT-A2, respectively, compared
      with WT, despite comparable circulating AVP levels in both groups. Infusion of 1
      desamino-8-d-arginine vasopressin (dDAVP; desmopressin; 1 ng/h sc) for 5 days
      resulted in 2.14-, 2.6-, and 2.22-fold higher protein abundances of AQP2, AQP3,
      and UT-A1, respectively, in the inner medullas of KO mice compared with WT mice.
      In response to acute (45 min) stimulation by AVP (0.2 unit/mouse sc), UT-A1
      protein increased by 1.39- and 1.54-fold in WT and KO mice, respectively. These
      data suggest that genetic deletion of P2Y2-R results in increased abundances of
      key proteins involved in urinary concentration in the inner medulla, both under
      basal conditions and following AVP administration. Thus purinergic regulation may
      play a potential overarching role in balancing the effect of AVP on the urinary
      concentration mechanism.

PMID- 18829743
TI  - Early steps of the virus replication cycle are inhibited in prostate cancer cells
      resistant to oncolytic vesicular stomatitis virus.
AB  - Vesicular stomatitis virus (VSV) is currently being studied as a candidate
      oncolytic virus for tumor therapies due to its potent tumoricidal activity.
      Previous studies have demonstrated that VSV selectively infects tumor cells due
      to defects in their antiviral pathways. These defects make them more susceptible
      to VSV-induced killing than normal cells. However, some cancer cells display
      differential sensitivity to VSV. Specifically, LNCaP prostate cancer cells are
      sensitive to infection with VSV, while PC3 prostate cancer cells are relatively
      resistant to VSV. This suggests that tumor cells vary in the extent to which they
      develop defects in antiviral pathways and, thus, permit virus replication. The
      goal of these studies was to identify the step(s) of the viral replication cycle
      that is inhibited in PC3 cells. Results showed that although attachment of VSV
      was not significantly different among cell types, penetration was delayed by 10
      to 30 min in PC3 cells relative to LNCaP cells. Primary transcription was delayed
      by 6 to 8 h in PC3 cells relative to LNCaP cells. Similarly, both secondary
      transcription and viral protein synthesis rates were delayed by about 6 to 8 h.
      The progressively increasing delay suggests that more than one step is affected
      in PC3 cells. Analysis of cellular gene expression showed that in contrast to
      LNCaP cells, PC3 cells constitutively expressed numerous antiviral gene products,
      which may enhance their resistance to VSV. These data indicate that the use of
      VSV for oncolytic virus therapy for prostate tumors may require prescreening of
      tumors for their level of susceptibility.

PMID- 18829744
TI  - Why do we not yet have a human immunodeficiency virus vaccine?

PMID- 18829745
TI  - Determinants of RNA-dependent RNA polymerase (in)fidelity revealed by kinetic
      analysis of the polymerase encoded by a foot-and-mouth disease virus mutant with
      reduced sensitivity to ribavirin.
AB  - A mutant poliovirus (PV) encoding a change in its polymerase (3Dpol) at a site
      remote from the catalytic center (G64S) confers reduced sensitivity to ribavirin
      and forms a restricted quasispecies, because G64S 3Dpol is a high-fidelity
      enzyme. A foot-and-mouth disease virus (FMDV) mutant that encodes a change in the
      polymerase catalytic site (M296I) exhibits reduced sensitivity to ribavirin
      without restricting the viral quasispecies. In order to resolve this apparent
      paradox, we have established a minimal kinetic mechanism for nucleotide addition
      by wild-type (WT) FMDV 3Dpol that permits a direct comparison to PV 3Dpol as well
      as to FMDV 3Dpol derivatives. Rate constants for correct nucleotide addition were
      on par with those of PV 3Dpol, but apparent binding constants for correct
      nucleotides were higher than those observed for PV 3Dpol. The A-to-G transition
      frequency was calculated to be 1/20,000, which is quite similar to that
      calculated for PV 3Dpol. The analysis of FMDV M296I 3Dpol revealed a decrease in
      the calculated ribavirin incorporation frequency (1/8,000) relative to that
      (1/4,000) observed for the WT enzyme. Unexpectedly, the A-to-G transition
      frequency was higher (1/8,000) than that observed for the WT enzyme. Therefore,
      FMDV selected a polymerase that increases the frequency of the misincorporation
      of natural nucleotides while specifically decreasing the frequency of the
      incorporation of ribavirin nucleotide. These studies provide a mechanistic
      framework for understanding FMDV 3Dpol structure-function relationships, provide
      the first direct analysis of the fidelity of FMDV 3Dpol in vitro, identify the
      beta9-alpha11 loop as a (in)fidelity determinant, and demonstrate that not all
      ribavirin-resistant mutants will encode high-fidelity polymerases.

PMID- 18829746
TI  - Overexpression of thiol/disulfide isomerases enhances membrane fusion directed by
      the Newcastle disease virus fusion protein.
AB  - Newcastle disease virus (NDV) fusion (F) protein directs membrane fusion, which
      is required for virus entry and cell-cell fusion. We have previously shown that
      free thiols are present in cell surface-expressed NDV F protein and that blocking
      the production of free thiols by thiol-disulfide exchange inhibitors inhibited
      the membrane fusion mediated by F protein (J Virol. 81:2328-2339, 2007).
      Extending these observations, we evaluated the role of the overexpression of two
      disulfide bond isomerases, protein disulfide isomerase (PDI) and ERdj5, in cell
      cell fusion mediated by NDV glycoproteins. The overexpression of these isomerases
      resulted in significantly increased membrane fusion, as measured by syncytium
      formation and content mixing. The overexpression of these isomerases enhanced the
      production of free thiols in F protein when expressed without hemagglutination
      neuraminidase (HN) protein but decreased free thiols in F protein expressed with
      HN protein. By evaluating the binding of conformation-sensitive antibodies, we
      found that the overexpression of these isomerases favored a postfusion
      conformation of surface-expressed F protein in the presence of HN protein. These
      results suggest that isomerases belonging to the PDI family catalyze the
      production of free thiols in F protein, and free thiols in F protein facilitate
      membrane fusion mediated by F protein.

PMID- 18829747
TI  - Identification of a residue in hepatitis C virus E2 glycoprotein that determines
      scavenger receptor BI and CD81 receptor dependency and sensitivity to
      neutralizing antibodies.
AB  - Hepatitis C virus (HCV) infection is dependent on at least three coreceptors:
      CD81, scavenger receptor BI (SR-BI), and claudin-1. The mechanism of how these
      molecules coordinate HCV entry is unknown. In this study we demonstrate that a
      cell culture-adapted JFH-1 mutant, with an amino acid change in E2 at position
      451 (G451R), has a reduced dependency on SR-BI. This altered receptor dependency
      is accompanied by an increased sensitivity to neutralization by soluble CD81 and
      enhanced binding of recombinant E2 to cell surface-expressed and soluble CD81.
      Fractionation of HCV by density gradient centrifugation allows the analysis of
      particle-lipoprotein associations. The cell culture-adapted mutation alters the
      relationship between particle density and infectivity, with the peak infectivity
      occurring at higher density than the parental virus. No association was observed
      between particle density and SR-BI or CD81 coreceptor dependence. JFH-1 G451R is
      highly sensitive to neutralization by gp-specific antibodies, suggesting
      increased epitope exposure at the virion surface. Finally, an association was
      observed between JFH-1 particle density and sensitivity to neutralizing
      antibodies (NAbs), suggesting that lipoprotein association reduces the
      sensitivity of particles to NAbs. In summary, mutation of E2 at position 451
      alters the relationship between particle density and infectivity, disrupts
      coreceptor dependence, and increases virion sensitivity to receptor mimics and
      NAbs. Our data suggest that a balanced interplay between HCV particles,
      lipoprotein components, and viral receptors allows the evasion of host immune
      responses.

PMID- 18829748
TI  - Simian immunodeficiency virus (SIV)-specific CD8+ T-cell responses in vervet
      African green monkeys chronically infected with SIVagm.
AB  - African green monkeys (AGM) do not develop overt signs of disease following
      simian immunodeficiency virus (SIV) infection. While it is still unknown how
      natural hosts like AGM can cope with this lentivirus infection, a large number of
      investigations have shown that CD8(+) T-cell responses are critical for the
      containment of AIDS viruses in humans and Asian nonhuman primates. Here we have
      compared the phenotypes of T-cell subsets and magnitudes of SIV-specific CD8(+) T
      cell responses in vervet AGM chronically infected with SIVagm and rhesus monkeys
      (RM) infected with SIVmac. In comparison to RM, vervet AGM exhibited weaker signs
      of immune activation and associated proliferation of CD8(+) T cells as detected
      by granzyme B, Ki-67, and programmed death 1 staining. By gamma interferon enzyme
      linked immunospot assay and intracellular cytokine staining, SIV Gag- and Env
      specific immune responses were detectable at variable but lower levels in vervet
      AGM than in RM. These observations demonstrate that natural hosts like SIV
      infected vervet AGM develop SIV-specific T-cell responses, but the disease-free
      course of infection does not depend on the generation of robust CD8(+) T-cell
      responses.

PMID- 18829749
TI  - Proteomic analysis reveals selective impediment of neuronal remodeling upon Borna
      disease virus infection.
AB  - The neurotropic virus Borna disease virus (BDV) persists in the central nervous
      systems of a wide variety of vertebrates and causes behavioral disorders. BDV
      represents an intriguing example of a virus whose persistence in neurons leads to
      altered brain function in the absence of overt cytolysis and inflammation. The
      bases of BDV-induced behavioral impairment remain largely unknown. To better
      characterize the neuronal response to BDV infection, we compared the proteomes of
      primary cultures of cortical neurons with and without BDV infection. We used two
      dimensional liquid chromatography fractionation, followed by protein
      identification by nanoliquid chromatography-tandem mass spectrometry. This
      analysis revealed distinct changes in proteins implicated in neurotransmission,
      neurogenesis, cytoskeleton dynamics, and the regulation of gene expression and
      chromatin remodeling. We also demonstrated the selective interference of BDV with
      processes related to the adaptative response of neurons, i.e., defects in
      proteins regulating synaptic function, global rigidification of the cytoskeleton
      network, and altered expression of transcriptional and translational repressors.
      Thus, this work provides a global view of the neuronal changes induced by BDV
      infection together with new clues to understand the mechanisms underlying the
      selective interference with neuronal plasticity and remodeling that characterizes
      BDV persistence.

PMID- 18829750
TI  - The N-terminal region of an entomopoxvirus fusolin is essential for the
      enhancement of peroral infection, whereas the C-terminal region is eliminated in
      digestive juice.
AB  - The spindles of Anomala cuprea entomopoxvirus (AncuEPV), which are composed of
      glycoprotein fusolin, are known to enhance the peroral infectivity of AncuEPV
      itself and of nucleopolyhedroviruses. This has been demonstrated to involve the
      disruption of intestinal peritrophic membrane (PM), composed of chitin matrix,
      glycosaminoglycans, and proteins. To identify essential and nonessential regions
      for this enhancement activity, AncuEPV fusolin and its deletion mutants were
      expressed in Sf21 cells using a baculovirus system, and their enhancement
      abilities were analyzed. The recombinant fusolin enhanced the peroral infectivity
      of Bombyx mori nucleopolyhedrovirus up to 320-fold and facilitated the infection
      of host insect with AncuEPV. Deletion mutagenesis revealed that the N-terminal
      region (amino acids 1 to 253), a possible chitin-binding domain, is essential for
      the enhancement of infection, whereas the C-terminal region is entirely
      dispensable. The glycosylation-defective mutants N191Q, whose Asn(191) is
      replaced with Gln, and DeltaSIG, whose signal peptide is deleted, showed
      considerably reduced and abolished enhancing activities, respectively, indicating
      that the carbohydrate chain is important in the enhancing activity.
      Interestingly, the C-terminal dispensable region was digested by a serine
      protease(s) in insect digestive juice. Moreover, both the N-terminal conserved
      region and the carbohydrate chain were necessary not only for chitin binding but
      also for stability in digestive juice. A triple amino acid replacement mutant,
      IHE (Ile-His-Glu(161) to Ala-Ala-Ala), was stable in digestive juice and had
      chitin-binding ability but did not retain its enhancing activity. These results
      suggest that the enhancement of infectivity involves more than the tolerance to
      digestive juice and chitin-binding ability.

PMID- 18829751
TI  - Glycosylation of gp41 of simian immunodeficiency virus shields epitopes that can
      be targets for neutralizing antibodies.
AB  - Human immunodeficiency virus type 1 and simian immunodeficiency virus possess
      three closely spaced, highly conserved sites for N-linked carbohydrate attachment
      in the extracellular domain of the transmembrane protein gp41. We infected rhesus
      monkeys with a variant of cloned SIVmac239 lacking the second and third sites or
      with a variant strain lacking all three of SIVmac239's glycosylation sites in
      gp41. For each mutation, asparagine (N) in the canonical N-X-S/T recognition
      sequence for carbohydrate attachment was changed to the structurally similar
      glutamine such that two nucleotide changes would be required for a reversion of
      the mutated codon. By 16 weeks, experimentally infected monkeys made antibodies
      that neutralized the mutant viruses to high titers. Such antibodies were not
      observed in monkeys infected with the parental virus. Thus, new specificities
      were revealed as a result of the carbohydrate attachment mutations, and
      antibodies of these specificities had neutralizing activity. Unlike monkeys
      infected with the parental virus, monkeys infected with the mutant viruses made
      antibodies that reacted with peptides corresponding to the sequences in this
      region. Furthermore, there was strong selective pressure for the emergence of
      variant sequences in this region during the course of infection. By analyzing the
      neutralization profiles of sequence variants, we were able to define three
      mutations (Q625R, K631N, and Q634H) in the region of the glycosylation site
      mutations that conferred resistance to neutralization by plasma from the monkeys
      infected with mutant virus. Based on the reactivity of antibodies to peptides in
      this region and the colocalization of neutralization escape mutations, we
      conclude that N-linked carbohydrates in the ectodomain of the transmembrane
      protein shield underlying epitopes that would otherwise be the direct targets of
      neutralizing antibodies.

PMID- 18829752
TI  - Lymphocytic choriomeningitis virus infection yields overlapping CD4+ and CD8+ T
      cell responses.
AB  - Activation of CD4(+) T cells helps establish and sustain other immune responses.
      We have previously shown that responses against a broad set of nine CD4(+) T-cell
      epitopes were present in the setting of lymphocytic choriomeningitis virus (LCMV)
      Armstrong infection in the context of H-2(d). This is quite disparate to the H
      2(b) setting, where only two epitopes have been identified. We were interested in
      determining whether a broad set of responses was unique to H-2(d) or whether
      additional CD4(+) T-cell epitopes could be identified in the setting of the H
      2(b) background. To pursue this question, we infected C57BL/6 mice with LCMV
      Armstrong and determined the repertoire of CD4(+) T-cell responses using
      overlapping 15-mer peptides corresponding to the LCMV Armstrong sequence. We
      confirmed positive responses by intracellular cytokine staining and major
      histocompatibility complex (MHC)-peptide binding assays. A broad repertoire of
      responses was identified, consisting of six epitopes. These epitopes originate
      from the nucleoprotein (NP) and glycoprotein (GP). Out of the six newly
      identified CD4(+) epitopes, four of them also stimulate CD8(+) T cells in a
      statistically significant manner. Furthermore, we assessed these CD4(+) T-cell
      responses during the memory phase of LCMV Armstrong infection and after infection
      with a chronic strain of LCMV and determined that a subset of the responses could
      be detected under these different conditions. This is the first example of a
      broad repertoire of shared epitopes between CD4(+) and CD8(+) T cells in the
      context of viral infection. These findings demonstrate that immunodominance is a
      complex phenomenon in the context of helper responses.

PMID- 18829753
TI  - S-adenosyl homocysteine-induced hyperpolyadenylation of vesicular stomatitis
      virus mRNA requires the methyltransferase activity of L protein.
AB  - There are many unique aspects of vesicular stomatitis virus (VSV) transcription.
      In addition to its unusual mRNA capping and methyltransferase mechanisms, the
      addition of S-adenosyl homocysteine (SAH), which is the by-product and
      competitive inhibitor of S-adenosyl methionine (SAM)-mediated methyltransferase
      reactions, leads to synthesis of poly(A) tails on the 3' end of VSV mRNAs that
      are 10- or 20-fold longer than normal. The mechanism by which this occurs is not
      understood, since it has been shown that productive transcription is not
      dependent on 5' cap methylation and full-length VSV mRNAs can be synthesized in
      the absence of SAM. To investigate this unusual phenotype, we assayed the effects
      of SAH on transcription using a panel of recombinant viruses that contained
      mutations in domain VI of the VSV L protein. The L proteins we investigated
      displayed a range of 5' cap methyltransferase activities. In the present study,
      we show that the ability of the VSV L protein to catalyze methyl transfer
      correlates with its sensitivity to SAH with respect to polyadenylation, thereby
      indicating an intriguing connection between 5' and 3' end mRNA modifications. We
      also identified an L protein mutant that hyperpolyadenylates mRNA irrespective of
      the presence or absence of exogenous SAH. Further, the data presented here show
      that the wild-type L protein hyperpolyadenylates a percentage of VSV mRNAs in
      infected cells as well as in vitro.

PMID- 18829754
TI  - Role of Ebola virus VP30 in transcription reinitiation.
AB  - VP30 is a phosphoprotein essential for the initiation of Ebola virus
      transcription. In this work, we have studied the effect of mutations in VP30
      phosphorylation sites on the ebolavirus replication cycle by using a reverse
      genetics system. We demonstrate that VP30 is involved in reinitiation of gene
      transcription and that this activity is affected by mutations at the
      phosphorylation sites.

PMID- 18829755
TI  - A linear relationship between fitness and the logarithm of the critical
      bottleneck size in vesicular stomatitis virus populations.
AB  - We explored the relationship between fitness change and population size during
      transmission in vesicular stomatitis populations of very high fitness. The
      results show a linear correlation between the logarithm of the critical
      bottleneck size (population size at which there are no significant fitness
      changes after 20 passages) and the initial fitness of the population. In
      addition, limits to fitness increases during large-population passages of very
      high-fitness strains were abolished by increasing the population size during
      transmission, indicating that beneficial variation is still available in these
      populations.

PMID- 18829756
TI  - Epigenetic silencing of human immunodeficiency virus (HIV) transcription by
      formation of restrictive chromatin structures at the viral long terminal repeat
      drives the progressive entry of HIV into latency.
AB  - The molecular mechanisms utilized by human immunodeficiency virus (HIV) to enter
      latency are poorly understood. Following the infection of Jurkat T cells with
      lentiviral vectors that express Tat in cis, gene expression is progressively
      silenced. Silencing is greatly enhanced when the lentiviral vectors carry an
      attenuated Tat gene with the H13L mutation. Individual clones of lentivirus
      infected cells showed a wide range of shutdown rates, with the majority showing a
      50% silencing frequency between 30 to 80 days. The silenced clones
      characteristically contained a small fraction (0 to 15%) of activated cells that
      continued to express d2EGFP. When d2EGFP(+) and d2EGFP(-) cell populations were
      isolated from the shutdown clones, they quickly reverted to the original
      distribution of inactive and active cells, suggesting that the d2EGFP(+) cells
      arise from stochastic fluctuations in gene expression. The detailed analysis of
      transcription initiation and elongation using chromatin immunoprecipitation
      (ChIP) assays confirms that Tat levels are restricted in the latently infected
      cells but gradually rise during proviral reactivation. ChIP assays using clones
      of latently infected cells demonstrate that the latent proviruses carry high
      levels of deacetylated histones and trimethylated histones. In contrast, the
      cellular genes IkappaB alpha and GAPDH had high levels of acetylated histones and
      no trimethylated histones. The levels of trimethylated histone H3 and HP1-alpha
      associated with HIV proviruses fell rapidly after tumor necrosis factor alpha
      activation. The progressive shutdown of HIV transcription following infection
      suggests that epigenetic mechanisms targeting chromatin structures selectively
      restrict HIV transcription initiation. This decreases Tat production below the
      levels that are required to sustain HIV gene expression.

PMID- 18829757
TI  - Excretion of human immunodeficiency virus type 1 through polarized epithelium by
      immunoglobulin A.
AB  - Human immunodeficiency virus (HIV) is transmitted primarily sexually across
      mucosal surfaces. After infection, HIV propagates initially in the lamina propria
      below the polarized epithelium and causes extensive destruction of mucosal T
      cells. Immunoglobulin A (IgA) antibodies, produced in the lamina propria and then
      transcytosed across the mucosal epithelium into the lumen, can be the first line
      of immune defense against HIV. Here, we used IgA monoclonal antibodies against
      HIV envelope proteins to investigate the abilities of polarized primate and human
      epithelial cells to excrete HIV virions from the basolateral to the apical
      surface via polymeric Ig receptor (pIgR)-mediated binding and the internalization
      of HIV-IgA immune complexes. African green monkey kidney cells expressing pIgR
      demonstrated HIV excretion that was dependent on the IgA concentration and the
      exposure time. Matched IgG antibodies with the same variable regions as the IgA
      antibodies and IgA antibodies to non-HIV antigens had no HIV excretory function.
      A mixture of two IgA anti-bodies against gp120 and gp41 showed a synergistic
      increase in the level of HIV excreted. The capacity for HIV excretion correlated
      with the ability of IgA antibodies to bind HIV and of the resulting immune
      complexes to bind pIgR. Consistent with the epithelial transcytosis of HIV-IgA
      immune complexes, the colocalization of HIV proteins and HIV-specific IgA was
      detected intracellularly by confocal microscopy. Our results suggest the
      potential of IgA antibodies to excrete HIV from mucosal lamina propria, thereby
      decreasing the viral burden, access to susceptible cells, and the chronic
      activation of the immune system.

PMID- 18829759
TI  - Absence of replication of porcine endogenous retrovirus and porcine lymphotropic
      herpesvirus type 1 with prolonged pig cell microchimerism after pig-to-baboon
      xenotransplantation.
AB  - Porcine endogenous retrovirus (PERV), porcine cytomegalovirus (PCMV), and porcine
      lymphotropic herpesvirus (PLHV) are common porcine viruses that may be activated
      with immunosuppression for xenotransplantation. Studies of viral replication or
      transmission are possible due to prolonged survival of xenografts in baboon
      recipients from human decay-accelerating factor transgenic or alpha-1,3
      galactosyltransferase gene knockout miniature swine. Ten baboons underwent
      xenotransplantation with transgenic pig organs. Graft survival was 32 to 179
      days. Recipient serial samples of peripheral blood mononuclear cells (PBMC) and
      plasma were analyzed for PCMV, PERV, and PLHV-1 nucleic acids and viral
      replication using quantitative PCR assays. The PBMC contained PERV proviral DNA
      in 10 animals, PLHV-1 DNA in 6, and PCMV in 2. PERV RNA was not detected in any
      PBMC or serum samples. Plasma PLHV-1 DNA was detected in one animal. Pig cell
      microchimerism (pig major histocompatibility complex class I and pig
      mitochondrial cytochrome c oxidase subunit II sequences) was present in all
      recipients with detectable PERV or PLHV-1 (85.5%). Productive infection of PERV
      or PLHV-1 could not be demonstrated. The PLHV-1 viral load did not increase in
      serum over time, despite prolonged graft survival and pig cell microchimerism.
      There was no association of viral loads with the nature of exogenous immune
      suppression. In conclusion, PERV provirus and PLHV-1 DNA were detected in baboons
      following porcine xenotransplantation. Viral detection appeared to be due to
      persistent pig cell microchimerism. There was no evidence of productive infection
      in recipient baboons for up to 6 months of xenograft function.

PMID- 18829758
TI  - Human T-cell lymphotropic virus type 1 nucleocapsid protein-induced structural
      changes in transactivation response DNA hairpin measured by single-molecule
      fluorescence resonance energy transfer.
AB  - Time-resolved single-molecule fluorescence spectroscopy was used to study the
      human T-cell lymphotropic virus type 1 (HTLV-1) nucleocapsid protein (NC)
      chaperone activity compared to that of the human immunodeficiency virus type 1
      (HIV-1) NC protein. HTLV-1 NC contains two zinc fingers, each having a CCHC
      binding motif similar to HIV-1 NC. HIV-1 NC is required for recognition and
      packaging of the viral RNA and is also a nucleic acid chaperone protein that
      facilitates nucleic acid restructuring during reverse transcription. Because of
      similarities in structures between the two retroviruses, we have used single
      molecule fluorescence energy transfer to investigate the chaperoning activity of
      the HTLV-1 NC protein. The results indicate that the HTLV-1 NC protein induces
      structural changes by opening the transactivation response (TAR) DNA hairpin to
      an even greater extent than HIV-1 NC. However, unlike HIV-1 NC, HTLV-1 NC does
      not chaperone the strand-transfer reaction involving TAR DNA. These results
      suggest that, despite its effective destabilization capability, HTLV-1 NC is not
      as effective at overall chaperone function as is its HIV-1 counterpart.

PMID- 18829760
TI  - Structural determinant of human La protein critical for internal initiation of
      translation of hepatitis C virus RNA.
AB  - Human La protein has been implicated in facilitating internal ribosome entry site
      (IRES)-mediated translation of hepatitis C virus (HCV). Earlier, we demonstrated
      that the RNA recognition motif (RRM) encompassing residues 112 to 184 of La
      protein [La (112-184)] interacts with the HCV IRES near the initiator AUG codon.
      A synthetic peptide, LaR2C (24-mer), derived from La RRM (112-184), retains RNA
      binding ability, competes with La protein binding to the HCV IRES, and inhibits
      translation. The peptide interferes with the assembly of 48S complexes, resulting
      in the accumulation of preinitiation complexes that are incompetent for the 60S
      ribosomal subunit joining. Here, nuclear magnetic resonance spectroscopy of the
      HCV IRES-bound peptide complex revealed putative contact points, mutations that
      showed reduced RNA binding and translation inhibitory activity. The residues
      responsible for RNA recognition were found to form a turn in the RRM (112-184)
      structure. A 7-mer peptide comprising this turn showed significant translation
      inhibitory activity. The bound structure of the peptide inferred from transferred
      nuclear Overhauser effect experiments suggests that it is a beta turn. This
      conformation is significantly different from that observed in the free RRM (112
      184) NMR structure, suggesting paths toward a better-stabilized mimetic peptide.
      Interestingly, addition of hexa-arginine tag enabled the peptide to enter Huh7
      cells and showed inhibition of HCV IRES function. More importantly, the peptide
      significantly inhibited replication of the HCV monocistronic replicon.
      Elucidation of the structural determinant of the peptide provides a basis for
      developing small peptidomimetic structures as potent anti-HCV therapeutics.

PMID- 18829761
TI  - Characterization of simian immunodeficiency virus SIVSM/human immunodeficiency
      virus type 2 Vpx function in human myeloid cells.
AB  - Human immunodeficiency virus type 2 (HIV-2)/simian immunodeficiency virus SIV(SM)
      Vpx is incorporated into virion particles and is thus present during the early
      steps of infection, when it has been reported to influence the nuclear import of
      viral DNA. We recently reported that Vpx promoted the accumulation of full-length
      viral DNA following the infection of human monocyte-derived dendritic cells
      (DCs). This positive effect was exerted following the infection of DCs with
      cognate viruses and with retroviruses as divergent as HIV-1, feline
      immunodeficiency virus, and even murine leukemia virus, leading us to suggest
      that Vpx counteracted an antiviral restriction present in DCs. Here, we show that
      Vpx is required, albeit to a different extent, for the infection of all myeloid
      but not of lymphoid cells, including monocytes, macrophages, and monocytoid THP-1
      cells that had been induced to differentiate with phorbol esters. The
      intracellular localization of Vpx was highly heterogeneous and cell type
      dependent, since Vpx localized differently in HeLa cells and DCs. Despite these
      differences, no clear correlation between the functionality of Vpx and its
      intracellular localization could be drawn. As a first insight into its function,
      we determined that SIV(SM)/HIV-2 and SIV(RCM) Vpx proteins interact with the
      DCAF1 adaptor of the Cul4-based E3 ubiquitin ligase complex recently described to
      associate with HIV-1 Vpr and HIV-2 Vpx. However, the functionality of Vpx
      proteins in the infection of DCs did not strictly correlate with DCAF1 binding,
      and knockdown experiments failed to reveal a functional role for this association
      in differentiated THP-1 cells. Lastly, when transferred in the context of a
      replication-competent viral clone, Vpx was required for replication in DCs.

PMID- 18829762
TI  - Cyclophilin A-dependent restriction of human immunodeficiency virus type 1 capsid
      mutants for infection of nondividing cells.
AB  - Among retroviruses, lentiviruses are unusual in their ability to efficiently
      infect both dividing and nondividing cells, such as activated T cells and
      macrophages, respectively. Recent studies implicate the viral capsid protein (CA)
      as a key determinant of cell-cycle-independent infection by human
      immunodeficiency virus type 1 (HIV-1). We investigated the effects of the host
      cell protein cyclophilin A (CypA), which binds to HIV-1 CA, on HIV-1 infection of
      nondividing cells. The HIV-1 CA mutants A92E, T54A, and R132K were impaired for
      infection of aphidicolin-arrested HeLa cells, but not HOS cells. The mutants
      synthesized normal quantities of two-long-terminal-repeat circles in arrested
      HeLa cells, indicating that the mutant preintegration complexes can enter the
      nuclei of both dividing and nondividing cells. The impaired infectivity of the CA
      mutants on both dividing and nondividing HeLa cells was relieved by either
      pharmacological or genetic disruption of the CypA-CA interaction or by RNA
      interference-mediated depletion of CypA expression in target cells. A second-site
      suppressor of the CypA-restricted phenotype also restored the ability of CypA
      restricted HIV-1 mutants to infect growth-arrested HeLa cells. These results
      indicate that CypA-restricted mutants are specifically impaired at a step between
      nuclear import and integration in nondividing HeLa cells. This study reveals a
      novel target cell-specific restriction of HIV-1 CA mutants in nondividing cells
      that is dependent on CypA-CA interactions.

PMID- 18829763
TI  - Engineering viable foot-and-mouth disease viruses with increased thermostability
      as a step in the development of improved vaccines.
AB  - We have rationally engineered foot-and-mouth disease virus to increase its
      stability against thermal dissociation into subunits without disrupting the many
      biological functions needed for its infectivity. Amino acid side chains located
      near the capsid intersubunit interfaces and either predicted or found to be
      dispensable for infectivity were replaced by others that could establish new
      disulfide bonds or electrostatic interactions between subunits. Two engineered
      viruses were normally infectious, genetically stable, and antigenically
      indistinguishable from the natural virus but showed substantially increased
      stability against irreversible dissociation. Electrostatic interactions mediated
      this stabilizing effect. For foot-and-mouth disease virus and other viruses, some
      evidence had suggested that an increase in virion stability could be linked to an
      impairment of infectivity. The results of the present study show, in fact, that
      virion thermostability against dissociation into subunits may not be selectively
      constrained by functional requirements for infectivity. The thermostable viruses
      obtained, and others similarly engineered, could be used for the production,
      using current procedures, of foot-and-mouth disease vaccines that are less
      dependent on a faultless cold chain. In addition, introduction of those
      stabilizing mutations in empty (nucleic acid-free) capsids could facilitate the
      production of infection-risk-free vaccines against the disease, one of the
      economically most important animal diseases worldwide.

PMID- 18829764
TI  - Experimental evolution of human influenza virus H3 hemagglutinin in the mouse
      lung identifies adaptive regions in HA1 and HA2.
AB  - The genetic basis for virulence and host switching in influenza A viruses (FLUAV)
      is largely unknown. Because the hemagglutinin (HA) protein is a determinant of
      these properties, HA evolution was mapped in an experimental model of mouse lung
      adaptation. Variants of prototype A/Hong Kong/1/68 (H3N2) (wild-type [wt] HK)
      human virus were selected in both longitudinal and parallel studies of lung
      adaptation. Mapping of HA mutations found in 11 independently derived mouse
      adapted populations of wt HK identified 27 mutations that clustered within two
      distinct regions in or near the globular frameworks of the HA1 and HA2 subunits.
      The adaptive mutations demonstrated multiple instances of convergent evolution
      involving four amino acid positions (162, 210, and 218 in HA1 and 154 in HA2). By
      use of reverse genetics, convergent HA mutations were shown to affect cell
      tropism by enhancing infection and replication in primary mouse tracheal
      epithelial cells in vitro and mouse lung tissue in vivo. Adaptive HA mutations
      were multifunctional, affecting both median pH of fusion and receptor
      specificity. Specific mutations within both adaptive regions were shown to
      increase virulence in a mouse lung model. The occurrence of mutations in the HA1
      and HA2 adaptive regions of natural FLUAV host range and virulent variants of
      avian and mammalian viruses is discussed. This study has identified adaptive
      sites and regions within the HA1 and HA2 subunits that may guide future studies
      of viral adaptation and evolution in nature.

PMID- 18829765
TI  - Characterization of white spot syndrome virus envelope protein VP51A and its
      interaction with viral tegument protein VP26.
AB  - In this study, we characterize a novel white spot syndrome virus (WSSV)
      structural protein, VP51A (WSSV-TW open reading frame 294), identified from a
      previous mass spectrometry study. Temporal-transcription analysis showed that
      vp51A is expressed in the late stage of WSSV infection. Gene structure analysis
      showed that the transcription initiation site of vp51A was 135 bp upstream of the
      translation start codon. The poly(A) addition signal overlapped with the
      translation stop codon, TAA, and the poly(A) tail was 23 bp downstream of the
      TAA. Western blot analysis of viral protein fractions and immunoelectron
      microscopy both suggested that VP51A is a viral envelope protein. Western
      blotting of the total proteins extracted from WSSV virions detected a band that
      was close to the predicted 51-kDa mass, but the strongest signal was around 72
      kDa. We concluded that this 72-kDa band was in fact the full-length VP51A
      protein. Membrane topology assays demonstrated that the VP51A 72-kDa protein is a
      type II transmembrane protein with a highly hydrophobic transmembrane domain on
      its N terminus and a C terminus that is exposed on the surface of the virion.
      Coimmunoprecipitation, colocalization, and yeast two-hybrid assays revealed that
      VP51A associated directly with VP26 and indirectly with VP28, with VP26 acting as
      a linker protein in the formation of a VP51A-VP26-VP28 complex.

PMID- 18829767
TI  - Heparan sulfate-independent cell binding and infection with furin-precleaved
      papillomavirus capsids.
AB  - Papillomavirus infection normally involves virion binding to cell surface heparan
      sulfate proteoglycans (HSPGs). However, we found that human papillomavirus type
      16 pseudovirions efficiently bound and infected cells lacking HSPGs if their L2
      capsid protein was precleaved by furin, a cellular protease required for
      infection. The inability of pseudovirions to efficiently bind and infect cultured
      primary keratinocytes was also overcome by furin precleavage, suggesting that the
      defect involves altered HSPG modification. We conclude that the primary function
      of HSPG binding is to enable cell surface furin cleavage of L2 and that binding
      to a distinct cell surface receptor(s) is a subsequent step of papillomavirus
      infection.

PMID- 18829766
TI  - Kaposi's sarcoma-associated herpesvirus forms a multimolecular complex of
      integrins (alphaVbeta5, alphaVbeta3, and alpha3beta1) and CD98-xCT during
      infection of human dermal microvascular endothelial cells, and CD98-xCT is
      essential for the postentry stage of infection.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV) interacts with cell surface
      heparan sulfate (HS) and alpha3beta1 integrin during the early stages of
      infection of human dermal microvascular endothelial cells (HMVEC-d) and human
      foreskin fibroblasts (HFF), and these interactions are followed by virus entry
      overlapping with the induction of preexisting host cell signal pathways. KSHV
      also utilizes the amino acid transporter protein xCT for infection of adherent
      cells, and the xCT molecule is part of the cell surface heterodimeric membrane
      glycoprotein CD98 (4F2 antigen) complex known to interact with alpha3beta1 and
      alphaVbeta3 integrins. KSHV gB mediates adhesion of HMVEC-d, CV-1, and HT-1080
      cells and HFF via its RGD sequence. Anti-alphaV and -beta1 integrin antibodies
      inhibited the cell adhesion mediated by KSHV-gB. Variable levels of
      neutralization of HMVEC-d and HFF infection were observed with antibodies against
      alphaVbeta3 and alphaVbeta5 integrins. Similarly, variable levels of inhibition
      of virus entry into adherent HMVEC-d, 293 and Vero cells, and HFF was observed by
      preincubating virus with soluble alpha3beta1, alphaVbeta3, and alphaVbeta5
      integrins, and cumulative inhibition was observed with a combination of
      integrins. We were unable to infect HT1080 cells. Virus binding and DNA
      internalization studies suggest that alphaVbeta3 and alphaVbeta5 integrins also
      play roles in KSHV entry. We observed time-dependent temporal KSHV interactions
      with HMVEC-d integrins and CD98/xCT with three different patterns of association
      and dissociation. Integrin alphaVbeta5 interaction with CD98/xCT predominantly
      occurred by 1 min postinfection (p.i.) and dissociated at 10 min p.i., whereas
      alpha3beta1-CD98/xCT interaction was maximal at 10 min p.i. and dissociated at 30
      min p.i., and alphaVbeta3-CD98/xCT interaction was maximal at 10 min p.i. and
      remained at the observed 30 min p.i. Fluorescence microscopy also showed a
      similar time-dependent interaction of alphaVbeta5-CD98. Confocal-microscopy
      studies confirmed the association of CD98/xCT with alpha3beta1 and KSHV.
      Preincubation of KSHV with soluble heparin and alpha3beta1 significantly
      inhibited this association, suggesting that the first contact with HS and
      integrin is an essential element in subsequent CD98-xCT interactions. Anti-CD98
      and xCT antibodies did not block virus binding and entry and nuclear delivery of
      viral DNA; however, viral-gene expression was significantly inhibited, suggesting
      that CD98-xCT play roles in the post-entry stage of infection, possibly in
      mediating signal cascades essential for viral-gene expression. Together, these
      studies suggest that KSHV interacts with functionally related integrins
      (alphaVbeta3, alpha3beta1, and alphaVbeta5) and CD98/xCT molecules in a temporal
      fashion to form a multimolecular complex during the early stages of endothelial
      cell infection, probably mediating multiple roles in entry, signal transduction,
      and viral-gene expression.

PMID- 18829768
TI  - Selecting developmental surveillance and screening tools.

PMID- 18829769
TI  - Chronic kidney disease in children.

PMID- 18829770
TI  - Hematuria.

PMID- 18829771
TI  - Complementary, holistic, and integrative medicine: a review of therapies for
      diarrhea.

PMID- 18829772
TI  - Index of suspicion.

PMID- 18829773
TI  - A "vaccine" against violence: coping power.

PMID- 18829774
TI  - Fatherhood in adolescence.

PMID- 18829775
TI  - Safety on bicycles, skateboards, scooters, and skates.

PMID- 18829777
TI  - Experience of families during cardiopulmonary resuscitation in a pediatric
      intensive care unit.
AB  - OBJECTIVES: Having parents present during cardiopulmonary resuscitation is
      becoming a common practice in pediatrics. This study aimed to determine parents'
      perception of the effects of their presence during the resuscitation efforts of
      their child and whether they would recommend the experience to other families.
      METHODS: This study included parents or guardians of children who underwent
      cardiopulmonary resuscitation, and died at least 6 months before the interview.
      After telephone consent was obtained, a survey questionnaire was completed. The
      interviewees answered whether they were asked to be present, whether they had
      physical contact with their child, and whether the experience frightened them or
      gave them and their child comfort. The interviewees were asked to express their
      feelings about what was helpful to them and what could be done to improve the
      experience. RESULTS: A total of 41 interviews were conducted, and responders were
      divided into 2 groups: 21 in the present group and 20 in the not-present group
      for cardiopulmonary resuscitation. Twelve (60%) of those in the not-present group
      believed that their presence would have comforted the child, and 50% (10 of 20)
      believed that it would have helped them accept the child's death. Of those in the
      present group, 67% (8 of 12) believed that touching their child brought comfort,
      29% (6 of 21) felt scared during cardiopulmonary resuscitation, 71% (15 of 21)
      believed that their presence comforted their child, and 67% (14 of 21) believed
      that their presence helped them adjust to the loss of the child. The majority in
      both groups (63% [26 of 41]) would recommend being present during cardiopulmonary
      resuscitation. CONCLUSIONS: This study supports encouraging family presence
      during cardiopulmonary resuscitation. The majority of parents who had been
      present and those who had not been present believed that all families should be
      given the option to be present.

PMID- 18829776
TI  - Outcomes of safety and effectiveness in a multicenter randomized, controlled
      trial of whole-body hypothermia for neonatal hypoxic-ischemic encephalopathy.
AB  - BACKGROUND: Whole-body hypothermia reduced the frequency of death or
      moderate/severe disabilities in neonates with hypoxic-ischemic encephalopathy in
      a randomized, controlled multicenter trial. OBJECTIVE: Our goal was to evaluate
      outcomes of safety and effectiveness of hypothermia in infants up to 18 to 22
      months of age. DESIGN/METHODS: A priori outcomes were evaluated between
      hypothermia (n = 102) and control (n = 106) groups. RESULTS: Encephalopathy
      attributable to causes other than hypoxia-ischemia at birth was not noted.
      Inotropic support (hypothermia, 59% of infants; control, 56% of infants) was
      similar during the 72-hour study intervention period in both groups. Need for
      blood transfusions (hypothermia, 24%; control, 24%), platelet transfusions
      (hypothermia, 20%; control, 12%), and volume expanders (hypothermia, 54%;
      control, 49%) was similar in the 2 groups. Among infants with persistent
      pulmonary hypertension (hypothermia, 25%; control, 22%), nitric-oxide use
      (hypothermia, 68%; control, 57%) and placement on extracorporeal membrane
      oxygenation (hypothermia, 4%; control, 9%) was similar between the 2 groups. Non
      central nervous system organ dysfunctions occurred with similar frequency in the
      hypothermia (74%) and control (73%) groups. Rehospitalization occurred among 27%
      of the infants in the hypothermia group and 42% of infants in the control group.
      At 18 months, the hypothermia group had 24 deaths, 19 severe disabilities, and 2
      moderate disabilities, whereas the control group had 38 deaths, 25 severe
      disabilities, and 1 moderate disability. Growth parameters were similar between
      survivors. No adverse outcomes were noted among infants receiving hypothermia
      with transient reduction of temperature below a target of 33.5 degrees C at
      initiation of cooling. There was a trend in reduction of frequency of all
      outcomes in the hypothermia group compared with the control group in both
      moderate and severe encephalopathy categories. CONCLUSIONS: Although not powered
      to test these secondary outcomes, whole-body hypothermia in infants with
      encephalopathy was safe and was associated with a consistent trend for decreasing
      frequency of each of the components of disability.

PMID- 18829779
TI  - Elevated blood pressure in relation to overweight and obesity among children in a
      rural Canadian community.
AB  - OBJECTIVE: Childhood overweight and obesity may result in premature onset of
      cardiovascular risk factors such as hypertension. Rural populations in North
      America may be at increased risk for overweight. We evaluated whether overweight
      and obesity were associated with prehypertension and hypertension in a well
      characterized population of children in rural Canada. METHODS: The study
      population for this cross-sectional study was composed of children (aged 4-17
      years) who were participants of the Walkerton Health Study (Canada) in 2004.
      Prehypertension and hypertension were defined on the basis of percentiles from
      the average of 3 blood pressure measures taken on a single occasion. Percentiles
      for BMI and blood pressure were calculated by using the 2000 Centers for Disease
      Control and Prevention growth charts. Multinomial logistic regression was used to
      evaluate the odds for prehypertension and hypertension resulting from overweight
      and obesity. RESULTS: Of 675 children (98.7% white), 122 (18.1%) were overweight
      and 77 (11.4%) were obese. Prehypertension and hypertension were detected in 51
      (7.6%) and 50 (7.4%), respectively. After adjustment for family history of
      hypertension and kidney disease, obesity was associated with both prehypertension
      and hypertension. Overweight was associated with hypertension but not
      prehypertension. These associations were observed across the genders and children
      aged <13 and >or=13 years, except that overweight was not associated with
      hypertension among girls. CONCLUSIONS: In this population of children who lived
      in a rural community in Canada, overweight and obesity were strongly associated
      with elevated blood pressure. Whether blood pressure normalizes with improvements
      in diet, physical activity, and environment is an area for additional study.

PMID- 18829778
TI  - Linking mother and child access to dental care.
AB  - OBJECTIVES: Among young children in low-income families covered by Medicaid, we
      estimated (according to racial/ethnic group) whether children who have mothers
      with a regular source of dental care at baseline have greater dental use in the
      subsequent year than children with mothers without a regular source. METHODS:
      From a population of 108151 children (aged 3 to 6 years) who were enrolled in
      Medicaid and their low-income mothers in Washington state, a disproportionate
      stratified random sample of 11305 children aged 3 to 6 was selected from
      enrollment records in 4 racial/ethnic groups: black (3791), Hispanic (2806),
      white (1902), and other racial/ethnic groups (2806). In a prospective cohort
      design, we conducted a baseline survey of mothers and for respondents collected
      their children's Medicaid dental claims in the 1-year follow-up period.
      Mutivariable regression models estimated the associations between the mothers'
      having a regular source of dental care at baseline and their children's
      prospective dental use. RESULTS: Approximately 38% of the mothers had a regular
      source of dental care. Among children of black and Hispanic mothers, having a
      mother with a regular source of dental care at baseline was associated with
      greater odds of receiving any dental care in the subsequent year. For children
      with dental use, children of black or Hispanic mothers with a regular source of
      dental care received 1.22 and 1.10 more preventive services, respectively. For
      children of white mothers, associations were in the same direction but not
      significant. CONCLUSIONS: For young children of black and Hispanic mothers,
      dental care use is higher when their mothers have a regular source of dental
      care. For low-income young children with Medicaid, increasing the mothers' access
      to dental care may increase the children's use of dental and preventive services,
      which, in turn, may reduce racial/ethnic inequalities in oral health.

PMID- 18829780
TI  - Cardiovascular risk screening before starting stimulant medications and
      prescribing practices of canadian physicians: impact of the Health Canada
      advisory.
AB  - OBJECTIVE: In May 2006, Health Canada released a statement advising against the
      use of stimulant medications for patients with cardiac disease after isolated
      reports of sudden death. The objectives of this study were to determine whether
      the Health Canada advisory has had an impact on cardiovascular screening of all
      children with attention-deficit/hyperactivity disorder before stimulants and the
      medical treatment of children with attention-deficit/hyperactivity disorder and
      real or potential cardiac problems. METHODS: Two questionnaires were developed
      and mailed to a sample of noncardiologist physicians and pediatric cardiologists
      in Canada. The difference in the proportion of noncardiologist-responders who
      performed a "full screen" before and after the announcement of the Health Canada
      advisory was analyzed. Willingness to prescribe stimulant medications to children
      was assessed by using a series of clinical scenarios. RESULTS: A total of 2326
      questionnaires were distributed, 717 (31%) of which were returned. The proportion
      who performed a full screen increased for both noncardiologists and cardiologists
      after the advisory. There was also a dramatic increase in the use of the
      "modified screen" by the noncardiologist group and the pediatrician subgroup.
      There was a considerable decrease in the proportion of noncardiologists who were
      willing to prescribe stimulant medications to children with potential or actual
      cardiac issues after the advisory. CONCLUSIONS: The Health Canada advisory has
      had an impact on clinical practice. It has resulted in an increase in the use of
      cardiovascular assessment tools before starting stimulants and a decrease in
      noncardiologists' willingness to prescribe stimulants to those with real or
      potential cardiac disease. These changes have occurred despite the lack of
      studies to address the cardiac risks of these medications. Because it will be
      difficult to assess the true cardiac risks of stimulants, consensus
      recommendations are needed to determine whether screening is required, what
      constitutes an appropriate screen, and which children can be treated cautiously
      with stimulant medications.

PMID- 18829781
TI  - Temporary vaccine recommendations and provider compliance: a survey of pediatric
      practices during the 2003-2004 pneumococcal conjugate vaccine shortage.
AB  - OBJECTIVE: Heptavalent pneumococcal conjugate vaccine was in short supply from
      December 2003 to August 2004. The Centers for Disease Control and Prevention with
      the American Academy of Pediatrics and the American Academy of Family Physicians
      made recommendations to providers to withhold third and fourth doses of
      heptavalent pneumococcal conjugate vaccine to ensure availability for those at
      highest risk. Previous studies of vaccine shortages have demonstrated that
      provider compliance with temporary recommendations is low. The objective of this
      study was to collect timely data about awareness and adherence to temporary
      recommendations and current supply status of heptavalent pneumococcal conjugate
      vaccine in pediatric practices. METHODS: A 2-phase telephone survey of pediatric
      practices was conducted during a 10-week period during the 2003-2004 heptavalent
      pneumococcal conjugate vaccine shortage. Immunization nurses at randomly selected
      sites with physician-members of the American Academy of Pediatrics were asked a
      series of questions. RESULTS: In both study phases, >90% of participating
      practices were aware of the recommendations and reported adhering to the
      recommendations. In phase 1, practices with insufficient supply were more likely
      to implement recommendations than practices with sufficient supply. Participants
      identified health departments and Wyeth Vaccines as the most common sources of
      information. At least 65% of the practices in each phase reported use of tracking
      systems for children who missed doses. CONCLUSIONS: Most pediatric practices
      surveyed were aware of the shortage and were implementing the heptavalent
      pneumococcal conjugate vaccine recommendations. Simplified recommendations and
      collaborative efforts to develop and widely disseminate interim recommendations
      may result in increased compliance by providers.

PMID- 18829782
TI  - Skin conductance versus the modified COMFORT sedation score as a measure of
      discomfort in artificially ventilated children.
AB  - OBJECTIVE: We wanted to use skin conductance as a measure of increased stress in
      artificially ventilated children. The aim was to examine how changes in skin
      conductance, arterial blood pressure, and heart rate are associated with changes
      in the modified COMFORT sedation score during suction from the trachea.
      Nociceptive stimulation induces an outgoing sympathetic nervous burst to the skin
      and the palmar and plantar sweat glands are filled, which creates a skin
      conductance fluctuation. METHODS: Twenty children who were 1 day to 11 years of
      age were studied. All patients were artificially ventilated and circulatory
      stable. The data were obtained before, during, and 10 minutes after endotracheal
      suction. The number of skin conductance fluctuations, the amplitude of skin
      conductance fluctuations, the mean skin conductance level, arterial blood
      pressure, heart rate, and the modified COMFORT sedation score were recorded and
      tested from before to during and from during to after suction in the trachea.
      RESULTS. The number of skin conductance fluctuations, mean skin conductance
      level, arterial blood pressure, and the modified COMFORT sedation score increased
      during suction in the trachea, in contrast to heart rate and amplitude of skin
      conductance fluctuations. The number of skin conductance fluctuations from before
      to during and from during to after endotracheal suctioning correlated with
      changes in the modified COMFORT sedation score. This was in contrast to the other
      variables that did not. CONCLUSIONS: The number of skin conductance fluctuations
      during endotracheal suctioning showed better correlation with the increase in the
      modified COMFORT sedation score than heart rate and arterial blood pressure.
      Thus, the number of skin conductance fluctuations seems to be an objective
      supplement to the modified COMFORT sedation score for monitoring increased stress
      in artificially ventilated and circulatory stable children.

PMID- 18829783
TI  - Food insecurity and compensatory feeding practices among urban black families.
AB  - OBJECTIVE: In this we study explored the relationship between food insecurity and
      compensatory maternal feeding practices that may be perceived as buffers against
      periodic food shortages among urban black families. METHODS: We interviewed a
      convenience sample of black mothers of children aged 2 to 13 years. Food-security
      status (predictor) was determined at the household level. Five maternal feeding
      practices (outcomes) were assessed. Two were based on Birch's Child Feeding
      Questionnaire (restricting access to certain foods and pressuring a child to
      eat), and 3 were derived from investigators' clinical experience (use of high
      energy supplements, added sugar in beverages, and perceived appetite stimulants).
      Anthropometric data were collected from mothers and children. RESULTS: A total of
      278 mother-child dyads were analyzed, and 28% of these mothers reported being
      food insecure. Use of Child Feeding Questionnaire feeding practices was defined
      as the top quartile of responses. Use of nutritional supplements, defined as "at
      least 1 to 2 times monthly," ranged from 13% to 25%. In logistic regression
      models adjusted for child age, weight status, and ethnicity and maternal weight
      status, mothers from food-insecure households were significantly more likely to
      use high-energy supplements and appetite stimulants. The odds of using the
      remaining compensatory feeding practices (adding sugars to beverages, pressuring
      a child to eat, and restricting access to certain foods) were elevated among food
      insecure households but did not reach statistical significance. CONCLUSIONS:
      Household food insecurity was independently associated with 2 of the 5 maternal
      compensatory feeding practices studied, and such practices may alter the feeding
      environment. Longitudinal research is necessary to determine how the relationship
      between food security and compensatory maternal feeding practices may affect
      child weight trajectories.

PMID- 18829784
TI  - An intervention to decrease narcotic-related adverse drug events in children's
      hospitals.
AB  - OBJECTIVES: Narcotic-related adverse drug events are the most common adverse drug
      events in hospitalized children. Despite multiple published studies describing
      interventions that decrease adverse drug events from narcotics, large-scale
      collaborative quality improvement efforts to address narcotic-related adverse
      drug events in pediatrics have not been described. The purpose of this study was
      to evaluate collaborative-wide narcotic-related adverse drug event rates after a
      collection of expert panel-defined best practices was implemented. METHODS: All
      42 children's hospitals in the Child Health Corporation of America were invited
      to participate in the Institute for Healthcare Improvement-style quality
      improvement collaborative aimed at reducing narcotic-related adverse drug events.
      A collection of interventions known or suspected to reduce narcotic-related
      adverse drug events was recommended by an expert panel, with each site
      implementing >or=1 of these best practices on the basis of local need. Narcotic
      related adverse drug event rates were compared between the baseline (December 1,
      2004, to March 31, 2005) and postimplementation periods (January 1, 2006, to
      March 31, 2006) after an a priori-defined intervention ramp-up time (April 1,
      2005, and December 31, 2005). Secondary outcome measures included constipation
      rates and narcotic-related automated drug-dispensing-device override percentages.
      RESULTS: Median narcotic-related adverse drug event rates decreased 67% between
      the baseline and postimplementation time frames across the 14-site collaborative.
      Constipation rates decreased 68.9%, and automated drug-dispensing-device
      overrides decreased from 10.18% to 5.91% of all narcotic doses administered.
      CONCLUSIONS: Implementation of >or=1 expert panel-recommended interventions at
      each participating site resulted in a significant decrease in narcotic-related
      adverse drug events, constipation, and automated drug-dispensing-device overrides
      in a 12-month, 14-site children's hospital quality collaborative.

PMID- 18829785
TI  - A brief indicator of household energy security: associations with food security,
      child health, and child development in US infants and toddlers.
AB  - OBJECTIVE: Household energy security has not been measured empirically or related
      to child health and development but is an emerging concern for clinicians and
      researchers as energy costs increase. The objectives of this study were to
      develop a clinical indicator of household energy security and assess associations
      with food security, health, and developmental risk in children <36 months of age.
      METHODS: A cross-sectional study that used household survey and surveillance data
      was conducted. Caregivers were interviewed in emergency departments and primary
      care clinics form January 2001 through December 2006 on demographics, public
      assistance, food security, experience with heating/cooling and utilities, Parents
      Evaluation of Developmental Status, and child health. The household energy
      security indicator includes energy-secure, no energy problems; moderate energy
      insecurity, utility shutoff threatened in past year; and severe energy
      insecurity, heated with cooking stove, utility shutoff, or >or=1 day without
      heat/cooling in past year. The main outcome measures were household and child
      food security, child reported health status, Parents Evaluation of Developmental
      Status concerns, and hospitalizations. RESULTS: Of 9721 children, 11% (n = 1043)
      and 23% (n = 2293) experienced moderate and severe energy insecurity,
      respectively. Versus children with energy security, children with moderate energy
      insecurity had greater odds of household food insecurity, child food insecurity,
      hospitalization since birth, and caregiver report of child fair/poor health,
      adjusted for research site and mother, child, and household characteristics.
      Children with severe energy insecurity had greater adjusted odds of household
      food insecurity, child food insecurity, caregivers reporting significant
      developmental concerns on the Parents Evaluation of Developmental Status scale,
      and report of child fair/poor health. No significant association was found
      between energy security and child weight for age or weight for length.
      CONCLUSIONS: As household energy insecurity increases, infants and toddlers
      experienced increased odds of household and child food insecurity and of reported
      poor health, hospitalizations, and developmental risks.

PMID- 18829786
TI  - Growth patterns and obesity development in overweight or normal-weight 13-year
      old adolescents: the STRIP study.
AB  - OBJECTIVE: Our goal was to study childhood growth patterns and development of
      overweight in children who were overweight or normal weight at 13 years of age.
      PARTICIPANTS AND METHODS: This study is part of a prospective atherosclerosis
      prevention trial Special Turku Coronary Risk Factor Intervention Project for
      Children). At 7 months of age, 1062 children were randomly assigned to an
      intervention group (n = 540) receiving biannual fat-oriented dietary counseling
      or to a control group (n = 522). Height and weight of the children and their
      parents were monitored annually. Our study group comprised those children who
      participated in the 13-year study visit (n = 541). At 13 years of age, the child
      was classified as overweight (n = 84) if his or her BMI exceeded the
      international age- and gender-specific overweight criteria. RESULTS: In
      overweight girls, the annual weight gain increased from 2.8 kg during the third
      and fourth year of life to 7.5 kg during the 12th year of life, whereas the
      annual weight gain of the girls who were normal weight ranged from 2.1 to 4.8 kg
      during the same period. The annual weight gain was similar of overweight boys and
      in their normal-weight peers until the age of 5 years, but after that it
      increased from 3.5 to 7.9 kg in overweight and from 2.6 to 5.5 kg in normal
      weight boys. The BMI of the girls and boys who were overweight at the age of 13
      exceeded the international cutoff point for overweight from the age of 5 and 8
      years onward, respectively. The mean BMIs of the mothers and fathers of the
      overweight children were higher than those of the parents of the normal-weight
      children. The STRIP intervention had no effect on the examined growth parameters
      or on parental BMI. CONCLUSIONS: The children who were overweight at 13 years of
      age gained more weight than their normal-weight peers by the age of 2 or 3 years
      onward. The girls became overweight by the age of 5 years, whereas the boys only
      after 8 years of age. Parental BMI and steep weight gain in early childhood
      indicate markedly increased risk for becoming overweight.

PMID- 18829787
TI  - Preauricular skin tags and ear pits are associated with permanent hearing
      impairment in newborns.
AB  - OBJECTIVES: Our goals were to (1) study the prevalence of hearing impairment in a
      large cohort of infants with preauricular skin tags or ear pits and compare it
      with that among all other newborns participating in our universal newborn hearing
      screening program during the same period and (2) evaluate the effectiveness of
      transient evoked otoacoustic emissions as a hearing-screening tool in this
      population. PATIENTS AND METHODS: During the study period of 7.5 years, 68484
      infants were screened for hearing impairment, of whom 637 (0.93%) had
      preauricular skin tags and/or ear pits. The population was divided into 3 groups:
      (1) a low-risk group for hearing impairment; (2) a high-risk group for hearing
      impairment; and (3) a very high-risk group for hearing impairment. The screening
      results and audiological follow-up for these infants were examined
      retrospectively. RESULTS: A significantly higher prevalence of permanent hearing
      impairment was found among infants with preauricular skin tags or ear pits (8 of
      1000), compared with infants without tags or pits (1.5 of 1000). In the low-risk
      group, the prevalence was 3.4 of 1000, compared with 0.5 of 1000 in infants with
      and without preauricular tags or pits, respectively. In the high-risk group, the
      prevalence was 77 of 1000, compared with 20 of 1000 in infants with and without
      preauricular tags or pits, respectively. The odds ratio for hearing impairment
      associated with preauricular skin tags and/or ear pits after adjusting for level
      of risk group was 4.9. All infants diagnosed with permanent hearing impairment,
      with the exception of 1 with late-onset impairment, were detected by in-hospital
      transient-evoked otoacoustic emissions screening. CONCLUSIONS: Infants with
      preauricular skin tags or ear pits are at increased risk for permanent hearing
      impairment. Transient-evoked otoacoustic emissions were found to be an effective
      hearing-screening tool in this population.

PMID- 18829788
TI  - A review of the evidence for the medical home for children with special health
      care needs.
AB  - CONTEXT: The receipt of health care in a medical home is increasingly touted as a
      fundamental basis for improved care for persons with chronic conditions, yet the
      evidence for this claim has not been systematically assessed. OBJECTIVE: Our goal
      was to determine the evidence for the federal Maternal and Child Health Bureau
      recommendation that children with special health care needs receive ongoing
      comprehensive care within a medical home. METHODS: We searched the nursing and
      medical literature, references of selected articles, and requested expert
      recommendations. Search terms included children with special health care needs,
      medical home-related interventions, and health-related outcomes. Articles that
      met defined criteria (eg, children with special health care needs, United States
      based, quantitative) were selected. We extracted data, including design,
      population characteristics, sample size, intervention, and findings from each
      article. RESULTS: We selected 33 articles that reported on 30 distinct studies,
      10 of which were comparison-group studies. None of the studies examined the
      medical home in its entirety. Although tempered by weak designs, inconsistent
      definitions and extent of medical home attributes, and inconsistent outcome
      measures, the preponderance of evidence supported a positive relationship between
      the medical home and desired outcomes, such as better health status, timeliness
      of care, family centeredness, and improved family functioning. CONCLUSIONS: The
      evidence provides moderate support for the hypothesis that medical homes provide
      improved health-related outcomes for children with special health care needs.
      Additional studies with comparison groups encompassing all or most of the
      attributes of the medical home need to be undertaken.

PMID- 18829789
TI  - Severe cardiovascular and thromboembolic consequences of pneumococcal infection
      in a child.
AB  - We present an unusually severe case of pneumococcal infection in an
      immunocompetent child who progressed from pneumonia to empyema, pericarditis with
      cardiac tamponade, and severe venous thromboembolism leading to life-threatening
      pulmonary embolus.

PMID- 18829790
TI  - Oral probiotics prevent necrotizing enterocolitis in very low birth weight
      preterm infants: a multicenter, randomized, controlled trial.
AB  - OBJECTIVE: The goal was to investigate the efficacy of orally administered
      probiotics in preventing necrotizing enterocolitis for very low birth weight
      preterm infants. METHODS: A prospective, blinded, randomized, multicenter
      controlled trial was conducted at 7 NICUs in Taiwan, to evaluate the beneficial
      effects of probiotics in necrotizing enterocolitis among very low birth weight
      infants (birth weight: <1500 g). Very low birth weight infants who survived to
      start enteral feeding were eligible and were assigned randomly to 2 groups after
      parental informed consent was obtained. Infants in the study group were given
      Bifidobacterium bifidum and Lactobacillus acidophilus, added to breast milk or
      mixed feeding (breast milk and formula), twice daily for 6 weeks. Infants in the
      control group were fed with breast milk or mixed feeding. The clinicians caring
      for the infants were blinded to the group assignment. The primary outcome
      measurement was death or necrotizing enterocolitis (Bell's stage >or=2). RESULTS:
      Four hundred thirty-four infants were enrolled, 217 in the study group and 217 in
      the control group. The incidence of death or necrotizing enterocolitis (stage
      >or=2) was significantly lower in the study group (4 of 217 infants vs 20 of 217
      infants). The incidence of necrotizing enterocolitis (stage >or=2) was lower in
      the study group, compared with the control group (4 of 217 infants vs 14 of 217
      infants). No adverse effect, such as sepsis, flatulence, or diarrhea, was noted.
      CONCLUSION: Probiotics, in the form of Bifidobacterium and Lactobacillus, fed
      enterally to very low birth weight preterm infants for 6 weeks reduced the
      incidence of death or necrotizing enterocolitis.

PMID- 18829791
TI  - Procalcitonin in young febrile infants for the detection of serious bacterial
      infections.
AB  - OBJECTIVES: The objectives of the study were (1) to study the test performance of
      procalcitonin for identifying serious bacterial infections in febrile infants
      <or=90 days of age without an identifiable bacterial source and (2) to determine
      an optimal cutoff value to identify infants at low risk for serious bacterial
      infections. METHODS: A prospective observational study was performed with febrile
      infants <or=90 days of age presenting to an urban, pediatric, emergency
      department. Serum procalcitonin levels were measured by using an automated high
      sensitivity assay. An optimal procalcitonin cutoff value was selected to maximize
      sensitivity and negative predictive value for the detection of serious bacterial
      infections. Infants were classified as having definite, possible, or no serious
      bacterial infections. RESULTS: A total of 234 infants (median age: 51 days) were
      studied. Thirty infants (12.8%) had definite serious bacterial infections
      (bacteremia: n = 4; bacteremia with urinary tract infections: n = 2; urinary
      tract infections: n = 24), and 12 infants (5.1%) had possible serious bacterial
      infections (pneumonia: n = 5; urinary tract infections: n = 7). Mean
      procalcitonin levels for definite serious bacterial infections (2.21 +/- 3.9
      ng/mL) and definite plus possible serious bacterial infections (2.48 +/- 4.6
      ng/mL) were significantly higher than that for no serious bacterial infection
      (0.38 +/- 1.0 ng/mL). The area under the receiver operating characteristic curve
      was 0.82 for definite serious bacterial infections and 0.76 for definite and
      possible serious bacterial infections. For identifying definite and possible
      serious bacterial infections, a cutoff value of 0.12 ng/mL had sensitivity of
      95.2%, specificity of 25.5%, negative predictive value of 96.1%, and negative
      likelihood ratio of 0.19; all cases of bacteremia were identified accurately with
      this cutoff value. CONCLUSIONS: Procalcitonin has favorable test characteristics
      for detecting serious bacterial infections in young febrile infants.
      Procalcitonin measurements performed especially well in detecting the most
      serious occult infections.

PMID- 18829792
TI  - Adolescent immunizations: missed opportunities for prevention.
AB  - OBJECTIVES: The goals were (1) to describe immunization rates for tetanus
      diphtheria, hepatitis B, and measles-mumps-rubella vaccines among 13-year-old
      adolescents; (2) to identify missed opportunities for tetanus-diphtheria
      immunization among adolescents 11 to 17 years of age; and (3) to evaluate the
      association between preventive care use and tetanus-diphtheria immunization.
      METHODS: Adolescents born between January 1, 1986, and December 31, 1991, and
      enrolled in Harvard Pilgrim Health Care and Harvard Vanguard Medical Associates
      for >or=1 year in 1997-2004 were included. Immunization rates for tetanus
      diphtheria, hepatitis B, and measles-mumps-rubella were assessed at 13 years of
      age. Missed opportunities for tetanus-diphtheria immunization within 14 days
      after a health care visit were measured. Multivariate models were used to
      determine predictors of timeliness of tetanus-diphtheria vaccination,
      particularly the use of preventive care services. RESULTS. A total of 23,987
      eligible adolescents were enrolled in Harvard Pilgrim Health Care and Harvard
      Vanguard Medical Associates between 1997 and 2004. Among 13-year-old adolescents
      in the most recent birth cohort, 84%, 74%, and 67% were up to date for tetanus
      diphtheria, hepatitis B, and measles-mumps-rubella, respectively. When the
      analysis was limited to those with >or=1 vaccine received before 2 years of age
      (a proxy measure for complete records), 92%, 82%, and 85% were up to date for
      tetanus-diphtheria, hepatitis B, and measles-mumps-rubella, respectively. Missed
      opportunities for tetanus-diphtheria immunization occurred at 84% of all health
      care visits. Adolescents who did not seek preventive care were less likely to
      receive tetanus-diphtheria in a timely manner. CONCLUSIONS: Adolescent
      immunization rates lag far behind childhood rates, and missed opportunities are
      common. Additional strategies are needed to increase the use of preventive
      services among adolescents and to enable providers to vaccinate adolescents at
      every opportunity.

PMID- 18829793
TI  - Parents with doubts about vaccines: which vaccines and reasons why.
AB  - OBJECTIVES: The goals were (1) to obtain national estimates of the proportions of
      parents with indicators of vaccine doubt, (2) to identify factors associated with
      those parents, compared with parents reporting no vaccine doubt indicators, (3)
      to identify the specific vaccines that prompted doubt and the reasons why, and
      (4) to describe the main reasons parents changed their minds about delaying or
      refusing a vaccine for their child. METHODS: Data were from the National
      Immunization Survey (2003-2004). Groups included parents who ever got a
      vaccination for their child although they were not sure it was the best thing to
      do ("unsure"), delayed a vaccination for their child ("delayed"), or decided not
      to have their child get a vaccination ("refused"). RESULTS: A total of 3924
      interviews were completed. Response rates were 57.9% in 2003 and 65.0% in 2004.
      Twenty-eight percent of parents responded yes to ever experiencing >or=1 of the
      outcome measures listed above. In separate analyses for each outcome measure,
      vaccine safety concern was a predictor for unsure, refused, and delayed parents.
      The largest proportions of unsure and refused parents chose varicella vaccine as
      the vaccine prompting their concern, whereas delayed parents most often reported
      "not a specific vaccine" as the vaccine prompting their concern. Most parents who
      delayed vaccines for their child did so for reasons related to their child's
      illness, unlike the unsure and refused parents. The largest proportion of parents
      who changed their minds about delaying or not getting a vaccination for their
      child listed "information or assurances from health care provider" as the main
      reason. CONCLUSIONS: Parents who exhibit doubts about immunizations are not all
      the same. This research suggests encouraging children's health care providers to
      solicit questions about vaccines, to establish a trusting relationship, and to
      provide appropriate educational materials to parents.

PMID- 18829794
TI  - Effect of antibiotic pretreatment on cerebrospinal fluid profiles of children
      with bacterial meningitis.
AB  - OBJECTIVE: The goal of this study was to evaluate the effect of antibiotic
      administration before lumbar puncture on cerebrospinal fluid profiles in children
      with bacterial meningitis. METHODS: We reviewed the medical records of all
      children (1 month to 18 years of age) with bacterial meningitis who presented to
      20 pediatric emergency departments between 2001 and 2004. Bacterial meningitis
      was defined by positive cerebrospinal fluid culture results for a bacterial
      pathogen or cerebrospinal fluid pleocytosis with positive blood culture and/or
      cerebrospinal fluid latex agglutination results. Probable bacterial meningitis
      was defined as positive cerebrospinal fluid Gram stain results with negative
      results of bacterial cultures of blood and cerebrospinal fluid. Antibiotic
      pretreatment was defined as any antibiotic administered within 72 hours before
      the lumbar puncture. RESULTS: We identified 231 patients with bacterial
      meningitis and another 14 with probable bacterial meningitis. Of those 245
      patients, 85 (35%) had received antibiotic pretreatment. After adjustment for
      patient age, duration and severity of illness at presentation, and bacterial
      pathogen, longer duration of antibiotic pretreatment was not significantly
      associated with cerebrospinal fluid white blood cell count, cerebrospinal fluid
      absolute neutrophil count. However, antibiotic pretreatment was significantly
      associated with higher cerebrospinal fluid glucose and lower cerebrospinal fluid
      protein levels. Although these effects became apparent earlier, patients with
      >or=12 hours of pretreatment, compared with patients who either were not
      pretreated or were pretreated for <12 hours, had significantly higher median
      cerebrospinal fluid glucose levels (48 mg/dL vs 29 mg/dL) and lower median
      cerebrospinal fluid protein levels (121 vs 178 mg/dL). CONCLUSIONS: In patients
      with bacterial meningitis, antibiotic pretreatment is associated with higher
      cerebrospinal fluid glucose levels and lower cerebrospinal fluid protein levels,
      although pretreatment does not modify cerebrospinal fluid white blood cell count
      or absolute neutrophil count results.

PMID- 18829795
TI  - Prophylactic phenobarbital administration after resolution of neonatal seizures:
      survey of current practice.
AB  - OBJECTIVE: Child neurologists and neonatologists often discharge newborn infants
      with phenobarbital treatment for weeks to months despite the absence of
      continuing seizure activity. We conducted a national survey to determine the
      degree of variation in this practice. METHODS: Surveys were sent to a randomly
      generated list of board-certified child neurologists (N = 609) and neonatologists
      (N = 579). The survey consisted of 3 parts, that is, questions related to overall
      attitudes and practices, specific patient scenarios, and respondent demographic
      characteristics. Responses were tabulated and analyzed for all respondents
      combined and for child neurologists and neonatologists separately. Variation in
      practices between respondents and the consistency between the respondents' stated
      use of phenobarbital in practice and their answers to various clinical scenarios
      were evaluated. RESULTS: Responses were received from 118 child neurologists
      (20.7%) and 125 neonatologists (23.1%). There was wide variation in practices,
      with little difference in the response frequencies between child neurologists and
      neonatologists. Physicians were more likely to respond yes to continuation of
      phenobarbital treatment in a given clinical situation than would be predicted on
      the basis of their answers regarding overall frequency of use. CONCLUSIONS: Since
      the survey of practices 15 years ago, child neurologists and neonatologists are
      reporting less frequent and shorter phenobarbital treatment after resolution of
      neonatal seizures, although there remains considerable variation in practices.
      Moreover, what physicians report as their practice in general is inconsistent
      with how they respond to specific clinical cases of neonatal seizures.

PMID- 18829797
TI  - Randomized trial of very low birth weight infants receiving higher rates of
      infusion of intravenous fat emulsions during the first week of life.
AB  - OBJECTIVE: The goal was to determine whether very low birth weight infants could
      tolerate higher rates of infusion of intravenous fat emulsion during the first
      week of life and maintain their serum triglyceride levels at <or=200 mg/dL.
      METHODS: This was a randomized, controlled trial of 110 infants who were
      classified as appropriate for gestational age and had birth weights between 750 g
      and 1500 g. The primary clinical outcome was serum triglyceride levels; secondary
      outcomes also were monitored. RESULTS: One hundred infants completed the study
      (experimental group: N = 48; control group: N = 52). Infants in the experimental
      group had significantly higher energy intake for the entire 7-day study period
      and achieved 90 kcal/kg per day (1 kcal = 4.184 kJ) significantly sooner (7.38 +/
      3.381 days vs 9.44 +/- 3.578 days). Triglyceride levels for infants in the
      experimental group remained significantly higher for the first 5 days of life.
      Fifteen percent of infants in the experimental group but only 4% of infants in
      the control group developed hypertriglyceridemia. Ten percent of infants in the
      control group but no infants in the experimental group required insulin therapy.
      Forty-two percent of infants in the experimental group and 17% of infants in the
      control group remained at >or=10th percentile for weight for age. Fourteen
      percent of infants in the control group but no infants in the experimental group
      developed necrotizing enterocolitis. Twenty-three percent of infants in the
      control group but only 6% of infants in the experimental group developed
      retinopathy of prematurity. There were no significant differences in other
      outcomes. CONCLUSIONS: Very low birth weight infants can tolerate higher rates of
      infusion of intravenous fat emulsion solutions during the first week of life
      without significant adverse events.

PMID- 18829796
TI  - Free drug samples in the United States: characteristics of pediatric recipients
      and safety concerns.
AB  - OBJECTIVES: Free drug samples frequently are given to children. We sought to
      describe characteristics of free sample recipients, to determine whether samples
      are given primarily to poor and uninsured children, and to examine potential
      safety issues. METHODS: We analyzed data on 10295 US residents <18 years of age
      from the 2004 Medical Expenditure Panel Survey, a nationally representative
      survey that includes questions on receipt of free drug samples. We performed
      bivariate and multivariate analyses to evaluate characteristics associated with
      receipt of >or=1 free drug sample in 2004. We identified the most frequently
      reported sample medications and reviewed potential safety issues. RESULTS: Ten
      percent of children who received prescription medications and 4.9% of all
      children received >or=1 free drug sample in 2004. In bivariate analyses, poor
      children (family incomes of <200% of the federal poverty level) were no more
      likely to receive free samples than were those with incomes of >or=400% of the
      poverty level (3.8% vs 5.9%). Children who were uninsured for part or all of the
      year were no more likely to receive free samples than were those who were insured
      all year (4.5% vs 5.1%); 84.3% of all sample recipients were insured. In
      multivariate analyses, routine access to health care (>or=3 provider visits in
      2004) was associated with free sample receipt. The 15 most frequently distributed
      pediatric free samples in 2004 included 2 schedule II controlled medication,
      Adderall (amphetamine/dextroamphetamine) [corrected] and 4 medications that
      received new or revised black box warnings between 2004 and 2007, Elidel
      (pimecrolimus), Advair (fluticasone/salmeterol), Strattera (atomoxetine), and
      Adderall (amphetamine/dextroamphetamine). CONCLUSIONS: Poor and uninsured
      children are not the main recipients of free drug samples. Free samples do not
      target the neediest children selectively, and they have significant safety
      considerations.

PMID- 18829798
TI  - Distinct hemodynamic patterns of septic shock at presentation to pediatric
      intensive care.
AB  - OBJECTIVE: Early aggressive resuscitation is accepted best practice for severe
      pediatric sepsis. Targeting of therapy to individual hemodynamic patterns is
      recommended, but assessment of patterns is difficult early in the disease
      process. New technologies enabling earlier hemodynamic assessment in shock may
      inform choices for vasoactive drugs in fluid-resistant cases. METHODS: This was a
      prospective observational study of 30 children with suspected fluid-resistant
      septic shock (minimum: 40 mL/kg) admitted to the PICU of a tertiary care
      children's hospital between July 2004 and July 2005. Children were classified
      according to admission diagnosis (community-acquired sepsis or central venous
      catheter-associated infection) and assessed within 4 hours after the onset of
      shock with a noninvasive cardiac output device. Cardiac index and systemic
      vascular resistance index were measured for all patients. Central venous oxygen
      saturation was measured for patients with accessible central venous lines at the
      time of hemodynamic measurements (typically at the superior vena cava-right
      atrium junction). RESULTS: Fluid-resistant septic shock secondary to central
      venous catheter-associated infection was typically "warm shock" (15 of 16
      patients; 94%), with high cardiac index and low systemic vascular resistance
      index. In contrast, this pattern was rarely seen in community-acquired sepsis (2
      of 14 patients; 14%), where a normal or low cardiac index was predominant.
      CONCLUSIONS: The hemodynamic patterns of fluid-resistant septic shock by the time
      children present to the PICU are distinct, depending on cause, with little
      overlap. If these findings can be reproduced, then targeting the choice of first
      line vasoactive infusions in fluid-resistant shock (vasopressors for central
      venous catheter-associated infections and inotropes for community-acquired
      sepsis) should be considered.

PMID- 18829799
TI  - Modifiable risk factors for suboptimal control and controller medication underuse
      among children with asthma.
AB  - OBJECTIVES: Our aims were (1) to describe rates of suboptimal control and
      controller medication underuse in a diverse population of children with asthma
      and (2) to identify potentially modifiable parental behaviors and beliefs
      associated with these outcomes. METHODS: We conducted telephone interviews with
      parents of 2- to 12-year-old children with persistent asthma, in a Medicaid plan
      and a large provider group. Suboptimal control was defined as >or=4 symptom days,
      >or=1 symptom night, or >or=4 albuterol use days in the previous 2 weeks.
      Controller medication underuse was defined as suboptimal control and parent
      report of <6 days/week of inhaled steroid use. Multivariate analyses identified
      factors that were independently associated with suboptimal control and controller
      medication underuse. RESULTS: Of the 754 study children, 280 (37%) had suboptimal
      asthma control; this problem was more common in Hispanic children (51%) than in
      black (37%) or white (32%) children. Controller medication underuse was present
      for 133 children (48% of those with suboptimal asthma control and 18% overall).
      Controller medication underuse was more common among Hispanic (44%) and black
      (34%) children than white (22%) children. In multivariate analyses, suboptimal
      control was associated with potentially modifiable factors including low parental
      expectations for symptom control and high levels of worry about competing
      household priorities. Controller medication underuse was associated with
      potentially modifiable factors including parental estimation of asthma control
      that was discordant with national guidelines and no set time to administer asthma
      medications. CONCLUSIONS: Deficiencies in asthma control and controller
      medication use are associated with potentially modifiable parental beliefs, which
      seem to mediate racial/ethnic and socioeconomic disparities in suboptimal control
      and controller medication underuse.

PMID- 18829800
TI  - Randomized, controlled trial on tracheal colonization of ventilated infants: can
      gravity prevent ventilator-associated pneumonia?
AB  - OBJECTIVE: The goal was to test the hypothesis that intubated infants positioned
      on their sides would be less likely to contract bacterial colonization in their
      tracheae, compared with those positioned supine. METHODS: We conducted a
      prospective, randomized, controlled trial with 60 intubated infants; 30 infants
      were positioned supine (supine group), and 30 infants were maintained in the
      lateral position (lateral group). Tracheal aspirates were cultured and bacterial
      colony counts were recorded after 48 hours and after 5 days of mechanical
      ventilation. RESULTS: After 2 days, the numbers of positive tracheal cultures in
      the supine group (67%) and in the lateral group (47%) showed no statistical
      difference. After 5 days of mechanical ventilation, tracheal cultures differed
      significantly between groups. Cultures were positive for 26 infants (87%) in the
      supine group and 9 infants (30%) in the lateral group. Compared with the lateral
      group, more infants in the supine group experienced increased colony counts or
      had new organisms in their tracheal aspirates over time (21 vs 8 infants). The
      most common organisms isolated from tracheal aspirates in both groups were Gram
      negative rods. CONCLUSIONS: Respiratory contamination is very common among
      ventilated infants. Therefore, judicious use of mechanical ventilation cannot be
      overemphasized. Gravitational force can ameliorate the onset of respiratory
      colonization. The mechanism and clinical applicability of such observations need
      to be explored further.

PMID- 18829802
TI  - Retrospective evaluation of a computerized physician order entry adaptation to
      prevent prescribing errors in a pediatric emergency department.
AB  - OBJECTIVE: The goal was to determine the impact on medication prescribing errors
      of adding a pediatric medication list (quicklist) to a computerized physician
      order entry system in a pediatric emergency department. METHODS: The quicklist is
      a drug dosing support tool that targets the most common medications in our
      clinical setting. We performed a retrospective comparison of orders from 420
      randomly selected visits before and after quicklist introduction. Error rates
      were analyzed with respect to urgency level, physician training level, and
      patient age. The quicklist was examined for frequency of use and error rates.
      RESULTS: The 840 patient visits (420 before intervention and 420 after
      intervention) generated 724 medication orders, which contained 156 medication
      prescribing errors (21%). The groups did not differ with respect to urgency
      level, physician training level, or patient age. There were significant decreases
      in the rate of errors per 100 visits, from 24 to 13 errors per 100 visits, and in
      the rate of errors per 100 orders, from 31 to 14 errors per 100 orders. The
      decrease in the error rates did not vary according to urgency score, age group,
      or physician training level. The quicklist was used in 30% of the orders in the
      postintervention group. In this group, the error rate was 1.9 errors per 100
      orders when the quicklist was used, compared with 18.3 errors per 100 orders when
      the list was not used. Errors of wrong formulation, allergy, drug-drug
      interaction, and rule violations were eliminated. CONCLUSION: The introduction of
      the quicklist was followed by a significant reduction in medication prescribing
      errors. A list with dosing support for commonly used pediatric medications may
      help adapt computerized physician order entry systems designed for adults to
      serve pediatric populations more effectively.

PMID- 18829801
TI  - Do cortisol concentrations predict short-term outcomes in extremely low birth
      weight infants?
AB  - OBJECTIVE: Relative adrenal insufficiency in extremely low birth weight infants
      may contribute to significant morbidity and death. Our objective was to evaluate
      the relationship between cortisol concentrations and short-term outcomes.
      METHODS: Cortisol concentrations were obtained for 350 intubated, extremely low
      birth weight infants at postnatal age of 12 to 48 hours and at day 5 to 7, as
      part of a multicenter, randomized trial of hydrocortisone treatment for
      prophylaxis of relative adrenal insufficiency. Death and short-term morbidity
      were monitored prospectively. Cortisol levels at each time point were divided
      into quartiles. The incidence rates of outcomes were determined for each quartile
      and for infants with cortisol values of <10th percentile or >90th percentile.
      RESULTS. Median cortisol values were 16.0 microg/dL at baseline and 13.1
      microg/dL on day 5 to 7 in the placebo group. Outcomes did not differ in each
      quartile between treatment and placebo groups. Low cortisol values at baseline or
      day 5 to 7 were not associated with increased morbidity or mortality rates and
      were not predictive of open-label hydrocortisone use. In fact, vasopressor use
      was lower for infants with lower cortisol values at baseline. Severe
      intraventricular hemorrhage was more frequent in infants with cortisol levels in
      the upper quartile at baseline, and values of >90th percentile were significantly
      associated with higher rates of death, severe intraventricular hemorrhage,
      periventricular leukomalacia, gastrointestinal perforation, and severe
      retinopathy of prematurity. CONCLUSIONS: Low cortisol concentrations were not
      predictive of adverse short-term outcomes, but high cortisol concentrations were
      associated with severe intraventricular hemorrhage, and extremely elevated values
      were associated with morbidity and death. Low cortisol concentrations alone at
      these 2 time points did not identify the infants at highest risk for adverse
      outcomes. In contrast, high cortisol values were associated with increased
      morbidity and mortality rates.

PMID- 18829803
TI  - Reducing the risk of sudden infant death syndrome in child care and changing
      provider practices: lessons learned from a demonstration project.
AB  - OBJECTIVE: The goal was to evaluate, through an American Academy of Pediatrics
      demonstration project, the effectiveness of a curriculum and train-the-trainer
      model in changing child care providers' behaviors regarding safe infant sleep
      practices. METHODS: Participating licensed child care centers and family child
      care homes were assigned randomly to intervention and control groups. Observers
      performed an initial unannounced visit to each site, to watch infants being
      placed for sleep, to inventory sleep policies, and to administer questionnaires
      to center staff members. Trainers then used the American Academy of Pediatrics
      curriculum in educational sessions at intervention sites. Three months later,
      observers conducted a follow-up observation at each site, and staff members
      completed a questionnaire about logistic barriers encountered in implementation
      of safe sleep recommendations. RESULTS: A total of 264 programs and 1212
      providers completed the study; the care of 1993 infants was observed. Provider
      awareness of the American Academy of Pediatrics infant supine sleep position
      recommendation increased from 59.7% (both groups) to 64.8% (control) and 80.5%
      (intervention). Exclusive use of the supine position in programs increased from
      65.0% to 70.4% (control) and 87.8% (intervention). Observed supine placement
      increased from 51.0% to 57.1% (control) and 62.1% (intervention). CONCLUSIONS: A
      sudden infant death syndrome risk reduction curriculum using a train-the-trainer
      model is effective in improving the knowledge and practices of child care
      providers. Perceived parental objections, provider skepticism about the benefits
      of supine positioning, and lack of program policies and training opportunities
      are important barriers to implementation of safe sleep policies. Continued
      education of parents, expanded training efforts, and statewide regulations,
      mandates, and monitoring are critical to ongoing efforts to decrease further the
      risk of sudden infant death syndrome in child care.

PMID- 18829804
TI  - Preventing unintentional scald burns: moving beyond tap water.
AB  - OBJECTIVE: The goal was to examine in detail the mechanisms of significant scald
      burns among children <5 years of age, to discover insights into prevention.
      METHODS: Medical records for children <5 years of age who were admitted with
      scald burns between January 1, 2002, and December 31, 2004, were identified
      through the University of Chicago Burn Center database. Demographic data and
      details of the circumstances and mechanisms of injury were extracted from the
      medical records. RESULTS: Of 640 admissions to the University of Chicago Burn
      Center during the 3-year study period, 140 (22%) involved children <5 years of
      age with scald burns. Of the 137 available charts reviewed, 118 involved
      unintentional injuries. Of those unintentional injuries, 14 were tap water scalds
      and 104 were non-tap water scalds. Of the non-tap water scalds, 94 scalds (90.4%)
      were related to hot cooking or drinking liquids. Two unexpected patterns of
      injury were discovered. Nine children (8.7%) between the ages of 18 months and 4
      years were scalded after opening a microwave oven and removing the hot substance
      themselves. Seventeen children (16.3%) were scalded while an older child, 7 to 14
      years of age, was cooking or carrying the scalding substance or supervising the
      younger child. CONCLUSIONS: Current prevention strategies and messages do not
      adequately address the most common mechanisms of scald injury requiring
      hospitalization. Easy access to a microwave oven poses a significant scald risk
      to children as young as 18 months of age, who can open the door and remove the
      hot contents. An engineering fix for microwave ovens could help protect young
      children from this mechanism of scalding. Involvement of older children in a
      subset of scald injuries is a new finding that may have prevention implications.

PMID- 18829805
TI  - Influenza-associated pediatric mortality in the United States: increase of
      Staphylococcus aureus coinfection.
AB  - OBJECTIVE: Pediatric influenza-associated death became a nationally notifiable
      condition in the United States during 2004. We describe influenza-associated
      pediatric mortality from 2004 to 2007, including an increase of Staphylococcus
      aureus coinfections. METHODS: Influenza-associated pediatric death is defined as
      a death of a child who is younger than 18 years and has laboratory-confirmed
      influenza. State and local health departments report to the Centers for Disease
      Control and Prevention demographic, clinical, and laboratory data on influenza
      associated pediatric deaths. RESULTS: During the 2004-2007 influenza seasons, 166
      influenza-associated pediatric deaths were reported (n = 47, 46, and 73,
      respectively). Median age of the children was 5 years. Children often progressed
      rapidly to death; 45% died within 72 hours of onset, including 43% who died at
      home or in an emergency department. Of 90 children who were recommended for
      influenza vaccination, only 5 (6%) were fully vaccinated. Reports of bacterial
      coinfection increased substantially from 2004-2005 to 2006-2007 (6%, 15%, and
      34%, respectively). S aureus was isolated from a sterile site or endotracheal
      tube culture in 1 case in 2004-2005, 3 cases in 2005-2006, and 22 cases in 2006
      2007; 64% were methicillin-resistant S aureus. Children with S aureus coinfection
      were significantly older and more likely to have pneumonia and acute respiratory
      distress syndrome than those who were not coinfected. CONCLUSIONS: Influenza
      associated pediatric mortality is rare, but the proportion of S aureus
      coinfection identified increased fivefold over the past 3 seasons. Research is
      needed to identify risk factors for influenza coinfection with invasive bacteria
      and to determine the impact of influenza vaccination and antiviral agents in
      preventing pediatric mortality.

PMID- 18829806
TI  - Management of atopic dermatitis in the pediatric population.
AB  - Atopic dermatitis, one of the most common skin disorders in young children, has a
      prevalence of 10% to 20% in the first decade of life. It is a chronic illness
      that requires a multifaceted treatment strategy in the setting of limited
      therapeutic options. Balancing safety concerns with efficacious treatment is of
      particular importance in the pediatric population. Parents of patients with
      atopic dermatitis turn to their primary caregivers for guidance regarding this
      physically demanding and psychologically stressful condition. In addition to
      serving as a review of atopic dermatitis, this article delves into the state-of
      the-art therapeutic options and includes a detailed review of the differences
      between topical corticosteroids and topical calcineurin inhibitors. We also
      discuss new treatment strategies that are being used by atopic dermatitis
      specialists, such as comprehensive "education-as-intervention" models, wet wraps,
      bleach baths, and systemic immunomodulatory therapies.

PMID- 18829808
TI  - Sodium bicarbonate: basically useless therapy.
AB  - Common clinical practices often are unsupported by experimental evidence. One
      example is the administration of sodium bicarbonate to neonates. Despite a long
      history of widespread use, objective evidence that administration of sodium
      bicarbonate improves outcomes for patients in cardiopulmonary arrest or with
      metabolic acidosis is lacking. Indeed, there is evidence that this therapy is
      detrimental. This review examines the history of sodium bicarbonate use in
      neonatology and the evidence that refutes the clinical practice of administering
      sodium bicarbonate during cardiopulmonary resuscitation or to treat metabolic
      acidosis in the NICU.

PMID- 18829807
TI  - Systematic review of digital imaging screening strategies for retinopathy of
      prematurity.
AB  - BACKGROUND: Retinal imaging with remote interpretation could decrease the number
      of diagnostic eye examinations that premature infants need for the detection of
      retinopathy of prematurity and thus decrease the time demand on the relatively
      small pool of ophthalmologists who perform retinopathy of prematurity
      examinations. OBJECTIVE: Our goal was to review systematically the evidence
      regarding the reliability, validity, safety, costs, and benefits of retinal
      imaging to screen infants who are at risk for retinopathy of prematurity.
      METHODS: We searched Medline, the Cochrane library, CINAHL, and the
      bibliographies of all relevant articles. All English-language studies regardless
      of design with primary data about our study questions were included. We excluded
      (1) studies that only included subjects with retinopathy of prematurity, (2)
      hypothetical models other than cost-effectiveness studies, and (3) validity
      studies without sufficient data to determine prevalence, sensitivity, and
      specificity or that only evaluated subjects for 1 component of retinopathy of
      prematurity (eg, plus disease only). RESULTS: Studies of only 1 retinal imaging
      device (RetCam [Clarity Medical Systems, Inc, Pleasanton, CA]) met the inclusion
      criteria. There was a wide range in reported sensitivity, but specificity was
      high. There were several important limitations noted, including the eye as the
      unit of analysis instead of the individual or variations in the criteria for
      determining a true-positive or true-negative screening result. The risk of
      retinal hemorrhage resulting from imaging is low, and systemic effects (eg,
      bradycardia, hypertension, decreased oxygen saturation) are mild. No
      generalizable cost-effectiveness data were found. CONCLUSIONS: The evidence base
      is not sufficient to recommend that retinal imaging be routinely adopted by NICUs
      to identify infants who have serious retinopathy of prematurity.

PMID- 18829809
TI  - Pediatric private practice after Hurricane Katrina: proposal for recovery.
AB  - The health care system of the US Gulf Coast was severely damaged by Hurricane
      Katrina in August 2005. Physicians in the region have faced enormous financial
      and psychological challenges. Pediatricians have been particularly affected,
      because of the large number of children covered by Medicaid, with its associated
      low payments, and the failure of children and families to return to affected
      areas. Federal relief efforts to date have largely benefited nonprofit
      organizations, community health centers, and hospitals. Private physicians have
      received little to no governmental assistance, despite their vital role in the
      health care system. This article explores the many factors threatening the
      survival of pediatric private practice in the aftermath of Hurricane Katrina and
      offers some practical governmental solutions. The proposals outlined here aim to
      provide stability and recovery to health care in the region by enabling residents
      to obtain care from local preexisting providers on the Gulf Coast and ensuring
      that physicians are paid adequately for their services. These ideas have
      applicability beyond Hurricane Katrina and should encourage thought regarding
      health care delivery after future regional disasters.

PMID- 18829810
TI  - A National Agenda for America's Children and Adolescents in 2008: recommendations
      from the 15th Annual Public Policy Plenary Symposium, annual meeting of the
      Pediatric Academic Societies, May 3, 2008.

PMID- 18829811
TI  - Amplitude-integrated electroencephalography in the newborn: a valuable tool.

PMID- 18829812
TI  - The thorny nature of predictive validity studies on screening tests for
      developmental-behavioral problems.

PMID- 18829813
TI  - Recurrence of sudden infant death syndrome.

PMID- 18829814
TI  - New book about vaccine safety.

PMID- 18829815
TI  - Is there a "normal" range of serum cortisol concentration for preterm infants?

PMID- 18829816
TI  - Exposure to nontraditional pets at home and to animals in public settings: risks
      to children.
AB  - Exposure to animals can provide many benefits during the growth and development
      of children. However, there are potential risks associated with animal exposures,
      including exposure to nontraditional pets in the home and animals in public
      settings. Educational materials, regulations, and guidelines have been developed
      to minimize these risks. Pediatricians, veterinarians, and other health care
      professionals can provide advice on selection of appropriate pets as well as
      prevention of disease transmission from nontraditional pets and when children
      contact animals in public settings.

PMID- 18829817
TI  - Medical emergencies occurring at school.
AB  - Children and adults might experience medical emergency situations because of
      injuries, complications of chronic health conditions, or unexpected major
      illnesses that occur in schools. In February 2001, the American Academy of
      Pediatrics issued a policy statement titled "Guidelines for Emergency Medical
      Care in Schools" (available at:
      http://aappolicy.aappublications.org/cgi/content/full/pediatrics;107/2/435).
      Since the release of that statement, the spectrum of potential individual student
      emergencies has changed significantly. The increase in the number of children
      with special health care needs and chronic medical conditions attending schools
      and the challenges associated with ensuring that schools have access to on-site
      licensed health care professionals on an ongoing basis have added to increasing
      the risks of medical emergencies in schools. The goal of this statement is to
      increase pediatricians' awareness of schools' roles in preparing for individual
      student emergencies and to provide recommendations for primary care and school
      physicians on how to assist and support school personnel.

PMID- 18829818
TI  - Disaster planning for schools.
AB  - Community awareness of the school district's disaster plan will optimize a
      community's capacity to maintain the safety of its school-aged population in the
      event of a school-based or greater community crisis. This statement is intended
      to stimulate awareness of the disaster-preparedness process in schools as a part
      of a global, community-wide preparedness plan. Pediatricians, other health care
      professionals, first responders, public health officials, the media, school
      nurses, school staff, and parents all need to be unified in their efforts to
      support schools in the prevention of, preparedness for, response to, and recovery
      from a disaster.

PMID- 18829819
TI  - Mercury levels in newborns and infants after receipt of thimerosal-containing
      vaccines.

PMID- 18829820
TI  - Limitations in the agency for healthcare research and quality pediatric quality
      indicators result in flawed call for national benchmarks.

PMID- 18829821
TI  - An assessment of the new lipid screening guidelines.

PMID- 18829822
TI  - Vitamin D deficiency and insufficiency in children with osteopenia or
      osteoporosis.

PMID- 18829823
TI  - Head covering, sweating, and the risk of sudden infant death syndrome.

PMID- 18829824
TI  - Overweight in children and adolescents in relation to attention
      deficit/hyperactivity disorder.

PMID- 18829825
TI  - Maternally reported food allergies and other food-related health problems in
      infants: characteristics and associated factors.
AB  - OBJECTIVE: Our goal was to identify the frequency, demographics, and diagnostic
      characteristics associated with maternally reported food allergies and other food
      related health problems among infants aged < or = 1 year. METHODS: We analyzed
      data from the 2005-2007 Infant Feeding Practices Study II, a longitudinal survey
      of 2441 US mothers of healthy singletons from pregnancy through their infant's
      first year. Doctor diagnosis and symptoms-based criteria were used to identify a
      probable-food-allergic group from maternal reports of infant health problems with
      food. RESULTS: More than one fifth of the 2441 mothers reported that their infant
      had a food-related problem; 6% (n = 143) had a probable food allergy, and 15% (n
      = 359) had other food-related problems. Forty percent of the infants with a food
      related health problem were evaluated by a doctor. Gastrointestinal symptoms were
      more commonly reported in early infancy compared with skin-related symptoms,
      which were reported in later infancy, and 27% received medical treatment for the
      symptoms. Characteristics associated with increased incidence of probable food
      allergy included family histories of food allergy and type 1 diabetes,
      gestational diabetes, living in rural or urban areas, being black, and being
      male. Among all infants with a food-related health problem, the majority
      experienced their first problem by 6 months of age. Foods recognized to be major
      allergens were most commonly reported as the source of an allergy. CONCLUSIONS:
      Food-related problems occurred at a high frequency in the first year of life. A
      better understanding of the demographics, family history, disease manifestations,
      and diagnoses may provide insight into public health efforts to minimize or
      prevent food allergies in infancy and to help differentiate food-allergic
      problems from nonallergic food problems in this age group.

PMID- 18829826
TI  - Infant sleeping arrangements and practices during the first year of life.
AB  - OBJECTIVES: Our goal was to examine the sleeping arrangements for infants from
      birth to 1 year of age and to assess the association between such arrangements
      and maternal characteristics. METHODS: Responses to the 3-, 6-, 9-, and 12-month
      questionnaires from the Infant Feeding Practices Study II were analyzed to assess
      sleep arrangements, including bed sharing, the latter defined as mother ever (in
      a given time frame) slept with the infant on the same sleeping surface for
      nighttime sleep. Women were also asked about the reasons for bed sharing or not
      bed sharing. RESULTS: Approximately 2300 women responded at 3 months, and 1800 at
      12 months. At 3 months, 85% of the infants slept in the same room as their
      mother, and at 12 months that rate was 29%. At 3 months, 26% of the mothers did
      not use the recommended supine position for their infant's nighttime sleep. The
      rate of noncompliance increased to 29% by 6 months and 36% by 12 months. The bed
      sharing rates were 42% at 2 weeks, 34% at 3 months, and 27% at 12 months.
      Approximately two thirds of those who bed shared with their infant also shared
      the bed with their husband or partner, and 5% to 15% shared it with other
      children. The major reasons for bed sharing were to calm a fussy infant,
      facilitate breastfeeding, and help the infant and/or mother sleep better. The
      major reasons for not lying down with the infant were safety concerns. Non
      Hispanic black mothers were more likely than non-Hispanic white mothers to use
      nonsupine infant sleep positions and to bed share. CONCLUSIONS: More than one
      third of the women in this cohort were noncompliant with safe-sleeping guidelines
      when their infant was 3 months old. Health care providers need to advise parents
      of current recommendations and discuss the risks and benefits of their choices
      for infant sleeping practices.

PMID- 18829827
TI  - Infant feeding and care practices in the United States: results from the Infant
      Feeding Practices Study II.

PMID- 18829828
TI  - Infant Feeding Practices Study II: study methods.
AB  - OBJECTIVE: Our goal is to describe the methods used in the Infant Feeding
      Practices Study II (IFPS II), a study of infant feeding and care practices
      throughout the first year of life. Survey topics included breastfeeding, formula
      and complementary feeding, infant health, breast-pump use, food allergies,
      sleeping arrangements, mother's employment, and child care arrangements. In
      addition, mothers' dietary intake was measured prenatally and postnatally.
      PARTICIPANTS AND METHODS: The IFPS II sample was drawn from a nationally
      distributed consumer opinion panel of 500,000 households. All questionnaires were
      administered by mail, 1 prenatally and 10 postpartum. Qualifying criteria were
      used to achieve the sample goals of mothers of healthy term and late preterm
      singleton infants. In addition to the questionnaires about the infants, women
      were sent a diet-assessment questionnaire prenatally and at approximately 4
      months after delivery; this questionnaire was also sent to members of a
      comparison group who were neither pregnant nor postpartum. RESULTS: A sample of
      4902 pregnant women began the study, and approximately 2000 continued through
      their infant's first year. Response rates ranged from 63% to 87% for the
      different questionnaires. Compared with adult mothers of singletons from the
      nationally representative sample of the National Survey of Family Growth, IFPS II
      participants had a higher mean education level; were older; were more likely to
      be middle income, white, and employed; were less likely to smoke; and had fewer
      other children. Compared with women who participated in the National Immunization
      Survey who gave birth in 2004, IFPS II mothers were more likely to breastfeed and
      to breastfeed longer. CONCLUSIONS: The IFPS II provides a valuable database
      because of its large sample size, the frequency of its questionnaires, and its
      wide coverage of issues salient to infant feeding.

PMID- 18829829
TI  - Infant feeding and feeding transitions during the first year of life.
AB  - OBJECTIVE: Infancy is a time of rapid transition from a diet of virtually nothing
      but milk (either breast milk or infant formula) to a varied diet from nearly all
      food groups being consumed on a daily basis by most infants. Despite various
      recommendations about infant feeding, little is known about actual patterns of
      feeding among US infants. This article documents transitions in infant feeding
      patterns across the first year of life and determinants of key aspects of infant
      feeding. METHODS: Using data from the Infant Feeding Practices Study II, we
      analyzed responses to a 7-day food-recall chart that was administered every
      month. The sample size declined from 2907 at birth to 1782 at 12 months of age.
      RESULTS: Although 83% of survey respondents initiated breastfeeding, the
      percentage who breastfed declined rapidly to 50% at 6 months and to 24% at 12
      months. Many of the women who breastfed also fed their infants formula; 52%
      reported that their infants received formula while in the hospital. At 4 months,
      40% of the infants had consumed infant cereal, 17% had consumed fruit or
      vegetable products, and <1% had consumed meat. Compared with infants who were not
      fed solid foods at 4 months, those who were fed solid foods were more likely to
      have discontinued breastfeeding at 6 months (70% vs 34%) and to have been fed
      fatty or sugary foods at 12 months (75% vs 62%). CONCLUSIONS: Supplementing
      breast milk with infant formula while infants were still in the hospital was very
      common. Despite recommendations that complementary foods not be introduced to
      infants aged 4 months or younger, almost half of the infants in this study had
      consumed solid foods by the age of 4 months. This early introduction of
      complementary foods was associated with unhealthful subsequent feeding behaviors.

PMID- 18829830
TI  - Effect of maternity-care practices on breastfeeding.
AB  - OBJECTIVE: Our goal was to assess the impact of "Baby-Friendly" hospital
      practices and other maternity-care practices experienced by mothers on
      breastfeeding duration. METHODS: This analysis of the Infant Feeding Practices
      Study II focused on mothers who initiated breastfeeding and intended prenatally
      to breastfeed for >2 months, with complete data on all variables (n = 1907).
      Predictor variables included indicators of 6 "Baby-Friendly" practices
      (breastfeeding initiation within 1 hour of birth, giving only breast milk,
      rooming in, breastfeeding on demand, no pacifiers, fostering breastfeeding
      support groups) along with several other maternity-care practices. The main
      outcome measure was breastfeeding termination before 6 weeks. RESULTS: Only 8.1%
      of the mothers experienced all 6 "Baby-Friendly" practices. The practices most
      consistently associated with breastfeeding beyond 6 weeks were initiation within
      1 hour of birth, giving only breast milk, and not using pacifiers. Bringing the
      infant to the room for feeding at night if not rooming in and not giving pain
      medications to the mother during delivery were also protective against early
      breastfeeding termination. Compared with the mothers who experienced all 6 "Baby
      Friendly" practices, mothers who experienced none were approximately 13 times
      more likely to stop breastfeeding early. Additional practices decreased the risk
      for early termination. CONCLUSIONS: Increased "Baby-Friendly" hospital practices,
      along with several other maternity-care practices, improve the chances of
      breastfeeding beyond 6 weeks. The need to work with hospitals to implement these
      practices continues to exist, as illustrated by the small proportion of mothers
      who reported experiencing all 6 of the "Baby-Friendly" hospital practices
      measured in this study.

PMID- 18829831
TI  - Characteristics of breastfeeding practices among US mothers.
AB  - OBJECTIVES: Although much has been published about breastfeeding rates, little is
      known about how breastfeeding is practiced in the United States. We describe the
      distributions and characteristics of practices related to common advice about
      breastfeeding during the infant's first year of life. PARTICIPANTS AND METHODS:
      Participants in the 2005-2007 Infant Feeding Practices Study II received monthly
      questionnaires during their infants' first year of life. Among breastfeeding
      respondents, we investigated patterns and trends in types of breastfeeding
      (supplementing with formula or not, and at the breast or not) and maternal report
      of infant feeding behaviors corresponding to common breastfeeding advice on
      frequency, duration, and intervals of feedings. RESULTS: More than half of the
      breastfeeding mothers fed their infants nothing other than breast milk until 4
      months of age. Formula supplementation declined from 42% at 1 month to 15% at 1
      year; adding other foods/liquids increasingly surpassed supplementing with
      formula beginning at 5 months of age. Six percent of the mothers reported that
      the only breast milk the infant was fed was expressed, rather than at the breast.
      Frequency of breast milk feedings per day declined from 8 at 1 month to 3.5 at 1
      year. Reported feeding durations of <20 minutes increased from 46% at 1 month to
      88% at 1 year. Feeding from both breasts per feeding decreased 15% over the
      infant's first year (from 69% to 59%). Longest interfeeding intervals more than
      doubled over the year. CONCLUSIONS: Exclusive breastfeeding was common up to 4
      but not to 6 months of age. Breastfeeding with only expressed milk was rare.
      Considerable variation existed in maternal report of practices that correspond to
      common breastfeeding advice. More research is needed to better understand how
      these variations relate to breastfeeding outcomes and the role of common
      breastfeeding advice in infant feeding decisions.

PMID- 18829832
TI  - Success of strategies for combining employment and breastfeeding.
AB  - OBJECTIVE: Return to work is associated with diminished breastfeeding intensity
      and duration. Although more mothers breastfeed after returning to work now than
      earlier, research has not documented the strategies that mothers use for
      combining paid work and breastfeeding or their effect on breastfeeding outcomes.
      This study examined which strategies are associated with smaller decrements in
      breastfeeding intensity and longer durations. PARTICIPANTS AND METHODS: We
      analyzed 810 mothers from the Infant Feeding Practices Study II who worked and
      breastfed. We used regression and censored regression models to analyze 4
      strategies that mothers used to combine these 2 activities: (1) feed directly
      from the breast only; (2) both pump and feed directly; (3) pump only; and (4)
      neither pump nor breastfeed during the work day. Outcomes were the difference in
      percentage of milk feeds that were breast milk between the month before and after
      return to work and duration of breastfeeding after return to work. RESULTS: Forty
      three percent of mothers pumped milk at work only; 32% fed the infant directly
      from the breast only. These 2 strategies, along with pumping and feeding
      directly, were statistically similar and superior to neither pumping nor
      breastfeeding during the work day for the outcome of change in breastfeeding
      intensity. For the outcome of breastfeeding duration, the 2 strategies that
      included directly feeding from the breast were associated with longer duration
      than pumping only, whereas the strategy of neither pumping nor breastfeeding
      during the work day was associated with the shortest duration. CONCLUSIONS:
      Feeding the infant from the breast during the work day is the most effective
      strategy for combining breastfeeding and work. Ways to enable direct feeding
      include on-site child care, telecommuting, keeping the infant at work, allowing
      the mother to leave work to go to the infant, and having the infant brought to
      the work site. Establishing ways for mothers to feed from the breast after return
      to work is important to meet US breastfeeding goals.

PMID- 18829833
TI  - Prevalence of breast milk expression and associated factors.
AB  - OBJECTIVES: Our goal was to describe the prevalence of any, occasional, and
      regular breast milk expression, mothers' reasons for expressing their milk, and
      sociodemographic factors associated with breast milk expression. PARTICIPANTS AND
      METHODS: Breastfeeding mothers participating in the 2005-2007 Infant Feeding
      Practices Study II formed the cohort for these analyses, which were conducted
      among those with infants in 3 age groups: 1.5 to 4.5 months (n = 1564); >4.5 to
      6.5 months (n = 1128); and >6.5 to 9.5 months (n = 914). For the analyses we used
      frequency and stepwise multiple logistic regression procedures. RESULTS: Eighty
      five percent of breastfeeding mothers of infants in the youngest age group had
      successfully expressed milk at some time since their infant was born. When asked
      only about the previous 2-week period, 68% of the breastfeeding mothers of
      infants in this youngest age group had expressed milk, with 43% having done so
      occasionally and 25% on a regular schedule. Approximately one quarter of
      breastfeeding mothers of infants in the 2 older infant age groups also expressed
      milk on a regular schedule. The percentage of mothers expressing milk decreased
      with increasing infant age. Mothers expressed milk for various reasons. The most
      frequently cited reason was to get breast milk for someone else to feed their
      infant. In all 3 age groups, reporting any breast milk expression, compared with
      none, was positively associated with maternal employment, higher income, lack of
      previous breastfeeding experience, and living in the Midwest versus the West. In
      all 3 age groups, expressing milk on a regular schedule, compared with
      occasionally, was positively associated with maternal employment and the use of
      an electric versus manual breast pump. CONCLUSIONS: Breast milk expression is a
      very common practice. It is associated most strongly with maternal employment, a
      recognized barrier to breastfeeding.

PMID- 18829834
TI  - Why mothers stop breastfeeding: mothers' self-reported reasons for stopping
      during the first year.
AB  - OBJECTIVES: Our goal was to determine why women stop breastfeeding at various
      times during their infant's first year. METHODS: We analyzed self-reported data
      from 1323 mothers who participated in the Infant Feeding Practice Study II. Mail
      questionnaires were sent to mothers approximately 2, 3, 4, 5, 6, 7, 9, 10 1/2,
      and 12 months after their child's birth, in which they were asked to rate the
      importance of 32 reasons for their decision to stop breastfeeding. We applied
      exploratory factorial analysis to extract meaningful constructs of mothers'
      responses to the 32 reasons. We then compared the percentages of mothers who
      indicated that each reason was important in their decision to stop breastfeeding
      among various weaning ages and used multiple logistic regression models to
      examine sociodemographic differences in the most frequently cited reasons for
      stopping breastfeeding. RESULTS: The perception that their infant was not
      satisfied by breast milk alone was cited consistently as 1 of the top 3 reasons
      in the mothers' decision to stop breastfeeding regardless of weaning age (43.5%
      55.6%) and was even more frequent among Hispanic mothers and mothers with annual
      household incomes of <350% of the federal poverty level. Mothers' concerns about
      lactation and nutrition issues were the most frequently cited reasons for
      stopping breastfeeding during the first 2 months. Starting from the third month,
      self-weaning reasons were increasingly cited as important, with the statements
      "My baby began to bite" (31.7%), "My baby lost interest in nursing or began to
      wean himself or herself" (47.3%), and "Breast milk alone did not satisfy my baby"
      (43.5%) cited as the top 3 reasons at > or = 9 months of age. CONCLUSIONS: Our
      findings about the major reasons why mothers stop breastfeeding at various times
      during their child's first year should be useful to health professionals when
      attempting to help mothers overcome breastfeeding barriers and to health
      officials attempting to devise targeted breastfeeding interventions on those
      issues prominent for each infant age.

PMID- 18829835
TI  - Association of breastfeeding intensity and bottle-emptying behaviors at early
      infancy with infants' risk for excess weight at late infancy.
AB  - OBJECTIVE: Our goal was to test the hypothesis that infants who were breastfed
      more intensively during early infancy (< or = 6 months) will be less likely to
      have excess weight during late infancy (> 6 months) and to examine the
      independent impact of infant-initiated bottle emptying and mothers' encouragement
      of bottle emptying on infants' risk for excess weight. METHOD: The sample
      consisted of 1896 mothers who participated in postpartum surveys of the Infant
      Feeding Practice Study II and who provided at least 1 weight measurement of their
      infants during the second half of infancy. We used multiple logistic regression
      models to assess the association between infants' risks for excess weight during
      the second half of infancy and 3 self-reported feeding practices during the first
      half of infancy after adjusting for a series of sociodemographic characteristics.
      The early feeding practices examined included the percentage of all milk feedings
      in which infants consumed breast milk (breastfeeding intensity), the frequency of
      bottle feedings in which infants initiated bottle emptying, and the frequency of
      bottle feedings in which mothers encouraged bottle emptying. RESULTS: Infants fed
      with low (< 20% of milk feeds being breast milk) and medium (20%-80%)
      breastfeeding intensity in the first half of infancy were at least 2 times more
      likely to have excess weight during the second half of infancy than those
      breastfed at high intensity (> 80%). Infants who often emptied bottles in early
      infancy were 69% more likely than those who rarely emptied bottles to have excess
      weight during late infancy. However, mothers' encouragement of bottle emptying
      was negatively associated with their infants' risk for excess weight during the
      second half of infancy. CONCLUSIONS: Infants' risk for excess weight during late
      infancy was negatively associated with breastfeeding intensity but positively
      associated with infant-initiated bottle emptying during early infancy. These
      findings not only provide evidence for the potential risk of not breastfeeding or
      breastfeeding at a low intensity in development of childhood obesity, but they
      also suggest that infant-initiated bottle emptying may be an independent risk
      factor as well.

PMID- 18829836
TI  - Infant formula-handling education and safety.
AB  - OBJECTIVES: Our goal was to assess the extent to which mothers learn about proper
      handling of infant formula from health professionals and package labels; mothers'
      beliefs about the likelihood of germs being in infant formula and the importance
      of following safe-use directions; whether they take measures while handling
      infant formula to prevent foodborne illnesses and injury to their infants; and
      maternal characteristics associated with unsafe infant formula-handling
      practices. PARTICIPANTS AND METHODS: The study cohort consisted of mothers
      participating in the 2005-2007 Infant Feeding Practices Study II who fed their
      infant formula. We conducted frequency and multiple logistic regression analyses.
      Sample sizes for the analyses ranged from 860 to 1533. RESULTS: The majority of
      formula-feeding mothers did not receive instruction on formula preparation (77%)
      or storage (73%) from a health professional. Thirty percent did not read some of
      the safe-use directions on the formula package label; an approximately equal
      percentage (38%) thought that both powdered (which is not sterile) and ready-to
      feed (which is sterile) formula were unlikely to contain germs; and 85% believed
      that following safe-storage directions was very important. Among the mothers of
      the youngest infants analyzed, 55% did not always wash their hands with soap
      before preparing infant formula, 32% did not adequately wash bottle nipples
      between uses, 35% heated formula bottles in a microwave oven, and 6% did not
      always discard formula left standing for >2 hours. The prevalence of these unsafe
      practices was similar among mothers of older infants. No consistent pattern of
      maternal characteristics was associated with unsafe practices. CONCLUSIONS: Many
      mothers do not follow safe practices when preparing infant formula. Additional
      research is needed to understand why more mothers do not follow safe formula
      handling recommendations.

PMID- 18829837
TI  - Selected complementary feeding practices and their association with maternal
      education.
AB  - OBJECTIVE: As infants transition from a milk-based diet to one that includes most
      food groups, the timing of the transition, how infants are fed, and the quality
      of their diet can have important health implications. Our objective is to
      describe these factors for US infants. METHODS: We analyzed data from the Infant
      Feeding Practices Study II. Sample sizes varied for relevant questions from
      approximately 1600 to approximately 2400. We analyzed the prevalence of 14
      feeding practices and their association with the mothers' education and also
      examined participants' use of commercial baby foods. RESULTS: Approximately 21%
      of the mothers introduced solid foods before 4 months; 7% introduced solids after
      6 months. Twenty-nine percent of the mothers introduced > 3 new foods per week to
      infants aged 5 to 10 months. Approximately 20% of the mothers fed juice before 6
      months, fed cow's milk before 12 months, and fed infants < 5 times per day after
      5 months. Fourteen percent of the mothers chewed food for their infant.
      Approximately 15% of the mothers fed < 1 serving daily of either a fruit or
      vegetable to infants aged > or = 9 months, half added salt to their infant's
      food, and more than one third who added salt used noniodized salt. Approximately
      20% fed reduced-fat cow's milk at 1 year. Almost half of the 10-month-old infants
      had eaten restaurant food in a restaurant in the previous week, 22% had eaten
      carry-out food, and 28% had eaten either type of restaurant food > or = 2 times.
      The prevalence of 8 of the 14 unhealthful infant feeding practices we examined
      was inversely associated with maternal education. CONCLUSIONS: Nutrition and
      feeding guidance should be especially targeted to mothers with a high school
      education or less.

PMID- 18829838
TI  - Sources of supplemental iron among breastfed infants during the first year of
      life.
AB  - OBJECTIVES: Primary prevention of iron deficiency requires adequate iron intake.
      Although recommendations exist to promote adequate intake of iron among infants
      through iron-rich foods and iron supplements, few studies have examined adherence
      to these recommendations. Our objectives were to describe the consumption of iron
      rich foods, oral iron supplements, and iron-fortified formula among US infants
      and to assess adherence to iron-intake recommendations. METHODS: We analyzed data
      from the Infant Feeding Practices Study II, a longitudinal study of mothers and
      infants followed from late pregnancy through the first year of their infant's
      life. Mothers completed near-monthly questionnaires that assessed how frequently
      they fed their infants breast milk, formula, infant cereals, and meats in the
      previous 7 days and whether their infants were given an oral iron supplement > or
      = 3 times per week during the previous 2 weeks. We examined use of iron-fortified
      formula among infants who consumed formula; intake of cereal, meat, oral iron
      supplements, and formula among infants consuming any breast milk; and whether 6
      month-old breastfed and mixed-fed (breast milk and formula) infants consumed
      sources of supplemental iron with recommended frequency. RESULTS: At 6 months of
      age, 18% of the term breastfed and mixed-fed infants had not received infant
      cereal or meat in the previous 7 days, and 15% had not received infant cereal,
      meat, regular iron supplements, or formula; among solely breastfed infants, 23%
      had not received infant cereal, meat, or regular iron supplements. Fifty-eight
      percent of the mixed-fed infants and 70% of the solely breastfed infants received
      < 2 daily servings of infant cereal, meat, or formula combined and did not
      receive oral iron supplements > or = 3 times per week. Among preterm breastfed
      and mixed-fed infants, none received oral iron supplements > or = 3 times per
      week before 3 months of age, 2% received them at 3 months, and 13% received them
      at 10.5 months. CONCLUSIONS: Our findings indicate that recommendations regarding
      iron intake among breastfed infants are not being followed by a substantial
      proportion of mothers.

PMID- 18829839
TI  - The drug that launched a thousand sleds.

PMID- 18829840
TI  - ASPET celebrates its centennial anniversary. 1981-1990.

PMID- 18829841
TI  - From bioinformatics to bioassays: gleaning insights into protein structure
      function from disease-associated nsSNPs.

PMID- 18829843
TI  - Targeting cancer stem cells with phytochemicals.
AB  - Cancer, second only to heart disease, is the leading cause of death in the US.
      Although progress has been made in the early detection of cancer and in
      improvements of cancer therapies, the ability to provide long-term survival has
      been limited. Increasing evidence suggests that a minute, biologically unique
      population of cancer stem cells (SCs) exists in most neoplasms and may be
      responsible for tumor initiation, progression, metastasis, and relapse.
      Characterization of cancer SCs has led to the identification of key cellular
      activities that may make cancer SCs vulnerable to therapeutic interventions that
      target drug-effluxing capabilities, stem cell pathways, anti-apoptotic
      mechanisms, and induction of differentiation. Phytochemicals, compounds made from
      fruits, vegetables, and grains, possess anti-cancer properties and represent a
      promising therapeutic approach for the prevention and treatment of many cancers.
      This review summarizes the evidence for the cancer SC hypothesis and discusses
      the potential mechanisms by which phytochemicals might target cancer SCs.

PMID- 18829842
TI  - G protein-coupled receptors go extracellular: RhoA integrates the integrins.
AB  - The identification of downstream effectors of G protein-coupled receptors (GPCRs)
      is critical for understanding the interactions between signaling cascades and for
      developing new pharmacological approaches for controlling GPCR-mediated
      responses. RhoA is a small G protein that serves as a proximal downstream
      effector of numerous GPCRs and regulates a variety of basic cell functions,
      including migration, survival, and proliferation. Intriguingly, GPCR ligands such
      as thrombin, sphingosine-1-phosphate, and lysophosphatidic acid, which signal
      through G(12/13) and activate RhoA, have recently been shown to induce the
      expression of the extracellular matrix protein Cyr61 (i.e., CCN1). Cyr61 is
      secreted and interacts with cell surface integrins to activate kinase and
      transcriptional cascades that are also known to contribute to cell migration,
      survival, and proliferation. The GPCR/RhoA/Cyr61/integrin pathway defines a novel
      convergence mechanism for integrating GPCR-and integrin-dependent signaling
      cascades that may contribute to sustained and pathophysiological responses to
      GPCR activation.

PMID- 18829844
TI  - What can population calcium imaging tell us about neural circuits?
AB  - Calcium imaging of bulk-loaded fluorescent indicators can be used to record the
      spiking activity of hundreds of neurons. Recent advances promise imaging
      technologies that are faster, more efficient, and applicable to awake animals,
      thereby moving imaging capabilities closer to the traditional strengths of multi
      electrode arrays. This article reviews these technical achievements and discusses
      how they can help us achieve the goal of understanding neural circuits.

PMID- 18829845
TI  - Toward optimal target placement for neural prosthetic devices.
AB  - Neural prosthetic systems have been designed to estimate continuous reach
      trajectories (motor prostheses) and to predict discrete reach targets
      (communication prostheses). In the latter case, reach targets are typically
      decoded from neural spiking activity during an instructed delay period before the
      reach begins. Such systems use targets placed in radially symmetric geometries
      independent of the tuning properties of the neurons available. Here we seek to
      automate the target placement process and increase decode accuracy in
      communication prostheses by selecting target locations based on the neural
      population at hand. Motor prostheses that incorporate intended target information
      could also benefit from this consideration. We present an optimal target
      placement algorithm that approximately maximizes decode accuracy with respect to
      target locations. In simulated neural spiking data fit from two monkeys, the
      optimal target placement algorithm yielded statistically significant improvements
      up to 8 and 9% for two and sixteen targets, respectively. For four and eight
      targets, gains were more modest, as the target layouts found by the algorithm
      closely resembled the canonical layouts. We trained a monkey in this paradigm and
      tested the algorithm with experimental neural data to confirm some of the results
      found in simulation. In all, the algorithm can serve not only to create new
      target layouts that outperform canonical layouts, but it can also confirm or help
      select among multiple canonical layouts. The optimal target placement algorithm
      developed here is the first algorithm of its kind, and it should both improve
      decode accuracy and help automate target placement for neural prostheses.

PMID- 18829846
TI  - Contributions of central and peripheral TRPV1 receptors to mechanically evoked
      and spontaneous firing of spinal neurons in inflamed rats.
AB  - TRPV1 receptors are activated and/or modulated by noxious heat, capsaicin,
      protons and other endogenous agents released following tissue injury. There is a
      growing appreciation that this molecular integrator may also have a role in
      mechanosensation. To further understand this role, we investigated the systemic
      and site-specific effects of a selective TRPV1 receptor antagonist, A-889425, on
      low-intensity mechanical stimulation in inflamed rats. Systemic administration of
      A-889425 (30 and 100 micromol/kg po) reduced mechanical allodynia in complete
      Freund's adjuvant (CFA)-inflamed rats. Systemic A-889425 (3 and 10 micromol/kg
      iv) also decreased the responses of spinal wide dynamic range (WDR) neurons to
      low-intensity mechanical stimulation in CFA-inflamed but not uninjured rats. This
      effect of A-889425 was likely mediated via multiple sites since local injection
      of A-889425 into the spinal cord (1-3 nmol), ipsilateral hindpaw (200 nmol), and
      cerebral ventricles (30-300 nmol) all attenuated WDR responses to low-intensity
      mechanical stimulation. In addition to an effect on mechanotransmission, systemic
      administration of A-889425 reduced the spontaneous firing of WDR neurons in
      inflamed but not uninjured rats. Spontaneous firing is elevated after injury and
      may reflect ongoing pain in the animal. Local injection experiments indicated
      that this effect of A-889425 on spontaneous firing was mainly mediated via TRPV1
      receptors in the spinal cord. Thus the current data demonstrate that TRPV1
      receptors have an enhanced role after an inflammatory injury, impacting both low
      intensity mechanotransmission and possibly spontaneous pain. Furthermore this
      study delineates the differential contribution of central and peripheral TRPV1
      receptors to affect spontaneous or mechanically evoked firing of WDR neurons.

PMID- 18829847
TI  - Asymmetric operation of the locomotor central pattern generator in the neonatal
      mouse spinal cord.
AB  - The rhythmic voltage oscillations in motor neurons (MNs) during locomotor
      movements reflect the operation of the pre-MN central pattern generator (CPG)
      network. Recordings from MNs can thus be used as a method to deduct the
      organization of CPGs. Here, we use continuous conductance measurements and
      decomposition methods to quantitatively assess the weighting and phase tuning of
      synaptic inputs to different flexor and extensor MNs during locomotor-like
      activity in the isolated neonatal mice lumbar spinal cord preparation. Whole cell
      recordings were obtained from 22 flexor and 18 extensor MNs in rostral and caudal
      lumbar segments. In all flexor and the large majority of extensor MNs the
      extracted excitatory and inhibitory synaptic conductances alternate but with a
      predominance of inhibitory conductances, most pronounced in extensors. These
      conductance changes are consistent with a "push-pull" operation of locomotor CPG.
      The extracted excitatory and inhibitory synaptic conductances varied between 2
      and 56% of the mean total conductance. Analysis of the phase tuning of the
      extracted synaptic conductances in flexor and extensor MNs in the rostral lumbar
      cord showed that the flexor-phase-related synaptic conductance changes have
      sharper locomotor-phase tuning than the extensor-phase-related conductances,
      suggesting a modular organization of premotor CPG networks consisting of
      reciprocally coupled, but differently composed, flexor and extensor CPG networks.
      There was a clear difference between phase tuning in rostral and caudal MNs,
      suggesting a distinct operation of CPG networks in different lumbar segments. The
      highly asymmetric features were preserved throughout all ranges of locomotor
      frequencies investigated and with different combinations of locomotor-inducing
      drugs. The asymmetric nature of CPG operation and phase tuning of the conductance
      profiles provide important clues to the organization of the rodent locomotor CPG
      and are compatible with a multilayered and distributed structure of the network.

PMID- 18829848
TI  - Pyramidal neurons switch from integrators in vitro to resonators under in vivo
      like conditions.
AB  - During wakefulness, pyramidal neurons in the intact brain are bombarded by
      synaptic input that causes tonic depolarization, increased membrane conductance
      (i.e., shunting), and noisy fluctuations in membrane potential; by comparison,
      pyramidal neurons in acute slices typically experience little background input.
      Such differences in operating conditions can compromise extrapolation of in vitro
      data to explain neuronal operation in vivo. For instance, pyramidal neurons have
      been identified as integrators (i.e., class 1 neurons according to Hodgkin's
      classification of intrinsic excitability) based on in vitro experiments but that
      classification is inconsistent with the ability of hippocampal pyramidal neurons
      to oscillate/resonate at theta frequency since intrinsic oscillatory behavior is
      limited to class 2 neurons. Using long depolarizing stimuli and dynamic clamp to
      reproduce in vivo-like conditions in slice experiments, we show that CA1
      hippocampal pyramidal cells switch from integrators to resonators, i.e., from
      class 1 to class 2 excitability. The switch is explained by increased outward
      current contributed by the M-type potassium current I(M), which shifts the
      balance of inward and outward currents active at perithreshold potentials and
      thereby converts the spike-initiating mechanism as predicted by dynamical
      analysis of our computational model. Perithreshold activation of I(M) is enhanced
      by the depolarizing shift in spike threshold caused by shunting and/or sodium
      channel inactivation secondary to tonic depolarization. Our conclusions were
      validated by multiple comparisons between simulation and experimental data. Thus
      even so-called "intrinsic" properties may differ qualitatively between in vitro
      and in vivo conditions.

PMID- 18829849
TI  - Evidence for increased activation of persistent inward currents in individuals
      with chronic hemiparetic stroke.
AB  - Despite the prevalence of hyperactive stretch reflexes in the paretic limbs of
      individuals with chronic hemiparetic stroke, the fundamental pathophysiological
      mechanisms responsible for their expression remain poorly understood. This study
      tests whether the manifestation of hyperactive stretch reflexes following stroke
      is related to the development of persistent inward currents (PICs) leading to
      hyperexcitability of motoneurons innervating the paretic limbs. Because
      repetitive volleys of 1a afferent feedback can elicit PICs, this investigation
      assessed motoneuronal excitability by evoking the tonic vibration reflex (TVR) of
      the biceps muscle in 10 awake individuals with chronic hemiparetic stroke and
      measuring the joint torque and electromyographic (EMG) responses of the upper
      limbs. Elbow joint torque and the EMG activity of biceps, brachioradialis, and
      the long and lateral heads of triceps brachii were recorded during 8 s of 112-Hz
      biceps vibration (evoking the TVR) and for 5 s after cessation of stimulation.
      Repeated-measures ANOVA tests revealed significantly (P <or= 0.05) greater
      increases in elbow flexion torque and EMG activity in the paretic as compared
      with the nonparetic limbs, both during and up to 5 s following biceps vibration.
      The finding of these augmentations exclusively in the paretic limb suggests that
      contralesional motoneurons may become hyperexcitable and readily invoke PICs
      following stroke. An enhanced tendency to evoke PICs may be due to an increased
      subthreshold depolarization of motoneurons, an increased monoaminergic input from
      the brain stem, or both.

PMID- 18829850
TI  - Development of theta rhythmicity in entorhinal stellate cells of the juvenile
      rat.
AB  - Mature stellate cells of the rat medial entorhinal cortex (EC), layer II, exhibit
      subthreshold membrane potential oscillations (MPOs) at theta frequencies (4-12
      Hz) in vitro. We find that MPOs appear between postnatal days 14 (P14) and 18
      (P18) but show little further change by day 28+ (P28-P32). To identify the
      factors responsible, we examined the electrical responses of developing stellate
      cells, paying attention to two currents thought necessary for mature oscillation:
      the h current I(h), which provides the slow rectification required for resonance;
      and a persistent sodium current I(NaP), which provides amplification of
      resonance. Responses to injected current revealed that P14 cells were often
      nonresonant with a relatively high resistance. Densities of I(h) and I(NaP) both
      rose by about 50% from P14 to P18. However, I(h) levels fell to intermediate
      values by P28+. Given the nonrobust trend in I(h) expression and a previously
      demonstrated potency of even low levels of I(h) to sustain oscillation, we
      propose that resonance and MPOs are limited at P14 more by low levels of I(NaP)
      than of I(h). The relative importance of I(NaP) for the development of MPOs is
      supported by simulations of a conductance-based model, which also suggest that
      general shunt conductance may influence the precise age when MPOs appear. In
      addition to our physiological study, we analyzed spine densities at P14, P18, and
      P28+ and found a vigorous synaptogenesis across the whole period. Our data
      predict that functions that rely on theta rhythmicity in the hippocampal network
      are limited until at least P18.

PMID- 18829851
TI  - Evidence for joint encoding of motion and disparity in human visual perception.
AB  - Electrophysiological recordings have established that motion and disparity
      signals are jointly encoded by subpopulations of neurons in visual cortex.
      However, the question of whether these neurons play a perceptual role has proven
      challenging and remains open. To answer this question we combined two powerful
      psychophysical techniques: perceptual adaptation and reverse correlation. Our
      results provide a detailed picture of how visual information about motion and
      disparity is processed by human observers, and how this processing is modified by
      prolonged sensory stimulation. We were able to isolate two perceptual components:
      a separable component, supported by separate motion and disparity signals, and an
      inseparable joint component, supported by motion and disparity signals that are
      concurrently represented at the level of the same neural mechanism. Both
      components are involved in the perception of stimuli containing motion and
      disparity information in line with the known existence of corresponding neuronal
      subpopulations in visual cortex.

PMID- 18829852
TI  - The dynamics of postural sway cannot be captured using a one-segment inverted
      pendulum model: a PCA on segment rotations during unperturbed stance.
AB  - Research on unperturbed stance is largely based on a one-segment inverted
      pendulum model. Recently, an increasing number of studies report a contribution
      of other major joints to postural control. Therefore this study evaluates whether
      the conclusions originating from the research based on a one-segment model
      adequately capture postural sway during unperturbed stance. High-pass filtered
      kinematic data (cutoff frequency 1/30 Hz) obtained over 3 min of unperturbed
      stance were analyzed in different ways. Variance of joint angles was analyzed.
      Principal-component analysis (PCA) was performed on the variance of lower leg,
      upper leg, and head-arms-trunk (HAT) angles, as well as on lower leg and COM
      angle (the orientation of the line from ankle joint to center of mass). It was
      found that the variance in knee and hip joint angles did not differ from the
      variance found in the ankle angle. The first PCA component indicated that,
      generally, the upper leg and HAT segments move in the same direction as the lower
      leg with a somewhat larger amplitude. The first PCA component relating ankle
      angle variance and COM angle variance indicated that the ankle joint angle
      displacement gives a good estimate of the COM angle displacement. The second PCA
      component on the segment angles partly explains the apparent discrepancy between
      these findings because this component points to a countermovement of the HAT
      relative to the ankle joint angle. It is concluded that postural control during
      unperturbed stance should be analyzed in terms of a multiple inverted pendulum
      model.

PMID- 18829853
TI  - Temperature-dependent regulation of vocal pattern generator.
AB  - Vocalizations of Xenopus laevis are generated by central pattern generators
      (CPGs). The advertisement call of male X. laevis is a complex biphasic motor
      rhythm consisting of fast and slow trills (a train of clicks). We found that the
      trill rate of these advertisement calls is sensitive to temperature and that this
      rate modification of the vocal rhythms originates in the central pattern
      generators. In vivo the rates of fast and slow trills increased linearly with an
      increase in temperature. In vitro a similar linear relation between temperature
      and compound action potential frequency in the laryngeal nerve was found when
      fictive advertisement calls were evoked in the isolated brain. Temperature did
      not limit the contractile properties of laryngeal muscles within the frequency
      range of vocalizations. We next took advantage of the temperature sensitivity of
      the vocal CPG in vitro to localize the source of the vocal rhythms. We focused on
      the dorsal tegmental area of the medulla (DTAM), a brain stem nucleus that is
      essential for vocal production. We found that bilateral cooling of DTAM reduced
      both fast and slow trill rates. Thus we conclude that DTAM is a source of
      biphasic vocal rhythms.

PMID- 18829854
TI  - Identification of the plant for upright stance in humans: multiple movement
      patterns from a single neural strategy.
AB  - We determined properties of the plant during human upright stance using a closed
      loop system identification method originally applied to human postural control by
      another group. To identify the plant, which was operationally defined as the
      mapping from muscle activation (rectified EMG signals) to body segment angles, we
      rotated the visual scene about the axis through the subject's ankles using a sum
      of-sines stimulus signal. Because EMG signals from ankle muscles and from hip and
      lower trunk muscles showed similar responses to the visual perturbation across
      frequency, we combined EMG signals from all recorded muscles into a single plant
      input. Body kinematics were described by the trunk and leg angles in the sagittal
      plane. The phase responses of both angles to visual scene angle were similar at
      low frequencies and approached a difference of approximately 150 degrees at
      higher frequencies. Therefore we considered leg and trunk angles as separate
      plant outputs. We modeled the plant with a two-joint (ankle and hip) model of the
      body, a second-order low-pass filter from EMG activity to active joint torques,
      and intrinsic stiffness and damping at both joints. The results indicated that
      the in-phase (ankle) pattern was neurally generated, whereas the out-of-phase
      pattern was caused by plant dynamics. Thus a single neural strategy leads to
      multiple kinematic patterns. Moreover, estimated intrinsic stiffness in the model
      was insufficient to stabilize the plant.

PMID- 18829856
TI  - Prevalence and causes of visual impairment in low-middle income school children
      in Sao Paulo, Brazil.
AB  - PURPOSE: Assess prevalence and causes of vision impairment among low-middle
      income school children in Sao Paulo. METHODS: Cluster sampling was used to obtain
      a random sample of children ages 11 to 14 years from public schools (grades 5-8)
      in three districts from June to November 2005. The examination included visual
      acuity testing, ocular motility, and examination of the external eye, anterior
      segment, and media. Cycloplegic refraction and fundus examination were performed
      in children with uncorrected visual acuity 20/40 or worse in either eye. A
      principal cause of visual impairment was determined for eyes with uncorrected
      visual acuity of 20/40 or worse. RESULTS: A total of 2825 children were
      enumerated and 2441 (86.4%) were examined. The prevalence of uncorrected,
      presenting, and best-corrected visual acuity 20/40 or worse in the better eye was
      4.82%, 2.67%, and 0.41%, respectively. Spectacles were used by 144 (5.9%)
      children. Refractive error was a cause in 76.8% of children with visual
      impairment in one or both eyes; amblyopia, 11.4%; retinal disorders, 5.9%; other
      causes, 2.7%; and unexplained causes, 7.7%. Myopic visual impairment (spherical
      equivalent -0.50 D in one or both eyes) was not associated with age or grade
      level, but female sex was marginally significant (P = 0.070). Hyperopic visual
      impairment (+2.00 D or more) was not associated with age, grade level, or sex.
      CONCLUSIONS: The prevalence of reduced vision in low-middle income urban Sao
      Paulo school children was low, most of it because of uncorrected refractive
      error. Cost-effective strategies are needed to address this easily treated cause
      of vision impairment.

PMID- 18829857
TI  - Uniformity of visual acuity measures in published studies.
AB  - PURPOSE: To investigate the methods used in contemporary ophthalmic literature to
      designate visual acuity (VA). METHODS: Papers in all 2005 editions of five
      ophthalmic journals were considered. Papers were included if (1) VA, vision, or
      visual function was mentioned in the abstract and (2) if the study involved age
      related macular degeneration, cataract, or refractive surgery. If a paper was
      selected on the basis of its abstract, the full text of the paper was examined
      for information on the method of refractive correction during VA testing, type of
      chart used to measure VA, specifics concerning chart features, testing protocols,
      and data analysis and means of expressing VA in results. RESULTS: One hundred
      twenty-eight papers were included. The most common type of charts used were
      described as logMAR-based. Although most (89.8%) of the studies reported on the
      method of refractive correction during VA testing, only 58.6% gave the chart
      design, and less than 12% gave any information whatsoever on chart features or
      measurement procedures used. CONCLUSIONS: The methods used and the approach to
      analysis were rarely described in sufficient detail to allow others to replicate
      the study being reported. Sufficient detail should be given on VA measurement to
      enable others to duplicate the research. The authors suggest that charts adhering
      to Bailey-Lovie design principles always be used to measure vision in prospective
      studies and their use encouraged in clinical settings. The distinction between
      the terms logMAR, an acuity notation, and Bailey-Lovie or ETDRS as chart types
      should be adhered to more strictly.

PMID- 18829858
TI  - Retinal and optic disc findings in adolescence: a population-based OCT study.
AB  - PURPOSE: To examine the distribution of macular and peripapillary nerve fiber
      layer (NFL) thickness and optic disc parameters in early-adolescence Australian
      children and to compare these with previously reported findings in younger
      children. METHODS: The Sydney Childhood Eye Study is a population-based cross
      sectional survey of children's eye health. During 2004 and 2005, 2367 (75.3%) of
      3144 eligible year 7 students from a random cluster sample of 21 secondary
      schools in Sydney, Australia, were examined. The comprehensive eye examination
      included measurement of macular and NFL thickness and optic disc parameters by
      optical coherence tomography (StratusOCT; Carl Zeiss Meditec, Dublin, CA).
      RESULTS: Macular, NFL thickness, and optic disc parameters were normally
      distributed in early-adolescence children. Mean (+/-SD) thicknesses of the
      central 1 mm, and inner and outer macular rings were 197.4 +/- 18.7, 271.9 +/-
      15.0, and 239.5 +/- 13.5 microm, respectively. The foveal minimum thickness was
      161.6 +/- 19.9 microm. The mean (+/-SD) of average NFL thickness was 103.6 +/-
      10.6 microm. Mean (+/-SD) vertical and horizontal disc diameters were 1.88 +/-
      0.25 and 1.61 +/- 0.20 mm; corresponding cup-to-disc ratios were 0.39 +/- 0.14
      and 0.44 +/- 0.16. There were minimal sex differences in these parameters after
      adjustment for multiple ocular and demographic variables. Compared with
      parameters in the childhood group, the macula was generally slightly thicker and
      the optic disc slightly larger in the early-adolescence group, although
      differences between these two age groups were small. The foveal minimum and NFL
      thickness were similar between the two age groups. CONCLUSIONS: This study
      describes the normative distribution of macular, NFL, and optic disc parameters
      in early-adolescence children and also demonstrates minimal differences between
      the sexes. These parameters were also largely unchanged between early childhood
      and early adolescence, although the comparisons were made in two cross-sectional
      samples, rather than from longitudinal measures.

PMID- 18829859
TI  - Inhibition of corneal neovascularization by blocking the angiotensin II type 1
      receptor.
AB  - PURPOSE: To determine the role of angiotensin II type 1 receptor (AT1R) signaling
      in corneal neovascularization. METHODS: Corneal neovascularization was induced by
      suturing 10-0 nylon 1 mm away from limbal vessels in C57 BJ6 mice.
      Angiotensinogen and its receptor (AT1R) gene expression levels were evaluated by
      semiquantitative reverse transcription-polymerase chain reaction (RT-PCR). The
      expression of angiotensin II (Ang2) and AT1R was confirmed by Western blotting
      and immunohistochemistry. To investigate the function of Ang2 in corneal
      neovascularization, infiltrating macrophages in vascularized corneas and the
      neovascularized area were investigated after intraperitoneal injection of an AT1R
      antagonist (telmisartan, 10 mg/kg). Further, corneal mRNA of VEGF, MCP-1, IL-6,
      ICAM-1, and TNF-alpha was examined in control and telmisartan-treated mice.
      RESULTS: Ang2 and AT1R markedly increased in the neovascularized corneas compared
      with normal corneas. Ang2 and AT1R were expressed in epithelium and stromal cells
      (vascular endothelium, infiltrating leukocytes, and keratocytes) in
      neovascularized cornea at protein levels and were weakly detected in normal
      corneal epithelium. Infiltrating macrophages were reduced in telmisartan-treated
      mice on day 7 after suturing. Neovascularized area in the cornea of telmisartan
      treated mice was 70% smaller than that of control mice on day 7 after suturing. A
      PPAR-gamma antagonist partially, but significantly, reversed the suppressive
      effect of telmisartan on induction of corneal neovascularization. The expression
      of VEGF, MCP-1, IL-6, and ICAM-1 was significantly inhibited in telmisartan
      treated mice. CONCLUSIONS: These findings indicate that Ang2, abundantly
      expressed in neovascularized corneas, has a significant role in inflammation
      related driven corneal neovascularization. AT1R may be a therapeutic target for
      the suppression of corneal neovascularization.

PMID- 18829860
TI  - Endoscopic vitrectomy improves outcomes of Seoul-type keratoprosthesis exchange
      in rabbit model.
AB  - PURPOSE: To investigate the efficacy of an endoscopic vitrectomy in Seoul-type
      keratoprosthesis (S-Kpro) exchange procedures. METHODS: Nine S-Kpro-implanted
      rabbit eyes were enrolled in the S-Kpro exchange. Six eyes underwent an
      antecedent vitrectomy by an endoscopic system and then the S-Kpro exchange
      (endoscopy group). In the other three eyes, previously placed S-Kpros were
      removed, and a conventional vitrectomy was performed using the Eckardt
      keratoprosthesis, followed by an implantation of new S-Kpros (Eckardt group). All
      eyes were evaluated with slit lamp biomicroscopy and ultrasonography weekly to
      evaluate the time up to the development of the total retinal detachment (RD).
      RESULTS: Vitreous traction membranes were found around the prolene haptics of the
      fixation sites in all the S-Kpro implanted rabbits; they were excised precisely
      through an endoscopic view in the endoscopy group. The mean survival time up to
      the RD development was 9.75 +/- 4.70 weeks in the endoscopy group. In contrast,
      total retinal detachment or dialysis over 180 degrees developed during surgery in
      all three eyes in the Eckardt group. CONCLUSIONS: Antecedent endoscopic
      vitrectomy was safe and effective for the S-Kpro exchange in a rabbit model by
      removing the vitreous traction near the haptics before the exchange procedures.

PMID- 18829861
TI  - Remodeling retinal neovascularization by ALK1 gene transfection in vitro.
AB  - PURPOSE: To explore a novel strategy for balancing retinal neovascularization by
      assessing the role activin-like kinase receptor 1 (ALK1) plays in
      neovascularization in vascular endothelial growth factor (VEGF)-stimulated human
      retinal capillary endothelial cells (HRCECs). METHODS: HRCECs were transfected
      with an ALK1 gene-encoding plasmid or a pSIREN-ALK1 RNAi vector and stimulated
      with VEGF. The mRNA and protein expression levels of ALK1, occludin, ANG2, and
      ALK5 were evaluated by real-time PCR and/or Western blot analysis. Microscopy
      techniques and flow cytometry were used to assess the effects of enhanced levels
      of ALK1 on migration and proliferation and the formation of tubelike structures
      of HRCECs. RESULTS: The level of ALK1 in ALK1-transfected cells was significantly
      increased compared with that in control cells. ALK1-transfected cells exhibited
      increased expression of occludin and decreased expression of ANG2 and ALK5,
      compared with expression in the control cells. HRCECs transfected with pSIREN
      ALK1 RNAi exhibited decreased expression of ALK1 and occludin and increased
      expression of ANG2 and ALK5 compared with the control cells. Transfection with
      ALK1 affected the migration and proliferation of VEGF-stimulated HRCECs. ALK1
      also inhibited the formation of endothelial tubelike structures, but did allow
      the formation of entire vessel structures. CONCLUSIONS: Overexpression of ALK1
      promoted remodeling of newly formed blood vessels and prevented further
      angiogenesis. These findings provide insight into the control of retinal
      neovascularization and demonstrate a novel strategy for maintaining a stable
      phase of vessel formation, allowing for effective retinal neovascularization
      without the common adverse effects seen in patients with diabetic retinopathy,
      age-related macular degeneration, and retinal vein occlusion.

PMID- 18829862
TI  - Sentan: a novel specific component of the apical structure of vertebrate motile
      cilia.
AB  - Human respiratory and oviductal cilia have specific apical structures
      characterized by a narrowed distal portion and a ciliary crown. These structures
      are conserved among vertebrates that have air respiration systems; however, the
      molecular components of these structures have not been defined, and their
      functions are unknown. To identify the molecular component(s) of the cilia apical
      structure, we screened EST libraries to identify gene(s) that are exclusively
      expressed in ciliated tissues, are transcriptionally up-regulated during in vitro
      ciliogenesis, and are not expressed in testis (because sperm flagella have no
      such apical structures). One of the identified gene products, named sentan, was
      localized to the distal tip region of motile cilia. Using anti-sentan polyclonal
      antibodies and electron microscopy, sentan was shown to localize exclusively to
      the bridging structure between the cell membrane and peripheral singlet
      microtubules, which specifically exists in the narrowed distal portion of cilia.
      Exogenously expressed sentan showed affinity for the membrane protrusions, and a
      protein-lipid binding assay revealed that sentan bound to phosphatidylserine.
      These findings suggest that sentan is the first molecular component of the
      ciliary tip to bridge the cell membrane and peripheral singlet microtubules,
      making the distal portion of the cilia narrow and stiff to allow for better
      airway clearance or ovum transport.

PMID- 18829863
TI  - Ribosome-associated complex binds to ribosomes in close proximity of Rpl31 at the
      exit of the polypeptide tunnel in yeast.
AB  - Ribosome-associated complex (RAC) consists of the Hsp40 homolog Zuo1 and the
      Hsp70 homolog Ssz1. The chaperone participates in the biogenesis of newly
      synthesized polypeptides. Here we have identified yeast Rpl31, a component of the
      large ribosomal subunit, as a contact point of RAC at the polypeptide tunnel
      exit. Rpl31 is encoded by RPL31a and RPL31b, two closely related genes. Delta
      rpl31a Delta rpl31b displayed slow growth and sensitivity to low as well as high
      temperatures. In addition, Delta rpl31a Delta rpl31b was highly sensitive toward
      aminoglycoside antibiotics and suffered from defects in translational fidelity.
      With the exception of sensitivity at elevated temperature, the phenotype
      resembled yeast strains lacking one of the RAC subunits or Rpl39, another protein
      localized at the tunnel exit. Defects of Delta rpl31a Delta rpl31b Delta zuo1 did
      not exceed that of Delta rpl31a Delta rpl31b or Delta zuo1. However, the combined
      deletion of RPL31a, RPL31b, and RPL39 was lethal. Moreover, RPL39 was a multicopy
      suppressor, whereas overexpression of RAC failed to rescue growth defects of
      Delta rpl31a Delta rpl31b. The findings are consistent with a model in that Rpl31
      and Rpl39 independently affect a common ribosome function, whereas Rpl31 and RAC
      are functionally interdependent. Rpl31, while not essential for binding of RAC to
      the ribosome, might be involved in proper function of the chaperone complex.

PMID- 18829864
TI  - Self-interaction is critical for Atg9 transport and function at the phagophore
      assembly site during autophagy.
AB  - Autophagy is the degradation of a cell's own components within lysosomes (or the
      analogous yeast vacuole), and its malfunction contributes to a variety of human
      diseases. Atg9 is the sole integral membrane protein required in formation of the
      initial sequestering compartment, the phagophore, and is proposed to play a key
      role in membrane transport; the phagophore presumably expands by vesicular
      addition to form a complete autophagosome. It is not clear through what mechanism
      Atg9 functions at the phagophore assembly site (PAS). Here we report that Atg9
      molecules self-associate independently of other known autophagy proteins in both
      nutrient-rich and starvation conditions. Mutational analyses reveal that self
      interaction is critical for anterograde transport of Atg9 to the PAS. The ability
      of Atg9 to self-interact is required for both selective and nonselective
      autophagy at the step of phagophore expansion at the PAS. Our results support a
      model in which Atg9 multimerization facilitates membrane flow to the PAS for
      phagophore formation.

PMID- 18829865
TI  - Munc18a scaffolds SNARE assembly to promote membrane fusion.
AB  - Munc18a is an SM protein required for SNARE-mediated fusion. The molecular
      details of how Munc18a acts to enhance neurosecretion have remained elusive.
      Here, we use in vitro fusion assays to characterize how specific interactions
      between Munc18a and the neuronal SNAREs enhance the rate and extent of fusion. We
      show that Munc18a interacts directly and functionally with the preassembled t
      SNARE complex. Analysis of Munc18a point mutations indicates that Munc18a
      interacts with helix C of the Syntaxin1a NRD in the t-SNARE complex. Replacement
      of the t-SNARE SNAP25b with yeast Sec9c had little effect, suggesting that
      Munc18a has minimal contact with SNAP25b within the t-SNARE complex. A chimeric
      Syntaxin built of the Syntaxin1a NRD and the H3 domain of yeast Sso1p and paired
      with Sec9c eliminated stimulation of fusion, suggesting that Munc18a/Syntaxin1a
      H3 domain contacts are important. Additionally, a Syntaxin1A mutant lacking a
      flexible linker region that allows NRD movement abolished stimulation of fusion.
      These experiments suggest that Munc18a binds to the Syntaxin1a NRD and H3 domain
      within the assembled t-SNARE complex, positioning them for productive VAMP2
      binding. In this capacity, Munc18a serves as a platform for trans-SNARE complex
      assembly that facilitates efficient SNARE-mediated membrane fusion.

PMID- 18829866
TI  - Farnesylation of Ydj1 is required for in vivo interaction with Hsp90 client
      proteins.
AB  - Ydj1 of Saccharomyces cerevisiae is an abundant cytosolic Hsp40, or J-type,
      molecular chaperone. Ydj1 cooperates with Hsp70 of the Ssa family in the
      translocation of preproteins to the ER and mitochondria and in the maturation of
      Hsp90 client proteins. The substrate-binding domain of Ydj1 directly interacts
      with steroid receptors and is required for the activity of diverse Hsp90
      dependent client proteins. However, the effect of Ydj1 alteration on client
      interaction was unknown. We analyzed the in vivo interaction of Ydj1 with the
      protein kinase Ste11 and the glucocorticoid receptor. Amino acid alterations in
      the proposed client-binding domain or zinc-binding domain had minor effects on
      the physical interaction of Ydj1 with both clients. However, alteration of the
      carboxy-terminal farnesylation signal disrupted the functional and physical
      interaction of Ydj1 and Hsp90 with both clients. Similar effects were observed
      upon deletion of RAM1, which encodes one of the subunits of yeast
      farnesyltransferase. Our results indicate that farnesylation is a major factor
      contributing to the specific requirement for Ydj1 in promoting proper regulation
      and activation of diverse Hsp90 clients.

PMID- 18829867
TI  - The scaffold protein POSH regulates axon outgrowth.
AB  - How scaffold proteins integrate signaling pathways with cytoskeletal components
      to drive axon outgrowth is not well understood. We report here that the
      multidomain scaffold protein Plenty of SH3s (POSH) regulates axon outgrowth.
      Reduction of POSH function by RNA interference (RNAi) enhances axon outgrowth in
      differentiating mouse primary cortical neurons and in neurons derived from mouse
      P19 cells, suggesting POSH negatively regulates axon outgrowth. Complementation
      analysis reveals a requirement for the third Src homology (SH) 3 domain of POSH,
      and we find that the actomyosin regulatory protein Shroom3 interacts with this
      domain of POSH. Inhibition of Shroom3 expression by RNAi leads to increased
      process lengths, as observed for POSH RNAi, suggesting that POSH and Shroom
      function together to inhibit process outgrowth. Complementation analysis and
      interference of protein function by dominant-negative approaches suggest that
      Shroom3 recruits Rho kinase to inhibit process outgrowth. Furthermore, inhibition
      of myosin II function reverses the POSH or Shroom3 RNAi phenotype, indicating a
      role for myosin II regulation as a target of the POSH-Shroom complex.
      Collectively, these results suggest that the molecular scaffold protein POSH
      assembles an inhibitory complex that links to the actin-myosin network to
      regulate neuronal process outgrowth.

PMID- 18829868
TI  - Galectin-7 in the control of epidermal homeostasis after injury.
AB  - Galectins, a family of beta-galactoside binding lectins, have recently emerged as
      novel regulators of tissue homeostasis. Galectin-7 is predominantly expressed in
      stratified epithelia, especially in epidermis. We report here the generation of
      galectin-7-deficient mice that are viable and do not display phenotypical
      abnormalities in skin structure or expression of epidermal markers. However,
      these mice show unique defects in the maintenance of epidermal homeostasis in
      response to environmental challenges. First, after UVB irradiation in vivo, the
      apoptotic response is prematurely triggered and lasts longer in the mutant
      epidermis. This result contrasts with the proapoptotic role that had been
      proposed for galectin-7. Second, wound-healing experiments in vivo revealed that
      galectin-7-deficient mice displayed a reduced reepithelialization potential
      compared with wild-type littermates. This effect could be attributed to a defect
      in cell migration. Because galectin-7 is located in the podosomes of
      keratinocytes migrating out of skin explants in culture, we propose that this
      glycan-binding protein may directly influence cell/extracellular matrix
      interactions. Finally, we also detected an unexpected intense hyperproliferative
      reaction consecutive to both types of stress in galectin-7-deficient mice.
      Together, these studies provide the first genetic evidence showing that galectin
      7 can modulate keratinocyte apoptosis, proliferation, and migration during skin
      repair.

PMID- 18829869
TI  - Plasma melatonin circadian rhythm disturbances during pregnancy and postpartum in
      depressed women and women with personal or family histories of depression.
AB  - OBJECTIVE: The purpose of this study was to test the hypothesis that disturbances
      in levels of plasma melatonin differentiate pregnant and postpartum women with
      major depression from matched pregnant and postpartum healthy comparison women.
      METHOD: Participants were 25 pregnant women (10 with major depression, 15
      healthy) and 24 postpartum women (13 with major depression, 11 healthy). Healthy
      comparison women were matched on the number of weeks pregnant or postpartum.
      Plasma melatonin levels for each subject were measured every 30 minutes, in dim
      light (<30 lux), from 6:00 p.m. to 11:00 a.m. The values of plasma melatonin
      levels were log-transformed, and calculations were determined for the following
      measures: baseline and synthesis onset and offset times, duration, peak
      concentration, and area under the curve. Groups were compared by analyses of
      covariance, with age, number of weeks pregnant or postpartum, breast-feeding
      status, and body mass index as covariates. RESULTS: Morning melatonin levels from
      2:00 a.m. to 11:00 a.m. were significantly lower in pregnant women with major
      depression relative to healthy pregnant women. However, these levels were
      significantly higher in postpartum women with major depression across time
      intervals relative to postpartum healthy women. Pregnant but not postpartum women
      with a personal or family history of depression, regardless of their current
      diagnosis, had significantly earlier melatonin synthesis and baseline offset
      times relative to women without a family history of depression. In pregnant
      healthy women but not pregnant women with major depression, melatonin levels
      increased during the course of pregnancy. This association was not found among
      postpartum women with major depression or postpartum healthy women. CONCLUSIONS:
      Plasma nocturnal melatonin concentrations, particularly during morning hours,
      were lower in depressed pregnant women but elevated in depressed postpartum women
      relative to matched healthy comparison women. In addition, melatonin timing
      measures were advanced in pregnant women with a personal or family history of
      depression. These findings implicate disturbances in the regulation of the
      melatonin generating system in pregnancy and postpartum depression.

PMID- 18829870
TI  - Strong evidence for a novel schizophrenia risk locus on chromosome 1p31.1 in
      homogeneous pedigrees from Tamil Nadu, India.
AB  - OBJECTIVE: The study of ethnically homogeneous populations may help to identify
      schizophrenia risk loci. The authors conducted a genomewide linkage scan for
      schizophrenia in an Indian population. METHOD: Participants were 441 individuals
      (262 affected probands and siblings) who were recruited primarily from one
      ethnically homogeneous group, the Tamil Brahmin caste, although individuals from
      other geographically proximal castes also participated. Genotyping of 124
      affected sibling pair pedigrees was performed with 402 short tandem repeat
      polymorphisms. Linkage analyses were conducted using nonparametric exponential
      LOD (logarithm of the odds ratio for linkage) scores and parametric heterogeneity
      LOD scores. Parametric heterogeneity scores were calculated using simple dominant
      and recessive models, correcting for multiple statistics. The data were examined
      for evidence of consanguinity. Genomewide significance levels were determined
      using 10,000 gene dropping simulations. RESULTS: These findings revealed
      genomewide significant linkage to chromosome 1p31.1, through the use of both
      exponential and heterogeneity LOD scores, incorporating correction for multiple
      statistics and mild consanguinity. The estimated sibling recurrence risk
      associated with this putative locus was 1.95. Analysis for heterogeneity LOD
      scores also detected suggestive linkage to chromosomes 13q22.1 and 16q12.2. Using
      117 tag single nucleotide polymorphisms (SNPs), family-based association analyses
      of phosphodiesterase 4B (PDE4B), the closest schizophrenia candidate gene,
      detected no convincing evidence of association, suggesting that the chromosome 1
      peak represents a novel risk locus. CONCLUSIONS: This is the first study-to the
      authors' knowledge-to report significant linkage of schizophrenia to chromosome
      1p31.1. Further investigation of this chromosome region in diverse populations is
      warranted to identify underlying sequence variants.

PMID- 18829871
TI  - Disorder-specific dissociation of orbitofrontal dysfunction in boys with pure
      conduct disorder during reward and ventrolateral prefrontal dysfunction in boys
      with pure ADHD during sustained attention.
AB  - OBJECTIVE: Among children, attention deficit hyperactivity disorder (ADHD) and
      conduct disorder are often comorbid and overlap clinically. Neuropsychological
      evidence suggests that children with conduct disorder demonstrate more prominent
      motivational problems and children with ADHD demonstrate more prominent attention
      deficits relative to healthy comparison subjects. The purpose of the present
      study was to investigate disorder-specific abnormalities in the neurobiological
      correlates of motivation and sustained attention in children and adolescents with
      pure conduct disorder and children and adolescents with pure ADHD. METHOD:
      Participants were male pediatric patients, ages 9-16 years, with noncomorbid
      conduct disorder (N=14) and noncomorbid ADHD, combined hyperactive-inattentive
      subtype (N=18), as well as age- and IQ-matched healthy comparison subjects
      (N=16). Both patient groups were medication naive. Event-related functional
      magnetic resonance imaging (fMRI) was used to compare brain activation during a
      rewarded continuous performance task that measured sustained attention as well as
      the effects of reward on performance. RESULTS: During the sustained attention
      condition, patients with noncomorbid ADHD showed significantly reduced activation
      in the bilateral ventrolateral prefrontal cortex and increased activation in the
      cerebellum relative to patients with noncomorbid conduct disorder and healthy
      comparison subjects. Patients with noncomorbid conduct disorder showed decreased
      activation in paralimbic regions of the insula, hippocampus, and anterior
      cingulate as well as the cerebellum relative to patients with noncomorbid ADHD
      and healthy comparison subjects. However, during the reward condition, patients
      with noncomorbid conduct disorder showed disorder-specific underactivation in the
      right orbitofrontal cortex, while patients with noncomorbid ADHD showed disorder
      specific dysfunction in the posterior cingulate gyrus. CONCLUSIONS: The findings
      revealed a process-related dissociation of prefrontal dysfunction in ADHD and
      conduct disorder patients. Attention-related dysfunction in the ventrolateral
      prefrontal cortex was seen in ADHD patients, and reward-related dysfunction in
      the orbitofrontal cortex was seen in conduct disorder patients. These findings,
      together with the pattern of paralimbic dysfunction demonstrated among children
      with conduct disorder during sustained attention, support theories of
      abnormalities in orbitofrontal-paralimbic motivation networks in individuals with
      conduct disorder and, in contrast, ventrolateral fronto-cerebellar attention
      network dysfunction in individuals with ADHD.

PMID- 18829872
TI  - The role of interpersonal and social rhythm therapy in improving occupational
      functioning in patients with bipolar I disorder.
AB  - OBJECTIVE: Recent studies demonstrate the poor psychosocial outcomes associated
      with bipolar disorder. Occupational functioning, a key indicator of psychosocial
      disability, is often severely affected by the disorder. The authors describe the
      effect of acute treatment with interpersonal and social rhythm therapy on
      occupational functioning over a period of approximately 2.5 years. METHOD:
      Patients with bipolar I disorder were randomly assigned to receive either acute
      and maintenance interpersonal and social rhythm therapy, acute and maintenance
      intensive clinical management, acute interpersonal and social rhythm therapy and
      maintenance intensive clinical management, or acute intensive clinical management
      and maintenance interpersonal and social rhythm therapy, all with appropriate
      pharmacotherapy. Occupational functioning was measured with the UCLA Social
      Attainment Scale at baseline, at the end of acute treatment, and after 1 and 2
      years of maintenance treatment. RESULTS: The main effect of treatment did not
      reach conventional levels of statistical significance; however, the authors
      observed a significant time by initial treatment interaction. Participants
      initially assigned to interpersonal and social rhythm therapy showed more rapid
      improvement in occupational functioning than those initially assigned to
      intensive clinical management, primarily accounted for by greater improvement in
      occupational functioning during the acute treatment phase. At the end of 2 years
      of maintenance treatment, there were no differences between the treatment groups.
      A gender effect was also observed, with women who initially received
      interpersonal and social rhythm therapy showing more marked and rapid
      improvement. There was no effect of maintenance treatment assignment on
      occupational functioning outcomes. CONCLUSIONS: In this study, interpersonal and
      social rhythm therapy, with its emphasis on amelioration of interpersonal and
      role functioning, improved occupational functioning significantly more rapidly
      than did a psychoeducational and supportive approach with no such emphasis on
      functional capacities.

PMID- 18829873
TI  - Association of the KIAA0319 dyslexia susceptibility gene with reading skills in
      the general population.
AB  - OBJECTIVE: The authors previously identified a haplotype on chromosome 6p22
      defined by three single-nucleotide polymorphisms (SNPs) that was associated with
      dyslexia (reading disability) in two independent samples of families that
      included at least one sibling with severe reading impairment. The authors also
      showed that this haplotype is associated with a reduction in expression of the
      KIAA0319 gene. In addition, a completely independent study detected an
      association between KIAA0319 markers and reading disability. In the current
      study, the authors tested whether the KIAA0319 gene influences reading skills in
      the general population, rather than having an effect restricted to reading
      disability. METHOD: The authors genotyped four SNPs that previously showed
      association with reading disability in the population of 7-9-year-old children in
      the Avon Longitudinal Study of Parents and Children (ALSPAC), a large
      longitudinal cohort for which reading-related phenotypes were available for more
      than 6,000 individuals. The authors conducted quantitative analysis for both
      single markers and haplotypes. RESULTS: The rs2143340 SNP, which effectively tags
      the three-SNP risk haplotype, was significantly associated with a test for
      reading ability. The risk haplotype itself also showed association with poor
      reading performance, and as in previous research, the association was stronger
      when the analysis was controlled for IQ. CONCLUSIONS: These results both support
      a role of the KIAA0319 gene in the development of dyslexia and suggest that this
      gene influences reading ability in the general population. Moreover, the data
      implicate the three-SNP haplotype and its tagging SNP rs2143340 as genetic risk
      factors for poor reading performance.

PMID- 18829874
TI  - The perplexities of conducting randomized, double-blind, placebo-controlled
      treatment trials in anorexia nervosa patients.

PMID- 18829875
TI  - A developmental and evolutionary perspective on obsessive-compulsive disorder:
      whence and whither compulsive hoarding?

PMID- 18829876
TI  - Bipolar drug development: are we getting closer to the real world?

PMID- 18829877
TI  - Developmental considerations for diagnosing PTSD and acute stress disorder in
      preschool and school-age children.

PMID- 18829878
TI  - Issues for DSM-V: unintended consequences of small changes: the case of
      paraphilias.

PMID- 18829879
TI  - Putting housing first, making housing last: housing policy for persons with
      severe mental illness.

PMID- 18829881
TI  - Quality improvement of psychiatric care: challenges of emergency psychiatry.

PMID- 18829880
TI  - Drug interactions and pharmacogenomics in the treatment of breast cancer and
      depression.

PMID- 18829882
TI  - Theodor Lipps and the concept of empathy: 1851-1914.

PMID- 18829883
TI  - Presidential address: our voice in action: advancing science, care, and our
      profession.

PMID- 18829887
TI  - Effectiveness of adjunctive STEPPS group treatment in borderline personality
      disorder patients.

PMID- 18829888
TI  - Developing supportive psychotherapy as evidence-based treatment.

PMID- 18829889
TI  - Supportive psychotherapy: the nature of the connection to patients.

PMID- 18829890
TI  - Aggression, suicide, and lithium treatment.

PMID- 18829891
TI  - Cannabis and the course of schizophrenia.

PMID- 18829892
TI  - Divided doses for methadone maintenance.

PMID- 18829893
TI  - Short-chain ubiquitination is associated with the degradation rate of a cell
      surface-resident bile salt export pump (BSEP/ABCB11).
AB  - The reduced expression of the bile salt export pump (BSEP/ABCB11) at the
      canalicular membrane is associated with cholestasis-induced hepatotoxicity due to
      the accumulation of bile acids in hepatocytes. We demonstrated previously that 4
      phenylbutyrate (4PBA) treatment, a U.S. Food and Drug Administration-approved
      drug for the treatment of urea cycle disorders, induces the cell-surface
      expression of BSEP by prolonging the degradation rate of cell-surface-resident
      BSEP. On the other hand, BSEP mutations, E297G and D482G, found in progressive
      familial intrahepatic cholestasis type 2 (PFIC2), reduced it by shortening the
      degradation rate of cell-surface-resident BSEP. Therefore, to help the
      development of the medical treatment of cholestasis, we investigated the
      underlying mechanism by which 4PBA and PFIC2-type mutations affect the BSEP
      degradation from cell surface, focusing on short-chain ubiquitination. In Madin
      Darby canine kidney II (MDCK II) cells expressing BSEP and rat canalicular
      membrane vesicles, the molecular mass of the mature form of BSEP/Bsep shifted
      from 170 to 190 kDa after ubiquitin modification (molecular mass, 8 kDa).
      Ubiquitination susceptibility of BSEP/Bsep was reduced in vitro and in vivo by
      4PBA treatment and, conversely, was enhanced by BSEP mutations E297G and D482G.
      Moreover, biotin-labeling studies using MDCK II cells demonstrated that the
      degradation of cell-surface-resident chimeric protein fusing ubiquitin to BSEP
      was faster than that of BSEP itself. In conclusion, BSEP/Bsep is modified with
      two to three ubiquitins, and its ubiquitination is modulated by 4PBA treatment
      and PFIC2-type mutations. Modulation of short-chain ubiquitination can regulate
      the change in the degradation rate of cell-surface-resident BSEP by 4PBA
      treatment and PFIC2-type mutations.

PMID- 18829895
TI  - Short-term effects of thyroid hormones on Na+-K+-ATPase activity of chick embryo
      hepatocytes during development: focus on signal transduction.
AB  - Nongenomic effects of thyroid hormones on Na+-K+-ATPase activity were studied in
      chick embryo hepatocytes at two different developmental stages, 14 and 19 days of
      embryonal age, and the signal transduction pathways involved were characterized.
      Our data showed the following. 1) 3,5,3'-Triiodo-L-thyronine (T3) and 3,5-diiodo
      L-thyronine (3,5-T2) rapidly induced a transient inhibitory effect on the Na+-K+
      ATPase; the extent and duration depended on the developmental age of the cells.
      2) 3,5-T2 behaved as a true hormone and fully mimicked the effect of T3. 3)
      Thyroxine had no effect at any of the developmental stages. 4) The inhibition of
      Na+-K+-ATPase was mediated by activation of protein kinase A, protein kinase C,
      and phosphoinositide 3-kinase, suggesting several modes of modulation of ATPase
      activity through phosphorylation at different sites. 5) The MAPK pathway did not
      seem to be involved in the early phase of hormone treatment. 6) The nonpermeant
      analog T3-agarose inhibited Na+-K+-ATPase activity in the same way as T3,
      confirming that hormone signaling initiated at a receptor on the plasma membrane.
      From these results, it can be concluded that the cell response mechanisms change
      rapidly and drastically within the early phase of embryo growth. The differences
      found at the two stages probably reflect the different roles of thyroid hormones
      during development and differentiation.

PMID- 18829894
TI  - Role of NADH/NAD+ transport activity and glycogen store on skeletal muscle energy
      metabolism during exercise: in silico studies.
AB  - Skeletal muscle can maintain ATP concentration constant during the transition
      from rest to exercise, whereas metabolic reaction rates may increase
      substantially. Among the key regulatory factors of skeletal muscle energy
      metabolism during exercise, the dynamics of cytosolic and mitochondrial NADH and
      NAD+ have not been characterized. To quantify these regulatory factors, we have
      developed a physiologically based computational model of skeletal muscle energy
      metabolism. This model integrates transport and reaction fluxes in distinct
      capillary, cytosolic, and mitochondrial domains and investigates the roles of
      mitochondrial NADH/NAD+ transport (shuttling) activity and muscle glycogen
      concentration (stores) during moderate intensity exercise (60% maximal O2
      consumption). The underlying hypothesis is that the cytosolic redox state
      (NADH/NAD+) is much more sensitive to a metabolic disturbance in contracting
      skeletal muscle than the mitochondrial redox state. This hypothesis was tested by
      simulating the dynamic metabolic responses of skeletal muscle to exercise while
      altering the transport rate of reducing equivalents (NADH and NAD+) between
      cytosol and mitochondria and muscle glycogen stores. Simulations with optimal
      parameter estimates showed good agreement with the available experimental data
      from muscle biopsies in human subjects. Compared with these simulations, a 20%
      increase (or approximately 20% decrease) in mitochondrial NADH/NAD+ shuttling
      activity led to an approximately 70% decrease (or approximately 3-fold increase)
      in cytosolic redox state and an approximately 35% decrease (or approximately 25%
      increase) in muscle lactate level. Doubling (or halving) muscle glycogen
      concentration resulted in an approximately 50% increase (or approximately 35%
      decrease) in cytosolic redox state and an approximately 30% increase (or
      approximately 25% decrease) in muscle lactate concentration. In both cases,
      changes in mitochondrial redox state were minimal. In conclusion, the model
      simulations of exercise response are consistent with the hypothesis that
      mitochondrial NADH/NAD+ shuttling activity and muscle glycogen stores affect
      primarily the cytosolic redox state. Furthermore, muscle lactate production is
      regulated primarily by the cytosolic redox state.

PMID- 18829896
TI  - Measuring ion transport activities in Xenopus oocytes using the ion-trap
      technique.
AB  - The ion-trap technique is an experimental approach allowing measurement of
      changes in ionic concentrations within a restricted space (the trap) comprised of
      a large-diameter ion-selective electrode apposed to a voltage-clamped Xenopus
      laevis oocyte. The technique is demonstrated with oocytes expressing the
      Na(+)/glucose cotransporter (SGLT1) using Na(+)- and H(+)-selective electrodes
      and with the electroneutral H(+)/monocarboxylate transporter (MCT1). In SGLT1
      expressing oocytes, bath substrate diffused into the trap within 20 s,
      stimulating Na(+)/glucose influx, which generated a measurable decrease in the
      trap Na(+) concentration ([Na(+)](T)) by 0.080 +/- 0.009 mM. Membrane
      hyperpolarization produced a further decrease in [Na(+)](T), which was
      proportional to the increased cotransport current. In a Na(+)-free, weakly
      buffered solution (pH 5.5), H(+) drives glucose transport through SGLT1, and this
      was monitored with a H(+)-selective electrode. Proton movements can also be
      clearly detected on adding lactate to an oocyte expressing MCT1 (pH 6.5). For
      SGLT1, time-dependent changes in [Na(+)](T) or [H(+)](T) were also detected
      during a membrane potential pulse (150 ms) in the presence of substrate. In the
      absence of substrate, hyperpolarization triggered rapid reorientation of SGLT1
      cation binding sites, accompanied by cation capture from the trap. The resulting
      change in [Na(+)](T) or [H(+)](T) is proportional to the pre-steady-state charge
      movement. The ion-trap technique can thus be used to measure steady-state and pre
      steady-state transport activities and provides new opportunities for studying
      electrogenic and electroneutral ion transport mechanisms.

PMID- 18829897
TI  - Inhibition of Na+/H+ exchanger enhances low pH-induced L-selectin shedding and
      beta2-integrin surface expression in human neutrophils.
AB  - Ischemia-reperfusion injury is a common pathological occurrence causing tissue
      damage in heart attack and stroke. Entrapment of neutrophils in the vasculature
      during ischemic events has been implicated in this process. In this study, we
      examine the effects that lactacidosis and consequent reductions in intracellular
      pH (pH(i)) have on surface expression of adhesion molecules on neutrophils. When
      human neutrophils were exposed to pH 6 lactate, there was a marked decrease in
      surface L-selectin (CD62L) levels, and the decrease was significantly enhanced by
      inclusion of Na(+)/H(+) exchanger (NHE) inhibitor 5-(N,N-hexamethylene)amiloride
      (HMA). Similar effects were observed when pH(i) was reduced while maintaining
      normal extracellular pH, by using an NH(4)Cl prepulse followed by washes and
      incubation in pH 7.4 buffer containing NHE inhibitors [HMA, cariporide, or 5-(N,N
      dimethyl)amiloride (DMA)]. The amount of L-selectin shedding induced by different
      concentrations of NH(4)Cl in the prepulse correlated with the level of
      intracellular acidification with an apparent pK of 6.3. In contrast, beta(2)
      integrin (CD11b and CD18) was only slightly upregulated in the low-pH(i)
      condition and was enhanced by NHE inhibition to a much lesser extent. L-selectin
      shedding was prevented by treating human neutrophils with inhibitors of
      extracellular metalloproteases (RO-31-9790 and KD-IX-73-4) or with inhibitors of
      intracellular signaling via p38 MAP kinase (SB-203580 and SB-239063), implying a
      transmembrane effect of pH(i). Taken together, these data suggest that the
      ability of NHE inhibitors such as HMA to reduce ischemia-reperfusion injury may
      be related to the nearly complete removal of L-selectin from the neutrophil
      surface.

PMID- 18829898
TI  - Genome-wide RNAi screen and in vivo protein aggregation reporters identify
      degradation of damaged proteins as an essential hypertonic stress response.
AB  - The damaging effects of hypertonic stress on cellular proteins are poorly
      defined, and almost nothing is known about the pathways that detect and repair
      hypertonicity-induced protein damage. To begin addressing these problems, we
      screened approximately 19,000 Caenorhabditis elegans genes by RNA interference
      (RNAi) feeding and identified 40 that are essential for survival during acute
      hypertonic stress. Half (20 of 40) of these genes encode proteins that function
      to detect, transport, and degrade damaged proteins, including components of the
      ubiquitin-proteasome system, endosomal sorting complexes, and lysosomes. High
      molecular-weight ubiquitin conjugates increase during hypertonic stress,
      suggesting a global change in the ubiquitinylation state of endogenous proteins.
      Using a polyglutamine-containing fluorescent reporter, we demonstrate that cell
      shrinkage induces rapid protein aggregation in vivo and that many of the genes
      that are essential for survival during hypertonic stress function to prevent
      accumulation of aggregated proteins. High levels of urea, a strong protein
      denaturant, do not cause aggregation, suggesting that factors such as
      macromolecular crowding also contribute to protein aggregate formation during
      cell shrinkage. Acclimation of C. elegans to mild hypertonicity dramatically
      increases the osmotic threshold for protein aggregation, demonstrating that
      protein aggregation-inhibiting pathways are activated by osmotic stress. Our
      studies demonstrate that hypertonic stress induces protein damage in vivo and
      that detection and degradation of damaged proteins are essential mechanisms for
      survival under hypertonic conditions.

PMID- 18829899
TI  - Visualizing the temporal effects of vasoconstrictors on PKC translocation and
      Ca2+ signaling in single resistance arterial smooth muscle cells.
AB  - Arterial smooth muscle (ASM) contraction plays a critical role in regulating
      blood distribution and blood pressure. Vasoconstrictors activate cell surface
      receptors to initiate signaling cascades involving increased intracellular Ca(2+)
      concentration ([Ca(2+)](i)) and recruitment of protein kinase C (PKC), leading to
      ASM contraction, though the PKC isoenzymes involved vary between different
      vasoconstrictors and their actions. Here, we have used confocal microscopy of
      enhanced green fluorescence protein (eGFP)-labeled PKC isoenzymes to visualize
      PKC translocation in primary rat mesenteric ASM cells in response to
      physiological vasoconstrictors, with simultaneous imaging of Ca(2+) signaling.
      Endothelin-1, angiotensin II, and uridine triphosphate all caused translocation
      of each of the PKC isoenzymes alpha, delta, and epsilon; however, the kinetics of
      translocation varied between agonists and PKC isoenzymes. Translocation of eGFP
      PKCalpha mirrored the rise in [Ca(2+)](i), while that of eGFP-PKCdelta or 
      epsilon occurred more slowly. Endothelin-induced translocation of eGFP-PKCepsilon
      was often sustained for several minutes, while responses to angiotensin II were
      always transient. In addition, preventing [Ca(2+)](i) increases using 1,2-bis-(o
      aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetra-(acetoxymethyl) ester
      prevented eGFP-PKCalpha translocation, while eGFP-PKCdelta translocated more
      rapidly. Our results suggest that PKC isoenzyme specificity of vasoconstrictor
      actions occurs downstream of PKC recruitment and demonstrate the varied kinetics
      and complex interplay between Ca(2+) and PKC responses to different
      vasoconstrictors in ASM.

PMID- 18829900
TI  - Decreased lipin 1 beta expression in visceral adipose tissue is associated with
      insulin resistance in polycystic ovary syndrome.
AB  - OBJECTIVE: In polycystic ovary syndrome (PCOS), insulin resistance (IR) appears
      with high prevalence and represents the major cause of cardiometabolic
      complications. Lipin 1beta regulates lipid metabolism and augments insulin
      sensitivity. The impact of lipin 1beta expression in visceral and subcutaneous
      adipose tissue of PCOS patients on IR was studied for the first time. METHODS:
      Eighty-five PCOS patients and 44 controls were enrolled for subcutaneous tissue
      biopsy, of whom 25 patients and 30 controls also underwent visceral adipose
      tissue biopsy. Gene expression of lipin 1beta was measured, together with that of
      peroxisome proliferator-activated receptor gamma, lipoprotein lipase, hormone
      sensitive lipase, adiponectin and glucose transporter 4 in subcutaneous and
      visceral adipose tissue. Markers of obesity, IR and PCOS were also measured.
      RESULTS: In PCOS patients, lipin 1beta expression in both adipose depots was
      lower than in controls: 0.76 (0.67-0.84) vs 1.16 (0.90-1.43) for visceral and
      0.91 (0.73-1.10) vs 1.30 (1.03-1.57) for s.c. depot (both P<10(-4)). The
      difference remained significant after adjustment for body mass index (BMI) and
      also when comparing only lean patients with lean controls. In PCOS patients,
      visceral adipose lipin 1beta expression correlated negatively with homeostasis
      model assessment-IR (r=-0.474, P=0.017), BMI (r=-0.511, P=0.009) and waist
      circumference (r=-0.473, P=0.017), waist circumference remaining significant
      (P=0.027) in multiple regression. Subcutaneous lipin 1beta expression in PCOS
      correlated negatively with BMI, waist circumference and plasma triglycerides, and
      positively with high density lipoprotein-cholesterol. Subcutaneous, but not
      visceral lipin 1beta expression, correlated positively with the studied genes.
      CONCLUSIONS: Lipin 1beta appears to be involved in the pathogenesis of IR in
      PCOS.

PMID- 18829901
TI  - Comparison of autogenous bone graft and endothermic calcium phosphate cement for
      defect augmentation in tibial plateau fractures. A multicenter, prospective,
      randomized study.
AB  - BACKGROUND: Bone graft augmentation is often selected to treat defects associated
      with unstable tibial plateau fractures. This prospective, randomized, multicenter
      study was undertaken to determine the efficacy of bioresorbable calcium phosphate
      cement compared with standard autogenous iliac bone graft in the treatment of
      these osseous defects. METHODS: One hundred and twenty acute, closed, unstable
      tibial plateau fractures (Schatzker types I through VI) in 119 adult patients
      were prospectively enrolled in twelve study sites in North America between 1999
      and 2002. Randomization for the type of grafting of the subarticular defect was
      done at the time of surgery, with use of a 2:1 ratio, to treatment with calcium
      phosphate cement (eighty-two fractures) or autogenous iliac bone graft (thirty
      eight fractures). After open reduction, standard plate-and-screw or screw-only
      fixation was used and then either the cement or the bone graft was placed in the
      defect cavity for subarticular support. Follow-up included standard radiographs,
      evaluated by multiple reviewers to avoid bias, and knee range-of-motion
      assessment at six months to one year or later. RESULTS: The age, weight, height,
      and sex of the patients and the fracture patterns were comparable in the two
      groups, as were union rates and time to union. There was a significantly (p =
      0.009) higher rate of articular subsidence during the three to twelve-month
      follow-up period in the bone graft group. CONCLUSIONS: The bioresorbable calcium
      phosphate cement used in this study appears to be a better choice, at least in
      terms of the prevention of subsidence, than autogenous iliac bone graft for the
      treatment of subarticular defects associated with unstable tibial plateau
      fractures. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions to Authors
      for a complete description of levels of evidence.

PMID- 18829902
TI  - Use of a postoperative lumbar corset after lumbar spinal arthrodesis for
      degenerative conditions of the spine. A prospective randomized trial.
AB  - BACKGROUND: Lumbosacral corsets and braces have been used to treat a variety of
      spinal disorders. Although their use after lumbar arthrodesis for degenerative
      conditions has been reported, there is a lack of evidence on which to base
      guidelines on their use. The purpose of this study was to evaluate the effect of
      a postoperative corset on the outcome of lumbar arthrodesis. METHODS: A
      prospective randomized trial was performed in which patients who wore a
      postoperative lumbar corset for eight weeks full-time after a posterior lumbar
      arthrodesis for a degenerative spinal condition were compared with those who did
      not use a corset after such an operation. Ninety patients were randomized to one
      of the two treatments. A history was recorded and patients were assessed with a
      physical examination, radiographs, and functional outcome questionnaires (the
      Dallas Pain Questionnaire [DPQ] and the Short Form-36 [SF-36]) preoperatively and
      at one year and two years following the surgery. The primary outcome measure of
      the study was the DPQ, a disease-specific patient-derived functional measure of
      the spine, and secondary end points included the SF-36 scores, complications,
      rates of fusion as determined radiographically, and reoperation rates. RESULTS:
      Follow-up analysis was performed for seventy-two patients, thirty-seven
      randomized to the brace (experimental) group and thirty-five randomized to the
      control group. Regardless of the treatment method, the patients had substantial
      improvement in the disease-specific and general health measures by two years
      postoperatively. At two years, there was no difference in the DPQ category scores
      (the primary outcome parameter) of the two treatment groups. There was also no
      difference in the mean SF-36 component scores at two years. Postoperative
      complications occurred in 22% and 23% of patients in the experimental and control
      groups, respectively, and a subsequent lumbar spinal operation was performed in
      19% and 14%, respectively. Seven patients (five in the experimental group and two
      in the control group) with radiographic evidence of nonunion underwent revision
      surgery. CONCLUSIONS: This study does not indicate a significant advantage or
      disadvantage to the use of a postoperative lumbar corset following spinal
      arthrodesis for degenerative conditions of the lumbar spine. LEVEL OF EVIDENCE:
      Therapeutic Level I. See Instructions to Authors for a complete description of
      levels of evidence.

PMID- 18829903
TI  - The reproducibility and repeatability of varus stress radiographs in the
      assessment of isolated fibular collateral ligament and grade-III posterolateral
      knee injuries. An in vitro biomechanical study.
AB  - BACKGROUND: Objective measures to quantitate the amount of lateral compartment
      opening for patients with lateral and posterolateral knee injuries have not been
      well documented. The purpose of the present study was to measure lateral
      compartment opening secondary to applied varus stresses following posterolateral
      corner structure sectioning and to develop radiographic guidelines to quantify
      the amount of lateral compartment gapping seen with these injuries. METHODS: Ten
      nonpaired fresh-frozen cadaver lower extremities were used. Two varus loads, a 12
      Nm moment and a clinician-applied varus stress, were applied to the intact knees
      and after sequential sectioning of the fibular collateral ligament, popliteus
      tendon, popliteofibular ligament, and anterior and posterior cruciate ligaments
      to simulate degrees of posterolateral knee and associated combined cruciate
      ligament injuries. The shortest distance between the most distal subchondral bone
      surface of the lateral femoral condyle and the corresponding lateral tibial
      plateau was measured to quantify lateral compartment opening and was analyzed on
      digital radiographs. Three observers were used to determine interobserver
      reproducibility and intraobserver repeatability. RESULTS: In the intact knee, the
      mean lateral compartment gapping due to a 12-Nm moment and a clinician-applied
      varus stress was 8.9 and 9.7 mm, respectively. Lateral gapping significantly
      increased by 2.1 and 2.7 mm in association with sectioning of the fibular
      collateral ligament and by 3.4 and 4.0 mm in knees with a simulated
      posterolateral corner injury for each respective load-application technique (p <
      0.0001 for all comparisons). Intraobserver repeatability was high, with all
      observers independently obtaining an intraclass correlation coefficient of 0.99,
      whereas the analysis of interobserver reproducibility demonstrated an intraclass
      correlation coefficient of 0.97. CONCLUSIONS: Measurements with use of current
      clinical digital imaging systems can be used to quantify the amount of lateral
      compartment knee opening. Clinicians should suspect an isolated fibular
      collateral ligament injury if opening on clinician-applied varus stress
      radiographs increases by approximately 2.7 mm and a grade-III posterolateral
      corner injury if values increase by approximately 4.0 mm. CLINICAL RELEVANCE:
      Varus stress radiographs appear to provide an objective and reproducible measure
      of lateral compartment gapping that should prove useful for the diagnosis,
      management, and postoperative follow-up of patients with fibular collateral
      ligament and posterolateral knee injuries.

PMID- 18829904
TI  - Surgical treatment of main thoracic scoliosis with thoracoscopic anterior
      instrumentation. a five-year follow-up study.
AB  - BACKGROUND: The surgical outcomes in patients with scoliosis at two years
      following anterior thoracoscopic spinal instrumentation and fusion have been
      reported. The purpose of this study was to evaluate the results at five years.
      METHODS: A consecutive series of forty-one patients with major thoracic scoliosis
      treated with anterior thoracoscopic spinal instrumentation was evaluated at
      regular intervals. Prospectively collected data included patient demographics,
      radiographic measurements, clinical deformity measures, pulmonary function, an
      assessment of intervertebral fusion, and the scores on the Scoliosis Research
      Society (SRS-24) outcomes instrument. Perioperative and postoperative
      complications were recorded. Patient data for the preoperative, two-year, and
      five-year postoperative time points were compared. In addition, a univariate
      analysis compared selected two-year radiographic, pulmonary function, and SRS-24
      data of the study cohort and those of the patients lost to follow-up. RESULTS:
      Twenty-five (61%) of the original forty-one patients had five-year follow-up data
      and were included in the analysis. Between the two-year and five-year follow-up
      visits, no significant changes were observed with regard to the average percent
      correction of the major Cobb angle (56% +/- 11% and 52% +/- 14%, respectively),
      average total lung capacity as a percent of the predicted value (95% +/- 14% and
      91% +/- 10%), and the average total SRS-24 score (4.2 +/- 0.4 and 4.1 +/- 0.7).
      Radiographic evaluation of intervertebral fusion at five years revealed
      convincing evidence of a fusion with remodeling and trabeculae present at 151
      (97%) of the 155 instrumented motion segments. No postoperative infections or
      clinically relevant neurovascular complications were observed. Rod failure
      occurred in three patients, and three patients required a surgical revision with
      posterior spinal instrumentation and fusion. CONCLUSIONS: Thoracoscopic anterior
      instrumentation for main thoracic idiopathic scoliosis results in five-year
      outcomes comparable with those reported previously for open anterior and
      posterior techniques. The radiographic findings, pulmonary function, and clinical
      measures remain stable between the two and five-year follow-up time points.
      Thoracoscopic instrumentation provides a viable alternative to treat spinal
      deformity; however, the risks of pseudarthrosis, hardware failure, and surgical
      revision should be considered along with the advantages of limited muscular
      dissection and improved scar appearance. LEVEL OF EVIDENCE: Therapeutic Level IV.
      See Instructions to Authors for a complete description of levels of evidence.

PMID- 18829905
TI  - Correspondence between perceived disability and objective physical impairment
      after elbow trauma.
AB  - BACKGROUND: Substantial differences between disability and impairment are
      commonplace and puzzling. Subjective (psychosocial) factors may be paramount
      given that pain is a more important determinant of perceived overall arm-specific
      disability than is objective elbow impairment. To further evaluate the
      relationship between impairment and disability, we tested the hypothesis that
      objective loss of elbow motion predicts perceived elbow-related task-specific
      disability better than does pain after elbow trauma. METHODS: One hundred and
      fifty-eight patients were evaluated at a median of twenty-six months after a
      traumatic elbow injury and completed the Disabilities of the Arm, Shoulder and
      Hand (DASH) questionnaire. Predictors of the total DASH score and of the scores
      for individual DASH items that were expected to be related to elbow function were
      evaluated with univariate and multivariate analyses. RESULTS: Motion accounted
      for 35% of the variability in the total DASH score, for 11% to 12% of the
      variability in the responses to questions specific to hand-based activities, and
      for 24% to 33% of the variability in the scores for tasks depending on elbow
      motion. Pain accounted for 41% of the variability in the total DASH score and was
      a better predictor than motion of disability associated with three tasks: opening
      a tight jar (with pain and motion accounting for 24% and 11% of the variability,
      respectively), pushing open a door (25% and 12%, respectively), and placing an
      object overhead (28% and 25%, respectively). None of the multivariate models
      explained more than 53% of the variability in the DASH scores. CONCLUSIONS:
      Objective physical elbow impairment correlated with self-reported disability with
      respect to specific tasks, but a large proportion of disability remains
      unexplained. Further research is needed to better understand the differences
      between objective impairment and perceived disability.

PMID- 18829906
TI  - Averaging different alignment axes improves femoral rotational alignment in
      computer-navigated total knee arthroplasty.
AB  - BACKGROUND: Computer navigation systems generally establish the rotational
      alignment axis of the femoral component on the basis of user-defined anatomic
      landmarks. However, navigation systems can also record knee kinematics and
      average alignment axes established with multiple techniques. We hypothesized that
      establishing femoral rotational alignment with the use of kinematic techniques is
      more accurate and precise (repeatable) than the use of anatomic techniques and
      that establishing femoral rotational alignment by averaging the results of
      different alignment techniques is more accurate and precise than the use of a
      single technique. METHODS: Twelve orthopaedic surgeons used three anatomic and
      two kinematic alignment techniques to establish femoral rotational alignment axes
      in a series of nine cadaver knees. The axes derived with the individual anatomic
      and kinematic techniques as well as the axes derived with six combination
      techniques--i.e., those involving averaging of the alignments established with
      two of the individual techniques--were compared against a reference axis
      established with computed tomography images of each femur. RESULTS: The kinematic
      methods were not more accurate (did not have smaller mean errors) or more precise
      (repeatable) than the anatomic techniques. The combination techniques were
      accurate (five of the six had a mean error of <5 degrees ) and significantly more
      precise than all but one of the single methods. The percentage of measurements
      with <5 degrees of error as compared with the reference epicondylar axis was 37%
      for the individual anatomic techniques, 30% for the individual kinematic
      techniques, and 58% for the combination techniques. CONCLUSIONS: Averaging the
      results of kinematic and anatomic techniques, which is possible with computer
      navigation systems, appears to improve the accuracy of rotational alignment of
      the femoral component. The number of rotational alignment outliers was reduced
      when combination techniques were used; however, they are still a problem and
      continued improvement in methods to accurately establish rotation of the femoral
      component in total knee arthroplasty is needed.

PMID- 18829907
TI  - Patients with workers' compensation claims have worse outcomes after rotator cuff
      repair.
AB  - BACKGROUND: Previous studies have demonstrated varying correlations between
      Workers' Compensation status and the outcome of rotator cuff repair. However,
      none of those studies have formally accounted for potential confounding factors
      with multivariable analysis. We hypothesized that patients with Workers'
      Compensation claims who undergo rotator cuff repair have worse outcomes, even
      after controlling for confounding factors. METHODS: One hundred and twenty-five
      patients (including thirty-nine with Workers' Compensation claims) who underwent
      unilateral primary repair of a chronic rotator cuff tear by a single surgeon were
      studied prospectively and were evaluated one year postoperatively, prior to the
      settlement of any claims. Outcomes were assessed with the Simple Shoulder Test
      (SST); the Disabilities of the Arm, Shoulder and Hand (DASH) index; three visual
      analog scales (shoulder pain, shoulder function, and quality of life); and the
      Short Form-36 (SF-36). RESULTS: Patients in the Workers' Compensation group were
      significantly younger, had greater work demands, and had lower marital rates,
      education levels, and preoperative expectations for the outcome of treatment as
      compared with those in the non-Workers' Compensation group (p = 0.001 to 0.016).
      Preoperatively, patients in the Workers' Compensation group had significantly
      lower scores on the SST, the SF-36 Physical Function scale, and the SF-36 Social
      Function scale (p = 0.01 to 0.038). One year postoperatively, those patients
      reported worse performance on the SST, the DASH, all three visual analog scales,
      and the SF-36 (p = 0.0007 to 0.05) and had worse improvement on the DASH, the
      visual analog scales for shoulder pain and function, and the SF-36 Bodily Pain
      and Role Emotional scales (p = 0.0028 to 0.038). Multivariable analysis
      controlling for age, sex, comorbidities, smoking, marital status, education,
      duration of symptoms, work demands, expectations, and tear size confirmed that
      Workers' Compensation status was an independent predictor of worse DASH scores.
      CONCLUSIONS: Patients with Workers' Compensation claims report worse outcomes,
      even after controlling for confounding factors. The present study provides
      further evidence that the existence of a Workers' Compensation claim portends a
      less robust outcome following rotator cuff repair. LEVEL OF EVIDENCE: Prognostic
      Level I. See Instructions to Authors for a complete description of levels of
      evidence.

PMID- 18829908
TI  - Single-leg-stance (flamingo) radiographs to assess pelvic instability: how much
      motion is normal?
AB  - BACKGROUND: Chronic pelvic instability is a relatively uncommon cause of pelvic
      and low-back pain. Patients present with feelings of instability and mechanical
      symptoms. Static radiographs are often inadequate to detect abnormal relative
      motion between the hemipelves consistent with chronic pelvic instability; dynamic
      views of the pelvis are required. We assessed the amount of physiologic motion
      present at the pubic symphysis in normal adult men and nulliparous and
      multiparous women with alternating-single-leg-stance radiographs. METHODS: Forty
      five asymptomatic adult volunteers (fifteen in each group) were evaluated with a
      standing anteroposterior pelvic radiograph as well as with anteroposterior pelvic
      radiographs made with the subjects assuming both right and left single-leg
      stance. The subjects completed a questionnaire to determine their eligibility for
      participation in the study, and an examination was performed to exclude certain
      physical anomalies that might alter the radiographic findings. RESULTS: The mean
      total translation (and standard deviation) at the pubic symphysis, as measured by
      three blinded observers, was 1.4 +/- 1.0, 1.6 +/- 0.8, and 3.1 +/- 1.5 mm for the
      men, nulliparous women, and multiparous women, respectively. With the numbers
      available, we found no significant difference between the translation in the men
      and that in the nulliparous women (p = 0.63). The multiparous women had
      significantly more translation than did either the nulliparous women (p = 0.002)
      or the men (p = 0.0005). There was a significant positive association between the
      number of pregnancies and the total translation (p < 0.0001). CONCLUSIONS: The
      use of anteroposterior pelvic radiographs made with the subject alternating
      between right and left single-leg stance demonstrated, with high interobserver
      reliability, that multiparous women had a significantly different physiologic
      range of pubic translation as compared with men and nulliparous women. The ranges
      of physiologic motion at the pubic symphysis measured on the single-leg-stance
      radiographs in this study can be used to identify pathologic amounts of motion at
      this site. CLINICAL RELEVANCE: This investigation suggests that up to 5 mm of
      physiologic motion can occur at the pubic symphysis in asymptomatic individuals,
      as demonstrated by alternating-single-leg-stance radiographs.

PMID- 18829909
TI  - Single-leg-stance radiographs in the diagnosis of pelvic instability.
AB  - BACKGROUND: In the nonacute setting, the diagnosis of pelvic instability is
      difficult. Patients who present with pelvic pain may have underlying instability.
      The purpose of the present study was to report the effectiveness of single-leg
      stance radiographs in the diagnosis of pelvic instability in a consecutive series
      of patients presenting with pelvic pain. METHODS: Thirty-eight consecutive
      patients (twenty-four women and fourteen men) ranging in age from eighteen to
      seventy-eight years who presented with pelvic pain and a history of injury
      (twenty-seven), childbirth (seven [four primiparous and three multiparous]), or
      osteopenia (four) were evaluated with a visual analog scale pain score and a
      standard series of radiographs in an attempt to identify pelvic instability. The
      average time from the onset of symptoms to the evaluation was forty-one months
      (range, six weeks to twenty-seven years). Each patient was evaluated with supine
      anteroposterior, inlet, and outlet pelvic radiographs; a standing anteroposterior
      pelvic radiograph; and two single-leg-standing pelvic radiographs (one with the
      patient standing on the left leg and one with the patient standing on the right
      leg). A positive finding was defined as >or=0.5 cm of vertical translation
      measured at the symphyseal bodies between the two single-leg-stance radiographs.
      RESULTS: Of the thirty-eight patients, twenty-five demonstrated pelvic
      instability (average, 1.98 cm; range, 0.5 to 5 cm). With the numbers available,
      the average visual analog scale pain score for the patients with a stable pelvis
      was not significantly different from that for the patients with an unstable
      pelvis (6.4 +/- 2.9 compared with 7.3 +/- 1.9; p = 0.28). CONCLUSIONS: Standing
      anteroposterior and single-leg-stance pelvic radiographs aid in the diagnosis of
      pelvic instability more effectively than do the standard three radiographs of the
      pelvis made in the supine position or a standing anteroposterior radiograph of
      the pelvis alone. Additional studies will be needed to correlate this instability
      with clinical symptoms. LEVEL OF EVIDENCE: Diagnostic Level IV. See Instructions
      to Authors for a complete description of levels of evidence.

PMID- 18829910
TI  - Prophylactic bypass grafting and long-term bracing in the management of
      anterolateral bowing of the tibia and neurofibromatosis-1.
AB  - BACKGROUND: Congenital anterolateral bowing of the tibia is a pre-pseudarthrosis
      stage of congenital pseudarthrosis of the tibia and is associated with a
      substantial risk of fracture and pseudarthrosis. We evaluated the results of
      prophylactic bypass grafting performed in combination with bracing to prevent
      fracture and pseudarthrosis. METHODS: This retrospective series included ten
      patients with pre-pseudarthrosis of the tibia treated, between 1991 and 2002,
      with prophylactic bypass grafting with an allograft fibula placed posteromedially
      in a stress-bearing fashion. The average patient age was 2.3 years at the time of
      diagnosis, 3.6 years at the time of surgery, and ten years at the time of final
      follow-up. The mean duration of follow-up was seventy-eight months. Brace
      protection was recommended at the time of diagnosis and was continued after the
      operation until maturity. Despite the bracing, a low-energy fracture developed
      and partially healed prior to the bypass grafting in one patient. The remaining
      nine patients had no fractures prior to the bypass grafting. At the time of final
      follow-up, the patients were examined clinically and radiographically for the
      presence of a fracture or pseudarthrosis and for residual deformity, including
      malalignment, ankle and knee joint abnormalities, and leg length discrepancy.
      RESULTS: No patient had either a fracture or a pseudarthrosis of the tibia at the
      time of follow-up. All grafts united to the tibia at both ends. Complications
      included an allograft fracture in three patients, which healed in all; allograft
      resorption in one patient; and pseudarthrosis of the ipsilateral host fibula in
      one patient. At the time of final follow-up, a mean of 9 mm (range, 0 to 37 mm)
      of leg length discrepancy was found. A corrective osteotomy was done for four
      patients (three because of ankle valgus and one because of diaphyseal deformity).
      CONCLUSIONS: In this small series of ten patients with congenital anterolateral
      bowing of the tibia treated with bypass strut grafting and long-term bracing,
      there were no cases of pseudarthrosis of the tibia. Distal tibial deformity may
      persist throughout the growth period and require operative correction in patients
      treated with this procedure. LEVEL OF EVIDENCE: Therapeutic Level IV. See
      Instructions to Authors for a complete description of levels of evidence.

PMID- 18829911
TI  - Relationship between hypovascular zones and patterns of ruptures of the
      quadriceps tendon.
AB  - BACKGROUND: Compromised vascularity and hypoxia have been proposed as risks for
      tendon ruptures. The density of vascularity of the quadriceps tendon may explain
      the pattern of ruptures of this muscle-tendon unit. METHODS: Twenty adult human
      cadavers underwent whole-body arterial perfusion with a mixture of lead oxide,
      gelatin, and water through the femoral artery. Thirty-three quadriceps tendons
      were dissected and radiographed, and each angiogram was analyzed with use of
      image statistical software. RESULTS: We consistently identified a hypovascular
      zone located between 1 and 2 cm from the superior pole of the patella. This
      finding correlates with the location of spontaneous ruptures of the quadriceps
      tendon reported in the literature. These findings indicate that the vascular
      supply of the quadriceps tendon is separated into three arcades, or arches, which
      are medial, lateral, and peripatellar. CONCLUSIONS: Hypovascularity may determine
      the site of spontaneous ruptures of the quadriceps tendon. CLINICAL RELEVANCE:
      Understanding the vascular zones of the quadriceps tendon may facilitate the use
      of nonoperative as well as operative treatments to increase the vascularity of
      the tendon. An understanding of the vascular arcades may facilitate and enhance
      healing following reparative and reconstructive surgery on the tendon.

PMID- 18829912
TI  - Low incidence of anti-osteoporosis treatment after hip fracture.
AB  - BACKGROUND: Following hip fracture, pharmacologic treatment can reduce the rate
      of subsequent fragility fractures. The objective of the present study was to
      assess the proportion of patients who are managed with bisphosphonates or
      selective estrogen-receptor modulators after hip fracture and to evaluate, among
      those managed with alendronate, the twelve-month compliance and persistence with
      treatment. METHODS: Data were gathered from health insurance companies and were
      collected by AIM (Agence Intermutualiste) for the Belgian National Social
      Security Institute (INAMI). We selected all postmenopausal women who had been
      hospitalized for a hip fracture between April 2001 and June 2004 and had not been
      previously managed with bisphosphonates. Patients who had received alendronate
      treatment after the hip fracture were categorized according to their formulation
      use during the follow-up study (daily, weekly, daily followed by weekly, or
      weekly followed by weekly). Compliance at twelve months was quantified with use
      of the medication possession ratio (i.e., the number of days of alendronate
      supplied during the first year of treatment, divided by 365). Persistence with
      prescribed treatment was calculated as the number of days from the initial
      prescription to a lapse of more than five weeks after completion of the previous
      prescription refill. The cumulative treatment persistence rate was determined
      with use of Kaplan-Meier survival curves. RESULTS: A total of 23,146 patients who
      had sustained a hip fracture were identified. Of these patients, 6% received
      treatment during the study period: 4.6% received alendronate, 0.7% received
      risedronate, and 0.7% received raloxifene. Bisphosphonate treatment was dispensed
      to 2.6% and 3.6% of the patients within six months and one year after the
      occurrence of the hip fracture, respectively. Among women who received
      alendronate daily (n = 124) or weekly (n = 182) and were followed for at least
      one year after the hip fracture, the twelve-month mean medication possession
      ratio was 67% (65.9% in the daily group and 67.7% in the weekly group). The
      analysis of persistence with treatment included a total of 726 patients (142 in
      the daily group, 261 in the weekly group, and 323 in the switch group). At twelve
      months, the rate of persistence was 41% and the median duration of persistence
      was 40.3 weeks. CONCLUSIONS: The vast majority of patients who experience a hip
      fracture do not take anti-osteoporotic therapy after the fracture. Furthermore,
      among patients who begin alendronate treatment after the fracture, the adherence
      to treatment decreases over time and remains suboptimal.

PMID- 18829913
TI  - Surgical treatment of calcaneal deformity in a select group of patients with
      myelomeningocele.
AB  - BACKGROUND: The surgical treatment of calcaneal deformity in patients with
      myelomeningocele has not been uniformly successful in correcting the deformity
      and preventing recurrence. The purpose of the present study was to examine the
      results of posterior transfer of the anterior tibial tendon with concurrent
      procedures in an attempt to balance the muscular forces on the foot and ankle and
      to obtain a plantigrade foot. We investigated whether surgery improved pressure
      distribution over the plantar surface of the foot and whether concurrent abnormal
      movements observed at the knee, hip, and pelvis influenced the surgical outcome.
      METHODS: Thirty-one feet in eighteen patients who were able to walk were included
      in the study. The mean age at the time of surgery was seven years and four
      months, and the mean duration of follow-up was forty-seven months. Eight patients
      were classified as having an L5-level myelomeningocele, and ten patients were
      classified as having a sacral level myelomeningocele. A tibialis anterior tendon
      transfer was performed in all patients, and accompanying osseous deformities were
      also corrected in twelve feet. Measurements on plain radiographs, the results of
      gait analyses, and dynamic foot pressures that were determined before surgery and
      at the time of the final follow-up were compared. RESULTS: No recurrence or
      worsening of the deformity was observed in any of the patients, and no other
      types of foot deformity developed after surgery. Postoperative kinematic studies
      showed a significant (p < 0.0001) increase in peak plantar flexion and a
      significant decrease in peak dorsiflexion force of the ankle in the stance phase
      of gait. Peak pressures under the forefoot and midfoot were increased after
      surgery, and the relative amount of weight-bearing on the heel as compared with
      the forefoot was shifted toward more equal weight-bearing. However, less
      improvement in foot-pressure distribution was observed in patients with increased
      pelvic rotation before surgery. Those patients also had decreased knee extension
      in stance phase and increased hip abduction and pelvic obliquity both before and
      after surgery in comparison with patients who had normal pelvic rotation.
      CONCLUSIONS: Appropriately combined corrective surgical procedures for the
      treatment of calcaneal deformity in patients with myelomeningocele can
      effectively reduce the pressure placed on the calcaneus, increase pressures in
      the forefoot and midfoot, and prevent recurrence of the calcaneal deformity.
      However, in the presence of excessive pelvic movement in the coronal and
      transverse planes and decreased knee extension in stance phase, adequate
      improvement in pressure distribution over the plantar surface of the foot is not
      likely to occur after this type of foot surgery. LEVEL OF EVIDENCE: Therapeutic
      Level IV. See Instructions to Authors for a complete description of levels of
      evidence.

PMID- 18829914
TI  - Total hip arthroplasty for primary osteoarthritis in patients fifty-five years of
      age or older. An analysis of the Finnish arthroplasty registry.
AB  - BACKGROUND: According to the long-term results obtained from the Scandinavian
      arthroplasty registries, cemented total hip replacement has been the treatment of
      choice for osteoarthritis of the hip in elderly patients. The aim of the present
      study was to analyze population-based survival rates of the cemented and
      cementless total hip replacements performed for primary osteoarthritis in
      patients fifty-five years of age or older in Finland. METHODS: From 1980 to 2004,
      a total of 50,968 primary total hip replacements that met our criteria were
      entered in the Finnish Arthroplasty Registry. The success rate of different
      implant groups was analyzed. The implants included were classified in one of the
      following four groups: implants with a cementless, straight, proximally
      circumferentially porous-coated stem and a modular, porous-coated press-fit cup
      (cementless group 1); implants with a cementless, anatomic, proximally
      circumferentially porous-coated and/or hydroxyapatite-coated stem with a modular,
      porous-coated and/or hydroxyapatite-coated press-fit cup (cementless group 2); a
      hybrid total hip replacement consisting of a cemented stem combined with a
      modular, press-fit cup (the hybrid group); and a cemented loaded-taper or
      composite-beam stem combined with an all-polyethylene cup (the cemented group).
      RESULTS: Cementless total hip replacements, as well as cementless stems and cups
      analyzed separately, had a significantly reduced risk of revision for aseptic
      loosening compared with cemented hip replacements (p < 0.001). When revision for
      any reason was the end point in survival analyses, however, there were no
      significant differences among the groups. In patients between the ages of fifty
      five and sixty-four years, the fifteen-year survival rates of the two cementless
      groups (78% and 80%) were higher than that of the cemented group (71%) with
      revision for aseptic loosening as the end point. In patients who were sixty-five
      to seventy-four years old, the fifteen-year survival rate of the implants in
      cementless group 1 was 94%, while cemented total hip replacements had an 85%
      survival rate. In patients who were seventy-five years old or more, no
      significant differences were detected among the total hip replacement groups; all
      of them had survivorship of >90% at ten years. CONCLUSIONS: In patients who were
      fifty-five years of age or older, the long-term survival of cementless total hip
      replacements was comparable with that of cemented replacements. In patients who
      were fifty-five to seventy-four years old, straight porous-coated cementless
      stems had better long-term survival than the cemented stems. In patients who were
      seventy-five years of age and older, there were no significant differences in the
      results. Multiple wear-related revisions of the cementless cups in the present
      study indicate that excessive polyethylene wear was a major clinical problem with
      modular cementless cups in all age groups. LEVEL OF EVIDENCE: Therapeutic Level
      III. See Instructions to Authors for a complete description of levels of
      evidence.

PMID- 18829915
TI  - The early effects of tendon transfers and open capsulorrhaphy on glenohumeral
      deformity in brachial plexus birth palsy.
AB  - BACKGROUND: Persistent muscle imbalance and soft-tissue contractures can lead to
      progressive glenohumeral joint dysplasia in patients with brachial plexus birth
      palsy. The objective of the present investigation was to determine the effects of
      tendon transfers and open glenohumeral reduction on shoulder function and
      dysplasia in patients with preexisting joint deformity secondary to brachial
      plexus birth palsy. METHODS: Twenty-three patients with preexisting glenohumeral
      deformity underwent latissimus dorsi and teres major tendon transfers to the
      rotator cuff with concomitant musculotendinous lengthening of the pectoralis
      major and/or subscapularis and open glenohumeral joint reduction for the
      treatment of internal rotation contracture and external rotation weakness.
      Shoulder function was assessed with use of the modified Mallet classification
      system and the Active Movement Scale. Glenoid version and humeral head
      subluxation were quantified radiographically, and glenohumeral deformity was
      appropriately graded. The mean duration of clinical and radiographic follow-up
      was thirty-one and twenty-five months, respectively. RESULTS: Clinically, all
      patients demonstrated improved global shoulder function, with the mean aggregate
      Mallet score improving from 10 points preoperatively to 18 points postoperatively
      (p < 0.01). The mean modified Mallet score for external rotation improved from 2
      to 4 (p < 0.01). Similarly, the mean Active Movement Scale score for external
      rotation improved from 3 to 6 (p < 0.01). The mean Mallet hand-to-spine score
      improved from 1 to 2 (p < 0.01). The mean Active Movement Scale score for
      internal rotation remained constant at 6. Radiographically, the mean glenoid
      version improved from -39 degrees preoperatively to -18 degrees postoperatively
      (p < 0.01). The mean percentage of the humeral head anterior to the middle of the
      glenoid similarly improved from 13% to 38% (p < 0.01). The mean glenohumeral
      deformity score improved from 3 to 2 (p < 0.01). Nineteen (83%) of the twenty
      three patients demonstrated glenohumeral remodeling; one patient had progressive
      worsening of glenohumeral deformity. CONCLUSIONS: Tendon transfers to the rotator
      cuff, combined with musculotendinous lengthenings and open reduction of the
      glenohumeral joint, improve global shoulder function and lead to glenohumeral
      joint remodeling in the majority of selected patients with mild-to-moderate
      preexisting glenohumeral dysplasia secondary to brachial plexus birth palsy.
      Future study of the long-term outcomes of these procedures will help to clarify
      the ultimate effect on glenohumeral joint function. LEVEL OF EVIDENCE:
      Therapeutic Level IV. See Instructions to Authors for a complete description of
      levels of evidence.

PMID- 18829916
TI  - Total shoulder arthroplasty with a metal-backed, bone-ingrowth glenoid component.
      Medium to long-term results.
AB  - BACKGROUND: Loosening of a cemented glenoid component is an important cause of
      failure in shoulder arthroplasty. This study was developed to examine the outcome
      of patients managed with a metal-backed, bone-ingrowth glenoid component as an
      alternative to a cemented component. METHODS: The study group included eighty
      three total shoulder arthroplasties with a metal-backed, bone-ingrowth glenoid
      component performed between 1989 and 1994. Seventy-four shoulders had a diagnosis
      of primary osteoarthritis, and nine shoulders had other diagnoses. All patients
      were followed radiographically and clinically for a minimum of two years or until
      the time of revision surgery. Kaplan-Meier survival estimates were performed with
      revision and/or radiographic failure as the end points. RESULTS: The mean
      clinical follow-up was 9.5 years, and the mean radiographic follow-up was 7.1
      years. Pain ratings (on a scale of 1 to 5) decreased from a mean of 4.7
      preoperatively to 2.0 postoperatively. The mean range of motion in active
      elevation increased from 102 degrees preoperatively to 135 degrees
      postoperatively; the mean external rotation increased from 27 degrees to 56
      degrees . Glenohumeral joint instability developed in fourteen shoulders.
      Radiographic changes consistent with glenoid component loosening were present in
      thirty-three shoulders. Polyethylene wear with metal wear of the glenoid
      component was noted in twenty-one shoulders, and humeral component loosening was
      seen in fifteen shoulders. Revision procedures were performed in twenty-six
      shoulders. There were no identifiable patient, disease, or surgical
      characteristics associated with failure, either clinically or radiographically.
      The five-year survival estimate free of revision or radiographic failure was
      79.9% (95% confidence interval, 71.6% to 89.3%), and the ten-year survival
      estimate was 51.9% (95% confidence interval, 41.0% to 65.8%). CONCLUSIONS: The
      high rate of failure of total shoulder arthroplasties performed with this metal
      backed, bone-ingrowth glenoid component raises concerns as to its use, and
      perhaps the use of other types of metal-backed components, in shoulder
      arthroplasty, other than for special situations. LEVEL OF EVIDENCE: Therapeutic
      Level IV. See Instructions to Authors for a complete description of levels of
      evidence.

PMID- 18829918
TI  - Management of acute distal humeral fractures in patients with rheumatoid
      arthritis. A case series.
AB  - BACKGROUND: The best surgical treatment for a patient with rheumatoid arthritis
      and an acute distal humeral fracture is not well established. Because of the
      distorted anatomy of the arthritic elbow joint and the adjacent osteoporotic
      bone, total elbow arthroplasty may be favored over open reduction and internal
      fixation in these patients. We retrospectively analyzed a series of patients with
      rheumatoid arthritis in whom an acute distal humeral fracture had been treated
      with either open reduction and internal fixation or total elbow arthroplasty; our
      purpose was to evaluate their outcomes and to identify any influence of age,
      fracture type, or the extent of the rheumatoid involvement of the elbow joint on
      the choice of procedure. METHODS: Between 1982 and 2002, an acute distal humeral
      fracture was treated surgically in sixteen elbows in fourteen patients with
      rheumatoid arthritis, and the results were retrospectively reviewed at a minimum
      of twenty-four months postoperatively. Six elbows were treated with open
      reduction and internal fixation (Group 1) and ten elbows, with primary total
      elbow arthroplasty (Group 2). Postoperatively, the elbows were examined with
      standard radiographs, and the clinical outcome was assessed with the Mayo Elbow
      Performance Score (MEPS). RESULTS: Six patients (six elbows) died before the time
      of the study, but they had been followed for more than twenty-four months and
      therefore were included in the series. The eight patients (ten elbows) who were
      still alive were examined. The mean duration of follow-up was forty-nine months
      in Group 1 and sixty-six months in Group 2. The MEPS averaged 93 points in Group
      1 and 96 points in Group 2. Radiographically, all fractures had healed
      uneventfully in Group 1 and no prosthesis was loose in Group 2. We could not
      identify any difference between Groups 1 and 2 with respect to patient age,
      fracture type, or extent of the rheumatoid arthritis. CONCLUSIONS: Distal humeral
      fractures in patients with rheumatoid arthritis can be treated successfully with
      immediate open reduction and internal fixation or with total elbow arthroplasty.
      Our data suggest that open reduction and internal fixation can be successful when
      there is mild arthritic involvement. We favor total elbow arthroplasty for
      patients with severe articular involvement. LEVEL OF EVIDENCE: Therapeutic Level
      IV. See Instructions to Authors for a complete description of levels of evidence.

PMID- 18829917
TI  - Enhancement of periprosthetic bone quality with topical hydroxyapatite
      bisphosphonate composite.
AB  - BACKGROUND: Implant loosening is associated with inflammatory bone loss induced
      by ultra-high molecular weight polyethylene wear debris. We hypothesized that a
      hydroxyapatite-bisphosphonate composite improves periprosthetic bone quality and
      osseous integration of an intramedullary implant even in the presence of ultra
      high molecular weight polyethylene particles in an experimental rat femur model.
      METHODS: A preliminary in vitro study determined the optimal concentration of
      zoledronate (50 microM) that would maximally decrease osteoclasts without harming
      osteoblasts. Hydroxyapatite-coated intramedullary nails were implanted
      bilaterally in the femora of sixteen rats (the control group), and hydroxyapatite
      zoledronate-coated nails were implanted bilaterally in the femora of sixteen rats
      (the experimental group). Ultra-high molecular weight polyethylene particles were
      introduced into the femoral canal before implantation. Eight rats from each group
      were killed at six weeks, and the remaining rats were killed at six months.
      Periprosthetic bone mass was analyzed by dual x-ray absorptiometry and
      microcomputed tomography. Osseous integration was examined by biomechanical
      testing of pullout strength. RESULTS: The mean bone area (and standard deviation)
      in the periprosthetic bone region was significantly greater (p < 0.0001) in the
      hydroxyapatite-zoledronate group (2.388 +/- 0.960 mm2) than in the control group
      (0.933 +/- 0.571 mm2). This difference was larger in the six-week group than in
      the six-month group (p = 0.03). The average peak pullout force for the treated
      femora (241.0 +/- 95.1 N) was significantly greater (p < 0.0001) than that for
      the controls (55.6 +/- 49.0 N). This difference was similar in the six-week and
      six-month groups. The energy required for nail pullout was significantly greater
      (p < 0.0001) for the treated femora (521.6 +/- 293.8 N-mm) than for the controls
      (142.2 +/- 152.1 N-mm). This difference in energy to pullout was similar in the
      six-week and six-month groups. Regression analysis demonstrated a high
      correlation between periprosthetic bone mass and peak pullout force for both the
      six-week (r = 0.766, p = 0.0005) and six-month (r = 0.838, p < 0.0001) groups.
      CONCLUSIONS: Surface modification of implants with hydroxyapatite-zoledronate
      improves periprosthetic bone quality and osseous integration. CLINICAL RELEVANCE:
      Hydroxyapatite-based site-specific delivery of bisphosphonates may be one way of
      reducing ultra-high molecular weight polyethylene wear particle-induced
      periprosthetic osteolysis and implant loosening.

PMID- 18829919
TI  - rhBMP-12 accelerates healing of rotator cuff repairs in a sheep model.
AB  - BACKGROUND: The success rate of rotator cuff repairs is variable. This study was
      performed to evaluate the ability of recombinant human bone morphogenetic protein
      12 (rhBMP-12), administered in several carriers, to accelerate healing in a sheep
      model of rotator cuff repair. METHODS: Local retention of tracer amounts of
      radiolabeled rhBMP-12, added to non-radiolabeled rhBMP-12 delivered in buffer,
      hyaluronan paste or sponges, or Type-I or Type-I/III collagen sponges was first
      evaluated with use of gamma scintigraphy in a pilot study of a rat intramuscular
      implant model. The rhBMP-12/paste and sponge combinations were then evaluated in
      eight sheep each with unilateral complete detachment and subsequent double-row
      reattachment of the infraspinatus tendon to the proximal part of the humerus.
      Contralateral, normal shoulders from sixteen sheep and shoulders in which a
      repair had been done without administration of rhBMP-12 in fourteen sheep were
      also evaluated. The rhBMP-12/Type-I and Type-I/III collagen sponge combinations
      were each evaluated in eight additional sheep on the basis of superior efficacy.
      The Type-I/III collagen sponge alone was evaluated in ten sheep to examine the
      effect of a collagen carrier. Ultrasound imaging was performed at four and eight
      weeks. Radiographic evaluation, mechanical testing, and biochemical evaluation
      were performed at eight weeks. Histological evaluation was performed on specimens
      from the sites of selected repairs following mechanical testing. RESULTS: The
      sponge carriers had longer local retention of rhBMP-12 than did the buffer or
      paste carriers in the rat models. All of the sheep shoulder-repair groups
      demonstrated ultrasound evidence of a gap between the tendon and the humeral
      insertion. The gap length and the cross-sectional area of the repair tissue
      decreased with time. The mechanical properties of the repairs treated with rhBMP
      12 and hyaluronan paste were similar to those of the untreated repairs. The
      maximum loads for the rhBMP-12/hyaluronan sponge and rhBMP-12/collagen sponge
      treated repairs were 2.1 and 2.7 times greater, respectively, than the loads for
      the untreated repairs and were 33% and 42% of the value for the normal tendon at
      eight weeks. The maximum loads for the repairs treated with rhBMP-12 and a Type-I
      or Type-I/III collagen sponge were 2.1 times greater than those for the repairs
      treated with the Type-I/III collagen sponge alone. Changes in maximum stiffness
      followed a similar pattern. Histological evaluation demonstrated accelerated
      healing of the rhBMP-12-treated repairs compared with the untreated repairs. Bone
      formation was observed in all repairs, and biochemical measurements were not
      equivalent to those of normal tendon at eight weeks. CONCLUSIONS: Delivery of
      rhBMP-12 in a collagen or hyaluronan sponge resulted in accelerated healing of
      acute full-thickness rotator cuff repairs in a sheep model. CLINICAL RELEVANCE:
      Delivery of rhBMP-12 in several sponge carriers has the potential to accelerate
      healing of rotator cuff repairs. Accelerated repair may allow shorter
      rehabilitation and an earlier return to occupational and recreational activities.

PMID- 18829920
TI  - Thrombophilia, hypofibrinolysis, the eNOS T-786C polymorphism, and multifocal
      osteonecrosis.
AB  - BACKGROUND: We examined the hypothesis that thrombophilia, hypofibrinolysis, and
      the endothelial nitric oxide synthase (eNOS) T-786C polymorphism are common,
      potentially treatable, and similar pathophysiologic causes of multifocal (three
      sites or more) and unifocal (single-site) osteonecrosis. METHODS: We
      prospectively evaluated twenty-six consecutively referred adults with multifocal
      osteonecrosis, who included thirteen with idiopathic multifocal osteonecrosis and
      thirteen with secondary multifocal osteonecrosis (resulting from steroid therapy
      in ten and alcoholism in three). We compared these patients with race, sex, and
      age-matched normal control subjects and with patients with idiopathic unifocal
      and secondary unifocal osteonecrosis, respectively. Using polymerase chain
      reaction and serologic measures, we studied thrombophilic and hypofibrinolytic
      mutations and the eNOS T-786C polymorphism. RESULTS: The total number of
      polymerase chain reaction and serologic thrombophilic-hypofibrinolytic
      abnormalities and the eNOS T-786C polymorphism did not differ between patients
      with idiopathic (p > 0.5) or secondary (p > 0.5) multifocal and unifocal
      osteonecrosis. The frequency of low free protein-S levels (<66%) in patients with
      secondary multifocal osteonecrosis (four of eleven patients) was higher than that
      in the control subjects (one of fifty-nine) (risk ratio = 21.5; 95% confidence
      interval, 2.6 to 174; p = 0.0016, Benjamini-Hochberg adjusted p [Bp] = 0.004).
      Factor-V Leiden heterozygosity was present in two of thirteen patients with
      secondary multifocal osteonecrosis compared with none of sixty-four control
      subjects (p = 0.027, Bp = 0.008). For eleven patients with secondary multifocal
      osteonecrosis, the eNOS T-786C polymorphism was present in nine of twenty-two
      alleles compared with eight of forty-four alleles in twenty-two normal control
      subjects (risk ratio = 2.3; 95% confidence interval, 1.0 to 5.0; p = 0.047, Bp =
      0.016). The frequency of homocystinemia (>13.5 mumol/L) was higher in patients
      with idiopathic multifocal osteonecrosis (two of thirteen patients) than in
      normal controls (none of fifty-one) (p = 0.039, Bp = 0.004). A high level of
      factor VIII (>150%) was seen in four of eight patients with idiopathic multifocal
      osteonecrosis and in seven of forty-eight normal controls (risk ratio = 3.4; 95%
      confidence interval, 1.3 to 9.1; p = 0.04, Bp = 0.008). The eNOS T-786C mutant
      allele was present in seven of twelve alleles in the six patients with idiopathic
      multifocal osteonecrosis who were tested, compared with twenty-five of 108
      alleles in fifty-four control subjects (risk ratio = 2.5; 95% confidence
      interval, 1.4 to 4.5; p = 0.015, Bp = 0.008). CONCLUSIONS: Limited by the small
      numbers of patients with multifocal osteonecrosis, this exploratory study
      suggested that thrombophilia was associated with both idiopathic multifocal
      osteonecrosis and secondary multifocal osteonecrosis, as was the eNOS T-786C
      polymorphism. Multifocal and unifocal osteonecrosis are similarly associated with
      thrombophilia, hypofibrinolysis, and the eNOS T-786C polymorphism, which are
      potentially treatable pathophysiologic conditions, requiring further study.

PMID- 18829921
TI  - Chronic failure of a lumbar total disc replacement with osteolysis. Report of a
      case with nineteen-year follow-up.

PMID- 18829922
TI  - Pseudoaneurysm of the anterior tibial artery after ankle arthroscopy treated with
      ultrasound-guided compression therapy. A case report.

PMID- 18829923
TI  - Nonresectable multiple lung metastases of high-grade osteosarcoma of the humerus:
      stable after twelve years. A case report.

PMID- 18829924
TI  - Athletic activity after total joint arthroplasty.
AB  - Demand for total joint arthroplasty is projected to increase in the first three
      decades of the twenty-first century. With increasing frequency, patients who have
      a hip or knee replacement expect to, and choose to, participate in athletics
      following rehabilitation. In general, patients who have had a hip or knee
      replacement decrease their participation in, and intensity of, athletic activity
      following the total joint arthroplasty. The orthopaedic literature on athletic
      activity after total joint arthroplasty is limited to small retrospective studies
      with short-term follow-up. Expert opinion regarding appropriate athletic activity
      after total joint arthroplasty is available from the Hip Society and the Knee
      Society. When patients who have undergone joint replacements choose to
      participate in athletic activity, orthopaedic surgeons should provide information
      with which to evaluate the risk of sports activity and recommend appropriate
      athletic activity.

PMID- 18829925
TI  - Treatment of femoral neck fractures in young adults.

PMID- 18829926
TI  - AOA symposium. Hip disease in the young adult: current concepts of etiology and
      surgical treatment.

PMID- 18829927
TI  - Medicare part B: physician participation options.

PMID- 18829929
TI  - What's new in orthopaedic rehabilitation.

PMID- 18829928
TI  - Design and implementation of a system-based course in musculoskeletal medicine
      for medical students.
AB  - BACKGROUND: The amount of time devoted to musculoskeletal medicine in the typical
      undergraduate curriculum is disproportionately low compared with the frequency of
      musculoskeletal complaints that occur in a general practice. Consequently,
      whether because of the quantity or quality of the education, the competence level
      of graduating physicians regarding musculoskeletal problems is inadequate. Our
      purposes were to design a self-contained, system-based course in musculoskeletal
      medicine for medical students in the preclinical years and to measure the level
      of competence achieved by a class of first-year medical students who took the
      course. METHODS: The course was formulated by faculty from the departments of
      orthopaedic surgery, anatomy, and rheumatology and included elements of both
      objectives-based and problem-centered curricular models. The clinical lectures
      were preceded by pertinent anatomy lectures and dissections to provide a context
      for the clinical information. The lectures on basic science were designed to
      rationalize and explicate clinical practices. Small-group activities were
      incorporated to permit engagement of the students in critical thinking and
      problem-solving. A general musculoskeletal physical examination was taught in two
      two-hour-long small-group sessions with the orthopaedic residents serving as
      instructors. Cognitive competency was evaluated with use of comprehensive anatomy
      laboratory and written examinations, the latter of which included a validated
      basic competency examination in musculoskeletal medicine. Process-based skills
      were evaluated in the small-group meetings and in a timed, mock patient encounter
      in which each student's ability to perform the general musculoskeletal physical
      examination was assessed. RESULTS: The course lasted six weeks and consisted of
      forty-four lecture hours, seventeen hours of small-group meetings, and twenty
      eight hours of anatomy laboratory. The average student score on the basic
      competency examination was 77.8%, compared with 59.6% for a historical comparison
      group (p < 0.05). Each student demonstrated the ability to adequately perform a
      general musculoskeletal physical examination in twenty minutes. The survey of
      student opinion after the course indicated a high level of student satisfaction.
      CONCLUSIONS: The main features of the course were: (1) an emphasis on both
      cognitive and process-based knowledge; (2) more contact hours and broader content
      than in previously described courses in musculoskeletal medicine; (3) the use of
      small groups to focus on problem-solving and physical examination competencies;
      (4) basic-science content directly related to clinical goals. These features
      might be used at other institutions that employ a system-based curriculum for the
      preclinical years to help improve competence in musculoskeletal medicine.

PMID- 18829930
TI  - Hallux valgus and first ray mobility. Surgical technique.
AB  - BACKGROUND: There have been few prospective studies that have documented the
      outcome of surgical treatment of hallux valgus deformities. The purpose of this
      investigation was to evaluate the effect of operative treatment of hallux valgus
      with use of a proximal crescentic osteotomy and distal soft-tissue repair on the
      first metatarsophalangeal joint. METHODS: All adult patients in whom moderate or
      severe subluxated hallux valgus deformities had been treated with surgical repair
      between September 1999 and May 2002 were initially enrolled in the study. Those
      who had a hallux valgus deformity treated with a proximal crescentic osteotomy
      and distal soft-tissue reconstruction (and optional Akin phalangeal osteotomy)
      were then invited to return for a follow-up evaluation at a minimum of two years
      after surgery. Outcomes were assessed by a comparison of preoperative and
      postoperative pain and American Orthopaedic Foot and Ankle Society scores;
      objective measurements included ankle range of motion, Harris mat imprints,
      mobility of the first ray (assessed with use of a validated calibrated device),
      and radiographic angular measurements. RESULTS: Of the 108 patients (127 feet),
      five patients (five feet) were unavailable for follow-up, leaving 103 patients
      (122 feet) with a diagnosis of moderate or severe primary hallux valgus who
      returned for the final evaluation. The mean duration of follow-up after the
      surgical repair was twenty-seven months. The mean pain score improved from 6.5
      points preoperatively to 1.1 points following surgery. The mean American
      Orthopaedic Foot and Ankle Society score improved from 57 points preoperatively
      to 91 points postoperatively. One hundred and fourteen feet (93%) were rated as
      having good or excellent results following surgery. Twenty-three feet
      demonstrated increased mobility of the first ray prior to surgery, and only two
      feet did so following the bunion surgery. The mean hallux valgus angle diminished
      from 30 degrees preoperatively to 10 degrees postoperatively, and the mean first
      second intermetatarsal angle decreased from 14.5 degrees preoperatively to 5.4
      degrees postoperatively. Plantar gapping at the first metatarsocuneiform joint
      was observed in the preoperative weight-bearing lateral radiographs of twenty
      eight (23%) of 122 feet, and it had resolved in one-third (nine) of them after
      hallux valgus correction. Complications included recurrence in six feet. First
      ray mobility was not associated with plantar gapping. There was a correlation
      between preoperative mobility of the first ray and the preoperative hallux valgus
      (r = 0.178) and the first-second intermetatarsal angles (r = 0.181). No
      correlation was detected between restricted ankle dorsiflexion and the magnitude
      of the preoperative hallux valgus deformity, the postoperative hallux valgus
      deformity, or the magnitude of hallux valgus correction. CONCLUSIONS: A proximal
      crescentic osteotomy of the first metatarsal combined with distal soft-tissue
      realignment should be considered in the surgical management of moderate and
      severe subluxated hallux valgus deformities. First ray mobility was routinely
      reduced to a normal level without the need for an arthrodesis of the
      metatarsocuneiform joint. Plantar gapping is not a reliable radiographic
      indication of hypermobility of the first ray in the sagittal plane.

PMID- 18829931
TI  - Comparison of arthrodesis and metallic hemiarthroplasty of the hallux
      metatarsophalangeal joint. Surgical technique.
AB  - BACKGROUND: Currently, arthrodesis is the most commonly performed surgical
      procedure for the treatment of severe arthritis of the first metatarsophalangeal
      joint. The objective of this study was to compare the long-term clinical and
      radiographic outcomes of a metallic hemiarthroplasty with those of arthrodesis
      for the treatment of this condition. METHODS: A series of patients with
      osteoarthritis of the first metatarsophalangeal joint were treated with either a
      metallic hemiarthroplasty or an arthrodesis between 1999 and 2005. Postoperative
      satisfaction and function were graded with use of the American Orthopaedic Foot
      and Ankle Society Hallux Metatarsophalangeal Interphalangeal (AOFAS-HMI) scoring
      system, and pain was scored with use of a visual analogue scale. RESULTS: Twenty
      one hemiarthroplasties and twenty-seven arthrodeses were performed in forty-six
      patients. Five (24%) of the hemiarthroplasties failed; one of them was revised,
      and four were converted to an arthrodesis. Eight of the feet in which the
      hemiprosthesis had survived had evidence of plantar cutout of the prosthetic stem
      on the final follow-up radiographs. At the time of final follow-up (at a mean of
      79.4 months), the satisfaction ratings in the hemiarthroplasty group were good or
      excellent for twelve feet, fair for two, and poor or a failure for seven. The
      mean pain score was 2.4 of 10. All twenty-seven of the arthrodeses achieved
      fusion, and no revisions were required. At the time of final follow-up (at a mean
      of thirty months), the satisfaction ratings in this group were good or excellent
      for twenty-two feet, fair for four, and poor for one. The mean pain score was 0.7
      of 10. Two patients required hardware removal, which was performed as an office
      procedure with the use of local anesthesia. The AOFAS-HMI and visual analogue
      pain scores and satisfaction were significantly better in the arthrodesis group.
      CONCLUSIONS: Arthrodesis is more predictable than a metallic hemiarthroplasty for
      alleviating symptoms and restoring function in patients with severe
      osteoarthritis of the first metatarsophalangeal joint.

PMID- 18829932
TI  - Distal tibial reconstruction with use of a circular external fixator and an
      intramedullary nail. Surgical technique.
AB  - BACKGROUND: Distal tibial reconstruction with use of an external fixator when
      there is bone loss, limb-length discrepancy, and/or ankle instability is
      associated with many problems. The technique of limb-lengthening, ankle
      arthrodesis, and segmental transfer over an intramedullary nail has been
      introduced to overcome these problems. The present study investigates this
      combined technique. METHODS: Between 2002 and 2005, six patients, who ranged from
      seventeen to seventy years old, underwent distal tibial reconstruction and ankle
      arthrodesis with use of a circular external fixator and an intramedullary nail to
      treat a distal tibial defect following resection for chronic osteomyelitis or
      tumor or to treat a limb-length discrepancy combined with ankle instability.
      Functional and radiographic results were evaluated, with use of the criteria
      described by Paley et al., at an average follow-up of thirty-four months.
      RESULTS: The mean size of the bone defect in three patients was 5.3 cm (2, 7, and
      7 cm), and the mean amount of the limb-shortening in four patients was 5.25 cm
      (range, 4 to 6 cm). The mean external fixation time was 3.5 months, and the mean
      external fixator index was 0.57 mo/cm. There was no recurrence of infection in
      the two patients with osteomyelitis. All six patients had excellent bone results,
      and the functional results were excellent for two patients and good for four
      patients. There were four complications, three of which were categorized,
      according to Paley, as a problem (a difficulty that occurs during lengthening and
      is resolved without operative intervention) and one that was categorized as an
      obstacle (a difficulty that occurs during lengthening and needs operative
      treatment). CONCLUSIONS: The combined technique is an improvement over the
      classic external fixation techniques of distal tibial reconstruction with ankle
      arthrodesis. It reduces the duration of external fixation, thus increasing
      patient acceptance, and it is associated with a low complication rate
      facilitating more rapid rehabilitation.

PMID- 18829933
TI  - Lateral unicompartmental knee arthroplasty through a medial approach. Surgical
      technique.
AB  - BACKGROUND: Unicompartmental knee arthroplasty of the medial compartment has
      excellent long-term clinical outcomes. Arthritis isolated to the lateral
      compartment is much less common; subsequently, the clinical outcomes of the
      treatment of that condition are less frequently reported. Most commonly, the
      lateral compartment is approached through a lateral arthrotomy. The purpose of
      this study was to determine the midterm results of lateral unicondylar
      replacement through a medial arthrotomy in patients with primary osteoarthritis
      or posttraumatic arthritis. METHODS: From 1991 to 2004, forty-nine lateral
      unicompartmental knee arthroplasties were performed in forty-five patients by a
      single surgeon. One patient was excluded from the study because of a severe
      underlying neurologic condition. Lateral unicompartmental replacement was
      performed in thirty-eight knees with primary osteoarthritis and in ten knees with
      posttraumatic arthritis secondary to a tibial plateau fracture. Retrospective
      chart reviews and radiographic evaluations were performed, and Knee Society
      scores were determined. RESULTS: The average Knee Society knee and function
      scores improved from 39 and 45 points, respectively, preoperatively to 89 and 80
      points at an average of 5.2 years postoperatively. Preoperative alignment
      averaged 10 degrees of valgus, which was corrected to an average of 6.2 degrees
      of valgus postoperatively. There were no revisions and no notable soft-tissue
      complications. The mean postoperative knee and function scores were significantly
      better for patients with primary osteoarthritis (95 and 86 points, respectively)
      than they were for those with posttraumatic arthritis (74 and 65 points).
      CONCLUSIONS: Lateral unicompartmental knee replacement through a medial approach
      provided durable and reliable short to midterm results. This approach is safe,
      effective, and extensile, making it a viable alternative to a lateral approach.
      The outcomes of lateral unicompartmental replacement in patients with
      posttraumatic arthritis can be expected to be inferior to those in patients with
      primary osteoarthritis.

PMID- 18829934
TI  - Unicondylar osteoarticular allografts of the knee. Surgical technique.
AB  - BACKGROUND: In the management of a resected distal femoral or proximal tibial
      condyle as the result of tumor or trauma, a unicondylar osteoarticular allograft
      is currently the only reconstructive option that avoids the sacrifice of the
      unaffected condyle. The purposes of this study were to perform a survival
      analysis of unicondylar osteoarticular allografts of the knee and to evaluate the
      complications. METHODS: We retrospectively reviewed the results of forty large
      unicondylar osteoarticular allograft procedures in thirty-eight patients who were
      followed for a mean of eleven years. Twenty-nine allografts were femoral
      transplants and included eleven medial and eighteen lateral femoral condyles.
      Eleven allografts were tibial transplants, including four medial and seven
      lateral tibial condyles. The procedure was performed after a tumor resection in
      thirty-six patients and to replace condylar loss after a severe open fracture in
      the remaining two patients. Complications were analyzed, and allograft survival
      from the date of implantation to the date of revision or the time of the latest
      follow-up was determined. Functional and radiographic results were documented
      according to the Musculoskeletal Tumor Society scoring system at the time of the
      latest follow-up. RESULTS: One patient died of tumor-related causes without
      allograft failure before the two-year follow-up evaluation. The global rate of
      allograft survival at both five and ten years was 85%, with a mean follow-up of
      148 months. In six patients, the allografts were removed at an average of twenty
      six months (range, six to forty-eight months) and these were considered failures.
      All six patients underwent a second allograft procedure including two new
      unicondylar and four bicondylar reconstructions. The mean radiographic score for
      the thirty-three surviving allografts evaluated was 89%, with an average
      functional score of 27 of a possible 30 points. CONCLUSIONS: Unicondylar
      osteoarticular allografts of the knee appear to be a reliable alternative for
      patients in whom reconstruction of massive osteoarticular bone loss is limited to
      one condyle of the femur or tibia.

PMID- 18829935
TI  - Femoral nerve block for diaphyseal and distal femoral fractures in the emergency
      department. Surgical technique.
AB  - BACKGROUND: Diaphyseal and distal femoral fractures are painful injuries that are
      frequently seen in patients requiring a trauma work-up in the hospital emergency
      department prior to definitive management. The purpose of this study was to
      determine whether a femoral nerve block administered in the emergency department
      could provide better pain relief for patients with femoral fractures than
      currently used pain management practices. METHODS: Patients who presented with an
      acute diaphyseal or distal femoral fracture were identified as potential
      candidates for this study. Eligible patients were randomized by medical record
      number to receive either (a) the femoral nerve block (20 mL of 0.5% bupivacaine)
      along with standard pain management or (b) standard pain management alone
      (typically intravenous narcotics). The pain was assessed with use of a visual
      analog scale at the initial evaluation and at five, fifteen, thirty, sixty, and
      ninety minutes following the initial evaluation. Fifty-four patients were
      enrolled in the study from April 2005 to May 2006. Thirty-one patients received a
      femoral nerve block, and twenty-three patients received standard pain management
      alone. RESULTS: Baseline scores on the visual analog pain scale did not differ
      between the groups at the initial evaluation. The patients who received a femoral
      nerve block (along with standard pain management) had significantly lower pain
      scores at five, fifteen, thirty, sixty, and ninety minutes following the block
      than did the patients who received standard pain management alone (p < 0.001).
      The score on the visual analog pain scale across these time points was an average
      of 3.6 points less (on a 10-point scale) for those who received the block. There
      were no infections, paresthesias, or other complications related to the femoral
      nerve block. CONCLUSIONS: The acute pain of a diaphyseal or distal femoral
      fracture can be significantly decreased through the use of a femoral nerve block,
      which can be administered safely in the hospital emergency department.

PMID- 18829936
TI  - Sciatic nerve release following fracture or reconstructive surgery of the
      acetabulum. Surgical technique.
AB  - BACKGROUND: Sciatic neuropathy associated with acetabular fractures can result in
      disabling long-term symptoms. The purpose of this retrospective study was to
      evaluate the effect of sciatic nerve release on sciatic neuropathy associated
      with acetabular fractures and reconstructive acetabular surgery. METHODS: Between
      2000 and 2004, ten patients with sciatic neuropathy associated with an acetabular
      fracture were treated with release of the sciatic nerve from scar tissue and
      heterotopic bone. Additional surgical procedures included open reduction and
      internal fixation of the acetabulum (five patients), removal of hardware and
      total hip arthroplasty (three patients), and removal of hardware alone (one
      patient). The average age of the patients was forty-three years. All patients
      were followed with serial examinations and assessments for a minimum of one year
      (average, twenty-six months). RESULTS: All patients had partial to complete
      relief of radicular pain, of diminished sensation, and of paresthesias after the
      nerve release. Four of seven patients with motor loss and two of five patients
      with a footdrop demonstrated improvement in function after the nerve release. No
      patient had evidence of worsening on neurologic examination after the release.
      CONCLUSIONS: Sciatic nerve release during reconstructive acetabular surgery can
      decrease the sensory symptoms of preoperative sciatic neuropathy associated with
      a previous acetabular fracture. Motor symptoms, however, are less likely to
      resolve following nerve release.

PMID- 18829937
TI  - Outcome at forty-five years after open reduction and innominate osteotomy for
      late-presenting developmental dislocation of the hip. Surgical technique.
AB  - BACKGROUND: A consecutive series of seventy-six patients (101 hips) underwent
      primary open reduction, capsulorrhaphy, and innominate osteotomy for late
      presenting developmental dislocation of the hip. They were between 1.5 and five
      years old at the time of surgery, which was done between 1958 and 1965. The
      present study was designed to review the outcome of these patients into middle
      age. METHODS: We located and reviewed the cases of sixty patients (eighty hips),
      which represents a 79% rate of follow-up at forty to forty-eight years
      postoperatively. Nineteen patients (twenty-four hips) had undergone total hip
      replacement, and three (three hips) had died of unrelated causes. The remaining
      thirty-eight patients (fifty-three hips) were assessed by the WOMAC (Western
      Ontario and McMaster Universities Osteoarthritis Index) and Oxford hip score
      questionnaires, physical examination, and a standing anteroposterior pelvic
      radiograph. The radiographs were analyzed to determine the minimum joint space
      width and the Kellgren and Lawrence score. Accepted indices of hip dysplasia were
      measured. RESULTS: With use of Kaplan-Meier survival analysis and with the end
      point defined as total hip replacement, the survival rates at thirty, forty, and
      forty-five years after the reduction were 99% (95% confidence interval, +/-
      2.4%), 86% (95% confidence interval, +/- 6.9%), and 54% (95% confidence interval,
      +/- 16.4%), respectively. The average Oxford hip score and WOMAC score for the
      surviving hips were 16.8 (range, 0 to 82) and 16.7 (range, 0 to 71),
      respectively. Of the fifty-one hips for which radiographs were available, thirty
      eight demonstrated a minimum joint space width of >2.0 mm and thirteen
      demonstrated definite osteoarthritis on the basis of this criterion.
      Osteoarthritis, according to the system of Kellgren and Lawrence, was grade 0 or
      1 in twenty-nine hips, grade 2 in seven hips, and grade 3 or 4 in fifteen hips.
      The average centeredge and acetabular angles were 40 degrees (range, 0 degrees to
      61 degrees ) and 32 degrees (range, 20 degrees to 43 degrees ), respectively.
      With the numbers studied, no significant association was detected between outcome
      and the modifiable risk factors of body mass index or age at the time of surgery.
      Hips in patients with bilateral involvement were at significantly greater risk of
      failure (p = 0.02). CONCLUSIONS: This method of treatment achieves a 54% rate of
      survival of the hip at forty-five years. Two-thirds of the surviving hips have an
      excellent prognosis forty to forty-eight years after the index procedure
      according to the Kellgren and Lawrence score.

PMID- 18829938
TI  - Radial head excision and synovectomy in patients with hemophilia. Surgical
      technique.
AB  - BACKGROUND: Chronic hemophilic synovitis of the elbow usually leads to
      enlargement and erosion of the radial head, resulting in mechanical blockage of
      forearm rotation, synovial impingement, recurrent hemarthrosis, and pain. The
      purpose of the present study was to evaluate the intermediate-term results of
      radial head excision and synovectomy in a large group of patients with hemophilia
      who had been managed at a single institution. METHODS: Information on forty
      radial head excision and synovectomy procedures that had been performed at our
      institution from 1969 to 2004 was retrospectively collected. All but one of the
      operations had been performed in patients with severe hemophilia. The mean age of
      the patients at the time of the procedure was thirty-three years. Pain, limited
      range of motion, and bleeding were the indications for surgery. The mean duration
      of follow-up was 7.7 years. RESULTS: Only one postoperative complication was
      observed: a posterior interosseous nerve palsy that fully resolved by six months.
      No additional surgical intervention for bleeding was required in sixteen of the
      nineteen elbows in which bleeding was one of the indications for surgery. Of the
      forty elbows, seven required a secondary surgical procedure at a mean of five
      years after the excision of the radial head. Examination of the mean range of
      motion at the time of the latest follow-up demonstrated a 63 degrees increase in
      the pronation-supination arc (p < 0.00001) but only a 2 degrees increase in the
      flexion arc. CONCLUSIONS: Radial head excision in patients with hemophilia is an
      effective procedure for improving forearm rotation and reducing pain and bleeding
      frequency, with a low risk of complications.

PMID- 18829939
TI  - Long-term independent evaluation after arthroscopic extra-articular Bankart
      repair with absorbable tacks. Surgical technique.
AB  - BACKGROUND: Several arthroscopic methods have been developed to treat
      posttraumatic recurrent anterior shoulder instability in an attempt to match the
      results that can be achieved with open repair. The aim of this study was to
      perform an independent long-term clinical and radiographic evaluation after extra
      articular arthroscopic Bankart repair with use of absorbable tacks (Suretac
      fixators). METHODS: Eighty-one consecutive patients with posttraumatic recurrent
      anterior shoulder instability underwent an extra-articular arthroscopic Bankart
      procedure. Seventy-one (88%) of the patients were reexamined physically after a
      median duration of follow-up of 107 months by two independent examiners and
      constituted the study group. Their clinical and radiographic outcomes were
      documented. RESULTS: At the time of follow-up, twenty-seven (38%) of the seventy
      one patients had experienced some kind of shoulder instability, although fifteen
      of them had had a new, clinically relevant shoulder injury. Eleven patients had
      had subluxation only, and sixteen had had redislocation. Fourteen of the twenty
      seven patients had had a single episode of instability. Seven patients had
      undergone additional surgery to treat shoulder instability. The instability
      episodes occurred less than two years postoperatively in nine patients, between
      two and five years postoperatively in twelve, and more than five years
      postoperatively in six. At the time of final follow-up, the median external
      rotation in abduction was 90 degrees (range, 0 degrees to 120 degrees ) compared
      with 95 degrees (range, 70 degrees to 125 degrees ) for the contralateral,
      uninjured shoulders (p < 0.001). Before the injury, fifty-two patients (73%)
      participated in overhead or contact sports, whereas thirty-four patients (45%)
      participated in such activities at the time of follow-up. At the time of follow
      up, the drill holes used to implant the absorbable tacks were invisible or hardly
      visible in fifty-eight (91%) of sixty-four patients for whom radiographs had been
      made. A marked increase in degenerative changes was noted when follow-up
      radiographs were compared with the preoperative radiographs. CONCLUSIONS: This
      long-term follow-up study of arthroscopic extra-articular Bankart repairs
      revealed an unexpectedly high number of patients with new episodes of
      instability. This finding led to a slight modification of the technique. Since
      most instability episodes occurred after two years, it is important to follow
      patients for a longer period of time after surgical treatment of recurrent
      anterior shoulder instability to identify the true recurrence rate.

PMID- 18829940
TI  - The outcome and structural integrity of arthroscopic rotator cuff repair with use
      of the double-row suture anchor technique. Surgical technique.
AB  - BACKGROUND: The reported rate of failure after arthroscopic rotator cuff repair
      has varied widely. The influence of the repair technique on the failure rates and
      functional outcomes after open or arthroscopic rotator cuff repair remains
      controversial. The purpose of the present study was to evaluate the functional
      and anatomic results of arthroscopic rotator cuff repairs performed with the
      double-row suture anchor technique on the basis of computed tomography or
      magnetic resonance imaging arthrography in order to determine the postoperative
      integrity of the repairs. METHODS: A prospective series of 105 consecutive
      shoulders undergoing arthroscopic double-row rotator cuff repair of the
      supraspinatus or a combination of the supraspinatus and infraspinatus were
      evaluated at a minimum of two years after surgery. The evaluation included a
      routine history and physical examination as well as determination of the
      preoperative and postoperative strength, pain, range of motion, and Constant
      scores. All shoulders had a preoperative and postoperative computed tomography
      arthrogram (103 shoulders) or magnetic resonance imaging arthrogram (two
      shoulders). RESULTS: There were thirty-six small rotator cuff tears, forty-seven
      large isolated supraspinatus or combined supraspinatus and infraspinatus tendon
      tears, and twenty-two massive rotator cuff tears. The mean Constant score (and
      standard deviation) was 43.2 +/- 15.1 points (range, 8 to 83 points)
      preoperatively and 80.1 +/- 11.1 points (range, 46 to 100 points)
      postoperatively. Twelve of the 105 repairs failed. Intact rotator cuff repairs
      were associated with significantly increased strength and active range of motion.
      CONCLUSIONS: Arthroscopic repair of a rotator cuff tear with use of the double
      row suture anchor technique results in a much lower rate of failure than has
      previously been reported in association with either open or arthroscopic repair
      methods. Patients with an intact rotator cuff repair have better pain relief than
      those with a failed repair. After repair, large and massive rotator cuff tears
      result in more postoperative weakness than small tears do.

PMID- 18829941
TI  - The DUROM cup humeral surface replacement in patients with rheumatoid arthritis.
      Surgical technique.
AB  - BACKGROUND: Rheumatoid arthritis often leads to severe destruction of the
      glenohumeral joint, including synovitis and inflammation-induced alterations of
      the rotator cuff. Cup arthroplasty, or surface replacement of the shoulder, was
      introduced in the 1980s. The aim of this study was to evaluate the midterm
      results of the DUROM cup surface replacement for patients with rheumatoid
      arthritis affecting the glenohumeral joint. METHODS: From 1997 to 2000, forty-two
      DUROM cup hemiprostheses were implanted in a cohort of thirty-five patients
      (forty-two shoulders), who were evaluated preoperatively and again at three,
      twelve, and more than sixty months postoperatively. Six patients (seven
      shoulders) were lost to follow-up. Thirty-five shoulders in twenty-nine patients
      (twenty-one women and eight men with an average age of 61.4 years) could be
      evaluated prospectively after an average follow-up period of 73.1 months.
      Patients were evaluated clinically with the use of the Constant score, and a
      detailed radiographic analysis was performed to determine the presence of
      endoprosthetic loosening, glenohumeral subluxation, and glenoid bone loss.
      RESULTS: The mean Constant score for the thirty-five shoulders increased from
      20.8 points preoperatively to 64.3 points at a mean of 73.1 months
      postoperatively. There were three revisions: one to replace an implant that was
      too large, another to treat glenoid erosion, and a third due to loosening of the
      implant. No additional cases of loosening of the prosthesis or changes in cup
      position were observed radiographically. Over the five-year follow-up period,
      proximal migration of the cup increased in 63% of the shoulders, and glenoid
      depth increased in 31%. With the numbers studied, no differences in clinical
      outcome were identified between patients with a massive rotator cuff tear and
      those with a smaller or no tear. CONCLUSIONS: The midterm results of the cemented
      DUROM cup surface replacement for patients with advanced rheumatoid arthritis of
      the shoulder are very encouraging, even for patients with a massive tear of the
      rotator cuff. The advantage of this cup arthroplasty is the less complex bone
      sparing surgery. In the event of failure of the implant, other reliable salvage
      options remain available.

PMID- 18829942
TI  - Proximally based conjoined tendon transfer for coracoclavicular reconstruction in
      the treatment of acromioclavicular dislocation. Surgical technique.
AB  - BACKGROUND: We report an alternative to the modified Weaver-Dunn technique that
      can achieve stable coracoclavicular reconstruction while avoiding sacrifice of
      the coracoacromial arch. The purpose of this study was to retrospectively analyze
      the functional outcomes and radiographic features of patients treated with
      coracoclavicular ligament reconstruction with use of a proximally based conjoined
      tendon transfer. METHODS: The cases of thirty-eight patients with type-IV, type
      V, and selected type-III acromioclavicular dislocations according to the Rockwood
      classification system, who were followed for an average follow-up of 38.7 months,
      were evaluated retrospectively. Transfer of the lateral half of the conjoined
      tendon to the distal aspect of the clavicle in a proximally based fashion, with
      additional coracoclavicular fixation, was performed in all patients. At the
      latest follow-up evaluation, radiographic analysis and the scores on the American
      Shoulder and Elbow Surgeons, Constant and Murley, and Simple Shoulder Test
      questionnaires were used to provide a final evaluation of shoulder function. The
      ability to return to work and the ability to return to sports were also recorded.
      RESULTS: At the time of final follow-up, the mean American Shoulder and Elbow
      Surgeons score was 91.4, with a mean pain score on the visual analog scale of
      1.8, mean forward flexion of 148.2 degrees , and mean external rotation of 38.0
      degrees . The mean Constant and Murley score was 90.6. The new number of positive
      answers on the Simple Shoulder Test was 10.9. The overall rate of satisfaction
      (an excellent or good result) was 89% (thirty-four patients). Thirty-five (92%)
      of the thirty-eight patients returned to their previous work, and thirty-two
      (84%) returned to their preinjury level of sports. CONCLUSIONS: The proximally
      based conjoined tendon transfer is a reliable treatment for a high-grade
      acromioclavicular dislocation. The lateral half of the conjoined tendon is a safe
      graft source with ample length, and this technique avoids sacrifice of the
      coracoacromial ligament.

PMID- 18829943
TI  - Expression of mRNA for galanin, galanin-like peptide and galanin receptors 1-3 in
      the ovine hypothalamus and pituitary gland: effects of age and gender.
AB  - The neurotransmitters/neuromodulators galanin (GAL) and galanin-like peptide
      (GALP) are known to operate through three G protein-coupled receptors, GALR1,
      GALR2 and GALR3. The aim of this study was to investigate changes in expression
      of mRNA for galanin, GALP and GALR1-3 in the hypothalamus and pituitary gland, of
      male and female sheep, to determine how expression changed in association with
      growth and the attainment of reproductive competence. Tissue samples from the
      hypothalami and pituitary glands were analysed from late foetal and pre-pubertal
      lambs and adult sheep. Although mRNA for galanin and GALR1-3 was present in both
      tissues, at all ages and in both genders, quantification of GALP mRNA was not
      possible due to its low levels of expression. mRNA expression for both galanin
      and its receptors was seen to change significantly in both tissues as a function
      of age. Specifically, hypothalamic galanin mRNA expression increased with age in
      the male, but decreased with age in the female pituitary gland. mRNA expression
      for all receptors increased between foetal and pre-pubertal age groups and
      decreased significantly between pre-pubertal and adult animals. The results
      indicate that the expression of mRNA for galanin and its receptors changes
      dynamically with age and those significant differences exist with regard to
      tissue type and gender. These changes suggest that galaninergic neuroendocrine
      systems could be involved in the regulation of ovine growth and or the
      development of reproductive competence. The roles played by these systems in the
      sheep, however, may differ from other species, in particular the neuroendocrine
      link between nutrition and reproduction and GALR1's role in pituitary signalling.

PMID- 18829944
TI  - Lysophosphatic acid modulates prostaglandin secretion in the bovine uterus.
AB  - Lysophosphatidic acid (LPA) modulates prostaglandin (PG) synthesis via LPA
      receptor 3 (LPAR3) in the murine endometrium. The lack of functional LPAR3 in
      mice may lead to embryo mortality. In the present study, we examined the role of
      LPA in the bovine uterus. We confirmed that LPA is locally produced and released
      from the bovine endometrium. Moreover, there are enzymes involved in LPA
      synthesis (phospholipase (PL) D(2) and PLA2G1B) in the bovine endometrium during
      estrous cycle and early pregnancy. Expression of the receptor for LPA (LPAR1) was
      positively correlated with the expression of PGE(2) synthase (PGES) and
      negatively correlated with the expression of PGF(2alpha) synthase (aldose
      reductase with 20 alpha-hydroxysteroid dehydrogenase activity - PGFS) during
      early pregnancy. In vivo LPA induced P4 and PGE(2) secretion was inhibited by
      LPAR1 antagonist (Ki16425). The overall results indicate that LPA is locally
      produced and released from the bovine endometrium. Moreover, LPAR1 gene
      expression in the endometrium during the estrous cycle and early pregnancy
      indicates that LPA may play autocrine and/or paracrine roles in the bovine
      uterus. LPAR1 gene expression is positively correlated with the expression of the
      enzyme responsible for luteotropic PGE(2) production (PGES) in endometrium. In
      cow, LPA stimulates P4 and PGE(2) secretion. Thus, LPA in the bovine reproductive
      tract may indirectly (via endometrium) or directly support corpus luteum action
      via the increase of P4 synthesis and the increase of PGE(2)/PGF(2)(alpha) ratio.
      It suggests that LPA may serve as an important factor in the maintenance of early
      pregnancy in cow.

PMID- 18829945
TI  - Decreased oocyte-granulosa cell gap junction communication and connexin
      expression in a type 1 diabetic mouse model.
AB  - In women, type 1 diabetes is associated with an increased risk of poor prenatal
      outcomes such as congenital anomalies and early miscarriage. In murine models of
      type 1 diabetes, impaired oocyte meiotic maturation, abnormal oocyte metabolism,
      and increased granulosa cell apoptosis have been noted. because gap junction
      communication is critical for the regulation of oocyte growth and meiotic
      maturation, we investigated the level of communication between the oocyte and
      surrounding cumulus cells in a streptozotocin-induced type 1 diabetic B6SJL/F1
      mouse model and the expression of gap junction proteins known as connexins.
      Fluorescence recovery after photobleaching analyses of cumulus cell-enclosed
      oocytes (CEOs) from diabetic mice showed a 60% decrease in communication as
      compared with CEOs from nondiabetic mice. Real-time RT-PCR analyses confirmed the
      presence of Cx26, Cx37, and Cx57 mRNA and revealed a significant decrease in Cx37
      mRNA expression in oocytes from diabetic mice compared with nondiabetic mice.
      Western analyses detected Cx26 expression in CEO but not denuded oocyte (DO)
      samples, and Cx37 in DO samples. Cx26 protein levels were decreased by 78% in
      CEOs from diabetic mice, and Cx37 protein levels were decreased 36% in DOs from
      diabetic mice. This decrease in connexin expression and gap junction
      communication in CEOs from diabetic mice may be responsible for the impaired
      oocyte meiotic maturation and poor pregnancy outcomes.

PMID- 18829946
TI  - Effect of acute exposure to a complex fragrance on lexical decision performance.
AB  - This study tested the effect of acute exposure to a commercial air freshener,
      derived from fragrant botanical extracts, at an average concentration of 3.16
      mg/m(3) total volatile organic compounds on the lexical decision performance of
      28 naive participants. Participants attended two 18-min sessions on separate days
      and were continuously exposed to the fragrance in either the first (F/NF) or
      second (NF/F) session. Participants were not instructed about the fragrance.
      Exposure to the fragrance did not affect high-frequency word recognition.
      However, there was an order of administration effect for low-frequency word
      recognition accuracy. When the fragrance was administered first before the no
      odor control condition, it did not affect accuracy, but when it was administered
      second after the control condition, it significantly decreased low-frequency word
      recognition accuracy. Reaction times to low-frequency words were significantly
      slower than those for high-frequency words, but no effect of either fragrance or
      order of administration on reaction times was found. The presence of fragrance in
      the second session apparently served as a distraction that impaired lexical task
      performance accuracy. The introduction of fragrances into buildings may not
      necessarily facilitate all aspects of work performance as anticipated.

PMID- 18829947
TI  - Reactivation in ventral striatum during hippocampal ripples: evidence for the
      binding of reward and spatial memories?

PMID- 18829948
TI  - Bidirectional regulation of the cAMP response element binding protein encodes
      spatial map alignment in prism-adapting barn owls.
AB  - The barn owl midbrain contains mutually aligned maps of auditory and visual
      space. Throughout life, map alignment is maintained through the actions of an
      instructive signal that encodes the magnitude of auditory-visual mismatch. The
      intracellular signaling pathways activated by this signal are unknown. Here we
      tested the hypothesis that CREB (cAMP response element-binding protein) provides
      a cell-specific readout of instructive information. Owls were fitted with
      prismatic or control spectacles and provided rich auditory-visual experience:
      hunting live mice. CREB activation was analyzed within 30 min of hunting using
      phosphorylation state-specific CREB (pCREB) and CREB antibodies, confocal
      imaging, and immunofluorescence measurements at individual cell nuclei. In
      control owls or prism-adapted owls, which experience small instructive signals,
      the frequency distributions of pCREB/CREB values obtained for cell nuclei within
      the external nucleus of the inferior colliculus (ICX) were unimodal. In contrast,
      in owls adapting to prisms or readapting to normal conditions, the distributions
      were bimodal: certain cells had received a signal that positively regulated CREB
      and, by extension, transcription of CREB-dependent genes, whereas others received
      a signal that negatively regulated it. These changes were restricted to the
      subregion of the inferior colliculus that received optically displaced input, the
      rostral ICX, and were not evident in the caudal ICX or central nucleus. Finally,
      the topographic pattern of CREB regulation was patchy, not continuous, as
      expected from the actions of a topographically precise signal encoding discrete
      events. These results support a model in which the magnitude of CREB activation
      within individual cells provides a readout of the instructive signal that guides
      plasticity and learning.

PMID- 18829949
TI  - Upregulation of calcium/calmodulin-dependent protein kinase IV improves memory
      formation and rescues memory loss with aging.
AB  - Previous studies have suggested that calcium/calmodulin-dependent protein kinase
      IV (CaMKIV) functions as a positive regulator for memory formation and that age
      related memory deficits are the result of dysfunctional signaling pathways
      mediated by cAMP response element-binding protein (CREB), the downstream
      transcription factor of CaMKIV. Little is known, however, about the effects of
      increased CaMKIV levels on the ability to form memory in adult and aged stages.
      We generated a transgenic mouse overexpressing CaMKIV in the forebrain and showed
      that the upregulation of CaMKIV led to an increase in learning-induced CREB
      activity, increased learning-related hippocampal potentiation, and enhanced
      consolidation of contextual fear and social memories. Importantly, we also
      observed reduced hippocampal CaMKIV expression with aging and a correlation
      between CaMKIV expression level and memory performance in aged mice. Genetic
      overexpression of CaMKIV was able to rescue associated memory deficits in aged
      mice. Our findings suggest that the level of CaMKIV expression correlates
      positively with the ability to form long-term memory and implicate the decline of
      CaMKIV signaling mechanisms in age-related memory deficits.

PMID- 18829950
TI  - Intrabulbar projecting external tufted cells mediate a timing-based mechanism
      that dynamically gates olfactory bulb output.
AB  - In the mammalian olfactory system, intrabulbar projections (IBPs) mediated by a
      class of external tufted cells (ET cells) specifically link isofunctional odor
      columns within the same olfactory bulb. To study the function of these ET cells
      within the glomerular network, we developed a "hemibulb" preparation that
      maintains IBPs intact enabling the select activation of ET cells associated with
      specific glomeruli. Using P2-GFP mice, a line in which the P2 glomeruli are
      labeled with green fluorescent protein, we recorded from P2 mitral cells (MT
      cells) while selectively stimulating P2 ET cells. Here, we show that ET-cell
      activity evokes a slow modulatory (SM) potential within MT cells, which is
      mediated by the glomerular network and consists of both excitatory and inhibitory
      components. Interestingly, the timing of the SM potential with respect to
      olfactory nerve (ON) stimulation can produce converse effects on MT-cell output.
      When ET-cell activity precedes ON stimulation, the MT-cell response is
      potentiated; however, when ET-cell activity follows ON stimulation, the MT-cell
      response is inhibited. Thus, intrabulbar projecting ET cells can shape olfactory
      bulb output through intraglomerular modulation of MT cells.

PMID- 18829951
TI  - Drosophila painless is a Ca2+-requiring channel activated by noxious heat.
AB  - Thermal changes activate some members of the transient receptor potential (TRP)
      ion channel super family. They are primary sensors for detecting environmental
      temperatures. The Drosophila TRP channel Painless is believed responsible for
      avoidance of noxious heat because painless mutant flies display defects in heat
      sensing. However, no studies have proven its heat responsiveness. We show that
      Painless expressed in human embryonic kidney-derived 293 (HEK293) cells is a
      noxious heat-activated, Ca(2+)-permeable channel, and the function is mostly
      dependent on Ca(2+). In Ca(2+)-imaging, Painless mediated a robust intracellular
      Ca(2+) (Ca(2+)(i)) increase during heating, and it showed heat-evoked inward
      currents in whole-cell patch-clamp mode. Ca(2+) permeability was much higher than
      that of other cations. Heat-evoked currents were negligible in the absence of
      extracellular Ca(2+) (Ca(2+)(o)) and Ca(2+)(i), whereas 200 nm Ca(2+)(i) enabled
      heat activation of Painless. Activation kinetics were significantly accelerated
      in the presence of Ca(2+)(i). The temperature threshold for Painless activation
      was 42.6 degrees C in the presence of Ca(2+)(i), whereas the threshold was
      significantly increased to 44.1 degrees C when only Ca(2+)(o) was present.
      Temperature thresholds were further reduced after repetitive heating in a Ca(2+)
      dependent manner. Ca(2+)-dependent heat activation of Painless was observed at
      the single-channel level in excised membranes. We found that a Ca(2+)-regulatory
      site is located in the N-terminal region of Painless. Painless-expressing HEK293
      cells were insensitive to various thermosensitive TRP channel activators
      including allyl isothiocyanate, whereas mammalian TRPA1 inhibitors, ruthenium
      red, and camphor, reversibly blocked heat activation of Painless. Our results
      demonstrate that Painless is a direct sensor for noxious heat in Drosophila.

PMID- 18829952
TI  - Aminoglycoside-induced phosphatidylserine externalization in sensory hair cells
      is regionally restricted, rapid, and reversible.
AB  - The aminophospholipid phosphatidylserine (PS) is normally restricted to the inner
      leaflet of the plasma membrane. During certain cellular processes, including
      apoptosis, PS translocates to the outer leaflet and can be labeled with
      externally applied annexin V, a calcium-dependent PS-binding protein. In mouse
      cochlear cultures, annexin V labeling reveals that the aminoglycoside antibiotic
      neomycin induces rapid PS externalization, specifically on the apical surface of
      hair cells. PS externalization is observed within approximately 75 s of neomycin
      perfusion, first on the hair bundle and then on membrane blebs forming around the
      apical surface. Whole-cell capacitance also increases significantly within
      minutes of neomycin application, indicating that blebbing is accompanied by
      membrane addition to the hair cell surface. PS externalization and membrane
      blebbing can, nonetheless, occur independently. Pretreating hair cells with
      calcium chelators, a procedure that blocks mechanotransduction, or overexpressing
      a phosphatidylinositol 4,5-biphosphate (PIP2)-binding pleckstrin homology domain,
      can reduce neomycin-induced PS externalization, suggesting that neomycin enters
      hair cells via transduction channels, clusters PIP2, and thereby activates lipid
      scrambling. The effects of short-term neomycin treatment are reversible. After
      neomycin washout, PS is no longer detected on the apical surface, apical membrane
      blebs disappear, and surface-bound annexin V is internalized, distributing
      throughout the supranuclear cytoplasm of the hair cell. Hair cells can therefore
      repair, and recover from, neomycin-induced surface damage. Hair cells lacking
      myosin VI, a minus-end directed actin-based motor implicated in endocytosis, can
      also recover from brief neomycin treatment. Internalized annexin V, however,
      remains below the apical surface, thereby pinpointing a critical role for myosin
      VI in the transport of endocytosed material away from the periphery of the hair
      cell.

PMID- 18829953
TI  - Role of GluR1 in activity-dependent motor system development.
AB  - Activity-dependent specification of neuronal architecture during early postnatal
      life is essential for refining the precision of communication between neurons. In
      the spinal cord under normal circumstances, the AMPA receptor subunit GluR1 is
      expressed at high levels by motor neurons and surrounding interneurons during
      this critical developmental period, although the role it plays in circuit
      formation and locomotor behavior is unknown. Here, we show that GluR1 promotes
      dendrite growth in a non-cell-autonomous manner in vitro and in vivo. The mal
      development of motor neuron dendrites is associated with changes in the pattern
      of interneuronal connectivity within the segmental spinal cord and defects in
      strength and endurance. Transgenic expression of GluR1 in adult motor neurons
      leads to dendrite remodeling and supernormal locomotor function. GluR1 expression
      by neurons within the segmental spinal cord plays an essential role in formation
      of the neural network that underlies normal motor behavior.

PMID- 18829954
TI  - Perceptual systems controlling speech production.
AB  - It is proposed that the acquisition and maintenance of fluent speech depend on
      the rapid temporal integration of motor feedforward and polysensory (auditory and
      somatosensory) feedback signals. In a functional magnetic resonance imaging study
      on 21 healthy right-handed, English-speaking volunteers, we investigated activity
      within these motor and sensory pathways and their integration during speech. Four
      motor conditions were studied: two speech conditions (propositional and
      nonpropositional speech) and two silent conditions requiring repetitive movement
      of the principal articulators (jaw and tongue movements). The scanning technique
      was adapted to minimize artifact associated with overt speech production. Our
      result indicates that this multimodal convergence occurs within the left and
      right supratemporal planes (STPs), with peaks of activity at their posteromedial
      extents, in regions classically considered as unimodal auditory association
      cortex. This cortical specialization contrasted sharply with the response of
      somatosensory association cortex (SII), in which activity was suppressed during
      speech but not during the silent repetitive movement of the principal
      articulators. It was also clearly distinct from the response of lateral auditory
      association cortex, which responded to auditory feedback alone, and from that
      within a left lateralized ventrolateral temporal and inferior frontal system,
      which served lexical- and sentence-level language retrieval. This response of
      cortical regions related to speech production is not predicted by the classical
      model of hierarchical cortical processing, providing new insights into the role
      of the STP in polysensory integration and into the modulation of activity in SII
      during normal speech production. These findings have novel implications for the
      acquisition and maintenance of fluent speech.

PMID- 18829955
TI  - Neuronal mechanisms of cortical alpha oscillations in awake-behaving macaques.
AB  - Field potential oscillations at approximately 10 Hz (alpha rhythm) are widely
      noted in the visual cortices, but their physiological mechanisms and significance
      are poorly understood. In vitro studies have implicated pyramidal neurons in both
      infragranular and supragranular layers as pacemakers. The generality of these
      observations for the intact brain in the behaving subject is unknown. We analyzed
      laminar profiles of spontaneous local field potentials and multiunit activity
      (MUA) recorded with linear array multielectrodes from visual areas V2, V4, and
      inferotemporal (IT) cortex of two macaque monkeys during performance of a sensory
      discrimination task. Current source density (CSD) analysis was combined with CSD
      MUA coherence to identify intracortical alpha current generators and their
      potential for alpha pacemaking. The role of each alpha current generator was
      further delineated by Granger causality analyses. In V2 and V4, alpha current
      generators were found in all layers, with the infragranular generator acting as
      primary local pacemaking generator. In contrast, in IT, alpha current generators
      were found only in supragranular and infragranular layers, with the supragranular
      generator acting as primary local pacemaking generator. The amplitude of alpha
      activity in V2 and V4 was negatively correlated with behavioral performance,
      whereas the opposite was true in IT. The alpha rhythm in IT thus appears to
      differ from that in the lower-order cortices, both in terms of its underlying
      physiological mechanism and its behavioral correlates. This work may help to
      reconcile some of the diverse findings and conclusions on the functional
      significance of alpha band oscillations in the visual system.

PMID- 18829956
TI  - Brain SIRT1: anatomical distribution and regulation by energy availability.
AB  - SIRT1 is a nicotinamide adenosine dinucleotide-dependent deacetylase that
      orchestrates key metabolic adaptations to nutrient deprivation in peripheral
      tissues. SIRT1 is induced also in the brain by reduced energy intake. However,
      very little is known about SIRT1 distribution and the biochemical phenotypes of
      SIRT1-expressing cells in the neuraxis. Unknown are also the brain sites in which
      SIRT1 is regulated by energy availability and whether these regulations are
      altered in a genetic model of obesity. To address these issues, we performed in
      situ hybridization histochemistry analyses and found that Sirt1 mRNA is highly
      expressed in metabolically relevant sites. These include, but are not limited to,
      the hypothalamic arcuate, ventromedial, dorsomedial, and paraventricular nuclei
      and the area postrema and the nucleus of the solitary tract in the hindbrain. Of
      note, our single-cell reverse transcription-PCR analyses revealed that Sirt1 mRNA
      is expressed in pro-opiomelanocortin neurons that are critical for normal body
      weight and glucose homeostasis. We also found that SIRT1 protein levels are
      restrictedly increased in the hypothalamus in the fasted brain. Of note, we found
      that this hypothalamic-specific, fasting-induced SIRT1 regulation is altered in
      leptin-deficient, obese mice. Collectively, our findings establish the
      distribution of Sirt1 mRNA throughout the neuraxis and suggest a previously
      unrecognized role of brain SIRT1 in regulating energy homeostasis.

PMID- 18829957
TI  - Frequency-selective coding of translation and tilt in macaque cerebellar nodulus
      and uvula.
AB  - Spatial orientation depends critically on the brain's ability to segregate linear
      acceleration signals arising from otolith afferents into estimates of self-motion
      and orientation relative to gravity. In the absence of visual information, this
      ability is known to deteriorate at low frequencies. The cerebellar nodulus/uvula
      (NU) has been shown to participate in this computation, although its exact role
      remains unclear. Here, we show that NU simple spike (SS) responses also exhibit a
      frequency dependent selectivity to self-motion (translation) and spatial
      orientation (tilt). At 0.5 Hz, Purkinje cells encode three-dimensional
      translation and only weakly modulate during pitch and roll tilt (0.4 +/- 0.05
      spikes/s/degrees/s). But this ability to selectively signal translation over tilt
      is compromised at lower frequencies, such that at 0.05 Hz tilt response gains
      average 2.0 +/- 0.3 spikes/s/degrees/s. We show that such frequency-dependent
      properties are attributable to an incomplete cancellation of otolith-driven SS
      responses during tilt by a canal-driven signal coding angular position with a
      sensitivity of 3.9 +/- 0.3 spikes/s/degrees. This incomplete cancellation is
      brought about because otolith-driven SS responses are also partially integrated,
      thus encoding combinations of linear velocity and acceleration. These results are
      consistent with the notion that NU SS modulation represents an internal neural
      representation of similar frequency dependencies seen in behavior.

PMID- 18829958
TI  - HIV-1 clade-specific differences in the induction of neuropathogenesis.
AB  - Human immunodeficiency virus (HIV)-associated dementia (HAD) is common among
      clade B HIV-infected individuals, but less common and less severe among
      individuals infected with clade C HIV-1, suggesting clade-specific differences in
      neuropathogenicity. Although differences in neuropathogenicity have been
      investigated in vitro using viral proteins responsible for HAD, to date there are
      no virological studies using animal models to address this issue. Therefore, we
      investigated neuropathogenesis induced by HIV-1 clades using the severe combined
      immune deficiency (SCID) mouse HIV encephalitis model, which involves
      intracranial injection of macrophages infected with representative clade B (HIV
      1(ADA)) or clade C (HIV-1(Indie-C1)) HIV-1 isolates into SCID mice. In cognitive
      tests, mice exposed to similar inputs of HIV-1 clade C made fewer memory errors
      than those exposed to HIV-1 clade B. Histopathological analysis of mice exposed
      to clade B exhibited greater astrogliosis and increased loss of neuronal network
      integrity. In vitro experiments revealed differences in a key characteristic of
      HIV-1 that influences HAD, increased monocyte infiltration. HIV-1(Indie-C1)
      infected macrophages recruited monocytes poorly in vitro compared with HIV-1(ADA)
      infected macrophages. Monocyte recruitment was HIV-1 Tat and CCL2 dependent. This
      is the first demonstration, ever since HIV neuropathogenesis was first
      recognized, that viral genetic differences between clades can affect disease
      severity and that such studies help identify key players in neuropathogenesis by
      HIV-1.

PMID- 18829959
TI  - Rhythmically active enkephalin-expressing GABAergic cells in the CA1 area of the
      hippocampus project to the subiculum and preferentially innervate interneurons.
AB  - Enkephalins (ENKs) are endogenous opioids that regulate synaptic excitability of
      GABAergic networks in the cerebral cortex. Using retrograde tracer injections in
      the subiculum, we identified a hippocampal population of ENK-expressing
      projection neurons. In situ hybridization for GAD shows that ENK-expressing cells
      are a small GABAergic subpopulation. Furthermore, by extracellular recording and
      juxtacellular labeling in vivo, we identified an ENK-expressing cell in stratum
      radiatum of the CA1 area by its complete axodendritic arborization and
      characteristic spike timing during network oscillations. The somatodendritic
      membrane was immunopositive for mGluR1alpha, and there was both a rich local axon
      in CA1 and subicular-projecting branches. The boutons showed cell-type- and layer
      specific innervation, i.e., interneurons were the main targets in the alveus,
      both interneurons and pyramidal cell dendrites were innervated in the other
      layers, and interneurons were exclusive targets in the subiculum. Parvalbumin-,
      but not somatostatin-, calbindin-, or cholecystokinin-expressing interneurons
      were preferred synaptic targets. During network activity, the juxtacellularly
      labeled ENK-expressing cell was phase modulated throughout theta oscillations,
      but silenced during sharp-wave/ripple episodes. After these episodes the
      interneuron exhibited rebound activity of high-frequency spike bursts, presumably
      causing peptide release. The ENK-expressing interneurons innervating parvalbumin
      positive interneurons might contribute to the organization of the sharp
      wave/ripple episodes by decreased firing during and rebound activity after the
      ripple episodes, as well as to the coordination of activity between the CA1 and
      subicular areas during network oscillations.

PMID- 18829960
TI  - Moment-to-moment tracking of state value in the amygdala.
AB  - As an organism interacts with the world, how good or bad things are at the
      moment, the value of the current state of the organism, is an important parameter
      that is likely to be encoded in the brain. As the environment changes and new
      stimuli appear, estimates of state value must be updated to support appropriate
      responses and learning. Indeed, many models of reinforcement learning posit
      representations of state value. We examined how the brain mediates this process
      by recording amygdala neural activity while monkeys performed a trace
      conditioning task requiring fixation. The presentation of different stimuli
      induced state transitions; these stimuli included unconditioned stimuli (USs)
      (liquid rewards and aversive air puffs), newly learned reinforcement-predictive
      visual stimuli [conditioned stimuli (CSs)], and familiar stimuli long associated
      with reinforcement [fixation point (FP)]. The FP had a positive value to monkeys,
      because they chose to foveate it to initiate trials. Different populations of
      amygdala neurons tracked the positive or negative value of the current state,
      regardless of whether state transitions were caused by the FP, CSs, or USs.
      Positive value-coding neurons increased their firing during the fixation interval
      and fired more strongly after rewarded CSs and rewards than after punished CSs
      and air puffs. Negative value-coding neurons did the opposite, decreasing their
      firing during the fixation interval and firing more strongly after punished CSs
      and air puffs than after rewarded CSs and rewards. This representation of state
      value could underlie how the amygdala helps coordinate cognitive, emotional, and
      behavioral responses depending on the value of one's state.

PMID- 18829961
TI  - The actin-binding protein Abp1 controls dendritic spine morphology and is
      important for spine head and synapse formation.
AB  - Polymerization and organization of actin into complex superstructures, including
      those found in dendritic spines, is indispensable for structure and function of
      neuronal networks. Here we show that the filamentous actin (F-actin)-binding
      protein 1 (Abp1), which controls Arp2/3 complex-mediated actin nucleation and
      binds to postsynaptic scaffold proteins of the ProSAP (proline-rich synapse
      associated protein 1)/Shank family, has a profound impact on synaptic
      organization. Overexpression of the two Abp1 F-actin-binding domains increases
      the length of thin, filopodia-like and mushroom-type spines but dramatically
      reduces mushroom spine density, attributable to lack of the Abp1 Src homology 3
      (SH3) domain. In contrast, overexpression of full-length Abp1 increases mushroom
      spine and synapse density. The SH3 domain alone has a dominant-negative effect on
      mushroom spines, whereas the density of filopodia and thin, immature spines
      remains unchanged. This suggests that both actin-binding and SH3 domain
      interactions are crucial for the role of Abp1 in spine maturation. Indeed, Abp1
      knockdown significantly reduces mushroom spine and synapse density. Abp1 hereby
      works in close conjunction with ProSAP1/Shank2 and ProSAP2/Shank3, because Abp1
      effects were suppressed by ProSAP2 RNA interference and the ProSAP/Shank-induced
      increase of spine head width is further promoted by Abp1 cooverexpression and
      reduced on Abp1 knockdown. Also, interfering with the formation of functional
      Abp1-ProSAP protein complexes prevents ProSAP-mediated spine head extension.
      Spine head extension furthermore depends on local Arp2/3 complex-mediated actin
      polymerization, which is controlled by Abp1 via the Arp2/3 complex activator N
      WASP (neural Wiskott-Aldrich syndrome protein). Abp1 thus plays an important role
      in the formation and morphology control of synapses by making a required
      functional connection between postsynaptic density components and postsynaptic
      actin dynamics.

PMID- 18829962
TI  - Does learned shape selectivity in inferior temporal cortex automatically
      generalize across retinal position?
AB  - Biological visual systems have the remarkable ability to recognize objects
      despite confounding factors such as object position, size, pose, and lighting. In
      primates, this ability likely results from neuronal responses at the highest
      stage of the ventral visual stream [inferior temporal cortex (IT)] that signal
      object identity while tolerating these factors. However, for even the apparently
      simplest IT tolerance ("invariance"), tolerance to object position on the retina,
      little is known about how this feat is achieved. One possibility is that IT
      position tolerance is innate in that discriminatory power for newly learned
      objects automatically generalizes across position. Alternatively, visual
      experience plays a role in developing position tolerance. To test these ideas, we
      trained adult monkeys in a difficult object discrimination task in which their
      visual experience with novel objects was restricted to a single retinal position.
      After training, we recorded the spiking activity of an unbiased population of IT
      neurons and found that it contained significantly greater selectivity among the
      newly learned objects at the experienced position compared with a carefully
      matched, non-experienced position. Interleaved testing with other objects shows
      that this difference cannot be attributed to a bias in spatial attention or
      neuronal sampling. We conclude from these results that, at least under some
      conditions, full transfer of IT neuronal selectivity across retinal position is
      not automatic. This finding raises the possibility that visual experience plays a
      role in building neuronal tolerance in the ventral visual stream and the
      recognition abilities it supports.

PMID- 18829963
TI  - Top-down control of human visual cortex by frontal and parietal cortex in
      anticipatory visual spatial attention.
AB  - Advance information about an impending stimulus facilitates its subsequent
      identification and ensuing behavioral responses. This facilitation is thought to
      be mediated by top-down control signals from frontal and parietal cortex that
      modulate sensory cortical activity. Here we show, using Granger causality
      measures on blood oxygen level-dependent time series, that frontal eye field
      (FEF) and intraparietal sulcus (IPS) activity predicts visual occipital activity
      before an expected visual stimulus. Top-down levels of Granger causality from FEF
      and IPS to visual occipital cortex were significantly greater than both bottom-up
      and mean cortex-wide levels in all individual subjects and the group. In the
      group and most individual subjects, Granger causality was significantly greater
      from FEF to IPS than from IPS to FEF, and significantly greater from both FEF and
      IPS to intermediate-tier than lower-tier ventral visual areas. Moreover, top-down
      Granger causality from right IPS to intermediate-tier areas was predictive of
      correct behavioral performance. These results suggest that FEF and IPS modulate
      visual occipital cortex, and FEF modulates IPS, in relation to visual attention.
      The current approach may prove advantageous for the investigation of
      interregional directed influences in other human brain functions.

PMID- 18829964
TI  - A local circuit model of learned striatal and dopamine cell responses under
      probabilistic schedules of reward.
AB  - Recently, dopamine (DA) neurons of the substantia nigra pars compacta (SNc) were
      found to exhibit sustained responses related to reward uncertainty, in addition
      to the phasic responses related to reward-prediction errors (RPEs). Thus, cue
      dependent anticipations of the timing, magnitude, and uncertainty of rewards are
      learned and reflected in components of DA signals. Here we simulate a local
      circuit model to show how learned uncertainty responses are generated, along with
      phasic RPE responses, on single trials. Both types of simulated DA responses
      exhibit the empirically observed dependencies on conditional probability,
      expected value of reward, and time since onset of the reward-predicting cue. The
      model's three major pathways compute expected values of cues, timed predictions
      of reward magnitudes, and uncertainties associated with these predictions. The
      first two pathways' computations refine those modeled by Brown et al. (1999). The
      third, newly modeled, pathway involves medium spiny projection neurons (MSPNs) of
      the striatal matrix, whose axons corelease GABA and substance P, both at synapses
      with GABAergic neurons in the substantia nigra pars reticulata (SNr) and with
      distal dendrites (in SNr) of DA neurons whose somas are located in ventral SNc.
      Corelease enables efficient computation of uncertainty responses that are a
      nonmonotonic function of the conditional probability of reward, and variability
      in striatal cholinergic transmission can explain observed individual differences
      in the amplitudes of uncertainty responses. The involvement of matricial MSPNs
      and cholinergic transmission within the striatum implies a relation between
      uncertainty in cue-reward contingencies and action-selection functions of the
      basal ganglia.

PMID- 18829965
TI  - Uncoordinated firing rate changes of striatal fast-spiking interneurons during
      behavioral task performance.
AB  - Basal ganglia circuits make key contributions to decision making. Distributed,
      synchronous feedforward inhibition of striatal medium spiny neurons by fast
      spiking GABAergic interneurons (FSIs) has been argued to be important for the
      suppression of unwanted actions, and a deficit in FSIs has been found in human
      patients with Tourette syndrome. However, no studies have yet examined how
      striatal FSIs change their activity during behavioral tasks. Here I describe 36
      presumed striatal FSIs recorded in rats during well practiced performance of a
      radial maze win-stay task. Although most FSIs showed robust task-related
      activity, the temporal patterns of firing rate change were highly idiosyncratic.
      In contrast to other classes of striatal neurons, FSIs showed little or no
      coordinated population response to major task events such as instruction cues or
      rewards. Even when multiple FSIs were recorded simultaneously from the same local
      region of striatum, firing rate changes were dissimilar, and no clear evidence
      for synchronous firing was found using cross-correlograms (18 FSI pairs
      examined). These results suggest that FSIs play a more complex role in the
      information processing achieved by striatal microcircuits than supposed by
      current theoretical models.

PMID- 18829966
TI  - The posterior parietal cortex encodes in parallel both goals for double-reach
      sequences.
AB  - The parietal reach region (PRR) is known to be involved in the preparation of
      visually guided arm movements to single targets. We explored whether PRR encodes
      only the target of the next movement or, alternatively, also a subsequent goal in
      a double-reach sequence. Two monkeys were trained to memorize the locations of
      two peripheral cues and to prepare for a memory-guided delayed double-reach
      sequence. On a GO-signal they had to reach in a predefined order to both
      remembered target locations without breaking eye fixation. The movement goals
      were arranged such that either the first or the second target was inside the
      response field of an isolated neuron. We analyzed the neural activity of single
      cells in PRR during the late memory period between cue offset and the GO-signal.
      During this memory period, most PRR cells encoded the first as well as the second
      goal of the planned reaching sequence. The results indicate that the posterior
      parietal cortex is involved in the spatial planning of more complex action
      patterns and represents immediate and subsequent movement goals.

PMID- 18829967
TI  - Dopaminergic and glutamatergic signaling crosstalk in Huntington's disease
      neurodegeneration: the role of p25/cyclin-dependent kinase 5.
AB  - Altered glutamatergic and dopaminergic signaling has been proposed as
      contributing to the specific striatal cell death observed in Huntington's disease
      (HD). However, the precise mechanisms by which mutant huntingtin sensitize
      striatal cells to dopamine and glutamate inputs remain unclear. Here, we
      demonstrate in knock-in HD striatal cells that mutant huntingtin enhances
      dopamine-mediated striatal cell death via dopamine D(1) receptors. Moreover, we
      show that NMDA receptors specifically potentiate the vulnerability of mutant
      huntingtin striatal cells to dopamine toxicity as pretreatment with NMDA
      increased D(1)R-induced cell death in mutant but not wild-type cells. As
      potential underlying mechanism of increased striatal vulnerability, we identified
      aberrant cyclin-dependent kinase 5 (Cdk5) activation. We demonstrate that
      enhanced Cdk5 phosphorylation and increased calpain-mediated conversion of the
      Cdk5 activator p35 into p25 may account for the deregulation of Cdk5 associated
      to dopamine and glutamate receptor activation in knock-in HD striatal cells.
      Moreover, supporting a detrimental role of Cdk5 in striatal cell death, neuronal
      loss can be widely prevented by roscovitine, a potent Cdk5 inhibitor.
      Significantly, reduced Cdk5 expression together with enhanced Cdk5
      phosphorylation and p25 accumulation also occurs in the striatum of mutant
      Hdh(Q111) mice and HD human brain suggesting the relevance of deregulated Cdk5
      pathway in HD pathology. These findings provide new insights into the molecular
      mechanisms underlying the selective vulnerability of striatal cells in HD and
      identify p25/Cdk5 as an important mediator of dopamine and glutamate
      neurotoxicity associated to HD.

PMID- 18829969
TI  - Perceived shape similarity among unfamiliar objects and the organization of the
      human object vision pathway.
AB  - Humans rely heavily on shape similarity among objects for object categorization
      and identification. Studies using functional magnetic resonance imaging (fMRI)
      have shown that a large region in human occipitotemporal cortex processes the
      shape of meaningful as well as unfamiliar objects. Here, we investigate whether
      the functional organization of this region as measured with fMRI is related to
      perceived shape similarity. We found that unfamiliar object classes that are
      rated as having a similar shape were associated with a very similar response
      pattern distributed across object-selective cortex, whereas object classes that
      were rated as being very different in shape were associated with a more different
      response pattern. Human observers, as well as object-selective cortex, were very
      sensitive to differences in shape features of the objects such as straight versus
      curved versus "spiky" edges, more so than to differences in overall shape
      envelope. Response patterns in retinotopic areas V1, V2, and V4 were not found to
      be related to perceived shape. The functional organization in area V3 was
      partially related to perceived shape but without a stronger sensitivity for shape
      features relative to overall shape envelope. Thus, for unfamiliar objects, the
      organization of human object-selective cortex is strongly related to perceived
      shape, and this shape-based organization emerges gradually throughout the object
      vision pathway.

PMID- 18829968
TI  - Zebrafish TRPA1 channels are required for chemosensation but not for
      thermosensation or mechanosensory hair cell function.
AB  - Transient receptor potential (TRP) ion channels have been implicated in detecting
      chemical, thermal, and mechanical stimuli in organisms ranging from mammals to
      Caenorhabditis elegans. It is well established that TRPA1 detects and mediates
      behavioral responses to chemical irritants. However, the role of TRPA1 in
      detecting thermal and mechanical stimuli is controversial. To further clarify the
      functions of TRPA1 channels in vertebrates, we analyzed their roles in zebrafish.
      The two zebrafish TRPA1 paralogs are expressed in sensory neurons and are
      activated by several chemical irritants in vitro. High-throughput behavioral
      analyses of trpa1a and trpa1b mutant larvae indicate that TRPA1b is necessary for
      behavioral responses to these chemical irritants. However, TRPA1 paralogs are not
      required for behavioral responses to temperature changes or for mechanosensory
      hair cell function in the inner ear or lateral line. These results support a role
      for zebrafish TRPA1 in chemical but not thermal or mechanical sensing, and
      establish a high-throughput system to identify genes and small molecules that
      modulate chemosensation, thermosensation, and mechanosensation.

PMID- 18829970
TI  - Control of precerebellar neuron development by Olig3 bHLH transcription factor.
AB  - The rhombic lip (RL) is the neuroepithelium immediately adjacent to the roof
      plate of the fourth ventricle, and it gives rise to various brainstem and
      cerebellar cell types. Our study shows that the bHLH (basic helix-loop-helix)
      transcription factor Olig3 is expressed in the progenitors of RL, and ablation of
      Olig3 significantly affects the development of RL. In Olig3-/- caudal RL, the
      expression level of Math1 in the dorsal interneuron 1 (dI1) domain is reduced,
      and the formation of four mossy-fiber nuclei is compromised; dI2-dI3 neurons are
      misspecified to dI4 interneurons, and the climbing-fiber neurons (inferior olive
      nucleus) are completely lost. In addition, the formation of brainstem
      (nor)adrenergic centers and first-order relay visceral sensory neurons is also
      dependent on Olig3. Therefore, Olig3 plays an important role in the fate
      specification and differentiation of caudal RL-derived neurons.

PMID- 18829972
TI  - Sleep accelerates the improvement in working memory performance.
AB  - Working memory (WM) performance, which is an important factor for determining
      problem-solving and reasoning ability, has been firmly believed to be constant.
      However, recent findings have demonstrated that WM performance has the potential
      to be improved by repetitive training. Although various skills are reported to be
      improved by sleep, the beneficial effect of sleep on WM performance has not been
      clarified. Here, we show that improvement in WM performance is facilitated by
      posttraining naturalistic sleep. A spatial variant of the n-back WM task was
      performed by 29 healthy young adults who were assigned randomly to three
      different experimental groups that had different time schedules of repetitive n
      back WM task sessions, with or without intervening sleep. Intergroup and
      intersession comparisons of WM performance (accuracy and response time) profiles
      showed that n-back accuracy after posttraining sleep was significantly improved
      compared with that after the same period of wakefulness, independent of sleep
      timing, subject's vigilance level, or circadian influences. On the other hand,
      response time was not influenced by sleep or repetitive training schedules. The
      present study indicates that improvement in n-back accuracy, which could reflect
      WM capacity, essentially benefits from posttraining sleep.

PMID- 18829971
TI  - Synchronous bursts of neuronal activity in the developing hippocampus: modulation
      by active sleep and association with emerging gamma and theta rhythms.
AB  - The neonatal hippocampus exhibits regularly recurring waves of synchronized
      neuronal activity in vitro. Because active sleep (AS), characterized by bursts of
      phasic motor activity in the form of myoclonic twitching, may provide conditions
      that are conducive to activity-dependent development of hippocampal circuits, we
      hypothesized that the waves of synchronous neuronal activity that have been
      observed in vitro would be associated with AS-related twitching. Using
      unanesthetized 1- to 12-d-old rats, we report here that the majority of neurons
      in CA1 and the dentate gyrus (DG) are significantly more active during AS than
      during either quiet sleep or wakefulness. Neuronal activity typically occurs in
      phasic bursts, during which most neurons are significantly cross-correlated both
      within and across the CA1 and DG fields. All AS-active neurons increase their
      firing rates during periods of myoclonic twitching of the limbs, and a subset of
      these neurons exhibit a burst of activity immediately after limb twitches,
      suggesting that the twitches themselves provide sensory feedback to the infant
      hippocampus, as occurs in the infant spinal cord and neocortex. Finally, the
      synchronous bursts of neuronal activity are coupled to the emergence of the AS
      related hippocampal gamma rhythm during the first postnatal week, as well as the
      emergence of the AS-related theta rhythm during the second postnatal week. We
      hypothesize that the phasic motor events of active sleep provide the developing
      hippocampus with discrete sensory stimulation that contributes to the development
      and refinement of hippocampal circuits as well as the development of synchronized
      interactions between hippocampus and neocortex.

PMID- 18829973
TI  - Spontaneous and evoked glutamate release activates two populations of NMDA
      receptors with limited overlap.
AB  - In a synapse, spontaneous and action-potential-driven neurotransmitter release is
      assumed to activate the same set of postsynaptic receptors. Here, we tested this
      assumption using (+)-5-methyl-10,11-dihydro-5H-dibenzo [a,d] cyclohepten-5,10
      imine maleate (MK-801), a well characterized use-dependent blocker of NMDA
      receptors. NMDA-receptor-mediated spontaneous miniature EPSCs (NMDA-mEPSCs) were
      substantially decreased by MK-801 within 2 min in a use-dependent manner. In
      contrast, MK-801 application at rest for 10 min did not significantly impair the
      subsequent NMDA-receptor-mediated evoked EPSCs (NMDA-eEPSCs). Brief stimulation
      in the presence of MK-801 significantly depressed evoked NMDA-eEPSCs but only
      mildly affected the spontaneous NMDA-mEPSCs detected on the same cell. Optical
      imaging of synaptic vesicle fusion showed that spontaneous and evoked release
      could occur at the same synapse albeit without correlation between their
      kinetics. In addition, modeling glutamate diffusion and NMDA receptor activation
      revealed that postsynaptic densities larger than approximately 0.2 microm(2) can
      accommodate two populations of NMDA receptors with nonoverlapping responsiveness.
      Collectively, these results support the premise that spontaneous and evoked
      neurotransmissions activate distinct sets of NMDA receptors and signal
      independently to the postsynaptic side.

PMID- 18829975
TI  - The oral multitarget tumour growth inhibitor, ZK 304709, inhibits growth of
      pancreatic neuroendocrine tumours in an orthotopic mouse model.
AB  - BACKGROUND AND AIMS: Current systemic therapies for neuroendocrine tumours (NETs)
      do not provide sufficient control of tumour growth. However, efficient evaluation
      of novel drugs is hindered by the lack of a suitable preclinical animal model.
      Here an orthotopic mouse model of pancreatic NET is established and used to study
      the action of ZK 304709, a first in class, oral multitarget tumour growth
      inhibitor. ZK 304709 is an inhibitor of cyclin-dependent kinases (Cdks) 1, 2, 4,
      7 and 9, vascular endothelial growth factor receptor-type kinases (VEGF-RTKs) 1-3
      and platelet-derived growth factor receptor-type kinase beta (PDGF-RTKss).
      METHODS: BON and QGP-1 human NET cells were used to study proliferation, survival
      and cell cycle distribution in vitro. For induction of orthotopic NETs, BON cells
      were injected into the pancreas of NMRI(nu/nu) mice. Primary tumour growth and
      metastatic spread were recorded after 9 weeks, and apoptosis, microvessel density
      and lymphatic vessel density were determined. RESULTS: ZK 304709 dose-dependently
      suppressed proliferation and colony formation of NET cells. Direct effects on NET
      cells were consistent with Cdk inhibition and involved G(2) cell cycle arrest and
      apoptosis induction, which was associated with reduced expression of MCL1
      (myeloid cell leukaemia sequence 1), survivin and hypoxia-inducible factor 1alpha
      (HIF1alpha). Apoptosis similarly occurred in vivo in ZK 304709-treated orthotopic
      BON tumours, resulting in a 80% reduction of primary tumour growth. In contrast,
      treatment with lanreotide or 5-fluorouracil and streptozotocin failed to inhibit
      tumour gowth. ZK 304709 also reduced tumour microvessel density, implicating
      antiangiogenic mechanisms. CONCLUSION: BON orthotopic tumours provide an
      informative model for preclinical drug evaluation in NETs. In this model, ZK
      304709 achieved efficacious tumour growth control via induction of apoptosis and
      inhibition of tumour-induced angiogenesis.

PMID- 18829974
TI  - Neural circuitry of stress-induced insomnia in rats.
AB  - Sleep architecture is often disturbed after a stressful event; nevertheless,
      little is known about the brain circuitry responsible for the sleep perturbations
      induced by stress. We exposed rats to a psychological stressor (cage exchange)
      that initially causes an acute stress response, but several hours later generates
      a pattern of sleep disturbances similar to that observed in stress-induced
      insomnia in humans: increased sleep latency, decreased non-REM (nREM) and REM
      sleep, increased fragmentation, and high-frequency EEG activity during nREM
      sleep. We examined the pattern of Fos expression to identify the brain circuitry
      activated, and found increased Fos in the cerebral cortex, limbic system, and
      parts of the arousal and autonomic systems. Surprisingly, there was simultaneous
      activation of the sleep-promoting areas, most likely driven by ongoing circadian
      and homeostatic pressure. The activity in the cerebral cortex and arousal system
      while sleeping generates a novel intermediate state characterized by EEG high
      frequency activity, distinctive of waking, during nREM sleep. Inactivation of
      discrete limbic and arousal regions allowed the recovery of specific sleep
      components and altered the Fos pattern, suggesting a hierarchical organization of
      limbic areas that in turn activate the arousal system and subsequently the
      cerebral cortex, generating the high-frequency activity. This high-frequency
      activity during nREM was eliminated in the stressed rats after inactivating parts
      of the arousal system. These results suggest that shutting down the residual
      activity of the limbic-arousal system might be a better approach to treat stress
      induced insomnia, rather than potentiation of the sleep system, which remains
      fully active.

PMID- 18829976
TI  - Multiple putative oncogenes at the chromosome 20q amplicon contribute to
      colorectal adenoma to carcinoma progression.
AB  - OBJECTIVE: This study aimed to identify the oncogenes at 20q involved in
      colorectal adenoma to carcinoma progression by measuring the effect of 20q gain
      on mRNA expression of genes in this amplicon. METHODS: Segmentation of DNA copy
      number changes on 20q was performed by array CGH (comparative genomic
      hybridisation) in 34 non-progressed colorectal adenomas, 41 progressed adenomas
      (ie, adenomas that present a focus of cancer) and 33 adenocarcinomas. Moreover, a
      robust analysis of altered expression of genes in these segments was performed by
      microarray analysis in 37 adenomas and 31 adenocarcinomas. Protein expression was
      evaluated by immunohistochemistry on tissue microarrays. RESULTS: The genes
      C20orf24, AURKA, RNPC1, TH1L, ADRM1, C20orf20 and TCFL5, mapping at 20q, were
      significantly overexpressed in carcinomas compared with adenomas as a consequence
      of copy number gain of 20q. CONCLUSION: This approach revealed C20orf24, AURKA,
      RNPC1, TH1L, ADRM1, C20orf20 and TCFL5 genes to be important in chromosomal
      instability-related adenoma to carcinoma progression. These genes therefore may
      serve as highly specific biomarkers for colorectal cancer with potential clinical
      applications.

PMID- 18829977
TI  - Exendin-4, a glucagon-like peptide 1 receptor agonist, protects cholangiocytes
      from apoptosis.
AB  - BACKGROUND AND AIMS: Progression of chronic cholestatic disorders towards
      ductopenia results from the dysregulation of cholangiocyte survival, with cell
      death by apoptosis prevailing over compensatory proliferation. Currently, no
      therapy is available to sustain cholangiocyte survival in the course of those
      disorders. It was recently shown that cholangiocytes express the glucagon-like
      peptide-1 receptor (GLP-1R); its activation results in enhanced proliferative
      reaction to cholestasis. The GLP-1R selective agonist exendin-4 sustains
      pancreatic beta cell proliferation and prevents cell death by apoptosis. Exendin
      4 is now employed in humans as a novel therapy for diabetes. The aim of the
      present study was to verify whether exendin-4 is effective in preventing
      cholangiocyte apoptosis. METHODS: In vitro, tests were carried out to determine
      if exendin-4 is able to prevent apoptosis of cholangiocytes isolated from normal
      rats induced by glycochenodeoxycholic acid (GCDCA); in vivo, animals subjected to
      1 week of bile duct ligation and to a single intraperitoneal injection of CCl(4)
      were treated with exendin-4 for 3 days. RESULTS: Exendin-4 prevented GCDCA
      induced Bax mitochondrial translocation, cytochrome c release and an increase in
      caspase 3 activity. Phosphatidylinositol 3-kinase, but not cAMP/protein kinase A
      or Ca(2+)/calmodulin-dependent protein kinase inhibitors, neutralised the effects
      of exendin-4. In vivo, exendin-4 administration prevented the increase in TUNEL
      (terminal deoxynucleotidyl transferase-mediated triphosphate end-labelling)
      positive cholangiocytes and the loss of bile ducts observed in bile duct-ligated
      rats treated with CCl(4). CONCLUSION: Exendin-4 prevents cholangiocyte apoptosis
      both in vitro and in vivo; such an effect is due to the ability of exendin-4 to
      counteract the activation of the mitochondrial pathway of apoptosis. These
      findings support the hypothesis that exendin-4 may be effective in slowing down
      the progression of cholangiopathies to ductopenia.

PMID- 18829978
TI  - Reducing small intestinal permeability attenuates colitis in the IL10 gene
      deficient mouse.
AB  - BACKGROUND: Defects in the small intestinal epithelial barrier have been
      associated with inflammatory bowel disease but their role in the causation of
      disease is still a matter of debate. In some models of disease increased
      permeability appears to be a very early event. The interleukin 10 (IL10) gene
      deficient mouse spontaneously develops colitis after 12 weeks of age. These mice
      have been shown to have increased small intestinal permeability that appears
      early in life. Furthermore, the development of colitis is dependent upon luminal
      agents, as animals do not develop disease if raised under germ-free conditions.
      AIMS: To determine if the elevated small bowel permeability can be prevented, and
      if by doing so colonic disease is prevented or attenuated. METHODS: IL10 gene
      deficient (IL10(-)/(-)) mice) were treated with AT-1001 (a zonulin peptide
      inhibitor), a small peptide previously demonstrated to reduce small intestinal
      permeability. Small intestinal permeability was measured, in vivo, weekly from 4
      to 17 weeks of age. Colonic disease was assessed at 8 weeks in Ussing chambers,
      and at 17 weeks of age inflammatory cytokines and myeloperoxidase were measured
      in the colon. Colonic permeability and histology were also endpoints. RESULTS:
      Treated animals showed a marked reduction in small intestinal permeability.
      Average area under the lactulose/mannitol time curve: 5.36 (SE 0.08) in controls
      vs 3.97 (SE 0.07) in the high-dose AT-1001 group, p<0.05. At 8 weeks of age there
      was a significant reduction of colonic mucosal permeability and increased
      electrical resistance. By 17 weeks of age, secretion of tumour necrosis factor
      alpha (TNFalpha) from a colonic explant was significantly lower in the treated
      group (25.33 (SE 4.30) pg/mg vs 106.93 (SE 17.51) pg/ml in controls, p<0.01). All
      other markers also demonstrated a clear reduction of colitis in the treated
      animals. Additional experiments were performed which demonstrated that AT-1001
      was functionally active only in the small intestine. CONCLUSIONS: This work
      suggests that increased intestinal permeability may be an important aetiological
      event in the development of colitis in IL10(-)/(-) mice.

PMID- 18829979
TI  - Superoxide dismutase gene transfer reduces portal pressure in CCl4 cirrhotic rats
      with portal hypertension.
AB  - BACKGROUND: Increased intrahepatic vascular tone in cirrhosis has been attributed
      to a decrease of hepatic nitric oxide (NO) secondary to disturbances in the post
      translational regulation of the enzyme eNOS. NO scavenging by superoxide (O(2)(
      )) further contributes to a reduction of NO bioavailability in cirrhotic livers.
      AIM: To investigate whether removing increased O(2)(-) levels could be a new
      therapeutic strategy to increase intrahepatic NO, improve endothelial dysfunction
      and reduce portal pressure in cirrhotic rats with portal hypertension. METHODS:
      Adenoviral vectors expressing extracellular superoxide dismutase (SOD) (AdECSOD)
      or beta-galactosidase (Adbetagal) were injected intravenously in control and
      CCl(4)-induced cirrhotic rats. After 3 days, liver O(2)(-) levels were determined
      by dihydroethidium staining, NO bioavailability by hepatic cGMP levels,
      nitrotyrosinated proteins by immunohistochemistry and western blot, and
      endothelial function by responses to acetylcholine in perfused rat livers. Mean
      arterial pressure (MAP) and portal pressure were evaluated in vivo. RESULTS:
      Transfection of cirrhotic livers with AdECSOD produced a significant reduction in
      O(2)(-) levels, a significant increase in hepatic cGMP, and a decrease in liver
      nitrotyrosinated proteins which were associated with a significant improvement in
      the endothelium-dependent vasodilatation to acetylcholine. In addition, in
      cirrhotic livers AdECSOD transfection produced a significant reduction in portal
      pressure (17.3 (SD 2) mm Hg vs 15 (SD 1.6) mm Hg; p<0.05) without significant
      changes in MAP. In control rats, AdECSOD transfection prevents the increase in
      portal perfusion pressure promoted by an ROS-generating system. CONCLUSIONS: In
      cirrhotic rats, reduction of O(2)(-) by AdECSOD increases NO bioavailability,
      improves intrahepatic endothelial function and reduces portal pressure. These
      findings suggest that scavenging of O(2)(-) might be a new therapeutic strategy
      in the management of portal hypertension.

PMID- 18829980
TI  - Sulforaphane targets pancreatic tumour-initiating cells by NF-kappaB-induced
      antiapoptotic signalling.
AB  - BACKGROUND AND AIMS: Emerging evidence suggests that highly treatment-resistant
      tumour-initiating cells (TICs) play a central role in the pathogenesis of
      pancreatic cancer. Tumour necrosis factor-related apoptosis-inducing ligand
      (TRAIL) is considered to be a novel anticancer agent; however, recent studies
      have shown that many pancreatic cancer cells are resistant to apoptosis induction
      by TRAIL due to TRAIL-activated nuclear factor-kappaB (NF-kappaB) signalling.
      Several chemopreventive agents are able to inhibit NF-kappaB, and favourable
      results have been obtained--for example, for the broccoli compound sulforaphane
      in preventing metastasis in clinical studies. The aim of the study was to
      identify TICs in pancreatic carcinoma for analysis of resistance mechanisms and
      for definition of sensitising agents. METHODS: TICs were defined by expression
      patterns of a CD44(+)/CD24(-), CD44(+)/CD24(+) or CD44(+)/CD133(+) phenotype and
      correlation to growth in immunodeficient mice, differentiation grade, clonogenic
      growth, sphere formation, aldehyde dehydrogenase (ALDH) activity and therapy
      resistance. RESULTS: Mechanistically, specific binding of transcriptionally
      active cRel-containing NF-kappaB complexes in TICs was observed. Sulforaphane
      prevented NF-kappaB binding, downregulated apoptosis inhibitors and induced
      apoptosis, together with prevention of clonogenicity. Gemcitabine, the
      chemopreventive agents resveratrol and wogonin, and the death ligand TRAIL were
      less effective. In a xenograft model, sulforaphane strongly blocked tumour growth
      and angiogenesis, while combination with TRAIL had an additive effect without
      obvious cytotoxicity in normal cells. Freshly isolated patient tumour cells
      expressing markers for TICs could be sensitised by sulforaphane for TRAIL-induced
      cytotoxicity. CONCLUSION: The data provide new insights into resistance
      mechanisms of TICs and suggest the combination of sulforaphane with TRAIL as a
      promising strategy for targeting of pancreatic TICs.

PMID- 18829981
TI  - Arabidopsis transcriptome reveals control circuits regulating redox homeostasis
      and the role of an AP2 transcription factor.
AB  - Sensors and regulatory circuits that maintain redox homeostasis play a central
      role in adjusting plant metabolism and development to changing environmental
      conditions. We report here control networks in Arabidopsis (Arabidopsis thaliana)
      that respond to photosynthetic stress. We independently subjected Arabidopsis
      leaves to two commonly used photosystem II inhibitors: high light (HL) and 3-(3,4
      dichlorophenyl)-1,1-dimethylurea (DCMU). Microarray analysis of expression
      patterns during the period of redox adjustment to these inhibitors reveals that
      20% and 8% of the transcriptome are under HL and DCMU regulation, respectively.
      Approximately 6% comprise a subset of genes common to both perturbations, the
      redox responsive genes (RRGs). A redox network was generated in an attempt to
      identify genes whose expression is tightly coordinated during adjustment to
      homeostasis, using expression of these RRGs under HL conditions. Ten subnetworks
      were identified from the network. Hierarchal subclustering of subnetworks
      responding to the DCMU stress identified novel groups of genes that were tightly
      controlled while adjusting to homeostasis. Upstream analysis of the promoters of
      the genes in these clusters revealed different motifs for each subnetwork,
      including motifs that were previously identified with responses to other
      stresses, such as light, dehydration, or abscisic acid. Functional categorization
      of RRGs demonstrated involvement of genes in many metabolic pathways, including
      several families of transcription factors, especially those in the AP2 family.
      Using a T-DNA insertion in one AP2 transcription factor (redox-responsive
      transcription factor 1 [RRTF1]) from the RRGs, we showed that the genes predicted
      to be within the subnetwork containing RRTF1 were changed in this insertion line
      (Deltarrtf1). Furthermore, Deltarrtf1 showed greater sensitivity to
      photosynthetic stress compared to the wild type.

PMID- 18829982
TI  - Catalytic key amino acids and UDP-sugar donor specificity of a plant
      glucuronosyltransferase, UGT94B1: molecular modeling substantiated by site
      specific mutagenesis and biochemical analyses.
AB  - The plant UDP-dependent glucosyltransferase (UGT) BpUGT94B1 catalyzes the
      synthesis of a glucuronosylated cyanidin-derived flavonoid in red daisy (Bellis
      perennis). The functional properties of BpUGT94B1 were investigated using protein
      modeling, site-directed mutagenesis, and analysis of the substrate specificity of
      isolated wild-type and mutated forms of BpUGT94B1. A single unique arginine
      residue (R25) positioned outside the conserved plant secondary product
      glycosyltransferase region was identified as crucial for the activity with UDP
      glucuronic acid. The mutants R25S, R25G, and R25K all exhibited only 0.5% to 2.5%
      of wild-type activity with UDP-glucuronic acid, but showed a 3-fold increase in
      activity with UDP-glucose. The model of BpUGT94B1 also enabled identification of
      key residues in the acceptor pocket. The mutations N123A and D152A decreased the
      activity with cyanidin 3-O-glucoside to less than 15% of wild type. The wild-type
      enzyme activity toward delphinidin-3-O-glucoside was only 5% to 10% of the
      activity with cyanidin 3-O-glucoside. Independent point mutations of three
      residues positioned near the acceptor B ring were introduced to increase the
      activity toward delphinidin-3-O-glucoside. In all three mutant enzymes, the
      enzymatic activity toward both acceptors was reduced to less than 15% of wild
      type. The model of BpUGT94B1 allowed for correct identification of catalytically
      important residues, within as well as outside the plant secondary product
      glycosyltransferase motif, determining sugar donor and acceptor specificity.

PMID- 18829983
TI  - Cell membrane surface potential (psi0) plays a dominant role in the phytotoxicity
      of copper and arsenate.
AB  - Negative charges at cell membrane surfaces (CMS) create a surface electrical
      potential (psi(0)) that affects ion concentrations at the CMS and consequently
      affects the phytotoxicity of metallic cations and metalloid anions in different
      ways. The zeta potentials of root protoplasts of wheat (Triticum aestivum), as
      affected by the ionic environment of the solution, were measured and compared
      with the values of psi(0) calculated with a Gouy-Chapman-Stern model. The
      mechanisms for the effects of cations (H(+), Ca(2+), Mg(2+), Na(+), and K(+)) on
      the acute toxicity of Cu(2+) and As(V) to wheat were studied in terms of psi(0).
      The order of effectiveness of the ions in reducing the negativity of psi(0) was
      H(+) > Ca(2+) approximately Mg(2+) > Na(+) approximately K(+). The calculated
      values of psi(0) were proportional to the measured zeta potentials (r(2) = 0.93).
      Increasing Ca(2+) or Mg(2+) activities in bulk-phase media resulted in decreased
      CMS activities of Cu(2+) ({Cu(2+)}(0)) and increased CMS activities of As(V)
      ({As(V)}(0)). The 48-h EA50{Cu(2+)}(b) ({Cu(2+)} in bulk-phase media accounting
      for 50% inhibition of root elongation over 48 h) increased initially and then
      declined, whereas the 48-h EA50{As(V)}(b) decreased linearly. However, the
      intrinsic toxicity of Cu(2+) (toxicity expressed in terms of {Cu(2+)}(0))
      appeared to be enhanced as psi(0) became less negative and the intrinsic toxicity
      of As(V) appeared to be reduced. The psi(0) effects, rather than site-specific
      competitions among ions at the CMS (invoked by the biotic ligand model), may play
      the dominant role in the phytotoxicities of Cu(2+) and As(V) to wheat.

PMID- 18829984
TI  - Decreased expression of cytosolic pyruvate kinase in potato tubers leads to a
      decline in pyruvate resulting in an in vivo repression of the alternative
      oxidase.
AB  - The aim of this work was to investigate the effect of decreased cytosolic
      pyruvate kinase (PKc) on potato (Solanum tuberosum) tuber metabolism. Transgenic
      potato plants with strongly reduced levels of PKc were generated by RNA
      interference gene silencing under the control of a tuber-specific promoter.
      Metabolite profiling showed that decreased PKc activity led to a decrease in the
      levels of pyruvate and some other organic acids involved in the tricarboxylic
      acid cycle. Flux analysis showed that this was accompanied by changes in carbon
      partitioning, with carbon flux being diverted from glycolysis toward starch
      synthesis. However, this metabolic shift was relatively small and hence did not
      result in enhanced starch levels in the tubers. Although total respiration rates
      and the ATP to ADP ratio were largely unchanged, transgenic tubers showed a
      strong decrease in the levels of alternative oxidase (AOX) protein and a
      corresponding decrease in the capacity of the alternative pathway of respiration.
      External feeding of pyruvate to tuber tissue or isolated mitochondria resulted in
      activation of the AOX pathway, both in the wild type and the PKc transgenic
      lines, providing direct evidence for the regulation of AOX by changes in pyruvate
      levels. Overall, these results provide evidence for a crucial role of PKc in the
      regulation of pyruvate levels as well as the level of the AOX in heterotrophic
      plant tissue, and furthermore reveal that these parameters are interlinked in
      vivo.

PMID- 18829985
TI  - The transcript and metabolite networks affected by the two clades of Arabidopsis
      glucosinolate biosynthesis regulators.
AB  - In this study, transcriptomics and metabolomics data were integrated in order to
      examine the regulation of glucosinolate (GS) biosynthesis in Arabidopsis
      (Arabidopsis thaliana) and its interface with pathways of primary metabolism. Our
      genetic material for analyses were transgenic plants overexpressing members of
      two clades of genes (ALTERED TRYPTOPHAN REGULATION1 [ATR1]-like and MYB28-like)
      that regulate the aliphatic and indole GS biosynthetic pathways (AGs and IGs,
      respectively). We show that activity of these regulators is not restricted to the
      metabolic space surrounding GS biosynthesis but is tightly linked to more distal
      metabolic networks of primary metabolism. This suggests that with similarity to
      the regulators we have investigated here, other factors controlling pathways of
      secondary metabolism might also control core pathways of central metabolism. The
      relatively broad view of transcripts and metabolites altered in transgenic plants
      overexpressing the different factors underlined novel links of GS metabolism to
      additional metabolic pathways, including those of jasmonic acid, folate, benzoic
      acid, and various phenylpropanoids. It also revealed transcriptional and
      metabolic hubs in the "distal" network of metabolic pathways supplying precursors
      to GS biosynthesis and that overexpression of the ATR1-like clade genes has a
      much broader effect on the metabolism of indolic compounds than described
      previously. While the reciprocal, negative cross talk between the methionine and
      tryptophan pathways that generate GSs in Arabidopsis has been suggested
      previously, we now show that it is not restricted to AGs and IGs but includes
      additional metabolites, such as the phytoalexin camalexin. Combining the
      profiling data of transgenic lines with gene expression correlation analysis
      allowed us to propose a model of how the balance in the metabolic network is
      maintained by the GS biosynthesis regulators. It appears that ATR1/MYB34 is an
      important mediator between the gene activities of the two clades. While it is
      very similar to the ATR1-like clade members in terms of downstream gene targets,
      its expression is highly correlated with that of the MYB28-like clade members.
      Finally, we used the unique transgenic plants obtained here to show that AGs are
      likely more potent deterrents of the whitefly Bemisia tabaci compared with IGs.
      The influence on insect behavior raises an important question for future
      investigation of the functional aspect of our initial finding, which pointed to
      enriched expression of the MYB28-like clade genes in the abaxial domain of the
      Arabidopsis leaf.

PMID- 18829986
TI  - Methylation of CIITA promoter IV causes loss of HLA-II inducibility by IFN-gamma
      in promyelocytic cells.
AB  - The human promyelocytic cell line THP-1 expresses high level of HLA class II (HLA
      II) molecules after IFN-gamma treatment. Here, we report a variant of THP-1 that
      does not express HLA-II after IFN-gamma. The variant's HLA-II phenotype is
      constant over time in culture and it is not related to a defective IFN-gamma
      signalling pathway. Transfection of CIITA, the HLA-II transcriptional activator,
      under the control of a cytomegalovirus promoter rescues high level of HLA-DR
      surface expression in the variant indicating that the biosynthetic block resides
      in the expression of CIITA and not in the CIITA-dependent transactivation of the
      HLA-II promoters. Treatment of the variant with 5-azacytidine (5-aza), which
      inhibits CpG methylation, restores inducibility of HLA-II by IFN-gamma both at
      transcriptional and phenotypic level and antigen presenting and processing
      function of the variant. DNA studies demonstrate that the molecular defect of the
      THP-1 variant originates from the methylation of the CIITA promoter IV.
      Furthermore, treatment with 5-aza produces a substantial demethylation of CIITA
      promoter IV and a significant increase of IFN-gamma-dependent HLA-II expression
      in another myelomonocytic cell line, U937. Therefore hyper-methylation of CIITA
      promoter IV may be a relevant mechanism of epigenetic control preventing HLA-II
      IFN-gamma inducibility in the myelomonocytic cell lineage.

PMID- 18829987
TI  - CD28 stimulation triggers NF-kappaB activation through the CARMA1-PKCtheta
      Grb2/Gads axis.
AB  - CD28 stimulation contributes to activation of the IL-2 promoter by up-regulating
      the activity of several transcription factors, including nuclear factor kappaB
      (NF-kappaB)/Rel family members. However, the signal-transducing cascades linking
      the CD28 molecule and activation of NF-kappaB remain unclear. Protein kinase C
      (PKC) , CARMA1 and Bcl10 have recently been reported to integrate TCR-mediated NF
      kappaB activation. However, since the data in these studies were drawn from
      experiments in which T cells were usually stimulated with both TCR and CD28, the
      relative contributions of TCR- and CD28-mediated signals to initiation of the NF
      kappaB pathway remain elusive. To examine the role of these molecules in NF
      kappaB activation through CD28-mediated stimulation, Bcl10 was over-expressed in
      Jurkat cells and their NF-kappaB activation by CD28- or TCR-cross-linking was
      evaluated. We found that CD28 stimulation alone can induce NF-kappaB activation
      in Bcl10-over-expressing Jurkat cells, whereas TCR stimulation alone has only
      little effect. In addition, we found that Bcl10-induced NF-kappaB activation
      through CD28-mediated stimulation could be blocked by the dominant-negative form
      of PKC or CARMA1. Furthermore, genetic studies revealed that Grb2/Gads binding,
      but not phosphatidylinositol 3-kinase binding, is important in CD28-mediated NF
      kappaB activation. These findings indicate that the PKC-CARMA1-Bcl10 signaling
      pathway participates in the CD28 co-stimulatory signal independently of the TCR
      signaling pathway, which leads us to propose that the activation of the NF-kappaB
      signaling pathway via PKC-CARMA1-Bcl10 may be markedly dependent on CD28
      stimulation rather than TCR stimulation.

PMID- 18829988
TI  - Vessel shrinkage as a sign of atherosclerosis progression in type 2 diabetes: a
      serial intravascular ultrasound analysis.
AB  - OBJECTIVE: The aim of this study was to determine the natural history of vascular
      remodeling of atherosclerotic plaques in patients with type 2 diabetes and the
      predictors of vessel shrinkage. RESEARCH DESIGN AND METHODS: In this serial
      intracoronary ultrasound (IVUS) study, 237 coronary segments from 45 patients
      enrolled in the DIABETES I, II, and III trials were included. Quantitative
      volumetric IVUS analyses (motorized pullbacks at 0.5 mm/s) were performed in the
      same coronary segment after the index procedure and at the 9-month follow-up.
      Nontreated mild lesions (angiographic stenosis <25%) with > or =0.5 mm plaque
      thickening and length of > or =5 mm assessed by IVUS were included. Vessel
      shrinkage was defined as a Deltaexternal elastic membrane area/Deltaplaque area <
      0. Statistical adjustment by multiple segments and multiple lesions per patient
      was performed. RESULTS: Vessel shrinkage was identified in 37.1% of segments and
      was associated with a significant decrease in lumen area at 9 months (vessel
      shrinkage, 10 +/- 4 mm(2) vs. non-vessel shrinkage, 11 +/- 4 mm(2); P = 0.04).
      Independent predictors of vessel shrinkage were insulin requirements (odds ratio
      4.6 [95% CI 1.40-15.10]; P = 0.01), glycated hemoglobin (1.5 [1.05-2.10]; P =
      0.02), apolipoprotein B (0.96 [0.94-0.98]; P < 0.001), hypertension (3.7 [1.40
      10.30]; P = 0.009), number of diseased vessels (5.6 [2.50-12.50]; P < 0.001), and
      prior revascularization (17.5 [6.50-46.90]; P < 0.001). CONCLUSIONS: This serial
      IVUS study suggests that progression of coronary artery disease in patients with
      type 2 diabetes may be mainly attributed to vessel shrinkage. Besides, vessel
      shrinkage is influenced by insulin requirements and metabolic control and is
      associated with more advanced coronary atherosclerosis.

PMID- 18829989
TI  - Phenotypic switching of adipose tissue macrophages with obesity is generated by
      spatiotemporal differences in macrophage subtypes.
AB  - OBJECTIVE: To establish the mechanism of the phenotypic switch of adipose tissue
      macrophages (ATMs) from an alternatively activated (M2a) to a classically
      activated (M1) phenotype with obesity. RESEARCH DESIGN AND METHODS: ATMs from
      lean and obese (high-fat diet-fed) C57Bl/6 mice were analyzed by a combination of
      flow cytometry, immunofluorescence, and expression analysis for M2a and M1 genes.
      Pulse labeling of ATMs with PKH26 assessed the recruitment rate of ATMs to
      spatially distinct regions. RESULTS: Resident ATMs in lean mice express the M2a
      marker macrophage galactose N-acetyl-galactosamine specific lectin 1 (MGL1) and
      localize to interstitial spaces between adipocytes independent of CCR2 and CCL2.
      With diet-induced obesity, MGL1(+) ATMs remain in interstitial spaces, whereas a
      population of MGL1(-)CCR2(+) ATMs with high M1 and low M2a gene expression is
      recruited to clusters surrounding necrotic adipocytes. Pulse labeling showed that
      the rate of recruitment of new macrophages to MGL1(-) ATM clusters is
      significantly faster than that of interstitial MGL1(+) ATMs. This recruitment is
      attenuated in Ccr2(-/-) mice. M2a- and M1-polarized macrophages produced
      different effects on adipogenesis and adipocyte insulin sensitivity in vitro.
      CONCLUSIONS: The shift in the M2a/M1 ATM balance is generated by spatial and
      temporal differences in the recruitment of distinct ATM subtypes. The obesity
      induced switch in ATM activation state is coupled to the localized recruitment of
      an inflammatory ATM subtype to macrophage clusters from the circulation and not
      to the conversion of resident M2a macrophages to M1 ATMs in situ.

PMID- 18829990
TI  - Intracellular angiotensin II production in diabetic rats is correlated with
      cardiomyocyte apoptosis, oxidative stress, and cardiac fibrosis.
AB  - OBJECTIVE: Many of the effects of angiotensin (Ang) II are mediated through
      specific plasma membrane receptors. However, Ang II also elicits biological
      effects from the interior of the cell (intracrine), some of which are not
      inhibited by Ang receptor blockers (ARBs). Recent in vitro studies have
      identified high glucose as a potent stimulus for the intracellular synthesis of
      Ang II, the production of which is mainly chymase dependent. In the present
      study, we determined whether hyperglycemia activates the cardiac intracellular
      renin-Ang system (RAS) in vivo and whether ARBs, ACE, or renin inhibitors block
      synthesis and effects of intracellular Ang II (iAng II). RESEARCH DESIGN AND
      METHODS: Diabetes was induced in adult male rats by streptozotocin. Diabetic rats
      were treated with insulin, candesartan (ARB), benazepril (ACE inhibitor), or
      aliskiren (renin inhibitor). RESULTS: One week of diabetes significantly
      increased iAng II levels in cardiac myocytes, which were not normalized by
      candesartan, suggesting that Ang II was synthesized intracellularly, not
      internalized through AT(1) receptor. Increased intracellular levels of Ang II,
      angiotensinogen, and renin were observed by confocal microscopy. iAng II
      synthesis was blocked by aliskiren but not by benazepril. Diabetes-induced
      superoxide production and cardiac fibrosis were partially inhibited by
      candesartan and benazepril, whereas aliskiren produced complete inhibition.
      Myocyte apoptosis was partially inhibited by all three agents. CONCLUSIONS:
      Diabetes activates the cardiac intracellular RAS, which increases oxidative
      stress and cardiac fibrosis. Renin inhibition has a more pronounced effect than
      ARBs and ACE inhibitors on these diabetes complications and may be clinically
      more efficacious.

PMID- 18829991
TI  - Late outcomes after drug-eluting stent implantation in "real-world" clinical
      practice.
AB  - BACKGROUND: We report the late outcomes in 411 consecutive patients undergoing
      drug-eluting stent (DES) implantation by a single operator between 2003-2006.
      METHODS: Prospective registry with continuous follow up. Patients with stable
      angina (SA) or acute coronary syndrome (ACS) received DES for long lesions, small
      vessels, chronic total occlusion, bifurcation, aorto-ostial, left main, post
      atherectomy or saphenous vein graft lesions, multivessel/multilesion single
      vessel (V) disease, in-stent restenosis (ISR) or diabetes. RESULTS: Age range: 34
      86 years. One hundred sixty-six (40.3%) had ACS, 98.3% hypercholesterolemia and
      14.6% diabetes. Two hundred sixty-one (63.5%) had percutaneous coronary
      intervention (PCI) to 1V and 150 (36.5%) to >1V. Six hundred seven V were
      treated. Two hundred fifty-nine patients (63%) had multilesion PCI, and 109
      (26.5%) 1V multilesion PCI. Two hundred ninety-three (71.3%) patients had long
      lesions and 224 had Vs < 2.75 mm diameter. 75.5% of lesions were Type B2/C. 1-8
      stents were implanted/patient. Eight hundred twenty-two of 883 stents were DES.
      One hundred eight patients received > or = 1 stent of < or = 2.5 mm diameter and
      246 patients received stents greater than or equal to 20 mm long. Twenty-five
      patients developed late complications. ISR occurred in 23, 3.5-38 months after
      DES implantation. Three had sudden late DES thrombosis (LST). One-third also had
      ISR. Twenty of twenty-five required PCI, 1 CABG and 4 medical treatment.
      Subsequently, 3 of the 20 required further PCI for recurrent ISR and 1 CABG. 9
      patients died during 1-5-year follow up. CONCLUSIONS: In "real-world" patients at
      increased risk of ISR after bare-metal stenting (BMS), "off-label" DES
      implantation has a low incidence of late complications. The most common is ISR
      which presents later than after BMS. Acute LST is serious but unusual and may be
      accompanied by ISR.

PMID- 18829992
TI  - Outcomes of DES in real-world practice: realizing the potential.

PMID- 18829993
TI  - Unprotected left main coronary artery bifurcation stenosis: impact of plaque
      debulking prior to single sirolimus-eluting stent implantation.
AB  - BACKGROUND: The impact of plaque debulking with directional coronary atherectomy
      (DCA) prior to single sirolimus-eluting stent (SES) implantation in an
      unprotected left main coronary artery (LMCA) involving bifurcation stenosis has
      not been fully evaluated. METHODS: One hundred and one patients with unprotected
      LMCA bifurcation lesions treated with single SES implantation (from the LMCA to
      the left descending coronary artery [LAD] across the left circumflex artery [LCx]
      ostium) were divided into 2 groups: DCA group (n = 41, plaque debulking with DCA
      prior to SES implantation) and non-DCA group (n = 60, single SES implantation
      alone). Clinical outcomes as well as angiographic data at baseline, post
      procedure and follow up were compared between the two groups. RESULTS: At 1-year
      follow up, freedom from major adverse cardiac events was 97.4 +/- 2.6% in the DCA
      group, and 88.6 +/- 4.4% in the non-DCA group (p = 0.129). Baseline quantitative
      coronary angiographic analyses revealed that the percent diameter stenosis (%DS)
      of the LCx was higher in the DCA group than in the non-DCA group (36.8 +/- 21.5%
      vs. 26.9 +/- 19.2%; p = 0.029). Moreover, the %DS of the LCx after PCI and at 9
      month follow up was lower in the DCA group (19.2 +/- 13.1% vs. 28.3 +/- 22.7%; p
      = 0.034; 20.8 +/- 12.3% vs. 31.9 +/- 21.4%; p = 0.007, respectively).
      Furthermore, restenosis at the LCx ostium was not observed in the DCA group, but
      was seen in 5 cases in the non-DCA group (0% vs. 10.2%; p = 0.048). CONCLUSION:
      Plaque debulking with DCA prior to single SES implantation effectively reduced
      restenosis of the LCx ostium in this challenging lesion subset.

PMID- 18829994
TI  - Coronary stenting with MGuard: first-in-man trial.
AB  - MGuard is a bare-metal stent covered by an ultrathin polymer mesh sleeve on its
      external surface, designed to reduce embolization during coronary,
      cerebrovascular and peripheral interventions. AIM: To evaluate the feasibility
      and safety of MGuard-based percutaneous coronary interventions (PCIs) of human
      native coronary arteries (NCs) and coronary vein grafts (VGs). METHODS: MGuard
      based PCI executed by 2 centers with postprocedural clinical and laboratory
      monitoring; including creatinine phosphokinase (CPK), troponin,
      electrocardiography and 6-month angiographic follow up. The primary endpoint was
      30-day major adverse cardiac events (MACE) including cardiac death, myocardial
      infarction, stent thrombosis and repeat target lesion revascularization. The
      secondary endpoint was device and procedural success. RESULTS: Twenty-nine
      patients with a mean age of 68.1 +/- 12 years were enrolled. The mean VG age (n =
      17) was 12.6 years (range 8-19). All patients received heparin, clopidogrel and
      aspirin, while none received bivalirudin, glycoprotein IIb/IIIa inhibitors (GPIs)
      or an embolic protection device (EPD). Device and procedural success were 100%
      and 96.5%, respectively. One patient experienced a procedure-related CPK rise. No
      MACE were reported at 1 month. CONCLUSION: MGuard-based PCI of NCs and VGs
      appears encouraging, especially in view of unfavorable patient and lesion
      characteristics. Both efficacy and safety need to be further established in
      larger-scale studies with longer follow-up periods.

PMID- 18829995
TI  - Treatment of bifurcation lesions using dedicated bifurcation stents versus
      classic bare-metal stents. Randomized, controlled trial with 12-month
      angiographic follow up.
AB  - BACKGROUND: The aim of this study was to compare the use of classic bare- metal
      stents with dedicated bifurcation bare-metal stents in patients who were not
      eligible for drug-eluting stents (DES) implantation. METHODS: Sixty patients with
      bifurcation stenosis were randomly assigned to received either a dedicated
      bifurcation or a bare-metal stent (n = 30) or classic bare-metal stent (n = 30)
      with stenting of the parent vessel and angioplasty/or provisional stenting of the
      side branch. Fifty-nine patients underwent 12-month clinical and angiographic
      follow up unless this was performed earlier due to symptoms. Dual antiplatelet
      treatment was administered for 1 month. Acute success as well as the long-term
      clinical and angiographic outcome have been assessed in both groups. RESULTS:
      Baseline demographic, angiographic and procedure-related characteristics were
      well balanced in both groups. The use of dedicated stents was associated either
      with reduced procedure or fluoroscopy time (34 +/- 9 minutes vs. 46 +/- 20
      minutes; p = 0.004 and 9 +/- 6 minutes vs. 15 +/- 9 minutes; p = 0.003,
      respectively) and lesser contrast volume (168 +/- 86 milliliters vs. 199 +/- 103
      ml; p = 0.02). At the 12-month follow up, no statistically significant difference
      was found between both groups regarding major adverse cardiovascular events
      (MACE) (13.7 vs. 13.3%; p = 0.9). CONCLUSIONS: In our study we failed to
      demonstrate the superiority of a dedicated stent versus classic a bare-metal
      stent for the treatment of bifurcation lesions regarding MACE in patients who
      were not eligible for DES implantation. However, the use of dedicated stents may
      be preferable due to reduced procedure and fluoroscopy time and lesser contrast
      volume.

PMID- 18829996
TI  - Comparison of Inoue balloon, metallic commissurotome and multi-track double
      balloon valvuloplasty in the treatment of rheumatic mitral stenosis.
AB  - BACKGROUND Percutaneous mitral valvuloplasty (PMV) is a well known non-surgical
      technique for treating patients with rheumatic mitral stenosis (MS). There are
      very few studies that have compared the 3 techniques together for their safety
      and efficacy. METHODS: To compare the three different techniques for percutaneous
      mitral valvuloplasty (PMV) using Inoue balloon (IB), metallic commissurotome
      (PMMC), or multi-track double balloon (MTDB) in patients with MS. RESULTS: A
      total of 486 patients were subjected to PMV using any of the 3 techniques, IB,
      PMMC or MTDB. The overall success rate was 97.3% (n = 473); 95.7% for IB, 97.6%
      for PMMC, and 98.3% for MTDB. Overall, the transmitral gradient decreased from
      20.7 +/- 7.2 mmHg to 6.5 +/- 3.7 mmHg (p < 0.001) and mitral valve area (MVA)
      increased from 0.87 +/- 0.2 cm(2) to 1.9 +/- 0.4 cm(2) (p < 0.001). Left atrial
      pressure decreased from 29.3 +/- 8.4 mmHg to 16.1 +/- 11.5 mmHg (p < 0.001) and
      pulmonary arterial pressure decreased from 76.9 +/- 41.8 mmHg to 45.2 +/- 17.6
      mmHg (p < 0.001). Thirteen patients (2.7%) required mitral valve replacement
      (MVR) for severe mitral regurgitation (MR) while one patient (0.2%) developed
      cardiac tamponade requiring urgent pericardiocentesis followed by surgical repair
      of the tear and open mitral valvotomy. There was no statistical difference among
      the 3 techniques used. CONCLUSION: In conclusion, percutaneous mitral
      valvuloplasty is an effective procedure for MS with any of the three above
      techniques.

PMID- 18829997
TI  - Hydration protocols to reduce the incidence of contrast-induced nephropathy.

PMID- 18829999
TI  - Magnesium sulfate for transradial cardiac catheterization: teaching an old dog
      new tricks.

PMID- 18829998
TI  - Magnesium sulphate during transradial cardiac catheterization: a new use for an
      old drug?
AB  - OBJECTIVE: To assess the effect of intra-arterial magnesium on the radial artery
      during transradial cardiac catheterization. BACKGROUND: Transradial coronary
      angiography has become popular in the last decade and offers several advantages
      over transfemoral angiography. Radial artery spasm is a major limitation of this
      approach, and a vasodilatory cocktail is usually given. The aim of this study was
      to examine the effect of magnesium sulphate on the radial artery during cardiac
      catheterization. METHODS: This was a prospective, double-blind, randomized trial
      of 86 patients undergoing radial catheterization. Patients were randomized to
      receive magnesium sulphate (150 mg) or verapamil (1 mg) into the radial sheath.
      Radial dimensions were assessed using Doppler ultrasound. The primary endpoint of
      the study was a change in radial artery diameter following administration.
      Secondary endpoints included operator-defined radial artery spasm and patient
      pain. RESULTS: Following administration of the study drug, there was an increase
      in radial artery diameter in both groups (p < 0.01), although the increase seen
      was greater in the group receiving magnesium (magnesium 0.36 +/- 0.03 mm;
      verapamil 0.27 +/- 0.03 mm; p < 0.05). Administration of verapamil resulted in a
      fall in mean arterial pressure (MAP) (change in MAP -6.6 +/- 1.4 mmHg; p < 0.01),
      whereas magnesium did not have a hemodynamic effect. Severe arm pain (pain score
      > 5) was observed in 14 (30%) patients receiving verapamil and 9 (27%) receiving
      magnesium (p = NS). CONCLUSION: This study demonstrates that magnesium is a more
      effective vasodilator when compared to verapamil, with a reduced hemodynamic
      effect, and is equally effective at preventing radial artery spasm. As such, the
      use of this agent offers distinct advantages over verapamil during radial
      catheterization.

PMID- 18830000
TI  - Transradial retrieval of a dislodged stent from the left main coronary artery.
AB  - We report a case of successful transradial retrieval of a dislodged and
      mechanically distorted coronary artery stent from the left main stem in an
      elderly male. Transradial percutaneous coronary intervention was undertaken to
      reconstruct a lesion in the left circumflex artery complicated by stent
      dislodgement. A microsnare was used to successfully retrieve the stent.

PMID- 18830001
TI  - Radial access - be prepared!
AB  - We present the case of a 46-year-old female patient that experienced recurrent
      stent thrombosis and underwent attempted primary PCI via the radial artery.
      Although radial artery cannulation with a 6 Fr sheath and the diagnostic
      angiography were successfully performed, the PCI could not be achieved because of
      failure to advance the 6 Fr guide through the radial artery, due to severe
      angulation of a high take-off radial artery, combined with a proximal radial
      artery stenosis.

PMID- 18830002
TI  - Use of intra-arterial papaverine for severe arterial spasm during radial cardiac
      catheterization.
AB  - Coronary angiography and intervention can be performed safely using the radial
      artery. However, arterial spasm is often encountered and usually amenable to
      nitrate/verapamil therapy. Rarely, surgical intervention is required to remove
      catheters and wires. Intra-arterial papavarine can be used to treat severe radial
      artery spasm and prevent the need for urgent surgical intervention.

PMID- 18830003
TI  - Spontaneous coronary artery dissection: case series and review.
AB  - Spontaneous coronary artery dissection (SCAD) is a rare but important cause of
      acute coronary syndromes. SCAD can cause unstable angina, acute myocardial
      infarction, and sudden death. Predisposing factors include atherosclerosis, the
      peripartum period, and structural and inflammatory conditions affecting the
      arterial wall. The diagnosis of coronary dissection is usually made by coronary
      angiography. Prompt diagnosis and treatment of patients with dissection improves
      survival. Therapeutic options include medical therapy, percutaneous coronary
      intervention, and surgery. We present a series of patients with spontaneous
      coronary artery dissection at our institution. The etiology, pathogenesis,
      diagnosis, treatment, and prognosis of patients with coronary dissection are
      reviewed.

PMID- 18830004
TI  - Vascular changes and black hole phenomenon after coronary brachytherapy: a
      pathologically distinct entity.
AB  - Restenosis remains an important issue even after coronary brachytherapy despite
      its efficacy in the treatment for in-stent restenosis. The acute and chronic
      changes in vascular wall are unique following brachytherapy. The restenotic
      tissue post coronary brachytherapy is relatively acellular and appears echolucent
      in intravascular ultrasound examination. This is dubbed the "black hole"
      phenomenon. Despite the similarity in the mode of action of brachytherapy and
      drug eluting stent implantation, the black hole phenomenon seems to be uncommon
      after drug-eluting stent implantation except in those patients who have had prior
      brachytherapy, bare-metal placement and after treatment of saphenous venous graft
      stenosis. It is possible that not all neointima in stents are created equal. We
      should propose that neointima be considered primary neointima if it forms after
      bare metal stenting, secondary neointima if it forms after CBT or DES, and
      perhaps tertiary if after combined CBT and DES. This type of classification may
      prove useful for research or clinical purposes. Almost certainly black hole
      phenomenon results from a modified neointima. However, we do not know whether
      this is the same restenotic tissue that was present before CBT but just depleted
      of its cellular element secondary to autolysis or a newly formed tertiary
      neointima? It is also not clear whether the changes in vascular wall and
      restenosis are similar after CBT or drug-eluting stent placement. However, there
      are some unique vascular changes that seem to be common after both of these
      procedures.

PMID- 18830005
TI  - Late presentation of an anomalous origin of the left coronary artery from the
      pulmonary artery: case report and review.
AB  - Anomalous origin of the left coronary artery (LCA) from the pulmonary artery
      (ALCAPA) is a rare cause of ischemia, heart failure and/or sudden death. A
      premortem diagnosis beyond early childhood is exceedingly rare because over 90%
      of untreated infants die in the first 12 months of life. We present a case of an
      asymptomatic fourteen-year old male with ALCAPA diagnosed by multidetector
      computed tomography (MDCT) angiography, who was successfully treated by surgical
      coronary transfer of the ALCAPA with reimplantation of the LCA to the aortic
      root.

PMID- 18830006
TI  - Percutaneous mitral valvuloplasty through a Carpentier-Edwards ring.
AB  - The authors report the case of a young girl with a Carpentier-Edwards
      annuloplasty ring for severe rheumatic mitral disease who presented 4 years later
      with mitral restenosis due to commissural fusion. She underwent successful
      percutaneous mitral commissurotomy with an Inoue balloon. Technical specificities
      and the safety of the procedure are briefly discussed.

PMID- 18830007
TI  - Three cases of left main stem thrombus complicating PCI: the role of FilterWire
      protection for the virgin territory.
AB  - We report on three cases of left main stem thrombosis complicating percutaneous
      coronary angioplasty. We focused on the issue of dealing with emboli in the non
      culprit vessel, as embolism in the "virgin" vessel is often associated with
      severe cardiogenic shock. We describe the use of a FilterWire technique to
      protect the non-culprit vessel and a case in which the FilterWire was occluded by
      thrombus leading to shock. The third case illustrates the difficulty with
      FilterWire protection if stenting is required in the left main stem itself.

PMID- 18830008
TI  - Covered stent for the treatment of recurrent bilateral renal artery in-stent
      restenosis.
AB  - The optimal treatment for renal artery in-stent restenosis (ISR) is not well
      established. Reintervention with different strategies including balloon
      angioplasty, cutting-balloon angioplasty, additional stenting with bare-metal,
      drug-eluting or covered stents and brachytherapy are effective in achieving
      immediate angiographic success. However, recurrent ISR rates are high
      irrespective of treatment strategy. We present a case describing the use of a
      covered stent for the treatment of recurrent bilateral renal artery ISR after
      bare-metal and drug-eluting stent implantation and cutting-balloon angioplasty.

PMID- 18830009
TI  - Percutaneous repair of a pseudoaneurysm associated with coarctation of the aorta.
AB  - Children with congenital heart disease represent 1% of live births, and it is
      estimated that millions will reach adulthood. Advances in cardiac surgery for the
      treatment of pediatric congenital heart disease have allowed many of these
      patients to enjoy a long life. Adults with a history of repaired congenital heart
      disease present different and unique challenges to the adult interventional
      cardiologist. This is a case report of a patient who presented with
      pseudoaneurysm of a repaired coarctation of the aorta, illustrating the need for
      the interventional cardiologist to be innovative in using the many occluding
      devices available in the laboratory. Our case demonstrates the technical
      feasibility of occluding the pseudoaneurysm tube graft used for the correction of
      the coarctation of the aorta. This procedure can be performed safely and
      successfully in expert hands.

PMID- 18830010
TI  - Spontaneous hemopericardium in a patient with hemophilia B: a case report and
      review of the literature.
AB  - Spontaneous hemopericardium is extremely rare in patients with hemophilia and has
      never been reported in hemophilia B-factor IX deficiency. We report a patient
      with hemophilia B who presented with spontaneous hemopericardium and tamponade
      requiring emergent pericardiocentesis. As advances in therapies improve the
      longevity and quality of life of patients with hemophilia, it is likely that
      adult interventional cardiologists will increasingly encounter these patients in
      the cardiac catheterization laboratory. We review the clinical challenges raised
      by this group of patients undergoing cardiac procedures and present a stepwise
      approach to optimal management during the periprocedural period.

PMID- 18830011
TI  - An uncommon complication after a common procedure.
AB  - A 50-year-old female developed cortical blindness 5 hours after coronary
      angiography. A non-contrast-enhanced computed tomographic scan of the brain
      revealed bilateral occipital and middle cerebral/posterior cerebral artery
      watershed territory infarcts with a possibility of subarachnoid hemorrhage (SAH).
      Magnetic resonance imaging of the brain revealed the above infarcts, but not SAH.
      The selective vulnerability of occipital lobes to contrast agent toxicity was
      postulated as the underlying mechanism. The patient had partial recovery of
      vision.

PMID- 18830012
TI  - Intracoronary thrombus aspiration through a guiding catheter in a case with stent
      thrombosis.
AB  - A 50-year-old male with a history of inferior myocardial infarction and stent
      implantation to the right coronary artery 20 days prior this admission presented
      with acute inferior myocardial re-infarction. Diagnostic right coronary
      angiography revealed a massive thrombus within the previously implanted stent.
      After manual aspiration through a guiding catheter, a large, fresh thrombus was
      removed. Subsequently, thrombolysis in myocardial infarction (TIMI) 3 flow was
      established, and no further intervention was required. The patient was discharged
      uneventfully on medical therapy.

PMID- 18830013
TI  - Introduction: Novel approaches to managing bradycardia during coronary rheolytic
      thrombectomy.

PMID- 18830014
TI  - The potential mechanisms of bradyarrhythmias associated with AngioJet
      thrombectomy.
AB  - The AngioJet Rheolytic Thrombectomy System (Possis Medical, Inc., Minneapolis,
      Minnesota) is an effective thrombectomy device, but it may cause bradycardias
      ranging from mild bradycardia to asystole and hypotension in some patients. The
      incidence appears to be higher with the proximity of the device to the heart.
      Several hypotheses have attempted to explain and attenuate this phenomenon.

PMID- 18830015
TI  - Guidewire pacing safely and effectively treats bradyarrhythmias induced by
      rheolytic thrombectomy and precludes the need for transvenous pacing: the Scott &
      White experience.
AB  - Rheolytic thrombectomy (RT) is useful in certain percutaneous coronary
      interventions but may be associated with transient bradyarrhythmias. Clinicians
      have devised numerous strategies to deal with these arrhythmias apart from
      transvenous right ventricular pacing, some of which are described in other parts
      of this supplement. We report the Scott & White experience utilizing guidewire
      pacing to quickly and safely pace the heart in the event of bradyarrhythmia. We
      found this method to be safe and reliable (96.2% successful) during RT and now
      use this technique almost exclusively in the cardiac catheterization lab to deal
      with transient bradyarrhythmias during RT or due to any other cause.We also
      report an increased incidence of bradyarrhythmia occurring during RT when it is
      performed in the right coronary artery, with a trend toward an increased
      incidence during the clinical presentation of ST-elevation myocardial infarction.

PMID- 18830016
TI  - Aminophylline for prevention of bradyarrhythmias induced by rheolytic
      thrombectomy.
AB  - In patients with acute ST-elevation myocardial infarction or in those with
      thrombus-containing lesions, percutaneous coronary intervention (PCI) represents
      a clinical challenge to the interventionist, because coronary thrombus is a
      predictor of adverse outcomes. Thrombectomy, or the removal of thrombusfrom the
      infarct-related vessel prior to PCI, might improve clinical outcomes. The
      AngioJet Rheolytic Thrombectomy System (Possis Medical, Inc., Minneapolis,
      Minnesota) is commonly used to treat lesions containing thrombus burden. A
      complication of rheolytic thrombectomy is transient cardiac rhythm disturbances,
      specifically bradyarrhythmia requiring temporary pacing. Aminophylline, a
      methylxanthine and a competitive inhibitor of the adenosine receptor, may prevent
      rheolytic thrombectomy-associated bradyarrhythmias. This report describes the use
      of aminophylline alone to prevent rheolytic thrombectomy-induced bradyarrhythmias
      in a single tertiary care center.

PMID- 18830017
TI  - Intracoronary aminophylline for management of bradyarrhythmias during
      thrombectomy with the AngioJet catheter.
AB  - Thrombectomy with the AngioJet rheolytic thrombectomy catheter frequently causes
      bradyarrhythmias. This necessitates temporary pacemaker insertion and limits the
      device's use. Novel approaches for treatment of bradyarrhythmias are being
      tested. This article focuses on the evidence supporting the role of adenosine in
      bradyarrhythmias during thrombectomy and presents; data from a porcine model and
      the first human experience supporting the use of aminophylline, a competitive
      inhibitor of the adenosine receptor, via an intracoronary route, for prevention
      of bradyarrhythmias during thrombectomy.

PMID- 18830018
TI  - Can glycopyrrolate replace temporary pacemaker and atropine in patients at high
      risk for symptomatic bradycardia undergoing AngioJet mechanical thrombectomy?
AB  - We studied the feasibility and efficacy of glycopyrrolate, a synthetic
      anticholinergic agent with shorter half-life and without reflex tachycardia, in
      preventing symptomatic bradycardia in patients undergoing mechanical thrombectomy
      with the AngioJet Rheolytic Thrombectomy System (Possis Medical, Inc.,
      Minneapolis, Minnesota). There was no need for temporary pacemaker insertion and
      no hemodynamically significant bradycardia in 10 consecutive patients.
      Additionally, there were no adverse effects from glycopyrrolate therapy. Our
      pilot study demonstrates that glycopyrrolate may replace temporary pacemaker
      insertion in these patients at high risk for symptomatic bradycardia.

PMID- 18830019
TI  - Management of dysrhythmias during coronary AngioJet: how to minimize the need for
      temporary pacemaker during rheolytic thrombectomy.
AB  - BACKGROUND: Whatever the mechanism or mechanisms involved in the genesis of
      bradyarrhythmias during rheolytic thrombectomy (RT), the severity and duration of
      bradycardia are related to vessel location and the duration of the activation of
      the RT catheter. The latter implies that procedural variables may have a role in
      the prevention or attenuation of bradycardia and subsequent minimization of the
      need for temporary pacemaker insertion. METHODS: From January 2004 to December
      2007, 396 patients with ST-segment elevation acute myocardial infarction received
      RT using the single-pass anterograde technique. All but 2 patients had RT without
      temporary pacemaker support. The 2 patients with temporary pacemakers received
      the electrical support before arriving in the cath lab. RESULTS: No major
      clinical adverse events related to bradyarrhythmias occurred. CONCLUSION: The
      single-pass anterograde RT technique minimizes the need for temporary pacemaker
      insertion and is safe and effective.

PMID- 18830020
TI  - Conclusion: Novel approaches to managing bradycardia during coronary rheolytic
      thrombectomy.

PMID- 18830021
TI  - [Variability of C-structural heterochromatin in cells derived from the patients
      with cardiomiopathy and from their relatives].
AB  - Variability of C-structural heterochromatin segments in chromosome 1,9 and 16 has
      been studied in lymphocyte cultures of peripheral blood taken from the patients
      with the hypertrophy (HC) and dilatate (DC) forms of cardiomiopathy and their 1st
      degree relatives (32 individuals, in total). 10 healthy individuals composed the
      control group. C-segments were sorted according to Patil and Lubs: a<0.5 x 16p;
      b>0.5-1 x 16p; c>1.5 x 16p; d>1.5-2 x 16p; e>2 x 16p. The total amount of C
      heterochromatin in all the studied chromosomes was tended to increase for DC
      patients and the relatives of the patients with the two forms of cardiomiopathy.
      Individual specificity within the group was found when the c-variants were
      assessed in chromosomes. In particular, the results obtained in cells of HC
      patients and their relatives did not differ from the control values, while the
      distribution pattern of C-segments within the group of DC patients and their
      relatives underwent changing. The elevated induces of pericentromeric inversion
      were found in all the patients with both forms of the disease and their relatives
      indicating C-structural heterochromatin polymorphism in the tested individuals.

PMID- 18830022
TI  - [The effect of heavy metal ions and peptide bioregulators on the expression of
      chromosome fragile sites in the individuals of different age groups and breast
      cancer patients].
AB  - Expression rates of chromosome fragile sites in peripheral blood lymphocytes have
      been studied in clinically healthy individuals of different age groups (20-38 yrs
      and 75-86 yrs) and breast cancer patients (8 cases). In individuals with a normal
      check-up of different age groups the heavy metal (nickel, zinc and cobalt) ions
      were also examined on their influence on the expression of the fragile sites and
      the peptide bioregulators (Livagen and Epithalon) were tested on their ability to
      correct the pattern of expression. Short-term lymphocyte cultures were used as
      tested material. The analysis showed that the chromosomes of people from young
      and old age groups differ from each other by the expression pattern of fragile
      sites - the chromosomes of young individuals were found to be more active by
      spontaneous formation of fragile sites. They were also sensitive to their
      induction by heavy metals. Both tested bioregulators lessen heavy metals effect
      that was statistically reliable only for the young people group. As for the
      patients with breast cancer general elevated fragility of chromosomes and
      specific distribution of the fragile sites along the chromosomes were revealed.

PMID- 18830023
TI  - The microcalorimetric investigation of cellular suspensions of blood lymphocytes
      from healthily and suffering from atherosclerosis individuals.
AB  - The denaturation thermodynamic parameters--enthalpy (DeltaH) and temperature of
      hetero-and active chromatin of lymphocytes and metabolic heat of these cells were
      determined for healthy and suffering from atherosclerosis individuals. It is
      supposed that atherosclerosis disease leads to chromatin rebuilding in the
      interphase state and decrease of cell survival. The chromatin rebuilding may be
      imagined as partially unfolding of 30 nm chromatin fiber into 10 nm one due to
      loss of some part of H1 histone.

PMID- 18830024
TI  - Thermodynamic properties of blood plasma of patient suffering from
      atherosclerosis.
AB  - The goal of the work is to find out the changes in the heat parameters of blood
      plasma denaturation of a son and a granddaughter, in comparison with the same
      parameters of a 91 years old grandfather with atherosclerosis. The significant
      changes in heat (Q(d)) and denaturation temperature (T(d)) of albumin, globulins
      and fibrinogen of 91-year-old patient suffering from atherosclerosis relative to
      the norm (88-year-old man) are found out. In particular, Q(d) increase by 60% of
      albumin fat fraction and fibrinogen of F domain and the increase of their T(d) by
      2.4 degrees C and 2.8 degrees C relative to the norm; Q(d) decrease by 1.8 times
      and T(d) increase by 2.9 degrees C of gamma globulin relative to the norm; Q(d)
      decrease by 6 time of D domain fibrinogen and and globulins by 1.4 and 2.9 times
      relative to the norm. Total denaturation heat of donor blood plasma is equal to
      25.5+/-3 J/g and patient suffering from atherosclerosis is equal to 22.0 J/g. The
      most significant changes of heat parameters are observed between grandfather and
      granddaughter: an increase of D domain T(d) by 4 degrees C and Q(d) by 6 times;
      T(d) increase of albumin fat fraction by 4.3 degrees C and its Q(d) decrease by
      10% of granddaughter in comparison with her grandfather. As value Qd of proteins
      is directly proportional to protein concentration in solutions, we conclude that
      the significant changes of concentration main proteins in blood plasma and
      changes of their thermodynamic stability occur at atherosclerosis, relative to
      the norm.

PMID- 18830025
TI  - Proinflammatory reactants as determinants of stroke severity in elderly.
AB  - Investigations aimed at studying of peripheral blood levels of free nitric oxide
      (NO) and proinflammatory cytokines IL-1beta, IL- 6 and TNF-alpha in correlation
      with initial ischemic lesion size and neurological dynamics during a month of
      acute brain ischemia. Forty two patients aged 60-75 (26 male) have been
      investigated. Initial neurological status, later deterioration and functional
      outcome were evaluated using Glasgow Coma Scale (GCS), National institutes of
      Health Stroke Scale (NIHSS) and Barthel Index (BI). Patients were divided into
      two groups: severe stroke (GCS<or=10, NIHSS >15, BI<16, n=25) and a moderate/mild
      stroke (GCS>10, NIHSS<or=15, BI>or=18, n=17). The NO concentration was detected
      by spectrophotometric and Electron Paramagnetic Resonance (EPR) methods. Cytokine
      plasma levels were determined applying the Enzyme-Linked Immuno Sorbent Assay
      (ELISA). Statistical evaluation was performed by SPSS. Mean values calculated
      using the t-paired test. Pearson correlation ad multivariate logistic regression
      have been applied. In the first days of stroke onset the plasma levels of IL
      1beta and TNF-alpha revealed the slight negative correlation toward the
      functional outcome, while the elderly patients found to have the significant
      negative correlation of IL-6 plasma levels toward the functional outcome
      (p<0.01). The NO plasma concentration within 48 hours after stroke onset more
      profoundly was reduced in aged patients, while in less severe cases and in
      relatively young patients it was significantly elevated (p<0.01). The high plasma
      level of IL-6 in the acute phase of stroke seems to be the strong predictor of
      poor outcome rather for aged, than for younger patients.

PMID- 18830026
TI  - Genetic changes induced by the pesticide Ridomol in the soybeans sprouted from
      the seeds of different ages.
AB  - An objective of presented study was to investigate the effect of the genetically
      active xenobiotics Ridomili on the genetic apparatus of the plants sprouted from
      the soybean seeds of different ages. The experiments were conducted on the
      soybean (Glycine max) genetic line L65-1237. The studies were performed on the 1
      , 2- or 3- year old seeds of the heterozygous Y(11)y(11) plants. The seeds of
      different ages were exposed to the pesticide Ridomili diluted in distilled water
      in different concentrations--0.02%, 0.04%, 0.06%, 0.08% and 0.1%. Three phenotype
      classes--green (Y(11)Y(11)), light-green (Y(11)y(11)) and yellow (y(11)y(11)) in
      proportion 1:2:1. All the concentrations of the substance caused mitotic
      crossingovers in the plants sprouted from the 3-year-old seeds. The higher doses
      of Ridomil (0.06-0.1%) caused induction of reversions much more frequently than
      in the case of 1- and 2-year-old seeds. The tendency to the dose-dependant effect
      was also observed. Embryonic cells of 3-year-old seeds were found to be highly
      sensitive. The levels of direct mutations were rather common there.

PMID- 18830027
TI  - Ras proteins, nitrosylation and homocysteine metabolism.
AB  - Elevated levels of homocysteine and S-adenosylmethionine are causal risk factors
      for several neurological disorders. Homocysteine is a sulfur-containing,
      nonproteinogenic, neurotoxic amino acid biosynthesized during methyl cycles after
      demethylation of S-adenosylmethionine (SAM) to adenosylhomocysteine (SAH) and
      subsequent hydrolysis of SAH into homocysteine and adenosine. PC12
      pheochromocytoma cells expressing a dominant inhibitory mutant of Ha-ras (M-M17
      26, PC12 pheochromocytoma cells expressing a mutant v-ras gene (MVR) and PC12
      cells transfected with normal c-rasH (M-CR3B) has been used to investigate the
      role of nitrosylation and farnesylation of Ras on the production of homocysteine
      and the activities of the redox-sensitive transcription factors NF-kB and c-Fos.
      We found that under serum and nerve growth factor withdrawal conditions
      undifferentiated apoptotic M-CR3B cells accumulated more homocysteine, than M-M17
      26 cells and the production of homocysteine decreased under the action of
      manumycin (inhibitor of farnesyltransferase) and increased in the presence of L
      NAME (inhibitor of nitric oxide synthase). Furthermore, we have shown that
      manumycin increased the activity of c-Fos in the M-CR3B cells and decreased the
      activity of NF-kB, while L-NAME reduced the activities of both transcription
      factors, and accelerated apoptosis of M-CR3B cells. In contrast to the M-CR3B
      cells, in M-M17-26 cells manumycin did not change the activity of c-Fos or the
      activity of NF-kB. Moreover, we have shown that L-NAME significantly changes the
      SAM/SAH ratio in both MCR and MVR cells. Moreover, these alterations have
      reciprocal character; in the MCR cells, the SAM/SAH ratio was raised, whereas in
      the MVR cells this ratio was reduced. We conclude that trophic factor withdrawal
      stimulates Ras, which apparently through the Rac/NADPH oxidase system induces
      permanent oxidative stress, modulates the activities of NF-kB and c-Fos, induces
      production of homocysteine and accelerates apoptosis. Nitrosylation of Ras is
      necessary for maintaining the survival of PC12 cells, while farnesylation of Ras
      stimulates apoptosis under withdrawal conditions. Besides, our results suggest
      that in conditions of a low level of nitric oxide PC12 cells with mutated
      oncogenic Ras produce more ROS than cells with wild type Ras and switch
      homocysteine metabolism toward to transsulfuration.

PMID- 18830028
TI  - [The age-dependent effect of copper ions on different strains of the wine yeast
      (Saccharomyces [corrected] cerevisiae var vini)].
AB  - The chronological ageing of wine yeast strains isolated from natural populations
      and the resistance of cells of different age to copper ions have been studied. In
      total, 25 wine yeast strains derived from the "Tsolikauri" population of Sviri
      village (Imereti, West Georgia) were tested. The strains were transferred to the
      standard (control samples) and the copper sulphate-containing complete media and
      stored at 2 degrees C temperature. 10, 20 and 30 days after setting up the
      cultures their resistance to copper ions were examined. Methylene blue dye was
      used for identification of survived cells. Young strain cultures have revealed
      different resistance to copper ions. The strains under investigation may be
      conditionally divided into three morphs, such as: "sensitive" (capable of growing
      on 1-2 mM medium. 6 strains belong to this group), "mild" (grow on 3-4 mM medium-
      17 strains and "resistant" (can grow on 5 mM medium, includes 3 strains). The
      population was found to be polymorphic by the resistance to copper ions. The
      "sensitive" and "resistant" strains in spite of ageing (10 or 20 days after the
      onset of culturing) retain their resistance to copper ions, while the "mild"
      morphs exhibited some degree of variability. In the "aged" (30-day long) cultures
      strong inhibitory activity of copper ions was apparently observed. In contrast to
      the others, the resistance was sustained in the "resistant" morphs. The frequency
      of living cells was defined in the strains grown on the control and copper ion
      containing substrates. Survived and died cells were counted. The strains belonged
      to the sensitive morphs contained high number of died cells--26-30%. The same
      index was rather low in the other morphs with no difference between them. Further
      ageing of the cultures (30 days and more) caused so sharp decrease in the
      liability of the strains, that they completely lose their resistance. Thus, the
      examined populations of the wine yeast were found to be polymorphic by their
      lifespan. They differ from each other by the speed of chronological ageing, that
      should be attributed to their genetic structure.

PMID- 18830029
TI  - [The effect of chemotherapy treatment on hemostasis of patients with lung
      cancer].
AB  - Chemotherapy is known to raise the risk of developing thrombotic complications.
      The aim of our work is to study the system of hemostasis in patients with the
      lung cancer under chemotherapy treatment. 61 patients were examined (40 men, 21
      women) between the ages of 32 and 75 years (the principal group). Chemotherapy
      was prescribed to 52 patients with the lung cancer considered as non-operable
      ones, and to 9 patients who refused surgical treatment. Chemotherapy applied to
      the patients was done by the conventional scheme. The treatment has been
      conducted from 16 to 20 days.Thrombocytic-vascular hemostasis, plasmatic
      hemostasis, physiological anticoagulant activity, the blood fibrinolytic
      activity, markers of intravascular coagulation of the blood and those of
      fibrinolysis, were studied. The depletion of compensatory mechanisms at all
      segments of hemostasis in non-operable patients was revealed. The type of
      reaction points at an oppressive effect of chemodrugs on the hemostasis system
      and the increase of the risk of development thrombotic complications in those
      patients.

PMID- 18830030
TI  - [Modern approaches to treatment of thrombosis in pregnant women, carriers of
      hereditary anomalies--F-V-Leiden and G20210A mutation].
AB  - AIM OF INVESTIGATION: studying of efficiency low-molecular heparin for preventive
      maintenance and treatment of thromboembolic disorders in pregnant women, carriers
      of F-V- L and F-II-20210 G-A mutation. Under supervision, there were 27 women
      with thrombosis during pregnancy from 19 to 39 years old. The lower extremities
      veins thromboses was diagnosed by duplex sonography. F-V- Leiden, F-II-20210 G-A
      and MTHFR C 677T gene mutation was defined by PCR-PELP method. To all pregnant
      women Fraxiparin and vitamins of B group was appointed during pregnancy period;
      at presence of MTHFR a folic acid was appointed in addition. It is concluded that
      application of Fraxiparin is an effective method of treatment of thrombosis
      during pregnancy and women--carriers F-V- Leiden, F-II-20210 G-A and MTHFR C 677T
      gene mutation. High efficiency of Fraxiparin confirms with change of parameters
      of various parts of a hemostasis and return development of thrombosis evidence.

PMID- 18830031
TI  - Treatment of patients with cardiogenic shock in the setting of acute myocardial
      infarction. Case reports.
AB  - Cardiogenic shock remains unsolved problem in modern Cardiology. Despite some
      achievements, in-hospital mortality rate still varies between 52-70%. In era of
      new developments in the field of circulatory assist devices IABP still remains
      the main supportive method for patients with shock. The most powerful predictors
      of hospital survival among shock patients are percutaneous revascularization with
      stenting and use of Intra-Aortic Balloon Counterpulsation (IABP). As we have
      experienced: inability to establish circulatory assistance can be fatal even with
      "open coronaries". Here we want to represent three cases of treatment of patients
      with ST Elevation Acute Myocardial Infarction complicated with cardiogenic shock.

PMID- 18830032
TI  - [Positive effects of angiotensin [corrected] receptor blockers on the course of
      microvascular complications of diabetes mellitus].
AB  - The aim of the research was to evaluate some clinical and hemodynamic
      characteristics in patients with diabetes mellitus type 1 and type 2 (DM type 1
      and DM type 2), to diagnose diabetic retinopathy (DR) on early stage of its
      development for the correction of the disease by treating with angiotensin II
      type 1 receptor blocker (AT I)--Candesartan. Totally 250 patients (pts) with DM
      type 1 and DM type 2 were studied; they were divided into 3 groups (Gr.): Gr.1
      (n=115)--pts with DM and without DR; Gr. 2 (n=43)--pts with DM type 1 and DR;
      Gr.3 (n=92)--pts with DM type 2 and DR. A comprehensive physical examination was
      conducted to obtain baseline information about the patient: clinical status,
      lipid profile, microalbuminuria and urine creatinine, as well as glycemia levels.
      Patients were treated with Candesartan (16 or 32 mg) or placebo. When necessary,
      other antihypertensive agents (except ACE-inhibitors) were initiated. Eye fundus
      monitoring was performed with evaluation of 7,300 standard zone stereoscopic
      pictures of the retina according to ETDRS (Early Treatment of Diabetic
      Retinopathy Study). The results of three year observation revealed no pathologic
      changes on the retina in normotensive and normoglycemic pts; pts with mild
      diabetic retinopathy at baseline demonstrated normal levels of ABP and blood
      glucose which resulted in the regression of the changes. The changes of various
      severity demonstrated no positive shifts in 96% of cases; DR deterioration
      (proliferative DR, neovascularisation stage) was observed in 4% of cases. Results
      of the study showed that Candesartan treatment of pts with DM resulted in
      positive shifts in the pathologic changes, registered on the retina and decrease
      in urine albumin excretion rate. Thus, we recommend to include Candesartan in the
      standard treatment, as the have positive effect on the course microvascular
      complications of diabetes mellitus both in males and females.

PMID- 18830033
TI  - Restoring movement to paralyzed limbs by treating nerve root avulsion: a seven
      year retrospective.
AB  - Traumatic injury of major nerve roots of extremities paralyzes the limb and
      causes high degree of disability. The aim of the study was to evaluate outcomes
      of surgical treatment of upper and lower limb nerve root avulsion using various
      microsurgical techniques to reconstruct the function of the extremity. 31
      contralateral nerve transfer surgeries were performed on 17 patients with upper
      and lower extremities nerve root avulsion. Neurological and EMG examinations were
      carried out. To assess the return of function in the patient's hand Medical
      Research Council grading systems were used; to evaluate the return of function in
      the patient's leg we developed special microsurgical techniques. Excellent and
      good outcomes were received after thoracodorsal to musculocutaneous, spinal
      accessory to suprascapular or axillar in comparison to unlar to median or femoral
      transfer. Spinal accessory to suprascapular nerve transfer revealed better
      shoulder abduction than in case of spinal accessory to axillary transfer. It is
      concluded that contralateral nerve transfer represents a reliable and potent
      neurotizer that allows restoration of paralyzed limb function in surgical
      treatment of nerve root avulsion. Early reveal the better outcome.

PMID- 18830034
TI  - [Goals of treatment for osteoporosis].
AB  - Clinical practice is based on the data obtained in the randomized clinical trials
      with robust statistical power. Results of meta-analysis including plural
      randomized trials are also reliable, directly indicating the consistency of the
      efficacy of the treatment. Osteoporosis, a reduction in bone strength, is a
      disease of increased fracture risk, leading to enforced morbidity due to chronic
      pain and skeletal deformity and consequent increase in mortality. Thus, the
      reduction in fracture risk is just a prerequisite, and the decreases in morbidity
      and mortality are expected as the further goal of osteoporosis treatment.
      Evidences have been accumulated to indicate that treatments with amino
      bisphosphonates reduce fracture risk, maintain ADL and QOL, and decrease the
      death rates. Osteoporosis treatment is greatly recommended to improve the general
      health condition in elderly people.

PMID- 18830035
TI  - [Evidence of dietary therapy for osteoporosis].
AB  - A significant point of dietary therapy for osteoporosis is that calcium, vitamin
      D and vitamin K are recommended to be actively administered on top of sufficient
      intake of energy and the other nutrients including protein. In Japanese
      guidelines for the prevention and treatment of osteoporosis 2006 edition, daily
      intake of calcium and vitamin D is encouraged at least 800mg and 400 to 800IU (10
      to 20microg) , respectively. Calcium and vitamin D are also important for
      maximizing the effect of drug for osteoporosis. Calcium and vitamin D
      supplementation could be a supportive measure, when their necessary requirement
      is difficult to be consumed.

PMID- 18830036
TI  - [Exercise for people with osteoporosis].
AB  - In comprehensive treatment for osteoporosis, exercise, as well as
      pharmacotherapy, plays an important part to prevent falls and fractures and
      reduce lumbar pain improving muscular strength and physical balance. The aerobic
      exercise, especially walking, is also recommended for patients with osteoporosis.
      Although many studies have been performed to evaluate the effect of exercise in
      terms of reduction of falls and increase of bone density, no clinical study with
      a large number of patients which proved the effect of fracture prevention by
      exercise has been carried out. Combination of selected exercise in a long
      duration is essential to obtain effectiveness of exercise to prevent osteoporosis
      and osteoporosis-related fractures.

PMID- 18830037
TI  - [Alendronate].
AB  - Alendronate is one of a few pharmaceutical agents that have evidence to protect
      both vertebral and non-vertebral fracture. Here I review its effects on fracture
      prevention, as well as on surrogate markers such as bone mineral density, height
      loss, metabolic bone markers. Its effects on activities of daily living and
      quality of life will also be touched upon.

PMID- 18830038
TI  - [Efficacy and tolerability of risedronate for the treatment of osteoporosis].
AB  - Bisphosphonates are now the most widely used drugs for osteoporosis. Three
      bisphosphonates are available in Japan, i.e. etidronate, alendronate and
      risedronate. In these bisphosphonates, risedronate as the third-generation
      bisphosphonate was shown in many RCTs to decrease bone resorption biomarkers and
      to increase BMD. The relative risk of new vertebral fractures and non-vertebral
      fractures was reduced by about 50% or more. Risedronate is one of the most
      effective agents for prevention of osteoporotic fractures. Once-weekly treatment
      with 17.5 mg risedronate showed equivalent efficacy to once-daily treatment with
      2.5 mg risedronate, and was well tolerated with favorable safety profiles
      compared with once-daily dosage regimen.

PMID- 18830039
TI  - [Evidence and utility of etidronate for the treatment of osteoporosis].
AB  - Etidronate is the first bisphosphonate for the treatment of osteoporosis in
      Japan. Etidronate is useful for the treatment of postmenopausal osteoporosis,
      glucocorticoid induced osteoporosis, osteoporosis in men, and disused
      osteoporosis. Etidronate is less effective than other bisphosphonate, such as
      alendronate and risedronate, in reduction of fracture risk especially non
      vertebral fracture, although bone mineral density in femoral neck is
      significantly increased.

PMID- 18830040
TI  - [Evidence of hormone replacement therapy for osteoporosis].
AB  - Postmenopausal bone estrogen deficiency causes rapid bone loss. Therefore hormone
      replacement therapy (HRT) has been considered as a rational therapy for
      postmenopausal not only for osteopenia but also osteoporosis. The results of
      Women's Health Initiative (WHI) hormone trial had given the strong restriction on
      HRT. However recent closer analyses have shown that HRT initiated for early
      menopausal women brings many benefits without elevation of the risks, and that
      the appropriate selection of dose level or a way to apply can also reduce the
      risks of HRT. HRT has many physiological effects that were not seen in other
      drugs and so HRT can be considered as one of the most effective treatment for
      postmenopausal osteoporosis.

PMID- 18830041
TI  - [Evidence for the selective estrogen receptor modulator raloxifene: its evolving
      role in the treatment of osteoporosis].
AB  - Several lines of evidence demonstrate that the objective of osteoporosis
      treatment consists in the prophylaxis of osteoporotic fractures. With the
      endpoint of osteoporosis treatment thus clarified, currently, the selective
      estrogen receptor modulator (SERM) raloxifine represents the mainstay of therapy
      for osteoporosis, together with the antiresorptive agents bisphosphonates. Thus,
      this review has drawn mainly on the results of the MORE study to explore the
      efficacy of raloxifene in inhibiting bone metabolism, increasing bone mineral
      density effects, and preventing bone fractures. Notably, the available evidence
      for raloxifene suggests that the efficacy of raloxifene in preventing bone
      fractures has not only to do with bone mineral density but also to do with bone
      quality.

PMID- 18830042
TI  - [Effect of anabolic steroids on osteoporosis].
AB  - Androgen inhibits osteoclastic bone resorption with increase of bone formation
      through androgen receptor in bone tissue. Anabolic steroids are synthetic
      derivates of testoterone. Anobolic steroids have favorable anabolic actions,
      lessening virilizing effects. Several anabolic steroids have been synthesized and
      some of them have been approved as a drug for anti osteoporosis. Anabolic
      steroids have revealed the increased bone mineral content or bone mineral density
      at the radius, and the lumbar spine in osteoporosis patients. Anabolic steroids
      have also decreased fat mass with increase of lean body mass and muscle mass, and
      lessened bone pain in osteoporosis patients having bone fracture, which seem to
      be favorable effects for especially elder osteoporosis patients. But in recent
      years the number of osteoporosis patients treated with anabolic steroids has been
      decreasing. Furthermore recently few clinical trials about the effect of anabolic
      steroids on osteoporosis have been reported, and prospective study for bone
      fracture using anabolic steroids has not reported yet. We would like to expect
      additional effects except on bone formation will enhance the frequency in use of
      anabolic steroids, and the prospective clinical study about the prevention
      against bone fracture will be reported in the future.

PMID- 18830043
TI  - [Calcitonin].
AB  - Calcitonin is a polypeptide hormone that bone resorption-inhibitory and analgesic
      effects, and has been used over many decades as a drug for the treatment of
      osteoporosis in Japan and overseas. Reports of large-scale studies of this
      hormone therefore as yet are few, compared to recently introduced drugs.
      Calcitonin is prescribed in injectable form in Japan while nasal spray
      preparations are widely used in Europe and the Unites States. Its characteristic
      effect of analgesia is slow in onset as compared with anti-inflammatory analgesic
      agents. A mechanism of action involving its serotonin receptor expression
      mediated effect on pain impulse transmission has been demonstrated. On account of
      this effect, calcitonin is recommended for use in the management of pain in
      patients with fresh vertebral fractures.

PMID- 18830044
TI  - [Evidence for efficacy of active vitamin D3 as an anti-osteoporotic drug].
AB  - Active vitamin D3 has been most widely used in Japan for the treatment of
      osteoporosis. Although it mildly increases bone mineral density, it has little
      consistent effect on bone metabolic markers, and clinical evidence for its
      efficacy as a fracture-preventing drug is rather weak. Recent reports suggest
      that (active) vitamin D3 may prevent fracture incidence not only by promoting
      intestinal calcium absorption but also by improving neuromuscular function to
      reduce the number of falls.

PMID- 18830045
TI  - [Vitamin K2].
AB  - Vitamin K2 has been approved for the treatment of osteoporosis in Japan since
      1995. Vitamin K2 treatment in osteoporosis has been shown to inhibit the
      occurrence of new bone fractures and to maintain BMD. The uniqueness of the
      prevention of bone fractures by vitamin K2 is that there has been no direct
      evidence of the relationship between increase of BMD and a decrease in the
      occurrence of bone fractures. A recent systematic review of seven Japanese
      randomized controlled trials by Cockayne has also shown that supplementation with
      phytonadione (Vitamin K1) and menaquinone (Vitamin K2) , particularly menaquinone
      4, is associated with increased BMD and reduced fracture incidence. To confirm
      these results, a larger well design RCT using fractures as the primary endpoint
      is clearly needed.

PMID- 18830047
TI  - [Bone disease with pain. Tibial plateau fracture].
AB  - Fractures that involve the proximal tibia affect knee kinematics and stability.
      Especially tibial prateau fractures are intra-articular injuries, impair not only
      metaphyseal bone but articular cartilage, meniscus and ligament. Basically the
      ideal treatment for tibial plateau fractures should be an anatomic reduction with
      stable fixation allowing weight bearing training and an early range of motion
      exercise, it is the reason that the indication of conservative treatment is
      limited. Open rudection and bone grafting followed by a buttress plate fixation
      is a general treatment for tibial plateau fracture. I have tried to use the
      arthroscopic technique for selected cases. Utilizing arthroscopic assist,
      accurate diagnosis and treatment of any associated joint pathology was possible,
      and an anatomical reduction was obtained. The aim of surgical treatment of tibial
      plateau fracture is to restore a congruity of joint by anatomical reduction of
      articular surface, and to achieve enough stability permitting early pain free
      range of motion training. Finally, the goal of treatment is to preserve normal
      knee function and to prevent developing post-traumatic arthrosis in the future.

PMID- 18830046
TI  - [Newly developed drugs for osteoporosis in overseas and their future roles for
      the therapy].
AB  - Bisphosphonates are widely used, though gastrointestinal tolerance is a problem
      on daily administration. Intermittent regimen, from once weekly to once yearly,
      is now available in overseas and can overcome GI adverse events. New generation
      of anti-resorptive agents (anti-RANKL antibody and a new SERM, bazedoxifene) are
      promising and will be soon available for the treatment of osteoporosis. Anabolic
      agents such as teriparatide and strontium ranelate have marked effects on BMD and
      reduction on fracture risk. While none of these options is suitable for everyone,
      the range of future available therapies does mean that most patients can find an
      intervention that is effective and acceptable.

PMID- 18830048
TI  - [Nutrition and bone health during childhood].
AB  - Nutritional aspects of the bone mineral accruals during childhood were discussed.
      Calcium is the most important mineral for bone and large number of studies has
      been performed to clarify the effects of the calcium supplement on bone strength
      or bone mineral gain during childhood. One recent meta-analysis showed that
      calcium supplement has only minor effect on bone mineral accruals. But the
      effects seemed to be larger in the group whose basal calcium intake was small. In
      Japan, basal calcium intake is low. Thus we should be careful to evaluate the
      effects of calcium supplement on bone. Vitamin D is another important nutrition.
      Food restriction, especially fish and egg yolk, is the major cause of vitamin D
      deficiency in Japan.

PMID- 18830049
TI  - Clinical and pathological aspects of filarial lymphedema and its management.
AB  - Lymphatic filariasis, transmitted by mosquitoes is the commonest cause of
      lymphedema in endemic countries. Among 120 million infected people in 83
      countries, up to 16 million have lymphedema. Microfilariae ingested by mosquitoes
      grow into infective larvae. These larvae entering humans after infected mosquito
      bites grow in the lymphatics to adult worms that cause damage to lymphatics
      resulting in dilatation of lymph vessels. This earliest pathology is demonstrated
      in adults as well as in children, by ultrasonography, lymphoscintigraphy and
      histopathology studies. Once established, this damage was thought to be
      irreversible. This lymphatic damage predisposes to bacterial infection that
      causes recurrent acute attacks of dermato-lymphangio-adenitis in the affected
      limbs. Bacteria, mainly streptococci gain entry into the lymphatics through
      'entry lesions' in skin, like interdigital fungal infections, injuries, eczema or
      similar causes that disrupt integrity of skin. Attacks of dermato-lymphangio
      adenitis aggravates lymphatic damage causing lymphedema, which gets worse with
      repeated acute attacks. Elephantiasis is a late manifestation of lymphatic
      filariasis, which apart from limbs may involve genitalia or breasts. Lymphedema
      management includes use of antifilarial drugs in early stages, treatment and
      prevention of acute attacks through 'limb-hygiene', antibiotics and antifungals
      where indicated, and physical measures to reduce the swelling. In selected cases
      surgery is helpful.

PMID- 18830050
TI  - Effects of excretory/secretory products from Clonorchis sinensis and the
      carcinogen dimethylnitrosamine on the proliferation and cell cycle modulation of
      human epithelial HEK293T cells.
AB  - Clonorchis sinensis is one of the most prevalent parasitic helminths in Korea.
      Although cholangiocarcinoma can be induced by C. sinensis infection, the
      underlying mechanism is not clearly understood. To assess the role of C. sinensis
      infection in carcinogenesis, an in vitro system was established using the human
      epithelial cell line HEK293T. In cells exposed to the excretory/secretory
      products (ESP) of C. sinensis and the carcinogen dimethylnitrosamine (DMN),
      cellular proliferation and the proportion of cells in the G2/M phase increased.
      Moreover, the expression of the cell cycle proteins E2F1, p-pRb, and cyclin B was
      dramatically increased when ESP and DMN were added together. Similarly, the
      transcription factor E2F1 showed its highest level of activity when ESP and DMN
      were added simultaneously. These findings indicate that DMN and ESP
      synergistically affect the regulation of cell cycle-related proteins. Our results
      suggest that exposure to C. sinensis and a small amount of a carcinogen such as
      DMN can promote carcinogenesis in the bile duct epithelium via uncontrolled
      cellular proliferation and the upregulation of cell cycle-related proteins.

PMID- 18830051
TI  - Prevalence of clonorchiasis in southern endemic areas of Korea in 2006.
AB  - This study was performed to investigate prevalence of clonorchiasis among the
      inhabitants living in villages along the 4 major rivers, Nakdong-gang (=river),
      Seomjin-gang, Youngsan-gang, and Guem-gang in southern Korea. From January to
      December 2006, a total of 24,075 stool samples (1 sample per an inhabitant) were
      collected in 23 localities and examined by the formalin-ether sedimentation
      technique. Of the inhabitants examined, 3,441 (14.3%) were found to harbor
      various types of intestinal parasite eggs, cysts or larvae. Numbers of infected
      people were 2,661 (11.1%) for Clonorchis sinensis, 431 (1.8%) for heterophyids,
      226 (0.9%) for Entamoeba spp., 57 (0.2%) for Giardia lamblia, 30 (0.1%) for
      Trichuris trichiura, and 18 (0.07%) for echinostomes. Prevalence rates of
      clonorchiasis according to the river basin were 17.1% in Nakdong-gang, 11.2% in
      Seomjin-gang, 5.5% in Youngsan-gang and 4.6% in Guem-gang. Of the 2,661 C.
      sinensis egg-positive cases, 57.7% was male. The present findings suggest that
      clonorchiasis is still highly prevalent among inhabitants in the riverside areas
      of southern Korea, and it is necessary to implement a systematic control program
      in the endemic areas.

PMID- 18830052
TI  - Toxocariasis and ingestion of raw cow liver in patients with eosinophilia.
AB  - Ingestion of raw animal liver has been suggested as a possible mode of infection
      of human toxocariasis. We evaluated the relationship between toxocariasis and the
      ingestion of raw meat in patients with eosinophilia of unknown etiology. The
      study population consisted of 120 patients presenting with peripheral blood
      eosinophilia (>500 cells/microliter or >10% of the white blood cell count). They
      were divided into 2 groups: 104 seropositive patients based on a Toxocara
      excretory-secretory IgG ELISA and 16 seronegative patients. While 25.0% of
      seronegative patients had a recent history of eating raw cow liver, 87.5% of
      seropositive patients had this history. Multivariate statistical analysis showed
      that a recent history of eating raw cow liver was related to an increased risk of
      toxocariasis. Collectively, it is proposed that raw cow liver is a significant
      infection source of toxocariasis in the patients with eosinophilia of unknown
      etiology.

PMID- 18830053
TI  - Suppressed production of pro-inflammatory cytokines by LPS-activated macrophages
      after treatment with Toxoplasma gondii lysate.
AB  - During Toxoplasma gondii infection, macrophages, dendritic cells, and neutrophils
      are important sources of pro-inflammatory cytokines from the host. To counteract
      the pro-inflammatory activities, T. gondii is known to have several mechanisms
      inducing down-regulation of the host immunity. In the present study, we analyzed
      the production of proand anti-inflammatory cytokines from a human myelomonocytic
      cell line, THP-1 cells, in response to treatment with T. gondii lysate or
      lipopolysaccharide (LPS). Treatment of THP-1 cells with LPS induced production of
      IL-12, TNF-alpha, IL-8, and IL-10. Co-treatment of THP-1 cells with T. gondii
      lysate inhibited the LPS-induced IL-12, IL-8 and TNF-alpha expression, but
      increased the level of IL-10 synergistically. IL-12 and IL-10 production was down
      regulated by anti-human toll-like receptor (TLR)-2 and TLR4 antibodies. T. gondii
      lysate triggered nuclear factor (NF)-kappaB-dependent IL-8 expression in HEK293
      cells transfected with TLR2. It is suggested that immunosuppression induced by T.
      gondii lysate treatment might occur via TLR2-mediated NF-kappaB activation.

PMID- 18830054
TI  - Inhibitory effects of Iranian Thymus vulgaris extracts on in vitro growth of
      Entamoeba histolytica.
AB  - One of the most common drugs used against a wide variety of anaerobic protozoan
      parasites is metronidazole. However, this drug is mutagenic for bacteria and is a
      potent carcinogen for rodents. Thymus vulgaris is used for cough suppression and
      relief of dyspepsia. Also it has antibacterial and antifungal properties. The aim
      of this study was to investigate antiamebic effect of Thymus vulgaris against
      Entamoeba histolytica in comparison with metronidazole. One hundred gram air
      dried T. vulgaris plant was obtained and macerated at 25 degrees C for 14 days
      using n-hexane and a mixture of ethanol and water. For essential oil isolation T.
      vulgaris was subjected to hydrodistillation using a clevenger-type apparatus for
      3 hr. E. histolytica, HM-1: IMSS strain was used in all experiments. It was found
      that the minimal inhibitory concentration (MIC) for T. vulgaris hydroalcoholic,
      hexanic extracts, and the essential oil after 24 hr was 4 mg/mL, 4 mg/mL, and 0.7
      mg/mL, respectively. After 48 hr the MIC for T. vulgaris hydroalcoholic and
      hexanic extracts was 3 and 3 mg/mL, respectively. Therefore, it can be concluded
      that the Iranian T. vulgaris is effective against the trophozoites of E.
      histolytica.

PMID- 18830055
TI  - Keratitis by Acanthamoeba triangularis: report of cases and characterization of
      isolates.
AB  - Three Acanthamoeba isolates (KA/E9, KA/E17, and KA/E23) from patients with
      keratitis were identified as Acanthamoeba triangularis by analysis of their
      molecular characteristics, a species not previously recognized to be a corneal
      pathogen. Epidemiologic significance of A. triangularis as a keratopathogen in
      Korea has been discussed. Morphologic features of Acanthamoeba cysts were
      examined under a microscope with differential interference contrast (DIC) optics.
      Mitochondrial DNA (mtDNA) of the ocular isolates KA/E9, KA/E17, and KA/E23 were
      digested with restriction enzymes, and the restriction patterns were compared
      with those of reference strains. Complete nuclear 18S and mitochondrial (mt) 16S
      rDNA sequences were subjected to phylogenetic analysis and species
      identification. mtDNA RFLP of 3 isolates showed very similar patterns to those of
      SH621, the type strain of A. triangularis. 16S and 18S rDNA sequence analysis
      confirmed 3 isolates to be A. triangularis. 18S rDNA sequence differences of the
      isolates were 1.3% to 1.6% and those of 16S rDNA, 0.4% to 0.9% from A.
      triangularis SH621. To the best of our knowledge, this is the first report,
      confirmed by 18S and 16S rDNA sequence analysis, of keratitis caused by A.
      triangularis of which the type strain was isolated from human feces. Six isolates
      of A. triangularis had been reported from contaminated contact lens cases in
      southeastern Korea.

PMID- 18830056
TI  - Microphallus koreana n. sp. (Trematoda: Microphallidae) transmitted by a marine
      crab, Macrophthalmus dilatatus.
AB  - Microphallus species occur primarily as intestinal parasites of birds and
      mammals, and metacercariae of a new species belonging to this genus have been
      discovered from the crab, Macrophthalmus dilatatus, in the Republic of Korea. The
      metacercaria of this fluke was round with 2 thick walls, and the excysted one had
      mature genital organs. The adult flukes recovered from experimentally infected
      chicks had numerous intrauterine eggs, well-developed pars prostatica, widely
      bifurcating ceca, and prominent uterine bulge. After observing internal
      structures, it was concluded that this species is different from any other known
      Microphallus spp. Based on the morphology of metacercariae and adult flukes, we
      describe this specimen as a new species, Microphallus koreana n. sp.

PMID- 18830057
TI  - Ectopic migration of an adult heartworm in a dog with dirofilariasis (case
      report).
AB  - A 3-yr-old female mongrel dog was referred to the Veterinary Teaching Hospital of
      Chungnam National University in the Republic of Korea. An adult heartworm,
      Dirofilaria immitis, was found in the abdominal cavity of the dog during spaying.
      Dirofilariasis in this dog was also diagnosed by modified Knott's test, ELISA
      test, and PCR analysis. The present case is the first report on the migration of
      an adult dog heartworm to the abdominal cavity of a dog in the Republic of Korea.

PMID- 18830058
TI  - Successful treatment of lupoid cutaneous leishmaniasis with glucantime and
      topical trichloroacetic acid (a case report).
AB  - Lupoid leishmaniasis is a unique form of cutaneous leishmaniasis characterized by
      unusual clinical features and a chronic relapsing course, mostly caused by
      infection with Leishmania tropica. In this clinical form, 1-2 yr after healing of
      the acute lesion, new papules and nodules appear at the margin of the remaining
      scar. Herein, we describe a case of this clinical form that was resistant to 2
      courses of treatments: systemic glucantime and then a combination therapy with
      allopurinol and systemic glucantime. However, marked improvement was seen after a
      combination therapy with topical trichloroacetic acid solution (50%) and systemic
      glucantime, and there were no signs of recurrence after 1 yr of follow-up.

PMID- 18830059
TI  - Skin test for paragonimiasis among schoolchildren and villagers in Namback
      District, Luangprabang Province, Lao PDR.
AB  - As a part of a broader effort to determine the status of Paragonimus species
      infection in Lao PDR, an epidemiological survey was conducted on villagers and
      schoolchildren in Namback District between 2003 and 2005. Among 308 villagers and
      633 primary and secondary schoolchildren, 156 villagers and 92 children evidenced
      a positive reaction on a Paragonimus skin test. Only 4 schoolchildren out of 128
      skin test-positive cases had Paragonimus sp. eggs in their sputum, all of which
      was collected on 1 day. Several types of crabs, which were identified as the
      second intermediate host of the Paragonimus species, were collected from markets
      and streams in a paragonimiasis endemic area for the inspection of metacercariae.
      Among the examined crabs, only "rock crabs" (Indochinamon ou) harbored
      Paragonimus sp. metacercariae, and it is speculated that the life cycle of
      Paragonimus sp. was maintained via rock crabs in Namback District, Lao PDR.

PMID- 18830060
TI  - Partial purification and characterization of a cysteine protease inhibitor from
      the plerocercoid of Spirometra erinacei.
AB  - Helminthic cysteine proteases are well known to play critical roles in tissue
      invasion, nutrient uptake, and immune evasion of the parasites. In the same
      manner, the sparganum, the plerocercoid of Spirometra mansoni, is also known to
      secrete a large amount of cysteine proteases. However, cysteine protease
      inhibitors regulating the proteolytic activities of the cysteine protease are
      poorly illustrated. In this regard, we partially purified an endogenous cysteine
      protease inhibitor from spargana and characterized its biochemical properties.
      The cysteine protease inhibitor was purified by sequential chromatographies using
      Resource Q anion exchanger and Superdex 200 HR gel filtration from crude extracts
      of spargana. The molecular weight of the purified protein was estimated to be
      about 11 kD on SDS-PAGE. It was able to inhibit papain and 27 kDa cysteine
      protease of spargana with the ratio of 25.7% and 49.1%, respectively, while did
      not inhibit chymotrypsin. This finding suggests that the cysteine protease
      inhibitor of spargana may be involved in regulation of endogenous cysteine
      proteases of the parasite, rather than interact with cysteine proteases from
      their hosts.

PMID- 18830061
TI  - House dust mite allergens in domestic homes in Cheonan, Korea.
AB  - House dust mites produce inhalant allergens of importance to allergic patients.
      We measured the major group 1 allergens, Der p 1 and Der f 1, from the house dust
      mites Dermatophagoides pteronyssinus and Dermatophagoides farina, respectively in
      100 randomly selected domestic homes from Cheonan, Korea. Dust samples were
      collected by vacuuming from the living room floor and 1 mattress in each home.
      Der p 1 and Der f 1 were measured by double monoclonal ELISA. Der p 1 levels were
      very low, with geometric mean levels for floors and mattresses being 0.11
      microgram/g (range: 0.01-4.05) and 0.14 microgram/g (range: 0.01-30.0),
      respectively. Corresponding levels of Der f 1 were higher, 7.46 microgram/g
      (range: 0.01-262.9) and 10.2 microgram/g (range: 0.01-230.9) for floors and
      mattresses, respectively. D. farinae appears to be the dominant house dust mite
      in Cheonan.

PMID- 18830062
TI  - Distribution frequency of pathogenic bacteria isolated from cutaneus
      leishmaniasis lesions.
AB  - Cutaneous leishmaniasis (CL) is a parasitic disease characterized by single or
      multiple ulcerations. Secondary bacterial infections are one of the complications
      that can increase the tissue destruction and the resulting scar. To better
      determine the incidence of real secondary bacterial infections in CL, we designed
      the current study. This was a cross-sectional study performed in Skin Diseases
      and Leishmaniasis Research Centre, Isfahan, Iran. A total of 1,255 patients with
      confirmed CL enrolled in the study. Sterile swaps were achieved for ulcer
      exudates and scraping was used for non-ulcerated lesions. All samples were
      transferred to tryptic soy broth medium. After 24 hr of incubation at 37 degrees
      C they were transferred to eosin methylene blue agar (EMB) and blood agar.
      Laboratory tests were used to determine the species of bacteria. Among 1,255
      confirmed CL patients, 274 (21.8%) had positive cultures for secondary bacterial
      infections. The bacteria isolated from the lesions were Staphylococcus aureus in
      190 cases (69.3%), coagulase negative Staphylococcus in 63 cases (23.0%), E. coli
      in 10 cases (3.6%), Proteus sp. in 6 cases (2.2%), and Klebsiella sp. in 5 cases
      (1.9%). The results show that the overall incidence of secondary bacterial
      infections in the lesions of CL was 21.8%, considerably high. The incidence of
      secondary bacterial infections was significantly higher in ulcerated lesions
      compared with non-ulcerated lesions.

PMID- 18830063
TI  - High levels of antibodies to Plasmodium falciparum liver stage antigen-1 in
      naturally infected individuals in Myanmar.
AB  - Plasmodium falciparum liver stage antigen-1 (PfLSA-1) is one of the few antigens
      expressed exclusively in liver stage parasites. In this study, we evaluated the
      antibody responses against recombinant PfLSA-1 in naturally infected individuals
      in Myanmar. High levels of antibody responses (70.7%) were detected in 82 serum
      samples from 116 infected individuals, and IgG responses to PfLSA-1 principally
      composed of responses of IgG1 and IgG3 subclasses. These results show that PfLSA
      1 elicits effective antibody responses in individuals infected with P.
      falciparum, and thus it could be not only an attractive candidate protein for
      vaccine development, but also a useful antigen for serodiagnosis of the
      infection.

PMID- 18830064
TI  - Prevalence of Toxoplasma gondii in stray cats of Gyeonggi-do, Korea.
AB  - Toxoplasma gondii is an obligate intracellular zoonotic protozoan with a
      worldwide distribution. It infects humans as well as a broad spectrum of
      vertebrate hosts. Cats and wild felidae play crucial roles in the epidemiology of
      toxoplasmosis. This study was performed to survey the prevalence of T. gondii
      infection among stray cats in the Gyeonggi-do, Republic of Korea. A total of 174
      stray cat blood samples were collected from Gwacheon-si (n=20), Bucheon-si (82),
      and Yangju-si (72). Positive sera for T. gondii were identified in 14 samples
      (8.1%) exclusively via the latex agglutination test, 28 (16.1%) via ELISA, and 23
      (13.2%) via PCR analysis. The overall infection rate of female stray cats (29.2%)
      presented as higher than that of male cats (24.0%). This study suggests that T.
      gondii is widespread in the stray cat population of Gyeonggi-do, Korea. It is
      urgently needed to control urban stray cat population and to reduce the risk of
      zoonotic transmission of toxoplasmosis to other animal hosts and humans.

PMID- 18830066
TI  - Contemporary management of fibromuscular dysplasia.
AB  - PURPOSE OF REVIEW: Fibromuscular dysplasia is an underdiagnosed and misunderstood
      disease. The purpose of this review is to inform healthcare providers and the
      public about a condition that may be more common than previously thought. RECENT
      FINDINGS: There has been little new information published about fibromuscular
      dysplasia in the past 30 years. The International Registry that is now underway
      will remedy that situation and provide a large number of patients to study with
      this condition. SUMMARY: Fibromuscular dysplasia is a noninflammatory,
      nonatherosclerotic disease that has been reported in almost every arterial bed
      and primarily affects women aged 15-50 years. It most commonly presents in the
      renal and extracranial cerebrovascular arteries, either manifesting as
      hypertension, transient ischemic attack or stroke, respectively. Some patients
      may be asymptomatic and fibromuscular dysplasia could only be discovered by
      imaging for some other reason or by the detection of an asymptomatic bruit.
      Dissection or aneurysm may also occur in patients with fibromuscular dysplasia.
      The true prevalence is unknown, partially because of the fact that it is
      underdiagnosed in many patients. Treatment consists of antiplatelet therapy for
      asymptomatic individuals and percutaneous balloon angioplasty for patients with
      indications for intervention. Patients with macroaneurysms should be treated with
      either a covered stent or surgery.

PMID- 18830067
TI  - Cryptogenic stroke and patent foramen ovale.
AB  - PURPOSE OF REVIEW: Controversy surrounds the issue of patent foramen ovale (PFO),
      stroke, and secondary prevention strategies. Paradoxical embolism is usually a
      presumed diagnosis, incidental PFOs are common, and treatment options have not
      been well compared. RECENT FINDINGS: Paradoxical embolism occurs at any age. The
      most likely potentiator of stroke risk in patients with cryptogenic stroke and
      PFO is a concomitant atrial septal aneurysm. PFO size, degree of shunting, and a
      coexisting hypercoagulable state may be additional risk factors. In addition to
      deep lower extremity veins, superficial and pelvic veins are increasingly
      identified as sources of embolism. Treatment options include antiplatelet agents,
      anticoagulants, surgical closure, or percutaneous closure devices. Recent studies
      have provided comparative data of different PFO closure devices. SUMMARY:
      Strategies for distinguishing incidental PFOs from pathogenic ones in cryptogenic
      stroke patients and for identifying patients at high risk of recurrence are
      needed. Off-label implantation of non-PFO closure devices in trial-eligible
      patients continues. Participation in ongoing, randomized clinical trials
      comparing closure devices with medical management is recommended by the Food and
      Drug Administration and professional societies. The trials will clarify if the
      risks of invasive endovascular device placement are outweighed by a long-term
      reduction in recurrent vascular events.

PMID- 18830068
TI  - Pulmonary arterial hypertension in adults with congenital heart disease: distinct
      differences from other causes of pulmonary arterial hypertension and management
      implications.
AB  - PURPOSE OF REVIEW: To present the available data on pathophysiology, clinical
      presentation, prognosis, and especially management strategies for adult patients
      with congenital heart disease (CHD) and pulmonary arterial hypertension (PAH).
      Particular emphasis is placed on differences between other types of PAH and CHD
      related PAH, in which clinical presentation and management relate to a
      constellation of factors, both pulmonary and cardiac. RECENT FINDINGS: Pulmonary
      vascular disease in adults with CHD and especially its extreme expression, the
      Eisenmenger syndrome, is a chronic disease with slow progression, leading to
      multiorgan failure and death, decades after its first clinical presentation. In
      the last few years, oral advanced therapies for PAH have emerged and are
      considered for mono or combination therapy for CHD, though the evidence is
      limited. Supportive care and prevention of complications seem to be at least as
      important in the overall care of these patients. SUMMARY: Although new advanced
      therapies hold promise in PAH secondary to CHD, long-term data are clearly
      needed. Advanced therapies should be considered when other causes of functional
      limitation, such as iron deficiency, have been first addressed. Expertise in CHD
      as well as PAH is essential for providing adequate care for this patient group
      with a unique pathophysiology.

PMID- 18830069
TI  - Chronic thromboembolic pulmonary hypertension: an updated review.
AB  - PURPOSE OF REVIEW: Venous thromboembolism is a spectrum of disease comprising
      deep vein thrombosis, thrombus in transit, acute pulmonary embolism, and chronic
      thromboembolic pulmonary hypertension (CTEPH) as a rare and late possible
      sequela. RECENT FINDINGS: On the basis of a prospective long-term study, the
      incidence of CTEPH is estimated at 3.8% within 2 years of all patients surviving
      an episode of symptomatic idiopathic pulmonary embolism. Young age, a large
      perfusion defect, and idiopathic clinical presentation are associated with a
      higher probability of CTEPH. Current pathophysiological concepts suggest a
      misguided thrombus resolution process that is triggered by infection,
      inflammation, autoimmunity, and malignancy. Diagnosis and therapy of CTEPH are
      interdisciplinary achievements and nowadays still based on a positive lung
      perfusion scan and for assessment of operability on a classical pulmonary
      angiography. Treatment of choice is surgical pulmonary endarterectomy of the
      pulmonary obstructions, which leads to restoration of normal pulmonary
      hemodynamics at rest in nearly 80% of patients. In expert centers, surgical
      mortality is under 10%. SUMMARY: CTEPH has emerged as a 'dual' pulmonary vascular
      disorder with major vessel vascular remodeling of thrombus organization, combined
      with a small vessel pulmonary arteriopathy that is a target for classic
      vasodilator treatments.

PMID- 18830070
TI  - Predicting outcomes in cardiac surgery: risk stratification matters?
AB  - PURPOSE OF REVIEW: To illustrate the limitations of predictive risk models in
      cardiac surgery, highlight the difficulty in interpreting risk-adjusted outcome
      analysis and discuss the challenges of making clinical decisions based on risk
      predictions, particularly in high-risk patients. RECENT FINDINGS: Predictive risk
      models developed after logistic regression or other complex statistical analysis
      are commonly perceived as rigorous means to determine risk-adjusted mortality in
      cardiac surgery. However, the discrimination provided by those predictive models
      is barely better than clinical judgment. Moreover, validation studies of those
      models show that their calibration is inconsistent, limiting their application
      for comparisons between different patient cohorts. Recent data also show that,
      without a reasonable overlap of case-mix distributions, apparently calibrated
      models used for risk-adjusted outcome analysis may lead to inaccurate side-by
      side comparisons of provider performance. Finally, most predictive models
      overestimate risk, particularly in the high-risk patients. SUMMARY: Failure to
      account for many biological and procedural variables and for the constantly
      evolving practice of surgery and perioperative medicine likely contributes to the
      modest predictive performance of risk models in cardiac surgery. Consequently,
      those models should have limited input in the analysis of provider performance
      and in the decision to accept or deny surgery to the high-risk patients.

PMID- 18830071
TI  - Intraoperative coronary graft assessment.
AB  - PURPOSE OF REVIEW: Intraoperative graft assessment in coronary artery bypass
      grafting is infrequently performed. Nevertheless, studies show an immediate graft
      closure rate of 5-9% and a 1-year closure rate of 20-30%. RECENT FINDINGS:
      Coronary angiography is the 'gold standard' for graft assessment yet has been
      seldom employed because of logistical problems and image quality. Two methods,
      transit time flow measurement and intraoperative fluorescence imaging are simple,
      safe, and expeditious. Intraoperative graft failure detection rates of 2-5% have
      been reported. SUMMARY: Early graft occlusion occurs frequently after coronary
      artery bypass grafting. Two relatively simple but underutilized methods of
      intraoperative graft assessment have been shown to be predictive of graft
      failure. Wider use of these techniques as well as wider availability of hybrid
      operating rooms, which will allow intraoperative coronary angiography, may reduce
      graft failure.

PMID- 18830072
TI  - Off-pump coronary bypass surgery for high-risk patients: only in expert centers?
AB  - PURPOSE OF REVIEW: Off-pump coronary artery bypass (OPCAB) grafting has been
      increasingly adopted in an effort to prevent deleterious effects of
      cardiopulmonary bypass, including the associated inflammatory response, global
      myocardial ischemia and the risks of aortic manipulation. In many studies, the
      greatest benefit of OPCAB has been in high-risk patients. This review will
      summarize the recent literature examining outcomes of OPCAB versus on-pump
      coronary artery bypass in high-risk subgroups, and will examine the safety of
      routine application of OPCAB in these patients. RECENT FINDINGS: Prospective
      randomized trials have shown that in comparison to on-pump coronary artery
      bypass, OPCAB reduces perioperative morbidity, but have failed to show a
      mortality benefit, owing to small sample sizes. However, numerous large
      retrospective series and meta-analyses have demonstrated a reduction in risk
      adjusted mortality and morbidity with respect to the following outcomes: stroke,
      pulmonary function, renal function, atrial fibrillation, need for early
      reoperation, blood transfusion requirements, length of ICU and hospital stay, and
      hospital costs. An even greater benefit has been seen in the following high-risk
      patients: those with acute myocardial infarction, left ventricular dysfunction,
      previous history of stroke, renal insufficiency, women, elderly patients, and
      those undergoing reoperations. SUMMARY: Risk-adjusted outcomes are superior after
      OPCAB versus on-pump coronary artery bypass for mortality and numerous morbidity
      endpoints. This benefit is most easily demonstrated in high-risk patient
      populations.

PMID- 18830073
TI  - Cardiocerebral resuscitation: a better approach to cardiac arrest.
AB  - PURPOSE OF REVIEW: To present a new approach to patients with cardiac arrest that
      improves neurologically normal survival. It is called cardiocerebral
      resuscitation (CCR), rather than cardiopulmonary resuscitation, as the major goal
      in cardiac arrest is to resuscitate the heart and the brain. CCR has three
      components: continuous chest compressions cardiopulmonary resuscitation for
      bystanders; a different Advanced Cardiac Life Support (ACLS) algorithm for
      Emergency Medical System; and a recently added aggressive postresuscitation care
      for resuscitated but comatose patients that includes therapeutic hypothermia and
      early catheterization/intervention. RECENT FINDINGS: Kellum et al. instituted the
      first two components of CCR in rural Wisconsin in 2004. In the subgroup of
      patients with a witnessed cardiac arrest and a shockable rhythm they found that
      neurological intact survival at hospital discharge was 15% the preceding 3 years,
      when the 2000 Guidelines were being followed, but 40% for the 3 years during CCR.
      Bobrow et al. instituted CCR for out-of-hospital cardiac arrest in metropolitan
      areas of Arizona and found a greater than 300% improvement (4.7-17.6%) in
      survival to hospital discharge of this subgroup of patients. SUMMARY: CCR
      improves survival of patients with cardiac arrest.

PMID- 18830074
TI  - Time to coronary angiography in patients with non-ST-segment elevation acute
      coronary syndrome: how fast should patients go to the catheterization laboratory?
AB  - PURPOSE OF REVIEW: This review describes available data on the optimal timing of
      an early invasive strategy in patients with high-risk non-ST-segment elevation
      acute coronary syndromes, along with challenges with type of studies. We also
      discuss the implication of timing in the overall management of the non-ST-segment
      elevation acute coronary syndrome patients. RECENT FINDINGS: The issue of timing
      of the coronary angiography has been addressed mainly with observational
      analyses. The only, small, randomized clinical trial, the Intracoronary Stenting
      With Antithrombotic Regimen Cooling-Off, indicated a superiority of an expedited
      approach compared with a much deferred angiography. A recent observational
      analysis adopting special statistical methodologies confirmed the finding of the
      Intracoronary Stenting With Antithrombotic Regimen Cooling-Off trial in patients
      undergoing an early invasive strategy in the first 48 h of presentation. SUMMARY:
      Current evidence is not sufficient to recommend the use of a routine expedite
      invasive strategy but suggests that it may be a viable approach.

PMID- 18830075
TI  - Distribution of body fat and risk of coronary heart disease in men and women.
AB  - PURPOSE OF REVIEW: Earlier studies investigating the risk of developing coronary
      heart disease in relation to body fat distribution showed inconsistent results,
      and any sex-related difference in disease risk has not been adequately examined.
      This review aims to assess current findings on the prospective association
      between body fat distribution measures and coronary heart disease in men and
      women. RECENT FINDINGS: Current epidemiologic evidence suggests that waist
      circumference and waist-hip ratio, as indicators of abdominal adiposity, are
      positively related to coronary heart disease in men and women independently of
      body mass index and conventional coronary heart disease risk factors. But the
      magnitude and shape of the associations for these abdominal adiposity indices
      varied with adjustments for mediating and confounding factors. Interestingly, hip
      waist circumference was inversely associated with coronary heart disease after
      adjusting for waist circumference. Because waist and hips are positively
      correlated but have separate and opposite associations with coronary disease,
      using waist circumference alone may provide underestimated risk estimate if hip
      girth is not accounted for in the calculation of this risk. SUMMARY: For adipose
      tissue distribution assessment to be clinically useful, the ideal adiposity
      phenotype should provide a single risk estimate that captures the separate
      'effects' of abdominal and peripheral adiposity. Although far from perfect, waist
      hip ratio may capture separate effects of central and peripheral adiposity. This
      simple and inexpensive measure could be used to help improve coronary heart
      disease risk assessment.

PMID- 18830077
TI  - Increased mortality, morbidity, and cost associated with red blood cell
      transfusion after cardiac surgery.
AB  - PURPOSE OF REVIEW: Literature since 2006 was reviewed to identify the harms and
      costs of red blood cell (RBC) transfusion. RECENT FINDINGS: Several studies, in
      people having various cardiac surgery operations, found strong associations of
      RBC transfusion with mortality and postoperative morbidity. The effect on
      mortality was strongest close to the time of operation but extended to 5 years.
      Morbidity outcomes included serious wound and systemic infections, renal failure,
      prolonged ventilation, low cardiac index, myocardial infarction, and stroke. RBC
      transfusion was also strongly associated with increased cardiac intensive care
      unit and ward postoperative stay, and hence, increased cost of admission;
      available studies did not consider all resources used and the associated costs.
      SUMMARY: The harms of RBC transfusion have potentially serious and long-term
      consequences for patients and are costly for health services. This evidence
      should shift clinicians' equipoise towards more restrictive transfusion practice.
      The immediate aim should be to avoid transfusing a small number of RBC units for
      general malaise attributed to anaemia, a practice that appears to occur in about
      50% of transfused patients. Randomized trials comparing restrictive and liberal
      transfusion triggers are urgently needed to directly compare the benefits and
      harms from RBC transfusion.

PMID- 18830076
TI  - Optimal imaging strategies to assess coronary blood flow and risk for patients
      with coronary artery disease.
AB  - PURPOSE OF REVIEW: This review is meant as a balanced summary of the current
      state of cardiac magnetic resonance (CMR) perfusion imaging in assessing
      alterations in myocardial blood flow due to coronary artery disease (CAD). We aim
      to provide first an accessible technical overview of first-pass CMR perfusion
      imaging and contrast it with other conventional perfusion imaging modalities, and
      then address the potential advantages of CMR for a qualitative assessment of
      perfusion defects, as well as quantitative blood flow measurements. Most recent
      results from clinical trials on the utility of CMR perfusion and novel directions
      will be explored. RECENT FINDINGS: Recent results of the first multicenter
      multivendor CMR perfusion study demonstrated superior diagnostic utility in
      detecting CAD by CMR compared with conventional nuclear single-photon emission
      computed tomography. Several large clinical trials provide additional evidence
      indicating the strong prognostic implications when CMR perfusion was performed in
      a clinical setting in patients with an intermediate clinical likelihood of CAD. A
      negative adenosine stress CMR perfusion study conferred a favorable 3-year
      prognosis towards nonfatal myocardial infarction or cardiac death. SUMMARY: CMR
      perfusion imaging during the first pass of gadolinium-based contrast agents has
      undergone many technical improvements and levels of clinical validation. Rapidly
      increasing clinical use worldwide over the last years in diagnosing chest pain
      syndromes supports the role of CMR in a comprehensive and efficient noninvasive
      assessment of altered myocardial physiology in CAD.

PMID- 18830078
TI  - Reperfusion strategies in acute ST-segment elevation myocardial infarction.
AB  - PURPOSE OF REVIEW: Chronic heart disease is the leading cause of death in the
      United States, and coronary artery disease constitutes the number one cause among
      them. ST-segment elevation myocardial infarction comprises a large number of
      events per year in the United States. It is important to develop an integrated
      framework of reperfusion strategies to minimize ischemia among these patients.
      The objective of this review is to outline available reperfusion options, which
      can then form an evidence-based approach to implementing complementary
      pharmacologic and mechanical strategies that can enhance timely and effective
      coronary reperfusion. RECENT FINDINGS: The updated American College of
      Cardiology/American Heart Association clinical practice guidelines espouse the
      important goal of facilitating rapid recognition and treatment of patients who
      present acutely with ST-segment elevation myocardial infarction so that door-to
      needle (or the first medical contact-to-needle) time for initiation of
      fibrinolytic therapy can be achieved within 30 min or door-to-balloon (or the
      first medical contact-to-balloon) time for primary percutaneous coronary
      intervention can be achieved within 90 min. SUMMARY: In conclusion, whatever
      reperfusion strategy is adopted, the ultimate objective should be to obtain
      prompt and effective reperfusion of ischemic myocardium as early as possible. The
      most efficacious and safe strategy for the treatment of ST-segment elevation
      myocardial infarction patients involves an integrated approach of highly
      organized networks to enhance the availability and use of primary percutaneous
      coronary intervention and to promote the selective use of fibrinolytic therapy,
      especially prehospital fibrinolysis, when primary percutaneous coronary
      intervention is not immediately available.

PMID- 18830079
TI  - Advances in molecular imaging of atherosclerotic vascular disease.
AB  - PURPOSE OF REVIEW: Molecular imaging aims to illuminate vital molecular and
      cellular aspects of disease in vivo, and is rapidly translating into the clinical
      arena. Advantages of this field include enabling serial biological studies in
      living subjects, assessment of pharmaceutical efficacy, and in-vivo
      characterization of clinical diseases. Here we present recent exciting advances
      in molecular imaging of atherosclerotic vascular disease. RECENT FINDINGS:
      Atherosclerosis molecular imaging approaches are now available for magnetic
      resonance, nuclear, computed tomography, ultrasound, and near-infrared
      fluorescence imaging. Advances in agent synthesis and detection technology are
      now enabling in-vivo imaging of endothelial cell activation, macrophages,
      cellular metabolism, protease activity, apoptosis, and osteogenic activity.
      Several agents show clinical utility for the detection of high-risk plaques.
      SUMMARY: Molecular imaging is actively unraveling the biological basis of
      atherosclerosis in living subjects. In the near-term, molecular imaging will play
      an important role in assessing novel atherosclerosis pharmacotherapies in
      clinical trials. Longer term, molecular imaging should enable accurate
      identification of high-risk plaques responsible for myocardial infarction,
      stroke, and ischemic limbs.

PMID- 18830080
TI  - A customized genetic approach to the number one killer: coronary artery disease.
AB  - PURPOSE OF REVIEW: To review the evidence supporting genetic predisposition to
      coronary artery disease (CAD). Secondly, to elucidate the barriers precluding the
      identification of genes responsible for CAD. Thirdly, to indicate the new
      technology now available to overcome these barriers and summarize current
      progress. RECENT FINDINGS: Evidence strongly supports that 50% of susceptibility
      to CAD is genetic. Prevention of CAD requires comprehensive genetic and risk
      factor modification. Technology to perform genome-wide association studies became
      available in 2005, namely, the microarrays with 500,000 and 1 million single
      nucleotide polymorphisms as DNA markers for high-throughput genotyping to
      determine gene frequencies in large datasets of cases and controls. The first
      genetic variant, 9p21, for CAD was identified in the Ottawa Heart Genomic study.
      This is not only a genetic risk factor but also independent of other known risk
      factors for CAD. 9p21 was subsequently confirmed as a risk variant in several
      other independent studies involving 64 000 Caucasians. 9p21 increases the risk of
      CAD by 40% and 20% in heterozygous or homozygous forms respectively. It occurs in
      75% of Caucasians, and has recently been confirmed in several other ethnic
      groups. SUMMARY: Thus, identification of predisposition to CAD is well underway
      with genome-wide association studies and the first common genetic risk variant,
      9p21, has been identified.

PMID- 18830081
TI  - Cardiac resynchronization therapy: dyssynchrony imaging from a heart failure
      perspective.
AB  - PURPOSE OF REVIEW: To review the evidence for and against imaging as a means of
      selecting patients for cardiac resynchronization therapy (CRT). RECENT FINDINGS:
      There is no evidence that either the QRS interval on the surface ECG or
      dyssynchrony measured by imaging is of any practical value in predicting the
      clinical response to CRT in patients with a dilated and dysfunctional left
      ventricle. Careful assessment of the patient, so that therapy can be logically
      aligned with treatment goals, such as improving symptoms or prognosis, is the
      only useful method for selecting patients. Simple clinical evaluation may be as
      effective as, or more effective than, more complex assessments in predicting
      treatment benefits. Patients with a low blood pressure and moderate functional
      mitral regurgitation might benefit more, in absolute terms, from CRT. The
      benefits of adding a defibrillator to CRT are modest and, for many patients,
      uncertain. SUMMARY: Echocardiography, which was supposed to facilitate the
      introduction of CRT, may have become the greatest barrier to its appropriate
      implementation. Cardiac dyssynchrony, measured by echocardiography prior to
      implantation, may not be the substrate for the effects of CRT.

PMID- 18830082
TI  - Bibliography. Current world literature. Diseases of the aorta, pulmonary, and
      peripheral vessels.

PMID- 18830083
TI  - Screen detection and the WHO stepwise approach to the prevalence and risk factors
      of arterial hypertension in Kinshasa.
AB  - BACKGROUND: The trend of hypertension and other risk factors of cardiovascular
      disease is changing because of epidemiological, demographic and nutritional
      transitions in sub-Saharan Africa. OBJECTIVES: The aim of this study is to
      determine the prevalence and risk factors of arterial hypertension in the
      Kinshasa region, Democratic Republic of Congo (DRC). DESIGN AND METHODS: Data
      were collected from random sample cross-sectional surveys of adult black Africans
      from Kinshasa, with the help of a structured questionnaire, physical examinations
      and blood samples, using the World Health Organisation (WHO) stepwise approach.
      Sex, age, place of residence (urban versus rural), psychosocial risk factors
      (socioeconomic status, stress), overweight status (BMI: 25-29.9 kg/m), general
      obesity (BMI: >or=30 kg/m), abdominal obesity (waist circumference: >or=94 cm)
      and diabetes mellitus were considered to be the potential risk factors for screen
      detected hypertension. RESULTS: The weighted prevalences of hypertension,
      diabetes mellitus, overweight status, general obesity and abdominal obesity were
      15.2, 140.2, 13.5, 4.8 and 7.5%, respectively. Blood pressure and the proportion
      of participants with hypertension increased with age and BMI group in the
      population, for both men and women. Age, rural residence, low socioeconomic
      status, high socioeconomic status, general obesity and abdominal obesity were the
      risk factors for hypertension. Women aged 55 years and above had higher levels of
      blood pressure and hypertension than men. CONCLUSION: Absolute levels of
      hypertension, all types of obesity and diabetes mellitus are high risk factors in
      the army camps and semiurban extension cities; general obesity and abdominal
      obesity are the risk factors for detectable hypertension. Effective control of
      general obesity and abdominal obesity and psychosocial strategies that target
      both semirural and urban areas of the Kinshasa region have the potential to
      prevent much premature cardiovascular disease.

PMID- 18830084
TI  - Lipid-lowering treatment for all could substantially reduce the burden of
      macrovascular complications of diabetes patients in the Netherlands.
AB  - BACKGROUND: We aimed to quantify the potential health benefits of increased use
      of lipid-lowering treatment (LLT), according to current guidelines, for the Dutch
      diabetes population. DESIGN: Simulation study. METHODS: We compared the long-term
      health outcomes for a scenario in which all diabetes patients received LLT to
      those in a 'current practice' scenario, in which 28% received LLT. The model
      reflected the Dutch diabetes population 40-80 years of age, in 2003. Sensitivity
      analyses were performed, using more conservative assumptions. RESULTS: Over the
      lifetime, LLT for all diabetes patients reduced the expected cumulative
      incidences of coronary heart disease (CHD) and stroke by, respectively, 6 and 9%.
      Average life expectancy of Dutch diabetes patients would increase by 0.33 years,
      ranging from 0.14 years for patients aged 70-79 years, to 0.84 years for patients
      aged 40-49 years at the start of the simulation. Life-long treatment for patients
      aged 50-59 contributed most to the life years gained (55,000 out of 146,000).
      With reduced effectiveness of LLT and fewer patients starting LLT, the cumulative
      incidences of both CHD and stroke would decrease by approximately 2%. The number
      needed to treat to prevent one incident case of cardiovascular disease over
      lifetime was 20 for CHD and 44 for stroke. CONCLUSION: This simulation study
      shows that increased use of LLT can substantially reduce the expected future
      burden of CHD and stroke in the Dutch diabetes population.

PMID- 18830085
TI  - Contribution of patient and physician factors to cardiac rehabilitation
      enrollment: a prospective multilevel study.
AB  - BACKGROUND: Cardiac rehabilitation (CR) is an established means of reducing
      mortality, yet is grossly underutilized. This is due to both health system and
      patient-level factors; issues that have yet to be investigated concurrently. This
      study utilized a hierarchical design to examine physician and patient-level
      factors affecting verified CR enrollment. DESIGN: A prospective multisite study,
      using a multilevel design of 1490 coronary artery disease outpatients nested
      within 97 Ontario cardiology practices (mean 15 per cardiologist). METHODS:
      Cardiologists completed a survey regarding CR attitudes. Outpatients were
      surveyed prospectively to assess factors affecting CR enrollment. Patients were
      mailed a follow-up survey 9 months later to self-report CR enrollment. This was
      verified with 40 CR sites. RESULTS: Five hundred and fifty (43.4%) outpatients
      were referred, and 469 (37.0%) enrolled in CR. In mixed logistic regression
      analyses, factors affecting verified CR enrollment were greater strength of
      physician endorsement (P=0.005), shorter distance to CR (P=0.001), being married
      (P=0.01), and fewer perceived CR barriers (P=0.03). CONCLUSION: Both physician
      and patient factors play a part in CR enrollment. Patient CR barriers should be
      addressed during referral discussions, and reasons why physicians fail to
      uniformly endorse CR exploration. Although distance to CR was related to patient
      enrollment patterns, greater access to home-based CR services should be provided.

PMID- 18830086
TI  - Symptoms of fatigue and depression in ischemic heart disease are driven by
      personality characteristics rather than disease stage: a comparison of CAD and
      CHF patients.
AB  - BACKGROUND: Symptoms of fatigue and depression are prevalent across stages of
      ischemic heart disease (IHD). We examined (i) the effect of both the IHD stage
      and type-D personality on fatigue and depressive symptoms at 12-month follow-up,
      and (ii) whether the effect of type-D personality on these symptoms is moderated
      by IHD stage. METHODS: Two different samples of patients were included to
      represent IHD stage: 401 percutaneous coronary intervention patients (early-stage
      IHD) and 105 ischemic chronic heart failure patients (end-stage IHD) completed
      the DS14 Type-D Scale at baseline. Logistic regression analysis was used to
      examine the impact of IHD stage and type-D personality on fatigue and depression
      at follow-up. RESULTS: Disease stage was neither associated with symptoms of
      fatigue (P=0.99) nor depression (P=0.29) at 12 months. In contrast, type-D
      personality was shown to predict both symptoms of fatigue [odds ratio (OR)=2.96;
      95% confidence interval (CI): 1.92-4.58, P<0.001] and depression (OR=4.91; 95%
      CI: 3.16-7.65, P<0.001) at follow-up; the effect of type-D personality on these
      symptoms was not moderated by disease stage. In multivariable analysis, type-D
      remained a significant predictor of symptoms of fatigue (OR=3.14; 95% CI: 1.98
      4.99, P<0.001) and depression (OR=5.90; 95% CI: 3.60-9.67, P<0.001), also after
      controlling for symptom levels at baseline. CONCLUSION: Type-D personality but
      not disease stage predicted symptoms of fatigue and depression at 12-month follow
      up.

PMID- 18830087
TI  - Adherence to a Mediterranean-type diet and reduced prevalence of clustered
      cardiovascular risk factors in a cohort of 3,204 high-risk patients.
AB  - BACKGROUND: The Mediterranean food pattern (MeDiet) has been suggested to have
      beneficial effects on cardiovascular risk factors. Scarcity of assessment of this
      effect on large samples of patients at high risk is, however, observed. Our
      objective was to estimate the association between adherence to MeDiet and the
      prevalence of risk factors in 3,204 asymptomatic high-risk patients. DESIGN:
      Cross-sectional assessment of baseline characteristics of participants in a
      primary prevention trial. METHODS: Participants were assessed by their usual
      primary-care physicians to ascertain the prevalence of diet-related
      cardiovascular risk factors (diabetes, hypertension, dyslipidemia, or obesity)
      using standard diagnostic criteria. A dietitian interviewed each participant to
      obtain a 14-point score measuring the degree of adherence to MeDiet. RESULTS:
      Adherence to MeDiet was inversely associated with individual risk factors and,
      above all, with the clustering of them. The multivariate adjusted odds ratio to
      present simultaneously the four risk factors for those above the median value of
      the MeDiet score was 0.67 (95% confidence interval: 0.53-0.85). The multivariate
      odds ratios for successive categories of adherence to MeDiet were 1 (ref.), 1.03,
      0.85, 0.70 and 0.54 (P for trend <0.001). CONCLUSION: Following a MeDiet was
      inversely associated with the clustering of hypertension, diabetes, obesity, and
      hypercholesterolemia among high-risk patients.

PMID- 18830089
TI  - Introduction: professionals in dialogue: sharing insights and knowledge into gout
      management.

PMID- 18830090
TI  - How PCP education can impact gout management: the gout essentials.

PMID- 18830091
TI  - Gout: what primary care physicians want to know.
AB  - Gout is an inflammatory arthritis that has been recognized since ancient times.
      It is the most common type of inflammatory arthritis in men. Despite these facts,
      no new advances have been made in the diagnosis and treatment of gout for over 50
      years. Since there have been no new advances and the condition has been
      recognized for so many centuries, the diagnosis and treatment of gout has not
      elicited interest in learning more about the disease. Thus, managing gout is a
      challenge for the clinician caring for the gout patient. Rheumatologists should
      be the educators of primary care physicians (PCPs) about the diagnosis and
      optimal treatment of gout. A recent educational meeting was held, the
      Hyperuricemia and Gout Summit, in which a panel of leading rheumatologists
      educated PCPs about gout management through didactic presentations and breakout
      sessions focused on case studies. At this meeting, the PCPs discussed some of
      their key challenges in managing gout in their practice. This article reviews
      current recommendations for the diagnosis and treatment of gout, using
      educational examples from the Hyperuricemia and Gout Summit. It also highlights
      the importance of providing practical recommendations to PCPs to improve the
      standard of care for gout in the primary care setting.

PMID- 18830092
TI  - Gout: an evidence-based review.

PMID- 18830093
TI  - Interatrial shunt detected in coronary computed tomography angiography:
      differential features of a patent foramen ovale and an atrial septal defect.
AB  - OBJECTIVE: To determine differential findings of patent foramen ovales (PFOs) and
      atrial septal defects (ASDs) demonstrating interatrial shunting on coronary
      computed tomography (CT) angiography. METHODS: We retrospectively analyzed 15
      cases of patients demonstrating a contrast jet from the left to the right atrium
      on CT and interatrial shunting on echocardiography. According to the
      echocardiography results, patients were divided into PFO (n = 10) or ASD (n = 5)
      groups. The contrast jet direction and atrial septum appearance on CT were
      compared between the 2 groups. RESULTS: The PFO group had a contrast jet flowing
      toward the inferior vena cava, and the atrial septum appeared channel-like. The
      ASD group had a contrast jet flowing perpendicular to the atrial septum in all
      but one of the patients, and the atrial septum appeared as a membrane with a
      hole. CONCLUSIONS: Atrial septal defects and PFOs can be differentiated using the
      characteristic direction of the contrast jet from the left to right atrium and
      the appearance of the atrial septum on coronary CT angiography.

PMID- 18830094
TI  - Dose reduction and image quality assessment in 64-detector row computed
      tomography of the coronary arteries using an automatic exposure control system.
AB  - OBJECTIVE: To evaluate dose reduction and image quality in coronary 64-slice
      multidetector computed tomography using an automatic exposure control system
      (AECs). METHODS: A total of 101 patients were divided into 4 groups. Tube current
      was 600 and 800 mAs in groups A and B and adapted at 600 and 800 quality
      reference mAs using an AECs in groups C and D. Effective dose and organ
      equivalent dose were evaluated. Image noise was quantified as standard deviation
      of air-space attenuation. Two observers assessed technical adequacy and image
      quality using a 4-point scale. RESULTS: Effective dose ranged from 8.6 mSv (group
      C) to 15 mSv (group B) with significant dose reduction for examinations performed
      at 600 mAs (21.7%) and 800 mAs (29.4%). Contribution of organ-equivalent doses
      showed higher exposure for lungs (42%) and breast (22%). Noise was significantly
      higher in groups studied with AECs. Larger coronary segments resulted in higher
      image quality scores without differences between groups. CONCLUSION: Automatic
      exposure control systems provides images of diagnostic quality with substantial
      dose reduction.

PMID- 18830095
TI  - Cardiovascular Behcet disease: the variable findings of rare complications with
      CT angiography and conventional angiography and its interventional management.
AB  - Unusual radiological manifestations of rare complications of cardiovascular
      Behcet disease (BD) are the following: (a) aneurysm and (b) occlusion in the
      aorta and its major branches, (c) pseudoaneurysms on the aortic root and coronary
      artery, and recurrent valvular dehiscence in the heart, (d) venous thrombosis in
      the deep and superficial venous system and vena cava. The initial exact diagnosis
      of cardiovascular BD has been extremely difficult for these rare complicated
      findings, especially in the absence of the florid clinical manifestations of BD.
      Radiologist should be aware of possibility of cardiovascular BD via familiarity
      with its rare imaging features, including computed tomographic angiography (and
      its 3-dimensional reconstructed images), conventional angiography, and with the
      clinical characteristics of BD because of high mortality of cardiovascular BD.

PMID- 18830096
TI  - Four-detector row computed tomographic angiography in the evaluation of
      infrarenal aorta and peripheral arterial occlusive disease: influence of contrast
      medium concentration.
AB  - PURPOSE: To prospectively compare the diagnostic accuracy and quality of vascular
      enhancement of 2 contrast agents with different iodine concentrations in 4
      detector row computed tomographic angiography of abdominal aorta and lower
      extremity arteries. MATERIALS AND METHODS: Forty consecutive patients with
      peripheral arterial occlusive disease referred for conventional angiography
      (digital subtraction angiography [DSA]) of the lower extremity were prospectively
      enrolled in the study and underwent multidetector row computed tomographic
      angiography (CTA) receiving either 90 mL of iomeprol 400 (Iomeron 400, group A;
      Bracco Imaging S.p.A., Milan, Italy) or 120 mL of iomeprol 300 (Iomeron 300,
      group B; Bracco Imaging). Resultant images, both axial, maximum intensity
      projection, multiplanar reformatted, and volume-rendered 3-dimensional images,
      were independently evaluated by 2 clinically competent and experienced blinded
      radiologists for the presence of stenotic and occluded arterial segments using
      DSA as the standard of reference. Computed tomographic images were also evaluated
      quantitatively for maximum arterial and venous enhancement, and qualitatively for
      vascular opacification, venous overlap, and diagnostic efficacy. Quantitative and
      qualitative results of the 2 study agent groups were statistically compared. Both
      contrast media were evaluated for safety and tolerability. RESULTS: From 760
      segments, 722 arterial segments were effectively evaluated in the comparative
      analysis of CTA and DSA. In the evaluation of significant stenoses (>70%) and
      occluded segments, multidetector row CTA obtained a sensitivity, specificity, and
      accuracy of 97.1%, 96%, and 96.3%, and 98.9%, 100%, and 99%, respectively.
      Iomeprol 400 demonstrated an increased arterial enhancement in aortoiliac and
      femoral districts in comparison to iomeprol 300 (mean increase in opacification,
      37.3 Hounsfield units) and a significant better qualitative assessment in the
      aortoiliac segments without an increase in venous opacification or the presence
      of venous overlap. No significant differences were found for sensitivity and
      specificity for the diagnosis of significant stenoses (>70%) and occluded
      segments. Both agents were well tolerated, and no adverse events were recorded.
      CONCLUSIONS: The use of a small volume of a high-concentration contrast material
      yielded higher arterial enhancement from the abdominal aorta down to the femoral
      arteries with absent or minimal venous overlap and without significant
      differences in diagnostic ability.

PMID- 18830097
TI  - Functional computed tomographic quantification of angiogenesis in rabbit VX2 soft
      tissue tumor before and after interventional therapy.
AB  - OBJECTIVE: Our purpose was to investigate the applicative value of multislice
      spiral computed tomography (CT) perfusion imaging on quantitative assessment of
      tumor angiogenesis before and after transcatheter arterial embolization and
      monitoring the early interventional therapeutic effect in malignant solid tumors.
      METHODS: Sixteen New Zealand white rabbits successfully implanted VX2 tumor in
      the unilateral proximal thigh were divided into 2 groups (8 per group) at random
      and performed conventional CT plain scan and perfusion scan 14 days after
      implantation and 3 days after interventional therapy, respectively. The values of
      blood flow (BF), blood volume (BV), mean transit time (MTT), and permeability
      surface area product (PS) in VX2 tumors and normal muscles were computed after
      intravenous bolus administration of iodinated contrast medium, and the
      differences among them were analyzed. Meanwhile, correlative analysis between
      perfusion parameters and microvessel density (MVD) counts and average optical
      density (AOD) of vascular endothelial growth factor (VEGF) was done. RESULTS:
      Before interventional therapy, the values of BF, BV, MTT, and PS of the VX2
      tumors in interventional group were 303.28 +/- 69.91 mL 100 g min, 7.02 +/- 3.10
      mL 100 g, 1.99 +/- 0.28 seconds, and 65.88 +/- 9.38 mL 100 g min, respectively.
      Compared with the parametric values of normal muscular tissues, there were
      significant differences among them (F values were 4285.82, 1867.46, 413.04, and
      698.42, respectively; P < 0.01). There were no significant differences of the
      above parametric values between the interventional group and the control group.
      Three days after interventional therapy, the values of BF, BV, MTT, and PS of the
      VX2 tumors in the interventional group were 7.53 +/- 2.37 mL 100 g min, 1.20 +/-
      0.23 mL 100 g, 3.29 +/- 0.57 seconds, 4.01 +/- 1.51 mL 100 g min, respectively.
      Compared with the parametric values of preinterventional therapy and the control
      group, there were significant differences among them (P < 0.01). In addition,
      there was a good positive correlation between BF, BV, PS, and MVD, and AOD of
      VEGF (r > 0.7, P < 0.05) in VX2 tumors; however, there was no significant
      correlation between MTT and MVD (P > 0.05), and there was significant negative
      correlation between MTT and AOD of VEGF (r = -0.78, P < 0.05). CONCLUSIONS:
      Multislice spiral CT perfusion imaging is a functional imaging technique that
      provides useful, quantitative assessment to tumor angiogenesis, blood perfusion,
      and vascular permeability, which can evaluate the early interventional
      therapeutic effect in malignant solid tumors invasively and accurately.

PMID- 18830098
TI  - Preaortic iliac confluence (marsupial vena cava): report of 4 cases.
AB  - Congenital anomalies of the inferior vena cava (IVC) can represent a difficult
      for abdominal surgeries, and the radiologist must be aware even of the less
      common of these anatomical variations. Preaortic iliac venous confluence, also
      known as marsupial vena cava, is a rare congenital anomaly of the development of
      the IVC in which the IVC or the left common iliac vein is located anterior to the
      aortic bifurcation or the right common iliac artery. We report 4 cases of
      marsupial vena cava detected on multidetector computed tomography examinations in
      asymptomatic patients and discuss that this congenital anomaly can be recognized
      more frequently with the use of this new technique based on thinner images.

PMID- 18830099
TI  - Left atrial calcifications: computed tomographic imaging findings of an unusual
      sign of rheumatic heart disease.
AB  - Left atrial wall calcifications are an extremely rare finding of unknown cause
      usually associated with rheumatic disease. Only a few case reports of this entity
      are found in the literature, mostly describing the findings on conventional chest
      radiography, echocardiography, and angiography. To the best of our knowledge,
      this is the first case documented with multislice computed tomography.

PMID- 18830100
TI  - Value of magnetic resonance imaging for the diagnosis of ovarian tumors: a
      review.
AB  - This article reviews the value of magnetic resonance imaging (MRI) for the
      diagnosis of ovarian tumors especially when ultrasonography is indeterminate.
      Although ultrasonography is the first imaging technique used to investigate
      suspected pelvic masses, it has a limited capacity for tissue characterization.
      In addition to morphological characteristics, many tissue parameters such as T1,
      T2, perfusion, and diffusion contribute to signal intensity, so MRI is able to
      identify various types of tissue contained in pelvic masses. Magnetic resonance
      imaging helps to locate large solid masses and to distinguish benign from
      malignant ovarian tumors, with an overall accuracy of 88% to 93% for the
      diagnosis of malignancy. The aims of this review are 3-fold. First, we review
      state-of-the-art and usual MRI techniques and published findings. Second, we
      recall the MR features most useful for assessing the main ovarian tumors.
      Finally, we discuss the relevance of various features for distinguishing between
      benign, borderline, and invasive ovarian tumors.

PMID- 18830101
TI  - Detection of hypervascular hepatocellular carcinoma with multidetector-row CT:
      single arterial-phase imaging with computer-assisted automatic bolus-tracking
      technique compared with double arterial-phase imaging.
AB  - PURPOSE: To compare single arterial-phase (SAP) computed tomography (CT) imaging
      with bolus tracking (BT) with double arterial-phase (DAP) CT imaging for
      detecting hypervascular hepatocellular carcinoma. MATERIALS AND METHODS: The DAP
      images were obtained at 25 (DAP-early) and 40 seconds (DAP-late) after the start
      of contrast material injection. All patients underwent SAP-BT imaging where
      images were obtained 10 seconds after the CT attenuation value of the aorta
      reached the threshold value of 120 Hounsfield unit (HU) in 29 (group 120-HU), 160
      HU in 30 (group 160-HU), and 200 HU in 32 patients (group 200-HU). Attenuation
      conspicuity with SAP-BT technique was compared with that with DAP technique using
      repeated-measures analysis of variance. Attenuation conspicuity and mean scan
      delays with SAP-BT images obtained with different threshold values were compared
      using analysis of variance. The sensitivities were compared using McNemar and
      Fisher exact tests. RESULTS: Within all groups, mean attenuation conspicuity with
      SAP-BT and DAP-late was significantly higher than that with DAP-early. Regarding
      SAP-BT, mean attenuation conspicuity in group 200-HU (42 +/- 18 HU) was
      significantly higher than those in groups 120-HU (23 +/- 11 HU) and 160-HU (25 +/
      11 HU). Mean scan delays for SAP-BT were 24.2 seconds in group-120 HU, 26.8
      seconds in group-160 HU, and 31.1 seconds in group-200 HU (P < 0.001). The mean
      sensitivity with SAP-BT technique in group 200-HU (92.7%) was significantly
      higher than those in groups 120-HU (72.4%) and 160-HU (71.1%). CONCLUSIONS:
      Single arterial-phase CT scanning with bolus tracking can be effectively used to
      detect hepatocellular carcinoma when a threshold value of 200 HU is used.

PMID- 18830102
TI  - Usefulness of computed tomography in differentiating transmural infarction from
      nontransmural ischemia of the small intestine in patients with acute mesenteric
      venous thrombosis.
AB  - OBJECTIVE: To determine computed tomographic findings that are helpful in
      differentiating transmural infarction from nontransmural ischemia in patients
      with mesenteric ischemia secondary to acute mesenteric venous thrombosis (MVT).
      METHODS: Twenty-seven patients with symptomatic acute MVT were categorized into 2
      groups: a transmural infarction (n = 13) and a nontransmural ischemia group (n =
      14) based on findings at surgery and clinical follow-up. Computed tomographic
      scans were retrospectively reviewed by the consensus of 2 radiologists. Computed
      tomographic findings were compared between the 2 groups using the Fisher exact
      and the independent sample t test. Multifactorial logistic regression analysis
      was performed to determine the best predictors for differentiating transmural
      infarction from nontransmural ischemia. RESULTS: Bowel segments with homogeneous
      enhancement (P = 0.001), decreased enhancement (P = 0.001), and indistinct outer
      margins (P = 0.006) were significantly more common in the transmural infarction
      group than in the nontransmural ischemia group. The differences in maximal lumen
      diameter (P = 0.027), extent of mesenteric haziness (P = 0.018), and amount of
      ascites (P = 0.035) were significant between the 2 groups. On multifactorial
      logistic regression analysis, decreased enhancement (P = 0.007) and maximal lumen
      diameter (P = 0.039) were independent significant variables in differentiating
      transmural infarction from nontransmural ischemia. CONCLUSIONS: In patients with
      acute MVT, computed tomography is valuable in differentiating transmural
      infarction from nontransmural ischemia.

PMID- 18830103
TI  - Liver lesion detection and characterization in patients with colorectal cancer: a
      comparison of low radiation dose non-enhanced PET/CT, contrast-enhanced PET/CT,
      and liver MRI.
AB  - OBJECTIVES: To compare low-radiation dose non-enhanced fluorine 18
      fluorodeoxyglucose (F-18 FDG) positron emission tomography (PET)/computed
      tomography (CT) (NE-PET/CT), contrast-enhanced fluorine 18 fluorodeoxyglucose
      PET/CT (CE-PET/CT), and gadolinium-enhanced liver magnetic resonance imaging
      (MRI) for the detection and characterization of liver lesions in patients with
      colorectal cancer (CRC). METHODS: In this retrospective review of imaging
      database of CRC patients with suspected liver metastases, 33 patients (22 men, 11
      women; mean age, 63 years) evaluated with low-radiation dose NE-PET/CT, CE
      PET/CT, and liver MRI were studied. The final diagnosis was established either by
      pathological examination or follow-up imaging over a period of at least 6 months
      for lesion stability or growth. The liver lesions were characterized on an
      ordinal scale of 0 to 6 (0 = absent, 1 = definitely benign, and 6 = definitely
      malignant). Receiver operating characteristic analysis was performed to compare
      performance of the 3 imaging methods. RESULTS: A total of 110 lesions were
      present on follow-up. The detection rate on low-radiation dose NE-PET/CT, CE
      PET/CT, and MRI was 73.6%, 90.9%, and 95.4%, respectively. Magnetic resonance
      imaging (P < 0.001) and CE-PET/CT (P < 0.001) had a higher detection rate than
      low-radiation dose NE-PET/CT. There was no significant statistical difference in
      lesion detection between MRI and CE-PET/CT (P = 0.11). The sensitivity,
      specificity, and accuracy for characterization of detected liver lesions on low
      radiation dose NE-PET/CT were 67%, 60%, and 66%, respectively; those on CE-PET/CT
      were 85%, 100%, and 86%, respectively; and those on MRI were 98%, 100%, and 98%,
      respectively. Comparative receiver operating characteristic analysis showed an
      area under curve of 0.74 for low-radiation dose NE-PET/CT, 0.86 for CE-PET/CT,
      and 0.97 for MRI. There were statistically significant differences in the
      accuracy of MRI, low-radiation dose NE-PET/CT, and CE-PET/CT for lesion
      characterization. CONCLUSIONS: When performing PET/CT, optimal detection and
      characterization of liver lesions require the use of a fused contrast-enhanced
      CT. Magnetic resonance imaging and CE-PET/CT have similar lesion detection rates.
      Magnetic resonance imaging is the best test for liver lesion characterization in
      patients with CRC.

PMID- 18830104
TI  - Radiological and clinical features of sarcomatoid hepatocellular carcinoma in 11
      cases.
AB  - OBJECTIVE: To evaluate the imaging and clinical findings of pathologically proven
      sarcomatoid hepatocellular carcinoma (HCC) in 11 cases. METHODS: We
      retrospectively reviewed the imaging findings and clinical features of 11
      patients with pathologically proven sarcomatoid HCC at 2 university-based
      tertiary institutions from July 1997 to June 2006. RESULTS: The most common gross
      morphologies of sarcomatoid HCC were massive expanding pattern (n = 6 [54%]) or
      multinodular confluent (n = 5 [46%]) with partial encapsulation (n = 9 [82%]).
      The most common enhancement pattern was peripheral enhancement with central
      necrosis (n = 8 [72%]) without a dominant dynamic pattern of enhancement. Six
      (54%) of 11 patients were positive for hepatitis B surface antigen or hepatitis C
      virus antibody. Only 1 patient (9%) had more than 500 ng/mL of preoperative serum
      alpha-fetoprotein. CONCLUSIONS: In a patient with low-level alpha-fetoprotein and
      no history of viral hepatitis, sarcomatoid HCC usually presents as a large mass
      with peripheral enhancement, central necrosis, variable enhancement of the solid
      portion with or without tumor capsule, and intrahepatic metastasis.

PMID- 18830105
TI  - Receiver operating characteristic analysis of diffusion-weighted magnetic
      resonance imaging in differentiating hepatic hemangioma from other hypervascular
      liver lesions.
AB  - PURPOSE: To evaluate the role of diffusion-weighted imaging in differentiating
      between hepatic hemangiomas, both typical and atypical, and other hypervascular
      liver lesions. METHODS: Retrospective review of 182 hypervascular liver lesions
      in 117 patients was performed. Diffusion and contrast-enhanced magnetic resonance
      imaging were performed using a 1.5-T unit. Imaging protocol consisted of T2
      weighted fast spin-echo images, breath-hold diffusion-weighted echo-planar
      images, and breath-hold unenhanced and contrast-enhanced T1-weighted 3
      dimensional fat-suppressed spoiled gradient-echo images in the arterial phase (20
      seconds) and portal venous phase (60 seconds). Signal intensity changes and
      apparent diffusion coefficient (ADC) values were evaluated for all lesions.
      Unpaired t test was used to compare the mean ADC values for different lesions,
      and statistical significance was set at P < 0.01. Receiver operating
      characteristic analysis was used to determine the accuracy of diffusion-weighted
      imaging in differentiating hemangiomas from other hypervascular liver lesions.
      RESULTS: Lesions included typical and atypical hemangioma (n = 38),
      hepatocellular carcinoma (HCC; n = 58), focal nodular hyperplasia (FNH; n = 22),
      and neuroendocrine tumor metastasis (NET; n = 64) with a mean tumor size of 5.3
      cm. Mean ADC value for hemangioma, HCC, FNH, and NET was 2.29 x 10(-3), 1.55 x
      10(-3), 1.65 x 10(-3), and 1.43 x 10(-3) mm2/s, respectively. There was a
      statistically significant difference in the ADC value of hemangioma compared with
      that of FNH (P < 0.001), HCC (P < 0.001), and NET (P < 0.001), respectively. The
      area under the receiver operating characteristic curve was 0.91. CONCLUSIONS:
      Diffusion-weighted magnetic resonance imaging and ADC maps can provide rapid
      quantifiable information to differentiate typical and atypical hemangiomas from
      other hypervascular liver lesions.

PMID- 18830106
TI  - Pancreatic cystic lesions: discrimination accuracy based on clinical data and
      high-resolution computed tomographic features.
AB  - OBJECTIVE: To determine the frequency of typical features of pancreatic cystic
      lesions on high-resolution computed tomography and the combination of features
      that best influences discrimination. METHODS: Ten computed tomography features of
      100 proven pancreatic cystic lesions were retrospectively tabulated by 2 blinded
      imagers. After final diagnosis was revealed, each lesion was categorized as
      typical or atypical. Stepwise multivariable logistic regression was used to
      determine which of 10 imaging and 4 clinical features significantly distinguished
      between benign and malignant lesions. RESULTS: There were 38 benign cysts and 62
      cystic tumors. Serous lesions presented with greater than 6 cysts (83%) and cysts
      of less than 2 cm (44%). Mucinous lesions presented with cysts of 2 cm or greater
      (82%) and less than 6 cysts (64%). Pseudocysts, serous, and mucinous lesions
      presented typically in 77%, 67%, and 64% of cases, respectively. The significant
      variables in classifying malignant lesions are pancreatitis history, cyst size,
      symptoms, and calcification pattern (area under the curve, 0.837). CONCLUSIONS:
      Four specific imaging and clinical features in combination best predict a
      malignant lesion.

PMID- 18830107
TI  - Detection and evaluation of pelvic lymph nodes in patients with gynecologic
      malignancies using body diffusion-weighted magnetic resonance imaging.
AB  - BACKGROUND: In this study, the potential in detecting and evaluating pelvic lymph
      node metastases on body diffusion-weighted (DW) images was evaluated in patients
      with gynecologic malignancies. METHODS: This study included 18 patients with
      gynecologic malignancy who underwent magnetic resonance imaging in the pelvis
      using a 1.5-T superconductive magnet. The identification of pelvic nodes on only
      T2-weighted (T2W) axial images and on DW axial images in addition to T2W axial
      images was examined and compared. Moreover, we measured and calculated a short
      axis diameter, a long-axis diameter, and a ratio of short- and long-axis diameter
      of nodes on the T2W images and the apparent diffusion coefficient (ADC) values of
      the nodes on the DW images. These results were compared with histopathologic
      results. RESULTS: First, 136 (40%) of 340 dissected nodes were identified on T2W
      images, and 249 (73%) of 340 dissected nodes were identified on DW images in
      addition to T2W images. Second, the differences in the short-axis diameter, the
      long-axis diameter, and the ratio of short- and long-axis diameter on T2W images
      between metastatic and nonmetastatic nodes were not significant. The differences
      in the ADC values between metastatic and nonmetastatic nodes were not
      significant. CONCLUSIONS: Body DW images are useful in detection of pelvic lymph
      nodes in patients with gynecologic malignancy. However, the measurement of ADC
      values does not contribute to a diagnosis of metastatic nodes.

PMID- 18830108
TI  - Solitary fibrous tumor of the liver: magnetic resonance imaging evaluation and
      treatment with transarterial chemoembolization.
AB  - Solitary fibrous tumor (SFT) is an uncommon neoplasm first described as a tumor
      of mesenchymal origin that rarely involves the liver. This report presents a rare
      case of unresectable SFT of the liver and documents the first use of
      transarterial chemoembolization in its treatment. Three sessions of
      chemoembolization were performed aiming to reduce the tumor size or at least
      stabilize it. Subsequent follow-up magnetic resonance imaging examinations were
      performed to assess imaging response to treatment. We recommend further studies
      to be done to assess both the use of transarterial chemoembolization in the
      treatment of unresectable SFT and the use of contrast-enhanced and diffusion
      weighted magnetic resonance imaging for assessment of the tumor response to
      treatment.

PMID- 18830109
TI  - Solitary littoral cell angioma of the spleen: computed tomography and magnetic
      resonance imaging features.
AB  - Littoral cell angioma is a rare primary vascular neoplasm of the spleen composed
      of blood-filled vascular channels. Typically, littoral cell angioma presents with
      splenomegaly caused by multiple small hypoattenuating nodules that show delayed
      enhancement. We report an unusual case of littoral cell angioma of the spleen
      that presented as a large solitary mass.

PMID- 18830110
TI  - Ovarian fibromatosis: magnetic resonance imaging findings with pathologic
      correlation.
AB  - Ovarian fibromatosis is a rare benign nonneoplastic condition with ovarian
      enlargement in young women and characterized by a proliferation of collagen
      producing spindle cells surrounding normal ovarian structures. We reported
      magnetic resonance findings of a case that the affected ovarian parenchyma with
      follicles was surrounded by very low intense thick fibrous tissue on T2-weighted
      images such as "black garland" around the ovary. The magnetic resonance findings
      well reflected the pathological feature of the disease and may be diagnostic.

PMID- 18830111
TI  - Multidetector computed tomography pulmonary angiography: does arm position affect
      pulmonary artery enhancement?
AB  - OBJECTIVE: To evaluate whether arm position affects pulmonary artery enhancement
      in computed tomographic pulmonary angiography (CTPA). METHODS: Study protocol had
      local ethics committee approval. Eighty-six patients who received 16 detector row
      CTPA for suspected pulmonary embolism were scanned with their contrast-injected
      arm resting at their side and compared with 94 patients who were scanned with
      both arms resting above their head. Two radiologists assessed pulmonary artery
      enhancement with a region-of-interest measurement of the main pulmonary artery
      density, scored the degree of beam-hardening artifact arising from the superior
      vena cava (SVC) and from the dependent arm that crossed the pulmonary arteries (1
      = no artifact, 5 = artery obscured), and measured the degree of central venous
      compression of the injected veins at the thoracic inlet. A 2-tailed t test was
      performed to compare pulmonary artery density and central venous compression.
      RESULTS: There was no difference in pulmonary artery enhancement between the 2
      arm positions. Mean density of contrast in the main pulmonary artery was 329
      Hounsfield units (HU) (95% confidence interval (CI), 310-350) in the arm-down
      group, compared with 325 HU (95% CI, 306-346) in the arm-up group (P = 0.65).
      Greater compression of the central veins occurred in the arm-up group (48.5%; 95%
      CI, 42.3%-54.8%) than in the arm-down group (22.3%; 95% CI, 16.8%-27.8%) (P <
      0.05). There was also more beam hardening arising from contrast in the SVC in the
      arm-up group (P < 0.0001). CONCLUSIONS: Arm position does not affect pulmonary
      arterial enhancement during CTPA. There was greater central venous compression
      and more beam-hardening artifact arising from the SVC when the arm was held above
      the head.

PMID- 18830112
TI  - The prevalence of symptomatic and coincidental pulmonary embolism on computed
      tomography.
AB  - PURPOSE: To investigate the proportion of pulmonary embolism (PE) on computed
      tomographic pulmonary angiography (CTPA) and the proportion of coincidental PE on
      regular contrast-enhanced CT in oncological and nononcological patients. METHODS:
      This study received internal review board approval and was Health Insurance
      Portability and Accountability Act compliant. All consecutive adult patients who
      had contrast-enhanced chest CT or dedicated CTPA during January 2005 were
      studied. Procedural codes were used to identify cases, and all CT images were
      reviewed. Clinical data collected included oncology status, chemotherapy regimen,
      site of tumor, and location of PE. chi2 Tests were used for statistical analysis.
      RESULTS: Two hundred twenty-nine patients had CTPA, and 27 (11.8%) of them were
      positive for PE. Of 1168 patients who had contrast-enhanced CT for other
      indications, coincidental PE was found in 21 patients (1.8%). The proportions of
      coincidental PE were 3.3% of patients with progressive cancer, 2.5% of patients
      with stable cancer, 0.7% of patients with no evidence of cancer posttreatment,
      and 1.0% of nononcological patients. Coincidental PE was found more frequently in
      patients with progressive cancer compared with nononcological patients (P =
      0.035). Patients who were on chemotherapy also had a higher risk of coincidental
      PE (P=0.019). CONCLUSIONS: The prevalence of symptomatic PE on dedicated CTPA was
      11.8%, and the rate of coincidental PE on contrast-enhanced CT was 1.8%.
      Coincidental PE was significantly higher inpatients with progressive cancer or
      those receiving chemotherapy.

PMID- 18830113
TI  - Computed tomography findings in patients with tracheal paracoccidioidomycosis.
AB  - OBJECTIVE: To evaluate the high-resolution computed tomographic (CT) findings of
      patients with tracheal paracoccidioidomycosis. METHODS: The high-resolution CT
      scans of 178 patients with pulmonary paracoccidioidomycosis were reviewed, and 4
      cases of proven tracheal involvement were studied. There were 3 male and 1 female
      patients, with ages ranging from 44 to 62 years (average, 49.2 years). The CT
      scans were retrospectively analyzed with special attention to the location of
      airway lesions, patterns of wall thickening, and occurrence of abnormal adjacent
      lymph nodes. Images were reviewed by 2 radiologists who reached decisions by
      consensus. RESULTS: The CT findings were circumferential parietal thickening (n =
      4) and irregular (n = 3) or smooth (n = 1), with submucosal nodules (n = 2).
      Enlarged mediastinal lymph nodes were seen in 1 patient. CONCLUSIONS: The CT
      findings in patients with tracheal paracoccidioidomycosis were circumferential
      irregular thickening of the tracheal wall, with submucosal nodules.

PMID- 18830114
TI  - Performance evaluation of 4 measuring methods of ground-glass opacities for
      predicting the 5-year relapse-free survival of patients with peripheral nonsmall
      cell lung cancer: a multicenter study.
AB  - OBJECTIVE: To evaluate the performance of 4 methods of measuring the extent of
      ground-glass opacities as a means of predicting the 5-year relapse-free survival
      of patients with peripheral nonsmall cell lung cancer (NSLC). METHODS: Ground
      glass opacities on thin-section computed tomographic images of 120 peripheral
      NSLCs were measured at 7 medical institutions by the length, area, modified
      length, and vanishing ratio (VR) methods. The performance (Az) of each method in
      predicting the 5-year relapse-free survival was evaluated using receiver
      operating characteristic analysis. RESULTS: The mean Az value obtained by the
      length, area, modified length, and VR methods in the receiver operating
      characteristic analyses was 0.683, 0.702, 0.728, and 0.784, respectively. The
      differences between the mean Az value obtained by the VR method and by the other
      3 methods were significant. CONCLUSIONS: Vanishing ratio method was the most
      accurate predictor of the 5-year relapse-free survival of patients with
      peripheral NSLC.

PMID- 18830115
TI  - Computed tomographic findings and prognosis in thymic epithelial tumor patients.
AB  - OBJECTIVE: To determine which computed tomographic findings are associated with
      high-risk thymic epithelial tumors and a poor prognosis. METHODS: Computed
      tomographic findings of thymic epithelial neoplasms were retrospectively
      evaluated in 75 patients diagnosed with thymic tumor between January 1997 and
      October 2003. We analyzed the correlation of the computed tomographic findings,
      histological subtype according to the World Health Organization classification,
      and the prognosis. RESULTS: There were 34 with type A approximately B1 tumor and
      41 with type B2 approximately C tumor. On multiple regression analysis, vascular
      obliteration and a blunt sternum-anterior mediastinum angle were more frequent
      with thymic carcinoma than with thymoma. On multivariate analysis, pleural
      effusion and mediastinal fat infiltration on initial computed tomography had a
      significant impact on survival. CONCLUSIONS: Vascular obliteration and a blunt
      sternum-anterior mediastinum angle were predictive of thymic carcinoma. Pleural
      effusion and mediastinal fat infiltration were predictive of a poor prognosis.

PMID- 18830116
TI  - Well-differentiated fetal adenocarcinoma of the lung: early-phase sequential high
      resolution computed tomographic findings.
AB  - Well-differentiated fetal adenocarcinoma is a rare primary adenocarcinoma
      originating in the lung. We present an early phase case that was followed up for
      2 years with chest roentgens and high-resolution computed tomography.
      Multicentric origin was suspected in the sequential high-resolution computed
      tomography study findings.

PMID- 18830117
TI  - The prevalence and significance of incidental thyroid nodules identified on
      computed tomography.
AB  - PURPOSE: The purpose of this study was to assess the prevalence of incidental
      thyroid nodules (ITN) found on computed tomography (CT) of the neck and to
      determine whether CT characteristics could distinguish malignant from benign
      thyroid lesions. MATERIALS AND METHODS: We retrospectively reviewed CT scans in
      734 patients without known thyroid disease (384 men and 350 women; mean age, 49.8
      +/- 13.7 years). The CT findings of ITN such as size, shape (anteroposterior
      transverse diameter ratio [AP/T ratio]), margin, peripheral enhancing rim,
      intralesional calcification, and attenuation characteristics were analyzed and
      correlated with ultrasonographic (US) findings. RESULTS: One hundred sixty ITNs
      were noted in 123 (16.8%) patients. Of 120 ITNs whose histological diagnoses were
      available, 15 (12.5%) were malignant. Malignant nodules more frequently showed
      nodular or rim calcifications (46.7% vs 13.3%; P < 0.0005), AP/T ratio of greater
      than 1.0 (33.3% vs 9.5%; P < 0.05), and mean attenuation value on contrast
      enhanced scan of greater than 130 Hounsfield units (86.7% vs 49.5%; P < 0.05)
      than benign nodules. CONCLUSIONS: We found at least a 9.4% (15/160) prevalence of
      malignancy among ITN detected on CT. The further evaluation with US or biopsy
      should be performed, if an ITN shows CT features suggesting malignancy
      (calcification; AP/T ratio, >1.0; or mean attenuation value, >130 HU).

PMID- 18830118
TI  - Rapid 3-dimensional imaging of embryonic craniofacial morphology using
      microscopic computed tomography.
AB  - OBJECTIVE: Microscopic computed tomography (microCT) has been recently applied to
      morphological evaluation of mouse embryos with or without congenital
      malformations, and 3-dimensional (3D) digital images of the whole embryo can be
      obtained. In the present study, the authors report a modified, rapid technique of
      3D embryonic microCT without processing with osmium tetroxide. METHODS: Normal
      embryonic days 10.5 to 11 mouse embryos, as well as those with craniofacial
      anomalies treated with teratogens, were examined. After fixation, we processed
      the embryo samples with hexamethyldisilazane, instead of highly toxic osmium
      tetroxide in the original method. RESULTS: Our protocol enabled clear 3D
      craniofacial imaging of the normal and anomalous mouse embryos within a short
      period of 20 minutes or 1 hour. In addition, some anatomical landmarks were
      clearly detected in the reconstituted craniofacial section images. CONCLUSION:
      Our present data suggest a possible role of microCT for high-throughput
      morphological screening of the mouse embryos with craniofacial anomalies.

PMID- 18830119
TI  - Silent white matter lesion in linear scleroderma en coup de sabre.
AB  - We report a patient with linear scleroderma en coup de sabre without neurological
      symptoms despite the presence of large white matter lesions. The patient
      underwent 3.0-T magnetic resonance (MR) examinations including diffusion tensor
      imaging, time-resolved contrast-enhanced MR angiography, susceptibility-weighted
      imaging, and proton MR spectroscopy. These imaging findings suggested increased
      vascular permeability and microbleeding without abnormalities of metabolites. Our
      observation is consistent with vasculopathy and may be helpful in the proper
      diagnosis and treatment of linear scleroderma en coup de sabre.

PMID- 18830120
TI  - Craniofacial melorheostosis.
AB  - Melorheostosis is a rare benign disease of cortical bone most frequently
      presenting as peripheral hyperostosis with a characteristic "melting wax"
      appearance on conventional radiographs. The disease most frequently affects the
      appendicular skeleton and is seen only rarely in the craniofacial bones. We
      discuss a case of melorheostosis in the nasal cavity and skull base with an
      atypical radiographic appearance and suggest findings that may differentiate
      craniofacial melorheostosis from more common entities in this region.

PMID- 18830121
TI  - Rhabdomyosarcomatous differentiation in gastrointestinal stromal tumors after
      tyrosine kinase inhibitor therapy: a novel form of tumor progression.
AB  - Approximately 80% of advanced metastatic gastrointestinal stromal tumors (GISTs)
      respond to treatment with the tyrosine kinase inhibitor (TKI) imatinib mesylate.
      However, the majority of patients suffer disease progression at a median of 2
      years due to drug resistance. In general, progressing GISTs retain their typical
      morphology. Herein, we report 5 cases of progressing metastatic GIST with
      heterologous rhabdomyoblastic differentiation after TKI treatment. Histologic,
      immunohistochemical, and mutational analyses were performed on histologically
      classic GISTs and components with rhabdomyoblastic differentiation. There were 3
      men and 2 women (ranging from 35 to 66 y of age). Three tumors were localized at
      presentation (2 stomach and 1 small bowel) and 2 presented with metastases. All
      localized primary tumors were high risk. Two tumors showed spindle cell
      morphology and 3 were epithelioid, including 1 with marked pleomorphism. After
      resection of the 3 localized primary tumors, intra-abdominal (2 patients) and
      liver (1 patient) metastases developed. All patients were treated with imatinib
      and showed partial clinical responses (4 patient) or stable disease (1 patient).
      Four patients subsequently progressed; 2 patients were treated with sunitinib
      after progression with minor responses. Four patients underwent surgical
      debulking. At last follow-up (range: 20 to 87 mo), 2 patients died of disease, 2
      were alive with metastatic disease resistant to TKIs, and 1 was alive without
      evidence of disease. In all cases, rhabdomyoblastic differentiation was
      identified adjacent to areas with classic GIST morphology in at least 1
      metastatic site; in 1 case, the primary tumor (after treatment with TKIs) showed
      heterologous differentiation. The rhabdomyoblastic components showed strong and
      diffuse positivity for desmin and expressed myogenin, whereas KIT was negative in
      the rhabdomyoblastic component in all cases. Primary KIT mutations were detected
      in both the conventional GIST and rhabdomyoblastic components from all patients:
      KIT exon 11 mutations in 4 cases and a platelet-derived growth factor receptor
      alpha gene exon 18 deletion in 1 case. No secondary mutations of the type
      associated with TKI resistance were identified in the rhabdomyoblastic areas.
      This is the first report of rhabdomyoblastic differentiation occurring in GISTs
      that progressed on TKI therapy. It is associated with loss of KIT expression, but
      retention of the receptor tyrosine kinase mutation of the precursor GIST. The
      rhabdomyoblastic differentiation can represent a diagnostic pitfall. The
      molecular mechanisms for this form of TKI-resistant clonal evolution remain to be
      determined.

PMID- 18830123
TI  - Pyloric gland adenoma: an entity distinct from gastric foveolar type adenoma.
AB  - Pyloric gland adenoma (PGA) is a rare neoplasm demonstrating gastric epithelial
      differentiation. In this series, we studied 41 PGAs from 36 patients. We compared
      them to 28 gastric foveolar type gastric adenomas (GTAs) from 25 patients. PGAs
      occurred in an older population with a mean age of 73 compared with 48 in GTAs
      (P<0.001). There was a significant female predominance, particularly for gastric
      PGAs. Morphologically, PGAs were characterized by closely packed pyloric gland
      type tubules with a monolayer of cuboidal to low columnar epithelial cells
      containing round nuclei and pale to eosinophilic cytoplasm with a ground glass
      appearance. The cells lacked an apical mucin cap, a feature distinct from GTAs.
      An immunohistochemical panel of mucin core peptides (MUCs) and CDX2 was performed
      on a subset of the lesions. All PGAs expressed MUC6 with coexpression of MUC5AC,
      whereas GTAs expressed predominantly MUC5AC without MUC6. Both lesions lacked
      CDX2 and MUC2 except in areas of intestinal metaplasia (IM) found in some PGAs.
      Histologic features consistent with conventional dysplasia were found in 26
      (63.4%) PGAs. Using a 2-tier grading system, 5 (12.2%) cases demonstrated low
      grade dysplasia whereas 21 (51.2%) cases showed high-grade dysplasia including 5
      (12.2%) cases with an associated intramucosal or more deeply invasive
      adenocarcinoma. This was significantly different from GTAs; all cases showed only
      low-grade dysplasia (P<0.001). In addition, 60% of gastric PGAs were associated
      with IM in the surrounding mucosa and 40% of lesions arose in a background of
      autoimmune gastritis, whereas these 2 conditions were only associated with 1 case
      (3%) of GTA. In summary, PGA is a distinct entity. Despite its bland histologic
      appearance, it is much more likely to be accompanied by background IM and
      autoimmune gastritis and can evolve into invasive adenocarcinoma displaying
      pyloric gland differentiation.

PMID- 18830122
TI  - Pathologic predictors of microsatellite instability in colorectal cancer.
AB  - Identification of microsatellite unstable (MSI-H) colorectal cancers (CRCs) is
      important not only for the identification of hereditary nonpolyposis colorectal
      cancer syndrome but also because MSI-H CRCs have a better prognosis and may
      respond differently to 5-fluorouracil-based chemotherapy. We present 2 nearly
      equivalent logistic regression models for clinical use that predict
      microsatellite instability based on the review of 1649 CRCs from patients of all
      ages collected in a population-based case control study in northern Israel. One
      hundred ninety-eight of these 1649 tumors demonstrated a high degree of
      microsatellite instability (12%). Multivariate analysis found that >2 tumor
      infiltrating lymphocyte (TIL) cells per high-powered field, the lack of dirty
      necrosis, the presence of a Crohn-like reaction, right-sided location, any
      mucinous differentiation (mucinous or focally mucinous) and well or poor
      differentiation, and age less than 50 were all independent predictors of MSI-H.
      We developed 2 logistic regression models that differ only by the statistical
      approach used to analyze the number of TIL cells per high-powered field, where
      the slightly more accurate (and complex) model uses the log of the total number
      of TIL cells. The simpler clinical model uses a cut-off of 2>TIL cells per high
      powered field. The accuracy of both models is high, with an 85.4% versus 85.0%
      probability of correctly classifying tumors as MSI-H. By employing the simpler
      model, pathologists can predict the likelihood of microsatellite instability by
      compiling the MSI probability score (Table 4 and Fig. 1) from simple histologic
      and clinical data available during sign-out. Our model shows that approximately
      43% of CRCs have a MSI probability score of 1 or less and hence have little
      likelihood (<3%) of being MSI-H. Although this model is not perfect in predicting
      microsatellite instability, its use could improve the efficiency of expensive
      diagnostic testing.

PMID- 18830124
TI  - Transitional cell metaplasia of fallopian tube fimbriae: a potential mimic of
      early tubal carcinoma in risk reduction salpingo-oophorectomies from women With
      BRCA mutations.
AB  - Germline mutations in the hereditary breast/ovary carcinoma genes BRCA1 or BRCA2
      confer increased lifetime risk for ovarian, fallopian tube, and primary
      peritoneal carcinoma. This risk can be minimized by prophylactic surgery. Risk
      reducing salpingo-oophorectomy (RRSO) provides 2 potential benefits: long-term
      cancer risk reduction and immediate detection of occult early carcinoma, which
      frequently arises in the tubal fimbriae. Recognition of occult early tubal
      carcinoma is challenging because it is often microscopic in size and can be
      confined to the fimbrial epithelium without invasion. Transitional cell
      metaplasia is a benign epithelial alteration that is a common finding in the
      serosa of the tube but is underrecognized in the tubal fimbriae, where it may
      mimic tubal intraepithelial carcinoma. The aim of this study was to define the
      incidence, morphology, immunophenotype, and distribution of transitional cell
      metaplasia of the fimbriae in RRSO specimens from 96 women with BRCA germline
      mutations and to compare these features to those of tubal intraepithelial
      carcinoma in this cohort. RRSO specimens from an additional 30 women at increased
      risk for ovarian cancer based on strong family history were also studied, along
      with RRSO from 1 patient with Lynch syndrome, and 1 patient with PTEN mutation.
      Transitional cell metaplasia of the fimbriae was present in 26% of all RRSO
      specimens. It was commonly multifocal (67%), with involvement of the tip, edges,
      or base of the fimbrial plicae. Average size of a metaplastic focus was 1.3 mm
      (range: 0.1 to 10 mm). None of the metaplastic foci expressed p53 by
      immunohistochemistry nor was there increased staining for the proliferation
      marker MIB-1. Occult early carcinoma was detected in 6/128 RRSO specimens. Median
      tumor size was 2.7 mm (range: 1 to 11 mm). All expressed p53 and showed markedly
      increased MIB-1 staining. The key criteria distinguishing transitional cell
      metaplasia from tubal intraepithelial carcinoma were uniform cell size and shape,
      normal nucleus:cytoplasm ratios, lack of nuclear atypia, presence of nuclear
      grooves, lack of mitoses, and absence of p53 expression or increased staining for
      MIB-1. No particular clinical variables (BRCA 1 vs. BRCA 2 mutation, parity,
      personal history of breast cancer, prior abdomino-pelvic surgery, or
      intraoperative findings) or benign pathologic alterations in the RRSO specimens
      were associated with the presence of transitional cell metaplasia of the
      fimbriae. None of the patients with this finding developed peritoneal carcinoma
      during follow-up ranging from 1 month to 9 years. This study demonstrates that
      transitional cell metaplasia of the fimbriae is a common benign finding in RRSO
      specimens that should not be confused with the much less common finding of tubal
      intraepithelial carcinoma.

PMID- 18830125
TI  - Follicular lymphoma of the thyroid gland.
AB  - The majority of lymphomas arising in the thyroid gland are mucosa-associated
      lymphoid tissue lymphomas and diffuse large B-cell lymphomas, which arise from a
      background of chronic lymphocytic thyroiditis. Follicular lymphoma may also
      present in the thyroid gland, but its clinicopathologic features at this site are
      not well characterized, leading to difficulties in diagnosis and clinical
      management. We have addressed this problem by studying the clinical, morphologic,
      immunophenotypic, and genetic features of 22 such cases. All cases showed
      morphology characteristic of follicular lymphoma, however, in many the
      interfollicular neoplastic infiltrate was particularly prominent and all
      lymphomas contained readily identifiable and often striking lymphoepithelial
      lesions, features heretofore considered indicative of mucosa-associated lymphoid
      tissue lymphoma at this site. Furthermore, 13 of 18 cases for which sufficient
      evidence was available had clinical and/or histologic evidence of chronic
      lymphocytic thyroiditis. Analysis of genetic and immunohistochemical features
      identified 2 distinct groups. In 1 group, similar to typical adult follicular
      lymphoma, cases carried a t(14;18)/IGH-BCL2 and/or expressed Bcl-2, and were
      mostly CD10-positive and of World Health Organization (WHO) grade 1 to 2.
      Follicular lymphomas in the other group lacked IGH-BCL2 and Bcl-2 expression,
      were often of WHO grade 3 and were often CD10-negative, similar to the minority
      of follicular lymphomas previously described that are Bcl-2-negative and are
      often encountered at other extranodal sites. The 2 groups differed in clinical
      stage at presentation, 11 patients in the former group but none in the latter
      group having disease beyond the thyroid gland. Appreciation of the spectrum of
      morphologic, immunophenotypic, and genetic characteristics of follicular lymphoma
      presenting in the thyroid gland should aid both diagnosis and clinical
      management.

PMID- 18830126
TI  - Prevalence of germline mutations in the TTR gene in a consecutive series of
      surgical pathology specimens with ATTR amyloid.
AB  - Transthyretin-derived amyloidosis (ATTR) amyloidosis is the third most prevalent
      amyloid type in surgical pathology and may occur as a hereditary disease with
      germline mutations in the TTR gene or as senile systemic amyloidosis (SSA)
      without mutations. Distinction between hereditary ATTR amyloidosis and SSA is of
      central importance, as the former necessitates genetic counseling and can be
      treated by liver transplantation. However, little is known about the prevalence
      of hereditary ATTR amyloidosis in surgical pathology specimens. We have examined
      the distribution of hereditary ATTR amyloidosis and SSA in a consecutive series
      of surgical pathology specimens with histologically and immunohistochemically
      confirmed ATTR amyloid. Thirty-three consecutive patients were retrieved from the
      Amyloid Registry of the Charite University Hospital. Genomic DNA was extracted
      from formalin-fixed and paraffin-embedded tissue or patient blood and examined by
      DNA sequencing. ATTR amyloid was found in the gastrointestinal tract,
      endomyocardium, peripheral nerve, carpal tunnel ligament, synovia, breast, and
      testicle. Amyloid fibrils were present as interstitial and vascular deposits, as
      evidenced by Congo red staining. TTR gene mutations were detected in 12 of 30
      patients, with p.Val30Met being the most prevalent (5 patients). Furthermore, 2
      novel mutations (p.Asp39Val and p.Glu54Asp) were found. In patients carrying a
      mutation, ATTR amyloid was found in the gastrointestinal tract, myocardium,
      nerve, and testicles. To conclude, the hereditary form of ATTR amyloid seems to
      be more common in elderly patients than previously thought. It is, therefore,
      important to genetically test every patient when diagnosing ATTR amyloidosis.

PMID- 18830127
TI  - A limited panel of immunomarkers can reliably distinguish between clear cell and
      high-grade serous carcinoma of the ovary.
AB  - The distinction of ovarian clear cell carcinomas (CCCs) from high-grade serous
      carcinomas (HG-SCs) is sometimes a diagnostic challenge. With the recognition
      that CCCs respond poorly to conventional chemotherapy there are efforts to
      initiate clinical trials for CCC, making accurate diagnosis critical. The purpose
      of this study was to test and validate a set of antibodies that could aid in the
      diagnosis of CCC, using a series of cases from different centers in North
      America. Using a test set of 133 CCCs, we identified the following markers:
      Cyclin E, estrogen receptor, hepatocyte nuclear factor (HNF)-1beta, Ki-67, p21,
      p53, and Wilms tumor (WT)1 that show significant discrimination from 200 HG-SCs.
      For validation, these markers were characterized on an independent set of 104
      CCCs from 3 other centers. There were no significant differences in expression of
      these 7 markers between the independent test and validation sets of CCC.
      Combining all CCC cases (N=237), HNF-1beta showed the highest sensitivity (82.5%)
      and specificity (95.2%) for CCC, and WT1 for HG-SC (sensitivity: 79.9%,
      specificity: 97.4%). A diagnostic panel consisting of WT1, ER, and HNF-1beta
      demonstrated nearly identical performance as a panel using all 7 markers in
      distinguishing CCCs from HG-SCs, correctly classifying 84% of cases. Three
      percent of cases were misclassified and 13% carried an uninformative triple
      negative immunophenotype. CCCs show a distinct, reproducible immunophenotype,
      compared with HG-SCs, and a panel of 3 immunomarkers can serve as a diagnostic
      aid in problematic cases.

PMID- 18830128
TI  - Infantile digital fibroma/fibromatosis: a clinicopathologic and
      immunohistochemical study of 69 tumors from 57 patients with long-term follow-up.
AB  - The clinicopathologic and immunohistochemical features of 69 pediatric examples
      of infantile digital fibroma/fibromatosis (IDF) were analyzed. Thirty males, 26
      females, and 1 child (sex unstated) ranging from newborn to 120 months of age
      (median, 12 mo) manifested 74 lesions (5 identified in follow-up) involving the
      toe or finger (n=71) and the hand or foot (n=3). Tumors ranged in size from 3 to
      35 (median, 10) mm. All but 4 study members presented with a solitary lesion.
      Metachronous IDFs developed in 7 patients within 17 to 82 months.
      Microscopically, a cytologically bland, fibroproliferative lesion was observed
      forming a dome-shaped/polypoid nodule directly beneath the epidermis and invading
      dermal adnexa. Mitotic figures per 20 high-powered fields ranged from 0 to 7
      (median, 1). Paranuclear cytoplasmic inclusions were identified in 57 tumors.
      Tumor cells immunohistochemically expressed calponin (11 of 11 tumors), desmin
      (9/9), alpha-smooth muscle actin (11/11), CD99 (11/11), CD117 (6/8), heavy
      caldesmon (2/11 and scattered cytoplasmic inclusions in 4 tumors), CD10 (1/9),
      nuclear beta-catenin (2/11), and CD34 (1/11), but not muscle actin (HUC1-1),
      keratins, estrogen/progesterone receptor proteins, or activated caspase-3. Twenty
      eight of 38 patients (74%) experienced recurrent/persistent disease (single in
      22; multiple in 6) (median, 4 mo after surgery). One recurrent tumor
      spontaneously regressed and the size of another remained unchanged for almost 17
      years before reexcision. All 23 patients with >5 years follow-up are currently
      disease free (median disease-free interval, 23 y). Minor postoperative
      functional/cosmetic complaints were reported in 47%. No patient with adequate
      clinical data developed the digitocutaneous dysplasia syndrome or a conventional
      fibromatosis, or relayed a family history of IDF/conventional fibromatosis. Our
      results indicate that IDF is a unique myofibroblastic process separable from
      conventional fibromatoses and from histologic mimics. Conservative excision or
      observation after biopsy (with additional surgery employed as necessary) are
      recommended treatment options.

PMID- 18830129
TI  - Coenzyme Q0 induces apoptosis and modulates the cell cycle in estrogen receptor
      negative breast cancer cells.
AB  - We postulated that methoxy-substituted cyclic compounds could inhibit estrogen
      receptor (ER) negative breast cancer growth in vitro. Therefore, this study
      assessed the cytotoxic potential of various methoxy-substituted cyclic compounds
      [7,8-dimethoxyflavone, 4-methoxyphenylacetic acid, 2-methoxyphenylacetic acid, 4
      methoxybenzophenone, 5-methoxy-1-indanone, and coenzyme Q0 (CoQ0)] toward ER
      negative human breast cancer cells (MDA-MB-231 and SKBr3). Cytotoxicity was
      assessed using the sulforhodamine B assay. CoQ0 demonstrated the strongest
      cytotoxicity toward MDA-MB-231 and SKBr3 cells with IC50 values of 1.7 micromol/l
      and 3.1 micromol/l, respectively, whereas the other compounds were either much
      less potent or completely lacked cytotoxicity toward both breast cancer cell
      lines. Therefore, only CoQ0 was examined for its ability to modulate cell cycle
      progression and induce apoptosis. Cell cycle experiments, using propidium iodide
      staining and flow cytometry, demonstrated that CoQ0 at 7.5 micromol/l increased
      the proportion of MDA-MB-231 cells in G1/G0-phase by 16.6+/-0.6% of control
      (P<0.05), and increased in the proportion of S-phase SKBr3 cells by 37.8+/-5.8%
      over control (P<0.05). Induction of apoptosis was determined using propidium
      iodide/Annexin-V-FLUOS staining followed by flow cytometry. The results
      demonstrated that treatment with CoQ0 (7.5 micromol/l) increased the proportion
      of apoptotic MDA-MB-231 and SKBr3 cells by 12-fold and 4-fold over control
      (P<0.05), respectively. Thus, CoQ0 is a potent cytotoxic drug that induces
      apoptosis and modulates cell cycle progression in ER-negative breast cancer
      cells. Therefore, CoQ0 is an appropriate candidate for further study and
      development as a potential drug for ER-negative breast cancer.

PMID- 18830130
TI  - Genetic relationship between anxiety-related and fear-related behaviors in BXD
      recombinant inbred mice.
AB  - Mood and anxiety disorders, and rodent phenotypic measures modeling these
      disorders, have a strong genetic component. Various assays are used to study the
      neurobiological basis of fear-related and anxiety-related behaviors, phenotype
      genetically modified mice, and elucidate pharmacological modulation of these
      behaviors for medication development. Earlier work, however, suggests that
      different trait measures are mediated by partly overlapping but ultimately
      distinct genetic factors. In this study, we assessed a novel panel of 23
      C57BL/6JxDBA/2J (BXD) recombinant inbred strains on various trait measures of
      Pavlovian fear conditioning and anxiety-like behavior (novel open field, elevated
      plus-maze), as well as sensory (acoustic startle, prepulse inhibition of startle)
      and motor (baseline coordination and learning on accelerating rotarod) function.
      Results showed that traits were continuously distributed across strains and had
      modest to strong R values. Principal components analysis resolved the data into
      five factors: factor 1 loaded fear-related traits, factor 2 loaded elevated plus
      maze measures as well as context fear, factor 3 loaded novel open field measures
      and plus-maze closed arm entries, factor 4 loaded rotarod motor function, and
      factor 5 loaded acoustic startle and prepulse inhibition. These data add to
      evidence that murine measures of fear-like and anxiety-like traits reflect
      distinct constructs mediated by dissociable gene variants.

PMID- 18830131
TI  - Alcohol-related cancers and genetic susceptibility in Europe: the ARCAGE project:
      study samples and data collection.
AB  - Cancers of the upper aerodigestive tract (UADT) include those of the oral cavity,
      pharynx (other than nasopharynx), larynx, and esophagus. Tobacco smoking and
      consumption of alcoholic beverages are established causes of UADT cancers,
      whereas reduced intake of vegetables and fruits are likely causes. The role of
      genetic predisposition and possible interactions of genetic with exogenous
      factors, however, have not been adequately studied. Moreover, the role of pattern
      of smoking and drinking, as well as the exact nature of the implicated dietary
      variables, has not been clarified. To address these issues, the International
      Agency for Research on Cancer initiated in 2002 the alcohol-related cancers and
      genetic susceptibility (ARCAGE) in Europe project, with the participation of 15
      centers in 11 European countries. Information and biological data from a total of
      2304 cases and 2227 controls have been collected and will be used in a series of
      analyses. A total of 166 single nucleotide polymorphisms of 76 genes are being
      studied for genetic associations with UADT cancers. We report here the
      methodology of the ARCAGE project, main demographic and lifestyle characteristics
      of the cases and controls, as well as the distribution of cases by histology and
      subsite. About 80% of cases were males and fewer than 20% of all cases occurred
      before the age of 50 years. Overall, the most common subsite was larynx, followed
      by oral cavity, oropharynx, esophagus and hypopharynx. Close to 90% of UADT
      cancers were squamous cell carcinomas. A clear preponderance of smokers and
      alcohol drinkers among UADT cases compared with controls was observed.

PMID- 18830132
TI  - Chemoablation of metastatic melanoma using intralesional Rose Bengal.
AB  - To study the effects of intralesional Rose Bengal for chemoablation of metastatic
      melanoma. Twenty-six target lesions in 11 patients with locoregionally recurrent
      disease were injected with the agent PV-10 (10% w/v Rose Bengal in saline) at a
      dose of 0.5 ml/cc lesion volume. An additional 28 untreated lesions were observed
      for potential bystander effect. The treatment was well tolerated and an objective
      response was observed in 12 target lesions, with an additional seven lesions
      remaining static over at least 12 weeks of observation. In this dose-evaluation
      study, response rate was dose dependent, increasing to 69% after higher dose
      injections. Nontarget lesions exhibited a 27% objective response rate that
      increased to 44% in patients exhibiting a positive response of target lesions.
      These findings indicate that intralesional Rose Bengal is nontoxic and could
      benefit patients with metastatic melanoma.

PMID- 18830133
TI  - Frequency of mitochondrial 12S ribosomal RNA variants in an adult cystic fibrosis
      population.
AB  - In adult cystic fibrosis patient populations, gram-negative bacteria,
      particularly Pseudomonas aeruginosa, frequently require aggressive therapy
      including systemic antibiotics, bronchodilators and airway clearance techniques.
      Aminoglycosides including tobramycin are used frequently to control these chronic
      airway infections. They, however, cause important nephrotoxic and ototoxic
      effects that can significantly alter the quality of life. We investigated the
      genetic predisposition to aminoglycoside ototoxicity in a typical unscreened
      North American cystic fibrosis population by screening for variants in
      mitochondrial 12S ribosomal RNA and noted several polymorphisms occurred at
      higher frequencies than expected and were associated with clinically significant
      cases of hearing loss. In the population studied, both patients possessing the
      1555A>G transition exhibited profound ototoxicity after nontoxic dosing of
      tobramycin. We also identified new homoplasmic genetic variations in the
      mitochondrial 12S ribosomal RNA, several of which occurred in highly conserved
      regions of the gene and were present in patients with moderate-to-severe
      ototoxicity after exposure to aminoglycosides.

PMID- 18830134
TI  - Chromosome 9: linkage for borderline personality disorder features.
AB  - OBJECTIVE: A large-scale twin study implicated genetic influences on borderline
      personality disorder (BPD) features, with a heritability estimate of 42%. To
      date, no genome-wide linkage study has been conducted to identify the genomic
      region(s) containing the quantitative trait loci that influence the manifestation
      of BPD features. METHODS: We conducted a family-based linkage study using Merlin
      regress. The participating families were drawn from the community-based
      Netherlands Twin Register. The sample consisted of 711 sibling pairs with
      phenotype and genotype data, and 561 additional parents with genotype data. BPD
      features were assessed on a quantitative scale. RESULTS: Evidence for linkage was
      found on chromosomes 1, 4, 9, and 18. The highest linkage peak was found on
      chromosome 9p at marker D9S286 with a logarithm of odds score of 3.548 (empirical
      P=0.0001). CONCLUSION: To our knowledge, this is the first linkage study on BPD
      features and shows that chromosome 9 is the richest candidate for genes
      influencing BPD. The results of this study will move the field closer to
      determining the genetic etiology of BPD and may have important implications for
      treatment programs in the future. Association studies in this region are,
      however, warranted to detect the actual genes.

PMID- 18830135
TI  - Prevalence of syphilis and human immunodeficiency virus infections among men who
      have sex with men in Shenzhen, China: 2005 to 2007.

PMID- 18830136
TI  - Sexual network structure among a household sample of urban african american
      adolescents in an endemic sexually transmitted infection setting.
AB  - BACKGROUND: Sexual networks play an important role in the transmission of
      sexually transmitted infections (STIs) and HIV. However, because of the
      challenges of collecting network data, relatively few empirical reports exist
      about the structure of sexual networks in general population samples. This study
      describes the structure of the sexual networks of a household sample of urban
      black adolescents living in an area with moderate endemic STI rates. METHODS:
      Random digit dialing was used to recruit a household sample of black adolescents
      from the Bayview-Hunter's Point neighborhood of San Francisco. Participants'
      recent partners and partners of partners were recruited through snowball
      sampling. Biologic samples were tested for current infection with gonorrhea or
      chlamydia. Social network analysis methods were used to describe the
      characteristics of the resulting sexual networks. RESULTS: One hundred and sixty
      six sexually active participants were connected to 388 network members in 159
      separate sexual network components. Despite relatively high prevalence of
      bacterial STIs (13%), components were small (3.5 people on average, and half
      involved only 2 people), linear and acyclic. Females were less central in their
      networks than males by local measures but just as central when overall structure
      was taken into account. CONCLUSIONS: Our results confirm, in a new setting,
      previous observations that sexual network structures necessary for endemic
      transmission of gonorrhea and chlamydia are sparsely connected.

PMID- 18830137
TI  - The program cost and cost-effectiveness of screening men for Chlamydia to prevent
      pelvic inflammatory disease in women.
AB  - BACKGROUND: Because men transmit Chlamydia trachomatis to women, screening men to
      prevent pelvic inflammatory disease in women may be a viable strategy. However,
      the cost-effectiveness of this approach requires careful assessment. METHODS:
      Data from a demonstration project and longitudinal study that examined screening
      men for chlamydia were applied to a compartment-based transmission model to
      estimate the cost-effectiveness of screening men for chlamydia compared with
      alternative interventions, including expanded screening of women and combining
      disease investigation specialist-provided partner notification with screening.
      Cases of pelvic inflammatory disease and quality-adjusted life years lost were
      the primary outcome measures. A male screening program that screened 1% of men in
      the population annually was modeled. RESULTS: A program targeting high-risk men
      for screening (those with a larger number of partners in the previous year than
      the general population and a higher chlamydia prevalence) was cost saving
      compared with using equivalent program dollars to expand screening of lower-risk
      women. Combining partner notification with male screening was more effective than
      screening men alone. In sensitivity analyses, the male program was not always
      cost saving but averaged $10,520 per quality-adjusted life year saved over
      expanded screening of women. CONCLUSIONS: Screening men can be a cost-effective
      alternative to screening women, but the men screened must have a relatively high
      prevalence compared with the women to whom screening would be expanded (under
      baseline assumptions, the prevalence in screened men was 86% higher than that of
      screened women). These modeling results suggest that programs targeting venues
      that have access to high-risk men can be effective tools in chlamydia prevention.

PMID- 18830138
TI  - Human papillomavirus vaccine acceptability among young adult men.
AB  - BACKGROUND: For human papillomavirus (HPV) vaccination to have maximum benefit to
      public health, both men and women should be vaccinated. Although efficacy trials
      in men are still ongoing, the HPV vaccine will likely be licensed for men in the
      near future. Little is known about men's interest in HPV vaccination. This study
      assessed whether informing men about the benefits of male HPV vaccination for
      their female sexual partner(s) boosted interest in the HPV vaccine beyond
      informing them about the benefits to men alone. Predictors of HPV vaccine
      acceptability were also identified. METHODS: Heterosexual male college students
      (n = 356) were randomly assigned to receive a self-protection versus a self
      protection and partner protection message about HPV and the quadrivalent HPV
      vaccine. Participants provided demographic and sexual history information, HPV
      related awareness and knowledge, health beliefs, and HPV vaccination intentions.
      RESULTS: : Men reported moderate interest in the HPV vaccine; vaccine
      acceptability did not differ by experimental condition. A multivariate regression
      model identified several independent predictors of HPV vaccine acceptability
      including sexual activity, perceived susceptibility to HPV, perceived benefits of
      the vaccine, perceived hassle and cost of vaccination, self-efficacy for
      vaccination, and perceived norms for vaccination. CONCLUSION: Informing men about
      the benefits of male HPV vaccination for reducing cervical cancer risk in women
      did not increase men's interest in the vaccine. Correlates of vaccine
      acceptability among men were generally consistent with those identified for
      women. Findings have important implications for future HPV vaccination campaigns
      targeting young adult men.

PMID- 18830139
TI  - Synthesis, IR spectra, crystal structure and DFT studies on 1-acetyl-3-(4
      chlorophenyl)-5-(4-methylphenyl)-2-pyrazoline.
AB  - 1-Acetyl-3-(4-chlorophenyl)-5-(4-methylphenyl)-2-pyrazoline has been synthesized
      and characterized by elemental analysis, IR and X-ray single crystal diffraction.
      Density functional (DFT) calculations have been carried out for the title
      compound by using the B3LYP method at the 6-311G** basis set level. The
      calculated results show that the predicted geometry can reproduce well the
      structural parameters. Predicted vibrational frequencies have been assigned and
      compared with experimental IR spectra and they are supported each other. On the
      basis of vibrational analyses, the thermodynamic properties of the title compound
      at different temperatures have been calculated, revealing the correlations
      between C(0)(p, m), S(0)(m), H(0)(m) and temperatures.

PMID- 18830140
TI  - New secoiridoid glycosides from the roots of Picrorhiza scrophulariiflora.
AB  - Three new secoiridoid glycosides, named picrogentiosides A (1), B (2) and C (3),
      have been isolated from the underground parts of Picrorhiza Scrophulariiflora,
      together with the two known compounds plantamajoside (4) and plantainoside D (5).
      Their structures were established by spectroscopic analyses and comparisons with
      data from related compounds. A pilot pharmacological study showed that
      picrogentiosides A (1) and B (2) have an immunomodulatory effect in vitro.

PMID- 18830141
TI  - Chemical composition, antioxidant and antibacterial properties of Achillea
      collina Becker ex Heimerl s.l. and A. pannonica Scheele essential oils.
AB  - The in vitro antioxidant and antimicrobial activities of two Achillea millefolium
      (Adanson) Koch s.l species essential oils (A. collina Becker ex Heimerl s.l. and
      A. pannonica Scheele, Asteraceae) originating from the Golija and Radan mountains
      (Serbia) were investigated. The chemical profiles of the essential oils were
      evaluated by GC-MS. Antioxidant activity was assessed as free radical scavenging
      capacity (RSC) towards 2,2-diphenyl-1-picrylhydrazil (DPPH) radicals, together
      with effects on lipid peroxidation (LP). Antibacterial activity was examined on
      21 bacterial strains. Based on the chemical composition of the essential oil, A.
      collina s.l. from Mount Golija was classified as a chamazulene chemotype
      (tetraploid). The high percentage of oxygenated monoterpenes and absence of
      azulene in the essential oil obtained from A. pannonica from Radan pointing that
      this population is octaploid. Essential oil of A. pannonica expressed stronger
      antimicrobial activity on almost all tested bacteria. Furthermore, this essential
      oil expressed higher scavenging effects on DPPH radical (IC(50) = 0.52 comparing
      to 0.62 mug/mL). Only in the LP evaluation, essential oil of A. collina s.l. from
      Golija exhibited stronger antioxidant activity (IC(50) = 0.75 comparing to 2.12
      mug/mL).

PMID- 18830143
TI  - Microwave synthesis of quaternary ammonium salts.
AB  - The microwave synthesis of several quaternary ammonium salts is described. The
      synthesis provides comparable or better yields than published methods with
      reduced reaction times and in the absence of solvent.

PMID- 18830142
TI  - Marine derived polysaccharides for biomedical applications: chemical modification
      approaches.
AB  - Polysaccharide-based biomaterials are an emerging class in several biomedical
      fields such as tissue regeneration, particularly for cartilage, drug delivery
      devices and gelentrapment systems for the immobilization of cells. Important
      properties of the polysaccharides include controllable biological activity,
      biodegradability, and their ability to form hydrogels. Most of the
      polysaccharides used derive from natural sources; particularly, alginate and
      chitin, two polysaccharides which have an extensive history of use in medicine,
      pharmacy and basic sciences, and can be easily extracted from marine plants
      (algae kelp) and crab shells, respectively. The recent rediscovery of poly
      saccharidebased materials is also attributable to new synthetic routes for their
      chemical modification, with the aim of promoting new biological activities and/or
      to modify the final properties of the biomaterials for specific purposes. These
      synthetic strategies also involve the combination of polysaccharides with other
      polymers. A review of the more recent research in the field of chemical
      modification of alginate, chitin and its derivative chitosan is presented.
      Moreover, we report as case studies the results of our recent work concerning
      various different approaches and applications of polysaccharide-based
      biomaterials, such as the realization of novel composites based on calcium
      sulphate blended with alginate and with a chemically modified chitosan, the
      synthesis of novel alginate-poly(ethylene glycol) copolymers and the development
      of a family of materials based on alginate and acrylic polymers of potential
      interest as drug delivery systems.

PMID- 18830144
TI  - Chemical composition, antifungal and antitumor properties of ether extracts of
      Scapania verrucosa Heeg. and its endophytic fungus Chaetomium fusiforme.
AB  - An endophytic fungus Chaetomium fusiforme was obtained from a liverwort, Scapania
      verrucosa. A comparison of the constituents of the ether extracts between S.
      verrucosa and the C. fusiforme culture was investigated by gas chromatography
      mass spectrometry (GC/MS). The yield of ether extract based on dried plant
      material was 0.6% and 59 compounds were found in S. verrucosa. (+)-Aromadendrene
      (9.12%), hexadecanoic acid (6.92%), 6-isopropenyl-4,8a-dimethyl-1,2,3,5,6,7,8,8a
      octahydro-naphthalen-2-ol (5.97%), s-tetrachloroethane (5.61%) and acetic acid
      (5.30%) were found to be the most abundant components among the 49 characterized
      compounds in S. verrucosa, which represented 84.64% of the total extract.
      However, the constituents of the cultured endophyte extract contained mainly
      acetic acid (35.05%), valeric acid, 3-methyl-, methyl ester (21.25%), and butane
      2, 3-diol (12.24%). Although the extracts of S. verrucosa and its endophyte
      showed little chemical composition correlation, both of them demonstrated
      antifungal and antitumor activities. Furthermore, C. fusiforme has displayed a
      wider range of antimicrobial and antitumor activities, which were better than the
      host plant. These results could support the suggestion of endophytes as an
      alternative of the host for medicinal activity.

PMID- 18830145
TI  - Synthesis of Schiff and Mannich bases of isatin derivatives with 4-amino-4,5
      dihydro-1H-1,2,4-triazole-5-ones.
AB  - Ethyl imidate hydrochlorides 1 were prepared by passing HCl gas through solutions
      of substituted benzyl cyanides and absolute ethanol. Ethoxycarbonylhydrazones 2
      were synthesized from the reaction of compounds 1 with ethyl carbazate. Treatment
      of 2 with hydrazine hydrate leads to the formation of substituted 4-amino-4,5
      dihydro-1H-1,2,4-triazole-5-ones 3. Isatin and 5-chloroisatin were added to 3 to
      form Schiff bases 4 and N-Mannich bases 5 of these compounds were synthesized by
      reacting with formaldehyde and piperidine. Their chemical structures were
      confirmed by means of IR, (1)H- and (13)C-NMR data and by elemental analysis.

PMID- 18830146
TI  - In vitro and in vivo evaluation of microparticulate drug delivery systems
      composed of macromolecular prodrugs.
AB  - Macromolecular prodrugs are very useful systems for achieving controlled drug
      release and drug targeting. In particular, various macromolecule-antitumor drug
      conjugates enhance the effectiveness and improve the toxic side effects. Also,
      polymeric micro- and nanoparticles have been actively examined and their in vivo
      behaviors elucidated, and it has been realized that their particle
      characteristics are very useful to control drug behavior. Recently, researches
      based on the combination of the concepts of macromolecular prodrugs and micro- or
      nanoparticles have been reported, although they are limited. Macromolecular
      prodrugs enable drugs to be released at a certain controlled release rate based
      on the features of the macromolecule-drug linkage. Micro- and nanoparticles can
      control in vivo behavior based on their size, surface charge and surface
      structure. These merits are expected for systems produced by the combination of
      each concept. In this review, several micro- or nanoparticles composed of
      macromolecule-drug conjugates are described for their preparation, in vitro
      properties and/or in vivo behavior.

PMID- 18830147
TI  - Antifilarial lead molecules isolated from Trachyspermum ammi.
AB  - Lymphatic filariasis is caused by infection with the parasitic filarial nematodes
      Wuchereria bancrofti, Brugia malayi and B. timori, transmitted by mosquitoes. The
      lack of an adulticidal drug poses a challenge to filariasis elimination, hence it
      is essential to develop an effective antifilarial drug which could either kill or
      permanently sterilize the adult worms. In the reported work the in vitro activity
      of a methanolic extract of fruits of Trachyspermum ammi (Apiaceae) against adult
      bovine filarial Setaria digitata worms has been investigated. A bioassay-guided
      fractionation was carried out by subjecting the crude extract to flash
      chromatography. HPLC analysis was done for the crude extract and active fraction.
      The crude extract and the active fraction showed significant activity against the
      adult S. digitata by both a worm motility and MTT [3-(4,5-dimethylthiazol-2-yl)
      2,5-diphenyltetrazolium bromide] reduction assays. The isolated active principle
      was chemically characterized by IR, (1)H-NMR and MS analysis and identified as a
      phenolic monoterpene. It was screened for in vivo antifilarial activity against
      the human filarial worm B. malayi in Mastomys coucha, showing macrofilaricidal
      activity and female worm sterility in vivo against B. malayi. The findings thus
      provide a new lead for development of a macrofilaricidal drug from natural
      products.

PMID- 18830148
TI  - Phytochemical contents and antioxidant capacities of two Aloe greatheadii var.
      davyana extracts.
AB  - Aloe greatheadii var. davyana (Asphodelaceae) is used among rural South African
      communities to treat arthritis, skin cancer, burns, eczema, psoriasis, digestive
      problems, high blood pressure and diabetes, despite very little supporting
      scientific evidence. Due to increased interest by both the scientific community
      and industry regarding the medicinal uses of this plant species, we identified,
      quantified and compared the phytochemical contents and antioxidant capacities of
      two extracts of A. greatheadii; a leaf gel extract (LGE) and a 95 % aqueous
      ethanol leaf gel extract (ELGE), using various modified extraction procedures, GC
      MS and spectrophotometry. Apart from extensively characterizing this medicinal
      plant with regards to its organic acid, polyphenols/phenolic acid, alcohol,
      aldehyde, ketone, alkane, pyrimidine, indole, alkaloid, phytosterol, fatty acid
      and dicarboxylic acid contents and antioxidant capacities, we describe a modified
      extraction procedure for the purpose of general phytochemical characterization,
      and compare this to a 95 % aqueous ethanol extraction technique. From the results
      it is clear that A. greatheadii contains a variety of compounds with confirmed
      antioxidant capacity and other putative health benefits (such as blood glucose,
      cholesterol and cortisol lowering properties) relating to the prevention or
      treatment of diabetes, cardiovascular disease, cancer and hypertension. The
      results also indicate that separate ethyl acetate/diethyl ether and hexane
      extractions of the LGE, better serve for general phytochemical characterization
      purposes, and 95 % aqueous ethanol extraction for concentrating selective groups
      of health related compounds, hence justifying its use for biological in vivo
      efficacy studies.

PMID- 18830149
TI  - Phytochemical analysis of the essential oil from botanically certified oleogum
      resin of Boswellia sacra (Omani Luban).
AB  - The yield of hydrodistillation of a botanically certified Oleogum Resin of
      Boswellia sacra essential oil (5.5%); and its chemical constituents were
      determined. The GC/MS technique was used for the analysis of the oil. Several oil
      components were identified based upon comparison of their mass spectral data with
      those of reference compounds published in literature or stored in a computer
      library. The oil was characterized by the high content of the monoterpenes (34)
      which constituted 97.3% in which E-beta-ocimene and limonene were the major
      constituents. The remaining 2.7% was accounted for the sesquiterpenes (16) in
      which the E-caryophyllene was the major constituent. The analysis proved the
      complete absence of the diterpenes.

PMID- 18830150
TI  - Polyphenols in cocoa and cocoa products: is there a link between antioxidant
      properties and health?
AB  - Cocoa and cocoa products have received much attention due to their significant
      polyphenol contents. Cocoa and cocoa products, namely cocoa liquor, cocoa powder
      and chocolates (milk and dark chocolates) may present varied polyphenol contents
      and possess different levels of antioxidant potentials. For the past ten years,
      at least 28 human studies have been conducted utilizing one of these cocoa
      products. However, questions arise on which of these products would deliver the
      best polyphenol contents and antioxidant effects. Moreover, the presence of
      methylxanthines, peptides, and minerals could synergistically enhance or reduce
      antioxidant properties of cocoa and cocoa products. To a greater extent, cocoa
      beans from different countries of origins and the methods of preparation (primary
      and secondary) could also partially influence the antioxidant polyphenols of
      cocoa products. Hence, comprehensive studies on the aforementioned factors could
      provide the understanding of health-promoting activities of cocoa or cocoa
      products components.

PMID- 18830151
TI  - Evaluation of flavonoids and furanocoumarins from Citrus bergamia (Bergamot)
      juice and identification of new compounds.
AB  - Bergamot juice (BJ) contains different classes of flavonoids (e.g. flavanones and
      flavones) that can exert beneficial effects on human health. The aim of this
      study was to evaluate the qualitative and quantitative composition of a BJ
      obtained from fruits harvested in Southern Italy (Calabria) at the end of their
      maturation period. The identity of several flavonoids and furanocoumarins was
      assessed by co-chromatography, UV spectra and molecular weight comparison. The
      unknown compounds were dissociated by induced collision (CID-MS) and their
      identity established through the characteristic ions product. By this approach a
      complete profile of about twenty compounds (furano-coumarins, flavonoids C- and O
      glycosides) present in BJ was obtained. Furthermore, three acylated flavanones,
      present in amounts of 20.1+/-1.1, 89.3+/-2.2 and 190.1+/-3.1 mg/L, respectively,
      and which seem to correspond to di-oxalate derivatives of neoeriocitrin, naringin
      and neohesperidin, were identified for the first time in BJ. The other main
      flavanones were naringin, neohesperidin and neoeriocitrin, and their content was
      167.5+/-1.8, 123.9+/-1.7 and 73.3+/-1.6 mg/L, respectively. Concerning flavones,
      the total amount in BJ was about 160 mg/L and the main ones were vicenin-2,
      stellarin-2, rhoifolin and neodiosmin. Bergapten and bergamottin were the primary
      furanocoumarins in BJ and their amounts were 9.0+/-0.4 and 18.2+/-0.5 mg/L,
      respectively.

PMID- 18830152
TI  - New triterpene glucosides from the roots of Rosa laevigata Michx.
AB  - Two new ursane-type triterpene glucosides, 2alpha,3alpha,24-trihydroxyurs-12,18
      dien-28-oic acid beta-D-glucopyranosyl ester (1) and 2alpha,3alpha,23
      trihydroxyurs-12,19(29)-dien-28-oic acid beta-D-glucopyranosyl ester (2), were
      isolated from the roots of Rosa laevigata, together with three known compounds:
      2alpha,3beta,19alpha-trihydroxyurs-12-en-28-oic acid beta-Dglucopyranosyl ester
      (3), 2alpha,3alpha,19alpha-trihydroxyurs-12-en-28-oic acid beta-D-glucopyranosyl
      ester (4) and 2alpha,3beta,19alpha,23-tetrahydroxyurs-12-en-28-oic acid beta-D
      glucopyranosyl ester (5). The structures of new compounds were established on the
      basis of detailed 1D and 2D NMR spectroscopic analyses. Compounds 2 and 5
      exhibited modest in vitro antifungal activities against Candida albicans and C.
      krusei.

PMID- 18830153
TI  - Design and synthesis of immunoconjugates and development of an indirect ELISA for
      rapid detection of 3, 5-dinitrosalicyclic Acid hydrazide.
AB  - In this study novel immunoconjugates were designed, synthesized and then used to
      develop a rapid, specific and sensitive indirect ELISA method to directly detect
      residues of 3,5-dinitrosalicyclic acid hydrazide (DNSH), a toxic metabolite of
      nifursol present in chicken tissues. The hapten DNSHA was first designed and used
      to covalently couple to BSA to form an immunogen which was immunized to rabbits
      to produce a polyclonal antibody against DNSH. Furthermore, a novel 3,5
      dinitrosalicylic acidovalbumin (DNSA-OVA) immunoconjugate structurally different
      from DNSHA-OVA was designed and used as a "substructural coating antigen" to
      improve the sensitivity of an indirect ELISA analysis for a direct DNSH
      detection. Based on the "substructural coating antigen" concept, an optimized
      indirect ELISA method was established that exhibited good specificity and high
      sensitivity for detecting DNSH, with a cross-reactivity of less than 0.1%
      (excluding the parent compound nifursol), IC(50) of 0.217 nmol/mL and detection
      limit of 0.018 nmol/mL. Finally, a simple and efficient analysis of DNSH samples
      in chicken tissues showed that the average recovery rate of the indirect ELISA
      analysis was 82.3%, with the average coefficient of variation 15.9%. Thus, the
      developed indirect ELISA method exhibited the potential for a rapid detection of
      DNSH residues in tissue.

PMID- 18830154
TI  - Effects of various drugs on alcohol-induced oxidative stress in the liver.
AB  - The major aim of this work was to investigate how alcohol-induced oxidative
      stress in combined chemotherapy changes the metabolic function of the liver in
      experimental animals. This research was conducted to establish how bromocriptine,
      haloperidol and azithromycin, applied to the experimental model, affected the
      antioxidative status of the liver. The following parameters were determined:
      reduced glutathione, activities of glutathione peroxidase, glutathione reductase,
      peroxidase, catalase, xanthine oxidase and lipid peroxidation intensity. Alanine
      transaminase was measured in serum. Alcohol stress (AO group) reduced glutathione
      and the activity of xanthine oxidase and glutathione peroxidase, but increased
      catalase and alanine transaminase activity. The best protective effect was
      achieved with the bromocriptine (AB1 group), while other groups had similar
      effects on the studied parameters.

PMID- 18830155
TI  - Useful spectrokinetic methods for the investigation of photochromic and thermo
      photochromic spiropyrans.
AB  - This review reports on the main results of a set of kinetic elucidation methods
      developed by our team over the last few years. Formalisms, procedures and
      examples to solve all possible AB photochromic and thermophotochromic kinetics
      are presented. Also, discussions of the operating conditions, the continuous
      irradiation experiment, the spectrokinetic methods testing with numerical
      integration methods, and the identifiability/distinguishability problems, are
      included.

PMID- 18830156
TI  - Isoquinoline alkaloids isolated from Corydalis yanhusuo and their binding
      affinities at the dopamine D1 receptor.
AB  - Bioactivity-guided fractionation of Corydalis yanhusuo has resulted in the
      isolation of eight known isoquinoline alkaloids - tetrahydropalmatine,
      isocorypalmine, stylopine, corydaline, columbamine, coptisin, 13-methylpalmatine,
      and dehydrocorybulbine. The tertiary alkaloids were further analyzed by chiral
      HPLC to determine the ratios of d-and l-isomers. The isolated compounds were
      screened for their binding affinities at the dopamine D(1) receptor.
      Isocorypalmine had the highest affinity (K(i) = 83 nM). The structure-affinity
      relationships of these alkaloids are discussed.

PMID- 18830157
TI  - Efficient TCT-catalyzed synthesis of 1,5-benzodiazepine derivatives under mild
      conditions.
AB  - 2,4,6-Trichloro-1,3,5-triazine (TCT) efficiently catalyzed the condensation
      reactions between 1,2-diamines and various enolizable ketones to afford 1,5
      benzodiazepines in good to excellent yields. Simple and mild reaction conditions,
      the use of a cheap catalyst and easy workup and isolation are notable features of
      this method.

PMID- 18830158
TI  - Imidazole-based potential Bi- and tridentate nitrogen ligands: synthesis,
      characterization and application in asymmetric catalysis.
AB  - Twelve new imidazole-based potential bi- and tridentate ligands were synthesized
      and characterized. Whereas in the first series the alpha-amino acid and imidazole
      moieties were linked by an amino bond, in the second series the tridentate
      ligands, containing two imidazole groups, were separated by an amide bond. The
      first series was obtained by the reductive amination of 2-phenylimidazole-4
      carboxaldehyde with alpha-amino acid esters. The tridentate ligands were prepared
      from 2-phenylimidazole-4-carboxylic acid and chiral amines. In the Henry
      reaction, the amines were revealed as a more reactive species than the less
      nucleophilic amides, however the enantiomeric excesses were generally poor.

PMID- 18830159
TI  - Novel strategies to improve the anticancer action of 5-fluorouracil by using drug
      delivery systems.
AB  - Because of the fundamental importance of new therapeutic routes for cancer
      treatment, a number of systems based on colloidal particles as vehicles for the
      delivery of the anticancer drug 5-fluorouracil have been devised. The target is
      always to provide the proper dose of the antitumor agent only at the desired
      locus of action, thus reducing the unwanted side effects. In this review, the
      main strategies and the more significant results in the development of 5
      fluorouracil carriers for cancer treatment are discussed.

PMID- 18830161
TI  - Antibacterial properties of 3 H-spiro[1-benzofuran-2,1'-cyclohexane] derivatives
      from Heliotropium filifolium.
AB  - A re-examination of cuticular components of Heliotropium filifolium allowed the
      isolation of four new compounds: 3'-hydroxy-2',2',6'-trimethyl-3H-spiro[1-benzo
      furan-2,1'-cyclohexane]-5-carboxylic acid(2), methyl 3'-acetyloxy-2',2',6'
      trimethyl-3H-spiro[1-benzofuran-2,1'-cyclohexane]-5-carboxylate (3), methyl 3'
      isopentanoyloxy-2',2',6'-trimethyl-3H-spiro[1-benzofuran-2,1'-cyclohexane]-5
      carboxylate (4) and methyl 3'-benzoyloxy-2',2',6'-trimethyl-3H-spiro[1-benzofuran
      2,1'-cyclohexane]-5-carboxylate (5).Compounds 2-5 were identified by their
      spectroscopic analogies with filifolinol (1), and their structures confirmed by
      chemical correlation with 1. The antimicrobial properties of the compounds were
      tested against Gram positive and Gram negative bacteria. Some of them proved to
      be active against Gram positive, but inactive against Gram negative bacteria. In
      searching for structure-activity relationships from the obtained MIC values,
      lipophilicity was shown to be an important variable.

PMID- 18830160
TI  - Radiation- and photo-induced activation of 5-fluorouracil prodrugs as a strategy
      for the selective treatment of solid tumors.
AB  - 5-Fluorouracil (5-FU) is used widely as an anticancer drug to treat solid
      cancers, such as colon, breast, rectal, and pancreatic cancers, although its
      clinical application is limited because 5-FU has gastrointestinal and
      hematological toxicity. Many groups are searching for prodrugs with functions
      that are tumor selective in their delivery and can be activated to improve the
      clinical utility of 5-FU as an important cancer chemotherapeutic agent. UV and
      ionizing radiation can cause chemical reactions in a localized area of the body,
      and these have been applied in the development of site-specific drug activation
      and sensitization. In this review, we describe recent progress in the development
      of novel 5-FU prodrugs that are activated site specifically by UV light and
      ionizing radiation in the tumor microenvironment. We also discuss the chemical
      mechanisms underlying this activation.

PMID- 18830162
TI  - Methyl mercapturate synthesis: an efficient, convenient and simple method.
AB  - A safe and simple method for methyl S-arylmercapturate synthesis is described.
      Thirteen such compounds, to be used afterwards in metabolism studies, have been
      obtained with yields ranging from 71 to 99.6%. These compounds were obtained
      using a sulfa-Michael addition and synthesized by adding the corresponding
      thiophenols to a mixture composed of methyl 2-acetamidoacrylate (MAA), potassium
      carbonate and a phase transfer catalyst, Aliquat 336. MAA, the initial synthon,
      was itself isolated in quasi quantitative yield following a fully described
      synthesis.

PMID- 18830163
TI  - Molecular weight and monosaccharide composition of Astragalus polysaccharides.
AB  - Two polysaccharides (APS-I and APS-II) were isolated from the water extract of
      Radix Astragali and purified through ethanol precipitation, deproteination and by
      ion-exchange and gel-filtration chromatography. Their molecular weight was
      determined using high performance liquid chromatography and gel permeation
      chromatography (HPLC-GPC) and their monosaccharide composition was analyzed by
      TLC and HPLC methods, using a refractive index detector (RID) and an NH(2)
      column. It was shown that APS-I consisted of arabinose and glucose and APS-II
      consisted of rhamnose, arabinose and glucose, in a molar ratio of 1:3.45 and
      1:6.25:17.86, respectively. The molecular weights (Mw) of APS-I and APS-II were
      1,699,100 Da and 1,197,600 Da, respectively.

PMID- 18830164
TI  - Characterization of hydrocortisone biometabolites and 18S rRNA gene in
      Chlamydomonas reinhardtii cultures.
AB  - A unicellular microalga, Chlamydomonas reinhardtii, was isolated from rice paddy
      field soil and water samples and used in the biotransformation of hydrocortisone
      (1). This strain has not been previously tested for steroid bioconversion.
      Fermentation was carried out in BG-11 medium supplemented with 0.05% substrate at
      25 degrees C for 14 days of incubation. The products obtained were
      chromatographically purified and characterized using spectroscopic methods.
      11b,17 beta-Dihydroxyandrost-4-en-3-one (2), 11 beta-hydroxyandrost-4-en-3,17
      dione (3), 11 beta,17 alpha,20 beta,21-tetrahydroxypregn-4-en-3-one (4) and
      prednisolone (5) were the main products of the bioconversion. The observed
      bioreaction features were the side chain degradation of the substrate to give
      compounds 2 and 3 and the 20-ketone reduction and 1,2-dehydrogenation affording
      compounds 4 and 5, respectively. A time course study showed the accumulation of
      product 2 from the second day of the fermentation and of compounds 3, 4 and 5
      from the third day. All the metabolites reached their maximum concentration in
      seven days. Microalgal 18S rRNA gene was also amplified by PCR. PCR products were
      sequenced to confirm their authenticity as 18S rRNA gene of microalgae. The
      result of PCR blasted with other sequenced microalgae in NCBI showed 100%
      homology to the 18S small subunit rRNA of two Chlamydomonas reinhardtii spp.

PMID- 18830165
TI  - Discovery of a novel CCR5 antagonist lead compound through fragment assembly.
AB  - CCR5, as the major co-receptor for HIV-1 entry, is an attractive novel target for
      the pharmaceutical industry in the HIV-1 therapeutic area. In this study, based
      on the structures of maraviroc and 1,4-bis(4-(7-chloroquinolin-4-yl)piperazin-1
      yl)butane-1,4-dione (1), which was identified using structure-based virtual
      screening in conjunction with a calcium mobilization assay, a series of novel
      small molecule CCR5 antagonists have been designed and synthesized through
      fragment assembly. Preliminary SARs were obtained, which are in good agreement
      with the molecular binding model and should prove helpful for future antagonist
      design. The novel scaffold presented here might also be useful in the development
      of maraviroc-derived second generation CCR5 antagonists.

PMID- 18830167
TI  - Malignant mental nerve neuropathy: systematic review.
AB  - Malignant mental neuropathy (MMN) is a neurological manifestation of cancer,
      characterized by the presence of hypoesthesia or anesthesia restricted to the
      territory of the mental branch of the mandibular nerve. A systematic review of
      the literature has been made on MMN, analyzing the etiology, pathogeny, clinical
      characteristics, complementary tests and the prognosis. Sixteen studies,
      providing 136 cases were selected. Breast cancer and lymphomas were the most
      frequently associated malignant diseases. The most frequent pathogenic mechanisms
      producing neurological involvement were: peripherally, mandibular lesions; and
      centrally, tumors at the base of the cranium. Regarding clinical characteristics,
      manifestation of MMN was the primary symptom of malignant disease in 27.7% of
      cases, and a first symptom of recurrence in 37.7%. The group of selected studies
      included 50 orthopantomographs, 9 mandibular computed tomographies and 50
      radiographic examinations of the cranial region. The most affected region was the
      mandible. The appearance of MMN is an ominous prognosis for the progression of
      the disease, with a mortality of 78.5% within a mean of 6.9 months.

PMID- 18830166
TI  - Design and synthesis of bis-amide and hydrazide-containing derivatives of malonic
      acid as potential HIV-1 integrase inhibitors.
AB  - HIV-1 integrase (IN) is an attractive and validated target for the development of
      novel therapeutics against AIDS. In the search for new IN inhibitors, we designed
      and synthesized three series of bis-amide and hydrazide-containing derivatives of
      malonic acid. We performed a docking study to investigate the potential
      interactions of the title compounds with essential amino acids on the IN active
      site.

PMID- 18830168
TI  - Pemphigus vulgaris in oral cavity: clinical analysis of 71 cases.
AB  - OBJECTIVE: The purpose of the study was to evaluate the clinical presentation of
      pemphigus vulgaris in the oral cavity. STUDY DESIGN: A retrospective study of 71
      cases of pemphigus vulgaris obtained over a period of 7 years from 1st January
      2001 to 31st December 2007 in the Department of Oral Pathology, Government Dental
      College and Department of Dermatology, Government Medical College, Calicut was
      designed. Clinical details such as age, sex, intraoral distribution, extent of
      oral lesions, oral presentation, duration, oral involvement (whether primary or
      secondary) and mode of onset were noted from the files of corresponding
      Departments. RESULTS: In about 53.52% of cases, the oral cavity was the primary
      site of involvement. The mean age was 42.73 years and male: female ratio was
      1:1.73. The most commonly affected sites were the buccal mucosa and the palate.
      The disease began with generalized lesions rather than localized lesions. All
      cases presented as ulcers or erosions. CONCLUSION: Although minor differences
      were noted, the results of this study are in relatively good agreement with the
      literature with regard to the age, gender, and initial presentation of pemphigus
      vulgaris.

PMID- 18830169
TI  - Infected lingual osseous choristoma. Report of a case and review of the
      literature.
AB  - Osseous choristoma is a rare, benign lesion of the oral cavity occurring usually
      in the tongue. It appears as a tumorous mass of normal bony structure with mature
      cells in an ectopic position. The case of a 72 years Caucasian male is presented
      and analyzed along with 52 similar cases reported in the English literature
      between 1967 and 2007. Lingual choristoma shows a female predilection, whereas
      the commonest anatomic location is the posterior third of the tongue, occurring
      at or close to the foramen caecum and the circumvallate papillae. Histologically
      the lesions show signs of a well-circumscribed mass of vital bone located under
      the surface oral epithelium. Some lesions represent developmental malformations,
      whereas others may be reactive lesions after trauma or chronic irritation.
      Treatment of lingual osseous choristoma consists of simple excision.

PMID- 18830170
TI  - Pycnodysostosis. A report of 3 clinical cases.
AB  - Pycnodysostosis is a rare clinical entity, first described in 1962 by Maroteaux
      and Lamy. It is a genetic disorder, usually diagnosed at an early age. However,
      the diagnosis is sometimes late, made as a result of bone fracture, given the
      severe bone fragility resulting from increased bone density. Oral and
      maxillofacial manifestations of this disease are very clear. The head is usually
      large, the nose beaked, the mandibular angle obtuse, and both maxilla and
      mandible hypoplastic. Dental abnormalities and impaction are observed, as well as
      alterations in eruption and frequent dental crowding. The differential diagnosis
      is established with osteopetrosis, cleidocranial dysplasia and idiopathic acro
      osteolysis. This article reviews the clinical and radiographic characteristics of
      pycnodysostosis based on three clinical cases of patients with this disease.

PMID- 18830171
TI  - Analysis of the histopathological artefacts in punch biopsies of the normal oral
      mucosa.
AB  - OBJECTIVES: To study the most frequent artifacts of punch biopsies of the healthy
      oral mucosa, distinguishing between those attributable to the surgical technique
      and those resulting from sample processing in the laboratory. STUDY DESIGN: A
      total of 186 samples of oral mucosa (dorsal lingual mucosa) were obtained from
      186 adult albino rats by the experienced oral surgeons, evaluating the presence
      of artifacts attributable to the surgical technique (crush, splits,
      fragmentation, pseudocysts and haemorrhage) and those attributable to sample
      processing in the laboratory (orientation). RESULTS: The distribution of
      artifacts attributable to the surgical procedure was as follows: crush 16.67%,
      splits 0%, fragmentation 0%, pseudocysts 1.08% and hemorrhage 0%. The artifacts
      corresponding to sample processing in the laboratory (orientation) represented
      37.63%. CONCLUSIONS: The present study shows use of the punch for obtaining
      biopsies of the healthy oral mucosa to produce few artifacts. In addition, good
      or poor orientation of the samples is not attributable to the surgical technique
      but to processing of the samples in the laboratory.

PMID- 18830172
TI  - Beckwith Wiedemann syndrome: presentation of a case report.
AB  - Beckwith Wiedemann Syndrome (BWS) is a rare congenital disease of low prevalence.
      However, it presents a high prevalence within the genetic pathologies of
      overgrowth. This syndrome presents typical manifestations such as macroglossia,
      macrosomy at birth, omphalocele and defects of the anterior abdominal wall. Its
      origin is known to be genetic, but its mechanism of generation is not clear. This
      syndrome has been the object of wide studies since investigators have established
      a relationship between the methods of assisted fertilization (assisted
      reproduction treatment, ART) and its appearance. Currently, research is oriented
      towards the improvement of the prenatal diagnostic techniques, which would allow
      a preparation of the multidisciplinary medical team to treat the pathologies with
      which these patients are born. Next we present the case of a 1 year-old child who
      consults this service with a diagnosis of macroglossia associated with BWS.

PMID- 18830173
TI  - Dental management of oral self-mutilation in neurological patients: a case of
      congenital insensitivity to pain with anhidrosis.
AB  - Hereditary sensory and autonomic neuropathy type IV is a rare disease
      characterized by fever episodes, mental retardation of different intensity,
      recurrent episodes of fever secondary to anhidrosis, little or no perspiration
      and congenital insensitivity to pain. Oral self-mutilation is also a
      characteristic sign. In this article, we present the case of an infant, aged 22
      months, who showed these clinical characteristics and was treated with a dental
      device to prevent the patient from injuring her tongue. This device consisted of
      two acrylic splints joined at the back in the posterior sector, it provided an
      anterior open bite and allowed the infant to breathe through her mouth. The
      lesions of the patient had improved after using the device but the patient died
      due to the medical problem. Neuropathies treatment is a great challenge for
      medical teams. Dentists should form part ot these teams because of the bucal
      implications that may appear. Different appliances can be designed in order to
      solve the special problems each case may present.

PMID- 18830174
TI  - Analgesic action of laser therapy (LLLT) in an animal model.
AB  - OBJECTIVES: To evaluate the analgesic effect of laser therapy on healthy tissue
      of mice. STUDY DESIGN: Forty-five animals were divided in three groups of 15: A-
      infrared laser irradiation (830 nm, Kondortech, Sao Carlos, SP, Brazil); B--red
      laser irradiation (660 nm, Kondortech, Sao Carlos, SP, Brazil); C-- ham
      irradiation with laser unit off. After laser application, the mice remained
      immobilized for the injection of 30 microl of 2% formalin in the plantar pad of
      the irradiated hind paw. The time that the mouse kept the hind paw lifted was
      measured at 5 min intervals for 30 minutes. RESULTS: Results showed statistically
      significant differences comparing the control group with the infrared laser group
      at 5, 20, 25 and 30 accumulated minutes, and with the red laser group at all time
      points. The analysis of partial times, at each 5 minutes, showed statistically
      significant differences between the control and the laser groups up to 20
      minutes. CONCLUSIONS: Laser therapy had an analgesic effect and red laser had the
      best results.

PMID- 18830175
TI  - Benign fibro-osseous lesions of the maxillas: analysis of 11 cases.
AB  - INTRODUCTION: A study is made of the principal characteristics of the oral
      lesions biopsied in our Service of Oral Surgery and histologically diagnosed as
      corresponding to fibro-osseous lesions of the maxillas. PATIENTS AND METHODS: A
      retrospective review was made of all the biopsies made in a Service of Oral
      Surgery between 1996 and 2003. The reason for consultation was analyzed, along
      with patient age, sex, clinical and radiological characteristics, tentative
      diagnosis, histological diagnosis and treatment provided. RESULTS: A total of
      1238 biopsies were performed during the study period. Of these, only 11
      corresponded to benign fibro-osseous lesions (7 women and 4 men). The mean
      patient age was 44 years (range 19-72 years). The most frequent location was the
      mandible (8 of the cases). In 7 patients the lesions constituted casual
      radiological findings; 4 presented bulging of the vestibular cortical bone,
      though only one of them reported pain. The histological diagnoses comprised 7
      cemento-ossifying fibromas and 4 fibrous dysplasias. In 9 cases surgical
      resection was carried out, while in one case an incisional biopsy was performed,
      and in the remaining case curettage was decided. DISCUSSION: These lesions are
      more frequent in women than in men, and the age at presentation is variable. In
      terms of lesion location, fibrous dysplasia is more common in the upper maxilla,
      while cemento-ossifying fibroma is more frequently found in the mandible. The
      diagnosis of such lesions is established upon contrasting the data obtained from
      the anamnesis, physical examination, the radiological characteristics, the
      intraoperative findings and the histological study, since both disorders have
      similar clinical and histological features--despite the fact that they constitute
      distinct disease conditions.

PMID- 18830176
TI  - Intraosseous foreign-body granuloma in the mandible subsequent to a 20-year-old
      work-related accident.
AB  - The purpose of this article was to describe the clinical and microscopic features
      of an intraosseous foreign-body granuloma in the mandible that developed after
      the traumatic implantation of metal fragments during a work-related accident. A
      65-year-old male patient had a severe pain in the body of mandible. Clinical
      examination showed facial asymmetry and a scar, extending to the left mental
      region. Intraoral examination revealed a soft mass involving the left alveolar
      bone with normal appearance of the mucosa surface. Panoramic radiographs showed a
      radiolucent lesion along the mandible extending from the central incisive to the
      first molar. Computed tomography revealed an osteolytic mass in the same area.
      His medical history included a work-related accident twenty years prior to
      evaluation. During the biopsy an important amount of bright metal-like pieces
      surrounded by soft tissue were found. A microscopic examination showed a foreign
      body associated with an aggregation of multinucleated giant cells. The final
      diagnosis was a foreign body granuloma. Even though foreign-body granulomas in
      the mandible are rare lesions, dentists should be familiar with their features
      and include them in the differential diagnosis of tissue masses.

PMID- 18830177
TI  - Software applied to oral implantology: update.
AB  - Software in combination with imaging techniques is used increasingly for
      diagnosis, planning and treatment in oral implantology. Computer-aided surgery
      allows a great accuracy in implant positioning to be obtained, taking advantage
      of the amount of bone available and facilitating minimally invasive surgery. It
      is a significant aid in determining implant number, location, angle and
      characteristics. A CT with a radiographic template positioned in the mouth is
      made for the patient. Data are stored on a CD in DICOM 3 format and then
      introduced in the computer where implant treatment will be planned, using the
      chosen software. Navigation improves surgical accuracy through the aid of
      software based on the images captured from CT or MRI and a surgical instrument
      tracking system. Infrared light-emitting diodes are connected to rotatory
      instruments and to the patientvs template. Information is collected by special
      purpose cameras, allowing the procedure to be viewed in real time on a monitor.
      It is useful in situations where an exact implantation is demanded, such as
      anatomical limitations, little space, atrophic maxillae, sinus lifts or zygomatic
      implants. Articles reviewed agree in emphasizing the reliability and accuracy of
      the planning and computer-assisted navigation systems available in the market.
      Nevertheless, many applications are still in the development phase.

PMID- 18830178
TI  - Local flap reconstruction of large scalp defects.
AB  - Scalp defects can have a number of origins, and their repair is dependent upon
      their location, size and depth. In the case of the scalp, the repair of even
      small defects is complicated. Local flaps are the reference for the
      reconstruction of such defects. Knowledge of scalp anatomy is essential for
      preparing these flaps, which must be based on one or two vascular pedicles to
      afford a large rotation angle--thereby facilitating closure of the defect. The
      parietal zone is the location offering the greatest flap mobilization
      possibilities. We present a case involving the repair of a major pericranial
      frontoparietal scalp defect. A local transverse posterior transpositioning scalp
      flap was raised with the posterior auricular and occipital arteries as vascular
      pedicle. Following repositioning of the flap, a free partial-thickness skin graft
      from the thigh was used to cover the donor zone. A review is provided of the
      different techniques for the reconstruction of large scalp defects.

PMID- 18830179
TI  - Prevalence of smoking among dentists in Catalonia--Spain (2006) . Literature
      review of smoking cessation practices in the dental office.
AB  - OBJECTIVE: The objective of this study was to collect data on the prevalence of
      smokers among Catalonian dentists (by age and sex) and compare them with existing
      data on the general population, doctors, registered nurses and pharmacists. The
      overall prevalence of smokers in Catalonia (2006) was 34.5% of men and 24.3% of
      women. Data available on the prevalence of smoking among doctors (26.3% men and
      22.1% women), pharmacists (19.8% men and 20.6% women) and registered nurses
      (34.1% men and 35.3% women) relates to the year 2002. STUDY DESIGN: In September
      2006, Catalonian dentists (n=3,799) were asked about their habits in relation to
      tobacco in a self-administered questionnaire, on use and opinions with respect to
      dental amalgam. Five hundred and seventy-nine questionnaires were received, of
      which 538 answered the question on smoking (14.2% of the sample universe).
      RESULTS: The prevalence of smokers among dentists is lower (24.9% of men and
      18.4% of women) than in the general population and other healthcare
      professionals. In dentists in the age group between 25 and 34 years, the
      prevalence was 26.1% in men and 14.9% in women, while the prevalence in this age
      group in the general population was 43.6% and 37.1%, respectively. CONCLUSION:
      Catalonian dentists have a much lower prevalence of tobacco use than the general
      population and lower even than other healthcare professionals. Given that non
      smoking healthcare professionals have better awareness for providing
      recommendations for smoking prevention and cessation, Catalonian dentists may be
      a valid group for performing this task for which there is scientific evidence.

PMID- 18830180
TI  - Use of mineral trioxide aggregrate in the non-surgical repair of perforating
      invasive cervical resorption.
AB  - Mineral trioxide aggregate (MTA) has shown potential as a repair material for
      perforations. This clinical case demonstrates that when MTA was used as a repair
      material for root perforation due to invasive cervical resorption, the tooth was
      well in function for 27 months. Both clinical and radiographic follow-up showed a
      stable condition without any probing defect, ongoing root resorption, or apical
      pathosis.

PMID- 18830181
TI  - Effects of cruciferous allyl nitrile on phase 2 antioxidant and detoxification
      enzymes.
AB  - BACKGROUND: High intake of cruciferous vegetables has been associated with lower
      risk of various cancers, and the cancer preventive effect of the vegetables has
      been associated with their high levels of glucosinolates. The hydrolysis of
      glucosinolates results in the generation of bioactive compounds, including allyl
      nitrile which we previously found to be an active inducer of some phase 2
      enzymes. In this study, we further explored the inductive ability of this nitrile
      in light of increasing evidence that antioxidants delay or prevent the
      development of cancer. MATERIAL/METHODS: Groups of 6 mice were administered
      subtoxic doses of allyl nitrile (5, 50, 100 or 200 micromol/kg) or vehicle
      distilled water daily for 5 days by gastric intubation. On the sixth day, the
      animals were sacrificed for examination of enzyme activities in their tissues.
      Enzymes tested were thioredoxin reductase (TR), glutathione peroxidase (GPx),
      glutathione reductase (GR) and catalase. RESULTS: Allyl nitrile increased the
      activity of TR in the liver, kidneys and rectum at doses of 100-200
      micromol/kg/day, and GPx in the kidneys and small intestine at 50 to 200
      micromol/kg/day, while in the colon, alone, it decreased the activities of GR and
      catalase at doses of 200 and 100-200 micromol/kg/day, respectively not.
      CONCLUSIONS: The present results suggest an involvement of allyl nitrile in
      antioxidant defense in the body, except for the colon.

PMID- 18830182
TI  - Phasic coronary blood flow patterns in dogs vs. pigs: an acute ischemic heart
      study.
AB  - BACKGROUND: Canine and porcine hearts have been widely used to investigate
      diagnoses, interventions, and surgical therapies for ischemic heart disease. Dogs
      and pigs are known to vary with regard to the anatomic distribution of their
      coronary arteries. However, the mechanisms of these differences and the differing
      phasic coronary blood flow patterns between the two species are not well
      characterized. MATERIAL/METHODS: Phasic coronary blood flow patterns and
      hemodynamic data were analyzed using three flow probes placed around the left
      anterior descending (LAD), left circumflex (LCX), and right coronary (RCA)
      arteries in both canine and porcine models. RESULTS: Systolic left ventricular
      pressure, arterial pressure, and systemic vascular resistance in dogs were higher
      than in pigs. Likewise, total coronary blood flow, LAD flow, and LCX flow were
      higher in dogs than in pigs. LCX flow was higher in dogs, but RCA flow was higher
      in pigs. Diastolic fraction and diastolic/systolic peak velocity ratio of the
      LAD, LCX, and RCA showed no significant differences at baseline between dogs and
      pigs. Systolic LAD flow in dogs decreased after the creation of an LAD stenosis,
      whereas systolic LAD flow in pigs increased. CONCLUSIONS: Coronary blood flow
      patterns in dogs and pigs are quite different. These findings are potentially
      relevant to understanding the physiology of myocardial blood perfusion in dogs
      and pigs with ischemic heart disease.

PMID- 18830183
TI  - Effects of transplanting olfactory ensheathing cells on recovery of olfactory
      epithelium after olfactory nerve transection in rats.
AB  - BACKGROUND: Olfactory ensheathing cells (OECs) can remyelinate injured spinal
      cord and the peripheral nerve system, but little is known about its effect on the
      transected olfactory nerve. We investigated recovery of olfactory epithelium
      after transplanting allogeneic OECs in transected rat olfactory nerves.
      MATERIAL/METHODS: Olfactory ensheathing cells from the olfactory bulb were
      cultured in DMEM/F-12 medium and purified with cytosine arabinoside (Ara-c).
      Forty Sprague-Dawley rats were divided into 2 groups; the left olfactory nerve
      was transected in all animals. In the transplant group, DiI-labeled OECs were
      injected into the gap between the dura and the cribriform plate (n=24); DMEM/F-12
      medium was injected in control animals (n=16). Rats were subsequently killed for
      histologic examination. Olfactory evoked potentials (OEPs) were used to evaluate
      nerve conduction. RESULTS: After transecting the olfactory nerve, there was no
      horseradish peroxidase staining in the olfactory bulb; some OEPs disappeared.
      Five days after surgery, there was no horseradish peroxidase staining in the
      olfactory bulb of any animal. Apoptotic cells appeared in the epithelium; the
      thickness and cell number of the olfactory epithelium were decreased. Two weeks
      later, the thickness and cell number of the olfactory epithelium increased
      gradually. Some horseradish peroxidase staining in the olfactory bulb and OECs
      was detected; more growth associated protein-43 marked olfactory receptor neurons
      were visible. Six weeks after surgery, the cell number was greater in the
      transplant group (P<0.05); there was no statistically significant between-group
      difference regarding olfactory epithelium thickness. CONCLUSIONS: Transplanted
      OECs may be used to treat transected olfactory nerves.

PMID- 18830184
TI  - Sildenafil citrate on the inducibility of ventricular fibrillation and upper
      limit of vulnerability in swine.
AB  - BACKGROUND: Sildenafil citrate at supratherapeutic levels has been reported to
      decrease defibrillation efficacy. However, its effects on ventricular
      fibrillation induction and the upper limit of vulnerability (ULV) have not been
      investigated. We tested the hypothesis that sildenafil citrate reduces the
      ventricular fibrillation threshold (VFT) and increases the ULV. MATERIAL/METHODS:
      Twenty-one pigs (25-30 kg) were randomly assigned into 3 groups of 7 pigs each. A
      solution containing 100 mg (group 100) or 50 mg (group 50) sildenafil citrate or
      100 cc saline (group control) was infused intravenously in each pig. A train of
      10 S1s was delivered from an RV electrode, and an S2 stimulus was delivered at
      the peak of the T wave of the last S1 activation to determine the VFT and ULV,
      before and after drug administration. RESULTS: The 100 mg sildenafil citrate
      significantly (P<0.03) decreased VFT, accounting for approximately 36% by peak
      voltage and approximately 52% by total energy, and significantly (P<0.009)
      increased ULV, accounting for approximately 28% by peak voltage, and
      approximately 56% by total energy. CONCLUSIONS: Supratherapeutic concentrations
      of sildenafil citrate significantly decreased the VFT and increased the ULV,
      resulting in an expansion of the VF induction window during the vulnerable
      period.

PMID- 18830185
TI  - Mupirocin resistance among Iranian isolates of Staphylococcus aureus.
AB  - BACKGROUND: The topical agent mupirocin plays a crucial role in strategies
      designed to control outbreaks of methicillin-resistant Staphylococcus aureus. The
      rate of high- and low-level mupirocin resistance among S. aureus strains from
      Iranian hospitals is not known. MATERIAL/METHODS: Two hundred twenty-two
      nonduplicate S. aureus strains consecutively isolated in four university
      hospitals in Tehran, Iran, were tested for mupirocin susceptibility by disc
      diffusion agar method and minimum inhibitory concentration (MIC) determination by
      the E-test. Susceptibility to 16 other antimicrobial agents was also determined.
      RESULTS: With the disc diffusion agar method, the majority of strains (97.3%)
      were susceptible to mupirocin and only 2.7% were resistant. The S. aureus strains
      showed high resistance (>50%) to most antibiotics, including penicillin G,
      ampicillin-sulbactam, oxacillin, cefoxitin, ciprofloxacin, erythromycin,
      tetracycline, clindamycin, gentamicin, and rifampicin, but resistance to
      linezolid, chloramphenicol, cotrimoxazole, and quinupristin/dalfopristin was low
      and no isolate was resistant to vancomycin. In the E-test, six strains had MICs
      of >4 mg/l, i.e. five strains had MICs of 8-256 mg/l (low-level mupirocin
      resistance) and one strain had 1024 mg/l (high-level mupirocin resistance). One
      strain was resistant to mupirocin in the disc diffusion agar method but showed
      sensitivity in the E-test (MIC: 0.94 mg/l). The mupirocin-resistant S. aureus
      isolates were all methicillin resistant and more resistant to the other
      antimicrobial agents compared with the mupirocin-susceptible strains.
      CONCLUSIONS: This study is the first report about mupirocin resistance of S.
      aureus in Iranian hospitals.

PMID- 18830186
TI  - A new reversible ischemic neurologic deficit model in dogs.
AB  - BACKGROUND: The aim of this study was to produce an internal carotid artery (ICA)
      occlusion model in dogs that can be used for studying the effects of surgical
      revascularization procedures. MATERIAL/METHODS: After left frontoparietal
      craniectomy, the ICA and arterial circle of the brain were coagulated and
      transected, letting the middle cerebral artery be perfused by the contralateral
      ICA by way of the rostral cerebral artery in five mongrel dogs. Magnetic
      resonance imaging (MRI) and brain single-photon emission computed tomography
      (SPECT) were performed during the first 24 to 48 hours and 7 to 10 days after the
      operation. Paired t and Wilcoxon matched pair tests were used for statistics
      (p<0.05). RESULTS: All the dogs had postoperative hemiparesis that returned to
      normal after 7 to 10 days. Early MRI showed cerebral ischemia in the left
      parietal cortical area extending to the subcortical white matter, sparing the
      basal ganglion and the internal capsule. Early brain SPECT demonstrated
      hypoperfusion corresponding to the same area. This area became significantly
      restricted to a small cortical area in late MRI and SPECT images (p<0.05).
      CONCLUSIONS: It is concluded that, as symptoms resolved spontaneously, this model
      can be used as a "reversible ischemic neurological deficit" model for diagnostic
      imaging and pharmacological studies.

PMID- 18830187
TI  - Methylation of the MGMT and p16 genes in sporadic colorectal carcinoma and
      corresponding normal colonic mucosa.
AB  - BACKGROUND: Colorectal cancer, one of the most aggressive cancers, occurs with a
      high incidence in most countries. The usual treatment is surgery and subsequent
      chemotherapy and radiotherapy. Cancer development and progression is dictated by
      series of alterations in genes such as tumor suppressor genes, DNA repair genes,
      oncogenes and others. In colorectal carcinogenesis disturbances different from
      mutations called an epigenetic regulation are also taken into consideration.
      Epigenetics is defined as a modifications of the genome, heritable during cell
      division, which do not involve a change in the DNA sequence. In our study we
      analyzed methylation of CpG islands in the MGMT and p16 genes in sporadic
      colorectal cancers and normal corresponding colonic mucosa. MATERIAL/METHODS:
      Fresh tissue samples were obtained from 68 patients (age of 23 to 81 years) with
      primary colorectal adenocarcinoma and corresponding normal tissues. We used
      methylation-specific polymerase chain reaction (MSP) for analysis of the
      methylation status of MGMT and p16. RESULTS: Methylation of MGMT and p16 was
      detected in 59% and 53% of tumors, respectively. In corresponding normal colonic
      mucosa methylation of MGMT was detected in 20% and p16 in 18%. The normal colon
      mucosa obtained from younger patients (age of <65 years) showed less methylation
      frequency as compared with the normal mucosa from the older ones (age of >65
      years). CONCLUSIONS: The older age and female gender are generally associated
      with higher methylation levels for most CpG islands in normal colonic mucosa.
      These results indicate that MGMT and/or p16 aberrant methylation may play an
      important role in colorectal cancer.

PMID- 18830188
TI  - Dissociative symptoms and neuroendocrine dysregulation in depression.
AB  - BACKGROUND: Dissociative symptoms are traditionally attributed to psychological
      stressors that produce dissociated memories related to stressful life events.
      Dissociative disorders and dissociative symptoms including psychogenic amnesia,
      fugue, dissociative identity-disorder, depersonalization, derealization and other
      symptoms or syndromes have been reported as an epidemic psychiatric condition
      that may be coexistent with various psychiatric diagnoses such as depression,
      schizophrenia, borderline personality disorder or anxiety disorders. According to
      recent findings also the somatic components of dissociation may occur and
      influence brain, autonomic and neuroendocrine functions. At this time there are
      only few studies examining neuroendocrine response related to dissociative
      symptoms that suggest significant dysregulation of the hypothalamus-pituitary
      adrenal (HPA) axis. The aim of the present study is to perform examination of HPA
      axis functioning indexed by basal cortisol and prolactin and test their
      relationship to psychic and somatoform dissociative symptoms. MATERIAL/METHODS:
      Basal cortisol and prolactin and psychic and somatoform dissociative symptoms
      were assessed in 40 consecutive inpatients with diagnosis of unipolar depression
      mean age 43.37 (SD=12.21). RESULTS: The results show that prolactin and cortisol
      as indices of HPA axis functioning manifest significant relationship to
      dissociative symptoms. Main results represent highly significant correlations
      obtained by simple regression between psychic dissociative symptoms (DES) and
      serum prolactin (R=0.55, p=0.00027), and between somatoform dissociation (SDQ-20)
      and serum cortisol (R=-0.38, p=0.015). CONCLUSIONS: These results indicate
      relationship between HPA-axis reactivity and dissociative symptoms in unipolar
      depressive patients that could reflect passive coping behavior and disengagement.

PMID- 18830189
TI  - Nystagmus induced by bone (mastoid) vibration in otosclerosis: a new perspective
      in the study of vestibular function in otosclerosis.
AB  - BACKGROUND: The aim was to explore vestibular responses to bone vibration-induced
      nystagmus (BVIN) during bed-side examination in patients with otosclerosis and
      conductive hearing loss. It is assumed that vibration of the mastoid (at 100 Hz)
      stimulates all vestibular end organs (semicircular canals and otolith
      structures). Previous studies described oculomotor responses to vestibular
      activation by vibratory stimulus. Stimulation of individual semicircular canals
      produces eye movement in the plane of the stimulated canal. Vibratory stimulation
      of otolith structures (utricular macula) produces changes in ocular torsional
      position. Otosclerosis is responsible for conductive hearing loss and symptoms
      such as dizziness and vertigo. Diagnosis is usually by a combination of family
      medical history, conductive hearing loss pattern, absence of air-VEMP, and CT
      scan of the temporal bone. MATERIAL/METHODS: Eye movements of patients diagnosed
      with otosclerosis and conductive hearing loss were recorded in complete darkness.
      These oculomotor responses to long-lasting unilateral vibratory stimulation
      applied to the mastoid surface were evaluated and the patterns of vertical,
      torsional, and horizontal eye velocity and eye position were measured by three
      dimensional computerized infrared video oculography. RESULTS: Mastoid vibration
      evoked responses in all cases, mostly demonstrating excitation of the affected
      side. In all cases, three-dimensional infrared video oculography showed mostly
      horizontal nystagmus directed with the slow phase to the healthy side.
      CONCLUSIONS: Three-dimensional analysis of BVIN in patients with otosclerosis and
      conductive hearing loss may be appropriate in evaluating the vestibular function
      and altered immittance related with this clinical entity. This promises to be an
      interesting new field of research.

PMID- 18830190
TI  - Clinical and epidemiological features of upper-extremity infections caused by
      Staphylococcus aureus carrying the PVL gene: a four-year study in Greece.
AB  - BACKGROUND: All Staphylococcus aureus isolated during 2003-2006 at a university
      hospital in Thessalia, central Greece, from ulcerative upper-extremity infections
      were tested for the presence of PVL gene and for possible clonal relationship to
      validate the role of PVL toxin in the clinical features of these infections and
      also to establish preventive measures towards limiting the spread of such strains
      among close contacts. MATERIAL/METHODS: Of 305 bacterial cultures obtained from
      consecutive patients suffering from purulent musculoskeletal infections of an
      upper extremity, 207 revealed the presence of S. aureus (81 methicillin-resistant
      and 126 methicillin-sensitive). Seventy of the 207 cultures were found to be
      positive for the PVL gene. RESULTS: The PVL gene was detected in 12.1% (2003),
      46.7% (2004), 34% (2005), and 53% (2006) of upper-extremity staphylococcal
      infections, indicating a statistically significant increase between 2003 and 2004
      2006. However, there was a significant decrease in readmissions during 2005 and
      2006 and also in the number of relatives diagnosed with PVL-positive infections
      during the same period of time. The localization of these infections, their
      higher incidence during summer, and the transmission to family members indicated
      that contact was the means of spread of PVL-positive S. aureus. Most isolates
      belonged to the ST-80 clone, predominant in Europe. CONCLUSIONS: The emergence of
      new MRSA and also MSSA clones carrying the PVL gene and the decreases in
      readmissions and number of infected "close contacts" emphasizes the need for
      closer systematic surveillance and the implementation of preventive measures.

PMID- 18830191
TI  - EEG coherence characteristics at rest and during a three-level working memory
      task in normal aging and mild cognitive impairment.
AB  - BACKGROUND: The aim was to examine and compare the characteristics of intra- and
      inter-hemispheric EEG coherence in patients with mild cognitive impairment (MCI)
      and healthy controls at rest and during a working memory (WM) task having three
      levels. MATERIAL/METHODS: The subjects included 35 patients with MCI according to
      the DSM-IV criteria (mean age: 62.3+/-6.5 years) and 34 healthy controls (mean
      age: 57.4+/-4.0) selected from the community. All the subjects performed a simple
      calculation and recall task of WM with three levels of (WM1-3) while their EEG
      signal was recording. Inter- and intra-hemispheric EEG coherence was analyzed
      during the WM loads. RESULTS: Intra- and inter-hemispheric coherence during the
      WM task showed a "drop-to-rise" tendency compared with that at-rest condition.
      There was significantly higher coherence in MCI patients than in controls during
      the WM task. Intra-hemispheric ortical connectivity diminished while inter
      hemispheric connectivity dominated in the MCI patients during WM with increasing
      task difficulty. CONCLUSIONS: MCI patients and normal controls may have
      differences in cortical connection and MCI patients have a cortical connection
      disturbance during WM tasks. With increasing task difficulty the MCI patients
      mobilized more inter-hemispheric than intra-hemispheric cognitive resources.

PMID- 18830192
TI  - Effects of acute magnesium loading on pulmonary function of stable COPD patients.
AB  - BACKGROUND: Magnesium (Mg) use has the potential to promote bronchodilatation and
      to improve lung function in obstructive diseases. IV administration of Mg during
      exacerbations of chronic obstructive pulmonary disease (COPD) has led to improved
      peak flow. This study aimed to investigate the effects of acute IV Mg loading on
      respiratory parameters of stable COPD patients. MATERIAL/METHODS: This was a
      randomized, double-blind, placebo-controlled crossover study. Twenty-two male
      COPD patients (64+/-6 years old, FEV1: 49+/-20%) received an IV infusion of 2 g
      of magnesium sulfate or placebo on two distinct occasions. Spirometry and mouth
      maximal respiratory pressures were obtained before and 45 minutes after the
      infusions. RESULTS: Mg use led to significant changes in functional respiratory
      capacity (-0.48 l, 95%CI: -0.96, -0.01), inspiratory capacity (0.21 l, 95%CI:
      0.04, 0.37), maximal inspiratory pressure (10 cmH2O, 95%CI: 1.6, 18.4), and
      maximal expiratory capacity (10.7 cmH2O, 95%CI: 0.20, 21.2). The treatment was
      also associated with a marginally significant decrease in residual volume (-0.47
      L, 95%CI: -0.96, 0.02, p=0.06). CONCLUSIONS: Acute IV Mg loading in stable COPD
      patients was associated with a reduction in lung hyperinflation and improvement
      of respiratory muscle strength. The clinical potential for chronic magnesium
      supplementation in COPD deserves further investigation.

PMID- 18830193
TI  - Immunohistochemical study of decorin expression in polyps and carcinomas of the
      colon.
AB  - BACKGROUND: Recent studies showed that a small leucine-rich proteoglycan,
      decorin, may suppress tumor progression as a natural anticancer agent negatively
      controlling cellular growth. It was hypothesized that physiological expression of
      decorin may be associated with cellular senescence of the colorectal mucosa and
      that its down-regulation, promoting an increase in cellular proliferation, could
      participate in the progression of adenoma to adenocarcinoma. Therefore the
      expression of decorin in hyperplastic and neoplastic polyps of the colorectum was
      examined and compared with normal colonic mucosa and colon cancer tissues.
      MATERIAL/METHODS: Tissue samples were obtained from 41 patients with different
      types of colonic polyps (6 hyperplastic adenomas, 34 neoplastic adenomas, and 1
      adenomatous polyp with focal carcinoma) and 12 patients with colon cancer. Seven
      samples of normal colon tissue were used as controls. Paraffin-embedded samples
      were used for immunohistochemical study. RESULTS: Normal and hyperplastic tissues
      and the majority of tubular adenomas showed strong expression of decorin in the
      stroma. Adenomas with a villous component showed moderate and very low decorin
      immunoreactivity. The decrease in decorin reactivity in tubulo-villous adenomas
      was significant as compared with other polyps and controls. Weak decorin
      immunoreactivity in stroma adjacent to clusters of cancerous cells was also found
      in most cases of common types of adenocarcinoma, but not in adenocarcinoma
      mucinosum. CONCLUSIONS: The expression of decorin may be involved in the
      differentiation of colonic polyps and reduced expression of decorin may abrogate
      the defensive potential of stromal tissue and promote the development of common
      types of colon carcinoma.

PMID- 18830194
TI  - Combined impact of matrix metalloproteinase-3 and paraoxonase 1 55/192 gene
      variants on coronary artery disease in Turkish patients.
AB  - BACKGROUND: We investigated the association of matrix metalloproteinase-3 (MMP-3)
      and paraoxonase 1 (PON1) 55/192 polymorphisms with coronary artery disease (CAD)
      and the number of diseased vessels in patients with CAD. MATERIAL/METHODS: One
      hundred thirty-nine CAD patients and 119 healthy control subjects were included
      in the study. Genotypes for PON1 55/192 and MMP-3 5A/6A polymorphisms were
      determined by restriction fragment length polymorphism. RESULTS: Although
      distributions of the RR genotype of PON1 192 and the 5A5A genotype of MMP-3 were
      more frequent in patients, frequencies of the QQ genotype of PON1 192, the MM
      genotype of PON1 55, and the 6A6A genotype of MMP-3 were significantly lower in
      patients compared with healthy control subjects. The combined genotypes of RR/LL
      and/or 5A5A are increased the risk of CAD when compared with subjects who possess
      neither the MMP-3 5A5A nor the PON1 RR/LL genotype. While the MMP-3 5A/6A genetic
      variants were not associated with the number of diseased vessels, PON1 55/192
      variants were associated with the number of diseased vessels. CONCLUSIONS: The
      combined PON1 55/192 and MMP-3 5A/6A genetic variants are associated with CAD;
      PON1 seems to be connected with the number of diseased vessels, and hypertension
      and hyperlipidemia are related with PON1 192 and MMP-3 in CAD patients.

PMID- 18830195
TI  - A systematic study of a neutral meal suitable for subjects undergoing 13CO2
      breath tests.
AB  - BACKGROUND: Some 13CO2 breath tests require prolonged breath sampling. The study
      aimed to validate a meal which could be served to subjects without interference
      with the measured breath 13CO2 profile. MATERIAL/METHODS: Eight healthy
      volunteers were examined on three separate days. On two occasions they took
      equicaloric meals of 320 kcal composed of foodstuffs known to be poor in 13CO:
      cooked rice (R) or a wheat bread sandwich with butter and ham (S). On the control
      day they fasted. Samples of expiratory air were taken every 15 min for 6 hours.
      The 13CO2 concentration in the samples was measured by isotope ratio mass
      spectrometry. Statistical analysis involved repeated measures analysis of
      variance (RANOVA). RESULTS: The intra-subject variability of breath 13CO2
      concentration was remarkably low on the three study days, as reflected by mean
      coefficients of variation (CV) of 0.90+/-0.32%, 0.79+/-0.19%, and 0.80+/-0.34%
      for the control, meal S, and meal R days, respectively (RANOVA: F2;14=0.296,
      p=0.75). RANOVA indicated a strong effect of a meal on inter-subject variability
      of breath 13CO2 concentration (F2;46=390.62 p<0.000001). Post hoc comparisons
      revealed a mean CV of 1.64+/-0.37% on the control day, 3.62+/-0.18% after
      ingestion of S, and 3.81+/-0.24% after meal R (both p=0.000128 vs. the control).
      Nevertheless, with neither test meal did RANOVA disclose at any time a
      statistically significant deviation in breath 13CO2 concentration from the basal
      fasted value. CONCLUSIONS: Both the test meals fulfilled the requirement of
      neutrality as concerns a null effect on the breath 13CO2 profile.

PMID- 18830196
TI  - Spontaneous rib fractures in a black woman with familial hypocalciuric
      hypercalcemia.
AB  - BACKGROUND: Familial hypocalciuric hypercalcemia (FHH) is a rare but important
      consideration in the differential diagnosis of hypercalcemia. FHH results from an
      autosomal dominantly inherited inactivating mutation of the calcium sensing
      receptor (CaSR) gene and is typically associated with a benign clinical course
      and normal bone mineral density. CASE REPORT: We describe the unusual case of a
      57-year old African American woman with spontaneous rib fractures who was found
      to have FHH due to a novel set of polymorphisms of the CaSR gene. She also had
      hypertension, esophageal reflux disease treated with proton pump inhibitors,
      osteopenia by DEXA scanning, and a prior left ankle fracture in the absence of
      significant trauma. There was no suggestive family history and her only sibling
      had a normal serum calcium. The patient was evaluated extensively for potential
      causes of osteoporotic fractures. CONCLUSIONS: It is imperative to screen for FHH
      using 24-hour urinary calcium and creatinine excretion in subjects with
      hypercalcemia irrespective of ethnicity and a history of non-traumatic rib
      fractures. This approach may prevent unnecessary neck exploration for
      parathyroidectomy which is unwarranted in FHH.

PMID- 18830197
TI  - Double-balloon endoscopy for treatment of long-term abdominal discomfort due to
      small bowel penetration by an eel bone.
AB  - BACKGROUND: Penetration of the GI tract by a fish bone was treated by laparotomy.
      DBE is a useful procedure for removal of a foreign body from the small bowel.
      CASE REPORT: A 33-year-old male presented with bothersome postprandial fullness.
      He was diagnosed previously with functional dyspepsia, and had been treated with
      medication for 8 months with no success. During antegrade DBE, which was
      performed to rule out of small intestinal abnormalities, an eel bone found stuck
      in the jejunum was grasped with forceps and pulled out. Following removal of the
      bone, the patient's postprandial fullness ameliorated dramatically. CONCLUSIONS:
      This is the first report of DBE-based diagnosis and treatment of a small bowel
      penetration by a fish bone.

PMID- 18830198
TI  - Rehabilitation of an artist after right-hemisphere stroke.
AB  - BACKGROUND: Traditionally, in both medicine and neuropsychology, symptoms are
      defined as significant deviations in a given parameter from a "physiological"
      norm largely based on statistical studies of large populations. Thus the goal of
      rehabilitation is to bring the patient's performance within the bounds of
      acceptable variation from the norm, and this is what defines a good outcome.
      Although this model seems reasonable for "average" patients, in the case of
      "exceptional" patients an "average" outcome may not be acceptable. CASE REPORT:
      The present study describes the symptoms and successful rehabilitation of a
      prominent Polish artist, who was referred for rehabilitation after a right
      hemisphere stroke, and whose chief subjective complaint was the loss of artistic
      vision. The patient (female, ambidextrous) suffered an RH stroke at the age of
      61. In traditional rehabilitation many symptoms resolved and others were well
      compensated, but the patient continued to complain that she had a "hole" in her
      brain and could not paint. A special program of rehabilitation was designed for
      her, based on art therapy, but including many unique elements, using a
      microgenetic, "bottom-up" approach to energize creativity and bypass obstacles.
      Ultimately the patient was able to resume her artistic career, thanks to the
      heuristic, holistic approach to therapy. CONCLUSIONS: The case described here
      raises a number of theoretical questions about art, imagination, and creativity
      in the brain, and the goals of rehabilitation in the case of talented and gifted
      individuals.

PMID- 18830199
TI  - Characteristics of fulminant type 1 diabetes mellitus.
AB  - BACKGROUND: Fulminant type 1 diabetes is characterized by acute onset and rapid
      development of ketoacidosis. CASE REPORT: We present three cases of fulminant
      type 1 diabetes we experienced at our hospital. All three patients showed
      extremely high levels of plasma glucose, low HbA1c levels, positivity for urinary
      ketone bodies, ketoacidosis, and low C-peptide excretion. Flu-like symptoms were
      noted a few days before hospitalization, and increases in the WBC and CRP levels
      were observed. Interestingly, case 1 was negative for anti-GAD antibody at the
      time of hospitalization but became positive 22 days later. Moreover, this patient
      reverted to being negative for anti-GAD antibody 93 days later. Cases 1 and 3
      were positive for HLA-DR4 and HLA-DR9, and Case 2 was positive for HLA-DR4. All
      three individuals had flu-like symptoms and showed inflammatory markers in the
      blood. CONCLUSIONS: Although autoimmune abnormalities are not usually linked with
      fulminant type 1 diabetes, the conclusion drawn from the present study is that
      patients with this disease should be monitored on several different occasions for
      autoimmune antibodies.

PMID- 18830200
TI  - Personal impact factor: the need for speed.

PMID- 18830201
TI  - Onset of the symptoms in Alzheimer's disease. Comment to: Behavioral and
      psychological symptoms in the preclinical stage of Alzheimer's disease. Leszek
      Bidzan, Maria Pachalska, Bozena Grochmal-Bach, Mariola Bidzan, Anna Cieslukowska,
      Anna Pufal. Med Sci Monit, 2008; 14(9): CR473-79.

PMID- 18830203
TI  - Predictive value of color Doppler imaging in an evaluation of retrobulbar blood
      flow perturbation in young type-1 diabetic patients with regard to dyslipidemia.
AB  - BACKGROUND: The aim was to examine blood flow velocity and vascular resistance in
      retrobulbar arteries in young type-1 diabetes (DM-1) patients. Statistical
      relationships between blood flow parameters and serum lipid levels (TCH, HDL,
      LDL, TG, ApoB) were also determined. MATERIAL/METHODS: Fifty-two eyes with
      diabetic angiopathy were examined (average age: 18.54 years). Color Doppler
      imaging (CDI) was performed in the ophthalmic (OA), central retinal (CRA), and
      temporal posterior ciliary (TPCA) arteries. The parameters PSV, EDV, MV, PI, and
      RI were compared with those of a control group (46 eyes). The Student's t,
      Shapiro-Wilk, and Mann-Whitney U statistical tests were used (p< or =0.01 and p<
      or =0.05 were considered significant). RESULTS: Significant decreases in PSV, MV,
      PI, and RI in the OA, CRA, and TPCA and negative correlations between TCH, LDL,
      and ApoB and decreased PI and RI in the OA as well as positive correlations
      between these parameters and EDV in the OA were found. Increased ApoB correlated
      with decreased PI and RI in the TPCA. There were no significant relationships
      between TG and HDL and the blood flow parameters. Elevated levels of HbA1c and
      dyslipidemia were confirmed. CONCLUSIONS: CDI is an effective method for
      detecting retinochoroidal circulation disorders in the early stage of diabetic
      angiopathy. The alterations in retrobulbar blood flow were characterized by
      significant decreases in PSV, MV, and RI in the CRA and PSV, MV, PI, and RI in
      the TPCA. Dysregulation of TCH, LDL, and ApoB was associated with vascular
      resistance fluctuation, mainly in the OA.

PMID- 18830204
TI  - Safety and tolerability of 600 mg clopidogrel bolus in patients with acute
      ischemic stroke: preliminary experience.
AB  - BACKGROUND: There is a high risk of recurrence within the first 72 hours of
      ischemic stroke. Without bolus, the peak effect of clopidogrel may be delayed for
      72 hours. A bolus may shorten this time but its safety in acute ischemic stroke
      is unknown. MATERIAL/METHODS: All patients with acute ischemic stroke or
      transient ischemic attack within a 10 month period were administered 600 mg
      clopidogrel bolus if they were already taking aspirin regularly, or had aspirin
      allergy or intolerance. Demographic data, duration to initiation of therapy,
      National Institute of Health Stroke Scale score (NIHSSS) at baseline and at 24
      hours were collected. Brain imaging studies were reviewed for hemorrhagic
      transformation. Wilcoxin rank sum test was used for comparison of NIHSSS over
      time. RESULTS: A total of 20 patients (mean age 66+/-14, men n=8) were loaded
      with clopidogrel because of aspirin failure (n=16), aspirin allergy (n=1),
      aspirin intolerance secondary to gastritis (n=2) or stent placement in the
      setting of acute stroke (n=1). Median time interval between clopidogrel bolus and
      symptom onset was 25 hours. The median NIHSSS at 24 hours (1, range 0-15) was
      significantly (p<0.01) lower than the NIHSSS at baseline (3, range 0-24).
      Neurological deterioration (NIHSSS increase > or =4 points) or hemorrhagic
      transformation was not seen in any patient. CONCLUSIONS: A 600 mg clopidogrel
      bolus prior to initiating regular dose clopidogrel in the setting of acute
      ischemic stroke was safe. The potential for risk reduction in early recurrent
      stroke needs to be studied in future studies.

PMID- 18830205
TI  - Clinical case reports and case series research in evaluating surgery. Part II.
      The content and form: uses of single clinical case reports and case series
      research in surgical specialties.
AB  - Single clinical case and case series reports have long been an integral part of
      medicine and surgery. Despite this, due to their vague objectives and questions
      to answer, unstructured presentations and absent, exaggerated and/or
      unsubstantiated conclusions and recommendations, they are sometimes perceived as
      a lighter piece of evidence in modern surgical understanding and decision-making.
      Their value may, in fact, be in their contribution to theory, inference, or both.
      Today, modern case reporting is a balanced mixture of traditional patient
      centered reporting methodology, a quantitative approach to ("scientific")
      inference and growing experience from qualitative research and evaluation
      methodology in general policies, programs, politics, arts, humanities, business,
      economics, and the military. Integration of such experiences is possible and even
      desirable in modern clinical case(s) reporting. Both strengths and weaknesses of
      case(s) reporting are based on the structure and content of case(s) reports in
      terms of the clarity of their leading questions and objectives, structured
      presentation in form and valid argument building blocks founded on the best
      evidence available leading to their realistic conclusions and claims. Readers
      must assess their real value in general and in the context of their own decisions
      in research and practice with patients under their care and in decision-making.
      Most discussion about single clinical case reports and case series research
      revolves around their relevance to some degree of proof of cause-effect
      relationships. The relevance of case reports and case series research goes well
      beyond this point. Recommendations for both surgical and other case presenters
      and their interlocutors and readers are offered for consideration.

PMID- 18830206
TI  - Transplantation of human umbilical cord blood cells for the repair of myocardial
      infarction.
AB  - Cell therapy for myocardial disease is a rapidly evolving medical field. A vast
      and growing body of evidence indicates that cell-based strategies have promising
      therapeutic potential. Recent clinical and pre-clinical studies demonstrate a
      varying degree of improvement in cardiac function using different sources of
      adult stem cell types such as bone marrow-derived progenitor cells and skeletal
      myoblasts. However, the currently available regimens for cell transplantation
      into the infarcted myocardium have limitations from practical points of view, in
      particular the logistics in harvesting donor cells. Accordingly, there is an
      urgent need for a new source of adult stem cells. Human umbilical cord blood
      (HUCB) is a good candidate and appears to have several key advantages. HUCB is a
      viable and practical source of progenitor cells. Compared to bone marrow, HUCB
      contains a higher number of immature stem/progenitor cells. The aim of our review
      is to provide an update on the preclinical experiments with emphasis on the
      possible mechanisms underlying the therapeutic benefits of HUCB cell
      transplantation for myocardial infarction.

PMID- 18830207
TI  - Limited place for plasma monitoring of new antiepileptic drugs in clinical
      practice.
AB  - Therapeutic drug monitoring (TDM) has been recognized as a useful guide in the
      clinical management of patients with epilepsy, in particular those on therapy
      with traditional antiepileptic drugs (AEDs). The demonstration of significant
      drug interactions and the introduction of the concept "therapeutic range" have
      also contributed to the view that monotherapy should be considered the "gold
      standard" in the treatment of epilepsy. Ten new AEDs have been approved and
      released to the market in the last fifteen years. The most obvious consequence
      has been an increased number of patients on polytherapy. In general, newer AEDs
      have better and more predictable pharmacokinetics than older AEDs and usually
      show lower risk of interactions leading to toxicity as well as large therapeutic
      indexes. This pragmatic review focuses on practical suggestions about the
      potential clinical usefulness of TDM of newer AEDs in relation to their mechanism
      of action and pharmacokinetic characteristics and in response to patient-specific
      problems. Overall, the usefulness of TDM of newer AEDs seems to be limited and
      its indiscriminate use is not justified. However, in selected cases or in
      response to a specific clinical question, a wise use of TDM of some new AEDs
      could represent a useful tool in the management of epileptic patients. Exceptions
      are thus represented by special conditions such as renal failure, dialysis,
      ascertainment of non-compliance, and pregnancy. For some new AEDs, TDM could be
      selectively and properly used in response to a single patient-specific
      pharmacokinetic or pharmacodynamic issue.

PMID- 18830208
TI  - Biological properties of interleukin 2 and its role in pathogenesis of selected
      diseases--a review.
AB  - Interleukin 2 (IL-2), or T-cell growth factor (TCGF), represents the first
      identified, fully-characterized, purified human interleukin. It is produced
      mainly by T helper (CD4+) lymphocytes, stimulates cell-mediated immune responses,
      controls growth and differentiation of B lymphocytes, and intensifies
      proliferation and activity of all cytotoxic cell clones. IL-2 is a growth factor
      in vitro and a mediator of self-tolerance in vivo, and therefore interests tumor
      immunotherapy investigators. The role of IL-2 in the cell cycle of neoplastic
      cells remains unclear. IL-2 inhibits growth of certain human tumor cells while
      proliferation of other cells remains intact or is even stimulated. Decreased IL-2
      production is often observed in the more advanced clinical stages of human
      tumors, which provides rational for inclusion of recombinant IL-2 in the
      immunotherapy for some tumors. On the other hand, tumor cells themselves may
      produce IL-2 and promote tumor growth. This article summarizes the current
      physiological role of IL-2 and its role in the pathogenesis of select human
      diseases. Many papers (including reviews) pertain to the IL-2R receptor. The
      soluble form of the alpha subunit of the IL-2 receptor (sIL-2Ralpha) is elevated
      in most proliferative disturbances of the hematopoietic system and in many solid
      tumors. Special reference to the most important discoveries and our own
      experience in intracellular detection of IL-2 and IL-2Ralpha are included. IL-2
      properties, cellular sources, and targets, including data on its expression in
      pathological conditions, continue to be supplemented. Attempts to treat tumors
      are also discussed, using modified varieties of therapy that use IL-2 itself
      and/or its receptor.

PMID- 18830209
TI  - Racial/ethnic disparities in self-rated health status among adults with and
      without disabilities--United States, 2004-2006.
AB  - Self-rated health status has been found to be an independent predictor of
      morbidity and mortality, and racial/ethnic disparities in self-rated health
      status persist among the U.S. adult population. Black and Hispanic adults are
      more likely to report their general health status as fair or poor compared with
      white adults. In addition, the prevalence of disability has been shown to be
      higher among blacks and American Indians/Alaska Natives (AI/ANs) (3). To estimate
      differences in self-rated health status by race/ethnicity and disability, CDC
      analyzed data from the 2004-2006 Behavioral Risk Factor Surveillance System
      (BRFSS) surveys. This report summarizes the results of that analysis, which
      indicated that the prevalence of disability among U.S. adults ranged from 11.6%
      among Asians to 29.9% among AI/ANs. Within each racial/ethnic population, adults
      with a disability were more likely to report fair or poor health than adults
      without a disability, with differences ranging from 16.8 percentage points among
      Asians to 37.9 percentage points among AI/ANs. Efforts to reduce racial/ethnic
      health disparities should explicitly include strategies to improve the health and
      well being of persons with disabilities within each racial/ethnic population.

PMID- 18830210
TI  - HIV prevalence estimates--United States, 2006.
AB  - Accurate and timely data on the number of persons in the United States living
      with human immunodeficiency virus (HIV) infection (HIV prevalence) are needed to
      guide planning for disease prevention, program evaluation, and resource
      allocation. However, overall HIV prevalence cannot be measured directly because a
      proportion of persons infected with HIV have neither been diagnosed nor reported
      to local surveillance programs. In addition, national HIV prevalence data are
      incomplete because local reporting systems for confidential, name-based HIV
      reporting have been fully implemented only since April 2008. With the advent of
      highly active antiretroviral therapies that delay the progression of HIV to
      acquired immunodeficiency syndrome (AIDS), and of AIDS to death, and changes in
      the AIDS case definition to include an immunologic diagnosis, earlier back
      calculation methods from the 1990s for estimating HIV prevalence based on the
      number of reported AIDS cases are no longer reliable. With 80% of states
      reporting name-based HIV diagnoses as of January 2006, an extended back
      calculation method now can be used to estimate HIV prevalence more accurately.
      Based on this method, CDC now estimates that 1.1 million adults and adolescents
      (prevalence rate: 447.8 per 100,000 population) were living with diagnosed or
      undiagnosed HIV infection in the United States at the end of 2006. The majority
      of those living with HIV were nonwhite (65.4%), and nearly half (48.1%) were men
      who have sex with men (MSM). The HIV prevalence rates for blacks (1,715.1 per
      100,000) and Hispanics (585.3 per 100,000) were, respectively, 7.6 and 2.6 times
      the rate for whites (224.3 per 100,000).

PMID- 18830211
TI  - Rabies in a dog imported from Iraq--New Jersey, June 2008.
AB  - Rabies vaccination and stray dog control have led to successful control of canine
      rabies in the United States. The number of rabid dogs reported decreased from
      approximately 5,000 in 1950 to 79 in 2006, when the canine rabies virus variant
      associated with dog-to-dog rabies transmission was declared eliminated in the
      United States. On June 18, 2008, a mixed-breed dog, recently shipped from Iraq
      into the United States, was confirmed to have rabies by the Public Health and
      Environmental Laboratories of the New Jersey Department of Health and Senior
      Services. A total of 24 additional animals in the shipment, all potentially
      exposed to the rabid dog, were distributed to 16 states. This report summarizes
      the epidemiologic investigation by the New Jersey Department of Health and Senior
      Services, Bergen County Department of Health, and CDC, and the ensuing public
      health response. These findings underscore the need for vigilance regarding
      rabies (and other zoonotic diseases) during animal importation to prevent the
      possible reintroduction and sustained transmission of canine rabies in U.S. dog
      populations.

PMID- 18830212
TI  - Licensure of a diphtheria and tetanus toxoids and acellular pertussis adsorbed
      and inactivated poliovirus vaccine and guidance for use as a booster dose.
AB  - On June 24, 2008, the Food and Drug Administration licensed a combined diphtheria
      and tetanus toxoids and acellular pertussis adsorbed (DTaP) and inactivated
      poliovirus (IPV) vaccine, DTaP-IPV (Kinrix, GlaxoSmithKline Biologicals,
      Rixensart, Belgium). Kinrix is licensed for use as the fifth dose of the DTaP
      vaccine series and the fourth dose of the IPV series in children aged 4-6 years
      whose previous DTaP vaccine doses were DTaP (Infanrix, GlaxoSmithKline) and/or
      DTaP-Hepatitis B-IPV (Pediarix, GlaxoSmithKline) for the first 3 doses and DTaP
      (Infanrix) for the fourth dose. DTaP-IPV administered to children aged 4-6 years
      would reduce by one the number of injections needed to complete DTaP and IPV
      immunization. This report summarizes the indications for Kinrix and provides
      guidance from the Advisory Committee on Immunization Practices (ACIP) for its
      use.

PMID- 18830213
TI  - Licensure of a diphtheria and tetanus toxoids and acellular pertussis adsorbed,
      inactivated poliovirus, and haemophilus B conjugate vaccine and guidance for use
      in infants and children.
AB  - On June 20, 2008 the Food and Drug Administration (FDA) licensed a combined
      diphtheria and tetanus toxoids and acellular pertussis adsorbed (DTaP),
      inactivated poliovirus vaccine (IPV), and Haemophilus influenzae type b conjugate
      (tetanus toxoid [TT] conjugate) vaccine, DTaP-IPV/Hib (Pentacel, Sanofi Pasteur,
      Swiftwater, Pennsylvania), for use as a four-dose series in infants and children
      at ages 2, 4, 6, and 15-18 months. This report summarizes the indications for
      Pentacel and provides guidance from the Advisory Committee on Immunization
      Practices (ACIP) for its use.

PMID- 18830214
TI  - Surveillance for Lyme disease--United States, 1992-2006.
AB  - PROBLEM/CONDITION: Lyme disease is a multisystem disease that occurs in North
      America, Europe, and Asia. In the United States, the etiologic agent is Borrelia
      burgdorferi sensu stricto, a spirochete transmitted to humans by infected Ixodes
      scapularis and I. pacificus ticks. The majority of patients with Lyme disease
      develop a characteristic rash, erythema migrans (EM), accompanied by symptoms of
      fever, malaise, fatigue, headache, myalgia, or arthralgia. Other manifestations
      of infection can include arthritis, carditis, and neurologic deficits. Lyme
      disease can be treated successfully with standard antibiotic regimens. REPORTING
      PERIOD: 1992--2006. DESCRIPTION OF SYSTEM: U.S. health departments report cases
      of Lyme disease voluntarily to CDC as part of the National Notifiable Disease
      Surveillance System. Variables collected include patient age, sex, race, county
      and state of residence, date of illness onset, and reported signs and symptoms.
      RESULTS: During 1992--2006, a total of 248,074 cases of Lyme disease were
      reported to CDC by health departments in the 50 states, the District of Columbia,
      and U.S. territories; the annual count increased 101%, from 9,908 cases in 1992
      to 19,931 cases in 2006. During this 15-year period, 93% of cases were reported
      from 10 states (Connecticut, Delaware, Massachusetts, Maryland, Minnesota, New
      Jersey, New York, Pennsylvania, Rhode Island, and Wisconsin). Incidence was
      highest among children aged 5--14 years, and 53% of all reported cases occurred
      among males. More than 65% of patients with EM had illness onset in June and
      July, compared with 37% of patients with arthritis. INTERPRETATION: Lyme disease
      is the most commonly reported vectorborne illness in the United States. The
      geographic distribution of cases is highly focused, with the majority of reported
      cases occurring in the northeastern and north-central states. During 1992--2006,
      the number of reported cases more than doubled. A disproportionate increasing
      trend was observed in children and in young males compared with other demographic
      groups. PUBLIC HEALTH ACTION: The results presented in this report underscore the
      continued emergence of Lyme disease and the need for tick avoidance and early
      treatment interventions. Public health practitioners can use the data presented
      in this report to target prevention campaigns to populations with increasing
      incidence (i.e., children and young males).

PMID- 18830215
TI  - Standardizing data.

PMID- 18830217
TI  - Pores galore for the Golgi.

PMID- 18830218
TI  - One hit, two outcomes for VHL-mediated tumorigenesis.

PMID- 18830219
TI  - Stressed out? Make some modifications!

PMID- 18830220
TI  - Dynein branches out.
AB  - Individual neurons form specific elaborate dendritic structures that receive
      presynaptic information. The pattern of dendritic branching is regulated by the
      microtubule-associated motor protein dynein, which is responsible for the
      transport of essential endosomes and other organelles into the dendrites.

PMID- 18830222
TI  - Bullies.

PMID- 18830223
TI  - Viral vigilance. New surveillance strategies and methods help to identify
      dangerous pathogens earlier: a prerequisite for efficient countermeasures.

PMID- 18830224
TI  - Not a welcoming place. A new study sheds light on the situation of women
      scientists and engineers in the private sector.

PMID- 18830225
TI  - The pharmacokinetics and bioavailability of prochlorperazine delivered as a
      thermally generated aerosol in a single breath to volunteers.
AB  - A thermally generated aerosol (TGA) system can effect reliable delivery of
      excipient-free drug to alveoli, resulting in rapid systemic drug absorption. We
      developed a pharmacokinetic model of prochlorperazine, administered by inhalation
      and as a rapid intravenous infusion, and we determined absolute TGA
      bioavailability in eight healthy volunteers in this institutional review board
      approved, two-period crossover study. After the drug was administered as either a
      5-s intravenous infusion or a TGA single-breath inhalation, blood was collected
      at various times for up to 24 h. Plasma prochlorperazine concentrations were
      measured using liquid chromatography-tandem mass spectrometry. Inhalation and
      rapid intravenous administration produced similar plasma prochlorperazine
      concentration profiles. Intravenous and inhalation pharmacokinetics were well
      characterized by a simultaneous two-compartment model with multiple absorption
      delays. Prochlorperazine pharmacokinetic parameters were similar to those
      reported for single intravenous doses. The geometric mean bioavailability after
      TGA delivery was 1.10. The administration of prochlorperazine by inhalation
      resulted in pharmacokinetics similar to that seen after intravenous
      administration, in terms of speed, extent, and consistency of absorption.

PMID- 18830226
TI  - Personalized therapeutics: HIV treatment in adolescents.

PMID- 18830227
TI  - PTCH1 duplication in a family with microcephaly and mild developmental delay.
AB  - With the exception of the X chromosome, genomic deletions appear to be more
      prevalent than duplications. Because of a lack of accurate diagnostic methods,
      submicroscopic duplications have been under-ascertained for a long period. The
      development of array CGH has enabled the detection of chromosomal
      microduplications with nearly the same sensitivity as deletions, leading to the
      discovery of previously unrecognized syndromes. Using a clinical targeted
      oligonucleotide array (CMA-V6.3 OLIGO), we identified an approximately 360-kb
      duplication in 9q22.32 in a 21-month-old boy with developmental delay, failure to
      thrive, and microcephaly. The same duplication was identified in the patient's
      mother who is also microcephalic and mildly delayed. We have sequenced the
      chromosomal breakpoints and determined the duplication as tandem in orientation
      and 363 599 bp in size. The duplicated segment harbors the entire PTCH1 gene.
      Deletions or loss-of-function mutations of PTCH1 result in basal cell nevus
      syndrome (Gorlin syndrome), whereas gain-of-function mutations were proposed to
      lead to holoprosencephaly 7. We propose that patients with microcephaly or
      holoprosencephaly of unknown origin should also be screened for PTCH1
      duplication.

PMID- 18830228
TI  - Misleading behavioural phenotype with adenylosuccinate lyase deficiency.
AB  - Adenylosuccinate lyase deficiency is a rare autosomal disorder of de novo purine
      synthesis, which results in the accumulation of succinylpurines in body fluids.
      Patients with adenylosuccinate lyase deficiency show a variable combination of
      mental retardation, epilepsy and autistic features and are usually discovered
      during screens for unexplained encephalopathy using the Bratton-Marshall assay
      that reveals the excretion of the succinylaminoimidazolecarboxamide riboside
      (SAICAr). Here, we report on two sisters aged 11 and 12 years presented with
      global developmental delay, motor apraxia, severe speech deficits, seizures and
      behavioural features, which combined excessive laughter, a very happy
      disposition, hyperactivity, a short attention span, the mouthing of objects,
      tantrums and stereotyped movements that gave a behavioural profile mimicking
      Angelman syndrome. Both patients had an increased succinyladenosine/SAICAr ratio
      of 1.6, and exhibited a novel homozygous missense mutation (c.674T>C;
      p.Met225Thr) in the exon 6 of the ADSL gene. We suggest that these clinical
      features might be a new presentation of adenylosuccinate lyase deficiency. On the
      basis of this observation, although adenylosuccinate lyase deficiency is a rare
      disorder, this diagnosis should be considered in patients with mental retardation
      and a behavioural profile suggestive of Angelman syndrome.

PMID- 18830229
TI  - Missense mutations to the TSC1 gene cause tuberous sclerosis complex.
AB  - Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterised
      by the development of hamartomas in a variety of organs and tissues. The disease
      is caused by mutations in either the TSC1 gene on chromosome 9q34 or the TSC2
      gene on chromosome 16p13.3. The TSC1 and TSC2 gene products, TSC1 and TSC2,
      interact to form a protein complex that inhibits signal transduction to the
      downstream effectors of the mammalian target of rapamycin (mTOR). Here we
      investigate the effects of putative TSC1 missense mutations identified in
      individuals with signs and/or symptoms of TSC on TSC1-TSC2 complex formation and
      mTOR signalling. We show that specific amino-acid substitutions close to the N
      terminal of TSC1 reduce steady-state levels of TSC1, resulting in the activation
      of mTOR signalling and leading to the symptoms of TSC.

PMID- 18830230
TI  - Wolf-Hirschhorn syndrome facial dysmorphic features in a patient with a terminal
      4p16.3 deletion telomeric to the WHSCR and WHSCR 2 regions.
AB  - We report on a patient with developmental delay and several facial
      characteristics reminiscent of Wolf-Hirschhorn syndrome, who carries a terminal
      4p16.3 deletion of minimally 1.691 Mb and maximally 1.698 Mb. This deletion
      contains the FGFRL1 gene, but does not include the WHSC1 gene. Given its
      expression pattern and its involvement in bone and cartilage formation during
      embryonic development, the FGFRL1 gene represents a plausible candidate gene for
      part of the facial characteristics of Wolf-Hirshhorn syndrome in 4p16.3 deletion
      patients.

PMID- 18830231
TI  - Identification of a prostate cancer susceptibility gene on chromosome 5p13q12
      associated with risk of both familial and sporadic disease.
AB  - Genetic heterogeneity is a difficulty frequently encountered in the search for
      genes conferring susceptibility to prostate cancer. To circumvent this issue, we
      selected a large prostate cancer pedigree for genome-wide linkage analysis from a
      population that is genetically homogeneous. Selected cases and first-degree
      relatives were genotyped with Affymetrix 10K SNP arrays, identifying a 14 Mb
      haplotype on chromosome 5 (5p13-q12) inherited identical-by-descent (IBD) by
      multiple cases. Microsatellite genotyping of additional deceased case samples
      confirmed that a total of eight cases inherited the common haplotype (P=0.0017).
      Re-sequencing of eight prioritised candidate genes in the region in six selected
      individuals identified 15 SNPs segregating with the IBD haplotype, located within
      the ITGA2 gene. Three of these polymorphisms were selected for genotyping in an
      independent Tasmanian data set comprising 127 cases with familial prostate
      cancer, 412 sporadic cases and 319 unaffected controls. Two were associated with
      prostate cancer risk: rs3212649 (OR=1.67 (1.07-2.6), P=0.0009) and rs1126643
      (OR=1.52 (1.01-2.28), P=0.0088). Significant association was observed in both
      familial and sporadic prostate cancer. Although the functional SNP remains to be
      identified, considerable circumstantial evidence, provided by in vivo and in
      vitro studies, supports a role for ITGA2 in tumour development.

PMID- 18830232
TI  - Mutational analysis of the ACVR1 gene in Italian patients affected with
      fibrodysplasia ossificans progressiva: confirmations and advancements.
AB  - Fibrodysplasia ossificans progressiva (FOP, MIM 135100) is a rare genetic
      disorder characterized by congenital great toe malformations and progressive
      heterotopic ossification transforming skeletal muscles and connective tissues to
      bone following a well-defined anatomic pattern of progression. Recently, FOP has
      been associated with a specific mutation of ACVR1, the gene coding for a bone
      morphogenetic protein type I receptor. The identification of ACVR1 as the
      causative gene for FOP now allows the genetic screening of FOP patients to
      identify the frequency of the identified recurrent ACVR1 mutation and to
      investigate genetic variability that may be associated with this severely
      debilitating disease. We report the screening for mutations in the ACVR1 gene
      carried out in a cohort of 17 Italian patients. Fifteen of these displayed the
      previously described c.617G>A mutation, leading to the R206H substitution in the
      GS domain of the ACVR1 receptor. In two patients, we found a novel mutation
      c.774G>C, leading to the R258S substitution in the kinase domain of the ACVR1
      receptor. In the three-dimensional model of protein structure, R258 maps in close
      proximity to the GS domain, a key regulator of ACVR1 activity, where R206 is
      located. The GS domain is known to bind the regulatory protein FKBP12 and to
      undergo multiple phosphorylation events that trigger a signaling cascade inside
      the cell. The novel amino-acid substitution is predicted to influence either the
      conformation/stability of the GS region or the binding affinity with FKBP12,
      resulting in a less stringent inhibitory control on the ACVR1 kinase activity.

PMID- 18830233
TI  - Mutations in mammalian tolloid-like 1 gene detected in adult patients with ASD.
AB  - Atrial septal defect (ASD) is an incomplete septation of atria in human heart
      causing circulatory problems. Its frequency is estimated at one per 10 000.
      Actions of numerous genes have been linked to heart development. However, no
      single gene defect causing ASD has yet been identified. Incomplete heart
      septation similar to ASD was reported in transgenic mice with both inactive
      alleles of gene encoding mammalian zinc metalloprotease a mammalian tolloid-like
      1 (tll1). Here, we have screened 19 ASD patients and 15 healthy age-matched
      individuals for mutations in TLL1 gene. All 22 exons were analyzed exon by exon
      for heteroduplex formation. Subsequently, DNA fragments forming heteroduplexes
      were sequenced. In four nonrelated patients, three missense mutations in coding
      sequence, and one single base change in the 5'UTR have been detected. Two
      mutations (Met182Leu, and Ala238Val) were detected in ASD patients with the same
      clinical phenotype. As the second mutation locates immediately upstream of the
      catalytic zinc-binding signature, it might change the enzyme substrate
      specificity. The third change, Leu627Val in the CUB3 domain, has been found in an
      ASD patient with interatrial septum aneurysm in addition to ASD. The CUB3 domain
      is important for substrate-specific recognition. In the remaining 15 patients as
      well as in 15 reference samples numerous base substitutions, deletions, and
      insertions have been detected, but no mutations changing the coding sequence have
      been found. Lack of mutations in relation to ASD of these patients could possibly
      be because of genetic heterogeneity of the syndrome.

PMID- 18830234
TI  - Dermal absorption of environmental contaminants from soil and sediment: a
      critical review.
AB  - Risk assessment of hazardous wastes sites may require characterization of the
      dermal availability of chemical contaminants in soil and/or sediment. Current
      U.S. Environmental Protection Agency guidance for assessment of dermal exposures
      to contaminants in water and soil was finalized in 2004 as a supplement (Part E)
      to the Risk Assessment Guidance for Superfund (RAGS). The soil protocol presented
      in RAGS Part E is less sophisticated than the water protocol and is supported by
      less empirical data. Investigations of dermal absorption of soil and sediment
      borne contaminants that have been conducted to date include in vitro and in vivo
      experiments using both human and surrogate skin. A review of that literature was
      conducted with attention to relevant criteria including consideration of layering
      effects, degree of chemical saturation of soil, appropriateness of particle size
      distribution employed, soil-chemical contact time, and continuity of soil-skin
      contact (in in vivo studies). Most studies published to date are deficient by
      virtue of execution or reporting on one or more of the selected criteria. In
      addition the lack of methodological standardization evident in the literature
      hinders systematic evaluation of results. Since additional experimental work is
      needed, general agreement on acceptable approaches would be useful.
      Recommendations for good practice are presented.

PMID- 18830235
TI  - Variability and predictors of changes in water use during pregnancy.
AB  - Disinfection by-products in tap water have been found in some studies to be
      associated with adverse pregnancy outcomes, but little is known about how water
      use and consumption might change during early pregnancy. Estimating water-related
      activities only at one time during pregnancy could easily lead to exposure
      misclassification. To evaluate changes in water use among pregnant women, we used
      data from a large epidemiologic study in which 1990 women were interviewed around
      9 and 20 weeks' gestation. The water variables that were examined included
      ingestion of cold and hot tap water as well as of bottled water, showering and
      bathing. Changes were detected between early and mid-pregnancy for ingested cold
      tap water and showering. Thirty-three percent of the subjects changed cold-water
      ingestion by > or =1.0 liters/day and 44% changed their time showering by > or
      =35 min per week during this period. Increases in cold tap water intake were
      associated with age >35 years, income < $40,000, and non-Hispanic white
      ethnicity. We also found that the proportion of the total variation due to within
      subject variability was 62% for hot tap water ingestion but only 35% for
      showering and approximately 50% for cold tap water, bottled water and bathing.
      Limited resources in epidemiologic studies often require a decision between
      collecting data for a large number of people or collecting multiple measurements
      for a smaller number of people. The results in this study will be useful to
      researchers who need to determine where to invest their effort when assessing
      water-related exposures and should help in evaluation of previously performed
      studies.

PMID- 18830236
TI  - Evidence why paroxetine dose escalation is not effective in major depressive
      disorder: a randomized controlled trial with assessment of serotonin transporter
      occupancy.
AB  - Dose escalation is often used in depressed patients who fail to respond to
      standard doses of selective serotonin reuptake inhibitors, but clinical efficacy
      is equivocal. We aimed to reassess the efficacy of paroxetine dose escalation and
      quantify whether paroxetine dose escalation increases occupancy of the serotonin
      transporter (SERT) more than placebo dose escalation in a randomized controlled
      trial. We recruited 107 nonpsychotic, unipolar depressed outpatients (18-70
      years; Hamilton Depression Rating Scale (HDRS(17)) >18) from primary care and
      psychiatric outpatient departments. After 6 weeks, open-label paroxetine 20 mg
      per day (T0), nonresponding patients (HDRS(17) decrease <50%; n=60) were
      randomized to double-blind paroxetine (30-50 mg per day as tolerable) or placebo
      dose escalation (paroxetine 20 mg per day+placebo). Patients were followed until
      6 weeks after randomization (T1). Forty-nine patients, drug free at study entry,
      underwent single-photon emission-computed tomography (SPECT) scanning before
      treatment and were scanned repeatedly at T0 and T1. Paroxetine serum
      concentrations and SERT occupancy were determined at T0 and T1 (n=32). We
      terminated the dose-escalation trial after an interim analysis. Thirty
      nonresponding patients were randomized to paroxetine (46.7+/-5.5 mg per day), 27
      to placebo dose escalation. Response rates were 10/30 (33.3%) and 10/27 (37.0%),
      respectively. Repeated measurement analyses showed no significant effect for
      treatment (p=0.88, exceeding a priori stopping rules for futility (p>0.5)).
      Overall dropout was higher for placebo (26.7%) than paroxetine (3.3%; p=0.03).
      Paroxetine dose escalation increased paroxetine serum concentrations (p<0.001).
      SPECT measurements (12 patients randomized to paroxetine (46.9+/-4.8 mg) and 14
      to placebo dose escalation) showed no significant increase of midbrain SERT
      occupancy (2.5+/-26.4%, paroxetine; 3.1+/-25.8% placebo; p=0.687) nor in
      diencephalon (p=0.529). Paroxetine dose escalation in depressed patients has no
      clinical benefit over placebo dose escalation. This is explained by the absence
      of significant increases of SERT occupancy by paroxetine dose escalation, despite
      increased paroxetine serum concentrations (ISRCTN44111488).

PMID- 18830238
TI  - Bridging bench and practice: translational research for schizophrenia and other
      psychotic disorders.
AB  - Translational research is urgently needed to turn basic scientific discoveries
      into widespread health gains and nowhere are these needs greater than in
      conditions such as schizophrenia and other psychotic disorders. In this article,
      we discuss one type of translational research--called T1--which is needed to take
      advantage of developments in the basic neurosciences and translate them into more
      efficacious diagnostic, preventive, and therapeutic interventions. However,
      ensuring that interventions from T1 research actually benefit patients will
      require a second form of translational research--called T2--to turn innovations
      into everyday clinical practice and health decision-making. Recent examples of T1
      and T2 research in schizophrenia and other psychotic disorders as well as
      strategies for better linking T1 and T2 research agendas are covered.

PMID- 18830237
TI  - Involvement of amygdala dopamine and nucleus accumbens NMDA receptors in ethanol
      seeking behavior in mice.
AB  - Although progress has been made identifying neural mechanisms underlying
      ethanol's primary reinforcing effects, few studies have examined the mechanisms
      mediating ethanol-induced conditioned effects. A recent lesion study suggests
      that expression of ethanol-conditioned behaviors depends upon an intact amygdala
      and nucleus accumbens core. However, specific mechanisms within these nuclei are
      unknown. In the present experiments, we used site-specific microinfusions of
      dopamine and NMDA receptor antagonists to examine the roles of accumbens and
      amygdala in the expression of ethanol conditioned place preference (CPP) in mice.
      In experiments 1 and 2, a D1/D2/D3 receptor antagonist (flupenthixol) was infused
      into accumbens or amygdala before testing, whereas experiment 3 used pretest
      infusions of an NMDA antagonist (AP-5) to examine the role of intra-accumbens
      NMDA receptors. Dopamine antagonism of accumbens was without effect, but intra
      amygdala infusions of flupenthixol blocked CPP expression. Moreover, this effect
      was dependent upon dopamine antagonism within the basolateral nucleus but not the
      central nucleus of the amygdala. Antagonism of NMDA receptors in accumbens also
      blocked CPP expression. The present findings suggest that expression of the
      ethanol-conditioned response depends upon amygdala dopamine and accumbens NMDA
      receptors. These are the first studies in any species to show a role for amygdala
      dopamine receptors and the first studies in mice to implicate accumbens NMDA
      receptors in ethanol-induced conditioned effects.

PMID- 18830239
TI  - Neurokinin1 antagonists potentiate antidepressant properties of serotonin
      reuptake inhibitors, yet blunt their anxiogenic actions: a neurochemical,
      electrophysiological, and behavioral characterization.
AB  - Though neurokinin(1) (NK(1)) receptor antagonists are active in experimental
      models of depression, clinical efficacy has proven disappointing. This encourages
      interest in association of NK(1) receptor blockade with inhibition of serotonin
      (5-HT) reuptake. The selective NK(1) antagonist, GR205171, dose-dependently
      enhanced citalopram-induced elevations of extracellular levels of 5-HT in frontal
      cortex, an action expressed stereospecifically vs its less active distomer,
      GR226206. Further, increases in 5-HT levels in dorsal hippocampus, basolateral
      amygdala, nucleus accumbens, and striatum were likewise potentiated, and GR205171
      similarly facilitated the influence of fluoxetine upon levels of 5-HT, as well as
      dopamine and noradrenaline. In parallel electrophysiological studies, the
      inhibitory influence of citalopram and fluoxetine upon raphe-localized
      serotonergic neurones was stereospecifically blunted by GR205171. Antidepressant
      actions of citalopram in a forced-swim test in mice were stereospecifically
      potentiated by GR205171, and it also enhanced attenuation by citalopram of stress
      related ultrasonic vocalizations in rats. Further, GR205171 and citalopram
      additively abrogated the advance in circadian rhythms provoked by exposure to
      light in hamsters. By contrast, GR205171 stereospecifically blocked anxiogenic
      actions of citalopram in social interaction procedures in rats and gerbils, and
      stereospecifically abolished facilitation of fear-induced foot tapping by
      fluoxetine in gerbils. By analogy to GR205171, a further NK(1) antagonist,
      RP67580, enhanced the influence of citalopram upon frontocortical levels of 5-HT
      and potentiated its actions in the forced swim test. In conclusion, NK(1)receptor
      blockade differentially modulates functional actions of SSRIs: antidepressant
      properties are reinforced, whereas anxiogenic effects are attenuated. Combined
      NK(1) receptor antagonism/5-HT reuptake inhibition may offer advantages in the
      management of depressed and anxious states.

PMID- 18830241
TI  - Response perseveration and ventral prefrontal sensitivity to reward and
      punishment in male problem gamblers and smokers.
AB  - Pathological gambling (PG) is associated with maladaptive perseverative behavior,
      but the underlying mechanism and neural circuitry is not completely clear. Here,
      the hypothesis was tested that PG is characterized by response perseveration and
      abnormalities in reward and/or punishment sensitivity in the ventral
      frontostriatal circuit. Executive functioning was assessed to verify if these
      effects are independent of the dorsal frontostriatal circuit. A group of smokers
      was also included to examine whether impairments in PG generalize to substance
      use disorders. Response perseveration and reward/punishment sensitivity were
      measured with a probabilistic reversal-learning task, in which subjects could win
      and lose money. Executive functioning was measured with a planning task, the
      Tower of London. Performance and fMRI data were acquired in 19 problem gamblers,
      19 smokers, and 19 healthy controls. Problem gamblers showed severe response
      perseveration, associated with reduced activation of right ventrolateral
      prefrontal cortex in response to both monetary gain and loss. Results did not
      fully generalize to smokers. Planning performance and related activation of the
      dorsal frontostriatal circuit were intact in both problem gamblers and smokers.
      PG is related to response perseveration and diminished reward and punishment
      sensitivity as indicated by hypoactivation of the ventrolateral prefrontal cortex
      when money is gained and lost. Moreover, intact planning abilities and normal
      dorsal frontostriatal responsiveness indicate that this deficit is not due to
      impaired executive functioning. Response perseveration and ventral prefrontal
      hyporesponsiveness to monetary loss may be markers for maladaptive behavior seen
      in chemical and nonchemical addictions.

PMID- 18830240
TI  - Removing obstacles in neuroscience drug discovery: the future path for animal
      models.
AB  - Despite great advances in basic neuroscience knowledge, the improved
      understanding of brain functioning has not yet led to the introduction of truly
      novel pharmacological approaches to the treatment of central nervous system (CNS)
      disorders. This situation has been partly attributed to the difficulty of
      predicting efficacy in patients based on results from preclinical studies. To
      address these issues, this review critically discusses the traditional role of
      animal models in drug discovery, the difficulties encountered, and the reasons
      why this approach has led to suboptimal utilization of the information animal
      models provide. The discussion focuses on how animal models can contribute most
      effectively to translational medicine and drug discovery and the changes needed
      to increase the probability of achieving clinical benefit. Emphasis is placed on
      the need to improve the flow of information from the clinical/human domain to the
      preclinical domain and the benefits of using truly translational measures in both
      preclinical and clinical testing. Few would dispute the need to move away from
      the concept of modeling CNS diseases in their entirety using animals. However,
      the current emphasis on specific dimensions of psychopathology that can be
      objectively assessed in both clinical populations and animal models has not yet
      provided concrete examples of successful preclinical-clinical translation in CNS
      drug discovery. The purpose of this review is to strongly encourage ever more
      intensive clinical and preclinical interactions to ensure that basic science
      knowledge gained from improved animal models with good predictive and construct
      validity readily becomes available to the pharmaceutical industry and clinical
      researchers to benefit patients as quickly as possible.

PMID- 18830242
TI  - Early origins and evolution of microRNAs and Piwi-interacting RNAs in animals.
AB  - In bilaterian animals, such as humans, flies and worms, hundreds of microRNAs
      (miRNAs), some conserved throughout bilaterian evolution, collectively regulate a
      substantial fraction of the transcriptome. In addition to miRNAs, other
      bilaterian small RNAs, known as Piwi-interacting RNAs (piRNAs), protect the
      genome from transposons. Here we identify small RNAs from animal phyla that
      diverged before the emergence of the Bilateria. The cnidarian Nematostella
      vectensis (starlet sea anemone), a close relative to the Bilateria, possesses an
      extensive repertoire of miRNA genes, two classes of piRNAs and a complement of
      proteins specific to small-RNA biology comparable to that of humans. The
      poriferan Amphimedon queenslandica (sponge), one of the simplest animals and a
      distant relative of the Bilateria, also possesses miRNAs, both classes of piRNAs
      and a full complement of the small-RNA machinery. Animal miRNA evolution seems to
      have been relatively dynamic, with precursor sizes and mature miRNA sequences
      differing greatly between poriferans, cnidarians and bilaterians. Nonetheless,
      miRNAs and piRNAs have been available as classes of riboregulators to shape gene
      expression throughout the evolution and radiation of animal phyla.

PMID- 18830243
TI  - Oligopotent stem cells are distributed throughout the mammalian ocular surface.
AB  - The integrity of the cornea, the most anterior part of the eye, is indispensable
      for vision. Forty-five million individuals worldwide are bilaterally blind and
      another 135 million have severely impaired vision in both eyes because of loss of
      corneal transparency; treatments range from local medications to corneal
      transplants, and more recently to stem cell therapy. The corneal epithelium is a
      squamous epithelium that is constantly renewing, with a vertical turnover of 7 to
      14 days in many mammals. Identification of slow cycling cells (label-retaining
      cells) in the limbus of the mouse has led to the notion that the limbus is the
      niche for the stem cells responsible for the long-term renewal of the cornea;
      hence, the corneal epithelium is supposedly renewed by cells generated at and
      migrating from the limbus, in marked opposition to other squamous epithelia in
      which each resident stem cell has in charge a limited area of epithelium. Here we
      show that the corneal epithelium of the mouse can be serially transplanted, is
      self-maintained and contains oligopotent stem cells with the capacity to generate
      goblet cells if provided with a conjunctival environment. Furthermore, the entire
      ocular surface of the pig, including the cornea, contains oligopotent stem cells
      (holoclones) with the capacity to generate individual colonies of corneal and
      conjunctival cells. Therefore, the limbus is not the only niche for corneal stem
      cells and corneal renewal is not different from other squamous epithelia. We
      propose a model that unifies our observations with the literature and explains
      why the limbal region is enriched in stem cells.

PMID- 18830245
TI  - Squeezing and entanglement in a Bose-Einstein condensate.
AB  - Entanglement, a key feature of quantum mechanics, is a resource that allows the
      improvement of precision measurements beyond the conventional bound attainable by
      classical means. This results in the standard quantum limit, which is reached in
      today's best available sensors of various quantities such as time and position.
      Many of these sensors are interferometers in which the standard quantum limit can
      be overcome by using quantum-entangled states (in particular spin squeezed
      states) at the two input ports. Bose-Einstein condensates of ultracold atoms are
      considered good candidates to provide such states involving a large number of
      particles. Here we demonstrate spin squeezed states suitable for atomic
      interferometry by splitting a condensate into a few parts using a lattice
      potential. Site-resolved detection of the atoms allows the measurement of the
      atom number difference and relative phase, which are conjugate variables. The
      observed fluctuations imply entanglement between the particles, a resource that
      would allow a precision gain of 3.8 dB over the standard quantum limit for
      interferometric measurements. 

PMID- 18830244
TI  - The essential role of the CopN protein in Chlamydia pneumoniae intracellular
      growth.
AB  - Bacterial virulence determinants can be identified, according to the molecular
      Koch's postulates, if inactivation of a gene associated with a suspected
      virulence trait results in a loss in pathogenicity. This approach is commonly
      used with genetically tractable organisms. However, the current lack of tools for
      targeted gene disruptions in obligate intracellular microbial pathogens seriously
      hampers the identification of their virulence factors. Here we demonstrate an
      approach to studying potential virulence factors of genetically intractable
      organisms, such as Chlamydia. Heterologous expression of Chlamydia pneumoniae
      CopN in yeast and mammalian cells resulted in a cell cycle arrest, presumably
      owing to alterations in the microtubule cytoskeleton. A screen of a small
      molecule library identified two compounds that alleviated CopN-induced growth
      inhibition in yeast. These compounds interfered with C. pneumoniae replication in
      mammalian cells, presumably by 'knocking out' CopN function, revealing an
      essential role of CopN in the support of C. pneumoniae growth during infection.
      This work demonstrates the role of a specific chlamydial protein in virulence.
      The chemical biology approach described here can be used to identify virulence
      factors, and the reverse chemical genetic strategy can result in the
      identification of lead compounds for the development of novel therapeutics.

PMID- 18830246
TI  - The autonomic nervous system in patients with spinal cord lesion.

PMID- 18830247
TI  - The effect of feeding experience on clinical outcomes in preterm infants.
AB  - OBJECTIVE: The purpose of this analysis was to investigate the effect of oral
      feeding experience on clinical outcomes (time to full oral feedings and length of
      stay) in preterm infants. STUDY DESIGN: This analysis was completed on 92 infants
      who participated in a longitudinal, non-experimental study. Data were collected
      daily for maturity, weight and experience at oral feeding. Additional data were
      collected to assess overall morbidity. RESULT: Time to full oral feedings was
      predicted by experience at oral feeding and morbidity. Length of stay from the
      start of oral feedings until discharge was predicted by feeding experience and by
      maturity at the first oral feeding. Weight gain was not affected by feeding
      experience. CONCLUSION: Experience at feeding may result in more rapid transition
      to full oral feedings regardless of severity of illness and may contribute to
      shorter length of stay. These positive clinical outcomes related to feeding
      experience warrant further research attention.

PMID- 18830248
TI  - Conditional analyses on the T1DGC MHC dataset: novel associations with type 1
      diabetes around HLA-G and confirmation of HLA-B.
AB  - The major histocompatibility complex (MHC) is known to harbour genetic risk
      factors for type 1 diabetes (T1D) additional to the class II determinants HLA
      DRB1, -DQA1 and -DQB1, but strong linkage disequilibrium (LD) has made efforts to
      establish their location difficult. This study utilizes a dataset generated by
      the T1D genetics consortium (T1DGC), with genotypes for 2965 markers across the
      MHC in 2321 T1D families of multiple (mostly Caucasian) ethnicities. Using a
      comprehensive approach consisting of complementary conditional methods and LD
      analyses, we identified three regions with T1D association, independent both of
      the known class II determinants and of each other. A subset of polymorphisms that
      could explain most of the association in each region included single nucleotide
      polymorphisms (SNPs) in the vicinity of HLA-G, particular HLA-B and HLA-DPB1
      alleles, and SNPs close to the COL11A2 and RING1 genes. Apart from HLA-B and HLA
      DPB1, all of these represent novel associations, and subpopulation analyses did
      not indicate large population-specific differences among Caucasians for our
      findings. On account of the unusual genetic complexity of the MHC, further fine
      mapping is demanded, with the possible exception of HLA-B. However, our results
      mean that these efforts can be focused on narrow, defined regions of the MHC.

PMID- 18830249
TI  - The sweet side of immunology: glycobiology of the immune system.

PMID- 18830250
TI  - Association between renin-angiotensin system gene polymorphism and essential
      hypertension: a community-based study.
AB  - Renin-angiotensin (RAS) genes, a group of promising candidate genes involved in
      essential hypertension (EH), play a key role in blood pressure regulation.
      Recently, a series of novel RAS gene polymorphisms were reported, which
      significantly influence the rate of the gene transcription. This study was
      designed to explore the association between the RAS gene polymorphisms and EH in
      a remote countryside population. We examined six polymorphisms in the main
      component genes of RAS: angiotensin-converting enzyme (ACE) (I/D),
      angiotensinogen (AGT) (A-6G, A-20C, G-217A and T174 M) and angiotensin type 1
      receptor (AT1R) (A1166C). Six polymorphisms were genotyped by gene chip
      technology. Association studies were performed in 220 EH patients and 235
      normotensives. Our results revealed that AGT A-6G, T174 M and ACE-I/D were
      significantly associated with EH (AGT A-6G: AG+GG vs AA; OR=1.36; 95% CI=1.04
      1.77. T174M: CT+TT vs CC; OR=1.45; 95% CI=1.15-1.90. ACE I/D: ID+DD vs II;
      OR=1.171; 95% CI=1.00-1.37). Moreover the logistic regression analysis suggested
      that the haplotype of AGT -6A, 174C, -217G and -20A might decrease the risk of EH
      (OR=0.64; 95% CI=0.49-0.83), after adjusting the confounding factors of gender,
      age and BMI. In conclusion, the AGT A-6G, T174 M and ACE I/D polymorphisms are
      associated with EH and the AGT haplotype -6A, 174C, -217G and -20A decrease the
      risk of EH in the southern Chinese population.

PMID- 18830251
TI  - Peripheral arterial disease and isolated systolic hypertension: the ATTEST study.
AB  - Hypertension is a risk factor for cardiovascular (CV) diseases, either coronary
      artery disease (CAD), peripheral artery disease (PAD) or cerebrovascular disease
      (CVD). The relationships between those different localizations of CV disease and
      the haemodynamic features of hypertension have been poorly evaluated in the past.
      In the ATTEST study, a geographically representative panel of 3020 general
      practitioners recruited 8316 consecutive patients with CV diseases (PAD, CAD or
      CVD, alone or in association). Blood pressure, which was not an inclusion
      criterion, was then measured and related to the different forms of CV diseases.
      Blood pressure classification involved 20% normotensive subjects, 24% subjects
      with controlled hypertension, 42% subjects with isolated systolic hypertension
      and 14% subjects with systolic-diastolic hypertension, all hypertensives with or
      without antihypertensive therapy. From multiple regression analysis, it appeared
      that subjects with systolic hypertension were characterized by the presence of
      PAD, with little or no presence of CAD and/or CVD. Subjects with systolic
      diastolic hypertension were characterized by the presence of CAD and/or CVD, but
      without PAD. Although the former was only influenced by age, dyslipidaemia and
      diabetes mellitus influenced the latter. This study confirms the high prevalence
      of hypertension (80%) in a large population of patients with CV diseases selected
      in primary care. Analysis of different features of hypertension revealed that
      isolated systolic hypertension was the most prevalent form of hypertension in
      this treated population. Finally, one of the predominant goals of secondary
      prevention in subjects with PAD should be the treatment of isolated systolic
      hypertension.

PMID- 18830252
TI  - Ethnic variation in hypertension prevalence of women in Taiwan.
AB  - The prevalence and risk factors of hypertension vary in ethnic groups. This study
      aimed to estimate the hypertension prevalence and to compare risk factors
      associated with hypertension in women of four ethnic groups in Taiwan. The study
      subjects were participants in the Taiwanese Survey on Hypertension, Hyperglycemia
      and Hyperlipidemia (TwSHHH) enrolled in 2002. In this analysis, only 2810 women
      who were at age of 20-80 years old and whose father and mother had same ethnic
      background (Minnan, Hakka, Aborigines or Mainland Chinese) were included. Results
      showed that there were significant ethnic differences in the prevalence of
      hypertension, obesity indices, fasting glucose, dyslipidaemia, hyperuricaemia,
      history of alcohol drinking and tobacco smoking and socioeconomic status.
      Aborigines had the highest prevalence of hypertension (28.6%) and diabetes
      mellitus (8.9%), whereas the Minnan group had the second highest prevalence of
      hypertension (19.2%) and diabetes mellitus (7.9%). Both age and central obesity
      were associated with an increased prevalence of hypertension except central
      obesity in Mainland Chinese in all four ethnic groups. Compared with the Mainland
      Chinese as the referent, the multivariate-adjusted odds ratio (OR) (95% CI) was
      1.19 (0.63-2.26), 1.92 (1.15-3.21) and 2.03 (1.00-4.12) for Hakka, Minnan and
      Aborigines, respectively. Elevated body mass index (>or=27.0 vs <24.0 kg m(-2))
      and central obesity were significantly associated with hypertension showing
      multivariate-adjusted OR (95% CI) of 1.68 (1.18-2.38) and 1.95 (1.48-2.57),
      respectively. In addition, dyslipidaemia, hyperuricaemia and diabetes associated
      with higher OR for hypertension in Minnan women. In conclusion, there were ethnic
      variations in hypertension prevalence and determinants in Taiwanese women.

PMID- 18830253
TI  - Feasibility of NIH consensus criteria for chronic graft-versus-host disease.
AB  - To assess the applicability of the National Institutes of Health (NIH) consensus
      criteria (NCC) for chronic graft-versus-host disease (cGVHD), 211 patients who
      developed GVHD more than 100 days after allogeneic transplantation were
      reclassified using NCC. Classifications were: late acute GVHD (44 patients, 21%),
      overlap syndrome (64 patients, 30%) and classic cGVHD (103 patients, 49%).
      Classic cGVHD and overlap syndrome patients (n=167) were graded using both the
      revised Seattle criteria (RSC) and NIH global scoring (NGS). Twenty-three
      patients (14%) had mild, 81 (48%) had moderate and 63 (38%) had severe cGVHD.
      After a median follow-up of 46 months (range 5-71 months), the 4-year GVHD
      specific survival was not significantly different among the different subtypes of
      NCC. Among patients with late acute GVHD, however, the pattern of acute GVHD
      onset (late, persistent or recurrent) was significantly different with respect to
      GVHD-specific survival. Among patients with overlap syndrome and classic cGVHD,
      multivariate analysis showed that NGS as well as RSC were useful in predicting
      survival and discontinuation of immunosuppressive therapy despite of more
      detailed grouping. Our study indicates that NCC is applicable. The clinical
      impact of NIH types and NGS should be verified through prospective studies.

PMID- 18830254
TI  - MafB oncoprotein detected by immunohistochemistry as a highly sensitive and
      specific marker for the prognostic unfavorable t(14;20) (q32;q12) in multiple
      myeloma patients.

PMID- 18830255
TI  - The key role of stem cell factor/KIT signaling in the proliferation of blast
      cells from Down syndrome-related leukemia.
AB  - Transient leukemia (TL) has been observed in approximately 10% of newborn infants
      with Down syndrome (DS). Although treatment with cytarabine is effective in high
      risk TL cases, approximately 20% of severe patients still suffer early death. In
      this study, we demonstrate abundant KIT expression in all 13 patients with GATA1
      mutations, although no significant difference in expression levels was observed
      between TL and acute myeloid leukemia. Stem cell factor (SCF) stimulated the
      proliferation of the TL cells from five patients and treatment with the tyrosine
      kinase inhibitor imatinib suppressed the proliferation effectively in vitro. To
      investigate the signal cascade, we established the first SCF-dependent, DS
      related acute megakaryoblastic leukemia cell line, KPAM1. Withdrawal of SCF or
      treatment with imatinib induced apoptosis of KPAM1 cells. SCF activated the
      RAS/MAPK and PI3K/AKT pathways, followed by downregulation of the pro-apoptotic
      factor BIM and upregulation of the anti-apoptotic factor MCL1. Although we found
      novel missense mutations of KIT in 2 of 14 TL patients, neither mutation led to
      KIT activation and neither reduced the cytotoxic effects of imatinib. These
      results suggest the essential role of SCF/KIT signaling in the proliferation of
      DS-related leukemia and the possibility of therapeutic benefits of imatinib for
      TL patients.

PMID- 18830256
TI  - A novel quantitative assessment of minimal residual disease in patients with
      acute myeloid leukemia carrying NPM1 (nucleophosmin) exon 12 mutations.

PMID- 18830257
TI  - A bispecific single-chain antibody that mediates target cell-restricted, supra
      agonistic CD28 stimulation and killing of lymphoma cells.
AB  - We have previously reported that r28M, a recombinant bispecific single-chain
      antibody directed to a melanoma-associated proteoglycan (NG2) and the
      costimulatory CD28 molecule on T cells, induced T-cell activation, which resulted
      in tumor-cell killing. T-cell activation did not require a primary signal through
      the T-cell antigen receptor (TCR)/CD3 complex and depended on the presence of NG2
      positive tumor cells. Here, we further investigate this phenomenon of a target
      cell-restricted, supra-agonistic CD28 stimulation with bispecific antibodies. To
      this end, we exchanged the NG2 targeting part of r28M with a single-chain
      antibody directed to the B-cell associated antigen CD20. The resulting bispecific
      single-chain antibody, termed r2820, induced supra-agonistic T-cell activation,
      which required the presence of autologous normal or malignant B cells,
      respectively. Once activated, T cells were capable of destroying lymphoma target
      cells.These findings demonstrate that supra-agonistic CD28 stimulation with
      bispecific single-chain antibodies is a robust and readily reproducible
      phenomenon. In the context of experimental tumor therapy, it may provide a
      valuable alternative to the unrestricted T-cell activation induced by 'super
      agonistic', monospecific CD28 antibodies.

PMID- 18830258
TI  - PET imaging of T cells derived from umbilical cord blood.

PMID- 18830259
TI  - PD-1/PD-L1 expression in human T-cell leukemia virus type 1 carriers and adult T
      cell leukemia/lymphoma patients.
AB  - Adult T-cell leukemia/lymphoma (ATLL) develops after infection with human T-cell
      leukemia virus-1 (HTLV-1) after a long latency period. The negative regulatory
      programmed death-1/programmed death-1 ligand 1 (PD-1/PD-L1) pathway has been
      implicated in the induction of cytotoxic T-lymphocyte (CTL) exhaustion during
      chronic viral infection along with tumor escape from host immunity. To determine
      whether the PD-1/PD-L1 pathway could be involved in the establishment of
      persistent HTLV-1 infections and immune evasion of ATLL cells in patients, we
      examined PD-1/PD-L1 expression on cells from 27 asymptomatic HTLV-1 carriers
      (ACs) and 27 ATLL patients in comparison with cells from 18 healthy donors. PD-1
      expression on HTLV-1-specific CTLs from ACs and ATLL patients was dramatically
      elevated. In addition, PD-1 expression was significantly higher on CD8+ T cells
      along with cytomegalovirus (CMV)- and Epstein-Barr virus (EBV)-specific CTLs in
      ATLL patients compared with ACs and control individuals. Primary ATLL cells in
      21.7% of ATLL patients expressed PD-L1, whereas elevated expression was not
      observed in cells from ACs. Finally, in functional studies, we observed that an
      anti-PD-L1 antagonistic antibody upregulated HTLV-1-specific CD8+T-cell response.
      These observations suggest that the PD-1/PD-L1 pathway plays a role in fostering
      persistent HTLV-1 infections, which may further ATLL development and facilitate
      immune evasion by ATLL cells.

PMID- 18830260
TI  - Does chemotherapy modify the immune surveillance of hematological malignancies?
AB  - Malignant diseases induce immune responses against them which have variable
      success in controlling progression of disease. A variety of congenital and
      acquired disorders provide evidence in support of T cell or NK cell immune
      surveillance mechanisms in human hematological malignancies. Furthermore,
      clinical experience with stem cell transplantation underlines the potential for
      both T and NK cell-mediated antileukemia effects. Animal models of tumor
      surveillance and viral-driven lymphoproliferative diseases in man emphasize the
      dynamic nature of the equilibrium between tumors and the immune system, which can
      lead to tumor escape in individuals with normal immune function. In hematological
      malignancies the implication of a dynamic immune surveillance model is that
      chemotherapy may disrupt potentially competent immune surveillance mechanisms
      leading to disease recurrence following successful tumor bulk reduction by
      chemotherapy. This possibility deserves further investigation with a view to
      developing strategies to boost immune function following chemotherapy so as to
      combine the beneficial effect of chemotherapy with an immune response capable of
      sustaining remissions.

PMID- 18830261
TI  - Asymptomatic kidney stones in long-term survivors of childhood acute
      lymphoblastic leukemia.
AB  - We hypothesized an association between renal calculi and bone mineral density
      (BMD) deficits, shown in adults, exists in survivors of childhood acute
      lymphoblastic leukemia (ALL). Thus, we analyzed the associations between
      quantitative computed tomography (QCT)-determined renal calcifications and
      clinical parameters (gender, race, age at diagnosis and age at the time of QCT),
      BMD, treatment exposures and Tanner stage. We investigated the associations
      between stone formation and nutritional intake, serum and urinary calcium and
      creatinine levels, and urinary calcium/creatinine ratio. Exact chi(2)-test was
      used to compare categorical patient characteristics, and the Wilcoxon-Mann
      Whitney test to compare continuous measurements. Of 424 participants, 218 (51.4%)
      were males; 371 (87.5%) were nonblack. Most (n=270; 63.7%) were >or=3.5 years at
      ALL diagnosis. Mean (s.d.) and median (range) BMD Z-scores of the entire cohort
      were -0.4 (1.2) and -0.5 (-3.9 to 5.1), respectively. Nineteen participants (10
      males; 10 Caucasians) had kidney stones (observed prevalence of 4.5%; 19/424)
      with a significant negative association between stone formation and body habitus
      (body mass index, P=0.003). Stone formation was associated with treatment
      protocol (P=0.009) and treatment group (0.007). Thus, kidney stones in childhood
      ALL survivors could herald the future deterioration of renal function and
      development of hypertension. Long-term follow-up imaging may be warranted in
      these patients to monitor for progressive morbidity.

PMID- 18830262
TI  - Stimulation of B-cell lymphoproliferations with CpG-oligonucleotide DSP30 plus IL
      2 is more effective than with TPA to detect clonal abnormalities.

PMID- 18830263
TI  - Polymorphisms in DNA repair and one-carbon metabolism genes and overall survival
      in diffuse large B-cell lymphoma and follicular lymphoma.

PMID- 18830264
TI  - A role for IFN-lambda1 in multiple myeloma B cell growth.
AB  - Multiple myeloma (MM) is a progressive disease that results from dysregulated
      proliferation of plasma cells. Although, causative factors such as genetic events
      and altered expression of anti-apoptotic factors have been described in a number
      of patients, the mechanistic details that drive myeloma development and continued
      growth of malignant cells remain largely undefined. Numerous growth factors,
      including interleukin (IL)-6, Insulin-like growth factor-1 and IL-10 have been
      shown to promote growth of MM cells suggesting a significant role for cytokines
      in this disease. Interferon (IFN)-lambda1 is a new member of the Class II
      cytokine family that, similar to IFN-alpha, has been shown to mediate viral
      immunity. In light of data supporting a role for cytokines in myeloma, we
      investigated the significance of IFN-lambda1 on myeloma cell biology. Our studies
      show for the first time that myeloma cells bind to soluble IFN-lambda1, and that
      IFN-lambda1 induces myeloma cell growth and protects against dexamethasone
      induced cell death. Our data also show that IFN-lambda1 induces phosphorylation
      of STAT1, STAT3 and Erk. Taken together, our results suggest that IFN-lambda1 may
      regulate myeloma cell biology and could prove to be therapeutically important.

PMID- 18830265
TI  - Aberrant GM-CSF signal transduction pathway in juvenile myelomonocytic leukemia
      assayed by flow cytometric intracellular STAT5 phosphorylation measurement.

PMID- 18830266
TI  - Calcium ion gradients and dynamics in cultured skin slices of rat hindpaw in
      response to stimulation with ATP.
AB  - Ionotropic receptors, originally found in the brain, were recently also
      identified in epidermal keratinocytes. Moreover, concentration gradients and
      movement of calcium are crucial in epidermal homeostasis. Thus, imaging of
      calcium in the living epidermis is expected to provide insight into epidermal
      physiology and pathology. Here we describe the imaging of calcium dynamics in the
      living epidermis of cultured skin slices. The basal calcium concentration was
      highest in the upper layer of the epidermis. The increase of intracellular
      calcium in response to adenosine triphosphate (ATP) varied in each layer of
      epidermis, and was greater at the bottom than in the uppermost layer. Further,
      the extent of elevation of intracellular calcium in response to ATP in cultured
      keratinocytes varied depending on the level of differentiation. These results
      suggest that the response to stimulation of keratinocytes in cultured skin slices
      varies depending upon the location (depth) within the epidermis.

PMID- 18830267
TI  - Genetic variations in cytokines and cytokine receptors associated with psoriasis
      found by genome-wide association.
AB  - Genetic variants have long been suspected to be important in psoriasis. Recent
      work has suggested that HLA-Cw6 on chromosome 6 is the risk variant in the PSORS1
      [MIM 177900] susceptibility locus that confers the greatest risk for early onset
      of psoriasis. Although numerous minor susceptibility loci have been identified by
      linkage analysis, few biologically relevant candidates have been discovered
      within these intervals. Recent large-scale genome-wide association studies have
      yielded new candidates in genes encoding cytokines with functional relevance to
      psoriasis. Polymorphisms within the genes encoding the IL-12 p40 subunit, IL12B,
      and one of the IL-23 receptor subunits, IL23R, have been replicated in US and
      European populations and overlap with risk of Crohn's disease. Polymorphisms
      within the gene encoding IL-13, a Th2 cytokine, also confer risk for psoriasis.
      Variants of the gene IL15 encoding IL-15 have been identified that associate with
      psoriasis in a Chinese population. These discoveries pose the challenge of
      elucidating the role of common genetic variants in susceptibility to and
      manifestations of psoriasis.

PMID- 18830268
TI  - Mutations in the lipase H gene underlie autosomal recessive woolly
      hair/hypotrichosis.
AB  - Woolly hair (WH) is characterized by the presence of fine and tightly curled
      hair. WH can appear as a symptom of some systemic diseases, or without associated
      findings (nonsyndromic WH). Nonsyndromic WH is known to be inherited as either an
      autosomal-dominant (OMIM 194300) or recessive (ARWH; OMIM 278150) trait. In this
      study, we identified 11 consanguineous families of Pakistani origin with ARWH, as
      well as associated features including sparse and hypopigmented hair shafts. We
      first checked for mutations in the P2RY5 gene, which encodes an orphan G-protein
      coupled receptor that we recently identified as a cause of ARWH. However, none of
      the 11 families had mutations in the P2RY5 gene. To identify the disease locus,
      we performed linkage studies in one of these families using the Affymetrix 10K
      array, and identified a region of suggestive linkage on chromosome 3q27. This
      region contains the lipase H (LIPH) gene which has been recently shown to
      underlie an autosomal-recessive form of hypotrichosis. Mutation analysis resulted
      in the identification of a total of 5 pathogenic mutations in the LIPH of all 11
      families analyzed. These results show that LIPH is a second causative gene for
      ARWH/hypotrichosis, giving rise to a phenotype clinically indistinguishable from
      P2RY5 mutations.

PMID- 18830269
TI  - Auf1/Hnrnpd-deficient mice develop pruritic inflammatory skin disease.
AB  - Mice lacking heterogenous nuclear ribonuclear protein D (Hnrnpd), also known as
      Auf1, a regulator of inflammatory cytokine mRNA stability, develop chronic
      dermatitis with age that is characterized by pruritus and excoriations.
      Histological analysis showed marked epidermal acanthosis and spongiosis,
      neovascularization, and elevated number of inflammatory cells, including T cells,
      macrophages, neutrophils, mast cells, and eosinophils. Hnrnpd-deficient
      (Hnrnpd(tm1Rjsc)) mice with dermatitis display elevated serum IgE levels. Lesions
      in Hnrnpd(tm1Rjsc) mice were associated with a shift towards a Th(2) immune
      environment. Evaluation of T-cell-mediated skin inflammation by assaying contact
      hypersensitivity indicated an increased response in Hnrnpd(tm1Rjsc) mice. T cells
      and macrophages from Hnrnpd(tm1Rjsc) mice demonstrate a number of abnormalities
      associated with dermatitis, including increased IL2, tumor-necrosis factor-alpha
      (TNFalpha), and IL1beta production. Finally, many features of spontaneous
      dermatitis could be recapitulated in experimentally induced lesions by
      subcutaneous injection of CCL27 and TNF in unaffected Hnrnpd(tm1Rjsc) mice.
      Collectively, these data highlight the importance of HNRNPD and proper regulation
      of mRNA stability in the intricate processes of leukocyte recruitment and
      inflammatory activation within the skin.

PMID- 18830270
TI  - Chronic mouse model of TMA-induced contact hypersensitivity.
AB  - Due to the steadily increasing incidence of atopic dermatitis (AD), especially in
      children, there is a high medical need for new therapies and improved animal
      models. In mice, trimellitic anhydride (TMA) is routinely used to trigger T-cell
      dependent contact hypersensitivity (CHS) reactions. In this study, we compared
      the standard acute TMA-induced CHS in Balb/c mice with subacute and chronic
      models of TMA-induced ear inflammation. Compared to the acute model, the chronic
      CHS model more closely reflects characteristics of AD, such as typical
      morphological changes of the inflamed skin, strong infiltration with T cells,
      major histocompatibility complex II-positive cells, eosinophils, and mast cells,
      a T-helper cell-type (Th) 2 cytokine profile and a strong increase of serum IgE
      levels. Moreover, a strong lymph node involvement with T-helper cell dominance
      and a mixed Th1/Th2 T-cell differentiation and activation pattern was
      demonstrated. Importantly, as demonstrated by successful therapy with
      prednisolone, the chronic TMA-induced CHS model, in contrast to acute and
      subacute models, made prolonged therapeutic treatment of a pre-established skin
      inflammation possible. Altogether, we present an improved model of mouse T-cell
      dependent skin inflammation for AD. We hope this model will enhance the
      predictive value of animal models for therapeutic treatment of atopic eczema.

PMID- 18830271
TI  - Functional characterization of IL-17F as a selective neutrophil attractant in
      psoriasis.
AB  - IL-17F is known to be involved in many inflammatory diseases, but its role in
      skin diseases has not been fully examined. Because IL-8 is involved in many skin
      diseases such as psoriasis, we investigated the production of IL-8 in normal
      human epidermal keratinocytes (NHEKs) stimulated by IL-17F, tumor necrosis factor
      alpha (TNF-alpha), IL-17A, and control using real-time PCR and ELISA. The results
      showed that IL-17F induced production of IL-8 in NHEKs in a time-dependent
      manner. Interestingly, the amounts of IL-8 stimulated by IL-17F were much higher
      than those stimulated by TNF-alpha or IL-17A. Next, we confirmed that selective
      mitogen-activated protein kinase kinase inhibitors significantly inhibited IL-17F
      induced IL-8 production. Moreover, mouse skin intradermally injected with IL-17F
      expressed high level of IL-8 mRNA and induced ERK1/2 phosphorylation.
      Histological examination of mouse skin that was injected with IL-17F revealed
      marked neutrophilia in dermis and the infiltration was significantly inhibited by
      anti-IL-8 antibody. Finally, IL-17F expression in skin biopsy samples from
      psoriasis patients were examined by western blotting and ELISA. IL-17F was
      upregulated in lesional psoriatic skin compared with nonlesional skin. These
      results indicate that IL-17F may be involved in psoriasis via, in part, the
      activation of ERK1/2 and the induction of IL-8 in keratinocytes.

PMID- 18830272
TI  - The EGFR is required for proper innervation to the skin.
AB  - EGFR family members are essential for proper peripheral nervous system
      development. A role for EGFR itself in peripheral nervous system development in
      vivo, however, has not been reported. We investigated whether EGFR is required
      for cutaneous innervation using Egfr null and skin-targeted Egfr mutant mice.
      Neuronal markers; including PGP9.5, GAP-43, acetylated tubulin, and
      neurofilaments; revealed that Egfr null dorsal skin was hyperinnervated with a
      disorganized pattern of innervation. In addition, receptor subtypes such as
      lanceolate endings were disorganized and immature. To determine whether the
      hyperinnervation phenotype resulted from a target-derived effect of loss of EGFR,
      mice lacking EGFR expression in the cutaneous epithelium were examined. These
      mice retained other aspects of the cutaneous Egfr null phenotype but exhibited
      normal innervation. The sensory deficits in Egfr null dorsal skin were not
      associated with any abnormality in the morphology or density of dorsal root
      ganglion (DRG) neurons or Schwann cells. However, explant and dissociated cell
      cultures of DRG revealed more extensive branching in Egfr null cultures. These
      data demonstrate that EGFR is required for proper cutaneous innervation during
      development and suggest that it limits axonal outgrowth and branching in a DRG
      autonomous manner.

PMID- 18830273
TI  - Transgenic expression of interleukin-13 in the skin induces a pruritic dermatitis
      and skin remodeling.
AB  - IL-13 has been implicated in the pathogenesis of allergic diseases, including
      atopic dermatitis (AD). However, a direct role of IL-13 in AD has not been
      established. We aimed to develop an inducible transgenic model in which IL-13 can
      be expressed in the skin and to define the resulting dermal phenotype and
      mechanisms involved. The keratin 5 promoter was used with a tetracycline
      inducible system to target IL-13 to the skin. The clinical manifestations, dermal
      histology, cytokine gene regulation, and systemic immune responses in the
      transgenic mice were assessed. IL-13 was produced exclusively in the skin and
      caused a chronic inflammatory phenotype characterized by xerosis and pruritic
      eczematous lesions; dermal infiltration of CD4+ T cells, mast cells, eosinophils,
      macrophages, and Langerhans cells; upregulation of chemokine and cytokine genes,
      including thymic stromal lymphopoietin; and skin remodeling with fibrosis and
      increased vasculature. The dermal phenotype was accompanied by elevated serum
      total IgE and IgG1 and increased production of IL-4 and IL-13 by CD4+ cells from
      lymphoid tissues and peripheral blood mononuclear cells. IL-13 is a potent
      stimulator of dermal inflammation and remodeling and this transgenic model of AD
      is a good tool for investigating the underlying mechanisms in the pathogenesis of
      AD.

PMID- 18830274
TI  - Cystic fibrosis: ferreting with fibroblasts for cystic fibrosis.

PMID- 18830275
TI  - The ecological proportion of indigenous bacterial populations in saliva is
      correlated with oral health status.
AB  - To obtain deeper insights into the etiology of oral disease, an understanding of
      the composition of the surrounding bacterial environments that lead to health or
      disease is required, which is attracting increasing attention. In this study, the
      bacterial compositions in the saliva of 200 subjects aged 15-40 years were
      depicted as peak patterns by terminal restriction fragment length polymorphism (T
      RFLP) analysis of 16S rRNA genes. The subjects were classified into three
      clusters by partitioning around medoids clustering based on their T-RFLP
      profiles, and the clinical oral health parameters of the clusters were compared.
      The clustering of the T-RFLP profiles in this study was mainly based on
      differences in the abundance distribution of the dominant terminal restriction
      fragments (TRFs) detected in most of the subjects. Predicted from the sizes of
      the TRFs, the characteristically more predominant members of each were Prevotella
      and Veillonella species in cluster I; Streptococcus species in cluster II and
      Neisseria, Haemophilus or Aggregatibacter species and Porphyromonas species in
      cluster III. The parameters associated with periodontal disease were
      significantly different among the clusters. Clusters I and II had a higher
      percentage of sites of periodontal pockets greater than 4 mm than cluster III,
      and cluster I contained sites exhibiting bleeding on probing more often than
      cluster II or III; no significant differences were observed in other parameters.
      These results suggest that the abundance distribution of commensal bacteria in
      saliva is correlated with periodontal health, and might be involved in the
      susceptibility of an individual to periodontal disease.

PMID- 18830276
TI  - Interaction of Salmonella enterica with basil and other salad leaves.
AB  - Contaminated salad leaves have emerged as important vehicles for the transmission
      of enteric pathogens to humans. A recent outbreak of Salmonella enterica serovar
      Senftenberg (S. Senftenberg) in the United Kingdom has been traced to the
      consumption of contaminated basil. Using the outbreak strain of S. Senftenberg,
      we found that it binds to basil, lettuce, rocket and spinach leaves showing a
      pattern of diffuse adhesion. Flagella were seen linking S. Senftenberg to the
      leaf epidermis, and the deletion of fliC (encoding phase-1 flagella) resulted in
      a significantly reduced level of adhesion. In contrast, although flagella linking
      S. enterica serovar Typhimurium to the basil leaf epidermis were widespread,
      deletion of fliC did not affect leaf attachment levels. These results implicate
      the role of flagella in Salmonella leaf attachment and suggest that different
      Salmonella serovars use strain-specific mechanisms to attach to salad leaves.

PMID- 18830277
TI  - An uncultivated crenarchaeota contains functional bacteriochlorophyll a synthase.
AB  - A fosmid clone 37F10 containing an archaeal 16S rRNA gene was screened out from a
      metagenomic library of Pearl River sediment, southern China. Sequence analysis of
      the 35 kb inserted fragment of 37F10 found that it contains a single 16S rRNA
      gene belonging to Miscellaneous Crenarchaeotal Group (MCG) and 36 open reading
      frames (ORFs). One ORF (orf11) encodes putative bacteriochlorophyll a synthase
      (bchG) gene. Bacteriochlorophyll a synthase gene has never been reported in a
      member of the domain Archaea, in accordance with the fact that no (bacterio)
      chlorophyll has ever been detected in any cultivated archaea. The putative
      archaeal bchG (named as ar-bchG) was cloned and heterologously expressed in
      Escherichia coli. The protein was found to be capable of synthesizing
      bacteriochlorophyll a by esterification of bacteriochlorophyllide a with phytyl
      diphosphate or geranylgeranyl diphosphate. Furthermore, phylogenetic analysis
      clearly indicates that the ar-bchG diverges before the bacterial bchGs. Our
      results for the first time demonstrate that a key and functional enzyme for
      bacteriochlorophyll a biosynthesis does exist in Archaea.

PMID- 18830278
TI  - A comparison of homologous recombination rates in bacteria and archaea.
AB  - It is a standard practice to test for the signature of homologous recombination
      in studies examining the genetic diversity of bacterial populations. Although it
      has emerged that homologous recombination rates can vary widely between species,
      comparing the results from different studies is made difficult by the diversity
      of estimation methods used. Here, Multi Locus Sequence Typing (MLST) datasets
      from a wide variety of bacteria and archaea are analyzed using the ClonalFrame
      method. This enables a direct comparison between species and allows for a first
      exploration of the question whether phylogeny or ecology is the primary
      determinant of homologous recombination rate.

PMID- 18830280
TI  - Influence of atmospheric and sea-surface corrections on retrieval of bottom depth
      and reflectance using a semi-analytical model: a case study in Kaneohe Bay,
      Hawaii.
AB  - Hyperspectral instruments provide the spectral detail necessary for extracting
      multiple layers of information from inherently complex coastal environments. We
      evaluate the performance of a semi-analytical optimization model for deriving
      bathymetry, benthic reflectance, and water optical properties using hyperspectral
      AVIRIS imagery of Kaneohe Bay, Hawaii. We examine the relative impacts on model
      performance using two different atmospheric correction algorithms and two
      different methods for reducing the effects of sunglint. We also examine the
      impact of varying view and illumination geometry, changing the default bottom
      reflectance, and using a kernel processing scheme to normalize water properties
      over small areas. Results indicate robust model performance for most model
      formulations, with the most significant impact on model output being generated by
      differences in the atmospheric and deglint algorithms used for preprocessing.

PMID- 18830279
TI  - Fungal diversity in the rhizosphere of endemic plant species of Tenerife (Canary
      Islands): relationship to vegetation zones and environmental factors.
AB  - Knowledge about fungal diversity scaling relationships relative to that of plants
      is important to understand ecosystem functioning. Tenerife Island, a natural
      laboratory to study terrestrial biodiversity, is represented by six different
      vegetation zones characterized by specific abiotic conditions and plant
      communities with a high proportion of endemic plants. Little is known about the
      biodiversity of associated fungi. To understand the relationship between plant
      and fungal communities, we analysed soil/rhizosphere fungi from all vegetation
      zones. From 12 sampling points dispersed on the whole island, molecular analysis
      of fungal communities was determined by single-strand conformation polymorphism
      (SSCP) analysis using universal and specific primers for Trichoderma. The highly
      diverse fungal communities were mainly characterized by ectomycorrhiza-forming
      Basidiomycota and a high proportion of yet-unidentified species. Besides,
      Trichoderma-specific SSCP resulted in low diversity of mainly cosmopolitan
      species, for example Hypocrea lixii/T. harzianum. The dominance of T. harzianum
      was confirmed by cultivation. All Trichoderma isolates show an extraordinarily
      high antagonistic potential towards different groups of plant pathogens,
      supporting the hypothesis of extensive colonization by highly competitive
      Trichoderma species from the continent. In contrast, biodiversity patterns of the
      whole fungal and plant communities follow the same ecological rules. Furthermore,
      a high statistical correlation between fungal communities and the main
      environmental factors, temperature and precipitation, was found.

PMID- 18830281
TI  - Performance of a long-wave infrared hyperspectral imager using a Sagnac
      interferometer and an uncooled microbolometer array.
AB  - Field and laboratory measurements using an interferometer spectrometer based on
      the Sagnac interferometer using a microbolometer array detector are presented.
      Remotely obtained signatures collected with this instrument and with a cryogenic
      IR spectrometer are compared and shown to closely correspond. Ground-to-ground
      and air-to-ground image products are presented that demonstrate the image quality
      of the sensor. Signal-to-noise measurements are presented and compared with a
      simple parametric performance model that predicts the sensor performance. The
      performance model is used to predict the performance of this technology when
      equipped with cooled detectors.

PMID- 18830282
TI  - Quantitative comparison of quadratic covariance-based anomalous change detectors.
AB  - Simulations applied to hyperspectral imagery from the AVIRIS sensor are employed
      to quantitatively evaluate the performance of anomalous change detection
      algorithms. The evaluation methodology reflects the aim of these algorithms,
      which is to distinguish actual anomalous changes in a pair of images from the
      incidental differences that pervade the entire scene. By simulating both the
      anomalous changes and the pervasive differences, accurate and plentiful ground
      truth is made available, and statistical estimates of detection and false alarm
      rates can be made. Comparing the receiver operating characteristic (ROC) curves
      that encapsulate these rates provides a way to identify which algorithms work
      best under which conditions.

PMID- 18830283
TI  - Airborne hyperspectral detection of small changes.
AB  - Hyperspectral change detection offers a promising approach to detect objects and
      features of remotely sensed areas that are too difficult to find in single
      images, such as slight changes in land cover and the insertion, deletion, or
      movement of small objects, by exploiting subtle differences in the imagery over
      time. Methods for performing such change detection, however, must effectively
      maintain invariance to typically larger image-to-image changes in illumination
      and environmental conditions, as well as misregistration and viewing differences
      between image observations, while remaining sensitive to small differences in
      scene content. Previous research has established predictive algorithms to
      overcome such natural changes between images, and these approaches have recently
      been extended to deal with space-varying changes. The challenges to effective
      change detection, however, are often exacerbated in an airborne imaging geometry
      because of the limitations in control over flight conditions and geometry, and
      some of the recent change detection algorithms have not been demonstrated in an
      airborne setting. We describe the airborne implementation and relative
      performance of such methods. We specifically attempt to characterize the effects
      of spatial misregistration on change detection performance, the efficacy of class
      conditional predictors in an airborne setting, and extensions to the change
      detection approach, including physically motivated shadow transition classifiers
      and matched change filtering based on in-scene atmospheric normalization.

PMID- 18830284
TI  - Correction of systematic spatial noise in push-broom hyperspectral sensors:
      application to CHRIS/PROBA images.
AB  - Hyperspectral remote sensing images are affected by different types of noise. In
      addition to typical random noise, nonperiodic partially deterministic disturbance
      patterns generally appear in the data. These patterns, which are intrinsic to the
      image formation process, are characterized by a high degree of spatial and
      spectral coherence. We present a new technique that faces the problem of removing
      the spatially coherent noise known as vertical striping, usually found in images
      acquired by push-broom sensors. The developed methodology is tested on data
      acquired by the Compact High Resolution Imaging Spectrometer (CHRIS) onboard the
      Project for On-board Autonomy (PROBA) orbital platform, which is a typical
      example of a push-broom instrument exhibiting a relatively high noise component.
      The proposed correction method is based on the hypothesis that the vertical
      disturbance presents higher spatial frequencies than the surface radiance. A
      technique to exclude the contribution of the spatial high frequencies of the
      surface from the destriping process is introduced. First, the performance of the
      proposed algorithm is tested on a set of realistic synthetic images with added
      modeled noise in order to quantify the noise reduction and the noise estimation
      accuracy. Then, algorithm robustness is tested on more than 350 real CHRIS images
      from different sites, several acquisition modes (different spatial and spectral
      resolutions), and covering the full range of possible sensor temperatures. The
      proposed algorithm is benchmarked against the CHRIS reference algorithm. Results
      show excellent rejection of the noise pattern with respect to the original CHRIS
      images, especially improving the removal in those scenes with a natural high
      contrast. However, some low-frequency components still remain. In addition, the
      developed correction model captures and corrects the dependency of the noise
      patterns on sensor temperature, which confirms the robustness of the presented
      approach.

PMID- 18830285
TI  - Automated target detection system for hyperspectral imaging sensors.
AB  - Over the past several years, hyperspectral sensor technology has evolved to the
      point where real-time processing for operational applications is achievable.
      Algorithms supporting such sensors must be fully automated and robust. Our
      approach, for target detection applications, is to select signatures from a
      target reflectance library database and project them to the at-sensor and
      collection-specific radiance domain using the weather forecast or radiosonde
      data. This enables platform-based detection immediately following data
      acquisition without the need for further atmospheric compensation. One advantage
      of this method for reflective hyperspectral sensors is the ability to predict the
      radiance signatures of targets under multiple illumination conditions. A three
      phase approach is implemented, where the library generation and data acquisition
      phases provide the necessary input for the automated detection phase. In addition
      to employing the target detector itself, this final phase includes a series of
      automated filters, adaptive thresholding, and confidence assignments to extract
      the optimal information from the detection scores for each spectral class. Our
      prototype software is applied to 50 reflective hyperspectral datacubes to measure
      detection performance over a range of targets, backgrounds, and environmental
      conditions.

PMID- 18830286
TI  - Design and fabrication of a low-cost, multispectral imaging system.
AB  - This paper reports the design and construction of a low-cost, multispectral
      imaging system using a single, large format CCD and an array of 18 individual
      lenses coupled to individual spectral filters. The system allows the simultaneous
      acquisition of 18 subimages, each with potentially different optical information.
      The subimages are combined to create a composite image, highlighting the desired
      spectral information. Because all the subimages are acquired simultaneously, the
      composite image shows no motion artifact. Although the present configuration uses
      17 narrow bandpass optical filters to obtain multispectral information from a
      scene, the system is designed to be a general purpose, multiaperture platform,
      easily reconfigured for other multiaperture imaging modes.

PMID- 18830287
TI  - End-member extraction for hyperspectral image analysis.
AB  - We investigate the relationship among several popular end-member extraction
      algorithms, including N-FINDR, the simplex growing algorithm (SGA), vertex
      component analysis (VCA), automatic target generation process (ATGP), and fully
      constrained least squares linear unmixing (FCLSLU). We analyze the fundamental
      equivalence in the searching criteria of the simplex volume maximization and
      pixel spectral signature similarity employed by these algorithms. We point out
      that their performance discrepancy comes mainly from the use of a dimensionality
      reduction process, a parallel or sequential implementation mode, or the
      imposition of certain constraints. Instructive recommendations in algorithm
      selection for practical applications are provided.

PMID- 18830288
TI  - Analysis of computed tomographic imaging spectrometers. I. Spatial and spectral
      resolution.
AB  - Computed tomographic imaging spectrometers measure the spectrally resolved image
      of an object scene in an entirely different manner from traditional whisk-broom
      or push-broom systems, and thus their noise behavior and data artifacts are
      unfamiliar. We review computed tomographic imaging spectrometry (CTIS)
      measurement systems and analyze their performance, with the aim of providing a
      vocabulary for discussing resolution in CTIS instruments, by illustrating the
      artifacts present in their reconstructed data and contributing a rule-of-thumb
      measure of their spectral resolution. We also show how the data reconstruction
      speed can be improved, at no cost in reconstruction quality, by ignoring
      redundant projections within the measured raw images.

PMID- 18830289
TI  - Statistical characterization of hyperspectral background clutter in the
      reflective spectral region.
AB  - Hyperspectral imaging systems for daylight operation measure and analyze
      reflected and scattered radiation in p-spectral channels covering the reflective
      infrared region 0.4-2.5 microm. Consequently, the p-dimensional joint
      distribution of background clutter is required to design and evaluate optimum
      hyperspectral imaging processors. In this paper, we develop statistical models
      for the spectral variability of natural hyperspectral backgrounds using the class
      of elliptically contoured distributions. We demonstrate, using data from the NASA
      AVIRIS sensor, that models based on the multivariate t-elliptically contoured
      distribution capture with sufficient accuracy the statistical characteristics of
      natural hyperspectral backgrounds that are relevant to target detection
      applications.

PMID- 18830291
TI  - Method for path imbalance measurement of the two-arm fiber-optic interferometer.
AB  - The path imbalance (PI) of the two-arm fiber-optic interferometric sensor is a
      substantial parameter; a precise value of millimeters is required. Currently the
      precision reflectometry and the millimeter optical time-domain reflectometry are
      used to measure the tiny optical path difference, but the performances of these
      measurements are limited from the length and the resolution of the PI. We propose
      a new method accomplished by interferometer to accurately measure millimeters to
      within a few decimeters of the PI.

PMID- 18830292
TI  - Time-resolved studies of photoinduced birefringence in azobenzene dye-doped
      polymer films.
AB  - We measured transient photoinduced birefringence (delta n) in various azobenzene
      dye films by pumping with a nanosecond pulse at 532 nm and probing at 633 nm. The
      switch-on times for the photoinduced birefringence range from nanoseconds to
      milliseconds and are systematically related with the lowest optical transition
      energies for those films. Moreover, our results suggest that the transient
      photoinduced birefringence measurement is a convenient way to determine the
      relative energies of pi-pi(*) and n-pi(*) states in azo-based materials.

PMID- 18830293
TI  - Comment on the reported fiber attenuations in the visible regime in "Fabrication
      of glass photonic crystal fibers with a die-cast process".
AB  - We comment on the recent paper by Zhou et al. [Appl. Opt.45, 4433
      (2006)APOPAI0003-693510.1364/AO.45.004433], in which transmission losses of 0.2
      0.3 dB/m were claimed across the wavelength range 420-900 nm in a high-index
      (n(d)=1.80518 at 587.6 nm) SF6 glass-based photonic crystal fiber fabricated by
      novel die-cast technique. If confirmed, these losses are at least 1 order of
      magnitude lower than previous reported losses of SF6 photonic crystal fibers from
      other fabrication approaches. Here we present a statistic survey on the
      relationship between the refractive index and the bulk material attenuation,
      based on a large number of commercial Schott optical glasses with the n(d)
      ranging between 1.40 and 2.05. It shows that the loss of a high-index (n(d)=1.80)
      glass optical fiber should be at the levels of 10-50 dB/m at 420 nm and 1-10 dB/m
      at 500 nm, respectively. Moreover, the material attenuation of such a high-index
      glass fiber should intrinsically show a large decay, from 10-50 dB/m at 420 nm to
      the level of 1 dB/m at 700 nm, which arises from the tail on the UV absorption
      edge of the high-index glass extending to the visible region. Therefore, we
      conclude that: (1) the low loss of 0.2-0.3 dB/m reported in the cited paper is
      abnormally one or two magnitudes lower than the material attenuation that a high
      index (n(d)=1.80) glass optical fiber should have in the range between 420 and
      500 nm and that (2) the flat loss curve between 420 and 700 nm in the cited paper
      deviates greatly from the intrinsic behavior of a high-index (n(d)=1.80) glass
      fiber.

PMID- 18830295
TI  - Nanoscale topography of dynamic surfaces with ultrafast time resolution.
AB  - We describe an optical system for detecting the movement of a surface with
      subnanosecond temporal and nanometer vertical displacement resolution. The system
      is fielded on an experiment to determine the distortion of a laser-ablated metal
      layer and compare the results with hydrodynamic simulations. We also discuss
      errors that can arise and potential means to mitigate them. The resultant data
      show one can examine dynamic changes to a reflective surface with accuracy down
      to tens of nanometers at hundreds of picoseconds time resolution.

PMID- 18830296
TI  - Properties of strong anisotropic a-axis single-crystal fiber with an applied
      electric field.
AB  - The effect of an applied electric field on the properties of strongly anisotropic
      a-axis single-crystal fiber is studied theoretically. We solve the
      electromagnetic field equations for strongly anisotropic a-axis single-crystal
      fiber and numerically analyze the mode characteristics of the fiber that conducts
      only the zeroth-order elementary mode. We discuss the effects that an applied
      electric field has on the refractive index anisotropy and the mode
      characteristics of the fiber that conducts only the zeroth-order elementary mode.

PMID- 18830297
TI  - Mode purity comparison of optical vortices generated by a segmented deformable
      mirror and a static multilevel phase plate.
AB  - We present a mode purity comparison between optical vortices (OVs) generated by a
      static multilevel phase plate with 16 or 32 phase steps and a vortex generated
      with a segmented deformable mirror with 37 actuators. Computer simulations show
      the intensity and phase of the vortices generated with the two methods. The
      deformable mirror, by being reconfigurable, shows better mode purity for high
      charge OVs, while the static phase plate mode efficiency declines due to the
      fixed number phase quantization.

PMID- 18830298
TI  - Application of constrained optimization to the design of quasi-rugate optical
      coatings.
AB  - The constrained optimization approach is applied to the design of quasi-rugate
      optical coatings. These coatings are defined as multilayers with no thin layers
      where refractive index profiles resemble rugate-type refractive index profiles
      and where spectral properties are typical for rugate filters. It is shown that
      all design problems that are usually solved using rugate filters can be solved
      successfully in the frame of quasi-rugate optical coatings. Comparison between
      quasi-rugate and two-component multilayer designs is provided.

PMID- 18830299
TI  - Superresolution in dewarped anisoplanatic images.
AB  - I present a simple theoretical model for dewarped imaging through a turbulent
      medium and calculate the degree of superresolution that can be attained by
      dewarping the distorted instantaneous images registered through a turbulent
      atmosphere. The estimates show that on 1 km near the ground propagation path,
      spatial frequencies of the dewarped image can exceed the diffraction limit three
      times with a probability up to 10%.

PMID- 18830300
TI  - Determination of optical parameters of very thin (lambda/50) films.
AB  - A straightforward approach for estimation of thickness (d), real (epsilon(1)) and
      imaginary parts (epsilon(2)) of the complex permittivity of very thin films from
      spectrophotometric measurements is presented. The uncertainties in epsilon(1),
      epsilon(2), and d due to methodical error and the uncertainties in the measured
      quantities are investigated. It is shown that the influence of these factors is
      considerable when epsilon(1), epsilon(2), and d are obtained simultaneously for
      each wavelength. The accuracy of epsilon(1), epsilon(2), and d is significantly
      increased if the value of d is evaluated first, its value is kept constant over
      the whole spectral region, and then epsilon(1) and epsilon(2) are calculated for
      each wavelength.

PMID- 18830301
TI  - Low-cost fiber Bragg grating vibroacoustic sensor for voice and heartbeat
      detection.
AB  - A fiber Bragg grating (FBG) vibroacoustic sensor exploiting an intensity-based
      interrogation principle is presented. The optical system is complemented by
      signal processing techniques that allow disturbances to be mitigated and improve
      the spectral estimation. The sensor is capable of performing frequency analysis
      of sounds up to 3 kHz, with top sensitivity in the 100-500 Hz frequency range,
      and of dynamically tracking pulsed phenomena that induce a strain to the FBG. The
      sensor has been applied to the detection of voice, showing a great
      intelligibility of the speech despite the low-quality environment, and to the
      monitoring of the heartbeat rate from the wrist.

PMID- 18830302
TI  - Characterization of nanostructured GaSb: comparison between large-area optical
      and local direct microscopic techniques.
AB  - Low energy ion-beam sputtering of GaSb results in self-organized nanostructures
      with the potential of structuring large surface areas. Characterization of such
      nanostructures by optical methods is studied and compared to direct (local)
      microscopic methods. The samples consist of densely packed GaSb cones on bulk
      GaSb, approximately 30, 50, and 300 nm in height, prepared by sputtering at
      normal incidence. The optical properties are studied by spectroscopic
      ellipsometry, in the range 0.6-6.5 eV, and with Mueller matrix ellipsometry in
      the visible range, 1.46-2.88 eV. The optical measurements are compared to direct
      topography measurements obtained by scanning electron microscopy, high resolution
      transmission electron microscopy, and atomic force microscopy. Good agreement is
      achieved between the two classes of methods when the experimental optical
      response of the short cones (<55 nm) is inverted with respect to topological
      surface information, via a graded anisotropic effective medium model. The main
      topological parameter measured was the average cone height. Optical methods are
      shown to represent a valuable characterization tool of nanostructured surfaces,
      in particular when a large coverage area is desirable. Because of the fast and
      nondestructive properties of optical techniques, they may readily be adapted to
      in situ configurations.

PMID- 18830303
TI  - Narrowband optical filters suitable for various applications in optical
      communications.
AB  - We propose three types of narrowband optical filters based on a Fox-Smith
      resonator. We demonstrate that by choosing the appropriate combination of coating
      materials on each prism facet, one can design either a high reflectance or a high
      transmittance optical filter, suitable for low bit rate optical communication
      applications with International Telecommunication Union-Telecommunication
      Standardization Sector (ITU-T) standards. We also show the possibility of
      designing an optical filter having a desirable finite reflectance/transmittance
      ratio with simultaneous peaks at ITU-T standard wavelengths. Such filters could
      be suitable for wavelength tuning applications.

PMID- 18830304
TI  - Bound on range precision for shot-noise limited ladar systems.
AB  - The precision of ladar range measurements is limited by noise. The fundamental
      source of noise in a laser signal is the random time between photon arrivals.
      This phenomenon, called shot noise, is modeled as a Poisson random process. Other
      noise sources in the system are also modeled as Poisson processes. Under the
      Poisson-noise assumption, the Cramer-Rao lower bound (CRLB) on range measurements
      is derived. This bound on the variance of any unbiased range estimate is greater
      than the CRLB derived by assuming Gaussian noise of equal variance. Finally, it
      is shown that, for a ladar capable of dividing a fixed amount of energy into
      multiple laser pulses, the range precision is maximized when all energy is
      transmitted in a single pulse.

PMID- 18830305
TI  - Study of a MEMS-based Shack-Hartmann wavefront sensor with adjustable pupil
      sampling for astronomical adaptive optics.
AB  - We introduce a Shack-Hartmann wavefront sensor for adaptive optics that enables
      dynamic control of the spatial sampling of an incoming wavefront using a
      segmented mirror microelectrical mechanical systems (MEMS) device. Unlike a
      conventional lenslet array, subapertures are defined by either segments or groups
      of segments of a mirror array, with the ability to change spatial pupil sampling
      arbitrarily by redefining the segment grouping. Control over the spatial sampling
      of the wavefront allows for the minimization of wavefront reconstruction error
      for different intensities of guide source and different atmospheric conditions,
      which in turn maximizes an adaptive optics system's delivered Strehl ratio.
      Requirements for the MEMS devices needed in this Shack-Hartmann wavefront sensor
      are also presented.

PMID- 18830306
TI  - Piezo-locking a diode laser with saturated absorption spectroscopy.
AB  - We demonstrate modulation-based frequency locking of an external cavity diode
      laser, utilizing a piezo-electrically actuated mirror, external to the laser
      cavity, to create an error signal from saturated absorption spectroscopy. With
      this method, a laser stabilized to a rubidium hyperfine transition has a FWHM of
      130 kHz over seconds, making the locked laser suitable for experiments in atomic
      physics, such as creating and manipulating Bose-Einstein condensates. This
      technique combines the advantages of low-amplitude modulation, simplicity,
      performance, and price, factors that are usually considered to be mutually
      exclusive.

PMID- 18830307
TI  - Analysis of interferograms from a diffractive-lens-based common-path
      interferometer.
AB  - We present a method of numerical analysis of interferograms for a diffractive
      lens-based common-path interferometer recently introduced by Elfstrom et al.
      [Opt. Express 14, 3847 (2006)OPEXFF1094-408710.1364/OE.14.003847]. Practical
      aspects such as the effect of higher diffraction orders upon the interferograms
      are considered. We show that this method can be used to solve the phase function
      of the inspected lens. In addition, we show that by using this method it is
      possible to estimate the focal length and imaging properties of the inspected
      lens.

PMID- 18830308
TI  - Fabrication of a thermally actuated tunable grating and its application as a CO2
      laser beam profile analyzer.
AB  - We propose a thermally actuated tunable grating for measuring the beam profile of
      a CO(2) laser. The grooves of a transmissive grating are filled with a liquid
      whose refractive index depends on temperature. A visible laser as a probe and a
      CO(2) laser as a heat source are illuminated on the grating. The CO(2) laser is
      absorbed, and depending on its beam profile, a temperature profile is induced on
      the grating. The refractive index of the heated liquid is changed, resulting in a
      change of efficiency of the grating for the probe laser. By using the 1st orders
      of diffraction in a 4f imaging system, the beam profile of the CO(2) laser is
      imaged onto a CCD camera by the probe laser.

PMID- 18830309
TI  - Quantitative phase and refractive index analysis of optical fibers using
      differential interference contrast microscopy.
AB  - A systematic and straightforward image processing method to extract quantitative
      phase and refractive index data from weak phase objects is presented, obtained
      using differential interference contrast (DIC) microscopy. The method is
      demonstrated on DIC images of optical fibers where a directional integration
      routine is applied to the DIC images to extract phase and refractive index
      information using the data obtained across the whole DIC image. By applying the
      inverse Abel transform to the resultant phase images, an accurate refractive
      index profile is obtained. The method presented here is compared to the refracted
      near-field technique, typically used to obtain the refractive index profile of
      optical fibers, and shows excellent agreement. It is concluded that through
      careful image processing procedures, DIC microscopy can be successfully
      implemented to obtain quantitative phase and refractive index information of
      optical fibers.

PMID- 18830310
TI  - Photonic crystal fiber for dispersion compensation.
AB  - The dispersion and mode characteristics in a dual-concentric-core photonic
      crystal fiber, based on pure silica, are simulated by the multipole method. The
      fiber exhibits very large negative dispersion due to anticrossing of two
      individual inner core and outer core modes. Near the wavelength of 1.55 microm,
      we could obtain narrowband dispersion-compensating fiber with dispersion values
      of -23,000 ps/km/nm, broadband dispersion-compensating fiber with dispersion
      values from -1000 ps/km/nm to -2500 ps/km/nm over a 200 nm range, and kappa
      values near 300 nm, which matched well with standard single mode fiber. It shows
      that even if there are some changes in the structure parameters during
      fabrication, these fibers can still maintain a fine dispersion-compensating
      property.

PMID- 18830311
TI  - Use of the circular Dammann grating in angle measurement.
AB  - We describe a novel method of angle measurement by borrowing the concept of the
      circular Dammann grating (CDG). A three-order CDG is employed in this experiment.
      The displacement of the tilted angle can be determined accurately by measuring
      the projection from the distorted CDG image. This method is controlled only by
      the initial radius of the image and the converging ratio of the lens. Compared
      with conventional techniques, this technique has the advantages of a simple
      design with superior resolution to within 1 degree, low cost, and compactness. A
      theoretical analysis together with experimental results is presented.

PMID- 18830312
TI  - Phase retrieval of singular scalar light fields using a two-dimensional
      directional wavelet transform and a spatial carrier.
AB  - We evaluate a method based on the two-dimensional directional wavelet transform
      and the introduction of a spatial carrier to retrieve optical phase distributions
      in singular scalar light fields. The performance of the proposed phase-retrieval
      method is compared with an approach based on Fourier transform. The advantages
      and limitations of the proposed method are discussed.

PMID- 18830313
TI  - Estimation of the thickness and the optical parameters of several stacked thin
      films using optimization.
AB  - The reverse engineering problem addressed in the present research consists of
      estimating the thicknesses and the optical constants of two thin films deposited
      on a transparent substrate using only transmittance data through the whole stack.
      No functional dispersion relation assumptions are made on the complex refractive
      index. Instead, minimal physical constraints are employed, as in previous works
      of some of the authors where only one film was considered in the retrieval
      algorithm. To our knowledge this is the first report on the retrieval of the
      optical constants and the thickness of multiple film structures using only
      transmittance data that does not make use of dispersion relations. The same
      methodology may be used if the available data correspond to normal reflectance.
      The software used in this work is freely available through the PUMA Project web
      page (http://www.ime.usp.br/~egbirgin/puma/).

PMID- 18830314
TI  - High-quality frame interpolation in computer generated holographic movies using
      coherent neural networks with a hybrid learning method.
AB  - Computer generated holograms (CGHs) are widely used in optical tweezers, which
      will be employed in various research fields. We previously proposed an efficient
      generation method of CGH movies based on frame interpolation using coherent
      neural networks (CNNs) to reduce the high calculation cost of three-dimensional
      CGHs. At the same time, however, we also found that the quality observed in the
      interpolated CGH images needed to be improved even further so that the method
      could be accepted for general use. We report a successful error reduction in
      interpolated images by developing a new learning method of CNNs. We reduce the
      error by combining locally connected correlation learning and steepest descent
      learning in a sequential manner.

PMID- 18830315
TI  - Signal enhancement of surface plasmon-coupled directional emission by a conical
      mirror.
AB  - A simple strategy for increasing the collection efficiency of surface plasmon
      coupled emission (SPCE) is demonstrated. SPCE is a near-field phenomenon
      occurring when excited fluorophores are in close proximity to a subwavelength
      metal film. The energy of the fluorophores induces surface plasmons that radiate
      the coupled energy at highly specific angles. In an attempt to maximize the
      collected emission, a conical mirror was placed around the coupling prism. The
      result was a nearly 500 fold enhancement over the free space signal as detected
      from a single point from a poly(vinyl alcohol) layer doped with ruthenium.
      Coupling this large enhancement with LED excitation could lead to the development
      of inexpensive, handheld fluorescent devices with high sensitivity.

PMID- 18830316
TI  - Self-imaging of gratings with rough strips.
AB  - We analyze the self-imaging process produced by a transmission grating whose
      strips present two different roughness levels. This kind of grating periodically
      modulates the transmitted light owing only to the different microtopographic
      properties of the strips. In spite of the fact that the grating is not purely
      periodic, it produces a kind of self-image at Talbot distances. These self-images
      gradually appear as light propagates, but they are not present just after the
      grating, as occurs in amplitude or phase gratings. There exists a distance from
      the grating, which depends on the stochastic properties of roughness, from which
      the contrast of the self-images becomes stable. Important cases are analyzed in
      detail, such as low- and high-roughness limits. We assume for the calculations
      that the grating can be used in a mobile system. Simulations using the Rayleigh
      Sommerfeld regime have been performed, which confirm the validity of the
      theoretical approach proposed in this work.

PMID- 18830317
TI  - Calculation of retinal image quality for polychromatic light.
AB  - Although the retinal image is typically polychromatic, few studies have examined
      polychromatic image quality in the human eye. We begin with a conceptual
      framework including the formulation of a psychophysical linking hypothesis that
      underlies the utility of image quality metrics based on the polychromatic point
      spread function. We then outline strategies for computing polychromatic point
      spread functions of the eye when monochromatic aberrations are known for only a
      single wavelength. Implementation problems and solutions for this strategy are
      described. Polychromatic image quality is largely unaffected by wavelength
      dependent diffraction and higher-order chromatic aberration. However, accuracy is
      found to depend critically upon spectral sampling. Using typical aberrations from
      the Indiana Aberration Study, we assessed through-focus image quality for model
      eyes with and without chromatic aberrations using a polychromatic metric called
      the visual Strehl ratio. In the presence of typical levels of monochromatic
      aberrations, the effect of longitudinal chromatic aberration is greatly reduced.
      The effect of typical levels of transverse chromatic aberration is virtually
      eliminated in the presence of longitudinal chromatic aberration and monochromatic
      aberrations. Clinical value and limitations of the method are discussed.

PMID- 18830318
TI  - Propagation of a random electromagnetic beam through a misaligned optical system
      in turbulent atmosphere.
AB  - On the basis of the generalized diffraction integral formula for misaligned
      optical systems in the spatial domain, an analytical propagation expression for
      the elements of the cross-spectral density matrix of a random electromagnetic
      beam passing through a misaligned optical system in turbulent atmosphere is
      derived. Some analyses are illustrated by numerical examples relating to changes
      in the state of polarization of an electromagnetic Gaussian Schell-model beam
      propagating through such an optical system. It is shown that the misalignment has
      a significant influence on the intensity profile and the state of polarization of
      the beam, but the influence becomes smaller for the beam propagating in strong
      turbulent atmosphere. The method in this paper can be applied for sources that
      are either isotropic or anisotropic. It is shown that the isotropic sources and
      the anisotropic sources have different polarization properties on beam
      propagation.

PMID- 18830319
TI  - Modal method for classical diffraction by slanted lamellar gratings.
AB  - We consider lamellar gratings made of dielectric or lossy materials used in
      classical diffraction mounts. We show how the modal diffraction formulation may
      be generalized to deal with slanted lamellar gratings and illustrate the accuracy
      and versatility of the new method through study of highly slanted gratings in a
      homogenization limit. We also comment on the completeness of the eigenmode basis
      and present tests enabling this completeness to be verified numerically.

PMID- 18830320
TI  - Split atmospheric tomography using laser and natural guide stars.
AB  - Laser guide star (LGS) atmospheric tomography is described in the literature as
      integrated minimum-variance tomographic wavefront reconstruction from a
      concatenated wavefront-sensor measurement vector consisting of many high-order,
      tip/tilt (TT)-removed LGS measurements, supplemented by a few low-order natural
      guide star (NGS) components essential to estimating the TT and tilt
      anisoplanatism (TA) modes undetectable by the TT-removed LGS wavefront sensors
      (WFSs). The practical integration of these NGS WFS measurements into the
      tomography problem is the main subject of this paper. A split control
      architecture implementing two separate control loops driven independently by
      closed-loop LGS and NGS measurements is proposed in this context. Its performance
      is evaluated in extensive wave optics Monte Carlo simulations for the Thirty
      Meter Telescope (TMT) LGS multiconjugate adaptive optics (MCAO) system, against
      the delivered performance of the integrated control architecture. Three iterative
      algorithms are analyzed for atmospheric tomography in both cases: a previously
      proposed Fourier domain preconditioned conjugate gradient (FDPCG) algorithm, a
      simple conjugate gradient (CG) algorithm without preconditioning, and a novel
      layer-oriented block Gauss-Seidel conjugate gradient algorithm (BGS-CG). Provided
      that enough iterations are performed, all three algorithms yield essentially
      identical closed-loop residual RMS wavefront errors for both control
      architectures, with the caveat that a somewhat smaller number of iterations are
      required by the CG and BGS-CG algorithms for the split approach. These results
      demonstrate that the split control approach benefits from (i) a simpler
      formulation of minimum-variance atmospheric tomography allowing for algorithms
      with reduced computational complexity and cost (processing requirements), (ii) a
      simpler, more flexible control of the NGS-controlled modes, and (iii) a reduced
      coupling between the LGS- and NGS-controlled modes. Computation and memory
      requirements for all three algorithms are also given for the split control
      approach for the TMT LGS AO system and appear feasible in relation to the
      performance specifications of current hardware technology.

PMID- 18830321
TI  - Deconvolution reconstruction of full-view and limited-view photoacoustic
      tomography: a simulation study.
AB  - Although many algorithms are available for full-view photoacoustic tomography
      (PAT), no exact and stable algorithm for limited-view PAT has been proposed. In
      this paper the deconvolution reconstruction (DR) algorithm is proposed for both
      full-view and limited-view PAT. In the DR algorithm, first a new function is
      constructed from detected photoacoustic signals and approximately simplified, and
      then the tissue's electromagnetic absorption is derived from this function on the
      basis of Fourier-based deconvolution. Computer simulations are carried out to
      compare the DR algorithm with two popular PAT algorithms, the time-domain
      reconstruction (TDR) and the filtered back projection (FBP). Although the error
      of the DR algorithm increases with the size of the detected object, it is shown
      that the DR algorithm has good precision and strong robustness to noise in the
      full-view PAT, nearly equivalent to the TDR and FBP. Yet the DR algorithm is more
      than ten times faster in computation speed. In the limited-view PAT, the DR is
      superior to the TDR and FBP in terms of both accuracy and robustness to noise.

PMID- 18830322
TI  - Evaluation and unification of some methods for estimating reflectance spectra
      from RGB images.
AB  - The problem of estimating spectral reflectances from the responses of a digital
      camera has received considerable attention recently. This problem can be cast as
      a regularized regression problem or as a statistical inversion problem. We
      discuss some previously suggested estimation methods based on critically
      undersampled RGB measurements and describe some relations between them. We
      concentrate mainly on those models that are using a priori information in the
      form of high-resolution measurements. We use the "kernel machine" framework in
      our evaluations and concentrate on the use of multiple illuminations and on the
      investigation of the performance of global and locally adapted estimation
      methods. We also introduce a nonlinear transformation of reflectance values to
      ensure that the estimated reflection spectra fulfill physically motivated
      boundary conditions. The reported experimental results are derived from measured
      and simulated camera responses from the Munsell Matte, NCS, and Pantone data
      sets.

PMID- 18830323
TI  - Coherence effects in digital in-line holographic microscopy.
AB  - We analyze the effects of partial coherence in the image formation of a digital
      in-line holographic microscope (DIHM). The impulse response is described as a
      function of cross-spectral density of the light used in the space-frequency
      domain. Numerical simulation based on the applied model shows that a reduction in
      coherence of light leads to broadening of the impulse response. This is also
      validated by results from experiments wherein a DIHM is used to image latex beads
      using light with different spatial and temporal coherence.

PMID- 18830325
TI  - Effects of the peripheral layers on the optical properties of spherical fish
      lenses.
AB  - We created a computational optical model of spherical fish lenses that takes into
      account the effects of the peripheral layers, which differ in cellular
      composition from the bulk of the lens. A constant refractive index, except for
      the lens capsule, in the outer about 6% of lens radius made it possible to
      uniquely infer the refractive index gradient in more central layers from a known
      or desired longitudinal spherical aberration curve using the inverse Abel
      transform. Since the zone of constant refractive index is wider than necessary to
      make the solution unique and for optimal optical performance of the lens, we
      propose that its width be set by the metabolic needs of the lens.

PMID- 18830326
TI  - Interface between transparent isotropic and uniaxial absorbing dielectric media:
      equations for ray tracing and for the direction of propagation.
AB  - In this work we analyze the propagation of a plane wave that passes from an
      isotropic transparent medium to a uniaxial absorbing medium. Detailed expressions
      that give the real directions of propagation of the wave and the energy of the
      reflected and refracted ordinary and extraordinary waves are obtained. These
      expressions are valid for every orientation of the optic axis of the uniaxial
      medium and for every direction of propagation of the incident wave. Expressions
      are tested in the case of an interface between a transparent and an absorbing
      isotropic media and for the air-rutile (TiO2) interface. The effect of absorption
      has been evaluated by comparing the results obtained in rutile with the results
      obtained in a transparent uniaxial medium with the same real refractive indices.
      Results are presented for different values of the angle of incidence and the
      orientation of the plane of incidence.

PMID- 18830327
TI  - Scattering by a dense finite layer of infinite cylinders at oblique incidence.
AB  - This paper presents the scattering solution for a finite dense layer of cylinders
      irradiated by an arbitrarily polarized plane wave at a general incident
      direction. The theoretical formulation utilizes the effective field approach and
      quasi-crystalline approximation to derive the governing equations for the
      propagation constant and amplitudes of the effective waves. The finite layer
      thickness gives rise to effective waves propagating in both the forward and
      backward directions inside the dense medium. Formulas are developed for the far
      field coherent and incoherent scattered intensities, as well as the extinction
      and scattering cross sections of the dense layer. The forward peak of the
      incoherent scattered intensity is shown to be shifted to the propagating
      direction of the effective waves. The influence of incident direction, layer
      thickness, and solid volume fraction on the scattering properties is illustrated
      by means of a numerical example.

PMID- 18830328
TI  - Renormalization group interpretation of the Born and Rytov approximations.
AB  - In this paper the method of renormalization group (RG) [Phys. Rev. E54, 376
      (1996)] is related to the well-known approximations of Rytov and Born used in
      wave propagation in deterministic and random media. Certain problems in linear
      and nonlinear media are examined from the viewpoint of RG and compared with the
      literature on Born and Rytov approximations. It is found that the Rytov
      approximation forms a special case of the asymptotic expansion generated by the
      RG, and as such it gives a superior approximation to the exact solution compared
      with its Born counterpart. Analogous conclusions are reached for nonlinear
      equations with an intensity-dependent index of refraction where the RG recovers
      the exact solution.

PMID- 18830329
TI  - Determination of height distribution on a rough interface by measuring the
      coherently transmitted or reflected light intensity.
AB  - In this work it is shown theoretically and examined experimentally that the
      measurement of coherently transmitted or reflected monochromatic light intensity
      from a randomly rough interface as a function of incident angle provides the
      height distribution on the interface. It is also shown that the spectrum of
      coherently transmitted or reflected light from a rough interface is modified and
      the modified spectrum yields the height distribution. The experimental results
      obtained by applying both methods, in transmission and reflection, on rough
      surfaces prepared by roughening the sheet glasses by powders of different grain
      sizes are quite consistent. In addition, the effect of the surrounding medium's
      refractive index on the roughness measurement is studied by immersing the samples
      into liquids of different refractive indices. Also, the application range and
      limitations of the introduced methods are discussed.

PMID- 18830330
TI  - Interference in phase space.
AB  - The phase-space representation of interference based on the marginal power
      spectrum gives new insight on interference, enlarging its potential applications
      by means of the principle of spatial coherence modulation. Carrier and (0,pi)
      rays produced by three different types of supports are introduced for describing
      interference as the result of adding the radiant energy propagated by the
      carriers and the modulating energy (which can be positive or negative) propagated
      by the (0,pi)-rays. Numerical examples are presented.

PMID- 18830331
TI  - Generalized signal-to-noise ratio for spectral sensors with correlated bands.
AB  - Traditional spectral sensors are intentionally designed to minimize overlap among
      spectral response functions of different bands. In contrast, some emerging
      classes of spectral sensors exhibit significant band overlap. An effect
      introduced by such band overlap is that the photodetector noise of one band is
      coupled into the others in subsequent data processing steps. Because of this, the
      traditional band-by-band definition of signal-to-noise ratio (SNR) cannot fully
      describe the detector's noise level. We devise a general definition of SNR in
      spectral space based on a recently developed geometrical spectral imaging model
      [J. Opt. Soc. Am. A24, 2864 (2007)]. With this model, we can find an orthogonal
      basis of the spectral response functions for the spectral sensor with decreasing
      instrument SNRs. We can also define the average instrument SNR for the whole
      sensor, which makes it possible to characterize quantitatively the photodetector
      noise of a spectral sensor with correlated bands.

PMID- 18830332
TI  - Multilevel Green's function interpolation method for scattering from composite
      metallic and dielectric objects.
AB  - A multilevel Green's function interpolation method based on two kinds of
      multilevel partitioning schemes--the quasi-2D and the hybrid partitioning scheme-
      is proposed for analyzing electromagnetic scattering from objects comprising both
      conducting and dielectric parts. The problem is formulated using the surface
      integral equation for homogeneous dielectric and conducting bodies. A quasi-2D
      multilevel partitioning scheme is devised to improve the efficiency of the
      Green's function interpolation. In contrast to previous multilevel partitioning
      schemes, noncubic groups are introduced to discretize the whole EM structure in
      this quasi-2D multilevel partitioning scheme. Based on the detailed analysis of
      the dimension of the group in this partitioning scheme, a hybrid quasi-2D/3D
      multilevel partitioning scheme is proposed to effectively handle objects with
      fine local structures. Selection criteria for some key parameters relating to the
      interpolation technique are given. The proposed algorithm is ideal for the
      solution of problems involving objects such as missiles, microstrip antenna
      arrays, photonic bandgap structures, etc. Numerical examples are presented to
      show that CPU time is between O(N) and O(N log N) while the computer memory
      requirement is O(N).

PMID- 18830333
TI  - Recursive T matrix algorithm for resonant multiple scattering: applications to
      localized plasmon excitations.
AB  - A matrix balanced version of the recursive centered T matrix algorithm applicable
      to systems possessing resonant interparticle couplings is presented. Possible
      domains of application include systems containing interacting localized plasmon
      resonances, surface resonances, and photonic jet phenomena. This method is of
      particular interest when considering modifications to complex systems. The
      numerical accuracy of this technique is demonstrated in a study of particles with
      strongly interacting localized plasmon resonances.

PMID- 18830334
TI  - Characterization of near-stoichiometric Ti:LiNbO(3) strip waveguides with varied
      substrate refractive index in the guiding layer.
AB  - We have demonstrated the possibility that near-stoichiometric Ti:LiNbO(3) strip
      waveguides are fabricated by carrying out vapor transport equilibration at 1060
      degrees C for 12 h on a congruent LiNbO(3) substrate with photolithographically
      patterned 4-8 microm wide, 115 nm thick Ti strips. Optical characterizations show
      that these waveguides are single mode at 1.5 microm and show a waveguide loss of
      1.3 dB/cm for TM mode and 1.1 dB/cm for TE mode. In the width/depth direction of
      the waveguide, the mode field follows the Gauss/Hermite-Gauss function. Secondary
      ion-mass spectrometry (SIMS) was used to study Ti-concentration profiles in the
      depth direction and on the surface of the 6 microm wide waveguide. The result
      shows that the Ti profile follows a sum of two error functions along the width
      direction and a complementary error function in the depth direction. The surface
      Ti concentration, 1/e width and depth, and mean diffusivities along the width and
      depth directions of the guide are similar to 3.0 x 10(21) cm(-3), 3.8 microm, 2.6
      microm, 0.30 and 0.14 microm(2)/h, respectively. Micro-Raman analysis was carried
      out on the waveguide endface to characterize the depth profile of Li composition
      in the guiding layer. The results show that the depth profile of Li composition
      also follows a complementary error function with a 1/e depth of 3.64 microm. The
      mean ([Li(Li)]+[Ti(Li)])/([Nb(Nb)]+[Ti(Nb)]) ratio in the waveguide layer is
      about 0.98. The inhomogeneous Li-composition profile results in a varied
      substrate index in the guiding layer. A two-dimensional refractive index profile
      model in the waveguide is proposed by taking into consideration the varied
      substrate index and assuming linearity between Ti-induced index change and Ti
      concentration. The net waveguide surface index increments at 1545 nm are 0.0114
      and 0.0212 for ordinary and extraordinary rays, respectively. Based upon the
      constructed index model, the fundamental mode field profile was calculated using
      the beam propagation method, and the mode sizes and effective index versus the Ti
      strip width were calculated for three lower TM and TE modes using the variational
      method. An agreement between theory and experiment is obtained.

PMID- 18830335
TI  - Monte Carlo modeling of spatial coherence: free-space diffraction.
AB  - We present a Monte Carlo method for propagating partially coherent fields through
      complex deterministic optical systems. A Gaussian copula is used to synthesize a
      random source with an arbitrary spatial coherence function. Physical optics and
      Monte Carlo predictions of the first- and second-order statistics of the field
      are shown for coherent and partially coherent sources for free-space propagation,
      imaging using a binary Fresnel zone plate, and propagation through a limiting
      aperture. Excellent agreement between the physical optics and Monte Carlo
      predictions is demonstrated in all cases. Convergence criteria are presented for
      judging the quality of the Monte Carlo predictions.

PMID- 18830336
TI  - Parametric fuzzy sets for automatic color naming.
AB  - In this paper we present a parametric model for automatic color naming where each
      color category is modeled as a fuzzy set with a parametric membership function.
      The parameters of the functions are estimated in a fitting process using data
      derived from psychophysical experiments. The name assignments obtained by the
      model agree with previous psychophysical experiments, and therefore the high
      level color-naming information provided can be useful for different computer
      vision applications where the use of a parametric model will introduce
      interesting advantages in terms of implementation costs, data representation,
      model analysis, and model updating.

PMID- 18830337
TI  - Focal shift of focused truncated Lorentz-Gauss beam.
AB  - Based on the Collins diffraction integral formula and the complex Gaussian
      expansion of the aperture function, an analytical expression for a Lorentz-Gauss
      beam focused by an optical system with a thin lens and a circular aperture has
      been derived. The focal shift of the focused truncated Lorentz-Gauss beam is
      investigated with numerical examples, and the dependence of the focal shift on
      the different parameters of the focused truncated Lorentz-Gauss beam is discussed
      in detail. This research is useful to the applications of highly divergent laser
      beams.

PMID- 18830338
TI  - Reconstruction of compact binary images from limited Fourier amplitude data.
AB  - The problem of reconstructing a binary image from undersampled Fourier amplitude
      data is considered. This problem maps to an image reconstruction problem in x-ray
      crystallography. The binary constraint is sufficient to overcome the
      undersampling and enforce uniqueness, but is insufficient in the case of the
      additional loss of data that can occur in practice. An iterative projection
      algorithm is developed that uses binary, connectivity, and compactness
      constraints to solve the image reconstruction problem. Simulations show the
      utility of the reconstruction algorithm.

PMID- 18830339
TI  - Introducing secure modes of operation for optical encryption.
AB  - We analyze optical encryption systems using the techniques of conventional
      cryptography. All conventional block encryption algorithms are vulnerable to
      attack, and often they employ secure modes of operation as one way to increase
      security. We introduce the concept of conventional secure modes to optical
      encryption and analyze the results in the context of known conventional and
      optical attacks. We consider only the optical system "double random phase
      encoding," which forms the basis for a large number of optical encryption,
      watermarking, and multiplexing systems. We consider all attacks proposed to date
      in one particular scenario. We analyze only the mathematical algorithms
      themselves and do not consider the additional security that arises from employing
      these algorithms in physical optical systems.

PMID- 18830340
TI  - Ultraviolet upconversion fluorescence from 6D(J) of Gd3+ induced by 980 nm
      excitation.
AB  - Ultraviolet upconversion emissions of 246.2 and 252.8 nm from (6)D(J) levels of
      Gd(3+) ions were observed in GdF(3): 10% Yb(3+), 0.7% Tm(3+) nanocrystals under
      980 nm excitation from a laser diode. The (6)D(J) levels of Gd(3+) ions can be
      efficiently populated by energy transfer processes of Yb-->Tm-->Gd and Yb-->Gd. A
      six-photon upconversion process was confirmed by the dependence of 252.8 nm
      emission intensity on the pumping power. The upconversion mechanism in the six
      photon process was discussed based on excited state absorption of Gd(3+) ions,
      cross relaxation energy transfer between two excited Gd(3+) ions, and energy
      transfer between Gd(3+) and Yb(3+) or Tm(3+) ions.

PMID- 18830341
TI  - Directional emission InP/GaInAsP square-resonator microlasers.
AB  - InP/GaInAsP square-resonator microlasers with an output waveguide connected to
      the midpoint of one side of the square are fabricated by standard
      photolithography and inductively-coupled-plasma etching technique. For a 20-mum
      side square microlaser with a 2-mum-wide output waveguide, cw threshold current
      is 11 mA at room temperature, and the highest mode Q factor is 1.0x10(4) measured
      from the mode linewidth at the injection current of 10 mA. Multimode oscillation
      is observed with the lasing mode wavelength 1546 nm and the side-mode suppression
      ratio of 20 dB at the injection current of 15 mA.

PMID- 18830342
TI  - Power-dependent shaping of vortex solitons in optical lattices with spatially
      modulated nonlinear refractive index.
AB  - We address vortex solitons supported by optical lattices featuring modulation of
      both the linear and nonlinear refractive indices. We find that when the
      modulation is out of phase the competition between both effects results in
      remarkable shape transformations of the solitons that profoundly affect their
      properties and stability. Nonlinear refractive index modulation is found to
      impose restrictions on the maximal power of off-site solitons, which are shown to
      be stable only below a maximum nonlinearity modulation depth.

PMID- 18830343
TI  - Velocity of heat dissipative solitons in optical fibers.
AB  - In the fiber fuse, a pulse of high temperature travels toward the input end of
      the fiber, where high-power laser light is launched into the fiber. At any point
      along the fiber, the soliton can be ignited. The fiber core is damaged in the
      process so that light cannot propagate beyond the hot spot. This phenomenon is an
      example of a dissipative soliton that can exist only in the presence of an
      external energy supply and internal loss. We analyze this phenomenon, derive an
      expression for the velocity of the soliton, and determine its width as functions
      of the physical parameters of the laser and the fiber material.

PMID- 18830344
TI  - Second-order oriented partial-differential equations for denoising in electronic
      speckle-pattern interferometry fringes.
AB  - We derive the second-order oriented partial-differential equations (PDEs) for
      denoising in electronic-speckle-pattern interferometry fringe patterns from two
      points of view. The first is based on variational methods, and the second is
      based on controlling diffusion direction. Our oriented PDE models make the
      diffusion along only the fringe orientation. The main advantage of our filtering
      method, based on oriented PDE models, is that it is very easy to implement
      compared with the published filtering methods along the fringe orientation. We
      demonstrate the performance of our oriented PDE models via application to two
      computer-simulated and experimentally obtained speckle fringes and compare with
      related PDE models.

PMID- 18830345
TI  - Near-infrared luminescence of RbPb2Cl5:Bi crystals.
AB  - A wideband near-IR (NIR) luminescence centered at 1080 nm was found in a
      RbPb(2)Cl(5):Bi single crystal grown by the Bridgman technique. Absorption,
      luminescence, and excitation of luminescence spectra were investigated at room
      and cryogenic temperatures. The luminescence was proposed to be due to the
      (3)P(1)-->(3)P(0) transition in Bi(+) ion.

PMID- 18830346
TI  - Wide temperature range operation of micrometer-scale silicon electro-optic
      modulators.
AB  - We demonstrate high bit rate electro-optic modulation in a resonant micrometer
      scale silicon modulator over an ambient temperature range of 15 K. We show that
      low bit error rates can be achieved by varying the bias current through the
      device to thermally counteract the ambient temperature changes. Robustness in the
      presence of thermal variations can enable a wide variety of applications for
      dense on chip electronic photonic integration.

PMID- 18830347
TI  - High-power laser diodes emitting light above 1100 nm with a small vertical
      divergence angle of 13 degrees.
AB  - Laser diodes with highly strained InGaAs quantum wells, emitting at 1130 nm,
      embedded in a GaAs waveguide were investigated. This Letter reviews the design of
      the vertical structure for enclosing high output power in angles smaller than 18
      degrees . Example designs were processed to 200 microm stripe-width lasers with
      an 8-mm-long optical cavity. When these are mounted on C mounts, they give an
      output power of 38 W under quasi-cw operation from a single emitter.

PMID- 18830348
TI  - Observation of time correlation function of multimode two-photon pairs on a
      rubidium D2 line.
AB  - We report on the generation of a type-I multimode two-photon state on a rubidium
      D(2) line (780 nm) using periodically poled KTiOPO(4) crystals. With a degenerate
      optical parametric oscillator far below threshold, we observe an oscillatory
      correlation function; the cross correlation between two photons shows a cavity
      bandwidth of about 7.8 MHz. We also use a Fabry-Perot etalon to filter its most
      longitudinal modes and observe its time correlation function. The experimental
      data are well fitted to theoretical curves. This system could be utilized for
      demonstrating storage and retrieval of narrow-band photons in Rb atomic
      ensembles, which is important for long-distance quantum communication.

PMID- 18830349
TI  - Spectroscopy and femtosecond laser performance of Yb3+:YAlO3 crystal.
AB  - We report what we believe to be the first demonstration of cw and passively mode
      locked Yb(3+):YAlO(3) (Yb:YAP) laser operation under diode pumping. Spectroscopic
      properties of a 0.6 at.%Yb(3+)-doped YAP single crystal were investigated. Output
      power up to 1.2 W with slope efficiency of 64.5% in the cw regime and 225 fs
      pulse duration with average power of 0.8 W from a mode-locked Yb:YAP laser were
      demonstrated.

PMID- 18830350
TI  - Quantum electrodynamics analysis of optical binding in counterpropagating beams
      and effect of particle size.
AB  - A general expression for optical binding energy between particles of any size, in
      counterpropagating beams with and without interference, is derived using quantum
      electrodynamics. The effect of particle size on the optically induced
      interparticle energy surface, which has been the subject of recent research, is
      explored. Significant changes in this surface when particle size approaches the
      wavelength of the optical field are revealed. Finally, optically induced particle
      arrays that may be fabricated with these potentials are briefly discussed.

PMID- 18830351
TI  - Tunable photonic Bloch oscillations in electrically modulated photonic crystals.
AB  - We exploit theoretically the occurrence and tunability of photonic Bloch
      oscillations (PBOs) in one-dimensional photonic crystals (PCs) containing
      nonlinear composites. Because of the enhanced third-order nonlinearity (Kerr-type
      nonlinearity) of composites, photons undergo oscillations inside tilted photonic
      bands, which are achieved by the application of graded external-pump electric
      fields on such PCs, varying along the direction perpendicular to the surface of
      layers. The tunability of PBOs (including amplitude and period) is readily
      achieved by changing the field gradient. With an appropriate graded pump ac or dc
      electric field, terahertz PBOs can appear and cover a terahertz band in an
      electromagnetic spectrum.

PMID- 18830352
TI  - Investigation of gain ripple in two-pump fiber optical parametric amplifiers.
AB  - By using the four-sideband theory, we analyze the gain spectrum in wideband two
      pump fiber optical parametric amplifiers and predict gain ripples over the flat
      gain region. We derive an approximation of their pseudo-periods and discuss
      methods for reducing their amplitudes.

PMID- 18830353
TI  - High-Q microfluidic cavities in silicon-based two-dimensional photonic crystal
      structures.
AB  - We demonstrate postprocessed microfluidic double-heterostructure cavities in
      silicon-based photonic crystal slab waveguides. The cavity structure is realized
      by selective fluid infiltration of air holes using a glass microtip, resulting in
      a local change of the average refractive index of the photonic crystal. The
      microcavities are probed by evanescent coupling from a silica nanowire. An
      intrinsic quality factor of 57,000 has been derived from our measurements,
      representing what we believe to be the largest value observed in microfluidic
      photonic crystal cavities to date.

PMID- 18830354
TI  - Measurement of subcellular texture by optical Gabor-like filtering with a digital
      micromirror device.
AB  - We demonstrate an optical Fourier processing method to quantify object texture
      arising from subcellular feature orientation within unstained living cells. Using
      a digital micromirror device as a Fourier spatial filter, we measured cellular
      responses to two-dimensional optical Gabor-like filters optimized to sense
      orientation of nonspherical particles, such as mitochondria, with a width around
      0.45 microm. Our method showed significantly rounder structures within apoptosis
      defective cells lacking the proapoptotic mitochondrial effectors Bax and Bak,
      when compared with Bax/Bak expressing cells functional for apoptosis, consistent
      with reported differences in mitochondrial shape in these cells. By decoupling
      spatial frequency resolution from image resolution, this method enables rapid
      analysis of nonspherical submicrometer scatterers in an undersampled large field
      of view and yields spatially localized morphometric parameters that improve the
      quantitative assessment of biological function.

PMID- 18830355
TI  - Spontaneous emission of quantum dot excitons into surface plasmons in a nanowire.
AB  - The spontaneous emission (SE) of quantum dot (QD) excitons into surface plasmons
      in a cylindrical nanowire is investigated theoretically. Maxwell's equations with
      appropriate boundary conditions are solved numerically to obtain the dispersion
      relations of surface plasmons. The SE rate of QD excitons is found to be greatly
      enhanced at certain values of the exciton bandgap. Application in generation of
      remote entangled states via superradiance is also pointed out and may be
      observable with current technology.

PMID- 18830356
TI  - Electrically tunable Sagnac filter based on a photonic bandgap fiber with liquid
      crystal infused.
AB  - We demonstrate an electrically tunable Sagnac filter based on a photonic bandgap
      fiber that is realized by infusing liquid crystal into a solid-core air-hole
      photonic crystal fiber. The filter enables an electrical tuning with a range of
      about 26 nm for one single interference minimum in the transmission bandgap from
      1330 to 1650 nm wavelength. The tuning efficiency is averaged to 0.53 nm/V.

PMID- 18830357
TI  - Optimization of the dimensions of an Yb(3+):ZBLANP optical fiber sample for laser
      cooling of solids.
AB  - We propose a theoretical model for an optimized fiber structure for use in anti
      Stokes laser cooling of solids. The sample is an optical fiber fabricated from a
      fluorozirconate glass ZBLANP with a core doped with Yb(3+) ions. The diameter of
      the fiber core is optimized to achieve the largest temperature change in the
      sample. It is shown that for each value of the pump power there is an optimized
      diameter of the fiber core, which permits the largest drop in the temperature of
      the sample.

PMID- 18830358
TI  - High-repetition-rate, 491 MHz, femtosecond fiber laser with low timing jitter.
AB  - We demonstrate a soliton fiber laser based on an anomalously dispersive erbium
      doped fiber butt-coupled to a saturable absorber mirror for passive mode locking.
      The laser generates 180 fs pulses at a repetition rate of 491 MHz and exhibits a
      timing jitter as low as 20 fs over the frequency range 1 kHz-10 MHz.

PMID- 18830359
TI  - Biomimetic subwavelength antireflective gratings on GaAs.
AB  - We have developed a simple and scalable bottom-up approach for fabricating moth
      eye antireflective coatings on GaAs substrates. Monolayer, non-close-packed
      silica colloidal crystals are created on crystalline GaAs wafers by a spin
      coating-based single-layer reduction technique. These colloidal monolayers can be
      used as etching masks during a BCl(3) dry-etch process to generate subwavelength
      structured antireflective gratings directly on GaAs substrates. The gratings
      exhibit excellent broadband antireflective properties, and the specular
      reflection matches with the theoretical prediction using a rigorous coupled-wave
      analysis model. These bioinspired antireflection coatings have important
      technological applications ranging from efficient solar cells to IR detectors.

PMID- 18830360
TI  - Bi-doped fiber lasers and amplifiers for a spectral region of 1300-1470 nm.
AB  - Bismuth-doped fiber lasers operating in the range 1300-1470 nm have been
      demonstrated for the first time, to our knowledge. It has been shown that Bi
      doped alumina-free phosphogermanosilicate fibers reveal optical gain in a
      wavelength range of 1240-1485 nm with pumping at 1205, 1230, or 808 nm.

PMID- 18830361
TI  - High-speed photonically assisted analog-to-digital conversion using a continuous
      wave multiwavelength source and phase modulation.
AB  - A more simple photonically assisted analog-to-digital conversion system utilizing
      a cw multiwavelength source and phase modulation instead of a mode-locked laser
      is presented. The output of the cw multiwavelength source is launched into a
      dispersive device (such as a single-mode fiber). This fiber creates a pulse
      train, where the central wavelength of each pulse corresponds to a spectral line
      of the optical source. The pulses can then be either dispersed again to perform
      discrete wavelength time stretching or demultiplexed for continuous time analog
      to-digital conversion. We experimentally demonstrate the operation of both time
      stretched and interleaved systems at 38 GHz. The potential of integrating this
      type of system on a monolithic chip is discussed.

PMID- 18830362
TI  - Transient functional blood flow change in the human brain measured noninvasively
      by diffusing-wave spectroscopy.
AB  - Multispeckle diffusing-wave spectroscopy (DWS) is used to measure blood flow
      transients in the human visual cortex following stimulation by 7.5 Hz full-field
      and checkerboard flickering. The average decay time tau(d) characterizing the
      decay of the DWS autocorrelation function shows a biphasic behavior; within about
      2 s after stimulation onset, tau(d) increases rapidly to about 6% above the
      baseline value. At later times, tau(d) slowly decreases and reaches a steady
      state value about 5% below the baseline value after about 15 s. The initial
      increase of the DWS signal suggests a transient reduction of the cortical blood
      flow velocity shortly after stimulation onset. Measurements of this transient
      response at different positions over the primary visual cortex show a spatial
      pattern different from the one measured by electroencephalography.

PMID- 18830363
TI  - Ultrahigh-frame-rate nitric oxide planar laser-induced fluorescence imaging.
AB  - We demonstrate the ability to generate ultrahigh frequency burst sequences of
      deep UV at 226 nm by mixing the optical parametric oscillator signal output at
      622 nm with third harmonic at 355 nm from a pulse burst laser system. We obtained
      226 nm burst sequences with uniform burst envelopes, and the average pulse energy
      is approximately 0.5 mJ. Nitric oxide planar laser-induced fluorescence image
      sequences at ultrahigh (100 kHz) frame rates have been obtained.

PMID- 18830364
TI  - Guard-band influence on orthogonal-band-multiplexed coherent optical OFDM.
AB  - Coherent optical orthogonal frequency-division multiplexing (OFDM) has recently
      been demonstrated beyond 100 Gb/s using orthogonal band multiplexing (OBM). OBM
      OFDM gives a multitude of benefits in implementing high-speed optical OFDM
      transmission. We investigate the system sensitivity to the guard band of OBM
      OFDM. The result suggests that when the guard band equals a multiple of the
      subcarrier spacing, the Q penalty practically vanishes. We also show that two
      OFDM bands can be demodulated simultaneously with one fast Fourier transform,
      owing to interband orthogonality, and its performance is almost the same as one
      band detection.

PMID- 18830365
TI  - Controllable propagation of light pulses in Er-doped fibers with saturable
      absorption.
AB  - We report controllable (slow or fast) propagation of low-intensity probe-light
      pulses through erbium-doped fiber periodically saturated by the synchronized
      master-pulse sequence. These two pulse sequences could have significantly
      different carrier wavelengths within the fundamental absorption spectrum 1470
      1570 nm of Er(+3) ions. The effect of fractional delay or advancement grew with
      the fiber optical absorption at the probe wavelength and could be significantly
      stronger than that at the saturating wavelength. The probe-pulse advancement was
      observed in the case when the saturating and probe waves were modulated
      approximately in antiphase. The observed effects are explained in the framework
      of a simple model of a periodically saturated homogeneously broadened absorption
      line.

PMID- 18830366
TI  - Prevention of decoherence by two femtosecond chirped pulse trains.
AB  - We study the vibrational energy relaxation (VER) and collisional dephasing as
      channels of coherence loss in a vibrational mode that is selectively excited
      using chirped pulse adiabatic passage in the Raman configuration. Based on the
      dressed state picture analysis we propose a method to reduce decoherence using
      femtosecond chirped pulse trains. When applied with a period close to the VER
      time, the pulse trains allow one to sustain high coherence in the selected
      vibrational mode.

PMID- 18830367
TI  - Diode end-pumped high-power Q-switched double Nd:YAG slab laser and its efficient
      near-field second-harmonic generation.
AB  - We reported on an all-solid-state double Nd:YAG slab laser. The laser was based
      on two diode end-pumped Nd:YAG slabs and a stable-unstable hybrid resonator. A cw
      output of 189 W and an average Q-switched output of 169 W at 10 kHz with an M(2)
      factor of 1.5 in the slow direction and 1.7 in the fast direction were obtained.
      We demonstrated efficient near-field frequency doubling by imaging the one
      dimensional top-hat near-field to a lithium triborate frequency doubler. We
      obtained 93 W green light at 10 kHz with a pulse width of 10.7 ns. The efficiency
      of second-harmonic generation was up to 57%.

PMID- 18830368
TI  - Symmetry breaking in honeycomb photonic lattices.
AB  - We study the phenomena associated with symmetry breaking in honeycomb photonic
      lattices. As the honeycomb structure is gradually deformed, conical diffraction
      around its diabolic points becomes elliptic and eventually no longer occurs. As
      the deformation is further increased, a gap opens between the first two bands,
      and the lattice can support a gap soliton. The existence of the gap soliton
      serves as a means to detect the symmetry breaking and provide an estimate of the
      size of the gap.

PMID- 18830369
TI  - Ultrahigh-repetition-rate bound-soliton harmonic passive mode-locked fiber
      lasers.
AB  - On the basis of numerical simulation results, we put forward a way to realize
      harmonic passive mode locking of fiber lasers with an ultrahigh-repetition-rate
      pulse train. The equidistant distribution of ultrashort pulses filling the total
      laser cavity is due to bound-soliton mechanisms. In the case of large bound
      energy, such long soliton trains are very stable and have the ideal periodic
      structure as a soliton crystal.

PMID- 18830371
TI  - Electromagnetic surface waves of multilayer stacks: coupling between guided modes
      and Bloch modes.
AB  - The study of the dependence of surface mode dispersion on the termination of
      multilayer stacks reveals interesting features. For stratified media with high
      refractive-index contrasts, surface modes can shift across several bandgaps if
      the thickness of the final layer is changed. The distance to the photonic band
      edge influences the decay length of the mode inside the multilayer stack. In the
      middle of the bandgap, the electromagnetic energy is concentrated in the final
      layer of the crystal, while near bandgap edges the decay length extends over
      several periods. Additional evidence suggests that surface modes behave like
      guided modes that can couple with the extended Bloch modes and give rise to
      evanescent field profiles oscillating along several periods.

PMID- 18830370
TI  - Time-resolved single-photon detection by femtosecond upconversion.
AB  - We demonstrate a time-resolved single-photon detection technique based on
      ultrafast sum-frequency generation, providing femtosecond measurement capability
      for single photons in photonic quantum information processing. Noncollinear
      broadband upconversion in periodically poled MgO-doped stoichiometric lithium
      tantalate with an ultrafast pump and detection with a Si single-photon counter
      enable efficient detection of IR photons and temporal resolution of ~150 fs. We
      utilize the timing resolution to map the generation efficiency profile along the
      propagation axis of a periodically poled KTiOPO(4) crystal, revealing its local
      grating quality with millimeter resolution. We also apply the technique to two
      photon coincidence measurements and directly demonstrate time anticorrelation
      between coincident-frequency entangled photons that are parametrically generated
      under extended phase-matching conditions.

PMID- 18830372
TI  - Visualizing of skin chromophore concentrations by use of RGB images.
AB  - A method is proposed for visualizing simply the concentrations of melanin,
      oxygenated blood, and deoxygenated blood in skin tissue using digital RGB images.
      The total blood concentration and oxygen saturation can also be reconstructed.
      Monte Carlo simulation of light transport specifies a relation between the
      chromophore concentrations and Commission Internationale de l'Eclairage XYZ,
      which are compatible with the common RGB working space. Experiments with a
      tissuelike agar gel phantom demonstrated the possibility of the method. In vivo
      imaging of a human hand during forearm occlusion demonstrated the ability of the
      method to evaluate hemodynamics of skin tissue.

PMID- 18830373
TI  - Evolution of the degree of polarization of an electromagnetic Gaussian Schell
      model beam in a Gaussian cavity.
AB  - The interaction of an electromagnetic Gaussian Schell-model (EGSM) beam with a
      Gaussian cavity is analyzed. In particular, the evolution of the degree of
      polarization of the EGSM beam is investigated. The results show that the behavior
      of the degree of polarization depends on both the statistical properties of the
      source that generates the EGSM beam and the parameters of the cavity.

PMID- 18830374
TI  - Far-field detection of the dipole vortex.
AB  - The energy flow lines (field lines of the Poynting vector) of electric dipole
      radiation exhibit a vortex structure in the near field when the dipole moment of
      the source is in circular rotation. The spatial extend of this vortex is smaller
      than a wavelength and may not be observable by a measurement in the near field.
      We show that the rotation of the field lines close to the source affects the
      image of the dipole in the far field, and this opens the possibility for
      observation of this vortex by a measurement in the far field.

PMID- 18830375
TI  - Optical coherence refractometry.
AB  - We introduce a novel approach to refractometry using a low coherence
      interferometer at multiple angles of incidence. We show that for plane parallel
      samples it is possible to measure their phase refractive index rather than the
      group index that is usually measured by interferometric methods. This is a
      significant development because it enables bulk refractive index measurement of
      scattering and soft samples, not relying on surface measurements that can be
      prone to error. Our technique is also noncontact and compatible with in situ
      refractive index measurements. Here, we demonstrate this new technique on a pure
      silica test piece and a highly scattering resin slab, comparing the results with
      standard critical angle refractometry.

PMID- 18830376
TI  - Materials with on-demand refractive indices in the terahertz range.
AB  - We demonstrate the possibility to create materials with chosen refractive indices
      and a strong birefringence in the terahertz range by etching of patterns with
      appropriate filling factors in a dielectric substrate. We show that by using deep
      inductive plasma etching of silicon wafers, it is possible to achieve a
      birefringence as high as 1.2 in an 80 microm thick layer. The resulting stacks
      were used as building blocks for a photonic crystal displaying sharp defect mode
      peaks in transmittance.

PMID- 18830377
TI  - Single higher-order transverse mode operation of a radially polarized Nd:YAG
      laser using an annularly reflectivity-modulated photonic crystal coupler.
AB  - We demonstrate single higher-order transverse mode operation of a radially
      polarized Nd:YAG laser by using a polarization-selective and reflectivity
      modulated output coupler. A narrow annular region with low reflectivity
      fabricated in a photonic crystal mirror behaves so as to select a higher-order
      transverse mode of a cylindrically symmetric laser beam. A double-ring-shaped
      radially polarized TM(02) mode beam is stably generated.

PMID- 18830378
TI  - Electro-optic integration of embedded electrodes and waveguides in LiNbO3 using a
      femtosecond laser.
AB  - We describe the fabrication of a Mach-Zehnder optical modulator in LiNbO(3) by
      femtosecond laser micromachining, which is composed of optical waveguides
      inscripted by a femtosecond laser and embedded microelectrodes subsequently
      fabricated using femtosecond laser ablation and selective electroless plating. A
      half-wave voltage close to 19 V is achieved at a wavelength of 632.8 nm with an
      interaction length of 2.6 mm. This simple and cost-effective technique opens up
      new opportunities for fabricating integrated electro-optic devices.

PMID- 18830379
TI  - Correlation of macrophage inflammatory protein-2 expression and brain edema in
      rats after intracerebral hemorrhage.
AB  - Brain edema is one of the most frequent and serious complications of
      intracerebral hemorrhage (ICH), but its underlying mechanism remains largely
      unknown. In order to understand whether inflammatory mediators released from the
      blood after cerebral hemorrhage plays a role in brain edema, we investigated the
      dynamic change of the inflammatory mediator macrophage inflammatory protein-2
      (MIP-2) in rat brain after ICH. Our results indicate that the expression of MIP-2
      increases 2 hours and peaks 2 days after ICH. The expression of MIP-2 correlates
      with NF-kappaB activation and brain water content. These results suggest that MIP
      2 expression may play an important role in the development of brain edema after
      ICH in rats.

PMID- 18830381
TI  - Reversibility of aberrant global DNA and estrogen receptor-alpha gene methylation
      distinguishes colorectal precancer from cancer.
AB  - Alterations in the global methylation of DNA and in specific regulatory genes are
      two epigenetic alterations found in cancer. However, the significance of
      epigenetic changes for diagnosis and/or prognosis of colorectal cancer have not
      been established, although it has been extensively investigated. Recently we have
      identified a new type of cancer cell called precancerous stem cells (pCSCs) and
      proposed that cancer may arise from a lengthy development process of tumor
      initiating cells (TICs) --> pCSCs --> cancer stem cells (CSCs) --> cancer, which
      is in parallel to histological changes of hyperplasia (TICs) --> precancer
      (pCSCs) --> carcinoma (CSCs/cancer cells), accompanied by clonal evolutionary
      epigenetic and genetic alterations. In this study, we investigated whether
      aberrant DNA methylation can be used as a biomarker for the differentiation
      between premalignant and malignant lesions in the colorectum. The profile of
      global DNA and estrogen receptor (ER)-alpha gene methylation during cancer
      development was determined by analysis of 5-methylcytosine (5-MeC) using
      immunohistochemical (IHC) staining, dot blot analysis or a quantitative gene
      methylation assay (QGMA). Herein we show that global DNA hypomethylation and ER
      alpha gene hypermethylation are progressively enhanced from hyperplastic polyps
      (HPs) --> adenomatous polyps (APs) --> adenomatous carcinoma (AdCa). The aberrant
      methylation can be completely reversed in APs, but not in AdCa by a nonsteroidal
      anti-inflammatory drug (NSAID) celecoxib, which is a selective inhibitor of
      cyclooxygenase-2 (Cox-2), suggesting that the epigenetic alterations between
      colorectal precancer (AP) and cancer (AdCa) are fundamentally different in
      response to anti-cancer therapy. In normal colorectal mucosa, while global DNA
      methylation was not affected by aging, ER-alpha gene methylation was
      significantly increased with aging. However, this increase did not reach the
      level observed in colorectal APs. Taken together, reversibility of aberrant
      global DNA and ER-alpha gene methylation distinguishes colorectal precancer from
      cancer.

PMID- 18830383
TI  - Small lymphocytic lymphoma/chronic lymphocytic leukemia in a pelvic myelolipoma.
AB  - Myelolipoma is a rare benign tumor composed of mature adipose tissue and normal
      hematopoietic elements. Extra-adrenal myelolipomas are extremely rare, with
      approximately 50% of cases occurring in the presacral region. We report a case of
      an 85 year old woman who presented with small bowel obstruction relating to a
      pelvic mass detected on computed tomography (CT) scan. At laparotomy, a 12-cm.
      pre-sacral mass was resected. Histologic examination showed a myelolipoma with
      dense lymphoid aggregates. On immunostains, the lymphoid aggregates showed
      positivity for CD20, CD5, and CD23, consistent with small lymphocytic
      lymphoma/chronic lymphocytic leukemia (SLL/CLL). Molecular evaluation confirmed
      the presence of a clonal B-cell lymphocytic proliferation that did not harbor BCL
      2 or BCL-1 gene rearrangements. This case represents the first report of a
      myelolipoma involved by a non-Hodgkin lymphoma. The unique combination of these
      findings raises questions about the relationship between the two observed
      entities. The likeliest scenario is that an unusual benign tumor (myelolipoma)
      was colonized by a relatively common systemic hematopoietic neoplasm SLL/CLL,
      producing a collision tumor.

PMID- 18830382
TI  - Hypothesis: hemolytic transfusion reactions represent an alternative type of
      anaphylaxis.
AB  - Classical anaphylaxis is the most severe, and potentially fatal, type of allergic
      reaction, manifested by hypotension, bronchoconstriction, and vascular
      permeability. Similarly, a hemolytic transfusion reaction (HTR) is the most
      feared consequence of blood transfusion. Evidence for the existence of an
      alternative, IgG-mediated pathway of anaphylaxis may be relevant for explaining
      the pathophysiology of IgG-mediated-HTRs. The purpose of this review is to
      summarize the evidence for this alternative pathway of anaphylaxis and to present
      the hypothesis that an IgG-mediated HTR is one example of this type of
      anaphylaxis.

PMID- 18830380
TI  - Infection and cervical neoplasia: facts and fiction.
AB  - Whilst there is strong evidence that human papillomavirus (HPV) is the principal
      aetiological agent in cervical neoplasia, some other sexually transmitted agents
      may either contribute or protect against cervical carcinogenesis, such as the
      herpes virus family (HSV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), human
      immunodeficiency virus (HIV) or Chlamydia trachomatis (CT). Epidemiological
      studies suggest that HSV may have a role in cervical neoplasia, but there is no
      clear supportive experimental evidence. Serological studies have also failed to
      reveal a difference in the prevalence of antibodies to CMV and EBV between
      patients with cervical cancer and controls. However, longitudinal
      seroepidemiological studies have provided evidence that CT is an independent risk
      factor for the development of cervical squamous carcinoma and this association is
      serotype specific. The increased risk of cervical neoplasia in patients infected
      with HIV has been recognised for over a decade and HIV may interact with HPV
      either by alternating HPV gene transcription or by immunosuppression. Finally
      extensive experimental and limited epidemiological evidence suggests that adeno
      associated viruses (AAV) may have antioncogenic activity in man and may protect
      against the development of cervical cancer. At present the mechanism of this
      action is unclear but may relate to AAV-induced regulation of HPV gene expression
      and the HPV life cycle. In this review we summarize the current literature
      relating to the associations and mechanisms of cervical carcinogenesis by each of
      these infectious microorganisms.

PMID- 18830384
TI  - Metastatic prostatic carcinoma to testis: histological features mimicking
      lymphoma.
AB  - We report a case of prostatic carcinoma with testicular metastasis, which
      mimicked malignant lymphoma of the testis. The patient was a 71 year-old man with
      a history of prostate adenocarcinoma of Gleason score 9 (4+5) diagnosed in 2001
      for which he received hormonal therapy. Four years later, the patient developed
      multiple osteoblastic bone metastases. Radiotherapy of the bone metastases was
      given with subsequently bilateral orchiectomy for hormonal deprivation therapy in
      May 2005. Grossly, one of the testes had a subcapsular rubbery 0.9 cm nodule.
      Microscopically, the nodule was composed of malignant discohesive cells
      predominantly infiltrating in the interstitium with an appearance of malignant
      lymphoma. However, immunohistochemical stains were positive for prostate-specific
      antigen and prostate acid phosphatase and negative for leukocyte common antigen,
      which confirmed the diagnosis of metastatic prostate adenocarcinoma.

PMID- 18830385
TI  - Diagnostic and prognostic biomarkers in pancreatic carcinoma.
AB  - Pancreatic ductal carcinoma, one of the leading causes of cancer mortality, is
      typically diagnosed at an advanced stage, which significantly contributes to its
      high mortality rates. Studies have demonstrated that resection of small
      pancreatic tumors and tumors at lower stages correlates with improved survival.
      Detection of pancreatic carcinoma at an early, surgically resectable stage is the
      key to decreasing mortality and improving survival. Identification of sensitive
      diagnostic biomarkers as screening tools is crucial in detecting preinvasive
      pancreatic neoplasms. Numerous new DNA-, RNA- and protein-based biomarkers have
      been extensively investigated. This review aims to provide an update on these
      molecular markers, including biomarkers from blood, tissue as well as pancreatic
      juice and cystic fluid. These biomarkers hold potential utility in early
      diagnosis and prognostification of pancreatic ductal carcinoma, though many of
      which need to be validated in large-scale prospective studies before they can be
      used in clinical settings.

PMID- 18830386
TI  - Multicentric infarcted leiomyoadenomatoid tumor: a case report.
AB  - Adenomatoid tumor is a benign, usually small lesion that may be found within the
      wall of fallopian tubes or beneath the uterine serosa near the uterine cornu. It
      is often accompanied by smooth muscle hypertrophy that may obscure the
      adenomatoid tumor. We herein report a very unusual case of infarcted
      leiomyoadenomatoid tumor of the uterus and ovary in a 24-year-old woman who
      presented with severe lower abdominal pain and masses in the uterus and right
      ovary. Pelvic ultrasonography and computed tomography revealed a 5 cm mass in the
      myometrium and a 4 cm mass in the right ovary. Laparoscopy-assisted transvaginal
      mass removal was performed under the clinical impression of a uterine leiomyoma
      and benign ovarian teratoma. On a microscopic examination, prominent fascicles of
      smooth muscle separated or infiltrated by cuboidal or signet ring-like vacuolated
      cells, as well as tubular formations lined by flattened mesothelial cells and
      extensive necrosis were observed in both masses. The microscopic appearance often
      suggested the possibility of a malignant neoplasm due to irregular
      pseudoinfiltration with atypical cuboidal cells and the paucity of a typical
      adenomatoid tumor due to infarction, and the presence of epithelial-appearing
      cells in the hypertrophic smooth muscle bundles that mimicked an infiltrating
      carcinoma for a leiomyoma or myometrium. These unemphasized features of
      leiomyoadenomatoid tumors may potentially lead to more aggressive therapy than
      warranted if not correctly interpreted, especially for infarcted cases.

PMID- 18830387
TI  - Decreased survival and hepato-renal pathology in mice with C-terminally truncated
      GP73 (GOLPH2).
AB  - GP73 (Golph2) is a type II Golgi-localized integral membrane protein that is
      normally expressed in epithelial cells of many human tissues, and that is highly
      upregulated in liver disease. While its function is unknown, the GP73 C-terminus
      contains putative protein-interaction domains. We used a gene trap approach to
      generate mice with a severe truncation of the GP73 C-terminus (GP73(tr/tr)) in
      order to investigate the physiological role of this protein. GP73(tr/tr) mice
      were born at the expected rate and were fertile, but cumulative survival was
      significantly reduced compared to wild-type controls, particularly in females.
      GP73(tr/tr) mice developed varying degrees of renal disease, most notably focal
      segmental glomerulosclerosis and hyaline thrombi. In addition to renal
      abnormalities, GP73(tr/tr) mice developed marked microvesicular hepatic
      steatosis, hepatocyte nuclear membrane irregularities and intranuclear
      inclusions. GP73(tr/tr) expression in morphologically normal kidneys and livers
      was constitutively low, but was strikingly upregulated in the diseased kidney
      cortex, and was upregulated in livers in animals of advanced age. Despite the
      substantial morphological changes in the kidneys and liver, routine screening
      serum assays provided no evidence of renal or hepatic dysfunction. Consequently,
      the cause of the increased mortality of GP73(tr/tr) animals is unclear at
      present. Our study indicates that GP73 is essential for normal survival, and
      suggests multiple roles for GP73 in epithelial cell function in the kidney and
      liver.

PMID- 18830388
TI  - Antralization of the gastric mucosa of the incisura angularis and its gastrin
      expression.
AB  - The frequency of antrum-type mucosa and gastrin expression in gastric biopsies
      from the incisura angularis was assessed in 60 consecutive patients having
      gastrointestinal symptoms. Following the recommendations from the updated Sydney
      System for the classification and grading of gastritis, two biopsies were taken
      from the antrum, one from the incisura and two from the corpus. Sections were
      stained with H&E, Giemsa and for gastrin. Gastrin-positive cells were semi
      quantified as: 0 (none), </= 9, 10- 49 cells and >/=50 gastrin-labelled cells/40x
      field. Antrum-type mucosa at the incisura (called antralization) occurred in 30%
      of the biopsies without inflammation, but in 69% of those with H. pylori-induced
      gastritis, and in 64% of those with autoimmune gastritis. At the incisura,
      gastrin-labelled cells (>/=10) were found in 62% (18/29) of biopsies showing
      antralization, but in only 20% (3/15) of those having transitional-type mucosa
      (p<0.05) and in none of the 16 biopsies having fundic-type mucosa. The similarity
      in gastrin expression between the mucosa of the gastric antrum and the antral
      type mucosa at the incisura substantiates the notion that antralization is a
      metaplastic transformation. The significantly higher frequency of antral-type
      mucosa at the incisura in patients with gastritis than in those without gastritis
      strongly suggests that chronic inflammation per se triggers antralization of the
      incisura, irrespective of the presence or absence of H. pylori infection.

PMID- 18830389
TI  - Endocervicosis of the bladder: report of a case and review of the current
      literature.
AB  - An important variety of metaplastic lesions of the urinary bladder have been
      reported in the medical literature up to date. Among those of Mullerian origin,
      endocervicosis is the most infrequent. We report a 67 years old woman who
      presented with a history of left flank pain and dysuria for the past 2 months.
      Imaging studies revealed a solid mass in the posterior bladder wall protruding
      into the lumen. Transurethral resection of the lesion was performed. Both
      pathologic examination and immunohistochemistry confirmed the diagnosis of
      endocervicosis. The patient was monitored with 6 months interval follow up and
      remains disease free 12 months post surgery.

PMID- 18830390
TI  - Pitfalls in diagnostic hematopathology: part I.
AB  - Pitfalls in diagnostic hematopathology are underestimated and underreported.
      Major causes of diagnostic error in hematopathology include: 1) inadequate
      material; 2) inadequate workup; 3) inadequate clinical correlation; 4) over or
      under interpretation; 5) challenges in hematopathology. In the first part of this
      review series, I will focus on the pitfalls in diagnosing and differentiating
      chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and mantle cell
      lymphoma, and discuss the strategies to avoid potential diagnostic errors based
      on my personal experience.

PMID- 18830392
TI  - Cost-effectiveness analysis for trigeminal neuralgia: Cyberknife vs microvascular
      decompression.
AB  - BACKGROUND/AIMS: We present the preliminary results of a cost-effectiveness
      analysis of cyberknife radiosurgery (CKR) versus microvascular decompression
      (MVD) for patients with medically unresponsive trigeminal neuralgia. METHODS:
      Direct healthcare costs from hospital's perspective attributable to CKR and MVD
      were collected. Pain level caused by trigeminal neuralgia was measured through
      the Barrow Neurological Institute pain intensity scoring criteria, at admission
      and after an average of 6 months follow-up. RESULTS: 20 patients for both arms
      were enrolled, for a total of 40 patients. The two procedures resulted equally
      effective at 6 month follow-up, with different resources consumption: CKR
      reducing hospital costs by an average of 34% per patient. The robustness of these
      results was confirmed in appropriate sensitivity analyses. CONCLUSION: CKR
      resulted to be a cost-saving alternative compared with the surgical intervention.

PMID- 18830393
TI  - Behavior and neuropsychiatric manifestations in Angelman syndrome.
AB  - Angelman syndrome has been suggested as a disease model of neurogenetic
      developmental condition with a specific behavioral phenotype. It is due to lack
      of expression of the UBE3A gene, an imprinted gene located on chromosome 15q.
      Here we review the main features of this phenotype, characterized by happy
      demeanor with prominent smiling, poorly specific laughing and general exuberance,
      associated with hypermotor behavior, stereotypies, and reduced behavioral
      adaptive skills despite proactive social contact. All these phenotypic
      characteristics are currently difficult to quantify and have been subject to some
      differences in interpretation. For example, prevalence of autistic disorder is
      still debated. Many of these features may occur in other syndromic or
      nonsyndromic forms of severe intellectual disability, but their combination, with
      particularly prominent laughter and smiling may be specific of Angelman syndrome.
      Management of problematic behaviors is primarily based on behavioral approaches,
      though psychoactive medication (eg, neuroleptics or antidepressants) may be
      required.

PMID- 18830394
TI  - Assessment of anxiety and depression after lower limb amputation in Jordanian
      patients.
AB  - OBJECTIVE: This study aimed to assess the prevalence of anxiety and depression
      among Jordanian lower limb amputees with different clinical characteristics and
      sociodemographic data (gender, marital status, social support, income, type and
      level of amputation, and occupation). METHODS: Participants were 56 patients with
      unilateral lower limb amputation with mean duration (8.4 +/- 5.75 years). They
      were recruited from inpatient and outpatient clinics of Jordan University
      hospital, Royal Farah Rehabilitation Center, and Al-basheer hospital in Amman,
      Jordan. Participants responded to a questionnaire that included a battery of
      questions requesting brief information about sociodemographic variables and
      characteristics of amputation. The level of depression and anxiety in each
      participating patient was assessed by the Hospital Anxiety and Depression Scale
      (HADS). RESULTS: The prevalence of anxiety and depressive symptoms were 37% and
      20%, respectively. Factors associated with high prevalence of psychological
      symptoms included female gender, lack of social support, unemployment, traumatic
      amputation, shorter time since amputation, and amputation below the knee. These
      findings were confirmed by a significant reduction of anxiety and depression
      scores in patients who received social support, patients with amputation due to
      disease, and patients with amputation above the knee. Presence of pain and use of
      prosthesis had no effect on the prevalence. CONCLUSIONS: The findings of the
      present study highlight the high incidence of psychiatric disability and
      depression in amputees; it also showed the importance of sociodemographic factors
      in psychological adjustment to amputation. It is suggested that psychiatric
      evaluation and adequate rehabilitation should form a part of their overall
      management.

PMID- 18830391
TI  - Strategies for molecular imaging dementia and neurodegenerative diseases.
AB  - Dementia represents a heterogeneous term that has evolved to describe the
      behavioral syndromes associated with a variety of clinical and neuropathological
      changes during continuing degenerative disease of the brain. As such, there lacks
      a clear consensus regarding the neuropsychological and other constituent
      characteristics associated with various cerebrovascular changes in this disease
      process. But increasing this knowledge has given more insights into memory
      deterioration in patients suffering from Alzheimer's disease and other subtypes
      of dementia. The author reviews current knowledge of the physiological coupling
      between cerebral blood flow and metabolism in the light of state-of-the-art
      imaging methods and its changes in dementia with special reference to Alzheimer's
      disease. Different imaging techniques are discussed with respect to their
      visualizing effect of biochemical, cellular, and/or structural changes in
      dementia. The pathophysiology of dementia in advanced age is becoming
      increasingly understood by revealing the underlying basis of neuropsychological
      changes with current imaging techniques, genetic and pathological features, which
      suggests that alterations of (neuro) vascular regulatory mechanisms may lead to
      brain dysfunction and disease. The current view is that cerebrovascular
      deregulation is seen as a contributor to cerebrovascular pathologies, such as
      stroke, but also to neurodegenerative conditions, such as Alzheimer's disease.
      The better understanding of these (patho) physiological mechanisms may open an
      approach to new interventional strategies in dementia to enhance neurovascular
      repair and to protect neurovascular coupling.

PMID- 18830395
TI  - Disruption of bradycardia associated with discriminative conditioning in combat
      veterans with PTSD.
AB  - The effects of combat-related posttraumatic stress disorder (PTSD) on heart rate
      (HR) responding associated with a discriminative delay eyeblink (EB) conditioning
      paradigm are reported. Combat PTSD+, Combat PTSD-, and Noncombat PTSD- veterans
      were assessed with psychometric self-report measures, and baseline heart rate
      variability (HRV) was measured before receiving a 72-trial session of
      discriminative EB classical conditioning. Two types (red or green light) of
      conditioned stimuli (CS) were used: one (CS+) predicted a tone, followed
      immediately by an aversive stimulus (corneal airpuff); the other (CS-) predicted
      a tone alone, not followed by the airpuff. The light signal was presented for 5
      seconds, during which HR was measured. On all psychometric measures, the PTSD+
      subgroup was significantly different from the PTSD- subgroups (Combat +
      Noncombat), and the PTSD- subgroups did not significantly differ from each other.
      A linear deceleration in HR to CS+ and CS- signals was found in the combined PTSD
      subgroup and on CS- trials in the PTSD+ subgroup, but was not present on CS+
      trials in the PTSD+ subgroup. Results are interpreted with respect to a
      behavioral stages model of conditioned bradycardia and in terms of neural
      substrates which are both critical to HR conditioning and known to be abnormal in
      PTSD.

PMID- 18830396
TI  - Dissociative identity disorder and prepulse inhibition of the acoustic startle
      reflex.
AB  - A group of persons with dissociative identity disorder (DID) was compared with a
      group of persons with other dissociative disorders, and a group of nondiagnosed
      controls with regard to prepulse inhibition (PPI) of the acoustic startle reflex.
      The findings suggest maladaptive attentional processes at a controlled level, but
      not at a preattentive automatic level, in persons with DID. The prepulse occupied
      more controlled attentional resources in the DID group compared with the other
      two groups. Preattentive automatic processing, on the other hand, was normal in
      the DID group. Moreover, startle reflexes did not habituate in the DID group. In
      conclusion, increased PPI and delayed habituation is consistent with increased
      vigilance in individuals with DID. The present findings of reduced habituation of
      startle reflexes and increased PPI in persons with DID suggest the operation of a
      voluntary process that directs attention away from unpleasant or threatening
      stimuli. Aberrant voluntary attentional processes may thus be a defining
      characteristic in DID.

PMID- 18830397
TI  - The framework for disturbed affective consciousness in autism.
AB  - The current article explores the implication of the interaction of emotion and
      consciousness for autism. The framework that is proposed for the disorder
      explains that the compromised functional integrity of the amygdala is the root
      cause of disturbed affective consciousness. Amygdala, with its connections to
      various cortical and subcortical regions, helps detect a fearful facial
      expression at the attentional periphery and make it the focus of attention and
      awareness for enhanced processing. The conscious life of autistics with respect
      to affective objects can thus be very different from that of normal people, which
      leads them to perceive the world differently. They process fearful stimuli the
      way normal controls perceive common objects by activating areas responsible for
      feature based analysis rather than the amygdala and other connected areas.
      Conscious perception of such stimuli is important for appropriate development of
      emotion concepts, something that autistics lack, thus leading to impairment in
      the awareness of one's own emotions especially within the negative spectrum with
      a prominent position for fearful stimuli. Thus the interaction of emotion with
      consciousness is ripe for investigation and can help to throw light on the mental
      life of autistics.

PMID- 18830399
TI  - New treatment options for fibromyalgia: critical appraisal of duloxetine.
AB  - Fibromyalgia syndrome (FMS) is a chronic condition characterized by widespread
      pain, tender points, fatigue, and sleep disturbance. FMS leads to high disability
      levels, poor quality of life, and extensive use of medical care. Effective
      pharmacological treatment options are rare, and treatment effects are often of
      limited duration. Duloxetine is a new selective serotonin and norepinephrine
      reuptake inhibitor that is licensed for the treatment of pain in diabetic
      neuropathy. So far two randomized, placebo-controlled trials have investigated
      the short-term safety and efficacy of duloxetine 60 mg/day and 120 mg/day in
      patients suffering from FMS over a period of 12 weeks. Both dosages were superior
      to placebo in pain relief, and improvement in quality of life and depressive
      symptoms. The analgesic effect was largely independent of the antidepressant
      action of duloxetine. The higher dose of 120 mg/day further reduced the tender
      point count and elevated the tender point pain thresholds. Only mild to moderate
      adverse effects were reported. Duloxetine 60 mg/day and 120 mg/day has proven to
      be beneficial in the treatment of FMS symptoms. As true for other antidepressants
      further studies are needed to assess the long-term efficacy and safety of
      duloxetine as an additional pharmacological treatment option in FMS.

PMID- 18830398
TI  - Zebrafish: An in vivo model for the study of neurological diseases.
AB  - As the population ages, there is a growing need for effective therapies for the
      treatment of neurological diseases. A limited number of therapeutics are
      currently available to improve cognitive function and research is limited by the
      need for in vivo models. Zebrafish have recently become a focus of
      neurobehavioral studies since larvae display neuropathological and behavioral
      phenotypes that are quantifiable and relate to those seen in man. Due to the
      small size of Zebrafish larvae, assays can be undertaken in 96 well plates and as
      the larvae can live in as little as 200 mul of fluid, only a few milligrams of
      compound are needed for screening. Thus in vivo analysis of the effects of
      compounds can be undertaken at much earlier stages in the drug discovery process.
      This review will look at the utility of the zebrafish in the study of
      neurological diseases and its role in improving the throughput of candidate
      compounds in in vivo screens.

PMID- 18830400
TI  - Management of migraine in adolescents.
AB  - Headaches in children and adolescents are still under-diagnosed. 75% of children
      are affected by primary headache by the age of 15 with 28% fitting the ICHD2
      criteria of migraine. Migraine is considered a chronic disorder that can severely
      impact a child's daily activities, including schooling and socializing. Early
      recognition and aggressive therapy, with acute and prophylactic treatments, as
      well as intensive biobehavioral interventions, are essential to control the
      migraine attacks and reverse the progression into intractable disabling headache.

PMID- 18830401
TI  - Neuropsychological effects and attitudes in patients following electroconvulsive
      therapy.
AB  - The current study examined the effects of electroconvulsive therapy (ECT) on
      neuropsychological test performance. Forty-six patients completed brief
      neuropsychological and psychological testing before and after receiving ECT for
      the treatment of recalcitrant and severe depression. Neuropsychological testing
      consisted of the Levin Selective Reminding Test (Levin) and Wechsler Memory Scale
      Revised Edition (WMS-R). Self-report measures included the Beck Depression
      Inventory (BDI), the Short-Term Memory Questionnaire (STMQ), and several other
      measures of emotional functioning and patient attitudes toward ECT. The mean
      number of days between pre-ECT and post-ECT testing was 24. T-test revealed a
      significant decrease in subjective ratings of depression as rated by the BDI,
      t(45) = 9.82, P < 0.0001 (Pre-BDI = 27.9 +/- 20.2; post-BDI = 13.5 +/- 9.7).
      Objective ratings of memory appeared impaired following treatment, and patients'
      self-report measures of memory confirmed this decline. More specifically,
      repeated measures MANOVA [Wilks Lambda F(11,30) = 4.3, p < 0.001] indicated
      significant decreases for measures of immediate recognition memory (p < 0.005),
      long-term storage (p < 0.05), delayed prose passage recall (p < 0.0001), percent
      retained of prose passages (p < 0.0001), and percent retained of visual designs
      (p < 0.0001). In addition, the number of double mentions on the Levin increased
      (p < 0.02). This study suggests that there may be a greater need to discuss the
      intermittent cognitive risks associated with ECT when obtaining informed consent
      prior to treatment. Further that self-reports of cognitive difficulties may
      persist even when depression has remitted. However, patients may not acknowledge
      or be aware of changes in their memory functioning, and post-ECT self-reports may
      not be reliable.

PMID- 18830402
TI  - Chemical addressability of ultraviolet-inactivated viral nanoparticles (VNPs).
AB  - BACKGROUND: Cowpea Mosaic Virus (CPMV) is increasingly being used as a
      nanoparticle platform for multivalent display of molecules via chemical
      bioconjugation to the capsid surface. A growing variety of applications have
      employed the CPMV multivalent display technology including nanoblock chemistry,
      in vivo imaging, and materials science. CPMV nanoparticles can be inexpensively
      produced from experimentally infected cowpea plants at high yields and are
      extremely stable. Although CPMV has not been shown to replicate in mammalian
      cells, uptake in mammalian cells does occur in vitro and in vivo. Thus,
      inactivation of the virus RNA genome is important for biosafety considerations,
      however the surface characteristics and chemical reactivity of the particles must
      be maintained in order to preserve chemical and structural functionality.
      METHODOLOGY/PRINCIPAL FINDINGS: Short wave (254 nm) UV irradiation was used to
      crosslink the RNA genome within intact particles. Lower doses of UV previously
      reported to inactivate CPMV infectivity inhibited symptoms on inoculated leaves
      but did not prohibit systemic virus spread in plants, whereas higher doses caused
      aggregation of the particles and an increase in chemical reactivity further
      indicating broken particles. Intermediate doses of 2.0-2.5 J/cm(2) were shown to
      maintain particle structure and chemical reactivity, and cellular binding
      properties were similar to CPMV-WT. CONCLUSIONS: These studies demonstrate that
      it is possible to inactivate CPMV infectivity while maintaining particle
      structure and function, thus paving the way for further development of CPMV
      nanoparticles for in vivo applications.

PMID- 18830403
TI  - Amerindian Helicobacter pylori strains go extinct, as european strains expand
      their host range.
AB  - We studied the diversity of bacteria and host in the H. pylori-human model. The
      human indigenous bacterium H. pylori diverged along with humans, into African,
      European, Asian and Amerindian groups. Of these, Amerindians have the least
      genetic diversity. Since niche diversity widens the sets of resources for
      colonizing species, we predicted that the Amerindian H. pylori strains would be
      the least diverse. We analyzed the multilocus sequence (7 housekeeping genes) of
      131 strains: 19 cultured from Africans, 36 from Spanish, 11 from Koreans, 43 from
      Amerindians and 22 from South American Mestizos. We found that all strains that
      had been cultured from Africans were African strains (hpAfrica1), all from
      Spanish were European (hpEurope) and all from Koreans were hspEAsia but that
      Amerindians and Mestizos carried mixed strains: hspAmerind and hpEurope strains
      had been cultured from Amerindians and hpEurope and hpAfrica1 were cultured from
      Mestizos. The least genetically diverse H. pylori strains were hspAmerind.
      Strains hpEurope were the most diverse and showed remarkable multilocus sequence
      mosaicism (indicating recombination). The lower genetic structure in hpEurope
      strains is consistent with colonization of a diversity of hosts. If diversity is
      important for the success of H. pylori, then the low diversity of Amerindian
      strains might be linked to their apparent tendency to disappear. This suggests
      that Amerindian strains may lack the needed diversity to survive the diversity
      brought by non-Amerindian hosts.

PMID- 18830404
TI  - Meltrin beta/ADAM19 interacting with EphA4 in developing neural cells
      participates in formation of the neuromuscular junction.
AB  - BACKGROUND: Development of the neuromuscular junction (NMJ) is initiated by the
      formation of postsynaptic specializations in the central zones of muscles,
      followed by the arrival of motor nerve terminals opposite the postsynaptic
      regions. The post- and presynaptic components are then stabilized and modified to
      form mature synapses. Roles of ADAM (A Disintegrin And Metalloprotease) family
      proteins in the formation of the NMJ have not been reported previously. PRINCIPAL
      FINDINGS: We report here that Meltrin beta, ADAM19, participates in the formation
      of the NMJ. The zone of acetylcholine receptor alpha mRNA distribution was
      broader and excess sprouting of motor nerve terminals was more prominent in
      meltrin beta-deficient than in wild-type embryonic diaphragms. A microarray
      analysis revealed that the preferential distribution of ephrin-A5 mRNA in the
      synaptic region of muscles was aberrant in the meltrin beta-deficient muscles.
      Excess sprouting of motor nerve terminals was also found in ephrin-A5 knockout
      mice, which lead us to investigate a possible link between Meltrin beta and
      ephrin-A5-Eph signaling in the development of the NMJ. Meltrin beta and EphA4
      interacted with each other in developing motor neurons, and both of these
      proteins localized in the NMJ. Coexpression of Meltrin beta and EphA4 strongly
      blocked vesicular internalization of ephrin-A5-EphA4 complexes without requiring
      the protease activity of Meltrin beta, suggesting a regulatory role of Meltrin
      beta in ephrin-A5-Eph signaling. CONCLUSION: Meltrin beta plays a regulatory role
      in formation of the NMJ. The endocytosis of ephrin-Eph complexes is required for
      efficient contact-dependent repulsion between ephrin and Eph. We propose that
      Meltrin beta stabilizes the interaction between ephrin-A5 and EphA4 by regulating
      endocytosis of the ephrinA5-EphA complex negatively, which would contribute to
      the fine-tuning of the NMJ during development.

PMID- 18830405
TI  - Cerebrospinal fluid dendritic cells infiltrate the brain parenchyma and target
      the cervical lymph nodes under neuroinflammatory conditions.
AB  - BACKGROUND: In many neuroinflammatory diseases, dendritic cells (DCs) accumulate
      in several compartments of the central nervous system (CNS), including the
      cerebrospinal fluid (CSF). Myeloid DCs invading the inflamed CNS are thus thought
      to play a major role in the initiation and perpetuation of CNS-targeted
      autoimmune responses. We previously reported that, in normal rats, DCs injected
      intra-CSF migrated outside the CNS and reached the B-cell zone of cervical lymph
      nodes. However, there is yet no information on the migratory behavior of CSF
      circulating DCs under neuroinflammatory conditions. METHODOLOGY/PRINCIPAL
      FINDINGS: To address this issue, we performed in vivo transfer experiments in
      rats suffering from experimental autoimmune encephalomyelitis (EAE), a model of
      multiple sclerosis. EAE or control rats were injected intra-CSF with bone marrow
      derived myeloid DCs labeled with the fluorescent marker carboxyfluorescein
      diacetate succinimidyl ester (CFSE). In parallel experiments, fluorescent
      microspheres were injected intra-CSF to EAE rats in order to track endogenous
      antigen-presenting cells (APCs). Animals were then sacrificed on day 1 or 8 post
      injection and their brain and peripheral lymph nodes were assessed for the
      presence of microspheres(+) APCs or CFSE(+) DCs by immunohistology and/or FACS
      analysis. Data showed that in EAE rats, DCs injected intra-CSF substantially
      infiltrated several compartments of the inflamed CNS, including the
      periventricular demyelinating lesions. We also found that in EAE rats, as
      compared to controls, a larger number of intra-CSF injected DCs reached the
      cervical lymph nodes. This migratory behavior was accompanied by an accentuation
      of EAE clinical signs and an increased systemic antibody response against myelin
      oligodendrocyte glycoprotein, a major immunogenic myelin antigen.
      CONCLUSIONS/SIGNIFICANCE: Altogether, these results indicate that CSF-circulating
      DCs are able to both survey the inflamed brain and to reach the cervical lymph
      nodes. In EAE and maybe multiple sclerosis, CSF-circulating DCs may thus support
      the immune responses that develop within and outside the inflamed CNS.

PMID- 18830406
TI  - Egr-1 regulates autophagy in cigarette smoke-induced chronic obstructive
      pulmonary disease.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a progressive lung
      disease characterized by abnormal cellular responses to cigarette smoke,
      resulting in tissue destruction and airflow limitation. Autophagy is a
      degradative process involving lysosomal turnover of cellular components, though
      its role in human diseases remains unclear. METHODOLOGY AND PRINCIPAL FINDINGS:
      Increased autophagy was observed in lung tissue from COPD patients, as indicated
      by electron microscopic analysis, as well as by increased activation of
      autophagic proteins (microtubule-associated protein-1 light chain-3B, LC3B, Atg4,
      Atg5/12, Atg7). Cigarette smoke extract (CSE) is an established model for
      studying the effects of cigarette smoke exposure in vitro. In human pulmonary
      epithelial cells, exposure to CSE or histone deacetylase (HDAC) inhibitor rapidly
      induced autophagy. CSE decreased HDAC activity, resulting in increased binding of
      early growth response-1 (Egr-1) and E2F factors to the autophagy gene LC3B
      promoter, and increased LC3B expression. Knockdown of E2F-4 or Egr-1 inhibited
      CSE-induced LC3B expression. Knockdown of Egr-1 also inhibited the expression of
      Atg4B, a critical factor for LC3B conversion. Inhibition of autophagy by LC3B
      knockdown protected epithelial cells from CSE-induced apoptosis. Egr-1(-/-) mice,
      which displayed basal airspace enlargement, resisted cigarette-smoke induced
      autophagy, apoptosis, and emphysema. CONCLUSIONS: We demonstrate a critical role
      for Egr-1 in promoting autophagy and apoptosis in response to cigarette smoke
      exposure in vitro and in vivo. The induction of autophagy at early stages of COPD
      progression suggests novel therapeutic targets for the treatment of cigarette
      smoke induced lung injury.

PMID- 18830407
TI  - Telomerase deficiency affects the formation of chromosomal translocations by
      homologous recombination in Saccharomyces cerevisiae.
AB  - Telomerase is a ribonucleoprotein complex required for the replication and
      protection of telomeric DNA in eukaryotes. Cells lacking telomerase undergo a
      progressive loss of telomeric DNA that results in loss of viability and a
      concomitant increase in genome instability. We have used budding yeast to
      investigate the relationship between telomerase deficiency and the generation of
      chromosomal translocations, a common characteristic of cancer cells. Telomerase
      deficiency increased the rate of formation of spontaneous translocations by
      homologous recombination involving telomere proximal sequences during crisis.
      However, telomerase deficiency also decreased the frequency of translocation
      formation following multiple HO-endonuclease catalyzed DNA double-strand breaks
      at telomere proximal or distal sequences before, during and after crisis. This
      decrease correlated with a sequestration of the central homologous recombination
      factor, Rad52, to telomeres determined by chromatin immuno-precipitation. This
      suggests that telomerase deficiency results in the sequestration of Rad52 to
      telomeres, limiting the capacity of the cell to repair double-strand breaks
      throughout the genome. Increased spontaneous translocation formation in
      telomerase-deficient yeast cells undergoing crisis is consistent with the
      increased incidence of cancer in elderly humans, as the majority of our cells
      lack telomerase. Decreased translocation formation by recombinational repair of
      double-strand breaks in telomerase-deficient yeast suggests that the reemergence
      of telomerase expression observed in many human tumors may further stimulate
      genome rearrangement. Thus, telomerase may exert a substantial effect on global
      genome stability, which may bear significantly on the appearance and progression
      of cancer in humans.

PMID- 18830408
TI  - Robust intrapulmonary CD8 T cell responses and protection with an attenuated N1L
      deleted vaccinia virus.
AB  - BACKGROUND: Vaccinia viruses have been used as a model for viral disease and as a
      protective live vaccine. METHODOLOGY AND PRINCIPAL FINDINGS: We investigated the
      immunogenicity of an attenuated strain of vaccinia virus engineered to inactivate
      the N1L gene (vGK5). Using the intranasal route, this recombinant virus was 2
      logs less virulent compared to the wildtype VACV-WR. Infection by the intranasal,
      intraperitoneal, and tail scarification routes resulted in the robust induction
      of cytolytic virus-specific CD8 T cells in the spleens and the lungs. VACV
      specific antibodies were also detected in the sera of mice infected 3-5 months
      prior with the attenuated vGK5 virus. Finally, mice immunized with vGK5 were
      significantly protected when challenged with a lethal dose of VACV-WR.
      CONCLUSIONS: These results indicate that the attenuated vGK5 virus protects
      against subsequent infection and suggest that the N1L protein limits the strength
      of the early antiviral CD8 T cell response following respiratory infection.

PMID- 18830409
TI  - Non-opsonic phagocytosis of Legionella pneumophila by macrophages is mediated by
      phosphatidylinositol 3-kinase.
AB  - BACKGROUND: Legionella pneumophila, is an intracellular pathogen that causes
      Legionnaires' disease in humans, a potentially lethal pneumonia. L. pneumophila
      has the ability to enter and replicate in the host and is essential for
      pathogenesis. METHODOLOGY/PRINCIPAL FINDINGS: Phagocytosis was measured by cell
      invasion assays. Construction of PI3K mutant by PCR cloning and expression of
      dominant negative mutant was detected by Western blot. PI3K activity was measured
      by 32P labeling and detection of phospholipids products by thin layer
      chromatography. Infection of macrophages with virulent L. pneumophila stimulated
      the formation of phosphatidylinositol 3-phosphate (PIP3), a phosphorylated lipid
      product of PI3K whereas two structurally distinct phosphatidylinositol 3 kinase
      (PI3K) inhibitors, wortmannin and LY294002, reduced L. pneumophila entry into
      macrophages in a dose-dependent fashion. Furthermore, PI3K activation led to Akt
      stimulation, a serine/threonine kinase, which was also inhibited by wortmannin
      and LY294002. In contrast, PI3K and protein kinase B (PKB/Akt) activities were
      lower in macrophages infected with an avirulent bacterial strain. Only virulent
      L. pneumophila increased lipid kinase activity present in immunoprecipitates of
      the p85alpha subunit of class I PI3K and tyrosine phosphorylated proteins. In
      addition, macrophages expressing a specific dominant negative mutant of PI3K
      reduced L. pneumophila entry into these cells. CONCLUSION/SIGNIFICANCE: Entry of
      L. pneumophila is mediated by PI3K/Akt signaling pathway. These results suggest
      an important role for PI3K and Akt in the L. pneumophila infection process. They
      point to possible novel strategies for undermining L. pneumophila host uptake and
      reducing pathogenesis of Legionnaires' disease.

PMID- 18830410
TI  - Evolution of the aging brain transcriptome and synaptic regulation.
AB  - Alzheimer's disease and other neurodegenerative disorders of aging are
      characterized by clinical and pathological features that are relatively specific
      to humans. To obtain greater insight into how brain aging has evolved, we
      compared age-related gene expression changes in the cortex of humans, rhesus
      macaques, and mice on a genome-wide scale. A small subset of gene expression
      changes are conserved in all three species, including robust age-dependent
      upregulation of the neuroprotective gene apolipoprotein D (APOD) and
      downregulation of the synaptic cAMP signaling gene calcium/calmodulin-dependent
      protein kinase IV (CAMK4). However, analysis of gene ontology and cell type
      localization shows that humans and rhesus macaques have diverged from mice due to
      a dramatic increase in age-dependent repression of neuronal genes. Many of these
      age-regulated neuronal genes are associated with synaptic function. Notably,
      genes associated with GABA-ergic inhibitory function are robustly age
      downregulated in humans but not in mice at the level of both mRNA and protein.
      Gene downregulation was not associated with overall neuronal or synaptic loss.
      Thus, repression of neuronal gene expression is a prominent and recently evolved
      feature of brain aging in humans and rhesus macaques that may alter neural
      networks and contribute to age-related cognitive changes.

PMID- 18830411
TI  - AA-amyloidosis can be transferred by peripheral blood monocytes.
AB  - Spongiform encephalopathies have been reported to be transmitted by blood
      transfusion even prior to the clinical onset. Experimental AA-amyloidosis shows
      similarities with prion disease and amyloid-containing organ-extracts can prime a
      recipient for the disease. In this systemic form of amyloidosis N-terminal
      fragments of the acute-phase reactant apolipoprotein serum amyloid A are the main
      amyloid protein. Initial amyloid deposits appear in the perifollicular region of
      the spleen, followed by deposits in the liver. We used the established murine
      model and induced AA-amyloidosis in NMRI mice by intravenous injections of
      purified amyloid fibrils ('amyloid enhancing factor') combined with inflammatory
      challenge (silver nitrate subcutaneously). Blood plasma and peripheral blood
      monocytes were isolated, sonicated and re-injected into new recipients followed
      by an inflammatory challenge during a three week period. When the animals were
      sacrificed presence of amyloid was analyzed in spleen sections after Congo red
      staining. Our result shows that some of the peripheral blood monocytes, isolated
      from animals with detectable amyloid, contained amyloid-seed that primed for AA
      amyloid. The seeding material seems to have been phagocytosed by the cells since
      the AA-precursor (SAA1) was found not be expressed by the monocytes. Plasma
      recovered from mice with AA amyloidosis lacked seeding capacity. Amyloid
      enhancing activity can reside in monocytes recovered from mice with AA
      amyloidosis and in a prion-like way trigger amyloid formation in conjunction with
      an inflammatory disorder. Human AA-amyloidosis resembles the murine form and
      every individual is expected to be exposed to conditions that initiate production
      of the acute-phase reactant. The monocyte-transfer mechanism should be eligible
      for the human disease and we point out blood transfusion as a putative route for
      transfer of amyloidosis.

PMID- 18830413
TI  - Obesity makes for a big headline.

PMID- 18830414
TI  - PTEN posttranslational inactivation and hyperactivation of the PI3K/Akt pathway
      sustain primary T cell leukemia viability.
AB  - Mutations in the phosphatase and tensin homolog (PTEN) gene leading to PTEN
      protein deletion and subsequent activation of the PI3K/Akt signaling pathway are
      common in cancer. Here we show that PTEN inactivation in human T cell acute
      lymphoblastic leukemia (T-ALL) cells is not always synonymous with PTEN gene
      lesions and diminished protein expression. Samples taken from patients with T-ALL
      at the time of diagnosis very frequently showed constitutive hyperactivation of
      the PI3K/Akt pathway. In contrast to immortalized cell lines, most primary T-ALL
      cells did not harbor PTEN gene alterations, displayed normal PTEN mRNA levels,
      and expressed higher PTEN protein levels than normal T cell precursors. However,
      PTEN overexpression was associated with decreased PTEN lipid phosphatase
      activity, resulting from casein kinase 2 (CK2) overexpression and
      hyperactivation. In addition, T-ALL cells had constitutively high levels of ROS,
      which can also downmodulate PTEN activity. Accordingly, both CK2 inhibitors and
      ROS scavengers restored PTEN activity and impaired PI3K/Akt signaling in T-ALL
      cells. Strikingly, inhibition of PI3K and/or CK2 promoted T-ALL cell death
      without affecting normal T cell precursors. Overall, our data indicate that T-ALL
      cells inactivate PTEN mostly in a nondeletional, posttranslational manner.
      Pharmacological manipulation of these mechanisms may open new avenues for T-ALL
      treatment.

PMID- 18830415
TI  - Maintenance of cardiac energy metabolism by histone deacetylase 3 in mice.
AB  - Histone deacetylase (HDAC) inhibitors show remarkable therapeutic potential for a
      variety of disorders, including cancer, neurological disease, and cardiac
      hypertrophy. However, the specific HDAC isoforms that mediate their actions are
      unclear, as are the physiological and pathological functions of individual HDACs
      in vivo. To explore the role of Hdac3 in the heart, we generated mice with a
      conditional Hdac3 null allele. Although global deletion of Hdac3 resulted in
      lethality by E9.5, mice with a cardiac-specific deletion of Hdac3 survived until
      3-4 months of age. At this time, they showed massive cardiac hypertrophy and
      upregulation of genes associated with fatty acid uptake, fatty acid oxidation,
      and electron transport/oxidative phosphorylation accompanied by fatty acid
      induced myocardial lipid accumulation and elevated triglyceride levels. These
      abnormalities in cardiac metabolism can be attributed to excessive activity of
      the nuclear receptor PPARalpha. The phenotype associated with cardiac-specific
      Hdac3 gene deletion differs from that of all other Hdac gene mutations. These
      findings reveal a unique role for Hdac3 in maintenance of cardiac function and
      regulation of myocardial energy metabolism.

PMID- 18830416
TI  - CD4+CD25+ Tregs control the TRAIL-dependent cytotoxicity of tumor-infiltrating
      DCs in rodent models of colon cancer.
AB  - Tumors that progress do so via their ability to escape the antitumor immune
      response through several mechanisms, including developing ways to induce the
      differentiation and/or recruitment of CD4(+)CD25(+) Tregs. The Tregs, in turn,
      inhibit the cytotoxic function of T cells and NK cells, but whether they have an
      effect on the cytotoxic function of tumor-infiltrating DCs (TIDCs) has not been
      determined. Here we have shown, in 2 rodent models of colon cancer, that
      CD4(+)CD25(+) Tregs inhibit the ability of CD11b(+) TIDCs to mediate TNF-related
      apoptosis-inducing ligand-induced (TRAIL-induced) tumor cell death. In both
      models of cancer, combination treatment with Mycobacterium bovis Bacillus
      Calmette-Guerin (BCG), which activates the innate immune system via TLR2, TLR4,
      and TLR9, and cyclophosphamide (CTX), which depletes Tregs, eradicated the
      tumors. Further analysis revealed that the treatment led to a marked increase in
      the number of CD11b(+) TIDCs that killed the tumor cells via a TRAIL-dependent
      mechanism. Furthermore, acquisition of TRAIL expression by the CD11b(+) TIDCs was
      induced by BCG and dependent on signaling through TLR2, TLR4, and TLR9. In vivo
      transfer of Tregs abrogated the ability of BCG to induce CD11b(+) TIDCs to
      express TRAIL and thereby nullified the efficacy of the CTX-BCG treatment. Our
      data have therefore delineated what we believe to be a novel mechanism by which
      Tregs inhibit the antitumor immune response.

PMID- 18830417
TI  - Deletion of GSK-3beta in mice leads to hypertrophic cardiomyopathy secondary to
      cardiomyoblast hyperproliferation.
AB  - Based on extensive preclinical data, glycogen synthase kinase-3 (GSK-3) has been
      proposed to be a viable drug target for a wide variety of disease states, ranging
      from diabetes to bipolar disorder. Since these new drugs, which will be more
      powerful GSK-3 inhibitors than lithium, may potentially be given to women of
      childbearing potential, and since it has controversially been suggested that
      lithium therapy might be linked to congenital cardiac defects, we asked whether
      GSK-3 family members are required for normal heart development in mice. We report
      that terminal cardiomyocyte differentiation was substantially blunted in Gsk3b(-/
      ) embryoid bodies. While GSK-3alpha-deficient mice were born without a cardiac
      phenotype, no live-born Gsk3b(-/-) pups were recovered. The Gsk3b(-/-) embryos
      had a double outlet RV, ventricular septal defects, and hypertrophic myopathy,
      with near obliteration of the ventricular cavities. The hypertrophic myopathy was
      caused by cardiomyocyte hyperproliferation without hypertrophy and was associated
      with increased expression and nuclear localization of three regulators of
      proliferation - GATA4, cyclin D1, and c-Myc. These studies, which we believe are
      the first in mammals to examine the role of GSK-3alpha and GSK-3beta in the heart
      using loss-of-function approaches, implicate GSK-3beta as a central regulator of
      embryonic cardiomyocyte proliferation and differentiation, as well as of outflow
      tract development. Although controversy over the teratogenic effects of lithium
      remains, our studies suggest that caution should be exercised in the use of
      newer, more potent drugs targeting GSK-3 in women of childbearing age.

PMID- 18830421
TI  - Dissection of 6.5 dpc mouse embryos.
AB  - Analysis of gene expression patterns during early stages of mammalian embryonic
      development can provide important clues about gene function, cell-cell
      interaction and signaling mechanisms that guide embryonic patterning. However,
      dissection of the mouse embryo from the decidua shortly after implantation can be
      a challenging procedure, and detailed step-by-step documentation of this process
      is lacking. Here we demonstrate how post-implantation (6.5 dpc) embryos are
      isolated by first dissecting the uterus of a pregnant mouse (detection of the
      vaginal plug was designated day 0.5 poist coitum) and subsequently dissecting the
      embryo from maternal decidua. The dissection of Reichert's membrane is described
      as well as the removal of the ectoplacental cone.

PMID- 18830418
TI  - Molecular processes that handle -- and mishandle -- dietary lipids.
AB  - Overconsumption of lipid-rich diets, in conjunction with physical inactivity,
      disables and kills staggering numbers of people worldwide. Recent advances in our
      molecular understanding of cholesterol and triglyceride transport from the small
      intestine to the rest of the body provide a detailed picture of the fed/fasted
      and active/sedentary states. Key surprises include the unexpected nature of many
      pivotal molecular mediators, as well as their dysregulation - but possible
      reversibility - in obesity, diabetes, inactivity, and related conditions. These
      mechanistic insights provide new opportunities to correct dyslipoproteinemia,
      accelerated atherosclerosis, insulin resistance, and other deadly sequelae of
      overnutrition and underexertion.

PMID- 18830420
TI  - A possible mechanism underlying the effectiveness of acupuncture in the treatment
      of drug addiction.
AB  - Clinical trials are currently underway to determine the effectiveness of
      acupuncture in the treatment of drug addiction. While there are still many
      unanswered questions about the basic mechanisms of acupuncture, some evidence
      exists to suggest that acupuncture can play an important role in reducing
      reinforcing effects of abused drugs. The purpose of this article is to critically
      review these data. The neurochemical and behavioral evidence showed that
      acupuncture's role in suppressing the reinforcing effects of abused drugs takes
      place by modulating mesolimbic dopamine neurons. Also, several brain
      neurotransmitter systems such as serotonin, opioid and amino acids including GABA
      have been implicated in the modulation of dopamine release by acupuncture. These
      results provided clear evidence for the biological effects of acupuncture that
      ultimately may help us to understand how acupuncture can be used to treat abused
      drugs. Additional research using animal models is of primary importance to
      understanding the basic mechanism underlying acupuncture's effectiveness in the
      treatment of drug addiction.

PMID- 18830422
TI  - Transplantation of whole kidney marrow in adult zebrafish.

PMID- 18830423
TI  - Mouse dorsal forebrain explant isolation.

PMID- 18830424
TI  - Denaturing gradient gel electrophoresis (DGGE).

PMID- 18830425
TI  - Wolbachia bacterial infection in Drosophila.

PMID- 18830426
TI  - Culture of mouse neural stem cell precursors.
AB  - Primary neural stem cell cultures are useful for studying the mechanisms
      underlying central nervous system development. Stem cell research will increase
      our understanding of the nervous system and may allow us to develop treatments
      for currently incurable brain diseases and injuries. In addition, stem cells
      should be used for stem cell research aimed at the detailed study of mechanisms
      of neural differentiation and transdifferentiation and the genetic and
      environmental signals that direct the specialization of the cells into particular
      cell types. This video demonstrates a technique used to disaggregate cells from
      the embryonic day 12.5 mouse dorsal forebrain. The dissection procedure includes
      harvesting E12.5 mouse embryos from the uterus, removing the "skin" with fine
      dissecting forceps and finally isolating pieces of cerebral cortex. Following the
      dissection, the tissue is digested and mechanically dissociated. The resuspended
      dissociated cells are then cultured in "stem cell" media that favors growth of
      neural stem cells.

PMID- 18830427
TI  - Studying aggression in Drosophila (fruit flies).
AB  - Aggression is an innate behavior that evolved in the framework of defending or
      obtaining resources. This complex social behavior is influenced by genetic,
      hormonal and environmental factors. In many organisms, aggression is critical to
      survival but controlling and suppressing aggression in distinct contexts also has
      become increasingly important. In recent years, invertebrates have become
      increasingly useful as model systems for investigating the genetic and systems
      biological basis of complex social behavior. This is in part due to the diverse
      repertoire of behaviors exhibited by these organisms. In the accompanying video,
      we outline a method for analyzing aggression in Drosophila whose design
      encompasses important eco-ethological constraints. Details include steps for:
      making a fighting chamber; isolating and painting flies; adding flies to the
      fight chamber; and video taping fights. This approach is currently being used to
      identify candidate genes important in aggression and in elaborating the neuronal
      circuitry that underlies the output of aggression and other social behaviors.

PMID- 18830428
TI  - Tracheotomy: a method for transplantation of stem cells to the lung.
AB  - Lung disease is a leading cause of death and likely to become an epidemic given
      increases in pollution and smoking worldwide. Advances in stem cell therapy may
      alleviate many of the symptoms associated with lung disease and induce alveolar
      repair in adults. Concurrent with the ongoing search for stem cells applicable
      for human treatment, precise delivery and homing (to the site of disease) must be
      reassured for successful therapy. Here, I report that stem cells can safely be
      instilled via the trachea opening a non-stop route to the lung. This method
      involves a skin incision, caudal insertion of a cannula into and along the
      tracheal lumen, and injection of a stem cell vehicle mixture into airways of the
      lung. A broad range of media solutions and stabilizers can be instilled via
      tracheotomy, resulting in the ability to deliver a wider range of cell types.
      With alveolar epithelium confining these cells to the lumen, lung expansion and
      negative pressure during inhalation may also assist in stem cell integration.
      Tracheal delivery of stem cells, with a quick uptake and the ability to handle a
      large range of treatments, could accelerate the development of cell-based
      therapies, opening new avenues for treatment of lung disease.

PMID- 18830429
TI  - Testing visual sensitivity to the speed and direction of motion in lizards.
AB  - Testing visual sensitivity in any species provides basic information regarding
      behaviour, evolution, and ecology. However, testing specific features of the
      visual system provide more empirical evidence for functional applications.
      Investigation into the sensory system provides information about the sensory
      capacity, learning and memory ability, and establishes known baseline behaviour
      in which to gauge deviations (Burghardt, 1977). However, unlike mammalian or
      avian systems, testing for learning and memory in a reptile species is difficult.
      Furthermore, using an operant paradigm as a psychophysical measure of sensory
      ability is likewise as difficult. Historically, reptilian species have responded
      poorly to conditioning trials because of issues related to motivation,
      physiology, metabolism, and basic biological characteristics. Here, I demonstrate
      an operant paradigm used a novel model lizard species, the Jacky dragon
      (Amphibolurus muricatus) and describe how to test peripheral sensitivity to
      salient speed and motion characteristics. This method uses an innovative approach
      to assessing learning and sensory capacity in lizards. I employ the use of random
      dot kinematograms (RDKs) to measure sensitivity to speed, and manipulate the
      level of signal strength by changing the proportion of dots moving in a coherent
      direction. RDKs do not represent a biologically meaningful stimulus, engages the
      visual system, and is a classic psychophysical tool used to measure sensitivity
      in humans and other animals. Here, RDKs are displayed to lizards using three
      video playback systems. Lizards are to select the direction (left or right) in
      which they perceive dots to be moving. Selection of the appropriate direction is
      reinforced by biologically important prey stimuli, simulated by computer-animated
      invertebrates.

PMID- 18830430
TI  - Mouse adrenal chromaffin cell isolation.
AB  - Adrenal medullary chromaffin cell culture systems are extremely useful for the
      study of excitation-secretion coupling in an in vitro setting. This protocol
      illustrates the method used to dissect the adrenals and then isolate the
      medullary region by stripping away the adrenal cortex. The digestion of the
      medulla into single chromaffin cells is then demonstrated.

PMID- 18830431
TI  - Derivation of hematopoietic stem cells from murine embryonic stem cells.
AB  - A stem cell is defined as a cell with the capacity to both self-renew and
      generate multiple differentiated progeny. Embryonic stem cells (ESC) are derived
      from the blastocyst of the early embryo and are pluripotent in differentiative
      ability. Their vast differentiative potential has made them the focus of much
      research centered on deducing how to coax them to generate clinically useful cell
      types. The successful derivation of hematopoietic stem cells (HSC) from mouse ESC
      has recently been accomplished and can be visualized in this video protocol. HSC,
      arguably the most clinically exploited cell population, are used to treat a
      myriad of hematopoietic malignancies and disorders. However, many patients that
      might benefit from HSC therapy lack access to suitable donors. ESC could provide
      an alternative source of HSC for these patients. The following protocol
      establishes a baseline from which ESC-HSC can be studied and inform efforts to
      isolate HSC from human ESC. In this protocol, ESC are differentiated as embryoid
      bodies (EBs) for 6 days in commercially available serum pre-screened for optimal
      hematopoietic differentiation. EBs are then dissociated and infected with
      retroviral HoxB4. Infected EB-derived cells are plated on OP9 stroma, a bone
      marrow stromal cell line derived from the calvaria of M-CSF-/- mice, and co
      cultured in the presence of hematopoiesis promoting cytokines for ten days.
      During this co-culture, the infected cells expand greatly, resulting in the
      generation a heterogeneous pool of 100 s of millions of cells. These cells can
      then be used to rescue and reconstitute lethally irradiated mice.

PMID- 18830432
TI  - Dissection of imaginal discs from 3rd instar Drosophila larvae.

PMID- 18830433
TI  - Growth factor-coated bead placement on dorsal forebrain explants.

PMID- 18830434
TI  - Isolation and transplantation of hematopoietic stem cells (HSCs).

PMID- 18830436
TI  - Subchronic treatment with antiepileptic drugs modifies pentylenetetrazol-induced
      seizures in mice: Its correlation with benzodiazepine receptor binding.
AB  - Experiments using male CD1 mice were carried out to investigate the effects of
      subchronic (daily administration for 8 days) pretreatments with drugs enhancing
      GABAergic transmission (diazepam, 10 mg/kg, ip; gabapentin, 100 mg/kg, po; or
      vigabatrin, 500 mg/kg, po) on pentylenetetrazol (PTZ)-induced seizures, 24 h
      after the last injection. Subchronic administration of diazepam reduced latencies
      to clonus, tonic extension and death induced by PTZ. Subchronic vigabatrin
      produced enhanced latency to the first clonus but faster occurrence of tonic
      extension and death induced by PTZ. Subchronic gabapentin did not modify PTZ
      induced seizures. Autoradiography experiments revealed reduced benzodiazepine
      receptor binding in several brain areas after subchronic treatment with diazepam
      or gabapentin, whereas subchronic vigabatrin did not induce significant receptor
      changes. The present results indicate differential effects induced by the
      subchronic administration of diazepam, vigabatrin, and gabapentin on the
      susceptibility to PTZ-induced seizures, benzodiazepine receptor binding, or both.

PMID- 18830435
TI  - Levetiracetam in the treatment of epilepsy.
AB  - Epilepsy is a common chronic disorder that requires long-term antiepileptic drug
      therapy. Approximately one half of patients fail the initial antiepileptic drug
      and about 35% are refractory to medical therapy, highlighting the continued need
      for more effective and better tolerated drugs. Levetiracetam is an antiepileptic
      drug marketed since 2000. Its novel mechanism of action is modulation of synaptic
      neurotransmitter release through binding to the synaptic vesicle protein SV2A in
      the brain. Its pharmacokinetic advantages include rapid and almost complete
      absorption, minimal insignificant binding to plasma protein, absence of enzyme
      induction, absence of interactions with other drugs, and partial metabolism
      outside the liver. The availability of an intravenous preparation is yet another
      advantage. It has been demonstrated effective as adjunctive therapy for
      refractory partial-onset seizures, primary generalized tonic-clonic seizures, and
      myoclonic seizures of juvenile myoclonic epilepsy. In addition, it was found
      equivalent to controlled release carbamazepine as first-line therapy for partial
      onset seizures, both in efficacy and tolerability. Its main adverse effects in
      randomized adjunctive trials in adults have been somnolence, asthenia, infection,
      and dizziness. In children, the behavioral adverse effects of hostility and
      nervousness were also noted. Levetiracetam is an important addition to the
      treatment of epilepsy.

PMID- 18830437
TI  - Did depressive symptoms affect recognition of emotional prosody in Parkinson's
      disease?
AB  - OBJECTIVE: Evaluate the influence of depressive symptoms on the recognition of
      emotional prosody in Parkinson's disease (PD) patients, and identify types of
      emotion on spoken sentences. METHODS: Thirty-five PD patients and 65 normal
      participants were studied. Dementia was checked with the Mini Mental State
      Examination, Clinical Dementia Rating scale, and DSM IV. Recognition of emotional
      prosody was tested by asking subjects to listen to 12 recorded statements with
      neutral affective content that were read with a strong affective expression.
      Subjects had to recognize the correct emotion by one of four descriptors (angry,
      sad, cheerful, and neutral). The Beck Depression Inventory (BDI) was employed to
      rate depressive symptoms with the cutoff 14. RESULTS: Total ratings of emotions
      correctly recognized by participants below and above the BDI cutoff were similar
      among PD patients and normal individuals. PD patients who correctly identified
      neutral and anger inflections presented higher rates of depressive symptoms (p =
      0.011 and 0.044, respectively). No significant differences were observed in the
      normal group. CONCLUSIONS: Depression may modify some modalities of emotional
      prosody perception in PD, by increasing the perception of non-pleasant emotions
      or lack of affection, such as anger or indifference.

PMID- 18830438
TI  - Narcolepsy: current treatment options and future approaches.
AB  - The management of narcolepsy is presently at a turning point. Three main avenues
      are considered in this review: 1) Two tendencies characterize the conventional
      treatment of narcolepsy. Modafinil has replaced methylphenidate and amphetamine
      as the first-line treatment of excessive daytime sleepiness (EDS) and sleep
      attacks, based on randomized, double blind, placebo-controlled clinical trials of
      modafinil, but on no direct comparison of modafinil versus traditional
      stimulants. For cataplexy, sleep paralysis, and hypnagogic hallucinations, new
      antidepressants tend to replace tricyclic antidepressants and selective serotonin
      reuptake inhibitors (SSRIs) in spite of a lack of randomized, double blind,
      placebo-controlled clinical trials of these compounds; 2) The conventional
      treatment of narcolepsy is now challenged by sodium oxybate, the sodium salt of
      gammahydroxybutyrate, based on a series of randomized, double-blind, placebo
      controlled clinical trials and a long-term open label study. This treatment has a
      fairly good efficacy and is active on all symptoms of narcolepsy. Careful
      titration up to an adequate level is essential both to obtain positive results
      and avoid adverse effects; 3) A series of new treatments are currently being
      tested, either in animal models or in humans, They include novel stimulant and
      anticataplectic drugs, endocrine therapy, and, more attractively, totally new
      approaches based on the present state of knowledge of the pathophysiology of
      narcolepsy with cataplexy, hypocretine-based therapies, and immunotherapy.

PMID- 18830439
TI  - Once-daily treatment of ADHD with guanfacine: patient implications.
AB  - The standard of care for treating ADHD is to use a psychostimulant as the first
      line agent. Recent medical literature reports that approximately 70%-90% of
      patients with ADHD received some benefit from a stimulant medication. Even though
      psychostimulants have a high rate of efficacy, an estimated 30%-50% of children
      and adults may discontinue psychostimulants secondary to adverse effects or
      inadequate response. Guanfacine has been used for a number of years as an off
      label alternative to psychostimulants. This article reviews the current
      literature on the effectiveness of guanfacine in treating ADHD. It also
      introduces the preliminary data for guanfacine extended release and its
      effectiveness in decreasing the symptoms of ADHD.

PMID- 18830440
TI  - Heme oxygenase-1 induction in the brain during lipopolysaccharide-induced acute
      inflammation.
AB  - Delirium occurs in 23% of sepsis patients, in which pro-inflammatory cytokines
      and nitric oxide are suggested to be involved. However, in animal experiments,
      even a subseptic dose of lipopolysaccharide (LPS) injection induces both pro
      inflammatory cytokines and inducible nitric oxide synthase in the brain,
      suggesting that the brain oxidative reaction can be induced in the subseptic
      condition. Then, we evaluated the changes of heme oxygenase-1 (HO-1), a sensitive
      oxidative marker, as well as interleukin (IL)-1beta, IL-6, and inductible nitric
      oxide synthase (iNOS) mRNA in the hypothalamus and hippocampus of rats using real
      time PCR after peripheral injection of LPS (2.0 mg/kg). As a result, these four
      kinds of mRNAs were induced significantly in both areas after LPS injection.
      These results suggest that peripheral inflammation induces an oxidative reaction
      in the brain, even if the inflammation is not lethal. It is also considered that
      several pathways are involved in brain HO-1 induction.

PMID- 18830441
TI  - Cost-effectiveness of drug therapies for Alzheimer's disease: A brief review.
AB  - Alzheimer's disease (AD) is an important and rapidly expanding public health
      problem. Its large economic burden is a result of its disabling nature,
      chronicity, and high prevalence in older segments of the population. Current
      treatments of AD have been criticized for providing insufficient benefit to
      justify their costs, but variability in assessing both costs and benefits make
      evaluation of the existing data problematic. Inclusion of the value of caregiver
      time is a major driver of the determination of cost-effectiveness. Population
      based studies and those based on application of economic models to other study
      outcomes tend to identify greater cost-effectiveness than prospectively collected
      data. Differences in healthcare economics across countries also limit
      generalization of specific study findings. The current state of evidence suggests
      that treatment decisions in AD should be based on assessment of benefit in
      individual patients rather than broader societal economic factors.

PMID- 18830442
TI  - Amisulpride plus valproate vs haloperidol plus valproate in the treatment of
      acute mania of bipolar I patients: a multicenter, open-label, randomized,
      comparative trial.
AB  - The primary objective of this study was to compare the effectiveness of
      combination treatment of valproate and amisulpride with that of valproate and
      haloperidol in bipolar I disorder. Adult inpatients with a current manic episode
      fulfilling DSM-IV-TR diagnostic criteria for bipolar type I disorder were
      included. Patients were randomized to amisulpride (400-800 mg/day) or haloperidol
      (5-15 mg/day) for 3 months and all received valproate. The primary effectiveness
      criterion was the percentage of responders (defined by a decrease of >/=50% of
      the Y-MRS) in patients completing the study. Safety was evaluated by adverse
      event reporting, determination of extrapyramidal function and clinical
      examination. Sixty-two patients were randomized to receive valproate-amisulpride,
      and 61 to receive valproate-haloperidol. At study end, responder rates were 72.6%
      in the amisulpride group and 65.5% in the haloperidol group. Remission rates were
      83.9% and 89.7%, respectively. At study end, neither response rates nor remission
      rates differed significantly between groups. Treatment-emergent adverse events
      occurred significantly (p = 0.009) more frequently in the haloperidol group
      (86.4%) than in the amisulpride group (66.1%). In conclusion, the valproate
      amisulpride combination was as effective as the valproate - haloperidol
      combination in bipolar I patients, with a better safety profile.

PMID- 18830443
TI  - Estrogenic activities of Fatty acids and a sterol isolated from royal jelly.
AB  - We have previously reported that royal jelly (RJ) from honeybees (Apis mellifera)
      has weak estrogenic activity mediated by interaction with estrogen receptors that
      leads to changes in gene expression and cell proliferation. In this study, we
      isolated four compounds from RJ that exhibit estrogenic activity as evaluated by
      a ligand-binding assay for the estrogen receptor (ER) beta. These compounds were
      identified as 10-hydroxy-trans-2-decenoic acid, 10-hydroxydecanoic acid, trans-2
      decenoic acid and 24-methylenecholesterol. All these compounds inhibited binding
      of 17beta-estradiol to ERbeta, although more weakly than diethylstilbestrol or
      phytoestrogens. However, these compounds had little or no effect on the binding
      of 17beta-estradiol to ERalpha. Expression assays suggested that these compounds
      activated ER, as evidenced by enhanced transcription of a reporter gene
      containing an estrogen-responsive element. Treatment of MCF-7 cells with these
      compounds enhanced their proliferation, but concomitant treatment with tamoxifen
      blocked this effect. Exposure of immature rats to these compounds by subcutaneous
      injection induced mild hypertrophy of the luminal epithelium of the uterus, but
      was not associated with an increase in uterine weight. These findings provide
      evidence that these compounds contribute to the estrogenic effect of RJ.

PMID- 18830444
TI  - Dominican Children with HIV not Receiving Antiretrovirals: Massage Therapy
      Influences their Behavior and Development.
AB  - Forty-eight children (M age = 4.8 years) infected with HIV/AIDS and living in the
      Dominican Republic were randomly assigned to a massage therapy or a play session
      control group. The children in the massage therapy group received two weekly 20
      min massages for 12 weeks; the children in the control group participated in a
      play session (coloring, playing with blocks) for the same duration and length as
      the massage therapy group. Overall, the children in the massage therapy group
      improved in self-help abilities and communication, suggesting that massage
      therapy may enhance daily functioning for children with HIV/AIDS. Moreover, the
      HIV infected children who were six or older also showed a decrease in
      internalizing behaviors; specifically depressive/anxious behaviors and negative
      thoughts were reduced. Additionally, baseline assessments revealed IQ equivalence
      below normal functioning for 70% of the HIV infected children and very high
      incidences of mood problems (depression, withdrawn) for 40% of the children and
      anxiety problems for 20% of the children, suggesting the need for better
      monitoring and alternative interventions in countries with limited resources to
      improve cognition and the mental health status of children infected with
      HIV/AIDS.

PMID- 18830445
TI  - Red Cabbage (Brassica oleracea) Ameliorates Diabetic Nephropathy in Rats.
AB  - The protective action against oxidative stress of red cabbage (Brassica oleracea)
      extract was investigated. Diabetes was induced in male Wistar rats using
      streptozotocin (60 mg/kg body weight). Throughout the experimental period (60
      days), diabetic rats exhibited many symptoms including loss of body weight,
      hyperglycemia, polyuria, polydipsia, renal enlargement and renal dysfunction.
      Significant increase in malondialdehyde, a lipid peroxidation marker, was
      observed in diabetic kidney. This was accompanied by a significant increase in
      reduced glutathione and superoxide dismutase activity and a decrease in catalase
      activity and in the total antioxidant capacity of the kidneys. Daily oral
      ingestion (1 g/kg body weight) of B. oleracea extract for 60 days reversed the
      adverse effect of diabetes in rats. B. oleracea extract lowered blood glucose
      levels and restored renal function and body weight loss. In addition, B. oleracea
      extract attenuated the adverse effect of diabetes on malondialdehyde, glutathione
      and superoxide dismutase activity as well as catalase activity and total
      antioxidant capacity of diabetic kidneys. In conclusion, the antioxidant and
      antihyperglycemic properties of B. oleracea extract may offer a potential
      therapeutic source for the treatment of diabetes.

PMID- 18830446
TI  - Comparison of pharmacopuncture, aquapuncture and acepromazine for sedation of
      horses.
AB  - Pharmacopuncture, the injection of subclinical doses of drugs into acupoints
      reduces drug undesirable side effects, residues in animal consumption products
      and treatment costs in large animals. Acepromazine (Acp) produces several
      undesirable effects, such as hypotension. Previous studies with the injection of
      1/10 of Acp dose in dog acupoints showed its advantage for sedation, minimizing
      undesirable effects. Eight horses were randomly submitted to four different
      treatment protocols according to a Latin Square double-blind design: (i) 0.1 ml
      kg(-1) of saline subcutaneously injected at the cervical region, (ii) 0.1 mg kg(
      1) of Acp injected subcutaneously at the cervical region, (iii) 0.01 ml kg(-1) of
      saline injected into GV1 acupoint (aquapuncture) and (iv) 0.01 mg kg(-1) of Acp
      injected into GV1 acupoint (pharmacopuncture). Heart rate, respiratory rate, head
      height and degree of sedation were measured before and at 30, 60 and 90 min after
      treatments. Signs of sedation were observed in all treated groups at 30 min and
      only in 1/10Acp-GV1 at 60 min after the treatments. Only the group treated with
      0.1 mg kg(-1) of Acp s.c. had significantly lower values of head height at 30
      min. Respiratory rate tended to reduce in all groups but was significantly lower
      only in horses treated with 0.1 mg kg(-1) of Acp s.c. Heart rate remained
      unchanged in all groups. Acp-pharmacopuncture on GV1 in horses produced a mild
      sedation when compared with the conventional dose of Acp. More investigations are
      necessary to determine the optimal dosage of Acp-pharmacopuncture for sedation in
      horses.

PMID- 18830447
TI  - eCAM: Early Harvest.

PMID- 18830448
TI  - Chondroprotective Potential of Fruit Extracts of Phyllanthus emblica in
      Osteoarthritis.
AB  - There is a need for effective nutraceuticals for osteoarthritis care. The fruit
      of Phyllanthus emblica is used as a powerful rejuvenator in Ayurvedic medicine.
      This study measured the chondroprotective potential of P. emblica ('Amalaki')
      fruits in vitro. We used aqueous extracts of unprocessed P. emblica fruit powder
      (powder A), and the powder obtained after hot water extraction and drying of
      powder A (powder B). Chondroprotection was measured in three different assay
      systems. First, we tested the effects of both fruit powders on the activities of
      the enzymes hyaluronidase and collagenase type 2. Second, an in vitro model of
      cartilage degradation was set-up with explant cultures of articular knee
      cartilage from osteoarthritis patients. Cartilage damage was assayed by measuring
      glycosaminoglycan release from explants treated with/without P. emblica fruit
      powders. Aqueous extracts of both fruit powders significantly inhibited the
      activities of hyaluronidase and collagenase type 2 in vitro. Third, in the
      explant model of cartilage matrix damage, extracts of glucosamine sulphate and
      powder B (0.05 mg/ml) exhibited statistically significant, long-term
      chondroprotective activity in cartilage explants from 50% of the patients tested.
      This result is important since glucosamine sulphate is the leading nutraceutical
      for osteoarthritis. Powder A induced a statistically significant, short-term
      chondroprotective activity in cartilage explants from all of the patients tested.
      This is the first study to identify and quantitate new chondroprotective
      activities of P. emblica fruits. These data provide pilot pre-clinical evidence
      for the use of P. emblica fruits as a chondroprotective agent in osteoarthritis
      therapy.

PMID- 18830449
TI  - Chemical composition and botanical origin of red propolis, a new type of
      brazilian propolis.
AB  - Red propolis is a new type of Brazilian propolis. This material, as well as the
      secretions of 20 plant species that are often mentioned as its probable botanical
      source, have been investigated by RP-HPTLC. Phytochemical evidence based on UV
      VIS spectra, RP-HPLC and GC-MS, showed Dalbergia ecastophyllum (L.) Taub. to be
      the main source of red propolis in Alagoas state. The propolis and plant resin
      showed high relative percentages of the isoflavonoids 3-Hydroxy-8,9
      dimethoxypterocarpan and medicarpin. To our knowledge this is the first report of
      the secretion of a leguminous species being the source of propolis.

PMID- 18830450
TI  - Can Vitex Agnus Castus be Used for the Treatment of Mastalgia? What is the
      Current Evidence?
AB  - There have been many treatments suggested for the management of mastalgia; one of
      these is the fruit extract of Vitex Agnus castus L. commonly known as Agnus
      castus, an extract of a deciduous shrub native to Mediterranean Europe and
      Central Asia. It is postulated that A. castus suppresses the stress-induced
      latent hyperprolactinemia which is a release of supra-physiological levels of
      prolactin in some patients in response to stressful stimuli. It is postulated
      that A. castus could be effective in the treatment of cyclical mastalgia by
      inhibiting the release of excess prolactin by blocking Dopamine-2 receptor type
      on pituitary. The adverse events following A. castus treatment are mild and
      reversible. The aim of this review is assess the efficacy of A. castus in the
      treatment of mastalgia. Data from randomized and non-randomized studies regarding
      the efficacy and safety of A. castus is reviewed in a systematic fashion. It is
      concluded that A. castus can be considered as an efficient alternative
      phytotherapeutic agent in the treatment of mastalgia.

PMID- 18830451
TI  - A randomized pilot study of atractylenolide I on gastric cancer cachexia
      patients.
AB  - We determined the therapeutic efficacy of atractylenolide I (ATR), extracted from
      largehead atractylodes rhizome, in managing gastric cancer cachexia (GCC), and
      interpreted its probable pharmacological mechanism via investigating tumor
      necrosis factor alpha (TNF-alpha), interleukin-1 (IL-1), interleukin-6 (IL-6) and
      proteolysis-inducing factor (PIF). This was a randomized but not-blinded pilot.
      The study group (n = 11) received 1.32 g per day of atractylenolide I (ATR) and
      the control group (n = 11) received 3.6 g per day of fish-oil-enriched
      nutritional supplementation (FOE) for 7 weeks. Conservative therapy was similar
      in both groups. Clinical [appetite, body weight, mid-arm muscle circumference
      (MAMC), Karnofsky performance status (KPS) status], biomarker (TNF-alpha, IL-1,
      IL-6 and PIF) were evaluated in the basal state, at the third and seventh weeks.
      To analyze changes of cytokines, an immumohistochemistry technique was adopted.
      Base line characteristics were similar in both groups. Effects on MAMC and body
      weight increase, TNF-alpha increase and IL-1 decreases of serum level were
      significant in both groups (P < 0.05). ATR was significantly more effective than
      FOE in improving appetite and KPS status, and decreasing PIF positive rate (P <
      0.05). Slight nausea (3/11) and dry mouth (1/11) were shown in intervention
      groups but did not interrupt treatment. These preliminary findings suggest that
      ATR might be beneficial in alleviating symptoms, in modulating cytokine and in
      inhibiting PIF proteolysis of gastric cancer cachexia. Further research using a
      randomized controlled design is necessary to confirm these pilot study findings.

PMID- 18830452
TI  - Entropy-based model for interpreting life systems in traditional chinese
      medicine.
AB  - Traditional Chinese medicine (TCM) treats qi as the core of the human life
      systems. Starting with a hypothetical correlation between TCM qi and the entropy
      theory, we address in this article a holistic model for evaluating and unveiling
      the rule of TCM life systems. Several new concepts such as acquired life entropy
      (ALE), acquired life entropy flow (ALEF) and acquired life entropy production
      (ALEP) are propounded to interpret TCM life systems. Using the entropy theory,
      mathematical models are established for ALE, ALEF and ALEP, which reflect the
      evolution of life systems. Some criteria are given on physiological activities
      and pathological changes of the body in different stages of life. Moreover, a
      real data-based simulation shows life entropies of the human body with different
      ages, Cold and Hot constitutions and in different seasons in North China are
      coincided with the manifestations of qi as well as the life evolution in TCM
      descriptions. Especially, based on the comparative and quantitative analysis, the
      entropy-based model can nicely describe the evolution of life entropies in Cold
      and Hot individuals thereby fitting the Yin-Yang theory in TCM. Thus, this work
      establishes a novel approach to interpret the fundamental principles in TCM, and
      provides an alternative understanding for the complex life systems.

PMID- 18830453
TI  - An Evaluation of the Additive Effect of Natural Herbal Medicine on SARS or SARS
      like Infectious Diseases in 2003: A Randomized, Double-blind, and Controlled
      Pilot Study.
AB  - Natural herbal medicine (NHM) has been used to control infectious diseases for
      thousands of years. In view of the possible beneficial effect of NHM on SARS, we
      conducted this study to examine whether NHM is of any benefit as a supplementary
      treatment of SARS or SARS-like infectious disease. This was a randomized, double
      blind, placebo-controlled trial. Twenty-eight patients fulfilled the WHO
      inclusion criteria and our exclusion criteria. All enrolled patients received
      routine western-medicine treatment. Patients were randomly allocated to one of
      the three supplementary treatment groups: NHM A (Group A, n = 9) NHM B (Group B,
      n = 9) or placebo (Group C, n = 10). Chest X-ray was done every 1 or 2 days for
      every patient. Reading radiologists use a standard 0-3 scoring system (0: no
      infiltration; 1: focal haziness or even small patchy lesion; 2: ground glass
      picture; 3: lobar consolidation) according to the severity of infiltration in
      each lung field (three lung fields in both right and left lungs). The main
      outcome measurements were the improving chest radiographic scores (IRS) and the
      duration (days) till improvement (DI). One patient from the placebo group passed
      away. Patients from NHM A took less days before showing improvement (6.7 +/- 1.8)
      compared with placebo group (11.2 +/- 4.9), which showed statistical significance
      (P = 0.04). The cases were too few to be conclusive, the initial observations
      seem to indicate NHM appears to be safe in non-criticallly ill patients and
      clinical trials are feasible in the setting of pandemic outbreaks.

PMID- 18830454
TI  - Brazilian propolis: correlation between chemical composition and antimicrobial
      activity.
AB  - The chemical composition of ethanol extracts from samples of Brazilian propolis
      (EEPs) determined by HPLC and their activity against Trypanosoma cruzi,
      Staphylococcus aureus, Streptococcus pneumoniae, Klebisiella pneumoniae, Candida
      albicans, Sporothrix schenckii and Paracoccidioides brasiliensis were determined.
      Based on the predominant botanical origin in the region of samples' collection,
      the 10 extracts were separated into three groups: A (B. dracunculifolia +
      Auraucaria spp), B (B. dracunculifolia) and C (Araucaria spp). Analysis by the
      multiple regression of all the extracts together showed a positive correlation,
      higher concentrations leading to higher biological effect, of S. aureus with p
      coumaric acid (PCUM) and 3-(4-hydroxy-3-(oxo-butenyl)-phenylacrylic acid (DHCA1)
      and of trypomastigotes of T. cruzi with 3,5-diprenyl-4-hydroxycinnamic acid
      derivative 4 (DHCA4) and 2,2-dimethyl-6-carboxyethenyl-2H-1-benzopyran (DCBEN).
      When the same approach was employed for each group, due to the small number of
      observations, the statistical test gave unreliable results. However, an overall
      analysis revealed for group A an association of S. aureus with caffeic acid (CAF)
      and dicaffeoylquinic acid 3 (CAFQ3), of S. pneumoniae with CAFQ3 and
      monocaffeoylquinic acid 2 (CAFQ2) and of T. cruzi also with CAFQ3. For group B, a
      higher activity against S. pneumoniae was associated DCBEN and for T. cruzi with
      CAF. For group C no association was observed between the anitmicrobial effect and
      any component of the extracts. The present study reinforces the relevance of PCUM
      and derivatives, especially prenylated ones and also of caffeolyquinic acids, on
      the biological activity of Brazilian propolis.

PMID- 18830455
TI  - Inhibitory Effects of Bangladeshi Medicinal Plant Extracts on Interactions
      between Transcription Factors and Target DNA Sequences.
AB  - Several transcription factors (TFs) play crucial roles in governing the
      expression of different genes involved in the immune response, embryo or cell
      lineage development, cell apoptosis, cell cycle progression, oncogenesis, repair
      and fibrosis processes and inflammation. As far as inflammation, TFs playing
      pivotal roles are nuclear factor kappa B (NF-kB), activator protein (AP-1),
      signal transducer and activator of transcription (STATs), cAMP response element
      binding protein (CREB) and GATA-1 factors. All these TFs regulate the expression
      of pro-inflammatory cytokines and are involved in the pathogenesis of a number of
      human disorders, particularly those with an inflammatory component. Since several
      medicinal plants can be employed to produce extracts exhibiting biological
      effects and because alteration of gene transcription represents a very
      interesting approach to control the expression of selected genes, this study
      sought to verify the ability of several extracts derived from Bangladeshi
      medicinal plants in interfering with molecular interactions between different TFs
      and specific DNA sequences. We first analyzed the antiproliferative activity of
      19 medicinal plants on different human cell lines, including erythroleukemia
      K562, B lymphoid Raji and T lymphoid Jurkat cell lines. Secondly, we employed the
      electrophoretic mobility shift assay as a suitable technique for a fast screening
      of plant extracts altering the binding between NF-kB, AP-1, GATA-1, STAT-3, CREB
      and the relative target DNA elements.

PMID- 18830456
TI  - Mechanism of reflex regulation of the gastroduodenal function by acupuncture.
AB  - Many clinical studies focus on the effects of acupuncture on digestive disorders.
      However, few studies describe the mechanism by which these effects are produced.
      We present some recent experimental work on the mechanism of acupuncture for
      reflex regulation of gastroduodenal function in anesthetized rats. In
      anesthetized rats, it has been proven that acupuncture to the abdomen excites
      sympathetic nerves via spinal reflexes causing inhibition of motilities while
      acupuncture of limbs excites vagus nerves via supraspinal reflexes causing an
      increase in the motilities. It has also been shown that in order to inhibit
      gastric motilities, acupuncture stimulation of the abdomen must be strong enough
      to excite group VI fibers of the afferent intercostal nerves. To increase gastric
      motilities, acupuncture stimulation to hind limbs must be strong enough to excite
      the high-threshold group III fibers of tibial nerves. It has also been shown that
      the neural mechanism of duodenal motility stimulation by acupuncture involves the
      same body regions and intensity of stimulation as that of gastric motilities.
      Theories regarding the underlying mechanism have proposed somato-autonomic
      reflexes and responses via endogenous opioids, etc., but without definitive
      conclusions.

PMID- 18830457
TI  - Second World Ayurveda Congress (Theme: Ayurveda for the Future)-Inaugural
      Address: Part II.

PMID- 18830458
TI  - Herbex-kid Inhibits Immediate Hypersensitivity Reactions in Mice and Rats.
AB  - Herbex-kid (HK), a polyherbal formulation was evaluated in various experimental
      allergic models of Type I hypersensitivity reactions. Compound 48/80 (C 48/80)
      has been shown to induce rat mesentery mast cell degranulation and HK (1.07,
      10.75 and 107.5 mg ml(-1)) inhibited the mast cell degranulation in a dose
      dependent manner. HK (1.07, 10.75 and 107.5 mg kg(-1); p.o.) showed dose
      dependent protection against C 48/80 induced systemic anaphylaxis in male Balb/C
      mice. In active anaphylaxis model, male Wistar rats orally administered with
      10.75 and 107.5 mg kg(-1) of HK showed significant (P < 0.01) protection against
      mast cell degranulation, while in passive anaphylaxis model, only at 107.5 mg kg(
      1) showed significant (P < 0.01) reduction in mast cell degranulation. HK at all
      dose levels was able to significantly decrease the time spent in nasal rubbing in
      Wistar rats sensitized to ovalbumin, while only at 107.5 mg kg(-1) it showed
      significant (P < 0.01) reduction in number of sneezes. In C 48/80-induced skin
      itch model, all dose levels of HK significantly (P < 0.001) decreased the time
      spent in itching and the number of itches. HK did not produce any significant
      inhibition in histamine induced contraction in guinea pig ileum. From the above
      findings we conclude that the HK possesses antiallergic activity mediated by
      reducing of the release mediators from mast cells and also by 5-HT antagonism
      without the involvement of histamine (H1) receptors.

PMID- 18830459
TI  - Aromatherapy massage affects menopausal symptoms in korean climacteric women: a
      pilot-controlled clinical trial.
AB  - This study investigated the effects of aromatherapy massage on menopausal
      symptoms in Korean climacteric women. Kupperman's menopausal index was used to
      compare an experimental group of 25 climacteric women with a wait-listed control
      group of 27 climacteric women. Aromatherapy was applied topically to subjects in
      the experimental group in the form of massage on the abdomen, back and arms using
      lavender, rose geranium, rose and jasmine in almond and primrose oils once a week
      for 8 weeks (eight times in total). The experimental group reported a
      significantly lower total menopausal index than wait-listed controls (P < 0.05).
      There were also significant intergroup differences in subcategories such as
      vasomotor, melancholia, arthralgia and myalgia (all P < 0.05). These findings
      suggest that aromatherapy massage may be an effective treatment of menopausal
      symptoms such as hot flushes, depression and pain in climacteric women. However,
      it could not be verified whether the positive effects were from the aromatherapy,
      the massage or both. Further rigorous studies should be done with more objective
      measures.

PMID- 18830460
TI  - Computational and experimental tools in solving some mechanistic problems in the
      chemistry of Fischer carbene complexes.
AB  - Well-established bonding situations of organometallic complexes and extensive
      applications in synthesis have been achieved during the past 25 years. In
      contrast, very little attention has been devoted to the intimate understanding of
      their reaction mechanisms. In this feature article, we show how the combined use
      of experimental and computational tools can be used to explore some reaction
      mechanisms of Fischer-type carbene complexes. The results obtained clearly
      demonstrate the usefulness of these combined tools to unravel the intimacies of
      different thermal and photochemical transformations, not only to explain already
      known processes but to predict new reactivity involving these fascinating
      complexes.

PMID- 18830461
TI  - Kagome network compounds and their novel magnetic properties.
AB  - Compounds possessing the Kagome network are truly interesting because of their
      unusual low-energy properties. They exhibit magnetic frustration because of the
      triangular lattice inherent to the hexagonal bronze structure they possess, as
      indeed demonstrated by some of the Fe(3+) jarosites, but this is not the general
      case. Kagome compounds formed by transition metal ions with varying spins exhibit
      novel magnetic properties, some even showing evidence for magnetic order and
      absence of frustration. We describe the structure and magnetic properties of this
      interesting class of materials and attempt to provide an explanation for the
      variety of properties on the basis of theoretical considerations.

PMID- 18830462
TI  - Enantioselective organocatalytic conjugate addition of alpha-aminoketone to
      nitroolefins.
AB  - The enantioselective organocatalytic conjugate addition of alpha-aminoketone to
      nitroolefins is reported.

PMID- 18830463
TI  - Temperature-triggered gate opening for gas adsorption in microporous manganese
      formate.
AB  - Microporous manganese formate shows temperature-triggered gate opening for
      nitrogen and argon adsorption, which is not due to a structural change of the
      framework but due to dynamic opening of the pore aperture and/or sufficient
      kinetic energy of the adsorbates to overcome a diffusion barrier above a critical
      temperature.

PMID- 18830464
TI  - Synergistic effects in gene delivery-a structure-activity approach to the
      optimisation of hybrid dendritic-lipidic transfection agents.
AB  - Novel gene delivery agents based on combining cholesterol units with spermine
      functionalised dendrons exhibit enhanced transfection ability-we report
      significant synergistic effects in mixed (hybrid) systems which combine aspects
      of both main classes of synthetic vectors, i.e., cationic polymers and lipids.

PMID- 18830465
TI  - Solution identification and solid state characterisation of a heterometallic
      polyoxometalate {Mo(11)V(7)}: [Mo(VI)(11)V(V)(5)V(IV)(2)O(52)(mu(9)-SO(3))](7-).
AB  - A polyoxomolybdenum/vanadium-sulfite {M(18)} cluster-based compound,
      [Mo(VI)(11)V(V)(5)V(IV)(2)O(52)(mu(9)-SO(3))](7-), is reported that exhibits a
      unique structural motif, arising from the incorporation of five V(V) and two
      V(IV) ions into a {M(18)} cluster framework templated by SO(3)(2-); this cluster
      compostion was first identified using cryospray mass spectrometry.

PMID- 18830466
TI  - Arsenic-containing hydrocarbons: natural compounds in oil from the fish capelin,
      Mallotus villosus.
AB  - Arsenic-containing hydrocarbons have been identified for the first time as
      natural components of fish oil.

PMID- 18830467
TI  - Total synthesis of the marine macrolide (+)-neopeltolide.
AB  - A concise total synthesis of the antiproliferative macrolide (+)-neopeltolide has
      been completed, utilising a Jacobsen hetero Diels-Alder reaction to install the
      trisubstituted tetrahydropyran ring.

PMID- 18830469
TI  - Soluble precursors of 2,3-naphthalocyanine and phthalocyanine for use in thin
      film transistors.
AB  - Soluble precursors of 2,3-naphthalocyanine (Nc) and phthalocyanine (Pc) were
      prepared and were converted into insoluble semiconducting thin films of Pc and Nc
      by heating after fabrication via spin-coating.

PMID- 18830468
TI  - A persistent P,N-heterocyclic carbene.
AB  - Conjugate acids of cyclic (amino)(phosphino)carbenes (P-NHCs) have been prepared,
      and several different processes have been observed during their deprotonation,
      which include the formation of a metastable P-NHC, an azomethine ylide, and a
      bicyclic phosphirane.

PMID- 18830470
TI  - Multinuclear alkylaluminium macrocyclic Schiff base complexes: influence of
      procatalyst structure on the ring opening polymerisation of epsilon-caprolactone.
AB  - Two remote dialkylaluminium centres supported by a macrocyclic Schiff base ligand
      exhibited beneficial cooperative effects, whilst aluminoxane-type bonding proved
      to be detrimental to activity for the ring opening polymerisation of epsilon
      caprolactone.

PMID- 18830471
TI  - Total syntheses of (+/-)-montanin A and (+/-)-teuscorolide.
AB  - The first total syntheses of (+/-)-montanin A and (+/-)-teuscorolide have been
      achieved from an advanced precursor previously developed via a Diels-Alder
      strategy; in the synthetic sequence, the synthesis of montanin A was first
      accomplished in 8 steps, from which teuscorolide was readily achieved in 2 steps
      by using a novel furan oxidative cyclization-retro-cyclization process as a key
      operation.

PMID- 18830472
TI  - Void and filled supramolecular nanoprisms-notable differences between seemingly
      identical construction principles.
AB  - Void and filled supramolecular nanoprisms (void: 4900 A(3)) were furnished in
      quantitative yield utilising the (terpyridine)-Zn(2+)-(phenanthroline) complex as
      a dynamic and heteroleptic building motif (HETTAP approach), but only if units
      serving as panels and pillars in the self-assembly were optimised with regard to
      their kinetic behaviour.

PMID- 18830473
TI  - Hexagonal crystalline inclusion complexes of 4-iodophenoxy trimesoate.
AB  - Bifurcated Ipi and IO[double bond, length as m-dash]C halogen bonding
      interactions assist in formation of unique iodo-arene trimers leading to
      nanoscale channels in inclusion complexes of trimesic acid iodophenolate.

PMID- 18830475
TI  - Effect of the nature of the metal on the breathing steps in MOFs with dynamic
      frameworks.
AB  - The thermal behaviour of the nanoporous iron(iii) terephthalate MIL-53 is in
      stark contrast to its chromium and aluminium analogues which show an expansion of
      the cell during dehydration; with iron, reversible dehydration occurs via
      evolution of the structure through a highly distorted metastable anhydrous phase
      to a more regular phase above 423 K in which pore volume remains approximately
      constant.

PMID- 18830474
TI  - One-pot synthesis and characterizations of bi-functional phosphor-magnetic
      @SiO(2) nanoparticles: controlled and structured association of Mo(6) cluster
      units and gamma-Fe(2)O(3) nanocrystals.
AB  - Nanostructured silica coated bifunctional nanoparticles based on [Mo(6)Br(14)](2
      ) units as phosphorescent dye and magnetic gamma-Fe(2)O(3) nanocrystals were
      synthesized and characterized.

PMID- 18830476
TI  - Chemical and optical control of peristaltic actuator based on self-oscillating
      porous gel.
AB  - We demonstrate the chemical and optical control of the self-sustaining
      peristaltic motion of a structural colored porous hydrogel.

PMID- 18830477
TI  - Microporous vanadyl-arsenate with the template incorporated exhibiting sorption
      and catalytic properties.
AB  - (C(5)H(14)N(2))[(VO)(3)(AsO(4))(HAsO(4))(2)(OH)].3H(2)O behaves as a microporous
      organically templated compound, with reversible adsorption and desorption of N(2)
      at 77 K, and as an extremely efficient catalyst that catalyzes selective
      sulfoxide formation from organic sulfides, under mild conditions.

PMID- 18830478
TI  - The origin of open circuit voltage of porphyrin-sensitised TiO(2) solar cells.
AB  - Electron lifetime and diffusion coefficient measurements in highly efficient
      porphyrin-sensitised TiO(2) solar cells showed reduced electron lifetime, and
      consequently, lower photo-induced electron density under illumination compared to
      commonly used ruthenium dye (N719)-sensitised solar cells, which is proposed to
      be the origin of the generally lower open circuit voltage.

PMID- 18830479
TI  - A reassessment of the association between azulene and [60]fullerene. Possible
      pitfalls in the determination of binding constants through fluorescence
      spectroscopy.
AB  - We show here that the recently reported surprisingly large association constant
      (K = 7.6 x 10(4) M(-1)) between azulene and [60]fullerene is due to experimental
      artifacts, pointing out potential errors in the characterization of association
      equilibria by fluorescence spectroscopy, and suggesting the best experimental
      practices.

PMID- 18830480
TI  - A [(NHC)CuCl] complex as a latent Click catalyst.
AB  - A latent catalyst for the [3+2] cycloaddition reaction of azides and alkynes has
      been developed in accordance with the principles of Click chemistry.

PMID- 18830481
TI  - A general approach to triphenylenes and azatriphenylenes: total synthesis of
      dehydrotylophorine and tylophorine.
AB  - A convergent and flexible synthesis of substituted triphenylenes,
      azatriphenylenes, and the cytotoxic alkaloids dehydrotylophorine and tylophorine
      has been developed.

PMID- 18830482
TI  - Selected regiocontrolled transformations applied to the synthesis of (1S)-cis
      chrysanthemic acid from (1S)-3,4-epoxy-2,2,5,5-tetramethylcyclohexanol.
AB  - (1S)-cis-Chrysanthemic acid has been prepared in a few steps with complete
      control of the relative and absolute stereochemistry using regiocontrolled
      epoxide ring opening, diol mono-oxidation and cyclopropanation.

PMID- 18830483
TI  - One-pot synthesis of a shape-persistent endo-functionalised nano-sized adamantoid
      compound.
AB  - A simple approach by reversible imine condensation to shape-persistent endo
      functionalised nanocage compounds is presented.

PMID- 18830484
TI  - Highly sensitive and selective detection of Hg(2+) in aqueous solution with
      mercury-specific DNA and Sybr Green I.
AB  - Sybr Green I efficiently discriminates mercury-specific DNA and mercury-specific
      DNA/Hg(2+) complex, which provides a label-free, fast, fluorescence turn on assay
      for Hg(2+) detection with high sensitivity and selectivity.

PMID- 18830485
TI  - Ligand exchanged photoluminescent gold quantum dots functionalized with leading
      peptides for nuclear targeting and intracellular imaging.
AB  - Ligand exchanged gold quantum dots (GQDs) conjugated with cell-penetrating
      peptides are a new class of photoluminescent probes for nuclear targeting and
      intracellular imaging.

PMID- 18830486
TI  - Lysine and arginine residues do not increase the helicity of alanine-rich peptide
      helices.
AB  - The helix-disfavoring, versus alanine, propagation values of lysine (0.8) and
      arginine (1.0) residues placed centrally in an (Ala)(9) unit have been measured
      by (13)C NMR.

PMID- 18830487
TI  - Auto-hydroxylation of FIH-1: an Fe(ii), alpha-ketoglutarate-dependent human
      hypoxia sensor.
AB  - HIF-asparaginyl hydroxylase (FIH-1) normally couples O(2)-activation to
      hydroxylation of Asn(803) on the alpha-subunit of the hypoxia-inducible factor
      (HIFalpha), a key step in pO(2) sensing; in the absence of HIFalpha, O(2)
      activation becomes uncoupled, leading to self-hydroxylation at Trp(296) and a
      purple Fe(iii)-O-Trp chromophore-this alternative reactivity may affect human
      hypoxia sensing.

PMID- 18830488
TI  - Microgravimetric lectin biosensor based on signal amplification using
      carbohydrate-stabilized gold nanoparticles.
AB  - A highly sensitive microgravimetric lectin biosensor has been developed using
      carbohydrate-stabilized Au nanoparticles as a signal amplifier; mannose
      stabilized Au nanoparticles formed a sandwich-type complex with the target Con A
      specifically bound to a mannose-modified Au QCM electrode to give an amplified
      frequency response.

PMID- 18830489
TI  - trans-2-Aminocyclohexanol as a pH-sensitive conformational switch in lipid
      amphiphiles.
AB  - Protonation-induced conformational change of lipid tails is reported as a novel
      strategy to render pH-sensitive lipid amphiphiles and lipid colloids.

PMID- 18830490
TI  - Bulky 4-tritylphenylethynyl substituted boradiazaindacene: pure red emission,
      relatively large Stokes shift and inhibition of self-quenching.
AB  - Bulky 4-tritylphenylethynyl substituted boradiazaindacene with pure red emission,
      relatively large Stokes shift, high fluorescence quantum yield, and low self
      quenching was efficiently synthesized and qualified as a potential EL dopant.

PMID- 18830491
TI  - Diaryl ether synthesis in supercritical carbon dioxide in batch and continuous
      flow modes.
AB  - A high yielding, batch mode synthesis of diaryl ethers and sulfides by an S(N)Ar
      fluoride-mediated process in scCO(2) has been developed; the use of a polymer
      supported imidazolium fluoride reagent in batch mode led to the development of a
      fixed-bed continuous flow process, with high conversions.

PMID- 18830492
TI  - Fabrication of hydrophobic zeolites using triethoxyfluorosilane and their
      application as supports for TiO(2) photocatalysts.
AB  - Hydrophobically modified Y-zeolites were prepared by simple modification with
      triethoxyfluorosilane (TEFS). These zeolites, used as supports, enhanced the
      efficiency of deposited TiO(2) for the photocatalytic degradation of organics
      diluted in water.

PMID- 18830493
TI  - Up-conversion luminescent switch based on photochromic diarylethene and rare
      earth nanophosphors.
AB  - We have demonstrated a novel and unique route to a highly efficient luminescent
      switch with nondestructive readout capability by utilizing photochromic
      diarylethene and up-conversion LaF(3):Yb,Ho nanophosphors.

PMID- 18830494
TI  - Self-assembling squares with amino acid-decorated bipyridines: heterochiral self
      sorting of dynamically interconverting diastereomers.
AB  - Heterochiral self-sorting into only one stereoisomer is observed when metallo
      supramolecular squares self-assemble from amino acid-substituted, dynamically
      interconverting bipyridine stereoisomers and dpppM(OTf)(2) corners (M = Pd, Pt).

PMID- 18830495
TI  - Simplified syntheses of complex multifunctional nanomaterials.
AB  - Multifunctional probes are synthesized in a single step using peptide scaffold
      based multifunctional single-attachment-point (MSAP) reagents.

PMID- 18830496
TI  - Spectrally tunable uncaging of biological stimuli from nanocapsules.
AB  - This communication describes the first uncaging of stimuli in the far red,
      wavelengths that have much less of an adverse affect on cellular systems, via
      photolysis of photosensitized nanocapsules.

PMID- 18830497
TI  - Molecular rotors in hierarchically ordered mesoporous organosilica frameworks.
AB  - Diphenylene moieties, molecularly ordered in the framework of periodic mesoporous
      organosilicas, behave as molecular rotors and show a mobility with correlation
      times as short as a few nanoseconds.

PMID- 18830498
TI  - Polyacidic multiloading metal extractants.
AB  - Novel polynucleating, di- and tri-acidic ligands have been designed to increase
      the molar and mass transport efficiencies for the recovery of base metals by
      solvent extraction.

PMID- 18830499
TI  - Copper nanoparticles on hydrotalcite as a heterogeneous catalyst for oxidant-free
      dehydrogenation of alcohols.
AB  - We have developed a highly efficient heterogeneous catalytic system using
      hydrotalcite-supported Cu nanoparticles (Cu/HT) that can successfully promote the
      oxidant-free dehydrogenation of various alcohols under liquid-phase conditions.

PMID- 18830500
TI  - Use of a simple surface-active initiator in controlled/living free-radical
      miniemulsion polymerization under AGET and ARGET ATRP conditions.
AB  - This communication describes the first example of the efficient use of a simple
      amphiphilic molecule as both a surfactant and an initiator in the miniemulsion
      polymerization of methyl methacrylate under AGET and ARGET ATRP conditions.

PMID- 18830501
TI  - Gold-catalyzed efficient tandem assembly of terminal alkynes and arynes:
      synthesis of alkynylated biphenyl derivatives.
AB  - Gold catalysts have been found to catalyze the tandem assembly of arynes and
      terminal alkynes efficiently in the presence of CuI under mild reaction
      conditions to provide useful alkynylated biphenyl derivatives.

PMID- 18830502
TI  - Bromine-lithium exchange under non-cryogenic conditions: TMSCH(2)Li-LiDMAE
      promoted C-2 lithiation of 2,3-dibromopyridine.
AB  - The first C-2 selective bromine-lithium exchange in 2,3-dibromopyridine was
      performed at 0 degrees C in toluene using the TMSCH(2)Li-LiDMAE reagent.

PMID- 18830503
TI  - Synthesis of highly phenylene substituted p-phenylene oligomers from pyrylium
      salts.
AB  - A transition metal free route to phenyl substituted oligophenylenes that
      tolerates halogens is described.

PMID- 18830504
TI  - Gold nanoparticles synthesis and stabilization via new "clicked"
      polyethyleneglycol dendrimers.
AB  - Gold nanoparticles (AuNPs) are synthesized and stabilized by new "clicked"
      dendrimers of generations zero to two (G(0)-G(2)) containing tri- and tetra
      ethyleneglycol tethers; they are either encapsulated by G(1) (81 tethers) and
      G(2) (243 tethers) or stabilized without encapsulation by G(0) (27 tethers).

PMID- 18830505
TI  - A C-H activation-CO(2)-carboxylation reaction sequence mediated by an
      'Iridium(dppm)' species. Formation of the anionic ligand (Ph(2)P)(2)C-COOH.
AB  - The reaction of [Ir(2)(mu-Cl)(2)(coe)(4)] with 1,1-bisdiphenylphosphinomethane
      under CO(2) atmosphere affords the complex [IrCl(dppm)(H){(Ph(2)P)(2)C-COOH}](2)
      by initial CH activation followed by formal insertion of CO(2) into the C-H bond
      of the formed diphosphanylmethanide ligand.

PMID- 18830506
TI  - Specific interactions between silver(I) ions and cytosine-cytosine pairs in DNA
      duplexes.
AB  - Very specific binding of the Ag(i) ion unexpectedly stabilized DNA duplexes
      containing the naturally occurring cytosine-cytosine (C-C) mismatch-base pair;
      because the C-C pair selectively binds to the Ag(i) ion, we developed a DNA-based
      Ag(i) sensor that employed an oligodeoxyribonucleotide containing C-C pairs used
      for Ag(i) binding sites.

PMID- 18830507
TI  - Interaction of trivalent antimony with a CCHC zinc finger domain: potential
      relevance to the mechanism of action of antimonial drugs.
AB  - Sb(III) competes with Zn(II) for its binding to the CCHC zinc finger domain of
      the NCp7 protein of HIV-1, indicating that zinc finger proteins may be targets
      for antimony-based drugs and thus responsible for their important pharmacological
      actions.

PMID- 18830508
TI  - Development of fluorescent aryltryptophans by Pd mediated cross-coupling of
      unprotected halotryptophans in water.
AB  - A convenient and high yielding procedure for the Suzuki-Miyaura cross-coupling of
      unprotected bromo- and chlorotryptophans in water provides fluorescent
      aryltryptophans.

PMID- 18830509
TI  - Utilisation of an eta(3)-allyl hydride complex, formed by UV irradiation, as a
      controlled source of 16-electron (eta(5)-C(5)Me(5))Rh(CH(2)[double bond, length
      as m-dash]CHMe).
AB  - Low temperature UV irradiation of solutions of (eta(5)-C(5)Me(5))Rh(CH(2)[double
      bond, length as m-dash]CHMe)(2) yields (eta(5)-C(5)Me(5))Rh(eta(3)
      CH(2)CHCH(2))(H), which provides controlled access to the 16-electron fragment
      (eta(5)-C(5)Me(5))Rh(CH(2)[double bond, length as m-dash]CHMe).

PMID- 18830510
TI  - Metal-catalyzed reaction of N-(2-indolyl)methyl, N-bis(trimethylsilyl)methyl
      diazoamides: an entry into the beta-carboline ring system.
AB  - The intramolecular metal-catalyzed reaction of N-(2-indolyl)methyl, N
      bis(TMS)methyl diazoamides proceeds with high conformational control and
      chemoselectivity to give cyclopropyl derivatives, which rearrange to beta
      carboline products.

PMID- 18830511
TI  - A catalytic highly enantioselective direct synthesis of 2-bromo-2-nitroalkan-1
      ols through a Henry reaction.
AB  - Highly enantiomerically enriched 2-bromo-2-nitroalkan-1-ols are prepared by
      direct condensation of aliphatic and aromatic aldehydes with bromonitromethane in
      the presence of a catalytic amount of copper(ii) acetate and a C(1)-symmetric
      camphor-derived amino pyridine ligand.

PMID- 18830512
TI  - Prevalence of mouth breathing among children.
AB  - OBJECTIVE: To determine the prevalence of mouth breathing among children aged 3
      to 9 years living in the urban districts of the town of Abaete, MG, Brazil.
      METHODS: This study assesses a representative, randomized sample of the town's
      population (23,596 inhabitants). Children were selected by lots according to a
      random number table until 370 had been enrolled; this number had been determined
      by statistical calculation. A protocol for anamnesis and clinical assessment of
      the patients was specially developed for this project, since no preexisting
      instruments could be found in the literature that had been validated and were
      appropriate for the purpose. Data were analyzed using SPSS version 10.5. RESULTS:
      The prevalence of mouth breathing was found to be 55%, or 204 children.
      CONCLUSION: Further studies are needed to validate a questionnaire for the
      clinical diagnosis of mouth breathers at the primary care level.

PMID- 18830513
TI  - Home medicine chests and their relationship with self-medication in children and
      adolescents.
AB  - OBJECTIVE: To investigate the contents of home medicine chests and their
      relationship with self-medication in children and adolescents in the towns of
      Limeira and Piracicaba, SP, Brazil. METHODS: This is a descriptive population
      study based on a home survey of a simple random sample from both towns,
      comprising 705 households from census sectors selected by means of cluster
      sampling. INCLUSION CRITERIA: age <or= 18 years; an obligatory interview with at
      least one guardian; inventory of medicines kept at home; and having taken at
      least one medication during the 15 days prior to the interview. The participants
      were split into two groups based on medication: self-medication (lay advice) and
      medical prescription. Tests of linear association were performed, in addition to
      a descriptive analysis of the variables and multiple logistic regression.
      RESULTS: A total of 3,619 medicines were found (mean = 5.1/household; 79.6% were
      pharmaceutical preparations). The rooms most commonly used to store medications
      were bedrooms (47.5%), kitchens (29.9%), and bathrooms (14.6%); 76.5% were in
      cardboard boxes and within easy reach of 142 children aged <or= 6 years. Taking
      the pharmaceutical preparations in isolation (n = 2,891), the most common were
      analgesics/antipyretics (26.8%) and systemic antibiotics (15.3%), and the self
      medication group had significantly larger stocks of these medications (p < 0.01).
      Storing medications in the bathroom (odds ratios = 1.59) and legal guardians with
      <or= 4 years of primary education (odds ratios = 2.40) indicated greater risk of
      self-medication. CONCLUSIONS: Keeping medicines at home is a common practice, and
      it is important to implement campaigns to encourage rational use, reduced waste
      and safe storage of medicines.

PMID- 18830514
TI  - Newborn screening: what pediatricians should know.
AB  - OBJECTIVE: To review the literature on the current situation of neonatal
      screening worldwide and in Brazil. To define the role of pediatricians in
      neonatal screening programs. SOURCES: Scientific articles selected by means of
      searches run on the medical websites MEDLINE, Cochrane, PubMed (MeSH) and MD
      Consult, using the keywords newborn screening, neonatal, pediatrics, diagnosis,
      primary care, ethics and their equivalents in Portuguese, in isolation and in
      combination, in addition to medical textbooks on genetics and inborn errors of
      metabolism, published between January 1998 and December 2007, the National
      Neonatal Screening Program technical standards and routines manual, and Ministry
      of Health decree 822/2001. SUMMARY OF THE FINDINGS: Published data demonstrate a
      great diversity in the number of diseases included in the neonatal screening
      programs of different countries. In Brazil, the National Neonatal Screening
      Program was set up in 2001, to screen for phenylketonuria, congenital
      hypothyroidism, sickle-cell anemia and cystic fibrosis. Screening for a wider
      range of conditions using mass spectrometry is currently the subject of
      disagreement and discussion of financial and ethical issues. CONCLUSIONS:
      Neonatal screening is one of the most important advances for the prevention of
      pediatric diseases. Nevertheless, implementation is complex, multidisciplinary
      and dependent on public health policies and, to date, there is no consensus on
      which diseases should be included. A large number of scientific and ethical
      questions need to be discussed in order to better define the screening panels to
      be implemented. Pediatricians have important roles to play in all stages of
      neonatal screening programs.

PMID- 18830515
TI  - Natural killer cells and immune surveillance.
AB  - OBJECTIVES: To analyze the importance of natural killer cells, their killer
      immunoglobulin-like receptors (KIR) and genes in autoimmunity and in the immune
      surveillance against infectious agents and stem cells transplantation. The
      characteristics and polymorphisms of the KIR genes and receptors in the Brazilian
      population is described. SOURCES: Textbooks, review articles and recent
      scientific articles are cited and listed in the references. SUMMARY OF THE
      FINDINGS: KIR genes and haplotypes within a Brazilian Caucasian population were
      surveyed and analyzed to assess the future relationship of this system with
      diseases. Of 116 voluntary bone marrow donors, we identified 32 genotypes with
      frequencies of A and B haplotypes of 51 and 49%, respectively. A comparative
      analysis was performed between these genotypes and those from other populations.
      CONCLUSIONS: Innate immunity is an important anti-infectious barrier in newborns.
      It is independent of both cellular and humoral immunity, can be faster and
      confers great advantage in early age. At the same time, it stimulates CD8 T
      lymphocytes to act and amplify the immunological protection network.
      Nevertheless, as in the majority of situations in which immunity is activated, it
      can also be harmful, damaging the body through autoimmune mechanisms or even,
      through its absence, creating space for infectious agents to act free. Our study
      of a control group for KIR genotype and haplotypes in Brazilian Caucasoids could
      be used in future analyse of diseases related to these genes.

PMID- 18830516
TI  - Leukemia: genetics and prognostic factors.
AB  - OBJECTIVE: To present the implications of genetics, particularly of cytogenetic
      techniques, for the diagnosis and prognosis of leukemia. SOURCES: A survey of
      articles selected from MEDLINE, American Society of Hematology educational
      programs, the CAPES web portal, the National Comprehensive Cancer Network and
      textbook chapters. SUMMARY OF THE FINDINGS: Since the discovery in 1960 by Peter
      C. Nowel and David Hungerford of the 9:22 translocation (the Philadelphia
      chromosome), genetics has come to play an important role in hematology, in this
      case making it possible to diagnose chronic myeloid leukemia and opening doors to
      research avenues for the whole field of oncology. One point of great interest
      refers to the implications of these findings for the prognosis of a range of
      types of leukemia. In acute myeloid leukemia, the karyotype is of fundamental
      importance to postremission treatment decisions, and molecular factors determine
      the treatment of individuals with normal karyotypes. In chronic myeloid leukemia,
      clonal evolution is associated with progression to the blast crisis. Patients on
      imatinib who cease responding may have mutations on their ABL gene. Finally, in
      acute lymphoblastic leukemia, factors such as hyperdiploidy and t 12:21 are
      associated with good prognosis, whereas carriers of t 4:11 and t 9:22 are
      considered high risk patients. CONCLUSIONS: Genetics has come to stay as far as
      hematology and, in particular, the management of leukemia and its prognostic
      factors are concerned. These tests should always be carried out and the
      appropriate treatment adopted in the light of their results, so that optimal
      patient outcomes can be achieved.

PMID- 18830517
TI  - Ethics, genetics and pediatrics.
AB  - OBJECTIVES: To reflect on the nature of ethics, from a contemporary perspective,
      and also on which features of the family relationship have an impact on the
      interface between genetics and pediatrics. SOURCES: The data used are the fruit
      of the authors' own intellectual production plus other bibliographic references.
      SUMMARY OF THE FINDINGS: Genetics has presented ethics with new challenges.
      Particularly in pediatrics, where caring for patients is almost indivisible from
      a continuous relationship with their families, these issues are amplified even
      further, generating new questions that health professionals have not previously
      had to face. CONCLUSIONS: Based on the reflections outlined here, emphasis can be
      placed on the importance of actively recognizing the Other in its multiple
      dimensions and on the repercussions that this perspective has for the physician
      patient-family relationship.

PMID- 18830518
TI  - Genetics: an essential tool for the pediatrician of the 21st century.

PMID- 18830519
TI  - Asthma Programme in Finland: the quality of primary care spirometry is good.
AB  - AIMS: To assess the quality of primary care spirometry by visual inspection of
      the flow-volume expiratory curve and to study the quantity of clinical
      information provided on the spirometry report sheets. METHODS: Retrospective
      audit of 868 expiratory flow-volume curves referred to three pulmonary clinics
      assessed against five predefined quality criteria. Clinical information included
      on the spirometry report sheets was also collected. RESULTS: Quality was good in
      78% of pre-bronchodilation curves and in 80% of post-bronchodilation curves.
      Obtaining a sharp PEF value and full vital capacity exhalation seemed to be the
      critical points of measurement. Inter-rater reliability of the curve assessment
      was mainly good. Data on where the spirometry took place, and comments on the use
      of respiratory medication and patient co-operation were often lacking.
      CONCLUSIONS: The quality of primary care spirometry was good. Adequate clinical
      information on the report sheets would further improve the quality of this
      diagnostic process.

PMID- 18830520
TI  - How frequently are physiological variables recorded in the emergency room in
      patients with obstructive pulmonary diseases and pneumonia?
AB  - AIM: To assess how frequently measurements of relevant physiological variables
      are made in patients presenting acutely to hospital with obstructive pulmonary
      diseases (OPD) and pneumonia. METHODS: Patients admitted to three hospitals in
      western Norway with OPD (asthma or chronic obstructive pulmonary disease (COPD))
      and/or pneumonia over a 75-day period were included in the study. The assessing
      physicians in the emergency room (ER) were asked to measure and record
      physiological variables according to normal practice. RESULTS: There were 338
      patients (54% women), with an average age of 64 (SD 19) years. The initial
      diagnoses were OPD (176), pneumonia (103) and a combination of OPD and pneumonia
      (59). Heart rate and body temperature were recorded in almost all patients,
      whereas the recording of all other variables varied from 45% to 91%. Most
      variables were recorded more frequently in OPD than in pneumonia. CONCLUSIONS:
      The importance of recording respiratory rate, cutaneous oxygen saturation, and
      peak expiratory flow should be stressed in the training of physicians.

PMID- 18830521
TI  - The use of microspirometry in detecting lowered FEV1 values in current or former
      cigarette smokers.
AB  - AIMS: COPD is an underdiagnosed disease. This study was undertaken to assess the
      value of microspirometry in detecting reduced FEV1 values in cigarette smokers,
      i.e., subjects at high risk for COPD. METHODS: A total of 611 smokers or ex
      smokers with a smoking history >20 years and no previously-diagnosed lung disease
      were recruited (389 male, age 27-83 years, mean age 56 years, mean smoking
      history 35 pack years, 19% ex-smokers). RESULTS: An FEV1 < 80% predicted on
      microspirometry was found in 44.6% of cases. The mean FEV1 was 2.8 litres (80.6%
      predicted, range 26-121%). This correlated well with values obtained from full
      spirometry (R=0.965, p<0.0001). Detailed questionnaire responses revealed that
      almost half of the subjects (48.2%) reported chronic cough and sputum production
      and 39.8% reported breathlessness during exercise. CONCLUSIONS: Microspirometry
      finds a considerable number of smokers or ex-smokers with reduced FEV1 values.
      Microspirometry is quick to perform. All smokers with reduced microspirometry
      FEV1 values would benefit from smoking cessation, and all patients with reduced
      FEV1 values need to be considered for full spirometry to confirm if they actually
      have COPD.

PMID- 18830522
TI  - Management of asthma in Australian general practice: care is still not in line
      with clinical practice guidelines.
AB  - OBJECTIVE AND BACKGROUND: We investigated the quality of primary care asthma
      management in a sample of Australian general practices. METHODS: 247 general
      practitioners (GPs) from 97 practices completed a structured interview about
      management of asthma, diabetes and hypertension/heart disease. A further
      structured interview with the senior practice principal and practice manager was
      used to collect information about practice capacity for chronic disease
      management. RESULTS: Just under half of GPs (47%) had access to an asthma
      register and the majority (76%) had access to spirometry in their practice. In
      terms of routine management of asthma, 12% of GPs reported using spirometry
      routinely, 13% routinely reviewed written asthma action plans, 27% routinely
      provided education about trigger factors, 30% routinely reviewed inhaler
      technique, 24% routinely assessed asthma severity, and 29% routinely assessed
      physical activity. Practice characteristics such as practice size (p=1.0) and
      locality (rural/metropolitan) (p=0.7) did not predict quality of asthma
      management nor did indicators of practice capacity including Business maturity,
      IT/IM maturity, Multidisciplinary teamwork, and Clinical linkages. CONCLUSION:
      Gaps remain in the provision of evidence-based care for patients with asthma in
      general practice. Markers of practice capacity measured here were not associated
      with guideline-based respiratory care within practices.

PMID- 18830523
TI  - Burkholderia pseudomallei meningitis following inadequate treatment of
      melioidotic mycotic aneurysm.
AB  - We report a 64-year-old man presenting with meningitis caused by Burkholderia
      pseudomallei predisposed by persistent aortic graft infection following
      inadequate treatment of a melioidotic mycotic aneurysm. The relapse of
      melioidosis presenting as acute meningitis is a unique event. Successful
      treatment of deep-seated melioidosis can only be achieved when robust
      antimicrobial therapy is combined with appropriate surgical debridement.

PMID- 18830524
TI  - Granulomatous gastritis: a diagnostic dilemma?
AB  - Granulomatous inflammation of the gastrointestinal tract is an uncommon entity;
      an aetiopathogenic diagnosis can be reached only by combining the morphological
      examination with clinical and laboratory investigations. We report two cases of
      granulomatous gastritis: a 27-year-old woman presenting with weight loss and a 55
      year-old woman presenting with epigastric pain and vomiting. Upper
      oesophagastroduodenoscopy in these cases showed antral hyperaemia and
      histopathology showed non-caseating gastric granulomatous inflammation. Both the
      cases were extensively worked-up for possible tuberculosis (TB) as the patients
      lived in an endemic area, before starting steroids for the possibility of Crohn's
      disease (CD) . The first patient improved but the second patient had a flare of
      underlying undiagnosed TB. Granulomatous gastritis present a diagnostic challenge
      for treating physicians because of similar clinical, laboratory and endoscopical
      features between CD and intestinal TB.

PMID- 18830525
TI  - Vasopressin for the management of catecholamine-resistant anaphylactic shock.
AB  - Severe anaesthetic anaphylaxis is relatively uncommon. Oxygen, fluids and
      epinephrine are considered to be the mainstay for treatment of cardiovascular
      collapse and current guidelines for the management of anaphylaxis list only
      epinephrine as a vasopressor to use in the event of a cardiovascular collapse.
      Recently, evidence has emerged in the support of the use of vasopressin in
      cardiopulmonary resuscitation; it is also recommended for the treatment of
      ventricular fibrillation, septic shock and post-cardiopulmonary bypass
      distribution shock. Currently, there is no algorithm or guideline for the
      management of anaphylaxis that include the use of vasopressin. We report a 24
      year-old woman who developed severe anaphylactic shock at induction of
      anaesthesia while undergoing laparoscopic cholecystectomy. Circulation shock was
      refractory to epinephrine and high doses of pure alpha-agonist phenylephrine and
      norepinephrine. Single intravenous dose of two units of vasopressin re
      established normal circulation and blood pressure.

PMID- 18830526
TI  - Mandibular osteomyelitis and multiple skeletal complications in Albers-Schonberg
      disease.
AB  - Albers-Schonberg disease, or autosomal dominant osteopetrosis type II, is the
      most common form of the rare disease, osteopetrosis. Mandibular osteomyelitis is
      a rare complication of the disease. A host of other skeletal complications may
      also occur. Mandibular osteomyelitis along with bilateral severe coxa vara and
      pars fracture is very rare in Albers-Schonberg disease. We present the occurrence
      of these complications in a 24-year-old man with Albers-Schonberg disease. His
      mandibular osteomyelitis was successfully treated.

PMID- 18830527
TI  - Bilateral tarsometatarsal fracture-dislocations: a missed work-related injury.
AB  - Tarsometatarsal (Lisfranc) fracture-dislocation is an uncommon foot injury.
      Subtle injuries are more difficult to diagnose though they cause serious
      morbidity. Bilateral subtle tarsometatarsal injury has not been reported before.
      We report bilateral subtle tarsometatarsal dislocations that were caused by a
      work-related accident in a 25-year-old man. The injury was initially missed.
      Diagnosis was confirmed by computed tomography with curved reconstruction.
      Associated foot injuries are shown as a guide to the diagnosis.

PMID- 18830528
TI  - Adrenal cavernous haemangioma.
AB  - The adrenal gland is a rare location for haemangioma. Approximately 52 surgical
      cases have been reported in the literature. We report a huge non-functioning
      adrenal haemangioma presenting in a 50-year-old woman with flank pain. This was
      illustrated by computed tomography. It was surgically removed and diagnosed
      postoperatively as adrenal haemangioma. Although rare, adrenal haemangioma should
      be included in the differential diagnosis of adrenal neoplasms. The risks of
      haemorrhage, necrosis and thrombosis impose in the majority of cases surgical
      excision, particularly in tumours more than 3 cm in diameter.

PMID- 18830529
TI  - Unusual mode of firearm injury from the recoiled rear end of a gun barrel.
AB  - Atypical gunshot wounds are caused by a diverse set of parameters relating to
      weapons and ammunition. We report a previously-unreported and atypical mode of
      gunshot wound produced by a detached rear end of the barrel of a gun following
      accidental gun fire, and discuss the difficulties in the management. A 36-year
      old man presented to the emergency department with an alleged history of injury
      on the forehead with the rear end of a gun barrel following accidental gunfire
      while cleaning the nozzle. Since the time of injury, the patient was in an
      altered sensorium and had weakness on the right side of the body. There was
      minimal but continuous bleeding from the wound, with extrusion of brain matter.
      Skull radiograph showed that the rear end of the barrel had entered the left
      frontal bone, with associated depressed fracture of the frontal bone. The patient
      underwent a bicoronal, bifrontal craniotomy with a T-shaped extension towards the
      barrel to facilitate the reflection of the scalp flap and to avoid any movement
      of the barrel as it might further injure the brain. Necrotic brain, dura and bone
      pieces were removed. The patient was doing well at follow-up except for mild
      residual motor deficits. This case illustrates that while working with limited
      facilities, particularly in underdeveloped countries, a careful clinical
      assessment, interpretation of available images and a judicious operative approach
      can help to save the patient.

PMID- 18830530
TI  - Oesophageal duplication cyst: an unusual cause of retrosternal pain and dysphagia
      in an adult.
AB  - Oesophageal duplication cysts in adults are a rare entity and are mostly
      asymptomatic. We describe the imaging findings in a rare case of oesophageal
      duplication cyst simulating cold abscess, causing retrosternal pain and dysphagia
      in a 25-year-old man.

PMID- 18830531
TI  - An atypical anatomical variation of palmar vascular pattern.
AB  - A complex variation in the pattern of blood supply to the palm of the hand was
      encountered during a routine dissection of a female adult cadaver. Findings were:
      (a) there was no communication between the superficial palmar branches of the
      radial and ulnar arteries (incomplete superficial palmar arch); (b) the
      superficial palmar branch of the radial artery coursed superficially to the
      thenar muscles supplying two common palmar digital arteries for adjacent sides of
      the thumb and index finger, thereby replacing the conventional arteria radialis
      indices; (c) the branch supplying the lateral side of the thumb was seen arising
      from the deep branch of the radial artery; (d) the superficial palmar branch of
      the ulnar artery supplied a branch to the medial side of the little finger, and
      two common palmar digital arteries for the adjacent sides of the little and ring
      fingers and ring and middle fingers, respectively. Familiarity with the
      variations in the vascular patterns resulting from a number of developmental
      errors remains the crucial issue for personnel engaged in reconstructive hand
      surgery, where these varied patterns act as pivotal points around which
      successful accomplishment of various advanced surgical procedures revolve.

PMID- 18830532
TI  - Cystogastrocolic fold and associated atrophy of the gallbladder.
AB  - Peritoneal anomalies are common in humans. We report the presence of a
      cystogastrocolic fold associated with an abnormally small gallbladder in a 50
      year-old male cadaver. Presence of this fold is one of the clinically important
      anomalies, which can result in atrophy of the gallbladder or congenital
      obstruction of the duodenum.

PMID- 18830533
TI  - Twisted renal vessels producing an abnormal shape of the right kidney.
AB  - The kidneys and the renal vessels are subject to a wide variety of variations. We
      report a rare variation of the right kidney and right renal vessels in a 60-year
      old male cadaver. The right kidney was pyramidal in shape and the hilum was
      directed anteriorly. The right renal vessels were twisted against each other, and
      the inferior vena cava had a kink to the right side. Knowledge of this variation
      may be useful for the nephrologists, radiologists and surgeons.

PMID- 18830534
TI  - Multiple accessory structures in the upper limb of a single cadaver.
AB  - The arterial and muscular variations of the upper limbs are common but important
      with regard to surgical approaches. Even though anomalies of the coracobrachialis
      muscle are rare, anatomical variations of the biceps brachii, existence of the
      accessory muscles in the forearm and persistent median artery are known and well
      documented. During routine dissection, we observed some important anatomical
      variations in a 50-year-old male cadaver. The variations were unilateral. The
      anomalies were: third head for biceps brachii muscle, an accessory belly for
      coracobrachialis muscle crossing the median nerve and brachial vessels and
      continuing with the medial head of triceps brachii muscle to be inserted to the
      olecranon process (coracoulnaris), a persistent median artery and an additional
      muscle in the anterior compartment of forearm. Although there are individual
      reports about these variations, the combination of these variations in one
      cadaver has not previously been described in the literature. Awareness of these
      variations is necessary to avoid complications during radiodiagnostic procedures
      or surgeries in the upper limb.

PMID- 18830535
TI  - Mandatory vaccination: is it the future reality?

PMID- 18830536
TI  - Emil Theodor Kocher (1841-1917): thyroid surgeon and Nobel laureate.

PMID- 18830537
TI  - Abstract and keywords.
AB  - The abstract of a scientific paper represents a concise, accurate and factual
      mini-version of the paper contents. Abstract format may vary according to the
      individual journal. For original articles, a structured abstract usually consists
      of the following headings: aims (or objectives), materials and methods, results
      and conclusion. A few keywords that capture the main topics of the paper help
      indexing in the medical literature.

PMID- 18830538
TI  - Optic neuritis in Singapore.
AB  - INTRODUCTION: Optic neuritis (ON) is the commonest optic neuropathy encountered
      in the younger group of patients from the Singapore Neuro-Ophthalmology Study
      Group. Previous surveys in Asia and our study suggest that ON in Singapore
      differs from that in Western populations where the majority of cases are
      associated with multiple sclerosis (MS). METHODS: Patients satisfying our entry
      criteria for ON seen between September 2002 and June 2004 were enrolled in the
      study. The data collected was recorded in a central database and analysed two
      years later. RESULTS: The majority (60 percent) of our patients had anterior ON
      with optic disc swelling (papillitis), were idiopathic in 49.1 percent, and
      associated with MS in only 25.5 percent. Bilateral cases comprised 16.4 percent
      of our series and were usually of the anterior variety and mostly idiopathic,
      although it is still essential to rule out secondary causes. Recurrent ON is
      indicative of an underlying disease process. CONCLUSION: The pattern of ON as
      seen in Singapore differs from that reported in Caucasian studies and from the
      seminal Optic Neuritis Treatment Trial. We found a higher incidence of optic disc
      swelling, i.e. anterior ON (papillitis), and a lesser association with MS; visual
      recovery is similarly good but our recurrence rate is lower.

PMID- 18830539
TI  - Continuous figure-of-eight suturing in upper and lower gastrointestinal
      anastomosis.
AB  - INTRODUCTION: The optimal technique for gastrointestinal anastomosis is
      controversial. The three most popular techniques are two layers, one layer and
      the stapling method. However, there is no universal agreement on the best
      technique. The aim of this study was to evaluate the safety, feasibility, and
      efficacy of continuous figure-of-eight suturing in gastrointestinal anastomosis.
      METHODS: This was a retrospective study of 170 patients who underwent
      gastrointestinal anastomosis using continuous figure-of-eight suturing for the
      first layer and continuous seromuscular suturing for the second layer from August
      1993 to January 2006. All operations were performed by a single consultant
      surgeon. We assessed each anastomosis by checking the integrity, vascularity and
      patency, and also ensuring tension-free status. Postoperatively, patients were
      managed by routine care of intravenous fluids and nasogastric tube until they had
      active bowel sounds and started absorbing. Imaging was arranged for patients who
      developed clinical signs and symptoms of leak. RESULTS: 170 patients underwent
      gastrointestinal anastomosis by continuous figure-of-eight suturing for different
      pathologies over a two-and-a-half-year period. There were 92 (54.1 percent) men
      and 78 (45.9 percent) women. The mean age of the patients was 56 (range 20-88)
      years. The median follow-up was 74 months. There were 124 (72.9 percent) small
      bowel anastomosis and 46 (27.1 percent) large bowel anastomosis. An important
      complication after gastrointestinal anastomosis was leakage, which was reported
      in three (1.8 percent) patients. One of them had gastric cancer, one had Crohn's
      disease and one had intestinal ischaemia. No mortality was reported in relation
      to anastomotic failure. Two (1.2 percent) patients developed stenosis and 15 (8.8
      percent) patients died because of progression of their disease or other
      pathologies during the follow-up. CONCLUSION: Continuous figure-of-eight suturing
      is a simple, easy to learn, safe and satisfactory upper and lower
      gastrointestinal anastomosis technique.

PMID- 18830540
TI  - Arthroscopic Bankart repair for traumatic anterior shoulder instability with the
      use of suture anchors.
AB  - INTRODUCTION: The arthroscopic method offers a less invasive technique of Bankart
      repair for traumatic anterior shoulder instability. The results continue to
      improve with the advancements made in instrumentation and technique. This study
      aims to evaluate the outcome of arthroscopic Bankart repair with the use of
      suture anchors for cases that were followed-up for at least two years from the
      date of surgery. METHODS: This was a consecutive series of 40 shoulders in 37
      patients who underwent arthroscopic Bankart repair with suture anchor. The mean
      age at the time of operation was 26.3 years. The patients were assessed with two
      different outcome measurement tools (the University of California at Los Angeles
      [UCLA] shoulder rating scale and simple shoulder test [SST] score). The mean
      duration of follow-up was 30.2 months. The recurrence rate, range of motion, and
      postoperative function were evaluated. RESULTS: The two shoulder scores
      significantly improved after surgery (p-value is less than 0.05). According to
      the UCLA scale, 37 shoulders (92.5 percent) had excellent or good scores, one
      shoulder (2.5 percent) had a fair score, and two (five percent) had poor scores.
      All 12 components of SST showed improvement, which was statistically significant.
      Overall, the rate of postoperative recurrence was 7.5 percent (three shoulders).
      All patients either maintained or demonstrated improvement of range of motion.
      There was no loss of external rotation range of motion postoperatively.
      CONCLUSION: Arthroscopic Bankart repair with the use of suture anchors is a
      reliable treatment method that can provide a good clinical outcome with excellent
      postoperative shoulder motion and low recurrence rate.

PMID- 18830541
TI  - Patients with chronic hepatitis B infection: what is their quality of life?
AB  - INTRODUCTION: Hepatitis B (HBV) is endemic in Singapore. This study aimed to
      determine the quality of life of patients with chronic HBV infection (HBV
      carriers) on conservative management. They were reviewed in primary care
      facilities and in a district hospital in Singapore. METHODS: This cross-sectional
      survey utilised a validated Hepatitis Quality of Life questionnaire, which
      incorporated the SF-36 health survey, to assess a convenience sample of HBV
      carriers' quality of life in 14 domains. The mean scores in each domain were
      determined, with higher scores indicating better health. Wilcoxon-Mann-Whitney
      test was used in the data analysis to determine statistical significance (p-value
      is less than 0.05). RESULTS: The mean age of 108 participants was 44.1 (standard
      deviation 12.5) years. They were predominantly Chinese (90.7 percent), male (58.3
      percent) and 50.7 percent of them had family members who were HBV-infected. The
      latter had higher scores in the hepatitis specific limitation (HLIM) domain. The
      majority did not have any impaired physical nor mental health. In comparison with
      the healthy peers in the local population, the Chinese HBV carriers scored
      significantly lower in the "social functioning" domain (p-value is less than
      0.001), regardless of gender. CONCLUSION: The majority of HBV carriers had good
      physical and mental health. Physicians should recognise the impact of the chronic
      infection on the social aspects of daily living of the HBV carriers, and such
      issues should be addressed appropriately to provide better quality care.

PMID- 18830542
TI  - Prevalence and risk factors of anti-tuberculosis drug-induced hepatitis in
      Malaysia.
AB  - INTRODUCTION: Tuberculosis (TB) affects one-third of the world's population. Anti
      TB drugs with isoniazid, rifampicin and pyrazinamide are very effective but they
      can cause hepatotoxicity. Many risk factors have been recognised. Data on
      prevalence of anti-TB drug-induced hepatitis as well as the contributing risk
      factors are scarce in Malaysia. This observational case control study was
      designed to look at the prevalence and the risk factors of drug-induced hepatitis
      in our population. METHODS: We retrospectively examined all the case notes of
      anti-TB drug-induced hepatitis over a 30-month period from January 2003 to June
      2005. They were compared with controls selected by simple random sampling. Both
      groups were compared in terms of demographical data and risk factors, such as
      age, gender, body mass index, hepatitis B carrier, human immunodeficiency virus
      (HIV) infection, sites of TB, and pretreatment liver biochemistries (serum
      albumin, globulin, aspartate aminotransferase, alanine aminotransferase and
      bilirubin). Data was evaluated by chi square, independent t-test (univariate) and
      binary logistic regression analysis (multivariate). RESULTS: Out of 473 TB
      patients, 46 developed hepatitis and 138 were selected as controls. The
      prevalence of drug-induced hepatitis was 9.7 percent. On univariate analysis, HIV
      infection (p-value is 0.005), extrapulmonary tuberculosis (p-value is 0.008),
      lower serum albumin (p-value is 0.023) and higher serum globulin (p-value is
      0.025) were significant risk factors. On binary logistic regression, only HIV
      infection (p-value is 0.018) and extrapulmonary TB (p-value is 0.017) were
      significant. CONCLUSION: The prevalence of hepatitis was 9.7 percent. The
      presence of HIV infection and extrapulmonary TB were significant risk factors for
      the development of hepatitis.

PMID- 18830543
TI  - Maternal deaths from suicide in Singapore.
AB  - INTRODUCTION: Maternal mortality in Singapore, as in other developed countries,
      has remained low in the past decade. In the United Kingdom and Australia,
      maternal deaths from suicide and psychiatric causes have been the leading cause
      of maternal mortality, and there have therefore been comprehensive healthcare
      programmes to address the mental health needs of mothers. METHODS: In this study,
      we looked at maternal deaths from 2000 to 2004, by linking coronial cases of
      female suicide in the reproductive age group 15-45 years, with the birth
      registration database, to identify both early and late maternal deaths. RESULTS:
      There was only one identified maternal death among 589 female suicides aged 15-45
      years, occurring in a teenager within the first month postpartum. There was
      likely also another case that was unconfirmed and unreported. CONCLUSION: From
      this preliminary study, suicide and psychiatric causes are not significant causes
      of maternal mortality in Singapore. However, given that the epidemiology of
      postnatal depression statistics mirror that of the other countries, it is
      possible that maternal suicides have been underreported, and the load may well be
      higher. There is a need for a similar confidential enquiry into maternal deaths
      to be set up here, as is already in place in various countries, notably the
      United Kingdom and Australia, for the past decade.

PMID- 18830544
TI  - Expectant versus aggressive management in severe preeclampsia remote from term.
AB  - INTRODUCTION: Our study aims to compare neonatal and maternal outcomes between
      expectant (or conservative) and aggressive (or immediate) management in cases
      with severe preclampsia remote from term. METHODS: This is a comparative study
      conducted at Al-Batool Teaching Hospital in Mosul City, Iraq, from April 2003 to
      August 2004. A total of 74 singleton pregnancies complicated by severe
      preeclampsia with gestational age of 24-34 weeks were studied during this period.
      The criteria used for the diagnosis of severe preeclampsia were in accordance
      with the guidelines of the American College of Obstetricians and Gynaecologists.
      All the patients were counselled for expectant management. 39 patients were
      delivered immediately due to refusal of expectant management either by the
      patient or the attending physician. The other 35 patients were managed
      expectantly; this group was followed-up and carefully monitored for a period
      ranging from 72 hours to 18 days. Neonatal parameters, neonatal outcome and
      maternal outcome were compared between the two groups. RESULTS: The mean value of
      pregnancy prolongation was 9.2 days. Median gestational age for the first group
      was 29 weeks, and for the second group, it was 30 weeks. Regarding neonatal
      parameters, the expectantly-managed group had a higher Apgar score at one minute
      (3.56 +/- 1.72 vs. 5.05 +/- 1.77, p-value equals 0.001), lower mean days of
      hospitalisation in the neonatal intensive care unit (6.83 +/- 5.38 vs. 4.50 +/-
      3.46, p-value equals 0.03), with a lower incidence of neonatal and maternal
      complications. CONCLUSION: Expectant management is recommended in patients with
      severe preeclampsia remote from term, after proper selection of patients and
      careful monitoring.

PMID- 18830545
TI  - Cutaneous endometriosis.
AB  - INTRODUCTION: Cutaneous or subcutaneous endometriosis is a rare entity that is an
      often overlooked because of chronic abdominal pain. METHODS: We reviewed the ten
      cases of cutaneous endometriosis that presented to this hospital over a seven
      year period. RESULTS: The mean age of patients at presentation was 36.3 years.
      All our patients presented with cyclical abdominal pain. There was a considerable
      delay in the diagnosis and offer of treatment, the mean length of time between
      onset of symptoms to surgery being 31.7 months (range 1-62 months). The onset was
      spontaneous in 40 percent of our patients and the rest had scar endometriosis.
      The patients with spontaneous onset of disease had a more severe pelvic disease
      compared to those with scar endometriosis. Complete surgical excision was
      curative but left a large defect requiring polypropylene mesh repair in two
      patients. CONCLUSION: Cutaneous endometriosis should be suspected in any female
      presenting with cyclic or non-cyclic pain emanating from a mass in the vicinity
      of a previous surgical scar, the umbilicus or in the inguinal region. Surgical
      excision of the cutaneous endometriotic implants can be easily performed and is
      curative.

PMID- 18830546
TI  - Cleft deformities in Singapore: a population-based series 1993-2002.
AB  - INTRODUCTION: Cleft deformities, though non-lethal, receive much attention from
      parents and doctors alike because of their obvious physical disfigurement, social
      stigma and associated feeding and vocal articulation problems. There is also an
      association with chromosomal defects for certain cleft deformities. The aim of
      this study is to examine the incidence, demographic data and epidemiological
      trend of this condition over a ten-year period, and to compare our data with
      other local studies, as well as to examine the chromosomal defects associated
      with this condition. METHODS: Data of cleft deformity cases born during the
      period 1993-2002 was retrieved from the National Birth Defects Registry and
      analysed. RESULTS: There were a total of 859 cases of cleft deformities in the
      ten-year period 1993-2002, giving an overall incidence of 1.87 per 1,000 live
      births, with an increasing trend noted. Incidence was highest among the Chinese
      and lowest among the Indians. There were more males with cleft deformities
      compared with females. The risk of aneuploidy rose by about ten-fold in syndromic
      cleft cases, compared to non-syndromic cleft cases. There were two cases of
      Trisomy 21 in the non-syndromic cleft lip and palate group, giving an incidence
      of 1:133. CONCLUSION: The race-specific and gender-specific differences in cleft
      incidence suggest genetic and environmental factors which warrant further
      studies. The increased risk of aneuploidy among syndromic clefts, as well as the
      finding of Trisomy 21 in non-syndromic cleft lip and palate cases suggest a need
      for karyotyping in these two groups of antenatally-diagnosed cleft deformities.

PMID- 18830547
TI  - Congenital diaphragmatic hernia in a developing country.
AB  - INTRODUCTION: Outcome of neonates with congenital diaphragmatic hernia (CDH)
      varies widely and the data from developing countries is scanty. We aimed to study
      the management and outcome of CDH. We also aimed to ascertain prenatal and
      postnatal factors affecting the outcome. METHODS: A retrospective review of
      neonates with CDH admitted to a teaching hospital was conducted. Demographical
      data, prenatal and postnatal factors, birth details, management and outcomes were
      studied. Survival was the primary outcome. RESULTS: 16 live-born neonates with
      diaphragmatic hernia were admitted during the study period. All neonates had
      hernia on the left side. Mean (standard deviation) gestational age and birth
      weight were 38.6 (1.5) weeks and 2,616.6 (457) g, respectively. Polyhydramnios
      was associated in one patient, and additional anomalies in five patients (31.3
      percent). Overall survival was 56.3 percent. The CDH was detected prenatally in
      four and postnatally in 12 patients. 12 neonates underwent surgery and nine
      survived. Prenatally-detected cases had significantly reduced survival to
      surgery, overall survival and lower Apgar scores at one minute (p-value is less
      than 0.04). Median age at surgery was 48 hours. Average duration of mechanical
      ventilation among survivors was 91.5 hours. Neonatal intensive care unit stay
      ranged from five to 27 (median nine) days. Six of seven deaths occurred within 72
      hours of life. Non-survivors had significantly low Apgar scores and were
      symptomatic within 12 hours of life (p-value is less than 0.03). CONCLUSION:
      Greater than 50 percent survival of neonates with CDH was observed in a centre
      with conventional ventilation. Poor outcome is likely in neonates who present
      within 12 hours of life.

PMID- 18830548
TI  - Circadian rhythm in cardiac arrest: the Singapore experience.
AB  - INTRODUCTION: There appears to be a circadian rhythm in the timing of
      cardiovascular and neurovascular events. The majority of studies have been
      conducted in western populations. This is the first study to look at the peaks
      and distribution of out-of-hospital cardiac arrest (OHCA) patients in Singapore.
      METHODS: The Cardiac Arrest and Resuscitation Epidemiology Studies I and II were
      prospective observation studies on OHCA in Singapore from October 1, 2001 to
      October 14, 2004. This study analysed data for patients older than 16 years. All
      data was collected and recorded as per the Utstein style template. Analysis was
      done for each of the quadrants of the 24-hour clock: 0001-0600, 0601-1200, 1201
      1800 and 1801-2400 hours. RESULTS: Of the 2,428 cases, 2,167 OHCA patients
      qualified for the final analysis. Their mean ages were in the 60s for all the
      four quadrants, with a male predominance. The two peaks noted were at 0800 and
      1900 hours for cardiac causes of death (n = 1,591), and at 0900 and 2000 hours
      for non-cardiac causes of death (n = 576). At all times of the day, the majority
      of OHCA occurred in residences and the bystander cardiopulmonary resuscitation
      rate ranged from 14.6 to 24.3 percent in the different quadrants of the day.
      CONCLUSION: OHCA has a bimodal distribution in our local cohort of patients. The
      information obtained will be utilised for fine-tuning emergency medical services
      strategies, as we strive to improve our current survival rates for OHCA.

PMID- 18830549
TI  - Seasonal variation in plasma levels of lithium in the Indian population: is there
      a need to modify the dose?
AB  - INTRODUCTION: Lithium still remains an important choice in the therapy of manic
      depressive psychosis (MDP), and though there are reports of seasonal variation in
      lithium levels from a few countries, such studies have not been conducted in
      India. Variability in the lithium level can lead to lack of efficacy or toxicity,
      making seasonal variation clinically relevant. METHODS: A retrospective case
      sheet audit was performed for 101 MDP patients for recording plasma lithium
      level, oral lithium dose, age and gender for one year. The overall average oral
      lithium dose and level were recorded; the monthly average to which it most
      closely matched was noted as the control month, and values of other months were
      compared with this control month by Friedman's test followed by Dunn's test.
      RESULTS: The mean age of patients was 38.22 (standard deviation 12.07) years, and
      72 out of 101 patients were male. The mean lithium dose in November (938.61 +/-
      243.40 mg/day), which was the closest to the overall mean dose (938.24 +/- 241.78
      mg/day) was taken as the control month, which when compared with other monthly
      values, did not show any significant difference. The June (0.54 +/- 0.23 meq/L),
      July (0.55 +/- 0.24 meq/L) and August (0.55 +/- 0.24 meq/L) mean plasma lithium
      values were significantly high when compared to the October value (0.45 +/- 0.22
      meq/L) as control. High-low variability between the plasma lithium values of
      different months was found to be 25 percent. CONCLUSION: The present study showed
      a significant high variability of lithium levels in different months of the year,
      therefore frequent plasma level monitoring and oral lithium dose adjustment to
      prevent situations of toxicity and lack of efficacy in MDP.

PMID- 18830550
TI  - Magnetic resonance imaging of variants of the knee.
AB  - Magnetic resonance imaging has become the imaging modality of choice for
      evaluation of internal derangements of the knee. Anatomical variants are often an
      incidental finding on these examinations. Knowledge and recognition of variants
      is important, not only to avoid misdiagnosis but also to avoid additional imaging
      and over-treatment. This pictorial essay provides an overview of variants
      encountered during a review of 1,873 magnetic resonance imaging examinations of
      the knee. Emphasis is laid on these variants that are clinically important.

PMID- 18830552
TI  - Perceived helpfulness of websites for mental health information: a national
      survey of young Australians.
AB  - BACKGROUND: Despite the high risk of developing a mental disorder during
      adolescence, many young people fail to receive appropriate treatment from mental
      health professionals. Recent studies have found certain mental health information
      websites have improved mental health literacy and reduced symptoms of depression.
      However, studies exploring young people's perceptions of such resources still
      remain scarce. The current paper compared young people's preference for a website
      with self-help books and two face-to-face services-counselling and mental health
      services. The factors associated with believing in the perceived helpfulness of
      each intervention were also explored. METHOD: A national telephone survey was
      carried out with 3,746 people aged 12-25 years and 2005 co-resident parents.
      Perceived helpfulness of each intervention was assessed in relation to four
      vignettes (depression, social phobia, psychosis and depression with alcohol
      misuse). RESULTS: Approximately 71% of respondents rated websites and books as
      likely to be helpful, which was less than for counselling, but more than for
      mental health services. Predictors of rating a website as likely to be helpful
      were older age (18-25 years), belief in seeking help, less social distance from
      peers like the one in the vignette, and being presented with the vignettes
      depicting either social phobia or depression with alcohol misuse. Predictors of
      rating a book as helpful included belief in seeking help, awareness of the
      national depression initiative beyondblue, less social distance, being presented
      with the social phobia vignette, and the belief that the person in the vignette
      is 'weak not sick'. CONCLUSION: Most young people are open to the idea of
      accessing mental health information online, especially for disorders that are
      often perceived as behavioural problems. These young people also believe in help
      seeking in general and are more willing to associate with peers who have mental
      health problems.

PMID- 18830553
TI  - Randomized trial of preemptive local analgesia in vaginal surgery.
AB  - Preemptive analgesia in vaginal surgery has had conflicting efficacy reported in
      the existing literature. This study was designed to clarify the usefulness of
      preemptive local analgesia (PLA) in patients undergoing vaginal hysterectomy. A
      prospective, randomized, double-blinded trial of PLA in 90 women undergoing
      vaginal hysterectomy was conducted. PLA consisted of 20 ml of 0.5% bupivacaine
      with 1:200,000 epinephrine injected in a paracervical-type fashion. Total
      narcotic use and pain (using a visual analog scale (VAS)) was recorded at 30 min,
      3, 12, and 24 h postoperatively. The mean total dose of narcotic was
      significantly less in the PLA group versus the placebo group (P = 0.009) at every
      time point postoperatively. Additionally, the mean pain VAS 30 min and 3 h
      postoperatively was 43% (P = 0.003) and 33% (P = 0.02) lower, respectively, in
      the PLA group. PLA with bupivacaine prior to vaginal hysterectomy is associated
      with significantly lower pain scores and a reduction in narcotic use
      postoperatively.

PMID- 18830554
TI  - Poor glycemic control is associated with low BMD detected in premenopausal women
      with type 1 diabetes.
AB  - SUMMARY: The etiology of bone fragility in individuals with type 1 diabetes is
      unknown. This study demonstrated that bone turnover favors resorption and that
      poor glycemic control is associated with low bone mineral density (BMD) and low
      bone turnover, in premenopausal women with type 1 diabetes. The results could
      inform future interventions. INTRODUCTION: Low BMD and fracture may be
      complications of type 1 diabetes. We sought to determine the roles of bone
      turnover and glycemic control in the etiology of low BMD. METHODS: Premenopausal
      women from the Wisconsin Diabetes Registry Study and matched controls were
      compared (n = 75 pairs). Heel and forearm BMD were measured, and hip and spine
      BMD were measured in a subset. Markers of bone formation (osteocalcin) and
      resorption (NTx), and glycemic control (HbA1c) were determined. RESULTS: Age
      ranged from 18 to 50 years with a mean of 28, and 97% were Non-Hispanic white.
      Among women with diabetes, mean disease duration was 16 years and current HbA1c
      was 8%. Compared to controls, women with diabetes had a high prevalence of
      previous fracture (37% vs. 24%) and low BMD for age (heel or forearm: 49% vs.
      31%), low heel and forearm BMD, and low osteocalcin levels. Levels of NTx were
      similar, suggesting uncoupled turnover favoring resorption. Poor glycemic control
      was associated with low BMD at all bone sites except the spine, and with low
      osteocalcin and NTx levels. CONCLUSIONS: Optimal glycemic control may prevent low
      BMD and altered bone turnover in type 1 diabetes, and decrease fracture risk.

PMID- 18830555
TI  - DXA-based hip structural analysis of once-weekly bisphosphonate-treated
      postmenopausal women with low bone mass.
AB  - SUMMARY: DXA-based hip structural analysis from 947 individuals completing two
      large osteoporosis clinical trials was pooled and analyzed. Treatment with once
      weekly (OW) ALN or OW RIS resulted in significant improvements from baseline in
      geometric parameters at all three HSA ROIs. Improvements were generally greater
      with OW ALN than OW RIS. INTRODUCTION: BMD can be altered by changes in
      distribution and quantity of bone and changes in mineralization. These effects
      cannot be distinguished with conventional measurements of BMD. Currently, tissue
      composition is evaluated only by invasive means. Structural geometry of the
      proximal femur, however, can be measured in vivo by several methods, including
      dual energy X-ray absorptiometry (DXA) using specialized hip structure analysis
      (HSA) software. METHODS: DXA-based HSA was obtained and analyzed in a subset of
      947 subjects participating in the Fosamax Actonel Comparison Trials. Data were
      pooled to evaluate treatment effects on the structural geometry of the proximal
      femur by once-weekly alendronate (ALN) 70 mg and risedronate (RIS) 35 mg in
      postmenopausal women with low bone mass. RESULTS: Both ALN and RIS treatment over
      2 years resulted in improvements in HSA-derived geometry at all three HSA regions
      of interest (ROI). The largest treatment effects were seen at the
      intertrochanteric ROI. Consistently greater treatment effects were seen with ALN
      compared with RIS at all three HSA-ROIs. CONCLUSIONS: HSA offers insight into the
      potential mechanisms of fracture risk reduction from pharmacologic intervention.
      In the current study, treatment with once-weekly bisphosphonates resulted in
      significant improvements in hip geometric parameters.

PMID- 18830556
TI  - Aortic root abscess without involvement of the aortic valve in a child caused by
      Panton-Valentine leukocidin-positive staphylococci.
AB  - Aortic root abscess without any involvement of the aortic valve is extremely
      rare. This report describes an 11-year-old girl with subperiosteal abscess due to
      a virulent organism called Panton-Valentine leukocidin-secreting staphylococci.
      Although her initial transthoracic echocardiogram did not show any cardiac
      abnormality, she subsequently experienced an aortic root abscess communicating
      with the left ventricle. The aortic valve was unaffected, and no other cardiac
      abnormality was detected at any stage. The girl made a complete recovery after
      surgical intervention for her aortic root abscess, which was increasing in size
      despite antibiotic therapy. Patients with such illnesses require close monitoring
      with repeated expert echocardiography and timely intervention.

PMID- 18830557
TI  - Aortic root aneurysm after balloon valvoplasty: evaluation with CT angiography.
AB  - A 15-year-old was admitted in 2001 for aortic valve balloon dilatation. He was
      readmitted in 2005 complaining of fatigue. Echocardiography showed severe aortic
      regurgitation. Computed tomography revealed aneurysm of aorta near the orifice of
      the left main coronary artery. He underwent uneventful Ross procedure combined
      with aneurysmectomy.

PMID- 18830558
TI  - Low human paraoxonase predicts cardiovascular events in Japanese patients with
      type 2 diabetes.
AB  - Human serum paraoxonase (PON1) is associated with HDL and inhibits oxidative
      modification of LDL. PON1 enzymatic activity has been shown to decrease in
      diabetic patients; however, the effect of PON1 status on long-term outcome has
      not been reported. In this study, we examined the association between baseline
      PON1 status and the development of cardiovascular disease (CVD) during 10 years
      of follow-up in 88 type 2 diabetic patients whose enzymatic activities,
      concentrations, and genetic polymorphisms of PON1 had been determined. A total of
      20 CVD events were recorded during the follow-up period. Using Kaplan-Meier
      survival curves, we found a significantly increased incidence of CVD in patients
      with a lower concentration or paraoxonase activity of PON1 than each median value
      (log-rank 7.460; P < 0.01, and log-rank 4.187; P < 0.05, respectively). By Cox
      regression analysis, both concentration and paraoxonase activity were
      significantly associated with the development of CVD, even after correction for
      gender, age, and preexisting CVD (P < 0.05). Low concentration and enzymatic
      activity of PON1 may be an independent predictor of cardiovascular events in
      diabetic patients.

PMID- 18830559
TI  - A single test procedure to diagnose gestational diabetes mellitus.
AB  - Universal screening for gestational diabetes mellitus (GDM), detects more cases
      and improves maternal and offspring prognosis. Of all the screening tests, World
      Health Organization (WHO) procedure is simple and cost effective; the only
      disadvantage is that the pregnant woman has to come in the fasting state to
      undergo oral glucose tolerance test (OGTT). Hence, we undertook a study to
      elucidate a test that is casual and reliable to diagnose GDM. A total of 800
      pregnant women underwent 75-g glucose challenge test (GCT) irrespective of the
      time of the last meal and their 2-h plasma glucose (PG) was estimated. They also
      underwent a 2-h 75-g OGTT recommended by WHO after 72 h. There was no
      statistically significant difference in the glycemic profile between GCT and WHO
      OGTT in the diagnosis of GDM. In conclusion, GCT performed irrespective of the
      last meal timing is a patient-friendly approach and causes least disturbance in
      the pregnant woman's routine activities.

PMID- 18830560
TI  - Acute effect of infection by adipogenic human adenovirus Ad36.
AB  - Human adenovirus Ad36 is causally and correlatively associated in animals and
      humans, respectively, with increased adiposity and altered metabolic profile. We
      inoculated rats with Ad36 or UV-inactivated Ad36, or mock-infected them. Four
      days later, Ad36-infected rats showed 23% greater epididymal fat pad weight and
      viral mRNA; the viral DNA could also be detected in tissues viz. the liver,
      brain, and adipose tissue. Intranasal or intra-peritoneal routes of viral
      inoculation showed similar tissue affinity. The serum cytokine response was
      markedly down-regulated. Ad36 acutely suppresses the systemic immune response and
      spreads widely. This information will help to determine Ad36 tissue tropism and
      its metabolic consequences.

PMID- 18830561
TI  - Shikonin inhibits IgE-mediated histamine release by human basophils and Syk
      kinase activity.
AB  - OBJECTIVE: Shikonin, a component of the herbal medicine "Shikon", is known to
      suppress inflammatory reactions, but its molecular targets are not identified.
      This study examines the effect of shikonin on human basophil degranulation
      response and aims to identify its targets. MATERIALS: Human basophils in isolated
      leukocytes from healthy volunteers' peripheral blood; recombinant human Syk and
      Lyn tyrosine kinases. METHODS: Histamine release from basophils stimulated with
      anti-IgE antibody was analyzed fluorimetrically. Syk and Lyn kinase activities
      were tested in Vitro with recombinant proteins and analyzed by off-chip mobility
      shift assay. RESULTS: Shikonin dose-dependently inhibited the histamine release
      from basophils induced by anti-IgE antibody (IC50 = 2.6 +/- 1.0 microM; mean +/-
      SEM). A search for the target(s) of shikonin in the signal cascade of IgE
      mediated activation showed that it strongly inhibits Syk (IC50 = 7.8 microM, in
      the recombinant kinase assay), which plays a pivotal role in the degranulation
      response. A less significant inhibition was found for Lyn, which phosphorylates
      FcepsilonRI-betagamma subunits and also Syk. CONCLUSIONS: These results indicate
      that the inhibition of Syk-dependent phosphorylation events might underlie the
      blocked histamine release from human basophils, thus contributing to the anti
      inflammatory effects of shikonin.

PMID- 18830562
TI  - LPS-induced endotoxic shock does not cause early brain edema formation - an MRI
      study in rats.
AB  - OBJECTIVE AND DESIGN: Early microcirculatory failure is assumed as a key factor
      in the development of a septic encephalopathy. However, brain edema is also a
      common finding in sepsis syndromes possibly interfering with the vasoregulative
      mechanisms of the brain. We assessed the occurrence of brain edema in a rat model
      of endotoxic shock. MATERIAL AND SUBJECTS: Eleven mechanically ventilated male CD
      rats. TREATMENT: Intravenous application of 5 mg/kg LPS (n = 8) or vehicle (n =
      3). METHODS: Apparent diffusion coefficient (ADC) and T2-relaxation time (T2RT)
      were quantified on cerebral MRI at baseline and repeatedly for up to 3.5 h after
      LPS-injection. Change in blood pressure was compensated with norepinephrine.
      Brain water content was quantified using the wet/dry method. RESULTS: All LPS
      treated rats developed endotoxic shock. No significant difference in T2RT or ADC
      was detectable before and after LPS-injection (T2RT: baseline 60.33 +/- 1.21;
      after 3.5 h 60.15 +/- 0.59; ADC: baseline 6.86 +/- 0.51; after 3.5 h 6.75 +/-
      0.33). Post-mortem analysis did not indicate a difference in brain water content
      between septic and non-septic animals. CONCLUSIONS: Reports of early
      microcirculatory failure seem not to be related to the occurrence of early (< or
      =3.5 h) brain edema.

PMID- 18830563
TI  - The anti-inflammatory and anti-cancer properties of epigallocatechin-3-gallate
      are mediated by folate cycle disruption, adenosine release and NF-kappaB
      suppression.
AB  - OBJECTIVE: To understand the mechanism by which (-)-epigallocatechin-3-gallate
      (EGCG), the major polyphenol of green tea, exerts its anti-inflammatory action.
      METHODS: To check our hypothesis that the anti-inflammatory properties of EGCG
      could be related to its antifolate action and whether adenosine and its receptors
      are involved in EGCG action, we investigated the EGCG-induced suppression of NF
      kappaB in Caco-2 cell monolayer, which acted as a model of the human intestinal
      epithelium. RESULTS: We demonstrate that the anti-inflammatory properties of EGCG
      are associated with its antifolate activity. By using a natural stable folate we
      were able to reverse the EGCG suppression of TNF-alpha-induced NF-kappaB
      activation, the phosphorylation and degradation of IkappaBalpha and the
      phosphorylation of Akt in this human colon carcinoma cell line. These
      suppressions were mediated by the release of adenosine following disruption of
      the folate cycle by EGCG. By binding to its specific receptors, adenosine can
      modulate the Akt and NF-kappaB pathway. Moreover, EGCG produces a significant
      increase in a specific adenosine receptor, which could explain the suppression of
      the constitutive activation of NF-kappaB in colon cancer cells. CONCLUSIONS: The
      data suggest that by modulating NF-kappaB activation, EGCG might not only combat
      inflammation, but also cancer.

PMID- 18830564
TI  - Fundus autofluorescence changes in two cases of Sjogren-Larsson syndrome.
AB  - Sjogren-Larsson syndrome (SLS) is a rare autosomal recessive neurocutaneous
      disorder characterized by the triad of intellectual disability, spastic diplegia
      or tetraplegia, and congenital ichthyosis with associated ocular features, which
      include macular glistening dots. Herein, two cases of SLS are presented and their
      fundus autofluorescence changes, which have not been reported so far, are
      described.

PMID- 18830565
TI  - Solution structure of the Grb2 SH2 domain complexed with a high-affinity
      inhibitor.
AB  - The solution structure of the growth factor receptor-bound protein 2 (Grb2) SH2
      domain complexed with a high-affinity inhibitor containing a non-phosphorus
      phosphate mimetic within a macrocyclic platform was determined by nuclear
      magnetic resonance (NMR) spectroscopy. Unambiguous assignments of the bound
      inhibitor and intermolecular NOEs between the Grb2 SH2 domain and the inhibitor
      was accomplished using perdeuterated Grb2 SH2 protein. The well-defined solution
      structure of the complex was obtained and compared to those by X-ray
      crystallography. Since the crystal structure of the Grb2 SH2 domain formed a
      domain-swapped dimer and several inhibitors were bound to a hinge region, there
      were appreciable differences between the solution and crystal structures. Based
      on the binding interactions between the inhibitor and the Grb2 SH2 domain in
      solution, we proposed a design of second-generation inhibitors that could be
      expected to have higher affinity.

PMID- 18830566
TI  - Early use of omeprazole benefits patients with acute myocardial infarction.
AB  - BACKGROUND: Bleeding complications are not uncommon in patients with acute
      myocardial infarction (AMI) during treatments. How to prevent the occurrence of
      upper gastrointestinal bleeding in AMI patients has become one of the most
      intractable problems. And there are conflicting data on the efficacy and
      complication rate of omeprazole treatment. We conducted an intervention study to
      determine whether using omeprazole could benefit AMI patients. METHODS: A total
      of 237 patients with AMI were divided into two groups at random: omeprazole group
      including 114 patients and control group including 123 patients. Omeprazole 40 mg
      by intravenous drip was given to the patients in omeprazole group when they were
      admitted to the hospitals. From the second day they were given omeprazole 20 mg
      per day by oral administration for 7 days. In contrast, no gastric acid inhibitor
      was given to the patients in control group. The incidence of upper
      gastrointestinal bleeding, the recanalization rate and overall mortality in both
      groups were observed. RESULTS: The incidence of upper gastrointestinal bleeding
      in omeprazole group was 5.3% (6/114) which was much lower than 14.6% (18/123) in
      control group (P = 0.017), but the recanalization rate had no significant
      difference between the two groups (P = 0.681). The overall mortality in
      omeprazole group was lower than that of control group (3.5% vs. 10.6%, P =
      0.035). CONCLUSIONS: Our findings suggest that early use of omeprazole in AMI
      patients could decrease the incidence of upper gastrointestinal bleeding and the
      overall mortality, without influencing the recanalization rate. Early use of
      omeprazole might benefit AMI patients.

PMID- 18830567
TI  - Differing expression of genes involved in non-transferrin iron transport across
      plasma membrane in various cell types under iron deficiency and excess.
AB  - We studied the effect of iron deficiency, i.e., 24-h preincubation in iron-free
      medium, and the effect of high level of non-transferrin iron, i.e., the
      preincubation in ferric citrate medium containing 500 microM ferric citrate, on
      the expression of DMT1, Dcytb, ferroportin, hephaestin, and ceruloplasmin in
      various functional types of human cells. The expression of these proteins
      potentially involved in non-transferrin iron transport across cell membranes was
      tested on mRNA level by quantitative real-time PCR as well as on protein level by
      western blot analysis in Caco-2 (colorectal carcinoma), K562 (erythroleukemia),
      and HEP-G2 (hepatocellular carcinoma) cells. We found that changes in non
      transferrin iron availability, i.e., iron deficiency and high level of non
      transferrin iron, affect the expression of tested proteins in a cell type
      specific manner. We also demonstrated that changes in the expression on mRNA
      level do not often correlate with relevant changes on protein level.

PMID- 18830568
TI  - Activated human neutrophils rapidly release the chemotactically active D2D3 form
      of the urokinase-type plasminogen activator receptor (uPAR/CD87).
AB  - The urokinase-type plasminogen activator receptor (uPAR/CD87) exists both in cell
      bound and soluble forms. Neutrophils contain extensive intracellular pools of
      uPAR that are translocated to the plasma membrane upon activation. In the present
      study, we investigated the ability of human neutrophils to shed uPAR from cell
      surface following activation and addressed the possible involvement of the
      released receptor in the inflammatory response. We first observed that the
      spontaneous release of suPAR by resting neutrophils was strongly and rapidly
      (within minutes) enhanced by calcium ionophore ionomycin and to a lesser extent
      when cells were primed with TNF-alpha and then stimulated with fMLP or IL-8. We
      demonstrated that suPAR is produced by resting and activated neutrophils
      predominantly as a truncated form devoid of N-terminal D1 domain (D2D3 form) that
      lacks GPI anchor. Migration of formyl peptide receptor-like 1 (FPRL1)-transfected
      human embryonic kidney (HEK) 293 cells toward the supernatants harvested from
      activated neutrophils was significantly diminished when D2D3 form of suPAR was
      immunodepleted from the supernatants. We conclude that activated neutrophils
      release the chemotactically active D2D3 form of suPAR that acts as a ligand of
      FPRL1. Interestingly, we present evidence that GPI-specific phospholipase D (GPI
      PLD) that has previously been shown to shed uPAR in cancer cells is not involved
      in suPAR release from human neutrophils. We suggest that production of the
      chemotactically active D2D3 form of suPAR by activated human neutrophils in vivo
      could contribute to the recruitment of monocytes and other formyl peptide
      receptors-expressing cells to the sites of acute inflammation where neutrophil
      accumulation and activation occur.

PMID- 18830569
TI  - Role of immunoexpression of nitric oxide synthases by Hodgkin and Reed-Sternberg
      cells on apoptosis deregulation and on clinical outcome of classical Hodgkin
      lymphoma.
AB  - Hodgkin and Reed-Sternberg (H-RS) cells of classical Hodgkin lymphoma (cHL)
      present an impaired expression of immunoglobulin genes, but escape apoptotic
      death. We investigated whether nitric oxide synthases (NOS) are expressed by H-RS
      cells, studied their association with EBV status and the expression of apoptotic
      proteins, and investigated their relationship to the clinical outcome of 171
      patients. NOS1 and NOS2 were expressed in a large number of cases, whereas NOS3
      expression was not detected. Positive associations were found between NOS1 and
      p53, bax and NOS2, bcl-2 and NOS2, bax and p53, and between bax and fasL. Inverse
      correlations were established between EBV and NOS2 and between EBV and bcl-2. A
      shorter overall survival (OS) was associated with strong expression of NOS2. In
      conclusion, NOS are expressed by H-RS cells of cHL.

PMID- 18830570
TI  - Liver-specific ZP domain-containing protein (LZP) as a new partner of Tamm
      Horsfall protein harbors on renal tubules.
AB  - Liver-specific ZP domain-containing protein (LZP) was recently identified as a
      secreted protein that is specifically expressed in liver. However, the
      physiological effects of LZP are largely unknown. In this study, we found that
      LZP was detectable in mouse kidneys, testes, ovaries and heart, in addition to
      liver. LZP was localized in the spermatid cells of testes, corpus luteum cells of
      ovaries, and cardiac muscle cells of heart. But the protein mainly anchored on
      the apical membrane of the thick ascending limb of the loop of Henle (TAL) cell
      in mouse kidney. In rat kidney LZP and Tamm-Horsfall protein (THP) were co
      localized in TAL. The in vivo interaction between LZP and THP was confirmed in
      kidney and urine by co-immunoprecipitation assay, and the in vitro interaction
      was detected by GST pull-down assay, implying that the interaction could be
      independent on N-linked glycosylated modification of LZP. Surprisingly, LZPs with
      intramolecular disulfide bridges could self-interact, and then self-aggregate
      into spheres of varying sizes, but not polymerize into filaments. The finding
      that LZP might act as a new partner of THP would provide novel insights into
      renal functions related to THP and LZP, such as the urothelial permeability
      barrier and the host defense against the adhesion of pathogens.

PMID- 18830571
TI  - Ameliorative effect of combination of benfotiamine and fenofibrate in diabetes
      induced vascular endothelial dysfunction and nephropathy in the rat.
AB  - The study has been designed to investigate the effect of benfotiamine and
      fenofibrate in diabetes-induced experimental vascular endothelial dysfunction
      (VED) and nephropathy. The single administration of streptozotocin (STZ) (50
      mg/kg, i.p.) produced diabetes, which was noted to develop VED and nephropathy in
      8 weeks. The diabetes produced VED by attenuating acetylcholine-induced
      endothelium dependent relaxation, impairing the integrity of vascular
      endothelium, decreasing serum nitrite/nitrate concentration and increasing serum
      TBARS and aortic superoxide anion generation. Further, diabetes altered the lipid
      profile by increasing the serum cholesterol, triglycerides and decreasing the
      high density lipoprotein. The nephropathy was noted to be developed in the
      diabetic rat that was assessed in terms of increase in serum creatinine, blood
      urea, proteinuria, and glomerular damage. The benfotiamine (70 mg/kg, p.o.) and
      fenofibrate (32 mg/kg, p.o.) or lisinopril (1 mg/kg, p.o., a standard agent)
      treatments were started in diabetic rats after 1 week of STZ administration and
      continued for 7 weeks. The treatment with benfotiamine and fenofibrate either
      alone or in combination attenuated diabetes-induced VED and nephropathy. In
      addition, the combination of benfotiamine and fenofibrate was noted to be more
      effective in attenuating the diabetes-induced VED and nephropathy when compared
      to treatment with either drug alone or lisinopril. Treatment with fenofibrate
      normalizes the altered lipid profile in diabetic rats, whereas benfotiamine
      treatment has no effect on lipid alteration in diabetic rats. It may be concluded
      that diabetes-induced oxidative stress, lipids alteration, and consequent
      development of VED may be responsible for the induction of nephropathy in
      diabetic rats. Concurrent administration of benfotiamine and fenofibrate may
      provide synergistic benefits in preventing the development of diabetes-induced
      nephropathy by reducing the oxidative stress and lipid alteration, preventing the
      VED and subsequently improving the renal function.

PMID- 18830572
TI  - Retroviral immunology: lessons from a mouse model.
AB  - Friend virus (FV) is a murine retrovirus that causes acute disease leading to
      lethal erythroleukemia in most strains of mice. Strains of mice that mount strong
      and rapid immune responses can recover from acute infection, but nevertheless
      develop life-long chronic infections. The study of this infection has revealed
      the types of immune responses required for both recovery from the acute phase and
      the control of the chronic phase of infection. This knowledge has led to vaccines
      and therapeutics to prevent and treat infections and associated disease states.
      The FV model has provided insights into immunological mechanisms found to be
      relevant to human infections with retroviruses such as HIV-1 and HTLV-1.

PMID- 18830574
TI  - [Posttraumatic disorders in the cranio-mandibular system and the cervical spine].

PMID- 18830573
TI  - [Neuralgia of the genitofemoral nerve after hernioplasty. Therapy by peripheral
      nerve stimulation].
AB  - The peripheral nerve stimulation (PNS) is an established therapy in the
      management of neuropathic pain. Here, we describe a case of successful epifascial
      stimulation in the proximity of the genitofemoral nerve, which was injured during
      an endoscopic hernioplasty. During the following months the patient developed an
      intense neuropathy of this nerve, which we now treated by permanent PNS with an 8
      polar electrode. During the 1 year follow-up the patient described a pain
      reduction of nearly 70%. There were no adverse events until now. In conclusion,
      PNS is a promising procedure in the treatment of neuralgia after hernioplasty.

PMID- 18830575
TI  - [Not electroconvulsive therapy, but its opponents are in the firing line].

PMID- 18830576
TI  - [Novel neuroimaging perspectives in the diagnosis of dementia].
AB  - Neuroimaging is an essential part of the etiological diagnosis of dementia. In
      this review, techniques that enhance the information extracted from routine
      magnetic resonance imaging (MRI) are presented. In addition, novel techniques of
      MR acquisition and analyses are reported that may become part of routine
      diagnostics in the future. These include automated analysis of structural MRI,
      proton MR spectroscopy, diffusion tensor imaging, perfusion MRI, and functional
      MRI. From nuclear medicine, the key techniques of fluorodeoxyglucose positron
      emission tomography (FDG-PET) and dopamine transporter single photon emission
      computed tomography (SPECT) for early and differential diagnosis of Alzheimer's
      dementia and Lewy body dementia and the innovation of amyloid PET are presented.

PMID- 18830577
TI  - Association mapping reveals gene action and interactions in the determination of
      flowering time in barley.
AB  - The interaction between members of a gene network has an important impact on the
      variation of quantitative traits, and can influence the outcome of
      phenotype/genotype association studies. Three genes (Ppd-H1, HvCO1, HvFT1) known
      to play an essential role in the regulation of flowering time under long days in
      barley were subjected to an analysis of nucleotide diversity in a collection of
      220 spring barley accessions. The coding region of Ppd-H1 was highly diverse,
      while both HvCO1 and HvFT1 showed a rather limited level of diversity. Within all
      three genes, the extent of linkage disequilibrium was variable, but on average
      only moderate. Ppd-H1 is strongly associated with flowering time across four
      environments, showing a difference of five to ten days between the most extreme
      haplotypes. The association between flowering time and the variation at HvFT1 and
      HvCO1 was strongly dependent on the haplotype present at Ppd-H1. The interaction
      between HvCO1 and Ppd-H1 was statistically significant, but this association
      disappeared when the analysis was corrected for the geographical origin of the
      accessions. No association existed between flowering time and allelic variation
      at HvFT1. In contrast to Ppd-H1, functional variation at both HvCO1 and HvFT1 is
      limited in cultivated barley.

PMID- 18830578
TI  - Arterial pressure changes during the Valsalva maneuver to predict fluid
      responsiveness in spontaneously breathing patients.
AB  - OBJECTIVE: To evaluate whether arterial pressure response during a Valsalva
      maneuver could predict fluid responsiveness in spontaneously breathing patients.
      DESIGN AND SETTING: Prospective clinical study in a 17-bed multidisciplinary
      intensive care unit. PATIENTS: Thirty patients without mechanical ventilation and
      equipped with a radial arterial catheter for whom the decision to give fluids was
      taken due to suspected hypovolemia. INTERVENTION: A 10-s Valsalva maneuver was
      performed before and after volume expansion (VE). Patients were classified as
      responders if stroke volume index (SVi) increased >/=15% after VE. MEASUREMENTS
      AND RESULTS: Pulse pressure changes during the Valsalva maneuver (VPP) were
      calculated as the difference between maximal pulse pressure during phase 1 and
      minimal pulse pressure during phase 2 of the Valsalva maneuver divided by the
      mean of the two values and expressed as a percentage. Valsalva changes in
      systolic pressure (VSP) were calculated in similar way. SVi changes induced by VE
      was correlated with baseline values of VPP and VSP (r (2) = 0.71 and r (2) =
      0.60; P < 0.0001, respectively), and with VE-induced changes in VPP and VSP (r
      (2) = 0.56 and r (2) = 0.44; P < 0.0001 and P < 0.001, respectively). A VPP value
      of 52% and VSP of 30% predicted fluid responsiveness with a sensitivity of 91%
      and 73% and a specificity of 95 and 90%, respectively. CONCLUSIONS: Arterial
      response during the Valsalva maneuver is a feasible tool for predicting fluid
      responsiveness in patients without mechanical ventilatory support.

PMID- 18830579
TI  - Valsalva, Valsalva, may you give me a clue, who needs fluids in my ICU?

PMID- 18830580
TI  - Evaluation of lesion in a spontaneous osteonecrosis of the knee using 18F
      fluoride positron emission tomography.
AB  - Positron-emission tomography (PET) imaging has several advantages over
      conventional scintigraphy, including a high spatial resolution and the ability to
      quantify disease progression. Recently, (18)F-fluoride PET has been applied to
      the evaluation of malignant tumors and musculoskeletal disorders. In our current
      study, spontaneous osteonecrosis of the knee (SONK) was visualized using this
      technique. We determined whether PET images can reveal SONK lesions, whether
      there were significant differences in the maximum standardized uptake value
      (SUVmax) among each of the SONK stages, and finally if there was any correlation
      between the maximum SUVmax value and size of the SONK lesion measured both by
      radiography and MRI. Fourteen knees from 13 patients diagnosed with SONK were
      imaged using a PET scanner. In all cases, PET showed an accumulation of 18F
      fluoride in the medial condyle. The SUVmax ranged from 8.6 to 23.7 with an
      average of 15.1 +/- 3.7 and was measured at different disease stages with an
      average of 12.4 +/- 5.9 in Stage 2 (n = 5), 16.3 +/- 1.4 in Stage 3 (n = 4), and
      16.8 +/- 4.3 (n = 5) in Stage 4 lesions. There were no significant differences in
      these measurements between the SONK stages. However, a significant positive
      correlation between the SUVmax and lesion size, including the surface area of the
      lesion (r2 = 0.692, P = 0.0002) and the condyle width ratio (r2 = 0.365, P =
      0.022), was found. The approximate volumes of the lesions measured by MRI had an
      average of 4.8 +/- 3.1 cm3, and also showed a significant correlation with the
      SUVmax (r2 = 0.853, P < 0.0001). Hence, our present results indicate that a high
      SUV is indicative of a large SONK lesion.

PMID- 18830581
TI  - A new tourniquet system that determines pressures in synchrony with systolic
      blood pressure in knee surgery.
AB  - This study reports the results of the clinical use of a new tourniquet system for
      surgery related to knee joint that can determine tourniquet pressure in synchrony
      with systolic blood pressure (SBP). We prospectively applied additional pressure
      of 100 mmHg based on the SBP recorded just before infiltration of tourniquet in
      163 consecutive procedures, which consisted of 73 TKA related surgeries, 42
      arthroscopic related surgeries, 20 ACL reconstructed surgeries, 15 ORIF, and 13
      other surgeries. After the infiltration, the tourniquet pressure was
      automatically synchronized with the SBP. The interval of the measurement of blood
      pressure was every 2.5 min. The average durations of the operation and tourniquet
      use were 56 (range 6-134) and 56 (range 8-125) min, respectively. The average
      initial systolic tourniquet pressure was 207 mmHg (range 178-302). The average
      maximum changes during surgery were 37 mmHg (range 2-102) systolic and 23 mmHg
      (range 5-67) diastolic. The average maximum systolic pressure changes during 2.5
      min interval were 20 mmHg (range 5-97). All cases kept a good operative field
      without measurable bleeding and there were no postoperative complications. Sixty
      eight (42%) cases had a lower intra-operative SBP than the initial value. Since a
      tourniquet should be applied at the lowest pressure, and for the shortest amount
      of time possible, the new system appears to be practical and reasonable for
      maintaining a bloodless surgical field, as compared to conventional tourniquets,
      which maintain the initial pressure between 300 and 350 mmHg.

PMID- 18830582
TI  - Characterization of 4-nonylphenol-degrading bacterial consortium obtained from a
      textile wastewater pretreatment plant.
AB  - 4-Nonylphenol (4-NP) isomers are toxic and recalcitrant compounds often
      resulting, together with short-chain ethoxylated nonylphenol (NPnEO, where n is
      the number of ethylene oxide units), from NPnEO biodegradation in conventional
      activated sludge plants. In this work, a microbial consortium, defined as
      Consortium A, capable of removing 100 mg/L of 4-NP with no accumulation of
      metabolites with aromatic moiety was isolated from textile wastewaters after
      enrichment with 4-NP. The consortium showed remarkable degradation activities
      toward several short-chain NPnEO congeners. Culture-dependent techniques were
      used to isolate from the consortium twenty-six strains assigned to seven
      different amplified ribosomal DNA restriction analysis groups. Two- and three
      member cocultures were prepared with the strains showing highest 4-NP-degrading
      capabilities, but neither the single strains nor the cocultures were as efficient
      in 4-NP degradation as Consortium A. FISH was used to characterize the microbial
      composition of Consortium A: it evidenced a strong occurrence of Proteobacteria
      and, in particular, of Gammaproteobacteria along with a relevant stability of the
      culture. Therefore, the isolated consortium has the potential of being used in
      the development of a biotechnological process for the tertiary treatment of
      effluents of activated sludge plants fed with NPnEO-contaminated wastewaters.

PMID- 18830583
TI  - Aluminium and lead toxicity revisited: mechanisms explaining the particular
      sensitivity of the brain to oxidative damage.

PMID- 18830584
TI  - Colombistatin: a disintegrin isolated from the venom of the South American snake
      (Bothrops colombiensis) that effectively inhibits platelet aggregation and SK-Mel
      28 cell adhesion.
AB  - Snake venoms are complex mixtures of proteins, which affect the vital biologic
      systems of prey, as well as humans. Envenomation leads to immobilization by
      paralysis, cardiac, and circulatory failure. These same venom proteins that cause
      havoc in the physiologic system could be used as therapeutic agents. Disintegrins
      and disintegrin-like proteins are molecules found in the venom of four snake
      families (Atractaspididae, Elapidae, Viperidae, and Colubridae). The disintegrins
      are non-enzymatic proteins that inhibit cell-cell interactions, cell-matrix
      interactions, and signal transduction. These proteins may have potential in the
      treatment of strokes, heart attacks, cancers, osteoporosis, and diabetes. The
      present study describes the isolation and characterization of a disintegrin
      (colombistatin) found in the venom of the Venezuelan snake mapanare (Bothrops
      colombiensis). Colombistatin was purified by a two-step high-performance liquid
      chromatography procedure, which included reverse phase C18 and size exclusion
      protein Pak 60. Colombistatin inhibited ADP-induced platelet aggregation, human
      urinary (T24) and skin melanoma (SK-Mel-28) cancer cell adhesion to fibronectin,
      and cell migration. Colombistatin contained 72 amino acids with a mass of 7.778
      kDa as determined by mass spectrometry. Colombistatin could be used as a
      therapeutic tool in the treatment of melanoma cancers and also thrombotic
      diseases.

PMID- 18830585
TI  - Compensatory manual motor responses while object wielding during combined linear
      visual and physical roll tilt stimulation.
AB  - Dynamic signals from multiple sensory channels must be integrated by the central
      nervous system to create a unified perception of self-motion and spatial
      orientation. Using immersive virtual environments, we altered the relative
      contribution of visual and inertial inputs and evaluated the effects on
      perceptuomotor outputs. Subjects seated in a tilting chair were exposed to a
      combined 0.25 Hz sinusoidal roll-tilt (+/-7.5 degrees) about the naso-occipital
      axis while viewing one of four visual conditions. One visual condition was in
      darkness, and the other three depicted 2 m of sinusoidal horizontal or vertical
      linear motion either synchronous or asynchronous with the roll-tilt. Subjects
      performed a perceptuomotor task of aligning a handheld object to gravitational
      vertical (GV) with the entire arm being free to move in six degrees of freedom.
      Subjects were tested with two objects, a joystick and glass of water, in counter
      balanced order. Specific visual effects were as follows: (1) the phase leads of
      object tilt relative to chair/subject roll-tilt were affected by visual
      condition, (2) horizontal translation of the object was entrained with visual
      velocity, rather than with visual acceleration or maximum roll-tilt, and (3) when
      vertical visual motion was viewed during chair/subject roll-tilt, vertical object
      translation increased. Although the head-fixed scene meant visual vertical cues
      were always aligned with the subject's median sagittal plane, object tilt showed
      sensitivity to inertial roll-tilt (Gain > 0.5) which was not significantly
      different from the dark condition. Two object effects were found: (1) tilt
      deviation from GV was greater when wielding a joystick compared to a full glass
      of water, and (2) the phase of horizontal visual motion relative to subject roll
      tilt affected the joystick amplitude of horizontal translation but not the glass
      of water. In conclusion, an attentional shift driven by postural assumptions can
      account for the two object effects, however, the visual effects suggest that a
      process for deriving the net gravitoinertial force from visual and inertial cues
      is involved. Inertial signals dominated the perception of verticality, but visual
      linear translation affected the spatiotemporal dynamics of the manual motor
      responses during object wielding.

PMID- 18830586
TI  - Human brain activity time-locked to rapid eye movements during REM sleep.
AB  - To identify the neural substrate of rapid eye movements (REMs) during REM sleep
      in humans, we conducted simultaneous functional magnetic resonance imaging (fMRI)
      and polysomnographic recording during REM sleep. Event-related fMRI analysis time
      locked to the occurrence of REMs revealed that the pontine tegmentum,
      ventroposterior thalamus, primary visual cortex, putamen and limbic areas (the
      anterior cingulate, parahippocampal gyrus and amygdala) were activated in
      association with REMs. A control experiment during which subjects made self-paced
      saccades in total darkness showed no activation in the visual cortex. The REM
      related activation of the primary visual cortex without visual input from the
      retina provides neural evidence for the existence of human ponto-geniculo
      occipital waves (PGO waves) and a link between REMs and dreaming. Furthermore,
      the time-course analysis of blood oxygenation level-dependent responses indicated
      that the activation of the pontine tegmentum, ventroposterior thalamus and
      primary visual cortex started before the occurrence of REMs. On the other hand,
      the activation of the putamen and limbic areas accompanied REMs. The activation
      of the parahippocampal gyrus and amygdala simultaneously with REMs suggests that
      REMs and/or their generating mechanism are not merely an epiphenomenon of PGO
      waves, but may be linked to the triggering activation of these areas.

PMID- 18830587
TI  - Tapping with intentional drift.
AB  - When tapping a desired frequency, subjects tend to drift away from this target
      frequency. This compromises the estimate of the correlation between inter-tap
      intervals (ITIs) as predicted by the two-level model of Wing and Kristofferson
      which consists of an internal timer ('clock') and motor delays. Whereas previous
      studies on the timing of rhythmic tapping attempted to eliminate drift, we
      compared the production of three constant frequencies (1.5, 2.0, and 2.5 Hz) to
      the production of tapping sequences with a linearly decreasing inter-tap interval
      (ITI) (corresponding to an increase in tapping frequency from 1.5 to 2.5 Hz). For
      all conditions a synchronization-continuation paradigm was used. Tapping forces
      and electromyograms of the index-finger flexor and extensor were recorded and
      ITIs were derived yielding interval variability and model parameters, i.e., clock
      and motor variances. Electromyographic recordings served to study the influence
      of tapping frequency on the peripheral part of the tap event. The condition with
      an increasing frequency was more difficult to perform, as evidenced by an
      increase in deviation from the intended ITIs. In general, tapping frequency
      affected force level, inter-tap variability, model parameters, and muscle co
      activation. Parameters for the condition with a decreasing ITI were comparable to
      those found in the constant frequency conditions. That is, although tapping with
      an intentional drift is different from constant tapping and more difficult to
      perform, the timing properties of both forms of tapping are remarkably similar
      and described well by the Wing and Kristofferson model.

PMID- 18830588
TI  - Symptoms of hyperactivity and inattention can mediate deficits of postural
      stability in developmental dyslexia.
AB  - Developmental dyslexia is a reading disorder associated with impaired postural
      control. However, such deficits are also found in attention deficit hyperactivity
      disorder (ADHD), which is present in a substantial subset of dyslexia diagnoses.
      Very few studies of balance in dyslexia have assessed ADHD symptoms, thereby
      motivating the hypothesis that such measures can account for the group
      differences observed. In this study, we assessed adults with dyslexia and
      similarly aged controls on a battery of cognitive, literacy and attention
      measures, alongside tasks of postural stability. Displacements of centre of mass
      to perturbations of posture were measured in four experimental conditions using
      digital optical motion capture. The largest group differences were obtained in
      conditions where cues to the support surface were reduced. Between-group
      differences in postural sway and in sway variability were largely accounted for
      by co-varying hyperactivity and inattention ratings, however. These results
      therefore suggest that postural instability in dyslexia is more strongly
      associated with symptoms of ADHD than to those specific to reading impairment.

PMID- 18830589
TI  - Eye hand coordination in children with cerebral palsy.
AB  - Reaching to grasp an object of interest requires complex sensorimotor
      coordination involving eye, head, hand and trunk. While numerous studies have
      demonstrated deficits in each of these systems individually, little is known
      about how children with cerebral palsy (CP) coordinate multiple motor systems for
      functional tasks. Here we used kinematics, remote eye tracking and a trunk
      support device to examine the functional coupling of the eye, head and hand and
      the extent to which it was constrained by trunk postural control in 10 children
      with CP (6-16 years). Eye movements in children with CP were similar to typically
      developing (TD) peers, while hand movements were significantly slower. Postural
      support influenced initiation of hand movements in the youngest children (TD &
      CP) and execution of hand movements in children with CP differentially depending
      on diagnosis. Across all diagnostic categories, the most robust distinction
      between TD children and children with CP was in their ability to isolate eye,
      head and hand movements. Results of this study suggest that deficits in motor
      coordination for accurate reaching in children with CP may reflect coupled eye,
      head, and hand movements. We have previously suggested that coupled activation of
      effectors may be the default output for the CNS during early development.

PMID- 18830590
TI  - Inter-limb transfer of learned ankle movements.
AB  - Inter-limb learning transfer (ILT) between the upper-limbs has been well
      documented, but no corresponding study of the lower limbs has been done. We
      investigated ILT in the lower limbs of subjects who learned to move a cursor
      toward targets within 800 ms using ankle movements: plantar/dorsi-flexion and
      inversion/eversion. Twenty-two healthy right-dominant subjects were divided into
      two groups: half performed the tasks first using the right foot (group RL), and
      the other half performed it first with the left foot (group LR). Targets appeared
      on a computer screen at head-height while subjects were seated with one foot on a
      goniometric ankle platform. Subjects were required to move the cursor toward one
      of three randomly appearing targets under two conditions: (1) neutral or no
      visual motor rotation, and (2) with a 30 degrees visuo-motor rotation.
      Performance was quantified by computing the z-score for direction and position
      errors for each subject and ILT was assessed by comparing group performances for
      each foot. Results demonstrated that group LR but not group RL experienced
      significant ILT of directional as well as positional information in both tasks in
      a manner reflective of the distinctly different functional roles played by the
      upper and lower limbs.

PMID- 18830591
TI  - Properties and axonal trajectories of posterior semicircular canal nerve
      activated vestibulospinal neurons.
AB  - We studied the axonal projections of vestibulospinal neurons activated from the
      posterior semicircular canal. The axonal projection level, axonal pathway, and
      location of the vestibulospinal neurons originating from the PC were investigated
      in seven decerebrated cats. Selective electrical stimulation was applied to the
      PC nerve, and extracellular recordings in the vestibular nuclei were performed.
      The properties of the PC nerve-activated vestibulospinal neurons were then
      studied. To estimate the neural pathway in the spinal cord, floating electrodes
      were placed at the ipsilateral (i) and contralateral (c) lateral vestibulospinal
      tract (LVST) and medial vestibulospinal tract (MVST) at the C1/C2 junction. To
      elucidate the projection level, floating electrodes were placed at i-LVST and
      MVST at the C3, T1, and L3 segments in the spinal cord. Collision block test
      between orthodromic inputs from the PC nerve and antidromic inputs from the
      spinal cord verified the existence of the vestibulospinal neurons in the
      vestibular nuclei. Most (44/47) of the PC nerve-activated vestibulospinal neurons
      responded to orthodromic stimulation to the PC nerve with a short (<1.4 ms)
      latency, indicating that they were second-order vestibulospinal neurons. The rest
      (3/47) responded with a longer (>/=1.4 ms) latency, indicating the existence of
      polysynaptic connections. In 36/47 PC nerve-activated vestibulospinal neurons,
      the axonal pathway was histologically verified to lie in the spinal cord. The
      axons of 17/36 vestibulospinal neurons projected to the i-LVST, whereas 14
      neurons projected to the MVST, and 5 to the c-LVST. The spinal segment levels of
      projection of these neurons elucidated that the axons of most (15/17) of
      vestibulospinal neurons passing through the i-LVST reached the L3 segment level;
      none (0/14) of the neurons passing through the MVST extended to the L3 segment
      level; most (13/14) of them did not descend lower than the C3 segment level. In
      relation to the latency and the pathway, 33/36 PC nerve-activated vestibulospinal
      neurons were second-order neurons, whereas the remaining three were polysynaptic
      neurons. Of these, 33 second-order vestibulospinal neurons, 16 passed through the
      i-LVST, while 13 and 4 descended through the MVST and c-LVST, respectively. The
      remaining three were polysynaptic neurons. Histological analysis showed that most
      of the PC nerve-activated vestibulospinal neurons were located within a specific
      area in the medial part of the lateral vestibular nucleus and the rostral part of
      the descending vestibular nucleus. In conclusion, it was suggested that PC nerve
      activated vestibulospinal neurons that were located within a focal area of the
      vestibular nuclei have strong connections with the lower segments of the spinal
      cord and are related to postural stability that is maintained by the short
      latency vestibulospinal reflex.

PMID- 18830592
TI  - Pressure jump relaxation investigations of lipid membranes using FTIR
      spectroscopy.
AB  - The relaxation kinetics of aqueous lipid dispersions after a pressure jump (p
      jump) were investigated using time-resolved FTIR spectroscopy. The methylene
      stretching vibrational band and the carbonyl band were analyzed to detect changes
      in conformational order of the hydrocarbon chains and to follow the degree of
      hydration of the head group, respectively. The kinetics of the transition was
      found to consist of multiple processes with relaxation constants from seconds
      down to milliseconds. Faster processes are also present, but could not be
      resolved by our instrument. This is the first investigation showing directly the
      time resolved change in chain order in lipid bilayers induced by a p-jump. The
      results obtained with this IR detection method support previous results that the
      change in chain order after a perturbation is a multi-step process with the
      initial molecular events occurring with time constants shorter than milliseconds.

PMID- 18830593
TI  - Three-dimensional computed tomography analysis of non-osteoarthritic adult
      acetabular dysplasia.
AB  - OBJECTIVE: Little data exists on the original morphology of acetabular dysplasia
      obtained from patients without radiographic advanced osteoarthritic changes. The
      aim of this study was to investigate the distribution and degree of acetabular
      dysplasia in a large number of patients showing no advanced degenerative changes
      using three-dimensional computed tomography (3DCT). MATERIALS AND METHODS: Eighty
      four dysplastic hips in 55 consecutive patients were studied. All 84 hips were in
      pre- or early osteoarthritis without radiographic evidence of joint space
      narrowing, formation of osteophytes or cysts, or deformity of femoral heads. The
      mean age at the time of CT scan was 35 years (range 15-64 years). 3D images were
      reconstructed and analyzed using recent computer imaging software (INTAGE Realia
      and Volume Player). Deficiency types and degrees of acetabular dysplasia were
      precisely evaluated using these computer software. RESULTS: The average Harris
      hip score at CT scans was 82 points. Twenty-two hips (26%) were classified as
      anterior deficiency, 17 hips (20%) as posterior deficiency, and 45 hips (54%) as
      lateral deficiency. No significant difference was found in the Harris hip score
      among these groups. The analysis of various measurements indicated wide
      variations. There was a significant correlation between the Harris hip score and
      the acetabular coverage (p < 0.001). CONCLUSION: Our results indicated wide
      variety of deficiency type and degree of acetabular dysplasia. Hips with greater
      acetabular coverage tended to have a higher Harris hip score.

PMID- 18830594
TI  - Zebularine suppresses the apoptotic potential of 5-fluorouracil via cAMP/PKA/CREB
      pathway against human oral squamous cell carcinoma cells.
AB  - PURPOSE: During tumorigenesis, tumor suppressor and tumor-related genes are
      commonly silenced by aberrant DNA methylation in their promoter regions, which is
      one of the important determinants of susceptibility to 5-fluorouracil (5-FU) in
      oral squamous cell carcinoma (OSCC) cells. Here, we examine the chemotherapeutic
      efficacy of epigenetic agents on 5-FU cytotoxicity. METHOD: We investigated the
      effect of a DNA methyltransferase (DNMT) inhibitor, zebularine (Zeb), on the
      chemosensitivity of 5-FU and cisplatin (CDDP) by MTT and TUNEL methods, and
      compared the molecular mechanism of action with those of a GSK3beta inhibitor,
      LiCl, and an Hsp90 inhibitor, 17-AAG. RESULTS: A significant apoptotic effect by
      a combination of Zeb or 17-AAG was found in CDDP treatment; however, considerable
      suppression of 5-FU-induced apoptosis was observed after incubation with Zeb, 17
      AAG, or LiCl. Zeb's suppressive effects were associated with activation of the
      cAMP/PKA/CREB pathway, differing from mechanisms of 17-AAG and LiCl. Suppression
      of 5-FU-induced apoptosis by Zeb was not associated with increased Bcl-2 and Bcl
      xL expressions dependent on transcription factor CREB, and with the expression
      level of thymidylate synthase. CONCLUSIONS: In the present study, we identified a
      more detailed mechanism of action by which Zeb suppresses 5-FU-induced apoptosis.
      These results indicate that combination therapies have to be carefully
      investigated due to potential harmful effects in the clinical application of DNMT
      inhibitors.

PMID- 18830595
TI  - A stimulus-dependent connectivity analysis of neuronal networks.
AB  - We present an analysis of interactions among neurons in stimulus-driven networks
      that is designed to control for effects from unmeasured neurons. This work builds
      on previous connectivity analyses that assumed connectivity strength to be
      constant with respect to the stimulus. Since unmeasured neuron activity can
      modulate with the stimulus, the effective strength of common input connections
      from such hidden neurons can also modulate with the stimulus. By explicitly
      accounting for the resulting stimulus-dependence of effective interactions among
      measured neurons, we are able to remove ambiguity in the classification of causal
      interactions that resulted from classification errors in the previous analyses.
      In this way, we can more reliably distinguish causal connections among measured
      neurons from common input connections that arise from hidden network nodes. The
      approach is derived in a general mathematical framework that can be applied to
      other types of networks. We illustrate the effects of stimulus-dependent
      connectivity estimates with simulations of neurons responding to a visual
      stimulus.

PMID- 18830596
TI  - Watson-Crick pairing, the Heisenberg group and Milnor invariants.
AB  - We study the secondary structure of RNA determined by Watson-Crick pairing
      without pseudo-knots using Milnor invariants of links. We focus on the first non
      trivial invariant, which we call the Heisenberg invariant. The Heisenberg
      invariant, which is an integer, can be interpreted in terms of the Heisenberg
      group as well as in terms of lattice paths. We show that the Heisenberg invariant
      gives a lower bound on the number of unpaired bases in an RNA secondary
      structure. We also show that the Heisenberg invariant can predict allosteric
      structures for RNA. Namely, if the Heisenberg invariant is large, then there are
      widely separated local maxima (i.e., allosteric structures) for the number of
      Watson-Crick pairs found.

PMID- 18830597
TI  - Henoch-Schonlein pupura complicated by perforation of the gallbladder.
AB  - Henoch-Schonlein purpura is a systemic vasculitis of small vessels characterized
      by purpura, arthralgias, glomerulonephritis and gastrointestinal involvements
      which can cause intestinal perforation. A 75-year-old man with renal dysfunction
      and palpable purpura (petechiae) of which dermal specimen showed leukocytoclastic
      vasculitis was diagnosed as Henoch-Schonlein purpura. Corticosteroid and
      cyclosporine were effective, but subsequently he developed pneumocystis
      pneumonia. After he improved by treatment with trimethoprim-sulfamethoxazole, he
      presented sudden abdominal pain, caused by perforation of the gallbladder.
      Histological analysis revealed infiltration of inflammatory cells with bleeding
      in the gallbladder wall at the site of perforation. It is suggested that
      inflammatory disruption of capillary walls might lead to the perforation of the
      gallbladder.

PMID- 18830598
TI  - The importance of severity of arthrosis for the reliability of bone mineral
      density measurement in women.
AB  - The objective of this study is to investigate the effect of the severity of
      degenerative changes on measurements of A-P lumbar spines BMD values and to
      determine the reliability of DEXA measurements associated with severity of the
      disease on A-P lumbar spines BMD values using DEXA. The measurements using DEXA
      were taken from L2-L4 spines and femoral neck of total 271 female cases. One
      hundred and ten of them had mild arthrosis (Group 0), and 69 had severe arthrosis
      (Group 1). Ninety-two cases without arthrosis were chosen as control group (Group
      2). The cases with arthrosic changes were grouped according to their degree of
      severity of arthrosis. The groups were compared two by two and Tukey multiple
      comparison test was used for the analysis of the difference of the means of the
      groups. The mean age of cases was 61.79, 61.84, and 60.47, respectively. The
      average height was 157.26, 155.93, and 15.92 cm while the average weight was
      69.21, 70.78, and 71.45 kg, respectively. The mean body mass index (BMI) was
      0.00283, 0.00291, and 0.00293, respectively. L2-L4 A-P spinal BMD values were
      0.9870, 0.9848, and 1.0836 g/cm(2) while the femoral neck BMD values were 0.7964,
      0.8056, and 0.8223 g/cm(2), respectively. There was no statistical significance
      between study and control groups in terms of age, weight, height, BMI, and BMD
      values obtained from femoral neck. However, lumbar region BMD values of the cases
      with severe arthrosis were statistically significantly high when compared with
      other two groups. The femoral neck measurement is the prominent alternative
      method in severe arthrosis while taking measurements from lumbar region is still
      the most appropriate method in cases with mild arthrosis without having giant
      osteophytes.

PMID- 18830599
TI  - [Ophthalmologic publications from Germany].
AB  - BACKGROUND: The German contribution to the worldwide publication activity in
      ophthalmology had not yet been explored properly. METHODS: A quantitative
      bibliometric analysis of ophthalmologic publications for the years 1993-2007 was
      performed using the online database of the Institute for Scientific Information
      (ISI). The analysis used eight selected search words as well as publication
      activities of 45 journals in the ISI category "ophthalmology." RESULTS: The
      analysis according to search words revealed a proportion of 9.9% for
      ophthalmologic publications from Germany and a proportion of 8.9% according to
      journal-specific publication activities. The contribution of publications from
      Germany in English-language journals was 5.9%. Approximately two-thirds of the
      German publications were written in English and one-third in German. Germany
      ranked second behind the United States in absolute publication numbers but was
      behind other Anglo-Saxon and Scandinavian countries when the numbers were
      adjusted for population size. CONCLUSION: German ophthalmologic publications have
      reached an appreciable level in the international literature.

PMID- 18830600
TI  - [Multiple familiar trichoepithelioma (Brooke's syndrome) : A rare autosomal
      dermatosis with possible periocular manifestation].
AB  - Brooke's syndrome is a rare autosomal dominant dermatosis characterized by
      multiple trichoepitheliomas, which preferentially arise in the face. Therapy
      consists of excisional surgery of larger tumors and for multiple lesions, dermal
      abrasion or laser therapy may be considered. Patients with Brooke's syndrome
      should be closely followed-up due to the possible development of malignant skin
      tumours. Here, we present a patient with Brooke's syndrome and report on the
      course of treatment.

PMID- 18830601
TI  - [Vitreal-induced RPE cell traction. Investigation of pathological vitreous
      samples in an in vitro contraction model].
AB  - BACKGROUND: The aim of this study was to quantify the contraction of retinal
      pigment epithelium cells (RPE) induced by bioactive factors in pathological
      vitreous samples. MATERIAL AND METHODS: Using an in vitro contraction assay, the
      contraction-stimulating activity of vitreous samples of different vitreoretinal
      pathologies was evaluated. Transdifferentiated porcine RPE cells were placed on
      hemispherical type I collagen gel. After exposure to pathological vitreous
      samples derived from different entities (physiological (n=6), rhegmatogenous
      retinal detachment (n=11), proliferative vitreoretinopathy (PVR) (=10),
      proliferative diabetic retinopathy (n=6)) the induced gel contraction was
      determined. RESULTS: The specific activity of the unclassified samples was 0.04
      (median, range: 0-0.08). Vitreous samples derived from patients diagnosed as
      having any grade of PVR displayed a specific activity of 0.45 (median, range:
      0.03-1.45). Samples removed from patients with rhegmatogenous retinal detachment
      disclosed a specific activity of 0.13 (median, range: 0.01-0.93). The specific
      activity of vitreous samples removed from patients with diabetic retinopathy had
      a specific activity of 0.17 (median, range: 0.06-0.29). The mean specific and
      total activities of these groups were significantly elevated above the
      unclassified or baseline values (p<0.05). CONCLUSION: Pathological vitreous
      samples of different vitreoretinal pathologies contain sufficient amounts of
      biologically active factors to induce extracellular matrix contraction.

PMID- 18830602
TI  - [The Hermann grid illusion: the classic textbook interpretation is obsolete].
AB  - The Hermann grid is an optical illusion in which the crossings of white grid
      lines appear darker than the grid lines outside the crossings. The illusion
      disappears when one fixates the crossings. The discoverer, Ludimar Hermann (1838
      1914), interpreted the illusion as evidence for lateral connections in the
      retina. In most textbooks on sensory physiology and ophthalmology, the Hermann
      grid illusion serves to illustrate "lateral inhibition." This paper summarises
      new findings that show that the classic explanation is incomplete. In 2004, a
      seemingly subtle modification, a small undulation of the grid lines, was shown to
      demolish the illusion. In 2007, a more convincing explanation appeared: An
      artificial neural network was trained for "lightness constancy"- the ability of
      our visual system to interpret luminance in the interest of object recognition,
      independent of illumination. After having learned lightness constancy, the
      network was subjected to a number of lightness illusions, among them the Hermann
      grid illusion. An analysis of the coupling constants of this neural network
      promises to further our understanding of the Hermann grid illusion.

PMID- 18830603
TI  - [Biometry of the anterior segment using optical coherence tomography : Evaluation
      of different devices and analysis programs].
AB  - BACKGROUND: Digital visualisation of the anterior eye segment is becoming more
      and more important. Two commercially available optical coherence tomographs
      (OCTs) - Visante OCT (Carl-Zeiss Meditec Jena) and Slit Lamp-OCT (SL-OCT.
      Heidelberg Engineering) - were evaluated. Additionally, a manual and a
      semiautomatic analysis mode for the anterior segment biometry were compared using
      the SL-OCT. PATIENTS AND METHODS: Fifty eyes were examined by three
      ophthalmologists with complete eye status in a standardised fashion. Three
      anterior segment scans (horizontal and vertical) were performed using the Visante
      OCT and the SL-OCT. The manual integrated analysis mode of the Visante OCT was
      used. The best centred SL-OCT scan was analysed with a manual
      (EyelabGlobal/4Optics) and a semiautomatic procedure (HEYEX). Central corneal
      thickness (CCT), anterior chamber depth (ACD), pupillary diameter (PD) and
      chamber angle-angle distance (CAAD) were compared. RESULTS: Comparison of Visante
      OCT and SL-OCT: The horizontal CAAD was 11.65+/-0.47 mm for the Visante-OCT and
      12.0+/-0.57 mm for the SL-OCT (p=0,002), vertical scans were comparable in 10
      eyes only. The CCT was 568+/-61 microm with the Visante-OCT and 581+/-48 microm
      with the SL-OCT (n=35, p=0.03) in horizontal scans and 565+/-62 microm with the
      Visante-OCT and 568+/-51 microm with the SL-OCT in vertical scans (n=27, not
      significant). Deviation of the two measurement methods varied between -54.7 and
      80.8 microm in horizontal scans and between -84.9 and 91.1 microm in vertical
      scans from the mean difference of the two methods. Comparison of the analysis
      programs: Horizontal scans: Manual analysis correlated with semiautomatic
      analysis in CCT as 581+/-51 microm vs. 572+/-53 microm (r=0.903), ACD 2.89+/-0.74
      mm vs. 2.08+/-0.72 mm (r=0.98), PD 5.22+/-2.12 mm vs. 5.14+/-1.91 mm (r=0.917)
      and CAAD 11.59+/-1.02 mm vs. 11.79+/-0.6 mm (r=0.47). The manual and a
      semiautomatic analysis modes for CCT and ACD differed significantly (p<0.026).
      Vertical scan: Manual versus semiautomatic analysis modes correlated in CCT as
      578+/-65 microm vs. 573+/-63 microm (r=0.593), ACD with 3.04+/-0.83 mm vs. 3.03+/
      0.75 mm (r=0.92), PD with 5.28+/-1.99 mm vs. 5.45+/-2.00 mm (r=0.899) and CAAD
      with 11.75+/-0.66 mm vs. 11.82+/-0.6 mm (r=0.537). CONCLUSIONS: A near complete
      investigation of the cornea-anterior-chamber-iris segment is provided by the
      horizontal scan compared with the vertical scan. The noncontact OCT method is an
      easily handled tool for visualisation and biometry of the anterior eye segment.
      The investigated OCTs show a limited comparability. A complete analysis was
      possible in all eyes with the EyelabGlobal system in contrast to the HEYEX
      analysis software. Both analysis programs provided comparable measurements of the
      anterior eye segment. The semiautomatic biometrical mode may reduce the analysis
      time in qualitative excellent and well-centred scans to 10%.

PMID- 18830604
TI  - [Severe open globe injury. New treatment concepts].
AB  - In spite of the technical progress in vitreoretinal surgery, the anatomical and
      functional results of severe ocular injuries involving the posterior segment are
      still discouraging. Perforating injuries and ruptures that extend posterior to
      the muscle insertions have the worst outcomes. When the secondary intervention is
      usually performed between days 7 and 14 post trauma, it is not unlikely that a
      severe proliferative vitreoretinopathy has already occurred. With a new concept-
      to act rather than to react to alterations secondary to severe posterior segment
      trauma--the functional results of these injuries may be further improved,
      according to various studies. The internal reconstruction is in part performed
      together with the primary wound closure, or, alternatively, within 100 h after
      the trauma. This idea is currently being further evaluated in a prospective
      multicenter multinational study conducted by the World Eye Injury Register.

PMID- 18830605
TI  - Gustatory synergism in ants mediates a species-specific symbiosis with lycaenid
      butterflies.
AB  - Here we show that larvae of the lycaenid butterfly Niphanda fusca secrete
      droplets containing trehalose and glycine. These droplets attract the larva's
      host ants Camponotus japonicus, which collect and protect the larvae. We
      comparatively investigated gustatory preference for trehalose, glycine or a
      mixture of the two between host (C. japonicus) and non-host (Camponotus
      obscuripes) species of ants in behavioral and electrophysiological experiments.
      Glycine itself induced no taste sensation in either host or non-host ants. The
      mixture of trehalose plus glycine was chosen as much as pure trehalose by non
      host ants. However, the host ants clearly preferred the mixture of trehalose plus
      glycine to trehalose alone. When we used sucrose instead of trehalose, the
      mixture of sucrose plus glycine was chosen as much as sucrose alone, in both
      species. These behavioral data are supported by the electrophysiological
      responsiveness to sugars and/or glycine in the sugar-taste receptor cells of the
      ants. Considering that lycaenid butterflies' secretions have species-specific
      compositions of sugar and amino acid; our results clearly showed that such
      species-specific compositions of larval secretions are precisely tuned to the
      feeding preferences of their host ant species, in which the feeding preferences
      are synergistically enhanced by amino acid.

PMID- 18830606
TI  - Degree of neuromuscular facilitation is correlated with contribution to walking
      in leg muscles of two species of crab.
AB  - Despite decades of work on the neuromuscular physiology of crustacean leg
      muscles, little is known about how physiological differences between these
      muscles relate to their behavioral usage. We studied a sideways walking shore
      crab, Carcinus maenas, and a forward walking spider crab, Libinia emarginata, as
      part of our work to understand the neural control of locomotion. The two species
      differed significantly in facilitation at neuromuscular junctions for every
      muscle studied. Further, these differences are correlated exactly with the
      walking use of the muscles. The forward walking spider crab showed more
      facilitation in muscles which operate joints having larger ranges of motion in
      forward walking. Likewise, greater facilitation was seen in muscles more active
      during sideways walking in the predominantly sideways walking shore crab. These
      differences even occur between muscles innervated by the same motor neuron, and
      become more evident with higher stimulus frequency. The increased presynaptic
      facilitation might allow selective recruitment of fibers innervated by the same
      motor neuron and aid in temporal filtering.

PMID- 18830607
TI  - Effects of antalarmin, a CRF receptor 1 antagonist, on fright reaction and
      endocrine stress response in crucian carp (Carassius carassius).
AB  - The corticotrophin-releasing factor (CRF) receptors show striking homogeneity
      throughout the vertebrate subphylum. In mammals, the CRF(1) receptor (CRFR(1))
      plays an important role in mediating behavioral and endocrine responses to fear
      and stress. The specific roles of this receptor subtype in fear and stress
      reactions in non-mammalian vertebrates are largely unknown. Crucian carp displays
      the olfactory-mediated fright reaction, a stereotypic behavioral response to
      waterborne cues from damaged skin of conspecifics. This reaction shows several
      similarities to basic components of avoidance behavior in mammals. In the present
      study, we applied the non-peptide CRFR(1) antagonist, antalarmin, to crucian carp
      1 h before exposure to conspecific skin extract. This treatment resulted in a
      suppression of the fright reaction. After skin extract exposure, antalarmin
      treatment also lead to lower plasma cortisol values, as compared to vehicle
      treatment. This suppression of the behavioral fright reaction and the stress
      induced rise in plasma cortisol in crucian carp suggests that the functions of
      the CRFR(1) are conserved by evolution.

PMID- 18830608
TI  - Is radical surgery necessary to head and neck inflammatory myofibroblastic tumor
      (IMT) in children?
AB  - PURPOSE: We report a case of head and neck inflammatory myofibroblastic tumor
      (IMT) in an infant. Reviewing the literature, we discuss the etiology, diagnosis,
      treatment, and prognosis of the head and neck IMT in children. MATERIALS AND
      METHODS: A 52-day-old infant was admitted with an enlarging lesion in the right
      head and neck region. Following total excision, the lesion recurred and
      progressed to terminal stage. We performed a review of the literature on head and
      neck IMTs in children up to the age of 18 years and assessed the treatments and
      related prognosis of IMT in the head and neck region. RESULTS AND CONCLUSIONS:
      The children's prognosis of head and neck IMT is diverse with different
      treatments. Combined treatment of surgical and corticosteroid is recommended for
      younger children, especially infants.

PMID- 18830609
TI  - Infantile spasms in the setting of Sturge-Weber syndrome.
AB  - INTRODUCTION: The prevalence and outcome of the most frequent type of epilepsy in
      infancy-infantile spasms (IS)-are well characterized in the setting of most
      neurocutaneous disorders. By contrast, still there is no study describing the
      natural history of IS in the setting of Sturge-Weber syndrome (SWS). MATERIALS
      AND METHODS: Two patients with SWS and IS were identified in our series and five
      in the literature. The aim of study is to evaluate the clinical,
      electroencephalographic (EEG) and imaging features of our cases and to compare
      our cases with those described in the literature. IS in the setting of SWS is an
      uncommon but possible event (2/19 patients seen over 13 years in our
      institutions). RESULTS: We confirmed the correlation between IS and severity of
      SWS cutaneous and neural (extension of leptomeningeal capillary malformation)
      phenotype. IS in SWS seems to be atypical both from a clinical viewpoint (they
      are asymmetric) and from a laboratory viewpoint (EEG is not classically
      hypsarrhythmic).

PMID- 18830611
TI  - Idiopathic pseudomembranous colitis limited to the right colon: a change from
      Clostridium difficile.

PMID- 18830610
TI  - Chemotherapy is linked to severe vitamin D deficiency in patients with colorectal
      cancer.
AB  - BACKGROUND: Preclinical and clinical evidence support an association between
      vitamin D deficiency and an increased risk of colorectal cancer. Normal vitamin D
      status has been linked to favorable health outcomes ranging from decreased risk
      of osteoporosis to improved cancer mortality. We performed a retrospective study
      to assess the impact of metastatic disease and chemotherapy treatment on vitamin
      D status in patients with colorectal cancer residing in Western New York.
      MATERIALS AND METHODS: Patients, 315, with colorectal cancer treated in a single
      institute were assayed for 25-OH vitamin D. The association of age, gender,
      primary disease site and stage, body mass index, and chemotherapy with vitamin D
      status was investigated. RESULTS: Vitamin D deficiency was common among
      participants with a median 25-OH vitamin D level of 21.3 ng/ml (optimal range 32
      100 ng/ml). Primary site of disease and chemotherapy status were associated with
      very low 25-OH vitamin D levels (< or =15 ng/ml) on multivariate analysis.
      Patients receiving chemotherapy and patients with a rectal primary were 3.7 and
      2.6-fold more likely to have severe vitamin D deficiency on multivariate analysis
      than nonchemotherapy patients and colon cancer primary patients, respectively.
      CONCLUSIONS: Chemotherapy is associated with a significant increase in the risk
      of severe vitamin D deficiency. Patients with colorectal cancer, especially those
      receiving chemotherapy, should be considered for aggressive vitamin D replacement
      strategies.

PMID- 18830612
TI  - VEGF gene polymorphisms and susceptibility to colorectal cancer disease in
      Italian population.
AB  - BACKGROUND: The vascular endothelial growth factor (VEGF) is an endothelial cell
      specific mitogen involved in the process of angiogenesis, a crucial phase in
      tumor growth and metastasis. We carried out a case-control study to evaluate
      whether polymorphisms of VEGF gene modulate the risk of developing colorectal
      cancer disease (CCD). MATERIALS AND METHODS: We evaluated VEGF -2578A/C, -460T/C,
      and +405C/G genotypes obtained from a series of 302 CCD patients and 115 controls
      from the Italian population using polymerase chain reaction restriction fragment
      length polymorphism assay. RESULTS: Strong linkage disequilibrium (LD) was
      detected between -2578A/C and -460T/C (D' = 0.97; CI = 0.93-1) and between 
      2578A/C and +405C/G (D' = 0.97; CI = 0.98-1) in the case group. Complete LD was
      detected between -2578A/C and +405C/G and between -460T/C and +405C/G (D' = 1; CI
      = 0.84-1; CI = 0.82-1, respectively) in the control group. A reduced risk for the
      disease was associated with -2578C/A and -2578C/C (odds ratio (OR) = 0.34, CI =
      0.162-0.676 and OR = 0.38, CI = 0.181-0.775, respectively). A direct association
      was found for carriers of the VEGF -460C/C polymorphism (OR = 3.55; CI = 1.659
      8.469). We identified a protective haplotype -2578A, -460T, and +405G (OR = 0.04;
      CI = 0.009-0.19) and two different high-risk haplotypes -2578A, -460C, and +405G
      (OR = 1.90; CI = 1.31-2.27) and -2578C, -460C, and +405C (OR = 9.62; CI = 1.3
      70.87). CONCLUSIONS: The present study suggests that the VEGF gene polymorphisms
      may play a role in the development of colorectal cancer.

PMID- 18830613
TI  - Evaluation of novel histone deacetylase inhibitors as therapeutic agents for
      colorectal adenocarcinomas compared to established regimens with the histoculture
      drug response assay.
AB  - BACKGROUND AND AIMS: This study was to evaluate the efficacy of histone
      deacetylase (HDAC) inhibitors in colorectal cancer together with other
      established regimens. MATERIALS AND METHODS: Chemosensitivities of 114 colorectal
      cancer patients to established regimens (fluorouracil (5-FU with leucovorin (FL),
      capecitabine, FL with irinotecan (FLIRI), and FL with oxaliplatin (FLOX)) as well
      as five hydroxamic acid derivatives (suberoylanilide hydroxamic acid, PXD101, and
      three novel candidates of CG-1, CG-2, and CG-3) were comparatively evaluated
      using the histoculture drug response assay. RESULTS: The chemosensitivity with
      established regimens was between 34.2% and 52.6%, when the cutoff value of the
      inhibition ratio was set at 30%, and between 54.5% and 84.1% with HDAC
      inhibitors. All HDAC inhibitors displayed synergistic effects in combination with
      established regimens of FLOX and FLIRI (P < or = 0.0001-0.002). Advanced T- and N
      category tumors and patients with synchronous adenoma displayed higher
      chemosensitivity to CG-3, CG-2, and CG-1, respectively, on a multivariate
      analysis (P = 0.023, 0.044, and 0.045, respectively). Tumors with mismatch repair
      defects were closely correlated with chemosensitivities to combined regimens of
      PDX101 with FLOX and FLIRI (P = 0.044 and 0.048, respectively). CONCLUSIONS: Our
      findings firstly demonstrated the chemo-responsiveness of colorectal cancers to
      HDAC inhibitors with therapeutic efficacy comparable to the established regimens.
      Additionally, tumor growth and heredity were significantly associated with
      specific regimens, supporting their possible role as chemosensitive predictors.

PMID- 18830614
TI  - Axonal protection by brain-derived neurotrophic factor associated with CREB
      phosphorylation in tumor necrosis factor-alpha-induced optic nerve degeneration.
AB  - Brain-derived neurotrophic factor (BDNF) is a potent survival and developmental
      factor that is regulated by cyclic AMP-response element binding protein (CREB)
      and has a protective effect against retinal ganglion cell (RGC) death. However,
      the effect of BDNF on the optic nerve axonal degeneration remains to be examined.
      In this study, we show that intravitreal injection of tumor necrosis factor (TNF)
      alpha induces transient increases in phosphorylated-CREB (p-CREB) and BDNF
      expression in the optic nerve. Administration of exogenous BDNF further increased
      the p-CREB and endogenous BDNF level and exerted a neuroprotective effect against
      TNF-alpha-induced axonal loss. The increases in BDNF mRNA and protein induced by
      TNF-alpha were inhibited significantly by a CRE decoy oligonucleotide. The
      protective effect of exogenous BDNF on axons was also inhibited by the CRE decoy
      oligonucleotide. These results suggest that the protective effect of exogenous
      BDNF may be associated with increases in CREB phosphorylation and endogenous BDNF
      in the optic nerve.

PMID- 18830615
TI  - Effects of ginkgo biloba extract EGb761 on expression of RAGE and LRP-1 in
      cerebral microvascular endothelial cells under chronic hypoxia and hypoglycemia.
AB  - Alzheimer's disease (AD), characterized by accumulation of amyloid-beta protein
      (Abeta) in brain parenchyma, is closely associated with brain ischemia. Decreased
      clearance of Abeta from brain is the main cause of Abeta accumulation in sporadic
      AD. However, the mechanisms underlying ischemia-mediated AD pathogenesis remain
      unclear. The receptor for advanced end glycation products (RAGE) and low-density
      lipoprotein receptor-related protein-1 (LRP-1) expressed at blood brain barrier
      (BBB) are actively involved in Abeta clearance. RAGE is thought to be a primary
      transporter of Abeta across BBB into the brain from the systemic circulation,
      while LRP-1 mediates the transport of Abeta out of the brain. Ginkgo biloba
      extract EGb761, a traditional Chinese medicine, has been widely used in the
      treatment of AD. To investigate the effects of EGb761 on the expression of RAGE
      and LRP-1 in endothelial cells in response to ischemic injury, we cultured bEnd.3
      cells, an immortalized mouse cerebral microvessel endothelial cell line, under a
      chronic hypoxic and hypoglycemic condition (CHH) to mimic ischemic injury of BBB,
      and then treated with EGb 761. We found that EGb 761 markedly ameliorated the
      damage (evaluated by MTT assay) from CHH. Moreover, we demonstrated that CHH led
      to a significant increase in the expression of RAGE both at the mRNA and protein
      levels at all times (24, 36, and 48 h), conversely; CHH induced a dramatic
      decrease in LRP-1 mRNA and protein expression at both 36 and 48 h. The results
      indicated that CHH has differential effects on the expression of RAGE and LRP-1.
      Furthermore, EGb761 significantly reversed CHH-induced upregulation of RAGE
      expression and downregulation of LRP-1 expression. Our findings suggest that
      EGb761 favor clearance of Abeta via regulating the expression of RAGE and LRP-1
      during brain ischemia. This may provide a new insight into a possible molecular
      mechanism underlying brain ischemia-mediated AD pathogenesis, and potential
      therapeutic application of EGb 761 in treatment of AD.

PMID- 18830616
TI  - Quantitative microscopy and systems biology: seeing the whole picture.
AB  - Understanding cellular function requires studying the spatially resolved dynamics
      of protein networks. From the isolated proteins we can only learn about their
      individual properties, but by investigating their behavior in their natural
      environment, the cell, we obtain information about the overall response
      properties of the network module in which they operate. Fluorescence microscopy
      methods provide currently the only tools to study the dynamics of molecular
      processes in living cells with high temporal and spatial resolution. Combined
      with computational approaches they allow us to obtain insights in the reaction
      diffusion processes that determine biological function on the scale of cells.

PMID- 18830617
TI  - Expression of cGMP signaling elements in the Grueneberg ganglion.
AB  - The Grueneberg ganglion (GG) is a cluster of neurons localized to the vestibule
      of the anterior nasal cavity. Based on axonal projections to the olfactory bulb
      of the brain, as well as expression of olfactory receptors and the olfactory
      marker protein, it is considered a chemosensory subsystem. Recently, it was
      observed that in mice, GG neurons respond to cool ambient temperatures. In
      mammals, coolness-induced responses in highly specialized neuronal cells are
      supposed to rely on the ion channel TRPM8, whereas in thermosensory neurons of
      the nematode worm Caenorhabditis elegans, detection of environmental temperature
      is mainly mediated by cyclic guanosine monophosphate (cGMP) pathways, in which
      cGMP is generated by transmembrane guanylyl cyclases. To unravel the molecular
      mechanisms underlying coolness-induced responses in GG neurons, potential
      expression of TRPM8 in the murine GG was investigated; however, no evidence was
      found that this ion channel is present in the GG. By contrast, a substantial
      number of GG neurons was observed to express the transmembrane guanylyl cyclase
      subtype GC-G. In the nose, GC-G expression appears to be confined to the GG since
      it was not detectable in other nasal compartments. In the GG, coolness-stimulated
      responses are only observed in neurons characterized by the expression of the
      olfactory receptor V2r83. Interestingly, expression of GC-G in the GG was found
      in this V2r83-positive subpopulation but not in other GG neurons. In addition to
      GC-G, V2r83-positive GG cells also co-express the phosphodiesterase PDE2A. Thus,
      in summary, coolness-sensitive V2r83-expressing GG neurons are endowed with a
      cGMP cascade which might underlie thermosensitivity of these cells, similar to
      the cGMP pathway mediating thermosensation in neurons of C. elegans.

PMID- 18830618
TI  - Electrical and mechanical response of finger flexor muscles during voluntary
      isometric contractions in elite rock-climbers.
AB  - To determine the differences between rock-climbers and controls in finger flexor
      (FF) motor units (MUs) features and activation strategy, eleven climbers and ten
      controls volunteered for the study. After maximal voluntary contraction (MVC)
      assessment, five levels of isometric contractions at 20, 40, 60, 80 and 100% MVC
      were performed. During contractions, electromyogram (EMG) and mechanomyogram
      (MMG) were recorded, from which the root mean square (RMS) and mean frequency
      (MF) were calculated. Climbers showed significantly higher MVC. EMG RMS was
      statistically higher in climbers than in controls from 60 to 100% MVC. In
      climbers MMG RMS increased up to 80% MVC, whereas in controls it increased only
      up to 60% MVC. MMG MF was higher in climbers than in controls from 60 to 100% MVC
      (P < 0.05). EMG-MMG combined analysis revealed significant differences in MU
      activation strategy between the two groups. The results are compatible with a
      shift of climbers' muscles toward faster MUs.

PMID- 18830619
TI  - A comparison of the kinematics, kinetics and muscle activity between pneumatic
      and free weight resistance.
AB  - Pneumatic devices provide a resistance comprising minimal mass, possibly
      affording greater movement velocities, compared to free weight, while reducing
      the influence of momentum. Thirty men completed three testing sessions [free
      weight (FW), ballistic (BALL) and pneumatic (P)] each consisting of a one
      repetition maximum (1RM) and six sets (15, 30, 45, 60, 75 and 90% 1RM) of four
      explosive repetitions of a bench press. Dependent variables were expressed as
      mean and as a percentage of the concentric displacement. Significant differences
      (P < 0.05) were evaluated using two way repeated measures ANOVAs with Holm-Sidak
      post hoc comparisons. On average, the mean and peak P velocity were 36.5 and
      28.3% higher than FW, and 22.9 and 19.1% higher than the BALL movements. The FW
      and BALL peak force were both significantly higher than the P (26.3 and 22.7% for
      FW and BALL, respectively). BALL mean power output was significantly higher than
      the FW and P at loads of 15 and 30% 1RM; however, between loads of 60-90% 1RM the
      highest mean power was produced with a P resistance. A 15% 1RM load maximized the
      peak power for each condition and no significant differences were found between
      the P and BALL. For loads of 45-90% 1RM the force, power and muscle activity were
      higher during the last 10-20% of the concentric displacement when subjects
      employed the P resistance. In summary, pneumatic resistance may offer specific
      advantages over loads comprising only mass (FW and BALL), although not without
      its own limitations.

PMID- 18830620
TI  - Complex modulation of L-type Ca(2+) current inactivation by sorcin in isolated
      rabbit cardiomyocytes.
AB  - Modulation of the L-type Ca(2+) channel (LTCC) by sorcin was investigated by
      measuring the L-type Ca(2+) current (I (Ca,L)) in isolated rabbit ventricular
      myocytes using ruptured patch, single electrode voltage clamp in the absence of
      extracellular Na(+). Fifty millimolars EGTA (170 nM Ca(2+)) in the pipette
      solution buffered bulk cytoplasmic [Ca(2+)], but retained rapid Ca(2+)-dependant
      inactivation of I (Ca,L,). Recombinant sorcin (3 microM) in the pipette
      significantly slowed time-dependant inactivation (tau (fast): 8.8 +/- 0.9 vs.
      15.1 +/- 1.7 ms). Sorcin had no significant effect on I (Ca,L,) after inhibition
      of the sarcoplasmic reticulum (SR). Using 10 mM 1,2-bis(o-N,N,N',N'-tetraacetic
      acid (170 nM Ca(2+)), I (Ca,L) inactivation was then determined by a Ca(2+) 
      independent, voltage-dependant process. Under these conditions, 3 microM sorcin
      speeded up inactivation. A similar effect was observed by substitution of Ca(2+)
      with Ba(2+). Down-regulation of endogenous sorcin to 27 +/- 7% using an RNAi
      adenoviral vector slowed inactivation of I (Ca,L) by approximately 42%. The
      effects of sorcin on voltage-dependant inactivation were mimicked by a truncated
      form of the protein containing only the Ca(2+)-binding domain. This data is
      consistent with two independent actions of sorcin on the LTCC: (1) slowing Ca(2+)
      dependant inactivation and (2) stimulating voltage-dependant inactivation. The
      net effect of sorcin on the time-dependent inactivation of I (Ca,L) was a balance
      between these two effects. Under normal conditions, sorcin slows I (Ca,L)
      inactivation because the effects of Ca(2+)-dependant inactivation out-weigh the
      effects on voltage-dependant inactivation.

PMID- 18830621
TI  - Transcriptional profiling of the PDR gene family in rice roots in response to
      plant growth regulators, redox perturbations and weak organic acid stresses.
AB  - The role of plant pleiotropic drug resistance (PDR) type ATP-binding cassette
      (ABC) transporters remains poorly understood. We characterized the expression of
      the rice pleiotropic drug resistance (PDR) gene family in roots, where PDR
      transporters are believed to have major functions. A prototypical oligonucleotide
      array was developed containing 70-mers chosen in the gene-specific 3'
      untranslated regions of the rice PDR genes, other full-molecule rice ABC
      transporter genes and relevant marker genes. Jasmonates, which are involved in
      plant defense and secondary metabolism, proved major inducers of PDR gene
      expression. Over half of the PDR genes were JA-induced in roots of rice; OsPDR9
      to the highest level. Salicylic acid, involved in plant pathogen defense,
      markedly induced the expression of OsPDR20. OsPDR20 was cDNA cloned and
      characterized. Abscisic acid, typically involved in water deficit responses,
      particularly induced OsPDR3 in roots and shoot and OsPDR6 in rice leaves. OsPDR9
      and OsPDR20 were furthermore up-regulated in response to dithiothreitol- or
      glutathione-induced redox perturbations. Exogenous application of the weak
      organic acids lactic acid, malic acid, and citric acid differentially induced the
      expression of OsPDR3, OsPDR8, OsPDR9 and OsPDR20 in rice seedling roots. This
      transcriptional survey represents a guide for the further functional analysis of
      individual PDR transporters in roots of rice.

PMID- 18830622
TI  - Investigating differentiation mechanisms of the constituent cells of sex cord
      stromal tumours of the ovary.
AB  - SOX-9, an essential factor for male sexual development, can be induced by
      prostaglandin D2 in a Sry-independent mechanism. Recent data suggest that the
      hedgehog pathway is involved in the differentiation of normal Sertoli and Leydig
      cells. The purpose of our study was to investigate the mechanisms involved in the
      differentiation of ovarian sex cord-stromal tumour (SCST) cells. Two Sertoli
      Leydig cell tumours and two granulosa cell tumours with a minor Sertoli element
      were studied using immunohistochemistry on paraffin-embedded tissue sections.
      Sertoli cells expressed anti-Mullerian hormone (AMH), SOX-9, prostaglandin D
      synthase (Pgds) and bcl-2 (in four of four cases); sonic hedgehog (Shh) and p53
      (in three of four cases) and androgen receptors (AR; in one of four cases). Ki-67
      index ranged from 10% to 50%. Leydig cells expressed Shh and AR (two of two
      cases), while they showed no expression of p53, bcl-2 and 0% Ki-67 index.
      Granulosa cells expressed AMH, Pgds, Shh, estrogen receptors, progesterone
      receptors, AR and bcl-2 (in two of two cases) and p53 (in one of two cases). Ki
      67 index was 10% and 40%, respectively. Further investigation is required to
      clarify the role of the molecules outlined above in the histogenesis of ovarian
      SCST, as Pgds-mediated SOX-9 upregulation could provide a reasonable explanation
      for the presence of testicular differentiation in ovarian SCST.

PMID- 18830623
TI  - Current practices in performing frozen sections for thyroid and parathyroid
      pathology.
AB  - In this review article, current trends in thyroid and parathyroid frozen sections
      are discussed. In Japan and other countries, the numbers of thyroid frozen
      sections have been dramatically decreasing over the past decade. The decline in
      the number of thyroid frozen sections has been attributed to two major factors:
      highly diagnostic preoperative fine needle aspiration for papillary carcinomas,
      the most frequent type of thyroid cancers, and the acknowledgment in the
      literature of the disadvantageous frozen sections for follicular tumors. Several
      authors have argued that the frozen section of thyroid nodules should be limited
      only to cases that have a preoperative cytology diagnosis as "atypical" or
      "suspicious". In contrast, frozen sections for parathyroid glands have been
      increasing in numbers. This increase is thought to be largely due to the high
      number of parathyroidectomies for secondary hyperplasia in dialysis patients.
      Frozen sections are usually performed to confirm the removal of parathyroid
      tissue for either cyropreservation or auto-transplantation. It is concluded that
      thyroid and parathyroid frozen section examination is restricted to selected
      situations.

PMID- 18830624
TI  - Acute febrile neutrophilic dermatosis (Sweet's syndrome) in childhood and
      adolescence: two new patients and review of the literature on associated
      diseases.
AB  - OBJECTIVES: The objectives of this study were to analyse the literature on
      Sweet's syndrome in childhood focussing on associated diseases and to suggest
      possible screening procedures for this group of patients. Furthermore, two new
      patients with Sweet's syndrome are reported. METHODS: A literature search was
      performed on Pub med using search terms "sweet* syndrome*" and neutrophil*
      dermatos*. Patients were subdivided into the following groups:
      classic/idiopathic, paraneoplastic, and parainflammatory Sweet's syndrome.
      RESULTS: The literature search revealed 64 patients (including our two patients)
      who were diagnosed with Sweet's syndrome in childhood and adolescence; 27 (42%)
      patients were categorized as "classic/idiopathic Sweet's syndrome". In 37
      patients (58%) chronic associated diseases were reported. Out of these, 21 (33%)
      patients were categorized as "parainflammatory Sweet's syndrome" including
      chronic recurrent multifocal osteomyelitis, vasculitis with aortitis, recurrent
      infections due to immunodeficiencies, arthritis, and systemic lupus
      erythematosus. Sixteen (25%) patients were categorized as "paraneoplastic Sweet's
      syndrome" comprising both malignant and premalignant diseases like leukemia,
      aplastic anaemia, and Fanconi anaemia. As all five (8%) patients treated with
      drugs (granulocyte-colony stimulating factor, retinoid acid) suffered from
      malignant, premalignant, or parainflammatory diseases, these patients were
      categorized according to the underlying disease. Two new children with Sweet's
      syndrome and associated diseases are presented here, one of them suffering from
      recurrent infections and trisomy 21, while the other was diagnosed with CNS
      vasculitis 5(1/2) years after the primary diagnosis. CONCLUSIONS: Sweet's
      syndrome should be considered in differential diagnosis of prolonged fever with
      cutaneous involvement. As most cases of pediatric Sweet's syndrome are associated
      with other diseases we suggest careful screening and monitoring of these patients
      especially concerning malignant/premalignant diseases, immunodeficiencies,
      cardiovascular involvement, autoimmune diseases, and drug associations.

PMID- 18830625
TI  - Usefulness of third-line chemotherapy for women with recurrent ovarian, fallopian
      tube, and primary peritoneal cancer who receive platinum/taxane regimens as first
      line therapy.
AB  - BACKGROUND: Limited information is available regarding the usefulness of third
      line chemotherapy for recurrent ovarian, fallopian tube, and primary peritoneal
      cancer treated with platinum-taxane regimens as first-line therapy. PATIENTS AND
      METHODS: We retrospectively reviewed the medical records of women with ovarian,
      fallopian tube, and primary peritoneal cancer who were treated at the National
      Cancer Center Hospital between 1999 and 2005 to investigate the relations of
      clinicopathological factors to important clinical endpoints such as the response
      rate (RR), time to progression (TTP) and overall survival (OS) after third-line
      chemotherapy. RESULTS: A total of 172 patients received first-line
      platinum/taxane regimens during the study period, among whom 111 had disease
      progression after first-line chemotherapy. Eighty-one of these 111 patients
      received second-line chemotherapy, and 73 had disease progression. Fifty-four of
      the 73 patients with disease progression received third-line chemotherapy. The RR
      to third-line chemotherapy was 40.7% (95% CI, 27.6-53.8%). The median TTP was 4.4
      months (range 0-19.5 months), and the median OS was 10.4 months (range 1.5-44.3
      months). Performance status (PS) and primary drug-free interval (DFI) were
      independent predictive factors for the RR to third-line chemotherapy (P = 0.04
      and P = 0.009). PS and primary DFI were also independent predictive factors for
      TTP and OS on multivariate analysis (P = 0.006, P = 0.005 and P = 0.01, P =
      0.004, respectively). CONCLUSIONS: PS and primary DFI are useful predictors of
      the response to third-line chemotherapy in women with recurrent ovarian,
      fallopian tube, and primary peritoneal cancer. In this setting, however, both of
      these variables are subject to several well-established potential biases and
      limitations; further prospective studies are thus needed.

PMID- 18830626
TI  - Increased expressions of cannabinoid receptor-1 and transient receptor potential
      vanilloid-1 in human prostate carcinoma.
AB  - PURPOSE: Recently, functional cannabinoid receptor-1 (CB1) and vanilloid receptor
      1 (TRPV1) have been described in human prostate and prostate cancer-derived cell
      lines where the activation of the receptors resulted in inhibition of cellular
      growth. We, however, lack the description of the expression of these molecules in
      human prostate cancer (PCC) and in benign prostate hyperplasia (BPH). METHODS:
      Therefore, immunohistochemistry, Western blotting, and quantitative "real-time Q
      PCR were performed to define the expressions of CB1 and TRPV1 in healthy and
      diseased prostate tissues. RESULTS: CB1 was identified in epithelial and smooth
      muscle cells types of the human prostate, whereas TRPV1 was exclusively localized
      to the mucosal cells. We also found that the expression of CB1 and TRPV1 (both at
      the protein and mRNA levels) were significantly up-regulated in PCC. However,
      while the increased expression of TRPV1 showed a proper correlation with
      increasing PCC tumor grades, such phenomenon was not observed with CB1. In
      addition, we also measured markedly elevated CB1 levels in BPH tissues whilst the
      expression of TRPV1 was not altered when compared to healthy control prostate.
      CONCLUSIONS: Our findings strongly argue for that (1) the CB1 and TRPV1 molecules
      as well as their ligands may indeed possess a promising future role in the
      treatment of PCC; (2) TRPV1 may also serve as a prognostic factor in PCC; and (3)
      CB1 may act as a potential target molecule in the therapeutic management of BPH.

PMID- 18830627
TI  - Cetuximab enhances the efficacy of bortezomib in squamous cell carcinoma cell
      lines.
AB  - PURPOSE: Proteasome inhibition has been shown to be effective in multiple myeloma
      and solid tumor models. In this in vitro study, we investigated the antitumor
      effect of bortezomib (Velcade) in combination with cetuximab in squamous cell
      carcinoma cell lines (SCC). METHODS: Dose-escalation studies were performed in
      five squamous cell carcinoma cell lines using bortezomib or cetuximab alone or in
      combination. Cell survival and growth inhibition were measured quantitatively
      using an MTT and LDH assay. RESULTS: Bortezomib alone showed a significant
      antiproliferative activity in all SCC cell lines (P < 0.042), and the activity
      was further significantly enhanced by the addition of cetuximab (P < 0.043).
      CONCLUSIONS: Our results indicate that cetuximab increases the cytotoxic activity
      of bortezomib in SCC cell lines. Combination therapy of SCC with bortezomib and
      cetuximab might be less toxic than conventional drug regimens used in the
      treatment of these tumors.

PMID- 18830628
TI  - Identification of prognosis-related proteins in advanced gastric cancer by mass
      spectrometry-based comparative proteomics.
AB  - PURPOSE: The objective of this study was to identify differentially expressed
      proteins of advanced gastric cancer from patients with different prognosis using
      NanoLC-MS/MS (LTQ) (nanoflow liquid chromatography system interfaced with a
      linear ion trap LTQ mass spectrometer). METHODS: Eight gastric cancer patients
      with relatively early TNM stage and survival time >34 months were identified as
      good survival (group G), while the other eight with late stage and survival time
      <15 months as poor survival (group P). The total protein of the tissue samples
      from each group was extracted and pooled together respectively. The resulting two
      protein mixtures were trypsin-digested and analyzed using NanoLC-MS/MS (LTQ).
      Database searches were done against NCBI non-redundant database and SWISS-PROT
      database and the identified proteins were classified through an online Web Gene
      Ontology Annotation Plot tool. Immunohistochemistry was used to verify candidate
      prognosis-related proteins. RESULTS: There were 284 and 213 proteins identified
      for group G and group P respectively. And 117 proteins were detected exclusively
      in group G and 46 proteins exclusively in group P. These protein markers function
      in calcium ion signaling pathway, cellular metabolism, cytoskeleton formation,
      stress reaction, etc. Among those, the down-regulated expression of S100P was
      verified to claim a poor clinical outcome of gastric cancer patients (P =
      0.0375). CONCLUSION: The MS-based proteomics approach is efficient in identifying
      differentially expressed proteins in relation to prognosis of advanced gastric
      cancer patients. These differentially expressed proteins could be potential
      prognosis-related cancer markers and deserve further validation and functional
      study.

PMID- 18830629
TI  - Immunobiological characterization of Graphidium strigosum experimental infection
      in rabbits (Oryctolagus cuniculus).
AB  - An experimental infection of rabbits with a wild isolate of the gastric nematode
      Graphidium strigosum was carried out. Animals (3.5 months age) were infected with
      1,000 L3 administered by bucoesophagic catheter (five rabbits) or kept as
      uninfected control group (five animals). The infection was maintained for 3
      months. Along the experimental period, some parasitological, hematological and
      immunological parameters were determined. Prepatent period of the infection
      ranged from 30 to 38 days and, at necropsy, average adult helminth counts were
      430.75 +/- 126.12. No significant variations were found in packed cell volume,
      leukocyte, and eosinophil counts along the experimental period. Infection
      elicited a clear serum-specific IgG response, estimated by ELISA, during patency.
      Pooled sera from the patent period of the infection recognized some soluble
      antigens, particularly, a 67-kDa protein. Experimentally infected animals did not
      show cross recognition between G. strigosum, Haemonchus contortus, and
      Teladorsagia circumcincta. However, Western blot analysis with hyperimmune sera
      against H. contortus raised in rabbits and lambs showed cross reactivity between
      this helminth species and G. strigosum.

PMID- 18830630
TI  - Bioassay-guided isolation of antiplasmodial anacardic acids derivatives from the
      whole plants of Viola websteri Hemsl.
AB  - The petroleum ether extract of Viola websteri Hemsl. (Violaceae) was investigated
      for its activity against chloroquine-sensitive strains of Plasmodium falciparum
      using the parasite lactate dehydrogenase assay method. The main antiplasmodial
      principles, 6-(8'Z-pentadecenyl)-salicylic acid (1) and 6-(8'Z, 11'Z, 14'Z
      heptadecatrienyl)-salicylic acid (2), have been isolated from V. websteri for the
      first time. This is the first report on the antiplasmodial activity of the
      compounds from V. websteri.

PMID- 18830631
TI  - Differential influence of gp63-like molecules in three distinct Leptomonas
      species on the adhesion to insect cells.
AB  - Parasites belonging to the Leptomonas genus have been used as model organisms for
      studying biochemical, cellular, and genetic processes unique to members of the
      Trypanosomatidae family. In the present study, the cell-associated and
      extracellular peptidases of three Leptomonas species, Leptomonas collosoma,
      Leptomonas samueli, and Leptomonas wallacei, were assayed and characterized by
      gelatin-sodium dodecyl sulfate polyacrylamide gel electrophoresis. All parasites
      released metallopeptidases, whereas no cell-associated proteolytic activity could
      be detected in the cellular extracts from L. collosoma. Western blotting probed
      with a polyclonal antibody raised against gp63 from Leishmania amazonensis
      revealed two major reactive polypeptides of apparent molecular masses of 63 and
      52 kDa, with different intensities in cellular extracts and released proteins
      from the studied trypanosomatids. Flow cytometry and fluorescence microscopy
      analyses showed that the gp63-like molecules have a surface location. This is the
      first report on the presence of gp63-like molecules in L. collosoma, L. samueli,
      and L. wallacei. The pretreatment of L. samueli and L. wallacei with anti-gp63
      antibody significantly diminished their association index to Aedes albopictus
      cell line (C6/36), suggesting a potential involvement of the gp63-like molecules
      in the interaction process of these insect trypanosomatids with the vector.

PMID- 18830632
TI  - Lack of compensatory body growth in a high performance moose Alces alces
      population.
AB  - Considerable work has been done on disentangling important factors determining
      early development in body size, yet our knowledge of the extent to which animals
      living under varying conditions can achieve catch-up growth for a bad start in
      life is limited. Here, we investigated how body mass at the age of 8 months
      influenced adult body mass in a moose Alces alces population living under
      excellent environmental conditions on the island of Vega in northern Norway. We
      also investigated if mother age and birth date effects on calf body mass
      persisted until adulthood. We show that neither males nor females were able to
      show compensatory growth before they reached adulthood, and that part of the
      variation in adult body mass may have been due to variation in mother age and
      date of birth. The pattern observed in males can be related to their growth
      strategy in relation to reproduction, while such results were not expected in
      females where size-dependent start of reproduction is likely to interact with
      body growth. We suggest that the good environmental conditions experienced on
      Vega led to females having small somatic costs of an early start of reproduction
      or that larger females were able to acquire more resources for growth than their
      smaller conspecifics. In both cases, females that postpone their first
      reproduction may not be able to achieve catch-up growth for their lower early
      body mass compared to females that start reproduction at an early age. Our
      results concur with previous studies indicating that compensatory growth is weak
      in moose, increasing the likelihood that variation in life history characters are
      also transferred between generations.

PMID- 18830633
TI  - The water relations of two evergreen tree species in a karst savanna.
AB  - The ecohydrology of karst has not received much attention, despite the
      disproportionally large contribution of karst aquifers to freshwater supplies.
      Karst savannas, like many savannas elsewhere, are encroached by woody plants,
      with possibly negative consequences on aquifer recharge. However, the role of
      savanna tree species in hydrological processes remains unclear, not least because
      the location and water absorption zones of tree roots in the spatially complex
      subsurface strata are unknown. This study examined the water sources and water
      relations of two savanna trees, Quercus fusiformis (Small) and Juniperus ashei
      (Buchholz) in the karst region of the eastern Edwards Plateau, Texas (USA).
      Stable isotope analysis of stem water revealed that both species took up
      evaporatively enriched water during the warm season, suggesting a relatively
      shallow water source in the epikarst, the transition zone between soil and
      bedrock. Q. fusiformis had consistently higher predawn water potentials than J.
      ashei during drought, and thus was probably deeper-rooted and less capable of
      maintaining gas exchange at low water potentials. Although the water potential of
      both species recovered after drought-breaking spring and summer rain events,
      associated shifts in stem water isotope ratios did not indicate significant
      uptake of rainwater from the shallow soil. A hypothesis is developed to explain
      this phenomenon invoking a piston-flow mechanism that pushes water stored in
      macropores into the active root zones of the trees. Epikarst structure varied
      greatly with parent material and topography, and had strong effects on seasonal
      fluctuations in plant water status. The study suggests that tree species of the
      Edwards Plateau do not commonly reduce aquifer recharge by tapping directly into
      perched water tables, but more likely by reducing water storage in the epikarst.
      A more general conclusion is that models of savanna water relations based on
      Walter's two-layer model may not apply unequivocally to karst savannas.

PMID- 18830634
TI  - Evaluation of aboveground and belowground biomass recovery in physically
      disturbed seagrass beds.
AB  - Several studies addressed aboveground biomass recovery in tropical and
      subtropical seagrass systems following physical disturbance. However, there are
      few studies documenting belowground biomass recovery despite the important
      functional and ecological role of roots and rhizomes for seagrass ecosystems. In
      this study, we compared the recovery of biomass (g dry weight m(-2)) as well as
      the biomass recovery rates in ten severely disturbed multi-species seagrass
      meadows, after the sediments were excavated and the seagrasses removed. Three
      sites were located in the tropics (Puerto Rico) and seven in the subtropics
      (Florida Keys), and all were originally dominated by Thalassia testudinum. Total
      aboveground biomass reached reference values at four out of ten sites studied,
      two in the Florida Keys and two in Puerto Rico. Total belowground biomass was
      lower at the disturbed locations compared to the references at all sites, apart
      from two sites in the Florida Keys where the compensatory effect of opportunistic
      species (Syringodium filiforme and Halodule wrightii) was observed. The results
      revealed large variation among sites in aboveground and belowground biomass for
      all species, with higher aboveground recovery than belowground for T. testudinum.
      Recovery rates for T. testudinum were highly variable across sites, but a general
      trend of faster aboveground than belowground recovery was observed. Equal rates
      between aboveground and belowground biomass were found for opportunistic species
      at several sites in the Florida Keys. These results indicate the importance of
      belowground biomass when assessing seagrass recovery and suggest that the
      appropriate metric to assess seagrass recovery should address belowground biomass
      as well as aboveground biomass in order to evaluate the full recovery of
      ecological services and functions performed by seagrasses. We point out regional
      differences in species composition and species shifts following severe
      disturbance events and discuss ecological implications of gap dynamics in multi
      species seagrass meadows.

PMID- 18830635
TI  - A less invasive surgical approach in the lumbar lateral recess stenosis: direct
      approach to the medial wall of the pedicle.
AB  - The lateral recess is one of the main compression sites in lumbar spinal canal
      stenosis. Lumbar nerve root is mainly entrapped by bony tissue in compression
      syndrome. The patient has a long history of back pain in conjunction with
      claudication symptoms. Besides laminotomy and facetectomy techniques, several
      specific surgical approaches to treat the lateral recess stenosis have been
      described. The surgical technique of bilateral lateral recess decompression via
      subarticular fenestrations used in this study is a less invasive technique, which
      enables to decompress the neural structures while preserving as much of the bony
      structures and ligamentum flavum as preferred. In 16 patients, we measured
      lateral recess heights with computerized tomography. The number of involved
      lumbar segments was one in 11 patients and two in 5 patients. The visual analogue
      scale (VAS) results were maintained before, 3 and 12 months after the operation.
      All patients benefited from the operations. Mean VAS scores were 7.0, 5.5, and
      4.0, respectively. There were not any surgery-related complications. Mean follow
      up period is 22.6 months. The surgical technique described and used in this study
      provides easy access to every zone of lateral recess and is safe and effective in
      treating the lumbar lateral recess stenosis syndrome.

PMID- 18830636
TI  - Accuracy and safety of pedicle screw placement in neuromuscular scoliosis with
      free-hand technique.
AB  - It is a retrospective analytic study of 1,009 transpedicular screws (689 thoracic
      and 320 lumbosacral), inserted with free-hand technique in neuromuscular
      scoliosis using postoperative CT scan. The aim of paper was to determine the
      accuracy and safety of transpedicular screw placement with free-hand technique in
      neuromuscular scoliosis and to compare the accuracy at different levels in such
      population. All studies regarding accuracy and safety of pedicle screw in
      scoliosis represent idiopathic scoliosis using various techniques such as free
      hand, navigation, image intensifier, etc., for screw insertion. Anatomies of
      vertebrae and pedicle are distorted in scoliosis, hence accurate and safe
      placement of pedicle screw is prerequisite for surgery. Between 2004 and 2006, 37
      consecutive patients, average age 20 years (9-44 years), of neuromuscular
      scoliosis were operated with posterior pedicle screw fixation using free-hand
      technique. Accuracy of pedicle screws was studied on postoperative CT scan.
      Placement up to 2 mm medial side and 4 mm lateral side was considered within-safe
      zone. Of the 1,009 screws, 273 screws were displaced medially, laterally or on
      the anterior side showing that 73% screws (68% in thoracic and 82.5% in lumbar
      spine) were accurately placed within pedicle. Considering the safe zone, 93.3%
      (942/1009, 92.4% in thoracic and 95.3% in lumbar spine) of the screws were within
      the safe zone. Comparing accuracy according to severity of curve, accuracy was
      75% in group 1 (curve <90 degrees ) and 69% in group 2 (curve >90 degrees) with a
      safety of 94.8 and 91.2%, respectively (P = 0.35). Comparing the accuracy at
      different thoracic levels, it showed 67, 64 and 72% accuracy in upper, middle and
      lower thoracic levels with safety of 96.6, 89.2 and 93.1%, respectively,
      exhibiting no statistical significant difference (P = 0.17). Pedicle screw
      placement in neuromuscular scoliosis with free-hand technique is accurate and
      safe as other conditions.

PMID- 18830637
TI  - Low back pain in childhood and adolescence: a cross-sectional study in Niigata
      City.
AB  - A cross-sectional study targeted a total of 43,630 pupils in Niigata City, Japan
      was performed. The objective was to clarify the present incidence of low back
      pain (LBP) in childhood and adolescence in Japan. It has recently been recognized
      that LBP in childhood and adolescence is also as common a problem as that for
      adults and most of these studies have been conducted in Europe, however, none
      have so far been made in Japan. A questionnaire survey was conducted using 43,630
      pupils, including all elementary school students from the fourth to sixth grade
      (21,893 pupils) and all junior high students from the first to third year (21,737
      pupils) in Niigata City (population of 785,067) to examine the point prevalence
      of LBP, the lifetime prevalence, the gender differences, the age of first onset
      of LBP in third year of junior high school students, the duration, the presence
      of recurrent LBP or not, the trigger of LBP, and the influences of sports and
      physical activities. In addition, the severity of LBP was divided into three
      levels (level 1: no limitation in any activity; level 2: necessary to refrain
      from participating in sports and physical activities, and level 3: necessary to
      be absent from school) in order to examine the factors that contribute to severe
      LBP. The validity rate was 79.8% and the valid response rate was 98.8%. The point
      prevalence was 10.2% (52.3% male and 47.7% female) and the lifetime prevalence
      was 28.8% (48.5% male and 51.5% female). Both increased as the grade level
      increased and in third year of junior high school students, a point prevalence
      was seen in 15.2% while a lifetime prevalence was observed in 42.5%. About 90% of
      these students experienced first-time LBP during the first and third year of
      junior high school. Regarding the duration of LBP, 66.7% experienced it for less
      than 1 week, while 86.1% suffered from it for less than 1 month. The recurrence
      rate was 60.5%. Regarding the triggers of LBP, 23.7% of them reported the
      influence of sports and exercise such as club activities and physical education,
      13.5% reported trauma, while 55.6% reported no specific triggers associated with
      their LBP. The severity of LBP included 81.9% at level 1, 13.9% at level 2 and
      4.2% at level 3. It was revealed that LBP in childhood and adolescence is also a
      common complaint in Japan, and these findings are similar to previous studies
      conducted in Europe. LBP increased as the grade level increased and it appeared
      that the point and lifetime prevalence in adolescence are close to the same
      levels as those seen in the adulthood and there was a tendency to have more
      severe LBP in both cases who experienced pain for more than 1 month and those
      with recurrent LBP.

PMID- 18830639
TI  - MRI and MRA for evaluation of dissection of craniocerebral arteries: lessons from
      the medical literature.
AB  - MR imaging and MR angiography have become first-line imaging techniques in
      assessment of the patient with suspected dissection of the carotid and vertebral
      arteries. This review describes the advantages of these two techniques for
      diagnosis and describes diagnostic pitfalls.

PMID- 18830638
TI  - Percutaneous cervical nucleoplasty in the treatment of cervical disc herniation.
AB  - Percutaneous disc decompression procedures have been performed in the past.
      Various percutaneous techniques such as percutaneous discectomy, laser
      discectomy, and nucleoplasty have been successful. Our prospective study was
      directly to evaluate the results of percutaneous cervical nucleoplasty (PCN)
      surgery for cervical disc herniation, and illustrate the effectiveness of PCN in
      symptomatic patients who had cervical herniated discs. From July of 2002 to June
      of 2005, 126 consecutive patients with contained cervical disc herniations have
      presented at the authors' clinic and treated by PCN. The patients' gender
      distribution for PCN was 65 male, 61 female. The age of patients ranged from 34
      to 66 years (mean 51.9 +/- 10.2 years). The levels of involvement were 21 cases
      at C3-4, 30 cases at C4-5, 40 cases at C5-6, and 35 cases at C6-7. The clinical
      outcomes, pain reduction and the segment stability were all recorded during this
      study. A clinical outcome was quantified by the Macnab standard and using VAS.
      The angular displacement (AD) > or =11 degrees or horizontal displacement (HD) >
      or =3 mm was considered to be radiographically unstable. In the results of this
      study, puncture of the needle into the disc space was accurately performed under
      X-ray guidance in all cases. There was one case where the Perc-D Spine Wand had
      broken in the disc space during the procedure. The partial Perc-D Spine Wand,
      which had broken in the disc space could not be removed by the percutaneous
      cervical discectomy and thus remained there. There were no recurrent cases or
      complications in our series. Macnab standard results were excellent in 62 cases,
      good in 41 cases and fair in 23 cases. The rate of excellent and good was 83.73%.
      The VAS scores demonstrated statistically significant improvement in PCN at the 2
      week, 1, 3, 6, and 12-month follow-up visits when compared to preoperational
      values (P < 0.01). There were no cases of instability following the PCN
      procedure. There was no significant difference in stability either preoperatively
      or postoperatively (P > 0.05). Our findings confirm that PCN for the treatment of
      cervical disc herniation results in a good outcome without any tampering of the
      stability of the cervical spine. Hence, PCN as a procedure is safe, minimally
      invasive, less traumatic, requiring less time with an excellent clinical outcome.
      PCN should be performed for those patients who fail conservative medical
      management including medication, physical therapy, behavioral management,
      psychotherapy, and who are unwilling to undergo a more invasive technique such as
      spinal surgery.

PMID- 18830640
TI  - Cases from the Cleveland Clinic: cerebral venous sinus thrombosis presenting to
      the emergency department with worst headache of life.
AB  - A 31 year old woman presented with the worst headache of her life and was
      diagnosed with cerebral venous sinus thrombosis (CVST) by routine unenhanced
      computed tomography (CT) scan, subsequently confirmed with magnetic resonance
      imaging (MRI) and magnetic resonance venography (MRV). Awareness of this less
      common cause for acute neurological presentation in the Emergency setting is
      important; the imaging characteristics of CVST are reviewed.

PMID- 18830641
TI  - Perineal hernia.
AB  - Abdominal wall hernias are a common abdominal pathology with higher prevalence in
      our population. It is usually asymptomatic but complications such as
      strangulation, incarceration or bowel obstruction need early detection and
      emergency surgery. The purpose of this article is to describe the infrequent type
      of hernia, illustrate the imaging findings and review the differential diagnosis.
      A 76-year-old woman was admitted in the emergency room with abdominal pain,
      vomits and diarrhoea. At her admission, a colonoscopy was attempted to perform
      but it was not possible to go beyond the stenosis. A barium enema and a multi
      detector computed tomography (MDCT) were performed revealing a large mass in the
      left ischiorectal fossa, containing herniated loops of sigmoid colon adjacent to
      rectum. Abdominal wall hernias occur at areas of congenital or acquired weakness
      in the abdominal wall and are considered external hernias. MDCT is essential to
      identify wall hernias, make an accurate diagnosis and help for its clinical
      assessment. Knowing the radiological features of various types of abdominal
      hernias on MDCT and barium-enhanced radiographs allows confident diagnosis of
      these pathologies.

PMID- 18830642
TI  - Diffusion-weighted imaging of adnexal torsion.
AB  - We report the diffusion-weighted imaging findings (DWI) of a case with ovarian
      torsion. Magnetic resonance imaging revealed a large cyst within a non-enhancing
      ovary. DWI depicted restricted diffusion which in turn was found to be related
      with the infarction of the ovary in the laparoscopic salpingo-oophorectomy
      performed.

PMID- 18830643
TI  - Musculoskeletal: what is different in children? Jumped off bed; foot pain.

PMID- 18830644
TI  - Using sonography to assess lung recruitment in patients with acute respiratory
      distress syndrome.
AB  - The purpose of managing acute respiratory distress syndrome (ARDS) is "to open a
      closed lung" by increasing the airway pressure or changing the patient's
      position. Assessment of recruitment of atelectatic lung regions is necessary to
      have a correct management of mechanical ventilation and to be sure of positive
      end-expiratory pressure or prone position efficacy before their application. In
      fact, both of them could have collateral effects. Sonographic approach allows a
      dynamic evaluation of lung recruitment in patients affected by ARDS and it is
      easy to perform bedside. In particular, it is useful for patients too unstable to
      be moved to the CT room. Sonography is fast, cheap, and radiation free; thus, it
      can be repeated in order to monitor the evolution of ARDS. To our knowledge, the
      use of this technique in the setting of ARDS was never reported before.

PMID- 18830645
TI  - Skeletal trauma in children: what is different? : injury to left shoulder in a 13
      year-old boy.

PMID- 18830646
TI  - A review of stereotaxy and lysis for intracranial hemorrhage.
AB  - Intracranial hemorrhage represents a significant cause of human morbidity and
      mortality, leaving as many as 80% of patients either dead or disabled. Techniques
      for management of hemorrhage include optimal medical care, craniotomy, endoscopy,
      and stereotaxy. This work reviews the history of cranial stereotaxy for
      evacuation of nontraumatic hemorrhage beginning with techniques for mechanical
      disruption of the coagulated hemorrhage modeled after Archimedes screw. We
      discuss the properties of urokinase and tissue plasminogen activator, which have
      been utilized for lysis, and the outcomes after stereotactic fibrinolytic
      evacuation of intracerebral hemorrhage. The ongoing clinical trials evaluating
      the efficacy of stereotactic fibrinolysis are also discussed.

PMID- 18830647
TI  - Laccase-mediator system in the decolorization of different types of recalcitrant
      dyes.
AB  - Phloroglucinol, thymol, and violuric acid (VIO) were selected as laccase
      mediators after screening 14 different compounds with indigo carmine (indigoid
      dye) as a substrate. With the presence of these three mediators, a nearly
      complete decolorization (90-100%) was attained in 1 h. Thus, these three
      compounds were used as mediators for the decolorization of other four dyes. The
      results indicated that VIO was effective mediator in decolorization of Remazol
      brilliant blue R (RBBR, anthraquinoid dye) and Coomassie brilliant blue G-250
      (CBB, triphenylmethane dyes), and Acid red (diazo dye). In presence of VIO, the
      four dyes described above attained 70% decolorization. Thymol was able to mediate
      decolorization of RBBR and Azure A (heterocyclic dye). Phloroglucinol has no
      mediating capability in decolorization of the four dyes analyzed. Mediator
      concentration, pH, and copper ion have an effect on the decolorization of the
      RBBR. Our data suggested that the decolorization capabilities of laccase/mediator
      system were related to the types of mediator, the dye structure and
      decolorization condition.

PMID- 18830648
TI  - 1H MR spectroscopic imaging with short and long echo time to discriminate glycine
      in glial tumours.
AB  - OBJECT: To investigate glycine (Gly) concentrations in low- and high-grade
      gliomas based on (1)H MR spectroscopic imaging (MRSI) with short and long echo
      time (TE). Myoinositol (MI) and Gly appear at the same resonance frequency of
      3.56 ppm, but due to strong coupling the MI signal dephases more rapidly.
      Therefore, their contribution to the 3.56 ppm signal should be distinguishable
      comparing MRSI data acquired at short and long TE. MATERIALS AND METHODS: (1)H
      MRSI (TE = 30 and 144 ms) was performed at 3 T in 29 patients with
      histopathological confirmed World Health Organization (WHO) grade II-IV gliomas
      and in FIVE healthy subjects. All spectra from the gliomas revealed increase of
      the 3.56 ppm resonance in the short TE spectra. Signal intensities of Gly and MI
      were differentiated either by analysing the short to long TE ratio of the
      resonance or by performing a weighted difference. Gly concentrations were
      compared between high-grade (WHO III-IV) and low-grade gliomas. RESULTS: High
      grade gliomas showed significantly higher Gly concentrations compared to low
      grade gliomas. CONCLUSION: Appropriate data processing of short and long TE (1)H
      MRSI provides a tool to distinguish and to quantify Gly and MI concentrations in
      gliomas. As Gly seems to be a marker of malignancy, more dedicated spectroscopic
      methods to differentiate these metabolites are justified.

PMID- 18830649
TI  - Abstracts of ESMRMB 2008, 25th Annual Scientific Meeting of the European Society
      for Magnetic Resonance in Medicine and Biology. Valencia, Spain. October 2-4,
      2008.

PMID- 18830654
TI  - A method to detect progression of glaucoma using the multifocal visual evoked
      potential technique.
AB  - PURPOSE: To describe a method for monitoring progression of glaucoma using the
      multifocal visual evoked potential (mfVEP) technique. METHODS: Eighty-seven
      patients diagnosed with open-angle glaucoma were divided into two groups. Group
      I, comprised 43 patients who had a repeat mfVEP test within 50 days (mean 0.9 +/-
      0.5 months), and group II, 44 patients who had a repeat test after at least 6
      months (mean 20.7 +/- 9.7 months). Monocular mfVEPs were obtained using a 60
      sector pattern reversal dartboard display. Monocular and interocular analyses
      were performed. Data from the two visits were compared. The total number of
      abnormal test points with P < 5% within the visual field (total scores) and
      number of abnormal test points within a cluster (cluster size) were calculated.
      Data for group I provided a measure of test-retest variability independent of
      disease progression. Data for group II provided a possible measure of
      progression. RESULTS: The difference in the total scores for group II between
      visit 1 and visit 2 for the interocular and monocular comparison was significant
      (P < 0.05) as was the difference in cluster size for the interocular comparison
      (P < 0.05). Group I did not show a significant change in either total score or
      cluster size. CONCLUSION: The change in the total score and cluster size over
      time provides a possible method for assessing progression of glaucoma with the
      mfVEP technique.

PMID- 18830655
TI  - Clinical monitoring of torso deformities in scoliosis using structured splines
      models.
AB  - This paper describes the use of structured splines indices for the clinical
      monitoring of torso deformity in scoliosis. Structured splines indices are
      computed from the distribution of points of maximal curvature (dominant points)
      of an object. The suitability and robustness of the indices for this application
      is assessed by ascertaining their robustness to inevitable torso shape variations
      due to sway and breathing and the variability in their values relative to
      existing clinical measures of deformity. To assess the consistency of these
      indices with other indices in use for this application, they were used to assess
      the relative information contents of the front and back of the torso. Results
      show that structured splines indices are more robust than existing clinical
      measures for monitoring torso deformity in scoliosis. Results also show that the
      scoliosis information content ratio of the back torso to the front torso is three
      to one.

PMID- 18830656
TI  - Withdrawal reflexes examined during human gait by ground reaction forces: site
      and gait phase dependency.
AB  - The objective of this study was to investigate the modulation of the nociceptive
      withdrawal reflex during gait measured using Force Sensitive Resistors (FSR).
      Electrical stimulation was delivered to four locations on the sole of the foot at
      three different time points between heel-off and toe-off. Peak force changes were
      measured by FSRs attached to the big toe, distal to the first and fourth
      metatarsophalangeal joints, and the medial process of the calcaneus on both feet.
      Force changes were assessed in five gait sub-phases. The painful stimulation led
      to increased ipsilateral unloading (10 +/- 1 N) and contralateral loading (12 +/-
      1 N), which were dependent on stimulation site and phase. In contrast, the hallux
      of the ipsilateral foot plantar flexed, thus facilitating the push-off. The
      highest degree of plantar flexion (23 +/- 10 N; range, 8-44 N) was seen in the
      second double support phase following the stimulation. Site and phase modulation
      of the reflex were detected in the force signals from all selected anatomical
      landmarks. In the kinematic responses, both site and phase modulation were
      observed. For stimulations near toe-off, withdrawal was primarily accomplished by
      ankle dorsiflexion, while the strategy for stimulations at heel-off was flexion
      of the knee and hip joints.

PMID- 18830657
TI  - Molecular evolution of a steroid hydroxylating cytochrome P450 using a versatile
      steroid detection system for screening.
AB  - Molecular evolution is a powerful tool for improving or changing activities of
      enzymes for their use in biotechnological processes. Cytochromes P450 are highly
      interesting enzymes for biotechnological purposes because they are able to
      hydroxylate a broad variety of substrates with high regio- and stereoselectivity.
      One promising steroid hydroxylating cytochrome P450 for biotechnological
      applications is CYP106A2 from Bacillus megaterium ATCC 13368. It is one of a few
      known bacterial cytochromes P450 able to transform steroids such as progesterone
      and 11-deoxycortisol. CYP106A2 can be easily expressed in Escherichia coli with a
      high yield and can be reconstituted using the adrenal redox proteins, adrenodoxin
      and adrenodoxin reductase. We developed a simple screening assay for this system
      and performed random mutagenesis of CYP106A2, yielding variants with improved 11
      deoxycortisol and progesterone hydroxylation activity. After two generations of
      directed evolution, we were able to improve the k (cat)/K (m) of the 11
      deoxycortisol hydroxylation by a factor of more than four. At the same time
      progesterone conversion was improved about 1.4-fold. Mapping the mutations
      identified in catalytically improved CYP106A2 variants into the structure of a
      CYP106A2 model suggests that these mutations influence the mobility of the F/G
      loop, and the interaction with the redox partner adrenodoxin. The results show
      the evolution of a soluble steroid hydroxylase as a potential new catalyst for
      the production of steroidogenic compounds.

PMID- 18830658
TI  - The challenges for molecular nutrition research 3: comparative nutrigenomics
      research as a basis for entering the systems level.
AB  - Human nutrition and metabolism may serve as the paradigm for the complex
      interplay of the genome with its environment. The concept of nutrigenomics now
      enables science with new tools and comprehensive analytical techniques to
      investigate this interaction at all levels of the complexity of the organism.
      Moreover, nutrigenomics seeks to better define the homeostatic control
      mechanisms, identify the de-regulation in the early phases of diet-related
      diseases, and attempts to assess to what extent an individual's sensitizing
      genotype contributes to the overall health or disease state. In a comparative
      approach nutrigenomics uses biological systems of increasing complexity from
      yeast to mammalian models to define the general rules of metabolic and genetic
      mechanisms in adaptations to the nutritional environment. Powerful information
      technology, bioinformatics and knowledge management tools as well as new
      mathematical and computational approaches now make it possible to study these
      molecular mechanisms at the cellular, organ and whole organism level and take it
      on to modeling the processes in a "systems biology" approach. This review
      summarizes some of the concepts of a comparative approach to nutrigenomics
      research, identifies current lacks and proposes a concerted scientific effort to
      create the basis for nutritional systems biology.

PMID- 18830659
TI  - [Steps towards a symptom-based diagnosis of fibromyalgia syndrome. Symptom
      profiles of patients from different clinical settings].
AB  - BACKGROUND: A symptom-based diagnosis of fibromyalgia syndrome (FMS) without
      tender point examination is helpful for primary medical care. We tested whether a
      symptom-based diagnosis of FMS can be based on the symptoms of musculoskeletal
      pain and fatigue. METHODS: The most frequent and severe symptoms in FMS patients
      from four different settings (n= 464 from a self-help organization, n=162 from
      medical expertise, n= 33 from a private rheumatology practice, n=36 from a
      tertiary-care pain department) were assessed using the Giessen Subjective
      Complaints List GBB 24. The most frequent and severe symptoms were assessed and
      compared to those of a representative German population sample. A k-means cluster
      analysis was performed to identify sub-groups with and without additional
      vegetative symptoms within the total sample of FMS patients. RESULTS: The most
      frequent and severe symptoms in all four sub-samples were low back pain, limb
      pain and fatigue. The greatest mean differences between FMS patients and the
      general population were found in the subscales "limb pain" and "fatigue". Cluster
      analysis identified three sub-groups of patients which were all characterized by
      severe limb pain and fatigue, as well as varying degrees of vegetative symptoms.
      SUMMARY: Following the exclusion of inflammatory rheumatoid, endocrinological and
      neurological diseases, a symptom-based clinical diagnosis of FMS can be based on
      of the key symptoms of chronic widespread musculoskeletal pain, as well as
      chronic fatigue.

PMID- 18830662
TI  - Molecular studies on the microbial diversity associated with mining-impacted
      Coeur d'Alene River sediments.
AB  - The prokaryotic diversity associated with highly metal-contaminated sediment
      samples collected from the Coeur d'Alene River (CdAR) was investigated using a
      cultivation-independent approach. Bacterial community structure was studied by
      constructing an RNA polymerase beta subunit (rpoB) gene library. Phylogenetic
      analysis revealed that 75.8% of the rpoB clones were associated with beta
      Proteobacteria while the remaining 24.2% were with gamma-Proteobacteria. All
      phylotypes showed close similarity to previously reported cultivable lineages
      from metal or organic contaminant-rich environments. In an archaeal 16S rRNA gene
      library, 70% of the clones were affiliated to Crenarchaeota, while 30% belonged
      to Euryarchaeota. Most of the Euryarchaeota sequences were related to
      acetoclastic lineages belonging to Methanosarcinales. A single phylotype within
      the Euryarchaeota showed no association with cultivable euryarchaeotal lineages
      and might represent novel taxon. Diversity indices demonstrated greater diversity
      of Bacteria compared to Archaea in CdAR sediments. Sediment characterization by
      the X-ray fluorescence spectroscopy revealed high amount of toxic metals. To our
      knowledge, this is the first culture-independent survey on the prokaryotic
      diversity present in mining-impacted sediments of CdAR.

PMID- 18830663
TI  - Lymph node staging in esophageal adenocarcinoma with PET-CT based on a visual
      analysis and based on metabolic parameters.
AB  - BACKGROUND: In order to investigate the value of FDG positron emission tomography
      computed tomography (PET-CT), FDG PET (reviewed side-by-side with CT), and
      metabolic parameters in the assessment of lymph node status and prognosis.
      METHODS: Fifty-five subjects with lymph node positive (N1) and 26 subjects with
      lymph node negative (N0) disease were included. In the slice with the maximum FDG
      uptake of the tumor, the axial area of the primary tumor, the maximum diameter of
      the tumor, and the mean and maximum standardized uptake values were measured.
      RESULTS: Fused PET-CT correctly characterized 289 of 325 lymph node groups
      (accuracy 89%) compared to 273 of 325 with PET (accuracy 84%). In lymph node
      staging (N0 vs. N1), PET-CT (accuracy 83%) was more accurate than PET (accuracy
      78%). Among the metabolic parameters, the tumor diameter measured on PET-CT was
      the best predictor of lymph node stage (N0 vs. N1: accuracy 86%; threshold 25.5
      mm) and overall survival. However, the highest accuracy of lymph node staging (N0
      vs. N1) was achieved with the synergistic combination of visual analysis and
      primary tumor diameter measurements (accuracy 95%). CONCLUSIONS: PET-CT increases
      accuracy of lymph node staging in esophageal adenocarcinoma compared to PET. The
      primary tumor diameter further improves accuracy in lymph node staging and was
      shown to be an independent predictor of overall survival.

PMID- 18830664
TI  - Small RNA ArrF regulates the expression of sodB and feSII genes in Azotobacter
      vinelandii.
AB  - Azotobacter vinelandii contains a prrF-like sequence in a noncoding region of the
      chromosome. Like the Pseudomonas aeruginosa PrrF small RNA-encoding genes, the
      expression of the sequence, herein named arrF (Azotobacter regulatory RNA
      involving Fe), was increased 100-fold in wild-type cells in response to iron
      depletion. The level of ArrF was also increased to the same degree in the iron
      replete fur mutant, but down back to a wild-type level when this fur mutant was
      complemented with the wild-type fur gene. These results, with the location of
      arrF gene in a noncoding region, suggest that this gene encodes an iron
      responsive small RNA whose expression is negatively regulated by the Fur-Fe(2+)
      complex. Disruption of this arrF gene upregulated the expression of iron
      containing superoxide dismutase and FeSII protein, whereas fur mutation or iron
      depletion decreased the level of their transcript. A short region in the 5'
      untranslated region of each transcript was predicted to be quite complementary to
      the core sequence of ArrF, assuming that ArrF represses the expression of the
      genes under Fur control by an antisense RNA mechanism. However, unlike the P.
      aeruginosa PrrF that has extensive targets in the tricarboxylic acid cycle and
      glyoxylate cycle, ArrF had little effect on those genes. The findings that there
      is a poor overlap between ArrF and PrrF targets and that the FeSII gene, which is
      present only in the chromosome of nitrogen-fixing bacterial species, is
      controlled by ArrF suggest that ArrF might have unique targets, some of which are
      involved in N(2) fixation.

PMID- 18830665
TI  - Cold stress stimulates intracellular calcification by the coccolithophore,
      Emiliania huxleyi (Haptophyceae) under phosphate-deficient conditions.
AB  - Intracellular calcification by the coccolith-producing haptophyte Emiliania
      huxleyi (NIES 837) is regulated by various environmental factors. This study
      focused on the relationship between cold and phosphate-deficient stresses to
      elucidate how those factors control coccolith production. (45)Ca incorporation
      into coccoliths was more than 97% of the total (45)Ca incorporation by whole
      cells. In a batch culture, orthophosphate in the medium (final concentration,
      28.7 muM) was rapidly depleted within 3 days, and then extracellular alkaline
      phosphatase (AP) activity, an indicator of phosphate deprivation, increased
      during the stationary growth phase. The increase in AP activity was slightly
      higher at 20 degrees C than at 12 degrees C. The calcification started to
      increase earlier than AP activity, and the increase was much higher at 12 degrees
      C than at 20 degrees C. Such enhancement of calcification was suppressed by the
      addition of phosphate, while AP activity was also suppressed after a transient
      increase. These results suggest that phosphate deprivation is a trigger for
      calcification and that a rather long induction period is needed for calcification
      compared to the increase in AP activity. While calcification was greatly
      stimulated by cold stress, other cellular activities such as growth, phosphate
      utilization, and the induction of AP activity were suppressed. The stimulation of
      coccolith production by cold stress was minimal under phosphate-sufficient
      conditions. The high calcification activity estimated by (45)Ca incorporation was
      confirmed by morphological observations of coccoliths on the cell surface under
      bright-field and polarization microscopy. These results indicate that phosphate
      deprivation is the primary factor for stimulating coccolith production, and cold
      stress is a secondary acceleration factor that stimulates calcification under
      conditions of phosphate deprivation.

PMID- 18830666
TI  - Factors affecting axillary lymph node retrieval and assessment in breast cancer
      patients.
AB  - BACKGROUND: Breast cancer is the most common female cancer in North America.
      Axillary lymph node dissection (ALND) is important for staging, prognosis, and
      adjuvant treatment decisions. The purpose of this study was to identify factors
      that affect the number of lymph nodes (LN) retrieved in ALND for breast cancer.
      METHODS: All patients who underwent ALND for breast cancer at Sunnybrook Health
      Sciences Centre and Women's College Hospital between July 1999 and June 2006 were
      included. The number of LN retrieved was identified from pathology reports.
      Univariate and multivariate analysis was undertaken to identify variables
      influencing this outcome. RESULTS: 1084 patients were identified with a mean
      number of LN of 14.5. In multivariate analyses, significant covariates included
      sentinel LN biopsy (P = 0.011), degree of extranodal extension (P = 0.005), tumor
      grade (P = 0.058), and age (P = 0.043). Thirteen percent of the variation in LN
      yield was accounted for by institutional, provider, patient, and tumor related
      factors, leaving 87% attributable to inherent biological or other differences
      between patients. CONCLUSION: The yield of ALND may be influenced by multiple
      factors, often not related to the surgery. In settings where >10 LNs are
      routinely retrieved at ALND, biological variation between patients should be
      recognized as major a contributor to the LN yield. Adjuvant treatment decisions
      based on this outcome should take this into consideration.

PMID- 18830667
TI  - Why do patients with low-grade soft tissue sarcoma die?
AB  - INTRODUCTION: The patterns of failure and mechanisms of sarcoma-specific death
      are poorly characterized among the minority of patients with low-grade soft
      tissue sarcoma (STS) who succumb to disease. METHODS: Between 1982 and 2006,
      2,041 patients aged >or=16 years with low-grade STS of all sites were treated
      with curative intent and prospectively followed at a single institution. RESULTS:
      Among this cohort, 181 (9%) died from disease (DOD). Overall, 105 patients (58%)
      died from locally recurrent disease (DOLR), and 59 (32%) died from distant
      disease (DODR). In 17 patients (9%), the mechanism of sarcoma-related death could
      not be verified. DOD occurred at a median of 62 months, while median disease
      specific survival for the entire cohort was not reached. Median follow-up was 66
      months (range 2-431 months). On multivariate analysis, DOD was associated with
      site, size, and less than R0 resection. For DOLR, site, size, positive margins,
      liposarcoma histology, and local recurrence (by definition) were significant
      factors. For DODR, site, histology, and positive margins were not significant
      factors, while size and local recurrence were. Of DOLR, 80% were retroperitoneal,
      68% were liposarcoma, and only 2% were extremity. Conversely, of DODR, extremity
      (47%) and trunk (18%) were the most common sites, but histology was more variable
      [liposarcoma 35%, malignant fibrous histiocytoma (MFH) 20%, fibrosarcoma 12%,
      extraskeletal myxoid chondrosarcoma 10%]. High-grade recurrence rates were
      comparable between DOLR (27%) and DODR (25%). CONCLUSION: Among patients with low
      grade STS, DOD occurs in approximately 9% of patients. Nonextremity site, larger
      size, and less than R0 resection are the most important risk factors for DOD, and
      distinct patterns of recurrence and death are predicted by primary tumor site.

PMID- 18830668
TI  - Different patterns of lymphatic spread of sigmoid, rectosigmoid, and rectal
      cancers.
AB  - PURPOSE: We tried to evaluate the clinicopathological characteristics of
      rectosigmoid cancer compared with those of sigmoid and rectal cancer. METHODS: We
      collected data on patients who underwent curative resections for sigmoid (399; SC
      group), rectosigmoid (175; RS group), and upper rectal cancer (453; RA group)
      between June 1996 and December 2007. RESULTS: The mean distance from the anal
      verge was 12.5 cm for rectosigmoid cancer, 13 cm for sigmoid cancer, and 9.8 cm
      for rectal cancer. The most common metastatic lymph nodes were pararectal nodes
      for the RS and RA groups and sigmoid mesenteric lymph nodes for the SC group. In
      a comparison of categories N2 and N1 for SC and RA groups, the increase of the
      metastasis rate was similar for all lymph nodes groups. However, for the RS
      group, the increase of metastasis to pararectal nodes was prominent in the N2
      category. Overall recurrence and disease-free survival rate were not different
      among the groups. For stage III disease, the local recurrence rate was
      significantly higher in the RA group; the disease-free survival rate was higher
      in the SC group, and the RS group showed results similar to those of the RA
      group. CONCLUSION: Clinicopathological characteristics of rectosigmoid cancer
      were similar to those of sigmoid or rectal cancer. For lymphatic spreads, it was
      different from sigmoid or rectal cancer and more frequently metastasized to
      pararectal nodes. Oncologic results were slightly unfavorable to sigmoid colon,
      and showed data similar to those of rectal cancer. Therefore, rectosigmoid cancer
      was a "real" classification of colorectal cancer with unique lymphatic spread.

PMID- 18830669
TI  - Improving the accuracy of TNM staging in esophageal cancer: a pathological review
      of resected specimens.
AB  - BACKGROUND: Controversy exists over the Sixth Edition of the International Union
      Against Cancer (UICC) TNM staging system for esophageal cancer. Inclusion of
      additional information such as the number of metastatic lymph nodes and
      extracapsular lymph node invasion may improve the current staging system and lead
      to optimization of patient treatment. METHODS: All patients in Adelaide who
      underwent resection for esophageal cancer between 1997 and 2007 were identified
      from a prospective database. Two independent observers then reexamined all
      pathology slides from the original resection. Univariate and multivariate
      analysis was performed to identify significant prognostic factors. The goodness
      of fit and accuracy of additional prognostic factors were assessed, and the
      staging system was modified according to this information. RESULTS: There were
      240 patients (mean age, 62 years) who met the inclusion criteria. The 5-year
      overall survival rate was 36% (median, 24 months). Only histological grade and a
      refined pN stage were found to be independent prognostic factors that could then
      be used to improve current TNM staging. Subdivision of pN stage into three groups
      (0, 1-2, and >2 positive nodes) showed significant differences in 5-year survival
      between all three groups: 53% vs 27% vs 6%, respectively (P < .01). The optimal
      staging model was the same for patients who received neoadjuvant therapy and
      surgery (n = 116), and those who underwent surgery alone (n = 124). CONCLUSION: A
      staging model that incorporates a refined pN stage and histological grade appears
      to be more accurate than the current UICC-TNM staging system. This staging model
      is still applicable in patients who receive neoadjuvant therapy.

PMID- 18830670
TI  - Acetabular orientation: anterolateral approach in the supine position.
AB  - The anterolateral approach in the supine position provides excellent
      visualization of the acetabulum. The main advantage of the approach, a low
      dislocation rate, has been demonstrated in the literature, while the purported
      disadvantage of abductor dysfunction has not been clearly delineated in the
      literature. The technique requires meticulous attention to preservation of the
      gluteus medius and minimus tendons. Impingement and dislocation are avoided by
      careful attention to the preparation of acetabulum, critical assessment of the
      implanted components, and intraoperative trialing. Leg lengths are assessed
      through direct palpation of the malleoli. Routine use of postoperative hip
      precautions is not necessary when this approach is utilized. The anterolateral
      approach in the supine position allows for a reproducible result with a low
      dislocation rate. LEVEL OF EVIDENCE: Level V, therapeutic study. See the
      Guidelines for Authors for a complete description of levels of evidence.

PMID- 18830671
TI  - Immobilization modulates macrophage accumulation in tendon-bone healing.
AB  - Tendon-to-bone healing occurs by formation of a fibrous, scar tissue interface
      rather than regeneration of a normal insertion. Because inflammatory cells such
      as macrophages lead to formation of fibrous scar tissue, we hypothesized
      immobilization would allow resolution of acute inflammation and result in
      improved tendon-bone healing. We reconstructed the ACL of 60 Sprague-Dawley rats
      using a tendon autograft. An external fixation device was used to immobilize the
      surgically treated knee in 30 rats. We evaluated tendon-bone interface width,
      collagen fiber continuity, and new osteoid formation histologically.
      Immunohistochemistry was used to localize ED1+ and ED2+ macrophages at the tendon
      bone interface at 2 and 4 weeks. Biomechanical testing was performed at 4 weeks.
      Interface width was smaller and collagen fiber continuity was greater in the
      immobilized group. Immobilized animals exhibited fewer ED1+ macrophages at the
      healing interface at 2 and 4 weeks. In contrast, there were more ED2+ macrophages
      at the interface in the immobilized group at 2 weeks. Failure load and stiffness
      were similar between groups at 4 weeks. The data suggest early immobilization
      diminishes macrophage accumulation and may allow improved tendon-bone
      integration.

PMID- 18830672
TI  - Longitudinal analysis of a model to predict quality of life in prostate cancer
      patients and their spouses.
AB  - BACKGROUND/PURPOSE: This study examined a stress-coping model to assess whether
      baseline antecedent variables predicted subsequent appraisal and how that
      appraisal predicted coping and quality of life for prostate cancer patients and
      their spouses. METHODS: In a sample of 121 prostate cancer patient/spouse dyads,
      we assessed baseline antecedent variables (self-efficacy, current concerns, age,
      socioeconomic status, social support, communication, symptoms, phase of illness),
      4-month follow-up appraisal (negative appraisal, hopelessness, uncertainty), and
      8-month follow-up coping and mental and physical quality of life. Patients and
      spouses were assessed in a single integrated path model using structural equation
      modeling. RESULTS: The stress-coping model accounted for a significant amount of
      variance in mental and physical quality of life at 8 months for patients (40% and
      34%, respectively) and spouses (43% and 24%, respectively). Appraisal mediated
      the effect of several antecedent variables on quality of life. In addition,
      several partner effects (e.g., spouse variables influencing patient outcomes)
      were found. CONCLUSIONS: Prostate cancer patients need interventions that assist
      them to manage the effects of their disease. The stress-coping model suggests
      skills in several areas that could be improved. Programs need to include spouses
      because they also are negatively affected by the disease and can influence
      patient outcomes.

PMID- 18830673
TI  - BIM1, a bHLH protein involved in brassinosteroid signalling, controls Arabidopsis
      embryonic patterning via interaction with DORNROSCHEN and DORNROSCHEN-LIKE.
AB  - The BIM1 protein which has been implicated in brassinosteroid (BR) signal
      transduction was identified from a two hybrid screen using the N-terminus,
      including the AP2 domain, of the transcription factors DORNROESCHEN (DRN) and
      DORNROESCHEN-LIKE (DRNL) which control embryonic patterning. The protein-protein
      interaction between BIM1 and DRN or DRNL was confirmed by co-immunoprecipitation
      and for DRN also in vivo by bimolecular fluorescence complementation. BIM1 can
      also physically interact with PHAVOLUTA (PHV), another interaction partner of DRN
      and DRNL. Loss of BIM1 function results in embryo patterning defects at low
      penetrance, including cell division defects in the hypophyseal region and apical
      domain defects such as cotyledon fusion and polycotyledony, in addition to
      polyembryony. BIM1 expression overlaps with that of DRN and DRNL from early
      globular embryo stages onwards. Higher order mutants between bim1, drn, drnl and
      phv suggest that although BIM1 may act partially redundantly with DRN in early
      embryo development, all genes function within the same pathway determining
      cotyledon development, supporting the hypothesis that they participate in a
      multimeric transcription factor complex. A role of BIM1 in embryonic development
      not only implicates a function for brassinosteroids in this process, but the
      interaction of BIM1 with DRN, involved with auxin signalling, represents a
      possible point of hormonal crosstalk in embryonic patterning and the first
      example of an interaction of components of the auxin and BR signalling pathways.

PMID- 18830674
TI  - Fractures as predictors of excess mortality in the aged-a population-based study
      with a 12-year follow-up.
AB  - INTRODUCTION AND OBJECTIVE: The association between fractures and excess
      mortality in old age is ambiguous. The objective of this study was to analyze the
      long-term gender-specific association between fractures and mortality among older
      persons by controlling several survival related confounders. METHODS: A
      population-based prospective cohort study in the municipality of Lieto, south
      western Finland. Data on health, health behaviour, fractures, and mortality in
      482 men and 695 women aged 65 or older was collected from 1991 until 2002. The
      Cox Proportional Hazards regression model with fractures as time-dependent
      variables was used in the analyses. RESULTS: During the 12-year follow-up, 295
      (25%) persons sustained at least one fracture. Sustaining any kind of fracture
      was related to excess mortality both in men (age-adjusted Hazards Ratio, HR 2.2,
      95% confidence intervals, CI 1.6-3.1) and in women (HR 1.6, 95% CI 1.3-2.1). In
      the multivariate analyses, hip fractures in men (HR 8.1, 95% CI 4.4-14.9) and in
      women (HR 3.0, 95% CI 1.9-4.9), and proximal humerus fractures in men (HR 5.4,
      95% CI 1.6-17.7) were related to increased mortality. CONCLUSION: A hip fracture
      was a powerful independent predictor of long-term excess mortality in both
      genders but the risk in men was more than 2-fold compared to women. Proximal
      humerus fractures were associated with increased mortality in men. Actions to
      improve prevention, acute care and rehabilitation of fractures are needed in
      order to reduce excess mortality in older people.

PMID- 18830675
TI  - The impact of RNA interference of the subolesin and voraxin genes in male
      Amblyomma hebraeum (Acari: Ixodidae) on female engorgement and oviposition.
AB  - Reducing or replacing the use of chemical pesticides for tick control is a
      desirable goal. The most promising approach would be to develop vaccines that
      protect hosts against tick infestation. Antigens suitable for the development of
      anti-tick vaccines will likely be those essential for vital physiological
      processes, and in particular those directly involved in feeding and reproduction.
      In this study genes from Amblyomma hebraeum Koch that encode for subolesin and
      voraxin were studied in male ticks by RNA interference (RNAi). Males (unfed or
      fed) were injected with dsRNA of (1) subolesin, (2) voraxin, (3) subolesin plus
      voraxin or (4) injection buffer, after which they were held off-host overnight
      and then allowed to feed on rabbits together with normal female A. hebraeum.
      Females that fed together with male ticks injected with subolesin or subolesin +
      voraxin dsRNA had a higher rate of mortality, weighed substantially less and
      produced a smaller egg mass than the controls. However, females feeding with
      males injected with voraxin dsRNA alone were not significantly different from the
      controls with respect to mortality, engorged weight or fecundity. However, as
      assessed by semi-quantitative RT-PCR, voraxin was not silenced in this study, the
      reasons for which remain unknown. The results of this study suggest that A.
      hebraeum subolesin is worthy of further testing as a candidate tick vaccine
      antigen.

PMID- 18830676
TI  - Pregnancy weight gain is not associated with maternal or mixed umbilical cord
      estrogen and androgen concentrations.
AB  - The association of maternal weight gain with serum hormone concentrations was
      explored in 75 women who had healthy, singleton pregnancies. Estradiol, estriol,
      estrone, androstenedione, testosterone, dehydroepiandrosterone (DHEA), and DHEA
      sulfate concentrations were measured both in maternal and mixed umbilical cord
      serum to assess hormone levels in both the maternal and fetal circulation at
      delivery. Our data show no association of maternal or cord steroid hormone
      concentrations with pregnancy weight gain. Increased exposure to steroid
      hormones, especially estrogens, during pregnancy has been hypothesized to play a
      role in subsequent breast cancer risk for both mother and female offspring. Our
      results are not consistent with an effect of pregnancy weight gain being mediated
      by this pathway as reflected by hormone concentrations at the end of pregnancy.

PMID- 18830677
TI  - Meiotic behaviour of individual chromosomes of Festuca pratensis in tetraploid
      Lolium multiflorum.
AB  - Intergeneric hybrids of fescues (Festuca spp.) and ryegrasses (Lolium spp.) are
      unique for the ability of their chromosomes to pair essentially freely in meiotic
      metaphase I (MI). At the same time, their chromosomes can be readily recognized
      by genomic in-situ hybridization (GISH). Past genome-wide observations suggested
      that this homoeologous pairing was not completely random. In this study we extend
      the analysis to all seven individual chromosomes of F. pratensis introgressed
      into autotetraploid L. multiflorum and show that for any F. pratensis chromosome
      the choice of an MI pairing partner depends on the identity of the remaining
      chromosomes present in the quadruplet. In monosomic introgressions, the choice of
      a homologous or homoeologous partner was completely random; in disomics there was
      a slight preference for homologous pairing. Pairing preference was similar for
      each chromosome, suggesting that pairing affinity of all chromosomes is
      essentially the same and no structural rearrangements differentiate the two
      genera. Homoeologous crossover rates for individual chromosomes were similar and
      they were consistently lower than expected on the basis of the MI pairing. High
      homoeologous MI pairing in these hybrids may be due to a very permissive system
      of chromosome pairing control that overlooks differences between the parental
      chromosomes. Given the ease of genome discrimination by GISH in the Lolium
      Festuca hybrids, the differences in repetitive DNA sequences must be substantial.
      On the other hand, it appears just as likely that while the DNA repeats diverged
      markedly during evolution, the sequences involved in chromosome pairing have been
      conserved enough to facilitate regular pairing partner recognition and crossing
      over.

PMID- 18830678
TI  - A novel method for the synthesis of substituted 3,4-dihydrocoumarin derivatives
      via isocyanide-based three-component reaction.
AB  - A new one-pot procedure for the efficient synthesis of novel 3,4-dihydrocoumarin
      derivatives using commercially available substituted 2-hydroxybenzaldehydes,
      Meldrum's acid, and isocyanides by a three-component condensation reaction in
      dichloromethane at room temperature without using any catalysts and activation
      was developed.

PMID- 18830679
TI  - Three-component one-pot synthesis of 4,6-diarylpyrimidin- 2(1H)-ones under
      solvent-free conditions in the presence of sulfamic acid as a green and reusable
      catalyst.
AB  - A rapid and efficient one-pot method for the synthesis of 4,6-diarylpyrimidin
      2(1H)-ones and related heterocycles is described. The condensation of
      acetophenone derivatives, aldehydes and urea in the presence of sulfamic acid was
      employed to synthesize a variety of pyrimidinones in moderate to excellent
      yields. The scope and limitations of this method are described.

PMID- 18830680
TI  - Availability of subfertile transgenic rats expressing the c-myc gene as
      recipients for spermatogonial transplantation.
AB  - The spermatogonial transplantation system was applied to evaluate stem cell
      kinetics and niche quality and to produce gene-modified animals using the stem
      cells after homologous recombination-based selection. This study was designed to
      determine whether the transplanted spermatogonia were able to proliferate and
      differentiate in male rats expressing the c-myc transgene under control of the
      human metallothionein IIA promoter (MT-myc Tg rats). Donor testicular cells were
      prepared from heterozygous chicken beta actin (CAG)/enhanced green fluorescent
      protein (EGFP)-transgenic rats (EGFP Tg rats) during the second week after birth
      and injected into the seminiferous tubules of the MT-myc Tg rats (line-A and -B;
      both subfertile) or rats pretreated with busulfan to remove endogenous
      spermatogonia. Three to four months after transplantation, cell colonies with
      EGFP fluorescence were detected in 36% (4/11), 40% (8/20), and 71% (5/7) of the
      transplanted testes in line-A MT-myc Tg rats, line-B MT-myc Tg rats, and busulfan
      treated rats, respectively. No EGFP-positive colonies were detected when wild
      type male rats were used as recipients (0/7; testis-basis). The histopathological
      and immunofluorescent examination of the serial sections from the transplanted
      testes showed normal spermatogenesis of the donor spermatogonia, but atrophy of
      the recipient seminiferous tubules. Microinsemination with round spermatids and
      mature spermatozoa derived from EGFP-positive testes in line-A rats resulted 26%
      (10/39 transferred) and 23% (11/48 transferred) full-term offspring,
      respectively. Thus, the MT-myc Tg male rats were suitable as potent recipients
      for spermatogonial transplantation without any chemical pretreatment to remove
      the endogenous spermatogonia.

PMID- 18830681
TI  - Assessing the role of stress signalling via p38 MAP kinase in the premature
      senescence of ataxia telangiectasia and Werner syndrome fibroblasts.
AB  - The premature ageing ataxia telangiectasia (AT) and Werner syndromes (WS) are
      associated with accelerated cellular ageing. Young WS fibroblasts have an aged
      appearance and activated p38 MAP kinase, and treatment with the p38 inhibitor
      SB230580 extends their lifespan to within the normal range. SB203580 also extends
      the replicative lifespan of normal adult dermal fibroblasts, however, the effect
      is much reduced when compared to WS cells, suggesting that WS fibroblasts undergo
      a form of stress-induced premature senescence (SIPS). A small lifespan extension
      is seen in AT cells, which is not significant compared to normal fibroblasts, and
      the majority of young AT cells do not have an aged appearance and lack p38
      activation, suggesting that the premature ageing does not result from SIPS. The
      lack of p38 activation is supported by the clinical manifestation, since AT is
      not associated with inflammatory disease, whereas WS individuals are predisposed
      to atherosclerosis, type II diabetes and osteoporosis, conditions known to be
      associated with p38 activation.

PMID- 18830682
TI  - Age- and sex-related analysis of methylation of 5'-upstream sequences of Fmr-1
      gene in mouse brain and modulation by sex steroid hormones.
AB  - Fmr-1 gene is implicated in synaptic plasticity and thereby learning, memory and
      cognition, and methylation of Fmr-1 gene is necessary for memory development that
      is an age-dependent phenomenon. Aging in general has been reported to affect
      methylation of gene, however, nothing is known on the age dependent variation in
      methylation of Fmr-1 gene. Using the brain tissues from male and female mice of
      various age groups and sex steroid hormones (testosterone or 17beta-estradiol) as
      modulators, restriction enzymes Hpa II and Msp I and Southern blotting technique,
      we studied methylation of 5'-upstream sequences of Fmr-1 gene. Our data reveal
      that the methylation of the 5'-upstream sequences that include CpG islands in
      promoter and 5'-untraslated region (5'-UTR) gradually increases due to advancing
      age in both the sexes. 17beta-estradiol lowers the methylation significantly in
      the brain of mouse of both male and female mouse in age-dependent manner where as
      testosterone does not affect it appreciably. The alteration in the methylation
      may be attributed to altered DNA methyl transferase (DNMT) activity as the age
      increases from young to old, and the 17beta-estradiol may down regulate the DNMT
      activity in both the age and sex groups whereas the testosterone may not have
      similar effect on DNMT. Down regulation of methylation of Fmr-1 CpG island and/or
      5'-UTR by 17beta-estradiol might lead to derepression of Fmr-1 gene especially in
      old age. This finding on Fmr-1 methylation is novel and it might have
      implications in understanding fragile X related disorders and age-dependent
      alteration in LTP and LTD.

PMID- 18830683
TI  - Suppression of the aging-associated decline in physical performance by a
      combination of resveratrol intake and habitual exercise in senescence-accelerated
      mice.
AB  - The decline in physical performance with increasing age is a crucial problem in
      our aging society. We examined the effects of resveratrol, a natural polyphenolic
      compound present in grapes, in combination with habitual exercise on the aging
      associated decline in physical performance in senescence-accelerated prone mice
      (SAMP1). The endurance capacity of SAMP1 mice undergoing an exercise regimen
      (SAMP1-Ex) decreased over 12 weeks whereas that of SAMP1 mice fed 0.2% (w/w)
      resveratrol along with exercise (SAMP1-ExRes) remained significantly higher. In
      the SAMP1-ExRes group, there was a significant increase in oxygen consumption and
      skeletal muscle mRNA levels of mitochondrial function-related enzymes. These
      results suggest that the intake of resveratrol, together with habitual exercise,
      is beneficial for suppressing the aging-related decline in physical performance
      and that these effects are attributable, at least in part, to improved
      mitochondrial function in skeletal muscle.

PMID- 18830684
TI  - Cupriavidus metallidurans: evolution of a metal-resistant bacterium.
AB  - Cupriavidus metallidurans CH34 has gained increasing interest as a model organism
      for heavy metal detoxification and for biotechnological purposes. Resistance of
      this bacterium to transition metal cations is predominantly based on metal
      resistance determinants that contain genes for RND (resistance, nodulation, and
      cell division protein family) proteins. These are part of transenvelope protein
      complexes, which seem to detoxify the periplasm by export of toxic metal cations
      from the periplasm to the outside. Strain CH34 contains 12 predicted RND proteins
      belonging to a protein family of heavy metal exporters. Together with many efflux
      systems that detoxify the cytoplasm, regulators and possible metal-binding
      proteins, RND proteins mediate an efficient defense against transition metal
      cations. To shed some light into the origin of genes encoding these proteins, the
      genomes of C. metallidurans CH34 and six related proteobacteria were investigated
      for occurrence of orthologous and paralogous proteins involved in metal
      resistance. Strain CH34 was not much different from the other six bacteria when
      the total content of transport proteins was compared but CH34 had significantly
      more putative transition metal transport systems than the other bacteria. The
      genes for these systems are located on its chromosome 2 but especially on
      plasmids pMOL28 and pMOL30. Cobalt-nickel and chromate resistance determinants
      located on plasmid pMOL28 evolved by gene duplication and horizontal gene
      transfer events, leading to a better adaptation of strain CH34 to serpentine-like
      soils. The czc cobalt-zinc-cadmium resistance determinant, located on plasmid
      pMOL30 in addition copper, lead and mercury resistance determinants, arose by
      duplication of a czcICAB core determinant on chromosome 2, plus addition of the
      czcN gene upstream and the genes czcD, czcRS, czcE downstream of czcICBA. C.
      metallidurans apparently evolved metal resistance by horizontal acquisition and
      by duplication of genes for transition metal efflux, mostly on the two plasmids,
      and decreased the number of uptake systems for those metals.

PMID- 18830686
TI  - Duchenne muscular dystrophy; a cardiomyopathy that can be prevented?

PMID- 18830685
TI  - Photosystem II: The machinery of photosynthetic water splitting.
AB  - This review summarizes our current state of knowledge on the structural
      organization and functional pattern of photosynthetic water splitting in the
      multimeric Photosystem II (PS II) complex, which acts as a light-driven water:
      plastoquinone-oxidoreductase. The overall process comprises three types of
      reaction sequences: (1) photon absorption and excited singlet state trapping by
      charge separation leading to the ion radical pair [Formula: see text] formation,
      (2) oxidative water splitting into four protons and molecular dioxygen at the
      water oxidizing complex (WOC) with P680+* as driving force and tyrosine Y(Z) as
      intermediary redox carrier, and (3) reduction of plastoquinone to plastoquinol at
      the special Q(B) binding site with Q(A)-* acting as reductant. Based on recent
      progress in structure analysis and using new theoretical approaches the mechanism
      of reaction sequence (1) is discussed with special emphasis on the excited energy
      transfer pathways and the sequence of charge transfer steps: [Formula: see text]
      where (1)(RC-PC)* denotes the excited singlet state (1)P680* of the reaction
      centre pigment complex. The structure of the catalytic Mn(4)O(X)Ca cluster of the
      WOC and the four step reaction sequence leading to oxidative water splitting are
      described and problems arising for the electronic configuration, in particular
      for the nature of redox state S(3), are discussed. The unravelling of the mode of
      O-O bond formation is of key relevance for understanding the mechanism of the
      process. This problem is not yet solved. A multistate model is proposed for S(3)
      and the functional role of proton shifts and hydrogen bond network(s) is
      emphasized. Analogously, the structure of the Q(B) site for PQ reduction to
      PQH(2) and the energetic and kinetics of the two step redox reaction sequence are
      described. Furthermore, the relevance of the protein dynamics and the role of
      water molecules for its flexibility are briefly outlined. We end this review by
      presenting future perspectives on the water oxidation process.

PMID- 18830687
TI  - Affinity purification of trypsin inhibitor with anti-Aspergillus flavus activity
      from cultivated and wild soybean.
AB  - Trypsin inhibitors (TI) from wild-type soybean (Glycine soya) (WBTI) and
      domesticated soybean (Glycine max) (SBTI) were purified using prepared chitosan
      resin-trypsin as filler on the affinity chromatography column. The SBTI/WBTI
      purification fold by affinity chromatography was 718- and 279-fold, with the
      activity recovery of 62% and 59%, respectively. It was found that SBTI and WBTI
      exerted a strong inhibition of Aspergillus. flavus growth, with IC(50) of 1.6 and
      1.0 micromol/l. This growth inhibition was possibly the result of the inhibition
      on alpha-amylase activity of A. flavus by both the SBTI and WBTI. This was
      further supported by the fact that in the presence of SBTI and WBTI at 9.0 and
      6.0 microg/g (peanut) on peanuts inhibited the germination and growth of A.
      flavus. Accordingly, characterization of the mode of action of SBTI and WBTI
      could constitute a first step leading to resistance to A. flavus invasion.

PMID- 18830688
TI  - Variability of the mitochondrial SSU rDNA of Nomuraea species and other
      entomopathogenic fungi from hypocreales.
AB  - Hypocrealean arthropod pathogenic fungi have profound impact on the regulation of
      agricultural and medical pests. However, until now the genetic and phylogenetic
      relationships among species have not been clarified, such studies could clarify
      host specificity relationships and define species boundaries. Our purpose was to
      compare the sequences of the mitochondrial SSU rDNA fragments from several
      mitosporic entomopathogenic Hypocreales to infer relationships among them and to
      evaluate the possibility to use these sequences as species diagnostic tool in
      addition to the more commonly studied sequences of nuclear SSU rDNA. The SSU mt
      rDNA proved to be useful to help in differentiation of species inside several
      genera. Clusters obtained with Parsimony, Bayesian, and Maximum Likelihood
      analyses were congruent with a new classification of the Clavicipitaceae (Sung et
      al. Stud Mycol. 2007;57:5-59) in which the anamorphic genera Nomuraea and
      Metarhizium species remain in the Clavicipitaceae and Isaria species sequenced
      here are assigned to the family Cordycipitaceae. Mitochondrial genomic
      information indicates the same general pattern of relationships demonstrated by
      nuclear gene sequences.

PMID- 18830689
TI  - The effect of cryopreservation or heating on the mechanical properties and
      histomorphology of rat bone-patellar tendon-bone.
AB  - The effects of cryopreservation on tendon allograft have been reported, but
      remain unclear, particularly the potential effects on mechanical properties and
      histological changes by ice crystal formation. There are also few studies about
      effects of heating for sterilization of tendon. We evaluated the effect of
      cryopreservation or heating on the mechanical properties and histomorphology of
      rat bone-patellar tendon-bones (BTBs). BTBs were processed by cryopreservation at
      -80 degrees C for 3 weeks, or heating at 80 degrees C for 10 min. Tensile testing
      and histomorphological examination were performed. The cryopreservation of
      tendons showed less influences on their mechanical properties. When cryopreserved
      BTBs in frozen state were fixed by freeze-substitution method, many spaces were
      observed in interfibrillar substances. These results suggest that the collagen
      fibers of cryopreserved tendons were histomorphologically affected by ice
      crystals. The heating of tendons completely destroyed the collagen fibers of the
      tendons and is therefore thought to be inappropriate for the sterilization of
      BTBs.

PMID- 18830690
TI  - Brand name logo recognition of fast food and healthy food among children.
AB  - The fast food industry has been increasingly criticized for creating brand
      loyalty in young consumers. Food marketers are well versed in reaching children
      and youth given the importance of brand loyalty on future food purchasing
      behavior. In addition, food marketers are increasingly targeting the Hispanic
      population given their growing spending power. The fast food industry is among
      the leaders in reaching youth and ethnic minorities through their marketing
      efforts. The primary objective of this study was to determine if young children
      recognized fast food restaurant logos at a higher rate than other food brands.
      Methods Children (n = 155; 53% male; 87% Hispanic) ages 4-8 years were recruited
      from elementary schools and asked to match 10 logo cards to products depicted on
      a game board. Parents completed a survey assessing demographic and psychosocial
      characteristics associated with a healthy lifestyle in the home. Results Older
      children and children who were overweight were significantly more likely to
      recognize fast food restaurant logos than other food logos. Moreover, parents'
      psychosocial and socio-demographic characteristics were associated with the type
      of food logo recognized by the children. Conclusions Children's high recognition
      of fast food restaurant logos may reflect greater exposure to fast food
      advertisements. Families' socio-demographic characteristics play a role in
      children's recognition of food logos.

PMID- 18830691
TI  - The roles of parenting, church attendance, and depression in adolescent smoking.
AB  - The aim of the present study was to identify contextual factors related to
      smoking among urban African-American and White adolescents. We administered a
      survey assessing demographic and psychosocial variables to 299 adolescents in an
      urban pediatric clinic in the Midwest. Results indicated that being female, older
      age, lower academic performance, depressive symptoms, less frequent church
      attendance, parental smoking, and parental attitudes toward smoking were related
      to adolescent smoking. After controlling for demographics, the multivariate model
      predicting adolescent smoking included depressive symptoms, less frequent church
      attendance, and parental disapproval of smoking. Given these findings, efforts to
      decrease adolescent smoking may be enhanced by attending to depressive symptoms
      demonstrated by adolescents as well as contextual factors including parental
      attitudes and church attendance.

PMID- 18830692
TI  - A chemically explicit model for the mechanism of proton pumping in heme-copper
      oxidases.
AB  - A mechanism for proton pumping is described that is based on chemiosmotic
      principles and the detailed molecular structures now available for cytochrome
      oxidases. The importance of conserved water positions and a step-wise gated
      process of proton translocation is emphasized, where discrete electron transfer
      events are coupled to proton uptake and expulsion. The trajectory of each pumped
      proton is the same for all four substrate electrons. An essential role for the
      His-Tyr cross-linked species is discussed, in gating of the D- and K-channels and
      as an acceptor/donor of electrons and protons at the binuclear center.

PMID- 18830693
TI  - Stimulated intrauterine insemination (SIUI) and donor insemination (DI) as first
      line management for a selected subfertile population: the Manchester experience.
AB  - PURPOSE: The objective of our study is to investigate the optimum number of
      stimulated intrauterine insemination (SIUI) or donor insemination (DI) cycles
      that can be offered to the couples prior to in vitro fertilization (IVF) or
      intracytoplasmic sperm injection (ICSI) in a tertiary referral unit for assisted
      reproduction. METHODS: This is a retrospective analysis of 408 SIUI and 704 DI
      cycles performed in a tertiary referral unit for assisted reproduction. SIUI's
      were performed by controlled ovarian hyperstimulation and ovulation induction
      followed by insemination 36 h later. DI's were performed in natural or stimulated
      cycles after thawing frozen donor sperm. The main outcome measured was cumulative
      live birth rate (CLBR) per couple. RESULTS: A maximum CLBR of 26.1% was achieved
      after the fourth cycle of SIUI. The CLBR of DI increased to 60.1% in the sixth
      cycle. CONCLUSIONS: This study, in line with a number of other studies, is unable
      to demonstrate unequivocally whether increasing numbers of IUI or DI cycles are
      justified clinically or financially. There is a need for larger datasets from
      multiple centres along with rigorous randomised trials to compare treatment
      pathways. Until then, the resources spent on the provision of extra SIUI cycles
      may be better utilized by early referral to IVF.

PMID- 18830694
TI  - Tamoxifen induces regression of estradiol-induced mammary cancer in the ACI.COP
      Ept2 rat model.
AB  - The ACI rat is a unique model of human breast cancer in that mammary cancers are
      induced by estrogen without carcinogens, irradiation, xenografts or transgenic
      manipulations. We sought to characterize mammary cancers in a congenic variant of
      the ACI rat, the ACI.COP-Ept2. All rats with estradiol implants developed mammary
      cancers in 5-7 months. Rats bearing estradiol-induced mammary cancers were
      treated with tamoxifen for three weeks. Tamoxifen reduced tumor mass, measured by
      magnetic resonance imaging, by 89%. Tumors expressed estrogen receptors (ER),
      progesterone receptor (PR), and Erbb2. ERalpha and PR were overexpressed in tumor
      compared to adjacent non-tumor mammary gland. Thus, this model is highly relevant
      to hormone responsive human breast cancers.

PMID- 18830695
TI  - Equivalent charge source model based iterative maximum neighbor weight for sparse
      EEG source localization.
AB  - How to localize the neural electric activities within brain effectively and
      precisely from the scalp electroencephalogram (EEG) recordings is a critical
      issue for current study in clinical neurology and cognitive neuroscience. In this
      paper, based on the charge source model and the iterative re-weighted strategy,
      proposed is a new maximum neighbor weight based iterative sparse source imaging
      method, termed as CMOSS (Charge source model based Maximum neighbOr weight Sparse
      Solution). Different from the weight used in focal underdetermined system solver
      (FOCUSS) where the weight for each point in the discrete solution space is
      independently updated in iterations, the new designed weight for each point in
      each iteration is determined by the source solution of the last iteration at both
      the point and its neighbors. Using such a new weight, the next iteration may have
      a bigger chance to rectify the local source location bias existed in the previous
      iteration solution. The simulation studies with comparison to FOCUSS and LORETA
      for various source configurations were conducted on a realistic 3-shell head
      model, and the results confirmed the validation of CMOSS for sparse EEG source
      localization. Finally, CMOSS was applied to localize sources elicited in a visual
      stimuli experiment, and the result was consistent with those source areas
      involved in visual processing reported in previous studies.

PMID- 18830696
TI  - Development of high throughput optical sensor array for on-line pH monitoring in
      micro-scale cell culture environment.
AB  - On-line pH detection of cell culture environment is necessary in a bioprocess or
      tissue engineering. Devices by means of electrochemical mechanisms for this
      purpose have been reported to be less suitable compared with optical-based
      sensing principles. More recently, some non-invasive optical sensing systems have
      been proposed for online pH monitoring of cell culture environment. However,
      these devices are not for multi-target pH monitoring purpose, and are large in
      scale and thus not appropriate for the pH monitoring at a micro scale such as in
      microbioreactor or microfluidic-based cell culture platform. To tackle these
      issues, an optical fiber sensor array for on-line pH monitoring was proposed
      using microfluidic technology. The working principle is based on the optical
      absorption of phenol red normally contained in culture medium. Different from
      other device of the similar working principle, the proposed device requires less
      liquid volume (less than 0.8 microl), is non-invasive, and particularly can be
      configured as an array for high throughput pH monitoring. The present device has
      been optimized for the shape of detection chamber in a microfluidic chip with the
      aid of computational fluid dynamics (CFD) simulation, to avoid flow dead zone and
      thus to reduce the response time of detection. Both simulation and experimental
      results revealed that the design of oval detection chamber (axis, 1.5 and 2.0 mm)
      can considerably reduce the response time. Preliminary test has proved that the
      optical pH detection device is able to detect pH with average detection
      sensitivity of 0.83 V/pH in the pH range of 6.8-7.8, which is normally
      experienced in mammalian cell culture.

PMID- 18830697
TI  - The BMC ACCESS project: the development of a medically enhanced safe haven
      shelter.
AB  - This paper describes the development and implementation of the Boston Medical
      Center (BMC) Advanced Clinical Capacity for Engagement, Safety, and Services
      Project. In October 2002, the BMC Division of Psychiatry became the first such
      entity to open a Safe Haven shelter for people who are chronically homeless,
      struggling with severe mental illness, and actively substance abusing. The low
      demand Safe Haven model targets the most difficult to reach population and serves
      as a "portal of entry" to the mental health and addiction service systems. In
      this paper, the process by which this blended funded, multi-level collaboration,
      consisting of a medical center, state, city, local, and community-based consumer
      organizations, was created and is maintained, as well as the clinical model of
      care is described. Lessons learned from creating the Safe Haven Shelter and the
      development and implementation of the consumer-informed evaluation are discussed
      as well as implications for future work with this population.

PMID- 18830698
TI  - Manufactured aluminum oxide nanoparticles decrease expression of tight junction
      proteins in brain vasculature.
AB  - Manufactured nanoparticles of aluminum oxide (nano-alumina) have been widely used
      in the environment; however, their potential toxicity provides a growing concern
      for human health. The present study focuses on the hypothesis that nano-alumina
      can affect the blood-brain barrier and induce endothelial toxicity. In the first
      series of experiments, human brain microvascular endothelial cells (HBMEC) were
      exposed to alumina and control nanoparticles in dose- and time-responsive
      manners. Treatment with nano-alumina markedly reduced HBMEC viability, altered
      mitochondrial potential, increased cellular oxidation, and decreased tight
      junction protein expression as compared to control nanoparticles. Alterations of
      tight junction protein levels were prevented by cellular enrichment with
      glutathione. In the second series of experiments, rats were infused with nano
      alumina at the dose of 29 mg/kg and the brains were stained for expression of
      tight junction proteins. Treatment with nano-alumina resulted in a marked
      fragmentation and disruption of integrity of claudin-5 and occludin. These
      results indicate that cerebral vasculature can be affected by nano-alumina. In
      addition, our data indicate that alterations of mitochondrial functions may be
      the underlying mechanism of nano-alumina toxicity.

PMID- 18830700
TI  - [Recommendations on the use of rituximab for patients with rheumatoid arthritis].

PMID- 18830699
TI  - The perioperative management of pain from intracranial surgery.
AB  - Analgesic therapy following intracranial procedures remains a source of concern
      and controversy. Although opioids are the mainstay of the "balanced" general
      anesthetic techniques frequently used during intracranial procedures,
      neurosurgeons and others have been reluctant to administer opioid analgesics to
      patients following such procedures. This practice is supported by the concern
      that the sedation and miosis associated with opioid administration could mask the
      early signs of intracranial catastrophe, or even exacerbate it through decreased
      ventilatory drive, elevated arterial carbon dioxide levels, and increased
      cerebral blood flow. This reluctance to use opioids following intracranial
      surgery is enabled by decades of training and anecdote emphasizing that pain is
      minimal following these procedures. However, recent data suggests otherwise, and
      raises the question of how to provide safe and effective analgesia for these
      patients. Here, this data is reviewed along with the relevant pain pathways,
      analgesic drugs and techniques, and the available data on their use following
      intracranial surgery. Although pain following intracranial surgery appears to be
      more intense than initially believed, it is readily treated safely and
      effectively with techniques that have proven useful following other types of
      surgery, including patient-controlled administration of opioids. The use of
      multimodal analgesic therapy is emphasized not only for its effectiveness, but to
      reduce dosages and, therefore, side effects, primarily of the opioids, that could
      be of legitimate concern to physicians and affect the comfort of their patients.

PMID- 18830701
TI  - Nasopharyngeal carcinoma: our experience.
AB  - The objectives of our study were to characterize nasopharyngeal carcinoma
      patients in the Portuguese Institute of Oncology Hospital in Lisbon (IPOLFG) and
      identify the main factors that interfere with patients survival rate. We
      performed a retrospective study involving 157 patients (65% male and 35% female)
      between the years 2000 and 2005, and a histological classification according to
      Health World Organization. We constructed a Kaplan-Meier survival curve for the
      studied patients and evaluated the significance of the different studied factors
      with a Pearson correlation study. With an average age of 53 years, most of the
      carcinomas were type III (58%), followed by type II (30%) and at last type I
      (8%). Fifty-one of carcinomas were in stage IV at time of diagnosis. Ninety-five
      patients (60%) had remission. Five-year actuarial survival rate of all patients
      was 65.1%. There was a significant difference (P = 0.033) in the actuarial
      survival rate of staged IV patients treated with adjuvant chemotherapy.
      Undifferentiated nasopharyngeal carcinoma is the most frequent type in our
      geographic area. Chemotherapy improves survival rate, mainly in late stages.

PMID- 18830702
TI  - The dynamic transfer of 3H and 14C in mammals: a proposed generic model.
AB  - Associated with the present debate regarding the potential revival of nuclear
      energy there is an increased interest in assessing the radiological risk to the
      public and also the environment. Tritium and (14)C are key radionuclides of
      interest in many circumstances (e.g. heavy water reactors, waste storage and
      fusion reactors). Because the stable analogues of these two radionuclides are
      integral to most biological compounds, their modelling should follow general
      principles from life sciences. In this paper, a model of the dynamics of (14)C
      and (3)H in mammals is proposed on the basis of metabolic understanding and of,
      as far as possible, readily available data (e.g. for organ composition and
      metabolism). The model is described together with validation tests (without
      calibration) for a range of farm animals. Despite simplifications, the model
      tests are encouraging for a range of animal types and products (tissues and
      milk), and further improvements are suggested.

PMID- 18830704
TI  - Investigation of iron pools in cucumber roots by Mossbauer spectroscopy: direct
      evidence for the Strategy I iron uptake mechanism.
AB  - Distinct chemical species of iron were investigated by Mossbauer spectroscopy
      during iron uptake into cucumber roots grown in unbuffered nutrient solution with
      or without 57Fe-citrate. Mossbauer spectra of iron deficient roots supplied with
      10-500 microM 57Fe-citrate for 30-180 min and 24 h and iron-sufficient ones, were
      recorded. The roots were analysed for Fe concentration and Fe reductase activity.
      The Mossbauer parameters in the case of iron-sufficient roots revealed high-spin
      iron(III) components suggesting the presence of FeIII-carboxylate complexes,
      hydrous ferric oxides and sulfate-hydroxide containing species. No FeII was
      detected in these roots. However, iron-deficient roots supplied with 0.5 mM
      57FeIII-citrate for 30 min contained significant amount of FeII in a hexaaqua
      complex form. This is a direct evidence for the Strategy I iron uptake mechanism.
      Correlation was found between the decrease in Fe reductase activity and the ratio
      of FeII-FeIII components as the time of iron supply was increased. The data may
      refer to a higher iron reduction rate as compared to its uptake/reoxidation in
      the cytoplasm in accordance with the increased reduction rate in iron deficient
      Strategy I plants.

PMID- 18830703
TI  - Promoter proximal pausing on genes in metazoans.
AB  - The past two decades of research into transcriptional control of protein-encoding
      genes in eukaryotes have focused on regulatory mechanisms that act by controlling
      the recruitment of Pol II to a gene's promoter. Recent genome-wide analyses of
      the distribution of Pol II indicates that Pol II is concentrated in the promoter
      regions of thousands of genes in human and Drosophila cells. In many cases, Pol
      II may have initiated transcription but paused in the promoter proximal region.
      Hence, release of Pol II from the promoter region into the body of a gene is now
      recognized as a common rate-limiting step in the control of gene expression.
      Notably, most genes with paused Pol II are expressed indicating that the pause
      can be transient. What causes Pol II to concentrate in the promoter region and
      how it is released to transcribe a gene are the focus of this review.

PMID- 18830705
TI  - Towards engineering glucosinolates into non-cruciferous plants.
AB  - Glucosinolates are amino acid-derived secondary metabolites present in
      cruciferous plants. Glucosinolates and their hydrolysis products are involved in
      defence against insects and pathogens, but are also known for their
      characteristic flavor and their cancer-preventive and antibacterial properties.
      This wide range of bioactivities has prompted a desire to engineer glucosinolates
      into non-cruciferous plants. We report the one-step transfer of the last three
      steps of the benzylglucosinolate pathway (comprising the C-S lyase,
      glycosyltransferase and sulfotransferase) from Arabidopsis to tobacco. This was
      achieved using an expression construct consisting of a single 2A polycistronic
      open reading frame, which allowed the expression of the three coding-sequences
      from a single promoter. When compared to wildtype plants, transgenic tobacco
      lines showed increased ability to convert the intermediate
      phenylacetothiohydroxamate to benzylglucosinolate upon in vivo feeding. Enzymatic
      assays using plant extracts demonstrated that the individual activities required
      for this conversion were enhanced in the transgenic plants. The relatively high
      conversion by wildtype plants in feeding assays supports the hypothesis that the
      last part of the glucosinolate pathway was recruited from existing detoxification
      reactions. Immunoblots confirmed that individual proteins were being successfully
      produced from the 2A polycistronic open reading frame, albeit fusion proteins
      could also be detected. In summary, we transferred the last three steps of the
      benzylglucosinolate pathway to tobacco as a first step towards engineering
      glucosinolates into non-cruciferous plants.

PMID- 18830706
TI  - The promoter of ZmMRP-1, a maize transfer cell-specific transcriptional
      activator, is induced at solute exchange surfaces and responds to transport
      demands.
AB  - Transfer cells have specializations that facilitate the transport of solutes
      across plant exchange surfaces. ZmMRP-1 is a maize (Zea mays) endosperm transfer
      cell-specific transcriptional activator that plays a central role in the
      regulatory pathways controlling transfer cell differentiation and function. The
      present work investigates the signals controlling the expression of ZmMRP-1
      through the production of transgenic lines of maize, Arabidopsis, tobacco and
      barley containing ZmMRP-1promoter:GUS reporter constructs. The GUS signal
      predominantly appeared in regions of active transport between source and sink
      tissues, including nematode-induced feeding structures and at sites of vascular
      connection between developing organs and the main plant vasculature. In those
      cases, promoter induction was associated with the initial developmental stages of
      transport structures. Significantly, transfer cells also differentiated in these
      regions suggesting that, independent of species, location or morphological
      features, transfer cells might differentiate in a similar way under the influence
      of conserved induction signals. In planta and yeast experiments showed that the
      promoter activity is modulated by carbohydrates, glucose being the most effective
      inducer.

PMID- 18830707
TI  - Mycosporine-like amino acids (MAAs) profile of a rice-field cyanobacterium
      Anabaena doliolum as influenced by PAR and UVR.
AB  - The mycosporine-like amino acid (MAA) profile of a rice-field cyanobacterium,
      Anabaena doliolum, was studied under PAR and PAR + UVR conditions. The high
      performance liquid chromatographic analysis of water-soluble compounds reveals
      the biosynthesis of three MAAs, mycosporine-glycine (lambda (max) = 310 nm),
      porphyra-334 (lambda (max) = 334 nm) and shinorine (lambda (max) = 334 nm), with
      retention times of 4.1, 3.5 and 2.3 min, respectively. This is the first report
      for the occurrence of mycosporine-glycine and porphyra-334 in addition to
      shinorine in Anabaena strains studied so far. The results indicate that
      mycosporine-glycine (monosubstituted) acts as a precursor for the biosynthesis of
      the bisubstituted MAAs shinorine and porphyra-334. Mycosporine-glycine was under
      constitutive control while porphyra-334 and shinorine were induced by UV-B
      radiation, indicating the involvement of UV-regulated enzymes in the
      biotransformation of MAAs. It seems that A. doliolum is able to protect its cell
      machinery from UVR by synthesizing a complex set of MAAs and thus is able to
      survive successfully during the summer in its natural brightly lit habitats.

PMID- 18830708
TI  - Differential transcriptional regulation of banana sucrose phosphate synthase gene
      in response to ethylene, auxin, wounding, low temperature and different
      photoperiods during fruit ripening and functional analysis of banana SPS gene
      promoter.
AB  - Sucrose phosphate synthase (SPS) (EC 2.3.1.14) is the key regulatory component in
      sucrose formation in banana (Musa acuminata subgroup Cavendish, cv Giant
      governor) fruit during ripening. This report illustrates differential
      transcriptional responses of banana SPS gene following ethylene, auxin, wounding,
      low temperature and different photoperiods during ripening in banana fruit.
      Whereas ethylene strongly stimulated SPS transcript accumulation, auxin and cold
      treatment only marginally increased the abundance of SPS mRNA level, while
      wounding negatively regulated SPS gene expression. Conversely, SPS transcript
      level was distinctly increased by constant exposure to white light. Protein
      level, enzymatic activity of SPS and sucrose synthesis were substantially
      increased by ethylene and increased exposure to white light conditions as
      compared to other treatments. To further study the transcriptional regulation of
      SPS in banana fruit, the promoter region of SPS gene was cloned and some cis
      acting regulatory elements such as a reverse GCC-box ERE, two ARE motifs
      (TGTCTC), one LTRE (CCGAA), a GAGA-box (GAGA...) and a GATA-box LRE (GATAAG) were
      identified along with the TATA and CAAT-box. DNA-protein interaction studies
      using these cis-elements indicated a highly specific cis-trans interaction in the
      banana nuclear extract. Furthermore, we specifically studied the light responsive
      characteristics of GATA-box containing synthetic as well as native banana SPS
      promoter. Transient expression assays using banana SPS promoter have also
      indicated the functional importance of the SPS promoter in regulating gene
      expression. Together, these results provide insights into the transcriptional
      regulation of banana SPS gene in response to phytohormones and other
      environmental factors during fruit ripening.

PMID- 18830709
TI  - Blood pressure levels in childhood: probing the relative importance of birth
      weight and current size.
AB  - Several studies have reported data supporting the idea that an impaired
      intrauterine environment that deprives the fetus of optimal nutrient delivery
      results in the predisposition of the fetus to experience cardiovascular and
      metabolic dysfunction in later life. However, contradictory data still exist. Our
      purpose was to investigate the effects of both birth weight and weight gain on
      the risk for high blood pressure levels in 6- to 10-year-old children. This cross
      sectional study included 739 children divided into quartiles of birth weight. The
      mean values of both systolic and diastolic pressure were significantly different
      between quartiles of birth weight, with increasing blood pressure values as the
      birth weight decreased (P<0.001). Covariance analysis adjusting for gender,
      prematurity, and body mass index (BMI) showed that both systolic and diastolic
      pressure remained greater in the lowest than in the highest birth weight
      quartile. Separating those with low and normal birth weight demonstrated that the
      risk of childhood hypertension was significantly higher among children with low
      birth weight and current obesity (odds ratio [OR]: 5.0, confidence interval [CI]:
      3.3 to 16.1; P=0.023). The inverse association between birth weight and blood
      pressure levels appears to be programmed during fetal life, while weight gain
      during childhood adds to this risk.

PMID- 18830710
TI  - Preoperative cervical lymph node size evaluation in patients with malignant
      head/neck tumors: comparison between ultrasound and computer tomography.
AB  - PURPOSE: The spread of malignant lymph nodes due to malignancies of the head and
      neck is systematically observed. However, sentinel lymph nodes in the cervical
      region, such as in the axillary or supraclavicular regions, are not described.
      Therefore, precise preoperative lymph node screening of all neck compartments is
      required. MATERIALS AND METHODS: Forty-five patients with a primary malignant
      tumor in the head and neck area underwent lymph node staging of the head by means
      of both CT and ultrasound as a preoperative evaluation. The lymph nodes were
      classified on the origin of the level system proposed by Som et al. (174:837-844,
      2000), which is based on the recommendation of the American College of Radiology
      introduced in 1990. According to the manual measurement of World Health
      Organization and the Revised Response Evaluation Criteria in Solid Tumors, the
      longest transversal and longitudinal diameters were measured by ultrasound, while
      only the two longest transversal diameters were recorded by CT. The study was
      conducted by two independent observers. These results were compared with the
      histopathological results as references. RESULTS: Six hundred and twenty-four
      lymph nodes were detected, 64 of which were malignant. Most of the transformed
      lymph nodes were found in level IIa, II b and III. A more precise measurement was
      given using ultrasound. The correct positive rate of sonographically detected
      malignant lymph nodes was significantly higher compared to the CT reading.
      CONCLUSION: Cervical lymph node staging can be performed safely by ultrasound. It
      is a cheap, easy-to-handle and cost-effective diagnostic method. However, only
      the uppermost regions of the neck are accessible with a linear transducer.
      Despite this restriction, ultrasound is a reliable and valuable tool for
      screening lymph nodes in the case of a head or neck malignancy.

PMID- 18830711
TI  - Molecular characterization of the Aspergillus fumigatus NCS-1 homologue, NcsA.
AB  - Here, we characterize the Aspergillus fumigatus homologue ncsA Neuronal Calcium
      Sensor. We showed that ncsA is not an essential gene and ncsA growth was
      decreased in the presence of EGTA and SDS. Furthermore, the ncsA mutant is more
      resistant to calcium chloride. NcsA:mRFP localizes to the cytoplasm and its
      cellular localization is not affected by the cellular response to either calcium
      chloride or EGTA. The ncsA mutant strain is more sensitive to voriconazole,
      itraconazole, and amphotericin. Polar growth in the DeltancsA mutant was also
      considerably more affected by lovastatin than in the wild type strain. The
      Spitzenkorper can be visualized in both strains and although the vacuolar system
      does not seem to be very different, there is an increase in the staining
      intensity on the germling surface of the ncsA strain. NcsA promotes pmcA and pmcB
      expression and therefore there is a reduced expression of these ion pumps in the
      DeltancsA mutant background, and also of other genes involved in the response to
      calcium in A. fumigatus. The ncsA inactivation mutation is not causing loss of
      virulence in a low dose murine infection when compared to the corresponding wild
      type strain.

PMID- 18830712
TI  - Genome organisation and retrotransposon driven molecular evolution of the
      endosperm Hardness (Ha) locus in Triticum aestivum cv Glenlea.
AB  - Wheat endosperm texture is controlled primarily by a locus (Ha), which comprises
      Gsp-1, Pina and Pinb genes encoding the so-called grain softness protein,
      puroindoline-a and puroindoline-b, respectively. Pina and Pinb were detected only
      on the D-genome of hexaploid wheat and its diploid progenitors while Gsp-1 was on
      all three homoeologous loci. Hexaploid cultivar Glenlea has a hard phenotype due
      to a null Pina genotype (D-genome) but the sequence organization is not reported.
      This study aimed at understanding the evolution of homoeologous Ha loci.
      Sequencing of three BAC clones from cv Glenlea was performed and sequence
      analyses delimited the Ha loci which spanned 3,925, 5,330 and 31,607 bp in the A
      , B- and D-genomes, respectively. A solo LTR of Angela retroelement, downstream
      to Gsp-A1 and a fragment of Sabrina retroelement, downstream of Gsp-B1, were
      discovered. We propose that the insertion of these elements into the intergenic
      regions have driven the deletions of genomic segments harbouring Pina and Pinb
      genes in the A- and B-genomes of hexaploid wheat. Similarly, fragments of Romani
      and Vagabond retroelements were identified between truncated Pina and Pinb genes,
      indicating their role in the deletion of Pina in Glenlea, leading to its hard
      texture. Structural differences of the Ha locus region of the A-genome between
      two hexaploid wheat varieties namely Glenlea and Renan (CR626929), suggested the
      presence of more than one tetraploid ancestor in the origin of hexaploid wheat.

PMID- 18830713
TI  - A novel genetic locus for familial febrile seizures and epilepsy on chromosome
      3q26.2-q26.33.
AB  - Febrile seizures (FS) are common in children, and the incidence is 2-5% before
      the age of 5 years. A four-generation Chinese family with autosomal dominant
      febrile seizure and epilepsy was studied by genome-wide linkage analysis.
      Significant linkage was identified with markers on chromosome 3q26.2-26.33 with a
      maximum pairwise LOD score of >3.00. Fine mapping defined the new genetic locus
      within a 10.7-Mb region between markers D3S3656 and D3S1232. A maximum multipoint
      LOD score of 5.27 was detected at marker D3S1565. A previously reported CLCN2
      gene for epilepsy was excluded as the disease-causing gene in the family by
      mutational analysis of all exons and exon-intron boundaries of CLCN2 and by
      haplotype analysis. Mutation analysis of KCNMB2 and KCNMB3, which were two
      potassium-channel genes in this linkage region, did not reveal a disease causing
      mutation. Our results identified another novel locus on chromosome 3q26.2-26.33,
      and future studies of the candidate genes at the locus will identify a new gene
      for combined FS and idiopathic epilepsies.

PMID- 18830714
TI  - Genetic change following fire in populations of a seed-banking perennial plant.
AB  - Disturbances such as fire have the potential to remove genetic variation, but
      seed banks may counter this loss by restoring alleles through a reservoir effect.
      We used allozyme analysis to characterize genetic change in two populations of
      the perennial Hypericum cumulicola, an endemic of the fire-prone Florida scrub.
      We assessed genetic variation before and 1, 2, and 3 years after fire that killed
      nearly all aboveground plants. Populations increased in size following fire, with
      most seedlings likely recruited from a persistent seed bank. Four of five loci
      were variable. Most alleles were present in low frequencies, but our large sample
      sizes allowed detection of significant trends. Expected heterozygosity increased,
      and allele presence and allele frequencies showed marked shifts following fire.
      The post-fire seedling cohort contained new alleles to the study and one new
      allele to the species. Population differentiation between the two study sites did
      not change. Our study is the first to directly documents genetic changes
      following fire, a dominant ecological disturbance worldwide, and is also one of
      the few to consider shifts in a naturally recruiting post-disturbance seedling
      cohort. We demonstrate the potential of seed banks to restore genetic variation
      lost between disturbances. Our study demonstrates that rapid genetic change can
      occur with disturbance and that fire can have positive effects on the genetics of
      rare species.

PMID- 18830715
TI  - Atypical phenotype of type I Bartter syndrome accompanied by focal segmental
      glomerulosclerosis.
AB  - Type I Bartter syndrome (BS) is caused by mutations of the Na-K-2Cl cotransporter
      (NKCC2)-encoding SLC12A1 gene. The clinical phenotype of this severe form of BS
      is characterized by polyhydramnios, premature delivery, failure to thrive, and
      nephrocalcinosis, and the diagnosis is usually made during the antenatal-neonatal
      period. This report concerns a 29-year-old Japanese man with atypical type I BS
      due to a compound heterozygous mutation of the SLC12A1 gene. He was born after
      full-term pregnancy complicated by polyhydramnios. He first presented with
      asymptomatic proteinuria at the age of 20 years and was diagnosed with BS based
      on laboratory data. There were signs of moderate proteinuria, mild renal
      dysfunction and nephrocalcinosis. Renal biopsy showed focal segmental
      glomerulosclerosis (FSGS), and genetic testing revealed novel mutations of A555V
      and G809V in the SLC12A1 gene. The patient's sister showed the same clinical
      course, laboratory test abnormalities and gene mutations. Our patient had a type
      I BS with an atypical clinical course, which was diagnosed when he was 20 years
      old. Laboratory findings indicated phenotypic variability in this disease, and
      the presence of nephropathy suggested that FSGS might be one of the lesions
      causing end-stage renal failure in this disease.

PMID- 18830716
TI  - Methylated arginine derivatives in children and adolescents with chronic kidney
      disease.
AB  - Asymmetric dimethylarginine (ADMA), a methylated L: -arginine (Arg) derivative is
      associated with endothelial dysfunction, vasoconstriction, and hypertension in
      animals and humans. We examined the relationship between these derivatives,
      estimated glomerular filtration rate (eGFR), and awake (AW) and asleep (AS) blood
      pressure (BP) load in children and adolescents (n = 28) with stage 2-3 chronic
      kidney disease (CKD) and in matched intra-familial controls (n = 10). Plasma L: 
      Arg, ADMA, and symmetric dimethylarginine (SDMA) levels were measured by high
      performance liquid chromatography-tandem mass spectrometry. Subjects wore a 24-hr
      ambulatory BP monitor with BP load >95th percentile. ADMA, SDMA/ADMA ratio and
      SDMA were 38-200% higher in CKD patients while L: -Arg/ADMA and L: -Arg/SDMA
      ratios and the L: -Arg level were 11-64% lower. The eGFR explained 42-60% of L: 
      Arg/SDMA, SDMA/ADMA, and SDMA variability (n = 38). Using linear regression, SDMA
      and SDMA/ADMA separately explained 15-38% of AW and AS systolic (S) BP and
      diastolic (D) BP load variability (p < 0.001-0.022). Using multivariate stepwise
      regression with eGFR held constant, SDMA/ADMA was a significant independent
      variable for AW DBP load (p = 0.03). In conclusion, BP load and a
      disproportionate elevation of SDMA are seen in children and adolescents with
      stage 2-3 (mild-moderate) CKD. SDMA is a strong marker for reduced eGFR and
      serves as a moderate but significant indicator of 24-hr BP load variability.

PMID- 18830717
TI  - The risk factors of recurrent urinary tract infection in infants with normal
      urinary systems.
AB  - Urinary tract infection (UTI) frequently recurs and increases the risk of renal
      scarring even in infants with normal urinary tracts. Our study was aimed to find
      preventive measures for recurrent UTI in these infants. One-hundred ninety
      infants, who were diagnosed with their first febrile UTI and were proven to have
      normal urinary systems, were enrolled. We investigated the incidence of recurrent
      UTI during the following year and the following risk factors: gender, young age,
      phimosis, vaginal reflux, and acute pyelonephritis (APN) diagnosed by 99m
      technetium dimercaptosuccinic acid ((99m)Tc-DMSA)(+) scintigraphy. The incidence
      of recurrent UTI was 21.1%. The difference in recurrence rate according to gender
      was not significant. The recurrence rate in infants less than 6 months of age was
      25.8%, which was significantly higher than the 7.7% in older infants (P = 0.045).
      In male infants with persistent non-retractile prepuces, recurrent UTI developed
      in 34.0%, which was significantly higher than the 17.6% in male infants with
      retractile prepuces (P = 0.022). The presence of APN in male infants increased
      the likelihood of recurrent UTI when analyzed by multivariate logistic regression
      [odds ratio 4.6, 95% confidence interval (95% CI) 1.6-13.0, P = 0.003]. The
      presence of vaginal reflux and APN in female infants gave no significant
      difference to the incidence of recurrent UTI. In infants with normal urinary
      systems, age less than 6 months, non-retractile prepuces and APN in male infants,
      were the most important risk factors for recurrent UTIs. It is suggested that non
      retractile prepuces should be adequately treated to become retractile in young
      male infants with APN.

PMID- 18830718
TI  - Overall information needs of early-stage prostate cancer patients over a decade:
      highly variable and remarkably stable.
AB  - PURPOSE: To assess the stability of information needs of early-stage prostate
      cancer patients by comparing needs in the same location, at two time points,
      almost 10 years apart. METHOD: Two groups of patients were surveyed (first, 1996;
      second, 2005) to identify retrospectively their information needs in the
      diagnosis-to-treatment-decision time interval. Both sampling cohorts were men
      diagnosed in one location in Canada within the previous 2 years. Participants
      rated the importance of getting answers to each of 92 questions (organized in
      eight categories) using four options: essential, desired, no opinion, or avoid.
      For each essential and desired question, respondents also indicated the reason(s)
      they wanted the question addressed: to understand, decide, plan, or other.
      RESULTS: The two groups had similar response rates: 38 (68%) in 1996 and 130
      (70%) in 2005. They also had similar ages, marital status, or education. Both
      groups rated means of: 49 questions "essential" with wide ranges across
      respondents (12-90 vs 0-92 questions); 73 questions as "essential"/"desired"; and
      two questions to "avoid". At both times, every question was essential to some
      participants but only six (in 1996) and 12 (in 2005) questions were essential to
      over 80% of participants. In both groups, the most frequent reason for essential
      questions was for understanding (mean number of questions 34 vs 36), followed by
      decision making (means 13 vs 19), and then planning (means 10 vs 15).
      CONCLUSIONS: We have demonstrated reliably that, although many patients want a
      lot of information, the range in amount and in exact details varies considerably
      across individuals. Systematic patient education is needed, therefore, but it
      must be individualized.

PMID- 18830719
TI  - Does socioeconomic status in adolescence predict low back pain in adulthood? A
      repeated cross-sectional study of 4,771 Danish adolescents.
AB  - Social and economic disadvantage is associated with general poor physical health.
      This relationship has been recognised for centuries, but it is unknown whether
      socioeconomic factors have a specific influence on low back pain (LBP).
      Furthermore, it is unknown how social and economic disadvantages in youth affect
      adult health. Therefore, the specific objectives of this study are to explore (1)
      the cross-sectional association between socioeconomic status (SES) and LBP in
      adolescence and (2) the longitudinal association between SES in adolescence and
      LBP in early adulthood. A database containing LBP data from 4,771 twins was
      merged with their parents' social and economic data, available from Statistics
      Denmark. Low back pain data ['any low back pain' and 'persistent low back pain
      (more than 30 days)'] were collected in 1994, when the subjects were 12-18 years
      of age, and collected again eight years later. Socioeconomic data of the parents
      (education, income, social class and long-term illness, all for both mother and
      father) were collected in 1994. Logistic regression analyses were used to
      estimate the associations between each parameter of parental SES in adolescence
      and LBP at baseline as well as at follow-up. Finally, the influence of a variable
      combining the different socioeconomic parameters was established. All estimates
      were controlled for smoking, alcohol consumption and body mass index at baseline.
      In the logistic regression models, only three of the 32 estimates were
      statistically significant. When merging the socioeconomic variables into a
      combined score, the results indicated that a good social background had a
      protective effect against the persistent LBP, while there was no association with
      any LBP. However, the statistical significance of this effect was unclear. We
      found no or very weak indications of possible relationships between social
      factors in adolescence and LBP at baseline and at follow-up.

PMID- 18830720
TI  - Experience with an online prospective database on adolescent idiopathic
      scoliosis: development and implementation.
AB  - Considerable variability exists in the surgical treatment and outcomes of
      adolescent idiopathic scoliosis (AIS). This is due to the lack of evidence-based
      treatment guidelines and outcome measures. Although clinical trials have been
      extolled as the highest form of evidence for evaluating treatment efficacy, the
      disadvantage of cost, time, lack of feasibility, and ethical considerations
      indicate a need for a new paradigm for evidence based research in this spinal
      deformity. High quality clinical databases offer an alternative approach for
      evidence-based research in medicine. So, we developed and established Scolisoft,
      an international, multidimensional and relational database designed to be a
      repository of surgical cases for AIS, and an active vehicle for standardized
      surgical information in a format that would permit qualitative and quantitative
      research and analysis. Here, we describe and discuss the utility of Scolisoft as
      a new paradigm for evidence-based research on AIS. Scolisoft was developed using
      dot.net platform and SQL server from Microsoft. All data is deidentified to
      protect patient privacy. Scolisoft can be accessed at (www.scolisoft.org).
      Collection of high quality data on surgical cases of AIS is a priority and
      processes continue to improve the database quality. The database currently has 67
      registered users from 21 countries. To date, Scolisoft has 200 detailed surgical
      cases with pre, post, and follow up data. Scolisoft provides a structured process
      and practical information for surgeons to benchmark their treatment methods
      against other like treatments. Scolisoft is multifaceted and its use extends to
      education of health care providers in training, patients, ability to mine
      important data to stimulate research and quality improvement initiatives of
      healthcare organizations.

PMID- 18830721
TI  - Models of noncoupled dinuclear copper centers in azurin.
AB  - The successful modeling of metalloproteins is an important step in understanding
      their structure and function. Toward this goal, models of the noncoupled copper
      centers found in the enzymes peptidyl alpha-hydroxylating monooxygenase (PHM),
      dopamine beta-monooxygenase (DBM), and nitrite reductase (NiR) were designed into
      the small soluble protein azurin. The models are significant because they
      maintain the existing type 1 (T1) copper, electron transfer site of azurin while
      including the second designed type 2 (T2) copper center that mimics the T2
      catalytic sites in the target enzymes. UV-vis absorption and EPR spectroscopy
      data of the model sites are consistent with T2 centers and establish copper
      binding at the sites, thus modeling those found in PHM/DBM and NiR. Importantly
      the models' approximate 11-13 A separation between the T1 and T2 copper sites is
      comparable with the separations in the native systems. This, along with the power
      to tune the T1 site redox potential in azurin, allows for the future evaluation
      of relevant activity assays in these models.

PMID- 18830722
TI  - Intraprotein electron transfer in inducible nitric oxide synthase holoenzyme.
AB  - Intraprotein electron transfer (IET) from flavin mononucleotide (FMN) to heme is
      essential in NO synthesis by NO synthase (NOS). Our previous laser flash
      photolysis studies provided a direct determination of the kinetics of the FMN
      heme IET in a truncated two-domain construct (oxyFMN) of murine inducible NOS
      (iNOS), in which only the oxygenase and FMN domains along with the calmodulin
      (CaM) binding site are present (Feng et al. J. Am. Chem. Soc. 128, 3808-3811,
      2006). Here we report the kinetics of the IET in a human iNOS oxyFMN construct, a
      human iNOS holoenzyme, and a murine iNOS holoenzyme, using CO photolysis in
      comparative studies on partially reduced NOS and a NOS oxygenase construct that
      lacks the FMN domain. The IET rate constants for the human and murine iNOS
      holoenzymes are 34 +/- 5 and 35 +/- 3 s(-1), respectively, thereby providing a
      direct measurement of this IET between the catalytically significant redox
      couples of FMN and heme in the iNOS holoenzyme. These values are approximately an
      order of magnitude smaller than that in the corresponding iNOS oxyFMN construct,
      suggesting that in the holoenzyme the rate-limiting step in the IET is the
      conversion of the shielded electron-accepting (input) state to a new electron
      donating (output) state. The fact that there is no rapid IET component in the
      kinetic traces obtained with the iNOS holoenzyme implies that the enzyme remains
      mainly in the input state. The IET rate constant value for the iNOS holoenzyme is
      similar to that obtained for a CaM-bound neuronal NOS holoenzyme, suggesting that
      CaM activation effectively removes the inhibitory effect of the unique
      autoregulatory insert in neuronal NOS.

PMID- 18830723
TI  - Treatment of localized oral MALT lymphoma by rituximab: a case report.
AB  - INTRODUCTION: Extranodal marginal zone B cell lymphoma of mucosa-associated
      lymphoma tissue (MALT) among intraoral malignant lymphomas is very rare.
      Moreover, no case of oral MALT lymphoma treated with monoclonal antibody therapy
      has been reported. DISCUSSION: We describe a case of MALT lymphoma arising in an
      87-year-old Japanese woman under the buccal mucosa that was successfully treated
      with rituximab, a chimeric monoclonal antibody against the B cell-specific
      antigen CD20. Currently, 5 months after completing treatment, the patient is
      alive and has partial regression of the tumor.

PMID- 18830724
TI  - Assessment of Alzheimer's disease case-control associations using family-based
      methods.
AB  - The genetics of Alzheimer's disease (AD) is heterogeneous and remains only ill
      defined. We have recently created a freely available and continuously updated
      online database (AlzGene; http://www.alzgene.org ) for which we collect all
      published genetic association studies in AD and perform systematic meta-analyses
      on all polymorphisms with sufficient genotype data. In this study, we tested 27
      genes (ACE, BDNF, CH25H, CHRNB2, CST3, CTSD, DAPK1, GALP, hCG2039140, IL1B, LMNA,
      LOC439999, LOC651924, MAPT, MTHFR, MYH13, PCK1, PGBD1, PRNP, PSEN1, SORCS1,
      SORL1, TF, TFAM, TNK1, GWA_14q32.13, and GWA_7p15.2), all showing significant
      association with AD risk in the AlzGene meta-analyses, in a large collection of
      family-based samples comprised of 4,180 subjects from over 1,300 pedigrees.
      Overall, we observe significant association with risk for AD and polymorphisms in
      ACE, CHRNB2, TF, and an as yet uncharacterized locus on chromosome 7p15.2
      [rs1859849]. For all four loci, the association was observed with the same
      alleles as in the AlzGene meta-analyses. The convergence of case-control and
      family-based findings suggests that these loci currently represent the most
      promising AD gene candidates. Further fine-mapping and functional analyses are
      warranted to elucidate the potential biochemical mechanisms and epidemiological
      relevance of these genes.

PMID- 18830725
TI  - Risk factors for multidrug-resistant tuberculosis in a tuberculosis unit in
      Madrid, Spain.
AB  - The setting for this retrospective cohort study was a specialised tuberculosis
      unit in Madrid, Spain. The objective was to describe the risk factors for
      multidrug-resistant tuberculosis (MDR-TB). The medical records of all patients
      admitted to the unit were reviewed retrospectively to identify factors associated
      with multidrug resistance. Patients with positive culture for M. tuberculosis and
      with available drug-susceptibility tests were included. The variables assessed
      were age, gender, country of origin, homelessness, alcohol consumption,
      intravenous drug use, methadone substitution therapy, contact with a tuberculosis
      patient, sputum smear, site of disease, previous tuberculosis treatment, HIV
      infection, history of imprisonment, diabetes mellitus and chronic obstructive
      pulmonary disease. Thirty patients with MDR-TB and 666 patients with non-MDR-TB
      were included from the years 1997 to 2006. The only factors associated with MDR
      TB in multivariate analysis were previous tuberculosis treatment (OR: 3.44; 95%
      CI: 1.58-7.50; p = 0.003), age group 45-64 years (OR: 3.24; 95% CI: 1.34-7.81; p
      = 0.009) and alcohol abuse (OR: 0.12; 95% CI: 0.03 to 0.55; p = 0.003). In our
      study, patients who had had previous treatment for tuberculosis, who were 45-64
      years of age or who had no history of alcohol abuse were more likely to have MDR
      TB.

PMID- 18830726
TI  - An overview of the microbiology of acute ear, nose and throat infections
      requiring hospitalisation.
AB  - This study is the first to provide an extensive overview of the microbiology of
      acute ear, nose and throat infections requiring hospitalisation. All 2,028 cases
      of acute infections admitted between 1 January 2001 and 31 December 2006 were
      reviewed to assess the use of pre-admission antibiotics, microbiological results,
      antibiotic and surgical management and length of hospitalisation. Infections of
      the oropharynx accounted for the vast majority of admissions, followed by ear
      infections, and cutaneous neck abscesses. Peritonsillar abscess was the most
      frequent diagnosis, accounting for over one third of admissions (39.8%, 808 out
      of 2,028). Complete microbiological data were available for 1,430 cultures, and
      were analysed for trends with respect to diagnosis, age, gender and use of pre
      admission antibiotics. Forty-six percent (657 out of 1,430) of cultures yielded
      no growth or normal flora. This value increased to 77.0% (298 out of 387) in
      patients with pre-admission antibiotics. The distribution of microbiological
      isolates varied significantly between patients with and without pre-admission
      antibiotics, as well as with respect to age and gender. The most frequently
      isolated bacteria were Group A Streptococcus (13.7%, 196 out of 1,430),
      Fusobacterium necrophorum (13.6%, 195 out of 1,428) and Staphylococcus aureus
      (8.0%, 114 out of 1,430). Fusobacterium necrophorum was primarily isolated from
      cases of peritonsillar abscess (90.8%, 177 out of 195). This study suggests that
      F. necrophorum is a far more widespread pathogen in otorhinolaryngology than
      previously reported, and questions the value of routine culturing, as results
      rarely altered initial treatment. Further research on the microbiological
      variations with age and gender is recommended to better target culturing and
      treatment, and enhance our understanding of the pathogenesis of ear, nose and
      throat infections.

PMID- 18830727
TI  - Persistence of Streptococcus pneumoniae urinary antigen excretion after
      pneumococcal pneumonia.
AB  - The aim of this study was to determine the duration of Streptococcus pneumoniae
      antigen excretion in urine after pneumococcal pneumonia. Urinary antigen
      detection remained positive in nonconcentrated urine in 18 (52.9%) of the 34
      patients in the first month after pneumonia diagnosis. In 12 of these positive
      cases, the test was still positive in the second month, in six patients after 4
      months, and in two cases 6 months after the diagnosis of pneumonia. Using
      concentrated urine, antigenuria remained positive in all patients for at least 3
      months, with antigen detected in three cases more than one year later. We did not
      observe a relation between age, gender, immunosuppression, underlying diseases,
      pneumonia severity, positive blood culture, or X-ray presentation and longer-term
      antigenuria excretion. However, the small number of patients evaluated is a
      limitation for statistical analysis. In order to correctly analyse a positive
      urinary antigen test result in patients with pneumonia, it is necessary to know
      which patients have recently had a previous episode of pneumonia.

PMID- 18830728
TI  - Phenotypic and genetic characterisation of methicillin-resistant Staphylococcus
      aureus strains isolated from the university hospitals of Debrecen.
AB  - The purpose of this study was to characterise methicillin-resistant
      Staphylococcus aureus (MRSA) strains isolated in 2005 at the university hospitals
      of Debrecen, Hungary. Three hundred and thirty-nine MRSA strains were isolated
      from 102 patients at 18 different clinics. Their sensitivity to oxacillin and ten
      other antibiotics was determined. For genotypic analysis, phage typing and pulsed
      field gel electrophoresis (PFGE) was performed. The rate of MRSA strains
      increased to 7.2% in 2005, especially at the clinics of surgery, pulmonology and
      paediatrics. No vancomycin- or teicoplanin-resistant strains were found. The
      resistance to erythromycin, clindamycin and ciprofloxacin was nearly 100% and
      multi-resistance was very frequent. Fifty-eight percent of the isolates belonged
      to mixed phage types and 8% was non-typable. One PFGE clone contained 58.2% of
      all strains and two further major clones were found at a separately located
      clinical block, indicating intra-hospital spread. We can conclude that MRSA
      exhibits an increasing nosocomial problem also in Hungary.

PMID- 18830729
TI  - Characterization of extracellular esterase and lipase activities from five
      halophilic archaeal strains.
AB  - A total of 118 halophilic archaeal collection of strains were screened for
      lipolytic activity and 18 of them were found positive on Rhodamine agar plates.
      The selected five isolates were further characterized to determine their optimum
      esterase and lipase activities at various ranges of salt, temperature and pH. The
      esterase and lipase activities were determined by the hydrolysis of pNPB and
      pNPP, respectively. The maximum hydrolytic activities were found in the
      supernatants of the isolates grown at complex medium with 25% NaCl and 1% gum
      Arabic. The highest esterase activity was obtained at pH 8-8.5, temperature 60-65
      degrees C and NaCl 3-4.5 M. The same parameters for the highest lipase activities
      were found to be pH 8, temperature 45-65 degrees C and NaCl 3.5-4 M. These
      results indicate the presence of salt-dependent and temperature-tolerant
      lipolytic enzymes from halophilic archaeal strains. Kinetic parameters were
      determined according to Lineweaver-Burk plot. The KM and V (max) values were
      lower for pNPP hydrolysis than those for pNPB hydrolysis. The results point that
      the isolates have higher esterase activity comparing to lipase activity.

PMID- 18830730
TI  - The behavior of key enzymes of xylose metabolism on the xylitol production by
      Candida guilliermondii grown in hemicellulosic hydrolysate.
AB  - A variety of raw materials have been used in fermentation process. This study
      shows the use of rice straw hemicellulosic hydrolysate, as the only source of
      nutrient, to produce high added-value products. In the present work, the activity
      of the enzymes xylose reductase (XR); xylitol dehydrogenase (XD); and glucose-6
      phosphate dehydrogenase (G6PD) during cultivation of Candida guilliermondii on
      rice straw hemicellulosic hydrolysate was measured and correlated with xylitol
      production under different pH values (around 4.5 and 7.5) and initial xylose
      concentration (around 30 and 70 g l(-1)). Independent of the pH value and xylose
      concentration evaluated, the title of XD remained constant. On the other hand,
      the volumetric activity of G6PD increased whereas the level of XR decreased when
      the initial xylose concentration was increased from 30 to 70 g l(-1). The highest
      values of xylitol productivity (Q (P) approximately 0.40 g l(-1)) and yield
      factor (Y (P/S) approximately 0.60 g g(-1)) were reached at highest G6PD/XR ratio
      and lowest XR/XD ratio. These results suggest that NADPH concentrations influence
      the formation of xylitol more than the activity ratios of the enzymes XR and XD.
      Thus, an optimal rate between G6PD and XR must be reached in order to optimize
      the xylitol production.

PMID- 18830731
TI  - Validation of the WristOx 3100 oximeter for the diagnosis of sleep apnea/hypopnea
      syndrome.
AB  - OBJECTIVE: To evaluate the diagnostic accuracy of the Nonin WristOx 3100 and its
      software (nVision 5.0) in patients with suspicion of sleep apnea/hypopnea
      syndrome (SAHS). METHODS: All participants (168) had the oximetry and
      polysomnography simultaneously. The two recordings were interpreted blindly. The
      software calculated: adjusted O(2) desaturation index [ADI]-mean number of O(2)
      desaturation per hour of total recording analyzed time of > or = 2%, 3%, 4%, 5%,
      and 6% (ADI2, 3, 4, 5, and 6) and AT90-accumulated time at SO(2) < 90%. The ADI2,
      3, 4, 5, and 6 and the AT90 cutoff points that better discriminated between
      subjects with or without SAHS arose from the receiver operating characteristic
      curve analysis. The sensitivity (S), specificity (E), and positive and negative
      likelihood ratio (LR+, LR-) for the different thresholds for ADI were calculated.
      RESULTS: One hundred and fifty-four patients were included (119 men, mean age 51,
      median apnea/hypopnea index [AHI] 14, median body mass index [BMI] 28.3 kg/m(2)).
      The best cutoff points of ADI were: SAHS = AHI > or = 5: ADI2 > 19.3 (S 89%, E
      94%, LR+ 15.5 LR- 0.11); SAHS =AHI > or = 10: ADI3 > 10.5 (S 88%, E 94%, LR+ 15
      LR- 0.12); SAHS = AHI > or = 15: ADI3 > 13.4 (S 88%, E 90%, LR+ 8.9, LR- 0.14).
      AT90 had the lowest diagnosis accuracy. An ADI2 < or = 12.2 excluded SAHS (AHI >
      or = 5 and 10; S 100%, LR- 0) and ADI3 > 4.3 (AHI > or = 5 and 10) or 32 (AHI >
      or = 15) confirmed SAHS (E 100%). CONCLUSIONS: A negative oximetry defined as
      ADI2 < or = 12.2 excluded SAHS defined as AHI > or = 5 or 10 with a sensitivity
      and negative likelihood ratio of 100% and 0%, respectively. Furthermore, a
      positive oximetry defined as an ADI3 > 32 (SAHS = AHI > or = 15) had a
      specificity of 100% to confirm the pathology.

PMID- 18830732
TI  - LysoPtdOH enhances CXCL16 production stimulated by LPS from macrophages and
      regulates T cell migration.
AB  - As a transmembrane chemokine, CXCL16 has been detected in various tissues and
      organs under normal and pathological conditions, it also plays an important role
      in macrophages/dendritic cells (DC) and T cell interactions and trafficking
      during inflammation and immune responses. LysoPtdOH, a bioactive lipid mediator
      has been indicated to regulate DC and epithelial functions during wound healing
      and inflammation responses. However, the direct link of CXCL16 expression with
      lysoPtdOH has not been established. Using monocyte-derived macrophages/DC (MoDC),
      we investigated the roles of lysoPtdOH in CXCL16 production and cell surface
      presentation. We found that macrophages/MoDC constitutively express and secrete
      CXCL16, lysoPtdOH significantly enhanced CXCL16 protein production stimulated
      with lipopolysaccharide (LPS) by more than twofold, which was reflected by
      increased mRNA transcription by 64-fold. Production of CXCL16 increased by
      lysoPtdOH and LPS from macrophages was inhibited around 70% by Pertussis toxin
      (G(i/o) specific inhibitor), exoC3 (Rho specific inhibitor), and pyrrolidine
      dithiocarbamate (the NF-kappaB-dependent pathway inhibitor) separately. LysoPtdOH
      treatment increased macrophages' chemotactic activity to activated T cells. The
      soluble form of CXCL16 produced by macrophages/MoDC was functionally
      chemoattractive to T cells.

PMID- 18830733
TI  - [Abstracts of the German Pain Congress, 8-11 October 2008, Berlin, Germany].

PMID- 18830734
TI  - Endothelial nitric oxide synthase T-786C polymorphism in rheumatoid arthritis:
      association with extraarticular manifestations.
AB  - Several genetic factors were implicated in the pathogenesis of rheumatoid
      arthritis (RA). A case-control study was carried out to verify the associations
      of T-786C polymorphism in the promoter region of the endothelial nitric oxide
      synthase (eNOS) gene with RA. One hundred and five consecutive RA patients and
      100 healthy controls were genotyped. The distribution of the T-786C genotype and
      alleles did not differ significantly between RA patients and controls.
      Nevertheless, the frequency of extraarticular manifestations was significantly
      greater among the carriers of the C/C genotype than among carriers of the T/C and
      T/T genotypes (P = 0.022). The C/C genotype was significantly associated with
      extraarticular manifestations compared with the T/T and T/C genotypes taken
      together (OR = 4.9, 95% CI = 1.3-18.9). The C allele was significantly associated
      with extraarticular manifestations of RA (P(corr) = 0.032). The results suggested
      the existence of an association between the T-786C polymorphism of the eNOS gene
      and extraarticular manifestations of RA.

PMID- 18830735
TI  - Anal fistula: an unusual presentation of tuberculosis in a migrant health care
      professional.
AB  - We present a case of a young health care professional from the Indian
      subcontinent, who presented with a low anal fistula and underwent exploration,
      debridement and fistulotomy twice. The initial working diagnosis was Crohn's
      disease. However, Mycobacterium tuberculosis, fully sensitive to all first-line
      drugs was cultured from the specimens sent from the second surgical procedure. On
      initiation of anti-tubercular therapy the symptoms improved within 5 weeks. The
      origin of the patient, high index of suspicion for non-infectious reactivation of
      tuberculosis in migrant health care workers, importance of a proper history
      taking including previous exposure and diagnostic workup is stressed.

PMID- 18830736
TI  - Ablation of adrenal neoplasms.
AB  - Adrenal tumors represent a diverse group of neoplasms that include multiple
      etiologies, each with a different prognosis, malignant potential, and recommended
      treatment. Percutaneous techniques to treat adrenal neoplasms have been described
      including radiofrequency ablation, cryoablation, and chemical ablation. This
      article reviews the various adrenal neoplasms and the techniques of adrenal
      ablation.

PMID- 18830738
TI  - Managing water to protect fish: a review of California's Environmental Water
      Account, 2001-2005.
AB  - The Sacramento-San Joaquin Delta, the landward reach of the San Francisco
      Estuary, provides habitat for threatened delta smelt, endangered winter-run
      Chinook salmon, and other species of concern. It is also the location of huge
      freshwater diversion facilities that entrain large numbers of fish. Reducing the
      entrainment of listed fishes into these facilities has required curtailment of
      pumping, reducing the reliability of water deliveries. We reviewed the first 5
      years (2001-2005) of the Environmental Water Account (EWA), a program instituted
      to resolve conflicts between protecting listed fishes and providing a reliable
      water supply. The EWA provided fishery agencies with control over 0.2-0.4 km(3)
      of water to be used for fish protection at no cost to users of exported water,
      and fish agencies guaranteed no disruption of water supply for fish protection.
      The EWA was successful in reducing uncertainty in water supply; however, its
      contribution to the recovery of listed fishes was unclear. We estimated the
      effectiveness of the EWA to be modest, increasing the survival of winter-run
      Chinook salmon by 0-6% (dependent on prescreen mortality), adult delta smelt by 0
      1%, and juvenile delta smelt by 2-4%. Allocating EWA water for a single life
      stage of one species could provide larger gains in survival. An optimally
      allocated EWA of equal size to the median of the first 5 years could increase
      abundance of juvenile delta smelt up to 7% in the springs of dry years. If the
      EWA is to become a long-term program, estimates of efficacy should be refined. If
      the program is to be held accountable for quantitative increases in fish
      populations, it will be necessary to integrate scientific, possibly experimental,
      approaches.

PMID- 18830739
TI  - Valuation of spatial configurations and forest types in the southern appalachian
      highlands.
AB  - Site-specific estimates of the values of spatial configuration and forest
      composition are presented. Amenity values of forest patches are found to vary the
      most by urban and sprawling development patterns of specific areas and forest
      types. For example, smaller patches of deciduous forest are more highly valued in
      the urban and sprawling areas of Greensboro, North Carolina, whereas larger
      patches of deciduous forest are more highly valued in the urban and sprawling
      areas of Greenville, South Carolina. Within the Greenville and Greensboro areas,
      visible landscape complexity is highly valued for deciduous and evergreen forest
      patches, whereas lower visible landscape complexity, i.e., smoothly trimmed
      forest patch boundaries, is highly valued for mixed forest patches.

PMID- 18830740
TI  - A framework for assessing climate change impacts on water and watershed systems.
AB  - In this article we present a framework for assessing climate change impacts on
      water and watershed systems to support management decision-making. The framework
      addresses three issues complicating assessments of climate change impacts-
      linkages across spatial scales, linkages across temporal scales, and linkages
      across scientific and management disciplines. A major theme underlying the
      framework is that, due to current limitations in modeling capabilities, assessing
      and responding to climate change should be approached from the perspective of
      risk assessment and management rather than as a prediction problem. The framework
      is based generally on ecological risk assessment and similar approaches. A second
      theme underlying the framework is the need for close collaboration among climate
      scientists, scientists interested in assessing impacts, and resource managers and
      decision makers. A case study illustrating an application of the framework is
      also presented that provides a specific, practical example of how the framework
      was used to assess the impacts of climate change on water quality in a mid
      Atlantic, U.S., watershed.

PMID- 18830741
TI  - The decision analysis interview approach in the collaborative management of a
      large regulated water course.
AB  - There are always conflicting goals in the management of large water courses.
      However, by involving stakeholders actively in the planning and decision-making
      processes, it is possible to work together toward commonly acceptable solutions.
      In this article, we describe how we applied interactive multicriteria decision
      analysis (MCDA) in a collaborative process which aimed at an ecologically,
      socially, and economically sustainable water course regulation policy. The
      stakeholders' opinions about the alternative regulation schemes and the relative
      importance of their impacts were elicited with the HIPRE software. Altogether, 20
      personal interactive decision analysis interviews (DAIs) were carried out with
      the stakeholders. Our experience suggests that the DAIs can considerably improve
      the quality and efficiency of the collaborative planning process. By improving
      communication and understanding of the decision situation in the steering group,
      the approach helped to develop a consensus solution in a case having strong
      conflicts of interest. In order to gain the full benefits of the MCDA approach,
      interactive preference elicitation is vital. It is also essential to integrate
      the approach tightly into the planning and decision-making process. The project's
      home pages are available to the public at http://www.paijanne.hut.fi/.

PMID- 18830742
TI  - Transcatheter closure of total cavopulmonary connection lateral tunnel dehiscence
      and fenestration using a custom-made, self-expanding stent graft.

PMID- 18830743
TI  - Acute increase in hepatic arterial flow during TIPS identified by intravascular
      flow measurements.
AB  - The purpose of this study was to investigate alterations of hepatic arterial flow
      during transjugular intrahepatic portosystemic stent shunt (TIPS) applying
      intravascular Doppler sonography. This prospective monocenter study included 25
      patients with liver cirrhosis (alcohol induced [n = 19], chronic hepatitis
      associated [n = 3], primary biliary cirrhosis associated [n = 1], and cryptogenic
      [n = 2]) successfully treated with TIPS. All patients underwent intravascular
      hepatic arterial flow measurements during TIPS using an endoluminal flow sensor.
      The average arterial peak velocity (APV) and the maximum arterial peak velocity
      (MPV) were registered. Twenty-two patients (88%) showed increased APV, one
      patient (4%) showed unaffected APV, and two patients (8%) showed decreased APV
      after TIPS. The average portosystemic pressure gradient decreased significantly,
      from 22.0 +/- 5.1 mmHg before TIPS to 11.0 +/- 4.1 mmHg after TIPS (-50.0%; p <
      0.0001). The average APV increased significantly, from 41.9 +/- 17.8 cm/s before
      TIPS to 60.7 +/- 19.0 cm/s after TIPS (+44.9%; p < 0.0001). The average MPV
      increased significantly, from 90.8 +/- 31.7 cm/s before TIPS to 112.6 +/- 34.9
      cm/s after TIPS (+24.0%; p = 0.0002). These changes in perfusion set in within
      seconds after TIPS tract formation in all the patients with increased APV. We
      conclude that TIPS-induced portosystemic decompression leads to a significant
      increase in hepatic arterial flow. The changes occurred within seconds,
      suggesting a reflex-like mechanism.

PMID- 18830744
TI  - Poor sensitivity of the signify H. pylori test.

PMID- 18830745
TI  - Presence of pRI1: a small cryptic mobilizable plasmid isolated from Enterococcus
      faecium of human and animal origin.
AB  - This study focused on the molecular characterization of a small cryptic,
      mobilizable plasmid (6038 bp) sequenced from an E. faecium 9631160-1 of poultry
      origin. Sequence analysis of pRI1 revealed seven open reading frames. pRI1
      contained an IS 100% identical to ISEfa4. This insertion element disrupted a
      putative mobilization gene (mobA) which presented 99% similarity to the one
      described in plasmid pJS42 (NC_010291). pRI1 harbored a cluster of four coding
      sequences which exhibited a homology to those described in contig 658 (from
      nucleotide 8940 to nt 10515) of E. faecium DO. In addition, a rep almost
      identical to the repA from the pEFNP1 and pKQ10 plasmids from E. faecium was also
      identified. Presence of the pRI1 replication initiation gene (rep) was analyzed
      in a panel of 159 E. faecium isolates of human and animal origin from different
      European countries, of which 60 tested positive for the presence of pRI1-rep.
      Conjugation experiments verified transfer of the pRI1 together with conjugative
      plasmids harboring resistance to vancomycin and streptogramin. The presence of
      pRI1 in enterococcal isolates geographically separated and from different origin
      demonstrates the ability of enterococci to acquire and transfer mobile genetic
      elements, emphasizing the need for further studies to reveal the meaning and role
      that these cryptic plasmids play in nature.

PMID- 18830746
TI  - A comparison of gastrojejunal anastomoses with or without buttressing in a
      porcine model.
AB  - INTRODUCTION: The addition of staple-line reinforcements on circular anastomoses
      has not been well studied. We histologically and mechanically analyzed circular-
      stapled anastomoses with and without bioabsorbable staple-line reinforcement
      (SeamGuard, W. L. Gore & Associates, Flagstaff, AZ) in a porcine model. METHODS:
      Gastrojejunal anastomoses were constructed using a #25 EEA Proximate ILS (Ethicon
      Endo-Surgery, Cincinnati, OH) mechanical stapling device with and without
      Bioabsorbable SeamGuard (BSG). Gastrojejunal anastomoses were resected acutely
      and at 1 week, and burst-pressure testing and histological analysis were
      performed. Standardized grading systems for inflammation, collagen deposition,
      vascularity, and serosal inflammation were used to compare the two anastomosis
      types. RESULTS: Acute burst pressures were significantly higher with BSG than
      with staples alone (1.37 versus 0.39 psi, p=0.0075). Burst pressures at 1 week
      were significantly lower with BSG than with staples alone (2.24 versus 3.86 psi,
      p=0.0353); however, both readings were above normal physiologic intestinal
      pressures. There was no statistical difference in inflammation (13.4 versus 15.6,
      p=0.073), width of mucosa (3.2 mm versus 3.2 mm, p=0.974), adhesion formation (0
      versus 0.5, p=0.575), number of blood vessels (0.5 versus 1.0, p=0.056), or
      serosal inflammation (2.0 versus 1.0, p=0.27) between the stapled anastomoses and
      those buttressed with BSG. Stapled-only anastomoses had statistically more
      collagen (2.0 versus 1.0, p=0.005) than the anastomoses supported with BSG.
      CONCLUSIONS: The addition of BSG as a staple-line reinforcement acutely improves
      the burst strength of a circular anastomosis but not at 1 week. At 1 week, a
      decrease in collagen content with the BSG-buttressed stapled anastomosis was the
      only difference in the histologic parameters studied with no difference in
      vascularity, adhesions, or inflammation. The long-term effect of BSG on
      anastomotic strength or scarring is yet to be determined. The clinical
      implications may include decreased stricture formation and also decreased
      strength at anastomoses.

PMID- 18830747
TI  - Hormonal evaluation following laparoscopic treatment of type 2 diabetes mellitus
      patients with BMI 20-34.
AB  - BACKGROUND: A group of patients with type 2 diabetes mellitus (T2DM) and body
      mass index (BMI) 20-34 kg/m(2) were submitted to laparoscopic interposition of a
      segment of ileum into the proximal jejunum or into the proximal duodenum
      associated to a sleeve gastrectomy. The objective of this study is to evaluate
      the hormonal changes in the pre- and postoperative period. MATERIALS AND METHODS:
      Hormonal evaluation was done in 58 patients operated between April 2005 and July
      2006. Mean age was 51.4 years (40-66 years). Mean BMI was 28.2 (20-34.8) kg/m(2).
      All patients had had the diagnosis of T2DM for at least 3 years. Mean duration of
      T2DM was 9.6 years (3-22 years). Two techniques were performed, consisting of
      different combinations of ileal interposition (II) associated to a sleeve
      gastrectomy (SG). The following hormones were assayed in the pre- and
      postoperative period (mean 16 months) at the baseline and following specific food
      stimulation (30, 60, 120 min): glucogen-like protein 1 (GLP-1), glucose-dependent
      insulinotropic peptide (GIP), insulin, glucagon, C-peptide, amylin,
      cholecystokinin (CCK), pancreatic polypeptide (PPP), somatostatin, peptide YY
      (PYY), ghrelin, adiponectin, resistin, leptin, and interleukin-6 (IL-6). RESULTS:
      Thirty patients had II associated to sleeve gastrectomy (II-SG) and 28 had II
      with diverted sleeve gastrectomy (II-DSG). GLP1 exhibited an important rise
      following the two operations, especially after II-DSG (p < 0.001). GIP also
      exhibited an important rise, with both II-SG and II-DSG being equally effective
      (p < 0.001). Insulin and amylin showed a significant rise at 30 min. Glucagon
      decreased slightly. CCK measurements were very low after II-DSG. PPP was also
      slightly altered by the II-DSG. PYY showed an important increase with both
      operations (p < 0.001). Ghrelin showed a significant decrease following the two
      operations (p < 0.001). Somatostatin and IL-6 were not affected (p = 0.632). Both
      leptin and resistin blood levels decreased. Adiponectin showed a slight increase.
      Mean postoperative follow-up was 19.2 months. Both II-SG and II-DSG were
      effective in achieving adequate glycemic control (91.2%). CONCLUSIONS: There was
      a significant hormonal change following laparoscopic ileal interposition. These
      alterations may explain the promising good results associated to these operations
      for the treatment of T2DM in the nonmorbidly obese population.

PMID- 18830748
TI  - Esophageal dilation after laparoscopic adjustable gastric banding. Milone et al.
      Surg Endosc 2008;22:1482-1486.

PMID- 18830749
TI  - Management of endoscopic retrograde cholangiopancreatography: related duodenal
      perforations.
AB  - BACKGROUND: As the performance of upper gastrointestinal endoscopy, especially
      endoscopic retrograde cholangiopancreatography (ERCP), has increased since 1968,
      so has the incidence of duodenal perforations. The frequency of ERCP use varies
      among hospitals and depends on the availability of trained endoscopists,
      equipment, and facilities. METHODS: A retrospective review of ERCP-related
      perforations to the duodenum was conducted to identify their incidence, optimal
      management, and clinical outcome. Charts were reviewed for the following data:
      ERCP indication, clinical presentation, diagnostic methods, time to diagnosis and
      treatment, type of injury, management, length of hospital stay, and clinical
      outcome. RESULTS: From April 1999 to February 2008, 4,358 ERCP were performed, 15
      of which (0.34%) resulted in perforation to the duodenum. Only four of the
      perforations were discovered during ERCP, with another eight requiring computed
      tomography or abdominal radiography for diagnosis. Surgery was performed for 13
      of the patients (87%), and 2 patients died (15%). One patient was managed
      conservatively with a successful outcome. Nine patients underwent surgery within
      24 h after the ERCP, with only one patient undergoing surgery after 24 h. The
      overall mortality rate was 20% (3 of 15 patients). CONCLUSIONS: Clinical and
      radiographic features can be used to determine the surgical or conservative
      treatment of ERCP-related duodenal perforations, whereas patient age and
      intraoperative findings can determine the final outcome and morbidity or
      mortality. The interval between the perforation and the operation is of great
      significance. The mortality rate increases dramatically with late surgical
      management (>24 h). An algorithm for the selective management of ERCP-induced
      duodenal perforations is proposed.

PMID- 18830750
TI  - Laparoscopic ileal interposition associated to a diverted sleeve gastrectomy is
      an effective operation for the treatment of type 2 diabetes mellitus patients
      with BMI 21-29.
AB  - BACKGROUND: The objective of this study is to evaluate the clinical results of
      the laparoscopic interposition of a segment of ileum into the proximal duodenum
      associated to a sleeve gastrectomy (II-DSG) in order to treat patients with type
      2 diabetes mellitus (T2DM) and body mass index (BMI) 21-29 kg/m2. PATIENTS AND
      METHODS: The laparoscopic procedure was performed in 69 patients, 22 female and
      47 male. Mean age was 51 years (range 41-63 years). Mean BMI was 25.7 (21.8-29.2)
      kg/m2. All patients had the diagnosis of T2DM for at least 3 years and evidence
      of stable treatment with oral hypoglycemic agents and or insulin for at least 12
      months. Insulin therapy was used by 44% of the patients. Mean duration of T2DM
      was 11 years (range 3-18 years). Dyslipidemia was diagnosed in 72.5% and
      hypertension in 66.7%. Nephropathy was characterized in 29% of the patients,
      retinopathy in 26.1%, and neuropathy in 24.6%. RESULTS: Overall, 95.7% of the
      patients achieved adequate glycemic control (Hb(A1c) < 7%) without antidiabetic
      medication. Hb(A1c) below 6% was achieved by 65.2%. Mean postoperative follow-up
      was 21.7 months (range 7-42 months). Mean postoperative BMI was 21.8 kg/m2. There
      was no conversion to open surgery. Median hospital stay was 3.4 days (range 2-58
      days). Major postoperative complications were diagnosed in 7.3%. There was no
      mortality. Fasting glycemia decreased from a mean of 218 to 102 mg/dl,
      postprandial glycemia from 305 to 141 mg/dl, and homeostasis model assessment of
      insulin resistance (Homa-IR) from 5.2 to 0.77. All associated comorbidities and
      complications related to T2DM had significant improvement or control. Arterial
      hypertension was controlled in 91.3%. Macroalbuminuria was no longer observed.
      Microalbuminuria resolved in 87.5% of patients. Hypercholesterolemia was
      normalized in 95% and hypertriglyceridemia in 92% of patients. CONCLUSIONS:
      Laparoscopic II-DSG was an effective operation in controlling T2DM in a nonobese
      (BM < 30 kg/m2) population. Associated diseases and related complications were
      also improved. A longer follow-up period is needed.

PMID- 18830751
TI  - Optimal ergonomics for laparoscopic surgery in minimally invasive surgery suites:
      a review and guidelines.
AB  - BACKGROUND: With minimally invasive surgery (MIS), a man-machine environment was
      brought into the operating room, which created mental and physical challenges for
      the operating team. The science of ergonomics analyzes these challenges and
      formulates guidelines for creating a work environment that is safe and
      comfortable for its operators while effectiveness and efficiency of the process
      are maintained. This review aimed to formulate the ergonomic challenges related
      to monitor positioning in MIS. Background and guidelines are formulated for
      optimal ergonomic monitor positioning within the possibilities of the modern MIS
      suite, using multiple monitors suspended from the ceiling. METHODS: All evidence
      based experimental ergonomic studies conducted in the fields of laparoscopic
      surgery and applied ergonomics for other professions working with a display were
      identified by PubMed searches and selected for quality and applicability. Data
      from ergonomic studies were evaluated in terms of effectiveness and efficiency as
      well as comfort and safety aspects. Recommendations for individual monitor
      positioning are formulated to create a personal balance between these two
      ergonomic aspects. RESULTS: Misalignment in the eye-hand-target axis because of
      limited freedom in monitor positioning is recognized as an important ergonomic
      drawback during MIS. Realignment of the eye-hand-target axis improves personal
      values of comfort and safety as well as procedural values of effectiveness and
      efficiency. CONCLUSIONS: Monitor position is an important ergonomic factor during
      MIS. In the horizontal plain, the monitor should be straight in front of each
      person and aligned with the forearm-instrument motor axis to avoid axial rotation
      of the spine. In the sagittal plain, the monitor should be positioned lower than
      eye level to avoid neck extension.

PMID- 18830752
TI  - Minimally invasive congenital diaphragmatic hernia repair: a 7-year review of one
      institution's experience.
AB  - BACKGROUND: Minimally invasive surgery (MIS) has been described for the repair of
      congenital diaphragmatic hernias (CDH) in neonates, infants, and children. This
      report evaluates patient selection, operative technique, and clinical outcomes
      for MIS repair of CDHs from a single center's experience. METHODS: All cases of
      CDH at a tertiary care pediatric hospital with an initial attempt at MIS repair
      from January 2001 to December 2007 were reviewed. RESULTS: A total of 22 children
      underwent an initial attempt at MIS repair of their CDH (5 Morgagni and 17
      Bochdalek hernias). The children ranged in age from 1 day to 6 years (mean, 13.9
      +/- 23 months) and weighed 2.2 to 21 kg (mean, 7.4 +/- 5.50 kg) at the time of
      the operation. All five Morgagni hernias were managed successfully with
      laparoscopic primary repair. Six of the Bochdalek hernias were found in infants
      and children (age range, 6-71 months). All these were managed successfully with
      primary repair by an MIS approach (2 by laparoscopy and 4 by thoracoscopy). The
      remaining 11 Bochdalek hernias were found in neonates (age range, 1 day to 8
      weeks). Four of the Bochdalek hernias were right-sided. Nine of the Bochdalek
      hernias in neonates were repaired thoracoscopically. One neonate required
      conversion to laparotomy, and another underwent conversion to thoracotomy. Four
      of the neonates with Bochdalek hernias required a prosthetic patch. Two of the
      neonates also had significant associated congenital cardiac defects. Overall,
      there were two recurrences involving one 3-day-old who underwent a primary
      thoracoscopic repair and another 3-day-old who underwent a thoracoscopic patch
      repair. The follow-up period ranged from 5 months to 5 years. CONCLUSIONS:
      Morgagni hernias can be managed successfully by laparoscopy, whereas thoracoscopy
      is preferred for neonatal Bochdalek hernias. Either approach can be successful
      for infants and children with Bochdalek hernias. Additionally, patients with
      congenital cardiac defects and those requiring prosthetic patches can undergo a
      MIS CDH repair with a successful outcome.

PMID- 18830753
TI  - Hand-assisted laparoscopic partial nephrectomy after 60 cases: comparison with
      open partial nephrectomy.
AB  - BACKGROUND: Partial nephrectomy is the surgical standard of care for favorably
      located, small renal tumors. As the incidence of renal cell carcinoma (RCC) and
      detection of small kidney masses have increased over the past 20 years, minimally
      invasive management of these lesions has become more common. We report our single
      institution experience with hand-assisted laparoscopic partial nephrectomy
      (HALPN) compared with open partial nephrectomy (OPN). METHODS: Relevant outcome
      and demographic information was collected prospectively for HALPNs (N = 60) and
      retrospectively for OPNs (N = 40). A p-value of < 0.05 denotes statistical
      significance. RESULTS: Average tumor size (2.6 cm HALPN versus 2.6 cm OPN, p =
      0.97) was similar. Mean operative times were shorter for HALPN compared with OPN
      (161 versus 191 min, p = 0.027). HALPN was also associated with less blood loss
      (mean 120 cc versus 353 cc, p = 0.0003). Warm ischemia time was shorter for HALPN
      (mean 27.0 min versus 33.0 min, p = 0.035), as was hospital stay (mean 4.9 days
      versus 6.9 days, p = 0.007). Although four HALPN renal tumors required
      intraoperative margin re-excision (based on immediate gross evaluation by a
      pathologist), the final positive margin rate was 0%. A 5% final positive margin
      rate was observed in the OPN group. There were two conversions from HALPN to HAL
      radical nephrectomy and no conversions to an open technique. The HALPN minor
      complication rate was 18.3% versus 32.5% for OPN (p = 0.10). Complications
      included delayed bleeding (1, 2.5% OPN), urine leak (2, 5% OPN; 2, 3.3% HALPN),
      hypoxia, and nausea or fever lasting >3 days. Tumor pathology was as follows:
      80.7% and 80% RCC, 12.3% and 8% oncocytoma, and 7% and 12% angiomyolipoma, for
      HALPN and OPN, respectively in each case. CONCLUSIONS: HALPN is associated with
      diminished blood loss, operating time, warm ischemia time, positive margin rates,
      and length of stay compared with OPN. In our institution, HALPN is the standard
      approach for patients with small, surgically accessible renal tumors.

PMID- 18830754
TI  - Hydroxy-propyl-methyl-cellulose is a safe and effective lifting agent for
      endoscopic mucosal resection of large colorectal polyps.
AB  - BACKGROUND: Endoscopic mucosal resection (EMR) is today the treatment of choice
      for flat and sessile colorectal lesion, the only concern being completeness of
      resection. One of the major issues is the choice of the infiltrating substance to
      enable a long-lasting cushion under the lesion. The aim of this study was to
      prospectively evaluate safety and efficacy of hydroxy-propyl-methyl-cellulose
      (HPMC) injection for this purpose. PATIENTS: All flat and sessile lesions of the
      colon and rectum larger than 20 mm and considered suitable for EMR were included.
      In all cases 0.8% HPMC solution was injected through a 23G needle, in quantity
      according to the endoscopist's indication. Primary endpoints of the study were:
      (1) ability to perform en bloc resection of the lesions by using this new
      injection means, (2) complete resection rate, and (3) early and late complication
      rate. RESULTS: We resected 27 flat, sessile, or laterally spreading lesions up to
      60 mm (28 mm average). Mean dose of HPMC injected was 10.2 ml (range 8-40 ml).
      Median procedure time was 32 min (range 15-105 min). En bloc resection was
      achieved in up to 21 cases (78%). Histologically detected complete tumour removal
      was achieved in 23 lesions, whereas lateral margins could not be properly
      evaluated in 4 cases due to coagulation artefacts. No perforation was observed.
      Procedural spurting bleeding was managed by epinephrine injection in one case and
      clip application in the remaining. Two case of local recurrence of adenomatous
      tissue were observed at 3 and 12 months, and treated by EMR. No complication
      related to the use of HPMC was observed. CONCLUSIONS: Injection of HPMC for EMR
      resulted safe and effective, allowing en bloc resection in the majority of cases
      with a limited number of complications. Continued progress in the field will
      include more outcomes research and techniques simplification.

PMID- 18830755
TI  - Disturbances in the circadian pattern of activity and sleep after laparoscopic
      versus open abdominal surgery.
AB  - BACKGROUND: Studies on the circadian variation in bodily functions and sleep are
      important for understanding the pathophysiological processes in the postoperative
      period. We aimed to investigate changes in the circadian variation in activity
      after minimally invasive surgery (laparoscopic cholecystectomy, LC) and major
      abdominal surgery (MAS) and if these changes correlated with postoperative
      subjective recovery measures. METHODS: We examined 76 and 44 patients undergoing
      LC and MAS, respectively, for 4 days before and after surgery. Subjective
      recovery parameters were assessed by visual analogue scale (sleep quality,
      general well-being and pain) and fatigue was measured by a ten-point fatigue
      scale. The activity levels of the patients were monitored by actigraphy (a wrist
      worn device measuring patient activity). Measures of circadian activity level
      [interday stability (IS), intraday variability (IV) and the amplitude (AMP)] were
      derived after nonparametric analysis of activity data. RESULTS: IS was
      significantly reduced both after MAS (0.72 before surgery and 0.58 after surgery,
      p < 0.0001) and after LC (0.76 before surgery and 0.66 after surgery, p <
      0.0001). The IS dropped significantly more following MAS surgery compared with
      following LC surgery (p < 0.001). The fragmentation of the rhythm IV increased
      and the amplitude dropped significantly after both LC and MAS surgery. Subjective
      recovery parameters were worse after MAS when compared with LC, and correlated
      significantly to the circadian activity parameters (IS, IV and AMP). CONCLUSION:
      Severely disturbed circadian activity parameters was found after both LC and MAS
      with worse changes after MAS. Measures of circadian activity pattern analyses
      correlated significantly with postoperative subjective recovery parameters.

PMID- 18830756
TI  - Phase I/II trial of induction chemotherapy followed by concurrent
      chemoradiotherapy and surgery for locoregionally advanced pancreatic cancer.
AB  - BACKGROUND: We used a novel combination of induction chemotherapy with
      gemcitabine (GEM) and cisplatin (CDDP), followed by concurrent chemoradiotherapy
      (CCRT) with the same agents in patients with locoregionally advanced pancreatic
      cancer. Surgery or additional chemotherapy followed on the basis of response.
      METHODS: Patients with borderline resectable or locally advanced pancreatic
      cancer received induction weekly with GEM (1000 mg/m(2)) or CDDP (30 g/m(2)).
      Patients without progression of disease then underwent surgery or CCRT, including
      four cohorts of escalating GEM/CDDP doses combined with full-dose radiotherapy.
      After CCRT, patients deemed resectable underwent surgery; patients with disease
      that remained unresectable and that did not progress received additional GEM/CDDP
      for 2 months. RESULTS: A mean 76% of intended GEM dose and 75% of CDDP dose was
      delivered during induction (n = 26). There were three incidences of grade 4
      toxicity (fever or neutropenia). After induction, five patients progressed and
      one patient underwent resection. Eighteen patients received CCRT, and three
      patients underwent resection. After CCRT, disease of 10 patients progressed, and
      in 5 patients, it remained unresectable without progression, and the patient
      received additional GEM/CDDP. Dose-limiting toxicity was at dose level IV
      (thrombocytopenia). Median overall and disease-specific survival was 13 months.
      CONCLUSION: GEM/CDDP induction chemotherapy followed by CCRT is well tolerated
      and rendered the disease of 4 of 26 patients resectable in this study. The
      recommended phase II dose for GEM and CDDP in combination with full-dose
      radiotherapy (5040 cGy) is 300 mg/m(2) and 10 mg/m(2) weekly for 5 weeks. Median
      survival in this group was 13 months. This neoadjuvant combined modality approach
      is both feasible and active; further studies are warranted.

PMID- 18830757
TI  - Predictive value of expression and promoter hypermethylation of XAF1 in hepatitis
      B virus-associated hepatocellular carcinoma treated with transplantation.
AB  - BACKGROUND: Transcriptional regulation of the putative tumor suppressor gene X
      linked inhibitor of apoptosis protein-associated factor 1 (XAF1) by promoter
      methylation has been related to tumor progression in gastric and bladder cancer.
      The aim of this study was to investigate the methylation status and expression
      level of XAF1 in human hepatitis B virus (HBV)-associated hepatocellular
      carcinoma (HCC) treated with liver transplantation (LT), and to evaluate
      potential predictive value for tumor recurrence. METHODS: The expression level
      and methylation status of XAF1 in three liver cancer cell lines (SMMC-7721,
      HepG2, and Hep3B) and 65 cases of HBV-associated HCC following LT were analyzed
      by RT-PCR (RT, reverse-transcriptase), immunohistochemistry, and methylation
      specific polymerase chain reaction (PCR). RESULTS: XAF1 transcripts were not
      observed or present at low levels in liver cancer cell lines and were restored by
      treatment with demethylating agent 5-aza-2'-deoxycytidine (5-Aza-dC). In vivo,
      methylation status was associated with protein level of XAF1 (P < 0.001) and
      serum level of alpha-fetoprotein (AFP) (P = 0.009). The expression pattern of
      XAF1 was associated with portal vein tumor thrombi (PVTT), preoperative AFP
      level, tumor size, and recurrence. Multivariate analysis revealed that expression
      level of XAF1 was an independent factor for predicting recurrence-free survival
      [hazard ratio 0.237, 95% confidence interval (CI) 0.095-0.592, P = 0.002].
      However, no significant association was found between methylation status and the
      risk of tumor recurrence. CONCLUSION: Promoter hypermethylation is a critical,
      but not the sole, mechanism for gene silencing of XAF1 in HCC. Protein level of
      XAF1 may serve as a potential biomarker for tumor recurrence after LT.

PMID- 18830758
TI  - Ultrasound-assisted percutaneous trigger finger release: is it safe?
AB  - Trigger fingers can be treated by open or percutaneous division of the A1 pulley.
      The open approach allows for visualization of the pulley, the tendon, and the
      adjacent neurovascular bundles. The percutaneous trigger finger release (PTFR)
      lacks an incision and is thought to lead to a quicker recovery, but the safety
      and efficacy of this blind procedure are often questioned. Ultrasound imaging has
      recently been introduced as an adjunct for guiding the needle during percutaneous
      trigger finger release. This study was designed to evaluate the safety and
      efficacy of needle trigger finger release with added ultrasound imaging. Eighteen
      fresh cadaver A1 pulleys were divided percutaneously and then evaluated by
      converting to an open technique and examining the pulleys, the tendons, and the
      neurovascular bundles. This study's ultrasound images demonstrated repeated
      puncture of the tendon sheath and of the neurovascular bundle during PTFR. The
      subsequent dissection revealed three out of 18 tendons with visible lacerations
      and 15 out of 18 A1 pulleys with incomplete division. We concluded that
      ultrasound-guided PTFR can be complicated by flexor tendon lacerations, potential
      injury to neurovascular bundles, and incomplete division of the A1 pulleys. While
      the clinical significance of these findings is unclear to us, it does raise
      questions regarding the safety and efficacy of percutaneous trigger finger
      release, even when adding ultrasound guidance.

PMID- 18830759
TI  - Intersection of online social networking with medical professionalism: can
      medicine police the facebook boom?

PMID- 18830760
TI  - Self-neglect and resistance to intervention: ethical challenges for clinicians.

PMID- 18830761
TI  - Update in addiction medicine for the primary care clinician.

PMID- 18830762
TI  - The increasing number of clinical items addressed during the time of adult
      primary care visits.
AB  - BACKGROUND: Primary care physicians report that there is insufficient time to
      meet patients' needs during clinical visits, but visit time has increased over
      the past decade. OBJECTIVE: To determine whether the number of clinical items
      addressed during the primary care visit has increased, and if so, whether this
      has been associated with changes in visit length and the pace of clinical work.
      DESIGN: Analysis of non-hospital-based adult primary care visits from 1997 to
      2005, as reported in the National Ambulatory Medical Care Survey. PARTICIPANTS: A
      total of 46,431 adult primary care visits. MEASUREMENTS: We assessed changes over
      time for the total number of clinical items addressed per visit (including
      diagnoses, medications, tests ordered, and counseling), visit duration, and
      average available time per clinical item. In adjusted analyses we controlled for
      patient and physician characteristics. RESULTS: The number of clinical items
      addressed per visit increased from 5.4 to 7.1 from 1997 to 2005 (p < 0.001).
      Visit duration concurrently increased from 18.0 to 20.9 min (p < 0.001). The
      increase in the number of clinical items outpaced the increase in duration,
      resulting in a decrease in time per clinical item from 4.4 to 3.8 (p = 0.04).
      These changes occurred across patient age and payer status and were confirmed in
      adjusted analyses. CONCLUSIONS: The volume of work associated with primary care
      visits has increased to a greater extent than has visit duration, resulting in
      less available time to address individual items. These findings have important
      implications for reimbursing physician time and improving the quality of care.

PMID- 18830763
TI  - Patient sex does not modify ejection fraction as a predictor of death in heart
      failure: insights from the APPROACH cohort.
AB  - BACKGROUND: Normal and low ejection fraction (EF) heart failure patients appear
      to have similar outcomes. OBJECTIVE: The object of this study was to determine
      whether sex modifies the effects of left ventricular EF on prevalent heart
      failure mortality. DESIGN: Prospective cohort study. PATIENTS: Patients (n = 6,
      095) with a diagnosis of heart failure and a measure of EF undergoing cardiac
      catheterization in Alberta, Canada between April 1999 and December 2004; follow
      up continued through October 2005. MEASUREMENTS: All-cause mortality was assessed
      in analyses stratified by patient sex and EF (<or=50% vs. >50%). MAIN RESULTS:
      Overall, female heart failure patients were older, had more hypertension,
      valvular disease, less systolic impairment and coronary artery disease. Baseline
      medication use was similar in the four sex-EF groups. Low EF heart failure
      mortality over 6.5 years was slightly higher but was not significantly modified
      by patient sex. This relationship remained unchanged after adjustment for
      differences in baseline characteristics and process of care (women normal EF,
      reference group; men normal EF adjusted HR 1.1, 95% CI 0.9-1.3; women low EF
      adjusted HR 1.5, 95% CI 1.1-2.0; men low EF adjusted HR 1.6, 95% CI 1.2-2.1).
      CONCLUSIONS: Patient sex did not appear to modify the negative effects of low EF
      on long-term survival in this prospective study of prevalent heart failure. The
      small absolute difference in survival between low and normal EF heart failure
      highlights the need for further research into optimal therapy for the latter, a
      less well-understood condition.

PMID- 18830764
TI  - Numeracy and communication with patients: they are counting on us.
AB  - Patient-centered interactive communication between physicians and patients is
      recommended to improve the quality of medical care. Numerical concepts are
      important components of such exchanges and include arithmetic and use of
      percentages, as well as higher level tasks like estimation, probability, problem
      solving, and risk assessment--the basis of preventive medicine. Difficulty with
      numerical concepts may impede communication. The current evidence on prevalence,
      measurement, and outcomes related to numeracy is presented, along with a summary
      of best practices for communication of numerical information. This information is
      integrated into a hierarchical model of mathematical concepts and skills, which
      can guide clinicians toward numerical communication that is easier to use with
      patients.

PMID- 18830765
TI  - Pneumococcal vaccination in general internal medicine practice: current practice
      and future possibilities.
AB  - BACKGROUND: Pneumococcal vaccine (PPV) is recommended for adults >or=65 years and
      those with chronic illness, but there are potential advantages of universal
      vaccination of adults age 50-64 years. OBJECTIVE: To assess reported (1)
      recommendations and administration practices of general internists for PPV, (2)
      barriers to vaccination, and (3) willingness to expand vaccination to all adults
      >or=50 years. METHODS: National survey of general internists representative of
      the American College of Physicians. RESULTS: Response rate was 74% (N = 326).
      Although 99% reported giving PPV, less than 20% used a computerized database to
      identify eligible patients by age or diagnoses and only 6% recalled patients.
      Major barriers included acute problems taking precedence over preventive care
      (39%), difficulty determining vaccination history (30%), not thinking of it/not a
      priority (20%), and inadequate reimbursement for vaccine (19%). If ACIP expanded
      recommendations, 60% would definitely and 37% would probably institute this
      change. CONCLUSIONS: Most general internists reported giving PPV, but delivery
      was hindered by competing demands, lack of systems to identify patients needing
      vaccination, and reimbursement issues. Barriers might be decreased by a policy of
      universal vaccination of adults >or=50 years, and the majority of physicians
      reported they would follow such a recommendation if it were made.

PMID- 18830766
TI  - Publication guidelines for quality improvement studies in health care: evolution
      of the SQUIRE project.
AB  - In 2005 we published draft guidelines for reporting studies of quality
      improvement interventions as the initial step in a consensus process for
      development of a more definitive version. The current article contains the
      revised version, which we refer to as SQUIRE (Standards for QUality Improvement
      Reporting Excellence). We describe the consensus process, which included informal
      feedback, formal written commentaries, input from publication guideline
      developers, review of the literature on the epistemology of improvement and on
      methods for evaluating complex social programs, and a meeting of stakeholders for
      critical review of the guidelines' content and wording, followed by commentary on
      sequential versions from an expert consultant group. Finally, we examine major
      differences between SQUIRE and the initial draft, and consider limitations of and
      unresolved questions about SQUIRE; we also describe ancillary supporting
      documents and alternative versions under development, and plans for
      dissemination, testing, and further development of SQUIRE.

PMID- 18830767
TI  - The reflective writing class blog: using technology to promote reflection and
      professional development.
AB  - INTRODUCTION: The hidden (informal) curriculum is blamed for its negative effects
      on students' humanism and professional development. To combat this, educational
      initiatives employing mentored reflective practice, faculty role-modeling, and
      feedback have been advocated. AIM: Promote reflection on professional development
      using collaborative, web-based technology. SETTING: Four-week basic medicine
      clerkship rotation at an academic institution over a one-year period. PROGRAM
      DESCRIPTION: Students were asked to contribute two reflective postings to a class
      web log (blog) during their rotation. They were able to read each other's
      postings and leave feedback in a comment section. An instructor provided feedback
      on entries, aimed to stimulate further reflection. Students could choose
      anonymous names if desired. PROGRAM EVALUATION: Ninety-one students wrote 177
      posts. One-third of students left feedback comments. The majority of students
      enjoyed the activity and found the instructor's feedback helpful. Assessment of
      the posts revealed reflections on experience, heavily concerned with behavior and
      affect. A minority were not reflective. In some cases, the instructor's feedback
      stimulated additional reflection. Certain posts provided insight to the hidden
      curriculum. DISCUSSION: We have discovered that blogs can promote reflection,
      uncover elements of the hidden curriculum, and provide opportunities to promote
      professional development.

PMID- 18830768
TI  - Polyarteritis nodosa mimicking peripheral vascular disease.

PMID- 18830769
TI  - A multidisciplinary teamwork training program: the Triad for Optimal Patient
      Safety (TOPS) experience.
AB  - INTRODUCTION: Communication and teamwork failures are a common cause of adverse
      events. Residency programs, with a mandate to teach systems-based practice, are
      particularly challenged to address these important skills. AIM: To develop a
      multidisciplinary teamwork training program focused on teaching teamwork
      behaviors and communication skills. SETTING: Internal medicine residents,
      hospitalists, nurses, pharmacists, and all other staff on a designated inpatient
      medical unit at an academic medical center. PROGRAM DESCRIPTION: We developed a 4
      h teamwork training program as part of the Triad for Optimal Patient Safety
      (TOPS) project. Teaching strategies combined didactic presentation, facilitated
      discussion using a safety trigger video, and small-group scenario-based exercises
      to practice effective communication skills and team behaviors. Development,
      planning, implementation, delivery, and evaluation of TOPS Training was conducted
      by a multidisciplinary team. PROGRAM EVALUATION: We received 203 evaluations with
      a mean overall rating for the training of 4.49 +/- 0.79 on a 1-5 scale.
      Participants rated the multidisciplinary educational setting highly at 4.59 +/-
      0.68. DISCUSSION: We developed a multidisciplinary teamwork training program that
      was highly rated by all participating disciplines. The key was creating a shared
      forum to learn about and discuss interdisciplinary communication and teamwork.

PMID- 18830771
TI  - Addressing intimate partner violence with male patients: a review and
      introduction of pilot guidelines.
AB  - Intimate partner violence (IPV) is a common and devastating problem affecting the
      health of women, men, and children. Most health-care research focuses on the
      effects of IPV on women and children and addressing IPV with women in the health
      care setting. Less is known about addressing IPV with men in the health-care
      setting. This article reviews the challenges in interpreting research on IPV in
      men, its prevalence and health effects in men, and the arguments for addressing
      IPV with men in the health-care setting. It introduces pilot guidelines that are
      based on the existing literature and expert opinion.

PMID- 18830770
TI  - Impact of patient race on patient experiences of access and communication in HIV
      care.
AB  - BACKGROUND: Patient-centered care--including the domains of access and
      communication--is an important determinant of positive clinical outcomes.
      OBJECTIVE: To explore associations between race and HIV-infected patients'
      experiences of access and communication. DESIGN: This was a cross-sectional
      survey. PARTICIPANTS: Nine hundred and fifteen HIV-infected adults receiving care
      at 14 U.S. HIV clinics. MEASUREMENTS: Dependent variables included patients'
      reports of travel time to their HIV care site and waiting time to see their HIV
      provider (access) and ratings of their HIV providers on always listening,
      explaining, showing respect, and spending enough time with them (communication).
      We used multivariate logistic regression to estimate associations between patient
      race and dependent variables, and random effects models to estimate site-level
      contributions. RESULTS: Patients traveled a median 30 minutes (range 1-180) and
      waited a median 20 minutes (range 0-210) to see their provider. On average,
      blacks and Hispanics reported longer travel and wait times compared with whites.
      Adjusting for HIV care site attenuated this association. HIV care sites that
      provide services to a greater proportion of blacks and Hispanics may be more
      difficult to access for all patients. The majority of patients rated provider
      communication favorably. Compared to whites, blacks reported more positive
      experiences with provider communication. CONCLUSIONS: We observed racial
      disparities in patients' experience of access to care but not in patient-provider
      communication. Disparities were explained by poor access at minority-serving
      clinics. Efforts to make care more patient-centered for minority HIV-infected
      patients should focus more on improving access to HIV care in minority
      communities than on improving cross-cultural patient-provider interactions.

PMID- 18830772
TI  - Culture of endodermal stem/progenitor cells of the mouse tongue.
AB  - The tongue represents a very accessible source of tissue-specific epithelial stem
      cells of endodermal origin. However, little is known about the properties of
      these cells and the mechanisms regulating their proliferation and
      differentiation. Foxa2, an endodermal marker, is expressed throughout the tongue
      epithelium during embryonic development but becomes confined to a minority of
      basal cells and some taste bud sensory cells in the adult tongue. Using a
      previously described line of transgenic mice in which enhanced green fluorescent
      protein (eGFP) is expressed under the control of a human keratin 5 promoter
      region (Krt5-eGFP), we have isolated a subpopulation of cells in the basal
      epithelial layer of the mouse tongue with a high efficiency of generating
      holoclones of undifferentiated cells in culture with a feeder layer. Krt5-GFP(hi)
      cells can both self renew and give rise to differentiated stratified keratinized
      epithelial cells when cultured on an air-liquid interface.

PMID- 18830773
TI  - Establishment and characterization of porcine aortic endothelial cell cultures
      with prolonged replicative lifespan by a non-enzymatic method.
AB  - The aim of this work was the establishment and characterization of porcine aortic
      endothelial cell cultures with prolonged lifespan. Endothelial cells where
      isolated from porcine thoracic aorta and established in primary culture; after
      sub cultivation, the cells showed typical morphology of endothelial phenotype
      with cobblestone appearance and growth in monolayer; they were positive against
      anti-CD31 and anti-CD54 immunostaining and Ac-LDL-Dil uptake. The cells were able
      to migrate in culture and showed a normal growth curve. The phenotype of our in
      vitro model of endothelial cells was stable through subcultivation; so, it should
      be a valuable tool for diverse studies of the endothelial response against
      physiological and pathological stimulus, particularly it could be useful to study
      interactions of endothelium with pathogenic bacteria causing diseases in pigs, as
      they are difficult to study in vivo.

PMID- 18830774
TI  - The effects of unsaturated fatty acids on lipid metabolism in HepG2 cells.
AB  - We investigated the effects of stearic acid (saturated), oleic acid
      (monounsaturated), linoleic acid (n-6 polyunsaturated), and alpha-linolenic acid
      (n-3 polyunsaturated) on lipid metabolism in a hepatocyte-derived cell line,
      HepG2. HepG2 cells were cultured in medium supplemented with either stearic acid
      (0.1% w/v), oleic acid (0.1% v/v), linoleic acid (0.1% v/v), or alpha-linolenic
      acid (0.1% v/v). After 24 h, expression of lipid metabolism-associated genes was
      evaluated by real-time PCR. Alpha-linolenic acid showed a suppressive effect on
      the hepatic fatty acid de novo synthesis and fatty acid oxidation pathways, while
      linoleic acid also showed a tendency to suppress these pathways although the
      effect was weaker. Moreover, alpha-linolenic acid enhanced the expression of
      enzymes associated with reactive oxygen species (ROS) elimination. In contrast,
      oleic acid tended to promote fatty acid synthesis and oxidation. In conclusion,
      alpha-linolenic acid and linoleic acid may be expected to ameliorate hepatic
      steatosis by downregulating fatty acid de novo synthesis and fatty acid
      oxidation, and by upregulating ROS elimination enzymes. Oleic acid had no
      distinct effects for improving steatosis or oxidative stress.

PMID- 18830775
TI  - Attempts at immortalization of crustacean primary cell cultures using human
      cancer genes.
AB  - Primary cell cultures from crustacea have been initiated since the 1960s, yet no
      permanent cell line is available. Primary cells have a limited proliferative
      capacity in culture due to cellular senescence, which is regulated by a group of
      dominant senescence genes. The aim of this research was to manipulate cell cycle
      regulation by transfecting Cherax quadricarinatus primary cells with oncogenes,
      in an effort to induce a permanent cell line. Human papillomaviruses (HPV) play a
      critical role in the formation of anogenital cancer. Research has demonstrated
      that the HPV-expressed E6 and E7 proteins function concomitantly to disrupt the
      p53 and retinoblastoma (Rb) tumor suppressor genes, regulators of the cell-cycle
      checkpoints at the first gap (G(1)) phase. HPV E6 and E7 genes were transfected
      into the C. quadricarinatus cells by lipofection. Successful transfection was
      demonstrated by the presence of oncogene messenger RNA by reverse transciptase
      polymerase chain reaction. At day 150, transfected cells still remain viable,
      although cell proliferation was stagnant. It may be that while transfection of
      the oncogenes was successful, no proliferation of the C. quadricarinatus cells
      was evident due to a lack of telomere maintenance.

PMID- 18830776
TI  - Bariatric surgery in liver transplant patients: weighing the evidence.

PMID- 18830777
TI  - Results and complications after Swedish adjustable gastric banding in older
      patients.
AB  - BACKGROUND: Swedish adjustable gastric banding (SAGB) is an effective treatment
      for morbid obesity. The aim of this study was to assess the efficacy and safety
      of SAGB in older patients aged >or=50 years. METHODS: Between January 1996 and
      January 2006, 134 patients (102 women, 32 men) of 785 consecutive patients who
      underwent SAGB during the study period were aged >or=50 years. Two groups of
      patients were analyzed: Group 50 (n=107) patients aged 50-59 years and Group 60
      (n=27) patients aged 60-69 years. All data (demographic and morphologic data,
      operative data, and follow-up data) were prospectively collected in a
      computerized databank. RESULTS: One hundred thirty-four patients (17.1%) out of
      785 entered the study. Mean percentage of excess weight loss (%EWL) was 37.5 at 1
      year and 48.8 at 7 years, body mass index (BMI) fell from 43.3 to 33.1 at 7
      years. In the 134 patients, there were 65 patients with 121 complications (48.5%)
      and 69 patients with no complication (51.5%). The most common complications were
      esophagitis (27%), esophageal dilation (16%), port problems (11%), pouch dilation
      (11%), band leakage (9%), and band migration (7%). Overall, 46 patients (34%)
      needed a reoperation. In Group 50, mean %EWL was 38.4 at 1 year and 54.9 at 7
      years. BMI fell from 42.9 to 33.1 at 7 years. In the 107 patients, there were 55
      patients with 99 complications (51%) and a reoperation rate of 35.5%. In Group
      60, mean %EWL was 32.8 at 1 year and 41.2 at 7 years. BMI fell from 44.3 to 34 at
      7 years. In the 27 patients, there were ten patients with 22 complications (37%)
      and a reoperation rate of 29.6%. There was no mortality. CONCLUSIONS: At 7-year
      follow-up, for older patients, SAGB is an effective bariatric procedure for
      achieving weight loss. Nevertheless, based on the high complication and
      reoperation rate, a gastric band-specific patient selection will be necessary.

PMID- 18830778
TI  - Perforation of an adjustable gastric banding connecting tube into distal
      transverse colon with intra-luminal migration.
AB  - Laparoscopic adjustable gastric banding (LAGB) is one of the most common
      bariatric procedures performed in Europe and Australia. Major post-operative
      complications are limited but once they occur, prompt diagnosis and treatment are
      mandatory. LAGB complications are related either to the port and the connecting
      tube, such as infection or tubing disconnection and migration, or to the band,
      such as slippage, pouch dilatation, or intra-gastric migration. We report a case
      of intra-colonic migration of the connecting tube occurring 4 years after gastric
      banding placement in a patient otherwise asymptomatic.

PMID- 18830779
TI  - Single laparoscopic incision transabdominal (SLIT) surgery-adjustable gastric
      banding: a novel minimally invasive surgical approach.
AB  - Natural orifice transluminal endoscopic surgery (NOTES) has become an exciting
      area of surgical development. However, there are significant limitations to this
      surgical concept due to the lack of surgical expertise and appropriate flexible
      instrumentation. An alternative and competing technology to NOTES is single
      access surgery. We present a novel surgical technique for placement of an
      adjustable gastric band utilizing a single laparoscopic incision which was
      ultimately used for implanting the subcutaneous access port. This new technique
      is called single laparoscopic incision transabdominal (SLIT) surgery which
      describes an advanced laparoscopic bariatric operation that can be performed
      through a tiny slit. The operative time was 55 min. There were no intraoperative
      complications. The patient did well postoperatively and was discharged on
      postoperative day 1. There were no postoperative complications at 1-month follow
      up. Adjustable gastric banding performed through a single laparoscopic incision
      is technically feasible. The procedure was performed with mostly existing ports,
      laparoscopic instrumentations, and visualization platform. Advantages of SLIT
      surgery compared to conventional laparoscopic surgery will ultimately require
      further randomized clinical trials.

PMID- 18830780
TI  - Snack-eating patients experience lesser weight loss after Roux-en-Y gastric
      bypass surgery.
AB  - BACKGROUND: In bariatric surgery patients, weight loss and long-term weight
      maintenance are related to food intake and eating patterns. To improve the diet
      orientation in the bariatric surgery postoperative period, we assessed the
      postoperative eating patterns and related them to weight loss. METHODS: This was
      a transversal, analytical, and descriptive study that assessed body mass index
      (BMI) values and percentage of excess weight loss (%EWL) in patients who had
      undergone Roux-en-Y gastric bypass (RYGBP) surgery. The eating pattern and energy
      intake were investigated based on data collected through a 4-day food intake
      record. From these records, we assessed the number of daily meals, the quantity
      of food per meal, and calorie value of snacks between main meals. Based on these
      records, patients were classified under sweet-eating, snack-eating, or normal
      eating patterns. RESULTS: Seventy-five patients met our inclusion criteria. The
      normal-eating pattern group was the one with the greatest weight loss with an
      average %EWL of 71.4 +/- 21%, followed by the sweet-eating pattern with 69.9 +/-
      16.8%, and the snack-eating pattern with 56.4 +/- 16.7%. This difference was
      significant only between the first and the third group (p = 0.04). The snack
      eating patients had the highest caloric intake and highest number of daily meals
      (p < 0.01). CONCLUSION: Postoperative eating pattern influenced postbariatric
      surgery weight loss. In the present study, the snack-eating pattern was
      associated with the worst weight loss outcome, followed by the sweet-eating and
      normal-eating patterns. A screening and a differential approach to patients
      according to their eating patterns may lead to better results of weight loss.

PMID- 18830781
TI  - Cecal volvulus as a complication of gastric banding.
AB  - Surgery is an increasingly important management option for patients with obesity.
      Laparoscopic adjustable gastric banding is a procedure employed to treat morbid
      obesity refractory to medical therapy. It works by reducing the capacity of the
      stomach and promoting early satiety. We report the unusual case of a 33-year-old
      female who presented acutely 2 years following laparoscopic adjustable gastric
      banding with cecal volvulus and closed loop obstruction caused by displacement of
      the connecting tube.

PMID- 18830782
TI  - Inflammatory response measured by body temperature, C-reactive protein and white
      blood cell count 1, 3, and 5 days after laparotomic or laparoscopic gastric
      bypass surgery.
AB  - BACKGROUND: Morbid obesity is a chronic inflammatory condition due to the
      production of several cytokines from the adipose tissue. However, what happens
      with some of these parameters the first days after surgery is unknown. Therefore,
      the objective of the present study was to determine, through a prospective and
      descriptive study, the behavior of the C-reactive protein (CRP), the white blood
      cell count, and the body temperature prior to a gastric bypass and for 5 days
      afterwards. METHODS: A total of 156 patients with morbid obesity were included in
      this prospective study. There were 120 women and 36 men, with a mean age of 41
      years and a body mass index of 43 kg/m(2). They were submitted either to a
      laparotomic resectional gastric bypass or to a laparoscopic gastric bypass. Body
      temperature was measured every 8 h during 5 days. CPR and white blood cells were
      measured at the first, third, and fifth day after surgery. RESULTS: All patients
      had a normal postoperative course. Body temperature showed no change. White blood
      cells increased significantly at the first and third day after surgery but
      normalized by the fifth day. However, the third day after surgery, laparotomic
      gastric bypass patients showed a significantly greater increase in the total
      white blood cell count as well as in segmented neutrophil cells compared to
      laparoscopic surgery patients. CRP exhibited a similar increase and was more
      pronounced after a laparotomic approach. CONCLUSION: During the 5 days after
      gastric bypass, a significant increase in white blood cells and CRP was observed.
      The increase was significantly greater after a laparotomic bypass compared to the
      laparoscopic approach.

PMID- 18830783
TI  - Laparoscopic staged adjustable gastric banding and liver resection in morbidly
      obese patient.
AB  - We report the case of a 34-year old morbidly obese female, with a history of
      polycystic ovarian syndrome and birth control pill therapy, who underwent
      laparoscopic gastric banding. On laparoscopic exploration, a 4-cm liver neoplasm
      that was missed by preoperative ultrasound was incidentally found. The
      intraoperative biopsy was suggestive for a benign lesion of hepatocellular origin
      but could not make the differential diagnosis between focal nodular hyperplasia
      and adenoma. The neoplasm had atypical features on postoperative magnetic
      resonance imaging and was suggestive of liver adenoma. Six months after
      laparoscopic gastric banding, the patient presented with a weight loss of 24 kg
      and consented to liver resection. A laparoscopic resection of liver segment 3 was
      performed. Atypical liver neoplasms are subject to potential degeneration,
      rupture, and bleeding; therefore, they should be treated surgically to allow
      final diagnosis and potential cure of the disease. In this case, a staged
      approach was effective in obtaining substantial weight loss and a lesser degree
      of liver steatosis to enable the performance of a laparoscopic liver resection.

PMID- 18830784
TI  - Characteristics and outcome of patients admitted to the ICU following bariatric
      surgery.
AB  - BACKGROUND: This study evaluates the characteristics and outcome of patients
      admitted to the ICU following bariatric surgery. METHODS: Descriptive study. A
      review of a prospectively collected database of our bariatric surgery procedures
      from 2003 until 2006 was performed. The study was performed in a tertiary level,
      mixed medical and surgical, adult ICU of a large referral hospital. RESULTS: Of
      the 265 patients undergoing bariatric surgery (mainly gastroplasties and Roux-en
      Y gastric bypasses), 22 (8%) were admitted to the ICU, of which 14 (64%) were on
      an elective basis and eight (36%) emergently. Hospital length of stay (LOS) for
      all patients was 4.5 days and ICU LOS was 12 days. Most elective admissions were
      standard procedure because of obstructive sleep apnea (OSA) or super obesity,
      with a median ICU stay of 1 day. Emergent admissions were mainly done after
      emergent surgery due to surgical complications and had a median ICU stay of 8
      days. Only two patients needed intensive care for more than 3 days. There were no
      deaths during ICU stay. CONCLUSIONS: The ICU admission rate in our report is 8%.
      This study showed that 32 ICU days are needed per 100 diverse bariatric
      procedures. Most patients are admitted to the ICU for only a few days and the
      majority of the admissions is planned.

PMID- 18830785
TI  - Understanding the life experiences of Brazilian women after bariatric surgery: a
      qualitative study.
AB  - BACKGROUND: The increase in bariatric surgeries has called into question the
      aspects that contribute to or impair the results. Psychosocial factors directly
      influence the results of the surgery, but a lot of controversy exists in relation
      to the degree of influence of these factors. We propose a qualitative
      investigation to understand the significance of the surgery for women and how
      these factors influence the outcomes. METHODS: This study is a clinical
      qualitative method, through the semi-directed interview with open-ended questions
      in an intentional sample, closed by saturation, with seven women operated in a
      period of 1.5-3 years, following the definition of emergent categories and
      qualitative content analysis. RESULTS: The experience of acceptance and social
      reinsertion is a motivating factor to keep up the challenge of weight loss;
      social discrimination is a risk factor leading to losing the stimulus to continue
      the process; the recuperation of self-esteem and personal identity is a factor
      that improves the quality of life and psychopathological symptoms;
      disillusionment is an important risk factor, linked principally to the
      experiences of failure. CONCLUSION: We observe the necessity of qualitative
      studies that serve the health team in the handling of these patients, aiming for
      a greater understanding of their psychological dynamics and of the meanings that
      weight loss has for them.

PMID- 18830786
TI  - Sleeve gastrectomy leads to Helicobacter pylori eradication.
AB  - BACKGROUND: The role of Helicobacter pylori (HP) in patients scheduled and
      undergoing laparoscopic sleeve gastrectomy (LSG) has not been previously
      evaluated. METHODS: Included were obese patients presenting to our institution
      for LSG over 24 months. All patients had presurgical HP breath test, and the
      symptomatic ones received triple therapy with symptom follow-up. Post surgery,
      all excluded stomachs were evaluated for HP, and those that were positive
      performed a second 13C-urea breath test (UBT) 3 months later. RESULTS: Forty
      patients underwent LSG. Male to female sex ratio was 1:3; mean age-42 years; mean
      weight-122 kg; and mean BMI of 43.4 kg/m2. Presurgical HP was positive in 15
      (37.5%) patients (11 symptomatic and four asymptomatic). Only these 11 patients
      were given HP eradication therapy and all experienced complete subsequent symptom
      resolution. HP was detected in 17 out of the 40 (42.5%) cases of excluded
      stomachs. All performed a 13C-UBT 3 months post operation and only three (17.6%)
      tested positive. CONCLUSIONS: HP infection is frequent in biopsies from patients
      with previous LSG and the majority of follow-up 13C-UBT were negative. In our
      small initial sample, we treated only symptomatic patients preoperatively.
      Routine screening for HP for all LSG patients and/or treatment for all positive
      ones would subject patients to expensive and unnecessary investigations. We
      propose that this stomach-reducing, pylorus-preserving surgery might even lead to
      HP eradication. The clinical implications of HP and this gastrectomy for a non
      neoplastic, non-peptic indication deserve further study.

PMID- 18830787
TI  - Decrease in serum protein carbonyl groups concentration and maintained
      hyperhomocysteinemia in patients undergoing bariatric surgery.
AB  - BACKGROUND: Human obesity is associated with oxidative stress but the factors
      contributing to the increase of reactive oxygen species (ROS) production remain
      unknown. We evaluated the association between serum homocysteine concentration,
      which may increase ROS production, and serum protein carbonyl groups
      concentration before and after bariatric surgery. METHODS: Serum protein carbonyl
      groups and serum homocysteine concentrations, as well as obesity markers, were
      compared in 18 obese patients before and 6 months after bariatric surgery. Ten
      healthy individuals with normal body mass index (BMI) served as controls.
      RESULTS: Before bariatric surgery, obese patients displayed approximately 50%
      higher serum protein carbonyl groups concentration than control subjects. After
      surgery, serum protein carbonyl groups concentration decreased and matched values
      observed in controls. Serum homocysteine concentration was also elevated in obese
      patients, but in contrast to protein carbonyl groups, did not change after
      surgery. The body weight, BMI, HOMA-IR, serum leptin, triacylglycerols, LDL/HLD
      cholesterol ratio, insulin, and glucose concentrations were higher in obese
      patients as compared to controls, and decreased after bariatric surgery.
      CONCLUSIONS: This study demonstrates that bariatric surgery has protective effect
      on oxidative protein damage and improves several laboratory parameters including
      serum lipid concentration and insulin resistance. However, bariatric surgery does
      not cause a decrease in serum homocysteine concentration, a risk factor for the
      development of cardiovascular diseases. Collectively, the results presented in
      this paper suggest that serum homocysteine concentration is not directly
      associated with oxidative stress in obese patients after bariatric surgery.

PMID- 18830788
TI  - Bariatric surgery, safety and type 2 diabetes.
AB  - Obesity and type 2 diabetes (T2D) represent major health concerns in the USA.
      Weight loss is the most important aspect in T2D management, as it reduces both
      morbidity and mortality. Available lifestyle, behavioral, and pharmacological
      strategies provide just mild to moderate weight loss. The greatest degree of T2D
      prevention or T2D amelioration in obese subjects has been reported in subjects
      who underwent bariatric surgery. In the current review, we will describe various
      types of bariatric surgery, related safety profiles, and their effect on T2D, as
      well as the potential mechanisms involved in the remission of T2D. Finally, we
      hereby examine whether bariatric surgery may be considered a treatment for T2D in
      pregnant women, children, adolescents and subjects at least 65 years old.

PMID- 18830789
TI  - Retinol and alpha-tocopherol in morbid obesity and nonalcoholic fatty liver
      disease.
AB  - BACKGROUND: We aimed to study serum retinol and alpha-tocopherol in a cohort of
      obese patients and their possible association with several obesity-related
      conditions, given that the former may be implicated in a diminished capacity of
      anti-inflammatory and antioxidant potential in obese patients. METHODS: Eighty
      patients with morbid obesity participated in the study. Many clinical and
      biochemical variables were measured including serum retinol, alpha-tocopherol,
      aspartate aminotransferase (AST) and alanine aminotransferase (ALT)
      concentrations. Fatty liver was detected by ultrasonography. RESULTS: Both serum
      retinol and alpha-tocopherol inversely correlated with body mass index (r = 
      0.334, P = 0.002 and r = -0.299, P = 0.007, respectively). Serum retinol
      inversely correlated with AST (r = -0.236, P = 0.036) and ALT (r = -0.241, P =
      0.032). Multivariate regression analyses confirmed these results after correcting
      for the effects of other variables. Eighty-five percent of patients had fatty
      liver. When restricting the analysis to them, multivariate regression identified
      male sex (beta = 0.451, P = 0.003), age (beta = -0.275, P = 0.039), and serum
      retinol concentrations (beta = -0.414, P = 0.005) as predictive variables on
      serum AST (R (2) = 0.230, F = 3.408, P = 0.009) and male sex (beta = 0.448, P =
      0.003), age (beta = -0.236, P = 0.046), insulin resistance determined by
      homeostasis model assessment (beta = 0.243, P = 0.050), and serum retinol
      concentrations (beta = -0.305, P = 0.022) as predictive variables on serum ALT (R
      (2) = 0.296, F = 5.817, P = 0.001). CONCLUSION: Serum retinol and alpha
      tocopherol concentrations are inversely associated with body mass index in morbid
      obesity, and serum retinol is also inversely associated with serum concentrations
      of transaminases in those patients with nonalcoholic fatty liver disease.

PMID- 18830790
TI  - Small bowel obstruction and internal hernias during pregnancy after gastric
      bypass surgery.
AB  - Small bowel obstruction (SBO) is a recognized complication of Roux-en-Y gastric
      bypass (RYGB) surgery. Internal hernia (IH) a potential problem associated with
      RYGB, can have severe consequences if not diagnosed. We present two cases of SBO
      due to IH during pregnancy after laparoscopic RYGB (LRYGB). Both patients
      underwent an antecolic, antegastric LRYGB. In both patients a Petersen's type IH
      was found. We reviewed the cases reported in the literature of SBO during
      pregnancy after RYGB. IH should always be ruled out in pregnant patients with
      previous RYGB and abdominal pain. Prompt surgical intervention is mandatory for a
      good outcome.

PMID- 18830791
TI  - Etiology of ankle osteoarthritis.
AB  - The purpose of this study was to evaluate the distribution rate of etiologies
      leading to ankle arthritis and to quantify and compare the important clinical and
      radiologic variables among these etiologic groups. We evaluated data from 390
      patients (406 ankles) who consulted our center because of painful end-stage ankle
      osteoarthritis (OA) by using medical history, physical examination, and
      radiography. Posttraumatic ankle OA was seen in 78% of the cases (n = 318),
      secondary arthritis in 13% (n = 52), and primary OA in 9% (n = 36). The average
      American Orthopaedic Foot and Ankle Society (AOFAS) hindfoot score was 38 points
      (range, 0-74 points), range of motion was 22 degrees (range, 0 degrees-65
      degrees), and visual analog scale for pain was 6.8 (range, 2-10). Patients with
      posttraumatic end-stage ankle OA were younger than patients with primary OA. The
      average tibiotalar alignment was 88 degrees (range, 51 degrees-116 degrees) and
      did not differ between the etiologic groups. Our study showed trauma is the main
      cause of ankle OA and primary OA is rare. In the majority of patients with ankle
      OA the average tibiotalar alignment is varus regardless of the underlying
      etiology. LEVEL OF EVIDENCE: Level IV, prognostic study.

PMID- 18830792
TI  - Knee reconstruction with preservation of the meniscus in tibial giant cell tumor.
AB  - Giant cell tumor of bone sometimes is an aggressive benign skeletal tumor.
      Historically, curettage and bone grafting have a high recurrence with
      satisfactory function whereas wide resection has a reduced recurrence rate with
      compromise of limb function. Thus, maintaining joint function and achieving
      adequately wide resection introduces contradictory surgical goals. We developed a
      method for achieving both goals for giant cell tumors located in only one lateral
      plateau of the proximal tibia. We reconstructed 13 knees preserving the meniscus
      and reconstructing the tibial plateau with an iliac plate autograft after
      resection of a giant cell tumor involving one tibial plateau. Four patients had
      primary tumors and nine had recurrences after curettage. The minimum followup was
      5 years (mean, 9.1 years; range, 5-12.75 years). We used the system of Enneking
      et al. to evaluate function. One patient had recurrence and underwent prosthesis
      replacement. No patient experienced collapse, instability, or pain, and knee
      function was restored to near normal. The mean functional score was 95%. While
      resecting the tumor, the normal anatomic structures of the knee can be preserved
      or restored in many patients. This method can be used in selected patients to
      reconstruct the knee after resection of tumors involving one tibial plateau.
      LEVEL OF EVIDENCE: Level IV, therapeutic study. See the Guidelines for Authors
      for a complete description of levels of evidence.

PMID- 18830793
TI  - Effects of the balanced gap technique on femoral component rotation in TKA.
AB  - Femoral component rotation from a total knee prosthesis can be determined by
      either a measured resection technique or a balanced gap technique. With the
      balanced gap implantation technique, femoral component rotation can vary freely
      within the restrictions produced by soft tissue structures. Because internal
      rotation might cause patella problems, the effect of ligament releases on femoral
      component rotation in a prospective clinical study was studied. Femoral component
      rotation was measured intraoperatively with a tensor applied in flexion at 150 N
      in 87 knees. Great interpatient variability was found; femoral component
      rotation, reference from the posterior condyles, ranged from -4 degrees to 13
      degrees . There was no difference in femoral component rotation of knees with or
      without ligament releases in extension. However, knees with major medial release
      had less external femoral component rotation than knees with minor lateral
      releases. Preoperative alignment had no influence on femoral component rotation.
      The use of the balanced gap implantation technique theoretically will result in a
      balanced flexion gap, but the amount of femoral component rotation will be
      variable owing to patient variability and variation in ligament releases. LEVEL
      OF EVIDENCE: Level II, therapeutic study. See the Guidelines for Authors for a
      complete description of levels of evidence.

PMID- 18830794
TI  - Early experience with biodegradable implants in pediatric patients.
AB  - We retrospectively studied nine children and adolescents with congenital
      malformations, large reconstruction after tumor excision, fractures and
      osteotomies of the upper extremity, and hand trauma with bone and soft tissue
      defects treated by internal synthesis using a biocopolymer of L- and DL
      stereoisomers of lactic acid polymers and trimethylenecarbonate. A total of 52
      biodegradable implants were placed in bone. At a minimum followup of 7 months
      (mean, 17 months; range, 7-22 months), wound healing was uncomplicated; local or
      systemic inflammatory tissue reactions, foreign body reactions, and infections
      were not observed. Bone healing was complete. Six biodegradable screws broke
      during insertion because of inadequate drilling and tapping, and three
      biodegradable screws had to be replaced because of damage to the screw head
      during assembly with the screwdriver. Biodegradable copolymers of poly-L-lactic
      poly-DL-lactic acid and trimethylenecarbonate can be used safely and effectively
      for reconstruction and fixation of bone in children and adolescents. LEVEL OF
      EVIDENCE: Level IV, therapeutic study. See the Guidelines for Authors for a
      complete description of levels of evidence.

PMID- 18830795
TI  - The role of arthroscopy in evaluation of painful hip arthroplasty.
AB  - Unexplained pain after hip arthroplasty is frustrating for patients and surgeons.
      We describe the use of hip arthroscopy in management of the painful hip
      arthroplasty, critically evaluate the outcomes of these patients, and refine
      indications for hip arthroscopy in this setting. We retrospectively reviewed 14
      patients (16 hips) who underwent hip arthroscopy after joint replacement. One
      patient had suspected septic arthritis despite negative aspiration and one had
      known septic arthritis but was not a candidate for open arthrotomy; two had
      intraarticular migration of hardware. The remaining 10 patients (11 hips) had
      persistent pain despite negative diagnostic studies. The two patients (two hips)
      with infection were successfully treated with arthroscopic lavage and debridement
      plus intravenous antibiotics. Intraarticular metal fragments and a loose
      acetabular screw were successfully removed in two patients (three hips). Findings
      in the remaining 11 hips included a loose acetabular component (one); corrosion
      at the head-neck junction of a metal-on-metal articulation (one); soft tissue
      scar impingement at the head/cup interface (four); synovitis with associated scar
      tissue (four); and capsular scarring with adhesions (one). Arthroscopy
      represented a successful treatment or directly led to a successful treatment in
      12 of 16 hips. We observed no complications as a result of the arthroscopy.
      Arthroscopy may be of value in selected patients undergoing hip arthroplasty with
      unexplained pain after an inconclusive standard workup. LEVEL OF EVIDENCE: Level
      IV, therapeutic study. See the Guidelines for Authors for a complete description
      of levels of evidence.

PMID- 18830796
TI  - The 2008 Frank Stinchfield award: variation in postoperative pelvic tilt may
      confound the accuracy of hip navigation systems.
AB  - Most computer navigation systems used in total hip arthroplasty integrate
      preoperative pelvic tilt to calculate the anterior pelvic plane assuming tilt is
      constant; however, the consistency of pelvic tilt after THA has never been
      proven. Therefore, using a modern comprehensive gait analysis before and after
      arthroplasty we sought to compare (1) dynamic pelvic tilt changes and (2) pelvic
      flexion/extension range-of-motion changes. Twenty-one patients who underwent
      unilateral THA were prospectively studied. Quantitative pelvic tilt changes (in
      the sagittal plane) and pelvic range of flexion/extension motion relative to a
      laboratory coordinate system were compared using a computerized video motion
      system. Mean gait pelvic tilt was 13.9 masculine +/- 4.8 masculine (range, 1.73
      masculine-23.1 masculine) preoperatively, 12.5 masculine +/- 4.5 masculine
      (range, 1.4 masculine-18.7 masculine) 2 months postoperatively, and 10.5 degrees
      +/- 5.5 masculine (range, -2.36 masculine-19.2 masculine) 12 months
      postoperatively. A significant proportion (31%) of patients had more than a 5
      degrees difference between preoperative and 12-month postoperative measurements
      and the variability was spread over 20 degrees . Significant dynamic changes in
      pelvic tilt occurred after THA. While navigation clearly improves the anatomical
      position of the component during THA, the functional position of the component
      will not always be improved because of the significant change between
      preoperative and postoperative pelvic tilt.

PMID- 18830797
TI  - Activation tagging, an efficient tool for functional analysis of the rice genome.
AB  - Over the past 6 years, we have generated about 50,000 individual transgenic rice
      plants by an Agrobacterium-mediated transformation approach with the pER38
      activation tagging vector. The vector contains tandemly arranged double 35S
      enhancers next to the right border of T-DNA. Expression analysis by reverse
      transcription-PCR indicates that the activation efficiency is high if the genes
      are located within 7 kb of the inserted double 35S enhancers. Comparative field
      phenotyping of part of the activation tagging and enhancer trapping populations
      in two generations (6,000 and 6,400 lines, respectively, in the T(0) generation,
      and 36,000 and 32,000 lines, respectively, in the T(1) generation) identified
      about four hundred dominant mutants. Characterization of a dominant mutant with a
      large leaf angle (M107) suggests that this mutant phenotype is caused by enhanced
      expression of CYP724B1/D11. The activation tagging pool described in this paper
      is a valuable alternative tool for functional analysis of the rice genome.

PMID- 18830798
TI  - ACTIN DEPOLYMERIZING FACTOR9 controls development and gene expression in
      Arabidopsis.
AB  - Actin depolymerizing factors (ADF/cofilin) modulate the rate of actin filament
      turnover, networking cellular signals into cytoskeletal-dependent developmental
      pathways. Plant and animal genomes encode families of diverse ancient ADF
      isovariants. One weakly but ubiquitously expressed member of the Arabidopsis ADF
      gene family, ADF9, is moderately expressed in the shoot apical meristem (SAM).
      Mutant alleles adf9-1 and adf9-2 showed a 95% and 50% reduction in transcript
      levels, respectively. Compared to wild-type, mutant seedlings and plants were
      significantly smaller and adult mutant plants had decreased numbers of lateral
      branches and a reduced ability to form callus. The mutants flowered very early
      during long-day light cycles, but not during short days. adf9-1showed a several
      fold lower expression of FLOWERING LOCUS C (FLC), a master repressor of the
      transition to flowering, and increased expression of CONSTANS, an activator of
      flowering. Transgenic ADF9 expression complemented both developmental and gene
      expression phenotypes. FLC chromatin from adf9-1 plants contained reduced levels
      of histone H3 lysine 4 trimethylation and lysine 9 and 14 acetylation, as well as
      increased nucleosome occupancy consistent with a less active chromatin state. We
      propose that ADF9 networks both cytoplasmic and nuclear processes within the SAM
      to control multicellular development.

PMID- 18830799
TI  - The impact of physical activity on all-cause mortality in men and women after a
      cancer diagnosis.
AB  - OBJECTIVE: Existing information regarding the impact of physical activity after a
      cancer diagnosis on all-cause mortality is limited. We examined the association
      between different types of physical activity (domestic, walking, sports) and
      mortality in 293 participants (65.5% women) with a cancer registration prior to
      the baseline assessment. METHODS: Participants were drawn from the Scottish
      Health Surveys (1995, 1998, 2003) that were linked to a national database of
      cancer registrations and deaths. The main outcome was all-cause mortality during
      a mean follow-up period of 5.9 +/- 3.2 years. Cox proportional hazards models
      were used to estimate the risk of all-cause mortality by levels of physical
      activity. RESULTS: There were 78 deaths during follow-up. The lowest risks for
      all-cause mortality were seen in sports activity groups [multivariable-adjusted
      hazard ratio (HR) for any compared with groups of no sports: 0.47, 95% CI 0.23
      0.96, p = 0.039] although light and moderate activity such as domestic activity
      (HR = 1.04, 0.60-1.80) and regular walking (HR = 0.95, 0.57-1.56) did not confer
      protection. CONCLUSION: Participation in an average of more than three sessions
      of vigorous exercise per week for at least 20 min/session was associated with the
      lowest risks of all-cause mortality following a cancer diagnosis. Vigorous
      physical activity could therefore be a more important determinant of survival
      than duration or total volume of exercise in cancer survivors.

PMID- 18830800
TI  - Spatial variation in soil carbon in the organic layer of managed boreal forest
      soil--implications for sampling design.
AB  - We studied within-site spatial variation of the carbon stock in the organic layer
      of boreal forest soil. A total of 1,006 soil samples were taken in ten forest
      stands (five Scots pine stands and five Norway spruce stands). Our results
      indicate that the spatial autocorrelation disappears at a distance of 75-225 cm.
      This spatial autocorrelation should be taken into account in the sampling design
      by locating the sampling points at adequate intervals. With a sample size of over
      20-30 samples per site, additional soil samples do not notably improve the
      precision of the site mean estimate. An adequate sample size is dependent on the
      purpose of sampling and on the site-specific soil variation. Our results on the
      dependence between sample size and precision of the mean estimates can be applied
      in designing efficient soil monitoring in boreal coniferous forests.

PMID- 18830801
TI  - Urban activity and mercury contamination in estuarine and marine sediments
      (Southern Brazil).
AB  - The distribution of mercury in sediments of the Patos Lagoon estuary and nearby
      coastal marine deposits has been investigated for the period 1998-2008. Polluted
      urban soils and coastal reclamation fills are the principal sources of high
      mercury concentrations for shallow estuarine sediments. The shallow sediments
      that form near the urban area enter the navigation canal and are transported into
      the ocean. The mercury concentration in sediments of the navigation canal has
      considerably increased since 2004, due to intense reconstruction activity in the
      urban area. Periodic dredging of the canal strengthens the preconditions for
      coastal marine sediment contamination by mercury. However, this does not occur
      because the resuspended dredged sediments are significantly diluted by natural
      suspended particulate matter.

PMID- 18830802
TI  - Natural Jordanian zeolite: removal of heavy metal ions from water samples using
      column and batch methods.
AB  - The adsorption behavior of natural Jordanian zeolites with respect to Cd(2 + ),
      Cu(2 + ), Pb(2 + ), and Zn(2 + ) was studied in order to consider its application
      to purity metal finishing drinking and waste water samples under different
      conditions such as zeolite particle size, ionic strength and initial metal ion
      concentration. In the present work, a new method was developed to remove the
      heavy metal by using a glass column as the one that used in column chromatography
      and to make a comparative between the batch experiment and column experiment by
      using natural Jordanian zeolite as adsorbent and some heavy metals as adsorbate.
      The column method was used using different metal ions concentrations ranged from
      5 to 20 mg/L with average particle size of zeolite ranged between 90 and 350 mum,
      and ionic strength ranged from 0.01 to 0.05. Atomic absorption spectrometry was
      used for analysis of these heavy metal ions, the results obtained in this study
      indicated that zeolitic tuff is an efficient ion exchanger for removing heavy
      metals, in particular the fine particle sizes of zeolite at pH 6, whereas, no
      clear effect of low ionic strength values is noticed on the removal process.
      Equilibrium modeling of the removal showed that the adsorption of Cd(2 + ), Cu(2
      + ), Pb(2 + ), and Zn(2 + ) were fitted to Langmuir, Freundlich and Dubinin
      Kaganer-Radushkevich (DKR). The sorption energy E determined in the DKR equation
      (9.129, 10.000, 10.541, and 11.180 kJ/mol for Zn(2 + ), Cu(2 + ), Cd(2 + ) and
      Pb(2 + ) respectively) which revealed the nature of the ion-exchange mechanism.

PMID- 18830803
TI  - Expression of anti-K99 scFv in transgenic rice tissues and its functional
      characterization.
AB  - As a first step towards manufacturing functional anti-K99 single chain variable
      antibody fragment (scFv) in a plant system to prevent colibacillosis in neonatal
      calves, we investigated the feasibility of producing these antibodies in rice
      plants. Two scFv constructs, with or without the endoplasmic reticulum (ER)
      targeting KDEL sequence, were introduced into rice for either ER-retention of the
      recombinant antibody or its secretion. In agreement with several other published
      reports, extremely low-levels of scFv were produced in rice plants transformed
      with the construct lacking the ER-targeting sequence. Constructs containing the
      KDEL sequence resulted in significantly higher levels of the antibody in rice
      leaves. Although scFv transcripts were found in all three rice tissues analyzed,
      scFv protein was detected only in the leaf and embryo tissues and not in the
      endosperm portion of the seed. Functionality of the rice-produced scFv was tested
      in two in vitro assays, i.e., inhibition of K99-induced horse red blood cell
      agglutination and inhibition of the attachment of enterotoxigenic Escherichia
      coli (ETEC) to calf enterocytes. Rice-scFv was found to be functionally
      equivalent to anti-K99 monoclonal antibody (mAb) in both the assays. The results
      obtained in this investigation provide valuable information and in combination
      with other studies of this kind, will be helpful in devising strategies to
      improve production of useful recombinant proteins in the seeds.

PMID- 18830804
TI  - Four novel Candida species in the Candida albicans/Lodderomyces elongisporus
      clade isolated from the gut of flower beetles.
AB  - Flower-visiting beetles belonging to three species of Cetoniidae were collected
      on three mountains near Beijing, China, and yeasts were isolated from the gut of
      the insects collected. Based on the 26S rDNA D1/D2 domain and internal
      transcribed spacer (ITS) region sequence analysis and phenotypic
      characterization, four novel anamorphic yeast species located in the Candida
      albicans/Lodderomyces elongisporus clade were identified from 18 of the strains
      isolated. The new species and type strains are designated as Candida blackwellae
      AS 2.3639(T) (=CBS 10843(T)), Candida jiufengensis AS 2.3688(T) (=CBS 10846(T)),
      Candida oxycetoniae AS 2.3656(T) (=CBS 10844(T)), and Candida pseudojiufengensis
      AS 2.3693(T) (=CBS 10847(T)). C. blackwellae sp. nov. was basal to the branch
      formed by C. albicans and C. dubliniensis with moderately strong bootstrap
      support. The closest relative of C. oxycetoniae was L. elongisporus. C.
      jiufengensis sp. nov. and C. pseudojiufengensis sp. nov. were closely related
      with each other and formed a branch in a subclade represented by C. parapsilosis
      and L. elongisporus.

PMID- 18830805
TI  - Artificial photoactive proteins.
AB  - Solar power is the most abundant source of renewable energy. In this respect, the
      goal of making photoactive proteins is to utilize this energy to generate an
      electron flow. Photosystems have provided the blueprint for making such systems,
      since they are capable of converting the energy of light into an electron flow
      using a series of redox cofactors. Protein tunes the redox potential of the
      cofactors and arranges them such that their distance and orientation are optimal
      for the creation of a stable charge separation. The aim of this review is to
      present an overview of the literature with regard to some elegant functional
      structures that protein designers have created by introducing cofactors and
      photoactivity into synthetic proteins.

PMID- 18830806
TI  - Temporal change in bimanual interkeypress intervals and self-reported symptoms
      during continuous typing.
AB  - INTRODUCTION: Continuous typing is likely to induce mental and/or muscular
      fatigue, which contributes to musculoskeletal discomfort. Our goals were to
      describe the temporal changes in symptoms and interkeypress intervals (IKIs) of
      each hand during continuous typing. The effects of demographic characteristics
      and time on the IKI were examined. METHODS: Twenty-four healthy and skilled
      typists volunteered to participate in this repeated-measurement study. All the
      subjects typed an English text for 90 min in the laboratory. The outcomes
      included self-reported pain and fatigue, average typing speed, accuracy rate,
      finger tapping speed, and IKIs as recorded by electronic activity monitoring
      software (VDTlog). The changes in self-reported symptoms, average typing speed
      and accuracy rate after 90 min of typing were compared with baseline data by
      paired testing. The effects of demographic characteristics and time on IKIs of
      both hands were explored by generalized estimate equation (GEE) analysis.
      RESULTS: The pain and fatigue ratings of the study subjects were significantly
      higher after 60 and 90 min of typing, but the average typing speed of every 30
      min remained similar. The most common complaints were associated with the eyes,
      upper back and wrists. The IKIs as recorded by VDTlog was associated with typing
      speed. Furthermore, GEE analysis showed that the IKI of the right hand was the
      shortest in the last 10 min throughout the experiment, while left-hand typing
      exhibited the longest IKI during the last 10 min of each 30-min typing session.
      CONCLUSION: Time has different effect on the temporal changes of IKI during
      continuous typing for the left and right hands. Right-hand IKI tends to be
      shorter by time, especially at the last 10 min of typing, while left-hand IKI
      prolongs as typing continues for 30 min. Perceived pain and fatigue is apparent
      after continuous typing, though no change in average typing speed is observed.

PMID- 18830807
TI  - Health behaviors of older Chinese adults living in New York City.
AB  - The dramatic increase in the number of older immigrants living in the U.S.
      presents new challenges to policy makers concerned with promoting healthy aging.
      To date, however, strikingly little is known regarding the health and health
      trajectories of older immigrants. This paper examines the prevalence and
      predictors of important health behaviors associated with chronic disease
      prevention, including current smoking status, physical activity, alcohol use, and
      body mass index (BMI). We analyzed data from the 2003 New York City Chinese
      Health Survey (NYC CHS), the largest probability-based sample of Chinese
      immigrants residing in two distinct communities. In-person interviews were
      conducted with 517 representative men and women aged 55-75. Logistic regression
      modeling was used to test the influence of demographic, socioeconomic status,
      acculturation, and health characteristics on selected health behaviors. Results
      revealed that having more education and better physical health status were
      associated with greater participation in physical activity. Gender-specific
      analyses indicated that the effect of selected predictors varied between the
      sexes. For example, among older Chinese women, acculturation was negatively
      associated with alcohol use. This study provides some of the first evidence on
      health behaviors of one of the fastest growing older immigrant groups in the U.S.
      Study results add to the emerging literature on the complex nature of immigrant
      health trajectories, and demonstrate that contrary to prior research, living a
      greater proportion of time in the U.S. can be associated with selected positive
      health behaviors. Further longitudinal studies are needed to help inform policy
      initiatives to encourage healthy aging among diverse older immigrant groups.

PMID- 18830808
TI  - On the spatial inequalities of institutional versus home births in Ghana: a
      multilevel analysis.
AB  - Spatial inequalities related to the choice of delivery care have not been studied
      systematically in Sub-Saharan Africa where maternal and perinatal health outcomes
      continue to worsen despite a range of safe motherhood interventions. Using
      retrospective data from the 1998 and 2003 Demographic and Health Surveys, this
      paper investigates the extent of changes in spatial inequalities associated with
      type of delivery care in Ghana with a focus on rural-urban differentials within
      and across the three ecological zones (Savannah, Forest and Coastal). More than
      one-half of births in Ghana continue to occur outside health institutions without
      any skilled obstetric care. While this is already known, we present evidence from
      multilevel analyses that there exist considerable and growing inequalities, with
      regard to birth settings between communities, within rural and urban areas and
      across the ecological zones. The results show evidence of poor and
      disproportionate use of institutional care at birth; the inequalities remained
      high and unchanged in both urban and rural communities within the Savannah zone
      and widening in urban communities of the Forest and Coastal zones. The key policy
      challenges in Ghana, therefore, include both increasing the uptake of
      institutional delivery care and ensuring equity in access to both public and
      private health institutions.

PMID- 18830809
TI  - Changes in maternal cigarette smoking among pregnant WIC participants in Rhode
      Island.
AB  - OBJECTIVES: To describe the relationship between the timing of entry into the
      Special Supplemental Nutrition Program for Women, Infants, and Children (WIC)
      among pregnant women in Rhode Island (RI) and changes in maternal cigarette
      smoking (MCS) during pregnancy. METHODS: MCS data gathered by WIC were analyzed
      for pregnant women who self-identified as smokers at the onset of pregnancy
      between the years 2001-2005. Bivariate and multivariate analyses were performed
      to examine the relationship between timing of WIC entry and both increased and
      decreased/quit MCS during pregnancy. RESULTS: Self-reports from smokers indicated
      that 9.5% quit smoking, 24.6% decreased MCS, 26.8% experienced no change, 33.5%
      increased MCS, and 5.6% attempted to quit MCS but failed during pregnancy. The
      adjusted odds ratio for smokers with 1st trimester WIC entry and increased MCS
      was 0.64 (95% CI 0.52, 0.79). Among smokers with 1st trimester PNC entry, the
      adjusted odds ratio for smokers with 1st trimester WIC entry and decreased/quit
      MCS was 1.51 (95% CI 1.17, 1.96). CONCLUSIONS: Early WIC entry appears to be
      associated with improvements in MCS. Participants who entered WIC in the first
      trimester of pregnancy were less likely to increase smoking during pregnancy, and
      if they also had first trimester prenatal care, were more likely to decrease/quit
      smoking compared to those who entered WIC later. Programs that increase the rates
      of first trimester WIC entry may contribute to lower rates of MCS in the WIC
      population.

PMID- 18830810
TI  - Effect of an educational program (PEGASE) on cardiovascular risk in
      hypercholesterolaemic patients.
AB  - BACKGROUND: Many studies have demonstrated a gap between guidelines for the
      prevention of cardiovascular disease (CVD) and their implementation in clinical
      practice. AIM: The PEGASE education program has been devised with an aim to
      improve the management of patients at high risk of CVD. METHODS: In a multicentre
      study carried out from 2001-2004 in France, 96 participating physicians were
      randomized into a "trained" group, which included 398 "educated" patients, and a
      "non-trained" group, which included 242 "non-educated" patients. Educated
      patients received six hospital-based educational sessions, four collective and
      two individual. Framingham score, smoking, lipid levels, glycaemia, blood
      pressure, dietary intake and drug compliance, as well as quality of life, were
      evaluated at baseline (M0) and 6 months (M6). The primary endpoint of the study
      was the efficacy of the PEGASE program in reducing global CVD risk in high-risk
      patients. RESULTS: The Framingham score was calculated for 473 patients. The
      Framingham score improved significantly at M6 vs M0 in the educated group (13.0
      +/- 8.21 vs 13.6 +/- 8.48, d = -0.658, p = 0.016), but not in the non-educated
      group (12.5 +/- 8.19 vs 12.4 +/- 7.81, d = +0.064, p = 0.836); the mean change
      between the two groups did not reach significance. Quality of life, LDL-c level
      and diet scores improved in the "educated" group only. CONCLUSIONS: The PEGASE
      education program improved risk factors for CVD, although global assessment by
      Framingham score was not significantly different between groups. This program,
      aimed at meeting needs and expectations of patients and physicians, was easily
      implemented in all hospital centres.

PMID- 18830811
TI  - Hostility trait and vascular dilatory functions in healthy Taiwanese.
AB  - Aim It has been demonstrated that brief episodes of mental stress can cause
      transient endothelial dysfunction, which is an important early event in
      atherogenesis. The purpose of this study is to examine the independent effect of
      hostility trait on resting endothelial function. Objective A total of 89 healthy
      adults were recruited. Hostility was measured by the Buss-Durkee Hostility
      Inventory- Chinese Version- Short Form. Vascular dilatory functions were measured
      by using ultrasound imaging of the brachial artery before and after cuff
      occlusion, before and after sublingual nitroglycerin. Conclusion Multiple
      regression analyses revealed the independent negative effect of hostility on flow
      mediated dilation (FMD). And this association is independent from biomedical risk
      factors and other psychological factors, specifically anxiety and depression.
      With respect to Nitroglycerin-induced dilation, none of the psychological risk
      factors were found to have statistically significant contribution.

PMID- 18830812
TI  - Causal beliefs, cardiac denial and pre-hospital delays following the onset of
      acute coronary syndromes.
AB  - Reducing pre-hospital delay is crucial in reducing mortality from acute coronary
      syndrome (ACS). Patient's causal beliefs and coping styles may affect symptom
      appraisal and help-seeking behavior. We examined whether patient's beliefs about
      the causes of their ACS and denial of impact were associated with pre-hospital
      delay. Pre-hospital delay data were collected from 177 patients with ACS.
      Retrospective causal beliefs and cardiac denial of impact were assessed using
      questionnaires. Factor analysis of causal beliefs produced 3 factors; beliefs in
      stress and emotional state, behavioral and clinical risk factors, and in heredity
      as causal influences. Patients with strong beliefs that stress and emotional
      state caused their ACS were more likely to have long pre-hospital delays (>130
      min). There were no significant associations between pre-hospital delay and the
      other two causal belief factors. Patients with greater denial scores were also
      more likely to have long delays than those with low scores. These effects were
      independent of age, gender, education, previous myocardial infarction, history of
      depression and negative affectivity. Cognitive and emotional factors including
      patient's beliefs about causes and avoidant coping help to explain variations in
      pre-hospital delay.

PMID- 18830813
TI  - Common factors in effective HIV prevention programs.
AB  - We propose a set of common factors in evidence-based interventions (EBI) for HIV
      prevention, which cut across theoretical models of behavior change. Three
      existing literatures support this agenda: (1) Common factors in psychotherapy;
      (2) core elements from the Centers for Disease Control and Prevention EBIs; and
      (3) component analyses of EBI. To stimulate discussion among prevention
      researchers, we propose a set of common factors at the highest level of
      abstraction that describe what all effective programs do: (1) establish a
      framework to understand behavior change; (2) convey issue-specific and population
      specific information necessary for healthy actions; (3) build cognitive,
      affective, and behavioral self-management skills; (4) address environmental
      barriers to implementing health behaviors; and (5) provide tools to develop
      ongoing social and community support for healthy actions. A focus on common
      factors will enhance research on new HIV prevention interventions, encourage
      collaboration among researchers, provide guidelines for adapting EBI, and
      simplify and speed the adoption of EBI for providers.

PMID- 18830814
TI  - Clients of female sex workers as a bridging population in Vietnam.
AB  - Understanding bridging behaviors of clients of female sex workers (FSWs) is
      important for projecting and intervening in the spread of sexually transmitted
      infections in Vietnam. The goals of the study were to determine HIV/STI
      prevalence amongst different bridging groups, identify factors associated with
      being potential and active bridgers, and assess the association of drug use and
      unsafe sex with HIV and/or STI prevalence. In April, 2007, 292 clients were
      anonymously interviewed at sex venues in a two-stage time-location cluster
      sampling survey, followed by HIV, syphilis, and HSV-2 testing. Based on condom
      use with both high-risk (FSWs) and low-risk (wives/girlfriends) sexual partners,
      clients were classified as unlikely, potential, or active bridgers. The majority
      of clients were potential or active bridgers (55.8%) who had a significantly
      higher prevalence of herpes simplex type 2 (HSV-2) (21% and 33%, respectively)
      than unlikely bridgers (8.7%). HIV seropositivity was 4.4-fold (95% CI 1.1-17.1)
      higher among those who were HSV-2-positive. Clients of FSWs may be playing a
      major bridging role in transmitting HIV and sexually transmitted infections
      (STIs) in Vietnam. An observed synergistic interaction between drug use and
      condom slippage/breakage emphasizes the importance of proper condom use,
      particularly among drug users.

PMID- 18830815
TI  - Glycine provokes lipid oxidative damage and reduces the antioxidant defenses in
      brain cortex of young rats.
AB  - Patients affected by nonketotic hyperglycinemia (NKH) usually present severe
      neurological symptoms and suffer from acute episodes of intractable seizures with
      leukoencephalopathy. Although excitotoxicity seems to be involved in the brain
      damage of NKH, the mechanisms underlying the neuropathology of this disease are
      not fully established. The objective of the present study was to investigate the
      in vitro effects of glycine (GLY), that accumulate at high concentrations in the
      brain of patients affected by this disorder, on important parameters of oxidative
      stress, such as lipid peroxidation (thiobarbituric acid-reactive substances (TBA
      RS) and chemiluminescence) and the most important non-enzymatic antioxidant
      defense reduced glutathione (GSH) in cerebral cortex from 30-day-old rats. GLY
      significantly increased TBA-RS and chemiluminescence values, indicating that this
      metabolite provokes lipid oxidative damage. Furthermore, the addition of high
      doses of the antioxidants melatonin, trolox (soluble vitamin E) and GSH fully
      prevented GLY-induced increase of lipid peroxidation, indicating that free
      radicals were involved in this effect. GLY also decreased GSH brain
      concentrations, which was totally blocked by melatonin treatment. Finally, GLY
      significantly reduced sulfhydryl group content from a commercial GSH solution,
      but did not oxidize reduced cytochrome C. Our data indicate that oxidative stress
      elicited in vitro by GLY may possibly contribute at least in part to the
      pathophysiology of the neurological dysfunction in NKH.

PMID- 18830816
TI  - Hazard of recurrence and adjuvant treatment effects over time in lymph node
      negative breast cancer.
AB  - BACKGROUND: For patients with axillary lymph node-negative breast cancer,
      benefits from adjuvant therapy are smaller than in node-positive disease and thus
      more selective use is warranted, prompting development of risk profiling to
      identify those most likely to benefit. Examination of the magnitude and changes
      in the hazard of failure over time in node-negative breast cancer may also be
      informative in this regard. METHODS: Among 9,444 participants from five
      randomized trials (accrual 1982-1998) investigating chemotherapy and tamoxifen
      for node-negative breast cancer, we estimated recurrence hazards over time by
      tumor estrogen receptor (ER) status and adjuvant treatment. RESULTS: In patients
      treated by surgery only, we observed the previously noted larger hazard peak
      followed by a rapid decrease in ER-negative patients and smaller but more
      persistent hazard in ER-positive patients. After approximately 48 months, the ER
      positive hazard is greater. For adjuvant treatment, while tamoxifen decreases the
      early hazard in ER-positive patients to that of the chemotherapy-treated ER
      negative group, in later follow-up (beyond 5 years) the hazard for ER-positive
      patients again exceeds that of ER-negative patients. Adding chemotherapy to
      tamoxifen in ER-positive patients results in large early hazard reduction, but in
      later follow-up the hazard converges with those of patients treated by surgery
      only or tamoxifen. CONCLUSIONS: Recurrence hazards over time reveal changes in
      risk that may have biologic and therapeutic strategy relevance. In ER-negative
      tumors, a large early chemotherapy benefit is followed by a consistently low
      recurrence hazard over time. In ER-positive patients, the chemotherapy benefit
      appears concentrated mostly in earlier follow-up, and a greater recurrence risk
      remains.

PMID- 18830817
TI  - PCDDs, PCDFs, PCBs, OC pesticides and mercury in fish and osprey eggs from
      Willamette River, Oregon (1993, 2001 and 2006) with calculated biomagnification
      factors.
AB  - The osprey (Pandion haliaetus) population nesting along the main stem Willamette
      River and lower Santiam River was first studied to evaluate contaminants and
      reproductive rates in 1993 when 78 occupied nests were present. By 2001, the
      population increased to 234 occupied nests, a 13.7% annual rate of population
      increase. A sample egg was collected from each of a series of nests along the
      Upper River (river mile 55-187) in 1993, 2001 and 2006 to evaluate trends of
      persistent contaminants (organochlorine [OC] pesticides, polychlorinated
      biphenyls [PCBs], polychlorinated dibenzo-p-dioxins [PCDDs], and polychlorinated
      dibenzofurans [PCDFs]). Nearly all OC pesticide residues decreased significantly,
      e.g., p, p'-DDE (DDE) from 2,350 to 1,353 to 210 microg/kg wet weight (ww). PCBs
      followed a similar pattern over time, e.g., SigmaPCBs 688 to 245 to 182 microg/kg
      ww, while PCDDs and PCDFs showed a more precipitous decline (often 85-95%)
      between 1993 and 2001, with no egg analyses warranted in 2006. During 2001-2002,
      sample osprey eggs were also collected from nests at three Headwater Reservoirs
      and two lower reaches (Newberg Pool and Tidal Portland) of the Willamette River,
      as well as the lower portion of the Santiam River to evaluate spatial residue
      patterns. Significant differences were seldom detected among the different
      sampling areas for OC pesticides (probably due to small sample sizes), although
      higher concentrations were often seen in the lower reaches, e.g., DDE 901
      microg/kg ww (Headwater Reservoirs), 1,353 (Upper River), 1,384 (Newberg Pool)
      and 2,676 (Tidal Portland). PCB congener concentrations in eggs were usually
      higher in the Tidal Portland reach than at other locations and often
      significantly higher than at the Headwater Reservoirs or Upper River. Mercury
      (first analyzed in eggs in 2001), PCDDs and PCDFs were extremely low in 2001/2002
      with no significant spatial patterns. Whole fish composite samples of largescale
      sucker (Catastomus macrocheilus) and northern pikeminnow (Ptychocheilus
      oregonensis), which account for about 90% of the biomass in the diet of this
      osprey population, were also collected from the Willamette River in 1993 and 2001
      and analyzed for the same contaminants as osprey eggs. Contaminant residues in
      fish from the Upper River decreased between 1993 and 2001, paralleling findings
      for osprey eggs. Likewise, spatial patterns for fish residues paralleled findings
      for osprey eggs from the different reaches in 2001. A second empirical estimate
      of biomagnification factors (BMFs) from fish to osprey eggs for OC pesticides,
      PCBs, PCDDs and PCDFs (ww and lipid weight [lw] basis) was calculated based on
      residue data collected in 2001. The two independent BMF estimates (1993 and 2001)
      for each contaminant from the Upper River provide a measure of consistency, e.g.,
      DDE (ww) 87 and 79, (lw) 103 and 112; SigmaPCBs (ww) 11 and 8.4, (lw) 13 and 12.
      Mercury did not biomagnify from fish to osprey eggs (BMF = 0.60). Legacy
      contaminants investigated had limited (perhaps only DDE), if any, effects on
      reproductive success of the increasing osprey population nesting along the
      Willamette River by 2001.

PMID- 18830818
TI  - Passaged goat costal chondrocytes provide a feasible cell source for
      temporomandibular joint tissue engineering.
AB  - Costal cartilage is commonly harvested for various types of facial reconstructive
      surgery. The ability of costal chondrocytes (CCs) to produce relevant
      extracellular matrix, including glycosaminoglycans (GAGs) and collagens, makes
      them an appealing cell source for fibrocartilage engineering. In order to obtain
      enough cells for tissue engineering, however, cell expansion will likely be
      necessary. This study examined CCs at passages 0, 1, 3, and 5, as well as
      temporomandibular (TMJ) disc cells, in a scaffoldless tissue engineering
      approach. It was hypothesized that earlier passage constructs would have more
      cartilaginous proteins and less fibrocartilaginous proteins. TMJ disc constructs
      had over twice the collagen content of any other group, as well as the largest
      tensile properties; however, the substantial contraction of the constructs and
      limited cell numbers make it a non-feasible cell source for tissue engineering.
      In general, statistical differences in mechanical properties or collagen content
      of the various CC groups were not observed; however, significantly more GAG was
      produced in the passaged CCs than the primary CCs. More collagen type II was also
      observed in some of the passaged groups. These results suggest not only
      feasibility but potential superiority of passaged CCs over primary CCs, which may
      lead to functional engineered fibrocartilage.

PMID- 18830819
TI  - Social patterning of chronic disease risk factors in a Latin American city.
AB  - Most studies of socioeconomic status (SES) and chronic disease risk factors have
      been conducted in high-income countries, and most show inverse social gradients.
      Few studies examine these patterns in lower- or middle-income countries. Using
      cross-sectional data from a 2005 national risk factor survey in Argentina (a
      middle-income country), we investigated the associations of individual- and area
      level SES with chronic disease risk factors (body mass index [BMI], hypertension,
      and diabetes) among residents of Buenos Aires. Associations of risk factors with
      income and education were estimated after adjusting for age, sex (except in sex
      stratified models), and the other socioeconomic indicators. BMI and obesity were
      inversely associated with education and income for women, but not for men (e.g.,
      mean differences in BMI for lowest versus highest education level were 1.55
      kg/m2, 95%CI = 0.72-2.37 in women and 0.17 kg/m2, 95%CI = -0.72-1.06 in men). Low
      education and income were also associated with increased odds of hypertension
      diagnosis in all adults (adjusted odds ratio [AOR] = 1.48, 95%CI = 0.99-2.20 and
      AOR = 1.50, 95%CI = 0.99-2.26 for the lowest compared to the highest education
      and income categories, respectively). Lower education was strongly associated
      with increased odds of diabetes diagnosis (AOR = 4.12, 95%CI = 1.85-9.18 and AOR
      = 2.43, 95%CI = 1.14-5.20 for the lowest and middle education categories compared
      to highest, respectively). Area-level education also showed an inverse
      relationship with BMI and obesity; these results did not vary by sex as they did
      at the individual level. This cross-sectional study of a major urban area
      provides some insight into the global transition with a trend toward
      concentrations of risk factors in poorer populations.

PMID- 18830820
TI  - Modelling the role of intrinsic electric fields in microtubules as an additional
      control mechanism of bi-directional intracellular transport.
AB  - Active transport is essential for cellular function, while impaired transport has
      been linked to diseases such as neuronal degeneration. Much long distance
      transport in cells uses opposite polarity molecular motors of the kinesin and
      dynein families to move cargos along microtubules. It is clear that many types of
      cargo are moved by both sets of motors, and frequently in a reverse direction.
      The general question of how the direction of transport is regulated is still
      open. The mechanism of the cell's differential control of diverse cargos within
      the same cytoplasmic background is still unclear as is the answer to the question
      how endosomes and mitochondria move to different locations within the same cell.
      To answer these questions we postulate the existence of a local signaling
      mechanism used by the cell to specifically control different cargos. In
      particular, we propose an additional physical mechanism that works through the
      use of constant and alternating intrinsic (endogenous) electric fields as a means
      of controlling the speed and direction of microtubule-based transport. A specific
      model is proposed and analyzed in this paper. The model involves the rotational
      degrees of freedom of the C-termini of tubulin, their interactions and the
      coupling between elastic and dielectric degrees of freedom. Viscosity of the
      solution is also included and the resultant equation of motion is found as a
      nonlinear elliptic equation with dissipation. A particular analytical solution of
      this equation is obtained in the form of a kink whose properties are analyzed. It
      is concluded that this solution can be modulated by the presence of electric
      fields and hence may correspond to the observed behavior of motor protein
      transport along microtubules.

PMID- 18830821
TI  - Polyunsaturated fatty acid modulation of voltage-gated ion channels.
AB  - Arachidonic acid (AA) was found to inhibit the function of whole-cell voltage
      gated (VG) calcium currents nearly 16 years ago. There are now numerous examples
      demonstrating that AA and other polyunsaturated fatty acids (PUFAs) modulate the
      function of VG ion channels, primarily in neurons and muscle cells. We will
      review and extract some common features about the modulation by PUFAs of VG
      calcium, sodium, and potassium channels and discuss the impact of this modulation
      on the excitability of neurons and cardiac myocytes. We will describe the fatty
      acid nature of the membrane, how fatty acids become available to function as
      modulators of VG channels, and the physiologic importance of this type of
      modulation. We will review the evidence for molecular mechanisms and assess our
      current understanding of the structural basis for modulation. With guidance from
      research on the structure of fatty acid binding proteins, the role of lipids in
      gating mechanosensitive (MS) channels, and the impact of membrane lipid
      composition on membrane-embedded proteins, we will highlight some avenues for
      future investigations.

PMID- 18830822
TI  - A novel reversible pH-triggered release immobilized enzyme system.
AB  - A novel immobilized enzyme system supported by poly(acrylic acid/N,N'-methylene
      bisacryl-amide) hydrogel microspheres was prepared. This system exhibited
      characteristics of reversible pH-triggered release. The morphology, size, and
      chemical structure were examined through optical microscopy, particle size
      analyzer, and Fourier transform infrared spectrometer. Immobilization and release
      features were further investigated under different conditions, including pH,
      time, and microsphere quantity. Results showed the microspheres were regularly
      spherical with 3.8 approximately 6.6 microm diameter. Loading efficiencies of
      bovine serum albumin immobilized by gel entrapment and adsorption methods were
      93.9% and 56.2%, respectively. The pH-triggered protein release of the system
      occurred when medium pH was above 6.0, while it was hardly detected when medium
      pH was below 6.0. Release efficiencies of entrapped and adsorbed protein were
      6.38% and 95.0%, respectively. Hence, adsorption method was used to immobilize
      trypsin. Loading efficiency of 77.2% was achieved at pH 4.0 in 1 h. Release
      efficiency of 91.6% was obtained under optimum pH catalysis condition set at 8.0
      and trypsin was free in solutions with retention activity of 63.3%. And 51.5% of
      released trypsin could be reloaded in 10 min. The results indicate this kind of
      immobilized enzyme system offers a promising alternative for enzyme recovery in
      biotechnology.

PMID- 18830823
TI  - Pervaporation separation of thiophene-heptane mixtures with polydimethylsiloxane
      (PDMS) membrane for desulfurization.
AB  - Cross-linked polydimethylsiloxane (PDMS)-polyetherimide (PEI) composite membranes
      were prepared, in which asymmetric microporous PEI membrane prepared with phase
      inversion method was acted as the microporous supporting layer in the flat-plate
      composite membrane. Membrane characterization was conducted by Fourier transform
      infrared and scanning electronic microscopy analysis. The composite membranes
      were employed in pervaporation separation of n-heptane-thiophene mixtures. Effect
      of amount of PDMS, cross-linking temperature, amount of cross-linking agent, and
      cross-linking time on the separation efficiency of n-heptane-thiophene mixtures
      was investigated experimentally. Experiment results demonstrated that 80-100
      degrees degrees C of cross-linking temperature was more preferable for practical
      application, as the amount of cross-linking agent was up to 20 wt.%, and 25 wt.%
      of PDMS amount was more optimal as far as flux and sulfur enrichment factor were
      concerned. In addition, the swelling degree of and stableness of composite
      membrane during long-time operation were studied, which should be significant for
      practical application.

PMID- 18830824
TI  - Succinic acid production from acid hydrolysate of corn fiber by Actinobacillus
      succinogenes.
AB  - Dilute acid hydrolysate of corn fiber was used as carbon source for the
      production of succinic acid by Actinobacillus succinogenes NJ113. The optimized
      hydrolysis conditions were obtained by orthogonal experiments. When corn fiber
      particles were of 20 mesh in size and treated with 1.0% sulfuric acid at 121
      degrees C for 2 h, the total sugar yield could reach 63.3%. It was found that
      CaCO(3) neutralization combined with activated carbon adsorption was an effective
      method to remove fermentation inhibitors especially furfural that presented in
      the acid hydrolysate of corn fiber. Only 5.2% of the total sugar was lost, while
      91.9% of furfural was removed. The yield of succinic acid was higher than 72.0%
      with the detoxified corn fiber hydrolysate as the carbon source in anaerobic
      bottles or 7.5 L fermentor cultures. It was proved that the corn fiber
      hydrolysate could be an alternative to glucose for the production of succinic
      acid by A. succinogenes NJ113.

PMID- 18830825
TI  - Characterization of the interactions of lysozyme with DNA by surface plasmon
      resonance and circular dichroism spectroscopy.
AB  - Association with nucleic acid has been recognized as a unique role of lysozyme
      and may explain why lysozyme was called a killer protein against HIV infection.
      In the present study, we characterized the interactions of lysozyme and its
      derived peptides with a biotin-labeled pUC19 plasmid DNA. Real-time detection of
      the macromolecular interaction was performed using the SPR (surface plasmon
      resonance) spectroscopy. The SPR sensorgrams were analyzed and the association
      and dissociation rate constants as well as the dissociation equilibrium constant
      KD were, thus, estimated. The results reveal that other than the electrostatic
      interactions between the basic protein and the nucleotide sequences carrying
      negative charges, the specific DNA-binding motifs at the N- and C-termini of
      lysozyme were also involved in the interactions. The nonapeptide RAWVAWRNR (aa
      107-115 of lysozyme) reported previously to block HIV-1 viral entrance and
      replication was also able to bind DNA with its KD value comparable to that of
      histones. The possibilities of ligand-binding-induced conformational changes were
      investigated using the circular dichroism spectroscopy. The CD spectra (200-320
      nm) reveal that the conformational changes indeed occur as the spectra of
      lysozyme-DNA interactions are much less at the major trough region than the sum
      of individual spectra. The interaction of lysozyme with DNA molecules may
      interfere with DNA replication, modulate gene expression, and block bacterial and
      viral infections. These all suggest that human lysozyme may represent part of the
      innate immune system with a very broad protective spectrum.

PMID- 18830826
TI  - A new microplate screening method for the simultaneous activity quantification of
      feruloyl esterases, tannases, and chlorogenate esterases.
AB  - Feruloyl, chlorogenate esterases, and tannases are enzymes useful in phenolic
      modifications of pharmaceutical relevance as protectors against several
      degenerative human diseases. Therefore, there is a growing interest in
      discovering new sources of these enzymes. However, traditional methods for their
      activity measurements are time-consuming and poorly adapted for high-throughput
      screening. In this study, a successful new microplate high-throughput screening
      method for the simultaneous quantification of all mentioned activities is
      demonstrated. This method allows the detection of activities as low as 1.7 mU ml(
      1). Furthermore, reaction rates increased proportionally with the amount of
      enzyme added, and no interferences with the other commercial hydrolases tested
      were found. The utility of the method was demonstrated after simultaneously
      screening feruloyl, chlorogenate esterase, and tannase activities in solid state
      fermentation extracts obtained during the kinetics of production of 20 fungal
      strains. Among these, seven strains were positive for at least one of the
      esterase activities tested. This result shows the potential for the rapid routine
      screening assays for multiple samples of moderate low to high enzymatic levels.

PMID- 18830827
TI  - Antimicrobial and antineoplasic activity of Pleurotus ostreatus.
AB  - The objectives of this work were to evaluate the antimicrobial and antineoplasic
      activity of Pleurotus ostreatus DSM 1833. To study the antimicrobial activity,
      the following extracts were prepared: water infusion of the fresh fruiting bodies
      (B1), dehydrated fruiting bodies (B2), fresh mycelium (M1), and dehydrated
      mycelium (M2). Polysaccharides from the fresh mycelium were also obtained by
      water infusion followed by ethanol treatment (EP). The extracts were tested
      against Candida albicans, Escherichia coli, and Bacillus subtilis. To investigate
      the antineoplasic effect of P. ostreatus, the culture broth in natura, the
      extract from the culture broth (ECB), and the extract from the fruiting bodies
      were tested in female Swiss albino mice inoculated with the Ehrlich ascitic tumor
      (EAT). B1, B2, and M1 showed more than 50.0% inhibition against C. albicans. M2
      presented a high degree of inhibition against E. coli (87.5%) and B. subtilis
      (57.5%), while EP was not effective. All the tested substances inhibited the
      development of EAT at levels near 70% when injected intraperitoneally in mice.
      The highest tumor inhibition (76%) was achieved for the treatment with ECB. The
      intragastric treatment did not promote any reduction in tumor cell development,
      independent of the test substance.

PMID- 18830828
TI  - Effects of neuregulin on expression of MMP-9 and NSE in brain of
      ischemia/reperfusion rat.
AB  - The aim is to investigate the effects of neuregulin-1beta (NRG-1beta) on
      expression of matrix metalloproteinase-9 (MMP-9) and neuron-specific enolase
      (NSE) in brain tissue in rats following cerebral ischemia/reperfusion. One
      hundred and fifty adult healthy male Wistar rats were used in the present study.
      Ten of them were randomized into a sham-operation group (n = 10) and the rest
      suffered surgery operation of middle cerebral artery occlusion/reperfusion with
      intraluminal monofilament suture from the left external-internal carotid artery.
      As a result, 100 rats of successful models were randomly divided into a control
      group (n = 50) and a treatment group (n = 50). Rats in the treatment group were
      injected 1.5% NRG-1beta at a dosage of 0.3 microg/kg from the stump of the left
      external carotid artery into the internal carotid artery. The expressions of MMP
      9 and NSE proteins were determined by immunohistochemical, immunofluorescent
      double labeling, and Western blot assay. Ischemia/reperfusion induced
      morphological changes of brain tissue, including neurocyte shrinkage, chromatin
      condensation, nuclei fragment, and gliacyte and endothelial cell swelling. NRG
      1beta obviously reduced and delayed the cerebral damage. With the duration of
      ischemia, the expression of MMP-9 gradually increased in the control group. NRG
      1beta decreased the level of MMP-9 compared with that in the control group (P <
      0.01). NSE immunoreaction transiently elevated at the early stage of cerebral
      ischemia insult, and then gradually decreased in the control group. The
      administration of NRG-1beta significantly increased the level of NSE, and thus
      delayed the time and the degree of neuron damage. There were statistical
      differences in contrast to the control group (P < 0.01). There was no
      relationship between the expressions of the two proteins. MMP-9 might aim at
      various target cells at different stages and contribute to the inflammatory
      reaction after cerebral ischemia-reperfusion insult. NRG-1beta inhibits the
      activation of MMP-9 and development of inflammation, enhances the activity of
      NSE, improves the microenvironment of neuron survivals, and delays the phase of
      irreversible neuron necrosis. Therefore, NRG-1beta may play a neuroprotective
      role in cerebral ischemia/reperfusion.

PMID- 18830829
TI  - Prostate-specific antigen in the cerebrospinal fluid: a marker of local disease.
AB  - Leptomeningeal involvement from prostate cancer is a rare complication with
      dismal prognosis. Prostate-specific antigen in the cerebrospinal fluid may be
      found elevated and can be used as a marker for local disease. We present the case
      of a patient with prostate cancer and leptomeningeal metastases who had high
      levels of prostate-specific antigen in the cerebrospinal fluid.

PMID- 18830830
TI  - Areas of concentration in family medicine residency training.

PMID- 18830831
TI  - A pilot survey of community health services in China.

PMID- 18830832
TI  - Lost in translation: the confusing lexicon of the "new" NIH.

PMID- 18830833
TI  - Promoting medical humanism: design and evaluation of an online curriculum.
AB  - To provide patient-centered care, physicians must be well trained in the concepts
      and methods of humanistic practice. Educational efforts to promote humanism may
      help to overcome the counter-training of the hidden medical school curriculum,
      responsible for a decline in empathy and idealism over the course of medical
      training. The online component of the clerkship in family medicine at Boston
      University introduced activities founded on reflection, self-awareness,
      collaborative learning, and applied practice to successfully promote student
      confidence in three key areas of humanistic practice.

PMID- 18830834
TI  - Confessions of a first-year medical student.

PMID- 18830836
TI  - Doctors, writing, and HIPAA.

PMID- 18830837
TI  - Resident physician burnout: is there hope?
AB  - BACKGROUND: Prevalent among resident physicians, burnout has been associated with
      absenteeism, low job satisfaction, and medical errors. Little is known about the
      number and quality of interventions used to combat burnout. METHODS: We performed
      a systematic review of the literature using MEDLINE and PubMed databases. We
      included English-language articles published between 1966 and 2007 identified
      using combinations of the following medical subject heading terms: burnout,
      intervention studies, program evaluation, internship and residency, graduate
      medical education, medical student, health personnel, physician, resident
      physician, resident work hours, and work hour limitations. Additional articles
      were also identified from the reference lists of manuscripts. The quality of
      research was graded with the Strength of Evidence Taxonomy (SORT) from highest
      (level A) to lowest (level C). RESULTS: Out of 190 identified articles, 129 were
      reviewed. Nine studies met inclusion criteria, only two of which were randomized,
      controlled trials. Interventions included workshops, a resident assistance
      program, a self-care intervention, support groups, didactic sessions, or stress
      management/coping training either alone or in various combinations. None of the
      studied interventions achieved an A-level SORT rating. CONCLUSIONS: Despite the
      potentially serious personal and professional consequences of burnout, few
      interventions exist to combat this problem. Prospective, controlled studies are
      needed to examine the effect of interventions to manage burnout among resident
      physicians.

PMID- 18830838
TI  - Anatomy correlations: introducing clinical skills to improve performance in
      anatomy.
AB  - BACKGROUND AND OBJECTIVES: Gross anatomy is one of the preclinical cornerstones
      of medical education, but many practitioners feel that medical students'
      knowledge of anatomy is inadequate. To help students understand the clinical
      relevance of anatomy studies, Ohio State University faculty developed a course
      called "Anatomy Correlations." This course introduces students to basic physical
      examination techniques correlated to gross anatomy dissections and allows them to
      practice techniques learned. METHODS: Anatomy grades prior to the introduction of
      the course were compared with anatomy grades after the introduction of the course
      to see if the course improved knowledge of gross anatomy. Analysis controlled for
      initial differences in academic aptitude. RESULTS: Students taking the course in
      its new form scored higher in anatomy than did students taking anatomy before the
      course was offered. CONCLUSION: Introducing physical examination skills that
      correlate with anatomy studies can lead to improvement in anatomy scores.

PMID- 18830839
TI  - Prayer for health and primary care: results from the 2002 National Health
      Interview Survey.
AB  - BACKGROUND AND OBJECTIVES: Prayer for health (PFH) is common; in 2002, 35% of US
      adults prayed for their health. We examined the relationship of PFH and primary
      care visits, with a special focus on African American women, using data from the
      2002 National Health Interview Survey (NHIS). METHODS: We used chi-square
      analyses to compare the demographic (age group, gender, race, region, marital
      status, educational level, ethnicity) and health-related covariates (alcohol use,
      smoking status, and selected medical conditions) between individuals who did and
      did not pray for their health in the past year. Univariate associations between
      PFH and visit to primary care provider (PCP), with Mantel-Haenszel adjustment for
      confounding, were determined. Multivariate regression was used to determine
      independent factors associated with PFH and PCP visit, with SUDAAN to adjust for
      the clustered survey design. RESULTS: Subjects who prayed were more likely to be
      female, older than 58, Black, Southern, separated, divorced or widowed, and
      nondrinkers. Subjects who prayed were also more likely to have seen a PCP within
      the past year. Black women who prayed were also more likely to see a PCP.
      CONCLUSIONS: These findings suggest that people who pray for their health do so
      in addition to, not instead of, seeking primary care. This finding is maintained
      but with a smaller effect size, in Black women.

PMID- 18830840
TI  - Primary care for adults with physical disabilities: perceptions from consumer and
      provider focus groups.
AB  - BACKGROUND AND OBJECTIVES: Family physicians lack data on how best to address the
      needs of adults with physical disabilities. We undertook this study to understand
      how consumers, educators, and other professionals perceive primary care for
      people with disabilities. METHODS: We conducted six focus groups, three with 27
      health professionals in primary care practices affiliated with an urban
      university medical center and three with 19 local adults, ages 21-64 years, with
      physical disabilities. From transcribed recordings, three investigators conducted
      separate content analyses. Independent author reviews and participant review
      confirmed saturation and agreement for major themes. RESULTS: All groups
      perceived that generalist physicians and other health professionals need more
      education about disability issues. Multiple barriers limit care, including
      physical access and transportation, funding, limitations in professionals'
      knowledge and attitudes, communication gaps, and health systems failures. Both
      consumers and professionals recommended reducing barriers by educating
      professionals and trainees about disabilities and resources, improving provider
      patient communication, enhancing physical access (eg, high-low examination
      tables, wide automatic doors, high-contrast signs and lighting, wheelchair
      scales), and increasing appointment times. CONCLUSIONS: Primary care must address
      the unmet needs of people with disabilities. Family medicine educators can begin
      by teaching learners how to coordinate care, access resources, and communicate
      about disability issues.

PMID- 18830841
TI  - Older patients' views on the relationship between depression and heart disease.
AB  - BACKGROUND AND OBJECTIVES: Longitudinal studies have found evidence of
      associations between coronary heart disease and clinical depression. We sought to
      understand older patients' views regarding relationships between depression and
      heart disease to facilitate patient-provider communication about heart disease
      and depression and to lay the groundwork for designing interventions. METHODS:
      The design was a qualitative study using semi-structured interviews. In all, 33
      primary care patients 65 years and over with dysphoria, anhedonia, hopelessness,
      worthlessness, or sleep disturbance who were taking at least one medication
      targeting cardiovascular risk factors were interviewed in the office of their
      primary care clinician. Participants were asked open-ended questions about
      depression and heart disease and their treatment. A multidisciplinary research
      team coded the transcripts and identified key themes. RESULTS: Participants gave
      clear descriptions of how heart disease can lead to depression and depression can
      lead to heart disease. Participants supported treating depression immediately in
      the context of heart disease and generally preferred integrated care.
      CONCLUSIONS: Depression treatment may be more acceptable if discussed in terms of
      overall cardiovascular risk. Our results support the integration of depression
      management with management for risk factors for cardiovascular disease.

PMID- 18830842
TI  - The need for medical ethics education in family medicine training.
AB  - Professional and accreditation organizations have endorsed medical ethics as a
      fundamental component of education for family medicine trainees. Yet various
      obstacles combine to work against the continuation of formal medical ethics
      education beyond medical school and into residency training. This article reviews
      the current consensus on the scope and objectives of medical ethics education in
      the context of family medicine training. The need for, and outcomes of, medical
      ethics teaching are analyzed on the basis of the available evidence. Recent
      trends in medical education that potentially influence graduate medical ethics
      training are also discussed (specifically ethics training in medical schools and
      the priority given to training in professionalism). This review shows a strong
      evidence-based need to provide medical ethics education for family physicians in
      training, a need that is apparent on many levels. The current reliance on medical
      school ethics education and emphasis on professionalism does not answer this
      need. A well-constructed course in medical ethics for family medicine trainees
      can teach an array of competencies stipulated by professional and accreditation
      agencies as important in the practice of family medicine. Educators must strive
      to overcome barriers and provide formal medical ethics programs to better prepare
      family physicians for modern professional roles.

PMID- 18830843
TI  - Helping ourselves by empowering others--it's not enough to do no harm.

PMID- 18830847
TI  - [Consensus on physical health of patients with schizophrenia from the Spanish
      Societies of Psychiatry and Biological Psychiatry].
AB  - INTRODUCTION: Schizophrenia has traditionally been associated with higher rates
      of physical comorbidity and excess mortality. OBJECTIVE: To develop a Spanish
      consensus document concerning the physical health of patients with schizophrenia
      and the interventions required to reduce the over-morbidity and over-mortality of
      these patients. Method. The process consisted of: a) systematic review of the
      literature in the Medline database up to January 2006 and manual review of the
      bibliographical references of the papers obtained; b) reviews of national and
      international guides by the coordinating committee and medical specialist acting
      as expert advisors; c) multidisciplinary consensus meetings, and d) editing of
      the final consensus document. RESULTS: Compared to the general population,
      patients with schizophrenia present higher rates of infection (HBV, HCV, HIV),
      endocrine/metabolic disorders, cardiac and respiratory diseases (over-morbidity)
      and higher global death risk, as well as death from natural causes--basically
      respiratory, cardiovascular and oncological diseases (over-mortality). As a
      guide, therefore, this document proposes a series of interventions to be
      performed by psychiatrists to reduce the current rates. CONCLUSIONS: Given the
      over-morbidity and overmortality of patients with schizophrenia, awareness of
      these aspects should be increased among primary healthcare providers and
      specialists, including psychiatrists, and physical health problems should be
      incorporated into psycho-educational programs, and treatment compliance and
      severe mental disorder treatment units.

PMID- 18830848
TI  - [Attention deficit/hyperactivity disorder: burden of the disease according to
      subtypes in recently diagnosed children].
AB  - INTRODUCTION: Attention-Deficit/Hyperactivity Disorder (ADHD) is associated with
      deterioration of several dimensions of quality of life (QoL) and with the
      development of comorbid psychiatric disorders. The objective of the present study
      is to evaluate the burden of illness of ADHD subtypes in untreated newly
      diagnosed children in Spain. METHODS: We recruited 124 children (80 combined, 25
      inattentive and 19 hyperactive-impulsive subtype) aged 6-12 years with untreated
      newly diagnosed Diagnostic and Statistical Manual of Mental Disorders, 4th
      edition DSM-IV) ADHD. We collected socio-demographic, clinical (Attention
      Deficit/Hyperactivity Disorder Rating Scale ADHD-RS], Conner's Parent Rating
      Scale-Revised: Short Form [CPRS:R-S], Clinical Global Impression-Severity [CGI
      S], Kiddie Schedule for Affective Disorders and Schizophrenia for School Aged
      Children-Present and Lifetime Version [K-SADS-PL], intelligence Quotient [IQ]),
      Quality of Life (QoL), Child Health Questionnaire-Parent Form 50 CHQ-PF50),
      academic performance and health care resources utilization data. We investigated
      the correlations between ADHD symptom severity and QoL, academic performance and
      time from onset of symptoms to diagnosis. RESULTS: QoL of children with combined
      type ADHD was rated as significantly worse in patients with predominance of
      hyperactivity/impulsivity for most of the domains. Inattentive-type children also
      had worse ratings than patients with hyperactivity/impulsivity predominance in
      most of the domains. The ADHD Index of Conner's Parent Rating Scale-Revised:
      Short Form (CPRS-R:S) was significantly lower in hyperactive/impulsive patients.
      We found no differences across subtypes in IQ, academic performance and health
      care resources utilization. Higher ADHD symptom severity was associated to poor
      QoL. CONCLUSIONS: Combined and inattentive subtypes are associated with greater
      disorder severity, more comorbid psychiatric disorders, and worse QoL than the
      subtype with hyperactivity/impulsivity predominance.

PMID- 18830849
TI  - Abstracts of Acute Cardiac Care 2008. October 25-28, 2008. Versailles, France.

PMID- 18830856
TI  - Biomarkers has now been in existence for over 12 years. Editorial.

PMID- 18830857
TI  - The discovery and early validation of novel plasma biomarkers in mild-to-moderate
      Alzheimer's disease patients responding to treatment with rosiglitazone.
AB  - Recent advances in clinical, pathological and neuroscience studies have
      identified disease-modifying therapeutic approaches for Alzheimer's disease that
      are now in clinical trials. This has highlighted the need for reliable and
      convenient biomarkers for both early disease diagnosis and a rapid signal of drug
      efficacy. We describe the identification and assessment of a number of candidate
      biomarkers in patients with Alzheimer's disease and the correlation of those
      biomarkers with rosiglitazone therapeutic efficacy, as represented by a change in
      the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog). Plasma from 41
      patients with Alzheimer's disease were analysed by open platform proteomics at
      baseline and after receiving 8 mg rosiglitazone for 24 weeks. From a comparison
      of protein expression following treatment with rosiglitazone, 97 proteins were
      observed to be differentially expressed with a p-value<0.01. From this analysis
      and comparison to recently published data from our laboratory, a prioritized list
      of 10 proteins were analysed by immunoassay and/or functional assay in a wider
      set of samples from the same clinical study, representing a rosiglitazone dose
      response, in order to verify the changes observed. A number of these proteins
      appeared to show a correlation with change in ADAS-Cog at the higher treatment
      doses compared with the placebo. Alpha-2-macroglobulin, complement C1 inhibitor,
      complement factor H and apolipoprotein E expression showed a correlation with
      ADAS-Cog score at the higher doses (4 mg and 8 mg). These results are discussed
      in light of the pathology and other recently published data.

PMID- 18830858
TI  - A developmental theory of synaesthesia, with long historical roots: a comment on
      Hochel & Milan.
AB  - The recent surge of scientific investigation into synaesthesia, ably reviewed by
      Hochel and Milan (2008), is representative of an increasing recognition that our
      various sensory modalities are intimately interconnected rather than separate.
      The origin of these interconnections is the subject of an intriguing theory by
      Maurer and Maurer (1988). They suggest that all of us begin life as synaesthetes,
      with subsequent neural development reducing the connections among the senses. We
      present some historical roots of the idea that human life begins with the senses
      intertwined. The influential 18th-century philosopher Jean-Jacques Rousseau
      described an early theory of child development in his book Emile (1762),
      hypothesizing that if "a child had at its birth the stature and strength of a man
      ... all his sensations would be united in one place, they would exist only in the
      common 'sensorium'." A half-century later, a young Mary Shelley (1818) brought
      this idea into popular culture with the Frankenstein creature's recollection of
      his early experience: "A strange multiplicity of sensations seized me, and I saw,
      felt, heard, and smelt, at the same time; and it was, indeed, a long time before
      I learned to distinguish between the operations of my various senses." William
      James in The Principles of Psychology (1890) expressed a similar idea. In this
      context, the assumption of many 20th-century scientists that the senses were
      largely separate appears to be an historical aberration.

PMID- 18830859
TI  - The role of sensorimotor learning in the perception of letter-like forms:
      tracking the causes of neural specialization for letters.
AB  - Functional specialization in the brain is considered a hallmark of efficient
      processing. It is therefore not surprising that there are brain areas specialized
      for processing letters. To better understand the causes of functional
      specialization for letters, we explore the emergence of this pattern of response
      in the ventral processing stream through a training paradigm. Previously, we
      hypothesized that the specialized response pattern seen during letter perception
      may be due in part to our experience in writing letters. The work presented here
      investigates whether or not this aspect of letter processing-the integration of
      sensorimotor systems through writing-leads to functional specialization in the
      visual system. To test this idea, we investigated whether or not different types
      of experiences with letter-like stimuli ("pseudoletters") led to functional
      specialization similar to that which exists for letters. Neural activation
      patterns were measured using functional magnetic resonance imaging (fMRI) before
      and after three different types of training sessions. Participants were trained
      to recognize pseudoletters by writing, typing, or purely visual practice. Results
      suggested that only after writing practice did neural activation patterns to
      pseudoletters resemble patterns seen for letters. That is, neural activation in
      the left fusiform and dorsal precentral gyrus was greater when participants
      viewed pseudoletters than other, similar stimuli but only after writing
      experience. Neural activation also increased after typing practice in the right
      fusiform and left precentral gyrus, suggesting that in some areas, any motor
      experience may change visual processing. The results of this experiment suggest
      an intimate interaction among perceptual and motor systems during pseudoletter
      perception that may be extended to everyday letter perception.

PMID- 18830860
TI  - Treatment approaches for dual diagnosis clients in England.
AB  - INTRODUCTION: Dual diagnosis (DD, co-occurrence of substance use and mental
      health problems) prevalence data in England are limited to specific regions and
      reported rates vary widely. Reliable information on actual service provision for
      dual diagnosis clients has not been collated. Thus a national survey was carried
      out to estimate dual diagnosis prevalence in treatment populations and describe
      the service provision available for this client population in drug/alcohol (DAS)
      and mental health services (MHS). DESIGN: A questionnaire was sent to managers of
      706 DAS and 2374 MHS. Overall, 249 (39%) DAS and 493 (23%) MHS participated in
      the survey. RESULTS: In both DAS and MHS, around 32% of clients were estimated to
      have dual diagnosis problems. However, fewer than 50% of services reported
      assessing clients for both problem areas. Regarding specific treatment
      approaches, most services (DAS: 88%, MHS: 87%) indicated working jointly with
      other agencies. Significantly fewer services used joint protocols (DAS: 55%, MHS:
      48%) or shared care arrangements, including access to external drug/alcohol or
      mental health teams (DAS: 47%, MHS: 54%). Only 25% of DAS and 17% of MHS employed
      dual diagnosis specialists. CONCLUSIONS: Dual diagnosis clients constitute a
      substantial proportion of clients in both DAS and MHS in England. Despite recent
      policy initiatives, joint working approaches tend to remain unstructured.

PMID- 18830861
TI  - Final safety assessment of Coal Tar as used in cosmetics.
AB  - Coal Tar is a semisolid by-product obtained in the destructive distillation of
      bituminous coal, which functions in cosmetic products as a cosmetic biocide and
      denaturant--antidandruff agent is also listed as a function, but this is
      considered an over-the-counter (OTC) drug use. Coal Tar is a nearly black,
      viscous liquid, heavier than water, with a naphthalene-like odor and a sharp
      burning taste, produced in cooking ovens as a by-product in the manufacture of
      coke. Crude Coal Tar is composed of 48% hydrocarbons, 42% carbon, and 10% water.
      In 2002, Coal Tar was reported to the Food and Drug Administration (FDA) to be
      used in four formulations, all of which appear to be OTC drug products. Coal Tar
      is monographed by the FDA as Category I (safe and effective) OTC drug ingredient
      for use in the treatment of dandruff, seborrhoea, and psoriasis. Coal Tar is
      absorbed through the skin of animals and humans and is systemically distributed.
      In short-term studies, mice fed a diet containing Coal Tar found it unpalatable,
      but no adverse effects were reported other than weight loss; rats injected with
      Coal Tar experienced malaise in one study and decreased water intake and
      increased liver weights in another; rabbits injected with Coal Tar residue
      experienced eating avoidance, respiratory difficulty, sneezing, and weight loss.
      In a subchronic neurotoxicity study using mice, a mixture of phenols, cresols,
      and xylenols at concentrations approximately equal to those expected in Coal Tar
      extracts produced regionally selective effects, with a rank order of corpus
      striatum > cerebellum > cerebral cortex. Coal Tar applied to the backs of guinea
      pigs increases epidermal thickness. Painting female rabbits with tar decreases
      the absolute and relative weights of the ovaries and decreased the number of
      interstitial cells in the ovary. Four therapeutic Coal Tar preparations used in
      the treatment of psoriasis were mutagenic in the Ames assay. Urine and blood from
      patients treated with Coal Tar were genotoxic in bacterial assays. Coal Tar was
      genotoxic in a mammalian genotoxicity assay and induced DNA adducts in various
      tissue types. Chronic exposure of mice to Coal Tar significantly decreased
      survival and liver neoplasms were seen in a significant dose-related trend; in
      other studies using mice lung tumors and perianal skin cancers were found. Coal
      Tar was comedogenic in three small clinical studies. Folliculitis is associated
      with the prolonged use of some tars. Several published reports describe cases of
      contact sensitivity to Coal Tar. Polycyclic aromatic hydrocarbons, which make up
      Coal Tar, are photosensitizers and cause phototoxicity by an oxygen-dependent
      mechanism. A retrospective study of the reproductive toxicity of Coal Tar in
      humans compared exposed women to controls and found little difference in
      spontaneous abortion and congenital disorders. Cancer epidemiology studies of
      patients who have received Coal Tar therapy of one form or other have failed to
      link treatment with an increase in the risk of cancer. Although the Cosmetic
      Ingredient Review (CIR) Expert Panel believes that Coal Tar use as an
      antidandruff ingredient in OTC drug preparations is adequately addressed by the
      FDA regulations, the Panel also believes that the appropriate concentration of
      use of Coal Tar in cosmetic formulations should be that level that does not have
      a biological effect in the user. Additional data needed to make a safety
      assessment include product types in which Coal Tar is used (other than as an OTC
      drug ingredient), use concentrations, and the maximum concentration that does not
      induce a biological effect in users.

PMID- 18830862
TI  - Final report on the safety assessment of methoxyisopropanol and methoxyisopropyl
      acetate as used in cosmetics.
AB  - Methoxyisopropanol and Methoxyisopropyl Acetate, commonly known as propylene
      glycol monomethyl ether (PGME) and propylene glycol monomethyl ether acetate
      (PGMEA), respectively, have fragrance, solvent, and viscosity-decreasing
      functions in cosmetics, although only Methoxyisopropanol is in current use at
      concentrations ranging from 4% to 35%. Methoxyisopropanol is easily absorbed into
      the bloodstream upon inhalation or ingestion. The acetate ester is readily
      metabolized to Methoxyisopropanol in the body, which is excreted unchanged in the
      expired breath or in the urine as free or conjugated Methoxyisopropanol, or as
      the primary metabolite propylene glycol. In acute oral toxicity studies, the
      LD(50) values of Methoxyisopropanol were 4.6 to 9.2 g/kg in rats, with similar
      low acute toxicity in other animal species. Inhalation exposures of rats, mice,
      and rabbits to 3000 ppm Methoxyisopropanol for 6 h per day for 9 days to 13 weeks
      produced increased relative liver weights, signs of central nervous system (CNS)
      depression, and in some cases, elevated serum alkaline phosphatase, alanine
      aminotransferase, or hepatocellular hypertrophy, but the kidneys were unaffected.
      The no observed adverse effect level (NOAEL) for 13-week inhalation exposures to
      Methoxyisopropanol was 1000 ppm in rats and rabbits. In a 90-day dermal exposure
      study using rabbits, 10 ml/kg undiluted Methoxyisopropanol produced narcosis and
      increased kidney weights and the NOAEL was 7.0 ml/kg. Chronic (2-year) daily
      inhalation exposures of rats and mice to 3000 ppm Methoxyisopropanol produced
      signs of liver toxicity (rats and mice) and some evidence of renal toxicity in
      rats. The only observation at 1000 ppm was dark foci of the liver in male rats.
      For female rats and male and female mice, the NOAEL of this chronic inhalation
      study was 1000 ppm Methoxyisopropanol. Methoxyisopropanol and Methoxyisopropyl
      Acetate were found to be nonirritating to slightly irritating and non-sensitizing
      in rabbit and guinea pig skin. Repeated applications of undiluted
      Methoxyisopropanol to the eyes of rabbits produced transient slight to moderate
      irritation. Pregnant rats exposed to 200 or 600 ppm Methoxyisopropanol by
      inhalation on gestation days 6 to 17 had no effects on maternal health or normal
      fetal development. Adult male rats exposed to these concentrations had no effects
      on the reproductive organs. Pregnant rats and rabbits exposed to 500 to 3000 ppm
      Methoxyisopropanol by inhalation during gestation had no significant embryotoxic
      or fetotoxic effects, althougth CNS depression and reduced body weight gain were
      observed in the 3000 ppm group. In a two-generation inhalation study using rats,
      continuous inhalation of 3000 ppm Methoxyisopropanol produced CNS depression,
      prolonged estrous cycles, reduced fertility indices, reduced pup weights and pup
      survival, and delayed sexual development, with a NOAEL for reproductive and
      developmental effects of 1000 ppm. In a continuous breeding protocol using mice,
      2.0% Methoxyisopropanol in drinking water produced reduced growth, reduced
      relative epididymis weight, reduced relative prostate weight, and increased liver
      weight (females only) in offspring, with a NOAEL at a 1% concentration. Exposure
      of mice or rats to 300 ppm to 3000 ppm Methoxyisopropanol by inhalation produced
      no signs of carcinogenicity. Methoxyisopropanol was negative for mutagenicity or
      genetic toxicity in the bacterial reverse mutation assay (<or= 5000
      microg/plate), the unscheduled DNA synthesis (UDS) assay (<or= 0.1 M), V79
      Chinese hamster lung assay (>100 mM), and in the Siberian hamster embryo assay
      (concentrations not reported). In other assays, 100 mM Methoxyisopropanol
      increased sister chromatid exchanges in V79 cells. In human inhalation exposure
      studies of 1 to 7 h duration, 50 to 75 ppm Methoxyisopropanol vapor had an
      objectionable odor; 150 ppm was slightly irritating to the eyes and throat; 250
      ppm produced eye irritation, lacrimation, blinking, rhinorrhea, and headache; 300
      ppm was mildly irritating to the eyes, nose, and throat; 750 ppm was extremely
      irritating; and 2050 ppm produced extreme discomfort with severe lacrimation,
      blepharospasm, and painful breathing. None of the concentrations tested impaired
      motor coordination or performance on neurological tests. The irritating effects
      subsided within 15 min to 24 h of removal from the inhalation chamber. The
      National Institute of Occupational Safety and Health (NIOSH) recommended an 8-h
      time-weighted average for occupational exposure of 100 ppm. A margin of safety of
      500 was determined, based on a calculated exposure from the normal use of nail
      polish remover products (100% absorption) and the NOAEL for reproductive
      toxicity. The absorption of Methoxyisopropanol through the nail is likely to be
      low, suggesting this margin of safety is conservative. Because Methoxyisopropanol
      is volatile, exposure by inhalation is possible, but the odor becomes
      objectionable at 50 to 75 ppm in air. The Cosmetic Ingredient Review (CIR) Expert
      Panel concluded that Methoxyisopropanol and Methoxyisopropyl Acetate are safe for
      use in nail care products in the practices of use and concentration as described
      in this safety assessment.

PMID- 18830863
TI  - Final report on the safety assessment of 3-methylamino-4-nitrophenoxyethanol as
      used in hair dyes.
AB  - 3-Methylamino-4-Nitrophenoxyethanol is a semipermanent (direct) hair colorant
      used in 21 hair dyes and colors at use concentrations up to 0.15%. When applied
      to human skin in vitro, 0.42% of the applied 3-Methylamino-4-Nitrophenoxyethanol
      was recovered in the receptor fluid. In an acute toxicity study using rats, 3
      Methylamino-4-Nitrophenoxyethanol at 1000 mg/kg resulted in hypoactivity,
      piloerection, dyspnea, and lateral recumbency in animals that later died. The
      surviving rats exhibited none of these signs. No abnormalities were found at
      necropsy. Subchronic toxicity tests using rats fed 25, 100, or 400 mg/kg day(-1)3
      Methylamino-4-Nitrophenoxyethanol for up to 93 days resulted in yellow urine and
      tails with all three dose levels and yellow fur occurred in the two high-dose
      groups. The no observed adverse effect level (NOAEL) for 3-Methyl-amino-4
      Nitrophenoxyethanol was 100 mg/kg day(- 1). Two percent 3-Methylamino-4
      Nitrophenoxyethanol was a slight ocular irritant but not a dermal irritant using
      rabbits and it was not a sensitizer using the murine local lymph node Assay.
      There were no embryotoxic or teratogenic effects observed in doses up to 750
      mg/kg day(-1) in rats; the NOAEL was defined as 100 mg/kg. 3-Methylamino-4
      Nitrophenoxyethanol was not genotoxic in in vitro assays including multiple
      strains of Salmonela typhimurium and Escherichia coli, Chinese Hamster ovary
      cells, and human lymphocyte cultures. No carcinogenicity studies were available,
      nor were any clinical tests reported. As reviewed by the Cosmetic Ingredient
      Review (CIR) Expert Panel, there are gaps in the data available for of 3
      Methylamino-4-Nitrophenoxyethanol. In particular, there is an absence of data
      from chronic animal studies. The Expert Panel considered that the low
      percutaneous absorption and that the available developmental toxicity data and
      the subchronic toxicity data, both of which resulted in relatively high NOAEL
      values, alleviate concern about the absence of chronic exposure data. In
      addition, several studies demonstrated that 3-Methylamino-4-Nitrophenoxyethanol
      is not genotoxic. Direct hair dyes, of which 3-Methylamino-4-Nitro-phenoxyethanol
      is one, although not the focus in all investigations, appear to have little
      evidence of an association with adverse events as reported in hair dye
      epidemiology studies. The lack of phototoxicity data was not considered to be a
      concern because this is a direct hair dye ingredient, which has little skin
      contact and residual color is attached to hair, not normally to skin. No human
      skin sensitization or irritation data were available. However, hair dyes
      containing 3-Methylamino-4-Nitrophenoxyethanol, as coal tar hair dye products,
      are exempt from the principal adulteration provision and from the color additive
      provisions in sections 601 and 706 of the Federal Food, Drug, and Cosmetic Act,
      when the label bears a caution statement and patch test instructions for
      determining whether the product causes skin irritation. The Expert Panel expects
      that following this procedure will prospectively identify individuals who would
      have an irritation/sensitization reaction and allow them to avoid significant
      exposures and concluded that 3-Methylamino-4-Nitrophenoxyethanol is safe as a
      cosmetic ingredient in the practices of use and use concentrations described in
      this safety report.

PMID- 18830864
TI  - Final report of the addendum to the safety assessment of n-butyl alcohol as used
      in cosmetics.
AB  - n-Butyl Alcohol is a primary aliphatic alcohol historically used as a solvent in
      nail care cosmetic products, but new concentration of use data indicate that it
      also is being used at low concentrations in eye makeup, personal hygiene, and
      shaving cosmetic products. n-Butyl Alcohol has been generally recognized as safe
      for use as a flavoring substance in food and appears on the 1982 Food and Drug
      Administration (FDA) list of inactive ingredients for approved prescription drug
      products. n-Butyl Alcohol can be absorbed through the skin, lungs, and
      gastrointestinal tract. n-Butyl Alcohol may be formed by hydrolysis of butyl
      acetate in the blood, but is rapidly oxidized. The single oral dose LD(50) of n
      Butyl Alcohol for rats was 0.79 to 4.36 g/kg. The dermal LD(50) for rabbits was
      4.2 g/kg. Inhalation toxicity studies in humans demonstrate sensory irritation of
      the upper respiratory tract, but only at levels above 3000 mg/m(3). Animal
      studies demonstrate intoxication, restlessness, ataxia, prostration, and
      narcosis. Exposures of rats to levels up to 4000 ppm failed to produce hearing
      defects. High concentrations of n-Butyl Alcohol vapors can be fatal. Ocular
      irritation was observed for n-Butyl alcohol at 0.005 ml of a 40% solution. The
      behavioral no-effect dose for n-Butyl Alcohol injected subcutaneously (s.c.) was
      120 mg/kg. Fetotoxicity has been demonstrated, but only at maternally toxic
      levels (1000 mg/kg). No significant behavioral or neurochemical effects were seen
      in offspring following either maternal or paternal exposure to 3000 or 6000 ppm.
      n-Butyl Alcohol was not mutagenic in Ames tests, did not induce sister-chromatid
      exchange or chromosome breakage in chick embryos or Chinese hamster ovary cells,
      did not induce micronuclei formation in V79 Chinese hamster cells, did not have
      any chromosome-damaging effects in a mouse micronucleus test, and did not impair
      chromosome distribution in the course of mitosis. Clinical testing of n-Butyl
      Alcohol for nonimmunological contact urticaria was negative in 105 subjects.
      Repeat-insult patch test (RIPT) studies of nail colors and enamels containing 3%
      n-Butyl Alcohol in one study produced reactions on challenge, but further study
      linked significant positive reactions to another solvent. In other RIPT studies,
      only minimal reactions were reported. A photopatch test demonstrated that a nail
      enamel containing 3% n-Butyl Alcohol resulted in no reactions. Workers complained
      of ocular irritation, disagreeable odor, slight headache and vertigo, slight
      irritation of nose and throat, and dermatitis of the fingers and hands when the
      air concentration of n-Butyl Alcohol was greater than 50 ppm, as compared to an
      odor threshold in air of 0.83 ppm. The available safety test data were considered
      adequate to support the safety of n-Butyl Alcohol in all cosmetic product
      categories in which it is currently used.

PMID- 18830865
TI  - Final report on the safety assessment of pentasodium pentetate and pentetic acid
      as used in cosmetics.
AB  - Pentasodium Pentetate and Pentetic Acid function as chelating agents in
      cosmetics. Pentasodium Pentetate is readily soluble in water, but the
      corresponding free acid is not. Pentasodium Pentetate is used in almost 400
      cosmetic products over a wide range of product categories, although it is mostly
      used in hair dyes and colors at use concentrations of 0.1% to 1.0%. Pentetic Acid
      is used in 150 cosmetic products, mostly in hair dyes and colors. Chelating
      agents are used in cosmetics to remove calcium and magnesium cations, which
      impede foaming and cleansing performance and which can cause a haze in clear
      liquids. The acute oral LD(50) of Pentasodium Pentetate in rats was > 5 g/kg. The
      acute dermal LD(50) of Pentapotassium Pentetate using rats was reported to be > 2
      g/kg. The intraperitonal LD(50) of Pentetic Acid was reported to be 585 mg/kg.
      Short-term studies of the calcium and sodium salts of Pentetic Acid in male mice
      demonstrated no dose-related toxicity over the dose range of 10, 100, and 250
      mg/kg. In a 4-week dermal toxicity study, daily topical application of 0.05%
      Pentasodium Pentetate to shaved and abraded rabbit skin produced moderate
      erythema after the first week and throughout the study, but no systemic toxicity.
      Pentasodium Pentetate or Pentapotassium Pentetate applied to intact albino rabbit
      skin were not irritating. A 40% solution of Pentapotassium Pentetate was not
      sensitizing in a guinea pig maximization test. The no observed adverse effect
      level (NOAEL) for rats given 40% Pentapotassium Pentetate by oral gavage was
      reported to be 83 mg/kg day(-1). Subchronic inhalation evaluation of a bath
      freshener containing 0.05% or 0.09% Pentasodium Pentetate using albino rats
      determined that there was no cumulative systemic toxicity attributable to the
      ingredient at either concentration. The no observed effect level (NOEL) for
      maternal toxicity in pregnant rats was 400 mg/kg body weight and for fetal
      toxicity was 100 mg/kg body weight. Another reproductive toxicity study evaluated
      Pentetic Acid-Zn with and without sodium chloride in pregnant C57/B1 Dougherty
      mice. No toxicity was found without added sodium chloride. Pentapotassium
      Pentetate was not mutagenic in an Ames test, with or without metabolic
      activation. The same material tested in Chinese hamster ovary cells was not
      clastogenic. Calcium Pentetate at 1.351 microg/ml produced a statistically
      significant increase in the number of sister-chromatid exchanges. Pentasodium
      Pentetate is nonirritating to moderately irritating, but not a sensitizer in
      clinical tests. A human comedogenicity (acne promotion) test using Pentasodium
      Pentetate found no effect. Although data are lacking on the dermal penetration of
      these two ingredients, other chelating agents such as EDTA do not penetrate the
      skin, so it is likely that Pentasodium Pentetate and Pentetic Acid also would not
      penetrate. The high water solubility of Pentasodium Pentetate and the low water
      solubility of Pentetic Acid also support that their dermal penetration will be
      low. Other chelating agents, including EDTA and its salts, have been determined
      to be safe in the current practices of use in cosmetics. Meta-, Tri-, and
      Hexametaphosphate salts are chelating agents determined to be safe in the current
      practices of use in cosmetics. Metasilicate salts were found to be safe as
      chelating agents in cosmetics when formulated to avoid irritation. Overall, these
      data were considered sufficient to support the safety of Pentesodium Pentetate
      and Pentetic Acid as used in cosmetics.

PMID- 18830866
TI  - Safety assessment of poloxamers 101, 105, 108, 122, 123, 124, 181, 182, 183, 184,
      185, 188, 212, 215, 217, 231, 234, 235, 237, 238, 282, 284, 288, 331, 333, 334,
      335, 338, 401, 402, 403, and 407, poloxamer 105 benzoate, and poloxamer 182
      dibenzoate as used in cosmetics.
AB  - Poloxamers are polyoxyethlyene, polyoxypropylene block polymers. The impurities
      of commercial grade Poloxamer 188, as an example, include low-molecular-weight
      substances (aldehydes and both formic and acetic acids), as well as 1,4-dioxane
      and residual ethylene oxide and propylene oxide. Most Poloxamers function in
      cosmetics as surfactants, emulsifying agents, cleansing agents, and/or
      solubilizing agents, and are used in 141 cosmetic products at concentrations from
      0.005% to 20%. Poloxamers injected intravenously in animals are rapidly excreted
      in the urine, with some accumulation in lung, liver, brain, and kidney tissue. In
      humans, the plasma concentration of Poloxamer 188 (given intravenously) reached a
      maximum at 1 h, then reached a steady state. Poloxamers generally were
      ineffective in wound healing, but were effective in reducing postsurgical
      adhesions in several test systems. Poloxamers can cause hypercholesterolemia and
      hypertriglyceridemia in animals, but overall, they are relatively nontoxic to
      animals, with LD(50) values reported from 5 to 34.6 g/kg. Short-term intravenous
      doses up to 4 g/kg of Poloxamer 108 produced no change in body weights, but did
      result in diffuse hepatocellular vacuolization, renal tubular dilation in
      kidneys, and dose-dependent vacuolization of epithelial cells in the proximal
      convoluted tubules. A short-term inhalation toxicity study of Poloxamer 101 at 97
      mg/m(3) identified slight alveolitis after 2 weeks of exposure, which subsided in
      the 2-week postexposure observation period. A short-term dermal toxicity study of
      Poloxamer 184 in rabbits at doses up to 1000 mg/kg produced slight erythema and
      slight intradermal inflammatory response on histological examination, but no dose
      dependent body weight, hematology, blood chemistry, or organ weight changes. A 6
      month feeding study in rats and dogs of Poloxamer 188 at exposures up to 5% in
      the diet produced no adverse effects. Likewise, Poloxamer 331 (tested up to 0.5
      g/kg day(-1)), Poloxamer 235 (tested up to 1.0 g/kg day(-1)), and Poloxamer 338
      (at 0.2 or 1.0 g/kg day(-1)) produced no adverse effects in dogs. Poloxamer 338
      (at 5.0 g/kg day(-1)) produced slight transient diarrhea in dogs. Poloxamer 188
      at levels up to 7.5% in diet given to rats in a 2-year feeding study produced
      diarrhea at 5% and 7.5% levels, a small decrease in growth at the 7.5% level, but
      no change in survival. Doses up to 0.5 mg/kg day(-1) for 2 years using rats
      produced yellow discoloration of the serum, high serum alkaline phosphatase
      activity, and elevated serum glutamicpyruvic transaminase and glutamic-oxalacetic
      transaminase activities. Poloxamers are minimal ocular irritants, but are not
      dermal irritants or sensitizers in animals. Data on reproductive and
      developmental toxicity of Poloxamers were not found. An Ames test did not
      identify any mutagenic activity of Poloxamer 407, with or without metabolic
      activation. Several studies have suggested anticarcinogenic effects of
      Poloxamers. Poloxamers appear to increase the sensitivity to anticancer drugs of
      multidrug-resistant cancer cells. In clinical testing, Poloxamer 188 increased
      the hydration of feces when used in combination with a bulk laxative treatment.
      Compared to controls, one study of angioplasty patients receiving Poloxamer 188
      found a reduced myocardial infarct size and a reduced incidence of reinfarction,
      with no evidence of toxicity, but two other studies found no effect. Poloxamer
      188 given to patients suffering from sickle cell disease had decreased pain and
      decreased hospitilization, compared to controls. Clinical tests of dermal
      irritation and sensitization were uniformly negative. The Cosmetic Ingredient
      Review (CIR) Expert Panel stressed that the cosmetic industry should continue to
      use the necessary purification procedures to keep the levels below established
      limits for ethylene oxide, propylene oxide, and 1,4-dioxane. The Panel did note
      the absence of reproductive and developmental toxicity data, but, based on
      molecular weight and solubility, there should be little skin penetration and any
      penetration of the skin should be slow. Also, the available data demonstrate that
      Poloxamers that are introduced into the body via routes other than dermal
      exposure have a rapid clearance from the body, suggesting that there would be no
      risk of reproductive and/or developmental toxicity. Overall, the available data
      do not suggest any concern about carcinogenesis. Although there are gaps in
      knowledge about product use, the overall information available on the types of
      products in which these ingredients are used, and at what concentration,
      indicates a pattern of use. Based on these safety test data and the information
      that the manufacturing process can be controlled to limit unwanted impurities,
      the Panel concluded that these Poloxamers are safe as used.

PMID- 18830867
TI  - Treatment of port wine stains with pulsed dye laser in patients with systemic
      lupus erythematosus: practical considerations and complications.
AB  - There is a paucity of clinical information on the treatment of port wine stains
      (PWS) with pulse dye lasers (PDL) in patients with connective tissue diseases.
      Systemic lupus (SLE) is characterized by increased skin fragility and the
      potential for pigmentary alterations. Additionally, medications used to treat SLE
      may alter patient responses to laser therapy. We describe two complications,
      tense blisters and hypopigmentation, after PDL treatment of PWS in SLE, and
      discuss the current knowledge on the use of PDL in patients with lupus.

PMID- 18830868
TI  - Long-pulsed neodymium:yttrium-aluminum-garnet laser treatment for hypertrophic
      port-wine stains on the lips.
AB  - Pulsed dye laser (PDL) treatment of hypertrophic port-wine stains (PWSs) on the
      lips has demonstrated poor efficacy and a potential risk of dyspigmentation. PDL
      resistant hypertrophic PWS may require treatment with deeper penetrating lasers
      such as a 1064-nm neodymium:yttrium-aluminum-garnet (Nd:YAG) laser. The objective
      of this clinical study was to evaluate the efficacy and safety of a Nd:YAG laser
      for the treatment of hypertrophic PWSs on the lips. Ten patients (four were male
      and six were female) with hypertrophic PWSs on the lips were recruited in this
      study. Eight patients showed good to excellent improvement without complications.
      In conclusion, the Nd:YAG laser is safe and effective for treating hypertrophic
      PWSs on the lips.

PMID- 18830869
TI  - Intravenous vitamin C in the treatment of post-laser hyperpigmentation for
      melasma: a short report.
AB  - Melasma is difficult to treat. Vitamin C, topical and by iontophoresis, has been
      shown to be useful. When lasers are used, there is a significant incidence of
      post-laser hyperpigmentation. There is no single established treatment for the
      latter. The case history of a 51-year-old Chinese woman is presented. Intravenous
      vitamin C appears to be useful in treating this complication.

PMID- 18830870
TI  - Hair removal on dark-skinned patients with pneumatic skin flattening (PSF) and a
      high-energy Nd:YAG laser.
AB  - BACKGROUND: Permanent laser hair removal is normally performed with high-energy
      densities and associated with acute pain. Pneumatic skin flattening (PSF) is a
      new technology, which helps to control the pain during laser aesthetic
      treatments. Based on the gate theory of pain transmission, it activates tactile
      and pressure skin receptors just before the laser shot to naturally block the
      transmission of pain to the brain while the laser is activated. OBJECTIVE: To
      test the safety, pain reduction, as well as the efficacy of PSF in hair removal
      on patients with dark skin (mainly skin types IV, V and VI) with a high-energy
      Nd:YAG laser and without skin chilling. METHODS: Patients were treated for hair
      removal with a 1064-nm laser (GentleYAG, Candela) at energy densities of 40-44
      J/cm(2). Each patient was treated on both axillae: PSF on one side and without
      PSF (but with a chiller) on control sites. Pain was evaluated on a 1-10 scale.
      Hair re-growth was counted after 12 weeks. A second treatment was delivered at
      that time for additional evaluation of pain and further efficacy evaluation. Post
      treatment erythema and adverse effects were also noted. RESULTS: Pain reduction
      was demonstrated in all 28 patients: the average was 2.6 with PSF and 4.5 without
      PSF. Hair removal efficacy with and without PSF was identical: 78-79% hair
      reduction after 12 weeks (standard deviation 14% and 10% respectively, t-test:
      0.78). There were no cases of adverse effects and post-treatment erythema was
      consistently lower with PSF. All patients preferred PSF over non-PSF treatment.
      CONCLUSION: The PSF technology considerably reduces pain in hair removal with
      high-energy Nd:YAG lasers on dark skins without side effects, while preserving
      efficacy. Analgesic creams and skin chilling are not required.

PMID- 18830871
TI  - Angiokeratomas of Fabry successfully treated with intense pulsed light.
AB  - Fabry disease (FD) is a rare X-linked lysosomal storage disorder resulting from
      the deficient activity of the enzyme alpha-galactosidase A. Angiokeratomas (AKs)
      are a frequent manifestation of this disease. They usually become apparent during
      childhood and can cause important cosmetic disability. Current treatment of this
      feature in the setting of FD has been mainly based on the application of laser
      systems, namely the argon laser, the variable pulse width 532-nm Nd:YAG laser,
      the 578-nm copper vapor laser and the flashlamp-pumped pulsed dye laser. We
      report the case of a 31-year-old Caucasian woman with a clinical and molecular
      (GLA p.R118C) diagnosis of FD, presenting multiple AKs scattered over the
      buttocks and thighs. She was treated with 10 sessions of intense pulsed light
      (IPL), with a 4-8-week interval between them. An almost complete clearance of the
      lesions was obtained, with no scars or significant complaints. No recurrence
      occurred during a 12-month follow-up period. The IPL source can be considered a
      suitable, effective and safe treatment modality for these cutaneous lesions that
      typically affect patients with FD, with no need for local anesthesia and with
      very satisfactory cosmetic results. To our best knowledge, there are no reports
      in the literature of Fabry's AKs treated with IPL.

PMID- 18830872
TI  - Insights through AM1 calculations into the structural requirement of N
      hydroxythiosemicarbazone analogs as anti-tubercular agents.
AB  - Fujita-Ban, Hansch substituent constants, topological descriptors and
      conformational dependent descriptors were explored for quantification of anti
      tubercular activity of N-hydroxythiosemicarbazone analogs. All the approaches
      gave statistically sound model which accounts for more than 88% of the explain
      variance against anti-tubercular activity except Fujita-Ban (approximately 75%).
      Fujita-Ban & Hansch approaches having certain limitation, however, another
      approache showed their significant role in explaining activity of the modified
      scaffolds. QSAR study of N-Hydroxythiosemicarbazone analogs furnished some
      important structural insights i.e., the R position is more prone for improving
      inhibitory activity and the R(1) position play a decisive role in the ionic
      interaction of the ligand with macromolecules. On the basis of findings, N
      hydroxythiosemicarbazones interaction model with macromolecule of M. Tuberculosis
      has been proposed. These interactions might be helpful in further development of
      potent anti-tubercular agents.

PMID- 18830873
TI  - QSAR studies for the inhibition of the transmembrane carbonic anhydrase isozyme
      XIV with sulfonamides using PRECLAV software.
AB  - QSAR studies for the inhibition of isozyme XIV of human carbonic anhydrase (CA,
      EC 4.2.1.1) by a series of sulfonamides including clinically used derivatives
      (acetazolamide, methazolamide, ethoxzolamide, dichlorophenamide, dorzolamide,
      brinzolamide, benzolamide, and zonisamide) are presented. Statistical
      calculations done using the PRECLAV program, for the correlation between the
      observed inhibition values and the calculated ones were good (s = 0.2416, r(2) =
      0.9259, F = 75.0196, [image omitted] ). The obtained results by using PRECLAV
      descriptors have been compared with those where the descriptors have been
      calculated with HYPERCHEM. The obtained QSAR equations pointed out the fact that
      the CA inhibitory activity decreased for unsubstituted (at the organic scaffold)
      aromatic/heteroaromatic sulfonamides, but was favored by the presence of alkyl
      groups substituting the scaffold, which led to a higher internal topological
      diversity, as well as by the presence of condensed aromatic rings in the
      structure of these enzyme inhibitors.

PMID- 18830874
TI  - Inhibition of human muscle-specific enolase by methylglyoxal and irreversible
      formation of advanced glycation end products.
AB  - Methylglyoxal (MG) was studied as an inhibitor and effective glycating factor of
      human muscle-specific enolase. The inhibition was carried out by the use of a
      preincubation procedure in the absence of substrate. Experiments were performed
      in anionic and cationic buffers and showed that inhibition of enolase by
      methylglyoxal and formation of enolase-derived glycation products arose more
      effectively in slight alkaline conditions and in the presence of inorganic
      phosphate. Incubation of 15 micromolar solutions of the enzyme with 2 mM, 3.1 mM
      and 4.34 mM MG in 100 mM phosphate buffer pH 7.4 for 3 h caused the loss a 32%,
      55% and 82% of initial specific activity, respectively. The effect of MG on
      catalytic properties of enolase was investigated. The enzyme changed the K(M)
      value for glycolytic substrate 2-phospho-D-glycerate (2-PGA) from 0.2 mM for
      native enzyme to 0.66 mM in the presence of MG. The affinity of enolase for
      gluconeogenic substrate phosphoenolpyruvate altered after preincubation with MG
      in the same manner, but less intensively. MG has no effect on V(max) and optimal
      pH values. Incubation of enolase with MG for 0-48 h generated high molecular
      weight protein derivatives. Advanced glycation end products (AGEs) were resistant
      to proteolytic degradation by trypsin. Magnesium ions enhanced the enzyme
      inactivation by MG and facilitated AGEs formation. However, the protection for
      this inhibition in the presence of 2-PGA as glycolytic substrate was observed and
      AGEs were less effectively formed under these conditions.

PMID- 18830875
TI  - Inhibitory effects of Cefazolin and Cefodizime on the activity of mushroom
      tyrosinase.
AB  - Tyrosinase (EC 1.14.18.1) catalyzes both the hydroxylation of tyrosine into o
      diphenols and the oxidation of o-diphenols into o-quinones that form brown or
      black pigments. In the present paper, the effects of Cefazolin and Cefodizime on
      the activity of mushroom tyrosniase have been studied. The results showed that
      the Cephalosporin antibacterial drugs (Cefazolin and Cefodizime) could inhibit
      both monophenolase activity and diphenolase activity of the enzyme. For the
      monophenolase activity, Both Cefazolin and Cefodizime could lengthen the lag time
      and decrease the steady-state activities, and the IC(50) values were estimated as
      7.0 mM and 0.13 mM for monophenolase activity, respectively. For the diphenolase
      activity, the inhibitory capacity of Cefodizime was obviously stronger than that
      of Cefazolin, and the IC(50) values were estimated as 0.02 mM and 0.21 mM,
      respectively. Kinetic analyses showed that inhibition by both compounds was
      reversible and their mechanisms were competitive and mixed-type, respectively.
      Their inhibition constants were also determined and compared. The research may
      offer a lead for designing and synthesizing novel and effective tyrosinase
      inhibitors and also under the application field of Cephalosporins.

PMID- 18830876
TI  - Cytotoxic activity of 4'-hydroxychalcone derivatives against Jurkat cells and
      their effects on mammalian DNA topoisomerase I.
AB  - Chalcones (1,3-diaryl-2-propen-1-ones) are alpha, beta-unsaturated ketones with
      cytotoxic and anticancer properties. Several reports have shown that compounds
      with cytotoxic properties may also interfere with DNA topoisomerase functions.
      Five derivatives of 4'-hydroxychalcones were examined for cytotoxicity against
      transformed human T (Jurkat) cells as well as plasmid supercoil relaxation
      experiments using mammalian DNA topoisomerase I. The compounds were 3-phenyl-1
      (4'-hydroxyphenyl)-2-propen-1-one (I), 3-(p-methylphenyl)-1-(4'-hydroxyphenyl)-2
      propen-1-one (II), 3-(p-methoxyphenyl)-1-(4'-hydroxyphenyl)-2-propen-1-one (III),
      3-(p-chlorophenyl)-1-(4'-hydroxyphenyl)-2-propen-1-one (IV), and 3-(2- thienyl)-1
      (4'-hydroxyphenyl)-2-propen-1-one (V). The order of the cytotoxicity of the
      compounds was; IV > III > II > I > V. Compound IV, had the highest Hammett and
      log P values (0.23 and 4.21, respectively) and exerted both highest cytotoxicity
      and strongest DNA topoisomerase I inhibition. Compounds I and II gave moderate
      interference with the DNA topoisomerase I while III & V did not interfere with
      the enzyme.

PMID- 18830877
TI  - Umbelliferone aminoalkyl derivatives as inhibitors of human oxidosqualene
      lanosterol cyclase.
AB  - Human and murine lanosterol synthases (EC 5.4.99.7) were studied as targets of a
      series of umbelliferone aminoalkyl derivatives previously tested as inhibitors of
      oxidosqualene cyclases from other eukaryotes. Tests were carried out on cell
      cultures of human keratinocytes and mouse 3T3 fibroblasts incubated with
      radiolabeled acetate, and on homogenates prepared from yeast cells expressing
      human lanosterol synthase, incubated with radiolabeled oxidosqualene. In cell
      cultures of both human keratinocytes and mouse 3T3 fibroblasts, the observed
      inhibition of cholesterol biosynthesis was selective for oxidosqualene cyclase.
      The most active compounds bear an allylmethylamino chain in position-7 of the
      coumarin ring. The inhibition was critically dependent on the position and length
      of the inhibitor side chain, as well as on the type of aminoalkyl group inserted
      at the end of the same chain. Molecular docking analyses, carried out to clarify
      details of inhibitors/enzyme interactions, proved useful to explain the observed
      differences in inhibitory activities.

PMID- 18830878
TI  - Ca2+/calmodulin-dependent protein kinase II mediates apoptosis of P19 cells
      expressing human tau during neural differentiation with retinoic acid treatment.
AB  - The involvement of tau phosphorylation in apoptosis resembling Alzheimer's
      disease (AD) was investigated using a cell model of P19 cells stably expressing
      human tau441 (tau/P19 cells). Apoptotic cell death was observed specifically in
      tau/P19 cells during neural differentiation with retinoic acid (RA) treatment. A
      CaM kinase II inhibitor, KN-93, protected tau/P19 cells from apoptosis, although
      it stimulated the cell death of wild-type P19 cells (wt/P19 cells). W-7 and
      calmidazolium, calmodulin antagonists, also specifically inhibited the apoptosis
      of tau/P19 cells. LiCl, an inhibitor of glycogen synthase 3, a tau kinase, was
      effective in protecting tau/P19 cells from apoptosis, but the protective effect
      was less than that of CaM kinase II inhibitor and calmodulin antagonists. Tau in
      the nuclei of tau/P19 cells was phosphorylated at the sites for CaM kinase II
      detected by an antibody recognizing a phosphorylated form of tau. These results
      indicated that CaM kinase II was involved in the apoptosis of tau/P19 cells
      induced by RA treatment.

PMID- 18830879
TI  - A facile solid-state synthesis and in vitro antimicrobial activities of some 2,6
      diarylpiperidin/tetrahydrothiopyran and tetrahydropyran-4-one oximes.
AB  - Some 2,6-diarylpiperidin/tetrahydrothiopyran/tetrahydropyran-4-one oximes were
      synthesized in dry media under microwave irradiation and were evaluated for their
      in vitro antibacterial activity against clinically isolated bacterial strains
      i.e. S.aureus, beta-H.Streptococcus, E.coli, P.aeruginosa, S.typhii and in vitro
      antifungal activities against fungal strains i.e. C.albicans, Rhizopus, A.niger
      and A.flavus. Structure-activity relationships for the synthesized compounds
      showed that compounds 12 and 15 exerted excellent antibacterial activity against
      all the tested bacterial strains except 15 against S.aureus and beta
      H.streptococcus. Against C.albicans and A.flavus, compound 15 exerted potent
      antifungal activities while against Rhizopus, compound 16 showed promising
      activity.

PMID- 18830880
TI  - Antioxidant and hepatoprotective potential of Aegle marmelos Correa. against CCl4
      induced oxidative stress and early tumor events.
AB  - The antioxidant properties and inhibitory effect on early tumor promoter markers
      of A. marmelos (25 and 50 mg/Kg b. wt. orally) have been evaluated. Male Wistar
      rats were pre-treated for seven consecutive days with A. marmelos prior to CCl4
      (1 mL Kg(- 1) body weight p. o., in corn oil [1:1 v/v]) treatment. Pre-treatment
      with A. marmelos suppressed lipid peroxidation (LPO), xanthine oxidase (XO) and
      release of serum toxicity marker enzymes viz, SGOT, LDH, SGPT dose-dependently
      and significantly (p < 0.001). Hepatic antioxidant status viz, reduced
      glutathione (GSH), glutathione reductase (GR), glutathione peroxidase (GPx),
      quinone reductase (QR), catalase (CAT) were concomitantly restored in A. marmelos
      treated groups (p < 0.001). In addition, A. marmelos pretreatment also prevented
      the CCl4-enhanced ornithine decarboxylase (ODC) and hepatic DNA synthesis
      significantly (p < 0.001). In conclusion, carbon tetrachloride-induced liver
      toxicity was strikingly attenuated by A. marmelos treatment and the study gives
      some insight into the mechanisms involved in diminution of free radical
      generating toxicants and enhancement of the antioxidant armory, hence preventing
      further tissue damage, injury and hyperproliferation. Thus, these findings
      indicate that A. marmelos attenuates CCl4-mediated hepatic oxidative stress,
      toxicity, tumor promotion and subsequent cell proliferation response in Wistar
      rats.

PMID- 18830881
TI  - Employment of pumpkin (Cucumis melo) urease entrapped in alginate beads for
      quantitation of cadmium in aqueous media.
AB  - The potential of employment of free as well as alginate-immobilized urease for
      the quantitation of cadmium (Cd(2+)) was explored. Urease from the seeds of
      pumpkin (Cucumis melo) was purified to apparent homogeneity by heat treatment at
      48 +/- 0.1 degrees C and gel filtration through Sephadex G-200. The purified
      enzyme exhibited a single band on native PAGE under coomassie brilliant blue and
      silver staining. The enzyme entrapped in 3.5% alginate beads (with 86%
      immobilization) exhibited no leaching over a period of 15 days at 4 degrees C.
      Urease-catalyzed urea hydrolysis by both soluble and immobilized enzyme revealed
      a dependence on the inhibitor concentration. The inhibition caused by Cd(2+) was
      non-competitive and the interaction of Cd(2+) with the enzyme was irreversible as
      the activity could not be restored by dialysis. The time-dependent inhibition
      both in the presence and in absence of substrate revealed a biphasic inhibition
      of the activity. The significance of the results is discussed.

PMID- 18830882
TI  - Inhibition of rat liver cathepsins B and L by the peptide aldehyde
      benzyloxycarbonyl-leucyl-leucyl-leucinal and its analogues.
AB  - Cathepsins B and L belong to the papain superfamily of cysteine proteases and
      play important roles in various physiological and pathological processes. In the
      course of studies on their inhibitors, we examined the inhibitory effects of the
      peptide aldehyde benzyloxycarbonyl-leucyl-leucyl-leucinal (ZLLLal) and its
      analogues. As a result, rat liver cathepsins B and L were shown to be strongly
      inhibited by them. The concentration required for 50% inhibition (IC(50)) by
      ZLLLal was 88 nM for cathepsin B and 163 nM for cathepsin L. Moreover, various
      analogues of ZLLLal, including 2-furancarbonyl-, nicotinyl-, isonicotinyl- and 4
      morpholinylsuccinyl-LLLals, and some acetyl-Pro (AcP)-containing analogues,
      AcPLLLal and AcPPLLLal, were shown to inhibit both enzymes more strongly than
      ZLLLal. Among them, isonicotinyl-LLLal was most inhibitory against both
      cathepsins B (IC(50), 12 nM) and L (IC(50), 20 nM). Several of these inhibitors
      were indicated to be somewhat more soluble in aqueous media than ZLLLal.

PMID- 18830883
TI  - In vitro antioxidant activity of silymarin.
AB  - Silymarin, a known standardized extract obtained from seeds of Silybum marianum
      is widely used in treatment of several diseases of varying origin. In the present
      paper, we clarified the antioxidant activity of silymarin by employing various in
      vitro antioxidant assay such as 1,1-diphenyl-2-picryl-hydrazyl free radical
      (DPPH(.)) scavenging, 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid)
      (ABTS) radical scavenging activity, total antioxidant activity determination by
      ferric thiocyanate, total reducing ability determination by Fe3+ - Fe2+
      transformation method and Cuprac assay, superoxide anion radical scavenging by
      riboflavin/methionine/illuminate system, hydrogen peroxide scavenging and ferrous
      ions (Fe2+) chelating activities. Silymarin inhibited 82.7% lipid peroxidation of
      linoleic acid emulsion at 30 microg/mL concentration; butylated hydroxyanisole
      (BHA), butylated hydroxytoluene (BHT), alpha-tocopherol and trolox indicated
      inhibition of 83.3, 82.1, 68.1 and 81.3% on peroxidation of linoleic acid
      emulsion at the same concentration, respectively. In addition, silymarin had an
      effective DPPH(.) scavenging, ABTS(.)+ scavenging, superoxide anion radical
      scavenging, hydrogen peroxide scavenging, ferric ions (Fe3+) reducing power by
      Fe3+-Fe2+ transformation, cupric ions (Cu2+) reducing ability by Cuprac method,
      and ferrous ions (Fe2+) chelating activities. Also, BHA, BHT, alpha-tocopherol
      and trolox, were used as the reference antioxidant and radical scavenger
      compounds. Moreover, this study, which clarifies antioxidant mechanism of
      silymarin, brings new information on the antioxidant properties of silymarin.
      According to the present study, silymarin had effective in vitro antioxidant and
      radical scavenging activity. It could be used in the pharmacological and food
      industry because of its antioxidant properties.

PMID- 18830884
TI  - Design, synthesis and in vitro microbiological evaluation of 6,6-dimethyl-7,9
      diaryl-1,2,4,8-tetraazaspiro[4.5]decan-3-thiones--a new series of 'tailor-made'
      compounds.
AB  - Some novel 'tailor-made' compounds, 6,6-dimethyl-7,9-diaryl-1,2,4,8
      tetraazaspiro[4.5]decan-3-thiones 23-27 have been studied for their in vitro
      antibacterial activity against Staphylococcus aureus, beta-Heamolytic
      streptococcus, Vibreo cholerae, Salmonella typhii, Shigella felxneri, Escherichia
      coli, Klebsiella pneumonia, Pseudomonas aeruginosa and anti-fungal activity
      against Aspergillus flavus, Mucor, Rhizopus and Microsporum gypsuem. Compounds 24
      and 25 exerted potent antibacterial activity against S. aureus, beta-H.
      streptococcus, E. coli and P. aeruginosa whereas all compounds 23-27 exerted
      strong in vitro antifungal activity against A. flavus, Mucor and Rhizopus.

PMID- 18830885
TI  - Synthesis and biological evaluation of novel flavonoid derivatives as dual
      binding acetylcholinesterase inhibitors.
AB  - A new series of flavonoid derivatives have been designed, synthesised and
      evaluated as acetylcholinesterase inhibitors that could bind simultaneously to
      the peripheral and catalytic sites of the enzyme. Among them, fifteen derivatives
      were found to inhibit the enzyme in the micromolar range and isoflavone
      derivatives possessed more potent inhibitory activity than other flavonoid
      derivatives. The best compound 9a had its inhibitory activity (IC(50) = 0.093
      microM) in the same range as the reference compound, donepezil (IC(50) = 0.025
      microM). Preliminary structure-activity relationships and a molecular modeling
      study for 9a have revealed that the isoflavone moiety plays a key role in the
      interaction of this series of derivatives with AChE by acting as an anchor in its
      peripheral anionic site.

PMID- 18830886
TI  - (Xeno)estrogen regulation of food allergy.
AB  - Food allergy and other types of allergies are becoming epidemic in both the
      developed and developing countries. A large amount of information is available in
      literature that (xeno)estrogens can regulate the immune response in general, and
      the development of allergy in particular; however, the effect of (xeno)estrogens
      on food allergy is basically unknown. With increasing use of xenobiotics
      worldwide, chemicals with estrogenic activity have been accumulating in our
      environment. This review has summarized the current literature relating to the
      topic (xeno)estrogen regulation of food allergy. The effect of (xeno)estrogens on
      enterocytes, proteases for protein hydrolysis, dendritic cells and T-regulatory
      cells in the gastrointestinal tract has been discussed. Finally, considering the
      current confusion in literature regarding the effect of phytoestrogen genistein
      on the immune system, a brief discussion has been included for its effect on
      T(H)1-T(H)2 polarization, and possibly food allergy in its relation to windows of
      exposure. Sufficient evidences exist to support the notion that (xeno)estrogens
      can regulate food allergy, with the developmental periods more sensitive. Further
      clinical and animal studies are needed to determine the causal relationship
      between the exposure of (xeno)estrogens and incidence of food allergy, and the
      underlying mechanisms.

PMID- 18830887
TI  - Use of an ex vivo local lymph node assay to assess contact hypersensitivity
      potential.
AB  - The local lymph node assay (LLNA) is used to assess the contact hypersensitivity
      potential of compounds. In the standard assay, mice are treated topically with
      test compound to the dorsum of both ears on Days 1-3. The induction of a
      hypersensitivity response is assessed on Day 6 by injecting [(3)H]-thymidine into
      a tail vein and measuring thymidine incorporation into DNA of lymph node cells
      draining the ears. The ex vivo LLNA is conducted similarly except lymphocyte
      proliferation is assessed after in vitro incubation of lymph node cells with
      [(3)H]-thymidine, which significantly reduces the amount of radioactive waste.
      The current study tested the use of this approach for hazard assessment of
      contact hypersensitivity and to estimate allergenic potency. Female BALB/c mice
      were treated on Days 1-3 with two nonsensitizers (4' -methoxyacetophenone,
      diethyl phthalate), three weak sensitizers (hydroxycitronellal, eugenol, citral),
      one weak-to-moderate sensitizer (hexylcinnamic aldehyde), two moderate
      sensitizers (isoeugenol, phenyl benzoate), and one strong sensitizer
      (dinitrochlorobenzene). On Day 6, isolated lymph node cells were incubated
      overnight with [(3)H]-thymidine and thymidine incorporation was measured by
      liquid scintillation spectrophotometry. The ex vivo LLNA accurately distinguished
      the contact sensitizers from the nonsensitizing chemicals, and correctly ranked
      the relative potency of the compounds tested. The EC3 values, i.e., the effective
      concentration of test substance needed to induce a stimulation index of 3, were
      as follows: 4' -methoxyacetophenone (> 50%), diethyl phthalate (> 50%),
      hydroxycitronellal (20.4%), eugenol (13.6%), citral (8.9%), isoeugenol (3.8%),
      hexylcinnamic aldehyde (2.7%), phenyl benzoate (2%), and dinitrochlorobenzene
      (0.02%). In addition, low inter-animal and inter-experiment variability was seen
      with 25% hexyl-cinnamic aldehyde (assay positive control). The results of the ex
      vivo LLNA in the current study were consistent with published reports using the
      standard LLNA and provided further evidence that supports the use of this
      alternative approach to assess the skin sensitization potential of test
      compounds.

PMID- 18830888
TI  - Enhancement of natural killer cell activity in vitro against human tumor cells by
      some plants from Jordan.
AB  - The effect of different concentrations (0, 0.01, 0.1, and 0.5 mg/ml) of plant
      aqueous extracts on the anti-tumor activity of natural killer (NK) cells isolated
      from human blood was examined. Plant extracts induced significant enhancement of
      (26.6-67.7%) of NK cell activity against K562 tumor cells. This increase in NK
      cell cytotoxicity was found to be due to the enhancement of NK cell production of
      interferon-gamma (87-337%), and on tumor necrosis factor-alpha (60-200%).
      Furthermore, the release of both granzyme A and N-acetyl-beta-D-glucosaminidase
      was increased significantly when compared with controls. Activation of granzyme A
      and N-acetyl-beta-D-glucosaminidase was clearly observed ranging from 24.2-106.4%
      to 26.8-110.7%, respectively. Lastly, in the absence of IL-2, plant extracts
      caused a significant increase in NK-cell-induced cytotoxicity (256%) against K562
      tumor cells, and in the presence of IL-2 stimulated cells plant extracts caused
      an increase in NK cell-cytotoxicity (112%).

PMID- 18830889
TI  - Enhancement of saporin toxicity against U937 cells by Gypsophila saponins.
AB  - Saporin, a type I ribosome-inactivating protein (RIP), removes an adenine residue
      from the 28S ribosomal RNA as part of a process that leads to inhibition of
      protein synthesis. As a result, saporin has been shown to exert a strong toxicity
      in the immune system against macrophages. However, studies have shown that
      macrophage-like U937 cells are fully resistant against low concentrations of
      unmodified and his-tagged saporin solutions (6 pM) that normally kill macrophages
      and APC. In the studies reported here, we noted that with these cells, these RIP
      solutions only became highly cytotoxic when they were used in a combined
      treatment with Gypsophila saponins. We determined that this cytotoxicity was the
      result of an induction of apoptosis triggered by the now-internalized saporin
      molecules that had previously remained outside of these cells. The results here
      indicate that the Gypsophila saponins induce, in some manner yet to be fully
      defined, a stimulation of the endocytosis of saporin by these cells.

PMID- 18830890
TI  - Alterations in CD4+, CD8+, Vgamma3, Vgammadelta, and/or Valpha betaT-lymphocyte
      expression in lymphoid tissues of progeny after in utero exposure to
      benzo(alpha)pyrene.
AB  - That benzo alpha)pyrene (Balpha P) decreases both humoral and cell-mediated
      immunity, and leads to increases in progeny tumor development after in utero
      insult, suggests that T- and B-lymphocytes are made defective in exposed
      offspring. In the study here, C3H mice were injected once with Balpha P (150
      microg/g BW) at day 12 of pregnancy and progeny lymphoid tissues were excised
      during gestation (day 18; GD18) or at 1 or 6 weeks post-partum. The isolated
      lymphoid cells were analyzed by flow cytometry/immunofluorescence or assessed for
      function. In Balpha P-exposed fetuses, thymic Thy1(+) cell levels were decreased
      (relative to levels in organs of corn oil-exposed dam progeny). In addition, for
      up to 6 weeks post-birth, CD4(+)CD8(+) (double positive; DP) cells were virtually
      absent and levels of CD4(-)CD8(-) (double negative; DN) cells were consistently
      at epsilon 90%. With regard to single positive (SP) cells, CD4(+) cell levels
      were also decreased in tissues at GD18 up through 6 weeks post-birth; CD8(+) cell
      levels were increased, but only in pups at 1-week and 6-weeks post-birth. In 1
      week-old progeny, spleen CD8(+) cell levels were quantitatively unchanged, though
      CD4(+) levels were reduced 2-4-fold and CD4(-)CD8(-) DN levels significantly
      increased. With respect to TCRs, fetal levels of thymic CD3Vgamma(3)(+) and
      CD3Vgamma delta(+) cells were decreased; levels of CD3Valphabeta cells were only
      slightly depressed. The latter results contrast sharply with a strong reduction
      in CD3Valphabeta cells in the fetal livers of Balpha P-exposed progeny.
      Interestingly, these livers also strongly evidenced a presence of BalphaP-7,8
      dihydrodiol-9,10-epoxide metabolite. When assessed for any change in function,
      the CD4(+), Thy1(+) cells isolated from Balpha P-exposed progeny tissues
      responded weakly (relative to controls) to ConA and in an allogeneic MLR. Taken
      in totality, the results here strengthen our original hypothesis that BalphaP can
      create a favorable milieu for tumor growth progression in progeny of exposed
      mothers by affecting development of sufficient numbers of functional lymphocytes
      in the offspring.

PMID- 18830891
TI  - The humoral immune response of mice exposed to simulated road paving-like asphalt
      fumes.
AB  - Asphalt is a complex mixture of organic molecules, including polycyclic aromatic
      hydrocarbons (PAH), which have been reported to cause serious adverse health
      effects in humans. Workers in manufacturing and construction trades exposed to
      asphalt are potentially at risk for being exposed to asphalt fumes and PAHs.
      Epidemiological investigations have collected mounting evidence that chemicals
      found in asphalt fumes present carcinogenic and possibly immunotoxic hazards.
      Studies evaluating the immunotoxic effects of asphalt fume are limited due to the
      large number of variables associated with asphalt fume exposures. This work
      investigates the immuno-toxic effects of road paving-like asphalt fume by
      analyzing the in vivo IgM response to a T-dependent antigen after exposure to
      whole, vapor, and particulate phase road paving-like asphalt fumes and asphalt
      fume condensate. Systemic exposures via intraperitoneal injection of asphalt fume
      condensate (at 0.625 mg/kg) and the particulate phase (at 5 mg/kg) resulted in
      significant reductions in the specific spleen IgM response to SRBC. Pharyngeal
      aspiration of the asphalt fume condensate (at 5 mg/kg) also resulted in
      significant suppression of the IgM response to SRBC. A significant reduction in
      the specific spleen IgM activity was observed after inhalation exposure to whole
      asphalt fumes (35 mg/m(3)) and the vapor components (11 mg/m(3)). Dermal
      exposures to the asphalt fume condensate resulted in significant reductions in
      the total (at 50 mg/kg) and specific (at 250 mg/kg) spleen IgM response to SRBC.
      These results demonstrate that exposure to road paving-like asphalt fumes is
      immunosuppressive through systemic, respiratory, and dermal routes of exposure in
      a murine model and raise concerns regarding the potential for adverse
      immunological effects.

PMID- 18830892
TI  - Biodistribution and toxicological safety of adenovirus type 5 and type 35
      vectored vaccines against human immunodeficiency virus-1 (HIV-1), Ebola, or
      Marburg are similar despite differing adenovirus serotype vector, manufacturer's
      construct, or gene inserts.
AB  - The Vaccine Research Center has developed vaccine candidates for different
      diseases/infectious agents (including HIV-1, Ebola, and Marburg viruses) built on
      an adenovirus vector platform, based on adenovirus type 5 or 35. To support
      clinical development of each vaccine candidate, pre-clinical studies were
      performed in rabbits to determine where in the body they biodistribute and how
      rapidly they clear, and to screen for potential toxicities (intrinsic and
      immunotoxicities). The vaccines biodistribute only to spleen, liver (Ad5 only),
      and/or iliac lymph node (Ad35 only) and otherwise remain in the site of injection
      muscle and overlying subcutis. Though approximately 10(11) viral particles were
      inoculated, already by Day 9, all but 10(3) to 10(5) genome copies per mu g of
      DNA had cleared from the injection site muscle. By three months, the adenovector
      was cleared with, at most, a few animals retaining a small number of copies in
      the injection site, spleen (Ad5), or iliac lymph node (Ad35). This pattern of
      limited biodistribution and extensive clearance is consistent regardless of
      differences in adenovector type (Ad5 or 35), manufacturer's construct and
      production methods, or gene-insert. Repeated dose toxicology studies identified
      treatment-related toxicities confined primarily to the sites of injection, in
      certain clinical pathology parameters, and in body temperatures (Ad5 vectors) and
      food consumption immediately post-inoculation. Systemic reactogenicity and
      reactogenicity at the sites of injection demonstrated reversibility. These data
      demonstrate the safety and suitability for investigational human use of Ad5 or
      Ad35 adenovector-based vaccine candidates at doses of up to 2 x 10(11) given
      intramuscularly to prevent various infectious diseases.

PMID- 18830893
TI  - Effect of polycyclic aromatic hydrocarbons and carbon black particles on pro
      inflammatory cytokine secretion: impact of PAH coating onto particles.
AB  - It has been suggested that the organic fraction of particulate matter in air
      pollution has a major role in the toxicity of this pollutant, notably via its
      effects on inflammation. The major organic compounds adsorbed onto these
      particles are polycyclic aromatic hydrocarbons (PAH), among which benzo[a]pyrene
      (B[a]P), benzo[b]fluoranthene (B[b]F), and pyrene (Pyr) are quantitatively the
      most important. Generally, cells or organisms are exposed to organic extracts of
      the particles rather than the native particles in order to study the effects of
      these PAH. In this study, B[a]P, B[b]F, and Pyr were tested alone and/or adsorbed
      onto carbon black (CB) particles differing in size in order to evaluate their
      impact on cytokine production (with or without LPS stimulation) by THP-1
      macrophage-like cells. PAH induced significant secretion of IL-1beta, IL-8, and
      IL-12 after 24 or 48 hr of treatment, an effect reinforced by LPS stimulation; no
      effect on IL-10 secretion was noted. Fine CB particles (260 nm diameter) induced
      secretion of each cytokine. In general, coating the CB with PAH did not modify
      the effect of the CB alone; the exception was that LPS-induced IL-1beta secretion
      was reduced. In contrast, ultrafine CB (14 nm diameter: ufCB) caused a decrease
      in cytokine secretion; this effect was modified by PAH coating. For example, PAH
      coating on ufCB amplified the inhibitory effect of ufCB against IL-1beta
      secretion but did not modify IL-8 formation. Moreover, PAH coating on ufCB tended
      to minimize the effect of LPS stimulation; this included (i) inhibition of the
      decrease in IL-12 secretion induced by uncoated ufCB and (ii) stimulation of IL
      10 production. It was concluded that adsorption of PAH onto these particles could
      decrease their bioavailability and so their abilities to affect cell cytokine
      production. The results also showed that when PAH were adsorbed onto the fine
      particles, any observed increases in cytokine secretion consistently appeared to
      be due to the particles themselves. In contrast, while ufCB alone almost
      uniformly led to decreases in cytokine formation by the cells, the added presence
      of the test PAHs led to variable effects - depending on whether stimulation with
      LPS took place or not. Thus, while some PAHs likely to be associated with PM are
      clearly immunomodulants, their ultimate effects in situ will likely depend on the
      properties of the particles themselves, in particular, their size.

PMID- 18830895
TI  - Examination of blood haemoglobin concentration measured using the OSM2.
AB  - Blood haemoglobin concentration is regularly measured automatically by
      instruments reporting the value in around 1 min. The OSM2 from Radiometer is an
      example. Results from this instrument have been compared with those of a
      reference method using the hemiglobincyanide principle. Four healthy, moderately
      trained, young men (non-smokers) cycled for 2 min to exhaustion. Blood samples
      were drawn from indwelling catheters in the femoral artery and vein before
      exercise, during exercise and in the 1 h recovery. Blood haemoglobin
      concentration was analysed using both methods. The results of the OSM2 were
      linearly related to those of the control method, with a random variation of 0.14
      mmol L(-1) (1.5%). For arterial blood, the OSM2 showed a systematic bias of -0.36
      mmol L(-1) (-4%). For femoral venous samples the bias varied depending on the
      haemoglobin concentration, being negative at low concentrations and positive at
      high values (-3 to +2%). Consequently, the arteriovenous (a-v) difference
      differed systematically between the two methods. The varying bias in the results
      of the OSM2 for femoral-venous samples correlated with pH, pCO(2), O(2)
      saturation of haemoglobin (sO(2)) and with the haemoglobin concentration itself
      (cHb). Partial correlation analyses suggest that only the latter two correlations
      were independent, while correlations of the bias with pH and pCO(2) were removed
      when correcting for the effect of sO(2) and cHb. In conclusion, the OSM2 measures
      the blood haemoglobin concentration fairly precisely, but there is a variable
      bias of up to 4% in absolute value. Finally, the instrument does not report a-v
      differences reliably.

PMID- 18830896
TI  - Elevated plasma adiponectin and decreased plasma homocysteine and asymmetric
      dimethylarginine in children with type 1 diabetes.
AB  - OBJECTIVE: Type 1 diabetes has a bad prognosis concerning the pathogenesis of
      cardiovascular diseases (CVD). The purpose of this study was to evaluate
      different possible new risk indices for CVD in children with type 1 diabetes.
      MATERIAL AND METHODS: The present study included 30 children with diabetes (mean
      HbA1C 9.8%), aged between 4.7 and 18.6 years and with no clinical evidence of
      vascular complications, and 30 healthy subjects matched by sex, age and body mass
      index. Blood pressure was measured and blood samples were obtained for lipid
      profile, creatinine, glucose, high sensitive C-reactive protein (hsCRP),
      intercellular adhesion molecule-1 (ICAM-1), asymmetric dimethylarginine (ADMA),
      adiponectin and homocysteine. RESULTS: Children with diabetes had significantly
      higher blood pressure, plasma hsCRP, ICAM-1, adiponectin levels and lower
      homocysteine, ADMA concentrations than their control subjects. In multivariate
      regression analysis, the best predictors for systolic blood pressure were
      diabetes group, plasma homocysteine concentration and BMI (Adj R(2) = 0.38,
      p<0.0001), and for diastolic blood pressure diabetes group and triglycerides
      level (Adj R(2) = 0.27, p<0.0001). CONCLUSIONS: Children with diabetes, in view
      of their higher future risk of CVD, are characterized by a higher concentration
      of protective adiponectin and paradoxically lower blood concentrations of some
      other possible risk markers of atherosclerosis, i.e. ADMA and homocysteine
      compared to healthy children.

PMID- 18830897
TI  - Effects of five different drinks on patients with Crohn's disease.

PMID- 18830898
TI  - Alterations of peripheral blood CD5+ B cells in inflammatory bowel disease.
AB  - OBJECTIVE: CD5(+) B cells comprise a unique subset of B cells that modulates
      innate as well as autoimmune systems. The aim of this study was to investigate
      alterations of the circulating CD5(+) B-cell subset in patients with inflammatory
      bowel disease (IBD) by evaluating various clinical parameters, including
      therapeutic regimens. MATERIAL AND METHODS: Thirty-four patients with ulcerative
      colitis (UC), 19 patients with Crohn's disease (CD), and 46 healthy control
      subjects were enrolled in this study. CD5(+) B cells in peripheral blood
      collected from each subject were analyzed by flow cytometry. Multiple regression
      analysis was carried out to evaluate the factors related to the circulating
      CD5(+) B-cell subset in the IBD patients. In an in vitro examination,
      dexamethasone-induced apoptosis in peripheral blood B cells was examined by
      detecting cell surface binding of the annexin-V antibody. RESULTS: Age and gender
      in the control subjects did not influence the circulating CD5(+) B-cell subset.
      Multiple regression analysis showed that the presence of UC, corticosteroid
      therapy, and number of white blood cells in peripheral blood each had a
      significant influence in decreasing the number of circulating CD5(+) B cells in
      the IBD patients. Furthermore, in vitro results showed that dexamethasone
      treatment significantly induced apoptosis in CD5(+) B cells, though apoptosis was
      similarly observed in CD5(-) B cells. CONCLUSIONS: CD5(+) B cells may be involved
      in the pathogenesis of UC, and modulation of this subset by corticosteroid
      therapy may play a role in the treatment of IBD patients.

PMID- 18830899
TI  - Curcumin reverses attenuated carbachol-induced contraction of the colon in a rat
      model of colitis.
AB  - BACKGROUND: Curcumin ameliorates colitis whether it reverses colitis-induced
      reduction in colonic contractility remains to be investigated. OBJECTIVES: To
      investigate the effect of curcumin on colitis-induced reduction of carbachol
      induced contraction in colon segments from rats treated with
      trinitrobenzenesulphonic acid. METHODS: Colitis was induced in rats by intra
      rectal administration of trinitrobenzenesulphonic acid and followed for 5 days. A
      group of animals which received trinitobenzene sulphonic acids was treated with
      curcumin (100 mg/Kg and 200 mg/kg body weight) 2 hrs prior to induction of
      colitis. The controls received phosphate buffered saline in a similar fashion.
      Markers of inflammation and contractility of colon were assayed using standard
      procedures. RESULTS: Induction of colitis was associated with increased
      myeloperoxidase activity and malondialdehyde levels, gross histological changes
      characterized by infiltration of inflammatory cells. All these changes were
      prevented by treatment with curcumin (100 mg/kg). Treatment with curcumin also
      reduced the histological scores from 3.34+/-0.40 to 1.75+/-0.30 confirming an
      anti-inflammatory effect of curcumin in this experimental model of colitis.
      Colonic reactivity to carbachol was decreased in colitis affecting the maximum
      response but not sensitivity. Treatment with curcumin had no effect on
      sensitivity of the colon to carbachol in any of the preparations. Curcumin
      however reversed the decrease in carbachol-induced contraction associated with
      trinitrobenzenesulphonic acid treatment. The same dose of curcumin had no effect
      on either the potency of or the maximum response to carbachol in control rats.
      Tissue expression of NF-kB was increased in colon segments from
      trinitrobenzenesulphonic acid -treated rats and this was inhibited in rats
      treated with curcumin. CONCLUSIONS: Based on these findings it is concluded that
      curcumin prevented the reduction in carbachol-induced contraction in
      trinitrobenzenesulphonic acid -treated rats by modulating NF-kB signaling
      pathway.

PMID- 18830900
TI  - Molecular mechanisms of cleft lip formation in CL/Fr mice.
AB  - CL/Fr mice have a high incidence of cleft lip and the cleft lip is the result of
      incomplete fusion between the medial and lateral nasal prominences and the
      maxillary prominence at about day 11.5 of gestation. However, little is known
      about the molecular mechanisms that are responsible for the incomplete fusion. We
      made a molecular pathological investigation using 11.5-day CL/Fr embryos. Five
      embryos were each examined for real-time polymerase chain reaction (PCR)
      analysis. During the first palatal formation in normal development, an epithelial
      seam is formed when the medial and lateral nasal prominences first make contact.
      Some epithelial cells of the epithelial seam then undergo apoptosis, with
      remaining cells transforming into a mesenchymal phenotype (epithelial-mesenchymal
      transition, EMT). Mesenchymal cells of the medial and lateral nasal prominences
      then merge across the previous boundary of separation. In CL/Fr mice with cleft
      lip, neither apoptosis nor EMT occurs in the epithelial cells. Increased
      expression of claudin 6 mRNA is seen in epithelial cells of epithelial seam in
      cleft lip compared with that in normal embryos. Slug mRNA expression was also
      significantly reduced whereas noggin was increased in CL/Fr embryos with cleft
      lip. We suggest that EMT is prevented in CL/Fr mice with cleft lip by increased
      expression of claudin 6 and coexistent downregulation of slug in cells of the
      epithelial seam, and these altered concentrations of transcription
      factors/repressors prevent fusion of the medial and lateral nasal prominences,
      leading to clefts of the lip.

PMID- 18830901
TI  - Arteriovenous malformation of the brain mimicking primary central nervous system
      vasculitis.
AB  - In the diagnosis of primary central nervous system (CNS) vasculitis, it is
      crucial to rule out clinical, angiographic, and pathological mimics. We report a
      case of arteriovenous malformation (AVM) mimicking primary CNS vasculitis. A
      young male presented with intracerebral haemorrhage and no other clinical,
      laboratory, or angiographic features suggesting vasculitis. Cerebral biopsy
      showed perivascular inflammation and slight infiltration of the muscular layer of
      cerebral vessels by chronic inflammatory cells close to the haemorrhagic areas.
      These findings led to a diagnosis of CNS vasculitis. The patient was initially
      treated with corticosteroids, but 10 months after the discovery and surgical
      repair of the AVM, the patient is not receiving any immunosuppressant and has not
      developed any features of cerebral or systemic vasculitis.

PMID- 18830902
TI  - Primary Sjogren's syndrome and sarcoidosis: coexistence more than by chance?

PMID- 18830903
TI  - Cocaine-induced midline destructive lesions mimicking ENT-limited Wegener's
      granulomatosis.
AB  - The prevalence of cocaine use is rising worldwide, with a resultant rise in
      associated pathology. Regular nasal use can cause cocaine-induced midline
      destructive lesions (CIMDL), which can be difficult to distinguish from ear,
      nose, and throat (ENT)-limited Wegener's granulomatosis (WG). Two cocaine users
      presented with mid-facial pain, epistaxis, and systemic symptoms. Both had nasal
      septal perforation, necrosis of sinus mucosa, and positive anti-neutrophil
      cytoplasmic antibodies (ANCA). Histology was inconclusive and treatment with
      immunosuppressive drugs was commenced. The first patient continued to use cocaine
      initially, with improvement in her symptoms only on high doses of steroid. Later
      she stopped cocaine and this plus a switch from cyclophosphamide to mycophenolate
      mofetil resulted in successful symptom resolution and steroid withdrawal. The
      second patient denied cocaine use but having only partially responded to high
      dose prednisolone and methotrexate, she admitted continued cocaine use and was
      lost to follow-up. Evaluation of a patient with destructive lesions of the mid
      face should include enquiry about intranasal use of cocaine. Localized ENT
      involvement, inconsistent ANCA pattern, and atypical biopsy findings for WG
      should be recognized as features of CIMDL. Although cessation of cocaine use is
      crucial, there may be a role for immunosuppression.

PMID- 18830904
TI  - Modulatory effects of inflammation and therapy on GDF-5 expression in rheumatoid
      arthritis synovium.
AB  - OBJECTIVE: Growth differentiation factor-5 (GDF-5), a member of the transforming
      growth factor (TGF)-beta family, is involved in joint development during
      embryogenesis and has the potential to regenerate cartilage in adult animals. As
      progression of chronic joint diseases is influenced by cytokines of the synovial
      tissue, we examined the expression and effects of GDF-5 in this tissue. METHODS:
      Microarray experiments were investigated for differential expression of GDF-5 in
      synovial tissues, synovial fibroblasts, and peripheral blood cells. GDF-5
      expression was validated by semiquantitative reverse transcriptase polymerase
      chain reaction (RT-PCR), immunohistochemistry, double immunofluorescence, and in
      situ hybridization in synovial tissue of normal donors (ND) and patients with
      osteoarthritis (OA) and rheumatoid arthritis (RA). Effects of inflammation and
      therapy were investigated in RA and OA fibroblasts after stimulation with
      interleukin (IL)-1beta, tumour necrosis factor (TNF)-alpha, methotrexate (MTX),
      and prednisolone. The influence of GDF-5 on macrophages was studied by chemotaxis
      assay. RESULTS: Microarray analysis and immunostaining revealed expression
      predominantly in synovial fibroblasts. Compared to patients without
      immunomodulating drugs, expression of GDF-5 was decreased significantly in
      patients receiving glucocorticoids and/or disease-modifying antirheumatic drugs
      (DMARDs) (p = 0.007), but did not differ between the total group of ND, OA, and
      RA. Stimulation with prednisolone and TNFalpha reduced GDF-5 expression in OA and
      RA fibroblasts, whereas MTX and IL-1beta revealed minor or no relevant change.
      GDF-5 also reduced cell migration of macrophages (p<0.001). CONCLUSION: GDF-5 is
      expressed in synovial fibroblasts and may counteract macrophage infiltration. Its
      modulation by inflammation and therapy suggests that glucocorticoids play a
      conflicting role by suppressing not only inflammation but also putative
      mechanisms of repair.

PMID- 18830905
TI  - Changes in disease activity, cytokine production, and proliferation of peripheral
      blood mononuclear cells in patients with rheumatoid arthritis after simvastatin
      treatment.
AB  - OBJECTIVES: The aim of this study was to investigate changes in disease activity,
      cytokine profiles, and proliferation of peripheral blood mononuclear cells
      (PBMCs) in active rheumatoid arthritis (RA) patients treated with simvastatin.
      METHODS: Thirty-three patients with active RA were prescribed simvastatin (40
      mg/day) for 3 months. Most of the patients received background traditional
      disease-modifying anti-rheumatic drugs (DMARDs) in stable doses. At the end of
      treatment there was a reduction in the 28-joint Disease Activity Score (DAS28)
      and in the Health Assessment Questionnaire (HAQ) score. RESULTS: Eleven patients
      (33%) achieved a moderate European League Against Rheumatism (EULAR) response.
      There was a decrease in circulating interleukin (IL)-17 concentrations and
      spontaneous PBMC proliferation. Anti-CD3-stimulated IL-10 and tumour necrosis
      factor (TNF)alpha production by PBMCs was upregulated after simvastatin therapy.
      A reduction in serum IL-6 was detected only in the responder group. Baseline
      circulating IL-10 concentrations were higher in responders than in non
      responders. CONCLUSION: Simvastatin treatment is associated with moderate
      clinical improvement in patients with active RA. Immunological changes produced
      by simvastatin in peripheral blood are complex and may reflect both its anti- and
      pro-inflammatory properties.

PMID- 18830906
TI  - Glucocorticoid receptor variants may predispose to rheumatoid arthritis
      susceptibility.
AB  - OBJECTIVES: Deregulation of glucocorticoid (GC) secretion could be associated
      with rheumatoid arthritis (RA). The GC receptor (GR) has two isoforms. In the
      present study, we explored the role of GR-alpha polymorphisms rs33388, rs33389,
      and Bcl I, and the GR-beta variant rs6198 in RA susceptibility. METHODS: One
      hundred and thirty-six RA patients and 148 ethnic matching controls were studied.
      Polymorphisms rs33388 and Bcl I were genotyped by polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP), and variants rs33389 and
      rs6198 by polymerase chain reaction single-strand conformation polymorphism (PCR
      SSCP) coupled with sequencing. Arlequin and SPSS softwares were used in the
      statistical analysis. RESULTS: The polymorphisms studied were in Hardy-Weinberg
      equilibrium in both groups. A marginally statistical significant difference was
      observed in the distribution of rs33388 genotypes between RA patients and
      controls (p = 0.053). When the A and T alleles were compared, the statistical
      significance was p = 0.025. Specific complex genotypes were also differentially
      distributed: the GR-alpha complex genotypes (a) [homozygote (homo) wild-type (wt)
      rs33388-homo wt rs33389] (11% RA vs. 21% controls; p = 0.023), (b) [homo wt
      rs33388-homo wt rs33389-homo non-wt Bcl I] (0.7% RA vs. 4.7% controls; p =
      0.042), and (c) the GR-beta complex genotype [homo wt rs33388-homo wt rs33389
      homo non-wt Bcl I-homo wt rs6198] (0.7% RA vs. 4.7% controls; p = 0.042).
      CONCLUSIONS: GR-alpha and GR-beta polymorphisms are potentially associated with
      RA susceptibility. However, additional studies in larger and other ethnic groups
      of patients are needed to confirm the results of the present study.

PMID- 18830907
TI  - Brain-derived neurotrophic factor and nerve growth factor correlate with T-cell
      activation in primary Sjogren's syndrome.
AB  - OBJECTIVES: Identification of factors associated with disease activity and B and
      T cell activation is a challenge in primary Sjogren's syndrome (pSS).
      Neurotrophins (NTs), recently reported as B cell antiapoptotic, and T-cell
      activation factors seem to be implicated in autoimmune diseases such as systemic
      lupus erythematosus (SLE) and rheumatoid arthritis (RA). METHODS: Samples from 18
      pSS patients and 12 control subjects were studied to determine serum levels of
      nerve-growth factor (NGF) and brain-derived neurotrophic factor (BDNF), and their
      relationships with T- and B-cell activation and disease activity. Peripheral
      blood mononuclear cells (PBMCs) from patients with pSS and controls were examined
      by flow cytometry for HLA-DR expression by activated T cells. B cell activation
      was evaluated by B cell activating factor (BAFF) serum levels measured by enzyme
      linked immunosorbent assay (ELISA) and immunoglobulin (Ig) and free light chain
      (FLC) levels. RESULTS: Mean serum levels of BDNF in pSS patients were
      significantly higher than in healthy controls and correlated directly with
      disease activity. NGF levels were associated with the subgroup of patients with
      hypergammaglobulinaemia. The pSS group was characterized by peripheral CD4+ and
      CD8+ T cell activation that correlated positively with BDNF and NGF levels,
      respectively. CONCLUSION: NT levels are potential biomarkers for lymphocyte
      activation in pSS patients.

PMID- 18830910
TI  - AAC interventions for children in a family environment: implementing evidence in
      practice.
AB  - Interventions that focus on implementing augmentative and alternative
      communication (AAC) strategies and methods have been available to children in
      need of AAC and their families for at least 30 years. To date, most of the
      research that has considered AAC in family settings has been focused on gathering
      evidence of the effects of AAC interventions, rather than on implementing
      evidence-based strategies in everyday practice to improve outcomes. The purpose
      of this article is to discuss the research that has focused on parents as AAC
      interventionists, the family as a context for AAC intervention, and the effects
      of AAC interventions on children and other family members. The discussion is
      framed within the four steps associated with the process of knowledge
      translation: (a) deciding on desired outcomes of interventions, (b) evaluating
      evidence of the effectiveness of different AAC methods to obtain the desired
      outcomes, (c) translating the research evidence into everyday practice, and (d)
      implementing knowledge in practice.

PMID- 18830911
TI  - A back door approach to autism and AAC.
AB  - The conventional view is that most individuals with autism or pervasive
      developmental disorder-not otherwise specified (PDD-NOS) have no significant
      motor impairments but do have severe intellectual disabilities. These assumptions
      impact the nature and types of augmentative and alternative communication (AAC)
      interventions that are typically provided, which tend to be narrowly focused on
      basic, functional communication skills such as requesting. However, recent
      research has provided evidence that challenges these assumptions and suggests the
      potential of intervention approaches targeting motor, language, and literacy
      development. The author encourages practitioners and researchers to examine
      current assumptions about autism and to invent and investigate new ways to
      support people with autism to communicate.

PMID- 18830912
TI  - Whole utterance approaches in AAC.
AB  - Increased communication rate has long been a goal of both individuals who use AAC
      and device manufacturers. There is evidence that utterance-based approaches have
      the potential to deliver faster rates without loss of coherence. An overview of
      the historical development of devices that embody such approaches is set out
      here. This account focuses on the theoretical origins of utterance-based devices
      (UBDs) and the range of approaches that these have produced. Next, the issue of a
      causal relationship between conversational rate and positive attributions is
      addressed. Three recent studies supporting a causal relationship are described,
      followed by an account of a direct comparison between a UBD and a word
      construction system in office environments that involved a mix of transactional
      communication and social chat. Conversational rate and perceived communicative
      competence were both higher when the UBD was used. Finally, some issues for the
      future development of UBDs are discussed.

PMID- 18830913
TI  - An AAC personnel framework: adults with acquired complex communication needs.
AB  - A personnel framework designed to support people who rely on augmentative and
      alternative communication (AAC) because of acquired medical conditions and those
      who assist them is described. The roles of AAC finders, general practice
      clinicians, AAC intervention specialists, AAC facilitators, and AAC experts are
      summarized. These roles are described in detail for people with amyotrophic
      lateral sclerosis, brainstem impairment, and severe chronic aphasia. The
      personnel preparation needs for each of these support personnel groups are
      identified.

PMID- 18830914
TI  - Synthesis, characterization and antimicrobial activities of some mixed ligand
      complexes of Co(II) with thiosemicarbazones and N-protected amino acids.
AB  - The reaction of cobalt(II) chloride with a new class of thiosemicarbazones viz;
      cis-3,7-dimethyl-2,6-octadienthiosemicarbazone(CDOTSC; L(1)H) and 3,7-dimethyl-6
      octenethiosemicarbazone (DOTSC; L(2)H) and N-phthaloyl derivative of DL
      glycine(A(1)H), L-alanine(A(2)H) or L-valine(A(3)H) in 1:1:1 molar ratio in dry
      refluxing ethanol have been studied. All the isolated complexes have the general
      composition [Co(L)(A)]. Tentative structures are proposed for these complexes
      based upon elemental analysis, electrical conductances, magnetic moment,
      molecular weight determination and spectral (IR, electronic) studies.The ligands
      and Co(II) complexes have been tested for their antibacterial and antifungal
      activities against three bacterial strains S. aureus, B. subtilis, E. coli and
      two fungal strains F. moniliformae and M. phaseolina. Attempts have been made to
      establish a correlation between the antibacterial and antifungal activity and the
      structures of products.

PMID- 18830915
TI  - Thyroglobulin may affect telomerase activity in thyroid follicular cells.
AB  - Telomerase (TA) activity is known to be present in malignant tumor cells, but not
      in most somatic differentiated cells. TA shows relatively high activity in
      thyroid cancer cells, but reports vary. This fact prompted us to elucidate
      whether cell component inhibitors of TA in the thyroid follicles can modulate its
      activity. The activity of TA extracted from Hela cells was inhibited by mixing
      with the supernatant fraction of human thyroid tissue extract. To examine the
      effect of iodine, thyroid hormones (l-T3 and l-T4) and human thyroglobulin (hTg)
      contained in the thyroid follicles, l-T3, l-T4 and hTg were added to the TRAP
      assay system in vitro, using TA from Hela cells. Iodine, l-T3 and l-T4 did not
      affect TA activity, but hTg inhibited the TA activity in a dose-dependent manner
      (IC(50) of hTg: ca 0.45 microM: inhibiting concentration of hTg was from 0.15
      microM to 3.0 microM). The hTg inhibition was not evident in the RT-PCR system,
      suggesting no effect of hTg on Taq DNA polymerase activity. The hTg inhibition of
      TA activity was attenuated by dNTP but not significantly by TS primer. These data
      suggest that hTg contained in thyroid follicular cells of various thyroid
      diseases may affect the TA activity measured in biopsied thyroid specimens, and
      that the reduction of the TA activity by hTg may induce slow progression and
      growth, and low grade malignancy of thyroid cancer, particularly differentiated
      carcinoma.

PMID- 18830916
TI  - Differential in vitro inhibition of polyphenoloxidase from a wild edible mushroom
      Lactarius salmonicolor.
AB  - The polyphenol oxidase (LsPPO) from a wild edible mushroom Lactarius salmonicolor
      was purified using a Sepharose 4B-L-tyrosine-p-amino benzoic acid affinity
      column. At the optimum pH and temperature, the K(M) and V(Max) values of LsPPO
      towards catechol, 4-methylcatechol and pyrogallol were determined as 0.025 M &
      0.748 EU/mL, 1.809 x 10(- 3) M & 0.723 EU/mL and 9.465 x 10(- 3) M & 0.722 EU/mL,
      respectively. Optimum pH and temperature values of LsPPO for the three substrates
      above ranged between the pH 4.5-11.0 and 5-50 degrees C. Enzyme activity
      decreased due to heat denaturation with increasing temperature. Effects of a
      variety of classical PPO inhibitors were investigated opon the activity of LsPPO
      using catechol as the substrate. IC(50) values for glutathione, p
      aminobenzenesulfonamide, L-cysteine, L-tyrosine, oxalic acid, beta
      mercaptoethanol and syringic acid were determined as 9.1 x 10(- 4), 2.3 x 10(- 4)
      M, 1.5 x 10(- 4) M, 3.8 x 10(- 7) M, 1.2 x 10(- 4) M, 4.9 x 10(- 4) M, and 4 x
      10(- 4) M respectively. Thus L-tyrosine was by far the most effective inhibitor.
      Interestingly, sulfosalicylic acid behaved as an activator of LsPPO in this
      study.

PMID- 18830917
TI  - Clinical trials in gene therapy: ethics of informed consent and the future of
      experimental medicine.

PMID- 18830918
TI  - Retrovirus-induced oncogenesis and safety of retroviral vectors.
AB  - Gene therapy using genome-integrating vectors carrying corrective genes offers
      great potential for the treatment of diseases with an association to genetic
      defects. Retroviral vectors are still by far the most efficient tools for gene
      therapy. However, the induction of T-cell lymphoproliferative disease in four
      patients with X-linked SCID undergoing retroviral gene therapy demonstrated the
      requirement for an improved knowledge of the genetic and molecular effects of
      retroviruses on the host. This review investigates developments on the molecular
      mechanisms of oncogenesis by retroviruses and examines how safer vectors could be
      designed. The target sites of integration, the most crucial factor associated
      with oncogenicity, are distinct for different retroviruses and should be
      considered when choosing vectors. Furthermore, insertional activation of non
      coding sequences, such as microRNAs, in addition to insertional effects on
      protein-coding genes, should be examined when considering the risks of retroviral
      therapy.

PMID- 18830919
TI  - Interactions of adenovirus vectors with blood: implications for intravascular
      gene therapy applications.
AB  - Despite various obstacles the promise of gene therapy has begun to be realized,
      as demonstrated by the successful phenotypic correction of X-linked SCID in
      infants. Although ex vivo gene therapy is advantageous, many diseases, for
      example, disseminated cancers, require intravascular administration of the gene
      therapy vector in vivo. In this scenario, the development of sophisticated
      vectors suitable for targeted intravascular gene delivery is required to both
      improve efficacy and minimize toxicity. Vectors based on adenovirus (Ad) show
      immense promise because they are highly efficient in transducing non-dividing
      cells, can tolerate substantial genetic manipulation (eg, the incorporation of
      targeting agents), can be produced to high titer, do not integrate into the
      genome, and have undergone significant investigation in the clinic. However, the
      use of Ad-based vectors is limited by the inherent hepatic tropism of
      intravascularly administered Ad, which precludes targeted delivery to alternative
      organs or disease sites, and by the associated host inflammatory responses to the
      vector. An improved knowledge of the complex series of interactions is of
      fundamental importance to the field. This review discusses the current
      understanding of Ad vector and host interactions, as well as suitable
      technologies for optimizing delivery to target cells in vivo.

PMID- 18830920
TI  - HSV vectors for gene therapy of chronic pain.
AB  - Chronic pain is a serious debilitating condition affecting a large number of
      individuals and with substantial societal impact in terms of quality-of-life and
      absence from work. Current therapies often exhibit activity at sites other than
      the nervous system and so are limited by 'off-target' adverse effects. These
      adverse effects often prevent the administration of an effective therapeutic dose
      of the approved drug(s). Viral vectors have the potential to deliver and express
      short-lived, but potent therapeutic peptides in the nervous system. Vector
      expressed peptides interrupt or modulate the transmission of nociceptive signals
      without systemic distribution or off-target effects. This review focuses on the
      use of non-replicating HSV-based vectors that are introduced into the skin and
      transduce dorsal root ganglia to express analgesic molecules locally in the
      spinal cord. Data from preclinical animal models as well as studies that support
      early phase clinical trials from 2002 to 2008 are described.

PMID- 18830922
TI  - Factoring nonviral gene therapy into a cure for hemophilia A.
AB  - Gene therapy for hemophilia A has fallen short of success despite several
      clinical trials conducted over the past decade. Challenges to its success include
      vector immunogenicity, insufficient transgene expression levels of Factor VIII,
      and inhibitor antibody formation. Gene therapy has been dominated by the use of
      viral vectors, as well as the immunogenic and oncogenic concerns that accompany
      these strategies. Because of the complexity of viral vectors, the development of
      nonviral DNA delivery methods may provide an efficient and safe alternative for
      the treatment of hemophilia A. New types of nonviral strategies, such as DNA
      integrating vectors, and the success of several nonviral animal studies, suggest
      that nonviral gene therapy has curative potential and justifies its clinical
      development.

PMID- 18830921
TI  - Nonviral ocular gene therapy: assessment and future directions.
AB  - For multiple reasons, the eye is an excellent organ for gene therapy and while
      nonviral gene therapy modalities have been known for quite some time, they have
      only been applied to the eye in the past decade. Despite significant advances in
      the therapeutic effectiveness of nonviral ocular gene therapy in this time
      period, the clinical utility of many strategies remains questionable. Therefore,
      in addition to a brief summary of the status of ocular gene therapy, this review
      focuses on exciting current developments in non-ocular nonviral gene therapy and
      their application to the eye. Of specific interest are three approaches that may
      help to overcome the common limitations of transience in transgene expression and
      include the use of: (i) integrating vector systems, such as the Sleeping Beauty
      transposon-transposase system and the phiC31 integrase system; (ii) minicircle
      DNA to minimize prokaryotic vector-based silencing; and (iii) episomal
      replicating vectors containing chromosomal elements.

PMID- 18830923
TI  - Hematopoietic stem cell gene therapy in Hurler syndrome, globoid cell
      leukodystrophy, metachromatic leukodystrophy and X-adrenoleukodystrophy.
AB  - Hurler syndrome, metachromatic leukodystrophy, globoid-cell leukodystrophy
      (Krabbe's disease) and X-linked adrenoleukodystrophy are inherited diseases of
      the CNS that can be cured or arrested by allogeneic hematopoietic stem-cell
      transplantation (HSCT). Despite significant progress in medical procedures and
      the availability of banked umbilical cord blood, HSCT is still associated with
      significant risks of graft failure or GVHD that can lead to death.
      Transplantation of autologous hematopoietic stem cells genetically modified to
      express the missing protein may circumvent the majority of the problems
      associated with allogeneic HSCT. Promising in concept, these strategies are now
      at a stage to be tested in phase I/II clinical trials to assess safety and
      potential efficacy.

PMID- 18830924
TI  - Gene therapy of cardiovascular disease.
AB  - Coronary and peripheral artery diseases are highly prevalent and characterized by
      an unmet requirement for medical treatment in the more advanced stages. These
      shortcomings comprise the requirement for vessel regeneration using therapeutic
      angiogenesis as well as the prevention of post-angioplasty restenosis using local
      gene therapy. Both therapeutic angiogenesis and gene therapy to prevent post
      angioplasty restenosis have undergone extensive research in the past 17 years and
      have led to a number of phase II clinical trials and a phase III approval trial.
      The development of therapeutic strategies based on gene therapy over the last 7
      years is reviewed, including data from animal studies as well as phase II
      clinical trials.

PMID- 18830925
TI  - siRNA delivery by magnetofection.
AB  - Magnetofection is defined as the magnetically enhanced delivery of nucleic acids
      associated with magnetic nanoparticles and has been utilized to deliver synthetic
      siRNAs to cultured cells. Certain magnetic nanomaterials associate with siRNAs
      and are suitable for siRNA delivery, either alone or in combination with cationic
      polymers or cationic lipid enhancers; these complexes are targeted to the cell
      surface by application of a gradient magnetic field. In this review methods are
      described to examine siRNA incorporation into magnetic complexes, to evaluate
      their magnetic responsiveness and to characterize their association with, and
      uptake into cells. These methods can be utilized to screen magnetic siRNA
      complexes for their suitability in functional siRNA delivery. Data, obtained
      since the first description of magnetofection in 2000, and novel results on the
      characterization of magnetic complexes containing synthetic siRNA are described.
      In addition, the benefits of siRNA delivery in vitro via magnetofection compared
      with standard non-magnetic methods of transfection using lipoplexes and
      polyplexes are highlighted.

PMID- 18830926
TI  - NT-501: an ophthalmic implant of polymer-encapsulated ciliary neurotrophic factor
      producing cells.
AB  - Neurotech Pharmaceuticals Inc is developing NT-501, an implantable polymeric
      device containing a genetically modified cell line that secretes ciliary
      neurotrophic factor, for the potential treatment of retinitis pigmentosa (RP) and
      age-related macular degeneration (AMD). Phase III clinical trials for RP and a
      phase II clinical trial for dry AMD are ongoing. A phase I clinical trial showed
      that NT-501 treatment was well tolerated with variable, but positive improvements
      in visual acuity.

PMID- 18830927
TI  - Diamyd, an alum-formulated recombinant human GAD65 for the prevention of
      autoimmune diabetes.
AB  - Diamyd Medical AB is developing Diamyd (GAD-65), an alum formulation of a full
      length recombinant human glutamic acid decarboxylase 65 for subcutaneous
      injection, for the potential prevention and treatment of type 1 diabetes (T1DM)
      or latent autoimmune diabetes (LADA) in adults. Phase II clinical trials
      indicated that Diamyd was safe and well tolerated in patients with T1DM or LADA.
      Diamyd is currently in phase II/III and III clinical trials for T1DM.

PMID- 18830928
TI  - BiovaxID, a personalized therapeutic vaccine against B-cell lymphomas.
AB  - Biovest International Inc (a subsidiary of Accentia BioPharmaceuticals Inc),
      under license from Stanford University, is developing BiovaxID, a personalized
      therapeutic vaccine against B-cell lymphomas that, in combination with GM-CSF,
      exclusively targets cancerous B-cells by raising an immune response to tumor
      specific immunoglobulin proteins called idiotypes, for the potential treatment of
      follicular non-Hodgkin's lymphoma (NHL). Phase I and II clinical trials
      demonstrated the immunogenicity, safety and therapeutic efficacy of BiovaxID.
      Phase III clinical trials in NHL were ongoing at the time of publication.

PMID- 18830929
TI  - Reduced expression of sarcospan in muscles of Fukuyama congenital muscular
      dystrophy.
AB  - Expression profiles of sarcospan in muscles with muscular dystrophies are
      scarcely reported. To examine this, we studied five Fukuyama congenital muscular
      dystrophy (FCMD) muscles, five Duchenne muscular dystrophy (DMD) muscles, five
      disease control and five normal control muscles. Immunoblot showed reactions of
      sarcospan markedly decreased in FCMD and DMD muscle extracts.
      Immunohistochemistry of FCMD muscles showed that most large diameter myofibers
      expressed sarcospan discontinuously at their surface membranes. Immature small
      diameter FCMD myofibers usually did not express sarcospan. Immunoreactivity of
      sarcospan in DMD muscles was similarly reduced. With regard to dystroglycans and
      sarcoglycans, immunohistochemistry of FCMD muscles showed selective deficiency of
      glycosylated alpha-dystroglycan, together with reduced expression of beta
      dystroglycan and alpha-, beta-, gamma-, delta-sarcoglycans. Although the
      expression of glycosylated alpha-dystroglycan was lost, scattered FCMD myofibers
      showed positive immunoreaction with an antibody against the core protein of alpha
      dystroglycan. The group mean ratios of sarcospan mRNA copy number versus GAPDH
      mRNA copy number by real-time RT-PCR showed that the ratios between FCMD and
      normal control groups were not significantly different (P>0.1 by the two-tailed t
      test). This study implied either O-linked glycosylation defects of alpha
      dystroglycan in the Golgi apparatus of FCMD muscles may lead to decreased
      expression of sarcoglycan and sarcospan molecules, or selective deficiency of
      glycosylated alpha-dystroglycan due to impaired glycosylation in FCMD muscles may
      affect the molecular integrity of the basal lamina of myofibers. This, in turn,
      leads to decreased expression of sarcoglycans, and finally of sarcospan at the
      FCMD myofiber surfaces.

PMID- 18830930
TI  - Extensive alteration in the expression profiles of TGFB pathway signaling
      components and TP53 is observed along the gastric dysplasia-carcinoma sequence.
AB  - AIMS: The expression patterns of TGFB signaling proteins, such as TGFB1/2,
      TGFBR1(ALK5), TGFBR2, SMAD1/2/3, SMAD2/3, SMAD4, SMAD7, and of downstream targets
      of TGFB signaling, CDKN1A (p21CIP1), CDKN1B (p27KIP1), MYC, CDC25A, TP53, and
      RELA (p65NF-kB) were investigated in gastric carcinomas and other gastric
      lesions. METHODS AND RESULTS: A total of 112 gastric carcinomas, 37 dysplasias,
      54 intestinal metaplasias, 29 chronic atrophic gastritis and 54 normal gastric
      epithelium were analyzed by tissue microarray-based immunohistochemical analysis.
      Extensive changes in expression profiles of these proteins were observed. Three
      types of expression patterns were observed along the normal epithelium-atrophic
      gastritis-dysplasia-carcinoma sequence. (1) Expression of TGFB1/2, TGFBR1, MYC,
      and TP53 continually increased along this sequence. (2) Expression of SMAD4,
      CDKN1A, SMAD1/2/3, SMAD2/3, and CDKN1B was enhanced in dysplasia but decreased in
      carcinoma. (3) Expression of TGFBR2, SMAD7, RELA, and CDC25A was enhanced in
      dysplasia and the enhanced level was maintained in carcinoma. In addition, we
      also evaluated the clinical significance of the expression of TGFB signaling
      proteins in gastric carcinoma. TGFB and MYC were positively correlated with
      advanced stages, whereas SMAD1/2/3 and SMAD4 were strongly associated with
      earlier stages. CONCLUSIONS: The extensive change in expression of TGFB signaling
      components is implicated during tumorigenesis of gastric neoplasias.

PMID- 18830931
TI  - Morphological effects of oestradiol-17beta, and selective oestrogen receptor
      alpha and beta agonists on luteinising hormone-secreting cells in tamoxifen
      treated ovariectomised rats.
AB  - To investigate the role played by the different rat gonadotroph oestrogen
      receptor (ER) pools in the effects of oestradiol-17beta (E2) on gonadectomy
      cells, two-week ovariectomised (OVX) rats were used. The basic experimental group
      of rats was injected with 3 mg of the selective ER modulator tamoxifen (TX) on
      days 15-20 after OVX. Groups of TX-treated OVX rats were additionally injected on
      days 18-20 after OVX with 10 microg oestradiol benzoate (EB), 1 mg of the
      selective ERalpha agonist propylpyrazole triol (PPT), or 1 mg of the selective
      ERbeta diarylpropionitrile (DPN). Negative and positive control groups were OVX
      rats injected over six days after OVX with 0.2 ml oil and EB, respectively. On
      day 21 after OVX, anterior pituitary glands were dissected out and divided into
      halves. One hemipituitary was processed for light microscopy and
      immunocytochemistry for betaLH subunit and progesterone receptor (PR), and the
      other hemipituitary for ultrastructural evaluation. Results showed that:
      gonadotrophs were the only pituitary cell type expressing PR; treatment with TX
      alone shrunk gonadectomy cells and induced both reorganization of membrane
      enclosed intracellular organelles and PR expression, and treatment with DPN or
      EB, but not PPT, reduced the agonistic morphological effects of TX. Considering
      that TX activates nuclear ERalpha, the results indicate that activation of
      nuclear ERalpha is determinant for the reversal effects of E2 on gonadotrope
      morphology and PR expression, and the simultaneous activation of ERbeta modulates
      the action of ERalpha in an inhibitory fashion.

PMID- 18830932
TI  - Leptin and peroxisome proliferator-activated receptors: impact on normal and
      disturbed first trimester human pregnancy.
AB  - Recent in vitro and in vivo studies emphasize the impact of leptin, peroxisome
      proliferator-activated receptors (PPAR) and PPAR coactivators (retinoic X
      receptor a (RXR), amplified in breast cancer-3 gene (AIB3)) on placental and
      fetal development. Therefore, the frequency and distribution pattern of PPAR,
      RXR, AIB3 and leptin expression in normal human first trimester pregnancy,
      miscarriage and hydatidiform mole was investigated by immunohistochemistry and
      double immunofluorescence staining. Enhanced expression of PPAbeta/delta, RXR and
      AIB3 was identified in miscarried placentas. With regard to hydatidiform mole,
      increased expression of PPARgamma and PPARbeta/delta was observed, whereas RXR
      was significantly down-regulated. Leptin expression was lowest in miscarriage and
      highest in mole pregnancies. In contrast to trophoblast tissue, expression of
      leptin in glandular epithelial cells of the decidua was increased in miscarriage.
      PPAR and leptin expressing cells at the feto-maternal interface were identified
      as extravillous trophoblast (EVT) by double immunofluorescence and CK7 staining.
      In summary, significantly reduced leptin expression was accompanied by enhanced
      PPARbeta/delta, RXR and AIB3 expression in miscarried placentas. However, in mole
      pregnancy, up-regulation of leptin and increased expression of PPAR was detected.
      RXR, on the other hand, was down-regulated in mole decidua. So far, the study
      results implicate strong regulatory interaction of PPARs, their coactivators and
      leptin in human placentas. PPAR and leptin are potential targets for new
      treatment strategies concerning pregnancy disorders, such as miscarriage. The
      increasing knowledge about the role of PPARs and leptin in normal and disturbed
      pregnancy may help to improve pregnancy outcome.

PMID- 18830933
TI  - Decreased expression of antioxidant enzymes in the conjunctival epithelium of dry
      eye (Sjogren's syndrome) and its possible contribution to the development of
      ocular surface oxidative injuries.
AB  - Previous studies have described elevated lipid peroxidase, myeloperoxidase and
      xanthine oxidoreductase/xanthine oxidase levels on the ocular surface of patients
      suffering from autoimmune dry eye (Sjogren's syndrome, SS). Reactive oxygen
      species generated by various enzymatic systems may be dangerous to the eye if
      they are not sufficiently cleaved by antioxidants. Because antioxidants have not
      been investigated in dry eye, the aim of this study was to examine the expression
      of antioxidant enzymes that cleave reactive oxygen species and play a key role in
      antioxidant protection. Conjunctival epithelial cells of dry eye (SS) patients
      were obtained by the method of impression cytology using Millicell membranes.
      Normal eyes served as controls. In the conjunctival epithelium superoxide
      dismutase, catalase and glutathione peroxidase were examined
      immunohistochemically. The enzyme expression levels were determined by image
      analysis and statistical evaluation. In contrast to normal eyes, where
      antioxidant enzymes were highly expressed in the conjunctival epithelium, in dry
      eye their expression was much less pronounced in correlation with the increasing
      severity of dry eye symptoms. Our study suggests that the decreased expression of
      antioxidant enzymes in dry eye disease (SS) contributes to the development of
      anterior eye surface oxidative injuries.

PMID- 18830934
TI  - Expression of ADAMTS-5 in deformed human temporomandibular joint discs.
AB  - OBJECTIVE: To study the expression of a disintegrin and metalloproteinase with
      thrombospondin motifs 5 (ADAMTS-5) in tissue samples of deformed human
      temporomandibular joint (TMJ) discs and cells obtained from the discs. MATERIALS
      AND METHODS: Eleven adult human TMJ discs (nine diseased discs and two normal
      discs) were used in this study. The nine diseased discs were obtained from nine
      patients with internal derangement (ID) and osteoarthritis (OA) in the TMJ. These
      patients all had anteriorly displaced discs and deformed mandibular condyles,
      making conservative therapy impossible. The tissues were immunohistochemically
      stained using ADAMTS-5 antibodies. In addition, an articular disc cell line from
      one case was established by collagenase treatment. The subcultured cells under
      both normal and hypoxic conditions (O2: 2%) were incubated for 3, 6, 12 and 24 h
      after addition of interleukin-1beta (IL-1beta) (1 ng/mL). Subsequently, the
      expression of ADAMTS-5 was examined using reverse transcription-polymerase chain
      reaction (RT-PCR). RESULTS: The control group showed negative reactions on
      immunohistochemical staining. The discs extracted from cases with ID and OA
      presented positive reactions for ADAMTS-5. The expression of ADAMTS-5 mRNA
      increased under both normoxia and hypoxia with the addition of IL-1beta, and the
      peak was observed after 3 h. CONCLUSION: These results suggest that ADAMTS-5 is
      related to deformation and destruction of human TMJ discs affected by ID and OA.

PMID- 18830935
TI  - RAD50/MRE11/NBS1 proteins in relation to tumour development and prognosis in
      patients with microsatellite stable colorectal cancer.
AB  - RAD50/MRE11/NBS1 complex is essential for DNA double-strand break repair and for
      maintaining genomic integrity. In this study, we immunohistochemically examined
      MRE11, NBS1 and RAD50 expression in primary CRCs (n=208), the corresponding
      distant (n=41) and adjacent normal mucosa (n=130), and lymph node metastases
      (n=26), and investigated their clinicopathological significance in colorectal
      cancers (CRCs). We found that the intensity and percentage of MRE11 and NBS1 in
      primary CRCs were positively correlated with each other and with RAD50
      (P<0.0001). Strong expression of MRE11, NBS1 or combined RAD50/MRE11/NBS1 was
      related to MSS, positive hMLH1 expression, earlier tumour stage (TNM stage I and
      II) and favourable survival (P<0.05). A high percentage of MRE11 expression was
      associated with less local recurrence and high apoptotic activity (P<0.05). In
      MSS CRCs, the expression of MRE11 and NBS1 was stronger than that in normal
      mucosa (P<0.05), and strong expression of NBS1 in primary tumour was related to
      favourable survival of patients in TNM stage I and II (univariate analysis:
      P=0.03; multivariate analysis: P=0.07). In MSI CRCs, neither MRE11 nor NBS1
      expression showed differences among normal mucosa, primary tumour and metastasis,
      or among clinicopathological variables. In conclusion, RAD50/MRE11/NBS1 proteins
      interacted with each other, which had different clinicopathological significance
      in MSS and MSI CRCs, and further, each component of the complex might have
      additional roles. NBS1 might be a prognostic factor for patients with MSS tumour
      in TNM stage I and II.

PMID- 18830936
TI  - Temporal and quantitative analysis of expression of metalloproteinases (MMPs) and
      their endogenous inhibitors in atherosclerotic lesions.
AB  - Matrix metalloproteinases (MMPs) play an important role in the pathogenesis of
      vascular diseases, such as atherosclerosis, plaque rupture and aneurysms.
      Although several MMPs have been demonstrated in the lesions of atherosclerosis,
      their expression profiles during the initiation and progression of lesions have
      not been fully determined. We hypothesized that the expression of various MMPs,
      along with their endogenous inhibitors, may be differentially regulated dependent
      upon the lesion progression. Therefore, we made a temporal and quantitative
      analysis of the mRNA and protein expression of MMPs and tissue inhibitors of
      metalloproteinases expressed in the different stages of atherosclerotic lesions
      of rabbits and humans. We found that MMP-1, MMP-12 and MMP-13 expression was
      nearly absent in the normal arterial wall, but was remarkably increased with
      lesion progression. Furthermore, the expression of these MMPs in the lesions was
      closely associated with intimal macrophages and monocyte chemoattractant protein
      1 expression, suggesting that the intimal macrophages are the major source of
      production of these MMPs. MMP-3 and MT1-MMP were also significantly upregulated
      in the early-stage lesions and fatty streaks compared to the normal aortas of
      rabbits. Our results indicate that MMP-1, -12, and -13 derived from intimal
      macrophages may play a pivotal role in both lesion initiation and progression,
      and therefore are potential therapeutic targets for the treatment of plaque
      rupture and aneurysm formation.

PMID- 18830937
TI  - Mucinous tubular and spindle cell carcinoma with Fuhrman nuclear grade 3: a
      histological, immunohistochemical, ultrastructural and FISH study.
AB  - Mucinous tubular and spindle cell carcinoma (MTSCC) of the kidney generally shows
      low nuclear grade. MTSCC with high nuclear grade is relatively rare. In this
      article, we report two cases of MTSCC with Fuhrman grade 3. One case occurred in
      a 57-year-old Japanese female and the second case in a 49-year-old Caucasian
      female. Histologically, the tumors were composed of neoplastic cells with
      cuboidal or columnar and spindle morphology, and Fuhrman nuclear grade 3. The
      myxoid stroma was also observed. This stroma was positive for Alcian blue stain.
      Immunohistochemically, neoplastic cells of both cases were positive for AMACR,
      but negative for CD10 and RCC Ma. Ultrastructurally, tumorous cells of one case
      contained numerous mitochondria. In FISH analysis, many neoplastic cells of both
      cases demonstrated monosomy of chromosomes 15 and 22 and disomy of chromosomes 7
      and 17. One of the two patients died of respiratory failure due to pleuritis
      carcinomatosa 48 months postoperatively. Finally, the pathologist should
      recognize that high grade MTSCC exists despite its rare frequency. FISH analysis
      may be helpful in establishing the diagnosis of this entity. Furthermore, we
      present the first report of a patient with MTSCC dying of distant metastasis.

PMID- 18830938
TI  - Nutritional cellular biomarkers in early life stages of fish.
AB  - Histological (tissular and cellular) indices have a tradition of determining the
      nutritional condition of fish both in the laboratory and in the wild. The
      assessment of condition by means of microscopical methods is probably the mos
      accurate indicator of nutritional status during the early life stages of fish.
      This success is partly attributable large amount of information that can be
      derived from their study and because they are thought to be the only true
      starvation indices. The technique usually consists of the examination of cells
      and organs and the establishment of a grading system based on the
      presence/absence of standardised biomarkers. Each organ is examined, and the
      cellular aspect or tissular cohesion is evaluated qualitatively and even
      quantitatively in order to obtain a measure of the general condition of a larva.
      The literature indicates that there are certain tissular and cellular responses
      to food availability and quality, particularly in the digestive and muscular
      tissues, which are common to most teleost fish larvae. These responses, which are
      independent of water temperature, can be used for assessing fish larvae
      nutritional condition. In this regard, the microscopical organization of the
      liver hepatocytes, the intestinal mucosa, the exocrine pancreas and the muscular
      fibers, which are generally used as target tissues and organs to assess the
      nutritional condition of fish larvae, is deeply reviewed. The advantages and
      disadvantages of the use of different cellular biomarkers of effect are discussed
      considering different conditions.

PMID- 18830939
TI  - The MUC gene family: their role in the diagnosis and prognosis of gastric cancer.
AB  - Early diagnosis of gastric cancer and its differential diagnosis from other non
      malignant gastric diseases like gastritis is still a major clinical problem. Most
      patients are asymptomatic in the early stages of gastric cancer, and there is no
      reliable marker available for the early and specific diagnosis of gastric cancer.
      Many attempts have been made to define the biological profile of gastric cancer
      to improve the chances of its early diagnosis, prognosis and treatment. Several
      studies have shown the aberrant expression profile of mucins in different
      malignancies, suggesting that mucins have a great potential to be used as a
      diagnostic and prognostic marker in gastric cancer. In this review, we have
      briefly described the different types of gastric adenocarcinomas and the
      progression of gastric cancer. Furthermore, the role of mucins and their related
      carbohydrate epitope is discussed in the normal stomach and in the diagnosis and
      prognosis of gastric adenocarcinomas.

PMID- 18830940
TI  - Primordial germ cell specification: the importance of being 'blimped'.
AB  - In mouse embryos, the expression of Blimp1 has recently revealed a population of
      allocated primordial germ cell precursors 24 hours earlier than previously
      thought. Those 'blimped' precursors have been shown to give rise, by mitotic
      division, to germ cells only and no other cell lineages. Here, we try to
      understand the events that lead to Blimp1 expression in the primordial germ cell
      precursors and speculate on what can be the role of Blimp1 during primordial germ
      cell specification and gastrulation in the mouse. Finally, we discuss the
      possible involvement of Blimp1 in the two know modes of germ line segregation
      (epigenesis and preformation).

PMID- 18830942
TI  - Micro- and nanopatterning of spin-transition compounds into logical structures.

PMID- 18830943
TI  - A very simple copper-catalyzed synthesis of anilines by employing aqueous
      ammonia.

PMID- 18830944
TI  - Molecular recognition for high selectivity in carbon nanotube/polythiophene
      chemiresistors.

PMID- 18830945
TI  - MgCl and Mg2Cl2: from theoretical and thermodynamic considerations to
      spectroscopy and chemistry of species with Mg-Mg bonds.

PMID- 18830946
TI  - Molecular dynamics simulations of breathing MOFs: structural transformations of
      MIL-53(Cr) upon thermal activation and CO2 adsorption.

PMID- 18830947
TI  - Chemically triggered biodelivery using metal-organic sol-gel synthesis.

PMID- 18830948
TI  - Evidence for the existence of a terminal imidoscandium compound: intermolecular C
      H activation and complexation reactions with the transient Sc=NAr species.

PMID- 18830949
TI  - A stair-shaped molecular silver(0) chain.

PMID- 18830950
TI  - Peptide fragmentation assisted by surfaces treated with a low-temperature plasma
      in nanoESI.

PMID- 18830951
TI  - Self-assembly of a nanoscopic Pt12Fe12 heterometallic open molecular box
      containing six porphyrin walls.

PMID- 18830952
TI  - A belt-shaped, blue luminescent, and semiconducting covalent organic framework.

PMID- 18830953
TI  - De novo design of a bolaamphiphilic peptide with only natural amino acids.
AB  - A new self-assembling bolaamphiphilic peptide has been designed and synthesized
      using only natural amino acids. This simple peptide is composed of two lysines
      connected by 4-8 alanines to maintain the characteristics of the traditional
      bolaamphiphiles. Based on an irregular secondary structure, it can self-assemble
      into nanospheres, nanorods, or nanofibers with lengths up to micrometers. The
      long nanofibers can be broken into smaller fragments by sonication, however, they
      could reassemble into nanofibers after incubation. Furthermore, the
      nanostructures were shown to have considerable thermostability. This new
      bolaamphiphilic peptide differs from any other self-assembling peptides or
      bolaamphiphiles, and possibly provides a new approach to fabricate nanomaterials.

PMID- 18830954
TI  - Construction of periventricular white matter hyperintensity maps by spatial
      normalization of the lateral ventricles.
AB  - Subcortical and periventricular white matter hyperintensities (WMHs) may have
      different associations with cognition and pathophysiology. The aim of the present
      study is to develop an automated method for construction of periventricular WMH
      maps that enables the analysis of between-group differences in WMH location and
      characteristics in the periventricular region without the requirement of prior
      boundary definition. To avoid influence of WMHs on spatial normalization, a
      reference image of the lateral ventricles was constructed based on images of 24
      subjects. Construction was not biased to a single subject. WMHs were segmented by
      k-nearest neighbor-based classification of magnetic resonance inversion recovery
      and fluid attenuated inversion recovery images. Cerebrospinal fluid segmentations
      of individual subjects were nonrigidly mapped to the reference image of the
      lateral ventricles. The subject's WMHs were transformed to the reference space
      accordingly. Spatial normalization accuracy was validated using measures of
      overlap and of displacement relative to the boundary of the lateral ventricles.
      After spatial normalization, the boundaries of the lateral ventricles closely
      matched the reference image and in an area of approximately 1 cm around the
      lateral ventricles the relative displacement was less than 1 mm. To illustrate
      the method, it was applied to 61 patients with Type 2 diabetes and 26 control
      subjects, whereupon periventricular WMH maps were constructed and compared. The
      proposed method is particularly suited to analyze WMH distribution differences at
      the level of the lateral ventricles between large groups of patients.

PMID- 18830955
TI  - Hierarchical functional modularity in the resting-state human brain.
AB  - Functional magnetic resonance imaging (fMRI) studies have shown that anatomically
      distinct brain regions are functionally connected during the resting state. Basic
      topological properties in the brain functional connectivity (BFC) map have
      highlighted the BFC's small-world topology. Modularity, a more advanced
      topological property, has been hypothesized to be evolutionary advantageous,
      contributing to adaptive aspects of anatomical and functional brain connectivity.
      However, current definitions of modularity for complex networks focus on
      nonoverlapping clusters, and are seriously limited by disregarding inclusive
      relationships. Therefore, BFC's modularity has been mainly qualitatively
      investigated. Here, we introduce a new definition of modularity, based on a
      recently improved clustering measurement, which overcomes limitations of previous
      definitions, and apply it to the study of BFC in resting state fMRI of 53 healthy
      subjects. Results show hierarchical functional modularity in the brain.

PMID- 18830956
TI  - Analyzing brain networks with PCA and conditional Granger causality.
AB  - Identifying directional influences in anatomical and functional circuits presents
      one of the greatest challenges for understanding neural computations in the
      brain. Granger causality mapping (GCM) derived from vector autoregressive models
      of data has been employed for this purpose, revealing complex temporal and
      spatial dynamics underlying cognitive processes. However, the traditional GCM
      methods are computationally expensive, as signals from thousands of voxels within
      selected regions of interest (ROIs) are individually processed, and being based
      on pairwise Granger causality, they lack the ability to distinguish direct from
      indirect connectivity among brain regions. In this work a new algorithm called
      PCA based conditional GCM is proposed to overcome these problems. The algorithm
      implements the following two procedures: (i) dimensionality reduction in ROIs of
      interest with principle component analysis (PCA), and (ii) estimation of the
      direct causal influences in local brain networks, using conditional Granger
      causality. Our results show that the proposed method achieves greater accuracy in
      detecting network connectivity than the commonly used pairwise Granger causality
      method. Furthermore, the use of PCA components in conjunction with conditional
      GCM greatly reduces the computational cost relative to the use of individual
      voxel time series.

PMID- 18830957
TI  - EEG alpha oscillations in the preparation for global and local processing predict
      behavioral performance.
AB  - Visual attention can be directed either to the global features of a display or to
      the local elements that make up the display. We investigated whether oscillatory
      brain responses to globally or locally directed cue stimuli predict behavioral
      performance in subsequent target processing. Induced alpha band (8-12 Hz)
      amplitudes in the pre-stimulus interval were measured separately for the global
      and the local level, where individual trials were assigned to one of three groups
      according to the response speed towards incongruent stimuli. Fast responses to
      local features were associated with high alpha amplitudes in the right centro
      parietal cortex, whereas fast responses to global forms were associated with high
      alpha in left centro-parietal cortex. For trials with slower responses, the
      pattern of hemispheric differences was diminished or even reversed. It is
      interpreted that the left and the right parietal cortex exert top-down control
      over hierarchical processing by inhibiting stimulus representations in one
      hemisphere.

PMID- 18830958
TI  - Rapid and simple method for screening of natural antioxidants from Chinese herb
      Flos Lonicerae Japonicae by DPPH-HPLC-DAD-TOF/MS.
AB  - A rapid and simple method has been developed for the screening and identification
      of natural antioxidants of Flos Lonicerae Japonicae (FLJ), derived from the
      flower buds of Lonicera japonica. The hypothesis is that upon reaction with 1,1
      diphenyl-2-picrylhydrazyl (DPPH), the peak areas (PAs) of compounds with
      potential antioxidant effects in the HPLC chromatograms will be significantly
      reduced or disappeared, and the identity confirmation could be achieved by HPLC
      DAD-TOF/MS hyphenated technique. Using the proposed approach, about 14 compounds
      in the FLJ extract were found to possess a potential antioxidant activity. They
      were identified as chlorogenic acid (1), 1-O-caffeoylquinic acid (1-O-CQA, 2),
      caffeic acid (4), 4-O-CQA (5), rutin (7), isoquercitrin (8), luteolin-7-O
      glucoside (9), lonicerin (10), 4,5-O-dicaffeoylquinic acid (4,5-O-diCQA, 11), 3,5
      O-diCQA (12), 1,3-O-diCQA (13), 3,4-O-diCQA (14), 1,4-O-diCQA (16), and luteolin
      (17). In addition, the free radical scavenging capacities of the available
      identified compounds were also investigated by HPLC assay. The results indicated
      that the compounds with PAs significantly decreasing were natural antioxidants,
      whereas those with PAs not changing presented no activities, which accordingly
      indicated that this newly proposed method could be widely applied for rapid
      screening and identification of natural antioxidants from complex matrices
      including Chinese herbal medicines.

PMID- 18830959
TI  - Removal of envelope protein-free retroviral vectors by anion-exchange
      chromatography to improve product quality.
AB  - We have investigated the role of the retroviral lipid bilayer and envelope
      proteins in the adsorption of retroviral vectors (RVs) to a Fractogel DEAE
      matrix. Intact RVs and their degradation components (envelope protein-free
      vectors and solubilized vector components) were adsorbed to this matrix and
      eluted using a linear gradient. Envelope protein-free RVs (Env(-)) and soluble
      envelope proteins (gp70) eluted in a significantly lower range of conductivities
      than intact RVs (Env(+)) (13.7-30 mS/cm for Env(-) and gp70 proteins vs. 47-80
      mS/cm for Env(+)). The zeta (zeta)-potential of Env(+) and Env(-) vectors was
      evaluated showing that envelope proteins define the pI of the viral particles (pI
      (Env(+)) < 2 versus 3 < pI (Env(-)) < 4) and that Env(+) and Env(-) vectors have
      similar zeta-potentials within pH 5 and 8. The results presented herein indicate
      that the adsorption of retroviral particles occurs through multi-point
      interaction of the envelope proteins with the cationic groups on the
      chromatographic matrix. The strength of this adsorption is thus dependent on the
      amount of envelope protein present in the viral lipid bilayer. In conclusion,
      AEXc enables the separation of gp70 proteins as well as envelope protein-free
      vectors constituting a significant improvement to the quality of retroviral
      preparations for gene therapy applications.

PMID- 18830960
TI  - Analysis of volatiles in dehydrated carrot samples by solid-phase microextraction
      followed by GC-MS.
AB  - A solid-phase microextraction (SPME)-based method for the GC-MS analysis of
      volatiles in dehydrated carrot root samples has been developed and the effect of
      the most important factors (fibre coating, extraction temperature, equilibrium
      time and extraction time) on the fractionation of different volatiles has been
      studied. GC-MS chromatograms showed terpenoids relevant to carrot aroma such as
      alpha-pinene, sabinene, beta-myrcene, limonene, gamma-terpinene, terpinolene,
      trans-caryophyllene and beta-bisabolene, and several furan derivatives whose
      origin is discussed in this paper. As an example of application, this methodology
      has been used for the characterization of volatile composition of industrially
      dehydrated carrots. SPME followed by GC-MS is shown as an affordable, fast and
      solvent-free technique which can be performed with low sample amounts and be
      easily implemented at an industry for quality control purposes.

PMID- 18830961
TI  - Determination of ascorbic acid in human plasma with a view to stability using
      HPLC with UV detection.
AB  - A method for the measurement of ascorbic acid using HPLC with UV detection and
      investigation into the protein precipitation techniques with regard to stability
      and recovery are described. The effectiveness of various protein precipitants was
      tested. Stability of ascorbic acid samples for analysis was investigated over 10
      h. Ascorbic acid samples extracted with metaphosphoric acid were stable on a
      cooled autosampler (4 degrees C) for at least 10 h (with a decline of 1.8% for
      ascorbic acid solution and 2.8% for plasma). Perchloric acid as protein
      precipitant for ascorbic acid was unsuitable (with a decline of 36.0% for
      ascorbic acid solution and 7.3% for plasma). Analytical performance of this
      method is satisfactory. The intra- and interassay coefficients of variation were
      2.1% (n = 10) and 5.8% (n = 12), respectively. The calibration curve was linear
      with the tested range of 2.0-250.0 micromol/L. The recovery was 96.1% with CV =
      4.8% (n = 6) and the LOD was 3 micromol/L. The preliminary reference ranges of
      ascorbic acid in a group of blood donors are 50.8 +/- 22.4 micromol/L. This assay
      is a highly sensitive and reproducible HPLC method for the determination of
      ascorbic acid in human plasma.

PMID- 18830962
TI  - Functionalized-multiwalled carbon nanotubes as a preconcentrating probe for rapid
      monitoring of cationic dyestuffs in environmental water using AP-MALDI/MS.
AB  - A simple and sensitive method was developed for the rapid analysis of cationic
      dyestuffs from river and industrial wastewater using functionalized-multiwalled
      carbon nanotubes (f-MWCNT) with atmospheric pressure-matrix assisted laser
      desorption/ionization mass spectrometry (AP-MALDI/MS). The separation and
      preconcentration of analytes from sample solution was based on electrostatic
      force of attraction between positive dyestuffs and negatively charged f-MWCNT.
      The optimum enrichment of the three dyestuffs was observed at pH 5.0 for 3 min
      contact time and using 1 mg f-MWCNT in 1 mL water sample. The developed method
      has been successfully applied for the determination of three cationic dyestuffs
      namely neutral red (NR), brilliant cresyl blue (BB), and methylene blue (MB) in
      real world samples including river and industrial wastewater. The relative
      recoveries of dyestuffs from water sample were in the range 88.6-98.4%,
      indicating that the matrix had little effect on enrichment of analytes. The LOD
      and LOQ for cationic dyestuffs in water were 0.5-1.9 and 1.6-6.0 microg/L,
      respectively. All the results indicated that the proposed method could be used
      for the simultaneous determination of the three cationic dyestuffs in river and
      industrial wastewater at trace levels without the need of any chromatographic
      separation techniques.

PMID- 18830963
TI  - Analysis of 51 persistent organic pollutants in soil by means of ultrasonic
      solvent extraction and stir bar sorptive extraction GC-MS.
AB  - A novel method based on ultrasonic solvent extraction and stir bar sorptive
      extraction (SBSE) for the analysis of 51 persistent organic pollutants including
      organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), polycyclic
      aromatic hydrocarbons (PAHs), and polybrominated diphenylethers (PBDEs) in soil
      samples was developed. The different parameters that affect both the extraction
      of analytes from the soil samples, such as solvent selection, solvent volume,
      mass of soil, and extraction time, and the partitioning from the solvent/water
      mixture to the PDMS were studied. The final selected conditions consisted of the
      extraction of 1 g of soil with 15 mL methanol by sonication for 30 min. The
      methanol extract was mixed with 85 mL of Milli-Q water and extracted by means of
      SBSE for 14 h at 900 rpm. The stir bars were analyzed by thermal desorption-GC
      mass spectometry (TD-GC-MS). The effects of the matrix on the recovery of the
      various pollutants under the developed method were studied using two soils with
      very different physicochemical properties. Method sensitivity, linearity,
      repeatability, and reproducibility were also studied. Validation and accuracy of
      the method were conducted by analyzing two commercial certified reference
      materials (CRMs). The main advantage of this method resides in the fact that a
      small amount of a nontoxic solvent (methanol) is needed for the extraction of
      only 1 g of solid sample allowing LODs ranging from 0.01 to 2.0 microg/kg.
      Repeatability and reproducibility variations were lower than 20% for all
      investigated compounds. Results of the CRMs verify the high accuracy of this
      method.

PMID- 18830964
TI  - Application of SPE-HPLC-DAD and SPE-TLC-DAD to the determination of pesticides in
      real water samples.
AB  - Planar chromatography with diode array scanning (TLC-DAD) and high-performance
      chromatography with diode array detection (HPLC-DAD) were used to screen water
      samples for pesticides. Pesticides were enriched from lake water samples by SPE
      on C18/SDB-1, C18, C18 Polar Plus and cyanopropyl (CN) cartridges. The recovery
      rates were high for all extraction materials except for all pesticides on CN
      cartridges, for which the values were lower. SPE was used not only for
      preconcentration of analytes but also for their fractionation. The analytes were
      eluted first with methanol and then with dichloromethane. Methanol eluates were
      analysed by HPLC-DAD, the dichloromethane eluates with TLC-DAD. The method was
      validated for precision, repeatability and accuracy. The calibration plots were
      linear between 0.1 and 50.0 microg/mL for all pesticides, the correlation
      coefficients, r, were between 0.9992 and 1.000 as determined by HPLC-DAD. In the
      TLC experiments, the best fit for the calibration lines was found when the
      calibration data were analysed using a second-degree polynomial regression.
      Calibration plots lay between 0.1 and 17 microg/spot for all pesticides, the
      correlation coefficients, r, were between 0.9974 and 0.9997 determined by TLC
      DAD. The LOD was between 0.04 and 0.65 microg/spot (TLC-DAD) and between 0.02 and
      3.68 microg/mL (HPLC-DAD).

PMID- 18830966
TI  - Antiobesity effects of wild ginseng (Panax ginseng C.A. Meyer) mediated by PPAR
      gamma, GLUT4 and LPL in ob/ob mice.
AB  - The antiobesity effect of wild ginseng (WG; Panax ginseng C.A. Meyer) in male
      obese leptin-deficient (B6.V-Lepob, 'ob/ob') mice was evaluated. WG was
      administered orally to mice at doses of 100 mg/kg and 200 mg/kg daily for 4
      weeks. The WG-treated ob/ob mice showed a loss of body weight and a decrease in
      blood glucose levels compared with control mice. WG regulated the mRNA expression
      level especially, it increased peroxisome proliferators-activated receptors-gamma
      (PPAR-gamma) and lipoprotein lipase (LPL) in adipose tissue, as well as glucose
      transporter 4 (GLUT4) and insulin receptor (IR) in the skeletal muscle and liver.
      Taken together, these results suggest that WG may play a vital role in the
      antiobesity effect in ob/ob mice; this has importance in insulin sensitivity.
      This may prove to be of clinical importance in improving the management of
      obesity and related metabolic syndromes.

PMID- 18830967
TI  - Production, partial purification and characterization of feruloyl esterase by
      Aspergillus awamori in submerged fermentation.
AB  - Microbial feruloyl esterases acting on plant cell wall polymers represent key
      tools for the degradation of plant cell wall. In this paper, we describe in
      detail the microbial production, partial purification and characterization of
      feruloyl esterase from a culture medium of Aspergillus awamori strain IFO4033
      obtained from a crude hemicellulose preparation of wheat straw, corncobs and
      wheat germ. Feruloyl esterase was extracted using centrifugation and dialysis,
      and then purified by ion exchange chromatography and microfiltration to
      homogeneity, which was checked by SDSPAGE and isoelectric focusing-PAGE. Protein
      content and activity of the enzyme were measured in each step of extraction and
      purification. Biomass was determined by the dry weight method. pH and temperature
      optima of feruloyl esterase enzyme were also determined. The effects of culturing
      time, and carbon and nitrogen sources on enzyme production were systematically
      investigated. Finally, enzyme activities under different storage conditions were
      examined.

PMID- 18830968
TI  - Inhibition of microsomal triglyceride transfer protein expression and atherogenic
      risk factor apolipoprotein B100 secretion by tanshinone IIA in HepG2 cells.
AB  - Salvia miltiorrhiza Bunge is known to be effective for the treatment of
      cardiovascular diseases. Here, we have isolated tanshinone IIA (T-IIA) from S.
      miltiorrhiza Bunge. The aim of this study is to address the mechanisms where
      apolipoprotein B-100 (ApoB) regulation is associated with T-IIA, since T-IIA
      regulates the lipoprotein metabolism in liver cells. Human HepG2 cells treated
      with T-IIA for 24 h exerted a dose-dependent inhibitory effect on ApoB secretion
      together with triglyceride. However, another secretory protein, albumin, was
      unaffected by T-IIA treatment, indicating that the effect of T-IIA is specific
      for ApoB secretion. T-IIA decreased the transcription level of microsomal
      triglyceride transfer protein gene, suggesting that lipoprotein assembly is
      likely to be involved in the inhibited ApoB secretion. Interestingly, T-IIA
      inhibited ApoB secretion via a proteasome-dependent pathway. Our results suggest
      that T-IIA is an influential inhibitor of ApoB secretion and triglyceride
      secretion in liver cells.

PMID- 18830969
TI  - Gene delivery into hepatocytes with the preS/liposome/DNA system.
AB  - Gene delivery into human hepatocytes remains a critical issue for the development
      of liver-directed gene therapy. Gene delivery based on non-viral vectors is an
      attractive approach relative to viral vectors. In this report, novel delivery
      system of preS/liposome/DNA virus-like particle (VLP) was developed for gene
      transfection into hepatocytes in vivo and in vitro. Plasmid pCMVbeta, expressing
      beta-galactosidase, was encapsulated with cationic liposome, and then the
      histidine-tagged preS domain of hepatitis B virus was coated on the surface of
      liposome/DNA to form preS/liposome/ DNA VLP. Transfection efficiencies of
      preS/liposome/DNA, liposome/DNA, naked DNA and preS were analyzed using several
      different human cell lines. The highest transfection efficiency was found using
      preS/liposome/DNA VLP as the transfection reagent in human hepatocyte (HH) cell
      line. Results show that preS domain of hepatitis B virus coated on liposome/DNA
      can be used for highly efficient gene transfection into human hepatocytes.
      Moreover, the target characteristic of preS/liposome/DNA was analyzed in vivo.
      After preS/liposome/DNA VLP was injected into immunocompromised (Nude) mice via
      the tail vein, most of beta-galactosidase was expressed in the liver; however, no
      significant target expression was found with the injection of liposome/ DNA or
      naked DNA. Our results show that preS/liposome/DNA VLP can be used as a novel
      liver-specific gene delivery system.

PMID- 18830970
TI  - A guide to the integrated application of on-line data mining tools for the
      inference of gene functions at the systems level.
AB  - Genes function in networks to achieve a common biological response. Thus,
      inferences into the biological role of individual genes can be gained by
      analyzing their association with other genes with more precisely defined
      functions. Here, we present a guide, using the well-characterized Arabidopsis
      thaliana pathogenesis-related protein 2 gene (PR-2) as an example, to document
      how the sequential use of web-based tools can be applied to integrate information
      from different databases and associate the function of an individual gene with a
      network of genes and additionally identify specific biological processes in which
      they collectively function. The analysis begins by performing a global expression
      correlation analysis to build a functionally associated gene network. The network
      is subsequently analyzed for Gene Ontology enrichment, stimuli and mutant
      specific transcriptional responses and enriched putative promoter regulatory
      elements that may be responsible for their correlated relationships. The results
      for the PR-2 gene are entirely consistent with the published literature
      documenting the accuracy of this type of analysis. Furthermore, this type of
      analysis can also be performed on other organisms with the appropriate data
      available and will greatly assist in understanding individual gene functions in a
      systems context.

PMID- 18830971
TI  - Epitaxial nanodot arrays of transition-metal oxides fabricated by dry deposition
      combined with a nanoimprint-lithography-based molybdenum lift-off technique.

PMID- 18830972
TI  - GSH-dependent iNOS and HO-1 mediated apoptosis of human Jurkat cells induced by
      nickel(II).
AB  - The molecular mechanisms by which nickel compounds cause immune cytotoxicity are
      far from understood. Our preliminary data suggested that nickel(II) induced
      apoptosis in Jurkat cells by mitochondrial pathway, specifically via
      mitochondrial membrane potential dissipation and antiapoptotic gene bcl-2 down
      regulation. The main goal of this study was to further investigate the toxicity
      of nickel, especially the induction of reactive oxygen species (ROS) on immune
      cells, which finally induced apoptosis. Nickel was found to induce glutathione
      (GSH) depletion in a dose- and time-dependent manner. When Jurkat cells were
      preincubated with antioxidant N-acetylcysteine (NAC), apoptosis was inhibited
      distinctly, which suggested that ROS played an initial role in nickel immune
      toxicity. Heme oxygenase-1 (HO-1) and Nitric oxide (NO) which may play an
      important role in regulatory and protective processes in cells were assayed upon
      nickel treatment. A significant increase in HO-1 mRNA levels was detected in
      nickel treated cells. We confirmed that reduction of Nitrate levels in Jurkat
      cells was due to down-regulation of inducible nitric oxide synthase (iNOS), not
      endothelial nitric oxide synthase (eNOS). Expression changes of HO-1 and iNOS
      were markedly blocked when Jurkat cells were preincubated with NAC, suggesting
      that ROS resulted in HO-1 and iNOS dysfunction in Jurkat cells. We supposed that
      the immune toxicity of nickel(II) was mainly due to GSH depletion and finally led
      to apoptosis, probably via changing the expression levels of HO-1 and iNOS in
      human T lymphocytes.

PMID- 18830973
TI  - New adaptive chiral thiophene ligands for copper-catalyzed asymmetric Henry
      reaction.
AB  - A new type of adaptive chiral thiophene-based ligands 3 has been designed and
      developed. The synthetic flexibility of the thienyl ring allowed for the
      preparation of polydendate C2-symmetric ligands in good yields, carrying
      simultaneously "hard" as well as "soft" coordinating atoms (i.e., N, S). The
      coordination attitude of 3 was then tested in the enantioselective base-free
      Cu(OAc)(2)-catalyzed addition of nitromethane to aromatic aldehydes, leading to
      the corresponding beta-nitro alcohols in excellent yields and enantiomeric
      excesses up to 86%.

PMID- 18830974
TI  - A novel electrosynthetic system for anodic substitution reactions by using
      parallel laminar flow in a microflow reactor.
AB  - We have developed a novel electrosynthetic system for anodic substitution
      reactions by using parallel laminar flow in a microflow reactor. This system
      enables nucleophilic reactions to overcome the restraint, such as the oxidation
      potential of nucleophiles and the stability of cationic intermediates, by the
      combined use of ionic liquids as reaction media and the parallel laminar flow in
      the microflow reactor. By using this novel electrosynthetic system, the anodic
      substitution reaction of carbamates, especially of cyclic carbamates, with
      allyltrimethylsilane were carried out to provide the corresponding products in
      moderate to good conversion yields in a single flow-through operation at ambient
      temperature (without the need for low-temperature conditions).

PMID- 18830975
TI  - Noduliprevenone: a novel heterodimeric chromanone with cancer chemopreventive
      potential.

PMID- 18830976
TI  - Highly enantioselective synthesis of beta-amino acid derivatives by the lewis
      base catalyzed hydrosilylation of beta-enamino esters.

PMID- 18830977
TI  - Supramolecular helical fluid columns from self-assembly of homomeric dipeptides.
AB  - Herein, we demonstrate that with the widespread theme of residue patterning and
      stereochemical restraints of self-complimenting proteinogenic amino acids, a new
      and rich class of homomeric dipeptides exhibiting two-dimensional fluid
      aggregates with hierarchical ordering can be obtained. In particular, a simple
      way of achieving a class of functional dipeptides, wherein the first and the
      second residues chosen are L-/D-alanines and L-/D-leucines, has been
      accomplished. The supramolecules synthesized can be regarded as intermediates
      between polycatenars and taper-shaped amphiphiles because they possess two
      lipophilic segments interlinked by a peptide unit (spacer). Two pairs of
      enantiomers and their respective diastereomers derived from these amino acids are
      evidenced to self-organize into a helical columnar phase through hydrogen bonding
      by means of FTIR, UV/Vis, and chiroptical circular dichroism (CD) spectral
      analyses as well as by optical, calorimetric, electrical switching, and X-ray
      studies. The CD and X-ray studies have revealed that the form chirality
      (handedness) and the magnitude of out-of-plane fluctuations of the lattice planes
      of the fluid supramolecular columnar structures are solely directed by the
      stereochemistry encoded in the spacer. Of special significance, the less
      frequently found oblique helical columnar phase formed by a pair of enantiomers
      derived from L-/D-alanines, unlike those derived from other amino acids, exhibit
      ferroelectric behavior; the measured spontaneous polarization is as high as 440
      nC cm(-2). Besides, all these supramolecules form stable organogels in ethanol
      and the CD and SEM studies on a representative gel suggest the presence of
      helical structures.

PMID- 18830978
TI  - Efficient synthesis of chromone and flavonoid derivatives with diverse
      heterocyclic units.
AB  - Chromones and flavonoids are important bioactive compounds. We envisioned that
      new heterocyclic-substituted chromones or flavonoids might act as new bioactive
      compounds. To obtain diverse molecules, we developed an efficient one-pot
      synthesis by Michael aldol reaction of chromone and flavonoid derivatives bearing
      heterocyclic units. The 2,3-heterocyclic-substituted chromones were obtained in
      one step. Moreover, the use of substituted benzaldehydes and subsequent addition
      of heterocyclic aldehydes gave 3-pyridyl-substituted flavones. We also examined
      these one-pot reactions in the solid phase. To introduce an additional point of
      diversity into the molecules, Suzuki-Miyaura coupling was performed. Furthermore,
      we identified the cytotoxicity of the synthesized compounds against cancer cells
      (PANC1 and HeLa cells). Several compounds were cytotoxic to these cancer cells.

PMID- 18830979
TI  - Photodynamic activity of C70 caged within surface-cross-linked liposomes.
AB  - [70]Fullerene (C(70)) encapsulated into a surface-cross-linked liposome, a so
      called cerasome, was prepared by an exchange reaction incorporating C(70)gamma
      cyclodextrin complexes into lipid membranes. Fullerene exchange in a cerasome
      incorporated C(70) (CIC(70)), as well as in a lipid-membrane-incorporated C(70)
      (LMIC(70)), was completed within 1 min with stirring at 25 degrees C. CIC(70) was
      more resistant to lysis than LMIC(70) towards lysing agents such as surfactants.
      Furthermore, the photodynamic activity of CIC(70) in HeLa cells was similar to
      that of LMIC(70), indicating that C(70) can act as a photosensitizing drug (PS)
      without release from cerasome membranes. Thus, in contrast with general drug
      delivery systems (DDSs), which require the drug to be released from the interior
      of liposomes, carriers for PSs for use in photodynamic therapy (PDT) do not
      necessarily need to release the drug. These results indicate that DDSs with high
      morphological stability can increase the residence time in blood and achieves
      tumor-selective drug delivery by the enhanced permeability and retention (EPR)
      effect.

PMID- 18830980
TI  - The pH effect on the naphthoquinone-photosensitized oxidation of 5
      methylcytosine.
AB  - The pH effect on the one-electron photooxidation of 5-methyl-2'-deoxycytidine
      (d(m)C) by sensitization with 2-methyl-1,4-naphthoquinone (NQ) was investigated.
      Photoirradiation of an aqueous solution containing d(m)C and NQ under slightly
      acidic conditions of pH 5.0 efficiently produced 5-formyl-2'-deoxycytidine,
      whereas similar NQ-photosensitized oxidation of d(m)C proceeded to a lesser
      extent under more acidic or basic conditions. Fluorescence-quenching experiments
      revealed that the less-efficient photooxidation at pH values below 4.5 is
      attributed to the decreased rate of one-electron oxidation of d(m)C owing to
      protonation at the N(3)-position. The NQ-photosensitized oxidation of an N(4)
      dimethyl-substituted d(m)C derivative under various pH conditions also suggests
      that the pH change in the range of 5.0 to 8.0 may be responsible for a reversible
      deprotonation-protonation equilibrium at the N(4)-exocyclic amino group of the
      d(m)C radical cation. In accord with the photochemical reactivity of monomeric
      d(m)C, the 5-methylcytosine residue in oligodeoxynucleotides was oxidized
      efficiently by photoexcited NQ-tethered oligodeoxynucleotides under slightly
      acidic conditions to form an alkali-labile 5-formylcytosine residue.

PMID- 18830981
TI  - The role of noninnocent solvent molecules in organocatalyzed asymmetric Michael
      addition reactions.
AB  - A proline-catalyzed asymmetric Michael addition between ketones and trans-beta
      nitrostyrene was studied by using the density-functional theory with mPW1PW91 and
      B3LYP functionals. Improved insight into the enantio- and diastereoselective
      formation of gamma-nitroketones/-aldehydes is obtained through transition-state
      analysis. Consideration of the activation parameters obtained from gas-phase
      calculations and continuum solvation models failed to reproduce the reported
      experimental stereoselectivities for the reaction between cyclohexanone and 3
      pentanone with trans-beta-nitrostyrene. The correct diastereo- and
      enantioselectivites were obtained only upon explicit inclusion of solvent
      molecules in the diastereomeric transition states that pertain to the C--C bond
      formation. Among the several transition-state models that were examined, the one
      that exhibits cooperative hydrogen-bonding interactions with two molecules of
      methanol could explain the correct stereochemical outcome of the Michael
      reaction. The change in differential stabilization that arises as a result of
      electrostatic and hydrogen-bonding interactions in the key transition states is
      identified as the contributing factor toward obtaining the correct diastereomer.
      This study establishes the importance of including explicit solvent molecules in
      situations in which the gas-phase and continuum models are inadequate in
      obtaining meaningful insight regarding experimental stereoselectivities.

PMID- 18830982
TI  - Facile high-yield synthesis of polyaniline nanosticks with intrinsic stability
      and electrical conductivity.
AB  - Chemical oxidative polymerization at 15 degrees C was used for the simple and
      productive synthesis of polyaniline (PAN) nanosticks. The effect of
      polymerization media on the yield, size, stability, and electrical conductivity
      of the PAN nanosticks was studied by changing the concentration and nature of the
      acid medium and oxidant and by introducing organic solvent. Molecular and
      supramolecular structure, size, and size distribution of the PAN nanosticks were
      characterized by UV/Vis and IR spectroscopy, X-ray diffraction, laser particle
      size analysis, and transmission electron microscopy. Introduction of organic
      solvent is advantageous for enhancing the yield of PAN nanosticks but
      disadvantageous for formation of PAN nanosticks with small size and high
      conductivity. The concentration and nature of the acid medium have a major
      influence on the polymerization yield and conductivity of the nanosized PAN. The
      average diameter and length of PAN nanosticks produced with 2 M HNO(3) and 0.5 M
      H(2)SO(4) as acid media are about 40 and 300 nm, respectively. The PAN nanosticks
      obtained in an optimal medium (i.e., 2 M HNO(3)) exhibit the highest conductivity
      of 2.23 S cm(-1) and the highest yield of 80.7 %. A mechanism of formation of
      nanosticks instead of nanoparticles is proposed. Nanocomposite films of the PAN
      nanosticks with poly(vinyl alcohol) show a low percolation threshold of 0.2 wt %,
      at which the film retains almost the same transparency and strength as pure
      poly(vinyl alcohol) but 262 000 times the conductivity of pure poly(vinyl
      alcohol) film. The present synthesis of PAN nanosticks requires no external
      stabilizer and provides a facile and direct route for fabrication of PAN
      nanosticks with high yield, controllable size, intrinsic self-stability, strong
      redispersibility, high purity, and optimizable conductivity.

PMID- 18830983
TI  - One-pot catalytic enantioselective domino nitro-michael/michael synthesis of
      cyclopentanes with four stereocenters.
AB  - A highly enantioselective organocatalytic one-pot synthesis of nitro-, formyl-,
      and ester-functionalized cyclopentanes with four stereocenters is presented. The
      cyclopentanes were formed as a predominant diasteroisomer and isolated in high
      yields with 97-99 % ee.

PMID- 18830984
TI  - Synthesis of diaminopimelic acid containing peptidoglycan fragments and tracheal
      cytotoxin (TCT) and investigation of their biological functions.
AB  - Bacterial cell wall peptidoglycan (PGN) is a potent immunostimulator and immune
      adjuvant. The PGN of Gram-negative bacteria and some Gram-positive bacteria
      contain meso-diaminopimelic acid (meso-DAP), and we have recently shown that the
      intracellular protein Nod1 is a PGN receptor and recognizes DAP-containing
      peptides. In this study, we achieved the synthesis of DAP-containing PGN
      fragments, including the first chemical synthesis of tracheal cytotoxin (TCT),
      GlcNAc-(beta1-4)-(anhydro)MurNAc-L-Ala-gamma-D-Glu-meso-DAP-D-Ala, and a
      repeating-unit of DAP-type PGN, GlcNAc-(beta1-4)-MurNAc-L-Ala-gamma-D-Glu-meso
      DAP-D-Ala. For the synthesis of PGN fragments, we first established a new
      synthetic method for an orthogonally protected meso-DAP derivative, and then we
      constructed the glycopeptide structures. The ability of these fragments to
      stimulate human Nod1, as well as differences in Nod1 recognition of the variety
      of synthesized ligand structures were examined. The results showed that the
      substitution of the N terminus of iE-DAP is necessary for stronger Nod1
      recognition, but the structure of the substituent seems not to be strictly
      recognized. The importance of the carboxyl group at the 2-position of DAP for
      human Nod1 stimulation was also shown.

PMID- 18830985
TI  - Use of Raman spectroscopy as an in situ tool to obtain kinetic data for organic
      transformations.
AB  - Raman spectroscopy has been used as an in situ tool to obtain kinetic data for an
      organic transformation. The model reaction studied was the synthesis of 3
      acetylcoumarin from the condensation between salicylaldehyde and ethyl
      acetoacetate with piperidine as a catalyst. The study shows that precise kinetic
      data can be obtained quickly and reproducibly, allowing for the facile
      determination of both overall reaction order and reaction order with respect to
      each component of the reaction. Additionally, Arrhenius parameters such as
      activation energy for a reaction can be readily obtained. In conjunction with
      computational modeling, this data-rich analysis technique also allows for in
      depth probing of mechanistic aspects of reactions. Microwave heating proves to be
      an ideal tool for aiding in kinetic studies. It offers reproducible noncontact
      heating as well as precise temperature monitoring and data recording.

PMID- 18830986
TI  - The dimeric "hand-shake" motif in complexes and metallo-supramolecular assemblies
      of cyclotriveratrylene-based ligands.
AB  - A series of clathrate and metal complexes with cyclotriveratrylene-like molecular
      host ligands show a similar dimeric homomeric inclusion motif in which a ligand
      arm of one host is the intra-cavity guest of another and vice versa. This "hand
      shake" motif is found in the trinuclear transition metal complex
      [Cu(3)Cl(6)(1)]CH(3)CN1.5 H(2)O in which 1 is tris(4-[2,2',6',2''
      terpyridyl]benzyl)cyclotriguaiacylene; in the self-included M(4)L(4) tetrahedral
      metallo-supramolecular assembly [Ag(4)(2)(4)] (BF(4))(4) in which 2 is tris-(2
      quinolylmethyl)cyclotriguaiacylene; in the 1D coordination chains [Ag(4)]ReO(4)
      CH(3)CN and [Ag(5)]SbF(6)3 DMFH(2)O in which 4 is tris(1H-imidazol-1
      yl)cyclotriguaiacylene and 5 is tris{4-(2-pyridyl)benzyl}cyclotriguaiacylene; and
      in the acetone clathrate of tris{4-(2-pyridyl)benzyl-amino}cyclotriguaiacylene.
      Clathrates of ligands 2 and 5 do not show the same dimeric motif, although 2 has
      an extended homomeric inclusion motif that gives a hexagonal network.

PMID- 18830987
TI  - Towards the IR limit of the triplet-triplet annihilation-supported up-conversion:
      tetraanthraporphyrin.

PMID- 18830988
TI  - Functionalised saturated-backbone carbene ligands: yttrium and uranyl alkoxy
      carbene complexes and bicyclic carbene-alcohol adducts.
AB  - A new and modular route to bidentate ligands that combines an alkoxide with a
      saturated backbone N-heterocyclic carbene (NHC) is presented. The
      bi(heterocyclic) compounds are formally the addition product of a saturated NHC
      and the alcohol group of the N-functionalised arm. Using these compounds, the
      synthesis and structural characterisation of the first electropositive metal
      complexes of saturated N-heterocyclic carbenes has been achieved, and examples
      structurally characterised for the yttrium(III) and the uranyl [UO(2)](2+)
      cations.

PMID- 18830989
TI  - On the nature of organoindium intermediates: the formation of readily isolable
      difluoropropargylindium reagents and their regioselectivity towards electrophilic
      substitutions.
AB  - The structure and reactivity of intermediate propargylindium complexes have been
      investigated. Their reaction with electrophiles produced a difluoroalkyne or 
      allene, depending on the nature of the electrophiles. A mechanism based on the
      Curtin-Hammett principle was invoked to explain this phenomenon. A newly proposed
      mechanism on the formation of indium(III) complexes, through the intermediacy of
      indium(I) species, could help to explain the reaction of indium with 1,1,1
      difluorobromo-2-alkynes in the presence of aldehydes.

PMID- 18830990
TI  - Intramolecular 1,8-hydrogen-atom transfer reactions in (1-->4)-O-disaccharide
      systems: conformational and stereochemical requirements.
AB  - The stereochemical and conformational factors controlling the intramolecular
      hydrogen-atom transfer (HAT) reaction between the two pyranose units in a (1-->4)
      O-disaccharide when promoted by a primary 6-O-yl radical are studied. Models with
      alpha-D-Glcp-(1-->4)-beta-D-Glcp, alpha-L-Rhamp-(1-->4)-alpha-D-Galp or alpha-D
      Manp-(1-->4)-beta-L-Gulp skeletons led exclusively to the abstraction of the
      hydrogen from H--C-5' and the formation, through a nine-membered transition
      state, of a 1,3,5-trioxocane ring system in a stable boat-chair conformation.
      Notwithstanding, derivatives of alpha-L-Rhamp-(1-->4)-alpha-D-Glcp or alpha-D
      Manp-(1-->4)-alpha-D-Galp exclusively abstract the hydrogen from H--C-1' through
      a seven-membered transition state and, therefore, lead to an interglycosidic
      spiro ortho ester.

PMID- 18830991
TI  - Organocatalytic approach to benzofused nitrogen-containing heterocycles:
      enantioselective total synthesis of (+)-angustureine.

PMID- 18830993
TI  - Reconstitution and anchoring of cytoskeleton inside giant unilamellar vesicles.
AB  - Among the requirements for all life forms is the ability to self-replicate. In
      eukaryotic cellular systems, this division is achieved through cytokinesis, and
      is facilitated by the (re)arrangement and interaction of cytoskeletal proteins
      with lipids and other proteins localized to the plasma membrane. A fascinating
      challenge of modern synthetic biology is the bottom-up reconstitution of such
      processes for the generation of an artificial cell. One crucial step towards this
      goal is the functional reconstitution of the protein-anchoring machinery to
      facilitate cytokinesis into lipid vesicles. True to the ideal of a minimal cell
      like system, we here describe the formation of an actin-based cytoskeleton within
      giant unilamellar vesicles (GUVs) made from porcine brain lipid extracts. We
      demonstrate that the actin filaments are localised and anchored to the interior
      walls of the GUVs through the spectrin/ankyrin proteins, and produce tightly
      packed actin bundles. These studies allow for the examination of cytoskeletal
      rearrangements within a cell-like model membrane system and represent important
      first steps in reconstituting the minimal machinery required for the division of
      an artificial cell. In addition, the study of such minimal systems can shed light
      on protein functions that are commonly unobservable or hidden within the
      overwhelming complexity of cells.

PMID- 18830994
TI  - Structural characteristics of hydrogenated carbon and boron nitride nanotubes:
      impact of H-H interactions.
AB  - The structural characteristics of perhydrogenated carbon and boron nitride
      nanotubes are determined by means of quantum chemical calculations. Two families
      of nanotubes are systematically studied for both carbon and boron nitride, the
      nanotubes being derived from the perhydrogenated (110) and (111) sheets of
      diamond and cubic boron nitride. Single-walled perhydrogenated carbon nanotubes
      prefer structures analogous to the (111) sheet. In clear contrast, the single
      walled perhydrogenated boron nitride nanotubes prefer structures analogous to the
      (110) sheet. The significantly different structural characteristics are due to
      the polarization of hydrogen atoms in the perhydrogenated boron nitride
      nanotubes. The presence of attractive electrostatic H--H interactions leads to a
      strong preference for multilayering of the boron nitride sheets and nanotubes.
      The results are expected to provide new insights into the structural
      characteristics of main-group binary hydrides.

PMID- 18830995
TI  - Picosecond structural relaxation of abietic acid based amine end capped para
      phenylenevinylene trimers in solution.
AB  - The synthesis and photophysical properties of six new abietic acid based amine
      end-capped p-phenylenevinylene trimers (AECPV3) in their lowest excited singlet
      states are presented. The AECPV3 compounds show a large red-shift of both the
      absorption (25-30 nm) and emission (37-42 nm) maxima with respect to those of the
      corresponding trimers. Picosecond time-resolved fluorescence data reveal the
      presence of a fast conformational relaxation process (40-62 ps) of the initially
      excited compounds, leading to more planar conformers. The conformational
      relaxation time is proportional to the volume of both the side chain and the
      amine groups.

PMID- 18830996
TI  - Fatty acid synthase is up-regulated during hepatitis C virus infection and
      regulates hepatitis C virus entry and production.
AB  - Hepatitis C virus (HCV) is a major human pathogen that causes serious illness,
      including acute and chronic hepatitis, cirrhosis, and hepatocellular carcinoma.
      Using a mass spectrometry-based proteomics approach, we have identified 175
      proteins from a cell culture supernatant fraction containing the HCV genotype 2a
      (JFH1) virus, among which fatty acid synthase (FASN), the multifunctional enzyme
      catalyzing the de novo synthesis of fatty acids, was confirmed to be highly
      enriched. Subsequent studies showed that FASN expression increased in the human
      hepatoma cell line, Huh7, or its derivative, upon HCV infection. Blocking FASN
      activity by C75, a pharmacological FASN inhibitor, led to decreased HCV
      production. Reduction of FASN by RNA interference suppressed viral replication in
      both replicon and infection systems. Remarkably, FASN appeared to be selectively
      required for the expression of claudin-1, a tight junction protein that was
      recently identified as an entry coreceptor for HCV, but not for the expression of
      another HCV coreceptor, CD81. The decrease in Claudin-1 expression resulting from
      FASN inhibition was accompanied by a decrease in transepithelial electric
      resistance of Huh7 cells, implying a reduction in the relative tightness of the
      cell monolayer. Consequently, the entry of human immunodeficiency virus-HCV
      pseudotypes was significantly inhibited in C75-treated Huh7 cells. CONCLUSION: As
      far as we know, this is the first line of evidence that demonstrates that HCV
      infection directly induces FASN expression, and thus suggests a possible
      mechanism by which HCV infection alters the cellular lipid profile and causes
      diseases such as steatosis.

PMID- 18830997
TI  - Inhibitory kinetics of beta-N-acetyl-D-glucosaminidase from prawn (Litopenaeus
      vannamei) by zinc ion.
AB  - Prawn (Litopenaeus vannamei) beta-N-acetyl-D-glucosaminidase (NAGase, EC
      3.2.1.52) is involved in the digestion and molting processes. Zinc is one of the
      most important metals often found in the pollutant. In this article, the effects
      of Zn(2+) on prawn NAGase activity for the hydrolysis of pNP-NAG have been
      investigated. The results showed that Zn(2+) could reversibly and
      noncompetitively inhibit the enzyme activity at appropriate concentrations and
      its IC(50) value was estimated to be 6.00 +/- 0.25 mM. The inhibition model was
      set up, and the inhibition kinetics of the enzyme by Zn(2+) has been studied
      using the kinetic method of the substrate reaction. The inhibition constant was
      determined to be 11.96 mM and the microscopic rate constants were also determined
      for inactivation and reactivation. The rate constant of the inactivation (k(+0))
      is much larger than that of the reactivation (k(-0)). Therefore, when the Zn(2+)
      concentration is sufficiently large, the enzyme is completely inactivated. On
      increasing the concentration of Zn(2+), the fluorescence emission peak and the UV
      absorbance peak are not position shifted, but the intensity decreased, indicating
      that the conformation of Zn(2+)-bound inactive NAGase is stable and different
      from that of native NAGase. We presumed that Zn(2+) made changes in the activity
      and conformation of prawn NAGase by binding with the histidine or cysteine
      residues of the enzyme.

PMID- 18830998
TI  - The neural correlates of recollection: hippocampal activation declines as
      episodic memory fades.
AB  - Memories for certain events tend to linger in rich, vivid detail, and retrieval
      of these memories includes a sense of re-experiencing the details of the event.
      Most events, however, are not retained in any detailed way for more than a few
      days. According to one theory, the hippocampus plays a specific role in
      supporting episodic retrieval, that is, the re-experiencing of an event as part
      of one's personal past. This theory predicts that as episodic memories fade over
      time and are reduced to feelings of familiarity, activity in the hippocampus
      should no longer be associated with retrieval. We used high-resolution functional
      imaging to explore neural activity in medial temporal lobe subregions while
      participants performed a recognition task at both a short (10-min) and long (1
      week) study-test delay. For each recognized item, subjects made "Remember/Know"
      judgments, allowing us to distinguish between items that were consistently
      episodic across the two tests and items that were initially episodic, but later
      became merely familiar. Our results demonstrate that activity in the subiculum is
      specifically associated with episodic recollection. Overall, recollected items
      were associated with higher activity in the subiculum than other items. For
      transiently recollected items, there was a decrease in subicular activity across
      the 1-week delay as memory faded from recollection to familiarity, whereas
      consistently recollected items were associated with enhanced subicular activity
      at both delays. These results provide evidence of a link between subicular
      activation and recollective experience.

PMID- 18830999
TI  - Quantitative transcriptional neuroanatomy of the rat hippocampus: evidence for
      wide-ranging, pathway-specific heterogeneity among three principal cell layers.
AB  - We have used laser-capture microdissection and microarray hybridization to
      characterize gene expression in the three principal neuron layers of rat
      hippocampus. Correlative and clustering analyses revealed all three layers to be
      easily differentiated from one another based on gene expression profile alone. A
      greater disparity in gene expression exists between dentate granule and pyramidal
      cell layers, reflecting phenotypic and ontological differences between those cell
      populations. Remarkably, the level of more than 45% of expressed transcripts was
      significantly different among the three neuron populations, with more than a
      third of those (>1,000 transcripts) being at least twofold different between
      layers. Even CA1 and CA3 pyramidal cell layers were dramatically different on a
      transcriptional level with a separate analysis indicating that nearly 20% of
      transcripts are differentially expressed between them. Only a small number of
      transcripts were specific for a given hippocampal cell layer, suggesting that
      functional differences are more likely secondary to wide-ranging expression
      differences of modest magnitude rather than very large disparities in a few
      genes. Categorical analysis of transcript abundance revealed concerted
      differences in gene expression among the three cell layers referable to specific
      cellular pathways. For instance, transcripts encoding proteins involved in
      glucose metabolism are most highly expressed in the CA3 pyramidal layer, which
      may reflect an underlying greater metabolic rate of these neurons and partially
      explain their exquisite vulnerability to seizure-induced damage. Conversely,
      transcripts related to MAP kinase signaling pathways and transcriptional
      regulator activity are prominent in the dentate granule cell layer, which could
      contribute to its resistance to damage following seizure activity by positioning
      these neurons to respond to external stimuli by altering transcription. Taken
      together, these data suggest that unique physiological characteristics of major
      cell layers, such as neuronal activity, neuronal plasticity, and vulnerability to
      neurodegeneration, are reflected in substantial transcriptional heterogeneity
      within the hippocampus.

PMID- 18831001
TI  - In situ product recovery of n-butanol using polymeric resins.
AB  - Polymeric resins with high n-butanol adsorption affinities were identified from a
      candidate pool of commercially available materials representing a wide array of
      physical and chemical properties. Resin hydrophobicity, which was dictated by the
      chemical structure of its constituent monomer units, most greatly influenced the
      resin-aqueous equilibrium partitioning of n-butanol whereas ionic
      functionalization appeared to have no effect. In general, those materials derived
      from poly(styrene-co-divinylbenzene) possessed the greatest n-butanol affinity,
      while the adsorption potential of these resins was limited by their specific
      surface area. Resins were tested for their ability to serve as effective in situ
      product recovery (ISPR) devices in the n-butanol fermentation by Clostridium
      acetobutylicum ATCC 824. In small-scale batch fermentations, the addition of 0.05
      kg/L Dowex Optipore SD-2 facilitated achievement of effective n-butanol titers as
      high as 2.22% (w/v), well above the inhibitory threshold of C. acetobutylicum
      ATCC 824, and nearly twice that of traditional, single-phase fermentations.
      Retrieval of n-butanol from resins via thermal treatment was demonstrated with
      high efficiency and predicted to be economically favorable. Due to its modular
      nature, the proposed ISPR design exhibits strong potential for compatibility with
      future n-butanol fermentation efforts.

PMID- 18831000
TI  - Contributions of the hippocampus and medial prefrontal cortex to energy and body
      weight regulation.
AB  - The effects of selective ibotenate lesions of the complete hippocampus (CHip),
      the hippocampal ventral pole (VP), or the medial prefrontal cortex (mPFC) in male
      rats were assessed on several measures related to energy regulation (i.e., body
      weight gain, food intake, body adiposity, metabolic activity, general behavioral
      activity, conditioned appetitive responding). The testing conditions were
      designed to minimize the nonspecific debilitating effects of these surgeries on
      intake and body weight. Rats with CHip and VP lesions exhibited significantly
      greater weight gain and food intake compared with controls. Furthermore, CHip
      lesioned rats, but not rats with VP lesions, showed elevated metabolic activity,
      general activity in the dark phase of the light-dark cycle, and greater
      conditioned appetitive behavior, compared with control rats without these brain
      lesions. In contrast, rats with mPFC lesions were not different from controls on
      any of these measures. These results indicate that hippocampal damage interferes
      with energy and body weight regulation, perhaps by disrupting higher-order
      learning and memory processes that contribute to the control of appetitive and
      consummatory behavior.

PMID- 18831002
TI  - Evidence of multiple paternity in Morelet's Crocodile (Crocodylus moreletii) in
      Belize, CA, inferred from microsatellite markers.
AB  - Microsatellite data were generated from hatchlings collected from ten nests of
      Morelet's Crocodile (Crocodylus moreletii) from New River Lagoon and Gold Button
      Lagoon in Belize to test for evidence of multiple paternity. Nine microsatellite
      loci were genotyped for 188 individuals from the 10 nests, alongside 42
      nonhatchlings from Gold Button Lagoon. Then mitochondrial control region
      sequences were generated for the nonhatchlings and for one individual from each
      nest to test for presence of C. acutus-like haplotypes. Analyses of five of the
      nine microsatellite loci revealed evidence that progeny from five of the ten
      nests were sired by at least two males. These data suggest the presence of
      multiple paternity as a mating strategy in the true crocodiles. This information
      may be useful in the application of conservation and management techniques to the
      12 species in this genus, most of which are threatened or endangered.

PMID- 18831003
TI  - Dynamic compressive loading influences degradation behavior of PEG-PLA hydrogels.
AB  - Biodegradable hydrogels are attractive 3D environments for cell and tissue
      growth. In cartilage tissue engineering, mechanical stimulation has been shown to
      be an important regulator in promoting cartilage development. However, the impact
      of mechanical loading on the gel degradation kinetics has not been studied. In
      this study, we examined hydrolytically labile gels synthesized from poly(lactic
      acid)-b-poly(ethylene glycol)-b-poly-(lactic acid) dimethacrylate macromers,
      which have been used for cartilage tissue engineering. The gels were subject to
      physiological loading conditions in order to examine the effects of loading on
      hydrogel degradation. Initially, hydrogels were formed with two different cross
      linking densities and subject to a dynamic compressive strain of 15% at 0.3, 1,
      or 3 Hz. Degradation behavior was assessed by mass loss, equilibrium swelling and
      compressive modulus as a function of degradation time. From equilibrium swelling,
      the pseudo-first-order reaction rate constants were determined as an indication
      of degradation kinetics. The application of dynamic loading significantly
      enhanced the degradation time for the low cross-linked gels (P < 0.01) while
      frequency showed no statistical differences in degradation rates or bulk erosion
      profiles. In the higher cross-linked gels, a 3 Hz dynamic strain significantly
      increased the degradation kinetics resulting in an overall faster degradation
      time by 6 days compared to gels subject to the 0.3 and 1 Hz loads (P < 0.0001).
      The bioreactor set-up also influenced overall degradation behavior where the use
      of impermeable versus permeable platens resulted in significantly lower
      degradation rate constants for both cross-linked gels (P < 0.001). The
      compressive modulus exponentially decreased with degradation time under dynamic
      loading. Together, our findings indicate that both loading regime and the
      bioreactor setup influence degradation and should be considered when designing
      and tuning a biodegradable hydrogel where mechanical stimulation is employed.

PMID- 18831004
TI  - Altered nicotinamide adenine dinucleotide (NADH) fluorescence in dt sz mutant
      hamsters reflects differences in striatal metabolism between severe and mild
      dystonia.
AB  - The dt(sz) mutant hamster represents a unique rodent model of idiopathic
      paroxysmal dystonia. Previous data, collected post-mortem or in anesthetized
      hamsters under basal conditions, indicated the critical involvement of enhanced
      striatal neuronal activity. To assess the importance of an enhanced striatal
      neuronal activity directly during a dystonic episode, continuous monitoring of
      changes in brain metabolism and therefore neuronal activity indirectly in awake,
      freely moving animals is necessary. Determination of CNS metabolism by NADH
      measurement by laser-induced fluorescence spectroscopy in conscious dt(sz) and
      nondystonic control hamsters revealed reversible decreased NADH fluorescence
      during dystonic episodes. The degree of change corresponded to the severity of
      dystonia. This study represents the first application of this innovative method
      in freely moving animals exhibiting a movement disorder. Our data clearly confirm
      that the expression of paroxysmal dystonia in dt(sz) mutant hamsters is
      associated with enhanced striatal neuronal activity and further underscore the
      versatile application of NADH fluorescence measurements in neuroscience.

PMID- 18831005
TI  - Minocycline: a neuroprotective agent for hypoxic-ischemic brain injury in the
      neonate?
AB  - Minocycline is a second-generation tetracycline and a potential neuroprotective
      intervention following brain injury. However, despite the recognized beneficial
      effects of minocycline in a multitude of adult disease states, the clinical
      application of minocycline in neonates is contentious. Tetracyclines, as a class,
      are not usually administered to neonates, but there is compelling evidence that
      minocycline reduces brain injury after neonatal hypoxic-ischemic brain injury.
      This Review focuses on the evidence for minocycline use in neonates by
      considering aspects of pharmacology, drug regimens, functional outcomes, and
      mechanisms of action.

PMID- 18831006
TI  - Entrainment and coupling of the hamster suprachiasmatic clock by daily dark
      pulses.
AB  - The circadian rhythm of locomotor activity of hamsters kept in constant light
      (LL) can split into two distinct components that, in steady state, lie 180
      degrees apart. The splitting phenomenon is the result of antiphase circadian
      oscillations between left and right sides of the suprachiasmatic nuclei (SCN),
      the master circadian clock in mammals. In unsplit hamsters housed in LL, a single
      dark pulse produces a phase-shift of the wheel-running activity rhythm,
      accompanied by a transient down-regulation of clock gene expression in the SCN.
      In the present study, we evaluated the effects of daily 1-hr dark pulses on wheel
      running activity rhythm and on the expression of clock and nonclock proteins in
      the SCN of Syrian hamsters exposed to LL conditions. The results show that a
      daily 1-hr dark pulse entrained the rhythm of wheel-running activity of unsplit
      hamsters. In addition, in split animals, unimodal coupling of the two locomotor
      activity components was produced by daily 1-hr dark pulses. In the SCN, the
      effects of entrainment and unimodal coupling of the two separate components by
      dark observed in behavior were also evident in the bilateral expression of the
      proteins c-FOS, p-ERK, PERIOD 1, and calbindin. These results show that the
      bilaterally asymmetric SCN clock, underlying split circadian behavior, can be
      recoupled in phase and entrained by short daily dark exposure, indicating the
      synchronizing potency of darkness on the main circadian clock.

PMID- 18831007
TI  - Involvement of calpain in the process of Jurkat T cell chemotaxis.
AB  - Massive T cell infiltration into the central nervous system is a hallmark of
      multiple sclerosis (MS) and its rodent model experimental autoimmune
      encephalomyelitis (EAE), resulting in the induction of many of the
      pathophysiological events that lead to neuroinflammation and neurodegeneration.
      Thus, blocking T cell migration into the central nervous system may reduce
      disease severity in MS and EAE. One potential target for reducing T cell
      migration is inhibition of the Ca(2+)-activated neutral protease calpain.
      Previous studies in other cell types have demonstrated that migration is reduced
      by incubation of cells with calpain inhibitors. Thus, we hypothesize that calpain
      inhibition will reduce migration of T cells in response to and toward the
      chemokine CCL2. To test this hypothesis, the intracellular free Ca(2+) levels in
      Jurkat E6-1 T cells was first measured by the fura-2 assay to assess whether the
      intracellular ion environment would support calpain activation. The intracellular
      free Ca(2+) levels were found to increase in response to CCL2. The cells were
      next treated with the calpain inhibitor calpeptin in a multiwelled Boyden chamber
      with CCL2 used as the chemoattractant. These studies demonstrate that inhibition
      of calpain with its inhibitor calpeptin produces a dose-dependent inhibition of
      chemotaxis. Calpain activity, as measured by live cell imaging, was also
      increased in response to CCL2, providing further evidence of its involvement in
      the process of chemotaxis and migration. These studies provide evidence for the
      involvement of calpain in the mechanisms of chemotaxis and warrants further
      exploration in MS patient and EAE animal samples.

PMID- 18831008
TI  - Ultrastructural and temporal changes of the microvascular basement membrane and
      astrocyte interface following focal cerebral ischemia.
AB  - Microvascular integrity is lost during cerebral ischemia. Detachment of the
      microvascular basement membrane (BM) from the astrocyte, as well as degradation
      of the BM, is responsible for the loss of microvascular integrity. However, their
      ultrastructural and temporal changes during cerebral ischemia are not well known.
      Male Sprague-Dawley rats were subjected to permanent middle cerebral artery
      occlusion (MCAO) for 1, 4, 8, 12, 16, 20, and 48 hr. By using transmission
      electron microscopy, the proportion of intact BM-astrocyte contacts and electron
      densities of the BM were measured from five randomly selected microvessels in the
      ischemic basal ganglia. Their temporal changes and associations with activities
      of the matrix metalloproteinases (MMPs) were investigated. The intact portion of
      the BM-astrocyte contacts was decreased significantly within 4 hr and was rarely
      observed at 48 hr after MCAO. Decreases in the electron density and degradation
      of the BM were significant 12 hr after MCAO. The intact BM-astrocyte contacts and
      the mean BM density showed a significant positive correlation (r = 0.784, P <
      0.001). MMP-9 activity was correlated negatively with the intact BM-astrocyte
      contacts (r = -0.711, P < 0.001) and with the BM density (r = -0.538, P =
      0.0016). The increase in MMP-9 coincided temporally with the loss of the BM
      astrocyte contacts and a decrease in the BM density. Ultrastructural alterations
      occurring in the microvascular BM and its contacts with astrocyte endfeet were
      temporally associated in cerebral ischemia. Time courses of their alterations
      should be considered in the treatment targeted to the microvascular BM and its
      contact with astrocytes.

PMID- 18831009
TI  - Feasibility of immunocytochemical detection of tumor markers (XIAP,
      phosphohistone H1 and p63) in FNA cellblock samples from head and neck squamous
      cell carcinoma.
AB  - One of the major handicaps in contemporary clinical oncology is the inability to
      predict the responsiveness of any individual's malignancy to specific therapies.
      The purpose of this study was to test the feasibility of immunocytochemically
      detecting markers that may be affected by therapy or are predictive of
      therapeutic responsiveness, including phosphohistone H1 (anti-p-H1 MoAb 12D11)
      and X-linked inhibitor of apoptosis (XIAP) in small samples obtained via fine
      needle aspiration (FNA) biopsy procedure, thus improving therapeutic monitoring.
      p63, a squamous stem cell regulatory protein, was also examined. These three
      markers were studied in FNA cell block samples of head and neck squamous cell
      carcinoma (HNSCC). Twenty-eight alcohol-fixed formalin-postfixed paraffin
      embedded cell-block samples from FNAs of patients with HNSCC were subjected to
      antigen retrieval and then incubated with anti-XIAP, anti-p-H1, and anti-p63, and
      developed using EnVision-Plus reagents and diaminobenzidine as chromagen;
      Granular or heterogeneous cytoplasmic staining for XIAP and nuclear staining for
      p63 and p-H1 were considered positive. Among the 28 cases studied, the overall
      positive rates for XIAP, p-H1, and p63 were 60.7%, 96.4%, and 92.8%,
      respectively. The staining intensity for XIAP: + 70.6%, ++ 23.5%, +++ 0%, and
      ++++ 5.9%; for p-H1: + 48.1%, ++ 11.1%, +++37.0%, and ++++ 3.7%; and for p63: +
      11.5%, ++ 23.1%, +++ 53.9%, and ++++ 11.5%. The expression of p-H1 and p63
      appeared to be higher and stronger than that of XIAP in HNSCC. This study
      demonstrated the feasibility of monitoring expression of three tumor markers
      using FNA samples. p-H1 and XIAP may be useful for monitoring actions of cyclin
      dependent kinase inhibitors, XIAP-lowering, and/or apoptosis-inducing drugs,
      respectively. Future studies will focus on the impact of therapies upon these
      staining profiles.

PMID- 18831010
TI  - C1q, the recognition subcomponent of the classical pathway of complement, drives
      microglial activation.
AB  - Microglia, central nervous system (CNS) resident phagocytic cells, persistently
      police the integrity of CNS tissue and respond to any kind of damage or
      pathophysiological changes. These cells sense and rapidly respond to danger and
      inflammatory signals by changing their cell morphology; by release of cytokines,
      chemokines, or nitric oxide; and by changing their MHC expression profile. We
      have shown previously that microglial biosynthesis of the complement subcomponent
      C1q may serve as a reliable marker of microglial activation ranging from
      undetectable levels of C1q biosynthesis in resting microglia to abundant C1q
      expression in activated, nonramified microglia. In this study, we demonstrate
      that cultured microglial cells respond to extrinsic C1q with a marked
      intracellular Ca(2+) increase. A shift toward proinflammatory microglial
      activation is indicated by the release of interleukin-6, tumor necrosis factor
      alpha, and nitric oxide and the oxidative burst in rat primary microglial cells,
      an activation and differentiation process similar to the proinflammatory response
      of microglia to exposure to lipopolysaccharide. Our findings indicate 1) that
      extrinsic plasma C1q is involved in the initiation of microglial activation in
      the course of CNS diseases with blood-brain barrier impairment and 2) that C1q
      synthesized and released by activated microglia is likely to contribute in an
      autocrine/paracrine way to maintain and balance microglial activation in the
      diseased CNS tissue.

PMID- 18831011
TI  - Identifying polymer-forming SAM domains.
AB  - Sterile alpha motif (SAM) domains are common protein modules in eukaryotic cells.
      It has not been possible to assign functions to uncharacterized SAM domains
      because they have been found to participate in diverse functions ranging from
      protein-protein interactions to RNA binding. Here we computationally identify
      likely members of the subclass of SAM domains that form polymers. Sequences were
      virtually threaded onto known polymer structures and then evaluated for
      compatibility with the polymer. We find that known SAM polymers score better than
      the vast majority of known nonpolymers: 100% (7 of 7) of known polymers and only
      8% of known nonpolymers (1 of 12) score above a defined threshold value. Of 2901
      SAM family members, we find 694 that score above the threshold and are likely
      polymers, including SAM domains from the proteins Lethal Malignant Brain Tumor,
      Bicaudal-C, Liprin-beta, Adenylate Cyclase, and Atherin.

PMID- 18831012
TI  - Ultrasound-guided biopsy of the thyroid: a comparison of technique with respect
      to diagnostic accuracy.
AB  - Ultrasound-guided sampling of the thyroid represents a standard diagnostic
      procedure in the evaluation of thyroid nodules. The two techniques typically used
      are fine-needle aspiration and fine-needle capillary biopsy. Each has been used
      with success in various body sites. Recently, a comparison of these two
      techniques showed no significant difference with regard to specimen adequacy. In
      this study, the type of technique was correlated with diagnostic accuracy. For
      each technique, the preoperative cytology diagnosis was compared with the
      surgical pathology diagnosis in 46 resected thyroid nodules. No false-positive
      diagnoses were identified. No significant difference in diagnostic accuracy was
      found on comparison of the two techniques. Therefore, either technique may be
      used according to the operator's preference.

PMID- 18831013
TI  - Panorama of cytomorphological findings of filariasis in the contralateral breast,
      clinically mimicking a carcinoma in a known case: a case report.

PMID- 18831014
TI  - FNA diagnosis of Hutchison Pepper syndrome and metastatic neuroblastoma: a report
      of two cases.

PMID- 18831015
TI  - Pap smear findings in chronic renal failure patients compared with the normal
      population according to Bethesda 2001.
AB  - Dialysis remains the most common treatment for end-stage renal disease (ESRD).
      Although the increased risk of cancer after renal transplant is well documented,
      there is less certainty about the risk of cancer in patients treated only with
      dialysis. From 1997 to 2002, 262 ESRD patients received a Pap test at Baskent
      University. The smears of 149 patients who had ESRD for more than 9 months were
      compared with the smears of 150 otherwise healthy patients. All of the Pap smears
      were re-examined according to Bethesda 2001 criteria. The mean age of the
      patients was 42.88 years. Regarding micro-organisms, no statistically significant
      difference between the groups were observed. In 36 Pap smears, a shift in flora
      suggestive of bacterial vaginosis was detected. There were statistically
      significant differences between the groups. When age was considered as a marker
      of atrophy, atrophy in patients younger than 50 years was statistically different
      between the groups. Also, we determined that the shift in flora suggestive of
      bacterial vaginosis and atrophy in patients aged younger than 50 years did not
      depend on the length of hemodialysis. Of 13 patients (4.3%) who had epithelial
      cell abnormalities there were not statistically significant differences between
      the groups. In conclusion, according to our study, CRF seems not to be a
      predictive factor for cervical cancer. Shift in flora suggestive of bacterial
      vaginosis and atrophy in patients aged younger than 50 years might be the natural
      effects of uremia, and they appear not to be dependent on the length of the
      hemodialysis period.

PMID- 18831016
TI  - Is preoperative cytologic diagnosis of epithelioid sarcoma possible?
AB  - Epithelioid sarcoma (ES) is a rare malignant neoplasm of the soft tissues with a
      predilection for distal extremities of young adults. A "proximal" variant was
      recently described. The preoperative fine-needle aspiration cytology (FNAC)
      differential diagnosis with necrotizing granuloma, carcinoma, melanoma, and other
      neoplasms with epithelioid morphology can be difficult and few cases have been
      described in the literature. The authors present the preoperative FNAC findings
      of 10 aspirates of ES, corresponding to seven patients (four men and three women,
      ages 13-72 years). The cytologic features were compared with histologic features
      as well as with the FNA patterns of other neoplasms with epithelioid morphology
      that may be included in the differential diagnosis. Cytologic smears showed tumor
      cells with an epithelioid to spindle cell morphology, dispersed and in loose
      clusters in close relation with a fibrillar hyaline material. The cells showed
      moderate anisocariosis, a vast well-defined, often dense cytoplasm with
      immunoexpression of vimentin, cytokeratin, and CD 34. When the FNA cytologic
      features described above are accompanied by the adequate clinical setting and are
      supported by immunocytochemistry, an accurate preoperative cytologic diagnosis of
      ES is possible.

PMID- 18831017
TI  - Intraoperative cytologic evaluation of sentinel lymph nodes in patients with
      breast carcinoma by scrape preparation.
AB  - Intraoperative evaluation of sentinel lymph nodes (SLNs) in patients with breast
      carcinoma allows surgeons to complete axillary lymph node dissection in one
      procedure if any SLN shows metastasis. The accuracy of intraoperative
      pathological diagnosis is critical for decision-making. The purpose of this study
      was to evaluate our rapid intraoperative cytologic diagnosis of SLN through
      comparing with the final surgical pathologic diagnosis of the corresponding lymph
      nodes. A total of 454 SLNs from 159 consecutive female patients with a
      preoperative diagnosis of breast carcinoma over 3-year period were included in
      this study. After gross examination of each bisected lymph node, a scrape
      preparation was prepared for each submitted lymph node and was stained by the
      rapid Papanicolaou method. The intraoperative cytologic diagnosis was compared
      with the final surgical pathologic diagnoses. The overall sensitivity of
      intraoperative cytology was 52.5% with specificity of 100%. There were 17 false
      negative cases. Of them, six nodes had isolated tumor cells, seven nodes had
      micrometastasis (0.2-2 mm), and four nodes had macrometastasis (>2 mm). There
      were no interpretive errors identified. The size of metastasis and tumor grade
      appeared to be significant factors in detecting metastasis by cytology. In
      addition, subsequent non-SLN involvement was 9% in patients with micrometastasis
      versus 50% in patients with macrometastasis (P < 0.05). Our study shows that the
      intraoperative cytologic evaluation of SLNs in breast carcinoma is a reasonably
      accurate method. The majority of false-negative cases were due to micrometastasis
      and isolated tumor cells.

PMID- 18831018
TI  - Cytomorphological diagnosis of malignant eccrine tumors: report of two cases.
AB  - Though FNAC has been successfully used in diagnosing various neoplastic and
      nonneoplastic cutaneous lesions, there is a paucity of case reports describing
      the cytomorphological features of adnexal tumors. We hereby describe the
      cytological features of two histologically confirmed cases of malignant eccrine
      tumors. Case number 1 presented with an ulcerated infraclavicular swelling
      whereas case number 2 presented with a cystic swelling over left foot. FNA and
      histological examination of the resected specimens was performed using standard
      techniques. A cytological diagnosis of low grade papillary adenocarcinoma arising
      from skin adnexal structures was given in case number 1. Aspirate from case
      number 2 was reported as positive for malignant cells, and histological
      examination was advised. Histological examination revealed the presence of
      malignant eccrine acrospiroma in case number 1 and papillary digital
      adenocarcinoma in case number 2. Careful cytological examination displayed the
      characteristic of two cell population seen in eccrine tumors in both the cases.
      Diagnosis of malignant eccrine tumors cannot be made with certainity on cytology
      alone, hence the need to document the cytological features of these entities is
      emphasized.

PMID- 18831019
TI  - Nodular fasciitis in the submandibular gland.
AB  - Nodular fasciitis (NF) is a benign, proliferative lesion of myofibroblasts. The
      most common site of the lesion is in the upper extremities or trunk. NF in the
      head and neck is next in frequency and is the most common site in infants and
      children. In adults, NF in the submandibular region is very rare. We report a
      case of a 53-year-old man with a submandibular mass, rapidly growing for 10 days.
      Cytologic findings revealed a few sheets or clusters of small, uniform spindle
      cells. The uniform spindle cells had centrally located round to ovoid nucleus,
      but there were no nuclear atypia and atypical mitosis. There were focally loose
      stroma but we could not find chondroid or myxoid components. A partial
      parotidectomy was performed. We describe a case of NF in the submandibular
      region, adjacent to the parotid gland and review the clinical, cytologic,
      histologic, and immunohistochemical features of NF.

PMID- 18831020
TI  - Simultaneous cytological diagnosis of herpes simplex virus infection and primary
      lung cancer: report of two cases.
AB  - Herpes simplex is an uncommon cause of lower respiratory tract infection that
      requires prompt diagnosis and treatment to prevent late complications. We report
      two cases with simultaneous herpes simplex virus infection of the lower
      respiratory tract and lung carcinoma. Cytology of bronchial brushing and washing
      fluids and postbronchoscopic sputum established the diagnosis, which was further
      corroborated by real-time polymerase chain reaction.

PMID- 18831021
TI  - Synchronous high-grade squamous intraepithelial lesion and adenocarcinoma in situ
      of cervix in a young woman presenting with hyperchromatic crowded groups in the
      cervical cytology specimen: report of a case.
AB  - We report a 29-year-old woman who underwent routine gynecologic evaluation at a
      community clinic and had a cervical sample drawn for liquid-based cytologic
      evaluation. At cytology, many hyperchromatic crowded groups (HCG) were present,
      but a consensus could not be established whether the abnormal cells were
      primarily glandular or squamous with secondary endocervical glandular
      involvement. An interpretation of atypical endocervical cells, favor neoplastic,
      was rendered and biopsy advised if clinically appropriate. At biopsy, the cervix
      contained synchronous squamous cell carcinoma in situ, secondarily involving
      endocervical glands, and neighboring adenocarcinoma in situ. Immunohistochemistry
      for Ki-67 and p16(INK4A) crisply and precisely stained both the lesions, clearly
      separating them from the adjacent uninvolved mucosa. This case re-emphasizes the
      challenge associated with accurate evaluation of HCG at cytology, the
      significance of ancillary testing for surrogate markers of high-risk HPV (HR-HPV)
      infection, the need for adjunct testing for HPV-DNA in the setting of HCG at
      cervical cytology, and a recommendation to set up studies to evaluate the role of
      surrogate markers of HR-HPV infection in cytologic samples with HCG.

PMID- 18831022
TI  - Crush preparations of meningiomas: can grading be accomplished?
AB  - Crush preparations (CP) for the diagnosis of meningioma are routinely performed
      in the frozen section suite when tissue is submitted for intraoperative
      consultation. The goal of this study was to examine the cytologic features of
      meningiomas in CP and evaluate if benign meningioma (Grade 1), atypical
      meningioma (Grade 2), and malignant meningioma (Grade 3) can be diagnosed on CP.
      All cases of meningioma (1999-2007), which were submitted for frozen section at
      our institution, were retrospectively reviewed. These cases were examined
      intraoperatively by frozen section and CP. The final histologic diagnosis was
      taken as the gold standard. A total of 107 meningiomas cases were reviewed. The
      cytological features of all these cases were studied, and features such as
      pleomorphism, hemorrhage, necrosis, mitosis, and presence or absence of nucleoli
      were recorded. Using the final histopathologic diagnosis as the gold standard,
      there were 72 (Grade 1), 22 (Grade 2), and 13 (Grade 3) meningioma cases, which
      were studied. In conclusion, this study reviews the salient cytologic features of
      Grades 1-3 meningiomas. It demonstrates that it is difficult to separate Grade 1
      from Grade-2 meningioma on CP, and last, Grade-3 meningioma can be easily
      diagnosed on CP.

PMID- 18831024
TI  - Endoscopic ultrasound-guided fine needle aspiration features of a pancreatic
      neoplasm with predominantly intraductal growth and prominent tubular
      cytomorphology: intraductal tubular carcinoma of the pancreas?

PMID- 18831025
TI  - Giardiasis diagnosed on esophageal brush smears in a case of chronic alcoholic
      liver disease with esophageal candidiasis.

PMID- 18831026
TI  - Fine-needle aspiration biopsy: a historical overview.
AB  - Fine needle aspiration biopsy is a safe, inexpensive and accurate technique for
      the diagnosis of benign and malignant conditions. Its increase in popularity in
      the present days has made it a technique used on daily basis in the majority of
      medical centers in United States and around the world. However, the situation was
      not always like this. In its beginnings the procedure suffered from all kinds of
      criticism and attacks. The purpose of this manuscript is to provide an overview
      about the development of this technique from its birth to our days.

PMID- 18831027
TI  - Papillary thyroid carcinoma: evidence for intracytoplasmic formation of precursor
      substance for calcification and its release from well-preserved neoplastic cells.
AB  - Psammoma bodies (PBs) are believed to represent a process of dystrophic
      calcification over nonviable and dying tissues. Light microscopic and
      ultrastructural observations suggest that PB formation follows the intracellular
      assembly of precursor substances and their calcification leading to death of
      tumor cells and their release. It may also be the result of local secretion of
      precursor substances like collagen by tumor cells into extracellular space and
      their calcification. In an earlier reported study, we demonstrated the
      extracellular localization of various precursor forms of PBs and of irregular
      calcification in fine-needle aspiration (FNA) smears of papillary thyroid
      carcinoma (PTC). In this report, we describe a PTC case with intracellular
      formation precursor substances for calcification and their release from the well
      preserved neoplastic cells before undergoing calcification. Ultrasound-guided FNA
      smears from a small nodule in the left lobe of thyroid in a 40-year-old woman
      revealed a PTC with numerous intracytoplasmic targetoid bodies, which were
      magenta colored in MGG stain. On their release from the neoplastic cells, these
      targetoid precursor bodies were found to be forming pools of matrix material,
      some of which showed evidence of calcification. The cytologic findings were
      confirmed by histopathology of the tumor in the thyroidectomy specimen. For the
      first time, we demonstrate through cytomorpholgy the intracytoplasmic formation
      of targetoid bodies as precursor substances for calcification and their release
      from well-preserved cells in PTC. We suggest that the calcification in PTC may
      not necessarily be taking place over nonviable and dying cells.

PMID- 18831028
TI  - Cytologic features of mixed papillary carcinoma and chronic lymphocytic
      leukemia/small lymphocytic lymphoma of the thyroid gland.
AB  - We report a case of papillary thyroid carcinoma (PTC) and chronic lymphocytic
      leukemia (CLL)/small lymphocytic lymphoma of the thyroid gland. To the best of
      our knowledge, this is the first such case to be reported in the cytology
      literature. An 81-year-old male with known CLL presented for routine physical
      examination and was found to have a left-sided thyroid nodule. Thyroid ultrasound
      showed a calcified nodule. Fine-needle aspiration biopsy (FNAB) was performed and
      revealed PTC and an atypical lymphoid infiltrate that was suspicious for
      lymphoma. A partial thyroidectomy was performed and confirmed PTC with concurrent
      gland involvement by chronic lymphocytic leukemia/small lymphocytic lymphoma
      (SLL).

PMID- 18831029
TI  - Pancreatic metastasis from small cell carcinoma of the uterine cervix
      demonstrated by endoscopic ultrasonography-guided fine needle aspiration.

PMID- 18831030
TI  - Crystal structure of hypothetical protein PH0734.1 from hyperthermophilic archaea
      Pyrococcus horikoshii OT3.

PMID- 18831031
TI  - Evaluation of an inverse molecular design algorithm in a model binding site.
AB  - Computational molecular design is a useful tool in modern drug discovery. Virtual
      screening is an approach that docks and then scores individual members of
      compound libraries. In contrast to this forward approach, inverse approaches
      construct compounds from fragments, such that the computed affinity, or a
      combination of relevant properties, is optimized. We have recently developed a
      new inverse approach to drug design based on the dead-end elimination and A*
      algorithms employing a physical potential function. This approach has been
      applied to combinatorially constructed libraries of small-molecule ligands to
      design high-affinity HIV-1 protease inhibitors (Altman et al., J Am Chem Soc
      2008;130:6099-6013). Here we have evaluated the new method using the well-studied
      W191G mutant of cytochrome c peroxidase. This mutant possesses a charged binding
      pocket and has been used to evaluate other design approaches. The results show
      that overall the new inverse approach does an excellent job of separating binders
      from nonbinders. For a few individual cases, scoring inaccuracies led to false
      positives. The majority of these involve erroneous solvation energy estimation
      for charged amines, anilinium ions, and phenols, which has been observed
      previously for a variety of scoring algorithms. Interestingly, although inverse
      approaches are generally expected to identify some but not all binders in a
      library, due to limited conformational searching, these results show excellent
      coverage of the known binders while still showing strong discrimination of the
      nonbinders.

PMID- 18831032
TI  - Recurrent intrathecal methotrexate induced neurotoxicity in an adolescent with
      acute lymphoblastic leukemia: Serial clinical and radiologic findings.
AB  - Systemic and intrathecal methotrexate (MTX) are integral components of acute
      lymphoblastic leukemia (ALL) therapy, but can be associated with neurotoxicity.
      We describe here the case of an adolescent male with T-cell ALL who developed
      recurrent episodes of subacute neurotoxicity characterized by slurred speech,
      emotional lability, and hemiparesis after intrathecal MTX administration. Serial
      magnetic resonance imaging with diffusion-weighted imaging showed recurrent areas
      of restricted diffusion within cerebral hemispheric white matter, which
      correlated chronologically with the administration of intrathecal therapy and
      severity of clinical symptoms. Resolution of diffusion abnormalities did not
      preclude further toxicity and a large lesion could cause persisting symptoms.

PMID- 18831033
TI  - Levetiracetam for seizures in children with brain tumors and other cancers.
AB  - Children with brain tumors and other cancers can suffer from seizures.
      Unfortunately, most antiepileptic therapies are metabolized by the hepatic
      cytochrome P450 (CYP) system. Levetiracetam, a newer anticonvulsant, does not
      undergo CYP metabolism and does not alter the pharmacokinetics of chemotherapy,
      antiemetics, and corticosteroids, which are metabolized by the liver. We studied
      23 patients with cancer and seizures treated with levetiracetam. Over 95% of
      patients had fewer seizures, with 65.2% becoming seizure free; only one patient
      experienced an adverse reaction. Levetiracetam is effective and well tolerated in
      children with brain tumors and other cancers, who are often on multiple enzyme
      inducing drugs.

PMID- 18831034
TI  - Increased expression of the tight junction molecule claudin-18 A1 in both
      experimental colitis and ulcerative colitis.
AB  - BACKGROUND: We previously identified a major quantitative trait locus (qtl) on
      mouse chromosome 9 (Tnbs1) that confers resistance/susceptibility to
      trinitrobenzene sulfonic acid (TNBS) induced colitis. Here we wanted to identify
      possible candidate genes in this locus. METHODS: We applied micro-array
      technology and identified claudin-18 as a plausible candidate gene in the Tnbs1
      region. Subsequently we studied the expression profile of this gene by means of
      RT-PCR in resistant and susceptible mice as well as in human inflammatory bowel
      disease. RESULTS: Expression of this gene was markedly upregulated during colitis
      in mice. Also in humans relative expression of claudin-18 in patients with
      ulcerative colitis was significantly upregulated as compared to healthy
      individuals undergoing surveillance endoscopy (n = 13, P < 0.0005). Expression
      was not related to the histological severity of the disease. CONCLUSIONS:
      Claudins belong to the integral membrane proteins of the tight junction, a
      structure that seals off the intercellular space between adjacent epithelial
      cells and regulates passive diffusion of solutes and macromolecules. This study
      demonstrates for the first time that claudin-18 is expressed in human and mouse
      colon. Expression is upregulated during experimental colitis and in patients with
      ulcerative colitis. The observation that this is unrelated to the severity of
      inflammation might point to a primary defect in regulation in patients with
      ulcerative colitis and warrants further genetic examination.

PMID- 18831035
TI  - Very short peptides with stable folds: building on the interrelationship of
      Trp/Trp, Trp/cation, and Trp/backbone-amide interaction geometries.
AB  - By combining a favorable turn sequence with a turn flanking Trp/Trp interaction
      and a C-terminal H-bonding interaction between a backbone amide and an i-2 Trp
      ring, a particularly stable (DeltaG(U) > 7 kJ/mol) truncated hairpin, Ac-WI-(D
      Pro-D-Asn)-KWTG-NH(2), results. In this construct and others with a W-(4-residue
      turn)-W motif in severely truncated hairpins, the C-terminal Trp is the edge
      residue in a well-defined face-to-edge (FtE) aryl/aryl interaction. Longer
      hairpins and those with six-residue turns retain the reversed "edge-to-face"
      (EtF) Trp/Trp geometry first observed for the trpzip peptides. Mutational studies
      suggest that the W-(4-residue turn)-W interaction provides at least 3 kJ/mol of
      stabilization in excess of that due to the greater beta-propensity of Trp. The pi
      cation, and Trp/Gly-H(N) interactions have been defined. The latter can give rise
      to >3 ppm upfield shifts for the Gly-H(N) in -WX(n)G- units both in turns (n = 2)
      and at the C-termini (n = 1) of hairpins. Terminal YTG units result in somewhat
      smaller shifts (extrapolated to 2 ppm for 100% folding). In peptides with both
      the EtF and FtE W/W interaction geometries, Trp to Tyr mutations indicate that
      Trp is the preferred "face" residue in aryl/aryl pairings, presumably because of
      its greater pi basicity.

PMID- 18831036
TI  - Solution structures and DNA binding properties of the N-terminal SAP domains of
      SUMO E3 ligases from Saccharomyces cerevisiae and Oryza sativa.
AB  - SUMO E3 ligase of the Siz/PIAS family that promotes sumoylation of target
      proteins contains SAP motif in its N-terminal region. The SAP motif with a
      consensus sequence of 35 residues was first proposed to be as a new DNA binding
      motif found in diverse nuclear proteins involved in chromosomal organization. We
      have determined solution structures of the SAP domains of SUMO ligases Siz1 from
      yeast and rice by NMR spectroscopy, showing that the structure of the SAP domain
      (residues 2-105) of rice Siz1 is a four-helix bundle with an up-down-extended
      loop-down-up topology, whereas the SAP domain (residues 1-111) of yeast Siz1 is
      comprised of five helices where the fifth helix alpha5 causes a significant
      change in the alignment of the four-helix bundle characteristic to the SAP
      domains of the Siz/PIAS family. We have also demonstrated that both SAP domains
      have binding ability to an A/T-rich DNA, but that binding affinity of yeast Siz1
      SAP is at least by an order of magnitude higher than that of rice Siz1 SAP. Our
      NMR titration experiments clearly showed that yeast Siz1 SAP uses alpha2-helix
      for DNA binding more effectively than rice Siz1 SAP, which would result from the
      dislocation of this helix due to the existence of the extra helix alpha5. In
      addition, based on the structures of the SAP domains determined here and
      registered in Protein Data Bank, general features of structures of the SAP
      domains are discussed in conjunction with equivocal nature of their DNA binding.

PMID- 18831037
TI  - Crystal structure of Thermotoga maritima SPOUT superfamily RNA methyltransferase
      Tm1570 in complex with S-adenosyl-L-methionine.

PMID- 18831038
TI  - Metastatic malignant melanoma of the uterine cervix: first diagnosed on liquid
      based cytology.
AB  - Malignant melanomas of the female genital tract are uncommon lesions. The first
      case of vulvar melanomas with a subsequent malignant melanoma of the cervix
      diagnosed based on liquid-based cytology without evidence of gross pathology is
      described.

PMID- 18831039
TI  - Crystal structure of PH1733, an aspartate racemase homologue, from Pyrococcus
      horikoshii OT3.

PMID- 18831040
TI  - COCO: a simple tool to enrich the representation of conformational variability in
      NMR structures.
AB  - NMR structures are typically deposited in databases such as the PDB in the form
      of an ensemble of structures. Generally, each of the models in such an ensemble
      satisfies the experimental data and is equally valid. No unique solution can be
      calculated because the experimental NMR data is insufficient, in part because it
      reflects the conformational variability and dynamical behavior of the molecule in
      solution. Even for relatively rigid molecules, the limited number of structures
      that are typically deposited cannot completely encompass the structural diversity
      allowed by the observed NMR data, but they can be chosen to try and maximize its
      representation. We describe here the adaptation and application of techniques
      more commonly used to examine large ensembles from molecular dynamics
      simulations, to the analysis of NMR ensembles. The approach, which is based on
      principal component analysis, we call COCO ("Complementary Coordinates"). The
      COCO approach analyses the distribution of an NMR ensemble in conformational
      space, and generates a new ensemble that fills "gaps" in the distribution. The
      method is very rapid, and analysis of a 25-member ensemble and generation of a
      new 25 member ensemble typically takes 1-2 min on a conventional workstation.
      Applied to the 545 structures in the RECOORD database, we find that COCO
      generates new ensembles that are as structurally diverse-both from each other and
      from the original ensemble-as are the structures within the original ensemble.
      The COCO approach does not explicitly take into account the NMR restraint data,
      yet in tests on selected structures from the RECOORD database, the COCO ensembles
      are frequently good matches to this data, and certainly are structures that can
      be rapidly refined against the restraints to yield high-quality, novel solutions.
      COCO should therefore be a useful aid in NMR structure refinement and in other
      situations where a richer representation of conformational variability is desired
      for example in docking studies. COCO is freely accessible via the website
      www.ccpb.ac.uk/COCO.

PMID- 18831041
TI  - Structural analysis of fish versus mammalian hemoglobins: effect of the heme
      pocket environment on autooxidation and hemin loss.
AB  - The underlying stereochemical mechanisms for the dramatic differences in
      autooxidation and hemin loss rates of fish versus mammalian hemoglobins (Hb) have
      been examined by determining the crystal structures of perch, trout IV, and
      bovine Hb at high and low pH. The fish Hbs autooxidize and release hemin
      approximately 50- to 100-fold more rapidly than bovine Hb. Five specific amino
      acid replacements in the CD corner and along the E helix appear to cause the
      increased susceptibility of fish Hbs to oxidative degradation compared with
      mammalian Hbs. Ile is present at the E11 helical position in most fish Hb chains
      whereas a smaller Val residue is present in all mammalian alpha and beta chains.
      The larger IleE11 side chain sterically hinders bound O(2) and facilitates
      dissociation of the neutral superoxide radical, enhancing autooxidation. Lys(E10)
      is found in most mammalian Hb and forms favorable electrostatic and hydrogen
      bonding interactions with the heme-7-propionate. In contrast, Thr(E10) is present
      in most fish Hbs and is too short to stabilize bound heme, and causes increased
      rates of hemin dissociation. Especially high rates of hemin loss in perch Hb are
      also due to a lack of electrostatic interaction between His(CE3) and the heme-6
      propionate in alpha subunits whereas this interaction does occur in trout IV and
      bovine Hb. There is also a larger gap for solvent entry into the heme crevice
      near beta CD3 in the perch Hb (approximately 8 A) compared with trout IV Hb
      (approximately 6 A) which in turn is significantly higher than that in bovine Hb
      (approximately 4 A) at low pH. The amino acids at CD4 and E14 differ between
      bovine and the fish Hbs and have the potential to modulate oxidative degradation
      by altering the orientation of the distal histidine and the stability of the E
      helix. Generally rapid rates of lipid oxidation in fish muscle can be partly
      attributed to the fact that fish Hbs are highly susceptible to oxidative
      degradation.

PMID- 18831042
TI  - Ferric uptake regulator protein: binding free energy calculations and per-residue
      free energy decomposition.
AB  - Iron homeostasis is, in many bacterial species, mediated by the ferric uptake
      regulator (Fur). A regulatory site able to bind iron to activate Fur for DNA
      binding has been described, and a structural zinc site essential for the
      dimerization has also been proposed. They have been localized and named site 1
      and site 2, respectively, from the crystal structure of a zinc-substituted
      Pseudomonas aeruginosa Fur (PA-Fur). Notwithstanding the studies on Fur proteins
      from various species, both the precise site of iron binding and the effect on DNA
      binding affinity are still controversial. These issues were investigated here by
      molecular dynamics simulations and free energy calculations. Simulations were
      performed for eight molecular systems represented by the three forms of Fur, that
      is, apo Fur, metal-substituted Fur, and Fur complexed with DNA. Because of the
      lack of a Fur-DNA complex crystal structure, the recently published model based
      on mass spectrometry experiments on Escherichia coli Fur (EC-Fur), and the
      crystal structure of PA-Fur, was used, after adjustment to adopt a symmetric
      conformation. The simulation results suggest that the formerly proposed site 2
      is, in fact, the regulatory iron-sensing site. The calculations also predict that
      Fe(2+) at site 2 is hexacoordinated having an octahedral environment with only
      nitrogen and oxygen atoms, which is in accordance with previous spectroscopic
      characterizations. Energy decomposition pinpoints H87 as an additional amino acid
      that defines the regulatory metal site. Finally, free energy decomposition
      analysis reveals a number of amino acids potentially important in dimerization
      and in DNA binding.

PMID- 18831043
TI  - Structure of the OSR1 kinase, a hypertension drug target.

PMID- 18831044
TI  - Nonrandom distribution of intramolecular contacts in native single-domain
      proteins.
AB  - The interplay of short- and long-range interactions in protein structure and
      folding is poorly understood. This study focuses on the distribution of
      intramolecular contacts across different regions of the polypeptide chain in
      soluble single-domain proteins. We show that while the average number of
      intramolecular interactions per residue is similar across all regions of the
      sequence, the interaction counterparts are distributed nonrandomly. Two types of
      proteins are observed. The first class comprises structures that have the
      majority of their intramolecular contacts linking amino acids within the same
      region of the sequence (i.e., N-/C-terminal or intermediate portion of the
      chain). A second smaller class includes proteins that have extensive contacts
      between the N and C termini. Such extensive interactions involve primarily distal
      beta-strands and are detected via the NCR parameter, a descriptor of the number
      of contacts with interaction counterparts in specific regions of the sequence. In
      summary, the majority of single-domain proteins (first class) is dominated by
      short-range interactions between contiguous elements of secondary structure and
      has only sparse contacts among the N and C termini. This finding defies the
      common assumption that the chain termini, often spatially close in folded
      proteins, have to participate in a large number of mutual interactions. Finally,
      our results suggest that the C-terminal region of Class 2 proteins may be
      particularly effective at promoting folding upon completion of protein
      biosynthesis in the cell.

PMID- 18831045
TI  - Crystal structure of the DUF54 family protein PH1010 from hyperthermophilic
      archaea Pyrococcus horikoshii OT3.

PMID- 18831046
TI  - Computational insights into the interaction of the anthrax lethal factor with the
      N-terminal region of its substrates.
AB  - The anthrax lethal factor is a zinc metalloprotease toxin secreted by Bacillus
      anthracis which cleaves at the N-terminal region of six mitogen activated protein
      kinase kinases (MEKs) in the cell. Additionally, it is known to cleave a nine
      residue peptide "LF10," 50-fold more efficiently than nine residues of MEK1.
      There is very little sequence similarity between the MEK N-termini, thus, it is
      unclear how the lethal factor can accommodate and cleave the diverse N-termini of
      the MEKs and whether there is a hierarchy in this interaction, as there is
      between LF10 and MEK1. To investigate this problem, we carried out multiple
      molecular dynamics simulations of the lethal factor with nine residues of each of
      the substrates. Our simulations reveal that like LF10, certain MEK substrates
      have residue compositions that favor beta-sheet formation with the lethal factor
      over others. The formation of this secondary structure maintains a catalytic
      conformation. Binding energetics using the MM-PBSA method was used to rank-order
      the substrates for their affinity to LF (K(M)). On the basis of the results, we
      conclude that the LF does not equally accommodate the MEK substrates and further
      predict that there will be differences between rates of cleavage among the nine
      residue MEK N-termini.

PMID- 18831047
TI  - Insight into the antibacterial drug design and architectural mechanism of peptide
      recognition from the E. faecium peptide deformylase structure.

PMID- 18831048
TI  - Opening of the ADP-bound active site in the ABC transporter ATPase dimer:
      evidence for a constant contact, alternating sites model for the catalytic cycle.
AB  - ABC transporters are ubiquitous, ATP-dependent transmembrane pumps. The mechanism
      by which ATP hydrolysis in the nucleotide-binding domain (NBD) effects
      conformational changes in the transmembrane domain that lead to allocrite
      translocation remains largely unknown. A possible aspect of this mechanism was
      suggested by previous molecular dynamics simulations of the MJ0796 NBD dimer,
      which revealed a novel, nucleotide-dependent intrasubunit conformational change
      involving the relative rotation of the helical and catalytic subdomains. Here, we
      find that in four of five simulations of the ADP/ATP-bound dimer, the relative
      rotation of the helical and catalytic subdomains in the ADP-bound monomer results
      in opening of the ADP-bound active site, probably sufficient or close to
      sufficient to allow nucleotide exchange. We also observe that in all five
      simulations of the ADP/ATP-bound dimer, the intimate contact of the LSGGQ
      signature sequence with the ATP gamma-phosphate is weakened by the intrasubunit
      conformational change within the ADP-bound monomer. We discuss how these results
      support a constant contact model for the function of the NBD dimer in contrast to
      switch models, in which the NBDs are proposed to fully disassociate during the
      catalytic cycle.

PMID- 18831049
TI  - Mechanism for multiple-substrates recognition of alpha-aminoadipate
      aminotransferase from Thermus thermophilus.
AB  - Alpha-aminoadipate aminotransferase (AAA-AT), a homolog of mammalian kynurenine
      aminotransferase II (Kat II), transfers an amino group to 2-oxoadipate to yield
      alpha-aminoadipate in lysine biosynthesis through the alpha-aminoadipate pathway
      in Thermus thermophilus. AAA-AT catalyzes transamination against various
      substrates, including AAA, glutamate, leucine, and aromatic amino acids. To
      elucidate the structural change for recognition of various substrates, we
      determined crystal structures of AAA-AT in four forms: with pyridoxal 5'
      phosphate (PLP) (PLP complex), with PLP and leucine (PLP/Leu complex), with N
      phosphopyridoxyl-leucine (PPL) (PPL complex), and with N-phosphopyridoxyl-alpha
      aminoadipate (PPA) at 2.67, 2.26, 1.75, and 1.67 A resolution, respectively. The
      PLP complex is in an open state, whereas PLP/Leu, PPL, and PPA complexes are in
      closed states with maximal displacement (over 7 A) of the alpha2 helix and the
      beta1 strand in the small domain to cover the active site, indicating that
      conformational change is induced by substrate binding. In PPL and PLP/Leu
      complexes, several hydrophobic residues on the alpha2 helix recognize the
      hydrophobic side chain of the bound leucine moiety whereas, in the PPA complex,
      the alpha2 helix rotates to place the guanidium moiety of Arg23 on the helix at
      the appropriate position to interact with the carboxyl side chain of the AAA
      moiety. These results indicate that AAA-AT can recognize various kinds of
      substrates using the mobile alpha2 helix. The crystal structures and site
      directed mutagenesis revealed that intersubunit-electrostatic interactions
      contribute to the elevated thermostability of this enzyme.

PMID- 18831050
TI  - Coevolution in defining the functional specificity.
AB  - Covariation between sites can arise due to a common evolutionary history. At the
      same time, structure and function of proteins play significant role in
      evolvability of different sites that are not directly connected with the common
      ancestry. The nature of forces which cause residues to coevolve is still not
      thoroughly understood, it is especially not clear how coevolutionary processes
      are related to functional diversification within protein families. We analyzed
      both functional and structural factors that might cause covariation of
      specificity determinants and showed that they more often participate in
      coevolutionary relationships with each other and other sites compared with
      functional sites and those sites that are not under strong functional
      constraints. We also found that protein sites with higher number of
      coevolutionary connections with other sites have a tendency to evolve slower. Our
      results indicate that in some cases coevolutionary connections exist between
      specificity sites that are located far away in space but are under similar
      functional constraints. Such correlated changes and compensations can be realized
      through the stepwise coevolutionary processes which in turn can shed light on the
      mechanisms of functional diversification.

PMID- 18831051
TI  - The crystal structure and identification of NQM1/YGR043C, a transaldolase from
      Saccharomyces cerevisiae.

PMID- 18831052
TI  - AU-rich RNA-binding induces changes in the quaternary structure of AUH.
AB  - The human AU RNA binding protein/enoyl-Coenzyme A hydratase (AUH) is a 3-hydroxy
      3-methylglutaconyl-CoA dehydratase in the leucine degradation pathway. It also
      possesses an RNA-binding activity to AUUU repeats, which involves no known
      conserved RNA-binding domains and is seemingly unrelated to the enzymatic
      activity. In this study, we performed mass spectrometric analyses to elucidate
      the oligomeric states of AUH in the presence and absence of RNA. With a short RNA
      (AUUU) or without RNA, AUH mainly exists as a trimer in solution. On the other
      hand, the AUH trimer dimerizes upon binding to one molecule of a long RNA
      containing 24 repeats of the AUUU motif, (AUUU)(24)A. AUH was crystallized with
      the long RNA. Although the RNA was disordered in the crystalline lattice, the AUH
      structure was determined as an asymmetric dimer of trimers with a kink in the
      alignment of the trimer axes, resulting in the formation of two clefts with
      significantly different sizes.

PMID- 18831053
TI  - Consensus scoring for enriching near-native structures from protein-protein
      docking decoys.
AB  - The identification of near native protein-protein complexes among a set of decoys
      remains highly challenging. A strategy for improving the success rate of near
      native detection is to enrich near native docking decoys in a small number of top
      ranked decoys. Recently, we found that a combination of three scoring functions
      (energy, conservation, and interface propensity) can predict the location of
      binding interface regions with reasonable accuracy. Here, these three scoring
      functions are modified and combined into a consensus scoring function called
      ENDES for enriching near native docking decoys. We found that all individual
      scores result in enrichment for the majority of 28 targets in ZDOCK2.3 decoy set
      and the 22 targets in Benchmark 2.0. Among the three scores, the interface
      propensity score yields the highest enrichment in both sets of protein complexes.
      When these scores are combined into the ENDES consensus score, a significant
      increase in enrichment of near-native structures is found. For example, when 2000
      dock decoys are reduced to 200 decoys by ENDES, the fraction of near-native
      structures in docking decoys increases by a factor of about six in average. ENDES
      was implemented into a computer program that is available for download at
      http://sparks.informatics.iupui.edu.

PMID- 18831054
TI  - Brn-4 is upregulated in the deafferented hippocampus and promotes neuronal
      differentiation of neural progenitors in vitro.
AB  - Fimbria-fornix (FF), the septo-hippocampal pathway, was transected to model
      Alzheimer's disease (AD), which is characterized by loss of cholinergic afferent
      fibers in hippocampus. Various alternations may happen in the deafferented
      hippocampus. In this study, we determined the expression of Brn-4 in hippocampus
      after FF lesion. RT-PCR and Western blot showed that mRNA transcription and
      protein of Brn-4 increased significantly and reached to the peak at day 14 after
      FF lesion. Hybridization and immunohistochemistry indicated that Brn-4 signals in
      hippocampus and dentate gyrus (DG) of the deafferented side were significantly
      stronger than the normal side. More Brn-4 positive cells were identified in the
      DG of deafferented hippocampus. In the pyramidal and granular cells, Brn-4
      positive cells were all NeuN positive neurons, whereas in the neurogenic area,
      subgranular zone (SGZ), only a part of Brn-4 positive cells were NeuN positive,
      and these Brn-4/NeuN double positive neurons in SGZ and hilus of DG increased
      significantly after the trauma induced by FF lesion. In vitro Brn-4 antibody
      attenuated the role of extract from deafferented hippocampus in promoting
      differentiation of hippocampal progenitors into MAP-2 positive neurons. This
      study demonstrated that after FF lesion, Brn-4 in the deafferented hippocampus
      was upregulated and might play an important role in inducing local progenitors to
      differentiate into neurons, which may compensate for the loss of cholinergic
      afferent fibers or other dysfunctions.

PMID- 18831055
TI  - Inhibition dominates in shaping spontaneous CA3 hippocampal network activities in
      vitro.
AB  - We have assessed the balance of excitation and inhibition in in vitro rodent
      hippocampal slices exhibiting spontaneous, basal sharp waves (bSPWs). A defining
      signature of a network exhibiting bSPWs is the rise and fall in local field
      activities with frequencies ranging from 0.5 to 4.5 Hz. This variation of
      extracellular local field activities manifests at the intracellular level as
      postsynaptic potentials (PSPs). In correspondence with the local field bSPWs, we
      consider "sparse" and "synchronous" parts of bSPWs at the intracellular level. We
      have used intracellular data of bSPW-associated PSPs together with mathematical
      extraction techniques to quantify the mean and variance of synaptic conductances
      that a neuron experiences during bSPW episodes. We find that inhibitory
      conductances dominate in pyramidal cells and in a putative interneuron, and that
      inhibitory variances are much greater than excitatory ones during synchronous
      parts of bSPWs. Specifically, we find that there is at least a twofold increase
      in inhibitory conductance dominance from "sparse" to "synchronous" bSPW states
      and that this transition is associated with inhibitory fluctuations of greater
      than 10% of the change in mean inhibitory conductance. On the basis of our
      findings, we suggest that such inhibitory fluctuations during transition may be a
      physiological feature of systems expressing such population activities. In
      summary, our results provide a quantified basis for understanding the interaction
      of excitatory and inhibitory neuronal subpopulations in bSPW activities.

PMID- 18831056
TI  - Mitochondrial DNA phylogeography of Caiman crocodilus in Mesoamerica and South
      America.
AB  - The Neotropical crocodylian species, Caiman crocodilus, is widely distributed
      through Mesoamerica, northern South America, and the Amazon basin. Four
      subspecies are recognized within C. crocodilus, suggesting some geographic
      variation in morphology. In this study, we utilized mitochondrial DNA (mtDNA)
      sequence data from 45 individuals of C. crocodilus throughout its range to infer
      its evolutionary history and population structure, as well as to evaluate
      genealogical support for subspecies and their geographic distributions. Our
      molecular phylogenetic results identified five mtDNA haplotype clades with a mean
      sequence divergence of 3.4%, indicating considerable evolutionary independence
      among phylogeographic lineages. Our results were also broadly consistent with
      current subspecific taxonomy, with some important additional findings. First, we
      found substantial genetic structuring within C. c. fuscus from southern
      Mesoamerica. Second, though we confirmed the existence of a widespread Amazonian
      clade, we also discovered a cryptic and divergent mtDNA lineage that was
      indistinguishable from C. c. crocodilus based on external morphology. Third, we
      confirm the status of C. c. chiapasius as a distinct evolutionary lineage, and
      provide evidence that C. c. fuscus may be moving northward and hybridizing with
      C. c. chiapasius in northern Mesoamerica. Finally, our results parallel previous
      phylogeographic studies of other organisms that have demonstrated significant
      genetic structure over shorter geographic distances in Mesoamerica compared with
      Amazonia. We support conservation efforts for all five independent lineages
      within C. crocodilus, and highlight the subspecies C. c. chiapasius as a unit of
      particular conservation concern.

PMID- 18831057
TI  - A PCR-based marker to simply identify Saimiri sciureus and S. boliviensis
      boliviensis.
AB  - Squirrel monkeys, mainly Saimiri sciureus and S. boliviensis, are common in zoos
      and widely used in biomedical research. However, an exact species identification
      based on morphological characteristics is difficult. Hence, several molecular
      methods were proposed, but all of them are expensive and require extensive
      laboratory work. In contrast, we describe an Alu integration, which is present in
      S. boliviensis boliviensis and absent in S. sciureus. Among analyzed S. b.
      peruviensis specimens various presence/absence patterns of the integration were
      detected indicating that this study population might have originated from a
      natural hybrid zone. Based on the size of the Alu element ( approximately 300
      bp), the presence/absence pattern of the integration can easily be traced by PCR
      and followed by agarose gel electrophoresis.

PMID- 18831058
TI  - Short-term low-salinity tolerance by the longhorn sculpin, Myoxocephalus
      octodecimspinosus.
AB  - The bottom-dwelling, longhorn sculpin, Myoxocephalus octodecimspinosus, is
      traditionally viewed as a stenohaline marine fish, but fishermen have described
      finding this sculpin in estuaries during high tide. Little is known about the
      salinity tolerance of the longhorn sculpin; thus, the purposes of these
      experiments were to explore the effects of low environmental salinity on ion
      transporter expression and distribution in the longhorn sculpin gill. Longhorn
      sculpin were acclimated to either 100% seawater (SW, sham), 20% SW, or 10% SW for
      24 or 72 hr. Plasma osmolality, sodium, potassium, and chloride concentrations
      were not different between the 20 and 100% treatments; however, they were 20-25%
      lower with exposure to 10% SW at 24 and 72 hr. In the teleost gill, regulation of
      Na(+), K(+)-ATPase (NKA), Na(+)-K(+)-2Cl(-) cotransporter (NKCC1), and the
      chloride channel, cystic fibrosis transmembrane conductance regulator (CFTR) are
      necessary for ion homeostasis. We immunolocalized these proteins to the
      mitochondrion-rich cell of the gill and determined that acclimation to low
      salinity does not affect their localization. Also, there was not a downregulation
      of gill NKA, NKCC1, and CFTR mRNA or protein during acclimation to low
      salinities. Collectively, these results suggest that down to 20% SW longhorn
      sculpin are capable of completely regulating ion levels over a 72-hr period,
      whereas 10% SW exposure results in a significant loss of ions and no change in
      ion transporter density or localization in the gill. We conclude that longhorn
      sculpin can tolerate low-salinity environments for days but, because they cannot
      regulate ion transporter density, they are unable to tolerate low salinity for
      longer periods or enter freshwater (FW). The genus Myoxocephalus has three FW
      species, making this group an excellent model to test evolutionary and
      physiological mechanisms that allow teleosts to invade new low salinities
      successfully.

PMID- 18831059
TI  - Monoamine oxidase-B activity is not involved in the neuroinflammatory response
      elicited by a focal freeze brain injury.
AB  - Cryolesion of the frontoparietal cortex in mice is a well-described brain injury
      paradigm that results in increased astrogliosis surrounding the lesion site and
      is accompanied by a prominent increase in the MAO-B levels in astrocytes. Whether
      these increased MAO-B levels contribute to cellular damage or modulate reactive
      astrocytosis remains unclear. MAO-B activity may contribute to cellular damage,
      since its metabolism products are highly toxic to the cells. Additionally, it has
      been suggested that MAO-B inhibition may regulate astrocytic reaction. In this
      study, we have determined the relative contribution of MAO-B activity to the
      outcome following freeze injury. Freeze injury induced a prominent increase of
      several inflammatory markers, including ICAM, Mac-1, EB22, and GFAP. Inhibition
      of MAO-B activity using the selective inhibitor PF9601N did not reduce this
      cryolesion-induced inflammatory response. Additional data revealed that the
      expression of several cryolesion-induced cell death genes, such as Fas, Rip, p53,
      and ICE, was not reduced in PF9601N-treated mice, evidencing that MAO-B activity
      did not contribute to cryolesion-induced cell death. Definitive functional
      analysis of the mice using the ladder beam task revealed that MAO-B inhibition
      did not improve the cryolesion-induced motor impairment. These data strongly
      suggest that, although MAO-B is highly expressed in the area surrounding the
      lesion site, its activity does not contribute to the cellular damage or play any
      role in regulating astrocytic reactivity.

PMID- 18831060
TI  - Robinow syndrome: phenotypic variability in a family with a novel intragenic ROR2
      mutation.
AB  - Robinow syndrome comprises dysmorphic facial features, short stature,
      brachymesomelia, segmental spine defects, and genital hypoplasia. The range of
      severity in this disorder is broad. We report on the clinical and molecular
      findings of two sib pairs from the same extended family with Robinow syndrome due
      to a novel intragenic ROR2 deletion involving exons 6 and 7 that could not be
      detected by sequencing. The affected individuals exhibited variability with
      respect to the cleft lip, cleft palate, and cardiac findings and for the presence
      in one of the patients of syringomyelia, which has not been previously reported
      in Robinow syndrome.

PMID- 18831061
TI  - Kapur-Toriello syndrome: further delineation.
AB  - We report on a Mexican patient with mental retardation, cleft lip and palate, and
      facial anomalies characteristic of Kapur-Toriello syndrome described in 1991 by
      Kapur and Toriello in two sibs. The condition was considered a previously
      undescribed autosomal recessive disorder and only one patient has been reported
      since that time. The clinical manifestations observed in our patient confirm some
      characteristics as part of the entity. In view of rarity, it is necessary to
      describe additional cases.

PMID- 18831062
TI  - Genotype-phenotype relationship for localization and age distribution of
      telangiectases in hereditary hemorrhagic telangiectasia.
AB  - Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disease
      characterized by arteriovenous malformations (AVMs) ranging from telangiectases
      to larger AVMs. Mutations in two genes cause HHT; ENG (HHT1) and ACVRL1 (HHT2).
      Although the hallmark for clinical diagnosis is the presence of telangiectases,
      there are few publications reporting the relative distribution and frequency of
      these features between HHT1 and HHT2. Here, the results of such analysis of
      telangiectases in 268 patients with HHT1 and 130 patients with HHT2 are
      described. Localization of the telangiectases is reported, and patients were
      clustered by age to estimate the site prevalence for different age categories. We
      show that telangiectases of the nasal mucosa are present at a higher prevalence
      and start to appear earlier in life than those of the oral mucosa or dermal sites
      in patients with either HHT1 or HHT2. Oral and nasal mucosal telangiectases are
      present earlier in life in patients with HHT1 compared to patients with HHT2,
      whereas dermal lesions are more frequent and appear earlier in life in patients
      with HHT2. In patients with either HHT1 or HHT2, the number of sites affected
      increases with age. In patients with HHT1, more women than men had skin
      telangiectases, particularly on the face. These results confirm that the
      frequency of AVMs differ between patients with HHT1 and HHT2, and that these
      differences can be detected on physical examination.

PMID- 18831063
TI  - All in the family: disclosure of "unwanted" information to an adolescent to
      benefit a relative.
AB  - Ethical assessments of clinical decisions are typically based on the preferences
      and interests of the individual patient. However, some clinical interventions,
      such as genetic testing or organ donation, may involve multiple family members.
      In these cases, one family member may have the potential to benefit, while
      another family member is exposed to potential physical or psychological risk. In
      the research setting, the balancing of benefits and risks between family members
      may be further complicated by uncertainty about their magnitude and likelihood.
      In addition, when the individual facing these apparently uncompensated risks is a
      child, the situation becomes particularly ethically complicated, as we
      appreciated in a recent case. Investigators at the National Cancer Institute were
      faced with a decision about whether it would be appropriate to disclose
      apparently "unwanted" research test results (length of telomeres in leukocyte
      subsets) to an adolescent about risk of future disease (dyskeratosis congenita),
      possibly causing psychological harm and an ethical wrong. These issues were not
      expected at the outset of the family's study participation but rather emerged
      with new data about the research tests. Disclosure of the research finding was an
      important consideration in order to avoid using the adolescent as a stem-cell
      donor for his sister. Disclosure to the adolescent could not be justified by
      merely considering the immediate interests and preferences of the adolescent.
      However, an expanded ethical analysis that considers the adolescent's familial
      context offers a more complete picture of the adolescent's interests and
      preferences which provides justification for disclosure.

PMID- 18831064
TI  - Familial recurrence of SOX2 anophthalmia syndrome: phenotypically normal mother
      with two affected daughters.
AB  - The SOX2 anophthalmia syndrome is emerging as a clinically recognizable disorder
      that has been identified in 10-15% of individuals with bilateral anophthalmia.
      Extra-ocular anomalies are common. The majority of SOX2 mutations identified
      appear to arise de novo in probands ascertained through the presence of
      anophthalmia or microphthalmia. In this report, we describe two sisters with
      bilateral anophthalmia/microphthalmia, brain anomalies and a novel heterozygous
      SOX2 gene single-base pair nucleotide deletion, c.551delC, which predicts
      p.Pro184ArgfsX19. The hypothetical protein product is predicted to lead to
      haploinsufficient SOX2 function. Mosaicism for this mutation in the SOX2 gene was
      also identified in their clinically unaffected mother in peripheral blood DNA.
      Thus it cannot be assumed that all SOX2 mutations in individuals with
      anophthalmia/microphthalmia are de novo. Testing of parents is indicated when a
      SOX2 mutation is identified in a proband.

PMID- 18831065
TI  - Intracellular glutathione mediates the denitrosylation of protein nitrosothiols
      in the rat spinal cord.
AB  - Protein S-nitrosothiols (PrSNOs) have been implicated in the pathophysiology of
      neuroinflammatory and neurodegenerative disorders. Although the metabolically
      instability of PrSNOs is well known, there is little understanding of the factors
      involved in the cleavage of S-NO linkage in intact cells. To address this issue,
      we conducted chase experiments in spinal cord slices incubated with S
      nitrosoglutathione (GSNO). The results show that removal of GSNO leads to a rapid
      disappearance of PrSNOs (t(1/2) approximately 2 hr), which is greatly accelerated
      when glutathione (GSH) levels are raised with the permeable analogue GSH ethyl
      ester. Moreover, PrSNOs are stable in the presence of the GSH depletor diethyl
      maleate, indicating that GSH is critical for protein denitrosylation. Inhibition
      of GSH-dependent enzymes (glutathione S-transferase, glutathione peroxidase, and
      glutaredoxin) and enzymes that could mediate denitrosylation (alcohol
      dehydrogense-III, thioredoxin and protein disulfide isomerase) do not alter the
      rate of PrSNO decomposition. These findings and the lack of protein
      glutathionylation during the chase indicate that most proteins are denitrosylated
      via rapid transnitrosylation with GSH. The differences in the denitrosylation
      rate of individual proteins suggest the existence of additional structural
      factors in this process. This study is relevant to our recent discovery that
      PrSNOs accumulate in the central nervous system of patients with multiple
      sclerosis.

PMID- 18831066
TI  - Bradykinin selectively modulates the blood-tumor barrier via calcium-induced
      calcium release.
AB  - To investigate the underlying mechanism for the selective modulation of
      permeability of the blood-tumor barrier by small dose of BK, we established cell
      lines of rat brain microvascular endothelial cells (BMECs) and astrocytes by
      primary culture from neonatal rats. BMECs, astrocytes, or C6 glioma cells were
      treated with BK, and changes of intracellular NO and intracellular calcium level
      were measured with a fluorescent spectrophotometer. Similarly to the observations
      in astrocytes, although the initial application of BK easily triggered a
      ryanodine-mediated calcium-induced calcium release (CICR), we also detected a
      long-lasting intracellular nitric oxide (NO) elevation in C6 glioma cells upon BK
      treatment. However, BMECs are not the direct target of BK. Further study showed
      that ryanodine-mediated CICR contributes greatly to the secondary NO elevation
      induced by BK treatment. With an in vitro blood-tumor barrier (BTB) model, we
      demonstrated that NO generated in C6 glioma cells might act as an intercellular
      messenger and play an important role in the selective modulation of permeability
      of BMECs by BK. In conclusion, BK triggered CICR in C6 glioma cells, and the
      associated NO generation might be the underlying mechanism for the selective
      modulation of BTB permeability by BK.

PMID- 18831067
TI  - Regulation of relaxin 3 gene expression via cAMP-PKA in a neuroblastoma cell
      line.
AB  - Relaxin 3 is expressed in neurons of the brain stem that inneravate wide areas of
      the forebrain. Relaxin 3 mRNA levels in these neurons are increased in response
      to restraint stress, and by central administration of corticotropin-releasing
      factor (CRF). In the present study, we observed that relaxin 3 was expressed in a
      mouse neuroblastoma cell line, Neuro2a, and investigated the intracellular
      signaling that activated relaxin 3 gene transcription in vitro. By means of a
      clone stably transfected with a relaxin 3 promoter-EGFP gene, we observed that
      dibutyryl cyclic AMP and forskolin increased the relaxin 3 promoter activity.
      These increases were inhibited by pretreatment with PKA inhibitors, H89 and
      KT5720. Moreover, the promoter activity was enhanced by CRF treatment after
      expression of CRF-R1 receptor on the cells. Taken together, these results
      indicate that relaxin 3 transcription is activated via the cAMP-PKA pathway in
      the downstream of CRF-R1.

PMID- 18831068
TI  - DNA breakage and induction of DNA damage response proteins precede the appearance
      of visible mutant huntingtin aggregates.
AB  - Huntington's disease (HD) is a neurodegenerative disorder that follows an
      autosomal-dominant inheritance pattern. The pathogenesis of the disease depends
      on the degree of expansion of triplet (CAG) repeats located in the first exon on
      the gene. An expanded polyglutamine tract within the protein huntingtin (Htt)
      enables a gain-of-function phenotype that is often exhibited by a dysfunctional
      oligomerization process and the formation of protein aggregates. How this process
      leads to neurodegeneration remains undefined. We report that expression of a Htt
      fragment containing an expanded glutamine tract induces DNA damage and activates
      the DNA damage response pathway. Both single-strand and double-strand breaks are
      observed as the mutant protein accumulates in the cell; these breaks precede the
      appearance of detectable protein aggregates containing mutant Htt. We also
      observe activation of H2AX, ATM, and p53 in cells expressing mutant Htt, a
      predictable response in cells containing chromosomal breakage. Expression of wild
      type Htt does not affect the integrity of DNA, nor does it activate the same
      pathway. Furthermore, DNA damage and activated H2AX are present in HD transgenic
      mice before the formation of mutant Htt aggregates and HD pathogenesis. Taken
      together, our data suggest that the expression of mutant Htt causes an
      accumulation of DNA breaks that activates the DNA damage response pathway, a
      process that can disable cell function. Because these events can lead to
      apoptosis, it is possible that the DNA damage response pathway activated by
      single- and double-strand breaks that we found contributes to neurodegeneration.

PMID- 18831069
TI  - Deletion of the amino-terminal domain of the prion protein does not impair prion
      protein-dependent neuronal differentiation and neuritogenesis.
AB  - The cellular prion protein (PrP(C)) is a highly conserved glycoprotein of unknown
      biological function. To gain insight into the physiological role of PrP(C), we
      generated a novel PrP knockout cell line, named PrP(o/o) ML, by immortalization
      of neuroepithelial precursor cells derived from the cerebellum of PrP-knockout
      mice using the temperature-sensitive simian virus 40 (SV40) large T antigen. We
      demonstrated that the PrP(o/o) ML cell line is a unipotent precursor line with
      glutamatergic properties, which can acquire neuronal features when cultivated
      under specific conditions. The role of the prion protein in the process of
      neuronal differentiation was then analyzed in the PrP(o/o) ML cells reconstituted
      with either the full-length or an amino-terminally deleted form of the prion
      protein. We show that the expression of PrP(C) facilitates the processes of
      neuronal differentiation and neuritogenesis and that the deletion of its amino
      terminal domain reduces the efficiency, but does not suppress this activity. This
      cell line represents a useful tool for studying PrP-dependent signal transduction
      pathways during differentiation of neuronal stem/precursor cells.

PMID- 18831071
TI  - Profile of depression in adolescents with inflammatory bowel disease:
      implications for treatment.
AB  - BACKGROUND: The purpose was to determine the utility of including neurovegetative
      symptoms in assessments of depression in youth with inflammatory bowel disease
      (IBD). METHODS: Forty-one youth with IBD and concurrent depressive symptomatology
      were enrolled in an intervention trial and received either 9 modules of cognitive
      behavioral therapy (PASCET-PI) or treatment as usual (TAU). Youth and their
      primary caregivers completed the Children's Depression Inventory (CDI) at pre-
      (T1) and posttreatment (T2). Disease severity measures and current steroid dosage
      were obtained at each timepoint. Change in the individual items of the CDI was
      compared across groups and examined in association with change in physical
      illness course. RESULTS: Paired sample t-tests revealed significant changes in
      CDI item scores from T1 to T2 for a majority of the depressive symptoms assessed
      in the PASCET-PI group, but not for the TAU group. These changes did not appear
      to be linked to changes in disease severity and/or steroid dosage across these
      same timepoints. CONCLUSIONS: The inclusion of somatic items in the assessment of
      depression in physically ill youth is important, as these symptoms seem to
      respond to psychotherapeutic intervention. The present results would suggest that
      improvements in depressive symptomatology are not solely related to improvements
      in the course of IBD and that these items do reflect an important part of the
      profile of depressive symptoms in youth with IBD. Future research is warranted to
      replicate present findings and explore the generalizability of these results to
      other pediatric illness populations.

PMID- 18831070
TI  - Controlled contusion injury alters molecular systems associated with cognitive
      performance.
AB  - We investigated whether a learning impairment after a controlled cortical impact
      (CCI) injury was associated with alterations in molecules involved in synaptic
      plasticity and learning and memory. Adult male rats with moderate CCI to the left
      parietal cortex, tested in a Morris water maze (MWM) beginning at postinjury day
      10, showed impaired cognitive performance compared with sham-treated rats. Tissue
      was extracted for mRNA analysis on postinjury day 21. The expression of brain
      derived neurotrophic factor (BDNF), synapsin I, cyclic-AMP response element
      binding protein (CREB), and calcium-calmodulin-dependent protein kinase II (alpha
      CAMKII) were all significantly decreased compared with sham injury levels within
      the ipsilateral hippocampus after CCI. No significant molecular level changes
      were found in the contralateral hippocampus. Decreased expression of BDNF and
      synapsin I was also found within the ipsilateral parietal cortex of CCI-injured
      rats compared with shams. However, BDNF and synapsin I expressions were
      significantly increased in the contralateral parietal cortex of the CCI rats.
      CREB expression was significantly decreased within the contralateral cortex of
      the CCI group. These findings show enduring reductions in the expression of BDNF,
      synapsin I, CREB, and alpha-CAMKII ipsilateral to a CCI injury, which seem
      associated with the spatial learning deficits observed in this injury model. In
      addition, the delayed increase in the expression of BDNF and synapsin I within
      the cortex contralateral to CCI may reflect restorative processes in areas
      homotypical to the injury.

PMID- 18831072
TI  - Overexpression of CD49f in precursor B-cell acute lymphoblastic leukemia:
      potential usefulness in minimal residual disease detection.
AB  - BACKGROUND: The persistence of minimal residual disease (MRD) following therapy
      is an established prognostic factor in precursor B-cell acute lymphoblastic
      leukemia (pB-ALL). Detection of MRD in pB-ALL by flow cytometric
      immunophenotyping requires demonstration of abnormal antigen expression in
      leukemic B-cell precursors relative to that of normal B-cell precursors. The gene
      encoding CD49f (integrin alpha-6) is one of several whose overexpression in pB
      ALL at diagnosis has been associated with the subsequent detection of MRD.
      However, whether CD49f might be a useful reagent in the immunophenotypic
      detection of MRD in pB-ALL has not been evaluated. METHODS: We evaluated CD49f
      expression by 4-color flow cytometry in normal B-cell precursors, and in a series
      of cases of pB-ALL, both at diagnosis and at intervals following the initiation
      of therapy. RESULTS: In 10 control marrow samples, CD49f was undetectable or
      extremely dim in all but a minor subset of normal CD19+ B-lineage cells, whereas
      in 11 of 15 cases (73%) of pB-ALL, CD49f was moderate or bright at diagnosis, and
      persisted or became brighter after initiation of therapy. MRD detected using
      CD49f corresponded precisely with that obtained using a standard panel of
      antibodies, and permitted the detection of leukemic populations comprising as
      little as 0.02% of cells. Of the four pB-ALL cases in which CD49f was
      undetectable or dim at diagnosis, MRD was detected in two; in one of these, CD49f
      expression was substantially increased in the leukemic cells that persisted
      following initiation of therapy. CONCLUSIONS: CD49f is commonly overexpressed in
      p-B-ALL, and represents a potentially useful marker for the immunophenotypic
      detection of MRD.

PMID- 18831073
TI  - Intrauterine growth in multiple pregnancies in relation to fetal number,
      chorionicity and gestational age.
AB  - OBJECTIVES: To examine birth weight in dichorionic and monochorionic twins and
      trichorionic triplets, and to estimate the relative independent importance on
      growth of fetal number, chorionicity and gestational age. METHODS: Four groups of
      pregnancies were examined: 12,816 singleton pregnancies, 302 monochorionic twin
      pregnancies, 569 dichorionic twin pregnancies, and 97 trichorionic triplet
      pregnancies. Chorionicity was determined at 10-14 weeks on the basis of the
      presence or absence of the lambda sign in twins, and by examining the ipsilon
      zone in triplets. The relationship between birth weight and gestational age in
      singletons was established, and using this equation the expected mean birth
      weights for all gestational ages were calculated. For each case in all groups,
      the difference between the observed birth weight for each fetus and the
      appropriate normal mean for gestation in singletons was calculated (Z-score).
      Multiple regression analysis was used to examine the independent contribution of
      gestational age, number of fetuses and chorionicity in the prediction of actual
      birth weight and birth weight Z-score. RESULTS: Birth weight Z-score was
      significantly lower than the expected mean in singletons for dichorionic twins,
      monochorionic twins and trichorionic triplets (t = 15.4, P < 0.0001, t = 21.7, P
      < 0.0001 and t = 19.9, P < 0.0001, respectively). Furthermore, the reduction in
      expected birth weight was significantly greater for monochorionic twins and
      trichorionic triplets compared with dichorionic twins (t = 6.3, P < 0.0001 and t
      = 7.8, P < 0.0001, respectively). Multiple regression analysis demonstrated that
      number of fetuses, presence of a monochorionic placenta and gestational age were
      independently associated with birth weight Z-score, the strongest effect being
      fetal number, followed by monochorionicity (t = - 23.4, P < 0.0001, t = - 8.3, P
      < 0.0001 and t = - 4.9, P < 0.0001, respectively). CONCLUSIONS: The finding that
      monochorionic twins were of lower adjusted birth weight than dichorionic twins,
      and the significant independent effect of chorionicity on birth weight suggest
      that monochorionic placentation in itself has an effect on intrauterine growth.
      The effect of fetal number independent of chorionicity is demonstrated by the
      lower birth weight of trichorionic triplets compared with dichorionic twins.

PMID- 18831074
TI  - Methadone wellness. Doctor and advocate Sarz Maxwell on the science--and madness.
      Interview by Enid Vazquez.

PMID- 18831075
TI  - Wellness checklist. Important things to consider when you're HIV-positive.

PMID- 18831076
TI  - Nightsweats and T-cells. Where business and social service meet.

PMID- 18831077
TI  - Long-term survivors of HIV and wellness. No longer an oxymoron.

PMID- 18831078
TI  - Spotlight on Houston Buyers Club. Club founder Fred Walters, Jr. talks about the
      history of HBC and the importance of nutritional supplements.  Interview by Jeff
      Berry.

PMID- 18831080
TI  - Abstracts from the First Meeting of Argentine Biology Societies, August 2007,
      Cordoba, Argentina.

PMID- 18831079
TI  - Comparing two integrase inhibitors. The first head-to-head study comparing
      raltegravir and elvitegravir.

PMID- 18831081
TI  - Accessibility and acceptability of public sexual health clinics for adult clients
      in New South Wales, Australia.

PMID- 18831082
TI  - HIV prevention during a sexual health consultation; a suggested quality audit.

PMID- 18831083
TI  - A drink's purple reign.

PMID- 18831084
TI  - Time 100 scientists & thinkers. Michael Bloomberg.

PMID- 18831085
TI  - [Narratives of prostitution in Counter-Reformation Rome].

PMID- 18831086
TI  - [Esophageal neoplasm and stomach neoplasm].

PMID- 18831087
TI  - Love and marriage in the Spanish empire: depictions of holy matrimony and gender
      discourses in the seventeenth century.

PMID- 18831088
TI  - [Reinitiation of database registration of patients of esophageal neoplasm in
      Japan].

PMID- 18831089
TI  - [Advancement in surgical techniques for esophageal neoplasm under thoracoscopy].

PMID- 18831090
TI  - [Preventive effect of the oral carbonaceous absorbent for progression of chronic
      kidney failure: report of a RCT].

PMID- 18831091
TI  - [Proposal for revision of guideline for treatment of stomach cancer].

PMID- 18831092
TI  - [Current topics of adjunct therapy for stomach cancer after surgery].

PMID- 18831093
TI  - [Stethoscopy of the heart].

PMID- 18831094
TI  - Abstracts from the 6th Annual World Congress on the Insulin Resistance Syndrome,
      25-27 September 2008, Los Angeles, California, USA.

PMID- 18831095
TI  - A health plan work in progress: hospital-physician price and quality
      transparency.
AB  - Responding to large employers' interest in greater health care price and quality
      transparency, health plans are developing consumer tools to compare price and
      quality information across hospitals and physicians, but the tools' pervasiveness
      and usefulness are limited, according to findings from the Center for Studying
      Health System Change's (HSC) 2007 site visits to 12 nationally representative
      metropolitan communities. Many large employers view price and quality
      transparency as key to a broader consumerism strategy, where employees take more
      responsibility for medical costs, lifestyle choices and treatment decisions. Some
      health plans believe providing price and quality information to enrollees is a
      competitive advantage, while others are skeptical about the benefits and are
      proceeding cautiously to avoid potential unintended consequences. Health plans
      are in various stages of making price information available to enrollees. Plans
      generally provide some type of price information on inpatient and outpatient
      procedures and services from data based on their own negotiated prices or through
      aggregated health plan claims data obtained through a vendor; few plans provide
      price information on services in physician offices. However, the information
      provided often lacks specificity about individual providers, and its availability
      is often limited to enrollees in specific geographic areas. Health plans
      generally rely on third-party sources to package publicly available quality
      information instead of using information gleaned from their own claims or other
      data. Health plans' ability to advance price and quality comparison tools to the
      point where a critical mass of consumers trust and use the information to choose
      physicians and hospitals will likely have considerable influence on the ultimate
      success of broader health consumerism efforts.

PMID- 18831096
TI  - Dear (food) diary. A new study shows that dieters can double their weight loss by
      jotting down what foods they eat.

PMID- 18831097
TI  - Rash redux. Why chicken pox strikes some adults a second time--as shingles--and
      how to avoid the repeat.

PMID- 18831098
TI  - The drinking age. A lower age would be safe.

PMID- 18831099
TI  - The drinking age. The status quo has bombed.

PMID- 18831100
TI  - Food safety's dirty little secret. Increasingly, the government is leaving the
      job in private hands.

PMID- 18831102
TI  - Coping with sexual woes.

PMID- 18831101
TI  - Sex, health and happiness. Love lives keep getting longer and better. Yours can
      too.

PMID- 18831103
TI  - A little aphrodisiac science. These foods may conjure up thoughts of sex, but do
      they deliver?

PMID- 18831104
TI  - The difference sex therapy can make.

PMID- 18831105
TI  - Let's teach our children well.

PMID- 18831106
TI  - Here comes the controversial new sugar substitute stevia. Soon it could sweeten
      foods from yogurt to diet soda.

PMID- 18831107
TI  - Determinants of divorce in nineteenth-century Flanders.
AB  - In 1830, the year Belgium became independent, there were four divorces in
      Belgium. From about 1870 to 1910, there were about one hundred divorces per year,
      and since 1910, there have been about 1,000. The aim of this research is to
      investigate the factors that played a role in the increase in the number of
      divorces in Belgium in the course of the nineteenth century. The research relates
      to information from four Flemish municipalities for the period 1800-1913. Results
      indicate that an explanation of the rising divorce rate can be sought in the
      psychological and social consequences of the more pronounced shift in marriage,
      gender and family expectations. Increasing numbers of women threw themselves more
      and more into their gender-specific expressive gender role, whereas the objective
      opportunities and attainability of this role did not increase commensurately. The
      result was role strain: high marriage and family expectations soon come up
      against intrinsic limitations. As a result of this, both individual and general
      frustration increased, and this was an ideal social substratum for facilitating
      divorce.

PMID- 18831108
TI  - The market in concubines in Jiangnan during Ming-Qing China.
AB  - The traffic in concubines flourished in Ming-Qing Jiangnan as a result of large
      scale interactions of political and socioeconomic contexts. How women were
      situated within the system is central to this study, which revolves around two
      major arguments. First, the traffic in concubines as a means for disaster relief
      during difficult times was legitimized as a benevolent policy. Second, women were
      not necessarily the victims of the commercialized market in concubines. To study
      concubinage in general and individual concubines in the market system in
      Jiangnan, the following issues command attention: the political and socioeconomic
      conditions fostering concubinage, the market system of women, the roles of
      brokers, the value indicators and resultant prices, the transaction procedures
      for the sale of women with specific contents of contracts, the effects of the
      market system on the concubines' lives, and the regulations of law and the
      judicial practice in penal cases.

PMID- 18831109
TI  - Anachronisms or failures? Family strategies in the sixteenth century, as drawn
      from collective biographies of solicitors in Aix-en-Provence.
AB  - This article highlights the patterns that can be observed in the matrimonial
      alliances of solicitors in sixteenth-century Aix-en-Provence and family
      strategies understood as a corpus of rational decisions bearing on the long term.
      Defined this way, family strategies applied to sixteenth-century solicitors are
      an anachronism. The new and unstable context in which the sixteenth-century
      solicitor found himself prevented families from having a clear view of the
      objectives to achieve and from devising a rational strategy. The article presents
      the model that most of the solicitors' alliances followed and suggests the
      obstacles that appeared before the main actor in family planning, the one who
      wielded paternal authority, in the creation of these alliances. The example of
      the Maria family shows women who decided, against the will of their family, whom
      they would marry. This article highlights the historian's reconstruction of
      typical family behavior and the limited possibilities that families had to plan
      over the long term.

PMID- 18831110
TI  - Sara Ruddick's theory of maternal thinking applied to traditional Irish
      mothering.
AB  - This paper uses Sara Ruddick's theory of maternal thinking to explain patterns of
      Irish mothering that developed in Ireland following the Great Famine of 1845
      1852. Ruddick's central thesis, that maternal thinking develops strategies for
      preserving the life of the child, fostering the child's growth, and shaping an
      acceptable child, is applied to the intersecting influences of famine memory,
      religion, education, and emigration in post-famine Ireland. The strict,
      moralistic, and highly inhibiting features of Irish culture that dominated the
      nineteenth and twentieth centuries are traceable to patterns of mothering that
      developed after the famine. While Irish mothers are often blamed for instilling
      values that stressed sexual repression and guilt, other cultural factors
      influenced maternal thinking. Mothers did foster highly repressive moral values
      that encouraged permanent celibacy and delayed marriage. This paper examines the
      larger cultural features that derived from political oppression and the famine as
      they imprinted these values.

PMID- 18831111
TI  - Boundaries and opportunities: comparing slave family formation in the antebellum
      South.
AB  - Our understanding of the marriage strategies and family formation of enslaved
      people remains clouded by disagreement among contemporary scholars. A perusal of
      the historical literature suggests that two issues lay at the root of this
      disagreement: First, scholars disagree over the extent to which slave family life
      was shaped by the external factors of slavery, or rather slave agency; and
      second, scholars appear reluctant to abandon their singular views of the slave
      family. This article addresses both of these gaps by formulating a middle ground
      in the slave agency debate and by redefining the slave family in plural form. An
      analysis of the boundaries and opportunities for family formation in northern
      Virginia and lowcountry South Carolina, this study shows that while the
      establishment of co-residential two-parent households was the ideal for slaves,
      not all were able to realize that ideal, and those that could not adapted their
      marriage strategies and family lives accordingly.

PMID- 18831112
TI  - Different historical trajectories and family diversity among Chinese, Japanese,
      and Koreans in the United States.
AB  - Chinese, Japanese, and Korean American families in the United States share
      several similarities, but they should not be interpreted as the sameness. Each
      group has gone through different immigration trajectories, and family members in
      a group have had different experiences. To get further knowledge of different
      family experiences in contemporary U.S. society, the trajectories of the family
      relationships among different Asian ethnic groups are examined. We specifically
      look at the time from arrival to World War II, from World War II to the 1960s,
      and after the 1960s.

PMID- 18831113
TI  - Restructuring municipal government: labor-management relations and worker mental
      health.
AB  - This study is a mixed-method investigation of the association between labor
      management relations and employees' mental health in a municipal sector
      undergoing New Public Management-style restructuring. Analysis of the survey data
      (N = 902) demonstrates a relatively strong and persistent relationship between
      management practices and employee psychological health. Interviews with a
      subsample of 54 workers reveal that management's excessive control, incompetence,
      and unresponsiveness, combined with minimal rewards for workers' efforts, left
      staff feeling devalued. Our findings suggest that workers' mental health was
      harmed by the undermining of their sense of self-worth and the loss of avenues to
      improve their working conditions.

PMID- 18831114
TI  - Death in birth.
AB  - The number of women in poor countries who die in childbirth has barely changed in
      two decades--and this despite a host of medical breakthroughs. How can the
      incidence of this devastating human tragedy be reduced?

PMID- 18831115
TI  - Life and death.
AB  - Advances in science are altering what it means to be human. So why aren't the
      candidates talking about it?

PMID- 18831116
TI  - Marshall Hall, the reflex arc and epilepsy.
AB  - Marshall Hall (1790-1857), who graduated from the University of Edinburgh's
      Medical School in 1812, was considered one of the greatest physiologists of his
      day. He advanced knowledge in various areas of medicine, in particular
      elucidating the mechanism of reflex activity in 1833. Hall suggested that
      convulsive epileptic seizures arose from heightened activity in the afferent limb
      or the central component of the reflex arc. From 1838 onwards he developed the
      idea that reflex-mediated neck muscle spasm in seizures obstructed cerebral
      venous return, congested the brain and thus caused unconsciousness. Associated
      reflex-mediated laryngeal spasm then caused convulsing. This was the most
      comprehensive physiologically based explanation of the major features of the
      convulsive epileptic seizure then available. Hall subsequently advocated and
      employed tracheotomy to prevent epileptic convulsing. His idea was taken up,
      modified and made more acceptable by others, and for a generation was the widely
      acknowledged basis for interpreting epileptogenesis. However, from 1870 onwards
      it was superseded by John Hughlings Jackson's accumulating evidence that
      epileptic seizures often arose in the cerebral cortex.

PMID- 18831117
TI  - A history of James Craig's hall for the Royal College of Physicians of Edinburgh.
AB  - The architectural history of the College's George Street hall, completed in 1781,
      has commonly been overlooked because it was demolished and deemed to have been a
      disappointment to both its owners and its architect, James Craig. This article
      reassesses the College's ambitions and Craig's efforts to match them, by
      accounting for the number of drawings which were made for the site and building,
      Craig's sources of inspiration and the building's appearance and influence. The
      paper reveals that the hall was actually intended to be part of a larger complex
      of buildings and rival Register House as the New Town's most impressive public
      edifice. The building has not been examined in this way before, and Craig's use
      of his library, drawing equipment and knowledge of London's architects and
      architecture are discussed to offer insight into his personal vision for the
      hall's appearance and meaning.

PMID- 18831118
TI  - Infant welfare, philanthropy and entrepreneurship in Glasgow: Sister Laura's
      Infant Food Company.
AB  - Laura Smith was sister-in-charge of the Children's Dispensary in Glasgow from
      1897 to 1922. In 1911 she established Sister Laura's Infant Food Company to
      market a special milk formula of her own invention.The directors of the
      Dispensary were not amused. As the 'outdoor' department of the Royal Hospital for
      Sick Children (Yorkhill), the Dispensary was at the forefront of efforts to
      combat child ill health and malnutrition. This paper considers Laura Smith's
      initiative within the context of the health and care of infants of the time -
      high infant mortality, public and professional concerns for infant welfare,
      technological advances in food science, changing recommendations and practices of
      infant feeding and ambiguous relations between medicine and commerce.

PMID- 18831119
TI  - The indefatigable Sir John Sinclair's Code of health.

PMID- 18831120
TI  - The way to save millions of lives is to prevent smoking.

PMID- 18831121
TI  - Feeding the 900 million: let them eat micronutrients.

PMID- 18831122
TI  - J. Michael Harrison (1915-2007): a research career well lived.

PMID- 18831123
TI  - Formation of partially and fully elaborated generalized equivalence classes.
AB  - Most complex categories observed in real-world settings consist of perceptually
      disparate stimuli, such as a picture of a person's face, the person's name as
      written, and the same name as heard, as well as dimensional variants of some or
      all of these stimuli. The stimuli function as members of a single partially or
      fully elaborated generalized equivalence class when they occasion the mutual
      selection of each other after the establishment of some subset of relations among
      the stimuli. Indeed, it is these generalized relations among stimuli that enable
      an individual to respond appropriately to the inevitable flux of natural
      environments. The present experiments involved procedures for producing both
      types of generalized equivalence class and for evaluating their retention.
      Granting the formal and functional similarities that exist between generalized
      equivalence classes and natural categories, natural kinds, and fuzzy
      superordinate classes, the variables responsible for the emergence of the former
      might also account for the emergence of the latter three phenomena. In Experiment
      1, After forming an A'-B' class, a B'-C relation was trained and generalization
      tests were conducted with B'-C, C-B', A'-C, and C'-A. Two of 5 participants
      passed the tests documenting the formation of A'-B'-C classes. Failures occurred
      in the A'-C and C-A' tests but not the B'-C and C-B' tests. Failures were also
      correlated with time between A'-B' class formation and C-based testing and with
      the absence of baseline confirmation when training and testing were separated by
      about one week. Experiment 2 replicated Experiment 1 but presented baseline
      confirmation probes immediatley prior to testing when training and testing were
      separated by one week; all participants then formed partially elaborated
      generalized equivalence classes. In Experiment 3, 5 of 6 participants formed
      fully elaborated generalized equivalence classes, represented as A' = B' = C'.

PMID- 18831124
TI  - Relative reinforcer rates and magnitudes do not control concurrent choice
      independently.
AB  - One assumption of the matching approach to choice is that different independent
      variables control choice independently of each other. We tested this assumption
      for reinforcer rate and magnitude in an extensive parametric experiment. Five
      pigeons responded for food reinforcement on switching-key concurrent variable
      interval variable-interval schedules. Across conditions, the ratios of reinforcer
      rates and of reinforcer magnitudes on the two alternatives were both manipulated.
      Control by each independent variable, as measured by generalized-matching
      sensitivity, changed significantly with the ratio of the other independent
      variable. Analyses taking the model-comparison approach, which weighs improvement
      in goodness-of-fit against increasing number of free parameters, were
      inconclusive. These analyses compared a model assuming constant sensitivity to
      magnitude across all reinforcer-rate ratios with two alternative models. One of
      those alternatives allowed sensitivity to magnitude to vary freely across
      reinforcer-rate ratios, and was less efficient than the common-sensitivity model
      for all pigeons, according to the Schwarz-Bayes information criterion. The second
      alternative model constrained sensitivity to magnitude to be equal for pairs of
      reinforcer-rate ratios that deviated from unity by proportionately equal amounts
      but in opposite directions. This model was more efficient than the common
      magnitude-sensitivity model for 2 of the pigeons, but not for the other 3. An
      analysis of variance, carried out independently of the generalized-matching
      analysis, also showed a significant interaction between the effects of reinforcer
      rate and reinforcer magnitude on choice. On balance, these results suggest that
      the assumption of independence inherent in the matching approach cannot be
      maintained. Relative reinforcer rates and magnitudes do not control choice
      independently.

PMID- 18831125
TI  - The reinforcing effects of houselight illumination during chained schedules of
      food presentation.
AB  - Pigeons' keypecking was maintained under two- and three-component chained
      schedules of food presentation. The component schedules were all fixed-interval
      schedules of either 1- or 2-min duration. Across conditions the presence of
      houselight illumination within each component schedule was manipulated. For each
      pigeon, first-component response rates increased significantly when the
      houselight was extinguished in the first component and illuminated in the second.
      The results suggest that the increase was not the result of disinhibition or
      modification of stimulus control by component stimuli, but appears to result from
      the reinforcement of responding by the onset of illumination in the second
      component. Additionally, the apparent reinforcing properties of houselight
      illumination resulted neither from association of the houselight with the
      terminal component of the chained schedule nor through generalization of the
      hopper illumination present during food presentation. The results of the present
      series of experiments are related to previous demonstrations of illumination
      reinforced responding and to the interpretation of data from experiments
      employing houselight illumination as stimuli associated with timeout or brief
      stimuli in second-order schedules.

PMID- 18831126
TI  - Tolerance to effects of cocaine on behavior under a response-initiated fixed
      interval schedule.
AB  - Tolerance to effects of cocaine can be modulated by schedules of reinforcement.
      With multiple ratio schedules, research has shown an inverse relationship between
      ratio requirement and amount of tolerance that resulted from daily administration
      of the drug. In contrast, tolerance to the effects of cocaine on behavior under
      multiple interval schedules generally has developed regardless of interval value.
      Under interval schedules reinforcement depends on the animal making one response
      following a time interval. Thus, as time to respond increases, the time to
      reinforcement decreases. On the other hand, fixed ratio schedules require a
      specified number of responses to be made prior to reinforcement. Therefore,
      delaying the initiation of responding does not coincide with a significant
      decrease in the time to reinforcement. In the current experiment, 6 pigeons were
      trained to respond under a three-component multiple schedule, with a different
      tandem fixed-ratio 1 fixed-interval schedule in each component. The multiple
      schedule required one response, which was followed by one of three fixed-interval
      values (5, 15, or 60 s). Thus, the multiple schedule was interval-like because
      after the fixed-ratio 1, only one more response was required for reinforcement,
      but it was also ratio-like because the length of the pause at the beginning of
      each interreinforcer interval affected the time until the next reinforcer. Acute
      administration of cocaine generally resulted in dose-dependent decreases in
      responding. Chronic (i.e., daily) administration of a rate-decreasing dose
      resulted in tolerance patterns similar to those usually obtained with multiple
      ratio schedules. That is, the magnitude of tolerance was related inversely to
      schedule size. These results suggest that delay to reinforcement from the initial
      response may play a role in the development of schedule-parameter-related
      tolerance.

PMID- 18831127
TI  - Individual differences, intelligence, and behavior analysis.
AB  - Despite its avowed goal of understanding individual behavior, the field of
      behavior analysis has largely ignored the determinants of consistent differences
      in level of performance among individuals. The present article discusses major
      findings in the study of individual differences in intelligence from the
      conceptual framework of a functional analysis of behavior. In addition to general
      intelligence, we discuss three other major aspects of behavior in which
      individuals differ: speed of processing, working memory, and the learning of
      three-term contingencies. Despite recent progress in our understanding of the
      relations among these aspects of behavior, numerous issues remain unresolved.
      Researchers need to determine which learning tasks predict individual differences
      in intelligence and which do not, and then identify the specific characteristics
      of these tasks that make such prediction possible.

PMID- 18831128
TI  - An inexpensive infrared detector to verify the delivery of food pellets.
AB  - The reproducibility of experimental outcomes depends on consistent control of
      independent variables. In food-maintained operant performance, it is of utmost
      importance that the quantity of food delivered is reliable. To that end, some
      commercial food pellet dispensers have add-on attachments to sense the delivery
      of pellets. Not all companies, however, offer such add-ons. Aside from
      availability, cost and temporary reduction in throughput may be a problem for
      smaller labs. The present paper outlines our recent development of a simple,
      inexpensive infrared device to detect and confirm the delivery of pellets. The in
      line construction of the detector routes the falling pellet through a barrel so
      that it passes between an infrared emitter and receiver. The circuitry was
      designed to be compatible with all commercially available behavioral measurement
      systems, and so may be retrofit to any existing system. Our tests with the
      detector so far have shown that it is 100% accurate in detecting pellet delivery.
      The individual unit cost is approximately 25 dollars. The low cost and
      versatility of the device offer an easy method to ensure the integrity of food
      delivery in operant settings.

PMID- 18831129
TI  - Conservatism, institutionalism, and the social control of intergroup conflict.
AB  - This research investigates the state social control of intergroup conflict by
      assessing the sociopolitical determinants of hate crime prosecutions. Consistent
      with insights from the political sociology of punishment, group-threat accounts
      of intergroup relations and the state, and neoinstitutional theory, the findings
      suggest that hate crime prosecutions are fewer where political conservatism,
      Christian fundamentalism, and black population size are higher, although this
      last effect is nonlinear. Linkages between district attorneys' offices and
      communities, on the other hand, increase hate crime prosecutions and the
      likelihood of offices' creating hate crime policies. Yet these policies are
      sometimes decoupled from actual enforcement, and such decoupling is more likely
      in politically conservative districts. The results indicate that common
      correlates of criminal punishment have very different effects on types of state
      social control that are protective of minority groups, and also suggest
      conditions under which policy and practice become decoupled in organizational
      settings.

PMID- 18831130
TI  - The context of discrimination: workplace conditions, institutional environments,
      and sex and race discrimination charges.
AB  - This article explores the organizational conditions under which discrimination
      charges occur. Drawing on structural and organizational theories of the
      workplace, the authors demonstrate how organizational conditions affect workers'
      and regulatory agents' understandings of unlawful discrimination. Using a
      national sample of work establishments, matched to discrimination-charge data
      obtained from the Equal Employment Opportunity Commission (EEOC), the authors
      examine how characteristics of the workplace and institutional environment affect
      variation in the incidence of workers' charges of sex and race discrimination and
      in the subset of discrimination claims that are verified by EEOC investigators.
      The findings indicate that workplace conditions, including size, composition, and
      minority management, affect workers' charges as well as verified claims; the
      latter are also affected by institutional factors, such as affirmative action
      requirements, subsidiary status, and industrial sector. These results suggest
      that internal workplace conditions affect both workers' and regulatory agents'
      interpretations of potentially discriminatory experiences, while institutional
      conditions matter only for regulatory agents' interpretations of those events.

PMID- 18831131
TI  - Geeks, meta-Geeks, and gender trouble: activism, identity, and low-power FM
      radio.
AB  - In this paper, I consider the activities of a group of individuals who tinker
      with and build radio hardware in an informal setting called 'Geek Group'. They
      conceive of Geek Group as a radical pedagogical activity, which constitutes an
      aspect of activism surrounding citizen access to low-power FM radio. They are
      also concerned with combating the gendered nature of hardware skills, yet in
      spite of their efforts men tend to have more skill and familiarity with radio
      hardware than women. Radio tinkering has a long history as a masculine
      undertaking and a site of masculine identity construction. I argue that this case
      represents an interplay between geek, activist, and gendered identities, all of
      which are salient for this group, but which do not occur together without some
      tension.

PMID- 18831132
TI  - Visions and versions of governing biomedicine: narratives on power structures,
      decision-making and public participation in the field of biomedical technology in
      the Austrian context.
AB  - In recent years, governance and public participation have developed into key
      notions within both policy discourse and academic analysis. While there is much
      discussion on developing new modes of governance and public participation, little
      empirical attention is paid to the public's perception of models, possibilities
      and limits of participation and governance. Building on focus group data
      collected in Austria within the framework of a European project, this paper
      explores lay people's visions and versions of government, governance and
      participation for two biomedical technologies: post-natal genetic testing and
      organ transplantation. Building on this analysis, we show that people situate
      their assessments of public participation against the background of rather
      complex lay models of the governance and government of the respective technology.
      Because these models are very different for the two technologies, participation
      also had very different connotations, which were deeply intertwined with each
      socio-technical system. Building on these findings we argue for a more technology
      sensitive approach to public participation.

PMID- 18831133
TI  - Medical science in the light of the Holocaust: Departing from a post-war paper by
      Ludwik Fleck.
AB  - In scholarly debates, Ludwik Fleck's post-war paper 'Problemy naukoznawstwa
      [Problems of the Science of Science]', published in 1946, has been taken
      unanimously to illustrate the epistemology expounded in his monograph Genesis and
      Development of a Scientific Fact. The paper has also been seen to support parts
      of the received view of Fleck, notably that he manufactured an anti-typhus
      vaccine while imprisoned in Buchenwald. However, a different narrative emerges
      when comparing Fleck's paper with other accounts, also published in 1946 and
      written by other prisoners alluded to by Fleck in his paper. The situation is
      further complicated by four papers, published in prestigious scientific journals
      between 1942 and 1945, by the German medical leader of the typhus studies
      accounted for by Fleck. In addition, a thus-far neglected paper by Fleck,
      published in 1946 and summarizing his observations on typhus, discloses his role
      in the Buchenwald studies. Despite the obvious difficulties with tracing the
      history behind these works, notably the one on Nazi science, the contention is
      that what was attempted in Buchenwald in the name of science amounted to
      pseudoscience. This conclusion is amply supported not only by the accounts given
      by Fleck's fellow prisoners, but also by his own post-war paper on typhus. Based
      on the above findings, it is suggested that the mythology about Fleck,
      established in the 1980s, has been accomplished by a selective reading of his
      papers and also that the role played by Fleck was more complex than has so far
      been contemplated.

PMID- 18831134
TI  - Locating therapeutic vaccines in nineteenth-century history.
AB  - This essay places some therapeutic vaccines, including particularly the
      diphtheria antitoxin, into their larger historical context of the late nineteenth
      century. As industrially produced drugs, these vaccines ought to be seen in
      connection with the structural changes in medicine and pharmacology at the time.
      Given the spread of industrial culture and technology into the field of medicine
      and pharmacology, therapeutic vaccines can be understood as boundary objects that
      required and facilitated communication between industrialists, medical
      researchers, public health officials, and clinicians. It was in particular in
      relation to evaluation and testing for efficacy in animal models that these
      medicines became a model for twentieth-century medicine. In addition, these
      medicines came into being as a parallel invention in two very distinct local
      cultures of research: the Institut Pasteur in Paris and the Institut fur
      Infektionskrankheiten in Berlin. While their local cultural origins were plainly
      visible, the medicines played an important role in the alignment of the methods
      and objects that took place in bacteriology research in France and Germany in the
      1890s. This article assesses the two locally specific regimes for control in
      France and in Imperial Germany. In France the Institut Pasteur, building on
      earlier successful vaccines, enjoyed freedom from scrutinizing control. The tight
      and elaborate system of control that evolved in Imperial Germany is portrayed as
      being reliant on experiences that were drawn from the dramatic events that
      surrounded the launching of a first example of so-called "bacteriological
      medicine," tuberculin, in 1890.

PMID- 18831135
TI  - Enacting cultural boundaries in French and German diphtheria serum research.
AB  - The experimental development of a therapeutic serum against diphtheria between
      1891 and 1894 was characterized by a scientific competition that pitted Emil
      Behring from the Institute for Infectious Diseases in Berlin against Emile Roux
      and Elie Metschnikoff from the Pasteur Institute in Paris. In general, their
      competition can be regarded as an extension of the fundamental differences that
      separated the research schools of Robert Koch and Louis Pasteur. However, to
      characterize the competition for a diphtheria-serum as "national rivalry" fails
      to account adequately for the mutual adoption of experimental practices by the
      Berlin and Parisian protagonists, whose contributions to the development of a
      therapeutic serum were intertwined in complex ways. Nor can it be characterized
      as "cooperation," given their fierce public disputes over scientific concepts and
      the fact that these disputes also shaped the peculiarities of the experimental
      procedures in Berlin and Paris. A close analysis reveals a complex picture of the
      dynamic interaction between the conceptual and experimental activities of
      Behring, Roux, and Metschnikoff- interaction that defined as well as bridged the
      "French" and "Prussian" experimental systems of diphtheria-serum research.

PMID- 18831136
TI  - Monitoring the stable at the Pasteur Institute.
AB  - Diphtheria serum production in France was dominated by the Pasteur Institute,
      which equipped a facility at Garches to produce the antitoxin on a large scale.
      This article treats the background to the founding of this facility, as well as
      its day-to-day functioning around 1900. The treatment integrates an examination
      of the practical undertaking of serum production by the Pasteur Institute with an
      analysis of the popular perception of the Institute and the mixed financing of
      the whole venture. We particularly emphasize the "industrial" features of this
      manufacturing process that involved living units of production, showing how
      bioassays influenced the destiny of the animals producing the serum. Finally, we
      argue that this monitoring of the horses, seen as serum-producing units, also
      provided information on the diseases the sera were intended to treat.

PMID- 18831137
TI  - The administrative stabilization of vaccines: Regulating the diphtheria antitoxin
      in France and Germany, 1894-1900.
AB  - It is well known that the development of a diphtheria anti-toxin serum evolved in
      a competitive race between two groups of researchers, one affiliated with Emil
      Behring in Berlin and Marburg, and another affiliated with Emile Roux in Paris.
      Proceeding on the basis of different theoretical assumptions and experimental
      practices, the two groups developed a therapeutic serum almost simultaneously.
      But the standardized substance they developed took on very different forms in the
      two countries. In Germany the new serum was marketed in the private sphere and
      subjected to state regulations, becoming a kind ofprototype of industrial
      medications. In France, however, the same substance was marketed as a gift of
      science to humanity and distributed through the communal health care system. This
      article demonstrates how a new medication emerged from the efforts to produce,
      market, regulate, distribute, and apply it in the two respective countries. It
      attributes the difference to the negotiations between the respective actors
      (scientists, industrialists, politicians, officers, and the public) and
      institutions (firms, academies, private and public institutes, legislative
      bodies, professional corporations). I develop this argument on three different
      levels: First, I stress the importance of the institutional foundations of serum
      production; second, I illustrate the decisive role played by existing "ways of
      regulating" in the rapid development of new legal statutes; and third, I describe
      the consequences that flowed from the respective administrative organization of
      marketing and dissemination. In sum, I explore how an experimental object was
      transformed into an object of the public health system and stabilized by
      administrative means.

PMID- 18831138
TI  - The dynamics of Wertbestimmung.
AB  - The procedure of Wertbestimmung played a vital role in the implementation of
      serum therapy and the standardization of mass-produced pharmaceuticals. In fin-de
      siecle Germany, a legal framework was put in place to guarantee serum quality and
      safety and to minimize any associated public health risks. Because the sera were
      biological remedies, it was difficult to produce them in uniform quality and the
      procedure of Wertbestimmung, i.e. determining the potency of the serum based on
      an objective and comparable value, was extremely complex. Various agents such as
      bacteria cultures, serum hosts, or test animals had to be regulated. In the years
      after 1895, numerous efforts to stabilize the procedures of Wertbestimmung were
      undertaken by serum producers and members of the state-run survey institute
      responsible for overseeing serum production. Despite efforts to stabilize the
      framework and to generate a reliable reference system, the framework's
      environment and agents were in constant flux: new producers entered the market
      and procedures were expanded to include other biologicals as well. The article
      describes the dynamics involved in the sustained efforts to maintain a stable
      framework in the face of constant alterations between 1895 and the 1920s.

PMID- 18831139
TI  - Producing, controlling, and stabilizing Pasteur's anthrax vaccine: creating a new
      industry and a health market.
AB  - When Pasteur and Chamberland hastily set up their small biological industry to
      meet the agricultural demand for the anthrax vaccine, their methods for
      preparation and production had not yet been stabilized. The process of learning
      how to standardize biological products was accelerated in 1882 when vaccination
      accidents required the revision of production norms as the first hypotheses on
      fixity, inalterability, and transportability of vaccines were invalidated and
      replaced by procedures for continuous monitoring of the calibration of vaccines
      and the renewal of vaccine strains. Initially, the incompleteness and ongoing
      development of production standards justified Pasteur's monopoly on the
      production of the anthrax vaccine under his immediate supervision. Later on, the
      Pasteur Institute maintained control of these standards in the framework of a
      commercial monopoly that it established on the veterinary vaccines first sent and
      then cultivated abroad by the Societe de Vulgarisation du Vaccin Charbonneux
      Pasteur, founded in 1886.

PMID- 18831140
TI  - Packaging BCG: standardizing an anti-tuberculosis vaccine in interwar Europe.
AB  - Using the example of the anti-tuberculosis vaccine BCG during the 1920s and
      1930s, this article asks how a labile laboratory-modified bacteria was
      transformed into a genuine standard vaccine packaged and commercialized as a
      pharmaceutical product. At the center of the analysis lies the notion of
      standardization inquiring why and how a local laboratory process with standard
      operating procedures (SOPs) reached its limits and was transformed when the
      product faced international distribution. Moving from Paul Ehrlich's initial
      technological notion of Wertbestimmung referring to a practice physiologically
      testing the effects of ill-defined antitoxins, the concept of standardization is
      extended to pharmaceutical and economical meanings implying quality control for
      biological therapeutic agents produced by a variety of industrial entrepreneurs.
      Following the request for product uniformity, two ways to maintain levels of
      compatibility and commonality are depicted opposing SOPs and end-product control.
      Furthermore, standardization is understood as a spiral, never ending process
      where progressive transformation of the vaccine in its production and medical
      uses periodically recreated the necessity of standardization. Developments
      analyzed are thus understood as a stabilization process aligning laboratory
      settings, products, and practices with medical theories and practices through
      technical, bureaucratic, and organizational systems. A paradox of the analysis is
      that standardization as a historical phenomenon and moment in the history of drug
      development was initially linked to a problem of under-determination of what was
      to be standardized and to a knowledge gap before it could become a central
      concept for quality control.

PMID- 18831141
TI  - Communication, control, and co-operation: (Latin) American interchanges in the
      history of international health.
AB  - This article discusses the development of historical studies of international
      health since the 1980s, showing that the field has gained considerable density
      and complexity. The authors touch on various current research trends in the
      history of international health, including reconsideration of so-called centre
      periphery and imperial-colonial relations. They emphasize the important, if often
      forgotten, role of Latin America in the history of international health and bring
      attention to the relevance of Canada to the international health field,
      especially in the last 30 years. The article concludes by introducing the
      articles that make up this special issue of CBMH, pointing out their most
      significant findings and cross-cutting themes.

PMID- 18831142
TI  - International health, the early cold war and Latin America.
AB  - This article offers a panoramic vision of the development of international health
      in Latin America during the late 1940s and the 1950s, when a series of bilateral
      and multilateral institutions, such as the World Health Organization and UNICEF,
      were founded and reshaped. The language, policies, and activities of these new
      institutional actors were heavily influenced by the context of the early Cold War
      between the era's superpowers: the United States and the Soviet Union. Vertical
      campaigns against yaws and malaria--implemented under the leadership of Fred L.
      Soper, director of the Pan American Sanitary Bureau--symbolized international
      health's technical orientation, as well as its contribution to the modernization
      of the countries of the region. The Cold War period has received little attention
      by historians of medicine, though it bears certain similarities to
      historiographical discussions of the relationship between tropical medicine and
      imperialism in the early 20th century.

PMID- 18831143
TI  - A Rockefeller Foundation health primer for US-occupied Nicaragua, 1914-1928.
AB  - The article presents views from above and below of the Rockefeller Foundation's
      International Health Commission's (IHC's) hookworm control program in Nicaragua
      from 1914 to 1928. It looks at the meaning, impact, and unique configuration of
      the Nicaraguan mission, while taking into account the larger global institutional
      project of this important international health actor. Although the IHC program in
      Nicaragua complemented some of the social policy goals of the US intervention in
      Nicaragua, which was a de facto protectorate during this period, the institution
      cannot be considered a direct expression or agent of US foreign policy.
      Ultimately the shape and limits of the IHC mission to Nicaragua were determined
      by the institutional project of the international public health agency itself,
      and by local considerations ranging from the characteristics of the staff to the
      response of rural communities to the anti-hookworm campaigns.

PMID- 18831144
TI  - Knowledge and power: the asymmetry of interests of Colombian and Rockefeller
      doctors in the construction of the concept of "jungle yellow fever," 1907-19381.
AB  - This study examines the asymmetries among the different interests of officials
      and medical doctors who worked for the Rockefeller Foundation and their Colombian
      counterparts in the development and consolidation of the concept of "jungle
      yellow fever," as distinguished from the known urban form of yellow fever. We
      explore the research responses to a variety of disease outbreaks in Colombia in
      the context of the Rockefeller campaigns against yellow fever, from the time of
      Roberto Franco's initial description of "yellow fever of the forests" in 1907
      until the consolidation of the concept of "jungle yellow fever" by Fred Soper in
      1938.

PMID- 18831145
TI  - [International policy (and the local response) and health in Brazil: the Special
      Public Health Service, 1942-1960].
AB  - This article analyzes the Special Public Health Service (SESP), a Brazilian
      American agency created in 1942. Envisioned by the United States as a temporary
      wartime organization, SESP was transformed into an instrument of expansion of
      Brazilian state authority via the interactions around and Brazilian responses to
      these activities. After 1945, SESP reoriented its aims and became a structured
      organization consisting of a permanent horizontal network of health units linked
      to the Brazilian government's nation-building project. Notwithstanding their
      international origins, SESP's health policies involved not only the importation
      of a US model to Brazil but also projects marked by adaptation to the local
      reality.

PMID- 18831146
TI  - Malaria and the emergence of rural health in Argentina: an analysis from the
      perspective of international interaction and co-operation.
AB  - At the end of the 19th century, after having long neglected sanitary conditions
      in rural areas, Argentinean public health authorities began to recognize the need
      to combat malaria in the country's northern provinces. The disease was
      proliferating among workers in the sugarcane and cotton industries, jeopardizing
      national and international economic interests. The crusade against malaria
      involved co-operation of the Argentinean, Brazilian, European, and US scientists,
      whose concerted efforts led to identification of the local characteristics of the
      disease and its mosquito vector. Argentina's antimalaria campaigns also derived
      from international interactions, but 19th-century European models proved hard to
      supplant. This study illustrates how malaria was established as an issue of
      public concern in Argentina in the early 20th century, highlighting the disease's
      socioeconomic dimensions and exploring the role of international sanitary co
      operation in paving the way for the establishment of a rural hygiene discourse.

PMID- 18831147
TI  - From autonomy to partial alignment: national malaria programs in the time of
      global eradication, Brazil, 1941-1961.
AB  - This article analyses the Brazilian experience in the battle against malaria from
      1941, when the Servico Nacional de Malaria (National Malaria Service) was created
      and a large-scale national program for malaria control begun, until the end of
      the Kubitscheck administration (1956-61) when Brazil joined the Global Malaria
      Eradication Program (MEP), led by the World Health Organization (WHO). We will
      discuss the relationship between the national program, aimed at controlling--and,
      in short order, eliminating--malaria using Brazilian strategies and methods and
      the international health organization's exclusively eradication-based program. Of
      particular importance is the role played by malariologist Mario Pinotti, who
      developed a special method for malaria control in the Amazon region, based on
      chloroquinated cooking salt, and who wielded tremendous political influence upon
      Brazil's public health path during the 1940s and 1950s. The article also
      highlights the implications of changes in Brazilian-US relations during the
      Kubitscheck term for Brazil's adoption of a malaria eradication program according
      to the WHO model.

PMID- 18831148
TI  - [Clinical and medical assistance in childbirth: trajectory of national and
      international influences, Santiago, Chile, 1900-1950].
AB  - This article outlines various aspects of the history of medical assistance for
      childbirth and its professionalization in Santiago, Chile, identifying the
      influences and interactions of Chilean medicine and national health and social
      policies with European clinical obstetrics and social medicine. It also explores
      the discussion and selective adoption and adaptation of these ideas by the Latin
      American scientific community and Chile's increasing interest in the US-developed
      field of public health specialization in the first half of the 20th century.

PMID- 18831149
TI  - Neighbours on notice: national and imperialist interests in the American Public
      Health Association, 1872-1921.
AB  - Since its founding in 1872, the American Public Health Association (APHA) has
      devoted its energies to influencing the US's federal, state, and local
      governments to support public health. But within a few years of its
      establishment, the APHA expanded its interests beyond US borders; Canada joined
      the organization in 1884, and Mexico and Cuba became members in 1892 and 1902,
      respectively. The organization acknowledged a name change to reflect its new
      membership--the American, Canadian, Mexican and Cuban Public Health Association.
      However, official control of the organization remained in US hands. This article
      explores the APHA's national and imperialist interests and the involvement of
      Canadian, Cuban, and Mexican public health professionals in the association. We
      seek to understand the economic, political, and medical factors that motivated
      the APHA to go beyond US borders and induced Canada, Mexico, and Cuba to join the
      organization. We examine the scope and limits of the APHA's success in obtaining
      first-hand information concerning epidemic and endemic diseases in each of its
      member countries and in imposing measures to prevent the spread of disease from
      one nation to another. We also discuss the impact of the APHA in urging the four
      countries to pass sanitary codes and establish active national departments of
      health. Finally, we analyze the role of Canadian, Mexican, and Cuban public
      health efforts in shaping the APHA and helping the organization understand the
      importance of reciprocity in international public health.

PMID- 18831150
TI  - Paul Natorp and the emergence of anti-psychologism in the nineteenth century.
AB  - This paper examines the anti-psychologism of Paul Natorp, a Marburg School Neo
      Kantian. It identifies both Natorp's principle argument against psychologism and
      the views underlying the argument that give it its force. Natorp's argument
      depends for its success on his view that certain scientific laws constitute the
      intersubjective content of knowledge. That view in turn depends on Natorp's
      conception of subjectivity, so it is only against the background of his
      conception of subjectivity that his reasons for rejecting psychologism make
      sense. This interpretation of Natorp suggests that attention paid to late
      nineteenth century theories of subjectivity and philosophy of psychology could
      improve our understanding of the emergence of anti-psychologism in that period.

PMID- 18831151
TI  - [Professionalization of public health officers in Japan].
AB  - In this paper, I describe how public health officers in Japan in the period of
      the late Taisho and early Showa eras claimed their position as professionals in
      the sanitary administrations of central and local governments. In the background
      of this push for recognition, there were related international and national
      movements. Internationally, public health ministries were established in
      developed countries and the League of Nations Health Organization (LNHO) was
      created. LNHO wanted to improve the level of public health officials world-wide,
      so the organization sponsored international exchanges of officials. These
      activities made a strong impression on Japanese public health officials, who
      realized that they belonged to an internationally recognized profession and that
      they needed to work hard to improve the substandard Japanese public health
      situation. Meanwhile, at the level of domestic politics, there were several
      movements of technical experts in different fields of government administration
      that worked to fight the unfair treatment of administrative officials, a
      situation that had existed since Meiji Period. The public health officers
      collaborated with the other technical experts to improve their positions and to
      play key roles in society. But while the other technical experts actively pursued
      social leadership, public health officials wanted to remain scientists. This is
      because the sanitary departments in the local governments were organized within
      police departments. In this environment, the law was dominant and science was
      secondary. But public health officials insisted that the basis of public health
      should be science, so they emphasized their scientific expertise.

PMID- 18831152
TI  - "Inhale it and see?" The collaboration between Thomas Beddoes and James Watt in
      pneumatic medicine.
AB  - The collaboration of Thomas Beddoes and James Watt in the development of
      pneumatic medicine--the treatment of disease by the breathing of airs--is well
      known but little understood. Its protagonists presented the venture as an
      empirical one, in which the efficacy of different airs was tested independently
      of theoretical considerations. Historians have generally accepted that claim at
      face value. We contend, on the contrary, that the divergent theoretical chemical
      commitments of Watt and Beddoes significantly shaped their different approaches
      to, and their interpretations and expectations of, the pneumatic project. In
      particular, Beddoes's broad adherence to Lavoisian chemistry gave him an oxygen
      centred approach to pneumatic medicine, while Watt's ongoing belief in phlogistic
      chemistry inclined him to expect great things of "hydrocarbonate." In addition,
      we show that a close examination of Watt's experiments and writings in his
      collaboration with Beddoes reveals a great deal about Watt's chemistry of airs.

PMID- 18831153
TI  - Stepping through science's door: C. W. Scheele, from pharmacist's apprentice to
      man of science.
AB  - This reinterpretation of Carl Wilhelm Scheele's (1742-86) early life and career
      analyses the social interplay between Scheele and other chemists who were active
      in eighteenth-century Sweden. It is argued that Scheele, a rather lowly
      journeyman working in peripheral pharmacies, had to work hard and traverse
      several geographical and social boundaries to gain a foothold in the scientific
      community. Eventually, Scheele's skilful analysis of the mineral magnesia nigra
      would establish him as one of the pivotal Swedish chemists. However, this
      happened only after Scheele had managed to prove himself as a knowledgeable
      chemist who did not threaten the authority of certain socially superior
      colleagues. When Scheele had gained a place in the scientific community, the
      exchange logic of the eighteenth-century republic of letters permitted him to
      trade experimental results for other kinds of resources. Hence, he gained in both
      social status, economic prosperity and scientific prominence in a relatively
      short time.

PMID- 18831154
TI  - Ira Remsen, saccharin, and the linear model.
AB  - While working in the chemistry laboratory at Johns Hopkins University, Constantin
      Fahlberg oxidized the 'ortho-sulfamide of benzoic acid' and, by chance, found the
      result to be incredibly sweet. Several years later, now working on his own, he
      termed this stuff saccharin, developed methods of making it in quantity, obtained
      patents on these methods, and went into production. As the industrial and
      scientific value of saccharin became apparent, Ira Remsen pointed out that the
      initial work had been done in his laboratory and at his suggestion. The ensuing
      argument, carried out in the courts of law and public opinion, illustrates the
      importance of the linear model to scientists who staked their identities on the
      model of disinterested research but who also craved credit for important
      practical results.

PMID- 18831155
TI  - Tissue engineering and regenerative medicine.

PMID- 18831156
TI  - Invisible floral larcenies: microbial communities degrade floral nectar of bumble
      bee-pollinated plants.
AB  - The ecology of nectarivorous microbial communities remains virtually unknown,
      which precludes elucidating whether these organisms play some role in plant
      pollinator mutualisms beyond minor commensalism. We simultaneously assessed
      microbial abundance and nectar composition at the individual nectary level in
      flowers of three southern Spanish bumble bee-pollinated plants (Helleborus
      foetidus, Aquilegia vulgaris, and Aquilegia pyrenaica cazorlensis). Yeasts were
      frequent and abundant in nectar of all species, and variation in yeast density
      was correlated with drastic changes in nectar sugar concentration and
      composition. Yeast communities built up in nectar from early to late floral
      stages, at which time all nectaries contained yeasts, often at densities between
      10(4) and 10(5) cells/mm3. Total sugar concentration and percentage sucrose
      declined, and percentage fructose increased, with increasing density of yeast
      cells in nectar. Among-nectary variation in microbial density accounted for 65%
      (H. foetidus and A. vulgaris) and 35% (A. p. cazorlensis) of intraspecific
      variance in nectar sugar composition, and 60% (H. foetidus) and 38% (A. vulgaris)
      of variance in nectar concentration. Our results provide compelling evidence that
      nectar microbial communities can have detrimental effects on plants and/or
      pollinators via extensive nectar degradation and also call for a more careful
      interpretation of nectar traits in the future, if uncontrolled for yeasts.

PMID- 18831157
TI  - Is spread of invasive species regulated? Using ecological theory to interpret
      statistical analysis.
AB  - We investigate a recent proposal that invasive species display patterns of
      spatial "spread regulation" analogous to density-dependent regulation of
      population abundances. While invasive species do offer valuable tests of
      ecological theories about spatial spread, we argue that the statistical approach
      used in the study is not useful, and that the proposed definition of "spread
      regulation" is likely to be confusing. While concepts of negative feedbacks in
      spatial spread may be reasonable, the proposed definition of "spread regulation"
      encompasses accelerating, constant, or decelerating spread. There is no
      compelling biological or practical reason to adopt such a definition. Moreover,
      we show that the statistical patterns (from time series of ratios of newly to
      recently invaded sites) proposed as evidence of spread regulation are predictable
      from basic diffusion models or other common models of constant spread with some
      stochasticity in dynamics and/or observations. Because such a wide range of
      processes would generate the observed patterns, no clear biological conclusions
      emerge from the proposed approach to spread analysis. When regarded in the
      context of the impacts and management of invasive species, the proposed
      regulation concept has the potential to create costly misunderstandings.

PMID- 18831158
TI  - Experimental warming shows that decomposition temperature sensitivity increases
      with soil organic matter recalcitrance.
AB  - Soil C decomposition is sensitive to changes in temperature, and even small
      increases in temperature may prompt large releases of C from soils. But much of
      what we know about soil C responses to global change is based on short-term
      incubation data and model output that implicitly assumes soil C pools are
      composed of organic matter fractions with uniform temperature sensitivities. In
      contrast, kinetic theory based on chemical reactions suggests that older, more
      resistant C fractions may be more temperature sensitive. Recent research on the
      subject is inconclusive, indicating that the temperature sensitivity of labile
      soil organic matter (OM) decomposition could either be greater than, less than,
      or equivalent to that of resistant soil OM. We incubated soils at constant
      temperature to deplete them of labile soil OM and then successively assessed the
      CO2-C efflux in response to warming. We found that the decomposition response to
      experimental warming early during soil incubation (when more labile C remained)
      was less than that later when labile C was depleted. These results suggest that
      the temperature sensitivity of resistant soil OM pools is greater than that for
      labile soil OM and that global change-driven soil C losses may be greater than
      previously estimated.

PMID- 18831159
TI  - Long-term reactions of plants and macroinvertebrates to extreme floods in
      floodplain grasslands.
AB  - Extreme summertime flood events are expected to become more frequent in European
      rivers due to climate change. In temperate areas, where winter floods are common,
      extreme floods occurring in summer, a period of high physiological activity, may
      seriously impact floodplain ecosystems. Here we report on the effects of the 2002
      extreme summer flood on flora and fauna of the riverine grasslands of the Middle
      Elbe (Germany), comparing pre- and post-flooding data collected by identical
      methods. Plants, mollusks, and carabid beetles differed considerably in their
      response in terms of abundance and diversity. Plants and mollusks, displaying
      morphological and behavioral adaptations to flooding, showed higher survival
      rates than the carabid beetles, the adaptation strategies of which were mainly
      linked to life history. Our results illustrate the complexity of responses of
      floodplain organisms to extreme flood events. They demonstrate that the
      efficiency of resistance and resilience strategies is widely dependent on the
      mode of adaptation.

PMID- 18831160
TI  - Janzen-Connell effects are widespread and strong enough to maintain diversity in
      grasslands.
AB  - Crop rotation schemes are believed to work by preventing specialist soil-borne
      pests from depressing the future yields of similar crops. In ecology, such
      negative plant-soil feedbacks may be viewed as a type of Janzen-Connell effect,
      which promotes species coexistence and diversity by preventing the same species
      from repeatedly occupying a particular site. In a controlled greenhouse
      experiment with 24 plant species and using soils from established field
      monocultures, we reveal community-wide soil-based Janzen-Connell effects between
      the three major functional groups of plants in temperate European grasslands. The
      effects are much stronger and more prevalent if plants are grown in interspecific
      competition. Using several soil treatments (gamma irradiation, activated carbon,
      fungicide, fertilizer) we show that the mechanism of the negative feedback is the
      buildup of soil pathogens which reduce the competitive ability of nearly all
      species when grown on soils they have formerly occupied. We further show that the
      magnitude of the change in competitive outcome is sufficient to stabilize
      observed fitness differences between functional groups in reasonably large
      communities. The generality and strength of this negative feedback suggests that
      Janzen-Connell effects have been underestimated as drivers of plant diversity in
      temperate ecosystems.

PMID- 18831161
TI  - Trait-mediated effects on flowers: artificial spiders deceive pollinators and
      decrease plant fitness.
AB  - Although predators can affect foraging behaviors of floral visitors, rarely is it
      known if these top-down effects of predators may cascade to plant fitness through
      trait-mediated interactions. In this study we manipulated artificial crab spiders
      on flowers of Rubus rosifolius to test the effects of predation risk on flower
      visiting insects and strength of trait-mediated indirect effects to plant
      fitness. In addition, we tested which predator traits (e.g., forelimbs, abdomen)
      are recognized and avoided by pollinators. Total visitation rate was higher for
      control flowers than for flowers with an artificial crab spider. In addition,
      flowers with a sphere (simulating a spider abdomen) were more frequently visited
      than those with forelimbs or the entire spider model. Furthermore, the presence
      of artificial spiders decreased individual seed set by 42% and fruit biomass by
      50%. Our findings indicate that pollinators, mostly bees, recognize and avoid
      flowers with predation risk; forelimbs seem to be the predator trait recognized
      and avoided by hymenopterans. Additionally, predator avoidance by pollinators
      resulted in pollen limitation, thereby affecting some components of plant fitness
      (fruit biomass and seed number). Because most pollinator species that recognized
      predation risk visited many other plant species, trait-mediated indirect effects
      of spiders cascading down to plant fitness may be a common phenomenon in the
      Atlantic rainforest ecosystem.

PMID- 18831162
TI  - When predators don't eat their prey: nonconsumptive predator effects on prey
      dynamics.

PMID- 18831163
TI  - Revisiting the classics: considering nonconsumptive effects in textbook examples
      of predator-prey interactions.
AB  - Predator effects on prey dynamics are conventionally studied by measuring changes
      in prey abundance attributed to consumption by predators. We revisit four classic
      examples of predator-prey systems often cited in textbooks and incorporate
      subsequent studies of nonconsumptive effects of predators (NCE), defined as
      changes in prey traits (e.g., behavior, growth, development) measured on an
      ecological time scale. Our review revealed that NCE were integral to explaining
      lynx-hare population dynamics in boreal forests, cascading effects of top
      predators in Wisconsin lakes, and cascading effects of killer whales and sea
      otters on kelp forests in nearshore marine habitats. The relative roles of
      consumption and NCE of wolves on moose and consequent indirect effects on plant
      communities of Isle Royale depended on climate oscillations. Nonconsumptive
      effects have not been explicitly tested to explain the link between planktonic
      alewives and the size structure of the zooplankton, nor have they been invoked to
      attribute keystone predator status in intertidal communities or elsewhere. We
      argue that both consumption and intimidation contribute to the total effects of
      keystone predators, and that characteristics of keystone consumers may differ
      from those of predators having predominantly NCE. Nonconsumptive effects are
      often considered as an afterthought to explain observations inconsistent with
      consumption-based theory. Consequently, NCE with the same sign as consumptive
      effects may be overlooked, even though they can affect the magnitude, rate, or
      scale of a prey response to predation and can have important management or
      conservation implications. Nonconsumptive effects may underlie other classic
      paradigms in ecology, such as delayed density dependence and predator-mediated
      prey coexistence. Revisiting classic studies enriches our understanding of
      predator-prey dynamics and provides compelling rationale for ramping up efforts
      to consider how NCE affect traditional predator-prey models based on consumption,
      and to compare the relative magnitude of consumptive and NCE of predators.

PMID- 18831164
TI  - Consumptive and nonconsumptive effects of predators on metacommunities of
      competing prey.
AB  - Although predators affect prey both via consumption and by changing prey
      migration behavior, the interplay between these two effects is rarely
      incorporated into spatial models of predator-prey dynamics and competition among
      prey. We develop a model where generalist predators have consumptive effects
      (i.e., altering the likelihood of local prey extinction) as well as
      nonconsumptive effects (altering the likelihood of colonization) on spatially
      separated prey populations (metapopulations). We then extend this model to
      explore the effects of predators on competition among prey. We find that
      generalist predators can promote persistence of prey metapopulations by promoting
      prey colonization, but predators can also hasten system-wide extinction by either
      increasing local extinction or reducing prey migration. By altering rates of prey
      migration, predators in one location can exert remote control over prey dynamics
      in another location via predator-mediated changes in prey flux. Thus, the effect
      of predators may extend well beyond the proportion of patches they visit. In the
      context of prey metacommunities, predator-mediated shifts in prey migration and
      mortality can shift the competition-colonization trade-off among competing prey,
      leading to changes in the prey community as well as changes in the susceptibility
      of prey species to habitat loss. Consequently, native prey communities may be
      susceptible to invasion not only by exotic prey species that experience reduced
      amounts of mortality from resident predators, but also by exotic prey species
      that exhibit strong dispersal in response to generalist native predators.
      Ultimately, our work suggests that the consumptive and nonconsumptive effects of
      generalist predators may have strong, yet potentially cryptic, effects on
      competing prey capable of mediating coexistence, fostering invasion, and
      interacting with anthropogenic habitat alteration.

PMID- 18831165
TI  - From individuals to ecosystem function: toward an integration of evolutionary and
      ecosystem ecology.
AB  - An important goal in ecology is developing general theory on how the species
      composition of ecosystems is related to ecosystem properties and functions.
      Progress on this front is limited partly because of the need to identify
      mechanisms controlling functions that are common to a wide range of ecosystem
      types. We propose that one general mechanism, rooted in the evolutionary ecology
      of all species, is adaptive foraging behavior in response to predation risk. To
      support our claim, we present two kinds of empirical evidence from plant-based
      and detritus-based food chains of terrestrial and aquatic ecosystems. The first
      kind comes from experiments that explicitly trace how adaptive foraging
      influences ecosystem properties and functions. The second kind comes from a
      synthesis of studies that individually examine complementary components of
      particular ecosystems that together provide an integrated perspective on the link
      between adaptive foraging and ecosystem function. We show that the indirect
      effects of predators on plant diversity, plant productivity, nutrient cycling,
      trophic transfer efficiencies, and energy flux caused by consumer foraging shifts
      in response to risk are qualitatively different from effects caused by reductions
      in prey density due to direct predation. We argue that a perspective of ecosystem
      function that considers effects of consumer behavior in response to predation
      risk will broaden our capacity to explain the range of outcomes and contingencies
      in trophic control of ecosystems. This perspective also provides an operational
      way to integrate evolutionary and ecosystem ecology, which is an important
      challenge in ecology.

PMID- 18831166
TI  - Leaf drop in evergreen Ceanothus velutinus as a means of reducing herbivory.
AB  - Conventional explanations for deciduousness do not include losses to herbivory.
      However, a recent explanation posits that deciduous leaf drop allows trees to
      reduce their herbivore loads and that this benefit of the deciduous habit may
      partly offset lost opportunities for photosynthesis. Much of the damage caused by
      chewing herbivores occurs early in the season when adult insects colonize as new
      leaves are expanding; trees without leaves from previous leaf flushes at this
      time are less attractive and suffer less cost of herbivory. I tested this
      hypothesis using Ceanothus velutinus, an evergreen shrub that shows considerable
      individual variation in leaf retention. Stems that held more leaves through
      winter experienced more chewing damage the following season. Stems with leaves
      experimentally removed through winter also were less likely to receive chewing
      damage the following season. At least some herbivores in this system make
      oviposition decisions before new leaves have expanded, and old leaves may provide
      cues about the suitability of the stem. Holding leaves through winter increased
      the likelihood of herbivory, and experimental protection from herbivores caused
      60% greater inflorescence production compared to unprotected stems. However, the
      cost of leaf retention was more than offset by an overall benefit. Stems that
      were allowed to keep winter leaves produced larger new leaves in summer and
      expanded them more rapidly in the season than stems with winter leaves
      experimentally removed. As a result, stems with leaves through winter experienced
      higher survival, four times as many inflorescences, and 40 times as many fruits
      as shoots that were experimentally defoliated. Losses to herbivores may be an
      unappreciated cost of leaf retention, and cost-benefit models of deciduous and
      evergreen behavior should include these losses.

PMID- 18831167
TI  - Selection toward shorter flowers by butterflies whose probosces are shorter than
      floral tubes.
AB  - Darwin's meticulous observations on the function of floral shape led to his
      famous prediction of a long-tongued pollinator, which he believed to be the
      evolutionary trigger for the long-spurred flowers of the Madagascar star orchid.
      Although tubular flowers are common, long tubes or spurs are an exception,
      suggesting that selection maintaining short flowers is widespread. Using the
      butterfly-pollinated carnation Dianthus carthusianorum and two butterfly species
      differing in proboscis length (Melanargia galathea and Inachis io) as model
      organisms, we experimentally demonstrate a reduction in pollinator efficiency
      with an increasing difference between proboscis length and floral tube length.
      Such a relationship is a prerequisite for the evolution of floral shape in
      response to pollinator morphology.

PMID- 18831168
TI  - Breeding systems and seed size in a neotropical flora: testing evolutionary
      hypotheses.
AB  - A well-known, but largely untested, prediction in plant reproductive ecology is
      that dioecious taxa should produce larger, more, higher-quality, or better
      defended seeds than cosexual taxa. Using a data set composed of 972 species in
      104 families, representing the flora of the Tambopata Wildlife Reserve (Madre de
      Dios, Peru), we evaluated the first component of this prediction, examining
      ecological and evolutionary relationships between breeding system and mean seed
      size with two kinds of tests. First, we conducted cross-species analyses to
      determine whether species with different breeding systems differed significantly
      with respect to mean individual seed size. Second, we used a hypothesized
      phylogeny to identify pairs of the most closely related taxa or clades within the
      Tambopata community that differed with respect to breeding system. Comparing pair
      members allowed us to determine whether evolutionary divergence in breeding
      system (between taxa with unisexual vs. cosexual individuals) was consistently
      associated with evolutionary change in seed size. In both analyses, we controlled
      for potentially confounding effects of growth form by examining these
      relationships within woody and nonwoody taxa. Cross-species analyses revealed
      that dioecious species produced larger seeds than cosexual species among woody
      species, shrubs, lianas (each growth form analyzed separately), and all species
      pooled, but not among trees. Phylogenetically independent contrasts upheld the
      significant association between breeding system and seed size among woody taxa,
      lianas, and all taxa pooled, but not among shrubs. We discuss the implications of
      our findings for evolutionary hypotheses regarding associations between dioecy
      and seed size.

PMID- 18831169
TI  - Nestedness of remnant sonoran desert plant communities in metropolitan Phoenix,
      Arizona.
AB  - Urbanization can have profound effects on the plant communities persisting in
      remnant habitats. That process can be explored by examining patterns of
      nestedness. Species composition for a set of communities exhibits a nested
      pattern if species present in progressively richer assemblages form a series of
      subsets. Nestedness can form as a result of the dynamic processes of extinction
      or colonization. It can also reflect a nested distribution of habitats among the
      sites or the differential abundance properties of species through passive
      sampling. This study investigated whether Sonoran Desert woody vegetation in
      remnant islands within metropolitan Phoenix is nested and explored which
      mechanisms are responsible for the pattern. It also examined whether vegetation
      is nested in similar habitat types across islands, and how species abundance
      relates to the nested pattern and hypothesized mechanisms. All data sets were
      significantly nested, indicating a nested pattern at the island and habitat
      levels. Community-level analyses did not indicate a primary mechanism leading to
      the nested pattern. Among species with abundances correlated with the nested rank
      order of sites, abundance properties were significantly related to different
      variables. This suggests that individual taxa respond to divergent ecological
      mechanisms, leading to nestedness. Thus, nestedness in plant communities can
      result from a complex set of contributors and may not be attributable to a single
      factor.

PMID- 18831170
TI  - Shifts in southern Wisconsin forest canopy and understory richness, composition,
      and heterogeneity.
AB  - We resurveyed the under- and overstory species composition of 94 upland forest
      stands in southern Wisconsin in 2002-2004 to assess shifts in canopy and
      understory richness, composition, and heterogeneity relative to the original
      surveys in 1949-1950. The canopy has shifted from mostly oaks (Quercus spp.)
      toward more mesic and shade-tolerant trees (primarily Acer spp.). Oak-dominated
      early-successional stands and those on coarse, nutrient-poor soils changed the
      most in canopy composition. Understories at most sites (80%) lost native species,
      with mean species density declining 25% at the 1-m2 scale and 23.1% at the 20-m2
      scale. Woody species have increased 15% relative to herbaceous species in the
      understory despite declining in absolute abundance. Initial canopy composition,
      particularly the abundance of red oaks (Quercus rubra and Q. velutina), predicted
      understory changes better than the changes observed in the overstory. Overall
      rates of native species loss were greater in later-successional stands, a pattern
      driven by differential immigration rather than differential extirpation. However,
      understory species initially found in early-successional habitats declined the
      most, particularly remnant savanna taxa with narrow or thick leaves. These losses
      have yet to be offset by compensating increases in native shade-adapted species.
      Exotic species have proliferated in prevalence (from 13 to 76 stands) and
      relative abundance (from 1.2% to 8.4%), but these increases appear unrelated to
      the declines in native species richness and heterogeneity observed. Although
      canopy succession has clearly influenced shifts in understory composition and
      diversity, the magnitude of native species declines and failure to recruit more
      shade-adapted species suggest that other factors now act to limit the richness,
      heterogeneity, and composition of these communities.

PMID- 18831171
TI  - Biomass rather than growth rate determines variation in net primary production by
      giant kelp.
AB  - Net primary production (NPP) is influenced by disturbance-driven fluctuations in
      foliar standing crop (FSC) and resource-driven fluctuations in rates of
      recruitment and growth, yet most studies of NPP have focused primarily on factors
      influencing growth. We quantified NPP, FSC, recruitment, and growth rate for the
      giant kelp, Macrocystis pyrifera, at three kelp forests in southern California,
      U.S.A., over a 54-month period and determined the relative roles of FSC,
      recruitment, and growth rate in contributing to variation in annual NPP. Net
      primary production averaged between 0.42 and 2.38 kg dry mass x m(-2) x yr(-1) at
      the three sites. The initial FSC present at the beginning of the growth year and
      the recruitment of new plants during the year explained 63% and 21% of the
      interannual variation observed in NPP, respectively. The previous year's NPP and
      disturbance from waves collectively accounted for 80% of the interannual
      variation in initial FSC. No correlation was found between annual growth rate
      (i.e., the amount of new kelp mass produced per unit of existing kelp mass) and
      annual NPP (i.e., the amount of new kelp mass produced per unit area of ocean
      bottom), largely because annual growth rate was consistent compared to initial
      FSC and recruitment, which fluctuated greatly among years and sites. Although
      growth rate was a poor predictor of variation in annual NPP, it was principally
      responsible for the high mean values observed for NPP by Macrocystis. These high
      mean values reflected rapid growth (average of approximately 2% per day) of a
      relatively small standing crop (maximum annual mean = 444 g dry mass/m2) that
      replaced itself approximately seven times per year. Disturbance-driven
      variability in FSC may be generally important in explaining variation in NPP, yet
      it is rarely examined because cycles of disturbance and recovery occur over
      timescales of decades or more in many systems. Considerable insight into how
      variation in FSC drives variation in NPP may be gained by studying systems such
      as giant kelp forests that are characterized by frequent disturbance and rapid
      rates of growth and recruitment.

PMID- 18831172
TI  - Offspring size variation within broods as a bet-hedging strategy in unpredictable
      environments.
AB  - Offspring size is strikingly variable within species. Although theory can account
      for variation in offspring size among mothers, an adaptive explanation for
      variation within individual broods has proved elusive. Theoretical considerations
      of this problem assume that producing offspring that are too small results in
      reduced offspring viability, but producing offspring that are too large (for that
      environment) results only in a lost opportunity for increased fecundity. However,
      logic and recent evidence suggest that offspring above a certain size will also
      have lower fitness, such that mothers face fitness penalties on either side of an
      optimum. Although theory assuming intermediate optima has been developed for
      other diversification traits, the implications of this idea for selection on
      intra-brood variance in offspring size have not been explored theoretically. Here
      we model the fitness of mothers producing offspring of uniform vs. variable size
      in unpredictably variable environments and compare these two strategies under a
      variety of conditions. Our model predicts that producing variably sized offspring
      results in higher mean maternal fitness and less variation in fitness among
      generations when there is a maximum and minimum viable offspring size, and when
      many mothers under- or overestimate this optimum. This effect is especially
      strong when the viable offspring size range is narrow relative to the range of
      environmental variation. To determine whether this prediction is consistent with
      empirical evidence, we compared within- and among-mother variation in offspring
      size for five phyla of marine invertebrates with different developmental modes
      corresponding to contrasting levels of environmental predictability. Our
      comparative analysis reveals that, in the developmental mode in which mothers are
      unlikely to anticipate the relationship between offspring size and performance,
      size variation within mothers exceeds variation among mothers, but the converse
      is true when optimal offspring size is likely to be more predictable. Together,
      our results support the hypothesis that variation in offspring size within broods
      can reflect an adaptive strategy for dealing with unpredictably variable
      environments. We suggest that, when there is a minimum and a maximum viable
      offspring size and the environment is unpredictable, selection will act on both
      the mean and variance of offspring size.

PMID- 18831173
TI  - Relative and interactive effects of plant and grazer richness in a benthic marine
      community.
AB  - The interactive effects of changing biodiversity of consumers and their prey are
      poorly understood but are likely to be important under realistic scenarios of
      biodiversity loss and gain. We performed two factorial manipulations of
      macroalgal group (greens, reds, and browns) and herbivore species (amphipods, sea
      urchin, and fish) composition and richness in outdoor mesocosms simulating a
      subtidal, hard-substratum estuarine community in North Carolina, U.S.A. In the
      experiment where grazer richness treatments were substitutive, there were no
      significant effects of algal or herbivore richness on final algal biomass.
      However, in the experiment in which grazer treatments were additive (i.e.,
      species-specific densities were held constant across richness treatments), we
      found strong independent and interactive effects of algal and herbivore richness.
      Herbivore polycultures reduced algal biomass to a greater degree than the sum of
      the three herbivore monocultures, indicating that the measured grazer richness
      effects were not due solely to increased herbivore density in the polycultures.
      Taking grazer density into account also revealed that increasing algal richness
      dampened grazer richness effects. Additionally, the effect of algal richness on
      algal biomass accumulation was far stronger when herbivores were absent,
      suggesting that grazers can utilize the increased productivity and mask the
      positive effects of plant biodiversity on primary production. Our results
      highlight the complex independent and interactive effects of biodiversity between
      adjacent trophic levels and emphasize the importance of performing biodiversity
      ecosystem functioning experiments in a realistic multi-trophic context.

PMID- 18831174
TI  - Habitat-mediated foraging limitations drive survival bottlenecks for juvenile
      salmon.
AB  - Realistic population models and effective conservation strategies require a
      thorough understanding of mechanisms driving stage-specific mortality. Mortality
      bottlenecks for many species occur in the juvenile stage and are thought to
      result from limitation on food or foraging habitat during a "critical period" for
      growth and survival. Without a way to account for maternal effects or to measure
      integrated consumption rates in the field, it has been virtually impossible to
      test these relationships directly. Hence uncertainties about mechanisms
      underlying such bottlenecks remain. In this study we randomize maternal effects
      across sites and apply a new method for measuring consumption integrated over
      weeks to months to test the hypothesis that food limitation drives early-season
      juvenile mortality bottlenecks in Atlantic salmon (Salmo salar). Using natural
      signatures of geologically derived cesium (133Cs), we estimated consumption rates
      of >400 fry stocked into six streams. Two to four weeks after stocking,
      consumption was extremely low across sites (0.005 g x g(-1) x d(-1)) and was
      predicted to be below maintenance rations (i.e., yielding negative energy
      balances) for the majority of individuals from five of six sites. However,
      consumption during this time was positively correlated with growth rates and
      survival (measured at the end of the growing season). In contrast, consumption
      rates increased in mid- (0.030 g x g(-1) x d(-1)) and late (0.035 g x g(-1) x d(
      1)) seasons, but juvenile survival and consumption were not correlated, and
      correlations between growth and consumption were weak. These findings are
      consistent with predictions of a habitat-based bioenergetic model constructed
      using the actual stream positions of the individual fish in the present study,
      which indicates that habitat-based models capture important environmental
      determinants of juvenile growth and survival. Hence, by combining approaches,
      reducing maternal effects and controlling initial conditions, we offer a general
      framework for linking foraging with juvenile survival and present the first
      direct consumption-based evidence for the early season bottleneck hypothesis.

PMID- 18831175
TI  - Benthic algal production across lake size gradients: interactions among
      morphometry, nutrients, and light.
AB  - Attached algae play a minor role in conceptual and empirical models of lake
      ecosystem function but paradoxically form the energetic base of food webs that
      support a wide variety of fishes. To explore the apparent mismatch between
      perceived limits on contributions of periphyton to whole-lake primary production
      and its importance to consumers, we modeled the contribution of periphyton to
      whole-ecosystem primary production across lake size, shape, and nutrient
      gradients. The distribution of available benthic habitat for periphyton is
      influenced by the ratio of mean depth to maximum depth (DR = z/ z(max)). We
      modeled total phytoplankton production from water-column nutrient availability,
      z, and light. Periphyton production was a function of light-saturated
      photosynthesis (BPmax) and light availability at depth. The model demonstrated
      that depth ratio (DR) and light attenuation strongly determined the maximum
      possible contribution of benthic algae to lake production, and the benthic
      proportion of whole-lake primary production (BPf) declined with increasing
      nutrients. Shallow lakes (z < or =5 m) were insensitive to DR and were dominated
      by either benthic or pelagic primary productivity depending on trophic status.
      Moderately deep oligotrophic lakes had substantial contributions by benthic
      primary productivity at low depth ratios and when maximum benthic photosynthesis
      was moderate or high. Extremely large, deep lakes always had low fractional
      contributions of benthic primary production. An analysis of the world's largest
      lakes showed that the shapes of natural lakes shift increasingly toward lower
      depth ratios with increasing depth, maximizing the potential importance of
      littoral primary production in large-lake food webs. The repeatedly demonstrated
      importance of periphyton to lake food webs may reflect the combination of low
      depth ratios and high light penetration characteristic of large, oligotrophic
      lakes that in turn lead to substantial contributions of periphyton to
      autochthonous production.

PMID- 18831176
TI  - Geographic variation in maternal investment: acidity affects egg size and
      fecundity in Rana arvalis.
AB  - Environmental-stress-mediated geographic variation in reproductive parameters has
      been little studied in natural vertebrate populations outside the context of
      climatic variation. Based on life-history theory, an increase in the degree of
      environmental stress experienced by a population should lead to (1) a shift in
      reproductive allocation from fecundity to offspring quality, (2) stronger trade
      offs between reproductive parameters, and (3) changes in the relationship between
      female phenotype and maternal investment. To test these predictions, we
      investigated geographic variation in maternal investment of moor frogs (Rana
      arvalis) in relation to breeding site acidity (pH 4-8). We found that mean egg
      size increased and clutch size and total reproductive output (TRO) decreased with
      increasing acidity among 19 Swedish moor frog populations. Tests for variation
      and co-variation in maternal investment and female size and age in 233 females
      from a subset of four acid origin (AO) and four neutral origin (NO) populations
      revealed that clutch size and TRO increased with female size in both acid and
      neutral environments. However, in AO populations, egg size also increased with
      female size, and clutch size and TRO with female age, whereas in NO populations,
      egg size increased with female age. The strength of the egg-size-clutch-size
      tradeoff tended to be stronger in AO than in NO females as expected if the former
      experience stronger environmental constraints. All in all, these results suggest
      that environmental acidification selects for investment in larger eggs at a cost
      to fecundity, imposes negative effects on reproductive output, and alters the
      relationship between female phenotype and maternal investment.

PMID- 18831177
TI  - Terrestrial habitat selection and strong density-dependent mortality in recently
      metamorphosed amphibians.
AB  - To predict the effects of terrestrial habitat change on amphibian populations, we
      need to know how amphibians respond to habitat heterogeneity, and whether habitat
      choice remains consistent throughout the life-history cycle. We conducted four
      experiments to evaluate how the spatial distribution of juvenile wood frogs, Rana
      sylvatica (including both overall abundance and localized density), was
      influenced by habitat choice and habitat structure, and how this relationship
      changed with spatial scale and behavioral phase. The four experiments included
      (1) habitat manipulation on replicated 10-ha landscapes surrounding breeding
      pools; (2) short-term experiments with individual frogs emigrating through a
      manipulated landscape of 1 m wide hexagonal patches; and habitat manipulations in
      (3) small (4-m2); and (4) large (100-m2) enclosures with multiple individuals to
      compare behavior both during and following emigration. The spatial distribution
      of juvenile wood frogs following emigration resulted from differences in the
      scale at which juvenile amphibians responded to habitat heterogeneity during
      active vs. settled behavioral phases. During emigration, juvenile wood frogs
      responded to coarse-scale variation in habitat (selection between 2.2-ha forest
      treatments) but not to fine-scale variation. After settling, however, animals
      showed habitat selection at much smaller scales (2-4 m2). This resulted in high
      densities of animals in small patches of suitable habitat where they experienced
      rapid mortality. No evidence of density-dependent habitat selection was seen,
      with juveniles typically choosing to remain at extremely high densities in high
      quality habitat, rather than occupying low-quality habitat. These experiments
      demonstrate how prediction of the terrestrial distribution of juvenile amphibians
      requires understanding of the complex behavioral responses to habitat
      heterogeneity. Understanding these patterns is important, given that human
      alterations to amphibian habitats may generate extremely high densities of
      animals, resulting in high density-dependent mortality.

PMID- 18831178
TI  - Intergenerational effects of climate generate cohort variation in lizard
      reproductive performance.
AB  - An evaluation of the link between climate and population dynamics requires
      understanding of climate effects both within and across generations. In
      ectothermic vertebrates, demographic responses to climate changes should
      crucially depend on balancing needs for heat and water. Here, we studied how
      temperature and rainfall regimes experienced before and during adulthood
      influenced reproductive performances (litter size, offspring size, and survival)
      in a natural population of the live-bearing common lizard, Lacerta vivipara,
      monitored continuously from 1989 to 2004. Rainfall regime, but not temperature,
      had both immediate and delayed effects on these reproductive performances.
      Rainfall during the first month of life was positively correlated with juvenile
      survival. Females experiencing more rainfall during gestation produced smaller
      neonates that showed greater survival when controlling for the positive effect of
      body size on survival. Furthermore, females that experienced heavier rainfall
      when in utero produced fewer but longer neonates during adulthood. These
      demographic effects of rainfall on adult reproductive traits may come from
      maternal effects of climate conditions and/or from delayed effects of rainfall on
      the environment experienced early in life. Irrespective of the precise mechanism,
      however, this study provides evidence of intergenerational climate effects in
      natural populations of an ectothermic vertebrate.

PMID- 18831179
TI  - Fecundity and survival in relation to resistance to oxidative stress in a free
      living bird.
AB  - Major life history traits, such as fecundity and survival, have been consistently
      demonstrated to covary positively in nature, some individuals having more
      resources than others to allocate to all aspects of their life history. Yet,
      little is known about which resources (or state variables) may account for such
      covariation. Reactive oxygen species (ROS) are natural by-products of metabolism
      and, when ROS production exceeds antioxidant defenses, organisms are exposed to
      oxidative stress that can have deleterious effects on their fecundity and
      survival. Using a wild, long-lived bird, the Alpine Swift (Apus melba), we
      examined whether individual red cell resistance to oxidative stress covaried with
      fecundity and survival. We found that males that survived to the next breeding
      season tended to be more resistant to oxidative stress, and females with higher
      resistance to oxidative stress laid larger clutches. Furthermore, the eggs of
      females with low resistance to oxidative stress were less likely to hatch than
      those of females with high resistance to oxidative stress. By swapping entire
      clutches at clutch completion, we then demonstrated that hatching failure was
      related to the production of low-quality eggs by females with low resistance to
      oxidative stress, rather than to inadequate parental care during incubation.
      Although male and female resistance to oxidative stress covaried with age, the
      relationships among oxidative stress, survival, and fecundity occurred
      independently of chronological age. Overall, our study suggests that oxidative
      stress may play a significant role in shaping fecundity and survival in the wild.
      It further suggests that the nature of the covariation between resistance to
      oxidative stress and life history traits is sex specific, high resistance to
      oxidative stress covarying primarily with fecundity in females and with survival
      in males.

PMID- 18831180
TI  - Chihuahuan Desert kangaroo rats: nonlinear effects of population dynamics,
      competition, and rainfall.
AB  - Using long-term data on two kangaroo rats in the Chihuahuan Desert of North
      America, we fitted logistic models including the exogenous effects of seasonal
      rainfall patterns. Our aim was to test the effects of intraspecific interactions
      and seasonal rainfall in explaining and predicting the numerical fluctuations of
      these two kangaroo rats. We found that logistic models fit both data sets quite
      well; Dipodomys merriami showed lower maximum per capita growth rates than
      Dipodomys ordii, and in both cases logistic models were nonlinear. Summer
      rainfall appears to be the most important exogenous effect for both rodent
      populations; models including this variable were able to predict independent data
      better than models including winter rainfall. D. merriami was also negatively
      affected by another kangaroo rat (Dipodomys spectabilis), consistent with
      previous experimental evidence. We hypothesized that summer rainfall influences
      the carrying capacity of the environment by affecting seed availability and the
      intensity of intraspecific competition.

PMID- 18831181
TI  - The demographic consequences of the cost of reproduction in ungulates.
AB  - The cost of reproduction can generate covariation between demographic rates that
      can potentially influence demography and population dynamics in long-lived
      iteroparous species. However, there has been relatively little work linking the
      survival cost of reproduction and population dynamics. The apparent scarcity of
      information on this important link is potentially due to covariation between
      vital rates, which can substantially influence fluctuations in population size.
      In this paper we examine the opportunity for survival costs of reproduction to
      leave a dynamic signature using a simulation model based broadly on an ungulate
      life history. We find that an increase in the cost delays the onset of
      reproduction and reduces reproductive rates of young, but not of prime-age,
      females. Accordingly, the number of offspring produced declines and the interval
      between reproductive events increases among young females experiencing high cost.
      These effects are translated to an age structure skewed toward young ages and
      reduced population density. These results suggest that, by delaying reproduction
      when conditions deteriorate, females protect their survival during the critical
      first three years of life, after which the negative effect of reproduction on
      survival declines. Unless conditions for reproduction are severe, it is not
      profitable to delay reproduction beyond age 3 years due to the high risk of death
      before having a chance to reproduce. We also demonstrate that lack of adjustment
      of reproductive strategies to elevated levels of the cost of reproduction, for
      example due to rapid changes in environmental conditions, results in lower
      average density and longevity compared to females that have sufficient time to
      adjust to changes in the cost. This suggests that even moderate costs of
      reproduction may have a major negative effect on population dynamics of
      ungulates.

PMID- 18831182
TI  - A general model for analyzing Taylor's spatial scaling laws.
AB  - Taylor's spatial scaling law concerns the relation between the variance and the
      mean population counts within areas of a given size. For a range of area sizes,
      the log of the variance often is an approximately linear function of the mean
      with a slope between 1 and 2, depending on the range of areas considered. In this
      paper, we investigate this relationship theoretically for random quadrat samples
      within a large area. The model makes a distinction between the local point
      process determining the position of each individual and the population density
      described by a spatial covariance function. The local point process and the
      spatial covariance of population density both contribute to the general
      relationship between the mean and the variance in which the slope may begin at 1,
      increase to 2, and decrease to 1 again. It is demonstrated by an example that the
      slope theoretically may exceed 2 by a small amount for very regular patterns that
      generate spatial covariance functions that increase in certain intervals. We also
      show how properties of population dynamics in space and time determine this
      relationship.

PMID- 18831183
TI  - Forward selection of explanatory variables.
AB  - This paper proposes a new way of using forward selection of explanatory variables
      in regression or canonical redundancy analysis. The classical forward selection
      method presents two problems: a highly inflated Type I error and an
      overestimation of the amount of explained variance. Correcting these problems
      will greatly improve the performance of this very useful method in ecological
      modeling. To prevent the first problem, we propose a two-step procedure. First, a
      global test using all explanatory variables is carried out. If, and only if, the
      global test is significant, one can proceed with forward selection. To prevent
      overestimation of the explained variance, the forward selection has to be carried
      out with two stopping criteria: (1) the usual alpha significance level and (2)
      the adjusted coefficient of multiple determination (Ra(2)) calculated using all
      explanatory variables. When forward selection identifies a variable that brings
      one or the other criterion over the fixed threshold, that variable is rejected,
      and the procedure is stopped. This improved method is validated by simulations
      involving univariate and multivariate response data. An ecological example is
      presented using data from the Bryce Canyon National Park, Utah, U.S.A.

PMID- 18831184
TI  - Nitrogen effects on decomposition: a five-year experiment in eight temperate
      sites.
AB  - The influence of inorganic nitrogen (N) inputs on decomposition is poorly
      understood. Some prior studies suggest that N may reduce the decomposition of
      substrates with high concentrations of lignin via inhibitory effects on the
      activity of lignin-degrading enzymes, although such inhibition has not always
      been demonstrated. I studied the effects of N addition on decomposition of seven
      substrates ranging in initial lignin concentrations (from 7.4% to 25.6%) over
      five years in eight different grassland and forest sites in central Minnesota,
      USA. I predicted that N would stimulate the decomposition of lignin-poor
      substrates but retard the decomposition of lignin-rich substrates. Across these
      sites, N had neutral or negative effects on decomposition rates. However, in
      contrast to my hypothesis, effects of N on decomposition were independent of
      substrate initial lignin concentrations, and decomposition of the lignin fraction
      was unaffected by N fertilization. Rather, substrate-site combinations that
      exhibited more rapid decomposition rates in the control treatment were affected
      more negatively by addition of N fertilization. Taken together, these results
      suggest that decreased decomposition with added N did not result from inhibition
      of lignin-degrading enzyme activity, but may have resulted from abiotic
      interactions between N fertilizer and products of microbial degradation or
      synthesis or from N effects on the decomposer community. Low initial substrate N
      concentrations and N fertilization both stimulated N immobilization, but the
      differences among substrates were generally much larger than the effects of
      fertilization. This study suggests that atmospheric N addition could stimulate
      ecosystem carbon sequestration in some ecosystems as a result of reduced rates of
      forest floor decomposition.

PMID- 18831185
TI  - Leaf herbivory and decomposability in a Malaysian tropical rain forest.
AB  - There is accumulating evidence that similar suites of plant traits may affect
      leaf palatability and leaf litter decomposability. However, the possible
      association between leaf herbivory and litter decomposition rates across species
      in species-diverse natural ecosystems such as tropical rain forests remains
      unexplored, despite its importance in estimating the herbivory effects on carbon
      and nutrient cycling of ecosystems. We found no strong association between leaf
      herbivory and litter decomposition rates across 40 tree species in a Malaysian
      tropical rain forest, even though the leaf and litter traits were tightly
      correlated. This is because the leaf and litter traits related to herbivory and
      decomposition rates in the field were inconsistent. Leaf toughness accounted for
      only a small part of the variation in the herbivory rate, whereas a number of
      litter traits (the leaf mass per area, lignin to nitrogen ratio, and condensed
      tannin concentration) accurately predicted the decomposition rate across species.
      These results suggest that herbivory rate across species may not be strongly
      related to single leaf traits, probably because plant-herbivore interactions in
      tropical rain forests are highly diverse; on the other hand, plant-decomposer
      interactions are less specific and can be governed by litter chemicals. We also
      investigated two factors, phylogeny and tree functional types, that could affect
      the relationship between herbivory and decomposition across species. Phylogenetic
      relatedness among the species did not affect the relationship between herbivory
      and decomposition. In contrast, when the plants were segregated according to
      their leaf emergence pattern, we found a significant positive relationship
      between herbivory and decomposition rates for continuous-leafing species. In
      these species, the condensed tannin to N ratios in leaves and litter were related
      to herbivory and decomposition rates, respectively. However, we did not observe a
      similar trend for synchronous-leafing species. These results suggest that the
      relationship between herbivory and decomposition may be more greatly affected by
      functional types than by phylogenetic relatedness among species. In conclusion,
      our results suggest that well-defended leaves are not necessarily less
      decomposable litter in a tropical rain forest community, implying that herbivory
      may not generate positive feedback for carbon and nutrient cycling in this type
      of ecosystem.

PMID- 18831186
TI  - Increasing litter species richness reduces variability in a terrestrial
      decomposer system.
AB  - Debate on the relationship between diversity and stability has been driven by the
      recognition that species loss may influence ecosystem properties and processes.
      We conducted a litterbag experiment in the Scottish Highlands, United Kingdom, to
      examine the effects of altering plant litter diversity on decomposition,
      microbial biomass, and microfaunal abundance. The design of treatments was fully
      factorial and included five species from an upland plant community (silver birch,
      Betula pendula; Scots' pine, Pinus sylvestris; heather, Calluna vulgaris;
      bilberry, Vaccinium myrtillus; wavy-hair grass, Deschampsia flexuosa); species
      richness ranged from one to five species. We tested the effects of litter species
      richness and composition on variable means, whether increasing litter species
      richness reduced variability in the decomposer system, and whether any richness
      variability relationships were maintained over time (196 vs. 564 days). While
      litter species composition effects controlled variable means, we revealed
      reductions in variability with increasing litter species richness, even after
      accounting for differences between litter types. These findings suggest that
      higher plant species richness per se may result in more stable ecosystem
      processes (e.g., decomposition) and decomposer communities. Negative richness
      variation relationships generally relaxed over time, presumably because
      properties of litter mixtures became more homogeneous. However, given that plant
      litter inputs continue to enter the belowground system over time, we conclude
      that variation in ecosystem properties may be buffered by greater litter species
      richness.

PMID- 18831187
TI  - Green hospitals: Improving the workplace, saving money, and healing the earth.

PMID- 18831188
TI  - Hospitals and the environment.
AB  - Think globally and act locally! This should not be viewed as a worn-out cliche
      because it is the call to action that has propelled Boulder Community Hospital to
      the forefront of those exemplary hospitals in the United States that have
      successfully executed environmentally friendly initiatives. It is this notion
      that inspired the leadership and staff at the hospital to initiate and embrace
      changes in their approach to eliminating waste. These achievements, by all
      measures, are nothing short of amazing.

PMID- 18831189
TI  - Demonstrating reverence for the earth.
AB  - As a community hospital and a major employer, St. Mary's Hospital Medical Center
      in Green Bay, Wisconsin, assumes responsibility not only for the health of people
      in the community but also for the health of the environment in which they live.
      Demonstrating reverence for the earth is a primary strategic goal, originating
      with its sponsoring organization, Hospital Sisters Health System, Springfield,
      Illinois. St. Mary's Hospital Medical Center is one of 13 hospitals in this
      system dedicated to healing ministries. Healing the earth is as important to this
      mission as is prevention and treatment to heal the human body. Over the past 25
      years, St. Mary's Hospital Medical Center has brainstormed and implemented
      innovative ideas to mend the earth, improving the health of air, water, and land,
      and ultimately improving the health of the people who come into contact with our
      dynamic environment. It is a passion and commitment of time and resources, but
      one in which there is no question that it is the right thing to do.

PMID- 18831190
TI  - Why should healthcare bother?

PMID- 18831191
TI  - The challenge of sustainable hospital building.

PMID- 18831192
TI  - Greening healthcare: 21st century and beyond.

PMID- 18831193
TI  - [Study on dynamic accumulation of flavone in various Chrysanthemum morifolium for
      medicine].
AB  - OBJECTIVE: To study the dynamic accumulation of flavonoids in Chrysanthemum
      morifolium in order to chose the optimal harvest time. METHOD: The flavonoid
      content was determined in various C. morifolium and in different periods. RESULT
      AND CONCLUSION: The accumulation of flavonoid in various Chrysanthemum reached a
      high level when lingulate flowers were in 50% blossom and tube ones in 30% or
      lingulate flowers were in 70% blossom and tube ones in 50%. Only few of C.
      morifolium reached a high level of flavonoid, when 1 both ingulate and tube
      flowers blossomed fully.

PMID- 18831194
TI  - [Effects of period of cuttage on growth of seedling for Lonicera japonica].
AB  - OBJECTIVE: To study the effect of cuttage time on growth of Lonicera japonica.
      METHOD: Randomized block of single variable and determination of the selected
      samples. RESULT: The growth of seeding influenced significantly by the cottage
      time. The experimental results in two years showed that the survival rate, the
      number of root, the root weight and root cap ratio that cuttaged on March 2 were
      better than those cuttaged at other time point. CONCLUSION: The first ten days of
      March is the best period for cuttaging L. japonica.

PMID- 18831195
TI  - [Study function of endophytic fungus in parasitism process of mistletoe].
AB  - OBJECTIVE: To research the function of endophytes of mistletoe in parasitism
      process of mistletoe in Pterocarya stenoptera. METHOD: Endophytes from eight
      different parts of the mistletoe were separated by explant culture, and further
      screened by different CMC plates culture and DNS method to get cellulase high
      productive strains. The distribution of the endophytic fungus parasitized in
      mistletoe were prepared and stained to demonstrate by histological section of the
      intumescentia part of the P. stenoptera. RESULT: The histological section
      indicated that aboundent of hyphasma were distributed around the haustorium of
      the mistletoe. Eighty three strains of endophytic fungus were separated, 38 of
      them were able to degrade cellulose, 19 strains showed high cellulase activity
      and 10 of which were separated from the parasitic position. CONCLUSION:
      Endophytic fungus of mistletoe can secrete cellulase and assist the haustorium of
      mistletoe to breakthrough the cell walls as well as intercellular space tissues
      of the P. stenoptera, thus, the endophytic fungus plays an important role in the
      parasitism process of mistletoe in P. stenoptera.

PMID- 18831196
TI  - [Study on seed germination testing standardization of Codonopsis tangshen].
AB  - OBJECTIVE: To study the influence of different factors (temperature, light and
      germinating beds) on seed germination of Codonopsis tangshen. METHOD: The general
      germination method was applied. RESULT AND CONCLUSION: The optimum seed
      germination conditions of C. tangshen were as follows: temperature 25 degrees C,
      light, germinating-beds top of paper (TP) or between of paper (BP). The first
      seedling--counting time was the 10th day after beginning the test; the final time
      was the 18th day. The test also showed that gibberellin notably increased the
      seed germination rate of C. tangshen.

PMID- 18831197
TI  - [Preparation and quality evaluation of intravenous tanshinone II (A) emulsion].
AB  - OBJECTIVE: To prepare and evaluate an intravenous emulsion of tanshinone II(A).
      METHOD: Soybean phospholipid mixing with poloxamer 188 was used as emulsifier.
      Oleic acid and glycerol were used as co-emulsifier and isoosmotic adjusting
      agent, respectively. The coarse emulsion was first prepared and following
      homogenization was carried out for the coarse emulsion by using a high pressure
      homogenizer. RESULT: The average diameter of the prepared tanshinone II (A)
      emulsion was 211 nm with a zeta potential of -32. 1 mV. There had no changes of
      diameter, zeta potential, pH value, content and physical appearance for the
      tanshinone II (A) emulsion stored at 25 degrees C away from light during one
      year. CONCLUSION: The physicochemical properties of the prepared tanshinone II
      (A) emulsion was stable, which could meet the requirements of intravenous
      administration.

PMID- 18831198
TI  - [Influence of different penetration enhancers on Lappaconitine transcutaneous
      permeation].
AB  - OBJECTIVE: To investigate the effects of different kinds and concentration of
      transdermal enhancers on Lappaconitine transcutaneous permeation when used
      individually or together. METHOD: Using modified Franz-type diffusion cell and
      excised human body skin as an in vitro transdermal model, the concentration of
      lappaconitine was determined by HPLC, then cumulative permeation quantity (Q) and
      stability rate (J) of progesterone were calculated. RESULT: Penetration enhancers
      such as propylene glycol, dodecanol, IPM, and particularly 3% OA and Azone, can
      significantly enhance the penetration rate of lappaconitine. Concentration effect
      of penetration enhancers concentration on lappaconitine transcutaneous permeation
      were found in experiments, the permeation effect of Azone was better than Azone +
      OA and Azone + propylene glycol. CONCLUSION: The transdermal rate of
      lappaconitine from batch which contains 3% OA or Azone is higher than others.
      Combination of Azone with other penetration enhancers is not recommended for
      Lappaconitine transcutaneous permeation.

PMID- 18831199
TI  - [Determination of apparent aqueous solubility and apparent oil-water partition
      coefficients of three bufadienolides composition].
AB  - OBJECTIVE: To investigate apparent aqueous solubility and apparent oil-water
      partition coefficients of three bufadienolides composition. METHOD: A high
      performance liquid chromatography method was established to determine apparent
      aqueous solubility of three bufadienolides composition; apparent oil-water
      partition coefficients of three bufadienolides composition was determined by
      shaking flask method. RESULT: The solubility of three bufadienolides composition
      reached the top value, 76.29 microg x mL(-1) (RBG), 51.85 microg x mL(-1) (CBG),
      32.76 microg x mL(-1) (BL) respectively and a total of 160.9 microg x mL(-1) in
      the condition of 37 degrees C and pH 7.0, therefore three bufadienolides
      composition can be defined as insoluble products. The solubility of the three
      decreased in weak acid or base environment to some extent. RBG, CBG, BL are
      liposoluble components and the sequence of log P is RBG > BL > CBG. CONCLUSION:
      RBG, CBG, BL is water-insoluble and hydrophobic. Surfactants can be applied to
      increase the solubility of three bufadienolides composition.

PMID- 18831200
TI  - [Study on the solubilization of O/W microemulsion for volatile oil].
AB  - OBJECTIVE: To study the solubilization of O/W microemulsion system for volatile
      oil. METHOD: Pseudo-ternary phase diagrams were prepared by using the method of
      titration, then investigating the solubilization of microemulsion system for
      different kind of volatile oil was investigated with the diagrams, and the effect
      of the formulation of microemulsion on the solubilization of Citrus sinensis oil
      were studied. RESULT: Kinds of volatile oil have an accelerated solubility in the
      microemulsion system. The species and dosage of oil phase and surfactant could
      influence the solubilization of microemulsion on Citrus sinensis oil. CONCLUSION:
      It is recommended to select a new method to solve the stabilization of volatile
      oil in the liquid preparation by the solubilization of suitable formulation of
      microemulsion.

PMID- 18831201
TI  - [Studies on active ingredients in Corydalis, broken cell wall corydalis and its
      processed products].
AB  - OBJECTIVE: To compare the contents of tetrahydropalmatine and dehydrocorydaline
      in corydalis, broken cell wall corydalis and its different processed products.
      METHOD: The broken cell wall technique was used to corydalis, and then both the
      corydalis and broken cell wall corydalis were processed. The method of
      chromatography which was used to determine the contents of tetrahydropalmatine
      and dehydrocorydaline in corydalis broken cell wall corydalis and its different
      processed products was performed by RP-HPLC with Kromasil ODS-C18 (4.6 mm x 250
      mm, 5 microm) column was used at 35 degrees C, acetonitrile-acetate buffer
      solution (pH 6.0) (30:70) as mobile phase of 1 mL x min(-1) flow rate, detection
      wavelength was set at 280 nm. RESULT: The contents of the two active components
      in broken cell wall corydalis were higher than that in corydalis, while that in
      broken cell wall and vinegar-fried corydalis was highest in the products of
      breaked cell wall corydalis. CONCLUSION: Breaking the cell wall of corydalis can
      help to dissolute alkaloids.

PMID- 18831202
TI  - [Optimization for extraction technology of polysaccharide in root of Adenophora
      potaninii from Taibai mountain in China by orthogonal experimental design].
AB  - OBJECTIVE: This study is to develop excellent extraction technology of the
      polysaccharides in the root of the A. potaninii which live in the Taibai Mountain
      in China. METHOD: Based on the extraction with water, the polysaccharides were
      deposited with alcohol. With the content of polysaccharides was as the index,
      extraction conditions were investigated systemly. Employed the solid-liquid
      ratio, extraction temperature, extraction time and extraction number of times
      were as levels of single factor, the optimal extraction technology of the
      polysaccharides from the root of the A. potaninii was determined by L9 (3(4))
      orthogonal experimental design L9 (3(4)). RESULT: The optimal technology
      conditions were that the solid-liquid ratio was 1 : 30, the extracting
      temperature was 60 degrees C, the extracting time was 3 h and extracting number
      of times was 3 times. CONCLUSION: The optimized extraction technology is simple,
      reliable and extraction efficiency of polysaccharide is higher.

PMID- 18831203
TI  - [Chemical constitutents in fermental mycelium of Xylaria nigripes].
AB  - Nine known compounds, 5-hydroxy-7-methoxy-2-methyl-4-chromanone (1), 5, 7
      dihydroxy-2-methyl-4-chromanone (2), 5-hydroxyl-2-methyl-4-chromanone (3), 1-(2,
      6-dihydroxyphenyl)-3-hydroxybutanone(4), 5alpha, 8alpha-epidioxyergosta-6, 22
      dien-3beta-ol (5), (22E,24R)-ergost-7, 22-dien-3beta, 5alpha, 6alpha-triol (6),
      euphorbol (7), beta-sitosterol (8) and 2-(4-hydroxyphenyl) -ethanol (9) were
      isolated and identified in Xylaria nigripes for the first time, and their
      structures were mainly determined by MS and NMR methods. Compounds 1 and 2 were
      isolated as the natural product for the first time.

PMID- 18831204
TI  - [Studies on chemical constituents of Dioscorea opposita].
AB  - OBJECTIVE: To study the chemical constituents of Dioscorea opposita. METHOD: The
      chemical constituents were isolated and purified by silica gel column
      chromatography, and the structures were elucidated by their spectroscopic data
      and physico-chemical properties. RESULT: Twelve compounds were obtained and
      identified as palmitic acid (1), beta-sitosterol (2), oleic acid (3), beta
      sitosterol acetate (4), 5-(hydroxymethyl)furfural (5), nonanedioic acid (6), beta
      daucosterol (7), cyclo-(Phe-Tyr) (8), cyclo-(Tyr-Tyr) (9), 6-methyl citrate (10),
      1, 5-dimethyl citrate (11), trimethyl citrate (12). CONCLUSION: Compounds 3-12
      were isolated from this plant for the first time and cyclodipeptides were firstly
      isolated from the Dioscoreae family; Compound 9 was a new natural product.

PMID- 18831205
TI  - [Studies on chemical constituents in n-butyl alcohol extract of roots of
      Actinidia deliciosa in Guangxi].
AB  - OBJECTIVE: To study the chemical constituents of n-butyl alcohol extract in the
      roots of Actinidia deliciosa in Guangxi. METHOD: The constituents were separated
      with various chromatographic techniques and their structures were elucidated by
      means of physicochemical properties and the analysis of their spectral data.
      RESULT: Six compounds were isolated and identified as eriantic acid B (1),
      2alpha, 3beta, 24-trihydroxyursa-12-en-28-oic acid (2), 2alpha, 3alpha, 24
      trihydroxyursa-12-en-28-oic acid (3), 2alpha, 3alpha, 23-tri-hydroxyursa-12, 20
      (30)-dien-28-oic acid (4), 2alpha, 3alpha, 24-trihydroxyursa-12, 20 (30)-dien-28
      oic acid (5), n-butyl-O-beta-D-fruto-pyranoside (6). CONCLUSION: Compounds 1-4, 6
      were obtained from this plant for the first time. Compound 6 was obtained from
      the genus Actinidia for the first time.

PMID- 18831206
TI  - [Study on antidepressant components of sucrose ester from Polygala tenuifolia].
AB  - OBJECTIVE: To investigate the antidepressant components of Polygala tenuifolia.
      METHOD: The chromatographic method was used to isolate and purify the chemical
      constituents, their structures were identified by spectral analysis, MTT method
      was applied to investigate their cytotoxic activities. RESULT: Nine compounds
      were isolated from the roots of P. tenuifolia. Their structures were identified
      as sibiricose A, (1), sibiricose A5 (2), tenuifoliside A (3) and 3', 6-disinapoyl
      sucrose (4), sibiricose A6 (5), 3, 4, 5-trimethoxycinnamate (6), polygalaxanthone
      III (7), tenuifolioses A (8), tenuifolioses H (9) and some compounds' activities
      to PC12 were observed. CONCLUSION: Compound 1 was isolated from this plant for
      the first time. Compounds 2,3 could protect PC12 cells damage induced by P.
      tenuifolia.

PMID- 18831207
TI  - [Identification of dihydroflavonol glycoside isomers in Smilax glabra by HPLC-MS
      and HPLC-1H NMR].
AB  - OBJECTIVE: To identify dihydroflavonol glycoside isomers in Smilax glabra.
      METHOD: The sample was analyzed by HPLC-MS in combination with HPLC-1H-NMR.
      RESULT: Four dihydroflavonol glycoside isomers were identified as astilbin,
      neoastilbin, isoastilbin, neoisoastilbin. CONCLUSION: The method is simple and
      rapid for the identification of dihydroflavonol glycosides in S. glabra.

PMID- 18831208
TI  - [Monosaccharide composition analysis and its content determination of
      polysaccharides from Rhaponticum uniforum].
AB  - OBJECTIVE: To analyze the monosaccharide composition in the polysaccharides from
      Rhaponticum uniforum, determine the content of monosaccharide, and provide some
      references for further research. METHOD: The monosaccharide composition was
      determined by high performance anion exchange chromatography with pulsed
      amperometric detection (HPAEC-PAD). Phenol-sulfuric acid method was used for the
      determination of the content of polysaccharide. RESULT: The monosaccharides
      composition in polysaccharides from R. uniforum are glucose, arabonose and
      fructose. Their molar ratios are 1 : 1.61 : 2.21. The content of polysaccharide
      is 95.78%, taking the mixture of monosaccharide compositions as reference
      substances. CONCLUSION: HPAEC-PAD can be used to analyze the monosaccharide
      composition in the polysaccharide with high precision, and the method of phenol
      sulfuric acid is simple, convenient and reliable.

PMID- 18831209
TI  - [Experiment of effective components from traditional Chinese herbs on ischemic
      left ventricular remodeling].
AB  - OBJECTIVE: To investigate the effects of effective components extracted from
      medicines compatibility on ischemic myocardial remodeling. METHOD: The animal
      models of ischemic myocardial remodeling was copied by ligating the left anterior
      descending branch of coronary artery in rat. And then decoction and effective
      components extracted from the same medicines were administrated to rats. The
      heart function was detected by ultrasound diagnostic apparatus and the heart
      morphology was examined by Hematoxylin and Eosin, picrosirius staining
      respectively on the 3rd and 56rd day. RESULT: Both concentrated decoction and
      effective components compatibility showed good restrained effects on ventricle
      malignant remodeling, such as improved heart function, reduced the area of
      myocardial infarction, lowered heart index, mitigated the fibrosis level and
      decreased apoptosis cell numbers in infarction and non-infarction areas. The
      difference were statistically significant when compared with the control group (P
      < 0.01, P < 0.05), and effective components treated group had better effects than
      concentrated decoction group (P < 0.05). Concentrated decoction group showed
      little effects on the 3rd day, while effective components group showed
      significant effect (P < 0.05). CONCLUSION: Effective components compatibility has
      better effects on inhibiting the process of ischemic myocardial remodeling than
      concentrated decoction. Effective components compatibility has better effects on
      ventricle malignant remodeling by eliminating the interfrence non-pharmacodynamic
      elements of the medicine.

PMID- 18831210
TI  - [Determination of plasma protein binding rate of methyl protodioscin with
      ultrafiltration].
AB  - OBJECTIVE: To study the plasma protein binding rate of methyl protodioscin.
      METHOD: The ultrafiltration was employed to determine the plasma protein binding
      rate of methyl protodioscin. The plasma concentrations of methyl protodioscin
      were measured by HPLC-MS-MS. RESULT: The plasma protein binding rate of methyl
      protodioscin with rat plasma at the concentration of 20.0, 100 and 200 microg x
      mL(-1) were (94.6 +/- 0.16)%, (91.6 +/- 0.35)% and (86.10 +/- 0.60)%,
      respectively, while the plasma protein binding rate of methyl protodioscin with
      normal human plasma at the above concentrations were (82.11 +/- 5.12)%, (84.54 +/
      0.32)% and (88.52 +/- 1.02)%, respectively. CONCLUSION: The binding rate of
      methyl protodioscin with plasma protein is high.

PMID- 18831211
TI  - [Study on pharmacokinetics of glycyrrhetic acid in rats by RP-HPLC].
AB  - OBJECTIVE: To develop a HPLC for the determination of plasma concentration of
      glycyrrhetic acid (GA) and study the pharmacokinetics of GA in rats. METHOD: To
      sample blood from rat which were injected GA by 1.0 mg x kg(-1) at 0.08, 0.17,
      0.25, 0.33, 0.5, 0.75, 1, 2, 3, 4, 6 h and use HPLC to determine the
      concentration of GA in it, the pharmaeokinetie parameters were accessed by DAS
      1.0. RESULT: The calibration curve was linear (r = 0.999 7) within the range of
      50-2 000 ng x mL(-1) for GA in plasma. The average recovery was (105.2 +/-
      2.23)%, (102.5 +/- 2.95)%, (98.4 +/- 2.32)%. The within-day and between-day
      derivation (RSD) were less than 4%. GA was fitted to a two compartment open
      pharmaeokinetie model in rats. The mainly pharmaeokinetie parameters were:
      t1/2alpha = (0.153 +/- 0.023) h, t1/2beta = (2.365 +/- 0.866) h, C(max) = (2.074
      +/- 0.100) mg x L(-1), CL = (0.715 +/- 0.082) L x h(-1) x kg(-1), V(d) = (2.427
      +/- 0.872) L x kg(-1), AUC(0-6 h) = (1.302 +/- 0.151) mg x h(-1) x L(-1).
      CONCLUSION: The method can be used to determine the concentration and to
      investigate the pharmacokinetics of GA in rat. GA was disposed extensively and
      rapidly in rats.

PMID- 18831212
TI  - [Inhibitory effects of Sanlengwan on aromatase and cyclooxygenase-2 in rats of
      endometriosis].
AB  - OBJECTIVE: To explore the effect mechanism of Sanlengwan (SLW) on estrogen
      production in ectopic endometrium of rats. METHOD: The rat model of endometriosis
      was established by surgical implant of endometrial tissue which belong to its
      body. Forty EMS model rats were randomly divided into five groups (n = 8): model
      control group, three different concentration SLW groups and anastrozole group.
      Meanwhile, eight normal rats were used as the normal control group. All the rats
      were treated for 4 weeks respectively, the changes of the P450 arom and
      cyclooxygenase-2 protein were measured by immunohistochemical test and western
      blot respectively before and after treatment of SLW, and the level of secretion
      of estrodiol and prostaglandin E2 was also measured by ECLIA and RIA. RESULT: SLW
      can reduce the expression of P450 arom protein, and the levels of estradiol after
      treatment of SLW were significantly lower than that of the model group in ectopic
      endometrial tissue (P < 0. 05); The high dose group of SLW can inhibit the
      expression of cyclooxygenase-2 protein and also reduce the production of
      prostaglandin E2 (P < 0.05). CONCLUSION: SLW can reduce the production of
      estradiol in the ectopic endometrial tissue of rats, and its mechanism might be
      associated with inhibiting the expression of P450 arom and interruption the
      positive feedback loop of estradiol production.

PMID- 18831213
TI  - [Effect of Bawei Xilei powder on CD3, CD4, CD8 T-lymphocytes of rats with
      ulcerative colitis].
AB  - OBJECTIVE: To observe the effect of Bawei Xilei powder on CD3, CD4, CD8 T
      lymphocytes in peripheral blood and colonic mucosa of rat with ulcerative
      colitis. METHOD: Sixty SD rats were randomly divided into 6 groups, normal group,
      model group, low, middle and high dosage Bawei Xilei powder group, Sulfasalazine
      group. Ulcerative colitis was induced by immunization with rabbit 's colonic
      mucous emulsified with completely Freund's adjuvant in all rats. Rats in low,
      middle and high dosage Bawei Xilei powder group were administered with 0.05, 0.1,
      0.2 mg Bawei Xilei powder for 18 days by enema respectively. While rats in
      Sulfasalazine group were enema administered with 100 mg Sulfasalazine, and the
      rats in other group were administered with equal volume of saline enema as
      control. We analyzed expression of CD3, CD4, CD8 T-lymphocytes in peripheral
      blood by flow cytometry and in colonic mucous by immunohistochemistry. RESULT: In
      peripheral blood, compared with normal group, in model group, the increased of
      CD4 T-lymphocytes and CD4 /CD8 ratio, the reduced of CD8 T-lymphocytes, these
      results were significant discrepancy (P < 0.01). Compared with model group, after
      treatment with Bawei Xilei powder, CD8 T-lymphocytes increased, but only high
      dosage Bawei Xilei powder group had discrepancy (P < 0.05). But low dosage Bawei
      Xilei powder group, other treatment groups' rats showed CD4/CD8 ratio were
      reduced significantly (P < 0.05). In colonic mucous, compared with normal group,
      in model group, Rats showed that expression of CD3, CD4 T-lymphocytes reduced and
      CD8 T-lymphocytes increased obviously (P < 0.05, P < 0.01). Compared with model
      group, expression of CD8 T-lymphocytes reduced significantly in all treatment
      groups (P < 0.05, P < 0.01). CONCLUSION: Bawei Xilei powder may regulate their
      balance between T-lymphocytes subgroup, consequently relieve inflammatory injury
      in favor of ulcer reparation and tissue regeneration.

PMID- 18831214
TI  - [Effects of Armillariella tabescens polysaccharide IPS-B2 on activity of mouse
      peritoneal macrophages and transcription of related gene].
AB  - OBJECTIVE: To observe the effect of IPS-B2 on mouse peritoneal macrophages and
      the transcription of IL-1beta, IL-6, TNF-alpha and iNOS. METHOD: ELISA method and
      Griess method were used to detect the effect of mouse peritoneal macrophages
      produce cytokines IL-1beta, IL-6, TNF-alpha and cytotoxic effectors NO. The
      transcription of IL-1beta, IL-6, TNF-alpha and iNOS was detected by real-time RT
      PCR method. RESULT: IPS-B2 could not promote mouse peritoneal macrophage
      production, but it could significantly improve the IL-1beta, IL-6, TNF-alpha
      content in mouse peritoneal macrophages culture supernatant, and increase the
      gene expression of IL-1beta, IL-6, TNF-alpha and iNOS. CONCLUSION: IPS-B2 can
      enhance the ability of peritoneal macrophages to excrete bioactive substances and
      promote the transcription of bioactive substances to antitumor.

PMID- 18831215
TI  - [Methodological study on quality evaluation of rhubarb based on purgative
      bioassay].
AB  - OBJECTIVE: To establish a method suitable to determine the purgative biopotency
      of rhubarb and construct a new quality evaluation pattern of rhubarb. METHOD: A
      series of factors such as observation index (mass of feces in 10 hours), animal
      strain (ICR mice), sex (male) and the dose of diphenoxylate complex (50 mg x kg(
      1)) was investigated and fixed. The purgative biopotency as well as anthraquinone
      determination was used to evaluate the quality of different rhubarb samples.
      RESULT: There wasn't a good linear relationship between the purgative biopotency
      and content of anthraquinone. The quality difference of rhubarb samples could be
      well characterized by combination of purgative biopotency determination and
      anthraquinone determination. CONCLUSION: The purgative biopotency determination
      can be used in quality control and evaluation of rhubarb.

PMID- 18831216
TI  - [Studies on anti-hyperglycemic effect and its mechanism of Clinopodium chinense].
AB  - OBJECTIVE: To investigate the anti-hyperglycemic effect and its mechanism of
      ethanol extraction from Calamintha chinensis (EJCT). METHOD: Fasting serum
      glucose (FSG) in normal mice was determined after oral administration of EJCT.
      Effects of EJCT on hyperglycemia mice induced by adrenaline were investigated by
      observing the contents of FSG and liver glucogen. Effect of EJCT on the diabetic
      mice induced by alloxan was investigated by observing the contents of FSG and the
      injured degree of pancreatic islet. The antilipid-peroxidation of EJCT on liver
      homogenate was measured by determination of malondiadehyde (MDA) induced by
      Fe2+/Cys. RESULT: EJCT showed no obvious effect on FSG in normal mice. However,
      EJCT 300, 600 mg x kg(-1) could remarkably decrease the contents of FSG and
      increase liver glucogen in hyperglycemia mice induced by adrenaline. In diabetic
      mice induced by alloxan, EJCT 150, 300, 600 mg x kg(-1) could remarkably decrease
      the contents of FSG. The damage of pancreatic islet induced by alloxan was also
      significantly attenuated by EJCT. Furthermore, EJCT 30, 60, 90, 120 mg x L(-1)
      inhibited lipid peroxidation initiated by Fe2+/Cys in liver homogenate.
      CONCLUSION: These results suggest that EJCT can significantly attenuate
      hyperglycemia in diabetic mice, which is probably due to decreasing the
      decomposition of liver glucogen, increasing the synthesis of liver glucogen,
      antioxidation and amelioration of damaged pancreatic islet.

PMID- 18831217
TI  - [Toxicological assessment on safety of water and 70% ethanolic extracts of nearly
      ripe fruit of Evodia rutaecarpa].
AB  - OBJECTIVE: To study the acute toxicity and mutagenic risk of the water extracts
      (ERWE) and 70% ethanol extracts (EREE) from the nearly ripe fruit of Evodia
      rutaecarpa, and provide experimental basis for safety evaluation of ones. METHOD:
      The ERWE and EREE were prepared from the nearly ripe fruit of E. rutaecarpa by
      reflux extraction with H2O and 70% ethanol aqueous solution for three times,
      respectively. According to the terms from "technical standards for test &
      toxicological assessment of health food" issued by Healthy Ministry of PRC, acute
      toxicity, and Ames, mouse marrow cell micronucleus and mouse sperm aberration
      test were performed. Acute toxicity test of ERWE and EREE in mice was studied by
      the method of Horn to give the median lethal dose (LD50). Forty healthy Kunming
      strain male and female mice were used and their body weights ranged from 17-22 g.
      All of them were distributed randomly to 4 different dose groups which each had
      10 mice. The ERWE or EREE was administered at the doses of 1.00, 2.15, 4.64 and
      10.00 g x kg(-1), respectively, via intragastrical route. The number of animals
      poisoned and died in each group were noted daily for 7 consecutive days. The Ames
      test was carried out using the Salmonella typhimurium strain TA97, TA98, TA100
      and TA102. In the sperm abnormalities test, 25 healthy adult male Kunming strain
      mice with a body weights ranged from 25-35 g were distributed randomly to 5
      different groups (1 positive control, 1 negative control and 3 treated groups)
      which each had 5 mice. A single dose of 60 g x kg(-1) of cyclophosphamide was
      intragastrically administered to mice in a positive control group, and the mice
      in the negative control group were administered with the same volume of distilled
      water. In the treated groups, the ERWE or EREE was intragastrically administered
      at the doses of 1.25, 250 and 5.00 g x kg(-1), respectively, via the same route
      with the positive control group. The administration was carried out once daily
      for 5 consecutive days. The sperm suspension was prepared from caudal epididymis
      of male mice at 35th day after treatment with different doses of the extract. The
      suspension was stained with Eosin-Y and air-dried smears were prepared. One
      thousand sperms per animal were analysed for abnormal shapes and the rates of
      sperm aberration was calculated. In the mouse bone marrow micronucleus assay, 50
      healthy adult male and female Kunming mice, weighing 25 to 30 g, were randomly
      assigned to five groups (1 positive control, 1 negative control and 3 treated
      groups) which each had 10 mice, five males and five females. The mice were
      intragastrically administered twice at intervals of 24 h with the ERWE or EREE at
      doses of 1.25, 2.50 and 5.00 g x kg(-1) in the positive control group. A single
      dose of 60 g x kg(-1) of cyclophosphamide in a positive control group and the
      same volume of distilled water in a negative control groups were intragastrically
      administered, respectively. Mouse bone marrow was obtained from 10 animals for
      each group at 6 h after the last dose administration. Smears were stained with
      Giemsa and analysed for the presence of mouse bone marrow micronucleus from 1 000
      cells. RESULT: The oral acute toxicity study in mice revealed that the LD50 of
      the both ERWE and EREE was more than 10.0 g x kg(-1). The mice with both the
      poisoned sign or died had not been observed after intragastrical administration
      of ERWE or EREE at the doses of 1.00, 2.15, 4.64 and 10.00 g x kg(-1). The
      results of genotoxicity tests were all negative, including Ames, mouse marrow
      cell micronucleus and mouse sperm aberration test. In the all assay in vivo, the
      mice showed a normally progressive increase in body weight from the start to the
      end of the experiment. CONCLUSION: The oral LD50 of the ERWE and EREE in mice was
      more than 10.0 g x kg(-1) belonging to non-toxicity on the acute toxicity rating
      criteria. The both ERWE and EREE showed no genotoxicity in the experimental
      condition.

PMID- 18831218
TI  - [Adverse drug reactions induced by Mailuoning injection: literature review on 162
      cases].
AB  - To understand the adverse drug reaction (ADR) induced by Mailuoning injection.
      162 ADRs due to the drug were retrieved from national medical journals of 1988
      2007 for statistics. It was shown that there was no relationship between ADR and
      dosage, but ADR appeared mostly in middle-aged and old groups, and more in male
      than in female. The occurrence of ADR was commonly within 30 min after injection.
      It involved injuries of various systems and organs. As for the 123 cases of
      allergy, 38 were anaphylactic shock (accounting for 23.46%), two people died. ADR
      characterized by immediate type on initial use and tachy type. It should be paid
      more attention to the Mailuoning injection for the immediate hypersensitivity
      reaction (such as anaphylactic shock).

PMID- 18831219
TI  - [Progress in Japanese herbal medicine in treatment of chronic kidney disease].
AB  - In Japan, Saireito and Onpi-to are widely used Japanese herbal medicine in the
      treatment of chronic kidney disease (CKD), which is a world-wide public health
      issue. In this review, it has been discussed the beneficial effects of Japanese
      herbal medicine, including Sairei-to and Onpi-to on multifarious renal damage in
      progression of CKD, such as mesangial lesion, inflammatory cell infiltration,
      cytokine expression, reactive oxygen species release, and aldosterone disorder,
      and then to clarify the mechanism of these herbs at molecular level by examining
      the effects on various injurious factors. Both Saireito and Onpi-to are effective
      agents for delaying the progression of CKD.

PMID- 18831220
TI  - [Modes and types of protecting natural resources of Chinese medicine].
AB  - To investigate a set of scientific and systematic methods for the sustainable
      utilization of natural resources of Chinese medicine. To summarize and review the
      studies on the reservation and sustainable using the resources of Chinese
      medicine. Five resource types, as well as the relevant reservation modes, are put
      forward for the Chinese medicine.

PMID- 18831221
TI  - Achieving the millennium development goals in Bangladesh.

PMID- 18831222
TI  - Achieving the millennium development goals for health and nutrition in
      Bangladesh: key issues and interventions--an introduction.

PMID- 18831223
TI  - Population challenges for Bangladesh in the coming decades.
AB  - Bangladesh currently has a population approaching 150 million and will add
      another 100 million before stabilizing, unless fertility can soon drop below
      replacement level. This level of fertility decline will require a change in
      marriage patterns, which have been minimal so far, even with increasing female
      schooling. It would also benefit from a long-awaited shift to long-term
      contraception. In addition to the consequence of huge population size, the
      density of population is already five times that of any other 'mega' country (>
      100 million), a very challenging situation for an agricultural society. Most of
      the future growth will be urban, increasingly in slums. Numbers of young people
      will not increase, but numbers of older people will increase 10-fold this
      century, creating a large burden on the health system, especially for chronic
      illnesses. High density of population means that agricultural land is virtually
      saturated, with very limited capacity to expand food production. Climate change
      may have dramatic impacts on agriculture, through flooding and drought resulting
      from weather changes and geopolitical influences on transborder rivers. Rising
      sea-levels and consequent salinity will affect crops and require shifts to
      alternative land use. Serious long-term planning is needed for meeting the
      growing needs of the population, both for distribution and consumption.

PMID- 18831224
TI  - Child health and mortality.
AB  - Bangladesh is currently one of the very few countries in the world, which is on
      target for achieving the Millennium Development Goal (MDG) 4 relating to child
      mortality. There have been very rapid reductions in mortality, especially in
      recent years and among children aged over one month. However, this rate of
      reduction may be difficult to sustain and may impede the achievement of MDG 4.
      Neonatal deaths now contribute substantially (57%) to overall mortality of
      children aged less than five years, and reductions in neonatal mortality are
      difficult to achieve and have been slow in Bangladesh. There are some interesting
      attributes of the mortality decline in Bangladesh. Mortality has declined faster
      among girls than among boys, but the poorest have not benefited from the
      reduction in mortality. There has also been a relative absence of a decline in
      mortality in urban areas. The age and cause of death pattern of under-five
      mortality indicate certain interventions that need to be scaled up rapidly and
      reach high coverage to achieve MDG 4 in Bangladesh. These include skilled
      attendance at delivery, postnatal care for the newborn, appropriate feeding of
      the young infant and child, and prevention and management of childhood
      infections. The latest (2007) Bangladesh Demographic and Health Survey shows that
      Bangladesh has made sustained and remarkable progress in many areas of child
      health. More than 80% of children are receiving all vaccines. The use of oral
      rehydration solution for diarrhoea is high, and the coverage of vitamin A among
      children aged 9-59 months has been consistently increasing. However, poor quality
      of care, misperceptions regarding the need for care, and other social barriers
      contribute to low levels of care-seeking for illnesses of the newborns and
      children. Improvements in the health system are essential for removing these
      barriers, as are effective strategies to reach families and communities with
      targeted messages and information. Finally, there are substantial health-system
      challenges relating to the design and implementation, at scale, of interventions
      to reduce neonatal mortality.

PMID- 18831225
TI  - Reducing maternal mortality and improving maternal health: Bangladesh and MDG 5.
AB  - Bangladesh is on its way to achieving the MDG 5 target of reducing the maternal
      mortality ratio by three-quarters between 1990 and 2015, but the annual rate of
      decline needs to triple. Although the use of skilled birth attendants has
      improved over the past 15 years, it remains less than 20% as of 2007 and is
      especially low among poor, uneducated rural women. Increasing the numbers of
      skilled birth attendants, deploying them in teams in facilities, and improving
      access to them through messages on antenatal care to women, have the potential to
      increase such use. The use of caesarean sections is increasing although not among
      poor, uneducated rural women. Strengthening appropriate quality emergency
      obstetric care in rural areas remains the major challenge. Strengthening other
      supportive services, including family planning and delayed first birth, menstrual
      regulation, and education of women, are also important for achieving MDG 5.

PMID- 18831226
TI  - Infectious diseases and vaccine sciences: strategic directions.
AB  - Despite substantial progress, infectious diseases remain important causes of ill
      health and premature deaths in Bangladesh. Bangladesh has experienced a > 90%
      reduction in the incidence of deaths due to childhood diarrhoea over the last 25
      years. Further reductions can be achieved through the introduction of effective
      vaccines against rotavirus and improvements in home hygiene, quality of drinking
      water, and clinical case management, including appropriate use of oral
      rehydration solution and zinc. Pneumonia is now the leading cause of childhood
      deaths in Bangladesh, and the pneumonia-specific child mortality is largely
      unchanged over the last 25 years. Reductions in mortality due to pneumonia can be
      achieved through the introduction of protein conjugate vaccines against
      Haemophilus influenza type b and Streptococcus pneumoniae, improvements in case
      management, including efforts to prevent delays in providing appropriate
      treatment, and the wider use of zinc. Tuberculosis is responsible for an
      estimated 70,000 deaths each year in Bangladesh. Although services for directly
      observed therapy have expanded markedly, improved case finding and involvement of
      private practitioners will be important to reduce the burden of disease.

PMID- 18831227
TI  - HIV and AIDS in Bangladesh.
AB  - Bangladesh initiated an early response to the HIV epidemic starting in the mid
      1980s. Since then, the response has been enhanced considerably, and many HIV
      prevention interventions among the most at-risk populations and the general youth
      are being undertaken. Alongside prevention activities, gathering of data has been
      a key activity fostered by both the Government and individual development
      partners. This paper reviews available sources of data, including routine
      surveillance (HIV and behavioural among most at-risk populations), general
      population surveys, and various research studies with the aim to understand the
      dynamics of the HIV epidemic in Bangladesh. Available data show that the HIV
      epidemic is still at relatively low levels and is concentrated mainly among
      injecting drug users (IDUs) in Dhaka city. In addition, when the passively
      reported cases were analyzed, another population group that appears to be
      especially vulnerable is migrant workers who leave their families and travel
      abroad for work. However, all sources of data confirm that risk behaviours that
      make individuals vulnerable to HIV are high--this is apparent within most at-risk
      populations and the general population (adult males and youth males and females).
      Based on the current activities and the sources of data, modelling exercises of
      the future of the HIV epidemic in Dhaka suggest that, if interventions are not
      enhanced further, Bangladesh is likely to start with an IDU-driven epidemic,
      similar to other neighbouring countries, which will then move to other population
      groups, including sex workers, males who have sex with males, clients of sex
      workers, and ultimately their families. This review reiterates the often repeated
      message that if Bangladesh wants to be an example of how to avert an HIV
      epidemic, it needs to act now using evidence-based programming.

PMID- 18831229
TI  - Micronutrients and anaemia.
AB  - Micronutrient deficiencies and anaemia remain as major health concerns for
      children in Bangladesh. Among the micronutrient interventions, supplementation
      with vitamin A to children aged less than five years has been the most
      successful, especially after distribution of vitamin A was combined with National
      Immunization Days. Although salt sold in Bangladesh is intended to contain
      iodine, much of the salt does not contain iodine, and iodine deficiency continues
      to be common. Anaemia similarly is common among all population groups and has
      shown no sign of improvement even when iron-supplementation programmes have been
      attempted. It appears that many other causes contribute to anaemia in addition to
      iron deficiency. Zinc deficiency is a key micronutrient deficiency and is covered
      in a separate paper because of its importance among new child-health
      interventions.

PMID- 18831228
TI  - Nutrition: basis for healthy children and mothers in Bangladesh.
AB  - Recent data from the World Health Organization showed that about 60% of all
      deaths, occurring among children aged less than five years (under-five children)
      in developing countries, could be attributed to malnutrition. It has been
      estimated that nearly 50.6 million under-five children are malnourished, and
      almost 90% of these children are from developing countries. Bangladesh is one of
      the countries with the highest rate of malnutrition. The recent baseline survey
      by the National Nutrition Programme (NNP) showed high rates of stunting,
      underweight, and wasting. However, data from the nutrition surveillance at the
      ICDDR,B hospital showed that the proportion of children with stunting,
      underweight, and wasting has actually reduced during 1984-2005. Inappropriate
      infant and young child-feeding practices (breastfeeding and complementary
      feeding) have been identified as a major cause of malnutrition. In Bangladesh,
      although the median duration of breastfeeding is about 30 months, the rate of
      exclusive breastfeeding until the first six months of life is low, and practice
      of appropriate complementary feeding is not satisfactory. Different surveys done
      by the Bangladesh Demographic and Health Survey, United Nations Children's Fund
      (UNICEF), and Bangladesh Breastfeeding Foundation (BBF) showed a rate of
      exclusive breastfeeding to be around 32-52%, which have actually remained same or
      declined over time. The NNP baseline survey using a strict definition of
      exclusive breastfeeding showed a rate of exclusive breastfeeding (12.8%) until
      six months of age. Another study from the Abhoynagar field site of ICDDR,B
      reported the prevalence of exclusive breastfeeding to be 15% only. Considerable
      efforts have been made to improve the rates of exclusive breastfeeding.
      Nationally, initiation of breastfeeding within one hour of birth, feeding
      colostrum, and exclusive breastfeeding have been promoted through the Baby
      Friendly Hospital Initiative (BFHI) implemented and supported by BBF and UNICEF
      respectively. Since most (87-91%) deliveries take place in home, the BFHI has a
      limited impact on the breastfeeding practices. Results of a few studies done at
      ICDDR,B and elsewhere in developing countries showed that the breastfeeding peer
      counselling method could substantially increase the rates of exclusive
      breastfeeding. Results of a study in urban Dhaka showed that the rate of
      exclusive breastfeeding was 70% among mothers who were counselled compared to
      only 6% who were not counselled. Results of another study in rural Bangladesh
      showed that peer-counselling given either individually or in a group improved the
      rate of exclusive breastfeeding from 89% to 81% compared to those mothers who
      received regular health messages only. This implies that scaling up peer
      counselling methods and incorporation of breastfeeding counselling in the
      existing maternal and child heath programme is needed to achieve the Millennium
      Development Goal of improving child survival. The recent data showed that the
      prevalence of starting complementary food among infants aged 6-9 months had
      increased substantially with 76% in the current dataset. However, the adequacy,
      frequency, and energy density of the complementary food are in question.
      Remarkable advances have been made in the hospital management of severely
      malnourished children. The protocolized management of severe protein-energy
      malnutrition at the Dhaka hospital of ICDDR,B has reduced the rate of hospital
      mortality by 50%. A recent study at ICDDR,B has also documented that home-based
      management of severe protein-energy malnutrition without follow-up was comparable
      with a hospital-based protocolized management. Although the community nutrition
      centres of the NNP have been providing food supplementation and performing growth
      monitoring of children with protein-energy malnutrition, the referral system and
      management of complicated severely-malnourished children are still not in place.

PMID- 18831230
TI  - Zinc treatment to under-five children: applications to improve child survival and
      reduce burden of disease.
AB  - Zinc is an essential micronutrient associated with over 300 biological functions.
      Marginal zinc deficiency states are common among children living in poverty and
      exposed to diets either low in zinc or high in phytates that compromise zinc
      uptake. These children are at increased risk of morbidity due to infectious
      diseases, including diarrhoea and respiratory infection. Children aged less than
      five years (under-five children) and those exposed to zinc-deficient diets will
      benefit from either daily supplementation of zinc or a 10 to 14-day course of
      zinc treatment for an episode of acute diarrhoea. This includes less severe
      illness and a reduced likelihood of repeat episodes of diarrhoea. Given these
      findings, the World Health Organization/United Nations Children's Fund now
      recommend that all children with an acute diarrhoeal illness be treated with
      zinc, regardless of aetiology. ICDDR.B scientists have led the way in identifying
      the benefits of zinc. Now, in partnership with the Ministry of Health and Family
      Welfare, Government of Bangladesh and the private sector, the first national
      scaling up of zinc treatment has been carried out. Important challenges remain in
      terms of reaching the poorest families and those living in remote areas of
      Bangladesh.

PMID- 18831231
TI  - Spousal violence in Bangladesh: a call for a public-health response.
AB  - Spousal violence against women is a serious public-health issue. Although there
      is a growing body of literature on this subject, there are still many unanswered
      questions regarding the prevalence of this violence, the risk factors, the
      consequences, and how to address the issue. The purpose of this literature review
      is to organize and synthesize the empirical evidence on spousal violence against
      women in Bangladesh and to provide direction for both researchers and
      practitioners for future work in this area. The review suggests that spousal
      violence against women is high in Bangladesh. The list of correlates is long and
      inconclusive. Although there is evidence on adverse consequences of this violence
      on health of women and their children, more research is needed to explore the
      multifaceted consequences of violence for women, children, families, and
      communities. Action research is needed to develop and test preventive and
      curative interventions.

PMID- 18831232
TI  - Action monitoring for equity and gender in health.
AB  - Equity and gender, despite being universal concerns for all health programmes in
      Bangladesh, are often missing in many of the health agenda. The health programmes
      fail to address these important dimensions unless these are specifically included
      in the planning stage of a programme and are continually monitored for progress.
      This paper presents the situation of equity in health in Bangladesh, innovations
      in monitoring equity in the use of health services in general and by the poor in
      particular, and impact of targeted non-health interventions on health outcomes of
      the poor. It was argued that an equitable use of health services might also
      result in enhanced overall coverage of the services. The findings show that
      government services at the upazila level are used by the poor proportionately
      more than they are in the community, while at the private facilities, the
      situation is reverse. Commonly-used monitoring tools, at times, are not very
      useful for the programme managers to know how well they are doing in reaching the
      poor. Use of benefit-incidence ratio may provide a quick feedback to the health
      facility managers about their extent of serving the poor. Similarly, Lot Quality
      Assurance Sampling can be an easy-to-use tool for monitoring coverage at the
      community level requiring a very small sample size. Although health problems are
      biomedical phenomena, their solutions may include actions beyond the biomedical
      framework. Studies have shown that non-health interventions targeted towards the
      poor improve the use of health services and reduce mortality among children in
      poor households. The study on equity and health deals with various interlocking
      issues, and the examples and views presented in this paper intend to introduce
      their importance in designing and managing health and development programmes.

PMID- 18831233
TI  - An early sixteenth century optometrist 's shop: Jacob Cornelisz. van Oostsanen's
      "Lx siin tiid".
AB  - In Jacob Cornelisz. van Oostsanen's early Dutch painting (ca. 1511-1514), an
      elderly gentleman hands a pair of spectacles to a young woman within a richly
      filled interior. Although the painting has acquired various names and is
      described more generally as a genre piece, no research has considered its
      specific imagery and the reason for its commission. This article argues that the
      painting depicts an early sixteenth century eyeglass maker's shop and may even be
      the earliest known advertisement for such an establishment.

PMID- 18831234
TI  - William Molyneux and the optometry content of his 1692 book Dioptrica Nova.
AB  - This paper provides an overview of the life of William Molyneux (1656-1698) and
      his book Dioptrica Nova, published in 1692. The first part of that book examines
      the geometrical optics of lenses, the eye, telescopes, and microscopes. The
      second part consists of commentaries on various topics, including spectacles,
      telescopes, and physiological diplopia.

PMID- 18831235
TI  - Catalytic upgrading of biomass fast pyrolysis oils.

PMID- 18831236
TI  - Green oxidation of renewable carbohydrates: lactobionic acid production as an
      example.

PMID- 18831237
TI  - Microalgae and the biological sunlight-to-biogas energy conversion system.

PMID- 18831238
TI  - The use of bio-energy crops for phytoremediation of metal enriched soils in the
      Campine region.

PMID- 18831239
TI  - Influence of the polar content of used cooking oils on the biodiesel quality.

PMID- 18831240
TI  - Optimizing Arabidopsis thaliana as a platform for the seed-based production of
      recombinant proteins.

PMID- 18831241
TI  - The study of hydrophobic proteins of Arabidopsis thaliana and banana, a model and
      non model crop.

PMID- 18831242
TI  - Genes controlling the formation of unreduced pollen in Arabidopsis thaliana a
      forward genetics approach.

PMID- 18831243
TI  - Fluorescence in situ hybridization (FISH) to elucidate structure and diversity in
      granular biomass for the treatment of nitrogenous wastewater.

PMID- 18831244
TI  - Shedding light on biofilm formation.

PMID- 18831245
TI  - Healthy milk and meat through forage.

PMID- 18831246
TI  - Manipulating the combined pressure-temperature stability of alpha-amylases from
      Bacillus species in the high pressure pasteurization range by the use of solvent
      engineering.

PMID- 18831247
TI  - Modelling the growth/no growth boundary of spoilage microorganisms in foods as an
      alternative method to preserve products without using chemical preservatives.

PMID- 18831248
TI  - Inhibition of salmonella biofilm formation: a sustainable alternative in the
      production of safe and healthy food.

PMID- 18831249
TI  - Genrisk-T project: response of the TPC-1 papillary thyroid carcinoma cell line to
      a range of low to high doses of irradiation.

PMID- 18831250
TI  - The anode potential regulates the bacterial activity in microbial fuel cells.

PMID- 18831251
TI  - Existence of non-uniformity in 3d spatio-temporal distribution of airspace and
      product temperatures inside meat cooking chambers.

PMID- 18831252
TI  - Inactivation of murine norovirus 1 and Bacteroides fragilis infecting phage B40-8
      by the use of sodium hypochlorite and peroxyacetic acid as decontaminating agents
      for shredded iceberg lettuce.

PMID- 18831253
TI  - Effects of simulated space conditions on foetal mouse fibroblasts.

PMID- 18831254
TI  - Bio-flocs technology for overwintering of tilapia.

PMID- 18831255
TI  - Changes induced in whey protein due to interactions with lipids.

PMID- 18831256
TI  - In vitro rumen biohydrogenation of trans-10, cis-12 conjugated linoleic acid in a
      lipid-encapsulated (LE-CLA) supplement incorporated or not in a processing
      pellet.

PMID- 18831257
TI  - Assessment of technical mitigation measures in the ecosystem approach to
      fisheries management.

PMID- 18831258
TI  - Sequential batch reactors as an alternative approach for bio-flocs technology in
      aquaculture: from waste to fish.

PMID- 18831259
TI  - A preliminary mechanistic model for simulation of tomato fruit production.

PMID- 18831260
TI  - The use of chlorophyll fluorescence imaging to evaluate the effect of cold stress
      for industrial chicory.

PMID- 18831261
TI  - Outdoor performance of coated wooden window frames as a basis for service life
      prediction.

PMID- 18831262
TI  - Effect of maximum packing limit on granular flow pattern in the top-spray
      fluidised bed coater.

PMID- 18831263
TI  - On the origin of kiwifruit: classifying kiwifruit from different countries using
      VIS/NIR spectroscopy.

PMID- 18831264
TI  - Effects of different inclusion levels of oil palm fronds on in vitro short chain
      fatty acid and methane productions, and on rumen biohydrogenation.

PMID- 18831265
TI  - Heavy metal availability in soil in the presence of anionic surfactants.

PMID- 18831266
TI  - Hypochlorite-induced oxidation of dairy proteins: impact of pH and oxidant
      concentration.

PMID- 18831267
TI  - Assessment of the effectiveness of food safety management systems in food
      industries.

PMID- 18831268
TI  - Maximum removal rate of propionic acid as sole carbon source in UASB reactors by
      macro and micro nutrients stimulation.

PMID- 18831269
TI  - Ascorbic acid biosynthesis during tomato fruit development and ripening.

PMID- 18831270
TI  - Agro-climatic assessment of the rainy season for maize production in the maize
      belt of Zimbabwe.

PMID- 18831271
TI  - Fast quantification of total volatile bases and other volatile microbial spoilage
      metabolites formed in cod fillets using SIFT-MS technology.

PMID- 18831272
TI  - Medium-chain fatty acids from coconut oil or krabok oil to reduce in vitro rumen
      methanogenesis.

PMID- 18831273
TI  - Field evaluation of the interaction common bean genotype, rhizobacteria and
      environmental factors in Cuba.

PMID- 18831274
TI  - Biocontrol of Pseudomonas savastanoi, causative agent of olive knot disease:
      antagonistic potential of non-pathogenic rhizosphere isolates of fluorescent
      Pseudomonas.

PMID- 18831275
TI  - Quantification of B3GNT5 and B4GALT4 expression reveals no difference between
      piglets with or without diarrhea.

PMID- 18831276
TI  - Sensitivity of different Campylobacter jejuni and Escherichia coli O157:H7
      strains to mild bactericidal treatments.

PMID- 18831277
TI  - Flavour active volatile phenols in beer.

PMID- 18831278
TI  - Host plant response of burrowing nematode resistant Musa genotypes to the root
      knot nematode, Meloidogyne incognita.

PMID- 18831279
TI  - Evaluation of the use of a decontamination step during fresh-cut leek processing
      by means of a multidisciplinary approach.

PMID- 18831280
TI  - Identification of a bacterial inhibitor of G-type lysozyme.

PMID- 18831281
TI  - Coating processes in fluidised beds: quality control model based on population
      balance theory.

PMID- 18831282
TI  - Isolation of a bacterial inhibitor of the invertebrate type lysozyme.

PMID- 18831283
TI  - High hydrostatic pressure sensitivity of virulent avian pathogenic Escherichia
      coli.

PMID- 18831284
TI  - Decontamination of apple pieces in syrup by high hydrostatic pressure.

PMID- 18831285
TI  - Plant polyphenol inhibits heat-labile enterotoxin binding in a non-specific way.

PMID- 18831286
TI  - AMF-induced bioprotection against root-knot nematodes in tomato.

PMID- 18831287
TI  - Development of a DNA macroarray for monitoring microbial population dynamics
      during sugar thick juice storage.

PMID- 18831288
TI  - Cooperative sanitation: Managing streets and gutters in late Medieval England and
      Scandinavia.

PMID- 18831289
TI  - Image and audience: Contractual representation and London's main drainage system.

PMID- 18831290
TI  - Breaking from the colonial mold: Water engineering and the failure of nation
      building in the Plain of Reeds, Vietnam.

PMID- 18831291
TI  - Turning water into power. Debates over the development of Tanzania's Rufiji River
      Basin, 1945-1985.

PMID- 18831292
TI  - Reluctant modernization. The cultural dynamics of water supply in Istanbul, 1885
      1950.

PMID- 18831293
TI  - From colonial to postcolonial irrigation technology. Technological romanticism
      and the revival of colonial water tanks in Java, Indonesia.

PMID- 18831294
TI  - Infectious disease and perioperative infections. Preface.

PMID- 18831295
TI  - Central venous catheter-associated infections.
AB  - Most patients in the hospital need vascular access: a peripheral venous line, a
      short-term non-cuffed central venous catheter (CVC), a long-term cuffed CVC, an
      implantable port or an arterial line. Such devices, although often indispensable
      and of benefit, may have the disadvantage of mechanical complications, local exit
      site infections or catheter-associated bloodstream infections (CRBSI). Apart from
      peripheral venous lines, non-cuffed CVCs are the most frequent catheter type in
      hospitals. The risk for CRBSI of such catheters is high with an incidence density
      of 2 to 7 episodes per 1000 catheter-days depending on ward-type, institution and
      geographical region. This review describes the epidemiology, the frequency and
      the risk of CRBSI among non-cuffed CVCs, provides accepted definitions as well as
      descriptions of diagnostic techniques and highlights various prevention measures.

PMID- 18831296
TI  - Sternal wound infections.
AB  - Deep sternal wound infections (DSWI) continue to be a relatively uncommon event
      occurring in about 1%-2% of all patients undergoing cardiac surgery. However, the
      sheer number of cardiac surgery patients and the relatively high mortality
      associated with DSWIs makes them of clinical relevance. This review will describe
      the current incidence of DSWIs and their associated morbidity and mortality as
      well as risk factors for the development of this complication. The microbiology
      of DSWIs will be reviewed and strategies to prevent these complications will be
      discussed with a focus on interventions that may be undertaken by the clinical
      anesthesiologist.

PMID- 18831297
TI  - Ventilator-associated pneumonia: problems with diagnosis and therapy.
AB  - The diagnosis of ventilator-associated pneumonia, VAP, is problematic because of
      a lack of objective tools that are utilized to make an assessment of bacterial
      induced lung injury in a heterogeneous group of hosts. Clinical symptoms and
      signs are used to identify patients that may have a "lung infection". However,
      the symptoms and signs can be produced by a myriad of other conditions. Recent
      clinical data also suggests bacterial-induced pathologic processes occur prior to
      the onset of the symptoms and signs. Utilizing bacterial culture alone, health
      care practitioners are forced to wait for days for results and will have to order
      days of empiric antibiotic therapy. Exploratory molecular studies utilizing clone
      libraries and molecular arrays for microbial identification document the
      inability of culture-based techniques to even identify all the microbes involved
      in VAP. These molecular studies also offer evidence that oral flora present in
      the lungs of patients with VAP, suggesting aspiration of oral secretions and/or
      biofilms on endotracheal tubes, supply the bacteria for VAP. Much more
      investigation is needed to determine the optimal timing of antibiotic treatment
      and which diagnostic molecular methods can be utilized in the ICU.

PMID- 18831298
TI  - Infectious complications of regional anesthesia.
AB  - Although individual cases have been reported in the literature, serious
      infections of the central nervous system (CNS) such as arachnoiditis, meningitis,
      and abscess following spinal or epidural anesthesia are rare. However, recent
      epidemiologic series from Europe suggest that the frequency of infectious
      complications associated with neuraxial techniques may be increasing.
      Importantly, while meningitis and epidural abscess are both complications of
      neuraxial block, the risk factors and causative organisms are disparate. For
      example, staphylococcus is the organism most commonly associated epidural
      abscess; often these infections occurred in patients with impaired immunity.
      Conversely, meningitis follows dural puncture, and is typically caused by alpha
      hemolytic streptococci, with the source of the organism the nasopharynx of the
      proceduralist. In order to reduce the risk of serious infection following
      neuraxial blockade, the clinician must be knowledgeable in the pathogenesis of
      CNS infections, patient selection, and use of meticulous aseptic technique.
      Finally, since delay in the diagnosis may result in morbidity and even death, it
      is crucial to be aware of the presenting signs and symptoms of meningitis and
      epidural abscess.

PMID- 18831299
TI  - Bioterrorism and the anaesthesiologist's perspective.
AB  - The use of non-conventional agents aimed at causing panic and terror among
      civilians has a long history. There have been uninterrupted threats and the use
      of biological and chemical weaponry from the time of early tribal conflicts to
      the Iran-Iraq war. The sole practical experience has come from the release of the
      nerve gas Sarin in a Tokyo subway (1994) and the inhalational anthrax discovered
      in Florida (2001). Drills that simulate scenarios of biological/chemical mass
      infestation have yielded valuable theoretical experience. This chapter reviews
      the main chemical and biological agents possibly obtainable by individuals and
      groups, and the anaesthesiologist's tasks during the resultant non-conventional
      multi-casualty scenarios. It briefly illustrates the chemical and biological
      pathological effects of the various intoxicants on the human body, and describes
      modes of protection and the currently available treatment, based on both military
      and civilian materials and on the authors' own experience derived from specially
      designed drills.

PMID- 18831300
TI  - Transfusion-transmissible infections and transfusion-related immunomodulation.
AB  - The risk of acquiring a transfusion-transmitted infection has declined in recent
      years. However, after human immunodeficiency virus and hepatitis B and C virus
      transmission were successfully reduced, new pathogens are threatening the safety
      of the blood supply, especially in the face of rising numbers of
      immunocompromised transfusion recipients. Despite new standards in the
      manufacture and storage of blood products, bacterial contamination still remains
      a considerable cause of transfusion-related morbidity and mortality. Better
      allograft survival in kidney transplant patients and higher cancer recurrence
      rate in surgical oncology patients after allogeneic blood transfusions
      highlighted a previously underestimated side-effect: transfusion-related
      immunomodulation (TRIM). The precise pathomechanism still remains uncertain;
      however, its mostly deleterious effects--such as a higher incidence of
      postoperative or nosocomial infections--is increasingly accepted. Although
      transfusion-related immunomodulation is thought to be mediated mainly by donor
      white blood cells, the benefit of leukoreduction on overall mortality and on
      infectious complications is highly debatable.

PMID- 18831301
TI  - Diabetes, hyperglycemia, and infections.
AB  - Postoperative infection is not only a major source of morbidity and mortality in
      patients undergoing surgery, but also an important cause of increased hospital
      stay and resource utilization. Diabetes has been shown in multiple studies to
      increase the risk of post-surgical infection. More recently, hyperglycemia has
      been investigated as an independent risk factor for postoperative infection. This
      paper will review the effects of intra-operative, postoperative, and long-term
      glycemic control on postoperative infection rates. The mechanisms by which
      surgery causes hyperglycemia will be reviewed, as well as the immunologic and
      humeral effects of hyperglycemia.

PMID- 18831302
TI  - The "six sigma approach" to the operating room environment and infection.
AB  - The patient's external environment plays a significant, and in some cases
      dominant, role in his or her infection risk. The use of ultraclean air for
      certain procedures, as well as avoidance of hypothermia have been proven to
      reduce the risk of infection. There is no data to support the routine use of
      surgical masks (by surgeons or staff), ventilating helmets, or routine cleaning
      of all environmental surfaces in between cases. More research needs to be done in
      order to determine whether OR design changes, in addition to increasing OR
      efficiency and thus reducing case times, can also reduce infection rates. Further
      research is also needed to determine whether or not double gloves and/or the use
      of antiseptic scrubbing in addition to painting are efficacious.

PMID- 18831303
TI  - Hyperoxia and infection.
AB  - Surgical wound infection remains a common and serious complication of surgery.
      Patient factors are a major determinant of wound outcome following surgery. Co
      morbidities clearly contribute, but environmental stressors as well the
      individual response to stress may be equally important. In particular, wounds are
      exquisitely sensitive to hypoxia, which is both common and preventable.
      Perioperative management can promote postoperative wound healing and resistance
      to infection. Maintaining perfusion and oxygenation of the wound is paramount.
      Once perfusion is assured, addition of increased inspired oxygen substantially
      reduces surgical site infection in at risk patients. A greater degree of
      hyperoxemia, achievable with administration of hyperbaric oxygen, is useful as an
      adjunct to the treatment of serious soft tissue and bone infections in selected
      patients. This article will review the basic science underlying these
      observations, along with the clinical data that support the use of hyperoxia in
      preventing and treating infections.

PMID- 18831304
TI  - Antibiotics and perioperative infections.
AB  - Surgical site infections remain a significant contributor to postoperative
      morbidity and mortality. It is estimated that 500,000 patients suffer from this
      complication annually. Among other interventions, appropriate administration of
      prophylactic antibiotics has been shown to decrease the risk of perioperative
      infections. The goal of prophylactic antibiotic administration is to decrease the
      risk of contamination of the wound from skin flora in the case of clean
      procedures, and to add coverage of organisms that are anticipated to contaminate
      the surgical field, as in open bowel procedures. The purpose of this review is to
      summarize the guiding principles of perioperative antibiotic administration
      including selection, timing, redosing, and discontinuation. In addition, special
      topics including likely organisms for classes of surgical procedures,
      endocarditis prophylaxis, and management strategies for patients with allergies
      will be reviewed.

PMID- 18831305
TI  - The immunocompromised adult patient and surgery.
AB  - The perioperative management of immunosuppressed patients remains relatively
      unsophisticated. Rational management involves understanding the normal immune
      response to injury as modified by the preexisting or imposed abnormalities that
      immunosuppressed patients manifest on the basis of their disease and/or
      treatment. Patients with cancer, infected with human immunodeficiency virus, and
      having had an organ transplant are extreme examples of disordered immunity and it
      is important to understand the effects of their diseases and treatments. In the
      future, however, more appropriate management will require anticipation and
      appreciation of frequent preoperative immunotherapy, a more complete
      understanding of the immunological response to anesthesia and surgery, the
      ability to assess immune reserve and stratify risk within the context of that
      profile, and a better knowledge of the immunological effect of anesthetic agents.

PMID- 18831306
TI  - The immunocompromised pediatric patient and surgery.
AB  - Surgical procedures routinely challenge the pediatric host defense mechanisms. In
      normal situations the innate and adaptive immune mechanisms are prepared for this
      challenge. However, in many circumstances these mechanisms are compromised. In
      neonates, particularly premature infants, the immune system is not fully
      developed. The etiology of the immunocompromised state in pediatric patients may
      be primary (SCID, hypogammaglobulinemia) or secondary (cystic fibrosis, sickle
      cell disease). Knowledge of the basic elements of the immune system and how these
      elements are altered in the immunocompromised patient will help guide peri
      operative management.

PMID- 18831307
TI  - Incarceration and family relationships: a call for systemic responses.

PMID- 18831308
TI  - Factorial and construct validity of the revised short form integrative
      psychotherapy alliance scales for family, couple, and individual therapy.
AB  - The Integrative Psychotherapy Alliance model brought an interpersonal and
      systemic perspective to bear on theory, research, and practice on the
      psychotherapeutic alliance. Questions have been raised about the independence of
      the theoretical factors in the model and their operationalization in the
      Individual, Couple, and Family Therapy Alliance Scales. This paper presents
      results of a confirmatory factor analysis of the scales that delineated at least
      three distinct interpersonal factors as well as shorter versions of the three
      scales to facilitate their use in research and practice. The paper also presents
      the results of a study testing each factor's association with client retention
      and progress over the first eight sessions in individual and couple therapy. At
      least two of the interpersonal factors were uniquely associated with progress in
      individual and couple functioning. Implications of the results for theory,
      research, practice, and training in individual, couple, and family therapy are
      elaborated.

PMID- 18831309
TI  - Maternal distress and women's reentry into family and community life.
AB  - This paper advances conceptualization of maternal distress following
      incarceration. We utilized a multiple case study methodology based on interviews
      with 10 mothers who demonstrated various permutations of "the triple threat"
      (depression, domestic violence, and substance abuse; Arditti & Few, 2006).
      Findings suggest that depressive symptomology persisted and worsened for mothers
      in our study and that maternal distress was indicative not only of women's
      psychological state, but also a relational and situational construct that
      embodied women's core experience. Maternal distress was largely characterized by
      health challenges, dysfunctional intimate relationships, loss related trauma,
      guilt and worry over children, and economic inadequacy. Further, maternal
      distress seemed to be intensified by the punitive traumatic context of prison and
      lessened by rehabilitation opportunities as well as support by kin and probation
      officers after reentry. Recommendations for clinicians and professionals who work
      with reentry mothers center around the need to alleviate maternal distress and
      better address women's emotional and physical health needs during incarceration
      and reentry.

PMID- 18831310
TI  - "Motherhood starts in prison": the experience of motherhood among women in
      prison.
AB  - This study aims to explore the way in which women prisoners in Israel experience
      motherhood in prison and construct their motherhood after being released. In
      depth interviews were conducted with 9 women, and the data were analyzed
      according to the phenomenological approach. The qualitative methodology generated
      5 main themes: (a) motherhood in prison as a motive for survival; (b) the sense
      of failure experienced by mothers in prison; (c) coping versus avoidance in the
      mother-child relationship during imprisonment; (d) motherhood in prison as a
      motive for change; and (e) the transition from questioning the right to be a
      mother to redeeming motherhood. The 5 themes were organized into a model that
      depicts the process of becoming a mother in prison and the move toward mending
      the experience of motherhood. The findings indicate that side by side with the
      traumatic experiences of prison are other aspects that allow for growth and
      rehabilitation. The discussion focuses on 2 main issues that evolved from the
      findings: the reasons for the change in motherhood that occurs during
      imprisonment and the aspects of prison that enable this change.

PMID- 18831311
TI  - PREP inside and out: marriage education for inmates.
AB  - Although research has demonstrated that marriage education has positive effects
      on relationship quality, little is known about how such services impact
      relationships where one partner is incarcerated. The current study implemented an
      adapted version of the Prevention and Relationship Enhancement Program (PREP
      Inside and Out) for inmates in Oklahoma correctional facilities. Inmates, with or
      without their partners, participated in the 12-hour program. The impact of the
      program was investigated on a range of relationship variables including
      satisfaction with relationship, dedication, confidence, communication skills,
      friendship, and negative interactions as reported by the inmate partner.
      Participants reported substantial gains in all variables and in overall
      satisfaction with their relationship after completing the program, regardless of
      their gender and racial/ethnic background. Implications for future marriage
      education programs and research in prisons are discussed.

PMID- 18831312
TI  - Involving caregiving grandmothers in family interventions when mothers with
      substance use problems are incarcerated.
AB  - The alarming rate of incarceration of women disproportionately affects women of
      color, frequently intersects with the women's substance use problems, and often
      results in grandmothers providing care for their grandchildren during their
      daughters' incarceration. Numerous factors complicate the grandmothers'
      caregiving experiences and contribute to strains that exceed those typically
      associated with grandparent caregiving. Such complicating factors include the
      stresses associated with their daughters' substance use problems and
      incarceration; the complex biopsychosocial needs of many of their grandchildren;
      the challenging relational issues they must address; and often, the long-term,
      multifaceted effects of poverty. Despite the critical roles they play, the
      multiple vulnerabilities they face, and the potential for multigenerational,
      culturally relevant family interventions to yield gains for all three
      generations, grandmothers have received little attention in intervention research
      with this group of families. This paper provides a theoretical and empirical
      rationale for the inclusion of caregiving grandmothers in interventions and
      research with families affected by maternal incarceration and substance use
      problems, in general, and for the promise of multifamily groups, in particular.
      Strategies for tailoring multifamily groups with this population of families are
      also included.

PMID- 18831313
TI  - Learning from the past, altering the future: a tentative theory of the effect of
      past relationships on couples who remarry.
AB  - Using grounded theory methodology 16 participants, each in a second marriage as a
      result of divorce, were interviewed individually and with their partner.
      Participants were asked to describe how their first marriages were currently
      affecting their second. Trust was the central category that emerged. From this
      central category 3 additional categories surfaced: lack of trust in the previous
      relationship, attempts to increase trust while dating, and presence of trust in
      the current relationship. Participant feedback, internal and external auditors,
      and the existing literature were all used to validate the results. A tentative
      theory, complete with provisional hypotheses, was developed that could help
      clinicians address some of the challenges described by couples who remarry.

PMID- 18831314
TI  - An exploration of lived religion in same-sex couples from Judeo-Christian
      traditions.
AB  - Religious involvement has been found to be associated with higher levels of
      commitment and relationship satisfaction among heterosexually married individuals
      (Mahoney et al., 1999). Little is known, however, about the religiosity of gay,
      lesbian, bisexual (GLB) individuals, and virtually nothing is known about
      religious involvement in same-sex couples. The purpose of this qualitative
      interview study was to examine couples' experiences of incorporating religious
      involvement into their committed relationships. In a sample of 14 same-sex
      couples, we found that couples used their spiritual/religious values to
      understand and undergird their relationships. In this process, they negotiated
      intra-couple differences in religious practices, involved themselves in
      activities that have religious or spiritual meaning to them, created religious
      social support for their relationships, and experienced some non-supportive or
      rejecting interpersonal interactions with religious family members, congregants,
      and strangers. These findings are instructive to therapists who work with same
      sex couples and the family members of GLB individuals. We conclude with specific
      suggestions for practitioners.

PMID- 18831315
TI  - How do hostile and emotionally overinvolved relatives view relationships? What
      relatives' pronoun use tells us.
AB  - Expressed emotion (EE) has been linked to negative outcomes for a variety of
      psychiatric illnesses. Despite development of effective interventions to reduce
      EE, relatively little is known about EE's antecedents or maintaining factors. The
      present study uses a novel methodology (measurement of pronouns used by relatives
      during the Camberwell Family Interview [CFI] or a problem-solving interaction
      with the patient) to explore possible cognitive correlates of EE. Participants
      were 98 outpatients with obsessive-compulsive disorder or panic disorder with
      agoraphobia and their primary relative. Results showed that relatives' pronoun
      use was stable across situations. Relatives' hostility and criticism, as measured
      by objective coding of relatives' behavior during the CFI and interactions,
      respectively, were related to relatives' decreased we-focus and increased me
      focus in the 2 situations. In contrast to expectations, relatives' emotional
      overinvolvement was related to their decreased we-focus during CFIs and
      interactions. Results support the value of using pronouns as a means to explore
      important aspects of relationship functioning.

PMID- 18831316
TI  - Introduction: Intelligentsia science inside and outside Russia.
AB  - The concept of "intelligentsia" has had a long life both as an actors' category
      and as a tool of historical analysis to understand the role of the educated elite
      in Russia and the Soviet Union. For a variety of reasons, this term has not
      achieved much prominence in exploring the assimilation of science and technology
      into Russian culture. This essay examines the term's convoluted historiography
      and makes a case for the utility of its revival--understanding "intelligentsia"
      not as a single concept or group but as a heterogeneous and evolving social
      institution. The entire volume is then introduced with these features in mind.

PMID- 18831317
TI  - The Heidelberg circle: German inflections on the professionalization of Russian
      chemistry in the 1860s.
AB  - The success of the "second importation" of science to Russia during the Great
      Reforms of the 1860s is illustrated by examining the extended postdoctoral study
      of chemists in Heidelberg. While there, they adapted the Russian intelligentsia
      institution of the "circle," or kruzhok, to cope with their alienation from the
      German culture they were confronting. Upon their return to Russia, they felt the
      lack of the communicative network they had established while abroad and
      reimported the kruzhok to serve as a central model for the formation of the
      Russian Chemical Society in 1868.

PMID- 18831318
TI  - Turning pedagogy into a science: teachers and psychologists in late imperial
      Russia (1897-1917).
AB  - The article explores the Russian teachers' tortuous campaign at the beginning of
      the twentieth century to rise above the status of "semiprofessionals" by rooting
      the legitimacy of their professional expertise, training institutions, and
      working practices in the authority of "science." This involved a radical
      reshaping of traditional pedagogy and its fusion with new, controversial
      approaches to child psychology. It also led to a proliferation of teacher
      training courses and conferences devoted to "pedagogical psychology,"
      "experimental pedagogy," and "pedology." The article analyzes how the teachers'
      professional aspirations interacted with the conflicting agendas of rival groups
      of psychologists, who were themselves engaged in bitter squabbles over the
      legitimate identity of psychology as a scientific discipline.

PMID- 18831319
TI  - The phenomenon of Soviet science.
AB  - The grand "Soviet experiment" constituted an attempt to greatly accelerate and
      even shortcut the gradual course of historical development on the assumption of
      presumed knowledge of the general laws of history. This paper discusses the parts
      of that experiment that directly concerned scientific research and, in fact,
      anticipated or helped define important global changes in the functioning of
      science as a profession and an institution during the twentieth century. The
      phenomenon of Soviet, or socialist, science is analyzed here from the comparative
      international perspective, with attention to similarities and reciprocal
      influences, rather than to the contrasts and dichotomies that have traditionally
      interested cold war-type historiography. The problem is considered at several
      levels: philosophical (Soviet thought on the relationship between science and
      society and the social construction of scientific knowledge); institutional (the
      state recognition of research as a separate profession, the rise of big science
      and scientific research institutes); demographic (science becoming a mass
      profession, with ethnic and gender diversity among scientists); and political
      (Soviet-inspired influences on the practice of science in Europe and the United
      States through the social relations of science movement of the 1930s and the
      Sputnik shock of the 1950s).

PMID- 18831320
TI  - The conquest of science: women and science in Russia, 1860-1940.
AB  - This essay describes the growing number of women in science in Russia from 1860
      to 1940, analyzing the development of a significant community in terms of three
      generations. These generations are defined by the removal of various obstacles to
      women's participation in the sciences. The decisive transitions took place with
      the creation of higher education for women in the 1870s and the establishment of
      formal gender equality by the Bolshevik regime after 1917. To develop a composite
      picture, many women's careers are examined.

PMID- 18831321
TI  - Wishful science: the persistence of T. D. Lysenko's agrobiology in the politics
      of science.
AB  - The suppression of genetics in Soviet Russia was the big scandal of twentieth
      century science. It was also a test case for the role of scientists in a liberal
      democracy. The intellectual's perennial dilemma between scientific truthfulness
      and political loyalty was sharpened by acute ideological conflicts. The central
      topic of this essay is how the conflict was played out in Soviet agricultural and
      biological science in the 1930s and 1940s. The account is focused on the role of
      the then current Soviet science policy and its basic epistemic principles, the
      "unity of theory and practice" and the "practice criterion of truth".

PMID- 18831322
TI  - Taming the primitive: Elie Metchnikov and his discovery of immune cells.
AB  - This essay argues that the idea of race had a profound, yet unacknowledged,
      impact on Elie Metchnikov's research on immunity. Making the phagocytes, the most
      primitive cells of the body, responsible for the organism's integrity, Metchnikov
      attempted to reconcile the cultural idea of primitivity as a threat with the
      notion of the body as capable of self-defense and self-organization. The vision
      of phagocytes as being both the agents of an organism's "harmony" and its
      potential enemies reflected the complications that the ideas of race and racial
      primitivity met in Russian intellectual contexts.

PMID- 18831323
TI  - AIDS: en-lighten the un-lightened.

PMID- 18831324
TI  - Search for identification, monitoring and regulation of environmental pollutants.

PMID- 18831325
TI  - Molecular markers of heavy metal toxicity--a new paradigm for health risk
      assessment.
AB  - Last decade has witnessed increased interest in studies dealing with molecular
      markers of health and disease expression of genes. Specific toxicant "signatures"
      have been detected using genome base technologies such as microarrays. Further
      toxins have been classified on the basis of these signatures. Knowledge on these
      signatures has helped in the identification of novel drug candidates. This review
      discusses the gene expression studies recently made on arsenic, cadmium, mercury,
      chromium, lead, copper, nickel, manganese, and other essential elements.
      Toxicogenomics standards and their organizations have also been briefly
      described. Although this information can not be considered as complete, recent
      reports from different laboratories on bacteria, fish, laboratory animals and
      humans have been summarized. It is expected that toxicogenomics data presented in
      this review will be helpful in planning and excretion of human health risk
      assessment programs.

PMID- 18831326
TI  - Acid rain and its ecological consequences.
AB  - Acidification of rain-water is identified as one of the most serious
      environmental problems of transboundary nature. Acid rain is mainly a mixture of
      sulphuric and nitric acids depending upon the relative quantities of oxides of
      sulphur and nitrogen emissions. Due to the interaction of these acids with other
      constituents of the atmosphere, protons are released causing increase in the soil
      acidity Lowering of soil pH mobilizes and leaches away nutrient cations and
      increases availability of toxic heavy metals. Such changes in the soil chemical
      characteristics reduce the soil fertility which ultimately causes the negative
      impact on growth and productivity of forest trees and crop plants. Acidification
      of water bodies causes large scale negative impact on aquatic organisms including
      fishes. Acidification has some indirect effects on human health also. Acid rain
      affects each and every components of ecosystem. Acid rain also damages man-made
      materials and structures. By reducing the emission of the precursors of acid rain
      and to some extent by liming, the problem of acidification of terrestrial and
      aquatic ecosystem has been reduced during last two decades.

PMID- 18831327
TI  - Root-surface phosphatase activity in shrublands across a European gradient:
      effects of warming.
AB  - Root-surface phosphatase activities were measured in natural and semi-natural
      shrublands across an European climatic gradient of temperature and rainfall
      including Wales (WL), Denmark (DK), Netherlands (NL), Hungary (HU), Italy (IT)
      and Spain (SP). In each site a warming experiment was conducted since 1999 or
      2001 by means of passive night-time warming using reflective curtains that
      covered the vegetation at night. The treatments increased yearly average soil
      temperatures around 0. 8 degrees C in most of sites. Root-surface phosphatase
      activity values ranged between 56 mg PNP g(-1) h(-1) in IT and 3.5 mg PNP g(-1)
      h(-1) in HU. Warming had no effect on root-surface phosphatase activity across
      the sites and only in Hungary a slight increase was detected. Plants at
      Mediterranean sites (IT, SP) showed a higher root-surface phosphatase activity
      than plants at temperate sites (WL, NL, DK). We suggest it might be an adaptation
      of plant species evolved under Mediterranean climate that allows them a) to
      compensate in wet period for the decrease in phosphatase activity, and thus P
      uptake, during drought periods, and/or b) to benefit from soluble organic P
      flushes following the frequent drying-rewetting episodes experienced by soils in
      Mediterranean ecosystems.

PMID- 18831328
TI  - Evaluation of adsorption potential of adsorbents: a case of uptake of cationic
      dyes.
AB  - Adsorption potential of a commercial activated carbon (FS300) has been evaluated
      for the uptake of cationic dyes namely methylene blue (MB) and rhodamine B (RB).
      Though, there are numerous studies in literature which report the sorption of MB
      (more than 40 studies) and RB (more than 10), however none of these use a common
      parameter to report the capacity of the sorbent. A protocol, based on the
      equilibrium dye concentration has been proposed to measure the sorption potential
      of a sorbent. The Langmuir model can very well describe the experimental
      equilibrium data for both dyes (coefficient of correlation > 0.999). MB (Qm =
      312.5 mg g(-1)) is more adsorbable than the RB (Qm = 144.9 mg g(-1)). Molecular
      weight and chemical structure of dye molecules seem to affect the dye uptake. The
      effect of pH on dye uptake has also been evaluated by varyingpH from 3 to 11.
      Uptake of MB increases with pH, wherein RB removal decreases with pH. Dyes could
      not be desorbed either by distilled water (0.06 and 0.11% for MB and RB
      respectively), or by 0.1 NHCl (0.136 and 3.0% for MB and RB respectively)
      indicating, chemical adsorption type of adsorbent-adsorbate interactions.

PMID- 18831329
TI  - Larvicidal activity of neem and karanja oil cakes against mosquito vectors, Culex
      quinquefasciatus (say), Aedes aegypti (L.) and Anopheles stephensi (L.).
AB  - Larvicidal effect of neem (Azadirachta indica) and karanja (Pongamia glabra) oil
      cakes (individuals and combination) was studied against mosquito species. Both
      the oil cakes showed larvicidal activity against the mosquito species tested. The
      combination of neem and karanja oil cakes in equal proportion proved to have
      better effect than the individual treatments. The combination of the two oil
      cakes recorded an LC95 of 0.93, 0.54 and 0.77% against the mosquitoes, Culex
      quinquefasciatus, Aedes aegypti and Anopheles stephensi respectively The increase
      in efficacy of the combination treatment over individuals in all the mosquito
      larvae tested was found to range about 4 to 10 fold in terms of LC50 and 2 to 6
      fold in terms of LC95.

PMID- 18831330
TI  - Do we need to examine the quantitative data obtained from toxicity studies for
      both normality and homogeneity of variance?
AB  - Most of the statistical techniques used to evaluate the data obtained from
      toxicity studies are based on the assumption that the data show a normal
      distribution and homogeneity of variance. Literature review on toxicity studies
      on laboratory animals reveals that in most of the cases homogeneity of variance
      alone is examined for the data obtained from these studies. But the data that
      show homogeneity of variance need not always show a normal distribution. In fact,
      most of the data derived from toxicity studies, including hematological and
      biochemical parameters show a non-normal distribution. On examining normality of
      data obtained from various toxicity studies using different normality tests, we
      observed that Shapiro-Wilk test is more appropriate than Kolmogorov-Smimov test,
      Lilliefors test, the normal probability paper analysis and Chi square test. But
      there are situations, especially in the long-term toxicity studies, where
      normality is not shown by one or more than one of the dosage groups. In this
      situation, we propose that the data maybe analyzed using Dunnett multiple
      comparison test after excluding the data of the groups that do not show normality
      However, the biological relevance of the excluded data has to be carefully
      scrutinized. We also observed that the tendency of the data to show a normal
      distribution seems to be related to the age of the animals. Present paper
      describes various tests commonly used to test normality and their power, and also
      emphasizes the need of subjecting the data obtained from toxicity studies to both
      normality and homogeneity tests. A flow chart suggesting the statistical
      techniques that maybe used for both the types of data showing a normal or non
      normal distribution is also proposed.

PMID- 18831331
TI  - The cholesterol lowering property of coriander seeds (Coriandrum sativum):
      mechanism of action.
AB  - Coriandrum sativum (Coriander) has been documented as a traditional treatment for
      cholesterol and diabetes patients. In the present study, coriander seeds
      incorporated into diet and the effect of the administration of coriander seeds on
      the metabolism of lipids was studied in rats, fed with high fat diet and added
      cholesterol. The seeds had a significant hypolipidemic action. In the
      experimental group of rats (tissue) the level of total cholesterol and
      triglycerides increased significantly There was significant increase in beta
      hydroxy, beta-methyl glutaryl CoA reductase and plasma lecithin cholesterol acyl
      transferase activity were noted in the experimental group. The level of low
      density lipoprotein (LDL) + very low density lipoprotein (VLDL) cholesterol
      decreased while that of high density lipoprotein (HDL) cholesterol increased in
      the experimental group compared to the control group. The increased activity of
      plasma LCAT enhanced degradation of cholesterol to fecal bile acids and neutral
      sterols appeared to account for its hypocholesterolemic effect.

PMID- 18831332
TI  - Chemosensory recognition of the marbled whiptail lizard, Aspidoscelis marmorata
      (Squamata: Teiidae) to odors of sympatric lizards (Crotophytus collaris, Coleonyx
      brevis, Eumeces obsoletus and Uta stansburiana) that represent different
      predation risks.
AB  - The ability of the whiptail lizard Aspidoscelis marmorata (Teiidae) to detect and
      discriminate chemical stimuli associated with the integument of a sympatric
      saurophagous lizard (Crotaphytus collaris) was tested. Females of A. marmorata
      were presented with cotton swabs containing chemical cues from C. collaris and
      three species of nonsaurophagous lizards, as well as water and cologne (pungency
      control), and total number of tongue-flick (TF) recorded. Other responses were
      assessed including directed TF rate, time from initial presentation of the
      stimulus to first TF (latency), time spent fleeing from the stimulus, and number
      of flight bouts. The number of TFs, directed TF rate, and number of attempts at
      fleeing exhibited by were significantly greater when females were presented with
      swabs containing cues from C. collaris as compared to nonsaurophagous lizards and
      both control treatments. A. marmorata required significantly less time to elicit
      their first TF when presented with cues from C. collaris as compared to all other
      treatments. Most previous studies have focused on the responses of lizards to
      cues associated with snake predators. This study provides the first available
      data on responses of a teiid to cues associated with a saurophagous lizard.

PMID- 18831333
TI  - Metals concentration associated with respirable particulate matter (PM10) in
      industrial area of Eastern U.P. India.
AB  - The present study deals with the assessment of ambient air quality with respect
      to respirable suspended particulate matter (RSPM or PM10 < or = 10 microm) and
      trace metals (Fe, Zn, Cu, Cr Ni, Cd, Mn and Pb) concentrations in RSPM at five
      locations of Renukoot, an industrial area of Eastern Uttar Pradesh. The 24 hr
      mean concentrations of PM10 ranged between 69.3 to 118.9 microg m(-3), which is
      well within the permissible limit (150 microg m(-3)) of national ambient air
      quality standards (NAAQS) but found higher than the prescribed annual daily limit
      of US EPA (50 microg m(-3)). The ambient air was mostly dominated by the Fe and
      least by the Cd among the metal analysed. Murdhawa, a commercial place influenced
      by vehicular population, is found to be the most polluted area of Renukoot and
      Dongia nalla (forest area) the least. The ambient air of Murdhawa is rich in Cu
      and Ni, indicating contribution of mobile sources. The Rammandir a residential
      place near the industry, is rich in Cd and Cr suggesting contribution of point
      sources. The Ni concentration is found to be alarmingly high in the air at all
      the locations except Dongia nallah, when compared with the EC (European
      Commission) limit (20 ng m(-3)). The Cd concentration is found to be higher only
      at Rammandir as compared with the EC limit (5 ng m(-3)). Mean concentrations of
      Zn, Pb and Mn are found to be almost equal in the ambient air of all the
      locations, suggesting the significance of sources contributing to presence of
      these metals. Zn, Cu, Pb and Ni having a significant correlation with PM10
      indicate the same source contributing these metals as well as PM10. The present
      study has focused on the quantitative variation in different metals in the PM10,
      which is extremely harmful due to their toxic and carcinogenic nature.

PMID- 18831334
TI  - Regulation of the expression of GA-insensitive gene homolog by light in Oryza
      sativa c.v. DongJin.
AB  - To understand the mechanism by which light regulates a gibberellin (GA)
      insensitive gene in DongJinByeo (Oryza sativa cv DongJin), both green and
      etiolated DongJinByeo seedlings were submerged in water and treated with GA.
      Total RNA from the seedlings was isolated and hybridized with cDNA of a GA
      insensitive gene homolog. The amount of transcript for the GA-insensitive gene
      homolog was higher in green seedlings than in etiolated seedlings in the absence
      of GA. However upon the addition of GA, greater accumulations of the gene
      transcript occurred in etiolated seedlings than in green seedlings. This result
      indicates the possibility that the expression of the GA-insensitive gene homolog
      transcript may be inhibited by light in the presence of GA. Light seems to
      regulate multilaterally the accumulation of the transcript of the GA-insensitive
      gene homolog in DongJinByeo (Oryza sativa cv DongJin).

PMID- 18831335
TI  - Protective effects of Peganum harmala extracts on thiourea-induced diseases in
      adult male rat.
AB  - Cancers and hepatoprotective prevention using traditional medicines have
      attracted increasing interest. The aim of our study was to characterize the
      putative protective effects of ethanol and chloroform extracts of Peganum harmala
      on thiourea-induced diseases in adult male rat. We seek to determine the effects
      of these plant extracts on body weight, thyroid and endocrine cancer parameters.
      In addition the putative hepatoprotective effect was checked by the determination
      of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities
      and the bilirubin level in the blood. Our data show that ethanol and chloroform
      extracts of Peganum harmala protected the animal against the carcinogenic effects
      induced by thiourea since neuron-specific enolase (NSE) and thyroglobulin (TG)
      levels were back to the normal range. In addition, the observed
      hepatocytotoxicity after thiourea treatment was greatly reduced (AST and ALT
      activities were respectively 270 IU/l and 60 IU/l and in the same order of
      magnitude as in the untreated rats) as well as the bilirubin levels (6
      micromol/l) especially for animals receiving the choroform preparation. Therefore
      we may suggest that extracts of Peganum harmala are efficient to reduce the
      toxicity induced by thiourea in male rat as far as the above parameters are
      concerned.

PMID- 18831336
TI  - Effect of carbon and nitrogen source amendment on synthetic dyes decolourizing
      efficiency of white-rot fungus, Phanerochaete chrysosporium.
AB  - Decolourization activity of Phanerochaete chrysosporium for three synthetic dyes
      viz., congo red, malachite green and crystal violet and impact of additional
      carbon and nitrogen supply on decolourization capacity of fungus were
      investigated. Maximum decolourizing capacity was observed up to 15 ppm. Addition
      of urea as nitrogen source and glucose as carbon source significantly enhanced
      decolourizing capacity (up to 87%) of fungus. In all the cases, both colour and
      COD were reduced more in non-sterilized treatments as compared to sterilized
      ones. Significant reductions in COD content of dye solutions (79-84%) were
      recorded by fungus supplied with additional carbon and nitrogen. A highly
      significant correlation (r = 0.78, p < 0.001) between colour and COD of dye
      solutions was recorded. Thus, a readily available carbon and nitrogen source is
      imperative to enhance the bioremediation activity of this fungus which has been
      the most suitable for synthetic dyes and textile industry wastewater treatment.

PMID- 18831337
TI  - Direct, residual and direct + residual effects of sulphur in garlic (Allium
      sativum)-maize (Zea mays) cropping sequence.
AB  - Significant positive effects of 30 kg/ha of sulphur as manifested on yield and
      yield parameters of garlic were further carried over to following maize crop.
      Garlic bulb and foliage yield (6.3 and 0.8 t/ha respectively) obtained at 30
      kg/ha of sulphur dose was significantly higher over without sulphur (3.7 and 0.5
      t/ha respectively) as revealed from two years' pooled data. Similarly number of
      leaves/plant, weight of cloves/5bulbs and weight/100 cloves at the said sulphur
      dose significantly increased over without sulphur from 10.5 to 11.9, 98.3 to
      141.2 g and from 159 to 217 g in respective manner Increase in grain yield of
      maize (residual effect) and in the economic yield of the whole cropping sequence
      (Bulb yield of garlic and grain yield of maize) i.e. direct plus residual effect
      at 30 kg/ha of sulphur dose over without sulphur was from 28.3 to 47.2 and from
      71 to 116 q/ha in respective manner i.e. with significant differences. Sulphur
      use efficiencies (kg yield/kg sulphur) of these crops at 15, 30 and 45 kg/ha over
      no sulphur were 57, 43 and 32; 53, 63 and 6 and 160, 150 and 67, all in
      respective order An optimum sulphur dose of 44.3 kg/ha produced increased bulb
      yield (over no S) worth Rs 34892 over fertilizer cost giving B:C ratio of 31.5:1.
      Utilization of sulphur added at 15, 30 and 45 kg/ha rates was 24.1, 19.3 and
      15.7% by the garlic crop; and 29.6. 24.5 and 9.02% by the following maize crop,
      thus, adding up to 54.1, 43.8 and 24.9% by the cropping sequence, all in
      respective order.

PMID- 18831338
TI  - Molecular size as a limiting characteristic for bioconcentration in fish.
AB  - The relationships between the bioconcentration factor (BCF) of chemicals in fish
      and their size, as characterized by molecular weight (MW), effective cross
      sectional diameter (Deff), and maximum diameter (Dmax) have been investigated
      using an experimental data set of 737 new and 441 existing chemicals monitored by
      the Japanese Chemical Substances Control Law (CSCL). Substances with BCF > or =
      5000 (very high bioconcentration potential) typically have MW < 550, Deff < 1.1
      nm and Dmax < 2.0 nm, respectively and the substances with BCF > or = 1000 (high
      bioconcentration potential) have MW < 550, Deff < 1.4 nm and Dmax < 2.9 nm,
      respectively Therefore, the previously suggested threshold values for Deff (0.95
      nm) and Dmax (1.5 nm) used for discriminating between bioconcentrative and non
      bioconcentrative substances were found to be somewhat small. We found that many
      substances with BCF > or = 1000 and Dmax > or = 1.5 nm have Deff < 0.95 nm.

PMID- 18831339
TI  - Glutathione and cysteine biosynthesis in two varieties of Abelmoschus esculentus
      in response to mine spoil.
AB  - The extent of accumulation of some heavy metals and glutathione and cysteine
      levels in the roots and aerial plant parts in two genotypically different
      varieties of A. esculentus (KS404 and BO2) exposed to mine spoil were
      investigated. Glutathione (GSH) level in both the varieties on control sites
      increased from basal level to 155.15 nmol g(-1) dry weight (d.wt.), almost 1.5
      fold on 30 day and attained a plateau within 60 day Mine spoil exposure of both
      the varieties decreased glutathione 1.13 fold (89.2 nmol g(-1) dry weight) during
      60 day from its basal level. GSH concentration in shoots of these varieties
      increased accompanying growth contrary to roots where it finally declined 2 fold.
      Cysteine content in control plants increased 2 fold (31.6 nmol g(-1) dry weight)
      on 30 day and finally declined 1.38 fold (22.35 nmol g(-1) dry weight, at 60
      day). Both the varieties, when exposed to mine spoil, showed enhanced cysteine
      content almost 2 fold during 30 day (50.95 nmol g(-1) dry weight) but failed to
      increase further Forshoots in both the varieties challenged with mine spoil,
      cysteine maxima reached late (15.2 nmol g(-1) dry weight, at 40 day) relative to
      control but the levels declined subsequently (11.85 nmol g(-l) dry weight).
      Contrary to GSH, cysteine content in roots of both the varieties responded
      positively to mine spoil as apparent from the 2.23 fold increase during 30 d than
      basal level although it lowered to a level of 12.85 nmol g(-1) dry weight finally
      at 60 day. Both the varieties accumulated almost maximum level of selected
      cations (Fe > Mn> Zn> Cu > Ni) during 30 day, but BO2 variety was significantly
      superior in this regard. Invariably high accumulation of such cations in roots
      over shoots indicated accumulation, retention or restricted translocation from
      root to shoot. The metal share of the edible part was just 6% of the plant load.
      Thus, present work reflects a genotypic differences in metal accumulation and
      that affected the major non-enzymatic traits or synthesis of sulthydryl compounds
      as well. The present results also indicate that metal tolerance is in part
      associated with anti-oxidant system activity.

PMID- 18831340
TI  - Effects of alcoholic extract of Momordica charantia (Linn.) whole fruit powder on
      the pancreatic islets of alloxan diabetic albino rats.
AB  - Alcoholic extract of whole fruit of Momordica charantia was prepared. Adult
      healthy albino rats were divided into four groups and received a dose of 6 mg/l00
      gm. body weight of alloxan monohydrate. Animals of group I served as diabetic
      control group. The animals of II, III, and IV groups received 25 mg, 50 mg and 75
      mg doses of the extract respectively for different durations. 75 mg dose showed
      increase in body weight. All doses of alcoholic extract of M. charantia were able
      to decrease the blood sugar level significantly. Extract feeding showed definite
      improvement in the islets of Langerhans. No toxic effect was observed in the
      liver The significant features of the study have been blood glucose once lowered
      by the treatment with M. charantia fruit extract remained static even after
      discontinuation of drug for 15 days. Blood sugar never fell below normal values
      even with a high dose, in pancreatic islets, beta cells showed definite
      improvement.

PMID- 18831341
TI  - Effect of barn ventilation on blood gas status and some physiological traits of
      dairy cows.
AB  - Twenty Holstein friesian and Brown swiss cows were used to investigate the effect
      of insufficient in barn ventilation on blood gas status and some physiological
      traits of the cows. Animals were kept in mechanically ventilated barn in stall
      barn (I); and the ventilation funnels of the barn were closed to simulate
      traditional habits of the region's breeders (II); then cows were transfered open
      shed barn (III). For each experimental of 10 days period, respiration and pulse
      rates and blood gas of animals were measured. Temperature, relative humidity, CO2
      and NH3 concentrations were recorded in each barns. In mechanically ventilated
      barn, climatic and atmospheric gas was in normal ranges for the cows but in
      unventilated barn they were at the upper levels. In experiment II, blood pH was
      decreased without pCO2 change. The highest blood pO2 and HCO3(-) levels were
      found when the animals were kept in open-shed barn (III). Measured parameters
      were not influenced by breed of the cows. Blood pH, pO2 HCO3(-), respiration and
      pulse rates of the cows were significantly affected by barn types (p < 0.05 and p
      < 0.01). Respiration and pulse rates were higher in inadequate (II) barn
      conditions than those of open-shed. Higher levels of gases, especially carbon
      dioxide, in the unventilated barn significantly influenced biological parameters
      of cows. It is concluded that poor ventilation caused considerable changes in
      physiologic parameters of the cows and can potentially affect animal health and
      production.

PMID- 18831342
TI  - Solid substrate fermentation of cassava fibrous residue for production of alpha
      amylase, lactic acid and ethanol.
AB  - There is serious concern about the disposal of solid residues left after large
      scale extraction of starch from cassava. Owing to the high starch content (55-65%
      on dry weight basis) and organic matter of these wastes, an attempt has been made
      to utilize it for the production of three bioproducts, i.e. alpha-amylase, lactic
      acid and ethanol in solid substrate fermentation by incubating the solid residue
      at different moisture holding capacity (40-80%) and incubation period (12- 60 hr
      for alpha-amylase, 24-144 hr for ethanol and 2-10 days for lactic acid). The
      highest product yield was obtained at 60% moisture holding capacity of the
      residue and period of incubation varied from 36 hr (alpha-amylase), 120 hr
      (ethanol) to 6 days (lactic acid). This study showed that the solid residues from
      cassava starch factories could serve as a low-cost substrate for bioproducts
      production.

PMID- 18831343
TI  - Multiple antibiotic resistance patterns of rhizospheric bacteria isolated from
      Phragmites australis growing in constructed wetland for distillery effluent
      treatment.
AB  - Susceptibility patterns of 12 different antibiotics were investigated against
      rhizospheric bacteria isolated from Phragmites australis from three different
      zones i.e. upper (0-5 cm), middle (5-10 cm), lower (10-15 cm) in constructed
      wetland system with and without distillery effluent. The major pollutants of
      distillery effluent were phenols, sulphide, heavy metals, and higher levels of
      biological oxygen demand (BOD), chemical oxygen demand (COD) etc. The antibiotic
      resistance properties of bacteria were correlated with the heavy metal tolerance
      (one of distillery pollutant). Twenty-two species from contaminated and seventeen
      species from non-contaminated site were tested by agar disc-diffusion method. The
      results revealed that more than 63% of total isolates were resistance towards one
      or more antibiotics tested from all the three different zones of contaminated
      sites. The multiple-drug resistance property was shown by total 8 isolates from
      effluent contaminated region out of which 3 isolates were from upper zone, 3
      isolates from middle zone and 2 isolates were from lower zone. Results indicated
      that isolates from contaminated rhizosphere were found more resistant to
      antibiotics than isolates from non-contaminated rhizosphere. Further this study
      produces evidence suggesting that tolerance to antibiotics was acquired by
      isolates for the adaptation and detoxification of all the pollutants present in
      the effluent at contaminated site. This consequently facilitated the
      phytoremediation of effluent, which emerges the tolerance and increases
      resistance to antibiotics.

PMID- 18831344
TI  - Incidence of keratinophilic fungi in waterlogged condition of paddy soil.
AB  - Prevalence of keratinophilic fungi was observed in paddy field soil during
      different stages of cultivation viz., transplanting, tillering, milking and
      maturation. Out of total 76 soil samples, 65 soil samples were found to be
      positive for the keratinophilic fungi. Fourteen species belonging to a single
      genus Chrysosporium were isolated through out the cropping season. C.
      keratinophilum (17.1%) followed by C. tropicum (13.15%) were found to be the most
      dominating geophilic species. The highest percent distribution of keratinophilic
      fungi appeared during the milking stage (100%) of paddy cultivation, followed by
      the maturation stage (89.47%).

PMID- 18831345
TI  - Diversity of root associated microorganisms of selected medicinal plants and
      influence of rhizomicroorganisms on the antimicrobial property of Coriandrum
      sativum.
AB  - The total heterotrophic bacteria, actinomycetes and fungus were enumerated from
      the rhizosphere and non-rhizosphere soil of 50 selected locally available
      medicinal plants in and around Bharathiar University. In all the plants,
      population of microorganism were higher in the rhizosphere soil than in the non
      rhizosphere soil. Among the microorganisms, bacterial population was higher in
      number followed by fungus and actinomycetes. Of the medicinal plants, the maximum
      rhizosphere effect was observed in Annona squamosa and the minimum effect was
      seen in Eclipta alba and Cassia auriculata. Among the bacteria the dominant
      species was Bacillus followed by Pseudomonas, Enterobacter, Corynebacterium,
      Micrococcus and Serratia. The Streptomyces species was found to be dominant
      followed by Deuteromycetes and Frankia among the actinomycetes. Among the fungal
      isolates Rhizopus was found to be higher in number followed by Aspergillus,
      Penicillium, Mucor and Fusarium. About 70.96% of the bacterial isolates were
      found to be nitrate reducers and 90.60% of the bacteria solubilised phosphate.
      The rhizosphere bacterial isolates were also capable of hydrolyzing starch,
      cellulose, casein, urea and gelatin. The isolates of bacteria, actinomycetes and
      fungus were also able to produce phytohormone Indole-3-acetic acid (IAA). The
      maximum IAA production was recorded by Fusarium sp (5.8 mg/l). The rhizosphere
      bacterial isolates showed resistance to 14 commercially used antibiotics. In an
      attempt to check the influence of these plant growth promoting microorganisms on
      the antimicrobial property of Coriandrum sativum against Escherichia coli MTCC
      443 and Aeromonas hydrophila MTCC-646, the results observed was not encouraging
      since the inoculants did not influence the antibacterial property. However
      extensive and in depth study is required to find out the influence of
      rhizomicroorganisms on the antibacterial property of medicinal plants. The other
      results clearly indicated that the rhizosphere microorganisms could be exploited
      for its innumerable properties and active metabolites.

PMID- 18831346
TI  - Influence of ambient ultraviolet radiation on Bufo calamita egg development in a
      semiarid zone (Catalonia, Spain).
AB  - Several experiments have shown that ambient ultraviolet-B radiation (UV-B) has
      negative effects on the development of amphibians' embryos. We studied the
      effects of UV-B radiation on development, survival and frequency of deformity
      during egg development in the Natterjack toad (Bufo calamita) from a semiarid
      region of Lleida (Catalonia, Spain). Eggs exposed to ambient levels of UV-B and
      those protected from UV-B with a filter exhibited similar developmental rate,
      mortality rate and frequency of developmental anomalies. These experiments show
      that eggs of Bufo calamita of the studied population are able to develop normally
      during embryonic period when exposed to current high levels of UV-B observed in
      Catalonia. These results will be used as reference for future studies on
      geographic variation in UV-B tolerance in this species.

PMID- 18831347
TI  - Is 'hypothesis' hypertelic in science?

PMID- 18831348
TI  - Nitric oxide-mediated pathogenesis during nicotine and alcohol consumption.
AB  - Nitric oxide (NO) is formed by different cell types in response to a variety of
      physiological and patho-physiological stimuli. The intake of nicotine and/or
      alcohol has patho-physiological effects on organ function, and the progression of
      alcohol-/tobacco-related diseases seem to be directly influenced by NO-mediated
      mechanisms. Nicotine has an adverse influence on blood vessel functionality,
      repair and maintenance. Chronic nicotine exposure augments atherosclerosis by
      enhancing the production of proinflammatory cytokines by macrophages which then
      activate atherogenic NF-kB target genes in aortic lesions. Alcohol produces NO
      which speeds up the apoptosis of neutrophils. Alcohol sensitizes the liver to
      endotoxemic shock. Nitrosative stress and increased basal levels of NO contribute
      to tumour growth. The progression of disease seems to be directed via a definite
      NO-mediated mechanism. This review gives an insight into how intake of tobacco
      and alcohol may affect quality of life.

PMID- 18831349
TI  - Effect of human chorionic gonadotropin (hCG) on expression of vascular
      endothelial growth factor a (VEGF-a) in human mid-secretory endometrial cells in
      three-dimensional primary culture.
AB  - Several lines of evidence suggest that human uterine endometrial cells can bind
      human chorionic gonadotropin (hCG) which, in turn, influences the physiology of
      implantation stage endometrium. Vascular endothelial growth factor (VEGF) appears
      to be a candidate mediator in this process. However, our knowledge about hCG
      action on VEGF in human endometrial cells is very thin. In the present study, we
      have examined microscopically hCG binding to dissociated human endometrial cells
      collected from mid-luteal phase and maintained in three-dimensional primary co
      culture on rat-tail collagen type I biomatrix and examined the effect of
      different concentrations (0, 1, 10, 100 and 1000 IU/ML) of hCG on VEGF expression
      and secretion by endometrial cells maintained in the above system. We report that
      both cytokeratin positive epithelial cells as well as vimetin positive stromal
      cells from human mid luteal phase endometrium could bind hCG and that their
      number increased (P < 0.01) steadily with time. Administration of hCG enhanced (P
      < 0.05) immunoreactive VEGF protein expression in dose dependent manner in
      endometrial cells retrieved from mid-luteal phase of cycle, and co-cultured in a
      three-dimensional cell culture system, but with no marked change in VEGF
      secretion. Collectively, it appears that hCG influences VEGF protein synthesis in
      human midluteal phase endometrial cells, but has little effect on post
      translational regulation and secretion. From physiological homeostasis point of
      view, it is likely that synthesis and secretion of VEGF exhibits a modular and
      factorial regulation to achieve a fine tuning of this potent vasotropic agent in
      receptive stage endometrium.

PMID- 18831350
TI  - Study on the diagnostic accuracy of left atrial enlargement by resting
      electrocardiography and its echocardiographic correlation.
AB  - M-mode echocardiography has been accepted as gold standard for measuring left
      atrial (LA) size. Electrocardiography (ECG) offers a simple, non-invasive, cost
      effective and reproducible method to assess LA size and it is mostly in agreement
      with echocardiography though discrepancies exist. ECGs and echocardiograms were
      obtained in 100 consecutive patients suspected of having left atrial enlargement
      due to different underlying heart diseases. The diagnostic accuracy of six ECG
      criteria of LA enlargement were evaluated comparing with LA size in M-mode echo
      study. Various criteria were found to be poor to mildly sensitive (8% to 78%) but
      highly specific (85% to 100%) for left atrial enlargement. Morris Index (PTFV1)
      was found to be the best criterion having 76% sensitivity and 92% specificity.
      Combination of criteria enhances the sensitivity at the cost of specificity.
      Overall predictive index of electrocardiogram for left atrial enlargement is not
      encouraging.

PMID- 18831351
TI  - Relationship between plasma leptin and plasma insulin levels in type-2 diabetic
      patients before and after treatment with glibenclamide and glimepiride.
AB  - Type 2 diabetes affects 100 million people throughout the world. Among the
      various factors implicated in the causation of this disease, the role of leptin,
      an obesity gene product, is increasingly being investigated. This especially
      assumes importance in the light of knowledge that obesity confers a minimum of 3
      10 fold higher risk of diabetes. This study was planned to investigate the
      relationship between leptin and insulin levels in type 2 diabetic patients before
      and after treatment with glibenclamide or glimepiride. 60 type 2 diabetic
      patients were recruited for the study and were divided into 2 groups-one
      receiving glimepiride and the other group receiving glibenclamide for duration of
      10 weeks. This study demonstrated a highly positive correlation of plasma leptin
      levels with BMI, plasma insulin and insulin resistance. No gender specific
      differences were observed in leptin concentrations. The study, however, failed to
      demonstrate any possible relationship between glycemic control as assessed by
      blood sugars/ glycosylated hemoglobin (HbAlc) and plasma leptin. The
      administration of glibenclamide or glimepiride significantly lowered blood
      glucose levels coupled with a decrease in (HbAlc). Both the drugs increased
      insulin concentrations. Glibenclamide increased leptin levels but they remained
      unaltered with glimepiride. Glibenclamide and glimepiride were found to be
      equally effective in their glucose lowering action. However, the patients
      receiving glibenclamide experienced higher episode of hypoglycaemic spells than
      those receiving glimepiride.

PMID- 18831352
TI  - Assessment of differential doses of buprenorphine for long term pharmacotherapy
      among opiate dependent subjects.
AB  - The aim of the present study was to evaluate, two different doses of sublingual
      buprenorphine (2 mg and 4 mg) among patients on maintenance treatment and to
      assess the relationship of steady state plasma level with craving. Twenty three
      male opioid dependent (ICD-10 DCR) subjects, were assigned to double blind
      randomized controlled trial of 2 and 4 mg/day doses of buprenorphine in an
      inpatient setting. They were evaluated thrice (2nd, 7th and 14th day) in 2 weeks
      for withdrawal symptoms (acute and protracted), sedation, euphoria, craving, side
      effects, global rating of well being and for measurement of plasma levels of
      buprenorphine. The data showed that there were no significant difference in
      scores of euphoria and sedation, protracted withdrawal symptoms and side effects,
      craving and overall well being and plasma level of buprenorphine among the
      subjects. However, both the groups had significant difference in score on almost
      all the measurements on final observation in comparison to initial observation.
      Both 2 mg/day and 4 mg/day dose of buprenorphine were effective in long term
      pharmacotherapy of opioid dependence without significant difference as compared
      by different measures used in the study.

PMID- 18831353
TI  - Circadian rhythm of peak expiratory flow rate in healthy north Indian men.
AB  - Peak expiratory flow rate (PEFR) variability follows a specific pattern in
      asthmatics as well as in healthy individuals. There is scarcity of data for
      Indian healthy subjects. The PEFR (L/min.) was measured with Wright's portable
      peak flow meter at 05:00, 8:00, 11:00, 14:00, 17:00, 20:00 and 23:00 hours in 42
      healthy, non-smoking adults of age group between 18-26 years. The variability of
      PEFR revealed a circadian pattern. PEFR levels tend to increase from morning at
      5:00 hours till evening at 17:00 hours, with peak PEFR in evening at 17:00 hours,
      after which there was a progressive fall in PEFR levels, till morning 5:00 hours.
      This study provides the preliminary reference data of circadian pattern of PEFR
      in healthy individuals.

PMID- 18831354
TI  - Effect of '61-points relaxation technique' on stress parameters in premenstrual
      syndrome.
AB  - Premenstrual Syndrome is a psychoneuroendocrine stress related disorder and more
      than 300 treatment modalities for PMS show that the existing remedies have not
      provided satisfactory help to relieve PMS. 61-points relaxation exercise (61-PR),
      a relatively less known hatha yoga technique, is a successful means of stress
      relaxation and is expected to relieve PMS as well. The present study was
      conducted on 50 clinically healthy women volunteers who were in their
      reproductive age group and in their premenstrual period, from which a control
      group (n = 20) and a PMS group (n = 30) based on the symptoms were identified. In
      both groups basal heart rate (HR/min), systolic (SBP; mmHg) and diastolic blood
      pressure (DBP; mmHg), electromyogram (EMG; mV), electrodermal galvanic activity
      (EDG; microv), respiratory rate (RR/min) and peripheral temperature (T; degrees
      F) were recorded and the subjects were taken through a guided 61-PR. The symptoms
      and parameters were re-recorded after the 61-PR. In control group, the basal HR
      was 82.06 +/- 8.07, SBP 111.95 +/- 8.23, DBP 76.8 +/- 6.42, EMG 4.08 +/- 2.99,
      EDG 9.77 +/- 3.29, RR 15.60 +/- 3.77 and T was 97.86 +/- 0.63. After 10 minutes
      of 61-PR, HR (77.27 +/-10.85, P < 0.05), SBP (107.35 +/- 7.41, P < 0.05), DBP
      (75.25 +/-7.57, P < 0.05), EMG (2.07 +/- 1.90, P < 0.05), EDG (8.06 +/- 2.87, P <
      0.05), RR (16.00 +/- 4.12, P < 0.05) fell significantly and T (97.97 +/- 0.64, P
      > 0.05) rose significantly. In the PMS group, the basal HR was 90.61 +/- 8.46,
      SBP 122.5 +/- 11.52, DBP 83.53 +/- 8.26, EMG 5.79 +/-2.75, EDG 13.14 +/- 6.54, RR
      19.13 +/- 3.76 and T was 93.43 -/+ 5.29. After 10 minutes of 61-PR, HR (75.58 +/-
      10.11, P < 0.0001), SBP (114.53 +/- 9.70, p < 0.0001), DBP (77.46 +/- 8.68, P <
      0.0001), EMG (2.56 +/- 1.77, P < 0.0001), EDG (10.64 +/- 5.72, P < 0.0001), and
      RR (16.13 +/- 3.76, P < 0.0001) declined to a much greater extent and T (93.49 +/
      5.28, P < 0.0001) rose more significantly. These results suggest a reduction in
      sympathetic activity by 61-PR, also the high basal sympathetic tone present in
      subjects of PMS group due to stress is considerably reduced by relaxation. 61-PR
      is effective in providing relief from PMS and may be a useful adjuvant to medical
      therapy of PMS and other stress disorders.

PMID- 18831355
TI  - Oculohypotensive effects of foeniculum vulgare in experimental models of
      glaucoma.
AB  - PURPOSE: Evaluation of oculohypotensive activity of single drop application of
      aqueous extract of Foeniculum vulgare in experimental models of glaucoma.
      METHODS: The evaluation of oculohypotensive activity of Foeniculum vulgare was
      done in rabbits with normal intraocular pressure (IOP) and with experimentally
      elevated IOP. The experimental increase in IOP was achieved using water loading
      and steroid induced glaucoma models. RESULTS: The aqueous seed extract of
      Foeniculum vulgare exhibited 17.49, 21.16 and 22.03% reduction of intraocular
      pressure (IOP) in normotensive rabbits at 0.3%, 0.6% and 1.2% (w/v)
      concentrations respectively. The 0.6% concentration was further evaluated in
      acute and chronic models of glaucoma. A maximum mean difference of 31.20% was
      observed between vehicle treated and extract treated eyes in water loading model
      while a maximum mean IOP lowering of 31.29% was observed in steroid induced model
      of glaucoma. CONCLUSIONS: The aqueous extract of Foeniculum vulgare possesses
      significant oculohypotensive activity, which was found to be comparable to that
      of timolol. Further investigations into the mechanism of action, possible
      toxicity and human clinical trials are warranted before the Foeniculum vulgare
      finds place in the arsenal of antiglaucoma drugs prescribed by physicians.

PMID- 18831356
TI  - Arsenic induced toxicity on testicular tissue of mice.
AB  - Effect of arsenic was studied on the testicular tissue of Swiss albino mice.
      Sodium-meta-arsenite (NaAsO2) was administered to adult mice (25 +/- 30 g) at a
      dose level of 30 mg/L and 40 mg/L through drinking water for 30, 45 and 60 days.
      After the treatment, the testicular organ was removed, weighed and processed for
      histopathological observation. No change in the body weight was recorded in
      treated groups after arsenic exposure but significant decrease in the relative
      testicular weight was observed in comparison with the control. The result showed
      that arsenic-treated mice exhibited dose dependent gradual reductions in
      seminiferous tubular diameter and various gametogenic cell population i.e.
      resting spermatocyte, pachytene spermatocyte and step-7-spermatid except
      spermatogonia. Leydig cell atrophy was significantly increased in dose dependent
      manner indicating a definite effect of arsenic on the spermatogenesis in mice.
      These observations were supported by gradual reduction in Leydig cell population
      in the above treated groups. In conclusion, the above results confirm the toxic
      effect of arsenic in testis of mice.

PMID- 18831357
TI  - Modulation of pain perception by ramipril and losartan in human volunteers.
AB  - The angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor
      blockers (ARBs) are a well known entity and have been used in therapeutics for
      various indications like hypertension, myocardial infarction and CHF. However,
      there is a renewed interest in these compounds in terms of their effects on pain
      perception in animals as well as in human beings. They have yielded contradictory
      results, showing hyperalgesia in some studies but analgesia in others. Hence this
      study was undertaken to evaluate the effect of Ramipril (an ACE-I) and Losartan
      (an ARB) on pain perception in human volunteers using cola caps and handcuff of
      sphygmomanometer. A total of 30 healthy, normotensive individuals with no
      previous history of intake of analgesics during or 4 weeks prior to the study
      were selected after an informed consent. The first group received a single dose
      of placebo, the second group received Ramipril (2.5 mg) & the third group
      received Losartan (50 mg). Pain perception threshold (the point at which an
      individual first experiences pain) and the maximum tolerated pain were assessed
      using the above method. The control group showed no significant changes in pain
      threshold, but the group receiving either Ramipril or Losartan showed a decline
      in threshold for maximum tolerated pain. Only Ramipril and not Losartan decreased
      the pain perception threshold. Our study revealed that single dose treatment of
      healthy volunteers with Ramipril and Losartan may cause algesia as early as after
      ingestion of the first dose and further studies are needed to study their long
      term effects on pain perception.

PMID- 18831358
TI  - Chloroquine should be used with care in mental health disorders.

PMID- 18831359
TI  - Chloroquine's patho-toxicological effect on the retina--a nitric oxide and camp
      mediated mechanism.

PMID- 18831360
TI  - "Global environmental problems".

PMID- 18831361
TI  - Combined effects of heavy metal (Hg) concentration and algal (Chlorella vulgaris)
      food density on the population growth of Brachionus calyciflorus (Rotifera:
      Brachionidae).
AB  - The combined effects of two food levels (0.5 x 10(6) and 1.5 x 10(6) cells ml(-1)
      of Chlorella vulgaris) and five concentrations (0, 0.000625, 0.00125, 0.0025,
      0.005 mg l(-1) of HgCl2) of mercury on the population growth of the rotifer
      Brachionus calyciflorus was evaluated. The growth experiments were conducted for
      18 days at 23+/-1 degrees C under continuous fluorescent illumination. For each
      food level - heavy metal combination, we maintained 3 replicates. Our data showed
      that regardless of food level, increase in the heavy metal concentration in the
      medium resulted in decreased population growth of B. calyciflorus. At any given
      heavy metal concentration, B. calyciflorus grown under higher food levels had
      higher population abundance. The rate of population increase was significantly
      influenced by both the heavy metal concentration and the algal level. The highest
      population growth rate (0.435+/-0.003 per day) was observed in controls at 1.5 x
      10(6) cells ml(-1). The results of this study were discussed in relation to the
      protective role of algal density against heavy metal toxicity.

PMID- 18831362
TI  - Biomanagement of sago-sludge using an earthworm, Eudrilus eugeniae.
AB  - Sago, the tapioca starch is manufactured by over 800 small-scale units located in
      the Salem district, Tamil Nadu, India. During the processing of sago it generates
      huge quantities of biodegradable solid waste, as crushed tubers. In present study
      an attempt was made to convert these biodegradable solid sago tubers into value
      added compost using an exotic earthworm, Eudrilus eugeniae. The experiments were
      carried out in a plastic tray at various concentrations of sago-sludge (50% 75%
      and 100%) for a period of 90 days. During the vermicomposting, data were
      collected on life form (cocoon, non clitellates, clitellates) of earthworm and it
      was found to be high in 50% followed by 75% and 100% concentrations. Chemical
      analysis of worked substrates showed a step wise increase of nitrogen and
      phosphorus. The fold increase of phosphorus and nitrogen were found to be high
      for sago-sludge undergoing vermicomposting than the control. During the
      composting period the organic carbon decreased from its initial value of 58, 76
      and 107 mg/kg to 21, 24 and 65 mg/kg for 50, 70 and 100%, respectively The
      microbial analysis showed that after 75 days of composting, their population
      stabilized and further increase in composting period did not increase their
      population size. The results indicate that 50% and 75% concentration of sludge
      mixed with bedding material was ideal for the vermicomposting.

PMID- 18831363
TI  - Impact of different doses of lead on internal organs of quails.
AB  - Lead (Pb) is the most ancient poison known to man. In the present study, amount
      of accumulation of Pb in liver, kidney, ovary and testes of rain quail was
      studied using different doses of lead. Spectrophotometric analysis of heavy metal
      treated organs was carried out to determine the amount of metal accumulation in
      these organs. LD50 value was 4 ppm. Dose of lead was given in three ranges of
      low, medium and high. It was observed that testes (< or =6.8 x 10(-6)) mgkg(
      1)day(-1) and ovary (< or =7.5 x 10(-6)) mgkg(-1)day(-1), accumulated low amount
      from different doses when given continuously for 21 days. In contrast to this,
      liver (< or =9.2 x 10(-6)) mgkg(-1)day(-1) and kidney (< or =9.3 x 10(-6)) mgkg(
      1)day(-1) accumulated the maximum amount of metal when treated for the same
      number of days. This study is quite unique and astonishing as the period for
      intoxication is short (21 days) as compared to the long ones (91 days and above).
      Our results show that generally metal accumulation is highest in liver, while it
      is low in gonad.

PMID- 18831364
TI  - Seasonal activity of Bombus terrestris L. in east Mediterranean region, Turkey.
AB  - Bumblebees have economical importance in most of wild and cultivated plants. They
      can be abundant in suitable habitats and have a broad flower choice. Bombus
      terrestris was collected at intervals during 2002 and 2003 from various flora and
      ecosystems of east Mediterranean region of Turkey. In this study, plants visited
      by Bombus terrestris, seasonal activities, distribution and altitudes were
      determined. Bombus terrestris have boon seen throughout Turkey in a wide range of
      habitats from sea level to 1560 m altitude within all the major native vegetation
      types. Prevalence of queens, workers and males of Bombus terrestris differed due
      to altitude. More frequently observed at 0-600 m, declining above 600 m in
      relation to general climate requirements.

PMID- 18831365
TI  - Chromium (VI) tolerance in two halotolerant strains of Nostoc.
AB  - The present study reports on chromium (VI) tolerance of two cyanobacterial
      strains Nostoc linckia and Nostoc spongiaeforme isolated from salt affected soils
      using uni-algal and bi-algal systems. Besides distinct halophilism, the two
      strains exhibited remarkable tolerance to chromium (VI) and revealed 1.2 to 2.8
      times more chlorophyll in the presence of the metal. While phycobilins and
      carotenoids also increased in Nostoc linckia with total dissolved salts (TDS) as
      well as metal, a decline was observed in Nostoc spongiaeforme in the presence of
      Cr (VI). Relative algal biomass (as % of control) showed significantly higher
      values (123-239) in Nostoc linckia in the presence of salt, metal and combination
      of the two. In Nostoc spongiaeforme it declined in the presence of metal (72-81)
      but increased in the presence of salts (143-249) and also in the binary systems
      (121-440). The bi-algal consortium showed relatively less tolerance to salt and
      metal stress. Nostoc linckia (20 day culture) showed upto 40% chromium removal
      whereas Nostoc spongiaeforme showed up to 12% removal, indicating greater
      suitability of the former for use in bioremediation studies.

PMID- 18831366
TI  - Assessment of bio-medical waste management in three apex government hospitals of
      Agra.
AB  - Waste management practices in three apex government hospitals of Agra viz.,
      Sarojini Naidu Medical College, Lady Lyall Maternity Hospital and District
      Hospital were studied during January 2004-January 2005. Data were collected with
      the help of (i) personal observations of the waste treatment and disposal
      practices and (ii) assessment of knowledge, attitude and practices of working
      personnel with the help of questionnaires. The results obtained indicated lack of
      knowledge and awareness regarding legislations on bio-medical waste management
      even among qualified hospital personnel. None of these hospitals were equipped
      with higher technological options e.g. incinerator autoclave, microwave and had
      no facilities to treat the liquid waste generated inside the hospital. It is
      concluded that generation and implementation of a waste management policy
      institutiona/organizational set up, training and motivation must be given
      paramount importance to meet the current needs and standards of bio-medical waste
      management in these hospitals.

PMID- 18831367
TI  - Reproduction and growth of the freshwater prawn, Palaemon paucidens (Decapoda:
      Palaemonidae) in a lake of Korea.
AB  - This study analyzed the reproduction and growth of freshwater prawn, Palaemon
      paucidens De Haan 1844 from Suk-dang lake(Korea). The analysis of the sex ratio
      showed a higher proportion of males than that of females. The average size of the
      eggs was 6.12 (+/-0.55) mm3 in the non-eyed stage (stageA) and 7.20 (+/-0.86)mm3
      in the eyed stage (stage B). The reproductive output (RO) calculated with the
      dried-body weight of an incubating female and the weight of the eggs in dried
      condition was 26.97% (n = 17) of the average females weight. Incubating prawn
      appeared in April, and the gonadosomatic indices(GSI) showed the highest value
      during three months from January to March. Based on the month when there was a
      high proportion of incubating females with a high GSI, the estimated spawning
      season of P. paucidens was April. The maturity of the female was evaluated by the
      development of the ovaries and the existence of eggs. The average body length
      when 50% of the females in the group reached maturity was 8.55 (+/-2.74) mm. The
      analysis of the length-frequency distribution showed that the life span of P.
      paucidens ranged from 12 to 13 months. Females mature faster than males.

PMID- 18831368
TI  - Ovarian development in Labeo dyocheilus (McClelland) during active reproductive
      phase under captive and wild conditions.
AB  - Ovarian development in Labeo dyocheilus was assessed during active reproductive
      phase under ambient environmental conditions in captivity and wild. Increasing
      day length and water temperature seemed favourable for ovarian development in
      female L. dyocheilus under both conditions. Gonadosomatic index (GSI) was lower
      in May and higher in July in captivity (6.168 and 13.366) and wild (5.798 and
      16.166) respectively Ovarian development started little bit in advance in
      captivity with late yolk vesicle stage oocyte in May when yolk globule stage
      oocytes were prominent in wild. Fully grown oocytes with germinal vesicle
      migration (GVM) and germinal vesicle breakdown (GVBD) stages were observed in
      July in both conditions. Degree of transformation of developing oogonials into
      advance stage oocytes was observed to be better in wild fish compared to
      captivity reared ones. The histophysiological changes in liver corresponded well
      to the progression of ovarian development. Successive granulation and
      vacuolization of hepatocyte cytoplasm were indicative of augmented synthetic
      activity and probably mobilization of energy content for oocyte growth. These
      observations indicated that normal ovarian development of L. dyocheilus under
      captivity in Tarai region of Uttarakhand would be useful for success of its seed
      production in captivity for stock augmentation in wild or species diversification
      in aquaculture.

PMID- 18831369
TI  - Effect of 2,4-dichlorophenoxyacetic acid on growth, protein and chlorophyll-a
      content of Chlorella vulgaris and Spirulina platensis cells.
AB  - In this study, effect of different 2,4 -dichlorophenoxyacetic acid (2,4-D)
      concentrations (0.0, 9.10(-5), 9.10(-4), 9.10(-3) and 9.10(-2) mM) on growth
      rate, content of protein and chlorophyll-a in Chlorella vulgaris and Spirulina
      platensis cells was investigated. The most stimulatory effect on growth rate,
      protein and pigment ratio of C. vulgaris and S. platensis was observed at 9.10(
      4) mM concentrations of 2,4-D. The results show that low concentrations of 2,4-D
      have hormonal effect due to being a synthetic auxin. Cell number protein and
      pigment rates were inhibited at 9.10(-2) mM concentration in C. vulgaris. Such
      parameters were inhibited in S. platensis, both at 9.10(-3) and 9.10(-2) mM 2,4-D
      concentrations. This is due to herbicidal effect of high concentrations of 2,4-D.
      S. platensis was found to be more sensitive than S. vulgaris to 2,4-D
      applications. The use of algae as bio-indicators in herbicide contaminated fresh
      water habitats, was discussed.

PMID- 18831370
TI  - Environmental impact reduction through ecological planning at Bahia Magdalena,
      Mexico.
AB  - For analyzing basic marine and coastal characteristics we selected the potential
      sites where shrimp culture could be developed in a large coastal zone, Bahia
      Magdalena, Baja California Sur, Mexico. Based on our analysis, 6 sites were
      preselected and field stages of work were then developed to assess the precise
      suitability of each site in order to develop the proposed aquaculture activities.
      In ranking the suitability we were able to recommend the most appropriate places
      to develop shrimp culture in this region. Also, knowing the exact biological,
      physico-chemical and social environment, we determined the best species to
      cultivate, the recommended total area and the methodology to be used to lessen
      the environmental impact and to obtain the maximum profitability Our methodology
      could be used not only to select appropriate sites for shrimp culture in other
      coastal lagoons, but it also could be applied to assess the suitability in a
      quick and accurate way, of any other production activity in coastal zones.

PMID- 18831371
TI  - Influence of endosulfan and monocrotophos exposure on the activity of NADPH
      cytochrome C reductase (NCCR) of Labeo rohita (Ham).
AB  - The response of NADPH cytochrome C reductase (NCCR) activity in liver of Labeo
      rohita fish exposed to the pesticides, 0.25 microgl(-1) endosulfan and 2 mg/l
      monocrotophos was studied. In terms of specific enzyme activity (mU/mg protein) a
      significant level of NCCR was observed in the liver tissues of Labeo rohita
      exposed to the pesticides, when compared to the control fish (2.460 mU/mg
      protein). Increase of NCCR activity was more in the liver of the fish exposed to
      monocrotophos (4.595 mU/mg protein) than those exposed to endosulfan (2.850 mU/mg
      protein). The results demonstrate that the pesticides, endosulfan and
      monocrotophos, interfere with NADPH dependent monoxygenase mechanism and are
      effective inducers of NADPH cytochrome C reductase. The activity of NCCR in the
      liver tissue of Labeo rohita may serve as a useful tool for monitoring aquatic
      pollution.

PMID- 18831372
TI  - Devicyprin induced gonadal impairment in a freshwater food fish, Channa punctatus
      (Bloch).
AB  - Synthetic pyrethroids are the recent major class of broad spectrum, photostable,
      organic insecticides used in agricultural, domestic and veterinary applications
      and now account for more than 30% of global insecticide use. Cypermethrin is
      metabolized and eliminated significantly more slowly by fish than by mammals or
      birds, which may explain this compound's high toxicity in fish compared to other
      organisms. The present communication deals with histoanatomical alterations in
      the gonads of a local fresh water food fish, Channa punctatus exposed to 0.033
      ppm (96 hr LC50 X 1/10) concentration of a synthetic pyrethroid, devicyprin
      (cypermethrin 25%) in aquatic medium of aged tap water for 15, 30 and 45 days
      respectively. In testis, exposure dependent histological damage has been observed
      in terms of vacuolization, condensation of spermatogonic cells, distortion of
      tubular epithelium, shrinkage of interstitial cells and general inflammatory
      responses. Longest exposure of 45 days has resulted in peculiar starry-sky
      appearance of the testicular tissue. Gross histo-anatomy of ovarian tissue
      reveals epithelial lesions, inflammatory responses, stromal hemorrhage, increased
      interstitium and shrinkage of yolk vesicles towards periphery These findings are
      quite suggestive of reproductive impairments leading to delayed gonadal maturity
      and adversely affecting processes of sperm production and ovulation and thus, the
      fish production.

PMID- 18831373
TI  - Seed germination of Cistus creticus L. and Cistus laurifolius L. as influenced by
      dry-heat, soaking in distilled water and gibberellic acid.
AB  - The effects of dry-heat and seed soaking in distilled water or in gibberellic
      acid on germination performance of Cistus creticus L. and C. laurifolius L. were
      studied in the present study Germination percentages of two Cistus species were
      low due to dormancy Soaking in distilled water for 24 hr resulted in 28%
      germination in C. creticus and 43% in C. laurifolius. Gibberellic acid
      applications (20, 100 and 250 mg l(-1)) for 24 hr gave 32, 30 and 23%
      germination, respectively in Cistus creticus and 33, 37 and 28% germination,
      respectively in C. laurifolius. Dry-heat pretreatments at 50, 80 and 100 degrees
      C for several times (1-60 min) also significantly increased germination
      percentage in two species. The highest germination in C. creticus was obtained
      with dry-heat at 100 degrees C for 1 or 5 min (80% and 83%, respectively) and in
      C. laurifolius at 100 degrees C for 5 min (87%). A significant increase in
      germination rate was also achieved under different pretreatments. The
      physiological dormancy caused by an impermeable seed coat can be overcome by dry
      heat pretreatments in two Cistus species.

PMID- 18831374
TI  - Accumulation, tolerance and impact of aluminium, copper and zinc on growth and
      nitrate reductase activity of Ceratophyllum demersum (Hornwort).
AB  - Ceratophyllum demersum (homwort) was subjected to toxic concentrations of Al (3
      and 9 mg l(-1)), Zn (3 and 9 mg l(-1)) and Cu (2.5 and 7 mg l(-1)) in culture
      solutions for 15 days. The higher dose of Al enhanced the chlorophyll content
      significantly (p<0.05) in the first 6 days of treatment while other treatments
      caused marked reductions. Nitrate reductase activity (NRA) was significantly
      reduced (p<0.05) byAl, Cu and Zn toxicity and ceased completely in plants treated
      with Cu by the 6th day of treatment. Dry biomass and relative growth rate were
      reduced significantly (p<0.05) by metal treatment. Tolerance index of the plant
      was low for Cu (21.62 and 13.43% at low and high doses, respectively) and
      moderate for Zn (63.74 and 54.85%) and Al (72.83 and 68.79%). Accumulation ofAl,
      Zn and Cu was threefold at higher doses compared with the lower doses but the
      bioconcentration factors (BCF) were very low indicating that this plant is not a
      hyper accumulator of these metals.

PMID- 18831375
TI  - Histoenzymological study on the toxicity of copper sulphate in the digestive
      glands of Lymnaea luteola.
AB  - During 24 and 48 hr of exposure, the digestive glands of Lymnaea treated with a
      lethal concentration of 0.038 mgl(-1) CuSO4 revealed intense activity of acid
      phosphatase in perilobular margin. On the other hand, same area of the gland
      showed moderate activity of ATPase during 24 and 48 hr of exposure. However,
      alkaline phosphatase showed average activity in perialveolar region and
      perilobular margin during 24 and 48, and 72 hr of exposure respectively The
      changes in the activity of these enzymes were nonsignificant in alveolar margin
      and perialveolar region of the gland. It is interesting to note moderate activity
      of acid phosphatase in perialveolar region during 24 hr of exposure.

PMID- 18831376
TI  - Evaluation of physical, chemical and microbiological properties of lake Uluabat,
      Turkey.
AB  - Lake Uluabat, known for its scenic beauty and richness of aquatic life, is
      situated in Marmara Region, Bursa (Turkey). On account of its importance, lake
      Uluabat was designated by the Ministry of Environment as a Ramsar site in 1998.
      Physical, chemical and microbiological parameters of the aquatic ecosystem in
      lake Uluabat were measured monthly at five stations from February 2003 to January
      2004. The results showed that lake Uluabat can be classified as Class I with
      respect to temperature (16.36 +/- 7.47 degrees C), nitrate nitrogen (0.63 +/-
      0.50 mgl(-1)), sodium (9.64 +/- 2.78 mgl(-1)), chloride (20.45 +/- 4.59 mgl(-1)),
      sulphate (54.80 +/- 29.97 mgl(-1)); as Class II with respect to dissolved oxygen
      (7.62 +/- 1.99 mgl(-1)), ammonium nitrogen (0.52 +/- 0.49 mgl(-1)), chemical
      oxygen demand (35.74 +/- 10.66 mgl(-1)), total coliform (2027 MPN100 ml(-1)
      (average value)); as Class III with respect to pH (8.69 +/- 0.16) and as Class IV
      with respect to total nitrogen (84.94 +/- 66.13 mgl(-1)), total phosphorus (1.11
      +/- 3.01 mgl(-1)), biochemical oxygen demand (21.21 +/- 6.60 mgl(-1)) according
      to TWPCR (Turkey Water Pollution Control Regulation). The nutrient content of
      lake waterapparently indicated that lake had an eutrophic characteristic.
      Phosphorus was determined as a limiting factor in lake. The measured hardness
      values (140.94 +/- 14.61 CaCO3 mgl(-1)) indicated that lake water was classified
      as soft/hard during the study period. Eutrophic characteristic of the lake and
      contaminant accumulation in water will probably affect the future use of the
      lake. Therefore, pollution parameters must be regularly monitored and evaluated
      according to aquatic living and local regulations.

PMID- 18831377
TI  - Soil mycofloral responses following the exposure to 2, 4-D.
AB  - 2, 4-dichlorophenoxyacetic acid (2,4-D) is a post emergence herbicide. The tests
      were conducted to study the toxicity of 2,4-D using EC50 value in four dilutions.
      2,4-D was applied at concentration of 25, 50, 75, 100, 200 and 300 mg l(-1) in
      the potato Dextrose agar medium. The effect of this herbicide was evaluated as
      the colony forming unit (CFU). EC50 value for 10(-3) dilution of soil was 138 +/-
      5.944 mg l(-1). Soil physico-chemical parameters and mycofloral properties were
      also evaluated. Qualitatively 10 genera of fungi were observed in untreated soil,
      whereas 4 genera were found in 2,4-D administered dose.

PMID- 18831378
TI  - Physico-chemical and microbial characteristics of the coral reef environment of
      the Gulf of Mannar marine biosphere reserve, India.
AB  - Investigation on physico-chemical parameters and bacteial characteristics of the
      coral reef environs of the Gulf of Mannar biosphere reserve was studied. The
      study found the influence of different physico-chemical parameters on one another
      and also on the distribution of the total heterotrophic bacteria (THB) in the
      coral reef areas. Nutrients exhibited considerable seasonal and spatial
      variations with influence on the bacterial population. Coral reef areas recorded
      higher bacterial population density both in water (3.5 to 18 x 10(5) CFU ml(-1))
      and sediment (1 to 14 x 10(7) CFU g(-1)) samples than the non coral reef areas
      (3.4 to 10.5 x 10(4) CFU ml(-1) in water and 0.9 to 7 x 10(6) CFU g(-1)). The
      study also found the dominance of gram negative groups at all the three stations
      (64.73, 63,5 and 72.59%) with Pseudomonas contributing maximum number of strains
      in all the samples. In addition Vibrio, Aeromonas, Flavobacterium, Cytophaga,
      Enterobacter and Alcaligenes were also recorded. The gram positive group was
      represented by Bacillus, Micrococcus, Arthrobacter and Corynebacterium. The
      genetic composition of THB isolated from the coral mucus revealed the presence of
      Vibrio and Micrococcus in all the coral mucus.

PMID- 18831379
TI  - Defoliation levels of oriental spruce by Ips typographus (L.) in relation to
      elevation and exposure.
AB  - A study concerning the effects of elevation and exposure of the spruce forests on
      defoliation levels of oriental spruce (Picea orientalis (L.) Link.) by Ips
      typographus L. was carried out during 2005 and 2006 in Artvin-Hatila National
      Park, Turkey Nine spruce stands were selected at 3 zones of elevations (1000-1350
      m, 1350-1700 m and 1700-2000 m) and at different aspects to assess the role of
      elevation and exposure in the crown defoliation level and body length of beetles.
      Influence of bark thickness and trunk diameter at 1.3 m on the damage caused by
      the pest was investigated as well. The results of the study were as follows: (1)
      The mean defoliation level was highest at 1700-2000 m following by 1350-1700 m
      and 1000-1350 m. (2) The highest defoliation levels occurred on southern slopes
      following by eastern and northern slopes at 1700-2000 m. (3) No statistical
      differences were found in the mean bark thickness between tree defoliation levels
      1, 2, 3 and 4. (4) Mean trunk diameters of dead trees (level 4) were
      significantly greater than those with defoliation levels 0, 1 and 2. (5) Mean
      body length of I. typographus at upper zones was significantly higher than those
      at middle and lower zones.

PMID- 18831380
TI  - Removal of fluoride by thermally activated carbon prepared from neem (Azadirachta
      indica) and kikar (Acacia arabica) leaves.
AB  - The present investigation deals with fluoride removal from aqueous solution by
      thermally activated neem (Azadirachta indica) leaves carbon (ANC) and thermally
      activated kikar (Acacia arabica) leaves carbon (AKC) adsorbents. In this study
      neem leaves carbon and kikar leaves carbon prepared by heating the leaves at 400
      degrees C in electric furnace was found to be useful for the removal of fluoride.
      The adsorbents of 0.3 mm and 1.0 mm sizes of neem and kikar leaves carbon was
      prepared by standard sieve. Batch experiments done to see the fluoride removal
      properties from synthetic solution of 5 ppm to study the influence of pH,
      adsorbent dose and contact time on adsorption efficiency The optimum pH was found
      to be 6 for both adsorbents. The optimum dose was found to be 0.5g/100 ml forANC
      (activated neem leaves carbon) and 0.7g/100 ml forAKC (activated kikar leaves
      carbon). The optimum time was found to be one hour for both the adsorbent. It was
      also found that adsorbent size of 0.3 mm was more efficient than the 1.0 mm size.
      The adsorption process obeyed Freundlich adsorption isotherm. The straight line
      of log (qe-q) vs time at ambient temperature indicated the validity of langergren
      equation consequently first order nature of the process involved in the present
      study. Results indicate that besides intraparticle diffusion there maybe other
      processes controlling the rate which may be operating simultaneously. All
      optimized conditions were applied for removal of fluoride from four natural water
      samples.

PMID- 18831381
TI  - Phytoplankton as index of water quality with reference to industrial pollution.
AB  - In this paper Shannon-Weaver (SI-3.58-4.07, SII-3.1-3.72, SIII-1.64-2.25, SIV
      2.54-2.95 and SV-3.09-3.23) diversity index was applied to surface phytoplankton
      to study the water quality status of river Bhadra receiving Mysore paper mill and
      Iron and steel mill effluent. A total of 45 species of phytoplankton belonging to
      5 classes were recorded and study indicated that the phytoplankton diversity
      (Chlorophyceae-19 species, Bacillanophyceae-16 species, Cyanophyceae-07 species,
      Euglenophyceae-2 species and Chrysophyceae-1 species) did not reveal the same
      type of water quality (water temperature 24.62-27.32 degrees C, pH-7.08-7.25,
      electrical conductivity-67.49-201.94 micromhos/cm, dissolved oxygen-4.13-5.98
      mgl(-1), chloride-12.30-40.85 mgl(-1), calcium-6.49-23.74 mgl(-1), total hardness
      28.98-76.65 mgl(1), magnesium-4.69-15.92 mgl(-1), total alkalinity-77.26-86.53
      mgl(-1), BOD-1.88-4.01 mgl(-1), COD - 16.53-45 mgl(-1), phosphate-0.001-0.53 mgl(
      1), sodium-2.70-7.46 mgl(-1) and potassium-2.37-7.88 mgl(-1)). The investigation
      emphasized the need of phytoplankton community as index of water quality polluted
      by industrial effluents at the downstream stretch of the Bhadra river.

PMID- 18831382
TI  - Solubilization of water-insoluble beta-glucan isolated from Ganoderma lucidum.
AB  - The fungal beta-D-glucan is a biological response modifier (BRM), but a major
      obstacle to the clinical utilization of beta-glucan BRMs is thei relative lack of
      solubility in aqueous media. Water insoluble fungal glucans extracted by alkali
      from the mycelia of Ganoderma lucidum were sulfated to yield their corresponding
      water-soluble derivatives. Insoluble glucan is dissolved in methyl sulfoxide and
      urea, and is partially sulfated with sulfuric acid. The sulfated glucan (SGL)
      yield prepared from insoluble glucan (IGL) was 85%, the sulfation degree of SGL
      was about 14.9%, and the solubility of SGL was above 95% in water. The monosugar
      SGL content was 34.9% alpha-glucose and 35.9% beta-glucose. The mean molecular
      weight (MW) of SGL was shown as a single peak on Sepharose CL-4B column
      chromatography, and their MW was approximately 9.3 kDa. The 13C NMR spectrum
      analysis shows that SGL has a high similarity with the beta-(1-->3)-linked triple
      helical control.

PMID- 18831383
TI  - Allelotoxicity of Parthenium leaf extracts on cytomorphological behaviour of
      sunflower (Helianthus annuus).
AB  - In recent decades allelopathy has gained much attention in the sustainable
      agricultural systems. It is necessary to trace out the mechanism of action of
      allelochemicals of plants on other plants. Allelochemicals of different plants
      interact differently with each other. In the present context an attempt has been
      made to study the influence of allelochemicals released by Parthenium on the
      growth, morphology and cytology of Helianthus annuus, both being strong
      allelopathic plants. The lower concentration of decomposed Parthenium leaves
      showed enhancing effect while higher doses depicted suppressive effect on growth
      and morphology of Helianthus annuus. However, cytological studies of pollen
      mother cells (PMCs) revealed increase in abnormality percentage with increasing
      concentration of allelochemicals. This study suggests better understanding of
      allelochemicals interaction and their incorporation into the betterment of crop.

PMID- 18831384
TI  - Macroinvertebrate colonization and breakdown of leaves in an astatic pond in
      south India.
AB  - Macroinvertebrate colonization and breakdown of Pongamia pinnata and Morinda
      tinctoria leaves were studied in an astatic pond in Madura College, Madurai.
      Morinda tinctoria leaves broke down fasterthan the leaves of P. pinnata.
      Breakdown capacities of astatic pond cannot be attributed to colonization of
      macroinvertebrates. Instead, microbial processing, and abiotic fragmentation are
      suggested as factors controlling breakdown rates. Tanypus sp (midgelarva) was
      abundant in leaf bags during the experimental period. This midge-larva appeared
      to use litter accumulations as a microhabitat that provided shelter and a rich
      supply of food in the form of organic matter Their abundance and regular
      occurrence of two leaves suggest that midge larvae enhance leaf fragmentation and
      possibly mediate the incorporation of organic matter in pond sediments once the
      plant tissue is sufficiently macerated.

PMID- 18831385
TI  - Impact of copper on haematological profile of freshwater fish, Channa punctatus.
AB  - The present study was to evaluate heavy metal toxicity stress symptoms in fish
      blood during long-term exposure of sublethal concentration of copper sulphate
      (CuSO4). The effects of copper on various heamatological parameters were
      evaluated exposing Indian fresh water fish, Channa punctatus to a sub-lethal
      concentration of copper sulphate (0.36 mg l(-1)) for different periods. Exposure
      of fish to copper showed a significant decrease in the haemoglobin (Hb) content
      from 10.73 to 6.60%, red blood cells (RBC) from 2.86 to 1.84 x 10(6)/mm3 and
      packed cell volume (PCV) from 31.00 to 23.33% at the end of 45th day as compared
      to control. Whereas the white blood cells (WBC) increased from 60.00 to 92.48
      x10(3)/mm3, clotting time (CT) from 27.66 to 43.00 second, erythrocyte
      sedimentation rate from 5.0 to 13.66 mm/hr and mean corpuscular volume from
      108.11 to 126.85 cmu, significantly, with increase in exposure periods. Although
      mean corpuscular haemoglobin concentration (MCHC) and mean corpuscular
      haemoglobin (MCH) values showed significant increase during 15 and 30 days
      exposures, both the values were found significantly increased at the end of the
      experimental period. The differential leucocytes count (DLC) showed a significant
      increase in the populations of lymphocytes and eosinophils, whereas neutrophils,
      monocytes and basophiles were found decreased after exposure to copper.

PMID- 18831386
TI  - Effect of malathion on reproductive system of male rats.
AB  - The pesticides are one of the most potentially harmful chemicals liberated in the
      environment in an unplanned manner Malathion is widely used as a potent pesticide
      in many countries and has been shown to produce some adverse health effects. A
      study was conducted to asses the effects of malathion on the male reproductive
      system of wistar rats. The pesticide was administered to rats orally at dose
      levels of 50, 150 and 250 mg/kg/body wt/day for 60 days. In comparison to the
      control rats, there was a significant reduction in the weight of testes,
      epididymis, seminal vesicle and ventral prostate. Testicular and epididymal sperm
      density were decreased in the animals treated with malathion. Pre and post
      fertility test showed 80% negative results after treatment Biochemical profile of
      the testis revealed a significant decline in the contents of sialic acid and
      glycogen. Whereas a significant increase in the protein content of testis and
      testicular cholesterol was observed. The activity of testicular enzyme acid
      phosphatase increased significantly while decreased alkaline phosphatase activity
      was found. Malathion also suppressed the level of testosterone significantly
      Results of the present study clearly suggest that malathion induce toxic effects
      on the male reproductive system of rats.

PMID- 18831387
TI  - Rove beetles (Coleoptera: Staphylinidae) collected during the long term
      ecological research in a Hungarian oak forest.
AB  - Along term ecological research was carried out in a Hungarian oak forest, in
      "Bukk" National Park starting with 1972. During the faunistical studies 3,602
      insect species and more than 200,000 individuals were collected. The dominant
      orders were Coleoptera (1,051 species), Lepidoptera (803 species), Hymenoptera
      (470 species) and Diptera (400 species). The relative species abundance (RSA) for
      all insects collected in all years of sampling period suggests a rather J shape
      curve than a not clear scaling property. This means that we were able to identify
      almost three quarters of the insect species from one ha European oak forest
      during the survey (from 1987 to 2003), and two third of the staphylinides
      expected. Considering the staphylinid fauna a total number of 160 species and
      4,022 individuals were collected. The most widely occurring species in dominance
      order were: Ocypus biharicus, Pseudocypus mus, Atheta gagatina, Philonthus
      quisquiliarius, Oxypoda acuminate, Platydracus chalcocephalus, Atheta
      crassicomis, Latrimaeum atrocephalum, Haploglossa puncticollis, Philonthus
      succicola and Anotylus mutator. The pooled value of alpha diversity was 1.51. The
      Shannon-Weiner Index (H') was relatively high (3.29) in comparison with other
      studies.

PMID- 18831388
TI  - Pollution level in distillery effluent and its phytotoxic effect on seed
      germination and early growth of maize and rice.
AB  - The effluent from a Lucknow- based distillery (Mohan Meakin Distillery) was
      analyzed for physico-chemical and biological parameters of pollution and
      concentration of potentially toxic heavy metals (Cd, Cr, Ni and Zn) and the
      effect of the distillery effluent, as such and on 50% dilution with tap water was
      studied on seed germination and seedling growth of maize (Zea mays L.) and rice
      (Oryza sativa L.). The effluent was wine red in colour and highly acidic (pH
      approximately 55) and possessed decaying alcoholic smell. The effluent contained
      high values of different pollution parameters, particularly total solids, 3450
      mgl(-1) (soluble plus suspended solids), alkalinity 1500 mgl(-1), biological
      oxygen demand (BOD, 1649 mgl(-1)) and chemical oxygen demand (COD, 2036 mgl(-1)).
      It had very low values of dissolved oxygen (DO, 0.34 mgl(-1)). The heavy metals
      (Cd, Cr, Ni and Zn) content, particularly the nickel concentration (0.029 mg l(
      1)) was high. Use of the distillery effluent, even on 1:1 dilution with tap water
      inhibited germination and early seedling growth of maize and rice. In both maize
      and rice, more so in the former germination % of seeds, length of radicle and
      plumule and the fresh and dry weight of the seedlings were significantly reduced.
      The emerging leaves of the seedlings also developed visible effects of toxicity
      some of which resembled the symptoms of nickel toxicity. Our observations suggest
      that the effluent, as discharged from the distillery carry a heavy load of
      pollutants. Its discharge into the river Gomti poses a potential threat to the
      aquatic life, perticularly during the summer months when the water flow in the
      river is drastically reduced. The distillery effluentis also harmful for
      irrigating crops grown along the drain carrying it.

PMID- 18831389
TI  - Abundance and seasonal variations of phytoplankton in the creek waters of western
      mangrove of Kachchh-Gujarat.
AB  - The phytoplankton was assessed quantitatively and qualitatively in regard to
      their abundance in creek waters at three sites along the western mangrove of
      Kachchh. In total one hundred and four species of phytoplankton were identified.
      Among them 82 species diatoms (Bacillariophyceae), 16 species dinoflagellates
      (Dinophyceae), 3 species blue greens (Cyanophyceae) and 2 species were green
      algae. The density in all the three sites varied from 94,166.67 to 2,44,500 cells
      l(-1). The salinity ranged from 36 to 44 per thousand, temperature 17 to 35
      degrees C and pH ranged from 7 to 8.9 respectively. These semi arid zone mangrove
      creek area having high densities were recorded during monsoon and early winter
      season.

PMID- 18831390
TI  - Histologic diagnoses of tissues from two nineteenth century Habsburgs.
AB  - This study describes the histological alterations of the internal organs of
      Prince Joseph Habsburg (1776-1847) and his first wife, Alexandra Pavlovna
      Romanova (1783-1801). Both corpses were mummified and the internal organs were
      stored separately in rosemary oil, in metal vessels. Royal Prince Joseph Habsburg
      died on 13 January 1847. The microscopic study confirms focal subacute
      glomerulonephritis (type Berg) with IgA precipitate on the glomerular mesangium
      and Bowmann's capsule. To the best of this author's knowledge, this is the first
      case in the paleopathological literature in which the subacute IgA
      glomerulonephritis could be confirmed immunohistochemically. Gout (urate
      nephropathy), severe arteriosclerosis, prostate adenoma and purulent prostatitis
      could also be diagnosed. The Prince's first wife, Alexandra Pavlovna Romanova,
      died in childbirth at age 18 years, along with her newborn daughter. Histological
      examination of Alexandra's organs revealed severe fibrocaseous and miliary
      tuberculosis, with dissemination to the lymph nodes, liver and spleen.

PMID- 18831391
TI  - Sister dispensers-- Australian trained nurses in pharmacy.

PMID- 18831392
TI  - Poison or perish. The rise of the pharmaceutical chemist in the late 1800s.

PMID- 18831393
TI  - Platform for success. Spacious site inspires design team's imagination.

PMID- 18831394
TI  - Environmental Services Department of the year 2008.

PMID- 18831395
TI  - Moving to digital. Taking the next leap in security surveillance.

PMID- 18831396
TI  - New tear, new regs. A look at the Joint Commission's standards for 2009.

PMID- 18831397
TI  - Medical home leading to greater collaboration. Multiplayer initiatives gain
      steam.

PMID- 18831398
TI  - Health literacy problem affecting the bottom line. Many in healthcare unaware of
      the issue.
AB  - Two health literacy experts discuss the issue, its effect on the healthcare
      system, and ways to improve health literacy.

PMID- 18831399
TI  - Project tests provider-based services.

PMID- 18831401
TI  - YMCA brings communities together to improve health.

PMID- 18831400
TI  - Report promotes community-based wellness programs. Modest outlay could bring
      positive ROI.
AB  - Investing $10 per person into community-based wellness programs each year could
      save the country more than $16 billion annually in healthcare costs within five
      years, according to a recent report released by the Trust for America's Health.

PMID- 18831402
TI  - Five questions with ... Ted Dacko.

PMID- 18831403
TI  - [Alcoholism: history is not finished...].

PMID- 18831404
TI  - [Biliary, pancreatic and systemic diseases associated with IgG4].
AB  - Whereas autoimmune pancreatitis is an established entity characterized by high
      serum concentrations of IgG4, IgG4 cholangitis is a quite new entity
      characterized by a massive infiltration of bile ducts by IgG4 positive
      lymphoplasmocytic cells. IgG4 cholangitis should therefore be differentiated from
      primary sclerosing cholangitis based on clinics, radiological and biological
      markers. This paper is aimed at reviewing all new aspects of diseases associated
      with high levels of IgG4.

PMID- 18831405
TI  - [Hepatitis C and insulin resistance].
AB  - In the course of a chronic infection with the hepatitis C virus, the fibrosis
      progression rate varies among individuals, and depends on the existence of
      certain co-factors. In this context, a growing interest has emerged and has
      focused on insulin resistance. In fact, the hepatitis C virus is now recognized
      as being responsible for a direct interference with the insulin signalling
      pathway. This insulin resistance of viral origin, in combination with an eventual
      insulin resistance associated with an existing metabolic syndrome, can therefore
      accelerate its evolution to a type II diabetes. Independently of its
      pathogenesis, insulin resistance occurring in chronic hepatitis C causes a fatty
      liver, contributes to the progression towards cirrhosis, and narrows the chances
      of a successful antiviral therapy. It is therefore crucial to recognize it in
      order to correct it.

PMID- 18831406
TI  - [New aspects of HEV infection].
AB  - The hepatitis E virus (HEV), known for being the cause of major outbreaks of
      waterborne hepatitis in Asia and Africa, is an emerging pathogen in
      industrialized countries. Virologic analyses of sporadic cases in Europe, Japan
      and the United States have shown that the origin of the infection was through
      autochthonous viral strains suggesting that the virus is present locally. In
      addition, transmission is not only enterically through contaminated water but
      also through ingestion of undercooked infected meat (swine or wild animals) or
      through infected blood products. Recently, a persistent HEV infection with
      chronic hepatitis and cirrhosis has been reported in patients with reduced immune
      surveillance as induced by chemotherapy or post-transplant immunesuppression.

PMID- 18831407
TI  - [Drug induced diarrhea].
AB  - Diarrhea is a frequent adverse event involving the most frequently antibiotics,
      laxatives and NSAI. Drug induced diarrhea may be acute or chronic. It may be due
      to expected, dose dependant properties of the drug, to immuno-allergic or bio
      genomic mechanisms. Several pathophysiological mechanisms have been described
      resulting in osmotic, secretory or inflammatory diarrhea, shortened transit time,
      or malabsorption. Histopathological lesions sometimes associated with drug
      induced diarrhea are usually non specific and include ulcerations, inflammatory
      or ischemic lesions, fibrous diaphragms, microscopic colitis and apoptosis. The
      diagnosis of drug induced diarrhea, sometimes difficult to assess, relies on the
      absence of other obvious causes and on the rapid disappearance of the symptoms
      after withdrawal of the suspected drug.

PMID- 18831408
TI  - [pH-impedancemetry: clinical implications].
AB  - Gastroesophageal reflux disease is a common condition that requires no additional
      exam if the diagnosis is straightforward and no complications is suspected. pH
      monitoring is often used for atypical symptoms or if there is no response to
      therapy with proton pump inhibitors. This was considered for decades as a "gold
      standard", but it shows many limits, especially because it only measures acid
      exposure. pH-impedance monitoring is a new technique that detects all types of
      reflux (gas-liquid and acid-weakly acid) and evaluates the relationship between
      symptoms and reflux events. It identifies patients with symptoms related to
      weakly acid reflux, that is not detected by conventional pH monitoring.

PMID- 18831409
TI  - [The future of "NOTES"].
AB  - In 2003, the first peroral appendectomy was carried out in a human subject. In
      order to prevent the premature adoption in clinical practice of the so-called
      "Natural orifice transluminal endoscopic surgery" (NOTES), a rational framework
      for its development was proposed in 2005. After animal experimentation, further
      abdominal interventions were carried out in humans (example: cholecystectomy)
      through the mouth, vagina, or in a combined approach. The main advantage of NOTES
      compared to laparoscopic surgery is, from the patient viewpoint, the absence of
      body scar, but other benefits (example: less pain and costs) could prove to be
      significant. It is impossible to predict whether or not NOTES will enter in
      routine clinical practice, but it will generate significant improvements for
      digestive endoscopy.

PMID- 18831410
TI  - [Disappearance of the patient's word behind the medical technique. Didier Sicard
      usefully in counter-current].

PMID- 18831411
TI  - [Practical problems of ECG in aged persons. Case No. 11].

PMID- 18831412
TI  - [Discovery of a gene mutation associated with familial neuroblastoma].

PMID- 18831413
TI  - [Lucky like the sellers of psychotropic drugs in France].

PMID- 18831414
TI  - [Blue tongue disease: mystery and hope (2)].

PMID- 18831415
TI  - [Insurance--disease: the strategy of the chaos].

PMID- 18831416
TI  - Combined viscocanalostomy-trabeculectomy for management of far-advanced glaucoma:
      evaluation of the early postoperative course.
AB  - BACKGROUND AND OBJECTIVE: To study the early postoperative efficacy and safety of
      combined viscocanalostomy with trabeculectomy (VISCO-TRAB) for treating far
      advanced glaucoma. PATIENTS AND METHODS: Patients with far-advanced glaucoma
      scheduled for glaucoma surgery were enrolled in the study. Surgery included
      viscocanalostomy until Schlemm's canal was deroofed and dilated with
      viscoelastic, followed by penetrating corneotrabeculectomy, peripheral
      iridectomy, and tight closure of lamellar flap. Patients with severe glaucoma who
      were treated with trabeculectomy only (TRAB) in the preceding year were used for
      comparison. RESULTS: The study included 39 eyes in the VISCO-TRAB group and 40
      eyes in the TRAB group. Mean intraocular pressure was significantly lower in the
      VISCO-TRAB group during the early postoperative period (P < .05). The
      postoperative course was less eventful in the VISCO-TRAB group with minimal
      hypotony or suture lysis-related complications. CONCLUSION: During the early
      postoperative period, VISCO-TRAB proved efficacious and safe in reducing
      intraocular pressure to target levels in patients with far-advanced glaucoma.

PMID- 18831417
TI  - Eyelid neoplasms in the Beijing Tongren Eye Centre between 1997 and 2006.
AB  - BACKGROUND AND OBJECTIVE: To examine the spectrum of eyelid neoplastic specimens
      obtained at the Beijing Tongren Eye Centre between 1997 and 2006. PATIENTS AND
      METHODS: A total of 2,639 eyelid neoplasms were included in the study. RESULTS:
      Of the 2,639 eyelid specimens, 2,276 (86.2%) were benign and 363 (13.8%) were
      malignant. The most common benign lesions were inflammatory lesions, melanocytic
      nevi, papillomas, dermoid and epidermoid cysts, and epithelial cysts. The most
      common malignant or semi-malignant tumors were basal cell carcinomas, sebaceous
      gland carcinomas, lymphomas, squamous cell carcinomas, and malignant melanomas.
      The mean age at diagnosis was 41 years for benign lesions and 60 years for
      malignant tumors. There was no significant gender predilection among the five
      major non-benign eyelid tumors. CONCLUSION: At the BeijingTongren Eye Centre
      between 1997 and 2006, the predominant non-benign eyelid tumors were basal cell
      carcinoma and sebaceous gland carcinoma, followed by lymphoma. The non-benign
      lesions occurred predominantly in elderly patients who were 60 years of age and
      older.

PMID- 18831418
TI  - Intraoperative adjustable suture strabismus surgery under topical and
      subconjunctival anesthesia.
AB  - BACKGROUND AND OBJECTIVE: To assess the postoperative surgical results of
      intraoperative adjustable suture strabismus surgery under topical and
      subconjunctival anesthesia. PATIENTS AND METHODS: For 44 patients who had
      undergone intraoperative adjustable suture technique under topical anesthesia,
      the deviations were measured preoperatively, at 1 day, 1 month, and 3 months
      postoperatively, and at the last postoperative follow-up visit. The mean follow
      up period was 7.8 months. RESULTS: Thirty-three patients had exotropia and 11 had
      esotropia. Mean age was 28.8 years. The success rates for exotropia and esotropia
      at the last follow-up visit were 81.8%. CONCLUSION: Intraoperative adjustable
      suture strabismus surgery under topical and subconjunctival anesthesia is the
      recommended surgical technique due to the successful results and various
      advantages compared with non-adjustable surgery, including the decreased rates of
      overcorrection or undercorrection that appear immediately after surgery and
      reoperation. Postoperative "drift" toward the original deviation was observed
      under longer follow-up periods than other studies.

PMID- 18831419
TI  - Sub-tenon's block: a national United Kingdom survey.
AB  - BACKGROUND AND OBJECTIVE: A survey was undertaken to ascertain current practices
      in ophthalmic regional anesthesia with an emphasis on sub-Tenon's block. Despite
      its increasing use, there are currently no guidelines for its explicit
      management. PATIENTS AND METHODS: An anonymized postal questionnaire survey was
      sent to 173 consultant anesthesiologist members of the British Ophthalmic
      Anaesthesia Society. RESULTS: Sub-Tenon's blocks were regularly performed by
      87.8% of respondents. The majority used a blunt metal cannula via the inferonasal
      quadrant. Local anesthetic was placed post-equatorially by 58% of respondents and
      deep posteriorly by 16.7%; 18% used vasopressors. There was no agreement for
      aseptic precautions, international normalized ratio, platelet levels, or venous
      access. Complications included vascular and muscular injuries, a case of
      fainting, and several cases of dysrhythmias. Current United Kingdom guidelines
      for monitoring patients were not being followed. CONCLUSION: These results show a
      need for robust national guidelines, especially in view of increasing use,
      indications, and potential risks of sub-Tenon's block.

PMID- 18831420
TI  - Lidocaine hydrochloride gel for ocular anesthesia: results of a prospective,
      randomized study.
AB  - BACKGROUND AND OBJECTIVE: This study evaluates the effectiveness of Akten (Akorn,
      Inc., Buffalo Grove, IL), a novel ophthalmic gel anesthetic agent for complete
      ocular anesthesia. PATIENTS AND METHODS: This study was conducted as a
      prospective, randomized, double-blinded, multicenter Phase III clinical trial to
      evaluate Akten gel. The study had four cohorts of subjects who received sham gel,
      Akten 1.5%, Akten 2.5%, and Akten 3.5%, respectively. Subjects were assessed for
      achievement of anesthesia at defined time intervals and questioned for "pain" or
      "no pain" following pinching of the conjunctiva with 0.3-mm forceps at
      predetermined intervals. RESULTS: A total of 209 subjects were entered into the
      study. The percentages of patients achieving the primary endpoint (ie, anesthesia
      within 5 minutes) were as follows: 22% for sham, 88% for Akten 1.5%, 89% for
      Akten 2.5%, and 92% for Akten 3.5%, respectively. Safety measures including
      corneal staining, conjunctival hyperemia, and eye pain with administra-tion were
      low and comparable in all cohorts. CONCLUSION: Akten gel appears to be an
      effective and safe ocular anesthetic. All doses were well tolerated and no dose
      related corneal toxicity was observed.

PMID- 18831421
TI  - In vivo laser confocal microscopic analysis of murine cornea and lens
      microstructures.
AB  - BACKGROUND AND OBJECTIVE: The purpose of the current study is to investigate in
      vivo microstructures of anterior segments of normal murine eyes by new-generation
      in vivo laser confocal microscopy. MATERIALS AND METHODS: Twenty-six corneas and
      lenses from 13 mice were analyzed by in vivo laser confocal microscopy. RESULTS:
      Murine corneal superficial cells formed a polygonal cell pattern, with a mean
      cell density of 577 +/- 115 cells/mm2 (mean +/- standard deviation). Corneal
      basal epithelial cells had dark cytoplasm and were closely organized (9,312 +/-
      1,777 cells/mm2). Sub-basal nerve fiber bundles were arranged in a whorl pattern,
      with both clockwise and counter-clockwise patterns. In the stroma, keratocytes
      were observed as numerous reflective stellate structures. The endothelial cells
      were organized in a honeycomb pattern (2,463 +/- 292 cells/mm2). Deeper inside
      the eye, murine lens epithelial cells were organized in a regular pattern (4,168
      +/- 636 cells/mm2) and numerous lens fibers were observed. CONCLUSION: In vivo
      laser confocal microscopy can provide high-resolution images of all corneal
      layers and lens structures of mice without sacrificing animals or tissue
      preparation.

PMID- 18831422
TI  - Surgical treatment of strabismus fixus associated with high myopia.
AB  - A 55-year-old woman had convergent strabismus fixus associated with high myopia.
      Bilateral medial rectus recession and loop myopexy of lateral and medial rectus
      muscles was performed. The clinical characteristics and the possible surgical
      treatment modalities were discussed. This surgery seems effective on both the
      restoration of dislocation of the eyeball and the improvement of ocular motility.

PMID- 18831423
TI  - Bioceramic orbital implant exposure repaired by a retroauricular myoperiosteal
      graft.
AB  - A patient with a painful, blind eye underwent enucleation and bioceramic orbital
      implantation. The bio-ceramic implant was wrapped with polyglactin 910 mesh and
      anteriorly capped with a scleral patch graft. Because there was tension on the
      wound, a relaxing conjunctival incision on the fornix was performed. Implant
      exposure with a diameter of 9 mm occurred 4 months after surgery. The exposed
      bioceramic implant was successfully repaired by a retroauricular myoperiosteal
      graft. The graft contains myofibrovascularized tissue, provides durable and
      vascularized coverage of exposed implants, and only requires a nearby harvesting
      site. The exposure completely resolved without recurrence after 2 years of follow
      up.

PMID- 18831424
TI  - Retrieval of a mispositioned Ex-PRESS glaucoma device.
AB  - The purpose of this article was to report the misposition and subsequent
      retrieval of an Ex-PRESS (Optonol Ltd., Neve Ilan, Israel) glaucoma drainage
      device implanted in an eye with pseudoexfoliative glaucoma. The formation of
      excessive fibrosis at the site of the implant, which was partly dislocated into
      the anterior chamber, was observed. The Ex-PRESS drainage device was removed from
      the anterior chamber and the intraocular pressure was relieved through
      trabeculectomy at the superotemporal part of the globe. The results suggest that
      trabeculectomy is a practical approach to alleviate intraocular pressure in the
      case of failed glaucoma drainage devices.

PMID- 18831425
TI  - Phthisis after endoscopic cyclophotocoagulation.
AB  - A 47-year-old man was treated with one session of endoscopic
      cyclophotocoagulation for uncontrolled, elevated intraocular pressure. Before
      treatment, the eye was quiet and uninflamed. Pretreatment visual acuity was 4/200
      and the intraocular pressure was 24 mm Hg. Treatment was applied to the ciliary
      processes for nearly 360 degrees. During the postoperative follow-up, the patient
      developed eye pain and persistent ocular inflammation. This ultimately led to
      phthisical changes evident 5 months postoperatively, when visual acuity was 1/200
      and the intraocular pressure was 7 mm Hg. Eighteen months after endoscopic
      cyclophotocoagulation, visual acuity was light perception and intraocular
      pressure was less than 1 mm Hg. Phthisis is among the complications that may
      result after treatment with endoscopic cyclophotocoagulation.

PMID- 18831426
TI  - Severe iritis and choroidal effusion following selective laser trabeculoplasty.
AB  - A patient with uncontrolled primary open-angle glaucoma underwent selective laser
      trabeculoplasty and developed a significant anterior chamber reaction, shallow
      anterior chamber, and choroidal effusion. Common complications associated with
      selective laser trabeculoplasty include conjunctival injection, mild anterior
      chamber reaction, and post-treatment intraocular pressure elevation. The authors
      believe this is the first reported case of severe iritis and choroidal effusion
      following selective laser trabeculoplasty.

PMID- 18831427
TI  - Multiple ocular abnormalities associated with trisomy 4p.
AB  - Ocular features associated with trisomy 4p have rarely been described. The
      authors have experienced multiple ocular abnormalities (bilateral cataracts,
      posterior synechiae, and posterior segment changes) associated with this
      chromosomal abnormality. It was presumed that these intraocular findings might be
      associated with the previous inflammatory process. In the current case, the
      patient recovered some useful vision after surgical removal of cataracts and
      intraocular lens implantations in both eyes. A detailed ophthalmic examination
      for patients with the autosomal imbalance is recom-mended.

PMID- 18831428
TI  - Jellyfish sting injury to the cornea.
AB  - A 25-year-old woman presented to the emergency room 2 hours after a jellyfish
      sting to the left eye. Centrally located linear epithelial defects were observed
      on slit-lamp evaluation. The epithelial defects improved but did not heal totally
      after meticulous patching with antibiotic ointment and cycloplegic drops. Small,
      subepithelial negative staining areas within the epithelial defects were observed
      on day 3. Confocal microscopy was performed and revealed thread-like
      hyperreflective structures, mainly located at the basal epithelial layer.
      Following debridement of the traumatized areas, the corneal epithelium healed
      completely in 24 hours, resulting in increased visual acuity and decreased
      foreign body sensation. Jellyfish stings to the eye may involve the intrusion of
      the nematocysts, thread-like venomous structures, into the cornea. Debridement of
      these foreign bodies can be helpful in the treatment of resistant cases.

PMID- 18831429
TI  - Novel therapeutic approach in the management of band keratopathy using amniotic
      membrane transplantation with fibrin glue.
AB  - A 91-year-old man with advanced glaucoma, status post trabeculectomy, and
      pseudophakia had a symptomatic recurrent band and bullous keratopathy in his left
      eye. Three previous ethylenediaminetetraacetic acid chelations with immediate
      recurrence of the calcic band keratopathy with frequent breakdown produced
      recurrent painful corneal epithelial defects. The calcified lesions were removed
      surgically, resulting in a smooth ocular surface. An 8-mm, 100-micron
      trephination was performed and a 360 degrees corneal lamellar peripheral
      dissection pocket was created. After covering the denuded corneal surface, the
      edges of the amniotic membrane were introduced into the pocket and secured using
      fibrin sealant. Additional amniotic membrane was glued to the nasal en temporal
      corneal areas and a collagen shield was applied. Wound healing was completed in
      10 days and a stable ocular surface was restored without pain or inflammation.
      During the follow-up period, no recurrence of the band keratopathy was observed.

PMID- 18831430
TI  - Double Descemet's membranes after penetrating keratoplasty with anterior segment
      optical coherence tomography.
AB  - An 83-year-old man underwent penetrating keratoplasty for pseudophakic bullous
      keratopathy in the left eye. Postoperatively, a thin transparent membrane in the
      anterior chamber was noted. The differential diagnosis included vitreous
      prolapse, retained capsule, fibrinous anterior chamber membrane, and retained
      Descemet's membrane in the anterior chamber, but the diagnosis was uncertain due
      to corneal edema and Descemet's membrane folds. Anterior segment optical
      coherence tomography was used to determine the diagnosis of retained host
      Descemet's membrane. This case report demonstrates that anterior segment optical
      coherence tomography is a useful and noninvasive instrument for diagnosing and
      following complications from penetrating keratoplasty.

PMID- 18831431
TI  - OCT and ultrasound biomicroscopic findings in iris arteriovenous malformation.
AB  - Iris arteriovenous malformation, also labeled as iris racemose hemangioma, is a
      rare condition in which abnormal vessels are present on the iris surface. Slit
      lamp findings in addition to anterior segment fluorescein angiographic features
      of such lesions have been described in the past. The authors report anterior
      segment optical coherence tomography and ultrasound biomicroscopic features in
      two patients with iris arteriovenous malformation.

PMID- 18831432
TI  - Dislocated posterior chamber intraocular lens scleral fixation technique through
      23-gauge vitrectomy cannulas.
AB  - A scleral fixation technique for posterior dislocated intraocular lens performed
      through 23-gauge vitrectomy cannulas is presented. It is based on the creation of
      polypropylene loops at opposite meridians through which haptics are engaged and
      placed in the sulcus. Repositioning of the intraocular lens (as opposed to
      substitution that requires new or reopening of corneal incisions) associated with
      microincisional vitrectomy techniques (23 gauge) allows for faster patient
      recovery. Free rotation of haptics through the loops aids in providing
      spontaneous good intraocular lens centering. The technique provides a minimally
      invasive solution for dislocated intraocular lenses after the unavoidable
      vitrectomy procedure to liberate the lens from the vitreous chamber.

PMID- 18831433
TI  - Ab interno sulcus placement of glaucoma tube implants.
AB  - A modified technique for sulcus placement of glaucoma silicone tubes is
      described. Sulcus placement can be useful in patients with penetrating
      keratoplasty or in those who are at risk for corneal endothelial decompensation.
      However, correct placement can be difficult to confirm with a traditional ab
      externo approach. An ab interno technique for sulcus placement of glaucoma tube
      implants that both offers an easier approach and facilitates accurate positioning
      is described.

PMID- 18831434
TI  - The use of intraoperative fluoroscopy as an aid for removal of radiopaque
      intraorbital foreign bodies.
AB  - Two patients with orbital trauma and intraorbital foreign bodies, as seen on a
      computed tomography scan, were taken to the operating room to rule out occult
      ruptured globe with possible foreign body removal. The C-arm fluoroscopic unit
      was employed to obtain real-time images of the foreign body's location in
      relation to the surgeon's dissection tools and the foreign body was extracted
      with minimal dissection and operating time. When removal of a foreign body is
      warranted, intraoperative fluoroscopy can help reduce surgical time and orbital
      manipulation.

PMID- 18831435
TI  - Preemptive sub-tenon's anesthesia for pars plana vitrectomy under general
      anesthesia: is it effective?

PMID- 18831436
TI  - [Ranking in health care results in wrong conclusions].

PMID- 18831437
TI  - [Problematic shortage of TBE vaccine. The vaccination interval might need
      adjustment].

PMID- 18831438
TI  - [Fibromyalgia internationally accepted concept. Pharmacological treatment now
      possible].

PMID- 18831439
TI  - [Tuberculosis outbreak in child day care center: 14 children infected. According
      to long-term follow up seven years later no late consequences].

PMID- 18831440
TI  - [Adverse drug reactions a common cause of hospitalization of the elderly. A
      clinical retrospective study].

PMID- 18831441
TI  - [Vitamin D and pregnancy: ethnocultural guidelines wanted].

PMID- 18831442
TI  - [Discontinuation of subsidizing of certain antihypertensive agents is not well
      thought-out].

PMID- 18831443
TI  - [Current pain treatment--no alternative for osteoarthritis patients with severe
      pain?].

PMID- 18831444
TI  - [Cognitive medicine: don't forget the trauma patients].

PMID- 18831445
TI  - [Mortality an uncertain indicator in quality comparisons].

PMID- 18831446
TI  - [Weight loss is the best treatment in obesity and obstructive sleep apnea
      syndrome].

PMID- 18831447
TI  - [Rabelais and Celine. Physicians, writers and language revolters 400 years
      apart].

PMID- 18831448
TI  - [Free psychiatric services from acting as prisons].

PMID- 18831449
TI  - [The only way to long life is to age].

PMID- 18831450
TI  - [Therapeutic vaccines against cancer and infectious diseases. Great possibilities
      in the research--small clinical progress so far].

PMID- 18831451
TI  - [Gene therapy in hereditary hearing loss. Future therapeutic possibility--maybe
      combined with stem cells].

PMID- 18831452
TI  - [Changing neurology--from diagnostic to therapeutic discipline].

PMID- 18831453
TI  - [Intensive media reporting following bus crash in Rasbo-Uppsala].

PMID- 18831454
TI  - [Coaching--a possible method in psychiatric care of young people. A project in
      which patients who have recovered from bipolar disorder coach newly diagnosed
      patients].

PMID- 18831455
TI  - [Increased risk of osteoporosis following treatment with SSRI?].

PMID- 18831456
TI  - [Representantives of the Swedish Neurological Association: Swedish neurology
      needs strong resource reinforcement].

PMID- 18831457
TI  - [Melatonin in delayed sleep phase disorder--why licensed?].

PMID- 18831458
TI  - [Who should be responsible for the treatment of type 2 diabetes?].

PMID- 18831459
TI  - [Large-scale falsification of prescriptions--who cares?].

PMID- 18831460
TI  - [Quality assurance in psychiatry jeopardized by short-term demands].

PMID- 18831461
TI  - [EpiPen delivers adrenaline intramuscullary--documented].

PMID- 18831462
TI  - [Eric Hermelin--"hospital servant" who translated Persian poetry].

PMID- 18831463
TI  - [Early Rheumatism Treatment].

PMID- 18831464
TI  - [Medical treatment of juvenile idiopathic arthritis].
AB  - Juvenile idiopathic arthritis is the most common chronic autoimmune disease. The
      outcome of this inflammatory disease is uncertain. Patients may suffer from
      severe joint damage leading to mutilations as well as from extraarticular
      manifestations. The prognosis is variable and depends in part on the number of
      affected joints and the occurrence of extraarticular manifestations.
      Pharmacomedical treatment has changed markedly in the last decade. It consists of
      a combination therapy including nonsteroidal antirheumatics, glucocorticoids
      either systemic or intraarticular, classical disease modifying drugs like
      sulfasalazine and methotrexate as well as leflunomide and biologicals. These new
      therapeutic strategies have effected dramatic improvements also in patients with
      severe, so far intractable disease. The TNF inhibitors etanercept and adalimumab
      have succeeded in double blind controlled trials, while infliximab failed to show
      significant superiority over placebo. Further treatment options include
      inhibitors of interleukin 1 (anakinra and rilonacept), interleukin 6
      (tocilizumab) and inhibitors of T-cell activation (abatacept). This review will
      summarize the pharmacotherapeutic options based on studies published in the
      literature.

PMID- 18831465
TI  - [Insomnia].
AB  - Insomnia is a highly prevalent disorder with consequences for the patient's
      physical and mental health, daily function, and job performance. This paper gives
      an overview on current and new pharmacological treatments of insomnia.
      Additionally, some evidence based treatment options with regard to cognitive
      behavioral therapy are presented.

PMID- 18831466
TI  - [Surveillance--more than a marketing instrument?].

PMID- 18831467
TI  - [Medicine in space. An organism under exceptional circumstances].

PMID- 18831468
TI  - [Food allergies. Package information is of little value].

PMID- 18831469
TI  - [Local Treatment of stomatitis aphthosa].

PMID- 18831470
TI  - Quality healthcare for America's children, Part 2.

PMID- 18831471
TI  - Closing the gap in children's quality measures: a collaborative model.
AB  - The need for measures of the quality of healthcare provided to children and
      adolescents is well documented. However, children have been underrepresented in
      national healthcare quality measurement and reporting efforts. The Pediatric Data
      Quality Systems (Pedi-QS) Collaborative is addressing this gap. Two consensus
      measure sets and an assessment of nursing-sensitive indicators in pediatric care
      have been produced through the collaborative. The framework and measure set
      development process are described. Lessons learned from applying the process are
      summarized, and future directions are suggested. Voluntary collaborative efforts
      are vital for advancing children's measures, and national support and funding are
      also needed.

PMID- 18831472
TI  - Interdisciplinary analysis of chemotherapy preparation at a pediatric hospital.
AB  - This report represents the results of an interprofessional investigation of the
      pharmaceutical procedures for hematology and oncology at a pediatric hospital.
      Pharmacists and industrial engineers identified areas for improvement, including
      a reduction in the interruption of regular pharmaceutical operations for the
      expedited preparation of chemotherapy treatments and the development of more
      robust drug preparation procedures that would ensure medication safety. The
      establishment of a satellite hematology/oncology pharmacy was also examined.
      Procedural changes were proposed in an effort to increase the safety and service
      levels of chemotherapy treatments for patients with hematological and oncological
      disorders.

PMID- 18831473
TI  - Communicating the death of a child in the emergency department: managing
      dialectical tensions.
AB  - This study highlighted the tensions that physicians face when communicating the
      death of a child to parents. Ten pediatric physicians participated in interviews
      in which they were asked to provide specific details about end-of-life
      discussions they have had with families in pediatric emergency rooms. From these
      findings, it is evident that physicians are required to balance multiple external
      and internal tensions embedded in these difficult conversations.

PMID- 18831474
TI  - Interview with a quality leader: Uma Kotagal on advances in pediatric quality.
      Interviewed by Christy L Beaudin.

PMID- 18831475
TI  - Pressure ulcer development in infants: state of the science.
AB  - The science of pressure ulcer development in infants is underdeveloped. Although
      recent conceptual frameworks have been applied to younger populations, this
      article focuses on the unique attributes of full-term and preterm newborns that
      have an impact on pressure ulcer development. A proposed schema identifies the
      theoretical elements associated with pressure ulcer development in infants.

PMID- 18831476
TI  - Gaps in pediatric clinician communication and opportunities for improvement.
AB  - Teamwork and good communication are central to the provision of high-quality
      care. A standardized focus-group protocol was used. Analysis assessed emergent
      themes of patient safety-related effective and problematic clinician
      communication. Sixty-three focus groups were conducted with clinicians from five
      Chicago Pediatric Patient Safety Consortium hospitals. Effective and problematic
      clinician-to-clinician communication themes were described in all focus groups
      and at each participating hospital. Problematic communication contexts included
      the communication process for orders, consultations, acuity assessment,
      management of surgical and medical patients, and the discharge process.
      Organizational policies and systems leading to patient safety risk included a
      lack of clear responsibilities and expectations for clinicians and for clinical
      communication, as well as a lack of a clear chain of responsibility for
      communication when hierarchical communication barriers affected safe patient
      care. Results of this investigation highlighted gaps in pediatric clinician
      communication and opportunities for improvement.

PMID- 18831477
TI  - Finding the right words: using the terms allow natural death (AND) and do not
      resuscitate (DNR) in pediatric palliative care.
AB  - When children are dying in a hospital setting, healthcare providers need to help
      families make important end-of-life care decisions. Most providers use the term
      do not resuscitate (DNR) when suggesting a course of action that involves not
      using extraordinary lifesaving measures. Some healthcare providers use the term
      allow natural death (AND) to discuss this same approach. This study investigated
      pediatric healthcare providers' beliefs about using AND as opposed to DNR.
      Results revealed that providers believe the term AND is somewhat ambiguous but
      may be more family centered.

PMID- 18831478
TI  - Courage and character, leaders and legends: an interview with Thomas Starzl, MD,
      PHD.

PMID- 18831479
TI  - A model for structuring the donor discussion in emergent transplant procedures.
AB  - OBJECTIVE: To investigate the potential for maximizing organ and tissue donation
      by identifying an empirical basis for structuring donor discussions. DESIGN:
      Intentions to donate organs and tissues were recorded in 2 separate samples of
      participants and analyzed separately by using Guttman scaling, the second sample
      providing a replication of the findings from the first. PARTICIPANTS: 304
      participants were recruited from the Royal Society Summer Science Exhibition
      2004, and 200 health professionals were recruited from the Royal Free Hospital.
      RESULTD: High coefficients of scalability and reproducibility in both samples
      indicate a one-dimensional scale for intentions to donate organs and tissues,
      with solid organs more likely to be donated than corneal, hand, and facial
      tissue. Thus donor discussions can be structured in a robust order, with the
      potential for reliable use of cutoff points once donation of a particular organ
      or tissue has been refused. CONCLUSIONS: This reliable pattern can be used to
      maximize organ and tissue donation rates and to underpin emergent transplant
      techniques.

PMID- 18831480
TI  - Modified technique for recovering aortoiliac homografts.
AB  - BACKGROUND: Infection of the prosthetic aortic graft bypass remains one of the
      most serious complications of aortoiliac bypass grafts. Use of an aortoiliac
      allograft as a replacement for an infected prosthetic graft is an effective
      treatment for this problem. However, the availability of aortoiliac grafts is
      affected by the high rate of procurement errors experienced during recovery. This
      overall error rate nationally averaged 32.5% in 2006, of which nearly a third
      (9.6%) were related to tears of the intima at or below the bifurcation of the
      abdominal aorta. OBJECTIVE: To analyze the potential of a new aortoiliac graft
      recovery method in reducing the error rate. METHOD: A modified technique of
      aortoiliac graft recovery was used to minimize the possibility of intimal tears.
      The essence of this technique is to change the sequence of mobilization of the
      graft, starting from the zone of low resistance, which is at the iliac arteries,
      and continuing upward to the abdominal aorta, which has higher resistance because
      of the greater thickness of the aortic wall. An additional modification of the
      standard technique is to use a tourniquet to raise the aortic edges. CONCLUSION:
      The aortoiliac graft has various resistances to tearing owing to the different
      wall thicknesses of the aorta and the iliac arteries. Mobilization of the
      abdominal aorta before dissection of the iliac arteries creates a high risk of
      tears at and around the bifurcation of the aorta and the iliac arteries.

PMID- 18831481
TI  - Comparative analysis of clinical efficacy and cost between University of
      Wisconsin solution and histidine-tryptophan-ketoglutarate.
AB  - OBJECTIVE: To compare University of Wisconsin solution (Viaspan), the universal
      standard for organ preservation, with histidine-tryptophan-ketoglutarate
      solution. An analysis of each solution, in reference to clinical trials with
      specific organs, is presented and assessed to find the efficacy of each in a
      clinical environment. Also to view each solution from an economical standpoint,
      and in the end develop an overall understanding of the key similarities and
      differences between each solution in order to assess appropriate use of each in a
      clinical setting. DATA SOURCES: A literature search was conducted by using
      PubMed, MEDLINE, BIOSIS, Embase, and other online data bases to find the most
      recent studies of University of Wisconsin and histidine-tryptophan-ketoglutarate
      solutions. Search terms included University of Wisconsin solution, histidine
      tryptophan-ketoglutarate, preservation solution, cost analysis, biliary
      complication, and other related subjects. STUDY SELECTION: Previous research was
      selected from the literature search to provide basic information on the 2
      solutions and also to provide clinical examples of each solution and the efficacy
      of each with specific organs. DATA SYNTHESIS: Information and published articles
      on the 2 solutions were gathered for descriptive and comparative purposes.
      CONCLUSIONS: The 2 solutions appear equally effective in organ preservation. Each
      solution has its own organ-specific qualities, and each has different
      complications. The studies reviewed here indicate that the differences are minor
      and thus suggest that the 2 solutions are equally acceptable for clinical use. Of
      the 2 solutions, histidine-tryptophan-ketoglutarate costs less than University of
      Wisconsin solution.

PMID- 18831482
TI  - An analysis of critical care staff's attitudes to donation in a country with
      presumed-consent legislation.
AB  - CONTEXT: Lack of knowledge and confidence among critical care staff in
      identifying potential donors and communicating with donor families may explain
      missed organ and tissue donations. OBJECTIVES: To elucidate attitudes of critical
      care staff toward donation and their knowledge, involvement, and self-reported
      skills and confidence levels with donation-related tasks. METHODS: Between
      January 2004 and May 2006, Donor Action Foundation's Hospital Attitude Survey was
      used to collect data from staff members in critical care units in our university
      hospital (study group) and 2 other Belgian university hospitals (control group).
      In total, 92 physicians, 433 nurses, and 26 other staff members participated.
      RESULTS: The 2 groups did not differ significantly with regard to donation
      related attitudes. The study group had a significantly lower perception of the
      public's approval of organ donation than did the control group (P < .001). Nurses
      reported significantly less involvement than did physicians (P < .001) in caring
      for potential donors, communicating severe brain damage, explaining brain death,
      requesting donation, and contacting procurement staff. Probably because of
      previous training, physicians in the study group reported less need for
      additional training on donation-related issues than did control physicians.
      However, compared with physicians, nurses in the study group requested
      significantly more training on a number of donation tasks. Nurses with more than
      5 years of critical care experience were consistently more confident with
      donation-related tasks. CONCLUSION: Support rates for donation are high overall,
      and previous training is associated with improved attitudes and decreased
      educational needs. Educational efforts tailor-made for nurses should increase
      nurses' confidence levels when confronted with potential donors and their next of
      kin.

PMID- 18831483
TI  - Does family disagreement affect donation decisions by next of kin?
AB  - CONTEXT: Information about the relationship between family disagreement and
      donation decisions may facilitate development of strategies to help families
      resolve conflict and possibly increase donation consent rates. OBJECTIVE: To
      assess how family interactions influence next-of-kin decisions about organ
      donation. DESIGN: Semistructured survey. SETTING AND PARTICIPANTS: Next of kin of
      potential donors (147 donors, 138 non-donors) from 1 organ procurement
      organization participated in a semistructured telephone interview, answering
      questions about the presence and influence of others during decision making
      related to organ donation. RESULTS: When others were actively involved in the
      donation decision (68%), disagreement about the donation decision occurred in 32%
      of cases. Compared with families initially in agreement, families not in
      agreement were less likely to donate (P < .001), took longer to make a decision
      (P < .001), and were less likely to make the same decision now (P < .001). Family
      disagreement was significantly associated with having more family members
      involved in the discussion, characteristics of the deceased (younger age, not
      married, nonwhite race, fewer days in the hospital, trauma-related death), next
      of-kin characteristics (less education, less favorable organ donation beliefs),
      not knowing the deceased's donation intentions, less satisfaction with the health
      care team, and perceptions of a less compassionate donation requester.
      CONCLUSIONS: Family disagreement occurred in one-third of donation approaches
      when other family members were present. Such disagreement is most likely to
      contribute to donation refusal when the deceased's donation intentions are
      unknown. Recognizing and assessing the nature of family disagreement may increase
      donation consent.

PMID- 18831484
TI  - Roller coaster marathon: being a live liver donor.
AB  - The purpose of this phenomenological study was to examine the meaning of being a
      live liver donor. Six people between ages 27 and 53 years participated. A
      qualitative, in-depth, semistructured interview format was used to explore
      donors' thoughts and feelings about being an organ donor. Five themes were
      identified: (1) no turning back--how do I live without you? (2) roller coaster
      marathon, (3) donor network, (4) the scar, and (5) reflections--time to think. At
      the center of the experience was the donor's commitment to the recipient. Once
      donors began the process, they were determined to see it through. The process was
      complex, and donors received various levels of support from family, friends,
      health care professionals, and others. After donation, as donors recovered and
      were able to resume their usual daily responsibilities, they reflected on the
      impact of the experience and how it changed their view of life.

PMID- 18831485
TI  - The relationship between the sick role and functional ability: one center's
      experience.
AB  - OBJECTIVE: To determine the impact of the sick role on posttransplant functional
      ability. METHODS: A convenience sample of 97 kidney transplant recipients (mean
      age, 45.8 years; SD, 12.8 years; 47% female; 68% African American) participated
      in this exploratory cross-sectional study. Self-report data were collected during
      a posttransplant clinic visit via the Response to Illness Questionnaire used to
      measure sick-role perceptions, the Functional Status Questionnaire used to
      measure functional ability, and an investigator-developed Demographic Data Sheet
      used to measure sociodemographic data and comorbidities. RESULTS: Factor analysis
      of the Response to Illness Questionnaire yielded 7 distinct factors that
      accounted for 62.2% of total score variance. Multiple regression analysis
      indicated a significant relationship between those 7 factors and the 5 factors
      revealed by the Functional Status Questionnaire. Demographic factors that also
      correlated with the functional status factors included type of work, gender, age,
      education, and donor source. Coping with illness and Resentment of illness were
      the strongest predictors of functional status in this sample. Patients with the
      strongest coping skills and the least resentment of illness consistently showed
      more advanced functional abilities. CONCLUSIONS: Results suggest that individuals
      who have the strongest coping skills and the least resentment toward their
      illness seem best able to gain strength and reject the sick role as a permanent
      identity. Health care providers must acknowledge patients' illness perceptions
      and design interventions focused on optimizing functional ability in vulnerable
      transplant recipients.

PMID- 18831486
TI  - Seatbelt injury resulting in functional loss of a transplanted kidney.
AB  - The transplanted kidney, lying heterotopically in the iliac fossa, is especially
      vulnerable to damage from blunt trauma, particularly compression by vehicle
      seatbelt. We present a case wherein a functioning renal allograft lying in the
      right iliac fossa was severely injured by seatbelt compression, resulting in
      significant functional compromise and eventual loss. The patient later underwent
      successful retransplantation with a second living donor kidney. Management of
      injured renal transplant recipients requires appreciation of mechanisms likely to
      cause damage to the graft, as well as familiarity with available treatment
      options, both surgical and nonsurgical. As functional life spans of renal
      allografts improve, this type of injury will most likely be encountered with
      increasing frequency.

PMID- 18831487
TI  - Patients seeking alternatives to the long waiting list: a reality faced by
      transplant physicians.
AB  - The need for deceased donor organs for kidney transplantation in the United
      States continues to increase. The increasing demand has fueled desperate attempts
      by patients to circumvent the long waiting list of the United Network for Organ
      Sharing. We report 4 patients with end-stage kidney disease who sought and
      obtained a live donor kidney transplant outside the United States. In each case,
      a nephrologist was following up with the patient regularly. Each patient
      experienced significant unexpected adverse events after the transplant surgery.
      Desperate attempts to obtain an organ are common and are likely to continue.
      Although patients with end-stage renal disease who obtain an organ transplant at
      an unregulated transplant center can have successful outcomes, transplant
      physicians should be aware of the common practice and should advise their
      patients of potential complications associated with acquisition of organs through
      means that circumvent standard oversight by the United Network for Organ Sharing
      and by institutions.

PMID- 18831488
TI  - Nursing and transplant coordination: a call for clarity.
AB  - Organ transplantation is a complex and highly regulated field. This review
      focuses on the role of nurses and transplant coordinators in solid organ
      transplantation, excluding both inpatient staff nursing and procurement
      activities. The literature describes a robust and autonomous transplant
      coordinator role; a key member of the multidisciplinary transplant team.
      Transplant coordinators facilitate patient care throughout all phases of
      transplantation. However, a lack of consensus on licensure and educational
      preparation of these important practitioners was evident from the review of
      literature. Synthesis of the data suggests that the role of transplant
      coordinator is not distinct but a description of a wide variety of functions,
      duties, and tasks that require varying levels of licensure and educational
      preparation. Greater clarity for both practitioners and consumers could be
      achieved by creating certification levels similar to nephrology nurses. As no
      transplant-specific staffing models or benchmarks were discovered, rigorous
      research regarding optimal staffing patterns is also recommended.

PMID- 18831489
TI  - Go West, young tech.

PMID- 18831490
TI  - The blood bank: whole lotta shakin' goin' on. Blood-bank support in U.S. military
      operations.

PMID- 18831491
TI  - POL sets precedent when lab opens transfusion services.

PMID- 18831492
TI  - The impact of QC frequency on patient results.
AB  - The expected number of unacceptable patient results due to an undetected,
      malfunction--E(Nu)--can be set as a patient-based quality goal. Using the number
      of patients tested between QC specimens as a design parameter allows one to
      design QC strategies that meet specified patient-based quality goals. The QC
      utilization rate can be minimized in a QC design for a given E(Nu). The QC
      utilization rate achievable depends on how close analytical imprecision is to the
      total allowable error.

PMID- 18831493
TI  - Blurred lines of surgical, cytology, and molecular pathology reporting.

PMID- 18831494
TI  - Is your lab rep selling a commodity?

PMID- 18831495
TI  - Can AWAs meet the lab's needs?

PMID- 18831496
TI  - United laboratory industry stops CBD project.

PMID- 18831497
TI  - Frontiers of minimally invasive thoracic surgery. Preface.

PMID- 18831498
TI  - The variability of practice in minimally invasive thoracic surgery for pulmonary
      resections.
AB  - Thoracic surgeons participating in this survey seemed to have clearly indicated
      their perception of VATS major lung resections, in particular VATS lobectomy. 1.
      The acronym VATS as a short form of "video-assisted thoracic surgery" was the
      preferred terminology. 2. According to the respondents, the need or use of rib
      spreading served as the defining characteristic of "open" thoracic surgery. 3. It
      was most commonly suggested that VATS lobectomy is performed by means of two or
      three port incisions with the addition of a minithoracotomy or access incision.
      4. Rib spreading (shearing) was not deemed acceptable as part of a strictly
      defined VATS procedure. 5. Although there was no general consensus, respondents
      suggested that the preferred approach for visualization in a VATS procedure was
      only through the video monitor. 6. Although minimally invasive procedures for
      lung resection are still mainly being used for diagnostic and minor therapeutic
      purposes, young surgeons seemed to be more likely to recommend VATS lung surgery
      for major pulmonary resections than their more senior colleagues. 7. The survey
      confirmed that the use of the standard posterolateral thoracotomy is still
      widespread. Almost 40% of the surgeons claimed to use the standard posterolateral
      thoracotomy for more than 50% of their cases and less than 30% use it for less
      than 5% of cases. 8. The major reasons to perform VATS lobectomy were perceived
      to be reduced pain and decreased hospitalization. 9. Approximately 60% of the
      surgeons claimed to perform VATS lobectomy in less than 5% of their lobectomy
      cases. Younger consultants reported using VATS lobectomy in up to 50% of their
      lobectomy cases. There was the suggestion that lack of resources could justify
      the minor impact of VATS lobectomy in the thoracic surgical practice in middle-
      to low-income countries. 10. The currently available scientific evidence on
      safety and effectiveness, and technologic advancements were emphasized as the two
      factors having a major impact on the development of minimally invasive thoracic
      surgical practice. 11. Any lack of popularity of VATS lobectomy was presumed to
      be caused by several equally important factors. Resistance to change by more
      senior surgeons ranked highly among younger surgeons, however, as an explanation
      for the slow adoption of this technique. Senior surgeons. however, seemed to
      focus their attention on the steep learning curve of VATS lobectomy. In addition,
      surgeons from middle- to low-income countries recognized certain financial and
      logistic difficulties as major determinants of the lack of popularity of VATS
      lobectomy. 12. Most surgeons thought that robotic thoracic surgery represented an
      evolution of VATS. Nevertheless, almost 30% did not think current robotic methods
      meet the criteria for minimally invasive surgery. More than 90% of the
      participants stated that they did not perform robotic thoracic surgery. This was
      reportedly because of costs. but also because of the fact that robotic approaches
      have not yet demonstrated a distinct advantage over nonrobotic VATS procedures.
      13. It was suggested that in every unit or department there should be at least
      one surgeon with a specific interest and capability in VATS lobectomy. The
      younger surgeons. however, seemed to envisage more widespread competency being
      optimal. 14. Most suggested that training in VATS lobectomy be done in a stepwise
      fashion starting from the classical open technique. Older surgeons wanted to see
      this as an extracurricular activity following completion of the current training
      curriculum rather than included in the traditional training program. In the
      opinion of the thoracic surgeons taking part in this survey, pulmonary resections
      not performed according to these standards could not be called VATS procedures
      but should be included within the MITS category at large, along with other
      diagnostic and therapeutic interventions. In addition, the survey confirmed that
      the time-honored muscle-dividing thoracotomy is still widely used. The
      opportunity for a progressive move toward the routine use of less invasive
      approaches for major pulmonary resections, however, is already well within sight.
      Given the results of the ESTS survey supporting a stepwise teaching process
      leading to VATS lobectomy, hybrid and minimally invasive open lung resections
      (discussed elsewhere in this issue) collectively defined as MITS may serve as
      starting point in this process to expand the appropriate use of VATS lobectomy in
      the modern thoracic surgical practice.

PMID- 18831499
TI  - VATS lobectomy is better than open thoracotomy: what is the evidence for short
      term outcomes?
AB  - VATS lobectomy is an acceptable alternative to open lobectomy for treating early
      stage NSCLC. Although no large randomized control trial has compared these
      procedures, recent large series and case-control studies provide strong evidence
      that patients undergoing VATS lobectomy have less pain, fewer perioperative
      complications, shorter chest-tube duration, and decreased length of stay.
      Increasing evidence supports improved quality of life up to 1 year, less
      inflammation, and greater safety profile in high-risk patients. More data are
      needed to better show an improvement in the economic efficacy, ability to more
      effectively administer adjuvant therapies, and benefit of robotic assistance in
      VATS lobectomy.

PMID- 18831500
TI  - Long-term outcomes of thoracoscopic lobectomy.
AB  - Thoracoscopic lobectomy is emerging as the procedure of choice for patients with
      early stage non-small cell lung cancer, based on advantages in quality of life as
      well as long-term outcomes. In addition, thoracoscopic lobectomy has been
      demonstrated to be safe and effective for selected patients with locally advanced
      disease and for those after induction therapy. Concerns relating to oncologic
      efficacy, as measured by complete resection rate, ability to perform complete
      mediastinal lymph node dissection, or cancer-specific survival, have not been
      supported by evidence in the literature. In addition there is increasing evidence
      that thoracoscopic lobectomy may actually have superior outcomes, based on
      advantages in morbidity and mortality after resection and in the delivery of
      adjuvant chemotherapy.

PMID- 18831501
TI  - Video-assisted thoracic surgery lobectomy: centers of excellence or excellence of
      centers?
AB  - VATS lobectomy, as defined by CALGB 39802, provides the same oncologic surgery as
      that performed through a thoracotomy. Standardizing the terminology is the first
      step that must be undertaken to standardize the operation. VATS lobectomy is the
      use of technology to aid in performing an established procedure. This technology
      and development of the skills required to perform a safe VATS lobectomy must be
      carefully monitored to protect the quality of the product, which ultimately is
      defined as patient outcome. "Center of Excellence" is a determination used in
      several other specialties to provide quality assurance for new procedures or
      technologies, or for those surgeries not widely performed, such as esophageal
      surgery. The authors believe that the profession should designate Centers of
      Excellence based on the credentialing guideline discussed earlier. The authors do
      believe that the current residency and fellowship training will provide, in time,
      ample surgeons skilled in VATS lobectomy. As these surgeons become certified and
      disseminate throughout the country, it is expected that VATS lobectomy will be
      readily available in most institutions. Over time this will allow VATS lobectomy
      to evolve from specific Centers of Excellence to a broader group of hospitals
      based on widespread availability ofa surgeon certified in VATS lobectomy. During
      this transition, the authors would encourage the community of surgeons performing
      this procedure to submit their statistics to a nationwide database. This will
      provide an excellent database for evidence-based medicine. Such rigorous data
      collection should permit thoracic surgeons to be appropriately compensated for
      performing these technically challenging procedures.

PMID- 18831502
TI  - Minimally invasive open surgery approach for the surgical resection of thoracic
      malignancies.
AB  - This article describes minimally invasive open surgery for resection of
      intrapulmonary malignancies. This approach compensates for the weak points of
      video-assisted thoracic surgery while remaining minimally invasive. Overall, it
      is respected as a technically feasible alternative to conventional lobectomy by
      way of open thoracotomy with an acceptable range of morbidity or mortality.

PMID- 18831503
TI  - Complications and learning curves for video-assisted thoracic surgery lobectomy.
AB  - Surgery remains the mainstay for the treatment of lung cancer. While pulmonary
      resection has been safe for years, there is a trend toward minimally invasive
      (VATS) pulmonary resections. Studies have now shown that standard complete cancer
      operations performed via VATS offer patients a shorter hospital stay and quicker
      recovery without compromising the cure rate for an operation performed via a
      thoracotomy.

PMID- 18831504
TI  - The VATS lobectomist: analysis of costs and alterations in the traditional
      surgical working pattern in the modern surgical unit.
AB  - It is beyond the scope of this article to review the advantages of VATS
      lobectomy, but the data in support of this technique are increasing
      progressively. There is excellent evidence to support the oncologic equivalence
      and safety profile as compared with open thoracotomy, and data that demonstrate
      the reduced pain associated with VATS resection. Also, reduction in immune
      disturbance provides a tantalizing glimpse of one additional potential modality
      of benefit for less traumatic surgery. Unfortunately, in the economic world,
      equivalence, preferably with less cost, is the test applied. Whatever the
      societal benefit of improved quality of life following surgery, this has no cost
      benefit attached. From the foregoing discussion one can conclude that VATS
      lobectomy is no more costly than open resection and does generate additional
      hospital beds. The authors remain uncertain as to the preferred form of VATS
      lobectomy but it seems that the reduced trauma of the endoscopic procedure is
      associated with more benefit in terms of shorter hospitalization albeit at the
      cost of some increase in operating time. VATS techniques and lobectomy sit
      comfortably within the structure of any thoracic unit requiring little adjustment
      to established process. It is likely that ultimately 30% or thereabouts of major
      pulmonary resection will be undertaken using this technique and that VATS
      interventions will aid patient assessment regardless of stage or ultimate
      intended therapy. Competency and responsible use remain paramount considerations.

PMID- 18831505
TI  - Robotically assisted lobectomy: learning curve and complications.
AB  - The past two decades have witnessed a revolutionary transition in surgical
      technique and technology with the development of minimally invasive approaches.
      Many advantages were obtained by using video-assisted thoracoscopic surgery: less
      surgical trauma and pain, shorter hospital stay, and satisfactory cosmetic
      results. Limitations still remain, however, because of impaired vision,
      restricted instrument-maneuverability, unstable camera platform, and poor
      ergonomics for the surgeon. Some of the more prominent limitations involve the
      technical and mechanical nature of the equipment. This article describes
      technical aspects, learning curve, and complications in the field of robotic
      lobectomy.

PMID- 18831506
TI  - Cost comparison of robotic, video-assisted thoracic surgery and thoracotomy
      approaches to pulmonary lobectomy.
AB  - The financial impact of employing minimally invasive techniques for lobectomy
      compared with traditional open thoracotomy was assessed. A retrospective review
      was conducted using ICD9 codes for thoracotomy, video-assisted thoracic surgery
      (VATS), and robotic VATS lobectomy to determine total average costs associated
      with the resultant hospital stay. The difference in total average costs was
      calculated for each group. Robotic VATS lobectomy had higher associated costs
      than VATS only, primarily attributed to increased costs of the first hospital
      day, but was still less costly than thoracotomy. The average cost of VATS is
      substantially less than thoracotomy primarily because of a decreased length of
      stay. The cost of robotic assistance for VATS is still less than thoracotomy, but
      greater than VATS alone.

PMID- 18831507
TI  - Does minimally invasive thoracic surgery warrant fast tracking of thoracic
      surgical patients?
AB  - Fast-tracking protocols or postoperative care computerized algorithms have been
      shown to reduce hospital LOS and reduce costs for patients. who undergo both open
      and VATS procedures The ability to fast-track is not governed by the type of
      procedure (closed versus open), but rather by patient characteristics and the
      mindset of the operating surgeon and the postoperative care team. While use of
      protocols enhance the ability of many physicians to fast-track many different
      types of patients, it is a mistake to force these protocols on all patients
      because, if not modified, they can lead to increased complications, readmissions,
      and low patient and family satisfaction. By carefully analyzing surgical results
      using accurate prospective databases, the types of patients who fail fast
      tracking and the reasons they fail can be identified. Specific changes to the
      postoperative algorithms can be implemented and these alterations can lead to
      improved outcomes. For example, we have shown that by using pain pumps instead of
      epidurals in elderly patients we can improve outcomes and still fast-track
      octogenarians with minimal morbidity and high patient satisfaction. We have also
      shown that the use of increased physical therapy and respiratory treatments
      (important parts of the care of all patients after pulmonary resection, but a
      limited resource in most hospitals) may also lead to improved surgical results
      for those with low FEV1% and DLCO%. Although fast-tracking protocols cannot be
      applied to all, the vast majority of patients who undergo elective pulmonary
      resection, even those at high risk, can undergo safe, efficient and cost-saving
      care by way of preset postoperative algorithms after VATS or thoracotomy
      procedures. When the typical daily events are communicated each morning and the
      planned date of discharge is reinforced with the patient and family before
      surgery and each day in the hospital on rounds, most patients can be safely fast
      tracked with high satisfaction and outstanding results.

PMID- 18831508
TI  - Uniportal video-assisted thoracic surgery for diagnosis and treatment of
      intrathoracic conditions.
AB  - The effort to reduce the invasiveness of thoracic surgery is increasing in this
      specialty. In this context, preliminary evidence has shown that uniportal video
      assisted thoracic surgery represents a valuable option to perform different
      diagnostic and curative procedures. This article addresses the topic of uniportal
      video-assisted thoracic surgery as the least invasive such approach that may be
      used to diagnose and treat several intrathoracic conditions.

PMID- 18831509
TI  - Awake operative videothoracoscopic pulmonary resections.
AB  - The authors' initial experience with awake videothoracoscopic lung resection
      suggests that these procedures can be easily and safely performed under sole
      thoracic epidural anesthesia with no mortality and negligible morbidity. One
      major concern was that operating on a ventilating lung would render surgical
      maneuvers more difficult because of the lung movements and lack of a sufficient
      operating space. Instead, the open pneumothorax created after trocar insertion
      produces a satisfactory lung collapse that does not hamper surgical maneuvers.
      These results contradict the accepted assumption that the main prerequisite for
      allowing successful thoracoscopic lung surgery is general anesthesia with one
      lung ventilation. No particular training is necessary to accomplish an awake
      pulmonary resection for teams experienced in thoracoscopic surgery, and
      conversions to general anesthesia are mainly caused by the presence of extensive
      fibrous pleural adhesions or the development of intractable panic attacks.
      Overall, awake pulmonary resection is easily accepted and well tolerated by
      patients, as confirmed by the high anesthesia satisfaction score, which was
      better than in nonawake control patients. Nonetheless, thoracic epidural
      anesthesia has potential complications, including epidural hematoma, spinal cord
      injury, and phrenic nerve palsy caused by inadvertently high anesthetic level,
      but these never occurred in the authors' experience. Further concerns relate to
      patient participation in operating room conversations or risk for development of
      perioperative panic attacks. However, the authors have found that reassuring the
      patient during the procedure, explaining step-by-step what is being performed,
      and even showing the ongoing procedure on the operating video can greatly improve
      the perioperative wellness and expectations of patients, particularly if the
      procedure is performed for oncologic diseases. Panic attacks occurred in few
      patients and could be usually managed through moderately increasing the depth of
      sedation while maintaining spontaneous breathing. Finally, as long as the
      physiologic impact of awake metastasectomy is definitively elucidated, the
      authors believe this modality should be used for unilateral procedures, while
      deserving a staged bilateral approach for bilateral lung metastasectomy.
      Avoidance of general anesthesia results in a faster recovery with immediate
      return to many daily life activities, including drinking, eating, and walking,
      and a reduction in hospital stay and procedure-related costs. If confirmed with
      future studies, these results could advocate earlier resection of peripheral
      solitary pulmonary nodules, reducing the risk for delaying a diagnosis of
      unexpected pulmonary malignancy. Furthermore, potential new frontiers of awake
      thoracoscopic surgery might include assessment of feasibility and safety of
      anatomic resections in properly selected instances. Ethical and economical
      concerns push remorselessly for less frequent and less-invasive surgery.
      Administrators advocate minimal hospitalization and cost-saving treatments,
      whereas patients ultimately ask for appropriate health care. Thoracic surgeons of
      the third millennium must accept the challenge of this dynamic and rapidly
      evolving scenario without loosing the right root, which probably lays just
      between well-established conventional surgery techniques and newly available
      advanced technology tools. Awake thoracic surgery will benefit from evidence
      based data that are progressively accumulating. Findings will stimulate experts
      to continue an active clinical investigation in this unpredictably evolving
      surgical field, which might ultimately lead to a better understanding of
      cardiorespiratory physiology and effects of the surgical pneumothorax and
      thoracic epidural anesthesia on perioperative, respiratory function in awake
      patients. As the Italian architect Renzo Piano recently stated, "Recovering in
      the past can be reassuring but the future is the only place where we can go."

PMID- 18831510
TI  - Outpatient thoracic surgery.
AB  - In summary, from the different alternatives to conventional hospitalization
      developed in the last decades, outpatient surgery has been the one with the
      greatest growth. However, only few studies have been reported on thoracic surgery
      and there is still great potential for an increase in outpatient thoracic
      surgery. The aim of this article has been to evaluate the clinical aspects,
      results, and economical impact of an outpatient thoracic surgery program (OTSP).
      Video-assisted mediastinoscopy, lung biopsy, and bilateral thoracic sympathectomy
      can be accomplished safely in a significant percentage of cases as ambulatory
      patients. The impact of the economical benefit of outpatient thoracic surgical
      program over the conventional hospitalization depends on the previous
      department's policy on hospital stay. Further experience is needed to increase
      the substitution index and expand the OTSP to other procedures.

PMID- 18831511
TI  - Expression of the embryonic lethal abnormal vision-like protein HuR in human
      mesothelioma: association with cyclooxygenase-2 and prognosis.
AB  - BACKGROUND: The human embryonic lethal abnormal vision (ELAV)-like protein HuR is
      a messenger RNA (mRNA)-binding protein that controls the stability of certain
      transcripts, including cyclooxygenase2 (COX-2). METHODS: To investigate a
      possible contribution of dysregulation of mRNA stability to the progression of
      cancer and to COX-2 over expression in mesothelioma, the authors studied
      expression of COX-2 and HuR in 5 mesothelioma cell lines (MSTO, NCI, Ist-Mes1,
      Ist-Mes2, and MPP89) and in a group of 29 human mesothelioma specimens that were
      characterized previously for COX-2 expression. RESULTS: All 5 cell lines
      expressed HuR, whereas COX-2 was not detectable in MSTO or NCI cells. Treatment
      with cytokines induced a shift in systolic HuR protein levels in MPP89 and Ist
      Mes2 cells that was accompanied by an increase in the expression of COX-2 mRNA
      and protein. In Ist-Mes1 cells, cytokine stimulation did not cause the passage of
      HuR from nucleus to cytoplasm, and the synthesis of COX-2 did not increase. In
      tumor tissues, immunohistochemistry revealed a positive, statistically
      significant correlation between high COX-2 expression and cytoplasmic
      localization of HuR (P = .016). Moreover, on univariate analysis, overall
      survival was found to be influenced strongly by cytoplasmic HuR localization (P =
      .004). CONCLUSIONS: The current results suggested that HuR plays a role in tumor
      progression in mesothelioma and that COX-2 may be a target of its activity in
      neoplastic cells. Together, these observations indicate that strategies aiming
      toward the modulation of HuR may have a potential clinical benefit in
      mesothelioma.

PMID- 18831512
TI  - Health care utilization by adult Hispanic long-term survivors of hematopoietic
      stem cell transplantation: report from the Bone Marrow Transplant Survivor Study.
AB  - BACKGROUND: Long-term hematopoietic cell transplantation (HCT) survivors have a
      high prevalence of severe and chronic health conditions, placing significant
      demands on the healthcare system. The objective of the current study was to
      evaluate and compare the healthcare utilization by adult Hispanic and non
      Hispanic white long-term survivors of HCT. METHODS: A mailed questionnaire was
      used to assess self-reported healthcare utilization in 3 domains: general contact
      with healthcare system, general physical examination outside cancer center (GPE),
      and cancer/HCT center visit. Eligible individuals had undergone HCT between 1974
      and 1998, at age > or =21 years, and had survived > or =2 years after HCT.
      RESULTS: The cohort included 681 non-Hispanic white and 137 Hispanic survivors.
      The median age at HCT was 38.3 years, and the median length of follow-up was 6.6
      years. Hispanic survivors had lower family income and education and were more
      likely to lack health insurance. The prevalence of GPE increased significantly
      over time among non-Hispanic whites (67% at 2-5 years to 76% at 11+ years) but
      remained unchanged among Hispanics (66% to 61%). Cancer/HCT center visits
      declined over time among both Hispanics and non-Hispanic whites, but a higher
      proportion of Hispanics reported cancer/HCT center visits at 11+ years after HCT
      (81% vs 54%). CONCLUSIONS: Compared with non-Hispanic whites, Hispanic survivors
      are less likely to establish contact with primary care providers years after HCT
      and to continue to receive care at cancer/HCT centers. Future studies of this
      population are needed to establish the factors responsible for this pattern of
      healthcare utilization.

PMID- 18831513
TI  - Head and neck squamous cell carcinoma in 13 patients with Fanconi anemia after
      hematopoietic stem cell transplantation.
AB  - BACKGROUND: Fanconi anemia (FA) is a chromosomal instability disorder with a very
      high risk of developing head and neck squamous cell carcinoma (HNSCC), most
      notably after hematopoietic stem cell transplantation (HSCT). METHODS: In the
      current study, the authors reported 13 cases of HNSCC in FA patients who
      underwent HSCT at the Saint Louis Hospital between 1976 and 2007. RESULTS: The
      median age of the patients at time of HSCT was 9.7 years. All patients received
      irradiation-based conditioning before HSCT and all developed extensive chronic
      graft versus host disease (GVHD). HNSCC was diagnosed at a median interval of 10
      years after HSCT, mainly in numerous sites within the oral cavity (11 patients).
      Lymph node involvement was diagnosed in 4 patients. The TNM classification was:
      T1 in 6 patients, T2 in 2 patients, T3 in 2 patients, and T4 in 3 patients.
      Treatment was comprised of surgery in 10 patients, with clear surgical margins
      reported in 7 (including cervical lymph node dissection in 6 patients). Surgery
      was performed in addition to other treatments in only 2 patients (radiotherapy or
      cryotherapy). For the remaining 3 patients, treatment consisted in radiotherapy
      (2 patients) or chemotherapy (1 patient). Disease progression while receiving
      therapy was observed in 5 patients and 5 other patients developed disease
      recurrence between 3.5 and 23.7 months after treatment. Death occurred in 11
      patients. At the time of last follow-up, only 2 patients were alive without any
      disease between 9 and 23 months after diagnosis. CONCLUSIONS: HNSCC developing in
      FA patients after HSCT is associated with a very poor prognosis. A systematic
      surveillance of the oral cavity is essential to permit early surgery, which to
      the authors' knowledge remains the only curative treatment for a minority of
      patients. It is very important to attempt to prevent this cancer by reducing
      chronic GVHD and using conditioning without irradiation.

PMID- 18831514
TI  - Association of PTEN gene methylation with genetic alterations in the
      phosphatidylinositol 3-kinase/AKT signaling pathway in thyroid tumors.
AB  - BACKGROUND: The phosphatidylinositol 3-kinase (PI3K)/AKT pathway plays an
      important role in thyroid tumorigenesis and progression. Genetic alterations,
      particularly PIK3CA amplification and mutations and ras mutations, are the major
      cause of aberrant activation of this pathway in thyroid tumors. Epigenetic
      silencing of the PTEN gene, a negative regulator of the PI3K/AKT pathway, also
      occurs in thyroid tumors, but its relationship with genetic alterations in this
      pathway is unclear. METHODS: By using quantitative methylation-specific
      polymerase chain reaction, the authors examined PTEN methylation and its
      relationship with genetic alterations in the PI3K/AKT pathway in various types of
      thyroid tumors. RESULTS: The authors found PTEN methylation to become
      progressively higher from benign thyroid adenoma to follicular thyroid cancer and
      to aggressive anaplastic thyroid cancer, which harbored activating genetic
      alterations in the PI3K/AKT pathway correspondingly with a progressively higher
      prevalence. The association of PTEN methylation was seen with both overall
      genetic alterations and individual genetic alterations, particularly PIK3CA
      alterations and ras mutations, in the PI3K/AKT pathway within each of the 3 types
      of thyroid tumors. In contrast, no such relationship was observed for the tumor
      suppressor gene RASSF1A. CONCLUSIONS: The authors found an interesting
      association of PTEN methylation with the activating genetic alterations in the
      PI3K/AKT pathway in thyroid tumors. This finding is consistent with a model in
      which aberrant methylation and hence silencing of the PTEN gene, which coexists
      with activating genetic alterations of the PI3K/AKT pathway, may enhance the
      signaling of this pathway aberrantly activated by genetic alterations and hence
      contribute to the progression of thyroid tumors. Cancer 2008.

PMID- 18831516
TI  - Effecting science, affecting medicine: homosexuality, the Kinsey reports, and the
      contested boundaries of psychopathology in the United States, 1948-1965.
AB  - Despite the well-documented intensive battle between Alfred Kinsey and American
      psychiatrists around the mid-twentieth century, this paper argues that Kinsey's
      work, in fact, played a significant role in transforming mental health experts'
      view of homosexuality starting as far back as the late 1940s and extending all
      the way through the mid-1960s. After analyzing the way in which Kinsey's work
      pushed American psychiatrists to re-evaluate their understanding of homosexuality
      indirectly through the effort of clinical psychologists, I then focus to a
      greater extent on examples that illustrate how the Kinsey reports directly
      influenced members of the psychiatric community. In the conclusion, using a
      Foucauldian conception of "discourse," I propose that in order to approach the
      struggle around the pathological status of homosexuality in the 1950s and the
      1960s, thinking in terms of a "politics of knowledge" is more promising than
      simply in terms of a "politics of diagnosis." Central to the struggle was not
      merely the matter of medical diagnosis, but larger issues regarding the
      production of knowledge at an intersection of science and medicine where the
      parameters of psychopathology were disputed in the context of mid-twentieth
      century United States.

PMID- 18831517
TI  - From the stage to the laboratory: magicians, psychologists, and the science of
      illusion.
AB  - In 1894, French psychologist Alfred Binet published an article on the psychology
      of conjuring. By observing five magicians perform in his laboratory, he was
      hoping to gain a better understanding of the psychological processes responsible
      for inducing illusions in an audience. This article focuses on the subjects of
      these experiments and their world. It attempts to explain why five men belonging
      to a profession in which secrecy was vital agreed to enter the laboratory and
      reveal their tricks. It argues that magicians saw themselves as men of science
      and that, by entering Binet's laboratory, they were responding to an opportunity
      to participate in a world to which they wished to belong.

PMID- 18831518
TI  - John Dewey and the savage mind: uniting anthropological, psychological, and
      pedagogical thought, 1894-1902.
AB  - In 1902 influential American philosopher John Dewey wrote a short essay on
      anthropolo-gists'view of the savage mind, arguing that it had had been unfairly
      dismissed as inchoate and incapable, when in fact the savage had much to teach
      scholars about the "present mind." The ideas presented in Dewey's essay were not
      only theoretical; they also served as the basis for his entire curriculum his
      famous laboratory school at the University of Chicago. Thus, the author argues
      that Dewey's pedagogical thought informed his anthropological thought, and vice
      versa.

PMID- 18831519
TI  - The Michael-Adler report (1933): criminology under the microscope.
AB  - This paper details the responses made by social scientists as well as criminal
      justice practitioners during 1932 to a study focusing on the status of
      criminology by the Bureau of Social Hygiene. These responses ultimately led to
      the publication of the controversial Crime, Law and Social Science (1933), which
      gave much-needed direction to the development of criminology. Despite the
      importance of these responses to the creation of criminological thought, only one
      (by Edwin H. Sutherland) has previously been published. Examining the responses
      of all of the individual participants in the project gives a clearer picture of
      controversies and changes which ultimately occurred as the field of criminology
      gradually became institutionalized as an academic discipline.

PMID- 18831520
TI  - A comparison of the choice of monoclonal antibodies for recovery of fetal cells
      from maternal blood using FACS for noninvasive prenatal diagnosis of
      hemoglobinopathies.
AB  - BACKGROUND: Isolation of adequate numbers of fetal cells circulating in the
      maternal circulation is the major hurdle in developing noninvasive prenatal
      diagnostic procedures. We used flow cytometry and a combination of different
      monoclonal antibodies to compare the yield and purity of the fetal nucleated red
      blood cells at different periods of gestation. METHODS: Using a Percoll
      discontinuous gradient, the fetal nucleated erythrocytes were enriched from 7 ml
      maternal blood. In 100 samples, the enriched cells were stained with CD45, anti
      fetal hemoglobin, and glycophorin A antibodies and in 30 samples they were
      stained with CD45, anti-fetal hemoglobin, and CD71 and then sorted and used for
      fetal diagnosis of hemoglobinopathies. RESULTS: Using the first set of
      antibodies, although we were able to obtain a higher percentage of fetal
      nucleated red cells (0.07% +/- 0.2%) as compared to the second set which yielded
      comparatively smaller numbers (0.025% +/- 0.03%), there was some compromise in
      purity. CONCLUSION: Using CD45, anti-fetal hemoglobin and CD71 would be preferred
      as minimizing maternal contamination is more important than yield for prenatal
      diagnosis.

PMID- 18831523
TI  - Closure of perianal fistula using adalimumab in a Crohn's disease patient naive
      to antitumor necrosis factor alpha antibodies.

PMID- 18831525
TI  - Influenza vaccinations: should they really be encouraged for IBD patients being
      treated with immunosuppressives?

PMID- 18831524
TI  - Prebiotics in chronic intestinal inflammation.
AB  - Prebiotics are nondigestible fermentable fibers that are reported to have health
      benefits for the host. Older as well as more recent studies show beneficial
      effects in experimental colitis and lately also in human inflammatory bowel
      diseases (IBD), such as Crohn's disease, ulcerative colitis, and chronic
      pouchitis. In this review we give an overview of the benefits of prebiotics in
      rodent IBD models and in IBD patients and discuss their possible protective
      mechanisms. Commensal intestinal bacteria induce and perpetuate chronic
      intestinal inflammation, whereas others are protective. However, most of the
      current medications are directed against the exaggerated proinflammatory immune
      response of the host, some of them toxic and costly. Feeding prebiotics changes
      the composition of the intestinal microflora toward more protective intestinal
      bacteria and alters systemic and mucosal immune responses of the host. Therapy
      for IBD targeting intestinal bacteria and their function is just emerging.
      Prebiotics have the promise to be relatively safe, inexpensive, and easy to
      administer. Unraveling their protective mechanisms will help to develop rational
      applications of prebiotics. However, the initial promising results with dietary
      prebiotics in preclinical trials as well as small studies in human IBD will need
      to be confirmed in large randomized controlled clinical trials.

PMID- 18831526
TI  - Date of birth in the occurrence of inflammatory bowel disease.
AB  - BACKGROUND: It has been speculated that prenatal or perinatal exposure to
      infections affects the risk for developing inflammatory bowel disease (IBD). The
      aims of the study were to investigate the seasonal and monthly variations of
      birth dates among patients with Crohn's disease (CD) and ulcerative colitis (UC).
      METHODS: The Hospital Episode Statistics (HES) comprises data of all patients
      admitted to hospitals in England. The data between April 1997 and March 2006
      served to analyze birth dates of subjects with CD and UD, using the entirety of
      patients in the HES as controls. RESULTS: Monthly birth dates were aggregated for
      the same months across consecutive birth years from January 1920 to December 1989
      to determine whether a seasonal birth pattern existed among patients with CD and
      UC. No different seasonal birth patterns were observed between IBD patients and
      controls. A second analysis of individual months of birth, year after year, found
      that rates of births among IBD patients fluctuated from month to month. These
      fluctuations were different for CD and UC, with an overall weak correlation of r
      = 0.078, P = 0.018. There was a slight trend for stronger correlations to occur
      during more recent decades of birth, with r = 0.237 (P = 0.009) and r = 0.168 (P
      = 0.067) for the last 2 decades 1970-1979 and 1980-1989, respectively.
      CONCLUSIONS: The patterns of birth dates among IBD patients do not support the
      contention that seasonally or monthly varying environmental factors during early
      childhood shape the subsequent risk of developing IBD.

PMID- 18831527
TI  - Downregulation of glial glutamate transporters after dopamine denervation in the
      striatum of 6-hydroxydopamine-lesioned rats.
AB  - Overactivity of glutamatergic neurotransmission in the basal ganglia is known to
      be closely related to the onset and pathogenesis of Parkinson's disease.
      Glutamate homeostasis around glutamatergic synapses is tightly regulated by two
      groups of glutamate transporters: glial glutamate transporters GLT1 (EAAT2) and
      GLAST (EAAT1), and neuronal glutamate transporter EAAC1. In order to investigate
      the changes of glutamate transporters after the onset of Parkinson's disease,
      unilateral 6-hydroxydopamine-lesioned rat, an animal model of Parkinson's
      disease, was employed. By immunofluorescence and Western blot analyses, GLT1 and
      GLAST proteins were significantly reduced in the striatum with lesion. No change
      in GLT1 and GLAST protein was found in the substantia nigra. The reduction of
      GLT1 protein in the striatum was more prominent than that of GLAST protein
      (approximately 40% vs. 20%). In addition, EAAC1 protein was found to be increased
      in the substantia nigra pars reticulata of the lesioned rats but not in the
      striatum. The present results indicate that reductions of GLT1 and GLAST may
      impair glutamate homeostasis around glutamatergic synapses in the striatum and
      contribute to over-spills of glutamate in the system. An increase in the EAAC1
      level in the substantia nigra pars reticulata may increase GABA synthesis and
      enhance GABAergic neurotransmission. These results indicate that there are
      differential and distinct modulations of glutamate transporters after dopamine
      denervation in the 6-hydroxydopamine-lesioned rat.

PMID- 18831528
TI  - Neurochemical characterization of sea lamprey taste buds and afferent gustatory
      fibers: presence of serotonin, calretinin, and CGRP immunoreactivity in taste bud
      bi-ciliated cells of the earliest vertebrates.
AB  - Neuroactive substances such as serotonin and other monoamines have been suggested
      to be involved in the transmission of gustatory signals from taste bud cells to
      afferent fibers. Lampreys are the earliest vertebrates that possess taste buds,
      although these differ in structure from taste buds in jawed vertebrates, and
      their neurochemistry remains unknown. We used immunofluorescence methods with
      antibodies raised against serotonin, tyrosine hydroxylase (TH), gamma
      aminobutyric acid (GABA), glutamate, calcitonin gene-related peptide (CGRP),
      neuropeptide Y (NPY), calretinin, and acetylated alpha-tubulin to characterize
      the neurochemistry and innervation of taste buds in the sea lamprey, Petromyzon
      marinus L. For localization of proliferative cells in taste buds we used
      bromodeoxyuridine labeling and proliferating cell nuclear antigen
      immunohistochemistry. Results with both markers indicate that proliferating cells
      are restricted to a few basal cells and that almost all cells in taste buds are
      nonproliferating. A large number of serotonin-, calretinin-, and CGRP
      immunoreactive bi-ciliated cells were revealed in lamprey taste buds. This
      suggests that serotonin participates in the transmission of gustatory signals and
      indicates that this substance appeared early on in vertebrate evolution. The
      basal surface of the bi-ciliated taste bud cells was contacted by tubulin
      immunoreactive fibers. Some of the fibers surrounding the taste bud were
      calretinin immunoreactive. Lamprey taste bud cells or afferent fibers did not
      exhibit TH, GABA, glutamate, or NPY immunoreactivity, which suggests that
      expression of these substances evolved in taste buds of some gnathostomes lines
      after the separation of gnathostomes and lampreys.

PMID- 18831529
TI  - Expression of rat uterine serine proteinases homologous to mouse implantation
      serine proteinase 2.
AB  - Implantation serine protease (ISP) was first identified in the uteri of pregnant
      mice. It is thought that ISP may have an important role in the initiation of
      implantation. However, the expression status and detailed functions of ISP remain
      unclear. In this study, the expression of ISP was investigated in the rat uterus.
      The analysis of two rat genes registered in GenBank, accession nos. XM_220240 and
      XM_577076, exhibited high identities to the mouse ISP2 genes, respectively at an
      mRNA level. We labeled the former as rISP2a and the latter as rISP2b. Using RT
      PCR, we found that both genes were expressed in the uterus. Specifically, rISP2a
      mRNA was detected in the uterus throughout pregnancy, whereas rISP2b mRNA was
      only expressed in the uterus from day 5 of pregnancy until the end of gestation.
      Expression of both genes was observed specifically within the endometrial gland
      epithelium. Furthermore, rISP2a was also observed to be expressed in the fetus
      and placenta, whereas rISP2b expression was observed in the fetus but not in the
      placenta. An expressional signal of the rISP2a gene was observed in the
      spongiotrophoblasts, giant cells and decidual endometrium in the placenta. In the
      embryo, the ventral specific region was positive in rISP2a and rISP2b gene
      expression. These findings indicate the possibility that the presently examined
      genes with high identity to mouse ISP2 may play some role not only during the
      implantation phase, but also in the development of the placenta and embryo.

PMID- 18831530
TI  - Study of istradefylline in patients with Parkinson's disease on levodopa with
      motor fluctuations.
AB  - The objective of this study was to evaluate the efficacy, safety, and
      tolerability of istradefylline 20 mg once daily versus placebo as an adjunct to
      levodopa in subjects with Parkinson's disease (PD) who have motor fluctuations.
      Istradefylline (KW-6002) is an adenosine A(2A) receptor antagonist that in
      primate models of PD improves motor function without causing or worsening
      dyskinesia. This 12-week, multicenter, double-blind, placebo-controlled,
      randomized, Phase 3 study of istradefylline was conducted in subjects
      experiencing an average daily OFF time of at least 3 hours (116 randomized to
      istradefylline; 115 to placebo). All were on stable levodopa regimens; 90% were
      also on stable regimens of other anti-Parkinson's medications. Istradefylline
      treated subjects had significant placebo-corrected reductions in daily OFF time
      from baseline to endpoint: 4.6% (P = 0.03) and 0.7 hours (P = 0.03). For ON time
      with troublesome dyskinesia, the changes between istradefylline and placebo were
      not significant. Istradefylline was well tolerated, with 6 (5.2%) istradefylline
      treated and 7 (6.1%) placebo-treated subjects withdrawing from the study because
      of adverse events. Dyskinesia, lightheadedness, tremor, constipation, and weight
      decrease were reported more often with istradefylline than placebo. We conclude
      that istradefylline is well tolerated and significantly reduces OFF time as an
      adjunct to levodopa in PD subjects with motor fluctuations.

PMID- 18831531
TI  - Unawareness of head tremor in essential tremor: a study of three samples of
      essential tremor patients.

PMID- 18831532
TI  - Psychogenic tremor: long-term prognosis in patients with electrophysiologically
      confirmed disease.
AB  - We describe the presenting features and long-term outcomes of patients with
      electrophysiologically-confirmed psychogenic tremor. Clinical information for all
      patients with psychogenic tremor confirmed by our Movement Disorders
      Neurophysiology Laboratory (2003-2004) was reviewed. A follow-up questionnaire
      was administered to all included patients in 2007. Psychogenic tremor was
      documented in 62 patients; 33 responded to the questionnaire (53%). Median onset
      age was 50 years (range, 15-71); 23 were female (70%). Clinical certainty of
      psychogenic etiology was: definite, 8 (24%); probable, 16 (49%), and possible, 9
      (27%). Characteristic electrodiagnostic features of psychogenic tremor were
      documented in all. All but two patients were ultimately given a definite
      diagnosis of psychogenic tremor; recommended psychiatric consultation was only
      done by 12 (36%). Twenty-one patients (64%) rated tremor disability as moderate
      or severe after a median follow-up of 5.1 years (range, 3.3-19). Improvement
      occurred spontaneously in 5 (15%), and after a specific intervention in 4 (12%),
      whereas 3 (9%) had mild but unchanged symptoms. The mean duration of symptoms,
      prior to diagnosis with psychogenic tremor, was significantly shorter for
      patients with mild or no tremor at follow-up (P = 0.037). Physiologically
      confirmed psychogenic tremor carries a poor prognosis, with unremitting or worse
      tremor persisting 3-years after diagnosis in most.

PMID- 18831533
TI  - Autonomic dysregulation in young girls with Rett Syndrome during nighttime in
      home recordings.
AB  - This study was designed to specifically characterize the autonomic phenotype of
      cardiorespiratory dysregulation during the nighttime in young girls with MECP2
      mutation-confirmed Rett Syndrome (RS), studied in their home environment.
      Computerized breath-to-breath and beat-to-beat characterization of at-home
      continuously recorded respiratory inductance plethysmography of chest/abdomen and
      ECG (VivoMetrics, Inc.) was obtained during overnight recordings in 47 girls with
      MECP2 mutation-confirmed RS and 47 age-, gender-, and ethnicity-matched screened
      controls (ages 2-7 years). We determined that although the breathing and heart
      rate appear more regular during the night compared to the day, young girls with
      RS demonstrate apparent nocturnal irregularities. Comparing daytime versus
      nighttime, breathing was more irregular, with an increased breathing frequency
      (and irregularity), mean amplitude of respiratory inductance plethysmography sum
      (AMP)/T(I), and heart rate and decreased AMP in girls with RS. Comparing girls
      with RS versus controls during nighttime recording, breathing was more irregular,
      with an increased breathing frequency (and irregularity), mean AMP/T(I), and
      heart rate. An increased uncoupling between measures of breathing and heart rate
      control indicates malregulation in the autonomic nervous system, and is apparent
      during the day as well as the night. This uncoupling may represent a mechanism
      that renders the girls with RS more vulnerable to sudden death.

PMID- 18831534
TI  - Circular dichroism and magnetic circular dichroism studies of the biferrous site
      of the class Ib ribonucleotide reductase from Bacillus cereus: comparison to the
      class Ia enzymes.
AB  - The rate limiting step in DNA biosynthesis is the reduction of ribonucleotides to
      form the corresponding deoxyribonucleotides. This reaction is catalyzed by
      ribonucleotide reductases (RNRs) and is an attractive target against rapidly
      proliferating pathogens. Class I RNRs are binuclear non-heme iron enzymes and can
      be further divided into subclasses. Class Ia is found in many organisms,
      including humans, while class Ib has only been found in bacteria, notably some
      pathogens. Both Bacillus anthracis and Bacillus cereus encode class Ib RNRs with
      over 98% sequence identity. The geometric and electronic structure of the B.
      cereus diiron containing subunit (R2F) has been characterized by a combination of
      circular dichroism, magnetic circular dichroism (MCD) and variable temperature
      variable field MCD and is compared to class Ia RNRs. While crystallography has
      given several possible descriptions for the class Ib RNR biferrous site, the
      spectroscopically defined active site contains a 4-coordinate and a 5-coordinate
      Fe(II), weakly antiferromagnetically coupled via mu-1,3-carboxylate bridges.
      Class Ia biferrous sites are also antiferromagnetically coupled 4-coordinate and
      5-coordinate Fe(II), however quantitatively differ from class Ib in bridging
      carboxylate conformation and tyrosine radical positioning relative to the diiron
      site. Additionally, the iron binding affinity in B. cereus RNR R2F is greater
      than class Ia RNR and provides the pathogen with a competitive advantage relative
      to host in physiological, iron-limited environments. These structural differences
      have potential for the development of selective drugs.

PMID- 18831536
TI  - Coarse-grained molecular dynamics simulations of the energetics of helix
      insertion into a lipid bilayer.
AB  - Experimental and computational studies have indicated that hydrophobicity plays a
      key role in driving the insertion of transmembrane alpha-helices into lipid
      bilayers. Molecular dynamics simulations allow exploration of the nature of the
      interactions of transmembrane alpha-helices with their lipid bilayer environment.
      In particular, coarse-grained simulations have considerable potential for
      studying many aspects of membrane proteins, ranging from their self-assembly to
      the relation between their structure and function. However, there is a need to
      evaluate the accuracy of coarse-grained estimates of the energetics of
      transmembrane helix insertion. Here, three levels of complexity of model system
      have been explored to enable such an evaluation. First, calculated free energies
      of partitioning of amino acid side chains between water and alkane yielded an
      excellent correlation with experiment. Second, free energy profiles for transfer
      of amino acid side chains along the normal to a phosphatidylcholine bilayer were
      in good agreement with experimental and atomistic simulation studies. Third,
      estimation of the free energy profile for transfer of an arginine residue,
      embedded within a hydrophobic alpha-helix, to the center of a lipid bilayer gave
      a barrier of approximately 15 kT. Hence, there is a substantial barrier to
      membrane insertion for charged amino acids, but the coarse-grained model still
      underestimates the corresponding free energy estimate (approximately 29 kT) from
      atomistic simulations (Dorairaj, S., and Allen, T. W. (2007) Proc. Natl. Acad.
      Sci. U.S.A. 104, 4943-4948). Coarse-grained simulations were then used to predict
      the free energy profile for transfer of a simple model transmembrane alpha-helix
      (WALP23) across a lipid bilayer. The results indicated that a transmembrane
      orientation was favored by about -70 kT.

PMID- 18831535
TI  - Covalent binding of flavins to RnfG and RnfD in the Rnf complex from Vibrio
      cholerae.
AB  - Enzymes of the Rnf family are believed to be bacterial redox-driven ion pumps,
      coupling an oxidoreduction process to the translocation of Na+ across the cell
      membrane. Here we show for the first time that Rnf is a flavoprotein, with FMN
      covalently bound to threonine-175 in RnfG and a second flavin bound to threonine
      187 in RnfD. Rnf subunits D and G are homologous to subunits B and C of Na+-NQR,
      respectively. Each of these Na+-NQR subunits includes a conserved S(T)GAT motif,
      with FMN covalently bound to the final threonine. RnfD and RnfG both contain the
      same motif, suggesting that they bind flavins in a similar way. In order to
      investigate this, the genes for RnfD and RnfG from Vibrio cholerae were cloned
      and expressed individually in that organism. In both cases the produced protein
      fluoresced under UV illumination on an SDS gel, further indicating the presence
      of flavin. However, analysis of the mutants RnfG-T175L, RnfD-T278L, and RnfD
      T187V showed that RnfG-T175 and RnfD-T187 are the likely flavin ligands. This
      indicates that, in the case of RnfD, the flavin is bound, not to the SGAT
      sequence but to the final residues of a TMAT sequence, a novel variant of the
      flavin binding motif. In the case of RnfG, flavin analysis, followed by MALDI-TOF
      TOF mass spectrometry, showed that an FMN is covalently attached to threonine
      175, the final threonine of the S(T)GAT sequence. Studies by visible, EPR, and
      ENDOR spectroscopy showed that, upon partial reduction, the isolated RnfG
      produces a neutral semiquinone intermediate. The semiquinone species disappeared
      upon full reduction and was not observed in the denatured protein. A topological
      analysis combining reporter protein fusion and computer predictions indicated
      that the flavins in RnfG and RnfD are localized in the periplasmic space. In
      contrast, in NqrC and NqrB the flavins are located in a cytoplasmic loop. This
      topological analysis suggests that there may be mechanistic differences between
      the Rnf and Na+-NQR complexes.

PMID- 18831537
TI  - Allosteric transitions in cytochrome P450eryF explored with pressure-perturbation
      spectroscopy, lifetime FRET, and a novel fluorescent substrate, Fluorol-7GA.
AB  - To establish a direct method for monitoring substrate binding in cytochrome
      P450eryF applicable at elevated hydrostatic pressures, we introduce a laser dye
      Fluorol-7GA (F7GA) as a novel fluorescent ligand. The high intensity of
      fluorescence and the reasonable resolution of the excitation band from the
      absorbance bands of P450 allowed us to establish highly sensitive binding assays
      compatible with pressure perturbation. The interactions of F7GA with P450eryF
      cause an ample spin shift revealing cooperative binding ( S50 = 8.2 +/- 1.3
      microM; n = 2.3 +/- 0.1). Fluorescence resonance energy transfer (FRET)
      experiments suggest the presence of at least two substrate binding sites with
      apparent K D values in the ranges of 0.1-0.3 and 6-9 microM. Similar to that
      observed earlier with CYP3A4, increasing hydrostatic pressure does not cause
      either a complete dissociation of the substrate complexes or a displacement of
      the spin equilibrium toward the low-spin state. Rather, increased pressure
      enhances the cooperativity of the F7GA-induced spin shift, so that the Hill
      coefficient approaches 3 at 2 kbar. Lifetime FRET experiments revealed an
      important increase in the affinity of the enzyme for F7GA at elevated pressures,
      suggesting that the binding of the ligand induces a conformational transition
      associated with an important increase in the level of protein hydration. This
      transition largely attenuates the solvent accessibility of the heme pocket and
      causes an unusual stability of the high-spin, substrate-bound enzyme at elevated
      pressures.

PMID- 18831538
TI  - Conformational flexibility of the N-terminal domain of apolipoprotein a-I bound
      to spherical lipid particles.
AB  - Lipid binding of human apolipoprotein A-I (apoA-I) occurs initially through the C
      terminal alpha-helices followed by conformational reorganization of the N
      terminal helix bundle. This led us to hypothesize that apoA-I has multiple lipid
      bound conformations, in which the N-terminal helix bundle adopts either open or
      closed conformations anchored by the C-terminal domain. To investigate such
      possible conformations of apoA-I at the surface of a spherical lipid particle,
      site-specific labeling of the N- and C-terminal helices in apoA-I by N-(1
      pyrene)maleimide was employed after substitution of a Cys residue for Val-53 or
      Phe-229. Neither mutagenesis nor the pyrene labeling caused discernible changes
      in the lipid-free structure and lipid interaction of apoA-I. Taking advantage of
      a significant increase in fluorescence when a pyrene-labeled helix is in contact
      with the lipid surface, we monitored the behaviors of the N- and C-terminal
      helices upon binding of apoA-I to egg PC small unilamellar vesicles. Comparison
      of the binding isotherms for pyrene-labeled apoA-I as well as a C-terminal
      helical peptide suggests that an increase in surface concentration of apoA-I
      causes dissociation of the N-terminal helix from the surface leaving the C
      terminal helix attached. Consistent with this, isothermal titration calorimetry
      measurements showed that the enthalpy of apoA-I binding to the lipid surface
      under near saturated conditions is much less exothermic than that for binding at
      a low surface concentration, indicating the N-terminal helix bundle is out of
      contact with lipid at high apoA-I surface concentrations. Interestingly, the
      presence of cholesterol significantly induces the open conformation of the helix
      bundle. These results provide insight into the multiple lipid-bound conformations
      that the N-terminal helix bundle of apoA-I can adopt on a lipid or lipoprotein
      particle, depending upon the availability of space on the surface and the surface
      composition.

PMID- 18831540
TI  - Signal amplification between Gbetagamma release and PI3Kgamma-mediated
      PI(3,4,5)P3 formation monitored by a fluorescent Gbetagamma biosensor protein and
      repetitive two component total internal reflection/fluorescence redistribution
      after photobleaching analysis.
AB  - Phosphoinositide 3-kinase gamma (PI3Kgamma) is activated by Gbetagamma release
      after stimulation of Galpha i -coupled receptors, involving a recruitment of the
      enzyme to the plasma membrane via interaction of the regulatory subunit p101 or
      p87 with Gbetagamma. The receptor-mediated release of Gbetagamma was, however,
      insufficient to elicit a translocation of p101 observable by classical
      fluorescence microscopy approaches. Since the mobilities of plasma membrane
      associated and cytosolic proteins differ strongly, small changes in the amount of
      plasma membrane association should be detectable by an altered diffusional
      behavior. Here, changes in mobility were monitored by fluorescence redistribution
      after photobleaching (FRAP) which was repetitively applied before and after
      stimulation of cells. To combine the advantages of total internal reflection
      (TIR) illumination, which preferentially excites fluorophors located at or near
      the plasma membrane, with that provided by the mobility information, we developed
      a combined TIR/FRAP setup which enabled us to point bleach parts of an image that
      was observed under TIR illumination. For FRAP data analysis, we introduce a
      convolution-based method and a global two component model. Using this TIR/FRAP
      approach, an increased plasma membrane association of the fluorescent Gbetagamma
      binding domain of p101 after Gbetagamma release by G protein-coupled receptor
      stimulation could be detected and quantified. By comparing the translocation
      efficiency of this domain with that of YFP-GRP1(PH), a biosensor for the
      PI3Kgamma product PI(3,4,5)P3, we evaluate the signal amplification between
      Gbetagamma release and PI(3,4,5)P3 formation after activation of Galpha i 
      coupled receptors.

PMID- 18831541
TI  - On the electronic structure and chemical bonding in the tantalum trimer cluster.
AB  - The electronic structure and chemical bonding in the Ta 3 (-) cluster are
      investigated using photoelectron spectroscopy and density functional theory
      calculations. Photoelectron spectra are obtained for Ta 3 (-) at four photon
      energies: 532, 355, 266, and 193 nm. While congested spectra are observed at high
      electron binding energies, several low-lying electronic transitions are well
      resolved and compared with the theoretical calculations. The electron affinity of
      Ta 3 is determined to be 1.35 +/- 0.03 eV. Extensive density functional
      calculations are performed at the B3LYP/Stuttgart +2f1g level to locate the
      ground-state and low-lying isomers for Ta 3 and Ta 3 (-). The ground-state for
      the Ta 3 (-) anion is shown to be a quintet ( (5)A 1') with D 3 h symmetry,
      whereas two nearly isoenergetic states, C 2 v ( (4)A 1) and D 3 h ( (6)A 1'), are
      found to compete for the ground-state for neutral Ta 3. A detailed molecular
      orbital analysis is performed to elucidate the chemical boding in Ta 3 (-), which
      is found to possess multiple d-orbital aromaticity, commensurate with its highly
      symmetric D 3 h structure.

PMID- 18831539
TI  - Spin trapping investigation of peroxide- and isoniazid-induced radicals in
      Mycobacterium tuberculosis catalase-peroxidase.
AB  - A new approach, the immuno-spin trapping assay, used a novel rabbit polyclonal
      anti-DMPO (5,5-dimethyl-1-pyrroline N-oxide) antiserum to detect protein radical
      derived DMPO nitrone adducts in the hemoprotein Mycobacterium tuberculosis
      catalase-peroxidase (KatG). This work demonstrates that the formation of protein
      nitrone adducts is dependent on the concentrations of tert-BuOOH and DMPO as
      shown by Western blotting and an enzyme-linked immunosorbent assay (ELISA). We
      have also detected protein-protein cross-links formed during turnover of Mtb KatG
      driven by tert-butyl peroxide ( tert-BuOOH) or enzymatic generation of hydrogen
      peroxide. DMPO inhibits this dimerization due to its ability to trap the amino
      acid radicals responsible for the cross-linkage. Chemical modifications by
      tyrosine and tryptophan blockage suggest that tyrosine residues are one site of
      formation of the dimers. The presence of the tuberculosis drug isoniazid (INH)
      also prevented cross-linking as a result of its competition for the protein
      radical. Protein-DMPO nitrone adducts were also generated by a continuous flux of
      hydrogen peroxide. These findings demonstrated that the protein-based radicals
      were formed not only during Mtb KatG turnover with alkyl peroxides but also in
      the presence of hydrogen peroxide. Furthermore, the formation of protein-DMPO
      nitrone adducts was accelerated in the presence of isoniazid.

PMID- 18831542
TI  - A quantum chemical study of the generation of a potential prebiotic compound,
      cyanoacetaldehyde, and related sulfur containing species.
AB  - Cyanoacetaldehyde (NCCH 2CHO), which may have played a role in the prebiotic
      formation of the pyrimidine bases cytosine and uracil, is formed in water
      solutions by addition of water to cyanoacetylene (HCC-CN), a compound that exists
      in interstellar space, in comets, and planetary atmospheres. A gas-phase model of
      the uncatalyzed addition of water to cyanoacetylene is explored by ab initio
      calculations at the MP2/6-311++G** level of theory. A reaction path consisting of
      several steps was found in these calculations, but the activation energy of the
      first step is relatively high, which makes it unlikely that cyanoacetaldehyde is
      formed in an uncatalyzed reaction. Similar calculations were also performed for
      the uncatalyzed reaction of water to protonated cyanoacetylene (HCCCNH (+)), a
      component of the interstellar medium, forming protonated cyanoacetaldehyde (HNCCH
      2CHO (+)), but a high activation energy was found for this reaction as well.
      Moreover, the corresponding addition reactions of hydrogen sulfide (H 2S) to
      HCCCN, as well as to HCCCNH (+), have been explored with similar results.

PMID- 18831543
TI  - Structure, vibrational spectra, and unimolecular dissociation of gaseous 1-fluoro
      1-phenethyl cations.
AB  - The multiple CF bond character of PhCFMe (+) ions has been examined by means of
      theory, vibrational spectroscopy of the gaseous ions, and unimolecular
      decomposition chemistry. Atoms in Molecules analysis of DFT wave functions gives
      a CF bond order of n = 1.25 (as compared with n = 1.38 for Me 2CF (+), relative
      to n = 1 for fluoromethane and n = 2 for diatomic CF (+)), which is consistent
      with calculations of adiabatic CF stretching frequencies (nu CF). Experimental
      gas phase IR spectra, recorded by means of resonant multiphoton dissociation
      (IRMPD) using a free-electron laser connected to an FTICR mass spectrometer, show
      good agreement with predicted band positions for five deuterated isotopomers of
      PhCFMe (+). Metastable ion decompositions of deuterated analogues of PhCFMe (+)
      show the same HF/DF loss patterns as those produced by IRMPD. The evidence
      supports the conclusion that PhCFMe ions retain structural integrity until they
      become sufficiently excited to dissociate, whereupon they undergo intramolecular
      hydrogen scrambling that is competitive with HF/DF expulsion. Relative rates of
      hydrogen transposition and unimolecular dissociation are extracted from relative
      experimental fragment ion abundances. The predominant decomposition pathway is
      inferred to operate via a five-center transition state, as opposed to a four
      center transition state for HF loss from gaseous Me 2CF (+).

PMID- 18831544
TI  - Photostability via sloped conical intersections: a computational study of the
      pyrene radical cation.
AB  - The photophysics of the pyrene radical cation, a polycyclic aromatic hydrocarbon
      (PAH) and a possible source of diffuse interstellar bands (DIBs), is investigated
      by means of hybrid molecular mechanics-valence bond (MMVB) force field and
      multiconfigurational CASSCF and CASPT2 ab initio methods. Potential energy
      surfaces of the first three electronic states D 0, D 1, and D 2 are calculated.
      MMVB geometry optimizations are carried out for the first time on a cationic
      system; the results show good agreement with CASSCF optimized structures, for
      minima and conical intersections, and errors in the energy gaps are no larger
      than those found in our previous studies of neutral systems. The presence of two
      easily accessible sloped D 1/D 2 and D 0/D 1 conical intersections suggests the
      pyrene radical cation is highly photostable, with ultrafast nonradiative decay
      back to the initial ground state geometry predicted via a mechanism similar to
      the one found in the naphthalene radical cation.

PMID- 18831545
TI  - Can descriptors of the electron density distribution help to distinguish
      functional groups?
AB  - Our study is aimed at understanding the characteristics of functional group
      descriptors based on peaks of the electronic density distribution rho(->r) . The
      descriptors calculated are the rho(->r) value at peak location, volume,
      ellipticity, curvatures of rho ( r) , and the peak-functional group distance. By
      the implementation of an automated and global process for large-scale calculation
      of the descriptors, we generated a statistically meaningful data set focusing on
      the association between peaks and 77 types of functional groups extracted from
      62,936 organic molecules issued from the Cambridge Structural Database.
      Statistical analyses demonstrated that selected descriptors are capable of
      discriminating subtypes of functional groups. A projection in a principal
      component space coupled to a hierarchical clustering confirmed the suitability of
      the descriptors to provide an appropriate description of the functional groups.
      The results indicated that functional similarity or dissimilarity could be
      quantified based on electron density descriptors.

PMID- 18831546
TI  - Studies of the mechanism of selectivity of protein tyrosine phosphatase 1B
      (PTP1B) bidentate inhibitors using molecular dynamics simulations and free energy
      calculations.
AB  - Bidentate inhibitors of protein tyrosine phosphatase 1B (PTP1B) are considered as
      a group of ideal inhibitors with high binding potential and high selectivity in
      treating type II diabetes. In this paper, the binding models of five bidentate
      inhibitors to PTP1B, TCPTP, and SHP-2 were investigated and compared by using
      molecular dynamics (MD) simulations and free energy calculations. The binding
      free energies were computed using the Molecular Mechanics/Poisson-Boltzmann
      Surface Area (MM/PBSA) methodology. The calculation results show that the
      predicted free energies of the complexes are well consistent with the
      experimental data. The Molecular Mechanics/Generalized Born Surface Area
      (MM/GBSA) free energy decomposition analysis indicates that the residues ARG24,
      ARG254, and GLN262 in the second binding site of PTP1B are essential for the high
      selectivity of inhibitors. Furthermore, the residue PHE182 close to the active
      site is also important for the selectivity and the binding affinity of the
      inhibitors. According to our analysis, it can be concluded that in most cases the
      polarity of the portion of the inhibitor that binds to the second binding site of
      the protein is positive to the affinity of the inhibitors while negative to the
      selectivity of the inhibitors. We expect that the information we obtained here
      can help to develop potential PTP1B inhibitors with more promising specificity.

PMID- 18831547
TI  - Formation of P-C bonds under unexpectedly mild conditions. Phosphoryl migration
      and metal coordination of diphenylphosphinomethyl-oxazolines and -thiazolines.
AB  - The heterocycles 2-methyl-2-oxazoline (mox) and 2-methyl-2-thiazoline (mth) react
      with Ph2PCl under mild conditions, in the presence of NEt3 which promotes their
      phosphorylation by stabilization of their enamino tautomers mox(e) and mth(e),
      respectively, and which also behaves as HCl scavenger. Depending on the reaction
      conditions, three different phosphine ligands were obtained in good yields from
      mox: the monophosphine Ph2PCH2C=NCH2CH2O (1ox) and the isomeric diphosphines
      Ph2PCH=COCH2CH2NPPh2 (2ox) (X-ray structure) and (Ph2P)2CHC=NCH2CH2O (3ox). The
      formation of these ligands involves phosphoryl migration reactions, which were
      studied by NMR spectroscopy. The synthesis and the X-ray structures of the
      corresponding diphenylphosphinothiazolines Ph2PCH2C=NCH2CH2S (1th) and
      Ph2CH=CSCH2CH2NPPh2 (2th) are also reported but the thiazoline analog of the
      geminal diphosphine 3ox was not observed. The metal complexes [Pt(3ox-H)2] x 4
      CH2Cl2 (4 x 4 CH2Cl2), [Pt(Me)I(1ox)] (5), [Pt(Me)2(1ox)] (7), [Pd(dmba
      C,N)(1th)]OTf x 0.25 Et2O (8 x 0.25 Et2O), [Pd(dmba-C,N)(1th-H)] (9), and [9 x
      {Pd(dmba-C,N)Cl}] x 2.5 C6H6 (10 x 2.5 C6H6) have been prepared and structurally
      characterized by X-ray diffraction.

PMID- 18831548
TI  - Peptide synthesis in aqueous environments: the role of extreme conditions on
      amino acid activation.
AB  - The free energy surfaces and reaction mechanisms underlying the activation of
      amino acids by COS in bulk water at ambient conditions as well as extreme
      temperature-pressure thermodynamic conditions were studied using accelerated ab
      initio molecular dynamics. The results for the reaction sequence leading from
      glycine to its activated form, a so-called Leuchs anhydride or alpha-amino acid N
      carboxyanhydride (NCA), suggest that extreme conditions not far from the critical
      point of water may favor the formation of this activated species. This is traced
      back to appropriately affecting relative stabilities of neutral versus charged or
      zwitterionic molecular species which shifts equilibria, affects relative
      barriers, and thus modifies reaction rates. Furthermore, it is shown that the N
      carboxyanhydride of glycine is not formed from N-thiocarboxyl glycine by its
      direct cyclization, but instead an indirect mechanism, the so-called isocyanate
      route, is clearly preferred at both conditions. The work quantitatively underpins
      the impact of extreme solvent conditions on the investigated organic reactions in
      aqueous media which implies that the presented results are of relevance to fields
      such as prebiotic chemistry and green chemistry.

PMID- 18831549
TI  - A global metabolite profiling approach to identify protein-metabolite
      interactions.
AB  - Understanding the biochemical functions of proteins is an important factor in
      elucidating their cellular and physiological functions. Due to the predominance
      of biopolymer interactions in biology, many methods have been designed to
      interrogate and identify biologically relevant interactions that proteins make to
      DNA, RNA, and other proteins. Complementary approaches that can elucidate binding
      interactions between proteins and small molecule metabolites will impact the
      understanding of protein-metabolite interactions and fill a need that is outside
      the scope of current methods. Here, we demonstrate the ability to identify
      natural protein-metabolite interactions from complex metabolite mixtures by
      combining a protein-mediated small molecule enrichment step with a global
      metabolite profiling platform.

PMID- 18831550
TI  - Role of the Zn1 and Zn2 sites in metallo-beta-lactamase L1.
AB  - In an effort to probe the role of the Zn(II) sites in metallo-beta-lactamase L1,
      mononuclear metal ion containing and heterobimetallic analogues of the enzyme
      were generated and characterized using kinetic and spectroscopic studies.
      Mononuclear Zn(II)-containing L1, which binds Zn(II) in the consensus Zn1 site,
      was shown to be slightly active; however, this enzyme did not stabilize a
      nitrocefin-derived reaction intermediate that had been previously detected.
      Mononuclear Co(II)- and Fe(III)-containing L1 were essentially inactive, and NMR
      and EPR studies suggest that these metal ions bind to the consensus Zn2 site in
      L1. Heterobimetallic analogues (ZnCo and ZnFe) analogues of L1 were generated,
      and stopped-flow kinetic studies revealed that these enzymes rapidly hydrolyze
      nitrocefin and that there are large amounts of the reaction intermediate formed
      during the reaction. The heterobimetallic analogues were reacted with nitrocefin,
      and the reactions were rapidly freeze quenched. EPR studies on these samples
      demonstrate that Co(II) is 5-coordinate in the resting state, proceeds through a
      4-coordinate species during the reaction, and is 5-coordinate in the enzyme
      product complex. These studies demonstrate that the metal ion in the Zn1 site is
      essential for catalysis in L1 and that the metal ion in the Zn2 site is crucial
      for stabilization of the nitrocefin-derived reaction intermediate.

PMID- 18831551
TI  - Simple host-guest chemistry to modulate the process of concentration and
      crystallization of membrane proteins by detergent capture in a microfluidic
      device.
AB  - This paper utilizes cyclodextrin-based host-guest chemistry in a microfluidic
      device to modulate the crystallization of membrane proteins and the process of
      concentration of membrane protein samples. Methyl-beta-cyclodextrin (MBCD) can
      efficiently capture a wide variety of detergents commonly used for the
      stabilization of membrane proteins by sequestering detergent monomers. Reaction
      Center (RC) from Blastochloris viridis was used here as a model system. In the
      process of concentrating membrane protein samples, MBCD was shown to break up
      free detergent micelles and prevent them from being concentrated. The addition of
      an optimal amount of MBCD to the RC sample captured loosely bound detergent from
      the protein-detergent complex and improved sample homogeneity, as characterized
      by dynamic light scattering. Using plug-based microfluidics, RC crystals were
      grown in the presence of MBCD, giving a different morphology and space group than
      crystals grown without MBCD. The crystal structure of RC crystallized in the
      presence of MBCD was consistent with the changes in packing and crystal contacts
      hypothesized for removal of loosely bound detergent. The incorporation of MBCD
      into a plug-based microfluidic crystallization method allows efficient use of
      limited membrane protein sample by reducing the amount of protein required and
      combining sparse matrix screening and optimization in one experiment. The use of
      MBCD for detergent capture can be expanded to develop cyclodextrin-derived
      molecules for fine-tuned detergent capture and thus modulate membrane protein
      crystallization in an even more controllable way.

PMID- 18831552
TI  - Silica-void-gold nanoparticles: temporally stable surface-enhanced Raman
      scattering substrates.
AB  - Reproducible detection of a target molecule is demonstrated using temporally
      stable solution-phase silica-void-gold nanoparticles and surface-enhanced Raman
      scattering (SERS). These composite nanostructures are homogeneous (diameter = 45
      +/- 4 nm) and entrap single 13 nm gold nanoparticle cores inside porous silica
      membranes which prevent electromagnetic coupling and aggregation between adjacent
      nanoparticles. The optical properties of the gold nanoparticle cores and
      structural changes of the composite nanostructures are characterized using
      extinction spectroscopy and transmission electron microscopy, respectively, and
      both techniques are used to monitor the formation of the silica membrane. The
      resulting nanostructures exhibit temporally stable optical properties in the
      presence of salt and 2-naphthalenethiol. Similar SERS spectral features are
      observed when 2-naphthalenethiol is incubated with both bare and membrane
      encapsulated gold nanoparticles. Disappearance of the S-H Raman vibrational band
      centered at 2566 cm(-1) with the composite nanoparticles indicates that the
      target molecule is binding directly to the metal surface. Furthermore, these
      nanostructures exhibit reproducible SERS signals for at least a 2 h period. This
      first demonstration of utilizing solution-phase silica-void-gold nanoparticles as
      reproducible SERS substrates will allow for future fundamental studies in
      understanding the mechanisms of SERS using solution-phase nanostructures as well
      as for applications that involve the direct and reproducible detection of
      biological and environmental molecules.

PMID- 18831554
TI  - L-selectride-mediated highly diastereoselective asymmetric reductive aldol
      reaction: access to an important subunit for bioactive molecules.
AB  - L-selectride reduction of a chiral or achiral enone followed by reaction of the
      resulting enolate with optically active alpha-alkoxy aldehydes proceeded with
      excellent diastereoselectivity. The resulting alpha,alpha-dimethyl-beta-hydroxy
      ketones are inherent to a variety of biologically active natural products.

PMID- 18831553
TI  - Substrate-promoted formation of a catalytically competent binuclear center and
      regulation of reactivity in a glycerophosphodiesterase from Enterobacter
      aerogenes.
AB  - The glycerophosphodiesterase (GpdQ) from Enterobacter aerogenes is a promiscuous
      binuclear metallohydrolase that catalyzes the hydrolysis of mono-, di-, and
      triester substrates, including some organophosphate pesticides and products of
      the degradation of nerve agents. GpdQ has attracted recent attention as a
      promising enzymatic bioremediator. Here, we have investigated the catalytic
      mechanism of this versatile enzyme using a range of techniques. An improved
      crystal structure (1.9 A resolution) illustrates the presence of (i) an extended
      hydrogen bond network in the active site, and (ii) two possible nucleophiles,
      i.e., water/hydroxide ligands, coordinated to one or both metal ions. While it is
      at present not possible to unambiguously distinguish between these two
      possibilities, a reaction mechanism is proposed whereby the terminally bound
      H2O/OH(-) acts as the nucleophile, activated via hydrogen bonding by the bridging
      water molecule. Furthermore, the presence of substrate promotes the formation of
      a catalytically competent binuclear center by significantly enhancing the binding
      affinity of one of the metal ions in the active site. Asn80 appears to display
      coordination flexibility that may modulate enzyme activity. Kinetic data suggest
      that the rate-limiting step occurs after hydrolysis, i.e., the release of the
      phosphate moiety and the concomitant dissociation of one of the metal ions and/or
      associated conformational changes. Thus, it is proposed that GpdQ employs an
      intricate regulatory mechanism for catalysis, where coordination flexibility in
      one of the two metal binding sites is essential for optimal activity.

PMID- 18831555
TI  - Iodocyclization of ethoxyethyl ethers to alkynes: a broadly applicable synthesis
      of 3-iodobenzo[b]furans.
AB  - A wide variety of 3-iodobenzo[b]furans were readily prepared by iodocyclization
      of 2-alkynyl-1-(1-ethoxyethoxy)benzenes with the I(coll)2PF6-BF3 x OEt2
      combination. Aryl-, vinylic-, and alkyl-substituted alkynes undergo
      iodocyclization in good to excellent yields. The mechanism of the reaction is
      also discussed.

PMID- 18831556
TI  - An efficient synthesis of 2,6-disubstituted benzobisoxazoles: new building blocks
      for organic semiconductors.
AB  - 2,6-Disubstituted benzobisoxazoles have been synthesized by a highly efficient
      reaction of diaminobenzene diols with various orthoesters. The scope of this new
      reaction for the synthesis of substituted benzobisoxazoles has been investigated
      using four different orthoesters. The utility of these compounds as building
      blocks for the synthesis of conjugated polymers is demonstrated.

PMID- 18831557
TI  - Ratiometric sensing of Hg2+ based on the calix[4]arene of partial cone
      conformation possessing a dansyl moiety.
AB  - A new fluorescent chemosensor based on the calix[4]arene of partial cone
      conformation possessing a dansyl moiety has been synthesized. The chemosensor
      demonstrates selective optical recognition of Hg(2+) and Cu(2+) in two
      contrasting modes. The receptor exhibited ratiometric sensing of Hg(2+) and "ON
      OFF" type of fluorescence behavior in the presence of Cu(2+). The compound
      behaves as a fluorescent molecular switch upon chemical inputs of Hg(2+) and
      Cu(2+) ions.

PMID- 18831558
TI  - Tandem aziridination/rearrangement reaction of allylic alcohols: an efficient
      approach to 2-quaternary Mannich bases.
AB  - A novel tandem aziridination/rearrangement reaction of allylic alcohols has been
      discovered, in which the significant accelerating effect of silica gel has been
      identified. On the basis of this methodology, an efficient and highly
      stereoselective approach to various 2-quaternary Mannich bases has been put in
      place, readily providing an alternative route to the conventional vicinal amino
      functionalization of alkenes.

PMID- 18831559
TI  - Structures and antioxidant activity of anthocyanins in many accessions of
      eggplant and its related species.
AB  - Anthocyanins were detected in extracts from the peels of 123 accessions of
      eggplant (Solanum melongena) and its related species. Their anthocyanin profiles
      were classified into four types, including known Japanese eggplant type (type 1)
      and non-Japanese eggplant type (type 2). Although most of the eggplant accessions
      had one of the two known profiles, one accession had a novel profile (type 3).
      Two accessions of related species showed another novel profile (type 4). The
      major anthocyanins were identified as delphinidin 3-(p-coumaroylrutinoside)-5
      glucoside (nasunin) (type 1), delphinidin 3-rutinoside (type 2), delphinidin 3
      glucoside (type 3), and petunidin 3-(p-coumaroylrutinoside)-5-glucoside
      (petunidin 3RGc5G) (type 4). Delphinidin 3-caffeoylrutinoside-5-glucoside
      (delphinidin 3RGcaf5G) was isolated from the hybrid (F1) plants of a type 1
      cultivar and a type 3 germplasm. Among the five purified anthocyanins,
      delphinidin 3RGcaf5G showed the highest radical-scavenging activities toward both
      1,1-diphenyl-2-picrylhydrazyl (DPPH) radical and linoleic acid radical, followed
      in order by nasunin and petunidin 3RGc5G.

PMID- 18831560
TI  - Effect of iron-quercetin complex on reduction of nitrite in in vitro and in vivo
      systems.
AB  - This study investigated whether reducing agents such as quercetin and iron(II)
      facilitate formation of nitric oxide (NO) gas from orally ingested nitrite in an
      vivo study. When 3 mg/kg Na (15)NO2 was orally administered to rats with or
      without iron(II) or quercetin, Hb (15)NO, which is indicative of systemic (15)NO,
      was detected in the blood, with the maximum blood concentration of Hb (15)NO at
      15 min after nitrite or nitrite plus quercetin treatment, whereas after
      administration of nitrite plus iron(II) or nitrite plus iron(II) and quercetin,
      the time was shortened to 10 min. Interestingly, iron(II), quercetin, or iron(II)
      plus quercetin did not affect the total amount of Hb (15)NO generated from orally
      administered Na (15)NO2. However, the systemic nitrite concentration was
      significantly decreased in the presence of iron(II) or iron(II) plus quercetin.
      These results may indicate that iron(II) is critical to the generation of NO gas
      from nitrite, whereas quercetin contributed little under the in vivo experimental
      conditions.

PMID- 18831561
TI  - Identification of shark species in seafood products by forensically informative
      nucleotide sequencing (FINS).
AB  - The identification of commercial shark species is a relevant issue to ensure the
      correct labeling of seafood products, to maintain consumer confidence in seafood,
      and to enhance the knowledge of the species and volumes that are at present being
      captured, thus improving the management of shark fisheries. The polymerase chain
      reaction was employed to obtain a 423 bp amplicon from the mitochondrial
      cytochrome b gene. The sequences from this fragment, belonging to 63 authentic
      individuals of 23 species, were analyzed using a genetic distance method. Nine
      different samples of commercial fresh, frozen, and convenience food were obtained
      in local and international markets to validate the methodology. These samples
      were analyzed, and sequences were employed for species identification, showing
      that forensically informative nucleotide sequencing (FINS) is a suitable
      technique for identification of processed seafood containing shark as an
      ingredient. The results also showed that incorrect labeling practices may occur
      regarding shark products, probably because of incorrect labeling at the
      production point.

PMID- 18831562
TI  - Improving the screening process for the selection of potato breeding lines with
      enhanced polyphenolics content.
AB  - Efficient selection of potato varieties with enhanced nutritional quality
      requires simple, rapid, accurate, and cost-effective assays to obtain tuber
      chemical composition information. Our objective was to develop simple protocols
      to determine phenolics, anthocyanins, and antioxidant capacity in polyphenolic
      extracts of potatoes using Fourier transform infrared spectroscopy combined with
      multivariate techniques. Lyophilized potato samples (23) were analyzed.
      Polyphenolic compounds were extracted from potatoes and applied directly applied
      onto a three-bounce ZnSe crystal for attenuated total reflectance measurements in
      the infrared region of 4000 to 700 cm (-1). Robust models were generated (r > or
      = 0.99) with standard error of cross-validation values of 4.17 mg gallic acid
      equivalent/100 g (total phenolics), 0.87 mg pelargonidin-3-glucoside/100 g
      (monomeric anthocyanins), and 130.8 mumol Trolox equivalent/100 g (antioxidant
      capacity) potato powder. In addition, classification models discriminated potato
      samples at the species and variety level. Application of a simple infrared
      spectroscopic protocol allowed simultaneous rapid quantification of specific
      nutritional components in potatoes and efficient selection of value-added potato
      varieties.

PMID- 18831563
TI  - Quantitative analyses of RAG-RSS interactions and conformations revealed by
      atomic force microscopy.
AB  - During V(D)J recombination, site specific DNA excision is dictated by the binding
      of RAG1/2 proteins to the conserved recombination signal sequence (RSS) within
      the genome. The interaction between RAG1/2 and RSS is thought to involve a large
      DNA distortion that is permissive for DNA cleavage. In this study, using atomic
      force microscopy imaging (AFM), we analyzed individual RAG-RSS complexes, in
      which the bending angle of RAG-associated RSS substrates could be visualized and
      quantified. We provided the quantitative measurement on the conformations of
      specific RAG-12RSS complexes. Previous data indicating the necessity of RAG2 for
      recombination implies a structural role in the RAG-RSS complex. Surprisingly,
      however, no significant difference was observed in conformational bending with
      AFM between RAG1-12RSS and RAG1/2-12RSS. RAG1 was found sufficient to induce DNA
      bending, and the addition of RAG2 did not change the bending profile. In
      addition, a prenicked 12RSS bound by RAG1/2 proteins displayed a conformation
      similar to the one observed with the intact 12RSS, implying that no greater DNA
      bending occurs after the nicking step in the signal complex. Taken together, the
      quantitative AFM results on the components of the recombinase emphasize a tightly
      held complex with a bend angle value near 60 degrees , which may be a
      prerequisite step for the site-specific nicking by the V(D)J recombinase.

PMID- 18831564
TI  - Sampling and electrophoretic analysis of segmented flow streams using virtual
      walls in a microfluidic device.
AB  - A method for sampling and electrophoretic analysis of aqueous plugs segmented in
      a stream of immiscible oil is described. In the method, an aqueous buffer and oil
      stream flow parallel to each other to form a stable virtual wall in a
      microfabricated K-shaped fluidic element. As aqueous sample plugs in the oil
      stream make contact with the virtual wall, coalescence occurs and sample is
      electrokinetically transferred to the aqueous stream. Using this virtual wall,
      two methods of injection for channel electrophoresis were developed. In the
      first, discrete sample zones flow past the inlet of an electrophoresis channel
      and a portion is injected by electroosmotic flow, termed the "discrete injector".
      With this approach at least 800 plugs could be injected without interruption from
      a continuous segmented stream with 5.1% RSD in peak area. This method generated
      up to 1,050 theoretical plates, although analysis of the injector suggested that
      improvements may be possible. In a second method, aqueous plugs are sampled in a
      way that allows them to form a continuous stream that is directed to a
      microfluidic cross-style injector, termed the "desegmenting injector". This
      method does not analyze each individual plug but instead allows periodic sampling
      of a high-frequency stream of plugs. Using this system at least 1000 injections
      could be performed sequentially with 5.8% RSD in peak area and 53,500 theoretical
      plates. This method was demonstrated to be useful for monitoring concentration
      changes from a sampling device with 10 s temporal resolution. Aqueous plugs in
      segmented flows have been applied to many different chemical manipulations
      including synthesis, assays, sampling processing and sampling. Nearly all such
      studies have used optical methods to analyze plug contents. This method offers a
      new way to analyze such samples and should enable new applications of segmented
      flow systems.

PMID- 18831565
TI  - Identification of covalent binding sites of phthalic anhydride in human
      hemoglobin.
AB  - Phthalic anhydride (PA) is a reactive low molecular weight compound used in the
      chemical industry. The exposure of PA may lead to work-related airway diseases
      such as rhinitis, chronic bronchitis, and asthma. The exposure gives rise to an
      increase in hapten-specific IgG antibodies in workers but with a low presence of
      specific IgE antibodies. In this study, the binding of PA to human hemoglobin
      (Hb) in vitro was investigated. Trypsin and Pronase E digestion, LC, LC/MS/MS,
      GC/MS analysis, and nanoelectrospray hybrid quadrupole time-of-flight MS were
      used to identify the adducted amino acids of the synthesized PA-Hb conjugates. In
      the conjugate with the molar ratio 1:0.1, a total of six adducted amino acids
      were identified. N-Terminal valine was found adducted in both the alpha- and the
      beta-chains as well as a total of four lysines, Val 1, Lys 16, and Lys 61 on the
      alpha-chain and Val 1, Lys 66, and Lys 144 on the beta-chain. Two types of lysine
      adducts were found, a phthalamide and a phthalimide. It was also found that PA
      differs in its binding site as compared to hexahydrophthalic anhydride. The
      result of this study suggests several interesting applications of biological
      monitoring.

PMID- 18831566
TI  - Effect of temperature on the reentrant condensation in polyelectrolyte-liposome
      complexation.
AB  - Interactions of oppositely charged macroions in aqueous solution give rise to
      intriguing aggregation phenomena, resulting in finite-size, long-lived clusters,
      characterized by a quite narrow size distribution. Particularly, the adsorption
      of highly charged linear polyelectrolytes on oppositely charged colloidal
      particles is strongly correlated and some short-range order arises from competing
      electrostatic interactions between like-charged polymer chains (repulsion) and
      between polymer chains and particle surface (attraction). In these systems, in an
      interval of concentrations around the isoelectric point, relatively large
      clusters of polyelectrolyte-decorated particles form. However, the mechanisms
      that drive the aggregation and stabilize, at the different polymer/particle
      ratios, a well-defined size of the aggregates are not completely understood. Nor
      is clear the role that the correlated polyion adsorption plays in the
      aggregation, although the importance of "patchy interactions" has been stressed
      as the possible source of attractive interaction term between colloidal
      particles. Different models have been proposed to explain the formation of the
      observed cluster phase. However, a central question still remains unanswered,
      i.e., whether the clusters are true equilibrium or metastable aggregates. To
      elucidate this point, in this work, we have investigated the effect of the
      temperature on the cluster formation. We employed liposomes built up by DOTAP
      lipids interacting with a simple anionic polyion, polyacrylate sodium salt, over
      an extended concentration range below and above the isoelectric condition. Our
      results show that the aggregation process can be described by a thermally
      activated mechanism.

PMID- 18831567
TI  - Unique cellular interaction of silver nanoparticles: size-dependent generation of
      reactive oxygen species.
AB  - The rapid advancement of nanotechnology has created a vast array of engineered
      nanomaterials (ENMs) which have unique physical (size, shape, crystallinity,
      surface charge) and chemical (surface coating, elemental composition and
      solubility) attributes. These physicochemical properties of ENMs can produce
      chemical conditions to induce a pro-oxidant environment in the cells, causing an
      imbalanced cellular energy system dependent on redox potential and thereby
      leading to adverse biological consequences, ranging from the initiation of
      inflammatory pathways through to cell death. The present study was designed to
      evaluate size-dependent cellular interactions of known biologically active silver
      nanoparticles (NPs, Ag-15 nm, Ag-30 nm, and Ag-55 nm). Alveolar macrophages
      provide the first defense and were studied for their potential role in initiating
      oxidative stress. Cell exposure produced morphologically abnormal sizes and
      adherence characteristics with significant NP uptake at high doses after 24 h.
      Toxicity evaluations using mitochondrial and cell membrane viability along with
      reactive oxygen species (ROS) were performed. After 24 h of exposure, viability
      metrics significantly decreased with increasing dose (10-75 microg/mL) of Ag-15
      nm and Ag-30 nm NPs. A more than 10-fold increase of ROS levels in cells exposed
      to 50 microg/mL Ag-15 nm suggests that the cytotoxicity of Ag-15 nm is likely to
      be mediated through oxidative stress. In addition, activation of the release of
      traditional inflammatory mediators were examined by measuring levels of
      cytokines/chemokines, including tumor necrosis factor (TNF-alpha), macrophage
      inhibitory protein (MIP-2), and interleukin-6 (IL-6), released into the culture
      media. After 24 h of exposure to Ag-15 nm nanoparticles, a significant
      inflammatory response was observed by the release of TNF-alpha, MIP-2, and IL
      1beta. However, there was no detectable level of IL-6 upon exposure to silver
      nanoparticles. In summary, a size-dependent toxicity was produced by silver
      nanoparticles, and one predominant mechanism of toxicity was found to be largely
      mediated through oxidative stress.

PMID- 18831568
TI  - Et3N-induced demethylation-annulation of 3-alkynyl-4-methoxy-2-pyridones and
      structurally related compounds in the synthesis of furan-fused heterocycles.
AB  - Various 3-iodo-4-methoxypyridin-2-ones and related pyrone and coumarin
      derivatives have been demonstrated as readily available precursors of 2
      substituted furan-fused heterocycles by means of in situ sequential Sonogashira
      acetylide coupling, dealkylation, and regioselective furan annulation reactions.
      A Et3N-induced S(N)2 process has been established that accounts for the
      dealkylation process.

PMID- 18831569
TI  - Anti-inflammatory cembranoids from the soft corals Sinularia querciformis and
      Sinularia granosa.
AB  - Four new cembranoids, querciformolides A-D (1-4), along with two known
      cembranoids, 7 and 8, have been isolated from the soft coral Sinularia
      querciformis. Furthermore, chemical investigation of Sinularia granosa has
      afforded three new cembranoids, querciformolide B (2) and granosolides A (5) and
      B (6). The structures of the new metabolites were elucidated on the basis of
      extensive spectroscopic methods, and that of 2 was further confirmed by X-ray
      diffraction analysis. The absolute configurations of 1 and 2 were determined by a
      modified Mosher's method. Among these metabolites, 2-6 are rarely found
      cembranoids possessing a tetrahydrofuran moiety with a 4,7-ether linkage; in
      addition, 1 is the first epsilon-lactone cembrane found that possesses a
      tetrahydropyran moiety with a 4,8-ether linkage. None of these compounds were
      found to be cytotoxic toward a limited panel of cancer cell lines. However,
      compounds 3, 7, and 8 significantly inhibited the accumulation of the pro
      inflammatory iNOS and COX-2 proteins in LPS-stimulated RAW264.7 macrophage cells.

PMID- 18831571
TI  - Estimating protein-ligand binding affinity using high-throughput screening by
      NMR.
AB  - Many of today's drug discovery programs use high-throughput screening methods
      that rely on quick evaluations of protein activity to rank potential chemical
      leads. By monitoring biologically relevant protein-ligand interactions, NMR can
      provide a means to validate these discovery leads and to optimize the drug
      discovery process. NMR-based screens typically use a change in chemical shift or
      line width to detect a protein-ligand interaction. However, the relatively low
      throughput of current NMR screens and their high demand on sample requirements
      generally makes it impractical to collect complete binding curves to measure the
      affinity for each compound in a large and diverse chemical library. As a result,
      NMR ligand screens are typically limited to identifying candidates that bind to a
      protein and do not give any estimate of the binding affinity. To address this
      issue, a methodology has been developed to rank binding affinities for ligands
      based on NMR screens that use 1D (1)H NMR line-broadening experiments. This
      method was demonstrated by using it to estimate the dissociation equilibrium
      constants for twelve ligands with the protein human serum albumin (HSA). The
      results were found to give good agreement with previous affinities that have been
      reported for these same ligands with HSA.

PMID- 18831572
TI  - Symmetry breaking in plasmonic nanocavities: subradiant LSPR sensing and a
      tunable Fano resonance.
AB  - A metallic nanostructure consisting of a disk inside a thin ring supports
      superradiant and very narrow subradiant modes. Symmetry breaking in this
      structure enables a coupling between plasmon modes of differing multipolar order,
      resulting in a tunable Fano resonance. The LSPR sensitivities of the subradiant
      and Fano resonances are predicted to be among the largest yet for individual
      nanostructures.

PMID- 18831570
TI  - Phosphorylated proteins and control over apatite nucleation, crystal growth, and
      inhibition.

PMID- 18831573
TI  - Chemical activation of lipoplexes formed from DNA and a redox-active, ferrocene
      containing cationic lipid.
AB  - We recently reported that the ferrocene-containing cationic lipid BFDMA [bis(11
      ferrocenylundecyl)dimethylammonium bromide] can be used to mediate cell
      transfection, and that levels of transfection depend critically upon the
      oxidation state of the ferrocenyl groups of the lipid. Here, we report that the
      redox activity of BFDMA can be exploited to transform lipoplexes formed from
      oxidized BFDMA (which do not transfect cells) to lipoplexes that are "active"
      (and thus mediate high levels of transgene expression) by treatment with the
      chemical reducing agent glutathione (GSH). We demonstrate that GSH can be used to
      reduce the ferrocenium groups of oxidized BFDMA rapidly both (i) in solution and
      (ii) in lipoplexes formed by mixing oxidized BFDMA and DNA. Lipoplexes
      transformed in this manner mediate levels of cell transfection in vitro that are
      comparable to levels of transfection mediated by lipoplexes prepared by mixing
      DNA and reduced BFDMA. We demonstrate further that the chemical reduction of
      oxidized BFDMA leads to changes in the zeta potentials of these lipoplexes (e.g.,
      from negative to positive). Characterization of lipoplex internalization using
      confocal microscopy demonstrated that these changes in zeta potential correlate
      to differences in the extents to which these lipoplexes are internalized by
      cells. These results provide a framework from which to interpret differences in
      cell transfection mediated by reduced and oxidized BFDMA. When combined, the
      results of this study suggest the basis of an approach that could be used to
      transform lipoplexes actively or "on-demand" and provide spatial and/or temporal
      control over the transfection of cells in a range of different fundamental and
      applied contexts.

PMID- 18831574
TI  - Redmond Red as a redox probe for the DNA-mediated detection of abasic sites.
AB  - Redmond Red, a fluoropore containing a redox-active phenoxazine core, has been
      explored as a new electrochemical probe for the detection of abasic sites in
      double-stranded DNA. The electrochemical behavior of Redmond Red-modified DNA at
      gold surfaces exhibits stable, quasi-reversible voltammetry with a midpoint
      potential centered around -50 mV versus NHE. Importantly, with Redmond Red
      positioned opposite an abasic site within the DNA duplex, the electrochemical
      response is significantly enhanced compared to Redmond Red positioned across from
      a base. Redmond Red, reporting only if well-stacked in the duplex, represents a
      sensitive probe to detect abasic sites electrochemically in a DNA-mediated
      reaction.

PMID- 18831575
TI  - Synthesis of peptide nucleic acid FRET probes via an orthogonally protected
      building block for post-synthetic labeling of peptide nucleic acids at the 5
      position of uracil.
AB  - We report the design and synthesis of an orthogonally protected peptide nucleic
      acid (PNA) building block, Fmoc-PNA-U'-(Dde)-OH, and its use in the construction
      of PNA FRET probes. This building block allows for the post-synthetic attachment
      of reporter groups to the amino group attached to the 5-position of uracil (U)
      following selective deprotection of the Dde group. We illustrate the use of this
      building block for the synthesis of a series of FAM Cy5 donor acceptor pairs and
      their ability to detect a target DNA sequence.

PMID- 18831576
TI  - Tetrahydrolipstatin analogues as modulators of endocannabinoid 2
      arachidonoylglycerol metabolism.
AB  - A series of 21 analogues of tetrahydrolipstatin (THL, 1) were synthesized and
      tested as inhibitors of the formation or hydrolysis of the endocannabinoid 2
      arachidonoylglycerol (2-AG). Three of the novel compounds, i.e., 11, 13, and 15,
      inhibited 2-AG formation via the diacylglycerol lipase alpha (DAGLalpha) with IC
      50 values lower than 50 nM (IC 50 of THL = 1 microM) and were between 23- and 375
      fold selective vs 2-AG hydrolysis by monoacylglycerol lipase (MAGL) as well as vs
      cannabinoid CB 1 and CB 2 receptors and anandamide hydrolysis by fatty acid amide
      hydrolase (FAAH). Three other THL analogues, i.e., 14, 16, and 18, were slightly
      more potent than THL against DAGLalpha and appreciably selective vs MAGL, CB
      receptors, and FAAH (15-26-fold). One compound, i.e., 8, was a potent inhibitor
      of MAGL-like activity (IC 50 = 0.41 microM), and relatively ( approximately 7
      fold) selective vs the other targets tested.

PMID- 18831577
TI  - Compounds of superatom clusters: preferred structures and significant nonlinear
      optical properties of the BLi6-X (X = F, LiF2, BeF3, BF4) motifs.
AB  - A new type of superalkali-(super)halogen compound, BLi6-X (X = F, LiF2, BeF3,
      BF4), is theoretically predicted. The interaction between superalkali BLi6 and
      different shaped superhalogen X is found to be strong and ionic in nature. Bond
      energies of these BLi6-X species are in the range of 151.3-220.6 kcal/mol at the
      CCSD(T)/aug-cc-pVDZ level, which are much larger than the traditional ionic bond
      energy of 130.1 kcal/mol for LiF. Furthermore, because of their delocalized
      electron character, these superalkali-(super)halogen species exhibit
      extraordinarily large first hyperpolarizabilities with beta0 ranging from 5166.5
      to 17791.0 au. Besides, the examination of the variation of nonlinear optical
      (NLO) properties with the size of (BLi6-BeF3)n assemblies shows the dependence of
      NLO properties on the chain length of (BLi6-BeF3)n. The present investigation
      gives hints to scientists in extending the research in atomic dimension to direct
      the interaction between superatoms, and using superatoms as building blocks to
      synthesize novel meaningful materials with unusual properties such as nonlinear
      optical properties.

PMID- 18831578
TI  - Aqueous uranium(VI) hydrolysis species characterized by attenuated total
      reflection Fourier-transform infrared spectroscopy.
AB  - The speciation of uranium(VI) in micromolar aqueous solutions at ambient
      atmosphere was studied by attenuated total reflection Fourier-transform infrared
      (ATR FT-IR) spectroscopy and by speciation modeling applying the updated NEA
      thermodynamic database. It can be shown that reliable infrared spectra of
      micromolar U(VI) solutions are obtained abolishing the restrictions of previous
      spectroscopic investigations to millimolar concentrations and, consequently, to
      the acidic pH range. A significant change of the U(VI) speciation can be derived
      from the spectral alterations of the absorption band representing the
      antisymmetric stretching mode (nu3) of the UO2(2+) ion observed upon lowering the
      U(VI) concentration from the milli- to the micromolar range at a constant pH 4
      value. The acquisition of spectra of diluted U(VI) solutions allows the increase
      of the pH up to 8.5 without the risk of formation of colloidal or solid phases.
      The infrared spectra are compared to the results of the computed speciation
      patterns. Although a complete interpretation of the spectra can not be given at
      this state of knowledge, the spectral data strongly suggest the presence of
      monomeric U(VI) hydroxo species already showing up at a pH value > or = 2.5 and
      dominating the speciation at pH 3. This is in contradiction to the predicted
      speciation where the fully hydrated UO2(2+) is expected to represent the main
      species at pH values below 4. At ambient pH, a more complex speciation is
      suggested compared to the results of the computational modeling technique. The
      predicted dominance of the UO2(CO3)3(4-) complex at pH > or = 8 was not confirmed
      by the infrared data. However, the infrared spectra indicate the formation of
      hydroxo complexes obviously containing carbonate ligands.

PMID- 18831579
TI  - Fluorinated beta-diketonates of the first row divalent transition metals: new
      approach to the synthesis of unsolvated species.
AB  - An original low-temperature solid-state route for the preparation of metal beta
      diketonates in their unsolvated forms has been suggested. Four new first row
      divalent transition metal beta-diketonates, M(hfac)2 (M = Mn (1), Fe (2), Co (3),
      and Ni (4); hfac = hexaluoroacetylacetonate), have been isolated in quantitative
      yield. Compounds 1-3 have been obtained by comproportionation reaction between
      the corresponding M(hfac)3 and metal powder. Ni(hfac)2 (4) has been synthesized
      by oxidation of metallic nickel with Cu(hfac)2. All products have been
      characterized spectroscopically and by X-ray powder and single crystal
      diffraction techniques. The solid state structures of 1-4 feature polynuclear
      molecules, in which the coordinatively unsaturated metal centers fulfill an
      octahedral environment by Lewis acid-base interactions with the oxygen atoms of
      diketonate ligands acting in chelating-bridging fashion. Title transition metal
      diketonates have been shown to retain their polynuclear structures upon
      sublimation-deposition procedure as well as in solutions of non-coordinating
      solvents. In coordinating solvents the molecules of 1-4 quickly form the
      mononuclear M(hfac)2L2 (L = donor solvent) complexes.

PMID- 18831580
TI  - Temperature driven reactant solubilization synthesis of BiCuOSe.
AB  - Phase-pure BiCuOSe, which is isostructural to the layered p-type transparent
      conductor LaCuOS, has been synthesized in high yield by a single-step
      hydrothermal reaction at low temperature (250 degrees C) and pressure (<20 atm).
      A moderate reaction temperature of 250 degrees C was sufficiently high to
      solubilize both Bi2O3 and Cu2O and stabilize monovalent copper and low enough to
      impede the oxidation of dianionic selenium. BiCuOSe exhibits a relatively high
      electrical conductivity (sigma approximately 3.3 S cm(-1)) and a reduced band gap
      (E(g) = 0.75 eV), which compare favorably with the optoelectronic properties of
      BiCuOS and the cerium-based oxysulfides, CeAgOS and CeCuOS.

PMID- 18831581
TI  - Racemic atropisomeric N,N-chelate ligands for recognizing chiral carboxylates via
      Zn(II) coordination: structure, fluorescence, and circular dichroism.
AB  - Two racemic atropisomeric N,N'-chelate ligands, bis{3,3'-[N-Ph-2-(2'-py)indolyl]}
      (1) and bis{3,3'-N-4-[N-2-(2'-py)indolyl]phenyl-2-(2'-py)indolyl} (2), have been
      found to be able to distinguish the enantiomers of Zn((R)-BrMeBu)2 and Zn((S)
      BrMeBu)2 where BrMeBu = O2CCH(Br)CHMe2, with a distinct and intense CD spectral
      response at approximately the 10 microM concentration range. Computational
      studies established that the (R)-1-Zn((R)-BrMeBu)2 or (S)-1-Zn((S)-BrMeBu)2
      diastereomer is more stable than (R)-1-Zn((S)-BrMeBu)2 or (S)-1-Zn((R)-BrMeBu)2.
      In addition, computational studies showed that the CD spectra of (S)-1-Zn((S)
      BrMeBu)2 and (S)-1-Zn((R)-BrMeBu)2 are similar. (1)H NMR spectra confirmed that
      these two diastereomers exist in solution in about a 2:1 ratio for both complexes
      of 1 and 2. The distinct CD response of the racemic ligands 1 and 2 toward the
      chiral zinc(II) carboxylate is therefore attributed to the preferential formation
      of one diastereomer. The binding modes of the zinc(II) salt with ligands 1 and 2
      were established by the crystal structures of the model compounds 1-Zn(tfa)2 and
      2-Zn(tfa)2 (tfa = CF3CO2(-)), where the Zn(II) ion is chelated by the two central
      pyridyl groups in the ligand. Fluorescent titration experiments with various
      zinc(II) salts showed that the fluorescent spectrum of the atropisomeric ligand
      displays an anion-dependent change. The zinc(II) binding strength to the N,N'
      chelate site of the atropisomeric ligand has been found to play a key role in the
      selective recognition of different chiral zinc(II) carboxylate derivatives by the
      racemic atropisomeric ligands.

PMID- 18831582
TI  - Ruthenium-catalyzed dehydrogenation of ammonia boranes.
AB  - The dehydrogenation of ammonia borane (AB) and methylammonia borane (MeAB) is
      shown to be catalyzed by several Ru-amido complexes. Up to 1 equiv of H2 (1.0
      system wt %) is released from AB by as little as 0.03 mol % Ru within 5 min, and
      up to 2 equiv of H2 (3.0 system wt %) are released from MeAB with 0.5 mol % Ru in
      under 10 min at room temperature, the first equivalent emerging within 10 s.
      Also, a mixture of AB/MeAB yields up to 3.6 system wt % H2 within 1 h with 0.1
      mol % Ru. Computational studies were performed to elucidate the mechanism of
      dehydrogenation of AB. Finally, it was shown that alkylamine-boranes can serve as
      a source of H2 in the Ru-catalyzed reduction of ketones and imines.

PMID- 18831583
TI  - NMR-based mapping of disulfide bridges in cysteine-rich peptides: application to
      the mu-conotoxin SxIIIA.
AB  - Disulfide-rich peptides represent a megadiverse group of natural products with
      very promising therapeutic potential. To accelerate their functional
      characterization, high-throughput chemical synthesis and folding methods are
      required, including efficient mapping of multiple disulfide bridges. Here, we
      describe a novel approach for such mapping and apply it to a three-disulfide
      bridged conotoxin, mu-SxIIIA (from the venom of Conus striolatus), whose
      discovery is also reported here for the first time. Mu-SxIIIA was chemically
      synthesized with three cysteine residues labeled 100% with (15)N/(13)C, while the
      remaining three cysteine residues were incorporated using a mixture of 70%/30%
      unlabeled/labeled Fmoc-protected residues. After oxidative folding, the major
      product was analyzed by NMR spectroscopy. Sequence-specific resonance assignments
      for the isotope-enriched Cys residues were determined with 2D versions of
      standard triple-resonance ((1)H, (13)C, (15)N) NMR experiments and 2D [(13)C,
      (1)H] HSQC. Disulfide patterns were directly determined with cross-disulfide NOEs
      confirming that the oxidation product had the disulfide connectivities
      characteristic of mu-conotoxins. Mu-SxIIIA was found to be a potent blocker of
      the sodium channel subtype Na(V)1.4 (IC50 = 7 nM). These results suggest that
      differential incorporation of isotope-labeled cysteine residues is an efficient
      strategy to map disulfides and should facilitate the discovery and structure
      function studies of many bioactive peptides.

PMID- 18831584
TI  - Chiral periodic mesoporous organosilicates based on axially chiral monomers:
      transmission of chirality in the solid state.
AB  - Chiral mesoporous materials have been prepared with purely organic monomers
      employing an enantiomerically pure biphenyl bis-siloxane as a dopant along with
      simple 4,4'-bis(triethoxysilyl)biphenyl as the bulk material. Analysis of these
      materials by CD spectroscopy indicates the formation of new chiral aggregates in
      the solid state consistent with charge delocalization from adjacent aryl rings in
      close contact. These aggregates are only observed when the biphenyl and
      enantiomerically pure biaryl are both present. The red-shift resulting of the CD
      signal resulting from these interactions is modeled computationally using time
      dependent DFT calculations.

PMID- 18831585
TI  - Acetylacetonate anchors for robust functionalization of TiO2 nanoparticles with
      Mn(II)-terpyridine complexes.
AB  - A novel class of derivatized acetylacetonate (acac) linkers for robust
      functionalization of TiO2 nanoparticles (NPs) under aqueous and oxidative
      conditions is reported. The resulting surface adsorbate anchors are particularly
      relevant to engineering photocatalytic and photovoltaic devices since they can be
      applied to attach a broad range of photosensitizers and photocatalytic complexes
      and are not affected by humidity. Acac is easily modified by CuI-mediated
      coupling reactions to provide a variety of scaffolds, including substituted terpy
      complexes (terpy = 2,2':6,2''-terpyridine), assembled with ligands coordinated to
      transition-metal ions. Since Mn-terpy complexes are known to be effective
      catalysts for oxidation chemistry, functionalization with Mn(II) is examined.
      This permits visible-light sensitization of TiO2 nanoparticles due to interfacial
      electron transfer, as evidenced by UV-vis spectroscopy of colloidal thin films
      and aqueous suspensions. The underlying ultrafast interfacial electron injection
      is complete on a subpicosecond time scale, as monitored by optical pump-terahertz
      probe transient measurements and computer simulations. Time-resolved measurements
      of the Mn(II) EPR signal at 6 K show that interfacial electron injection induces
      Mn(II) --> Mn(III) photooxidation, with a half-time for regeneration of the
      Mn(II) complex of ca. 23 s.

PMID- 18831586
TI  - A metal-organic nanotube exhibiting reversible adsorption of (H2O)12 cluster.
AB  - A novel 1D metal-organic nanotube, exhibiting reversible and fast adsorption of
      the (H2O)12 cluster, has been synthesized and characterized.

PMID- 18831587
TI  - Selective detection of protein crystals by second harmonic microscopy.
AB  - The unique symmetry properties of second harmonic generation (SHG) microscopy
      enabled sensitive and selective imaging of protein microcrystals with negligible
      contributions from solvated proteins or amorphous protein aggregates. In studies
      of microcrystallites of green fluorescent protein (GFP) prepared in 500 pL
      droplets, the SHG intensities rivaled those of fluorescence, but with superb
      selectivity for crystalline regions. GFP in amorphous aggregates and in solution
      produced substantial background fluorescence, but no detectable SHG. The ratio of
      the forward-to-backward detected SHG provides a measure of the particle size,
      suggesting detection limits down to crystallites 100 nm in diameter under low
      magnification (10x). In addition to being sensitive and highly selective, second
      order nonlinear optical imaging of chiral crystals (SONICC) is directly
      compatibility with virtually all common protein crystallization platforms.

PMID- 18831588
TI  - Catalytic intermolecular allylic C-H alkylation.
AB  - The first electrophilic Pd(II)-catalyzed allylic C H alkylation is reported,
      providing a novel method for formation of sp3-sp3 C C bonds directly from C H
      bonds. A wide range of aromatic and heteroaromatic linear (E)-alpha-nitro
      arylpentenoates are obtained as single olefin isomers in excellent yields
      directly from terminal olefin substrates and methyl nitroacetate. The use of DMSO
      as a pi-acidic ligand was found to be crucial for promoting functionalization of
      the pi-allylPd intermediate. Products from this reaction are valuable synthetic
      intermediates and are readily transformed to amino esters via selective reduction
      and optically enriched alpha,alpha-disubstituted amino acid precursors via
      asymmetric conjugate addition.

PMID- 18831590
TI  - Polycyclic aromatic hydrocarbons in spanish olive oils: relationship between
      benzo(a)pyrene and total polycyclic aromatic hydrocarbon content.
AB  - Samples of Spanish virgin olive oils (VOOs) from different categories, origins,
      varieties, and commercial brands were analyzed by HPLC with a programmable
      fluorescence detector to determine the content of nine heavy polycyclic aromatic
      hydrocarbons (PAHs): benzo(a)anthracene, chrysene, benzo(e)pyrene,
      benzo(b)fluoranthene, benzo(k)fluoranthene, benzo(a)pyrene,
      dibenzo(a,h)anthracene, benzo(g,h,i)perilene, and indeno(1,2,3-c,d)pyrene.
      Samples of olive pomace and crude olive pomace oils were also investigated.
      Benzo(a)pyrene concentrations were below the allowed limit in the European Union
      (2 microg/kg) in 97% of the VOO samples. Only those samples coming from
      contaminated olive fruits or obtained in oil mills with highly polluted
      environments exceeded this value. High correlation coefficients (<0.99) were
      obtained between the contents of benzo(a)pyrene and the sum of the nine PAHs for
      all of the analyzed categories, suggesting that benzo(a)pyrene could be used as a
      marker of the content of these nine PAHs in olive oils.

PMID- 18831589
TI  - Vinylogous ureas as a novel class of inhibitors of reverse transcriptase
      associated ribonuclease H activity.
AB  - High-throughput screening of National Cancer Institute libraries of synthetic and
      natural compounds identified the vinylogous ureas 2-amino-5,6,7,8-tetrahydro-4 H
      cyclohepta[ b]thiophene-3-carboxamide (NSC727447) and N-[3-(aminocarbonyl)-4,5
      dimethyl-2-thienyl]-2-furancarboxamide (NSC727448) as inhibitors of the
      ribonuclease H (RNase H) activity of HIV-1 and HIV-2 reverse transcriptase (RT).
      A Yonetani-Theorell analysis demonstrated that NSC727447, and the active-site
      hydroxytropolone RNase H inhibitor beta-thujaplicinol were mutually exclusive in
      their interaction with the RNase H domain. Mass spectrometric protein
      footprinting of the NSC727447 binding site indicated that residues Cys280 and
      Lys281 in helix I of the thumb subdomain of p51 were affected by ligand binding.
      Although DNA polymerase and pyrophosphorolysis activities of HIV-1 RT were less
      sensitive to inhibition by NSC727447, protein footprinting indicated that
      NSC727447 occupied the equivalent region of the p66 thumb. Site-directed
      mutagenesis using reconstituted p66/p51 heterodimers substituted with natural or
      non-natural amino acids indicates that altering the p66 RNase H primer grip
      significantly affects inhibitor sensitivity. NSC727447 thus represents a novel
      class of RNase H antagonists with a mechanism of action differing from active
      site, divalent metal-chelating inhibitors that have been reported.

PMID- 18831591
TI  - Novel process of fermenting black soybean [Glycine max (L.) Merrill] yogurt with
      dramatically reduced flatulence-causing oligosaccharides but enriched soy
      phytoalexins.
AB  - Black soybeans [Glycine max (L.) Merrill] were germinated under fungal stress
      with food grade R. oligosporus for 3 days and were homogenized and fermented with
      lactic acid bacteria (LAB) to produce soy yogurt. Fungal stress led to the
      generation of oxylipins [oxooctadecadienoic acids (KODES) isomers and their
      respective glyceryl esters] and glyceollins--a type of phytoalexins unique to
      soybeans. In soy yogurt, the concentrations of total KODES and total glyceollins
      were 0.678 mg/g (dry matter) and 0.953 mg/g, respectively. The concentrations of
      other isoflavones (mainly genistein and daidzein and their derivatives) in soy
      yogurt remained largely unchanged after the processes compared with the control
      soy yogurt. Germination of black soybean under fungal stress for 3 days was
      sufficient to reduce stachyose and raffinose (which cause flatulence) by 92 and
      80%, respectively. With a pH value of 4.42, a lactic acid content of 0.262%, and
      a maximum viable cell count of 2.1 x 10 (8) CFU/mL in the final soy yogurt, soy
      milk from germinated soybeans under fungal stress was concluded to be a suitable
      medium for yogurt-making. The resulting soy yogurt had significantly altered
      micronutrient profiles with significantly reduced oligosaccharides and enriched
      glyceollins.

PMID- 18831592
TI  - Biofunctionalization of biomaterials for accelerated in situ endothelialization:
      a review.
AB  - The higher patency rates of cardiovascular implants, including vascular bypass
      grafts, stents, and heart valves are related to their ability to inhibit
      thrombosis, intimal hyperplasia, and calcification. In native tissue, the
      endothelium plays a major role in inhibiting these processes. Various
      bioengineering research strategies thereby aspire to induce endothelialization of
      graft surfaces either prior to implantation or by accelerating in situ graft
      endothelialization. This article reviews potential bioresponsive molecular
      components that can be incorporated into (and/or released from) biomaterial
      surfaces to obtain accelerated in situ endothelialization of vascular grafts.
      These molecules could promote in situ endothelialization by the mobilization of
      endothelial progenitor cells (EPC) from the bone marrow, encouraging cell
      specific adhesion (endothelial cells (EC) and/or EPC) to the graft and, once
      attached, by controlling the proliferation and differentiation of these cells. EC
      and EPC interactions with the extracellular matrix continue to be a principal
      source of inspiration for material biofunctionalization, and therefore, the
      latest developments in understanding these interactions will be discussed.

PMID- 18831594
TI  - Unknown Title.

PMID- 18831593
TI  - Enantioselective organocatalytic approach to alpha-methylene-delta-lactones and
      delta-lactams.
AB  - We present the first enantioselective organocatalytic approach for the synthesis
      of alpha-methylene-delta-lactones and delta-lactams. Our methodology utilizes the
      Michael addition of unmodified aldehydes to ethyl 2-(diethoxyphosphoryl)acrylate
      as the key step affording highly enantiomerically enriched adducts, which can be
      transformed into the target compounds maintaining the high stereoselectivity
      achieved in the first step. This methodology has been shown to be general and
      various optically active gamma-substituted alpha-methylene-delta-lactones and
      delta-lactams can be easily accessed.

PMID- 18831595
TI  - Centrifugal propagation of motion adaptation effects across visual space.
AB  - Perceptual distortions induced by adaptation (aftereffects) arise through
      selective changes in the response properties of discrete subpopulations of
      neurons tuned to particular image features at the adapted spatial location. The
      systematic and well-documented increase of cortical receptive field sizes with
      eccentricity dictates that visual aftereffects ought to become less tightly tuned
      for location as stimuli are moved away from fixation. Here, we demonstrate that
      while this pattern holds for archetypal orientation and spatial frequency
      aftereffects, the effects of motion adaptation are characterized by precisely the
      opposite relationship. Surprisingly, adaptation to translational motion close to
      fixation induces distortions of perceived position and dynamic motion
      aftereffects that propagate centrifugally across visual space, resulting in a
      lack of location specificity. In contrast, motion adaptation in more peripheral
      locations produces aftereffects that are largely limited to the adapted spatial
      region. These findings suggest that central motion adaptation has the unique
      capacity to influence the response state of spatially distant neural populations
      that do not themselves encode the adapting stimulus.

PMID- 18831596
TI  - Probing visual consciousness: rivalry between eyes and images.
AB  - During binocular rivalry, one stimulus is visible (dominant), while the other
      stimulus is invisible (suppressed); after a few seconds, perception reverses. To
      determine whether these alternations involve competition between the eyes or
      between the images, we measured suppression depth to monocular probes. We did so
      in conventional rival stimuli and in rival stimuli swapping between the eyes at
      1.5 Hz (both sorts of rivalry were shown either with or without 18-Hz flicker).
      The conventional conditions cause rivalry that could involve either competition
      between the eyes or between the images or both. The eye-swapping conditions cause
      rivalry that could involve competition between the images. Probes were either a
      small spot or a contrast increment to one of the rival stimuli. Using both yes-no
      and forced-choice procedures, we found that conventional conditions yielded large
      suppression depth and that eye-swapping conditions yielded small suppression
      depth. Weak suppression during image rivalry is consistent with conventional
      rivalry's involving competition between eyes and between images and flicker-and
      swap rivalry's involving little, if any competition between eyes and mainly
      competition between images.

PMID- 18831597
TI  - Coming to terms with lightness and brightness: effects of stimulus configuration
      and instructions on brightness and lightness judgments.
AB  - To recover surface reflectance and illuminance from the raw luminance signal, the
      visual system must use prior assumptions and strategies that make use of
      additional sources of information. Indeed, it has been found that depending on
      experimental conditions, lightness (apparent reflectance) may refer to judgments
      that are similar to brightness judgments (apparent luminance), that are similar
      to local brightness-contrast judgments, or that represent an independent third
      dimension of achromatic experience which exists only when the illumination across
      regions of the display is visibly non-uniform (L. E. Arend & B. Spehar, 1993a,
      1993b). This means that lightness data generated in one experimental condition
      may not be comparable to lightness data measured in other conditions. We
      investigate this problem with regard to a history of data on simultaneous
      brightness-contrast by measuring brightness, brightness-contrast, and lightness
      in stimuli similar to those used in Gilchrist's edge-substitution studies (A.
      Gilchrist, S. Delman, & A. Jacobsen, 1983) and in stimuli similar to those used
      to test Gilchrist's intrinsic-image model against his newer anchoring model (A.
      Gilchrist, 2006). Our results clarify confusions that appear to stem from
      comparing different types of lightness judgments and from inadvertently using
      brightness as an index of lightness under conditions where independent lightness
      judgments are possible.

PMID- 18831598
TI  - The temporal decay of eye gaze adaptation effects.
AB  - Recent findings demonstrate that the perception of other people's eye gaze
      direction can be dramatically biased by previous adaptation to that gaze
      direction. Here, we further investigated this aftereffect by examining its
      development over time, with particular attention to the potential role of the
      ambiguity of the test stimulus. Following adaptation to gaze to one direction,
      participants' ability to correctly classify gaze to the adapted direction was
      severely impaired, both for ambiguous and relatively unambiguous test stimuli. Of
      particular importance, this aftereffect decreased over time but remained
      measurable up to 7 minutes post adaptation, with its decline following an
      exponential decay function. The implications of the present findings are
      discussed with respect to both coding mechanisms involved in gaze perception and
      a potential role of adaptation effects in real life situations.

PMID- 18831599
TI  - Toward a model of microsaccade generation: the case of microsaccadic inhibition.
AB  - Microsaccades are one component of the small eye movements that constitute
      fixation. Their implementation in the oculomotor system is unknown. To better
      understand the physiological and mechanistic processes underlying microsaccade
      generation, we studied microsaccadic inhibition, a transient drop of microsaccade
      rate, in response to irrelevant visual and auditory stimuli. Quantitative
      descriptions of the time course and strength of inhibition revealed a strong
      dependence of microsaccadic inhibition on stimulus characteristics. In Experiment
      1, microsaccadic inhibition occurred sooner after auditory than after visual
      stimuli and after luminance-contrast than after color-contrast visual stimuli.
      Moreover, microsaccade amplitude strongly decreased during microsaccadic
      inhibition. In Experiment 2, the latency of microsaccadic inhibition increased
      with decreasing luminance contrast. We develop a conceptual model of microsaccade
      generation in which microsaccades result from fixation-related activity in a
      motor map coding for both fixation and saccades. In this map, fixation is
      represented at the central site. Saccades are generated by activity in the
      periphery, their amplitude increasing with eccentricity. The activity at the
      central, fixation-related site of the map predicts the rate of microsaccades as
      well as their amplitude and direction distributions. This model represents a
      framework for understanding the dynamics of microsaccade behavior in a broad
      range of tasks.

PMID- 18831600
TI  - Differential changes in human perception of speed due to motion adaptation.
AB  - Visual systems adapt to the prevailing image conditions. This improves the
      ability to discriminate between two similar stimuli but has the side effect that
      veridical perception is degraded. For example, prolonged driving at 100 km/h may
      reduce the perceived speed to 80 km/h but improve the sensitivity to changes in
      the prevailing speed. Here we use radially expanding flow fields with a wide
      combination of adapt and test speeds to study human speed perception. Adaptation
      at speeds higher than the test always attenuates perceived speed, whereas
      adaptation at low and testing at high speeds increases perceived speed. We show
      that adaptation is stronger (i.e., post-adaptation speeds are perceived as
      slower) when the dots in the expanding flow field accelerate towards the
      periphery rather than traveling at constant speeds. We also show that speed
      discriminability is reduced following adaptation to low speeds when tested at
      high speeds and increased when the test speed is at or below prior adaptation
      speeds. We conclude that the relative speeds of the adaptation and test patterns
      are important parameters governing speed-related adaptation effects in the human
      brain.

PMID- 18831601
TI  - Adaptation to invisible motion results in low-level but not high-level
      aftereffects.
AB  - After prolonged exposure to moving stimuli, illusory motion is perceived in
      stimuli that do not contain consistent motion, a phenomenon termed the motion
      aftereffect (MAE). In this study, we tested MAEs under binocular suppression that
      renders the motion adaptor invisible for the entire adaptation period. We
      developed a variant of the continuous flash suppression method to reliably
      suppress target motion stimuli for durations longer than several tens of seconds.
      Here, we ask whether motion systems are functional in the absence of perception
      by measuring the MAE, a question difficult to address using binocular rivalry
      that accompanies a switch of percept between visible and invisible. Results show
      that both the MAEs with static and dynamic tests are attenuated with an invisible
      adaptor when the adaptor and the test stimulus are presented to the same eye. In
      contrast, when the test pattern was presented to the other eye, the dynamic MAE
      was observed in invisible adaptor conditions. These results indicate that low
      level adaptation survives under total binocular suppression, a finding predicted
      by previous studies. In contrast, disappearance of interocular transfer in the
      dynamic MAE suggests that a high-level motion detector does not operate when the
      motion adaptor is rendered invisible.

PMID- 18831602
TI  - Photoreceptor processing improves salience facilitating small target detection in
      cluttered scenes.
AB  - Target detection amidst clutter is a challenging task for both natural and
      artificial vision, yet one solved at the level of neurons in the 3rd optic
      ganglion of insects. These neurons are capable of responding to the motion of
      small objects, even against complex moving backgrounds. While the basic
      physiology has been investigated, little is known about how these cells are able
      to reject background motion while robustly responding to such small stimuli. By
      recording intracellularly from fly photoreceptors stimulated with natural image
      sequences containing a target viewed against a complex moving background, we show
      that the process of target detection begins at the earliest stages of vision. The
      temporal processing by photoreceptors alone, in the absence of any spatial
      interactions, improved the discrimination of targets (essentially a spatial task)
      by around 70%. This enhancement of target salience can be explained by elaborate
      models of photoreceptor temporal non-linear dynamics. The application of the
      functional principals outlined in this work could be utilized in areas such as
      robotics and surveillance, medical imaging, or astronomy, anywhere it is
      necessary to detect a small item from a cluttered surround.

PMID- 18831603
TI  - A 'dipper' function for texture discrimination based on orientation variance.
AB  - We measured the just-noticeable difference (JND) in orientation variance between
      two textures (Figure 1) as we varied the baseline (pedestal) variance present in
      both textures. JND's first fell as pedestal variance increased and then rose,
      producing a 'dipper' function similar to those previously reported for contrast,
      blur, and orientation-contrast discriminations. A dipper function (both
      facilitation and masking) is predicted on purely statistical grounds by a noisy
      variance-discrimination mechanism. However, for two out of three observers, the
      dipper function was significantly better fit when the mechanism was made
      incapable of discriminating between small sample variances. We speculate that a
      threshold nonlinearity like this prevents the visual system from including its
      intrinsic noise in texture representations and suggest that similar thresholds
      prevent the visibility of other artifacts that sensory coding would otherwise
      introduce, such as blur.

PMID- 18831604
TI  - Driving around bends with manipulated eye-steering coordination.
AB  - This study investigated the link between drivers' gaze positioning and steering
      behavior when negotiating bends. This was conducted by directing the driver's
      point of gaze toward a target situated in the vicinity of the tangent point (TP),
      a region known to attract a significant amount of ocular fixations and thought to
      provide some useful input for anticipatory steering (M. F. Land & D. N. Lee,
      1994). The orientation of gaze relative to the TP was manipulated and the
      resulting steering behavior was compared to that obtained with a free-gaze
      strategy. The data revealed that constraining eye movements did not impair
      steering behavior. On the contrary, the continuous tracking of the fixation point
      promoted smoother steering control, irrespective of the position of that point.
      This confirms that previewing the road curvature by tracking a distant point
      contributes to the stability of steering. The direction of the TP does not appear
      to be an essential parameter in that process (D. D. Salvucci & R. Gray, 2004).
      The results also indicate that continuously looking at the TP or further inside
      the bend yielded a deviation of the trajectory. This is consistent with the
      hypothesis that drivers look inside the lane boundaries to determine the future
      path (R. M. Wilkie & J. P. Wann, 2006).

PMID- 18831605
TI  - Three-dimensional object shape from shading and contour disparities.
AB  - Both non-Lambertian shading, specularities in particular, and occluding contours
      have ill-matched binocular disparities. For example, the disparities of
      specularities depend not only on a surface's position but also on its curvature.
      Shading and contour disparities do in general not specify a point on the surface.
      I investigated how shading and contours contribute to perceived shape in
      stereoscopic viewing. Observers adjusted surface attitude probes on a globular
      object. In Experiment 1, the object was either Lambertian or Lambertian with
      added specularities. In the next experiment, I removed the Lambertian part of the
      shading. In Experiment 3, I reduced the disparity of the contour to zero, and in
      Experiment 4, I removed both cues. There was little effect of shading condition
      in Experiment 1. Removing the Lambertian shading in Experiment 2 rendered the
      sign of the surface ambiguous (convex/concave) although all surfaces were
      perceived as curved. Results in Experiment 3 were similar to those in Experiment
      1. Removing both cues in Experiment 4 made all surfaces appear flat for three
      observers and convex for one observer. I conclude that in the absence of
      Lambertian shading, observers have categorically different perceptions of the
      surface depending on whether disparate specular highlights and disparate contours
      are present or not.

PMID- 18831606
TI  - Learning novel mappings from optic flow to the control of action.
AB  - Many perceptual-motor skills can be captured in terms of mappings from
      information in sensory arrays to movements of the body, but little is known about
      how these mappings are acquired and updated. The present study demonstrates that
      people adapt to changes in the dynamics of a controlled system by learning novel
      mappings from information in optic flow to movement of the system. Two groups of
      subjects performed a simulated braking task, using a foot pedal to decelerate to
      a stop at a target. Brake dynamics were manipulated such that deceleration was
      proportional to pedal position for one group, and both pedal position and current
      speed for the other group. Both groups adapted to their respective brake dynamics
      by learning to use different combinations of optic flow field variables,
      revealing a form of adaptation that has not been previously reported, but likely
      plays a critical role in robust visuomotor control.

PMID- 18831607
TI  - The twinkle aftereffect is pre-cortical and is independent of filling-in.
AB  - A real or artificial scotoma within a dynamic noise field fills in within a few
      seconds. When the dynamic noise is replaced with a homogenous field, a twinkling
      after effect (TwAE) is induced exclusively in the location of the former scotoma.
      We are employing the appearance of the TwAE to perform rapid perimetry in
      patients with retinal scotomas. To analyze the loci within the visual system and
      the mechanisms of filling-in and the TwAE, we examined their orientation tuning,
      inter-ocular transfer, and threshold versus contrast functions by measuring
      contrast detection thresholds for stimuli presented in areas that were filled-in
      or contained the TwAE. For filling-in, detection thresholds were narrowly tuned
      for orientation, transferred interocularly, and rose monotonically with the
      contrast of a surround pattern. These results indicate that surround suppression
      and filling-in involve inhibitory processes originating at cortical stages of
      visual processing. Threshold versus contrast functions were weakly dipper-shaped
      for the TwAE, did not transfer inter-ocularly, and were not tuned for
      orientation. These results indicate that the TwAE involves additive noise that is
      pre-cortical in origin and that it is distinct from filling-in.

PMID- 18831608
TI  - Perceiving illusory contours: figure detection and shape discrimination.
AB  - We investigate the relationship between illusory figure detection and
      discrimination of its shape, asking whether these depend on a single, two
      separate, or two sequential processes. In a simultaneous detection-discrimination
      experiment, we presented subjects with brief, backward-masked Kanizsa-type
      patterns consisting of four "pacmen," arranged as if at the corners of a 60
      degree parallelogram. Pacman openings were oriented in a quarter of the trials so
      as to induce an illusory parallelogram. In another quarter, three of the pacmen
      induced an equilateral triangle. In the remaining half, pacmen were rotated so as
      not to induce a complete figure. For each trial, subjects reported whether they
      perceived an illusory figure (detection) and which shape they saw
      (discrimination), "guessing" the shape even when it was not explicitly perceived.
      Average detection and discrimination psychometric curves were similar with
      significantly better-than-chance detection and discrimination beginning at
      approximately 100 ms. Nevertheless, we found three patterns of performance,
      representing different detection-discrimination relationships, suggesting these
      may be separate processes. Detection was not always followed by correct
      discrimination, especially for poorer performers. Interestingly there were also
      cases where discrimination was accurate, even without detection, especially in
      mid-level performers. One detection-discrimination interaction was that only with
      explicit detection did shape discrimination use local features (such as the
      orientation of the fourth pacman in the case of an illusory triangle). We suggest
      that illusory figure detection and shape discrimination are separate tasks, with
      their relationship being determined individually.

PMID- 18831609
TI  - Development of visually driven postural reactivity: a fully immersive virtual
      reality study.
AB  - The objective of this study was to investigate the development of visually driven
      postural regulation in typically developing children of different ages. Thirty
      two typically developing participants from 5 age groups (5-7 years, 8-11 years,
      12-15 years, 16-19 years, or 20-25 years) were asked to stand within a virtual
      tunnel that oscillated in an anterior-posterior fashion at three different
      frequencies (0.125, 0.25, and 0.5 Hz). Body sway (BS) and postural perturbations
      (as measured by velocity root mean squared or vRMS) were measured. Most of the 5-
      to 7-year-old participants (67%) were unable to remain standing during the
      dynamic conditions. For older participants, BS decreased significantly with age
      for all frequencies. Moreover, vRMS decreased significantly from the 8- to 11-
      through 16- to 19-years age groups (greatest decreases for 0.5 Hz, followed by
      0.25-Hz and 0.125-Hz conditions). No difference of frequency or instability was
      found between the 16- to 19- and 20- to 25-year-old groups for most conditions.
      Results suggest an over-reliance on visual input relative to proprioceptive and
      vestibular inputs on postural regulation at young ages (5-7 years). The finding
      that vRMS decreased significantly with age before stabilizing between 16 and 19
      years suggests an important transitory period for sensorimotor development within
      this age range.

PMID- 18831610
TI  - Integrated global motion influences smooth pursuit in infants.
AB  - Smooth pursuit eye movements (SP) were studied in 5- and 9-month-old infants and
      adults in response to a rhombus oscillating horizontally behind three spatially
      separated vertical occluders. During motion, the rhombus vertices were never
      visible. Thus the perception of the global motion of the rhombus required
      integration of its moving visible segments. We tested whether infants were able
      to use such perceived global motion for SP in two different occluder conditions;
      one in which the occluder was clearly visible to the observer and one in which it
      was invisible. In adults, the presence of a visible occluder hiding the vertices
      of the rhombus strongly facilitates the perception of the global motion. It was
      found that adults and 9-month-olds performed significantly more horizontal SP in
      the presence of a visible occluder but not 5-month-olds. Furthermore, this
      tendency was strengthened over single trials, and this temporal pattern was very
      similar in all age groups. In the invisible occluder condition both adults and
      infants tracked the segments of the rhombus primarily with vertical SP. It was
      concluded that the ability to integrate moving object fragments into perceived
      global motion and use that to regulate SP develops into adult performance by 9
      months of age.

PMID- 18831611
TI  - Multiple mechanisms of illusory contour perception.
AB  - A variety of mechanisms have been proposed to explain illusory contour formation.
      However, since prior studies have focused on a single mechanism, there is no
      clear consensus regarding contour formation mechanisms. Here we developed a novel
      vivid dynamic display we call the chomping pacman that allows measurement of
      minute differences in contour clarity. This illusion is shown to be more vivid
      than traditional static displays. Using the method of adjustment, we are able to
      identify three mechanisms of contour formation: extrapolation, interpolation, and
      figural. We posit that these three mechanisms combine to form the general
      illusory contour percept in traditional static Kanizsa displays and likely
      contribute to real-world contour perception.

PMID- 18831612
TI  - Voluntary control of long-range motion integration via selective attention to
      context.
AB  - Ambiguous stimuli can look different in different contexts. Here we demonstrate
      that subjective appearance of motion depends not only on current visual input but
      critically on which aspects of the context are attended. Observers fixated a
      central oblique test grating flanked by two pairs of orthogonally oriented
      context gratings arranged in a cross (+) configuration. Each context pair could
      induce the test stimulus to appear to switch from diagonal motion to either
      horizontal motion (due to one context pair) or vertical motion (due to the
      other). Spontaneous switching between these motion states was observed under free
      viewing. We demonstrate that observers can voluntarily select between specific
      states when cued to attend selectively to one or other context pair in an
      alternating manner. Concurrent reports of perceived test stimulus motion depended
      specifically on which context was currently attended, indicating a high degree of
      "cued-control" over subjective state via attended context. Further experiments
      established that the perception was nevertheless still constrained by physical
      stimulus context as well as by attentional selection among that context.
      Moreover, the attentional control evident here did not seem reducible solely to
      local contrast gain modulation of the attended vs. ignored context elements.
      Selective attention to different parts of the context can evidently resolve the
      ambiguity of the test grating, with integration arising selectively for those
      components that are jointly attended. Such selective integration can result in
      substantial voluntarily controlled changes in phenomenal perception.

PMID- 18831613
TI  - Disparity statistics in natural scenes.
AB  - Binocular disparity is the input to stereopsis, which is a very strong depth cue
      in humans. However, the distribution of binocular disparities in natural
      environments has not been quantitatively measured. In this study, we converted
      distances from accurate range maps of forest scenes and indoor scenes into the
      disparities that an observer would encounter, given an eye model and fixation
      distances (which we measured for the forest environment, and simulated for the
      indoor environment). We found that the distributions of natural disparities in
      these two kinds of scenes are centered at zero, have high peaks, and span about 5
      deg, which closely matches the macaque MT cells' disparity tuning range. These
      ranges are fully within the operational range of human stereopsis determined
      psychophysically. Suprathreshold disparities (>10 arcsec) are common rather than
      exceptional. There is a prevailing notion that stereopsis only operates within a
      few meters, but our finding suggests that we should rethink the role of
      stereopsis at far viewing distances because of the abundance of suprathreshold
      disparities.

PMID- 18831614
TI  - Distortion in perceived image size accompanies flash lag in depth.
AB  - The flash-lag effect -- a misperception that a flashed object appears to lag
      behind a moving object despite their physical alignment -- has mainly been
      investigated as a spatiotemporal offset. Here, we report that the flash-lag-in
      depth effect is accompanied by an illusory change in the apparent size of the
      flashed object. We found a strong flash-lag-in-depth effect with a dot-defined
      square, whose motion in depth was signaled by changing retinal disparity
      (stereomotion), and a Gaussian blob that was flashed in the center of the square.
      Using the same stimulus, observers matched the apparent size of the flashed blob
      with a reference blob when the square moved with approaching or receding motion.
      Approaching motion of the square resulted in a reduction in the apparent size of
      the flashed blob, and an apparent enlargement of the flashed blob was induced by
      receding motion of the square. Additionally, this size effect substantially
      diminished, or was eliminated, when looming (change of size) instead of
      stereomotion was used to cue motion in depth of the square. The flashed-object
      size change that is induced by the moving square is not explained by simple
      predictions from projective geometry.

PMID- 18831615
TI  - Mobile computation: spatiotemporal integration of the properties of objects in
      motion.
AB  - We demonstrate that, as an object moves, color and motion signals from
      successive, widely spaced locations are integrated, but letter and digit shapes
      are not. The features that integrate as an object moves match those that
      integrate when the eyes move but the object is stationary (spatiotopic
      integration). We suggest that this integration is mediated by large receptive
      fields gated by attention and that it occurs for surface features (motion and
      color) that can be summed without precise alignment but not shape features
      (letters or digits) that require such alignment. Rapidly alternating pairs of
      colors and motions were presented at several locations around a circle centered
      at fixation. The same two stimuli alternated at each location with the phase of
      the alternation reversing from one location to the next. When observers attended
      to only one location, the stimuli alternated in both retinal coordinates and in
      the attended stream: feature identification was poor. When the observer's
      attention shifted around the circle in synchrony with the alternation, the
      stimuli still alternated at each location in retinal coordinates, but now
      attention always selected the same color and motion, with the stimulus appearing
      as a single unchanging object stepping across the locations. The maximum
      presentation rate at which the color and motion could be reported was twice that
      for stationary attention, suggesting (as control experiments confirmed) object
      based integration of these features. In contrast, the identification of a letter
      or digit alternating with a mask showed no advantage for moving attention despite
      the fact that moving attention accessed (within the limits of precision for
      attentional selection) only the target and never the mask. The masking apparently
      leaves partial information that cannot be integrated across locations, and we
      speculate that for spatially defined patterns like letters, integration across
      large shifts in location may be limited by problems in aligning successive
      samples. Our results also suggest that as attention moves, the selection of any
      given location (dwell time) can be as short as 50 ms, far shorter than the
      typical dwell time for stationary attention. Moving attention can therefore
      sample a brief instant of a rapidly changing stream if it passes quickly through,
      giving access to events that are otherwise not seen.

PMID- 18831616
TI  - Time course and robustness of ERP object and face differences.
AB  - Conflicting results have been reported about the earliest "true" ERP differences
      related to face processing, with the bulk of the literature focusing on the
      signal in the first 200 ms after stimulus onset. Part of the discrepancy might be
      explained by uncontrolled low-level differences between images used to assess the
      timing of face processing. In the present experiment, we used a set of faces,
      houses, and noise textures with identical amplitude spectra to equate energy in
      each spatial frequency band. The timing of face processing was evaluated using
      face-house and face-noise contrasts, as well as upright-inverted stimulus
      contrasts. ERP differences were evaluated systematically at all electrodes,
      across subjects, and in each subject individually, using trimmed means and
      bootstrap tests. Different strategies were employed to assess the robustness of
      ERP differential activities in individual subjects and group comparisons. We
      report results showing that the most conspicuous and reliable effects were
      systematically observed in the N170 latency range, starting at about 130-150 ms
      after stimulus onset.

PMID- 18831617
TI  - The McCollough effect reflects permanent and transient adaptation in early visual
      cortex.
AB  - The brain encounters input varying with many different time courses. Given such
      temporal variability, it would seem practical for adaptation to operate at
      multiple timescales. Indeed, to account for peculiar effects such as spacing,
      savings, and spontaneous recovery, many recent models of learning and adaptation
      have postulated multiple mechanisms operating at different timescales. However,
      despite this assumption, and compelling modelling results, different timescales
      of cortical adaptation and learning are rarely isolated in behaving animals. Here
      we demonstrate in a series of experiments that early visual cortex adapts at two
      distinct and separable timescales: fast (saturating with a time constant of
      roughly 30 seconds) and infinite (a perfect integrator: exhibiting no signs of
      decay or diminishing returns within the range of intervals tested). We further
      demonstrate that these two timescales sum linearly and appear to be operating
      independently and in parallel.

PMID- 18831618
TI  - Quantitative assessment of divergence eye movements.
AB  - PURPOSE: This study sought to quantify divergence eye movements and differences
      between divergence and convergence to smoothly moving ramp, step, and
      disappearing step stimuli. METHODS: Eight visually normal, adult subjects
      participated in three experiments investigating the dynamics of responses using
      an infrared limbal eye tracker. RESULTS: There were four primary findings: (1) a
      smooth tracking behavior was observed for slow ramps while the fast ramps
      elicited smooth tracking combined with a high-velocity, step-like behavior; (2)
      the high-velocity components observed in the faster ramps had a similar main
      sequence as divergence steps; (3) divergence dynamics to disappearing steps
      starting at the subject's near dissociated phoria level were similar to
      corresponding step responses; and (4) the high-velocity components from
      divergence ramps were dependent on initial vergence position, whereas the high
      velocity components from convergence ramps were not. CONCLUSION: The results
      suggest a preprogrammed component is present in divergence similar to
      convergence; however, unlike convergence, the high-velocity components from
      divergence ramp responses are dependent on initial vergence position.

PMID- 18831619
TI  - Spatial dependencies between local luminance and contrast in natural images.
AB  - Previous research has suggested only weak statistical dependencies between local
      luminance and contrast in natural images. Here we study luminance and contrast in
      natural images using established measures and show that when multiple
      measurements of these two local quantities are taken in different spatial
      locations across the visual field, strong dependencies are revealed that were not
      apparent in previous pointwise (single-site) analyses. We present a few simple
      experiments demonstrating this spatial dependency of luminance and contrast and
      show that the luminance measurements can be used to approximate the contrast
      measurements. We also show that relying on higher-order statistics, independent
      component analysis learns paired spatial features for luminance and contrast.
      These features are shown to share orientation and localization, with the filters
      corresponding to the features dependent in their outputs. Finally, we demonstrate
      that the found dependencies also exist in artificial images generated from a dead
      leaves model, implying that simple image phenomena may suffice to account for the
      dependencies. Our results indicate that local luminance and contrast computations
      do not recover independent information sources from the visual signal.
      Subsequently, our results predict spatial processing of local luminance and
      contrast to be non-separable in visual systems.

PMID- 18831620
TI  - Induction from a below-threshold chromatic pattern.
AB  - Patterned backgrounds can induce large shifts in color appearance, even with
      patterns of only 10% S-cone contrast (S. K. Shevell & P. Monnier, 2005). The
      present study tested whether a background pattern could induce color shifts even
      at a below-threshold contrast. In the first experiment, S-cone contrast threshold
      for discriminating a pattern from a homogenous background was measured by a 2AFC
      procedure. Next, a test ring was inserted within the patterned background. With
      the test ring present, six of eight observers reliably distinguished trials with
      a patterned background from trials with a homogeneous field, even though the S
      cone contrast in the pattern was too low to be discriminated from a homogeneous
      background. This suggested that a below-threshold S-cone pattern shifted the
      color appearance of the test ring; that is, the appearance of the test was used
      to discriminate whether the background was patterned or homogeneous. This was
      corroborated by asymmetric color matches, which revealed a color shift caused by
      subthreshold S-cone contrast within the patterned background.

PMID- 18831621
TI  - Maximum differentiation (MAD) competition: a methodology for comparing
      computational models of perceptual quantities.
AB  - We propose an efficient methodology for comparing computational models of a
      perceptually discriminable quantity. Rather than comparing model responses to
      subjective responses on a set of pre-selected stimuli, the stimuli are computer
      synthesized so as to optimally distinguish the models. Specifically, given two
      computational models that take a stimulus as an input and predict a perceptually
      discriminable quantity, we first synthesize a pair of stimuli that
      maximize/minimize the response of one model while holding the other fixed. We
      then repeat this procedure, but with the roles of the two models reversed.
      Subjective testing on pairs of such synthesized stimuli provides a strong
      indication of the relative strengths and weaknesses of the two models.
      Specifically, the model whose extremal stimulus pairs are easier for subjects to
      discriminate is the better model. Moreover, careful study of the synthesized
      stimuli may suggest potential ways to improve a model or to combine aspects of
      multiple models. We demonstrate the methodology for two example perceptual
      quantities: contrast and image quality.

PMID- 18831622
TI  - Faces in the cloud: Fourier power spectrum biases ultrarapid face detection.
AB  - Recent results show that humans can respond with a saccadic eye movement toward
      faces much faster and with less error than toward other objects. What feature
      information does your visual cortex need to distinguish between different objects
      so rapidly? In a first step, we replicated the "fast saccadic bias" toward faces.
      We simultaneously presented one vehicle and one face image with different
      contrasts and asked our subjects to saccade as fast as possible to the image with
      higher contrast. This was considerably easier when the target was the face. In a
      second step, we scrambled both images to the same extent. For one subject group,
      we scrambled the orientations of wavelet components (local orientations) while
      preserving their location. This manipulation completely abolished the face bias
      for the fastest saccades. For a second group, we scrambled the phases (i.e., the
      location) of Fourier components while preserving their orientation (i.e., the 2-D
      amplitude spectrum). Even when no face was visible (100% scrambling), the fastest
      saccades were still strongly biased toward the scrambled face image! These
      results suggest that the ability to rapidly saccade to faces in natural scenes
      depends, at least in part, on low-level information contained in the Fourier 2-D
      amplitude spectrum.

PMID- 18831623
TI  - Perceiving an object in its context: is the context cultural or perceptual?
AB  - S. Kitayama, S. Duffy, T. Kawamura, and J. T. Larsen (2003) found that East
      Asians, when shown a line inside a square, memorized more accurately the ratio of
      the line's length relative to the square than the line's absolute length, whereas
      North Americans showed the opposite results. Because of this study's important
      implications on cultural influence to visual perception, we attempted to
      replicate it in China and USA, without success. Our 120 participants as a whole
      estimated a line's relative length more accurately than its absolute length,
      regardless of culture. Our results can be explained by the advantage of an
      explicit frame of reference in the ratio estimation, an advantage well known in
      the literature. Namely, the square as a frame of reference is more useful in the
      relative than in the absolute estimation of the line's length when the size of
      square changed from study to recall.

PMID- 18831624
TI  - The contribution of different facial regions to the recognition of conversational
      expressions.
AB  - The human face is an important and complex communication channel. Humans can,
      however, easily read in a face not only identity information but also facial
      expressions with high accuracy. Here, we present the results of four
      psychophysical experiments in which we systematically manipulated certain facial
      areas in video sequences of nine conversational expressions to investigate
      recognition performance and its dependency on the motions of different facial
      parts. The results help to demonstrate what information is perceptually necessary
      and sufficient to recognize the different facial expressions. Subsequent analyses
      of the facial movements and correlation with recognition performance show that,
      for some expressions, one individual facial region can represent the whole
      expression. In other cases, the interaction of more than one facial area is
      needed to clarify the expression. The full set of results is used to develop a
      systematic description of the roles of different facial parts in the visual
      perception of conversational facial expressions.

PMID- 18831625
TI  - Scan patterns during the processing of facial expression versus identity: an
      exploration of task-driven and stimulus-driven effects.
AB  - Perceptual studies suggest that processing facial identity emphasizes upper-face
      information, whereas processing expressions of anger or happiness emphasizes the
      lower-face. The two goals of the present study were to determine (a) if the
      distributions of eye fixations reflect these upper/lower-face biases, and (b)
      whether this bias is task- or stimulus-driven. We presented a target face
      followed by a probe pair of morphed faces, neither of which was identical to the
      target. Subjects judged which of the pair was more similar to the target face
      while eye movements were recorded. In Experiment 1 the probe pair always differed
      from each other in both identity and expression on each trial. In one block
      subjects judged which probe face was more similar to the target face in identity,
      and in a second block subjects judged which probe face was more similar to the
      target face in expression. In Experiment 2 the two probe faces differed in either
      expression or identity, but not both. Subjects were not informed which dimension
      differed, but simply asked to judge which probe face was more similar to the
      target face. We found that subjects scanned the upper-face more than the lower
      face during the identity task but the lower-face more than the upper-face during
      the expression task in Experiment 1 (task-driven effects), with significantly
      less variation in bias in Experiment 2 (stimulus-driven effects). We conclude
      that fixations correlate with regional variations of diagnostic information in
      different processing tasks, but that these reflect top-down task-driven guidance
      of information acquisition more than stimulus-driven effects.

PMID- 18831626
TI  - How does saccade adaptation affect visual perception?
AB  - Three signals are used to visually localize targets and stimulate saccades: (1)
      retinal location signals for intended saccade amplitude, (2) sensory-motor
      transform (SMT) of retinal signals to extra-ocular muscle innervation, and (3)
      estimates of eye position from extra-retinal signals. We investigated effects of
      adapting saccade amplitude to a double-step change in target location on
      perceived direction. In a flashed-pointing task, subjects pointed an unseen hand
      at a briefly displayed eccentric target without making a saccade. In a sustained
      pointing task, subjects made a horizontal saccade to a double-step target. One
      second after the second step, they pointed an unseen hand at the final target
      position. After saccade-shortening adaptation, there was little change in hand
      pointing azimuth toward the flashed target suggesting that most saccade
      adaptation was caused by changes in the SMT. After saccade-lengthening
      adaptation, there were small changes in hand-pointing azimuth to flashed targets,
      indicating that 1/3 of saccade adaptation was caused by changes in estimated
      retinal location signals and 2/3 by changes in the SMT. The sustained hand
      pointing task indicated that estimates of eye position adapted inversely with
      changes of the SMT. Changes in perceived direction resulting from saccade
      adaptation are mainly influenced by extra-retinal factors with a small retinal
      component in the lengthening condition.

PMID- 18831627
TI  - A multiplicative model for spatial interaction in the human visual cortex.
AB  - Multifocal visual evoked potentials (mfVEP) were recorded simultaneously for both
      the target and the neighbor stimuli, each varying over 6 levels of contrast: 0%,
      4%, 8%, 16%, 32%, and 64%. For most conditions, the relationship between the
      amplitude of target response and the contrast of the neighbor stimulus, as well
      as the amplitude of the response to the target stimulus, were described with a
      simple, normalization model. However, when the neighbor stimulus had a much
      higher contrast than the target stimulus, the amplitude of the target response
      was larger than the prediction from the normalization model. These results
      suggest that spatial interaction observed in the mfVEP requires (1)
      multiplicative mechanisms, (2) mutual inhibition between neighboring regions, and
      (3) a mechanism that saturates when the ratio between the contrasts of the target
      and that of the neighbor is large. A modified multiplicative model that
      incorporates these elements describes the results.

PMID- 18831628
TI  - The intrinsic constraint approach to cue combination: an empirical and
      theoretical evaluation.
AB  - We elucidate two properties of the intrinsic constraint (IC) model of depth cue
      combination (F. Domini, C. Caudek, & H. Tassinari, 2006). First, we show that IC
      combines depth cues in a weighted sum that maximizes the signal-to-noise ratio of
      the combined estimate. Second, we show that IC predicts that any two depth
      matched pairs of stimuli are separated by equal numbers of just noticeable
      differences (JNDs) in depth. That is, IC posits a strong link between perceived
      depth and depth discrimination, much like some Fechnerian theories of sensory
      scaling. We test this prediction, and we find that it does not hold. We also find
      that depth discrimination performance approximately follows Weber's law, whereas
      IC assumes that depth discrimination thresholds are independent of baseline
      stimulus depth.

PMID- 18831629
TI  - Biological motion perception is cue-invariant.
AB  - Previous work investigating whether biological motion is supported by local
      second-order motion has been contradictory, with different groups finding either
      a difference or no difference in performance compared to that obtained with first
      order stimuli. Here we show psychophysically, using randomized-polarity and
      contrast-modulated stimuli, that detection of second-order biological motion
      walkers is worse for stimuli defined by second-order cues, but this difference is
      explained by a difference in visibility of the local motion in the stimuli. By
      mixing first-order and second-order dots within the same stimulus, we show that,
      when the two types of dot are equally visible, first-order noise dots can mask a
      second-order walker, and vice-versa. We also show that direction-discrimination
      of normal, inverted and scrambled walkers follow the same pattern for second
      order as that obtained with first-order stimuli. These results are consistent
      with biological motion being processed by a mechanism that is cue-invariant.

PMID- 18831630
TI  - Spatiotemporal feature attribution for the perception of visual size.
AB  - This study examined the role of spatiotemporal feature attribution in the
      perception of the visual size of objects. A small or a large leading disk, a test
      disk of variable size, and a probe disk of a fixed size were sequentially
      presented at the same position for durations of 16.7 ms with interstimulus
      intervals of 117 ms. Observers compared the visual size of the test with the
      probe disk. The size of the test disk was underestimated and overestimated when
      the test followed small and large leading disks, respectively (Experiment 1).
      These modulations of visual size occurred even when disks were sequentially
      presented so as to invoke apparent motion (Experiment 2). Furthermore, when two
      streams of apparent motion consisting of the three types of disk were diagonally
      overlapped, modulation of visual size occurred in accordance with the size of the
      attended leading disk (Experiment 3). Retinotopic and non-retinotopic feature
      attribution and the related attentional mechanisms are discussed.

PMID- 18831631
TI  - A recurrent model of contour integration in primary visual cortex.
AB  - Physiological and psychophysical studies have demonstrated the importance of
      colinearity in visual processing. Motivated by these empirical findings we
      present a novel computational model of recurrent long-range processing in the
      primary visual cortex. Unlike other models we restrict the long-range interaction
      to cells of parallel orientation with colinear aligned receptive fields. We also
      employ a recurrent interaction using modulatory feedback, in accordance with
      empirical findings. Self-normalizing shunting equations guarantee the saturation
      of activities after a few recurrent cycles. The primary computational goal of the
      model is to evaluate local, often noisy orientation measurements within a more
      global context and to selectively enhance coherent activity by excitatory,
      modulating feedback. All model simulations were done with the same set of
      parameters. We show that the model qualitatively reproduces empirical data of
      response facilitation and suppression for a single bar element depending on the
      local surround outside the classical receptive field (M. K. Kapadia, M. Ito, C.
      D. Gilbert, & G. Westheimer, 1995). Next we evaluate the model performance for
      the processing of artificial and natural images. We quantitatively evaluate the
      model using two measures of contour saliency and orientation significance. We
      show that both measures monotonically increase during the recurrent interaction
      and saturate after a small number of recurrent cycles. The model clarifies how
      basic tasks of early vision can be accomplished within a single, biologically
      plausible architecture.

PMID- 18831632
TI  - Speed perception during acceleration and deceleration.
AB  - We have recently shown that stimulus acceleration affects subsequent preferred
      speed and tuning widths of macaque area MT neurons (A. Schlack, B. Krekelberg, &
      T. D. Albright, 2007). Given the close link between area MT and speed perception,
      this predicts that speed perception should depend on the acceleration context.
      Here, we show that this is indeed the case for both speed discrimination and
      speed perception. Specifically, speed discrimination thresholds improve in an
      acceleration context but absolute speeds are more underestimated than in a
      deceleration context. In line with our physiological data, these changes can be
      understood in terms of speed-dependent adaptation mechanisms in MT and do not
      require an explicit acceleration dependence of speed perception.

PMID- 18831633
TI  - Sensory sluggishness dissociates saccadic, manual, and perceptual responses: an S
      cone study.
AB  - Sensory information travels to visual and motor areas via several distinct
      pathways, some of them being fast-like the achromatic magnocellular and
      retinotectal routes-and others slower-those carrying chromatic signals, in
      particular S-opponent signals. It is debated whether common visual processing
      stages are used for different types of responses, such as initiating saccadic or
      manual responses or making perceptual judgments. The present paper casts new
      light on this question by comparing the participation of fast and slow pathways
      across these responses. In the first experiment, we measured manual and saccadic
      reaction times to luminance and S-cone signals, equated in detectability for each
      participant and presented on either sides of fixation. Our results show that both
      manual and saccadic responses are slower for S-cone stimuli. Most interestingly,
      this reaction time difference was twice as large for saccadic responses as for
      manual responses, suggesting that saccades rely more on the fast signals, not
      supported by S-cone stimuli, than do manual responses. In a second experiment,
      our participants performed temporal order judgments on pairs of luminance and S
      cone stimuli. Our results show no evidence of perceived time discrepancy between
      the two signals, which may imply that perceptual judgments utilize different
      signals from either manual or saccadic responses.

PMID- 18831634
TI  - Topological analysis of population activity in visual cortex.
AB  - Information in the cortex is thought to be represented by the joint activity of
      neurons. Here we describe how fundamental questions about neural representation
      can be cast in terms of the topological structure of population activity. A new
      method, based on the concept of persistent homology, is introduced and applied to
      the study of population activity in primary visual cortex (V1). We found that the
      topological structure of activity patterns when the cortex is spontaneously
      active is similar to those evoked by natural image stimulation and consistent
      with the topology of a two sphere. We discuss how this structure could emerge
      from the functional organization of orientation and spatial frequency maps and
      their mutual relationship. Our findings extend prior results on the relationship
      between spontaneous and evoked activity in V1 and illustrates how computational
      topology can help tackle elementary questions about the representation of
      information in the nervous system.

PMID- 18831635
TI  - Contrast polarity, chromaticity, and stereoscopic depth modulate contextual
      interactions in vernier acuity.
AB  - Vernier alignment thresholds are strongly compromised when the vernier is
      embedded in an array of equal-length flanking lines. Here, we show that these
      contextual interactions can be diminished by giving the flanks the opposite
      contrast polarity, e.g., white flanks surrounding a black vernier. Similar
      results are obtained for red verniers and equiluminant green flanks and when
      vernier and flanks have different binocular disparity. Using special flank
      configurations, we can eliminate location uncertainty as an important factor for
      this kind of contextual interactions. We interpret these results as evidence that
      perceptual grouping of the vernier and the flanks plays an important role in the
      vernier threshold elevation caused by contextual flanks.

PMID- 18831636
TI  - Superposition catastrophe and form-motion binding.
AB  - Numerous studies indicate that perceiving global object motion results from the
      integration of local component motions across space and time. Less attention has
      been paid to the issue of motion selection, necessary to avoid spurious
      associations of component motions belonging to different objects and to solve the
      so-called "superposition catastrophe problem" (F. Rosenblatt, 1961). We address
      this issue using outlines of geometrical shapes moving behind apertures that
      concealed their vertices such that recovering their global motion requires the
      selection and integration of some, but not all, component motions. Depending on
      which local motions are selected for motion integration, these stimuli yield the
      perception of either expansion/contraction, of global translation, or of segments
      moving independently. We show that the selection process depends on local and
      global stimulus parameters, including the local direction of figure's line
      endings or the spatial configuration of component motions. In contrast, motion
      selection depends less on the width-i.e., spatial frequency content-or polarity
      of the edges. Finally, synchronous temporal modulation of component motions in
      the gamma range has little effect on motion selection. These results indicate
      that selecting component motions for motion integration is primarily determined
      by form constraints. As a consequence, current models assuming that mutually
      consistent component motions are bounded in a velocity space-lacking spatial
      organization should be revised to account for the present data. Alternately,
      interactions between visual areas selectively processing form and motion could be
      introduced in order to account for the perceptual binding of moving objects.

PMID- 18831637
TI  - Spatial integration by MT pattern neurons: a closer look at pattern-to-component
      effects and the role of speed tuning.
AB  - The primate visual system faces a difficult problem whenever it encounters the
      motion of an object moving over a patch of the retina. Objects typically contain
      a number of edges at different orientations and so a range of image velocities
      are generated within the receptive field of a neuron processing the object
      movement. It is still a mystery as to how these different velocities are combined
      into one unified and correct velocity. Neurons in area MT (V5) are considered to
      be the neural substrate for this motion integration process. Some MT neurons
      (pattern type) respond selectively to the correct global motion of an object,
      whereas others respond primarily to the individual components making up the
      pattern (component type). Recent findings from MT pattern cells tested with small
      patches of motion (N. J. Majaj, M. Carandini, & J. A. Movshon, 2007) have put
      further constraints on the possible mechanisms underlying MT pattern motion
      integration. We tested and refined an existing model of MT pattern neurons (J. A.
      Perrone, 2004) using these same small patch stimuli and found that it can
      accommodate these new findings. We also discovered that the speed of the test
      stimuli may have had an impact on the N. J. Majaj et al. (2007) results and that
      MT direction and speed tuning may be more closely linked than previously thought.

PMID- 18831638
TI  - Effects of attention on perceptual direction tuning curves in the human visual
      system.
AB  - In sensory neurophysiology, reverse correlation analyses have advanced our
      understanding of the spatio-temporal structure of receptive fields (RFs) and the
      tuning properties of individual neurons. Here, we used a psychophysical variant
      of the motion reverse correlation technique to investigate how visual selective
      attention influences human perceptual tuning curves for direction of motion.
      Direction tuning functions were computed by reverse correlating speeded target
      present responses of human observers with a random sequence of brief, fully
      coherent motion impulses. We found that attention enhanced the amplitude of
      perceptual tuning curves for direction of motion, while tuning width remained
      unaffected. Furthermore, the full direction tuning profile across time could be
      well fitted by a separable model of direction and temporal tuning. Attention
      enhanced both the direction tuning and its temporal profile, without shifts or
      changes in shape. Thus, attention exerts a multiplicative effect on human
      perceptual tuning curves for direction of motion. An analysis of second-order
      correlations revealed a boost in the likelihood of responses to the target
      direction when it was followed by a motion impulse in the opposite direction.
      This perceptual effect might be mediated by biphasic neurons that are
      preferentially activated by a rapid succession of opposite motion directions.

PMID- 18831639
TI  - Sensitivity to luminance and chromaticity gradients in a complex scene.
AB  - Image gradients--smooth changes in color and luminance--may be caused by
      intrinsic surface reflectance properties or extrinsic illumination phenomena,
      including shading, shadowing, and inter-reflections. In turn, image gradients may
      provide the visual system with information concerning the origin of these
      factors, such as the orientation of surfaces with respect to the light source.
      Color gradients induced by mutual illumination (MI) may play a similar role to
      that of luminance gradients in shape-from-shading algorithms; it has been shown
      that 3D shape perception modulates the influence of MI on surface color
      perception (M. G. Bloj, D. Kersten, & A. C. Hurlbert, 1999). In this study, we
      assess human sensitivity to changes in color and luminance gradients that arise
      from changes in the light source position, within a complex scene. In Experiment
      1, we tested whether observers were able to discriminate between gradients due to
      different light source positions. We found that observers reliably detected a
      change in the gradient information when the light source position differed by
      only 4 deg from the reference scene. This sensitivity was mainly based on the
      luminance information in the gradient (Experiments 2 and 3). Some observers make
      use of the spatial distribution of chromaticity and luminance values within
      gradients when discriminating between them (Experiment 4). The high sensitivity
      to gradient differences supports the notion that gradients contain information
      that may assist in the recovery of 3D shape and scene configuration properties.

PMID- 18831640
TI  - Some observations on contrast detection in noise.
AB  - The standard psychophysical model of our early visual system consists of a linear
      filter stage, followed by a nonlinearity and an internal noise source. If a
      rectification mechanism is introduced at the output of the linear filter stage,
      as has been suggested on some occasions, this model actually predicts that human
      performance in a classical contrast detection task might benefit from the
      addition of weak levels of noise. Here, this prediction was tested and confirmed
      in two contrast detection tasks. In Experiment 1, observers had to discriminate a
      low-contrast Gabor pattern from a blank. In Experiment 2, observers had to
      discriminate two low-contrast Gabor patterns identical on all dimensions, except
      for orientation (-45 degrees vs. +45 degrees). In both experiments, weak-to
      modest levels of 2-D, white noise were added to the stimuli. Detection thresholds
      vary nonmonotonically with noise power, i.e., some noise levels improve contrast
      detection performance. Both simple uncertainty reduction and an energy
      discrimination strategy can be excluded as possible explanations for this effect.
      We present a quantitative model consistent with the effects and discuss the
      implications.

PMID- 18831641
TI  - Serial correlations and 1/f power spectra in visual search reaction times.
AB  - In a visual search experiment, the subject must find a target item hidden in a
      display of other items, and their performance is measured by their reaction time
      (RT). Here I look at how visual search reaction times are correlated with past
      reaction times. Target-absent RTs (i.e. RTs to displays that have no target) are
      strongly correlated with past target-absent RTs and, treated as a time series,
      have a 1/f power spectrum. Target-present RTs, on the other hand, are effectively
      uncorrelated with past RTs. A model for visual search is presented which
      generates search RTs with this pattern of correlations and power spectra. In the
      model, search is conducted by matching search items up with "categorizers," which
      take a certain time to categorize each item as target or distractor; the RT is
      the sum of categorization times. The categorizers are drawn at random from a pool
      of active categorizers. After each search, some of the categorizers in the active
      pool are replaced with categorizers drawn from a larger population of unused
      categorizers. The categorizers that are not replaced are responsible for the RT
      correlations and the 1/f power spectrum.

PMID- 18831642
TI  - Crowding alters the spatial distribution of attention modulation in human primary
      visual cortex.
AB  - Crowding effect is the visibility reduction of a target when presented with
      neighboring distractors. It has been explained by either lateral inhibition at a
      pre-attentive level or coarse spatial resolution of attention. To test these
      theories, high-resolution fMRI was used to measure V1 response to the target in
      the presence or the absence of the distractors in both attended and unattended
      conditions. We found the cortical response to the target was not affected by the
      presence of distractors in the unattended condition. However, the spatial
      distribution of attention modulation in the target and its surrounding area
      depended on the crowding configuration. When distractors were placed in the same
      radial axis as the target, a configuration with a severe crowding effect,
      significant attention enhancements were observed not only in the target's and the
      distractors' locations, but also in regions next to the target where even no
      stimulus was presented. But this spread of attention enhancement did not occur
      when distractors were placed in the same circumference as the target, a
      configuration with a weak crowding effect. The pattern of interaction between
      attention and target-distractor configuration supports that crowding results from
      coarse spatial resolution of attention.

PMID- 18831643
TI  - Detecting and remembering pictures with and without visual noise.
AB  - Objects in a scene are often partially occluded without causing the viewer any
      problem: the occluded parts are apparently represented via amodal completion. To
      evaluate human ability to perceive and remember partially occluded pictures, we
      showed sequences of pictures using rapid serial visual presentation (RSVP) for
      durations of 53 ms, 107 ms, 213 ms, or 426 ms/picture. Participants either
      attempted to detect a named target (e.g., "businessmen at table") or were given a
      yes-no recognition memory test of one item. In Experiment 1, with as much as 30%
      of the picture area covered, detection and recognition were both well above
      chance. More interestingly, occlusion significantly affected recognition memory
      but not target detection. In Experiment 2, when pictures were inverted, occlusion
      impaired detection as severely as recognition. For target detection, the
      interaction between occlusion and inversion was significant. By contrast, taking
      away color information did not significantly reduce detection's tolerance of
      occlusion (Experiment 3). Finally, Experiment 4 showed that with 40% of the
      picture area occluded, detection performance was impaired. These results support
      the hypothesis that contextual gist information facilitates visual processes that
      tolerate occluding noise. Although inversion and color were tested in particular,
      the presented paradigm can also be used to investigate the role of other factors
      in gist representation.

PMID- 18831644
TI  - Figure-ground interaction in the human visual cortex.
AB  - Discontinuities in feature maps serve as important cues for the location of
      object boundaries. Here we used multi-input nonlinear analysis methods and EEG
      source imaging to assess the role of several different boundary cues in visual
      scene segmentation. Synthetic figure/ground displays portraying a circular figure
      region were defined solely by differences in the temporal frequency of the figure
      and background regions in the limiting case and by the addition of orientation or
      relative alignment cues in other cases. The use of distinct temporal frequencies
      made it possible to separately record responses arising from each region and to
      characterize the nature of nonlinear interactions between the two regions as
      measured in a set of retinotopically and functionally defined cortical areas.
      Figure/background interactions were prominent in retinotopic areas, and in an
      extra-striate region lying dorsal and anterior to area MT+. Figure/background
      interaction was greatly diminished by the elimination of orientation cues, the
      introduction of small gaps between the two regions, or by the presence of a
      constant second-order border between regions. Nonlinear figure/background
      interactions therefore carry spatially precise, time-locked information about the
      continuity/discontinuity of oriented texture fields. This information is widely
      distributed throughout occipital areas, including areas that do not display
      strong retinotopy.

PMID- 18831645
TI  - Effects of binocular suppression on surround suppression.
AB  - The responses of neurons in the primary visual cortex (V1) are generally
      inhibited by stimuli surrounding their classical receptive fields (CRF). This
      surround suppression can influence the visual perception of stimuli. For
      instance, the presence of a surround stimulus can decrease the apparent contrast
      of a central stimulus. A recent neurophysiological study in nonhuman primates
      suggests that two distinct mechanisms, early and late mechanisms, give rise to
      surround suppression. Here, we used binocular suppression to render the surround
      stimuli invisible and evaluated the effects of this masking on the two types of
      surround suppression. We found that the early mechanism was unsusceptible to,
      whereas the late mechanism was eliminated by, binocular suppression. The distinct
      effects of binocular suppression on the early and late mechanisms suggest that
      the two types of surround suppression arise from different neural substrates.

PMID- 18831646
TI  - Cortical correlates of stereoscopic depth produced by temporal delay.
AB  - Stereoscopic depth processing for static objects depends on retinal disparities
      between the two eyes and has been shown in previous functional imaging (fMRI)
      work to involve widely distributed activity in the human visual cortex, including
      both dorsal and ventral streams. Stereoscopic depth processing of moving objects,
      on the other hand, can be produced by purely temporal lags between the eyes, and
      the cortical basis for this kind of stereopsis has received less attention. Using
      fMRI in human subjects, we measured the activations produced by dynamic visual
      noise both when it was in phase between the eyes and appeared two-dimensional
      (2D) and when an interocular delay made it appear like a 3D rotating cylinder.
      When observers attended to the depth, the stimulus with the interocular delay
      produced more activity than the 2D stimulus in a large variety of cortical areas,
      including V1, V3A, caudal intraparietal sulcus (cIPS), and MT. When, on the other
      hand, observers attended to a digit counting task in the fovea, the stimulus with
      the interocular delay tended to decrease the BOLD response in V1 while still
      increasing it significantly in area cIPS. The areas that are activated by
      interocular delay even when not attending to depth (MT, cIPS) are similar to
      those previously described for traditional stereoscopic stimuli, and we conclude
      that the dorsal-stream mechanisms for processing interocular delay are not
      different at the level of spatial resolution of this study.

PMID- 18831647
TI  - Relationships between versional and vergent quick phases of the involuntary
      version-vergence nystagmus.
AB  - We used ground-plane motion stimuli displayed on a computer monitor positioned
      below eye level to induce involuntary version-vergence nystagmus (VVN). The VVN
      was recorded with a search coil system. It was shown that the VVN had both
      vertical versional and horizontal vergence components. The VVN induced by
      backward motion (toward subjects) had upward versional and divergence quick
      phases, whereas those induced by forward motion (away from subjects) had downward
      and biphasic divergence-convergence quick phases. The versional and vergence
      components of the VVN quick phases were analyzed. A temporal dissociation of
      about 20 ms between version velocity peak and convergence velocity peak was
      revealed, which supported a modified saccade-related vergence burst neuron (SVBN)
      model. We suggest that the temporal dissociation may be partly because of a lower
      level OKN control mechanism. Vergence peak time was dependent on version peak
      time. Linear relationships between vergence peak velocity and versional saccadic
      peak velocity were demonstrated, which was in line with the new multiplicative
      model. Our data support the hypothesis that the vergence system and the saccadic
      system can act separately but interact with each other whenever their movements
      occur simultaneously.

PMID- 18831648
TI  - Disorganizing biological motion.
AB  - The rapid and seemingly effortless organization of visually impoverished point
      light displays of humans walking is often held up as a compelling example of the
      perception of form from motion. Here we show that motion information is not
      sufficient for the impression of a human walker to be extracted from a point
      light display. We manipulated the 13 small dots out of which the typical point
      light walker is constructed. Attempts to use size, color, or shape changes to
      disrupt walker perception had only modest impact on its robustness. But when all
      the local elements of the walker were replaced with complex unique objects,
      perception of the walker was severely disrupted. Of seventy-seven naive observers
      presented with this array for one full gait cycle, none perceived a human walker,
      even though movement paths were unchanged. We conclude that the spontaneous
      perception of a human walking is not an inevitable consequence of the motion of
      the points in a point-light walker but depends on the points themselves being
      relatively simple and uniform.

PMID- 18831649
TI  - Metrics of the perception of body movement.
AB  - Body movements are recognized with speed and precision, even from strongly
      impoverished stimuli. While cortical structures involved in biological motion
      recognition have been identified, the nature of the underlying perceptual
      representation remains largely unknown. We show that visual representations of
      complex body movements are characterized by perceptual spaces with well-defined
      metric properties. By multidimensional scaling, we reconstructed from similarity
      judgments the perceptual space configurations of stimulus sets generated by
      motion morphing. These configurations resemble the true stimulus configurations
      in the space of morphing weights. In addition, we found an even higher similarity
      between the perceptual metrics and the metrics of a physical space that was
      defined by distance measures between joint trajectories, which compute spatial
      trajectory differences after time alignment using a robust error norm. These
      outcomes were independent of the experimental paradigm for the assessment of
      perceived similarity (pairs-comparison vs. delayed match-to-sample) and of the
      method of stimulus presentation (point-light stimuli vs. stick figures). Our
      findings suggest that the visual perception of body motion is veridical and
      closely reflects physical similarities between joint trajectories. This implies
      that representations of form and motion share fundamental properties and places
      constraints on the computational mechanisms that support the recognition of
      biological motion patterns.

PMID- 18831650
TI  - Facilitation of multisensory integration by the "unity effect" reveals that
      speech is special.
AB  - Whenever two or more sensory inputs are highly consistent in one or more
      dimension(s), observers will be more likely to perceive them as a single
      multisensory event rather than as separate unimodal events. For audiovisual
      speech, but not for other noncommunicative events, participants exhibit a "unity
      effect," whereby they are less sensitive to temporal asynchrony (i.e., that are
      more likely to bind the multisensory signals together) for matched (than for
      mismatched) speech events. This finding suggests that the modulation of
      multisensory integration by the unity effect in humans may be specific to speech.
      To test this hypothesis directly, we investigated whether the unity effect would
      also influence the multisensory integration of vocalizations from another primate
      species, the rhesus monkey. Human participants made temporal order judgments for
      both matched and mismatched audiovisual stimuli presented at a range of stimulus
      onset asynchronies. The unity effect was examined with (1) a single call-type
      across two different monkeys, (2) two different call-types from the same monkey,
      (3) human versus monkey "cooing," and (4) speech sounds produced by a male and a
      female human. The results show that the unity effect only influenced
      participants' performance for the speech stimuli; no effect was observed for
      monkey vocalizations or for the human imitations of monkey calls. These findings
      suggest that the facilitation of multisensory integration by the unity effect is
      specific to human speech signals.

PMID- 18831651
TI  - ConTrack: finding the most likely pathways between brain regions using diffusion
      tractography.
AB  - Magnetic resonance diffusion-weighted imaging coupled with fiber tractography
      (DFT) is the only non-invasive method for measuring white matter pathways in the
      living human brain. DFT is often used to discover new pathways. But there are
      also many applications, particularly in visual neuroscience, in which we are
      confident that two brain regions are connected, and we wish to find the most
      likely pathway forming the connection. In several cases, current DFT algorithms
      fail to find these candidate pathways. To overcome this limitation, we have
      developed a probabilistic DFT algorithm (ConTrack) that identifies the most
      likely pathways between two regions. We introduce the algorithm in three parts: a
      sampler to generate a large set of potential pathways, a scoring algorithm that
      measures the likelihood of a pathway, and an inferential step to identify the
      most likely pathways connecting two regions. In a series of experiments using
      human data, we show that ConTrack estimates known pathways at positions that are
      consistent with those found using a high quality deterministic algorithm. Further
      we show that separating sampling and scoring enables ConTrack to identify valid
      pathways, known to exist, that are missed by other deterministic and
      probabilistic DFT algorithms.

PMID- 18831652
TI  - Masking exposes multiple global form mechanisms.
AB  - Previous work suggests there are mechanisms at intermediate levels of visual
      processing specialized for the detection of radial and circular form. The
      evidence in favor of specialized global form mechanisms is derived from structure
      detection experiments that have told us very little about their bandwidth or
      number. To address these related questions, we examined the effects of configural
      backward masking on human observers' ability to detect global structure in arrays
      with different spiral forms. Each array consisted of 100 Gabors randomly
      positioned within a circular annular window. Observers judged which of two
      sequentially presented Gabor arrays contained global structure. One array
      contained Gabors with random orientations; the other contained Gabors with a
      variable proportion of orientations coherent with a randomly chosen spiral pitch.
      At its offset, each array was immediately followed by a backward masking Gabor
      array with a fixed spiral pitch angle. When mask and test had the same spiral
      pitch, we found an approximately three-fold elevation of structure detection
      thresholds that was not explained by local orientation masking. The magnitude and
      breadth of tuning around each masking angle was predicted by a simple model
      consisting of at least eight detectors broadly tuned for different spiral forms.

PMID- 18831653
TI  - Variability in access to hospital palliative care in the United States.
AB  - BACKGROUND: Hospital palliative care programs provide high-quality, comprehensive
      care for seriously ill patients and their families. OBJECTIVE: To examine
      geographic variation in patient and medical trainee access to hospital palliative
      care and to examine predictors of these programs. METHODS: Primary and secondary
      analyses of national survey and census data. Hospital data including hospital
      palliative care programs were obtained from the American Hospital Association
      (AHA) Annual Survey Databasetrade mark for fiscal year 2006 supplemented by
      mailed surveys. Medical school-affiliated hospitals were obtained from the
      American Association of Medical Colleges, Web-site review, and telephone survey.
      Health care utilization data were obtained from the Dartmouth Atlas of Health
      Care 2008. Multivariate logistic regression was used to identify characteristics
      significantly associated with the presence of hospital palliative care. RESULTS:
      A total of 52.8% of hospitals with 50 or more total facility beds reported
      hospital palliative care with considerable variation by state; 40.9% (144/352) of
      public hospitals, 20.3% (84/413) of for-profit hospitals, and 28.8% (160/554) of
      Medicare sole community providers reported hospital palliative care. A total of
      84.5% of medical schools were associated with at least one hospital palliative
      care program. Factors significantly associated (p < 0.05) with hospital
      palliative care included geographic location, owning a hospice program, having an
      American College of Surgery approved cancer program, percent of persons in the
      county with a university education, and medical school affiliation. For-profit
      and public hospitals were significantly less likely to have hospital palliative
      care when compared with nonprofit institutions. States with higher hospital
      palliative care penetration rates were observed to have fewer Medicare hospital
      deaths, fewer intensive care unit/cardiac care unit (ICU/CCU) days and admissions
      during the last 6 months of life, fewer ICU/CCU admission during terminal
      hospitalizations, and lower overall Medicare spending/enrollee. DISCUSSION: This
      study represents the most recent estimate to date of the prevalence of hospital
      palliative care in the United States. There is wide geographic variation in
      access to palliative care services although factors predicting hospital
      palliative care have not changed since 2005. Overall, medical students have high
      rates of access to hospital palliative care although complete penetration into
      academic settings has not occurred. The association between hospital palliative
      care penetration and lower Medicare costs is intriguing and deserving of further
      study.

PMID- 18831654
TI  - Transcavum interforniceal endoscopic surgery of the third ventricle.
AB  - OBJECT: Intraventricular anatomy has been detailed as it pertains to endoscopic
      surgery within the third ventricle, particularly for performing endoscopic third
      ventriculostomy (ETV) and endoscopic colloid cyst resection. The expanding role
      of endoscopic surgery warrants a careful appraisal of these techniques as they
      relate to frequent anatomical variants. Given the common occurrence of cavum
      septum pellucidum (CSP) and cavum vergae (CV), the endoscopic surgeon should be
      familiar with that particular anatomy especially as it pertains to surgery within
      the third ventricle. METHODS: From a prospective database of endoscopic surgical
      cases were selected those cases in which the defined pathology necessitated
      surgery within the third ventricle and there was coexistent CSP and CV. Pertinent
      radiographic studies, operative notes, and archived video files were reviewed to
      define the relevant anatomy. Features of the intracavitary anatomy were assessed
      regarding their importance in approaching the third ventricle. RESULTS: Four
      cases involving endoscopic surgery within the third ventricle (2 colloid cyst
      resections and 2 ETVs) were identified in which the surgical objective was
      accomplished through a septal cavum. In each case the width of the body of the
      lateral ventricle was reduced and the foramen of Monro was obscured. Because of
      the ventricular distortion, a stereotactic transcavum route was used for
      approaching the third ventricle. Entry into the third ventricle was accomplished
      through an interforniceal fenestration immediately behind the anterior
      commissure. The surgical goal was met in each case without any neurological
      change or postoperative morbidity. During the follow-up period, there has been no
      recurrence of a colloid cyst and no need of a secondary cerebrospinal fluid
      diversionary procedure. CONCLUSIONS: In the presence of a CSP and CV, endoscopic
      navigation into the third ventricle can be problematic via a transforaminal
      approach. Alternatively, a transcavum interforniceal route for endoscopic surgery
      in the third ventricle is suggested, with the rostral lamina and the anterior
      commissure as important anatomical landmarks. Endoscopic third ventriculostomy
      and endoscopic colloid cyst resection performed via a transcavum interforniceal
      route in patients with a coexistent septal cavum is a feasible and safe option.

PMID- 18831655
TI  - Pediatric traumatic brain injury and elevated intracranial pressure.

PMID- 18831656
TI  - Long-term outcomes and prognostic factors in pediatric patients with severe
      traumatic brain injury and elevated intracranial pressure.
AB  - OBJECT: The management strategies and outcomes in pediatric patients with
      elevated intracranial pressure (ICP) following severe traumatic brain injury
      (TBI) are examined in this study. METHODS: This study was a retrospective review
      of a prospectively acquired pediatric trauma database. More than 750 pediatric
      patients with brain injury were seen over a 10-year period. Records were
      retrospectively reviewed to determine interventions for correcting ICP, and
      surviving patients were contacted prospectively to determine functional status
      and quality of life. Only patients with 2 years of follow-up were included in the
      study. RESULTS: Ninety-six pediatric patients (age range 3-18 years) were
      identified with a Glasgow Coma Scale score<8 and elevated ICP>20 mm Hg on
      presentation. The mean injury severity score was 65 (range 30-100). All patients
      were treated using a standardized head injury protocol. The mean time course
      until peak ICP was 69 hours postinjury (range 2-196 hours). Intracranial pressure
      control was achieved in 82 patients (85%). Methods employed to achieve ICP
      control included maximal medical therapy (sedation, hyperosmolar therapy, and
      paralysis) in 34 patients (35%), ventriculostomy in 23 patients (24%), and
      surgery in 39 patients (41%). Fourteen patients (15%) had refractory ICP despite
      all interventions, and all of these patients died. Seventy-two patients (75%)
      were discharged from the hospital, whereas 24 (25%) died during hospitalization.
      Univariate and multivariate analysis revealed that the presence of vascular
      injury, refractory ICP, and cisternal effacement at presentation had the highest
      correlation with subsequent death (p<0.05). Mean follow-up was 53 months (range
      11-126 months). Three patients died during the follow-up period (2 due to
      infections and 1 committed suicide). The mean 2-year Glasgow Outcome Scale score
      was 4 (median 4, range 1-5). The mean patient competency rating at follow-up was
      4.13 out of 5 (median 4.5, range 1-4.8). Univariate analysis revealed that the
      extent of intracranial and systemic injuries had the highest correlation with
      long-term quality of life (p<0.05). CONCLUSIONS: Controlling elevated ICP is an
      important factor in patient survival following severe pediatric TBI. The modality
      used for ICP control appears to be less important. Long-term follow-up is
      essential to determine neurocognitive sequelae associated with TBI.

PMID- 18831657
TI  - Incomplete lateral medullary syndrome in a patient with Chiari malformation Type
      I presenting with combined trigeminal and vagal nerve dysfunction.
AB  - The combination of unilateral trigeminal and vagal nerve dysfunction is a rare
      presentation in patients with Chiari malformation Type I (CM-I). The authors
      present a case of incomplete lateral medullary syndrome in a patient with CM-I.
      The patient's symptoms of decreased unilateral facial sensitivity to pain and
      temperature and her vocal cord dysfunction reversed after posterior fossa
      decompression and intradural exploration. Although rare, clinicians should be
      aware of this presentation as part of a protean spectrum of symptoms in patients
      with CM-I.

PMID- 18831658
TI  - Clinical predictors of developmental outcome in patients with cephaloceles.
AB  - OBJECT: Cephaloceles represent primary axial mesodermal defects, occurring in 0.8
      4 per 10,000 live births. Prior studies have reported posterior location,
      hydrocephalus, microcephaly, seizure, and presence of brain tissue as poor
      prognostic markers for neurological outcome. However, these studies were small
      and the results were analyzed using univariate tests. The purpose of this study
      was to investigate the potential risk factors for the occurrence of developmental
      delay in patients with cephaloceles, using both univariate and multivariable
      regression techniques. METHODS: This is a retrospective cohort study of
      cephalocele cases treated at the Hospital for Sick Children between 1990 and
      2006. Two independent investigators collected the data from the Hospital for Sick
      Children Encephalocele Database and hospital charts. Developmental assessments
      were made by general pediatricians and neuropsychologists. Both univariate
      analysis (alpha=0.10) and multivariable logistic regression analysis (alpha=0.05)
      were performed. RESULTS: Eighty-five cases of cephaloceles were identified. The
      patient group consisted of 48 boys and 37 girls. Sixty-eight lesions were
      encephaloceles and 17 were meningoceles. The distribution was as follows: frontal
      (40 lesions), occipital (33), and parietal (12). Associated conditions included
      hydrocephalus (23), seizure disorder (17), microcephaly (6), corpus callosal
      abnormalities (15), heterotopias (9), cerebral dysgenesis (11), and
      myelomeningocele (1). Evaluation of long-term development revealed that 41
      patients (48%) had normal development, 9 (11%) had mild delay, 14 (16%) had
      moderate delay, and 21 (25%) had severe delay. Hydrocephalus, seizure disorder,
      microcephaly, presence of associated intracranial abnormalities, and presence of
      brain tissue were significantly associated with poor outcome on univariate
      analysis. Multivariable analysis revealed hydrocephalus and presence of
      intracranial abnormalities to be statistically significant predictors of
      developmental delay. CONCLUSIONS: To the authors' knowledge, this is one of the
      largest North American cephalocele series documented. Unlike prior studies,
      location of the cephaloceles is not a significant predictor of outcome. The
      multivariable regression analysis demonstrates hydrocephalus and the presence of
      associated intracranial abnormalities as variables with cumulative predictive
      effects for developmental delay.

PMID- 18831659
TI  - Spina bifida occulta and monozygotic twins.
AB  - Central nervous system maldevelopment can have different presentations in twins.
      We report on a case of different presentations of spina bifida occulta in
      monozygotic twins. The first twin presented at birth with a lipomyelomeningocele;
      a tethered cord was diagnosed in the second twin at 2 years of age. Neural tube
      defects (NTDs) are a group of common congenital malformations of the brain and
      spine generated during neurulation. The genetic basis of this process is still
      not well known. Whenever an NTD is diagnosed in one of a pair of twins, the other
      twin should also be evaluated for NTDs.

PMID- 18831660
TI  - Expanded endoscopic endonasal resection of an olfactory schwannoma.
AB  - Olfactory schwannomas are rare tumors of the anterior skull base that are
      possibly derived from ectopic Schwann cells, perivascular neural tissue, or
      sensory nerves of the meninges. The authors report the case of a 14-year-old boy
      with an olfactory schwannoma that extended inferiorly through the cranial base
      and superiorly into the frontal lobe. Because of the growth characteristics of
      the tumor and the significant overlying frontal lobe edema, the lesion was
      approached via an endonasal endoscopic route, as a strategy to minimize brain
      retraction. This tumor was characterized radiographically as contrast-enhancing
      with cystic areas and erosion into bone. The tumor showed immunoreactivity for
      S100 protein and leukocyte antigen 7 (CD57) but not epithelial membrane antigen,
      supporting the diagnosis of olfactory schwannoma. A gross-total resection was
      achieved. This approach represents a novel application of endoscopic endonasal
      surgery to the pediatric neurosurgical context, as well as a favorable outcome in
      an extremely unusual tumor type, that should be applicable to other appropriately
      selected pediatric brain tumors.

PMID- 18831661
TI  - Frontal intradiploic angioleiomyoma.
AB  - A left frontal intradiploic angioleiomyoma in a 10-year-old girl is presented
      with a review of the literature. The pathological and differential diagnosis and
      management of this rare lesion is discussed.

PMID- 18831662
TI  - Third ventricular chordoid meningioma in a child.
AB  - Meningiomas are rare in children. Chordoid meningioma is a very rare variant, as
      only 16 cases in children have been reported. The authors report the first case
      of a chordoid meningioma in the third ventricle. A 12-year-old boy presented with
      headache, abnormal behaviors, and ataxia. Brain MR imaging revealed a 2-cm, well
      enhanced mass in the third ventricle and hydrocephalus. Positron emission
      tomography with [18F]fluorodeoxyglucose showed that the mass was hypermetabolic.
      Gross-total removal of the mass was performed using a left frontal transcortical
      and transventricular approach. The mass originated from the left caudate head and
      was connected to the choroid plexus. A chordoid meningioma was diagnosed on the
      basis of the histological characteristics of the tumor, which was composed of
      cords and nests of eosinophilic vacuolated cells with an abundant myxoid matrix,
      similar to the features of a chordoma. A typical focal meningiomatous pattern was
      observed. The tumor cells were immunoreactive for vimentin and epithelial
      membrane antigen. The patient's headache and gait disturbance improved after the
      tumor was removed. The tumor showed no signs of recurrence during 12 months of
      follow-up.

PMID- 18831663
TI  - Lymphangioma of the skull base bones leading to cerebrospinal fluid rhinorrhea.
AB  - Lymphangioma localized to the bones of the skull base is rare. The authors report
      herein the case of a 5-year-old boy who presented with lymphangioma of the bone,
      localized to the skull base and leading to cerebrospinal fluid (CSF) rhinorrhea
      with meningitis. Neuroimaging demonstrated lytic destruction with a cyst in the
      right middle skull base. The patient was successfully treated with resection of
      the tumor and prevention of CSF leakage. Histopathological examination revealed a
      lymphangioma. An enlarging lymphangioma can lead to bone destruction. A
      differential diagnosis of a lytic lesion for a cyst at the skull base is
      important for proper case management.

PMID- 18831664
TI  - Correlation of a preoperative grading scale with progressive spinal deformity
      following surgery for intramedullary spinal cord tumors in children.
AB  - OBJECT: Postoperative progressive spinal deformity often complicates functional
      outcome after resection of pediatric intramedullary spinal cord tumors (IMSCTs).
      The authors propose a preoperative grading scale that correlates with the
      postoperative development of progressive spinal deformity requiring subsequent
      fusion. METHODS: The data obtained in 164 patients who underwent resection of an
      IMSCT at a single institution were retrospectively collected and analyzed to
      determine the development of progressive spinal deformity requiring fusion. A
      grading scale (range of scores I-V) was created based on the presence or absence
      of 4 preoperative variables: preoperative scoliosis, involvement of the
      thorocolumbar junction, age<13 years, and number of surgeries for an IMSCT. The
      grading scale was then retrospectively applied to this series of 164 children to
      assess the correlation of variables with subsequent spinal deformity. RESULTS:
      Nine patients presented with Grade I status, 41 patients with Grade II, 58
      patients with Grade III, 44 patients with Grade IV, and 12 patients with Grade V.
      Overall, 44 patients (27%) developed progressive spinal deformity requiring
      fusion at a mean follow-up of 5 years after surgery. A higher preoperative grade
      was associated with an increasing need for subsequent fusion for progressive
      spinal deformity (Grade I [0%], Grade II [5%], Grade III [26%], Grade IV [40%],
      and Grade V status [75%]). CONCLUSIONS: Application of this grading scheme to a
      series of resected pediatric IMSCTs has demonstrated its correlation with the
      incidence of postoperative progressive spinal deformity requiring fusion. The
      application of a standardized grading scheme will assist in the process of
      surgical decision making and postoperative evaluation.

PMID- 18831665
TI  - Laparoscopic placement of distal ventriculoperitoneal shunt catheters.
AB  - OBJECT: Ventriculoperitoneal shunts (VPSs) are commonly placed into the
      peritoneal cavity via a small laparotomy or blindly by using a split trocar.
      Larger patients require larger incisions, and placement is made more difficult by
      previous abdominal operations and obesity. For general surgeons, laparoscopy has
      become the first-choice approach for abdominal procedures, using 1 or several
      very small incisions. The authors discuss their pediatric series of patients in
      whom laparoscopy was used to place distal shunt catheters. METHODS: The authors
      reviewed the medical records accrued over a 9-year period, noting VPS operations
      performed using laparoscopy. Complications, morbidity, and alterations of planned
      management were noted. RESULTS: One hundred thirty-seven VPS operations in 126
      patients were identified, 92 performed by the senior author (M.H.H.) alone and 45
      conducted with the assistance of a general surgeon. A second port was placed for
      lysis of adhesions or retrieval of old catheters in 7 cases. There were no
      immediate complications. The infection rate was 6.6%, comparable with the
      institutional norm (6.3%) over an 8-year period. There were 3 early failures due
      to abdominal malabsorption without infection. Five catheters later broke at the
      level where they were introduced into the abdomen due to shearing by the
      abdominal trocar. CONCLUSIONS: Laparoscopic placement of distal VPS catheters is
      relatively safe and allows insertion via inconspicuous incisions. It can allow
      for inspection or lysis of adhesions and removal of foreign bodies, help
      determine if and where the abdomen can absorb shunt fluid, and make VPS surgery
      in the obese patient easier.

PMID- 18831666
TI  - Thrombosis associated with ventriculoatrial shunts.
AB  - OBJECT: In this single-center study, the authors examined the clinical
      characteristics, risk factors, treatment strategies, and outcomes in patients
      with thrombosis associated with ventriculoatrial (VA) shunts. METHODS: Inpatient
      and outpatient charts of patients who underwent treatment and follow-up in the
      Hematology-Oncology Division at the authors' institution and in whom thrombosis
      developed secondary to a VA shunt placement were reviewed. A complete
      thrombophilia work-up was performed in each patient, and these records were also
      reviewed. Treatment including medical and surgical management was noted and
      outcome data were recorded. RESULTS: Resolution of thrombosis was seen after
      anticoagulation therapy in all patients; this may be an alternative to surgical
      therapy. CONCLUSIONS: Patients with VA shunts represent a unique group at risk
      for thrombosis. The duration of anticoagulation therapy must be individualized.
      However, larger studies are needed to evaluate the efficacy of screening for
      asymptomatic thrombosis and to investigate the role of prophylactic
      anticoagulation.

PMID- 18831667
TI  - Ultrasound guidance.

PMID- 18831668
TI  - Shunt infection.

PMID- 18831670
TI  - A comparison of the physical properties of four new generation flexible
      ureteroscopes: (de)flection, flow properties, torsion stiffness, and optical
      characteristics.
AB  - BACKGROUND AND PURPOSE: Several kinds of flexible ureteroscopes are in use for
      the removal of kidney stones. This study evaluated and compared the
      characteristics of four new-generation flexible ureteroscopes. MATERIALS AND
      METHODS: The flexible ureteroscopes studied were: the ACMI Dur-8 Elite, the Storz
      Flex-X2 the Olympus XURF-P5, and the Wolf 7325.076. Measured properties included
      (de)flection, instrument insertion, flow properties, torsion stiffness, and
      optical characteristics. Active tip deflection and irrigation flow rates with and
      without various endoscopic tools were assessed. RESULTS: All ureteroscopes score
      better on (de)flection with an empty working channel, compared with a channel
      when tools are inserted (differences minimum 0.3 degrees--maximum 80.6 degrees).
      The Olympus XURF-P5 is the only ureteroscope with passive (de)flection
      capability, whereas the ACMI DUR-8 Elite is the only ureteroscope that has a
      secondary active (de)flection capability. The Storz Flex-X2 and the Wolf 7325.076
      ureteroscopes show nearly identical best deflection capabilities with and without
      tools inserted in the working channel. The longest (Olympus XURF-P5, 70 cm) and
      shortest (ACMI DUR-8 Elite, 64 cm) ureteroscopes have, respectively, the lowest
      and highest flow rates. Best optical quality is offered by the Olympus XURF-P5
      and Wolf 7325.076 ureteroscopes, which have low optical distortion (-9.7; -7.7%),
      high resolving power (17.95; 16.00 line pairs per millimeter), and a large field
      of view (62.9; 63.2 degrees). The Storz Flex-X2 and Wolf 7325.076 ureteroscopes
      have lowest torsion stiffness. CONCLUSIONS: The ex vivo evaluation of the
      deflection capabilities, passage of instruments, flow properties, torsion
      stiffness, and optical characteristics yielded quantitative measures of the in
      vivo performance capabilities of four new-generation flexible ureteroscopes. New
      ureteroscopes should be subjected to this or similar evaluation and comparison.
      Only in this way can the urologist make an informed and objective decision
      regarding appropriate instrument choice.

PMID- 18831671
TI  - Treatment of patients after failed high intensity focused ultrasound and
      radiotherapy for localized prostate cancer: salvage laparoscopic extraperitoneal
      radical prostatectomy.
AB  - INTRODUCTION: To evaluate the feasibility and efficacy of salvage endoscopic
      extraperitoneal radical prostatectomy (EERPE) in recurrent prostate cancer after
      failed high intensity focused ultrasound therapy (HIFU), external beam
      radiotherapy (EBT) and brachytherapy. PATIENTS AND METHODS: Twelve patients with
      mean age 63.3 years (48-74), mean preoperative PSA 12.7 ng/ml and mean prostate
      weight 48.8 grams were treated with salvage EERPE with curative intent for biopsy
      proven locally recurrent prostate cancer. Our group was consisted of four
      patients who have been treated in the past with HIFU, six with EBT and two with
      brachytherapy. Operative time, estimated blood loss, conversion to open surgery
      rate, transfusion rate and transurethral catheter time were recorded. Also
      functional outcome and short term oncological outcome were reviewed. RESULTS:
      Average operative time was 153 minutes. Mean blood loss was 238 ml. The procedure
      was completed in all cases with no difficulty and without intraoperative
      complications. There was no need for conversion to open surgery or transfusion.
      Mean total urethral catheterization time was 7.2 days. After mean follow-up of 20
      months, 10 patients were completely continent, and 2 needed 1-2 pads per day.
      Three patients were potent before the surgical treatment, but no one reported
      potency postoperatively. Biochemical recurrence was observed in only one patient
      12 months postoperatively. DISCUSSION: In the initial experience, salvage EERPE
      in experienced hands has minimal perioperative morbidity. Short term oncological
      and functional outcomes are encouraging but further studies and longer follow-up
      are required in order to assess the long-term outcomes.

PMID- 18831672
TI  - Concomitant percutaneous nephrolithotomy and transperitoneal laparoscopic
      pyeloplasty for ureteropelvic junction obstruction complicated by stones.
AB  - INTRODUCTION: Ureteropelvic junction (UPJ) obstruction and stones can co exist.
      Therapeutic controversy exists regarding their ideal management. We present our
      experience of combining Percutaneous nephrolithotomy (PNL) with laparoscopic
      pyeloplasty (LP),in patients with UPJ obstruction with multiple secondary, in the
      same session or staged manner. PATIENTS AND METHOD: From November 2006 till April
      2008 ten patients underwent PNL with LP at our institution. Two of these patients
      had recurrent obstruction and stones after PNL and endopyelotomy. All patients
      had multiple calyceal and pelvic calculi (>10) with sizes ranging from 3 to 24
      mm. Mean age of patients was 33 years (17-55). PNL was done in standard manner
      and was followed by laparoscopic pyeloplasty. RESULT: Complete stone clearance
      could be achieved in all by PNL. Procedure was staged in 2 due to the presence of
      infected hydronephrosis. 9 patients underwent dismembered pyeloplasty and in 1
      Fengerplasty was done. Reduction of baggy pelvis was required in 3 cases. Mean
      operative time was 3. 9 hours (3-5). Postoperatively the nephrostomy was kept for
      an average of 2 days (1-3). Drain was removed after an average of 3. 5 days (3
      5). Mean hospital stay was 5. 2 days (5-7). None of the patients required blood
      transfusion. Stent was removed after 4 weeks. At 6 months patients are stone free
      on ultrasound and show good drainage on renal scan. One year follow-up is
      available for 5 patients which shows a stone free status and good drainage across
      UPJ. CONCLUSION: Concomitant PNL and laparoscopic pyeloplasty are feasible and
      safe for patients with UPJ obstruction complicated by multiple calculi. We did
      not encounter any intraoperative difficulty during pyeloplasty following PNL.

PMID- 18831673
TI  - Prospective comparison of four laparoscopic vessel ligation devices.
AB  - PURPOSE: The merits of laparoscopic sealing devices have been poorly
      characterized. The purpose of this study was to compare two bipolar sealing
      devices [LigaSure V (LS) and Gyrus PK (GP)], an ultrasonic device [Harmonic
      Scalpel ACE (HS)] and a novel device using nanotechnology [EnSeal PTC (ES)].
      MATERIALS AND METHODS: The ability of all four 5 mm devices to seal 5 mm bovine
      arteries was tested under controlled temperature and humidity in accordance with
      manufacturer specifications. Study endpoints included lateral thermal spread,
      time to seal, burst pressure, smoke production and subjective (blinded review of
      video clips) and objective (measured using an aerosol monitor) effect upon
      visibility. RESULTS: The HS demonstrated the least thermal spread. The LS (10.0
      secs) and GP (11.1 secs) had the fastest sealing times (p<0.001 for both) when
      compared to ES (19.2 sec) and HS (14.3 sec). Mean burst pressure values were: LS
      385 mm Hg, GP 290 mm Hg, ES 255 mm Hg and HS 204 mm Hg. The HS had the best
      subjective visibility score and the lowest objective smoke production (2.88 ppm)
      compared to the GP (74.1 ppm), ES (21.6 ppm) and LS (12.5 ppm), (p<0.01 for all).
      CONCLUSIONS: The LS has the highest burst pressure and fastest sealing time and
      was the highest rated overall. The HS produced the lowest thermal spread and
      smoke but had the lowest mean burst pressure. The GP had the highest smoke
      production, and variable burst pressures. Despite employing nanotechnology, the
      ES device was the slowest and had variable burst pressures.

PMID- 18831674
TI  - Laparoscopic donor nephrectomy: effect of perirenal fat upon donor operative
      time.
AB  - PURPOSE: Previous attempts to correlate preoperative patient characteristics with
      operative complexity and operative time prior to laparoscopic donor nephrectomy
      have found few consistent relationships. The purpose of this study is to
      determine the effect of abdominal and perirenal fat measured with preoperative
      computerized tomography (CT) upon subsequent operative time and complexity during
      hand-assisted laparoscopic donor nephrectomy. MATERIALS AND METHODS: A
      retrospective chart, database, and CT angiogram review was conducted on 103
      consecutive patients who underwent a hand-assisted laparoscopic donor
      nephrectomy. Perirenal fat and abdominal wall fat were correlated with a variety
      of parameters including operative time. Univariate and multivariate regression
      analysis was performed and p values<0.05 were considered significant. RESULTS:
      There was no correlation between operative time and body mass index (BMI),
      abdominal fat measurements, or spleno-renal distance. There was a significant
      positive correlation between operative time and anterior perirenal fat (r=0.28,
      p=0.005), posterior perirenal fat (r=0.20, p=0.05), and donor CPK levels (r=0.53,
      p<0.001). Men had greater perirenal fat, while women had greater abdominal fat. A
      multivariate model including anterior perirenal fat measurement accounted for 20%
      of the variance in operative time. CONCLUSION: This is the first study to
      demonstrate that increased perirenal fat increases operative complexity as
      measured by operative time. This information may potentially be used to help
      predict operative complexity based upon measurable preoperative variables and
      help improve operating room efficiency and donor and recipient outcomes.

PMID- 18831675
TI  - Endoscopic extraperitoneal radical prostatectomy: the University of Leipzig
      experience of 2000 cases.
AB  - INTRODUCTION: Review of experience with endoscopic extraperitoneal radical
      prostatectomy (EERPE) for localized prostate cancer. PATIENTS AND METHODS: 2000
      patients underwent EERPE. Mean age of the patients was 63.2 (41-77) years. Mean
      preoperative PSA was 10.2 ng/ml (0.64-82 ng/ml). 601 patients had undergone
      previous surgery. The functional and oncological outcomes were reviewed. RESULTS:
      Mean operation time was 156 (50-320) min. Complication rate according to Clavien
      system was: 0.45% intraoperatively, 8.6% in the early and 0.3% in the late
      postoperative period. Positive surgical margins were found in 127 patients with
      pT2 stage (9.7%) and in 237 patients with pT3 stage (34.4%). 44/937
      lymphadenectomies (4.7%) had positive lymph nodes. Mean catheterization time was
      6.3 days. After 12 months, 92% of the patients were completely continent, 7%
      needed 1-2 pads/day and 1% used more than 2 pads daily.730 patients underwent
      nerve sparing procedure. The 12 month potency rates with or without
      administration of PDE 5 inhibitors were 34.1% in the unilateral nerve sparing
      group and 67.7% in the bilateral group. In the intrafascial nsEERPE group, after
      12 months, 93.2% of the patients were completely continent, 7.1% required 1-2
      pads per day and 0.6% more than 2 pads per day. Twelve months potency rate for
      unilateral and bilateral nerve sparing intrafascial procedure was 33.3% and 78.5
      % respectively. The rate of positive surgical margins was 6.3% in pT2 and 21.2%
      in pT3 specimens. DISCUSSION: Functional and oncological results of this large
      series are promising. The recently introduced intrafascial nsEERPE further
      improves the outcome of the procedure.

PMID- 18831676
TI  - Differences in computed tomography density of the renal papillae of stone formers
      and non-stone-formers: a pilot study.
AB  - PURPOSE: It is thought that Randall's plaques, calcium deposits in the renal
      papillae of patients with nephrolithiasis, may serve as a nidus for stone
      formation. We examined the density of renal papillae in patients with stones and
      control patients using attenuation measurements (HU) on Computed Tomography (CT)
      to determine whether nephrolithiasis is associated with radiographic changes in
      renal papillae. MATERIALS AND METHODS: Hounsfield density measurements of a 0.2
      cm2 area of the renal papillae of 17 patients with a single renal calyceal
      calculus and 15 age-matched control patients were performed. Measurements were
      done for renal papillae upper, middle, and lower pole calyces for all patients.
      Statistical comparisons were made using the student's t-test. RESULTS: Patients
      with nephrolithiasis and control patients were similar with respect to mean age
      (41.2 years versus 42.2 years, p=0.82) and baseline serum creatinine (0.86 mg/dl
      versus 0.93 mg/dl, p=0.21). Mean Hounsfield density of renal papillae of stone
      patients in calyces with stones was significantly greater than that of location
      matched papillae from control patients (54.4 versus 36.6, p<0.0001). Mean
      Hounsfield density of all papillae of the affected kidney (i.e., kidney with
      stone) in stone patients was significantly greater than that of control patients
      (50.9 versus 36.4, p<0.0001). Mean Hounsfield density of all papillae in the
      stone-free kidney of stone patients was significantly greater than that of
      control patients (50.0 versus 36.1, p<0.0001). In stone patients, when comparing
      the affected kidney with the stone-free kidney, there was no difference in mean
      papilla Hounsfield density (50.3 versus 50.9, p=0.59). CONCLUSIONS: Hounsfield
      density of the renal papilla is significantly increased in patients with
      nephrolithiasis when compared with age-matched controls. This is true of calyces
      with stones, calyces without stones in kidneys with stones, and calyces of the
      contralateral stone-free kidney. There is no difference in renal papilla
      Hounsfield density between kidneys with and without stones in patients with
      nephrolithiasis. In the future, this information may be useful in predicting
      which patients may develop nephrolithiasis.

PMID- 18831677
TI  - Connexin-caused genetic diseases and corresponding mouse models.
AB  - The human and mouse genomes contain 21 and 20 connexin genes, respectively.
      During the last 10-year period, genetic research on connexins has been stimulated
      by two parallel approaches: first, the characterization of genetic diseases that
      are caused by connexin mutations and, second, the generation and characterization
      of connexin knockout (null) mutated mice in which the coding region of nearly all
      connexin genes has been deleted. We summarize the current results of each of
      these two approaches. More recently, first results have been published in which
      connexin point mutations in human connexin genes were inserted at the
      corresponding position of the orthologous mouse gene. Under these conditions, the
      mutated connexin protein is expressed, in contrast to a connexin null mutation,
      and its interaction with other connexin isoforms or other connexin-binding
      proteins can be maintained. In this review, we discuss advantages and problems of
      such an approach and possible implications regarding the mechanism of the
      disease. The long-term goal is to understand the biologic function of each
      connexin isoform and the contribution of these proteins to the physiology of the
      corresponding organs in health and disease.

PMID- 18831678
TI  - Gap junctions in the control of vascular function.
AB  - Direct intercellular communication via gap junctions is critical in the control
      and coordination of vascular function. In the cardiovascular system, gap
      junctions are made up of one or more of four connexin proteins: Cx37, Cx40, Cx43,
      and Cx45. The expression of more than one gap-junction protein in the vasculature
      is not redundant. Rather, vascular connexins work in concert, first during the
      development of the cardiovascular system, and then in integrating smooth muscle
      and endothelial cell function, and in coordinating cell function along the length
      of the vessel wall. In addition, connexin-based channels have emerged as an
      important signaling pathway in the astrocyte-mediated neurovascular coupling.
      Direct electrical communication between endothelial cells and vascular smooth
      muscle cells via gap junctions is thought to play a relevant role in the control
      of vasomotor tone, providing the signaling pathway known as endothelium-derived
      hyperpolarizing factor (EDHF). Consistent with the importance of gap junctions in
      the regulation of vasomotor tone and arterial blood pressure, the expression of
      connexins is altered in diseases associated with vascular complications. In this
      review, we discuss the participation of connexin-based channels in the control of
      vascular function in physiologic and pathologic conditions, with a special
      emphasis on hypertension and diabetes.

PMID- 18831680
TI  - Polymorphonuclear neutrophil infiltration intensity as consequence of Entamoeba
      histolytica density in amebic colitis.
AB  - BACKGROUND: It has been suggested that the damage observed in invasive amebiasis
      is related to interactions between polymorphonuclear leukocytes (PMN) and
      Entamoeba histolytica trophozoites. We analyzed the relation between infiltrating
      inflammatory cell populations and E. histolytica density in intestinal amebic
      lesions. METHODS: Biopsies obtained endoscopically from patients with amebic
      colitis were analyzed to describe their morphologic abnormalities. Cellular
      populations and E. histolytica trophozoites were measured quantitatively in order
      to assess the correlation between infiltrating inflammatory cell populations and
      parasite density. RESULTS: Amebic lesions were most often located in the colon
      (55%). The histopathologic diagnoses were colitis in 31%, erosive colitis in 26%,
      and ulcerated colitis in 24%. The predominant cellular populations found in the
      lesions were lymphocytes (59.8%) (3,672 +/- 2,413/mm(2)) followed by PMN (17%)
      (1,038 +/- 1,171 PMN/mm(2)) (p < 0.01). A higher density of PMN infiltration was
      observed in severe cases. Cellular populations predictive of the presence of E.
      histolytica trophozoites (p = 0.047) were PMN (p = 0.019) and lymphocytes (p =
      0.033). The highest association was found between E. histolytica trophozoites and
      PMN (p = 0.0221). CONCLUSIONS: Neutrophils and lymphocytes, particularly the
      former, are associated significantly with the density of parasites. Our findings
      support the theory that PMN interaction with E. histolytica contributes to the
      pathogenesis of amebic intestinal lesions.

PMID- 18831681
TI  - In vitro susceptibilities of aerobic and facultatively anaerobic gram-negative
      bacilli isolated from patients with intra-abdominal infections worldwide: 2005
      results from Study for Monitoring Antimicrobial Resistance Trends (SMART).
AB  - BACKGROUND: The Study for Monitoring Antimicrobial Resistance Trends (SMART) is
      examining aerobic and facultatively anaerobic gram-negative bacilli (GNB)
      isolated from intra-abdominal infections. This report summarizes the 2005 annual
      data. METHODS: During 2005, 76 medical centers in 31 countries in five regions
      collected intra-abdominal GNB for antimicrobial susceptibility testing using
      broth microdilution according to the Clinical and Laboratory Standards Institute
      guidelines. RESULTS: A total of 5,476 unique aerobic and facultatively anaerobic
      GNB were isolated. Enterobacteriaceae accounted for 86% (4,711) of the total
      isolates. Among the 12 antimicrobial agents tested, the carbapenems and amikacin
      were the most reliably active against the Enterobacteriaceae, whereas
      ampicillin/sulbactam most often was the least active. Escherichia coli was the
      species most commonly isolated, at 48% (2,654). Extended-spectrum beta-lactamases
      (ESBLs) were detected phenotypically in 12% (325/2,329) of E. coli and 18%
      (151/856) of Klebsiella spp. In general, ESBL producers demonstrated lower
      susceptibility to the majority of the antibiotics than the non-producers;
      however, ESBL producers usually were susceptible to the carbapenems tested.
      CONCLUSIONS: In 2005, antibiotic resistance continued to be a problem among GNB
      isolated from intra-abdominal infections, with the highest resistance rates
      observed in the Asia/Pacific region. Imipenem-cilastatin, ertapenem, and amikacin
      were the agents most consistently active in vitro against the Enterobacteriaceae
      isolated.

PMID- 18831679
TI  - Oxidative stress, lens gap junctions, and cataracts.
AB  - The eye lens is constantly subjected to oxidative stress from radiation and other
      sources. The lens has several mechanisms to protect its components from oxidative
      stress and to maintain its redox state, including enzymatic pathways and high
      concentrations of ascorbate and reduced glutathione. With aging, accumulation of
      oxidized lens components and decreased efficiency of repair mechanisms can
      contribute to the development of lens opacities or cataracts. Maintenance of
      transparency and homeostasis of the avascular lens depend on an extensive network
      of gap junctions. Communication through gap junction channels allows
      intercellular passage of molecules (up to 1 kDa) including antioxidants. Lens gap
      junctions and their constituent proteins, connexins (Cx43, Cx46, and Cx50), are
      also subject to the effects of oxidative stress. These observations suggest that
      oxidative stress-induced damage to connexins (and consequent altered
      intercellular communication) may contribute to cataract formation.

PMID- 18831682
TI  - Surgical site infection in children: prospective analysis of the burden and risk
      factors in a sub-Saharan African setting.
AB  - BACKGROUND: Surgical site infections (SSI) add substantially to the morbidity of
      surgical patients. Our hypothesis was that the SSI rate is high in our setting,
      but there were no data regarding the prevalence and risk factors. METHODS: Three
      hundred twenty-two children who had surgery (elective 144, emergency 178) between
      January, 2001 and September, 2005 were studied prospectively. All patients with
      clean-contaminated, contaminated, and dirty incisions received prophylactic
      antibiotics. Data were collected using a tool that captured demographics,
      diagnosis, co-morbid conditions, type of surgical incision, nature of surgery,
      type of anesthesia, use of perioperative antibiotics, and duration of surgery.
      Information also was collected postoperatively on the development of SSI, type of
      infection, associated signs, the day the infection was identified, the findings
      in cultures of swabs from infected incisions, duration of hospital stay, and
      outcome. The chi-square test for categorical variables was used to test for
      significance of association. The p value for significance was set at 0.05.
      RESULTS: Seventy-six patients (23.6%) consisting of 40 boys and 36 girls
      developed SSI. The median age was nine months (range, 2 days-12 years) for those
      who developed SSI and 15 months (range, 1 day-13 years) for those who did not.
      The SSI rate was 14.3% in clean incisions, 19.3% in clean-contaminated incisions,
      27.3% in contaminated incisions, and 60% in dirty incisions (p < 0.05). The
      infection rate was 25.8% in emergency procedures and 20.8% in elective procedures
      (p > 0.05). The infection rate was 31% in operations lasting >or= 2 h and 17.3%
      in operations lasting < 2 h (p < 0.05). Infection was detected before the eighth
      postoperative day in 56 of the patients (74.6%) with SSI, and bacteria were
      cultured from the incision in 32 patients (42.7%). The average length of stay was
      26.1 days (range, 8-127 days) in patients with SSI and 18.0 days (range, 1-99
      days) in those without SSI (p < 0.05). The mortality rate of patients with SSI
      was 10.5%, with six of the eight deaths related directly to the SSI, compared
      with a mortality rate of 4.1% in patients without SSI (p < 0.05). CONCLUSION: The
      burden of SSI in this setting is high. The degree of incisional contamination and
      a long duration of surgery (>or= 2 h) are important risk factors.

PMID- 18831683
TI  - The contribution of epithelial sodium channels to alveolar function in health and
      disease.
AB  - Amiloride-sensitive epithelial sodium channels (ENaC) play an important role in
      lung sodium transport. Sodium transport is closely regulated to maintain an
      appropriate fluid layer on the alveolar surface. Both alveolar type I and II
      cells have several different sodium-permeable channels in their apical membranes
      that play a role in normal lung physiology and pathophysiology. In many
      epithelial tissues, ENaC is formed from three subunit proteins: alpha, beta, and
      gamma ENaC. Part of the diversity of sodium-permeable channels in lung arises
      from assembling different combinations of these subunits to form channels with
      different biophysical properties and different mechanisms for regulation. Thus,
      lung epithelium has enormous flexibility to alter the magnitude of salt and water
      transport. In lung, ENaC is regulated by many transmitter and hormonal agents.
      Regulation depends upon the type of sodium channel but involves controlling the
      number of apical channels and/or the activity of individual channels.

PMID- 18831684
TI  - Comparative social cognition.
AB  - Theory of mind is said to be uniquely human. Is this statement justified? Thirty
      years of research on a variety of species has produced differences in opinion,
      from unequivocal positive evidence to no evidence at all for mental attribution
      in animals. Our review concludes that animals are excellent ethologists, but on
      the whole, poor psychologists. Those studies that we believe present a good case
      for mental attribution all possess high ecological validity, including studies on
      food competition by chimpanzees and cache-protection strategies by corvids. Even
      though the current focus of research on prediction rather than explanation may be
      misplaced, we believe the field is now in a strong position to discover what
      animals really know about their fellow beings, be it based on simple
      associations, behavior reading, mind reading, or something else.

PMID- 18831685
TI  - Effects of temporal hydrostatic pressure on tissue-engineered bovine articular
      cartilage constructs.
AB  - The objective of this study was to determine the effects of temporal hydrostatic
      pressure (HP) on the properties of scaffoldless bovine articular cartilage
      constructs. The study was organized in three phases: First, a suitable control
      for HP application was identified. Second, 10 MPa static HP was applied at three
      different timepoints (6-10 days, 10-14 days, and 14-18 days) to identify a window
      in construct development when HP application would be most beneficial. Third, the
      temporal effects of 10-14-day static HP application, as determined in phase II,
      were assessed at 2, 4, and 8 weeks. Compressive and tensile mechanical
      properties, GAG and collagen content, histology for GAG and collagen, and
      immunohistochemistry for collagen types I and II were assessed. When a culture
      control identified in phase I was used in phase II, HP application from 10 to 14
      days resulted in a significant 1.4-fold increase in aggregate modulus,
      accompanied by an increase in GAG content, while HP application at all timepoints
      enhanced tensile properties and collagen content. In phase III, HP had an
      immediate effect on GAG content, collagen content, and compressive stiffness,
      while there was a delayed increase in tensile stiffness. The enhanced tensile
      stiffness was still present at 8 weeks. For the first time, this study examined
      the immediate and long-term effects of HP on biomechanical properties, and
      demonstrated that HP has an optimal application time in construct development.
      These findings are exciting as HP stimulation allowed for the formation of robust
      tissue-engineered cartilage; for example, 10 MPa static HP resulted in an
      aggregate modulus of 273 +/- 123 kPa, a Young's modulus of 1.6 +/- 0.4 MPa, a
      GAG/wet weight of 6.1 +/- 1.4%, and a collagen/wet weight of 10.6 +/- 2.4% at 4
      weeks.

PMID- 18831686
TI  - A comparative study of shear stresses in collagen-glycosaminoglycan and calcium
      phosphate scaffolds in bone tissue-engineering bioreactors.
AB  - The increasing demand for bone grafts, combined with their limited availability
      and potential risks, has led to much new research in bone tissue engineering.
      Current strategies of bone tissue engineering commonly use cell-seeded scaffolds
      and flow perfusion bioreactors to stimulate the cells to produce bone tissue
      suitable for implantation into the patient's body. The aim of this study was to
      quantify and compare the wall shear stresses in two bone tissue engineering
      scaffold types (collagen-glycosaminoglycan (CG) and calcium phosphate) exposed to
      fluid flow in a perfusion bioreactor. Based on micro-computed tomography images,
      three-dimensional numerical computational fluid dynamics (CFD) models of the two
      scaffold types were developed to calculate the wall shear stresses within the
      scaffolds. For a given flow rate (normalized according to the cross-sectional
      area of the scaffolds), shear stress was 2.8 times as high in the CG as in the
      calcium-phosphate scaffold. This is due to the differences in scaffold geometry,
      particularly the pore size (CG pore size approximately 96 microm, calcium
      phosphate pore size approximately 350 microm). The numerically obtained results
      were compared with those from an analytical method that researchers use widely
      experimentalists to determine perfusion flow rates in bioreactors. Our CFD
      simulations revealed that the cells in both scaffold types were exposed to a wide
      range of wall shear stresses throughout the scaffolds and that the analytical
      method predicted shear stresses 12% to 21% greater than those predicted using the
      CFD method. This study demonstrated that the wall shear stresses in calcium
      phosphate scaffolds (745.2 mPa) are approximately 40 times as high as in CG
      scaffolds (19.4 mPa) when flow rates are applied that have been experimentally
      used to stimulate the release of prostaglandin E(2). These findings indicate the
      importance of using accurate computational models to estimate shear stress and
      determine experimental conditions in perfusion bioreactors for tissue
      engineering.

PMID- 18831687
TI  - Improving linear stiffness of the cell-seeded collagen sponge constructs by
      varying the components of the mechanical stimulus.
AB  - In vitro mechanical stimulation has been reported to induce cell alignment and
      increase cellular proliferation and collagen synthesis. Our group has previously
      reported that in vitro mechanical stimulation of tissue-engineered tendon
      constructs significantly increases construct stiffness and repair biomechanics
      after surgery. However, these studies used a single mechanical stimulation
      profile, the latter composed of multiple components whose individual and combined
      effects on construct properties remain unknown. Thus, the purpose of this study
      was to understand the relative importance of a subset of these components on
      construct stiffness. To try to optimize the resulting mechanical stimulus, we
      used an iterative process to vary peak strain, cycle number, and cycle repetition
      while controlling cycle frequency (1 Hz), rise and fall times (25% and 17% of the
      period, respectively), hours of stimulation/day (8 h/day), and total time of
      stimulation (12 days). Two levels of peak strain (1.2 % and 2.4%), cycle number
      (100 and 3000 cycles/day), and cycle repetition (1 and 20) were first examined.
      Higher levels of peak strain and cycle number were then examined to optimize the
      stimulus using response surface methodology. Our results indicate that constructs
      stimulated with 2.4% strain, 3000 cycles/day, and one cycle repetition produced
      the stiffest constructs. Given the significant positive correlations we have
      previously found between construct stiffness and repair biomechanics at 12 weeks
      post-surgery, these in vitro enhancements offer the prospect of further improving
      repair biomechanics.

PMID- 18831688
TI  - Dynamic straining combined with fibrin gel cell seeding improves strength of
      tissue-engineered small-diameter vascular grafts.
AB  - Vascular tissue engineering represents a promising approach for the development
      of living small-diameter vascular grafts that can be used for replacement
      therapy. The culture of strong human tissue-engineered (TE) vascular grafts has
      required long culture times, up to several months, whether or not combined with
      gene therapy. This article describes the culture of strong, genetically
      unmodified, human TE vascular grafts in 4 weeks Small-diameter vascular grafts
      were engineered using a fast-degrading polyglycolic acid scaffold coated with
      poly-4-hydroxybutyrate combined with fibrin gel and seeded with myofibroblasts
      isolated from discarded saphenous veins from patients undergoing coronary bypass
      surgery. The TE grafts were subjected to dynamic strain conditions. After 28 d of
      in vitro culture, the grafts demonstrated burst pressures of 903 +/- 123 mmHg.
      Comparison with native vessels (intact human left internal mammary arteries
      (LIMAs) and saphenous veins) showed no significant differences in the amount of
      DNA, whereas the TE vessels contained approximately 50% of the native collagen
      content. In the physiological pressure range, up to 300 mmHg, the mechanical
      properties of the TE vessels were comparable to the LIMA. In this study, we
      showed that dynamic conditioning combined with fibrin gel cell seeding enhances
      the mechanical properties of small-diameter TE grafts. These grafts might provide
      a promising alternative to currently used vascular replacements.

PMID- 18831689
TI  - Climate change and temperature-dependent sex determination: can individual
      plasticity in nesting phenology prevent extreme sex ratios?
AB  - Under temperature-dependent sex determination (TSD), temperatures experienced by
      embryos during development determine the sex of the offspring. Consequently,
      populations of organisms with TSD have the potential to be strongly impacted by
      climatic warming that could bias offspring sex ratio, a fundamental demographic
      parameter involved in population dynamics. Moreover, many taxa with TSD are
      imperiled, so research on this phenomenon, particularly long-term field study,
      has assumed great urgency. Recently, turtles with TSD have joined the diverse
      list of taxa that have demonstrated population-level changes in breeding
      phenology in response to recent climate change. This raises the possibility that
      any adverse impacts of climate change on populations may be alleviated by
      individual plasticity in nesting phenology. Here, we examine data from a long
      term study on a population of painted turtles (Chrysemys picta) to determine
      whether changes in phenology are due to individual plasticity and whether
      individual plasticity in the timing of nesting has the capacity to offset the sex
      ratio effects of a rise in climatic temperature. We find that individual females
      show plasticity in the date of first nesting each year, and that this plasticity
      depends on the climate from the previous winter. First nesting date is not
      repeatable within individuals, suggesting that it would not respond to selection.
      Sex ratios of hatchlings within a nest declined nonsignificantly over the nesting
      season. However, small increases in summer temperature had a much stronger effect
      on nest sex ratios than did laying nests earlier in the season. For this and
      other reasons, it seems unlikely that individual plasticity in the timing of
      nesting will offset the effects of climate change on sex ratios in this
      population, and we hypothesize that this conclusion applies to other populations
      with TSD.

PMID- 18831690
TI  - CD4+ T helper cell responses against human bocavirus viral protein 2 viruslike
      particles in healthy adults.
AB  - BACKGROUND: Human bocavirus (HBoV) was recently described as a new member of the
      Parvoviridae family, and its possible association with respiratory illness in
      infants has been discussed. To date, HBoV genomes have been detected worldwide in
      respiratory tract samples obtained from children with pulmonary diseases, whereas
      only limited data on virus-specific immunity are available, mainly because of the
      lack of recombinant viral antigens. METHODS: HBoV viruslike particles (VLPs) were
      produced in insect cells and characterized by electron microscopy and cesium
      chloride gradient centrifugation. HBoV viral protein 2 (VP2)-specific antibodies
      and CD4+ T helper cell responses were analyzed by enzyme-linked immunosorbent
      assay and enzyme-linked immunospot assay. RESULTS: VP2 capsid proteins of HBoV
      were produced in insect cells infected with a recombinant baculovirus, and the
      formation of icosahedral VLPs (diameter, 21-25 nm; sedimentation density, 1.33
      g/cm(3)) was demonstrated. A significant increase in secretion of VP2-specific
      interferon-gamma was detected in cultures of peripheral blood mononuclear cells
      obtained from 69 healthy adults found to be positive for HBoV-specific
      immunoglobulin G antibodies, compared with control stimulations. In parallel, T
      cell responses against identically expressed parvovirus B19 VP2 VLPs were
      frequently observed in the individuals studied, without there being obvious cross
      reactions between HBoV and parvovirus B19. CONCLUSIONS: Data suggest the presence
      of HBoV-specific immune responses in adults and strongly support a high
      prevalence of HBoV among humans.

PMID- 18831691
TI  - Plasma folate level and high-dose folate supplementation predict sulfadoxine
      pyrimethamine treatment failure in pregnant women in Western kenya who have
      uncomplicated malaria.
AB  - Sulfadoxine-pyrimethamine (SP) inhibits folate metabolism by the malaria
      parasite. We investigated the association between folate levels and SP failure in
      pregnant women. Data from a trial to assess the effect that folate
      supplementation has on SP failure in 467 pregnant women were analyzed. Plasma
      folate levels were determined at enrollment and at day 7. High baseline folate
      levels, high parasite densities, and age <20 years were risk factors for SP
      failure. High-dose (5 mg daily) folate supplementation or high folate levels at
      day 7 were independent risk factors. Therefore, pregnant women receiving SP
      should receive low-/moderate-dose folate supplementation. TRIAL REGISTRATION:
      http://www.clinicaltrials.gov identifier: NCT00130065.

PMID- 18831695
TI  - Association of a single-nucleotide polymorphism in the pregnane X receptor (PXR
      63396C-->T) with reduced concentrations of unboosted atazanavir.
AB  - This study investigated pregnane X receptor polymorphisms in relation to
      unboosted atazanavir plasma concentrations in 2 cohorts of patients. The
      polymorphism 63396T-->C predicted concentrations below the minimum effective
      concentration (150 ng/mL) with odds ratios of 18 (P = .008) and 5.13 (P = .02).
      Prospective studies determining potential clinical usefulness are now warranted.

PMID- 18831696
TI  - Drug toxicity, HIV progression, or comorbidity of aging: does tipranavir use
      increase the risk of intracranial hemorrhage?
AB  - The US Food and Drug Administration has issued a warning that tipranavir may be
      associated with increased risk of intracranial hemorrhage. We studied 2 large
      cohorts to estimate the background rate of intracranial hemorrhage and compared
      it with rates reported among persons who had been exposed to tipranavir.

PMID- 18831697
TI  - An HIV-positive man with cough, fever, and progressive dyspnea. Disseminated
      cytomegalovirus (CMV) infection.

PMID- 18831698
TI  - Nucleoside reverse-transcriptase inhibitor use, cirrhosis, and end-stage liver
      disease in HIV-infected patients.

PMID- 18831700
TI  - Smartphone utilities for infectious diseases specialists.

PMID- 18831701
TI  - Relationship between shingles (varicella zoster) and hypercalcemia not found.

PMID- 18831703
TI  - Active surveillance cultures for methicillin-resistant Staphylococcus aureus in
      an intensive care unit.

PMID- 18831704
TI  - The role of air travel in the spread of mumps.

PMID- 18831705
TI  - Methicillin-resistant Staphylococcus aureus: misinterpretation and
      misrepresentation of active detection and isolation.

PMID- 18831711
TI  - Effects of pravastatin on functional capacity in patients with chronic
      obstructive pulmonary disease and pulmonary hypertension.
AB  - PH (pulmonary hypertension) often complicates the disease course of patients with
      COPD (chronic obstructive pulmonary disease) and is an indication of a worse
      prognosis. In the present study, we assessed whether pravastatin administration
      was effective in improving PH and exercise capacity in COPD patients with PH, and
      whether the pulmonary protection was mediated by inhibiting ET-1 (endothelin-1)
      production. In a double-blind parallel design, 53 COPD patients with PH were
      randomly assigned to receive either placebo or pravastatin (40 mg/day) over a
      period of 6 months at a medical centre. Baseline characteristics were similar in
      both groups. The exercise time remained stable throughout the study in the
      placebo group. After 6 months, the exercise time significantly increased 52% from
      660+/-352 to 1006+/-316 s (P<0.0001) in pravastatin-treated patients. With
      pravastatin, echocardiographically derived systolic PAP (pulmonary artery
      pressure) decreased significantly from 47+/-8 to 40+/-6 mmHg. There was
      significant improvement in the Borg dyspnoea score after administering
      pravastatin. Despite unchanged plasma ET-1 levels throughout the study, urinary
      excretion of the peptide was decreased and significantly correlated with an
      improvement in exercise time in pravastatin-treated patients (r=-0.47, P=0.01).
      In conclusion, pravastatin significantly improved exercise tolerance, and
      decreased PH and dyspnoea during exercise in COPD patients with PH, probably by
      inhibiting ET-1 synthesis.

PMID- 18831712
TI  - BCL11B enhances TCR/CD28-triggered NF-kappaB activation through up-regulation of
      Cot kinase gene expression in T-lymphocytes.
AB  - BCL11B is a transcriptional regulator with an important role in T-cell
      development and leukaemogenesis. We demonstrated recently that BCL11B controls
      expression from the IL (interleukin)-2 promoter through direct binding to the US1
      (upstream site 1). In the present study, we provide evidence that BCL11B also
      participates in the activation of IL-2 gene expression by enhancing NF-kappaB
      (nuclear factor kappaB) activity in the context of TCR (T-cell receptor)/CD28
      triggered T-cell activation. Enhanced NF-kappaB activation is not a consequence
      of BCL11B binding to the NF-kappaB response elements or association with the NF
      kappaB-DNA complexes, but rather the result of higher translocation of NF-kappaB
      to the nucleus caused by enhanced degradation of IkappaB (inhibitor of NF
      kappaB). The enhanced IkappaB degradation in cells with increased levels of
      BCL11B was specific for T-cells activated through the TCR, but not for cells
      activated through TNFalpha (tumour necrosis factor alpha) or UV light, and was
      caused by increased activity of IkappaB kinase, as indicated by its increase in
      phosphorylation. As BCL11B is a transcription factor, we investigated whether the
      expression of genes upstream of IkappaB kinase in the TCR/CD28 signalling pathway
      was affected by increased BCL11B expression, and found that Cot (cancer Osaka
      thyroid oncogene) kinase mRNA levels were elevated. Cot kinase is known to
      promote enhanced IkappaB kinase activity, which results in the phosphorylation
      and degradation of IkappaB and activation of NF-kappaB. The implied involvement
      of Cot kinase in BCL11B-mediated NF-kappaB activation in response to TCR
      activation is supported by the fact that a Cot kinase dominant-negative mutant or
      Cot kinase siRNA (small interfering RNA) knockdown blocked BCL11B-mediated NF
      kappaB activation. In support of our observations, in the present study we report
      that BCL11B enhances the expression of several other NF-kappaB target genes, in
      addition to IL-2. In addition, we provide evidence that BCL11B associates with
      intron 2 of the Cot kinase gene to regulate its expression.

PMID- 18831713
TI  - Isolation at physiological temperature of detergent-resistant membranes with
      properties expected of lipid rafts: the influence of buffer composition.
AB  - The failure of most non-ionic detergents to release patches of DRM (detergent
      resistant membrane) at 37 degrees C undermines the claim that DRMs consist of
      lipid nanodomains that exist in an L(o) (liquid ordered) phase on the living cell
      surface. In the present study, we have shown that inclusion of cations (Mg(2+),
      K(+)) to mimic the intracellular environment stabilizes membranes during
      solubilization sufficiently to allow the isolation of DRMs at 37 degrees C, using
      either Triton X-100 or Brij 96. These DRMs are sensitive to chelation of
      cholesterol, maintain outside-out orientation of membrane glycoproteins, have
      prolonged (18 h) stability at 37 degrees C, and are vesicles or sheets up to 150
      200 nm diameter. DRMs containing GPI (glycosylphosphatidylinositol)-anchored
      proteins PrP (prion protein) and Thy-1 can be separated by immunoaffinity
      isolation, in keeping with their separate organization and trafficking on the
      neuronal surface. Thy-1, but not PrP, DRMs are associated with actin. EM
      (electron microscopy) immunohistochemistry shows most PrP, and some Thy-1, to be
      clustered on DRMs, again maintaining their organization on the neuronal surface.
      For DRMs labelled for either protein, the bulk of the surface of the DRM is not
      labelled, indicating that the GPI-anchored protein is a minor component of its
      lipid domain. These 37 degrees C DRMs thus have properties expected of raft
      membrane, yet pose more questions about how proteins are organized within these
      nanodomains.

PMID- 18831714
TI  - Phosphorylated and non-phosphorylated forms of catechol O-methyltransferase in
      rat liver, brain and other tissues.
AB  - Seven different forms of the enzyme COMT (catechol O-methyltransferase) were
      found in isolated rat hepatocytes by two-dimensional gel electrophoresis and
      immunoblotting: five small variants (S-COMT) and two large variants (L-COMT). The
      identities of these COMT forms were verified by tryptic fingerprinting using
      MALDI-TOF (matrix-assisted laser-desorption ionization-time-of-flight) MS, and by
      amino acid sequencing using ESI-IT-MS/MS (electrospray ionization with ion-trap
      tandem MS). Analysis of tissue distributions showed that the S-COMT forms were
      highly expressed in liver and kidney, whereas L-COMT was expressed more strongly
      in other tissues. Both of the L-COMT forms were found in all of the tissues
      examined except the heart, which expressed only the most acidic form, and the
      kidney, which expressed only the most basic form. Subcellular fractionation
      revealed the presence of both S-COMT and L-COMT in soluble, as well as
      sedimentable, fractions, suggesting that they should be classified by size rather
      than (as previously) by localization. Several of the S-COMT forms were N
      acetylated, and the two most acidic forms were found to be phosphorylated at
      Ser(260). One of the latter was unique to liver cells; the other was also found
      in kidney, brain and thymus. Among the non-phosphorylated S-COMT forms, one was
      ubiquitous, one was found in testis and liver, and a third was found in liver,
      kidney and thymus. No other phosphorylated sites were found, suggesting that the
      pI differences distinguishing between the various COMT forms are due to some as
      yet unidentified structural modification(s).

PMID- 18831717
TI  - Latest developments in the treatment of lung cancer.

PMID- 18831718
TI  - Overview of advanced non-small-cell lung cancer treatment in Mexico.
AB  - BACKGROUND: Lung cancer is the leading cause of cancer-related deaths among males
      and the second among females. The importance of lung cancer is a major public
      health problem and there is a need to find effective therapies for its
      management. Erlotinib has been approved to treat non-small-cell lung cancer. The
      author's experience in the use of erlonitib in lung cancer patients in Mexico
      City is described below. METHODS: The series includes 17 consecutive patients
      treated for advanced lung cancer. All patients had measurable disease. Treatment
      continues until disease progression or significant toxicity occurs. Among
      patients, adenocarcinoma was the most common tumor histology, followed by
      bronchioloalveolar tumor, and epidermoid carcinoma. Nine patients received
      erlotinib as first-line therapy. Of the remaining 8 patients, 4 had undergone
      surgery, 2 had received chemotherapy, and 2 had received combined chemotherapy
      and radiotherapy. RESULTS: Four patients achieved complete remission of the
      disease, and 7 showed partial response. Five subjects experienced disease
      progression, and one patient showed stable disease. The most significant cases
      were two non-smokers women with bronchioloalveolar cancer, who remain in complete
      remission after erlotinib treatment. A non-smoker male patient with
      adenocarcinoma histology, who rejected chemotherapy and radiotherapy, it remains
      in complete remission after 15 months of treatment. A man with epidermoid
      carcinoma, with previous surgery and treated with chemotherapy and radiotherapy,
      with tumor recurrence, showed a complete 15-month remission with erlotinib. It
      was observed clinical response due to treatment with erlotinib despite the tumor
      histopathology, but therapeutic response was better in patients without smoking
      history. The most common adverse events associated with erlotinib therapy were
      dermatologic. After discontinuing treatment for a short period, patients were
      again given erlotinib without experiencing toxic effects. Hepatotoxic side
      effects associated to erlotinib were mild and reversible. CONCLUSION: Data from
      this small series of patients support findings reported in the literature. Female
      non-smokers showed the best therapeutic response to erlotinib treatment.
      Erlotinib could be considered as a first-line therapeutic option in elderly
      patients with locally advanced or metastatic lung cancer, or in women with
      adenocarcinoma.

PMID- 18831719
TI  - First- and second-line treatment of advanced metastatic non-small-cell lung
      cancer: a global view.
AB  - Treatment of non-small-cell lung cancer is dependent on disease stage. For
      patients with metastasis or locally advanced disease, the importance of finding
      therapeutic schemes that may benefit this population is important. This review
      discusses therapeutic options for first- and second-line treatment in patients
      with advanced non-small-cell lung cancer. According to current data, the
      combination of two cytotoxic agents is the optimum first-line treatment for
      patients with non-small-cell lung cancer and performance status of 0-1. Addition
      of bevacizumab has shown to provide an even longer survival and to increase
      response rate. Within the first-line setting, erlotinib appears to be effective
      in the treatment of elderly patients who would not derive a benefit from standard
      chemotherapy or those refusing standard chemotherapy. The administration of
      erlotinib as first-line maintenance therapy is being assessed. There are
      currently three drugs approved for second-line treatment of patients with
      advanced non-small-cell lung cancer after failure of first-line chemotherapy.
      These drugs have proven to be effective in phase III trials. In the phase III
      trial BR.21 study, the response rate was 8.9% in the erlonitib group, and less
      than 1% in placebo; median response duration was 7.9 months and 3.7 months,
      respectively; and the median survival was 6.7 months and 4.7 with erlotinib and
      placebo, respectively. One-year survival was 31% and 21% with erlotinib and
      placebo, respectively. In addition, the BR.21 trial revealed that significantly
      greater improvements in overall quality of life and in both physical and
      emotional functioning were observed in the erlotinib arm as compared with the
      placebo arm. Erlotinib is not significantly associated with hematologic adverse
      effects. Erlotinib is administered orally, and does not require concomitant
      administration of other drugs, thus causing patients less inconvenience. Analysis
      of data from different subgroups included in the BR.21 trial show that overall
      survival is similar among women and men, among patients with adenocarcinoma and
      epidermoid carcinoma or Asian patients compared with other ethnicities.
      Combination of erlotinib and bevacizumab in the second-line treatment of patients
      with advanced disease has been evaluated as anti-angiogenic properties. This
      combination therapy has provided promising results which should be confirmed in
      future studies.

PMID- 18831720
TI  - Conclusions of the expert panel: importance of erlotinib as a second-line
      therapeutic option.
AB  - During the Experts Meeting on Lung Cancer, participants emphasized the usefulness
      of erlotinib as second-line therapy for lung cancer. They noted that, although
      there are no comparative studies, erlotinib could be as effective as docetaxel
      and pemetrexed in second-line therapy. Regarding the toxicity profile of each of
      these drugs - one of the key issues considered in the meeting - specialists
      pointed out how important it is to clearly identify existing differences in this
      issue. Each drug has different degrees of toxicity, and this information is
      crucial at the time of choosing the therapeutic regimen. Erlotinib treatment
      could be an effective option for second-line therapy.

PMID- 18831721
TI  - Using MRI of the optic nerve sheath to detect elevated intracranial pressure.
AB  - The current gold standard for the diagnosis of elevated intracranial pressure
      (ICP) remains invasive monitoring. Given that invasive monitoring is not always
      available or clinically feasible, there is growing interest in non-invasive
      methods of assessing ICP using diagnostic modalities such as ultrasound or
      magnetic resonance imaging (MRI). Increased ICP is transmitted through the
      cerebrospinal fluid surrounding the optic nerve, causing distention of the optic
      nerve sheath diameter (ONSD). In this issue of Critical Care, Geeraerts and
      colleagues describe a non-invasive method of diagnosing elevated ICP using MRI to
      measure the ONSD. They report a positive correlation between measurements of the
      ONSD on MRI and invasive ICP measurements. If the findings of this study can be
      replicated in larger populations, this technique may be a useful non-invasive
      screening test for elevated ICP in select populations.

PMID- 18831722
TI  - When bubbles burst.

PMID- 18831723
TI  - Observing bacteria through the lens of social evolution.
AB  - Explaining the evolution of cooperative behavior is a long-standing problem for
      which much theory has been developed. A recent paper in BMC Biology tests central
      elements of this theory by manipulating a simple bacterial experimental system.
      This approach is useful for assessing the principles of social evolution, but we
      argue that more effort must be invested in the inverse problem: using social
      evolution theory to understand the lives of bacteria.

PMID- 18831724
TI  - Archaea at St Andrews.
AB  - A report of the Biochemical Society meeting 'The Molecular Biology of Archaea',
      St Andrews, UK, 19-21 August 2008.

PMID- 18831725
TI  - Luminal B breast tumors are not HER2 positive.

PMID- 18831727
TI  - The evolving role of oestrogen receptor beta in clinical breast cancer.
AB  - Controversy surrounds the potential clinical importance of oestrogen receptor
      (ER)beta in breast cancer, and three recent papers have sought to resolve this.
      In the present issue of Breast Cancer Research Novelli and colleagues explored
      the significance of ERbeta1 expression in 936 breast cancer patients, and they
      showed diverse relationships according to lymph node status. A second paper
      examined 442 breast cancers in which ERbeta1 was an independent predictor of
      recurrence, disease-free survival and overall survival. Finally a third paper
      showed that ERbeta2 was a powerful prognostic indicator in 757 breast cancers but
      this was dependent on cellular location, with nuclear ERbeta2 expression
      predicting good survival whilst cytoplasmic expression predicted worse outcome.
      These papers point to a clinical role for ERbeta in breast cancer and shall be
      discussed.

PMID- 18831728
TI  - SCLC extensive disease--treatment guidance by extent or/and biology of response?
AB  - In extensive disease of small cell lung cancer a doubling of the one-year
      survival rate was reported in August 2007 by prophylactic cranial irradiation
      applied to patients who experienced any response to initial chemotherapy. We
      discuss the treatment concept of extensive disease in the face of the latest
      results and older studies with additional thoracic irradiation in this subgroup.
      A randomized trial with prophylactic cranial irradiation published in 1999
      demonstrated an improvement of 5-year-overall-survival for complete responders
      (at least at distant levels) receiving additional thoracic radiochemotherapy
      compared to chemotherapy alone (9.1% vs. 3.7%). But, these results were almost
      neglected and thoracic radiotherapy was not further investigated for good
      responders of extensive disease. However, in the light of current advances by
      prophylactic cranial irradiation these findings are noteworthy on all accounts.
      Considering both, a possible interpretation of these data could be a survival
      benefit of local control by simultaneous thoracic radiochemotherapy in the case
      of improved distant control due to chemotherapy and prophylactic cranial
      irradiation. Furthermore the question arises whether the tumor biology indicated
      by the response to chemotherapy should be integrated in the present
      classification.

PMID- 18831729
TI  - Prune belly syndrome in an Egyptian infant with Down syndrome: a case report.
AB  - INTRODUCTION: Prune belly syndrome is a rare congenital anomaly of uncertain
      aetiology almost exclusive to males. The association between prune belly syndrome
      and Down syndrome is very rare. CASE PRESENTATION: A 4-month-old Egyptian boy was
      admitted to our institute for management of acute bronchiolitis. He was born at
      full term by normal vaginal delivery. His mother, a 42-year-Egyptian villager
      with six other children, had no antenatal or prenatal care. On examination, the
      boy was found to be hypotonic. In addition to features of Down syndrome,
      karyotyping confirmed the diagnosis of trisomy 21. Ultrasound examination of the
      abdomen showed bilateral gross hydronephrosis with megaureter. Micturating
      cystourethrography showed grade V vesicoureteric reflux bilaterally with no
      urethral obstruction. Serum creatinine concentration was 90 mumol/litre, serum
      sodium was 132 mmol/litre and serum potassium was 5.9 mmol/litre. CONCLUSION: We
      report an Egyptian infant with Down syndrome and prune belly syndrome. The
      incidence of this association is unknown. Routine antenatal ultrasonography will
      help in discovering renal anomalies which can be followed postnatally. Postnatal
      detection of prune belly syndrome necessitates full radiological investigation to
      detect any renal anomalies. Early diagnosis of this syndrome and determining its
      optimal treatment are very important in helping to avoid its fatal course.

PMID- 18831730
TI  - Bezoar in gastro-jejunostomy presenting with symptoms of gastric outlet
      obstruction: a case report and review of the literature.
AB  - INTRODUCTION: Gastric outlet obstruction usually presents with non-bilious
      vomiting, colicky epigastric pain, loss of appetite and occasionally, upper
      gastrointestinal bleeding. Causes can be classified as benign or malignant, or as
      extra- or intraluminal. Gastrojejunostomy is a well-recognised surgical procedure
      performed to bypass gastric outlet obstruction. A bezoar occurs most commonly in
      patients with impaired gastrointestinal motility or with a history of gastric
      surgery. It is an intestinal concretion, which fails to pass along the alimentary
      canal. CASE PRESENTATION: A 62-year-old Asian woman with a history of
      gastrojejunostomy for peptic ulcer disease was admitted to hospital with
      epigastric pain, vomiting and dehydration. All investigations concluded gastric
      outlet obstruction secondary to a "stricture" at the site of gastrojejunostomy.
      Subsequent laparotomy revealed that the cause of the obstruction was a bezoar.
      CONCLUSION: Many bezoars can be removed endoscopically, but some will require
      operative intervention. Once removed, emphasis must be placed upon prevention of
      recurrence. Surgeons must learn to recognise and classify bezoars in order to
      provide the most effective therapy.

PMID- 18831731
TI  - French database of children and adolescents with Prader-Willi syndrome.
AB  - BACKGROUND: Prader-Willi syndrome (PWS) is a rare multisystem genetic disease
      leading to severe complications mainly related to obesity. We strongly lack
      information on the natural history of this complex disease and on what factors
      are involved in its evolution and its outcome. One of the objectives of the
      French reference centre for Prader-Willi syndrome set-up in 2004 was to set-up a
      database in order to make the inventory of Prader-Willi syndrome cases and
      initiate a national cohort study in the area covered by the centre. DESCRIPTION:
      the database includes medical data of children and adolescents with Prader-Willi
      syndrome, details about their management, socio-demographic data on their
      families, psychological data and quality of life of the parents. The tools and
      organisation used to ensure data collection and data quality in respect of good
      clinical practice procedures are discussed, and main characteristics of our
      Prader-Willi population at inclusion are presented. CONCLUSION: this database
      covering all the aspects of PWS clinical, psychological and social profiles,
      including familial psychological and quality of life will be a powerful tool for
      retrospective studies concerning this complex and multi factorial disease and
      could be a basis for the design of future prospective multicentric studies. The
      complete database and the Stata.do files are available to any researcher wishing
      to use them for non-commercial purposes and can be provided upon request to the
      corresponding author.

PMID- 18831732
TI  - Psychosocial health risk factors and resources of medical students and
      physicians: a cross-sectional study.
AB  - BACKGROUND: Epidemiological data indicate elevated psychosocial health risks for
      physicians, e. g., burnout, depression, marital disturbances, alcohol and
      substance abuse, and suicide. The purpose of this study was to identify
      psychosocial health resources and risk factors in profession-related behaviour
      and experience patterns of medical students and physicians that may serve as a
      basis for appropriate health promoting interventions. METHODS: The questionnaire 
      Related Behaviour and Experience "Work administered in cross-sectional surveys to
      students in the first (n = 475) and in the fifth year of studies (n = 355) in
      required courses at three German universities and to physicians in early
      professional life in the vicinity of these universities (n = 381). RESULTS:
      Scores reflecting a healthy behaviour pattern were less likely in physicians
      (16.7%) compared to 5th year (26.0%) and 1st year students (35.1%) while scores
      representing unambitious and resigned patterns were more common among physicians
      (43.4% vs. 24.4% vs. 41.0% and 27.3% vs. 17.2% vs. 23.3 respectively). Female and
      male responders differed in the domains professional commitment, resistance to
      stress and emotional well-being. Female physicians on average scored higher in
      the dimensions resignation tendencies, satisfaction with life and experience of
      social support, and lower in career ambition. CONCLUSION: The results show
      distinct psychosocial stress patterns among medical students and physicians.
      Health promotion and prevention of psychosocial symptoms and impairments should
      be integrated as a required part of the medical curriculum and be considered an
      important issue during the further training of physicians.

PMID- 18831733
TI  - Association of clinical findings in Yusho patients with serum concentrations of
      polychlorinated biphenyls, polychlorinated quarterphenyls and 2,3,4,7,8
      pentachlorodibenzofuran more than 30 years after the poisoning event.
AB  - BACKGROUND: The Yusho poisoning incident, which was caused by rice bran oil
      contaminated with polychlorinated biphenyls (PCBs), polychlorinated
      quarterphenyls (PCQs) and polychlorinated dibenzofurans (PCDFs) generated by heat
      denaturation of PCB, occurred in 1968 in western Japan. Annual physical,
      dermatological, dental, ophthalmological and laboratory examinations were
      conducted for Yusho patients after the incident. From 2001, blood levels of
      individual PCDF congeners were also measured. The blood levels of 2,3,4,7,8
      pentachlorodibenzofuran (2,3,4,7,8-PeCDF), PCBs and PCQs in Yusho patients were
      found to be significantly higher than those of the general population. We
      investigated the relationships between blood concentrations of 2,3,4,7,8-PeCDF,
      PCBs and PCQs in Yusho patients and the items measured in the annual medical
      examination. METHODS: Medical and laboratory examination data from 501 Yusho
      patients enrolled in the study from 2001 to 2004 were analyzed. The relationships
      between blood 2,3,4,7,8-PeCDF, PCB and PCQ concentrations and medical/laboratory
      examination data were investigated using principal components and logistic
      regression analyses. RESULTS: Serum Concentrations of 2,3,4,7,8-PeCDF, PCBs and
      PCQs in blood tended to correlate with either acneform eruptions, black
      comedones, cutaneous and mucosal pigmentation, and hypersecretion of meibomian
      glands as well as general fatigue, headaches, cough/sputum, abdominal pain,
      arthralgia, increased blood sugar, increased serum gamma-GTP and decreased total
      bilirubin. The majority of these signs and symptoms are included in the
      diagnostic criteria for Yusho. CONCLUSION: After Yusho patients had suffered
      chronic exposure to these chlorinated compounds for more than 35 years, the serum
      concentration of 2,3,4,7,8-PeCDF in blood was significantly related to arthralgia
      and decreased albumin/globulin (A/G) ratio; the serum concentration of PCBs was
      significantly related to ophthalmologic symptoms; and the serum concentration of
      PCQ to increased total cholesterol. These findings suggest that the co
      contaminants may affect other functions than those originally associated with
      Yusho.

PMID- 18831734
TI  - Evolutionary analysis of the highly dynamic CHEK2 duplicon in anthropoids.
AB  - BACKGROUND: Segmental duplications (SDs) are euchromatic portions of genomic DNA
      (> or = 1 kb) that occur at more than one site within the genome, and typically
      share a high level of sequence identity (>90%). Approximately 5% of the human
      genome is composed of such duplicated sequences. Here we report the detailed
      investigation of CHEK2 duplications. CHEK2 is a multiorgan cancer susceptibility
      gene encoding a cell cycle checkpoint kinase acting in the DNA-damage response
      signalling pathway. The continuous presence of the CHEK2 gene in all eukaryotes
      and its important role in maintaining genome stability prompted us to investigate
      the duplicative evolution and phylogeny of CHEK2 and its paralogs during
      anthropoid evolution. RESULTS: To study CHEK2 duplicon evolution in anthropoids
      we applied a combination of comparative FISH and in silico analyses. Our
      comparative FISH results with a CHEK2 fosmid probe revealed the single-copy
      status of CHEK2 in New World monkeys, Old World monkeys and gibbons. Whereas a
      single CHEK2 duplication was detected in orangutan, a multi-site signal pattern
      indicated a burst of duplication in African great apes and human. Phylogenetic
      analysis of paralogous and ancestral CHEK2 sequences in human, chimpanzee and
      rhesus macaque confirmed this burst of duplication, which occurred after the
      radiation of orangutan and African great apes. In addition, we used inter-species
      quantitative PCR to determine CHEK2 copy numbers. An amplification of CHEK2 was
      detected in African great apes and the highest CHEK2 copy number of all analysed
      species was observed in the human genome. Furthermore, we detected variation in
      CHEK2 copy numbers within the analysed set of human samples. CONCLUSION: Our
      detailed analysis revealed the highly dynamic nature of CHEK2 duplication during
      anthropoid evolution. We determined a burst of CHEK2 duplication after the
      radiation of orangutan and African great apes and identified the highest CHEK2
      copy number in human. In conclusion, our analysis of CHEK2 duplicon evolution
      revealed that SDs contribute to inter-species variation. Furthermore, our qPCR
      analysis led us to presume CHEK2 copy number variation in human, and molecular
      diagnostics of the cancer susceptibility gene CHEK2 inside the duplicated region
      might be hampered by the individual-specific set of duplicons.

PMID- 18831735
TI  - Towards a lightweight generic computational grid framework for biological
      research.
AB  - BACKGROUND: An increasing number of scientific research projects require access
      to large-scale computational resources. This is particularly true in the
      biological field, whether to facilitate the analysis of large high-throughput
      data sets, or to perform large numbers of complex simulations - a characteristic
      of the emerging field of systems biology. RESULTS: In this paper we present a
      lightweight generic framework for combining disparate computational resources at
      multiple sites (ranging from local computers and clusters to established national
      Grid services). A detailed guide describing how to set up the framework is
      available from the following URL: http://igrid-ext.cryst.bbk.ac.uk/portal_guide/.
      CONCLUSION: This approach is particularly (but not exclusively) appropriate for
      large-scale biology projects with multiple collaborators working at different
      national or international sites. The framework is relatively easy to set up,
      hides the complexity of Grid middleware from the user, and provides access to
      resources through a single, uniform interface. It has been developed as part of
      the European ImmunoGrid project.

PMID- 18831736
TI  - Splice-mediated Variants of Proteins (SpliVaP) - data and characterization of
      changes in signatures among protein isoforms due to alternative splicing.
AB  - BACKGROUND: It is often the case that mammalian genes are alternatively spliced;
      the resulting alternate transcripts often encode protein isoforms that differ in
      amino acid sequences. Changes among the protein isoforms can alter the cellular
      properties of proteins. The effect can range from a subtle modulation to a
      complete loss of function. RESULTS: (i) We examined human splice-mediated protein
      isoforms (as extracted from a manually curated data set, and from a
      computationally predicted data set) for differences in the annotation for protein
      signatures (Pfam domains and PRINTS fingerprints) and we characterized the
      differences & their effects on protein functionalities. An important question
      addressed relates to the extent of protein isoforms that may lack any known
      function in the cell. (ii) We present a database that reports differences in
      protein signatures among human splice-mediated protein isoform sequences.
      CONCLUSION: (i) Characterization: The work points to distinct sets of
      alternatively spliced genes with varying degrees of annotation for the splice
      mediated protein isoforms. Protein molecular functions seen to be often affected
      are those that relate to: binding, catalytic, transcription regulation,
      structural molecule, transporter, motor, and antioxidant; and the processes that
      are often affected are nucleic acid binding, signal transduction, and protein
      protein interactions. Signatures are often included/excluded and truncated in
      length among protein isoforms; truncation is seen as the predominant type of
      change. Analysis points to the following novel aspects: (a) Analysis using data
      from the manually curated Vega indicates that one in 8.9 genes can lead to a
      protein isoform of no "known" function; and one in 18 expressed protein isoforms
      can be such an "orphan" isoform; the corresponding numbers as seen with
      computationally predicted ASD data set are: one in 4.9 genes and one in 9.8
      isoforms. (b) When swapping of signatures occurs, it is often between those of
      same functional classifications. (c) Pfam domains can occur in varying lengths,
      and PRINTS fingerprints can occur with varying number of constituent motifs among
      isoforms - since such a variation is seen in large number of genes, it could be a
      general mechanism to modulate protein function. (ii) DATA: The reported resource
      (at http://www.bioinformatica.crs4.org/tools/dbs/splivap/) provides the community
      ability to access data on splice-mediated protein isoforms (with value-added
      annotation such as association with diseases) through changes in protein
      signatures.

PMID- 18831737
TI  - Impact of training in clinical and microscopy diagnosis of childhood malaria on
      antimalarial drug prescription and health outcome at primary health care level in
      Tanzania: a randomized controlled trial.
AB  - BACKGROUND: Prescribing antimalarial medicines based on parasite confirmed
      diagnosis of malaria is critical to rational drug use and optimal outcome of
      febrile illness. The impact of microscopy-based versus clinical-based diagnosis
      of childhood malaria was assessed at primary health care (PHC) facilities using a
      cluster randomized controlled training intervention trial. METHODS: Sixteen PHC
      facilities in rural Tanzania were randomly allocated to training of health staff
      in clinical algorithm plus microscopy (Arm-I, n = 5) or clinical algorithm only
      (Arm-II, n = 5) or no training (Arm-III, n = 6). Febrile under-five children
      presenting at these facilities were assessed, treated and scheduled for follow up
      visit after 7 days. Blood smears on day 0 were only done in Arm-I but on Day 7 in
      all arms. Primary outcome was antimalarial drug prescription. Other outcomes
      included antibiotic prescription and health outcome. Multilevel regression models
      were applied with PHC as level of clustering to compare outcomes in the three
      study arms. RESULTS: A total of 973, 1,058 and 1,100 children were enrolled in
      arms I, II and III, respectively, during the study period. Antimalarial
      prescriptions were significantly reduced in Arm-I (61.3%) compared to Arms-II
      (95.3%) and III (99.5%) (both P < 0.001), whereas antibiotic prescriptions did
      not vary significantly between the arms (49.9%, 54.8% and 34.2%, respectively).
      In Arm-I, 99.1% of children with positive blood smear readings received
      antimalarial prescriptions and so did 11.3% of children with negative readings.
      Those with positive readings were less likely to be prescribed antibiotics than
      those with negative (relative risk = 0.66, 95% confidence interval: 0.55, 0.72).
      On day 7 follow-up, more children reported symptoms in Arm-I compared to Arm-III,
      but fewer children had malaria parasitaemia (p = 0.049). The overall sensitivity
      of microscopy reading at PHC compared to reference level was 74.5% and the
      specificity was 59.0% but both varied widely between PHCs. CONCLUSION: Microscopy
      based diagnosis of malaria at PHC facilities reduces prescription of antimalarial
      drugs, and appears to improve appropriate management of non-malaria fevers, but
      major variation in accuracy of the microscopy readings was found. Lack of
      qualified laboratory technicians at PHC facilities and the relatively short
      training period may have contributed to the shortcomings. TRIAL REGISTRATION:
      This study is registered at Clinicaltrials.gov with the identifier NCT00687895.

PMID- 18831738
TI  - Selection and mutation on microRNA target sequences during rice evolution.
AB  - BACKGROUND: MicroRNAs (miRNAs) posttranscriptionally down-regulate gene
      expression by binding target mRNAs. Analysis of the evolution of miRNA binding
      sites is helpful in understanding the co-evolution between miRNAs and their
      targets. To understand this process in plants a comparative analysis of miRNA
      targeted duplicated gene pairs derived from a well-documented whole genome
      duplication (WGD) event in combination with a population genetics study of six
      experimentally validated miRNA binding sites in rice (O. sativa) was carried out.
      RESULTS: Of the 1,331 pairs of duplicate genes from the WGD, 41 genes (29 pairs)
      were computationally predicted to be miRNA targets. Sequence substitution
      analysis indicated that the synonymous substitution rate was significantly lower
      in the miRNA binding sites than their 5' and 3' flanking regions. Of the 29
      duplicated gene pairs, 17 have only one paralog been targeted by a miRNA. This
      could be due to either gain of a miRNA binding site after the WGD or because one
      of the duplicated genes has escaped from being a miRNA target after the WGD (loss
      of miRNA binding site). These possibilities were distinguished by separating
      miRNAs conserved in both dicots and monocot plants from rice-specific miRNAs and
      by phylogenetic analysis of miRNA target gene families. The gain/loss rate of
      miRNA binding sites was estimated to be 3.0 x 10(-9) gain/loss per year. Most
      (70.6%) of the gains/losses were due to nucleotide mutation. By analysis of
      cultivated (O. sativa; n = 30) and wild (O. rufipogon; n = 15) rice populations,
      no segregating site was observed in six miRNA binding sites whereas 0.12-0.20
      SNPs per 21-nt or 1.53-1.80 x 10(-3) of the average pairwise nucleotide diversity
      (pi) were found in their flanking regions. CONCLUSION: Both molecular evolution
      and population genetics support the hypothesis that conservation of miRNA binding
      sites is maintained by purifying selection through elimination of deleterious
      alleles. Nucleotide mutations play a major role in the gain/loss of miRNA binding
      sites during evolution.

PMID- 18831739
TI  - Chronic dislocation of proximal interphalangeal joint with mallet finger: A case
      report.
AB  - We report a case of chronic dislocation of proximal interphalangeal joint with
      mallet finger.

PMID- 18831740
TI  - Obesity and osteoarthritis in knee, hip and/or hand: an epidemiological study in
      the general population with 10 years follow-up.
AB  - BACKGROUND: Obesity is one of the most important risk factors for osteoarthritis
      (OA) in knee(s). However, the relationship between obesity and OA in hand(s) and
      hip(s) remains controversial and needs further investigation. The purpose of this
      study was to investigate the impact of obesity on incident osteoarthritis (OA) in
      hip, knee, and hand in a general population followed in 10 years. METHODS: A
      total of 1854 people aged 24-76 years in 1994 participated in a Norwegian study
      on musculoskeletal pain in both 1994 and 2004. Participants with OA or rheumatoid
      arthritis in 1994 and those above 74 years in 1994 were excluded, leaving n =
      1675 for the analyses. The main outcome measure was OA diagnosis at follow-up
      based on self-report. Obesity was defined by a body mass index (BMI) of 30 and
      above. RESULTS: At 10-years follow-up the incidence rates were 5.8% (CI 4.3-7.3)
      for hip OA, 7.3% (CI 5.7-9.0) for knee OA, and 5.6% (CI 4.2-7.1) for hand OA.
      When adjusting for age, gender, work status and leisure time activities, a high
      BMI (> 30) was significantly associated with knee OA (OR 2.81; 95%CI 1.32-5.96),
      and a dose-response relationship was found for this association. Obesity was also
      significantly associated with hand OA (OR 2.59; 1.08-6.19), but not with hip OA
      (OR 1.11; 0.41-2.97). There was no statistically significant interaction effect
      between BMI and gender, age or any of the other confounding variables.
      CONCLUSION: A high BMI was significantly associated with knee OA and hand OA, but
      not with hip OA.

PMID- 18831741
TI  - Adjacent thoracic lymph node metastases originating from two separate primary
      cancers: case report.
AB  - Reported is an unusual case of adjacent thoracic lymph nodes demonstrating
      metastases from two different primary malignancies. A 51 year-old woman with a
      previous history of bilateral breast cancer underwent a radical gastro
      oesophagectomy for adenocarcinoma of the lower third of the oesophagus. The
      resection specimen demonstrated breast and oesophageal metastases in adjacent
      thoracic lymph nodes. Mechanisms for this phenomenon, including the known local
      immune suppression on lymphoid cells by oesophageal carcinoma cells, are
      discussed.

PMID- 18831742
TI  - Predicting Global Fund grant disbursements for procurement of artemisinin-based
      combination therapies.
AB  - BACKGROUND: An accurate forecast of global demand is essential to stabilize the
      market for artemisinin-based combination therapy (ACT) and to ensure access to
      high-quality, life-saving medications at the lowest sustainable prices by
      avoiding underproduction and excessive overproduction, each of which can have
      negative consequences for the availability of affordable drugs. A robust forecast
      requires an understanding of the resources available to support procurement of
      these relatively expensive antimalarials, in particular from the Global Fund, at
      present the single largest source of ACT funding. METHODS: Predictive regression
      models estimating the timing and rate of disbursements from the Global Fund to
      recipient countries for each malaria grant were derived using a repeated split
      sample procedure intended to avoid over-fitting. Predictions were compared
      against actual disbursements in a group of validation grants, and forecasts of
      ACT procurement extrapolated from disbursement predictions were evaluated against
      actual procurement in two sub-Saharan countries. RESULTS: Quarterly forecasts
      were correlated highly with actual smoothed disbursement rates (r = 0.987, p <
      0.0001). Additionally, predicted ACT procurement, extrapolated from forecasted
      disbursements, was correlated strongly with actual ACT procurement supported by
      two grants from the Global Fund's first (r = 0.945, p < 0.0001) and fourth (r =
      0.938, p < 0.0001) funding rounds. CONCLUSION: This analysis derived predictive
      regression models that successfully forecasted disbursement patterning for
      individual Global Fund malaria grants. These results indicate the utility of this
      approach for demand forecasting of ACT and, potentially, for other commodities
      procured using funding from the Global Fund. Further validation using data from
      other countries in different regions and environments will be necessary to
      confirm its generalizability.

PMID- 18831743
TI  - The accuracy of MRI in the detection of lumbar disc containment.
AB  - BACKGROUND: MRI has proven to be an extremely valuable tool in the assessment of
      normal and pathological spinal anatomy. Accordingly, it is commonly used to
      assess containment of discal material by the outer fibers of the anulus fibrosus
      and posterior longitudinal ligaments. Determination of such containment is
      important to determine candidacy for intradiscal techniques and has prognostic
      significance. The accuracy of MRI in detecting containment has been
      insufficiently documented. METHODS: The MRI's of fifty consecutive patients
      undergoing open lumbar microdiscectomy were prospectively evaluated for disc
      containment by a neuroradiologist and senior spinal surgeon using criteria
      available in the literature and the classification of Macnab/McCulloch. An
      independent surgeon then performed the surgery and documented the actual
      containment status using the same methods. Statistical evaluation of accuracy was
      undertaken. RESULTS: MRI was found to be 72% sensitive, 68% specific, and 70%
      accurate in detecting containment status of lumbar herniated discs. CONCLUSION:
      MRI may be inaccurate in assessing containment status of lumbar disc herniations
      in 30% of cases. Given the importance of containment for patient selection for
      indirect discectomy techniques and intradiscal therapies, coupled with prognostic
      significance; other methods to assess containment should be employed to assess
      containment when such alternative interventions are being considered.

PMID- 18831744
TI  - Adalimumab improves health-related quality of life in patients with moderate to
      severe plaque psoriasis compared with the United States general population norms:
      results from a randomized, controlled Phase III study.
AB  - OBJECTIVE: To evaluate the impact of adalimumab on health-related quality of life
      (HRQOL) for patients with moderate to severe plaque psoriasis. BACKGROUND:
      Psoriasis is a chronic, inflammatory, immune-mediated disease that has a
      significant impact on patients' HRQOL. Adalimumab is a fully human monoclonal
      antibody that blocks tumor necrosis factor, a pro-inflammatory cytokine, and is
      effective and well-tolerated for patients with moderate to severe psoriasis.
      METHODS: Data were obtained for a secondary analysis of patients in a randomized,
      controlled Phase III trial evaluating the effect of adalimumab in patients with
      psoriasis (N = 1,205). Patients with moderate to severe psoriasis were randomized
      in a 2:1 ratio to adalimumab 80 mg (two 40 mg injections administered
      subcutaneously at baseline followed by one 40 mg injection every other week from
      Week 1 to Week 15) or placebo. Short Form-36 (SF-36) Health Survey scores of
      psoriasis patients were used to assess HRQOL and were compared with United States
      (US) population norms at baseline and Week 16. RESULTS: Baseline Physical
      Component Summary (PCS) scores for the placebo and adalimumab groups were similar
      to the general US population. Baseline mean Mental Component Summary (MCS) scores
      were significantly lower for the adalimumab and placebo groups compared with the
      general population (47.4, 47.7, and 50.8 points, respectively; p < 0.0001). PCS
      scores at Week 16 for patients receiving adalimumab had improved and were
      significantly greater than scores for the general US population (52.7 vs 48.9; p
      < 0.001). Compared with the general US population, MCS scores at Week 16 were
      similar for patients receiving adalimumab (51.2 vs 50.8; p = 1.000) and lower for
      patients receiving placebo (50.8 vs 48.7; p < 0.0001). CONCLUSION: Psoriasis has
      a broad impact on patient functioning and well-being. Improvement in skin lesions
      and joint symptoms associated with adalimumab treatment was accompanied by
      improvements in HRQOL to levels that were similar to or greater than those of the
      general US population. TRIAL REGISTRATION: Clinicaltrials.gov NCT00237887.

PMID- 18831745
TI  - Effects of self-management, education and specific exercises, delivered by health
      professionals, in patients with osteoarthritis of the knee.
AB  - BACKGROUND: An education self-management program for people with osteoarthritis
      (OA) of the knee was designed to be delivered by health professionals,
      incorporating their knowledge and expertise. Improvement in quality of life,
      health status and pain in response to this program has previously been
      demonstrated in an uncontrolled pilot study. To more rigorously test the
      effectiveness of the program we will undertake a randomised controlled trial of
      people with OA of the knee offering specific self-administered exercises and
      education, in accordance with the principles of self-management. AIM: To
      determine whether an education self management program for subjects with
      Osteoarthritis (OA) of the knee (OAK program) implemented by health professionals
      in a primary health care setting can achieve and maintain clinically meaningful
      improvements compared standard medical management in a control group. METHODS:
      The effects of standard medical management will be compared with the effects of
      the OAK program in a single-blind randomized study. PARTICIPANTS: 146 male and
      female participants with established OA knee will be recruited. Volunteers with
      coexistent inflammatory joint disease or serious co-morbidities will be excluded.
      INTERVENTIONS: Participants will be randomized into either intervention or
      control groups (delayed start). The intervention group will complete the OA knee
      program and both groups will be followed for 6 months. MEASUREMENTS: Assessments
      will be at baseline, 8 weeks and 6 months. SF-36, WOMAC and VAS pain
      questionnaires will be completed. Isometric quadriceps and hamstring strength
      will be measured using a dynamometer; knee range of movement using a goniometer;
      and physical function will be determined by a modified timed up and go test. Data
      will be analysed using repeated measures ANOVA. DISCUSSION: While there is
      evidence to support the effectiveness of SM programs for people with
      hypertension, diabetes and asthma, the evidence available for treatment of
      arthritis remains equivocal. The aim of this study is to determine the
      effectiveness of a disease specific self-management program for people with OA
      knee.The study design includes all the important features of a clinical
      experimental study to minimize bias so the results of the study will provide a
      high level of evidence. People with OA of the knee have identified pain and
      problems with daily activities as the most important problems associated with
      their condition. The outcome measures selected specifically address these issues
      and have demonstrated validity and are responsive within the range of change
      expected in response to the intervention. Hence the results of the study will
      reflect their priorities.The results of the study will provide evidence to guide
      clinicians and funding bodies seeking to establish priorities regarding the
      provision of this disease specific program. TRIAL REGISTRATION: ACTR number:
      12607000080426.

PMID- 18831746
TI  - Similarity of aberrant DNA methylation in Barrett's esophagus and esophageal
      adenocarcinoma.
AB  - BACKGROUND: Barrett's esophagus (BE) is the metaplastic replacement of squamous
      with columnar epithelium in the esophagus, as a result of reflux. It is the major
      risk factor for the development of esophageal adenocarcinoma (EAC). Methylation
      of CpG dinucleotides of normally unmethylated genes is associated with silencing
      of their expression, and is common in EAC. This study was designed to determine
      at what stage, in the progression from BE to EAC, methylation of key genes
      occurs. RESULTS: We examined nine genes (APC, CDKN2A, ID4, MGMT, RBP1, RUNX3,
      SFRP1, TIMP3, and TMEFF2), frequently methylated in multiple cancer types, in a
      panel of squamous (19 biopsies from patients without BE or EAC, 16 from patients
      with BE, 21 from patients with EAC), BE (40 metaplastic, seven high grade
      dysplastic) and 37 EAC tissues. The methylation frequency, the percentage of
      samples that had any extent of methylation, for each of the nine genes in the EAC
      (95%, 59%, 76%, 57%, 70%, 73%, 95%, 74% and 83% respectively) was significantly
      higher than in any of the squamous groups. The methylation frequency for each of
      the nine genes in the metaplastic BE (95%, 28%, 78%, 48%, 58%, 48%, 93%, 88% and
      75% respectively) was significantly higher than in the squamous samples except
      for CDKN2A and RBP1. The methylation frequency did not differ between BE and EAC
      samples, except for CDKN2A and RUNX3 which were significantly higher in EAC. The
      methylation extent was an estimate of both the number of methylated alleles and
      the density of methylation on these alleles. This was significantly greater in
      EAC than in metaplastic BE for all genes except APC, MGMT and TIMP3. There was no
      significant difference in methylation extent for any gene between high grade
      dysplastic BE and EAC. CONCLUSION: We found significant methylation in
      metaplastic BE, which for seven of the nine genes studied did not differ in
      frequency from that found in EAC. This is also the first report of gene silencing
      by methylation of ID4 in BE or EAC. This study suggests that metaplastic BE is a
      highly abnormal tissue, more similar to cancer tissue than to normal epithelium.

PMID- 18831747
TI  - Success with antiretroviral treatment for children in Kigali, Rwanda: experience
      with health center/nurse-based care.
AB  - BACKGROUND: Although a number of studies have shown good results in treating
      children with antiretroviral drugs (ARVs) in hospital settings, there is limited
      published information on results in pediatric programs that are nurse-centered
      and based in health centers, in particular on the psychosocial aspects of care.
      METHODS: Program treatment and outcome data were reported from two government-run
      health centers that were supported by Medecins Sans Frontieres (MSF) in Kigali,
      Rwanda between October 2003 and June 2007. Interviews were held with health
      center staff and MSF program records were reviewed to describe the organization
      of the program. Important aspects included adequate training and supervision of
      nurses to manage ARV treatment. The program also emphasized family-centered care
      addressing the psychosocial needs of both caregivers and children to encourage
      early diagnosis, good adherence and follow-up. RESULTS: A total of 315 children
      (< 15 years) were started on ARVs, at a median age of 7.2 years (range: 0.7
      14.9). Sixty percent were in WHO clinical stage I/II, with a median CD4% of 14%.
      Eighty-nine percent (n = 281) started a stavudine-containing regimen, mainly
      using the adult fixed-dose combination. The median follow-up time after ARV
      initiation was 2 years (interquartile range 1.2-2.6). Eighty-four percent (n =
      265) of children were still on treatment in the program. Thirty (9.5%) were
      transferred out, eight (2.6%) died and 12 (3.8%) were lost to follow-up. An
      important feature of the study was that viral loads were done at a median time
      period of 18 months after starting ARVs and were available for 87% of the
      children. Of the 174 samples, VL was < 400 copies/ml in 82.8% (n = 144). Two
      children were started on second-line ARVs. Treatment was changed due to toxicity
      for 26 children (8.3%), mainly related to nevirapine. CONCLUSION: This report
      suggests that providing ARVs to children in a health center/nurse-based program
      is both feasible and very effective. Adequate numbers and training of nursing
      staff and an emphasis on the psychosocial needs of caregivers and children have
      been key elements for the successful scaling-up of ARVs at this level of the
      health system.

PMID- 18831748
TI  - Partitioning the population attributable fraction for a sequential chain of
      effects.
AB  - BACKGROUND: While the population attributable fraction (PAF) provides potentially
      valuable information regarding the community-level effect of risk factors,
      significant limitations exist with current strategies for estimating a PAF in
      multiple risk factor models. These strategies can result in paradoxical or
      ambiguous measures of effect, or require unrealistic assumptions regarding
      variables in the model. A method is proposed in which an overall or total PAF
      across multiple risk factors is partitioned into components based upon a
      sequential ordering of effects. This method is applied to several hypothetical
      data sets in order to demonstrate its application and interpretation in diverse
      analytic situations. RESULTS: The proposed method is demonstrated to provide
      clear and interpretable measures of effect, even when risk factors are
      related/correlated and/or when risk factors interact. Furthermore, this strategy
      not only addresses, but also quantifies issues raised by other researchers who
      have noted the potential impact of population-shifts on population-level effects
      in multiple risk factor models. CONCLUSION: Combined with simple, unadjusted PAF
      estimates and an aggregate PAF based on all risk factors under consideration, the
      sequentially partitioned PAF provides valuable additional information regarding
      the process through which population rates of a disorder may be impacted. In
      addition, the approach can also be used to statistically control for confounding
      by other variables, while avoiding the potential pitfalls of attempting to
      separately differentiate direct and indirect effects.

PMID- 18831749
TI  - Echinacea purpurea and osteopathic manipulative treatment in children with
      recurrent otitis media: a randomized controlled trial.
AB  - BACKGROUND: Recurrent otitis media is a common problem in young children.
      Echinacea and osteopathic manipulative treatment have been proposed as preventive
      measures, but have been inadequately studied. This study was designed to assess
      the efficacy of Echinacea purpurea and/or osteopathic manipulative treatment
      (OMT) for prevention of acute otitis media in otitis-prone children. METHODS: A
      randomized, placebo-controlled, two-by-two factorial trial with 6-month follow
      up, conducted 1999 - 2002 in Tucson, Arizona. Patients were aged 12-60 months
      with recurrent otitis media, defined as three or more separate episodes of acute
      otitis media within six months, or at least four episodes in one year. Ninety
      children (44% white non-Hispanic, 39% Hispanic, 57% male) were enrolled, of which
      84 had follow-up for at least 3 months. Children were randomly assigned to one of
      four protocol groups: double placebo, echinacea plus sham OMT, true OMT
      (including cranial manipulation) plus placebo echinacea, or true echinacea plus
      OMT. An alcohol extract of Echinacea purpurea roots and seeds (or placebo) was
      administered for 10 days at the first sign of each common cold. Five OMT visits
      (or sham treatments) were offered over 3 months. RESULTS: No interaction was
      found between echinacea and OMT. Echinacea was associated with a borderline
      increased risk of having at least one episode of acute otitis media during 6
      month follow-up compared to placebo (65% versus 41%; relative risk, 1.59, 95% CI
      1.04, 2.42). OMT did not significantly affect risk compared to sham (44% versus
      61%; relative risk, 0.72, 95% CI 0.48, 1.10). CONCLUSION: In otitis-prone young
      children, treating colds with this form of echinacea does not decrease the risk
      of acute otitis media, and may in fact increase risk. A regimen of up to five
      osteopathic manipulative treatments does not significantly decrease the risk of
      acute otitis media. TRIAL REGISTRATION: ClinicalTrials.gov Identifier:
      NCT00010465.

PMID- 18831750
TI  - Key biosynthetic gene subfamily recruited for pheromone production prior to the
      extensive radiation of Lepidoptera.
AB  - BACKGROUND: Moths have evolved highly successful mating systems, relying on
      species-specific mixtures of sex pheromone components for long-distance mate
      communication. Acyl-CoA desaturases are key enzymes in the biosynthesis of these
      compounds and to a large extent they account for the great diversity of pheromone
      structures in Lepidoptera. A novel desaturase gene subfamily that displays
      Delta11 catalytic activities has been highlighted to account for most of the
      unique pheromone signatures of the taxonomically advanced ditrysian species. To
      assess the mechanisms driving pheromone evolution, information is needed about
      the signalling machinery of primitive moths. The currant shoot borer, Lampronia
      capitella, is the sole reported primitive non-ditrysian moth known to use
      unsaturated fatty-acid derivatives as sex-pheromone. By combining biochemical and
      molecular approaches we elucidated the biosynthesis paths of its main pheromone
      component, the (Z,Z)-9,11-tetradecadien-1-ol and bring new insights into the time
      point of the recruitment of the key Delta11-desaturase gene subfamily in moth
      pheromone biosynthesis. RESULTS: The reconstructed evolutionary tree of
      desaturases evidenced two ditrysian-specific lineages (the Delta11 and Delta9
      (18C>16C)) to have orthologs in the primitive moth L. capitella despite being
      absent in Diptera and other insect genomes. Four acyl-CoA desaturase cDNAs were
      isolated from the pheromone gland, three of which are related to Delta9
      desaturases whereas the fourth cDNA clusters with Delta11-desaturases. We
      demonstrated that this transcript (Lca-KPVQ) exclusively accounts for both steps
      of desaturation involved in pheromone biosynthesis. This enzyme possesses a Z11
      desaturase activity that allows transforming the palmitate precursor (C16:0) into
      (Z)-11-hexadecenoic acid and the (Z)-9-tetradecenoic acid into the conjugated
      intermediate (Z,Z)-9,11-tetradecadienoic acid. CONCLUSION: The involvement of a
      single Z11-desaturase in pheromone biosynthesis of a non-ditrysian moth species,
      supports that the duplication event leading to the origin of the Lepidoptera
      specific Delta11-desaturase gene subfamily took place before radiation of
      ditrysian moths and their divergence from other heteroneuran lineages. Our
      findings uncover that this novel class of enzymes affords complex combinations of
      unique unsaturated fatty acyl-moieties of variable chain-lengths, regio- and
      stereo-specificities since early in moth history and contributes a notable
      innovation in the early evolution of moth-pheromones.

PMID- 18831751
TI  - Breast and bowel cancer screening uptake patterns over 15 years for UK south
      Asian ethnic minority populations, corrected for differences in socio-demographic
      characteristics.
AB  - BACKGROUND: A number of studies have reported low uptake of cancer screening
      programmes by South Asian populations in the UK. However, studies to date have
      not adjusted findings for differences in demographics and socio-economic status
      of these populations. METHODS:  SUBJECTS: All residents in Coventry and
      Warwickshire, UK, eligible for screening. Uptakes compared for round 1 (2000-02)
      and round 2 (2003-05) of a national bowel cancer screening pilot, and for rounds
      1, 2 and 5 of the established NHS breast cancer screening programme (commenced
      1989). DATA: Bowel screening data were analysed for 123,367 invitees in round 1
      and 116,773 in round 2 (total 240,140 cases). Breast screening data were analysed
      for 61,934, 62,829 and 86,749 invitees in rounds 1, 2 and 5 respectively (total
      211,512 cases). ANALYSIS: Screening uptake was compared for two broad meta
      categories (South Asian and non-Asian) and for five Asian subgroups (Hindu
      Gujarati; Hindu-Other; Muslim; Sikh; South Asian Other). Univariate and
      multivariate analyses examined screening uptake and various demographic
      attributes of invitees, including age, gender, deprivation and ethnic group.
      RESULTS: South Asians demonstrated significantly lower (p < 0.001) unadjusted
      bowel screening uptake; 32.8% vs. 61.3% for non-Asians (round 1). Rates were
      particularly low for the Muslim subgroup: 26.1% (round 1), 21.5% (round 2). For
      breast screening, a smaller difference was observed between South Asians and non
      Asians; initially 60.8% vs. 75.4% (round 1) and later 66.8% vs. 77.7% (round 5).
      Thus, the disparity reduced gradually over time, alongside an overall trend of
      increased uptake. However, figures remained consistently low for Muslims (51% in
      rounds 1 and 5). After adjusting for age, deprivation (and gender), bowel
      screening uptake remained significantly lower for all South Asian subgroups.
      After similar adjustments, breast screening uptake remained lower for all
      subgroups except Hindu-Gujaratis. For Muslims registered with an Asian (vs. non
      Asian) GP, bowel screening uptake was significantly lower (p < 0.001). However,
      breast screening uptake for Muslims with an Asian (vs. non-Asian) GP showed no
      difference (p = 0.12) in the same period. Colonoscopy and breast assessment
      uptakes were similar for both meta-categories, but Asian response time appeared
      slower for colonoscopy. The percentage of abnormal FOBT results was significantly
      higher for South Asian invitees. A slight increase in abnormal mammograms was
      observed for Muslims over time (2.7% to 4.2% in rounds 1 and 5 respectively).
      CONCLUSION: The lower cancer screening uptakes observed for the South Asian
      population cannot be attributed to socio-economic, age or gender population
      differences. Although breast screening disparities have reduced over time,
      significant differences remain. We conclude that both programmes need to
      implement and assess interventions to reduce such differences.

PMID- 18831752
TI  - Milk: the new sports drink? A Review.
AB  - There has been growing interest in the potential use of bovine milk as an
      exercise beverage, especially during recovery from resistance training and
      endurance sports. Based on the limited research, milk appears to be an effective
      post-resistance exercise beverage that results in favourable acute alterations in
      protein metabolism. Milk consumption acutely increases muscle protein synthesis,
      leading to an improved net muscle protein balance. Furthermore, when post
      exercise milk consumption is combined with resistance training (12 weeks
      minimum), greater increases in muscle hypertrophy and lean mass have been
      observed. Although research with milk is limited, there is some evidence to
      suggest that milk may be an effective post-exercise beverage for endurance
      activities. Low-fat milk has been shown to be as effective, if not more
      effective, than commercially available sports drinks as a rehydration beverage.
      Milk represents a more nutrient dense beverage choice for individuals who partake
      in strength and endurance activities, compared to traditional sports drinks.
      Bovine low-fat fluid milk is a safe and effective post exercise beverage for most
      individuals, except for those who are lactose intolerant. Further research is
      warranted to better delineate the possible applications and efficacy of bovine
      milk in the field of sports nutrition.

PMID- 18831753
TI  - Unassigned MURF1 of kinetoplastids codes for NADH dehydrogenase subunit 2.
AB  - BACKGROUND: In a previous study, we conducted a large-scale similarity-free
      function prediction of mitochondrion-encoded hypothetical proteins, by which the
      hypothetical gene murf1 (maxicircle unidentified reading frame 1) was assigned as
      nad2, encoding subunit 2 of NADH dehydrogenase (Complex I of the respiratory
      chain). This hypothetical gene occurs in the mitochondrial genome of
      kinetoplastids, a group of unicellular eukaryotes including the causative agents
      of African sleeping sickness and leishmaniasis. In the present study, we test
      this assignment by using bioinformatics methods that are highly sensitive in
      identifying remote homologs and confront the prediction with available biological
      knowledge. RESULTS: Comparison of MURF1 profile Hidden Markov Model (HMM) against
      function-known profile HMMs in Pfam, Panther and TIGR shows that MURF1 is a
      Complex I protein, but without specifying the exact subunit. Therefore, we
      constructed profile HMMs for each individual subunit, using all available
      sequences clustered at various identity thresholds. HMM-HMM comparison of these
      individual NADH subunits against MURF1 clearly identifies this hypothetical
      protein as NAD2. Further, we collected the relevant experimental information
      about kinetoplastids, which provides additional evidence in support of this
      prediction. CONCLUSION: Our in silico analyses provide convincing evidence for
      MURF1 being a highly divergent member of NAD2.

PMID- 18831754
TI  - Recovering probabilities for nucleotide trimming processes for T cell receptor
      TRA and TRG V-J junctions analyzed with IMGT tools.
AB  - BACKGROUND: Nucleotides are trimmed from the ends of variable (V), diversity (D)
      and joining (J) genes during immunoglobulin (IG) and T cell receptor (TR)
      rearrangements in B cells and T cells of the immune system. This trimming is
      followed by addition of nucleotides at random, forming the N regions (N for
      nucleotides) of the V-J and V-D-J junctions. These processes are crucial for
      creating diversity in the immune response since the number of trimmed nucleotides
      and the number of added nucleotides vary in each B or T cell. IMGT sequence
      analysis tools, IMGT/V-QUEST and IMGT/JunctionAnalysis, are able to provide
      detailed and accurate analysis of the final observed junction nucleotide
      sequences (tool "output"). However, as trimmed nucleotides can potentially be
      replaced by identical N region nucleotides during the process, the observed
      "output" represents a biased estimate of the "true trimming process." RESULTS: A
      probabilistic approach based on an analysis of the standardized tool "output" is
      proposed to infer the probability distribution of the "true trimmming process"
      and to provide plausible biological hypotheses explaining this process. We
      collated a benchmark dataset of TR alpha (TRA) and TR gamma (TRG) V-J rearranged
      sequences and junctions analysed with IMGT/V-QUEST and IMGT/JunctionAnalysis, the
      nucleotide sequence analysis tools from IMGT, the international ImMunoGeneTics
      information system, http://imgt.cines.fr. The standardized description of the
      tool output is based on the IMGT-ONTOLOGY axioms and concepts. We propose a
      simple first-order model that attempts to transform the observed "output"
      probability distribution into an estimate closer to the "true trimming process"
      probability distribution. We use this estimate to test the hypothesis that
      Poisson processes are involved in trimming. This hypothesis was not rejected at
      standard confidence levels for three of the four trimming processes: TRAV, TRAJ
      and TRGV. CONCLUSION: By using trimming of rearranged TR genes as a benchmark, we
      show that a probabilistic approach, applied to IMGT standardized tool "outputs"
      opens the way to plausible hypotheses on the events involved in the "true
      trimming process" and eventually to an exact quantification of trimming itself.
      With increasing high-throughput of standardized immunogenetics data, similar
      probabilistic approaches will improve understanding of processes so far only
      characterized by the "output" of standardized tools.

PMID- 18831755
TI  - Huge incisional hernia: A case report.
AB  - INTRODUCTION: The incidence of incisional hernia depends on many factors factors
      including old age, sex, obesity, bowel surgery, suture type, chest infection,
      abdominal distension and wound infection. CASE REPORT: A 55 years old woman
      presented at out institute, she had an operation 19 years ago - elsewhere - to
      remove a branched stone from her right kidney and admitted for two months into
      the hospital at this time as she had troubles with her surgical wound and she had
      repeated secondary sutures. The hernia is in the right lumbar region, has a
      smooth surface, shows expansile impulse on coughing, there are some dilated veins
      on its surface, there is no tenderness, it has a uniform consistency, mobile,
      there are no pulsations, it contains large and small intestine, partially
      reducible, the defect is about 10 cm in diameter and there are no complications.
      This woman had left nephrectomy two years ago as a treatment for painful non
      functioning kidney and she is living now with only functioning right kidney with
      serum creatinine 1.1 mg % and blood urea 38 mg %. CONCLUSION: Incisional hernia
      is a very common complication of wound healing after surgery. Good care and
      precautions are very important to avoid its development.

PMID- 18831756
TI  - Rapid progression of traumatic bifrontal contusions to transtentorial herniation:
      A case report.
AB  - We report a case of mild to moderate traumatic brain injury in which ICP
      monitoring or quantitative cerebral perfusion data may have allowed earlier
      recognition of impending herniation, avoidance of a secondary insult, and
      ultimately resulted in a better outcome, even though the patient did not meet the
      standard guidelines of the Brain Trauma Foundation. A thirty-five year old male
      who presented with traumatic bifrontal contusions and GCS of fourteen and twelve
      hours later progressed rapidly to having dilated pupils and
      transtentorial/central herniation over the course of fifteen minutes. The patient
      was taken emergently for a bifrontal craniectomy. Post operatively he had an
      acute infarct in the posterolateral left temporal lobe with expected evolution of
      parenchymal contusions as well as infarcts in the splenium of the corpus
      callosum, left thalamus and medial right occipital lobe. This case signifies an
      exception from the guidelines submitted by the Brain Trauma Foundation for
      intracranial pressure monitoring in patients with severe brain injury.We also
      point out previous reports which state that in such a patient a more sensitive
      test for detection would perhaps be quantitative blood flow monitoring, and may
      have led to a better outcome. We recommend using intracranial pressure monitoring
      or blood flow measurements to trend patients with bifrontal intraparenchymal
      contusions and GCS greater than eight to prevent clinically undetected
      deterioration from transtentorial/central herniation.

PMID- 18831757
TI  - Normalization of Illumina Infinium whole-genome SNP data improves copy number
      estimates and allelic intensity ratios.
AB  - BACKGROUND: Illumina Infinium whole genome genotyping (WGG) arrays are
      increasingly being applied in cancer genomics to study gene copy number
      alterations and allele-specific aberrations such as loss-of-heterozygosity (LOH).
      Methods developed for normalization of WGG arrays have mostly focused on diploid,
      normal samples. However, for cancer samples genomic aberrations may confound
      normalization and data interpretation. Therefore, we examined the effects of the
      conventionally used normalization method for Illumina Infinium arrays when
      applied to cancer samples. RESULTS: We demonstrate an asymmetry in the detection
      of the two alleles for each SNP, which deleteriously influences both allelic
      proportions and copy number estimates. The asymmetry is caused by a remaining
      bias between the two dyes used in the Infinium II assay after using the
      normalization method in Illumina's proprietary software (BeadStudio). We propose
      a quantile normalization strategy for correction of this dye bias. We tested the
      normalization strategy using 535 individual hybridizations from 10 data sets from
      the analysis of cancer genomes and normal blood samples generated on Illumina
      Infinium II 300 k version 1 and 2, 370 k and 550 k BeadChips. We show that the
      proposed normalization strategy successfully removes asymmetry in estimates of
      both allelic proportions and copy numbers. Additionally, the normalization
      strategy reduces the technical variation for copy number estimates while
      retaining the response to copy number alterations. CONCLUSION: The proposed
      normalization strategy represents a valuable tool that improves the quality of
      data obtained from Illumina Infinium arrays, in particular when used for LOH and
      copy number variation studies.

PMID- 18831758
TI  - Acute hepatic failure due to dengue: A case report.
AB  - Dengue is an arboviral disease endemic in many parts of the world. Although it
      is known to cause hepatic involvement commonly, it only occasionally results in
      acute hepatic failure. We present the case of a young male who developed acute
      hepatic failure due to dengue. The differentials and the management is discussed.

PMID- 18831759
TI  - Alpha-2 adrenergic-induced changes in rectal temperature in adult and 13-day old
      rats following acute and repeated desipramine administration.
AB  - BACKGROUND: The effects of acute and repeated treatment with desipramine on the
      functional response of alpha2-adrenoceptors were tested in adult and 13-day old
      rats. The functional response measured was hypothermia that was induced by
      brimonidine, an alpha2-adrenoceptor agonist. The change in the extent of the
      brimonidine-induced hypothermia following pretreatment with either single or 4
      twice-daily injections of desipramine was compared in 13-day old and adult (65-75
      days old) male rats. RESULTS: Brimonidine, alone, lowered rectal temperature to a
      greater extent in juvenile than in adult rats, and this response was dose
      dependently blocked by the selective alpha2-adrenoceptor antagonist, RX821002, in
      both groups of rats. Single desipramine administration lowered rectal temperature
      in the absence of brimonidine in adult but not in juvenile rats. The adult rats
      developed tolerance to this hypothermic effect after 4 days of desipramine
      treatment (10 mg/kg twice daily). Repeated desipramine treatment of adult rats
      also resulted in an enhancement in the brimonidine-induced hypothermic effect 24
      h after the last dose, a time when above 90% of desipramine and its metabolite,
      desmethyldesipramine, had cleared the brain, but not at 14, 48 or 96 h after the
      last dose. In juvenile rats repeated injections of desipramine (3 mg/kg twice
      daily for 4 days) had no effect on the alpha2-agonist-induced hypothermia when
      brimonidine was given 14, 24, 63 and 96 h after the last dose of desipramine.
      CONCLUSION: The results suggest that juvenile rats response differently than
      adult rats to agonist stimulation of alpha2-adrenoceptors with and without
      pretreatment with the antidepressant desipramine. In the absence of desipramine
      pretreatment, the alpha2-adrenoceptor-induced hypothermic effect in juvenile rats
      is greater than in adult rats. Acute injections of desipramine, in the absence of
      agonist produced a hypothermic effect in adult but not juvenile rats. In
      addition, the increased alpha2-agonist-induced hypothermic effect following
      repeated injections of desipramine that is seen in adult rats is not seen in
      juvenile rats.

PMID- 18831760
TI  - The Mycoplasma pneumoniae MPN229 gene encodes a protein that selectively binds
      single-stranded DNA and stimulates Recombinase A-mediated DNA strand exchange.
AB  - BACKGROUND: Mycoplasma pneumoniae has previously been characterized as a micro
      organism that is genetically highly stable. In spite of this genetic stability,
      homologous DNA recombination has been hypothesized to lie at the basis of
      antigenic variation of the major surface protein, P1, of M. pneumoniae. In order
      to identify the proteins that may be involved in homologous DNA recombination in
      M. pneumoniae, we set out to characterize the MPN229 open reading frame (ORF),
      which bears sequence similarity to the gene encoding the single-stranded DNA
      binding (SSB) protein of other micro-organisms. RESULTS: The MPN229 ORF has the
      capacity to encode a 166-amino acid protein with a calculated molecular mass of
      18.4 kDa. The amino acid sequence of this protein (Mpn SSB) is most closely
      related to that of the protein predicted to be encoded by the MG091 gene from
      Mycoplasma genitalium (61% identity). The MPN229 ORF was cloned, and different
      versions of Mpn SSB were expressed in E. coli and purified to > 95% homogeneity.
      The purified protein was found to exist primarily as a homo-tetramer in solution,
      and to strongly and selectively bind single-stranded DNA (ssDNA) in a divalent
      cation- and DNA substrate sequence-independent manner. Mpn SSB was found to bind
      with a higher affinity to ssDNA substrates larger than 20 nucleotides than to
      smaller substrates. In addition, the protein strongly stimulated E. coli
      Recombinase A (RecA)-promoted DNA strand exchange, which indicated that Mpn SSB
      may play an important role in DNA recombination processes in M. pneumoniae.
      CONCLUSION: The M. pneumoniae MPN229 gene encodes a protein, Mpn SSB, which
      selectively and efficiently binds ssDNA, and stimulates E. coli RecA-promoted
      homologous DNA recombination. Consequently, the Mpn SSB protein may play a
      crucial role in DNA recombinatorial pathways in M. pneumoniae. The results from
      this study will pave the way for unraveling these pathways and assess their role
      in antigenic variation of M. pneumoniae.

PMID- 18831761
TI  - 'Rapunzel syndrome' trichobezoar in a 7-year-old girl: a case report.
AB  - BACKGROUND: Rapunzel syndrome is a rare type of trichobezoar with an extension of
      the hair into the small bowel. Clinical presentation is deceptive and vague
      ranging from abdominal mass to gastrointestinal symptoms. CASE PRESENTATION: We
      present a 7 years old girl with Rapunzel syndrome, where the trichobezoar was not
      suspected at all especially with negative history of trichophagia. In majority of
      the cases the diagnosis was made very late in the history of the disease, at a
      stage where surgery is the only cure for this syndrome. CONCLUSION: In the
      paediatric age group with a long history of gastrointestinal symptom, endoscopy
      is a diagnostic as well as a therapeutic modality and may reduce surgery in
      trichobezoars.

PMID- 18831762
TI  - Adenomatoid tumor of epididymidis: A case report.
AB  - BACKGROUND: Adenomatoid tumors are regarded as distinctive benign mesothelial
      neoplasms of the paratesticular region, most commonly occuring at the tail of the
      epididymidis.Because of its rarity, the clinical and histopathological aspects
      are discussed. CASE PRESENTATION: We present the case of a 41-year-old patient
      with an adenomatoid tumour located in the tail of the left epididymis that
      referred to our department with gradual enlarged intrascrotal mass. The diagnosis
      was achieved by echography, and was confirmed by surgical excision and
      histological analysis. CONCLUSION: Due to its low incidence in intrascrotal
      pathology, we believe it is important for the physician to be aware of this
      interesting entity in order to make a differential diagnosis from other
      inflammatory processes and to adopt the proper surgical approach.

PMID- 18831763
TI  - IgM multiple myeloma presenting with spinal cord compression caused by a
      plasmacytoma: A case report.
AB  - BACKGROUND: IgM multiple myeloma is rare disorder, which has clinical, laboratory
      and radiological manifestations that are consistent with both multiple myeloma
      and Waldenstrom's macroglobulinaemia. CASE PRESENTATION: An 83 years Welsh lady
      presented with clinical and radiological features consistent with spinal cord
      compression. Further investigations confirmed the diagnosis of IgM multiple
      myeloma. Following localized radiotherapy and five courses of melphalan and
      prednisolone, the patient achieved partial remission of her myeloma. Later on,
      the patient had disease progression in the form of rising serum IgM level and the
      development of multiple plasmacytomas. She was treated with thalidomide,
      cyclophosphamide, dexamethasone and radiotherapy, which resulted in the control
      of her disease for one year. To our knowledge, this is the second case of IgM
      myeloma presenting with a plasmacytoma and the first case of IgM myeloma
      presenting with cord compression caused by plasmacytomas. CONCLUSION: Unlike
      other types of multiple myeloma IgM myeloma is rarely complicated by
      plasmacytomas. However, spinal cord compression caused by plasmacytomas in this
      type of myeloma is extremely rare. Nevertheless, the same lines of management,
      e.g. cytotoxic chemotherapy and local radiotherapy that are applied to other
      types of myeloma can be successfully utilized.

PMID- 18831764
TI  - Transsynaptic transport of wheat germ agglutinin expressed in a subset of type II
      taste cells of transgenic mice.
AB  - BACKGROUND: Anatomical tracing of neural circuits originating from specific
      subsets of taste receptor cells may shed light on interactions between taste
      cells within the taste bud and taste cell-to nerve interactions. It is unclear
      for example, if activation of type II cells leads to direct activation of the
      gustatory nerves, or whether the information is relayed through type III cells.
      To determine how WGA produced in T1r3-expressing taste cells is transported into
      gustatory neurons, transgenic mice expressing WGA-IRES-GFP driven by the T1r3
      promoter were generated. RESULTS: Immunohistochemistry showed co-expression of
      WGA, GFP and endogenous T1r3 in the taste bud cells of transgenic mice: the only
      taste cells immunoreactive for WGA were the T1r3-expressing cells. The WGA
      antibody also stained intragemmal nerves. WGA, but not GFP immunoreactivity was
      found in the geniculate and petrosal ganglia of transgenic mice, indicating that
      WGA was transported across synapses. WGA immunoreactivity was also found in the
      trigeminal ganglion, suggesting that T1r3-expressing cells make synapses with
      trigeminal neurons. In the medulla, WGA was detected in the nucleus of the
      solitary tract but also in the nucleus ambiguus, the vestibular nucleus, the
      trigeminal nucleus and in the gigantocellular reticular nucleus. WGA was not
      detected in the parabrachial nucleus, or the gustatory cortex. CONCLUSION: These
      results show the usefulness of genetically encoded WGA as a tracer for the first
      and second order neurons that innervate a subset of taste cells, but not for
      higher order neurons, and demonstrate that the main route of output from type II
      taste cells is the gustatory neuron, not the type III cells.

PMID- 18831765
TI  - An unexpectedly high degree of specialization and a widespread involvement in
      sterol metabolism among the C. elegans putative aminophospholipid translocases.
AB  - BACKGROUND: P-type ATPases in subfamily IV are exclusively eukaryotic
      transmembrane proteins that have been proposed to directly translocate the
      aminophospholipids phosphatidylserine and phosphatidylethanolamine from the
      exofacial to the cytofacial monolayer of the plasma membrane. Eukaryotic genomes
      contain many genes encoding members of this subfamily. At present it is unclear
      why there are so many genes of this kind per organism or what individual roles
      these genes perform in organism development. RESULTS: We have systematically
      investigated expression and developmental function of the six, tat-1 through 6,
      subfamily IV P-type ATPase genes encoded in the Caenorhabditis elegans genome.
      tat-5 is the only ubiquitously-expressed essential gene in the group. tat-6 is a
      poorly-transcribed recent duplicate of tat-5. tat-2 through 4 exhibit tissue
      specific developmentally-regulated expression patterns. Strong expression of both
      tat-2 and tat-4 occurs in the intestine and certain other cells of the alimentary
      system. The two are also expressed in the uterus, during spermatogenesis and in
      the fully-formed spermatheca. tat-2 alone is expressed in the pharyngeal gland
      cells, the excretory system and a few cells of the developing vulva. The
      expression pattern of tat-3 is almost completely different from those of tat-2
      and tat-4. tat-3 expression is detectable in the steroidogenic tissues: the
      hypodermis and the XXX cells, as well as in most cells of the pharynx (except
      gland), various tissues of the reproductive system (except uterus and
      spermatheca) and seam cells. Deletion of tat-1 through 4 individually interferes
      little or not at all with the regular progression of organism growth and
      development under normal conditions. However, tat-2 through 4 become essential
      for reproductive growth during sterol starvation. CONCLUSION: tat-5 likely
      encodes a housekeeping protein that performs the proposed aminophospholipid
      translocase function routinely. Although individually dispensable, tat-1 through
      4 seem to be at most only partly redundant. Expression patterns and the sterol
      deprivation hypersensitivity deletion phenotype of tat-2 through 4 suggest that
      these genes carry out subtle metabolic functions, such as fine-tuning sterol
      metabolism in digestive or steroidogenic tissues. These findings uncover an
      unexpectedly high degree of specialization and a widespread involvement in sterol
      metabolism among the genes encoding the putative aminophospholipid translocases.

PMID- 18831766
TI  - Factors influencing the adoption of an innovation: an examination of the uptake
      of the Canadian Heart Health Kit (HHK).
AB  - BACKGROUND: There is an emerging knowledge base on the effectiveness of
      strategies to close the knowledge-practice gap. However, less is known about how
      attributes of an innovation and other contextual and situational factors
      facilitate and impede an innovation's adoption. The Healthy Heart Kit (HHK) is a
      risk management and patient education resource for the prevention of
      cardiovascular disease (CVD) and promotion of cardiovascular health. Although
      previous studies have demonstrated the HHK's content validity and practical
      utility, no published study has examined physicians' uptake of the HHK and
      factors that shape its adoption. OBJECTIVES: Conceptually informed by Rogers'
      Diffusion of Innovation theory, and Theory of Planned Behaviour, this study had
      two objectives: (1) to determine if specific attributes of the HHK as well as
      contextual and situational factors are associated with physicians' intention and
      actual usage of the HHK kit; and (2), to determine if any contextual and
      situational factors are associated with individual or environmental barriers that
      prevent the uptake of the HHK among those physicians who do not plan to use the
      kit. METHODS: A sample of 153 physicians who responded to an invitation letter
      sent to all family physicians in the province of Alberta, Canada were recruited
      for the study. Participating physicians were sent a HHK, and two months later a
      study questionnaire assessed primary factors on the physicians' clinical
      practice, attributes of the HHK (relative advantage, compatibility, complexity,
      trialability, observability), confidence and control using the HHK, barriers to
      use, and individual attributes. All measures were used in path analysis,
      employing a causal model based on Rogers' Diffusion of Innovations Theory and
      Theory of Planned Behaviour. RESULTS: 115 physicians (follow up rate of 75%)
      completed the questionnaire. Use of the HHK was associated with intention to use
      the HHK, relative advantage, and years of experience. Relative advantage and the
      observability of the HHK benefits were also significantly associated with
      physicians' intention to use the HHK. Physicians working in solo medical
      practices reported experiencing more individual and environmental barriers to
      using the HHK. CONCLUSION: The results of this study suggest that future
      information innovations must demonstrate an advantage over current resources and
      the research evidence supporting the innovation must be clearly visible. Findings
      also suggest that the innovation adoption process has a social element, and
      collegial interactions and discussions may facilitate that process. These results
      could be valuable for knowledge translation researchers and health promotion
      developers in future innovation adoption planning.

PMID- 18831767
TI  - Does creatine supplementation improve the plasma lipid profile in healthy male
      subjects undergoing aerobic training?
AB  - We aimed to investigate the effects of creatine (Cr) supplementation on the
      plasma lipid profile in sedentary male subjects undergoing aerobic training.
      METHODS: Subjects (n = 22) were randomly divided into two groups and were
      allocated to receive treatment with either creatine monohydrate (CR) (~20 g.day-1
      for one week followed by ~10 g.day-1 for a further eleven weeks) or placebo (PL)
      (dextrose) in a double blind fashion. All subjects undertook moderate intensity
      aerobic training during three 40-minute sessions per week, over 3 months. High
      density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL),
      very low-density lipoprotein cholesterol (VLDL), total cholesterol (TC),
      triglyceride (TAG), fasting insulin and fasting glycemia were analyzed in plasma.
      Thereafter, the homeostasis model assessment (HOMA) was calculated. Tests were
      performed at baseline (Pre) and after four (Post 4), eight (Post 8) and twelve
      (Post 12) weeks. RESULTS: We observed main time effects in both groups for HDL
      (Post 4 versus Post 8; P = 0.01), TAG and VLDL (Pre versus Post 4 and Post 8; P =
      0.02 and P = 0.01, respectively). However, no between group differences were
      noted in HDL, LDL, CT, VLDL and TAG. Additionally, fasting insulin, fasting
      glycemia and HOMA did not change significantly. CONCLUSION: These findings
      suggest that Cr supplementation does not exert any additional effect on the
      improvement in the plasma lipid profile than aerobic training alone.

PMID- 18831768
TI  - TOR complex 2 is needed for cell cycle progression and anchorage-independent
      growth of MCF7 and PC3 tumor cells.
AB  - BACKGROUND: AKT signaling promotes cell growth, proliferation and survival and is
      hyperactivated in many cancers. TOR complex 2 (TORC2) activates AKT by
      phosphorylating it on the 'hydrophobic motif' site. Hydrophobic motif site
      phosphorylation is needed only for a subset of AKT functions. Whether
      proliferation of tumor cells depends on TORC2 activity has not been thoroughly
      explored. METHODS: We used RNAi-mediated knockdown of rictor to inhibit TORC2
      activity in MCF7 and PC3 tumor cells to analyze the importance of TORC2 on
      proliferation of tumor cells. RESULTS: TORC2 inhibition reduced proliferation and
      anchorage-independent growth of both cell lines. Rictor depleted cells
      accumulated G1 phase, and showed prominent downregulation of Cyclin D1.
      CONCLUSION: This study provides further evidence that inhibition of TORC2
      activity might be a useful strategy to inhibit proliferation of tumor cells and
      subsequent tumor growth.

PMID- 18831769
TI  - Promoter-sharing by different genes in human genome--CPNE1 and RBM12 gene pair as
      an example.
AB  - BACKGROUND: Regulation of gene expression plays important role in cellular
      functions. Co-regulation of different genes may indicate functional connection or
      even physical interaction between gene products. Thus analysis on genomic
      structures that may affect gene expression regulation could shed light on the
      functions of genes. RESULTS: In a whole genome analysis of alternative splicing
      events, we found that two distinct genes, copine I (CPNE1) and RNA binding motif
      protein 12 (RBM12), share the most 5' exons and therefore the promoter region in
      human. Further analysis identified many gene pairs in human genome that share the
      same promoters and 5' exons but have totally different coding sequences. Analysis
      of genomic and expressed sequences, either cDNAs or expressed sequence tags
      (ESTs) for CPNE1 and RBM12, confirmed the conservation of this phenomenon during
      evolutionary courses. The co-expression of the two genes initiated from the same
      promoter is confirmed by Reverse Transcription-Polymerase Chain Reaction (RT-PCR)
      in different tissues in both human and mouse. High degrees of sequence
      conservation among multiple species in the 5'UTR region common to CPNE1 and RBM12
      were also identified. CONCLUSION: Promoter and 5'UTR sharing between CPNE1 and
      RBM12 is observed in human, mouse and zebrafish. Conservation of this genomic
      structure in evolutionary courses indicates potential functional interaction
      between the two genes. More than 20 other gene pairs in human genome were found
      to have the similar genomic structure in a genome-wide analysis, and it may
      represent a unique pattern of genomic arrangement that may affect expression
      regulation of the corresponding genes.

PMID- 18831770
TI  - Factors influencing psychological distress during a disease epidemic: data from
      Australia's first outbreak of equine influenza.
AB  - BACKGROUND: In 2007 Australia experienced its first outbreak of highly infectious
      equine influenza. Government disease control measures were put in place to
      control, contain, and eradicate the disease; these measures included movement
      restrictions and quarantining of properties. This study was conducted to assess
      the psycho-social impacts of this disease, and this paper reports the prevalence
      of, and factors influencing, psychological distress during this outbreak.
      METHODS: Data were collected using an online survey, with a link directed to the
      affected population via a number of industry groups. Psychological distress, as
      determined by the Kessler 10 Psychological Distress Scale, was the main outcome
      measure. RESULTS: In total, 2760 people participated in this study. Extremely
      high levels of non-specific psychological distress were reported by respondents
      in this study, with 34% reporting high psychological distress (K10 > 22),
      compared to levels of around 12% in the Australian general population. Analysis,
      using backward stepwise binary logistic regression analysis, revealed that those
      living in high risk infection (red) zones (OR = 2.00; 95% CI: 1.57-2.55; p <
      0.001) and disease buffer (amber) zones (OR = 1.83; 95% CI: 1.36-2.46; p < 0.001)
      were at much greater risk of high psychological distress than those living in
      uninfected (white zones). Although prevalence of high psychological distress was
      greater in infected EI zones and States, elevated levels of psychological
      distress were experienced in horse-owners nationally. Statistical analysis
      indicated that certain groups were more vulnerable to high psychological
      distress; specifically younger people, and those with lower levels of formal
      educational qualifications. Respondents whose principal source of income was from
      horse-related industry were more than twice as likely to have high psychological
      distress than those whose primary source of income was not linked to horse
      related industry (OR = 2.23; 95% CI: 1.82-2.73; p < 0.001). CONCLUSION: Although,
      methodologically, this study had good internal validity, it has limited
      generalisability because it was not possible to identify, bound, or sample the
      target population accurately. However, this study is the first to collect
      psychological distress data from an affected population during such a disease
      outbreak and has potential to inform those involved in assessing the potential
      psychological impacts of human infectious diseases, such as pandemic influenza.

PMID- 18831771
TI  - Olfactory function following open rhinoplasty: A 6-month follow-up study.
AB  - BACKGROUND: Patients undergoing any type of nasal surgery may experience degrees
      of postoperative olfactory dysfunction. We sought to investigate "when" the
      olfactory function recovers to its preoperative levels. METHODS: In this cohort
      design, 40 of 65 esthetic open rhinoplasty candidates with equal gender
      distribution, who met the inclusion criteria, were assessed for their olfactory
      function using the Smell Identification Test (SIT) with 40 familiar odors in
      sniffing bottles. All the patients were evaluated for the SIT scores
      preoperatively and postoperatively (at week 1, week 6, and month 6). RESULTS: At
      postoperative week one, 87.5% of the patients had anosmia, and the rest exhibited
      at least moderate levels of hyposmia. The anosmia, which was the dominant pattern
      at postoperative week 1, resolved and converted to various levels of hyposmia, so
      that no one at postoperative week 6 showed any such complain. At postoperative
      week six, 85% of the subjects experienced degrees of hyposmia, almost all being
      mild to moderate. At postoperative six month, the olfactory function had already
      reverted to the preoperative levels: no anosmia or moderate to severe hyposmia. A
      repeated ANOVA was indicative of significant differences in the olfactory
      function at the different time points. According to our post hoc Benfronney, the
      preoperative scores had a significant difference with those at postoperative week
      1, week 6, but not with the ones at month 6. CONCLUSION: Esthetic open
      rhinoplasty may be accompanied by some degrees of postoperative olfactory
      dysfunction. Patients need a time interval of 6 weeks to 6 months to fully
      recover their baseline olfactory function.

PMID- 18831772
TI  - Risk factors associated with non-alcoholic fatty liver disease in subjects from
      primary care units. A case-control study.
AB  - BACKGROUND: Non alcoholic fatty liver disease (NAFL) consists in the accumulation
      of fat vacuoles in the cytoplasm of hepatocytes. Many etiologic factors are
      associated with NAFL, such as, the metabolic syndrome factors, medications,
      bariatric surgery, nutritional disorders. However, very little information is
      available on the clinical relevance of this disorder as a health problem in the
      general population. METHODS AND DESIGN: The aim of the study is establish the
      risk factors most frequently associated with NAFL in a general adult population
      assigned to the primary care units and to investigate the relationship between
      each component of the metabolic syndrome and the risk of having a NAFL. A
      population based case-control, observational and multicenter study will be
      carried out in 18 primary care units from the "Area de Gestion del Barcelones
      Nord y Maresme" (Barcelona) attending a population of 360,000 inhabitants and
      will include 326 cases and 370 controls. Cases are defined as all subjects
      fulfilling the inclusion criteria and with evidence of fatty liver in an
      abdominal ultrasonography performed for any reason. One control will be randomly
      selected for each case from the population, matched for age, gender and primary
      care center. Controls with fatty liver or other liver diseases will be excluded.
      All cases and controls will be asked about previous hepatic diseases, consumption
      of alcohol, smoking and drugs, and a physical examination, biochemical analyses
      including liver function tests, the different components of the metabolic
      syndrome and the HAIR score will also be performed. Paired controls will also
      undergo an abdominal ultrasonography. DISCUSSION: This study will attempt to
      determine the factors most frequently associated with the presence of NAFL
      investigate the relationship between the metabolic syndrome and the risk of fatty
      liver and study the influence of the different primary care professionals in
      avoiding the evolution of the disease.

PMID- 18831773
TI  - Genomics, molecular imaging, bioinformatics, and bio-nano-info integration are
      synergistic components of translational medicine and personalized healthcare
      research.
AB  - Supported by National Science Foundation (NSF), International Society of
      Intelligent Biological Medicine (ISIBM), International Journal of Computational
      Biology and Drug Design and International Journal of Functional Informatics and
      Personalized Medicine, IEEE 7th Bioinformatics and Bioengineering attracted more
      than 600 papers and 500 researchers and medical doctors. It was the only
      synergistic inter/multidisciplinary IEEE conference with 24 Keynote Lectures, 7
      Tutorials, 5 Cutting-Edge Research Workshops and 32 Scientific Sessions including
      11 Special Research Interest Sessions that were designed dynamically at Harvard
      in response to the current research trends and advances. The committee was very
      grateful for the IEEE Plenary Keynote Lectures given by: Dr. A. Keith Dunker
      (Indiana), Dr. Jun Liu (Harvard), Dr. Brian Athey (Michigan), Dr. Mark Borodovsky
      (Georgia Tech and President of ISIBM), Dr. Hamid Arabnia (Georgia and Vice
      President of ISIBM), Dr. Ruzena Bajcsy (Berkeley and Member of United States
      National Academy of Engineering and Member of United States Institute of Medicine
      of the National Academies), Dr. Mary Yang (United States National Institutes of
      Health and Oak Ridge, DOE), Dr. Chih-Ming Ho (UCLA and Member of United States
      National Academy of Engineering and Academician of Academia Sinica), Dr. Andy
      Baxevanis (United States National Institutes of Health), Dr. Arif Ghafoor
      (Purdue), Dr. John Quackenbush (Harvard), Dr. Eric Jakobsson (UIUC), Dr. Vladimir
      Uversky (Indiana), Dr. Laura Elnitski (United States National Institutes of
      Health) and other world-class scientific leaders. The Harvard meeting was a large
      academic event 100% full-sponsored by IEEE financially and academically. After a
      rigorous peer-review process, the committee selected 27 high-quality research
      papers from 600 submissions. The committee is grateful for contributions from
      keynote speakers Dr. Russ Altman (IEEE BIBM conference keynote lecturer on
      combining simulation and machine learning to recognize function in 4D), Dr. Mary
      Qu Yang (IEEE BIBM workshop keynote lecturer on new initiatives of detecting
      microscopic disease using machine learning and molecular biology,
      http://ieeexplore.ieee.org/servlet/opac?punumber=4425386) and Dr. Jack Y. Yang
      (IEEE BIBM workshop keynote lecturer on data mining and knowledge discovery in
      translational medicine) from the first IEEE Computer Society BioInformatics and
      BioMedicine (IEEE BIBM) international conference and workshops, November 2-4,
      2007, Silicon Valley, California, USA.

PMID- 18831775
TI  - Batch Blast Extractor: an automated blastx parser application.
AB  - MOTIVATION: BLAST programs are very efficient in finding similarities for
      sequences. However for large datasets such as ESTs, manual extraction of the
      information from the batch BLAST output is needed. This can be time consuming,
      insufficient, and inaccurate. Therefore implementation of a parser application
      would be extremely useful in extracting information from BLAST outputs. RESULTS:
      We have developed a java application, Batch Blast Extractor, with a user friendly
      graphical interface to extract information from BLAST output. The application
      generates a tab delimited text file that can be easily imported into any
      statistical package such as Excel or SPSS for further analysis. For each BLAST
      hit, the program obtains and saves the essential features from the BLAST output
      file that would allow further analysis. The program was written in Java and
      therefore is OS independent. It works on both Windows and Linux OS with java 1.4
      and higher. It is freely available from: http://mcbc.usm.edu/BatchBlastExtractor/

PMID- 18831774
TI  - The unfoldomics decade: an update on intrinsically disordered proteins.
AB  - BACKGROUND: Our first predictor of protein disorder was published just over a
      decade ago in the Proceedings of the IEEE International Conference on Neural
      Networks (Romero P, Obradovic Z, Kissinger C, Villafranca JE, Dunker AK (1997)
      Identifying disordered regions in proteins from amino acid sequence. Proceedings
      of the IEEE International Conference on Neural Networks, 1: 90-95). By now more
      than twenty other laboratory groups have joined the efforts to improve the
      prediction of protein disorder. While the various prediction methodologies used
      for protein intrinsic disorder resemble those methodologies used for secondary
      structure prediction, the two types of structures are entirely different. For
      example, the two structural classes have very different dynamic properties, with
      the irregular secondary structure class being much less mobile than the disorder
      class. The prediction of secondary structure has been useful. On the other hand,
      the prediction of intrinsic disorder has been revolutionary, leading to major
      modifications of the more than 100 year-old views relating protein structure and
      function. Experimentalists have been providing evidence over many decades that
      some proteins lack fixed structure or are disordered (or unfolded) under
      physiological conditions. In addition, experimentalists are also showing that,
      for many proteins, their functions depend on the unstructured rather than
      structured state; such results are in marked contrast to the greater than hundred
      year old views such as the lock and key hypothesis. Despite extensive data on
      many important examples, including disease-associated proteins, the importance of
      disorder for protein function has been largely ignored. Indeed, to our knowledge,
      current biochemistry books don't present even one acknowledged example of a
      disorder-dependent function, even though some reports of disorder-dependent
      functions are more than 50 years old. The results from genome-wide predictions of
      intrinsic disorder and the results from other bioinformatics studies of intrinsic
      disorder are demanding attention for these proteins. RESULTS: Disorder prediction
      has been important for showing that the relatively few experimentally
      characterized examples are members of a very large collection of related
      disordered proteins that are wide-spread over all three domains of life. Many
      significant biological functions are now known to depend directly on, or are
      importantly associated with, the unfolded or partially folded state. Here our
      goal is to review the key discoveries and to weave these discoveries together to
      support novel approaches for understanding sequence-function relationships.
      CONCLUSION: Intrinsically disordered protein is common across the three domains
      of life, but especially common among the eukaryotic proteomes. Signaling
      sequences and sites of posttranslational modifications are frequently, or very
      likely most often, located within regions of intrinsic disorder. Disorder-to
      order transitions are coupled with the adoption of different structures with
      different partners. Also, the flexibility of intrinsic disorder helps different
      disordered regions to bind to a common binding site on a common partner. Such
      capacity for binding diversity plays important roles in both protein-protein
      interaction networks and likely also in gene regulation networks. Such disorder
      based signaling is further modulated in multicellular eukaryotes by alternative
      splicing, for which such splicing events map to regions of disorder much more
      often than to regions of structure. Associating alternative splicing with
      disorder rather than structure alleviates theoretical and experimentally observed
      problems associated with the folding of different length, isomeric amino acid
      sequences. The combination of disorder and alternative splicing is proposed to
      provide a mechanism for easily "trying out" different signaling pathways, thereby
      providing the mechanism for generating signaling diversity and enabling the
      evolution of cell differentiation and multicellularity. Finally, several recent
      small molecules of interest as potential drugs have been shown to act by blocking
      protein-protein interactions based on intrinsic disorder of one of the partners.
      Study of these examples has led to a new approach for drug discovery, and
      bioinformatics analysis of the human proteome suggests that various disease
      associated proteins are very rich in such disorder-based drug discovery targets.

PMID- 18831776
TI  - ILOOP--a web application for two-channel microarray interwoven loop design.
AB  - Microarray technology is widely applied to address complex scientific questions.
      However, there remain fundamental issues on how to design experiments to ensure
      that the resulting data enables robust statistical analysis. Interwoven loop
      design has several advantages over other designs. However it suffers in the
      complexity of design. We have implemented an online web application which allows
      users to find optimal loop designs for two-color microarray experiments. Given a
      number of conditions (such as treatments or time points) and replicates, the
      application will find the best possible design of the experiment and output
      experimental parameters. It is freely available from http://mcbc.usm.edu/iloop.

PMID- 18831777
TI  - Approaches to reduce false positives and false negatives in the analysis of
      microarray data: applications in type 1 diabetes research.
AB  - BACKGROUND: As studies of molecular biology system attempt to achieve a
      comprehensive understanding of a particular system, Type 1 errors may be a
      significant problem. However, few investigators are inclined to accept the
      increase in Type 2 errors (false positives) that may result when less stringent
      statistical cut-off values are used. To address this dilemma, we developed an
      analysis strategy that used a stringent statistical analysis to create a list of
      differentially expressed genes that served as "bait" to "fish out" other genes
      with similar patterns of expression. RESULTS: Comparing two strains of mice (NOD
      and C57Bl/6), we identified 93 genes with statistically significant differences
      in their patterns of expression. Hierarchical clustering identified an additional
      39 genes with similar patterns of expression differences between the two strains.
      Pathway analysis was then employed: 1) identify the central genes and define
      biological processes that may be regulated by the genes identified, and 2)
      identify genes on the lists that could not be connected to each other in pathways
      (potential false positives). For networks created by both gene lists, the most
      connected (central) genes were interferon gamma (IFN-gamma) and tumor necrosis
      factor alpha (TNF-alpha). These two cytokines are relevant to the biological
      differences between the two strains of mice. Furthermore, the network created by
      the list of 39 genes also suggested other biological differences between the
      strains. CONCLUSION: Taken together, these data demonstrate how stringent
      statistical analysis, combined with hierarchical clustering and pathway analysis
      may offer deeper insight into the biological processes reflected from a set of
      expression array data. This approach allows us to 'recapture" false negative
      genes that otherwise would have been missed by the statistical analysis.

PMID- 18831778
TI  - Improving the specificity of exon prediction using comparative genomics.
AB  - BACKGROUND: Computational gene prediction tools routinely generate large volumes
      of predicted coding exons (putative exons). One common limitation of these tools
      is the relatively low specificity due to the large amount of non-coding regions.
      METHODS: A statistical approach is developed that largely improves the gene
      prediction specificity. The key idea is to utilize the evolutionary conservation
      principle relative to the coding exons. By first exploiting the homology between
      genomes of two related species, a probability model for the evolutionary
      conservation pattern of codons across different genomes is developed. A
      probability model for the dependency between adjacent codons/triplets is added to
      differentiate coding exons and random sequences. Finally, the log odds ratio is
      developed to classify putative exons into the group of coding exons and the group
      of non-coding regions. RESULTS: The method was tested on pre-aligned human-mouse
      sequences where the putative exons are predicted by GENSCAN and TWINSCAN. The
      proposed method is able to improve the exon specificity by 73% and 32%
      respectively, while the loss of the sensitivity < or = 1%. The method also keeps
      98% of RefSeq gene structures that are correctly predicted by TWINSCAN when
      removing 26% of predicted genes that are in non-coding regions. The estimated
      number of true exons in TWINSCAN's predictions is 157,070. The results and the
      executable codes can be downloaded from http://www.stat.purdue.edu/~jingwu/codon/
      CONCLUSION: The proposed method demonstrates an application of the evolutionary
      conservation principle to coding exons. It is a complementary method which can be
      used as an additional criteria to refine many existing gene predictions.

PMID- 18831779
TI  - Selecting informative genes for discriminant analysis using multigene expression
      profiles.
AB  - BACKGROUND: Gene expression data extracted from microarray experiments have been
      used to study the difference between mRNA abundance of genes under different
      conditions. In one of such experiments, thousands of genes are measured
      simultaneously, which provides a high-dimensional feature space for
      discriminating between different sample classes. However, most of these
      dimensions are not informative about the between-class difference, and add noises
      to the discriminant analysis. RESULTS: In this paper we propose and study feature
      selection methods that evaluate the "informativeness" of a set of genes. Two
      measures of information based on multigene expression profiles are considered for
      a backward information-driven screening approach for selecting important gene
      features. By considering multigene expression profiles, we are able to utilize
      interaction information among these genes. Using a breast cancer data, we
      illustrate our methods and compare them to the performance of existing methods.
      CONCLUSION: We illustrate in this paper that methods considering gene-gene
      interactions have better classification power in gene expression analysis. In our
      results, we identify important genes with relative large p-values from single
      gene tests. This indicates that these are genes with weak marginal information
      but strong interaction information, which will be overlooked by strategies that
      only examine individual genes.

PMID- 18831780
TI  - Phylogenetic reconstruction from transpositions.
AB  - BACKGROUND: Because of the advent of high-throughput sequencing and the
      consequent reduction in the cost of sequencing, many organisms have been
      completely sequenced and most of their genes identified. It thus has become
      possible to represent whole genomes as ordered lists of gene identifiers and to
      study the rearrangement of these entities through computational means. As a
      result, genome rearrangement data has attracted increasing attentions from both
      biologists and computer scientists as a new type of data for phylogenetic
      analysis. The main events of genome rearrangements include inversions,
      transpositions and transversions. To date, GRAPPA and MGR are the most accurate
      methods for rearrangement phylogeny, both assuming inversion as the only event.
      However, due to the complexity of computing transposition distance, it is very
      difficult to analyze datasets when transpositions are dominant. RESULTS: We
      extend GRAPPA to handle transpositions. The new method is named GRAPPA-TP, with
      two major extensions: a heuristic method to estimate transposition distance, and
      a new transposition median solver for three genomes. Although GRAPPA-TP uses a
      greedy approach to compute the transposition distance, it is very accurate when
      genomes are relatively close. The new GRAPPA-TP is available from
      http://phylo.cse.sc.edu/. CONCLUSION: Our extensive testing using simulated
      datasets shows that GRAPPA-TP is very accurate in terms of ancestor genome
      inference and phylogenetic reconstruction. Simulation results also suggest that
      model match is critical in genome rearrangement analysis: it is not accurate to
      simulate transpositions with other events including inversions.

PMID- 18831781
TI  - Use artificial neural network to align biological ontologies.
AB  - BACKGROUND: Being formal, declarative knowledge representation models, ontologies
      help to address the problem of imprecise terminologies in biological and
      biomedical research. However, ontologies constructed under the auspices of the
      Open Biomedical Ontologies (OBO) group have exhibited a great deal of variety,
      because different parties can design ontologies according to their own conceptual
      views of the world. It is therefore becoming critical to align ontologies from
      different parties. During automated/semi-automated alignment across biological
      ontologies, different semantic aspects, i.e., concept name, concept properties,
      and concept relationships, contribute in different degrees to alignment results.
      Therefore, a vector of weights must be assigned to these semantic aspects. It is
      not trivial to determine what those weights should be, and current methodologies
      depend a lot on human heuristics. RESULTS: In this paper, we take an artificial
      neural network approach to learn and adjust these weights, and thereby support a
      new ontology alignment algorithm, customized for biological ontologies, with the
      purpose of avoiding some disadvantages in both rule-based and learning-based
      aligning algorithms. This approach has been evaluated by aligning two real-world
      biological ontologies, whose features include huge file size, very few instances,
      concept names in numerical strings, and others. CONCLUSION: The promising
      experiment results verify our proposed hypothesis, i.e., three weights for
      semantic aspects learned from a subset of concepts are representative of all
      concepts in the same ontology. Therefore, our method represents a large leap
      forward towards automating biological ontology alignment.

PMID- 18831782
TI  - Array CGH data modeling and smoothing in Stationary Wavelet Packet Transform
      domain.
AB  - BACKGROUND: Array-based comparative genomic hybridization (array CGH) is a highly
      efficient technique, allowing the simultaneous measurement of genomic DNA copy
      number at hundreds or thousands of loci and the reliable detection of local one
      copy-level variations. Characterization of these DNA copy number changes is
      important for both the basic understanding of cancer and its diagnosis. In order
      to develop effective methods to identify aberration regions from array CGH data,
      many recent research work focus on both smoothing-based and segmentation-based
      data processing. In this paper, we propose stationary packet wavelet transform
      based approach to smooth array CGH data. Our purpose is to remove CGH noise in
      whole frequency while keeping true signal by using bivariate model. RESULTS: In
      both synthetic and real CGH data, Stationary Wavelet Packet Transform (SWPT) is
      the best wavelet transform to analyze CGH signal in whole frequency. We also
      introduce a new bivariate shrinkage model which shows the relationship of CGH
      noisy coefficients of two scales in SWPT. Before smoothing, the symmetric
      extension is considered as a preprocessing step to save information at the
      border. CONCLUSION: We have designed the SWTP and the SWPT-Bi which are using the
      stationary wavelet packet transform with the hard thresholding and the new
      bivariate shrinkage estimator respectively to smooth the array CGH data. We
      demonstrate the effectiveness of our approach through theoretical and
      experimental exploration of a set of array CGH data, including both synthetic
      data and real data. The comparison results show that our method outperforms the
      previous approaches.

PMID- 18831783
TI  - A stable iterative method for refining discriminative gene clusters.
AB  - BACKGROUND: Microarray technology is often used to identify the genes that are
      differentially expressed between two biological conditions. On the other hand,
      since microarray datasets contain a small number of samples and a large number of
      genes, it is usually desirable to identify small gene subsets with distinct
      pattern between sample classes. Such gene subsets are highly discriminative in
      phenotype classification because of their tightly coupling features.
      Unfortunately, such identified classifiers usually tend to have poor
      generalization properties on the test samples due to overfitting problem.
      RESULTS: We propose a novel approach combining both supervised learning with
      unsupervised learning techniques to generate increasingly discriminative gene
      clusters in an iterative manner. Our experiments on both simulated and real
      datasets show that our method can produce a series of robust gene clusters with
      good classification performance compared with existing approaches. CONCLUSION:
      This backward approach for refining a series of highly discriminative gene
      clusters for classification purpose proves to be very consistent and stable when
      applied to various types of training samples.

PMID- 18831784
TI  - Inferring gene regulatory networks by thermodynamic modeling.
AB  - BACKGROUND: To date, the reconstruction of gene regulatory networks from gene
      expression data has primarily relied on the correlation between the expression of
      transcription regulators and that of target genes. RESULTS: We developed a
      network reconstruction method based on quantities that are closely related to the
      biophysical properties of TF-TF interaction, TF-DNA binding and transcriptional
      activation and repression. The Network-Identifier method utilized a thermodynamic
      model for gene regulation to infer regulatory relationships from multiple time
      course gene expression datasets. Applied to five datasets of differentiating
      embryonic stem cells, Network-Identifier identified a gene regulatory network
      among 87 transcription regulator genes. This network suggests that Oct4, Sox2 and
      Klf4 indirectly repress lineage specific differentiation genes by activating
      transcriptional repressors of Ctbp2, Rest and Mtf2.

PMID- 18831785
TI  - The FEATURE framework for protein function annotation: modeling new functions,
      improving performance, and extending to novel applications.
AB  - Structural genomics efforts contribute new protein structures that often lack
      significant sequence and fold similarity to known proteins. Traditional sequence
      and structure-based methods may not be sufficient to annotate the molecular
      functions of these structures. Techniques that combine structural and functional
      modeling can be valuable for functional annotation. FEATURE is a flexible
      framework for modeling and recognition of functional sites in macromolecular
      structures. Here, we present an overview of the main components of the FEATURE
      framework, and describe the recent developments in its use. These include
      automating training sets selection to increase functional coverage, coupling
      FEATURE to structural diversity generating methods such as molecular dynamics
      simulations and loop modeling methods to improve performance, and using FEATURE
      in large-scale modeling and structure determination efforts.

PMID- 18831786
TI  - Extending bicluster analysis to annotate unclassified ORFs and predict novel
      functional modules using expression data.
AB  - BACKGROUND: Microarrays have the capacity to measure the expressions of thousands
      of genes in parallel over many experimental samples. The unsupervised
      classification technique of bicluster analysis has been employed previously to
      uncover gene expression correlations over subsets of samples with the aim of
      providing a more accurate model of the natural gene functional classes. This
      approach also has the potential to aid functional annotation of unclassified open
      reading frames (ORFs). Until now this aspect of biclustering has been under
      explored. In this work we illustrate how bicluster analysis may be extended into
      a 'semi-supervised' ORF annotation approach referred to as BALBOA. RESULTS: The
      efficacy of the BALBOA ORF classification technique is first assessed via cross
      validation and compared to a multi-class k-Nearest Neighbour (kNN) benchmark
      across three independent gene expression datasets. BALBOA is then used to assign
      putative functional annotations to unclassified yeast ORFs. These predictions are
      evaluated using existing experimental and protein sequence information. Lastly,
      we employ a related semi-supervised method to predict the presence of novel
      functional modules within yeast. CONCLUSION: In this paper we demonstrate how
      unsupervised classification methods, such as bicluster analysis, may be extended
      using of available annotations to form semi-supervised approaches within the gene
      expression analysis domain. We show that such methods have the potential to
      improve upon supervised approaches and shed new light on the functions of
      unclassified ORFs and their co-regulation.

PMID- 18831787
TI  - Tumor classification ranking from microarray data.
AB  - BACKGROUND: Gene expression profiles based on microarray data are recognized as
      potential diagnostic indices of cancer. Molecular tumor classifications resulted
      from these data and learning algorithms have advanced our understanding of
      genetic changes associated with cancer etiology and development. However,
      classifications are not always perfect and in such cases the classification
      rankings (likelihoods of correct class predictions) can be useful for directing
      further research (e.g., by deriving inferences about predictive indicators or
      prioritizing future experiments). Classification ranking is a challenging
      problem, particularly for microarray data, where there is a huge number of
      possible regulated genes with no known rating function. This study investigates
      the possibility of making tumor classification more informative by using a method
      for classification ranking that requires no additional ranking analysis and
      maintains relatively good classification accuracy. RESULTS: Microarray data of 11
      different types and subtypes of cancer were analyzed using MDR (Multi-Dimensional
      Ranker), a recently developed boosting-based ranking algorithm. The number of
      predictor genes in all of the resulting classification models was at most nine, a
      huge reduction from the more than 12 thousands genes in the majority of the
      expression samples. Compared to several other learning algorithms, MDR gives the
      greatest AUC (area under the ROC curve) for the classifications of prostate
      cancer, acute lymphoblastic leukemia (ALL) and four ALL subtypes: BCR-ABL, E2A
      PBX1, MALL and TALL. SVM (Support Vector Machine) gives the highest AUC for the
      classifications of lung, lymphoma, and breast cancers, and two ALL subtypes:
      Hyperdiploid > 50 and TEL-AML1. MDR gives highly competitive results, producing
      the highest average AUC, 91.01%, and an average overall accuracy of 90.01% for
      cancer expression analysis. CONCLUSION: Using the classification rankings from
      MDR is a simple technique for obtaining effective and informative tumor
      classifications from cancer gene expression data. Further interpretation of the
      results obtained from MDR is required. MDR can also be used directly as a simple
      feature selection mechanism to identify genes relevant to tumor classification.
      MDR may be applicable to many other classification problems for microarray data.

PMID- 18831788
TI  - Transcription factor and microRNA regulation in androgen-dependent and 
      independent prostate cancer cells.
AB  - BACKGROUND: Prostate cancer is one of the leading causes of cancer death in men.
      Androgen ablation, the most commonly-used therapy for progressive prostate
      cancer, is ineffective once the cancer cells become androgen-independent. The
      regulatory mechanisms that cause this transition (from androgen-dependent to
      androgen-independent) remain unknown. In this study, based on the microarray data
      comparing global gene expression patterns in the prostate tissue between androgen
      dependent and -independent prostate cancer patients, we identify a set of
      transcription factors and microRNAs that potentially cause such difference, using
      a model-based computational approach. RESULTS: From 335 position weight matrices
      in the TRANSFAC database and 564 microRNAs in the microRNA registry, our model
      identify 5 transcription factors and 7 microRNAs to be potentially responsible
      for the level of androgen dependency. Of these transcription factors and
      microRNAs, the estimated function of all the 5 transcription factors are
      predicted to be inhibiting transcription in androgen-independent samples
      comparing with the dependent ones. Six out of 7 microRNAs, however, demonstrated
      stimulatory effects. We also find that the expression levels of three predicted
      transcription factors, including AP-1, STAT3 (signal transducers and activators
      of transcription 3), and DBP (albumin D-box) are significantly different between
      androgen-dependent and -independent patients. In addition, microRNA microarray
      data from other studies confirm that several predicted microRNAs, including miR
      21, miR-135a, and miR-135b, demonstrate differential expression in prostate
      cancer cells, comparing with normal tissues. CONCLUSION: We present a model-based
      computational approach to identify transcription factors and microRNAs
      influencing the progression of androgen-dependent prostate cancer to androgen
      independent prostate cancer. This result suggests that the capability of
      transcription factors to initiate transcription and microRNAs to facilitate mRNA
      degradation are both decreased in androgen-independent prostate cancer. The
      proposed model-based approach indicates that considering combinatorial effects of
      transcription factors and microRNAs in a unified model provides additional
      transcriptional and post-transcriptional regulatory mechanisms on global gene
      expression in the prostate cancer with different hormone-dependency.

PMID- 18831789
TI  - A Poisson mixture model to identify changes in RNA polymerase II binding quantity
      using high-throughput sequencing technology.
AB  - We present a mixture model-based analysis for identifying differences in the
      distribution of RNA polymerase II (Pol II) in transcribed regions, measured using
      ChIP-seq (chromatin immunoprecipitation following massively parallel sequencing
      technology). The statistical model assumes that the number of Pol II-targeted
      sequences contained within each genomic region follows a Poisson distribution. A
      Poisson mixture model was then developed to distinguish Pol II binding changes in
      transcribed region using an empirical approach and an expectation-maximization
      (EM) algorithm developed for estimation and inference. In order to achieve a
      global maximum in the M-step, a particle swarm optimization (PSO) was
      implemented. We applied this model to Pol II binding data generated from hormone
      dependent MCF7 breast cancer cells and antiestrogen-resistant MCF7 breast cancer
      cells before and after treatment with 17beta-estradiol (E2). We determined that
      in the hormone-dependent cells, approximately 9.9% (2527) genes showed
      significant changes in Pol II binding after E2 treatment. However, only
      approximately 0.7% (172) genes displayed significant Pol II binding changes in E2
      treated antiestrogen-resistant cells. These results show that a Poisson mixture
      model can be used to analyze ChIP-seq data.

PMID- 18831790
TI  - Selecting subsets of newly extracted features from PCA and PLS in microarray data
      analysis.
AB  - BACKGROUND: Dimension reduction is a critical issue in the analysis of microarray
      data, because the high dimensionality of gene expression microarray data set
      hurts generalization performance of classifiers. It consists of two types of
      methods, i.e. feature selection and feature extraction. Principle component
      analysis (PCA) and partial least squares (PLS) are two frequently used feature
      extraction methods, and in the previous works, the top several components of PCA
      or PLS are selected for modeling according to the descending order of
      eigenvalues. While in this paper, we prove that not all the top features are
      useful, but features should be selected from all the components by feature
      selection methods. RESULTS: We demonstrate a framework for selecting feature
      subsets from all the newly extracted components, leading to reduced
      classification error rates on the gene expression microarray data. Here we have
      considered both an unsupervised method PCA and a supervised method PLS for
      extracting new components, genetic algorithms for feature selection, and support
      vector machines and k nearest neighbor for classification. Experimental results
      illustrate that our proposed framework is effective to select feature subsets and
      to reduce classification error rates. CONCLUSION: Not only the top features newly
      extracted by PCA or PLS are important, therefore, feature selection should be
      performed to select subsets from new features to improve generalization
      performance of classifiers.

PMID- 18831791
TI  - MeDor: a metaserver for predicting protein disorder.
AB  - BACKGROUND: We have previously shown that using multiple prediction methods
      improves the accuracy of disorder predictions. It is, however, a time-consuming
      procedure, since individual outputs of multiple predictions have to be retrieved,
      compared to each other and a comprehensive view of the results can only be
      obtained through a manual, fastidious, non-automated procedure. We herein
      describe a new web metaserver, MeDor, which allows fast, simultaneous analysis of
      a query sequence by multiple predictors and provides a graphical interface with a
      unified view of the outputs. RESULTS: MeDor was developed in Java and is freely
      available and downloadable at: http://www.vazymolo.org/MeDor/index.html.
      Presently, MeDor provides a HCA plot and runs a secondary structure prediction, a
      prediction of signal peptides and transmembrane regions and a set of disorder
      predictions. MeDor also enables the user to customize the output and to retrieve
      the sequence of specific regions of interest. CONCLUSION: As MeDor outputs can be
      printed, saved, commented and modified further on, this offers a dynamic support
      for the analysis of protein sequences that is instrumental for delineating
      domains amenable to structural and functional studies.

PMID- 18831792
TI  - Short Linear Motifs recognized by SH2, SH3 and Ser/Thr Kinase domains are
      conserved in disordered protein regions.
AB  - BACKGROUND: Protein interactions are essential for most cellular functions.
      Interactions mediated by domains that appear in a large number of proteins are of
      particular interest since they are expected to have an impact on diversities of
      cellular processes such as signal transduction and immune response. Many well
      represented domains recognize and bind to primary sequences less than 10 amino
      acids in length called Short Linear Motifs (SLiMs). RESULTS: In this study, we
      systematically studied the evolutionary conservation of SLiMs recognized by SH2,
      SH3 and Ser/Thr Kinase domains in both ordered and disordered protein regions.
      Disordered protein regions are protein sequences that lack a fixed three
      dimensional structure under putatively native conditions. We find that, in all
      these domains examined, SLiMs are more conserved in disordered regions. This
      trend is more evident in those protein functional groups that are frequently
      reported to interact with specific domains. CONCLUSION: The correlation between
      SLiM conservation with disorder prediction demonstrates that functional SLiMs
      recognized by each domain occur more often in disordered as compared to
      structured regions of proteins.

PMID- 18831793
TI  - Gene selection algorithm by combining reliefF and mRMR.
AB  - BACKGROUND: Gene expression data usually contains a large number of genes, but a
      small number of samples. Feature selection for gene expression data aims at
      finding a set of genes that best discriminate biological samples of different
      types. In this paper, we present a two-stage selection algorithm by combining
      ReliefF and mRMR: In the first stage, ReliefF is applied to find a candidate gene
      set; In the second stage, mRMR method is applied to directly and explicitly
      reduce redundancy for selecting a compact yet effective gene subset from the
      candidate set. RESULTS: We perform comprehensive experiments to compare the mRMR
      ReliefF selection algorithm with ReliefF, mRMR and other feature selection
      methods using two classifiers as SVM and Naive Bayes, on seven different
      datasets. And we also provide all source codes and datasets for sharing with
      others. CONCLUSION: The experimental results show that the mRMR-ReliefF gene
      selection algorithm is very effective.

PMID- 18831794
TI  - Diversity of core promoter elements comprising human bidirectional promoters.
AB  - BACKGROUND: Bidirectional promoters lie between adjacent genes, which are
      transcribed from opposite strands of DNA. The functional mechanisms underlying
      the activation of bidirectional promoters are currently uncharacterised. To
      define the core promoter elements of bidirectional promoters in human, we mapped
      motifs for TATA, INR, BRE, DPE, INR, as well as CpG-islands. RESULTS: We found a
      consistently high correspondence between C+G content, CpG-island presence and an
      average expression level increasing the median level for all genes in
      bidirectional promoters. These CpG-rich promoters showed discrete initiation
      patterns rather than broad regions of transcription initiation, as are typically
      seen for CpG-island promoters. CpG-islands encompass both TSSs within
      bidirectional promoters, providing an explanation for the symmetrical co
      expression patterns of many of these genes. In contrast, TATA motifs appear to be
      asymmetrically positioned at one TSS or the other. CONCLUSION: Our findings
      demonstrate that bidirectional promoters utilize a variety of core promoter
      elements to initiate transcription. CpG-islands dominate the regulatory landscape
      of this group of promoters.

PMID- 18831795
TI  - Protein intrinsic disorder toolbox for comparative analysis of viral proteins.
AB  - To examine the usefulness of protein disorder predictions as a tool for the
      comparative analysis of viral proteins, a relational database has been
      constructed. The database includes proteins from influenza A and HIV-related
      viruses. Annotations include viral protein sequence, disorder prediction,
      structure, and function. Location of each protein within a virion, if known, is
      also denoted. Our analysis reveals a clear relationship between proximity to the
      RNA core and the percentage of predicted disordered residues for a set of
      influenza A virus proteins. Neuraminidases (NA) and hemagglutinin (HA) of major
      influenza A pandemics tend to pair in such a way that both proteins tend to be
      either ordered-ordered or disordered-disordered by prediction. This may be the
      result of these proteins evolving from being lipid-associated. High abundance of
      intrinsic disorder in envelope and matrix proteins from HIV-related viruses
      likely represents a mechanism where HIV virions can escape immune response
      despite the availability of antibodies for the HIV-related proteins. This
      exercise provides an example showing how the combined use of intrinsic disorder
      predictions and relational databases provides an improved understanding of the
      functional and structural behaviour of viral proteins.

PMID- 18831796
TI  - Assessment of data processing to improve reliability of microarray experiments
      using genomic DNA reference.
AB  - BACKGROUND: Using genomic DNA as common reference in microarray experiments has
      recently been tested by different laboratories. Conflicting results have been
      reported with regard to the reliability of microarray results using this method.
      To explain it, we hypothesize that data processing is a critical element that
      impacts the data quality. RESULTS: Microarray experiments were performed in a
      gamma-proteobacterium Shewanella oneidensis. Pair-wise comparison of three
      experimental conditions was obtained either with two labeled cDNA samples co
      hybridized to the same array, or by employing Shewanella genomic DNA as a
      standard reference. Various data processing techniques were exploited to reduce
      the amount of inconsistency between both methods and the results were assessed.
      We discovered that data quality was significantly improved by imposing the
      constraint of minimal number of replicates, logarithmic transformation and random
      error analyses. CONCLUSION: These findings demonstrate that data processing
      significantly influences data quality, which provides an explanation for the
      conflicting evaluation in the literature. This work could serve as a guideline
      for microarray data analysis using genomic DNA as a standard reference.

PMID- 18831797
TI  - In silico comparison of transcript abundances during Arabidopsis thaliana and
      Glycine max resistance to Fusarium virguliforme.
AB  - BACKGROUND: Sudden death syndrome (SDS) of soybean (Glycine max L. Merr.) is an
      economically important disease, caused by the semi-biotrophic fungus Fusarium
      solani f. sp. glycines, recently renamed Fusarium virguliforme (Fv). Due to the
      complexity and length of the soybean-Fusarium interaction, the molecular
      mechanisms underlying plant resistance and susceptibility to the pathogen are not
      fully understood. F. virguliforme has a very wide host range for the ability to
      cause root rot and a very narrow host range for the ability to cause a leaf
      scorch. Arabidopsis thaliana is a host for many types of phytopathogens including
      bacteria, fungi, viruses and nematodes. Deciphering the variations among
      transcript abundances (TAs) of functional orthologous genes of soybean and A.
      thaliana involved in the interaction will provide insights into plant resistance
      to F. viguliforme. RESULTS: In this study, we reported the analyses of
      microarrays measuring TA in whole plants after A. thaliana cv 'Columbia' was
      challenged with fungal pathogen F. virguliforme. Infection caused significant
      variations in TAs. The total number of increased transcripts was nearly four
      times more than that of decreased transcripts in abundance. A putative resistance
      pathway involved in responding to the pathogen infection in A. thaliana was
      identified and compared to that reported in soybean. CONCLUSION: Microarray
      experiments allow the interrogation of tens of thousands of transcripts
      simultaneously and thus, the identification of plant pathways is likely to be
      involved in plant resistance to Fusarial pathogens. Dissection of the set
      functional orthologous genes between soybean and A. thaliana enabled a broad view
      of the functional relationships and molecular interactions among plant genes
      involved in F. virguliforme resistance.

PMID- 18831798
TI  - Biomarker discovery across annotated and unannotated microarray datasets using
      semi-supervised learning.
AB  - The growing body of DNA microarray data has the potential to advance our
      understanding of the molecular basis of disease. However annotating microarray
      datasets with clinically useful information is not always possible, as this often
      requires access to detailed patient records. In this study we introduce GLAD, a
      new Semi-Supervised Learning (SSL) method for combining independent annotated
      datasets and unannotated datasets with the aim of identifying more robust sample
      classifiers. In our method, independent models are developed using subsets of
      genes for the annotated and unannotated datasets. These models are evaluated
      according to a scoring function that incorporates terms for classification
      accuracy on annotated data, and relative cluster separation in unannotated data.
      Improved models are iteratively generated using a genetic algorithm feature
      selection technique. Our results show that the addition of unannotated data into
      training, significantly improves classifier robustness.

PMID- 18831799
TI  - Predicting protein disorder by analyzing amino acid sequence.
AB  - BACKGROUND: Many protein regions and some entire proteins have no definite
      tertiary structure, presenting instead as dynamic, disorder ensembles under
      different physiochemical circumstances. These proteins and regions are known as
      Intrinsically Unstructured Proteins (IUP). IUP have been associated with a wide
      range of protein functions, along with roles in diseases characterized by protein
      misfolding and aggregation. RESULTS: Identifying IUP is important task in
      structural and functional genomics. We exact useful features from sequences and
      develop machine learning algorithms for the above task. We compare our IUP
      predictor with PONDRs (mainly neural-network-based predictors), disEMBL (also
      based on neural networks) and Globplot (based on disorder propensity).
      CONCLUSION: We find that augmenting features derived from physiochemical
      properties of amino acids (such as hydrophobicity, complexity etc.) and using
      ensemble method proved beneficial. The IUP predictor is a viable alternative
      software tool for identifying IUP protein regions and proteins.

PMID- 18831800
TI  - Analyzing adjuvant radiotherapy suggests a non monotonic radio-sensitivity over
      tumor volumes.
AB  - BACKGROUND: Adjuvant Radiotherapy (RT) after surgical removal of tumors proved
      beneficial in long-term tumor control and treatment planning. For many years, it
      has been well concluded that radio-sensitivities of tumors upon radiotherapy
      decrease according to the sizes of tumors and RT models based on Poisson
      statistics have been used extensively to validate clinical data. RESULTS: We
      found that Poisson statistics on RT is actually derived from bacterial cells
      despite of many validations from clinical data. However cancerous cells do have
      abnormal cellular communications and use chemical messengers to signal both
      surrounding normal and cancerous cells to develop new blood vessels and to
      invade, to metastasis and to overcome intercellular spatial confinements in
      general. We therefore investigated the cell killing effects on adjuvant RT and
      found that radio-sensitivity is actually not a monotonic function of volume as it
      was believed before. We present detailed analysis and explanation to justify
      above statement. Based on EUD, we present an equivalent radio-sensitivity model.
      CONCLUSION: We conclude that radio sensitivity is a sophisticated function over
      tumor volumes, since tumor responses upon radio therapy also depend on cellular
      communications.

PMID- 18831801
TI  - Rates of microfilarial production by Onchocerca volvulus are not cumulatively
      reduced by multiple ivermectin treatments.
AB  - Regular distribution of ivermectin reduces onchocerciasis transmission and
      morbidity by killing, within humans, the microfilarial stage of the parasite
      (microfilaricidal effect). In addition, ivermectin exerts a so-called
      embryostatic effect by which microfilarial production by the adult female worm
      becomes suppressed during a number of weeks after treatment. To assess the
      overall effect of ivermectin on onchocerciasis transmission and evaluate the
      likelihood of local elimination of the infection it is important to estimate the
      magnitude of the anti-fertility effect over the course of a treatment programme.
      Estimates of the effect of repeated drug treatments on the production of
      microfilariae by adult Onchocerca volvulus were obtained by developing a model
      that was fitted to data collected from three hyperendemic communities in
      Guatemala, where eligible residents received ivermectin twice per year for two
      and a half years. The data consist of microfilarial load measurements in the
      skin, collected just before each six-monthly treatment during the programme. The
      model that is developed describes the dynamics of an individual host's expected
      microfilarial load over the 30-month study period. We adopt a Bayesian approach
      and use Markov chain Monte Carlo (McMC) techniques to fit the model to the data.
      Combining estimates from the three villages, average microfilarial production in
      the first six months post-treatment was reduced by ~64% of its pre-treatment
      level, regardless of values chosen for the pre-ivermectin fertility rate within
      plausible ranges. Increased adult worm death rate after treatment (to mimic
      removal of macrofilariae via nodulectomy during the programme) resulted in a
      smaller estimated magnitude of the embryostatic effect (rate of microfilarial
      production was reduced by ~58% of pre-ivermectin value). After subsequent
      treatments, the rate of microfilarial production appeared to be similarly
      decreased. The data and analyses therefore do not support the hypothesis of a
      cumulative effect of multiple ivermectin treatments on microfilarial production
      by female worms.

PMID- 18831859
TI  - Loratadine provides early symptom control in seasonal allergic rhinitis.
AB  - Allergic rhinitis (AR) affects approximately 500 million people worldwide, and
      prevalence is increasing. Second-generation nonsedating antihistamines are first
      line treatments for seasonal AR (SAR). This study was performed to evaluate early
      SAR symptom relief with second-generation antihistamines through a retrospective
      analysis of previously published data. In this study, 835 subjects aged 12-60
      years with a > or = 2-year history of SAR were randomized to receive loratadine,
      10 mg, once daily; fexofenadine, 60 mg, twice daily; or placebo for 7 days. Each
      subject recorded the severity of five symptoms of SAR on a scale of 0-3. This
      primary post hoc efficacy analysis was the mean change from baseline in daily
      average A.M./P.M. reflective and instantaneous total symptom score (TSS) on days
      2 and 3. Significantly greater mean reductions from baseline were shown with
      loratadine compared with fexofenadine in average A.M./P.M. reflective TSS on days
      2 (-3.51 versus -2.84, respectively; p < 0.002) and 3 (-3.80 versus -3.19,
      respectively; p = 0.007) and in average A.M./P.M. instantaneous TSS on day 3 (
      3.68 versus -3.15, respectively; p = 0.022). Similar results were noted in
      average A.M./P.M. reflective and instantaneous total nasal symptom scores and for
      10 of 20 individual symptom time points (p < 0.05). Loratadine was significantly
      more effective than placebo for all time points (p < 0.001). Early, sustained
      symptom relief was seen with loratadine, suggesting that it may be more effective
      for treating SAR symptoms.

PMID- 18831860
TI  - Tubular ectasia of the rete testis: a diagnostic dilemma.
AB  - Tubular ectasia of the rete testis is a pathologically benign process with
      complex and varied aetiology. It must be differentiated from neoplastic disease
      of the testis clinically with patient age, mode of presentation, tumour marker
      status and the characteristic ultrasound and Doppler study findings. Awareness
      and diagnosis of this clinical entity can prevent unnecessary surgical
      intervention in these patients.

PMID- 18831861
TI  - A case of intramural oesophageal dissection secondary to nasogastric tube
      insertion.
AB  - Intramural oesophageal dissection is a rare disorder, caused by the interposition
      of a divisive force between the mucosal and muscular layers of the oesophagus,
      leading to their separation. We present a case of intramural oesophageal
      dissection, secondary to the accidental iatrogenic intramural insertion of a
      nasogastric tube. We discuss the aetiologies, presentation, investigation and
      treatment of intramural oesophageal dissection, and make recommendations on the
      management of suspected oesophageal perforation with prophylactic nasogastric
      tube insertion. We also discuss other complications associated with nasogastric
      tube insertion, and how these may be avoided.

PMID- 18831862
TI  - Managing acrometastases treatment strategy with a case illustration.
AB  - The hand is the site of a great variety of benign lesions and, rarely, of
      malignant lesions. Acrometastasis can be the first manifestation of occult
      malignancy. Frequently, these lesions present in a similar way to benign
      conditions leading to erroneous diagnosis and inappropriate treatment. When
      located in the finger, the most frequent cause is lung cancer, while in the toes
      it is due to genito-urinary tumours. Awareness of the possibility of metastatic
      disease during orthopaedic assessment is essential to decrease patient morbidity.
      A case that was referred to our institution with a single metastasis in a digit
      from occult gastric adenocarcinoma is used to illustrate the way these lesions
      are managed. The diagnostic difficulties are summarised and an overview of
      literature was performed to determine management pathways to aid others in the
      treatment of these case.

PMID- 18831863
TI  - Very late local recurrence of Ewing's sarcoma--can you ever say 'cured'? A report
      of two cases and literature review.
AB  - We report two rare cases of very late local recurrence of Ewing's sarcoma,
      occurring 16 years and 19 years after treatment of the primary tumour. In both
      cases, disease remission had been achieved. Both patients originally underwent
      non-surgical combined modality therapy following initial diagnosis and both were
      rendered disease-free. After a long latent phase, both started experiencing
      unexplained local symptoms. These were investigated at their local hospital but
      tumour recurrence was not initially considered as a cause of these symptoms. The
      two patients were eventually referred back to our institution after the diagnosis
      of recurrent Ewing's sarcoma was established. Both have successfully undergone
      complete excision of the recurrences and are receiving postoperative adjuvant
      therapy. These cases highlight the need to remain vigilant for local recurrence,
      however long after the initial diagnosis.

PMID- 18831864
TI  - Henoch-Schonlein purpura with ischaemic bowel.
AB  - Henoch-Schonlein purpura is a vasculitis affecting small arterial vessels.
      Occasionally, cases are referred for a general surgical opinion due to bowel
      involvement in the form of abdominal pain with or without rectal bleeding.
      However, surgical intervention is rarely required. We describe a case of Henoch
      Schonlein purpura in a young man who went on to develop ischaemic bowel requiring
      resection.

PMID- 18831865
TI  - Defunctioning ileostomy following restorative proctocolectomy.

PMID- 18831866
TI  - www.Accurate information for varicose vein patients.com?
AB  - INTRODUCTION: The aim of this study was to review the information available to
      the public regarding the treatment of varicose veins on dedicated UK-based
      websites. PATIENTS AND METHODS: Websites were identified by using the Google
      search engine. All identified websites were examined, noting the range of
      treatments explained and their stated potential complications. Website ownership
      was also recorded. RESULTS: A total of 49 websites were identified, belonging to
      individual physicians (21), private clinics or groups (15), national institutions
      (4) and device/drug manufacturers (4). Five websites were simply redirecting
      portals and, hence, were excluded from further analysis. Treatment methods
      discussed were conventional surgery (32), endovenous laser [EVLA] and/or
      radiofrequency ablation [RFA] (31), and ultrasound-guided foam sclerotherapy
      [UGFS] (27). Only 19 websites (43%) discussed all treatment methods.
      Complications mentioned following surgery were: cutaneous nerve damage (56%),
      recurrence (56%), infection (53%), bleeding (41%) and venous thrombo-embolism
      (38%). Complications following EVLA/RFA were: cutaneous nerve damage (42%),
      recurrence (42%), venous thrombo-embolism (39%) and burns (35%). Complications
      following UGFS were: pigmentation (59%), venous thrombo-embolism (48%),
      ulceration (41%), recurrence (41%), allergy (26%) and visual disturbance (26%).
      CONCLUSIONS: Over 50% of the websites examined did not mention all the management
      methods now available for varicose veins. More importantly, the majority of the
      websites did not warn of the common complications of intervention. Currently,
      information on the Internet cannot be relied upon to supplement informed consent
      and may actually generate unrealistic patient expectations.

PMID- 18831867
TI  - Whose appendicectomy?--Do laparoscopic appendicectomies impair SHO training?
AB  - INTRODUCTION: Open appendicectomy is an ideal procedure for junior surgical
      trainees to develop operative skills. However, in recent years, we have noticed a
      decline in the number of appendicectomies performed by basic surgical trainees
      and a shift towards increasing use of laparoscopic appendicectomy. The aim of
      this study was to determine whether the growing popularity of laparoscopic
      appendicectomy is having a detrimental impact on the training experience of SHOs.
      PATIENTS AND METHODS: We undertook a retrospective review of all cases of
      appendicectomies performed in one district hospital over a 7-year period (August
      1999 to August 2006.) A standard performa was used to extract data from the
      original case notes of these patients relating to the operating surgeon and
      technique. RESULTS: Data were obtained for 857 appendicectomies. Between February
      2002 and July 2003, there was a significant decline in the proportion of
      appendicectomies performed by SHOs from 78.7% to 29.3% (P < 0.001). Either side
      of this decline there were no significant changes in the proportion of SHO
      appendicectomies. The number of appendicectomies performed laparoscopically only
      began to rise after February 2004, with a year-on-year increase. The number of
      appendicectomies performed by SHOs remained stable during this time. No
      laparoscopic appendicectomy was performed by an SHO. CONCLUSIONS: We found no
      evidence that the popularisation of laparoscopic appendicectomy has contributed
      to the decline of appendicectomies performed by SHOs. Nevertheless, with the
      continual rise in popularity of this procedure, it is important to balance
      training opportunities for both junior and higher surgical trainees.

PMID- 18831868
TI  - The cost of shoulder arthroscopy: a comparison with national tariff.
AB  - INTRODUCTION: 'Payment by results' was introduced with the aim of providing each
      trust with a transparent and fair remuneration for the work done. Hospitals are
      paid a tariff for each Healthcare Resource Group (HRG). The tariff is calculated
      at a national level, by means of a complex manipulation of historic financial
      data. However, the financial viability of a hospital relies on these payments and
      so accuracy is vital. PATIENTS AND METHODS: We conducted a cost analysis of
      shoulder arthroscopic procedures carried out at an elective orthopaedic unit.
      This unit is self contained and well audited, providing an unique opportunity to
      make a more accurate cost analysis. We calculated the cost of the facility,
      consumables/implants, anaesthetics and staff pay. This was then compared with the
      amount paid to the trust. RESULTS: All arthroscopic operations performed at our
      institution attract a tariff of pound 1780. Our cost of a subacromial
      decompression was pound 1307, a profit of pound 473. A rotator cuff repair was
      pound 2672, a loss of pound 892. CONCLUSIONS: The tariff is inaccurate. The
      arthroscopic HRG is too general and fails to address the extra time and expense
      of equipment some procedures utilise. We found cost was very sensitive to length
      of operation. Delays and even teaching can make a 'profitable operation' lose
      money for the trust.

PMID- 18831869
TI  - Assessment of magnification of digital pelvic radiographs in total hip
      arthroplasty using templating software.
AB  - INTRODUCTION: Templating of pelvic radiographs traditionally involved using
      implant-company provided acetates which assumed a magnification of 115-120%. With
      the introduction of digital imaging, many departments are becoming filmless.
      Templating software has been designed to allow on-screen templating of digital
      images. Knowledge of the true magnification of the image is required for accurate
      measurement. PATIENTS AND METHODS: Fifty consecutive postoperative pelvic
      radiographs were analysed using templating software. The implanted component was
      measured using an assumed magnification factor of 115%. The template image was
      then reset to the known component size, and the magnification factor was adjusted
      until the template covered the true component. RESULTS: An assumed magnification
      factor of 115% oversized the acetabular component by a mean of 6 mm (three
      component sizes) in all 50 components. The mean true magnification in our
      department was 127%. CONCLUSIONS: Validation of the true magnification produced
      by a radiology department using templating software is a simple and reproducible
      technique. It is recommended to all departments using digital images and
      templating software. Assumption of a magnification factor of 115% risks
      oversizing components by 6 mm.

PMID- 18831870
TI  - From small acorns--developing a laparoscopic colorectal surgical service.
AB  - INTRODUCTION: Randomised controlled trials have shown that laparoscopic
      colorectal surgery is equal in terms of safety to open surgery. Benefits have
      been seen for length of stay, blood loss, immune suppression and analgesia
      requirements. The aim of this study was to assess the safety and feasibility of
      introducing laparoscopic colorectal surgery to our unit. PATIENTS AND METHODS:
      Prospectively collected cases of all patients undergoing laparoscopic colorectal
      surgery between July 2003 and July 2007 were reviewed. RESULTS: A total of 143
      patients (75 males and 68 females) with a mean age of 65.8 years (range, 21-95
      years) underwent surgery. Laparoscopic resection for colorectal malignancy was
      performed in 93 patients (65%). The conversion rate for all cases was 14.7%. Mean
      operative time was 203 min (range, 100-400 min), with a mean blood loss of 180
      ml. The mean number of lymph nodes in malignant cases was 13.8 with clear
      resection margin in all but one case. The mean postoperative stay was 5.6 days
      (median, 4 days; range, 2-35 days). UKCCR standard for lymph node retrieval was
      achieved in 62.6% of cases. There were four postoperative deaths. The overall 30
      day morbidity rate was 21.7%. The service is consultant-led with 9.8% of cases
      performed by senior trainees and 37% of procedures performed by two consultants.
      CONCLUSIONS: Laparoscopic colorectal surgery is technically feasible and safe in
      our hands. Although operative time is longer, this is counterbalanced by shorter
      hospital stay. The results from this series support the findings of others and
      continuing development of this service.

PMID- 18831871
TI  - Clipless technique of laparoscopic cholecystectomy using the harmonic scalpel.

PMID- 18831874
TI  - Blunt splenic trauma.

PMID- 18831875
TI  - Costs of additional cover.

PMID- 18831876
TI  - Targeted training for tube thoracostomy.

PMID- 18831878
TI  - Chronic fatigue syndrome and the central nervous system.
AB  - An increasing amount of neuroimaging evidence supports the hypothesis that
      chronic fatigue syndrome patients have structural or functional abnormalities
      within the brain. Moreover, some neurotrophic factors, neurotransmitters and
      cytokines have also been evaluated in order to elucidate the mechanism of
      abnormal neuropsychic findings in chronic fatigue syndrome. In this review, we
      suggest that the focal point of chronic fatigue syndrome research should be
      transferred to the central nervous system.

PMID- 18831879
TI  - Adjuvant chemotherapy in oesophageal cancer: a meta-analysis and experience from
      the Shanghai Cancer Hospital.
AB  - Whether adjuvant chemotherapy increases survival of oesophageal cancer patients
      has been widely debated. The present study used meta-analysis software to combine
      data from six studies up to July 2007 that were found and selected as suitable,
      comprising a total of 1001 oesophageal cancer patients. The results indicated
      that adjuvant chemotherapy did not significantly improve outcome in oesophageal
      cancer patients. A trend towards improved outcome from adjuvant chemotherapy was
      found in lymph node-positive patients, but did not reach significance. In our own
      study including 270 oesophageal cancer patients, adjuvant chemotherapy did not
      improve overall patient survival, but did improve survival for patients with
      metastases in cervical and/or celiac lymph nodes (stage IVa). Although our study
      had the largest patient sample, more prospective clinical trials with large
      numbers of patients are necessary to confirm the value of adjuvant chemotherapy
      in stage IVa patients.

PMID- 18831880
TI  - Traumatic optic neuropathy therapy: an update of clinical and experimental
      studies.
AB  - Serious injury to the optic nerve, including direct and indirect events, induces
      significant visual loss and even blindness. For the past decade corticosteroids
      and/or optic canal decompression surgery have been widely embraced therapeutic
      paradigms for the treatment of traumatic optic neuropathy. There is little
      clinical evidence, however, to support the effectiveness of these strategies,
      raising questions about the efficiency of current therapy for improving visual
      outcomes. Recently, experimental studies have yielded a wealth of information
      related to the protection and regeneration of retinal ganglion cells, showing
      promise for the development of novel and effective treatments for optic nerve
      injury.

PMID- 18831881
TI  - Brain tumour stem cells and neural stem cells: still explored by the same
      approach?
AB  - Brain tumour stem cells (BTSCs) are chiefly responsible for the in vivo long-term
      growth and recurrence of malignant gliomas and may be a potential treatment
      target. They resemble neural stem cells (NSCs), so their self-renewal and
      differentiation are currently investigated by the same methods used to study
      NSCs. There are, however, essential differences between these cell types: in many
      cases the marker expression pattern of BTSCs does not match the CD133(+)/NSE(
      )/FAP(-) pattern of NSCs; BTSC tumourigenicity is independent of marker
      expression; and while attachment, serum-containing medium and withdrawal of
      mitogens (epidermal growth factor [EGF] and basic fibroblast growth factor
      [bFGF]) are essential to induce NSCs to differentiate, they do not affect BTSC
      tumourigenicity. Evidence implies that research on the renewal and
      differentiation of BTSCs should be orientated towards tumourigenicity and is
      essentially a pharmaceutical problem. Such an approach may contribute to the
      development of an accurate definition of BTSCs and to the search for selective
      differentiation-inducing drugs for BTSCs.

PMID- 18831882
TI  - Reduction in cerebral atrophy associated with ethyl-eicosapentaenoic acid
      treatment in patients with Huntington's disease.
AB  - Ultra-pure ethyl-eicosapentaenoic acid (ethyl-EPA), a semi-synthetic ethyl ester
      of eicosapentaenoic acid, is associated with clinical improvement in motor
      functioning in Huntington's disease. The aim was to determine the extent to which
      it might reduce the rate of progress of cerebral atrophy. High-resolution
      cerebral magnetic resonance imaging scans were acquired at baseline, 6 months and
      1 year in up to 34 patients with stage I or II Huntington's disease who took part
      in a randomized, double-blind, placebo-controlled trial of ethyl-EPA. For each
      subject and each pair of structural images, the two-timepoint brain volume change
      was calculated in a double-blind manner. Significant group-level reductions in
      brain atrophy were observed in the head of the caudate nucleus and the posterior
      thalamus. These findings show that treatment with ethyl-EPA is associated with
      significant reduction in brain atrophy, particularly in the caudate and thalamus.
      No other drug tested in Huntington's disease has shown this effect.

PMID- 18831883
TI  - Apnoea-hypopnoea index during rapid eye movement and non-rapid eye movement sleep
      in obstructive sleep apnoea.
AB  - This study investigated the differences in apnoea-hypopnoea index (AHI) during
      rapid eye movement (REM) sleep (AHI-REM) and AHI during non-REM (NREM) sleep (AHI
      NREM) in patients with obstructive sleep apnoea (OSA). Nocturnal polysomnography
      was performed in 102 Japanese OSA patients and their AHI along with a variety of
      other factors were retrospectively evaluated. Regardless of the severity of AHI,
      mean apnoea duration was longer and patients' lowest recorded oxygen saturation
      measured by pulse oximetry was lower during REM sleep than during NREM sleep.
      Approximately half of the patients (n = 50) had a higher AHI-NREM than AHI-REM.
      In subjects with AHI >or= 60 events/h, AHI-NREM was significantly higher than AHI
      REM. On multivariate logistic regression, severe AHI >or= 30 events/h was the
      only predictor of a higher AHI-NREM than AHI-REM. This may indicate that
      important, but unknown, factors related to the mechanism responsible for the
      severity of OSA are operative during NREM sleep.

PMID- 18831884
TI  - Anatomical variations of coronary ostia, aortocoronary angles and angles of
      division of the left coronary artery of the human heart.
AB  - Classic anatomical dissection of 150 heart specimens from adults aged 18 - 80
      years was performed. Anatomical variations were studied in: (i) the position of
      the ostium of the left coronary artery; (ii) the angle between the proximal
      segment of the left coronary artery and the longitudinal axis of the aorta and
      between the circumflex and the anterior descending branches; (iii) the angle
      between the anterior descending artery and the diagonal branches, and between the
      diagonal and circumflex branches in trifurcation of the left coronary artery;
      (iv) the position of the ostium of the right coronary artery in the right
      coronary sinus of Valsalva; (v) the angle between the initial part of the right
      coronary artery and the longitudinal axis of the aorta; and (vi) the position of
      the initial part of the left coronary artery relative to the coronary groove.
      Knowledge of and the ability to recognize and identify the variety of sites of
      origin of coronary arteries, aortocoronary angles and angles of division of the
      left coronary artery of the human heart may help to overcome potential
      difficulties in cardiosurgical procedures, such as aortic valve replacement and
      reinsertion of coronary arteries.

PMID- 18831885
TI  - Comparison of three warming devices for the prevention of core hypothermia and
      post-anaesthesia shivering.
AB  - The efficacy of forced air warming with a surgical access blanket in preventing a
      decrease in core temperature during anaesthesia and post-anaesthesia shivering
      (PAS) was compared with two widely used interventions comprising forced air
      warming combined with an upper body blanket, and a circulating water mattress, in
      a prospective, randomized double-blind study. A total of 90 patients undergoing
      total abdominal hysterectomy were studied, 30 in each group. Core temperature was
      measured 15, 30, 45, 60, 90 and 120 min after induction of anaesthesia. PAS was
      evaluated every 5 min after emergence from anaesthesia over a period of 1 h. Core
      temperature fell in all three groups compared with the baseline, but forced air
      warming using a surgical access blanket was more effective than the other warming
      methods in ameliorating the temperature decrease. The surgical access blanket was
      also superior to the circulating water mattress in reducing PAS.

PMID- 18831886
TI  - Analgesic and chondroprotective effects of risedronate in osteoarthritis assessed
      by electroalgometry and measurement of collagen type II fragments in urine.
AB  - We evaluated the effect of the bisphosphonate, risedronate, on pain and cartilage
      metabolism in 33 patients with osteoarthritis of the knee, randomized into two
      groups. Group RC was treated with risedronate (2.5 mg/day) and calcium (900
      mg/day); group C received calcium (900 mg/day) alone. Pain on exercise was
      estimated using a subjective visual rating scale (VRS) and an electroalgometric
      method of measuring decrease in skin impedance, previously shown to be indicative
      of pain. We measured urinary excretion of cartilage-specific collagen type II
      fragments as a marker of cartilage degradation. Multiple regression analysis
      revealed that pain alleviation as measured by skin impedance, but not VRS, was
      associated with a decrease in collagen fragment excretion. This suggests that,
      for pain evaluation, reduction in skin impedance may have a greater physiological
      basis compared with VRS-based evaluation. We consider that the chondroprotective
      and analgesic effects of risedronate may be related.

PMID- 18831887
TI  - Rat parathyroid hormone 1-34 signals through the MEK/ERK pathway to induce
      cardiac hypertrophy.
AB  - This study aimed to characterize the role of the mitogen-activated protein kinase
      (MAPK) kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway in
      cardiac hypertrophy induced by parathyroid hormone (PTH). Various concentrations
      of rat PTH1-34 were used to induce hypertrophy in neonatal rat ventricular
      cardiomyocytes, and the effects were compared with control cells and those
      treated with PD98059, a selective inhibitor of MEK1. Hypertrophy was assessed in
      terms of cell diameter, atrial natriuretic peptide (ANP) mRNA expression and
      protein synthesis; the MEK/ERK pathway was assessed by measuring levels of
      phosphorylated ERK1/2. Treatment with PTH1-34 at 100 nM for 24 h effectively
      induced cardiac hypertrophy (increased cell diameter, protein synthesis and ANP
      mRNA expression) and also increased levels of phosphorylated ERK1/2 compared with
      normal control cells. Treatment with PTH1-34 plus PD98059 significantly
      attenuated these changes. These results demonstrate that inhibition of the
      MEK/ERK pathway blocks PTH1-34-induced cardiac hypertrophy, suggesting that PTH1
      34 might signal through the MAPK pathway to induce hypertrophy in cardiomyocytes.

PMID- 18831888
TI  - The effect on the recovery profile of a change from enflurane to desflurane
      during the latter part of anaesthesia.
AB  - This study compared emergence and recovery characteristics after either enflurane
      anaesthesia or crossover from enflurane to desflurane anaesthesia. At an
      estimated 1 h prior to the end of operation, enflurane was either reduced (group
      E, n = 23) or replaced with desflurane (group X, n = 23). At the end of the
      operation, emergence and recovery characteristics of the two groups were
      compared. The crossover technique accelerated recovery compared with enflurane
      anaesthesia. The time taken for the eyes to open in response to painful pinching
      or a verbal command, and to regain awareness of age and name, were significantly
      shorter after crossover anaesthesia than after enflurane anaesthesia. The digit
      symbol substitution test and serial seven test scores were significantly better
      in patients subjected to crossover anaesthesia than in those subjected to
      enflurane anaesthesia. We conclude that, during surgery, the substitution of
      enflurane with desflurane in the latter part of anaesthesia can improve recovery.

PMID- 18831889
TI  - Combination of ultra-low dose bupivacaine and fentanyl for spinal anaesthesia in
      out-patient anorectal surgery.
AB  - This study investigated whether the addition of 25 microg fentanyl to an ultra
      low (sub-anaesthetic) dose of intrathecal bupivacaine provides adequate
      anaesthesia for out-patient anorectal surgery, without increasing side-effects or
      delaying hospital discharge. Patients were randomly allocated to receive 2.5 mg
      0.5% bupivacaine plus 25 microg fentanyl (group BF, n = 18) or 5 mg 0.5%
      bupivacaine alone (group B, n = 17). There were no significant differences in
      intra-operative outcomes, but mean recovery and discharge times were
      significantly shorter in group BF. There were no between-group differences in
      hypotension, bradycardia or respiratory depression and post-operative
      complications were comparable, apart from pruritus which was significantly more
      frequent in group BF. Fewer patients requested analgesic medication in the early
      post-operative period in group BF than in group B. In conclusion, 25 microg
      intrathecal fentanyl added to ultra-low dose (2.5 mg) bupivacaine provided good
      quality spinal anaesthesia and reduced post-operative analgesic requirement in
      patients undergoing ambulatory anorectal surgery.

PMID- 18831890
TI  - Tramadol as a local anaesthetic in tendon repair surgery of the hand.
AB  - This double-blind pilot study compared the local anaesthetic effects of tramadol
      plus adrenaline with lidocaine plus adrenaline during surgery to repair hand
      tendons. Twenty patients were randomly allocated to receive either 5% tramadol
      plus adrenaline (n = 10) or 2% lidocaine plus adrenaline (n = 10). Injection site
      pain and local skin reactions were recorded. At 1-min intervals after injection
      of the anaesthetic agent, the degree of sensory blockade was assessed by the
      patient reporting the extent to which they felt a pinprick, light touch and a
      cold sensation. Pain felt during surgical incision was also recorded. There was
      no difference in the quality of sensory blockade or the incidence of side effects
      between the two groups. Only patients treated with tramadol did not require
      additional post-operative analgesia. A combination of tramadol plus adrenaline
      provided a local anaesthetic effect similar to that of lidocaine plus adrenaline.

PMID- 18831891
TI  - Deterministic dynamics in neuronal discharge from pallidotomy targets.
AB  - The non-linear dynamic specificity of the firing pattern discharged from neurons
      of the internal globus pallidus (GPi) was investigated by recording their
      spontaneous firing using a microelectrode during posteroventral pallidotomy in
      eight patients with Parkinson's disease. Raw data from the cells were processed
      to extract spiking events (discharges above a selected threshold) and the
      interspike interval was measured. Using the unstable periodic orbits extraction
      method, significant period-1, -2 and -3 orbits were identified in burst firing
      discharged from the GPi cells in all eight patients, suggesting that
      deterministic dynamics exist in the timing of the discharges. As well as
      providing a useful peri-operative technique for locating posteroventral
      pallidotomy targets in Parkinson's disease, this method also provides a promising
      basis for investigating characteristic neuronal discharges in other regions of
      the brain and for various other neurological disorders.

PMID- 18831892
TI  - Effects of 2-deoxy-D-glucose on proliferation of vascular smooth muscle cells and
      endothelial cells.
AB  - 2-Deoxy-D-glucose (2-DG) is a glucose analogue that has been proposed for cancer
      therapy due to its cytostatic properties. Its effect on the proliferation of
      smooth muscle cells and endothelial cells has not been fully clarified. The aims
      of this study were to investigate the effects of 2-DG on the proliferation of
      porcine aortic endothelial cells (PAEC) and porcine smooth muscle cells (PSMC),
      to establish an overview of its dose-dependent inhibitory capacity and to examine
      whether the short-term incubation of cells with 2-DG has an impact on cell
      proliferation in culture. Our results showed a dose-dependent significant
      inhibitory effect on proliferation, which was more pronounced in PSMC than in
      PAEC. Even after short-term incubation of cells with 2-DG, relevant inhibition of
      proliferation was documented. The clinical application of 2-DG might be a
      promising concept by inhibiting cells that show a potentially rapid proliferation
      in response to non-malignant stimuli, such as smooth muscle cells after
      intracoronary stenting.

PMID- 18831893
TI  - Effect of inhibition of the central nucleus of the amygdala and drug experience
      on the regions underlying footshock-induced reinstatement of morphine seeking.
AB  - This study assessed the effect of inhibition of the central nucleus of the
      amygdala (CeA) and drug experience on brain regions underlying footshock-induced
      reinstatement of morphine-seeking behaviour in rats. The difference in time spent
      in two chambers of a place preference apparatus was used to measure morphine
      conditioned place preference. Fos was measured as a marker of neuronal activation
      in the ventral bed nucleus of the stria terminalis (BNSTv) and ventral tegmental
      area (VTA). Footshock was found to enhance Fos expression in the BNSTv regardless
      of drug experience. In the VTA, morphine and footshock had an interactive effect
      on the increase in Fos expression. Inhibition of the CeA decreased Fos expression
      in the BNSTv regardless of drug experience, whereas in the VTA this effect only
      occurred in morphine-treated rats. These results suggest that drug experience has
      no differential effect on the BNSTv however morphine produces footshock
      sensitization in the VTA. CeA inhibition modulates the footshock-induced activity
      of these regions of the brain and attenuates reinstatement of drug seeking
      behaviour.

PMID- 18831894
TI  - Construction and identification of an antisense glucose transporter-1 plasmid.
AB  - Our aim was to construct a pcDNA3.1(+) eucaryotic expression system vector
      containing the antisense glucose transporter-1 (Glut-1) gene. Total RNA was
      isolated from human Hep-2 laryngeal carcinoma cells, and the Glut-1 and antisense
      Glut-1 sequences were amplified by polymerase chain reaction. Expression plasmids
      containing the sense and antisense cDNA were constructed using the pcDNA3.1(+)
      vector. The resulting sense and antisense vectors, pcDNA3.1(+)-Glut-1 and
      pcDNA3.1(+)-antiGlut-1, respectively, were examined by restriction analysis and
      DNA sequencing. The pcDNA3.1(+)-antiGlut-1 was subsequently transfected into Hep
      2 cells. AntiGlut-1 mRNA expression was detected, indicating the successful
      construction of an antisense Glut-1 plasmid capable of transfecting Hep-2
      laryngeal carcinoma cells. These data provide a firm basis for additional studies
      using the plasmid pcDNA3.1(+)-antiGlut-1 to determine its therapeutic potential
      for the treatment of laryngeal carcinoma.

PMID- 18831895
TI  - Expression of c-kit protein and mutational status of the c-kit gene in
      osteosarcoma and their clinicopathological significance.
AB  - We examined c-kit protein expression and mutations of the c-kit gene in 40 human
      osteosarcoma samples to their relationship with clinicopathology and prognosis of
      the disease. The expression of c-kit protein was evaluated by
      immunohistochemistry and single-strand conformational polymorphism was performed
      to evaluate c-kit gene mutations in exons 11 and 17. Expression of c-kit protein
      occurred in 25 (62.5%) osteosarcoma samples. Patients with osteosarcomas with
      higher c-kit protein expression levels were significantly more likely to
      experience local disease recurrence and had a significantly lower survival time
      than patients with lower c-kit expression. We found no evidence of mutations in
      exons 11 or 17. This study suggests that c-kit protein expression might serve as
      a prognostic marker for osteosarcoma, however exons 11 and 17 might not be
      suitable targets for osteosarcoma treatments based on suppression of c-kit
      tyrosine kinase activity.

PMID- 18831896
TI  - Cellular distribution of tumour suppressor protein p53 and high-risk human
      papillomavirus (HPV)-18 E6 fusion protein in wild-type p53 cell lines.
AB  - Human papillomaviruses (HPVs) are very important pathogens that can be classified
      as high- and low-risk types based on the lesions they cause. Mucosal high-risk
      HPV E6 can target and degrade the tumour suppressor p53, hence it is recognized
      as the major cause of cervical cancer, however, due to a lack of reliable anti-E6
      antibodies, the distribution of high-risk HPV E6 protein remains elusive. The
      present study, therefore, used a mammalian green fluorescent protein (GFP)
      expression system to express GFP-18 E6 fusion proteins in wild-type p53 cells,
      SMMC-7721 and HCT116, in order to trace the location and expression of HPV E6 and
      p53 protein. Following transfection, expression of GFP-18 E6 was found to be
      located in the nucleus, and endogenous wild-type p53 was also located there with
      GFP-18 E6.

PMID- 18831897
TI  - Eprosartan in the primary prevention of cardiac allograft vascular disease: a
      double-blind prospectively randomized study using intravascular ultrasound.
AB  - The angiotensin blocker (ARB) eprosartan (600 mg once daily) and the calcium
      antagonist diltiazem (90 mg twice daily) were studied in a 24-month prospective,
      randomized, double-blind trial involving 53 heart transplant patients. The study
      compared their effects on the development of post-transplant cardiac allograft
      vasculopathy, a condition that frequently impairs long-term post-transplantation
      survival and where angiotensin blockers might be expected to play a preventive
      role. From baseline to month 12, the mean plaque volume increased by 7.7 mm(3)
      for eprosartan-treated patients and by 34.4 mm(3) for diltiazem-treated patients,
      but the eprosartan-related trend for reduced myointimal hyperplasia was not
      statistically significant. The trend in favour of eprosartan for secondary
      parameters (mean intimal index, vessel volume, lumen volume and coronary flow
      reserve) also failed to reach significance. The lack of effect might be due to a
      lower than planned sample size and observation periods due to recruitment
      difficulties. A larger study is required to confirm these preliminary findings.

PMID- 18831898
TI  - Effects of celecoxib and nimesulide on the proliferation of ectopic endometrial
      stromal cells in vitro.
AB  - The effects of cyclooxygenase 2 (COX-2) selective inhibitors on the proliferation
      of ectopic endometrial stromal cells in vitro were investigated. Ectopic
      endometrial stromal cells were treated with either celecoxib or nimesulide for 24
      and 48 h. The results showed that (i) both celecoxib and nimesulide inhibited the
      proliferation of ectopic endometrial stromal cells in vitro in a time- and dose
      dependent manner; (ii) the expression of prostaglandin E(2) was significantly
      inhibited by both celecoxib and nimesulide in a dose-dependent manner; (iii) the
      percentage of apoptotic cells was significantly higher for cells treated with
      celecoxib or nimesulide than for untreated cells; and (iv) the percentage of the
      cells in the G(0)/G(1) phase increased after the cells were treated with either
      agent in a dose-dependent manner. These data suggest that celecoxib and
      nimesulide inhibited proliferation of ectopic endometrial stromal cells by
      inducing apoptosis and blocking the cell cycle at the G(0)/G(1) phase.

PMID- 18831899
TI  - Efficacy of a high-dose aprotinin regimen for reducing transfusion requirements
      and inflammatory responses in adult cardiac surgery.
AB  - This study evaluated and compared the risks and effects to the inflammatory
      response of low- and high-dose aprotinin regimens. Between January and June 2006,
      patients scheduled for cardiac surgery using cardiopulmonary bypass were enrolled
      and randomly allocated to either low- (n = 15) or high-dose (n = 13) aprotinin
      groups. The incidences of mortality and adverse events were comparable in both
      groups. Post-operative creatinine levels and blood loss were not significantly
      different between the two groups. With the exception of platelets, the counts of
      transfused allogenic blood products were not significantly different between the
      groups. Interleukin (IL)-6, IL-10, soluble tumour necrosis factor II receptor,
      and interferon-gamma levels increased in both groups compared with baseline, but
      no significant intergroup differences were detected. In conclusion, high- and low
      dose aprotinin had similar effects in the reduction of mediastinal bleeding and
      attenuation of systemic inflammatory responses, and high-dose aprotinin therapy
      could be used without any increased adverse effects.

PMID- 18831900
TI  - Mesenchymal stem cells as a gene delivery system to create biological pacemaker
      cells in vitro.
AB  - Pacemaker cells differ from common cardiomyocytes due to the presence of a
      spontaneous depolarization process during the diastolic phase of the cardiac
      cycle. This is due to hyperpolarization-activated cyclic nucleotide-gated (HCN)
      channels, which are responsible for providing an inward current. Genetically
      engineered mesenchymal stem cells (MSCs) were transfected with hHCN4 genes using
      lentiviral transfection, and their potential use as biological pacemaker cells
      was investigated. In addition to expressing an anticipated high level of the
      hHCN4 gene, MSCs transfected with hHCN4 genes also expressed characteristic hHCN4
      protein, a cardiac pacemaker-like current and were capable of increasing the
      spontaneous beating rate of co-cultured cardiac myocytes. Control MSCs did not
      exert these effects. It is hypothesized that genetically engineered MSCs
      transfected with hHCN4 genes by lentiviral transfection can be modified to be
      cardiac pacemaker cells in vitro.

PMID- 18831901
TI  - Using MRI to determine painful vertebrae to be treated by kyphoplasty in multiple
      level vertebral compression fractures: a prospective study.
AB  - A prospective study in 35 osteoporotic patients with 120 multiple-level vertebral
      compression fractures (VCFs) assessed the use of magnetic resonance imaging (MRI)
      to determine painful vertebrae for treatment with kyphoplasty (KP). A total of 51
      vertebrae were identified as painful and selected for KP based on changes in MRI
      signal intensity between T1-weighted, T2-weighted and short tau inversion
      recovery MRI. Efficacy was assessed by the mean change in anterior/middle
      vertebral body height, Cobb's angle, a visual analogue pain scale and the
      Oswestry Disability Index at pre-operative, post-operative and final follow-up
      assessments. Significant improvements in all efficacy measures were observed at
      the postoperative versus pre-operative assessments; no significant differences
      were observed between post-operative and final follow-up assessments. It is
      concluded that painful vertebrae can be determined by MRI signal intensity
      changes and their selection for KP can improve outcomes in patients with multiple
      level VCFs.

PMID- 18831902
TI  - The pattern of visual impairment in patients with pituitary adenoma.
AB  - This retrospective study aimed to identify the pattern of visual impairment in
      pituitary adenoma patients. Patients' eyes were categorized into four groups
      according to their visual acuity score. Trans-sphenoidal hypophysectomy was
      performed on all patients. Significant differences between groups were evaluated
      for visual field defects, visual symptoms duration, degree of suprasellar
      extension and tumour pathology. In the 201 patients (402 eyes) evaluated, 166
      eyes had impaired visual acuity (45 eyes, < 4.0; 43 eyes, 4.0 - 4.4; and 78 eyes,
      4.5 - 4.8), 236 eyes scored > 4.8 and were considered to be free of this
      disorder. A linear correlation was found between visual field defects and visual
      acuity score. Duration of visual symptoms between visual acuity groups was not
      significant. Suprasellar extension (measured by Hardy grades) was significant
      between visual acuity groups and may be the main cause of visual acuity loss in
      pituitary adenoma patients. Non-functional pituitary adenomas tended to affect
      visual acuity more than adenomas with other pathological diagnoses which are
      adrenocorticotropic hormone and prolactin. Further investigation is required to
      clarify visual loss cause in pituitary adenoma patients.

PMID- 18831903
TI  - The role of inflammation in atrial fibrillation following open heart surgery.
AB  - This study investigated the role of systemic inflammation in the development of
      atrial fibrillation (AF) after coronary artery bypass grafting (CABG). CABG was
      performed using cardiopulmonary bypass in 77 patients. Pre-operative AF was
      present in six patients (7.8%) and postoperative AF developed in 13 (18.3%) of
      the 71 patients with pre-operative sinus rhythm. Post-operative mediastinal
      drainage was significantly increased in patients with post-operative AF compared
      with those with sinus rhythm. Plasma E-selectin, P-selectin and vascular cell
      adhesion molecule levels were not significantly different between patients with
      pre- and post-operative sinus rhythm, those with pre-operative sinus rhythm and
      post-operative AF, and those with pre- and post-operative AF. There were
      significant differences between pre- and post-operative C-reactive protein,
      interleukin (IL)-6 and IL-10 levels within all three groups, but no differences
      in these parameters between the groups. Thus, in all groups there were
      significant alterations in mediators indicative of systemic inflammation
      following CABG, but comparisons between the groups revealed no differences
      predictive of AF.

PMID- 18831904
TI  - The Angio-Seal arterial closure device for early ambulation after elective
      percutaneous coronary intervention in patients receiving low-dose enoxaparin.
AB  - This study evaluated the efficacy and safety of use of the Angio-Seal vascular
      closure device deployment for early ambulation (2 h) after elective percutaneous
      coronary intervention in 143 consecutive patients receiving either intravenous
      low-dose enoxaparin (0.5 mg/kg) or unfractionated heparin (UFH). The initial
      success rate of Angio-Seal(trade mark) deployment was 98.6%, with no significant
      difference between the UFH group (98.9%) and the enoxaparin group (98.0%). In
      hospital and clinic outcomes were evaluated in the 141 patients with successful
      Angio-Seal deployment. During hospitalization, there were no deaths, myocardial
      infarction, urgent target vessel revascularization or bleeding events in either
      group; three patients in the UFH group and none in the enoxaparin group had minor
      vascular complications (differences not significant). In clinic follow-up, two
      patients in the UFH group and none in the enoxaparin group had major vascular
      complications (differences not significant). Routine use of the Angio-Seal(trade
      mark) for early ambulation in patients receiving intravenous low-dose enoxaparin
      compared with UFH provides promising efficacy and safety for daily practice.

PMID- 18831905
TI  - Comparison of sagittal and frontal plane alignment after open- and closed-wedge
      osteotomy: a matched-pair analysis.
AB  - High tibial osteotomy (HTO) is a procedure for treating medial compartment
      osteoarthritis (OA) of the varus deformed knee. Frontal and sagittal alignment
      after closed- and open-wedge HTO were compared radiologically in a matched-pair
      study. The mean intra-operative frontal plane correction (FT axis) was +7.5
      degrees for closed-wedge HTO and +8 degrees for open-wedge HTO; it increased by
      +0.5 degrees in closed-wedge HTO and decreased by -0.5 degrees in open-wedge HTO
      at last follow-up. Post-operatively, tibial slope had decreased by -0.5 degrees
      in closed-wedge HTO and increased significantly by +3 degrees in open-wedge HTO.
      Both techniques effectively and safely corrected varus deformity. A high degree
      of stability of the frontal plane correction was noted, however a significant
      change in the tibial slope after open-wedge HTO was observed post-operatively. As
      no loss of correction was shown, it may be related to the surgical technique
      rather than to the implant used.

PMID- 18831906
TI  - Relative effects of telmisartan, candesartan and losartan on alleviating arterial
      stiffness in patients with hypertension complicated by diabetes mellitus: an
      evaluation using the cardio-ankle vascular index (CAVI).
AB  - Using the cardio-ankle vascular index (CAVI) as an indicator, we assessed
      improvement of arterial stiffness in 95 outpatients with hypertension complicated
      by type 2 diabetes mellitus who were treated orally for >or= 12 months with
      telmisartan 40 mg/day, losartan 50 mg/day or candesartan 8 mg/day. At 1 year, in
      the telmisartan and losartan groups CAVI did not change whereas in the
      candesartan group CAVI showed a statistically significant decrease of 2.70%.
      Although telmisartan is believed to enhance the activity of peroxisome
      proliferator-activated receptor (PPAR-gamma) in vitro, it did not ameliorate
      arterial stiffness in our patients. Candesartan, however, improved arterial
      stiffness independently of blood pressure lowering and without PPAR-gamma agonist
      action, possibly by direct action resulting from its potent affinity and binding
      capacity for the angiotensin II type 1 receptor. We conclude that candesartan is
      a potentially useful therapy against arterial stiffness in hypertensive patients
      with type 2 diabetes mellitus.

PMID- 18831907
TI  - Use of tunnelled catheters in haematological malignancy patients with
      neutropenia.
AB  - This prospective study analysed 83 patients (age 45 +/- 17 years) with
      haematological neoplasms, implanted with 93 tunnelled catheters, who were
      neutropenic or developed neutropenia during treatment. Catheters were implanted
      in the right (n = 82) or left (n = 11) jugular vein by the same surgical team
      using the same technique. They remained in place for 124 +/- 88 days: 29% were
      removed due to infection; 18% due to treatment termination and 2% due to
      mechanical problems. Seventeen patients died with catheters in place. At 30, 60,
      90, 120 and 200 days mean catheter duration rates were 82%, 75%, 65%, 60% and
      35%, respectively, and freedom from catheter removal due to infection was 92%,
      88%, 80%, 77% and 67%, respectively. Patient diagnosis and history of previous
      catheter infection did not increase catheter infection risk, but patients
      undergoing stem cell transplantation had an increased infection risk. Tunnelled
      catheters can be used in high-risk patients with neutropenia. Systemic infections
      can be managed in most patients without catheter removal.

PMID- 18831908
TI  - Clinical usefulness of a bolus calculator in maintaining normoglycaemia in active
      professional patients with type 1 diabetes treated with continuous subcutaneous
      insulin infusion.
AB  - This observational study assessed metabolic control in young, active
      professionals with type 1 diabetes treated with continuous subcutaneous insulin
      infusion (CSII) with or without the use of a bolus calculator. Eighteen patients
      aged 19 - 51 years with diabetes duration of 6 - 22 years were included; eight
      patients used a bolus calculator and 10 did not. Metabolic control was assessed
      by glycosylated haemoglobin (Hb(A1c)) measurements and blood glucose profiles. A
      continuous glucose monitoring system (CGMS) was also used by three patients from
      each group. Mean Hb(A1c) and fasting blood glucose levels were not significantly
      different between the two groups, but mean post-prandial blood glucose was
      significantly lower in bolus calculator users than non-users. The CGMS showed
      more blood glucose levels within the target range in bolus calculator users than
      non-users, but statistical significance was not achieved. In conclusion, a bolus
      calculator may help to improve postprandial blood glucose levels in active
      professional type 1 diabetes patients treated with CSII, but does not have a
      major impact on Hb(A1c) levels.

PMID- 18831909
TI  - The views of doctors on registration trials in a Japanese rural area: a survey of
      medical institutions registered to the Tokushima Network for Clinical Trials.
AB  - Tokushima University Hospital has established the Tokushima Network for Clinical
      Trials (TNCT) to promote clinical trials in the area in collaboration with the
      Tokushima Medical Association. The present study investigated the views of
      doctors towards registration trials in the TNCT. A questionnaire was provided to
      49 clinics/hospitals registered to the TNCT in 2006 and 38 (78%) responded. It
      revealed that 48% of doctors were aware of registration trials and 87% were
      favourable towards participating as investigators in them. They considered close
      contact with developmental drugs, advancement of therapy and the opportunity to
      learn about state-of-the-art treatment as benefits of participation. The main
      areas of difficulty included management of adverse reactions and patients'
      refusal to take part. Many doctors wanted more opportunity to learn about trial
      related issues such as regulations. The survey indicates that the TNCT needs to
      develop the infrastructure and enlighten participants to promote registration
      trials in this rural regional area.

PMID- 18831910
TI  - Polymorphisms in genes encoding the serotonin and dopamine pathways in two
      sisters with metachromatic leukodystrophy.
AB  - Metachromatic leukodystrophy (MLD) is a metabolic disease that has recently been
      investigated as a model for the study of psychosis. We report on two sisters with
      adult-type MLD who developed psychiatric symptomatology, but differed in their
      expression of psychotic and depressive symptoms. Association studies have
      indicated that polymorphisms in genes encoding the serotonin and dopamine
      transporters and receptors are related to the symptomatology of schizophrenia
      and/or depression; hence both sisters were genotyped for some of these candidate
      genes. The sisters shared dopamine receptor D(2) (DRD(2)) c.1047GG (p.311Ser/Ser)
      and c.-141Cins/ins polymorphisms, which are significantly associated with
      schizophrenia, but differed in the serotonin transporter gene-linked polymorphic
      region and serotonin receptor 1A (5-HT(1A)) c.-1019C to G polymorphisms, which
      may have increased the elder sister's susceptibility to depressive symptoms. Much
      bigger samples would be needed to gain enough statistical power to develop any
      hypotheses. This is the first report on genotyping MLD patients for candidate
      genes for psychiatric disorders, although MLD has been proposed as a model for
      schizophrenia.

PMID- 18831911
TI  - Postpartum severe sinus bradycardia following methylergonovine administration.
AB  - The case is reported of a 30-year-old multigravida, with insignificant history
      and stable vital signs, admitted to the labour room for normal vaginal delivery
      of twins. She received combined spinal epidural analgesia (bupivacaine plus
      fentanyl) for 3 h. Following uneventful delivery she received 0.2 mg
      methylergonovine maleate, intramuscularly. Nausea and vomiting occurred 70 min
      after placenta delivery, heart rate decreased, arterial blood pressure increased
      and there was chest pain. After excluding cardiac ischaemia, 0.5 mg atropine
      sulphate was administered intravenously. Chest pain improved but heart rate and
      blood pressure increased more than expected. The patient had mild headache and
      nausea, and antiemetic 4 mg ondansetron was given intravenously. Continuous
      monitoring for 4 h showed spontaneous chest pain relief and blood pressure
      improvement. In conclusion, serious delayed side-effects arising from
      methylergonovine maleate can occur in young, normal patients and close monitoring
      is required. Intravenous atropine sulphate following methylergonovine maleate
      administration may lead to severe hypertension and tachycardia.

PMID- 18831912
TI  - Isolated intracranial Rosai-Dorfman disease mimicking suprasellar meningioma:
      case report with review of the literature.
AB  - Rosai-Dorfman disease (RDD) is an idiopathic histiocytic proliferation affecting
      the lymph nodes. Isolated intracranial RDD is rare and usually appears as a well
      defined, dural-based lesion without lymphadenopathy. The clinical and
      radiological features of intracranial RDD are similar to meningioma.
      Histopathology and immunohistochemistry are essential for a definitive diagnosis.
      This is a report of a 43-year old male with isolated intracranial RDD, which
      manifested as a suprasellar meningioma. The clinical, radiological and
      pathological aspects of the disease are discussed within the context of a review
      of previously reported cases.

PMID- 18831913
TI  - Palatine tonsil schwannoma: correlation between clinicopathology and computed
      tomography features.
AB  - We describe the case of a 37-year old male who presented with a schwannoma in his
      right palatine tonsil. The tumour and tonsil were surgically removed transorally.
      Tonsillar schwannomas are slow growing, and the main symptoms were a foreign body
      feeling in the throat, dysphagia and snoring. The presence of a round, well
      defined mass lesion with heterogeneous density on computed tomography (CT) may
      aid in differentiation from other tonsillar tumours. The CT findings in the
      reported case were different to those of schwannomas in other locations; the
      particular CT manifestations of tonsillar schwannomas seem to relate to the
      various pathological changes seen within the tumour.

PMID- 18831914
TI  - Cryptococcal lymphadenitis as a manifestation of immune reconstitution
      inflammatory syndrome in an HIV-positive patient: a case report and review of the
      literature.
AB  - Cryptococcus neoformans infections are typically associated with T-cell
      deficiencies, including acquired immunodeficiency syndrome (AIDS). Although
      highly active antiretroviral therapy (HAART) has strongly reduced AIDS-related
      opportunistic infections, the restoration and reactivation of CD4+ cells can
      induce an immune reconstitution inflammatory syndrome (IRIS), consisting in a
      deregulated inflammatory response to latent infectious pathogens and/or to their
      residual antigens. Cryptococcal lymphadenitis has occasionally been documented in
      IRIS. Here we report a case of histology- and culture-negative cryptococcal
      lymphadenitis associated with IRIS in an adult AIDS patient with a history of
      disseminated cryptococcosis, after the start of fully adherent HAART. Appropriate
      diagnosis was established on nested-PCR and sequence analysis of the interspacer
      region 2 of C. neoformans ribosomal DNA, and detection of slow-growing
      blastospores in enrichment cultures of fine-needle lymph node aspirate. Review of
      recent literature and our case findings suggest that IRIS-associated cryptococcal
      lymphadenitis is more likely the flare up of a latent infection rather than an
      immunopathological response to residual antigen of unviable cryptococci.

PMID- 18831915
TI  - Chemokines and bone remodeling.
AB  - Bone remodeling is characterized by spatial and temporal coupling of bone
      resorption and formation and is necessary for skeletal growth and normal bone
      structure maintenance. Imbalance of this process is related to metabolic bone
      disorders such as osteoporosis or rheumatoid arthritis. For this reason, bone
      remodeling is under the control of several local and systemic factors, including
      molecules of the immune system. The importance of the interplay of both the
      skeletal and immune systems is reflected by the emerging interdisciplinary
      research field, called osteoimmunology, focused on common aspects of osteology
      and immunology. This review focuses on the role of inflammatory mediators, such
      as cytokines in bone remodeling and, in particular, a subfamily of chemotactic
      cytokines or chemokines which are involved not only in several aspects of
      physiological bone remodeling but also in pathological bone disorders, such as
      rheumatoid arthritis or osteoporosis. Understanding the role of inflammation and
      chemokines will provide new insights for the treatment of diseases affecting both
      skeletal and immune systems, by the development of new therapeutic strategies
      targeting common inflammatory mediators.

PMID- 18831916
TI  - Strategies to overcome obstacles to successful immunotherapy of melanoma.
AB  - The immunogenicity of malignant melanomas has been recognized by the observed
      recruitment of tumor-specific cytotoxic T-cells (CTL), leading to the
      identification of several melanoma associated antigen (MAA). However, numerous
      strategies to treat melanoma with immunotherapy have resulted in only partial
      success. In this editorial, we discuss recent data related to the ability of
      tumors to elude immune responses. We therefore discuss different strategies to
      induce a clinically effective immune response. These approaches include 1)
      immunostimulation: including peptide/protein based vaccines, dendritic cell
      vaccines, and adoptive cell transfer; and 2) overcoming immunosuppression,
      including targeting of checkpoint molecules such as CTLA-4, circumventing the
      activity of Tregs, and assuring antigen expression by tumor cells (thwarting
      antigen silencing). Finally, we discuss recent advances in gene therapy,
      including adoptive therapy with engineered T cell receptors (TCRs). These issues
      lead to the conclusion that successful immunotherapy in malignant melanoma
      requires a combination of strategies aimed at both inducing immunostimulation and
      blocking immunosuppression.

PMID- 18831917
TI  - Antioxidative role of interleukin-6 in septic lung injury in mice.
AB  - We have previously demonstrated the protective role of interleukin (IL)-6 against
      septic lung injury induced by lipopolysaccharide (LPS) using IL-6 knock-out (-/-)
      mice. This protection is mediated, at least partly, through the inhibition of the
      enhanced local expression of proinflammatory cytokines. In the present study, we
      addressed whether IL-6 regulates oxidative stress in the lung generated by LPS
      exposure using IL-6 (-/-) and corresponding wild type (WT) mice. Intraperitoneal
      LPS (1 mg/kg) challenge induced transcriptional expressions of inducible nitric
      oxide synthase and heme oxygenase -1 in the lung of mice with both genotypes. In
      the presence of LPS, these expressions were significantly greater in IL-6 (-/-)
      than in WT mice. Immunohistochemistry also showed that LPS induced a significant
      increase in 8-hydroxy-2'-deoxyguanosine formation in the lung as compared to
      vehicle. Furthermore, the formation was more intense in IL-6 (-/-) than in WT
      mice in the presence of LPS challenge. In the presence of LPS, lipid peroxidation
      in the lung was significantly greater in IL-6 (-/-) than in WT mice. These data
      suggest that the possible mechanisms in which endogenous IL-6 protects against
      septic lung injury induced by LPS involve, at least in part, its antioxidative
      properties.

PMID- 18831918
TI  - A quercetin containing supplement reduces niacin-induced flush in humans.
AB  - Coronary artery disease is associated with increased serum levels of cholesterol,
      triglycerides and LDL, but low levels of HDL. The most potent agent capable of
      reversing this trend is the vitamin nicotinic acid (niacin). However, compliance
      even with extended-release preparations and addition of acetylsalicylic acid
      (ASA) is hampered by the development of a feeling of erythema and burning
      ("flush"), especially on the face. We recently showed that the natural flavonoids
      quercetin and luteolin can eliminate "flush", as well as inhibit both niacin
      induced plasma prostaglandin D2 (PGD2) and serotonin increase in an animal model.
      We conducted a pilot clinical study in humans. Four normal male subjects received
      (a) 1 g immediate release niacin either alone or after (b) the dietary
      formulation (Algonot-plus) containing 150 mg quercetin per capsule. Subjects
      completed a visual scale (1 = no, 5 = worst response) symptom assessment.
      Erythema and burning sensation scores were both 4.75+/-0.50 and lasted for 3.63+/
      1.11 hours. After Algonot-plus administration, both scores were reduced to 2.5+/
      0.58 and lasted only for 1.68+/-0.70 hours. Quercetin also inhibited
      methylnicotinate-induced human mast cell PGD2 release. These preliminary results
      suggest that quercetin could reduce niacin-induced "flush" in humans.

PMID- 18831919
TI  - Interferon gamma-signature transcript profiling and IL-23 upregulation in
      response to Helicobacter pylori infection.
AB  - Helicobacter pylori infection is the major cause of gastroduodenal pathologies
      including gastric cancer. The long persistence of bacteria and the type of immune
      and inflammatory response determine the clinical issue. In this study, the global
      gene expression profile after 6 and 12 months of H. pylori infection was
      investigated in the mouse stomach, using the Affymetrix GeneChip Mouse Expression
      Array A430. Genes related to the inflammatory and immune responses were focused.
      Levels of selected transcripts were confirmed by reverse transcription polymerase
      chain reaction. Twenty- five and nineteen percent of the differentially expressed
      genes observed at 6 and 12 months post-infection respectively, were related to
      immune response. They are characterized by an interferon (IFN)gamma-dependent
      expression associated to a T helper 1 (Th1) polarised response. In-depth analysis
      revealed that an up-regulation of IL-23p19, took place in the stomach of H.
      pylori infected-mice. Strong IL-23p19 levels were also confirmed in gastric
      biopsies from H. pylori-infected patients with chronic gastritis, as compared to
      healthy subjects. Our microarray analysis revealed also, a high decrease of H+K+
      ATPase transcripts in the presence of the H. pylori infection. Association of
      gastric Th1 immune response with hypochlorhydria through the down-regulation of
      H+K+-ATPase contributes to the genesis of lesions upon the H. pylori infection.
      Our data highlight that the up-regulation of IL-23 and of many IFNgamma signature
      transcripts occur early on during the host response to H. pylori, and suggest
      that this type of immune response may promote the severity of the induced gastric
      lesions.

PMID- 18831920
TI  - Impact of porcine Orexin A on glucagon plasma concentrations in pigs.
AB  - In 1998, Orexin A was added to the long list of orexigenic neuropeptides of the
      brain's physiology. Orexin A is involved in the central control of appetite and
      in energy homeostasis, as well as in the regulation of many other physiological
      functions. It is produced by a small cluster of the brain's neurons, located
      mainly in and around the lateral hypothalamic area. This site is known to be
      involved in regulating feeding in mammals. An intracerebroventricular injection
      of Orexin A into the rat's brain causes an impressive increase in the consumption
      of food, while an intravenous injection induces changes on glucagon plasma
      concentrations in rats. In addition, there are signs of changes on glucagon
      plasma concentrations when Orexin A acts on individual pancreatic islets of rats.
      In this study, we investigated the potential effects of the central
      administration of porcine Orexin A on glucagon plasma concentrations in pigs, and
      examined whether these changes are associated with the possible effect of the
      neuropeptide on the enteroinsular axis.

PMID- 18831921
TI  - Involvement of cPLA2 inhibition in dexamethasone-induced thymocyte apoptosis.
AB  - Various molecular mechanisms have been suggested to be involved in dexamethasone
      induced thymocyte apoptosis. In this study we show that pharmacological
      inhibition of cytoplasmic PLA2 in mouse thymocytes for 18 h with arachidonyl
      trifluoromethyl ketone (AACOCF3) (10 microM) and palmitoyl trifluoromethyl ketone
      (PACOCF3) (10 microM) induced a drastic increase of thymocyte apoptosis
      comparable to that observed following Dex (10(-7) M) treatment, while inhibition
      of secretory PLA2 with p-bromophenacyl bromide (pBPB) (20 microM) did not.
      AACOCF3-induced thymocyte apoptosis, similarly to Dex-induced thymocyte
      apoptosis, was eliminated by cell pre-treatment with the PI-PLCbeta inhibitor,
      U73122, but not by the PC-PLC inhibitor D609. These observations were
      corroborated by the ability of AACOCF3, like Dex, to induce a rapid and transient
      increase in DAG generation. In addition, AACOCF3-induced apoptosis involved the
      activation of the acidic sphingomyelinase (aSMase) but not of the neutral
      sphingomyelinase (nSMase), as evaluated by measurements of enzyme activity in
      cell extracts following thymocyte exposure to AACOCF3 and by the ability of
      monensin to inhibit AACOCF3-induced thymocyte apoptosis. In addition, the AACOCF3
      apoptotic effect resulted in an early increase of ceramide levels. AACOCF3
      induced thymocyte apoptosis involved the activation of caspase 3, and cell pre
      treatment with a caspase 3 inhibitor prevented AACOCF3-induced apoptosis. These
      observations suggest that cPLA2 inhibition may have a role in Dex-induced
      thymocyte apoptosis and highlight the importance of cPLA2 activity in thymocyte
      survival.

PMID- 18831922
TI  - Antibodies as predictors of complex autoimmune diseases and cancer.
AB  - The pathologic role of autoantibodies in many autoimmune diseases is widely
      accepted. An enzyme immunoassay was used for measurement of antibodies against
      disease-specific antigens and etiologic agents for cross-reactive antigens
      associated with them. This antibody assay was applied to a panel of antigens for
      the detection of different neuroautoimmune diseases that included multiple
      sclerosis, motor peripheral neuropathies, multifocal motor neuropathy,
      amyotrophic lateral sclerosis, pediatric autoimmune neuropsychiatric disorder
      associated with streptococcal infection. We studied women with pregnancies
      complicated by neural tube defect, neuroborreliosis, autism and patients with
      possible somatic hypermutation. Antibodies were also measured against antigens
      and etiologic agents associated with primary biliary cirrhosis and chronic
      obstructive pulmonary disease. And, finally, antibodies were measured against
      several tumor antigens or peptides which are expressed in prostatic, breast and
      colon tissues. This panel of different autoantibodies was applied to 290 patients
      with neuroautoimmune disorders, cancer, and possible somatic hypermutation. The
      levels of these antibodies against different tissue-specific antigens and
      etiologic agents associated with them were significantly elevated in patients
      versus controls. We hope that this novel 96 antigen-specific ELISA will be used
      in additional studies that will prove its clinical efficacy, not only for the
      early diagnosis of many neuroautoimmune, liver and lung autoimmune disorders, but
      also for prognosis and the implementation of preventive steps for many complex
      diseases.

PMID- 18831923
TI  - In-air micro-particle induced X-ray emission analysis of asbestos and metals in
      lung tissue.
AB  - Inhalation of asbestos increases the risk of lung cancer and pulmonary fibrosis.
      It is difficult to directly assess the distribution and content of inhaled
      particles in lung tissue sections. The purpose of this study is to employ an in
      air micro particle induced X-ray emission (in-air micro-PIXE) system for
      assessment of the spatial distribution and content of asbestos and other metals
      in lung tissue. A proton ion-microbeam from this system was applied to irradiate
      lung tissue of patients with or without asbestosis, tumor tissue from both
      groups, and asbestos fibers (in vitro). The content of each element composing
      asbestos and those of other metals were calculated and their distribution was
      assessed from the characteristic X-ray pattern for each element obtained after
      irradiation. This in-air micro-PIXE system could identify the location of
      asbestos bodies composed of Si, Mg, and Fe in lung tissue sections. Macrophage
      and lymphocytes accumulated in that area. This new system also revealed deposits
      of titanium, nickel, and cobalt in the lung tissues, in addition to asbestos
      bodies. The Si and Fe content were higher in lungs with asbestosis than in lungs
      without asbestosis or in tumor tissue. Analysis of asbestos fibers composed of
      chrysotile, crocidolite, and amosite showed that the ratios of Si, Fe, and Mg
      corresponded with those for the chemical structures. In-air micro-PIXE analysis
      is useful for assessing the distribution and quantities of asbestos bodies and
      also other metals in lung tissue comparing to immune-related cell localizations,
      and is also useful for analysis of standard asbestos fibers.

PMID- 18831924
TI  - Murine models of anaemia of inflammation: extramedullary haematopoiesis
      represents a species specific difference to human anaemia of inflammation that
      can be eliminated by splenectomy.
AB  - In contrast to humans, mice physiologically exhibit extramedullary haematopoiesis
      in the spleen. In spite of this crucial species specific difference not much is
      known about the contribution of extramedullary haematopoiesis to overall
      erythropoiesis in models of anaemia of inflammation (AI). The objective of this
      study is to characterize murine AI with respect to extramedullary haematopoiesis
      and to develop a model more closely resembling human AI. Three different models
      of AI [caecal ligation and puncture (CLP), collagen induced arthritis (CIA) and
      DSS induced chronic colitis (DSSC)] were characterized with respect to red blood
      parameters, iron metabolism and extramedullary haematopoiesis. Arthritic animals
      were splenectomised to prevent extramedullary haematopoiesis. Anaemia caused by
      systemic inflammation was found in all three models. Splenic extramedullary
      haematopoiesis was markedly increased as reflected by increment in spleen weights
      and increase of the red pulp resulting in increased reticulocyte counts.
      Splenectomised arthritic animals did not show increased reticulocyte counts
      indicating that most of the reticulocytes were produced in the spleen. Our
      results demonstrate that murine AI differs from human AI with respect to
      increased splenic extramedullary haematopoiesis. Our data demonstrate that
      induction of AI in splenectomised mice represents a good way to model human AI.

PMID- 18831925
TI  - Quantification of sirolimus and everolimus by immunoassay techniques: test
      specificity and cross-reactivity evaluation.
AB  - The possible cross-reactivity of immunoassays with structurally-related drugs was
      investigated. Innofluor Certican (FPIA) calibrators were measured by using IMx
      Sirolimus assay (MEIA) and MEIA Sirolimus calibrators were analysed by using FPIA
      Certican assay. Drug concentrations were measured in 95 and 100 samples from
      renal transplanted patients (RTP) on sirolimus or everolimus treatment by using
      immunoassays and LC/ESI-MSMS. A high cross-reactivity was found both for MEIA and
      FPIA. High correlation degrees, confirmed by the Bland-Altman and the Eksborg
      tests, were found between drug concentrations measured in real samples by both
      immunoassays (r = 0.909 and r = 0.970, respectively). LC/ESI-MSMS analysis of
      samples containing sirolimus showed no positivity for everolimus. Similarly,
      samples from patients on treatment with everolimus resulted negative as far as
      regards sirolimus. MEIA and FPIA could be considered mutually reliable and
      accurate alternatives for the specific-drug immunoassay. It should be noticed
      that in patients switching from one drug to the other unreal overestimation of
      the blood levels of the current administered immunosuppressant can occur.

PMID- 18831926
TI  - Potential role of culture mediums for successful isolation and neuronal
      differentiation of amniotic fluid stem cells.
AB  - In recent years, the use of stem cells has generated increasing interest in
      regenerative medicine and cancer therapies. The most potent stem cells derive
      from the inner cell mass during embryonic development and their use yields
      serious ethical and methodological problems. Recently, a number of reports
      suggests that another suitable source of multipotent stem cells may be the
      amniotic fluid. Amniotic fluid mesenchymal stem cells (AFMSCs) are capable of
      extensive self-renewal, able to differentiate in specialized cells representative
      of all three germ layers, do not show ethical restriction, and display minimal
      risks of teratomas and a very low immunogenity. For all these reasons, amniotic
      fluid appears as a promising alternative source for stem cell therapy. Their
      recent discovery implies a lack of knowledge of their specific features as well
      as the existence of a protocol universally recognized as the most suitable for
      their isolation, growth and long-term conservation. In this study, we isolated
      stem cells from six amniotic fluids; these cells were cultured with three
      different culture mediums (Mesenchymal Stem Cell Medium (MSCGM), PC-1 and RPMI
      1640), characterized by cytofluorimetric analysis, and then either frozen or
      induced to neuronal differentiation. Even if the immunophenotype seemed not to be
      influenced by culture medium (all six samples cultured in the above-mentioned
      mediums expressed surface antigens commonly found on stem cells), cells showed
      different abilities to differentiate into neuron-like cells and to re-start the
      culture after short/long-term storage. Cells isolated and cultured in MSCGM
      showed the highest proliferation rate, and formed neuron-like cells when sub
      plated with neuronal differentiation medium. Cells from PC-1, on the contrary,
      displayed an increased ability to re-start culture after short/long term storage.
      Finally, cells from RPMI-1640, even if expressing stem cells markers, were not
      able to differentiate in neuron-like cells. Further studies are still needed in
      order to assess the effective role of culture medium for a successful isolation,
      growth, differentiation and storage of AFMSCs, but our data underline the
      importance of finding a universally accepted protocol for the use of these cells.

PMID- 18831927
TI  - C-reactive protein changes in the uncomplicated course of arthroscopic anterior
      cruciate ligament reconstruction.
AB  - The diagnosis of septic arthritis following arthroscopic anterior cruciate
      ligament (ACL) reconstruction is often elusive and can only be confirmed by joint
      aspiration, although arthrocentesis carries a risk for superinfection. C-reactive
      protein (CRP) may prove a useful laboratory test to substantiate clinical
      suspicion. The present study investigated the post-operative variations of CRP in
      58 patients (age range 15-52, median age 25) undergoing ACL reconstruction with
      either bone-patellar tendon-bone (BPTB) or hamstring tendon (HT) who did not
      develop infection at 6 months follow-up. CRP titre was determined on the 1st,
      3rd, 7th, 15th, and 30th post-operative day by immunoprecipitation in patients
      divided according to the type of autograft (BPTB: 13 patients; HT: 45 patients).
      Mean CRP significantly increased on the 1st post-operative day, peaked on the 3rd
      day and decreased on the 7th day, while levels on the 15th and 30th days did not
      differ from baseline. The trend of CRP changes did not differ in relation to the
      type of autograft. The results of our study suggest that close clinical
      surveillance may be advisable when CRP levels deviate from the reference values 2
      weeks after surgery. In these circumstances, suspicion of septic arthritis
      warrants aspiration and culturing in order to avert a diagnostic delay.

PMID- 18831928
TI  - Lack of inflammatory cells in the oral mucosa of subjects undergoing sublingual
      immunotherapy.
AB  - The cells involved in allergic inflammation, such as mast cells, basophils, and
      eosinophils, have been thoroughly studied in the nose, the lungs and the skin,
      demonstrating an evident increase in response to the introduction of the specific
      allergen, while little is known in the mucosal system and particularly in the
      oral mucosa. We investigated such tissue by using the model of sublingual
      immunotherapy (SLIT), by which high doses of the specific allergen enter the
      mouth. Oral biopsies were carried out on seven subjects allergic to grass pollen
      and treated with SLIT by a grass extract. In biopsies carried out before SLIT
      there was a very low number of mast cells and eosinophils both in the epithelium
      and subepithelium layers, and insignificant changes were detected after SLIT.
      These findings show the lack of allergic inflammation in the oral mucosa upon
      contact with the specific allergen and confirm the role of the mouth as a
      tolerogenic site, which is conceivable considering the different attitude of the
      mouth, where the antigens transit to undergo digestion, in respect to the airways
      or the skin, where the antigen absorption is potentially dangerous.

PMID- 18831929
TI  - Immunohistochemical evaluation of global DNA methylation and histone acetylation
      in papillary urothelial neoplasm of low malignant potential.
AB  - A preceding study has shown that karyometry detected subvisual differences in
      chromatin organization status between non-recurrent and recurrent papillary
      urothelial neoplasm of low malignant potential (PUNLMP). The status of chromatin
      organization depends on epigenetic events, such as DNA methylation and histone
      acetylation. The aim of this study is to explore global DNA methylation and
      global histone acetylation in non-recurrent and recurrent PUNLMP. 5
      methylcytosine (5MeC) and acetylated histone H3 lysine 9 (AcH3K9) were
      investigated by immunohistochemistry (IHC) in 20 PUNLMP cases (10 non-recurrent
      and 10 recurrent), in 5 cases of normal urothelium (NU) and in 5 cases of muscle
      invasive pT2 urothelial carcinoma (UC). For global DNA methylation, the mean
      percentage of positive nuclei in the cells adjacent to the stroma increased from
      NU (79%) through non-recurrent and recurrent PUNLMP (86% and 93%, respectively)
      to UC (97%). The percentages of positive nuclei in the intermediate cell layers
      and in the superficial cells in the four groups were similar to those adjacent to
      the stroma. The proportion of nuclei with weak-to-moderate intensity was far
      greater than that of those strongly stained and increased steadily from NU to UC.
      For global histone acetylation, the mean percentage of positive nuclei was
      highest in non-recurrent PUNLMP (i.e. 90%) and lowest in recurrent PUNLMP (i.e.
      81%). In NU and UC the mean percentages of positive nuclei were 84% and 86%,
      respectively. The percentage of positive nuclei decreased from the cell layer
      adjacent to the stroma to the superficial cell layer. The proportion of nuclei
      with weak-to-moderate intensity was slightly greater than that of those strongly
      stained. In comparison with global DNA methylation, the proportion of strongly
      stained nuclei was much higher. In conclusion, there are differences in global
      DNA methylation and histone acetylation patterns between non-recurrent and
      recurrent PUNLMP. Further studies are needed to elucidate the complex interplay
      between chromatin structure, its modifications and recurrence of PUNLMP.

PMID- 18831930
TI  - Inhaled thiamphenicol and acetylcysteine in children with acute bacterial
      rhinopharyngitis.
AB  - Antibiotic abuse for treating rhinopharyngitis induces the occurrence of
      resistant bacteria. As topical drugs might reduce this phenomenon, the aims of
      our study are to evaluate inhaled thiamphenicol associated with acetylcysteine in
      children with acute bacterial rhinopharyngitis and to compare it with the use of
      saline solution. The trial was conducted as randomized, parallel group, and
      single blind. Children, aged 3-6 years, with acute bacterial rhinopharyngitis
      were treated with aerosolized thiamphenicol associated with acetylcysteine (250
      mg: 1/2 vial in the morning and 1/2 vial in the evening) (Group A) or saline
      solution twice daily (Group B), both of them for 5 days. Both treatments were
      administered using a new device: Rinowash. The following parameters were
      assessed: nasal obstruction, mucopurulent rhinorrhea, post-nasal drip, cough,
      sore throat, fever, and cultures. Of 104 patients screened, 90 children, median
      age 3.7 years (44 females and 46 males), completed the study: 60 in Group A and
      30 in Group B. Actively-treated children achieved a significant improvement of
      all parameters, but fewer than the control group. In conclusion, inhaled
      thiamphenicol associated with acetylcysteine may represent a valid treatment for
      acute bacterial rhinopharyngitis in children, as it is effective, safe, economic,
      and simple to use.

PMID- 18831931
TI  - Improvement in relative survival of patients with vasculitis: study of 101 cases
      compared to the general population.
AB  - Immunosuppressive treatment has changed the prognosis of renal vasculitis over
      time, but improvement in prognosis is difficult to analyze in different
      historical periods, and can be better demonstrated by comparison with life
      expectancy of sex- and age-matched people. Long-term survival of 101 patients
      diagnosed with systemic vasculitis at our center from 1975 to 2002 was
      retrospectively evaluated in comparison with that of the Region's age- and sex
      matched population. Patient and kidney survival significantly increased over
      time. Multivariate analyses showed that risks of patient and renal death
      decreased by 10% and 7%, respectively, at each year of follow-up, and increased
      by 6.3% and 5.2% for each year of age. Relative survival significantly improved
      over time, approaching that of the general population for cases diagnosed after
      1993, mainly in women < 60 years (from 0.671 at 5-years in the first period to
      0.916 in the last period), while 5-year-relative-survival was still 0.530 and
      0.682 in men and women greater than 60 years, respectively. Poisson-based
      multinomial analyses confirmed the significant risk of the first periods of
      diagnosis and of dialysis in worsening of the relative survival of patients
      compared to that of the general population. Life expectancy in patients with
      renal vasculitis has improved over time, paralleling a significant increase in
      steroid pulse/cyclophosphamide association therapy and an earlier diagnosis due
      to the introduction of the ANCA test. Relative survival has considerably
      improved, and now approaches that expected in the general population for women,
      but not for men.

PMID- 18831932
TI  - Serum cytokines and bioumoral immunological characterization of psoriatic
      patients in long term etanercept treatment.
AB  - The purpose of this study is to evaluate blood cytokines and immunological
      parameters in psoriatic patients during long-term treatment with Etanercept.
      Forty-five subjects of both sexes affected by psoriasis with or without arthritis
      entered the study and were treated with Etanercept according to international
      standard protocols. Biochemical blood analysis was carried out at baseline and
      during follow-up every second month. In particular, the following parameters were
      kept under control: antinuclear antibodies, anti-nDNA antibodies, anti-histone
      antibodies, blood cell count, circulating lymphocyte subtypes (CD3, CD4, CD8,
      CD16, CD19) and IgE. Cytokine profiles (IL-1-alpha, IL-1-beta, IL-6, IL-8, IL-10,
      IL-12, INF, TNF-alpha) were also evaluated in blood samples during the treatment
      up to 1 year of follow-up. A significant decrease in PASI score (p < 0.01) and in
      several cytokine levels was observed, particularly in IL-1, IL-6, IFN-gamma (p <
      0.01) and to a lesser extent in TNF-alpha (p < 0.05). No statistically
      significant changes were recorded after 1 year of follow-up in blood
      immunological parameters, in particular in ANA titre, CD4/CD8 ratio, IgE levels,
      CD16, CD19 and eosinophils count. In conclusion, long-term treatment with
      Etanercept leads not only to a significant improvement in PASI score, but also to
      significant changes (reduction) in several proinflammatory and modulatory
      cytokines involved in the pathogenesis of the disease; on the other hand, there
      are no effects on immunological or bioumoral parameters showing that etanercept
      modulates rather than suppresses the physiological responses during psoriasis
      treatment.

PMID- 18831933
TI  - Sucralfate modulates uPAR and EGFR expression in an experimental rat model of
      cervicitis.
AB  - Sucralfate is a drug used in the treatment of gastric and duodenal ulcer; it is
      cytoprotective and able to increase the bioavailability of several growth
      factors, modulating the wound healing process. In this study we tested the
      possible therapeutic effect of Sucralfate in the treatment of ulcerative lesions
      occurring in uterine cervix; to investigate such effect we used an experimental
      rat model of cervicitis in which the uPAR and EGFR expression were evaluated.
      Cervicitis was induced in wild and ovariectomized Wistar female rats by an acetic
      acid-soaked tampon. The animals were divided into two main groups (4 and 7 days)
      and Sucralfate was administered topically until the day they were sacrificed. In
      order to distinguish physiological and drug-induced healing, quantitative and
      qualitative uPAR and EGFR expression were evaluated by using Western blot and
      Immunohistochemistry techniques. Western blot analysis demonstrated an increased
      expression of both receptors after 4 days from wounding in wild and
      ovariectomized animals. In particular in ovariectomized animals the expression of
      uPAR and EGFR increased after 4 days while it reduced following the
      administration of Sucralfate. In wild rats the same was observed for uPAR
      expression, while EGFR was different; in fact, its expression increased
      significantly at day 4 in the animals treated with the drug and only at day 7 in
      those untreated. Immunohistochemistry highlighted a noteworthy epithelial
      colocalization of EGFR and uPAR after 4 days in the animals treated with
      Sucralfate. We conclude that Sucralfate can promote the healing of ulcerative
      cervicitis and moreover, it reduces the normal healing time because of its
      modulatory property on uPAR and EGFR expression.

PMID- 18831934
TI  - Antibodies to carbonic anhydrase in patients with connective tissue diseases:
      relationship with lung involvement.
AB  - The aim of this study is to evaluate the presence of antibodies to carbonic
      anhydrase I and/or II (ACAI and ACAII) in patients affected by connective tissue
      diseases (CTD) and to investigate their association with lung involvement
      evaluated by High resolution CT scan (HRCT). Ninety-six patients affected by CTD
      were studied, i.e. 33 rheumatoid arthritis (RA), 8 psoriatic arthritis (PA), 8
      ankylosing spondilitis (AS), 23 Systemic Lupus Erythematosus (SLE), 10 Sjogren
      Syndrome (SS), and 14 Systemic Sclerosis (SSc). ACA were detected by ELISA. The
      lung involvement was evaluated by means of a previously described HRCT score.
      According to a receiver operator characteristic curve, patients were divided into
      those with HRCT score > or = 10 and those with HRCT score < 10, where HRCT score
      > or = 10 was predictive of interstitial lung disease. ACAI and/or ACAII were
      detected in 30/96 patients (31.2%) (P < 0.0001 in comparison with controls). In
      particular, the prevalence of ACAI and/or ACAII was significantly higher in
      patients with RA (P = 0.002), PA (P < 0.0001), SLE (P = 0.0003) and SSc (P <
      0.0001). A positive correlation was found between HRCT scores and CRP or ACAI
      levels (P = < 0.0001 and P = 0.004, respectively). Thirty-nine of 96 patients
      (40.6%) showed a HRCT score > or = 10 and both their CRP and ACAI levels were
      significantly higher when compared with patients showing a HRCT score less than
      10 (P < 0.0006 and P = 0.0009, respectively). Moreover, C3 and C4 complement
      fractions inversely correlated with HRCT scores (P = 0.0004 and P < 0.0001,
      respectively) and lower values of C3 and C4 complement fractions were found in
      patients with HRCT score > or = 10 than in those with HRCT score less than 10 (P
      = 0.014 and P = 0.007, respectively). Due to the lower levels of complement
      fractions detected in patients with HRCT score > or = 10, a possible immune
      complex-mediated pathogenic mechanism of lung involvement could be suggested.

PMID- 18831935
TI  - Sublingual desensitization in patients with wasp venom allergy: preliminary
      results.
AB  - The aim of this paper is to assess in an open prospective pilot case-control
      study the tolerability, safety and efficacy of an ultra-rush sublingual
      immunotherapy (SLIT) protocol with Vespula venom in wasp allergic patients
      compared to subcutaneous immunotherapy (SCIT). Forty-one wasp allergic patients
      were treated with sublingual (SLIT group) or subcutaneous (SCIT group) ultrarush
      immunotherapy with Vespula venom extract. All patients underwent skin tests and
      serum specific IgE and IgG4 detection before enrollment and after 6, 12 and 24
      months of immunotherapy. The SLIT group consisted of 21 (6 females and 15 males)
      patients who received increasing doses of Vespula venom (Aquagen, ALK-Abello)
      until the final dose of 30 drops of extract in 3 hours, containing 100,000 SQ
      U/ml. The maintenance dose was of 10 drops of pure venom extract 3 times a week,
      for a total dose of 100,000 SQ-U weekly (corresponding to 100 microgram of venom
      extract). The SCIT group consisted of 20 patients (16 males and 4 females) who
      were treated with subcutaneous ultrarush immunotherapy with Vespula venom extract
      (Pharmalgen, Alk-Abello). Patients received 101.1 microgram of Vespula venom in 3
      hours and were treated with 100 microgram of wasp venom monthly. During the
      ultrarush sublingual treatment 2 patients (9.5%) experienced mild side-effects.
      Specific IgE and specific IgG to wasp venom did not show any significant
      modification. Four patients were field-stung by a wasp during the treatment (for
      a total of 6 stings). Two patients (3 stings), with a previous clinical history
      of a grade III and IV reaction, did not experience any reaction. One patient,
      with a previous grade II reaction, showed a large local reaction. The fourth
      patient, with a previous grade III reaction, was re-stung twice (after 12 and 24
      months) with two systemic reactions (SR) (mild throat constriction). During the
      ultrarush SCIT phase, 3 (15%) patients experienced side-effects: 2 of them showed
      a large local reaction and 1 had headache and stomach ache. Specific IgE showed a
      significant (P = 0.001) increase after 6 months of treatment and then returned to
      baseline levels while specific IgG showed a significant (P = 0.001) increase
      after 6, 12 and 24 months in comparison with baseline. Nine patients were field
      stung during the treatment: 8 of them experienced large local reactions; one
      patient (11%) experienced an SR (dizziness). Our results, even if in a small
      number of patients, suggest that in patients with Hymenoptera sting allergy SLIT
      could be efficacious with a good tolerability profile when compared to SCIT.
      Larger studies are needed to assess efficacy, safety and tolerability profile of
      wasp venom SLIT.

PMID- 18831936
TI  - Comparison of thermal infrared and laser doppler imaging in the assessment of
      cutaneous tissue perfusion in scleroderma patients and healthy controls.
AB  - In this study we propose a non-invasive method to calculate blood flow by means
      of thermal infrared imaging and bio-heat transfer modeling. The method is able to
      provide high time-resolution series of cutaneous blood flow images with the same
      spatial resolution of the thermal images. The method was tested against a
      standard laser Doppler imaging system, which to date is considered the gold
      standard for non-invasive assessment of cutaneous blood flow, on both healthy
      subjects and patients suffering from systemic sclerosis (SSc; a pathological
      condition with microvessel endothelium injury). Twenty healthy subjects and
      twenty SSc patients simultaneously underwent laser Doppler and thermal imaging of
      the dorsum of the hand. A linear correlation between perfusion values obtained
      with the two methods was found for the healthy control group (R = 0.85, Pearson
      Product Moment Correlation). A significant correlation was not observed for the
      SSc patient group. The results of this study suggest that combined laser Doppler,
      thermal imaging and bio-heat transfer modeling could effectively discriminate
      between healthy vs. impaired conditions of the cutaneous tissue thermal
      properties and cutaneous vasculature. Such method, in addition to providing a
      potential effective imaging-based tool for a variety of biomedical and clinical
      applications ranging from diagnostics to treatment follow-up, may help the
      understanding of the morphological and functional impairment secondary to the
      disease. The thermal imaging-based method provided faster and better time
      resolved imaging of cutaneous perfusion than standard laser Doppler techniques as
      the thermal cameras can provide up to 100 complete 524 x 524 pixel images per
      second, thus allowing real time monitoring of tissue perfusion rates.

PMID- 18831937
TI  - Histological and clinical survey of polylactic-polyglycolic acid and dextrane
      copolymer in maxillary sinus lift: a pilot in vivo study.
AB  - Of various proposed alternatives to autogenous bone, a synthetic, degradable
      copolymer of PLA-GLA and dextrane seems to be a promising biomaterial for
      maxillary sinus lift. Consecutive partially edentulous patients showing severe
      monolateral posterior maxillary atrophy were treated via sinus lift using PLA-GLA
      dextrane copolymer as the sole filler. Delayed implant positioning was performed
      and cores of regenerated tissues and native bone controls were retrieved and
      evaluated by light and electron microscopy, histomorphometry, microhardness and
      qualitative X-ray analysis. Seven sinuses in 7 patients were augmented with PLA
      GLA-dextrane copolymer. Six to nine months after the copolymer 'graft', 17 bone
      cores were retrieved: all histological sections contained newly synthesized,
      mineralized material and new bone in various stages of development.
      Histomorphometry revealed average Trabecular Bone Volume (TBV) values ranging
      from 51% (6 months) to 77% (9 months). Backscattered scanning electron microscopy
      (BSE) in experimental and control samples confirmed histology findings.
      Microhardness values suggested newly formed bone at nine months was not as hard
      as native bone. Ca and P content was similar in 9-month regenerated and native
      bone. Seventeen implants were inserted in the second stage of surgery: resulting
      Implant Success (SR) and Cumulative Success (CSR) up to 3 years were 100%
      following Albrektssons criteria. Sinus lift augmentation using PLA-GLA-dextrane
      copolymer as the sole filler resulted in uneventful surgeries. New bone formation
      was evident histologically and its maturation was still in progress after 9
      months. Successful, staged implant positioning was achieved in regenerated
      tissue.

PMID- 18831938
TI  - The increase of endothelial progenitor cells in the peripheral blood: a new
      parameter for detecting onset and severity of sepsis.
AB  - Sepsis is a clinical syndrome characterized by non-specific inflammatory response
      with evidence of profound changes in the function and structure of endothelium.
      Recent evidence suggests that vascular maintenance, repair and angiogenesis are
      in part mediated by recruitment from bone marrow (BM) of endothelial progenitor
      cells (EPCs). In this study we were interested in whether EPCs are increasingly
      mobilized during sepsis and if this mobilization is associated with sepsis
      severity. Our flow cytometry data demonstrate that in the CD34+ cell gate the
      number of EPCs in the blood of patients with sepsis had a four-fold increase (45
      +/- 4.5% p < 0.001) compared to healthy controls (12 +/- 3.6%) and that this
      increase was already evident at 6 hours from diagnosis (40.6 +/- 4.2 percent),
      reaching its maximum at 72 hours. Also the percentage of cEPCs identified in the
      patients with sepsis (35 +/- 4.6% of the CD34+ cell) was statistically different
      (p < 0.001) compared to that found in the blood of patients with severe sepsis
      (75 +/- 4.9%). In addition, we proved that at six hours after sepsis diagnosis,
      VEGF, CXCL8 and CXCL12 serum levels were significantly higher in septic patients
      compared to healthy volunteers 559 +/- 82.14 pg/ml vs 2.9 +/- 0.6 (p < 0.0001),
      189.8 +/- 67.3 pg/ml 15 vs 11.9 +/- 1.6 (p = 0.014) and 780.5 +/- 106.5 pg/ml; vs
      190.2 +/- 71.4 (p < 0.001). Our data suggest that the cEPC evaluation in
      peripheral blood, even at early times of diagnosis, in patients with sepsis can
      be envisaged as a valuable parameter to confirm diagnosis and suggest further
      prognosis.

PMID- 18831939
TI  - Evaluation by real-time PCR of the expression of S. flexneri virulence-associated
      genes ospB and phoN2 under different genetical backgrounds.
AB  - Under conditions of activated type III secretion Shigella flexneri up-regulates
      the expression of numerous genes, including the virulence plasmid (pINV)-encoded
      ospB and phoN2 genes. ospB and phoN2 are virulence-associated genes which are
      part of a bicistronic transcriptional unit encoding OspB, a protein (effector) of
      unknown function secreted by the type III secretion (TTS) apparatus, and PhoN2
      (apyrase or ATP-diphosphohydrolase), a periplasmic protein involved in polar IcsA
      localization on the surface of S. flexneri. In this work we used real-time PCR to
      measure transcription of ospB and phoN2 of wild-type S. flexneri strain M90T as
      well as of derivative mutants impaired in definite virulence traits. The results
      obtained confirmed and extended previous reports indicating that the expression
      of ospB and phoN2 genes is modulated in a virB-dependent, mxiE-independent manner
      under conditions of non-activated secretion, while their expression is
      considerably induced in a mxiE-dependent manner under conditions of activated
      secretion. That the expression of the ospB-phoN2 operon is up-regulated in
      condition of activated secretion, indicates that probably the expression of these
      two genes might be important, especially during the later stages of infection of
      S. flexneri.

PMID- 18831940
TI  - Virulence traits in Escherichia coli strains isolated from outpatients with
      urinary tract infections.
AB  - This study aims to characterize phenotypic and genotypic virulence traits in
      Escherichia coli strains, isolated from outpatients with urinary tract
      infections, comparing with those obtained from inpatients. Information on the
      pathogenic behavior of the uropathogenic strains was obtained by monitoring
      different biological properties, such as autoagglutination, hemagglutination,
      adhesiveness to and invasion of human bladder (HT1376) cells, biofilm formation,
      phylogenetic grouping, and virulence-related genes. The results show similar
      behavior in the two groups concerning autoagglutination, hemagglutination, and
      biofilm formation. None of the strains examined was invasive. However, in strains
      from outpatients there was an increased adhesion to HT1376 cells compared with
      clinical strains, a significant higher presence of genes codifying for adhesins
      and cell protection factors, and a lower proportion of strains belonging to B1
      group. These findings add further information on the pathogenic traits of
      community E. coli, since strains isolated from the outpatients' group were
      differently "armed" in comparison with those of clinical cases, and more suitable
      to infect healthy individuals.

PMID- 18831941
TI  - Photoallergic contact dermatitis: the 15-year experience of a tertiary reference
      center in a sunny Mediterranean city.
AB  - Photoallergic contact dermatitis (PACD) represents an important entity of
      photodermatoses while photopatch testing is the main diagnostic tool. The main
      goal of this study is to evaluate retrospectively the prevalence of photoallergic
      reactions and the offending agents in Athens during a 15-year period. The medical
      records of all patients with possible PACD between 1992 and 2006 were examined.
      All patients included in the analysis had undergone patch testing and photo
      testing. Contact reactions were detected in 86 out of 207 participants (41.54%),
      while photocontact reactions were identified in 28/207 (13.52%) patients. The
      most common offending photoallergen was promethazine (25%), while chlorpromazine
      and oxybenzone were both detected in 12.5% of cases. PACD represents a unique
      proportion of photodermatoses in a sunny Mediterranean city such as Athens.

PMID- 18831942
TI  - Blood cholesterol concentration measured by CR3000: fingerstick versus venous
      sampling.
AB  - Currently, the clinical practice of desktop or Point of Care (PoC) analyzers for
      lipid measurements has gained wide popularity. Designed to quickly perform
      measurements on microlitre(microL) quantities of blood, these instruments can be
      used in non-laboratory settings, such as physicians offices or field-testing
      sites and can provide measurements in whole blood, serum, or plasma, using either
      venous or capillary blood samples. The aim of this study is to examine the
      relationship between cholesterol determinations in venous and capillary samples
      using the CR3000 PoC system. The study was performed on 21 unselected adult
      volunteers, and no exclusion criteria was adopted. The mean cholesterol
      concentration for the venous blood samples measured was 164 mg/dL. The values
      obtained in the capillary blood samples averaged 168 mg/dL, which is only
      slightly higher (e.g., 2.87%) than the venous sample measurements. Moreover, the
      total variance was statistically similar for venous and capillary measurements (F
      value = 1.199, where the upper critical value of the F distribution is 2.124, p <
      0.05). The results of our study support the concept that CR3000 total cholesterol
      testing can be performed safely and accurately in either venous or capillary
      specimens.

PMID- 18831943
TI  - Prevalence of atopic symptoms among blood donor carriers of mannose-binding
      lectin variant alleles.
AB  - Mannose-binding lectin (MBL) is a C-type soluble collectin involved in the innate
      immune response. Carriers of MBL gene variant alleles (MBLva) have decreased
      plasma concentrations of MBL and increased susceptibility to bacterial and viral
      infections. The aim of the present study is to test the hypothesis that carriers
      of MBLva could have a different frequency of atopic symptoms as compared to wild
      type carriers. A total of 385 consecutively enrolled Caucasian blood donors were
      studied. Blood specimens underwent genomic analysis and genotyping for MBLva by
      polymerase chain reaction (PCR). MBLva carrier status was associated with a
      reduced frequency of allergic rhinitis (OR 0.41 [95% CI 0.2 to 0.8], chi2 = 6.98,
      p =.008). No relationship was found between MBLva carrier status and asthma or
      atopic skin symptoms. MBLva might be one of the host-related genetic factors
      involved in atopic disorders, namely allergic rhinitis.

PMID- 18831944
TI  - Visceral leishmaniasis revealing chronic granulomatous disease in a child.
AB  - We report the first description of visceral leishmaniasis (VL) infection as a
      harbinger of chronic granulomatous disease (CGD) in a 3-year old child. Although
      VL is not frequently suspected in CGD patients, our case emphasises the
      importance of a complete evaluation of the immune system in children presenting
      with VL in order to exclude underlying immunodeficiency states. As the prognosis
      of CGD is poor, with high morbidity and mortality, establishing an early
      diagnosis has important practical implications in the successful treatment of
      these patients. Following the diagnosis, the patient received Human Leukocyte
      Antigen (HLA) identical sibling bone marrow transplantation (BMT). The child is
      now 2 years post-transplant and is in good general conditions with normal blood
      counts, and evidence of full-donor chimerism in repeated fluorescence in situ
      hybridization (FISH) studies.

PMID- 18831945
TI  - Characterization of a Staphylococcus aureus strain showing high levels of biofilm
      formation isolated from a vascular graft: case report.
AB  - A methicillin-susceptible Staphylococcus aureus strain, SA-DZ1, was isolated from
      an infected bypass crossover graft. Its general microbiological features were
      reminiscent of those previously described for the wound Wiley strain. Removal of
      the prosthetic device was necessary to resolve the infection. SA-DZ1 grown under
      different conditions showed a very strong and distinctive biofilm-producing
      phenotype, which was also visualized by confocal laser scanning microscopy. The
      biofilm extracellular matrix was essentially polysaccharidic, as determined by
      differential growth and physicochemical tests. By Multi Locus Sequence Typing
      (MLST), SA-DZ1 was classified as st94, a single locus variant of st8. Several
      other genetic traits assayed by PCR, such as agr-type and the presence of gene
      encoding proteins involved in adhesion and virulence (e.g. ica operon), confirmed
      the identifying features of this clinical isolate.

PMID- 18831946
TI  - Extragenital lichen sclerosus and atrophicus treated with topical steroids and
      retinoids in a child with vitiligo.
AB  - Lichen sclerosus and atrophicus (LSA) most commonly affects the anogenital
      region. Extragenital involvement is rare, and women are reported to be affected 6
      to 10 times more often than men. The aetiology of LSA is unclear, but genetic,
      physiological and environmental factors are thought to be involved. Several lines
      of evidence support the hypothesis of an autoimmune basis for LSA; an increased
      incidence of tissue-specific antibodies and an association with autoimmune
      disorders such as vitiligo, alopecia areata, thyroid disease and pernicious
      anaemia have been reported. We describe a paediatric patient with extragenital
      LSA associated with vitiligo who was successfully treated with topical steroids
      and retinoids.

PMID- 18831947
TI  - Consequences of long-lasting persistent allergic rhinitis in adolescents.
AB  - While it is well known that asthma is characterized by airway remodelling, only
      few studies have investigated this issue in patients affected by allergic
      rhinitis (AR). The aim of the present study is to investigate functional and
      structural consequences of long-lasting persistent AR (PER) in a cohort of
      adolescents. Eighty patients, forty with short-lasting and forty with long
      lasting PER were prospectively and consecutively evaluated both clinically and by
      performing skin prick test, nasal cytology, and rhinomanometry. Eosinophils were
      significantly higher in patients presenting with long-lasting PER rather than in
      those with short-lasting PER (P < 0.0001). The degree of inflammation was
      significantly associated with impaired nasal airflow (rs = -0.81). This study
      provides evidence that adolescents with long-lasting PER may show a progressive
      worsening of nasal function depending on the inflammation.

PMID- 18831948
TI  - Time to full publication of studies of anti-cancer medicines for breast cancer
      and the potential for publication bias: a short systematic review.
AB  - OBJECTIVES: To identify the expected delay between publication of conference
      abstracts and full publication of results from trials of new anti-cancer agents
      for breast cancer and to identify whether there are any apparent biases in
      publication and reporting. DATA SOURCES: Major electronic databases were searched
      to identify randomised controlled trials (RCTs) of the selected interventions for
      the treatment of breast cancer. REVIEW METHODS: A systematic review was conducted
      according to standard methods. Data were extracted from the included studies
      using a predesigned and piloted data extraction template. RESULTS: Six anti
      cancer treatments for breast cancer were included in the review: docetaxel,
      paclitaxel, trastuzumab, gemcitabine, lapatinib and bevacizumab. The literature
      searches generated 1556 references, from which 71 publications were retrieved and
      screened for inclusion. Screening identified 41 publications of 18 RCTs with at
      least one arm of treatment meeting the inclusion criteria for the review. Of the
      18 included RCTs, only four publications (from three RCTs) reported the same
      outcomes in both an abstract and a full publication. Time between the abstract
      and full publication was 5 months in two cases, 7 months in one case and 19
      months in one case (overall mean delay = 9 months). Eleven trials were identified
      that have not currently published in a full publication the data presented in an
      abstract or conference proceeding. The duration between publication of the
      abstracts and the end of August 2007 varied from 3 months to 38 months (mean
      delay 16.5 months). The longest delays in publication were for trials
      investigating gemcitabine (38 months) or bevacizumab (33 months). Observational
      analysis of the published and unpublished trials did not indicate any particular
      biases in terms of whether positive results were more likely to be fully
      published than non-significant ones. CONCLUSIONS: It was surprising that only
      three of the 18 relevant RCTs had one or more full papers that reported the same
      outcome measures (and stage of analysis) as an earlier conference abstract.
      However, a limitation of this review is the small number of studies included.
      With a larger sample size than that in the present report, investigation into the
      effect of publication delay on decision-making might be feasible. Future research
      should include extension of this work to other anti-cancer drugs and
      investigation into the reasons for lengthy delays to full publication noted for
      some trials.

PMID- 18831949
TI  - Prioritisation of infectious diseases in public health--call for comments.
AB  - In order to allocate rationally resources for research and surveillance of
      infectious diseases at the level of the German public health institute (RKI), we
      prioritised pathogens by public health criteria. After screening the relevant
      literature we developed a standardised methodology including a three-tiered
      scoring system for selected pathogens. The pathogens were rated in four
      categories containing a total of 12 criteria: burden of disease including
      incidence, severity, mortality; epidemiologic dynamic including outbreak
      potential, trend, emerging potential; information need including evidence on risk
      factors/groups, validity of epidemiologic information, evidence for pathogenesis;
      international duties and public attention; health gain opportunity including
      preventability, treatability. For each criterion a numerical score of +1, 0 or -1
      was given and each criterion received a weight by which the numerical score of
      each criterion was to be multiplied. The total weighted scores ranged from +22.7
      (influenza) to - 64.4 (cholera) with the median being -22.9 (rubella). Relevant
      changes were observed between weighted and unweighted scores. The chosen approach
      proved to be feasible and the result plausible. However, in order to further
      improve the methodology we invite experts to give feedback on the methodology via
      a structured web-based questionnaire at www.rki.de/EN > Prevention of infection >
      Infectious Disease Surveillance > Pathogen prioritization. Results of this survey
      will be included in a modification of the methodology. .

PMID- 18831950
TI  - Methicillin-resistant Staphylococcus aureus nasal carriage among healthy
      employees of the Hellenic Air Force.
AB  - The prevalence of methicillin-resistant Staphylococcus aureus nasal carriage
      among 959 healthy employees of the Hellenic Air Force was investigated from
      November 2004 to October 2005. Nine participants were found to be colonised by
      methicillin-resistant Staphylococcus aureus (MRSA) (SCCmec type IV). Eight of the
      MRSA isolates were PVL-negative and belonged to ST30 by MLST, while the remaining
      one isolate was PVL-positive and classified as ST-80.

PMID- 18831951
TI  - Increase in hepatitis A cases in the Czech Republic in 2008--preliminary report.
AB  - The public health protection authorities in the Czech Republic report a rise in
      cases of viral hepatitis A (HAV) since the end of May 2008. In total, as many as
      602 HAV cases have been reported in 2008 until the end of calendar week 39 (28
      September).

PMID- 18831952
TI  - Community-wide outbreak of hepatitis A in Latvia, in 2008.
AB  - Since November 2007, an increase in the number of reported hepatitis A cases has
      been observed in Latvia. The aim of this report is to provide an update on the
      descriptive epidemiology of hepatitis A in Latvia and suggest some possible
      explanations of the recent increase in incidence.

PMID- 18831953
TI  - Melamine contamination of dairy products in China--public health impact on
      citizens of the European Union.

PMID- 18831954
TI  - Relationship between immunoglobulin isotype response to Plasmodium falciparum
      blood stage antigens and parasitological indexes as well as splenomegaly in
      sympatric ethnic groups living in Mali.
AB  - This study aimed to assess correlations between anti-malarial antibody levels and
      differences in malariometric characteristics, seen between two sympatric ethnic
      groups, the Fulani and the Dogon, living in Mali. Plasma levels of anti-malarial
      IgE, IgG, IgG1-4 and total IgE were determined in asymptomatic individuals, of
      the above mentioned groups, and were correlated to malariometric indexes.
      Significantly higher levels of anti-malarial IgE, IgG, IgG1-3 and total IgE were
      detected in the Fulani individuals as compared to the Dogon. No difference in
      plasma levels of malaria specific IgG4 was noted between the two groups. Within
      the Fulani, an increase in total IgE levels was associated with the presence of
      infection. As the IgG4 level increased, the number of clones decreased in the
      Fulani individuals. A positive correlation between elevated levels of anti
      malarial IgG and IgG3 and splenomegaly was noted only within the Fulani group. No
      other correlations between antibody levels and parasite prevalence, clone numbers
      or spleen rates were observed in any of the communities. These results suggest
      that the magnitude of antibody response against Plasmodium falciparum may not be
      as important as it is believed to be. Instead, the fine specificity or function
      of the response might be more critical in protection against malaria disease.

PMID- 18831955
TI  - Brazilian studies on the genetics of Schistosoma mansoni.
AB  - The parasite Schistosoma is known to exhibit variations among species, strains
      and genera, such as, the levels of infectivity, pathogenicity and immunogenicity.
      These factors may differ among parasite populations according to the local
      epidemiological conditions. Diversity observed in Schistosoma mansoni from
      different geographical regions or within individuals of the same region can be
      determined by differences in the genotype of each parasite strain. However, until
      recently, finding adequate genetic markers to investigate infectivity or other
      epidemiological characteristics of a transmission area proved difficult. Several
      studies have been conducted to evaluate the genetic variability of S. mansoni,
      using different techniques. Intraspecific variability was observed in
      morphological characters, isoenzyme studies, mtDNA, ribosomal gene probes, random
      amplification of polymorphic DNA (RAPD) and microsatellites. The sequencing of
      the S. mansoni genome was the most important achievement concerning genetic
      approaches to the study of this parasite and may improve the development of
      drugs, vaccines and diagnostics of schistosomiasis. The knowledge of the genetic
      structure of schistosome populations in relation to epidemiological data and host
      variability is essential for the understanding of the epidemiology of the disease
      and the design of control strategies.

PMID- 18831956
TI  - A secondary assay for ceramide kinase inhibitors based on cell growth inhibition
      by short-chain ceramides.
AB  - We recently reported that ectopic expression of ceramide kinase (CerK) in various
      cell lines increases their sensitivity to cell death induced by the exogenous
      addition of short-chain (e.g., C2) ceramides (Cer). Here we show that this higher
      sensitivity results from CerK catalytic activity and production of C2-ceramide 1
      phosphate (C2-C1P). If CerK activity is inhibited by the potent inhibitor NVP
      231, C2-C1P is not produced and viability returns to control levels. The EC(50)
      of NVP-231 in this assay is in the low nanomolar range, consistent with the
      IC(50) determined in activity assays in vitro using purified CerK. NVP-995, a
      structurally related but inactive compound, does not protect against C2-Cer
      induced cell death. This assay is robust and easy to implement and scale up,
      thereby providing a valuable secondary screen assay for CerK inhibitors.

PMID- 18831957
TI  - Reduction of DNA contamination in RNA samples for reverse transcription
      polymerase chain reaction using selective precipitation by compaction agents.
AB  - An important problem in measurement of messenger RNA (mRNA) levels by reverse
      transcription-polymerase chain reaction (RT-PCR) is DNA contamination, which can
      produce artifactually increased mRNA concentration. Current methods to eliminate
      contaminating DNA can compromise the integrity of the RNA, are time-consuming,
      and/or are hazardous. We present a rapid, nuclease-free, and cost-effective
      method of eliminating contaminating DNA in RNA samples using selective
      precipitation by compaction agents. Compaction agents are cationic molecules that
      bind to double-stranded nucleic acids, driven by electrostatic interactions and
      steric complementarity. The effectiveness and DNA selectivity of six compaction
      agents were investigated: trivalent spermidine, Triquat A, and Triquat 7;
      tetravalent spermine and Quatro-quat; and hexavalent Quatro-diquat. Effectiveness
      was measured initially by supernatant UV absorbance after precipitation of salmon
      sperm DNA. Effectiveness and selectivity were then investigated using differences
      in RT-PCR C(t) values with synthetic mixtures of human genomic DNA and total RNA
      and with total RNA isolated from cells. With 500 microM spermidine or Triquat A,
      the supernatant DNA could not be detected up to 40 cycles of PCR (C(t)12.6),
      whereas the C(t) for the mRNA was increased by only five cycles. Therefore,
      spermidine and Triquat A each show strong DNA selectivity and could be used to
      eliminate contaminating DNA in measurements of mRNA.

PMID- 18831958
TI  - Calculating reaction rate constants and estimating the efficacy of selective
      enzyme inhibitors.
AB  - The dynamic steady state of a pair of forward and backward enzymatic reactions is
      dependent on the balance between the enzymes catalyzing the reactions. By
      selectively inhibiting one or more of the enzymes involved, this balance is
      shifted into a new steady state, making it possible to calculate the reaction
      rate constants after measurement of the reactants. Ideally, the inhibitors should
      completely eliminate either reaction, but this is often not the case. Here we
      present and discuss a method for calculating the reaction rate constants and,
      thus, for evaluating the efficacy of one or more inhibitors when introduced to a
      forward-backward pair of enzymatic reactions.

PMID- 18831959
TI  - Trifluoroethanol increases albumin's susceptibility to chemical modification.
AB  - Acrolein-dependent chemical modification is implicated in the etiology of
      postoperative cognitive dysfunction (POCD). We examined this process further
      using human serum albumin (HSA), which is a target of acrolein modification and
      contains anesthetic binding sites. We tested whether trifluoroethanol (TFE),
      which mimics inhaled anesthetics, affects the susceptibility of HSA to
      modification by acrolein. We observed that acrolein promoted the formation of
      fluorescent adducts. TFE (10%) increased the amount of acrolein-HSA adducts. TFE
      (40%) caused a 5-fold increase in adduct formation. Acrolein also increased
      tryptophan anisotropy of HSA, which was further increased by TFE (10%). Acrolein
      induced protein cross-linking was also increased in the presence of TFE (40%).
      These observations suggest that TFE promotes acrolein-induced modification of
      HSA, supporting a putative mechanism for POCD.

PMID- 18831960
TI  - Interaction of alkylphospholipid liposomes with MT-3 breast-cancer cells depends
      critically on cholesterol concentration.
AB  - We have investigated interaction of alkyphospholipid (APL) liposomes consisting
      of 1,1-dimethylpiperidin-1-ium-4-yl) octadecyl phosphate (OPP) and different
      concentrations of cholesterol (CH) with human MT-3 breast-cancer cells using
      electron paramagnetic resonance method (EPR) with advanced characterization of
      EPR spectra of spin labeled liposome membranes. After incubation of OPP liposomes
      with MT-3 cells, a reduction of liposome entrapped, water soluble spin-probe
      tempocholine (ASL) was observed, indicating that ASL is released from liposomes
      and is reduced by oxy-redoxy systems inside the cells. This process is fast if
      cholesterol content in the bilayer was 29 or 45 mol%, whereas at 56 mol%
      cholesterol the process is almost stopped. The rate of spin-probe reduction in
      first 10 min after incubation with cells is even faster as for the free ASL,
      indicating that liposomes with low amount of cholesterol accelerate penetration
      of ASL into the cells. A faster release of hydrophilic material from liposomes
      with low cholesterol content coincides with the presence of domains with highly
      disordered alkyl chain motion that disappears at 50 mol% of cholesterol. We
      propose that these highly fluid domains are responsible for interaction of OPP
      liposomes with cells and fast release of the entrapped material into the cells.
      These results suggest that micelles are not the only reason for cytotoxic effect
      of OPP liposome formulations, as it was suggested before. OPP in liposomes,
      containing 45 mol% cholesterol or less, also contributes to the cytotoxic effect,
      due to their fast interaction with breast-cancer cells.

PMID- 18831961
TI  - Identification of antibody responses to the serotype-nonspecific molecular
      species of glycopeptidolipids in Mycobacterium avium infection.
AB  - Glycopeptidolipids (GPLs) comprise a major surface glycolipid of Mycobacterium
      avium complex (MAC), and their unique oligosaccharide extensions are known to
      define MAC serotypes. Beside the mature form of "serotype-specific" GPLs
      (ssGPLs), those that share the backbone structure but lack the oligosaccharide
      extensions exist as abundantly in all MAC serotypes, but the presumption was that
      antibody responses might not be directed to these "serotype-nonspecific" GPLs
      (nsGPLs) due to the lack of the sugar chain epitope. Here, we show that IgG
      responses to nsGPLs indeed occur in MAC-infected guinea pigs. The pool of anti
      nsGPL antibodies was distinct from that of anti-ssGPL antibodies in terms of
      requirements for the oligosaccharide and acetylation for their target
      recognition. Because nsGPLs are shared in virtually all MAC strains, but totally
      absent in Mycobacterium tuberculosis, this study suggests that detecting serum
      anti-nsGPL antibodies can potentially be useful for differential diagnosis of MAC
      infection and tuberculosis.

PMID- 18831962
TI  - Changes in arginase isoenzymes pattern in human hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is one of the most common tumors worldwide
      affecting preferentially patients with liver cirrhosis. The studies were
      performed on tissues obtained during surgery from 50 patients with HCC, 40 with
      liver cirrhosis and 40 control livers. It was found that arginase activity in HCC
      was nearly 5- and 15-fold lower than in cirrhotic and normal livers,
      respectively. Isoenzymes AI (so-called liver-type arginase) and AII (extrahepatic
      arginase) were identified by Western blotting in all studied tissues, however the
      amount of AI, as well as the expression of AI-mRNA were lower in HCC, in
      comparison with normal liver, and those of AII were significantly higher. Since
      HCC is arginine-dependent, and arginine is essential for cells growth, the
      decrease of AI may preserve this amino acid within tumor cells. Concurrently, the
      rise of AII can increase the level of polyamines, compounds crucial for cells
      proliferation. Thus, both arginase isoenzymes seem to participate in liver
      cancerogenesis.

PMID- 18831963
TI  - Up-regulation of semaphorin 3A in human corneal fibroblasts by epidermal growth
      factor released from cocultured human corneal epithelial cells.
AB  - Semaphorins are a family of glycoproteins that play an important role in
      repulsive axon guidance during embryogenesis. We have now investigated the effect
      of corneal epithelial cells on the expression of Sema3A in corneal fibroblasts
      with the use of a coculture system in which the two cell types are separated by a
      collagen vitrigel membrane. Reverse transcription-polymerase chain reaction and
      immunoblot analyses revealed that the presence of immortalized human corneal
      epithelial (HCE) cells increased the expression of Sema3A in human corneal
      fibroblasts at both the mRNA and protein levels. This effect of HCE cells was
      mimicked by recombinant human epidermal growth factor (EGF) in a concentration-
      and time-dependent manner. An inhibitor of the tyrosine kinase activity of the
      EGF receptor, PD153035, blocked the EGF-induced up-regulation of both Sema3A mRNA
      and protein in corneal fibroblasts. Depletion of EGF in HCE cells by RNA
      interference largely abolished the effect of these cells on Sema3A expression in
      corneal fibroblasts. These findings indicate that EGF released from corneal
      epithelial cells up-regulates the expression of Sema3A in corneal fibroblasts.
      This effect of EGF may play an important role in maintenance of corneal structure
      and repair of corneal damage.

PMID- 18831964
TI  - LY294002 inhibits leukemia cell invasion and migration through early growth
      response gene 1 induction independent of phosphatidylinositol 3-kinase-Akt
      pathway.
AB  - LY294002 (LY29) is a commonly used pharmacologic inhibitor of the
      phosphatidylinositol 3-kinase (PI3K) and has shown antitumorigenic effect both in
      vivo and in vitro. Both LY29 and its inactive analogue, LY303511 (LY30),
      significantly up-regulated early growth response gene 1 (Egr-1) expression in HL
      60 leukemic cells. However, wortmannin, another commonly used PI3K inhibitor, was
      not able to induce Egr-1 at the dose that completely blocked Akt phosphorylation.
      LY29 markedly decreased the invasive cells number through Matrigel and human
      umbilical vein endothelial cells (HUVECs) compared with the controls. Moreover,
      the inhibitory effects could be significantly abolished by Egr-1 gene silencing
      with siRNA technology. Our results indicated for the first time that LY29 could
      suppress leukemia cell invasion and migration at least in part through up
      regulation of Egr-1, independent of its PI3K-Akt inhibitory activity. These data
      provide a novel explanation for the anticancer properties of LY29 in leukemias.

PMID- 18831965
TI  - A novel thermophilic lysozyme from bacteriophage phiIN93.
AB  - The lysozyme of bacteriophage phiIN93 was purified to apparent homogeneity with
      Carboxymethyl Sepharose and Hydroxyapatie columns from lysates of the phage grown
      on Thermus aquaticus TZ2. The enzyme is a single polypeptide chain with a
      molecular weight of 33,000. From the determined N-terminal amio acids of the
      enzyme, the locus of the gene was specified on a phiIN93 genome. The enzyme was
      not similar to egg white lysozyme, T4 phage lysozyme, or lambda phage lysozyme.
      The enzyme, phiIN93 lysozyme, was found to be a novel type of thermophilic
      lysozyme, which lyses specifically Thermus sp. cells, and exhibited conspicuous
      thermal stability at 95 degrees C for 1h in the presence of beta-mercaptoethanol.

PMID- 18831966
TI  - Possible role of an ischemic preconditioning-like response mechanism in K(ATP)
      channel opener-mediated protection against streptozotocin-induced suppression of
      rat pancreatic islet function.
AB  - Potassium channel openers (KCOs) decrease insulin secretion from beta-cells. Some
      KCOs also protect against damage to beta-cell function and type 1 diabetes in
      animal models. Previously we have found that the KCO NNC 55-0118 counteracted
      islet cell dysfunction, and this was associated with a lowering of the
      mitochondrial membrane potential (Deltapsi). Presently we aimed to explore
      whether inhibition of insulin secretion per se or rather inhibition of
      mitochondrial function correlates to counteraction of beta-cell suppression. For
      this we used two novel KCOs (NNC 55-0321 and NNC 55-0462), which at certain
      concentrations have different actions regarding insulin secretion and the
      Deltapsi, with NNC 55-0321 being a potent inhibitor of Deltapsi and NNC 55-0462
      being a potent inhibitor of insulin secretion. At 10 microM NNC 55-0321, but not
      with NNC 55-0462, the islet ATP content and ATP/ADP ratio was acutely decreased.
      This was accompanied by a complete protection against streptozotocin-induced
      suppression of islet insulin secretion using the former KCO. In cardiac research
      KCOs have been used to induce an ischemic preconditioning (IPC) response. In line
      with an IPC-like mechanism we found that NNC 55-0321 induced an initial free
      oxygen radical formation, PKC-epsilon isoform activation and a subsequent
      phosphorylation of the survival promoting factor Akt. Thus, KCOs may elicit
      mitochondrial events that resemble classical IPC seen in cardiomyocytes, and this
      could explain the enhanced islet cell function observed. KCOs with this property
      may be particularly interesting compounds to study as a rescue therapy during
      acute episodes of beta-cell suppression/destruction.

PMID- 18831967
TI  - Keeping an eye on retinoic acid signaling during eye development.
AB  - Retinoic acid is a metabolic derivative of vitamin A that plays an essential
      function in cell-cell signaling by serving as a ligand for nuclear receptors that
      directly regulate gene expression. The final step in the conversion of retinol to
      retinoic acid is carried out by three retinaldehyde dehydrogenases encoded by
      Raldh1 (Aldh1a1), Raldh2 (Aldh1a2), and Raldh3 (Aldh1a3). Mouse Raldh gene
      knockout studies have been instrumental in understanding the mechanism of
      retinoic acid action during eye development. Retinoic acid signaling in the
      developing eye is particularly complex as all three Raldh genes contribute to
      retinoic acid synthesis in non-overlapping locations. During optic cup formation
      Raldh2 is first expressed transiently in perioptic mesenchyme, then later Raldh1
      and Raldh3 expression begins in the dorsal and ventral retina, respectively, and
      these sources of retinoic acid are maintained in the fetus. Retinoic acid is not
      required for dorsoventral patterning of the retina as originally thought, but it
      is required for morphogenetic movements that form the optic cup, ventral retina,
      cornea, and eyelids. These findings will help guide future studies designed to
      identify retinoic acid target genes during eye organogenesis.

PMID- 18831969
TI  - Klumpfuss is involved in the determination of sensory organ precursors in
      Drosophila.
AB  - The neural precursor cells (sensory organ precursor cell (SOP)) of the external
      sense organs of Drosophila melanogaster arise from proneural clusters, which are
      defined through the expression pattern of proneural genes such as the genes of
      the achaete-scute complex (AS-C). The activities of these genes enable each cell
      within a cluster to become the SOP. A selection process mediated by the Notch
      signalling pathway and Extramacrochaetae selects a defined number of cells within
      the proneural cluster to realise the SOP fate, while it redirects the rest to the
      epidermoblast fate. Here we report a new function required for SOP determination
      mediated by the zinc finger transcription factor Klumpfuss (Klu). Klu
      participates in a novel mechanism that appears to regulate the expression as well
      as the activity of the proneural proteins. Our analysis indicates that Klu is a
      repressor of transcription, which acts via a double-negative loop to promote SOP
      formation: it suppresses the expression of an unidentified antagonist of
      proneural activity. We present a detailed structure function analysis that
      identifies functionally important domains within Klu.

PMID- 18831968
TI  - Hindbrain-derived Wnt and Fgf signals cooperate to specify the otic placode in
      Xenopus.
AB  - Induction of the otic placode, the rudiment of the inner ear, is believed to
      depend on signals derived from surrounding tissues, the head mesoderm and the
      prospective hindbrain. Here we report the first attempt to define the specific
      contribution of the neuroectoderm to this inductive process in Xenopus. To this
      end we tested the ability of segments of the neural plate (NP), isolated from
      different axial levels, to induce the otic marker Pax8 when recombined with
      blastula stage animal caps. We found that one single domain of the NP,
      corresponding to the prospective anterior hindbrain, had Pax8-inducing activity
      in this assay. Surprisingly, more than half of these recombinants formed otic
      vesicle-like structures. Lineage tracing experiments indicate that these vesicle
      like structures are entirely derived from the animal cap and express several pan
      otic markers. Pax8 activation in these recombinants requires active Fgf and
      canonical Wnt signaling, as interference with either pathway blocks Pax8
      induction. Furthermore, we demonstrate that Fgf and canonical Wnt signaling
      cooperate to activate Pax8 expression in isolated animal caps. We propose that in
      the absence of mesoderm cues the combined activity of hindbrain-derived Wnt and
      Fgf signals specifies the otic placode in Xenopus, and promotes its morphogenesis
      into an otocyst.

PMID- 18831970
TI  - A therapeutic dose of zolpidem has limited abuse-like effects in drug-naive
      females: a pilot study.
AB  - Zolpidem has abuse potential, particularly among individuals with histories of
      drug abuse. This double-blind, placebo-controlled, cross over pilot study
      investigated the subjective effects of zolpidem (10 mg) in drug-naive females.
      Over the course of a 5-h period vital signs were monitored and a series of
      computerized questionnaires was administered. Results indicate that zolpidem
      engendered subjective effects characteristic of hypnotic drugs, but reduced
      ratings of drug liking, willing to take again, and willing to pay for, relative
      to placebo. Thus, a therapeutic dose of zolpidem may have limited potential for
      misuse among females who have no experience with drugs of abuse.

PMID- 18831971
TI  - Characterization of aripiprazole partial agonist activity at human dopamine D3
      receptors.
AB  - Aripiprazole is the first dopamine D2/D3 receptor partial agonist approved for
      use in the treatment of psychiatric disorders, including schizophrenia, bipolar
      disorder, and unipolar depression in the US. To explore the functional activity
      of aripiprazole at dopamine D3 receptors, we established Chinese hamster ovary
      (CHO) cell lines stably expressing high and low densities of Ser-9 and Gly-9
      variants of human dopamine D3 receptors and compared aripiprazole's dopamine D3
      pharmacological properties with other marketed and non-approved dopamine D3
      receptor modulating agents on inhibition of forskolin-stimulated cAMP
      accumulation. Maximal cell responses for dopamine were dependent on receptor
      expression levels, and all cells had similar potency for dopamine responses.
      Aripiprazole, terguride, bifeprunox, OPC-4392 (7-(3-[4-(2,3
      dimethylphenyl)piperazinyl]propoxy)-2(1H)-quinolinone), (-)-3-PPP ((-)-3-(3
      hydroxyphenyl)-N-n-propylpiperidine), SDZ 208-912 (N-[(8 alpha)-2-chloro-6
      methylergolin-8-yl]-2,2-dimethylpropanamide), BP897 (N-[4-[4-(2-Methoxyphenyl)-1
      piperazinyl]butyl]naphthalene-2-carboxamide) and GR103691 (4'-Acetyl-N-[4-[4-(2
      methoxyphenyl)piperazin-1-yl]butyl]biphenyl-4-carboxamide) behaved as partial
      agonists. Aripiprazole's intrinsic activity was similar to that of BP897 and
      GR103691, lower than that of terguride, bifeprunox, OPC-4392, and (-)-3-PPP, and
      higher than that of SDZ 208-912. The Gly-9 variant did not differ from the Ser-9
      variant with respect to those agonist potencies and intrinsic activities. These
      compounds blocked the action of dopamine with a maximum effect equal to that of
      each compound alone. ACR16 (4-(3-Methanesulfonyl-phenyl)-1-propyl-piperidine),
      quetiapine, clozapine, olanzapine, ziprasidone, risperidone, and haloperidol
      acted as antagonists. Aripiprazole's unique activity at dopamine D3 receptors may
      translate into clinically relevant outcomes in patients with a variety of
      neuropsychiatric disorders.

PMID- 18831972
TI  - A low nicotine concentration augments vesicle motion and exocytosis triggered by
      K(+) depolarisation of chromaffin cells.
AB  - Tobacco smokers have an increased risk of cardiovascular disease; this is likely
      associated to an enhanced catecholamine release by circulating nicotine. Here, we
      have explored how low concentrations of nicotine in the range of those found in
      the blood of tobacco smokers, might affect the release of catecholamines in
      bovine chromaffin cells. We have combined patch-clamp and Ca(2+) imaging
      techniques to study cell excitability, cytosolic Ca(2+) transients, vesicle
      movement, and secretory responses. We found that low concentrations of nicotine
      (1.5-3 microM) did not enhance catecholamine release by themselves. However, they
      drastically augmented the catecholamine release response triggered by a
      supramaximal K(+) depolarising pulse. Furthermore, low nicotine concentrations
      caused slight depolarisation with superimposed action potentials, a transient
      elevation of [Ca(2+)](c) and augmented Ca(2+)-dependent vesicle motion underneath
      the plasmalemma. We suggest that low nicotine concentrations overload the
      secretory machinery with secretory vesicles, which cause chromaffin cells to
      respond with an exaggerated adrenaline release into the circulation during
      stress. This might contribute to the higher cardiovascular risk of tobacco
      smokers.

PMID- 18831973
TI  - Activation of high conductance Ca(2+)-activated K(+) channels by sodium
      tanshinoneII-A sulfonate (DS-201) in porcine coronary artery smooth muscle cells.
AB  - High conductance Ca(2+) activated K(+) channels (BK(Ca)) in vascular smooth
      muscles play important roles in controlling the vascular tone by determining the
      level of membrane potential and Ca(2+) influx through voltage gated Ca(2+)
      channels. Agents that alter the activity of Ca(2+) channels or BK(Ca) thus affect
      the vascular tone in both physiological and pathological conditions. Danshen, the
      dried root of Salvia miltiorrhiza, is a commonly used traditional Chinese
      medicine and is widely used as an effective remedy for cardiovascular and
      cerebral vascular diseases partly by its vasodilatation. Sodium tanshinoneII-A
      sulfonate (DS-201) is a water-soluble derivative of Tanshinone IIA, the main
      active component of Danshen. The purpose of this study was to explore possible
      mechanisms of vasodilative effects of DS-201 using porcine coronary artery smooth
      muscle. DS-201 induced relaxation of the coronary smooth muscle which had been
      contracted with 30 mM KCl, and the relaxation was inhibited by 100 nM iberiotoxin
      (IbTX), a specific BK(Ca) channel blocker. Using perforated whole-cell recordings
      and single channel recordings, effects of DS-201 on BK(Ca) were examined. The
      results showed that DS-201 activated BK(Ca). Extracellular application of DS-201
      at 40, 80 microM under the whole-cell configuration induced increases of the
      BK(Ca) macroscopic currents by 43.6%, 42.1% respectively, and the spontaneous
      transient outward K(+) currents (STOCs) by 48.7%, 47.4% respectively. In inside
      out patches, bath application of 20-150 muM of DS-201 activated BK(Ca) by 5.4
      173.2 fold. These results indicate that the vasodilatation by DS-201 is related
      to activation of BK(Ca).

PMID- 18831974
TI  - Mitochondria and L-lactate metabolism.
AB  - Although mitochondria have been the object of intensive study over many decades,
      some aspects of their metabolism remain to be fully elucidated, including the L
      lactate metabolism. We review here the novel insights arisen from investigations
      on L-lactate metabolism in mammalian, plant and yeast mitochondria. The presence
      of L-lactate dehydrogenases inside mitochondria, where L-lactate enters in a
      carrier-mediated fashion, suggests that mitochondria play an important role in L
      lactate metabolism. Functional studies have demonstrated the occurrence of
      several L-lactate carriers. Moreover, immunological investigations have proven
      the existence of monocarboxylate translocator isoforms in mitochondria.

PMID- 18831975
TI  - Stable expression of a GFP-BSD fusion protein in Babesia bovis merozoites.
AB  - Transfection has been a valuable technique for elucidating gene function in many
      pathogens. While transient transfection of Babesia spp. has been reported
      previously, stable integration of exogenous genes in Babesia has proven
      difficult. In this study, a plasmid was designed to target integration of a gfp
      bsd gene into the Babesia bovis ef-1alpha locus. Babesia bovis-infected
      erythrocytes of the biologically cloned Mo7 strain were transfected by
      electroporation with either circular or linear plasmids and selected in cultures
      with varying amounts of blasticidin 24h after electroporation. Several
      blasticidin-resistant B. bovis transfected cell lines emerged at different rates,
      ranging from 5 to 26 days after the start of selection. One transfected parasite
      line (1-2-124) was selected for further analysis based on a rapid growth rate and
      bright GFP fluorescence in the presence of a lethal concentration of blasticidin.
      Continued expression of the gfp-bsd fusion gene was confirmed by reverse
      transcriptase-PCR, Western blot analysis and fluorescence microscopy for longer
      than 9 months after electroporation. No plasmid or episomal DNA could be detected
      in this line, and plasmid recovery in Escherichia coli was unsuccessful. Southern
      blot results and sequencing of PCR amplicons flanking the putative insertion site
      are consistent with integration of at least one gfp-bsd cassette into the
      targeted ef-1alpha locus in the transfected parasite line. Overall the results
      demonstrate, we believe for the first time, chromosomal integration and stable
      expression of a foreign gene in B. bovis. With the availability of the B. bovis
      genome, targeted stable transfection will provide a means to determine the role
      of specific genes in the biology, clinical disease and immunity of B. bovis, one
      of the three major tick-borne parasites that limit global livestock production.

PMID- 18831976
TI  - Genetic analysis of the cytoplasmic domain of the PfRh2b merozoite invasion
      protein of Plasmodium falciparum.
AB  - Apicomplexan parasites employ multiple adhesive ligands for recognition and entry
      into host cells. The Duffy binding-like (DBL) and the reticulocyte binding
      protein-like (RBL) families are central to the invasion of erythrocytes by the
      malaria parasite. These type-1 transmembrane proteins are composed of large
      ectodomains and small conserved cytoplasmic tail domains. The cytoplasmic tail
      domain of the micronemal DBL protein EBA-175 is required for a functional ligand
      receptor interaction, but not for correct trafficking and localisation. Here we
      focus on the cytoplasmic tail domain of the rhoptry-localised Plasmodium
      falciparum RBL PfRh2b. We have identified a conserved sequence of six amino
      acids, enriched in acidic residues, in the cytoplasmic tail domains of RBL
      proteins from Plasmodium spp. Genetic analyses reveal that the entire cytoplasmic
      tail and the conserved motif within the cytoplasmic tail are indispensable for
      invasion P. falciparum. Site-directed mutagenesis of the conserved moiety reveals
      that changes in the order of the amino acids of the conserved moiety, but not the
      charge of the sequence, can be tolerated. Shuffling of the motif has no effect on
      either invasion phenotype or PfRh2b expression and trafficking. Although the
      PfRh2b gene can be readily disrupted, our results suggest that modification of
      the PfRh2b cytoplasmic tail results in strong dominant negative activity,
      highlighting important differences between the PfRh2b and EBA-175 invasion
      ligands.

PMID- 18831977
TI  - Female mating receptivity after injection of male-derived extracts in
      Callosobruchus maculatus.
AB  - The effects of male-derived extracts on female receptivity were investigated in
      Callosobruchus maculatus (Coleoptera: Bruchidae). Injection of aqueous extracts
      of the male reproductive tract into the abdomen of females reduced receptivity.
      Aqueous extracts of male reproductive tracts were divided to three molecular
      weight (MW) fractions by ultrafiltration: Fractions: (I) MW<3 kDa, (II) 3-14 kDa,
      and (III)>14 kDa. Fraction II reduced female receptivity from 3h after injection,
      and Fraction III reduced female receptivity from 2 days after injection. On the
      other hand, no effect on receptivity was found for Fraction I. Furthermore, male
      reproductive tract organs were divided into accessory gland, testis, and seminal
      vesicle including the ejaculatory duct. Aqueous extracts of the seminal vesicle
      reduced receptivity of females immediately following injection, while aqueous
      extracts of the accessory gland reduced receptivity at the second day. The
      results suggest that the components of Fraction II existed in the seminal
      vesicle, and those of Fraction III in the accessory gland. The results of the
      present and the previous studies in Callosobruchus chinensis, a species closely
      related to C. maculatus, were compared and are discussed from the viewpoint of
      the significance of ejaculation in the two species.

PMID- 18831978
TI  - Genetic diversity among isolates of Paenibacillus larvae from Austria.
AB  - Genetic diversity of 214 Paenibacillus larvae strains from Austria was studied.
      Genotyping of isolates was performed by polymerase chain reaction (PCR) with
      primers corresponding to enterobacterial repetitive intergenic consensus (ERIC),
      BOX repetitive and extragenic palindromic (REP) elements (collectively known as
      rep-PCR) using ERIC primers, BOX A1R and MBO REP1 primers. Using ERIC-PCR
      technique two genotypes could be differentiated (ERIC I and II), whereas using
      combined typing by BOX- and REP-PCR, five different genotypes were detected (ab,
      aB, Ab, AB and alphab). Genotypes aB and alphab are new and have not been
      reported in other studies using the same techniques.

PMID- 18831979
TI  - Who gains or who loses weight? Psychosocial factors among first-year university
      students.
AB  - Self-reported weight changes over 7 months and their relation to psychosocial
      characteristics (self-esteem, depression, social support, perceived stress and
      transition perception) and eating attitudes and behaviors (restrained eating and
      Eating Disorder Inventory subscales [EDI]) were assessed in first-year male and
      female students at six Canadian universities (N=2753). Results showed small but
      significant weight increases over time in males and females (M=1.5 kg). Males who
      lost weight versus those who gained reported greater negative well-being and more
      negative feelings about university transition. Females who either lost or gained
      weight had higher initial restraint and EDI scores than did weight maintainers.
      At 3 months, total EDI and body dissatisfaction increased in female weight
      gainers compared to weight losers, plus greater drive for thinness compared to
      weight maintainers. Thus, males distressed at the transition from high school to
      university appear more likely to lose weight while well-adjusted males are more
      likely to gain weight. For females, however, weight gain is associated with more
      negative well-being and preoccupations with weight and eating.

PMID- 18831980
TI  - Increased SULT1E1 activity in HepG2 hepatocytes decreases growth hormone
      stimulation of STAT5b phosphorylation.
AB  - Mouse models of cystic fibrosis (CF) display increased sulfotransferase 1E1
      (SULT1E1) activity in hepatocytes of cystic fibrosis transmembrane receptor
      (CFTR)-deficient animals. SULT1E1 is responsible for the sulfation and
      inactivation of beta-estradiol (E2) at physiological concentrations. IGF-1
      message levels in CFTR(-/-) mouse livers were positively correlated with body
      weight and negatively correlated with SULT1E1 activity. Growth hormone (GH) is
      important in the regulation of hepatic IGF-1 expression indicating that E2 levels
      are involved with GH signaling in hepatocytes. To investigate the effects of E2
      and SULT1E1 activity on GH signal transduction in human hepatocytes, SULT1E1 was
      stably expressed in HepG2 cells. Effects of increased E2 sulfation on the GH
      signaling pathway and E2-regulated gene expression were examined. Pretreatment of
      HepG2 cells with 10nM E2 prior to GH stimulation increased STAT5b phosphorylation
      and IGF-1 expression. In SULT1E1-transfected HepG2 cells, GH-stimulated STAT5b
      phosphorylation was significantly decreased. E2 treatment had no effect on STAT5b
      phosphorylation in the absence of GH stimulation. E2 also had no effect on Jak-2
      phosphorylation. E2 has an apparent rapid action on increasing GH-stimulated
      STAT5b phosphorylation that was not attenuated by the estrogen receptor
      antagonist, ICI 182,780. Physiological levels of E2 in HepG2 cells increase GH
      stimulation of IGF-1 production apparently through increased phosphorylated
      STAT5b levels and transcriptional activation of the IGF-1 gene. The enhanced
      SULT1E1 activity may have a role in inhibiting GH-stimulated STAT5b
      phosphorylation and IGF-1 synthesis via the sulfation and inactivation of E2.

PMID- 18831981
TI  - A model for venom-induced consumptive coagulopathy in snake bite.
AB  - Many snake venoms contain procoagulant toxins that activate the coagulation
      cascade and cause venom-induced consumptive coagulopathy (VICC). We developed a
      semi-mechanistic model of the clotting cascade in order to explore the effects of
      the procoagulant toxin from taipan venom on this system as well as the effects of
      antivenom. Simulations of the time course in the change of clotting factors were
      compared to data collected from taipan envenomed patients. The model accurately
      predicted the observed concentration of clotting factors over time following
      taipan envenomation. Investigations from the model indicated that the upper limit
      of the half-life of the procoagulant toxin was 1h. Simulations from the model
      also suggest that antivenom for Australasian elapids has negligible effect on
      reducing the recovery time of the coagulation profile unless administered almost
      immediately after envenomation. The model has generality to be expanded to
      describe the effects of other venoms and drugs on the clotting cascade.

PMID- 18831982
TI  - The three-dimensional structure of bothropasin, the main hemorrhagic factor from
      Bothrops jararaca venom: insights for a new classification of snake venom
      metalloprotease subgroups.
AB  - Bothropasin is a 48kDa hemorrhagic PIII snake venom metalloprotease (SVMP)
      isolated from Bothrops jararaca, containing disintegrin/cysteine-rich adhesive
      domains. Here we present the crystal structure of bothropasin complexed with the
      inhibitor POL647. The catalytic domain consists of a scaffold of two subdomains
      organized similarly to those described for other SVMPs, including the zinc and
      calcium-binding sites. The free cysteine residue Cys189 is located within a
      hydrophobic core and it is not available for disulfide bonding or other
      interactions. There is no identifiable secondary structure for the disintegrin
      domain, but instead it is composed mostly of loops stabilized by seven disulfide
      bonds and by two calcium ions. The ECD region is in a loop and is structurally
      related to the RGD region of RGD disintegrins, which are derived from PII SVMPs.
      The ECD motif is stabilized by the Cys277-Cys310 disulfide bond (between the
      disintegrin and cysteine-rich domains) and by one calcium ion. The side chain of
      Glu276 of the ECD motif is exposed to solvent and free to make interactions. In
      bothropasin, the HVR (hyper-variable region) described for other PIII SVMPs in
      the cysteine-rich domain, presents a well-conserved sequence with respect to
      several other PIII members from different species. We propose that this subset be
      referred to as PIII-HCR (highly conserved region) SVMPs. The differences in the
      disintegrin-like, cysteine-rich or disintegrin-like cysteine-rich domains may be
      involved in selecting target binding, which in turn could generate substrate
      diversity or specificity for the catalytic domain.

PMID- 18831983
TI  - The effect of aging on contour integration.
AB  - Perception of global patterns requires the integration of local orientation
      information across space. The present study examined whether this integration
      ability declines in older age. We measured contrast thresholds for discriminating
      the global orientation of a "C" shaped contour against a blank background in
      younger and older subjects. Performance of younger subjects improved when the
      elements composing the "C" were aligned along the contour path, as opposed to
      being orthogonal to it or of mixed orientations. However, older subjects'
      performance was not affected by the orientation of the local elements. This
      indicates an age-related decline in contour integration.

PMID- 18831984
TI  - Influence of target and distractor contrast on the remote distractor effect.
AB  - In the absence of distractors, saccadic latencies are influenced by target
      characteristics such as contrast. The same characteristics were expected to
      influence the remote distractor effect (RDE) when varied in the distractor. We
      conducted three experiments in which we varied target and distractor contrast
      orthogonally. The results show that the RDE is not so much modulated by
      distractor contrast per se. Rather it strongly depended on the overall saccadic
      latencies afforded by the target: typically, shorter latencies resulted in
      stronger RDEs. We argue that average saccadic latencies to a target determine
      whether distractor-related activity temporally coincides with target-related
      activity. The temporal overlap is necessary for the respective neuronal signals
      to inhibit each other, thus evoking the RDE.

PMID- 18831985
TI  - Texture modulation detection by probability summation among orientation-selective
      and isotropic mechanisms.
AB  - Substantial evidence has accumulated for the notion that modulations of second
      order properties in the visual scene are processed by mechanisms which detect
      contrast variations within narrow orientation/spatial frequency channels. It has
      also been suggested that mechanisms exist which detect contrast modulations
      across all orientations. Many naturally occurring texture variations (e.g.,
      modulations in orientation and/or spatial frequency) involve simultaneous
      contrast modulations in multiple channels. Contrasting conclusions have been
      drawn regarding the manner in which the information carried in multiple channels
      is combined. In a series of two experiments it is shown that simultaneous
      contrast modulations in two narrow orientation bands are detected by three
      mechanisms, two of which detect contrast modulations within the modulated bands
      only, the third of which integrates contrast across orientations in order to
      detect modulations of overall contrast. The three mechanisms combine their
      efforts by probability summation.

PMID- 18831986
TI  - Molecular characterization, expression and functional analysis of goldfish
      (Carassius aurutus L.) interferon gamma.
AB  - We report on the characterization and functional analysis of IFNgamma of the
      goldfish. Quantitative analysis indicated the highest expression of goldfish
      IFNgamma in the spleen, with lower expressions in brain, gill, kidney, heart,
      intestine and muscle. An increase in IFNgamma expression was observed in kidney
      leukocytes following stimulation with PHA, PolyI:C and during mixed leukocyte
      reaction. IFNgamma was expressed in different goldfish immune cell populations
      and this expression was upregulated in several of these populations following
      treatment of cells with recombinant goldfish TNFalpha-2. A recombinant form of
      goldfish IFNgamma (rgIFNgamma) was produced and functionally analyzed. The
      rgIFNgamma primed goldfish macrophages and neutrophils for enhanced respiratory
      burst responses and increased the phagocytic and nitric oxide responses of
      macrophages. Furthermore, treatment of goldfish macrophages with rgIFNgamma
      induced increased expression of several proinflammatory genes including TNFalpha
      1, TNFalpha-2, IL-beta-1, IL-beta-2, IL-12-p35, IL-12-p40, RSAD-2 (=viparin),
      CXCL-8 (=IL-8), CCL-1, iNOS A and B and IFNgamma, and decreased the expression of
      TLR-3, while the expression of TGFbeta remained unchanged. Our results indicate
      that IFNgamma is a central proinflammatory cytokine of teleosts.

PMID- 18831987
TI  - Engineered Saccharomyces cerevisiae strain for improved xylose utilization with a
      three-plasmid SUMO yeast expression system.
AB  - A three-plasmid yeast expression system utilizing the portable small ubiquitin
      like modifier (SUMO) vector set combined with the efficient endogenous yeast
      protease Ulp1 was developed for production of large amounts of soluble functional
      protein in Saccharomyces cerevisiae. Each vector has a different selectable
      marker (URA, TRP, or LEU), and the system provides high expression levels of
      three different proteins simultaneously. This system was integrated into the
      protocols on a fully automated plasmid-based robotic platform to screen
      engineered strains of S. cerevisiae for improved growth on xylose. First, a novel
      PCR assembly strategy was used to clone a xylose isomerase (XI) gene into the URA
      selectable SUMO vector and the plasmid was placed into the S. cerevisiae INVSc1
      strain to give the strain designated INVSc1-XI. Second, amino acid scanning
      mutagenesis was used to generate a library of mutagenized genes encoding the
      bioinsecticidal peptide lycotoxin-1 (Lyt-1) and the library was cloned into the
      TRP-selectable SUMO vector and placed into INVSc1-XI to give the strain
      designated INVSc1-XI-Lyt-1. Third, the Yersinia pestis xylulokinase gene was
      cloned into the LEU-selectable SUMO vector and placed into the INVSc1-XI-Lyt-1
      yeast. Yeast strains expressing XI and xylulokinase with or without Lyt-1 showed
      improved growth on xylose compared to INVSc1-XI yeast.

PMID- 18831988
TI  - A method for localizing microelectrode trajectories in the macaque brain using
      MRI.
AB  - Magnetic resonance imaging (MRI) is often used by electrophysiologists to target
      specific brain regions for placement of microelectrodes. However, the
      effectiveness of this technique has been limited by few methods to quantify in
      three dimensions the relative locations of brain structures, recording chambers
      and microelectrode trajectories. Here we present such a method. After surgical
      implantation, recording chambers are fitted with a plastic cylinder that is
      filled with a high-contrast agent to aid in the segmentation of the cylinder from
      brain matter in an MRI volume. The resulting images of the filled cylinder
      correspond to a virtual cylinder that is projected along its long axis - parallel
      to the trajectories of microelectrodes advanced through the recording chamber -
      through the three-dimensional image of the brain. This technique, which does not
      require a stereotaxic coordinate system, can be used to quantify the coverage of
      an implanted recording chamber relative to anatomical landmarks at any depth or
      orientation. We have used this technique in conjunction with Caret [Van Essen DC,
      Drury HA, Dickson J, Harwell J, Hanlon D, Anderson CH. An integrated software
      suite for surface-based analyses of cerebral cortex. J Am Med Inform Assoc
      2001;8:443-59] and AFNI [Cox RW. AFNI: software for analysis and visualization of
      functional magnetic resonance neuroimages. Comput Biomed Res 1996;29:162-73]
      brain-mapping software to successfully localize several regions of macaque
      cortex, including the middle temporal area, the lateral intraparietal area and
      the frontal eye field, and one subcortical structure, the locus coeruleus, for
      electrophysiological recordings.

PMID- 18831989
TI  - A TaqMan real-time RT-PCR assay for selective detection of atypical bovine
      pestiviruses in clinical samples and biological products.
AB  - Novel 'atypical' pestiviruses have been detected recently in biological products,
      e.g. fetal calf serum (FCS) batches, and in cattle infected naturally. Due to
      genetic and antigenic variation in pestiviruses, the current diagnostic assays
      have limitations for the detection of atypical bovine pestiviruses described
      recently. This paper describes a new one-step real-time RT-PCR assay for the
      specific detection of atypical bovine pestiviruses, including D32/00_'HoBi', Brz
      buf 9, CH-KaHo/cont, and Th/04_KhonKaen viruses. The assay detects around 200
      copies of synthetic viral RNA molecules per reaction. Coefficient variation (CV)
      values ranged from 0.13 to 2.11% in three tests performed within 5 weeks, showing
      that this assay is highly reproducible. To evaluate the suitability for specific
      detection and identification of the atypical bovine pestiviruses, the assay was
      evaluated on 46 clinical samples, five batches of FCS and one live Theileria
      annulata vaccine. Five clinical samples and four batches of commercial FCS were
      positive for atypical pestiviruses. This new assay provides a useful tool for
      highly sensitive and specific detection of atypical bovine pestiviruses in
      clinical samples and can be applied in combination with other diagnostic methods
      to ensure that biological products, including FCS and vaccines, are free from
      contamination with pestiviruses.

PMID- 18831990
TI  - Validation of a 2-day water maze protocol in mice.
AB  - We present a 2-day water maze protocol that addresses some of potential confounds
      present in the water maze when using the aged subjects typical of studies of
      neurodegenerative disorders, such as Alzheimer's disease. This protocol is based
      on an initial series of training trials with a visible platform, followed by a
      memory test with a hidden platform 24h later. We validated this procedure using
      aged (15-18m) mice expressing three Alzheimer's disease-related transgenes,
      PS1(M146 V), APP(Swe), and tau(P301L). We also tested these triple transgenic
      mice (3xTG) and age and sex-matched wild-type (WT) in a behavioral battery
      consisting of tests of motor coordination (balance beam), spatial memory (object
      displacement task) visual acuity (novel object recognition task) and locomotor
      activity (open field). 3xTG mice had significantly longer escape latencies in the
      memory trial of the 2-day water maze test than WT and than their own baseline
      performance in the last visible platform trial. In addition, this protocol had
      improved sensitivity compared to a typical probe trial, since no significant
      differences between genotypes were evident in a probe trial conducted 24h after
      the final training trial. The 2-day procedure also resulted in good reliability
      between cohorts, and controlled for non-cognitive factors that can confound water
      maze assessments of memory, such as the significantly lower locomotor activity
      evident in the 3xTG mice. A further benefit of this method is that large numbers
      of animals can be tested in a short time.

PMID- 18831991
TI  - Nicotinic alpha7- or beta2-containing receptor knockout: effects on radial-arm
      maze learning and long-term nicotine consumption in mice.
AB  - Classically, it has been thought that high-affinity nicotinic receptors
      containing beta2 subunits are the most important receptor subtypes for nicotinic
      involvement in cognitive function and nicotine self-administration, while low
      affinity alpha7-containing nicotinic receptors have not been thought to be
      important. In the current study, we found that knockout of either beta2 or alpha7
      subunits caused significant deficits in spatial discrimination in mice. The
      character of the impairment in the two knockouts was different. The beta2
      knockout preferentially impaired cognition in males while the alpha7 caused
      impairment regardless of sex. Both beta2- and alpha7-containing nicotinic
      receptors also are important for nicotine self-administration, also in different
      ways. Most animal model studies of nicotine self-administration are relatively
      short-term whereas the problem of tobacco addiction is considerably longer-term.
      To better model the impact of nicotinic receptor subtypes on nicotine self
      administration over the long-term, we studied the impact of genetic knockout of
      low affinity alpha7 receptors vs. high-affinity beta2-containing nicotinic
      receptors. Mice with knockouts of either of these receptors and their wildtype
      counter parts were given free access to a choice of nicotine-containing and
      nicotine-free solution in their home cages on a continuous basis over a period of
      5 months. During the first few weeks, the beta2-containing nicotinic receptor
      knockout mice showed a significant decrease in nicotine consumption relative to
      wildtype mice, whereas the alpha7 knockout mice did not significantly differ from
      wildtype controls at the beginning of their access to nicotine. Interestingly, in
      the longer-term after the first few weeks of nicotine access, the beta2 knockout
      mice returned to wildtype mouse levels of nicotine consumption, whereas the
      alpha7 knockout mice developed an emergent decrease in nicotine consumption. The
      alpha7 receptor knockout-induced decrease in nicotine consumption persisted for
      the 5-month period of the study. Both alpha7- and beta2-containing nicotinic
      receptors play critical roles in cognitive function and nicotine self
      administration. Regarding cognitive function, beta2-containing receptors are
      important for maintaining normal sex differences in spatial learning and memory,
      whereas alpha7 receptors are important for cognitive function regardless of sex.
      Regarding nicotine self-administration high-affinity beta2-containing nicotinic
      receptors are important for consumption during the initial phase of nicotine
      access, but it is the alpha7 nicotinic receptors that are important for the
      longer-term regulation of nicotine consumption.

PMID- 18831992
TI  - Early cognitive and language skills are linked to resting frontal gamma power
      across the first 3 years.
AB  - High-frequency cortical activity in humans and animals has been linked to a wide
      variety of higher cognitive processes. This research suggests that specific
      changes in neuronal synchrony occur during cognitive processing, distinguished by
      emergence of fast oscillations in the gamma frequency range. To determine whether
      the development of high-frequency brain oscillations can be related to the
      development of cognitive abilities, we studied the power spectra of resting EEG
      in children 16, 24 and 36 months of age. Individual differences in the
      distribution of frontal gamma power during rest were highly correlated with
      concurrent language and cognitive skills at all ages. Gamma power was also
      associated with attention measures; children who were observed as having better
      inhibitory control and more mature attention shifting abilities had higher gamma
      power density functions. We included a group of children with a family history of
      language impairment (FH+) and thus at higher risk for language disorders. FH+
      children, as a group, showed consistently lower gamma over frontal regions than
      the well-matched FH- controls with no such family history (FH-). We suggest that
      the emergence of high-frequency neural synchrony may be critical for cognitive
      and linguistic development, and that children at risk for language impairments
      may lag in this process.

PMID- 18831993
TI  - Detection of vector- and selectable marker-free transgenic maize with a linear
      GFP cassette transformation via the pollen-tube pathway.
AB  - The pollen-tube pathway is feasible to transform vector- and selectable marker
      free linear gene cassettes into plants to address the biosafety issues. However,
      its transformation frequency is low and the screening of selectable marker-free
      transformants by PCR analysis is time-consuming and expensive. In this study, a
      linear GFP cassette (Ubi-GFP-nos) flanked by 25bp T-DNA borders was transformed
      into maize via the pollen-tube pathway. The forepart of each maize ear was
      divided into five segments (segments I-V) at an interval of two rows of kernels.
      The segments that were most likely to contain transgenic kernels were identified
      by monitoring GFP expression in the immature embryos. A total of 21 ears were
      transformed with the linear GFP cassette. Seven out of 19 ears exhibited positive
      GFP expression in the immature embryos. Transgenic kernels were primarily
      identified in segments III and IV. A total of 121 plants derived from kernels
      located within segments III and IV of the remaining two ears were screened by PCR
      analysis. Six plants (4.96%) showed the presence of the GFP cassette. Southern
      blot analysis showed that the transgenic plants had simple integration patterns.
      The identification of transgenic kernels would facilitate PCR screening for
      marker-free transgenic plants.

PMID- 18831994
TI  - A pathogenic picorna-like virus from the endoparasitoid wasp, Pteromalus puparum:
      initial discovery and partial genomic characterization.
AB  - Using electron microscopy, we demonstrated the presence of a novel small RNA
      containing virus in the venom apparatus of an endoparasitic wasp, Pteromalus
      puparum, designated as PpSRV. Morphologically, PpSRV has classical features of
      picorna-like viruses. It caused the development deterioration and tissue
      destruction of P. puparum venom apparatus. The laboratory colony of P. puparum
      was infectious with PpSRV at a low level. Partial genomic sequence analysis
      indicated that PpSRV 3'-proximal genome was characteristically similar to most
      dicistroviruses containing an internal ribosome entry site (IRES) for
      facilitating cap-independent translation and a 3' ORF encoding a structural
      protein with three major capsid polyproteins (28, 31 and 28 kDa) and a minor one
      (9.6 kDa). Phylogenetic evolution analysis of PpSRV structural protein with the
      counterparts of other dicistroviruses exhibited that PpSRV belonged to the
      Cripavirus genus and fell into same clade with Black queen cell virus (BQCV), an
      infectious virus to honey bee, suggesting that PpSRV might be pathogenic to P.
      puparum.

PMID- 18831995
TI  - Understanding skin architecture: a two photon microscopy study.

PMID- 18831996
TI  - Changes in appetite hormone (ghrelin) levels of saliva and serum in acute
      appendicitis cases before and after operation.
AB  - This study was designed to measure the levels of serum and saliva ghrelin
      concentrations before and after surgery in an attempt to clarify whether this
      hormone plays any significant roles in acute appendicitis and cholelithiasis
      patients when compared with healthy controls. Samples were obtained from 20
      patients with appendicitis, 10 patients with cholelithiasis before and after
      operation, and 16 healthy controls. The levels of ghrelin (acylated) were
      measured by means of a RIA assay. The results revealed that preoperative levels
      of ghrelin in saliva and serum were significantly decreased with respect to post
      op in patients undergoing appendectomy, and control levels. This was also the
      case when the preoperative ghrelin concentrations in patients with appendicitis
      were compared with those having choelithiasis. Taken together, decreased ghrelin
      concentration in preoperative appendicitis might be a causative factor for the
      "loss of appetite" observed in an acute inflammatory condition such as acute
      appendicitis. However, further studies are necessary to reveal the exact
      mechanisms behind this observation.

PMID- 18831997
TI  - Measuring affective (liking) and non-affective (expected satiety) determinants of
      portion size and food reward.
AB  - Previously, we have used a 'method of constant stimuli' to quantify the satiety
      that different foods are expected to deliver. Our data indicate that foods differ
      considerably (some are expected to deliver 5-6 times more satiety than others
      [per kcal]). In the present study we explored the relative importance of
      'expected satiety' in decisions about portion size. For eight different snack
      foods, we measured 'ideal' portion size and compared these values with
      corresponding measures of liking, expected satiety, and intention to restrict
      intake. Across participants (N=60), ideal portion size was predicted by both
      liking and expected satiety. Individuals differed in the relative importance of
      expected satiety and liking. In particular, expected satiety was a more important
      predictor in restrained eaters and in individuals with a higher BMI. In this
      study we also included a measure of food reward. For each food, reward was
      inferred from a measure based on cash spend per kcal. Again, food liking and
      expected satiety were both significant predictors. Together, our findings confirm
      the importance of expected satiety and they demonstrate the quantification of
      separate affective and non-affective determinants of food reward and portion
      size.

PMID- 18831998
TI  - A new type of neuron-specific aminopeptidase NAP-2 in rat brain synaptosomes.
AB  - A novel neutral aminopeptidase (NAP-2) was found exclusively in the rat central
      nervous system (CNS). It was separated from the ubiquitous puromycin-sensitive
      aminopeptidase (PSA) and the neuron-specific aminopeptidase (NAP) by an automated
      FPLC-aminopeptidase analyzer. The activity of the neuronal aminopeptidase
      enriched in the synaptosomes is different from NAP and PSA in distribution and
      during brain development. The enzyme was purified 2230-fold to apparent
      homogeneity from rat brain cytosol with 4% recovery by ammonium sulfate
      fractionation, followed by column chromatography successively on Phenyl
      Sepharose, Q-Sepharose, Sephadex G-200, and Mono Q. The single-chain enzyme with
      a molecular mass of 110kDa has an optimal pH of 7.0 and a pI of 5.6. It splits
      beta-naphthylamides of amino acid with aliphatic, polar uncharged, positively
      charged, and aromatic side chain. Leucyl beta-naphthylamide (Leu betaNA) is the
      best substrate with the highest hydrolytic coefficiency followed by Met
      betaNA=Arg betaNA=Lys betaNA>Ala betaNA>Tyr betaNA>Phe betaNA. The cysteine-,
      metallo-, glyco-aminopeptidase releases the N-terminal Tyr from Leu-enkephalin
      with a K(m) 82microM and a k(cat) of 1.08s(-1), and Met-enkephalin with a K(m) of
      106microM and a k(cat) of 2.6s(-1). The puromycin-sensitive enzyme is most
      susceptible to amastatin with an IC(50) of 0.05microM. The data indicate that the
      enzyme is a new type of NAP found in rodent. Its possible function in neuron
      growth, neurodegeneration, and carcinomas is discussed.

PMID- 18831999
TI  - Reverse Na(+)/Ca(2+)-exchange mediated Ca(2+)-entry and noradrenaline release in
      Na(+)-loaded peripheral sympathetic nerves.
AB  - [(3)H]noradrenaline ([(3)H]NA) released from sympathetic nerves in the isolated
      main pulmonary artery of the rabbit was measured in response to field stimulation
      (2Hz, 1ms, 60V for 3min) in the presence of uptake blockers (cocaine, 3 x10(-5)M
      and corticosterone, 5 x10(-5)M). The [(3)H]NA-release was fully blocked by the
      combined application of the selective and irreversible 'N-type' voltage-sensitive
      Ca(2+)-channel (VSCC)-blocker omega-conotoxin (omega-CgTx) GVIA (10(-8)M) and the
      'non-selective' VSCC-blocker aminoglycoside antibiotic neomycin (3x10(-3)M).
      Na(+)-loading (Na(+)-pump inhibition by K(+)-free perfusion) was required to
      elicit further NA-release after blockade of VSCCs (omega-CgTx GVIA+neomycin). In
      K(+)-free solution, in the absence of functioning VSCCs (omega-CgTx
      GVIA+neomycin), the fast Na(+)-channel activator veratridine (10(-5)M) further
      potentiated the nerve-evoked release of [(3)H]NA. This NA-release was
      significantly inhibited by KB-R7943, and fully blocked by Ca(o)(2+)-removal.
      However, Li(+)-substitution was surprisingly ineffective. The non-selective K(+)
      channel blocker 4-aminopyridine (4-AP, 10(-4)M) also further potentiated the
      nerve-evoked release of NA in K(+)-free solution. This potentiated release was
      concentration-dependently inhibited by KB-R7943, significantly inhibited by Li(+)
      substitution and abolished by Ca(o)(2+)-removal. It is concluded that in Na(+)
      loaded sympathetic nerves, in which the VSCCs are blocked, the reverse
      Na(+)/Ca(2+)-exchange-mediated Ca(2+)-entry is responsible for transmitter
      release on nerve-stimulation. Theoretically we suppose that the fast Na(+)
      channel and the exchanger proteins are close to the vesicle docking sites.

PMID- 18832000
TI  - Immunohistoblot analysis on whole human hemispheres from normal and Alzheimer
      diseased brains.
AB  - We demonstrate the feasibility and usefulness of the histoblot immunostaining of
      cryosections of whole hemispheres of healthy and Alzheimer diseased (AD) human
      brains by localizing a neuron-specific marker, the anti-neuronal nuclei (NeuN)
      antigen. As expected, cortical NeuN-immunopositive regions were generally thinner
      and lighter in the AD brains than in the controls. The advantages of using whole
      hemisphere histoblots: (1) they provide a low-resolution overview/outline of the
      antigen distribution in a large surface area, (2) large, thick, and/or unfixed
      tissue sections from post-mortem samples (perhaps of inferior tissue quality) can
      be compared, and (3) subsequent immunohistochemistry can be performed on the
      tissue sections used for the histoblots.

PMID- 18832002
TI  - Advancements on phenotypic and functional characterization of non-antigen
      specific CD8+CD28- regulatory T cells.
AB  - Among the different regulatory T lymphocyte (Treg) subpopulations, non-antigen
      specific CD8+CD28- Treg (CD8+CD28- Treg) have been characterized for being
      involved in the pathogenesis of autoimmune diseases and cancer. A better
      phenotypic and functional characterization of this regulatory T-cell subset could
      help in identifying modulators of their activity with therapeutic finalities. The
      results of the present work show that Foxp3, a transcriptional marker of natural
      CD4+CD25+ Treg, is not expressed by CD8+CD28- Treg, thus indicating different
      origin and pathways of function for the latter with respect to the former
      regulatory cell type. Moreover, the results underline that the glucocorticoid
      induced TNF receptor is involved in generation processes but not in suppressor
      function of CD8+CD28- Treg. Phenotypic analyses demonstrate that, during their
      commitment from circulating nonregulatory CD8+CD28- T lymphocytes to Treg (an
      interleukin-10-dependent process), these cells downmodulate the IL7-receptor,
      thus differentiating them from long-lived, memory CD8+ T lymphocytes.
      Interestingly, CD8+CD28- Treg have been found to be resistant to the inhibitory
      effects of methylprednisolone, one of the most frequently administered
      corticosteroid drug used in therapy for immunosuppressive purposes.

PMID- 18832001
TI  - Repeated immobilization stress alters rat hippocampal and prefrontal cortical
      morphology in parallel with endogenous agmatine and arginine decarboxylase
      levels.
AB  - Agmatine, an endogenous amine derived from decarboxylation of L-arginine
      catalyzed by arginine decarboxylase, has been proposed as a neurotransmitter or
      neuromodulator in the brain. In the present study, we examined whether agmatine
      has neuroprotective effects against repeated immobilization-induced morphological
      changes in brain tissues and possible effects of immobilization stress on
      endogenous agmatine levels and arginine decarboxylase expression in rat brains.
      Sprague-Dawley rats were subjected to 2h immobilization stress daily for 7 days.
      This paradigm significantly increased plasma corticosterone levels, and the
      glutamate efflux in the hippocampus as measured by in vivo microdialysis.
      Immunohistochemical staining with beta-tubulin III showed that repeated
      immobilization caused marked morphological alterations in the hippocampus and
      medial prefrontal cortex that were prevented by simultaneous treatment with
      agmatine (50mg/kg/day), i.p.). Likewise, endogenous agmatine levels measured by
      high-performance liquid chromatography in the prefrontal cortex, hippocampus,
      striatum and hypothalamus were significantly increased by immobilization, as
      compared to controls. The increased endogenous agmatine levels, ranging from 92
      to 265% of controls, were accompanied by a significant increase of arginine
      decarboxylase protein levels in the same regions. These results demonstrate that
      the administration of exogenous agmatine protects the hippocampus and medial
      prefrontal cortex against neuronal insults caused by repeated immobilization. The
      parallel increase in endogenous brain agmatine and arginine decarboxylase protein
      levels triggered by repeated immobilization indicates that the endogenous
      agmatine system may play an important role in adaptation to stress as a potential
      neuronal self-protection mechanism.

PMID- 18832003
TI  - Naturally acquired humoral and cellular immune responses to Plasmodium vivax
      merozoite surface protein 9 in Northwestern Amazon individuals.
AB  - Antibody and T-cell reactivities to Plasmodium vivax merozoite surface protein 9
      (PvMSP9) were evaluated in a cross-sectional study of individuals naturally
      exposed to malaria infections living in Ribeirinha, a native riverine community
      and in Colina, a transmigrant community, Rondonia, Brazil. The antibody responses
      to PvMSP9-RIRIIand PvMSP9-Nt domains in Ribeirinha were higher compared with
      Colina and correlated with age and time of malaria exposure. IgG2 was most
      prevalent for PvMSP9-RII in both communities, and IgG1 was the predominant
      isotype for PvMSP9-Nt and PvMSP9-RIRII in Ribeirinha. IFN-gamma and IL-4
      predominated in Ribeirinha, while IFN-gamma predominated in Colina. Variation in
      exposure to P. vivax likely accounts for the differences observed in cytokine and
      antibody levels between the two populations studied.

PMID- 18832004
TI  - Single-dose, virus-vectored vaccine protection against Yersinia pestis challenge:
      CD4+ cells are required at the time of challenge for optimal protection.
AB  - We have developed an experimental recombinant vesicular stomatitis virus (VSV)
      vectored plague vaccine expressing a secreted form of Yersinia pestis low calcium
      response protein V (LcrV) from the first position of the VSV genome. This vector,
      given intramuscularly in a single dose, induced high-level antibody titers to
      LcrV and gave 90-100% protection against pneumonic plague challenge in mice. This
      single-dose protection was significantly better than that generated by VSV
      expressing the non-secreted LcrV protein. Increased protection correlated with
      increased anti-LcrV antibody and a bias toward IgG2a and away from IgG1 isotypes.
      We also found that the depletion of CD4+ cells, but not CD8+ cells, at the time
      of challenge resulted in reduced vaccine protection, indicating a role for
      cellular immunity in protection.

PMID- 18832005
TI  - Impaired redox state and respiratory chain enzyme activities in the cerebellum of
      vitamin A-treated rats.
AB  - Vitamin A is a micronutrient that participates in the maintenance of the
      mammalian cells homeostasis. However, excess of vitamin A, which may be achieved
      through increased intake of the vitamin either therapeutically or inadvertently,
      induces several deleterious effects in a wide range of mammalian cells, including
      neuronal cells. Vitamin A is a redox-active molecule, and it was previously
      demonstrated that it induces oxidative stress in several cell types. Therefore,
      in the present work, we investigated the effects of vitamin A supplementation at
      clinical doses (1000-9000IU/(kgday)) on redox environment and respiratory chain
      activity in the adult rat cerebellum. Glutathione-S-transferase (GST) enzyme
      activity was also measured here. The animals were treated for 3, 7, or 28 days
      with vitamin A as retinol palmitate. We found increased levels of molecular
      markers of oxidative damage in the rat cerebellum in any period analyzed.
      Additionally, vitamin A supplementation impaired cerebellar mitochondrial
      electron transfer chain (METC) activity. GST enzyme activity was increased in the
      cerebellum of rats chronically treated with vitamin A. Based on our results and
      data previously published, we recommend more caution in prescribing vitamin A at
      high doses even clinically, since there is a growing concern regarding toxic
      effects associated to vitamin A intake.

PMID- 18832006
TI  - Identification of peptides with high red blood cell and hepatocyte binding
      activity in the Plasmodium falciparum multi-stage invasion proteins: PfSPATR and
      MCP-1.
AB  - Plasmodium falciparum multi-stage proteins are involved in vital processes for
      parasite survival, which turns them into attractive targets for studies aimed at
      developing a fully effective antimalarial vaccine. MCP-1 and PfSPATR are both
      found in sporozoite and merozoite forms, and have been associated respectively
      with invasion of hepatocytes and red blood cells (RBCs). Binding assays with
      synthetic peptides derived from these two important proteins have enabled
      identifying those sequences binding with high specific activity (named High
      activity binding peptides-HABPs) to hepatoma-derived HepG2 cells and human RBCs.
      Twelve RBC HABPs were identified within the MCP-1 amino acid sequence, most of
      them in the C-terminal region. The MCP-1 HABPs 33387 and 33397 also presented
      high activity binding to HepG2 cells. PfSPATR presented four RBC HABPs and two
      HepG2 HABPs, but only one (32686) could bind to both cell types. RBC binding
      assays evidenced that binding of all HABPs was saturable and differentially
      affected by the enzymatic treatment of target cells. Moreover, all HABPs
      inhibited in vitro invasion of merozoites at 200 microM and had particular
      structural features when analyzed by circular dichroism. The results suggest that
      these synthetic peptides capable of binding to the two P. falciparum target cells
      could be potentially included in the design of a multi-stage, subunit-based,
      chemically synthesized antimalarial vaccine.

PMID- 18832007
TI  - Effects of confinement and crowding on folding of model proteins.
AB  - We perform molecular dynamics simulations for a simple coarse-grained model of
      crambin placed inside of a softly repulsive sphere of radius R. The confinement
      makes folding at the optimal temperature slower and affects the folding
      scenarios, but both effects are not dramatic. The influence of crowding on
      folding are studied by placing several identical proteins within the sphere,
      denaturing them, and then by monitoring refolding. If the interactions between
      the proteins are dominated by the excluded volume effects, the net folding times
      are essentially like for a single protein. An introduction of inter-proteinic
      attractive contacts hinders folding when the strength of the attraction exceeds
      about a half of the value of the strength of the single protein contacts. The
      bigger the strength of the attraction, the more likely is the occurrence of
      aggregation and misfolding.

PMID- 18832008
TI  - Oral administration of fructose-1,6-diphosphate has anticonvulsant activity.
AB  - Recently it has been shown that fructose-1,6-diphosphate (FDP) has dose-dependent
      anticonvulsant activity in rat models of acute generalized motor seizures induced
      with chemical convulsants. The present study asked whether FDP also has activity
      in an epileptic brain after oral administration and activity against non
      convulsive seizures. Animals (n = 14) were administered pilocarpine to induce
      status epilepticus. Several weeks later, these animals had spontaneous seizures
      and a baseline rate of seizure frequency was determined over a 6-day period.
      Animals were then continued without treatment (n = 8) or 0.5% FDP was added to
      the drinking water (n = 6). In animals treated with FDP the seizures completely
      stopped after 7 days. Removal of FDP from the water resulted in the return of
      seizure activity in 4 of the 6 animals by 16 days of observation. To induce non
      convulsive seizures, animals (n = 6) received a single injection of gamma
      butyrolactone (GBL, 100 mg/kg i.p.). All animals had spike-wave activity recorded
      in the cortex within minutes after GBL administration. Administration of a single
      injection of FDP (500 g/kg i.p.) had no effect on the baseline cortical activity,
      nor on the spike-wave activity induced by GBL (n = 5). These experiments suggest
      that oral administration of FDP may have utility in the treatment of partial or
      generalized convulsive seizure disorders, but not absence seizures.

PMID- 18832009
TI  - Localization of the Diaphanous-related formin Daam1 to neuronal dendrites.
AB  - The Rho family of small GTPase proteins are involved in the formation and
      maintenance of neuronal dendrites. In this study, we show that Daam1, a member of
      the Diaphanous-related formin protein family and a downstream effector for RhoA,
      is localized to the dendrites of hippocampal neurons. Immunoblot analysis showed
      that Daam1 is enriched in the mouse hippocampus and co-fractionates in brain
      lysates with dendritic and synaptic proteins. Immunohistochemical analysis
      revealed that Daam1 protein distributes in a punctate pattern throughout the cell
      body and dendritic shafts of dissociated hippocampal neurons and organotypic
      hippocampal cultures. Although Daam1 is mostly expressed in the shaft of
      dendrites, co-stainings with SV2 or PSD95 revealed that Daam1 is also present at
      some synapses. In addition, viral directed expression of a fluorescently tagged
      Daam1 fusion protein in hippocampal slices resulted in targeted delivery to the
      dendrites of pyramidal neurons, leading to a reduction in the density of spines.

PMID- 18832010
TI  - Effects of ageing on spinal motor and autonomic pain responses.
AB  - The course of ageing leads to various changes in the nervous system, which can
      affect pain processing in the elderly. However, the affection of different
      components of the nociceptive system remains unclear. To investigate basic
      nocifensive responses, we compared age-related changes of autonomic and motor
      reflex responses to noxious electrical stimulation. In 39 healthy young subjects
      (mean +/- S.D.; 24.1 +/- 3.3 years) and 52 healthy elderly subjects (mean +/-
      S.D.; 71.9 +/- 5.3 years) the nociceptive flexion reflex (NFR) and the
      sympathetic skin response (SSR) were determined using noxious electrical
      stimulation of the sural nerve. Verbal pain ratings were assessed in addition. No
      ageing effects on the NFR and on verbal pain ratings were found, whereas the SSR
      amplitude declined significantly with ageing. Since both SSR and NFR share
      comparable primary afferent pathways and the motor as well as the subjective
      responses to noxious stimulation were preserved, our data seem to suggest that
      central or peripheral efferent sympathetic functions are altered by age.

PMID- 18832011
TI  - Association testing of panic disorder candidate genes using CCK-4 challenge in
      healthy volunteers.
AB  - Despite continuing efforts to determine genetic vulnerability to panic disorder
      (PD), the studies of candidate genes in this disorder have produced inconsistent
      or negative, results. Laboratory panic induction may have a potential in testing
      genetic substrate of PD. In this study we aimed to explore the effects of several
      genetic polymorphisms previously implicated in PD on the susceptibility to
      cholecystokinin-tetrapeptide (CCK-4) challenge in healthy subjects. The study
      sample consisted of 110 healthy volunteers (47 males and 63 females, mean age
      22.2 +/- 5.2) who participated in CCK-4 challenge test. Nine gene-candidates,
      including 5-HTTLPR, MAO-A VNTR, TPH2 rs1386494, 5-HTR1A -1019C-G, 5-HTR2A 102T-C,
      CCKR1 246G-A, CCKR2 -215C-A, DRD1 -94G-A and COMT Val158Met, were selected for
      genotyping based on previous positive findings from genetic association studies
      in PD. After CCK-4 challenge, 39 (35.5%) subjects experienced a panic attack,
      while 71 subjects were defined as non-panickers. We detected significant
      differences for both genotypic and allelic frequencies of 1386494A/G polymorphism
      in TPH2 gene between panic and non-panic groups with the frequencies of G/G
      genotype and G allele significantly higher in panickers. None of the other
      candidate loci were significantly associated with CCK-4-induced panic attacks in
      healthy subjects. In line with our previous association study in patients with
      PD, we detected a possible association between TPH2 rs1386494 polymorphism and
      susceptibility to panic attacks. Other polymorphisms previously associated with
      PD were unrelated to CCK-4-induced panic attacks, probably due to the differences
      between complex nature of PD and laboratory panic model.

PMID- 18832012
TI  - Ca2+ oscillation induced by P2Y2 receptor activation and its regulation by a
      neuron-specific subtype of PKC (gammaPKC).
AB  - We found that stimulation of P2Y2 receptor (P2Y2R), which is endogenously
      expressed in CHO-K1 cells, induced intracellular calcium ([Ca2+]i) oscillation
      with a low frequency of 11.4 +/- 2.7 mHz. When CHO-K1 cells expressing GFP-tagged
      kinase-negative gammaPKC (gammaPKC-KN-GFP), which is a neuron-specific subtype of
      PKC, were stimulated with UDP, gammaPKC-KN-GFP, but not wild-type gammaPKC
      (gammaPKC-GFP) showed an oscillatory translocation. The oscillatory translocation
      of gammaPKC-KN-GFP corresponded with [Ca2+]i oscillation, which was not observed
      in the cells expressing gammaPKC-GFP. We examined the mechanism ofP2Y2R-induced
      [Ca2+]i oscillation pharmacologically. gammaPKC-KN-GFP oscillation was stopped by
      an extracellular Ca2+ chelator, EGTA, an antagonist of P2Y2R, Suramin, and store
      operated calcium channel (SOC) inhibitors, SKF96365 and 2-ABP. Taken together,
      P2Y2R-induced [Ca2+]i oscillation in CHO-K1 cells is related with Ca2+ influx
      through SOC, whose function may be negatively regulated by gammaPKC. This [Ca2]i
      oscillation was distinct from that induced by metabotropic glutamate receptor 5
      (mGluR5) stimulation in the frequency (72.3 +/- 5.3 mHz) and in the regulatory
      mechanism.

PMID- 18832013
TI  - Increased production of mitochondrial superoxide in the spinal cord induces pain
      behaviors in mice: the effect of mitochondrial electron transport complex
      inhibitors.
AB  - Scavengers of reactive oxygen species (ROS) have been shown to produce a strong
      antinociceptive effect on persistent pain, and mitochondria are suggested to be
      the main source of ROS in the spinal dorsal horn. To explore whether excessive
      generation of mitochondrial superoxide alone can induce pain, the effect of
      mitochondrial electron transport complex inhibitors on the development of
      mechanical hyperalgesia was examined in mice. Intrathecal injection of an
      electron transport complex inhibitor, antimycin A or rotenone, in normal mice
      resulted in a slowly developing but long-lasting and dose-dependent mechanical
      hyperalgesia. The levels of mechanical hyperalgesia after antimycin A, a complex
      III inhibitor, were higher than that with rotenone, a complex I inhibitor. A
      large increase of mitochondrial superoxide in the spinal dorsal horn and a strong
      antinociceptive effect of ROS scavengers, phenyl-N-tert-butylnitrone (PBN) and 4
      hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL) were observed in antimycin
      A-treated mice. The study indicates that the enhanced production of spinal
      mitochondrial superoxide alone without nerve injury can produce mechanical
      hyperalgesia.

PMID- 18832015
TI  - The potent non-competitive mGlu1 receptor antagonist BAY 36-7620 differentially
      affects synaptic plasticity in area cornu ammonis 1 of rat hippocampal slices and
      impairs acquisition in the water maze task in mice.
AB  - In this study we evaluated the effects of the novel, potent non-competitive
      metabotropic glutamate receptor (mGluR) 1 antagonist (3aS,6aS)-6a-naphthalen-2
      ylmethyl-5-methyliden-hexahydro-cyclopental[c]furan-1-on (BAY 36-7620) on
      different types of synaptic plasticity in the hippocampal cornu ammonis (CA) 1
      region and on hippocampus-dependent spatial learning. After having confirmed the
      presence of mGluR1 in the hippocampal CA1 region of our rat strain by confocal
      microscopy, we tested the effects of BAY 36-7620 on: 1) long-term potentiation
      (LTP) induced by weak and strong stimulation; 2) 3,5-dihydroxyphenylglycine
      (DHPG, 30 microM)-induced depression of synaptic transmission; and 3) learning of
      the hidden platform version of the water maze by mice. BAY 36-7620 (10 microM)
      amplified LTP but, like the mGluR1 antagonists 7
      hydroxyiminocyclopropan[b]chromen-1a-carboxylic acid ethyl ester (CPCCOEt, 10
      microM) and 4-carboxyphenylglycine (4-CPG, 50 microM), diminished LTP at 1
      microM. The mGluR5 antagonist 6-methyl-2-(phenylethynyl)-pyridine (MPEP, 10
      microM) had no effect. BAY 36-7620 (10 microM) did not affect strong LTP. Thus,
      mGlu 1, but not mGlu 5, receptors modulate LTP elicited by weak stimulation in
      vitro. DHPG-induced depression of synaptic transmission was only marginally
      affected by BAY 36-7620 (1 microM) or 4-CPG (100 microM). In a mouse water maze
      study, BAY 36-7620 (10 mg/kg, i.v.) increased the escape latency and impaired
      water escape task acquisition during the first 4 days. Drug- and vehicle-treated
      groups showed comparable performance at day 5. Our data support a role for mGluR1
      in LTP and in the acquisition of spatial memory.

PMID- 18832014
TI  - Time course of morphine's effects on adult hippocampal subgranular zone reveals
      preferential inhibition of cells in S phase of the cell cycle and a subpopulation
      of immature neurons.
AB  - Opiates, such as morphine, decrease neurogenesis in the adult hippocampal
      subgranular zone (SGZ), raising the possibility that decreased neurogenesis
      contributes to opiate-induced cognitive deficits. However, there is an incomplete
      understanding of how alterations in cell cycle progression and progenitor
      maturation contribute to this decrease. The present study examined how morphine
      regulates progenitor cell cycle, cell death and immature SGZ neurons (experiment
      1) as well as the progression of SGZ progenitors through key stages of maturation
      (experiment 2). In experiment 1, mice received sham or morphine pellets (s.c., 0
      and 48 h) and bromodeoxyuridine (BrdU) 2 h prior to sacrifice (24, 72 or 96 h).
      Morphine decreased both the number of S phase and total cycling cells, as there
      were fewer cells immunoreactive (IR) for the S phase marker BrdU and the cell
      cycle marker Ki67. The percentage of Ki67-IR cells that were BrdU-IR was
      decreased after 24 but not 96 h of morphine, suggesting a disproportionate effect
      on S phase cells relative to all cycling cells at this time point. Cell death
      (activated caspase-3 counts) was increased after 24 but not 96 h. In experiment
      2, nestin-green fluorescent protein (GFP) mice given BrdU 1 day prior to morphine
      or sham surgery (0 and 48 h, sacrifice 96 h) had fewer Ki67-IR cells, but no
      change in BrdU-IR cell number, suggesting that this population of BrdU-IR cells
      was less sensitive to morphine. Interestingly, examination of key stages of
      progenitor cell maturation revealed that morphine increased the percent of BrdU
      IR cells that were type 2b and decreased the percent that were immature neurons.
      These data suggest that chronic morphine decreases SGZ neurogenesis by inhibiting
      dividing cells, particularly those in S phase, and progenitor cell progression to
      a more mature neuronal stage.

PMID- 18832016
TI  - Differential expression of five members of the ADAM family in the developing
      chicken brain.
AB  - ADAMs (a disintegrin and metalloprotease) are a family of trans-membrane multi
      domain metalloproteases with multiple functions. So far, more than 35 ADAM family
      members have been identified from mammalian and nonmammalian sources. Although
      some functions of ADAMs have been elucidated, their expression patterns remain
      poorly investigated, especially during CNS development. Here, we cloned the open
      reading frames or full-length cDNAs of ADAM9, ADAM10, ADAM12, ADAM22 and ADAM23
      from chicken embryonic brain, analyzed their evolutionary relationship, and
      mapped their expression in the embryonic chicken brain by in situ hybridization
      for the first time. In general, each of the five ADAMs shows a spatially
      restricted and temporally regulated expression profile. However, the types of
      tissues and cells, which express each of the five ADAMs, differ from each other.
      ADAM9 is predominantly expressed in the choroid plexus and in the ventricular
      layer. ADAM10 is expressed by developing blood vessels, oligodendrocytes, and
      subsets of neurons and brain nuclei. ADAM12 is expressed by very few brain
      nuclei, cerebellar Purkinje cells, restricted regions of the neuroepithelium, and
      some neurons in the deep tectal layers. ADAM22 expression is strong in some brain
      nuclei and in the pineal gland. ADAM23 is expressed by most gray matter regions
      and the choroid plexus. The differential expression patterns suggest that the
      five ADAMs play multiple and versatile roles during brain development.

PMID- 18832017
TI  - Antibacterial activity of hydroxyalkenyl salicylic acids from sarcotesta of
      Ginkgo biloba against vancomycin-resistant Enterococcus.
AB  - A chloroform fraction prepared from the sarcotesta of Ginkgo biloba showed potent
      inhibitory activity against vancomycin-resistant Enterococcus (VRE). The active
      compounds were elucidated to be 2-hydroxy-6-(8-pentadecenyl) salicylic acid (1)
      and 2-hydroxy-6-(10-heptadecenyl) salicylic acid (2) based on their spectral
      analysis. Compounds 1 and 2 showed significant antibacterial activities against
      VRE.

PMID- 18832018
TI  - Mechanism of action of ZOT-derived peptide AT-1002, a tight junction regulator
      and absorption enhancer.
AB  - Tight junctions (TJs) are intercellular structures that control paracellular
      permeability and epithelial polarity. It is now accepted that TJs are highly
      dynamic structures that are regulated in response to exogenous and endogenous
      stimuli. Here, we provide details on the mechanism of action of AT-1002, the
      active domain of Vibrio cholerae's second toxin, zonula occludens toxin (ZOT). AT
      1002, a hexamer peptide, caused the redistribution of ZO-1 away from cell
      junctions as seen by fluorescence microscopy. AT-1002 also activated src and
      mitogen activated protein (MAP) kinase pathways, increased ZO-1 tyrosine
      phosphorylation, and rearrangement of actin filaments. Functionally, AT-1002
      caused a reversible reduction in transepithelial electrical resistance (TEER) and
      an increase in lucifer yellow permeability in Caco-2 cell monolayers. In vivo, co
      administration of salmon calcitonin with 1 mg of AT-1002 resulted in a 5.2-fold
      increase in AUC over the control group. Our findings provide a mechanistic
      explanation for AT-1002-induced tight junction disassembly, and demonstrate that
      AT-1002 can be used for delivery of other agents in vivo.

PMID- 18832019
TI  - Dissolution and powder flow characterization of solid self-emulsified drug
      delivery system (SEDDS).
AB  - In this study, the dynamics of powder flow upon griseofulvin-self-emulsified drug
      delivery system (SEDDS) addition to silica and silicates and the effect of these
      adsorbents on drug release were investigated. SEDDS was adsorbed at
      SEDDS/adsorbent ratios from 0.25:1 to 3:1 on magnesium aluminum silicate [5 and
      80 microm], calcium silicate [25 microm], and silicon dioxide [3.6, 20, and 300
      microm]. Powder flow was evaluated using the powder rheometer and compared to
      angle of repose. Release of drug from a 1:1 SEDDS/adsorbent powder was determined
      by dissolution using USP Type 2 apparatus. Powder rheometer profiles indicated
      that effect of SEDDS on the flow behavior of the adsorbents could be correlated
      to stepwise or continuous growing behavior as observed in wet granulation
      process. However, due to their porous nature, adsorbents exhibited an initial lag
      phase during which no change in flow was observed. Dissolution of drug from
      adsorbed-SEDDS was found to be dependent on pore length and nucleation at the
      lipid/adsorbent interface. Increase in dissolution rate was observed with an
      increase in surface area and was independent of the chemical nature of the
      adsorbents. Therefore, in order to manufacture free flowing powder containing
      liquid SEDDS, special attention should be given to particle size, specific
      surface area, type and amount of adsorbent.

PMID- 18832020
TI  - In vitro evaluation of the dissolution behaviour of itraconazole in bio-relevant
      media.
AB  - Drugs in the gastrointestinal tract are exposed to a medium of partially digested
      food, comprising mixtures of fat, protein and carbohydrate. The dissolution
      behaviour of itraconazole was evaluated in bio-relevant media which were
      developed to take this into account. Media containing milk with different fat
      contents, protein (albumin, casein, gluten and gelatin), carbohydrates (glucose,
      lactose and starch) and amino acids (lysine, glycine, alanine and aspartic acid)
      to mimic a digested meal and bile components (sodium taurocholate and lecithin)
      to represent a key endogenous digestive material were investigated. The effect of
      medium composition on the intrinsic dissolution rate of itraconazole was
      evaluated as this drug has extremely poor solubility and its bioavailability is
      affected by food. Dissolution tests were carried out in simple compendial media
      based on dilute solutions of hydrochloric acid or neutral solutions of phosphate
      buffer and in more complex media containing the dietary components. The data
      obtained showed that most of the dietary components enhanced the solubility
      compared to simulated gastric fluid (SGF) but to differing extents. The greatest
      increase in dissolution was observed with the addition of milk and albumin
      although an increase was also seen with other proteins, amino acids and simulated
      gastrointestinal fluids.

PMID- 18832021
TI  - An in vitro method for the quantitative determination of the antimicrobial
      efficacy of silver-containing wound dressings.
AB  - Treatment with silver-containing wound dressings is becoming an increasingly
      popular strategy to eliminate growth of opportunistic wound pathogens during the
      healing process. However, there are concerns over the possible side-effects of
      silver to the patient; coupled to the cost of silver as an ingredient there is a
      desire to ensure that wound dressings contain the least quantity of active
      ingredient to ensure the minimum bactericidal concentration (MBC) of silver is
      maintained in the wound environment. This requires the ability to determine the
      efficacy of silver directly within the wound environment; an extremely
      complicated task that is difficult using classical (plate counting)
      microbiological assays because these cannot be conducted in situ. Here, we report
      a quantitative method for determining the efficacy of silver in wound dressings
      using an isothermal calorimetric method. The growth curves of P. aeruginosa
      (NCIMB 8628) were recorded in growth medium and in growth medium containing
      AQUACEL Ag Hydrofiber dressing. It was found that 10 mg of dressing was
      sufficient to ensure no detectable growth of organism in 2.5 mL of medium
      inoculated to 10(6) cfu/mL. This corresponded to a silver load of 1.1x10(-6)
      moles (equivalent to 4.4x10(-4) M, in the volume of medium used in the
      experiment). Experiments conducted with silver nitrate rather than dressing
      indicated the MBC of silver against P. aeruginosa was 1x10(-4) M. The results
      suggested that not all of the silver in the dressing was bioavailable, at least
      over the lifetime of the experiment. One advantage of this effect would be the
      lack of excess availability of the silver, which allays fears of potential
      toxicity to the patient and may provide an extended period of time over which the
      dressing is bactericidal.

PMID- 18832022
TI  - Validated analysis of mortality rates demonstrates distinct genetic mechanisms
      that influence lifespan.
AB  - A key goal of gerontology is to discover the factors that influence the rate of
      senescence, which in this context refers to the age-dependent acceleration of
      mortality, inversely related to the morality rate doubling time. In contrast
      factors that influence only initial mortality rate are thought to be less
      relevant to the fundamental processes of aging. To resolve these two determinants
      of mortality rate and lifespan, initial morality rate and rate of senescence are
      calculated using the Gompertz equation. Despite theoretical and empirical
      evidence that the Gompertz parameters are most consistently and reliably
      estimated by maximum-likelihood techniques, and somewhat less so by non-linear
      regression, many researchers continue to use linear regression on the log
      transformed hazard rate. The present study compares these three methods in the
      analysis of several published studies. Estimates of the mortality rate parameters
      were then used to compare the theoretical values to the actual values of the
      following parameters: maximal lifespan, 50% survival times, variance in control
      groups and agreement with the distribution of deaths. These comparisons indicate
      that maximum-likelihood and non-linear regression estimates provide better
      estimates of mortality rate parameters than log-linear regression. Of particular
      interest, the improved estimates indicate that most genetic manipulations in mice
      that increase lifespan do so by decreasing initial mortality rate, not rate of
      senescence, whereas most genetic manipulations that decrease lifespan
      surprisingly do so by increasing the rate of senescence, not initial mortality
      rate.

PMID- 18832023
TI  - Is otospiralin inner ear specific? Evidence for its expression in mouse brain.
AB  - The small protein otospiralin has initially been identified as an inner ear
      specific molecule. However, compelling evidence from high throughput sequencing
      projects suggested that otospiralin is likely expressed in the central nervous
      system. Here, we tested this hypothesis using a combination of molecular biology,
      immunological, and histological techniques, and found that otospiralin is
      expressed in numerous regions of the central nervous system in mouse. In situ
      hybridization and immunohistochemistry revealed that otospiralin is widely
      expressed in neuronal cell bodies and glia. Ultrastructural observations in the
      cerebral cortex located the small protein in close proximity to membranous
      organelles in perikarya, the inner face of post-synaptic neuronal membranes, and
      in astrocytic processes. These results are in agreement with the predicted
      structure of the protein which revealed a single N-terminal transmembrane helix
      domain followed by a C-terminus cytosolic tail. Interestingly, 2 weeks after a
      mechanical trauma in the cerebral cortex, otospiralin expression increased in
      reactive astrocytes located within the vicinity of the site of injury, but not in
      neurons. Collectively, our observations suggest that otospiralin is possibly
      involved in signaling pathways, and could play a role in repair mechanisms
      subsequent to an injury in the central nervous system.

PMID- 18832024
TI  - Abuse pattern of toluene exposure alters mouse behavior in a waiting-for-reward
      operant task.
AB  - Inhaling solvents for recreational purposes continues to be a world-wide public
      health concern. Toluene, a volatile solvent in many abused products, adversely
      affects the central nervous system. However, the long-term neurobehavioral
      effects of exposure to high-concentration, binge patterns typical of toluene
      abuse remain understudied. We studied the behavioral effects of repeated toluene
      exposure on cognitive function following binge toluene exposure on behavioral
      impulse control in Swiss Webster mice using a "wait-for-reward" operant task.
      Mice were trained on a fixed-ratio (FR) schedule using sweetened milk as a
      reward. Upon achieving FR15, a wait component was added which delivered free
      rewards in the absence of responses at increasing time intervals (2s, 4s, 6s,
      etc...). Mice continued to receive free rewards until they pressed a lever that
      reinstated the FR component (FR Reset). Once proficient in the FR-Wait task, mice
      were exposed to either 1000 ppm, 3600 ppm or 6000 ppm toluene, or 0ppm (air
      controls) for 30 min per day for 40 days. To avoid acute effects of toluene
      exposure, behavior was assessed approximately 22-23 h later. Repeated toluene
      exposure decreased response rates, the number of FR resets, and increased mean
      wait time, resulting in a higher response-to-reinforcer ratio than exhibited by
      controls. Mice receiving the higher exposure level (6000 ppm) showed a dramatic
      decrease in the number of rewards received, which was reversed when toluene
      exposure ceased. Mice receiving the lower exposure level (1000 ppm) showed little
      change in the number of rewards. These results indicate that repeated binge
      exposures to high concentrations of toluene can significantly interfere with
      performance as measured by a waiting-for-reward task, suggesting a significant
      impact on cognitive and/or psychomotor function.

PMID- 18832025
TI  - Recycling of the human prostacyclin receptor is regulated through a direct
      interaction with Rab11a GTPase.
AB  - The human prostacyclin receptor (hIP) undergoes agonist-induced internalization
      but the mechanisms regulating its intracellular trafficking and/or recycling to
      the plasma membrane are poorly understood. Herein, we conducted a yeast-two
      hybrid screen to identify proteins interacting with the carboxyl-terminal (C)
      tail domain of the hIP and discovered a novel interaction with Rab11a. This
      interaction was confirmed by co-immunoprecipitations in mammalian HEK293 and was
      augmented by cicaprost stimulation. The hIP co-localized to Rab11-containing
      recycling endosomes in both HEK293 and endothelial EA.hy 926 cells in a time
      dependent manner following cicaprost stimulation. Moreover, over-expression of
      Rab11a significantly increased recycling of the hIP, while the dominant negative
      Rab11(S25N) impaired that recycling. Conversely, while the hIP co-localized to
      Rab4-positive endosomes in response to cicaprost, ectopic expression of Rab4a did
      not substantially affect overall recycling nor did Rab4a directly interact with
      the hIP. The specific interaction between the hIP and Rab11a was dependent on a
      22 amino acid (Val(299)-Gln(320)) sequence within its C-tail domain and was
      independent of isoprenylation of the hIP. This study elucidates a critical role
      for Rab11a in regulating trafficking of the hIP and has identified a novel Rab11
      binding domain (RBD) within its C-tail domain that is both necessary and
      sufficient to mediate interaction with Rab11a.

PMID- 18832026
TI  - Characterization of a mycothiol ligase mutant of Rhodococcus jostii RHA1.
AB  - Mycothiol (1d-myo-inosityl 2-[N-acetyl-L-cysteinyl]amido-2-deoxy-alpha-D
      glucopyranoside) is an important microbial thiol present only in actinomycetes.
      Rhodococcus jostii RHA1 degrades a wide range of xenobiotics, including
      polychlorinated biphenyls, nitriles and N-nitrosodimethylamine. Analyses revealed
      that this strain produces two thiols, mycothiol and ergothioneine, found in the
      other actinomycetes. A mycothiol ligase mutant strain of R. jostii RHA1 deficient
      in the production of mycothiol was constructed. This mutant has a number of
      interesting characteristics: (a) it overproduces the intermediate glucosamine
      inositol (1-O-(2-amino-1-deoxy-alpha-D-glucopyranosyl)-D-myo-inositol); (b) it is
      deficient in the biochemical degradation of a number of xenobiotics metabolized
      by the parent strain; (c) it shows increased susceptibility to a number of
      antibiotics; and (d) it shows unusual growth characteristics, exhibiting a long
      lag phase before normal exponential growth. The diverse phenotypes of the mutant
      indicate the utility of R. jostii RHA1 as a model for deciphering the various
      functions of mycothiol.

PMID- 18832027
TI  - Chemolithoautotrophic oxidation of thiosulfate and phylogenetic distribution of
      sulfur oxidation gene (soxB) in rhizobacteria isolated from crop plants.
AB  - Twenty-one thiosulfate-oxidizing bacteria were isolated from rhizosphere soils
      and 16S rRNA analysis revealed that the isolates were affiliated with seven
      different phylogenetic groups within the Beta and Gamma subclasses of
      Proteobacteria and Actinobacteria. Among these, five genera, including Dyella,
      Burkholderia, Alcaligenes, Microbacterium and Leifsonia sp., represented new
      sulfur oxidizers in rhizosphere soils. The thiosulfate-oxidizing Dyella,
      Burkholderia, Alcaligenes, Microbacterium, Leifsonia and Pandoraea were able to
      grow chemolithotrophically with a medium containing thiosulfate and exhibited
      growth coupled with thiosulfate oxidation. They accumulated intermediate products
      such as sulfur, sulfite and trithionate in the spent medium during the time
      course of thiosulfate oxidation, and these products were finally oxidized into
      sulfate. Furthermore, they possessed thiosulfate-metabolizing enzymes such as
      rhodanese, thiosulfate oxidase, sulfite oxidase and trithionate hydrolase,
      suggesting that these bacteria use the 'S4 intermediate' (S4I) pathway for
      thiosulfate oxidation. Phylogenetic analysis of the soxB gene revealed that
      Pandoraea sp. and Pandoraea pnomenusa strains formed a separate lineage within
      Betaproteobacteria.

PMID- 18832028
TI  - Reduction of inflammation and chronic tissue damage by omega-3 fatty acids in fat
      1 transgenic mice with pancreatitis.
AB  - Pancreatitis is a severe debilitating disease with high morbidity and mortality.
      Treatment is mostly supportive, and until now there are no clinically useful
      strategies for anti-inflammatory therapy. Although omega-3 polyunsaturated fatty
      acids (n-3 PUFA) are known to have anti-inflammatory effects, the utility of
      these fatty acids in the alleviation of pancreatitis remained to be investigated.
      The aim of this study was to examine the effect of n-3 PUFA on both acute and
      chronic pancreatitis in a well-controlled experimental system. We used the fat-1
      transgenic mouse model, characterized by endogenously increased tissue levels of
      n-3 PUFA, and their wild-type littermates to examine the effect of n-3 PUFA on
      both acute and chronic cerulein-induced pancreatitis. Disease activity and
      inflammatory status were assessed by both histology and molecular methods. In
      acute pancreatitis, fat-1 mice showed a trend towards decreased necrosis and
      significantly reduced levels of plasma IL-6 levels as well as reduced neutrophil
      infiltration in the lung. In chronic pancreatitis there was less pancreatic
      fibrosis and collagen content accompanied by decreased pancreatic stellate cell
      activation in the fat-1 animals with increased n-3 PUFA tissue levels as compared
      to wild-type littermates with high levels of omega-6 (n-6) PUFA in their tissues.
      Our data provide evidence for a reduction of systemic inflammation in acute
      pancreatitis and of tissue fibrosis in chronic pancreatitis by increasing the
      tissue content of omega-3 polyunsaturated fatty acids. These results suggest a
      beneficial potential for n-3 PUFA supplementation in acute and particularly
      chronic pancreatitis.

PMID- 18832029
TI  - Assessment of the influence factors on in vitro testing of nasal sprays using Box
      Behnken experimental design.
AB  - The purpose of the research was to investigate the influences of actuation
      parameters and formulation physical properties on nasal spray delivery
      performance using design of experiment (DOE) methodology. A 3-level, 4-factor Box
      Behnken design with a total of 27 experimental runs was used in this study. Nine
      simulated aqueous formulations with different viscosities and surface tensions
      were prepared using carboxymethylcellulose sodium (CMC, gelling agent) and
      Tween80 (surfactant) each at three concentration levels. Four factors, actuation
      stroke length, actuation velocity, concentration of gelling agent, and
      concentration of surfactant were investigated for their influences on measured
      responses of shot weight, spray pattern, plume geometry and droplet size
      distribution (DSD). The models based on data from the DOE were then optimized by
      eliminating insignificant terms. Pfeiffer nasal spray pump units filled with the
      simulated formulations were used in the study. Nasal pump actuation stroke length
      exerts a strong, independent influence on shot weight, and also slightly affects
      spray pattern and plume geometry. Actuation velocity and concentration of gelling
      agent have significant effects on spray pattern, plume geometry and DSD, in a
      complicated manner through interaction terms. Concentration of surfactant has
      little, if any, influence on nasal spray characteristics. Results were fitted to
      quadratic models describing the inherent relationships between the four factors
      evaluated and nasal spray performance. The DOE study helped us to identify the
      source of variability in nasal spray product performance, and obtained better
      understanding in how to control the variability. Moreover, the quadratic models
      developed from the DOE study quantitatively describe the inherent relationships
      between the factors and nasal spray performance characteristics. With the
      assistance of the response surfaces developed from the DOE model, the time and
      labor in designing a nasal spray product to achieve desired product performance
      characteristics can be reduced.

PMID- 18832030
TI  - Development of protein delivery microsphere system by a novel S/O/O/W multi
      emulsion.
AB  - A novel method has been developed to protect protein drugs in poly (lactic-co
      glycolic acid) (PLGA) microspheres using S/O/O/W multi-emulsion method. This
      method develops a novel protein drug sustained-release system, which is based on
      the combination of protein-loaded dextran glassy microparticles (protein-loaded
      AqueSpheres) and PLGA microspheres. The protein molecules are encapsulated in the
      dextran glassy particles and the drug-containing dextran glassy particles are
      further dispersed in the PLGA microspheres. The protein-loaded AqueSpheres based
      PLGA composite microspheres have spherical shape and a smooth surface. They
      possess a normal size distribution and a mean diameter of 67.08 microm. The
      method may decrease protein aggregations and incomplete release due to avoiding
      protein contacting with oil/water interfaces and hydrophobic PLGA. The dextran
      glassy particles can stabilize proteins in the PLGA matrix, which is the major
      advantage of this novel protein sustained-release system over preparation for the
      PLGA microspheres using W/O/W double-emulsion method.

PMID- 18832031
TI  - New concepts in chronic urticaria.
AB  - Chronic urticaria is a common skin disease without a clear etiology in the vast
      majority of cases. The similarity of symptoms and lesion pathology to allergen
      induced skin reactions supports the idea that skin mast cell and blood basophil
      IgE receptor activation is involved; however, no exogenous allergen trigger has
      been identified. The presence of serum IgG autoantibodies targeting IgE or the
      IgE receptor in approximately 40% of CIU cases supports the theory of an
      autoimmune basis for the disease. However, issues remain with the assays to
      detect autoantibodies among other serum factors, the relationship of
      autoantibodies to CIU disease activity, and the occurrence of autoantibodies in
      healthy subjects. Other studies have identified altered IgE receptor
      degranulation that reverts in disease remission and is accompanied by changes in
      signaling molecule expression and function in mast cells and basophils in active
      CIU subjects. The arrival of therapies targeting IgE and the IgE receptor pathway
      elements has potential use in CIU.

PMID- 18832032
TI  - The IL-17 cytokine family and their role in allergic inflammation.
AB  - Allergic diseases and asthma has long been hypothesized as the results of the
      dysregulation of type 2 immune responses to environmental allergens. Recent
      progresses in characterizing the proinflammatory IL-17 cytokine family have added
      additional layer of complexity on the regulation of allergic inflammation. The
      delineation of IL-17-producing CD4+ T cell subset (Th17) has led to the revision
      of Th1/Th2 paradigm and impacts our perspectives on the basis of chronic tissue
      inflammation. In addition, the distinctive expression patterns and biological
      activities of individual IL-17 cytokine member may play different roles in the
      regulation of the pathogenesis of allergic diseases. Understanding the cellular
      source and targeting cells of IL-17 cytokine family member will provide the basis
      to elucidate the cellular mechanism underlying allergic inflammation and improve
      our therapeutic approaches for allergy.

PMID- 18832033
TI  - Molecular dynamics of postsynaptic receptors and scaffold proteins.
AB  - The activity of neurotransmitter receptors determines the strength of synaptic
      transmission. Therefore, the clustering of receptors at synapses is an important
      mechanism underlying synaptic plasticity. The dynamic exchange of receptors
      between synaptic and extrasynaptic membranes is dependent on their interaction
      with synaptic scaffold proteins. Here, we review the recent advances and emerging
      concepts related to the dynamics of synaptic proteins at inhibitory and
      excitatory synapses. These include the imaging techniques that enable the study
      of protein dynamics in cells, the differences and similarities of receptor
      dynamics at excitatory and inhibitory synapses, the relationship between the
      exchange of receptor and scaffold proteins, as well as the role of receptor
      fluxes in the modulation of synaptic strength.

PMID- 18832035
TI  - Species difference exists in the effects of 1alpha,25(OH)(2)D(3) and its analogue
      2-methylene-19-nor-(20S)-1,25-dihydroxyvitamin D(3) (2MD) on osteoblastic cells.
AB  - The direct effect of 1alpha,25(OH)(2)D(3) on osteoblasts remains unclear. In this
      study, we evaluated the in vitro effects of 1alpha,25(OH)(2)D(3) and its
      analogue, 2-methylene-19-nor-(20S)-1,25-dihydroxyvitamin D(3) (2MD), on
      osteoblasts from three different species, i.e. bone marrow stromal cells from the
      Sprague-Dawley (SD) rat, from the C57BL/6 mouse, as well as human osteoblast
      NHOst cells and human osteosarcoma derived MG-63 cells. We found that in rat
      cells, both compounds increased cell proliferation, inhibited cell apoptosis and
      increased alkaline phosphatase (ALP) activity. In mouse cells, however, both
      compounds initiated cell apoptosis and inhibited ALP activity. In human cells,
      although cell proliferation was inhibited by both compounds, cell apoptosis was
      inhibited and ALP activity was enhanced. In each species, 2MD was much more
      potent than 1alpha,25(OH)(2)D(3). To summarize, species differences should be
      taken into account in studies of vitamin D effects. However, in all tested
      species - rat, mouse and human - 2MD is considerably more potent in its effects
      on osteoblastic cells in vitro than 1alpha,25(OH)(2)D(3).

PMID- 18832034
TI  - Synchronized firing in the retina.
AB  - Synchronized firing in neural populations has been proposed to constitute an
      elementary aspect of the neural code, but a complete understanding of its origins
      and significance has been elusive. Synchronized firing has been extensively
      documented in retinal ganglion cells, the output neurons of the retina. However,
      differences in synchronized firing across species and cell types have led to
      varied conclusions about its mechanisms and role in visual signaling. Recent work
      on two identified cell populations in the primate retina, the ON-parasol and OFF
      parasol cells, permits a more unified understanding. Intracellular recordings
      reveal that synchronized firing in these cell types arises primarily from common
      synaptic input to adjacent pairs of cells. Statistical analysis indicates that
      local pairwise interactions can explain the pattern of synchronized firing in the
      entire parasol cell population. Computational analysis reveals that the aggregate
      impact of synchronized firing on the visual signal is substantial. Thus, in the
      parasol cells, the origin and impact of synchronized firing on the neural code
      may be understood as locally shared input which influences the visual signals
      transmitted from eye to brain.

PMID- 18832036
TI  - Effects of selective oestrogen receptor modulators on proliferation in tissue
      cultures of pre- and postmenopausal human endometrium.
AB  - We characterised the effects of selective oestrogen receptor modulators (SERM) in
      explant cultures of human endometrium tissue. Endometrium tissues were cultured
      for 24h in Millicell-CM culture inserts in serum-free medium in the presence of
      vehicle, 17beta-estradiol (17beta-E2, 1nM), oestrogen receptor (ER) antagonist
      ICI 164.384 (40nM), and 4-OH-tamoxifen (40nM), raloxifene (4nM), lasofoxifene
      (4nM) and acolbifene (4nM). Protein expression of ERalpha, ERbeta1 and Ki-67 were
      evaluated by immunohistochemistry (IHC). The proliferative fraction was assessed
      by counting the number of Ki-67 positive cells. Nuclear staining of ER( and ER(1
      was observed in the glandular epithelium and stroma of pre- and postmenopausal
      endometrium. ER(1 protein was also localized in the endothelial cells of blood
      vessels. Treating premenopausal endometrium tissue with 17beta-E2 increased the
      fraction of Ki-67 positive cells (p<0.001) by 55% in glands compared to the
      control. Raloxifene (4nM) increased (p<0.05) the Ki-67 positive fraction. All
      other SERMS did not affect proliferation in this model. Treating postmenopausal
      endometrium with 17(-E2 increased (p<0.001) the fraction of Ki-67 positive cells
      by 250% in glands compared to the control. A similar effect was also seen for 4
      OH-tamoxifen, whereas the rest of SERMs did not stimulate proliferation. We
      demonstrated that oestradiol increases the fraction of proliferating cells in
      short term explant cultures of postmenopausal endometrium. In addition, we were
      able to reveal the agonistic properties of 4-OH-tamoxifen and confirm that
      raloxifene and next-generation SERMs acolbifene and lasofoxifene were neutral on
      the human postmenopausal endometrium.

PMID- 18832037
TI  - Reduced testicular steroidogenesis in tumor necrosis factor-alpha knockout mice.
AB  - We previously demonstrated that the expression of Mullerian inhibiting substance
      (MIS) in Sertoli cells is downregulated by tumor necrosis factor alpha (TNF
      alpha), which is secreted by meiotic germ cells, in mouse testes. Several studies
      have reported that MIS that is secreted by Sertoli cells inhibits steroidogenesis
      and, thus, the synthesis of testosterone in testicular Leydig cells. Here, we
      demonstrate that in TNF-alpha knockout testes, which show high levels of MIS,
      steroidogenesis is decreased compared to that in wild-type testes. The levels of
      testosterone and the mRNA levels of steroidogenesis-related genes were
      significantly lower after puberty in TNF-alpha knockout testes than in wild-type
      testes. Furthermore, the number of sperm was reduced in TNF-alpha knockout mice.
      Histological analysis revealed that spermatogenesis is also delayed in TNF-alpha
      knockout testes. In conclusion, TNF-alpha knockout mice show reduced testicular
      steroidogenesis, which is likely due to the high level of testicular MIS compared
      to that seen in wild-type mice.

PMID- 18832038
TI  - Dopamine receptor 3 (D3) knockout mice show regular emotional behaviour.
AB  - The "Dopamine Deficiency Hypothesis" and a considerable number of recent
      pharmacological studies propose to thoroughly verify and improve the standard of
      knowledge regarding a possible role of dopamine in the pathogenesis and treatment
      of depression. To elucidate the potential role of D3 receptors in the development
      of a depressive-like phenotype, we subjected D3 receptor knockout mice to a
      series of selected behavioural paradigms particularly focussing on depressive
      like traits. In our experimental design we exposed animals with a deficiency of
      the D3 receptor (D3-/-) to a standardised behavioural test battery, in which
      general changes of locomotion, exploration, anxiety and depressive-like
      characteristics (i.e. Learned Helplessness, Sucrose Consumption and Forced Swim
      test) can be detected. Thorough behavioural phenotyping, however, neither
      revealed behavioural consequences on the basal level (locomotion, exploration)
      nor depressive- or anxiety-like alterations. Hence, these results do not indicate
      an evident involvement of the D3 receptor in the development of a depression-like
      syndrome in mice for now. This does, however, not exclude the D3 receptor as a
      potential target for pharmacotherapy.

PMID- 18832039
TI  - Socotra Island the forgotten fragment of Gondwana: unmasking chameleon lizard
      history with complete mitochondrial genomic data.

PMID- 18832040
TI  - Depletion of the MobB and CotA complex in Aspergillus nidulans causes defects in
      polarity maintenance that can be suppressed by the environment stress.
AB  - Polarized growth is a central feature in eukaryotes. Establishment and
      maintenance of cell polarity are coordinated by signaling pathways. In this
      study, we have identified MobB is required for the regulation of cell polarity in
      Aspergillus nidulans. Depletion of MobB by alcA (p) promoter repression or
      deletion of MobB abolished conidiation completely, and induced severe growth
      defects. mobB mutants showed abnormal nuclear segregation with increased number
      of nuclei in spores, but the formation of septa occurred among dividing cells.
      The phenotype of mobB in A. nidulans is similar to that of cotA. Furthermore, we
      verified that MobB interacted with CotA to function as a complex. Interestingly,
      both mobB and cotA deletion mutants clearly exhibited filament elongation by
      using environmental osmotic stress in the media. However, calcium channel blocker
      or chelator inhibited phenotype suppression of mobB or cotA mutants. These
      results suggest that Ca2+ is potentially involved in the response to the
      suppression coupled with osmotic stabilizer. This is the first report of the
      function of MobB in A. nidulans. We propose that the MobB/CotA complex, a
      component in the conserved RAM-signaling pathway, serves an important role in
      cell morphogenesis.

PMID- 18832041
TI  - Prostaglandin E2 negatively regulates AMP-activated protein kinase via protein
      kinase A signaling pathway.
AB  - We investigated possible involvement of prostaglandin (PG) E2 in regulation of
      AMP-activated protein kinase (AMPK). When osteoblastic MG63 cells were cultured
      in serum-deprived media, Thr-172 phosphorylation of AMPK alpha-subunit was
      markedly increased. Treatment of the cells with PGE2 significantly reduced the
      phosphorylation. Ser-79 phosphorylation of acetyl-CoA carboxylase, a direct
      target for AMPK, was also reduced by PGE2. On the other hand, PGE2 reciprocally
      increased Ser-485 phosphorylation of the alpha-subunit that could be associated
      with inhibition of AMPK activity. These effects of PGE2 were mimicked by PGE2
      receptor EP2 and EP4 agonists and forskolin, but not by EP1 and EP3 agonists, and
      the effects were suppressed by an adenylate cyclase inhibitor SQ22536 and a
      protein kinase A inhibitor H89. Additionally, the PGE2 effects were duplicated in
      primary calvarial osteoblasts. Together, the present study demonstrates that PGE2
      negatively regulates AMPK activity via activation of protein kinase A signaling
      pathway.

PMID- 18832042
TI  - Improvement of microcirculation after percutaneous transluminal angioplasty in
      the lower limb with prostaglandin E1.
AB  - OBJECTIVE: The aim of the study was to investigate prospectively the
      microcirculation after angioplasty and its improvement with additional
      Prostaglandin E1 (PGE1) therapy assessed by transcutaneous pressure of oxygen.
      PATIENTS AND METHODS: 45 patients with intermittent claudication eligible for
      angioplasty were enrolled in a prospective randomised controlled clinical trial.
      Patients received either intra-arterial bolus of 40 microg PGE1 in addition to
      angioplasty or a 40 microg PGE1 intravenous infusion. Control group received no
      trial medication. Additional 15 patients undergoing intra-arterial angiography
      were also investigated. tcpO(2) values were recorded distal to the PTA region
      before, during the intervention, 24h, 2 and 4 weeks after intervention. Clinical
      endpoint was the change of tcpO(2) values 4 weeks after intervention. RESULTS:
      During the 4 week follow-up tcpO(2) values decreased in patients treated with
      angioplasty. At the same time tcpO(2) increased significantly in those patients
      additionally treated with intra-arterial PGE1 bolus injection as well as with
      intravenous PGE1 infusion. CONCLUSIONS: Impaired microcirculation after
      angioplasty can be improved with additional intravenous as well as intra-arterial
      PGE1 administration.

PMID- 18832043
TI  - Trafficking of chlamydial antigens to the endoplasmic reticulum of infected
      epithelial cells.
AB  - Confinement of the obligate intracellular bacterium Chlamydia trachomatis to a
      membrane-bound vacuole, termed an inclusion, within infected epithelial cells
      neither prevents secretion of chlamydial antigens into the host cytosol nor
      protects chlamydiae from innate immune detection. However, the details leading to
      chlamydial antigen presentation are not clear. By immunoelectron microscopy of
      infected endometrial epithelial cells and in isolated cell secretory
      compartments, chlamydial major outer membrane protein (MOMP), lipopolysaccharide
      (LPS) and the inclusion membrane protein A (IncA) were localized to the
      endoplasmic reticulum (ER) and co-localized with multiple ER markers, but not
      with markers of the endosomes, lysosomes, Golgi nor mitochondria. Chlamydial LPS
      was also co-localized with CD1d in the ER. Since the chlamydial antigens,
      contained in everted inclusion membrane vesicles, were found within the host cell
      ER, these data raise additional implications for antigen processing by infected
      uterine epithelial cells for classical and non-classical T cell antigen
      presentation.

PMID- 18832044
TI  - Soluble bacterial constituents down-regulate secretion of IL-12 in response to
      intact Gram-positive bacteria.
AB  - Intact Gram-positive bacteria induce production of large amounts of IL-12 from
      freshly isolated human monocytes. Here the bacterial structures and signalling
      pathways involved were studied and compared with those leading to IL-6
      production, and to IL-12 production in response to LPS after IFN-gamma pre
      treatment. Intact bifidobacteria induced massive production of IL-12 (1 ng/ml)
      and IL-6 (>30 ng/ml) from human PBMC, whereas fragmented bifidobacteria induced
      IL-6, but no IL-12. IL-12 production induced by intact bifidobacteria was
      inhibited by pre-treatment with bifidobacterial sonicate, peptidoglycan, muramyl
      dipeptide, lipoteichoic acid, the soluble TLR2 agonist Pam(3)Cys-SK(4), or anti
      TLR2 antibodies. Blocking of phagocytosis by cytochalasin, inhibition of the JNK
      or NF-kappaB pathways or treatment with Wortmannin also reduced the IL-12
      response to intact Gram-positive bacteria. LPS induced moderate levels of IL-12
      (0.31 ng/ml), but only from IFN-gamma pre-treated PBMC. This IL-12 production was
      enhanced by Wortmannin and unaffected by blocking the JNK pathway. Thus, intact
      Gram-positive bacteria trigger monocyte production of large amounts of IL-12 via
      a distinct pathway that is turned off by fragmented Gram-positive bacteria. This
      may be a physiological feedback, since such fragments may signal that further
      activation of the phagocyte via the IL-12/IFN-gamma loop is unnecessary.

PMID- 18832045
TI  - Repetitive transcranial magnetic stimulation in the treatment of epilepsia
      partialis continua.
AB  - OBJECTIVE: Repetitive transcranial magnetic stimulation (rTMS) is a technique for
      noninvasive focal brain stimulation by which small intracranial electrical
      currents are generated by a fluctuating extracranial magnetic field. In clinical
      epilepsy, rTMS has been applied most often interictally to reduce seizure
      frequency. Less often, rTMS has been used to terminate ongoing seizures, as in
      instances of epilepsia partialis continua (EPC). Whether ictal rTMS is effective
      and safe in the treatment of EPC has not been extensively studied. Here, we
      describe our recent experience with rTMS in the treatment of EPC, as an early
      step toward evaluating the safety and efficacy of rTMS in the treatment of
      intractable ongoing focal seizures. METHODS: Seven patients with EPC of mixed
      etiologies were treated with rTMS applied over the seizure. rTMS was delivered in
      high-frequency (20-100 Hz) bursts or as prolonged low-frequency (1 Hz) trains.
      The EEG was recorded for three of the seven patients. RESULTS: rTMS resulted in a
      brief (20-30 min) pause in seizures in three of seven patients and a lasting
      (>or=1 day) pause in two of seven. A literature search identified six additional
      reports of EPC treated with rTMS where seizures were suppressed in three of six.
      Seizures were not exacerbated by rTMS in any patient. Generally mild side effects
      included transient head and limb pain, and limb stiffening during high-frequency
      rTMS trains. CONCLUSIONS: Our clinical observations in a small number of patients
      suggest that rTMS may be safe and effective in suppressing ongoing seizures
      associated with EPC. However, a controlled trial is needed to assess the safety
      and anticonvulsive efficacy of rTMS in the treatment of EPC.

PMID- 18832046
TI  - Toxicity of dissolved Cu, Zn, Ni and Cd to developing embryos of the blue mussel
      (Mytilus trossolus) and the protective effect of dissolved organic carbon.
AB  - Marine water quality criteria for metals are largely driven by the extremely
      sensitive embryo-larval toxicity of Mytilus sp. Here we assess the toxicity of
      four dissolved metals (Cu, Zn, Ni, Cd) in the mussel Mytilus trossolus, at
      various salinity levels while also examining the modifying effects of dissolved
      organic carbon (DOC) on metal toxicity. In 48 h embryo development tests in
      natural seawater, measured EC50 values were 6.9-9.6 microg L(-1) (95% C.I.=5.5
      10.8 microg L(-1)) for Cu, 99 microg L(-1) (86-101) for Zn, 150 microg L(-1) (73
      156) for Ni, and 502 microg L(-1) (364-847) for Cd. A salinity threshold of >20
      ppt (approximately 60% full strength seawater) was required for normal control
      development. Salinity in the 60-100% range did not alter Cu toxicity.
      Experimental addition of dissolved organic carbon (DOC) from three sources
      reduced Cu toxicity; for example the EC50 of embryos developing in seawater with
      20 mg C L(-1) was 39 microg Cu L(-1) (35.2-47.2) a 4-fold increase in Cu EC50.
      The protective effects of DOC were influenced by their distinct physicochemical
      properties. Protection appears to be related to higher fulvic acid and lower
      humic acid content as operationally defined by fluorescence spectroscopy. The
      fact that DOC from freshwater sources provides protection against Cu toxicity in
      seawater suggests that extrapolation from freshwater toxicity testing may be
      possible for saltwater criteria development, including development of a saltwater
      Biotic Ligand Model for prediction of Cu toxicity.

PMID- 18832047
TI  - Molecular cloning, phylogenetic analysis and expression of a MAPEG superfamily
      gene from the pufferfish Takifugu obscurus.
AB  - The microsomal glutathione S-transferases (MGSTs) of membrane-associated proteins
      in eicosanoid and glutathione metabolism (MAPEG) superfamily play an important
      role in xenobiotics detoxification. Compared to mammals, there is limited
      information on MAPEGS from fish. We cloned a full length of cDNA sequence of a
      MGST gene from the river pufferfish (Takifugu obscurus), studied its phylogenetic
      relationship, and measured its expression in different tissues and in liver of
      fish exposed to cadmium. Phylogenetic analysis revealed that the identified gene
      encoded for MGST3. Liver showed the highest expression of MGST3 transcripts. When
      MSGT expression was compared with the expression of other GSTs (GST-Alpha, GST-Mu
      and GST-Theta), a similar pattern of highest expression was observed in the
      liver. Upon Cd exposure (5 ppm) for 96 h, the highest expression of MGST was
      observed at 24 h. GST-Mu also showed highest expression at 24 h. These findings
      indicate that MGSTs may be playing a role in detoxification of xenobiotics or
      free radicals generated by Cd-induced oxidative stress in fish.

PMID- 18832048
TI  - Morphometrics applied to medical entomology.
AB  - Morphometrics underwent a revolution more than one decade ago. In the modern
      morphometrics, the estimate of size is now contained in a single variable
      reflecting variation in many directions, as many as there are landmarks under
      study, and shape is defined as their relative positions after correcting for
      size, position and orientation. With these informative data, and the
      corresponding software freely available to conduct complex analyses, significant
      biological and epidemiological features can be quantified more accurately. We
      discuss the evolutionary significance of the environmental impact on metric
      variability, mentioning the importance of concepts like genetic assimilation,
      genetic accommodation, and epigenetics. We provide examples of measuring the
      effect of selection on metric variation by comparing (unpublished) Qst values
      with corresponding (published) Fst. The primary needs of medical entomologists
      are to distinguish species, especially cryptic species, and to detect them where
      they are not expected. We explain how geometric morphometrics could apply to
      these questions, and where there are deficiencies preventing the approach from
      being utilized at its maximum potential. Medical entomologists in connection with
      control programs aim to identify isolated populations where the risk of
      reinfestation after treatment would be low ("biogeographical islands").
      Identifying them can be obtained from estimating the number of migrants per
      generation. Direct assessment of movement remains the most valid approach, but it
      scores active movement only. Genetic methods estimating gene flow levels among
      interbreeding populations are commonly used, but gene flow does not necessarily
      mean the current flow of migrants. Methods using the morphometric variation are
      neither suited to evaluate gene flow, nor are they adapted to estimate the flow
      of migrants. They may provide, however, the information needed to create a
      preliminary map pointing to relevant areas where one could invest in using
      molecular machinery. In case of reinfesting specimens after treatment, the
      question relates to the likely source of reinfesting specimens: are they a
      residual sample not affected by the control measures, or are they individuals
      migrating from surrounding, untreated foci? We explain why the morphometric
      approach may be adapted to answer such question. Thus, we describe the
      differences between estimating the flow of migrants and identifying the source of
      reinfestation after treatment: although morphometrics is not suited to deal with
      the former, it may be an appropriate tool to address the latter.

PMID- 18832049
TI  - Dual role of CDKs in DNA repair: to be, or not to be.
AB  - The maintenance of genome integrity is essential for the regulation of cell
      proliferation and differentiation. DNA must be accurately duplicated and
      segregated to daughter cells at cell division, a process that is primarily
      regulated by cyclin-dependent kinases (CDKs). During cell growth, however, it is
      inevitable that DNA breaks will occur due to endogenous and exogenous stresses.
      Interestingly, there is increasing evidence that the catalytic activities of CDKs
      play critical roles in the DNA damage response, especially in the case of damage
      repaired by the homologous recombination (HR) pathway. In this review, we outline
      current knowledge of CDK regulation and its roles both in the unperturbed cell
      cycle and in DNA damage responses, and discuss the physiological roles of CDKs in
      HR repair.

PMID- 18832050
TI  - Enhanced gene amplification in human cells knocked down for DNA-PKcs.
AB  - Gene amplification, a key mechanism for oncogene activation and drug resistance
      in tumour cells, involves the generation and joining of DNA double-strand breaks.
      Amplified DNA can be carried either on intra-chromosomal arrays or on extra
      chromosomal elements (double minutes). We previously showed that, in rodent cells
      deficient in DNA-PKcs, intra-chromosomal amplification is significantly enhanced.
      In the present work, we studied gene amplification in human HeLa cell lines in
      which the expression of the DNA-PKcs gene was constitutively inhibited by shRNAs.
      These cell lines showed an increased sensitivity to ionizing radiations, an
      enhanced frequency of chromosomal aberrations and an increased rate of occurrence
      of methotrexate resistant colonies compared to the control cell lines (6-18
      times). The main mechanism of resistance to methotrexate was extra-chromosomal
      amplification of the dihydrofolate reductase gene. These results indicate that,
      in human cells, inhibition of DNA-PKcs gene expression favours gene amplification
      occurring via the production of double minutes. In addition, they show that cell
      lines constitutively expressing shRNAs are good model systems to study the role
      of specific functions in gene amplification.

PMID- 18832051
TI  - A high-throughput RNA interference screen for DNA repair determinants of PARP
      inhibitor sensitivity.
AB  - Synthetic lethality is an attractive strategy for the design of novel therapies
      for cancer. Using this approach we have previously demonstrated that inhibition
      of the DNA repair protein, PARP1, is synthetically lethal with deficiency of
      either of the breast cancer susceptibility proteins, BRCA1 and BRCA2. This
      observation is most likely explained by the inability of BRCA deficient cells to
      repair DNA damage by homologous recombination (HR) and has led to the clinical
      trials of potent PARP inhibitors for the treatment of BRCA mutation-associated
      cancer. To identify further determinants of PARP inhibitor response, we took a
      high-throughput genetic approach. We tested each of the genes recognised as
      having a role in DNA repair using short-interfering RNA (siRNA) and assessed the
      sensitivity of siRNA transfected cells to a potent PARP inhibitor, KU0058948. The
      validity of this approach was confirmed by the identification of known genetic
      determinants of PARP inhibitor sensitivity, including genes involved in HR. Novel
      determinants of PARP inhibitor response were also identified, including the
      transcription coupled DNA repair (TCR) proteins DDB1 and XAB2. These results
      suggest that DNA repair pathways other than HR may determine sensitivity to PARP
      inhibitors and highlight the likelihood that ostensibly distinct DNA repair
      pathways cooperate to maintain genomic stability and cellular viability.
      Furthermore, the identification of these novel determinants may eventually guide
      the optimal use of PARP inhibitors in the clinic.

PMID- 18832052
TI  - A model for the aggregation of the acylphosphatase from Sulfolobus solfataricus
      in its native-like state.
AB  - Evidence is accumulating that normally folded proteins retain a significant
      tendency to form amyloid fibrils through a direct assembly of monomers in their
      native-like conformation. However, the factors promoting such processes are not
      yet well understood. The acylphosphatase from Sulfolobus solfataricus (Sso AcP)
      aggregates under conditions in which a native-like state is initially populated
      and forms, as a first step, aggregates in which the monomers maintain their
      native-like topology. An unstructured N-terminal segment and an edge beta-strand
      were previously shown to play a major role in the process. Using kinetic
      experiments on a set of Sso AcP variants we shall show that the major event of
      the first step is the establishment of an inter-molecular interaction between the
      unstructured segment of one Sso AcP molecule and the globular unit of another
      molecule. This interaction is determined by the primary sequence of the
      unstructured segment and not by its physico-chemical properties. Moreover, we
      shall show that the conversion of these initial aggregates into amyloid-like
      protofibrils is an intra-molecular process in which the Sso AcP molecules undergo
      conformational modifications. The obtained results allow the formulation of a
      model for the assembly of Sso AcP into amyloid-like aggregates at a molecular
      level.

PMID- 18832053
TI  - Microtubule interfering agents and KSP inhibitors induce the phosphorylation of
      the nuclear protein p54(nrb), an event linked to G2/M arrest.
AB  - Microtubule interfering agents (MIAs) are anti-tumor drugs that inhibit
      microtubule dynamics, while kinesin spindle protein (KSP) inhibitors are
      substances that block the formation of the bipolar spindle during mitosis. All
      these compounds cause G2/M arrest and cell death. Using 2D-PAGE followed by Nano
      LC-ESI-Q-ToF analysis, we found that MIAs such as vincristine (Oncovin) or
      paclitaxel (Taxol) and KSP inhibitors such as S-tritil-l-cysteine induce the
      phosphorylation of the nuclear protein p54(nrb) in HeLa cells. Furthermore, we
      demonstrate that cisplatin (Platinol), an anti-tumor drug that does not cause M
      arrest, does not induce this modification. We show that the G2/M arrest induced
      by MIAs is required for p54(nrb) phosphorylation. Finally, we demonstrate that
      CDK activity is required for MIA-induced phosphorylation of p54(nrb).

PMID- 18832054
TI  - Life history of a basal bird: morphometrics of the Early Cretaceous
      Confuciusornis.
AB  - Confuciusornis sanctus stands out among the remarkable diversity of Mesozoic
      birds recently unearthed from China. Not only is this primitive beaked
      pygostylian (birds with abbreviated caudal vertebrae fused into a pygostyle) much
      more abundant than other avian taxa of this age but differences in plumage
      between specimens--some having a pair of long stiff tail feathers--have been
      interpreted as evidence for the earliest example of sexual dimorphism in birds.
      We report the results of a multivariate morphometric study involving measurements
      of more than 100 skeletons of C. sanctus. Our analyses do not show any
      correlation between size distribution and the presence or absence of blade-like
      rectrices (tail feathers), thus implying, that if these feathers are sexual
      characters, they are not correlated with sexual size dimorphism. Our results also
      provide insights into the taxonomy and life history of confuciusornithids,
      suggesting that these birds may have retained ancestral dinosaurian growth
      patterns characterized by a midlife exponential growth stage.

PMID- 18832055
TI  - Signaller: receiver coordination and the timing of communication in Amazonian
      birds.
AB  - The efficacy of communication relies on the detection of signals against
      background noise. Some species are known to alter the timing of vocalizations to
      avoid acoustic interference from similar signals of other species, but nothing is
      known about the possibility of coordinated adjustments in the timing of
      receivers' attention. I examined the possibility that co-occurring species might
      respond as well as vocalize at different times in a diverse tropical avifauna by
      presenting playbacks of recordings to territorial birds at typical and atypical
      times for singing during the dawn chorus. The results show that co-occurring
      species of birds in a diverse avifauna partition the timing of both production
      and response in a way that would reduce acoustic interference between species.

PMID- 18832056
TI  - The phylogenetic affinities of Crossley's babbler (Mystacornis crossleyi): adding
      a new niche to the vanga radiation of Madagascar.
AB  - Crossley's babbler (Mystacornis crossleyi) is a passerine endemic to Madagascar.
      Traditionally, it has been classified as a babbler (Timaliidae), although
      affinities with warblers and vangas have been suggested. We investigated the
      phylogenetic affinities of Crossley's babbler using sequence data from two
      nuclear introns (myoglobin intron 2 and beta-fibrinogen intron 5) and one
      mitochondrial gene (ND2). We present for the first time (to our knowledge) a
      molecular phylogeny that confidently places this enigmatic species within the
      vangas (Vangidae). The inclusion of Crossley's babbler within the vangas adds
      another foraging niche--gleaning small invertebrates from the ground-to this
      already large adaptive radiation of songbirds.

PMID- 18832057
TI  - Non-laminar cerebral cortex in teleost fishes?
AB  - A large skull is disadvantageous to animals that move quickly in three
      dimensional space, such as fishes and birds in water or air. A cerebral neocortex
      with a six-layered sheet has not evolved, most likely due to the limited cranial
      space. Instead of the laminar cortex, telencephalic nuclear masses seem to have
      evolved as the pallium in teleost fishes. We consider that the nuclear masses
      contain rather simple neural circuits sharing a skeleton of simple circuits in
      the mammalian cortex, which have been elaborated by additional circuits in
      mammals. Such basic similarities at the connectional level shared by nuclear and
      cortical pallium might underlie similar or equivalent functions.

PMID- 18832058
TI  - A threat to coral reefs multiplied? Four species of crown-of-thorns starfish.
AB  - In the face of ever-increasing threats to coral reef ecosystems, it is essential
      to understand the impact of natural predators in order to devise appropriate
      management strategies. Destructive population explosions of the crown-of-thorns
      starfish Acanthaster planci have devastated coral reefs throughout the Indo
      Pacific for decades. But despite extensive research, the causes of outbreaks are
      still unclear. An important consideration in this research is that A. planci has
      been regarded as a single taxonomic entity. Using molecular data from its entire
      distribution, we find that A. planci is in fact a species complex. This discovery
      has important consequences for future coral reef research, and might prove
      critical for successful reef conservation management.

PMID- 18832059
TI  - Global associations between terrestrial producer and vertebrate consumer
      diversity.
AB  - In both ecology and conservation, often a strong positive association is assumed
      between the diversity of plants as primary producers and that of animals,
      specifically primary consumers. Such a relationship has been observed at small
      spatial scales, and a begetting of diversity by diversity is expected under
      various scenarios of co-evolution and co-adaptation. But positive producer
      consumer richness relationships may also arise from similar associations with
      past opportunities for diversification or contemporary environmental conditions,
      or from emerging properties of plant diversity such as vegetation complexity or
      productivity. Here we assess whether the producer-consumer richness relationship
      generalizes from plot to regional scale and provide a first global test of its
      strength for vascular plants and endothermic vertebrates. We find strong positive
      richness associations, but only limited congruence of the most diverse regions.
      The richness of both primary and higher-level consumers increases with plant
      richness at similar strength and rate. Environmental conditions emerge as much
      stronger predictors of consumer richness, and after accounting for environmental
      differences little variation is explained by plant diversity. We conclude that
      biotic interactions and strong local associations between plants and consumers
      only relatively weakly scale up to broad geographical scales and to functionally
      diverse taxa, for which environmental constraints on richness dominate.

PMID- 18832060
TI  - Contrasted patterns of age-specific reproduction in long-lived seabirds.
AB  - While the number of studies providing evidence of actuarial senescence is
      increasing, and covers a wide range of taxa, the process of reproductive
      senescence remains poorly understood. In fact, quite high reproductive output
      until the last years of life has been reported in several vertebrate species, so
      that whether or not reproductive senescence is widespread remains unknown. We
      compared age-specific changes of reproductive parameters between two closely
      related species of long-lived seabirds: the small-sized snow petrel Pagodroma
      nivea, and the medium-sized southern fulmar Fulmarus glacialoides. Both are
      sympatric in Antarctica. We used an exceptional dataset collected over more than
      40 years to assess age-specific variations of both breeding probability and
      breeding success. We found contrasted age-specific reproductive patterns between
      the two species. Reproductive senescence clearly occurred from 21 years of age
      onwards in the southern fulmar, in both breeding probability and success, whereas
      we did not report any decline in the breeding success of the snow petrel,
      although a very late decrease in the proportion of breeders occurred at 34 years.
      Such a contrasted age-specific reproductive pattern was rather unexpected.
      Differences in life history including size or migratory behaviour are the most
      likely candidates to account for the difference we reported in reproductive
      senescence between these sympatric seabird species.

PMID- 18832061
TI  - Experimental evolution of a microbial predator's ability to find prey.
AB  - Foraging theory seeks to explain how the distribution and abundance of prey
      influence the evolution of predatory behaviour, including the allocation of
      effort to searching for prey and handling them after they are found. While
      experiments have shown that many predators alter their behaviour phenotypically
      within individual lifetimes, few have examined the actual evolution of predatory
      behaviour in light of this theory. Here, we test the effects of prey density on
      the evolution of a predator's searching and handling behaviours using a bacterial
      predator, Myxococcus xanthus. Sixteen predator populations evolved for almost a
      year on agar surfaces containing patches of Escherichia coli prey at low or high
      density. Improvements in searching rate were significantly greater in those
      predators that evolved at low prey density. Handling performance also improved in
      some predator populations, but prey density did not significantly affect the
      magnitude of these gains. As the predators evolved greater foraging proficiency,
      their capacity diminished to produce fruiting bodies that enable them to survive
      prolonged periods of starvation. More generally, these results demonstrate that
      predators evolve behaviours that reflect at least some of the opportunities and
      limitations imposed by the distribution and abundance of their prey.

PMID- 18832062
TI  - The jury is in: p73 is a tumor suppressor after all.
AB  - While p53 has been extensively characterized as a tumor suppressor, it has been
      more difficult to determine whether p63 and/or p73 play a similar role. Every
      system in which these family members have been studied, from cells to animal
      models to human tissues, seems to create more questions than answers. Tomasini
      and colleagues (2677-2691) demonstrate that one isoform of p73 is responsible for
      preventing tumor formation in vivo, providing critical validation of an isoform
      based model of p73 function.

PMID- 18832063
TI  - Deconstructing meiosis one kinase at a time: polo pushes past pachytene.
AB  - The transition from pachytene to Meiosis I is a key regulatory point in yeast
      meiosis. This transition requires Ndt80, a transcription factor that commits
      cells to complete meiosis by expression of a diverse set of genes. In this issue
      of Genes & Development, Sourirajan and Lichten (2627-2632) report that CDC5, an
      NDT80-regulated gene encoding yeast polo-like kinase, is sufficient for Holliday
      junction resolution and exit from pachytene. Determining the meiotic targets of
      Cdc5 therefore provides a new approach for identifying a eukaryotic Holliday
      resolvase.

PMID- 18832064
TI  - Signal integration in bacterial two-component regulatory systems.
AB  - Two-component systems (TCSs) and phosphorelays are key mediators of bacterial
      signal transduction. The signals activating these systems promote the
      phosphorylated state of a response regulator, which is generally the form that
      carries out specific functions such as binding to DNA and catalysis of
      biochemical reactions. An emerging class of proteins-termed TCS connectors
      modulate the output of TCSs by affecting the phosphorylation state of response
      regulators. TCS connectors use different mechanisms of action for signal
      integration, as well as in the coordination and fine-tuning of cellular
      processes. Present in both Gram-positive and Gram-negative bacteria, TCS
      connectors are critical for a variety of physiological functions including
      sporulation, competence, antibiotic resistance, and the transition to stationary
      phase.

PMID- 18832065
TI  - Meeting DNA palindromes head-to-head.
AB  - Particular DNA sequences have long been known to have exceptional structures and
      biological properties. Famous in the medical world are the trinucleotide repeat
      sequences, such as (CTG)(n), and their association with more than a dozen
      neurodegenerative diseases. Numerous meetings have been held to discuss these
      repeats and the diseases they cause. Now, a much-needed meeting has been held to
      discuss other noncanonical (non-B-form) DNA structures, their properties, and
      their biological consequences. Although the meeting was titled "DNA palindromes:
      roles, consequences, and implications of structurally ambivalent DNA," the
      participants discussed and debated a range of additional structures-dubbed "Z,"
      "HJ," "G4," and "H" DNA-as well as trinucleotide repeats. These remarkable
      structures can have profound effects on chromosomes and organisms, ranging from
      mutational hotspots in bacteria to causes of intellectual disability in humans.
      Bringing together four dozen researchers prominent in the field focused attention
      on these controversial DNA structures in a way that promises to spur greater
      understanding of DNA elements critical to life and health.

PMID- 18832066
TI  - Polo-like kinase Cdc5 drives exit from pachytene during budding yeast meiosis.
AB  - In budding yeast, exit from the pachytene stage of meiosis requires the mid
      meiosis transcription factor Ndt80, which promotes expression of approximately
      200 genes. Ndt80 is required for meiotic function of polo-like kinase (PLK, Cdc5)
      and cyclin-dependent kinase (CDK), two cell cycle kinases previously implicated
      in pachytene exit. We show that ongoing CDK activity is dispensable for two
      events that accompany exit from pachytene: crossover formation and synaptonemal
      complex breakdown. In contrast, CDC5 expression in ndt80Delta mutants efficiently
      promotes both events. Thus, Cdc5 is the only member of the Ndt80 transcriptome
      required for this critical step in meiotic progression.

PMID- 18832067
TI  - HBO1 histone acetylase is a coactivator of the replication licensing factor Cdt1.
AB  - HBO1 histone acetylase is important for DNA replication licensing. In human
      cells, HBO1 associates with replication origins specifically during the G1 phase
      of the cell cycle in a manner that depends on the replication licensing factor
      Cdt1, but is independent of the Cdt1 repressor Geminin. HBO1 directly interacts
      with Cdt1, and it enhances Cdt1-dependent rereplication. Thus, HBO1 plays a
      direct role at replication origins as a coactivator of the Cdt1 licensing factor.
      As HBO1 is also a transcriptional coactivator, it has the potential to integrate
      internal and external stimuli to coordinate transcriptional responses with
      initiation of DNA replication.

PMID- 18832068
TI  - Histone deacetylase 3 is required for centromeric H3K4 deacetylation and sister
      chromatid cohesion.
AB  - We describe here the role of histone deacetylase 3 (HDAC3) in sister chromatid
      cohesion and the deacetylation of histone H3 Lys 4 (H3K4) at the centromere.
      HDAC3 knockdown induced spindle assembly checkpoint activation and sister
      chromatid dissociation. The depletion of Polo-like kinase 1 (Plk1) or Aurora B
      restored cohesion in HDAC3-depleted cells. HDAC3 was also required for Shugoshin
      localization at centromeres. Finally, we show that HDAC3 depletion results in the
      acetylation of centromeric H3K4, correlated with a loss of dimethylation at the
      same position. These findings provide a functional link between sister chromatid
      cohesion and the mitotic "histone code".

PMID- 18832069
TI  - Proteoglycan desulfation determines the efficiency of chondrocyte autophagy and
      the extent of FGF signaling during endochondral ossification.
AB  - Cartilage extracellular matrix (ECM) contains large amounts of proteoglycans made
      of a protein core decorated by highly sulfated sugar chains, the
      glycosaminoglycans (GAGs). GAGs desulfation, a necessary step for their
      degradation, is exerted by sulfatases that are activated by another enzyme,
      Sulfatase-Modifying Factor 1 (SUMF1), whose inactivation in humans leads to
      severe skeletal abnormalities. We show here that despite being expressed in both
      osteoblasts and chondrocytes Sumf1 does not affect osteoblast differentiation.
      Conversely, in chondrocytes it favors ECM production and autophagy and promotes
      proliferation and differentiation by limiting FGF signaling. Thus, proteoglycan
      desulfation is a critical regulator of chondrogenesis.

PMID- 18832070
TI  - A genome-scale analysis of the cis-regulatory circuitry underlying sonic hedgehog
      mediated patterning of the mammalian limb.
AB  - Sonic hedgehog (Shh) signals via Gli transcription factors to direct digit number
      and identity in the vertebrate limb. We characterized the Gli-dependent cis
      regulatory network through a combination of whole-genome chromatin
      immunoprecipitation (ChIP)-on-chip and transcriptional profiling of the
      developing mouse limb. These analyses identified approximately 5000 high-quality
      Gli3-binding sites, including all known Gli-dependent enhancers. Discrete binding
      regions exhibit a higher-order clustering, highlighting the complexity of cis
      regulatory interactions. Further, Gli3 binds inertly to previously identified
      neural-specific Gli enhancers, demonstrating the accessibility of their cis
      regulatory elements. Intersection of DNA binding data with gene expression
      profiles predicted 205 putative limb target genes. A subset of putative cis
      regulatory regions were analyzed in transgenic embryos, establishing Blimp1 as a
      direct Gli target and identifying Gli activator signaling in a direct, long-range
      regulation of the BMP antagonist Gremlin. In contrast, a long-range silencer
      cassette downstream from Hand2 likely mediates Gli3 repression in the anterior
      limb. These studies provide the first comprehensive characterization of the
      transcriptional output of a Shh-patterning process in the mammalian embryo and a
      framework for elaborating regulatory networks in the developing limb.

PMID- 18832071
TI  - The histone H2B-specific ubiquitin ligase RNF20/hBRE1 acts as a putative tumor
      suppressor through selective regulation of gene expression.
AB  - Histone monoubiquitylation is implicated in critical regulatory processes. We
      explored the roles of histone H2B ubiquitylation in human cells by reducing the
      expression of hBRE1/RNF20, the major H2B-specific E3 ubiquitin ligase. While H2B
      ubiquitylation is broadly associated with transcribed genes, only a subset of
      genes was transcriptionally affected by RNF20 depletion and abrogation of H2B
      ubiquitylation. Gene expression dependent on RNF20 includes histones H2A and H2B
      and the p53 tumor suppressor. In contrast, RNF20 suppresses the expression of
      several proto-oncogenes, which reside preferentially in closed chromatin and are
      modestly transcribed despite bearing marks usually associated with high
      transcription rates. Remarkably, RNF20 depletion augmented the transcriptional
      effects of epidermal growth factor (EGF), increased cell migration, and elicited
      transformation and tumorigenesis. Furthermore, frequent RNF20 promoter
      hypermethylation was observed in tumors. RNF20 may thus be a putative tumor
      suppressor, acting through selective regulation of a distinct subset of genes.

PMID- 18832072
TI  - Role of Cdx2 and cell polarity in cell allocation and specification of
      trophectoderm and inner cell mass in the mouse embryo.
AB  - Genesis of the trophectoderm and inner cell mass (ICM) lineages occurs in two
      stages. It is initiated via asymmetric divisions of eight- and 16-cell
      blastomeres that allocate cells to inner and outer positions, each with different
      developmental fates. Outside cells become committed to the trophectoderm at the
      blastocyst stage through Cdx2 activity, but here we show that Cdx2 can also act
      earlier to influence cell allocation. Increasing Cdx2 levels in individual
      blastomeres promotes symmetric divisions, thereby allocating more cells to the
      trophectoderm, whereas reducing Cdx2 promotes asymmetric divisions and
      consequently contribution to the ICM. Furthermore, both Cdx2 mRNA and protein
      levels are heterogeneous at the eight-cell stage. This heterogeneity depends on
      cell origin and has developmental consequences. Cdx2 expression is minimal in
      cells with unrestricted developmental potential that contribute preferentially to
      the ICM and is maximal in cells with reduced potential that contribute more to
      the trophectoderm. Finally, we describe a mutually reinforcing relationship
      between cellular polarity and Cdx2: Cdx2 influences cell polarity by up
      regulating aPKC, but cell polarity also influences Cdx2 through asymmetric
      distribution of Cdx2 mRNA in polarized blastomeres. Thus, divisions generating
      inside and outside cells are truly asymmetric with respect to cell fate
      instructions. These two interacting effects ensure the generation of a stable
      outer epithelium by the blastocyst stage.

PMID- 18832073
TI  - Sequestration of Polo kinase to microtubules by phosphopriming-independent
      binding to Map205 is relieved by phosphorylation at a CDK site in mitosis.
AB  - The conserved Polo kinase controls multiple events in mitosis and cytokinesis.
      Although Polo-like kinases are regulated by phosphorylation and proteolysis,
      control of subcellular localization plays a major role in coordinating their
      mitotic functions. This is achieved largely by the Polo-Box Domain, which binds
      prephosphorylated targets. However, it remains unclear whether and how Polo might
      interact with partner proteins when priming mitotic kinases are inactive. Here we
      show that Polo associates with microtubules in interphase and cytokinesis,
      through a strong interaction with the microtubule-associated protein Map205.
      Surprisingly, this interaction does not require priming phosphorylation of
      Map205, and the Polo-Box Domain of Polo is required but not sufficient for this
      interaction. Moreover, phosphorylation of Map205 at a CDK site relieves this
      interaction. Map205 can stabilize Polo and inhibit its cellular activity in vivo.
      In syncytial embryos, the centrosome defects observed in polo hypomorphs are
      enhanced by overexpression of Map205 and suppressed by its deletion. We propose
      that Map205-dependent targeting of Polo to microtubules provides a stable
      reservoir of Polo that can be rapidly mobilized by the activity of Cdk1 at
      mitotic entry.

PMID- 18832074
TI  - SHC-1/p52Shc targets the insulin/IGF-1 and JNK signaling pathways to modulate
      life span and stress response in C. elegans.
AB  - Correlative evidence links stress, accumulation of oxidative cellular damage, and
      aging in several species. Genetic studies in species ranging from yeast to
      mammals revealed several pathways regulating stress response and life span,
      including caloric intake, mitochondrial respiration, insulin/IGF-1 (IIS), and JNK
      (c-Jun N-terminal kinase) signaling. How IIS and JNK signaling cross-talk to
      defend against diverse stressors contributing to aging is of critical importance
      but, so far, only poorly understood. In this study, we demonstrate that the
      adaptor protein SHC-1, the Caenorhabditis elegans homolog of human p52Shc,
      coordinates mechanisms of stress response and aging. Using genetic and
      biochemical approaches, we discover that SHC-1 not only opposes IIS but also
      activates JNK signaling. Loss of shc-1 function results in accelerated aging and
      enhanced sensitivity to heat, oxidative stress, and heavy metals, whereas
      expression of human p52Shc rescues the shc-1 mutant phenotype. SHC-1 acts
      upstream of the insulin/IGF receptor DAF-2 and the PI3 kinase AGE-1 and directly
      interacts with DAF-2. Moreover, SHC-1 activates JNK signaling by binding to MEK-1
      kinase. Both aspects converge on controlling the nuclear translocation and
      activation of the FOXO transcription factor DAF-16. Our findings establish C.
      elegans SHC-1 as a critical scaffold that directly cross-connects the two
      parallel JNK and IIS pathways and help to explain how these signaling cascades
      cooperate to ascertain normal stress response and life span in C. elegans.

PMID- 18832075
TI  - Eye gaze during comprehension of American Sign Language by native and beginning
      signers.
AB  - An eye-tracking experiment investigated where deaf native signers (N = 9) and
      hearing beginning signers (N = 10) look while comprehending a short narrative and
      a spatial description in American Sign Language produced live by a fluent signer.
      Both groups fixated primarily on the signer's face (more than 80% of the time)
      but differed with respect to fixation location. Beginning signers fixated on or
      near the signer's mouth, perhaps to better perceive English mouthing, whereas
      native signers tended to fixate on or near the eyes. Beginning signers shifted
      gaze away from the signer's face more frequently than native signers, but the
      pattern of gaze shifts was similar for both groups. When a shift in gaze
      occurred, the sign narrator was almost always looking at his or her hands and was
      most often producing a classifier construction. We conclude that joint visual
      attention and attention to mouthing (for beginning signers), rather than
      linguistic complexity or processing load, affect gaze fixation patterns during
      sign language comprehension.

PMID- 18832076
TI  - Signalling loops and linear pathways: NF-kappaB activation in response to
      genotoxic stress.
AB  - The signalling loop concept was introduced in 1991 to explain activation of
      membrane and cytoplasmic kinases in response to DNA damage inflicted by ionizing
      radiation. Damage to the chromosomal DNA was thought to provide a primary signal
      and a secondary signal from a nucleus to cytoplasm was assumed. This scenario was
      confirmed although not as originally proposed. A complex of nuclear factor-kappaB
      (NF-kappaB) essential modulator and ataxia telangiectasia-mutated kinase
      activated by genotoxic agents is sent to cytoplasm, prompting nuclear
      translocation of the active transcription factor NF-kappaB. In parallel, linear
      signalling pathways are initiated in the cytoplasm, mostly by reactive oxygen
      species, resulting in NF-kappaB activation and nuclear translocation. The choice
      of NF-kappaB activation pathway and the extent of activation of various pathways
      may be influenced by the relative degree of damage inflicted by genotoxic agents
      in the nuclear and cytoplasmic compartments. The ultimate pattern of cellular
      response is determined by availability, abundance and localization of the
      proteins participating in the signal transduction.

PMID- 18832077
TI  - Different selective pressures shape the molecular evolution of color vision in
      chimpanzee and human populations.
AB  - A population genetic analysis of the long-wavelength opsin (OPN1LW, "red") color
      vision gene in a global sample of 236 human nucleotide sequences had previously
      discovered nine amino acid replacement single nucleotide polymorphisms, which
      were found at high frequencies in both African and non-African populations and
      associated with an unusual haplotype diversity. Although this pattern of
      nucleotide diversity is consistent with balancing selection, it has been argued
      that a recombination "hot spot" or gene conversion within and between X-linked
      color vision genes alone may explain these patterns. The current analysis
      investigates a closely related primate with trichromatism to determine whether
      color vision gene amino acid polymorphism and signatures of adaptive evolution
      are characteristic of humans alone. Our population sample of 56 chimpanzee (Pan
      troglodytes) OPN1LW sequences shows three singleton amino acid polymorphisms and
      no unusual recombination or linkage disequilibrium patterns across the
      approximately 5.5-kb region analyzed. Our comparative population genetic approach
      shows that the patterns of OPN1LW variation in humans and chimpanzees are
      consistent with positive and purifying selection within the two lineages,
      respectively. Although the complex role of color vision has been greatly
      documented in primate evolution in general, it is surprising that trichromatism
      has followed very different selective trajectories even between humans and our
      closest relatives.

PMID- 18832078
TI  - The genetic basis of phenotypic convergence in beach mice: similar pigment
      patterns but different genes.
AB  - Convergent evolution is a widespread phenomenon seen in diverse organisms
      inhabiting similar selective environments. However, it is unclear if similar
      phenotypes are produced by the same or different genes and mutations. Here we
      analyze the molecular mechanisms underlying convergent pigment pattern among
      subspecies of the beach mouse (Peromyscus polionotus) inhabiting the Gulf and
      Atlantic coasts of Florida. In these two geographic regions, separated by more
      than 300 km, "beach mice" have lighter colored coats than do their mainland
      counterparts, produced by natural selection for camouflage against the pale
      coastal sand dunes. We measured color pattern in eight beach mouse subspecies and
      showed that three of the Gulf Coast subspecies are more phenotypically similar to
      an Atlantic coast subspecies than to their Gulf Coast neighbors. However, light
      colored beach mice do not form a monophyletic group. Previous results implicated
      a single derived amino acid change in the melanocortin-1 receptor (Mc1r) as a
      major contributor to pigment pattern in the Gulf Coast beach mice; despite
      phenotypic similarities, the derived Mc1r allele was not found in the Atlantic
      coast beach mouse populations. Here we show that Atlantic coast beach mice have
      high levels of Mc1r polymorphism but they lack unique alleles. Functional assays
      revealed that single amino acid mutations segregating in Atlantic coast beach
      mice do not cause any change in Mc1r activity compared with the activity of Mc1r
      from dark-colored mice. These joint results show that convergent pigment patterns
      in recently diverged beach mouse subspecies--whose developmental constraints are
      presumably similar--have evolved through a diversity of genetic mechanisms.

PMID- 18832079
TI  - Comprehensive analysis of archaeal tRNA genes reveals rapid increase of tRNA
      introns in the order thermoproteales.
AB  - The analysis of archaeal tRNA genes is becoming more important to evaluate the
      origin and evolution of tRNA molecule. Even with the recent accumulation of
      complete genomes of numerous archaeal species, several tRNA genes are still
      required for a full complement of the codon table. We conducted comprehensive
      screening of tRNA genes from 47 archaeal genomes by using a combination of
      different types of tRNA prediction programs and extracted a total of 2,143
      reliable tRNA gene candidates including 437 intron-containing tRNA genes, which
      covered more than 99.9% of the codon tables in Archaea. Previously, the content
      of intron-containing tRNA genes in Archaea was estimated to be approximately 15%
      of the whole tRNA genes, and most of the introns were known to be located at
      canonical positions (nucleotide position between 37 and 38) of precursor tRNA
      (pre-tRNA). Surprisingly, we observed marked enrichment of tRNA introns in five
      species of the archaeal order Thermoproteales; about 70% of tRNA gene candidates
      were found to be intron-containing tRNA genes, half of which contained multiple
      introns, and the introns were located at various noncanonical positions. Sequence
      similarity analysis revealed that approximately half of the tRNA introns found at
      Thermoproteales-specific intron locations were highly conserved among several
      tRNA genes. Intriguingly, identical tRNA intron sequences were found within
      different types of tRNA genes that completely lacked exon sequence similarity,
      suggesting that the tRNA introns in Thermoproteales could have been gained via
      intron insertion events at a later stage of tRNA evolution. Moreover, although
      the CCA sequence at the 3' terminal of pre-tRNA is added by a CCA-adding enzyme
      after gene transcription in Archaea, most of the tRNA genes containing highly
      conserved introns already encode the CCA sequence at their 3' terminal. Based on
      these results, we propose possible models explaining the rapid increase of tRNA
      introns as a result of intron insertion events via retrotransposition of pre
      tRNAs. The sequences and secondary structures of the tRNA genes and their bulge
      helix-bulge motifs were registered in SPLITSdb
      (http://splits.iab.keio.ac.jp/splitsdb/), a novel and comprehensive database for
      archaeal tRNA genes.

PMID- 18832080
TI  - Placental HIFs as markers of cerebral hypoxic distress in fetal mice.
AB  - Reduced oxygen supply during the pre- and perinatal period often leads to
      acquired neonatal brain damage. So far, there are no reliable markers available
      to assess the hypoxic cerebral damage and the resulting prognosis during the
      immediate postnatal period. Thus we aimed to determine whether the hypoxia
      inducible transcription factors (HIF-1 and HIF-2) and/or their target genes in
      the placenta represent reliable indicators of hypoxic distress of the developing
      brain during systemic hypoxia at the end of gestation. To this end, pregnant mice
      were exposed to systemic hypoxia (inspired O2 fraction: 6%, 6 h) at gestational
      day 20. This hypoxic exposure significantly increased HIF-1alpha and HIF-2alpha
      protein levels in brain and placental tissue. Compared with normoxic controls, an
      increase of HIF-1alpha-immunoreactive neurons and HIF-2alpha-positive glial cells
      and vascular endothelial cells was observed in hypoxic cerebral cortex and
      hippocampus. In placenta, HIF-1alpha and HIF-2alpha were expressed in
      labyrinthine layer with increased staining intensity during hypoxia compared with
      normoxia. Significant upregulation of VEGF mRNA and protein in brain and
      placenta, as well as erythropoietin protein in placenta, indicated activity of
      the HIF system upon fetal hypoxia. Notably, hypoxia did not affect expression of
      the HIF target genes inducible nitric oxide synthase and GLUT-1. Taken together,
      at gestational day 20, systemic hypoxia led to upregulation of HIF-alpha in mouse
      brain that was temporally paralleled in placenta, implying that alpha-subunits of
      both HIF-1 and HIF-2 are indeed early markers of hypoxic distress in vivo. If our
      data reflect the situation in humans, analysis of the placenta will allow early
      identification of the hypoxic brain distress occurring near birth.

PMID- 18832081
TI  - The role of inhibitory heterotrimeric G proteins in the control of in vivo heart
      rate dynamics.
AB  - Multiple isoforms of inhibitory Galpha-subunits (Galphai1,2,3, as well as
      Galphao) are present within the heart, and their role in modulating pacemaker
      function remains unresolved. Do inhibitory Galpha-subunits selectively modulate
      parasympathetic heart rate responses? Published findings using a variety of
      experimental approaches have implicated roles for Galphai2, Galphai3, and Galphao
      in parasympathetic signal transduction. We have compared in vivo different groups
      of mice with global genetic deletion of Gialpha1/Galphai3, Galphai2, and Galphao
      against littermate controls using implanted ECG telemetry. Significant resting
      tachycardia was observed in Galphai2(-/-) and Galphao(-/-) mice compared with
      control and Galphai1(-/-)/Galphai3(-/-) mice (P < 0.05). Loss of diurnal heart
      rate variation was seen exclusively in Galphao(-/-) mice. Using heart rate
      variability (HRV) analysis, compared with littermate controls (4.02 ms2 +/- 1.17;
      n = 6, Galphai2(-/-)) mice have a selective attenuation of high-frequency (HF)
      power (0.73 ms2 +/- 0.31; n = 5, P < 0.05). Galphai1(-/-)/Galphai3(-/-) and
      Galphao(-/-) cohorts have nonsignificant changes in HF power. Galphao(-/-) mice
      have a different basal HRV signature. The observed HRV phenotype in Galphai2(-/-)
      mice was qualitatively similar to atropine (1 mg/kg)-treated controls [and mice
      treated with the GIRK channel blocker tertiapinQ (0.05 mg/kg)]. Maximal
      cardioinhibitory response to the M(2)-receptor agonist carbachol (0.5 mg/kg)
      compared with basal heart rate was attenuated in Galphai2(-/-) mice (0.08 +/-
      0.04; n = 6) compared to control (0.27 +/- 0.04; n = 7 P < 0.05). Our data
      suggest a selective defect of parasympathetic heart rate modulation in mice with
      Galphai2 deletion. Mice with Galphao deletion also have a defect in short-term
      heart rate dynamics, but this is qualitatively different to the effects of
      atropine, tertiapinQ, and Galphai2 deletion. In contrast, Galphai1 and Galphai3
      do not appear to be essential for parasympathetic responses in vivo.

PMID- 18832082
TI  - Microarray analysis of the transcriptome of the subfornical organ in the rat:
      regulation by fluid and food deprivation.
AB  - We have employed microarray technology using Affymetrix 230 2.0 genome chips to
      initially catalog the transcriptome of the subfornical organ (SFO) under control
      conditions and to also evaluate the changes (common and differential) in gene
      expression induced by the challenges of fluid and food deprivation. We have
      identified a total of 17,293 genes tagged as present in one of our three
      experimental conditions, transcripts, which were then used as the basis for
      further filtering and statistical analysis. In total, the expression of 46 genes
      was changed in the SFO following dehydration compared with control animals (22
      upregulated and 24 downregulated), with the largest change being the greater than
      fivefold increase in brain-derived neurotrophic factor (BDNF) expression, while
      significant changes in the expression of the calcium-sensing (upregulated) and
      apelin (downregulated) receptors were also reported. In contrast, food
      deprivation caused greater than twofold changes in a total of 687 transcripts
      (222 upregulated and 465 downregulated), including significant reductions in
      vasopressin, oxytocin, promelanin concentrating hormone, cocaine amphetamine
      related transcript (CART), and the endothelin type B receptor, as well as
      increases in the expression of the GABA(B) receptor. Of these regulated
      transcripts, we identified 37 that are commonly regulated by fasting and
      dehydration, nine that were uniquely regulated by dehydration, and 650 that are
      uniquely regulated by fasting. We also found five transcripts that were
      differentially regulated by fasting and dehydration including BDNF and CART. In
      these studies we have for the first time described the transcriptome of the rat
      SFO and have in addition identified genes, the expression of which is
      significantly modified by either water or food deprivation.

PMID- 18832083
TI  - Modular control analysis of effects of chronic hypoxia on mouse heart.
AB  - Modular control analysis (MoCA; Diolez P, Deschodt-Arsac V, Raffard G, Simon C,
      Santos PD, Thiaudiere E, Arsac L, Franconi JM. Am J Physiol Regul Integr Comp
      Physiol 293: R13-R19, 2007) was applied here on perfused hearts to describe the
      modifications of the regulation of heart energetics induced in mice exposed to 3
      wk chronic hypoxia. MoCA combines 31P-NMR spectroscopy and modular (top down)
      control analysis to describe the integrative regulation of energy metabolism in
      the intact beating heart, on the basis of two modules [ATP/phosphocreatine (PCr)
      production and ATP/PCr consumption] connected by the energetic intermediates. In
      contrast with previous results in rat heart, in which all control of contraction
      was on ATP demand, mouse heart energetics presented a shared control of
      contraction between ATP/PCr-producing and -consuming modules. In chronic hypoxic
      mice, the decrease in heart contractile activity and PCr-to-ATP ratio was
      surprisingly associated with an important and significant higher response of
      ATP/PCr production (elasticity) to PCr changes compared with control hearts (
      10.4 vs. -2.46). By contrast, no changes were observed in ATP/PCr consumption
      since comparable elasticities were observed. Since elasticities determine the
      regulation of energetics of heart contraction, the present results show that this
      new parameter may be used to uncover the origin of the observed dysfunctions
      under chronic hypoxia conditions. Considering the decrease in mitochondrial
      content reported after exposure to chronic hypoxia, it appears that the
      improvement of ATP/PCr production response to ATP demand may be viewed as a
      positive adaptative mechanism. It now appears crucial to understand the very
      processes responsible for ATP/PCr producer elasticity toward the energetic
      intermediates, as well as their regulation.

PMID- 18832084
TI  - Chronic myocardial infarction induces phenotypic and functional remodeling in the
      guinea pig cardiac plexus.
AB  - Chronic myocardial infarction (CMI) is associated with remodeling of the
      ventricle and evokes adaption in the cardiac neurohumoral control systems. To
      evaluate the remodeling of the intrinsic cardiac nervous system following
      myocardial infarction, the dorsal descending coronary artery was ligated in the
      guinea pig heart and the animals were allowed to recover for 7-9 wk. Thereafter,
      atrial neurons of the intrinsic cardiac plexus were isolated for
      electrophysiological and immunohistochemical analyses. Intracellular voltage
      recordings from intrinsic cardiac neurons demonstrated no significant changes in
      passive membrane properties or action potential configuration compared with age
      matched controls and sham-operated animals. The intrinsic cardiac neurons from
      chronic infarcted hearts did demonstrate an increase in evoked action potential
      (AP) frequency (as determined by the number of APs produced with depolarizing
      stimuli) and an increase in responses to exogenously applied histamine compared
      with sham and age-matched controls. Conversely, pituitary adenylate cyclase
      activating polypeptide (PACAP)-induced increases in intrinsic cardiac neuron
      evoked AP frequency were similar between control and CMI animals.
      Immunohistochemical analysis demonstrated a threefold increase in percentage of
      neurons immunoreactive for neuronal nitric oxide synthase (NOS) in CMI animals
      compared with control and the additional expression of inducible NOS by some
      neurons, which was not evident in control animals. Finally, the density of mast
      cells within the intrinsic cardiac plexus was increased threefold in preparations
      from CMI animals. These results indicate that CMI induces a differential
      remodeling of intrinsic cardiac neurons and functional upregulation of neuronal
      responsiveness to specific neuromodulators.

PMID- 18832085
TI  - Selective estrogen receptor-alpha and estrogen receptor-beta agonists rapidly
      decrease pulmonary artery vasoconstriction by a nitric oxide-dependent mechanism.
AB  - Both endogenous and exogenous estrogen decrease pulmonary artery (PA)
      vasoconstriction. Whether these effects are mediated via estrogen receptor (ER)
      alpha or ER-beta, and whether the contribution of ERs is stimulus-dependent,
      remains unknown. We hypothesized that administration of the selective ER-alpha
      agonist propylpyrazole triol (PPT) and/or the selective ER-beta agonist
      diarylpropiolnitrile (DPN) rapidly decreases PA vasoconstriction induced by
      pharmacologic and hypoxic stimuli via a nitric oxide (NO)-dependent mechanism. PA
      rings (n = 3-10/group) from adult male Sprague-Dawley rats were suspended in
      physiologic organ baths. Force displacement was measured. Vasoconstrictor
      responses to phenylephrine (10(-8)M - 10(-5)M) and hypoxia (Po(2) 35-45 mmHg)
      were determined. Endothelium-dependent and -independent vasorelaxation were
      measured by generating dose-response curves to acetylcholine (10(-8)M - 10(-4)M)
      and sodium nitroprusside (10(-9)M - 10(-5)M). PPT or DPN (10(-9)M - 5 x 10(-5)M)
      were added to the organ bath in the presence and absence of the NO-synthase
      inhibitor N(omega)-nitro-l-arginine methyl ester (l-NAME) (10(-4)M). Selective ER
      alpha activation (PPT, 5 x 10(-5)M) rapidly (<20 min) decreased phenylephrine
      induced vasoconstriction. This effect, as well as PPT's effects on endothelium
      dependent vasorelaxation, were neutralized by l-NAME. In contrast, selective ER
      beta activation (DPN, 5 x 10(-5)M) rapidly decreased phase II of hypoxic
      pulmonary vasoconstriction (HPV). l-NAME eliminated this phenomenon. Lower PPT or
      DPN concentrations were less effective. We conclude that both ER-alpha and ER
      beta decrease PA vasoconstriction. The immediate onset of effect suggests a
      nongenomic mechanism. The contribution of specific ERs appears to be stimulus
      specific, with ER-alpha primarily modulating phenylephrine-induced
      vasoconstriction, and ER-beta inhibiting HPV. NO inhibition eliminates these
      effects, suggesting a central role for NO in mediating the pulmonary vascular
      effects of both ER-alpha and ER-beta.

PMID- 18832086
TI  - Development and characterization of a novel rat model of type 2 diabetes
      mellitus: the UC Davis type 2 diabetes mellitus UCD-T2DM rat.
AB  - The prevalence of type 2 diabetes (T2DM) is increasing, creating a need for T2DM
      animal models for the study of disease pathogenesis, prevention, and treatment.
      The purpose of this project was to develop a rat model of T2DM that more closely
      models the pathophysiology of T2DM in humans. The model was created by crossing
      obese Sprague-Dawley rats with insulin resistance resulting from polygenic adult
      onset obesity with Zucker diabetic fatty-lean rats that have a defect in
      pancreatic beta-cell function but normal leptin signaling. We have characterized
      the model with respect to diabetes incidence; age of onset; longitudinal
      measurements of glucose, insulin, and lipids; and glucose tolerance. Longitudinal
      fasting glucose and insulin data demonstrated progressive hyperglycemia (with
      fasting and fed glucose concentrations >250 and >450 mg/dl, respectively) after
      onset along with hyperinsulinemia resulting from insulin resistance at onset
      followed by a progressive decline in circulating insulin concentrations,
      indicative of beta-cell decompensation. The incidence of diabetes in male and
      female rats was 92 and 43%, respectively, with an average age of onset of 6 mo in
      males and 9.5 mo in females. Results from intravenous glucose tolerance tests,
      pancreas immunohistochemistry, and islet insulin content further support a role
      for beta-cell dysfunction in the pathophysiology of T2DM in this model. Diabetic
      animals also exhibit glycosuria, polyuria, and hyperphagia. Thus diabetes in the
      UC Davis-T2DM rat is more similar to clinical T2DM in humans than in other
      existing rat models and provides a useful model for future studies of the
      pathophysiology, treatment, and prevention of T2DM.

PMID- 18832087
TI  - Enteral nutrients potentiate the intestinotrophic action of glucagon-like peptide
      2 in association with increased insulin-like growth factor-I responses in rats.
AB  - Glucagon-like peptide-2 (GLP-2) is a nutrient-dependent, intestinotrophic hormone
      derived from posttranslational processing of proglucagon in the distal bowel. GLP
      2 is thought to act through indirect mediators, such as IGF-I. We investigated
      whether intestinal expression of GLP-2 and IGF-I system components are increased
      with the mucosal growth induced by enteral nutrient (EN) and/or a low dose of GLP
      2 in parenterally fed rats. Rats were randomized to four treatment groups using a
      2 x 2 design and maintained with parenteral nutrition (PN) for 7 days: PN alone,
      EN, GLP-2, and EN+GLP-2; n = 7-9. The two main treatment effects are +/-GLP-2
      (100 microg.kg body wt(-1).day(-1)) and +/-EN (43% of energy needs, days 4-6).
      Combination treatment with EN+GLP-2 induced synergistic intestinal growth in
      ileum, resulting in greater mucosal cellularity, sucrase segmental activity, and
      gain of body weight (ENxGLP-2, P < 0.04). In addition, EN+GLP-2 induced a
      significant 28% increase in plasma concentration of bioactive GLP-2, a
      significant 102% increase in ileal proglucagon mRNA with no change in ileal
      dipeptidyl peptidase-IV (DPP-IV) specific activity, and significantly reduced
      plasma DPP-IV activity compared with GLP-2. This indicates that EN potentiates
      the intestinotrophic action of GLP-2. Proliferation of enterocytes due to GLP-2
      infusion was associated with greater expression of ileal proglucagon, GLP-2
      receptor, IGF-I, IGF binding protein-3 mRNAs, and greater IGF-I peptide
      concentration in ileum (P < 0.032). Ileal IGF-I mRNA was positively correlated
      with expression of proglucagon, GLP-2R, and IGFBP-5 mRNAs (R2 = 0.43-0.56, P <
      0.0001). Our findings support the hypothesis that IGF-I is one of the downstream
      mediators of GLP-2 action in a physiological model of intestinal growth.

PMID- 18832088
TI  - Leptin inhibits food-deprivation-induced increases in food intake and food
      hoarding.
AB  - Food deprivation stimulates foraging and hoarding and to a much lesser extent,
      food intake in Siberian hamsters. Leptin, the anorexigenic hormone secreted
      primarily from adipocytes, may act in the periphery, the brain, or both to
      inhibit these ingestive behaviors. Therefore, we tested whether leptin given
      either intracerebroventricularly or intraperitoneally, would block food
      deprivation-induced increases in food hoarding, foraging, and intake in animals
      with differing foraging requirements. Hamsters were trained in a running wheel
      based food delivery foraging system coupled with simulated burrow housing. We
      determined the effects of food deprivation and several peripheral doses of leptin
      on plasma leptin concentrations. Hamsters were then food deprived for 48 h and
      given leptin (0, 10, 40, or 80 microg ip), and additional hamsters were food
      deprived for 48 h and given leptin (0, 1.25, 2.5, or 5.0 microg icv). Foraging,
      food intake, and hoarding were measured postinjection. Food deprivation
      stimulated food hoarding to a greater degree and duration than food intake. In
      animals with a foraging requirement, intracerebroventricular leptin almost
      completely blocked food deprivation-induced increased food hoarding and intake,
      but increased foraging. Peripheral leptin treatment was most effective in a
      sedentary control group, completely inhibiting food deprivation-induced increased
      food hoarding and intake at the two highest doses, and did not affect foraging at
      any dose. Thus, the ability of leptin to inhibit food deprivation-induced
      increases in ingestive behaviors differs based on foraging effort (energy
      expenditure) and the route of administration of leptin administration.

PMID- 18832089
TI  - Liver fat, visceral adiposity, and sleep disturbances contribute to the
      development of insulin resistance and glucose intolerance in nondiabetic dialysis
      patients.
AB  - Hemodialysis patients exhibit insulin resistance (IR) in target organs such as
      liver, muscles, and adipose tissue. The aim of this study was to identify
      contributors to IR and to develop a model for predicting glucose intolerance in
      nondiabetic hemodialysis patients. After a 2-h, 75-g oral glucose tolerance test
      (OGTT), 34 hemodialysis patients were divided into groups with normal (NGT) and
      impaired glucose tolerance (IGT). Indices of insulin sensitivity were derived
      from OGTT data. Measurements included liver and muscle fat infiltration and
      central adiposity by computed tomography scans, body composition by dual energy X
      ray absorptiometer, sleep quality by full polysomnography, and functional
      capacity and quality of life (QoL) by a battery of exercise tests and
      questionnaires. Cut-off points, as well as sensitivity and specificity
      calculations were based on IR (insulin sensitivity index by Matsuda) using a
      receiver operator characteristics (ROC) curve analysis. Fifteen patients were
      assigned to the IGT, and 19 subjects to the NGT group. Intrahepatic fat content
      and visceral adiposity were significantly higher in the IGT group. IR indices
      strongly correlated with sleep disturbances, visceral adiposity, functional
      capacity, and QoL. Visceral adiposity, O2 desaturation during sleep, intrahepatic
      fat content, and QoL score fitted into the model for predicting glucose
      intolerance. A ROC curve analysis identified an intrahepatic fat content of >
      3.97% (sensitivity, 100; specificity, 35.7) as the best cutoff point for
      predicting IR. Visceral and intrahepatic fat content, as well as QoL and sleep
      seemed to be involved at some point in the development of glucose intolerance in
      hemodialysis patients. Means of reducing fat depots in the liver and splachnic
      area might prove promising in combating IR and cardiovascular risk in
      hemodialysis patients.

PMID- 18832090
TI  - Effects of high-intensity training on muscle lactate transporters and
      postexercise recovery of muscle lactate and hydrogen ions in women.
AB  - The purpose of this study was to investigate the effects of high-intensity
      interval training (3 days/wk for 5 wk), provoking large changes in muscle lactate
      and pH, on changes in intracellular buffer capacity (betam(in vitro)),
      monocarboxylate transporters (MCTs), and the decrease in muscle lactate and
      hydrogen ions (H+) after exercise in women. Before and after training, biopsies
      of the vastus lateralis were obtained at rest and immediately after and 60 s
      after 45 s of exercise at 190% of maximal O2 uptake. Muscle samples were analyzed
      for ATP, phosphocreatine (PCr), lactate, and H+; MCT1 and MCT4 relative abundance
      and betam(in vitro) were also determined in resting muscle only. Training
      provoked a large decrease in postexercise muscle pH (pH 6.81). After training,
      there was a significant decrease in betam(in vitro) (-11%) and no significant
      change in relative abundance of MCT1 (96 +/- 12%) or MCT4 (120 +/- 21%). During
      the 60-s recovery after exercise, training was associated with no change in the
      decrease in muscle lactate, a significantly smaller decrease in muscle H+, and
      increased PCr resynthesis. These results suggest that increases in betam(in
      vitro) and MCT relative abundance are not linked to the degree of muscle lactate
      and H+ accumulation during training. Furthermore, training that is very intense
      may actually lead to decreases in betam(in vitro). The smaller postexercise
      decrease in muscle H+ after training is a further novel finding and suggests that
      training that results in a decrease in H+ accumulation and an increase in PCr
      resynthesis can actually reduce the decrease in muscle H+ during the recovery
      from supramaximal exercise.

PMID- 18832091
TI  - Hypertonic saline reduces neutrophil-epithelial interactions in vitro and gut
      tissue damage in a mouse model of colitis.
AB  - Transepithelial migration of polymorphonuclear neutrophils (PMN) plays a crucial
      role in inflammatory conditions of the intestine, such as inflammatory bowel
      diseases. Hypertonic saline (HS) exerts various inhibitory effects on PMN
      function. We hypothesized that HS could inhibit transepithelial migration of PMN
      and thereby prevent inflammatory events in experimental colitis. Isolated human
      PMN were treated with HS (40 mM), and their transmigration across a monolayer of
      T84 epithelial cells was induced by N-formyl-methionyl-leucyl-phenylalanine.
      Monolayer disruption was assessed by monitoring changes in transepithelial
      conductance in an Ussing chamber. Colitis in mice was induced by oral
      administration of dextran sulfate sodium (DSS). Animals were treated with 4 or 8
      ml/kg of 7.5% saline intraperitoneally two times daily for 7 days. Controls
      received equivalent volumes of normal saline (NS, n = 6) or no intraperitoneal
      treatment (DSS, n = 12). The severity of inflammation was evaluated based on
      disease activity index and histology score. HS treatment of PMN in vitro
      significantly reduced cell migration and the disruption of T84 monolayers
      compared with untreated control cells (n = 5, P < 0.05). This effect of HS was
      dose dependent. HS treatment in vivo also reduced colitis-induced gut tissue
      damage, as indicated by an improved histology score compared with the NS and DSS
      groups. We conclude that HS inhibits transepithelial migration of PMN in vitro
      and gut tissue damage in vivo in a mouse model of colitis. Thus HS may have
      clinical value to reduce PMN-mediated intestinal damage.

PMID- 18832092
TI  - Changes in hemodynamic and neurohumoral control cause cardiac damage in one
      kidney, one-clip hypertensive mice.
AB  - Sympathovagal balance and baroreflex control of heart rate (HR) were evaluated
      during the development (1 and 4 wk) of one-kidney, one-clip (1K1C) hypertension
      in conscious mice. The development of cardiac hypertrophy and fibrosis was also
      examined. Overall variability of systolic arterial pressure (AP) and HR in the
      time domain and baroreflex sensitivity were calculated from basal recordings.
      Methyl atropine and propranolol allowed the evaluation of the sympathovagal
      balance to the heart and the intrinsic HR. Staining of renal ANG II in the kidney
      and plasma renin activity (PRA) were also evaluated. One and four weeks after
      clipping, the mice were hypertensive and tachycardic, and they exhibited elevated
      sympathetic and reduced vagal tone. The intrinsic HR was elevated only 1 wk after
      clipping. Systolic AP variability was elevated, while HR variability and
      baroreflex sensitivity were reduced 1 and 4 wk after clipping. Renal ANG II
      staining and PRA were elevated only 1 wk after clipping. Concentric cardiac
      hypertrophy was observed at 1 and 4 wk, while cardiac fibrosis was observed only
      at 4 wk after clipping. In conclusion, these data further support previous
      findings in the literature and provide new features of neurohumoral changes
      during the development of 1K1C hypertension in mice. In addition, the 1K1C
      hypertensive model in mice can be an important tool for studies evaluating the
      role of specific genes relating to dependent and nondependent ANG II hypertension
      in transgenic mice.

PMID- 18832093
TI  - HIF-1alpha protein rather than mRNA as a marker of hypoxia in adipose tissue in
      obesity: focus on "inflammation is associated with a decrease of lipogenic
      factors in omental fat in women," by Poulain-Godefroy et al.

PMID- 18832095
TI  - 17 beta-estradiol modulates expression of low-voltage-activated Ca(V)3.2 T-type
      calcium channel via extracellularly regulated kinase pathway in cardiomyocytes.
AB  - T-type Ca(2+) channel current (I(Ca,T)) plays an important role for spontaneous
      pacemaker activity and is involved in the progression of structural heart
      diseases. Estrogens are of importance for the regulation of growth and
      differentiation and function in a wide array of target tissues, including those
      in the cardiovascular system. The aim of this study was to elucidate the short
      term and long-term effects of 17beta-estradiol (E(2)) on I(Ca,T) in
      cardiomyocytes. We employed in vivo and in vitro techniques to clarify E(2)
      mediated modulation of heart rate (HR) in ovariectomized rats and I(Ca,T) in
      cardiomyocytes. Ovariectomy increased HR and E(2) supplement reduced HR in
      ovariectomized rats. Slowing of E(2)-induced HR was consistent with the
      deceleration of automaticity in E(2)-treated neonatal cardiomyocytes. Short-term
      application of E(2) did not have significant effects on I(Ca,T), whereas in
      cardiomyocytes treated with 10 nm E(2) for 24 h, estrogen receptor-independent
      down-regulation of peak I(Ca,T) and declination of Ca(V)3.2 mRNA were observed.
      Expression of a cardiac-specific transcription factor Csx/Nkx2.5 was also
      suppressed by E(2) treatment for 24 h. On the other hand, expression of Ca(V)3.1
      mRNA was unaltered by E(2) treatment in this study. An ERK-1/2, 5 inhibitor, PD
      98059, abolished the effects of E(2) on I(Ca,T) and Ca(V)3.2 mRNA as well as
      Csx/Nkx2.5 mRNA. These findings indicate that E(2) decreases Ca(V)3.2 I(Ca,T)
      through activation of ERK-1/2, 5, which is mediated by the suppression of
      Csx/Nkx2.5-dependent transcription, suggesting a genomic effect of E(2) as a
      negative chronotropic factor in the heart.

PMID- 18832096
TI  - Regulation of P450c17 expression in the early embryo depends on GATA factors.
AB  - The enzyme P450c17 is required for glucocorticoid, sex steroid, and some
      neurosteroid biosynthesis. Defective human P450c17 causes sexual infantilism and
      46,XY sex reversal but is compatible with life, whereas ablation of the
      corresponding mouse gene causes embryonic lethality at around E7. Normal mouse
      embryos express P450c17 protein and activity in the embryonic endoderm at E7.
      Adult adrenal and gonadal steroidogenesis requires steroidogenic factor-1 (SF-1),
      but SF-1 is not expressed in the early mouse embryo. We show that P450c17 is
      expressed in differentiated mouse parietal and visceral endoderm lineages, in
      cultured mouse F9 embryonic carcinoma stem cells, in mouse embryonic stem cells,
      and in cultured mouse P19 stem cells. Bases -110 to -55 (which contain an SF-1
      site and two potential GATA sites) of the rat cyp17 gene confer promoter activity
      in F9 cells. Overexpression of SF-1 has no effect, whereas overexpression of
      GATA4 in F9 cells increases transcription from -110/-55 fused to a reporter and
      increases endogenous P450c17 mRNA. Chromatin immunoprecipitation assays show that
      GATA4 binds to -215/+55 of mouse cyp17. Stimulating F9 cells with retinoic acid
      and cAMP differentiates them into visceral and parietal endoderm. Commensurate
      with cell differentiation, quantitative PCR showed increased GATA4 and GATA6
      mRNAs, temporally followed by increased P450c17 mRNA. Small interfering RNA
      inhibition of GATA4 or GATA6 in undifferentiated or differentiated F9 cells
      diminished endogenous cyp17 expression. Thus, P450c17 is expressed in mouse
      embryonic stem cells, its expression increases upon differentiation to an early
      embryonic endoderm lineage, and GATA4/6 are responsible for activation of P450c17
      gene expression at this early stage of embryonic development.

PMID- 18832097
TI  - Inactivation of the human vitamin D receptor by caspase-3.
AB  - Calcitriol actions are mediated by the vitamin D receptor (VDR), a nuclear
      transcription factor of the steroid-retinoid-thyroid nuclear receptor gene
      superfamily. Calcitriol inhibits the growth of many cells including cancer cells
      by inducing cell cycle arrest. In some cancer cell lines, calcitriol also induces
      apoptosis. In the LNCaP prostate cancer cell line, induction of apoptosis and
      caspase-3/7 activities by staurosporine (STS) abolished [(3)H]1,25-dihydroxy
      vitamin D(3) binding and VDR protein, suggesting that the VDR may be targeted for
      inactivation by caspases during apoptosis. A potential caspase-3 site
      (D(195)MMD(198)S) was identified in the human VDR ligand-binding domain.
      Mutations D195A, D198A, and S199A were generated in the putative capase-3
      cleavage site. In transfected COS-7 cells, STS treatment resulted in the cleavage
      of the wild-type (WT) VDR and S199A mutant VDR but not the D195A or D198A
      mutants. In in vitro assays, the WT VDR and S199A mutant VDR were cleaved by
      caspase-3, although the D195A and D198A mutants were resistant to caspase-3. In
      vitro, the WT VDR was also cleaved by caspase-6 and caspase-7 and in extracts of
      STS-treated LNCaP cells. In STS-treated LNCaP cells and human skin fibroblasts,
      the proteasome inhibitor MG-132 protected the VDR caspase cleavage fragment from
      further degradation by the 26S proteasome. The rat VDR that does not contain the
      caspase-3 cleavage site was not cleaved in STS-treated COS-7 cells. In
      conclusion, our results demonstrate that the human VDR is a target of caspase-3
      and suggest that activation of caspase-3 may limit VDR activity.

PMID- 18832098
TI  - Psychosocial stress inhibits amplitude of gonadotropin-releasing hormone pulses
      independent of cortisol action on the type II glucocorticoid receptor.
AB  - Our laboratory has developed a paradigm of psychosocial stress (sequential
      layering of isolation, blindfold, and predator cues) that robustly elevates
      cortisol secretion and decreases LH pulse amplitude in ovariectomized ewes. This
      decrease in LH pulse amplitude is due, at least in part, to a reduction in
      pituitary responsiveness to GnRH, caused by cortisol acting via the type II
      glucocorticoid receptor (GR). The first experiment of the current study aimed to
      determine whether this layered psychosocial stress also inhibits pulsatile GnRH
      release into pituitary portal blood. The stress paradigm significantly reduced
      GnRH pulse amplitude compared with nonstressed ovariectomized ewes. The second
      experiment tested if this stress-induced decrease in GnRH pulse amplitude is
      mediated by cortisol action on the type II GR. Ovariectomized ewes were allocated
      to three groups: nonstress control, stress, and stress plus the type II GR
      antagonist RU486. The layered psychosocial stress paradigm decreased GnRH and LH
      pulse amplitude compared with nonstress controls. Importantly, the stress also
      lowered GnRH pulse amplitude to a comparable extent in ewes in which cortisol
      action via the type II GR was antagonized. Therefore, we conclude that
      psychosocial stress reduces the amplitude of GnRH pulses independent of cortisol
      action on the type II GR. The present findings, combined with our recent
      observations, suggest that the mechanisms by which psychosocial stress inhibits
      reproductive neuroendocrine activity at the hypothalamic and pituitary levels are
      fundamentally different.

PMID- 18832099
TI  - Estrogen receptor-alpha mediates the epidermal growth factor-stimulated prolactin
      expression and release in lactotrophs.
AB  - Epidermal growth factor (EGF) is a potent regulator of cell function in many cell
      types. EGF-receptor (EGFR/ErbB1)-activated Erk1/2 has been reported to activate
      estrogen receptor (ER) in an estrogen (E2)-independent manner. In the pituitary
      lactotrophs, both EGF and E2 stimulate prolactin (PRL) release, but the nature of
      interactions between ErbB and ERalpha signaling is unknown. Our objectives were
      to 1) characterize EGF-induced PRL release, 2) determine whether this effect
      requires ERalpha, and 3) determine the molecular basis for cross talk between
      ErbB and ERalpha signaling pathways. Using GH3 cells, a rat lactotroph cell line,
      we report that EGF stimulates PRL gene expression and release in a dose- and time
      dependent manner. EGF caused a rapid and robust activation of Erk1/2 via ErbB1
      and induced phosphorylation of S118 on ERalpha in an Erk1/2-dependent manner. The
      global antiestrogen ICI 182780 and the ERalpha-specific antagonist 1,3-bis(4
      hydroxyphenyl)-4-methyl-5-[4-(2-piperidinylet hoxy)phenol]-1H-pyrazole
      dihydrochloride (MPP), but not the ERbeta-specific antagonist 4-[2-Phenyl-5,7
      bis(trifluoromethyl) pyrazolo[1,5-a]pyrimidin-3-yl]phenol (PHTPP), blocked the
      EGF-induced PRL release, indicating an ERalpha requirement. This was further
      supported by using ERalpha knockdown by small interfering RNA. Because the
      antiestrogens did not block EGF-induced Mek-1 or Erk1/2 phosphorylation, ERalpha
      is placed downstream from the ErbB1-activated Erk1/2. These results provide the
      first evidence that ErbB1-induced PRL release is ERalpha dependent.

PMID- 18832100
TI  - Oxytocin receptor down-regulation is not necessary for reducing oxytocin-induced
      prostaglandin F(2alpha) accumulation by interferon-tau in a bovine endometrial
      epithelial cell line.
AB  - Interferon-tau (IFNtau) is the embryonic signal responsible for pregnancy
      recognition in ruminants. The primary action of IFNtau is believed to be mediated
      through inhibition of prostaglandin F(2alpha) (PGF(2alpha)) released from the
      endometrial epithelial cells in response to oxytocin (OT). Our working hypothesis
      was that the antiluteolytic effect of IFNtau also involved modulation of PG
      production downstream of OT receptor (OTR) and/or cyclooxygenase 2 (COX2). There
      is currently no OT-sensitive endometrial cell line to study the molecular
      mechanisms underlying our hypotheses. Therefore, we established an immortalized
      bovine endometrial epithelial cell line (bEEL) exhibiting OT response. These
      cells were cytokeratin positive, expressed steroid receptors, and exhibited
      preferential accumulation of PGF(2alpha) over PGE(2). The bEEL cells were highly
      sensitive to OT, showing time- and concentration-dependent increase in COX2
      transcript and protein and PGF(2alpha) accumulation. Interestingly, IFNtau (20
      ng/ml) significantly reduced OT-induced PGF(2alpha) accumulation, but
      surprisingly, the effect was not mediated through down-regulation of either OTR
      or COX2. Rather, IFNtau up-regulated COX2 in a time- and concentration-dependent
      manner while decreasing OT-induced PG accumulation. This suggests that COX2 is
      not a primary target for the antiluteolytic effect of IFNtau. Because IFNtau
      reduced OT-stimulated PGF(2alpha) accumulation within 3 h, the mechanism likely
      involves a direct interference at the level of the OT signaling or transcription
      in addition to the down-regulation of OTR observed in vivo. In summary, bEEL
      cells offer a unique in vitro model for investigating the cellular and molecular
      mechanisms underlying OT and IFNtau response in relation with luteolysis and
      recognition of pregnancy in the bovine.

PMID- 18832101
TI  - Parathyroid hormone contributes to regulating milk calcium content and modulates
      neonatal bone formation cooperatively with calcium.
AB  - To determine whether PTH and calcium (Ca) interact in neonatal bone formation,
      female lactating mice either heterozygous (PTH(+/-)) or homozygous (PTH(-/-)) for
      targeted deletion of the pth gene were fed either a normal (1% Ca, 0.6%
      phosphate) or high-Ca diet (2% Ca and 0.4% phosphate). Dietary effects on milk Ca
      content and Ca-regulating hormones were determined in dams, and the effects of
      milk content were assessed on bone turnover in 3-wk-old pups. On the normal diet,
      milk Ca and 1,25-dihydroxyvitamin D(3) levels were lower, but milk PTH-related
      protein levels were higher in the PTH(-/-) dams compared with the PTH(+/-) dams.
      On the high-Ca diet, milk Ca levels were higher, but milk 1,25-dihydroxyvitamin
      D(3) and PTH-related protein levels were lower in both PTH(+/-) and PTH(-/-)
      dams. In pups fed by PTH(-/-) dams compared with pups fed by PTH(+/-) dams on
      normal diets, bone mineral density, trabecular bone volume relative to tissue
      volume, and the number of osteoblasts were reduced in both PTH(+/-) (32.5 +/- 1.2
      vs. 39.6 +/- 1.5 mg/cm(2), P < 0.05; 23.3 +/- 1.6 vs. 29.2 +/- 2.8%, P < 0.01;
      and 94.2 +/- 8.2 vs. 123.5 +/- 3.5/mm(2), P < 0.01, respectively) and PTH(-/-)
      (20.4 +/- 0.9 vs. 27.0 +/- 1.2 mg/mm(2), P < 0.05; 16.8 +/- 1.9 vs. 19.3 +/-
      2.1%, P < 0.05; and 48.6 +/- 7.9 vs. 90.5 +/- 8.6/mm(2), P < 0.01, respectively)
      pups but were lower in the PTH(-/-) pups compared with the PTH(+/-) pups. In
      contrast, in pups fed by either PTH(+/-) or PTH(-/-) dams on the high-Ca diet,
      bone mineral density, bone volume/tissue volume, and osteoblast numbers were
      significantly higher, in both PTH(+/-) (50.5 +/- 1.7 vs. 58.7 +/- 2.0 mg/mm(2), P
      < 0.05; 37.9 +/- 5.2 vs. 46.1 +/- 5.1, P < 0.05; and 120.5 +/- 9.2 vs. 159.3 +/-
      14.7/mm(2), P < 0.01, respectively) and PTH(-/-) (33.0 +/- 1.2 vs. 47.5 +/- 2.2
      mg/mm(2), P < 0.001; 23.8 +/- 3.1 vs. 35.9 +/- 2.0, P < 0.05; and 78.7 +/- 10.1
      vs. 99.8 +/- 13.6/mm(2), P < 0.05, respectively), and were highest in the PTH(+/
      ) pups fed by the PTH(+/-) dams on the high-Ca diet. These results indicate that
      PTH can modulate Ca content of milk, and that PTH and Ca can each exert
      cooperative roles on osteoblastic bone formation in the neonate.

PMID- 18832102
TI  - Expression of scavenger receptor-BI and low-density lipoprotein receptor and
      differential use of lipoproteins to support early steroidogenesis in luteinizing
      macaque granulosa cells.
AB  - An ovulatory hCG stimulus to rhesus macaques undergoing controlled ovarian
      stimulation protocols results in a rapid and sustained increase in progesterone
      synthesis. The use of lipoproteins as a substrate for progesterone synthesis
      remains unclear, and the expression of lipoprotein receptors [very-low-density
      lipoprotein receptor (VLDLR), low-density lipoprotein receptor (LDLR), and
      scavenger receptor-BI (SR-BI)] soon after human chorionic gonadotropin (hCG) (<12
      h) has not been characterized. This study investigated lipoprotein receptor
      expression and lipoprotein (VLDL, LDL, and HDL) support of steroidogenesis during
      luteinization of macaque granulosa cells. Granulosa cells were aspirated from
      rhesus monkeys undergoing controlled ovarian stimulation before or up to 24 h
      after an ovulatory hCG stimulus. The expression of VLDLR decreased within 3 h of
      hCG, whereas LDLR and SR-BI increased at 3 and 12 h, respectively. Granulosa
      cells isolated before hCG were cultured for 24 h in the presence of FSH or FSH
      plus hCG with or without VLDL, LDL, or HDL. Progesterone levels increased in the
      presence of hCG regardless of lipoprotein addition, although LDL, but not HDL,
      further augmented hCG-induced progesterone. Other cells were cultured with FSH or
      FSH plus hCG without an exogenous source of lipoprotein for 24 h, followed by an
      additional 24 h culture with or without lipoproteins. Cells treated with hCG in
      the absence of any lipoprotein were unable to maintain progesterone levels
      through 48 h, whereas LDL (but not HDL) sustained progesterone synthesis. These
      data suggest that an ovulatory stimulus rapidly mobilizes stored cholesterol
      esters for use as a progesterone substrate and that as these are depleted, new
      cholesterol esters are obtained through an LDLR- and/or SR-BI-mediated mechanism.

PMID- 18832103
TI  - Basigin-mediated gene expression changes in mouse uterine stromal cells during
      implantation.
AB  - Implantation of mouse embryos is dependent on the proliferation and
      differentiation of uterine stromal cells in a process called decidualization.
      Decidualization both supports and limits the invasion of the implanting embryo
      and is regulated in part by the expression of matrix metalloproteinases (MMPs)
      and their inhibitors, the tissue inhibitors of metalloproteinases (TIMPs).
      Molecules that alter the balance between MMP and TIMP expression could prevent
      implantation of the embryo. The membrane glycoprotein basigin (CD147/EMMPRIN), a
      known inducer of MMPs, is necessary for normal implantation in the mouse. The
      purpose of this study was to investigate the potential roles of basigin during
      implantation in the mouse. Using an in vitro stromal cell culture system, we
      found that recombinant human basigin protein (rBSG) increases MMP-3 and MMP-9
      expression without altering TIMP-3 expression. Our results also showed rBSG
      induces expression of cytokines IL-1alpha/beta and leukocyte chemoattractants,
      CCL3, CCL20, CXCL2, and CXCL5. More importantly, rBSG significantly suppressed
      stromal cell decidualization as shown by the inhibition of alkaline phosphatase-2
      expression and activity by rBSG. However, rBSG did not affect stromal cell
      proliferation. Taken together, our data indicate that basigin mediates gene
      expression changes in mouse uterine stromal cells and suggests that temporal and
      spatial regulation of basigin expression may be involved in the recruitment of
      leukocytes to the mouse uterus during early pregnancy.

PMID- 18832104
TI  - Bone morphogenetic protein-2 antagonizes renal interstitial fibrosis by promoting
      catabolism of type I transforming growth factor-beta receptors.
AB  - TGF-beta is a therapeutic target for renal fibrosis. Scientists have long sought
      ways to antagonize TGF-beta to ameliorate diabetic nephropathy. Bone
      morphogenetic protein (BMP-2) is a member of the TGF-beta superfamily and is
      highly regulated in the kidney. Thus, the role of BMP-2 was investigated in NRK
      49F cells (rat fibroblasts). We showed that TGF-beta1 induces an increase in
      fibronectin. Treatment with exogenous BMP-2 or pCMV-BMP-2 significantly reversed
      the TGF-beta1-induced increase in fibronectin concomitant with a significant
      decrease in type I TGF-beta receptors (TGF-beta RI). Moreover, BMP-2
      significantly shortened the half-life of TGF-beta RI. These results are related
      to proteosomal activation because MG132, a proteasome inhibitor, abolished BMP-2
      mediated degradation of TGF-beta RI. This was confirmed because BMP-2 time course
      dependently enhanced the ubiquitination level of TGF-beta RI. In addition, Smads
      would seem to be involved in the interaction of BMP-2 and TGF-beta. We
      demonstrated that BMP-2 significantly reversed the TGF-beta1-induced increase in
      pSmad2/3 and reversed the TGF-beta1-induced decrease in inhibitory Smad7. Most
      importantly, Smad7 small interfering RNA abolished the BMP-2-induced decrease in
      TGF-beta RI. We evaluated the clinical efficacy of BMP-2 using unilateral
      ureteral obstruction rats. BMP-2 was administered ip for 7 d. In the unilateral
      ureteral obstruction kidneys, interstitial fibrosis was prominent. However,
      treatment with BMP-2 dramatically reduced Masson's trichrome staining (collagen)
      in the interstitial and tubular areas of the kidneys concomitantly with a
      reduction in TGF-beta RI. These results suggest that BMP-2 acts as a novel
      fibrosis antagonizing cytokine partly by down-regulating TGF-beta RI and Smads.

PMID- 18832105
TI  - Utility and limitations of a multicenter nocturnal home hemodialysis cohort.
AB  - Nocturnal home hemodialysis (NHD) is the most intensive dialysis strategy among
      dialytic renal replacement options and is receiving increased attention as more
      research reveals its physiologic restorative potential compared with conventional
      hemodialysis; however, a significant gap in knowledge remains concerning the
      predictors of program success and the clinical outcomes of NHD. This review aims
      to highlight the methodologic strengths and pitfalls of various study designs as
      they pertain to NHD research and lays the foundation for the CANandian Slow Long
      nightly ExtEnded dialysis Programs (CAN-SLEEP), a multicenter NHD research
      network aimed to facilitate investigation of NHD.

PMID- 18832107
TI  - A survey of nephrologists' views on preemptive transplantation.
AB  - BACKGROUND AND OBJECTIVES: Despite emerging evidence that preemptive
      transplantation is the best treatment modality for patients reaching end-stage
      renal disease (ESRD), it is underutilized. Nephrologists' views on preemptive
      transplantation are explored herein. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: A web-based survey elicited barriers to preemptive transplantation
      as perceived by nephrologists as well as demographic and practice variables
      associated with a favorable attitude toward preemptive transplantation. RESULTS:
      Four hundred seventy-six of 5,901 eligible nephrologists responded (8%
      participation rate). Seventy-one percent of respondents agreed that preemptive
      transplantation is the best treatment modality for eligible chronic kidney
      disease (CKD) patients reaching ESRD, 69% reported that late referrals did not
      allow enough time for patients to be evaluated for preemptive transplantation,
      and 50% stated that there was too much delay between a patient's referral and the
      time the patient was seen at the transplant center. Nephrologists agreed to a
      lesser extent that they should be held accountable for CKD patients' education
      (26%) and preemptive transplant referrals (23%). The most important patient
      factors considered when deciding not to discuss preemptive transplant were poor
      health status (70%), lack of compliance (69%), other medical problems (51%),
      being too old (40%), lack of prescription coverage (37%), and lack of health
      insurance to cover the costs of the procedure (36%). CONCLUSIONS: Surveyed
      nephrologists consider preemptive transplantation as the optimal treatment
      modality for eligible patients. Late referral, patient health and insurance
      status, and delayed transplant center evaluation are perceived as major barriers
      to preemptive transplantation.

PMID- 18832106
TI  - Biomarkers and health-related quality of life in end-stage renal disease: a
      systematic review.
AB  - BACKGROUND AND OBJECTIVES: Health-related quality of life (HRQOL) predicts
      mortality in ESRD, yet adoption of HRQOL monitoring is not widespread, and
      regulatory authorities remain predominantly concerned with monitoring traditional
      biologic parameters. To assist with future efforts to adopt HRQOL monitoring
      while acknowledging the importance of biomarkers, this study sought to establish
      which domains of HRQOL are most affected by ESRD and to measure the strength of
      evidence linking common biomarkers to HRQOL in ESRD. DESIGN, SETTING,
      PARTICIPANTS, & MEASUREMENTS: A systematic review was performed to identify
      studies that measured HRQOL in ESRD. Data were abstracted according to a
      conceptual model regarding the measurement of HRQOL differences, and HRQOL data
      were converted to weighted mean effect sizes and correlation coefficients.
      RESULTS: The impact of ESRD was largest in the Short Form 36 domains of physical
      functioning (e.g., role-physical, vitality) and smallest in mental functioning
      (e.g., mental health, role-emotional). Dialysis adequacy, as measured by Kt/V,
      was a poor correlate for Short Form 36 scores. Similarly, mineral metabolism
      (e.g., calcium x phosphorous, parathyroid hormone) and inflammatory (e.g., C
      reactive protein, TNF) biomarkers had small effect sizes and correlations with
      HRQOL. In contrast, hematocrit demonstrated small to moderate relationships with
      mental and physical HRQOL, and nutritional biomarkers (e.g., albumin, creatinine,
      body mass index) demonstrated moderate to large relationships. CONCLUSIONS: HRQOL
      in ESRD is most affected in the physical domains, and nutritional biomarkers are
      most closely associated with these domains. In contrast, Kt/V, mineral metabolism
      indices, and inflammatory markers are poor HRQOL correlates.

PMID- 18832108
TI  - Risperidone attenuates local and systemic inflammatory responses to ameliorate
      diet-induced severe necrotic pancreatitis in mice: it may provide a new therapy
      for acute pancreatitis.
AB  - In a previous article, we showed that a potent serotonin-, 5-hydroxytryptamine-2A
      (5-HT(2A)) antagonist, risperidone, ameliorated cerulein-induced edematous
      pancreatitis in mice. In the present article, young female mice were fed a
      choline-deficient, ethionine-supplemented diet. All of the mice developed severe
      necrotic pancreatitis, and approximately 50% of them died within 4 days. Serum
      levels of proinflammatory interleukin (IL)-6 significantly increased on day 3 and
      returned toward the control on day 4 of choline-deficient ethionine-supplemented
      (CDE) diet treatment. The time course of IL-6 levels paralleled those of plasma
      amylase and lipase activities. On the other hand, platelet counts significantly
      decreased on day 3, and the change became more marked on day 4, coinciding with
      mortality and histological alterations of the pancreas (edema, inflammatory cell
      infiltration, necrosis). Preceding these changes, plasma levels of 5
      hydroxyindoleacetic acid (5-HIAA) increased on feeding a CDE diet to reach a peak
      on day 3 and returned toward the control on day 4. Risperidone (0.1-3.2 mg/kg
      twice a day) hardly affected the 5-HIAA levels but dose-dependently attenuated
      the serum IL-6 levels, plasma amylase/lipase levels, platelet counts,
      histological alterations, and mortality of diet-induced pancreatitis mice. These
      results are discussed in relation to the pathogenesis of acute pancreatitis.
      Thus, we speculate that acinar cell injury triggers local inflammatory reactions
      and, if coincided with enhanced IL-6 release, leads to a systemic inflammatory
      response syndrome, which is responsible for the mortality. In addition, it is
      suggested that diet-induced 5-HT release and 5-HT(2A) receptor activation are
      involved in this whole process of pancreatitis development. Risperidone may
      provide a new therapy for the disease.

PMID- 18832109
TI  - Primary care physicians' evaluation and treatment of depression: Results of an
      experimental study using video vignettes.
AB  - Little is known about how patient and primary care physician characteristics are
      associated with quality of depression care. The authors conducted structured
      interviews of 404 randomly selected primary care physicians after their
      interaction with CD-ROM vignettes of actors portraying depressed patients.
      Vignettes varied along the dimensions of medical comorbidity, attributions
      regarding the cause of depression, style, race/ethnicity, and gender. Results
      show that physicians showed wide variation in treatment decisions; for example,
      most did not inquire about suicidal ideation, and most did not state that they
      would inform the patient that there can be a delay before an antidepressant is
      therapeutic. Several physician characteristics were significantly associated with
      management decisions. Notably, physician age was inversely correlated with a
      number of quality-of-care measures. In conclusion, quality of care varies among
      primary care physicians and appears to be associated with physician
      characteristics to a greater extent than patient characteristics.

PMID- 18832110
TI  - Children's and adolescents' use of mental health care is a family matter.
AB  - This article discusses the influence of family structure on children's use of
      mental health services and explores whether a family's dependency on government
      assistance compensates for the effect of family income on children's use of
      services. Children in nontraditional families are at greater risk of using mental
      health services and have more mental health visits. Family participation in
      government subsidies programs offsets the influence of family income on the use
      of mental health services.

PMID- 18832111
TI  - Y chromosome haplotype analysis in Portuguese cattle breeds using SNPs and STRs.
AB  - DNA samples from 307 males of 13 Portuguese native cattle breeds, 57 males of the
      3 major exotic breeds in Portugal (Charolais, Friesian, and Limousin), and 5
      Brahman (Bos indicus) were tested for 5 single nucleotide polymorphisms, 1
      "indel," and 7 microsatellites specific to the Y chromosome. The 13 Y-haplotypes
      defined included 3 previously described patrilines (Y1, Y2, and Y3) and 10 new
      haplotypes within Bos taurus. Native cattle contained most of the diversity with
      7 haplotypes (H2Y1, H3Y1, H5Y1, H7Y2, H8Y2, H10Y2, and H12Y2) found only in these
      breeds. H6Y2 and H11Y2 occurred in high frequency across breeds including the
      exotics. Introgression of Friesian cattle into Ramo Grande was inferred through
      their sharing of haplotype H4Y1. Among the native breeds, Mertolenga had the
      highest haplotype diversity (0.68 +/- 0.07), Brava de Lide was the least
      differentiated. The analyses of molecular variance showed significant (P <
      0.0001) differences between breeds with more than 64% of the total genetic
      variation found among breeds within groups and 33-35% within breeds. The
      detection of INRA189-104 allele in 8 native breeds suggested influence of African
      cattle in breeds of the Iberian Peninsula. The presence in Portuguese breeds of
      Y1 patrilines, also found in aurochs, could represent more ancient local
      haplotypes.

PMID- 18832112
TI  - Unparalleled contribution of 18F-FDG PET to medicine over 3 decades.

PMID- 18832119
TI  - Ensuring the future of nuclear medicine and molecular imaging.

PMID- 18832120
TI  - Reproducibility of tumor blood flow quantification with 15O-water PET.
AB  - Noninvasive methods for quantifying tumor blood flow (TBF) have a potentially
      important role in the field of drug development. (15)O-water PET has been used in
      several studies aimed at monitoring response to novel treatments. Assessing the
      significance of changes in TBF requires knowledge of the reproducibility of the
      technique. This article quantifies the reproducibility of the (15)O-water
      technique for TBF applications. METHODS: A total of 43 pairs of replicate (15)O
      water studies were performed on 23 different patients with cancer. TBF was
      estimated using a standard, single-compartment model, and the replicate data were
      used to assess the reproducibility of the method. RESULTS: The magnitude of the
      differences between replicate flow measurements was found to be proportional to
      their means. TBF was measured with a within-subject coefficient of variation of
      13.4% and a repeatability of 37.1%. The volume of distribution was measured with
      a within-subject coefficient of variation of 8.6% and a repeatability of 24.0%.
      CONCLUSION: (15)O-water PET can be used to measure TBF with a reproducibility
      that is consistent with other applications of the technique. The short half-life
      of the isotope permits multiple replicate studies to be performed during the same
      imaging session, allowing the reproducibility of the average flow estimate to be
      adapted to the required task. (15)O-water PET is a powerful and robust tool for
      TBF quantification.

PMID- 18832121
TI  - Comparative study of selective chromogenic (chromID VRE) and bile esculin agars
      for isolation and identification of vanB-containing vancomycin-resistant
      enterococci from feces and rectal swabs.
AB  - The new chromogenic agar chromID VRE (cIDVRE; bioMerieux) was compared with bile
      esculin agar (BD) containing 6 mg/liter vancomycin for the detection of
      colonization with vanB-containing vancomycin-resistant enterococci (VRE). At 48 h
      of incubation, the results obtained with both media were comparable. However,
      cIDVRE detected significantly more VRE at 24 h (39.3% versus 21.3%, P = 0.003),
      and its use may facilitate the timely implementation of infection control
      procedures.

PMID- 18832122
TI  - Pyogenic flexor tenosynovitis associated with Cellulosimicrobium cellulans.
AB  - Cellulosimicrobium cellulans, formerly known as Oerskovia xanthineolytica, is a
      rare human pathogen, often in association with a foreign body. A case of pyogenic
      flexor tenosynovitis associated with C. cellulans in an immunocompetent boy is
      described, underlining the importance of prompt surgical and microbiologic
      evaluation.

PMID- 18832123
TI  - Extreme genetic diversity of methicillin-resistant Staphylococcus epidermidis
      strains disseminated among healthy Japanese children.
AB  - For the past few years, we have been observing the dissemination of methicillin
      resistant staphylococci in the community. From 2001 to 2003, an evaluation of
      nasal samples from 1,285 children in five day-care centers and two kindergartens
      in three districts in Japan revealed that methicillin-resistant coagulase
      negative staphylococci (MRC-NS) have been widely disseminated in the Japanese
      community. Their prevalence is much greater than community-acquired methicillin
      resistant Staphylococcus aureus (CA-MRSA). Forty-nine children (3.81%) were
      colonized with MRSA, whereas 390 children (30.35%) were colonized with MRC-NS.
      These MRC-NS strains predominantly harbored a pair of cassette chromosome
      recombinase types A2 and B2 (ccrAB2). Of these, 40.8% harbored type IVa
      staphylococcal cassette chromosome mec (SCCmec) elements, a
      distinct/characteristic type of SCCmec in pandemic clones of CA-MRSA.
      Interestingly, there was also a high frequency of nontypeable strains which
      possessed atypical structures compared to previous SCCmec types. Among the MRC
      NS, the majority of strains (63.59%) were methicillin-resistant Staphylococcus
      epidermidis (MRSE). Their genotypes, as judged from pulsed-field gel
      electrophoresis (PFGE), were highly diverse. They were so diverse that there was
      no sign of an immediate transmission of any MRSE clone among children in the same
      institutions. In a previous report, we expounded that a few CA-MRSA clones with
      distinct SCCmec types were disseminated among children in the same institutions.
      Au contraire, with the case of CA-MRSE, there was no single genotype of CA-MRSE
      disseminated among children even in the same institution or class.

PMID- 18832124
TI  - Assessment of specific antibodies to F protein in serum samples from Chinese
      hepatitis C patients treated with interferon plus ribavarin.
AB  - The hepatitis C virus (HCV) alternate reading frame protein or F protein of the
      HCV 1b genotype is a double-frameshift product of the HCV core protein. In order
      to assess the presence of antibodies specific for F protein and their clinical
      relevance in sera from HCV patients, we produced recombinant F protein and core
      protein of the HCV 1b genotype in Escherichia coli. An enzyme-linked
      immunosorbent assay was developed using purified recombinant HCV core, F protein,
      and a 99-residue synthetic F peptide (F99). The seroprevalences of anticore, anti
      F protein, and anti-F99 synthetic peptide were 95%, 68%, and 36%, respectively,
      in 168 HCV patients. The prevalence of anti-F antibodies did not correlate with
      viral load, genotype, or alanine aminotransferase level. Interferon combination
      therapy induced a decline in the level of anti-F antibodies in 55 responders (P <
      0.01). Thirteen responders (24%) lost their anti-F recombinant protein
      antibodies, and 17 (31%) lost their anti-F synthetic peptide antibodies, whereas
      no decrease was observed for the 17 nonresponders. These changes were significant
      between responders and nonresponders (P < 0.05). Meanwhile, no change was found
      in the anticore antibody titer of the 72 treated patients. The percentage of anti
      F-protein-negative patients (15/15 [100%]) who achieved a sustained virological
      response (SVR) was higher than that of the anti-F-positive patients (70%) (P <
      0.05). Based on these findings, HCV F protein elicits a specific antibody
      response other than the anticore protein response. Our data also suggest that the
      presence and level of anti-F antibody responses might be influenced by the
      treatment (interferon plus ribavirin) and associated with an SVR in Chinese
      hepatitis C patients.

PMID- 18832126
TI  - Rapid differentiation of methicillin-resistant Staphylococcus aureus and
      methicillin-susceptible Staphylococcus aureus from blood cultures by use of a
      direct cefoxitin disk diffusion test.
AB  - A total of 276 blood culture bottles with Staphylococcus aureus were tested by
      direct cefoxitin disk diffusion testing; 105 (38.1%) had zone sizes of </=17 mm
      (all 105 had methicillin-resistant S. aureus [MRSA]), 18 (6.5%) had zone sizes
      that measured 18 mm (17 had MRSA and 1 had methicillin-susceptible S. aureus
      [MSSA]), 8 (2.9%) had zone sizes that measured 19 mm (6 had MRSA and 2 had MSSA),
      8 (2.9%) had zone sizes that measured 20 mm (6 had MRSA and 2 had MSSA), and 137
      (49.6%) had zone sizes of >/=21 mm (all 137 had MSSA). Detection of MRSA/MSSA in
      blood cultures could be reported 10 to 24 h earlier for 88% of cultures with
      total accuracy.

PMID- 18832125
TI  - Genetic relatedness of Clostridium difficile isolates from various origins
      determined by triple-locus sequence analysis based on toxin regulatory genes
      tcdC, tcdR, and cdtR.
AB  - A triple-locus nucleotide sequence analysis based on toxin regulatory genes tcdC,
      tcdR and cdtR was initiated to assess the sequence variability of these genes
      among Clostridium difficile isolates and to study the genetic relatedness between
      isolates. A preliminary investigation of the variability of the tcdC gene was
      done with 57 clinical and veterinary isolates. Twenty-three isolates representing
      nine main clusters were selected for tcdC, tcdR, and cdtR analysis. The numbers
      of alleles found for tcdC, tcdR and cdtR were nine, six, and five, respectively.
      All strains possessed the cdtR gene except toxin A-negative toxin B-positive
      variants. All but one binary toxin CDT-positive isolate harbored a deletion (>1
      bp) in the tcdC gene. The combined analyses of the three genes allowed us to
      distinguish five lineages correlated with the different types of deletion in
      tcdC, i.e., 18 bp (associated or not with a deletion at position 117), 36 bp, 39
      bp, and 54 bp, and with the wild-type tcdC (no deletion). The tcdR and tcdC
      genes, though located within the same pathogenicity locus, were found to have
      evolved separately. Coevolution of the three genes was noted only with strains
      harboring a 39-bp or a 54-bp deletion in tcdC that formed two homogeneous,
      separate divergent clusters. Our study supported the existence of the known
      clones (PCR ribotype 027 isolates and toxin A-negative toxin B-positive C.
      difficile variants) and evidence for clonality of isolates with a 39-bp deletion
      (toxinotype V, PCR ribotype 078) that are frequently isolated worldwide from
      human infections and from food animals.

PMID- 18832127
TI  - Identification of Staphylococcus spp. by PCR-restriction fragment length
      polymorphism analysis of dnaJ gene.
AB  - A PCR-restriction fragment length polymorphism (RFLP) analysis method that
      analyzes a part of the dnaJ gene was designed for the rapid and accurate
      identification of Staphylococcus spp. XapI or Bsp143I digestion of the PCR
      generated products rendered distinctive RFLP patterns that allowed 41 reference
      species and subspecies to be identified with a high degree of specificity. The
      novel method was validated by the identification of 23 clinical staphylococcal
      strains, and the results were compared with those obtained by other genotypic
      identification methods. A 100% concordance of the results was shown. Therefore,
      PCR-RFLP analysis of the dnaJ gene is proposed as a reliable and reproducible
      method for the identification of Staphylococcus spp.

PMID- 18832128
TI  - Thymidine-dependent Staphylococcus aureus small-colony variants: human pathogens
      that are relevant not only in cases of cystic fibrosis lung disease.
AB  - We report the isolation of thymidine-dependent small-colony variants (TD-SCVs) of
      Staphylococcus aureus from unusual infection sites of patients with chronic soft
      tissue infection, tympanitis, bronchitis, peritonitis, and septicemia.
      Furthermore, we provide evidence that the essential growth factor for TD-SCVs,
      i.e., thymidine, and its metabolite dTMP are present in various human specimens.

PMID- 18832129
TI  - Comparison between the standardized clinical and laboratory standards institute
      M38-A2 method and a 2,3-Bis(2-Methoxy-4-Nitro-5-[(Sulphenylamino)Carbonyl]-2H
      tetrazolium hydroxide- based method for testing antifungal susceptibility of
      dermatophytes.
AB  - In this study, we determined the utility of a 2,3-bis(2-methoxy-4-nitro-5
      [(sulfenylamino)carbonyl]-2H-tetrazolium hydroxide (XTT)-based assay for
      determining antifungal susceptibilities of dermatophytes to terbinafine,
      ciclopirox, and voriconazole in comparison to the Clinical and Laboratory
      Standards Institute (CLSI) M38-A2 method. Forty-eight dermatophyte isolates,
      including Trichophyton rubrum (n = 15), Trichophyton mentagrophytes (n = 7),
      Trichophyton tonsurans (n = 11), and Epidermophyton floccosum (n = 13), and two
      quality control strains, were tested. In the XTT-based method, MICs were
      determined spectrophotometrically at 490 nm after addition of XTT and menadione.
      For the CLSI method, the MICs were determined visually. With T. rubrum, the XTT
      assay revealed MIC ranges of 0.004 to >64 mug/ml, 0.125 to 0.25 mug/ml, and 0.008
      to 0.025 mug/ml for terbinafine, ciclopirox, and voriconazole, respectively.
      Similar MIC ranges were obtained against T. rubrum by using the CLSI method.
      Additionally, when tested with T. mentagrophytes, T. tonsurans, and E. floccosum
      isolates, the XTT and CLSI methods resulted in comparable MIC ranges. Both
      methods revealed similar lowest drug concentrations that inhibited 90% of the
      isolates for the majority of tested drug-dermatophyte combinations. The levels of
      agreement within 1 dilution between both methods were as follows: 100% with
      terbinafine, 97.8% with ciclopirox, and 89.1% with voriconazole. However, the
      agreement within 2 dilutions between these two methods was 100% for all tested
      drugs. Our results revealed that the XTT assay can be a useful tool for
      antifungal susceptibility testing of dermatophytes.

PMID- 18832130
TI  - Genetic diversity of isoniazid-resistant Mycobacterium tuberculosis isolates
      collected in Poland and assessed by spoligotyping.
AB  - The genetic compositions of 71 isoniazid-resistant Mycobacterium tuberculosis
      strains from Poland were determined by spoligotyping. Nearly 80% of the isolates
      belonged to either the T or the Haarlem family. The genotypic diversity was
      largely due to variation within those families. The scarcity of imported
      genotypes suggested that the M. tuberculosis population studied has an endemic
      nature.

PMID- 18832131
TI  - Serotype distribution and penicillin resistance of Streptococcus pneumoniae
      isolates from middle ear fluids of pediatric patients with acute otitis media in
      Japan.
AB  - Out of 175 pneumococcal isolates from middle ear fluids, 26.3% were penicillin
      resistant S. pneumoniae (PRSP). Serotypes 19F and 23F occurred most frequently
      among PRSP strains. The 7-valent pneumococcal conjugate vaccine (PCV) showed
      better coverage of PRSP strains (87.0%). The 7-valent PCV may reduce the
      prevalence of PRSP in Japan.

PMID- 18832132
TI  - Isolation of a protozoan parasite genetically related to the insect
      trypanosomatid Herpetomonas samuelpessoai from a human immunodeficiency virus
      positive patient.
AB  - Severely immunocompromised human immunodeficiency virus (HIV) patients can
      develop various opportunistic infections due to bacteria, viruses, fungi, or
      protozoa. Here we report the first isolation of a flagellated protozoan
      genetically closely related to Herpetomonas samuelpessoai, which is usually a
      parasite of insects, from the blood of an HIV-infected patient.

PMID- 18832133
TI  - Analytical and clinical sensitivity of the 3M rapid detection influenza A+B
      assay.
AB  - The performance of the 3M rapid detection influenza A+B (3M flu) assay was
      compared to the performance of other immunochromatographic assays. The clinical
      and analytical performance of the 3M flu assay was superior to that of BinaxNOW
      and Directigen EZ assays and equivalent to that of the QuickVue assay. The 3M flu
      assay offers an objective output and direct linkage to laboratory information
      systems.

PMID- 18832134
TI  - Bone marrow-based homeostatic proliferation of mature T cells in nonhuman
      primates: implications for AIDS pathogenesis.
AB  - Bone marrow (BM) is the key hematopoietic organ in mammals and is involved in the
      homeostatic proliferation of memory CD8(+) T cells. Here we expanded on our
      previous observation that BM is a preferential site for T-cell proliferation in
      simian immunodeficiency virus (SIV)-infected sooty mangabeys (SMs) that do not
      progress to AIDS despite high viremia. We found high levels of mature T-cell
      proliferation, involving both naive and memory cells, in healthy SMs and rhesus
      macaques (RMs). In addition, we observed in both species that lineage-specific,
      BM-based T-cell proliferation follows antibody-mediated in vivo CD4(+) or CD8(+)
      T-cell depletion, thus indicating a role for the BM in maintaining T-cell
      homeostasis under depleting circumstances. We also observed that, in SIV-infected
      SMs, but not RMs, the level of proliferation of BM-based CD4(+) T cells is higher
      than that of circulating CD4(+) T cells. Interestingly, limited BM-based CD4(+) T
      cell proliferation was found in SIV-infected SMs with low CD4(+) T-cell counts,
      suggesting a regenerative failure in these animals. Collectively, these results
      indicate that BM is involved in maintaining T-cell homeostasis in primates and
      suggest a role for BM-based CD4(+) T-cell proliferation in determining the benign
      nature of natural SIV infection of SMs.

PMID- 18832135
TI  - Oncogenomic analysis of mycosis fungoides reveals major differences with Sezary
      syndrome.
AB  - Mycosis fungoides (MF), the most common cutaneous T-cell lymphoma, is a
      malignancy of mature, skin-homing T cells. Sezary syndrome (Sz) is often
      considered to represent a leukemic phase of MF. In this study, the pattern of
      numerical chromosomal alterations in MF tumor samples was defined using array
      based comparative genomic hybridization (CGH); simultaneously, gene expression
      was analyzed using microarrays. Highly recurrent chromosomal alterations in MF
      include gain of 7q36, 7q21-7q22 and loss of 5q13 and 9p21. The pattern
      characteristic of MF differs markedly from chromosomal alterations observed in
      Sz. Integration of data from array-based CGH and gene-expression analysis yielded
      several candidate genes with potential relevance in the pathogenesis of MF. We
      confirmed that the FASTK and SKAP1 genes, residing in loci with recurrent gain,
      demonstrated increased expression. The RB1 and DLEU1 tumor suppressor genes
      showed diminished expression associated with loss. In addition, it was found that
      the presence of chromosomal alterations on 9p21, 8q24, and 1q21-1q22 was
      associated with poor prognosis in patients with MF. This study provides novel
      insight into genetic alterations underlying MF. Furthermore, our analysis
      uncovered genomic differences between MF and Sz, which suggest that the molecular
      pathogenesis and therefore therapeutic requirements of these cutaneous T-cell
      lymphomas may be distinct.

PMID- 18832136
TI  - Enhancement of DNA tumor vaccine efficacy by gene gun-mediated codelivery of
      threshold amounts of plasmid-encoded helper antigen.
AB  - Nucleic acid-based vaccines are effective in infectious disease models but have
      yielded disappointing results in tumor models when tumor-associated self-antigens
      are used. Incorporation of helper epitopes from foreign antigens into tumor
      vaccines might enhance the immunogenicity of DNA vaccines without increasing
      toxicity. However, generation of fusion constructs encoding both tumor and helper
      antigens may be difficult, and resulting proteins have unpredictable physical and
      immunologic properties. Furthermore, simultaneous production of equal amounts of
      highly immunogenic helper and weakly immunogenic tumor antigens in situ could
      favor development of responses against the helper antigen rather than the antigen
      of interest. We assessed the ability of 2 helper antigens (beta-galactosidase or
      fragment C of tetanus toxin) encoded by one plasmid to augment responses to a
      self-antigen (lymphoma-associated T-cell receptor) encoded by a separate plasmid
      after codelivery into skin by gene gun. This approach allowed adjustment of the
      relative ratios of helper and tumor antigen plasmids to optimize helper effects.
      Incorporation of threshold (minimally immunogenic) amounts of helper antigen
      plasmid into a DNA vaccine regimen dramatically increased T cell-dependent
      protective immunity initiated by plasmid-encoded tumor-associated T-cell receptor
      antigen. This simple strategy can easily be incorporated into future vaccine
      trials in experimental animals and possibly in humans.

PMID- 18832137
TI  - Not all drinks are created equal: implications for alcohol assessment in India.
AB  - AIMS: There is sparse literature on drink alcohol content in developing
      countries. This study documented detailed information on drink sizes and ethanol
      content of alcoholic beverages consumed in three different parts of India.
      METHODS: Data primarily from formative phases of studies on alcohol use patterns
      in the states of Delhi, Rajasthan and Goa are reported. Participant observation
      and semi-structured interviews with key informants and drinking respondents were
      used to assess different beverage types and to empirically measure actual drink
      sizes as poured. Investigation of ethanol content included the use of biochemical
      analyses, the alcoholmeter and the Analox Analyser AM3. Respondents interviewed
      in the post-formative phase in one study were also asked to define the volume of
      their drinks by indicating pour levels in select drinking vessels. RESULTS: A
      wide range of alcoholic drinks were documented that varied in ethanol
      concentration across and within sites. Drink sizes, particularly for high
      strength beverages, varied both by study site and respondent, with pours of
      distilled spirits on average being larger than standard measures. CONCLUSION:
      Estimates of both mean volume of alcohol consumption and heavy drinking amounts
      are influenced by variability in alcohol concentration and respondent-defined
      pour sizes. The variation in drink alcohol content found across Indian states
      indicates that prior to conducting quantitative surveys, preliminary work on
      sources of drink alcohol content variation should be undertaken to tailor
      measurement tools to specific beverages and drinking practices observed.
      Recommendations for alcohol research in developing countries are provided.

PMID- 18832138
TI  - The alcoholic phenotypes among different multidimensional typologies:
      similarities and their classification procedures.
AB  - AIM: This detailed cross-sectional analysis, obtained from a sample of alcohol
      dependent patients, attempts to compare multiple methods that have been created
      to classify or subtype alcoholics. METHODS: The sample comprised 318 alcohol
      dependent patients recruited from the alcoholism unit (NETER) of the Psychiatric
      Service of Santa Maria University Hospital in Lisbon (Portugal). All subjects
      were evaluated during the outpatient therapeutical programme for operationalized
      criteria, reported by each alcoholism typology. RESULTS: Regarding concordance
      agreement (kappa values) for the three type I/II classifications, von Knorring
      versus Sullivan yielded the higher rate of agreement, followed by von Knorring
      versus Gilligan and Gilligan versus Sullivan criteria. Chi-square comparisons
      showed a significant overlap between Babor type A and Cloninger type I of von
      Knorring and Sullivan. Over-two-type classifications showed the following
      significant positive relations: Lesch type I versus NETER heredopathic subtype;
      Lesch type II versus NETER anxiopathic subtype and Babor type A; Lesch type III
      versus NETER tymopathic subtype; Lesch type IV versus Cloninger type II of von
      Knorring and Sullivan criteria; and NETER adictopathic subtype versus Cloninger
      type II of von Knorring, Sullivan and Gilligan criteria. CONCLUSIONS: There is a
      significant overlap across many of the multivariate alcoholic subtypes purposed,
      in which much of the concordance is a function of common characteristics in
      subtype operationalization. Commonalities among these different subtyping
      classification systems offers the possibility of identifying important dimensions
      that better differentiate individuals among problem drinker's populations.

PMID- 18832139
TI  - Making the lame walk?: transplantation for POEMS.

PMID- 18832140
TI  - Neurologic improvement after peripheral blood stem cell transplantation in POEMS
      syndrome.
AB  - BACKGROUND: Polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin
      changes (POEMS) syndrome is a rare multisystem disorder associated with plasma
      cell dyscrasia. There is increasing evidence that high-dose chemotherapy with
      autologous peripheral blood stem cell transplantation (Auto-PBSCT) is an
      efficacious treatment. OBJECTIVE: To elucidate the extent and time course of
      neurologic improvement after Auto-PBSCT in patients with POEMS syndrome. METHODS:
      Clinical and electrophysiologic findings in nine patients were reviewed. The
      median follow-up period was 20 months (range, 8 to 49 months). Serum levels of
      vascular endothelial growth factor (VEGF) were measured by ELISA. RESULTS: Serum
      VEGF levels rapidly decreased a month after Auto-PBSCT. Within 3 months,
      neurologic improvement began, and all the patients showed substantial neurologic
      recovery during the next 3 months. Particularly, three initially chairbound
      patients regained ability to walk at 6 months. Nerve conduction studies showed
      significant increases in conduction velocities and amplitudes within 6 months of
      treatment. At the end of follow-up periods, neuropathy was still improving, and
      no patients had recurrence of symptoms. CONCLUSION: Autologous peripheral blood
      stem cell transplantation results in obvious neurologic improvement within 6
      months, presumably by extensive axonal regeneration and remyelination. This
      therapy could be considered as a first line treatment for patients with
      polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes
      syndrome with younger onset even if they are tetraplegic.

PMID- 18832141
TI  - Mutations in the HSP27 (HSPB1) gene cause dominant, recessive, and sporadic
      distal HMN/CMT type 2.
AB  - BACKGROUND: Charcot-Marie-Tooth disease (CMT) is the most common inherited
      neuromuscular disorder and is characterized by significant clinical and genetic
      heterogeneity. Recently, mutations in both the small heat shock protein 27 (HSP27
      or HSPB1) and 22 (HSP22 or HSPB8) genes have been reported to cause autosomal
      dominant CMT with minimal sensory involvement (CMT 2F/CMT2L) and autosomal
      dominant distal hereditary motor neuropathy type II (dHMN II). METHODS: We
      analyzed the HSPB1 and HSPB8 genes in a large clinically well-characterized
      series of dHMN and CMT type 2 (CMT2) cases and families using linkage analysis
      and direct sequencing of these genes. RESULTS: We identified a novel homozygous
      mutation in the alpha-crystallin domain of HSPB1 segregating in an autosomal
      recessive fashion in a family with distal HMN/CMT2. A further four heterozygous
      HSPB1 mutations were identified in four autosomal dominant families dHMN/CMT2,
      and two sporadic cases were identified with probable de novo mutations. In the
      autosomal dominant and autosomal recessive families, there were no clinical
      sensory findings, but reduced sural nerve action potential amplitudes were found
      in some affected individuals, indicating that long sensory axons are mildly
      affected in this predominantly motor disorder. CONCLUSIONS: This extends the
      clinical and electrophysiologic spectrum of HSPB1 mutations and identifies four
      unreported dominant HSPB1 mutations and the first family where the HSPB1 mutation
      acts in a recessive way to cause distal HMN.

PMID- 18832142
TI  - Poxvirus transcriptome analysis.

PMID- 18832143
TI  - Bioinformatics identification of MurJ (MviN) as the peptidoglycan lipid II
      flippase in Escherichia coli.
AB  - Peptidoglycan is a cell-wall glycopeptide polymer that protects bacteria from
      osmotic lysis. Whereas in gram-positive bacteria it also serves as scaffold for
      many virulence factors, in gram-negative bacteria, peptidoglycan is an anchor for
      the outer membrane. For years, we have known the enzymes required for the
      biosynthesis of peptidoglycan; what was missing was the flippase that
      translocates the lipid-anchored precursors across the cytoplasmic membrane before
      their polymerization into mature peptidoglycan. Using a reductionist
      bioinformatics approach, I have identified the essential inner-membrane protein
      MviN (renamed MurJ) as a likely candidate for the peptidoglycan flippase in
      Escherichia coli. Here, I present genetic and biochemical data that confirm the
      requirement of MurJ for peptidoglycan biosynthesis and that are in agreement with
      a role of MurJ as a flippase. Because of its essential nature, MurJ could serve
      as a target in the continuing search for antimicrobial compounds.

PMID- 18832144
TI  - The bacteriophage lambda Q antiterminator protein contacts the beta-flap domain
      of RNA polymerase.
AB  - The multisubunit RNA polymerase (RNAP) in bacteria consists of a catalytically
      active core enzyme (alpha(2)beta beta'omega) complexed with a sigma factor that
      is required for promoter-specific transcription initiation. During early
      elongation the stability of interactions between sigma and core decreases, in
      part because of the nascent RNA-mediated destabilization of an interaction
      between region 4 of sigma and the flap domain of the beta-subunit (beta-flap).
      The nascent RNA-mediated destabilization of the sigma region 4/beta-flap
      interaction is required for the bacteriophage lambda Q antiterminator protein
      (lambdaQ) to engage the RNAP holoenzyme. Here, we provide an explanation for this
      requirement by showing that lambdaQ establishes direct contact with the beta-flap
      during the engagement process, thus competing with sigma(70) region 4 for access
      to the beta-flap. We also show that lambdaQ's affinity for the beta-flap is
      calibrated to ensure that lambdaQ activity is restricted to the lambda late
      promoter P(R'). Specifically, we find that strengthening the lambdaQ/beta-flap
      interaction allows lambdaQ to bypass the requirement for specific cis-acting
      sequence elements, a lambdaQ-DNA binding site and a RNAP pause-inducing element,
      that normally ensure lambdaQ is recruited exclusively to transcription complexes
      associated with P(R'). Our findings demonstrate that the beta-flap can serve as a
      direct target for regulators of elongation.

PMID- 18832145
TI  - Dissecting the role of cadherin-catenin proteins in mammalian epidermis.

PMID- 18832146
TI  - Deletion of TrkB in adult progenitors alters newborn neuron integration into
      hippocampal circuits and increases anxiety-like behavior.
AB  - New neurons in the adult dentate gyrus are widely held to incorporate into
      hippocampal circuitry via a stereotypical sequence of morphological and
      physiological transitions, yet the molecular control over this process remains
      unclear. We studied the role of brain-derived neurotrophic factor (BDNF)/TrkB
      signaling in adult neurogenesis by deleting the full-length TrkB via Cre
      expression within adult progenitors in TrkB(lox/lox) mice. By 4 weeks after
      deletion, the growth of dendrites and spines is reduced in adult-born neurons
      demonstrating that TrkB is required to create the basic organization of synaptic
      connections. Later, when new neurons normally display facilitated synaptic
      plasticity and become preferentially recruited into functional networks, lack of
      TrkB results in impaired neurogenesis-dependent long-term potentiation and cell
      survival becomes compromised. Because of the specific lack of TrkB signaling in
      recently generated neurons a remarkably increased anxiety-like behavior was
      observed in mice carrying the mutation, emphasizing the contribution of adult
      neurogenesis in regulating mood-related behavior.

PMID- 18832147
TI  - Rediscovery of an "extinct" Galapagos tortoise.

PMID- 18832148
TI  - Differential dependence of phasic transmitter release on synaptotagmin 1 at
      GABAergic and glutamatergic hippocampal synapses.
AB  - Previous studies revealed that synaptotagmin 1 is the major Ca(2+) sensor for
      fast synchronous transmitter release at excitatory synapses. However, the
      molecular identity of the Ca(2+) sensor at hippocampal inhibitory synapses has
      not been determined. To address the functional role of synaptotagmin 1 at
      identified inhibitory terminals, we made paired recordings from synaptically
      connected basket cells (BCs) and granule cells (GCs) in the dentate gyrus in
      organotypic slice cultures from wild-type and synaptotagmin 1-deficient mice. As
      expected, genetic elimination of synaptotagmin 1 abolished synchronous
      transmitter release at excitatory GC-BC synapses. However, synchronous release at
      inhibitory BC-GC synapses was maintained. Quantitative analysis revealed that
      elimination of synaptotagmin 1 reduced release probability and depression but
      maintained the synchrony of transmitter release at BC-GC synapses. Elimination of
      synaptotagmin 1 also increased the frequency of both miniature excitatory
      postsynaptic currents (measured in BCs) and miniature inhibitory postsynaptic
      currents (recorded in GCs), consistent with a clamping function of synaptotagmin
      1 at both excitatory and inhibitory terminals. Single-cell reverse-transcription
      quantitative PCR analysis revealed that single BCs coexpressed multiple
      synaptotagmin isoforms, including synaptotagmin 1-5, 7, and 11-13. Our results
      indicate that, in contrast to excitatory synapses, synaptotagmin 1 is not
      absolutely required for synchronous release at inhibitory BC-GC synapses. Thus,
      alternative fast Ca(2+) sensors contribute to synchronous release of the
      inhibitory transmitter GABA in cortical circuits.

PMID- 18832149
TI  - Circumspect descent prevails in solving random constraint satisfaction problems.
AB  - We study the performance of stochastic local search algorithms for random
      instances of the K-satisfiability (K-SAT) problem. We present a stochastic local
      search algorithm, ChainSAT, which moves in the energy landscape of a problem
      instance by never going upwards in energy. ChainSAT is a focused algorithm in the
      sense that it focuses on variables occurring in unsatisfied clauses. We show by
      extensive numerical investigations that ChainSAT and other focused algorithms
      solve large K-SAT instances almost surely in linear time, up to high clause-to
      variable ratios alpha; for example, for K = 4 we observe linear-time performance
      well beyond the recently postulated clustering and condensation transitions in
      the solution space. The performance of ChainSAT is a surprise given that by
      design the algorithm gets trapped into the first local energy minimum it
      encounters, yet no such minima are encountered. We also study the geometry of the
      solution space as accessed by stochastic local search algorithms.

PMID- 18832150
TI  - The remarkable influence of M2delta to thienyl pi conjugation in oligothiophenes
      incorporating MM quadruple bonds.
AB  - Oligothiophenes incorporating MM quadruple bonds have been prepared from the
      reactions between Mo(2)(TiPB)(4) (TiPB = 2,4,6-triisopropyl benzoate) and 3',4'
      dihexyl-2,2'-:5',2''-terthiophene-5,5''-dicarboxylic acid. The oligomers of
      empirical formula Mo(2)(TiPB)(2)(O(2)C(Th)-C(4)(n-hexyl)(2)S-(Th)CO(2)) are
      soluble in THF and form thin films with spin-coating (Th = thiophene). The
      reactions between Mo(2)(TiPB)(4) and 2-thienylcarboxylic acid (Th-H), 2,2'
      bithiophene-5-carboxylic acid (BTh-H), and (2,2':5',2''-terthiophene)-5
      carboxylic acid (TTh-H) yield compounds of formula trans-Mo(2)(TiPB)(2)L(2),
      where L = Th, BTh, and TTh (the corresponding thienylcarboxylate), and these
      compounds are considered as models for the aforementioned oligomers. In all
      cases, the thienyl groups are substituted or coupled at the 2,5 positions. Based
      on the x-ray analysis, the molecular structure of trans-Mo(2)(TiPB)(2)(BTh)(2)
      reveals an extended Lpi-M(2)delta-Lpi conjugation. Calculations of the electronic
      structures on model compounds, in which the TiPB are substituted by formate
      ligands, reveal that the HOMO is mainly attributed to the M(2)delta orbital,
      which is stabilized by back-bonding to one of the thienylcarboxylate pi*
      combinations, and the LUMO is an in-phase combination of the thienylcarboxylate
      pi* orbitals. The compounds and the oligomers are intensely colored due to
      M(2)delta-thienyl carboxylate pi* charge transfer transitions that fall in the
      visible region of the spectrum. For the molybdenum complexes and their oligomers,
      the photophysical properties have been studied by steady-state absorption
      spectroscopy and emission spectroscopy, together with time-resolved emission and
      transient absorption for the determination of relaxation dynamics. Remarkably,
      THF solutions the molybdenum complexes show room-temperature dual emission,
      fluorescence and phosphorescence, originating mainly from (1)MLCT and
      (3)MM(deltadelta*) states, respectively. With increasing number of thienyl rings
      from 1 to 3, the observed lifetimes of the (1)MLCT state increase from 4 to 12
      ps, while the phosphorescence lifetimes are approximately 80 micros. The
      oligomers show similar photophysical properties as the corresponding monomers in
      THF but have notably longer-lived triplet states, approximately 200 micros in
      thin films. These results, when compared with metallated oligothiophenes of the
      later transition elements, reveal that M(2)delta-thienyl pi conjugation leads to
      a very small energy gap between the (1)MLCT and (3)MLCT states of <0.6 eV.

PMID- 18832151
TI  - Evolution of vertebrate opioid receptors.
AB  - The opioid peptides and receptors have prominent roles in pain transmission and
      reward mechanisms in mammals. The evolution of the opioid receptors has so far
      been little studied, with only a few reports on species other than tetrapods. We
      have investigated species representing a broader range of vertebrates and found
      that the four opioid receptor types (delta, kappa, mu, and NOP) are present in
      most of the species. The gene relationships were deduced by using both
      phylogenetic analyses and chromosomal location relative to 20 neighboring gene
      families in databases of assembled genomes. The combined results show that the
      vertebrate opioid receptor gene family arose by quadruplication of a large
      chromosomal block containing at least 14 other gene families. The quadruplication
      seems to coincide with, and, therefore, probably resulted from, the two proposed
      genome duplications in early vertebrate evolution. We conclude that the quartet
      of opioid receptors was already present at the origin of jawed vertebrates
      approximately 450 million years ago. A few additional opioid receptor gene
      duplications have occurred in bony fishes. Interestingly, the ancestral receptor
      gene duplications coincide with the origin of the four opioid peptide precursor
      genes. Thus, the complete vertebrate opioid system was already established in the
      first jawed vertebrates.

PMID- 18832152
TI  - Gene expression changes in the course of normal brain aging are sexually
      dimorphic.
AB  - Gene expression profiles were assessed in the hippocampus, entorhinal cortex,
      superior-frontal gyrus, and postcentral gyrus across the lifespan of 55
      cognitively intact individuals aged 20-99 years. Perspectives on global gene
      changes that are associated with brain aging emerged, revealing two overarching
      concepts. First, different regions of the forebrain exhibited substantially
      different gene profile changes with age. For example, comparing equally powered
      groups, 5,029 probe sets were significantly altered with age in the superior
      frontal gyrus, compared with 1,110 in the entorhinal cortex. Prominent change
      occurred in the sixth to seventh decades across cortical regions, suggesting that
      this period is a critical transition point in brain aging, particularly in males.
      Second, clear gender differences in brain aging were evident, suggesting that the
      brain undergoes sexually dimorphic changes in gene expression not only in
      development but also in later life. Globally across all brain regions, males
      showed more gene change than females. Further, Gene Ontology analysis revealed
      that different categories of genes were predominantly affected in males vs.
      females. Notably, the male brain was characterized by global decreased catabolic
      and anabolic capacity with aging, with down-regulated genes heavily enriched in
      energy production and protein synthesis/transport categories. Increased immune
      activation was a prominent feature of aging in both sexes, with proportionally
      greater activation in the female brain. These data open opportunities to explore
      age-dependent changes in gene expression that set the balance between
      neurodegeneration and compensatory mechanisms in the brain and suggest that this
      balance is set differently in males and females, an intriguing idea.

PMID- 18832153
TI  - Cohesin subunit SMC1 associates with mitotic microtubules at the spindle pole.
AB  - Accurate mitotic chromosome segregation depends on the formation of a microtubule
      based bipolar spindle apparatus. We report that the cohesin subunit structural
      maintenance of chromosomes subunit 1 (SMC1) is recruited to microtubule-bound RNA
      export factor 1 (Rae1) at the mitotic spindle pole. We locate the Rae1-binding
      site to a 21-residue-long region, SMC1(947-967) and provide several lines of
      evidence that phosphorylation of Ser(957) and Ser(966) of SMC1 stimulates binding
      to Rae1. Imbalances in these assembly pathways caused formation of multipolar
      spindles. Our data suggest that cohesin's known bundling function for chromatids
      in mitotic and interphase cells extends to microtubules at the spindle pole.

PMID- 18832154
TI  - Neuregulin-1 regulates LTP at CA1 hippocampal synapses through activation of
      dopamine D4 receptors.
AB  - Neuregulin-1 (NRG-1) is genetically linked with schizophrenia, a
      neurodevelopmental cognitive disorder characterized by imbalances in
      glutamatergic and dopaminergic function. NRG-1 regulates numerous
      neurodevelopmental processes and, in the adult, suppresses or reverses long-term
      potentiation (LTP) at hippocampal glutamatergic synapses. Here we show that NRG-1
      stimulates dopamine release in the hippocampus and reverses early-phase LTP via
      activation of D4 dopamine receptors (D4R). NRG-1 fails to depotentiate LTP in
      hippocampal slices treated with the antipsychotic clozapine and other more
      selective D4R antagonists. Moreover, LTP is not depotentiated in D4R null mice by
      either NRG-1 or theta-pulse stimuli. Conversely, direct D4R activation mimics NRG
      1 and reduces AMPA receptor currents and surface expression. These findings
      demonstrate that NRG-1 mediates its unique role in counteracting LTP via dopamine
      signaling and opens future directions to study new aspects of NRG function. The
      novel functional link between NRG-1, dopamine, and glutamate has important
      implications for understanding how imbalances in Neuregulin-ErbB signaling can
      impinge on dopaminergic and glutamatergic function, neurotransmitter pathways
      associated with schizophrenia.

PMID- 18832155
TI  - Light-induced chromophore activity and signal transduction in phytochromes
      observed by 13C and 15N magic-angle spinning NMR.
AB  - Both thermally stable states of phytochrome, Pr and Pfr, have been studied by
      (13)C and (15)N cross-polarization (CP) magic-angle spinning (MAS) NMR using
      cyanobacterial (Cph1) and plant (phyA) phytochrome sensory modules containing
      uniformly (13)C- and (15)N-labeled bilin chromophores. Two-dimensional homo- and
      heteronuclear experiments allowed most of the (13)C chemical shifts to be
      assigned in both states. Chemical shift differences reflect changes of the
      electronic structure of the cofactor at the atomic level as well as its
      interactions with the chromophore-binding pocket. The chromophore in
      cyanobacterial and plant phytochromes shows very similar features in the
      respective Pr and Pfr states. The data are interpreted in terms of a strengthened
      hydrogen bond at the ring D carbonyl. The red shift in the Pfr state is explained
      by the increasing length of the conjugation network beyond ring C including the
      entire ring D. Enhanced conjugation within the pi-system stabilizes the more
      tensed chromophore in the Pfr state. Concomitant changes at the ring C propionate
      carboxylate and the ring D carbonyl are explained by a loss of hydrogen bonding
      to Cph1-His-290 and transmittance of conformational changes to the ring C
      propionate via a water network. These and other conformational changes may lead
      to modified surface interactions, e.g., along the tongue region contacting the
      bilin chromophore.

PMID- 18832156
TI  - Generation and regulation of human CD4+ IL-17-producing T cells in ovarian
      cancer.
AB  - Despite the important role of Th17 cells in the pathogenesis of many autoimmune
      diseases, their prevalence and the mechanisms by which they are generated and
      regulated in cancer remain unclear. Here, we report the presence of a high
      percentage of CD4(+) Th17 cells at sites of ovarian cancer, compared with a low
      percentage of Th17 cells in peripheral blood mononuclear cells from healthy
      donors and cancer patients. Analysis of cytokine production profiles revealed
      that ovarian tumor cells, tumor-derived fibroblasts, and antigen-presenting cells
      (APCs) secreted several key cytokines including IL-1beta, IL-6, TNF-alpha and TGF
      beta, which formed a cytokine milieu that regulated and expanded human IL-17
      producing T-helper (Th17) cells. We further show that IL-1beta was critically
      required for the differentiation and expansion of human Th17 cells, whereas IL-6
      and IL-23 may also play a role in the expansion of memory Th17 cells, even though
      IL-23 levels are low or undetectable in ovarian cancer. Further experiments
      demonstrated that coculture of naive or memory CD4(+) T cells with tumor cells,
      APCs, or both could generate high percentages of Th17 cells. Treatment with anti
      IL-1 alone or a combination of anti-IL-1 and anti-IL-6 reduced the ability of
      tumor cells to expand memory Th17 cells. Thus, we have identified a set of key
      cytokines secreted by ovarian tumor cells and tumor-associated APCs that favor
      the generation and expansion of human Th17 cells. These findings should
      accelerate efforts to define the function of this important subset of CD4(+) T
      cells in the human immune response to cancer.

PMID- 18832157
TI  - Sustained retrotransposition is mediated by nucleotide deletions and interelement
      recombinations.
AB  - The term "C-value paradox" was coined by C. A. Thomas, Jr. in 1971 [Thomas CA
      (1971) Ann Rev Genetics 5:237-256] to describe the initially puzzling lack of
      correlation between an organism's genome size and its morphological complexity.
      Polyploidy and the expansion of repetitive DNA, primarily transposable elements,
      are two mechanisms that have since been found to account for this differential.
      While the inactivation of retrotransposons by methylation and their removal from
      the genome by illegitimate recombination have been well documented, the cause of
      the apparently periodic bursts of retrotranposon expansion is as yet unknown. We
      show that the expansion of the CRM1 retrotransposon subfamily in the ancient
      allotetraploid crop plant corn is linked to the repeated formation of novel
      recombinant elements derived from two parental retrotransposon genotypes, which
      may have been brought together during the hybridization of two sympatric species
      that make up the present day corn genome, thus revealing a unique mechanism
      linking polyploidy and retrotransposition.

PMID- 18832158
TI  - Structure of the human voltage-dependent anion channel.
AB  - The voltage-dependent anion channel (VDAC), also known as mitochondrial porin, is
      the most abundant protein in the mitochondrial outer membrane (MOM). VDAC is the
      channel known to guide the metabolic flux across the MOM and plays a key role in
      mitochondrially induced apoptosis. Here, we present the 3D structure of human
      VDAC1, which was solved conjointly by NMR spectroscopy and x-ray crystallography.
      Human VDAC1 (hVDAC1) adopts a beta-barrel architecture composed of 19 beta
      strands with an alpha-helix located horizontally midway within the pore.
      Bioinformatic analysis indicates that this channel architecture is common to all
      VDAC proteins and is adopted by the general import pore TOM40 of mammals, which
      is also located in the MOM.

PMID- 18832159
TI  - Jellyfish vision starts with cAMP signaling mediated by opsin-G(s) cascade.
AB  - Light sensing starts with phototransduction in photoreceptor cells. The
      phototransduction cascade has diverged in different species, such as those
      mediated by transducin in vertebrate rods and cones, by G(q)-type G protein in
      insect and molluscan rhabdomeric-type visual cells and vertebrate photosensitive
      retinal ganglion cells, and by G(o)-type G protein in scallop ciliary-type visual
      cells. Here, we investigated the phototransduction cascade of a prebilaterian box
      jellyfish, the most basal animal having eyes containing lens and ciliary-type
      visual cells similar to vertebrate eyes, to examine the similarity at the
      molecular level and to obtain an implication of the origin of the vertebrate
      phototransduction cascade. We showed that the opsin-based pigment functions as a
      green-sensitive visual pigment and triggers the G(s)-type G protein-mediated
      phototransduction cascade in the ciliary-type visual cells of the box jellyfish
      lens eyes. We also demonstrated the light-dependent cAMP increase in the
      jellyfish visual cells and HEK293S cells expressing the jellyfish opsin. The
      first identified prebilaterian cascade was distinct from known phototransduction
      cascades but exhibited significant partial similarity with those in vertebrate
      and molluscan ciliary-type visual cells, because all involved cyclic nucleotide
      signaling. These similarities imply a monophyletic origin of ciliary
      phototransduction cascades distributed from prebilaterian to vertebrate.

PMID- 18832160
TI  - Mg2+-sensing mechanism of Mg2+ transporter MgtE probed by molecular dynamics
      study.
AB  - Proper regulation of the intracellular ion concentration is essential to maintain
      life and is achieved by ion transporters that transport their substrates across
      the membrane in a strictly regulated manner. MgtE is a Mg(2+) transporter that
      may function in the homeostasis of the intracellular Mg(2+) concentration. A
      recent crystallographic study revealed that its cytosolic domain undergoes a
      Mg(2+)-dependent structural change, which is proposed to gate the ion-conducting
      pore passing through the transmembrane domain. However, the dynamics of Mg(2+)
      sensing, i.e., how MgtE responds to the change in the intracellular Mg(2+)
      concentration, remained elusive. Here we performed molecular dynamics simulations
      of the MgtE cytosolic domain. The simulations successfully reproduced the
      structural changes of the cytosolic domain upon binding or releasing Mg(2+), as
      well as the ion selectivity. These results suggested the roles of the N and CBS
      domains in the cytosolic domain and their respective Mg(2+) binding sites.
      Combined with the current crystal structures, we propose an atomically detailed
      model of Mg(2+) sensing by MgtE.

PMID- 18832161
TI  - From particles to spins: Eulerian formulation of supercooled liquids and glasses.
AB  - The dynamics of supercooled liquid and glassy systems are usually studied within
      the Lagrangian representation, in which the positions and velocities of
      distinguishable interacting particles are followed. Within this representation,
      however, it is difficult to define measures of spatial heterogeneities in the
      dynamics, as particles move in and out of any one given region within long enough
      times. It is also nontransparent how to make connections between the structural
      glass and the spin glass problems within the Lagrangian formulation. We propose
      an Eulerian formulation of supercooled liquids and glasses that allows for a
      simple connection between particle and spin systems, and that permits the study
      of dynamical heterogeneities within a fixed frame of reference similar to the one
      used for spin glasses. We apply this framework to the study of the dynamics of
      colloidal particle suspensions for packing fractions corresponding to the
      supercooled and glassy regimes, which are probed via confocal microscopy.

PMID- 18832162
TI  - Variable stoichiometry of the TatA component of the twin-arginine protein
      transport system observed by in vivo single-molecule imaging.
AB  - The twin-arginine translocation (Tat) system transports folded proteins across
      the bacterial cytoplasmic membrane and the thylakoid membrane of plant
      chloroplasts. The essential components of the Tat pathway are the membrane
      proteins TatA, TatB, and TatC. TatA is thought to form the protein translocating
      element of the Tat system. Current models for Tat transport make predictions
      about the oligomeric state of TatA and whether, and how, this state changes
      during the transport cycle. We determined the oligomeric state of TatA directly
      at native levels of expression in living cells by photophysical analysis of
      individual yellow fluorescent protein-labeled TatA complexes. TatA forms
      complexes exhibiting a broad range of stoichiometries with an average of
      approximately 25 TatA subunits per complex. Fourier analysis of the stoichiometry
      distribution suggests the complexes are assembled from tetramer units. Modeling
      the diffusion behavior of the complexes suggests that TatA protomers associate as
      a ring and not a bundle. Each cell contains approximately 15 mobile TatA
      complexes and a pool of approximately 100 TatA molecules in a more disperse state
      in the membrane. Dissipation of the protonmotive force that drives Tat transport
      has no affect on TatA complex stoichiometry. TatA complexes do not form in cells
      lacking TatBC, suggesting that TatBC controls the oligomeric state of TatA. Our
      data support the TatA polymerization model for the mechanism of Tat transport.

PMID- 18832163
TI  - Association of the Agrobacterium T-DNA-protein complex with plant nucleosomes.
AB  - Agrobacterium represents the only natural example of transkingdom transfer of
      genetic information, from bacteria to plants. Before the bacterial transferred
      DNA (T-DNA) can integrate into the plant genome, it should be targeted to and
      bind the host chromatin. However, the T-DNA association with the host chromatin
      has not been demonstrated. Here, we study T-DNA binding to plant nucleosomes in
      vitro and show that it is mediated by bacterial and host proteins associated with
      the T-DNA. The main factor that determines nucleosomal binding of the T-DNA is
      the cellular VirE2-interacting protein 1 (VIP1), which functions as a molecular
      link between the T-DNA-associated bacterial virulence protein VirE2 and core
      histones. The presence of both VIP1 and VirE2 is required for association of the
      T-DNA with mononucleosomes in which the DNA molecule exists as a tripartite
      complex DNA-VirE2-VIP1. Furthermore, this nucleosome-associated ternary complex
      can bind another bacterial virulence factor, VirF, which is an F-box protein
      known to target both VirE2 and VIP1 for proteasomal degradation and uncoat the T
      DNA.

PMID- 18832164
TI  - NPC1/NPC2 function as a tag team duo to mobilize cholesterol.

PMID- 18832165
TI  - The control of Ca2+ influx and NFATc3 signaling in arterial smooth muscle during
      hypertension.
AB  - Many excitable cells express L-type Ca(2+) channels (LTCCs), which participate in
      physiological and pathophysiological processes ranging from memory, secretion,
      and contraction to epilepsy, heart failure, and hypertension. Clusters of LTCCs
      can operate in a PKCalpha-dependent, high open probability mode that generates
      sites of sustained Ca(2+) influx called "persistent Ca(2+) sparklets." Although
      increased LTCC activity is necessary for the development of vascular dysfunction
      during hypertension, the mechanisms leading to increased LTCC function are
      unclear. Here, we tested the hypothesis that increased PKCalpha and persistent
      Ca(2+) sparklet activity contributes to arterial dysfunction during hypertension.
      We found that PKCalpha and persistent Ca(2+) sparklet activity is indeed
      increased in arterial myocytes during hypertension. Furthermore, in human
      arterial myocytes, PKCalpha-dependent persistent Ca(2+) sparklets activated the
      prohypertensive calcineurin/NFATc3 signaling cascade. These events culminated in
      three hallmark signs of hypertension-associated vascular dysfunction: increased
      Ca(2+) entry, elevated arterial [Ca(2+)](i), and enhanced myogenic tone.
      Consistent with these observations, we show that PKCalpha ablation is protective
      against the development of angiotensin II-induced hypertension. These data
      support a model in which persistent Ca(2+) sparklets, PKCalpha, and calcineurin
      form a subcellular signaling triad controlling NFATc3-dependent gene expression,
      arterial function, and blood pressure. Because of the ubiquity of these proteins,
      this model may represent a general signaling pathway controlling gene expression
      and cellular function.

PMID- 18832166
TI  - Protein identification and quantification by two-dimensional infrared
      spectroscopy: implications for an all-optical proteomic platform.
AB  - Electron-vibration-vibration two-dimensional coherent spectroscopy, a variant of
      2DIR, is shown to be a useful tool to differentiate a set of 10 proteins based on
      their amino acid content. Two-dimensional vibrational signatures of amino acid
      side chains are identified and the corresponding signal strengths used to
      quantify their levels by using a methyl vibrational feature as an internal
      reference. With the current apparatus, effective differentiation can be achieved
      in four to five minutes per protein, and our results suggest that this can be
      reduced to <1 min per protein by using the same technology. Finally, we show that
      absolute quantification of protein levels is relatively straightforward to
      achieve and discuss the potential of an all-optical high-throughput proteomic
      platform based on two-dimensional infrared spectroscopic measurements.

PMID- 18832167
TI  - A procedure for highly specific, sensitive, and unbiased whole-genome
      amplification.
AB  - Highly specific amplification of complex DNA pools without bias or template
      independent products (TIPs) remains a challenge. We have developed a method using
      phi29 DNA polymerase and trehalose and optimized control of amplification to
      create micrograms of specific amplicons without TIPs from down to subfemtograms
      of DNA. With an input of as little as 0.5-2.5 ng of human gDNA or a few cells,
      the product could be close to native DNA in locus representation. The amplicons
      from 5 and 0.5 ng of DNA faithfully demonstrated all previously known
      heterozygous segmental duplications and deletions (3 Mb to 18 kb) located on
      chromosome 22 and even a homozygous deletion smaller than 1 kb with high
      resolution chromosome-wide comparative genomic hybridization. With 550k Infinium
      BeadChip SNP typing, the >99.7% accuracy was compared favorably with results on
      unamplified DNA. Importantly, underrepresentation of chromosome termini that
      occurred with GenomiPhi v2 was greatly rescued with the present procedure, and
      the call rate and accuracy of SNP typing were also improved for the amplicons
      with a 0.5-ng, partially degraded DNA input. In addition, the amplification
      proceeded logarithmically in terms of total yield before saturation; the intact
      cells was amplified >50 times more efficiently than an equivalent amount of
      extracted DNA; and the locus imbalance for amplicons with 0.1 ng or lower input
      of DNA was variable, whereas for higher input it was largely reproducible. This
      procedure facilitates genomic analysis with single cells or other traces of DNA,
      and generates products suitable for analysis by massively parallel sequencing as
      well as microarray hybridization.

PMID- 18832168
TI  - A minimalist network model for coarse-grained normal mode analysis and its
      application to biomolecular x-ray crystallography.
AB  - In this article, we report a method for coarse-grained normal mode analysis
      called the minimalist network model. The main features of the method are that it
      can deliver accurate low-frequency modes on structures without undergoing initial
      energy minimization and that it also retains the details of molecular
      interactions. The method does not require any additional adjustable parameters
      after coarse graining and is computationally very fast. Tests on modeling the
      experimentally measured anisotropic displacement parameters in biomolecular x-ray
      crystallography demonstrate that the method can consistently perform better than
      other commonly used methods including our own one. We expect this method to be
      effective for applications such as structural refinement and conformational
      sampling.

PMID- 18832169
TI  - Loss of Rb1 in the gastrointestinal tract of Apc1638N mice promotes tumors of the
      cecum and proximal colon.
AB  - To examine the role of Rb1 in gastrointestinal (GI) tumors, we generated mice
      with an Apc(1638N) allele, Rb(tm2brn) floxed alleles, and a villin-cre transgene
      (RBVCA). These animals had exon 19 deleted from Rb1 throughout the GI tract. We
      have shown previously that Rb1 deficiency is insufficient for GI tumor
      initiation, with inactivation of an Apc allele capable of overcoming the
      insufficiency. In this study we demonstrate that RBVCA mice have reduced median
      survival because of an increase in tumor incidence and multiplicity in the cecum
      and the proximal colon. Large intestinal tumors are predominantly adenomas,
      whereas the tumors of the small intestine are a mixture of adenomas and
      adenocarcinomas. We find truncation mutations to the second Apc allele in tumors
      of both the large and small intestine. Expression profiles of duodenal and cecal
      tumors relative to each other show unique gene subsets up and down regulated.
      Substantial expression patterns compare to human colorectal cancer, including
      recapitulation of embryonic genes. Our results indicate that Rb1 has significant
      influence over tumor location in the GI tract, and that both cecal and duodenal
      tumors initiate through inactivation of Apc. Expression profile analysis
      indicates the two tumor types differentially regulate distinct sets of genes that
      are over-expressed in a majority of human colorectal carcinomas.

PMID- 18832170
TI  - Synthesis of heterogeneous catalysts with well shaped platinum particles to
      control reaction selectivity.
AB  - Colloidal and sol-gel procedures have been used to prepare heterogeneous
      catalysts consisting of platinum metal particles with narrow size distributions
      and well defined shapes dispersed on high-surface-area silica supports. The
      overall procedure was developed in three stages. First, tetrahedral and cubic
      colloidal metal particles were prepared in solution by using a procedure derived
      from that reported by El-Sayed and coworkers [Ahmadi TS, Wang ZL, Green TC,
      Henglein A, El-Sayed MA (1996) Science 272:1924-1926]. This method allowed size
      and shape to be controlled independently. Next, the colloidal particles were
      dispersed onto high-surface-area solids. Three approaches were attempted: (i) in
      situ reduction of the colloidal mixture in the presence of the support, (ii) in
      situ sol-gel synthesis of the support in the presence of the colloidal particles,
      and (iii) direct impregnation of the particles onto the support. Finally, the
      resulting catalysts were activated and tested for the promotion of carbon-carbon
      double-bond cis-trans isomerization reactions in olefins. Our results indicate
      that the selectivity of the reaction may be controlled by using supported
      catalysts with appropriate metal particle shapes.

PMID- 18832171
TI  - BLyS inhibition eliminates primary B cells but leaves natural and acquired
      humoral immunity intact.
AB  - We have used an inhibiting antibody to determine whether preimmune versus antigen
      experienced B cells differ in their requisites for BLyS, a cytokine that controls
      differentiation and survival. Whereas in vivo BLyS inhibition profoundly reduced
      naive B cell numbers and primary immune responses, it had a markedly smaller
      effect on memory B cells and long-lived plasma cells, as well as secondary immune
      responses. There was heterogeneity within the memory pools, because IgM-bearing
      memory cells were sensitive to BLyS depletion whereas IgG-bearing memory cells
      were not, although both were more resistant than naive cells. There was also
      heterogeneity within B1 pools, as splenic but not peritoneal B1 cells were
      diminished by anti-BLyS treatment, yet the number of natural antibody-secreting
      cells remained constant. Together, these findings show that memory B cells and
      natural antibody-secreting cells are BLyS-independent and suggest that these
      pools can be separately manipulated.

PMID- 18832172
TI  - Hippocampal-dependent learning requires a functional circadian system.
AB  - Decades of studies have shown that eliminating circadian rhythms of mammals does
      not compromise their health or longevity in the laboratory in any obvious way.
      These observations have raised questions about the functional significance of the
      mammalian circadian system, but have been difficult to address for lack of an
      appropriate animal model. Surgical ablation of the suprachiasmatic nucleus (SCN)
      and clock gene knockouts eliminate rhythms, but also damage adjacent brain
      regions or cause developmental effects that may impair cognitive or other
      physiological functions. We developed a method that avoids these problems and
      eliminates rhythms by noninvasive means in Siberian hamsters (Phodopus sungorus).
      The present study evaluated cognitive function in arrhythmic animals by using a
      hippocampal-dependent learning task. Control hamsters exhibited normal circadian
      modulation of performance in a delayed novel-object recognition task. By
      contrast, arrhythmic animals could not discriminate a novel object from a
      familiar one only 20 or 60 min after training. Memory performance was not related
      to prior sleep history as sleep manipulations had no effect on performance. The
      GABA antagonist pentylenetetrazol restored learning without restoring circadian
      rhythms. We conclude that the circadian system is involved in memory function in
      a manner that is independent of sleep. Circadian influence on learning may be
      exerted via cyclic GABA output from the SCN to target sites involved in learning.
      Arrhythmic hamsters may have failed to perform this task because of chronic
      inhibitory signaling from the SCN that interfered with the plastic mechanisms
      that encode learning in the hippocampus.

PMID- 18832173
TI  - Notch1 regulates the fate of cardiac progenitor cells.
AB  - The Notch receptor mediates cell fate decision in multiple organs. In the current
      work we tested the hypothesis that Nkx2.5 is a target gene of Notch1 and raised
      the possibility that Notch1 regulates myocyte commitment in the adult heart.
      Cardiac progenitor cells (CPCs) in the niches express Notch1 receptor, and the
      supporting cells exhibit the Notch ligand Jagged1. The nuclear translocation of
      Notch1 intracellular domain (N1ICD) up-regulates Nkx2.5 in CPCs and promotes the
      formation of cycling myocytes in vitro. N1ICD and RBP-Jk form a protein complex,
      which in turn binds to the Nkx2.5 promoter initiating transcription and myocyte
      differentiation. In contrast, transcription factors of vascular cells are down
      regulated by Jagged1 activation of the Notch1 pathway. Importantly, inhibition of
      Notch1 in infarcted mice impairs the commitment of resident CPCs to the myocyte
      lineage opposing cardiomyogenesis. These observations indicate that Notch1 favors
      the early specification of CPCs to the myocyte phenotype but maintains the newly
      formed cells in a highly proliferative state. Dividing Nkx2.5-positive myocytes
      correspond to transit amplifying cells, which condition the replicative capacity
      of the heart. In conclusion, Notch1 may have critical implications in the control
      of heart homeostasis and its adaptation to pathologic states.

PMID- 18832174
TI  - Structure elucidation and biosynthesis of fuscachelins, peptide siderophores from
      the moderate thermophile Thermobifida fusca.
AB  - Bacteria belonging to the order Actinomycetales have proven to be an important
      source of biologically active and often therapeutically useful natural products.
      The characterization of orphan biosynthetic gene clusters is an emerging and
      valuable approach to the discovery of novel small molecules. Analysis of the
      recently sequenced genome of the thermophilic actinomycete Thermobifida fusca
      revealed an orphan nonribosomal peptide biosynthetic gene cluster coding for an
      unknown siderophore natural product. T. fusca is a model organism for the study
      of thermostable cellulases and is a major degrader of plant cell walls. Here, we
      report the isolation and structure elucidation of the fuscachelins, siderophore
      natural products produced by T. fusca. In addition, we report the purification
      and biochemical characterization of the termination module of the nonribosomal
      peptide synthetase. Biochemical analysis of adenylation domain specificity
      supports the assignment of this gene cluster as the producer of the fuscachelin
      siderophores. The proposed nonribosomal peptide biosynthetic pathway exhibits
      several atypical features, including a macrocyclizing thioesterase that produces
      a 10-membered cyclic depsipeptide and a nonlinear assembly line, resulting in the
      unique heterodimeric architecture of the siderophore natural product.

PMID- 18832175
TI  - Photochemistry and electron-transfer mechanism of transition metal oxalato
      complexes excited in the charge transfer band.
AB  - The photoredox reaction of trisoxalato cobaltate (III) has been studied by means
      of ultrafast extended x-ray absorption fine structure and optical transient
      spectroscopy after excitation in the charge-transfer band with 267-nm femtosecond
      pulses. The Co-O transient bond length changes and the optical spectra and
      kinetics have been measured and compared with those of ferrioxalate. Data
      presented here strongly suggest that both of these metal oxalato complexes
      operate under similar photoredox reaction mechanisms where the primary reaction
      involves the dissociation of a metal-oxygen bond. These results also indicate
      that excitation in the charge-transfer band is not a sufficient condition for the
      intramolecular electron transfer to be the dominant photochemistry reaction
      mechanism.

PMID- 18832176
TI  - Biomechanical ordering of dense cell populations.
AB  - The structure of bacterial populations is governed by the interplay of many
      physical and biological factors, ranging from properties of surrounding aqueous
      media and substrates to cell-cell communication and gene expression in individual
      cells. The biomechanical interactions arising from the growth and division of
      individual cells in confined environments are ubiquitous, yet little work has
      focused on this fundamental aspect of colony formation. We analyze the spatial
      organization of Escherichia coli growing in a microfluidic chemostat. We find
      that growth and expansion of a dense colony of cells leads to a dynamical
      transition from an isotropic disordered phase to a nematic phase characterized by
      orientational alignment of rod-like cells. We develop a continuum model of
      collective cell dynamics based on equations for local cell density, velocity, and
      the tensor order parameter. We use this model and discrete element simulations to
      elucidate the mechanism of cell ordering and quantify the relationship between
      the dynamics of cell proliferation and the spatial structure of the population.

PMID- 18832177
TI  - Dysfunction in ankyrin-B-dependent ion channel and transporter targeting causes
      human sinus node disease.
AB  - The identification of nearly a dozen ion channel genes involved in the genesis of
      human atrial and ventricular arrhythmias has been critical for the diagnosis and
      treatment of fatal cardiovascular diseases. In contrast, very little is known
      about the genetic and molecular mechanisms underlying human sinus node
      dysfunction (SND). Here, we report a genetic and molecular mechanism for human
      SND. We mapped two families with highly penetrant and severe SND to the human
      ANK2 (ankyrin-B/AnkB) locus. Mice heterozygous for AnkB phenocopy human SND
      displayed severe bradycardia and rate variability. AnkB is essential for normal
      membrane organization of sinoatrial node cell channels and transporters, and AnkB
      is required for physiological cardiac pacing. Finally, dysfunction in AnkB-based
      trafficking pathways causes abnormal sinoatrial node (SAN) electrical activity
      and SND. Together, our findings associate abnormal channel targeting with human
      SND and highlight the critical role of local membrane organization for sinoatrial
      node excitability.

PMID- 18832178
TI  - The splicing-factor oncoprotein SF2/ASF activates mTORC1.
AB  - The splicing factor SF2/ASF is an oncoprotein that is up-regulated in many
      cancers and can transform immortal rodent fibroblasts when slightly
      overexpressed. The mTOR signaling pathway is activated in many cancers, and
      pharmacological blockers of this pathway are in clinical trials as anticancer
      drugs. We examined the activity of the mTOR pathway in cells transformed by
      SF2/ASF and found that this splicing factor activates the mTORC1 branch of the
      pathway, as measured by S6K and eIF4EBP1 phosphorylation. This activation is
      specific to mTORC1 because no activation of Akt, an mTORC2 substrate, was
      detected. mTORC1 activation by SF2/ASF bypasses upstream PI3K/Akt signaling and
      is essential for SF2/ASF-mediated transformation, as inhibition of mTOR by
      rapamycin blocked transformation by SF2/ASF in vitro and in vivo. Moreover, shRNA
      mediated knockdown of mTOR, or of the specific mTORC1 and mTORC2 components
      Raptor and Rictor, abolished the tumorigenic potential of cells overexpressing
      SF2/ASF. These results suggest that clinical tumors with SF2/ASF up-regulation
      could be especially sensitive to mTOR inhibitors.

PMID- 18832179
TI  - Taxonomic and regional uncertainty in species-area relationships and the
      identification of richness hotspots.
AB  - Species-area relationships (SARs) are fundamental to the study of key and high
      profile issues in conservation biology and are particularly widely used in
      establishing the broad patterns of biodiversity that underpin approaches to
      determining priority areas for biological conservation. Classically, the SAR has
      been argued in general to conform to a power-law relationship, and this form has
      been widely assumed in most applications in the field of conservation biology.
      Here, using nonlinear regressions within an information theoretical model
      selection framework, we included uncertainty regarding both model selection and
      parameter estimation in SAR modeling and conducted a global-scale analysis of the
      form of SARs for vascular plants and major vertebrate groups across 792
      terrestrial ecoregions representing almost 97% of Earth's inhabited land. The
      results revealed a high level of uncertainty in model selection across biomes and
      taxa, and that the power-law model is clearly the most appropriate in only a
      minority of cases. Incorporating this uncertainty into a hotspots analysis using
      multimodel SARs led to the identification of a dramatically different set of
      global richness hotspots than when the power-law SAR was assumed. Our findings
      suggest that the results of analyses that assume a power-law model may be at
      severe odds with real ecological patterns, raising significant concerns for
      conservation priority-setting schemes and biogeographical studies.

PMID- 18832180
TI  - A Drosophila orphan G protein-coupled receptor BOSS functions as a glucose
      responding receptor: loss of boss causes abnormal energy metabolism.
AB  - Glucose, one of the most important nutrients for animals, acts as a regulatory
      signal that controls the secretion of hormones, such as insulin, by endocrine
      tissues. However, how organisms respond to extracellular glucose and how glucose
      controls nutrient homeostasis remain unknown. Here, we show that a putative
      Drosophila melanogaster G protein-coupled receptor, previously identified as
      Bride of sevenless (BOSS), responds to extracellular glucose and regulates sugar
      and lipid metabolism. We found that BOSS was expressed in the fat body, a
      nutrient-sensing tissue equivalent to mammalian liver and adipose tissues, and in
      photoreceptor cells. Boss null mutants had small bodies, exhibited abnormal sugar
      and lipid metabolism (elevated circulating sugar and lipid levels, impaired lipid
      mobilization to oenocytes), and were sensitive to nutrient deprivation stress.
      These phenotypes are reminiscent of flies defective in insulin signaling.
      Consistent with these findings are the observations that boss mutants had reduced
      PI3K activity and phospho-AKT levels, which indicates that BOSS is required for
      proper insulin signaling. Because human G protein-coupled receptor 5B and the
      seven-transmembrane domain of BOSS share the same sequence, our results also have
      important implications for glucose metabolism in humans. Thus, our study provides
      insight not only into the basic mechanisms of metabolic regulation but also into
      the pathobiological basis for diabetes and obesity.

PMID- 18832181
TI  - Distinct microRNA expression profiles in acute myeloid leukemia with common
      translocations.
AB  - MicroRNAs (miRNAs) are postulated to be important regulators in cancers. Here, we
      report a genome-wide miRNA expression analysis in 52 acute myeloid leukemia (AML)
      samples with common translocations, including t(8;21)/AML1(RUNX1)-ETO(RUNX1T1),
      inv(16)/CBFB-MYH11, t(15;17)/PML-RARA, and MLL rearrangements. Distinct miRNA
      expression patterns were observed for t(15;17), MLL rearrangements, and core
      binding factor (CBF) AMLs including both t(8;21) and inv(16) samples. Expression
      signatures of a minimum of two (i.e., miR-126/126*), three (i.e., miR-224, miR
      368, and miR-382), and seven (miR-17-5p and miR-20a, plus the aforementioned
      five) miRNAs could accurately discriminate CBF, t(15;17), and MLL-rearrangement
      AMLs, respectively, from each other. We further showed that the elevated
      expression of miR-126/126* in CBF AMLs was associated with promoter demethylation
      but not with amplification or mutation of the genomic locus. Our gain- and loss
      of-function experiments showed that miR-126/126* inhibited apoptosis and
      increased the viability of AML cells and enhanced the colony-forming ability of
      mouse normal bone marrow progenitor cells alone and particularly, in cooperation
      with AML1-ETO, likely through targeting Polo-like kinase 2 (PLK2), a tumor
      suppressor. Our results demonstrate that specific alterations in miRNA expression
      distinguish AMLs with common translocations and imply that the deregulation of
      specific miRNAs may play a role in the development of leukemia with these
      associated genetic rearrangements.

PMID- 18832182
TI  - Nickel and the microbial toxin, MALP-2, stimulate proangiogenic mediators from
      human lung fibroblasts via a HIF-1alpha and COX-2-mediated pathway.
AB  - Hypoxia-inducible factor (HIF-1alpha) and cyclooxygenase-2 (COX-2) have been
      implicated in the regulation of inflammatory-like processes that lead to
      angiogenesis and fibrotic disorders. Here we demonstrate that in human lung
      fibroblasts (HLFs) treated with mixed exposures to chemical and microbial
      stimuli, HIF-1alpha stabilization plays a pivotal role in the induction of COX-2
      mRNA and protein, driving the release of vascular endothelial growth factor
      (VEGF) and proangiogenic and profibrotic chemokines. Upon costimulation with Ni
      and the mycoplasma-derived lipopeptide macrophage-activating lipopeptide-2 (MALP
      2), there was a synergistic induction of CXCL1 and CXCL5 mRNA and protein release
      from HLF, as well as an enhanced response in VEGF compared to either stimulus
      alone. Consistent with our previous findings that Ni and MALP-2 stimulates the
      induction of CXCL8 via a COX-2-mediated pathway, CXCL1, CXCL5, and VEGF release
      were also regulated by COX-2. Ni induced the stabilization of HIF-1alpha protein
      in HLF, which was further enhanced in the presence of MALP-2. Depletion of HIF
      1alpha using siRNA blocked COX-2 induction by Ni and MALP-2 along with the
      release of VEGF, CXCL1, CXCL5, and CXCL8. Our results indicate that Ni and MALP-2
      interact to promote an angiogenic profibrotic phenotype in HLF. Moreover, these
      findings reveal a potential role for HIF-1alpha in mediating chemical-induced
      alterations in cellular response to microbial stimuli, modulating pulmonary
      inflammation and its consequences such as fibrosis and angiogenesis.

PMID- 18832183
TI  - A concentration addition model for the activation of the constitutive androstane
      receptor by xenobiotic mixtures.
AB  - The effects of contaminants are typically studied in individual exposures;
      however, environmental exposures are rarely from a single contaminant. Therefore,
      the study of chemical mixtures is important in determining the effects of
      xenobiotics. The constitutive androstane receptor (CAR) responds to endobiotics
      and xenobiotics, and in turn induces detoxification enzymes involved in their
      elimination. First, we compared several androgens as inverse agonists, including
      androgens allegedly used by Bay Area Laboratory Co-operative to enhance athletic
      performance. CAR inverse agonists ranked in order of potency were
      dihydroandrosterone (DHA) > tetrahydrogestrinone (THG) > androstanol >
      norbolethone. Therefore, we used DHA as an inverse agonist during transactivation
      assays. Next, we examined the effects of several pesticides, plasticizers,
      steroids, and bile acids on CAR activation. Our data demonstrates that several
      pesticides and plasticizers, including diethylhexylphthalate, nonylphenol,
      cypermethrin, and chlorpyrifos activate CAR. Both full and partial CAR activators
      were discovered, and EC(50) values and Hillslopes were determined for use in the
      concentration addition models. Concentration addition models with and without
      restraint values to account for partial activators were developed. Measured
      results from transactivation assays with a mixture of two to five chemicals
      indicate that the concentration addition model without restraints correctly
      predicts activity unless all of the chemicals in the mixture are partial
      activators, and then restraint values be considered. Overall, our data indicates
      that it is important to consider that we are exposed to a milieu of chemicals,
      and the efficacy of each individual chemical is not the sole factor in
      determining CAR's activity in mixture modeling.

PMID- 18832184
TI  - Filling the concept with data: integrating data from different in vitro and in
      silico assays on skin sensitizers to explore the battery approach for animal-free
      skin sensitization testing.
AB  - Tests for skin sensitization are required prior to the market launch of new
      cosmetic ingredients. Significant efforts are made to replace the current animal
      tests. It is widely recognized that this cannot be accomplished with a single in
      vitro test, but that rather the integration of results from different in vitro
      and in silico assays will be needed for the prediction of the skin sensitization
      potential of chemicals. This has been proposed as a theoretical scheme so far,
      but no attempts have been made to use experimental data to prove the validity of
      this concept. Here we thus try for the first time to fill this widely cited
      concept with data. To this aim, we integrate and report both novel and literature
      data on 116 chemicals of known skin sensitization potential on the following
      parameters: (1) peptide reactivity as a surrogate for protein binding, (2)
      induction of antioxidant/electrophile responsive element dependent luciferase
      activity as a cell-based assay; (3) Tissue Metabolism Simulator skin
      sensitization model in silico prediction; and (4) calculated octanol-water
      partition coefficient. The results of the in vitro assays were scaled into five
      classes from 0 to 4 to give an in vitro score and compared to the local lymph
      node assay (LLNA) data, which were also scaled from 0 to 4
      (nonsensitizer/weak/moderate/strong/extreme). Different ways of evaluating these
      data have been assessed to rate the hazard of chemicals (Cooper statistics) and
      to also scale their potency. With the optimized model an overall accuracy for
      predicting sensitizers of 87.9% was obtained. There is a linear correlation
      between the LLNA score and the in vitro score. However, the correlation needs
      further improvement as there is still a relatively high variation in the in vitro
      score between chemicals belonging to the same sensitization potency class.

PMID- 18832185
TI  - The 2,2',4,4',5,5'-hexachlorobiphenyl-enhanced degradation of connexin 43
      involves both proteasomal and lysosomal activities.
AB  - One of the toxic effects of non-dioxin-like polychlorinated biphenyls (NDL-PCBs)
      is the acute inhibition of gap junctional intercellular communication (GJIC), an
      event possibly associated with tumor promotion. The model NDL-PCB-2,2',4,4',5,5'
      hexachlorobiphenyl (PCB 153)-induces a sustained GJIC inhibition in rat liver
      epithelial WB-F344 cells. As this effect might be related to deregulation of
      connexin 43 (Cx43) synthesis, trafficking, or degradation, we investigated the
      impact of PCB 153 on these events. Although PCB 153 had no effect on Cx43 mRNA
      levels, it induced a gradual loss of Cx43 protein and significantly decreased the
      amount of gap junction plaques in plasma membrane. PCB 153 contributed to
      extracellular signal-regulated kinases 1 and 2 (ERK1/2)-dependent accumulation of
      hyperphosphorylated Cx43-P3 form, thus indicating that ERK1/2 activation by PCB
      153 might contribute to its effects on Cx43 internalization or degradation.
      Inhibition of either proteasomes or lysosomes with their specific inhibitors
      largely restored total Cx43 protein levels, thus suggesting that both proteasomes
      and lysosomes may participate in the PCB 153-enhanced Cx43 internalization and
      degradation. However, neither the proteasomal nor the lysosomal inhibitors
      restored normal GJIC or number/size of gap junction plaques. Finally, PCB 153
      also interfered with restoration of gap junction plaques following the inhibition
      of Cx43 transport to plasma membrane. Taken together, multiple modes of action
      seem to contribute to downregulation of Cx43 in PCB 153-treated rat liver
      epithelial cells. The enhanced degradation of Cx43, together with persistent
      inhibition of GJIC, might contribute to tumor-promoting effects of NDL-PCBs.

PMID- 18832186
TI  - A novel, cellulose synthesis inhibitory action of ancymidol impairs plant cell
      expansion.
AB  - The co-ordination of cell wall synthesis with plant cell expansion is an
      important topic of contemporary plant biology research. In studies of cell wall
      synthesis pathways, cellulose synthesis inhibitors are broadly used. It is
      demonstrated here that ancymidol, known as a plant growth retardant primarily
      affecting gibberellin biosynthesis, is also capable of inhibiting cellulose
      synthesis. Its ability to inhibit cellulose synthesis is not related to its anti
      gibberellin action and possesses some unique features never previously observed
      when conventional cellulose synthesis inhibitors were used. It is suggested that
      ancymidol targets the cell wall synthesis pathway at a regulatory step where cell
      wall synthesis and cell expansion are coupled. The elucidation of the ancymidol
      target in plant cells could potentially contribute to our understanding of cell
      wall synthesis and cell expansion control.

PMID- 18832187
TI  - Phylogeny, gene structures, and expression patterns of the ERF gene family in
      soybean (Glycine max L.).
AB  - Members of the ERF transcription factor family play important roles in regulating
      gene expression in response to biotic and abiotic stresses. In soybean (Glycine
      max L.), however, only a few ERF genes have been studied so far. In this study,
      98 unigenes that contained a complete AP2/ERF domain were identified from 63,676
      unique sequences in the DFCI Soybean Gene Index database. The phylogeny, gene
      structures, and putative conserved motifs in soybean ERF proteins were analysed,
      and compared with those of Arabidopsis and rice. The members of the soybean ERF
      family were divided into 12 subgroups, similar to the case for Arabidopsis.
      AP2/ERF domains were conserved among soybean, Arabidopsis, and rice. Outside the
      AP2/ERF domain, many soybean-specific conserved motifs were detected. Expression
      analysis showed that nine unigenes belonging to six ERF family subgroups were
      induced by both biotic/abiotic stresses and hormone treatment, suggesting that
      they were involved in cross-talk between biotic and abiotic stress-responsive
      signalling pathways. Overexpression of two full-length genes from two different
      subgroups enhanced the tolerances to drought, salt stresses, and/or pathogen
      infection of the tobacco plants. These results will be useful for elucidating ERF
      gene-associated stress response signalling pathways in soybean.

PMID- 18832188
TI  - Exposure to nitric oxide protects against oxidative damage but increases the
      labile iron pool in sorghum embryonic axes.
AB  - Sodium nitroprusside (SNP) and diethylenetriamine NONOate (DETA NONOate), were
      used as the source of exogenous NO to study the effect of NO upon germination of
      sorghum (Sorghum bicolor (L.) Moench) seeds through its possible interaction with
      iron. Modulation of cellular Fe status could be an important factor for the
      establishment of oxidative stress and the regulation of plant physiology. Fresh
      and dry weights of the embryonic axes were significantly increased in the
      presence of 0.1 mM SNP, as compared to control. Spin trapping EPR was used to
      assess the NO content in axes from control seeds after 24 h of imbibition (2.4+/
      0.2 nmol NO g(-1) FW) and seeds exposed to 0.01, 0.1, and 1 mM SNP (3.1+/-0.3,
      4.6+/-0.2, and 6.0+/-0.9 nmol NO g(-1) FW, respectively) and 1 mM DETA NONOate
      (6.2+/-0.6 nmol NO g(-1) FW). Incubation of seeds with 1 mM SNP protected against
      oxidative damage to lipids and maintained membrane integrity. The content of the
      deferoxamine-Fe (III) complex significantly increased in homogenates of axes
      excised from seeds incubated in the presence of 1 mM SNP or 1 mM DETA NONOate as
      compared to the control (19+/-2 nmol Fe g(-1) FW, 15.2+/-0.5 nmol Fe g(-1) FW,
      and 8+/-1 nmol Fe g(-1) FW, respectively), whereas total Fe content in the axes
      was not affected by the NO donor exposure. Data presented here provide
      experimental evidence to support the hypothesis that increased availability of NO
      drives not only protective effects to biomacromolecules, but to increasing the Fe
      availability for promoting cellular development as well.

PMID- 18832189
TI  - Homeostatic control of slow vacuolar channels by luminal cations and evaluation
      of the channel-mediated tonoplast Ca2+ fluxes in situ.
AB  - Ca(2+), Mg(2+), and K(+) activities in red beet (Beta vulgaris L.) vacuoles were
      evaluated using conventional ion-selective microelectrodes and, in the case of
      Ca(2+), by non-invasive ion flux measurements (MIFE) as well. The mean vacuolar
      Ca(2+) activity was approximately 0.2 mM. Modulation of the slow vacuolar (SV)
      channel voltage dependence by Ca(2+) in the absence and presence of other cations
      at their physiological concentrations was studied by patch-clamp in excised
      tonoplast patches. Lowering pH at the vacuolar side from 7.5 to 5.5 (at zero
      vacuolar Ca(2+)) did not affect the channel voltage dependence, but abolished
      sensitivity to luminal Ca(2+) within a physiological range of concentrations (0.1
      1.0 mM). Aggregation of the physiological vacuolar Na(+) (60 mM) and Mg(2+) (8
      mM) concentrations also results in the SV channel becoming almost insensitive to
      vacuolar Ca(2+) variation in a range from nanomoles to 0.1 mM. At physiological
      cation concentrations at the vacuolar side, cytosolic Ca(2+) activates the SV
      channel in a voltage-independent manner with K(d)=0.7-1.5 microM. Comparison of
      the vacuolar Ca(2+) fluxes measured by both the MIFE technique and from
      estimating the SV channel activity in attached patches, suggests that, at resting
      membrane potentials, even at elevated (20 microM) cytosolic Ca(2+), only 0.5% of
      SV channels are open. This mediates a Ca(2+) release of only a few pA per vacuole
      (approximately 0.1 pA per single SV channel). Overall, our data suggest that the
      release of Ca(2+) through SV channels makes little contribution to a global
      cytosolic Ca(2+) signal.

PMID- 18832190
TI  - Evaluation of the variable anchorage straightwire technique using Ricketts'
      growth prediction.
AB  - The purpose of this retrospective study was to evaluate the treatment effects of
      the variable anchorage straightwire technique (VAST) in Angle Class II patients
      using Ricketts' growth prediction analysis. The subjects belonged to two groups:
      a control, consisting of 30 untreated Class II Swedish individuals (20 girls, 10
      boys) with a mean age of 11.2 years, and the other 29 Swedish patients (14 girls,
      15 boys), mean age 12.6 years, post-normal and with an increased overbite (OB),
      treated with the VAST. Two lateral cephalograms were available for every
      individual. Growth prediction according to Ricketts' visual treatment objective
      (VTO) was used to estimate the expected growth increments for a 2-year period. It
      was first used in the control group to determine its validity and then applied to
      the treated group to evaluate the net effects of treatment. Cephalometric
      evaluation based on Ricketts' analysis and additional dentoalveolar variables
      were carried out. Statistical analysis was undertaken using a paired Student's t-
      and Wilcoxon signed ranks tests. The method of predicting growth according to the
      VTO was, in general, valid in the untreated subjects, apart from the inclination
      of the lower incisors, where the proclination had been underestimated. In the
      treated group, the net effects of treatment were significant for the
      dentoalveolar variables: reduction of overjet (OJ) and OB, proclination and
      relative intrusion of the lower incisors, extrusion of the molars, and increase
      in lower face height. The growth prediction method according to VTO was found to
      be valid in a sample of Swedish post-normal children concerning skeletal and
      dentoalveolar variables. The VAST treatment net effects in these growing patients
      were achieved mainly by dentoalveolar changes.

PMID- 18832191
TI  - Commentary: tumor growth, patient survival, and the search for the optimal phase
      II efficacy endpoint.

PMID- 18832192
TI  - Catalytically active peptidylglycine alpha-amidating monooxygenase in the media
      of androgen-independent prostate cancer cell lines.
AB  - Peptidylglycine alpha-amidating monooxygenase (PAM) converts inactive terminal
      glycine prohormones into their activated alpha-amidated forms. PAM is thought to
      play a role in the development of antiandrogen drug resistance in prostate cancer
      (CaP) through PAMactivated autocrine growth. On the basis of the previous finding
      that many lung cancer cell lines excrete PAM into their culture media, this study
      investigates PAM levels in media collected from human CaP cell line cultures.
      Androgen-independent DU145 and PC-3 prostate cancer cell lines exhibited readily
      detectable levels of PAM activity in extracts and media, whereas the androgen
      dependent LNCaP cell line showed little or no activity. Because of the much
      larger volume of media versus cell extracts, more than 90% of the total PAM
      activity was located in the media for both the PC-3 and DU145 cell lines,
      providing a readily accessible source of CaP PAM. A simple, scalable method to
      obtain PAM from the culture media of androgen-independent human prostate cancer
      cell lines is described in this article. This approach provides a much easier
      means of collecting CaP-derived PAM than previously described cell fractionation
      procedures and should facilitate the investigations of the role and targeting of
      PAM in hormone-independent CaP.

PMID- 18832193
TI  - Template-directed self-assembly enhances RTK catalytic domain function.
AB  - Receptor tyrosine kinases have become important therapeutic targets because of
      their involvement in diseases, including cancer. Kinase domains, which are
      soluble and easily purified, have found widespread use in enzyme inhibitor
      assays, but these domains do not exhibit full function because they are isolated
      from the membrane. To address this shortcoming, the authors developed a simple
      method to restore biologically relevant function by assembling kinase domains on
      a nanometer-scale template, which imitates the membrane surface.
      Autophosphorylation of template-assembled tyrosine kinase domains from the
      insulin, EphB2, and Tie2 receptors led to substantially larger phosphorylation
      levels compared with domains assayed under conventional conditions. Template
      directed assembly increased the total substrate phosphorylation of the insulin
      and EphB2 receptor kinase domains as much as 60-fold and 15-fold, respectively.
      In contrast, substrate phosphorylation by template-assembled Tie2 was much lower
      than conventional conditions. The lower activity observed with the template is
      more biologically relevant because autophosphorylation of Tie2 is self
      inhibitory. These results, as well as the underlying similarity between the
      organization of template-assembled and natural membrane signaling environments,
      suggest that template-directed assembly of signaling proteins will provide
      widespread benefit to basic and applied signal transduction research, especially
      drug discovery.

PMID- 18832194
TI  - Letter to the editor: "Brain drain" and loss of resources jeopardize the
      continued use of domestic animals for agricultural and biomedical research.

PMID- 18832195
TI  - Invited review: crossbreeding in dairy cattle from a German perspective of the
      past and today.
AB  - Several crossing experiments in dairy cattle are currently in progress. Most of
      them are based on Holstein-Friesian, superior in milk production, and Jersey,
      known for highly concentrated milk and early maturity. Crossbreeding can lead to
      combination of favorable characteristics from the breeds involved, based on breed
      additive genetic effects. Further, heterosis can be of additional economic
      benefit, but the magnitude of heterosis is not well established for many breed
      combinations, and traits and effects of heterosis are not heritable. These
      unknowns, and possible recombination losses in rotational crossbreeding systems,
      are the challenges to practical application of crossbreeding in dairy cattle.
      Crossbreeding, if widely implemented, impacts existing breeding schemes and
      should be pursued after careful economic evaluation. In the former East Germany,
      crossbreeding in dairy cattle led to a new synthetic breed, a milk-emphasized
      dual-purpose breed called Schwarzbuntes Milchrind der DDR (SMR). The SMR
      composite was based on a 3-breed cross, including native East German Black and
      White, Danish Jersey, and Canadian Holstein-Friesian. The SMR breed was used in
      commercial milk production in East Germany in the 1970s and 1980s. This paper
      describes the goals in creating and performance of SMR and summarizes related
      work during the SMR period. Current German crossing experiments and profitability
      for different amounts of heterosis will be introduced.

PMID- 18832196
TI  - Development and optimization of a carbon dioxide-aided cold microfiltration
      process for the physical removal of microorganisms and somatic cells from skim
      milk.
AB  - Physical removal of microorganisms from skim milk by microfiltration (MF) is
      becoming increasingly attractive to the dairy industry. Typically, this process
      is performed at temperatures of approximately 50 degrees C. Additional shelf-life
      and quality benefits might be gained by conducting the MF process at low
      temperatures. Cold MF could also minimize microbial fouling of the membrane and
      prevent the germination of thermophilic spores. The objective of this study was
      to optimize a cold MF process for the effective removal of microbial and somatic
      cells from skim milk. An experimental MF setup containing a tubular Tami ceramic
      membrane with a nominal pore size of 1.4 microm was used for MF of raw skim milk
      at a temperature of 6 +/- 1 degrees C. The processing conditions used were cross
      flow velocities of 5 to 7 m/s, and transmembrane pressures of 52 to 131 kPa. All
      MF experiments were performed in triplicate. The permeate flux was determined
      gravimetrically. Microbiological, chemical, and somatic cell analyses were
      performed to evaluate the effect of MF on the composition of skim milk. The
      permeate flux increased drastically when velocity was increased from 5 to 7 m/s.
      The critical transmembrane pressure range conducive to maximum fluxes was 60 to
      85 kPa. When MF was conducted under optimal conditions, very efficient removal of
      vegetative bacteria, spores, and somatic cells, as well as near complete
      transmission of proteins into the MF milk, was achieved. To further enhance the
      flux, a CO(2) backpulsing system was developed. This technique is able both to
      increase the flux and to maintain it steadily for an extended period of time. The
      CO(2)-aided cold MF process has the potential to become economically attractive
      to the dairy industry, with direct benefits for the quality and shelf life of
      dairy products.

PMID- 18832197
TI  - Manufacture of acid gels from skim milk using high-pressure homogenization.
AB  - The effect of high-pressure homogenization (HPH) alone or in combination with a
      thermal treatment (TT) was investigated for the manufacture of acid gels from
      skim milk. Raw skim milk was subjected to HPH (0 to 350 MPa) or a TT (90 degrees
      C, 5 min), or both, in the following processing combinations: 1) HPH, 2) HPH
      followed by TT, 3) TT followed by HPH, 4) TT, and 5) raw milk (control). After
      treatments, L* (lightness) values were measured, and then skim milk was acidified
      with 3% glucono-delta-lactone and rheological properties (G' and gelation time),
      and whey holding capacity was evaluated. Treatments in which HPH and TT were
      combined showed greater L* values than those in which just HPH was applied. In
      all treatments, the L* values decreased as the pressure was increased up to 300
      MPa with little change afterward. Gelation times were lower when HPH was combined
      with TT compared with the acid skim milk gels that were just pressure treated.
      The final G' in gels obtained from skim milk subjected to the combined process
      (HPH and TT) was greater and pressure-dependent compared with all other gels. A
      maximum G' (~320 Pa) was observed with skim milk subjected to a combination of
      thermal processing before or after HPH at 350 MPa. Acid gels obtained from HPH
      milk at 350 MPa showed a linear decrease in whey holding capacity over time,
      retaining 20% more whey after centrifugation for 25 min compared with samples
      treated at lower pressures and all other treatments. Our results suggest that HPH
      in combination with TT can be used to improve the rheological properties and
      stability of yogurt, thus decreasing the need for additives.

PMID- 18832198
TI  - Bovine milk glycome.
AB  - Bovine milk oligosaccharides have several potentially important biological
      activities including the prevention of pathogen binding to the intestinal
      epithelial and as nutrients for beneficial bacteria. It has been suggested that
      milk oligosaccharides are an important source of complex carbohydrates as
      supplements for the food and the pharmaceutical industries. However, only a small
      number of structures of bovine milk oligosaccharides (bMO) are known. There have
      been no systematic studies on bMO. High-performance mass spectrometry and
      separation methods are used to evaluate bMO, and nearly 40 oligosaccharides are
      present in bovine milk. Bovine milk oligosaccharides are composed of shorter
      oligomeric chains than are those in human milk. They are significantly more
      anionic with nearly 70%, measured abundances, being sialylated. Additionally, bMO
      are built not only on the lactose core (as are nearly all human milk
      oligosaccharides), but also on lactose amines. Sialic acid residues include both
      N-acetyl and N-glycolylneuraminic acid, although the former is significantly more
      abundant.

PMID- 18832199
TI  - Evaluation of molecular methods for the detection of Brucella species in water
      buffalo milk.
AB  - Brucellosis is a highly infectious disease affecting both animals and humans. The
      current standard tools for the diagnosis of this bacterial infection are
      serological and microbiological. In this study, we evaluated the feasibility of
      molecular assays as diagnostic tools for the detection of Brucella spp. in water
      buffalo milk. For this purpose, we first compared different DNA extraction
      protocols and PCR methods on artificially spiked milk samples. The most sensitive
      methods were then used to examine milk from serologically positive and negative
      water buffaloes. Molecular results were compared with serological and
      bacteriological test results. Milk samples from 53 Brucella seropositive
      buffaloes (by either rose Bengal or complement fixation test) were positive by
      ELISA, 37 were positive by culture, 33 were positive by PCR, and 35 were positive
      by real-time PCR. Of the 37 culture-positive samples, a total of 25 and 26 were
      positive by PCR and real-time PCR, respectively. Of the 16 culture-negative
      samples, 8 were positive by PCR and 9 by real-time PCR. Thus, although culture
      showed greater sensitivity than PCR, some animals found positive by serological
      methods and PCR tested negative by milk culture. The combined use of
      bacteriological and molecular tools increased the number of positive samples to
      46. In conclusion, these results suggest that the simultaneous application of
      these 2 direct detection methods (culture and PCR) could be more useful than one
      test alone for the diagnosis of Brucella spp. in buffalo milk.

PMID- 18832200
TI  - Effect of minor milk proteins in chymosin separated whey and casein fractions on
      cheese yield as determined by proteomics and multivariate data analysis.
AB  - The objective of this work was to find regressions between minor milk proteins or
      protein fragments in the casein or sweet whey fraction and cheese yield because
      the effect of major milk proteins was evaluated in a previous study. Proteomic
      methods involving 2-dimensional gel electrophoresis and mass spectrometry in
      combination with multivariate data analysis were used to study the effect of
      variations in milk protein composition in chymosin separated whey and casein
      fractions on cheese yield. By mass spectrometry, a range of proteins significant
      for the cheese yield was identified. Among others, a C-terminal fragment of beta
      casein had a positive effect on the cheese yield expressed as grams of cheese per
      100 g of milk, whereas several other minor fragments of beta-, alpha(s1)-, and
      alpha(s2)-casein had positive effects on the transfer of protein from milk to
      cheese. However, the individual effect of each identified protein was relatively
      low. Therefore, further studies of the relations between different
      proteins/peptides in the rennet casein or sweet whey fractions and cheese yield
      are needed for advanced understanding and prediction of cheese yield.

PMID- 18832201
TI  - Identification of yeasts and evaluation of their distribution in Taiwanese Kefir
      and Viili starters.
AB  - The objective of the present study was to investigate yeast communities in kefir
      grains and viili starters in Taiwan through conventional microbiological
      cultivation and polymerase chain reaction-denaturing gradient gel electrophoresis
      (PCR-DGGE). The DNA sequencing was used as a validity technique to ensure that
      all isolates within each group belonged to just one species, and to confirm the
      identified results of PCR-DGGE. Results indicated that a combination of
      conventional microbiological cultivation with PCR-DGGE and sequencing could
      successfully identify 4 yeast species from both types of cultures in Taiwan.
      Kluyveromyces marxianus, Saccharomyces turicensis, and Pichia fermentans were
      found in Taiwanese kefir grains with a distribution of 76, 22, and 2%,
      respectively, whereas Klu. marxianus, Saccharomyces unisporus and P. fermentans
      were identified in viili starters corresponding to 58, 11, and 31% of the total
      cell counts, respectively. Furthermore, the culture-independent method was
      applied to identify the yeast species using DGGE. Only 2 yeast species, Klu.
      marxianus and S. turicensis, were found in kefir grains and 2, Klu. marxianus and
      P. fermentans, in viili starters. These results suggest that in samples
      containing multiple species, PCR-DGGE may fail to detect some species. Sequences
      of yeast isolates reported in this study have been deposited in the GenBank
      database under accession nos. DQ139802, AF398485, DQ377652, and AY007920.

PMID- 18832202
TI  - Short communication: impact of pH and temperature on the acidifying activity of
      Carnobacterium maltaromaticum.
AB  - The acidifying activity of Carnobacterium maltaromaticum LMA28, a strain isolated
      from French soft cheese, was studied in trypticase soy broth with yeast extract
      (TSB-YE) medium and in milk. In TSB-YE supplemented with lactose, glucose, or
      galactose, lactose and glucose were metabolized with a maximum growth rate of
      0.32 h(-1) and galactose was not metabolized. During hydrolysis of lactose, the
      galactose moiety was not excreted. The major product was l(+) lactic acid, with
      no significant difference in the lactic acid yield. Glucose was not completely
      metabolized because cell growth stopped when pH values reached an average of 5.0.
      In sterilized UHT milk, the addition of 1 g/L of YE enhanced its coagulation.
      Compared with commercial starter lactic acid bacteria such as Lactococcus lactis
      DSMZ 20481 or Streptococcus thermophilus INRA 302, Carnobacterium maltaromaticum
      LMA 28 was shown to be a slow acidifying strain. However, in spite of this weak
      acidifying ability, C. maltaromaticum LMA 28 can sustain low pH values in
      coculture with Lc. lactis DSMZ 20481 or S. thermophilus INRA 302. The individual
      and interactive effects of initial pH values (5.2 to 8.0) and incubation
      temperatures (23 to 37 degrees C) on acidifying activity were studied by response
      surface methodology. The 3 strains displayed different behaviors depending on pH
      and temperature. The psychrotrophic lactic acid strain C. maltaromaticum LMA 28
      was able to grow at alkaline pH values and during storage conditions. It could be
      used as a potential ripening flora in soft cheese.

PMID- 18832203
TI  - Nutrition, metabolism, and fertility in dairy cows: 1. Dietary energy source and
      ovarian function.
AB  - In previous studies, high plasma insulin was associated with earlier resumption
      of postpartum estrous cycles in dairy cows. The objective of this experiment was
      to quantify hormonal and ovarian responses to dietary starch and fat contents.
      Thirty cows were fed on a standard diet from calving until 40 d in milk (DIM) and
      then 6 cows were allocated to each of 5 isoenergetic diets containing 231, 183,
      159, 135, and 87 g of starch and 39, 42, 43, 45, and 48 g of fat/kg of dry matter
      (DM) for diets 1 to 5, respectively, until 70 DIM. Estrus was synchronized at 60
      DIM. Between 60 and 70 DIM, energy intake, milk yield, and energy balance were
      similar among diet groups. Plasma insulin-to-glucagon ratio increased with
      increasing dietary starch and decreasing dietary fat concentrations, reaching a
      break point at 159 g of starch, 43 g of fat/kg of DM (diets 1 to 5: mean 3.86,
      3.78, 3.59, 2.98, 2.06 +/- standard error 0.22). Growth hormone, insulin-like
      growth factor-I, and leptin did not vary among diets. The greatest dietary starch
      concentration was associated with elevated plasma urea-N (diets 1 to 5: mean
      3.69, 3.01, 2.94, 2.95, 2.75, +/- standard error 0.13 mmol/L, respectively) and
      delayed postovulatory progesterone increase (progesterone at 3 to 5 d
      postovulation for diets 1 to 5: mean 2.7, 5.9, 4.2, 5.6, 4.3 +/- standard error
      0.9 ng/mL, respectively). The number of small (<5 mm) ovarian follicles was
      positively related to starch intake (r = 0.381) and plasma insulin concentration
      (r = 0.402). It is concluded that to maintain adequate insulin-to-glucagon ratio
      in cows at the start of the breeding period, dietary starch concentration should
      be above 160 g/kg of DM and dietary fat below 44 g/kg of DM, and this should have
      a positive effect on ovarian function.

PMID- 18832204
TI  - Nutrition, metabolism, and fertility in dairy cows: 2. Dietary fatty acids and
      ovarian function.
AB  - Plasma insulin has important implications for ovarian function in dairy cows.
      Previous work demonstrated that plasma insulin increased with increasing dietary
      starch and decreasing dietary fatty acid concentrations. The objective of this
      experiment was to investigate hormonal and ovarian responses to dietary fatty
      acid content with no change in other dietary components. Thirty cows were fed a
      standard diet from calving until 40 d in milk (DIM) and then 6 cows were
      transferred to each of 5 diets containing 0, 8, 15, 23, and 30 g/kg of dry matter
      (DM) of calcium salts of palm fatty acids (CaPFA; Megalac) until 70 DIM. Estrus
      was synchronized at 60 DIM. Between 60 and 70 DIM, energy intake, milk yield, and
      energy balance were similar among diet groups. Plasma insulin decreased when
      dietary concentration of CaPFA exceeded 15 g/kg of DM (insulin: 0.46, 0.41, 0.46,
      0.33, 0.28 +/- SE 0.034 ng/mL for diets containing 0 to 30 g of CaPFA/kg of DM,
      respectively). Maximum plasma insulin to glucagon ratio was observed with 15 g of
      CaPFA/kg of DM (ratios: 3.99, 4.33, 4.67, 3.45, 2.89 +/- SE 0.156 for diets
      containing 0 to 30 g of CaPFA/kg of DM, respectively). Plasma concentrations of
      growth hormone, insulin-like growth factor-I and leptin did not vary between
      diets. The number of small (<5 mm) ovarian follicles was negatively related to
      plasma insulin concentration (r = -0.328) and was stimulated by CaPFA
      supplementation at all rates tested compared with cows receiving zero CaPFA
      (small follicles preovulation: 6.7, 11.2, 11.5, 11.3, 11.9 +/- SE 1.48 for diets
      containing 0 to 30 g of CaPFA/kg of DM, respectively). The number of medium-sized
      follicles, and diameters of the ovulatory follicles and corpora lutea, were not
      affected by CaPFA supplementation. It is concluded that dietary total fat
      concentration should be below 50 g/kg of DM to avoid depressing plasma insulin
      concentration in cows at the start of the breeding period.

PMID- 18832205
TI  - Detection of mastitis pathogens by analysis of volatile bacterial metabolites.
AB  - The ability to detect mastitis pathogens based on their volatile metabolites was
      studied. Milk samples from cows with clinical mastitis, caused by Staphylococcus
      aureus, coagulase-negative staphylococci, Streptococcus uberis, Streptococcus
      dysgalactiae, and Escherichia coli were collected. In addition, samples from cows
      without clinical mastitis and with low somatic cell count (SCC) were collected
      for comparison. All mastitis samples were examined by using classical
      microbiological methods, followed by headspace analysis for volatile metabolites.
      Milk from culture-negative samples contained a lower number and amount of
      volatile components compared with cows with clinical mastitis. Because of
      variability between samples within a group, comparisons between pathogens were
      not sufficient for classification of the samples by univariate statistics.
      Therefore, an artificial neural network was trained to classify the pathogen in
      the milk samples based on the bacterial metabolites. The trained network
      differentiated milk from uninfected and infected quarters very well. When
      comparing pathogens, Staph. aureus produced a very different pattern of volatile
      metabolites compared with the other samples. Samples with coagulase-negative
      staphylococci and E. coli had enough dissimilarity with the other pathogens,
      making it possible to separate these 2 pathogens from each other and from the
      other samples. The 2 streptococcus species did not show significant differences
      between each other but could be identified as a different group from the other
      pathogens. Five groups can thus be identified based on the volatile bacterial
      metabolites: Staph. aureus, coagulase-negative staphylococci, streptococci
      (Strep. uberis and Strep. dysgalactiae as one group), E. coli, and uninfected
      quarters.

PMID- 18832206
TI  - Passive immunity in Ontario dairy calves and investigation of its association
      with calf management practices.
AB  - Adequate passive transfer of maternal immunoglobulin is important for optimal
      health and performance in newborn dairy calves. From June to October 2003 and
      January to April 2004, blood samples were collected from 961 dairy calves 0 to 8
      d of age on 11 farms in southwestern Ontario. This was followed by a second study
      conducted from May to October 2004, in which similar samples were taken from 422
      calves up to 8 d of age on 119 dairy farms throughout southern Ontario. For each
      sample collected, serum refractometry was used to evaluate serum total protein
      (TP) as a measure of passive transfer of maternal immunity. During each study,
      producers were asked to provide information on calf management practices,
      including details of colostrum feeding. Data were analyzed to assess the levels
      of maternal immunity present in the calves, and to investigate whether these were
      associated with any calf management or colostrum feeding practices used on the
      farms. Serum TP readings ranged from 3.5 to 9.8 g/dL. Controlling for any effects
      of variation between farms, we found no statistically significant difference in
      serum TP levels, or risk of failure of passive transfer (FPT), between heifer and
      bull calves. The odds of FPT in calves on farms where more than 75% of cows were
      usually allowed to remain with their calves for more than 3 h after calving were
      significantly higher than the odds of FPT in calves on farms where dams and
      calves were separated within 3 h of the birth. Furthermore, an increased volume
      of colostrum given to calves within 6 h of birth was significantly associated
      with a reduced risk of FPT in calves. Information from this work provides
      valuable insight into the efficiency of passive transfer in newborn dairy calves
      in southern Ontario.

PMID- 18832207
TI  - Uptake and utilization of trans octadecenoic acids in lactating dairy cows.
AB  - Trans fatty acids (FA) arise in ruminant-derived foods as a consequence of rumen
      biohydrogenation and are of interest because of their biological effects and
      potential role in chronic human diseases. Our objective was to compare 2 trans
      FA, elaidic acid (EA; trans-9 18:1) and vaccenic acid (VA; trans-11 18:1), with
      oleic acid (OA; cis-9 18:1) relative to plasma lipid transport and mammary
      utilization for milk fat synthesis. Three ruminally cannulated, Holstein dairy
      cows, 259 +/- 6 DIM (mean +/- SEM), were randomly assigned in a 3 x 3 Latin
      square design. Treatments were a 4-d abomasal infusion of 1) OA (45.5 g/d), 2) EA
      (41.7 g/d), and 3) VA (41.4 g/d). Milk samples were collected at each milking and
      blood samples were collected at the start and end of each treatment period. The
      proportions of total plasma FA associated with each plasma lipid fraction at
      baseline (pretreatment) were 62.6 +/- 0.6% phospholipids, 26.1 +/- 0.6%
      cholesterol esters, 9.8 +/- 0.4% triglycerides, and 1.5 +/- 0.1% nonesterified
      fatty acids; these values were unaffected by treatment. There were striking
      differences in the FA composition of the individual plasma lipid fractions and in
      the distribution of specific 18-carbon FA among the lipid fractions. Infusion of
      treatment isomers caused their specific increase in the various plasma lipid
      fractions but had no effect on milk production variables, including milk fat
      yield and content. Transfer efficiency of infused OA, EA, and VA to milk fat
      averaged 65.5 +/- 3.0%, 59.7 +/- 1.5%, and 54.3 +/- 0.6%, respectively. For the
      VA infusion, 24.6 +/- 1.1% of the transfer was accounted for by the increased
      yield of cis-9, trans-11 conjugated linoleic acid in milk fat, consistent with
      its endogenous synthesis from VA via the mammary enzyme Delta(9)-desaturase.
      Notably, linoleic acid (18:2n-6) and linolenic acid (18:3n-3) accounted for 47.7%
      of total plasma FA, but only 2.6% of FA in milk. Overall, results demonstrate
      clear differences in plasma transport and mammary uptake and utilization of 18
      carbon FA, and these relate to the location, orientation, and number of double
      bonds.

PMID- 18832208
TI  - Relationships between the concentration of insulin-like growth factor-1 in serum
      in dairy cows in early lactation and reproductive performance and milk yield.
AB  - The objective of this study was to evaluate the relationships of different
      insulin-like growth factor-1 (IGF1) measures [5 distinct IGF1 concentrations on
      particular days, area under the curve (AUC), and linear regression coefficient]
      in the postpartum period in lactating dairy cows and reproductive performance. A
      total of 417 healthy multiparous Holstein-Friesian cows were enrolled in the
      study. Serum samples for the determination of the concentration of IGF1 were
      collected on d 0, 4, 10, 20, and 40 postpartum (pp). The concentration of total
      IGF1 in serum was determined by immunometric chemiluminescence immunoassay. All
      cows were examined for vaginal discharge as a sign of clinical endometritis at 20
      d pp by external inspection and rectal palpation. The mean concentration of IGF1
      ranged from 57 +/- 18.9 ng/mL within the first 12 h pp to 74 +/- 19.9 ng/mL at 40
      d pp. On d 10 pp, first and all artificial insemination conception rates were
      greater in cows with IGF1 concentrations above the median compared with cows with
      IGF1 concentrations below the median. Cows with greater AUC (second to fourth
      quartile) conceived earlier (11.4, 16.0, and 18.8 d) than cows in the first IGF1
      quartile (117.0 +/- 43.6). Proportion of cows pregnant within 200 d pp increased
      significantly from the first to the third IGF1 quartile of AUC (58.7, 66.7, and
      74.0%). The proportion of cows culled decreased from the first to the fourth IGF1
      quartile. Correlations between IGF1 measures and days to pregnancy were
      significant (except for the linear regression coefficients) but low (R(2) =
      0.0009 to 0.025). Differences between single or composite measurements of IGF1
      were not significant. We could also demonstrate a statistically significant
      correlation between the concentration of IGF1 in serum and the average 10-d milk
      production (31.6 to 44.0 kg). In conclusion, our study indicates that single or
      multiple measurements of IGF1 concentration in the postpartum period have very
      limited value to predict individual fertility in dairy cows.

PMID- 18832209
TI  - Milk production change following clinical mastitis and reproductive performance
      compared among J5 vaccinated and control dairy cattle.
AB  - Naturally occurring cases of bovine clinical mastitis (CM) were studied among J5
      vaccinates and controls on 3 commercial dairy farms. Milk production change and
      reproductive performance following CM were compared between the 2 groups. Among
      306 controls and 251 vaccinates, there were 221 new cases of CM affecting 120
      cows; 437 lactations never had a case of CM. Environmental pathogens made up 90%
      (159/176) of etiologic agents isolated. Change in daily milk production following
      CM was associated with J5 vaccination, days in milk (DIM) at onset of CM, and
      herd effect as well as each 2-way interaction between the 3 factors. The adjusted
      daily milk for 21 d following CM was 7.6 kg greater among J5 vaccinates than
      controls; however, this protective effect of vaccination waned with increasing
      DIM at onset of CM. A mixed linear model with autoregressive order 1 [AR(1)]
      correlation structure estimated the daily milk production of any cow (whether or
      not she had CM) on a given DIM. Cows with CM caused by nonagalactiae
      streptococci, Staphylococcus aureus, Escherichia coli, or Klebsiella lost
      significant daily milk production for the entire lactation relative to
      nonmastitic cows. Another mixed linear model for only coliform CM cases (E. coli,
      Klebsiella, and Enterobacter) within the first 50 DIM showed milk loss for 21 d
      following coliform CM to be significantly less for J5 vaccinates than for
      controls, by 6 to 15 kg per day. Cows were significantly less likely to become
      pregnant if they had CM caused by E. coli (42% pregnant) or Streptococcus spp.
      (38% pregnant), whereas 78% (342/437) of cows with no mastitis conceived. Days
      open (number of days from calving until pregnancy) averaged 131 d for cows with
      no CM and 162 d for cows that had at least one case of CM. Days until conception,
      days until last breeding, days open, times bred, and percentage of cows pregnant
      by 200 DIM were not changed with J5 vaccination. Nonetheless, an important
      benefit of the use of J5 bacterin appears to be reduction of the loss of daily
      milk production following CM, whether all cases or only those caused by coliform
      bacteria were considered.

PMID- 18832210
TI  - Impact of intake water temperatures on reticular temperatures of lactating dairy
      cows.
AB  - Automatic temperature recording may allow early detection of disease, estrus,
      heat stress, and the onset of calving. The phase IV Cattle Temperature Monitoring
      System (MaGiiX Inc., Post Falls, ID) utilizes a passive bolus equipped with a
      temperature sensor, a stationary panel reader to query the bolus, and software to
      collect, analyze, and display data. One potential limitation to collection of
      reticular temperatures is the effect of water temperature and consumption on
      recorded temperatures. Two replicated 3 x 3 Latin square experiments were
      conducted at the Purdue Dairy Research and Education Center to assess the impact
      of water intake on reticular temperatures using the Cattle Temperature Monitoring
      System. Nine high-producing, mid-lactation, second-parity cows with low somatic
      cell counts were selected. Before administering a water treatment, access to feed
      and water was restricted for at least 2 h. Baseline reticular temperatures were
      established from measurements before water intake. In experiment 1, treatments
      were 25.2 kg of hot water (34.3 degrees C +/- 1.0), warm water (18.2 degrees C +/
      0.4), or cold water (7.6 degrees C +/- 0.4). In experiment 2, treatments were
      18.9 kg of body-temperature water (38.9 degrees C +/- 0.2), cold water (5.1
      degrees C +/- 0.4), or control (no water). Following water intake, reticular
      temperatures were collected for 3 h. In experiment 1, an initial dramatic
      decrease in reticular temperature was observed followed by a gradual increase
      toward baseline. Least squares means for maximum drop in temperature were 8.5 +/-
      0.5, 6.9 +/- 0.5, and 2.2 +/- 0.5 degrees C for cold, warm, and hot water
      treatments, respectively. Yet at 3 h, reticular temperatures did not return to
      the baseline. In experiment 2, control cows remained within the baseline
      confidence interval through the observation period, and cows receiving body
      temperature water experienced an initial decrease in temperature (0.4 +/- 0.2
      degrees C) with a return to within the baseline confidence interval within 15
      min. Cows receiving cold water did not return to within the baseline confidence
      interval after a large decrease of 9.2 +/- 0.2 degrees C during the 3-h
      observational period. Moreover, a regression analysis of continued ascent in
      temperatures predicted that temperatures would return to baseline within 3.5 h.
      These results demonstrate that, when cows consume large quantities of cold water,
      the effect of water intake is sizable and sustained. The value of reticular
      temperatures for daily monitoring in a production setting hinges largely on the
      implications of this impact.

PMID- 18832211
TI  - Herd- and cow-level prevalence of foot lesions in Ontario dairy cattle.
AB  - The objectives of this cross-sectional study were to determine herd-level and cow
      level prevalence estimates for 11 foot lesions in Ontario dairy cattle. Foot
      lesions were recorded by 5 hoof trimmers on 13,530 cows in 204 Ontario dairy
      herds from March 2004 to May 2005. Significant differences existed between free
      stall and tie-stall housing. In free-stall housing systems, 46.4% of cows had a
      foot lesion, compared with 25.7% of cows in tie-stall barns. Digital dermatitis
      was the most common lesion in tie stalls, occurring in 9.3% of cows and 69.7% of
      the herds, whereas in free-stall herds, 22.7% of cows and 96.7% of the herds were
      affected. The most common hoof horn lesions were hemorrhages and ulcers, at 7.7
      and 4.7% in tie-stall housing and 11.0 and 9.2% in free-stall housing,
      respectively. Foot blocks were used to treat 2.2% of cows in free stalls and 0.3%
      in tie stalls. Intraclass correlation coefficients ranged from 9.5 to 17.3 for
      hoof horn lesions and 28.0 to 38.7 for infectious lesions. In summary, foot
      lesions diagnosed at the time of hoof trimming are common in Ontario, and
      appropriate treatment for hoof horn lesions is low.

PMID- 18832212
TI  - Energy balance and reproduction on dairy cows fed to achieve low or high milk
      production on a pasture-based system.
AB  - This study investigated the energy balance, metabolic changes, reproduction, and
      health in Australian Holstein-Friesian cows of average genetic merit fed to
      produce 6,000 L of milk/cow per lactation (restricted production; Rp) on a
      predominantly grazed pasture diet, or 9,000 L of milk/cow per lactation (high
      production: Hp) on a more intensive feeding regimen by using a partial mixed
      ration to supplement pasture. The mean 4% fat-corrected milk (FCM) and standard
      deviation achieved was 8,466 +/- 1,162 L/cow per lactation for the Hp herd and
      6,748 +/- 787 L/cow per lactation for the Rp herd. During early lactation, the
      degree of estimated negative energy balance was less in the Hp cows than in the
      Rp cows (-16.1 vs. -29.1 MJ/cow per day, respectively). Consequently, the
      mobilization of body reserves was also lower in the Hp cows, and this was
      reflected in lower concentrations of nonesterified fatty acids (0.70 vs. 0.84
      mmol/L) and beta-hydroxybutyrate (0.51 vs. 0.69 mmol/L) and greater
      concentrations of glucose (3.51 vs. 3.34 mmol/L) and insulin-like growth factor-I
      (78.9 vs. 58.7 ng/mL) for Hp and Rp cows, respectively. After calving, body
      condition score and body weight decreased to a similar extent in both herds and
      did not reflect the differences in mobilization of body reserves between the 2
      herds. Reproductive performance was not significantly related to level of milk
      yield. The mean interval from calving to first active corpus luteum was 33 (SD =
      20) d postpartum, and there were 1.4 (SD = 0.8) estrus cycles before the
      beginning of the breeding period (>50 d postpartum). The interval from calving to
      pregnancy was 114 d, and the pregnancy rate after 12 wk of mating was 74%. The
      number of cows with ovarian abnormalities was also similar between the 2 herds.
      Cows with a long postpartum anestrus had the lowest concentration of insulin-like
      growth factor-I. The number of health-related disorders was also similar between
      the herds, with the exception of mastitis, for which the incidence was
      significantly greater in the Hp cows. The results indicate that the production
      per cow could be increased from 6,748 L of FCM/cow per lactation for cows grazing
      pasture and supplemented with concentrates only at milking to 8,466 L of FCM/ cow
      per lactation, in one lactation, by supplementing pasture with a partial mixed
      ration. Despite the fact that production per cow increased substantially, the
      degree of estimated negative energy balance and the metabolic changes in early
      lactation were lower and reproductive performance was maintained.

PMID- 18832213
TI  - Cleanliness scores as indicator of Klebsiella exposure in dairy cows.
AB  - This study was designed to explore the relationship between cow and udder
      cleanliness scores and the risk of isolation of Klebsiella spp. from lower hind
      legs and teat ends, respectively. The distribution of Klebsiella species was
      compared among isolates from teat ends, legs, and cases of clinical mastitis
      obtained from 2 dairy farms in New York State, with 850 and 1,000 cows,
      respectively. Farms were visited twice approximately 4 wk apart in August and
      September 2007 to obtain cleanliness scores and swabs from legs and teats.
      Isolates of Klebsiella clinical mastitis from each farm were collected from July
      through October 2007. Two studies were conducted. In the first study, whole-cow
      cleanliness of a purposive sample of 200 lactating cows was scored using a 4
      point scale, and swabs were taken from their lower hind legs. In the second
      study, udder cleanliness of a separate convenience sample of 199 lactating cows
      was scored in the milking parlor, and swabs were taken from their teat ends
      before and after premilking udder preparation. Prevalence of Klebsiella spp. on
      legs and teat ends before udder preparation was 59 and 60%, respectively.
      Logistic regression was used to explore the association between isolation of
      Klebsiella spp. and cleanliness scores. Cow cleanliness scores and udder
      cleanliness scores were not associated with detection of Klebsiella on legs and
      on teats before udder preparation, respectively. After udder preparation, 43% of
      previously Klebsiella positive teat end samples remained positive, with
      significant differences between farms and months. Teats from dirty udders were
      significantly more likely to test positive for Klebsiella after udder preparation
      than teats from clean udders. The proportion of Klebsiella pneumoniae and
      Klebsiella oxytoca isolates was similar for isolates from teat end swabs and
      clinical mastitis cases, supporting the notion that the presence of Klebsiella on
      teat ends may lead to opportunistic intramammary infections. Udder cleanliness
      scores could be used as a management tool to monitor the risk of exposure to
      Klebsiella spp. on teat ends.

PMID- 18832214
TI  - Short communication: antibiotic residues in milk following the use of
      intravaginal sponges for estrus synchronization in dairy ewes.
AB  - The addition of antibiotics to intravaginal sponges used to synchronize ewe
      estrus is currently a recommended practice for the prevention of posttreatment
      vaginal infections. Application of this antibiotic treatment is usually done
      without withdrawal periods for milk, but official pharmaceutical instructions do
      not consider the extra-label use of antibiotics, which could result in the
      presence of antibiotic residues in milk. To understand the effects of the use of
      antibiotics on the performance of these hormonal treatments, milk collected from
      a group of Manchega ewes estrus synchronized by intravaginally inserted
      progestagen sponges jointly impregnated with antibiotics (benzyl penicillin
      procaine: 1,000,000 IU/25 sponges plus DH-streptomycin: 1 g/25 sponges) was
      evaluated for antibiotic residue persistence with 5 types of antibiotic screening
      tests (BRT, Copan CMT, Delvotest MSC, Eclipse 100, and New SNAP Beta-Lactams).
      Time to antibiotic residue depletion was established by a logistic regression
      model, and a significant response to milking order was observed in all methods.
      Positive or doubtful tests were observed after the insertion of intravaginal
      sponges for all assay screening tests at the time of the first milking and
      sometimes afterwards.

PMID- 18832215
TI  - Short communication: dominance in free-stall-housed dairy cattle is dependent
      upon resource.
AB  - The main objective was to assess the consistency in competitive success across 3
      common resources available to dairy cows housed in free-stall barns.
      Specifically, we determined if those cows that displaced other cows most often at
      the feed bunk (high-ranking) had priority of access to free-stalls or a
      mechanical brush. Our secondary objective was to determine if the displacements
      at each resource were a function of usage of that resource. These objectives were
      tested using 6 groups of 12 lactating dairy cows housed in pens with 0.6 m of
      bunk space per cow, 1 free-stall per cow, and 1 mechanical brush per pen. Time
      lapse video was used to quantify the time spent feeding, in the stalls, and using
      the mechanical brush. The incidence of displacements at the feed alley and lying
      area was measured for 3 d consecutively. Usage was lower for the brush, so
      displacements were monitored for 14 d consecutively. The individual measures of
      competitive success were not highly correlated between resources indicating a cow
      that frequently displaced other cows for access to one particular resource did
      not always do so when accessing the other resources. Competition at the feeder
      was responsible for 87.6 +/- 1.4% of displacements observed throughout the
      experiment, indicating that gaining access to feed was a high priority for cows.
      These results suggest that competitive success by dairy cows may vary according
      to each cow's motivation to access the resource.

PMID- 18832216
TI  - Short communication: effect of alley floor cleanliness on free-stall and udder
      hygiene.
AB  - The objective was to evaluate the effect of alley floor cleanliness on the
      hygiene of the free-stalls and udder and teats of cows. Mechanical scrapers were
      used on rubber-slatted floors to improve the cleanliness of the alley floor. Two
      sections containing 21 cows each were evaluated once weekly for a period of 3 wk.
      One section had scrapers on the rubber-slatted floor in the alleys and the other
      section did not. The scrapers ran 12 and 7 times/d in the free-stall alley and
      feed alley, respectively. Manure accumulation in the alleys at approximately 2 h
      after the scrapers had run was less in the section with the scraper than in that
      without the scraper. Differences between sections with and without scrapers were
      found in the sites close to the wall in the feed alley, and immediately behind
      the free-stalls in the free-stall alley. In the section without scrapers, manure
      accumulation was greater in the free-stall alley than in the feed alley. Manure
      contamination of the area in the free-stalls where the udder normally comes in
      contact with the free-stall floor was significantly reduced from 29.1 to 17.9 +/-
      2.4 g of dry matter when the alley floor was kept clean by the use of scrapers.
      The hygiene scores of the dirtiness of udders were reduced from 25.8 +/- 1.7 to
      18.9 +/- 1.6, and those of the teats from 37.9 +/- 2.3 to 24.2 +/- 2.3 in the
      section with scrapers and cleaner alley floor compared with the section without
      scrapers. The scrapers greatly improved the hygiene on the rubber-slatted alley
      floor. The cleaner alley floor had a positive effect on the cleanliness of the
      free-stalls and the udder and teats of the cows.

PMID- 18832217
TI  - Effects of substitution of different levels of steam-flaked corn for finely
      ground corn on lactation and digestion in early lactation dairy cows.
AB  - Eight multiparous Holstein cows, 4 of them fitted with rumen cannulas, were used
      to test the effects of substitution of steam-flaked corn (SFC) for equal amounts
      of finely ground corn (FGC) in diets on feed intake and digestion, blood
      metabolites, and lactation performance in early lactation dairy cows. Cows were
      fed 4 diets in a replicated 4 x 4 Latin square design. The fistulated cows formed
      1 replicate. Each experimental period lasted for 3 wk. The 4 diets contained 0,
      10, 20, or 40% SFC and 40, 30, 20, or 0% FGC (dry matter basis), respectively.
      The milk protein content and yield, milk solid nonfat content and yield, plasma
      glucose concentration, and dry matter intake increased as the proportion of SFC
      increased in diets. Apparent total tract digestibilities of dry matter, organic
      matter, neutral detergent fiber, acid detergent fiber, and average ruminal fluid
      NH(3)-N concentration decreased with increasing levels of SFC. The ruminal fluid
      pH was not affected by the substitution of SFC for FGC. The 20% SFC substitution
      improved digestion of crude protein, yield of fat-corrected milk, milk lactose
      content, fat, and fat yield. The 40% SFC substitution increased urea
      concentration in both plasma and milk. It was concluded that 20% of SFC
      substitution for FGC appeared to be an appropriate level in diet for early
      lactation dairy cows.

PMID- 18832218
TI  - Ruminal phosphorus disappearance from corn and soybean feedstuffs.
AB  - Byproducts of corn and soybeans have high phosphorus (P) content, but little is
      known about their P disappearance in the rumen of lactating dairy cows. In situ
      disappearance of P from corn and soybean feed-stuffs was determined in 2
      experiments. In the first experiment, 3 ruminally cannulated lactating dairy cows
      were used to estimate in situ P disappearance of 9 feed ingredients that included
      3 sources of dried distillers grains with solubles (DDG; DGa, DGb, DGc), corn,
      corn germ, solvent-extracted soybean meal, (44% CP; SBM), expeller soybean meal
      (SoyPlus; SP), extruded soybeans (ES), and soyhulls (SH). Nylon bags were
      incubated in the rumen of each cow for 2, 6, 12, 18, 24, 36, and 48 h. The water
      soluble fraction of P (A(P)) was greatest in DDG (mean 82.1%) followed by corn
      germ (77%), with SH having the least A(P) among all feedstuffs (45%). The
      remaining feedstuffs (SBM, SP, ES, and corn) were similar in A(P) (64.2%). The
      slowly available fraction of P (B(P)) was greatest in SH (45.6%), lowest in DDG
      (13.5%), and intermediate, averaging 31.4%, in SBM, ES, SP, and corn. The
      effective disappearance of P (ED(P)) was greatest for DDG (93.5%), whereas corn
      germ, ES, SBM, and SP followed with an ED(P) of 93.3, 88.0, 87.5, and 87.0%,
      respectively. The ED(P) was less for corn and SH than for the other feedstuffs at
      83.3 and 69.1%, respectively. Rate of P disappearance was similar for all
      feedstuffs (16.2%/h). In the second experiment, 3 new sources of DDG (DG1, DG2,
      and DG3), and one wet distillers grains with solubles (WDG) source were incubated
      for 3, 6, 12, 24, and 36 h on replicate days in the rumen of 2 cannulated
      lactating dairy cows. Fraction A(P) varied from 82.7 to 90.3%, with that in WDG
      being the least soluble. The WDG source had a greater B(P) fraction (15.8%)
      compared with the DDG sources (9.5%). The WDG had the lowest ED(P) (88.1%),
      whereas the DDG varied from 89.7 to 92.7%. Corn and soybean byproducts tested,
      with the exception of SH, have high ruminal P disappearance as measured with the
      Dacron bag technique.

PMID- 18832219
TI  - The relative merit of ruminal undegradable protein from soybean meal or soluble
      fiber from beet pulp to improve nitrogen utilization in dairy cows.
AB  - Early lactating dairy cows were used to determine whether the replacement of
      solvent-extracted soybean meal [SSBM; a source of rumen-degradable protein (RDP)]
      with expeller soybean meal (ESBM; a source of rumen-undegradable protein), or the
      replacement of high-moisture shelled corn (HMSC) with beet pulp (a source of
      soluble fiber) would be effective in improving efficiency of N usage for milk
      production. The study was designed as a replicated 4 x 4 Latin square with 21-d
      periods. Eight multiparous Holstein cows were fed, ad libitum, the following
      diets, which were based on alfalfa silage and HMSC, and formulated to be
      isocaloric: 1) basal diet without a protein supplement (negative control diet:
      NC); 2) NC supplemented with solvent-extracted SBM (diet SSBM); 3) NC
      supplemented with expeller SBM (diet ESBM); 4) SSBM in which unmolassed dried
      beet pulp replaced half of the HMSC (diet SSBMBP). Compared with diet NC, protein
      supplementation increased intake of organic matter and dry matter. Milk and milk
      protein yields were lower with NC but this diet resulted in the greatest
      efficiency of N usage for milk production (30% milk N/N intake). Supplementation
      with ESBM, a proven source of RUP, increased plasma concentrations of histidine
      and branched-chain amino acids, and reduced milk urea N concentration, but failed
      to improve the yields of milk or milk protein. Milk fat yield tended to decrease
      with RUP supplementation. Replacing part of HMSC with soluble fiber from beet
      pulp (SSBMBP) tended to decrease milk production compared with SSBM; the effect
      was due to a reduction in dry matter intake. There were no differences among
      diets SSBM, ESBM, or SSBMBP in urinary excretion of purine derivatives. Neither
      substitution of ESBM for SSBM nor partial replacement of HMSC with beet pulp
      altered the efficiency of N usage for milk production or manure N excretion.

PMID- 18832220
TI  - Repeated ruminal acidosis challenges in lactating dairy cows at high and low risk
      for developing acidosis: feed sorting.
AB  - An experiment was conducted to determine whether the susceptibility of cows to
      ruminal acidosis influences feed sorting and whether feed sorting changes during
      a bout of ruminal acidosis. Eight ruminally cannulated cows were assigned to 1 of
      2 acidosis risk levels: low risk (LR, mid-lactation cows fed a 60% forage diet)
      or high risk (HR, early lactation cows fed a 45% forage diet). As a result, diets
      were intentionally confounded with milk production to represent 2 different
      acidosis risk scenarios. Cows were exposed to an acidosis challenge in each of
      two 14-d periods. Each period consisted of 3 baseline days, a feed restriction
      day (restricting TMR to 50% of ad libitum intake), an acidosis challenge day (1-h
      meal of 4 kg of ground barley/wheat before allocating the TMR), and a recovery
      phase. Ruminal pH was measured continuously for the first 9 d of each period
      using an indwelling system. Feed and orts were sampled for 2 baseline days, on
      the challenge day, and 1 and 3 d after the challenge day for each cow and
      subjected to particle size analysis. The separator contained 3 screens (18, 9,
      and 1.18 mm) and a bottom pan to determine the proportion of long, medium, short,
      and fine particles, respectively. Sorting was calculated as the actual intake of
      each particle size fraction expressed as a percentage of the predicted intake of
      that fraction. All cows sorted against the longest and finest TMR particles and
      sorted for medium-length particles. Sorting was performed to a greater extent by
      the HR cows, and this sorting was related to low ruminal pH. Both HR and LR cows
      altered their sorting behavior in response to acidosis challenges. For the HR
      cows, severe acidosis was associated with increased sorting for the longer
      particles in the diet and against the shorter particles, likely to lessen the
      effects of the very.

PMID- 18832221
TI  - Alfalfa cut at sundown and harvested as baleage improves milk yield of late
      lactation dairy cows.
AB  - Alfalfa (Medicago sativa L.) cut at sundown has been shown to contain greater
      concentration of total nonstructural carbohydrates (TNC) than that cut at sunup.
      Fourteen multiparous (8 ruminally cannulated) and 2 primiparous lactating dairy
      cows were randomly assigned to 2 treatments in a crossover design (2 periods of
      24 d) to investigate the effects of alfalfa daytime cutting management on ruminal
      metabolism, nutrient digestibility, N balance, and milk yield. Half of each
      alfalfa field (total of 3 fields) was cut at sundown (PM) after a sunny day,
      whereas the second half was cut at sunup (AM) on the following day. Both PM and
      AM cuts were field-wilted and harvested as baleage (531 +/- 15.0 g of dry
      matter/kg of fresh matter). Bales (PM and AM) were ranked according to their
      concentrations of TNC, paired, and each pair of PM and AM baleages was then
      assigned to each experimental day (total of 48 d). The difference in TNC
      concentration between PM and AM baleages fed during the 10 d of data and sample
      collection varied from -10 to 50 g/kg of dry matter. Each pair of baleage was fed
      ad libitum to cows once daily with no concentrate. Ruminal molar proportion of
      acetate and total volatile fatty acid concentration were greater in animals fed
      the AM baleage, whereas the proportion of valerate was greater with PM baleage;
      no other significant changes in ruminal molar proportions of volatile fatty acids
      were observed between forage treatments. Digestible organic matter intake,
      organic matter digestibility, and plasma Lys concentration were significantly
      greater in cows fed PM alfalfa, suggesting that more nutrients were available for
      milk synthesis. Significantly lower body weight gain and retained N as a
      proportion of N intake were observed in cows fed PM alfalfa, thus suggesting that
      nutrients were channeled to milk synthesis rather than to body reserves. Intake
      of dry matter (+1.0 kg/d), and yields of milk (+1.0 kg/d), milk fat (+70 g/d),
      and milk protein (+40 g/d) were significantly greater in cows fed PM vs. AM
      alfalfa. Concentration of milk urea N and excretion of urea N as a proportion of
      total urinary N were significantly reduced, and milk N efficiency was increased
      when feeding PM vs. AM alfalfa, indicating an improvement in N utilization.
      Increasing the TNC concentration of alfalfa by shifting forage cutting from sunup
      to sundown improved N utilization and milk production in late-lactation dairy
      cows.

PMID- 18832222
TI  - An observational study on early-lactation metabolic profiles in Swedish
      organically and conventionally managed dairy cows.
AB  - The aim of this observational study was to compare indicators of energy balance
      in early lactation in organically managed dairy cows (OMC) and conventionally
      managed dairy cows (CMC) under field conditions. The diets of OMC and CMC differ
      as a consequence of the rules and principles of organic dairy farming. The study
      was based on clinical examinations and blood samples from cows within the range
      from 2 wk prepartum to 6 wk postpartum, collected from 20 organic and 20
      conventional dairy farms with 3 visits at each farm. The farms were located in a
      southeastern area of Sweden and ranged in size from 45 to 120 cows. The blood
      parameters selected to reflect energy metabolism were nonesterified fatty acids,
      beta-hydroxybutyrate, glucose, and insulin. At clinical examination body
      condition score was registered. The shape of the lactation curve in early
      lactation was modeled to assess potential differences that could explain the
      blood parameter profiles. The conventionally managed cows increased their milk
      yield faster than OMC within the first 2 wk of lactation. Blood nonesterified
      fatty acid concentrations were similar between the management types, but with a
      tendency of lesser concentrations in OMC, primarily in early lactation.
      Postcalving beta-hydroxybutyrate concentrations were constantly lesser in OMC
      during the first 6 wk of lactation. An interaction between season and insulin
      concentration necessitated stratification on season. During spring the profiles
      overlapped, but there was a significant difference in the first 4 d post-calving,
      when organically managed cows had greater insulin concentrations and in d 30 to
      34 when conventionally managed cows had greater insulin concentrations. During
      fall the profiles overlapped completely and there was no significant difference
      at any point in time. Glucose concentrations tended to decrease slightly
      postcalving followed by a gradual elevation to a concentration just under the
      precalving concentration during the study period. Body condition scores decreased
      slightly over the study period. No differences were found between the management
      types with regard to glucose concentrations or registered body condition score.
      In conclusion, the OMC did not show a greater extent of mobilization of body
      tissue than CMC as expressed by our study variables. Hence, OMC adjusted the
      production amount according to feed intake.

PMID- 18832223
TI  - Short communication: malic acid does not promote vaccenic acid accumulation in
      mixed ruminal fluid with fractionated fish oil by a rumen-simulation technique.
AB  - The objective of this study was to determine whether malic acid could promote the
      accumulation of vaccenic acid in the rumen. The control diet was composed of a
      65:35 ratio of forage to concentrate with 1% (dry matter basis) added
      fractionated fish oil (rich in docosahexaenoic acid), and treatment diets
      consisted of the control diet with added malic acid to achieve final
      concentrations of 10 mM (treatment 1) and 20 mM (treatment 2), respectively. The
      experiment was conducted with rumen-simulation equipment (Rusitec) consisting of
      9 fermenters. Each treatment included 3 fermenters as replicates. After 7 d of
      incubation, concentrations of vaccenic acid from treatment 1 (4.38% fatty acids)
      and treatment 2 (4.46% fatty acids) were similar to that of the control treatment
      (4.51% fatty acids). The disappearance of docosahexaenoic acid was not different
      among the control, treatment 1, or treatment 2. These data indicated that malic
      acid did not promote the accumulation of vaccenic acid in ruminal fluid.

PMID- 18832224
TI  - Short communication: the effects of histidine-supplemented drinking water on the
      performance of lactating dairy cows.
AB  - An experiment was conducted to test the hypothesis that a sufficient proportion
      of histidine (His) included in the drinking water of lactating cows bypasses the
      rumen to have an effect on milk synthesis. Eight dairy cows (45 +/- 15 d in milk)
      were given either 0 or 2.5 g/L of His in the drinking water in a crossover design
      of two 7-d periods. Cows were offered a corn and alfalfa silage-based total mixed
      ration for ad libitum intake. Water was provided ad libitum to each cow in an
      individual automatic drinking vessel with a flow meter attached. Water intake
      tended to increase from 85.1 to 92.1 L/d when His was added. Concentrations of
      His in plasma samples collected on the last day of each period tended to increase
      from 14.6 to 21.6 muM, corresponding to an estimated 0.4% bypass of the imbibed
      histidine. Other amino acid concentrations in plasma were not affected by His
      supplementation. Milk yield increased by 1.7 L/d with His treatment, lactose
      yield increased by 90 g/d, and there were tendencies for protein yield to
      increase, fat percentage to decrease, and protein to fat ratio to increase. An
      improvement in postruminal histidine flow can influence milk production and
      composition but the proportion of imbibed water that bypasses the rumen will have
      to be increased to take advantage of drinking water as a vehicle to transfer His
      postruminally.

PMID- 18832225
TI  - Short communication: effects of 2-hydroxy-4-(methylthio) butanoic acid isopropyl
      ester on milk production and composition of lactating Holstein dairy cows.
AB  - Sixteen multiparous Holstein cows were used to determine the effects of 2-hydroxy
      4-(methylthio) butanoic acid isopropyl ester (HMBi: 0 vs. 1.26 g/kg of total
      ration dry matter (DM) and dietary crude protein (CP) concentration [14.7% (low)
      vs. 16.9% (standard), DM basis] on milk yield and composition using a replicated
      4 x 4 Latin square design experiment with 4-wk periods. Cows were fed ad libitum
      a total mixed ration with a 1:1 forage-to-concentrate ratio (DM basis), and diets
      provided an estimated 6.71 and 1.86% lysine and methionine, respectively, in
      metabolizable protein for the low-protein diet and 6.74 and 1.82% in the standard
      protein diet. Dry matter intake, milk yield, and composition were measured during
      wk 4 of each period. There were no effects on DM intake, which averaged 24.7
      kg/d. There was an interaction between dietary CP and HMBi for milk yield and
      3.5% fat-corrected milk (FCM). Feeding HMBi decreased milk and FCM yield when fed
      with the low-CP diet but did not affect milk or FCM yield when fed with the
      standard CP diet. Feeding HMBi increased milk protein concentration regardless of
      diet CP concentration and increased milk protein yield when added to the standard
      CP diet but not the low-CP diet. The positive effect of HMBi on milk protein
      yield was only observed at the standard level of dietary CP, suggesting other
      factors limited the response to HMBi when dietary protein supply was restricted.

PMID- 18832226
TI  - Genetic relationship between culling, milk production, fertility, and health
      traits in Norwegian red cows.
AB  - First-lactation records on 836,452 daughters of 3,064 Norwegian Red sires were
      used to examine associations between culling in first lactation and 305-d protein
      yield, susceptibility to clinical mastitis, lactation mean somatic cell score
      (SCS), nonreturn rate within 56 d in heifers and primiparous cows, and interval
      from calving to first insemination. A Bayesian multivariate threshold-linear
      model was used for analysis. Posterior mean of heritability of liability to
      culling of primiparous cows was 0.04. The posterior means of the genetic
      correlations between culling and the other traits were -0.41 to 305-d protein
      yield, 0.20 to lactation mean SCS, 0.36 to clinical mastitis, 0.15 to interval
      from calving to first insemination, -0.11 to 56-d nonreturn as heifer, and -0.04
      to 56-d nonreturn as primiparous cow. As much as 66% of the genetic variation in
      culling was explained by genetic variation in protein yield, clinical mastitis,
      interval of calving to first insemination, and 56-d nonreturn in heifers, whereas
      contribution from the SCS and 56-d nonreturn as primiparous cow was negligible,
      after taking the other traits into account. This implies that for breeds selected
      for a broad breeding goal, including functional traits such as health and
      fertility, most of the genetic variation in culling will probably be covered by
      other traits in the breeding goal. However, in populations where data on health
      and fertility is scarce or not available at all, selection against early culling
      may be useful in indirect selection for improved health and fertility. Regression
      of average sire posterior mean on birth-year of the sire indicate a genetic
      change equivalent to an annual decrease of the probability of culling in first
      lactation Norwegian Red cattle by 0.2 percentage units. This genetic improvement
      is most likely a result of simultaneous selection for improved milk yield,
      health, and fertility over the last decades.

PMID- 18832227
TI  - Genetic correlation patterns between somatic cell score and protein yield in the
      Italian Holstein-Friesian population.
AB  - Genetic parameters for somatic cell score (SCS) in the Italian Holstein-Friesian
      population were estimated addressing the pattern of genetic correlation with
      protein yield in different parities (first, second, and third) and on different
      days in milk within each parity. Three approaches for parameter estimation were
      applied using random samples of herds from the national database of the Italian
      Holstein Association. Genetic correlations for lactation measures (305-d protein
      yield and lactation SCS) were positive in the first parity (0.31) and close to
      zero in the second (0.01) and third (0.09) parities. These results indicated that
      larger values of SCS were genetically associated with increased production. The
      second and third sets of estimates were based on random regression test-day
      models, modeling the shape of lactation curve with the Wilmink function and
      fourth-order Legendre polynomials, respectively. Genetic correlations from both
      random regression models showed a specific pattern associated with days in milk
      within and across parities. Estimates varied from positive to negative in the
      first and second parity, and from null to negative in the third parity. Patterns
      were similar for both random regression models. The average overall correlation
      between SCS and protein yield was zero or slightly positive in the first
      lactation and ranged from zero to negative in later lactations. Correlation
      estimates differed by parity and stage of lactation. They also demonstrated the
      dubiousness of applying a single genetic correlation measure between SCS and
      protein in setting selection strategies. Differences in magnitude and the sign of
      genetic correlations between SCS and yields across and within parities should be
      accounted for in selection schemes.

PMID- 18832228
TI  - Effects of composite beta- and kappa-casein genotypes on milk coagulation,
      quality, and yield traits in Italian Holstein cows.
AB  - The aim of the study was to estimate the effect of the composite CSN2 and CSN3
      genotypes on milk coagulation, quality, and yield traits in Italian Holstein
      cows. A total of 1,042 multiparous Holstein cows reared on 34 commercial dairy
      herds were sampled once, concurrently with monthly herd milk recording. The data
      included the following traits: milk coagulation time; curd firmness; pH and
      titratable acidity; fat, protein, and casein contents; somatic cell score; and
      daily milk, fat, and protein yields. A single-trait animal model was assumed with
      fixed effects of herd, days in milk, parity, composite casein genotype of CSN2
      and CSN3 (CSN2-CSN3), and random additive genetic effect of an animal. The
      composite genotype of CSN2-CSN3 showed a strong effect on both milk coagulation
      traits and milk and protein yields, but not on fat and protein contents and other
      milk quality traits. For coagulation time, the best CSN2-CSN3 genotypes were
      those with at least one B allele in both the CSN2 and CSN3 loci. The CSN3 locus
      was associated more strongly with milk coagulation traits, whereas the CSN2 locus
      was associated more with milk and protein yields. However, because of the tight
      linkage between the 2 loci, the composite genotypes, or haplotypes, are more
      appropriate than the single-locus genotypes if they were considered for use in
      selection.

PMID- 18832229
TI  - Detection of quantitative trait loci in Danish Holstein cattle affecting clinical
      mastitis, somatic cell score, udder conformation traits, and assessment of
      associated effects on milk yield.
AB  - The aim of this study was to 1) detect QTL across the cattle genome that
      influence the incidence of clinical mastitis and somatic cell score (SCS) in
      Danish Holsteins, and 2) characterize these QTL for pleiotropy versus multiple
      linked quantitative trait loci (QTL) when chromosomal regions affecting clinical
      mastitis were also affecting other traits in the Danish udder health index or
      milk production traits. The chromosomes were scanned using a granddaughter design
      where markers were typed for 19 to 34 grandsire families and 1,373 to 2,042 sons.
      A total of 356 microsatellites covering all 29 autosomes were used in the scan.
      Among the across-family regression analyses, 16 showed chromosome-wide
      significance for the primary traits incidence of clinical mastitis in first
      (CM1), second (CM2), and third (CM3) lactations, and SCS. Regions of chromosomes
      5, 6, 9, 11, 15, and 26 were found to affect CM and regions of chromosomes 5, 6,
      8, 13, 22, 23, 24, and 25 affected SCS. Markers on chromosomes 6, 11, 15, and 26
      can be used to perform marker-assisted selection on CM without a direct negative
      selection on milk yield, because no effects were detected on the milk traits.
      Comparing multi-trait models assuming either a pleiotropic QTL affecting 2 traits
      or 2 QTL each affecting 1 trait gave some evidence to distinguish between these
      models. For Bos taurus autosome 5, the most likely models were a pleiotropic QTL
      affecting CM2, CM3, and SCS, and a linked QTL affecting fat yield index. For Bos
      taurus autosome 9, the most likely model is a pleiotropic QTL affecting CM1 and
      CM2 at approximately 8 cM.

PMID- 18832230
TI  - Genetic parameters for digital dermatitis and correlations with locomotion,
      production, fertility traits, and longevity in Holstein-Friesian dairy cows.
AB  - Heritability of digital dermatitis (DD) and correlations between DD and type
      traits related to legs and feet were estimated from a linear animal model. Data
      comprised 93,391 national type evaluation records of pedigreed first-lactation
      Holstein-Friesian cows that calved from 2002 through 2006. At the time of
      classification, cows were housed in different housing systems (i.e., cubicles,
      straw yards, slatted or loafing yards) and on pasture. The type traits evaluated
      were locomotion score (LOCO), rear legs side view (RLS), foot angle (FA), bone
      quality and leg and feet composite (L&F). In addition, cows were examined for DD
      lesions at classification. The relationships among these type traits, lifespan
      (LS), production (milk and fat), fertility (calving interval and 56-d nonreturn)
      and DD were examined by estimating the approximate genetic correlations from sire
      estimated breeding values. The study also evaluated the association between DD
      and the housing systems as well as the general conditions of the farm flooring
      where classification took place. In general, cows on pasture were less
      susceptible to DD than cows in other housing systems, whereas the association
      between DD and the flooring conditions was counterintuitive. Heritability
      estimate for DD was 0.011 on the 0/1 scale, which is equivalent to 0.029 on the
      assumed underlying normally distributed scale. Bone quality, LOCO, and L&F had
      moderate to high negative genetic correlations with DD, indicating that flatter,
      more refined bones, higher LOCO, and better L&F were associated with less
      incidence of DD. The genetic correlations between DD, RLS, and FA were not
      significantly different from zero. Digital dermatitis had moderate but negative
      genetic correlations with LS and milk and fat, suggesting that breeding for
      resistance to DD will result in an increase in both longevity and production.
      Cows affected with DD had a slightly shorter calving interval than healthy cows,
      an association found to be mediated through the reduced milk yield of these cows.
      Generally, the type traits included in this study had low genetic correlations
      with production and fertility traits whereas the associations between these
      traits and LS ranged from moderate to high. This indicates that good locomotion,
      straighter RLS, steeper FA, better L&F, and flatter, more refined bones are
      associated with increased longevity.

PMID- 18832231
TI  - Genetic correlation between female fertility and milk yield in Lacaune sheep.
AB  - A total of 416,670 lactations for 189,101 ewes from 3,603 sires and distributed
      across 1,978 herd-year groups were used to estimate genetic and environmental
      parameters of standardized milk yield (SMY(T)), fertility in ewe lambs (PR(1)),
      and fertility in adult ewes (PR(A)). Parameters were estimated with a multiple
      trait sire linear model. Heritabilities for SMY(T), PR(1), and PR(A) were 0.27
      (0.009), 0.04 (0.004), and 0.05 (0.004), respectively. These results were in
      accordance with the literature. The genetic correlation between PR(1) and PR(A)
      was 0.55, indicating that fertility is not the same trait in ewe lambs and adult
      ewes. The genetic correlation between milk yield and lamb fertility was not
      significantly different from zero. The genetic correlation between milk yield and
      fertility in adult ewe (-0.23) was in the range of antagonistic correlations
      reported in dairy cattle. Consequently, these results show that selection for
      milk yield can induce an indirect decrease in fertility. Nevertheless, no
      phenotypic decrease in fertility in artificial insemination matings has been
      observed in this population. This is the first time that correlation between milk
      yield and fertility is reported in sheep and further investigations are needed to
      confirm this result.

PMID- 18832232
TI  - Technical note: detection of the C allele of beta-casein (CSN2) in Czech Dairy
      goat breeds using LightCycler analysis.
AB  - A protocol was developed for rapid genotyping of A and C variants at the CSN2
      locus in goat species (White Shorthaired and Brown Shorthaired goat) by PCR and
      LightCycler analysis. The LightCycler technique combines rapid and efficient in
      vitro amplification of DNA in glass capillaries, with melting curve analysis
      based on fluorescence resonance energy transfer, for the sensitive detection of
      point mutation. Analysis of the CSN2 variability in the 2 goat breeds reared in
      the Czech Republic validated the genotyping test. Monitoring of CSN2 variability
      in the goat breeds indicates the predominance of the C allele. In both breeds,
      CSN2*A and CSN2*C showed almost similar frequencies. Variant CSN2*C occurred with
      a frequency of 0.699 in White Shorthaired goats and 0.570 in Brown Short-haired
      goats.

PMID- 18832233
TI  - Technical note: adaptation of an animal-model method for approximation of
      reliabilities to a sire-maternal grandsire model.
AB  - A method used to approximate reliabilities for animal models was modified to
      estimate reliabilities for sire-maternal grandsire (MGS) models. Accuracy of the
      approximation was tested on a calving-ease data set for 2,968 bulls for which the
      inverse of the coefficient matrix could be obtained. Correlations between
      estimated and true reliabilities ranged from 0.984 to 0.998 for first- and later
      parity calving ease for sire and MGS effects. With no modification of the animal
      model procedure, MGS identification was treated as if it were dam identification,
      which resulted in overestimated reliability. When pedigree information was
      ignored, reliability was underestimated. Correlations with true values were lower
      for both of those cases when compared with correct processing of MGS information.
      The modification provided a slight improvement over assuming MGS to be unknown
      and will be used for routine USDA evaluation of calving traits.

PMID- 18832234
TI  - Effect of prehydrolysis of milk fat on its conversion to biogas.
AB  - Milk fat is considered to be the main limiting component of the kinetics of dairy
      wastewater anaerobic digestion. The objective of this work was to give a better
      understanding of the nonelucidated anaerobic degradation steps of milk fat. For
      that purpose, the kinetics of fat degradation was quantified in comparison with
      other milk components (lactose, proteins), regarding the milk fat polluting load
      and structure [globular (native state), triglycerides]. This work confirms that
      milk fat is degraded after a lag phase of several days, with a maximal
      degradation rate 2 to 5 times less than the degradation rate of the other milk
      components. It was shown that (1) the structure of the fat does not influence the
      limits of its anaerobic degradation; (2) the lag phase before biogas production
      is mainly due to unsaturated free fatty acids (FFA); and (3) conversion to biogas
      occurs at a lower rate for saturated than for unsaturated FFA. Therefore, the
      prehydrolysis of fat, which increases the instantaneous concentration of
      unsaturated FFA, sharply increases the length of the lag phase with no
      significant change in the maximal biogas production rate. To reduce the delay
      imposed in the biogas production, it is necessary to reduce the concentration of
      unsaturated FFA.

PMID- 18832235
TI  - Identification and antimicrobial resistance of Streptococcus uberis and
      Streptococcus parauberis isolated from bovine milk samples.
AB  - The conventional identification of Streptococcus uberis/parauberis group (n =
      137) in clinical and subclinical bovine mastitis samples originating from 111
      different farms was compared with identification based on 16 and 23S rRNA gene
      HindIII RFLP patterns used as operational taxonomic units in numerical analyses.
      On the basis of ribopattern analysis only 2 isolates belonged to S. parauberis,
      which is thus not a frequent cause of bovine intramammary infections in Finland.
      According to in vitro antimicrobial susceptibility testing, Streptococcus uberis
      is susceptible to beta-lactam antibiotics. The prevalence of erythromycin (15.6%)
      and oxytetracycline (40.6%) resistance of clinical S. uberis isolates was higher
      than reported previously among subclinical isolates. The 2 subclinical S.
      parauberis isolates were susceptible to all the antimicrobials tested.

PMID- 18832236
TI  - Economic analysis of reproductive management strategies on US commercial dairy
      farms.
AB  - Reproductive management has received increased attention in recent years as new
      technologies and programs have been developed to aid dairy managers in
      efficiently breeding cows and heifers. Efficient breeding of cows and heifers has
      become increasingly difficult as fertility has decreased because of a correlated
      negative response with milk yield. Dairy farm survey results were used to
      parameterize the economic analyses of reproductive management programs.
      Reproductive management program costs and the levels of reproductive performance
      achieved with such programs varied significantly among farms and were especially
      sensitive to on-farm labor costs. For example, visual heat detection requires
      more hours of labor per cow than use of an estrus synchronization program.
      Therefore, visual heat detection programs were relatively more sensitive to labor
      costs than synchronization programs. In addition, past reproductive performance
      was found to affect the determination of which reproductive program was optimal.
      Farms that had attained high levels of labor efficiency for visual heat detection
      in the past had less incentive to adopt a synchronization program than farms with
      less efficient visual heat detection.

PMID- 18832237
TI  - Effect of Holstein Friesian and Brown Swiss breeds on quality of milk and cheese.
AB  - In Italy, more than 75% of milk is used for cheese making. For this reason, milk
      composition and coagulation traits and cheese quality represent the most
      important tools for the economic development of the dairy sector. In particular,
      cheese quality varies in relation to cheese-making technology and breed of cow.
      The aim of this study was to investigate the effect of 3 types of milk,
      originating from Holstein-Friesian (HF), Brown Swiss (BS), and mixed of both
      breeds, on vat milk characteristics, cheese yield, and quality in 3 different
      typical Italian cheese-making conditions (Casolet, Vezzena, and Grana Trentino).
      One hundred forty-four cows (66 HF and 78 BS) were involved, and a total of 24
      vats of milk were evaluated. At maturity, 30, 21, and 16 wheels of Casolet,
      Vezzena, and Grana Trentino cheese were analyzed. Brown Swiss cows yielded 9%
      less milk per day than HF cows, but milk showed greater contents of protein,
      casein, titratable acidity, and better rennet coagulation time and curd firmness
      than HF milk. The chemical composition and cholesterol content of the 3 types of
      cheese were similar between breeds, whereas the cheese made with BS milk showed
      greater contents of monounsaturated and polyunsaturated fatty acids. Cheese made
      with BS milk had greater b* (yellow component) than HF. Cheese yield, recorded at
      different ripening times, demonstrated that BS milk yielded more cheese than HF.
      Mixed milk showed values, on average, intermediate to HF and BS milk
      characteristics, and this trend was confirmed in cheese yield at different
      ripening times.

PMID- 18832238
TI  - Reproducibility and repeatability of measures of milk coagulation properties and
      predictive ability of mid-infrared reflectance spectroscopy.
AB  - The objectives of the study were to estimate the reproducibility and
      repeatability of milk coagulation properties (MCP) measured by a computerized
      renneting meter (CRM) and to evaluate the predictive ability of mid-infrared
      spectroscopy (MIRS) as an innovative technology for the assessment of rennet
      coagulation time (RCT, min) and curd firmness (a(30), mm). Four samples without
      addition of preservative (NP) and 4 samples with Bronopol addition (PS) were
      collected from each of 83 Holstein-Friesian cows. Six hours after collection, 2
      replicated measures of MCP were obtained with CRM using 1 NP and 1 PS sample from
      each cow. Mid-infrared spectra of the remaining NP and PS samples from each
      animal were recorded after 6 h, 4 d, and 8 d after sampling. Two groups of
      calibration equations were developed using MIRS spectra and CRM measures of MCP
      as reference data obtained from analysis of NP and PS, respectively.
      Reproducibility and repeatability of CRM measures were obtained from REML
      estimation of variance components on the basis of a linear model including the
      fixed effects of herd and days in milk class and the random effects of cows,
      sample treatment (addition or no addition of preservative), and the interaction
      between cow and sample treatment. Coefficient of reproducibility is an indicator
      of the agreement between 2 measurements of MCP for the same milk sample preserved
      with or without addition of Bronopol. Coefficient of repeatability is an
      indicator of the agreement between repeated measures of MCP. Pearson correlations
      between MCP measures for NP and PS were 0.97 and 0.83 for RCT and a(30),
      respectively. Reproducibility of CRM measures under different preserving
      conditions of milk was 93.5% for RCT and 64.6% for a(30). Repeatabilities of RCT
      and a(30) measures were 95.7 and 77.3%, respectively. Based on the estimated
      cross-validation standard errors and coefficients of determination and ratios of
      standard errors of cross-validation to standard deviation of reference data, the
      predictive ability of MIRS calibration equations was moderate for RCT and
      unsatisfactory for a(30.) Predictive ability of equations based on spectra and
      MCP measures of PS was greater than that of equations based on data of NP. The
      study did not provide conclusive evidence on the effectiveness of MIRS as a
      predictive tool for MCP and it requires an enlargement of the variability of milk
      sampling circumstances. Because the relevance of MIRS predictions in relation to
      breeding programs for MCP based on indicator traits relies on the genetic
      variation of MIRS predictions and on phenotypic and genetic correlations between
      MIRS predictions and MCP measures, additional specific investigations on these
      topics are needed.

PMID- 18832239
TI  - Single reading with computer-aided detection for screening mammography.
AB  - BACKGROUND: The sensitivity of screening mammography for the detection of small
      breast cancers is higher when the mammogram is read by two readers rather than by
      a single reader. We conducted a trial to determine whether the performance of a
      single reader using a computer-aided detection system would match the performance
      achieved by two readers. METHODS: The trial was designed as an equivalence trial,
      with matched-pair comparisons between the cancer-detection rates achieved by
      single reading with computer-aided detection and those achieved by double
      reading. We randomly assigned 31,057 women undergoing routine screening by film
      mammography at three centers in England to double reading, single reading with
      computer-aided detection, or both double reading and single reading with computer
      aided detection, at a ratio of 1:1:28. The primary outcome measures were the
      proportion of cancers detected according to regimen and the recall rates within
      the group receiving both reading regimens. RESULTS: The proportion of cancers
      detected was 199 of 227 (87.7%) for double reading and 198 of 227 (87.2%) for
      single reading with computer-aided detection (P=0.89). The overall recall rates
      were 3.4% for double reading and 3.9% for single reading with computer-aided
      detection; the difference between the rates was small but significant (P<0.001).
      The estimated sensitivity, specificity, and positive predictive value for single
      reading with computer-aided detection were 87.2%, 96.9%, and 18.0%, respectively.
      The corresponding values for double reading were 87.7%, 97.4%, and 21.1%. There
      were no significant differences between the pathological attributes of tumors
      detected by single reading with computer-aided detection alone and those of
      tumors detected by double reading alone. CONCLUSIONS: Single reading with
      computer-aided detection could be an alternative to double reading and could
      improve the rate of detection of cancer from screening mammograms read by a
      single reader. (ClinicalTrials.gov number, NCT00450359.)

PMID- 18832240
TI  - Images in clinical medicine. Pneumopericardium.

PMID- 18832241
TI  - Still in the game--harnessing employer inventiveness in U.S. health care reform.

PMID- 18832242
TI  - Executive physicals--bad medicine on three counts.

PMID- 18832243
TI  - The statins in preventive cardiology.

PMID- 18832246
TI  - Clinical practice. Autosomal dominant polycystic kidney disease.

PMID- 18832244
TI  - Maraviroc for previously treated patients with R5 HIV-1 infection.
AB  - BACKGROUND: CC chemokine receptor 5 antagonists are a new class of antiretroviral
      agents. METHODS: We conducted two double-blind, placebo-controlled, phase 3
      studies--Maraviroc versus Optimized Therapy in Viremic Antiretroviral Treatment
      Experienced Patients (MOTIVATE) 1 and MOTIVATE 2--with patients who had R5 human
      immunodeficiency virus type 1 (HIV-1) only. They had been treated with or had
      resistance to three antiretroviral-drug classes and had HIV-1 RNA levels of more
      than 5000 copies per milliliter. The patients were randomly assigned to one of
      three antiretroviral regimens consisting of maraviroc once daily, maraviroc twice
      daily, or placebo, each of which included optimized background therapy (OBT)
      based on treatment history and drug-resistance testing. Safety and efficacy were
      assessed after 48 weeks. RESULTS: A total of 1049 patients received the randomly
      assigned study drug; the mean baseline HIV-1 RNA level was 72,400 copies per
      milliliter, and the median CD4 cell count was 169 per cubic millimeter. At 48
      weeks, in both studies, the mean change in HIV-1 RNA from baseline was greater
      with maraviroc than with placebo: -1.66 and -1.82 log(10) copies per milliliter
      with the once-daily and twice-daily regimens, respectively, versus -0.80 with
      placebo in MOTIVATE 1, and -1.72 and -1.87 log(10) copies per milliliter,
      respectively, versus -0.76 with placebo in MOTIVATE 2. More patients receiving
      maraviroc once or twice daily had HIV-1 RNA levels of less than 50 copies per
      milliliter (42% and 47%, respectively, vs. 16% in the placebo group in MOTIVATE
      1; 45% in both maraviroc groups vs. 18% in MOTIVATE 2; P<0.001 for both
      comparisons in each study). The change from baseline in CD4 counts was also
      greater with maraviroc once or twice daily than with placebo (increases of 113
      and 122 per cubic millimeter, respectively, vs. 54 in MOTIVATE 1; increases of
      122 and 128 per cubic millimeter, respectively, vs. 69 in MOTIVATE 2; P<0.001 for
      both comparisons in each study). Frequencies of adverse events were similar among
      the groups. CONCLUSIONS: Maraviroc, as compared with placebo, resulted in
      significantly greater suppression of HIV-1 and greater increases in CD4 cell
      counts at 48 weeks in previously treated patients with R5 HIV-1 who were
      receiving OBT. (ClinicalTrials.gov numbers, NCT00098306 and NCT00098722.)

PMID- 18832247
TI  - Hepatitis B virus infection.

PMID- 18832248
TI  - Images in clinical medicine. Ludwig's angina.

PMID- 18832249
TI  - Clinical problem-solving. Variations on a theme.

PMID- 18832250
TI  - A new class of anti-HIV therapy and new challenges.

PMID- 18832245
TI  - Subgroup analyses of maraviroc in previously treated R5 HIV-1 infection.
AB  - BACKGROUND: We conducted subanalyses of the combined results of the Maraviroc
      versus Optimized Therapy in Viremic Antiretroviral Treatment-Experienced Patients
      (MOTIVATE) 1 and MOTIVATE 2 studies to better characterize the efficacy and
      safety of maraviroc in key subgroups of patients. METHODS: We analyzed pooled
      data from week 48 from the two studies according to sex, race or ethnic group,
      clade, CC chemokine receptor 5 (CCR5) delta32 genotype, viral load at the time of
      screening, the use or nonuse of enfuvirtide in optimized background therapy
      (OBT), the baseline CD4 cell count, the number of active antiretroviral drugs
      coadministered, the first use of selected background agents, and tropism at
      baseline. Changes in viral tropism and the CD4 count at treatment failure were
      evaluated. Data on aminotransferase levels in patients coinfected with hepatitis
      B virus (HBV) or hepatitis C virus (HCV) were also analyzed. RESULTS: A treatment
      benefit of maraviroc plus OBT over placebo plus OBT was shown in all subgroups,
      including patients with a low CD4 cell count at baseline, those with a high viral
      load at screening, and those who had not received active agents in OBT. Analyses
      of the virologic response according to the first use of selected background drugs
      showed the additional benefit of adding a potent new drug to maraviroc at the
      initiation of maraviroc therapy. More patients in whom maraviroc failed had a
      virus binding to the CXC chemokine receptor 4 (CXCR4) at failure, but there was
      no evidence of a decrease in the CD4 cell count at failure in such patients as
      compared with those in whom placebo failed. Subanalyses involving patients
      coinfected with HBV or HCV revealed no evidence of excess hepatotoxic effects as
      compared with baseline. CONCLUSIONS: Subanalyses of pooled data from week 48
      indicate that maraviroc provides a valuable treatment option for a wide spectrum
      of patients with R5 HIV-1 infection who have been treated previously.
      (ClinicalTrials.gov numbers, NCT00098306 and NCT00098722.)

PMID- 18832251
TI  - Toxic tinkering--lethal-injection execution and the Constitution.

PMID- 18832252
TI  - Intensive glucose control in type 2 diabetes.

PMID- 18832253
TI  - Rhythm control versus rate control for atrial fibrillation.

PMID- 18832254
TI  - In utero and early-life conditions and adult health and disease.

PMID- 18832255
TI  - A case of conjugal azathioprine-induced contact hypersensitivity.

PMID- 18832256
TI  - Dengue hemorrhagic fever transmitted by blood transfusion.

PMID- 18832257
TI  - Aliskiren for hypertension in adults.
AB  - High blood pressure is a major risk factor for cardiovascular disease worldwide.
      Drug treatments include those that target the renin-angiotensin system, a key
      hormone cascade in the regulation of blood pressure. One of these is aliskiren
      (Rasilez - Novartis), which belongs to a new class of drugs, direct renin
      inhibitors. Here we assess its place in managing adults with hypertension.

PMID- 18832258
TI  - Retapamulin for impetigo and other infections.
AB  - Last year, we concluded that topical fusidic acid should be first-line treatment
      for impetigo. Since then, retapamulin ointment (Altargo - GlaxoSmithKline), a new
      antibacterial, has been licensed in the European Union as a short-term treatment
      for impetigo and infected small lacerations, abrasions or sutured wounds in
      people aged 9 months or above. Advertisements claim that the product "treats
      localised impetigo in just 5 days"; by comparison, the British National Formulary
      (BNF) advises a 7-day course of fusidic acid. Here we consider the place of
      retapamulin in impetigo and its other licensed indications.

PMID- 18832259
TI  - Erdosteine for COPD exacerbations.
AB  - The mucolytic drug erdosteine (Erdotin - Galen) is licensed in the UK as
      treatment for up to 10 days "for the symptomatic treatment of acute exacerbations
      of chronic bronchitis in adults". This indication differs from that for
      carbocisteine and mecysteine, two older mucolytic drugs that are licensed for
      adjunctive treatment in respiratory disorders characterised by viscous mucus, and
      typically used for longer to prevent exacerbations of chronic obstructive
      pulmonary disease (COPD). Does erdosteine have a role for people with COPD
      exacerbations?

PMID- 18832260
TI  - Pathogenesis as the basis for disease prevention: a worthwhile pursuit.

PMID- 18832261
TI  - Joining the health care discussion.

PMID- 18832262
TI  - Electrosurgery.

PMID- 18832263
TI  - Cancer screening.

PMID- 18832265
TI  - Optical protein sensor detects disease in saliva.

PMID- 18832266
TI  - Xylitol gummy bears reduce plaque in young children.

PMID- 18832267
TI  - Esthetics and smile characteristics from the layperson's perspective: a computer
      based survey study.
AB  - BACKGROUND: The paradigm shift from occlusion to esthetics places more emphasis
      on the subtle relationships among the teeth and the interplay with the soft
      tissues. The authors of this study quantified the ideal and maximum acceptable
      deviations for smile characteristics. METHODS: The authors created a survey by
      using a digital image editing software package, which enabled raters to
      manipulate intraoral photographs featured in the survey. They altered smile
      characteristics in photos of a sex-neutral face showing nasal tip to mentolabial
      fold. The authors administered an electronic survey in Boston (n = 78); Columbus,
      Ohio (n = 81); and Seattle (n = 84). An interactive interface allowed raters to
      select the ideal for each smile characteristic presented and identify the range
      of acceptability for the variables. RESULTS: Raters were reliable (kappa = 0.34
      0.88). Survey location was not significant except that raters from the West
      accepted a broader smile than did those from the Midwest and the East. Raters
      identified ideals and thresholds for the following smile characteristics: smile
      arc; buccal corridor; gingival display; canine and posterior crown torque, ideal
      and large corridor; maxillary midline to face; maxillary to mandibular midline;
      overbite; maxillary central incisor gingival height discrepancy; maxillary
      lateral incisor gingival height discrepancy; maxillary central to lateral incisal
      step; maxillary central incisor crown width-to-height ratio; maxillary central-to
      lateral incisal ratio; and occlusal cant. Generally, the values for ideal
      paralleled existing data, and new guidelines for some variables emerged. The
      ranges of acceptability were large. CONCLUSIONS: The ideal and an acceptable
      range for each smile characteristic can be identified reliably. PRACTICE
      IMPLICATIONS: Laypeople can reliably identify ideal smile characteristics. The
      ranges of acceptable deviations for smile characteristics are large, and
      practitioners should avoid unnecessarily sensitizing patients to minor
      discrepancies.

PMID- 18832268
TI  - Methicillin-resistant Staphylococcus aureus: a primer for dentists.
AB  - BACKGROUND AND OVERVIEW: In 2005 in the United States, an estimated 94,370 new,
      invasive infections and 18,650 deaths were associated with methicillin-resistant
      Staphylococcus aureus (MRSA); most of these infections were in people with
      exposures in health care settings. MRSA also has emerged as a community-based
      pathogen, causing primarily skin infections that are not life-threatening, but
      occasionally causing more severe and invasive infections. The authors describe
      the history of MRSA; identify populations at greatest risk of experiencing MRSA
      colonization and infection; compare characteristics of MRSA infections occurring
      in health care and community settings; and summarize strategies, based on U.S.
      Centers for Disease Control and Prevention recommendations and the literature, to
      prevent transmission of MRSA in dental offices. CONCLUSIONS AND CLINICAL
      IMPLICATIONS: Standard infection control precautions should be enforced strictly
      in all ambulatory care settings, including dental offices, to prevent facility
      based transmission of MRSA and other infectious agents.

PMID- 18832269
TI  - Oral lesions in patients participating in an oral examination screening week at
      an urban dental school.
AB  - BACKGROUND: Dental education must emphasize early diagnosis and management of
      oral mucosal disease, including early detection of oral premalignant lesions and
      cancer. The authors evaluated clinical findings of oral screening examinations of
      dental patients during a one-week period in an urban dental school clinic.
      METHODS: Third- and fourth-year dental students conducted clinical screening
      examinations for all dental patients of record seen during the Yul Brynner
      Foundation's Oral, Head and Neck Cancer Awareness Week in April 2006. RESULTS: Of
      262 patients, 100 (38.2 percent) reported that they had used tobacco for a mean
      of 8.1 years. Most patients reported having denture or tooth and gingival
      problems. The dental students reported abnormal findings in 55 patients (21
      percent). Two patients had suspected premalignant lesions that were diagnosed as
      lichen planus and traumatic keratosis. CONCLUSIONS AND CLINICAL IMPLICATIONS: The
      one-week screening provided an educational opportunity for the dental students,
      and the results demonstrate the value of having a focused week to reinforce the
      importance of head and neck and oral soft-tissue examination. The finding of
      mucosal lesions in 21 percent of patients of record reflects the fact that
      lesions were present but undetected. In addition, there are important
      implications for teaching and patient care. The screening week provided an
      opportunity for students to be active in a national campaign for cancer
      detection, and it represents an opportunity for visible community participation
      in the recognition of oral mucosal diseases in dental training programs and
      broadly for the profession.

PMID- 18832270
TI  - Exploring the reasons for delay in treatment of oral cancer.
AB  - BACKGROUND: Oral cancer continues to be diagnosed and treated at a late stage,
      which has a negative effect on outcomes. This study identified and quantified
      delays in diagnosis and treatment. METHODS: The authors conducted a study that
      included all new patients seen in the Department of Oral and Maxillofacial
      Surgery, University of California, San Francisco, between 2003 and 2007 who had a
      diagnosis of squamous cell carcinoma of the oral cavity. They identified the time
      intervals for six stages, beginning with the time at which patients first became
      aware of symptoms and ending with the time at which definitive treatment began.
      RESULTS: The total time from patients' first sign or symptoms to commencement of
      treatment was a mean of 205.9 days (range, 52-786 days). The longest delay was
      from the time symptoms first appeared to the initial visit to a health care
      professional (mean time, 104.7 days; range, 0-730 days). CONCLUSIONS: Health care
      professionals need to place greater emphasis on patient education to encourage
      early self-referrals. CLINICAL IMPLICATIONS: Patients should be encouraged to
      visit a health care professional when signs or symptoms of oral cancer first
      develop.

PMID- 18832271
TI  - Gingival retraction techniques for implants versus teeth: current status.
AB  - BACKGROUND: The authors reviewed and compared gingival retraction techniques used
      for implants and teeth. TYPES OF STUDIES REVIEWED: The authors searched the
      literature using article databases Ovid MEDLINE up to May 2008, PubMED and Google
      Scholar (advanced search) and the following search terms: gingival retraction,
      implant abutment, impressions, cement-retained implant restoration, impression
      coping, peri-implant tissue, emergence profile and tissue conditioning. RESULTS:
      The authors found insufficient evidence relating to gingival displacement
      techniques for impression making for implant dentistry. Gingival retraction
      techniques and materials are designed primarily for peridental applications; the
      authors considered their relevance to peri-implant applications and determined
      that further research and new product development are needed. CLINICAL
      IMPLICATIONS: The use of injectable materials that form an expanding matrix to
      provide gingival retraction offers effective exposure of preparation finish lines
      and is suitable for conventional impression-making methods or computer-aided
      design/computer-aided manufacturing digital impressions in many situations. There
      are, however, limitations with any retraction technique, including injectable
      matrices, for situations in which clinicians place deep implants.

PMID- 18832272
TI  - Altering the gag reflex via a palm pressure point.
AB  - BACKGROUND: The gag reflex regularly interferes with dental procedures. The
      authors hypothesize that applying pressure to a specific point on the palm alters
      the gag reflex and that hypersensitive gag reflexes may be categorized according
      to oropharyngeal landmarks. METHODS: Thirty-six neurologically intact subjects
      underwent a series of gag reflex trials (baseline, sham and treatment). The
      authors developed a hand pressure device for subjects to wear, which provided a
      consistent force, and they described a gag trigger point index (GTPI) scale. On
      the basis of the GTPI, they divided subjects into a hypersensitive group and an
      expected-sensitivity (control) group. RESULTS: The trigger point of the gag
      reflex moved posteriorly in all subjects as a result of pressure to the palm
      point. Statistical results from repeated measures analysis of variance support
      the GTPI baseline data, and group assignments helped predict mean GTPI scores
      across conditions. The authors noted a significant treatment-group interaction
      effect, which indicated that the difference in mean GTPI responses between the
      hypersensitive and expected-sensitivity groups depended on the treatment being
      used. CONCLUSIONS: The authors introduce a treatment involving the stimulation of
      a pressure point that consistently altered the gag reflex trigger. The results of
      the study show the need for a more detailed, systematic approach to studying the
      hypersensitive gag reflex. CLINICAL IMPLICATIONS: The change in trigger point in
      the hypersensitive group represented a functional gain. Application of the
      pressure point during dental procedures would decrease the likelihood of
      triggering a gag reflex.

PMID- 18832273
TI  - The correlation of DIFOTI to clinical and radiographic images in Class II carious
      lesions.
AB  - BACKGROUND: The authors conducted a study to evaluate the correlation between
      digital imaging fiber-optic transillumination (DIFOTI) (KaVo Dental, Lake Zurich,
      Ill.) and clinical and radiographic images in estimating the true clinical axial
      extension of Class II carious lesions. METHODS: The authors examined 51 Class II
      carious lesions visually, imaged them by means of DIFOTI and radiographed them
      with D-speed film and a complementary metal oxide silicon (CMOS)-based digital
      radiographic sensor. They validated axial extension of the lesions clinically.
      They compared the clinical and radiographic depths of the carious lesion with the
      size of the lesion on the DIFOTI images. RESULTS: The authors detected 84 percent
      of the lesions with DIFOTI, and 82 percent showed a visible dark shadow under the
      marginal ridge when examined clinically. DIFOTI correlated significantly with the
      clinical depth of decay (Pearson r = 0.43189). The combination of a CMOS digital
      sensor and DIFOTI (R2 = 0.7210) provided readings closer to the clinical measures
      than did the combination of D-speed film and DIFOTI (R2 = 0.6215). CONCLUSIONS:
      DIFOTI images correlated with clinical depth, especially in smaller lesions, and
      improved the estimation of lesion size when used in conjunction with the CMOS
      digital sensor and D-speed images. CLINICAL IMPLICATIONS: Using radiographs in
      combination with DIFOTI images could help clinicians determine the presence and,
      to some extent, the size of proximal caries, especially in smaller lesions.

PMID- 18832274
TI  - Improving oral health behavior: a social psychological approach.
AB  - BACKGROUND: The authors describe social psychological research that has found
      consistent beneficial effects of framing health messages to be congruent with
      personality factors in encouraging preventive oral health behaviors. METHODS: The
      authors describe several studies in which they administered health messages to
      young adults who did not floss and who were classified as predominantly approach
      oriented or avoidance-oriented on the basis of a short personality questionnaire.
      They framed the messages to emphasize the benefits of dental flossing or the
      costs of not flossing. The authors assessed the effectiveness in terms of
      flossing efficacy and flossing behavior. RESULTS: When patients received a dental
      health message that was congruent with their motivational orientation-approach or
      avoidance-they had a stronger belief that they were capable of flossing,
      expressed greater intentions to floss and exhibited increased flossing behavior
      (flossing 50 to 65 percent more often in the following week). CONCLUSIONS: Two
      factors that dental practitioners should consider when delivering information are
      whether the patient is more approach- or avoidance-oriented and whether to frame
      the message in terms of gains or losses. CLINICAL IMPLICATIONS: Practitioners can
      use these theory-based findings in dental practice to promote positive oral
      health behaviors by administering brief personality assessments to patients and
      by framing the message accordingly.

PMID- 18832275
TI  - The relationship of periodontal disease to diseases and disorders at distant
      sites: communication to health care professionals and patients.
AB  - BACKGROUND: The body of research defining relationships among periodontal disease
      and certain systemic diseases and disorders has been expanding, and questions
      have been raised regarding what information should be conveyed to health care
      professionals and patients. METHODS: Representatives from dentistry, medicine,
      the academic community and the insurance industry convened a two-day workshop
      July 23 and 24, 2007. RESULTS: The workshop participants achieved general
      consensus on a number of issues, including the need for greater cooperation
      between the health care professions. This cooperation should translate into
      improved clinical care as physicians refer patients for dental care, and dentists
      are proactive in regard to the general health of their patients. CONCLUSION:
      Communication to health care professionals requires a multifaceted approach that
      includes publication of research findings in medical and dental journals,
      cooperation among professional organizations and initiatives at the local level
      such as presentations at medical grand rounds. Dental schools should play a role
      in their health science centers. Communication with patients may improve through
      the use of targeted informational brochures in the offices of medical
      specialists, appropriate media campaigns and efforts led by local dental
      organizations. PRACTICE IMPLICATIONS: It is too early to provide specific
      recommendations regarding the treatment of periodontal disease to improve
      specific health outcomes, but dentists can become advocates for a general health
      promotion and disease prevention message. The lifestyles approach includes an
      improved diet, smoking cessation, appropriate hygiene practices and stress
      reduction. These strategies can improve oral and general health outcomes.

PMID- 18832276
TI  - A patient with severe wear on the anterior teeth and minimal wear on the
      posterior teeth.

PMID- 18832277
TI  - Core values and practice success.

PMID- 18832278
TI  - What should I keep in mind when naming and marketing a practice?

PMID- 18832279
TI  - For the dental patient... Kicking the nicotine habit.

PMID- 18832282
TI  - Risk factors control in diabetes: the "real world" of clinical practice.

PMID- 18832283
TI  - Development of an online university-based Physical Activity and Obesity education
      program.
AB  - PURPOSE: The purpose of this article is to describe the development and
      implementation of an undergraduate university core course titled, Public Health
      Issues in Physical Activity and Obesity (KIN1304) at a diverse, urban university.
      METHODS: The course was designed to provide the scientific and public health
      information on obesity with a goal of prevention. Whereas the course was
      administered to college students, there are several applications within diabetes
      education where its content may be useful. RESULTS: The course is entirely
      Internet based (by means of WebCT Vista) and is a university core requirement for
      all undergraduate degree programs on campus. Development of such a course
      provides an opportunity to reach a large portion of the undergraduate population.
      CONCLUSION: Development of the Internet-based course, Public Health Issues in
      Physical Activity and Obesity (KIN1304) may be useful for educating a wide
      variety of people regarding the risks and prevention associated with obesity and
      diabetes.

PMID- 18832284
TI  - Low testosterone and the association with type 2 diabetes.
AB  - PURPOSE: The purpose of this article is to describe androgen deficiency in men,
      the consequences of this clinically underdiagnosed endocrine disorder, and its
      relationship to the metabolic syndrome and the association with type 2 diabetes.
      An overview of prevalence, screening, diagnosis, treatment, and monitoring of
      male hypogonadism is presented. Method Established guidelines were used to
      provide definition, diagnosis, treatment, and monitoring information for male
      hypogonadism. A literature review from 1990 to 2007 revealed study findings that
      identify the link between low testosterone in men and the development of type 2
      diabetes. The following databases were used to review and analyze the current
      literature: CINAHL, PubMed, and MEDLINE. RESULTS: An analysis of 26 studies was
      completed. The key findings in all of these studies show that there is a link
      between low levels of testosterone and an adverse metabolic profile (ie, obesity
      and insulin resistance). There is evidence that hypogonadism is associated with
      metabolic syndrome and type 2 diabetes in men. CONCLUSION: Male hypogonadism is a
      clinical condition that affects a significant number of men in the United States
      and can affect up to 50% of men diagnosed with type 2 diabetes. The implications
      for diabetes educators are two-fold: first, there is a high prevalence of low
      testosterone in men with type 2 diabetes, and second, educators need to have a
      better understanding of this disease state to provide instructional guidance for
      their patients and to coordinate care with other clinicians.

PMID- 18832285
TI  - Psychosocial factors related to diet among women with recent gestational
      diabetes: opportunities for intervention.
AB  - PURPOSE: This study investigated postpartum dietary behaviors among women with
      recent gestational diabetes mellitus (GDM), the cognitive and social factors
      related to these, and preferred types of lifestyle support, in order improve the
      development of diabetes prevention strategies for this group. METHODS:
      Participants were a random sample of 226 women diagnosed with GDM in the prior 6
      to 24 months. Telephone surveys were used to evaluate dietary behaviors, self
      efficacy, social support, perceived barriers to healthy eating, and preferred
      methods of lifestyle support. RESULTS: Only 5% of the respondents consumed 5
      servings/day of vegetables and 44% consumed 2 or more servings/day of fruit.
      Fried food was eaten at least twice per week by 26% of women and 50% usually
      consumed full-fat milk. Higher vegetable consumption was associated with self
      efficacy to cook healthy foods, reporting that a healthy diet is not a difficult
      change and that dislike of healthy foods by other household members is not a
      barrier. Fruit consumption was positively related to self-efficacy when busy and
      when not reporting a dislike of healthy foods by others at home. Advice from a
      dietitian and telephone support from a health educator were the most preferred
      forms of health assistance. CONCLUSIONS: Dietary risks factors are prevalent
      among women with recent GDM. Confidence and skills in cooking healthy foods,
      along with family food preferences and time pressures, are important influences
      on eating habits. Dietary change programs, informed by the beliefs and
      circumstances of this high-risk population, need to be developed.

PMID- 18832286
TI  - Meta-analysis of quality of life outcomes following diabetes self-management
      training.
AB  - PURPOSE: The purpose of this meta-analysis was to meet the need to quantify the
      influence of diabetes self-management training on quality of life (QOL) of adult
      diabetes patients. METHODS: Extensive literature searching located published and
      unpublished diabetes self-management intervention studies that measured QOL
      outcomes among at least 5 subjects with type 1 or 2 diabetes. Data were extracted
      from primary study reports which included interventions designed to improve
      diabetes self-management and adequate data to calculate effect sizes. Random
      effects meta-analytic procedures were used to estimate overall effects between
      treatment and control groups at outcome assessment and between baseline and
      outcome data for both treatment subjects and control subjects. RESULTS:
      Exhaustive searching yielded 20 comparisons across 1892 subjects. The comparisons
      between treatment and control group outcomes following interventions yielded an
      effect size of 0.281. The comparisons between treatment group at baseline and
      outcome measurement yielded an effect size of 0.312 to 0.313. Each of these
      effect sizes were statistically significant, meaning that the hypothesis that
      interventions to improve diabetes self-management results in increased QOL was
      supported. Control subjects did not experience improved QOL while participating
      in studies. CONCLUSIONS: These findings document that people with diabetes
      experience improved QOL from participation in diabetes self-management training
      programs. Future diabetes self-management intervention studies should include
      quality of life outcomes so that this important outcome can be further studied.
      After more primary studies are available, future meta-analyses can explore
      important moderator analyses.

PMID- 18832287
TI  - Implementing the community health worker model within diabetes management:
      challenges and lessons learned from programs across the United States.
AB  - PURPOSE: The purpose of this qualitative study was to examine methods of
      implementation of the community health worker (CHW) model within diabetes
      programs, as well as related challenges and lessons learned. METHODS: Semi
      structured interviews were conducted with program managers. Four databases
      (PubMed, CINAHL, ISI Web of Knowledge, PsycInfo), the CDC's 1998 directory of CHW
      programs, and Google Search Engine were used to identify CHW programs. Criteria
      for inclusion were: DM program; used CHW strategy; occurred in United States. Two
      independent reviewers performed content analyses to identify major themes and
      findings. Sixteen programs were assessed, all but 3 focused on minority
      populations. Most CHWs were recruited informally; 6 programs required CHWs to
      have diabetes. RESULTS: CHW roles and responsibilities varied across programs;
      educator was the most commonly identified role. Training also varied in terms of
      both content and intensity. All programs gave CHWs remuneration for their work.
      Common challenges included difficulties with CHW retention, intervention fidelity
      and issues related to sustainability. Cultural and gender issues also emerged.
      Examples of lessons learned included the need for community buy-in and the need
      to anticipate nondiabetes related issues. CONCLUSIONS: Lessons learned from these
      programs may be useful to others as they apply the CHW model to diabetes
      management within their own communities. Further research is needed to elucidate
      the specific features of this model necessary to positively impact health
      outcomes.

PMID- 18832288
TI  - Diabetes training of community health workers serving native Hawaiians and
      Pacific people.
AB  - PURPOSE: Training of community health workers (CHWs) serving Native Hawaiian and
      Pacific People about diabetes prevention, control, and management was identified
      as a priority in a needs assessment of health agencies in Hawaii. METHODS:
      Principles from Community-Based Participatory Research provided a framework to
      develop and implement a 4-hour training curriculum. The curriculum developers
      incorporated teaching strategies shown to be effective with this population and
      included culturally relevant material. Nineteen health organizations participated
      in the training that reached 111 CHWs over a 3-year period. RESULTS: Based on
      comparison of pre- and post-diabetes knowledge test results, the training
      participants showed significant gain in diabetes knowledge. CONCLUSIONS: A
      culturally tailored diabetes education gives CHWs the relevant knowledge and
      tools to participate in the delivery of diabetes education to a minority group
      experiencing disparate health outcomes. A community-based method facilitated
      development of seminar content and delivery strategies.

PMID- 18832289
TI  - Making diabetes self-management education culturally relevant for Filipino
      Americans in Hawaii.
AB  - PURPOSE: The purpose of this study was to identify the cultural values,
      traditions, and perceptions of diabetes risk and self-care among Filipino
      Americans in Hawaii with type 2 diabetes that facilitate or impede engagement in
      diabetes self-management behaviors and education classes. METHODS: This
      qualitative study used 2 rounds of semistructured focus groups and interviews.
      Participants included 15 patients with type 2 diabetes recruited from a large
      health-maintenance organization in Hawaii and 7 health care and cultural experts
      recruited from the community. The taped and transcribed focus groups and
      interviews were coded thematically. Participants evaluated example materials for
      diabetes self-management education (DSME) with Filipino Americans. RESULTS:
      Several aspects of Filipino American culture were identified as central to
      understanding the challenges of engaging in self-management behaviors and DSME:
      (1) undertaking self-management while prioritizing the family and maintaining
      social relationships, (2) modifying diet while upholding valued symbolic and
      social meanings of food, (3) participating in storytelling in the face of stigma
      associated with diabetes, and (4) reconciling spiritual and biomedical
      interpretations of disease causality and its management. Respondents also
      emphasized the role of several qualitative aspects of perceived risk (eg, dread,
      control) in moderating their behaviors. Participants suggested ways to make DSME
      culturally relevant. CONCLUSIONS: Awareness of cultural values and qualitative
      aspects of perceived risk that influence Filipino Americans' engagement in
      diabetes self-care behaviors and classes may help to improve teaching methods,
      materials, and recruitment strategies.

PMID- 18832290
TI  - Culturally tailored intervention for rural African Americans with type 2
      diabetes.
AB  - PURPOSE: The purpose of this pilot study was to evaluate a culturally tailored
      intervention for rural African Americans. Social Cognitive Theory provided the
      framework for the study. METHODS: Twenty-two participants were recruited and
      randomly assigned to either Group or Individual diabetes self-management (DSME).
      Group DSME included story-telling, hands-on activities, and problem-solving
      exercises. Individual DSME sessions focused on goal-setting and problem-solving
      strategies. Sessions were offered in an accessible community center over a 10
      week period. RESULTS: Outcomes included glycosylated hemoglobin (A1C), self-care
      actions, self-efficacy level, goal attainment, and satisfaction with DSME.
      Participants in both Group and Individual DSME improved slightly over the 3-month
      period in self-care activities, A1C level, and goal attainment. Although
      differences were not statistically significant, trends indicate improved scores
      on dietary actions, foot care, goal attainment, and empowerment for those
      experiencing Group DSME. CONCLUSIONS: The culturally tailored approach was well
      received by all participants. Improvements among those receiving Individual DSME
      may indicate that brief sessions usinga culturally tailored approach could
      enhance self-care and glycemic control. Additional testing among more
      participants over a longer time period is recommended.

PMID- 18832291
TI  - Teacher support of adherence for adolescents with type 1 diabetes: preferred
      teacher support behaviors and youths' perceptions of support.
AB  - PURPOSE: The purpose of this study is to examine the preferences of adolescents
      with type 1 diabetes regarding the role of teacher support and perceptions
      associated with the most supportive and least supportive teachers, as well as to
      examine the effects of child age and gender on these relationships. Method This
      cross-sectional questionnaire-based study included 102 adolescents with type 1
      diabetes recruited through the outpatient treatment clinic at a Midwestern
      children's hospital. Adolescents completed demographic questionnaires and
      questionnaires assessing the role of teacher support. Outcome measures included
      the newly developed Ideal Teacher Questionnaire, which measured adolescents'
      preferences for teacher support, and the Diabetes Teacher Support Questionnaire,
      which evaluated adolescents' perceived frequency of teacher support behaviors and
      feelings about this support. RESULTS: Youth rated their most supportive teacher
      as engaging more frequently in support behaviors than their least supportive
      teacher. Students who expressed a preference for an actively involved teacher had
      more positive feelings about the support they received from teachers and
      perceived a higher level of support from their most supportive teacher. Girls
      perceived a greater frequency of support behaviors than boys and felt more
      positive about these behaviors. Younger adolescents reported a higher frequency
      of teacher support behaviors and felt that these behaviors were more supportive.
      CONCLUSIONS: There are consistent interpersonal differences in adolescents'
      desires for teacher support of diabetes self-care. It may be important to
      consider adolescents' preferences for diabetes-related teacher support.

PMID- 18832292
TI  - Characteristics of adolescents with type 1 diabetes who exhibit adverse outcomes.
AB  - PURPOSE: This study seeks to determine differences in key characteristics between
      adolescents with type 1 diabetes who experience the adverse outcomes of poor
      glycemic control, hypoglycemic events, and hospitalizations due to their disease
      versus those who do not experience such events. A secondary purpose is to examine
      differences in outcomes for adolescents using insulin pumps versus daily insulin
      injections (>or=2). METHODS: Data from 108 adolescents were divided according to
      glycemic control (HbA1c <8% vs >or=8%), hypoglycemic reactions and
      hospitalizations in the past year (0 vs >or=1 episode of each), and pump versus
      injection delivery of insulin. Within each grouping, body mass index, insulin
      dose, caloric intake, parental educational level, marital status, annual family
      income, race, and gender were compared. HbA1c level was examined in relation to
      the number of hypoglycemic reactions and hospitalizations in the past year and
      for any differences between those receiving insulin via pump therapy versus daily
      injections (>or=2). RESULTS: Subjects receiving insulin via pump had better
      glucose control and were on lower insulin doses. Subjects with adequate glucose
      control used a lower insulin dose, checked blood glucose levels more frequently,
      and had fathers with a higher education level. Those with inadequate control were
      more likely to come from a single-parent home, a lower-income family, and an
      ethnic minority. CONCLUSIONS: Pump therapy for adolescents should be encouraged
      when appropriate. Also, certain groups of adolescents need increased supervision
      to manage their disease appropriately. Further research needs to explore what
      interventions will bring more favorable outcomes for such groups.

PMID- 18832293
TI  - Bioequivalence studies of tibolone in premenopausal women and effects on
      expression of the tibolone-metabolizing enzyme AKR1C (aldo-keto reductase) family
      caused by estradiol.
AB  - This study aimed to investigate the bioequivalence of a test formulation of
      tibolone with the marketed reference formulation in 24 young healthy female
      volunteers. Tibolone is a synthetic steroid hormone for menopausal women.
      Volunteers were treated with the 2 formulations of tibolone (total dose of active
      ingredient 2.5 mg) according to a 2 x 2 crossover design with a 1-week washout
      period. Plasma concentrations of 3alpha- and 3beta-hydroxytibolone, which are
      major metabolites of tibolone, were assayed in timed samples over a 24-hour
      period with a validated gas chromatography/mass spectrometry (GC/MS) method that
      had a lower limit of quantification of 0.5 ng/mL. The reference and test
      formulations gave a mean 3alpha-hydroxytibolone C(max) of 5.0 and 5.2 ng/mL,
      respectively, and a mean 3beta-hydroxytibolone C(max) of 16.4 and 16.5 ng/mL,
      respectively. The mean AUC(t) of 3alpha-hydroxytibolone was 24.7 and 24.3 ng
      h/mL, whereas the mean AUC(t) of 3beta-hydroxytibolone was 57.6 and 54.8 ng h/mL
      for the test and reference formulations, respectively. The authors did not find
      significant differences in pharmacokinetic parameters between the 2 formulations,
      but metabolite formation was different from reports in postmenopausal women. The
      authors therefore measured the effects of estradiol on the expression of the
      tibolone-metabolizing enzymes, from the aldo-keto reductase (AKR1C) family, using
      HepG2 cell (human hepatoma cells) and MCF-7 cell (human breast cancer cells).
      Estradiol increased mRNA levels of AKR1C1, AKR1C2, and AKR1C3 and protein levels
      of total AKR1C in HepG2 cells. Estradiol selectively enhanced levels of AKR1C2
      mRNA in MCF-7 cells. Thus, changes in the major metabolites of tibolone might
      result from changes in AKR1C family expression by patient estrogen status.

PMID- 18832294
TI  - Pharmacokinetics and safety of ambrisentan in combination with sildenafil in
      healthy volunteers.
AB  - The pharmacokinetic interaction between sildenafil, a phosphodiesterase type 5
      (PDE-5) inhibitor, and ambrisentan, an ET(A)-selective, propanoic acid-based
      endothelin receptor antagonist (ERA), was studied in a 2-period crossover study
      in 19 healthy volunteers, with ambrisentan exposure (AUC(0-infinity)) and maximum
      plasma concentration (C(max)) determined over 24 hours for a 10-mg dose of
      ambrisentan alone and again after 7 days of sildenafil 20 mg 3 times daily. The
      AUC(0-infinity) and C(max) for sildenafil and N-desmethyl sildenafil (active
      metabolite) were determined over 24 hours for a 20-mg dose of sildenafil alone
      and again after 7 days of dosing with ambrisentan 10 mg once daily. There was no
      clinically relevant pharmacokinetic interaction between ambrisentan and
      sildenafil or N-desmethyl sildenafil. Ambrisentan C(max) was unchanged (96.3%
      [90% confidence interval: 86.0%-107.8%]), with a minor increase in AUC(0
      infinity) (108.5% [102.6%-111.7%]) with sildenafil coadministration. Sildenafil
      C(max) was increased slightly (113.4% [99.6%-129.1%]), and AUC(0-infinity) was
      unchanged (98.7% [91.2%-110.5%]) with ambrisentan coadministration. N-desmethyl
      sildenafil was unaltered. Dose adjustment of either drug is not necessary
      compared with administration alone.

PMID- 18832295
TI  - Pharmacokinetics and pharmacodynamics of vildagliptin in healthy Chinese
      volunteers.
AB  - Vildagliptin is an orally effective, potent, and selective inhibitor of
      dipeptidyl peptidase IV (DPP-4) that improves glycemic control in patients with
      type 2 diabetes. This was a randomized, double-blind, placebo-controlled, time
      lagged, parallel-group study in a total of 60 healthy Chinese participants.
      Single- and multiple-dose pharmacokinetics and pharmacodynamics, and safety and
      tolerability of vildagliptin were assessed following administration of 25, 50,
      100, or 200 mg qd, or 50 mg bid. Vildagliptin was rapidly absorbed (tmax 1.5-2.0
      hours) across the dose range of 25 to 200 mg and was quickly eliminated with a
      terminal elimination half-life (t1/2) of approximately 2 hours. Consistent with
      the short t1/2, no accumulation of vildagliptin was observed following the
      administration of multiple doses (accumulation factors were 1.00-1.05 across the
      25- to 200-mg dose range). Vildagliptin AUC and Cmax values increased in an
      approximately dose-proportional fashion (dose proportionality constant beta 1.00
      1.16). Administration of vildagliptin 25 to 200 mg led to rapid and near-complete
      (>95%) inhibition of DPP-4 activity for at least 4 hours after dosing, which was
      associated with increases in plasma active glucagon-like peptide-1 of up to 2- to
      3-fold compared with placebo. The duration of DPP-4 inhibition increased with
      dose. Glucose and insulin levels were not affected by vildagliptin in healthy
      participants, consistent with the fact that the glucose-lowering effects of
      vildagliptin occur in a glucose-dependent fashion. Vildagliptin was well
      tolerated at the highest tested dose of 200 mg qd. Vildagliptin 25 to 200 mg qd
      exhibits approximately dose-proportional pharmacokinetics with no evidence of
      accumulation after multiple dosing in healthy Chinese participants. Vildagliptin
      demonstrates potent inhibition of DPP-4 activity with excellent tolerability at
      doses of up to and including 200 mg qd.

PMID- 18832296
TI  - The chronicles of Porphyromonas gingivalis: the microbium, the human oral
      epithelium and their interplay.
AB  - The microbiota of the human oral mucosa consists of a myriad of bacterial species
      that normally exist in commensal harmony with the host. Porphyromonas gingivalis,
      an aetiological agent in severe forms of periodontitis (a chronic inflammatory
      disease), is a prominent component of the oral microbiome and a successful
      colonizer of the oral epithelium. This Gram-negative anaerobe can also exist
      within the host epithelium without the existence of overt disease. Gingival
      epithelial cells, the outer lining of the gingival mucosa, which function as an
      important part of the innate immune system, are among the first host cells
      colonized by P. gingivalis. This review describes recent studies implicating the
      co-existence and intracellular adaptation of the organism in these target host
      cells. Specifically, recent findings on the putative mechanisms of persistence,
      intercellular dissemination and opportunism are highlighted. These new findings
      may also represent an original and valuable model for mechanistic
      characterization of other successful host-adapted, self-limiting, persistent
      intracellular bacteria in human epithelial tissues.

PMID- 18832297
TI  - The role of the RgpA-Kgp proteinase-adhesin complexes in the adherence of
      Porphyromonas gingivalis to fibroblasts.
AB  - Porphyromonas gingivalis strains W50 and ATCC 33277 were shown to bind to
      cultured human fibroblast (MRC-5) cells using flow cytometry. As the
      concentration of P. gingivalis strain W50 cells was increased relative to the
      concentration of MRC-5 cells, the number of W50 cells bound per MRC-5 cell
      increased, as did the percentage of MRC-5 cells with bacteria bound. However,
      this relationship was only seen for P. gingivalis strain ATCC 33277 at low cell
      concentrations: at high bacterial cell concentrations strain ATCC 33277 auto
      aggregated and binding to the MRC-5 cells decreased. Strain W50 was therefore
      chosen to study the role of the surface proteinase-adhesin complexes (RgpA-Kgp
      complexes) in binding to MRC-5 cells. P. gingivalis W50 cells treated with an
      inhibitor of the RgpA-Kgp complexes exhibited reduced binding to MRC-5 cells. The
      purified active and proteinase-inactive RgpA-Kgp complexes competitively
      inhibited binding of W50 to MRC-5 cells, and isogenic mutants of W50 lacking
      RgpA/B and Kgp displayed reduced binding. P. gingivalis W50 mutant cells lacking
      Kgp exhibited the lowest binding to MRC-5 cells, suggesting an important role for
      this proteinase and its associated adhesins in binding to fibroblasts.

PMID- 18832298
TI  - Identification of TmcN as a pathway-specific positive regulator of tautomycetin
      biosynthesis in Streptomyces sp. CK4412.
AB  - Tautomycetin (TMC) is a novel activated T-cell-specific immunosuppressive
      compound with a unique structure, containing an ester bond linkage between a
      terminal cyclic anhydride moiety and a linear polyketide chain bearing an unusual
      terminal alkene. A 3 kb gene, tmcN, with a deduced product of 1029 amino acid
      residues, located on the 3'-terminus of an approximately 70 kb contiguous TMC
      biosynthetic gene cluster, was found to have amino acid sequence homology with
      bacterial regulatory proteins. In silico database comparisons revealed that TmcN
      belongs to the large ATP-binding regulators of the LuxR protein family. Gene
      disruption of tmcN from the Streptomyces sp. CK4412 chromosome resulted in
      significantly reduced antifungal activity against Aspergillus niger, as well as
      the absence of TMC. In addition, complementation by an integrative plasmid
      carrying tmcN restored TMC biosynthesis, strongly suggesting that TmcN is a
      positive regulator of TMC biosynthesis. Gene expression analysis by RT-PCR of the
      TMC biosynthetic genes revealed that a TmcN mutant strain exhibited reduced
      expression levels for most of the biosynthetic genes except for its own tmcN. It
      is thus suggested that TmcN is a pathway-specific positive regulator that
      activates transcription of the TMC biosynthetic pathway genes in Streptomyces sp.
      CK4412.

PMID- 18832299
TI  - The hrp genes of Pseudomonas cichorii are essential for pathogenicity on eggplant
      but not on lettuce.
AB  - Pseudomonas cichorii causes necrotic lesions in eggplant and rot in lettuce.
      Through transposon insertion into P. cichorii strain SPC9018 we produced two
      mutants, 4-57 and 2-99, that lost virulence on eggplant but not lettuce. Analyses
      showed that a transposon was inserted into the hrpG gene in 4-57 and the hrcT
      gene in 2-99. Nucleotide sequences of the hrp genes of SPC9018 are homologous to
      those of Pseudomonas viridiflava BS group strains. The pathogenicity of 4-57 on
      eggplant was restored by transformation with an hrpF operon, originating from
      either SPC9018 or the BS group member P. viridiflava strain 9504 (Pv9504). These
      data suggested the involvement of hrp genes in the pathogenicity of SPC9018 on
      eggplant, and functional conservation of hrpF operons between SPC9018 and Pv9504.
      Both the hrpS mutant and the hrpL mutant were unable to cause necrotic lesions on
      eggplant leaves but retained their pathogenicity against lettuce. These results
      suggest that the pathogenicity of P. cichorii is hrp-dependent in eggplant, but
      not in lettuce.

PMID- 18832301
TI  - Cyclic di-GMP: a second messenger required for long-term survival, but not for
      biofilm formation, in Mycobacterium smegmatis.
AB  - Cyclic di-GMP (c-di-GMP) plays an important role in bacterial adaptation to
      enable survival in changing environments. It orchestrates various pathways
      involved in biofilm formation, changes in the cell surface, host colonization and
      virulence. In this article, we report the presence of c-di-GMP in Mycobacterium
      smegmatis, and its role in the long-term survival of the organism. M. smegmatis
      has a single bifunctional protein with both GGDEF and EAL domains, which show
      diguanylate cyclase (DGC) and phosphodiesterase (PDE)-A activity, respectively,
      in vitro. We named this protein MSDGC-1. Deletion of the gene encoding MSDGC-1
      did not affect growth and biofilm formation in M. smegmatis, but long-term
      survival under conditions of nutritional starvation was affected. Most of the
      proteins that contain GGDEF and EAL domains have been demonstrated to have either
      DGC or PDE-A activity. To gain further insight into the regulation of the
      protein, we cloned the individual domains, and tested their respective
      activities. MSDGC-1, the full-length protein, is required for activity, as its
      GGDEF and EAL domains are inactive when separated.

PMID- 18832300
TI  - Diversity of IncP-9 plasmids of Pseudomonas.
AB  - IncP-9 plasmids are important vehicles for degradation and resistance genes that
      contribute to the adaptability of Pseudomonas species in a variety of natural
      habitats. The three completely sequenced IncP-9 plasmids, pWW0, pDTG1 and NAH7,
      show extensive homology in replication, partitioning and transfer loci (an
      approximately 25 kb region) and to a lesser extent in the remaining backbone
      segments. We used PCR, DNA sequencing, hybridization and phylogenetic analyses to
      investigate the genetic diversity of 30 IncP-9 plasmids as well as the
      possibility of recombination between plasmids belonging to this family.
      Phylogenetic analysis of rep and oriV sequences revealed nine plasmid subgroups
      with 7-35 % divergence between them. Only one phenotypic character was normally
      associated with each subgroup, except for the IncP-9beta cluster, which included
      naphthalene- and toluene-degradation plasmids. The PCR and hybridization analysis
      using pWW0- and pDTG1-specific primers and probes targeting selected backbone
      loci showed that members of different IncP-9 subgroups have considerable
      similarity in their overall organization, supporting the existence of a conserved
      ancestral IncP-9 sequence. The results suggested that some IncP-9 plasmids are
      the product of recombination between plasmids of different IncP-9 subgroups but
      demonstrated clearly that insertion of degradative transposons has occurred on
      multiple occasions, indicating that association of this phenotype with these
      plasmids is not simply the result of divergent evolution from a single successful
      ancestral degradative plasmid.

PMID- 18832302
TI  - A mathematical model for growth and osmoregulation in halophilic bacteria.
AB  - Many molecular details of the ecophysiology of halophilic bacteria that use
      compatible solutes to maintain osmotic equilibrium have been examined. We ask
      whether the details are consistent and complete enough to predict growth and
      osmoregulation in these bacteria by integrating this information in a
      mathematical model. Parameterized for the halophilic organism Halomonas elongata,
      the model predicts the substrate and salt dependence of growth, the uptake of
      potassium and ectoine and the synthesis of ectoine. It is shown that salt (NaCl)
      dependence of growth can be modelled by substrate inhibition kinetics.
      Osmoregulation is known to involve accumulation of both ectoine and potassium
      glutamate in H. elongata. Using published and newly determined parameters,
      osmoregulatory models using either direct turgor or two-step (turgor and
      potassium) signalling are compared. The results are consistent with a role for
      potassium as a second messenger for hyperosmotic stress. Simulations of osmotic
      upshifts show a transient overregulation of the intracellular solute levels, as
      has been previously observed in experiments. A possible adaptive value of this
      overregulation as 'pre-emptive' behaviour in an environment with frequent dry
      periods leading to steadily increasing osmolarity is proposed. As a result of
      growth parameter estimation, a maximum P : O value of 2 for H. elongata can be
      inferred. In conclusion, the model developed here reproduces essential aspects of
      growth and osmoregulation in halophilic bacteria with a minimal set of
      assumptions.

PMID- 18832303
TI  - Characterization of Streptococcus gordonii prophage PH15: complete genome
      sequence and functional analysis of phage-encoded integrase and endolysin.
AB  - Streptococcus gordonii OMZ1039, isolated from supragingival dental plaque, was
      found to harbour a prophage, PH15, whose excision could be induced by mitomycin
      treatment. Phage PH15 belongs to the Siphoviridae. The complete genome sequence
      of PH15 was determined. The genome was 39 136 bp in size and contained 61 ORFs.
      The genome of PH15 was most similar in the structural module to the temperate
      bacteriophages MM1 and phiNIH1.1 from Streptococcus pneumoniae and Streptococcus
      pyogenes, respectively. In strain OMZ1039, PH15 was found to reside as a prophage
      in the cysteinyl-tRNA gene. A plasmid, harbouring the attP site and the integrase
      gene downstream of a constitutive promoter, was capable of site-specific
      integration into the genomes of different oral streptococcal species. The phage
      endolysin was purified after expression in Escherichia coli and found to inhibit
      growth of all S. gordonii strains tested and several different streptococcal
      species, including the pathogens Streptococcus mutans, S. pyogenes and
      Streptococcus agalactiae.

PMID- 18832304
TI  - The PA4204 gene encodes a periplasmic gluconolactonase (PpgL) which is important
      for fitness of Pseudomonas aeruginosa.
AB  - In Pseudomonas aeruginosa, the PA4204 gene encodes a protein with a signal
      peptide and a COG2706 domain of the type present in 3-carboxy-cis,cis-muconate
      lactonizing enzymes. A molecular model based on the structure of the Escherichia
      coli YbhE phosphogluconate lactonizing enzyme shows that the enzyme has a beta
      propeller ('doughnut') structure and a central active site comprising one
      histidine, one glutamic acid and two arginines. Inactivation of the P. aeruginosa
      PA4204 gene had profound phenotypic effects, resulting in slowly growing small
      colonies which frequently gave rise to larger colonies. The small colonies did
      not produce pyocyanin, produced reduced amounts of N-acylhomoserine lactones, and
      had extremely low levels of 2-alkyl-4-quinolones (AQs), while the larger colonies
      produced pyocyanin and higher amounts of AQs, including the pseudomonas quinolone
      signal (PQS), compared with the wild-type strain. Mutagenesis of His 182 in
      PA4204 resulted in the inability of this protein to restore pyocyanin production
      in the PA4204 isogenic mutant, suggesting that this enzyme may share an active
      site with other lactonizing enzymes. The protein with signal peptide was
      expressed as a His fusion in E. coli and purified. Two forms were observed,
      suggesting that the protein is translocated. The purified enzyme cleaved (S)-5
      oxo-2-tetrahydrofurancarboxylic acid and d-glucono-delta-lactone, demonstrating
      lactonase activity. Decreased expression of the cytoplasmic
      phosphogluconolactonase gene (pgl) was observed in the small-colony mutant, and
      the mutant could not grow in the presence of mannitol or gluconate, suggesting
      functions in the detoxification of a gluconolactone and in sugar metabolism.

PMID- 18832305
TI  - LspA inactivation in Mycobacterium tuberculosis results in attenuation without
      affecting phagosome maturation arrest.
AB  - The success of Mycobacterium tuberculosis depends on its ability to survive
      within host macrophages. Here, M. tuberculosis avoids the acidic, hydrolytically
      competent environment of the phagolysosome by arresting phagosome maturation.
      Having shown previously that a M. tuberculosis mutant deficient in lipoprotein
      signal peptidase (LspA) is strongly attenuated in vivo in a mouse model of
      infection, we now studied putative mechanisms involved in attenuation of the lspA
      : : aph mutant at a cellular level. In this work we investigated the ability of
      the mutant to interfere with two host defence mechanisms, i.e. Toll-like receptor
      (TLR)2-dependent immune response and phagosome maturation. While mycobacterial
      lipoproteins have been reported to trigger a TLR2 signalling pathway critical for
      innate immune responses, we found that growth control of the lspA : : aph mutant
      was independent of TLR2. In addition, the lspA : : aph mutant arrested phagosome
      maturation to an extent similar to that of the wild-type, as measured by
      lysosomal-associated membrane protein 1 (LAMP1) co-localization and
      intraphagosomal pH. These observations demonstrate severe attenuation even in the
      presence of arrested phagosome maturation, and point to a role for the early
      phagosome in growth restriction of the M. tuberculosis lspA mutant.

PMID- 18832306
TI  - Phosphorylation-independent activation of the atypical response regulator NblR.
AB  - Cyanobacteria respond to environmental stress conditions by adjusting their
      photosynthesis machinery. In Synechococcus sp. PCC 7942, phycobilisome
      degradation and other acclimation responses after nutrient or high-light stress
      require activation by the orphan response regulator NblR, a member of the
      OmpR/PhoB family. Although NblR contains a putative phosphorylatable residue
      (Asp57), it lacks other conserved residues required to chelate the Mg(2+)
      necessary for aspartic acid phosphorylation or to transduce the phosphorylation
      signal. In close agreement with these features, NblR was not phosphorylated in
      vitro by the low-molecular-mass phosphate donor acetyl phosphate and mutation of
      Asp57 to Ala had no impact on previously characterized NblR functions in
      Synechococcus. On the other hand, in vitro and in vivo assays show that the
      default state of NblR is monomeric, suggesting that, despite input differences,
      NblR activation could involve the same general mechanism of activation by
      dimerization present in known members of the OmpR/PhoB family. Structural and
      functional data indicate that the receiver domain of NblR shares similarities
      with other phosphorylation-independent response regulators such as FrzS and
      HP1043. To acknowledge the peculiarities of these atypical 'two-component'
      regulators with phosphorylation-independent signal transduction mechanisms, we
      propose the term PIARR, standing for phosphorylation-independent activation of
      response regulator.

PMID- 18832307
TI  - Development of an unambiguous and discriminatory multilocus sequence typing
      scheme for the Streptococcus zooepidemicus group.
AB  - The zoonotic pathogen Streptococcus equi subsp. zooepidemicus (S. zooepidemicus)
      is commonly found harmlessly colonizing the equine nasopharynx. Occasionally,
      strains can invade host tissues or cross species barriers, and S. zooepidemicus
      is associated with numerous different diseases in a variety of hosts, including
      inflammatory airway disease and abortion in horses, pneumonia in dogs and
      meningitis in humans. A biovar of S. zooepidemicus, Streptococcus equi subsp.
      equi, is the causative agent of strangles, one of the most important infections
      of horses worldwide. We report here the development of the first multilocus
      sequence typing (MLST) scheme for S. zooepidemicus and its exploitation to define
      the population genetic structure of these related pathogens. A total of 130
      unique sequence types were identified from 277 isolates of diverse geographical
      and temporal origin. Isolates of S. equi shared a recent evolutionary ancestor
      with isolates of S. zooepidemicus that were significantly associated with cases
      of uterine infection or abortion in horses (P<0.001). Isolates of S.
      zooepidemicus from three UK outbreaks of acute fatal haemorrhagic pneumonia in
      dogs during 1999, 2001 and 2008 were found to be related to isolates from three
      outbreaks of this disease in the USA during 2005, 1993 and 2006, respectively.
      Our data provide strong evidence that S. equi evolved from an ancestral S.
      zooepidemicus strain and that certain related strains of S. zooepidemicus have a
      greater propensity to infect particular hosts and tissues.

PMID- 18832308
TI  - Polar secretion of proteins via the Xcp type II secretion system in Pseudomonas
      aeruginosa.
AB  - The subcellular localization of the major type II secretion system of Pseudomonas
      aeruginosa, the Xcp system, was studied microscopically using a biarsenical
      ligand that becomes fluorescent upon binding to a tetracysteine motif (Lumio
      tag), which was fused to several Xcp components. Fusion of the Lumio tag to the C
      termini of the XcpR and XcpS proteins did not affect the functionality of these
      proteins. Fluorescence microscopy showed that they were predominantly localized
      to the poles of P. aeruginosa cells, when produced at levels comparable to
      chromosomally encoded XcpR and XcpS. In most labelled cells, the proteins were
      found at one of the poles, although bipolar localization was also observed. When
      produced in the absence of other Xcp components, labelled XcpS was still found to
      locate at the poles, whereas XcpR was evenly distributed in the cell. These data
      suggest that XcpS, but not XcpR, contains information required for polar
      localization. The polar location of the Xcp machinery was further confirmed by
      the visualization of protease secretion with an intramolecularly quenched casein
      conjugate.

PMID- 18832309
TI  - Interaction of Mycoplasma genitalium with host cells: evidence for nuclear
      localization.
AB  - Mycoplasma genitalium (Mg) is a mollicute that causes a range of human urogenital
      infections. A hallmark of these bacteria is their ability to establish chronic
      infections that can persist despite completion of appropriate antibiotic
      therapies and intact and functional immune systems. Intimate adherence and
      surface colonization of mycoplasmas to host cells are important pathogenic
      features. However, their facultative intracellular nature is poorly understood,
      partly due to difficulties in developing and standardizing cellular interaction
      model systems. Here, we characterize growth and invasion properties of two Mg
      strains (G37 and 1019V). Mg G37 is a high-passage laboratory strain, while Mg
      1019V is a low-passage isolate recovered from the cervix. The two strains diverge
      partially in gene sequences for adherence-related proteins and exhibit subtle
      variations in their axenic growth. However, with both strains and consistent with
      our previous studies, a subset of adherent Mg organisms invade host cells and
      exhibit perinuclear targeting. Remarkably, intranuclear localization of Mg
      proteins is observed, which occurred as early as 30 min after infection. Mg
      strains deficient in adherence were markedly reduced in their ability to invade
      and associate with perinuclear and nuclear sites.

PMID- 18832310
TI  - Division protein interaction web: identification of a phylogenetically conserved
      common interactome between Streptococcus pneumoniae and Escherichia coli.
AB  - The ability of each of the 11 Streptococcus pneumoniae division proteins to
      interact with itself and with each of the remaining proteins was studied in 66
      combinations of protein pairs, using a bacterial two-hybrid system. Interactions
      (homo- or hetero-dimerizations) were detected between 37 protein pairs, whereas
      29 protein pairs did not interact. In some cases, positive interactions of the S.
      pneumoniae proteins were confirmed by co-immunoprecipitation experiments in
      Escherichia coli. Comparison between the S. pneumoniae division protein
      interaction web and that of E. coli, the only micro-organisms for which the whole
      division interactome has been described systematically, was also performed. At
      least nine division proteins, ZapA, FtsZ, FtsA, FtsK, FtsQ/DivIB, FtsB/DivIC,
      FtsL, FtsI and FtsW, are believed to have a conserved function between these
      bacteria and thus we may say that a significant part of the interactions are
      conserved. Out of 45 protein pairs tested in both bacteria, 30 showed the same
      behaviour: 23 interacted while seven did not. In agreement with these results,
      cross-interactions between S. pneumoniae proteins and the corresponding E. coli
      orthologues were observed. Taken together, these results suggest a
      phylogenetically conserved minimal common interactome of the division proteins.

PMID- 18832311
TI  - Nitrate-responsive NarX-NarL represses arginine-mediated induction of the
      Pseudomonas aeruginosa arginine fermentation arcDABC operon.
AB  - Denitrification and arginine fermentation are major parts of the anaerobic
      metabolism of Pseudomonas aeruginosa, which is important for biofilm formation
      and infection. The two-component regulatory system NarX-NarL is part of the
      underlying network and is required for denitrifying growth. All target promoters
      identified so far are activated by NarL. In this study the effect of NarL on
      arginine fermentation was investigated using proteome, Northern blot and lacZ
      reporter gene analyses. NarL-dependent repression of the arcDABC operon was
      observed and the corresponding NarL-binding site in the arcD promoter region was
      functionally localized at -60 bp upstream of the transcriptional start site using
      site-directed promoter mutagenesis and reporter gene fusion experiments. The
      results clearly show that in the presence of nitrate NarL represses the arginine
      dependent activation of the arcDABC operon mediated by ArgR. It does not
      influence the oxygen-tension-dependent activation via Anr. Thus, the anaerobic
      energy metabolism of P. aeruginosa is coordinated via NarX-NarL activity. In the
      presence of nitrate the highly efficient denitrification is preferred over the
      less attractive arginine fermentation.

PMID- 18832312
TI  - The activity of the glyoxylate cycle in peroxisomes of Candida albicans depends
      on a functional beta-oxidation pathway: evidence for reduced metabolite transport
      across the peroxisomal membrane.
AB  - The glyoxylate cycle, a metabolic pathway required for generating C(4) units from
      C(2) compounds, is an important factor in virulence, in both animal and plant
      pathogens. Here, we report the localization of the key enzymes of this cycle,
      isocitrate lyase (Icl1; EC 4.1.3.1) and malate synthase (Mls1; EC 2.3.3.9), in
      the human fungal pathogen Candida albicans. Immunocytochemistry in combination
      with subcellular fractionation showed that both Icl1 and Mls1 are localized to
      peroxisomes, independent of the carbon source used. Although Icl1 and Mls1 lack a
      consensus type I peroxisomal targeting signal (PTS1), their import into
      peroxisomes was dependent on the PTS1 receptor Pex5p, suggesting the presence of
      non-canonical targeting signals in both proteins. Peroxisomal
      compartmentalization of the glyoxylate cycle is not essential for proper
      functioning of this metabolic pathway because a pex5Delta/Delta strain, in which
      Icl1 and Mls1 were localized to the cytosol, grew equally as well as the wild
      type strain on acetate and ethanol. Previously, we reported that a
      fox2Delta/Delta strain that is completely deficient in fatty acid beta-oxidation,
      but has no peroxisomal protein import defect, displayed strongly reduced growth
      on non-fermentable carbon sources such as acetate and ethanol. Here, we show that
      growth of the fox2Delta/Delta strain on these carbon compounds can be restored
      when Icl1 and Mls1 are relocated to the cytosol by deleting the PEX5 gene. We
      hypothesize that the fox2Delta/Delta strain is disturbed in the transport of
      glyoxylate cycle products and/or acetyl-CoA across the peroxisomal membrane and
      discuss the possible relationship between such a transport defect and the
      presence of giant peroxisomes in the fox2Delta/Delta mutant.

PMID- 18832313
TI  - Effect of carbon source availability and growth phase on expression of
      Corynebacterium glutamicum genes involved in the tricarboxylic acid cycle and
      glyoxylate bypass.
AB  - The effect of different carbon sources on the expression of tricarboxylic acid
      (TCA) cycle genes, along with glyoxylate bypass genes, in Corynebacterium
      glutamicum was determined. All TCA cycle genes were coordinately expressed in
      medium containing acetate. Growth in the presence of acetate gave rise to
      abundant expression of most TCA cycle genes, with the level of gltA transcript
      being the highest. However, when the cells entered the stationary phase triggered
      by acetate exhaustion, all genes were repressed, except sucCD and mdhB, which
      were slightly induced. Acetate withdrawal from the growth medium during the
      exponential phase also led to rapid repression of most TCA cycle genes and a
      corresponding twofold increase in the expression of sucCD, which were strongly
      induced by citrate and succinate. In addition, glucose depletion during the
      stationary phase led to a corresponding 8-20-fold induction of the sucCD, aceA
      and aceB genes. Addition of glucose to acetate medium resulted in about 10-fold
      induction of sucCD. The strong dependence of TCA cycle sucCD and glyoxylate
      bypass aceA and aceB expression on carbon source availability was confirmed and
      the regulatory system will be studied precisely.

PMID- 18832314
TI  - Analysis of the pSK1 replicon, a prototype from the staphylococcal
      multiresistance plasmid family.
AB  - Multidrug-resistant staphylococci often harbour plasmids that carry genes
      conferring resistance to several antimicrobial compounds. Many of these
      multiresistance plasmids appear to utilize a related theta-type replication
      system for which multiresistance plasmid pSK1 serves as a prototype. Essential
      pSK1 replication elements were identified by cloning segments of the replication
      region and testing the resulting plasmids for replication proficiency. An
      iterated region within rep and a DNA segment of up to 68 bp upstream of the rep
      promoter were both found to be essential for origin activity. The Rep protein was
      overexpressed as a 6xHis-tagged C-terminal fusion protein and was shown to bind
      in vitro to four Rep boxes located within the rep coding region. Inactivation of
      a divergently oriented promoter upstream of rep, designated P(rnaI), resulted in
      an elevated plasmid copy number. Comparative analyses suggest that the
      replication systems of many staphylococcal multiresistance plasmids share a
      similar genetic organization and utilize an antisense-RNA-mediated regulatory
      mechanism for copy number control.

PMID- 18832315
TI  - Aromatic degradative pathways in Acinetobacter baylyi underlie carbon catabolite
      repression.
AB  - Carbon catabolite repression is an important mechanism allowing efficient carbon
      source utilization. In the soil bacterium Acinetobacter baylyi, this mechanism
      has been shown to apply to the aromatic degradative pathways for the substrates
      protocatechuate, p-hydroxybenzoate and vanillate. In this investigation,
      transcriptional fusions with the gene for luciferase in the gene clusters for the
      degradation of benzyl esters, anthranilate, benzoate, hydroxycinnamates and
      dicarboxylates (are, ant, ben, hca and dca genes) were constructed and
      established in the chromosome of A. baylyi. The respective strains revealed the
      presence of strong carbon catabolite repression at the transcriptional level. In
      all cases, succinate and acetate in combination had the strongest repressing
      effect, and pyruvate (or lactate in case of the ben and hca genes) allowed the
      highest expression when these carbon sources were supplied together with the
      respective inducer. The pattern of repression for the different cosubstrates was
      similar for all operons investigated and was also observed in the absence of the
      respective inducing compounds, indicating a mechanism that is independent of the
      respective specific regulators. Repression by acetate and succinate varied
      between 88 % for the hca genes and 99 % for the pca genes.

PMID- 18832316
TI  - The putrescine analogue 1,4-diamino-2-butanone affects polyamine synthesis,
      transport, ultrastructure and intracellular survival in Leishmania amazonensis.
AB  - Polyamines are important regulators of growth and differentiation in a variety of
      cells, including parasitic protozoa. Promastigotes of Leishmania species have
      high levels of putrescine and spermidine and their growth can be inhibited by
      polyamine biosynthesis antagonists. The putrescine analogue 1,4-diamino-2
      butanone (DAB) is microbicidal against Tritrichomonas foetus and Trypanosoma
      cruzi, so we tested its effects on Leishmania amazonensis proliferation,
      viability, organization, putrescine transport and synthesis as well as in vitro
      infectivity. DAB impaired promastigote proliferation dose-dependently (IC(50) 144
      microM) and the parasite putrescine concentration was reduced by nearly 50 %.
      This analogue markedly inhibited both ornithine decarboxylase activity and
      [H(3)]putrescine uptake by promastigotes. Pre-treatment with DAB for 24 h led to
      compensatory enhancement of putrescine uptake, indicating an adaptive mechanism
      in DAB-treated parasites. Remarkably, DAB caused mitochondrial damage, assessed
      by transmission electron microscopy, and 3 h treatment with 1 mM DAB enhanced
      lipid peroxidation, whereas incubation with 10 mM DAB or for 24 h resulted in
      decreased peroxidation levels in the parasites. This effect was probably due to
      the loss of mitochondrial function, demonstrated by the diminished reduction of 3
      (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), not observed in
      macrophages. Murine macrophages infected with L. amazonensis amastigotes treated
      with DAB had parasite loads significantly (P<0.05) lower than controls,
      presumably due to interference with putrescine uptake and/or synthesis. These
      results suggest that putrescine may be involved in leishmanial survival, possibly
      by maintaining the parasite's mitochondrial function. The use of analogues to
      interfere with polyamine/diamine synthesis and transport may shed light on its
      function in intracellular parasite survival and lead to identification of new
      targets for leishmaniasis chemotherapy.

PMID- 18832317
TI  - Molecular analysis of the diversity of the sulfide : quinone reductase (sqr) gene
      in sediment environments.
AB  - Our newly designed primers were evaluated for the molecular analysis of specific
      groups of the sqr gene encoding sulfide : quinone reductase (SQR) in sediment
      environments. Based on the phylogenetic analysis, we classified the sqr sequences
      into six groups. PCR primers specific for each group were developed. We
      successfully amplified sqr-like gene sequences related to groups 1, 2 and 4 from
      diverse sediments including a marine sediment (SW), a tidal flat (TS), a river
      sediment (RS) and a lake sediment (FW). We recovered a total of 82 unique
      phylotypes (based on a 95 % amino acid sequence similarity cutoff) from 243
      individual sqr-like gene sequences. Phylotype richness varied widely among the
      groups of sqr-like gene sequences (group 1>group 2>group 4) and sediments
      (SW>TS>RS>FW). Most of the sqr-like gene sequences were affiliated with the
      Proteobacteria clade and were distantly related to the reference sqr gene
      sequences from cultivated strains (less than approximately 80 % amino acid
      sequence similarity). Unique sqr-like gene sequences were associated with
      individual sediment samples in groups 1 and 2. This molecular tool has also
      enabled us to detect sqr-like genes in a sulfur-oxidizing enrichment from marine
      sediments. Collectively, our results support the presence of previously
      unrecognized sqr gene-containing micro-organisms that play important roles in the
      global biogeochemical cycle of sulfur.

PMID- 18832318
TI  - Forces involved in bacterial adhesion to hydrophilic and hydrophobic surfaces.
AB  - Using a parallel-plate flow chamber, the hydrodynamic shear forces to prevent
      bacterial adhesion (F(prev)) and to detach adhering bacteria (F(det)) were
      evaluated for hydrophilic glass, hydrophobic, dimethyldichlorosilane (DDS)-coated
      glass and six different bacterial strains, in order to test the following three
      hypotheses. 1. A strong hydrodynamic shear force to prevent adhesion relates to a
      strong hydrodynamic shear force to detach an adhering organism. 2. A weak
      hydrodynamic shear force to detach adhering bacteria implies that more bacteria
      will be stimulated to detach by passing an air-liquid interface (an air bubble)
      through the flow chamber. 3. DLVO (Derjaguin, Landau, Verwey, Overbeek)
      interactions determine the characteristic hydrodynamic shear forces to prevent
      adhesion and to detach adhering micro-organisms as well as the detachment induced
      by a passing air-liquid interface. F(prev) varied from 0.03 to 0.70 pN, while
      F(det) varied from 0.31 to over 19.64 pN, suggesting that after initial contact,
      strengthening of the bond occurs. Generally, it was more difficult to detach
      bacteria from DDS-coated glass than from hydrophilic glass, which was confirmed
      by air bubble detachment studies. Calculated attractive forces based on the DLVO
      theory (F(DLVO)) towards the secondary interaction minimum were higher on glass
      than on DDS-coated glass. In general, all three hypotheses had to be rejected,
      showing that it is important to distinguish between forces acting parallel
      (hydrodynamic shear) and perpendicular (DLVO, air-liquid interface passages) to
      the substratum surface.

PMID- 18832319
TI  - The cyanobacterial homologue of the RNA chaperone Hfq is essential for motility
      of Synechocystis sp. PCC 6803.
AB  - The ssr3341 locus was previously suggested to encode an orthologue of the RNA
      chaperone Hfq in the cyanobacterium Synechocystis sp. strain PCC 6803.
      Insertional inactivation of this gene resulted in a mutant that was not naturally
      transformable and exhibited a non-phototactic phenotype compared with the wild
      type. The loss of motility was complemented by reintroduction of the wild-type
      gene, correlated with the re-establishment of type IV pili on the cell surface.
      Microarray analyses revealed a small set of genes with drastically reduced
      transcript levels in the knockout mutant compared with the wild-type cells. Among
      the most strongly affected genes, slr1667, slr1668, slr2015, slr2016 and slr2018
      stood out, as they belong to two operons that had previously been shown to be
      involved in motility, controlled by the cAMP receptor protein SYCRP1. This
      suggests a link between cAMP signalling, motility and possibly the involvement of
      RNA-based regulation. This is believed to be the first report demonstrating a
      functional role of an Hfq orthologue in cyanobacteria, establishing a new factor
      in the control of motility.

PMID- 18832320
TI  - Multidrug efflux pump overexpression in Staphylococcus aureus after single and
      multiple in vitro exposures to biocides and dyes.
AB  - Biocides and dyes are commonly employed in hospital and laboratory settings. Many
      of these agents are substrates for multiple-drug resistance (MDR)-conferring
      efflux pumps of both Gram-positive and Gram-negative organisms. Several such
      pumps have been identified in Staphylococcus aureus, and mutants overexpressing
      the NorA and MepA MDR pumps following exposure to fluoroquinolones have been
      identified. The effect of exposure to low concentrations of biocides and dyes on
      the expression of specific pump genes has not been evaluated. Using quantitative
      reverse-transcription PCR we found that exposure of clinical isolates to low
      concentrations of a variety of biocides and dyes in a single step, or to
      gradually increasing concentrations over several days, resulted in the appearance
      of mutants overexpressing mepA, mdeA, norA and norC, with mepA overexpression
      predominating. Overexpression was frequently associated with promoter-region or
      regulatory protein mutations. Mutants having significant increases in MICs of
      common pump substrates but no changes in expression of studied pump genes were
      also observed; in these cases changes in expression of as-yet-unidentified MDR
      pump genes may have occurred. Strains of S. aureus that exist in relatively
      protected environments and are repeatedly exposed to sublethal concentrations of
      biocides can develop efflux-related resistance to those agents, and acquisition
      of such strains poses a threat to patients treated with antimicrobial agents that
      are also substrates for those pumps, such as ciprofloxacin and moxifloxacin.

PMID- 18832321
TI  - Genetic prerequisites for additive or synergistic actions of 5-fluorocytosine and
      fluconazole in baker's yeast.
AB  - During applications of 5-fluorocytosine (5FC) and fluconazole (FLC), additive or
      synergistic action may even occur when primary resistance to 5FC is established.
      Here, we analysed conjoint drug action in Saccharomyces cerevisiae strains
      deficient in genes known to be essential for 5FC or FLC function. Despite clear
      primary resistance, residual 5FC activity and additive 5FC+FLC action in cells
      lacking cytosine permease (Fcy2p) or uracil phosphoribosyl transferase (Fur1p)
      were detected. In contrast, Deltafcy1 mutants, lacking cytosine deaminase, became
      entirely resistant to 5FC, concomitantly losing 5FC+FLC additivity. Disruption of
      the orotate phosphoribosyltransferase gene (URA5) in the wild-type led to low
      level 5FC tolerance, while an alternative orotate phosphoribosyltransferase,
      encoded by URA10, contributed to 5FC toxicity only in the Deltaura5 background.
      Remarkably, combination of Deltaura5 and Deltafur1 resulted in complete 5FC
      resistance. Thus, yeast orotate phosphoribosyltransferases are involved in 5FC
      metabolism. Similarly, disruption of the ergosterol Delta(5,6)-desaturase
      encoding gene ERG3 resulted only in partial resistance to FLC, and concomitantly
      a synergistic effect with 5FC became evident. Full resistance to FLC occurred in
      Deltaerg3 Deltaerg11 double mutants and, simultaneously, synergism or even an
      additive effect with FLC and 5FC was no longer discernible. Since the majority of
      spontaneously occurring resistant yeast clones displayed residual sensitivity to
      either 5FC or FLC and those strains responded to combined drug treatment in a
      predictable manner, careful resistance profiling based on the findings reported
      here may help to address yeast infections by combined application of antimycotic
      compounds.

PMID- 18832322
TI  - Identification and use of the putative Bacteroides ovatus xylanase promoter for
      the inducible production of recombinant human proteins.
AB  - The use of genetically modified bacteria to deliver biologically active molecules
      directly to the gut has become an increasingly attractive area of investigation.
      The challenge of regulation of production of the therapeutic molecule and
      colonization of the bowel led us to investigate Bacteroides ovatus for the
      production of these molecules, due to its ability to colonize the colon and xylan
      utilization properties. Here we have identified the putative xylanase promoter.
      The 5' region of the corresponding mRNA was determined by 5'RACE analysis and the
      transcription initiation site was identified 216 bp upstream of the ATG start
      codon. The putative xylanase promoter was regulated by xylan in a dose- and time
      dependent manner, and repressed by glucose. This promoter was subsequently used
      to direct the controlled expression of a gene encoding the human intestinal
      trefoil factor (TFF-3) after integration as a single copy into the chromosome of
      B. ovatus. The resulting strain produced biologically active TFF-3 in the
      presence of xylan. These findings identify the B. ovatus xylanase operon promoter
      and show that it can be utilized to direct xylan-inducible expression of
      heterologous eukaryotic genes in B. ovatus.

PMID- 18832323
TI  - Detection of small RNAs in Pseudomonas aeruginosa by RNomics and structure-based
      bioinformatic tools.
AB  - Inactivation of the Pseudomonas aeruginosa (PAO1) hfq gene, encoding the Sm-like
      Hfq protein, resulted in pleiotropic effects that included an attenuated
      virulence. As regulation by Hfq often involves the action of small regulatory
      RNAs (sRNAs), we have used a shotgun cloning approach (RNomics) and bioinformatic
      tools to identify sRNAs in strain PAO1. For cDNA library construction, total RNA
      was extracted from PAO1 cultures either grown to stationary phase or exposed to
      human serum. The cDNA libraries were generated from small-sized RNAs of PAO1
      after co-immunoprecipitation with Hfq. Of 400 sequenced cDNA clones, 11 mapped to
      intergenic regions. Band-shift assays and Northern blot analyses performed with
      two selected sRNAs confirmed that Hfq binds to and affects the steady-state
      levels of these RNAs. A proteome study performed upon overproduction of one sRNA,
      PhrS, implicated it in riboregulation. PhrS contains an ORF, and evidence for its
      translation is presented. In addition, based on surveys with structure-based
      bioinformatic tools, we provide an electronic compilation of putative sRNA and
      non-coding RNA genes of PAO1 based on their evolutionarily conserved structure.

PMID- 18832324
TI  - Role of Mycoplasma genitalium MG218 and MG317 cytoskeletal proteins in terminal
      organelle organization, gliding motility and cytadherence.
AB  - The terminal organelle is a differentiated structure that plays a key role in
      mycoplasma cytadherence and locomotion. For this reason, the analysis of
      Mycoplasma genitalium mutants displaying anomalous terminal organelles could
      improve our knowledge regarding the structural elements required for proper
      locomotion. In this study, we isolated several M. genitalium mutants having
      transposon insertions within the mg218 or mg317 genes, which encode the
      orthologues of Mycoplasma pneumoniae HMW2 and HMW3 cytoskeletal proteins,
      respectively. As expected, mg218(-) and mg317(-) mutants exhibit a reduced
      gliding motility, although their ability to attach to solid surfaces was not
      completely abolished. Interestingly, most of the mg218(-) mutants expressed N
      terminal MG218 derivatives and showed the presence of short terminal organelles
      retaining many of the functions displayed by this structure in the wild-type
      strain, suggesting that the N-terminal region of this protein is an essential
      element in the architecture of the terminal organelle. Separately, the analysis
      of mg317(-) mutants indicates that MG317 protein is involved in the formation of
      the terminal button and contributes to anchoring the electron-dense core to the
      cell membrane. The results presented here clearly show that MG218 and MG317
      proteins are implicated in the maintenance of gliding motility and cytadherence
      in M. genitalium.

PMID- 18832326
TI  - Expression of two distinct types of pili by a hospital-acquired Enterococcus
      faecium isolate.
AB  - Surface filamentous structures designated pili, and implicated in virulence, have
      been found on the surfaces of several Gram-positive pathogens. This work
      describes the conditional expression of two phenotypically distinct pilus-like
      structures, designated PilA and PilB, on the surface of a hospital-adapted
      Enterococcus faecium bloodstream isolate. E. faecium is an emerging Gram-positive
      opportunistic pathogen that can cause severe disease, particularly in
      immunocompromised patients. Expression of PilA- and PilB-type pili was analysed
      during different phases of growth in broth culture. During growth, PilA and PilB
      pilin subunits were expressed around the cross-wall in early-exponential-phase
      cells. Polymerization and migration of short PilB-type pili towards the poles
      occurred in cells from the exponential phase and long polymerized pili were
      expressed at the poles of cells grown to stationary phase. In contrast, PilA-type
      pili were not expressed in broth culture, but only when cells were grown on solid
      media. Furthermore, surface expression of the PilA- and PilB-type pili was
      regulated in a temperature-dependent manner, as polymerization of two distinct
      types of pili at the surface only occurred when cells were grown at 37 degrees C;
      no pili were observed on cells grown at 21 degrees C. Hospital-aquired E. faecium
      isolates were specifically enriched in pilin gene clusters, suggesting that
      conditional expression of pili may contribute to E. faecium pathogenesis.

PMID- 18832325
TI  - Identification and phenotypic characterization of a second collagen adhesin, Scm,
      and genome-based identification and analysis of 13 other predicted MSCRAMMs,
      including four distinct pilus loci, in Enterococcus faecium.
AB  - Attention has recently been drawn to Enterococcus faecium because of an
      increasing number of nosocomial infections caused by this species and its
      resistance to multiple antibacterial agents. However, relatively little is known
      about the pathogenic determinants of this organism. We have previously identified
      a cell-wall-anchored collagen adhesin, Acm, produced by some isolates of E.
      faecium, and a secreted antigen, SagA, exhibiting broad-spectrum binding to
      extracellular matrix proteins. Here, we analysed the draft genome of strain
      TX0016 for potential microbial surface components recognizing adhesive matrix
      molecules (MSCRAMMs). Genome-based bioinformatics identified 22 predicted cell
      wall-anchored E. faecium surface proteins (Fms), of which 15 (including Acm) had
      characteristics typical of MSCRAMMs, including predicted folding into a modular
      architecture with multiple immunoglobulin-like domains. Functional
      characterization of one [Fms10; redesignated second collagen adhesin of E.
      faecium (Scm)] revealed that recombinant Scm(65) (A- and B-domains) and Scm(36)
      (A-domain) bound to collagen type V efficiently in a concentration-dependent
      manner, bound considerably less to collagen type I and fibrinogen, and differed
      from Acm in their binding specificities to collagen types IV and V. Results from
      far-UV circular dichroism measurements of recombinant Scm(36) and of Acm(37)
      indicated that these proteins were rich in beta-sheets, supporting our folding
      predictions. Whole-cell ELISA and FACS analyses unambiguously demonstrated
      surface expression of Scm in most E. faecium isolates. Strikingly, 11 of the 15
      predicted MSCRAMMs clustered in four loci, each with a class C sortase gene; nine
      of these showed similarity to Enterococcus faecalis Ebp pilus subunits and also
      contained motifs essential for pilus assembly. Antibodies against one of the
      predicted major pilus proteins, Fms9 (redesignated EbpC(fm)), detected a 'ladder'
      pattern of high-molecular-mass protein bands in a Western blot analysis of cell
      surface extracts from E. faecium, suggesting that EbpC(fm) is polymerized into a
      pilus structure. Further analysis of the transcripts of the corresponding gene
      cluster indicated that fms1 (ebpA(fm)), fms5 (ebpB(fm)) and ebpC(fm) are co
      transcribed, a result consistent with those for pilus-encoding gene clusters of
      other Gram-positive bacteria. All 15 genes occurred frequently in 30 clinically
      derived diverse E. faecium isolates tested. The common occurrence of MSCRAMM- and
      pilus-encoding genes and the presence of a second collagen-binding protein may
      have important implications for our understanding of this emerging pathogen.

PMID- 18832327
TI  - Vancomycin heteroresistance and biofilm formation in Staphylococcus epidermidis
      from food.
AB  - Staphylococcus epidermidis CNBL 7032 is a heteroresistant strain, with
      subpopulations resistant to vancomycin concentrations up to 32 mg l (-1), which
      was isolated from cured pork meat. The mechanisms of glycopeptide resistance in
      this strain were investigated in this study. S. epidermidis CNBL 7032 does not
      harbour enterococcal transmissible vancomycin-resistance genes. Transmission
      electron microscopy revealed that resistant subpopulations have a thicker cell
      wall, and that the increase in cell wall thickness is proportional to vancomycin
      concentration in the growth medium. Scanning electron microscopy showed that S.
      epidermidis CNBL 7032 forms a biofilm-like structure when grown in the presence
      of vancomycin. This food isolate harbours the gene atlE, coding for an autolysin
      with an adhesive function, which is involved in the first phase of biofilm
      formation. This study has demonstrated an interaction between atlE expression,
      biofilm formation and glycopeptide antibiotic resistance; transcription analysis
      demonstrated that the expression of atlE increased proportionally with the
      vancomycin concentration in the culture. Insertional inactivation of atlE
      confirmed the role of the AtlE autolysin in biofilm and vancomycin resistance.

PMID- 18832328
TI  - Characterizing the replication and stability regions of Spiroplasma citri
      plasmids identifies a novel replication protein and expands the genetic toolbox
      for plant-pathogenic spiroplasmas.
AB  - Spiroplasma citri strain GII3 contains seven plasmids, pSciA and pSci1-6, that
      share extensive regions of sequence homology and display a mosaic gene
      organization. Plasmid pSci2 comprises 12 coding sequences (CDS), three of which
      encode polypeptides homologous to proteins Soj/ParA, involved in chromosome
      partitioning, and TrsE and Mob/TraG, implicated in the type IV secretion pathway.
      One CDS encodes the adhesin-like protein ScARP3d whereas the other eight encode
      polypeptides with no homology to known proteins. The pSci2 CDS pE and soj have
      counterparts in all seven plasmids. Through successive deletions, various pSci2
      derivatives were constructed and assessed for their ability to replicate by
      transformation of S. citri 44, a strain which has no plasmid. The smallest
      functional replicon was found to contain a single CDS (pE) and its flanking
      intergenic regions. Shuttle (S. citri/Escherichia coli) plasmids, in which CDS pE
      was disrupted, failed to replicate in S. citri, suggesting that PE is the
      replication protein of the S. citri plasmids. Successive propagations of pSci2
      derived transformed spiroplasmas, in the absence of selection pressure, revealed
      that only pSci2 derivatives having an intact soj gene were stably maintained,
      indicating that the soj-encoded polypeptide is most likely involved in plasmid
      partitioning. Upon transformation, pSci2 derivatives, including shuttle (S.
      citri/E. coli) plasmids, were shown to replicate in all S. citri strains tested
      regardless of whether the strain possesses endogenous plasmids, such as strain
      GII3, or not, such as strain R8A2. In addition, the pSci replicons were
      introduced efficiently into the plant-pathogenic spiroplasmas Spiroplasma
      kunkelii and Spiroplasma phoeniceum, the transformation of which had never, to
      our knowledge, been described before. These studies show that, besides their
      implications for the biology of S. citri, the pSci plasmids hold considerable
      promise as vectors of general use for genetic studies of plant-pathogenic
      spiroplasmas. As an example, a HA-tagged S. citri protein was expressed in S.
      kunkelii. Detection of pE-hybridizing sequences in various group I spiroplasma
      species indicated that pE replicating plasmids were not restricted to the three
      plant-pathogenic spiroplasmas.

PMID- 18832329
TI  - Population vector analysis of primate mediodorsal thalamic activity during
      oculomotor delayed-response performance.
AB  - To understand functional roles of the thalamic mediodorsal nucleus (MD) in
      sensory-to-motor information transformation during spatial working memory
      performance and compare with those of the dorsolateral prefrontal cortex (DLPFC),
      we calculated population vectors using a population of MD activities recorded
      during 2 tasks. In the oculomotor delayed-response (ODR) task, monkeys needed to
      make a memory-guided saccade to the cue location, whereas in the rotatory
      oculomotor delayed-response (R-ODR) task, they needed to make a memory-guided
      saccade 90 degrees clockwise from the cue direction. The directions of population
      vectors calculated from populations of cue- and response-period activities were
      similar to the cue and saccade target directions, respectively, which confirmed
      that population vectors represent information regarding the directions of the
      visual cue and the saccade target. We then calculated population vectors of delay
      period activity using a sliding 250-ms time window. In the ODR task, population
      vectors were directed toward the cue direction throughout the delay. However, in
      the R-ODR task, they gradually rotated from the cue direction to the saccade
      target direction. Based on a comparison with the results obtained from DLPFC
      neurons, the rotation of population vectors started earlier in the MD than in the
      DLPFC, suggesting that the motor information regarding forthcoming saccade is
      provided from the MD.

PMID- 18832330
TI  - Limbic epileptogenesis in a mouse model of fragile X syndrome.
AB  - Fragile X syndrome (FXS), caused by silencing of the Fmr1 gene, is the most
      common form of inherited mental retardation. Epilepsy is reported to occur in 20
      25% of individuals with FXS. However, no overall increased excitability has been
      reported in Fmr1 knockout (KO) mice, except for increased sensitivity to auditory
      stimulation. Here, we report that kindling increased the expressions of Fmr1 mRNA
      and protein in the forebrain of wild-type (WT) mice. Kindling development was
      dramatically accelerated in Fmr1 KO mice, and Fmr1 KO mice also displayed
      prolonged electrographic seizures during kindling and more severe mossy fiber
      sprouting after kindling. The accelerated rate of kindling was partially
      repressed by inhibiting N-methyl-D-aspartic acid receptor (NMDAR) with MK-801 or
      mGluR5 receptor with 2-methyl-6-(phenylethynyl)-pyridine (MPEP). The rate of
      kindling development in WT was not effected by MPEP, however, suggesting that
      FMRP normally suppresses epileptogenic signaling downstream of metabolic
      glutamate receptors. Our findings reveal that FMRP plays a critical role in
      suppressing limbic epileptogenesis and predict that the enhanced susceptibility
      of patients with FXS to epilepsy is a direct consequence of the loss of an
      important homeostatic factor that mitigates vulnerability to excessive neuronal
      excitation.

PMID- 18832331
TI  - TMS evidence for smooth pursuit gain control by the frontal eye fields.
AB  - Smooth pursuit eye movements are used to continuously track slowly moving visual
      objects. A peculiar property of the smooth pursuit system is the nonlinear
      increase in sensitivity to changes in target motion with increasing pursuit
      velocities. We investigated the role of the frontal eye fields (FEFs) in this
      dynamic gain control mechanism by application of transcranial magnetic
      stimulation. Subjects were required to pursue a slowly moving visual target whose
      motion consisted of 2 components: a constant velocity component at 4 different
      velocities (0, 8, 16, and 24 deg/s) and a superimposed high-frequency sinusoidal
      oscillation (4 Hz, +/-8 deg/s). Magnetic stimulation of the FEFs reduced not only
      the overall gain of the system, but also the efficacy of the dynamic gain
      control. We thus provide the first direct evidence that the FEF population is
      significantly involved in the nonlinear computation necessary for continuously
      adjusting the feedforward gain of the pursuit system. We discuss this with
      relation to current models of smooth pursuit.

PMID- 18832332
TI  - REM sleep, prefrontal theta, and the consolidation of human emotional memory.
AB  - Both emotion and sleep are independently known to modulate declarative memory.
      Memory can be facilitated by emotion, leading to enhanced consolidation across
      increasing time delays. Sleep also facilitates offline memory processing,
      resulting in superior recall the next day. Here we explore whether rapid eye
      movement (REM) sleep, and aspects of its unique neurophysiology, underlie these
      convergent influences on memory. Using a nap paradigm, we measured the
      consolidation of neutral and negative emotional memories, and the association
      with REM-sleep electrophysiology. Subjects that napped showed a consolidation
      benefit for emotional but not neutral memories. The No-Nap control group showed
      no evidence of a consolidation benefit for either memory type. Within the Nap
      group, the extent of emotional memory facilitation was significantly correlated
      with the amount of REM sleep and also with right-dominant prefrontal theta power
      during REM. Together, these data support the role of REM-sleep neurobiology in
      the consolidation of emotional human memories, findings that have direct
      translational implications for affective psychiatric and mood disorders.

PMID- 18832333
TI  - System A transporter SAT2 mediates replenishment of dendritic glutamate pools
      controlling retrograde signaling by glutamate.
AB  - Glutamate mediates several modes of neurotransmission in the central nervous
      system including recently discovered retrograde signaling from neuronal
      dendrites. We have previously identified the system N transporter SN1 as being
      responsible for glutamine efflux from astroglia and proposed a system A
      transporter (SAT) in subsequent transport of glutamine into neurons for
      neurotransmitter regeneration. Here, we demonstrate that SAT2 expression is
      primarily confined to glutamatergic neurons in many brain regions with SAT2 being
      predominantly targeted to the somatodendritic compartments in these neurons. SAT2
      containing dendrites accumulate high levels of glutamine. Upon electrical
      stimulation in vivo and depolarization in vitro, glutamine is readily converted
      to glutamate in activated dendritic subsegments, suggesting that glutamine
      sustains release of the excitatory neurotransmitter via exocytosis from
      dendrites. The system A inhibitor MeAIB (alpha-methylamino-iso-butyric acid)
      reduces neuronal uptake of glutamine with concomitant reduction in intracellular
      glutamate concentrations, indicating that SAT2-mediated glutamine uptake can be a
      prerequisite for the formation of glutamate. Furthermore, MeAIB inhibited
      retrograde signaling from pyramidal cells in layer 2/3 of the neocortex by
      suppressing inhibitory inputs from fast-spiking interneurons. In summary, we
      demonstrate that SAT2 maintains a key metabolic glutamine/glutamate balance
      underpinning retrograde signaling by dendritic release of the neurotransmitter
      glutamate.

PMID- 18832334
TI  - DCX and PSA-NCAM expression identifies a population of neurons preferentially
      distributed in associative areas of different pallial derivatives and vertebrate
      species.
AB  - In adult rodents, doublecortin (DCX) and polysialylated neural cell adhesion
      molecule (PSA-NCAM) expression is mostly restricted to newly generated neurons.
      These molecules have also been described in prenatally generated cells of the
      piriform cortex and, to a lesser extent, neocortex (NC) of the rat. In addition,
      PSA-NCAM+ cells have been identified in several telencephalic regions of the
      lizard. Here, through immunohistochemistry and 3-dimensional reconstruction, we
      have investigated distribution, morphology, and phenotype of DCX/PSA-NCAM
      expressing cells in the pallium of different mammals and in lizard. In all
      species, a population of nonnewly-generated pallial DCX+/PSA-NCAM+ cells shows
      common morphological and phenotypic characteristics, including expression of Tbr
      1, a transcription factor expressed in pallial projection neurons, and
      preferential distribution in associative areas. In the guinea pig and rabbit,
      DCX+/PSA-NCAM+ elements are also abundant in the NC, particularly in areas
      implicated in nonspatial learning and memory networks. In reptiles, DCX+/PSA
      NCAM+ cells are located in the lateral and medial cortex and dorsal ventricular
      ridge but not in the dorsal cortex. These data support the fact that coexpression
      of DCX+/PSA-NCAM+/Tbr-1+ in the adult brain identifies evolutionary conserved
      cell populations shared by different pallial derivatives including the mammalian
      NC.

PMID- 18832335
TI  - Neuronal correlates of local, lateral, and translaminar inhibition with reference
      to cortical columns.
AB  - In the neocortex, inhibition by gamma-aminobutyric acidergic (GABAergic)
      interneurons is essential for shaping cortical maps, which represent sensory
      signals. For a detailed understanding of the stream of excitation evoked, for
      example, by a sensory stimulus, interneurons must be identified with reference to
      their impact on excitatory neurons located in different laminae of the same
      (home) and surround columns. We analyzed the axonal projection of layer 2/3
      (L2/3) interneurons with reference to geometric landmarks of cortical columns by
      staining neurons in acute slices of rat barrel cortex (P20-P29) and a subsequent
      cluster analysis using morphological parameters that described the spatial
      distribution of axons. The cluster analysis defined 4 main axonal projection
      "types" referred to as 1) "local inhibitors" (including "chandelier neurons"), 2)
      "lateral inhibitors," 3) "translaminar L2/3-to-L4/5 inhibitors," and 4)
      "translaminar L2/3-to-L1 inhibitors." The putative innervation domains
      established by axonal projections of the 4 types of interneurons and the
      dendritic domains of their target excitatory neurons were 1) L2/3 of the home
      column, 2) L2/3 of both the home and neighboring columns, 3) L4 and L5A of the
      home column, and 4) L1 and L2/3 of the home column. The quantitative analysis of
      the axonal projection patterns of an unselected sample of 51 interneurons located
      in L2/3 thus defined anatomical correlates for local, lateral, and translaminar
      inhibition within and between cortical columns.

PMID- 18832336
TI  - Musical training influences linguistic abilities in 8-year-old children: more
      evidence for brain plasticity.
AB  - We conducted a longitudinal study with 32 nonmusician children over 9 months to
      determine 1) whether functional differences between musician and nonmusician
      children reflect specific predispositions for music or result from musical
      training and 2) whether musical training improves nonmusical brain functions such
      as reading and linguistic pitch processing. Event-related brain potentials were
      recorded while 8-year-old children performed tasks designed to test the
      hypothesis that musical training improves pitch processing not only in music but
      also in speech. Following the first testing sessions nonmusician children were
      pseudorandomly assigned to music or to painting training for 6 months and were
      tested again after training using the same tests. After musical (but not
      painting) training, children showed enhanced reading and pitch discrimination
      abilities in speech. Remarkably, 6 months of musical training thus suffices to
      significantly improve behavior and to influence the development of neural
      processes as reflected in specific pattern of brain waves. These results reveal
      positive transfer from music to speech and highlight the influence of musical
      training. Finally, they demonstrate brain plasticity in showing that relatively
      short periods of training have strong consequences on the functional organization
      of the children's brain.

PMID- 18832337
TI  - The other side of we: when outgroup members express common identity.
AB  - Previous research on the common ingroup identity model has focused on how one's
      representations of members of the ingroup and outgroup influence intergroup
      attitudes. Two studies reported here investigated how learning how others,
      ingroup or outgroup members, conceive of the groups within a superordinate
      category affects intergroup bias and willingness to engage in intergroup contact.
      Across both studies, high school students who learned that other ingroup members
      categorized students at both schools within the common identity of "students"
      showed less intergroup bias in evaluations and greater willingness for contact.
      However, consistent with the hypothesized effects of identity threat, when
      participants read that outgroup members saw the groups within the superordinate
      category, they exhibited a relatively negative orientation, except when ingroup
      members also endorsed a superordinate identity (Study 1). This result occurred
      even when the relative status of the groups was manipulated (Study 2).

PMID- 18832338
TI  - The dark side of creativity: biological vulnerability and negative emotions lead
      to greater artistic creativity.
AB  - Historical and empirical data have linked artistic creativity to depression and
      other affective disorders. This study examined how vulnerability to experiencing
      negative affect, measured with biological products, and intense negative emotions
      influenced artistic creativity. The authors assessed participants' baseline
      levels of an adrenal steroid (dehydroepiandrosterone-sulfate, or DHEAS),
      previously linked to depression, as a measure of affective vulnerability. They
      then manipulated emotional responses by randomly assigning participants to
      receive social rejection or social approval or to a nonsocial situation.
      Participants then completed artistic collages, which were later evaluated by
      artists. Results confirmed a person-by-situation interaction. Social rejection
      was associated with greater artistic creativity; however, the interaction between
      affective vulnerability (lower baseline DHEAS) and condition was significant,
      suggesting that situational triggers of negative affect were especially
      influential among those lower in DHEAS, which resulted in the most creative
      products. These data provide evidence of possible biological and social pathways
      to artistic creativity.

PMID- 18832339
TI  - The good and bad of relationships: how social hindrance and social support affect
      relationship feelings in daily life.
AB  - The authors examined the effects of social hindrance and support on negative and
      positive relationship-specific feelings in three daily diary studies. Study 1
      showed that hindrance and support independently predicted positive relationship
      feelings, but only hindrance predicted negative feelings. Study 2 used new
      measures of hindrance and support and showed that hindrance and support
      independently predicted same-day relationship feelings but that the effects of
      hindrance were stronger in magnitude. Study 3 yielded similar findings using the
      new measures of hindrance and support and controlling for morning feeling. These
      asymmetrical crossover effects suggest that bad is only stronger than good when
      it comes to bad outcomes; they also support the distinction between aversive and
      appetitive relational processes.

PMID- 18832340
TI  - How well can the accuracy of comparative protein structure models be predicted?
AB  - Comparative structure models are available for two orders of magnitude more
      protein sequences than are experimentally determined structures. These models,
      however, suffer from two limitations that experimentally determined structures do
      not: They frequently contain significant errors, and their accuracy cannot be
      readily assessed. We have addressed the latter limitation by developing a
      protocol optimized specifically for predicting the Calpha root-mean-squared
      deviation (RMSD) and native overlap (NO3.5A) errors of a model in the absence of
      its native structure. In contrast to most traditional assessment scores that
      merely predict one model is more accurate than others, this approach quantifies
      the error in an absolute sense, thus helping to determine whether or not the
      model is suitable for intended applications. The assessment relies on a model
      specific scoring function constructed by a support vector machine. This
      regression optimizes the weights of up to nine features, including various
      sequence similarity measures and statistical potentials, extracted from a
      tailored training set of models unique to the model being assessed: If possible,
      we use similarly sized models with the same fold; otherwise, we use similarly
      sized models with the same secondary structure composition. This protocol
      predicts the RMSD and NO3.5A errors for a diverse set of 580,317 comparative
      models of 6174 sequences with correlation coefficients (r) of 0.84 and 0.86,
      respectively, to the actual errors. This scoring function achieves the best
      correlation compared to 13 other tested assessment criteria that achieved
      correlations ranging from 0.35 to 0.71.

PMID- 18832341
TI  - Radial extracorporeal shock wave therapy is safe and effective in the treatment
      of chronic recalcitrant plantar fasciitis: results of a confirmatory randomized
      placebo-controlled multicenter study.
AB  - BACKGROUND: Radial extracorporeal shock wave therapy is an effective treatment
      for chronic plantar fasciitis that can be administered to outpatients without
      anesthesia but has not yet been evaluated in controlled trials. HYPOTHESIS: There
      is no difference in effectiveness between radial extracorporeal shock wave
      therapy and placebo in the treatment of chronic plantar fasciitis. STUDY DESIGN:
      Randomized, controlled trial; Level of evidence, 1. METHODS: Three interventions
      of radial extracorporeal shock wave therapy (0.16 mJ/mm(2); 2000 impulses)
      compared with placebo were studied in 245 patients with chronic plantar
      fasciitis. Primary endpoints were changes in visual analog scale composite score
      from baseline to 12 weeks' follow-up, overall success rates, and success rates of
      the single visual analog scale scores (heel pain at first steps in the morning,
      during daily activities, during standardized pressure force). Secondary endpoints
      were single changes in visual analog scale scores, success rates, Roles and
      Maudsley score, SF-36, and patients' and investigators' global judgment of
      effectiveness 12 weeks and 12 months after extracorporeal shock wave therapy.
      RESULTS: Radial extracorporeal shock wave therapy proved significantly superior
      to placebo with a reduction of the visual analog scale composite score of 72.1%
      compared with 44.7% (P = .0220), and an overall success rate of 61.0% compared
      with 42.2% in the placebo group (P = .0020) at 12 weeks. Superiority was even
      more pronounced at 12 months, and all secondary outcome measures supported radial
      extracorporeal shock wave therapy to be significantly superior to placebo (P <
      .025, 1-sided). No relevant side effects were observed. CONCLUSION: Radial
      extracorporeal shock wave therapy significantly improves pain, function, and
      quality of life compared with placebo in patients with recalcitrant plantar
      fasciitis.

PMID- 18832342
TI  - A comparison between a retrograde interference screw, suture button, and combined
      fixation on the tibial side in an all-inside anterior cruciate ligament
      reconstruction: a biomechanical study in a porcine model.
AB  - BACKGROUND: Effective soft tissue graft fixation to the tibial tunnel in all
      inside anterior cruciate ligament reconstructions has been reported to be a
      problem and may lead to retrograde pullout at ultimate load testing. HYPOTHESIS:
      A combined retrograde bioabsorbable screw and cortical-cancellous suture button
      suspension apparatus would gain stiffness from the button and strength from the
      screw, thus providing for a larger pullout ultimate load, yield load, and
      stiffness when compared with either fixation alone in an all-inside anterior
      cruciate ligament reconstruction. STUDY DESIGN: Controlled laboratory study.
      METHODS: Eighteen porcine tibias (average bone mineral density of 1.46, measured
      by dual-energy x-ray absorptiometry scan) and 18 bovine extensor tendon
      allografts were divided into 3 groups: retrograde bioabsorbable screw fixation,
      cortical-cancellous suture button suspension apparatus fixation, and combined
      fixation in the tibia, with 6 specimens per group. They were biomechanically
      tested with cyclic (500 cycles, 50-250 N, 1 Hz) and load-to-failure (20 mm/min)
      parameters. RESULTS: During cyclic testing, the retrograde screw-only group had a
      larger cyclic displacement (2.98 +/- 2.28 mm) than the suture button with
      retrograde screw combination group (1.40 +/- 0.34 mm). The combination fixation
      group also produced a higher cyclic stiffness (161.93 +/- 61.81 N/mm) than the
      retrograde screw-only group (91.59 +/- 43.26 N/mm). In load-to-failure testing,
      the retrograde screw with suture button combination group withstood significantly
      higher initial failure forces (873.87 +/- 148.74 N) than the retrograde screw
      only (558.44 +/- 126.33 N) and suture button-only (121.76 +/- 40.57 N) groups.
      Additionally, ultimate loads were also significantly higher for the combination
      group (1027 +/- 157.11 N) than either the retrograde screw group (679.00 +/-
      109.44 N) or the suture button group (161.00 +/- 29.27 N). The retrograde screw
      with suture button combination group showed significantly higher pullout
      stiffness (152.50 +/- 46.37 N/mm) than either the retrograde screw-only group
      (78.31 +/- 12.85 N/mm) or the suture button-only group (25.79 +/- 9.30 N/mm).
      CONCLUSION: Soft tissue grafts fixed with a combination of a retrograde screw and
      a suture button were able to withstand higher initial failure and ultimate
      failure loads and were also stiffer than grafts fixed with either a retrograde
      screw or a suture button alone. CLINICAL RELEVANCE: These findings may prove
      useful in providing additional stability when using an all-inside technique in a
      difficult case, or in a patient with poor bone stock, and may also be useful as
      an alternative to more commonly used tibial tunnel soft tissue fixation
      techniques.

PMID- 18832343
TI  - Differential pharmacological effects of antimuscarinic drugs on heart rate: a
      randomized, placebo-controlled, double-blind, crossover study with tolterodine
      and darifenacin in healthy participants > or = 50 years.
AB  - Antimuscarinics, used commonly to treat overactive bladder, may differ in their
      potential to increase heart rate via effects on cardiac muscarinic M2 receptors.
      This prospective, 3-way crossover, randomized, double-blind study assessed the
      heart rate effects of 7 days' exposure to a nonselective M2/M3 receptor blocker
      (tolterodine; 4 mg/d), a highly selective M3 receptor blocker (darifenacin; 15
      mg/d), and placebo in 162 healthy participants > or = 50 years. Heart rate was
      measured by 24-hour Holter monitoring. Tolterodine significantly increased heart
      rate versus darifenacin and heart rate versus placebo, while darifenacin did not
      affect heart rate versus placebo. The proportion of participants with an increase
      in mean heart rate per 24 hours of > or =5 beats per minute was higher with
      tolterodine than with darifenacin (P = .0004) or with placebo (P = .0114) but did
      not differ between darifenacin and placebo. The results show that antimuscarinics
      exert differential effects on heart rate depending on their muscarinic receptor
      profile. This should be considered when selecting a treatment.

PMID- 18832344
TI  - Association between prenatal exposure to bacterial infection and risk of
      schizophrenia.
AB  - Recent research suggests that prenatal exposure to nonviral infection may be
      associated with increased risk of schizophrenia, and we hypothesized an
      association between maternal bacterial infection during pregnancy and elevated
      offspring risk of schizophrenia. Data on maternal infections from the Copenhagen
      Perinatal Cohort were linked with the Danish National Psychiatric Register.
      Offspring cases of narrowly defined schizophrenia (International Classification
      of Diseases, Eighth Revision [ICD-8]) and more broadly defined schizophrenia (ICD
      8 and ICD-10) were identified before the ages of 32-34 and 45-47 years,
      respectively. The effect of prenatal exposure to bacterial infections was
      adjusted for prenatal exposure to analgesics and parental social status. In a
      risk set of 7941 individuals, 85 cases (1.1%) of ICD-8 schizophrenia were
      identified by the age of 32-34 years and 153 cases (1.9%) of more broadly defined
      schizophrenia by the age of 45-47 years. First-trimester exposure conferred an
      elevated risk of ICD-8 schizophrenia (odds ratio 2.53; 95% confidence interval
      [CI] 1.07-5.96) and also of broadly defined schizophrenia (odds ratio 2.14; 95%
      CI 1.06-4.31). Second-trimester exposure also conferred a significantly elevated
      risk of schizophrenia but only in unadjusted analyses. These findings suggest a
      relationship between maternal bacterial infection in pregnancy and offspring risk
      of schizophrenia, and this effect was somewhat stronger for ICD-8 schizophrenia
      with earlier onset. Post hoc analyses showed that upper respiratory tract and
      gonococcal infections were associated with elevated risk of the disease. An
      association between risk of schizophrenia and prenatal exposure to bacterial
      infections might be mediated through transplacental passage of maternally
      produced cytokines in response to bacterial infections.

PMID- 18832345
TI  - Lipid profiling of FPLC-separated lipoprotein fractions by electrospray
      ionization tandem mass spectrometry.
AB  - Glycerophospholipid and sphingolipid species and their bioactive metabolites are
      important regulators of lipoprotein and cell function. The aim of the study was
      to develop a method for lipid species profiling of separated lipoprotein classes.
      Human serum lipoproteins VLDL, LDL, and HDL of 21 healthy fasting blood donors
      were separated by fast performance liquid chromatography (FPLC) from 50 microl
      serum. Subsequently, phosphatidylcholine (PC), lysophosphatidylcholine,
      sphingomyelin (SM), ceramide (CER), phosphatidylethanolamine (PE), PE-based
      plasmalogen (PE-pl), cholesterol, and cholesteryl ester (CE) content of the
      separated lipoproteins was quantified by electrospray ionization tandem mass
      spectrometry (ESI-MS/MS). Analysis of FPLC fractions with PAGE demonstrated that
      albumin partially coelutes with HDL fractions. However, analysis of an HDL
      deficient serum (Tangier disease) showed that only lysophosphatidylcholine, but
      none of the other lipids analyzed, exhibited a significant coelution with the
      albumin containing fractions. Approximately 60% of lipoprotein CER were found in
      LDL fractions and 60% of PC, PE, and plasmalogens in HDL fractions. VLDL, LDL,
      and HDL displayed characteristic lipid class and species pattern. The developed
      method provides a detailed lipid class and species composition of lipoprotein
      fractions and may serve as a valuable tool to identify alterations of lipoprotein
      lipid species profiles in disease with a reasonable experimental effort.

PMID- 18832346
TI  - Occupational risk associated with Toscana virus infection in Tuscany, Italy.
AB  - BACKGROUND: Sandfly fever virus serotype Toscana is endemic in Mediterranean
      countries and is a widespread public health problem as it may be associated with
      acute neurological diseases such as aseptic meningitis. AIM: To assess whether
      Toscana virus infection is associated with occupational exposure. METHODS: During
      the summer of 2001, a total of 678 blood samples were taken from healthy subjects
      residing in Tuscany (349 agricultural and forestry workers and 329 control
      subjects living in the same areas). Information on age, type of job and lifestyle
      was collected in a questionnaire, and sera were analysed using enzyme-linked
      immunosorbent assay for Toscana virus-specific antibodies. RESULTS:
      Seropositivity to antibodies to Toscana virus was 30% in the control group and
      23% in the agricultural and forestry workers (P<0.05). Questionnaire responses
      suggested that, although the agricultural and forestry workers had a potentially
      greater continuous exposure to sandfly fever virus (outdoor activities, rural
      residence and at-risk lifestyle), these risk factors did not add significant
      information about greater susceptibility to disease. CONCLUSION: Our findings
      indicate a need for better understanding of the best preventive measures to avoid
      the risk related to sandfly bites, especially for people who live or work in
      areas at risk.

PMID- 18832347
TI  - Sodium metabisulphite induced airways disease in the fishing and fish-processing
      industry.
AB  - BACKGROUND: Sodium metabisulphite (SMBS) is recognized as a potential cause of
      airway irritation and possibly occupational asthma, but awareness of its use in
      the fishing and fish-processing industry is low. AIMS AND METHODS: To describe
      three cases of occupational airways disease due to SMBS exposure and to review
      the literature. RESULTS: Three patients, one trawlerman and two prawn processors,
      developed work-related airways disease due to exposure to SMBS, one with irritant
      induced asthma with a positive-specific bronchial challenge associated with very
      high sulphur dioxide exposures, one with occupational asthma and one with vocal
      cord dysfunction and underlying asthma. Of the nine cases recorded in the
      literature, most were non-atopic and responses to specific bronchial challenge
      when undertaken showed an immediate response. Exposures to sulphur dioxide in
      these settings are very high, in excess of 30 ppm. CONCLUSION: SMBS should be
      regarded as a cause of occupational airways disease and its use in the fish and
      prawn-processing industry investigated further to better identify risks from
      exposure and handling of the agent in the workplace.

PMID- 18832348
TI  - Recruitment of Saccharomyces cerevisiae Dnl4-Lif1 complex to a double-strand
      break requires interactions with Yku80 and the Xrs2 FHA domain.
AB  - Nonhomologous end joining (NHEJ) in yeast depends on eight different proteins in
      at least three different functional complexes: Yku70-Yku80 (Ku), Dnl4-Lif1-Nej1
      (DNA ligase IV), and Mre11-Rad50-Xrs2 (MRX). Interactions between these complexes
      at DNA double-strand breaks (DSBs) are poorly understood but critical for the
      completion of repair. We previously identified two such contacts that are
      redundantly required for NHEJ, one between Dnl4 and the C terminus of Yku80 and
      one between the forkhead-associated (FHA) domain of Xrs2 and the C terminus of
      Lif1. Here, we first show that mutation of the Yku80 C terminus did not impair Ku
      binding to DSBs, supporting specificity of the mutant defect to the ligase
      interaction. We next show that the Xrs2-Lif1 interaction depends on Xrs2 FHA
      residues (R32, S47, R48, and K75) analogous to those known in other proteins to
      contact phosphorylated threonines. Two potential target threonines in Lif1 (T417
      and T387) were inferred by identifying regions similar to a site in the human
      Lif1 homolog, XRCC4, known to be bound by the FHA domain of polynucleotide
      kinase. Mutating these threonines, especially T417, abolished the Xrs2-Lif1
      interaction and impaired NHEJ epistatically with Xrs2 FHA mutation. Combining
      mutations that selectively disable the Yku80-Dnl4 and Xrs2-Lif1 interactions
      abrogated both NHEJ and DNA ligase IV recruitment to a DSB. The collected results
      indicate that the Xrs-Lif1 and Yku80-Dnl4 interactions are important for
      formation of a productive ligase-DSB intermediate.

PMID- 18832349
TI  - The spindle positioning protein Kar9p interacts with the sumoylation machinery in
      Saccharomyces cerevisiae.
AB  - Accurate positioning of the mitotic spindle is important for the genetic material
      to be distributed evenly in dividing cells, but little is known about the
      mechanisms that regulate this process. Here we report that two microtubule
      associated proteins important for spindle positioning interact with several
      proteins in the sumoylation pathway. By two-hybrid analysis, Kar9p and Bim1p
      interact with the yeast SUMO Smt3p, the E2 enzyme Ubc9p, an E3 Nfi1p, as well as
      Wss1p, a weak suppressor of a temperature-sensitive smt3 allele. The physical
      interaction between Kar9p and Ubc9p was confirmed by in vitro binding assays. A
      single-amino-acid substitution in Kar9p, L304P disrupted its two-hybrid
      interaction with proteins in the sumoylation pathway, but retained its
      interactions with the spindle positioning proteins Bim1p, Stu2p, Bik1p, and
      Myo2p. The kar9-L304P mutant showed defects in positioning the mitotic spindle,
      with the spindle located more distally than normal. Whereas wild-type Kar9p-3GFP
      normally localizes to only the bud-directed spindle pole body (SPB), Kar9p-L304P
      3GFP was mislocalized to both SPBs. Using a reconstitution assay, Kar9p was
      sumoylated in vitro. We propose a model in which sumoylation regulates spindle
      positioning by restricting Kar9p to one SPB. These findings raise the possibility
      that sumoylation could regulate other microtubule-dependent processes.

PMID- 18832350
TI  - The EGL-4 PKG acts with KIN-29 salt-inducible kinase and protein kinase A to
      regulate chemoreceptor gene expression and sensory behaviors in Caenorhabditis
      elegans.
AB  - The regulation of chemoreceptor (CR) gene expression by environmental signals and
      internal cues may contribute to the modulation of multiple physiological
      processes and behavior in Caenorhabditis elegans. We previously showed that KIN
      29, a homolog of salt-inducible kinase, acts in sensory neurons to regulate the
      expression of a subset of CR genes, as well as sensory behaviors. Here we show
      that the cGMP-dependent protein kinase EGL-4 acts partly in parallel with KIN-29
      to regulate CR gene expression. Sensory inputs inhibit both EGL-4 and KIN-29
      functions, and KIN-29 function is inhibited in turn by cAMP-dependent protein
      kinase (PKA) activation. EGL-4 and KIN-29 regulate CR gene expression by
      antagonizing the gene repression functions of the class II HDAC HDA-4 and the MEF
      2 transcription factor, and KIN-29, EGL-4, and PKA target distinct residues in
      HDA-4 to regulate its function and subcellular localization. While KIN-29 acts
      primarily via MEF-2/HDA-4 to regulate additional sensory signal-regulated
      physiological processes and behaviors, EGL-4 acts via both MEF-2-dependent and 
      independent pathways. Our results suggest that integration of complex sensory
      inputs via multiple signaling pathways allows animals to precisely regulate
      sensory gene expression, thereby appropriately modulating physiology and
      behavior.

PMID- 18832351
TI  - Disruption of Rpn4-induced proteasome expression in Saccharomyces cerevisiae
      reduces cell viability under stressed conditions.
AB  - The proteasome homeostasis in Saccharomyces cerevisiae is regulated by a negative
      feedback circuit in which the transcription activator Rpn4 upregulates the
      proteasome genes and is rapidly degraded by the assembled proteasome. Previous
      studies have shown that rpn4Delta cells are sensitive to a variety of stresses.
      However, the contribution of the loss of Rpn4-induced proteasome expression to
      the rpn4Delta phenotypes remains unclear because Rpn4 controls numerous genes
      other than the proteasome genes. Here we construct a yeast strain in which one of
      the essential proteasome genes, PRE1, is no longer induced by Rpn4. We show that
      the active proteasome level is lower in this strain than in the wild-type
      counterpart. Moreover, we demonstrate that loss of Rpn4-induced proteasome
      expression leads to cell-cycle delay in G2/M and sensitizes cells to various
      stresses. To our knowledge, this is the first report that explicitly reveals the
      physiological function of Rpn4-induced proteasome expression. This study also
      provides a tool for understanding the interactions between proteasome homeostasis
      and other cellular processes.

PMID- 18832352
TI  - The temporal program of chromosome replication: genomewide replication in
      clb5{Delta} Saccharomyces cerevisiae.
AB  - Temporal regulation of origin activation is widely thought to explain the pattern
      of early- and late-replicating domains in the Saccharomyces cerevisiae genome.
      Recently, single-molecule analysis of replication suggested that stochastic
      processes acting on origins with different probabilities of activation could
      generate the observed kinetics of replication without requiring an underlying
      temporal order. To distinguish between these possibilities, we examined a
      clb5Delta strain, where origin firing is largely limited to the first half of S
      phase, to ask whether all origins nonspecifically show decreased firing (as
      expected for disordered firing) or if only some origins ("late" origins) are
      affected. Approximately half the origins in the mutant genome show delayed
      replication while the remainder replicate largely on time. The delayed regions
      can encompass hundreds of kilobases and generally correspond to regions that
      replicate late in wild-type cells. Kinetic analysis of replication in wild-type
      cells reveals broad windows of origin firing for both early and late origins. Our
      results are consistent with a temporal model in which origins can show some
      heterogeneity in both time and probability of origin firing, but clustering of
      temporally like origins nevertheless yields a genome that is organized into
      blocks showing different replication times.

PMID- 18832353
TI  - Selective sweep at a quantitative trait locus in the presence of background
      genetic variation.
AB  - We model selection at a locus affecting a quantitative trait (QTL) in the
      presence of genetic variance due to other loci. The dynamics at the QTL are
      related to the initial genotypic value and to the background genetic variance of
      the trait, assuming that background genetic values are normally distributed,
      under three different forms of selection on the trait. Approximate dynamics are
      derived under the assumption of small mutation effect. For similar strengths of
      selection on the trait (i.e, gradient of directional selection beta) the way
      background variation affects the dynamics at the QTL critically depends on the
      shape of the fitness function. It generally causes the strength of selection on
      the QTL to decrease with time. The resulting neutral heterozygosity pattern
      resembles that of a selective sweep with a constant selection coefficient
      corresponding to the early conditions. The signature of selection may also be
      blurred by mutation and recombination in the later part of the sweep. We also
      study the race between the QTL and its genetic background toward a new optimum
      and find the conditions for a complete sweep. Overall, our results suggest that
      phenotypic traits exhibiting clear-cut molecular signatures of selection may
      represent a biased subset of all adaptive traits.

PMID- 18832354
TI  - Identification of novel regulators of atonal expression in the developing
      Drosophila retina.
AB  - Atonal is a Drosophila proneural protein required for the proper formation of the
      R8 photoreceptor cell, the founding photoreceptor cell in the developing retina.
      Proper expression and refinement of the Atonal protein is essential for the
      proper formation of the Drosophila adult eye. In vertebrates, expression of
      transcription factors orthologous to Drosophila Atonal (MATH5/Atoh7, XATH5, and
      ATH5) and their progressive restriction are also involved in specifying the
      retinal ganglion cell, the founding neural cell type in the mammalian retina.
      Thus, identifying factors that are involved in regulating the expression of
      Atonal during development are important to fully understand how retinal
      neurogenesis is accomplished. We have performed a chemical mutagenesis screen for
      autosomal dominant enhancers of a loss-of-function atonal eye phenotype. We
      report here the identification of five genes required for proper Atonal
      expression, three of which are novel regulators of Atonal expression in the
      Drosophila retina. We characterize the role of the daughterless, kismet, and
      roughened eye genes on atonal transcriptional regulation in the developing retina
      and show that each gene regulates atonal transcription differently within the
      context of retinal development. Our results provide additional insights into the
      regulation of Atonal expression in the developing Drosophila retina.

PMID- 18832355
TI  - Unstable RNAi effects through epigenetic silencing of an inverted repeat
      transgene in Chlamydomonas reinhardtii.
AB  - RNA interferences in the unicellular green alga, Chlamydomonas reinhardtii, can
      be silenced. We have used the silencing of a transgene (aadA) that confers
      resistance to spectinomycin to investigate the mechanisms responsible for
      silencing by an artificial inverted repeat (IR) of the aadA gene. The IR
      construct provided strong silencing, but the RNAi efficiency varied among
      subclones of a single RNAi-transformed strain with successive cell divisions.
      Northern blot analyses revealed an inverse correlation between the copy number of
      the hairpin RNA and the spectinomycin resistance of the subclones. There is an
      inverse correlation between the efficiency of RNAi and the frequency of
      methylated CpG (*CpG) in the silenced region. No significant methylated cytosine
      was observed in the target aadA gene, which suggests the absence of RNA-directed
      DNA methylation in trans. Several experiments suggest the existence of an
      intrinsic IR sequence-dependent but a transcription-independent DNA methylation
      system in C. reinhardtii. The correlation between the *CpG levels and the IR
      transcript implies the existence of IR DNA-dependent DNA methylation. Treatment
      of RNAi-induced cells with a histone deacetylase inhibitor, Trichostatin A,
      rapidly increased the amount of the hairpin RNA and suggests that transcription
      of the silencer construct was repressed by *CpG-related silencing mechanisms.

PMID- 18832356
TI  - A simple formula for obtaining markedly improved mutation rate estimates.
AB  - In previous work by M. E. Jones and colleagues, it was shown that mutation rate
      estimates can be improved and corresponding confidence intervals tightened by
      following a very easy modification of the standard fluctuation assay: cultures
      are grown to a larger-than-usual final density, and mutants are screened for in
      only a fraction of the culture. Surprisingly, this very promising development has
      received limited attention, perhaps because there has been no efficient way to
      generate the predicted mutant distribution to obtain non-moment-based estimates
      of the mutation rate. Here, the improved fluctuation assay discovered by Jones
      and colleagues is made amenable to quantile-based, likelihood, and other Bayesian
      methods by a simple recursion formula that efficiently generates the entire
      mutant distribution after growth and dilution. This formula makes possible a
      further protocol improvement: grow cultures as large as is experimentally
      possible and severely dilute before plating to obtain easily countable numbers of
      mutants. A preliminary look at likelihood surfaces suggests that this easy
      protocol adjustment gives markedly improved mutation rate estimates and
      confidence intervals.

PMID- 18832357
TI  - Selection for environmental variation: a statistical analysis and power
      calculations to detect response.
AB  - Data from uterine capacity in rabbits (litter size) were analyzed to determine
      whether the environmental variance was partly genetically determined. The fit of
      a classical homogeneous variance mixed linear (HOM) model and that of a
      genetically structured heterogeneous variance mixed linear (HET) model were
      compared. Various methods to assess the quality of fit favor the HET model. The
      posterior mean (95% posterior interval) of the additive genetic variance
      affecting the environmental variance was 0.16 (0.10; 0.25) and the corresponding
      number for the coefficient of correlation between genes affecting mean and
      variance was -0.74 (-0.90;-0.52). It is argued that stronger support for the HET
      model than that derived from statistical analysis of data would be provided by a
      successful selection experiment designed to modify the environmental variance. A
      simple selection criterion is suggested (average squared deviation from the mean
      of repeated records within individuals) and its predicted response and variance
      under the HET model are derived. This is used to determine the appropriate size
      and length of a selection experiment designed to change the environmental
      variance. Results from the analytical expressions are compared with those
      obtained using simulation. There is good agreement provided selection intensity
      is not intense.

PMID- 18832358
TI  - Arabidopsis iba response5 suppressors separate responses to various hormones.
AB  - Auxin controls numerous plant growth processes by directing cell division and
      expansion. Auxin-response mutants, including iba response5 (ibr5), exhibit a long
      root and decreased lateral root production in response to exogenous auxins. ibr5
      also displays resistance to the phytohormone abscisic acid (ABA). We found that
      the sar3 suppressor of auxin resistant1 (axr1) mutant does not suppress ibr5
      auxin-response defects, suggesting that screening for ibr5 suppressors might
      reveal new components important for phytohormone responsiveness. We identified
      two classes of Arabidopsis thaliana mutants that suppressed ibr5 resistance to
      indole-3-butyric acid (IBA): those with restored responses to both the auxin
      precursor IBA and the active auxin indole-3-acetic acid (IAA) and those with
      restored response to IBA but not IAA. Restored IAA sensitivity was accompanied by
      restored ABA responsiveness, whereas suppressors that remained IAA resistant also
      remained ABA resistant. Some suppressors restored sensitivity to both natural and
      synthetic auxins; others restored responsiveness only to auxin precursors. We
      used positional information to determine that one ibr5 suppressor carried a
      mutation in PLEIOTROPIC DRUG RESISTANCE9 (PDR9/ABCG37/At3g53480), which encodes
      an ATP-binding cassette transporter previously implicated in cellular efflux of
      the synthetic auxin 2,4-dichlorophenoxyacetic acid.

PMID- 18832359
TI  - Clonal interference, multiple mutations and adaptation in large asexual
      populations.
AB  - Two important problems affect the ability of asexual populations to accumulate
      beneficial mutations and hence to adapt. First, clonal interference causes some
      beneficial mutations to be outcompeted by more-fit mutations that occur in the
      same genetic background. Second, multiple mutations occur in some individuals, so
      even mutations of large effect can be outcompeted unless they occur in a good
      genetic background that contains other beneficial mutations. In this article, we
      use a Monte Carlo simulation to study how these two factors influence the
      adaptation of asexual populations. We find that the results depend qualitatively
      on the shape of the distribution of the fitness effects of possible beneficial
      mutations. When this distribution falls off slower than exponentially, clonal
      interference alone reasonably describes which mutations dominate the adaptation,
      although it gives a misleading picture of the evolutionary dynamics. When the
      distribution falls off faster than exponentially, an analysis based on multiple
      mutations is more appropriate. Using our simulations, we are able to explore the
      limits of validity of both of these approaches, and we explore the complex
      dynamics in the regimes where neither one is fully applicable.

PMID- 18832360
TI  - Chromosome-scale genetic mapping using a set of 16 conditionally stable
      Saccharomyces cerevisiae chromosomes.
AB  - We have created a resource to rapidly map genetic traits to specific chromosomes
      in yeast. This mapping is done using a set of 16 yeast strains each containing a
      different chromosome with a conditionally functional centromere. Conditional
      centromere function is achieved by integration of a GAL1 promoter in cis to
      centromere sequences. We show that the 16 yeast chromosomes can be individually
      lost in diploid strains, which become hemizygous for the destabilized chromosome.
      Interestingly, most 2n - 1 strains endoduplicate and become 2n. We also
      demonstrate how chromosome loss in this set of strains can be used to map both
      recessive and dominant markers to specific chromosomes. In addition, we show that
      this method can be used to rapidly validate gene assignments from screens of
      strain libraries such as the yeast gene disruption collection.

PMID- 18832361
TI  - Overexpression screen in Drosophila identifies neuronal roles of GSK-3
      beta/shaggy as a regulator of AP-1-dependent developmental plasticity.
AB  - AP-1, an immediate-early transcription factor comprising heterodimers of the Fos
      and Jun proteins, has been shown in several animal models, including Drosophila,
      to control neuronal development and plasticity. In spite of this important role,
      very little is known about additional proteins that regulate, cooperate with, or
      are downstream targets of AP-1 in neurons. Here, we outline results from an
      overexpression/misexpression screen in Drosophila to identify potential
      regulators of AP-1 function at third instar larval neuromuscular junction (NMJ)
      synapses. First, we utilize >4000 enhancer and promoter (EP) and EPgy2 lines to
      screen a large subset of Drosophila genes for their ability to modify an AP-1
      dependent eye-growth phenotype. Of 303 initially identified genes, we use a set
      of selection criteria to arrive at 25 prioritized genes from the resulting
      collection of putative interactors. Of these, perturbations in 13 genes result in
      synaptic phenotypes. Finally, we show that one candidate, the GSK-3beta-kinase
      homolog, shaggy, negatively influences AP-1-dependent synaptic growth, by
      modulating the Jun-N-terminal kinase pathway, and also regulates presynaptic
      neurotransmitter release at the larval neuromuscular junction. Other candidates
      identified in this screen provide a useful starting point to investigate genes
      that interact with AP-1 in vivo to regulate neuronal development and plasticity.

PMID- 18832362
TI  - ARDB--Antibiotic Resistance Genes Database.
AB  - The treatment of infections is increasingly compromised by the ability of
      bacteria to develop resistance to antibiotics through mutations or through the
      acquisition of resistance genes. Antibiotic resistance genes also have the
      potential to be used for bio-terror purposes through genetically modified
      organisms. In order to facilitate the identification and characterization of
      these genes, we have created a manually curated database--the Antibiotic
      Resistance Genes Database (ARDB)--unifying most of the publicly available
      information on antibiotic resistance. Each gene and resistance type is annotated
      with rich information, including resistance profile, mechanism of action,
      ontology, COG and CDD annotations, as well as external links to sequence and
      protein databases. Our database also supports sequence similarity searches and
      implements an initial version of a tool for characterizing common mutations that
      confer antibiotic resistance. The information we provide can be used as
      compendium of antibiotic resistance factors as well as to identify the resistance
      genes of newly sequenced genes, genomes, or metagenomes. Currently, ARDB contains
      resistance information for 13,293 genes, 377 types, 257 antibiotics, 632 genomes,
      933 species and 124 genera. ARDB is available at http://ardb.cbcb.umd.edu/.

PMID- 18832363
TI  - PPDB, the Plant Proteomics Database at Cornell.
AB  - The Plant Proteomics Database (PPDB; http://ppdb.tc.cornell.edu), launched in
      2004, provides an integrated resource for experimentally identified proteins in
      Arabidopsis and maize (Zea mays). Internal BLAST alignments link maize and
      Arabidopsis information. Experimental identification is based on in-house mass
      spectrometry (MS) of cell type-specific proteomes (maize), or specific
      subcellular proteomes (e.g. chloroplasts, thylakoids, nucleoids) and total leaf
      proteome samples (maize and Arabidopsis). So far more than 5000 accessions both
      in maize and Arabidopsis have been identified. In addition, more than 80
      published Arabidopsis proteome datasets from subcellular compartments or organs
      are stored in PPDB and linked to each locus. Using MS-derived information and
      literature, more than 1500 Arabidopsis proteins have a manually assigned
      subcellular location, with a strong emphasis on plastid proteins. Additional new
      features of PPDB include searchable posttranslational modifications and
      searchable experimental proteotypic peptides and spectral count information for
      each identified accession based on in-house experiments. Various search methods
      are provided to extract more than 40 data types for each accession and to extract
      accessions for different functional categories or curated subcellular
      localizations. Protein report pages for each accession provide comprehensive
      overviews, including predicted protein properties, with hyperlinks to the most
      relevant databases.

PMID- 18832364
TI  - PID: the Pathway Interaction Database.
AB  - The Pathway Interaction Database (PID, http://pid.nci.nih.gov) is a freely
      available collection of curated and peer-reviewed pathways composed of human
      molecular signaling and regulatory events and key cellular processes. Created in
      a collaboration between the US National Cancer Institute and Nature Publishing
      Group, the database serves as a research tool for the cancer research community
      and others interested in cellular pathways, such as neuroscientists,
      developmental biologists and immunologists. PID offers a range of search features
      to facilitate pathway exploration. Users can browse the predefined set of
      pathways or create interaction network maps centered on a single molecule or
      cellular process of interest. In addition, the batch query tool allows users to
      upload long list(s) of molecules, such as those derived from microarray
      experiments, and either overlay these molecules onto predefined pathways or
      visualize the complete molecular connectivity map. Users can also download
      molecule lists, citation lists and complete database content in extensible markup
      language (XML) and Biological Pathways Exchange (BioPAX) Level 2 format. The
      database is updated with new pathway content every month and supplemented by
      specially commissioned articles on the practical uses of other relevant online
      tools.

PMID- 18832365
TI  - CleanEST: a database of cleansed EST libraries.
AB  - The EST division of GenBank, dbEST, is widely used in many applications such as
      gene discovery and verification of exon-intron structure. However, the use of EST
      sequences in the dbEST libraries is often hampered by inconsistent terminology
      used to describe the library sources and by the presence of contaminated
      sequences. Here, we describe CleanEST, a novel database server that classified
      dbEST libraries and removes contaminants. We classified all dbEST libraries
      according to species and sequencing center. In addition, we further classified
      human EST libraries by anatomical and pathological systems according to eVOC
      ontologies. For each dbEST library, we provide two different cleansed sequences:
      'pre-cleansed' and 'user-cleansed'. To generate pre-cleansed sequences, we
      cleansed sequences in dbEST by alignment of EST sequences against well-known
      contamination sources: UniVec, Escherichia coli, mitochondria and chloroplast
      (for plant). To provide user-cleansed sequences, we built an automatic user
      cleansing pipeline, in which sequences of a user-selected library are cleansed on
      the-fly according to user-selected options. The server is available at
      http://cleanest.kobic.re.kr/ and the database is updated monthly.

PMID- 18832366
TI  - Rapid and reliable universal cloning of influenza A virus genes by target-primed
      plasmid amplification.
AB  - Reverse genetics has become pivotal in influenza virus research relying on rapid
      generation of tailored recombinant influenza viruses. They are rescued from
      transfected plasmids encoding the eight influenza virus gene segments, which have
      been cloned using restriction endonucleases and DNA ligation. However, suitable
      restriction cleavage sites often are not available. Here, we describe a cloning
      method universal for any influenza A virus strain which is independent of
      restriction sites. It is based on target-primed plasmid amplification in which
      the insert provides two megaprimers and contains termini homologous to plasmid
      regions adjacent to the insertion site. For improved efficiency, a cloning vector
      was designed containing the negative selection marker ccdB flanked by the highly
      conserved influenza A virus gene termini. Using this method, we generated
      complete sets of functional gene segments from seven influenza A strains and
      three haemagglutinin genes from different serotypes amounting to 59 cloned
      influenza genes. These results demonstrate that this approach allows rapid and
      reliable cloning of any segment from any influenza A strain without any
      information about restriction sites. In case the PCR amplicon ends are homologous
      to the plasmid annealing sites only, this method is suitable for cloning of any
      insert with conserved termini.

PMID- 18832367
TI  - PhyloPat: an updated version of the phylogenetic pattern database contains gene
      neighborhood.
AB  - Phylogenetic patterns show the presence or absence of certain genes in a set of
      full genomes derived from different species. They can also be used to determine
      sets of genes that occur only in certain evolutionary branches. Previously, we
      presented a database named PhyloPat which allows the complete Ensembl gene
      database to be queried using phylogenetic patterns. Here, we describe an updated
      version of PhyloPat which can be queried by an improved web server. We used a
      single linkage clustering algorithm to create 241,697 phylogenetic lineages,
      using all the orthologies provided by Ensembl v49. PhyloPat offers the
      possibility of querying with binary phylogenetic patterns or regular expressions,
      or through a phylogenetic tree of the 39 included species. Users can also input a
      list of Ensembl, EMBL, EntrezGene or HGNC IDs to check which phylogenetic lineage
      any gene belongs to. A link to the FatiGO web interface has been incorporated in
      the HTML output. For each gene, the surrounding genes on the chromosome, color
      coded according to their phylogenetic lineage can be viewed, as well as FASTA
      files of the peptide sequences of each lineage. Furthermore, lists of
      omnipresent, polypresent, oligopresent and anticorrelating genes have been
      included. PhyloPat is freely available at http://www.cmbi.ru.nl/phylopat.

PMID- 18832368
TI  - GermSAGE: a comprehensive SAGE database for transcript discovery on male germ
      cell development.
AB  - GermSAGE is a comprehensive web-based database generated by Serial Analysis of
      Gene Expression (SAGE) representing major stages in mouse male germ cell
      development, with 150,000 sequence tags in each SAGE library. A total of 452,095
      tags derived from type A spermatogonia (Spga), pachytene spermatocytes (Spcy) and
      round spermatids (Sptd) were included. GermSAGE provides web-based tools for
      browsing, comparing and searching male germ cell transcriptome data at different
      stages with customizable searching parameters. The data can be visualized in a
      tabulated format or further analyzed by aligning with various annotations
      available in the UCSC genome browser. This flexible platform will be useful for
      gaining better understanding of the genetic networks that regulate spermatogonial
      cell renewal and differentiation, and will allow novel gene discovery. GermSAGE
      is freely available at http://germsage.nichd.nih.gov/

PMID- 18832369
TI  - JAIL: a structure-based interface library for macromolecules.
AB  - The increasing number of solved macromolecules provides a solid number of 3D
      interfaces, if all types of molecular contacts are being considered. JAIL
      annotates three different kinds of macromolecular interfaces, those between
      interacting protein domains, interfaces of different protein chains and
      interfaces between proteins and nucleic acids. This results in a total number of
      about 184,000 database entries. All the interfaces can easily be identified by a
      detailed search form or by a hierarchical tree that describes the protein domain
      architectures classified by the SCOP database. Visual inspection of the
      interfaces is possible via an interactive protein viewer. Furthermore, large
      scale analyses are supported by an implemented sequential and by a structural
      clustering. Similar interfaces as well as non-redundant interfaces can be easily
      picked out. Additionally, the sequential conservation of binding sites was also
      included in the database and is retrievable via Jmol. A comprehensive download
      section allows the composition of representative data sets with user defined
      parameters. The huge data set in combination with various search options allow a
      comprehensive view on all interfaces between macromolecules included in the
      Protein Data Bank (PDB). The download of the data sets supports numerous further
      investigations in macromolecular recognition. JAIL is publicly available at
      http://bioinformatics.charite.de/jail.

PMID- 18832370
TI  - G-quadruplexes: the beginning and end of UTRs.
AB  - Molecular mechanisms that regulate gene expression can occur either before or
      after transcription. The information for post-transcriptional regulation can lie
      within the sequence or structure of the RNA transcript and it has been proposed
      that G-quadruplex nucleic acid sequence motifs may regulate translation as well
      as transcription. Here, we have explored the incidence of G-quadruplex motifs in
      and around the untranslated regions (UTRs) of mRNA. We observed a significant
      strand asymmetry, consistent with a general depletion of G-quadruplex-forming
      RNA. We also observed a positional bias in two distinct regions, each suggestive
      of a specific function. We observed an excess of G-quadruplex motifs towards the
      5'-ends of 5'-UTRs, supportive of a hypothesis linking 5'-UTR RNA G-quadruplexes
      to translational control. We then analysed the vicinity of 3'-UTRs and observed
      an over-representation of G-quadruplex motifs immediately after the 3'-end of
      genes, especially in those cases where another gene is in close proximity,
      suggesting that G-quadruplexes may be involved in the termination of gene
      transcription.

PMID- 18832371
TI  - Ribosomal protein L3 functions as a 'rocker switch' to aid in coordinating of
      large subunit-associated functions in eukaryotes and Archaea.
AB  - Although ribosomal RNAs (rRNAs) comprise the bulk of the ribosome and carry out
      its main functions, ribosomal proteins also appear to play important structural
      and functional roles. Many ribosomal proteins contain long, nonglobular domains
      that extend deep into the rRNA cores. In eukaryotes and Archaea, ribosomal
      protein L3 contains two such extended domains tethered to a common globular hub,
      thus providing an excellent model to address basic questions relating to
      ribosomal protein structure/function relationships. Previous work in our
      laboratory identified the central 'W-finger' extension of yeast L3 in helping to
      coordinate ribosomal functions. New studies on the 'N-terminal' extension in
      yeast suggest that it works with the W-finger to coordinate opening and closing
      of the corridor through which the 3' end of aa-tRNA moves during the process of
      accommodation. Additionally, the effect of one of the L3 N-terminal extension
      mutants on the interaction between C75 of the aa-tRNA and G2921 (Escherichia coli
      G2553) of 25S rRNA provides the first evidence of the effect of a ribosomal
      protein on aa-tRNA positioning and peptidyltransfer, possibly through the induced
      fit model. A model is presented describing how all three domains of L3 may
      function together as a 'rocker switch' to coordinate the stepwise processes of
      translation elongation.

PMID- 18832372
TI  - Modeling genetic inheritance of copy number variations.
AB  - Copy number variations (CNVs) are being used as genetic markers or functional
      candidates in gene-mapping studies. However, unlike single nucleotide
      polymorphism or microsatellite genotyping techniques, most CNV detection methods
      are limited to detecting total copy numbers, rather than copy number in each of
      the two homologous chromosomes. To address this issue, we developed a statistical
      framework for intensity-based CNV detection platforms using family data. Our
      algorithm identifies CNVs for a family simultaneously, thus avoiding the
      generation of calls with Mendelian inconsistency while maintaining the ability to
      detect de novo CNVs. Applications to simulated data and real data indicate that
      our method significantly improves both call rates and accuracy of boundary
      inference, compared to existing approaches. We further illustrate the use of
      Mendelian inheritance to infer SNP allele compositions in each of the two
      homologous chromosomes in CNV regions using real data. Finally, we applied our
      method to a set of families genotyped using both the Illumina HumanHap550 and
      Affymetrix genome-wide 5.0 arrays to demonstrate its performance on both
      inherited and de novo CNVs. In conclusion, our method produces accurate CNV
      calls, gives probabilistic estimates of CNV transmission and builds a solid
      foundation for the development of linkage and association tests utilizing CNVs.

PMID- 18832373
TI  - Evolutionary origins of human apoptosis and genome-stability gene networks.
AB  - Apoptosis is essential for complex multicellular organisms and its failure is
      associated with genome instability and cancer. Interactions between apoptosis and
      genome-maintenance mechanisms have been extensively documented and include
      transactivation-independent and -dependent functions, in which the tumor
      suppressor protein p53 works as a 'molecular node' in the DNA-damage response.
      Although apoptosis and genome stability have been identified as ancient pathways
      in eukaryote phylogeny, the biological evolution underlying the emergence of an
      integrated system remains largely unknown. Here, using computational methods, we
      reconstruct the evolutionary scenario that linked apoptosis with genome stability
      pathways in a functional human gene/protein association network. We found that
      the entanglement of DNA repair, chromosome stability and apoptosis gene networks
      appears with the caspase gene family and the antiapoptotic gene BCL2. Also,
      several critical nodes that entangle apoptosis and genome stability are cancer
      genes (e.g. ATM, BRCA1, BRCA2, MLH1, MSH2, MSH6 and TP53), although their
      orthologs have arisen in different points of evolution. Our results demonstrate
      how genome stability and apoptosis were co-opted during evolution recruiting
      genes that merge both systems. We also provide several examples to exploit this
      evolutionary platform, where we have judiciously extended information on gene
      essentiality inferred from model organisms to human.

PMID- 18832374
TI  - Overexpression of the LexA-regulated tisAB RNA in E. coli inhibits SOS functions;
      implications for regulation of the SOS response.
AB  - The DNA damage induced SOS response in Escherichia coli is initiated by cleavage
      of the LexA repressor through activation of RecA. Here we demonstrate that
      overexpression of the SOS-inducible tisAB gene inhibits several SOS functions in
      vivo. Wild-type E. coli overexpressing tisAB showed the same UV sensitivity as a
      lexA mutant carrying a noncleavable version of the LexA protein unable to induce
      the SOS response. Immunoblotting confirmed that tisAB overexpression leads to
      higher levels of LexA repressor and northern experiments demonstrated delayed and
      reduced induction of recA mRNA. In addition, induction of prophage lambda and UV
      induced filamentation was inhibited by tisAB overexpression. The tisAB gene
      contains antisense sequences to the SOS-inducible dinD gene (16 nt) and the uxaA
      gene (20 nt), the latter encoding a dehydratase essential for galacturonate
      catabolism. Cleavage of uxaA mRNA at the antisense sequence was dependent on
      tisAB RNA expression. We showed that overexpression of tisAB is less able to
      confer UV sensitivity to the uxaA dinD double mutant as compared to wild-type,
      indicating that the dinD and uxaA transcripts modulate the anti-SOS response of
      tisAB. These data shed new light on the complexity of SOS regulation in which the
      uxaA gene could link sugar metabolism to the SOS response via antisense
      regulation of the tisAB gene.

PMID- 18832375
TI  - Analysis of factor interactions with RNA polymerase II elongation complexes using
      a new electrophoretic mobility shift assay.
AB  - The elongation phase of transcription by RNA polymerase II (RNAP II) is
      controlled by a carefully orchestrated series of interactions with both negative
      and positive factors. However, due to the limitations of current methods and
      techniques, not much is known about whether and how these proteins physically
      associate with the engaged polymerases. To gain insight into the detailed
      mechanisms involved, we established an experimental system for analyzing direct
      factor interactions to RNAP II elongation complexes on native gels, namely
      elongation complex electrophoretic mobility shift assay (EC-EMSA). This new assay
      effectively allowed detection of interactions of TFIIF, TTF2, TFIIS, DSIF and P
      TEFb with elongation complexes generated from a natural promoter using an
      immobilized template. As an application of this assay system, we characterized
      the association of transcription elongation factor DSIF with RNAP II elongation
      complexes and discovered that the nascent transcript facilitated recruitment of
      DSIF. Examples of how the system can be manipulated to address different
      questions are provided. EC-EMSA should be useful for further investigation of
      factor interactions with RNAP II elongation complexes.

PMID- 18832376
TI  - Context dependent function of APPb enhancer identified using enhancer trap
      containing BACs as transgenes in zebrafish.
AB  - An enhancer within intron 1 of the amyloid precursor protein gene (APPb) of
      zebrafish is identified functionally using a novel approach. Bacterial artificial
      chromosomes (BACs) were retrofitted with enhancer traps, and expressed as
      transgenes in zebrafish. Expression from both transient assays and stable lines
      were used for analysis. Although the enhancer was active in specific nonneural
      cells of the notochord when placed with APPb gene promoter proximal elements its
      function was restricted to, and absolutely required for, specific expression in
      neurons when juxtaposed with additional far-upstream promoter elements of the
      gene. We demonstrate that expression of green fluorescent protein fluorescence
      resembling the tissue distribution of APPb mRNA requires both the intron 1
      enhancer and approximately 28 kb of DNA upstream of the gene. The results
      indicate that tissue-specificity of an isolated enhancer may be quite different
      from that in the context of its own gene. Using this enhancer and upstream
      sequence, polymorphic variants of APPb can now more closely recapitulate the
      endogenous pattern and regulation of APPb expression in animal models for
      Alzheimer's disease. The methodology should help functionally map multiple
      noncontiguous regulatory elements in BACs with or without gene-coding sequences.

PMID- 18832377
TI  - Riboflavin is an active redox cofactor in the Na+-pumping NADH: quinone
      oxidoreductase (Na+-NQR) from Vibrio cholerae.
AB  - Here we present new evidence that riboflavin is present as one of four flavins in
      Na+-NQR. In particular, we present conclusive evidence that the source of the
      neutral radical is not one of the FMNs and that riboflavin is the center that
      gives rise to the neutral flavosemiquinone. The riboflavin is a bona fide redox
      cofactor and is likely to be the last redox carrier of the enzyme, from which
      electrons are donated to quinone. We have constructed a double mutant that lacks
      both covalently bound FMN cofactors (NqrB-T236Y/NqrC-T225Y) and have studied this
      mutant together with the two single mutants (NqrB-T236Y and NqrC-T225Y) and a
      mutant that lacks the noncovalently bound FAD in NqrF (NqrF-S246A). The double
      mutant contains riboflavin and FAD in a 0.6:1 ratio, as the only flavins in the
      enzyme; noncovalently bound flavins were detected. In the oxidized form, the
      double mutant exhibits an EPR signal consistent with a neutral flavosemiquinone
      radical, which is abolished on reduction of the enzyme. The same radical can be
      observed in the FAD deletion mutant. Furthermore, when the oxidized enzyme reacts
      with ubiquinol (the reduced form of the usual electron acceptor) in a process
      that reverses the physiological direction of the electron flow, a single kinetic
      phase is observed. The kinetic difference spectrum of this process is consistent
      with one-electron reduction of a neutral flavosemiquinone. The presence of
      riboflavin in the role of a redox cofactor is thus far unique to Na+-NQR.

PMID- 18832378
TI  - Selective actions of mitochondrial fission/fusion genes on metabolism-secretion
      coupling in insulin-releasing cells.
AB  - Mitochondria form filamentous networks that undergo continuous fission/fusion. In
      the pancreatic beta-cells, mitochondria are essential for the transduction of
      signals linking nutrient metabolism to insulin granule exocytosis. Here we have
      studied mitochondrial networks in the insulinoma cell line INS-1E, primary rat
      and human beta-cells. We have further investigated the impact of mitochondrial
      fission/fusion on metabolism-secretion coupling in INS-1E cells. Overexpression
      of hFis1 caused dramatic mitochondrial fragmentation, whereas Mfn1 evoked
      hyperfusion and the aggregation of mitochondria. Cells overexpressing hFis1 or
      Mfn1 showed reduced mitochondrial volume, lowered cellular ATP levels, and as a
      consequence, impaired glucose-stimulated insulin secretion. Decreased
      mitochondrial ATP generation was partially compensated for by enhanced glycolysis
      as indicated by increased lactate production in these cells. Dominant-negative
      Mfn1 elicited mitochondrial shortening and fragmentation of INS-1E cell
      mitochondria, similar to hFis1. However, the mitochondrial volume, cytosolic ATP
      levels, and glucose-stimulated insulin secretion were little affected. We
      conclude that mitochondrial fragmentation per se does not impair metabolism
      secretion coupling. Through their impact on mitochondrial bioenergetics and
      distribution, hFis1 and Mfn1 activities influence mitochondrial signal generation
      thereby insulin exocytosis.

PMID- 18832379
TI  - Ricin B chain targeted to the endoplasmic reticulum of tobacco protoplasts is
      degraded by a CDC48- and vacuole-independent mechanism.
AB  - The B chain of ricin was expressed and delivered to the endoplasmic reticulum of
      tobacco protoplasts where it disappeared with time in a manner consistent with
      degradation. This turnover did not occur in the vacuoles or upon secretion.
      Indeed, several lines of evidence indicate that, in contrast to the turnover of
      endoplasmic reticulum-targeted ricin A chain in the cytosol, the bulk of
      expressed ricin B chain was degraded in the secretory pathway.

PMID- 18832380
TI  - Antisense masking reveals contributions of mRNA-rRNA base pairing to translation
      of Gtx and FGF2 mRNAs.
AB  - We previously showed that a 9-nucleotide sequence from the 5' leader of the Gtx
      homeodomain mRNA facilitates translation initiation by base pairing to 18S rRNA.
      These earlier studies tested the Gtx element in isolation; we now assess the
      physiological relevance of this element in the context of two natural mRNAs that
      contain this sequence in their 5' leaders, Gtx itself and FGF2 (fibroblast growth
      factor 2). 2'-O-Methyl-modified RNA oligonucleotides were employed to block mRNA
      rRNA base pairing by targeting either the Gtx-binding site in 18S rRNA or Gtx
      elements in recombinant mRNAs containing the Gtx or FGF2 5' leaders linked to a
      reporter cistron. Studies in cell-free lysates and transfected COS-7 cells showed
      that translation of mRNAs containing the Gtx or FGF2 5' leaders was decreased by
      > 50% when oligonucleotides targeting either the rRNA or mRNA were used.
      Specificity was demonstrated by showing that translation of the recombinant mRNAs
      was unaffected by control oligonucleotides. In addition, the specific
      oligonucleotides did not affect the translation of recombinant mRNAs in which the
      Gtx elements were mutated. Experiments performed using constructs containing Gtx
      and FGF2 5' leader and coding sequences ruled out possible effects of the
      reporter cistron. Furthermore, two-dimensional gel electrophoresis revealed that
      the oligonucleotides used in this study had little overall effect on the
      proteomes of cells transfected with these oligonucleotides. This study
      demonstrates that mRNA-rRNA base pairing affects the expression of two cellular
      mRNAs and describes a new approach for investigating putative mRNA-rRNA base
      pairing interactions in mammalian cells.

PMID- 18832381
TI  - A C-terminal sequence in the guanine nucleotide exchange factor Sec7 mediates
      Golgi association and interaction with the Rsp5 ubiquitin ligase.
AB  - Arf GTPases control vesicle formation from different intracellular membranes and
      are regulated by Arf guanine nucleotide exchange factors (GEFs). Outside of their
      conserved catalytic domains, known as Sec7 domains, little is known about Arf
      GEFs. Rsp5 is a yeast ubiquitin ligase that regulates numerous membrane
      trafficking events and carries a C2 domain that is specifically required for
      trans-Golgi network to vacuole transport. In a screen for proteins that interact
      with the Rsp5 C2 domain we identified Sec7, the GEF that acts on Golgi-associated
      Arfs. The Rsp5-Sec7 interaction is direct, occurs in vivo, and is conserved among
      mammalian Rsp5 and Sec7 homologues. A 50-amino acid region near the Sec7 C
      terminus is required for Rsp5 binding and for normal Sec7 localization. Binding
      of Sec7 to Rsp5 is dependent on the presence of the phosphoinositide 3-kinase
      Vps34, suggesting that phosphatidylinositol 3-phosphate (PI(3)P) plays a role in
      regulating this interaction. Overexpression of Sec7 significantly suppresses the
      growth and sorting defects of an rsp5 C2 domain point mutant. These observations
      identify a new functional region within the Sec7/BIG family of Arf GEFs that is
      required for trans-Golgi network localization.

PMID- 18832382
TI  - HMGA2 and Smads co-regulate SNAIL1 expression during induction of epithelial-to
      mesenchymal transition.
AB  - Epithelial-mesenchymal transition (EMT) is important during embryonic cell layer
      movement and tumor cell invasiveness. EMT converts adherent epithelial cells to
      motile mesenchymal cells, favoring metastasis in the context of cancer
      progression. Transforming growth factor-beta (TGF-beta) triggers EMT via
      intracellular Smad transducers and other signaling proteins. We previously
      reported that the high mobility group A2 (HMGA2) gene is required for TGF-beta to
      elicit EMT in mammary epithelial cells. In the present study we investigated the
      molecular mechanisms by which HMGA2 induces EMT. We found that HMGA2 regulates
      expression of many important repressors of E-cadherin. Among these, we analyzed
      in detail the zinc-finger transcription factor SNAIL1, which plays key roles in
      tumor progression and EMT. We demonstrate that HMGA2 directly binds to the SNAIL1
      promoter and acts as a transcriptional regulator of SNAIL1 expression.
      Furthermore, we observed that HMGA2 cooperates with the TGF-beta/Smad pathway in
      regulating SNAIL1 gene expression. The mechanism behind this cooperation involves
      physical interaction between these factors, leading to an increased binding of
      Smads to the SNAIL1 promoter. SNAIL1 seems to play the role of a master effector
      downstream of HMGA2 for induction of EMT, as SNAIL1 knock-down partially reverts
      HMGA2-induced loss of epithelial differentiation. The data propose that HMGA2
      acts in a gene-specific manner to orchestrate the transcriptional network
      necessary for the EMT program.

PMID- 18832383
TI  - Aortic valve stenosis management: old strategies and future directions.

PMID- 18832384
TI  - Changes of the corrected QT interval in healthy boys and girls over day and
      night.
AB  - AIMS: The study was designed to detect changes in corrected QT intervals over day
      and night in both sexes in healthy children. METHODS AND RESULTS: The corrected
      QT interval was calculated from 24 h ECGs obtained from 282 healthy children aged
      6 months to 18 years. The QTc interval as measured by the 24 h recording differs
      to the standard ECG measurement which is in average of 40-50 ms shorter. The QTc
      interval changes little over a 24 h period and is remarkably constant despite
      significant heart rate changes in healthy children. CONCLUSION: The routine ECG
      even if the calculated values differ markedly from those obtained over 24 h-seems
      to be a good screening method for the measurement of corrected QT intervals,
      because the corrected QT interval is kept constant over the whole day in healthy
      children.

PMID- 18832385
TI  - Neointimal hyperplasia after sirolimus-eluting and paclitaxel-eluting stent
      implantation in diabetic patients: the Randomized Diabetes and Drug-Eluting Stent
      (DiabeDES) Intravascular Ultrasound Trial.
AB  - AIMS: Patients with diabetes have increased risk of in-stent restenosis after
      coronary stent implantation owing to neointimal hyperplasia (NIH). The aim of the
      study was to evaluate the extent and distribution of NIH with intravascular
      ultrasound (IVUS) after coronary artery stenting with sirolimus-eluting (Cypher)
      or paclitaxel-eluting (Taxus) stents in diabetic patients. METHODS AND RESULTS:
      One hundred and thirty diabetic patients were randomized to Cypher or Taxus stent
      implantation. IVUS was performed at 8 month follow-up. NIH volume was
      significantly reduced in the Cypher group when compared with the Taxus group:
      median (inter-quartile range) 0.0 (0.0-0.0) vs. 8.0 mm(3) (0.1-33.0), P < 0.001.
      Per cent NIH volume was also significantly lower in Cypher stents compared with
      Taxus stents: median (inter-quartile range) 0.0 (0.0-0.0) vs. 7.5% (0.1-27.0), P
      < 0.001. NIH was covering 5.4% of the stent length in the Cypher stents compared
      with 46.1% in the Taxus stents (P < 0.001). The incidence of diffuse NIH was
      significantly higher for Taxus than for Cypher stents (42.9 vs. 3.5%, P < 0.001).
      Taxus stents had more often NIH at the proximal stent edge compared with Cypher
      stents (45.1 vs. 7%, P < 0.001) and no Cypher stents had NIH at the distal stent
      edge compared with 35.5% of the Taxus stents (P < 0.001). CONCLUSION: In diabetic
      patients, the Cypher stent, compared with the Taxus stent, inhibited NIH more
      effectively and had a more focal NIH pattern including less involvement of the
      stent edges.

PMID- 18832386
TI  - Commentary: Flawed study designs are not salvaged by large samples.

PMID- 18832387
TI  - Consumption of green and roasted teas and the risk of stroke incidence: results
      from the Tokamachi-Nakasato cohort study in Japan.
AB  - BACKGROUND: and purpose Green tea consumption is inversely associated with death
      from stroke. The purpose of the present study was to assess whether it is
      inversely associated with subsequent stroke incidence and whether this
      association is preserved even with roasted tea leaves. METHODS: In 1998, 6358
      Japanese adults (2087 men and 4271 women) aged 40-89 years without a history of
      stroke or heart disease completed a lifestyle questionnaire, including
      consumption of green tea or roasted tea. By the end of 2003, 110 stroke events
      (59 cerebral infarction events, 34 cerebral haemorrhage events, 15 subarachnoidal
      haemorrhage events and two stroke events of unspecified subtype) had been
      documented. Cox proportional hazards regression analysis was used to calculate
      the multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (95%
      CIs) for total stroke events, cerebral infarction events and cerebral haemorrhage
      events according to consumption categories of green tea and roasted tea. RESULTS:
      A considerably lower risk was observed for total stroke incidence in both the
      middle (multivariable HR, 0.43; 95% CI, 0.25-0.74; P = 0.002) and the high
      (multivariable HR, 0.41; 95% CI, 0.24-0.70; P = 0.001) categories of green tea
      consumption. This inverse association was consistent even when cerebral
      infarction and cerebral haemorrhage were analysed separately. The consumption of
      roasted tea was not associated with stroke risk. CONCLUSIONS: Green tea
      consumption is associated with a reduced risk of total stroke incidence, cerebral
      infarction and cerebral haemorrhage.

PMID- 18832388
TI  - Commentary: Heterogeneity in meta-analysis should be expected and appropriately
      quantified.

PMID- 18832389
TI  - PTEN deficiency causes dyschondroplasia in mice by enhanced hypoxia-inducible
      factor 1alpha signaling and endoplasmic reticulum stress.
AB  - Chondrocytes within the growth plates acclimatize themselves to a variety of
      stresses that might otherwise disturb cell fate. The tumor suppressor PTEN
      (phosphatase and tensin homolog deleted from chromosome 10) has been implicated
      in the maintenance of cell homeostasis. However, the functions of PTEN in
      regulating chondrocytic adaptation to stresses remain largely unknown. In this
      study, we have created chondrocyte-specific Pten knockout mice
      (Pten(co/co);Col2a1-Cre) using the Cre-loxP system. Following AKT activation,
      Pten mutant mice exhibited dyschondroplasia resembling human enchondroma.
      Cartilaginous nodules originated from Pten mutant resting chondrocytes that
      suffered from impaired proliferation and differentiation, and this was coupled
      with enhanced endoplasmic reticulum (ER) stress. We further found that ER stress
      in Pten mutant chondrocytes only occurred under hypoxic stress, characterized by
      an upregulation of unfolded protein response-related genes as well as an engorged
      and fragmented ER in which collagens were trapped. An upregulation of hypoxia
      inducible factor 1alpha (HIF1alpha) and downstream targets followed by ER stress
      induction was also observed in Pten mutant growth plates and in cultured
      chondrocytes, suggesting that PI3K/AKT signaling modulates chondrocytic
      adaptation to hypoxic stress via regulation of the HIF1alpha pathway. These data
      demonstrate that PTEN function in chondrocytes is essential for their adaptation
      to stresses and for the inhibition of dyschondroplasia.

PMID- 18832390
TI  - An essential role for frizzled 5 in mammalian ocular development.
AB  - Microphthalmia, coloboma and persistent fetal vasculature within the vitreous
      cavity are among the most common human congenital ocular anomalies, and each has
      been associated with a variety of genetic disorders. Here we show that, in the
      mouse, loss of frizzled 5 (Fz5) - a putative Wnt receptor expressed in the eye
      field, optic cup and retina - causes all of these defects with high penetrance.
      In the developing Fz5(-/-) eye, the sequence of defects, in order of appearance,
      is: increased cell death in the ventral retina, delayed and/or incomplete closure
      of the ventral fissure, an excess of mesenchymal cells in the vitreous cavity, an
      excess of retinal astrocyte precursors and mature astrocytes, and persistence of
      the hyaloid vasculature in association with a large number of pigment cells. Fz5(
      /-) mice also exhibit a late-onset progressive retinal degeneration by
      approximately 6 months of age, which might be related to the expression of Fz5 in
      Muller glia in the adult retina. These results demonstrate a central role for
      frizzled signaling in mammalian eye development and are likely to be relevant to
      the etiology of congenital human ocular anomalies.

PMID- 18832391
TI  - Functional resolution of duplicated hoxb5 genes in teleosts.
AB  - The duplication-degeneration-complementation (DDC) model predicts that
      subfunctionalization of duplicated genes is a common mechanism for their
      preservation. The additional Hox complexes of teleost fish constitute a good
      system in which to test this hypothesis. Zebrafish have two hoxb complexes, with
      two hoxb5 genes, hoxb5a and hoxb5b, the expression patterns of which suggest
      subfunctionalization of an ancestral hoxb5 gene. We characterized conserved non
      coding elements (CNEs) near the zebrafish hoxb5 genes. One CNE, J3, is only
      retained in the hoxb5a locus, whereas the others, J1 and J2, are present in both
      hoxb5 loci. When tested individually, the enhancer activity of individual CNEs,
      including J3, extensively overlapped and did not support a role in
      subfunctionalization. By contrast, reporter transgene constructs encompassing
      multiple CNEs were able to target reporter gene expression to unique domains of
      hoxb5a and hoxb5b expression. The deletion of J3 from the hoxb5a locus resulted
      in expression that approached that of hoxb5b, whereas its insertion in the hoxb5b
      locus increased reporter expression and rendered it more similar to that of
      hoxb5a. Our results highlight the importance of interactions between CNEs in the
      execution of complementary subfunctions of duplicated genes.

PMID- 18832392
TI  - An FGF autocrine loop initiated in second heart field mesoderm regulates
      morphogenesis at the arterial pole of the heart.
AB  - In order to understand how secreted signals regulate complex morphogenetic
      events, it is crucial to identify their cellular targets. By conditional
      inactivation of Fgfr1 and Fgfr2 and overexpression of the FGF antagonist sprouty
      2 in different cell types, we have dissected the role of FGF signaling during
      heart outflow tract development in mouse. Contrary to expectation, cardiac neural
      crest and endothelial cells are not primary paracrine targets. FGF signaling
      within second heart field mesoderm is required for remodeling of the outflow
      tract: when disrupted, outflow myocardium fails to produce extracellular matrix
      and TGFbeta and BMP signals essential for endothelial cell transformation and
      invasion of cardiac neural crest. We conclude that an autocrine regulatory loop,
      initiated by the reception of FGF signals by the mesoderm, regulates correct
      morphogenesis at the arterial pole of the heart. These findings provide new
      insight into how FGF signaling regulates context-dependent cellular responses
      during development.

PMID- 18832393
TI  - Frs2alpha-deficiency in cardiac progenitors disrupts a subset of FGF signals
      required for outflow tract morphogenesis.
AB  - The cardiac outflow tract (OFT) is a developmentally complex structure derived
      from multiple lineages and is often defective in human congenital anomalies.
      Although emerging evidence shows that fibroblast growth factor (FGF) is essential
      for OFT development, the downstream pathways mediating FGF signaling in cardiac
      progenitors remain poorly understood. Here, we report that FRS2alpha (FRS2), an
      adaptor protein that links FGF receptor kinases to multiple signaling pathways,
      mediates crucial aspects of FGF-dependent OFT development in mouse. Ablation of
      Frs2alpha in mesodermal OFT progenitor cells that originate in the second heart
      field (SHF) affects their expansion into the OFT myocardium, resulting in OFT
      misalignment and hypoplasia. Moreover, Frs2alpha mutants have defective
      endothelial-to-mesenchymal transition and neural crest cell recruitment into the
      OFT cushions, resulting in OFT septation defects. These results provide new
      insight into the signaling molecules downstream of FGF receptor tyrosine kinases
      in cardiac progenitors.

PMID- 18832394
TI  - Pdm and Castor close successive temporal identity windows in the NB3-1 lineage.
AB  - Neurogenesis in Drosophila and mammals requires the precise integration of
      spatial and temporal cues. In Drosophila, embryonic neural progenitors
      (neuroblasts) sequentially express the transcription factors Hunchback, Kruppel,
      Pdm1/Pdm2 (Pdm) and Castor as they generate a stereotyped sequence of neuronal
      and glial progeny. Hunchback and Kruppel specify early temporal identity in two
      posterior neuroblast lineages (NB7-1 and NB7-3), whereas Pdm and Castor specify
      late neuronal identity in the NB7-1 lineage. Because Pdm and Castor have only
      been assayed in one lineage, it is unknown whether their function is restricted
      to neuronal identity in the NB7-1 lineage, or whether they function more broadly
      as late temporal identity genes in all neuroblast lineages. Here, we identify
      neuronal birth-order and molecular markers within the NB3-1 cell lineage, and
      then use this lineage to assay Pdm and Castor function. We show that Hunchback
      and Kruppel specify first and second temporal identities, respectively.
      Surprisingly, Pdm does not specify the third temporal identity, but instead acts
      as a timing factor to close the second temporal identity window. Similarly,
      Castor closes the third temporal identity window. We conclude that Hunchback and
      Kruppel specify the first and second temporal identities, an unknown factor
      specifies the third temporal identity, and Pdm and Castor are timing factors that
      close the second and third temporal identity windows in the NB3-1 lineage. Our
      results provide a new neuroblast lineage for investigating temporal identity and
      reveal the importance of Pdm and Cas as timing factors that close temporal
      identity windows.

PMID- 18832395
TI  - Autonomous and non-autonomous Shh signalling mediate the in vivo growth and
      guidance of mouse retinal ganglion cell axons.
AB  - In non-mammalian vertebrates, the relatively homogeneous population of retinal
      ganglion cells (RGCs) differentiates and projects entirely to the contralateral
      side of the brain under the influence of sonic hedgehog (Shh). In mammals, by
      contrast, there are two different RGC types: the Zic2-positive ipsilateral
      projecting and the Isl2-positive contralateral projecting. We asked whether the
      axons of these two populations respond to Shh and if their response differs. We
      have also analysed whether midline- and RGC-derived Shh contributes to the growth
      of the axons in the proximal visual pathway. We show that these two RGC types are
      characterised by a differential expression of Shh signalling components and that
      they respond differently to Shh when challenged in vitro. In vivo blockade of Shh
      activity, however, alters the path and distribution mostly of the contralateral
      projecting RGC axons at the chiasm, indicating that midline-derived Shh
      participates in funnelling contralateral visual fibres in this region.
      Furthermore, interference with Shh signalling in the RGCs themselves causes
      abnormal growth and navigation of contralateral projecting axons in the proximal
      portion of the pathway, highlighting a novel cell-autonomous mechanism by which
      Shh can influence growth cone behaviour.

PMID- 18832396
TI  - PDGF signalling controls the migration of mesoderm cells during chick
      gastrulation by regulating N-cadherin expression.
AB  - In the early chick embryo, Pdgfa is expressed in the epiblast, outlining the
      migration route that mesoderm cells expressing the receptor, Pdgfralpha, follow
      to form somites. Both expression of a dominant-negative PDGFRalpha and depletion
      of endogenous PDGFRalpha ligands through injection of PDGFRalpha-Fc fragments,
      inhibit the migration of mesoderm cells after their ingression through the
      primitive streak. siRNA-mediated downregulation of Pdgfa expression in the
      epiblast on one side of the streak strongly blocks the migration of mesoderm
      cells into that side. Beads soaked in PDGFA elicit a directional attractive
      movement response in mesoderm cells, showing that PDGFA can provide directional
      information. Surprisingly, however, PDGF signalling is also required for
      directional movement towards other attractants, such as FGF4. PDGF signalling
      controls N-cadherin expression on mesoderm cells, which is required for efficient
      migration. PDGF signalling activates the PI3 kinase signalling pathway in vivo
      and activation of this pathway is required for proper N-cadherin expression.

PMID- 18832397
TI  - Notch signaling is required for the maintenance of enteric neural crest
      progenitors.
AB  - Notch signaling is involved in neurogenesis, including that of the peripheral
      nervous system as derived from neural crest cells (NCCs). However, it remains
      unclear which step is regulated by this signaling. To address this question, we
      took advantage of the Cre-loxP system to specifically eliminate the protein O
      fucosyltransferase 1 (Pofut1) gene, which is a core component of Notch signaling,
      in NCCs. NCC-specific Pofut1-knockout mice died within 1 day of birth,
      accompanied by a defect of enteric nervous system (ENS) development. These
      embryos showed a reduction in enteric neural crest cells (ENCCs) resulting from
      premature neurogenesis. We found that Sox10 expression, which is normally
      maintained in ENCC progenitors, was decreased in Pofut1-null ENCCs. By contrast,
      the number of ENCCs that expressed Mash1, a potent repressor of Sox10, was
      increased in the Pofut1-null mouse. Given that Mash1 is suppressed via the Notch
      signaling pathway, we propose a model in which ENCCs have a cell-autonomous
      differentiating program for neurons as reflected in the expression of Mash1, and
      in which Notch signaling is required for the maintenance of ENS progenitors by
      attenuating this cell-autonomous program via the suppression of Mash1.

PMID- 18832398
TI  - Auscultation in the diagnosis of respiratory disease in the 21st century.

PMID- 18832399
TI  - How to measure severity of mitral regurgitation.

PMID- 18832400
TI  - Prognostic and predictive factors in colorectal cancer.
AB  - Prognostication of newly diagnosed colorectal cancer (CRC) predominantly relies
      on stage as defined by the UICC-TNM and American Joint Committee on Cancer
      classifications. Tumour extent, lymph node status, tumour grade and the
      assessment of lymphatic and venous invasion are still the most important
      morphological prognostic factors. Evidence suggests that tumour budding and
      tumour border configuration are important, additional histological parameters but
      are not regarded as essential in prognosis. Although several molecular features,
      such as LOH18q and TP53 mutation analysis, have shown promising results in terms
      of their prognostic value, the American Society of Clinical Oncology Tumor
      Markers Expert Panel does not currently recommend their use in routine practice.
      cDNA-microarray, PCR and fluorescence in situ hybridisation are now frequently
      used to identity potential prognostic indicators in CRC, but the applicability of
      these methods in routine use is likely to have limited impact. Reliable
      prognostic markers identified by immunohistochemical protein profiling have yet
      to be established. Randomisation of data sets, assessment of interobserver
      variability for protein markers and scoring systems, as well as the use of
      receiver operating characteristic curve analysis in combination with multimarker
      phenotype analysis of several different markers may be an effective tactical
      approach to increase the value of immunohistochemical findings. This article
      reviews the well established and additional prognostic factors in CRC and
      explores the contribution of molecular studies to the prognostication of patients
      with this disease. Additionally, an approach to improve the prognostic value of
      immunohistochemical protein markers is proposed.

PMID- 18832401
TI  - Early neurological deterioration in acute ischaemic stroke: predictors,
      mechanisms and management.
AB  - Early neurological deterioration (END) in acute ischaemic stroke is a common
      event. The underlying mechanisms are heterogeneous. The clinical predictors of
      END include severity of the initial stroke, large vessel occlusion, diabetes
      mellitus, hypotension, and atrial fibrillation. Serial observations and detailed
      assessment by the trained staff in specialised stroke units are key to the
      successful management of these patients. Advances in brain and vascular imaging
      have provided insight into the underlying mechanisms, enabling clinicians to use
      preventative and therapeutic interventions specifically targeted at them, though
      several questions still remain unanswered. END has potentially serious
      consequences on the short term (morbidity and death) and long term (recovery from
      stroke) outcomes for the patient. Therefore, attempts to prevent and treat END
      should be made promptly and aggressively.

PMID- 18832402
TI  - Transcendental meditation and hypertension.

PMID- 18832403
TI  - Common acute oncological emergencies: diagnosis, investigation and management.
AB  - In the UK an aging population is resulting in more people being diagnosed with
      cancer, and an increasing number of treatment options means that many patients
      live significantly longer with their disease. It is anticipated therefore that an
      increasing number of patients will present to primary and secondary care with
      acute complications of cancer, or the treatment thereof. Many doctors have
      limited experience in managing patients with cancer and acute oncological
      emergencies. This article reviews the diagnosis and management of four common
      oncological emergencies: febrile neutropenia, metastatic spinal cord compression,
      superior vena cava obstruction, and malignancy associated hypercalcaemia. It is
      vital to recognise these conditions, as failure to implement immediate and
      appropriate treatment may result in significant morbidity or death.

PMID- 18832404
TI  - Cross-sectional survey of disturbed behaviour in patients in general hospitals in
      Leeds.
AB  - AIM: To describe the prevalence and nature of disturbed behaviour, in the general
      hospital setting. METHOD: A cross-sectional survey was conducted, from July to
      October 2006, in all adult inpatient wards within the six general hospitals in
      Leeds of patients presenting with disturbed behaviour in the preceding 7 days.
      Disturbed behaviour was defined as behaviour interfering with care of the patient
      or with that of other patients, or behaviour that placed the patient, the staff
      or others at risk. Anonymised data were collected using a semi-structured
      questionnaire. RESULTS: All of the 87 hospital wards were studied, containing a
      total of 1773 beds. 42 male and 26 female patients (n = 68) were identified by
      nursing staff as patients with disturbed behaviour in the time period covered,
      with 33 patients being <or=65 years of age and 35 being elderly (>65 years of
      age). An almost equal proportion of the younger and older patient groups placed
      themselves or others at risk. In the majority of cases, aggressive behaviour by
      patients was directed towards staff rather than other patients. 60 patients
      required additional staff time due to the disturbed behaviour, 34 required
      additional medication, and 22 patients were referred to liaison psychiatry.
      CONCLUSIONS: Disturbed behaviour presents in the general hospital in less than 4%
      of patients, both above and below the age of 65 years, but consumes a
      disproportionate amount of resources. Responses required to manage this include
      additional medication, additional staff time or other interventions. The quantity
      and nature of disturbed behaviour in the general hospital have implications for
      effective service provision and development.

PMID- 18832405
TI  - Phasic characteristics of inspiratory crackles of bacterial and atypical
      pneumonia.
AB  - BACKGROUND: No known physical findings are available to differentiate between
      bacterial pneumonia (BP) and atypical pneumonia (AP) in patients with community
      acquired pneumonia (CAP). OBJECTIVE: To evaluate the possible differences in
      phasic characteristics of inspiratory crackles between BP and AP in patients with
      CAP. METHODS: Retrospective chart reviews were conducted to obtain phasic
      characteristics of inspiratory crackles (early, early-to-mid, late and pan
      inspiratory crackles) in AP and BP groups in a community teaching hospital in
      Japan (n = 183). RESULTS: 100 patients with BP and 83 patients with AP were
      evaluated. Patients with BP were significantly more likely to present with pan
      inspiratory crackles (49 (49.0) vs 5 (6.0); p<0.0001), whereas patients with AP
      were more likely to present with late inspiratory crackles (28 (33.7) vs 9 (9.0);
      p<0.0001) (mean (SD)). Among pneumonia patients with audible crackles, the
      sensitivity and specificity of pan-inspiratory crackles for BP were 83.1% and
      85.7%, respectively, and the sensitivity and specificity of late inspiratory
      crackles for AP were 80.0% and 84.7%, respectively. DISCUSSION: In patients with
      CAP and audible crackles, phasic characteristics of inspiratory crackles may be
      used to distinguish AP from BP. Prospective studies are needed to confirm these
      findings.

PMID- 18832406
TI  - Changing education to improve patient care.
AB  - Health professionals need competencies in improvement skills if they are to
      contribute usefully to improving patient care. Medical education programmes in
      the USA have not systematically taught improvement skills to residents
      (registrars in the UK). The Accreditation Council for Graduate Medical Education
      (ACGME) has recently developed and begun to deploy a competency based model for
      accreditation that may encourage the development of improvement skills by the 100
      000 residents in accredited programmes. Six competencies have been identified for
      all physicians, independent of specialty, and measurement tools for these
      competencies have been described. This model may be applicable to other
      healthcare professions. This paper explores patterns that inhibit efforts to
      change practice and proposes an educational model to provide changes in
      management skills based on trainees' analysis of their own work.

PMID- 18832407
TI  - A case of refractory hypoxaemia.

PMID- 18832408
TI  - Acute thyroiditis due to septic emboli derived from infective endocarditis.
AB  - Acute infectious thyroiditis is a rare condition of the thyroid gland, most often
      arising in children with congenital conditions connecting the thyroid directly to
      the oropharynx, such as a piriform fistula or thyroglossal duct. We report a case
      of acute thyroiditis due to septic emboli derived from infective endocarditis.

PMID- 18832409
TI  - Thinking in three dimensions.

PMID- 18832410
TI  - Identifying famines.

PMID- 18832411
TI  - Diagnosing child abuse.

PMID- 18832412
TI  - Patterns of skeletal fractures in child abuse: systematic review.
AB  - OBJECTIVES: To systematically review published studies to identify the
      characteristics that distinguish fractures in children resulting from abuse and
      those not resulting from abuse, and to calculate a probability of abuse for
      individual fracture types. DESIGN: Systematic review. DATA SOURCES: All language
      literature search of Medline, Medline in Process, Embase, Assia, Caredata, Child
      Data, CINAHL, ISI Proceedings, Sciences Citation, Social Science Citation Index,
      SIGLE, Scopus, TRIP, and Social Care Online for original study articles,
      references, textbooks, and conference abstracts until May 2007. STUDY SELECTION:
      Comparative studies of fracture at different bony sites, sustained in physical
      abuse and from other causes in children <18 years old were included. Review
      articles, expert opinion, postmortem studies, and studies in adults were
      excluded. Data extraction and synthesis Each study had two independent reviews
      (three if disputed) by specialist reviewers including paediatricians, paediatric
      radiologists, orthopaedic surgeons, and named nurses in child protection. Each
      study was critically appraised by using data extraction sheets, critical
      appraisal forms, and evidence sheets based on NHS Centre for Reviews and
      Dissemination guidance. Meta-analysis was done where possible. A random effects
      model was fitted to account for the heterogeneity between studies. RESULTS: In
      total, 32 studies were included. Fractures resulting from abuse were recorded
      throughout the skeletal system, most commonly in infants (<1 year) and toddlers
      (between 1 and 3 years old). Multiple fractures were more common in cases of
      abuse. Once major trauma was excluded, rib fractures had the highest probability
      for abuse (0.71, 95% confidence interval 0.42 to 0.91). The probability of abuse
      given a humeral fracture lay between 0.48 (0.06 to 0.94) and 0.54 (0.20 to 0.88),
      depending on the definition of abuse used. Analysis of fracture type showed that
      supracondylar humeral fractures were less likely to be inflicted. For femoral
      fractures, the probability was between 0.28 (0.15 to 0.44) and 0.43 (0.32 to
      0.54), depending on the definition of abuse used, and the developmental stage of
      the child was an important discriminator. The probability for skull fractures was
      0.30 (0.19 to 0.46); the most common fractures in abuse and non-abuse were linear
      fractures. Insufficient comparative studies were available to allow calculation
      of a probability of abuse for other fracture types. CONCLUSION: When infants and
      toddlers present with a fracture in the absence of a confirmed cause, physical
      abuse should be considered as a potential cause. No fracture, on its own, can
      distinguish an abusive from a non-abusive cause. During the assessment of
      individual fractures, the site, fracture type, and developmental stage of the
      child can help to determine the likelihood of abuse. The number of high quality
      comparative research studies in this field is limited, and further prospective
      epidemiology is indicated.

PMID- 18832413
TI  - Retrospective determination of whether famine existed in Niger, 2005: two stage
      cluster survey.
AB  - OBJECTIVE: To apply the famine scale by Howe and Devereux to the situation in
      Niger, west Africa, in 2005 to retrospectively determine whether famine existed.
      DESIGN: Two stage cluster survey. SETTING: Survey of households in each of
      Niger's eight regions. PARTICIPANTS: 4003 households. MAIN OUTCOME MEASURES:
      Crude mortality, mortality in children under 5, and the proportion of caregivers
      both nationally and regionally adopting coping strategies to deal with
      insufficient food needs. RESULTS: The estimated national crude mortality rate was
      0.4 (0.4 to 0.5) deaths per 10,000 per day and under 5 mortality rate was 1.7
      (1.4 to 1.9) deaths per 10,000 per day. Nationally, 22.3% (95% confidence
      interval 19.9% to 24.8%) of caregivers of under 5s did not resort to any coping
      strategies to deal with insufficient food needs. Reversible coping strategies
      were, however, used by 5.8% (4.7% to 7.0%) of caregivers, whereas 49.4% (46.9% to
      51.8%) relied on irreversible coping strategies and 22.6% (20.0% to 25.4%) on
      survival strategies. CONCLUSION: On the basis of the famine scale proposed by
      Howe and Devereux, most regions in Niger experienced food crisis conditions and
      some areas approached famine proportions.

PMID- 18832414
TI  - Medically certified sickness absence.

PMID- 18832415
TI  - Diagnosis-specific sickness absence as a predictor of mortality: the Whitehall II
      prospective cohort study.
AB  - OBJECTIVE: To investigate whether knowing the diagnosis for sickness absence
      improves prediction of mortality. DESIGN: Prospective cohort study established in
      1985-8. Sickness absence records including diagnoses were obtained from
      computerised registers. SETTING: 20 civil service departments in London.
      PARTICIPANTS: 6478 civil servants aged 35-55 years. MAIN OUTCOME MEASURES: All
      cause, cardiovascular, and cancer mortality until 2004, average follow-up 13
      years. RESULTS: After adjustment for age, sex, and employment grade, employees
      who had one or more medically certified spells of sickness absence (>7 days) in a
      three year period had a mortality 1.7 (95% CI 1.3 to 2.1) times greater than
      those with no medically certified spells. Inclusion of diagnoses improved the
      prediction of all cause mortality (P=0.03). The hazard ratio for mortality was
      4.7 (2.6 to 8.5) for absences with circulatory disease diagnoses, 2.2 (1.4 to
      3.3) for surgical operations, and 1.9 (1.2 to 3.1) for psychiatric diagnoses.
      Psychiatric absences were also predictive of cancer mortality (2.5 (1.3 to 4.7)).
      Associations of infectious, respiratory, and injury absences with overall
      mortality were less marked (hazard ratios from 1.5 to 1.7), and there was no
      association between musculoskeletal absences and mortality. CONCLUSIONS: Major
      diagnoses for medically certified absences were associated with increased
      mortality, with the exception of musculoskeletal disease. Data on sickness
      absence diagnoses may provide useful information to identify groups with
      increased health risk and a need for targeted interventions.

PMID- 18832416
TI  - Should we use regulation to demand improved public health outcomes from industry?
      Yes.

PMID- 18832417
TI  - Should we use regulation to demand improved public health outcomes from industry?
      No.

PMID- 18832418
TI  - Global exhibition will highlight drug resistant TB.

PMID- 18832419
TI  - Contribution of respiratory muscle blood flow to exercise-induced diaphragmatic
      fatigue in trained cyclists.
AB  - We investigated whether the greater degree of exercise-induced diaphragmatic
      fatigue previously reported in highly trained athletes in hypoxia (compared with
      normoxia) could have a contribution from limited respiratory muscle blood flow.
      Seven trained cyclists completed three constant load 5 min exercise tests at
      inspired O(2) fractions (FIO2) of 0.13, 0.21 and 1.00 in balanced order. Work
      rates were selected to produce the same tidal volume, breathing frequency and
      respiratory muscle load at each FIO2 (63 +/- 1, 78 +/- 1 and 87 +/- 1% of
      normoxic maximal work rate, respectively). Intercostals and quadriceps muscle
      blood flow (IMBF and QMBF, respectively) were measured by near-infrared
      spectroscopy over the left 7th intercostal space and the left vastus lateralis
      muscle, respectively, using indocyanine green dye. The mean pressure time product
      of the diaphragm and the work of breathing did not differ across the three
      exercise tests. After hypoxic exercise, twitch transdiaphragmatic pressure fell
      by 33.3 +/- 4.8%, significantly (P < 0.05) more than after both normoxic (25.6 +/
      3.5% reduction) and hyperoxic (26.6 +/- 3.3% reduction) exercise, confirming
      greater fatigue in hypoxia. Despite lower leg power output in hypoxia, neither
      cardiac output nor QMBF (27.6 +/- 1.2 l min(-1) and 100.4 +/- 8.7 ml (100 ml)(-1)
      min(-1), respectively) were significantly different compared with normoxia (28.4
      +/- 1.9 l min(-1) and 94.4 +/- 5.2 ml (100 ml)(-1) min(-1), respectively) and
      hyperoxia (27.8 +/- 1.6 l min(-1) and 95.1 +/- 7.8 ml (100 ml)(-1) min(-1),
      respectively). Neither IMBF was different across hypoxia, normoxia and hyperoxia
      (53.6 +/- 8.5, 49.9 +/- 5.9 and 52.9 +/- 5.9 ml (100 ml)(-1) min(-1),
      respectively). We conclude that when respiratory muscle energy requirement is not
      different between normoxia and hypoxia, diaphragmatic fatigue is greater in
      hypoxia as intercostal muscle blood flow is not increased (compared with
      normoxia) to compensate for the reduction in PaO2, thus further compromising O(2)
      supply to the respiratory muscles.

PMID- 18832420
TI  - STIM1-Orai1 interactions and Orai1 conformational changes revealed by live-cell
      FRET microscopy.
AB  - Ca(2+) entry through store-operated Ca(2+) release-activated Ca(2+) (CRAC)
      channels initiates key functions such as gene expression and exocytosis of
      inflammatory mediators. Activation of CRAC channels by store depletion involves
      the redistribution of the ER Ca(2+) sensor, stromal interaction molecule 1
      (STIM1), to peripheral sites where it co-clusters with the CRAC channel subunit,
      Orai1. However, how STIM1 communicates with the CRAC channel and initiates the
      subsequent events culminating in channel opening is unclear. Here, we show that
      redistribution of STIM1 and Orai1 occurs in parallel with a pronounced increase
      in fluorescence resonance energy transfer (FRET) between STIM1 and Orai1,
      supporting the idea that activation of CRAC channels occurs through physical
      interactions with STIM1. Co-expression of Orai1-CFP and Orai1-YFP results in a
      high degree of FRET in resting cells, indicating that Orai1 exists as a multimer.
      However, store depletion triggers molecular rearrangements in Orai1 resulting in
      a decline in Orai1-Orai1 FRET. The decline in Orai1-Orai1 FRET is not seen in the
      absence of STIM1 co-expression and is abolished in Orai1 mutants with impaired
      STIM1 interaction. Both the STIM1-Orai1 interaction as well as the molecular
      rearrangements in Orai1 are altered by two powerful modulators of CRAC channel
      activity: extracellular Ca(2+) and 2-APB. These studies identify a STIM1
      dependent conformational change in Orai1 during the activation of CRAC channels
      and reveal that STIM1-Orai1 interaction and the downstream Orai1 conformational
      change can be independently modulated to fine-tune CRAC channel activity.

PMID- 18832421
TI  - GABA transporter 1 tunes GABAergic synaptic transmission at output neurons of the
      mouse neostriatum.
AB  - GABAergic medium-sized striatal output neurons (SONs) provide the principal
      output for the neostriatum. In vitro and in vivo data indicate that spike
      discharge of SONs is tightly controlled by effective synaptic inhibition.
      Although phasic GABAergic transmission critically depends on ambient GABA levels,
      the role of GABA transporters (GATs) in neostriatal GABAergic synaptic
      transmission is largely unknown. In the present study we aimed at elucidating the
      role of GAT-1 in the developing mouse neostriatum (postnatal day (P) 7-34). We
      recorded GABAergic postsynaptic currents (PSCs) using the whole-cell patch-clamp
      technique. Based on the effects of NO-711, a specific GAT-1 blocker, we
      demonstrate that GAT-1 is operative at this age and influences GABAergic synaptic
      transmission by presynaptic and postsynaptic mechanisms. Presynaptic GABA(B)R
      mediated suppression of GABA release was found to be functional at all ages
      tested; however, there was no evidence for persistent GABA(B)R activity under
      control conditions, unless GAT-1 was blocked (P12-34). In addition, whereas no
      tonic GABA(A)R-mediated conductances were detected in SONs until P14, application
      of a specific GABA(A)R antagonist caused distinct tonic outward currents later in
      development (P19-34). In the presence of NO-711, tonic GABA(A)R-mediated currents
      were also observed at P7-14 and were dramatically increased at more mature
      stages. Furthermore, GAT-1 block reduced the median amplitude of GABAergic
      miniature PSCs indicating a decrease in quantal size. We conclude that in the
      murine neostriatum GAT-1 operates in a net uptake mode. It prevents the
      persistent activation of presynaptic GABA(B)Rs (P12-34) and prevents (P7-14) or
      reduces (P19-34) tonic postsynaptic GABA(A)R activity.

PMID- 18832422
TI  - Hypoosmotic- and pressure-induced membrane stretch activate TRPC5 channels.
AB  - Transient receptor potential (TRP) channels mediate a wide array of sensory
      functions. We investigated the role of TRPC5, a poorly characterized channel
      widely expressed in the central and peripheral nervous system, as a potential
      osmosensory protein. Here we show that hypoosmotic stimulation activates TRPC5
      channels resulting in a large calcium influx. The response to osmotically induced
      membrane stretch is blocked by GsMTx-4, an inhibitor of stretch activated ion
      channels. Direct hypoosmotic activation of TRPC5 is independent of phospholipase
      C function. However, the osmotic response is inhibited in a cell line in which
      PIP(2) levels are reduced by regulated overexpression of a lipid phosphatase. The
      response was restored by increasing intracellular PIP(2) levels through the patch
      pipette. The mechano-sensitivity of the channel was probed in the whole-cell
      configuration by application of steps of positive pressure through the patch
      pipette. Pressure-induced membrane stretch also activated TRPC5 channels,
      suggesting its role as a transducer of osmo-mechanical stimuli. We also
      demonstrated the expression of TRPC5 in sensory neurones which together with the
      osmo-mechanical characteristics of TRPC5 channels suggest its putative role in
      mechanosensory transduction events.

PMID- 18832423
TI  - Altered expression of TRPV1 and sensitivity to capsaicin in pulmonary myelinated
      afferents following chronic airway inflammation in the rat.
AB  - Vagal pulmonary myelinated afferents are normally not activated by capsaicin, a
      selective agonist of transient receptor potential vanilloid type 1 (TRPV1)
      receptors. This study was carried out to investigate whether the expression of
      TRPV1 in these afferents is altered when chronic airway inflammation is induced
      by ovalbumin (Ova) sensitization. Two groups of Brown-Norway rats (sensitized and
      control) were exposed to aerosolized Ova and vehicle, respectively, 3 days per
      week for 3 weeks. After the C-fibre conduction in both vagus nerves was blocked,
      right-atrial injection of capsaicin elicited augmented breaths in sensitized rats
      breathing spontaneously, but not in control rats, indicating a stimulation of
      rapidly adapting receptors (RARs) by capsaicin. Single-unit fibre activities of
      RARs and slow adapting receptors (SARs), identified by their firing behaviour and
      adaptation indexes in response to lung inflation, were recorded in anaesthetized,
      vagotomized and artificially ventilated rats. Capsaicin injection evoked either
      negligible or no response in both RARs and SARs of control rats. However, in
      striking contrast, the same dose of capsaicin evoked an immediate stimulatory
      effect on these myelinated afferents in sensitized rats. Furthermore, the
      immunohistochemistry experiments showed that there was a significant increase in
      the proportion of TRPV1-expressing pulmonary neurones in nodose ganglia of
      sensitized rats; this increase in TRPV1 expression was found mainly in
      neurofilament-positive (myelinated) neurones. In conclusion, allergen-induced
      airway inflammation clearly elevated capsaicin sensitivity in myelinated
      pulmonary afferents, which probably resulted from an increased expression of
      TRPV1 in these sensory nerves.

PMID- 18832424
TI  - Distinct expressions of contrast gain control in parallel synaptic pathways
      converging on a retinal ganglion cell.
AB  - Visual neurons adapt to increases in stimulus contrast by reducing their response
      sensitivity and decreasing their integration time, a collective process known as
      'contrast gain control.' In retinal ganglion cells, gain control arises at two
      stages: an intrinsic mechanism related to spike generation, and a synaptic
      mechanism in retinal pathways. Here, we tested whether gain control is expressed
      similarly by three synaptic pathways that converge on an OFF alpha/Y-type
      ganglion cell: excitatory inputs driven by OFF cone bipolar cells; inhibitory
      inputs driven by ON cone bipolar cells; and inhibitory inputs driven by rod
      bipolar cells. We made whole-cell recordings of membrane current in guinea pig
      ganglion cells in vitro. At high contrast, OFF bipolar cell-mediated excitatory
      input reduced gain and shortened integration time. Inhibitory input was measured
      by clamping voltage near 0 mV or by recording in the presence of ionotropic
      glutamate receptor (iGluR) antagonists to isolate the following circuit: cone -->
      ON cone bipolar cell --> AII amacrine cell --> OFF ganglion cell. At high
      contrast, this input reduced gain with no effect on integration time. Mean
      luminance was reduced 1000-fold to recruit the rod bipolar pathway: rod --> rod
      bipolar cell --> AII cell --> OFF ganglion cell. The spiking response, measured
      with loose-patch recording, adapted despite essentially no gain control in
      synaptic currents. Thus, cone bipolar-driven pathways adapt differently, with
      kinetic effects confined to the excitatory OFF pathway. The ON bipolar-mediated
      inhibition reduced gain at high contrast by a mechanism that did not require an
      iGluR. Under rod bipolar-driven conditions, ganglion cell firing showed gain
      control that was explained primarily by an intrinsic property.

PMID- 18832425
TI  - Autonomous initiation and propagation of action potentials in neurons of the
      subthalamic nucleus.
AB  - The activity of the subthalamic nucleus (STN) is intimately related to movement
      and is generated, in part, by voltage-dependent Na(+) (Na(v)) channels that drive
      autonomous firing. In order to determine the principles underlying the initiation
      and propagation of action potentials in STN neurons, 2-photon laser scanning
      microscopy was used to guide tight-seal whole-cell somatic and loose-seal cell
      attached axonal/dendritic patch-clamp recordings and compartment-selective ion
      channel manipulation in rat brain slices. Action potentials were first detected
      in a region that corresponded most closely to the unmyelinated axon initial
      segment, as defined by Golgi and ankyrin G labelling. Following initiation,
      action potentials propagated reliably into axonal and somatodendritic
      compartments with conduction velocities of approximately 5 m s(-1) and
      approximately 0.7 m s(-1), respectively. Action potentials generated by neurons
      with axons truncated within or beyond the axon initial segment were not
      significantly different. However, axon initial segment and somatic but not
      dendritic or more distal axonal application of low [Na(+)] ACSF or the selective
      Na(v) channel blocker tetrodotoxin consistently depolarized action potential
      threshold. Finally, somatodendritic but not axonal application of GABA evoked
      large, rapid inhibitory currents in concordance with electron microscopic
      analyses, which revealed that the somatodendritic compartment was the principal
      target of putative inhibitory inputs. Together the data are consistent with the
      conclusions that in STN neurons the axon initial segment and soma express an
      excess of Na(v) channels for the generation of autonomous activity, while
      synaptic activation of somatodendritic GABA(A) receptors regulates the axonal
      initiation of action potentials.

PMID- 18832426
TI  - A limited contribution of Ca2+ current facilitation to paired-pulse facilitation
      of transmitter release at the rat calyx of Held.
AB  - Recent studies have suggested that transmitter release facilitation at synapses
      is largely mediated by presynaptic Ca(2+) current facilitation, but the exact
      contribution of Ca(2+) current facilitation has not been determined
      quantitatively. Here, we determine the contribution of Ca(2+) current
      facilitation, and of an increase in the residual free Ca(2+) concentration
      ([Ca(2+)](i)) in the nerve terminal, to paired-pulse facilitation of transmitter
      release at the calyx of Held. Under conditions of low release probability imposed
      by brief presynaptic voltage-clamp steps, transmitter release facilitation at
      short interstimulus intervals (4 ms) was 227 +/- 31% of control, Ca(2+) current
      facilitation was 113 +/- 4% of control, and the peak residual [Ca(2+)](i) was 252
      +/- 18 nm over baseline. By inferring the 'local' [Ca(2+)](i) transients that
      drive transmitter release during these voltage-clamp stimuli with the help of a
      kinetic release model, we estimate that Ca(2+) current facilitation contributes
      to approximately 40% to paired-pulse facilitation of transmitter release. The
      remaining component of facilitation strongly depends on the build-up, and on the
      decay of the residual free [Ca(2+)](i), but cannot be explained by linear
      summation of the residual free [Ca(2+)](i), and the back-calculated 'local'
      [Ca(2+)](i) signal, which only accounts for approximately 10% of the total
      release facilitation. Further voltage-clamp experiments designed to compensate
      for Ca(2+) current facilitation demonstrated that about half of the observed
      transmitter release facilitation remains in the absence of Ca(2+) current
      facilitation. Our results indicate that paired-pulse facilitation of transmitter
      release at the calyx of Held is driven by at least two distinct mechanisms:
      Ca(2+) current facilitation, and a mechanism independent of Ca(2+) current
      facilitation that closely tracks the time course of residual free [Ca(2+)](i).

PMID- 18832427
TI  - The pharmacokinetics of standard antidepressants with aripiprazole as adjunctive
      therapy: studies in healthy subjects and in patients with major depressive
      disorder.
AB  - Possible effects of the atypical antipsychotic aripiprazole on the
      pharmacokinetics of standard antidepressant therapies (ADTs) were assessed in two
      open-label, non-randomised studies in healthy subjects (Studies 1 and 2) and two
      placebo-controlled studies in patients with major depressive disorder (MDD)
      (Studies 3 and 4). Healthy subjects received venlafaxine 75 mg/day (Study 1; N =
      38) or escitalopram 10 mg/ day (Study 2; N = 25) with the addition of
      aripiprazole 10-20 mg/day (10 mg/day fixed dose in Study 2) for 14 days. Patients
      with MDD (N = 498; Studies 3 and 4) received escitalopram (10-20 mg/day),
      fluoxetine (20-40 mg/day), paroxetine controlled-release (37.5-50 mg/day),
      sertraline (100-150 mg/day) or venlafaxine extended-release (150-225 mg/day) for
      8 weeks plus placebo. Incomplete responders were randomised (1:1) to placebo or
      adjunctive aripiprazole 2-20 mg/day. Blood samples were collected for
      pharmacokinetic analysis of ADTs. Plasma concentration-time data from Studies 3
      and 4 were combined for statistical analysis. In healthy subjects, point
      estimates [90% CI] for the ratios of geometric means of C( max) (venlafaxine
      1.148 [1.083-1.217]; escitalopram 1.04 [0.99-1.09]) and AUC(TAU) (venlafaxine
      1.183 [1.130-1.238]; escitalopram 1.07 [1.04-1.11]) indicated no meaningful
      increase in ADT exposure in the presence of aripiprazole. In patients, point
      estimates for mean plasma concentration ratios indicated no substantial effect of
      aripiprazole on any ADT escitalopram 0.970 [0.911-1.033], fluoxetine 1.177 [1.049
      1.321], paroxetine 0.730 [0.598-0.892], sertraline 0.958 [0.887-1.035] or
      venlafaxine 0.966 [0.887-1.051]. Aripiprazole had no meaningful effects on the
      pharmacokinetics of standard ADTs in either healthy subjects or patients with
      MDD.

PMID- 18832428
TI  - Pindolol augmentation of serotonin reuptake inhibitors for the treatment of
      depressive disorder: a systematic review.
AB  - Adding pindolol to serotonergic antidepressant treatment offers a potential
      strategy for producing a more rapid onset of action and an enhanced
      antidepressant effect. This review investigated whether pindolol enhances the
      efficacy of serotonergic antidepressant treatment in adult patients with
      depressive disorders at sequential time points up to 6 weeks. SEARCH STRATEGY:
      Cochrane Collaboration Depression, Anxiety and Neurosis-Controlled Trials
      Register plus unpublished trial data. STUDY SELECTION: Randomised trials
      including depressed patients, comparing serotonergic antidepressants + pindolol
      with serotonergic antidepressants + placebo and using depressive symptom clinical
      outcomes scales. DATA EXTRACTION: Clinical response at time points up to 6 weeks
      as defined by >50% depression scale score reduction was extracted for each trial
      as possible. Eleven studies were identified including unpublished data. The
      pooled odds ratios for dichotomous response to treatment at time points from 1 to
      6 weeks were 2.39 (95% CI 1.40-4.06), 2.39 (1.74-3.29), 1.94 (1.46-2.58), 1.59
      (1.16-2.18), 1.42 (0.87-2.31) and 1.28 (0.91-1.81). Time-to-event analysis showed
      a greater response with pindolol augmentation versus placebo (P = 0.04). There
      was significant heterogeneity between studies at some time points. Dropout rates
      did not significantly differ between treatment arms. This review suggests an
      overall beneficial clinical effect of pindolol augmentation, most clearly up to 4
      weeks of treatment.

PMID- 18832429
TI  - Ecstasy (MDMA) and high prevalence psychiatric symptomatology: somatic anxiety
      symptoms are associated with polydrug, not ecstasy, use.
AB  - Although previous studies have examined anxiety and depression in ecstasy (+/-3,4
      methylenedioxymethamphetamine; MDMA) users, it remains unclear whether symptoms
      are associated specifically with ecstasy or with polydrug use in general. We
      compared mean symptomatology and clinically significant symptoms in 45 ecstasy
      polydrug, 48 cannabis polydrug and 40 legal drug users, who completed
      standardised self-report anxiety and depression symptom measures. We further
      examined whether group differences were secondary to increased somatic symptom
      reporting, which may reflect acute/subacute drug effects. Anxiety and depression
      scores were higher in polydrug than legal drug users, with no difference between
      ecstasy and cannabis groups. There was no difference in numbers meeting criteria
      for clinically significant depression or 'moderate' or 'severe' anxiety, but the
      polydrug group contained more individuals reporting at least 'mild' anxiety
      symptoms than the legal drug control. Multivariate analyses indicated that
      anxiety alone was sufficient to discriminate groups. Polydrug users reported more
      somatic anxiety symptoms than legal drug users, but endorsed equivalent numbers
      of non-somatic symptoms. High prevalence psychiatric symptomatology in ecstasy
      polydrug users may be associated with polydrug rather than ecstasy use. Higher
      ratings in polydrug users appear to be secondary to increased somatic symptom
      reporting, suggesting possible impacts of drug effects on symptom endorsement.

PMID- 18832430
TI  - Propranolol transiently inhibits reinstatement of nicotine-seeking behaviour in
      rats.
AB  - Noradrenergic transmission has been implicated in the affective component of
      relapse to tobacco smoking. Evidence in human and laboratory animals showed that
      smoking or nicotine administration may cause changes of the noradrenergic system
      resulting in hyperactivity in this system after cessation. It has been
      hypothesised that the anti-adrenergic beta-blocker propranolol may decrease
      affective activation and arousal observed during drug withdrawal or cue-induced
      relapse. The aim of the present work was to test the effects of propranolol pre
      treatment in a rat model of nicotine cue-induced relapse to nicotine seeking. We
      also tested the effects of propranolol on food cue-induced reinstatement of food
      seeking in rats trained on food self-administration. Propranolol transiently
      inhibited nicotine cue-induced reinstatement. The inhibitory effect of
      propranolol reached a peak after 30 min from the beginning of the reinstatement
      session and then it declined until it was completely absent at the end of the 3-h
      session. This inhibitory effect of propranolol was not observed when the drug was
      tested versus reinstatement with food cues. The present study suggests a weak
      effect of propranolol to counteract nicotine cue-induced reinstatement of
      nicotine seeking. Therefore, these findings do not support a potential use of
      propranolol for prevention of smoking relapse.

PMID- 18832431
TI  - A psychopharmacological treatment algorithm for generalised anxiety disorder
      (GAD).
AB  - Generalised anxiety disorder (GAD) is defined as excessive and uncontrollable
      worry and anxiety about everyday life situations. It is a chronic disorder, and
      is associated with substantial somatisation, high rates of comorbid depression
      and other anxiety disorders, and significant disability. The evidence base for
      pharmacotherapy and psychotherapy has continued to grow, and a wide range of drug
      choices for GAD now exists. Current guidelines for GAD generally restrict
      themselves to presentation of the evidence for various treatments, which, as a
      result, generally do not offer detailed discussion or recommendation of
      strategies beyond the first level of treatment, or take into account the
      individual circumstances of the patient. Thus, there is a lack of algorithm-based
      treatment guidelines for GAD. Our aim is, therefore, to present an algorithm for
      the psychopharmacologic management of GAD, intended for all clinicians who treat
      patients with GAD, where issues of pharmacotherapy are under consideration. We
      also hope that these GAD algorithms and other guidelines can help to identify
      high-priority areas that need further study. In this algorithm, we provide a
      sequenced approach to the pharmacotherapy of GAD, taking into account salient
      symptomatology and comorbidity, levels of evidence and extent of response.
      Special issues, including comorbidity, insomnia, suicidality, substance abuse,
      treatment adherence, pregnancy and lactation, cross-cultural issues, use of
      medication in the elderly, psychosocial treatment and dosing issues are also
      addressed.

PMID- 18832432
TI  - Augmenting serotonin neurotransmission with citalopram modulates emotional
      expression decoding but not structural encoding of moderate intensity sad facial
      emotional stimuli: an event-related potential (ERP) investigation.
AB  - Antidepressants targeting the serotonergic system have been shown to modulate
      biases in emotional processing. The effects of serotonergic modulation on the
      temporal course of emotional processing (accruing within milliseconds) are
      unknown. Furthermore, it is unknown how serotonin affects different stages of
      facial emotional processing. The current study investigated the effects of acute
      serotonin augmentation on event-related potential (ERP) measures associated with
      'structural encoding' (N170) and emotion 'expression decoding' (N250 and a late
      slow-wave positive potential [LPP]) of happy and sad facial stimuli, relative to
      neutral facial stimuli. The study was a double-blind, placebo-controlled, cross
      over design, in which 14 healthy male participants completed a facial recognition
      task under two acute treatment conditions: 1) placebo (PLB) and 2) 20 mg
      citalopram (CIT). ERP recording were conducted while subjects viewed neutral,
      happy and sad facial stimuli. Findings indicated that under PLB, the N170 was not
      modulated by valence (happy or sad versus neutral), but the N250 and LPP were
      enhanced for processing happy (relative to neutral) faces. Citalopram had no
      effect on the N170, but it enhanced the LPP for processing sad (relative to
      neutral) faces. These findings suggest that serotonin enhancement has selective
      and temporal effects on emotional face processing, with evidence for modulating
      processes associated with 'expression decoding' but not 'structural encoding'.
      The enhanced cortical response to perception of moderately intense sad facial
      expressions following citalopram administration may relate to the cognitive
      processing of the social relevance or significance of such ambiguous stimuli.

PMID- 18832433
TI  - Low striatal serotonin transporter protein in a human polydrug MDMA (ecstasy)
      user: a case study.
AB  - Evidence that the widely used methamphetamine analog MDMA (3,4
      methylenedioxymethamphetamine, ecstasy) might damage brain serotonin neurones in
      humans is derived from imaging investigations showing variably decreased binding
      of radioligands to the serotonin transporter (SERT), a marker of serotonin
      neurones. However, in humans, it is not known whether low SERT binding reflects
      actual loss of SERT protein itself. As this question can only be answered in post
      mortem brain, we measured protein levels of SERT and that of the rate-limiting
      serotonin-synthesizing enzyme tryptophan hydroxylase (TPH) in autopsied brain of
      a high-dose MDMA user. As compared with control values, SERT protein levels were
      markedly (-48% to -58%) reduced in striatum (caudate, putamen) and occipital
      cortex and less affected (-25%) in frontal and temporal cortices, whereas TPH
      protein was severely decreased in caudate and putamen (-68% and -95%,
      respectively). The magnitude of the striatal SERT protein reduction was greater
      than the SERT binding decrease typically reported in imaging studies. Although
      acknowledging limitations of a case study, these findings extend imaging data
      based on SERT binding and suggest that high-dose MDMA exposure could cause loss
      of two key protein markers of brain serotonin neurones, a finding compatible with
      either physical damage to serotonin neurones or downregulation of components
      therein.

PMID- 18832434
TI  - The effects of single dose anxiolytic medication on the CO2 models of anxiety:
      differentiation of subjective and objective measures.
AB  - This was a double blind, placebo-controlled, 4-way cross-over study in 12 healthy
      volunteer subjects of the acute effects of three drugs each of which are used in
      the clinic to treat some forms of anxiety: propranolol 40 mg, hydroxyzine 25 mg,
      flupentixol 0.5 mg and placebo. Each test session consisted of inhalation of air
      for 20 min, 10-min rest, inhalation of CO2 7.5% for 20 min, 10-min rest, followed
      by a single vital capacity inhalation of 35% CO2. The CO2 7.5% was administered
      at peak drug effect. Subjective effects were measured using Visual Analogue
      Scales (VAS), the Panic Symptom Inventory and the Generalised Anxiety Disorder
      Assessment inventory. Twelve subjects participated (eight men), with a mean age
      of 25.9 years. The expected subjective effects of CO2 were seen and these were
      significantly different from effects of peak air. However, there were no
      statistically significant differences between the drugs or between drugs and
      placebo, indeed there was a trend for some VAS anxiety scores to be higher than
      placebo in the drug groups. There were some significant differences in
      cardiovascular responses to CO2, with propranolol significantly decreasing heart
      rate and flupentixol increasing blood pressure when compared with placebo. The
      lack of subjective anxiolytic actions of the three drugs contrasts with our
      previous findings with acute benzodiazepines and chronic selective serotonin
      reuptake inhibitor administration. It may be that prolonged treatment with these
      agents would be required to show anxiolytic effects, although it may also be that
      their efficacy is insufficient to be demonstrated in this model. The lack of
      anxiolytic actions of propranolol, despite a significant reduction in heart rate,
      is a further support for a central action of CO2 to produce anxiety.

PMID- 18832435
TI  - Hydrogen sulfide inhibits rotenone-induced apoptosis via preservation of
      mitochondrial function.
AB  - Hydrogen sulfide (H(2)S) has been proposed as a novel neuromodulator, which plays
      critical roles in the central nervous system affecting both neurons and glial
      cells. However, its relationship with neurodegenerative diseases is unexplored.
      The present study was undertaken to investigate the effects of H(2)S on cell
      injury induced by rotenone, a commonly used toxin in establishing in vivo and in
      vitro Parkinson's disease (PD) models, in human-derived dopaminergic
      neuroblastoma cell line (SH-SY5Y). We report here that sodium hydrosulfide
      (NaHS), an H(2)S donor, concentration-dependently suppressed rotenone-induced
      cellular injury and apoptotic cell death. NaHS also prevented rotenone-induced
      p38- and c-Jun NH(2)-terminal kinase (JNK)-mitogen-activated protein kinase
      (MAPK) phosphorylation and rotenone-mediated changes in Bcl-2/Bax levels,
      mitochondrial membrane potential (DeltaPsi(m)) dissipation, cytochrome c release,
      caspase-9/3 activation and poly(ADP-ribose) polymerase cleavage. Furthermore, 5
      hydroxydecanoate, a selective blocker of mitochondrial ATP-sensitive potassium
      (mitoK(ATP)) channel, attenuated the protective effects of NaHS against rotenone
      induced cell apoptosis. Thus, we demonstrated for the first time that H(2)S
      inhibited rotenone-induced cell apoptosis via regulation of mitoK(ATP)
      channel/p38- and JNK-MAPK pathway. Our data suggest that H(2)S may have potential
      therapeutic value for neurodegenerative diseases, such as PD.

PMID- 18832436
TI  - Calcineurin inhibitors modulate CXCR3 splice variant expression and mediate renal
      cancer progression.
AB  - Calcineurin inhibitors (CNI) are used to prevent inflammatory diseases and
      allograft rejection. However, little is known about the mechanism(s) underlying
      their ability to promote the development and recurrence of cancer. Recent studies
      suggested that the chemokine receptor CXCR3 may play important roles in
      tumorigenesis. CXCR3 has two splice variants with opposite functions: CXCR3-A
      promotes cell proliferation, and CXCR3-B inhibits cell growth. Here, we explored
      the effects of CNI on the expression and function of CXCR3 splice variants.
      Compared with normal renal tissues and renal epithelial cells, human renal cancer
      tissues and renal cancer cell lines demonstrated higher expression of CXCR3-A and
      markedly lower expression of CXCR3-B. In human renal cancer cells (786-0 and Caki
      1) and renal epithelial cells, CNI markedly downregulated the expression of CXCR3
      B, whereas expression of CXCR3-A was unchanged. This CNI-mediated downregulation
      of CXCR3-B resulted in increased proliferation and migration of renal cancer
      cells; CNI-mediated cell proliferation involved signaling through G(i) proteins,
      perhaps via CXCR3-A. Finally, it was observed that CNI treatment increased the
      growth of human renal tumors in vivo, and the expression of CXCR3-B was
      significantly decreased in these tumors. In summary, these observations suggest
      that CNI may mediate the progression of human renal cancer by downregulating
      CXCR3-B and by promoting proliferative signals, likely through CXCR3-A. Targeting
      CXCR3 splice variants or the signaling pathways downstream of CXCR3 receptors may
      provide a therapeutic strategy for the prevention of CNI-mediated renal cancer
      progression.

PMID- 18832437
TI  - Podocyte-specific loss of functional microRNAs leads to rapid glomerular and
      tubular injury.
AB  - MicroRNAs (miRNAs) are in a class of endogenous, small, noncoding RNAs that exert
      their effects through posttranscriptional repression of specific target mRNAs.
      Although miRNAs have been implicated in the regulation of diverse biologic
      processes, little is known about miRNA function in the kidney. Here, mice lacking
      functional miRNAs in the developing podocyte were generated through podocyte
      specific knockout of Dicer, an enzyme required for the production of mature
      miRNAs (Nphs2-Cre; Dicer(flx/flx)). Podocyte-specific loss of miRNAs resulted in
      significant proteinuria by 2 wk after birth, rapid progression of marked
      glomerular and tubular injury beginning at 3 wk, and death by 4 wk. Expression of
      the slit diaphragm proteins nephrin and podocin was decreased, and expression of
      the transcription factor WT1 was relatively unaffected. To identify miRNA-mRNA
      interactions that contribute to this phenotype, we profiled the glomerular
      expression of miRNAs; three miRNAs expressed in glomeruli were identified: mmu
      miR-23b, mmu-miR-24, and mmu-miR-26a. These results suggest that miRNA function
      is dispensable for the initial development of glomeruli but is critical to
      maintain the glomerular filtration barrier.

PMID- 18832439
TI  - Potential role of bone morphogenetic protein (BMP) signalling as a potential
      therapeutic target for modification of iron balance.

PMID- 18832438
TI  - Loss of vitamin D receptor produces polyuria by increasing thirst.
AB  - Vitamin D receptor (VDR)-null mice develop polyuria, but the underlying mechanism
      remains unknown. In this study, we investigated the relationship between vitamin
      D and homeostasis of water and electrolytes. VDR-null mice had polyuria, but the
      urine osmolarity was normal as a result of high salt excretion. The urinary
      responses to water restriction and to vasopressin were similar between wild-type
      and VDR-null mice, suggesting intact fluid-handling capacity in VDR-null mice.
      Compared with wild-type mice, however, renin and angiotensin II were dramatically
      upregulated in the kidney and brain of VDR-null mice, leading to a marked
      increase in water intake and salt appetite. Angiotensin II-mediated upregulation
      of intestinal NHE3 expression partially explained the increased salt absorption
      and excretion in VDR-null mice. In the brain of VDR-null mice, expression of c
      Fos, which is known to associate with increased water intake, was increased in
      the hypothalamic paraventricular nucleus and the subfornical organ. Treatment
      with an angiotensin II type 1 receptor antagonist normalized water intake,
      urinary volume, and c-Fos expression in VDR-null mice. Furthermore, despite a
      salt-deficient diet to reduce intestinal salt absorption, VDR-null mice still
      maintained the increased water intake and urinary output. Together, these data
      indicate that the polyuria observed in VDR-null mice is not caused by impaired
      renal fluid handling or increased intestinal salt absorption but rather is the
      result of increased water intake induced by the increase in systemic and brain
      angiotensin II.

PMID- 18832440
TI  - Increase in poliomyelitis cases in Nigeria.

PMID- 18832441
TI  - Dispensability of mammalian DNA.
AB  - In the lab, the cis-regulatory network seems to exhibit great functional
      redundancy. Many experiments testing enhancer activity of neighboring cis
      regulatory elements show largely overlapping expression domains. Of recent
      interest, mice in which cis-regulatory ultraconserved elements were knocked out
      showed no obvious phenotype, further suggesting functional redundancy. Here, we
      present a global evolutionary analysis of mammalian conserved nonexonic elements
      (CNEs), and find strong evidence to the contrary. Given a set of CNEs conserved
      between several mammals, we characterize functional dispensability as the
      propensity for the ancestral element to be lost in mammalian species internal to
      the spanned species tree. We show that ultraconserved-like elements are over 300
      fold less likely than neutral DNA to have been lost during rodent evolution. In
      fact, many thousands of noncoding loci under purifying selection display near
      uniform indispensability during mammalian evolution, largely irrespective of
      nucleotide conservation level. These findings suggest that many genomic noncoding
      elements possess functions that contribute noticeably to organism fitness in
      naturally evolving populations.

PMID- 18832442
TI  - Unraveling ancient hexaploidy through multiply-aligned angiosperm gene maps.
AB  - Large-scale (segmental or whole) genome duplication has been recurring in
      angiosperm evolution. Subsequent gene loss and rearrangements further affect gene
      copy numbers and fractionate ancestral gene linkages across multiple chromosomes.
      The fragmented "multiple-to-multiple" correspondences resulting from this
      distinguishing feature of angiosperm evolution complicates comparative genomic
      studies. Using a robust computational framework that combines information from
      multiple orthologous and duplicated regions to construct local syntenic networks,
      we show that a shared ancient hexaploidy event (or perhaps two roughly concurrent
      genome fusions) can be inferred based on the sequences from several divergent
      plant genomes. This "paleo-hexaploidy" clearly preceded the rosid-asterid split,
      but it remains equivocal whether it also affected monocots. The model resulting
      from our multi-alignments lays the foundation for approximating the number and
      arrangement of genes in the last universal common ancestor of angiosperms.
      Comparative analysis of inferred homologous genes derived from this model shows
      patterns of preferential gene retention or loss after polyploidy and reveals
      large variability of nucleotide substitution rates among plant nuclear genomes.

PMID- 18832444
TI  - Familial non-medullary thyroid carcinoma displays the features of clinical
      anticipation suggestive of a distinct biological entity.
AB  - Non-medullary thyroid carcinoma (NMTC) is mostly sporadic, but familial
      clustering is described. We aimed to compare the features of patients with
      sporadic and familial NMTC (FNMTC) patients and to assess whether FNMTC patients
      with parent-child relationship exhibit the 'anticipation' phenomenon (earlier age
      at disease onset and increased severity in successive generations). Among 300
      NMTCs followed in the Section of Endocrinology (University of Siena, Italy), 34
      (11.3%) patients, all with the papillary histotype, (16 kindred), met the
      criteria of FNMTC. Twenty-seven of them (79.4%) exhibited a parent-child
      relationship and seven (20.6%) a sibling relationship. These patients were
      compared with 235 patients with sporadic papillary thyroid cancer (PTCs). To
      analyze the features of FNMTC of the first and second generations, we cumulated
      the series of Siena with 32 additional FNMTC patients (15 kindred) from the
      Department of Endocrinology-Endocrine Oncology, Thessaloniki, Greece. Significant
      difference between sporadic PTC and FNMTC patients included more frequent tumor
      multifocality (P=0.001) and worse final outcome in FNMTC patients (P=0.001).
      Among 47 FNMTC with parent-child relationship, we found an earlier age at disease
      presentation (P<0.0001), diagnosis (P<0.0001), and disease onset (P=0.04) in the
      second generation when compared with the first generation. Patients in the second
      generation were more frequently males (P=0.02); their tumors were more frequently
      multifocal (P=0.003) and bilateral (P=0.01), had higher rate of lymph node
      metastases at surgery (P=0.02) and worse outcome (P=0.04) when compared with the
      first generation. In conclusion, FNMTC displays the features of clinical
      'anticipation' with the second generation acquiring the disease at an earlier age
      and having more advanced disease at presentation.

PMID- 18832443
TI  - Finding friends and enemies in an enemies-only network: a graph diffusion kernel
      for predicting novel genetic interactions and co-complex membership from yeast
      genetic interactions.
AB  - The yeast synthetic lethal genetic interaction network contains rich information
      about underlying pathways and protein complexes as well as new genetic
      interactions yet to be discovered. We have developed a graph diffusion kernel as
      a unified framework for inferring complex/pathway membership analogous to
      "friends" and genetic interactions analogous to "enemies" from the genetic
      interaction network. When applied to the Saccharomyces cerevisiae synthetic
      lethal genetic interaction network, we can achieve a precision around 50% with
      20% to 50% recall in the genome-wide prediction of new genetic interactions,
      supported by experimental validation. The kernels show significant improvement
      over previous best methods for predicting genetic interactions and protein co
      complex membership from genetic interaction data.

PMID- 18832445
TI  - The endocannabinoid anandamide inhibits cholangiocarcinoma growth via activation
      of the noncanonical Wnt signaling pathway.
AB  - Cholangiocarcinomas are cancers that have poor prognosis and limited treatment
      options. The noncanonical Wnt pathway is mediated predominantly by Wnt 5a, which
      activates a Ca(2+)-dependent pathway involving protein kinase C, or a Ca(2+)
      independent pathway involving the orphan receptor Ror2 and subsequent activation
      of Jun NH(2)-terminal kinase (JNK). This pathway is associated with growth
      suppressing effects in numerous cell types. We have shown that anandamide
      decreases cholangiocarcinoma growth in vitro. Therefore, we determined the
      effects of anandamide on cholangiocarcinoma tumor growth in vivo using a
      xenograft model and evaluated the effects of anandamide on the noncanonical Wnt
      signaling pathways. Chronic administration of anandamide decreased tumor growth
      and was associated with increased Wnt 5a expression in vitro and in vivo.
      Treatment of cholangiocarcinoma cells with recombinant Wnt 5a decreased cell
      proliferation in vitro. Neither anandamide nor Wnt 5a affected intracellular
      calcium release, but both increased the JNK phosphorylation. Stable knockdown of
      Wnt 5a or Ror2 expression in cholangiocarcinoma cells abolished the effects of
      anandamide on cell proliferation and JNK activation. Modulation of the
      endocannabinoid system may be important in cholangiocarcinoma treatment. The
      antiproliferative actions of the noncanonical Wnt signaling pathway warrants
      further investigation to dissect the mechanism by which this may occur.

PMID- 18832446
TI  - Estrogen prevents intestinal inflammation after trauma-hemorrhage via
      downregulation of angiotensin II and angiotensin II subtype I receptor.
AB  - Although angiotensin II (Ang II) plays a key role in development of organ
      ischemia-reperfusion injury, it remains unclear whether it is involved in
      development of intestinal injury following trauma-hemorrhage (T-H). Studies have
      shown that 17beta-estradiol (E2) administration following T-H improves small
      intestinal blood flow; however, it is unclear whether Ang II plays a role in this
      E2-mediated salutary effect. Male Sprague-Dawley rats underwent laparotomy and
      hemorrhagic shock (removal of 60% total blood volume, fluid resuscitation after
      90 min). At onset of resuscitation, rats were treated with vehicle, E2, or E2 and
      estrogen receptor antagonist ICI 182,780 (ICI). A separate group of rats was
      treated with Ang II subtype I receptor (AT1R) antagonist losartan. At 24 h after
      T-H, plasma Ang II, IL-6, TNF-alpha, intercellular adhesion molecule (ICAM)-1,
      cytokine-induced neutrophil chemoattractant (CINC)-1 and CINC-3 levels,
      myeloperoxidase (MPO) activity, and AT1R expression were determined. T-H
      significantly increased plasma and intestinal Ang II, IL-6, TNF-alpha levels,
      intestinal ICAM-1, CINC-1, CINC-3 levels, MPO activity, and AT1R protein compared
      with shams. E2 treatment following T-H attenuated increased intestinal MPO
      activity, Ang II level, and AT1R protein expression. ICI administration abolished
      the salutary effects of E2. In contrast, losartan administration attenuated
      increased MPO activity without affecting Ang II and AT1R levels. Thus Ang II
      plays a role in producing small intestine inflammation following T-H, and the
      salutary effects of E2 on intestinal inflammation are mediated in part by Ang II
      and AT1R downregulation.

PMID- 18832447
TI  - Immune-mediated signaling in intestinal goblet cells via PI3-kinase- and AKT
      dependent pathways.
AB  - In the intestinal epithelium, activation of phosphatidylinositol 3-kinase (PI3
      kinase)/AKT pathways, via growth factor-mediated signaling, has been shown to
      regulate cell proliferation and inhibit apoptosis. An immune-activated receptor
      critical for Th2 immune responses, IL-4Ralpha can also activate PI3-kinase via
      insulin receptor substrate (IRS)-dependent signaling. Here, using the intestinal
      goblet cell-specific gene RELMbeta, we investigated the effect of PI3-kinase
      activation via Th2 immune responses on the goblet cell phenotype. IL-13
      stimulation activated PI3-kinase and AKT signal transduction in LS174T cells. Not
      only did pharmacological inhibition of PI3-kinase and AKT1/2 inhibit RELMbeta
      induction by IL-13, but AKT inhibition also significantly reduced constitutive
      basal expression of RELMbeta, a response reproduced by the simultaneous
      pharmacological inhibition of both epidermal growth factor receptor and IGF-I
      receptor signaling. In vivo, the disruption of phosphatase and tensin homolog
      deleted on chromosome 10 (PTEN), an inhibitor of PI3-kinase activation, led to
      the activation of RELMbeta expression in the small intestine. Furthermore,
      induction of an intestinal Th2 immune response by infection with a small
      intestinal nematode parasite, Heligmosomoides polygyrus, led to enhanced
      epithelial cell proliferation, activation of AKT as demonstrated by the loss of
      Foxo1 nuclear localization, and robust induction of RELMbeta expression in wild
      type, but not IL-4Ralpha knockout, mice. These results demonstrate that Th2
      immune responses can regulate goblet cell responses by activation of PI3-kinase
      and AKT pathways via IL-4Ralpha.

PMID- 18832448
TI  - Effect of ethanol on hydrogen peroxide-induced AMPK phosphorylation.
AB  - AMP-activated protein kinase (AMPK) responds to oxidative stress. Previous work
      has shown that ethanol treatment of cultured hepatoma cells and of mice inhibited
      the activity of AMPK and reduced the amount of AMPK protein. Ethanol generates
      oxidative stress in the liver. Since AMPK is activated by reactive oxygen
      species, it seems paradoxical that ethanol would inhibit AMPK in the hepatoma
      cells. In an attempt to understand the mechanism whereby ethanol inhibits AMPK,
      we studied the effect of ethanol on AMPK activation by exogenous hydrogen
      peroxide. The effects of ethanol, hydrogen peroxide, and inhibitors of protein
      phosphatase 2A (PP2A) [either okadaic acid or PP2A small interference RNA
      (siRNA)] on AMPK phosphorylation and activity were examined in rat hepatoma cells
      (H4IIEC3) and HeLa cells. In H4IIEC3 cells, hydrogen peroxide (H(2)O(2), 1 mM)
      transiently increased the level of phospho-AMPK to 1.5-fold over control (P <
      0.05). Similar findings were observed in HeLa cells, which do not express the
      upstream AMPK kinase, LKB1. H(2)O(2) markedly increased the phosphorylation of
      LKB1 in H4IIEC3 cells. Ethanol significantly inhibited the phosphorylation of PKC
      zeta, LKB1, and AMPK caused by exposure to H(2)O(2). This inhibitory effect of
      ethanol required its metabolism. More importantly, the inhibitory effects of
      ethanol on H(2)O(2)-induced AMPK phosphorylation were attenuated by the presence
      of the PP2A inhibitor, okadaic acid, or PP2A siRNA. The inhibitory effect of
      ethanol on AMPK phosphorylation is exerted through the inhibition of PKC-zeta and
      LKB1 phosphorylation and the activation of PP2A.

PMID- 18832449
TI  - Calcium/calmodulin-dependent phosphorylation of tumor protein D52 on serine
      residue 136 may be mediated by CAMK2delta6.
AB  - Tumor protein D52 is expressed at relatively high levels in cells within the
      gastrointestinal tract that undergo classical exocytosis and is overexpressed in
      several cancers. Current evidence supports a role for D52 in the regulation of
      vesicular trafficking. D52 function(s) are regulated by calcium-dependent
      phosphorylation; however, the intracellular mechanisms that mediate this process
      are not well characterized. The goal of this study was to identify the calcium
      dependent phosphorylation site(s) in D52 and to characterize the protein
      kinase(s) that mediate this phosphorylation. Using mass spectrometry and site
      directed mutagenesis, we identified a single amino acid residue, S(136), that
      undergoes increased phosphorylation upon elevation of intracellular Ca(2+)
      concentration. A phosphospecific antibody (pS(136)) was produced and used to
      characterize D52 kinase activity in gastric mucosal, colonic T84, and HEK293
      cells. By using D52 as a substrate, a protein kinase with a molecular weight
      (M(r)) of approximately 50 kDa was identified with "in gel" assays. This kinase
      comigrated with rat brain calcium/calmodulin-dependent protein kinase
      (CAMK2)alpha cross-reacted with pan-specific CAMK2 antibodies as well as with
      anti-active CAMK2 (pT(286/287)) antibody when activated. Carbachol-stimulated
      phosphorylation of S(136) was inhibited by the CAMK2 inhibitor KN93 (IC(50) 38
      microM) and by the calmodulin antagonist W7 (IC(50) 3.3 nM). A previously
      uncharacterized CAMK2 isoform, CAMK2delta6, which has the same domain structure
      and M(r) as CAM2alpha, was identified in gastric mucosa by RT-PCR. The cloned,
      expressed protein comigrated with D52 kinase and colocalized with D52 protein in
      T84 and HEK293 cells. These findings support a role for CAMK2delta6 in the
      mediation of D52 phosphorylation.

PMID- 18832450
TI  - Endothelin-3 stimulates survival of goblet cells in organotypic cultures of fetal
      human colonic epithelium.
AB  - Cells within the normal human colonic epithelium undergo a dynamic cycle of
      growth, differentiation, and death. The organotypic culture system of human fetal
      colonic epithelial cells seeded on top of collagen gels with embedded colonic
      fibroblasts allowed prolonged culture of the colonic epithelial cells (Kalabis J,
      Patterson MJ, Enders GM, Marian B, Iozzo RV, Rogler G, Gimotty PA, Herlyn M.
      FASEB J 17: 1115-1117, 2003). Herein, we have evaluated the role of endothelin-3
      (ET3) and both cognate endothelin receptors (ETRA, ETRB) for human colonic
      epithelial cell growth and survival. ET3 was produced continuously by the
      fibroblasts as a result of adenovirus-mediated gene transfer. The presence and
      function of the endothelin receptors (ETRs) in epithelial cells was evaluated by
      [(3)H]thymidine incorporation using primary epithelial cells in monoculture and
      by immunohistochemistry on human fetal and adult paraffin-embedded tissues. In
      organotypic culture, ET3 increased the number of goblet cells but not of
      enteroendocrine cells. The increase in goblet cells was caused by prolonged cell
      survival and differentiation. The inhibition of both ETRA and ETRB significantly
      decreased the number of goblet cells and proliferation in epithelial cells,
      whereas the number of enteroendocrine cells remained unchanged. ET3 induced
      activation of IkappaB and MAPK in the epithelial cells, suggesting that these
      signaling pathways mediate its proproliferation and prosurvival activities. Our
      results demonstrate that ET3 is involved in regulating human colonic epithelial
      cell proliferation and survival, particularly for goblet cells, and may be an
      important component of colonic homeostasis.

PMID- 18832451
TI  - Regulatory mechanisms underlying agmatine homeostasis in humans.
AB  - Regulation of agmatine homeostasis has so far only been poorly defined. In the
      present study, three mechanisms regulating human agmatine homeostasis were
      investigated. 1) Enzymatic regulation: expression of arginine decarboxylase,
      diamine oxidase, and ornithine decarboxylase in human colon neoplastic tissue
      was, at the mRNA level, about 75% and 50% lower and 150% higher, respectively,
      than in the adjacent normal tissue; expression of agmatinase was unchanged. 2)
      Bacteria-derived agmatine: ten representative bacteria strains of the human
      intestinal microbiota considerably differed in agmatine production and its efflux
      into their surrounding fluid, suggesting that the composition of the intestinal
      microbiota influences the agmatine availability in the gut lumen for absorption.
      3) Regulation of blood plasma agmatine concentration by the human liver: at low
      concentrations in portal venous blood plasma, agmatine either slightly increased
      or further decreased in blood plasma through liver passage. Above a threshold of
      14 ng/ml agmatine in the portal venous blood plasma, substantial hepatic agmatine
      removal from blood occurred. Taken together, a perturbation of agmatine
      homeostasis has been proven to be involved in the regulation of malignant cell
      proliferation. The amount of agmatine available for absorption, which is an
      important physiological source of agmatine in the human organism, should differ
      considerably depending on the composition of the bacterial flora in the chyme
      since the various species of intestinal bacteria largely differ in their ability
      to form agmatine. Finally, evidence has been presented that the liver plays a
      crucial physiological role in the maintenance of agmatine homeostasis in the
      human organism.

PMID- 18832452
TI  - Probiotics enhance pancreatic glutathione biosynthesis and reduce oxidative
      stress in experimental acute pancreatitis.
AB  - Factors determining severity of acute pancreatitis (AP) are poorly understood.
      Oxidative stress causes acinar cell injury and contributes to the severity,
      whereas prophylactic probiotics ameliorate experimental pancreatitis. Our
      objective was to study how probiotics affect oxidative stress, inflammation, and
      acinar cell injury during the early phase of AP. Fifty-three male Sprague-Dawley
      rats were randomly allocated into groups: 1) control, 2) sham procedure, 3) AP
      with no treatment, 4) AP with probiotics, and 5) AP with placebo. AP was induced
      under general anesthesia by intraductal glycodeoxycholate infusion (15 mM) and
      intravenous cerulein (5 microg.kg(-1).h(-1), for 6 h). Daily probiotics or
      placebo were administered intragastrically, starting 5 days prior to AP. After
      cerulein infusion, pancreas samples were collected for analysis including lipid
      peroxidation, glutathione, glutamate-cysteine-ligase activity, histological
      grading of pancreatic injury, and NF-kappaB activation. The severity of
      pancreatic injury correlated to oxidative damage (r = 0.9) and was ameliorated by
      probiotics (1.5 vs. placebo 5.5; P = 0.014). AP-induced NF-kappaB activation was
      reduced by probiotics (0.20 vs. placebo 0.53 OD(450nm)/mg nuclear protein; P <
      0.001). Probiotics attenuated AP-induced lipid peroxidation (0.25 vs. placebo
      0.51 pmol malondialdehyde/mg protein; P < 0.001). Not only was AP-induced
      glutathione depletion prevented (8.81 vs. placebo 4.1 micromol/mg protein, P <
      0.001), probiotic pretreatment even increased glutathione compared with sham rats
      (8.81 vs. sham 6.18 miccromol/mg protein, P < 0.001). Biosynthesis of glutathione
      (glutamate-cysteine-ligase activity) was enhanced in probiotic-pretreated
      animals. Probiotics enhanced the biosynthesis of glutathione, which may have
      reduced activation of inflammation and acinar cell injury and ameliorated
      experimental AP, via a reduction in oxidative stress.

PMID- 18832453
TI  - Glycosaminoglycan origin and structure revealed by multivariate analysis of NMR
      and CD spectra.
AB  - Principal component analysis (PCA) is a method of simplifying complex datasets to
      generate a lower number of parameters, while retaining the essential differences
      and allowing objective comparison of large numbers of datasets.
      Glycosaminoglycans (GAGs) are a class of linear sulfated carbohydrates with
      diverse sequences and consequent complex conformation and structure. Here, PCA is
      applied to three problems in GAG research: (i) distinguishing origins of heparin
      preparations, (ii) structural analysis of heparin derivatives, and (iii)
      classification of chondroitin sulfates (CS). The results revealed the following.
      (i) PCA of heparin (13)C NMR spectra allowed their origins to be distinguished
      and structural differences were identified. (ii) Analysis of the information-rich
      (1)H and (13)C NMR spectra of a series of systematically modified heparin
      derivatives uncovered underlying properties. These included the presence of
      interactions between residues, providing evidence that a degree of degeneracy
      exists in linkage geometry and that a different degree of variability exists for
      the two types of glycosidic linkage. The relative sensitivity of each position (C
      or H nucleus) in the disaccharide repeating unit to changes in O-, N-sulfation
      and N-acetylation was also revealed. (iii) Analysis of the (1)H NMR and CD
      spectra of a series of CS samples from different origins allowed their structural
      classification and highlighted the power of employing complementary spectroscopic
      methods in concert with PCA.

PMID- 18832454
TI  - Chemical and in situ characterization of macromolecular components of the cell
      walls from the green seaweed Codium fragile.
AB  - A comprehensive analysis of the carbohydrate-containing macromolecules from the
      coencocytic green seaweed Codium fragile and their arrangement in the cell wall
      was carried out. Cell walls in this seaweed are highly complex structures
      composed of 31% (w/w) of linear (1-->4)-beta-D-mannans, 9% (w/w) of pyruvylated
      arabinogalactan sulfates (pAGS), and low amounts of hydroxyproline rich
      glycoprotein epitopes (HRGP). In situ chemical imaging by synchrotron radiation
      Fourier transform infrared (SR-FTIR) microspectroscopy and by immunolabeling
      using antibodies against specific cell wall carbohydrate epitopes revealed that
      beta-d-mannans and pAGS are placed in the middle part of the cell wall, whereas
      HRGP epitopes (arabinogalactan proteins (AGPs) and extensins) are located on the
      wall boundaries, especially in the utricle apical zone. pAGS are sulfated at C-2
      and/or C-4 of the 3-linked beta-L-arabinopyranose units and at C-4 and/or C-6 of
      the 3-linked beta-D-galactopyranose residues. In addition, high levels of ketals
      of pyruvic acid were found mainly at 3,4- of some terminal beta-D-Galp units
      forming a five-membered ring. Ramification was found at some C-6 of the 3-linked
      beta-D-Galp units. In agreement with the immunolabeled AGP epitopes, a
      nonsulfated branched furanosidic arabinan with 5-linked alpha-L-Araf, 3,5-linked
      alpha-L-Araf, and terminal alpha-L-Araf units and a nonsulfated galactan
      structure composed of 3-(3,6)-linked beta-D-Galp residues, both typical of type
      II AG glycans were found, suggesting that AGP structures are present at low
      levels in the cell walls of this seaweed. Based on this study, it is starting to
      emerge that Codium has developed unique cell wall architecture, when compared,
      not only with that of vascular plants, but also with other related green seaweeds
      and algae.

PMID- 18832455
TI  - Methylation-specific multiplex ligation-dependent probe amplification enables a
      rapid and reliable distinction between male FMR1 premutation and full-mutation
      alleles.
AB  - Fragile X syndrome is the most common cause of inherited mental retardation and
      the second most common cause of mental impairment after trisomy 21. It occurs
      because of a failure to express the fragile X mental retardation protein. The
      most common molecular basis for the disease is the abnormal expansion of the
      number of CGG repeats in the fragile X mental retardation 1 gene (FMR1). Based on
      the number of repeats, it is possible to distinguish four types of alleles:
      normal (5 to 44 repeats), intermediate (45 to 54), premutation (55 to 200), and
      full mutation (>200). Today, the diagnosis of fragile X syndrome is performed
      through a combination of PCR to identify fewer than 100 repeats and of Southern
      blot analysis to identify longer alleles and the methylation status of the FMR1
      promoter. We have developed a methylation-specific multiplex ligation-dependent
      probe amplification assay to analyze male fragile X syndrome cases with long
      repeat tracts that are not amplifiable by PCR. This inexpensive, rapid and robust
      technique provides not only a clear distinction between male pre- and full
      mutation FMR1 alleles, but also permits the identification of genomic deletions,
      a less frequent cause of fragile X syndrome.

PMID- 18832456
TI  - Delineation of HER2 gene status in breast carcinoma by silver in situ
      hybridization is reproducible among laboratories and pathologists.
AB  - An automated enzyme metallographic silver in situ hybridization method (SISH) has
      been reported to successfully determine human epidermal growth factor receptor 2
      (HER2) gene amplification. We evaluated the staining and interpretative
      reproducibility of the HER2 SISH assay at five laboratories and compared SISH
      results with other in situ hybridization (ISH) methods. The HER2 gene status of
      89 breast carcinomas was analyzed in parallel using manual dual-color
      fluorescence ISH, manual chromogenic ISH, and bright-field automated SISH. A
      total of 1098 SISH-stained slides were evaluated. For comparison, all specimens
      were stained by 4B5 immunohistochemistry for HER2 protein expression.
      Interpretation was performed by pathologists at five different laboratories using
      the algorithms provided by the manufacturers and the guidelines of American
      Society of Clinical Oncology/College of American Pathologists. Staining and
      interpretative reproducibility were measured through the computation of weighted
      kappa statistics. Following the optimization of SISH staining, 1077/1098 (98%) of
      slides were evaluable. Excellent reproducibility and efficacy of HER2 SISH
      staining, and interobserver interpretation (Kw = 0.91), were observed among five
      sites. For the 89 invasive breast cancer cases, the overall rate of concordance
      between consensus 4B5 and consensus SISH, fluorescence ISH, and chromogenic ISH
      was 96.6% (86/89), 97.8% (87/89), and 96.6% (86/89), respectively. Overall
      concordance between positive and negative SISH and fluorescence ISH results, as
      well as between individual and consensus positive and negative SISH results, was
      excellent (P < 0.001).

PMID- 18832457
TI  - An array-based analysis of microRNA expression comparing matched frozen and
      formalin-fixed paraffin-embedded human tissue samples.
AB  - MicroRNAs (miRNAs) are small, noncoding RNAs that suppress gene expression at the
      posttranscriptional level via an antisense RNA-RNA interaction. miRNAs used for
      array-based profiling are generally purified from either snap-frozen or fresh
      samples. Because tissues found in most pathology departments are available only
      in formalin-fixed and paraffin-embedded (FFPE) states, we sought to evaluate
      miRNA derived from FFPE samples for microarray analysis. In this study, miRNAs
      extracted from matched snap-frozen and FFPE samples were profiled using the
      Agilent miRNA array platform (Agilent, Santa Clara, CA). Each miRNA sample was
      hybridized to arrays containing probes interrogating 470 human miRNAs. Seven
      cases were compared in either duplicate or triplicate. Intrachip and interchip
      analyses demonstrated that the processes of miRNA extraction, labeling, and
      hybridization from both frozen and FFPE samples are highly reproducible and add
      little variation to the results; technical replicates showed high correlations
      with one another (Kendall tau, 0.722 to 0.853; Spearman rank correlation
      coefficient, 0.891 to 0.954). Our results showed consistent high correlations
      between matched frozen and FFPE samples (Kendall tau, 0.669 to 0.815; Spearman
      rank correlation coefficient, 0.847 to 0.948), supporting the use of FFPE-derived
      miRNAs for array-based, gene expression profiling.

PMID- 18832458
TI  - KRAS mutations: an old oncogene becomes a new predictive biomarker.
AB  - This commentary highlights a novel assay for detection of mutations in KRAS,
      which have recently emerged as a useful negative predictive biomarker.

PMID- 18832459
TI  - Amplification-based DNA analysis in the diagnosis of prosthetic joint infection.
AB  - Microbiological cultures are moderately sensitive for diagnosing prosthetic joint
      infection (PJI). This study was conducted to determine whether amplification
      based DNA methods applied on intraoperative samples could enhance PJI diagnosis
      compared with culture alone in routine surgical practice. Revision arthroplasty
      was performed for suspected PJI (n = 41) and osteoarthrosis control (n = 28)
      patients, and a diagnosis of PJI was confirmed in 34 patients. Amplification by
      polymerase chain reaction was performed on both 16S ribosomal DNA universal
      target genes and femA Staphylococcus-specific target genes. Species
      identification was achieved through amplicon sequencing. Amplification of the
      femA gene led to subsequent testing for methicillin resistance by amplification
      of the mecA gene. Microbiological and molecular assays identified a causative
      organism in 22 of 34 patients (64.7%) and in 31 of 34 patients (91.2%),
      respectively. In 18 of the 22 culture-positive patients, molecular and
      microbiological results were concordant for bacterial genus, species, and/or
      methicillin resistance. Bacterial agents were identified only by molecular
      methods in nine PJI patients, including seven who were receiving antibiotics at
      the time of surgery and one with recent but not concomitant antibiotherapy. DNA
      based methods were found to effectively complement microbiological methods,
      without interfering with existing procedures for sample collection, for the
      identification of causative pathogens from intraoperative PJI samples, especially
      in patients with recent or concomitant antibiotherapy.

PMID- 18832460
TI  - WGA allows the molecular characterization of a novel large CFTR rearrangement in
      a black South African cystic fibrosis patient.
AB  - By performing extensive scanning of whole coding and flanking sequences of the
      cystic fibrosis (CF) transmembrane conductance regulator (CFTR) gene, we had
      previously identified the CF-causing mutations in black South African patients of
      different ethnic groups suspected with the disease. Of ten samples analyzed,
      there were six remaining that had either one (n = 2) or two (n = 4) unidentified
      CFTR alleles that have now been tested for large rearrangements using a
      semiquantitative fluorescent PCR assay. A novel deletion encompassing CFTR exon 2
      was detected in one patient who was heterozygous for the mutation 3120+1G>A. The
      Caucasian deletion involving the same exon [c.54-5811_c.164+2186del8108ins182]
      was ruled out. The DNA had been stored for more than 12 years and only minute
      quantities remained. We thus used a whole-genome amplification method based on
      multiple displacement amplification to generate sufficient amounts of DNA to
      characterize the intronic breakpoints and identify the deletion at the genomic
      level. Mapping and sequencing the breakpoint junctions revealed a novel large
      deletion [c.54-1161_c.164+1603del2875]. We have designed a simple test to
      specifically detect the presence or absence of this large rearrangement. This
      study reports the first large CFTR rearrangement in a black South African CF
      patient, further defining the molecular spectrum of CF that will be useful for
      improving genetic testing and counseling in this region.

PMID- 18832461
TI  - Rapid screening assay for KRAS mutations by the modified smart amplification
      process.
AB  - Previously, the smart amplification process version 2 (SMAP-2) was developed to
      detect mutations from tissue and in crude cell lysates and has been used for
      rapid diagnosis of specific somatic mutations with single-nucleotide precision.
      The purpose of this study was to develop a rapid and practical method to detect
      cancer and metastasis in specimens using the SMAP-2 assay. We developed modified
      SMAP-2 assays that enabled detection of any change in a single codon using a
      single assay. Rapid SMAP-2 screening assays are suitable for routine clinical
      identification of critical amino acid substitutions such as codon 12 mutations in
      KRAS. Primers bracketing the first two nucleotides of KRAS codon 12 were designed
      so that all possible alleles would be amplified by the SMAP-2 assay. In
      combination with the peptide nucleic acid (PNA) with exact homology to the wild
      type allele, our assay amplified all mutant alleles except for the wild-type
      sequence. With this new assay design (termed PNA-clamp SMAP-2), we could detect
      KRAS mutations within 60 minutes, including sample preparation. We compared
      results from PNA-clamp SMAP-2 assay, polymerase chain reaction-restriction
      fragment length polymorphism, and direct sequencing of clinical samples from
      pancreatic cancer patients and demonstrated perfect concordance. The PNA-clamp
      SMAP-2 method is a rapid, simple, and highly sensitive detection assay for cancer
      mutations.

PMID- 18832462
TI  - Keeping up with the next generation: massively parallel sequencing in clinical
      diagnostics.
AB  - The speed, accuracy, efficiency, and cost-effectiveness of DNA sequencing have
      been improving continuously since the initial derivation of the technique in the
      mid-1970s. With the advent of massively parallel sequencing technologies, DNA
      sequencing costs have been dramatically reduced. No longer is it unthinkable to
      sequence hundreds or even thousands of genes in a single individual with a
      suspected genetic disease or complex disease predisposition. Along with the
      benefits offered by these technologies come a number of challenges that must be
      addressed before wide-scale sequencing becomes accepted medical practice.
      Molecular diagnosticians will need to become comfortable with, and gain
      confidence in, these new platforms, which are based on radically different
      technologies compared to the standard DNA sequencers in routine use today.
      Experience will determine whether these instruments are best applied to
      sequencing versus resequencing. Perhaps most importantly, along with increasing
      read lengths inevitably comes increased ascertainment of novel sequence variants
      of uncertain clinical significance, the postanalytical aspects of which could bog
      down the entire field. But despite these obstacles, and as a direct result of the
      promises these sequencing advances present, it will likely not be long before
      next-generation sequencing begins to make an impact in molecular medicine. In
      this review, technical issues are discussed, in addition to the practical
      considerations that will need to be addressed as advances push toward personal
      genome sequencing.

PMID- 18832463
TI  - Rapid allelic discrimination by TaqMan PCR for the detection of the Gilbert's
      syndrome marker UGT1A1*28.
AB  - Gilbert's syndrome causes mild, unconjugated hyperbilirubinemia and is present in
      approximately 10% of the Caucasian population. The basis of the disorder is a 70%
      reduction in bilirubin glucuronidation catalyzed by the UDP
      glucuronosyltransferase 1A1 (UGT1A1), which, in Caucasians, is the result of a
      homozygous TA insertion into the promoter region of the UGT1A1 gene (UGT1A1*28).
      Homozygous carriers of UGT1A1*28 as well as those with additional UGT1A variants
      can suffer from severe irinotecan toxicity or jaundice during treatment with the
      protease inhibitor atazanavir. UGT1A1*28 genotyping identifies patients at risk
      for drug toxicity and can increase drug safety by dose individualization. Rapid
      and facile UGT1A1*28 genotyping is therefore of great clinical importance. Two
      hundred ninety-one patients with suspected Gilbert's syndrome were genotyped
      using the TaqMan 5'nuclease assay with minor groove binder-non fluorescent quench
      probes; results were confirmed by direct sequencing. Ninety-six patients (33%)
      were homozygous for UGT1A1*28, which was verified by direct sequencing of a
      different PCR product showing 100% concordance with the TaqMan PCR results. We
      describe a novel UGT1A1*28 genotyping method that employs allelic discrimination
      by TaqMan PCR. This assay provides a rapid, high-throughput, and cost-effective
      method for Gilbert's syndrome genotyping, which is of value for pretreatment
      screening of potential irinotecan toxicity. The method utilizes a technological
      platform that is widely used in clinical practice and could therefore be easily
      adapted for routine clinical applications.

PMID- 18832464
TI  - The frequency of immunoglobulin heavy chain gene and T-cell receptor gamma-chain
      gene rearrangements and Epstein-Barr virus in ALK+ and ALK- anaplastic large cell
      lymphoma and other peripheral T-cell lymphomas.
AB  - We previously identified a relatively high frequency of B-cell proliferations
      along with simultaneous T-cell receptor gamma-chain gene (TRG) and immunoglobulin
      heavy chain gene (IGH) rearrangements in a series of angioimmunoblastic T-cell
      lymphoma and peripheral T-cell lymphoma, unspecified. Here, we report on a series
      of 74 peripheral T-cell lymphoma (PTCL) cases composed entirely of specific PTCL
      subtypes, including 28 cases of ALK+ anaplastic large-cell lymphoma (ALCL), 35
      cases of ALK- ALCL, and 11 cases that represent other specific PTCL subtypes. We
      performed IGH and TRG gene rearrangement studies and in situ hybridization for
      Epstein-Barr virus (EBV) to determine the frequency of IGH clonality and to
      investigate the relationship between EBV, clonality, and associated B-cell
      proliferations. Using BIOMED-2 PCR assays, we detected TRG clones in 64 of 74
      (86%) cases and IGH clones in 6 of 74 (8%) cases, with all IGH-positive cases
      exhibiting a concurrent TRG clone. Despite the detection of occasional IGH
      clones, there was no correlation between IGH clonality and EBV, and B-cell
      proliferations were not identified in any of the cases. These findings suggest
      that other factors contribute to IGH clonality and demonstrate that, in the
      absence of an associated B-cell proliferation, IGH clonality occurs infrequently
      (8%) in specific PTCL subtypes.

PMID- 18832465
TI  - Parkinsonism and impaired axonal transport in a mouse model of frontotemporal
      dementia.
AB  - Frontotemporal dementia (FTD) is characterized by cognitive and behavioral
      changes and, in a significant subset of patients, Parkinsonism.
      Histopathologically, FTD frequently presents with tau-containing lesions, which
      in familial cases result from mutations in the MAPT gene encoding tau. Here we
      present a novel transgenic mouse strain (K3) that expresses human tau carrying
      the FTD mutation K369I. K3 mice develop a progressive histopathology that is
      reminiscent of that in human FTD with the K369I mutation. In addition, K3 mice
      show early-onset memory impairment and amyotrophy in the absence of overt
      neurodegeneration. Different from our previously generated tau transgenic
      strains, the K3 mice express the transgene in the substantia nigra (SN) and show
      an early-onset motor phenotype that reproduces Parkinsonism with tremor,
      bradykinesia, abnormal gait, and postural instability. Interestingly, motor
      performance of young, but not old, K3 mice improves upon L-dopa treatment, which
      bears similarities to Parkinsonism in FTD. The early-onset symptoms in the K3
      mice are mechanistically related to selectively impaired anterograde axonal
      transport of distinct cargos, which precedes the loss of dopaminergic SN neurons
      that occurs in aged mice. The impaired axonal transport in SN neurons affects,
      among others, vesicles containing the dopamine-synthesizing enzyme tyrosine
      hydroxylase. Distinct modes of transport are also impaired in sciatic nerves,
      which may explain amyotrophy. Together, the K3 mice are a unique model of FTD
      associated Parkinsonism, with pathomechanistic implications for the human
      pathologic process.

PMID- 18832466
TI  - Transient and selective overexpression of D2 receptors in the striatum causes
      persistent deficits in conditional associative learning.
AB  - Cognitive deficits in schizophrenia are thought to derive from a hypofunction of
      the prefrontal cortex (PFC), but the origin of the hypofunction is unclear. To
      explore the nature of this deficit, we genetically modified mice to model the
      increase in striatal dopamine D(2) receptors (D(2)Rs) observed in patients with
      schizophrenia. Previously, we reported deficits in spatial working memory tasks
      in these mice, congruent with the working memory deficits observed in
      schizophrenia. However, patients with schizophrenia suffer from deficits in many
      executive functions, including associative learning, planning, problem solving,
      and nonspatial working memory. We therefore developed operant tasks to assay two
      executive functions, conditional associative learning (CAL) and nonspatial
      working memory. Striatal D(2)R-overexpressing mice show a deficit in CAL because
      of perseverative behavior, caused by interference from the previous trial. D(2)R
      up-regulation during development was sufficient to cause this deficit, because
      switching off the transgene in adulthood did not rescue the phenotype. We
      validated prefrontal dependency of CAL by using neurotoxic lesions. Lesions of
      the medial PFC including the anterior cingulate, infralimbic, and prelimbic
      cortices impair CAL because of increased interference from previously rewarded
      trials, exactly as observed in D(2)R transgenic mice. In contrast, lesions
      restricted to the infralimbic and prelimbic cortices have no effect on CAL but
      impair performance in the nonspatial working memory task. These assays not only
      give us insight into how excess striatal D(2)Rs affect cognition but also provide
      tools for studying cognitive endophenotypes in mice.

PMID- 18832467
TI  - mda-9/Syntenin promotes metastasis in human melanoma cells by activating c-Src.
AB  - The scaffold PDZ-domain containing protein mda-9/syntenin functions as a positive
      regulator of cancer cell progression in human melanoma and other tumors. mda
      9/Syntenin regulates cell motility and invasion by altering defined biochemical
      and signaling pathways, including focal adhesion kinase (FAK), p38 mitogen
      activated protein kinase (MAPK) and NF-kappaB, but precisely how mda-9/syntenin
      organizes these multiprotein signaling complexes is not well understood. Using a
      clinically relevant human melanoma model, we demonstrate that mda-9/syntenin
      physically interacts with c-Src and this communication correlates with an
      increase in FAK/c-Src complex formation and c-Src activation. Inhibiting mda
      9/syntenin, using an adenovirus expressing antisense mda-9/syntenin or addition
      of c-Src siRNA, suppresses melanoma cell migration, anchorage-independent growth,
      and spontaneous tumor cell dissemination in vivo in a human melanoma animal
      metastasis model. These data are compatible with a model wherein interaction of
      MDA-9/syntenin with c-Src promotes the formation of an active FAK/c-Src signaling
      complex, leading to enhanced tumor cell invasion and metastatic spread. These
      provocative findings highlight mda-9/syntenin and its interacting partners as
      promising therapeutic targets for intervention of metastasis.

PMID- 18832468
TI  - Interplay of beta2* nicotinic receptors and dopamine pathways in the control of
      spontaneous locomotion.
AB  - Acetylcholine (ACh) is a known modulator of the activity of dopaminergic
      (DAergic) neurons through the stimulation of nicotinic ACh receptors (nAChRs).
      Yet, the subunit composition and specific location of nAChRs involved in DA
      mediated locomotion remain to be established in vivo. Mice lacking the beta2
      subunit of nAChRs (beta2KO) display striking hyperactivity in the open field,
      which suggests an imbalance in DA neurotransmission. Here, we performed the
      selective gene rescue of functional beta2*-nAChRs in either the substantia nigra
      pars compacta (SNpc) or the ventral tegmental area (VTA) of beta2KO mice. SNpc
      rescued mice displayed normalization of locomotor activity, both in familiar and
      unfamiliar environments, whereas restoration in the VTA only rescued exploratory
      behavior. These data demonstrate the dissociation between nigrostriatal and
      mesolimbic beta2*-nAChRs in regulating unique locomotor functions. In addition,
      the site-directed knock-down of the beta2 subunit in the SNpc by RNA interference
      caused hyperactivity in wild-type mice. These findings highlight the crucial
      interplay of nAChRs over the DA control of spontaneous locomotion.

PMID- 18832469
TI  - Dissociation of in vitro DNA deamination activity and physiological functions of
      AID mutants.
AB  - Activation-induced cytidine deaminase (AID) is essential for the DNA cleavage
      that initiates both somatic hypermutation (SHM) and class switch recombination
      (CSR) of the Ig gene. Two alternative mechanisms of DNA cleavage by AID have been
      proposed: RNA editing and DNA deamination. In support of the latter, AID has DNA
      deamination activity in cell-free systems that is assumed to represent its
      physiological function. To test this hypothesis, we generated various mouse AID
      mutants and compared their DNA deamination, CSR, and SHM activities. Here, we
      compared DNA deamination, CSR, and SHM activities of various AID mutants and
      found that most of their CSR or SHM activities were disproportionate with their
      DNA deamination activities. Specifically, we identified a cluster of mutants
      (H48A, L49A, R50A, and N51A) with low DNA deamination activity but relatively
      intact CSR activity. Of note is an AID mutant (N51A) that retained CSR function
      but lost DNA deamination activity. In addition, an APOBEC1 mutation at N57,
      homologous to N51 of AID, also abolished DNA deamination activity but retained
      RNA editing activity. These results indicate that DNA deamination activity does
      not represent the physiological function of AID.

PMID- 18832470
TI  - Shaping a bacterial genome by large chromosomal replacements, the evolutionary
      history of Streptococcus agalactiae.
AB  - Bacterial populations are subject to complex processes of diversification that
      involve mutation and horizontal DNA transfer mediated by transformation,
      transduction, or conjugation. Tracing the evolutionary events leading to genetic
      changes allows us to infer the history of a microbe. Here, we combine
      experimental and in silico approaches to explore the forces that drive the genome
      dynamics of Streptococcus agalactiae, the leading cause of neonatal infections.
      We demonstrate that large DNA segments of up to 334 kb of the chromosome of S.
      agalactiae can be transferred through conjugation from multiple initiation sites.
      Consistently, a genome-wide map analysis of nucleotide polymorphisms among eight
      human isolates demonstrated that each chromosome is a mosaic of large chromosomal
      fragments from different ancestors suggesting that large DNA exchanges have
      contributed to the genome dynamics in the natural population. The analysis of the
      resulting genetic flux led us to propose a model for the evolutionary history of
      this species in which clonal complexes of clinical importance derived from a
      single clone that evolved by exchanging large chromosomal regions with more
      distantly related strains. The emergence of this clone could be linked to
      selective sweeps associated with the reduction of genetic diversity in three
      regions within a large panel of human isolates. Up to now sex in bacteria has
      been assumed to involve mainly small regions; our results define S. agalactiae as
      an alternative paradigm in the study of bacterial evolution.

PMID- 18832471
TI  - Seminal oligouridinosis: low uridine secretion as a biomarker for infertility in
      spinal neurotrauma.
AB  - BACKGROUND: Compromised sexual health is a major rehabilitative barrier for men
      with lower-spinal cord injury (SCI). Although studies have revealed decreased
      sperm motility, the quantitative biochemical changes that underlie the
      infertility mechanism remain poorly understood. METHODS: We employed a
      nontargeted approach combining 800 MHz hydrogen nuclear magnetic resonance ((1)H
      NMR) spectroscopy and ultra-performance liquid chromatography-mass spectrometry
      (UPLC-MS) with pattern recognition methods to analyze seminal fluid metabolite
      profiles in 10 men with and 8 without SCI above thoracic vertebra 10 (T10).
      RESULTS: The metabolic phenotype for SCI could be predicted from the (1)H NMR
      data. The median concentration of uridine in fertile controls was 1.55 mmol/L
      (range 1.0-5.0 mmol/L), but was undetectable by both NMR and MS in all but 2
      individuals from the SCI group, one who later fathered a child without assisted
      fertility techniques. CONCLUSIONS: We hypothesize that uridine is likely to be an
      essential precursor to metabolites required for capacitation and is a potential
      marker for the prognosis of post-SCI functional fertility recovery. We derived
      the term "seminal oligouridinosis" to describe this newly identified condition.

PMID- 18832472
TI  - Association of lipoprotein-associated phospholipase A2 mass and activity with
      coronary and aortic atherosclerosis: findings from the Dallas Heart Study.
AB  - BACKGROUND: Our aim was to characterize the association of lipoprotein-associated
      phospholipase A(2) (Lp-PLA(2)) with coronary and aortic atherosclerosis in a
      large population-based study. METHODS: Lp-PLA(2) mass and activity were measured
      in 2171 subjects 30-65 years old participating in the Dallas Heart Study. We
      examined the association of Lp-PLA(2) levels with 3 atherosclerosis phenotypes:
      coronary artery calcium (CAC) measured by electron-beam computed tomography and
      abdominal aortic plaque (AAP) and aortic wall thickness (AWT) measured by
      magnetic resonance imaging. RESULTS: CAC and AAP were detected in 21% and 40% of
      subjects, respectively, and mean AWT (SD) was 1.70 (0.32) mm. In univariable
      analyses, Lp-PLA(2) mass (but not activity) was higher in both men (P = 0.04) and
      women (P = 0.02) with detectable CAC. Lp-PLA(2) mass and activity were higher (P
      = 0.004 and P = 0.01, respectively) and AWT was greater (P < 0.001 and P = 0.02,
      respectively) in women with aortic atheroma, but not in men. After adjustment for
      traditional atherosclerosis risk factors and C-reactive protein concentrations,
      Lp-PLA(2) mass and activity were not associated with AAP or AWT in either sex,
      but Lp-PLA(2) mass remained modestly associated with detectable CAC only in men
      (odds ratio 1.20 per 1 standard deviation increase, 95% CI 1.01-1.42, P = 0.04).
      CONCLUSIONS: Although Lp-PLA(2) mass was independently associated with CAC in
      men, it was not associated with AAP or AWT in men or with any of the
      atherosclerosis phenotypes in women. These findings suggest that if Lp-PLA(2)
      independently influences clinical events, it does so by promoting atherosclerotic
      plaque instability rather than by stimulating atherogenesis.

PMID- 18832473
TI  - Newborn screening for sickle cell disease using tandem mass spectrometry.
AB  - BACKGROUND: Neonatal screening programs for sickle cell disease are now
      widespread in North American and European countries. Most programs apply
      isoelectric focusing or HPLC to detect hemoglobin variants. Because tandem mass
      spectrometry (MS/MS) is being used for screening of inherited metabolic disorders
      and allows protein identification, it was worth testing for hemoglobinopathy
      screening. METHODS: We minimized sample preparation and analysis times by
      avoiding prior purification, derivatization, or separation. We developed a
      tryptic digestion methodology to screen for the main clinically important
      variants (Hb S, Hb C, and Hb E) and beta-thalassemia. To ensure proper
      discrimination between homozygote and heterozygote variants, we selected 4
      transitions with good signal intensities for each specific peptide and calculated
      variant/Hb A ratios for each. Method validation included intra- and interseries
      variability, carryover, and limit of detection. We also performed a comparative
      study with isoelectric focusing results on 2082 specimens. RESULTS: Intraassay
      imprecision values (CVs) varied between 2.5% and 30.7%. Interassay CVs were
      between 6.3% and 23.6%. Carryover was <0.03%, and the limit of detection was
      fixed at 1% of Hb S. According to the MS/MS settings (detection of Hb S, Hb C, Hb
      E, and beta-globin production defects), the comparative study did not yield any
      discrepant results between the 2 techniques. CONCLUSIONS: MS/MS is a reliable
      method for hemoglobinopathy neonatal screening.

PMID- 18832474
TI  - Lipopolysaccharide-binding protein: a new biomarker for infectious endocarditis?
AB  - BACKGROUND: Infectious endocarditis (IE) is a bacterial infection of the
      endocardium. Diagnosis is based on results obtained from echocardiography, blood
      cultures, and molecular genetic screening for bacteria and on data for
      inflammatory markers such as the leukocyte (WBC) count and the C-reactive protein
      (CRP) concentration. The aim of the present study was to evaluate
      lipopolysaccharide-binding protein (LBP) as a supportive biomarker for the
      diagnosis and therapeutic monitoring of IE. METHODS: We measured LBP and CRP
      concentrations and WBC counts in 57 IE patients at hospital admission, 40
      patients with noninfectious heart valve diseases (HVDs), and 55 healthy blood
      donors. The progression of these 3 markers and the influence of cardiac surgery
      on them were evaluated in 29 IE patients and 21 control patients. RESULTS: Serum
      LBP concentrations were significantly higher in IE patients [mean (SD), 33.41
      (32.10) mg/L] compared with HVD patients [6.67 (1.82) mg/L, P < 0.0001] and
      healthy control individuals [5.61 (1.20) mg/L]. The progression in the LBP
      concentration during therapy of IE patients correlated with the changes in the
      CRP concentration. The 2 markers were equally influenced by antibiotic treatment
      and surgical intervention. CONCLUSIONS: Serial LBP measurement may provide an
      effective and useful tool for evaluating the response to therapy in IE patients.
      We found a strong correlation between LBP and CRP concentrations; LBP has a
      tendency to increase earlier in cases of reinfection.

PMID- 18832475
TI  - Quantitation of human cytochrome P450 2D6 protein with immunoblot and mass
      spectrometry analysis.
AB  - Accurate quantification of cytochrome P450 (P450) protein contents is essential
      for reliable assessment of drug safety, including the prediction of in vivo
      clearance from in vitro metabolism data, which may be hampered by the use of
      uncharacterized standards and existence of unknown allelic isozymes. Therefore,
      this study aimed to delineate the variability in absolute quantification of
      polymorphic CYP2D6 drug-metabolizing enzyme and compare immunoblot and nano
      liquid chromatography coupled to mass spectrometry (nano-LC/MS) methods in
      identification and relative quantification of CYP2D6.1 and CYP2D6.2 allelic
      isozymes. Holoprotein content of in-house purified CYP2D6 isozymes was determined
      according to carbon monoxide difference spectrum, and total protein was
      quantified with bicinchoninic acid protein assay. Holoprotein/total CYP2D6
      protein ratio was markedly higher for purified CYP2D6.1 (71.0%) than that
      calculated for CYP2D6.1 Supersomes (35.5%), resulting in distinct linear
      calibration range (0.05-0.50 versus 0.025-0.25 pmol) that was determined by
      densitometric analysis of immunoblot bands. Likewise, purified CYP2D6.2 and
      CYP2D6.10 and the CYP2D6.10 Supersomes all showed different holoprotein/total
      CYP2D6 protein ratios and distinct immunoblot linear calibration ranges. In
      contrast to immunoblot, nano-LC/MS readily distinguished CYP2D6.2 (R296C and
      S486T) from CYP2D6.1 by isoform-specific proteolytic peptides that contain the
      altered amino acid residues. In addition, relative quantitation of the two
      allelic isozymes was successfully achieved with label-free protein
      quantification, consistent with the nominated ratio. Because immunoblot and nano
      LC/MS analyses measure total P450 protein (holoprotein and apoprotein) in a
      sample, complete understanding of holoprotein and apoprotein contents in P450
      standards is desired toward reliable quantification. Our data also suggest that
      nano-LC/MS not only facilitates P450 quantitation but also provides genotypic
      information.

PMID- 18832476
TI  - Prediction of drug clearance by glucuronidation from in vitro data: use of
      combined cytochrome P450 and UDP-glucuronosyltransferase cofactors in alamethicin
      activated human liver microsomes.
AB  - Glucuronidation via UDP-glucuronosyltransferase (UGT) is an increasingly
      important clearance pathway. In this study intrinsic clearance (CL(int)) values
      for buprenorphine, carvedilol, codeine, diclofenac, gemfibrozil, ketoprofen,
      midazolam, naloxone, raloxifene, and zidovudine were determined in pooled human
      liver microsomes using the substrate depletion approach. The in vitro clearance
      data indicated a varying contribution of glucuronidation to the clearance of the
      compounds studied, ranging from 6 to 79% for midazolam and gemfibrozil,
      respectively. The CL(int) was obtained using either individual or combined
      cofactors for cytochrome P450 (P450) and UGT enzymes with alamethicin activation
      and in the presence and absence of 2% bovine serum albumin (BSA). In the presence
      of combined P450 and UGT cofactors, CL(int) ranged from 2.8 to 688 microl/min/mg
      for zidovudine and buprenorphine, respectively; the clearance was approximately
      equal to the sum of the CL(int) values obtained in the presence of individual
      cofactors. The unbound intrinsic clearance (CL(int, u)) was scaled to provide an
      in vivo predicted CL(int); the data obtained in the presence of combined
      cofactors resulted in 5-fold underprediction on average. Addition of 2% BSA to
      the incubation with both P450 and UGT cofactors reduced the bias in the clearance
      prediction, with 8 of 10 compounds predicted within 2-fold of in vivo values with
      the exception of raloxifene and gemfibrozil. The current study indicates the
      applicability of combined cofactor conditions in the assessment of clearance for
      compounds with a differential contribution of P450 and UGT enzymes to their
      elimination. In addition, improved predictability of microsomal data is observed
      in the presence of BSA, in particular for UGT2B7 substrates.

PMID- 18832477
TI  - Absolute difference of hepatobiliary transporter multidrug resistance-associated
      protein (MRP2/Mrp2) in liver tissues and isolated hepatocytes from rat, dog,
      monkey, and human.
AB  - We previously reported that hepatobiliary transporter multidrug resistance
      associated protein (MRP2/Mrp2) is considered to be the major cause of the
      interspecies differences detected by efflux of fluorescent substrates in isolated
      hepatocytes. In the present study, the interspecies differences of MRP2/Mrp2 were
      first evaluated by quantitative real-time polymerase chain reaction and Western
      blotting. The mRNA levels were able to distinguish the difference among species
      with a rank order comparable with the corresponding activities observed, whereas
      the extents of the differences remained unknown. The cross-reactions of MRP2/Mrp2
      protein of different species with anti-human MRP2 polyclonal antibody were found
      by Western blotting. However, because of the unknown binding affinity of antibody
      to MRP2/Mrp2 protein across species and lack of purified MRP2/Mrp2 proteins for
      calibration, the immunoblotting assay was excluded from the absolute
      quantification of MRP2/Mrp2 protein for multiple species. By using our newly
      developed liquid chromatography-tandem mass spectrometry quantification method,
      we were able to measure the absolute amount of MRP2/Mrp2 in liver tissues and
      isolated hepatocytes across species. Freshly isolated hepatocytes conserved
      MRP2/Mrp2 protein levels that are comparable with those in the liver tissues. The
      amount of Mrp2 in rat liver was approximately 10-fold higher than that in other
      species. Moreover, a significant loss of Mrp2 protein in the membrane fraction of
      rat cryopreserved hepatocytes was observed. Thus, the absolute differences of
      MRP2/Mrp2 levels in various species were determined, for the first time, by
      direct quantification. The results could potentially fill the translational gaps
      of in vitro/in vivo or preclinical species to human extrapolation of
      hepatobiliary elimination mediated by MRP2/Mrp2.

PMID- 18832478
TI  - Apixaban metabolism and pharmacokinetics after oral administration to humans.
AB  - The metabolism and disposition of [(14)C]apixaban, an orally bioavailable, highly
      selective, and direct acting/reversible factor Xa inhibitor, was investigated in
      10 healthy male subjects without (group 1, n=6) and with bile collection (group
      2, n=4) after a single 20-mg oral dose. Urine, blood, and feces samples were
      collected from all subjects. Bile samples were also collected for 3 to 8 h after
      dosing from group 2 subjects. There were no serious adverse events or
      discontinuations due to adverse effects. In plasma, apixaban was the major
      circulating component and O-demethyl apixaban sulfate, a stable and water-soluble
      metabolite, was the significant metabolite. The exposure of apixaban (C(max) and
      area under the plasma concentration versus time curve) in subjects with bile
      collection was generally similar to that in subjects without bile collection. The
      administered dose was recovered in feces (group 1, 56.0%; group 2, 46.7%) and
      urine (group 1, 24.5%; group 2, 28.8%), with the parent drug representing
      approximately half of the recovered dose. Biliary excretion represented a minor
      elimination pathway (2.44% of the administered dose) from group 2 subjects within
      the limited collection period. Metabolic pathways identified for apixaban
      included O-demethylation, hydroxylation, and sulfation of hydroxylated O-demethyl
      apixaban. Thus, apixaban is an orally bioavailable inhibitor of factor Xa with
      elimination pathways that include metabolism and renal excretion.

PMID- 18832479
TI  - Key amino acid residues responsible for the differences in substrate specificity
      of human UDP-glucuronosyltransferase (UGT)1A9 and UGT1A8.
AB  - Human UDP-glucuronosyltransferase (UGT)1A9 is one of the major isoforms in liver
      and extrahepatic tissues, catalyzing the glucuronidation of a variety of drugs,
      dietary constituents, steroids, fatty acids, and bile acids. UGT1A9 shows high
      amino acid homology with UGT1A7, UGT1A8, and UGT1A10 with overlapping substrate
      specificity. However, the affinities for substrates are different among them.
      Amino acid alignment analysis revealed that 14 amino acids, Cys3, Arg42, Lys91,
      Ala92, Tyr106, Gly111, Tyr113, Asp115, Asn152, Leu173, Leu219, His221, Arg222,
      and Glu241, are unique to UGT1A9 compared with UGT1A7, UGT1A8, and UGT1A10. In
      this study, we constructed expression systems in human embryonic kidney 293 cells
      for seven mutants (Mut) UGT1A9, Mut 1 (R42Q), Mut 2 (K91M, A92D), Mut 3 (Y106F,
      G111S, D115G), Mut 4 (N152A), Mut 5 (L173A), Mut 6 (L219F, H221Q, R222Y), and Mut
      7 (E241A), in which the amino acids were substituted to those of UGT1A8. Using
      these mutants, the effects of the amino acid changes on the activities of 4
      methylumbelliferone (4-MU), p-nitrophenol (p-NP), and 3-hydroxydesloratadine
      glucuronidations were investigated. For 4-MU and p-NP O-glucuronidations, Mut 1
      and Mut 4 exhibited higher K(m) values and Mut 3 and Mut 4 exhibited higher
      V(max) values compared with wild-type UGT1A9. It is interesting to note that only
      Mut 4 was active toward 3-hydroxydesloratadine O-glucuronidation that is specific
      for UGT1A8. The findings reveal that the residues Arg42 and Asn152 may have a
      large contribution to the difference in the substrate specificity with that of
      UGT1A8, although all of the unique amino acids of UGT1A9 would be collectively
      involved in the catalytic property.

PMID- 18832480
TI  - Role of enzymatic N-hydroxylation and reduction in flutamide metabolite-induced
      liver toxicity.
AB  - Flutamide is used for prostate cancer therapy but occasionally induces severe
      liver injury. Flutamide is hydrolyzed in the body into 5-amino-2
      nitrobenzotrifluoride (FLU-1) and then further oxidized. In our previous study, N
      hydroxy FLU-1 (FLU-1 N-OH) was detected in the urine of patients and exhibited
      cytotoxicity in rat primary hepatocytes. In the present study, we have assessed
      the roles of FLU-1 N-oxidation and hepatic glutathione (GSH) depletion in liver
      injury. FLU-1 (200 mg/kg p.o.) was administered to C57BL/6 mice for 5 days
      together with 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP) (3 mg/kg i.p.)
      for the first 3 days. Mice were fasted for the last 2 days to deplete hepatic
      GSH. Administration of FLU-1 alone did not affect serum alanine aminotransferase
      activities (ALT), whereas coadministration of FLU-1 and TCPOBOP significantly
      increased ALT in fasted mice but not in nonfasted mice. Microsomal FLU-1 N
      hydroxylation was enhanced approximately 5 times by TCPOBOP treatment. Flutamide
      metabolite-protein adducts were detected in liver microsomes incubated with FLU-1
      N-OH, but not with FLU-1 and flutamide, by immunoblotting using antiflutamide
      antiserum. In the presence of mouse liver cytosol, FLU-1 N-OH was reduced back
      into FLU-1. This enzymatic reduction required NAD(P)H as a cofactor. The
      reduction was enhanced by the coexistence of NAD(P)H and GSH, whereas it was
      markedly inhibited by allopurinol (20 microM). By using purified bovine xanthine
      oxidase, the reduction was observed in the presence of NAD(P)H. These results
      suggest that FLU-1 N-OH is involved in flutamide-induced hepatotoxicity and that
      cytosolic reduction of FLU-1 N-OH plays a major role in protection against
      flutamide-induced hepatotoxicity.

PMID- 18832481
TI  - Long-term effects of bupivacaine on cartilage in a rabbit shoulder model.
AB  - BACKGROUND: Previous investigations have reported on the chondrotoxicity of
      bupivacaine in short-term in vivo and in vitro models. This study was designed to
      provide additional information on the long-term effects of bupivacaine infusion
      on articular cartilage in an established rabbit shoulder model. HYPOTHESIS:
      Infusion of bupivacaine into the rabbit shoulder will have long-term deleterious
      effects on articular cartilage. STUDY DESIGN: Controlled laboratory study.
      METHODS: Thirty-six rabbits were randomized into 3 groups and were infused over
      48 hours with saline (S), bupivacaine alone (B), or bupivacaine with epinephrine
      (B+E) into the glenohumeral joint. Animals were sacrificed after 3 months, and
      tissue samples were analyzed with live/dead cell assay, proteoglycan (PG)
      synthesis and content assays, and conventional histological evaluation. RESULTS:
      No macroscopic or radiographic changes were detected in the infused shoulders.
      Sulfate uptake of infused shoulders relative to controls was elevated to 112% +/
      39% (S), 166% +/-67% (B), and 210% +/-127% (B+E). Statistical analysis of PG
      content demonstrated significantly increased levels in bupivacaine groups
      compared with saline. There were no significant differences among groups in cell
      count, percentage of living cells, or histological grade. CONCLUSIONS: No
      permanent impairment of cartilage function was detected 3 months after intra
      articular infusion of bupivacaine. Cartilage metabolism was increased, indicating
      a possible reparative response. This suggests that, at least in the model used,
      articular cartilage has the ability to recover from the chondrotoxic effects of
      bupivacaine infusion. Before extrapolating these results to human cartilage,
      other factors including underlying cartilage injury or disease, decreased
      chondrocyte density, and increased bupivacaine dosing need to be taken into
      account. Clinical Relevance Bupivacaine toxicity has recently been implicated in
      the development of chondrolysis after arthroscopic shoulder procedures, but these
      findings suggest that additional noxious stimuli might be required before
      permanent damage ensues.

PMID- 18832482
TI  - Re: patellar tendon or semitendinosus tendon autografts for anterior cruciate
      ligament reconstruction: a prospective, randomized study with a 7-Year follow-up.

PMID- 18832483
TI  - Re: complications of anterior cruciate ligament reconstruction with bone-patellar
      tendon-bone constructs: care and prevention.

PMID- 18832484
TI  - Re: kinematics and electromyography of landing preparation in vertical stop-jump:
      risks for noncontact anterior cruciate ligament injury.

PMID- 18832485
TI  - Published...Or perished?

PMID- 18832486
TI  - Trochlear contact pressures after straight anteriorization of the tibial
      tuberosity.
AB  - BACKGROUND: Anteromedialization of the tibial tuberosity has been shown to
      decrease mean total contact pressures of the lateral trochlea and to shift
      contact pressures to the medial trochlea. HYPOTHESIS: Modifying the
      anteromedialization osteotomy to a straight anteriorization osteotomy of the
      tibial tuberosity can decrease trochlear contact pressures without a resultant
      medial shift of forces to the medial trochlear contact area. STUDY DESIGN:
      Controlled laboratory study. METHODS: Ten cadavers were tested before and after
      straight anteriorization tibial tuberosity osteotomy by loading the extensor
      mechanism with 89.1 and 178.2 N at 0 degrees , 30 degrees , 60 degrees , and 90
      degrees of flexion following a validated patellofemoral joint loading protocol.
      Contact pressures were measured with electroresistive pressure sensors placed
      directly on the trochlea. RESULTS: The mean trochlear contact pressures after
      osteotomy decreased significantly (P < .05) for loads of 89.1 and 178.2 N at both
      30 degrees (23% and 20%, respectively) and 60 degrees (18.7% and 31.9%,
      respectively) of knee flexion. The peak contact pressures decreased significantly
      (P < .05) for loads of 89.1 and 178.2 N at 30 degrees (24.3% and 27.0%,
      respectively) and 60 degrees (31.9% and 24.5%, respectively) and for loads of
      89.1 N at 90 degrees (13.4%) of knee flexion. CONCLUSION: The authors
      demonstrated significantly decreased trochlear contact forces after straight
      anteriorization osteotomy of the tibial tuberosity, without a significant
      resultant medial shift of the center of force. CLINICAL RELEVANCE: Straight
      anteriorization of the tibial tuberosity may be a useful adjunct for patients
      with medial articular defects of the patellar or trochlea in whom
      anteromedialization would be otherwise contraindicated.

PMID- 18832487
TI  - Cyclical loading of coracoclavicular ligament reconstructions: a comparative
      biomechanical study.
AB  - BACKGROUND: Reconstruction for injuries to the acromioclavicular joint remains
      controversial. HYPOTHESIS: A coracoclavicular ligament reconstruction with a
      semitendinosus tendon would have superior performance to the classic
      coracoacromial ligament transfer with or without augmentation. STUDY DESIGN:
      Controlled laboratory study. METHODS: Five cadaveric shoulders were used to
      reconstruct the coracoclavicular ligaments with 3 methods: coracoacromial
      ligament transfer without augmentation, coracoacromial ligament transfer
      augmented with No. 5 Ethibond suture, and a semitendinosus tendon. Each
      reconstruction was cyclically loaded at 40 N to 80 N for 2500 cycles, then from
      40 N to 210 N for 2500 cycles, followed by loading to failure. The number of
      cycles to 50% and 100% loss of acromioclavicular joint reduction were recorded.
      RESULTS: During the 40 N to 80 N-loading cycle, the coracoacromial transfer
      without augmentation failed (15 +/- 16 cycles). The augmented coracoacromial
      ligament transfer and the semitendinosus reconstruction did not fail (P = .008).
      During the 40 N to 210 N-loading cycle, the augmented coracoacromial ligament
      transfer failed (207 +/- 399 cycles). The semitendinosus reconstruction survived
      through both loading cycles (P < .01). CONCLUSION: Coracoclavicular ligament
      reconstruction with a semitendinosus graft is a biomechanically superior
      construct in a cyclically loaded setting to a coracoacromial ligament transfer
      augmented with a No. 5 Ethibond suture. CLINICAL RELEVANCE: The semitendinosus
      graft is a strong, biologic option for reconstruction of the coracoclavicular
      ligaments.

PMID- 18832488
TI  - Effect of dapoxetine on the pharmacokinetics and hemodynamic effects of
      tamsulosin in men on a stable dose of tamsulosin.
AB  - The tolerability of dapoxetine, a short-acting selective serotonin reuptake
      inhibitor being developed for premature ejaculation, was evaluated when
      coadministered with tamsulosin. Adult men on a stable dose of tamsulosin were
      randomized to also receive dapoxetine 30 or 60 mg, or placebo, in a crossover
      design. Supine and standing vital signs were measured on days 1 and 7. Plasma
      samples were collected for measurement of tamsulosin, dapoxetine, and dapoxetine
      metabolites. Coadministration of dapoxetine with tamsulosin did not alter
      orthostatic profiles or affect the incidence of orthostatic hypotension.
      Tamsulosin and dapoxetine pharmacokinetics were not altered. Adverse events were
      reported by 5.4%, 10.9%, and 23.2% of participants receiving tamsulosin with
      placebo, dapoxetine 30 mg, and dapoxetine 60 mg, respectively. The most common
      adverse events were diarrhea, dizziness, headache, and nausea. Therefore,
      dapoxetine had no clinically important effects on the pharmacokinetics or
      orthostatic profile of tamsulosin in men on a stable tamsulosin regimen.

PMID- 18832489
TI  - Telling interviewers about sexual abuse: predictors of child disclosure at
      forensic interviews.
AB  - This study aims to identify characteristics that predict full disclosure by
      victims of sexual abuse during a forensic interview. Data came from agency files
      for 987 cases of sexual abuse between December 2001 and December 2003 from
      Children's Advocacy Centers (CACs) and comparison communities within four U.S.
      states. Cases of children fully disclosing abuse when interviewed were compared
      to cases of children believed to be victims who gave no or partial disclosures.
      The likelihood of disclosure increased when victims were girls, a primary
      caregiver was supportive, and a child's disclosure instigated the investigation.
      The likelihood of disclosure was higher for children who were older at abuse
      onset and at forensic interview (each age variable having an independent effect).
      Communities differed on disclosure rate, with no difference associated with
      having a CAC. Findings suggest factors deserving consideration prior to a
      forensic interview, including organizational and community factors affecting
      disclosure rates.

PMID- 18832490
TI  - Breakdown dead ahead.

PMID- 18832491
TI  - "A fool for a client?" Mental illness and the right of self-representation.
AB  - Does the Constitution require a trial court to allow an obviously impaired man to
      represent himself? This column discusses the recent U.S. Supreme Court decision
      in Indiana v. Edwards, which allows states to limit a defendant's right to self
      representation when the individual lacks the mental capacity to conduct a trial
      defense unless represented. Previous cases bearing on the decision are discussed,
      including Dusky v. U.S. in 1960, which set the standard for competence to stand
      trial; Faretta v. California in 1975, which established the right of criminal
      defendants to represent themselves; and Godinez v. Moran in 1993, which upheld
      the Dusky standard for trial-related competence.

PMID- 18832492
TI  - Rates and patterns of treatment seeking by individuals with mood and anxiety
      disorders.

PMID- 18832493
TI  - To lock or not to lock patients'rooms: the key to autonomy?
AB  - Many patients with schizophrenia experience prominent negative symptoms.
      Functional impairment often results in patients who remain in their rooms for
      most of the day. It has thus become common practice in many psychiatric wards to
      lock patients' rooms during much of the morning and afternoon hours to encourage
      participation in ward activities and treatment modalities. Within the context of
      a quality control evaluation, two self-report surveys were conducted among
      patients (N=20) and staff members (N=9) in Beer Yaakov, Israel: the first survey
      was given when the rooms were locked at certain times, and the second survey was
      given after the rooms had been unlocked for one week. Patients and staff members
      expressed differing views both before and after the week-long open-door policy
      (patients enjoyed the policy, whereas many staff did not). Behavior during the
      period of the open-door policy varied among patients. The authors discuss the
      ethical grounds of locking doors and whether it is a best practice in keeping
      with rehabilitation interests.

PMID- 18832494
TI  - Schizophrenia: a terminal disease?

PMID- 18832495
TI  - Transformation of the California mental health system: stakeholder-driven
      planning as a transformational activity.
AB  - OBJECTIVE: This study describes strategies developed by California counties to
      transform their mental health systems under the 2004 Mental Health Services Act
      (MHSA). This voter initiative places a 1% tax on annual incomes over $1 million;
      tax monies are earmarked to transform county-operated mental health services into
      systems that are oriented more toward recovery. MHSA implementation itself can be
      considered "transformational" by balancing greater standardization of mental
      health service delivery in the state with a locally driven planning process.
      METHODS: A qualitative content analysis of the three-year plans submitted by 12
      counties to receive funds under MHSA was conducted to identify common themes, as
      well as innovative approaches. These 12 (out of 58) counties were chosen to
      represent both small and large counties, as well as geographic diversity, and
      they represent 62.3% of the state population. RESULTS: This analysis showed that
      the state guidelines and local planning process generated consistency across
      counties in establishing full-service partnerships with a "whatever it takes"
      approach to providing goal-directed services and supports to consumers and their
      families. There was, however, little convergence around the specific strategies
      to achieve this vision, reflecting both the local planning process and a relative
      lack of clear policy and guidance on evidence-based practices. CONCLUSIONS: There
      are many obstacles to the successful implementation of these ambitious plans.
      However, the state-guided, but stakeholder-driven, transformation in California
      appears to generate innovative approaches to recovery-oriented services, involve
      consumers and family members in service planning and delivery, and build
      community partnerships that create new opportunities for consumers to meet their
      recovery goals.

PMID- 18832496
TI  - A comparison of clinician, youth, and parent beliefs about helpfulness of
      interventions for early psychosis.
AB  - OBJECTIVE: This study explored whether there are gaps between the beliefs of
      clinicians and those of young people and their parents about the appropriate
      interventions for early psychosis. METHODS: Postal surveys of 105 Australian
      general practitioners, 155 psychiatrists, 183 psychologists, and 106 mental
      health nurses asked about the likely helpfulness of a wide range of potential
      interventions, covering helping professions, medications, psychological
      interventions, complementary interventions, and self-help. The results from these
      clinicians were compared with data from a national telephone survey of 968
      Australian youths (ages 12-25 years) and 531 of their parents. RESULTS: Young
      people and their parents were less likely than the clinicians to endorse the
      helpfulness of seeing a psychiatrist, using mental health services, and taking
      antipsychotic medication. On the other hand, young people and their parents were
      more likely to endorse informal social supports, generic counseling, and general
      stress reduction methods. CONCLUSIONS: The gap in intervention beliefs may be a
      contributor to delays in seeking professional help and adherence to treatment.
      Efforts are needed to improve public knowledge about psychosis treatment and to
      change mental health services so that they better meet consumer expectations.

PMID- 18832497
TI  - Meta-analysis of major depressive disorder relapse and recurrence with second
      generation antidepressants.
AB  - OBJECTIVE: This meta-analysis reviewed data on the efficacy and effectiveness of
      second-generation antidepressants for preventing major depression relapse and
      recurrence during continuation and maintenance phases of treatment, respectively.
      METHODS: MEDLINE, EMBASE, and PsycINFO, the Cochrane Library, and International
      Pharmaceutical Abstracts were searched for the period of January 1980 through
      April 2007 for reviews, randomized controlled trials, meta-analyses, and
      observational studies on the topic. Two persons independently reviewed abstracts
      and full-text articles using a structured data abstraction form to ensure
      consistency in appraisal and data extraction. RESULTS: Four comparative trials
      and 23 placebo-controlled trials that addressed relapse or recurrence prevention
      were included. Results of comparative trials have not demonstrated statistically
      significant differences between duloxetine and paroxetine, fluoxetine and
      sertraline, fluvoxamine and sertraline, and trazodone and venlafaxine. Pooled
      data for the class of second-generation antidepressants compared with placebo
      suggested a relatively large effect size that persists over time. For preventing
      both relapse and recurrence, the number of patients needed to treat is five (95%
      confidence interval of 4 to 6). Differences in the length of open-label treatment
      before randomization, drug type, and trial duration did not affect pooled
      estimates of relapse rates. Across all trials, 7% of patients randomly assigned
      to receive active treatment and 5% of patients randomly assigned to receive a
      placebo discontinued treatment because of adverse events. CONCLUSIONS: This
      review demonstrates the overall benefits of continuation- and maintenance-phase
      treatment of major depression with second-generation antidepressants and
      emphasizes the need for additional studies of comparative differences among
      drugs.

PMID- 18832498
TI  - Antidepressant use in black and white populations in the United States.
AB  - OBJECTIVE: The study objective was to estimate the prevalence and correlates of
      antidepressant use by black and white Americans. METHODS: Data from the
      Collaborative Psychiatric Epidemiology Surveys (CPES) were analyzed to calculate
      nationally representative estimates of past-year antidepressant use by black and
      white Americans ages 18 years and older (N=9,723). RESULTS: Among individuals
      with depressive and anxiety disorders in the past year (N=516), black respondents
      (14.6%) had significantly lower (p<.001) antidepressant use than white
      respondents (32.4%). Depression severity was significantly associated with higher
      antidepressant use for white but not for black respondents. Psychiatric disorders
      and vascular disease significantly increased the odds of past-year antidepressant
      use. The increased prevalence of antidepressant use associated with vascular
      disease was independent of diagnosable psychiatric disorders. Among respondents
      not meeting criteria for depressive and anxiety disorders in the past year,
      lifetime depressive and anxiety disorders and vascular disease significantly
      increased the odds of antidepressant use. CONCLUSIONS: Few white and fewer black
      Americans with depressive and anxiety disorders received antidepressant
      treatment. Higher depression severity was associated with more antidepressant use
      for white but not for black respondents. Antidepressant use was associated with
      medical conditions related to vascular disease, and these medical conditions were
      independent of coexisting psychiatric conditions. The results also indicate that
      many antidepressants are used for maintenance pharmacotherapy for depressive and
      anxiety disorders as well as common medical conditions associated with vascular
      disease.

PMID- 18832499
TI  - Guideline-consistent antidepressant treatment patterns among veterans with
      diabetes and major depressive disorder.
AB  - OBJECTIVE: This study estimated guideline-consistent antidepressant treatment of
      depression among veterans with diabetes and examined its variation by patient
      level demographic characteristics, socioeconomic characteristics, access to care,
      and health status. METHODS: Data were retrospectively analyzed from Veterans
      Health Administration (VHA) and Medicare claims of VHA clinic users with diabetes
      and major depressive disorder (N=3,953). Major depression was identified by using
      ICD-9-CM codes 296.2 and 296.3. Incident episode was identified by using 120-day
      negative diagnosis and medication history on or before the first depression
      diagnosis date in fiscal year 1999. Guideline-consistent depression treatment was
      defined as the receipt of antidepressants for at least 90 days within a period of
      six months after the onset of depression. Chi square tests and logistic
      regressions were used to analyze patterns of guideline-consistent antidepressant
      treatment. RESULTS: Overall, 51% received any antidepressant treatment for
      diagnosed major depression; among patients using any antidepressants, 62%
      received guideline-consistent antidepressant treatment. VHA users who received
      care from a mental health specialist were more likely to have guideline
      consistent treatment than those who were not receiving care from a mental health
      specialist. African Americans, older veterans, and those with substance use
      disorders were less likely to have guideline-consistent antidepressant treatment.
      CONCLUSIONS: Guideline-consistent depression care was lower for certain subgroups
      of individuals. Further research is necessary to evaluate the reasons for this
      finding, so that targeted care coordination strategies could be developed to
      improve antidepressant treatment. Increased contact with mental health specialty
      staff, which is now being implemented in the VHA, may increase antidepressant
      treatment among VHA users with diabetes and major depression.

PMID- 18832500
TI  - Systematic use of patient-rated depression severity monitoring: is it helpful and
      feasible in clinical psychiatry?
AB  - OBJECTIVE: The gap between evidence-based treatments and routine care has been
      well established. Findings from the Sequenced Treatments Alternatives to Relieve
      Depression (STAR*D) emphasized the importance of measurement-based care for the
      treatment of depression as a key ingredient for achieving response and remission;
      yet measurement-based care approaches are not commonly used in clinical practice.
      METHODS: The Nine-Item Patient Health Questionnaire (PHQ-9) for monitoring
      depression severity was introduced in 19 diverse psychiatric practices. During
      the one-year course of the project the helpfulness and feasibility of
      implementation of PHQ-9 in these psychiatric practices were studied. The project
      was modeled after the Institute for Healthcare Improvement Breakthrough Series.
      Two of the 19 practices dropped out during the course of the project. RESULTS: By
      the conclusion of the study, all remaining 17 practices had adopted PHQ-9 as a
      routine part of depression care in their practice. On the basis of responses from
      17 psychiatrists from those practices, PHQ-9 scores influenced clinical decision
      making for 93% of 6,096 patient contacts. With the additional information gained
      from the PHQ-9 score, one or more treatment changes occurred during 40% of these
      clinical contacts. Changing the dosage of antidepressant medication and adding
      another medication were the most common treatment changes recorded by
      psychiatrists, followed by starting or increasing psychotherapy and by switching
      or initiating antidepressants. In 3% of the patient contacts, using the PHQ-9 led
      to additional suicide risk assessment. CONCLUSIONS: The study findings suggest
      that adopting measurement-based care, such as using the PHQ-9, is achievable,
      even in practices with limited resources.

PMID- 18832501
TI  - Pharmacists' role in depression care: a survey of attitudes, current practices,
      and barriers.
AB  - OBJECTIVE: Pharmacists may be well placed to take up a role in depression care,
      complementing the role of general practitioners. However, depression care is a
      relatively new role for pharmacists, and little is known of their attitudes,
      current practices, and barriers toward it. METHODS: A random sample of 200
      community pharmacists in Belgium was surveyed about the care of patients with
      depression in comparison with patients with other, physical conditions. RESULTS:
      The 69 pharmacists who responded to the survey generally endorsed a very positive
      attitude toward their potential role in depression care. This willingness was,
      however, not reflected in current practice, and fulfilling this role appeared to
      be more difficult with patients with depression in comparison with patients with
      other, physical conditions. A lack of training in mental health issues was the
      most important barrier reported. Cooperation with general practitioners in
      depression care was desired, but the current level of cooperation was rather low.
      CONCLUSIONS: For pharmacists to effectively take up depression care, perceived
      barriers need to be addressed through specific training programs and increased
      cooperation with general practitioners.

PMID- 18832502
TI  - Changing trends in pediatric antipsychotic use in Florida's Medicaid program.
AB  - OBJECTIVE: This study describes the changing trends in antipsychotic use among
      youths aged 18 years and younger and in age subgroups (zero to five, six to 12,
      and 13 to 18 years) in the Florida Medicaid program. METHODS: The study used
      Florida Medicaid claims data associated with approximately 1.2 million children
      and adolescent enrollees per year to describe monthly antipsychotic use from July
      2002 to December 2005. A preliminary examination of trends indicated that
      antipsychotic use might be different for the periods before May 2004 and after
      April 2004. For this reason, piecewise regression was used to compare the trends
      for these two periods. RESULTS: This study found significant increases in the use
      of antipsychotic medications for all three age groups from July 2002 to April
      2004. The greatest rate of growth was for the 13- to 18-year age group, and the
      least rate of growth was for the zero- to five-year age group. From May 2004 to
      December 2005 antipsychotic utilization trends were flat for youths age 18 years
      and younger and for the six- to 12-year and the 13- to 18-year age groups. For
      preschool-age children (the zero- to five-year age group), there was a slight but
      significant decline in antipsychotic use. Significant changes were also observed
      in the specific second-generation antipsychotic agents prescribed. Although
      risperidone remained the most frequently prescribed antipsychotic, its use
      declined significantly from May 2004 to December 2005. Olanzapine use also
      declined during this period. On the other hand, aripiprazole use increased
      significantly throughout the study period, with usage among the 13- to 18-year
      age group almost equaling that of risperidone by December 2005. CONCLUSIONS: The
      lack of growth in antipsychotic prescribing after the spring of 2004 represents a
      significant departure from historical trends. Although some in-state policies may
      have affected these trends, it appears that the timing and extent of the changes
      occurred shortly after the Food and Drug Administration required warnings on
      second-generation antipsychotic medications related to weight gain, glucose
      levels, and diabetes. They appeared immediately after the black box warning for
      pediatric antidepressant medications, and they appeared shortly after the Joint
      American Diabetes and American Psychiatric Association Consensus Statement. These
      factors suggest the existence of a prescribing community that is responsive to
      evidence and to professional and regulatory actions based on it.

PMID- 18832503
TI  - Trends in use of antipsychotics and mood stabilizers among Medicaid beneficiaries
      with bipolar disorder, 2001-2004.
AB  - OBJECTIVE: This study examined longitudinal trends in the use of mood stabilizers
      and antipsychotics for treatment of bipolar disorder in a large public mental
      health system and whether trends differed by age, gender, and race-ethnicity.
      METHODS: Data were from Medicaid beneficiaries with bipolar disorder receiving
      services in the San Diego County public mental health system from 2001 to 2004.
      For each year the proportion of clients receiving any pharmacotherapy and the
      proportion receiving antipsychotics alone, mood stabilizers alone, or
      antipsychotics plus mood stabilizers were determined. Pharmacotherapy use was
      examined by age, gender, and race-ethnicity. RESULTS: A total of 1,473 clients
      were identified who were continuously enrolled in Medicaid during the four years.
      Seventy-five percent received mood stabilizers or antipsychotics. Of this group,
      33% received antipsychotics alone, 23% mood stabilizers alone, and 44% both
      antipsychotics and mood stabilizers. The percentage receiving mood stabilizers or
      antipsychotics increased significantly, from 71% in 2001 to 77% in 2004,
      primarily because of increased use among women. Use of mood stabilizers alone
      declined from 25% to 20%, and use of antipsychotics alone increased from 32% to
      36%. African Americans and Latinos were less likely than non-Latino whites to
      receive mood stabilizers or antipsychotics; this pattern was stable over time.
      CONCLUSIONS: Antipsychotics were prescribed for a larger percentage of clients
      than mood stabilizers. Persons from ethnic minority groups were less likely to
      receive either medication type. Research is needed to examine factors affecting
      pharmacotherapy in bipolar disorder and mechanisms underlying racial-ethnic
      disparities in pharmacotherapy, including their persistence over time.

PMID- 18832504
TI  - Psychotropic medications for patients with bipolar disorder in the United States:
      polytherapy and adherence.
AB  - OBJECTIVE: Because treatments for bipolar disorder include a growing number of
      psychotropic agents, the authors evaluated psychotropic polytherapy and adherence
      to treatment among U.S. patients with bipolar disorder. METHODS: National health
      plan claims data (2000-2004) were used to identify patients diagnosed as having
      bipolar disorder who had continuous benefits and had not been prescribed
      medication for bipolar disorder for six months or more. The study compared drugs
      dispensed to these patients initially and at one year and characterized patients
      who were adherent to mood-stabilizers. RESULTS: A total of 7,406 patients had a
      bipolar disorder: bipolar I (55%), bipolar II (15%), or bipolar disorder not
      otherwise specified (30%). Women represented 57% of the sample; mean+/-SD age was
      35.4+/-12.4 years. Initial prescription fills involved one psychotropic agent in
      67% of patients, and two or more psychotropics (polytherapy) in 33%. Initial
      prescription drug selections involved: antidepressants > anticonvulsants >or=
      antipsychotics > sedatives > lithium; initial mood stabilizer use ranked:
      valproate > lithium > carbamazepine or oxcarbazepine > lamotrigine;
      antipsychotics ranked: olanzapine > quetiapine >or= risperidone > ziprasidone >
      aripiprazole > clozapine. Rankings were similar at one year, when only 31% of
      patients received monotherapy (a 2.2-fold decline), 32% received polytherapy, and
      37% received no psychotropics. Initially patients received 1.42 psychotropic
      drugs per person; at one year, patients received 175, and at both times
      polytherapy was less likely with lithium than with anticonvulsants. In
      multivariate modeling, one-year mood stabilizer use was greater with the
      following: older age, type of mood stabilizer (lamotrigine > valproate >
      carbamazepine or oxcarbazepine > lithium) and was associated with more
      psychiatric office and emergency visits, clinician type (more common with
      psychiatrists than with primary care physicians), and nonuse of off-label
      anticonvulsants. CONCLUSIONS: Polytherapy was used by one-third of patients
      initially and at one year, antidepressant use was highly prevalent initially and
      later, but lack of treatment was prevalent at one year. Plausible clinical and
      treatment factors were associated with sustained mood stabilizer adherence.

PMID- 18832505
TI  - Pharmacologic treatment of posttraumatic stress disorder among privately insured
      Americans.
AB  - OBJECTIVE: Although psychological trauma affects millions of Americans, few
      studies have examined treatment of posttraumatic stress disorder (PTSD) in real
      world service environments. This study explored pharmacological treatment of PTSD
      among privately insured individuals. METHODS: Data were from the MarketScan
      database, which compiles claims from private health insurance plans nationwide.
      Descriptive statistics and multivariate logistic regression were used to identify
      predictors of any use of a psychotropic medication and use of three medication
      classes: antidepressants, anxiolytics or sedative-hypnotics, and antipsychotics.
      RESULTS: Of 860,090 adult mental health care users in 2005, only 10,636 (1.2%)
      had a diagnosis of PTSD. Sixty percent of PTSD patients received any psychotropic
      medication: 74.3% of those received antidepressants, 73.7% received anxiolytics
      or sedative-hypnotics, and 21.3% received antipsychotics. Greater likelihood of
      any medication use was associated with greater use of mental health services and
      with several comorbid psychiatric disorders. Having a comorbid diagnosis of an
      indicated disorder was the most robust predictor of use of each of the three
      medication classes: major depressive disorder and dysthymia were most strongly
      associated with antidepressant use, schizophrenia and bipolar disorder were
      associated with antipsychotic use, and anxiety disorders were associated with use
      of anxiolytics or sedative-hypnotics. CONCLUSIONS: Psychotropic medications were
      frequently used in the treatment of PTSD among privately insured clients.
      Although use targeted specifically to PTSD and to comorbid disorders was common,
      substantial use appeared to be unrelated to diagnosis and may be targeted at
      specific symptoms rather than diagnosed illnesses. Further research is needed to
      determine symptom-specific responses to medications across diagnoses.

PMID- 18832506
TI  - The impact of Medicare Part D on psychotropic utilization and financial burden
      for community-based seniors.
AB  - OBJECTIVE: This study evaluated the impact of Medicare's new drug benefit (Part
      D) on utilization of psychotropic medications and the consequent financial burden
      for the elderly population. METHODS: The effect of Medicare Part D was measured
      by analyzing 24-month pharmacy claims collected from one of the largest retail
      pharmacy chains in the United States. Segmented regression analysis of
      interrupted time series was used to evaluate population-level changes in the
      utilization of the most commonly used psychotropic therapeutic categories among
      seniors, namely antidepressants, antipsychotics, and benzodiazepines. RESULTS: In
      the first-year implementation of Part D, the proportion of out-of-pocket payment
      in total pharmacy reimbursement decreased 18% for antidepressants (net savings of
      $4.52 per prescription) and 21% for antipsychotics (net savings of $5.71 per
      prescription). In contrast, the out-of-pocket share paid for benzodiazepines
      increased 19% (net increase of $2.79 per prescription). Part D was associated
      with significant month-to-month increase in use of antidepressants and
      antipsychotics. By December 2006, the antidepressant and antipsychotic
      prescriptions filled by seniors grew 7% (from 273,166 to 293,590 prescriptions
      per month, p<.001) and 18% (from 41,079 to 48,276 prescriptions per month,
      p<.001), respectively, compared with the expected level estimated from prior Part
      D trends. In contrast, Part D led to an immediate and sustained drop of 5% (from
      238,961 to 226,622 prescriptions per month, p<.001) in number of benzodiazepine
      prescriptions filled by seniors. CONCLUSIONS: Part D has improved access to
      psychotropic medications covered under plans by reducing out-of-pocket expenses.
      However, the financial burden related to excluded medications, such as
      benzodiazepines, has significantly increased.

PMID- 18832507
TI  - Eliminating seclusion and restraint in recovery-oriented crisis services.
AB  - The use of seclusion and physical restraint is viewed as a practice incompatible
      with the vision of recovery, and its therapeutic benefit remains unsubstantiated.
      This Open Forum describes an initiative that began in 1999 at two crisis centers
      that was designed to completely eliminate the practice of seclusion and
      restraint. Seclusion and restraint elimination strategies included strong
      leadership direction, policy and procedural change, staff training, consumer
      debriefing, and regular feedback on progress. Existing records indicated that
      over a 58-month follow-up period (January 2000 to October 2004), the larger
      crisis center took ten months until a month registered zero seclusions and 31
      months until a month recorded zero restraints. The smaller crisis center achieved
      these same goals in two months and 15 months, respectively. The success of this
      initiative suggests that policy makers and organizational leaders familiarize
      themselves with these and other similar seclusion and restraint reduction
      strategies that now exist.

PMID- 18832508
TI  - How Medicaid agencies administer mental health services: results from a 50-state
      survey.
AB  - OBJECTIVE: This brief report describes some notable variations in how state
      Medicaid agencies administer and fund Medicaid mental health services. METHODS:
      Hour-long telephone interviews were conducted with all state and District of
      Columbia Medicaid directors or their designees. RESULTS: Responses indicated that
      Medicaid and mental health agencies were located within the same umbrella agency
      in 28 states, potentially facilitating collaboration. The mental health agency
      provided funding for some Medicaid mental health services in 32 states, and
      counties provided such funding in 22 states. Medicaid agencies generally
      delegated more authority to state mental health agencies in states where some
      Medicaid funding came from mental health sources and also in states where both
      agencies were in the same umbrella agency. CONCLUSIONS: The increasing role of
      Medicaid in funding state mental health services, combined with new federal
      limits on Medicaid financing of these services, underscores the importance of
      interagency collaboration and better alignment of Medicaid and mental health
      responsibilities.

PMID- 18832509
TI  - Dosing frequency and adherence to antipsychotic medications.
AB  - OBJECTIVES: This study investigated whether dosing frequency affects
      antipsychotic medication adherence among patients with schizophrenia. METHODS:
      Databases from the Department of Veterans Affairs were used to assess adherence
      among patients with a diagnosis of schizophrenia. Adherence was measured by using
      antipsychotic medication possession ratios (MPRs). Adherence was compared among
      patients who experienced an increase or decrease in dosing frequency and among
      patients on stable regimens of once-daily or more than once-daily dosing.
      RESULTS: Among patients with a dose increase (N=1,639), those with increases in
      dosing frequency (N=258) had a mean change in MPRs of -.105, compared with -.002
      for those without a dosing frequency change (N=1,381) (p<.001). Patients with
      decreases in dosing frequency (N=1,370) had a small but significant increase in
      mean MPRs (MPR change=.045) when compared with 2,740 patients without a dosing
      frequency change (MPR change=-.018) (p<.001). Among patients on stable regimens
      (N=32,612), there were no significant differences in MPRs between those receiving
      once-daily dosing (MPR=.80) and those receiving more than once-daily dosing
      (MPR=.80). CONCLUSIONS: Among patients on less stable dosing regimens, increases
      in dosing frequency may result in modest decreases in adherence.

PMID- 18832510
TI  - Predictors of major depression six months after admission for outpatient
      treatment.
AB  - OBJECTIVE: This study examined the rate and predictors of major depression six
      months after outpatient mental health admission. METHODS: Assessments were
      conducted at admission and three and six months later among 166 participants.
      Antidepressant treatment adequacy and depression outcomes were assessed at follow
      ups. RESULTS: Predictors of major depression at six months included nonremission
      status at three months (odds ratio [OR]=3.56, p=.003), inadequacy of early
      pharmacotherapy (OR=2.73, p=.009), worse physical functioning measured by the 36
      Item Short-Form Health Survey (OR=.975, p<.001), and being unmarried (OR=2.54,
      p=.031). CONCLUSIONS: The findings support the effects of baseline physical
      disability, marital status, early treatment adequacy, and early remission on the
      course of major depression. The identification of individuals who do not receive
      intensive pharmacotherapy or who have not recovered by three months may provide
      opportunities for interventions to optimize six-month outcomes and to prevent the
      development of a persistent depression.

PMID- 18832511
TI  - Treating obesity: interventions in an inner-city population.

PMID- 18832512
TI  - One-session music therapy and CBT for critically ill cancer patients.

PMID- 18832513
TI  - Treatment of opioid dependence via home-based telepsychiatry.

PMID- 18832514
TI  - The wellness model.

PMID- 18832515
TI  - "Trumping rules" affect diagnoses of persons with severe mental illness.

PMID- 18832516
TI  - Attitudes of patients and families toward restraint and seclusion.

PMID- 18832517
TI  - Team negotiation: social, epistemic, economic, and psychological consequences of
      subgroup conflict.
AB  - Large collectives (e.g., organizations, political parties, nations) are seldom
      unitary players. Rather, they consist of different subgroups that often have
      conflicting interests. Nonetheless, negotiation research consistently regards
      negotiating teams, who represent these collectives, as monolithic parties with
      uniform interests. This article integrates concepts from social psychology,
      management, political science, and behavioral game theory to explore the effects
      of subgroup conflict on team negotiation. Specifically, the present research
      introduced a conflict of interests within negotiating teams and investigated how
      this internal conflict affects the outcome of the negotiation between teams. An
      experiment with 80 four-person teams found that conflict between subgroups had a
      detrimental effect on the performance of negotiating teams. This research also
      employed a recent model of motivated information processing in groups to
      investigate possible processes underlying the effect of subgroup conflict on team
      negotiation.

PMID- 18832518
TI  - Long-term outcome of treatment with infliximab in 614 patients with Crohn's
      disease: results from a single-centre cohort.
AB  - BACKGROUND AND AIMS: This observational study assessed the long-term clinical
      benefit of infliximab (IFX) in 614 consecutive patients with Crohn's disease (CD)
      from a single centre during a median follow-up of 55 months (interquartile range
      (IQR) 27-83). METHODS: The primary analysis looked at the proportion of patients
      with initial response to IFX who had sustained clinical benefit at the end of
      follow-up. The long-term effects of IFX on the course of CD as reflected by the
      rate of surgery and hospitalisations and need for corticosteroids were also
      analysed. RESULTS: 10.9% of patients were primary non-responders to IFX.
      Sustained benefit was observed in 347 of the 547 patients (63.4%) receiving long
      term treatment. In 68.3% of these, treatment with IFX was ongoing and in 31.7%
      IFX was stopped, with the patient being in remission. Seventy patients (12.8%)
      had to stop IFX due to side effects and 118 (21.6%) due to loss of response.
      Although the yearly drop-out rates of IFX in patients with episodic (10.7%) and
      scheduled treatment (7.1%) were similar, the need for hospitalisations and
      surgery decreased less in the episodic than in the scheduled group. Steroid
      discontinuation also occurred in a higher proportion of patients in the scheduled
      group than in the episodic group. CONCLUSIONS: In this large real-life cohort of
      patients with CD, long-term treatment with IFX was very efficacious to maintain
      improvement during a median follow-up of almost 5 years and changed disease
      outcome by decreasing the rate of hospitalisations and surgery.

PMID- 18832519
TI  - CpG island methylator phenotype, microsatellite instability, BRAF mutation and
      clinical outcome in colon cancer.
AB  - BACKGROUND: The CpG island methylator phenotype (CIMP), characterised by
      widespread promoter methylation, is associated with microsatellite instability
      (MSI) and BRAF mutation in colorectal cancer. The independent effect of CIMP, MSI
      and BRAF mutation on prognosis remains uncertain. METHODS: Utilising 649 colon
      cancers (stage I-IV) in two independent cohort studies, we quantified DNA
      methylation in eight CIMP-specific promoters (CACNA1G, CDKN2A (p16), CRABP1,
      IGF2, MLH1, NEUROG1, RUNX3 and SOCS1) as well as CHFR, HIC1, IGFBP3, MGMT, MINT1,
      MINT31, p14, and WRN by using MethyLight technology. We examined MSI, KRAS and
      BRAF status. Cox proportional hazard models computed hazard ratios (HRs) for
      colon cancer-specific and overall mortalities, adjusting for patient
      characteristics and tumoral molecular features. RESULTS: After adjustment for
      other predictors of patient survival, patients with CIMP-high cancers (126 (19%)
      tumours with >or=6/8 methylated CIMP-specific promoters) experienced a
      significantly low colon cancer-specific mortality (multivariate HR 0.44, 95%
      confidence interval (CI) 0.22 to 0.88), whereas the BRAF mutation was
      significantly associated with a high cancer-specific mortality (multivariate HR
      1.97, 95% CI 1.13 to 3.42). A trend toward a low cancer-specific mortality was
      observed for MSI-high tumours (multivariate HR 0.70, 95% CI 0.36 to 1.37). In
      stratified analyses, CIMP-high tumours were associated with a significant
      reduction in colon cancer-specific mortality, regardless of both MSI and BRAF
      status. The relation between CIMP-high and lower mortality appeared to be
      consistent across all stages. KRAS mutation was unrelated to prognostic
      significance. CONCLUSION: CIMP-high appears to be an independent predictor of a
      low colon cancer-specific mortality, while BRAF mutation is associated with a
      high colon cancer-specific mortality.

PMID- 18832521
TI  - Early preservation of effector functions followed by eventual T cell memory
      depletion: a model for the delayed onset of the effect of thiopurines.
AB  - OBJECTIVE: The onset of the effect of thiopurines is delayed for several months.
      The aim of this study was to investigate immune mechanisms for this delay.
      METHODS: The effects of thiopurines on human peripheral blood T cells and on
      lamina propria lymphocytes were investigated for apoptosis induction by Annexin
      V/propidium iodide (PI) and for cytokine secretion by intracellular staining and
      ELISA assays. To investigate the mechanism of the effect of thiopurines in vivo,
      Balb/C mice were co-immunised with HEL/OVA (hen egg lysozyme/ovalbumin) antigens,
      and then repeatedly challenged by HEL only, while being treated by mercaptopurine
      or vehicle alone for either 4 or 20 weeks. The memory response of CD4+
      splenocytes towards HEL/OVA was then determined by CFSE (carboxyfluorescein
      succinimidyl ester) dilution. RESULTS: Thiopurines arrested the proliferation of
      stimulated T cells but did not enhance the apoptosis of either resting T cells or
      activated T cells until day 5 poststimulation. Despite the proliferation arrest,
      stimulated T cells successfully differentiated into effector cells, as evidenced
      by their capacity for proinflammatory cytokine secretion, potent adhesion and
      cytotoxicity. Prolonged mercaptopurine treatment of mice for 20 weeks selectively
      reduced the CD4+ memory response to a repeatedly encountered HEL antigen, but did
      not affect the T cell memory pool to the previously presented OVA antigen. A
      shorter, 4 weeks, treatment with mercaptopurine did not inhibit the memory
      response to either antigen. CONCLUSIONS: T cells arrested from cycling by
      thiopurines can still differentiate into potent effector cells capable of
      propagating the inflammatory process. Thiopurine treatment results in depletion
      of antigen-specific memory T cells, but this effect is dependent upon repeated
      encounters with the antigen over a prolonged time course.

PMID- 18832522
TI  - Metabolic syndrome increases the risk of liver cirrhosis in chronic hepatitis B.
AB  - BACKGROUND: Metabolic syndrome is associated with non-alcoholic steatohepatitis
      and cryptogenic cirrhosis. Whether metabolic syndrome affects the severity of
      chronic hepatitis B (CHB) is unclear. AIM: We aimed to study the relationship
      between metabolic syndrome and the risk of liver cirrhosis in patients with CHB.
      METHODS: We prospectively recruited patients with CHB from primary care and
      hospital clinics for liver stiffness measurement (LSM) with transient
      elastography to diagnose early cirrhosis. Probable cirrhosis was defined as LSM
      >or=13.4 kPa. We analysed a subgroup of patients with paired LSM and liver
      biopsies to validate the accuracy of LSM. RESULTS: 1466 patients had reliable LSM
      and 134 (9%) patients had adequate liver biopsy. 188 (13%) patients had metabolic
      syndrome. Histological liver cirrhosis was present in 32/134 (24%) patients.
      Histological liver cirrhosis was more common among patients who had metabolic
      syndrome (38%) versus those who did not (11%, p<0.001). The specificity of
      probable cirrhosis on LSM for histological cirrhosis was 94%. Probable cirrhosis
      was present in 187 (13%) patients. Metabolic syndrome was more prevalent in
      patients with probable cirrhosis (24%) than those without cirrhosis (11%,
      p<0.001). After adjustment for anthropometric, biochemical and virological
      factors, metabolic syndrome remained an independent factor associated with
      probable cirrhosis (odds ratio 1.7, 95% confidence interval (CI) 1.1 to 2.6). The
      odds ratios of probable cirrhosis were 1.4 (95% CI, 0.9 to 2.3), 2.6 (95% CI, 1.7
      to 4.3), 4.1 (95% CI, 2.4 to 7.1), 4.0 (95% CI, 1.9 to 8.4) and 5.5 (95% CI, 1.8
      to 16.7) in patients with one, two, three, four and five components of metabolic
      syndrome, respectively. CONCLUSION: Metabolic syndrome is an independent risk
      factor of liver cirrhosis in CHB.

PMID- 18832520
TI  - Once daily versus three times daily mesalazine granules in active ulcerative
      colitis: a double-blind, double-dummy, randomised, non-inferiority trial.
AB  - OBJECTIVES: To determine the therapeutic equivalence and safety of once daily
      (OD) versus three times daily (TID) dosing of a total daily dose of 3 g Salofalk
      (mesalazine) granules in patients with active ulcerative colitis. DESIGN: A
      randomised, double-blind, double-dummy, parallel group, multicentre,
      international, phase III non-inferiority study. SETTING: 54 centres in 13
      countries. PATIENTS: 380 patients with confirmed diagnosis of established or
      first attack of ulcerative colitis (clinical activity index (CAI)>4 and
      endoscopic index > or =4 at baseline) were randomised and treated. INTERVENTIONS:
      8-week treatment with either 3 g OD or 1 g TID mesalazine granules. MAIN OUTCOME
      MEASURES: Clinical remission (CAI< or =4) at study end. RESULTS: 380 patients
      were evaluable for efficacy and safety by intention-to-treat (ITT); 345 for per
      protocol (PP) analysis. In the ITT population, 79.1% in the OD group (n = 191)
      and 75.7% in the TID group (n = 189) achieved clinical remission (p<0.0001 for
      non-inferiority). Significantly more patients with proctosigmoiditis achieved
      clinical remission in the OD group (86%; n = 97) versus the TID group (73%; n =
      100; p = 0.0298). About 70% of patients in both treatment groups achieved
      endoscopic remission, and 35% in the OD group and 41% in the TID group achieved
      histological remission. About 80% of all patients preferred OD dosing. Similar
      numbers of adverse events occurred in 55 patients (28.8%) in the OD group and in
      61 patients (32.3%) in the TID group, indicating that the two dosing regimens
      were equally safe and well tolerated. CONCLUSIONS: OD 3 g mesalazine granules are
      as effective and safe as a TID 1 g schedule. With respect to the best possible
      adherence of patients to the treatment, OD dosing of mesalazine should be the
      preferred application mode in active ulcerative colitis.

PMID- 18832523
TI  - CD4+Foxp3+ regulatory T cell expansion induced by antigen-driven interaction with
      intestinal epithelial cells independent of local dendritic cells.
AB  - BACKGROUND: Regulatory T cells (T(regs)) have potential anti-inflammatory effects
      and are likely to be important in the pathogenesis of chronic inflammatory bowel
      disease (IBD). However, the induction and expansion of T(regs) at sites of
      mucosal inflammation are not yet fully understood and may involve antigen
      presentation by local dendritic cells (DCs) and/or intestinal epithelial cells
      (IECs). METHODS: To determine the unique ways in which the gut induces or expands
      T(regs), a transgenic mouse model that is based on the specific expression of a
      model autoantigen (influenza haemagglutinin (HA)) in the intestinal epithelium
      (VILLIN-HA) was used. Gut-associated DCs and IECs isolated from these mice were
      phenotypically and functionally characterised for the potential to interact with
      HA-specific T(regs) in vitro and in vivo. RESULTS: Intestinal self-antigen
      expression leads to peripheral expansion of antigen-specific CD4(+)Foxp3(+)
      T(regs). Although gut-associated DCs can induce antigen-specific CD4(+)Foxp3(+) T
      cell proliferation, in vivo depletion of DCs did not preclude proliferation of
      these cells. Interestingly, antigen presentation by primary IECs is sufficient to
      expand antigen-specific CD4(+)Foxp3(+) T(regs) efficiently. This is dependent on
      major histocompatibility complex class II, but, in contrast to DCs, is unlikely
      to require transforming growth factor beta and retinoic acid. CONCLUSION: This
      study provides experimental evidence for a new concept in mucosal immunity: in
      contrast to current thinking, expansion of T(regs) can be achieved independently
      of local DCs through antigen-specific IEC-T cell interactions.

PMID- 18832524
TI  - Long-term safety of infliximab for the treatment of inflammatory bowel disease: a
      single-centre cohort study.
AB  - BACKGROUND AND AIMS: This study evaluates the long-term safety of infliximab in
      patients with inflammatory bowel disease (IBD) treated with the drug over a 14
      year period. METHODS: The medical records of 734 patients with IBD treated with
      infliximab and 666 control patients not treated with infliximab were reviewed for
      adverse events. The time of onset and outcome, severity and concomitant
      medication were recorded. RESULTS: Patients and controls were followed up for
      serious adverse events for a median time of 58 months (IQR 33-88) and 144 months
      (IQR 83-163), respectively. 112 severe adverse events occurred in 93 patients
      (13%) treated with infliximab and 157 occurred in 126 (19%) control patients (OR
      1.33 (95% CI 0.56 to 3.00, p = 0.45). There was no difference between the two
      groups in mortality, malignancies and infection rate. Tuberculosis was diagnosed
      in two patients receiving infliximab who had negative skin tests at baseline
      whereas none of 16 patients with positive skin tests who received prophylaxis
      developed tuberculosis. Concomitant treatment with steroids was the only
      independent risk factor for infections in patients treated with infliximab (OR
      2.69 (95% CI 1.18 to 6.12), p = 0.018). The most commonly observed systemic side
      effects were skin eruptions including psoriasiform eruptions in 150 patients
      (20%). CONCLUSIONS: Long-term infliximab treatment had a good overall safety
      profile in the patient cohort studied.

PMID- 18832526
TI  - Puberty, contraception, and hormonal management for young people with
      disabilities.
AB  - Assessment and management of a young person with a severe disability is
      multifaceted and complex. Variations of puberty can cause major concerns for
      parents and carers, with fears of imminent menstruation, peer and personal
      differences, concern for height outcome, as well as grief for a loss of
      childhood. Addressing physical, emotional, and social issues assists in
      optimizing outcomes. This article outlines specific evaluation and detailed
      management strategies for female and male pubertal problems in the context of
      disability, including treatments for extreme pubertal delay or acceleration,
      menstrual management at different ages, contraceptive issues, and sexual function
      and choices for both sexes.

PMID- 18832525
TI  - Linkage of Crohn's disease-related serological phenotypes: NFKB1 haplotypes are
      associated with anti-CBir1 and ASCA, and show reduced NF-kappaB activation.
AB  - BACKGROUND AND AIMS: Genetics studies of the serum expression of antibodies to
      microbial antigens may yield important clues to the pathogenesis of Crohn's
      disease. Our aim was to conduct a linkage study using expression of anti-CBir1,
      anti-I2, anti-OmpC and ASCA as quantitative traits. METHODS: Expression of
      antibodies to microbial antigens was measured by enzyme-linked immunosorbant
      assay (ELISA) and a standard approximately 10 cM whole genome microsatellite
      study was conducted. Single nucleotide polymorphism genotyping was performed
      using either Illumina or TaqMan MGB technology. Nuclear factor Kappa B (NF
      kappaB) activation in cells from Epstein-Barr virus (EBV)-transformed cell lines
      was assessed using an electrophoretic mobility shift assay and protein was
      measured using ELISA and western blotting. RESULTS: Evidence for linkage to anti
      CBir1 expression was detected on human chromosome 4 (logarithm of odds (LOD) 1.82
      at 91 cM). We therefore directly proceeded to test the association of haplotypes
      in NFKB1, a candidate gene. One haplotype, H1, was associated with anti-CBir1 (p
      = 0.003) and another, H3, was associated with ASCA (p = 0.023). Using cell lines
      from Crohn's disease patients with either H1 or H3, NF-kappaB activation and NF
      kappaB p105 and p50 production were significantly lower for patients with H1
      compared to patients with H3. CONCLUSIONS: These results suggest that NFKB1
      haplotypes induce dysregulation of innate immune responses by altering NF-kappaB
      expression. The results also show the use of EBV-transformed lymphoblastoid cell
      lines to conduct phenotypic studies of genetic variation.

PMID- 18832527
TI  - Handedness effects on procedural training in pediatrics.
AB  - OBJECTIVE: To determine handedness effects on procedural training. PATIENTS AND
      METHODS: Pediatric trainees and attendings from 3 institutions participated in a
      Web-based survey examining whether handedness affected learning procedures, the
      hand used to perform procedures, and if handedness training was received. RESULTS
      AND CONCLUSIONS: Of 778 physicians, 39% completed surveys, and 11% wrote with
      their left hand. Learning procedures were affected in left-handed physicians (60%
      vs 7.7%; odds ratio [OR] = 17.9; 95% confidence interval [CI] = 7.9-40.1), and
      they used their non-dominant or both hands to perform procedures (48.6% vs 21%;
      OR = 3.6; 95% CI = 1.7-7.4). Few physicians received handedness training (20% vs
      10.7%; P= .16). Left-handed physicians were affected learning lumbar puncture
      (29% vs 4%; OR= 10.0; 95% CI = 3.8-26.4), intubation (36% vs 5%; OR=11.0; 95%
      CI=4.4-27.4), and suturing (32% vs 4%; OR = 11.7; 95% CI = 4.5-30.5).

PMID- 18832528
TI  - The effect of universal maternal screening on the incidence of neonatal early
      onset group B streptococcal disease.
AB  - OBJECTIVE: To determine the effect of the revised guidelines on incidence of
      neonatal early-onset group B streptococcal disease (EoGBS) via retrospective
      analysis of births in a military population. METHODS: Information from records of
      all live births within military hospitals from 1993 to 2007 was obtained. The
      data were divided into three time frames, representing the evolution of
      identifying and managing at-risk deliveries for GBS transmission. Incidence of
      EoGBS decreased from 1.95 to 0.72 per 1000 live births following institution of
      the 1996 Centers for Disease Control and Prevention recommendations and continued
      to fall to 0.47 per 1000 since the adoption of universal screening in 2002.
      CONCLUSIONS: Universal culture-based screening is more effective than risk-based
      screening in preventing EoGBS in term infants. Cases of EoGBS continue to occur,
      however, at a baseline rate of nearly 0.5 per 1000 births, thus emphasizing the
      need for rapid diagnostics and ultimately a vaccine.

PMID- 18832529
TI  - Malnutrition: a hidden problem in hospitalized children.

PMID- 18832530
TI  - Predictors of pediatric emergency patients discharged against medical advice.
AB  - Based on a retrospective 5-year medical record review, this study characterizes
      factors associated with patients discharged against medical advice (AMA) from a
      tertiary pediatric emergency department (ED) and compares rates of return to the
      ED and admission to the hospital with those of patients routinely discharged.
      Data from 94 patients discharged AMA are compared with those of 188 control
      patients. Pediatric patients at risk for discharge AMA are older than 15 years
      (odds ratio [OR], 3.561; 95% confidence interval [CI], 1.695-7.482), self
      register independent of a parent (OR, 3.100; 95% CI, 1.818-152.770), arrive by
      ambulance (OR, 2.761; 95% CI, 1.267-6.018), involve a consultant (OR, 2.592; 95%
      CI, 1.507-4.458), and have a chief complaint of abdominal pain (OR, 3.095; 95%
      CI, 1.154-8.303). Negative predictors include urgent triage (OR, 0.155; 95% CI,
      0.039-0.618), a chief complaint of upper respiratory tract illness or otitis
      media (OR, 0.229; 95% CI, 0.075-0.702), and discharge diagnoses of infection
      (adjusted OR, 0.053; 95% CI, 0.004-0.767), disease of the nervous system and
      sense organs (adjusted OR, 0.066; 95% CI, 0.005-0.898), respiratory illness
      (adjusted OR, 0.072; 95% CI, 0.007-0.718), and gastrointestinal disease (adjusted
      OR, 0.050; 95% CI, 0.006-0.419). Certain key elements of discharge AMA are well
      documented, including consequences of discharge AMA (74.5%) and instructions for
      care (54.3%). Other elements such as alternative therapies (1.1%) are poorly
      documented. Patients discharged AMA have a significantly higher return rate
      (24.5%) within 15 days compared with patients who have routine discharge (6.4%)
      (chi2=18.85, P<.001). Ninety-six percent of patients who return to the ED have
      the same chief complaint at both visits if discharged AMA compared with 50% of
      patients who are discharged routinely (P=.003), with 25% admission rates at the
      time of second visit for both types of discharges. Adolescents who register
      themselves are at increased risk for discharge AMA. Patients who are triaged as
      urgent or nonurgent or who have minor illnesses are likely to be dispositioned
      routinely. Patients discharged AMA are more likely to return to the ED with the
      same complaint than patients who are routinely discharged.

PMID- 18832531
TI  - Epidemiologic findings of cancer detected in a pediatric emergency department.
AB  - This study describes epidemiologic findings of pediatric cancer diagnosed in the
      emergency department (ED) setting. Medical records are retrospectively reviewed
      on all patients in the hospital's cancer database between 2000 and 2004 who were
      diagnosed as having cancer or whose oncologic diagnosis was missed during their
      ED presentation. Of 427 patients identified in the cancer database, 18% (77 of
      427) are analyzed. Oncologic diagnosis was missed in 5% (4 of 77) of the eligible
      patients initially presenting to the ED. The incidence of cancer in the ED is
      22.8 cases per 100,000 ED visits. The most prevalent cancer is related to the
      hematologic system (37.7%), followed by the central nervous system (31.2%) and
      the abdomen (22.1%). Hematologic, central nervous system, and abdominal cancers
      constitute approximately 90% of all childhood cancers. Cancer is diagnosed
      frequently in our ED patient population. Based on the prevalence of certain
      tumors, the diagnostic approach to children with hematologic, neurologic, or
      abdominal complaints should include evaluation for any underlying cancer.

PMID- 18832532
TI  - Clinical response to 2 commonly used switch formulas occurs within 1 day.
AB  - Very fussy or extremely fussy infants were randomized to receive: soy-based
      formula (Soy: n = 82) or a partially hydrolyzed cow's milk protein (CMP), low
      lactose formula (PHF: n = 77) in a multicenter, double-blind, randomized,
      parallel, prospective 28-day feeding trial. Body weight and infant formula
      tolerance were reported. Adverse events were recorded throughout the study. A
      significant reduction in mean scores of fussiness, gas, spit-up, and crying
      compared with baseline measures was observed in infants who received either Soy
      or PHF within 1 day of formula intake; improvement in symptoms was sustained by
      study end. Stool consistency remained constant through day 28 in the PHF group,
      whereas stools in the Soy group became more firm by day 2 and did not return to
      prestudy consistency. PHF, with a protein profile patterned more closely on human
      breast milk, improved symptoms of formula intolerance as well as soy-based
      formula.

PMID- 18832533
TI  - Mental status changes and bradycardia: don't forget the eye! Traumatic hyphema
      can mimic increased intracranial pressure.

PMID- 18832534
TI  - Mammalian bites.

PMID- 18832535
TI  - Age- and ethnic-specific elevation of ALT among obese children at risk for
      nonalcoholic steatohepatitis (NASH): implications for screening.
AB  - The objectives are to: (1) characterize ethnic-specific differences in alanine
      aminotransferase (ALT) elevation among obese children, (2) investigate the
      earliest ages at which significant ALT elevation occurs, and (3) determine
      associations between ALT and biochemical parameters. A cohort of 134 multiethnic
      obese children and adolescents was analyzed retrospectively. ALT levels > or =45
      U/L or <45 U/L, denoting high or normal risk, were used to categorize obese
      children's risk for developing nonalcoholic steatohepatitis. In all, 60% of
      Hispanics had high-risk ALT levels compared with 12% of whites and 8% of blacks.
      A significantly higher proportion of boys had ALT > or = 45 U/L (49.4%, vs 37.9%
      for girls, P = .002); 17.5% were Hispanic boys less than 7 years old. Obese
      Hispanic children, particularly boys, not only have higher ALT levels but present
      alarmingly young with high-risk levels. This study highlights a discrete subgroup
      of children who may present with fatty liver at a younger age and should be
      screened earlier.

PMID- 18832536
TI  - A 3 1/2-year-old child with bilateral lower extremity pain of 3 weeks duration.

PMID- 18832537
TI  - Management of infantile colic: a review.
AB  - Infantile colic is an easily identified childhood entity that has no clear
      treatment guidelines. The management of infantile colic varies among physicians,
      and families are often frustrated by the medical community's inability to
      prescribe a cure for colic. This article reviews the current concepts for
      management options of infantile colic.

PMID- 18832538
TI  - An infant with erythroderma, skin scaling, chronic emesis, and intractable
      diarrhea.

PMID- 18832539
TI  - Hypokalemia and nocturia in a 15-year-old girl.

PMID- 18832540
TI  - Long-term outcomes of physician peer teaching.
AB  - Research conducted in 10 cities assessed long-term pediatric asthma outcomes from
      a peer teaching intervention for physicians to improve their asthma-related
      clinical and counseling skills. Hypotheses were better outcomes for patients,
      symptom reduction, less health care use, and enhanced view of the physician.
      Peers trained 53 intervention group pediatricians (seeing 418 patients); 48
      pediatricians (seeing 452 patients) were controls. Patients provided baseline and
      2-year follow-up data, collected by telephone interview and from medical records.
      Intent-to-treat analyses used Poisson regression and general estimation
      equations. Treatment physicians' patients gave them higher performance ratings (
      P = .02). Patients had fewer sleep disruptions from asthma symptoms ( P = .03).
      Those with baseline health care use had fewer ED visits ( P = .005),
      hospitalizations (P = .03), and urgent office visits (P = .001), and they made
      fewer phone calls to the doctor's office (P = .02). Treatment physicians spent no
      more patient visit time than control physicians. Peer training increased
      patient's positive views of clinician's performance and reduced children's
      symptoms and health care use up to two years post program.

PMID- 18832541
TI  - Cleidocranial dysplasia: report of 3 cases and literature review.
AB  - BACKGROUND: Cleidocranial dysplasia (CCD) is an autosomal-dominant skeletal
      dysplasia syndrome that is characterized by widely patent calvarial sutures,
      clavicular hypoplasia, supernumerary teeth, and short stature. It is caused by
      mutations of the transcription factor RUNX2, which is known as a major regulator
      of bone differentiation. OBJECTIVE: To report on 3 Chinese pediatric cases of CCD
      with an emphasis on the clinical presentation and diagnostic modalities. CASE
      SUMMARY: 3 Chinese children were admitted to our hospital because of short
      stature. All the children had hypoplastic clavicles, absent calvarium, open
      fontanel, and messy palmprint. Screening laboratory test results for bone mineral
      density, free thyroxine, and thyroid stimulating hormone were all normal. One
      child had mental retardation. Two were hereditary, and 1 was sporadic.
      CONCLUSION: These results showed that CCD should be suspected in patients with
      short stature and poor clavicles, calvarium, or teeth. Timely recognition and
      hereditary tendency counseling is required and useful.

PMID- 18832542
TI  - Preseason neuromuscular exercise program reduces sports-related knee pain in
      female adolescent athletes.

PMID- 18832543
TI  - Vomiting in a girl with autism.

PMID- 18832544
TI  - Shwachman-Diamond syndrome presenting as hypoglycemia.

PMID- 18832545
TI  - An unusual cause of acute polyarticular arthritis.

PMID- 18832546
TI  - Refractory pneumonia in a Mexican American infant.

PMID- 18832547
TI  - Outcome of functional constipation in childhood: a 10-year follow-up study.
AB  - OBJECTIVES: To assess the outcome of patients presenting with functional
      constipation in childhood during a 10-year period and to determine any risk
      factors for developing persistent constipation throughout adolescence and
      adulthood. PATIENTS AND METHODS: 72 children (mean age 4 years; 40 boys) referred
      for constipation were included in a longitudinal set of observations. Initial
      workup included segmental colonic transit time and anorectal manometry; 45 of the
      72 patients could be reevaluated 10 to 12 years later. RESULTS: 21 of 45 patients
      (46%; 95% confidence interval 29% to 67%) remained constipated at follow-up.
      Encopresis and recurrent abdominal pain were present in 25% and 56% of patients,
      respectively. Patients with anorectal dyssynergia remained more frequently
      constipated at follow-up than the others: 61% versus 29% (P < .05). CONCLUSION:
      Almost 50% of patients presenting with constipation during childhood remained
      constipated on long-term follow-up. Anorectal dyssynergia is associated with a
      worse prognosis.

PMID- 18832548
TI  - A child with recurrent episodes of fever and joint pain.

PMID- 18832549
TI  - Short-term outcomes of late preterms: an institutional experience.
AB  - This article describes the short-term outcomes of late preterm neonates born
      between 34 and 36 (6/7) weeks gestational age (GA) in a 4-year period. A total of
      1381/ 20554 (6.7%) births were between 34 and 36 weeks of GA and were
      predominantly Caucasian (87%). In all, 697/1381 (51%) were admitted to nursery
      whereas 684/1381 (49%) remained with their mothers. Of the babies born at 34, 35,
      and 36 weeks GA, 97%, 53%, and 32%, respectively, required admission and of these
      30%, 33%, and 23%, respectively, required respiratory support. Air leaks
      developed in <4% infants. Median length of stay and age at full enteral feeds
      were 11, 6, and 4 days and 10, 6, and 3 days for 34, 35, and 36 weeks GA,
      respectively. It is concluded that late preterms have significant morbidity in
      the neonatal period.

PMID- 18832550
TI  - Evaluation of microcytic anemia.
AB  - Anemia is defined as a reduction in red blood cell mass or hemoglobin
      concentration in blood. It is statistically differentiated from normal states as
      a hemoglobin concentration or hematocrit 2 SD below the mean for the healthy
      population adjusted for age and sex. Anemias may be classified based on the
      morphologic function of red blood cells and their size on a peripheral blood
      smear. Subcategories are microcytic, normocytic, and macrocytic anemias, but
      these are not mutually exclusive. In infants and children, the most common form
      of anemia is microcytic. A detailed history and physical examination with
      appropriate laboratory test results can help detect the correct cause of anemia
      in most patients. The objective of this article is to aid physicians taking care
      of children in conducting a proper evaluation to identify the correct cause of
      microcytic anemia.

PMID- 18832551
TI  - Evaluation and treatment of hypertension in general pediatric practice.
AB  - Hypertension (HTN) in children and adolescents has become increasingly common. We
      sought to identify variability in the approach to HTN among general pediatricians
      as well as obstacles to care of hypertensive youth by surveying pediatricians
      referring to an urban children's hospital. Although most pediatricians begin
      blood pressure measurement at 3 years, there was substantial variability in the
      initial diagnostic evaluation of hypertensive patients. Just 7% of pediatricians
      routinely start antihypertensive drug treatment for HTN, whereas 82% refer their
      hypertensive patients to a specialist; 40% of pediatricians felt uncomfortable
      evaluating and treating HTN. Pediatricians unfamiliar with The Fourth Report were
      more likely to be uncomfortable with the care of hypertensive patients than those
      familiar with it (54% vs 33%, P < .05). Current practice does not appear to
      follow recent consensus recommendations. Interventions designed to address the
      issues identified in this survey may lead to improved care for pediatric patients
      with HTN.

PMID- 18832552
TI  - Screening for mesothelioma: more harm than good?

PMID- 18832553
TI  - Stress in the ER (endoplasmic reticulum): a matter of life and death for
      epithelial cells.

PMID- 18832554
TI  - Gefitinib first or gefitinib second: is timing everything in the treatment of
      EGFR mutant non-small cell lung cancer?

PMID- 18832555
TI  - Matters of the heart: the brain in pediatric sleep apnea.

PMID- 18832556
TI  - Epigenetic studies should focus on specific cell types.

PMID- 18832557
TI  - Blood pressure after adenotonsillectomy in children with obstructive sleep
      disordered breathing.

PMID- 18832558
TI  - What can the NHANES data tell us about the tuberculin skin test and the risk for
      active tuberculosis?

PMID- 18832559
TI  - The neural correlates of reward-related trial-and-error learning: an fMRI study
      with a probabilistic learning task.
AB  - This fMRI study investigated the neural correlates of reward-related trial-and
      error learning in association with changing degrees of stimulus-outcome
      predictabilities. We found that decreasing predictability was associated with
      increasing activation in a frontoparietal network. Only maximum predictability
      was associated with signal decreases across the learning process. The receipt of
      monetary reward revealed activation in the striatum and associated frontoparietal
      regions. Present data indicate that during reward-related learning, high
      uncertainty forces areas relevant for cognitive control to remain activated. In
      contrast, learning on the basis of predictable stimulus-outcome associations
      enables the brain to reduce resources in association with the processes of
      prediction.

PMID- 18832560
TI  - Age-related declines in general cognitive abilities of Balb/C mice are associated
      with disparities in working memory, body weight, and general activity.
AB  - A defining characteristic of age-related cognitive decline is a deficit in
      general cognitive performance. Here we use a testing and analysis regimen that
      allows us to characterize the general learning abilities of young (3-5 mo old)
      and aged (19-21 mo old) male and female Balb/C mice. Animals' performance was
      assessed on a battery of seven diverse learning tasks. Aged animals exhibited
      deficits in five of the seven tasks and ranked significantly lower than their
      young counterparts in general learning abilities (aggregate performance across
      the battery of tasks). Aging added variability to common core performance (i.e.,
      general learning ability), which translated into increased variability on the
      individual cognitive tasks. Relatedly, general learning abilities did not differ
      between the two ages among the best quartile of learners (i.e., cognitive
      abilities were spared in a subsample of the aged animals). Additionally, working
      memory capacity (resistance to interference) and duration (resistance to decay)
      accounted for significantly more of the variability in general learning abilities
      in aged relative to young animals. Tests of 15 noncognitive performance variables
      indicated that an increase in body weight (and an associated decrease in general
      activity) was characteristic of those aged animals which exhibited deficient
      general learning abilities. These results suggest the possibility that general
      cognitive deficits in aged animals reflect a failure of specific components of
      the working memory system, and may be related to variations in body weight and an
      associated decrease in activity.

PMID- 18832561
TI  - De novo mRNA synthesis is required for both consolidation and reconsolidation of
      fear memories in the amygdala.
AB  - Memory consolidation is the process by which newly learned information is
      stabilized into long-term memory (LTM). Considerable evidence indicates that
      retrieval of a consolidated memory returns it to a labile state that requires it
      to be restabilized. Consolidation of new fear memories has been shown to require
      de novo RNA and protein synthesis in the lateral nucleus of the amygdala (LA). We
      have previously shown that de novo protein synthesis in the LA is required for
      reconsolidation of auditory fear memories. One key question is whether protein
      synthesis during reconsolidation depends on already existing mRNAs or on
      synthesis of new mRNAs in the amygdala. In the present study, we examined the
      effect of mRNA synthesis inhibition during consolidation and reconsolidation of
      auditory fear memories. We first show that intra-LA infusion of two different
      mRNA inhibitors dose-dependently impairs long-term memory but leaves short-term
      memory (STM) intact. Next, we show that intra-LA infusion of the same inhibitors
      dose-dependently blocks post-reactivation long-term memory (PR-LTM), whereas post
      reactivation short-term memory (PR-STM) is left intact. Furthermore, the same
      treatment in the absence of memory reactivation has no effect. Together, these
      results show that both consolidation and reconsolidation of auditory fear
      memories require de novo mRNA synthesis and are equally sensitive to disruption
      of de novo mRNA synthesis in the LA.

PMID- 18832562
TI  - Persistent ERK activation maintains learning-induced long-lasting modulation of
      synaptic connectivity.
AB  - Pyramidal neurons in the piriform cortex from olfactory-discrimination (OD)
      trained rats undergo synaptic modifications that last for days after learning. A
      particularly intriguing modification is reduced paired-pulse facilitation (PPF)
      in the synapses interconnecting these cells; a phenomenon thought to reflect
      enhanced synaptic release. The molecular machinery underlying this prolonged
      physiological modulation of synaptic connectivity is yet to be described. We have
      recently shown that extracellular regulated kinase (ERK) pathway and protein
      kinase C (PKC) are also required for learning-induced enhancement of intrinsic
      neuronal excitability. Here we examine whether these signal-transduction cascades
      are instrumental for the learning-induced, long-lasting PPF reduction. Days after
      learning completion, PD98059, a selective inhibitor of MEK, the upstream kinase
      of ERK, increased PPF in neurons from trained, but not in neurons from naive and
      pseudo-trained rats. Consequently, the differences in PPF between neurons from
      trained rats and controls were abolished. The level of activated ERK in
      synaptoneurosomes was significantly higher in piriform cortex samples prepared
      from trained rats. Notably, ERK activation revealed that PPF reduction lags
      behind ERK activation by 2 d. Similarly, the PKC blocker, GF-109203X, enhanced
      PPF in neurons from trained rats only, thus abolishing the differences between
      groups. Interestingly, the PKC activator, OAG, had no effect, indicating that PKC
      activation is required, but not sufficient for long-lasting PPF reduction. Our
      data show that persistent ERK activation has a key role in maintaining learning
      induced PPF reduction for days. This time frame of compartmental ERK-dependent
      synaptic modulation suggests a novel role for ERK in cortical function.

PMID- 18832563
TI  - Role of the phosphoinositide 3-kinase-Akt-mammalian target of the rapamycin
      signaling pathway in long-term potentiation and trace fear conditioning memory in
      rat medial prefrontal cortex.
AB  - Phosphatidylinositol 3-kinase (PI3K) and its downstream targets, including Akt
      (also known as protein kinase B, PKB), mammalian target of rapamycin (mTOR), the
      70-kDa ribosomal S6 kinase (p70S6k), and the eukaryotic initiation factor 4E
      (eIF4E)-binding protein 1 (4E-BP1), may play important roles in long-term
      synaptic plasticity and memory in many brain regions, such as the hippocampus and
      the amygdala. The present study investigated the role of the PI3K/Akt-mTOR
      signaling pathway in the medial prefrontal cortex (mPFC), also a crucial neural
      locus for the control of cognition and emotion. Western blot analysis of mPFC
      tissues showed an activation of phosphorylation of Akt at the Ser473 residues,
      mTOR, p70S6k, and 4E-BP1 in response to long-term potentiation (LTP)-inducing
      high-frequency stimulation (HFS). Infusion of PI3K inhibitors (wortmannin and
      LY294002) and an mTOR inhibitor (rapamycin) into the mPFC in vivo suppressed HFS
      induced LTP as well as the phosphorylation of PI3K/Akt-mTOR signaling pathway. In
      parallel, these inhibitors interfered with the long-term retention of trace fear
      memory examined 3 d and 6 d after the trace fear conditioning training, whereas
      short-term trace fear memory and object recognition memory were kept intact.
      These results provide evidence of involvement of activation of the PI3K/Akt-mTOR
      signaling pathway in the mPFC for LTP and long-term retention of trace fear
      memory.

PMID- 18832564
TI  - Fear relevancy, strategy use, and probabilistic learning of cue-outcome
      associations.
AB  - The goal of this study was to determine how the fear relevancy of outcomes during
      probabilistic classification learning affects behavior and strategy use. Novel
      variants of the "weather prediction" task were created, in which cue cards
      predicted either looming fearful or neutral outcomes in a between-groups design.
      Strategy use was examined by goodness-of-fit estimates of response patterns
      across trial blocks to mathematical models of simple, complex, and
      nonidentifiable strategies. Participants in the emotional condition who were
      fearful of the outcomes had greater skin conductance responses compared with
      controls and performed worse, used suboptimal strategies, and had less insight
      into the predictive cue features during initial learning. In contrast, nonfearful
      participants in the emotional condition used more optimal strategies than the
      other groups by the end of the two training days. Results have implications for
      understanding how individual differences in fear relevancy alter the impact of
      emotion on feedback-based learning.

PMID- 18832565
TI  - A limited role for the hippocampus in the modulation of novel-object preference
      by contextual cues.
AB  - Recent evidence suggests that rats require an intact hippocampus in order to
      recognize familiar objects when they encounter them again in a different context.
      The two experiments reported here further examined how changes in context affect
      rats' performance on the novel-object preference (NOP) test of object-recognition
      memory, and how those effects interact with the effects of HPC damage. Rats with
      HPC lesions and control rats received NOP testing in either the same context in
      which they had previously encountered sample objects, or in a different but
      equally familiar context. In Experiment 1, the two contexts had very few
      overlapping cues within or outside the apparatus; thus, the differences between
      them were global. Consistent with previous results, control rats showed a novel
      object preference in both the unchanged and (globally) changed contexts, whereas
      rats with HPC lesions displayed a preference only in the unchanged context. In
      Experiment 2, the context shift included only local features proximal to the test
      objects. The main results were the reverse of Experiment 1--rats with HPC lesions
      displayed a novel-object preference in both the unchanged and (locally) changed
      contexts, whereas control rats displayed a preference only in the unchanged
      context. The findings are consistent with the view that HPC damage does not cause
      a general inability to recognize objects, nor an inability to encode or store a
      representation of the context in which the objects are encountered. They suggest
      instead that HPC damage impairs the ability to remember specific locations of
      familiar objects within a particular context.

PMID- 18832566
TI  - The NO-cGMP-PKG signaling pathway regulates synaptic plasticity and fear memory
      consolidation in the lateral amygdala via activation of ERK/MAP kinase.
AB  - Recent studies have shown that nitric oxide (NO) signaling plays a crucial role
      in memory consolidation of Pavlovian fear conditioning and in synaptic plasticity
      in the lateral amygdala (LA). In the present experiments, we examined the role of
      the cGMP-dependent protein kinase (PKG), a downstream effector of NO, in fear
      memory consolidation and long-term potentiation (LTP) at thalamic and cortical
      input pathways to the LA. In behavioral experiments, rats given intra-LA
      infusions of either the PKG inhibitor Rp-8-Br-PET-cGMPS or the PKG activator 8-Br
      cGMP exhibited dose-dependent impairments or enhancements of fear memory
      consolidation, respectively. In slice electrophysiology experiments, bath
      application of Rp-8-Br-PET-cGMPS or the guanylyl cyclase inhibitor LY83583
      impaired LTP at thalamic, but not cortical inputs to the LA, while bath
      application of 8-Br-cGMP or the guanylyl cyclase activator YC-1 resulted in
      enhanced LTP at thalamic inputs to the LA. Interestingly, YC-1-induced
      enhancement of LTP in the LA was reversed by concurrent application of the MEK
      inhibitor U0126, suggesting that the NO-cGMP-PKG signaling pathway may promote
      synaptic plasticity and fear memory formation in the LA, in part by activating
      the ERK/MAPK signaling cascade. As a test of this hypothesis, we next showed that
      rats given intra-LA infusion of the PKG inhibitor Rp-8-Br-PET-cGMPS or the PKG
      activator 8-Br-cGMP exhibit impaired or enhanced activation, respectively, of
      ERK/MAPK in the LA after fear conditioning. Collectively, our findings suggest
      that an NO-cGMP-PKG-dependent form of synaptic plasticity at thalamic input
      synapses to the LA may underlie memory consolidation of Pavlovian fear
      conditioning, in part, via activation of the ERK/MAPK signaling cascade.

PMID- 18832567
TI  - Overexpression of mIGF-1 in keratinocytes improves wound healing and accelerates
      hair follicle formation and cycling in mice.
AB  - Insulin-like growth factor 1 (IGF-1) is an important regulator of growth,
      survival, and differentiation in many tissues. It is produced in several isoforms
      that differ in their N-terminal signal peptide and C-terminal extension peptide.
      The locally acting isoform of IGF-1 (mIGF-1) was previously shown to enhance the
      regeneration of both muscle and heart. In this study, we tested the therapeutic
      potential of mIGF-1 in the skin by generating a transgenic mouse model in which
      mIGF-1 expression is driven by the keratin 14 promoter. IGF-1 levels were
      unchanged in the sera of hemizygous K14/mIGF-1 transgenic animals whose growth
      was unaffected. A skin analysis of young animals revealed normal architecture and
      thickness as well as proper expression of differentiation and proliferation
      markers. No malignant tumors were formed. Normal homeostasis of the putative stem
      cell compartment was also maintained. Healing of full-thickness excisional wounds
      was accelerated because of increased proliferation and migration of
      keratinocytes, whereas inflammation, granulation tissue formation, and scarring
      were not obviously affected. In addition, mIGF-1 promoted late hair follicle
      morphogenesis and cycling. To our knowledge, this is the first work to
      characterize the simultaneous, stimulatory effect of IGF-1 delivery to
      keratinocytes on two types of regeneration processes within a single mouse model.
      Our analysis supports the use of mIGF-1 for skin and hair regeneration and
      describes a potential cell type-restricted action.

PMID- 18832568
TI  - Up-regulation of activating transcription factor-5 suppresses SAP expression to
      activate T cells in hemophagocytic syndrome associated with Epstein-Barr virus
      infection and immune disorders.
AB  - Hemophagocytic syndrome (HPS) is a fatal, pro-inflammatory cytokine disorder that
      is associated with viral infections and immune disorders. Previously, we
      demonstrated that Epstein-Barr virus latent membrane protein-1 (LMP-1) could down
      regulate the SAP gene, enhancing Th1 cytokine secretion in T cells and leading to
      HPS. The exact mechanism of SAP gene regulation by LMP-1 remains to be clarified.
      In this study, using cDNA microarray analysis, we identified ATF5 as the
      candidate transcriptional repressor for SAP expression in LMP-1-expressing T
      cells. LMP-1 up-regulated ATF5 via TRAF2,5/NF-kappaB signals to suppress SAP gene
      expression. Reporter assays and electrophoretic mobility shift assays revealed
      that ATF5 bound differentially to two sites of the SAP promoter. In resting T
      cells, ATF5 bound predominantly to the high-affinity site in the -81 to -74
      region while additionally binding to the low-affinity site at -305 to -296 in LMP
      1-expressing T cells. Such binding subsequently disrupted the transcription of
      the SAP gene. At the same time, Th1 cytokine secretion was enhanced. This
      phenomenon was also observed in conditions such as ATF5 overexpression,
      phytohemagglutinin stimulation of primary T cells, and ligand engagement of T
      cell lines. Therefore, the down-regulation of the SAP gene by ATF5 may represent
      a common mechanism for the pathogenesis of HPS that is associated with either
      Epstein-Barr virus infection or immune disorders with dysregulated T-cell
      activation.

PMID- 18832569
TI  - Keratinocyte expression of MMP3 enhances differentiation and prevents tumor
      establishment.
AB  - Matrix metalloproteinase (MMP)-3 is induced by multiple cell types in the skin
      during processes involved in both normal and pathological tissue remodeling. We
      previously demonstrated that MMP3-null animals have an increased sensitivity to
      the development of squamous cell carcinoma, suggesting that overall, MMP3 has a
      protective role in squamous cell carcinoma. However, not all cellular responses
      affected by a loss of MMP3 are tumor-protective, and tumor expression of MMP3 is
      co-incident with an invasive tumor phenotype. Transgenic mice were generated with
      MMP3 targeted to keratinocytes to examine the biological role of tumor-produced
      MMP3. Overexpression of MMP3 reduced tumor multiplicity in response to chemically
      induced squamous cell carcinoma. Vascular density was increased with MMP3
      overexpression; however, other cellular processes, including tumor growth and
      leukocyte infiltration, were unaffected. In accordance with the change in tumor
      multiplicity, SP-1 murine papilloma cell lines that were generated to stably
      express MMP3 lost the capacity to establish palpable tumors following orthotopic
      injection into immunocompromised mice. Analysis of epidermal biopsies taken at 1
      to 2 weeks postinjection revealed that these MMP3-expressing Sp-1 lines had
      reduced levels of proliferation and pronounced differentiation. These same cells
      demonstrated an increased ability to differentiate in vitro, an effect that was
      inhibited by broad-spectrum MMP and selective MMP3 inhibition. These studies
      suggest that keratinocyte expression of MMP3 promotes cellular differentiation,
      impeding tumor establishment during tumorigenesis.

PMID- 18832570
TI  - Adenoviral overexpression and small interfering RNA suppression demonstrate that
      plasminogen activator inhibitor-1 produces elevated collagen accumulation in
      normal and keloid fibroblasts.
AB  - Keloids are tumor-like skin scars that grow as a result of the aberrant healing
      of skin injuries, with no effective treatment. We provide new evidence that both
      overexpression of plasminogen activator inhibitor-1 (PAI-1) and elevated collagen
      accumulation are intrinsic features of keloid fibroblasts and that these
      characteristics are causally linked. Using seven strains each of early passage
      normal and keloid fibroblasts, the keloid strains exhibited inherently elevated
      collagen accumulation and PAI-1 expression in serum-free, 0.1% ITS+ culture;
      larger increases in these parameters occurred when cells were cultured in 3%
      serum. To demonstrate a causal relationship between PAI-1 overexpression and
      collagen accumulation, normal fibroblasts were infected with PAI-1-expressing
      adenovirus. Such cells exhibited a two- to fourfold increase in the accumulation
      of newly synthesized collagen in a viral dose-dependent fashion in both
      monolayers and fibrin gel, provisional matrix-like cultures. Three different PAI
      1-targeted small interfering RNAs, alone or in combination, produced greater than
      an 80% PAI-1 knockdown and reduced collagen accumulation in PAI-1-overexpressing
      normal or keloid fibroblasts. A vitronectin-binding mutant of PAI-1 was
      equipotent with wild-type PAI-1 in inducing collagen accumulation, whereas a
      complete protease inhibitor mutant retained approximately 50% activity. Thus, PAI
      1 may use more than its protease inhibitory activity to control keloid collagen
      accumulation. PAI-1-targeted interventions, such as small interfering RNA and
      lentiviral short hairpin RNA-containing microRNA sequence suppression reported
      here, may have therapeutic utility in the prevention of keloid scarring.

PMID- 18832571
TI  - Specific mutations in the beta-catenin gene (CTNNB1) correlate with local
      recurrence in sporadic desmoid tumors.
AB  - Desmoid fibromatosis is a rare, nonmetastatic neoplasm marked by local
      invasiveness and relentless recurrence. Molecular determinants of desmoid
      recurrence remain obscure. beta-Catenin deregulation has been commonly identified
      in sporadic desmoids although the incidence of CTNNB1 (the gene encoding beta
      catenin) mutations is uncertain. Consequently, we evaluated the prevalence of
      CTNNB1 mutations in a large cohort of sporadic desmoids and examined whether
      mutation type was relevant to desmoid outcome. Desmoid specimens (195 tumors from
      160 patients, 1985 to 2005) and control dermal scars were assembled into a
      clinical data-linked tissue microarray. CTNNB1 genotyping was performed on a 138
      sporadic desmoid subset. Immunohistochemical scoring was performed per standard
      criteria and data were analyzed using Kaplan-Meier and other indicated methods.
      CTNNB1 mutations were observed in 117 of 138 (85%) of desmoids. Three discrete
      mutations in two codons of CTNNB1 exon 3 were identified: 41A (59%), 45F (33%),
      and 45P (8%, excluded from further analysis because of rarity). Five-year
      recurrence-free survival was significantly poorer in 45F-mutated desmoids (23%, P
      < 0.0001) versus either 41A (57%) or nonmutated tumors (65%). Nuclear beta
      catenin expression was observed in 98% of specimens and intensity was inversely
      correlated with incidence of desmoid recurrence (P < 0.01). In conclusion, CTNNB1
      mutations are highly common in desmoid tumors. Furthermore, patients harboring
      CTNNB1 (45F) mutations are at particular risk for recurrence and therefore may
      especially benefit from adjuvant therapeutic approaches.

PMID- 18832572
TI  - Tolerance to melanin-associated antigen in autoimmune uveitis is mediated by
      CD4+CD25+ T-regulatory cells.
AB  - Experimental autoimmune anterior uveitis (EAAU) serves as an animal model for
      human idiopathic AU, the most common form of intraocular inflammation of
      significant morbidity whose recurrence can lead to permanent vision loss. This
      study was undertaken to inhibit EAAU by inducing tolerance to melanin-associated
      antigen (MAA) and to investigate the underlying mechanisms responsible for
      tolerance induction. Intravenous administration of MAA both induced tolerance and
      inhibited EAAU in Lewis rats. Flow cytometric analysis revealed that the
      proliferation of lymph node cells in response to antigenic stimulation was
      drastically reduced in the state of tolerance both in vivo and in vitro. Our
      results from co-culture experiments demonstrated that intravenous administration
      of MAA led to the generation of T-regulatory cells that suppress T-cell
      proliferative responses and induce tolerance. Expression levels of both
      interleukin-10 and transforming growth factor-beta2 were elevated whereas reduced
      levels of tumor necrosis factor-alpha, interferon-gamma, and interleukin-2 were
      detected in tolerance-induced animals. Tolerance was reversed by replenishing
      these animals with recombinant interleukin-2. Tolerance could be adoptively
      transferred by removing lymph node cells from tolerance-induced donors and giving
      them to recipient rats. Interestingly, adoptive transfer of tolerance failed when
      lymph nodes cells were depleted of CD4(+)CD25(+) T cells. In conclusion, T-cell
      nonresponsiveness because of active suppression mediated by T-regulatory cells
      facilitates the development of tolerance to MAA in EAAU.

PMID- 18832573
TI  - Regulation of the atheroma-enriched protein, SPRR3, in vascular smooth muscle
      cells through cyclic strain is dependent on integrin alpha1beta1/collagen
      interaction.
AB  - Atherosclerotic plaques express high levels of small proline-rich repeat protein
      (SPRR3), a previously characterized component of the cornified cell envelope of
      stratified epithelia, where it is believed to play a role in cellular adaptation
      to biomechanical stress. We investigated the physiological signals and underlying
      mechanism(s) that regulate atheroma-enriched SPRR3 expression in vascular smooth
      muscle cells (VSMCs). We showed that SPRR3 is expressed by VSMCs in both human
      and mouse atheromas. In cultured arterial VSMCs, mechanical cyclic strain, but
      neither shear stress nor lipid loading induced SPRR3 expression. Furthermore,
      this upregulation of SPRR3 expression was dependent on VSMC adherence to type I
      collagen. To link the mechanoregulation of SPRR3 to specific collagen/integrin
      interactions, we used blocking antibodies against either integrin alpha1 or
      alpha2 subunits and VSMCs from mice that lack specific collagen receptors. Our
      results showed a dependence on the alpha1beta1 integrin for SPRR3 expression
      induced by cyclic strain. Furthermore, we showed that integrin alpha1 but not
      alpha2 subunits were expressed on VSMCs within mouse lesions but not in normal
      arteries. Therefore, we identified the enrichment of the mechanical strain
      regulated protein SPRR3 in VSMCs of both human and mouse atherosclerotic lesions
      whose expression is dependent on the collagen-binding integrin alpha1beta1 on
      VSMCs. These data suggest that SPRR3 may play a role in VSMC adaptation to local
      biomechanical stress within the plaque microenvironment.

PMID- 18832574
TI  - A mutation in Rab38 small GTPase causes abnormal lung surfactant homeostasis and
      aberrant alveolar structure in mice.
AB  - The chocolate mutation, which is associated with oculocutaneous albinism in mice,
      has been attributed to a G146T transversion in the conserved GTP/GDP-interacting
      domain of Rab38, a small GTPase that regulates intracellular vesicular
      trafficking. Rab38 displays a unique tissue-specific expression pattern with
      highest levels present in the lung. The purpose of this study was to characterize
      the effects of Rab38-G146T on lung phenotype and to investigate the molecular
      basis of the mutant gene product (Rab38(cht) protein). Chocolate lungs exhibited
      a uniform enlargement of the distal airspaces with mild alveolar destruction as
      well as a slight increase in lung compliance. Alveolar type II cells were
      engorged with lamellar bodies of increased size and number. Hydrophobic
      surfactant constituents (ie, phosphatidylcholine and surfactant protein B) were
      increased in lung tissues but decreased in alveolar spaces, consistent with a
      malfunction in lamellar body secretion and the subsequent cellular accumulation
      of these organelles. In contrast to wild-type Rab38, native Rab38(cht) proteins
      were found to be hydrophilic and not bound to intracellular membranes.
      Unexpectedly, recombinant Rab38(cht) proteins retained GTP-binding activity but
      failed to undergo prenyl modification that is required for membrane-binding
      activity. These results suggest that the genetic abnormality of Rab38 affects
      multiple lysosome-related organelles, resulting in lung disease in addition to
      oculocutaneous albinism.

PMID- 18832575
TI  - Lipid droplet-associated proteins protect renal tubular cells from fatty acid
      induced apoptosis.
AB  - Proteinuria is a major cause of tubulointerstitial kidney damage, and free fatty
      acids bound to albumin are thought to play an important role in its pathogenesis.
      However, the mechanism whereby proteinuria causes tubulointerstitial damage to
      the kidney is unclear. Using primary human renal proximal tubular cells, we
      observed that albumin replete with fatty acids (rBSA) and defatted albumin (dBSA)
      complexed with linoleic acid (LA) induced significantly more apoptosis than did
      defatted albumin alone. Oxidative stress was partially involved in apoptotic
      induction by LA/dBSA but not by rBSA. Administration of fatty acid-bound BSA
      increased the number of lipid droplets (LDs) and the LD-associated proteins,
      adipocyte differentiation-related protein and TIP47. LDs are organelles that
      store esterified fatty acids, and the LD-associated proteins are presumed to
      facilitate LD formation. Knockdown of adipocyte differentiation-related protein
      or TIP47 by RNA interference enhanced induction of apoptosis by both rBSA and
      LA/dBSA. Apoptotic induction was observed similarly when either rBSA or LA/dBSA
      was applied to only the apical surfaces of polarized LLC-PK1 cells. The present
      results suggest that LDs and LD-associated proteins have protective effects
      against apoptosis induced by fatty acid-bound albumin by sequestering free fatty
      acids. Therapeutic manipulation of these LD-associated proteins could aid in the
      amelioration of nephritic diseases.

PMID- 18832576
TI  - Dysferlin deficiency shows compensatory induction of Rab27A/Slp2a that may
      contribute to inflammatory onset.
AB  - Mutations in the dysferlin gene cause limb girdle muscular dystrophy 2B (LGMD2B)
      and Miyoshi myopathy. Dysferlin-deficient cells show abnormalities in vesicular
      traffic and membrane repair although onset of symptoms is not commonly seen until
      the late teenage years and is often associated with subacute onset and marked
      muscle inflammation. To identify molecular networks specific to dysferlin
      deficient muscle that might explain disease pathogenesis, muscle mRNA profiles
      from 10 mutation-positive LGMD2B/MM patients were compared with a disease control
      [LGMD2I; (n = 9)], and normal muscle samples (n = 11). Query of inflammatory
      pathways suggested LGMD2B-specific increases in co-stimulatory signaling between
      dendritic cells and T cells (CD86, CD28, and CTLA4), associated with localized
      expression of both versican and tenascin. LGMD2B muscle also showed an increase
      in vesicular trafficking pathway proteins not normally observed in muscle
      (synaptotagmin-like protein Slp2a/SYTL2 and the small GTPase Rab27A). We propose
      that Rab27A/Slp2a expression in LGMD2B muscle provides a compensatory vesicular
      trafficking pathway that is able to repair membrane damage in the absence of
      dysferlin. However, this same pathway may release endocytotic vesicle contents,
      resulting in an inflammatory microenvironment. As dysferlin deficiency has been
      shown to enhance phagocytosis by macrophages, together with our findings of
      abnormal myofiber endocytosis pathways and dendritic-T cell activation markers,
      these results suggest a model of immune and inflammatory network over-stimulation
      that may explain the subacute inflammatory presentation.

PMID- 18832577
TI  - Flupirtine as neuroprotective add-on therapy in autoimmune optic neuritis.
AB  - Multiple sclerosis (MS) is a common inflammatory disease of the central nervous
      system that results in persistent impairment in young adults. During chronic
      progressive disease stages, there is a strong correlation between
      neurodegeneration and disability. Current therapies fail to prevent progression
      of neurological impairment during these disease stages. Flupirtine, a drug
      approved for oral use in patients suffering from chronic pain, was used in a rat
      model of autoimmune optic neuritis and significantly increased the survival of
      retinal ganglion cells, the neurons that form the axons of the optic nerve. When
      flupirtine was combined with interferon-beta, an established immunomodulatory
      therapy for MS, visual functions of the animals were improved during the acute
      phase of optic neuritis. Furthermore, flupirtine protected retinal ganglion cells
      from degeneration in a noninflammatory animal model of optic nerve transection.
      Although flupirtine was shown previously to increase neuronal survival by Bcl-2
      up-regulation, this mechanism does not appear to play a role in flupirtine
      mediated protection of retinal ganglion cells either in vitro or in vivo.
      Instead, we showed through patch-clamp investigations that the activation of
      inwardly rectifying potassium channels is involved in flupirtine-mediated
      neuroprotection. Considering the few side effects reported in patients who
      receive long-term flupirtine treatment for chronic pain, our results indicate
      that this drug is an interesting candidate for further evaluation of its
      neuroprotective potential in MS.

PMID- 18832578
TI  - Human autoantibodies specific for neurotrophin receptors TrkA, TrkB, and TrkC
      protect against lethal Trypanosoma cruzi infection in mice.
AB  - Patients with Chagas' disease remain asymptomatic for many years, presumably by
      keeping the etiological agent Trypanosoma cruzi in check through protective
      immunity against. Recently, we found that T. cruzi uses TrkA, a receptor tyrosine
      kinase responsive to neurotrophin nerve growth factor in vertebrate nervous
      systems, to invade cells. We also found that TrkA, TrkB, and TrkC, but not T.
      cruzi, are targets of specific autoantibodies present in the sera of patients
      with chronic Chagas' disease. Here we show that TrkA-, TrkB-, and TrkC-specific
      autoantibodies isolated from the sera of four individuals with chronic
      indeterminate (asymptomatic) Chagas' disease potently blocked invasion of Trk
      bearing neuronal PC12 cells, neuroglial astrocytes, enteroglial cells, and
      Schwann cells and Trk-expressing non-neural smooth muscle and dendritic cells.
      However, these autoantibodies did not inhibit T. cruzi invasion of mutant PC12
      cells lacking TrkA or of normal cells lacking Trk receptors, suggesting that
      autoantibodies interfered with parasite/Trk cross talk to access the
      intracellular milieu. Passive immunization of susceptible and resistant mouse
      strains with very small doses of these autoantibodies reduced parasitemia and
      transferred resistance to an otherwise lethal trypanosome infection. Hence, this
      exquisitely sensitive and unique regulatory immunity against the host (instead of
      parasite) could benefit infected individuals by blocking cellular invasion of the
      obligatory intracellular pathogen, resulting in attenuation of tissue infection
      and clinical manifestations. Such action is contrary to the horror autotoxicus
      frequently associated with microbe-related autoimmune responses.

PMID- 18832579
TI  - Focal adhesion kinase-related proline-rich tyrosine kinase 2 and focal adhesion
      kinase are co-overexpressed in early-stage and invasive ErbB-2-positive breast
      cancer and cooperate for breast cancer cell tumorigenesis and invasiveness.
AB  - Early cancer cell migration and invasion of neighboring tissues are mediated by
      multiple events, including activation of focal adhesion signaling. Key regulators
      include the focal adhesion kinase (FAK) and FAK-related proline-rich tyrosine
      kinase 2 (Pyk2), whose distinct functions in cancer progression remain unclear.
      Here, we compared Pyk2 and FAK expression in breast cancer and their effects on
      ErbB-2-induced tumorigenesis and the potential therapeutic utility of targeting
      Pyk2 compared with FAK in preclinical models of breast cancer. Pyk2 is
      overexpressed in tissues from early and advanced breast cancers and overexpressed
      with both FAK and epidermal growth factor receptor-2 (ErbB-2) in a subset of
      breast cancer cases. Down-regulation of Pyk2 in ErbB-2-positive, FAK-proficient,
      and FAK-deficient cells reduced cell proliferation, which correlated with reduced
      mitogen-activated protein kinase (MAPK) activity. In contrast, Pyk2 silencing had
      little impact on cell migration and invasion. In vivo, Pyk2 down-regulation
      reduced primary tumor growth induced by a metastatic variant of ErbB-2-positive
      MDA 231 breast cancer cells but had little effect on lung metastases in contrast
      to FAK down-regulation. Dual reduction of Pyk2 and FAK expression resulted in
      strong inhibition of both primary tumor growth and lung metastases. Together,
      these data support the cooperative function of Pyk2 and FAK in breast cancer
      progression and suggest that dual inhibition of FAK and Pyk2 is an efficient
      therapeutic approach for targeting invasive breast cancer.

PMID- 18832580
TI  - Conversion of the nipple to hair-bearing epithelia by lowering bone morphogenetic
      protein pathway activity at the dermal-epidermal interface.
AB  - Epithelial appendages, such as mammary glands and hair, arise as a result of
      epithelial-mesenchymal interactions. Bone morphogenetic proteins (BMPs) are
      important for hair follicle morphogenesis and cycling and are known to regulate a
      wide variety of developmental processes. For example, overexpression of BMPs
      inhibits hair follicle formation. We hypothesized that the down-regulation of the
      BMP signaling pathway in the basal epidermis expands regions that are competent
      to form hair follicles and could alter the fate of the epithelium in the mouse
      nipple to a hair-covered epidermal phenotype. To test our hypothesis, we used a
      transgenic mouse model in which keratin 14 (KRT14) promoter-mediated
      overexpression of Noggin, a BMP antagonist, modulates BMP activity. We observed
      the conversion of nipple epithelium into pilosebaceous units. During normal
      mammary gland organogenesis, BMPs are likely used by the nipple epithelium to
      suppress keratinocyte differentiation, thus preventing the formation of
      pilosebaceous units. In this report, we characterize the morphology and processes
      that influence the development of hairs within the nipple of the KRT14-Noggin
      mouse. We demonstrate that Noggin acts, in part, by reducing the BMP signal in
      the epithelium. Reduction of the BMP signal in turn leads to a reduction in the
      levels of parathyroid hormone-related protein. We propose that during evolution
      of the nipple, the BMP pathway was co-opted to suppress hair follicle formation
      and create a more functional milk delivery apparatus.

PMID- 18832581
TI  - Transforming growth factor-beta regulates in vitro heart valve repair by
      activated valve interstitial cells.
AB  - The regulation of valve interstitial cell (VIC) function in response to tissue
      injury and valve disease is not well understood. Because transforming growth
      factor-beta (TGF-beta) has been implicated in tissue repair, we tested the
      hypothesis that TGF-beta is a regulator of VIC activation and associated cell
      responses that occur during early repair processes. We used a well-characterized
      wound model that was created by mechanical denudation of a confluent VIC
      monolayer to study activation and repair 24 hours after wounding. VIC activation
      was demonstrated by immunofluorescent localization of alpha-smooth muscle actin
      (alpha-SMA), and alpha-SMA mRNA levels were quantified by real-time polymerase
      chain reaction. Proliferation and apoptosis were quantified by bromodeoxyuridine
      staining and terminal deoxynucleotidyl transferase dUTP nick end labeling,
      respectively. Repair was quantified by measuring VIC extension into the wound,
      and TGF-beta expression was shown by immunofluorescent localization of
      intracellular TGF-beta. Compared with nonwounded monolayers, VICs at the wound
      edge showed alpha-SMA staining, increased alpha-SMA mRNA content, elongation into
      the wound with stress fibers, proliferation, and apoptosis. VICs at the wound
      edge also showed increased TGF-beta and pSmad2/3 staining with co-expression of
      alpha-SMA. Addition of TGF-beta neutralizing antibody to the wound decreased VIC
      activation, alpha-SMA mRNA content, proliferation, apoptosis, wound closure rate,
      and stress fibers. Conversely, exogenous addition of TGF-beta to the wound
      increased VIC activation, proliferation, wound closure rate, and stress fibers.
      Thus, wounding activates VICs, and TGF-beta signaling modulates VIC response to
      injury.

PMID- 18832582
TI  - Interaction of the Lyme disease spirochete Borrelia burgdorferi with brain
      parenchyma elicits inflammatory mediators from glial cells as well as glial and
      neuronal apoptosis.
AB  - Lyme neuroborreliosis, caused by the spirochete Borrelia burgdorferi, often
      manifests by causing neurocognitive deficits. As a possible mechanism for Lyme
      neuroborreliosis, we hypothesized that B. burgdorferi induces the production of
      inflammatory mediators in the central nervous system with concomitant neuronal
      and/or glial apoptosis. To test our hypothesis, we constructed an ex vivo model
      that consisted of freshly collected slices from brain cortex of a rhesus macaque
      and allowed live B. burgdorferi to penetrate the tissue. Numerous transcripts of
      genes that regulate inflammation as well as oligodendrocyte and neuronal
      apoptosis were significantly altered as assessed by DNA microarray analysis.
      Transcription level increases of 7.43-fold (P = 0.005) for the cytokine tumor
      necrosis factor-alpha and 2.31-fold (P = 0.016) for the chemokine interleukin
      (IL)-8 were also detected by real-time-polymerase chain reaction array analysis.
      The immune mediators IL-6, IL-8, IL-1beta, COX-2, and CXCL13 were visualized in
      glial cells in situ by immunofluorescence staining and confocal microscopy.
      Concomitantly, significant proportions of both oligodendrocytes and neurons
      undergoing apoptosis were present in spirochete-stimulated tissues. IL-6
      production by astrocytes in addition to oligodendrocyte apoptosis were also
      detected, albeit at lower levels, in rhesus macaques that had received in vivo
      intraparenchymal stereotaxic inoculations of live B. burgdorferi. These results
      provide proof of concept for our hypothesis that B. burgdorferi produces
      inflammatory mediators in the central nervous system, accompanied by glial and
      neuronal apoptosis.

PMID- 18832583
TI  - Stress-induced neurogenic inflammation in murine skin skews dendritic cells
      towards maturation and migration: key role of intercellular adhesion molecule
      1/leukocyte function-associated antigen interactions.
AB  - The skin continuously serves as a biosensor of multiple exogenous stressors and
      integrates the resulting responses with an individual's central and peripheral
      endogenous response systems to perceived stress; it also acts to protect against
      external challenges such as wounding and infection. We have previously shown in
      mice that stress induces nerve growth factor- and substance P-dependent
      neurogenic inflammation, which includes the prominent clustering of MHC class
      II(+) cells. Because the contribution of dendritic cells (DCs) in response to
      stress is not well understood, we examined the role of DCs in neurogenic
      inflammation in murine skin using a well-established murine stress model. We show
      that sound stress increases the number of intradermal langerin(+) and CD11c(+)
      DCs and induces DC maturation, as indicated by the up-regulated expression of
      CD11c, MHC class II, and intercellular adhesion molecule-1 (ICAM-1). Blocking of
      ICAM-1/leukocyte function-associated antigen-1 interactions significantly
      abrogated the stress-induced numeric increase, maturation, and migration of
      dermal DCs in vivo and also reduced stress-induced keratinocyte apoptosis and
      endothelial cell expression of ICAM-1. In conclusion, stress exposure causes a
      state of immune alertness in the skin. Such adaptation processes may ensure
      protection from possible infections on wounding by stressors, such as attack by
      predators. However, present-day stressors have changed and such adaptations
      appear redundant and may overrun skin homeostasis by inducing immune dermatoses.

PMID- 18832584
TI  - Shiga toxin-mediated disease in MyD88-deficient mice infected with Escherichia
      coli O157:H7.
AB  - Toll-like receptors (TLRs) are key factors of innate immunity that detect
      pathogen invasion and trigger a host response. TLR4 can mediate a response
      through adaptor molecules, MyD88 or TRIF. In the present study, streptomycin
      treated MyD88(-/-), Tlr4(-/-), Trif (Lps2/Lps2), and C57BL/6 wild-type (WT) mice
      were infected with either Shiga toxin (Stx)-producing or non-producing
      Escherichia coli O157:H7. Moderate to severe clinical signs of disease developed
      in MyD88(-/-) (n = 21/21), Tlr4(-/-) (n = 12/16), Trif (Lps2/Lps2) (n = 7/15) and
      WT mice (n = 6/20) infected with Stx-producing E. coli O157:H7 but not in mice
      inoculated with the Stx non-producing strain (n = 0/54, P < 0.001). MyD88(-/-)
      mice infected with Stx-producing E. coli O157:H7 developed the most severe
      disease and had the highest bacterial burden. Hematological analysis of sick
      MyD88(-/-) mice showed reduced red blood cell counts and reticulocytosis,
      suggesting hemolysis. Thrombocytopenia developed in MyD88(-/-), Trif (Lps2/Lps2),
      and WT mice, and creatinine levels were elevated in both MyD88(-/-) and WT mice
      infected with the Stx-producing strain. Renal histopathology showed evidence of
      glomerular capillary congestion, tubular desquamation, and fibrinogen deposition,
      and intestinal histopathology showed mucosal injury, edema, and inflammation in
      sick mice. Administration of purified Stx2 to MyD88(-/-) and WT mice led to
      severe disease in both groups, suggesting that MyD88(-/-) mice are not more
      sensitive to Stx than WT mice. As MyD88(-/-) mice developed the most severe
      disease hematological and pathological changes, the results suggest that
      dysfunctional innate immune responses via MyD88 enhanced Stx-induced disease.

PMID- 18832585
TI  - Physiological, pathological, and therapeutic implications of zonulin-mediated
      intestinal barrier modulation: living life on the edge of the wall.
AB  - The anatomical and functional arrangement of the gastrointestinal tract suggests
      that this organ, beside its digestive and absorptive functions, regulates the
      trafficking of macromolecules between the environment and the host through a
      barrier mechanism. Under physiological circumstances, this trafficking is
      safeguarded by the competency of intercellular tight junctions, structures whose
      physiological modulation is mediated by, among others, the recently described
      protein zonulin. To prevent harm and minimize inflammation, the same paracellular
      pathway, in concert with the gut-associated lymphoid tissue and the
      neuroendocrine network, controls the equilibrium between tolerance and immunity
      to nonself antigens. The zonulin pathway has been exploited to deliver drugs,
      macromolecules, or vaccines that normally would not be absorbed through the
      gastrointestinal mucosal barrier. However, if the tightly regulated trafficking
      of macromolecules is jeopardized secondary to prolonged zonulin up-regulation,
      the excessive flow of nonself antigens in the intestinal submucosa can cause both
      intestinal and extraintestinal autoimmune disorders in genetically susceptible
      individuals. This new paradigm subverts traditional theories underlying the
      development of autoimmunity, which are based on molecular mimicry and/or the
      bystander effect, and suggests that the autoimmune process can be arrested if the
      interplay between genes and environmental triggers is prevented by re
      establishing intestinal barrier competency. Understanding the role of zonulin
      dependent intestinal barrier dysfunction in the pathogenesis of autoimmune
      diseases is an area of translational research that encompasses many fields.

PMID- 18832586
TI  - CGI-58 is an alpha/beta-hydrolase within lipid transporting lamellar granules of
      differentiated keratinocytes.
AB  - CGI-58 is the causative molecule underlying Dorfman-Chanarin syndrome, a neutral
      lipid storage disease exhibiting apparent clinical features of ichthyosis. CGI
      58, associated with triacylglycerol hydrolysis, has an alpha/beta-hydrolase fold
      and is also known as the alpha/beta-hydrolase domain-containing protein 5. The
      purpose of this study was to elucidate the function of CGI-58 and the pathogenic
      mechanisms of ichthyosis in Dorfman-Chanarin syndrome. Using an anti-CGI-58
      antibody, we found CGI-58 to be expressed in the upper epidermis, predominantly
      in the granular layer cells, as well as in neurons and hepatocytes.
      Immunoelectron microscopy revealed that CGI-58 was also localized to the lamellar
      granules (LGs), which are lipid transport and secretion granules found in
      keratinocytes. CGI-58 expression was markedly reduced in the epidermis of
      patients with harlequin ichthyosis, demonstrating defective LG formation. In
      cultured keratinocytes, CGI-58 expression was mildly up-regulated under high
      Ca(2+) conditions and markedly up-regulated in three-dimensional, organotypic
      cultures. In the developing human epidermis, CGI-58 immunostaining was observed
      at an estimated gestational age of 49 days, and CGI-58 mRNA expression was up
      regulated concomitantly with both epidermal stratification and keratinocyte
      differentiation. CGI-58 knockdown reduced expression of keratinocyte
      differentiation/keratinization markers in cultured human keratinocytes. Our
      results indicate that CGI-58 is expressed and packaged into LGs during
      keratinization and likely plays crucial role(s) in keratinocyte differentiation
      and LG lipid metabolism, contributing to skin lipid barrier formation.

PMID- 18832587
TI  - Defect of hepatocyte growth factor activator inhibitor type 1/serine protease
      inhibitor, Kunitz type 1 (Hai-1/Spint1) leads to ichthyosis-like condition and
      abnormal hair development in mice.
AB  - Hepatocyte growth factor activator inhibitor type 1 (HAI-1)/serine protease
      inhibitor, Kunitz type 1 (SPINT1) is a membrane-bound, serine proteinase
      inhibitor initially identified as an inhibitor of hepatocyte growth factor
      activator. It also inhibits matriptase and prostasin, both of which are membrane
      bound serine proteinases that have critical roles in epidermal differentiation
      and function. In this study, skin and hair phenotypes of mice lacking the Hai
      1/Spint1 gene were characterized. Previously, we reported that the homozygous
      deletion of Hai-1/Spint1 in mice resulted in embryonic lethality attributable to
      impaired placental development. To test the role of Hai-1/Spint1 in mice, the
      placental function of Hai-1/Spint1-mutant mice was rescued. Injection of Hai
      1/Spint1(+/+) blastocysts with Hai-1/Spint1(-/-) embryonic stem cells
      successfully generated high-chimeric Hai-1/Spint1(-/-) embryos (B6Hai-1(-/-High))
      with normal placentas. These embryos were delivered without apparent
      developmental abnormalities, confirming that embryonic lethality of Hai-1/Spint1(
      /-) mice was caused by placental dysfunction. However, newborn B6Hai-1(-/-High)
      mice showed growth retardation and died by 16 days. These mice developed scaly
      skin because of hyperkeratinization, reminiscent of ichthyosis, and abnormal hair
      shafts that showed loss of regular cuticular septation. The interfollicular
      epidermis showed acanthosis with enhanced Akt phosphorylation. Immunoblot
      analysis revealed altered proteolytic processing of profilaggrin in Hai-1/Spint1
      deleted skin with impaired generation of filaggrin monomers. These findings
      indicate that Hai-1/Spint1 has critical roles in the regulated keratinization of
      the epidermis and hair development.

PMID- 18832589
TI  - The role of Lmx1a in the differentiation of human embryonic stem cells into
      midbrain dopamine neurons in culture and after transplantation into a Parkinson's
      disease model.
AB  - Recent studies have provided important insight into the homeoprotein LIM homeobox
      transcription factor 1alpha (Lmx1a) and its role in the commitment of cells to a
      midbrain dopamine (mDA) fate in the developing mouse. We show here that Lmx1a
      also plays a pivotal role in the mDA differentiation of human embryonic stem
      (hES) cells. Thus, as indicated by small interfering RNA experiments, the
      transient early expression of Lmx1a is necessary for the coordinated expression
      of all other dopamine (DA)-specific phenotypic traits as hES cells move from
      multipotent human neural progenitor cells (hNPs) to more restricted precursor
      cells in vitro. Moreover, only Lmx1a-specified hNPs have the potential to
      differentiate into bona fide mDA neurons after transplantation into the 6
      hydroxydopamine-treated rat striatum. In contrast, cortical human neuronal
      precursor cells (HNPCs) and mouse subventricular zone cells do not express Lmx1a
      or become mDA neurons even when placed in an environment that fosters their DA
      differentiation in vitro or in vivo. These findings suggest that Lmx1a may be
      critical to the development of mDA neurons from hES cells and that, along with
      other key early DA markers (i.e., Aldh1a1), may prove to be extremely useful for
      the selection of appropriately staged and suitably mDA-specified hES cells for
      cell replacement in Parkinson's disease.

PMID- 18832590
TI  - Dysregulation of local stem/progenitor cells as a common cellular mechanism for
      heterotopic ossification.
AB  - Heterotopic ossification (HO), the abnormal formation of true marrow-containing
      bone within extraskeletal soft tissues, is a serious bony disorder that may be
      either acquired or hereditary. We utilized an animal model of the genetic
      disorder fibrodysplasia ossificans progressiva to examine the cellular mechanisms
      underlying HO. We found that HO in these animals was triggered by soft tissue
      injuries and that the effects were mediated by macrophages. Spreading of HO
      beyond the initial injury site was mediated by an abnormal adaptive immune
      system. These observations suggest that dysregulation of local stem/progenitor
      cells could be a common cellular mechanism for typical HO irrespective of the
      signal initiating the bone formation.

PMID- 18832592
TI  - Superior osteogenic capacity for bone tissue engineering of fetal compared with
      perinatal and adult mesenchymal stem cells.
AB  - Mesenchymal stem cells (MSCs) from human adult bone marrow (haMSCs) represent a
      promising source for bone tissue engineering. However, their low frequencies and
      limited proliferation restrict their clinical utility. Alternative postnatal,
      perinatal, and fetal sources of MSCs appear to have different osteogenic
      capacities, but have not been systematically compared with haMSCs. We
      investigated the proliferative and osteogenic potential of MSCs from human fetal
      bone marrow (hfMSCs), human umbilical cord (hUCMSCs), and human adult adipose
      tissue (hATMSCs), and haMSCs, both in monolayer cultures and after loading into
      three-dimensional polycaprolactone-tricalcium-phosphate scaffolds.Although all
      MSCs had comparable immunophenotypes, only hfMSCs and hUCMSCs were positive for
      the embryonic pluripotency markers Oct-4 and Nanog. hfMSCs expressed the lowest
      HLA-I level (55% versus 95%-99%) and the highest Stro-1 level (51% versus 10%
      27%), and had the greatest colony-forming unit-fibroblast capacity (1.6x-2.0x; p
      < .01) and fastest doubling time (32 versus 54-111 hours; p < .01). hfMSCs had
      the greatest osteogenic capacity, as assessed by von-Kossa staining, alkaline
      phosphatase activity (5.1x-12.4x; p < .01), calcium deposition (1.6x-2.7x in
      monolayer and 1.6x-5.0x in scaffold culture; p < .01), calcium visualized on
      micro-computed tomography (3.9x17.6x; p < .01) and scanning electron microscopy,
      and osteogenic gene induction. Two months after implantation of cellular
      scaffolds in immunodeficient mice, hfMSCs resulted in the most robust
      mineralization (1.8x-13.3x; p < .01).The ontological and anatomical origins of
      MSCs have profound influences on the proliferative and osteogenic capacity of
      MSCs. hfMSCs had the most proliferative and osteogenic capacity of the MSC
      sources, as well as being the least immunogenic, suggesting they are superior
      candidates for bone tissue engineering.

PMID- 18832593
TI  - Hypoxia and HIF1alpha repress the differentiative effects of BMPs in high-grade
      glioma.
AB  - Hypoxia commonly occurs in solid tumors of the central nervous system (CNS) and
      often interferes with therapies designed to stop their growth. We found that
      pediatric high-grade glioma (HGG)-derived precursors showed greater expansion
      under lower oxygen tension, typical of solid tumors, than normal CNS precursors.
      Hypoxia inhibited p53 activation and subsequent astroglial differentiation of HGG
      precursors. Surprisingly, although HGG precursors generated endogenous bone
      morphogenetic protein (BMP) signaling that promoted mitotic arrest under high
      oxygen tension, this signaling was actively repressed by hypoxia. An acute
      increase in oxygen tension led to Smad activation within 30 minutes, even in the
      absence of exogenous BMP treatment. Treatment with BMPs further promoted
      astroglial differentiation or death of HGG precursors under high oxygen tension,
      but this effect was inhibited under hypoxic conditions. Silencing of hypoxia
      inducible factor 1alpha (HIF1alpha) led to Smad activation even under hypoxic
      conditions, indicating that HIF1alpha is required for BMP repression. Conversely,
      BMP activation at high oxygen tension led to reciprocal degradation of HIF1alpha;
      this BMP-induced degradation was inhibited in low oxygen. These results show a
      novel, mutually antagonistic interaction of hypoxia-response and neural
      differentiation signals in HGG proliferation, and suggest differences between
      normal and HGG precursors that may be exploited for pediatric brain cancer
      therapy.

PMID- 18832594
TI  - A Sox1 to Pax6 switch drives neuroectoderm to radial glia progression during
      differentiation of mouse embryonic stem cells.
AB  - The transcription factors Sox1 and Pax6 are expressed sequentially during early
      mouse embryonic neurogenesis. Sox1 expression starts upon formation of
      neuroectoderm, whereas Pax6 is subsequently expressed in radial glial cells, the
      latter giving rise to most neurons of the cerebral cortex. Here we used mouse
      embryonic stem (ES) cells to study the role of Sox1 and Pax6 in regulating
      differentiation of neural progenitors. For this purpose, we investigated the
      effect of overexpression and knockdown of Sox1 and Pax6, using three
      differentiation protocols. We show that (a) expression of Sox1 or Pax6 in
      uncommitted ES cells favored neuroectodermal lineage choice; (b) continuous Sox1
      expression maintained cells at the neuroepithelial stage and prevented expression
      of Pax6 and other radial glial cell markers; (c) Sox1 knockdown facilitated exit
      from the progenitor stage, whereas Pax6 knockdown decreased formation of radial
      glia; (d) forced Pax6 expression in neuroepithelial cells triggered their
      differentiation into radial glia and neurons; and (e) Pax6 expression induced
      cell migration, a feature typical of radial glia-derived early neurons. We
      conclude that Sox1 enhances neuroectodermal commitment and maintenance but blocks
      further differentiation. In contrast, Pax6 is involved in the progression of
      neuroectoderm toward radial glia.

PMID- 18832595
TI  - IFATS collection: Immunomodulatory effects of adipose tissue-derived stem cells
      in an allergic rhinitis mouse model.
AB  - Adipose tissue-derived stem cells (ASCs) exhibit immunosuppressive effects in
      allogeneic transplantation. However, there is no report that evaluates the in
      vivo immune-modulating effect of ASCs in an experimental allergic rhinitis (AR)
      model. We investigated whether ASCs migrate to the nasal mucosa in an AR mouse
      model and evaluated the immune-modulating effect of ASCs in the AR mouse model.
      Cultured ASCs (2 x 10(6)) were injected i.v. before the first allergen challenge
      in the AR mouse model. Migration of ASCs to the nasal mucosa was evaluated by
      immunofluorescence. The immunomodulatory effects of ASCs were evaluated by nasal
      symptoms, histology, serum ovalbumin (OVA)-specific antibody, and the cytokine
      profile of the spleen. ASCs migrated to the nasal mucosa in the AR mouse model.
      ASCs significantly reduced allergic symptoms and inhibited eosinophilic
      inflammation in the nasal mucosa. ASCs significantly decreased the serum allergen
      specific IgE level and the IgG(1)/IgG(2a) ratio and significantly increased the
      IgG(2a) level in the AR mouse model. ASCs inhibited interleukin (IL)-4 and IL-5
      production from OVA-incubated splenocytes, but enhanced interferon-gamma
      production. In conclusion, ASCs can migrate to the nasal mucosa in the AR mouse
      model and inhibit eosinophilic inflammation partly via shifting to a T-helper 1
      (Th1) from a Th2 immune response to allergens.

PMID- 18832596
TI  - Recognition of galactan components of pectin by galectin-3.
AB  - It has been reported that modified forms of pectin possess anticancer activity.
      To account for this bioactivity, it has been proposed that fragments of pectin
      molecules can act by binding to and inhibiting the various roles of the mammalian
      protein galectin 3 (Gal3) in cancer progression and metastasis. Despite this
      clear molecular hypothesis and evidence for the bioactivity of modified pectin,
      the structural origins of the "bioactive fragments" of pectin molecules are
      currently ill defined. By using a combination of fluorescence microscopy, flow
      cytometry, and force spectroscopy, it has been possible to demonstrate, for the
      first time, specific binding of a pectin galactan to the recombinant form of
      human Gal3. Present studies suggest that bioactivity resides in the neutral sugar
      side chains of pectin polysaccharides and that these components could be isolated
      and modified to optimize bioactivity.

PMID- 18832597
TI  - Human rhomboid family-1 gene RHBDF1 participates in GPCR-mediated transactivation
      of EGFR growth signals in head and neck squamous cancer cells.
AB  - Epidermal growth factor receptor (EGFR) is an activated oncogene in many cancers.
      It can be transactivated by ligands of G protein-coupled receptors (GPCRs). We
      show here that a novel gene, human rhomboid family-1 (RHBDF1), which was recently
      reported to have a pivotal role in epithelial cancer cell growth in culture and
      in xenograft tumors, participates in the modulation of GPCR-mediated EGFR
      transactivation. The RHBDF1 protein localizes mainly in the endoplasmic
      reticulum. Silencing the RHBDF1 gene in head and neck squamous cancer cell line
      1483 cells with siRNA causes an inhibition of gastrin-releasing peptide (GRP) 
      induced phosphorylation of EGFR and EGFR-dependent signaling proteins p44/42 MAPK
      and AKT, accompanied by an inhibition of GRP-induced survival, proliferation, and
      invasion of the cells. The EGFR signaling pathway itself remains intact, however,
      as the cells remain responsive to exogenous EGF. In addition, RHBDF1 gene
      silencing disrupts GRP-stimulated secretion of EGFR ligand TGF-alpha, but not the
      production of latent TGF-alpha, whereas engineered overexpression of RHBDF1
      markedly accelerates the secretion of TGF-alpha. These findings are consistent
      with the view that RHBDF1 is critically involved in a GPCR ligand-stimulated
      process leading to the activation of latent EGFR ligands.

PMID- 18832598
TI  - Intensive insulin therapy in practice: can we do it?
AB  - BACKGROUND: Intensive insulin therapy (IIT) is the standard of care in the ICU,
      but precise implementation of insulin protocols has been difficult in clinical
      practice. The authors' objective was to quantify adherence to an IIT protocol in
      a practice setting, and to describe how adherence impacts overall blood glucose
      (BG) control. METHODS: A retrospective analysis of a cohort of critically ill
      patients treated with IIT was performed. Protocol adherence was evaluated by
      assessing the timing of BG measurements. Each measurement was categorized
      according to the time from the previous reading: early (<1 hour), on time (1-3
      hours), and late (>3 hours). Outcome measures included mean and median BG for
      each time category as well as the proportion of values within the target range.
      RESULTS: In 1106 trauma and surgical ICU patients, 54,139 measurements were
      available for analysis. The overall mean BG (116 mg/dL) was near the target (80
      110 mg/dL), but only 46% of values were within this range. There were 45,806
      (86%) measurements on time, 2749 (5%) early, and 4478 (9%) were late. BG values
      of late measurements were less likely to be within range (34% vs 46% for on time
      measurements, P<.001). Of late measurements, 19% were >200 mg/dL, 13% were 150
      200 mg/dL, and 16% were <60 mg/dL. CONCLUSIONS: IIT is difficult to implement
      precisely in a complex ICU environment. Measurement timing impacts overall BG
      control, with late measurements more often associated with severe hyperglycemic
      (BG>150 mg/dL) and hypoglycemic (BG<60 mg/dL) episodes.

PMID- 18832599
TI  - Musculoskeletal allograft risks and recalls in the United States.
AB  - There have been several improvements to the US tissue banking industry over the
      past decade. Tissue banks had limited active government regulation until 1993, at
      which time the US Food and Drug Administration began regulatory oversight because
      of reports of disease transmission from allograft tissues. Reports in recent
      years of disease transmission associated with the use of allografts have further
      raised concerns about the safety of such implants. A retrospective review of
      allograft recall data was performed to analyze allograft recall by tissue type,
      reason, and year during the period from January 1994 to June 30, 2007. During the
      study period, more than 96.5% of all allograft tissues recalled were
      musculoskeletal. The reasons underlying recent musculoskeletal tissue recalls
      include insufficient or improper donor evaluation, contamination, recipient
      infection, and positive serologic tests. Infectious disease transmission
      following allograft implantation may occur if potential donors are not adequately
      evaluated or screened serologically during the prerecovery phase and if the
      implant is not sterilized before implantation.

PMID- 18832600
TI  - Randomized controlled trials of the treatment of lumbar disk herniation: 1983
      2007.
AB  - Randomized controlled trials are considered to provide the strongest data
      regarding the relative benefits of treatment alternatives for medical conditions.
      Uncertainty persists regarding the optimal treatment of patients with symptomatic
      lumbar disk herniation. Five randomized controlled trials were published between
      1983 and 2007 that compared lumbar diskectomy with nonsurgical treatment. The
      studies enrolled more than 1,000 patients. Inclusion and exclusion criteria were
      generally similar, but there was substantial variation in the outcomes
      measurements used. In all studies, more than one third of patients assigned to
      nonsurgical care crossed over to have surgery. Crossover in the opposite
      direction ranged from 0% to almost 40%. As a result of the large number of
      crossovers, the estimated treatment effect size of diskectomy likely is
      underestimated. Valid inferences about the safety and effectiveness of continued
      nonsurgical care cannot be made. The use of frequentist statistical techniques
      threatens the validity of post hoc subgroup analysis. Large cohort studies and
      alternative statistical techniques may yield more accurate estimates of the
      effectiveness of lumbar diskectomy and aid in identifying patients who may
      benefit from early surgical intervention.

PMID- 18832601
TI  - Elbow arthroscopy.
AB  - Arthroscopy of the elbow was originally considered to be an unsafe procedure
      because of the small size of the elbow joint capsule and its proximity to several
      crucial neurovascular structures. Over the past decade, however, the procedure
      has become safer and more effective. These improvements can be attributed to a
      better understanding of elbow anatomy and of the disorders about the elbow as
      well as to advances in arthroscopic equipment and surgical technique. The most
      common indications for elbow arthroscopy include removal of loose bodies,
      synovectomy, debridement and/or excision of osteophytes, capsular release, and
      the assessment and treatment of osteochondritis dissecans. More recent advances
      have expanded the indications of elbow arthroscopy to include fracture management
      (eg, radial head fractures) and the treatment of lateral epicondylitis.

PMID- 18832602
TI  - Fractures of the proximal phalanx and metacarpals in the hand: preferred methods
      of stabilization.
AB  - Treatment of fractures of the proximal phalanx and metacarpals is based on the
      presentation of the fracture, degree of displacement, and difficulty in
      maintaining fracture reduction. A wide array of treatment options exists for the
      variation in fracture patterns observed. Inherently stable fractures do not
      require surgical treatment; all other fractures should be considered for
      additional stabilization. In general, of the many combinations of internal
      fixation possible, Kirschner wires and screw-and-plate fixation predominate.
      Early closed reduction typically is successful for unicondylar fractures of the
      head of the proximal phalanx. Bicondylar proximal phalanx fractures usually are
      treated with plate fixation. Transverse and short oblique proximal phalanx
      fractures generally are treated with Kirschner wires, although a stable short
      oblique transverse shaft fracture can be managed with an intrinsic plus splint.
      Plate fixation is used in comminuted proximal phalanx as well as comminuted
      metacarpal fractures, and lag screws in spiral long oblique phalanx shaft
      fractures and metacarpal head fractures. Kirschner wire fixation is successful in
      metacarpal neck fractures as well as both short and long transverse oblique shaft
      fractures.

PMID- 18832603
TI  - Surgical management of hip fractures: an evidence-based review of the literature.
      I: femoral neck fractures.
AB  - During the past 10 years, there has been a worldwide effort in all medical fields
      to base clinical health care decisions on available evidence as described by
      thorough reviews of the literature. Hip fractures pose a significant health care
      problem worldwide, with an annual incidence of approximately 1.7 million.
      Globally, the mean age of the population is increasing, and the number of hip
      fractures is expected to triple in the next 50 years. One-year mortality rates
      currently range from 14% to 36%, and care for these patients represents a major
      global economic burden. Surgical options for the management of femoral neck
      fractures are closely linked to individual patient factors and to the location
      and degree of fracture displacement. Nonsurgical management of intracapsular hip
      fractures is limited. Based on a critical, evidence-based review of the current
      literature, we have found minimal differences between implants used for internal
      fixation of displaced fractures. Cemented, unipolar hemiarthroplasty remains a
      good option with reasonable results. In the appropriate patient population,
      outcomes following total hip arthroplasty are favorable and appear to be superior
      to those of internal fixation.

PMID- 18832604
TI  - Management of acute and chronic ankle instability.
AB  - Acute lateral ankle ligament injuries are common. If left untreated, they can
      result in chronic instability. Nonsurgical measures, including functional
      rehabilitation, are the management methods of choice for acute injuries, with
      surgical intervention reserved for high-demand athletes. Chronic lateral ankle
      instability is multifactorial. Failed nonsurgical management after appropriate
      rehabilitation is an indication for surgery. Of the many surgical options
      available, anatomic repair of the anterior talofibular and calcaneofibular
      ligaments is recommended when the quality of the ruptured ligaments permits.
      Anatomic reconstruction with autograft or allograft should be performed when the
      ruptured ligaments are attenuated. Ankle arthroscopy is an important adjunct to
      ligamentous repair and should be performed at the time of repair to identify and
      address intra-articular conditions associated with chronic ankle instability.
      Tenodesis procedures are not recommended because they may disturb ankle and
      hindfoot biomechanics.

PMID- 18832606
TI  - Circulating chromogranin A reveals extra-articular involvement in patients with
      rheumatoid arthritis and curbs TNF-alpha-elicited endothelial activation.
AB  - TNF-alpha plays an important role in the natural history of rheumatoid arthritis
      (RA), a systemic disease characterized by endothelial activation and synovial
      involvement with bone erosions. Neuroendocrine signals contribute as well to RA,
      but their role is poorly understood. We measured in 104 RA patients and in an
      equal number of sex- and age-matched, healthy controls the blood levels of
      chromogranin A (CgA), a candidate marker linking the neuroendocrine system to TNF
      alpha-mediated vascular inflammation. CgA levels were significantly higher in
      patients with RA and remained stable over time. High levels of CgA were
      significantly associated with severe extra-articular manifestations, namely
      pulmonary fibrosis, rheumatoid vasculitis, serositis, and peripheral neuropathy.
      RA sera curbed the response of human microvascular endothelial cells to TNF
      alpha, as assessed by the expression of ICAM-1, the release of MCP-1/CCL2, and
      the export of nuclear high-mobility group box 1; the effect abated in the
      presence of anti-CgA antibodies. The efficacy of the blockade was significantly
      correlated with the CgA concentration in the serum. The recombinant aminoterminal
      portion of CgA, corresponding to residues 1-78, had similar inhibitory effects on
      endothelial cells challenged with TNF-alpha. Our results suggest that enhanced
      levels of CgA identify patients with extra-articular involvement and reveal a
      negative feedback loop that limits the activation of endothelial cells in RA.

PMID- 18832608
TI  - A large excess in apparent solar oblateness due to surface magnetism.
AB  - The shape of the Sun subtly reflects its rotation and internal flows. The surface
      rotation rate, approximately 2 kilometers per second at the equator, predicts an
      oblateness (equator-pole radius difference) of 7.8 milli-arc seconds, or
      approximately 0.001%. Observations from the Reuven Ramaty High-Energy Solar
      Spectroscopic Imager satellite show unexpectedly large flattening, relative to
      the expectation from surface rotation. This excess is dominated by the quadrupole
      term and gives a total oblateness of 10.77 +/- 0.44 milli-arc seconds. The
      position of the limb correlates with a sensitive extreme ultraviolet proxy, the
      284 angstrom limb brightness. We relate the larger radius values to magnetic
      elements in the enhanced network and use the correlation to correct for it as a
      systematic error term in the oblateness measurement. The corrected oblateness of
      the nonmagnetic Sun is 8.01 +/- 0.14 milli-arc seconds, which is near the value
      expected from rotation.

PMID- 18832607
TI  - The 2.6 angstrom crystal structure of a human A2A adenosine receptor bound to an
      antagonist.
AB  - The adenosine class of heterotrimeric guanine nucleotide-binding protein (G
      protein)-coupled receptors (GPCRs) mediates the important role of extracellular
      adenosine in many physiological processes and is antagonized by caffeine. We have
      determined the crystal structure of the human A2A adenosine receptor, in complex
      with a high-affinity subtype-selective antagonist, ZM241385, to 2.6 angstrom
      resolution. Four disulfide bridges in the extracellular domain, combined with a
      subtle repacking of the transmembrane helices relative to the adrenergic and
      rhodopsin receptor structures, define a pocket distinct from that of other
      structurally determined GPCRs. The arrangement allows for the binding of the
      antagonist in an extended conformation, perpendicular to the membrane plane. The
      binding site highlights an integral role for the extracellular loops, together
      with the helical core, in ligand recognition by this class of GPCRs and suggests
      a role for ZM241385 in restricting the movement of a tryptophan residue important
      in the activation mechanism of the class A receptors.

PMID- 18832609
TI  - Molecular confinement accelerates deformation of entangled polymers during
      squeeze flow.
AB  - The squeezing of polymers in narrow gaps is important for the dynamics of
      nanostructure fabrication by nanoimprint embossing and the operation of polymer
      boundary lubricants. We measured stress versus strain behavior while squeezing
      entangled polystyrene films to large strains. In confined conditions where films
      were prepared to a thickness less than the size of the bulk macromolecule,
      resistance to deformation was markedly reduced for both solid-glass forging and
      liquid-melt molding. For melt flow, we further observed a complete inversion of
      conventional polymer viscosity scaling with molecular weight. Our results show
      that squeeze flow is accelerated at small scales by an unexpected influence of
      film thickness in polymer materials.

PMID- 18832610
TI  - Ubiquitin-like protein involved in the proteasome pathway of Mycobacterium
      tuberculosis.
AB  - The protein modifier ubiquitin is a signal for proteasome-mediated degradation in
      eukaryotes. Proteasome-bearing prokaryotes have been thought to degrade proteins
      via a ubiquitin-independent pathway. We have identified a prokaryotic ubiquitin
      like protein, Pup (Rv2111c), which was specifically conjugated to proteasome
      substrates in the pathogen Mycobacterium tuberculosis. Pupylation occurred on
      lysines and required proteasome accessory factor A (PafA). In a pafA mutant,
      pupylated proteins were absent and substrates accumulated, thereby connecting
      pupylation with degradation. Although analogous to ubiquitylation, pupylation
      appears to proceed by a different chemistry. Thus, like eukaryotes, bacteria may
      use a small-protein modifier to control protein stability.

PMID- 18832611
TI  - Natal homing and connectivity in Atlantic bluefin tuna populations.
AB  - Atlantic bluefin tuna populations are in steep decline, and an improved
      understanding of connectivity between individuals from eastern (Mediterranean
      Sea) and western (Gulf of Mexico) spawning areas is needed to manage remaining
      fisheries. Chemical signatures in the otoliths of yearlings from regional
      nurseries were distinct and served as natural tags to assess natal homing and
      mixing. Adults showed high rates of natal homing to both eastern and western
      spawning areas. Trans-Atlantic movement (east to west) was significant and size
      dependent, with individuals of Mediterranean origin mixing with the western
      population in the U.S. Atlantic. The largest (oldest) bluefin tuna collected near
      the northern extent of their range in North American waters were almost
      exclusively of western origin, indicating that this region represents critical
      habitat for the western population.

PMID- 18832612
TI  - A populist movement for health?

PMID- 18832613
TI  - Infectious disease. New malaria plan called ambitious by some, unrealistic by
      others.

PMID- 18832614
TI  - Anthrax investigation. NAS study may fail to settle anthrax case.

PMID- 18832615
TI  - Astroparticle physics. Europeans think big for particle detectors.

PMID- 18832616
TI  - National Institutes of Health. Adding a turn to the roadmap, Zerhouni to step
      down.

PMID- 18832617
TI  - NOAA. U.S. oceans chief leaves a mixed legacy in his 7-year wake.

PMID- 18832618
TI  - Planetary science. Minerals suggest water once flowed on mars--but where?

PMID- 18832619
TI  - Cryptography. Quantum network set to send uncrackable secrets.

PMID- 18832620
TI  - Glaciology. Winds, not just global warming, eating away at the ice sheets.

PMID- 18832621
TI  - Research foundations. Biochemist Robert Tjian named president of Hughes
      Institute.

PMID- 18832622
TI  - Fellowships. An international plan to hatch scientist-entrepreneurs.

PMID- 18832623
TI  - Nutrition science. The peanut butter debate.

PMID- 18832624
TI  - Nutrition science. Patents: a recipe for problems?

PMID- 18832625
TI  - Planetary science. Culture wars over how to find an ancient niche for life on
      Mars.

PMID- 18832626
TI  - Edward Buckler profile. Romping through maize diversity.

PMID- 18832627
TI  - Keeping an eye on the prize.

PMID- 18832628
TI  - Epigenomics: a roadmap, but to where?

PMID- 18832629
TI  - Closing a loophole in the FDA Amendments Act.

PMID- 18832630
TI  - Big payoffs possible for small-molecule screening.

PMID- 18832632
TI  - Astronomy. The shining make-up of our star.

PMID- 18832631
TI  - Agriculture. Sustainable biofuels redux.

PMID- 18832633
TI  - Ecology. Bugs' bugs.

PMID- 18832634
TI  - Atmospheric science. From ocean to stratosphere.

PMID- 18832635
TI  - Chemistry. A light touch catalyzes asymmetric carbon-carbon bond formation.

PMID- 18832636
TI  - Biochemistry. Not comparable, but complementary.

PMID- 18832637
TI  - The origin and evolution of religious prosociality.
AB  - We examine empirical evidence for religious prosociality, the hypothesis that
      religions facilitate costly behaviors that benefit other people. Although
      sociological surveys reveal an association between self-reports of religiosity
      and prosociality, experiments measuring religiosity and actual prosocial behavior
      suggest that this association emerges primarily in contexts where reputational
      concerns are heightened. Experimentally induced religious thoughts reduce rates
      of cheating and increase altruistic behavior among anonymous strangers.
      Experiments demonstrate an association between apparent profession of religious
      devotion and greater trust. Cross-cultural evidence suggests an association
      between the cultural presence of morally concerned deities and large group size
      in humans. We synthesize converging evidence from various fields for religious
      prosociality, address its specific boundary conditions, and point to unresolved
      questions and novel predictions.

PMID- 18832638
TI  - Bacterial protection of beetle-fungus mutualism.
AB  - Host-microbe symbioses play a critical role in the evolution of biological
      diversity and complexity. In a notably intricate system, southern pine beetles
      use symbiotic fungi to help overcome host-tree defenses and to provide nutrition
      for their larvae. We show that this beetle-fungal mutualism is chemically
      mediated by a bacterially produced polyunsaturated peroxide. The molecule's
      selective toxicity toward the beetle's fungal antagonist, combined with the
      prevalence and localization of its bacterial source, indicates an insect-microbe
      association that is both mutualistic and coevolved. This unexpected finding in a
      well-studied system indicates that mutualistic associations between insects and
      antibiotic-producing bacteria are more common than currently recognized and that
      identifying their small-molecule mediators can provide a powerful search strategy
      for therapeutically useful antimicrobial compounds.

PMID- 18832639
TI  - A chronology of Paleozoic sea-level changes.
AB  - Sea levels have been determined for most of the Paleozoic Era (542 to 251 million
      years ago), but an integrated history of sea levels has remained unrealized. We
      reconstructed a history of sea-level fluctuations for the entire Paleozoic by
      using stratigraphic sections from pericratonic and cratonic basins. Evaluation of
      the timing and amplitude of individual sea-level events reveals that the
      magnitude of change is the most problematic to estimate accurately. The long-term
      sea level shows a gradual rise through the Cambrian, reaching a zenith in the
      Late Ordovician, then a short-lived but prominent withdrawal in response to
      Hirnantian glaciation. Subsequent but decreasingly substantial eustatic highs
      occurred in the mid-Silurian, near the Middle/Late Devonian boundary, and in the
      latest Carboniferous. Eustatic lows are recorded in the early Devonian, near the
      Mississippian/Pennsylvanian boundary, and in the Late Permian. One hundred and
      seventy-two eustatic events are documented for the Paleozoic, varying in
      magnitude from a few tens of meters to approximately 125 meters.

PMID- 18832640
TI  - Ultrafast x-ray Thomson scattering of shock-compressed matter.
AB  - Spectrally resolved scattering of ultrafast K-alpha x-rays has provided
      experimental validation of the modeling of the compression and heating of shocked
      matter. The elastic scattering component has characterized the evolution and
      coalescence of two shocks launched by a nanosecond laser pulse into lithium
      hydride with an unprecedented temporal resolution of 10 picoseconds. At shock
      coalescence, we observed rapid heating to temperatures of 25,000 kelvin when the
      scattering spectra show the collective plasmon oscillations that indicate the
      transition to the dense metallic plasma state. The plasmon frequency determines
      the material compression, which is found to be a factor of 3, thereby reaching
      conditions in the laboratory relevant for studying the physics of planetary
      formation.

PMID- 18832641
TI  - Surface-modified carbon nanotubes catalyze oxidative dehydrogenation of n-butane.
AB  - Butenes and butadiene, which are useful intermediates for the synthesis of
      polymers and other compounds, are synthesized traditionally by oxidative
      dehydrogenation (ODH) of n-butane over complex metal oxides. Such catalysts
      require high O2/butane ratios to maintain the activity, which leads to unwanted
      product oxidation. We show that carbon nanotubes with modified surface
      functionality efficiently catalyze the oxidative dehydrogenation of n-butane to
      butenes, especially butadiene. For low O2/butane ratios, a high selectivity to
      alkenes was achieved for periods as long as 100 hours. This process is mildly
      catalyzed by ketonic CO groups and occurs via a combination of parallel and
      sequential oxidation steps. A small amount of phosphorus greatly improved the
      selectivity by suppressing the combustion of hydrocarbons.

PMID- 18832642
TI  - Temperature-induced hydrophobic-hydrophilic transition observed by water
      adsorption.
AB  - The properties of nanoconfined and interfacial water in the proximity of
      hydrophobic surfaces play a pivotal role in a variety of important phenomena such
      as protein folding. Water inside single-walled carbon nanotubes (SWNTs) can
      provide an ideal system for investigating such nanoconfined interfacial water on
      hydrophobic surfaces, provided that the nanotubes can be opened without
      introducing excess defects. Here, we report a hydrophobic-hydrophilic transition
      upon cooling from 22 degrees C to 8 degrees C via the observation of water
      adsorption isotherms in SWNTs measured by nuclear magnetic resonance. A
      considerable slowdown in molecular reorientation of such adsorbed water was also
      detected. The observed transition demonstrates that the structure of interfacial
      water could depend sensitively on temperature, which could lead to intriguing
      temperature dependences involving interfacial water on hydrophobic surfaces.

PMID- 18832643
TI  - Rates of molecular evolution are linked to life history in flowering plants.
AB  - Variable rates of molecular evolution have been documented across the tree of
      life, but the cause of this observed variation within and among clades remains
      uncertain. In plants, it has been suggested that life history traits are
      correlated with the rate of molecular evolution, but previous studies have
      yielded conflicting results. Exceptionally large phylogenies of five major
      angiosperm clades demonstrate that rates of molecular evolution are consistently
      low in trees and shrubs, with relatively long generation times, as compared with
      related herbaceous plants, which generally have shorter generation times. Herbs
      show much higher rates of molecular change but also much higher variance in
      rates. Correlates of life history attributes have long been of interest to
      biologists, and our results demonstrate how changes in the rate of molecular
      evolution that are linked to life history traits can affect measurements of the
      tempo of evolution as well as our ability to identify and conserve biodiversity.

PMID- 18832644
TI  - Molecular architecture of the "stressosome," a signal integration and
      transduction hub.
AB  - A commonly used strategy by microorganisms to survive multiple stresses involves
      a signal transduction cascade that increases the expression of stress-responsive
      genes. Stress signals can be integrated by a multiprotein signaling hub that
      responds to various signals to effect a single outcome. We obtained a medium
      resolution cryo-electron microscopy reconstruction of the 1.8-megadalton
      "stressosome" from Bacillus subtilis. Fitting known crystal structures of
      components into this reconstruction gave a pseudoatomic structure, which had a
      virus capsid-like core with sensory extensions. We suggest that the different
      sensory extensions respond to different signals, whereas the conserved domains in
      the core integrate the varied signals. The architecture of the stressosome
      provides the potential for cooperativity, suggesting that the response could be
      tuned dependent on the magnitude of chemophysical insult.

PMID- 18832645
TI  - A physical map of the 1-gigabase bread wheat chromosome 3B.
AB  - As the staple food for 35% of the world's population, wheat is one of the most
      important crop species. To date, sequence-based tools to accelerate wheat
      improvement are lacking. As part of the international effort to sequence the 17
      billion-base-pair hexaploid bread wheat genome (2n = 6x = 42 chromosomes), we
      constructed a bacterial artificial chromosome (BAC)-based integrated physical map
      of the largest chromosome, 3B, that alone is 995 megabases. A chromosome-specific
      BAC library was used to assemble 82% of the chromosome into 1036 contigs that
      were anchored with 1443 molecular markers, providing a major resource for genetic
      and genomic studies. This physical map establishes a template for the remaining
      wheat chromosomes and demonstrates the feasibility of constructing physical maps
      in large, complex, polyploid genomes with a chromosome-based approach.

PMID- 18832646
TI  - Ceramide biogenesis is required for radiation-induced apoptosis in the germ line
      of C. elegans.
AB  - Ceramide engagement in apoptotic pathways has been a topic of controversy. To
      address this controversy, we tested loss-of-function (lf) mutants of conserved
      genes of sphingolipid metabolism in Caenorhabditis elegans. Although somatic
      (developmental) apoptosis was unaffected, ionizing radiation-induced apoptosis of
      germ cells was obliterated upon inactivation of ceramide synthase and restored
      upon microinjection of long-chain natural ceramide. Radiation-induced increase in
      the concentration of ceramide localized to mitochondria and was required for BH3
      domain protein EGL-1-mediated displacement of CED-4 (an APAF-1-like protein) from
      the CED-9 (a Bcl-2 family member)/CED-4 complex, an obligate step in activation
      of the CED-3 caspase. These studies define CEP-1 (the worm homolog of the tumor
      suppressor p53)-mediated accumulation of EGL-1 and ceramide synthase-mediated
      generation of ceramide through parallel pathways that integrate at mitochondrial
      membranes to regulate stress-induced apoptosis.

PMID- 18832647
TI  - Lacking control increases illusory pattern perception.
AB  - We present six experiments that tested whether lacking control increases illusory
      pattern perception, which we define as the identification of a coherent and
      meaningful interrelationship among a set of random or unrelated stimuli.
      Participants who lacked control were more likely to perceive a variety of
      illusory patterns, including seeing images in noise, forming illusory
      correlations in stock market information, perceiving conspiracies, and developing
      superstitions. Additionally, we demonstrated that increased pattern perception
      has a motivational basis by measuring the need for structure directly and showing
      that the causal link between lack of control and illusory pattern perception is
      reduced by affirming the self. Although these many disparate forms of pattern
      perception are typically discussed as separate phenomena, the current results
      suggest that there is a common motive underlying them.

PMID- 18832650
TI  - Suplatast tosilate prevents bleomycin-induced pulmonary fibrosis in mice.
AB  - Increasing evidence suggests that the development of pulmonary fibrosis is a T
      helper (Th) 2-mediated process. Suplatast tosilate is a Th2 cytokine inhibitor
      that is widely used as an asthma controller in Japan. Therefore, we hypothesized
      that suplatast tosilate might have an inhibitory effect on the development of
      pulmonary fibrosis. To investigate this effect, suplatast tosilate was
      administered to mice after the intratracheal instillation of bleomycin (BLM). The
      effect of suplatast tosilate was studied by analysis of bronchoalveolar lavage
      (BAL) fluid and a hydroxyproline assay. We found that the treatment of mice with
      suplatast tosilate significantly reduced the degree of pulmonary fibrosis.
      Because a significantly elevated Th2 response was not detected in the C57BL/6
      mice after BLM administration, the effect of suplatast tosilate on Th2 cytokines
      could not be demonstrated. Interestingly, however, the up-regulation of the
      monocyte chemoattractant protein (MCP)-1 levels in the BAL fluid was found to be
      suppressed. Following these results, we also demonstrated that suplatast tosilate
      effectively inhibited the production of MCP-1 in alveolar macrophages (AMs).
      These findings suggest that suplatast tosilate has both anti-inflammatory and
      antifibrotic effects, which were associated with a suppressed MCP-1 expression in
      AMs. Thus, suplatast tosilate, which is already widely used in Japan, may warrant
      further consideration as a potentially useful treatment for pulmonary fibrosis.

PMID- 18832649
TI  - Distinct roles of estrogen receptor-alpha and beta in the modulation of vascular
      inducible nitric-oxide synthase in diabetes.
AB  - Estrogen is known to affect vascular function and diabetes development, but the
      relative contribution of estrogen receptor (ER) isoforms is unclear. The aim of
      this study was to determine how individual ER isoforms modulate inflammatory
      enzymes in the vascular wall of control and streptozotocin (STZ)-injected
      rodents. Primary cultures of rat aortic smooth muscle cells (SMCs) were
      stimulated with inflammatory agents in the presence or absence of increasing
      concentrations of the ER alpha and ER beta-selective agonists 4,4',4''-(4-propyl
      [1H]-pyrazole-1,3,5-triyl)trisphenol (PPT) and diarylpropionitrile (DPN),
      respectively. The production of inducible nitric-oxide synthase (iNOS), a
      classical indicator of vascular inflammation, was significantly reduced by PPT in
      control but not diabetic SMCs, whereas it was further enhanced by DPN treatment
      in both groups. This distinct action profile was not related to changes in ER
      transcriptional activity. However, extracellular signal-regulated kinase 1/2
      signaling was activated by DPN but not by PPT in cytokine-treated SMCs. In
      cultured aortic rings from both normoglycemic and STZ-diabetic mice,
      pharmacological activation of ER alpha attenuated cytokine-driven iNOS induction
      by 30 to 50%. Vascular iNOS levels were decreased consistently when adding 1 nM
      17beta-estradiol to aortic tissues from ER beta- but not ER alpha-knockout mice.
      These findings suggest a possible role for ER alpha-selective ligands in reducing
      vascular inflammatory responses under normo- and hyperglycemic conditions.

PMID- 18832651
TI  - Host CD4+CD25+ T cells can expand and comprise a major component of the Treg
      compartment after experimental HCT.
AB  - Reconstitution of the recipient lymphoid compartment following hematopoietic cell
      transplantation (HCT) is typically delayed. The present studies investigated the
      residual host CD4(+)CD25(+)Foxp3(+) (Treg) compartment after several conditioning
      regimens, including T cell-depleted and T cell-replete HCT and observed (1) a
      small number of recipient Treg cells survived aggressive conditioning; (2) the
      surviving, that is, residual Tregs underwent marked expansion; and (3) recipient
      CD4(+)FoxP3(+) cells composed the majority of the Treg compartment for several
      months post-syngeneic HCT. Notably, residual Tregs also dominated the compartment
      post-HCT with T cell-depleted (TCD) major histocompatibility complex-matched
      allogeneic bone marrow but not following T cell-replete transplantations. The
      residual Treg cell compartment was functionally competent as assessed by in vitro
      lymphoid suppression and in vivo autoimmune disease transfer assay. These
      observations support the notion that functional host Tregs initially occupy a
      niche in lymphopenic transplantation recipients, undergo significant expansion,
      and contribute to the compartment for an extended period before donor-derived
      CD4(+)FoxP3(+) T cells eventually compose the majority of the compartment. In
      total, the findings suggest that the presence of host Tregs may be important to
      consider regarding elicitation of immune (eg, antitumor, vaccine) responses in
      recipients during the early post-transplant period involving autologous and
      certain allogeneic HCT regimens.

PMID- 18832652
TI  - A biomarker panel for acute graft-versus-host disease.
AB  - No validated biomarkers exist for acute graft-versus-host disease (GVHD). We
      screened plasma with antibody microarrays for 120 proteins in a discovery set of
      42 patients who underwent transplantation that revealed 8 potential biomarkers
      for diagnostic of GVHD. We then measured by enzyme-linked immunosorbent assay
      (ELISA) the levels of these biomarkers in samples from 424 patients who underwent
      transplantation randomly divided into training (n = 282) and validation (n = 142)
      sets. Logistic regression analysis of these 8 proteins determined a composite
      biomarker panel of 4 proteins (interleukin-2-receptor-alpha, tumor-necrosis
      factor-receptor-1, interleukin-8, and hepatocyte growth factor) that optimally
      discriminated patients with and without GVHD. The area under the receiver
      operating characteristic curve distinguishing these 2 groups in the training set
      was 0.91 (95% confidence interval, 0.87-0.94) and 0.86 (95% confidence interval,
      0.79-0.92) in the validation set. In patients with GVHD, Cox regression analysis
      revealed that the biomarker panel predicted survival independently of GVHD
      severity. A panel of 4 biomarkers can confirm the diagnosis of GVHD in patients
      at onset of clinical symptoms of GVHD and provide prognostic information
      independent of GVHD severity.

PMID- 18832653
TI  - NKT-cell help to B lymphocytes can occur independently of cognate interaction.
AB  - CD4(+) T (Th)-cell help to B lymphocytes requires cognate interaction and CD40
      engagement. Invariant natural killer T (iNKT) cells are innate-like T lymphocytes
      that recognize alphagalactosylceramide (alphaGalCer) presented by CD1d, and can
      help B-cell responses. We asked whether alphaGalCer-activated iNKT cells help B
      lymphocytes through cognate interaction, or indirectly, via enhancement of Th-B
      cell interaction. After immunization with protein Ags and alphaGalCer, antibody
      titers were assessed in wild-type or splenectomized mice, and in bone marrow
      radiation chimeras lacking CD1d or CD40 expression on B lymphocytes, or
      expressing CD1d or MHC II disjointly on antigen-presenting cells (APCs). We find
      that alphaGalCer-dependent enhancement of B-cell response (1) can occur when B
      cells do not express CD1d but express CD40; (2) requires that iNKT and Th cells
      interact with the same APCs that coexpress both CD1d and MHC-II; and (3) takes
      place without spleen. These findings demonstrate alphaGalCer-induced help for
      antibody responses can occur without cognate iNKT/B-cell interaction, and suggest
      this help entails activation of APCs by iNKT cells, which in turn activate Th
      cells and their helper functions for B cells. Thus, the alphaGalCer-induced help
      recapitulates the function of classical adjuvants that stimulate the innate
      immune system to support adaptive immune responses.

PMID- 18832654
TI  - Wnt3a deficiency irreversibly impairs hematopoietic stem cell self-renewal and
      leads to defects in progenitor cell differentiation.
AB  - Canonical Wnt signaling has been implicated in various aspects of hematopoiesis.
      Its role is controversial due to different outcomes between various inducible Wnt
      signaling loss-of-function models and also compared with gain-of-function
      systems. We therefore studied a mouse deficient for a Wnt gene that seemed to
      play a nonredundant role in hematopoiesis. Mice lacking Wnt3a die prenatally
      around embryonic day (E) 12.5, allowing fetal hematopoiesis to be studied using
      in vitro assays and transplantation into irradiated recipient mice. Here we show
      that Wnt3a deficiency leads to a reduction in the numbers of hematopoietic stem
      cells (HSCs) and progenitor cells in the fetal liver (FL) and to severely reduced
      reconstitution capacity as measured in secondary transplantation assays. This
      deficiency is irreversible and cannot be restored by transplantation into Wnt3a
      competent mice. The impaired long-term repopulation capacity of Wnt3a(-/-) HSCs
      could not be explained by altered cell cycle or survival of primitive
      progenitors. Moreover, Wnt3a deficiency affected myeloid but not B-lymphoid
      development at the progenitor level, and affected immature thymocyte
      differentiation. Our results show that Wnt3a signaling not only provides
      proliferative stimuli, such as for immature thymocytes, but also regulates cell
      fate decisions of HSC during hematopoiesis.

PMID- 18832655
TI  - Aberrant DNA methylation is a dominant mechanism in MDS progression to AML.
AB  - Myelodysplastic syndromes (MDSs) are clonal hematologic disorders that frequently
      represent an intermediate disease stage before progression to acute myeloid
      leukemia (AML). As such, study of MDS/AML can provide insight into the mechanisms
      of neoplastic evolution. In 184 patients with MDS and AML, DNA methylation
      microarray and high-density single nucleotide polymorphism array (SNP-A)
      karyotyping were used to assess the relative contributions of aberrant DNA
      methylation and chromosomal deletions to tumor-suppressor gene (TSG) silencing
      during disease progression. Aberrant methylation was seen in every sample, on
      average affecting 91 of 1505 CpG loci in early MDS and 179 of 1505 loci after
      blast transformation (refractory anemia with excess blasts [RAEB]/AML). In
      contrast, chromosome aberrations were seen in 79% of early MDS samples and 90% of
      RAEB/AML samples, and were not as widely distributed over the genome. Analysis of
      the most frequently aberrantly methylated genes identified FZD9 as a candidate
      TSG on chromosome 7. In patients with chromosome deletion at the FZD9 locus,
      aberrant methylation of the remaining allele was associated with the poorest
      clinical outcome. These results indicate that aberrant methylation can cooperate
      with chromosome deletions to silence TSG. However, the ubiquity, extent, and
      correlation with disease progression suggest that aberrant DNA methylation is the
      dominant mechanism for TSG silencing and clonal variation in MDS evolution to
      AML.

PMID- 18832656
TI  - Endothelial progenitor cell homing: prominent role of the IGF2-IGF2R-PLCbeta2
      axis.
AB  - Homing of endothelial progenitor cells (EPCs) to the neovascular zone is now
      considered to be an essential step in the formation of vascular networks during
      embryonic development and also for neovascularization in postnatal life. We
      report here the prominent role of the insulin-like growth factor 2 (IGF2)/IGF2
      receptor (IGF2R) system in promoting EPC homing. With high-level expression of
      IGF2R in EPCs, IGF2-induced hypoxic conditions stimulated multiple steps of EPC
      homing in vitro and promoted both EPC recruitment and incorporation into the
      neovascular area, resulting in enhanced angiogenesis in vivo. Remarkably, all
      IGF2 actions were exerted predominantly through IGF2R-linked G(i) protein
      signaling and required intracellular Ca(2+) mobilization induced by the beta2
      isoform of phospholipase C. Together, these findings indicate that locally
      generated IGF2 at either ischemic or tumor sites may contribute to postnatal
      vasculogenesis by augmenting the recruitment of EPCs. The utilization of the
      IGF2/IGF2R system may therefore be useful for the development of novel means to
      treat angiogenesis-dependent diseases.

PMID- 18832657
TI  - Mesenchymal stem cells induce mature dendritic cells into a novel Jagged-2
      dependent regulatory dendritic cell population.
AB  - Mesenchymal stem cells (MSCs), in addition to their multilineage differentiation,
      exert immunomodulatory effects on immune cells, even dendritic cells (DCs).
      However, whether they influence the destiny of full mature DCs (maDCs) remains
      controversial. Here we report that MSCs vigorously promote proliferation of
      maDCs, significantly reduce their expression of Ia, CD11c, CD80, CD86, and CD40
      while increasing CD11b expression. Interestingly, though these phenotypes clearly
      suggest their skew to immature status, bacterial lipopolysaccharide (LPS)
      stimulation could not reverse this trend. Moreover, high endocytosic capacity,
      low immunogenicity, and strong immunoregulatory function of MSC-treated maDCs
      (MSC-DCs) were also observed. Furthermore we found that MSCs, partly via cell
      cell contact, drive maDCs to differentiate into a novel Jagged-2-dependent
      regulatory DC population and escape their apoptotic fate. These results further
      support the role of MSCs in preventing rejection in organ transplantation and
      treatment of autoimmune disease.

PMID- 18832658
TI  - Human C/EBP-epsilon activator and repressor isoforms differentially reprogram
      myeloid lineage commitment and differentiation.
AB  - CCAAT enhancer-binding protein-epsilon (C/EBP-epsilon) is required for the
      terminal differentiation of neutrophils and eosinophils. Human C/EBP-epsilon is
      expressed as 4 isoforms (32, 30, 27, and 14 kDa) through differential RNA
      splicing, and alternative promoters and translational start sites. The C/EBP
      epsilon(32/30) isoforms are transcriptional activators, whereas C/EBP-epsilon(27)
      interacts with and represses GATA-1 transactivation of eosinophil promoters.
      C/EBP-epsilon(14) contains only DNA-binding and -dimerization domains and may
      function as a dominant-negative regulator. To define functional activities for
      these C/EBP-epsilon isoforms in myelopoiesis, human CD34(+) progenitors were
      transduced with internal ribosomal entry site-enhanced green fluorescent protein
      retroviral vectors encoding the 32/30, 27, and 14-kDa isoforms, purified by
      fluorescence-activated cell sorter, and analyzed in colony-forming assays and
      suspension cultures. Progenitors transduced with C/EBP-epsilon(32/30) default
      exclusively to eosinophil differentiation and gene expression, independent of
      interleukin-5, and regardless of inclusion of cytokines to induce other lineages.
      In contrast, the putative repressor C/EBP-epsilon(27) isoform strongly inhibits
      eosinophil differentiation and gene expression, including GATA-1, promoting
      granulocyte (neutrophil)-macrophage differen-tiation. The C/EBP-epsilon(14)
      repressor isoform strongly inhibits eosinophil development and gene expression,
      promoting erythroid differentiation, an effect enhanced by erythropoietin. Thus,
      C/EBP-epsilon isoforms can reprogram myeloid lineage commitment and
      differentiation consistent with their predicted activities based on activator and
      repressor domains and in vitro functional activities.

PMID- 18832659
TI  - Orai1 (CRACM1) is the platelet SOC channel and essential for pathological
      thrombus formation.
AB  - Platelet activation and aggregation at sites of vascular injury are essential for
      primary hemostasis, but are also major pathomechanisms underlying myocardial
      infarction and stroke. Changes in [Ca(2+)](i) are a central step in platelet
      activation. In nonexcitable cells, receptor-mediated depletion of intracellular
      Ca(2+) stores triggers Ca(2+) entry through store-operated calcium (SOC)
      channels. STIM1 has been identified as an endoplasmic reticulum (ER)-resident
      Ca(2+) sensor that regulates store-operated calcium entry (SOCE) in immune cells
      and platelets, but the identity of the platelet SOC channel has remained elusive.
      Orai1 (CRACM1) is the recently discovered SOC (CRAC) channel in T cells and mast
      cells but its role in mammalian physiology is unknown. Here we report that Orai1
      is strongly expressed in human and mouse platelets. To test its role in blood
      clotting, we generated Orai1-deficient mice and found that their platelets
      display severely defective SOCE, agonist-induced Ca(2+) responses, and impaired
      activation and thrombus formation under flow in vitro. As a direct consequence,
      Orai1 deficiency in mice results in resistance to pulmonary thromboembolism,
      arterial thrombosis, and ischemic brain infarction, but only mild bleeding time
      prolongation. These results establish Orai1 as the long-sought platelet SOC
      channel and a crucial mediator of ischemic cardiovascular and cerebrovascular
      events.

PMID- 18832660
TI  - Functional alteration of red blood cells by a megadalton protein of Plasmodium
      falciparum.
AB  - Proteins exported from Plasmodium falciparum parasites into red blood cells
      (RBCs) interact with the membrane skeleton and contribute to the pathogenesis of
      malaria. Specifically, exported proteins increase RBC membrane rigidity, decrease
      deformability, and increase adhesiveness, culminating in intravascular
      sequestration of infected RBCs (iRBCs). Pf332 is the largest (>1 MDa) known
      malaria protein exported to the RBC membrane, but its function has not previously
      been determined. To determine the role of Pf332 in iRBCs, we have engineered and
      analyzed transgenic parasites with Pf332 either deleted or truncated. Compared
      with RBCs infected with wild-type parasites, mutants lacking Pf332 were more
      rigid, were significantly less adhesive to CD36, and showed decreased expression
      of the major cytoadherence ligand, PfEMP1, on the iRBC surface. These
      abnormalities were associated with dramatic morphologic changes in Maurer clefts
      (MCs), which are membrane structures that transport malaria proteins to the RBC
      membrane. In contrast, RBCs infected with parasites expressing truncated forms of
      Pf332, although still hyperrigid, showed a normal adhesion profile and
      morphologically normal MCs. Our results suggest that Pf332 both modulates the
      level of increased RBC rigidity induced by P falciparum and plays a significant
      role in adhesion by assisting transport of PfEMP1 to the iRBC surface.

PMID- 18832661
TI  - Imaging preventable infarction in patients with acute ischemic stroke.
AB  - One of the goals of neuroimaging in acute ischemic stroke is to identify those
      patients whose outcome will be improved by therapeutic intervention. This article
      will discuss the design, analysis, and interpretation of clinical research
      studies carried out to establish the accuracy and clinical value of neuroimaging
      to select such patients.

PMID- 18832662
TI  - A novel quantitative simple brain metric using MR imaging for preterm infants.
AB  - BACKGROUND AND PURPOSE: The application of volumetric techniques to preterm
      infants has revealed brain volume reductions. Such quantitative data are not
      available in routine neonatal radiologic care. The objective of this study was to
      develop simple brain metrics to compare brain size in preterm and term infants
      and to correlate these metrics with brain volumes from volumetric MR imaging
      techniques. MATERIALS AND METHODS: MR images from 189 preterm infants <30 weeks'
      gestational age or <1250 g birthweight scanned at term-equivalent age and 36 term
      infants were studied. Fifteen tissue and fluid measures were systematically
      evaluated on 4 selected sections. The results were correlated with total brain,
      gray matter, white matter, and CSF volumes. RESULTS: The mean bifrontal,
      biparietal, and transverse cerebellar diameters were reduced (-11.6%, 95%
      confidence interval [CI], -13.8% to -9.3%; -12%, 95% CI, -14% to -9.8%; and 
      8.7%, 95% CI, -10.5% to -7% respectively) and the mean left ventricle diameter
      was increased (+22.3%, 95% CI, 2.9%-41.6%) in preterm infants (P < .01). Strong
      correlations were found between the bifrontal and biparietal measures with total
      brain tissue volume, whereas the size of the ventricles and the interhemispheric
      measure correlated with CSF volume. Intraobserver reliability was high
      (intraclass correlation coefficients [ICC], >0.7), where interobserver agreement
      was acceptable for tissue measures (ICC, >0.6) but lower for fluid measures (ICC,
      <0.4). CONCLUSIONS: Simple brain metrics at term-equivalent age showed smaller
      brain diameters and increased ventricle size in preterm infants compared with
      full-term infants. These measures represent a reliable and easily applicable
      method to quantify brain growth and assess brain atrophy in this at-risk
      population.

PMID- 18832663
TI  - Phase-contrast MR imaging support for the diagnosis of aqueductal stenosis.
AB  - BACKGROUND AND PURPOSE: Patients with aqueductal stenosis (AS) present with
      various clinical and radiologic features. Conventional MR imaging provides useful
      information in AS but depends on a subjective evaluation by the neuroradiologist.
      The purpose of this study was to evaluate the support of the phase-contrast MR
      imaging (PC-MR imaging) technique (sensitive to CSF flows) for the diagnosis of
      AS. MATERIALS AND METHODS: We retrospectively considered 17 patients who
      underwent PC-MR imaging to explore hydrocephalus, with the absence of CSF flow at
      the aqueductal level. We analyzed their clinical and morphologic MR imaging data.
      RESULTS: None of the usually reported direct or indirect signs of aqueductal
      obstruction were seen in 7 patients in whom the clinical suggestion of AS was
      confirmed by PC-MR imaging results. Seven patients in this population had a third
      ventriculostomy, and 5 of them were among those in whom conventional MR imaging
      failed to reveal signs of aqueductal obstruction. All of these 7 patients had a
      positive postsurgical outcomes. The analysis of CSF and vascular dynamic data in
      this population was compared with an aged-matched population, and these data were
      found similar except for the fourth ventricular CSF flush flow latency.
      CONCLUSIONS: PC-MR imaging supports the diagnosis of CSF flow blockage at the
      aqueductal level in a reliable, reproducible, and rapid way, which aids in the
      diagnosis of AS in patients with clinical and/or radiologic suggestion of
      obstructive hydrocephalus. We, therefore, suggest using this technique in the
      current evaluation of hydrocephalus.

PMID- 18832664
TI  - MR imaging and quantification of the movement of the lamina terminalis depending
      on the CSF dynamics.
AB  - BACKGROUND AND PURPOSE: Brain pulsation is a well-known observation in
      neurosurgery, but methods for its visualization on MR imaging, like phase
      imaging, do not provide a detailed structural view. We prospectively investigated
      electrocardiographic (ECG)-gated cine true fast imaging with steady-state
      precession (FISP) sequence on volunteers to test a sequence for demonstrating
      brain pulsation and movements of intracranial structures related to CSF dynamics.
      MATERIALS AND METHODS: Eleven healthy volunteers were investigated with
      prospectively ECG-gated cine true-FISP in the midsagittal plane. A total of 50
      phases were recorded per cardiac cycle and per volunteer. The lamina terminalis
      was chosen to study the pulsatility of the brain, and the optic recess diameter
      was chosen for means of objective quantification of the degree of pulsatility.
      RESULTS: Pulsatile motion of the lamina terminalis was apparent in all volunteers
      on the cine mode. The mean diameter of the optic recess was 2.5 mm. The greatest
      change in diameter in 1 volunteer was 1.5 mm. The mean change in diameter was 40%
      during 1 cardiac cycle. CONCLUSIONS: Cine true-FISP sequence is a well-suited
      method for investigations of passive movements of the ventricular system. It
      shows pulsations of the brain as well as passive changes caused by CSF dynamics
      with high temporal and spatial resolution.

PMID- 18832665
TI  - Quantitative fiber tracking analysis of the optic radiation correlated with
      visual performance in premature newborns.
AB  - BACKGROUND AND PURPOSE: Many prematurely born neonates have abnormalities of
      vision or visual processing. This study tests the hypothesis that a correlation
      exists between the microstructure of the optic radiation and visual performance
      in premature neonates. MATERIALS AND METHODS: Diffusion tensor imaging (DTI) was
      performed on 36 premature neonates ranging in age from 29 to 41 weeks of
      gestational age (GA) at time of MR imaging. DTI fiber tracking methods were
      developed to delineate the optic radiations and segment the tract into anterior,
      middle, and posterior regions. Structural development and spatial heterogeneity
      in the delineated optic radiations were quantitatively assessed with diffusion
      tensor parameters including fractional anisotropy (FA), directionally averaged
      diffusivity (D(av)), parallel diffusivity (lambda(1)), and transverse diffusivity
      (lambda( perpendicular)). Visual maturity of the preterm neonates at the time of
      MR imaging was assessed with a visual fixation task. Regression analysis was used
      to examine the relationship between neonatal visual performance and the
      microstructure of the optic radiation. RESULTS: Fractional anisotropy within the
      optic radiation was observed to increase with GA (P < .0001). D(av), parallel
      diffusivity, and transverse diffusivity within the optic radiation each decreased
      with GA (P < .0003, P < .02, and P < .0001, respectively). The anterior segment
      of the optic radiation exhibited higher FA and lower D(av), parallel diffusivity,
      and transverse diffusivity (P < .005 each) than within the middle and posterior
      segments. Optic radiation fractional anisotropy correlated significantly with
      scores from the visual fixation tracking assessment, independent of GA (P <
      .006). CONCLUSIONS: This study detected a significant link between the tissue
      architecture of the optic radiation and visual function in premature neonates.

PMID- 18832666
TI  - The jugular foramen: imaging strategy and detailed anatomy at 3T.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to assess how well the
      anatomy of the jugular foramen (JF) could be displayed by 3T MR imaging by using
      a 3D contrast-enhanced fast imaging employing steady-state acquisition sequence
      (CE-FIESTA) and a 3D contrast-enhanced MR angiographic sequence (CE-MRA).
      MATERIALS AND METHODS: Twenty-five patients free of skull base lesions were
      imaged on a 3T MR imaging scanner using CE-FIESTA and CE-MRA. Two readers
      analyzed the images in collaboration, with the following objectives: 1) to score
      the success with which these sequences depicted the glossopharyngeal (CNIX) and
      vagus (CNX) nerves, their ganglia, and the spinal root of the accessory nerve
      (spCNXI) within the JF, and 2) to determine the value of anatomic landmarks for
      the in vivo identification of these structures. RESULTS: CE-FIESTA and CE-MRA
      displayed CNIX in 90% and 100% of cases, respectively, CNX in 94% and 100%, and
      spCNXI in 51% and 0% of cases. The superior ganglion of CNIX was discernible in
      89.8% and 87.8%; the inferior ganglion of CNIX, in 73% and 100%; and the superior
      ganglion of CNX, in 98% and 100% of cases. Landmarks useful for identifying these
      structures were the inferior petrosal sinus and the external opening of the
      cochlear aqueduct. CONCLUSIONS: This study protocol is excellent for displaying
      the complex anatomy of the JF and related structures. It is expected to aid in
      detecting small pathologies affecting the JF and in planning the best surgical
      approach to lesions affecting the JF.

PMID- 18832667
TI  - Comment on "Molecular basis of the dual functions of 2B4 (CD244)".

PMID- 18832668
TI  - Homeostatic regulation of blood neutrophil counts.
AB  - Blood neutrophil counts are determined by the differentiation and proliferation
      of precursor cells, the release of mature neutrophils from the bone marrow,
      margination, trafficking and transmigration through the endothelial lining,
      neutrophil apoptosis, and uptake by phagocytes. This brief review summarizes the
      regulation of blood neutrophil counts, which is in part controlled by G-CSF, IL
      17, and IL-23. Neutrophils are retained in the bone marrow through interaction of
      CXCL12 with its receptor CXCR4. The relevance of this mechanism is illustrated by
      rare diseases in which disrupting the desensitization of CXCR4 results in failure
      to release mature neutrophils from bone marrow. Although blood neutrophil numbers
      in inbred mouse strains and individual human subjects are tightly controlled,
      their large variation among outbred populations suggests genetic factors. One
      example is benign ethnic neutropenia, which is found in some African Americans.
      Reduced and elevated neutrophil counts, even within the normal range, are
      associated with excess all-cause mortality.

PMID- 18832669
TI  - Cutting edge: Inhibition of NF-kappaB-mediated TSLP expression by retinoid X
      receptor.
AB  - The epithelial-derived cytokine thymic stromal lymphopoietin (TSLP) has important
      roles in the initiation of allergic airway inflammation and the activation of
      dendritic cells. We have shown that the human TSLP gene is regulated in a NF
      kappaB-dependent manner; however the factors that negatively regulate TSLP
      expression are not known. In this study we demonstrate that 9-cis-retinoic acid
      (9-cis-RA) is a negative regulator of TSLP expression in airway epithelial cells.
      This inhibition is manifested as a block in the IL-1beta-mediated recruitment of
      NF-kappaB to the human TSLP promoter. 9-cis-RA-mediated inhibition is not
      restricted to TSLP gene expression but rather reflects a general inhibition of NF
      kappaB activation, as other NF-kappaB-regulated-genes were also inhibited in a
      similar manner by 9-cis-RA treatment. Taken as a whole, these data demonstrate
      that inhibition of IL-1beta-dependent genes by active retinoid X receptors
      involves antagonism of NF-kappaB signaling.

PMID- 18832670
TI  - Cutting edge: Autocrine TGF-beta sustains default tolerogenesis by IDO-competent
      dendritic cells.
AB  - CD8(-) and CD8(+) dendritic cells (DCs) are distinct subsets of mouse splenic
      accessory cells with opposite but flexible programs of Ag presentation, leading
      to immunogenic and tolerogenic responses, respectively. In this study, we show
      that the default tolerogenic function of CD8(+) DCs relies on autocrine TGF-beta,
      which sustains the activation of IDO in response to environmental stimuli. CD8(-)
      DCs do not produce TGF-beta, yet externally added TGF-beta induces IDO and turns
      those cells from immunogenic into tolerogenic cells. The acquisition of a
      suppressive phenotype by CD8(-) DCs correlates with activation of the PI3K/Akt
      and noncanonical NF-kappaB pathways. These data are the first to link TGF-beta
      signaling with IDO in controlling spontaneous tolerogenesis by DCs.

PMID- 18832671
TI  - Cutting edge: TLR ligands increase TCR triggering by slowing peptide-MHC class I
      decay rates.
AB  - TLR ligands are among the key stimuli driving the optimal dendritic cell (DC)
      maturation critical for strong and efficacious T cell priming. In this study, we
      show that part of this effect occurs via increased TCR triggering. Pretreatment
      of DCs with TLR ligands resulted in the triggering of many more TCRs in
      responding CD8(+) T cells. Importantly, even when DCs expressed the same amount
      of cognate peptide-MHC (pMHC) molecules, TLR ligand treatment resulted in down
      regulation of larger numbers of TCR molecules. This was independent of the up
      regulation of costimulatory, adhesion or cytokine molecules or the amount of
      noncognate pMHCs. Rather, DCs pretreated with TLR ligands exhibited increased
      stability of cognate pMHCs, enabling extended TCR triggering. These findings are
      of potential importance to T cell vaccination.

PMID- 18832672
TI  - Cutting edge: CD47 controls the in vivo proliferation and homeostasis of
      peripheral CD4+ CD25+ Foxp3+ regulatory T cells that express CD103.
AB  - Peripheral CD103(+)Foxp3(+) regulatory T cells (Tregs) can develop both from
      conventional naive T cells upon cognate Ag delivery under tolerogenic conditions
      and from thymic-derived, expanded/differentiated natural Tregs. We here show that
      CD47 expression, a marker of self on hematopoietic cells, selectively regulated
      CD103(+)Foxp3(+) Treg homeostasis at the steady state. First, the proportion of
      effector/memory-like (CD44(high)CD62L(low)) CD103(+)Foxp3(+) Tregs rapidly
      augmented with age in CD47-deficient mice (CD47(-/-)) as compared with age
      matched control littermates. Yet, the percentage of quiescent
      (CD44(low)CD62L(high)) CD103(-)Foxp3(+) Tregs remained stable. Second, the
      increased proliferation rate (BrdU incorporation) observed within the CD47(-/
      )Foxp3(+) Treg subpopulation was restricted to those Tregs expressing CD103.
      Third, CD47(-/-) Tregs maintained a normal suppressive function in vitro and in
      vivo and their increased proportion in old mice led to a decline of Ag-specific T
      cell responses. Thus, sustained CD47 expression throughout life is critical to
      avoid an excessive expansion of CD103(+) Tregs that may overwhelmingly inhibit Ag
      specific T cell responses.

PMID- 18832673
TI  - Cutting edge: Immunity against a "silent" salivary antigen of the Lyme vector
      Ixodes scapularis impairs its ability to feed.
AB  - Ixodes scapularis ticks transmit the Lyme disease agent in the United States.
      Although strong antitick immunity mediates tick rejection by certain vertebrates,
      only a few Ags have been molecularly characterized. We show that guinea pig
      vaccination against a secreted tick salivary immunomodulator, sialostatin L2, can
      lead to decreased feeding ability of I. scapularis nymphs. Increased rejection
      rate, prolonged feeding time, and apparent signs of inflammation were observed
      for nymphs attached to vaccinated animals, indicating a protective host immune
      response. Interestingly, sialostatin L2 humoral recognition does not take place
      upon repeated tick exposure in control animals, but only in the vaccinated
      animals that neutralize sialostatin L2 action. Therefore, we demonstrate an
      essential sialostatin L2 role upon nymphal infestation that can be blocked by
      vertebrate immunity and propose the discovery of similarly "silent" Ags toward
      the development of a multicomponent vaccine that will protect against tick bites
      and the pathogens they transmit.

PMID- 18832674
TI  - Cutting edge: Contact with secondary lymphoid organs drives postthymic T cell
      maturation.
AB  - T cell development, originally thought to be completed in the thymus, has
      recently been shown to continue for several weeks in the lymphoid periphery. The
      forces that drive this peripheral maturation are unclear. The use of mice
      transgenic for GFP driven by the RAG2 promoter has enabled the ready
      identification and analysis of recent thymic emigrants. Here, we show that recent
      thymic emigrant maturation is a progressive process and is promoted by T cell
      exit from the thymus. Further, we show that this maturation occurs within
      secondary lymphoid organs and does not require extensive lymphocyte
      recirculation.

PMID- 18832675
TI  - Activation of human plasmacytoid dendritic cells by TLR9 impairs Fc gammaRII
      mediated uptake of immune complexes and presentation by MHC class II.
AB  - Human plasmacytoid dendritic cells (pDCs)(2) exploit Ag uptake receptors like
      CD32a for internalization of exogenous Ags. Activation of pDC by TLR9 ligand CpG
      C induces strong maturation. Surprisingly, we observed that CpG-C-stimulated pDCs
      showed impaired Ag-specific T cell proliferation whereas the induction of
      allogeneic T cell proliferation was not affected. We demonstrated that signals
      from TLR9 caused a rapid down-regulation of the capacity of pDC to take-up Ab-Ag
      complexes without altering their CD32a expression, thus explaining the reduced Ag
      presentation. The recent contrasting biological responses that were observed upon
      TLR9 ligation in pDCs prompted us to study the effect of several TLR9 ligands. We
      observed that type I IFN-inducer CpG-A, localizing in the early endosomal
      compartment, did not affect CD32a function, whereas CpGs localizing in the late
      endosomes and inducing pDC maturation clearly inhibited CD32a-mediated Ag uptake
      and presentation. We conclude that TLR9 ligands not only determine the type of
      response, i.e., type I IFN production (innate immunity) or maturation (adaptive
      immunity), but also directly affect Ag presentation capacity of pDCs. We
      hypothesize that pDC, once activated via TLR9-ligands reaching the late
      endosomes, can only present initially sampled Ags and thus are protected from
      uptake and processing of additional potential self-Ags.

PMID- 18832676
TI  - Alterations of the medullary epithelial compartment in the Aire-deficient thymus:
      implications for programs of thymic epithelial differentiation.
AB  - A widely held model of thymic epithelial differentiation is based on patterns of
      keratin expression, where a K8(+)K5(+) progenitor gives rise to K8(+)K5/K14(-)
      cortical thymic epithelium (CTEC), and medullary thymic epithelium (MTEC) are K8(
      )K5(+)K14(+). The thymic phenotype of p63-deficient mice indicates that p63 is an
      important regulator of proximal stages of thymic epithelial differentiation. In
      this study, we have examined several features of the thymic medullary compartment
      in wild-type and Aire-deficient thymi in an effort to integrate the proapoptotic
      activity of Aire with these different perspectives of TE differentiation.
      Patterns of keratin and p63 expression by MTEC described here are difficult to
      reconcile with postmitotic MTEC that express a K8(-)K14(+) phenotype and suggest
      that the patterns of p63 and keratin expression reflecting differentiation
      programs of other epithelial tissues provide a useful framework for revising
      models of TE differentiation. Alterations of the Aire(-/-) MTEC compartment
      included reduced expression of p63, increased frequency of MTEC expressing
      truncated Aire protein, and shifts in the pattern of keratin expression and
      epithelial morphology. These data suggest a scenario where cellular targets of
      Aire-mediated apoptosis are postmitotic MTEC that have not yet completed their
      terminal differentiation program. According to this view, the minor population of
      globular K8(+)K14(-/low) MTEC observed in the Aire(+/+) thymus and significantly
      expanded in the Aire(-/-) thymic medulla represent end-stage, terminally
      differentiated MTEC. These Aire-dependent alterations of the MTEC compartment
      suggest that the activity of Aire is not neutral with respect to the program of
      MTEC differentiation.

PMID- 18832677
TI  - Differential pathways govern CD4+ CD28- T cell proinflammatory and effector
      responses in patients with coronary artery disease.
AB  - Patients with acute coronary syndromes experience circulatory and intraplaque
      expansion of an aggressive and unusual CD4(+) lymphocyte subpopulation lacking
      the CD28 receptor. These CD4(+)CD28(-) cells produce IFN-gamma and perforin, and
      are thought to play an important role in coronary atheromatous plaque
      destabilization. Aberrant expression of killer Ig-like receptors (KIRs) in
      CD4(+)CD28(-) cells is broadly thought to be responsible for their cytotoxicity,
      but the mechanisms involved remain poorly defined. We therefore sought to
      investigate the mechanism and regulation of CD4(+)CD28(-) cell functionality
      using T cell clones (n = 536) established from patients with coronary artery
      disease (n = 12) and healthy volunteers (n = 3). Our functional studies
      demonstrated that KIR2DS2 specifically interacted with MHC class I-presenting
      human heat shock protein 60 (hHSP60) inducing cytotoxicity. Further
      investigations revealed the novel finding that hHSP60 stimulation of TCR alone
      could not induce a cytotoxic response, and that this response was specific and
      KIR dependent. Analysis of CD4(+)CD28(-)2DS2(+) clones (n = 162) showed that not
      all were hHSP60 cytotoxic; albeit, their prevalence correlated with coronary
      disease status (p = 0.017). A higher proportion of clones responded to hHSP60 by
      IFN-gamma compared with perforin (p = 0.008). In this study, for the first time,
      we define the differential regulatory pathways involved in CD4(+)CD28(-) cell
      proinflammatory and effector responses. We describe in this study that, contrary
      to previous reports, CD4(+)CD28(-) cell recognition and killing can be specific
      and discriminate. These results, in addition to contributing to the understanding
      of CD4(+)CD28(-) cell functionality, may have implications for the monitoring and
      management of coronary artery disease progression.

PMID- 18832678
TI  - Thymus exosomes-like particles induce regulatory T cells.
AB  - Exosomes released from different types of cells have been proposed to contribute
      to intercellular communication. We report that thymic exosome-like particles
      (ELPs) released from cells of the thymus can induce the development of Foxp3(+)
      regulatory T (Treg) cells in the lung and liver. Thymic ELPs also induce the
      conversion of thymic CD4(+)CD25(-) T cells into Tregs. Tregs induced by thymic
      ELPs suppress the proliferation of CD4(+)CD25(-) T cells in vitro and in vivo. We
      further show that neutralization of TGF-beta in ELPs partially reverses thymic
      ELP-mediated induction of CD4(+)Foxp3(+) T cells in the lung and liver. This
      study demonstrates that thymic ELPs participate in the induction of Foxp3(+)
      Tregs. Also, TGF-beta of thymic ELPs might be required for the generation of
      Tregs in the peripheral tissues.

PMID- 18832679
TI  - Blimp-1 induced by IL-4 plays a critical role in suppressing IL-2 production in
      activated CD4 T cells.
AB  - Although an inhibitory function of IL-4 in CD4 T cell IL-2 production has long
      been recognized, a mechanism mediating the inhibition remains unclear. In this
      study we demonstrate that IL-4 displays a potent suppressive function in IL-2
      production of activated CD4 T cells through STAT6. IL-4-induced IL-2 suppression
      required IL-2 because IL-2 neutralization restored the production of IL-2 even in
      the presence of IL-4. In vivo, enhanced IL-2 production was found in nematode
      infected IL-4- or STAT6-deficient animals, whereas immunization in the presence
      of IL-4 substantially diminished IL-2 production by Ag-specific CD4 T cells. IL-2
      mRNA expression was reduced when T cells were stimulated in the presence of IL-4,
      whereas IL-2 mRNA decay was unaltered, suggesting that IL-4 mediates the
      suppression at a transcriptional level. Blimp-1 induced by IL-4 stimulation in
      activated CD4 T cells was found to be necessary to mediate the IL-2 inhibition as
      IL-4-mediated IL-2 suppression was less pronounced in activated CD4 T cells
      deficient in Blimp-1. Taken together, our results demonstrate a potential link
      with IL-4, Blimp-1, and IL-2 production, suggesting that Blimp-1 may play an
      important role in controlling IL-2 production in activated T cells and in
      adaptive T cell immunity.

PMID- 18832680
TI  - CD4 T cell-mediated rejection of cardiac allografts in B cell-deficient mice.
AB  - CD4 T cell-dependent mechanisms promoting allograft rejection include expression
      of inflammatory functions within the graft and the provision of help for donor
      reactive CD8 T cell and Ab responses. These studies tested CD4 T cell-mediated
      rejection of MHC-mismatched cardiac allografts in the absence of both CD8 T and B
      lymphocytes. Whereas wild-type C57BL/6 recipients depleted of CD8 T cells
      rejected A/J cardiac grafts within 10 days, allografts were not rejected in B
      cell-deficient B6.muMT(-/-) recipients depleted of CD8 T cells. Isolated wild
      type C57BL/6 and B6.muMT(-/-) CD4 T cells had nearly equivalent in vivo
      alloreactive proliferative responses. CD4 T cell numbers in B6.muMT(-/-) spleens
      were 10% of that in wild-type mice but were only slightly decreased in peripheral
      lymph nodes. CD8 T cell depletion did not abrogate B6.muMT(-/-) mice rejection of
      A/J skin allografts and this rejection rendered these recipients able to reject
      A/J cardiac allografts. Redirection of the alloimmune response to the lymph nodes
      by splenectomy conferred the ability of B6.muMT(-/-) CD4 T cells to reject
      cardiac allografts. These results indicate that the low number of splenic CD4 T
      cells in B6.muMT(-/-) mice underlies the inability to reject cardiac allografts
      and this inability is overcome by diverting the CD4 T cell response to the
      peripheral lymph nodes.

PMID- 18832681
TI  - Splenic phagocytes promote responses to nucleosomes in (NZB x NZW) F1 mice.
AB  - Autoantigen presentation to T cells is crucial for the development of autoimmune
      disease. However, the mechanisms of autoantigen presentation are poorly
      understood. In this study, we show that splenic phagocytes play an important role
      in autoantigen presentation in murine lupus. Nucleosomes are major autoantigens
      in systemic lupus erythematosus. We found that nucleosome-specific T cells were
      stimulated dominantly in the spleen, compared with lymph nodes, lung, and thymus.
      Among splenic APCs, F4/80(+) macrophages and CD11b(+)CD11c(+) dendritic cells
      were strong stimulators for nucleosome-specific T cells. When splenic phagocytes
      were depleted in (NZB x NZW) F(1) (NZB/W F(1)) mice, nucleosome presentation in
      the spleen was dramatically suppressed. Moreover, depletion of splenic phagocytes
      significantly suppressed anti-nucleosome Ab and anti-dsDNA Ab production.
      Proteinuria progression was delayed and survival was prolonged in phagocyte
      depleted mice. The numbers of autoantibody- secreting cells were decreased in the
      spleen from phagocyte-depleted mice. Multiple injections of splenic F4/80(+)
      macrophages, not those of splenic CD11c(+) dendritic cells, induced autoantibody
      production and proteinuria progression in NZB/W F(1) mice. These results indicate
      that autoantigen presentation by splenic phagocytes including macrophages
      significantly contributes to autoantibody production and disease progression in
      lupus-prone mice.

PMID- 18832682
TI  - Maintenance of thymic epithelial phenotype requires extrinsic signals in mouse
      and zebrafish.
AB  - Thymopoiesis strictly depends on proper differentiation of the thymic epithelial
      anlage. Differentiation of thymic epithelial cells (TECs) is controlled by the
      Foxn1 transcription factor. The in vivo signals initiating and maintaining Foxn1
      expression in the future thymus anlage are unknown. In the mouse, bone
      morphogenetic protein (BMP) signaling is required for the maintenance of Foxn1
      expression in TECs, as shown here by lineage tracing using a Foxn1-driven Cre
      transgene. Loss of Foxn1 expression after BMP inhibition reverts TECs to a basal
      state of pharyngeal epithelium unable to support T cell development; it does not
      divert them into a parathyroid fate. In zebrafish larvae, BMP inhibition likewise
      causes loss of foxn1 expression in the thymic anlage and subsequent impairment of
      thymopoiesis. These results indicate an evolutionarily conserved role of BMP
      signaling in the maintenance of Foxn1 expression.

PMID- 18832683
TI  - Spontaneous colitis occurrence in transgenic mice with altered B7-mediated
      costimulation.
AB  - The B7 costimulatory molecules govern many aspects of T cell immune responses by
      interacting with CD28 for costimulation, but also with CTLA-4 for immune
      suppression. Although blockade of CTLA-4 with Ab in humans undergoing cancer
      immune therapy has led to some cases of inflammatory bowel disease, spontaneous
      animal models of colitis that depend upon modulation of B7 interactions have not
      been previously described. In this study, we demonstrate that mice expressing a
      soluble B7-2 Ig Fc chimeric protein spontaneously develop colitis that is
      dependent on CD28-mediated costimulation of CD4(+) T cells. We show that the
      chimeric protein has mixed agonistic/antagonist properties, and that it acts in
      part by blocking the cell intrinsic effects on T cell activation of engagement of
      CTLA-4. Disease occurred in transgenic mice that lack expression of the
      endogenous B7 molecules (B7 double knock-out mice), because of the relatively
      weak costimulatory delivered by the chimeric protein. Surprisingly, colitis was
      more severe in this context, which was associated with the decreased number of
      Foxp3(+) regulatory T cells in transgenic B7 double knock-out mice. This model
      provides an important tool for examining how B7 molecules and their effects on
      CTLA-4 modulate T cell function and the development of inflammatory diseases.

PMID- 18832684
TI  - The exocytosis regulator synaptotagmin V controls phagocytosis in macrophages.
AB  - Synaptotagmins (Syts) play a key role in the regulation of Ca(2+)-triggered
      exocytosis and membrane fusion events, two crucial events associated to the
      phagocytic process. In the present study, we investigated the role of Syt V, a
      regulator of focal exocytosis, in phagocytosis. In macrophages, Syt V is
      localized on recycling endosomes and on filopodia-like structures and is
      recruited to the nascent phagosomes independently of the phagocytic receptor
      engaged. Silencing of Syt V by RNA interference revealed a role for this protein
      for phagocytosis, particularly under conditions of high membrane demand. In
      contrast, silencing of Syt V had no effect on the recruitment of the lysosomal
      marker LAMP1 to phagosomes, indicating that phagosome maturation is not regulated
      by Syt V. Collectively, these results illustrate the importance of Syt V in the
      regulation of an important innate function of macrophages. Furthermore, our
      results are consistent with the concept that focal exocytosis of endocytic
      organelles is a key event in phagocytosis and suggest that Syt V regulates this
      process.

PMID- 18832685
TI  - Priming of a novel subset of CD28+ rapidly expanding high-avidity effector memory
      CTL by post maturation electroporation-CD40L dendritic cells is IL-12 dependent.
AB  - Dendritic cell (DC)-based immunotherapeutics must induce robust CTL capable of
      killing tumor or virally infected cells in vivo. In this study, we show that RNA
      electroporated post maturation and coelectroporated with CD40L mRNA (post
      maturation electroporation (PME)-CD40L DC) generate high-avidity CTL in vitro
      that lyse naturally processed and presented tumor Ag. Unlike cytokine mixture
      matured DC which induce predominantly nonproliferative effector memory CD45RA(+)
      CTL, PME-CD40L DC prime a novel subset of Ag-specific CTL that can be expanded to
      large numbers upon sequential DC stimulation in vitro. We have defined these
      cells as rapidly expanding high-avidity (REHA) CTL based on: 1) the maintenance
      of CD28 expression, 2) production of high levels of IFN-gamma and IL-2 in
      response to Ag, and 3) the demonstration of high-avidity TCR that exhibit strong
      cytolytic activity toward limiting amounts of native Ag. We demonstrate that
      induction of REHA CTL is dependent at least in part on the production of IL-12.
      Interestingly, neutralization of IL-12 did not effect cytolytic activity of REHA
      CTL when Ag is not limiting, but did result in lower TCR avidity of Ag-reactive
      CTL. These results suggest that PME-CD40L DC are uniquely capable of delivering
      the complex array of signals needed to generate stable CD28(+) REHA CTL, which if
      generated in vivo may have significant clinical benefit for the treatment of
      infectious disease and cancer.

PMID- 18832686
TI  - Human memory B lymphocyte subsets fulfill distinct roles in the anti
      polysaccharide and anti-protein immune response.
AB  - There is controversy on the role of IgM memory and switched memory B lymphocytes
      in the Ab response to T cell-independent and T cell-dependent Ags. We
      transplanted SCID/SCID mice with human B lymphocyte subsets and immunized them
      with heat-inactivated Streptococcus pneumoniae or with a pneumococcal vaccine.
      Inactivated S. pneumoniae and soluble pneumococcal capsular polysaccharides
      elicited an IgM anti-polysaccharide and anti-protein Ab response from IgM memory
      B lymphocytes and an IgG anti-polysaccharide and anti-protein response from
      switched memory B lymphocytes. In addition to the IgM Ab response, IgM memory B
      cells elicited an IgG anti-polysaccharide and anti-protein Ab response after
      immunization with inactivated S. pneumoniae or soluble pneumococcal capsular
      polysaccharides. In conclusion, our findings provide evidence for a versatile
      role of IgM memory B cells in T-independent and T-dependent immune responses.

PMID- 18832688
TI  - IFN-gamma-dependent recruitment of mature CD27(high) NK cells to lymph nodes
      primed by dendritic cells.
AB  - NK cells have been proposed to be an initial source of IFN-gamma that supports
      either Th1 or CTL priming. Although NK cells reside in naive lymph nodes (LN) at
      a very low frequency, they can be recruited into LN draining sites of infection,
      inflammation, or immunization where they potentially influence adaptive immunity.
      In this study, we report that mature CD27(high) NK cells are predominantly
      recruited into the draining LN following dendritic cell (DC) challenge.
      Importantly, the recruitment of the CD27(high) NK cell subset in the draining LN
      was dependent on host IFN-gamma and the activation status of NK cells. Endogenous
      epidermal DC migration induced by hapten challenge also triggers NK cell
      recruitment to the draining LN in an IFN-gamma-dependent mechanism. Thus, our
      results identify that CD27(high) NK cells are the dominant population recruited
      to the draining LN and NK cell recruitment requires endogenous IFN-gamma in
      coordinating with DC migration.

PMID- 18832687
TI  - PD-1-dependent mechanisms maintain peripheral tolerance of donor-reactive CD8+ T
      cells to transplanted tissue.
AB  - Peripheral mechanisms of self-tolerance often depend on the quiescent state of
      the immune system. To what degree such mechanisms can be engaged in the
      enhancement of allograft survival is unclear. To examine the role of the PD-1
      pathway in the maintenance of graft survival following blockade of costimulatory
      pathways, we used a single-Ag mismatch model of graft rejection where we could
      track the donor-specific cells as they developed endogenously and emerged from
      the thymus. We found that graft-specific T cells arising under physiologic
      developmental conditions at low frequency were actively deleted at the time of
      transplantation under combined CD28/CD40L blockade. However, this deletion was
      incomplete, and donor-specific cells that failed to undergo deletion up-regulated
      expression of PD-1. Furthermore, blockade of PD-1 signaling on these cells via in
      vivo treatment with anti-PD-1 mAb resulted in rapid expansion of donor-specific T
      cells and graft loss. These results suggest that the PD-1 pathway was engaged in
      the continued regulation of the low-frequency graft-specific immune response and
      thus in maintenance of graft survival.

PMID- 18832689
TI  - Casitas B-lineage lymphoma b inhibits antigen recognition and slows cell cycle
      progression at late times during CD4+ T cell clonal expansion.
AB  - Optimal clonal expansion of CD4(+) T cells during the primary response to Ag
      requires prolonged TCR recognition of peptide Ag/MHC complexes. In this study, we
      investigated the capacity of Casitas B-lineage lymphoma b (Cbl-b) to counter
      regulate late TCR signals necessary for continued cell division in vivo. During
      the first 24 h of a primary response to Ag, Cblb(-/-) 5C.C7 CD4(+) T cells
      demonstrated no alteration in CD69, CD25, and CD71 up-regulation or cell growth
      as compared with wild-type cells. Nevertheless, beyond 24 h, both the expression
      of CD71 and the rate of cell division were increased in the genetic absence of
      Cbl-b, leading to an augmented clonal expansion. This deregulation of late T cell
      proliferation in the absence of Cbl-b resulted in part from an inability of Cblb(
      /-) T cells to desensitize Akt, PLCgamma-1, and ERK phosphorylation events
      downstream of the TCR/CD3 complex, in addition to their failure to undergo a
      growth arrest in the absence of Ag. These observations now suggest a novel role
      for Cbl-b in triggering the exit from cell cycle at the end of a CD4(+) T cell
      clonal expansion.

PMID- 18832690
TI  - Imidazoquinoline acts as immune adjuvant for functional alteration of thymic
      stromal lymphopoietin-mediated allergic T cell response.
AB  - Atopic dermatitis is a major allergic disease that develops through dysregulation
      of Th2-mediated inflammation. Although dendritic cells (DCs) have been thought to
      play a critical role in the upstream phase of the allergic cascade, conventional
      drugs such as steroids and chemical mediator antagonists target the effector
      cells or factors in allergic inflammation. Recently, it has been demonstrated
      that interaction between thymic stromal lymphopoietin (TSLP) and human DCs plays
      an essential role in evoking inflammatory Th2 responses in allergy through OX40
      ligand expression on DCs. In this study, we provide evidence that R848, an
      imidazoquinoline compound, which is a TLR ligand and a strong Th1 response
      inducing reagent, is a potent adjuvant for the alteration of the Th2-inducing
      potency of human DCs activated by TSLP (TSLP-DCs). R848 inhibited the
      inflammatory Th2-inducing capacity of TSLP-DCs and redirected them to possessing
      an IL-10 and IFN-gamma-producing regulatory Th1-inducing capacity. This
      functional alteration depended on both repression of OX40 ligand expression and
      induction of IL-12 production from DCs by the addition of R848. Additionally,
      R848 had the ability to inhibit the TSLP-mediated expansion and maintenance of
      the Th2 memory response. These findings suggest that imidazoquinoline may be a
      useful in the treatment of allergic diseases that are triggered by TSLP.

PMID- 18832691
TI  - Activation of human peripheral IgM+ B cells is transiently inhibited by BCR
      independent aggregation of Fc gammaRIIB.
AB  - Immune complexes can trigger a SHIP-1-independent proapoptotic signal in mouse
      class-switched IgG(+) B cells and plasma cells by binding to Fc gammaRIIB, in the
      absence of concomitant coaggregation with BCR, hence regulating plasma cell
      survival and participating in the selection of B cells producing high affinity
      Abs during secondary Ab responses. By contrast, we demonstrate in the present
      study that the unique aggregation of Fc gammaRIIB on human peripheral IgM(+) B
      cells does not induce apoptosis but transiently inhibits B cell proliferation and
      calcium influx triggered by BCR cross-linking. Using human peripheral B cells and
      IIA1.6 lymphoma B cells expressing wild-type human Fc gammaRIIB (IIA1.6-Fc
      gammaRIIB), we also show that the unique aggregation of human Fc gammaRIIB
      induces ITIM phosphorylation. This aggregation provokes the recruitment of
      phosphorylated SHIP-1 by Fc gammaRIIB and inhibits the constitutive
      phosphorylation of Akt in human IIA1.6-Fc gammaRIIB cells. This inhibitory
      signaling pathway is abrogated in IIA1.6 cells expressing ITIM-mutated Fc
      gammaRIIB (Fc gammaRIIB(Y292G)), suggesting that ITIM phosphorylation is
      necessary for Fc gammaRIIB-induced B cell blockade. Overall, we demonstrate that
      the unique aggregation of Fc gammaRIIB on human peripheral IgM(+) B cells is
      sufficient to transiently down-regulate their activation without inducing
      apoptosis. Our results suggest that Fc gammaRIIB could negatively regulate IgM(+)
      B cells before class-switch occurrence and that its unique engagement by immune
      complexes represents a reversible checkpoint for peripheral IgM(+) B cells.

PMID- 18832692
TI  - Cyclooxygenase inhibition during allergic sensitization increases STAT6
      independent primary and memory Th2 responses.
AB  - Immune sensitization and memory generation are required for the development of
      allergic inflammation. Our previous studies demonstrate that the cyclooxygenase
      (COX) metabolic pathway is actively involved in allergic responses and COX
      inhibition increases allergic airway inflammation in a STAT6-independent fashion.
      To test the hypothesis that COX inhibition augments allergic inflammation by
      enhancing immune sensitization and memory, we sensitized STAT6 knockout mice with
      an i.p. injection of OVA with aluminum hydroxide as an adjuvant and treated the
      mice with the COX inhibitor indomethacin or vehicle for analyses of the primary
      and memory immune responses. We found that COX inhibition during immune
      sensitization, but not the allergic challenge phase, was necessary and sufficient
      to increase allergic inflammation. COX inhibition during sensitization increased
      the numbers of mature dendritic cells and activated CD4 T cells in the spleen and
      augmented OVA-specific IL-5 and IL-13 responses of the splenic CD4 T cells at day
      5 after sensitization. COX inhibition during sensitization also augmented
      allergic Th2 response to OVA challenge 90 days after the sensitization.
      Therefore, COX inhibition during allergic sensitization augments allergic
      responses by enhancing Th2 cell activation and memory generation and the
      proallergic effect is STAT6-independent. These findings provide a mechanistic
      explanation for the increased allergic inflammation previously shown in the mice
      treated with COX inhibitors and in COX-deficient mice and suggest that use of COX
      inhibiting drugs during initial allergen exposure may increase the risk of
      developing allergic responses.

PMID- 18832693
TI  - c-FLIP protects mature T lymphocytes from TCR-mediated killing.
AB  - Although c-FLIP has been identified as an important player in the extrinsic
      (death receptor-induced) apoptosis pathway, its endogenous function in mature T
      lymphocytes remains undefined. c-FLIP may inhibit or promote T cell death as
      previous data demonstrate that the c-FLIP(L) isoform can promote or inhibit
      caspase 8 activation while the c-FLIP(S) isoform promotes or inhibits T cell
      death when overexpressed. Although the c-FLIP(R) isoform inhibits cell death in
      cell lines, its function in T cells remains unknown. To investigate the function
      of c-FLIP in mature T cells, we have generated several genetic mouse models with
      c-FLIP or its individual isoforms deleted in mature T cells. Surprisingly, we
      found that c-FLIP protects mature T cells not only from apoptosis induced by the
      death receptors Fas and TNFR but also from TCR-mediated and spontaneous
      apoptosis. Thus, c-FLIP plays an essential role in protecting mature T cells from
      a death signal induced through the TCR itself and is required for naive T cell
      survival. Our results demonstrate that c-FLIP functions beyond the extrinsic
      death pathway.

PMID- 18832694
TI  - Normal development and activation but altered cytokine production of Fyn
      deficient CD4+ T cells.
AB  - The Src family kinase Fyn is expressed in T cells and has been shown to
      phosphorylate proteins involved in TCR signaling, cytoskeletal reorganization,
      and IL-4 production. Fyn-deficient mice have greatly decreased numbers of NKT
      cells and have thymocytes and T cells with compromised responses following Ab
      crosslinking of their TCRs. Herein we have addressed the role of Fyn in
      peptide/MHC class II-induced CD4(+) T cell responses. In Fyn-deficient mice,
      CD4(+) T cells expressing the DO11.10 TCR transgene developed normally, and the
      number and phenotype of naive and regulatory DO11.10(+)CD4(+) T cells in the
      periphery were comparable with their wild-type counterparts. Conjugation with
      chicken OVA peptide 323-339-loaded APCs, and the subsequent proliferation in
      vitro or in vivo of DO11.10(+) Fyn-deficient CD4(+) T cells, was virtually
      indistinguishable from the response of DO11.10(+) wild-type CD4(+) T cells.
      Proliferation of Fyn-deficient T cells was not more dependent on costimulation
      through CD28. Additionally, we have found that differentiation, in vitro or in
      vivo, of transgenic CD4(+) Fyn-deficient T cells into IL-4-secreting effector
      cells was unimpaired, and under certain conditions DO11.10(+) Fyn-deficient
      CD4(+) T cells were more potent cytokine-producing cells than DO11.10(+) wild
      type CD4(+) T cells. These data demonstrate that ablation of Fyn expression does
      not alter most Ag-driven CD4(+) T cell responses, with the exception of cytokine
      production, which under some circumstances is enhanced in Fyn-deficient CD4(+) T
      cells.

PMID- 18832695
TI  - XCL1 enhances regulatory activities of CD4+ CD25(high) CD127(low/-) T cells in
      human allergic asthma.
AB  - Chemokine-mediated recruitment of regulatory cell subsets to the airway during
      inflammation and enhancement of their activities are potential strategies for
      therapeutic development in allergic asthma (AA). In this study, we aim to explore
      the role of XCL1, a chemokine associated with immune suppression and allergy, on
      CD4(+)CD25(high)CD127(low/-) regulatory T cell (Treg) function in AA. Flow
      cytometry and PCR analysis showed a reduction in XCL1 and XCR1 expression in AA
      Treg compared with healthy control and nonallergic asthmatic counterparts. This
      reduction in XCL1 expression was associated with the suboptimal regulatory
      function of Treg in AA. Interestingly, incubation with recombinant human XCL1
      significantly increased Treg-mediated suppression and cytotoxicity by up
      regulating expression of XCL1 and chief effector molecules of Treg function.
      Altogether, these results suggest an association between dysregulated XCL1
      expression and reduced Treg activities in AA, as well as a potential role of XCL1
      in reversing defective Treg function in the disease.

PMID- 18832696
TI  - The indoleamine 2,3-dioxygenase pathway is essential for human plasmacytoid
      dendritic cell-induced adaptive T regulatory cell generation.
AB  - Human plasmacytoid dendritic cells (PDCs) can drive naive, allogeneic CD4(+)CD25(
      ) T cells to differentiate into CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs).
      However, the intracellular mechanism or mechanisms underlying PDC-induced Treg
      generation are unknown. In this study, we show that human PDCs express high
      levels of IDO, an intracellular enzyme that catabolizes tryptophan degradation.
      Triggering of TLR 9 with CpG oligodeoxynucleotides activates PDCs to up-regulate
      surface expression of B7 ligands and HLA-DR Ag, but also significantly increases
      the expression of IDO and results in the generation of inducible Tregs from
      CD4(+)CD25(-) T cells with potent suppressor cell function. Blocking IDO activity
      with the pharmacologic inhibitor 1-methyl-D-tryptophan significantly abrogates
      PDC-driven inducible Treg generation and suppressor cell function. Adding
      kynurenine, the immediate downstream metabolite of tryptophan, bypasses the 1
      methyl-D-tryptophan effect and restores PDC-driven Treg generation. Our results
      demonstrate that the IDO pathway is essential for PDC-driven Treg generation from
      CD4(+)CD25(-) T cells and implicate the generation of kynurenine pathway
      metabolites as the critical mediator of this process.

PMID- 18832697
TI  - Glucocorticoid-induced TNF receptor expression by T cells is reciprocally
      regulated by NF-kappaB and NFAT.
AB  - Although the transcription factor Foxp3 is implicated in regulating
      glucocorticoid-induced TNF receptor (GITR) expression in the T regulatory cell
      lineage, little is known about how GITR is transcriptionally regulated in
      conventional T cells. In this study, we provide evidence that TCR-mediated GITR
      expression depends on the ligand affinity and the maturity of conventional T
      cells. A genetic dissection of GITR transcriptional control revealed that of the
      three transcription factors downstream of the classical NF-kappaB pathway (RelA,
      cRel, and NF-kappaB1), RelA is a critical positive regulator of GITR expression,
      although cRel and NF-kappaB1 also play a positive regulatory role. Consistent
      with this finding, inhibiting NF-kappaB using Bay11-7082 reduces GITR up
      regulation. In contrast, NFAT acts as a negative regulator of GITR expression.
      This was evidenced by our findings that agents suppressing NFAT activity (e.g.,
      cyclosporin A and FK506) enhanced TCR-mediated GITR expression, whereas agents
      enhancing NFAT activity (e.g., lithium chloride) suppressed TCR-mediated GITR up
      regulation. Critically, the induction of GITR was found to confer protection to
      conventional T cells from TCR-mediated apoptosis. We propose therefore that two
      major transcriptional factors activated downstream of the TCR, namely, NF-kappaB
      and NFAT, act reciprocally to balance TCR-mediated GITR expression in
      conventional T cells, an outcome that appears to influence cell survival.

PMID- 18832698
TI  - Positive and negative regulation of high affinity IgE receptor signaling by Src
      homology region 2 domain-containing phosphatase 1.
AB  - Src homology region 2 domain-containing phosphatase 1 (SHP-1), a cytoplasmic
      protein tyrosine phosphatase, plays an important role for the regulation of
      signaling from various hematopoietic cell receptors. Although SHP-1 is shown to
      be a negative signal modulator in mast cells, its precise molecular mechanisms
      are not well defined. To elucidate how SHP-1 regulates mast cell signaling, we
      established bone marrow-derived mast cells from SHP-1-deficient motheaten and
      wild-type mice and analyzed downstream signals induced by cross-linking of high
      affinity IgE receptor, Fc epsilonRI. Upon Fc epsilonRI ligation, motheaten
      derived bone marrow-derived mast cells showed enhanced tyrosine phosphorylation
      of Src homology region 2 domain-containing leukocyte protein of 76 kDa (SLP-76)
      and linker for activation of T cells, activation of mitogen-activated protein
      kinases and gene transcription and production of cytokine. Because the activity
      of Syk, responsible for the phosphorylation of SLP-76 and linker for activation
      of T cells, is comparable irrespective of SHP-1, both molecules might be
      substrates of SHP-1 in mast cells. Interestingly, the absence of SHP-1 expression
      disrupted the association between SLP-76 and phospholipase Cgamma, which resulted
      in the decreased phospholipase Cgamma phosphorylation, calcium mobilization, and
      degranulation. Collectively, these results suggest that SHP-1 regulates Fc
      epsilonRI-induced downstream signaling events both negatively and positively by
      functioning as a protein tyrosine phosphatase and as an adaptor protein
      contributing to the formation of signaling complex, respectively.

PMID- 18832699
TI  - Astrocytic regulation of human monocytic/microglial activation.
AB  - Recent reports have described reduced immunological responsiveness and
      stimulatory capacity among monocytes/microglia that infiltrate malignant human
      gliomas. Herein, we demonstrate that culture of ex vivo human monocytes or
      primary human microglia with tumor cells isolated from glioblastoma multiforme
      (GBM) specimens renders them tolerogenic, capable of suppressing the function of
      ex vivo monocytes in the absence of tumor cells or their soluble factors. We
      demonstrate that the tolerance induced in monocytes/microglia by GBM tumor cells
      is not associated with interference with the signaling cascade associated with
      TLR- or CD40-induced monocyte activation. Rather, these tumor cells appear to up
      regulate pathways that antagonize positive signaling pathways, including but not
      limited to STAT3 and STAT5. Finally, we demonstrate that the tolerogenic
      properties of GBM tumor cells amplify properties inherent to nontransformed
      astrocytes. Future studies that identify all of the molecular mechanisms by which
      astrocytes and malignant gliomas suppress monocyte/microglial function will have
      dual therapeutic benefits: suppressing these pathways may benefit patients with
      astrocytic tumors, while enhancing them may benefit patients with autoimmune
      processes within the CNS, such as multiple sclerosis.

PMID- 18832700
TI  - Endoplasmic reticulum stress regulator XBP-1 contributes to effector CD8+ T cell
      differentiation during acute infection.
AB  - The transcription factor X-box-binding protein-1 (XBP-1) plays an essential role
      in activating the unfolded protein response in the endoplasmic reticulum (ER).
      Transcribed XBP-1 mRNA is converted to its active form by unconventional
      cytoplasmic splicing mediated by inositol-requiring enzyme-1 (IRE-1) upon ER
      stress. We report activation of the IRE-1/XBP-1 pathway in effector CD8(+) T
      cells during the response to acute infection. Transcription of unspliced XBP-1
      mRNA is up-regulated by IL-2 signals, while its splicing is induced after TCR
      ligation. Splicing of XBP-1 mRNA was evident during the expansion of Ag-specific
      CD8(+) T cells in response to viral or bacterial infection. An XBP-1 splicing
      reporter revealed that splicing activity was enriched in terminal effector cells
      expressing high levels of killer cell lectin-like receptor G1 (KLRG1).
      Overexpression of the spliced form of XBP-1 in CD8(+) T cells enhanced KLRG1
      expression during infection, whereas XBP-1(-/-) CD8(+) T cells or cells
      expressing a dominant-negative form of XBP-1 showed a decreased proportion of
      KLRG1(high) effector cells. These results suggest that, in the response to
      pathogen, activation of ER stress sensors and XBP-1 splicing contribute to the
      differentiation of end-stage effector CD8(+) T cells.

PMID- 18832701
TI  - HLA-E: strong association with beta2-microglobulin and surface expression in the
      absence of HLA class I signal sequence-derived peptides.
AB  - The nonclassical class I HLA-E molecule folds in the presence of peptide ligands
      donated by the signal sequences of permissive class I HLA alleles, with the aid
      of TAP and tapasin. To identify HLA-E-specific Abs, four monoclonals of the
      previously described MEM series were screened by isoelectric focusing (IEF) blot
      and immunoprecipitation/IEF on >30 single-allele class I transfectants and HLA
      homozygous B lymphoid cells coexpressing HLA-E and HLA-A, -B, -C, -F, or -G.
      Despite their HLA-E-restricted reactivity patterns (MEM-E/02 in IEF blot; MEM
      E/07 and MEM-E/08 in immunoprecipitation), all of the MEM Abs unexpectedly
      reacted with beta(2)-microglobulin (beta(2)m)-free and denatured (but not
      beta(2)m-associated and folded) HLA-E H chains. Remarkably, other HLA-E
      restricted Abs were also reactive with free H chains. Immunodepletion, in vitro
      assembly, flow cytometry, and three distinct surface-labeling methods, including
      a modified (conformation-independent) biotin-labeling assay, revealed the
      coexistence of HLA-E conformers with unusual and drastically antithetic features.
      MEM-reactive conformers were thermally unstable and poorly surface expressed, as
      expected, whereas beta(2)m-associated conformers were either unstable and weakly
      reactive with the prototypic conformational Ab W6/32, or exceptionally stable and
      strongly reactive with Abs to beta(2)m even in cells lacking permissive alleles
      (721.221), TAP (T2), or tapasin (721.220). Noncanonical, immature
      (endoglycosidase H-sensitive) HLA-E glycoforms were surface expressed in these
      cells, whereas mature glycoforms were exclusively expressed (and at much lower
      levels) in cells carrying permissive alleles. Thus, HLA-E is a good, and not a
      poor, beta(2)m assembler, and TAP/tapasin-assisted ligand donation is only one,
      and possibly not even the major, pathway leading to its stabilization and surface
      expression.

PMID- 18832702
TI  - Complexes of two cohorts of CLIP peptides and HLA-DQ2 of the autoimmune DR3-DQ2
      haplotype are poor substrates for HLA-DM.
AB  - Atypical invariant chain (Ii) CLIP fragments (CLIP2) have been found in
      association with HLA-DQ2 (DQ2) purified from cell lysates. We mapped the binding
      register of CLIP2 (Ii 96-104) to DQ2 and found proline at the P1 position, in
      contrast to the canonical CLIP1 (Ii 83-101) register with methionine at P1.
      CLIP1/2 peptides are the predominant peptide species, even for DQ2 from HLA-DM
      (DM)-expressing cells. We hypothesized that DQ2-CLIP1/2 might be poor substrates
      for DM. We measured DM-mediated exchange of CLIP and other peptides for high
      affinity indicator peptides and found it is inefficient for DQ2. DM-DQ-binding
      and DM chaperone effects on conformation and levels of DQ are also reduced for
      DQ2, compared with DQ1. We suggest that the unusual interaction of DQ2 with Ii
      and DM may provide a basis for the known disease associations of DQ2.

PMID- 18832703
TI  - Different development of myelin basic protein agonist- and antagonist-specific
      human TCR transgenic T cells in the thymus and periphery.
AB  - Myelin basic protein (MBP)-specific T cells are thought to play a role in the
      development of multiple sclerosis. MBP residues 111-129 compose an immunodominant
      epitope cluster restricted by HLA-DRB1*0401. The sequence of residues 111-129 of
      MBP (MBP(111-129)) differs in humans (MBP122:Arg) and mice (MBP122:Lys) at aa
      122. We previously found that approximately 50% of human MBP(111-129)
      (MBP122:Arg)-specific T cell clones, including MS2-3C8 can proliferate in
      response to mouse MBP(111-129) (MBP122:Lys). However, the other half of T cell
      clones, including HD4-1C2, cannot proliferate in response to MBP(111-129)
      (MBP122:Lys). We found that MBP(111-129) (MBP122:Lys) is an antagonist for HD4
      1C2 TCR, therefore, MS2-3C8 and HD4-1C2 TCRs are agonist- and antagonist-specific
      TCRs in mice, respectively. Therefore, we examined the development of HD4-1C2 TCR
      and MS2-3C8 TCR transgenic (Tg) T cells in the thymus and periphery. We found
      that dual TCR expression exclusively facilitates the development of MBP(111-129)
      TCR Tg T cells in the periphery of HD4-1C2 TCR/HLA-DRB1*0401 Tg mice although it
      is not required for their development in the thymus. We also found that MS2-3C8
      TCR Tg CD8(+) T cells develop along with MS2-3C8 TCR Tg CD4(+) T cells, and that
      dual TCR expression was crucial for the development of MS2-3C8 TCR Tg CD4(+) and
      CD8(+) T cells in the thymus and periphery, respectively. These results suggest
      that thymic and peripheral development of MBP-specific T cells are different;
      however, dual TCR expression can facilitate their development.

PMID- 18832704
TI  - Uncoupling the roles of HLA-DRB1 and HLA-DRB5 genes in multiple sclerosis.
AB  - Genetic susceptibility to multiple sclerosis (MS) is associated with the MHC
      located on chromosome 6p21. This signal maps primarily to a 1-Mb region
      encompassing the HLA class II loci, and it segregates often with the HLA
      DQB1*0602, -DQA1*0102, -DRB1*1501, -DRB5*0101 haplotype. However, the
      identification of the true predisposing gene or genes within the susceptibility
      haplotype has been handicapped by the strong linkage disequilibrium across the
      locus. African Americans have greater MHC haplotypic diversity and distinct
      patterns of linkage disequilibrium, which make this population particularly
      informative for fine mapping efforts. The purpose of this study was to establish
      the telomeric boundary of the HLA class II region affecting susceptibility to MS
      by assessing genetic association with the neighboring HLA-DRB5 gene as well as
      seven telomeric single nucleotide polymorphisms in a large, well-characterized
      African American dataset. Rare DRB5*null individuals were previously described in
      African populations. Although significant associations with both HLA-DRB1 and HLA
      DRB5 loci were present, HLA-DRB1*1503 was associated with MS in the absence of
      HLA-DRB5, providing evidence for HLA-DRB1 as the primary susceptibility gene.
      Interestingly, the HLA-DRB5*null subjects appear to be at increased risk for
      developing secondary progressive MS. Thus, HLA-DRB5 attenuates MS severity, a
      finding consistent with HLA-DRB5's proposed role as a modifier in experimental
      autoimmune encephalomyelitis. Additionally, conditional haplotype analysis
      revealed a susceptibility signal at the class III AGER locus independent of DRB1.
      The data underscore the power of the African American MS dataset to identify
      disease genes by association in a region of high linkage disequilibrium.

PMID- 18832705
TI  - NKG2D is critical for NK cell activation in host defense against Pseudomonas
      aeruginosa respiratory infection.
AB  - Pseudomonas aeruginosa is a major cause of nosocomial respiratory infections. The
      eradication of P. aeruginosa from the lung involves the orchestrated actions of
      the pulmonary epithelium and both resident and recruited immune cells. The NKG2D
      receptor is constitutively expressed on the surface of circulating and tissue
      resident NK cells (and other cytotoxic lymphocytes), and is capable of
      controlling NK cell activation and production of cytokines, such as IFN-gamma via
      interactions with ligands expressed on the surface of stressed cells. Previously,
      we demonstrated that NKG2D mediates pulmonary clearance of P. aeruginosa. In the
      present study, we investigated the cellular and molecular mechanisms of NKG2D
      mediated clearance of P. aeruginosa using a novel transgenic mouse model of
      doxycycline-inducible conditional expression of NKG2D ligands (retinoic acid
      early transcript 1, alpha) in pulmonary epithelial cells. NKG2D ligand expression
      in this model increased pulmonary clearance, cellular phagocytosis, and survival
      following P. aeruginosa respiratory infection. Additionally, NK cell sensitivity
      to ex vivo LPS stimulation was greater in lung cells isolated from naive
      transgenic mice administered doxycycline. We also showed that NK cells are the
      primary source of lymphocyte-derived IFN-gamma in response to P. aeruginosa
      respiratory infection. Significantly, we demonstrated that NKG2D is critical to
      the nonredundant IFN-gamma production by pulmonary NK cells following acute P.
      aeruginosa infection. These results represent the principal report of NKG2D
      mediated activation of lung NK cells following respiratory infection with an
      opportunistic pathogen and further establish the importance of NKG2D in the host
      response against P. aeruginosa respiratory infection.

PMID- 18832706
TI  - T cell responses to whole SARS coronavirus in humans.
AB  - Effective vaccines should confer long-term protection against future outbreaks of
      severe acute respiratory syndrome (SARS) caused by a novel zoonotic coronavirus
      (SARS-CoV) with unknown animal reservoirs. We conducted a cohort study examining
      multiple parameters of immune responses to SARS-CoV infection, aiming to identify
      the immune correlates of protection. We used a matrix of overlapping peptides
      spanning whole SARS-CoV proteome to determine T cell responses from 128 SARS
      convalescent samples by ex vivo IFN-gamma ELISPOT assays. Approximately 50% of
      convalescent SARS patients were positive for T cell responses, and 90% possessed
      strongly neutralizing Abs. Fifty-five novel T cell epitopes were identified, with
      spike protein dominating total T cell responses. CD8(+) T cell responses were
      more frequent and of a greater magnitude than CD4(+) T cell responses (p <
      0.001). Polychromatic cytometry analysis indicated that the virus-specific T
      cells from the severe group tended to be a central memory phenotype
      (CD27(+)/CD45RO(+)) with a significantly higher frequency of polyfunctional
      CD4(+) T cells producing IFN-gamma, TNF-alpha, and IL-2, and CD8(+) T cells
      producing IFN-gamma, TNF-alpha, and CD107a (degranulation), as compared with the
      mild-moderate group. Strong T cell responses correlated significantly (p < 0.05)
      with higher neutralizing Ab. The serum cytokine profile during acute infection
      indicated a significant elevation of innate immune responses. Increased Th2
      cytokines were observed in patients with fatal infection. Our study provides a
      roadmap for the immunogenicity of SARS-CoV and types of immune responses that may
      be responsible for the virus clearance, and should serve as a benchmark for SARS
      CoV vaccine design and evaluation.

PMID- 18832707
TI  - Rap1 activation is required for Fc gamma receptor-dependent phagocytosis.
AB  - Phagocytosis of IgG-opsonized microbes via the Fc gamma receptor (Fc gammaR)
      requires the precise coordination of a number of signaling molecules, including
      the low-molecular mass GTPases. Little is known about the Ras-family GTPase Rap1
      in this process. We therefore investigated its importance in mediating Fc gammaR
      dependent phagocytosis in NR8383 rat alveolar macrophages. Pulldown of active
      Rap1 and fluorescence microscopic analysis of GFP-RalGDS (Ral guanine
      dissociation stimulator)-transfected macrophages revealed that Rap1 is indeed
      activated by Fc gammaR crosslinking. Inhibition of Rap1 activity, both by Rap1GAP
      (GTPase-activating protein) expression and liposome-delivered blocking Ab,
      severely impaired the ability of cells to ingest IgG-opsonized targets. Fc gammaR
      induced Rap1 activation was found to be independent of both cAMP and Ca(2+),
      suggesting a role for the second messenger-independent guanosine exchange factor,
      C3G. This was supported by the facts that 1) liposome-delivered blocking Ab
      against C3G inhibited both Fc gammaR-dependent phagocytosis and Rap1 activation,
      and 2) both active Rap1GTP and C3G were found to translocate to the phagosome.
      Taken together, our data demonstrate a novel role for Rap1 and its exchange
      factor C3G in mediating Fc gammaR-dependent phagocytosis.

PMID- 18832708
TI  - The efficacy of T cell-mediated immune responses is reduced by the envelope
      protein of the chimeric HIV-1/SIV-KB9 virus in vivo.
AB  - Gp120 is a critical component of the envelope of HIV-1. Its role in viral entry
      is well described. In view of its position on the viral envelope, gp120 is a part
      of the retrovirus that immune cells encounter first and has the potential to
      influence antiretroviral immune responses. We propose that high levels of gp120
      are present in tissues and may contribute to the failure of the immune system to
      fully control and ultimately clear the virus. Herein, we show for the first time
      that lymphoid tissues from acutely HIV-1/SIV (SHIV)-KB9-infected macaques contain
      deposits of gp120 at concentrations that are high enough to induce suppressive
      effects on T cells, thus negatively regulating the antiviral CTL response and
      contributing to virus survival and persistence. We also demonstrate that SHIV-KB9
      gp120 influences functional T cell responses during SHIV infection in a manner
      that suppresses degranulation and cytokine secretion by CTLs. Finally, we show
      that regulatory T cells accumulate in lymphoid tissues during acute infection and
      that they respond to gp120 by producing TGFbeta, a known suppressant of cytotoxic
      T cell activity. These findings have significant implications for our
      understanding of the contribution of non-entry-related functions of HIV-1 gp120
      to the pathogenesis of HIV/AIDS.

PMID- 18832709
TI  - The clathrin-mediated endocytic pathway participates in dsRNA-induced IFN-beta
      production.
AB  - TLR3 and cytoplasmic RIG-I-like receptor (RLR) recognize virus-derived dsRNA and
      induce type I IFN production in a distinct manner. Human TLR3 localizes to the
      endosomal compartments in myeloid dendritic cells (mDCs), while it localizes to
      both the cell surface and interior in fibroblasts and epithelial cells. TLR3
      signaling arises in the intracellular compartment in both cell types and requires
      endosomal maturation. The mechanisms by which extracellular dsRNA is delivered to
      the TLR3-containing organelle remain largely unknown. Among various synthetic
      dsRNAs, poly(I:C) is preferentially internalized and activates TLR3 in mDCs. In
      vitro transcribed dsRNAs hardly induce IFN-beta production in mDCs. In this
      study, we demonstrate that the clathrin-dependent endocytic pathway mediates cell
      entry of poly(I:C) to induce IFN-beta gene transcription. Furthermore, poly(I:C)
      induced IFN-beta production is inhibited by pretreatment of cells with B- and C
      type oligodeoxynucleotides (ODNs) but not with TLR7/8 ligands. The binding and
      internalization of B-type ODNs by mDCs was reduced in the presence of poly(I:C),
      suggesting that poly(I:C) shares the uptake receptor with B- and C-type ODNs.
      Hence, foreign dsRNA is recognized by differently categorized receptors,
      cytoplasmic RIG-I-like receptor, membrane-bound TLR3 and cell-surface RNA
      capture. The endocytic pathway is critical for dsRNA-induced TLR3-mediated cell
      activation.

PMID- 18832710
TI  - Inhibition of IFN-gamma-induced STAT1 tyrosine phosphorylation by human CMV is
      mediated by SHP2.
AB  - Human CMV (HCMV) is a ubiquitous beta-herpesvirus which has developed several
      mechanisms of escape from the immune system. IFN-gamma-induced signaling relies
      on the integrity of the JAK/STAT pathway which is regulated by phosphorylation
      steps and leads to nuclear translocation of tyrosine-phosphorylated STAT1 (STAT1
      P-Tyr), and its binding to IFN-gamma activation site sequences of IFN-gamma
      inducible promoters. Activation of those promoters leads to the expression of
      genes involved in the immune response and in the antiviral effects of IFN-gamma.
      Src homology region 2 domain-containing phosphatase 2 (SHP2) is a ubiquitous
      phosphatase involved in the regulation of IFN-gamma-mediated tyrosine
      phosphorylation. Several mechanisms account for the inhibition IFN-gamma
      signaling pathway by HCMV. In this study, we have identified a new mechanism that
      involved the inhibition of STAT1 tyrosine phosphorylation within 12-24 h
      postinfection. This defect was dependent on HCMV transcription. Consequences were
      impaired nuclear translocation of STAT1-P-Tyr, inhibition of IFN-gamma activation
      site-STAT1 interaction, and inhibition of HLA-DR expression. Expression of
      indoleamine-2,3-dioxygenase which is involved in the antiviral effects of IFN
      gamma was also inhibited. Treatment of cells with sodium orthovanadate rescued
      STAT1 tyrosine phosphorylation, suggesting that a tyrosine phosphatase was
      involved in this inhibition. Coimmunoprecipitation of STAT1 and SHP2 was induced
      by HCMV infection, and SHP2 small interfering RNA restored the expression of
      STAT1-P-Tyr. Our data suggest that SHP2 activation induced by HCMV infection is
      responsible for the down-regulation of IFN-gamma-induced STAT1 tyrosine
      phosphorylation.

PMID- 18832711
TI  - Binding of complement inhibitor C4b-binding protein contributes to serum
      resistance of Porphyromonas gingivalis.
AB  - The periodontal pathogen Porphyromonas gingivalis is highly resistant to the
      bactericidal activity of human complement, which is present in the gingival
      crevicular fluid at 70% of serum concentration. All thirteen clinical and
      laboratory P. gingivalis strains tested were able to capture the human complement
      inhibitor C4b-binding protein (C4BP), which may contribute to their serum
      resistance. Accordingly, in serum deficient of C4BP, it was found that
      significantly more terminal complement component C9 was deposited on P.
      gingivalis. Moreover, using purified proteins and various isogenic mutants, we
      found that the cysteine protease high molecular weight arginine-gingipain A
      (HRgpA) is a crucial C4BP ligand on the bacterial surface. Binding of C4BP to P.
      gingivalis appears to be localized to two binding sites: on the complement
      control protein 1 domain and complement control protein 6 and 7 domains of the
      alpha-chains. Furthermore, the bacterial binding of C4BP was found to increase
      with time of culture and a particularly strong binding was observed for large
      aggregates of bacteria that formed during culture on solid blood agar medium.
      Taken together, gingipains appear to be a very significant virulence factor not
      only destroying complement due to proteolytic degradation as we have shown
      previously, but was also inhibiting complement activation due to their ability to
      bind the complement inhibitor C4BP.

PMID- 18832712
TI  - Interleukin-10 promotes Mycobacterium tuberculosis disease progression in CBA/J
      mice.
AB  - IL-10 is a potent immunomodulatory cytokine that affects innate and acquired
      immune responses. The immunological consequences of IL-10 production during
      pulmonary tuberculosis (TB) are currently unknown, although IL-10 has been
      implicated in reactivation TB in humans and with TB disease in mice. Using
      Mycobacterium tuberculosis-susceptible CBA/J mice, we show that blocking the
      action of IL-10 in vivo during chronic infection stabilized the pulmonary
      bacterial load and improved survival. Furthermore, this beneficial outcome was
      highly associated with the recruitment of T cells to the lungs and enhanced T
      cell IFN-gamma production. Our results indicate that IL-10 promotes TB disease
      progression. These findings have important diagnostic and/or therapeutic
      implications for the prevention of reactivation TB in humans.

PMID- 18832713
TI  - Dynamics of human respiratory virus-specific CD8+ T cell responses in blood and
      airways during episodes of common cold.
AB  - We determined the dynamics of CD8(+) T cells specific for influenza virus and
      respiratory syncytial virus in blood and tracheostoma aspirates of children
      during the course of respiratory infections. We showed that during localized
      respiratory infections the ratio of activated effector CD8(+) T cells to resting
      memory/naive CD8(+) T cells in peripheral blood increased significantly.
      Furthermore, the number of effector/memory T cells specific for respiratory
      viruses declined in blood and increased in the airways, suggesting that these T
      cells redistributed from blood to airways. T cells specific for the infecting
      virus were present in the airways for longer periods at increased levels than
      nonspecifically recruited bystander T cells. After clearance of the infection,
      the ratio of resting memory and naive CD8(+) T cells normalized in peripheral
      blood and also memory T cell numbers specific for unrelated viruses that declined
      during the infection due to bystander recruitment were restored. Taken together,
      these results showed a significant systemic T cell response during relatively
      mild secondary infections and extensive dynamics of virus-specific and
      nonspecific Ag-experienced T cells.

PMID- 18832714
TI  - Yersinia pestis evades TLR4-dependent induction of IL-12(p40)2 by dendritic cells
      and subsequent cell migration.
AB  - At the temperature of its flea vector (approximately 20-30 degrees C), the
      causative agent of plague, Yersinia pestis, expresses a profile of genes distinct
      from those expressed in a mammalian host (37 degrees C). When dendritic cells
      (DC) are exposed to Y. pestis grown at 26 degrees C (Y. pestis-26 degrees), they
      secrete copious amounts of IL-12p40 homodimer (IL-12(p40)(2)). In contrast, when
      DCs are exposed to Y. pestis grown at 37 degrees C (Y. pestis-37 degrees), they
      transcribe very little IL-12p40, which is secreted as IL-12p40 monomer (IL
      12p40). Y. pestis-26 degrees also induces migration of DCs to the homeostatic
      chemokine CCL19, whereas Y. pestis-37 degrees does not; migratory DCs are
      positive for IL-12p40 transcription and secrete mostly IL-12(p40)(2); DCs lacking
      IL-12p40 do not migrate. Expression of acyltransferase LpxL from Escherichia coli
      in Y. pestis-37 degrees results in the production of a hexa-acylated lipid A,
      also seen in Y. pestis-26 degrees, rather than tetra-acylated lipid A normally
      seen in Y. pestis-37 degrees. The LpxL-expressing Y. pestis-37 degrees promotes
      DC IL-12(p40)(2) production and induction of DC migration. In addition, absence
      of TLR4 ablates production of IL-12(p40)(2) in DC exposed to Y. pestis-26
      degrees. The data demonstrate the molecular pathway by which Y. pestis evades
      induction of early DC activation as measured by migration and IL-12(p40)(2)
      production.

PMID- 18832715
TI  - Evasion of complement-mediated lysis and complement C3 deposition are regulated
      by Francisella tularensis lipopolysaccharide O antigen.
AB  - The bacterium Francisella tularensis (Ft) is a potential weapon of bioterrorism
      when aerosolized. Macrophage infection is necessary for disease progression and
      efficient phagocytosis by human macrophages requires serum opsonization by
      complement. Microbial complement activation leads to surface deposition of a
      highly regulated protein complex resulting in opsonization or membrane lysis. The
      nature of complement component C3 deposition, i.e., C3b (opsonization and lysis)
      or C3bi (opsonization only) fragment deposition, is central to the outcome of
      activation. In this study, we examine the mechanisms of Ft resistance to
      complement-mediated lysis, C3 component deposition on the Ft surface, and
      complement activation. Upon incubation in fresh nonimmune human serum, Schu S4
      (Ft subsp. tularensis), Fn (Ft subsp. novicida), and LVS (Ft subsp. holarctica
      live vaccine strain) were resistant to complement-mediated lysis, but LVSG and
      LVSR (LVS strains altered in surface carbohydrate structures) were susceptible.
      C3 deposition, however, occurred on all strains. Complement-susceptible strains
      had markedly increased C3 fragment deposition, including the persistent presence
      of C3b compared with C3bi, which indicates that C3b inactivation results in
      survival of complement-resistant strains. C1q, an essential component of the
      classical activation pathway, was necessary for lysis of complement-susceptible
      strains and optimal C3 deposition on all strains. Finally, use of Francisella LPS
      mutants confirmed O Ag as a major regulator of complement resistance. These data
      provide evidence that pathogenic Francisella activate complement, but are
      resistant to complement-mediated lysis in part due to limited C3 deposition,
      rapid conversion of surface-bound C3b to C3bi, and the presence of LPS O Ag.

PMID- 18832716
TI  - CCR2 mediates homeostatic and inflammatory release of Gr1(high) monocytes from
      the bone marrow, but is dispensable for bladder infiltration in bacterial urinary
      tract infection.
AB  - CCR2 is thought to recruit monocytes to sites of infection. Two subpopulations of
      murine blood monocytes differing in Gr1 and CCR2 expression have been described.
      The exact role of CCR2 in migration of CCR2(low)Gr1(low) and CCR2(high)Gr1(high)
      monocytes into nonlymphoid tissue is controversial. In this study, we have
      addressed this question in a murine model of bacterial urinary tract infection.
      Only Gr1(high) monocytes were recruited into the infected bladder. CCR2
      deficiency reduced their frequency in this organ, indicating a requirement of
      this chemokine receptor. Importantly, CCR2-deficient mice also showed reduced
      Gr1(high) monocyte numbers in the blood, but not in the bone marrow (BM),
      indicating that CCR2 acted at the step of monocyte release into the circulation.
      The same was found also in noninfected mice, indicating a further involvement of
      CCR2 in steady-state BM egress. An additional requirement of CCR2 in monocyte
      recruitment from the blood into the bladder was excluded by tracking particle
      labeled endogenous monocytes and by adoptive transfer of BM-derived monocyte
      subsets. These findings demonstrate that CCR2 governs homeostatic and infection
      triggered release of Gr1(high) monocytes from the BM into the blood but is
      dispensable for recruitment into a nonlymphoid tissue.

PMID- 18832717
TI  - Adenylate cyclase toxin subverts phagocyte function by RhoA inhibition and
      unproductive ruffling.
AB  - Adenylate cyclase toxin (CyaA or ACT) is a key virulence factor of pathogenic
      Bordetellae. It penetrates phagocytes expressing the alpha(M)beta(2) integrin
      (CD11b/CD18, Mac-1 or CR3) and paralyzes their bactericidal capacities by
      uncontrolled conversion of ATP into a key signaling molecule, cAMP. Using pull
      down activity assays and transfections with mutant Rho family GTPases, we show
      that cAMP signaling of CyaA causes transient and selective inactivation of RhoA
      in mouse macrophages in the absence of detectable activation of Rac1, Rac2, or
      RhoG. This CyaA/cAMP-induced drop of RhoA activity yielded dephosphorylation of
      the actin filament severing protein cofilin and massive actin cytoskeleton
      rearrangements, which were paralleled by rapidly manifested macrophage ruffling
      and a rapid and unexpected loss of macropinocytic fluid phase uptake. As shown in
      this study for the first time, CyaA/cAMP signaling further caused a rapid and
      near-complete block of complement-mediated phagocytosis. Induction of
      unproductive membrane ruffling, hence, represents a novel sophisticated mechanism
      of down-modulation of bactericidal activities of macrophages and a new paradigm
      for action of bacterial toxins that hijack host cell signaling by manipulating
      cellular cAMP levels.

PMID- 18832718
TI  - Mast cell IL-6 improves survival from Klebsiella pneumonia and sepsis by
      enhancing neutrophil killing.
AB  - The pleiotropic cytokine IL-6 has favorable and harmful effects on survival from
      bacterial infections. Although many innate immune cells produce IL-6, little is
      known about relevant sources in vivo and the nature of its contributions to host
      responses to severe bacterial infections. To examine these roles, we subjected
      mast cell-specific IL-6-deficient mice to the cecal ligation and puncture model
      of septic peritonitis, finding that survival in these mice is markedly worse than
      in controls. Following intranasal or i.p. inoculation with Klebsiella pneumoniae,
      IL-6 (-/-) mice are less likely to survive than wild-type controls and at the
      time of death have higher numbers of bacteria but not inflammatory cells in lungs
      and peritoneum. Similarly, mast cell-specific IL-6-deficient mice have diminished
      survival and higher numbers of K. pneumoniae following i.p. infection.
      Neutrophils lacking IL-6 have greater numbers of live intracellular K. pneumonia,
      suggesting impaired intracellular killing contributes to reduced clearance in IL
      6(-/-) mice. These results establish that mast cell IL-6 is a critical mediator
      of survival following K. pneumoniae infection and sepsis and suggest that IL-6
      protects from death by augmenting neutrophil killing of bacteria.

PMID- 18832719
TI  - A phosphatidylserine species inhibits a range of TLR- but not IL-1beta-induced
      inflammatory responses by disruption of membrane microdomains.
AB  - TLRs detect conserved molecular patterns that are unique to microbes, enabling
      tailored responses to invading pathogens and modulating a multitude of
      immunopathological conditions. We investigated the ability of a naturally
      occurring stearoyl-arachidonoyl form of phosphatidylserine (SAPS) to inhibit the
      proinflammatory effects of TLR agonists in models of inflammation investigating
      the interaction of leukocytes with epithelial and endothelial cells. The
      responses to LPS of both epithelial and endothelial cells were highly amplified
      in the presence of PBMCs. Coincubation with SAPS markedly inhibited activation of
      cocultures by LPS, principally through inhibition of the TLR4 signaling pathway
      in PBMCs; however, this was not through downmodulation of TLR4 or coreceptor
      expression, nor was IL-1beta-induced cytokine release affected. SAPS also
      impaired Pam(3)CSK(4) (TLR2/1), Gardiquimod (TLR7/8), and Streptococcus
      pneumoniae-induced cytokine release, but had only modest effects on poly(I:C)
      (TLR3)-induced responses. Fluorescence resonance energy transfer analysis of
      molecular associations revealed that SAPS disrupted the association of both TLR4
      and TLR2 with their respective membrane partners that are required for signaling.
      Thus, our data reinforce the existence and importance of cooperative networks of
      TLRs, tissue cells, and leukocytes in mediating innate immunity, and identify a
      novel disrupter of membrane microdomains, revealing the dependence of TLR
      signaling on localization within these domains.

PMID- 18832720
TI  - Airway delivery of soluble mycobacterial antigens restores protective mucosal
      immunity by single intramuscular plasmid DNA tuberculosis vaccination: role of
      proinflammatory signals in the lung.
AB  - Protection by parenteral immunization with plasmid DNA vaccines against pulmonary
      tuberculosis (TB) is very modest. In this study, we have investigated the
      underlying mechanisms for the poor mucosal protective efficacy and the avenues
      and mechanisms to improve the efficacy of a single i.m. immunization with a
      monogenic plasmid DNA TB vaccine in a murine model. We show that i.m. DNA
      immunization fails to elicit accumulation of Ag-specific T cells in the airway
      lumen despite robust T cell responses in the spleen. Such systemically activated
      T cells cannot be rapidly mobilized into the airway lumen upon Mycobacterium
      tuberculosis exposure. However, airway deposition of low doses of soluble
      mycobacterial Ags in previously immunized mice effectively mobilizes the
      systemically activated T cells into the airway lumen. A fraction of such airway
      luminal T cells can persist in the airway lumen, undergo quick, robust expansion
      and activation and provide marked immune protection upon airway M. tuberculosis
      exposure. Airway mucosal deposition of soluble mycobacterial Ags was found to
      create a tissue microenvironment rich in proinflammatory molecules including
      chemokines and hence conducive to T cell recruitment. Thus, in vivo
      neutralization of MIP-1alpha or IFN-inducible protein-10 markedly inhibited the
      accumulation of Ag-specific T cells in the airway lumen. Our data suggest that
      immunoprotective efficacy on the mucosal surface by i.m. plasmid DNA immunization
      could be substantially improved by simple mucosal soluble Ag inoculation and
      restoration of mucosal luminal T cells. Our study holds implication for the
      future design of DNA vaccination strategies against intracellular infections.

PMID- 18832721
TI  - S-nitrosylated S100A8: novel anti-inflammatory properties.
AB  - S100A8 and S100A9, highly expressed by neutrophils, activated macrophages, and
      microvascular endothelial cells, are secreted during inflammatory processes. Our
      earlier studies showed S100A8 to be an avid scavenger of oxidants, and, together
      with its dependence on IL-10 for expression in macrophages, we postulated that
      this protein has a protective role. S-nitrosylation is an important
      posttranslational modification that regulates NO transport, cell signaling, and
      homeostasis. Relatively few proteins are targets of S-nitrosylation. To date, no
      inflammation-associated proteins with NO-shuttling capacity have been identified.
      We used HPLC and mass spectrometry to show that S100A8 and S100A9 were readily S
      nitrosylated by NO donors. S-nitrosylated S100A8 (S100A8-SNO) was the preferred
      nitrosylated product. No S-nitrosylation occurred when the single Cys residue in
      S100A8 was mutated to Ala. S100A8-SNO in human neutrophils treated with NO donors
      was confirmed by the biotin switch assay. The stable adduct transnitrosylated
      hemoglobin, indicating a role in NO transport. S100A8-SNO suppressed mast cell
      activation by compound 48/80; intravital microscopy was used to demonstrate
      suppression of leukocyte adhesion and extravasation triggered by compound 48/80
      in the rat mesenteric microcirculation. Although S100A8 is induced in macrophages
      by LPS or IFN-gamma, the combination, which activates inducible NO synthase, did
      not induce S100A8. Thus, the antimicrobial functions of NO generated under these
      circumstances would not be compromised by S100A8. Our results suggest that S100A8
      SNO may regulate leukocyte-endothelial cell interactions in the microcirculation,
      and suppression of mast cell-mediated inflammation represents an additional anti
      inflammatory property for S100A8.

PMID- 18832722
TI  - Prostaglandin E2 signals monocyte/macrophage survival to peroxynitrite via
      protein kinase A converging in bad phosphorylation with the protein kinase C
      alpha-dependent pathway driven by 5-hydroxyeicosatetraenoic acid.
AB  - Monocytes/macrophages committed to death by peroxynitrite nevertheless survive
      with a signaling response promoting Bad phosphorylation, as well as its cytosolic
      localization, via upstream activation of cytosolic phospholipase A(2), 5
      lipoxygenase, and protein kinase C alpha. We now report evidence for an
      alternative mechanism converging in Bad phosphorylation when the
      expression/activity of the above enzymes are suppressed. Under these conditions,
      also associated with peroxynitrite-dependent severe inhibition of Akt, an
      additional Bad kinase, Bad dephosphorylation promoted its accumulation in the
      mitochondria and a prompt lethal response. PGE(2) prevented toxicity via EP(2)
      receptor-mediated protein kinase A-dependent Bad phosphorylation. This notion was
      established in U937 cells by the following criteria: 1) there was a strong
      correlation between survival and cAMP accumulation, both in the absence and
      presence of phosphodiesterase inhibitors; 2) direct activation of adenylyl
      cyclase afforded cytoprotection; and 3) PGE(2) promoted loss of mitochondrial Bad
      and cytoprotection, mimicked by EP(2) receptor agonists, and prevented by EP(2)
      receptor antagonists or protein kinase A inhibitors. Finally, selected
      experiments performed in human monocytes/macrophages and in rat peritoneal
      macrophages indicated that the above cytoprotective pathway is a general response
      of cells belonging to the monocyte/macrophage lineage to both exogenous and
      endogenous peroxynitrite. The notion that two different pathways mediated by
      downstream products of arachidonic acid metabolism converge in Bad
      phosphorylation emphasizes the relevance of this strategy for the regulation of
      macrophage survival to peroxynitrite at the inflammatory sites.

PMID- 18832723
TI  - Sumoylation of peroxisome proliferator-activated receptor gamma by apoptotic
      cells prevents lipopolysaccharide-induced NCoR removal from kappaB binding sites
      mediating transrepression of proinflammatory cytokines.
AB  - Efficient clearance of apoptotic cells (AC) by professional phagocytes is crucial
      for tissue homeostasis and resolution of inflammation. Macrophages respond to AC
      with an increase in antiinflammatory cytokine production but a diminished release
      of proinflammatory mediators. Mechanisms to explain attenuated proinflammatory
      cytokine formation remain elusive. We provide evidence that peroxisome
      proliferator-activated receptor gamma (PPARgamma) coordinates antiinflammatory
      responses following its activation by AC. Exposing murine RAW264.7 macrophages to
      AC before LPS stimulation reduced NF-kappaB transactivation and lowered target
      gene expression of, that is, TNF-alpha and IL-6 compared with controls. In
      macrophages overexpressing a dominant negative mutant of PPARgamma, NF-kappaB
      transactivation in response to LPS was restored, while macrophages from myeloid
      lineage-specific conditional PPARgamma knockout mice proved that PPARgamma
      transmitted an antiinflammatory response, which was delivered by AC. Expressing a
      PPARgamma-Delta aa32-250 deletion mutant, we observed no inhibition of NF-kappaB.
      Analyzing the PPARgamma domain structures within aa 32-250, we anticipated
      PPARgamma sumoylation in mediating the antiinflammatory effect in response to AC.
      Interfering with sumoylation of PPARgamma by mutating the predicted sumoylation
      site (K77R), or knockdown of the small ubiquitin-like modifier (SUMO) E3 ligase
      PIAS1 (protein inhibitor of activated STAT1), eliminated the ability of AC to
      suppress NF-kappaB. Chromatin immunoprecipitation analysis demonstrated that AC
      prevented the LPS-induced removal of nuclear receptor corepressor (NCoR) from the
      kappaB site within the TNF-alpha promoter. We conclude that AC induce PPARgamma
      sumoylation to attenuate the removal of NCoR, thereby blocking transactivation of
      NF-kappaB. This contributes to an antiinflammatory phenotype shift in macrophages
      responding to AC by lowering proinflammatory cytokine production.

PMID- 18832724
TI  - Overproduction of IgE induces macrophage-derived chemokine (CCL22) secretion from
      basophils.
AB  - Macrophage-derived chemokine (MDC) CCL22 is a potent chemoattractant for Th2
      cells and has been implicated in Th2-predominant allergic inflammation. In the
      present study, we demonstrated that basophils produce MDC in response to
      monomeric IgE. In trinitrophenyl (TNP)-IgE transgenic mice, serum levels of MDC
      were persistently higher than in wild-type mice. The i.v. administration of TNP
      specific IgE to wild-type mice transiently induced an elevation in serum MDC,
      which appeared to be mediated by Fc epsilonRI, as no increase in serum MDC was
      observed after IgE administration in FcRgamma (-/-) mice. However, the IgE
      mediated increase in MDC was observed in mast cell-deficient mice. Freshly
      isolated bone marrow cells and bone marrow-derived basophils secreted MDC in
      response to TNP-IgE without Ag stimulation. Furthermore, MDC production was not
      observed in bone marrow-derived basophils isolated from FcRgamma (-/-) mice. IgE
      activated Lyn and ERK 1/2 in bone marrow-derived basophils. Treatment of TNP-IgE
      transgenic mice with a basophil-depletion Ab (Ba103) resulted in decreased serum
      MDC levels. Thus, IgE appears to be capable of stimulating basophils to produce
      MDC in the absence of a specific Ag, which may contribute to IgE-mediated and/or
      Th2-predominant allergic inflammation.

PMID- 18832725
TI  - The vitamin D3/Hox-A10 pathway supports MafB function during the monocyte
      differentiation of human CD34+ hemopoietic progenitors.
AB  - Although a considerable number of reports indicate an involvement of the Hox-A10
      gene in the molecular control of hemopoiesis, the conclusions of such studies are
      quite controversial given that they support, in some cases, a role in the
      stimulation of stem cell self-renewal and myeloid progenitor expansion, whereas
      in others they implicate this transcription factor in the induction of monocyte
      macrophage differentiation. To clarify this issue, we analyzed the biological
      effects and the transcriptome changes determined in human primary CD34(+)
      hemopoietic progenitors by retroviral transduction of a full-length Hox-A10 cDNA.
      The results obtained clearly indicated that this homeogene is an inducer of
      monocyte differentiation, at least partly acting through the up-regulation of the
      MafB gene, recently identified as the master regulator of such a maturation
      pathway. By using a combined approach based on computational analysis, EMSA
      experiments, and luciferase assays, we were able to demonstrate the presence of a
      Hox-A10-binding site in the promoter region of the MafB gene, which suggested the
      likely molecular mechanism underlying the observed effect. Stimulation of the
      same cells with the vitamin D(3) monocyte differentiation inducer resulted in a
      clear increase of Hox-A10 and MafB transcripts, indicating the existence of a
      precise transactivation cascade involving vitamin D(3) receptor, Hox-A10, and
      MafB transcription factors. Altogether, these data allow one to conclude that the
      vitamin D(3)/Hox-A10 pathway supports MafB function during the induction of
      monocyte differentiation.

PMID- 18832726
TI  - Macrophage migration inhibitory factor plays a role in the regulation of
      microfold (M) cell-mediated transport in the gut.
AB  - It has been shown previously that certain bacteria rapidly (3 h) up-regulated in
      vivo microfold cell (M cell)-mediated transport of Ag across the follicle
      associated epithelium of intestinal Peyer's patch. Our aim was to determine
      whether soluble mediators secreted following host-bacteria interaction were
      involved in this event. A combination of proteomics and immunohistochemical
      analyses was used to identify molecules produced in the gut in response to
      bacterial challenge in vivo; their effects were then tested on human intestinal
      epithelial cells in vitro. Macrophage migration inhibitory factor (MIF) was the
      only cytokine produced rapidly after in vivo bacterial challenge by CD11c(+)
      cells located beneath the M cell-rich area of the follicle-associated epithelium
      of the Peyer's patch. Subsequently, in vitro experiments conducted using human
      Caco-2 cells showed that, within hours, MIF induced the appearance of cells that
      showed temperature-dependent transport of microparticles and M cell-specific
      bacterium Vibrio cholerae, and acquired biochemical features of M cells.
      Furthermore, using an established in vitro human M cell model, we showed that
      anti-MIF Ab blocked Raji B cell-mediated conversion of Caco-2 cells into Ag
      sampling cells. Finally, we report that MIF(-/-) mice, in contrast to wild-type
      mice, failed to show increased M cell-mediated transport following in vivo
      bacterial challenge. These data show that MIF plays a role in M cell-mediated
      transport, and cross-talk between bacteria, gut epithelium, and immune system is
      instrumental in regulating key functions of the gut, including M cell-mediated Ag
      sampling.

PMID- 18832727
TI  - Stat4 isoforms differentially regulate inflammation and demyelination in
      experimental allergic encephalomyelitis.
AB  - Experimental allergic encephalomyelitis (EAE) is a T cell-mediated autoimmune
      disease model of multiple sclerosis. Signal transducer and activator of
      transcription 4 (Stat4) is a transcription factor activated by IL-12 and IL-23,
      two cytokines known to play important roles in the pathogenesis of EAE by
      inducing T cells to secrete IFN-gamma and IL-17, respectively. We and others have
      previously shown that therapeutic intervention or targeted disruption of Stat4
      was effective in ameliorating EAE. Recently, a splice variant of Stat4 termed
      Stat4beta has been characterized that lacks 44 amino acids at the C terminus of
      the full-length Stat4alpha. In this study we examined whether T cells expressing
      either isoform could affect the pathogenesis of EAE. We found that transgenic
      mice expressing Stat4beta on a Stat4-deficient background develop an exacerbated
      EAE compared with wild-type mice following immunization with myelin
      oligodendrocyte glycoprotein peptide 35-55, while Stat4alpha transgenic mice have
      greatly attenuated disease. The differential development of EAE in transgenic
      mice correlates with increased IFN-gamma and IL-17 in Stat4beta-expressing cells
      in situ, contrasting increased IL-10 production by Stat4alpha-expressing cells.
      This study demonstrates that Stat4 isoforms differentially regulate inflammatory
      cytokines in association with distinct effects on the onset and severity of EAE.

PMID- 18832728
TI  - Differential effects of GM-CSF and G-CSF on infiltration of dendritic cells
      during early left ventricular remodeling after myocardial infarction.
AB  - Several lines of evidence suggest that the immune activation after myocardial
      infarction (MI) induces secondary myocardial injury. Although dendritic cells
      (DC) are potent regulators of immunity, their role in MI is still undetermined.
      We investigated the effect of DC modulation by CSF on left ventricular (LV)
      remodeling after MI. MI was induced by ligation of the left coronary artery in
      male Wistar rats. G-CSF (20 microg/kg/day, MI-G, n = 33), a GM-CSF inducer
      (romurtide, 200 microg/kg/day, MI-GM, n = 28), or saline (MI-C, n = 55) was
      administered for 7 days. On day 14, MI-G animals had higher LV max dP/dt and
      smaller LV dimensions, whereas MI-GM animals had lower LV max dP/dt and larger LV
      dimensions than did MI-C animals, despite similar infarct size. In MI-C, OX62(+)
      DC infiltrated the infarcted and border areas, peaking on day 7.
      Bromodeoxyuridine-positive DC were observed in the border area during
      convalescence. Infiltration by DC was decreased in MI-G animals and increased in
      MI-GM animals compared with MI-C (p < 0.05). In the infarcted area, the heat
      shock protein 70, TLR2 and TLR4, and IFN-gamma expression were reduced in MI-G,
      but increased in MI-GM in comparison with those in MI-C animals. IL-10 expression
      was higher in MI-G and lower in MI-GM than in MI-C animals. In conclusion, G-CSF
      improves and GM-CSF exacerbates early postinfarction LV remodeling in association
      with modulation of DC infiltration. Suppression of DC-mediated immunity could be
      a new strategy for the treatment of LV remodeling after MI.

PMID- 18832729
TI  - Neutrophil-mediated activation of epithelial protease-activated receptors-1 and 
      2 regulates barrier function and transepithelial migration.
AB  - Neutrophil (PMN) infiltration and associated release of serine proteases
      contribute to epithelial injury during active phases of mucosal disorders such as
      inflammatory bowel disease. Previous studies have demonstrated that PMN contact
      with basolateral surfaces of intestinal epithelial cells in the presence of a
      chemoattractant results in disruption of barrier function even without
      transmigration. Similarly, serine protease-mediated activation of epithelial
      protease-activated receptors (PARs) has been shown to increase permeability. In
      this study, we assessed whether transmigrating PMNs can regulate barrier function
      through epithelial PAR activation. Transepithelial resistance (TER) decreased
      significantly after PMN contact with basolateral surfaces of T84 monolayers or
      after incubation with PMN elastase and proteinase-3, but not cathepsin G.
      Inhibition of PMN serine proteases, but not selective inhibition of elastase or
      cathepsin G, prevented the fall in TER induced by PMN contact and blocked PMN
      transepithelial migration. Basolateral, but not apical, PAR-1 and -2 activation
      with selective agonists also decreased TER. PAR-1 and -2 were localized
      intracellularly and in close proximity to lateral surfaces beneath tight
      junctions, and expression was increased in colonic mucosa from individuals with
      Crohn's disease. Combined, but not individual, transfection with small
      interfering RNAs targeted against epithelial PAR-1 and -2, prevented the fall in
      TER induced by PMN contact. Furthermore, basolateral PAR-1 and -2 activation
      induced phosphorylation of myosin L chain kinase and regulatory myosin L chain.
      Lastly, epithelial PAR-1 and -2 knockdown decreased the rate of PMN
      transepithelial migration. These results suggest that protease-mediated
      epithelial PAR-1 and -2 activation, by migrating PMNs, induces signaling events
      that increase epithelial permeability thereby facilitates PMN transepithelial
      migration.

PMID- 18832730
TI  - The angiogenic response of the aorta to injury and inflammatory cytokines
      requires macrophages.
AB  - The purpose of this study was to define early events during the angiogenic
      response of the aortic wall to injury. Rat aortic rings produced neovessels in
      collagen culture but lost this capacity over time. These quiescent rings
      responded to vascular endothelial growth factor but not to a mixture of
      macrophage-stimulatory cytokines and chemokines that was angiogenically active on
      fresh rings. Analysis of cytokine receptor expression revealed selective loss in
      quiescent rings of the proangiogenic chemokine receptor CXCR2, which was
      expressed predominantly in aortic macrophages. Pharmacologic inhibition of CXCR2
      impaired angiogenesis from fresh rings but had no effect on vascular endothelial
      growth factor-induced angiogenesis from quiescent explants. Angiogenesis was also
      impaired in cultures of aortic rings from CXCR2-deficient mice. Reduced CXCR2
      expression in quiescent rat aortic rings correlated with marked macrophage
      depletion. Pharmacologic ablation of macrophages from aortic explants blocked
      formation of neovessels in vitro and reduced aortic ring-induced angiogenesis in
      vivo. The angiogenic response of macrophage-depleted rings was completely
      restored by adding exogenous macrophages. Moreover, angiogenesis from fresh rings
      was promoted by macrophage CSF (CSF-1) and inhibited with anti-CSF-1 Ab. Thus,
      aortic angiogenic sprouting following injury is strongly influenced by conditions
      that modulate resident macrophage numbers and function.

PMID- 18832731
TI  - IL-23 inhibits osteoclastogenesis indirectly through lymphocytes and is required
      for the maintenance of bone mass in mice.
AB  - IL-23 stimulates the differentiation and function of the Th17 subset of CD4(+) T
      cells and plays a critical role in chronic inflammation. The IL-23 receptor
      encoding gene is also an inflammatory disease susceptibility gene. IL-23 shares a
      common subunit with IL-12, a T cell-dependent osteoclast formation inhibitor, and
      we found that IL-23 also dose-dependently inhibited osteoclastogenesis in a
      CD4(+) T lymphocyte-dependent manner. When sufficiently enriched, gammadelta T
      cells also mediated IL-23 inhibition. Like IL-12, IL-23 acted synergistically
      with IL-18 to block osteoclastogenesis but, unlike IL-12, IL-23 action depended
      on T cell GM-CSF production. IL-23 did not mediate IL-12 action although IL-12
      induced its expression. Male mice lacking IL-23 (IL-23p19(-/-)) had approximately
      30% lower bone mineral density and tibial trabecular bone mass (bone volume
      (BV)/total volume (TV)) than wild-type littermates at 12 wk and 40% lower BV/TV
      at 26 wk of age; male heterozygotes also had lower bone mass. Female IL-23p19(-/
      ) mice also had reduced BV/TV. IL-23p19(-/-) mice had no detectable osteoclast
      defect in trabecular bone but IL-23p19(-/-) had thinner growth plate hypertrophic
      and primary spongiosa zones (and, in females, less cartilage remnants) compared
      with wild type. This suggests increased osteoclast action at and below the growth
      plate, leading to reduced amounts of mature trabecular bone. Thus, IL-23 inhibits
      osteoclast formation indirectly via T cells in vitro. Under nonpathological
      conditions (unlike inflammatory conditions), IL-23 favors higher bone mass in
      long bones by limiting resorption of immature bone forming below the growth
      plate.

PMID- 18832732
TI  - Functional consequences of neuromyelitis optica-IgG astrocyte interactions on
      blood-brain barrier permeability and granulocyte recruitment.
AB  - Autoantibody neuromyelitis optica-IgG (NMO-IgG) recognizing aquaporin-4 (AQP4) is
      implicated as playing a central role in the physiopathology of NMO. The aim of
      this in vitro-based study was to characterize functional consequences of
      interaction between NMO-IgG and cells of the neurovascular unit (astrocytes and
      brain endothelium) that would provide insight into recognized features of NMO,
      namely altered blood-brain barrier (BBB) permeability and granulocyte
      recruitment. We used sera from NMO and longitudinally extensive transverse
      myelitis cases shown to bind in a characteristic perivascular pattern to primate
      cerebellar slices. Using flow cytometry, we found that sera from NMO-IgG-positive
      patients reacted with CNS-derived human fetal astrocytes, whereas sera from
      multiple sclerosis patients did not. We demonstrated that NMO-IgG binding to
      astrocytes alters aquaporin-4 polarized expression and increases permeability of
      a human BBB endothelium/astrocyte barrier. We further demonstrated that NMO-IgG
      binding to human fetal astrocytes can result in NK cell degranulation, astrocyte
      killing by Ab-dependent cellular cytotoxicity and complement-dependent
      granulocyte attraction through the BBB model. Our study highlights important
      functional roles for NMO-IgG that could account for pathological lesions and BBB
      dysfunction observed in NMO.

PMID- 18832733
TI  - Anti-type V collagen humoral immunity in lung transplant primary graft
      dysfunction.
AB  - Primary graft dysfunction (PGD) is a major complication following lung
      transplantation. We reported that anti-type V collagen (col(V)) T cell immunity
      was strongly associated with PGD. However, the role of preformed anti-col(V) Abs
      and their potential target in PGD are unknown. Col(V) immune serum, purified IgG
      or B cells from col(V) immune rats were transferred to WKY rat lung isograft
      recipients followed by assessments of lung pathology, cytokines, and
      PaO(2)/FiO(2), an index of lung dysfunction in PGD. Immune serum, purified IgG,
      and B cells all induced pathology consistent with PGD within 4 days posttransfer;
      up-regulated IFN-gamma, TNF-alpha, and IL-1beta locally; and induced significant
      reductions in PaO(2)/FiO(2). Depleting anti-col(V) Abs before transfer
      demonstrated that IgG2c was a major subtype mediating injury. Confocal microscopy
      revealed strong apical col(V) expression on lung epithelial, but not endothelial
      cells; which was consistent with the ability of col(V) immune serum to induce
      complement-dependent cytotoxicity only in the epithelial cells. Examination of
      plasma from patients with or without PGD revealed that higher levels of preformed
      anti-col(V) Abs were strongly associated with PGD development. This study
      demonstrates a major role for anti-col(V) humoral immunity in PGD, and identifies
      the airway epithelium as a target in PGD.

PMID- 18832734
TI  - Tolerance without clonal expansion: self-antigen-expressing B cells program self
      reactive T cells for future deletion.
AB  - B cells have been shown in various animal models to induce immunological
      tolerance leading to reduced immune responses and protection from autoimmunity.
      We show that interaction of B cells with naive T cells results in T cell
      triggering accompanied by the expression of negative costimulatory molecules such
      as PD-1, CTLA-4, B and T lymphocyte attenuator, and CD5. Following interaction
      with B cells, T cells were not induced to proliferate, in a process that was
      dependent on their expression of PD-1 and CTLA-4, but not CD5. In contrast, the T
      cells became sensitive to Ag-induced cell death. Our results demonstrate that B
      cells participate in the homeostasis of the immune system by ablation of
      conventional self-reactive T cells.

PMID- 18832735
TI  - Decreased expression of intelectin 1 in the human airway epithelium of smokers
      compared to nonsmokers.
AB  - Lectins are innate immune defense proteins that recognize bacterial cell wall
      components. Based on the knowledge that cigarette smoking is associated with an
      increased risk of infections, we hypothesized that cigarette smoking may modulate
      the expression of lectin genes in airway epithelium. Affymetrix microarrays were
      used to survey the expression of lectin genes in large airway epithelium from
      nine nonsmokers and 20 healthy smokers and in small airway epithelium from 13
      nonsmokers and 20 healthy smokers. There were no changes (>2-fold change; p <
      0.05) in lectin gene expression among healthy smokers compared with nonsmokers
      except for down-regulation of intelectin 1, a lectin that binds to
      galactofuranosyl residues in bacterial cell walls (large airway epithelium, p <
      0.01; small airway epithelium, p < 0.01). This was confirmed by TaqMan RT-PCR in
      both large (p < 0.05) and small airway epithelium (p < 0.02).
      Immunohistochemistry assessment of airway biopsies demonstrated that intelectin 1
      was expressed in secretory cells, while Western analysis confirmed the decreased
      expression of intelectin 1 in airway epithelium of healthy smokers compared with
      healthy nonsmokers (p < 0.02). Finally, compared with healthy nonsmokers,
      intelectin 1 expression was also decreased in small airway epithelium of smokers
      with lone emphysema and normal spirometry (n = 13, p < 0.01) and smokers with
      established chronic obstructive pulmonary disease (n = 14, p < 0.01). In the
      context that intelectin 1 plays a role in defense against bacteria, its down
      regulation in response to cigarette smoking is another example of the
      immunomodulatory effects of smoking on the immune system and may contribute to
      the increase in susceptibility to infections observed in smokers.

PMID- 18832736
TI  - B cells from patients with Graves' disease aberrantly express the IGF-1 receptor:
      implications for disease pathogenesis.
AB  - Graves' disease (GD) is an autoimmune process involving the thyroid and
      connective tissues in the orbit and pretibial skin. Activating anti-thyrotropin
      receptor Abs are responsible for hyperthyroidism in GD. However, neither these
      autoAbs nor the receptor they are directed against have been convincingly
      implicated in the connective tissue manifestations. Insulin-like growth factor-1
      receptor (IGF-1R)-bearing fibroblasts overpopulate connective tissues in GD and
      when ligated with IgGs from these patients, express the T cell chemoattractants,
      IL-16, and RANTES. Disproportionately large fractions of peripheral blood T cells
      also express IGF-1R in patients with GD and may account, at least in part, for
      expansion of IGF-1R(+) memory T cells. We now report a similarly skewed B cell
      population exhibiting the IGF-1R(+) phenotype from the blood, orbit, and bone
      marrow of patients with GD. This expression profile exhibits durability in
      culture and is maintained or increased with CpG activation. Moreover, IGF-1R(+) B
      cells produce pathogenic Abs against the thyrotropin receptor. In lymphocytes
      from patients with GD, IGF-1 enhanced IgG production (p < 0.05) and increased B
      cell expansion (p < 0.02) in vitro while those from control donors failed to
      respond. These findings suggest a potentially important role for IGF-1R display
      by B lymphocytes in patients with GD in supporting their expansion and abnormal
      Ig production.

PMID- 18832737
TI  - Periodontitis associates with a type 1 IFN signature in peripheral blood
      neutrophils.
AB  - Peripheral blood neutrophils from periodontitis patients exhibit a hyperreactive
      and hyperactive phenotype (collectively termed hyperresponsivity) in terms of
      production of reactive oxygen species (ROS). The molecular basis for this
      phenomenon, however, has yet to be determined. Our objectives were to identify
      genes differentially expressed in hyperresponsive peripheral blood neutrophils
      from chronic periodontitis patients relative to periodontally healthy controls
      and use these data to identify potential contributory pathways to the
      hyperresponsive neutrophil phenotype. Using microarray technology we demonstrated
      differential expression of 163 genes (149 increased, 14 decreased) representing a
      range of ontological classes. There was increased expression of a significant
      number of IFN-stimulated genes (ISG). RT-PCR analysis of ISG transcripts in
      individual and pooled samples further corroborated these data, and indicated that
      levels decreased to near those of controls following successful therapy.
      Significantly enhanced FcgammaR-stimulated ROS production was subsequently
      achieved by priming control neutrophils with IFN-alpha/-beta/-gamma, but not LPS,
      and gene expression analysis indicated that exposure to the type I IFN (in
      particular IFN-alpha) better replicated the mRNA profile observed in vivo.
      Further studies demonstrated that plasma levels of IFN-alpha were significantly
      higher in samples from patients relative to unaffected controls. Following
      successful periodontitis treatment, plasma IFN-alpha levels, neutrophil ISG
      expression, and FcgammaR-stimulated neutrophil ROS output of patients, all
      decreased to levels comparable with those of controls. In conclusion, although
      chronic periodontitis is a complex disease, raised IFN-alpha may be one
      determinant of the distinct molecular phenotype and hyperresponsivity exhibited
      by patients' peripheral blood neutrophils.

PMID- 18832738
TI  - Effect of CpG oligonucleotides on vaccine-induced B cell memory.
AB  - Adding synthetic oligodeoxynucleotides containing unmethylated CpG motifs to
      Anthrax vaccine adsorbed (AVA, the licensed human vaccine) increases the speed
      and magnitude of the resultant Ab response. Ab titers persist in the protective
      range for >1 year, significantly longer than in animals vaccinated with AVA
      alone. Unexpectedly, a majority of mice immunized with CpG-adjuvanted AVA
      maintained resistance to anthrax infection even after their Ab titers had
      declined into the subprotective range. The survival of these animals was mediated
      by the de novo production of protective Abs by high affinity memory B cells re
      stimulated immediately after challenge. Thus, a previously unrecognized benefit
      of CpG oligodeoxynucleotides adjuvants is their ability to expand the long-lived
      memory B cell population. Current findings demonstrate that CpG-adjuvanted AVA
      mediates protection both by stimulating a strong/persistent serum Ab response and
      by generating a high-affinity long-lived pool of memory B cells.

PMID- 18832740
TI  - Rabbit subselective angiography stroke model.

PMID- 18832739
TI  - Subsets of myeloid-derived suppressor cells in tumor-bearing mice.
AB  - Myeloid-derived suppressor cells (MDSC) are a heterogeneous group of cells that
      play a critical role in tumor associated immune suppression. In an attempt to
      identify a specific subset of MDSC primarily responsible for immunosuppressive
      features of these cells, 10 different tumor models were investigated. All models
      showed variable but significant increase in the population of MDSC. Variability
      of MDSC expansion in vivo matched closely the effect of tumor cell condition
      medium in vitro. MDSC consists of two major subsets of Ly6G(+)Ly6C(low)
      granulocytic and Ly6G(-)Ly6C(high) monocytic cells. Granulocytic MDSC have
      increased level of reactive oxygen species and undetectable level of NO whereas
      monocytic MDSC had increased level of NO but undetectable levels of reactive
      oxygen species. However, their suppressive activity per cell basis was
      comparable. Almost all tumor models demonstrated a preferential expansion of
      granulocytic subset of MDSC. We performed a phenotypical and functional analysis
      of several surface molecules previously suggested to be involved in MDSC-mediated
      suppression of T cells: CD115, CD124, CD80, PD-L1, and PD-L2. Although
      substantial proportion of MDSC expressed those molecules no differences in the
      level of their expression or the proportion, positive cells were found between
      MDSC and cells from tumor-free mice that lack immune suppressive activity. The
      level of MDSC-mediated T cell suppression did not depend on the expression of
      these molecules. These data indicate that suppressive features of MDSC is caused
      not by expansion of a specific subset but more likely represent a functional
      state of these cells.

PMID- 18832741
TI  - Increased stroke risk is related to a binge-drinking habit.
AB  - BACKGROUND AND PURPOSE: Heavy alcohol consumption increases the risk for all
      strokes, whereas moderate regular alcohol consumption is associated with a lower
      risk for ischemic stroke. The purpose of this study was to evaluate the effect of
      different drinking patterns on stroke risk, independent of average alcohol
      intake. METHODS: A prospective cohort study of 15 965 Finnish men and women age
      25 to 64 years who participated in a national risk factor survey and had no
      history of stroke at baseline were followed up for a 10-year period. The first
      stroke event during follow-up served as the outcome of interest (N=249 strokes).
      A binge drinking pattern was defined as consuming 6 or more drinks of the same
      alcoholic beverage in men or 4 or more drinks in women in 1 session. Cox
      proportional-hazards models were adjusted for average alcohol consumption, age,
      sex, hypertension, smoking, diabetes, body mass index, educational status, study
      area, study year, and history of myocardial infarction. RESULTS: Binge drinking
      was an independent risk factor for total and ischemic strokes. Compared with non
      binge drinkers, the hazard ratio for total strokes among binge drinkers was 1.85
      (95% CI, 1.35 to 2.54) after adjusting for average alcohol consumption, age, and
      sex; the association was diluted after adjustment for other risk factors.
      Compared with non-binge drinkers, the risk for ischemic stroke was 1.99 (95% CI,
      1.39 to 2.87) among binge drinkers; the association remained statistically
      significant after adjustment for potential confounders. CONCLUSIONS: This study
      found that a pattern of binge drinking is an independent risk factor for all
      strokes and ischemic stroke.

PMID- 18832742
TI  - Detection of right-to-left shunt with transcranial Doppler is affected by body
      positioning.

PMID- 18832743
TI  - Hemorrhagic stroke in the SPARCL study.

PMID- 18832744
TI  - Effect of prazosin on dynamic cerebral autoregulation during acute hypotension in
      healthy human subjects.

PMID- 18832745
TI  - Racial differences in vascular risk factors and outcomes of patients with
      intracranial atherosclerotic arterial stenosis.
AB  - BACKGROUND AND PURPOSE: Atherosclerotic intracranial stenosis is an important
      cause of stroke in blacks, yet there are limited data on vascular risk factors
      and outcome. We analyzed the vascular risk factors and outcomes of blacks and
      whites in the Warfarin versus Aspirin for Symptomatic Intracranial Disease
      (WASID) trial. METHODS: Baseline characteristics and outcomes (ischemic stroke,
      brain hemorrhage, or vascular death combined and ischemic stroke alone) were
      compared between blacks (n=174) and whites (n=331) using univariate and
      multivariate analyses. RESULTS: Blacks were significantly (P<0.05) more likely
      than whites to be/have: female, hypertension history, diabetes history, higher
      LDL, higher total cholesterol, lower triglycerides, unmarried, unemployed,
      nonprivate insurance, no insurance, stroke as qualifying event, <70% stenosis,
      symptomatic anterior circulation vessel, no antithrombotic medication before
      qualifying event, and no family history of myocardial infarction. Blacks more
      frequently reached an end point of ischemic stroke, brain hemorrhage or vascular
      death (28% versus 20%; hazard ratio of 1.49, 95% CI 1.03 to 2.17, P=0.03), had a
      higher 2-year event rate (0.28 versus 0.19), and reached the end point of
      ischemic stroke alone (25% versus 16% at 2 years; hazard ratio of 1.62, P=0.017).
      In multivariate analysis, race was associated with ischemic stroke (P=0.0488) but
      not with the end point ischemic stroke, brain hemorrhage or vascular death
      (P=0.188). CONCLUSIONS: Blacks with intracranial stenosis are at higher risk of
      stroke recurrence than whites. This risk warrants additional study of factors
      contributing to stroke in blacks and highlights the need for aggressive risk
      factor management in blacks to prevent recurrence.

PMID- 18832746
TI  - Dyslipidemia and atherosclerosis induced by chronic intermittent hypoxia are
      attenuated by deficiency of stearoyl coenzyme A desaturase.
AB  - Obstructive sleep apnea leads to chronic intermittent hypoxia (CIH) and is
      associated with atherosclerosis. We have previously shown that C57BL/6J mice
      exposed to CIH and a high-cholesterol diet develop dyslipidemia, atherosclerosis
      of the aorta, and upregulation of a hepatic enzyme of lipoprotein secretion,
      stearoyl coenzyme A desaturase 1 (SCD-1). We hypothesized that (1) SCD-1
      deficiency will prevent dyslipidemia and atherosclerosis during CIH; and (2)
      human OSA is associated with dyslipidemia and upregulation of hepatic SCD.
      C57BL/6J mice were exposed to CIH or normoxia for 10 weeks while being treated
      with either SCD-1 or control antisense oligonucleotides. Obese human subjects
      underwent sleep study and bariatric surgery with intraoperative liver biopsy. In
      mice, hypoxia increased hepatic SCD-1 and plasma very-low-density lipoprotein
      cholesterol levels and induced atherosclerosis lesions in the ascending aorta
      (the cross-section area of 156514+/-57408 microm(2)), and descending aorta (7.0+/
      1.2% of the total aortic surface). In mice exposed to CIH and treated with SCD-1
      antisense oligonucleotides, dyslipidemia and atherosclerosis in the ascending
      aorta were abolished, whereas lesions in the descending aorta showed 56%
      reduction. None of the mice exposed to normoxia developed atherosclerosis. In
      human subjects, hepatic SCD mRNA levels correlated with the degree of nocturnal
      hypoxemia (r=0.68, P=0.001). Patients exhibiting oxyhemoglobin desaturations at
      night showed higher plasma triglyceride and low-density lipoprotein cholesterol
      levels, compared to subjects without hypoxemia. In conclusion, CIH is associated
      with dyslipidemia and overexpression of hepatic SCD in both humans and mice
      alike; SCD-1 deficiency attenuates CIH-induced dyslipidemia and atherosclerosis
      in mice.

PMID- 18832747
TI  - Adenosine 5'-tetraphosphate is a highly potent purinergic endothelium-derived
      vasoconstrictor.
AB  - Besides serving as a mechanical barrier, the endothelium has important regulatory
      functions. The discovery of nitric oxide revolutionized our understanding of
      vasoregulation. In contrast, the identity of endothelium-derived vasoconstrictive
      factors still remains uncertain. The supernatant from mechanically stimulated
      human microvascular endothelial cells elicited a potent vasoconstrictive response
      in the isolated perfused rat kidney. Whereas a nonselective purinoceptor blocker
      blocked this vasoactivity most potently, the inhibition of the endothelin
      receptor by BQ123 weakly affected that vasoconstrictive response. As a compound
      responsible for that vasoconstrictive effect, we have isolated from HMECs and
      identified the mononucleotide adenosine 5'-tetraphosphate (AP4). This nucleotide
      proved to be the most potent vasoactive purinergic mediator identified to date,
      exerting the vasoconstriction predominantly through activation of the P2X1
      receptor. The intraarterial application of AP4 in a Wistar-Kyoto rat induced a
      strong increase of the mean arterial pressure. The plasma concentration of AP4 is
      in the nanomolar range, which, in vivo, induces a significant change in the mean
      arterial pressure. To our knowledge, AP4, which exerts vasoactive effects, is the
      most potent endogenous mononucleotide identified to date in mammals. The effects
      of AP4, the plasma concentration of AP4, and its release suggest that this
      compound functions as an important vasoregulator.

PMID- 18832748
TI  - CD11c(+) dendritic cells maintain antigen processing, presentation capabilities,
      and CD4(+) T-cell priming efficacy under hypercholesterolemic conditions
      associated with atherosclerosis.
AB  - Recent reports suggest dyslipidemia impairs dendritic cell (DC) function and
      adaptive immunity. This study aimed to characterize the effect of
      hypercholesterolemia on antigen-presenting cell function of DCs and DC-dependent
      CD4(+) T-cell responses. DCs incubated in vitro with acetylated low-density
      lipoprotein cholesterol with or without an acyl-coenzyme A:cholesterol acyl
      transferase inhibitor maintained their ability to prime CD4(+) T cells. Analysis
      of T-cell proliferation and interferon-gamma and tumor necrosis factor-alpha
      production after ex vivo coculture of naive CD4(+) T cells with splenic,
      inguinal, or iliac DCs from low-density lipoprotein receptor-deficient (LDLR(-/
      )) or apolipoprotein E-deficient (ApoE(-/-)) mice fed an atherogenic diet
      highlighted DC efficacy in effector T-cell generation under hypercholesterolemic
      conditions. Adoptive transfer of carboxyfluorescein diacetate, succinimidyl ester
      (CFSE)-labeled naive CD4(+) T cells in LDLR(-/-) recipients and subsequent
      immunization demonstrated effective priming of naive T cells in
      hypercholesterolemic mice. CFSE dilution analyses revealed that
      hypercholesterolemic DCs were equipotent in naive CD4(+) T-cell priming efficacy
      with normocholesterolemic DCs. Quantitative real-time PCR and flow cytometric
      analyses demonstrated that DC expression of multiple molecules involved in
      antigen processing, presentation, and T-cell stimulation remained unaltered by
      dyslipidemia. Finally, endogenous antigen-primed CD4(+) T cells responded
      equivalently to a secondary ex vivo antigenic challenge, regardless of whether
      they were primed in vivo under hypercholesterolemic or control conditions,
      demonstrating that all essential steps in CD4(+) T-cell responses remain intact
      under atherogenic conditions. This study affirms that the adaptive immune
      response prevails under the hypercholesterolemic conditions present in
      atherosclerosis. In particular, DCs remain functional antigen-presenting cells
      and maintain their ability to prime CD4(+) T cells even when cholesterol-loaded.

PMID- 18832749
TI  - Ca2+ influx through T- and L-type Ca2+ channels have different effects on myocyte
      contractility and induce unique cardiac phenotypes.
AB  - T-type Ca(2+) channels (TTCCs) are expressed in the developing heart, are not
      present in the adult ventricle, and are reexpressed in cardiac diseases involving
      cardiac dysfunction and premature, arrhythmogenic death. The goal of this study
      was to determine the functional role of increased Ca(2+) influx through
      reexpressed TTCCs in the adult heart. A mouse line with cardiac-specific,
      conditional expression of the alpha1G-TTCC was used to increase Ca(2+) influx
      through TTCCs. alpha1G hearts had mild increases in contractility but no cardiac
      histopathology or premature death. This contrasts with the pathological phenotype
      of a previously studied mouse with increased Ca(2+) influx through the L-type
      Ca(2+) channel (LTCC) secondary to overexpression of its beta2a subunit. Although
      alpha1G and beta2a myocytes had similar increases in Ca(2+) influx, alpha1G
      myocytes had smaller increases in contraction magnitude, and, unlike beta2a
      myocytes, there were no increases in sarcoplasmic reticulum Ca(2+) loading.
      Ca(2+) influx through TTCCs also did not induce normal sarcoplasmic reticulum
      Ca(2+) release. alpha1G myocytes had changes in LTCC, SERCA2a, and phospholamban
      abundance, which appear to be adaptations that help maintain Ca(2+) homeostasis.
      Immunostaining suggested that the majority of alpha1G-TTCCs were on the surface
      membrane. Osmotic shock, which selectively eliminates T-tubules, induced a
      greater reduction in L- versus TTCC currents. These studies suggest that T- and
      LTCCs are in different portions of the sarcolemma (surface membrane versus T
      tubules) and that Ca(2+) influx through these channels induce different effects
      on myocyte contractility and lead to distinct cardiac phenotypes.

PMID- 18832750
TI  - Vascular endothelial growth factor-A and platelet-derived growth factor-B
      combination gene therapy prolongs angiogenic effects via recruitment of
      interstitial mononuclear cells and paracrine effects rather than improved
      pericyte coverage of angiogenic vessels.
AB  - Vessel stabilization and the inhibition of side effects such as tissue edema are
      essential in angiogenic gene therapy. Thus, combination gene transfers
      stimulating both endothelial cell and pericyte proliferation have become of
      interest. However, there is currently little data to support combination gene
      transfer in large animal models. In this study, we evaluated the potential
      advantages of such a strategy by combining the transfer of adenoviral (Ad)
      vascular endothelial growth factor (VEGF)-A and platelet-derived growth factor
      (PDGF)-B into rabbit hindlimb skeletal muscle. AdLacZ alone or in combination
      with AdVEGF-A were used as controls. Contrast-enhanced ultrasound, modified Miles
      assay, and immunohistology were used to quantify perfusion, vascular
      permeability, and capillary size, respectively. Confocal microscopy was used in
      the assessment of pericyte-coverage. The transfer of AdPDGF-B alone and in
      combination with AdVEGF-A induced prominent proliferation of alpha-smooth muscle
      actin-, CD31-, RAM11-, HAM56-, and VEGF- positive cells. Although, pericyte
      recruitment to angiogenic vessels was not improved, combination gene transfer
      induced a longer-lasting increase in perfusion in both intact and ischemic
      muscles than AdVEGF-A gene transfer alone. In conclusion, intramuscular delivery
      of AdVEGF-A and AdPDGF-B, combined, resulted in a prolonged angiogenic response.
      However, the effects were most likely mediated via paracrine mechanisms rather
      than an increase in vascular pericyte coverage.

PMID- 18832751
TI  - Infusion of reconstituted high-density lipoprotein leads to acute changes in
      human atherosclerotic plaque.
AB  - Studies have shown a reduction in plaque volume and change in plaque ultrasound
      characteristics after 4 infusions of reconstituted high-density lipoprotein
      (rHDL). Whether rHDL infusion leads to acute changes in plaque characteristics in
      humans is not known. Patients with claudication scheduled for percutaneous
      superficial femoral artery revascularization were randomized to receive 1
      intravenous infusion of either placebo or rHDL (80 mg/kg given over 4 hours).
      Five to 7 days following the infusion, patients returned and revascularization
      was performed including atherectomy to excise plaque from the superficial femoral
      artery. Twenty patients (17 males) average age, 68+/-10 years (mean+/-SD) were
      recruited. Eleven patients had a history of documented coronary artery disease,
      all patients were on aspirin, and 18 were on statins. Ten of the patients
      received rHDL and 10 placebo. There was significantly less vascular cell adhesion
      molecule-1 expression (28+/-3% versus 50+/-3%; P<0.05) and a reduction in lipid
      content in the plaque of HDL-treated subjects compared to placebo. The level of
      HDL cholesterol increased by 20% after infusion of rHDL and the capacity of
      apolipoprotein B-depleted plasma to support cholesterol efflux increased.
      Intravenous infusion of a single dose of reconstituted HDL led to acute changes
      in plaque characteristics with a reduction in lipid content, macrophage size, and
      measures of inflammation. These changes may contribute to the cardioprotective
      effects of HDL.

PMID- 18832752
TI  - Genome-wide analysis of the zebrafish ETS family identifies three genes required
      for hemangioblast differentiation or angiogenesis.
AB  - ETS domain transcription factors have been linked to hematopoiesis,
      vasculogenesis, and angiogenesis. However, their biological functions and the
      mechanisms of action, remain incompletely understood. Here, we have performed a
      systematic analysis of zebrafish ETS domain genes and identified 31 in the
      genome. Detailed gene expression profiling revealed that 12 of them are expressed
      in blood and endothelial precursors during embryonic development. Combined with a
      phylogenetic tree assay, this suggests that some of the coexpressed genes may
      have redundant or additive functions in these cells. Loss-of-function analysis of
      3 of them, erg, fli1, and etsrp, demonstrated that erg and fli1 act cooperatively
      and are required for angiogenesis possibly via direct regulation of an
      endothelial cell junction molecule, VE-cadherin, whereas etsrp is essential for
      primitive myeloid/endothelial progenitors (hemangioblasts) in zebrafish. Taken
      together, these results provide a global view of the ETS genes in the zebrafish
      genome during embryogenesis and provide new insights on the functions and biology
      of erg, fli1, and etsrp, which could be applicable to higher vertebrates,
      including mice and humans.

PMID- 18832753
TI  - Hypercholesterolemia enhances 15-lipoxygenase-mediated vasorelaxation and
      acetylcholine-induced hypotension.
AB  - OBJECTIVE: Arachidonic acid (AA) metabolites from 15-lipoxygenase-1 (15-LO-1),
      trihydroxyeicosatrienoic acid (THETA), and hydroxyepoxyeicosatrienoic acid
      (HEETA) relax arteries. We studied 15-LO-1 expression, THETA and HEETA synthesis,
      and their effect on arterial relaxations and blood pressure in
      hypercholesterolemic nonatherosclerotic rabbits. METHODS AND RESULTS:
      Immunoblots, RTPCR analysis, and (14)C-AA metabolism revealed that
      hypercholesterolemia increased 15-LO-1 expression in the endothelium and THETA
      and HEETA synthesis in the arteries. Isometric tension recording, in presence of
      nitric oxide synthase (NOS) and cyclooxygenase (COX) inhibitors, showed greater
      relaxations to acetylcholine (ACH) and AA (max 76.0+/-4.6% and 79.5+/-2.4%,
      respectively) in aortas from hypercholesterolemic rabbits compared with normal
      rabbits (max 39.1+/-2.8% and 39.9+/-2.2%, respectively). AA induced greater
      hyperpolarization in the smooth muscle cells of hypercholesterolemic aortas (
      45.85+/-3.0 mV) compared with normal aortas (-31.45+/-1.9 mV). The ACH- and AA
      relaxations were inhibited by 15-LO-1 inhibitors. ACH induced hypotensive
      responses were greater in hypercholesterolemic rabbits in absence (-54.9+/-3.3%)
      or presence (-48.5+/-3.2%) of NOS and COX-inhibitors compared with control
      rabbits (-31.6+/-3.3% and -24.3+/-1.6%, respectively). BW755C reduced these
      responses in hypercholesterolemic rabbits to -29.3+/-2.3%. CONCLUSIONS:
      Hypercholesterolemia increases endothelial 15-LO-1 expression, THETA and HEETA
      synthesis and enhances vasorelaxation.

PMID- 18832754
TI  - Clones of interstitial cells from bovine aortic valve exhibit different
      calcifying potential when exposed to endotoxin and phosphate.
AB  - OBJECTIVE: Our purpose was to study in vitro whether phenotypically-distinct
      interstitial cell clones from bovine aortic valve (BVIC) possess different
      calcifying potential in response to endotoxin (lipopolysaccharide [LPS]) and
      phosphate (Pi). METHODS AND RESULTS: Among various clones of BVIC obtained by
      limited dilution technique we selected 4 clones displaying different growth
      patterns and immunophenotypes. Uncloned and cloned cells were treated with
      combinations of LPS (100 ng/mL) and Pi (2.4 mmol/L). Uncloned BVIC showed
      increased alkaline phosphatase activity (ALP) after treatment with LPS, which
      resulted in calcification after addition of Pi. Among BVIC clones, only Clone 1
      (fibroblast-like phenotype) showed a relevant increase in ALP after LPS treatment
      in parallel with prevention of smooth muscle (SM) alpha-actin accumulation. No
      effect was observed in clonal cells harboring a more stable SM cell-like profile
      (Clone 4). None of the isolated clones calcified but mineralization was induced
      in the presence of LPS plus Pi when Clone 1 was cocultured with Clone 4 or after
      seeding on type I collagen sponges. CONCLUSIONS: Endotoxin and phosphate can act
      as valve calcification promoters by targeting specific fibroblast-like
      interstitial valve cells that possess a unique procalcific potential.

PMID- 18832755
TI  - Mitochondrial apoptotic signaling is elevated in cardiac but not skeletal muscle
      in the obese Zucker rat and is reduced with aerobic exercise.
AB  - Mitochondrial apoptosis and apoptotic signaling modulations by aerobic training
      were studied in cardiac and skeletal muscles of obese Zucker rats (OZR), a rodent
      model of metabolic syndrome. Comparisons were made between left ventricle,
      soleus, and gastrocnemius muscles from OZR (n = 16) and aged-matched lean Zucker
      rats (LZR; n = 16) that were untrained (n = 8) or aerobically trained on a
      treadmill for 9 wk (n = 8). Cardiac Bcl-2 protein expression levels were
      approximately 50% lower in the OZR compared with the LZR, with no difference in
      either of the skeletal muscles. Bax protein expression levels were similar in
      skeletal muscles of the OZR compared with the LZR. Furthermore, mitochondrial
      apoptotic signaling was not different in skeletal muscles of OZR and LZR groups.
      However, there was an approximate sevenfold increase in the Bax protein
      accumulation in the myocardial mitochondrial-rich protein fraction of the OZR
      compared with the LZR. Additionally, there was an increase in cytosolic
      cytochrome c released from the mitochondria, caspase-9 and caspase-3 activity,
      with a corresponding elevation in DNA fragmentation in the cardiac muscles of the
      OZR compared with the LZR. Exercise training reduced cardiac Bax protein levels,
      the mitochondrial localization of Bax, cytosolic cytochrome c, caspase activity,
      and DNA fragmentation in cardiac muscles of the OZR after exercise, with no
      change in the skeletal muscles. These data show that mitochondrial apoptosis is
      elevated in the cardiac but not skeletal muscles of the OZR, but aerobic exercise
      training was effective in reducing cardiac mitochondrial apoptotic signaling.

PMID- 18832756
TI  - Effect of resistance exercise on muscle steroidogenesis.
AB  - Circulating testosterone is elevated acutely following resistance exercise (RE)
      and is an important anabolic hormone for muscle adaptations to resistance
      training. The purpose of this study was to examine the acute effect of heavy RE
      on intracrine muscle testosterone production in young resistance-trained men and
      women. Fifteen young, highly resistance-trained men (n = 8; 21 +/- 1 yr, 175.3 +/
      6.7 cm, 90.8 +/- 11.6 kg) and women (n = 7; 24 +/- 5 yr, 164.6 +/- 6.7 cm, 76.4
      +/- 15.6 kg) completed 6 sets of 10 repetitions of Smith machine squats with 80%
      of their 1-repetition maximum. Before RE and 10 and 70 min after RE, muscle
      biopsies were obtained from the vastus lateralis. Before RE, after 3 and 6 sets
      of squats, and 5, 15, 30, and 70 min into recovery from RE, blood samples were
      obtained using venipuncture from an antecubital vein. Muscle samples were
      analyzed for testosterone, 17beta-hydroxysteroid dehydrogenase (HSD) type 3, and
      3beta-HSD type 1 and 2 content. Blood samples were analyzed for glucose and
      lactate concentrations. No changes were found for muscle testosterone, 3beta-HSD
      type 1 and 2, and 17beta-HSD type 3 concentrations. However, a change in protein
      migration in the Bis-Tris gel was observed for 17beta-HSD type 3 postexercise;
      this change in migration indicated an approximately 2.8 kDa increase in molecular
      mass. These findings indicate that species differences in muscle testosterone
      production may exist between rats and humans. In humans, muscle testosterone
      concentrations do not appear to be affected by RE. This study expands on the
      current knowledge obtained from animal studies by examining resting and
      postexercise concentrations of muscle testosterone and steroidogenic enzymes in
      humans.

PMID- 18832757
TI  - Effects of exercise training and hypercholesterolemia on adenosine activation of
      voltage-dependent K+ channels in coronary arterioles.
AB  - Coronary arterioles from hypercholesterolemic swine display attenuated adenosine
      mediated vasodilatation that is attributable to the elimination of voltage
      dependent K(+) (Kv) channel stimulation. For the present study, we tested the
      hypotheses that exercise training would correct impaired adenosine-induced
      dilatation in coronary arterioles from hypercholesterolemic pigs through
      restoration of adenosine activation of Kv channels and that vasodilatation to the
      receptor-independent adenylyl cyclase activator, forskolin, would also be
      attenuated in arterioles from hypercholesterolemic pigs. Pigs were randomly
      assigned to a control (NC) or high-fat, high-cholesterol (HC) diet for 20 wk.
      Four weeks after the diet was initiated, pigs from both groups were assigned to
      exercise training (Ex; 5 days/wk for 16 wk) or sedentary (Sed) protocols,
      resulting in four groups of pigs: NC-Sed, NC-Ex, HC-Sed, and HC-Ex. Arterioles (
      approximately 150 mum) from both HC-Sed and HC-Ex pigs displayed impaired
      adenosine-mediated dilatation that was attributable to the elimination of 4
      aminopyridine (4-AP; 1 mM)-sensitive Kv channel activation compared with NC
      counterparts. Arteriolar smooth muscle whole cell Kv currents were significantly
      reduced in HC-Sed compared with NC-Sed, although HC-Ex and NC-Ex did not differ.
      Forskolin-mediated dilatation was attenuated by 4-AP (1 mM) and in a
      concentration-dependent manner by tetraethylammonium (TEA; 0.1-1 mM) in NC-Sed
      but not HC-Sed. Further, TEA-sensitive Kv currents were diminished in cells of HC
      Sed compared with NC-Sed pigs. Quantitative RT-PCR revealed similar expression
      levels of Kv3.1 and 3.3 in arterioles of NC-Sed and HC-Sed swine with
      undetectable expression of Kv1.1, 3.2, and 3.4. Taken together, these results
      suggest that hypercholesterolemia-mediated attenuation of adenosine-induced
      vasodilatation in coronary arterioles is not corrected by exercise training and
      is likely attributable to an impairment in the pathway coupling adenylyl cyclase
      with a highly TEA-sensitive Kv channel isoform(s).

PMID- 18832758
TI  - Partitioning of nasal and pulmonary resistance changes during noninvasive
      plethysmography in mice.
AB  - Double-chamber plethysmography is a well established noninvasive method of
      assessing airflow obstruction in small lab animals. It allows measurement of the
      specific airway resistance (sRaw), which unlike enhanced pause (Penh), is a
      meaningful airway mechanics parameter. Since sRaw is measured in spontaneously
      breathing mice, a limitation of the method is the inability to exclude nasal
      resistance changes. We recently showed that mice are not truly obligate nasal
      breathers and that after nasal occlusion, nasally breathing mice can transition
      to an oral mode of breathing. We now show that it is experimentally possible to
      algebraically separate the average nasal and pulmonary (including laryngeal)
      components of total airway resistance change by a series of measurements made
      across groups of mice breathing nasally or orally, assuming that oral resistance
      remains constant. Using this approach, we show that nasal resistance change
      comprises one-half or more of the total resistance change during methacholine
      challenge. Inhibition of mucin secretion from airway goblet cells attenuates
      pulmonary but not nasal airway hyperresponsiveness (AHR), and nasal AHR in a
      murine model of rhinitis may be related to edema.

PMID- 18832759
TI  - Regulation of caspase-3 activity by insulin in skeletal muscle cells involves
      both PI3-kinase and MEK-1/2.
AB  - A hallmark of skeletal muscle atrophy is increased activities of several
      proteolytic systems, including caspase-3. We have previously shown that
      conditions involving insulin deficiency or insulin resistance increase both
      overall protein degradation and caspase-3-mediated actin cleavage. In the present
      experiments, we examined how insulin regulates caspase-3 activity in L6 myotubes.
      Reducing the serum concentration in the culture media from 2 to 0.5% overnight
      increased caspase-3 activity and actin cleavage. Addition of insulin to
      proteolytically active cells attenuated both responses within 4 h. Individually,
      inhibitors of either phosphatidylinositide 3-kinase (PI3K) or MEK1/2 partially
      blocked the insulin-induced reduction in caspase-3 activity; in combination, the
      inhibitors completely prevented insulin from attenuating caspase-3 activity.
      Insulin suppressed caspase-3 activity by a complex mechanism that included direct
      inhibition due to an increased interaction between caspase-3 and cellular
      inhibitor of apoptosis-1 and indirect inhibition via phosphorylation (i.e.,
      inactivation) of the proapoptotic protein Bad, which participates in the
      intrinsic (i.e., mitochondrial) apoptosis activation cascade. Unlike other cell
      types, the phosphorylation of Bad Ser112 was mediated by the PI3K/Akt pathway
      rather than the MEK/ERK/ribosomal S6 protein kinase pathway. In summary, our
      findings indicate that insulin regulates caspase-3 activity by a multistep
      process that is unique to skeletal muscle, thus providing insights about the
      muscle-specific nature of the atrophy process.

PMID- 18832760
TI  - (Over)training effects on quantitative electromyography and muscle enzyme
      activities in standardbred horses.
AB  - Too intensive training may lead to overreaching or overtraining. To study whether
      quantitative needle electromyography (QEMG) is more sensitive to detect training
      (mal)adaptation than muscle enzyme activities, 12 standardbred geldings trained
      for 32 wk in age-, breed-, and sex-matched fixed pairs. After a habituation and
      normal training (NT) phase (phases 1 and 2, 4 and 18 wk, respectively), with
      increasing intensity and duration and frequency of training sessions, an
      intensified training (IT) group (phase 3, 6 wk) and a control group (which
      continued training as in the last week of phase 2) were formed. Thereafter, all
      horses entered a reduced training phase (phase 4, 4 wk). One hour before a
      standardized exercise test (SET; treadmill), QEMG analysis and biochemical enzyme
      activity were performed in muscle or in biopsies from vastus lateralis and
      pectoralis descendens muscle in order to identify causes of changes in exercise
      performance and eventual (mal)adaptation in skeletal muscle. NT resulted in a
      significant adaptation of QEMG parameters, whereas in muscle biopsies hexokinase
      activity was significantly decreased. Compared with NT controls, IT induced a
      stronger adaptation (e.g., higher amplitude, shorter duration, and fewer turns)
      in QEMG variables resembling potentially synchronization of individual motor unit
      fiber action potentials. Despite a 19% decrease in performance of the SET after
      IT, enzyme activities of 3-hydroxyacyl dehydrogenase and citrate synthase
      displayed similar increases in control and IT animals. We conclude that 1) QEMG
      analysis is a more sensitive tool to monitor training adaptation than muscle
      enzyme activities but does not discriminate between overreaching and normal
      training adaptations at this training level and 2) the decreased performance as
      noted in this study after IT originates most likely from a central (brain) rather
      than peripheral level.

PMID- 18832761
TI  - Physical activity: does long-term, high-intensity exercise in horses result in
      tendon degeneration?
AB  - This study explores the hypothesis that high-intensity exercise induces
      degenerative changes in the injury-prone equine superficial digital flexor tendon
      (SDFT), but not in the rarely injured common digital extensor tendon (CDET). The
      horse represents a large-animal model that is applicable to human tendon and
      ligament physiology and pathology. Twelve age-matched female horses undertook
      galloping exercise three times a week with trotting exercise on alternative days
      (high-intensity group, n = 6) or only walking exercise (low-intensity group, n =
      6) for 18 mo. The SDFT, suspensory ligament, deep digital flexor tendon, and CDET
      were harvested from the forelimb. Tissue from the mid-metacarpal region of the
      right limb tendons was analyzed for water, DNA, sulfated glycosaminoglycan and
      collagen content, collagen type III-to-I ratios, collagen cross-links, and tissue
      fluorescence. Left limb tendons were mechanically tested to failure. The analyses
      showed matrix composition to have considerable diversity between the functionally
      different structures. In addition, the specific structures responded differently
      to the imposed exercise. High-intensity training resulted in a significant
      decrease in the GAG content in the SDFT, but no change in collagen content,
      despite a decrease in collagen fibril diameters. There were no signs of
      degeneration or change in mechanical properties of the SDFT. The CDET had a lower
      water content following high-intensity training and a higher elastic modulus.
      Long-term, high-intensity training in skeletally mature individuals results in
      changes that suggest accelerated aging in the injury-prone SDFT and adaptation in
      the CDET.

PMID- 18832762
TI  - Differences in ischemia-reperfusion-induced endothelial changes in hearts
      perfused at constant flow and constant pressure.
AB  - Isolated hearts subjected to ischemia-reperfusion (I/R) exhibit depressed cardiac
      performance and alterations in subcellular function. Since hearts perfused at
      constant flow (CF) and constant pressure (CP) show differences in their
      contractile response to I/R, this study was undertaken to examine mechanisms
      responsible for these I/R-induced alterations in CF-perfused and CP-perfused
      hearts. Rat hearts, perfused at CF (10 ml/min) or CP (80 mmHg), were subjected to
      I/R (30 min global ischemia followed by 60 min reperfusion), and changes in
      cardiac function as well as sarcolemmal (SL) Na(+)-K(+)-ATPase activity,
      sarcoplasmic reticulum (SR) Ca(2+) uptake, and endothelial function were
      monitored. The I/R-induced depressions in cardiac function, SL Na(+)-K(+)-ATPase,
      and SR Ca(2+)-uptake activities were greater in hearts perfused at CF than in
      hearts perfused at CP. In hearts perfused at CF, I/R-induced increase in calpain
      activity and decrease in nitric oxide (NO) synthase (endothelial NO synthase)
      protein content in the heart as well as decrease in NO concentration of the
      perfusate were greater than in hearts perfused at CP. These changes in
      contractile activity and biochemical parameters due to I/R in hearts perfused at
      CF were attenuated by treatment with l-arginine, a substrate for NO synthase,
      while those in hearts perfused at CP were augmented by treatment with N(G)-nitro
      l-arginine methyl ester, an inhibitor of NO synthase. The results indicate that
      the I/R-induced differences in contractile responses and alterations in
      subcellular organelles between hearts perfused at CF and CP may partly be
      attributed to greater endothelial dysfunction in CF-perfused hearts than that in
      CP-perfused hearts.

PMID- 18832763
TI  - Violence against women: unveiling the suffering of women with a low income in
      Jordan.
AB  - The descriptive qualitative study documents experiences of Jordanian women abused
      by their husbands. Thirteen married women living with an abusive husband were
      recruited from a major primary healthcare center. The women described forms,
      intensity, and consequences of their husband's acts. Despite their anguish, women
      justified, normalized, and tolerated abuse; this acceptance reflected their
      cultural values and norms. Implications for nursing practice include (a)
      identifying abused women, (b) empowering them with knowledge to change their
      sociocultural perceptions of marital relationships, (c) designing interventions
      that address their needs, and (d) educating health care providers to take a role
      in addressing spousal abuse.

PMID- 18832764
TI  - Deceptive simplicity.

PMID- 18832765
TI  - Long-term effects of political violence: narrative inquiry across a 20-year
      period.
AB  - The study of long-term effects of political violence generally concentrates on
      effects of a single event or period of violence on individuals or groups of
      individuals and commonly relies on recollections from those who experienced
      violence a long time after the event. Against the backdrop of Northern Ireland's
      Troubles, in this article we use narrative inquiry methodology to explore the
      long-term effects of violence across a 20-year period on a different level. Using
      two sets of interview data, one collected 20 years ago during a period of intense
      violence and the other collected recently, after the ceasefires when levels of
      community violence had decreased, we allow for comparisons of contemporaneous
      experiences and personal narratives that illustrate differences and similarities
      across a 20-year period. Personal accounts of violent experiences, individual
      coping and psychological health, social support needs and provision, and
      political and cultural change mirrored fluctuating levels of community violence
      across time, showed growing levels of societal awareness of victims' issues and
      increasing levels of service provision, and illustrated the effects of
      postceasefire violence.

PMID- 18832766
TI  - Team meetings in specialist palliative care: asking questions as a strategy
      within interprofessional interaction.
AB  - In this article, I explore what happens when specialist palliative care staff
      meet together to discuss patients under their care. Many studies (e.g., Atkinson)
      have discussed how health care practitioners in various settings use rhetorical
      strategies when presenting cases in situations such as ward rounds and team
      meetings. Strategies for arguing and persuading are central to medical practice
      in the interprofessional context. The context of specialist palliative care is an
      interesting place for research, as there is a history of patient-centered
      holistic approaches to care, within a multidisciplinary context, that is
      interdisciplinary in its focus, structure, and practice (e.g., Saunders). This
      article examines the rhetorical accomplishment of teamwork in specialist
      palliative care settings.

PMID- 18832767
TI  - Knowledge legitimacy: how trans-patient behavior supports and challenges current
      medical knowledge.
AB  - In this article, I examine the accounts of transsexual/transgender patients and
      their involvement with medical professionals in the Midwestern United States.
      Data are taken from 22 in-depth interviews and one year of participant
      observation of three transsexual/transgender organizations. I show that trans
      patients are made aware of larger political, religious, and cultural ideologies
      through their medical experiences. Trans-patients internalize these views, which
      affect how they make sense of their medical treatment and how they choose to
      alter their behavior in future medical encounters. Trans-patients, in an attempt
      to gain credibility and avoid stigmas, prepare how they will approach doctors to
      improve their likelihood of receiving desired treatments. The data will reveal
      that through their approach, trans-patients both support and challenge existing
      medical knowledge. Patients support medical discourse by using established
      medical language in their interaction with doctors. Patients challenge medical
      knowledge by resisting established medical decisions.

PMID- 18832768
TI  - "I am not a robot!" Interpreters' views of their roles in health care settings.
AB  - In this study, I examined interpreters' self-perceived roles and their
      corresponding communicative goals and strategies. Twenty-six professional
      interpreters (of 17 languages), 4 patients, and 12 health care providers were
      recruited for this study, which involved participant observation of medical
      encounters and in-depth interviews. Constant comparative analysis was used to
      generate a typology of interpreters' self-perceived roles, which are different
      from the roles they learned in their training. Different roles reflect
      differences in interpreters' concern for other participants' goals, institutional
      goals, and their own communicative goals. Interpreters' desire to maintain
      neutrality during the medical encounters influences the communicative strategies
      they adopt when assuming other roles. I conclude the article with the theoretical
      and practical implications of interpreters' self-perceived roles.

PMID- 18832769
TI  - Breaking the silence surrounding hepatitis C by promoting self-efficacy:
      hepatitis C public service announcements.
AB  - Hepatitis C virus (HCV) is the most common chronic bloodborne virus in the United
      States. Despite this fact, there is a startling lack of awareness about HCV among
      individuals who might have contracted the virus. In this study, grounded in self
      efficacy theory, we analyze public service announcements for HCV. Using focus
      groups to contextualize the responses of individuals living with HCV, we conclude
      that stigma and structural barriers pose the greatest challenges for health
      communicators trying to reach at-risk populations. The findings suggest that
      expanded use of celebrity appeals, realistic drug-use portrayals, more extensive
      use of social networking in tandem with nontraditional media, tapping into
      veterans, and maximizing self-efficacy messages while minimizing fear tactics
      offer new hope for successful health communication strategies. With 3.9 million
      people in the United States infected with HCV, this study offers urgently needed
      communication strategies to address this silent epidemic.

PMID- 18832771
TI  - Using a voice-centered relational method of data analysis in a feminist study
      exploring the working world of nursing unit managers.
AB  - In this article, we discuss the application of a data analysis method used in a
      feminist study that explored the working world of nursing unit managers in
      Australia. The decision to use a voice-centered relational approach to the data
      was based on a desire to delve into the working world of nursing unit managers
      and uncover the layers within the narratives that specifically related to their
      perceptions of themselves, their world, and the context in which they work.
      Throughout this article, the focus is on how this method was applied to uncover
      multiple layers of meaning within the data, rather than on the researchers' and
      participants' roles in the coconstruction of interview data. An excerpt from an
      interview transcript is used to illustrate how the stories of the participants
      were explored using this method.

PMID- 18832772
TI  - A sensitive and specific ELISA detects methionine sulfoxide-containing
      apolipoprotein A-I in HDL.
AB  - Oxidized HDL has been proposed to play a key role in atherogenesis. A wide range
      of reactive intermediates oxidizes methionine residues to methionine sulfoxide
      (MetO) in apolipoprotein A-I (apoA-I), the major HDL protein. These reactive
      species include those produced by myeloperoxidase, an enzyme implicated in
      atherogenesis. The aim of the present study was to develop a sensitive and
      specific ELISA for detecting MetO residues in HDL. We therefore immunized mice
      with HPLC-purified human apoA-I containing MetO(86) and MetO(112) (termed apoA
      I(+32)) to generate a monoclonal antibody termed MOA-I. An ELISA using MOA-I
      detected lipid-free apoA-I(+32), apoA-I modified by 2e-oxidants (hydrogen
      peroxide, hypochlorous acid, peroxynitrite), and HDL oxidized by 1e- or 2e
      oxidants and present in buffer or human plasma. Detection was concentration
      dependent, reproducible, and exhibited a linear response over a physiologically
      plausible range of concentrations of oxidized HDL. In contrast, MOA-I failed to
      recognize native apoA-I, native apoA-II, apoA-I modified by hydroxyl radical or
      metal ions, or LDL and methionine-containing proteins other than apoA-I modified
      by 2e-oxidants. Because the ELISA we have developed specifically detects apoA-I
      containing MetO in HDL and plasma, it should provide a useful tool for
      investigating the relationship between oxidized HDL and coronary artery disease.

PMID- 18832774
TI  - N-acetylcysteine for the prevention of atrial fibrillation: beyond its
      antioxidant effect.

PMID- 18832773
TI  - Profiles of structural heterogeneity in native lipooligosaccharides of Neisseria
      and cytokine induction.
AB  - Fine differences in the phosphorylation and acylation of lipooligosaccharide
      (LOS) from Neisseria species are thought to profoundly influence the virulence of
      the organisms and the innate immune responses of the host, such as signaling
      through toll-like receptor 4 (TLR4) and triggering receptor expressed on myeloid
      cells (TREM). MALDI time-of-flight (TOF) mass spectrometry was used to
      characterize heterogeneity in the native LOS from Neisseria gonorrheae and N.
      meningitidis. A sample preparation methodology previously reported for
      Escherichia coli lipopolysaccharide (LPS) employing deposition of untreated LOS
      on a thin layer of a film composed of 2,4,6-trihydroxyacetophenone and
      nitrocellulose was used. Prominent peaks were observed corresponding to molecular
      ions and to fragment ions primarily formed by cleavage between the 3-deoxy-D
      manno-oct-2-ulosonic acid (Kdo) and the lipid A (LA). Analyses of these data and
      comparison with spectra of the corresponding O-deacylated or hydrogen fluoride
      treated LOS enabled the detection of novel species that apparently differed by
      the expression of up to three phosphates with one or more phosphoethanolamine
      (PEA) groups on the LA. We found that the heterogeneity profile of acylation and
      phosphorylation correlates with the induction of proinflammatory cytokines in THP
      1 monocytic cells. This methodology enabled us to rapidly profile components of
      structural variants of native LOS that are of importance biologically.

PMID- 18832775
TI  - Atherosclerosis of the aorta in patients with acute thoracic aortic dissection.
AB  - BACKGROUND: The role of atherosclerosis in thoracic aortic dissection has not
      been established yet. Transesophageal echocardiography (TEE) is an imaging
      modality widely used in the diagnostic evaluation of thoracic aortic dissection,
      and it can detect aortic atherosclerotic plaques and assess their size and
      specific characteristics. METHODS AND RESULTS: One hundred consecutive patients
      with thoracic aortic dissection and adequate imaging of the thoracic aorta by TEE
      were studied. The type of dissection (proximal or distal) and the presence and
      the degree of aortic atherosclerosis were defined. Proximal aortic dissection
      (Stanford type A) was found in 64 patients. Patients with proximal dissection
      were younger than those with distal (type B; 58+/-13 vs 67+/-11 years, p<0.001).
      The prevalence of arterial hypertension was higher in patients with distal
      dissection compared with those with proximal. Aortic atherosclerosis was present
      in less patients with proximal than with distal dissection (67% vs 94%, p<0.002).
      Logistic regression analysis revealed that patients with severe atherosclerosis
      were 7.6-fold more probable to have type B than type A dissection (p<0.001).
      CONCLUSION: Aortic atherosclerosis is more associated with distal than with
      proximal aortic dissection.

PMID- 18832776
TI  - Clinical significance of cerebral oxygenation during exercise in patients with
      coronary artery disease.
AB  - BACKGROUND: Recent investigations have demonstrated that cerebral oxyhemoglobin
      (O(2)Hb) decreases during exercise in patients with left ventricular dysfunction,
      reflecting a cerebral hypoxia. We sought to establish a prognostic value of
      decreased cerebral O(2)Hb during exercise in cardiac patients, and to compare it
      with those of indexes obtained from cardiopulmonary exercise testing (CPX).
      METHODS AND RESULTS: A total of 344 consecutive patients with coronary artery
      disease were enrolled in the study. All the patients performed CPX, during which
      cerebral O(2)Hb was continuously monitored using near-infrared spectroscopy.
      There were 13 cardiac deaths and 78 cardiovascular events during the prospective
      follow-up period of 1,231+/-538 days. The change of O(2)Hb measured at the
      forehead from rest to peak exercise (DeltaO(2)Hb) was significantly lower in non
      survivors than in survivors (-1.5+/-3.3 vs 1.7+/-3.2 micromol/L, p=0.0004). By
      multivariate Cox proportional hazards analysis, DeltaO(2)Hb and left ventricular
      ejection fraction (LVEF) were found to be independent prognostic markers for
      cardiac deaths. The DeltaO(2)Hb, LVEF and peak oxygen uptake were found to be
      significant prognostic markers for cardiovascular events, mainly for heart
      failure worsening and sudden cardiac death. CONCLUSION: The present findings
      suggest that a decrease in cerebral O(2)Hb during exercise predicts future
      cardiovascular events in patients with coronary artery disease.

PMID- 18832777
TI  - Evaluation of the antiplatelet effects of cilostazol, a phosphodiesterase 3
      inhibitor, by VASP phosphorylation and platelet aggregation.
AB  - BACKGROUND: Cilostazol, a phosphodiesterase 3 inhibitor, is an antiplatelet drug
      that is widely used for preventing cardiovascular events, although, to date,
      there are few methods for evaluating its effects. METHODS AND RESULTS: Blood
      samples were taken at baseline and at 3 and 12 h in 10 healthy male subjects
      after 100 mg cilostazol intake. Each sample was examined by Western blot for
      phosphorylation levels of vasodilator-stimulated phosphoprotein (VASP), an
      abundant cAMP-dependent kinase substrate in platelets, and by the optical
      aggregometer for ADP- and collagen-induced aggregation, before and after 8 nmol/L
      prostaglandin E(1) (PGE(1)) treatment. Cilostazol intake did not affect VASP
      phosphorylation levels or the maximal aggregation rates without PGE(1) treatment.
      However, cilostazol intake apparently enhanced PGE(1)-induced VASP
      phosphorylation and PGE(1)-mediated reduction of ADP-and collagen-induced maximal
      aggregation rates. Levels of VASP phosphorylated at Ser157 were correlated and
      the maximal aggregation rates induced by ADP were inversely correlated with
      cilostazol concentrations in the plasma. CONCLUSION: The antiplatelet effects of
      cilostazol intake could be evaluated by measuring VASP phosphorylation levels and
      maximal aggregation rates in platelets by ex vivo treatment with a low
      concentration of PGE(1).

PMID- 18832778
TI  - Risk stratification of chronic heart failure patients by multiple biomarkers:
      implications of BNP, H-FABP, and PTX3.
AB  - BACKGROUND: B-type natriuretic peptide (BNP), heart-type fatty acid-binding
      protein (H-FABP), and pentraxin 3 (PTX3) each predict adverse cardiac events in
      chronic heart failure (CHF) patients. For prognostic evaluation from different
      aspects, the utility of combined measurement of the 3 biomarkers in patients with
      CHF was examined in the present study. METHODS AND RESULTS: Levels of BNP
      (associated with left ventricular dysfunction, positive if >200 pg/ml), H-FABP
      (marker of myocardial damage, positive if >4.1 ng/ml), and PTX3 (marker of
      inflammation, positive if >4.0 ng/ml) were measured in 164 consecutive CHF
      patients, and patients were prospectively followed with endpoints of cardiac
      death or rehospitalization. When patients were categorized on the basis of the
      number of elevated biomarkers, patients with 1, 2, and 3 elevated biomarkers had
      a 5.4-fold (not significant), 11.2-old (p<0.05), and 34.6-fold increase (p<0.01),
      respectively, in the risk of adverse cardiac events compared with those without
      elevated biomarkers. Kaplan-Meier analysis revealed that patients with 3 elevated
      biomarkers had a significantly higher cardiac event rate than patients with a
      lower number of elevated biomarkers. CONCLUSION: The combination of these 3
      biomarkers could reliably risk-stratify CHF patients for prediction of cardiac
      events.

PMID- 18832779
TI  - Multicenter prospective investigation on efficacy and safety of carperitide as a
      first-line drug for acute heart failure syndrome with preserved blood pressure:
      COMPASS: Carperitide Effects Observed Through Monitoring Dyspnea in Acute
      Decompensated Heart Failure Study.
AB  - BACKGROUND: Recently, vasodilators have been increasingly being recognized as
      useful for the treatment of acute heart failure syndromes (AHFS). Although
      carperitide (alpha-human atrial natriuretic peptide) has vasodilatory, diuretic
      and organ-protective effects, its efficacy and safety for the first-line drug
      treatment of AHFS have not been reported. METHODS AND RESULTS: A prospective
      observational study was performed in AHFS patients with preserved systolic blood
      pressure (SBP >or=120 mmHg), pulmonary congestion and dyspnea who were receiving
      carperitide monotherapy. The analysis was conducted in 1,832 patients (male:
      52.7%; mean age: 75.1+/-12.7 years). The initial SBP was 151.1+/-25.7 mmHg; 62.0%
      were diagnosed as having acutely decompensated chronic heart failure and 78.8%
      were assessed as functional class III-IV according to New York Heart Association
      classification. Carperitide was administered at an initial dosage of 0.025-0.05
      microg x kg(-1) x min(-1) in 50.4% of patients. In 1,524 patients (83.2%),
      carperitide monotherapy restored the acute phase and improved the degree of
      dyspnea as assessed using the modified Borg scale. The incidence of adverse drug
      reactions was 4.64%; the most frequently reported adverse reaction was
      hypotension (3.55%). CONCLUSION: In the present study, following carperitide
      monotherapy, 83.2% of AHFS patients recovered from the acute phase. Based on
      these findings, carperitide seems useful for the first-line drug treatment of
      AHFS in patients with pulmonary congestion and preserved blood pressure.

PMID- 18832780
TI  - Use of frequency domain analysis of skin conductance for evaluation of mental
      workload.
AB  - A specially designed mental task was performed by 16 subjects for frequency
      domain analysis of skin conductance (SC) to evaluate mental workload. The task
      was to memorize target letters, detect them within a 4 x 4 alphabet arrangement,
      and answer whether the number of targets contained in the arrangement
      corresponded to a randomly displayed number. As the number of target letters
      increased, the score for the card-sort NASA Task Load Index (CSTLX) and task
      performance increased significantly. The traditional parameter for the number of
      transient wave forms of SC response (SCR) and the height of its wave did not show
      any significant effect of task difficulty. In addition, SCRs were subjected to
      Fourier transformation and integration of the spectrum from 0.03 to 0.5 Hz. This
      frequency domain analysis enabled detection of small differences in mental
      workload that could not be detected by traditional amplitude domain analysis.
      Frequency-based analysis enables easy processing of physiological signals and is
      very effective in evaluating mental stress using SC recorded under actual
      environmental conditions such as the driving of a vehicle.

PMID- 18832781
TI  - Pedometer-determined physical activity and indicators of health in Japanese
      adults.
AB  - Recently, many cross-sectional studies observed that body mass index (BMI) and
      percentage of body fat (%BF) were inversely associated with pedometer-determined
      physical activities, but studies on Asian populations, including the Japanese,
      are sparse. Height, weight, body fat percentage (%BF, bioelectrical impedance
      analyzer), and waist circumference were measured on 117 women (62.8+/-4.5 years,
      22.2+/-2.2 kg/m(2)) and 62 men (64.0+/-4.6 years, 23.6+/-2.5 kg/m(2)). Pearson
      correlations and partial correlation coefficients after controlling for age were
      calculated between steps/day and variables. Furthermore, participants were
      classified into four groups as follows: <5,000, 5,000-7,499, 7,500-9,999, and
      >or=10,000 steps/day, and analyzed using ANOVA across activity groups. In women,
      a significant correlation was found between steps/day and BMI (r=-0.217,
      p=0.018), %BF (r=-0.292, p=0.0014), and the relationship was still significant
      after controlling for age. The relationship between steps/day and waist
      circumference was not significant. In men, a significant relationship was not
      observed between steps/day and obesity indices. The correlations between
      steps/day and both BMI and %BF were significant in Japanese women, but weak
      compared with Caucasian and African-American women as reported previously. A
      possible cause is racial difference in degree of obesity and body shape. The
      effects of physical activity on body shape and composition may differ according
      to race.

PMID- 18832782
TI  - ROC analysis of subcutaneous adipose tissue topography (SAT-Top) in female
      coronary heart disease patients and healthy controls.
AB  - The aim of this study was to investigate whether subcutaneous adipose tissue
      topography (SAT-Top) is different in female CHD patients (n=26) and healthy
      controls (n=36) matched to age, body size, weight, and BMI. The thicknesses of
      SAT layers were measured by LIPOMETER at 15 specified body sites. To calculate
      the power of the different body sites to discriminate between CHD women and
      healthy controls, receiver operating characteristic (ROC) curve analysis was
      performed. For each parameter, sensitivity and specificity were calculated at
      different cutoff points. CHD women showed a significant decrease to 78.36%
      (p=0.012) at body site 11-front thigh, 73.10% (p=0.012) at 12-lateral thigh,
      72.20% (p=0.009) at 13-rear thigh, 66.43% (p<0.001) at 14-inner thigh, and 49.19%
      (p<0.001) at 15-calf. The best discriminators analysed by ROC curves between
      female CHD patients and healthy controls turned out to be calf and inner thigh
      (optimal cut off values: calf: 3.85 mm and inner thigh: 11.15 mm). Stepwise
      discriminant analysis identified the body sites calf, lateral chest, and inner
      thigh as significant. In conclusion, information was obtained on the extent to
      which SAT thickness at each measured body site is able to discriminate between
      the two subject groups. The good discrimination results obtained for the present
      dataset are encouraging enough to recommend applying LIPOMETER SAT-Top
      measurements in further studies to investigate individual risks for CHD.

PMID- 18832783
TI  - Power spectrum entropy of acceleration time-series during movement as an
      indicator of smoothness of movement.
AB  - We propose a novel indicator for smoothness of movement, i.e., the power spectrum
      entropy of the acceleration time-series, and compare it with conventional indices
      of smoothness. For this purpose, nineteen healthy adults (21.3+/-2.5 years old)
      performed the task of raising and lowering a beaker between the level of the
      umbilicus and eye level under the two following conditions: one with the beaker
      containing water and the other with the beaker containing a weight of the same
      mass as the water. Moving the beaker up and down when it contained water required
      extra control to prevent the water from being spilled. This means that movement
      was not as smooth as when the beaker contained a weight. Under these two
      conditions, entropy was measured along with a traditional indicator of smoothness
      of movement, the jerk index. The entropy could distinguish just as well as the
      jerk index (p<0.01) between when water was used and when the weight was used. The
      entropy correlated highly with the jerk index, with Spearman's rho at 0.88
      (p<0.01). These results showed that the entropy derived from the spectrum of the
      acceleration time-series during movement is useful as an indicator of the
      smoothness of that movement.

PMID- 18832784
TI  - Characteristics and lateral dominance of hand grip and elbow flexion powers in
      young male adults.
AB  - This study aimed to clarify the characteristics and the lateral dominance of hand
      grip power and elbow flexion power. The subjects were 15 healthy young males
      (mean age 22.1+/-0.7 yr, mean height 171.3+/-3.4 cm, mean mass 64.5+/-4.1 kg).
      All subjects were right-handed. Peak power was measured by both hands with 6
      different loads of 20%-70% of maximum voluntary contraction. The maximum
      voluntary contraction of hand grip movement and elbow flexion movement was
      significantly larger in the dominant hand. Peak power of the dominant hand was
      larger in all loads in hand grip movement and in loads of 20% and 30% of maximum
      voluntary contraction in elbow flexion movement. In short, lateral dominance was
      confirmed. Peak power was significantly larger in hand grip movement than in
      elbow flexion movement in both hands. Peak velocity decreased with increasing
      loads in both movements, but peak power increased until about 50% of maximum
      voluntary contraction and then decreased. The peak power ratio of the dominant
      hand to the nondominant hand was significantly larger in hand grip movement than
      in elbow flexion movement in all loads and the peak power ratio in elbow flexion
      movement was more marked in light loads. In conclusion, both powers showed
      lateral dominance. Lateral dominance is more marked in hand grip power.

PMID- 18832785
TI  - Sex and age differences of relationships among stepping parameters for evaluating
      dynamic balance in the elderly.
AB  - This study aimed to examine the relationships among various stepping parameters,
      sex, and age in the elderly. Healthy elderly Japanese individuals 60-85 years old
      (50 males and 61 females) performed 4 types of stepping motions for 20 s.
      Stepping motions included bilateral stepping (back/forth and right/left) and
      unilateral stepping (back/forth and right/left). The number of steps, the average
      connecting time of a foot during one step, and the average time of both feet
      touching the floor at the same time (bilateral connecting time) were measured
      with a foot switch sheet. The trial-to-trial reliability was very high (above
      0.86) except for the bilateral connecting time in the bilateral stepping
      back/forth test for 70-85 year olds (males: 0.67, females: 0.68). With age, the
      number of steps was significantly smaller, and the average connecting time and
      the bilateral connecting time were shorter in all stepping tests. There were
      significant sex differences in bilateral connecting time for bilateral stepping
      right and left and the number of steps for the bilateral stepping back and forth
      and the unilateral stepping right and left tests. The number of steps and average
      connecting time showed high correlations between bilateral stepping right/left
      and back/forth (r=0.71-0.94) and between unilateral stepping back/forth and
      right/left (r=0.87-0.99). There were significant correlations of the average
      connecting time between bilateral and unilateral stepping motions (r=0.51-0.83),
      but both stepping motions are considered to have different motion properties from
      the viewpoint of center of gravity sway. The correlations between the bilateral
      connecting time and the number of steps in bilateral stepping were relatively low
      (males: /r/<0.70, females: /r/<0.57). The bilateral connecting time was near 0 s
      in many males; thus, it may depend greatly on individual or sex differences in
      stepping strategy. These results suggest that the stepping motions used in this
      study can evaluate dynamic balance ability, and that the unilateral test may be
      useful for the elderly who cannot walk independently with ease.

PMID- 18832786
TI  - A single bout of moderate-intensity exercise increases vascular NO
      bioavailability and attenuates adrenergic receptor-dependent and -independent
      vasoconstrictor response in rat aorta.
AB  - The present study investigated the effect of one bout of moderate-intensity
      exercise on the adrenergic receptor-dependent and -independent vasoconstrictor
      response in rat aortas, and the role of nitric oxide (NO) bioavailability on
      these vasomotor responses. One group of rats was submitted to a 60 min of
      exercise at approximately 60% of maximal exercise capacity on a treadmill
      (exercise group) and the other one was placed in the treadmill without running
      (control group). Immediately after this period, both groups were euthanized and
      the thoracic aorta was removed to evaluate the vasoconstrictor response to
      norepinephrine and potassium chloride, and to evaluate the vascular nitrite and
      nitrate concentration. One bout of exercise attenuated the maximal contractile
      response to both norepinephrine and potassium chloride compared to control group.
      These differences on vascular reactivity were not observed in endothelium-denuded
      aortic rings and aortic rings pre-incubated with a nitric oxide synthesis
      inhibitor. Additionally, exercise group increased NO bioavailability (nitrite and
      nitrate concentration) as compared to control group. These results demonstrate
      that one bout of moderate-intensity exercise is able to attenuate adrenergic
      receptor-dependent and -independent vasoconstrictor response in rat aorta, mainly
      by increasing vascular NO bioavailability.

PMID- 18832787
TI  - Postoperative reorganization of gastric pacemaker activity in patients after an
      extended period following distal gastrectomy.
AB  - We recorded and analyzed electrogastrograms (EGGs) from 12 patients following
      distal gastrectomy. The EGGs were recorded from between 3 and 262 months post
      operatively. Gastric electrical activity, which showed a distinct repeating
      pattern with a frequency of 3 cycles per minute (cpm), was easily recognizable in
      subjects who were recorded 16-20 years postoperatively, but was not clearly
      evident in EGG running spectra of subjects with a shorter postoperative period.
      Although the postprandial instability factor of the 3-cpm components (standard
      deviation of mean spectral frequency of peak 3-cpm group/mean of the 3-cpm
      spectral frequency) of the epigastric and supraumbilical EGGs showed a
      significant negative linear correlation with postoperative months, no such
      correlation was seen in the postprandial to fasting power ratio (postprandial
      power / fasting power) of the 3-cpm activity component. Therefore, we
      hypothesized that the disorganized pacemaker activity of the remnant stomach
      following distal gastrectomy can be reorganized to work as a synchronized unit
      over a long postoperative recovery period of from 15 to 20 years. A greater
      degree of epigastric and supraumbilical fasting 6-cpm power seemed to result in a
      worse quality of life (QOL). Similarly, a larger ratio of the supraumbilical
      postprandial to fasting power ratio of the 6-cpm activity seemed to result in a
      worse QOL. In contrast a larger ratio of the infaraumbilical postprandial to
      fasting power content of the 6-cpm activity seemed to result in a better QOL.

PMID- 18832788
TI  - Inhibition of antigen-induced bronchial smooth muscle hyperresponsiveness by
      lovastatin in mice.
AB  - Statins have been proposed as a novel treatment of respiratory diseases. To
      determine the beneficial effects of statins on the airway hyperresponsiveness, a
      characteristic feature of allergic bronchial asthma, the effect of systemic
      treatment with lovastatin on antigen-induced bronchial smooth muscle
      hyperresponsiveness was investigated in mice. Male BALB/c mice were sensitized
      and repeatedly challenged with ovalbumin antigen. Animals were also treated with
      lovastatin (4 mg/kg/day, i.p.) once a day prior to and during the antigen
      inhalation period. The bronchial smooth muscle responsiveness to acetylcholine,
      but not to high K(+)-depolarization, was markedly and significantly augmented in
      the repeatedly antigen challenged mice. The bronchial smooth muscle
      hyperresponsiveness to acetylcholine induced by antigen exposure was
      significantly attenuated by the systemic treatment with lovastatin. Thus,
      lovastatin might have therapeutic potential to ameliorate airway
      hyperresponsiveness in allergic bronchial asthma.

PMID- 18832790
TI  - Diabetes mellitus and responses of the urinary bladder to acetylcholine: an in
      vitro study.
AB  - This study was prompted by the inconsistent reports and apparent controversies
      that exist in the biomedical literature on the responses of diabetic bladder
      strips to cholinergic nerve stimulation or exogenously-administered muscarinic
      agonists, especially acetylcholine (ACh). In the present study, acetylcholine
      induced contractions of urinary bladders isolated from normoglycaemic (normal)
      and streptozotocin-treated, diabetic Wistar rats were examined under
      physiological conditions. Mechanical contractile changes of the isolated urinary
      bladders of STZ-treated, diabetic rats in response to bath-applied acetylcholine
      were compared with those obtained from isolated urinary bladders of normal, age
      matched, control rats. Results obtained show that urinary bladders from diabetic
      rats were always more spontaneously active after mounting, than those of the age
      matched normal, control rats. ACh (10(-8)-10(-4) M) provoked concentration
      related, atropine-sensitive contractions of the isolated urinary bladders of both
      diabetic and age-matched normal, control rats. However, acetylcholine always
      induced more powerful and greater contractions of the diabetic bladders compared
      with bladders from the age-matched normal, control rats. The magnitude and/or
      intensity of the diabetic bladder enhanced contractile responses to ACh continued
      to increase as the diabetic state of the animals progressed.

PMID- 18832789
TI  - The possible involvement of hyperpolarizing mechanisms in histamine-induced
      relaxation of the rat portal vein.
AB  - The present study evaluated the effects of histamine 10(-2) M on longitudinal
      preparations of rat portal vein. It was observed that histamine 10(-2) M induced
      relaxation of rat portal vein preparations pre-contracted with phenylephrine 10(
      4) M. On the other hand, no pharmacological effects were observed in preparations
      not pre-contracted. The observed histamine-induced relaxing effect was absent in
      preparations pre-contracted with KCl (120 mM) or in the presence of depolarizing
      nutritive solution. However, the histamine-induced relaxation was still present
      in the endothelium-removed preparations. The histamine-induced relaxation also
      was not prevented by astemizole (10(-6) M, 10(-5) M and 10(-4) M), cimetidine
      (10(-5) M, 10(-4) M and 10(-3) M) or thioperamide (10(-6) M, 10(-5) M and 10(-4)
      M), selective antagonists H(1), H(2) and H(3), respectively. The presence of L
      NAME 10(-4) M or L-NAME 10(-4) M plus indomethacin 10(-5) M also did not prevent
      the histamine-induced relaxation observed in rat portal vein. Thus, the histamine
      induced relaxation observed in rat portal vein appears to involve a non
      endothelial hyperpolarizing mechanism independent of H(1), H(2) and H(3)
      receptors.

PMID- 18832791
TI  - Cardiac diastolic dysfunction is associated with cerebral white matter lesions in
      elderly patients with risk factors for atherosclerosis.
AB  - Cerebral white matter lesions on magnetic resonance imaging (MRI) are considered
      to be the result of brain ischemic injury and a risk factor for clinical stroke.
      The purpose of this study was to elucidate the relationship between the cardiac
      diastolic function and cerebral white matter lesions in elderly patients with
      risk factors for atherosclerosis. The study subjects were 55 patients (75 +/- 7
      years) with risk factors for atherosclerosis including hypertension, diabetes
      mellitus, and dyslipidemia. Patients with symptomatic cerebrovascular events were
      excluded from the study. Cerebral white matter lesions, which were defined as
      exhibiting high intensity regions on brain MRI, were evaluated with the degrees
      of periventricular hyperintensity (PVH) according to the Japanese Brain Dock
      Guidelines of 2003. Peak early diastolic mitral annular velocity (E' velocity)
      was measured by tissue Doppler echocardiography, and was used as a parameter of
      cardiac diastolic function. The mean value of E' velocity was decreased due to
      the cardiac diastolic dysfunction (5.2 +/- 1.4 cm/s). In addition, the E'
      velocity was inversely correlated with the degree of PVH (rho = -0.701, p <
      0.001). Stepwise regression analysis showed that the decrease in the E' velocity
      (beta coefficient = -0.42, p < 0.001) and the presence of hypertension (beta
      coefficient = 0.31, p = 0.001) were independent determinants of the degree of
      PVH. Thus, cardiac diastolic dysfunction is correlated to the severity of
      cerebral white matter lesions, suggesting the cardio-cerebral connection in
      elderly patients with risk factors for atherosclerosis.

PMID- 18832792
TI  - Visual evoked potentials in differential diagnosis of multiple sclerosis and
      neurobehcet's disease.
AB  - Behcet's disease, a multisystemic vascular inflammatory disorder of unknown
      origin, is relatively rare and central nervous system involvement is seen in 5%
      of affected individuals. This form of the disease, called as neurobehcet's
      disease (NB), can be misdiagnosed as multiple sclerosis (MS), a demyelinating
      disorder of central nervous system, so their differential diagnosis is important.
      In this study, to identify the parameters of electrophysiological testing that
      might be useful in their differential diagnosis, we performed evoked potentials
      (EPs) and electroneuromyography (ENMG) on patients with MS and NB, and on normal
      volunteers. A total of 95 persons, 55 MS patients, 20 NB patients and 20 normal
      volunteers between ages 31 and 55, were studied electrophysiologically. Visual
      evoked potential (VEP), brainstem auditory evoked potential (BAEP), posterior
      tibial somatosensory evoked potential (SEP) and nerve conduction and needle
      electromyography studies were performed on all patients and volunteers. All
      parameters of EPs were compared among the groups. The results of the BAEP and SEP
      studies did not show statistically significant difference between NB and MS.
      However, the VEP study indicated that the amplitude values of cortical VEP
      potentials (P100) in the NB and MS groups were lower than those of the normal
      group (p < 0.01), and that the amplitudes in the NB group were lower than for the
      MS group (p < 0.05). Therefore, P100 amplitude measured from peak to peak seems
      to be more reliable and thus should be used in the differential diagnosis of MS
      and NB.

PMID- 18832793
TI  - Granulocyte-colony stimulating factor inhibits neuronal apoptosis in a rat model
      of diabetic cerebral ischemia.
AB  - Incidence of cerebral vascular disease (CVD) is higher in patients with diabetes
      mellitus (DM) than that in individuals without DM, and neuronal apoptosis
      determines the severity of cerebral infarction. However, there is no effective
      therapy for CVD. Granulocyte-colony stimulating factor (G-CSF), a potent
      hematopoietic factor, could inhibit apoptosis of hematopoietic progenitor cells.
      However, its effect on neuronal cells is still unclear. In this study, we
      investigated the anti-apoptosis properties of G-CSF in neurons following focal
      cerebral ischemia in diabetic rats. The diabetic condition was generated in rats
      by intravenous injection of streptozotocin. After 6 weeks, diabetic rats
      underwent middle cerebral artery occlusion (MCAO) and received subcutaneous
      administration of G-CSF (50 microg/kg) daily for 7, 14 or 21 days. We analyzed
      the changes in neurological severity scores, infarct volume, number of apoptotic
      neurons, and the expression of G-CSF receptor, phosphorylated signal transducer
      and activator of transcription 3 (pSTAT3), cellular inhibitor of apoptosis
      protein 2 (cIAP2), Bcl-2, and Bax in the brain tissue. Bax is a pro-apoptotic
      member of the Bcl-2 protein family. The DM rats treated with G-CSF not only
      showed the reduced infarct volume and decreased apoptosis cell number, but also
      presented improved neurological scores. The G-CSF also increased the expression
      of pSTAT3, Bcl-2, and cIAP2 proteins as well as Bcl-2 mRNA, but inhibited Bax
      protein expression in the brain. These results indicate that G-CSF partially
      increases neuronal survival by affecting apoptosis pathways. G-CSF provides a
      potential treatment for stroke and other neurological dysfunction accompanied by
      neuronal apoptosis.

PMID- 18832794
TI  - Enhancement of glucose toxicity by hyperbaric oxygen exposure in diabetic rats.
AB  - The side effects of hyperbaric oxygen (HBO) treatment, such as oxidative stress
      and oxygen toxicity, have long been of interest. However, there are no
      comprehensive studies evaluating such toxic effects in diabetes mellitus (DM).
      The purpose of this study was to determine the effects of HBO on glucose
      homeostasis and histological changes in pancreatic beta-cells of experimentally
      induced diabetic rats. A total of 24 male Wistar rats were randomly divided into
      4 groups: 1) Control group, no diabetic induction without HBO treatment; 2) HBO
      group, exposed to 100% oxygen at 2.8 ATA (atmosphere absolute) for 2 h once
      daily, for 7 days; 3) DM group, diabetes induced by streptozotocin (STZ)
      injection; and 4) DM + HBO group, received both STZ injection and HBO exposure.
      HBO treatment, with clinically recommended pressures and duration of therapy, was
      started on day 5 after STZ injection, when the blood glucose levels were
      significantly increased. After the last HBO treatment, the pancreatic tissues
      were immunostained to measure the areas of insulin immunoreactive beta-cells in
      the islets of Langerhans. The blood glucose increased significantly following
      exposure to HBO, with the highest levels achieved in rats, which had been treated
      with both HBO and diabetic induction. The area populated with insulin
      immunoreactive beta-cells decreased significantly following diabetic induction
      and/or HBO exposure, with the smallest area in DM + HBO group. Thus, HBO exposure
      enhanced the cytotoxic effect of STZ in the beta-cells of the pancreas. HBO
      should be cautiously employed in diabetic patients.

PMID- 18832795
TI  - Nonrecurrent inferior laryngeal nerve without vascular anomaly as a genuine
      entity.
AB  - Inferior laryngeal nerve (ILN), which usually arises from vagus nerve, runs
      recurrent course and is called recurrent ILN (RILN). Intimate knowledge of normal
      and anatomic variants of the ILN reduces the risk of nerve injury and vocal cord
      paralysis in thyroid and parathyroid surgery. The nonrecurrent ILN (NRILN) is a
      rare nerve anomaly that is associated with a right aberrant subclavian artery. We
      encountered 2 patients with NRILN during thyroid surgery. Patient 1, a 57-year
      old woman, had mediastinal thyroid tumor without vascular anomaly. Patient 2, a
      47-year-old woman with a history of esophageal foreign body (fish bone), was
      suspected to have NRILN with vascular anomaly before surgery, as judged by
      preoperative enhanced CT. In the patient 1, we verified laryngeal mobility
      function of the NRILN by nerve stimulation, and confirmed the absence of RILN in
      usual recurrent course. The findings in the patient 1 indicate that NRILN without
      subclavian artery anomaly is a genuine entity. In both patients we performed
      thyroid surgery safely and fast by expectation and identification of NRILN by use
      of nerve stimulator. In conclusion, we confirm the existence of NRILN without
      vascular anomaly and show effectiveness of preoperative enhanced CT and valuable
      use of nerve stimulator for nerve preservation in the patients with NRILN.

PMID- 18832796
TI  - Growth inhibitory effect of the ternary complex factor Net on human pancreatic
      carcinoma cell lines.
AB  - Pancreatic carcinoma is one of the most aggressive malignancies and carries the
      most dismal prognoses of all cancers. A better understanding of the genes
      involving in tumor development may allow us to tackle this rapidly progressive
      disease. The Net gene belongs to the ternary complex transcription factor (TCF)
      family and is regulated by the Ras/mitogen-activated protein kinase-signaling
      pathway. Under basal conditions, Net shows strong repressing function on
      transcription of proto-oncogene gene c-fos. Moreover, the lower expression of Net
      has been noted in some carcinoma cells, such as cervical cancer. To study the
      effect of Net on c-fos expression and its potential role in the growth of
      pancreatic carcinoma, we developed a recombinant plasmid, a pEGFP-N1-Net, which
      codes for Net-EGFP fusion proteins, and stably transfected it into BxPC-3 human
      pancreatic carcinoma cells. Using stable transformants, we were able to show that
      overexpression of Net decreased the expression of c-fos and inhibited pancreatic
      cancer cell proliferation. Cell cycle analysis demonstrated that Net
      overexpression inhibited cell cycle progression. These findings suggested that
      loss of Net repression could augment c-fos expression and further trigger
      neoplastic cell proliferation, which was involved in the pathogenesis of
      pancreatic cancer. Therefore, Net might be a potential target for the treatment
      of c-fos-positive pancreatic cancer.

PMID- 18832797
TI  - Differentiation of adipose-derived stromal vascular fraction culture cells into
      chondrocytes using the method of cell sorting with a mesenchymal stem cell
      marker.
AB  - The incidence of arthritic diseases is rapidly increasing in most advanced
      countries. Articular cartilage, which is the most important tissue in the joint,
      consists of chondrocytes and abundant extracellular matrix, including aggrecan,
      and shows poor self-repair. We studied the potential of stem cells in mouse
      subcutaneous adipose tissue as a source of cells to regenerate cartilage tissue.
      Analysis of adipose-derived stromal vascular fraction culture cells (ADSVFs)
      using mesenchymal stem cell markers showed that CD90-positive cells accounted for
      93.8%, CD105-positive cells for 68.5%, and p75 neurotrophin receptor (p75NTR,
      CD271)-positive cells for 36.1%. These results indicate that cells positive for
      mesenchymal stem cell markers are present in ADSVFs. The CD105-positive or 
      negative cells were isolated from ADSVFs by magnetic cell separation (MACS), and
      the efficiency of differentiation into chondrocytes was compared with using three
      methods of pellet method, gel-coating method, and gel-embedding sheet method.
      Using the CD105-positive cells and the gel-embedding sheet method, aggrecan mRNA
      was detected about three times higher than pellet and gel-coating methods. The
      above data suggest that ADSVFs could be differentiated into chondrocyte-like
      cells in the gel-embedding sheet method and could be useful in regenerative
      medicine to treat cartilage defects or cartilage degenerative disease. The use of
      cells sorted by mesenchymal stem cell markers from adipose tissue would gain
      position in the repair of cartilage tissue.

PMID- 18832798
TI  - Physician and hospital characteristics related to length of stay for sudden
      sensorineural hearing loss patients.
AB  - The treatment of sudden sensorineural hearing loss (SSNHL) has remained one of
      the most controversial issues in otolaryngology, and there are wide disparities
      between clinicians' treatment methods for SSNHL. Using five-year population-based
      data, we explored the relationship between physician and hospital characteristics
      and the length of stay (LOS) for SSNHL patients in Taiwan. The dataset was
      derived from the National Health Insurance Research Database. The patients in the
      study sample were identified by a principal diagnosis of sudden hearing loss. A
      total of 8712 hospitalization cases between 1998 and 2002 inclusive were
      included. Multiple regression analyses were performed in order to explore the
      relationship between physician and hospital characteristics and LOS, adjusting
      for patients' age and gender, as well as complications or comorbidities. The mean
      LOS for the duration of the study period was 5.62 days, while the regression
      analysis showed that, as compared to district hospitals, the LOS in medical
      centers and regional hospitals was 0.42 and 0.37 days longer, respectively (all p
      < 0.001). The analysis also revealed that the LOS was 0.71 days shorter for
      patients who were attended by physicians specializing in otolaryngology than for
      those attended by physicians specializing in other areas (p < 0.001). This study
      concludes that there is indeed a relationship between physician and hospital
      characteristics and the LOS for SSNHL patients. The results of this study serve
      to highlight the importance of developing treatment protocols for SSNHL so as to
      reduce the variation in physician or hospital behavior.

PMID- 18832799
TI  - Increased nuclear expression of growth hormone receptor in uterine cervical
      neoplasms of women under 40 years old.
AB  - There has been an increased incidence of cervical cancer among young women, and
      they tend to have a poor prognosis due to unknown reasons. We hypothesize growth
      hormone (GH) receptor (GHR) may be involved in the proliferation of cervical
      carcinoma, because GH-related neoplasms arise in various organs and the amount of
      GH secretion may be different according to age. GHR is normally expressed in the
      cell membrane and cytoplasm, while the nuclear distribution of GHR has been
      considered to reflect high proliferative activity of cells. We analyzed the
      subcellular localization of GHR by immunohistochemistry in cervical neoplasms of
      55 patients (38.6 +/- 13.9 years old): 33 patients (< 40 years) and 22 patients
      (>or= 40 years). Nuclear expression of GHR was detected in more than 50% of
      neoplastic cells present in the tissue samples derived from 20 patients under 40
      years (20/33, 61%), whereas less than 25% of neoplastic cells expressed GHR in
      their nuclei in 17 patients over 40 years (17/22, 77%). In contrast, more than
      75% of neoplastic cells showed cytoplasmic GHR expression in the tissues derived
      from both age groups. Furthermore, the population of cells with nuclear GHR
      expression was high in the squamous epithelium and the stromal cells of patients
      under 40, but low in patients over 40. The GH-GHR signal may act at the nuclear
      level to promote the proliferation of uterine cervical neoplasms in young
      patients. We suggest the involvement of GHR in progression of uterine cervical
      carcinoma.

PMID- 18832800
TI  - Components of social capital and socio-psychological factors that worsen the
      perceived health of Japanese males and females.
AB  - Social capital refers to the quantity and quality of social relationships, such
      as formal and informal social connections as well as norms of reciprocity and
      trust that exist in a place or a community. This article analyzed the data from
      Japan 2004 B Survey in order to elucidate the effects of social capital and socio
      psychological factors on the health of Japanese males and females. The Survey was
      a part of a nationwide random study on Japanese national character, which has
      been conducted by the Institute of Statistical Mathematics since 1953. A total of
      785 (372 males and 413 females) valid data from 1,200 adult samples were used.
      Logistic regression analysis showed that the self-reported symptoms were
      increased by negative attitude to generalized trust in males, and by negative
      attitude to norm of reciprocity in females. Moreover, in females, health
      dissatisfaction was enhanced by low perceptions of support. In both genders, self
      reported symptoms and health dissatisfaction were worsened by anxiety. The self
      reported symptoms were increased by an adherence to religion and spirituality in
      males, whereas in females, the health dissatisfaction increased with low income
      and a concern about superstitions. Thus, from a viewpoint of social capital,
      perceived health is susceptible to personal relationships in females and to
      distrust in males. Anxiety seems a key factor affecting perceived health. In
      addition, females are influenced by economic status and superstitions, whereas
      males are more concerned about religion or the mind in relation to health. These
      findings are useful in developing health policies for Japanese.

PMID- 18832801
TI  - Lower mortality in male physicians of Chinese medicine than male population in
      Taiwan.
AB  - Studies on the physicians' health have paid less attention on the Chinese
      medicine than on the western medicine professionals. Like western medicine
      professionals, Chinese medicine physicians' health condition is critical to the
      quality of care and patients' safety. They also cared a large number of patients
      in many Asia societies. However, no data have been reported regarding the health
      problems associated with Chinese medicine physicians. The aim of this study was
      to examine the mortality patterns of a cohort consisting of 6109 male physicians
      of Chinese medicine who were followed from 1991 through 2003 in Taiwan. The
      analyses of female subjects were not included due to small sample size. We
      calculated the overall and cause-specific standardized mortality ratios (SMRs)
      and life expectancy of the study cohort using the death rates of some 11 millions
      of Taiwanese male population as reference. We found out that physicians of
      Chinese medicine experienced significantly lower death rate of mortality from all
      causes (SMR = 0.63, 95% > CI: 0.57, 0.69), from malignant neoplasms (SMR = 0.69,
      95% CI: 0.57, 0.82) and from cerebrovascular disease (SMR = 0.53, 95% CI: 0.38,
      0.72). Additionally, they have longer life expectancy (ranged from 3 years to
      approximately 15 years). Our study is crucial to evaluate potential health risks
      associated with Chinese medicine physicians. Although this study did not reveal
      elevated death rate among Chinese medicine physicians, researchers and policy
      makers should not overlook other heath problems that Chinese medicine physicians
      might have experienced.

PMID- 18832802
TI  - Insulin modulation of luteinizing hormone secretion in normal female volunteers
      and lean polycystic ovary syndrome patients.
AB  - BACKGROUND/AIMS: Endocrine features of polycystic ovary syndrome (PCOS) include
      altered ovarian steroidogenesis, hyperinsulinemia and abnormal luteinizing
      hormone (LH) secretion. This study was undertaken to further evaluate the role of
      insulin to modulate LH secretion in lean PCOS patients with normal insulin
      sensitivity and normal volunteers. METHODS: The study was performed in five
      nonobese patients diagnosed with PCOS on the basis of amenorrhea and a polycystic
      morphology at ovarian ultrasound, and 5 normal controls in early to mid
      follicular phase and matched for weight and age. All subjects were phenotyped,
      and then admitted for 12 h of frequent (q 10') blood sampling on two separate
      occasions, once for a baseline study and the other time for a hyperinsulinemic
      and euglycemic clamp study. LH was measured in samples obtained throughout each
      admission in order to perform LH pulse analysis. RESULTS: Baseline LH secretion
      in PCOS subjects was significantly different from controls: they had higher LH
      levels, higher LH/FSH ratios as well as a faster LH pulse frequency than normal
      women. Insulin administration did not affect the pattern of LH secretion of PCOS
      patients, whereas it significantly increased the LH pulse frequency while
      decreasing the LH interpulse intervals in the controls. CONCLUSIONS: These data
      confirm that an abnormal pattern of LH secretion characteristic of PCOS can be
      observed in lean patients, and appears independent of peripheral insulin levels.
      Furthermore, our results in lean controls provide the first direct evidence that
      peripheral insulin can modulate the activity of hypothalamic gonadotropin
      releasing hormone (GnRH) neurons in the human.

PMID- 18832803
TI  - An unexpected cause of bilateral hemothorax.

PMID- 18832804
TI  - Selective depletion of alveolar macrophages in polymicrobial sepsis increases
      lung injury, bacterial load and mortality but does not affect cytokine release.
AB  - BACKGROUND: Resident tissue macrophages exert important functions during severe
      systemic infection and contribute to changes in local as well as systemic immune
      responses. Alveolar macrophages (AM) play a crucial role in airway diseases and
      in the defense against microorganisms invading the body via the bronchopulmonary
      tract. It has been postulated that AM are involved in the development of acute
      local disorders as a consequence of extrapulmonary stimuli like pancreatitis,
      peritonitis, or trauma. OBJECTIVE: The aim of this study was to analyze the local
      and systemic role of AM during sepsis using selective AM depletion in the murine
      colon ascendens stent peritonitis (CASP) model of polymicrobial sepsis. METHODS:
      48 h prior to CASP surgery, AM of female C57BL/6 mice were selectively depleted
      by intratracheal application of clodronate liposomes (Lipo-clod). For control
      purposes, phosphate-buffered saline (PBS) liposomes (Lipo-PBS) were used.
      RESULTS: CASP led to significantly elevated levels of local and systemic
      cytokines independent of the presence of AM. In contrast, levels of gut-derived
      bacteria in bronchoalveolar lavage and lung of septic mice were significantly
      higher in Lipo-clod-treated animals compared to Lipo-PBS-treated animals. After
      CASP-induced sepsis, local barrier dysfunction in the lung was detected; AM
      depletion resulted in severely enhanced development of acute lung injury.
      Consequently, Lipo-clod-treated animals showed strongly reduced survival rates
      after CASP. CONCLUSIONS: Contrarily to other macrophage populations, AM do not
      significantly contribute to local and systemic cytokine release during
      polymicrobial abdominal sepsis. AM have important protective functions for local
      clearance of gut-derived bacteria and attenuation of lung injury.

PMID- 18832805
TI  - Pituitary changes involved in prolactin secretion induced by mifepristone and
      naloxone during late pregnancy.
AB  - BACKGROUND/AIMS: The antiprogesterone mifepristone facilitates prolactin release,
      an effect enhanced by administration of the opioid antagonist naloxone. The
      present study explores ultrastructural changes in lactotropes after mifepristone
      and naloxone administration, correlating them with the expression of pituitary
      prolactin. METHODS/RESULTS: Rats were sacrificed at 18:00 h on day 19 of
      pregnancy. Prolactin immunoelectron microscopy of lactotropes from control rats
      showed characteristics of quiescent cells with numerous small and spherical
      secretory granules. Naloxone administration did not modify lactotrope morphology
      or prolactin expression in terms of mRNA or protein abundances. Mifepristone
      treatment induced lactotrope activation with development of the rough endoplasmic
      reticulum and Golgi complex with prolactin immunoreactive small newly formed and
      large mature secretory granules. Mifepristone increased prolactin mRNA and
      protein expression. Naloxone administration to mifepristone-treated rats
      potentiated lactotrope activation compared with mifepristone alone showing
      exocytotic images of prolactin granules and some cells with evident signs of
      involution. CONCLUSIONS: (1) Blockade of progesterone action by mifepristone
      activated the lactotrope, increased significantly prolactin mRNA and protein
      expression and prepared the pituitary for naloxone action. (2) The high serum
      prolactin levels induced by mifepristone and naloxone may regulate negatively
      lactotrope activity as suggested by the presence of regressing cells neighboring
      the actively secreting cells.

PMID- 18832806
TI  - Treatment of early stages of mycosis fungoides with narrowband ultraviolet B. A
      clinical, histological and molecular evaluation of results.
AB  - BACKGROUND: Narrowband ultraviolet B (UVB) phototherapy is increasingly used in
      mycosis fungoides (MF). OBJECTIVE: We report on the results obtained in a
      prospective series of early MF patients receiving this therapeutic regimen.
      METHODS: In total, 22 patients were treated. Therapeutic results were evaluated
      on clinical, histological and molecular levels. Patients were then submitted to a
      clinical follow-up. RESULTS: The cumulative number of treatments ranged from 22
      to 48 (mean: 29). A complete clinical remission (CCR) was obtained in 18/22
      patients, and a partial clinical remission in 4 cases. Complete or partial
      histological responses were achieved in 9/15 (all in CCR) and 4/15 patients,
      respectively. The molecular response was evaluated in 12 patients, and a
      disappearance of the dominant T cell clone in the skin was obtained in only 3
      cases. After 4-48 months of follow-up (mean 20.1 months), 7/18 patients in CCR
      (39%) relapsed. CONCLUSION: Narrowband UVB phototherapy is a well-tolerated
      treatment of early-stage MF, and its efficiency is maximal in very early stages
      (Ia). Even though clinical results seem very similar to PUVA through indirect and
      tentative comparisons with historical series, relapses tend to occur earlier than
      with PUVA, especially when an incomplete histological or molecular response was
      achieved.

PMID- 18832807
TI  - Completeness of histopathology reporting of melanoma in a high-incidence
      geographical region.
AB  - BACKGROUND: Appropriate histopathology reporting helps to ensure effective
      therapy and prognosis. OBJECTIVE: To examine compliance with clinical practice
      guidelines for histopathology reports of melanomas. METHODS: A sample of melanoma
      histopathology reports in Queensland was audited for inclusion of recommended
      information. The quality of documentation was constructed and multivariate
      analysis used to determine factors affecting the quality of reporting practices.
      RESULTS: Documentation of the most important features of melanoma was high: clear
      diagnosis (99.8%; 95% CI 98.6-100), thickness (99.8%; 95% CI 98.6-100), comment
      on adequacy of excision (87.9%; 95% CI 84.9-91.0) and measurement of margins
      (91.9%; 95% CI 88.8-91.4). Overall reporting of ulceration and regression was of
      lesser completeness (83.0 and 77.8%, respectively) and these features were more
      likely to be reported by high-volume laboratories (p < 0.001 and p = 0.037,
      respectively). This trend was not apparent for other features. Fewer than 50% of
      reports documented mitotic rate per square millimetre, predominant cell type,
      microsatellites, growth phase and desmoplasia. CONCLUSION: Awareness of current
      reporting practices and identification of areas in which insufficiencies exist
      enable the revision of systems and potential improvements to the transfer of
      information to treating clinicians.

PMID- 18832808
TI  - Discordant results with pimecrolimus 1% cream in the treatment of plasma cell
      balanitis.
AB  - Plasma cell balanitis of Zoon is a chronic, benign, inflammatory dermatosis of
      the glans penis and prepuce. The exact aetiology is unknown. The treatments
      described to date have provided only partially successful results. Recently,
      several reports of plasma cell balanitis successfully treated with calcineurin
      inhibitors have been published. We report 3 cases of plasma cell balanitis
      refractory to several treatments with steroids and antifungals treated with
      pimecrolimus 1% cream applied twice daily: 1 patient had a complete resolution, 1
      patient had a marked response but relapsed during the treatment and the last
      patient had a partial response due to the development of a side effect that
      precociously required to stop the treatment. One patient referred a slight
      pruritus after the first applications of the cream that spontaneously disappeared
      after a few minutes. Additional experiences are needed to determine if topical
      pimecrolimus is an effective and safe treatment for plasma cell balanitis.

PMID- 18832809
TI  - Spitz nevus: follow-up study of 8 cases of childhood starburst type and proposal
      for management.
AB  - Spitz nevus is an uncommon, benign melanocytic neoplasm that shares many clinical
      and histological features with melanoma. It presents clinical ambiguity that
      makes the diagnosis and management of the patient difficult. We present our
      experience in the management of Spitz nevus by rigorous dermoscopic long-term
      follow-up of 8 Spitz nevi in patients younger than 12 years. Dermoscopic images,
      acquired every 6 months, show evolution and modifications of these lesions. The
      aim of this paper is to better understand the long-term modifications of nevi
      with starburst pattern to avoid surgical excision of these lesions in the
      pediatric age group.

PMID- 18832810
TI  - 'Bowenoid wart': wart with bowenoid histological changes? Report of 9 cases.
AB  - INTRODUCTION: Cases of lesions that simulate Bowen's disease have been previously
      described in the literature. CASE REPORT: Nine exophytic verruca-like lesions
      with histological findings of Bowen's disease (BD) are described. All cases had a
      rapid growth, and were located on the face and neck of elderly patients with
      chronic solar skin damage. We carried out p16 immunohistochemical staining using
      the immunoperoxidase technique, which was negative in all cases. DISCUSSION: We
      think that these 9 lesions are only histologically mimicking BD, and could be a
      subtype of verruca ('bowenoid wart'). These lesions could be provoked by
      nononcogenic human papillomavirus (HPV), as in other cases previously described.
      The p16 staining was negative in all cases, in contrast with most BD cases. It
      would be interesting to study whether positive p16 staining is related to
      oncogenic HPV, whereas negative p16 staining could be associated with low or
      nononcogenic HPV; thus, more studies are needed.

PMID- 18832811
TI  - Anti-CTLA4 monoclonal antibody induced sarcoidosis in a metastatic melanoma
      patient.

PMID- 18832812
TI  - Facial flush reaction after alcohol ingestion during topical pimecrolimus and
      tacrolimus treatment.

PMID- 18832813
TI  - Thalidomide-related headache.

PMID- 18832814
TI  - Melanoma and immunosuppression.

PMID- 18832815
TI  - Antinuclear antibodies in patients with prurigo pigmentosa: a linkage or a
      coincidence?

PMID- 18832816
TI  - Speech performance and sound localization in a complex noisy environment in
      bilaterally implanted adult patients.
AB  - OBJECTIVE: To evaluate speech performance, in quiet and noise, and localization
      ability in adult patients who had undergone bilateral and simultaneous
      implantation. STUDY DESIGN: Prospective multi-center study. METHODS: Twenty-seven
      adult patients with profound or total hearing loss were bilaterally implanted in
      a single-stage procedure, and simultaneously activated (Med-El, Combi 40/40+).
      Subjects were assessed before implantation and at 3, 6 and 12 months after switch
      on. Speech perception tests in monaural and binaural conditions were performed in
      quiet and in noise using disyllabic words, with speech coming from the front and
      a cocktail party background noise coming from 5 loudspeakers. Sound localization
      measurements were also performed in background noise coming from 5 loudspeakers
      positioned from -90 degrees to +90 degrees azimuth in the horizontal plane, and
      using a speech stimulus. RESULTS: There was a bilateral advantage at 12 months in
      quiet (77 +/- 5.0% in bilateral condition, 67 +/- 5.3% for the better ear, p <
      0.005) and in noise (signal-to-noise ratio +15 dB: 63 +/- 5.9% in bilateral
      condition, 55 +/- 6.9% for the better ear, p < 0.05). Considering unilateral
      speech scores recorded in quiet at 12 months, subjects were categorized as 'good
      performers' (speech comprehension score > or =60% for the better ear, n = 19) and
      'poor performers' (n = 8). Subjects were also categorized as 'asymmetrical'
      (difference between their 2 unilateral speech scores > or =20%, n = 11) or
      'symmetrical' (n = 16). The largest advantage (bilateral compared to the better
      ear) was obtained in poor performers: +19% compared to +7% in good performers (p
      < 0.05). In the group of good performers, there was a bilateral advantage only in
      cases of symmetrical results between the 2 ears (n = 10). In the group of poor
      performers, the bilateral advantage was shown in both patients with symmetrical
      (n = 6) and asymmetrical results (n = 2). In bilateral conditions, the sound
      localization ability in noise was improved compared to monaural conditions in
      patients with symmetrical and asymmetrical performance between the 2 ears. No
      preoperative factor (age, duration of deafness, use of hearing aids, etiology,
      etc.) could predict the asymmetrical performance, nor which ear would be the
      best. CONCLUSION: This study demonstrates a bilateral advantage (at 12 months
      after the implantation) in speech intelligibility and sound localization in a
      complex noisy environment. In quiet, this bilateral advantage is shown in cases
      of poor performance of both ears, and in cases of good performance with
      symmetrical results between the 2 ears. No preoperative factor can predict the
      best candidates for a simultaneous bilateral implantation.

PMID- 18832817
TI  - Effects of human growth hormone on haematopoietic recovery of rats receiving
      chemotherapy.
AB  - Human growth hormone (hGH) is a pleiotropic cytokine targeting a variety of
      tissues. Its protective effects on haematopoiesis during treatment with
      chemotherapeutic drugs were investigated. Sprague-Dawley rats were
      intraperitoneally administered with both carboplatin and 5-fluorouracil together
      with or without recombinant hGH (rhGH) at a dose of 1 IU/kg/day. Body weight,
      full blood count, bone marrow differential count and expression of proliferating
      cell nuclear antigen (PCNA) in bone marrow were measured weekly for 4 weeks in
      chemotherapy-treated (CT) or chemotherapy plus rhGH-treated (CT+GH) animals.
      During the first week, body weight, white blood cell count, haematopoietic count
      and reticulocyte count were decreased in the CT group as well as in the CT+GH
      group, but to a lesser extent in the latter group (CT vs. CT+GH group, p < 0.05).
      Further decreases were also prevented in the CT+GH group. Myeloid cells were
      extremely hypoplastic in the CT group, while in the CT+GH group, myeloid cells
      recovered from obviously hypoplastic to excessively hyperplastic in the first 2
      weeks, and the myeloid karyocyte count increased significantly (CT+GH vs. CT
      group, p < 0.05). PCNA-positive cell count in the CT+GH group was also
      significantly higher than in the CT group (CT+GH vs. CT group, p < 0.05). Thus,
      rhGH showed a promising protective effect on body weight loss and haematopoietic
      recovery of chemotherapy-treated rats, which may be useful in clinic to reduce
      the side effects of chemotherapy.

PMID- 18832818
TI  - 4-Diazopyrazole derivatives as potential new antibiofilm agents.
AB  - BACKGROUND: The recognition that chronic infections and infections associated
      with medical devices are biofilm related has been the impulse for investigating
      the antibiofilm properties of some diazopyrazoles biologically active as
      antimicrobials. METHODS: The susceptibility of staphylococcal biofilms was
      determined at concentrations ranging from 25 to 1.5 microg/ml using crystal
      violet and methylthiazotetrazolium (MTT) staining. In the case of Candida
      albicans, we first assessed the anti-germ tube formation effect of 4-NO2
      (compound 1c) and then we evaluated its antibiofilm activity at concentrations
      ranging from 100 to 6.2 microg/ml. RESULTS: All the compounds were active against
      reference staphylococcal biofilm strains at the maximum tested concentration of
      25 microg/ml; despite its remarkable activity as germ tube inhibitor, compound 1c
      showed weak activity against C. albicans biofilms at 100 microg/ml. CONCLUSION: 4
      Diazopyrazoles represent an interesting source of antimicrobial compounds in the
      development of new antibiofilm agents.

PMID- 18832819
TI  - Antitumor activity of a new N-substituted thiourea derivative, an EGFR signaling
      targeted inhibitor against a panel of human lung cancer cell lines.
AB  - Epidermal growth factor receptor (EGFR) is one of the important protein tyrosine
      kinases (PTKs), whose blockade by tyrosine kinase inhibitors (TKIs) has been
      introduced in the treatment of advanced non-small-cell lung cancers (NSCLCs).
      However, intrinsic and acquired resistance to the clinically used erlotinib or
      gefitinib leads to poor overall prognosis. The novel EGFR-TKI will provide
      alternative choices in NSCLC treatment and might be beneficial. We have
      previously reported the design and synthesis of a novel class of PTK inhibitors
      featuring the N-(2-oxo-1,2-dihydro-quinolin-3-ylmethyl)-thiourea framework. In
      this study, we examined the antitumor effect of compound 5a (DC27) in a panel of
      human lung carcinoma cell lines. The results of a bromodeoxyurdine (BrdU)
      incorporation assay revealed that cell proliferation was inhibited in a dose
      dependent manner, with an IC(50) of 2.5-12.9 microM, similar to gefitinib (1.1
      15.6 microM). DC27 induced G(0)/G(1) arrest of cell cycle and apoptosis as tested
      by flow cytometry. DC27 markedly reduced tyrosine phosphorylation of EGFR and
      inhibited activation of Erk1/2 and AKT, two key downstream effectors of
      proliferation. In conclusion, DC27 has potent in vitro cytotoxicity against human
      lung carcinoma cells, possibly mediated by induction of apoptosis and cell cycle
      arrest in G(0)/G(1) phase.

PMID- 18832820
TI  - Nevirapine toxicity in non-HIV cancer patients.
AB  - BACKGROUND: Nevirapine (NVP) is a nonnucleoside reverse transcriptase inhibitor
      used in HIV patients and recently evaluated as a differentiating and
      antiproliferative agent in human malignancies. However, while NVP is a safe
      treatment in immunocompromised patients, NVP-containing regimens have been
      associated with severe immune-mediated toxicities in non-HIV individuals. METHODS
      AND RESULTS: We describe the toxicity profile of single-agent NVP in 6 non-HIV
      cancer patients treated for a median period of 7.3 months (range 1-24), reporting
      only a reversible grade III increase in glutamyl transpeptidase and glutamic
      pyruvic transaminase serum values. Interestingly, NVP treatment correlates with
      either a decrease in CD8+ T cell counts or a parallel increase in CD4/CD8 ratio,
      antithyroglobulin and antithyroid peroxidase autoantibody titers. CONCLUSIONS:
      These results, although obtained in a small cohort of patients, suggest that the
      toxicity profile of single-agent NVP may be worth testing in a phase I/II study
      in non-HIV cancer patients and that NVP toxicity may depend on its capacity to
      trigger autoimmune responses in susceptible individuals.

PMID- 18832821
TI  - Phase II trial of S-1 in combination with oxaliplatin in previously untreated
      patients with recurrent or inoperable biliary tract cancer.
AB  - BACKGROUND: Biliary tract cancers are among the most aggressive tumors with a
      poor prognosis. We conducted a phase II study on combination chemotherapy
      consisting of S-1 and oxaliplatin in previously untreated patients. METHODS:
      Patients were treated with S-1 40 mg/m(2) twice daily, administered orally on
      days 1-28, and 85 mg/m(2) of oxaliplatin, administered via an intravenous 90-min
      infusion on days 1, 15 and 29. Treatments were repeated every 6 weeks. RESULTS:
      15 patients were enrolled: 9 patients (60%) had intrahepatic and 3 (20%) had
      extrahepatic cholangiocarcinoma, 2 (13.3%) had cancer of the ampulla of Vater and
      1 patient had gall bladder cancer. Partial response was observed in 1 of the 15
      (6.7%) patients. Stable disease was observed in 4 patients (26.7%). The median
      time to progression was 1.4 months (95% confidence interval, CI, 0.9-1.9), and
      the median overall survival was 3.1 months (95% CI, 0.0-7.0). Grade 3 hematologic
      toxicities included neutropenia (1, 6.7%) and thrombocytopenia (1, 6.7%). As the
      response rate in stage I did not justify progression to stage II (> or =2/15),
      this study had to be discontinued in accordance with the established protocols.
      CONCLUSION: The combination chemotherapy with S-1 and oxaliplatin utilized in
      this study resulted in no promising antitumor activity.

PMID- 18832822
TI  - Gefitinib increases serum concentrations of oral irinotecan and SN-38 without
      increasing the biliary concentration of SN-38 in rats.
AB  - BACKGROUND: Gefitinib competes with topoisomerase I inhibitors at drug efflux
      pumps in vitro. We evaluated the effects of oral gefitinib on pharmacokinetic
      parameters of orally coadministered irinotecan. METHODS: We measured the serum
      pharmacokinetic parameters and biliary excretion of irinotecan, SN-38 and its
      glucuronide after irinotecan (50 or 100 mg/kg) was orally administered with or
      without gefitinib 100 mg/kg to rats. We measured the concentrations of irinotecan
      and SN-38 in the small intestine, liver, lungs and kidneys in each rat. RESULTS:
      The plasma area under the curve (0-24 h) of irinotecan and SN-38 was increased
      significantly, while the apparent elimination constant of irinotecan was
      decreased significantly. Gefitinib significantly increased the biliary cumulative
      amounts of irinotecan, but not of SN-38, and also influenced the enterohepatic
      circulation of irinotecan, but not of SN-38. CONCLUSIONS: Gefitinib increased the
      serum concentrations of irinotecan and SN-38 following oral administration of
      irinotecan without increasing the biliary excretion of SN-38 in vivo.

PMID- 18832823
TI  - Antimicrobial susceptibilities of 930 Haemophilus influenzae clinical strains
      isolated from the island of Crete, Greece.
AB  - BACKGROUND: Haemophilus influenzae is an important human pathogen. MATERIALS AND
      METHODS: The purpose of the present retrospective study is to describe the
      antibiotic susceptibility to several common antibiotics of 930 consecutive
      clinical isolates of H. influenzae over the period of 1996-2005 in a tertiary
      general hospital on the island of Crete, Greece. RESULTS: Overall, 9.5% of the
      isolates were beta-lactamase producing. Resistance to ampicillin and amoxicillin
      clavulanate was observed in 11 and 0.6% of the strains, respectively, remaining
      stable throughout the study period. Resistance to tetracycline increased from
      1.6% in 1996 to 38% in 2005, while resistance to ciprofloxacin and ofloxacin was
      <1%. A significant decrease in resistance to trimethoprim-sulfamethoxazole was
      observed during the study period. No significant changes in resistance to other
      antimicrobials were seen. CONCLUSIONS: Amoxicillin-clavulanate and older
      quinolones remain potent agents against H. influenzae. Constant surveillance
      ofantibiotic susceptibility of H. influenzae clinical isolates is important in
      order to guide appropriate empirical antibiotic therapy.

PMID- 18832824
TI  - Prevalence and outcome of congenital left ventricular aneurysms and diverticula
      in an adult population.
AB  - OBJECTIVES: We sought to investigate the prevalence and clinical outcome of
      congenital left ventricular aneurysms (LVAs) and diverticula (LVD) in a large
      adult population. METHODS: We retrospectively studied the left ventricular
      angiograms of 12,271 consecutive patients undergoing cardiac catheterization at
      our institution and analyzed the medical records of the patients. RESULTS: The
      overall prevalence of LVA/LVD was 0.76% (94 patients): there were 42 patients
      with LVA (0.34%) and 52 patients with LVD (0.42%). Men were more likely to have
      LVA (62 vs. 38%), and women were more likely to have LVD (75 vs. 25%; p = 0.001
      for both). The mean time of follow-up was 56 +/- 6 months and was focused on
      clinical events, rehospitalization and survival. Mortality was 6% with no cardiac
      death. Patients with LVD were significantly more likely to have embolic events (p
      = 0.04). Patients with LVA and LVD were more likely to have rhythm disturbances
      compared with controls (p = 0.01 for both). Incidence of syncope was not
      different in both groups (p = 0.4 and 0.12, respectively). There was no reported
      incidence of rupture. CONCLUSION: This large single-center study suggests that
      the prevalence of LVA/LVD in adults is up to 20-fold higher than previously
      reported. One third of the affected patients in our series had nonfatal
      cardiovascular events during follow-up, with a predominance of embolic events in
      the LVD group.

PMID- 18832825
TI  - Atenolol is inferior to metoprolol in improving left ventricular function and
      preventing ventricular remodeling in dogs with heart failure.
AB  - OBJECTIVES: beta-Blockers are standard therapy for patients with heart failure
      (HF). This study compared the effects of chronic monotherapy with 2 different
      beta(1)-selective adrenoceptor blockers, namely atenolol and metoprolol
      succinate, on left ventricular (LV) function and remodeling in dogs with coronary
      microembolization-induced HF [LV ejection fraction (EF) 30-40%]. METHODS: Twenty
      HF dogs were randomized to 3 months of therapy with atenolol (50 mg once daily, n
      = 6), metoprolol succinate (100 mg, once daily, n = 7) or to no therapy (control,
      n = 7). LV EF and volumes were measured before initiating therapy and after 3
      months of therapy. The change (Delta) in EF and volumes between measurements
      before and after therapy was calculated and compared among study groups. RESULTS:
      In controls, EF decreased and end-systolic volume increased. Atenolol prevented
      the decrease in EF and the increase in ESV. In contrast, metoprolol succinate
      significantly increased EF and decreased end-systolic volume. DeltaEF was
      significantly higher and Deltaend-systolic volume significantly lower in
      metoprolol succinate-treated dogs compared to atenolol-treated dogs (EF: 6.0 +/-
      0.86% vs. 0.8 +/- 0.85%, p < 0.05; end-systolic volume: -4.3 +/- 0.81 ml vs. -1
      +/- 0.52 ml, p <0.05). CONCLUSIONS: In HF dogs, chronic therapy with atenolol
      does not elicit the same LV function and remodeling benefits as those achieved
      with metoprolol succinate.

PMID- 18832826
TI  - The renin-angiotensin-aldosterone system: approaches to guide angiotensin
      converting enzyme inhibition in patients with coronary artery disease.
AB  - Drugs that modulate the renin-angiotensin-aldosterone system (RAAS) play an
      important role in modern cardiovascular prevention strategies. Inhibitors of the
      RAAS, in particular angiotensin-converting enzyme (ACE) inhibitors, have been
      proven to be beneficial in specific patient groups, including patients with
      hypertension, heart failure, diabetes mellitus and stable coronary artery
      disease. Although clinical trials demonstrated a rather consistent beneficial
      effect of ACE inhibitors across groups of patients based on clinical
      characteristics, the variability in treatment response on the individual patient
      level is extensive. Recent publications suggest that genetic polymorphisms in the
      RAAS are related to cardiovascular risk. Genetic variability also seems
      associated with the response to ACE inhibitor therapy, and can probably be used
      to tailor treatment. This review discusses several approaches to guide ACE
      inhibitor therapy in patients with coronary artery disease. In addition, the
      potential impact of pharmacogenetics regarding this particular topic is
      highlighted.

PMID- 18832827
TI  - Caries ecology revisited: microbial dynamics and the caries process.
AB  - In this essay we propose an extension of the caries ecological hypothesis to
      explain the relation between dynamic changes in the phenotypic/genotypic
      properties of plaque bacteria and the demineralization/remineralization balance
      of the caries process. Dental plaque represents a microbial ecosystem in which
      non-mutans bacteria (mainly non-mutans streptococci and Actinomyces) are the key
      microorganisms responsible for maintaining dynamic stability on the tooth surface
      (dynamic stability stage). Microbial acid adaptation and subsequent acid
      selection of 'low-pH' non-mutans bacteria play a critical role for destabilizing
      the homeostasis of the plaque by facilitating a shift of the
      demineralization/remineralization balance from 'net mineral gain' to 'net mineral
      loss' (acidogenic stage). Once the acidic environment has been established,
      mutans streptococci and other aciduric bacteria may increase and promote lesion
      development by sustaining an environment characterized by 'net mineral loss'
      (aciduric stage). Hence, high proportions of mutans streptococci and/or other
      aciduric bacteria may be considered biomarkers of sites of particularly rapid
      caries progression. This cascade of events may change the surface texture of
      caries lesions from smooth to rough (enamel) or hard to soft (dentin). These
      clinical surface features can be reversed at any stage of lesion development
      provided that the acidogenic/aciduric properties of the biofilm are resolved.
      From an ecological point of view it is therefore not only important to describe
      which bacteria are involved in caries, but also to know what the bacteria are
      doing.

PMID- 18832828
TI  - Fluoride concentration in dentin of exfoliated primary teeth as a biomarker for
      cumulative fluoride exposure.
AB  - A biomarker for lifetime fluoride exposure would facilitate population-based
      research and policy making but currently does not exist. This study examined the
      suitability of primary tooth dentin as a biomarker by comparing dentin fluoride
      concentration and fluoride exposures. Ninety-nine children's exfoliated primary
      teeth were collected from 2 fluoridated and 2 fluoride-deficient communities in
      North Carolina. Coronal dentin was isolated by microdissection and fluoride
      concentration assayed using the microdiffusion, ion-specific electrode technique.
      Information on children's fluoride exposures since birth from drinking water,
      toothpaste, supplements, rinses, food and beverages was collected by a self
      reported questionnaire administered to caregivers. Only a small portion of the
      variance (10%) in incisor dentin fluoride (mean 792, SD 402 mg/kg) was accounted
      for by the best linear regression model as evaluated by the adjusted R(2). A
      moderate portion of the variance (60%) of molar dentin fluoride (mean 768, SD 489
      mg/kg) was predicted by dietary fluoride supplement exposures, community of
      residence, and frequent tea consumption. Results for molars suggest that primary
      tooth dentin concentration may prove to be a satisfactory biomarker for fluoride
      exposure.

PMID- 18832829
TI  - Effects of different kinds of fluorides on enolase and ATPase activity of a
      fluoride-sensitive and fluoride-resistant Streptococcus mutans strain.
AB  - Enolase and ATPase are sensitive to fluoride. It is unclear whether this
      sensitivity differs for F-sensitive and F-resistant cells or for different types
      of fluoride. Permeabilized cells of the fluoride-sensitive strain Streptococcus
      mutans C180-2 and its fluoride-resistant mutant strain C180-2 FR were
      preincubated at pH 7 or 4 with NaF, the amine fluorides Olaflur and Dectaflur and
      amine chloride controls. After preincubations, enolase and ATPase activities of
      the cells were assessed. Enolase activity was more inhibited after preincubation
      at pH 7 with NaF than with Olaflur. Amine chloride stimulated, although not with
      statistical significance, the enolase activity of both strains. After
      preincubation at pH 4 the enolases were strongly inactivated, but the fluoride
      resistant strain's enolase to a lesser extent. The results suggested that amine
      acts to protect enolase activity against the detrimental low pH effect. Gene
      sequencing showed that the enolase genes of the fluoride-resistant and fluoride
      sensitive strain were identical. ATPase activity was not reduced after NaF
      preincubation at either pH 7 or pH 4. The amine fluorides and their chloride
      controls in the preincubation mixture reduced the ATPase activity significantly
      at both pH values. In conclusion, our results showed that preincubation with
      amine fluoride did not inhibit enolase activity more effectively than NaF. The
      amine part of the molecule may protect enolase activity against preincubations at
      low pH. ATPase activity was not inhibited by NaF preincubation but was
      significantly inhibited after preincubation with amine fluorides and amine
      chlorides.

PMID- 18832830
TI  - Effects of sucrose on the extracellular matrix of plaque-like biofilm formed in
      vivo, studied by proteomic analysis.
AB  - Previous studies have shown that sucrose promotes changes in the composition of
      the extracellular matrix (ECM) of plaque-like biofilm (PLB), but its effect on
      protein expression has not been studied in vivo. Therefore, the protein
      compositions of ECM of PLB formed with and without sucrose exposure were analyzed
      by two-dimensional gel electrophoresis and matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). For this
      purpose, a crossover study was conducted during two phases of 14 days each,
      during which a volunteer wore a palatal appliance containing eight enamel blocks
      for PLB accumulation. In each phase, a 20% sucrose solution or distilled and
      deionized water (control) were extraorally dripped onto the blocks 8x/day. On the
      14th day, the PLB were collected, the ECM proteins were extracted, separated by
      two-dimensional gel electrophoresis, digested by in-gel trypsin and MALDI-TOF MS
      analyzed. In the ECM of PLB formed under sucrose exposure, the following changes
      compared with the control PLB were observed: (1) the presence of upregulated
      proteins that may be involved in bacterial response to environmental changes
      induced by sucrose and (2) the absence of calcium-binding proteins that may
      partly explain the low inorganic concentration found in ECM of PLB formed under
      sucrose exposure. The findings showing that sucrose affected the ECM protein
      composition of PLB in vivo provide further insight into the unique cariogenic
      properties of this dietary carbohydrate.

PMID- 18832831
TI  - Streptococcus mutans and Streptococcus sanguinis colonization correlated with
      caries experience in children.
AB  - The aim of this study was to examine the colonization of Streptococcus mutans and
      Streptococcus sanguinis in the oral cavity and the association with severe early
      childhood caries (S-ECC). Saliva and plaque samples were collected from 14 S-ECC
      children and 8 caries-free (CF) children. All S-ECC children were S. mutans
      positive; 100% of CF children and 93% of S-ECC children were S. sanguinis
      positive. The children's caries severity was positively correlated with levels of
      S. mutans (p < 0.001), total oral streptococci (p < 0.01), total cultivable oral
      bacteria (p < 0.05), and children's age (p < 0.05). Logistic regression analysis
      showed that the interaction of S. sanguinis with S. mutans was a significant
      factor associated with the caries status in children, suggesting that the
      relative levels of these two microorganisms in the oral cavity play an important
      role in caries development.

PMID- 18832832
TI  - Diminished expression of apical sodium-dependent bile acid transporter in
      gallstone disease is independent of ileal inflammation.
AB  - BACKGROUND: Non-obese gallstone patients exhibit a diminished expression of
      apical sodium-dependent bile acid transporter (ASBT) in terminal ileum. Crohn's
      ileitis demonstrates a significant downregulation of this transporter. AIM: To
      test whether subclinical ileal inflammation contributes to gallstone disease.
      METHODS: Biopsies from terminal ileum of female subjects with gallstone disease
      (n = 7), active Crohn's disease (n = 17) and controls (n = 22) were investigated.
      mRNA expression of ASBT, tumor necrosis factor-alpha (TNF-alpha), interleukin
      (IL)-1beta, IL-8, c-jun and c-fos was measured. c-jun and c-fos protein levels
      were determined and hematoxylin and eosin staining was applied for ileal
      histology. RESULTS: ASBT expression was comparably low both in gallstone (47% of
      controls, p = 0.0093) and Crohn's disease (42% of controls, p = 0.0008). In
      gallstone disease there was a non-significant trend towards elevated TNF-alpha
      and IL-1beta, but all cytokines were increased in active Crohn's disease. c-jun
      and c-fos were slightly diminished in patients with gallstones. Neither cytokines
      nor transcription factors correlated significantly with ASBT. The gallstone
      associated ileal biopsies exhibited no histological inflammation. CONCLUSION:
      Although the expression of ASBT was similarly diminished in both gallstone and
      Crohn's disease, subclinical ileal inflammation does not appear to be relevant in
      gallstone patients. The mechanisms of transcriptional repression of ASBT in both
      diseases are apparently different.

PMID- 18832833
TI  - Non-erosive reflux disease--defining the entity and delineating the management.
AB  - In the developed world, most patients with gastroesophageal reflux disease (GERD)
      do not exhibit erosions when examined by standard white light endoscopy. Despite
      the high prevalence of such non-erosive reflux disease (NERD), relatively little
      is known of its underlying pathophysiology, hence there is no clear guide to
      clinical management. To establish areas of agreement or uncertainty in NERD, an
      international meeting was held in Vevey, Switzerland, in late 2007. The goal was
      to document current thinking in the areas of clinical presentation, assessment of
      clinical outcome, pathobiological mechanisms, and define optimal clinical
      strategies to diagnose and manage NERD. After extensive debates, the modified
      Delphi technique was utilized to reach a consensus on 85 specific statements. In
      addition, it was proposed that NERD be defined as 'a subcategory of GERD
      characterised by troublesome reflux-related symptoms in the absence of esophageal
      mucosal erosions/breaks at conventional endoscopy and without recent acid
      suppressive therapy'. Evidence in support of this diagnosis may include
      responsiveness to acid suppression therapy, abnormal reflux monitoring or the
      identification of specific novel endoscopic findings. Defining the current state
      of knowledge in NERD should help improve the elucidation and management of this
      condition in the future.

PMID- 18832834
TI  - Epidemiology of non-erosive reflux disease.
AB  - Non-erosive reflux disease (NERD) is a relatively new entity, the definition of
      which has been evolving and involves the use of symptoms, endoscopy, and
      objective evidence of reflux or reflux-related damage. The closest entity to NERD
      that is examined by available epidemiologic studies is defined by the presence of
      gastroesophageal reflux disease (GERD) symptoms in the absence of esophageal
      erosions or Barrett's esophagus. In this review, I identified two population
      based studies, one non-community study, and several endoscopy-based studies that
      provided information on several aspects of NERD. Most of GERD is NERD (50-85%),
      and therefore one can estimate 11-12% of the general population and considerably
      higher proportions of patients presenting to endoscopy (37-87%) may have NERD.
      Risk factors for NERD including absence of hiatus hernia, low BMI, and presence
      of Helicobacter pylori indicate that it is a 'milder' part of the GERD spectrum.
      Other associations of NERD include younger age, female sex, and psychological
      comorbidities that resemble those of functional gut disorders. The temporal
      trends in NERD are unclear, and are probably increasing because GERD symptom
      prevalence has increased.

PMID- 18832835
TI  - How relevant is symptom evaluation in NERD?
AB  - Most patients presenting with esophageal and extraesophageal symptoms of
      gastroesophageal reflux disease (GERD) have negative endoscopic findings and are
      defined as being affected by non-erosive reflux disease (NERD). A correct
      recognition and analysis of symptoms in these patients is essential for an
      appropriate clinical management, as well as for scientific purposes. Symptoms
      alone do not capture all the clinical implications of NERD, but since their
      frequency and severity are strictly related to their influence on quality of
      life, they provide a sufficiently reliable picture of the disease. Most studies
      were carried out on patients with heartburn and regurgitation, and information
      about other clinical manifestations of NERD is extremely limited. Inclusion
      criteria and primary end-points of clinical trials are ill defined, particularly,
      when extraesophageal manifestations are considered. A new, validated instrument
      is now available to correctly measure all possible complains of GERD patients,
      including general well-being. This scale has been used also to identify the level
      of symptom frequency and severity that can be present in perfectly healthy, self
      considering asymptomatic individuals, thus providing the first objective
      definition of 'complete symptom relief'. Through instruments like this, our
      understanding of NERD and its management will certainly further improve in the
      years to come.

PMID- 18832836
TI  - Is conventional endoscopic identification of non-erosive reflux disease adequate?
AB  - Non-erosive reflux disease is defined as the presence of troublesome reflux
      associated symptoms in the absence of mucosal breaks at endoscopy. Given the fact
      that the majority of patients with reflux symptoms will have a normal endoscopy,
      efforts are underway to determine if new endoscopic techniques can identify
      changes heretofore invisible at the time of standard white light endoscopy.
      However, for any new endoscopic technology to be useful, the grading system it
      uses must be accurate, reproducible, easy to remember and easy to interpret.
      These requirements represent a high bar indeed for any new approach to non
      erosive reflux disease. Current techniques under investigation include high
      resolution endoscopy, magnification endoscopy, chromoendoscopy, narrow-band
      imaging and confocal endomicroscopy. All of these new technologies can identify
      minimal abnormalities heretofore not seen with traditional white light endoscopy.
      All of these new techniques allow for more detailed imaging of the esophagus in
      gastroesophageal reflux disease patients which makes this field ripe for re
      examination. The most exciting findings to date are with narrow-band imaging and
      confocal endomicroscopy. However, studies to date are small and require
      validation in larger numbers of patients by larger number of endoscopists.
      Furthermore, it is essential that we do not repeat the mistakes of the past as
      poor interobserver agreement has already been shown for minimal change
      esophagitis, albeit with more primitive technology.

PMID- 18832837
TI  - Structural abnormalities of endoscopy-negative reflux disease--real or perceived?
AB  - About two thirds of individuals affected by gastroesophageal reflux disease
      suffer from endoscopy-negative esophageal reflux disease. Often, these
      individuals do not receive adequate medication. In contrast, erosive reflux
      disease is much better defined and even subclassified as mucosal breaks of the
      esophageal epithelium. It is known from large trials that gastroesophageal reflux
      disease is probably not a categorical disease without further progression. On the
      other hand, the first structural changes of the esophageal epithelium indicating
      the beginning of reflux disease are unknown. Furthermore, it is not known when
      reflux esophagitis is structurally healed (besides symptom relief). Histological
      markers are based on observations made without clinical correlation. It has
      gradually become clear that there are no specific reflux-induced esophageal
      lesions. All described histological criteria can be also observed in other
      esophageal conditions. Structural abnormalities are believed to be found more
      often close to the lesser gastric curvature or the right esophageal wall.
      Furthermore, it could be shown with a standardized biopsy protocol that a good
      correlation with clinical findings is possible. Conventional histological
      criteria include thickness of basal cell layer, length of papillae and
      inflammatory infiltrates. New criteria include dilation of intercellular spaces
      and changes of protein distribution within intercellular spaces. All changes are
      reversible with PPI therapy. In conclusion, structural abnormalities are not
      specific for gastroesophageal reflux disease or NERD but are reversible with PPI,
      which underlines their relevance.

PMID- 18832838
TI  - Precise role of acid in non-erosive reflux disease.
AB  - The fundamental abnormality in gastroesophageal reflux disease is exposure of the
      esophageal epithelium to acidic gastric contents, resulting in histopathologic
      injury and/or symptoms. With increasing understanding of gastroesophageal reflux
      disease, non-erosive reflux disease (NERD) is found to account for >50% of cases
      involving gastroesophageal reflux. There is a good correlation between esophageal
      acid exposure (EAE) and endoscopic changes. Duration of EAE correlates with
      severity of erosive esophagitis (EE), and the number of prolonged acid reflux
      episodes and esophageal exposure to acid and pepsin is increased in more severe
      reflux. However, there is no convincing evidence to support a significant
      difference in the acid secretory capacity between patients with NERD or EE.
      Although acid reflux gives rise to similar symptoms in both NERD and EE patients,
      the underlying mechanism of acid injury may be different. Dilated intercellular
      spaces may be responsible for the enhanced perception of proximal acid reflux and
      dilated intercellular spaces are a feature of NERD patients, irrespective of EAE,
      and can be considered an objective, structural marker of reflux symptoms. Three
      different mechanisms have been proposed to explain the occurrence of heartburn in
      endoscopy-negative patients: esophageal visceral hypersensitivity, sustained
      esophageal contractions, and abnormal tissue resistance. Impaired esophageal
      mucosal resistance or increased sensitivity, even to small amounts of acid
      reflux, plays a key role in the pathophysiology of NERD. Moreover, hyperalgesia
      may be a predominant mechanism in eliciting symptoms in NERD patients.
      Increasingly seen are patients with a poor response to acid suppression
      treatment. Moreover, even double proton pump inhibitor dosing does not completely
      inhibit gastric acid secretion and relieve all symptoms. Thus, current
      definitions of acid reflux require review to increase the sensitivity to
      determine the frequency and implication of short periods of acidity in the
      esophagus. Analysis such as analysis of the area under the H(+) activity time
      curve is one alternative approach for evaluating acid secretion. The precise role
      of acid in NERD needs further clarification.

PMID- 18832839
TI  - Is there a unifying role for visceral hypersensitivity and irritable bowel
      syndrome in non-erosive reflux disease?
AB  - Non-erosive reflux disease (NERD) is a common condition, characterized by
      symptoms that are attributable to reflux of gastric content into the esophagus in
      the absence of erosive lesions in the distal esophagus. The underlying
      pathophysiology is considered to be multifactorial. This review summarizes the
      current understanding of the role of visceral hypersensitivity in the
      pathogenesis of NERD symptoms and the mechanisms implicated in the pathogenesis
      of esophageal hypersensitivity.

PMID- 18832840
TI  - A critical assessment of the current status of non-erosive reflux disease.
AB  - Non-erosive reflux disease (NERD) has assumed increasing prominence in studies of
      gastroesophageal reflux disease (GERD), but it remains a challenge to define NERD
      precisely and to define its place in the investigation and treatment of GERD.
      Most simply, NERD may be defined as GERD in an individual who has no evidence of
      erosions at endoscopy. Unfortunately, the characteristic symptoms of GERD-
      heartburn and regurgitation--are insufficient to identify all GERD patients and,
      hence, the diagnosis of NERD is hampered by the lack of clear criteria for the
      symptomatic diagnosis of GERD. The diagnosis of NERD is hampered further by
      limited interobserver agreement on the endoscopic diagnosis of erosive
      esophagitis and by the fact that endoscopy is often performed soon after patients
      have discontinued therapy. Improvements in endoscopic technology will increase
      the likelihood of identifying small erosions or other reflux-related lesions;
      however, this will increase the proportion of patients considered to have erosive
      esophagitis without defining precisely what constitutes NERD. It is important to
      recognize that NERD is but one manifestation of GERD and that it, like other
      manifestations of GERD, is associated with a marked diminution in patients'
      quality of life. However, this recognition apart, there seems to be little
      practical benefit or understanding to be gained in clinical practice or clinical
      research from considering NERD as a distinct entity or from studying NERD
      patients in isolation. Advances in understanding the pathogenesis of GERD and its
      symptoms may be better served by categorizing GERD with respect to the spectrum
      of its histologic, functional, endoscopic and symptomatic manifestations rather
      than by studying NERD, a manifestation that is characterized solely by the
      absence of esophageal erosions.

PMID- 18832841
TI  - Non-erosive reflux disease--some clinical case scenarios.
AB  - The consensus meeting attempted to clarify concepts associated with the clinical
      entity often termed 'NERD' and to define it in a way that would permit physicians
      to communicate accurately amongst each other when they use the term, so that
      there may be a common understanding of the condition. In this paper, eight
      clinical case scenarios are presented that illustrate some points of potential
      uncertainty and ambiguity in the use of the term NERD and the clinical management
      of patients. They are discussed in relation to views reached by the consensus
      group.

PMID- 18832842
TI  - Economic reflections on proton pump inhibitor therapy for non-erosive reflux
      disease.
AB  - Proton pump inhibitor (PPI) therapy for gastroesophageal reflux disease is a good
      example of the evolution of economic analysis. Initial studies were simple models
      constructed on spreadsheets and described the most cost-effective therapy in
      terms of cost per cure of esophagitis. This tells a third-party payer what is the
      most efficient approach to healing esophagitis (technical efficiency) but does
      not give any indication of whether treating esophagitis is good value for money
      in the first place or whether health care dollars would be better spent in
      treating other diseases (allocative efficiency). As economic analyses became more
      sophisticated, more complex models were constructed. Outcomes were expressed in
      terms of cost per quality-adjusted life year gained or the question was framed in
      terms of the probability a strategy would be cost effective depending on
      willingness to pay for a month free from symptoms. These approaches answer the
      question of whether treating gastroesophageal reflux disease is good value for
      money. Models have traditionally evaluated treatment of esophagitis, but this
      does not address the most efficient therapy of non-erosive reflux disease. This
      article describes a simplified model (for illustrative purposes only) and
      suggests that PPI therapy is a cost-effective approach for the treatment of
      esophagitis whether generic or proprietary PPI costs are applied. PPI therapy is
      also likely to be a cost-effective strategy for non-erosive reflux disease at
      generic but not at proprietary prices.

PMID- 18832843
TI  - Local versus general anaesthesia with Prolene Hernia System mesh for inguinal
      hernia repair: early and long-term outcomes.
AB  - BACKGROUND: There are minimal data regarding the feasibility of Prolene Hernia
      System repair under local anaesthesia and patient acceptability. This study
      analyses the outcomes of Prolene Hernia System repair under different anaesthetic
      techniques. METHODS: A retrospective review of all Prolene Hernia System repairs
      over a 5-year period was performed. The outcome measures were type of anaesthesia
      used, early and late complications, recurrence and patient satisfaction. RESULTS:
      100 repairs were analysed. Seventy repairs were performed under local anaesthesia
      and 30 under general anaesthesia. The number of patients with a body mass index
      >30 were 17 (24%) and 8 (27%), respectively, in the local- and general
      anaesthesia groups (p = 0.7). Day cases were higher in the local-anaesthesia
      group (69 days vs. 16 days, p = 0.001). Early complications were similar in the
      two groups. 18 (26%) patients in the local-anaesthesia group and 6 (19%) in the
      general-anaesthesia group developed chronic groin pain (p = 0.6). One recurrence
      was noted in the local-anaesthesia group. Patient satisfaction was high with both
      anaesthetic techniques. CONCLUSIONS: Prolene Hernia System repair under local
      anaesthesia results in increased day cases with similar complication rates
      compared to general anaesthesia. Both anaesthetic techniques are associated with
      good outcomes and excellent patient satisfaction.

PMID- 18832844
TI  - A novel mutation in the arylsulfatase A gene associated with adult-onset
      metachromatic leukodystrophy without clinical evidence of neuropathy.

PMID- 18832845
TI  - Palatal Myoclonus (syn. Palatal Tremor).
AB  - Symptomatic palatal tremor is caused by a lesion in the triangle of Guillain and
      Mollaret and is associated with hypertrophic olivary degeneration that has
      multiple causes. Essential palatal tremor has no currently demonstrable cause and
      no accompanying physical or radiological signs. But it is probable that an
      organic genesis will become apparent. I suggest that some examples of palatal
      tremor may depend on an 'upper motor neurone type', i.e. supranuclear, lesion in
      the striatum or rostral brainstem releasing medullary activation with denervation
      hypersensitivity of olivary neurones.

PMID- 18832846
TI  - Mollaret's meningitis.
AB  - Pierre Mollaret is mainly known for his contributions to infectious diseases and
      their prevention. He also described benign, recurrent endothelio-leukocytic
      meningitis in three patients who had short-lived recurrent attacks of fever,
      headache and vomiting caused by sterile meningitis, with 'fantomes cellulaires'
      (cell ghosts) in the cerebrospinal fluid. Identical symptoms are caused by Herpes
      simplex virus-2 and other viruses. The term Mollaret's meningitis should be
      restricted to idiopathic recurrent aseptic meningitis. This paper briefly
      outlines the syndrome and its discoverer.

PMID- 18832847
TI  - Radical/radiculopathy.

PMID- 18832848
TI  - Gender-specific weight estimation of fetuses between 2,501 and 3,999 g--new
      regression formulae.
AB  - OBJECTIVE: To develop new gender-specific regression formulae to estimate fetal
      weight focusing on a particular weight range from 2,501 to 3,999 g. METHODS:
      3,254 singleton pregnancies were included to generate new regression formulae for
      female and male fetuses, and to evaluate their accuracy. RESULTS: In comparison
      with commonly used formulae, the new gender-specific and weight-range-specific
      method of fetal weight estimation provided greater accuracy. The mean absolute
      error was less than 7%. CONCLUSIONS: When properly used, the new formulae can
      improve the accuracy of weight estimations in fetuses between 2,501 and 3,999 g.

PMID- 18832849
TI  - Hydrops fetalis, thickened placenta and other sonographic findings in a low-level
      trisomy 21 mosaicism: a case report.
AB  - We report a case of trisomy 21 mosaicism detected upon amniocentesis in a 36-year
      old woman. Ultrasound examination at 23 weeks' gestation showed a fetus with
      hydrops, pulmonary hypoplasia, oligohydramnios, thickened placenta, and
      intrauterine growth retardation. Cytogenetic analysis revealed low-percentage
      (6%) mosaicism for trisomy 21. Hydrops fetalis and thickened placenta are
      uncommon findings in fetuses affected by trisomy 21 mosaicism. A short review of
      the literature is given regarding the sonographic findings associated with
      trisomy 21 mosaicism, and the genetic counseling in such cases.

PMID- 18832850
TI  - Prenatal diagnosis of an epignathus associated with a 49,XXXXY karyotype--a case
      report.
AB  - BACKGROUND: Epignathus is a rare form of congenital teratoma, originating from
      the base of the skull, most commonly the hard palate, or mandible. It has been
      associated with a poor prognosis due to complications including polyhydramnios
      and respiratory compromise at birth as a consequence of upper airway
      obstructions. It is usually not associated with chromosomal aberrations. We
      present a case of prenatally diagnosed epignathus associated with a gonosomal
      pentasomy 49,XXXXY. CASE: A 34-year-old gravida 1, para 0 was referred to our
      unit with a sonographically suspected gastroschisis at 26+6 weeks' gestation. A
      detailed ultrasound scan revealed a large mixed echogenic mass seen in
      continuation with the mouth in the midline. Based on the appearance, an
      epignathus was suspected. No other fetal anomalies were detected. Karyotyping
      showed a 49,XXXXY karyotype of the fetus. The couple decided to continue the
      pregnancy after detailed counseling about results and prognosis. A cesarean
      section was necessary and performed at 29+0 weeks' gestation due to a
      pathological Doppler and cardiotocogram. Because of the enormous epignathus
      intubation of the newborn was not possible. A tracheostomy was performed for
      ventilation and oxygenation, which failed and the newborn died 30 min after
      birth. CONCLUSION: Prenatal diagnosis by ultrasound has improved perinatal
      management. This should include assessment of the tumor size and spread in order
      to establish an accurate prognosis and to anticipate likely problems which are to
      be encountered during pregnancy or at the time of delivery. To our knowledge,
      this is the first reported case of a prenatally diagnosed epignathus with a
      gonosomal pentasomy 49,XXXXY.

PMID- 18832851
TI  - Current status and prospects of fetoscopic surgery for spina bifida in human
      fetuses. Response to Fichter et al: Fetal spina bifida repair--current trends and
      prospects of intrauterine neurosurgery (Fetal Diagn Ther 2008;23:271-286).

PMID- 18832852
TI  - Single large inguinal lymph node metastasis in human papillomavirus-induced early
      invasive vulvar cancer of the anterior fourchette in two young women.
AB  - The incidence of human papillomavirus (HPV)-induced vulvar cancer in young women
      is increasing and often presents as microinvasive or early invasive tumors in a
      grade 3 vulvar intraepithelial neoplasia. So far, the risk of lymph node
      metastases in early invasive vulvar carcinoma (depth of invasion 1.1-2.0 mm) is
      reported to be less than 8%. We present 2 cases of young women with early
      invasive vulvar cancers (depth of invasion 1.5 and 2.0 mm) induced by HPV 16 and
      42. In both cases, the cancers are located between the clitoris and urethra and
      are each accompanied by one groin macro-metastatic lymph node. This case report
      highlights the necessity for complete inguinofemoral lymphadenectomy and/or
      adequate radiation therapy of the groin in early invasive tumors in young women
      to prevent cancer recurrence in the groin. Additionally, the indication for a
      sentinel node procedure in these specific cases requires particular caution.

PMID- 18832853
TI  - Ola Didrik Saugstad--an oxygen radical.

PMID- 18832854
TI  - Injury and inflammation from resuscitation of the preterm infant.
AB  - We review information about how the preterm lung can be injured with the
      initiation of mechanical ventilation at birth. Although multiple variables such
      as pressure, tidal volume, positive end expiratory pressure, and the gas used for
      ventilation may contribute to the injury, the relative contribution of each is
      not known. Recent studies demonstrate that injury caused by initial high tidal
      volume is amplified by subsequent mechanical ventilation. A model for gas
      inflation of the fluid-filled lung may explain why even low tidal volumes may
      injure the preterm lung, and why the injury may initially occur to the small
      airways. Ventilation strategies that minimize injury need to be developed.

PMID- 18832855
TI  - Weaning preterm infants from mechanical ventilation.
AB  - Mechanical ventilatory support is required by a large number of neonates in
      respiratory failure. However, its use in preterm infants is frequently associated
      with acute complications and long-term respiratory sequelae. Therefore, it is
      recommended to avoid or limit the exposure to ventilatory support. This is a
      review of existing practices and novel strategies to achieve weaning of
      ventilatory support in this population.

PMID- 18832856
TI  - Long-term pharmacologic neuroprotection after birth asphyxia: where do we stand?
AB  - Perinatal hypoxia-ischemia or birth asphyxia is a serious complication with a
      high mortality and morbidity. For decades, neuroprotective options have been
      explored to reduce reperfusion and reoxygenation injury to the brain, which
      accounts for a substantial part of birth asphyxia-related brain damage. In this
      review, we focus on neuroprotective strategies with a long-term follow-up,
      reported in both experimental and clinical studies. Strategies related to
      modification of excitatory neurotransmitter production and action, reduction in
      free radical production and inflammation and neoneurogenesis will be briefly
      summarized. Since hypothermia has been proven to be beneficial for a selected
      group of asphyxiated neonates, we assume that a combination of this treatment
      option with a pharmacological means of neuroprotection will be the appropriate
      approach in the future. Finally, it is important to consider possible gender
      effects in view of the discussed pharmacological strategies.

PMID- 18832857
TI  - Early aggressive nutrition for the premature infant.
AB  - Nutrition for sick newborn infants, both term and preterm, has been evolving
      since the first published report of use of total parenteral nutrition (TPN) in an
      infant. The more preterm infants have posed an even greater challenge, because
      optimal timing for use of enteral nutrition is an additional factor for
      completing their nutritional demands. Although benefiting the immune system among
      other physiological benefits, human milk has many nutritional gaps for the
      premature infant. The development of premature infant formulas and milk
      fortifiers has helped fill these gaps, but questions still exist about safety and
      efficacy of human milk versus formula. This article will focus on the use of TPN
      as well as early initiation of enteral feedings and the challenges this brings.

PMID- 18832858
TI  - Choosing a right surfactant for respiratory distress syndrome treatment.
AB  - Respiratory distress syndrome (RDS) is the most common cause of respiratory
      insufficiency in preterm infants, especially those born at <30 weeks of
      gestation. Continuous positive airway pressure has been used since the 1970s as a
      primary mode of treatment for RDS. Surfactant therapy became available in the
      1980s and has become the standard care for infants with or at risk for RDS.
      Surfactant therapy has been shown to decrease air leaks, neonatal and infant
      mortality as well as cost among survivors. Natural surfactants derived from
      animal sources containing surfactant proteins B (SP-B) and C (SP-C) as well as
      synthetic surfactants with functional SP-B- or SP-C-like protein mimics have been
      extensively evaluated in preterm neonates with or at risk for RDS. Evidence from
      randomized controlled trials indicates that treatment with natural surfactants
      results in faster weaning of supplemental oxygen and mean airway pressure,
      decreased duration of mechanical ventilation, and decreased mortality when
      compared to synthetic surfactants. Furthermore, at the present time, there are no
      approved synthetic surfactants available for use in preterm infants. Beractant,
      calfactant and poractant alpha are the three commonly used natural surfactants
      worldwide. Comparative studies including prospective randomized trials as well as
      large retrospective studies have shown significant differences in outcome and
      cost among these three natural surfactants. Of the eight prospective, randomized
      controlled trials and two retrospective studies involving the natural surfactant
      preparations, treatment with poractant alpha resulted in a significantly
      decreased mortality, decreased need for additional doses, faster weaning of
      oxygen and reduced hospital costs when compared to treatment with beractant or
      calfactant. These differences in outcome may be due to differences in
      phospholipid and SP-B content, amount of antioxidant phospholipids, plasmalogens,
      anti-inflammatory properties and viscosity among these three surfactants.
      Additional studies of administering surfactant non-invasively via laryngeal mask
      airway in preterm infants weighing >1,200 g and as an aerosol preparation are
      currently in progress.

PMID- 18832859
TI  - Outcomes of multiplets.
AB  - Outcomes, both short and long term, differ between singletons and multiplets.
      Recently, a number of large, well-designed studies have clarified these
      differences, particularly in light of major changes in perinatal and neonatal
      care that have influenced changing outcomes. Accordingly, this article will
      review risks for singletons, twins and higher-order multiples as whole groups and
      also after correction for gestational age and other potential confounding
      variables that differ markedly between the groups. In addition, we will focus on
      the effects of certain factors such as antenatal steroid therapy and gender.
      Finally, we will detail the specific long-term risks for multiples in terms of
      growth and neurodevelopmental disabilities.

PMID- 18832860
TI  - Differential frontal activation during exogenous and endogenous orientation of
      visuospatial attention. A near-infrared spectroscopy study.
AB  - AIMS: The aim was to measure the prefrontal cortical activity involved in
      shifting spatial attention to visual stimuli in the left or right visual field
      using near-infrared spectroscopy. METHODS: Eleven participants performed a simple
      vigilance task, an endogenous attention task and an exogenous attention task. In
      the endogenous task, the left or the right side of the center diamond brightened,
      indicating the side for subsequent target appearance (controlled shift of
      attention). In the exogenous task, the peripheral squares brightened, indicating
      the appearance of target in those squares (reflexive shift of attention).
      RESULTS: Stimuli at validly cued locations were responded to faster than stimuli
      at invalidly cued locations. Increases in oxyhemoglobin (oxy-Hb) were observed in
      the right prefrontal cortex throughout the 3 tasks, and in the left prefrontal
      cortex during the vigilance and the exogenous tasks. In the exogenous task,
      marked decreases in oxy-Hb were observed in the bilateral ventrolateral
      prefrontal cortex. CONCLUSIONS: These results suggest that the left and the right
      prefrontal cortices mediate distinct cognitive processes during the performance
      of visuospatial attentional tasks.

PMID- 18832861
TI  - Association of A/G polymorphism in intron 13 of the monoamine oxidase B gene with
      schizophrenia in a Spanish population.
AB  - BACKGROUND: Monoamine oxidase B (MAO-B) enzyme is involved in the oxidative
      metabolism of dopamine. We studied whether the A644G polymorphism in intron 13 of
      the MAO-B gene is a risk factor for schizophrenia. METHODS: 242 subjects
      diagnosed with schizophrenia and related disorders and 290 hospital-based
      controls participated in the study. Genomic DNA was isolated from whole blood and
      genotyped with the allele-specific oligonucleotide polymerase chain reaction
      method. RESULTS: This polymorphism was studied by diagnosis subgroups and the G
      allele was identified as a risk factor for developing schizophrenia (p = 0.006).
      When we performed a sex-specific analysis, the G allele was only a risk factor
      for developing schizophrenia in women (p = 0.01). Although the frequency of the G
      allele is higher in male patients than in male controls, no statistically
      significant association with schizophrenia was found. CONCLUSION: Our results
      support the involvement of the MAO-B gene in schizophrenia, particularly in
      women.

PMID- 18832862
TI  - Cytokine Genes TNF, IL1A, IL1B, IL6, IL1RN and IL10, and childhood-onset mood
      disorders.
AB  - BACKGROUND/AIMS: Inflammatory cytokines induce a behavioral syndrome, known as
      sickness behavior, that strongly resembles symptoms typically seen in depression.
      This resemblance has led to the theory that an imbalance of inflammatory cytokine
      activity may be a contributing factor in depressive disorders. Support for this
      is found in multiple lines of evidence, such as the effects of cytokines on the
      activities of the hypothalamic-pituitary-adrenal axis, serotonin and brain
      derived neurotrophic factor, and hippocampal function, all of which are
      implicated in the etiology of depression. In addition, associations between
      inflammatory activity and depressive symptomology have been documented in a
      number of studies, and the depressogenic effects of cytokine therapy are well
      known. Accordingly, given that depression has a substantial genetic basis, genes
      involved in the regulation of inflammatory cytokine activity are strong
      candidates for involvement in genetic susceptibility to depressive disorders.
      Here, we have tested 6 key genes of this type, TNF, IL1A, IL1B, IL6, IL1RN and
      IL10, as candidates for involvement in childhood-onset mood disorders. METHODS:
      In this study of 384 families, each ascertained through a child with depression
      diagnosed before the age of 15 years, 11 polymorphisms of known or likely
      functional significance (coding and regulatory variants) were analyzed. RESULTS:
      Testing for biased transmission of alleles from parents to their affected
      offspring, we found no evidence for an association between childhood-onset mood
      disorders and any of the polymorphisms, either individually or as haplotypes.
      CONCLUSION: The present study does not support the involvement of the TNF, IL1A,
      IL1B, IL6, IL1RN and IL10 variants as major genetic risk factors contributing to
      early-onset mood disorders.

PMID- 18832863
TI  - Disposition of naltrexone after intravenous bolus administration in Wistar rats,
      low-alcohol-drinking rats and high-alcohol-drinking rats.
AB  - Reports have shown that interspecies differences in the metabolism and
      pharmacokinetics of naltrexone are a rule rather than exception. However, there
      is paucity of information on the disposition of naltrexone in selectively bred
      rat lines that reliably exhibit high and low voluntary alcohol consumption, and
      are often used to study alcohol-drinking behavior. We have characterized the
      pharmacokinetic profiles of naltrexone in selectively bred rat lines: high
      alcohol-drinking (HAD-1) and low-alcohol-drinking (LAD-1) rats as well as the
      native Wistar strain. This study was carried out to establish a baseline
      pharmacokinetic profile of naltrexone in these rats prior to evaluating its
      pharmacokinetic profile in polymeric controlled-release formulations in our
      laboratory. The hypothesis is that alcohol-preferring and non-alcohol-preferring
      lines of rats should differ in the disposition of intravenously administered
      naltrexone. Naltrexone administration and blood collection were via the jugular
      vein. In a parallel experiment, naltrexone was administered via the jugular vein,
      but urine was collected using the Nalgene metabolic cage system. Data were
      analyzed by a noncompartmental approach. Results show a high clearance that is
      close to or higher than hepatic blood flow in all groups (Wistar > LAD-1 > HAD-1,
      but with a statistically significant difference only between Wistar and HAD-1).
      Volume of distribution (approximately 2.5-3 l/kg) and the half-life
      (approximately 1 h) were similar. Urinary elimination of naltrexone was small,
      but also showed differences between the rats: HAD-1 > LAD-1 > Wistar, but with a
      statistically significant difference only between HAD-1 and Wistar rats. This
      study has therefore established the baseline disposition characteristics of
      naltrexone in these strains of rats.

PMID- 18832864
TI  - Outreach work by Pancreatology: serving the IAP to support the birth of forward
      looking IAP-sponsored societies.

PMID- 18832865
TI  - Effect of penetration modifiers on the dermal and transdermal delivery of drugs
      and cosmetic active ingredients.
AB  - In this study the effect of 2 penetration modifiers, dimethyl isosorbide (DMI)
      and diethylene glycol monoethyl ether (DGME) on the skin delivery of hydroquinone
      (HQ), salicylic acid (SA) and octadecenedioic acid (DIOIC) was investigated. Ten
      percent DMI and DGME were separately formulated into oil-in-water emulsions
      containing 1.8% HQ, SA and DIOIC, respectively. Skin delivery and the flux across
      split-thickness human skin of the active ingredients were determined using Franz
      diffusion cells. An emulsion with 10% water incorporated instead of the water
      soluble penetration modifiers served as a control. The study showed that neither
      10% DMI nor 10% DGME significantly enhanced the skin permeation of the various
      lipophilic active ingredients or the uptake into the skin. It was hypothesized
      that the addition of the penetration modifiers to the emulsions not only enhanced
      the solubility of the various active ingredients in the skin but also in the
      formulation, resulting in a reduced thermodynamic activity and hence a weaker
      driving force for penetration. Therefore, the effect of DMI and DGME on the
      solubility of the active ingredients in the skin was counteracted by a
      simultaneous reduction in the thermodynamic activity in the formulation.

PMID- 18832866
TI  - Protection against dryness of facial skin: a rational approach.
AB  - Facial skin is unique in that it gets far more exposure to the external
      environment than skin on other areas of the body and paradoxically, because it
      contains the thinnest epidermis and stratum corneum, especially on the eye lid.
      Environmental attacks contribute to drying of facial skin and damage to the
      stratum corneum. In recent years, there has been an explosion of new products
      that contain ingredients that claim to benefit facial skin and protect against
      environmental damage. This review critically examines the scientific basis,
      rationale and evidence for inclusion of these ingredients in products for
      protection of facial skin.

PMID- 18832867
TI  - Seasonal effects on the nasolabial skin condition.
AB  - In the present work, nasolabial skin condition and the influence of seasonal
      changes during autumn and winter were studied in 16 healthy female volunteers.
      Apart from visual scoring of erythema and skin scaliness, transepidermal water
      loss (TEWL), skin hydration, apparent skin pH, skin colour and skin desquamation
      were biophysically measured. The study results showed that nasolabial TEWL was
      significantly higher during wintertime than in autumn. Also skin colour
      measurements and squamometry scorings revealed higher values, indicating a more
      reddish and scaly nasolabial skin during winter compared to autumn. Results from
      tape stripping and skin surface lipid analysis by high-performance thin-layer
      chromatography demonstrated significant differences for triglycerides and
      cholesterol esters, indicating a functionally inferior hydrolipidic layer during
      the winter season.

PMID- 18832868
TI  - Despair and hope in rural South Africa: the story of the antiretroviral drugs
      that are changing lives.

PMID- 18832869
TI  - A call for randomized controlled trials of antiretroviral therapy for HIV-2
      infection in West Africa.

PMID- 18832871
TI  - Antibodies purified from sera of HIV-1-infected patients by affinity on the
      heptad repeat region 1/heptad repeat region 2 complex of gp41 neutralize HIV-1
      primary isolates.
AB  - OBJECTIVE: The objective of this paper was to evaluate the presence and the
      neutralizing activity of antibodies directed against the complex formed between
      the two heptad repeat regions (HR1 and HR2) of HIV-1 gp41 in sera of HIV-1
      infected patients. RESEARCH DESIGNS AND METHODS: The HR1 region was represented
      by the peptide N36 and the maltose-binding protein (MBP)-HR1, the HR2 region by
      the peptide C34 and MBP44. Antibodies directed to the HR1/HR2 complex were
      purified from sera by affinity chromatography using MBP-HR1/C34 adsorbed onto a
      resin. RESULTS: First, we demonstrated that human monoclonal antibodies, which
      are directed specifically to the HR1/HR2 complex recognized in enzyme-linked
      immunosorbent assay the MBP-HR1/C34 and MBP44/N36 mixtures but not the proteins
      or the peptides individually. We investigated the ability of 50 sera of HIV-1
      infected patients to react with the MBP-HR1/C34 and MBP44/N36 complexes. We found
      that the majority of sera of HIV-1-infected patients recognized the HR1/HR2
      complexes but not or to a lower extent the proteins or the peptides individually.
      Antibodies purified from sera by affinity chromatography using MBP-HR1/C34
      adsorbed to a resin neutralized different primary HIV-1 isolates. CONCLUSION: The
      presence of antibodies directed to the HR1/HR2 complex in sera of HIV-infected
      patients highlights the immunogenic character of the complex, whereas the
      neutralizing activity of these antibodies suggests that immunogens representing
      HIV-1 HR1/HR2 complexes might be used in anti-HIV vaccine.

PMID- 18832872
TI  - Restoration of Toxoplasma gondii-specific immune responses in patients with AIDS
      starting HAART.
AB  - OBJECTIVE: To study the kinetics and identify factors associated with Toxoplasma
      specific immune responses in patients with AIDS starting antiretroviral therapy.
      METHODS: A prospective study of 38 HIV-infected patients seropositive for
      Toxoplasma who started antiretroviral therapy with CD4 T cells less than 200
      cells/microl. T-cell and B-cell phenotypes, anti-Toxoplasma antibodies titers, Th
      1 and Th-2 cytokine production and lymphocyte proliferative responses (LPRs) to
      Toxoplasma were assessed over 12 months. RESULTS: Median CD4 cell count increased
      from 122 cells/microl at baseline to 260 cells/microl at 12 months, and the
      incidence of a positive LPR from 18.4 to 70.5%. A Toxoplasma IgG titer more than
      150 IU/ml was the only baseline variable associated with a positive LPR (hazard
      ratio: 4.6, P = 0.003). Among time-dependent covariates, the number of effector
      memory (CD45RA-CCR7-) CD4 T cells was associated with a positive LPR (P < 0.02)
      and the number of terminally differentiated (CD45RA+CCR7-) CD8 T cells was
      associated with in-vitro production of gamma-IFN (P < 0.008). CONCLUSION: Among
      patients with low CD4 cell counts, high anti-Toxoplasma IgG titers were
      associated with LPR to Toxoplasma antigen. After starting antiretroviral therapy,
      the number of effector memory CD4 T cells and terminally differentiated CD8 T
      cells were associated with the restoration of Toxoplasma LPR and gamma-IFN
      production, respectively.

PMID- 18832873
TI  - Long-term consequences of the delay between virologic failure of highly active
      antiretroviral therapy and regimen modification.
AB  - OBJECTIVES: Current treatment guidelines recommend immediate modification of
      antiretroviral therapy in HIV-infected individuals with incomplete viral
      suppression. These recommendations have not been tested in observational studies
      or large randomized trials. We evaluated the consequences of delayed modification
      following virologic failure. DESIGN/METHODS: We used prospective data from two
      clinical cohorts to estimate the effect of time until regimen modification
      following first regimen failure on all-cause mortality. The impact of regimen
      type was also assessed. As the effect of delayed switching can be confounded if
      patients with a poor prognosis modify therapy earlier than those with a good
      prognosis, we used a statistical methodology - marginal structural models - to
      control for time-dependent confounding. RESULTS: A total of 982 patients
      contributed 3414 person-years of follow-up following first regimen failure. Delay
      until treatment modification was associated with an elevated hazard of all-cause
      mortality among patients failing a reverse transcriptase inhibitor-based regimen
      (hazard ratio per additional 3 months delay = 1.23, 95% confidence interval:
      1.08, 1.40), but appeared to have a small protective effect among patients
      failing a protease inhibitor-based regimen (hazard ratio per additional 3 months
      delay = 0.93, 95% confidence interval: 0.87, 0.99). CONCLUSION: Delay in
      modification after failure of regimens that do not contain a protease inhibitor
      is associated with increased mortality. Protease inhibitor-based regimens are
      less dependent on early versus delayed switching strategies. Efforts should be
      made to minimize delay until treatment modification in resource-poor regions,
      where the majority of patients are starting reverse transcriptase inhibitor-based
      regimens and HIV RNA monitoring may not be available.

PMID- 18832874
TI  - Bayesian network analyses of resistance pathways against efavirenz and
      nevirapine.
AB  - OBJECTIVE: To clarify the role of novel mutations selected by treatment with
      efavirenz or nevirapine, and investigate the influence of HIV-1 subtype on
      nonnucleoside reverse transcriptase inhibitor (nNRTI) resistance pathways.
      DESIGN: By finding direct dependencies between treatment-selected mutations, the
      involvement of these mutations as minor or major resistance mutations against
      efavirenz, nevirapine, or coadministrated nucleoside analogue reverse
      transcriptase inhibitors (NRTIs) is hypothesized. In addition, direct
      dependencies were investigated between treatment-selected mutations and
      polymorphisms, some of which are linked with subtype, and between NRTI and nNRTI
      resistance pathways. METHODS: Sequences from a large collaborative database of
      various subtypes were jointly analyzed to detect mutations selected by treatment.
      Using Bayesian network learning, direct dependencies were investigated between
      treatment-selected mutations, NRTI and nNRTI treatment history, and known NRTI
      resistance mutations. RESULTS: Several novel minor resistance mutations were
      found: 28K and 196R (for resistance against efavirenz), 101H and 138Q
      (nevirapine), and 31L (lamivudine). Robust interactions between NRTI mutations
      (65R, 74V, 75I/M, and 184V) and nNRTI resistance mutations (100I, 181C, 190E and
      230L) may affect resistance development to particular treatment combinations. For
      example, an interaction between 65R and 181C predicts that the nevirapine and
      tenofovir and lamivudine/emtricitabine combination should be more prone to
      failure than efavirenz and tenofovir and lamivudine/emtricitabine. CONCLUSION:
      Bayesian networks were helpful in untangling the selection of mutations by NRTI
      versus nNRTI treatment, and in discovering interactions between resistance
      mutations within and between these two classes of inhibitors.

PMID- 18832875
TI  - Efavirenz versus nevirapine-based initial treatment of HIV infection: clinical
      and virological outcomes in Southern African adults.
AB  - OBJECTIVE: To determine the effectiveness of efavirenz versus nevirapine in
      initial antiretroviral therapy regimens for adults in sub-Saharan Africa. DESIGN:
      Observational cohort study. METHODS: Study participants were 2817 HIV-infected,
      highly active antiretroviral therapy-naive adults who began nevirapine-based or
      efavirenz-based highly active antiretroviral therapy between January 1998 and
      September 2004 via a private-sector HIV/AIDS program in nine countries of
      southern Africa. The primary outcome was time to virologic failure (two
      measurements of viral loads >or=400 copies/ml). Secondary outcomes included all
      cause mortality, time to viral load less than 400 copies/ml, pharmacy-claim
      adherence, and discontinuation of nevirapine or efavirenz without virologic
      failure. RESULTS: The median follow-up period was 2.0 years (interquartile range
      1.2-2.6). Patients started on nevirapine were significantly less likely than
      those started on efavirenz to achieve high adherence, whether defined as 100%
      (30.2 versus 38.1%, P < 0.002) or more than 90% (44.8 versus 49.4%, P < 0.02)
      pharmacy-claim adherence. In a multivariate analysis, patients on nevirapine had
      greater risk of virologic failure [hazard ratio (HR 1.52; 95% confidence interval
      (CI) 1.24-1.86)], death (2.17; 1.31-3.60), and regimen discontinuation (1.67;
      1.32-2.11). Switching from nevirapine to efavirenz had no significant virologic
      effect, whereas switching from efavirenz to nevirapine resulted in significantly
      slower time to suppression (hazard ratio 0.58, 95% confidence interval 0.35-0.93)
      and faster time to failure (hazard ratio 3.92; 95% confidence interval 1.61-9.55)
      than remaining on efavirenz. CONCLUSION: In initial highly active antiretroviral
      therapy regimens, efavirenz was associated with superior virologic and clinical
      outcomes than nevirapine, suggesting that efavirenz might be the preferred
      nonnucleoside reverse transcriptase inhibitor in resource-limited settings.
      However, its higher cost and potential teratogenicity are important barriers to
      implementation.

PMID- 18832876
TI  - National estimation of rates of HIV serology testing in US emergency departments
      1993-2005: baseline prior to the 2006 Centers for Disease Control and Prevention
      recommendations.
AB  - OBJECTIVE: The 2006 Centers for Disease Control and Prevention recommendations
      place increased emphasis on emergency departments (EDs) as one of the most
      important medical care settings for implementing routine HIV testing. No
      longitudinal estimates exist regarding national rates of HIV testing in EDs. We
      analyzed a nationally representative ED database to assess HIV testing rates and
      characterize patients who received HIV testing, prior to the release of the 2006
      guidelines. DESIGN: A cross-sectional analysis of US ED visits (1993-2005) using
      the National Hospital Ambulatory Medical Care Survey was performed. METHODS:
      Patients aged 13-64 years were included for analysis. Diagnoses were grouped with
      Healthcare Cost and Utilization Project Clinical Classifications Software.
      Analyses were performed using procedures for multiple-stage survey data. RESULTS:
      HIV testing was performed in an estimated 2.8 million ED visits (95% confidence
      interval, 2.4-3.2) or a rate of 3.2 per 1000 ED visits (95% confidence interval,
      2.8-3.7). Patients aged 20-39 years, African-American, and Hispanic had the
      highest testing rates. Among those tested, leading reasons for visit were
      abdominal pain (9%), puncture wound/needlestick (8%), rape victim (6%), and fever
      (5%). The leading medication class prescribed was antimicrobials (32%). The
      leading ED diagnosis was injury/poisoning (30%) followed by infectious diseases
      (18%). Of note, 6% of those tested were diagnosed with HIV infection during their
      ED visits. CONCLUSION: Prior to the release of the 2006 Centers for Disease
      Control and Prevention guidelines for routine HIV testing in all healthcare
      settings, baseline national HIV testing rates in EDs were extremely low and
      appeared to be driven by clinical presentation.

PMID- 18832877
TI  - Influence of HIV-related immunodeficiency on the risk of hepatocellular
      carcinoma.
AB  - OBJECTIVE: To investigate HIV-related immunodeficiency as a risk factor for
      hepatocellular carcinoma (HCC) among persons infected with HIV, while controlling
      for the effect of frequent coinfection with hepatitis C and B viruses. DESIGN: A
      case-control study nested in the Swiss HIV Cohort Study. METHODS: Twenty-six HCC
      patients were identified in the Swiss HIV Cohort Study or through linkage with
      Swiss Cancer Registries, and were individually matched to 251 controls according
      to Swiss HIV Cohort Study centre, sex, HIV-transmission category, age and year at
      enrollment. Odds ratios and corresponding confidence intervals were estimated by
      conditional logistic regression. RESULTS: All HCC patients were positive for
      hepatitis B surface antigen or antibodies against hepatitis C virus. HCC patients
      included 14 injection drug users (three positive for hepatitis B surface antigen
      and 13 for antibodies against hepatitis C virus) and 12 men having sex with
      men/heterosexual/other (11 positive for hepatitis B surface antigen, three for
      antibodies against hepatitis C virus), revealing a strong relationship between
      HIV transmission route and hepatitis viral type. Latest CD4+ cell count [Odds
      ratio (OR) per 100 cells/mul decrease = 1.33, 95% confidence interval (CI) 1.06
      1.68] and CD4+ cell count percentage (OR per 10% decrease = 1.65, 95% CI 1.01
      2.71) were significantly associated with HCC. The effects of CD4+ cell count were
      concentrated among men having sex with men/heterosexual/other rather than
      injecting drug users. Highly active antiretroviral therapy use was not
      significantly associated with HCC risk (OR for ever versus never = 0.59, 95%
      confidence interval 0.18-1.91). CONCLUSION: Lower CD4+ cell counts increased the
      risk for HCC among persons infected with HIV, an effect that was particularly
      evident for hepatitis B virus-related HCC arising in non-injecting drug users.

PMID- 18832879
TI  - The 3-year renal safety of a tenofovir disoproxil fumarate vs. a thymidine
      analogue-containing regimen in antiretroviral-naive patients.
AB  - BACKGROUND: Cases of renal dysfunction in patients receiving tenofovir disoproxil
      fumarate (TDF) have been reported. We analyzed the renal safety of TDF compared
      with thymidine analogue-containing (control) regimens through 144 weeks from two
      clinical trials in antiretroviral-naive HIV-infected patients. METHODS: We
      evaluated the changes in renal parameters in 1111 patients (TDF, n = 556;
      control, n = 555) who were enrolled in two randomized, controlled trials (Studies
      903 and 934) comparing TDF vs. either stavudine or zidovudine in combination with
      efavirenz and either lamivudine or emtricitabine. The studies included patients
      with serum creatinine less than 1.5 mg/dl, serum phosphorus at least 2.2 mg/dl
      and estimated glomerular filtration rate by Cockcroft-Gault at least 60 and at
      least 50 ml/min at screening. RESULTS: Baseline characteristics were similar
      between groups. No patient discontinued due to renal abnormalities in the TDF
      arm. Through 144 weeks, the proportion of patients who experienced confirmed
      abnormalities in serum creatinine (>1.5 mg/dl) or serum phosphorus (<2.0 mg/dl)
      was less than 1% in both groups; a similar proportion of patients experienced
      urine proteinuria at least 100 mg/dl (TDF, 5%; control, 6%). The median change
      from baseline to week 144 in glomerular filtration rate was -2 and 3 ml/min by
      Cockcroft-Gault, and -2 and -1 ml/min per 1.73 m by modification of diet in renal
      disease in the TDF and control groups (P < 0.05), respectively. CONCLUSION: In
      two randomized, controlled trials, small differences in glomerular filtration
      rate over time were noted but no clinically relevant renal disease or adverse
      events were demonstrated in antiretroviral-naive patients treated with TDF
      through 144 weeks. Additional studies on renal health and renal safety in HIV are
      important goals for future clinical trials.

PMID- 18832881
TI  - Impact of small reductions in plasma HIV RNA levels on the risk of heterosexual
      transmission and disease progression.
AB  - OBJECTIVE: To estimate the impact of small changes in plasma levels of HIV-1 RNA
      on the risk of heterosexual transmission or disease progression to an AIDS
      defining event or death. DESIGN AND METHODS: We systematically reviewed the
      published literature for studies that evaluated small viral load changes among
      antiretroviral-therapy-naive, adult populations. We modeled relative risk
      estimates for viral transmission and disease progression according to 0.3, 0.5,
      and 1.0 log10 increments of HIV load. RESULTS: We calculated that the likelihood
      of transmitting HIV by heterosexual contact increased, on average, by 20% and
      that the annual risk of progression to an AIDS-defining illness or related death
      increased by 25% with every 0.3 log10 increment in HIV RNA. A 0.5 log10 increment
      in HIV RNA was associated with 40% greater risk of heterosexual transmission and
      44% increased risk of progression to AIDS or death. A 1.0 log10 increment in HIV
      RNA was associated with 100% greater risk of heterosexual transmission and 113%
      increased risk of progression to AIDS or death. CONCLUSION: Antiretroviral
      therapy continues to be unavailable or not-yet-indicated for 72% of the world's
      HIV-infected persons. Mounting evidence that treatment of coinfections may reduce
      HIV viral load, even modestly, suggests the priority of improved adjunctive care
      for HIV-infected persons even without antiretroviral therapy, both to slow
      disease progression and to reduce infectiousness.

PMID- 18832883
TI  - Spatial pattern of HIV-1 mother-to-child-transmission in Madrid (Spain) from 1980
      till now: demographic and socioeconomic factors.
AB  - OBJECTIVE: To evaluate any possible association between indicators of social
      inequalities and the geographical distribution of HIV-1 mother-to-child
      transmission (MTCT) cases in Madrid. METHODS: We carried out an observational
      survey of 224 HIV-1 vertically infected children born in 1980-2006 living in
      Madrid. We elaborated maps representing the prevalence of HIV-1 MTCT cases. We
      assessed the association between indicators of social inequalities and the
      spatial distribution of MTCT cases. Poisson univariate and multivariate analysis
      of risk factors for MTCT were performed. RESULTS: We identified core areas of
      transmission mainly in southern Madrid until 2006. The prevalence of MTCT cases
      was significantly correlated to the percentage of immigrants, illiterates,
      unemployed women and the income in 1996 and 2000/2001. The risk of MTCT increased
      in the periods up to 1996 compared with the calendar period 1980-1989, whereas
      the risk decreased in 1999-2006 [relative risk, 0.08; 95% confidence interval
      (CI), 0.03-0.18; P < 0.001]. The risk was especially high in the districts of
      Usera (absolute relative risk, 11.4; 95% CI, 2.6-49.5; P = 0.001), Puente de
      Vallecas (absolute relative risk, 14.0; 95% CI, 3.4-57.9; P < 0.001) and San Blas
      (absolute relative risk, 12.5; 95% CI, 2.9-53.6; P = 0.001). The percentage of
      illiterates was the indicator that explained the risk of MTCT (absolute relative
      risk, 1.07; 95% CI, 1.05-1.10; P = 0.001). CONCLUSION: We observed a geographic
      heterogeneity of the HIV-1 vertical transmission with the highest prevalence in
      disadvantaged districts. What is described in the present review is the HIV-1
      vertical transmission within a social context; this approach could be relevant in
      analysing the pattern of HIV-1 transmission in other Western cities or
      highlighting the distribution of other infectious diseases.

PMID- 18832884
TI  - The therapeutic phase I trial of the recombinant native HIV-1 Tat protein.
AB  - The native HIV-1 Tat protein was chosen as a vaccine candidate based on its key
      role in the virus life cycle and on the correlation of Tat-specific immune
      responses with the asymptomatic stage and lower disease progression rates, but
      also due to its sequence conservation amongst the various HIV clades as well as
      the adjuvant effects on dendritic cells. Safety, immunogenicity and efficacy data
      in monkeys support the development of this vaccine concept.

PMID- 18832882
TI  - Detection of HIV drug resistance during antiretroviral treatment and clinical
      progression in a large European cohort study.
AB  - OBJECTIVE(S): To investigate the relationship between detection of HIV drug
      resistance by 2 years from starting antiretroviral therapy and the subsequent
      risk of progression to AIDS and death. DESIGN: Virological failure was defined as
      experiencing two consecutive viral loads of more than 400 copies/ml in the time
      window between 0.5 and 2 years from starting antiretroviral therapy (baseline).
      Patients were grouped according to evidence of virological failure and whether
      there was detection of the International AIDS Society resistance mutations to
      one, two or three drug classes in the time window. METHODS: Standard survival
      analysis using Kaplan-Meier curves and Cox proportional hazards regression model
      with time-fixed covariates defined at baseline was employed. RESULTS: We studied
      8229 patients in EuroSIDA who started antiretroviral therapy and who had at least
      2 years of clinical follow-up. We observed 829 AIDS events and 571 deaths during
      38,814 person-years of follow-up resulting in an overall incidence of new AIDS
      and death of 3.6 per 100 person-years of follow-up [95% confidence interval
      (CI):3.4-3.8]. By 96 months from baseline, the proportion of patients with a new
      AIDS diagnosis or death was 20.3% (95% CI:17.7-22.9) in patients with no evidence
      of virological failure and 53% (39.3-66.7) in those with virological failure and
      mutations to three drug classes (P = 0.0001). An almost two-fold difference in
      risk was confirmed in the multivariable analysis (adjusted relative hazard = 1.8,
      95% CI:1.2-2.7, P = 0.005). CONCLUSION: Although this study shows an association
      between the detection of resistance at failure and risk of clinical progression,
      further research is needed to clarify whether resistance reflects poor adherence
      or directly increases the risk of clinical events via exhaustion of drug options.

PMID- 18832885
TI  - Rapid accumulation of nonnucleoside reverse transcriptase inhibitor-associated
      resistance: evidence of transmitted resistance in rural South Africa.
AB  - In a large cohort in rural South Africa, 73% of subtype-C-infected patients
      initiating highly active antiretroviral therapy achieved viral suppression. In
      patients with subsequent virological failure, an unexpected, rapid accumulation
      of nonnucleoside reverse transcriptase inhibitor-associated mutations was
      observed, whereas no thymidine analogue-associated mutations emerged. It appeared
      that several patients had drug-associated mutations prior to starting
      antiretrovirals, suggesting that transmission of resistance may have contributed
      to the accumulation of nonnucleoside reverse transcriptase inhibitor-mutations.
      Importantly, monitoring of HIV-RNA and prompt switch of treatment may prevent
      development of thymidine analogue-associated mutations.

PMID- 18832878
TI  - HIV-induced immunodeficiency and mortality from AIDS-defining and non-AIDS
      defining malignancies.
AB  - OBJECTIVE: To evaluate deaths from AIDS-defining malignancies (ADM) and non-AIDS
      defining malignancies (nADM) in the D:A:D Study and to investigate the
      relationship between these deaths and immunodeficiency. DESIGN: Observational
      cohort study. METHODS: Patients (23 437) were followed prospectively for 104 921
      person-years. We used Poisson regression models to identify factors independently
      associated with deaths from ADM and nADM. Analyses of factors associated with
      mortality due to nADM were repeated after excluding nADM known to be associated
      with a specific risk factor. RESULTS: Three hundred five patients died due to a
      malignancy, 298 prior to the cutoff for this analysis (ADM: n = 110; nADM: n =
      188). The mortality rate due to ADM decreased from 20.1/1000 person-years of
      follow-up [95% confidence interval (CI) 14.4, 25.9] when the most recent CD4 cell
      count was <50 cells/microl to 0.1 (0.03, 0.3)/1000 person-years of follow-up when
      the CD4 cell count was more than 500 cells/microl; the mortality rate from nADM
      decreased from 6.0 (95% CI 3.3, 10.1) to 0.6 (0.4, 0.8) per 1000 person-years of
      follow-up between these two CD4 cell count strata. In multivariable regression
      analyses, a two-fold higher latest CD4 cell count was associated with a halving
      of the risk of ADM mortality. Other predictors of an increased risk of ADM
      mortality were homosexual risk group, older age, a previous (non-malignancy) AIDS
      diagnosis and earlier calendar years. Predictors of an increased risk of nADM
      mortality included lower CD4 cell count, older age, current/ex-smoking status,
      longer cumulative exposure to combination antiretroviral therapy, active
      hepatitis B infection and earlier calendar year. CONCLUSION: The severity of
      immunosuppression is predictive of death from both ADM and nADM in HIV-infected
      populations.

PMID- 18832880
TI  - Incidence of cancer in children perinatally exposed to nucleoside reverse
      transcriptase inhibitors.
AB  - CONTEXT: Long-term studies of tolerance to perinatal exposure to antiretroviral
      nucleoside reverse transcriptase inhibitors are required, in view of the
      potential genotoxicity of some of these molecules. OBJECTIVE: To evaluate the
      incidence of cancers in uninfected children born to HIV-infected mothers. METHOD:
      Cancers were detected in a nationwide prospective cohort of children born to HIV
      infected mothers by standardized questionnaire during the prospective follow-up
      period of 2 years; thereafter, they were detected by spontaneous
      pharmacovigilance declaration and by crosschecking data with the national
      registries of childhood cancer. Standardized incidence ratio for incidence
      comparisons with general population. RESULTS: Ten cases of cancer were detected
      among the 9127 exposed HIV-uninfected children (median age: 5.4 years, 53 052
      person-years of follow-up). The overall incidence did not differ significantly
      from that expected for the general population: 10 cases observed versus 8.9 and
      9.6 expected depending on whether 1990-1999 or 2000-2004 national rates were used
      as reference [standardized incidence ratio of 1.1 (0.3-1.5) and 1.0 (0.5-1.9)].
      Five cases of central nervous system cancer were observed (standardized incidence
      ratio of 3.1 [1.0-7.2] P = 0.05 and 2.4 [0.8-5.6], P = 0.12). The relative risk
      of cancer for children exposed to didanosine-lamivudine combination was higher
      than that for zidovudine monotherapy [hazard ratio: 13.6 (2.5-73.9)]. CONCLUSION:
      This study did not evidence an overall increase in cancer risk in nucleoside
      reverse transcriptase inhibitor exposed children until 5 years of age. Results
      suggesting associations with specific nucleoside reverse transcriptase inhibitor
      combinations need further investigations. A longer surveillance, including
      differential analysis of the different cancer sites and various nucleoside
      reverse transcriptase inhibitors administered is warranted.

PMID- 18832886
TI  - Primary genotypic resistance of HIV-1 to CCR5 antagonists in CCR5 antagonist
      treatment-naive patients.
AB  - Resistance to CCR5 antagonists can be driven by mutations in gp120. Sequences
      from 323 anti-CCR5 naive patients were analyzed for the presence of previously
      described in-vivo or in-vitro resistance mutations to CCR5 antagonists located in
      the V3 loop of gp120. The V3 loop region was rather polymorphic, and 7.3% of
      patients showed viruses with combinations of mutations in V3 loop previously
      described to be involved in maraviroc resistance, a licensed CCR5 antagonist.

PMID- 18832887
TI  - Antigenic mimicry of the HIV envelope by AIDS-associated pathogens.
AB  - Only one broadly neutralizing anti-HIV antibody, 2G12, recognises the envelope
      sugars of HIV. In the present study, we show that 2G12 also recognises Candida
      albicans and Candida tropicalis with high affinity (11 nmol/l) through a
      carbohydrate-dependent interaction (50% inhibitory concentration for D-fructose,
      12 mmol/l). This is the first report of a neutralizing HIV antibody displaying
      cross-reactivity with another pathogen, revealing that the carbohydrate
      neutralization determinant of HIV, defined by 2G12, is more widespread amongst
      immunogenic, microbial surfaces than previously recognized.

PMID- 18832888
TI  - Pulmonary arterial hypertension and HIV infection.

PMID- 18832890
TI  - Abacavir-induced febrile agranulocytosis and anaemia.

PMID- 18832891
TI  - A study of rectal mucosa administration of IL-2 in treatment of HIV/AIDS: a novel
      method for the treatment of HIV/AIDS.

PMID- 18832897
TI  - Structural homology of HIV-1 GP41 and human platelet glycoprotein GPIIIa.

PMID- 18832898
TI  - Platelet GPIIb/IIIa receptor: how prone to mutation?

PMID- 18832899
TI  - Correlation of vascular endothelial growth factor with the severity of
      thalassemia intermedia.
AB  - Several lines of evidence indicate that thalassemia intermedia is associated with
      disturbances in vascular endothelial cell proliferation. In addition, autopsy
      studies of thalassemia intermedia reported obstructive lesions in the pulmonary
      artery in 44% of cases, especially splenectomized patients, and a recent in-vivo
      study reported increased level of vascular endothelial growth factor (VEGF) in
      thalassemia intermedia. The aim of the present study was to determine whether
      VEGF levels are correlated with the severity of the disease. Blood samples were
      collected from 21 patients with thalassemia intermedia and assayed for VEGF by a
      two-site enzyme-linked immunosorbent assay. A significant correlation was noted
      between VEGF levels and patient age (P = 0.0022, r = 0.82), presence of
      splenomegaly (P = 0.004, r = 0.79) and hepatomegaly (P = 0.023, r = 0.82). VEGF
      levels were also significantly correlated with both left ventricular end
      diastolic diameter and left ventricular end-systolic diameter (P = 0.02, r = 0.84
      and P = 0.01, r = 0.86, respectively). The study indicates that VEGF levels may
      be related to the clinical severity of thalassemia intermedia, as expressed by
      the degree of hepatomegaly and splenectomy and cardiac indexes. Further and
      larger studies are needed to confirm these observations.

PMID- 18832900
TI  - Vasopressin acts on platelets to generate procoagulant activity.
AB  - The aim of our study was to examine whether arginine vasopressin (AVP) is able to
      evoke in human platelets a procoagulant response due to activation of an Na+/H+
      exchanger. It was found that treatment of platelets with AVP (20-100 nmol/l)
      results in generation of a weak calcium signal, activation of Na+/H+ exchanger,
      aggregation, and development of a procoagulant response. The AVP-evoked
      procoagulant response was dose and time dependent, weaker than that produced by
      collagen or monensin (mimics Na+/H+ exchanger), and less pronounced following the
      inhibition of Na+/H+ exchanger by 5-(N-ethyl-N-isopropyl) amiloride or genistein.
      Flow cytometry studies reveal that in-vitro platelet treatment with AVP results
      in an unimodal left shift in the forward and side scatter of the entire platelet
      population, indicating morphological changes on the plasma membrane. The shift
      was dose related, weaker than that evoked by collagen, similar to that produced
      by monensin and strongly reduced in the presence of 5-(N-ethyl-N-isopropyl)
      amiloride or genistein. Using flow cytometry, we demonstrated enhanced expression
      of phosphatidylserine on the AVP-treated platelets. AVP-evoked phosphatidylserine
      exposure was dose dependent, inhibited by 5-(N-ethyl-N-isopropyl) amiloride or
      genistein and weaker than that produced by collagen. AVP in a dose-dependent
      manner produced a rise in platelet volume. The swelling was inhibited by 5-(N
      ethyl-N-isopropyl) amiloride, and its kinetics was similar to that observed in
      the presence of monensin. We conclude that prolonged treatment of platelets with
      AVP results in a procoagulant response, which may occur as a consequence of Na+
      influx mediated by Na+/H+ exchanger.

PMID- 18832901
TI  - Sex-related differences in the associations between hyperleptinemia, insulin
      resistance and dysfibrinolysis.
AB  - The adipocyte-derived hormone leptin is associated with insulin resistance and
      reduced fibrinolytic status--or dysfibrinolysis--in humans. As leptin associates
      differentially to the development of cardiovascular disease and diabetes in men
      and women, we hypothesized that leptin and insulin sensitivity are related to
      dysfibrinolysis in a sex-dependent manner. Thirty-two men and 40 women were
      recruited from the Monitoring of trends and determinants in Cardiovascular
      disease (MONICA) population sample, representing the highest and lowest quartiles
      of fasting insulin levels. Lipids, fibrinolytic status [plasminogen activator
      inhibitor 1 (PAI-1) activity, tissue plasminogen activator (tPA) mass and
      activity, and tPA-PAI complex], leptin, testosterone and sex-hormone-binding
      globulin were measured. Insulin sensitivity was estimated using the euglycaemic
      clamp technique. Body composition was determined by bioimpedance. Determinants
      for circulating levels of fibrinolytic factors were explored in a multivariate
      linear regression analysis. Levels of fibrinolytic variables and estimated
      insulin sensitivity did not differ between men and women. Leptin was
      independently associated with reduced fibrinolytic status (high PAI-1 activity,
      low tPA activity, high tPA mass, and high tPA-PAI complex) in men (P < 0.001
      0.002). In women, fat mass and/or insulin sensitivity were related to these
      factors (P < 0.001-0.03), and leptin only to reduced tPA activity (P = 0.002).
      Hyperleptinemia, dysfibrinolysis, insulin sensitivity and androgenicity associate
      differentially in men and women.

PMID- 18832902
TI  - Effect of platelet count on secretion capacity: formulization and use of the
      formulae for evaluation of platelet secretion in thrombocytopenic patients.
AB  - The correlation between platelet count and bleeding time is nonlinear. The
      bleeding time prolongs more prominently as platelet count decreases toward 10 000
      microl(-1); however, it becomes stable near 100 000 microl(-1). Clinical
      observations suggest that platelet functional capacity may also play a role in
      bleeding complications during thrombocytopenia. However, no routine method has
      been described for evaluation of platelet function during thrombocytopenia. To
      test if platelet functional capacity is affected by the cell count, as suggested
      by the platelet count-bleeding time correlation. To evaluate lumiaggregometry as
      a possible tool for studying platelet functions and prediction of bleeding in
      thrombocytopenic patients. Collagen-induced ATP release was studied in different
      dilutions of 22 healthy platelet-rich plasmas. The relationship between platelet
      count and ATP release was formulized. ATP release was also tested in 24
      thrombocytopenic (10 000-50 000 microl(-1). ) patients, and the results were
      compared with expected levels derived from the formulae. ATP release increased in
      a cubic fashion as platelet count elevated. ATP secretion values were within
      normal limits or increased in patients with idiopathic thrombocytopenic purpura.
      However, some patients with megakaryocyte deficiency had a secretion defect. ATP
      secretion was decreased in four out of seven patients with bleeding symptoms
      compared with no persons without bleeding (P = 0.003). Platelet functional
      capacity is affected by the cell count. Lumiaggregometry is potentially useful in
      evaluating platelet functions during thrombocytopenia.

PMID- 18832903
TI  - Genetic study in patients with factor XII deficiency: a report of three new
      mutations exon 13 (Q501STOP), exon 14 (P547L) and -13C>T promoter region in three
      compound heterozygotes.
AB  - A group of 29 patients with congenital factor XII (FXII) deficiency belonging to
      nine distinct families have been investigated. All were cases of true deficiency
      in the sense that there was no discrepancy between FXII activity and FXII
      antigen. From a clotting point of view, 11 patients appeared homozygous, as both
      FXII activity and antigen were very low (< or =1% and traces of antigen). In
      other words, they were cases with no cross-reactivity material. In the
      heterozygotes, FXII activity and antigen were about 50% of normal in all cases.
      The molecular studies revealed that seven patients were real homozygotes for the
      mutation -8G>C in the promoter region confirming the conclusions reported by
      coagulation tests. On the contrary, the remaining patients with a homozygote-like
      phenotype were instead found to be compound heterozygous for two distinct
      mutations. Three of these mutations were new mutations, namely the combination of
      -8G to C with 501Q to T (exon 13), 547P to L (exon 14) and -13C to T in the
      promoter, respectively. The remaining mutations seen were not new. It is
      interesting that all compound heterozygotes showed a clotting and immunological
      pattern similar to that shown by homozygotes, namely very low FXII activity and
      antigen. The new mutations were not present in the group of 98 normal persons of
      both sexes with the same geographical background. The wide diffusion of the -8G>C
      mutation in this group of patients coming from a limited geographical area
      suggests a founder effect. The significance and importance of genetic analysis in
      addition to clotting and immunological studies in FXII deficiency is emphasized.

PMID- 18832904
TI  - Comparative effects of atrial polypeptide and neurohormone C on the interaction
      of factor Xa with antithrombin III.
AB  - The effects of atrial polypeptide and neurohormone C upon the interaction of
      human factor Xa (FXa) and human antithrombin III (ATIII) were followed by sodium
      dodecyl sulfate polyacrylamide gel electrophoresis. A pattern of bands consisting
      of a 1 degree duplex complex (FXaalpha-ATIII band of 109 kDa, FXabeta-ATIII band
      of 104 kDa), a 2 degree duplex complex (alpha band of 99 kDa, beta band of 95
      kDa), a 3 degree duplex complex (alpha band of 66 kDa, beta band of 62 kDa),
      modified ATIII (ATIIIM, 58 kDa), native ATIII (55 kDa), FXaalpha (52 kDa),
      FXabeta (47 kDa), and a FXa degradation product (FXagamma, 35 kDa) was detected
      and quantitated. Preincubation of FXa, ATIII, or mixtures thereof with atrial
      polypeptide produced a shift from FXaalpha-ATIII to FXabeta-ATIII complexes and
      increases in both ATIIIM and FXagamma, reflecting degradation of the 1 degree and
      2 degree complex to form the 3 degree complex. Atrial polypeptide appeared to
      promote FXa-ATIII complex formation when preincubated with ATIII, or when added
      within 1 min to FXa/ATIII mixtures. However, when atrial polypeptide was
      preincubated with FXa, inhibition of the 1 degree complex formation was
      suggested. Upon incubation of FXa, ATIII, or mixtures thereof with neurohormone
      C, there was an increase in total complex formation, a decrease in ATIIIM, a
      decrease in FXagamma, and little change in the ratio of free FXaalpha to FXabeta,
      or the ratio of FXaalpha-ATIII to FXabeta-ATIII complexes. Therefore,
      neurohormone C may act to suppress hydrolysis or proteolytic actions of excess
      FXa on FXa-ATIII complexes, or autolytic activity of FXa, to the level of
      FXagamma via an, as yet, unknown mechanism. Additionally, neurohormone C retards
      the hydrolysis of the FXa-ATIII complexes which form free FXa and ATIIIM. Hence,
      the role of atrial polypeptide in mixtures with ATIII and in mixtures with FXa is
      quite contrasting, and may reflect mechanistic effects of the atrial polypeptide
      molecule, as well as tissue-specific reactions.

PMID- 18832905
TI  - Protein S deposition at placenta: a possible role of protein S other than
      anticoagulation.
AB  - Protein S is an antithrombotic cofactor for protein C that also has
      multifunctional anti-inflammatory, cellular protective, apoptotic and mitogenic
      properties. Protein S levels are thought to decrease during pregnancy, but the
      underlying mechanism remains unknown. We compared protein S concentrations
      throughout normal pregnancy with those of nonpregnant women and measured plasma
      C4b-binding protein levels in nonpregnant women and in pregnant women at the 40th
      gestational week. We also examined protein S and C4b-binding protein in the
      placenta by immunohistochemical staining at early (20th gestational week) and
      late (40th gestational week) stages of pregnancy. Plasma protein S activity and
      free protein S-antigen levels significantly decreased from the 10th gestational
      week and total protein S antigen decreased from the 20th. C4b-binding protein
      levels between pregnant and nonpregnant women did not significantly differ. The
      stainable portion of protein S was located at the fetomaternal interface,
      particularly at degenerative villi. C4b-binding protein was weakly stained at the
      same areas as protein S. Neither protein S nor C4b-binding protein were stained
      at normal villi. These results indicated that protein S can protect or restore
      damaged villi via a physiological effect in addition to its anticoagulation
      properties.

PMID- 18832906
TI  - A beta3 Asp217-->Val substitution in a patient with variant Glanzmann
      Thrombasthenia severely affects integrin alphaIIBbeta3 functions.
AB  - A dysfunctional Glanzmann Thrombasthenia (variant) is a rare bleeding disorder
      due to qualitative abnormalities of platelets alphaIIBbeta3 heterodimers.
      Dynamically conformational change of alphaIIBbeta3 is a complex mechanism that is
      not fully understood. For these reasons, genotyping and functional analysis of
      variant Glanzmann Thrombasthenia is important to elucidate the molecular basis of
      alphaIIBbeta3 receptor functions. In this report, we have analyzed the molecular
      effects of an A>T substitution leading to an amino acid change, D217>V, in the
      beta3 integrin gene identified in patients with variant Glanzmann Thrombasthenia.
      As the D217 residue is highly conserved among all seven beta integrin subunits
      and among beta3 integrins of different species, we tested the effect on the
      phenotype of the D217V mutation by cotransfecting the beta3 mutant (V217) or wild
      type beta3 (D217) construct with the wild-type alphaIIb into eukaryotic Chinese
      hamster ovary cells. Levels of mutant alphaIIBbeta3 heterodimers on Chinese
      hamster ovary cell surface were lightly reduced as compared with the wild type.
      Functional investigation of alphaIIBbeta3 V217 on Chinese hamster ovary cell
      surface was carried out, as fibrinogen binding, adhesion and aggregation tests
      showed a substantial reduction in respect to the control sample. Our results
      confirm ex-vivo data and suggest that the D217 amino acid is required for
      alphaIIBbeta3 receptor interactions with fibrinogen.

PMID- 18832907
TI  - Risk factors for venous thromboembolism in the elderly: results of the master
      registry.
AB  - Approximately 50-75% of patients with venous thromboembolism have a readily
      identifiable risk factor, either transient or permanent, whereas the remaining
      episodes are classified as unprovoked. The incidence of first-time venous
      thromboembolism rises exponentially with age. Whether the prevalence and the
      relative weight of major risk factors differ between elderly and younger patients
      is unclear. We performed a multicenter, prospective, observational study on
      consecutive patients with objectively confirmed acute venous thromboembolism
      admitted to 25 Italian hospitals. Baseline characteristics and information on
      temporary and permanent risk factors at the time of the index event were secured
      by an electronic data network. We enrolled 2119 patients (49.8% men), of whom 440
      (20%) were more than 75 years of age and 1679 (79.2%) 75 years of age or less.
      Elderly patients were more likely to have pulmonary embolism at presentation
      (33.6 and 25.6%, respectively, P < 0.001). After binary logistic regression
      analysis, we found that the risk of venous thromboembolism in the elderly,
      compared with the younger age group, was significantly associated with
      immobilization (odds ratio: 2.46, 95% confidence interval: 1.85-3.27) and with
      severe medical disorders (odds ratio: 1.99, 95% confidence interval: 1.41-2.80),
      whereas male sex (odds ratio: 0.53, 95% confidence interval: 0.42-0.66), surgery
      (odds ratio: 0.61, 95% confidence interval: 0.43-0.85), and trauma (odds ratio:
      0.49, 95% confidence interval: 0.31-0.77) were less common risk factors in the
      elderly than in younger patients. Use of thromboprophylaxis prior to the index
      event was not different between the two age groups. Severe medical disorders and
      immobilization are strongly associated with the occurrence of venous
      thromboembolism in the elderly. Our findings stress the need for adequate
      thromboprophylaxis in this setting.

PMID- 18832908
TI  - Hematologic effects of recombinant factor VIIa combined with hemoglobin-based
      oxygen carrier-201 for prehospital resuscitation of swine with severe
      uncontrolled hemorrhage due to liver injury.
AB  - The combination of traumatic injury, hemorrhage, and fluid resuscitation results
      in consumption and dilution of coagulation factors, adversely impacting
      hematology outcome in trauma patients. The hemostatic effects of escalating doses
      of recombinant factor VIIa added to hemoglobin-based oxygen carrier-201 were
      assessed as prehospital fluid resuscitation in swine with severe uncontrolled
      hemorrhage. Swine underwent liver injury causing severe uncontrolled hemorrhage
      and shock. During a 4-h prehospital phase, either hypotensive or tachycardic, or
      both, animals were resuscitated with hemoglobin-based oxygen carrier-201 without
      (0x) or with escalating doses of recombinant factor VIIa [90 microg/kg (1x), 180
      microg/kg (2x), or 360 microg/kg (4x)]. The animals received one initial full
      dose of 10 ml/kg at 15 min and up to four doses of 5 ml/kg thereafter. From 4 to
      72 h (hospital phase), animals received either transfusions or isotonic saline or
      both as needed. Hematology profile (complete blood count), thromboelastography,
      in-vitro bleeding (platelet function analyzer), and coagulation (prothrombin
      time) were measured and the results were compared using mixed statistical models.
      In all groups, dilutional coagulopathy was evidenced by reduced hematocrit,
      platelets, and thromboelastography-maximum amplitude, and increased platelet
      function analyzer closure time and thromboelastography-reaction time. During the
      prehospital phase, hemoglobin-based oxygen carrier-201 restored hemoglobin in all
      groups. Recombinant factor VIIa decreased prothrombin time in recombinant factor
      VIIa groups compared with the hemoglobin-based oxygen carrier-201 group (P <
      0.01). Unexpectedly, increasing recombinant factor VIIa dosage tended to increase
      fluid requirement (P > 0.05). Compared with hemoglobin-based oxygen carrier, 1x
      recombinant factor VIIa tended to decrease blood loss, lactate and
      thromboelastography-reaction time at 24 h but the 4x group increased these
      parameters. Platelets and thromboelastography-maximum amplitude decreased (P <
      0.01) with the 4x group. In swine with severe uncontrolled hemorrhage,
      prehospital resuscitation with escalating doses of recombinant factor VIIa in
      combination with hemoglobin-based oxygen carrier-201 did not change survival or
      hemostasis. However, there were trends toward possible benefits of low
      recombinant factor VIIa doses, whereas high recombinant factor VIIa doses
      adversely affected hemostasis.

PMID- 18832909
TI  - Severe factor XI deficiency in a Korean woman with a novel missense mutation
      (Val498Met) and duplication G mutation in exon 13 of the F11 gene.
AB  - Hereditary factor XI (FXI) deficiency is a rare bleeding disorder inherited in an
      autosomal recessive manner. The genetic background of FXI deficiency is the
      mutations in the F11 gene on the chromosome band 4q35. The prevalence is known to
      be particularly high in Ashkenazi Jews with well documented recurrent mutations;
      however, founder mutations in F11 have also been reported in non-Jewish patients.
      In this report, we describe a Korean patient with severe FXI deficiency whose
      causative mutations were identified by molecular genetic tests. The patient was a
      33-year-old pregnant woman. Routine gynecologic workup revealed prolonged
      activated partial thromboplastin time. Her FXI level was severely decreased at 1%
      (reference range, 60-140%). Direct sequencing analysis of the F11 gene was
      performed to identify the causative mutations. The patient was shown to have two
      different mutations, c.1546 G>A (Val498Met) and c.1560dupG (Tyr503ValfsX32) in
      the F11 gene. Val498Met is a novel missense mutation, and the Tyr503ValfsX32
      mutation was recently reported in a Japanese patient. Both mutations occurred in
      the exon 13 of F11 and were believed to disrupt the catalytic domain of the FXI
      protein, leading to severe FXI deficiency. To the best of our knowledge, this is
      the first genetically confirmed case of severe FXI deficiency in Korea, and more
      cases are needed to find any signature of founder effect in the Korean population
      and its potential relationship with other Asian populations.

PMID- 18832910
TI  - The urokinase system in patients with intermittent and persistent allergic
      rhinitis.
AB  - Local and systemic changes in hemostasis are associated with allergic diseases.
      Apart from their well documented role in regulation of plasminogen activation,
      components of the urokinase system may be involved in modulation of cellular
      activities during immune inflammatory responses. So far, little has been known
      about the function of the system in allergic inflammation. In the present study,
      we assessed circulating levels of the urokinase system components such as
      urokinase-type plasminogen activator (uPA), soluble form of uPA receptor (CD87),
      and the inhibitor--plasminogen activator inhibitor type 1. The study comprised of
      patients suffering from allergic rhinitis, however, without any asthmatic
      symptoms. Plasma levels of uPA and soluble form of uPA receptor antigens, and
      plasminogen activator inhibitor type 1 activity were measured in 17 patients with
      grass pollens-induced intermittent allergic rhinitis and 15 patients with
      persistent allergic rhinitis due to house dust mite allergy, as well as in 20 sex
      matched and age-matched healthy nonatopic participants. We did not observe any
      statistically significant differences in the levels of the urokinase system
      components between patients with intermittent allergic rhinitis and persistent
      allergic rhinitis, and the controls. The circulating levels of uPA, its soluble
      receptor, and its inhibitor did not differ between allergic rhinitis patients and
      healthy participants, therefore it seems that the systemic release and activity
      of the urokinase system molecules may be not significantly changed in the course
      of nasal allergic inflammation induced by periodic or continuous exposure to a
      natural allergen.

PMID- 18832911
TI  - Efficacy and safety of once daily low molecular weight heparin (tinzaparin
      sodium) in high risk pregnancy.
AB  - Low molecular weight heparin (LMWH) is widely regarded as the anticoagulant
      treatment of choice for the prevention and treatment of venous thromboembolism
      during pregnancy. However, previous studies have demonstrated that the
      pharmacokinetic profiles of LMWH vary significantly with increasing gestation.
      Consequently, it remains unclear whether LMWH regimens recommended for use in
      nonpregnant individuals can be safely extrapolated to pregnant women. The aims of
      this study were to assess the safety and the efficacy of tinzaparin sodium
      (Innohep) administered only once daily during pregnancy. A systematic
      retrospective review identified a cohort of 37 high-risk pregnancies which had
      been managed using tinzaparin 175 IU/kg once daily. In 26 cases, the index
      pregnancy had been complicated by development of an acute venous thromboembolism
      (17 deep vein thrombosis and nine pulmonary embolism). For each individual, case
      notes were examined and data extracted using a predetermined questionnaire. No
      episodes of recurrent venous thromboembolism were identified amongst this cohort
      of pregnancies managed using once daily LMWH administration. However, two unusual
      thrombotic complications were observed, including a parietal infarct in one
      patient, and a postpartum cerebral venous thrombosis in another. Once daily
      tinzaparin was well tolerated, with no cases of heparin-induced
      thrombocytopaenia, symptomatic osteoporosis, or foetal malformations. Tinzaparin
      dose modification based upon peak anti-Xa levels occurred in 45% of the cases
      examined. The present study is the largest study to have examined the clinical
      efficacy of once daily LMWH for use in pregnant women at high risk of venous
      thromboembolism. Our data support the safety and efficacy of antenatal tinzaparin
      at a dose of 175 IU/kg. In order to determine whether this once daily regimen
      provides equivalent (or indeed greater) thromboprophylaxis to twice daily LMWH
      regimens during pregnancy will require highly powered direct comparative studies.

PMID- 18832912
TI  - Prophylaxis with recombinant-activated factor VII (rFVIIa) for minimally invasive
      surgery in a patient with congenital factor VII deficiency: a case report with a
      single-low dose of rFVIIa.
AB  - Congenital factor VII deficiency is a rare autosomal-recessive disorder and
      surgery in patients with factor VII deficiency has been reported to be endangered
      by intraoperative or postoperative bleeding, unless a replacement therapy is
      used. In this paper, we report a successful prophylaxis with single and low dose
      rFVIIa (12.5 microg kg(-1)) in a 22-year-old homozygote factor VII deficient
      patient who underwent laparoscopic gynecologic surgery. Minimally invasive
      surgeries, such as laparoscopic surgery, could be safely performed in patients
      with congenital factor VII using single and low dose rFVIIa combined with
      vigilant clinical observation and laboratory examination.

PMID- 18832913
TI  - A novel Asp344Val substitution in the fibrinogen gamma chain (fibrinogen Caen)
      causes dysfibrinogenemia associated with thrombosis.
AB  - A 5-year-old boy was hospitalized for acute appendicitis. Routine preoperative
      hemostasis screening resulted in a diagnosis of dysfibrinogenemia. Fifteen days
      after the operation the patient was re-hospitalized for deep vein thrombosis.
      Genetic analysis of the fibrinogen genes revealed a novel missense mutation in
      exon 8 of fibrinogen gamma-chain gene (FGG): c.1031A>T, p.Asp344Val (p.Asp318Val
      in the mature chain) in heterozygosity. Interestingly, this same residue in the
      fibrinogen gamma chain was previously found to be mutated to a glycine
      (fibrinogen Giessen IV) in another young dysfibrinogenemia patient with
      thrombosis. The side chain of Asp344 (or Asp318) in the gamma chain is directly
      involved in binding to calcium. Abnormal polymerization of fibrin in fibrinogen
      Giessen IV and in the novel fibrinogen Caen described here could lead to the
      formation of abnormal clots leading to thrombosis, in addition to abnormal
      thrombin binding and decreased fibrinolysis.

PMID- 18832914
TI  - The prognostic utility of D-dimer and fibrin monomer at long-term follow-up after
      hospitalization with coronary chest pain.
AB  - D-dimer and fibrin monomer both reflect a prothrombotic potential. There are
      limited data available comparing these two markers of activated coagulation in a
      prospective manner in an unselected patient population presenting to the
      emergency department with chest pain. In addition, their role in risk
      stratification in patients with acute coronary syndrome is still under
      evaluation. Therefore, we wanted to assess the prognostic value of these markers
      with respect to long-term all-cause mortality in 871 patients admitted to the
      emergency department. Blood samples were obtained immediately following
      admission. After a follow-up period of 24 months, 123 patients had died. In the
      univariate analysis, both D-dimer and fibrin monomer predicted all-cause
      mortality within 2 years with an odds ratio of 7.78 (95% confidence interval,
      3.95-15.33) and 4.19 (95% confidence interval, 2.42-7.28), respectively, in the
      highest quartile (Q4) compared with the lowest quartile (Q1). However, in the
      multivariable logistic regression model for death within 2 years, the odds ratio
      of D-dimer and fibrin monomer was 1.80 (95% confidence interval, 0.81 to 3.97)
      and 1.04 (95% confidence interval, 0.53 to 2.04) in Q4 compared with Q1,
      respectively, and added no prognostic information above and beyond age, known
      coronary heart disease, B-type natriuretic peptide and the index diagnoses of ST
      segment elevation myocardial infarction, non-ST-segment elevation myocardial
      infarction and unstable angina pectoris. In an unselected patient population
      hospitalized with chest pain and potential acute coronary syndrome, neither D
      dimer nor fibrin monomer provided complementary prognostic information to
      established risk determinants during long-term follow-up.

PMID- 18832915
TI  - Comparative gene expression profiling in three primary human cell lines after
      treatment with a novel inhibitor of Rho kinase or atorvastatin.
AB  - Inhibitors of Rho kinase (ROCK) are a relatively new class of drugs with
      potential benefits in oncology, neurology, and fibrotic and cardiovascular
      diseases. ROCK inhibitors modulate many cellular functions, some of which are
      similar to the pleiotropic effects of statins, suggesting additive or synergistic
      properties. Studies to date have used compounds that inhibit both isoforms of
      ROCK, ROCK1 and ROCK2. This study was designed to compare gene expression
      profiles of atorvastatin with the newly developed ROCK2 inhibitor SLx-2119 in
      primary cultures of normal human endothelial cells, smooth muscle cells, and
      fibroblasts. Cells were treated with each compound for 24 h, after which total
      RNA was isolated and genome-wide gene-expression profiles were obtained with
      Illumina arrays. Because of the known effect of statins on the actin cytoskeleton
      and on connective tissue growth factor, a prominent growth factor involved in
      tissue fibrosis, the effects of SLx-2119 and atorvastatin on the actin
      cytoskeleton and connective tissue growth factor mRNA were also examined in
      cultures of smooth muscle cells with a fibrotic phenotype, isolated from biopsies
      of human intestine with radiation-induced fibrosis. Although SLx-2119 and
      atorvastatin affected expression of genes belonging to the same biological
      processes, individual genes were mostly different, consistent with synergistic or
      additive properties. Both SLx-2119 and atorvastatin reduced connective tissue
      growth factor mRNA and remodeled the actin cytoskeleton in fibrosis-derived
      smooth muscle cells, suggesting that both compounds have antifibrotic properties.
      These results form the basis for further studies to assess the possible
      therapeutic benefit of combined treatments.

PMID- 18832916
TI  - "Primary prophylaxis" with rFVIIa in a patient with severe haemophilia A and
      inhibitor.
AB  - The development of antibodies that inhibit or neutralize replacement therapy with
      factor VIII or factor IX is today the most serious complication of haemophilia
      and its treatment. Inhibitor patients have more severe joint morbidity than
      patients without inhibitors, and older adults experience significant orthopaedic
      disabilities. Because of the serious and disabling consequences of persistent
      inhibitors, there is considerable clinical and research interest in establishing
      effective bypassing agent regimens to prevent bleeding in inhibitor patients in
      much the same way as prophylaxis procedure works in noninhibitor patients. In the
      majority of these patients, the bypass agent was used as a secondary
      prophylactic. In this report, the use of recombinant factor VIIa prior to any
      clinically evident joint bleed in a patient with haemophilia A and high-titre
      inhibitor is described.

PMID- 18832917
TI  - Thrombosis of the cerebral veins and sinuses in acute promyelocytic leukemia
      after all-trans retinoic acid treatment: a case report.
AB  - Thrombosis of the cerebral veins or sinuses is a rare cerebrovascular disorder,
      which seldom represents a complication of acute promyelocytic leukemia. To the
      best of our knowledge, it never occurred during treatment with all-trans retinoic
      acid. We report a case of a 35-year-old woman affected by acute promyelocytic
      leukemia, who developed massive thrombosis of the cerebral sinuses and veins when
      she was in complete morphological and molecular remission after all-trans
      retinoic acid and idarubicin treatment. Anticoagulant therapy contributed to
      progressive dissolution of the thrombosis as documented by magnetic resonance
      imaging with complete disappearance of neurological signs without sequelae.

PMID- 18832918
TI  - Practical approach to anticoagulation for cardiopulmonary bypass in the patient
      with congenital prolonged activated partial thromboplastin time.
AB  - Patients with rare, congenital deficiencies of contact proteins (e.g., factor
      XII, prekallikrein, high-molecular-weight kininogen) present an important
      challenge with regard to safe anticoagulation during cardiopulmonary bypass.
      Specifically, activated coagulation time values are obtained with devices that
      utilize contact protein activators to generate thrombin and assess the efficacy
      of heparin-mediated antithrombin activation, with an activated coagulation time
      value of 480 s considered 'safe'. Patients with contact protein deficiencies will
      routinely have activated coagulation time values that exceed normal baseline
      values to an unpredictable extent, which, when coupled with heparin
      administration may well exceed 480 s but still potentially not reflect adequate
      antithrombin activation. We present the successful management of anticoagulation
      of a patient with either a prekallikrein or kininogen deficiency during
      cardiopulmonary bypass for coronary artery bypass graft surgery with Hepcon-based
      heparin concentration determinations. This approach, and the other alternatives
      previously mentioned, can be utilized to safely care for these rare patients in
      the setting of cardiac surgery.

PMID- 18832919
TI  - Thrombotic thrombocytopenic purpura in a patient with very early pregnancy:
      clinical presentation and autopsy findings.
AB  - Thrombotic thrombocytopenic purpura is a thrombotic microangiopathy leading to
      microvascular occlusion resulting in ischemic dysfunction of various organs.
      Pregnancy has been thought to precipitate it during second and third trimester,
      but its reports in first trimester are extremely rare. We report the clinical
      protocol of a young lady with 5-week period of gestation, who presented with
      fever, seizures and altered sensorium, and succumbed to her illness during an
      episode of seizure. Complete autopsy findings are also presented in detail.

PMID- 18832920
TI  - Gross hematuria due to acquired haemophilia in hereditary hemorrhagic
      telangiectasia.
AB  - Hereditary haemorrhagic telangiectasia (HHT, Osler-Weber-Rendu syndrome) is a
      rare inherited disease; acquired haemophilia, caused by factor VIII inhibitors,
      is a rare autoimmune disorder. Both diseases cause bleeding manifestations. We
      report a case of a young woman affected by hereditary haemorrhagic telangiectasia
      who was admitted to our unit because of gross hematuria. The prolonged activated
      partial thromboplastin time suggested us the possibility of a bleeding cause
      other than hereditary haemorrhagic telangiectasia. The test result for factor
      VIII inhibitors resulted positive and a diagnosis of acquired haemophilia was
      made. The patient was treated with frozen fresh plasma and with activated eptacog
      alpha and a steroid therapy was started. After she received steroid, factor VIII
      inhibitor titre decreased and activated partial thromboplastin time gradually
      recovered. After 2 weeks a complete normalization of activated partial
      thromboplastin time was obtained. Acquired haemophilia is a life-threatening
      disorder. Measuring factor VIII activity and its inhibitor in patients with
      bleeding and a prolonged activated partial thromboplastin time are recommended
      even in patients affected by other known hemorrhagic disease.

PMID- 18832921
TI  - Continuous intravenous infusion of a low-molecular-weight heparin during
      allogenic haematopoietic stem-cell transplantation.
AB  - Low-molecular-weight heparins are routinely administered once or twice daily by
      subcutaneous injection. With the exception of patients on haemodialysis or
      presenting with unstable angina or flat Q-wave myocardial infarction, in which
      short-term intravascular administration is recommended, little information is
      available regarding the efficacy of continuous intravenous administration of low
      molecular-weight heparins. We report the case of a 50-year-old patient who
      underwent an allogenic haematopoietic stem-cell transplantation for acute myeloid
      leukaemia. Prior to transplantation, the patient was on long-term oral
      anticoagulant (acenocoumarol) following the placement of a mechanical aortic
      valve. Acenocoumarol was stopped and low-molecular-weight heparin (nadroparin
      calcium) was administered intravenously through a continuous infusion pump (30
      000 anti-Xa U/day) starting from day 0 until day 23 after transplantation. The
      patient was prophylactically transfused with platelets when the daily platelet
      count fell below 50 x 10 l. Repeated blood measurements showed that a therapeutic
      level of anti-Xa activity was achieved and maintained at a fairly constant level.
      No haemorrhagic or thrombotic complications occurred. This observation suggests
      that intravenous continuous infusion of low-molecular-weight heparin may be an
      alternative to subcutaneous injections in selected patients who need
      anticoagulation.

PMID- 18832922
TI  - Extensive venous thrombosis following administration of high-dose
      glucocorticosteroids and tranexamic acid in relapsed Evans syndrome.

PMID- 18832925
TI  - Total body irradiation before an allogeneic stem cell transplantation: is there a
      magic dose?
AB  - PURPOSE OF REVIEW: To review the outcomes of allogeneic transplantation with
      regimens of varying total body irradiation (TBI) doses (0-1575 cGy), with an
      emphasis on reduced-intensity conditioning (RIC) regimens. RECENT FINDINGS: RIC
      regimens with a broad range of TBI doses (0, 200, 400, 550, and 800 cGy) have
      been studied. Durable donor stem cell engraftment occurred in most patients, with
      a low rate of toxicity and nonrelapse mortality. Patients excluded from
      myeloablative regimens were able to tolerate RIC regimens. Retrospective
      comparisons of patients treated with RIC and myeloablative regimens showed lower
      nonrelapse mortality but higher relapse risk with RIC; however, overall survivals
      were similar though a larger fraction of RIC patients had high-risk pretransplant
      features. Study design weaknesses limit the ability to generalize and apply these
      results. RIC and myeloablative TBI-based regimens result in durable engraftment
      of donor stem cells, tolerable toxicity, and acceptable rates of relapse risk and
      overall survival. Determination of the optimal dose of TBI for allogeneic
      transplantation is complex and depends on several variables and may vary based on
      a specific permutation of these variables. SUMMARY: A broad range of TBI doses
      for RIC regimens are effective; however, all conclusions are limited by the lack
      of prospective, randomized trials comparing RIC and myeloablative regimens.

PMID- 18832924
TI  - New advances in hematopoietic cell transplantation.
AB  - PURPOSE OF REVIEW: The present review highlights sentinel work published since
      2006 on the definition of the transplantation barrier and the elucidation of
      cytokine and immune response gene variation in defining posttransplant risks.
      RECENT FINDINGS: Recent work has defined the relative importance of matching for
      the classical human leukocyte antigen (HLA) HLA-A, HLA-B, HLA-C, DRB1, DQB1
      genes, and the importance of additive effects of multilocus disparity. This work
      provides a new framework for donor identification and extends the use of single
      locus HLA-DQB1 mismatched donors without compromising the success of the
      transplant. New data demonstrate that permissible class I mismatches may be
      defined by donor-recipient mismatching at certain residues. The concept that the
      extended HLA haplotype carries undetected but functional variation provides an
      approach for mapping novel transplantation determinants, and a means to further
      improve the clinical results of transplantation from HLA-matched unrelated
      donors. Finally, the role of sequence variation in immune response and cytokine
      genes provides a means for assessing risks for a given transplant recipient and
      may aid in the planning of the transplant procedure. SUMMARY: Optimizing the
      results of unrelated donor transplantation requires an understanding of risks
      associated with variation of HLA genes within the major histocompatibility
      complex, and of genes that participate in the immune response and inflammatory
      pathways.

PMID- 18832926
TI  - Unmanipulated or CD34 selected haplotype mismatched transplants.
AB  - PURPOSE OF REVIEW: Unmanipulated or CD34 selected haplotype mismatched
      transplantation provides the benefits of hematopoietic stem cell transplant for
      nearly all patients who do not have a human leukocyte antigen fully matched
      sibling or who urgently need transplantation. Haplotype mismatched transplant is,
      however, complicated by delayed immune reconstitution, leading to increased risks
      of fatal posttransplant opportunistic infections. This review summarizes recent
      investigations aimed at optimizing outcomes. RECENT FINDINGS: The graft is a
      megadose of positively/negatively T-cell-depleted or unmanipulated progenitor
      cells. Although haploidentical transplant modalities are based mainly on high
      intensity conditioning regimens, recently introduced reduced-intensity regimens
      showed promise in decreasing early transplant-related mortality and in extending
      the opportunity of hematopoietic stem cell transplantation to an elderly
      population with more comorbidities. Natural killer cell alloreactivity reduces
      graft-versus-host disease while augmenting graft-versus-malignancy. Immune
      reconstitution was highly predictive of outcome following T-cell-depleted
      transplantation. SUMMARY: Mismatched/haploidentical transplant provides an
      alternative approach for patients with high-risk hematological malignancies or
      marrow failure syndromes. Overall survival and clinical outcome continue to
      improve. Future challenges lie in determining the safest preparative conditioning
      regimen, minimizing graft-versus-host disease while preserving effective graft
      versus-malignancy and promoting rapid immune reconstitution.

PMID- 18832927
TI  - Unrelated donor umbilical cord blood transplantation for the treatment of
      hematologic malignancies.
AB  - PURPOSE OF REVIEW: This review summarizes the state of the art of unrelated donor
      (URD) umbilical cord blood transplantation (UCBT) for the treatment of
      hematologic malignancies and discusses the current issues associated with the use
      of this hematopoietic stem cell (HSC) source. RECENT FINDINGS: In contrast to the
      very high transplant-related mortality associated with the early experience of
      UCBT, recent series have been associated with comparable survival to that of
      human leucocyte antigen-matched URD transplantation in children with similarly
      promising results in adults with the use of double-unit grafts. In addition,
      utilization of reduced-intensity conditioning regimens has been successful
      extending access to patients unsuitable for myeloablation. Consequently, the use
      of umbilical cord blood as a HSC source and the global inventory of units in
      public banks is rapidly increasing although challenges associated with
      engraftment, unit quality, and infectious complications remain and will be
      discussed in this review. SUMMARY: URD umbilical cord blood is an alternative HSC
      source offering a unique set of advantages and disadvantages as compared with the
      transplantation of HSC from unrelated volunteers. Improved transplant outcomes
      are now making UCBT a rival to URD transplantation for the treatment of
      hematologic malignancies.

PMID- 18832928
TI  - Epstein-Barr virus-associated lymphoproliferative disease after allogeneic
      haematopoietic stem cell transplantation: molecular monitoring and early
      treatment of high-risk patients.
AB  - PURPOSE OF REVIEW: Epstein-Barr virus-associated lymphoproliferative disease (EBV
      LPD) is a rare but serious complication in recipients of allogeneic stem cell
      transplants. An overview is given of the incidence, monitoring and (early)
      treatment of EBV-LPD. RECENT FINDINGS: The most important risk factor for EBV-LPD
      is the use of in-vivo T-cell depletion with antithymocyteglobulin. In addition,
      alternative donor stem cell transplantation is associated with an increased risk
      for EBV-LPD. Monitoring of EBV DNA in high-risk patients and subsequent early
      treatment is very successful, resulting in a low EBV-associated mortality. The
      monitoring of EBV-specific cytotoxic T lymphocytes might further increase the
      positive predictive value of EBV DNAemia for EBV-LPD. Once overt EBV-LPD has been
      diagnosed, rituximab treatment is indicated, guided by monitoring of EBV DNA. The
      infusion of donor lymphocytes is highly effective, but may be complicated by
      graft-versus-host disease. Therefore, the infusion of T cells, which have been
      depleted of alloreactive cells, is currently receiving attention. SUMMARY: EBV
      DNA levels should be monitored in patients with high-risk features. Early
      treatment may be instituted at predefined DNA levels (preemptive approach) or at
      the earliest signs of LPD (prompt approach). Stepwise treatment guided by EBV
      DNA, including interruption of immunosuppression, rituximab, and adoptive T-cell
      immunotherapy may all add to the low mortality currently associated with LPD
      following allogeneic stem cell transplantation.

PMID- 18832929
TI  - Invasive aspergillosis: diagnosis, prophylaxis and treatment.
AB  - PURPOSE OF REVIEW: Invasive aspergillosis is a common cause of morbidity and
      mortality in hematopoietic stem cells transplant recipients. Owing to its
      intrinsic high mortality rate, early diagnosis and treatment are critical. This
      review will therefore address the most important recent advances in diagnosing,
      preventing and treating invasive aspergillosis in hematopoietic stem cells
      transplant. RECENT FINDINGS: The present review will focus on therapeutic and
      prophylactic aspects, with particular regard to clinical use of drugs other than
      voriconazole (which has a well known and consolidated role for first-line
      therapy), combination therapy and prophylactic regimens, particularly with
      posaconazole. This review will also briefly deal with the clinical role of
      diagnostic tests such as the detection of galactomannan in body fluids other than
      blood, beta-D-glucan in serum and fungal DNA by PCR in body fluids. SUMMARY:
      Galactomannan antigen detection is a rather reliable diagnostic test for invasive
      aspergillosis, particularly when a lower threshold of sensitivity is used. PCR is
      still to be validated. Liposomal amphotericin B at 3 mg/kg per day showed a
      similar efficacy in invasive aspergillosis as reported for voriconazole.
      Therapeutic drug monitoring of Aspergillus-active azoles should be implemented
      whenever possible in order to maximize the antifungal effect and minimize
      toxicity. Posaconazole showed to be active in prophylaxis, though its
      effectiveness in the global patient population is still controversial.

PMID- 18832930
TI  - Haematopoietic stem cell transplantation for autoimmune disorders.
AB  - PURPOSE OF REVIEW: To summarize recent evidence and current trends in the use of
      haematopoietic stem cell transplantation (HSCT) for autoimmune diseases. RECENT
      FINDINGS: Updates of published trials and data from the registries indicate a
      long-lasting, immunosuppression-free condition in about 50% of the patients who
      underwent an HSCT for a severe, progressive autoimmune disease. For all diseases,
      autologous HSCT is largely preferred for safety reasons, whereas allogeneic HSCT
      is to be considered only for carefully selected cases. Transplant-related
      mortality (TRM) has decreased in the past 5 years, due to both better selection
      of patients and the use of less intensive conditioning regimens. The most
      employed conditioning regimens in Europe are BCNU (carmustine), etoposide, ARA-C
      (cytosine arabinoside), M (melphalan) (BEAM)/anti-thymocyte globulin in multiple
      sclerosis and high-dose cyclophosphamide/anti-thymocyte globulin for all other
      diseases, with a trend for more intense regimens in North America. Multiple
      sclerosis and systemic sclerosis are currently the most frequent diagnoses.
      Prospective comparative trials are currently ongoing both in Europe and North
      America. SUMMARY: Recent reports confirm the evidence that HSCT is able to induce
      a high rate of sustained remissions in most severe autoimmune diseases,
      unresponsive to conventional treatments. Valuable information is expected by the
      finalization of the ongoing prospective, comparative trials.

PMID- 18832931
TI  - Lessons learned from mouse models of hemolytic transfusion reactions.
AB  - PURPOSE OF REVIEW: Hemolytic transfusion reactions (HTRs) are potentially fatal
      complications of blood transfusions. Many studies, primarily performed in vitro,
      have provided a great deal of insight into the initiating events of HTRs;
      however, it is not clear how they are modulated and how they combine to lead to
      one or more of the final common pathways. Recently developed mouse HTR models now
      make it possible to enhance our understanding of the pathogenesis of HTRs; this
      will allow for the rational design of specific therapies to prevent or ameliorate
      this serious complication in transfusion medicine. RECENT FINDINGS: Mouse models
      support the hypothesis that 'cytokine storm' plays an important role in the
      pathogenesis of HTRs. Nitric oxide and endothelial cell dysfunction are also
      implicated in the pathophysiology of these reactions. In addition, the intriguing
      phenomenon of 'antigen loss,' in which antigen crosslinking by alloantibody leads
      to antigen removal rather than red blood cell clearance, has been modeled and
      explored. Finally, these mouse models were used to evaluate new therapeutic
      targets employing complement receptor 1 peptide homologues and the antimacrophage
      agent, liposomal clodronate. SUMMARY: Models of HTRs are valuable for gaining a
      better understanding of the pathophysiology of these potentially fatal
      complications of blood transfusion. The participation of various inflammatory
      mediators was shown to play a role in these reactions in vivo. This knowledge
      will lead to novel treatment options.

PMID- 18832932
TI  - Glycans and glycosylation of platelets: current concepts and implications for
      transfusion.
AB  - PURPOSE OF REVIEW: Platelet products are currently stored at room temperature,
      because refrigeration causes their rapid clearance from the circulation upon
      transfusion. Glycans have recently been emphasized as important determinants for
      the clearance of refrigerated platelets. The present review addresses the current
      knowledge of platelet glycans and the potential of glycosylation for improving
      platelet storage. RECENT FINDINGS: Removal of refrigerated platelets from the
      circulation is partly mediated by recognition of clustered beta-N
      acetylglucosamine on platelet surface glycoproteins by the alphaMbeta2 hepatic
      lectin receptor. Capping the exposed beta-N-acetylglucosamine residues by
      enzymatic galactosylation restored the circulation of short-term chilled murine
      platelets, introducing a novel method that allows for cold storage of platelet.
      Recent studies have, however, shown that galactosylation is not sufficient to
      restore circulation of long-term refrigerated platelets. Additional data indicate
      that differential carbohydrate-mediated mechanisms may exist for clearance of
      short-term and long-term cold-stored platelets. SUMMARY: Room temperature storage
      of platelet products increases the risk of transfusion-mediated sepsis and
      accelerates platelet deterioration, limiting platelet shelf life. Recent evidence
      suggests that glycoengineering of platelets might allow for their cold storage,
      significantly improving the quality of platelet products.

PMID- 18832933
TI  - Indications for use and cost-effectiveness of pathogen-reduced ABO-universal
      plasma.
AB  - PURPOSE OF REVIEW: Donor selection and viral screening methods combined with
      pathogen reduction have increased the safety of pooled plasma to a level which
      makes reintroduction of ABO-universal plasma an important option. RECENT
      FINDINGS: Solvent detergent-treated pooled plasma has proved to be well suited
      for the production of pathogen-reduced ABO-universal plasma. One such product,
      Bioplasma FDP, was licensed in South Africa in 1994 and has since 1996 been in
      successful clinical use. A clinical study with this product and two studies with
      the European product, Uniplas, have confirmed the efficacy and safety of pathogen
      reduced ABO-universal plasma. SUMMARY: Pooling of plasma enables the production
      of ABO-universal plasma. Pathogen reduction with solvent detergent eliminates
      lipid-enveloped viruses, whereas neutralizing antibodies in the plasma pool and
      nucleic acid amplification testing ensures the safety for recognized nonlipid
      enveloped viruses. Pooling also eliminates transfusion-associated acute lung
      injury (the leading cause of plasma transfusion-related death), reduces
      immunologic/allergic adverse events by 60-80% and standardizes plasma protein
      content. Thus, in addition to ABO compatibility, pathogen-reduced ABO-universal
      plasma has important supplementary benefits that improve the product's cost
      effectiveness.

PMID- 18832934
TI  - Blood grouping discrepancies between ABO genotype and phenotype caused by O
      alleles.
AB  - PURPOSE OF REVIEW: In the modern transfusion service, analysis of the ABO allele
      underlying a donor or recipient's A or B subtype phenotype is becoming a
      mainstream adjunct to the serological investigation. Although an analysis of the
      ABO gene can be helpful in establishing the nature of the subtype phenotype,
      numerous confounding factors exist that can lead to a discrepancy between the
      genotype and the observed phenotype. RECENT FINDINGS: Although the most common
      group O alleles share a common crippling polymorphism, a growing number of
      alleles feature other polymorphisms that render their protein nonfunctional yet
      are similar enough to the consensus A allele that an errant phenotype would be
      predicted from the genotype, if the genotyping method was not specifically
      designed for their detection. Some of these O alleles might actually encode a
      protein with weak and variable A antigen synthetic ability. SUMMARY: ABO
      genotyping can be a powerful asset in the transfusion service, but a thorough
      knowledge of the confounding factors that can lead to genotype/phenotype
      discrepancies is required.

PMID- 18832935
TI  - Structure, function and significance of Rh proteins in red cells.
AB  - PURPOSE OF REVIEW: The present article reviews recent data concerning the
      structure and function of the Rh-associated glycoprotein (RhAG) and considers
      what can be inferred about the structure and functional significance of the D and
      CE polypeptides. RECENT FINDINGS: The structure of a bacterial RhAG (from
      Nitrosomonas europaea) has been solved and its gas channel elucidated. This
      information allows us to model a more accurate structure of RhD and RhCE
      polypeptides than has been possible hitherto. Human RhAG has been shown to act as
      a gas channel for CO2. SUMMARY: Elucidation of the structure of a bacterial RhAG
      allows us to model the structure of D and CE polypeptides more accurately than
      before. Results suggest that whereas RhAG has a channel for passage of neutral
      gases (CO2, NH3 and possibly oxygen and nitric oxide), D and CE polypeptides are
      unlikely to have a transport function.

PMID- 18832936
TI  - The role of inflammation in alloimmunization to antigens on transfused red blood
      cells.
AB  - PURPOSE OF REVIEW: To discuss how inflammation affects humoral alloimmunization
      to antigens on transfused red blood cells (RBCs). RECENT FINDINGS: Recently,
      three unique murine models of humoral alloimmunization to transfused RBCs have
      been described. As in humans, RBC alloimmunization rates in recipient mice are
      variable, with segregation into responder and nonresponder groups. Because the
      recipient mice are genetically identical, environmental factors may play a role
      in regulating alloimmunization. These models have further been used to
      demonstrate that recipient inflammation has a complex regulatory effect upon
      alloimmunization. Isolated case reports in humans raise the possibility of a
      similar role of inflammation in regulating alloimmunization to RBCs. SUMMARY: It
      is currently unknown why some human transfusion recipients mount strong
      alloantibody responses, whereas others do not. Human leukocyte antigen
      immunogenetics likely play a substantial role. However, within groups with the
      genetic capacity to respond to a given RBC antigen, recipients still segregate
      into responders and nonresponders. The data reviewed herein indicate that
      recipient inflammation in mice has the capacity to regulate alloimmunization.
      Future studies will be required to further understand these effects and to
      investigate if similar biology regulates alloimmunization to transfused RBCs in
      humans.

PMID- 18832937
TI  - Current world literature.

PMID- 18832938
TI  - Reconstructive urology.

PMID- 18832939
TI  - Robotic renal and upper tract reconstruction.
AB  - PURPOSE OF REVIEW: To evaluate the current role of robotic surgery in upper
      urinary tract reconstruction. RECENT FINDINGS: Robotic techniques have been
      increasingly adopted by urologists for reconstruction of the upper urinary tract.
      The improved dexterity, visualization, and ergonomics of robotic systems have
      applied naturally to reconstruction and have facilitated intracorporeal suturing
      compared with traditional laparoscopy. In particular, robotic techniques have
      been used for anastamotic suturing during minimally invasive pyeloplasty. Series
      of robotic pyeloplasty have demonstrated comparable long-term outcomes to
      laparoscopy, a shorter learning curve, subjective operator benefits, and
      potential advantages in operative time. Other robotic reconstructive procedures
      of the upper tract have included ureterocalicostomy, ureteroureterostomy,
      ureterolysis, and ureteral reimplantation with and without psoas hitch. SUMMARY:
      Robotic techniques provide clear advantages for minimally invasive upper tract
      reconstruction, though the objective benefits need further delineation. These
      procedures are in their early experience, and larger series with prospective
      randomized comparison with the standard of care are warranted. Low volume of
      upper tract reconstruction in general will likely require multi-institutional
      study. Continued study of cost-effectiveness is necessary to define the optimal
      role for robotic reconstruction in both medical and economic terms.

PMID- 18832940
TI  - Current status of tissue engineering in urology.
AB  - PURPOSE OF REVIEW: Tissue engineering is a rapidly advancing technology that is
      shifting from the laboratory to urological practice. The review explores recent
      developments and considers the relationship to existing treatments. RECENT
      FINDINGS: Different strategies to generate transplantable tissue grafts in vitro
      and harness host regenerative processes for integration of grafts and
      biomaterials in vivo are common themes in the recent literature. Highlights
      include dynamic cell culture to precondition grafts and the use of omental
      wrapping to promote vascularization. Emphasis on specific cell culture conditions
      is set to shift towards the monitoring of differentiation and functional outcome.
      The future might encompass the use of stem cells to overcome the issues of
      harvesting cells from diseased tissues. Improved understandings of scaffold and
      cell interactions are particularly important to advance graft development and
      outcome. Recent trials give some indication of clinical outcome for tissue
      engineered treatments, but patient benefit could be difficult to interpret in
      salvage cases. SUMMARY: Tissue engineering applications can be broken down into
      tissue- or organ-based approaches, only through examining these in clinical
      settings can potential success can be judged. Treatments must be appropriately
      evaluated for risk/benefit in comparison to existing treatments. This approach
      requires open and robust debate amongst clinicians and scientists.

PMID- 18832941
TI  - Salvage surgery for bladder outlet obstruction after prostatectomy or cystectomy.
AB  - PURPOSE OF REVIEW: Obstruction of the outlet secondary to a recurrent bladder
      neck contracture postprostatectomy or cystectomy presents a reconstructive
      challenge combined with the goal of restoring normal lower urinary tract
      function. The majority of bladder neck contractures are responsive to urethral
      dilation or cold knife direct visual internal urethrotomy. Urethral stents and
      anastomotic urethroplasty have been used with increasing frequency to regain
      urethral continuity. In the postcystectomy patient, obstruction due to stricture
      must be differentiated from dysfunctional voiding - unfavorable pouch voiding
      mechanics, insufficient pouch pressure generation or failure of external
      sphincter relaxation. RECENT FINDINGS: Aggressive electrocautery resection with
      urethral stent placement and anastomotic urethroplasty are viable options for
      achieving patency after bladder neck obstruction. For those desirous of achieving
      a continent endpoint, artificial urinary sphincter should be planned as a second
      stage procedure after stabilization of the bladder neck. Creation of a
      catheterizable limb remains an option for the unreconstructable urethra. If
      augmentation cystoplasty is necessary due to storage pressure abnormalities, an
      appendicovesicostomy or reconfigured ileum segment is a reasonable method to
      achieve continence. SUMMARY: The incidence of recurrent obstruction due to tissue
      in-growth or stricture is similar between urethral stent placement and
      anastomotic urethroplasty, respectively. The high incontinence rate after either
      initial treatment should be expected and factored into the overall treatment
      plan.

PMID- 18832942
TI  - The prepuce: preservation and reconstruction.
AB  - PURPOSE OF REVIEW: To analyze the role of prepuce preservation in various
      disorders and discuss options available to reconstruct the prepuce. RECENT
      FINDINGS: The prepuce can be preserved in selected cases of penile degloving
      procedures, phimosis or hypospadias repair, and penile cancer resection. There is
      no clear evidence that debilitating and persistent preputial lymphedema develops
      after a prepuce-sparing penile degloving procedure. In fact, the prepuce can at
      times be preserved even if lymphedema develops. The prepuce can potentially be
      preserved in both phimosis and hypospadias repair. Penile cancer localized to the
      prepuce can be excised using Mohs' micrographic surgery without compromising
      survival. Reconstruction of the prepuce still remains a theoretical topic. There
      has been no study that has systematically evaluated efficacy of any
      reconstructive procedures. SUMMARY: The standard practice for preputial disorders
      remains circumcision. However, prepuce preservation is often technically feasible
      without compromising treatment. Preservative surgery combined with reconstruction
      may lead to better patient satisfaction and quality of life.

PMID- 18832943
TI  - Penile enlargement.
AB  - PURPOSE OF REVIEW: As male genital corrective surgery is becoming increasingly
      requested by patients, the need to reach a general consensus on indications and
      techniques is now imperative. This review of published data provides an overview
      concerning patient selection modalities, benefits/risks and expected outcomes of
      surgery. Finally, the article focuses on ethical issues caused by the growing
      aesthetic nature of this surgery. RECENT FINDINGS: Interest has been sparked by
      animal studies, the description of innovative techniques for lengthening and
      girth enhancement techniques, reconstructive phalloplasty and penile implant
      surgery. Data suggest that better objective surgical outcomes are possible,
      though in many cases long-term data and patient-rated satisfaction details are
      lacking. Most importantly, studies show the importance of having a
      multidisciplinary team in charge of patient selection. SUMMARY: Although more
      long-term data are required before a general consensus can be reached, recent
      findings point to the absolute need for a thorough psychological assessment of
      men requesting penile enhancement surgery. Urologists should work in very close
      collaboration with psychologists or psychosexologists both during the
      preoperative phase (to verify eligibility for surgery) and afterwards (to provide
      counselling).

PMID- 18832944
TI  - Penile reconstruction/formation.
AB  - PURPOSE OF REVIEW: To evaluate current reviews and assess scientific validity of
      the recent literature on penile reconstruction after trauma, penile
      reconstruction in gender reassignment surgery, concealed penis, and aphallia.
      RECENT FINDINGS: Technical advances in penile reconstruction have been
      highlighted. The few long-term follow-up studies available confirm the difficulty
      of such surgery, in terms of complications and the limits of the final achievable
      outcomes. The surgery necessitates several steps and a high number of revisions.
      Scientific progress in penile reconstruction seems slow, with a lack of
      controlled studies, high rate of loss to follow-up (especially in sex
      reassignment surgery) and a lack of validated assessment measures. However, a few
      recent studies are making the problems clearer, especially in patient selection
      and the avoidance of raising false expectations in patients.

PMID- 18832945
TI  - Radioactive iodine (131I) effects on male fertility.
AB  - PURPOSE OF REVIEW: Radiometabolic therapy with radioactive iodine (I) is the
      standard treatment for differentiated thyroid cancer and is also currently the
      treatment of choice for Graves' disease in the United States. and in most
      countries. Men younger than 40 years of age represent about 10% of all
      radiometabolic treatments. Thus, the question arises whether I therapy is able to
      induce a damage to the fertility potential. RECENT FINDINGS: The different
      effects caused by I therapy employed in cancer and hyperthyroid patients are
      reviewed. Most articles about the first category of patients show a damage to the
      germinal epithelium directly related to the cumulative dose delivered. Although
      the small amounts used in hyperthyroidism are usually well tolerated in terms of
      sterility risk, the impairment caused by hyperthyroidism per se is probably
      higher than that caused by I treatment. SUMMARY: Young cancer patients,
      particularly those with node or lung metastases, who will probably undergo
      repeated treatments should be aware of the potential risks to their fertility. An
      evaluation of testicular function is thus advisable. When an impairment of
      fertility potential is already present, the option of freezing semen should be
      considered. The available studies concerning I therapy in hyperthyroidism suggest
      that this treatment does not cause a worsening of semen analysis but an
      amelioration in affected patients.

PMID- 18832946
TI  - Follicle-stimulating hormone treatment of male infertility.
AB  - PURPOSE OF REVIEW: Treatment with gonadotrophins is very effective in patients
      affected by hypogonadotrophic hypogonadism. The success of follicle-stimulating
      hormone (FSH) treatment in these men has brought the utilization of the same
      therapy in infertile oligozoospermic patients, aimed at obtaining a quantitative
      increase in sperm count. RECENT FINDINGS: FSH plays a crucial role in human
      reproduction. This physiological role in spermatogenesis has induced various
      attempts to treat idiopathic oligozoospermic men with FSH, often inducing the
      restoration of normal spermatogenesis and spontaneous pregnancy. However, the
      results obtained so far are still controversial. In this research, attention is
      focused on the possible criteria able to predict a seminal response to the
      specific hormonal treatment. Moreover, we have correlated different polymorphisms
      of FSH receptor gene with the outcome of FSH treatment. In this article, the
      literature is reviewed, and the authors' experience on using FSH treatment in
      oligozoospermic patients is discussed. SUMMARY: FSH treatment may represent a
      valid tool for infertile men. However, it should be performed on selected
      patients utilizing some predictive parameters able to identify a priori responder
      patients with high probability.

PMID- 18832947
TI  - Adult varicocele.
AB  - PURPOSE OF REVIEW: Adult varicocele presents a challenge for male reproductive
      specialists. We have yet to fully elucidate the pathophysiology of varicocele.
      The enigma of the varicocele, although a source of frustration for clinicians,
      has been a siren call for researchers as attested to by the substantial, if
      flawed body of literature on the topic. We critically review recent publications
      on varicocele. RECENT FINDINGS: Although yielding mixed results, studies this
      year have explored the potential relationship between oxidative stress and
      varicocele-associated infertility. In clinically focused research, one group
      tackled the contentious question of efficacy of surgical varicocele management.
      Building on the errors of prior meta-analyses, this study takes a fresh view on
      an old but vital topic. Finally, it is becoming clearer that varicocele affects
      Leydig cell function as well as seminiferous tubular function, and is a risk
      factor for androgen deficiency. SUMMARY: With exceptions, recent studies support
      a role for varicocelectomy in the management of infertile couples. In addition,
      evidence is accumulating that early repair of varicoceles, especially large
      varicoceles, may be effective in preventing future infertility and may be an
      effective treatment for androgen deficiency.

PMID- 18832948
TI  - Penile rehabilitation following radical prostatectomy.
AB  - PURPOSE OF REVIEW: Erectile dysfunction is common after radical prostatectomy.
      Erectile dysfunction has a negative impact on health-related quality of life.
      Penile rehabilitation is defined as the use of any drug or device at or after
      radical prostatectomy to maximize erectile function recovery. This is an up-to
      date review of the current state of science supporting penile rehabilitation
      after radical prostatectomy. RECENT FINDINGS: The purpose of penile
      rehabilitation is to prevent corpus cavernosal smooth muscle structural
      alterations to not only maximize the chances of a man to recover functional
      erections but also return him to his preoperative erectile function level.
      Current animal and human data support the use of PDE5 inhibitor and the
      generation of early erections after radical prostatectomy as a strategy to
      improve erectile function recovery. The magnitude of this improvement is
      currently unclear. SUMMARY: The results from animal and human studies imply that
      the use of PDE5 inhibitor and the generation of erections early after radical
      prostatectomy are of some benefit to erectile function recovery. Although the
      definitive protocol for rehabilitation is not defined, future work is aimed at
      determining this.

PMID- 18832949
TI  - New concepts in Klinefelter syndrome.
AB  - PURPOSE OF REVIEW: Klinefelter syndrome, 47,XXY and its variants, is the most
      common chromosomal aberration among men, with estimated frequency of 1: 500 among
      newborns. Men with Klinefelter syndrome present with sequels of hormonal and
      spermatogenic testicular failure like infertility, low testosterone, erectile
      dysfunction, and low bone mineral density. This review is aimed to provide the
      practicing urologist with an important source of clinically relevant information
      about Klinefelter syndrome. RECENT FINDINGS: Sperm can be found in over 50% of
      men with Klinefelter syndrome, thus men with Klinefelter syndrome are not
      sterile. Recent evidence suggests that children with Klinefelter syndrome are
      born with spermatogonia and lose large numbers of germ cells during puberty.
      Early diagnosis and treatment can improve the quality of life and the overall
      health of men with Klinefelter syndrome. SUMMARY: Growing interest in Klinefelter
      syndrome among translational scientists and clinicians will result in better
      understanding of the pathophysiology of testicular failure. In some states,
      screening programs for Klinefelter syndrome are already in place, which will
      increase the number of patients with Klinefelter syndrome seen by practicing
      urologists in the near future. Diagnosis and management of patients with
      Klinefelter syndrome is within the scope and training of urologists. Development
      of randomized clinical trials comparing different forms of interventions in men
      and children with Klinefelter syndrome will allow us to standardize the care of
      these patients.

PMID- 18832950
TI  - The Y chromosome and male infertility.
AB  - PURPOSE OF REVIEW: Therapies for the treatment of severe male factor infertility
      have advanced well beyond our knowledge of the conditions we are treating. An
      intact Y chromosome is necessary for optimal spermatogenesis. It is imperative
      for the clinician to understand the molecular basis and clinical implications of
      anomalies that might afflict the Y chromosome. RECENT FINDINGS: The molecular
      geography of the Y chromosome has recently been described, allowing correlations
      to be made to various clinical states of severe spermatogenic compromise.
      Microdeletions of parts of the Y chromosome are found in a small number of men
      with spermatogenic failure involving, predominantly, three regions termed AZFa,
      AZFb, and AZFc. SUMMARY: It is necessary that a Y chromosomal microdeletion assay
      be carried out prior to any intervention using ejaculated sperm or prior to any
      surgical procedure to try to find spermatozoa in an azoospermic man.

PMID- 18832951
TI  - Bibliography. Current world literature. Reconstructive surgery.

PMID- 18832954
TI  - "Ignoramics" in medical and premedical education.
AB  - As physician-essayist Lewis Thomas has urged, ignorance-based courses and
      curricula are urgently needed in medical education to prepare future generations
      of scientific physicians and physician-scientists for the uncertain, rapidly
      changing world ahead. This article reviews the evolving concept of ignorance in
      general and specifically in medicine and its relationship to knowledge. Issues
      about goals, content, and assessment of such ignorance-based courses are
      discussed along with the experience of the University of Arizona's National
      Institutes of Health-sponsored Summer Institute on Medical Ignorance for medical
      student researchers and disadvantaged high school students. Summer Institute on
      Medical Ignorance activities can be readily replicated or adopted in their
      entirety or partially in both live and Internet-based formats. These will serve
      to introduce medical ignoramics and questioning as a way to balance the
      information-overloaded medical curriculum.

PMID- 18832956
TI  - The art of treatment.

PMID- 18832957
TI  - Safety evaluation of the concomitant use of clozapine and benzodiazepines: a
      retrospective, cross-sectional chart review.
AB  - OBJECTIVE: Previously published case reports have noted severe adverse reactions
      such as cardiac arrest, respiratory arrest, and sudden death when clozapine (CLZ)
      and benzodiazepines (BZDs) are used concomitantly. As CLZ and BZD are both used
      regularly to treat psychiatric illness, it is important to have additional
      information concerning this potential interaction. The objective of this study
      was to contribute to the evolving literature by evaluating the occurrence of
      sudden deaths and cardiac or respiratory events leading to death in patients
      treated concurrently with CLZ and BZD. METHOD: A retrospective chart review was
      conducted at a 240-bed New York State mental health facility. Most patients in
      this facility have been diagnosed with refractory schizophrenia, resulting in
      high rates of CLZ use. Electronic and hard copy records of the 490 patients who
      had been treated with CLZ in this facility at any time from 2001 to 2006 were
      selected, and the medication records of these patients were assessed for
      concomitant BZD use. Information on 152 patients who were treated with CLZ and a
      BZD concomitantly during this time period are included in this study. Data from
      the facility's mortality review committee were obtained to determine sudden
      deaths and cardiac or respiratory events leading to death in patients treated
      with CLZ and BZD concomitantly. Secondary parameters also recorded during the
      chart review included average duration of CLZ therapy, BZD therapy, and
      concomitant therapy; average doses of agents used; specific BZD used; number of
      patients treated with a specific BZD; psychiatric diagnosis; and use of other
      medications that depress the central nervous system. RESULTS AND CONCLUSIONS: No
      deaths occurred as a result of concomitant BZD and CLZ use in the sample examined
      in this study, suggesting that CLZ and BZD may be safely used concomitantly in
      many cases. Further study is needed to determine patient characteristics or
      predisposing factors that might put patients at higher risk of death from this
      interaction. Our findings are limited by the small sample size and suboptimal
      frequency of side effect measurements (e.g., measurements of blood pressure and
      heart rate, reports of hypotensive episodes). Confounding variables that might
      also play a role in interactions between CLZ and BZDs, but which were not
      measured in this study, include other types of respiratory compromise, cognitive
      dysfunction, and organ dysfunction. Precautionary measures that may be used when
      initiating concomitant CLZ and BZD therapy include slow titration of CLZ, blood
      pressure monitoring, and/or nightly pulse oximeter measurements.

PMID- 18832958
TI  - An open pilot study of the combination of escitalopram and bupropion-SR for
      outpatients with major depressive disorder.
AB  - OBJECTIVE: Monotherapy with a selective serotonin reuptake inhibitor (SSRI) is
      the most common initial treatment for major depressive disorder (MDD), but this
      monotherapy leads to remission in fewer than a third of patients. The combination
      of the SSRI escitalopram and bupropion-SR is commonly used for treating patients
      with MDD who have had an inadequate response to antidepressant monotherapy. This
      pilot study was conducted to evaluate this combination in the treatment of MDD in
      patients with chronic or recurrent MDD to estimate safety, tolerability, and
      remission rates. METHOD: In this study, 51 outpatients with chronic or recurrent
      non-psychotic MDD were treated with a combination of escitalopram and bupropion
      SR for up to 12 weeks. Participants were started on escitalopram at 10 mg/day,
      and bupropion-SR was then added at week 1, starting at 150 mg/day. The maximum
      dose of escitalopram was 20 mg/day and the maximum dose of bupropion-SR was 400
      mg/day. RESULTS: Rates of response (62%) and remission (50%) at study exit (based
      on participants for whom at least one post-baseline measure was collected) were
      significantly higher than is typical for SSRI monotherapy. The level of treatment
      emergent adverse events was low, and only 3 participants (6%) discontinued
      treatment due to side effects. The mean maximum dose of escitalopram was 18
      mg/day, which was achieved by week 6, and the mean dose at study exit was also 18
      mg/day. The mean maximum dose of bupropion-SR was 329 mg/day, which was achieved
      by week 8, and the mean dose at study exit was 327 mg/day. CONCLUSIONS: These
      results suggest that the combination of escitalopram and bupropion-SR is
      effective and well tolerated. Further controlled trials comparing this
      combination with monotherapy are needed.

PMID- 18832959
TI  - Effectiveness and efficiency of cognitive-behavioral group therapy for
      inpatients: 4-year follow-up study.
AB  - OBJECTIVES: The goals of this study were to evaluate the effectiveness of
      manualized cognitive-behavioral group therapy (CBGT) integrated into routine care
      on a psychiatric inpatient unit and to compare the impact of the intervention on
      patients with the following diagnoses: schizophrenia, major depression, bipolar
      disorder, or personality disorders. The results presented here expand on those
      presented in a previous publication by including 2 more years of data and
      additional analyses concerning diagnosis and economic outcomes. METHOD: A pre
      post design was used to measure voluntary and compulsory readmissions, ward
      atmosphere, patient satisfaction, mean length of stay, and cost-income in the
      year before CBGT was introduced (2001) compared with the next 4 years. RESULTS:
      In the years 2001-2005, percentage of total readmissions declined from 38% to 24%
      (p < 0.02); of those readmissions, 17% were compulsory in 2001 compared with 0 in
      2005 (p < 0.02). A progressive improvement in ward atmosphere was observed from
      baseline to the following 4 years (p < 0.001). There was also statistically
      significant improvement in patient satisfaction compared with baseline, mainly
      observed during the first 2 years of the intervention (p < 0.001). The reduction
      in readmissions was statistically significant only for patients with
      schizophrenia (p < 0.001) and bipolar disorder (p < 0.04). CONCLUSIONS: These
      results are promising and indicate that CBGT may contribute added benefit to
      treatment on an inpatient psychiatric ward.

PMID- 18832960
TI  - A review of second-generation antipsychotic discontinuation in first-episode
      psychosis.
AB  - "All-causes discontinuation" refers to discontinuation of treatment for any
      reason, and adherence to medication is an important component of this measure.
      Two recent landmark studies suggest that adherence is a major issue in patients
      with first-episode psychosis (FEP) right from the onset of treatment. In this
      review, the incidence, reasons for, and clinical outcomes of medication
      discontinuation in FEP are considered. More than 40% of patients with FEP
      discontinue medication during the first 9 months of treatment, at which point the
      chances of relapse increase dramatically. Findings concerning predictors of
      medication discontinuation in this patient population that have been replicated
      in more than one study include severity of psychopathology, lack of insight into
      illness, negative attitudes towards medications, comorbid substance use, and
      medication side effects. Interventions that have the potential to decrease
      discontinuation rates in patients with psychotic disorders include orally
      disintegrating tablets, long-acting injectable drugs, cognitive-behavioral
      therapy, compliance therapy, family support/intervention, and peer support,
      although these strategies have largely been unexplored in FEP. In addition to the
      question of medication discontinuation in the acute treatment of FEP, another
      important issue is how long patients with FEP should be treated with
      antipsychotics once they have achieved remission; unfortunately, little evidence
      is available to guide the decision as to whether medication should be
      discontinued or maintenance treatment provided in this situation. Studies are
      therefore needed to identify predictors of patients with remitted FEP who are
      less likely to relapse when medication is discontinued. Taken together, the
      findings presented in this article underscore the importance of addressing issues
      related to medication discontinuation as a means of preventing long-term
      morbidity and enhancing remission and functional recovery in FEP.

PMID- 18832961
TI  - Practical application of therapeutic drug monitoring: a tale of two patients.

PMID- 18832962
TI  - Psychoanalytic contributions to the care of medically fragile children.

PMID- 18832963
TI  - Comorbid Diogenes and Capgras syndromes.

PMID- 18832964
TI  - Review of two years of experiences with SPECT among psychiatric patients in a
      rural hospital setting.
AB  - We summarize single proton emission computed tomography (SPECT) findings from 63
      psychiatric patients in a small rural hospital in western Minnesota. SPECT scans
      were ordered only for patients in whom documentation of hypoperfusion and
      functional deficits might be helpful in clarifying diagnoses and treatment
      planning. The patients referred for SPECT scans had histories of traumatic brain
      injuries, atypical psychiatric symptom presentations, or conditions that were
      refractory to standard treatments. In the context of strict referral guidelines
      and close psychiatrist-radiologist collaboration, a much higher yield of
      significant findings was obtained compared with those noted in other reports in
      the literature.

PMID- 18832966
TI  - Robert Mandell: a pioneer and giant in the art and science of contact lenses.
AB  - Robert B. Mandell is the quintessential modern clinical scientist. Over his long
      academic career, he has pioneered many advances in contact lens practice, ranging
      from a more complete understanding of corneal shape to the effects of contact
      lenses on corneal health. His classic text, Contact Lens Practice, first
      published in 1965, was reprinted 14 times in four editions up to 1988. Mandell's
      contributions to the advancement of the profession of optometry have always been
      characterized by a genuine concern for the patient and a steadfast belief that
      his research must have relevance to the practice of optometry.

PMID- 18832967
TI  - Clinical tests for successful contact lens wear: relationship and predictive
      potential.
AB  - PURPOSE: Although comfort is important for contact lens wearers, common clinical
      tests can fail to predict patients' symptoms. Lid wiper epitheliopathy (LWE) and
      lid parallel conjunctival folds (LIPCOF) are related to dry eye symptoms in lens
      wearers. This study investigates the predictive value of LWE and LIPCOF as
      objective measures of discomfort, and their relation to the ocular surface in
      soft contact lens wearers. METHODS: Subjects were classified as symptomatic or
      asymptomatic, using the Contact Lens Dry Eye Questionnaire (CLDEQ). Pre-lens tear
      break-up time (PLBUT), limbal and bulbar hyperaemia, corneal staining, LWE and
      LIPCOF were assessed in the right eyes of 61 (23 M, 38 F; mean age 32.1 years;
      range = 18 to 55) experienced contact lens wearers. Differences between groups,
      and relationships between LWE, LIPCOF (nasal, temporal and sum) and objective
      signs were examined using non-parametric analyses. The positive and negative
      predictive values for symptoms of each objective measure were calculated.
      RESULTS: Thirty eight subjects were classified as asymptomatic, 23 symptomatic.
      LWE and LIPCOF severity scores were significantly increased in symptomatic
      patients (U-test, p < 0.03), while no significant differences were found between
      groups for PLBUT, corneal staining or hyperaemia (0.29 < p < 0.88). Significant
      positive correlations were found between LWE and LIPCOF scores (temporal r =
      0.67, p < 0.001; nasal r = 0.39, p < 0.001), and between LWE and hyperaemia
      (bulbar, r = 0.28, p < 0.001; limbal r = 0.36, p < 0.001). Age and gender were
      different in the two groups (p < 0.05). The predictive value of temporal LIPCOF
      was positive = 56.9%, negative = 77.1% with a cutoff value of > or =2
      (PPV/NPV/cutoff value), of nasal LIPCOF 70.7%/75.0%/> or =1, of LIPCOF Sum
      79.8%/86.5%/> or =2, and of LWE 53.1%/81.1%/> or =1. CONCLUSIONS: Contact lens
      wearers with dryness symptoms exhibit significantly more LWE and LIPCOF, but not
      increased corneal staining, bulbar hyperaemia or decreased PLBUT. LWE and LIPCOF
      are significantly correlated: this may reflect their common frictional origin.
      LIPCOF Sum severity scores appear to be most predictive for symptoms.

PMID- 18832968
TI  - Mucins and ocular signs in symptomatic and asymptomatic contact lens wear.
AB  - PURPOSE: Lid wiper epitheliopathy (LWE) and lid parallel conjunctival folds
      (LIPCOF) are related to dry eye symptoms in contact lens wearers. Both clinical
      signs are assumed to be related to mechanical forces during blinking. As the
      mucus layer is a protector of the ocular surface tissue, this study investigates
      whether any alterations of mucins are detectable comparing symptomatic and
      asymptomatic soft contact lens wearers. METHODS: Comfort was evaluated using the
      Contact Lens Dry Eye Questionnaire. Corneal staining, LWE, and LIPCOF were
      assessed in the right eyes of 50 (19 men, 31 women; mean age, 32.1 +/- 11.4
      years) experienced lens wearers. The tear film was sampled using Schirmer strips
      pressed onto the temporal conjunctiva and from harvested contact lenses. Mucins
      were assessed in dot-blots and Western blots after electrophoresis on 1% agarose
      or 4 to 12% NuPAGE Gels. Non-parametric analyses were used to study differences
      between groups and correlations between objective tests, mucins, and symptoms.
      RESULTS: Thirty-one subjects were classified asymptomatic and 19 symptomatic by
      the questionnaire. LWE and LIPCOF were significantly increased in the symptomatic
      group (p < 0.035). MUC5AC reactivity was significantly decreased in symptomatics
      (p = 0.050). MUC4 was correlated to temporal LIPCOF and LWE, (r = -0.47 and 
      0.46; p < 0.01). MUC16 and MUC5AC correlated with corneal staining (0.36 < r <
      0.53; p < 0.04). CONCLUSIONS: Symptomatic contact lens wearers exhibit
      significantly more LWE and LIPCOF, and decreased MUC5AC reactivity. LWE and
      LIPCOF are significantly correlated; this may reflect their common frictional
      origin. Increased friction might follow from insufficient mucins, or an altered
      composition of the resident mucins at the ocular surface. In this study, we show
      that decreased mucin production is associated with the severity of LWE and
      LIPCOF.

PMID- 18832969
TI  - Fluorescein pattern interpretation in keratoconus.
AB  - PURPOSE: The purpose of this study is to assess the effect of disease severity on
      how accurately contact lens fluorescein patterns can be interpreted in
      keratoconus by clinician assessment. METHODS: Two clinicians evaluated
      fluorescein patterns on 111 eyes of 60 patients with mild (<45 D, 14 eyes),
      moderate (45 D to 52 D, 61 eyes,) and severe (>52 D, 36 eyes) keratoconus. The
      masked clinicians were given six contact lenses in random order, the lens that
      just cleared the corneal apex (the first definite apical clearance lens), three
      lenses flatter (in 0.1 mm increments), and two lenses steeper (in 0.1 mm
      increments) than the first definite apical clearance lens. They ranked the lenses
      from flattest to steepest, based on the fluorescein patterns. The percentage of
      lenses correctly ranked was determined using (1) exact match with actual; (2)
      within 0.1 mm of actual; and (3) within 0.2 mm of actual. Accuracy was assessed
      as the sum of the squared differences between the actual base curve value and
      each clinician's ranking. Comparison of the mean percentage correctly ranked and
      accuracy for each keratoconus severity groups was performed using a mixed linear
      model. RESULTS: Neither percentage correctly ranked (using any of the three
      protocols) nor accuracy was found to be related to severity of keratoconus (p >
      0.15 for all comparisons). CONCLUSIONS: Accuracy of ranking contact lenses in
      order of base curve radius based on fluorescein pattern assessment by clinicians
      does not seem to be related to severity of keratoconus. Many factors influence
      interpretation of fluorescein patterns including all components of the system,
      fluorescein, tears, cornea, contact lens, external forces, and technique.

PMID- 18832970
TI  - Visualizing the limits of low vision in detecting natural image features.
AB  - PURPOSE: The purpose of our study was to develop a tool to visualize the
      limitations posed by visual impairments in detecting small and low-contrast
      elements in natural images. This visualization tool incorporates existing models
      of several aspects of visual perception, such as the band-limited contrast model
      of Peli (J Opt Soc Am A 1996;13:1131-8). METHODS: The models underlying the
      visualization tool were elaborated and tested in experiments with human subjects
      with various visual impairments such as macular degeneration, diabetic
      retinopathy, glaucoma and subjects with normal vision but under various degraded
      viewing conditions (including reduced contrast, eccentric viewing). The
      experiments were designed to determine in three successive steps the contrast
      sensitivity function that produces a degraded image that can just be
      discriminated from its original. In the first step, the just detectable blur was
      determined, while in the next two steps contrast threshold levels were determined
      for removing high and medium spatial frequencies from the image. Threshold
      parameters were determined for three image-types (face, stairs, forest) and the
      relationship with acuity and contrast thresholds (of Landolt-C symbols) was
      examined. RESULTS: The blur threshold is inversely related to acuity, and this
      relationship is largely independent of the cause of reduced acuity (visual
      impairment, contrast reduction or eccentric viewing). CONCLUSIONS: We developed a
      validated visualization tool based on these results that provides a reliable
      impression of detectability of image features by visual impaired people.

PMID- 18832971
TI  - Thickness mapping of the cornea and epithelium using optical coherence
      tomography.
AB  - PURPOSE: To measure corneal and epithelial thickness across four meridians using
      Optical Coherence Tomography (OCT) and to compare these measurements between
      normal non-lens wearers (NLW), rigid gas permeable (RGP) lens wearers, and RGP
      wearing keratoconics (KC). METHODS: Both eyes of 60 subjects were measured (20
      NLW, nine female:11 male, 27.6 +/- 5.9 years; 20 RGP, 20 female, 23.9 +/- 7.6
      years; and 20 KC, seven female:13 male, 32.4 +/- 8.1 years). A customized
      fixation target employing LEDs in eight directions of gaze was attached to the
      OCT and corneal images obtained. Raw OCT scans were analyzed to yield values for
      corneal and epithelial thickness and color-coded maps were compiled. RESULTS:
      Central corneal thickness (CCT) was thinnest in KC (447 +/- 68 microm) and
      similar between RGP (518 +/- 32 microm; pKC < 0.001) and NLW (517 +/- 21 microm)
      (p(KC) < 0.001 NLW pRGP > 0.05). Peripheral corneal thickness in NLW was thickest
      in the superior temporal and thinnest in the inferior (I) regions (superior
      temporal(thickest) vs. I(thinnest) p < 0.001). Central epithelial thickness was
      thinnest in KC (44 +/- 7 microm), followed by RGP (50 +/- 4 microm), then NLW (54
      +/- 2 microm) (pKC < 0.001 NLW p(RGP) < 0.05). Central epithelial thickness in
      the KC group was significantly thinner than in the RGP group (p < 0.001). In the
      NLW group, peripheral epithelial thickness was thicker (63 +/- 5 microm) than
      central (p < 0.001) and was thickest in the superior (S) region and thinnest in
      the inferior (I) region (S(thickest) vs. I(thinnest) p < 0.001). KC epithelium
      was thinnest in the inferior temporal meridian (42 +/- 5 microm). CONCLUSIONS:
      Thickness of the normal cornea and epithelium was greatest in the superior
      region. In all groups, the inferior cornea and epithelium was thinnest, and to a
      greater extent in the KC group.

PMID- 18832972
TI  - Binocular vision changes in university students: a 3-year longitudinal study.
AB  - PURPOSE: The aim of this study was to investigate the changes in accommodation
      and binocular vision parameters during a period of 3 years and to evaluate their
      potential influence on the refractive changes observed over the same period of
      time in a population of university students in Portugal. METHODS: A 3-year
      longitudinal study was conducted comprising 118 young adults (34 males and 84
      females; mean age: 20.6 +/- 2.3 years). Examinations consisted of subjective
      refraction, dissociated phoria and vergences at distance and near vision,
      accommodative convergence/accommodative ratio, lag of accommodation, and the
      negative and positive relative accommodation. RESULTS: There were statistically
      significant differences between the first (2002) and the second examination
      (2005) relative to distance and near phoria, and break and recovery points for
      the base-in and base-out at distance vision. Statistically significant
      differences were also obtained for the blur and break points for the base-out,
      and for break and recovery points for the base-in at near vision. As regards
      accommodation parameters, we verified a statistically significant difference for
      all parameters measured. Comparing the baseline values of patients who suffered a
      myopic shift > or =0.50 D with those from patients who did not experience such a
      shift, we observed a statistically significant difference for the break value of
      the base-in at distance vision (equal to 12.2 +/- 3.6 for the group without
      refractive error alteration and 15.8 +/- 6.8 for the other group) and for the
      break value of the base-in at near vision (equal to 22.4 +/- 5.2 and 24.8 +/- 5.5
      for the group without refractive error alteration and for the other group,
      respectively). CONCLUSIONS: We observed significant changes in near heterophoria,
      fusional vergences, and positive relative accommodation. The break values of the
      base-in fusional vergence account as significant predictors of myopic shift in
      young adults.

PMID- 18832974
TI  - Occupational psychophysics to establish vision requirements.
AB  - PURPOSE: To develop and implement a comprehensive procedure for determining
      vision requirements for different vocational and occupational tasks. METHODS:
      Evaluations performed for more than 10 state agencies and businesses were
      conducted over a period of approximately 9 years. The procedure included a
      literature review, an assessment of potential visual functions to address, a
      formal job analysis, interviews with incumbent workers, obtaining advice and
      recommendations from subject matter experts (experienced incumbents and
      administrators), development of job-related simulation studies, linkage of
      simulation results to the job analysis, a review of appeals and critical
      incidents, a thorough assessment of work environments and conditions, and final
      recommendations. RESULTS: Examples of occupational simulations for quantitative
      job-related task performance for best-corrected visual acuity, uncorrected visual
      acuity, color vision, peripheral vision, the use of one vs. two eyes, naive vs.
      experienced incumbents, and impoverished visual conditions are presented. Changes
      in task performance and confidence ratings were obtained for various levels of
      degraded vision. DISCUSSION: This procedure, referred to as "occupational
      psychophysics," provides a quantitative systematic method of defining the vision
      requirements for various essential job functions. In conjunction with the
      frequency of performance, requirements at entry to the job, safety, reasonable
      accommodation, alteration of the work environment, and administrative issues,
      this approach provides a quantitative, rational basis for establishing job
      related vision requirements.

PMID- 18832975
TI  - Anti-inflammatory drug use and age-related macular degeneration.
AB  - PURPOSE: Basic research has shown that early processes in the development of age
      related macular degeneration (ARMD) are related to inflammation. The purpose of
      this manuscript is to evaluate the association of ARMD and the use of anti
      inflammatory medications. METHODS: A nested case control study was carried out
      among male patients at the Veteran's Medical Center in Birmingham, Alabama
      (BVAMC). Cases were 614 patients with incident ARMD diagnosed between 1997 and
      2001 by International Classification of Disease, Ninth Revision code. Controls
      (4526) were individuals with no diagnosis of ARMD by International Classification
      of Disease, Ninth Revision coding and matched on age. Formulary records of all
      medications dispensed through the Veteran's Administration Medical Center were
      accessed. All oral or injectable drugs with anti-inflammatory properties were
      considered anti-inflammatory medications for study purposes. Topical ophthalmic
      and dermatologic preparations were not considered anti-inflammatory. RESULTS:
      Among veterans with a diagnosis of ARMD 24% (150/614) patients had filled a
      prescription for any of the anti-inflammatory medications compared with 60%
      (3051/4526) individuals in the control population. Individuals who had filled a
      prescription for anti-inflammatory drugs had an 85% reduced odds of having a
      diagnosis of ARMD (odds ratio 0.15, 95% confidence interval 0.12-0.18).
      CONCLUSIONS: The results of this study suggest that veterans who had filled a
      prescription for anti-inflammatory medications had a reduced risk of ARMD.
      Further studies are needed to confirm this result.

PMID- 18832976
TI  - Regional variation in the refractive-index of the bovine and human cornea.
AB  - PURPOSE: Given the refractive importance of the human cornea, surprisingly little
      attention has been directed to the study of local variation in corneal refractive
      index. This in vitro and in vivo study measures the refractive-index of different
      portions of the bovine and human cornea. METHODS: Fifty fresh bovine corneas
      (obtained from an abattoir) and 10 human subjects were used for the study. The
      refractive-index of the central, nasal, and temporal corneal epithelium was
      measured with a bench-top Abbe refractometer in the case of bovine corneas and
      with a hand-held refractometer with humans. RESULTS: The mean (+/-standard
      deviation) refractive-indices of the central, nasal, and temporal bovine corneal
      epithelium were 1.3760 (+/-0.003), 1.3757 (+/-0.002), and 1.3746 (+/-0.002),
      respectively. Refractive-indices of the anterior and posterior bovine corneal
      stroma were 1.3731 (+/-0.002) and 1.3708 (+/-0.004), respectively. The mean (+/
      standard deviation) refractive-index in the central, nasal, and temporal
      periphery of the human cornea epithelium were 1.3970 (+/-0.001), 1.3946 (+/
      0.001), and 1.3940 (+/-0.001), respectively. CONCLUSION: There are small local
      differences in the refractive-index of the bovine and human corneal epithelium
      and the refractive-index of the epithelium is higher than that of the anterior
      and posterior stroma of the bovine cornea.

PMID- 18832977
TI  - Dynamic accommodation responses following adaptation to defocus.
AB  - PURPOSE: Adaptation to defocus is known to influence the subjective sensitivity
      to blur in both emmetropes and myopes. Blur is a major contributing factor in the
      closed-loop dynamic accommodation response. Previous investigations have examined
      the magnitude of the accommodation response following blur adaptation. We have
      investigated whether a period of blur adaptation influences the dynamic
      accommodation response to step and sinusoidal changes in target vergence. METHOD:
      Eighteen subjects (six emmetropes, six early onset myopes, and six late onset
      myopes) underwent 30 min of adaptation to 0.00 D (control), +1.00 D or +3.00 D
      myopic defocus. Following this adaptation period, accommodation responses to a
      2.00 D step change and 2.00 D sinusoidal change (0.2 Hz) in target vergence were
      recorded continuously using an autorefractor. RESULTS: Adaptation to defocus
      failed to influence accommodation latency times, but did influence response times
      to a step change in target vergence. Adaptation to both +1.00 and +3.00 D induced
      significant increases in response times (p = 0.002 and p = 0.012, respectively)
      and adaptation to +3.00 D increased the change in accommodation response
      magnitude (p = 0.014) for a 2.00 D step change in demand. Blur adaptation also
      significantly increased the peak-to-peak phase lag for accommodation responses to
      a sinusoidally oscillating target, although failed to influence the accommodation
      gain. These changes in accommodative response were equivalent across all
      refractive groups. CONCLUSION: Adaptation to a degraded stimulus causes an
      increased level of accommodation for dynamic targets moving towards an observer
      and increases response times and phase lags. It is suggested that the contrast
      constancy theory may explain these changes in dynamic behavior.

PMID- 18832978
TI  - Longitudinal study of visual discomfort symptoms in college students.
AB  - PURPOSE: To determine the variation of visual discomfort symptom reporting in a
      group of college students over a 1 year period. METHODS: Subjects were screened
      for visual acuity and uncorrected refractive error before participating in the
      study. A survey of visual discomfort developed by Conlon et al., Vis Cogn
      1999;6:637-666, and the Convergence Insufficiency Symptom Survey (CISS) were
      administered to a group of 23 college students twice with approximately 1 year
      between administrations. All subjects also completed two clinical assessments of
      accommodation and vergence. RESULTS: The mean time between administrations of the
      symptom surveys was 13 months. There was no clinically significant mean
      difference between the first and second administration of both visual discomfort
      surveys. The intraclass correlation coefficient was 0.82 for the Conlon et al.,
      Vis Cogn 1999;6:637-666 survey and 0.85 for the CISS. The 95% limits of agreement
      for the Conlon et al., Vis Cogn 1999;6:637-666 survey was -18.44, 17.92 and for
      the CISS was -14.36, 13.36. The intraclass correlation coefficient values for the
      optometric tests ranged from 0.38 to 0.83. CONCLUSIONS: Visual discomfort
      symptoms were found to be stable in the majority of young college students over a
      1 year period. However, a minority of students showed large variability between
      the two administrations of the surveys.

PMID- 18832979
TI  - Clinical value of the VMI supplemental tests: a modified replication study.
AB  - PURPOSE: To carry out a modified replication of the study performed by Kulp and
      Sortor evaluating the clinical value of the information provided by Beery's
      visual-motor supplemental tests of Visual Perception (VP) and Motor Coordination
      (MC) in normally developed children. The objectives were to (a) estimate the
      correlations among the three tests scores; (b) assess the predictive power of the
      VP and MC scores in explaining the variance in Visual-Motor Integration (VMI)
      scores; and (c) examine whether poor performance on the VMI is related to poor
      performance on VP or MC. METHODS.: A convenience sample of 71 children ages 4 and
      5 years (M = 4.62 +/- 0.43) participated in the study. RESULTS: The supplemental
      tests significantly (F = 9.59; dF = 2; p < or = 0. 001) explained 22% of the
      variance in VMI performance. Only VP was significantly related to VMI (beta =
      0.39; T = 3.49) accounting for the total amount of explained variance. Using the
      study population norms, 11 children (16% of total sample) did poorly on the VMI;
      of those 11, 73% did poorly on the VP, and none did poorly on the MC. None of
      these 11 did poorly on both the VP and MC. Nine percent of total sample who did
      poorly on the VP performed within the norm on the VMI. Thirteen percent who
      performed poorly on the MC performed within the norm on the VMI. Using the VMI
      published norms, 14 children (20% of total sample) who did poorly on the VP
      performed within the norm on the VMI. Forty-eight percent who did poorly on MC
      performed within the norm on the VMI. CONCLUSIONS: Findings supported Kulp and
      Sortor's conclusions that each area should be individually evaluated during
      visual-perceptual assessment of children regardless of performance on the VMI.

PMID- 18832980
TI  - Normal values of hertel exophthalmometry in children, teenagers, and adults from
      Tehran, Iran.
AB  - PURPOSE: The aim of this study was to present normative values of
      exophthalmometry in Iranian children, teenagers, and adults and find the effect
      of age, gender, height, weight, and laterality (right vs. left eye) on normal
      values of protrusion. METHODS: In a population-based epidemiological study,
      ocular protrusion values (mm) were measured in 1063 randomly selected (stratified
      sampling method) normal subjects using the Hertel exophthalmometer. Weight and
      height were measured in all subjects. RESULTS: There were 462 (43.5%) females and
      601 (56.5%) males. The age ranged from 6 to 70 years (mean +/- SD = 20.3 +/-
      10.9). Subjects were divided into three age groups (years); children (range: 6 to
      12, mean: 9.2 +/- 1.6), teenagers (range: 13 to 19, mean: 15 +/- 1.4), and adults
      (range: 20 to 70, mean: 31 +/- 7.9). The mean (+/-SD) absolute ocular protrusion
      value was 14.2 +/- 1.8 in children, 15.2 +/- 1.9 for teenagers, and 14.7 +/- 2.3
      for adults. Right and left eye protrusions were well correlated (r = 0.97, p <
      0.0005 in children and adults and r = 0.95, p < 0.0005 in teenagers). However,
      right eye protrusion was significantly more than on the left side (p < 0.0005).
      Although males had more eye protrusion, the gender difference was not significant
      except for teenagers. Weight and height did not have a significant effect on eye
      protrusion. No individual had more than 2 mm of asymmetry (relative eye
      protrusion). Increasing age had a significant effect on the eye protrusion (r =
      +0.32 for children, r = +0.13 for teenagers, and r = -0.30 for adults; 0.001 < p
      < 0.0005). The ocular protrusion was positively correlated with increasing
      distance between the two lateral orbital rims (base) in all age groups (p <
      0.0005). CONCLUSIONS: Any eye protrusion of more than 17.8 mm for Iranian
      children, 19 mm for Iranian teenagers, and 19.3 mm for Iranian adults and
      relative eye protrusion of more than 2 mm warrants further clinical examination.
      Age and base value had a significant impact on normal eye protrusion values.

PMID- 18832981
TI  - Intraocular pressure spikes in keratectasia, axial myopia, and glaucoma.
AB  - PURPOSE: To review a range of activities associated with intraocular pressure
      (IOP) spikes. To examine the possible significance of IOP spikes in conditions
      such as keratectasia, axial myopia, and glaucoma. METHODS: Hypotheses concerning
      mechanisms for adverse responses to IOP spikes were examined. RESULTS: Apart from
      the possibility that IOP spikes might cause susceptible corneal, posterior
      scleral, or optic nerve head tissue to yield to associated distending forces,
      there is the possibility that these tissues will be also be damaged by increased
      hydrostatic pressure. CONCLUSIONS: In-office tonometry does not indicate the
      degree to which ocular tissues are exposed to IOP spikes. For eyes that are
      exposed to IOP spikes of longer duration, that occur frequently and which result
      in a larger IOP increment, the risk of an adverse response may be greater.
      Changes in ocular tissues because of increased hydrostatic pressure may include
      morphological cellular changes and alterations to enzyme function. Eye rubbing
      may be the most significant mechanism for creating IOP spikes because of the
      large IOP increments that may be involved, as well as the possibility that
      abnormal rubbing can become a chronic habit. As appears to be the case in
      keratoconus, asymmetric exposure to IOP spikes may help to explain some
      asymmetric presentations of post-laser-assisted in situ keratomileusis, glaucoma,
      or myopia. Ideally methods for the objective assessment of patient risk for
      adverse responses to IOP spikes will continue to be developed. A self
      administered questionnaire may help identify patients who are significantly
      exposed to IOP spikes. Family history may indicate an increased risk of diseases
      for which IOP spikes may have significant implications. Patient counseling
      regarding the possibility that IOP spiking activities may contribute to the
      development and/or progression of conditions such as keratectasia, axial myopia,
      and glaucoma may be indicated.

PMID- 18832982
TI  - Celebrating the specialty of orthopaedic nursing.

PMID- 18832983
TI  - Helping parents make good decisions.

PMID- 18832984
TI  - Rapid response team approach to staff satisfaction.
AB  - Rapid response team (RRT) is a patient care concept that has received nationwide
      attention as a resource for hospital staff nurses. Once nurses identify a patient
      who is clinically declining, they call upon the assistance of the RRT member.
      Within an 800-bed acute care hospital, a job satisfaction survey tool was
      developed to ask licensed staff on an orthopaedic unit what type of impact the
      RRT has on their job satisfaction. Survey results revealed that this approach to
      patient care is significantly important in the orthopaedic nurse job satisfaction
      and an effective recruitment and retention tool for nurses in the orthopaedic
      arena.

PMID- 18832986
TI  - Current concepts in the treatment of hallux valgus.
AB  - Hallux valgus is a common disorder of the forefoot that results from medial
      deviation of the first metatarsal and lateral deviation and/or rotation of the
      great toe (hallux) with or without medial soft-tissue enlargement of the first
      metatarsal head (bunion). It is the most common pathologic condition affecting
      the great toe. There is a known predilection of hallux valgus and bunions in the
      female population (female-male ratio =9:1), which is likely due to both
      biomechanics (joint laxity/instability) and shoe wear demands. There are many
      different conservative and surgical treatment options for hallux valgus and
      bunions. The multitude of established procedures and technique modifications in
      the literature underscores the fact that no single approach universally addresses
      this common disorder.

PMID- 18832988
TI  - Interventions to prevent adolescent motor vehicle crashes: a literature review.
AB  - Adolescent injury and death from motor vehicle crashes continues to be a pressing
      public health concern. The adolescent age group present a unique challenge in
      terms of prevention because of their age and thought processes. Over the years,
      many intervention strategies have emerged to target prevention of motor vehicle
      crashes in this age group. Some have been more successful than others. When
      implementing intervention programs for their own communities, nurses must be
      aware of information regarding adolescent injury prevention in the literature.
      Reality-based prevention programs appear to be a promising intervention strategy
      to target motor vehicle crash prevention in adolescents.

PMID- 18832989
TI  - Celiac disease: its implications for orthopaedic nursing.
AB  - Celiac disease (CD), also known as gluten-sensitive enteropathy, is an inherited
      autoimmune disease that can lead to multisystem effects. Left undiagnosed and
      untreated, it has severe orthopaedic implications involving osteoporosis and
      unnecessary treatment of joint pain, which could be avoided. The orthopaedic
      nurse may have thought that CD was primarily an abdominal disorder. We need to be
      aware of the potential practice implications in orthopaedics by understanding the
      disease, its diagnosis, and treatment. Furthermore, orthopaedic nurses can
      contribute to current research by studying the relationships between CD and
      orthopaedic problems.

PMID- 18832992
TI  - Integrated review of health literacy interventions.
AB  - Health literacy involves reading, numeracy, comprehension, and the ability to
      make appropriate decisions about healthcare. The nurse needs to understand the
      impact health literacy has on patient education. Sixteen research articles that
      used an experimental design were reviewed in this integrated review to examine
      the effectiveness of intervention strategies related to health literacy. The
      studies found that the use of low literacy interventions was focused on making
      health education material easier to understand with the expectation that patients
      would be able to better self-manage their disease or condition. Further research
      is needed to evaluate the effectiveness of recommended low health literacy
      strategies, identify best practices, and determine how these practices can be
      used to benefit the widest range of patients. Nurses need to be involved in the
      development of evidenced-based interventions that meet the needs of patients with
      low health literacy in the least threatening manner.

PMID- 18832993
TI  - New medications and medication changes.
AB  - When nurses in orthopaedic settings are educating a patient about the
      medications, they address not just those medications related to the current
      orthopaedic problem, but all medications the patient is using. During these
      education sessions, nurses will often be asked about new medications, changes in
      medications, or medication recalls the patient may have heard about from friends
      or through media sources. One up-to-date resource for drug information that
      nurses can readily access is the U.S. Food and Drug Administration Web site. In
      the following article, selected examples of information available from the Food
      and Drug Administration includes recently approved drugs, new drug combinations,
      new formulations of established drugs, and drug alerts or warnings. Informed
      nurses, able to educate patients with accurate information about all the
      medications they are using, can reduce the potential for harm and decrease
      unnecessary stress and anxiety.

PMID- 18832996
TI  - Utilization of a Glidescope videolaryngoscope for orotracheal intubations in
      different emergency airway management settings.
AB  - OBJECTIVE: To describe the initial experience of a group of emergency department
      (ED) physicians, utilizing a Glidescope videolaryngoscope (GVL) for orotracheal
      intubations in the ED. METHODOLOGY: A 6-month, single center, prospective
      observational study from 19 Feb 2007 to 18 Aug 2007 was conducted on all
      orotracheal intubations, which involved utilization of the original GVL in
      different emergency airway management scenarios. RESULTS: Overall success of GVL
      intubation was 15 out of 21 (71.4%) cases. The GVL was able to provide at least
      Cormack-Lehane grade I or II laryngoscopy views in all cases. All the operators
      highlighted difficulty in angulating and maneuvering the endotracheal tube for
      insertion through the glottis as the primary difficulty encountered. CONCLUSION:
      We found the GVL to be an effective device in our ED's emergency airway control
      repertoire. Its role in the anticipated difficult airway in the ED will need
      further studies.

PMID- 18832997
TI  - Combined anti-CD40 conditioning and well-timed immunization prolongs CD8+ T cell
      accumulation and control of established brain tumors.
AB  - Adoptive cell transfer has been shown to significantly reduce established tumors
      in both experimental models and cancer patients. Owing to the tolerogenic nature
      of cancer, approaches that lead to durable maintenance of functional T cells in
      tumor-bearing hosts are needed to maximize tumor regression. In this study, we
      investigated strategies to augment CD8+ T-cell (T-CD8)-mediated adoptive
      immunotherapy of mice bearing advanced-stage autochthonous brain tumors by
      targeting a weakly immunogenic epitope. We found that immunization enhanced the
      accumulation of adoptively transferred T-CD8 at the tumor site, but that the
      timing of immunization was critical for optimal T cell expansion. A more rapid
      accumulation of T-CD8 was achieved when mice were conditioned with agonist anti
      CD40 antibody before adoptive transfer due to increased T cell activation against
      the endogenous tumor antigen. Both approaches led to an increase in the lifespan
      of SV11 mice due to decreased tumor progression. However, tumor-specific T-CD8
      did not persist long term at the tumor site after administration of either
      regimen. Importantly, the combination of anti-CD40 conditioning followed by
      optimally timed immunization synergistically promoted long-term maintenance of T
      CD8 in the brain and dramatically enhanced survival. A second round of
      combination immunotherapy resulted in a further increase in survival, suggesting
      long-term tumor sensitivity to CD8+ T-cell-based immunotherapy. These results
      demonstrate that even a weak antigen can be effectively targeted for control of
      established tumors using a combined adoptive transfer plus immune modulation
      approach and suggest that similar strategies may translate to clinical practice.

PMID- 18832998
TI  - Immune response of human propagated gammadelta-T-cells to neuroblastoma recommend
      the Vdelta1+ subset for gammadelta-T-cell-based immunotherapy.
AB  - Human peripheral gammadelta-T-cells are able to induce cytolysis of neuroblastoma
      (Nb) tumor cells. Besides innate effector functions against infected cells and
      tumors, gammadelta-T-cells are involved in T-helper 1/T-helper 2 (TH1/TH2)
      differentiation of alphabeta-T-cells. However, as different gammadelta-T-cell
      subsets vary considerably in their functional properties, the aim of the present
      study was to define repertoires of cytokines, chemokines, and angiogenic factors
      of in vitro expanded Vdelta1+ and Vdelta2+ T cells in response to Nb. After short
      term culture, both subsets released TH1 [interleukin (IL)-2, interferon (IFN)
      gamma, IL-12, tumor necrosis factor (TNF)-alpha, TNF-beta)] and TH2 cytokines (IL
      4, -5, -6, -10, -13, Vdelta1 also transforming growth factor (TGF)-beta,
      chemokines (I-309, monocyte chemotactic protein (MCP)-1-3, regulated upon
      activation, normal T-cell expressed and secreted), ILs (IL-1, -8, -15), cytokines
      (leptin) as well as angiogenic growth factors [angiogenin (ANG), vascular
      endothelial growth factor (VEGF), epidermal growth factor (EGF), Insulin-like
      growth factor (IGF)-I]. These molecules were expressed at higher levels in
      Vdelta2+ than Vdelta1+ T cells. Nb challenge changed protein expression. TH2
      cytokine and IFN-gamma release was blocked in both gammadelta-T-cell subsets. In
      Vdelta2 gammadelta-T-cells, TH1 cytokines were down-regulated and tumor growth
      promoting factors (ANG, VEGF, EGF, and IGF-I) were strongly up-regulated. In
      contrast, Vdelta1+ gammadelta-T-cells stopped the release of tumor-supportive
      factors and tolerogenic TGF-beta, and strongly up-regulated TNF-alpha, TNF-beta,
      MCP-1 and -2 and maintained their IL-2 production. In summary, our data show that
      after being challenged with Nb cells, propagated Vdelta1+ rather than Vdelta2+ T
      cells support antitumor responses by secretion of proinflammatory cytokines.
      Furthermore, in contrast to other cell types, Vdelta1+ T cells do not sustain a
      growth-promoting or tolerogenic microenvironment. These data make Vdelta1+ T
      cells an ideal candidate for upcoming immunotherapy trials in Nb.

PMID- 18832999
TI  - Intratumoral dendritic cells and chemoradiation for the treatment of murine
      squamous cell carcinoma.
AB  - Dendritic cells are potent antigen-presenting cells that have been shown to have
      significant antitumor effects in vitro and in vivo. However, the therapeutic
      efficacy of dendritic cells as an immunotherapeutic treatment has been limited by
      both immunologic tolerance and active immunosuppression in the tumor
      microenvironment. To address this problem, we examined the ability of concurrent
      systemic chemotherapy and local, fractionated radiation to augment intratumoral
      dendritic cell injections in a mouse model of squamous cell carcinoma.
      Intratumoral injections of dendritic cells alone did not have a significant
      antitumor effect in mice with squamous cell carcinoma flank tumors, but the
      addition of chemoradiation resulted in significant tumor regression. Concurrent
      chemoradiation alone resulted in slower tumor growth, but no complete tumor
      regressions. The combination of chemoradiation and intratumoral dendritic cell
      injections resulted in improved survival and complete tumor regression in 30%
      mice. Mice with complete tumor regression were partially resistant to the repeat
      challenge with relevant tumor 60 days after treatment. These findings were
      partially dependent on the presence of CD4 T cells, CD8 T cells, and natural
      killer cells. Chemoradiation may augment intratumoral dendritic cell injections
      through increased intratumoral apoptosis and decreased intratumoral regulatory T
      cells. This work suggests a possible role for the use of intratumoral dendritic
      cell therapy with more traditional chemoradiation strategies.

PMID- 18833000
TI  - A novel CD19-directed recombinant bispecific antibody derivative with enhanced
      immune effector functions for human leukemic cells.
AB  - A novel bispecific antibody-derived recombinant protein targeting leukemias and
      lymphomas was designed, a single-chain Fv triple body (sctb) consisting of 1
      polypeptide chain with 3 scFvs connected in tandem. The distal scFvs were
      specific for the tumor antigen CD19, and the central scFv for the trigger
      molecule CD16 (FcgammaRIII) on natural killer (NK) cells and macrophages. We had
      previously built a disulphide stabilized (ds) bsscFv [19 x 16] with monovalent
      binding for CD19 from ds components. The sctb ds[19 x 16 x 19] also used ds
      components and displayed 3-fold greater avidity for CD19 than the bsscFv (KD = 13
      vs. 42 nM), whereas both had equal affinity for CD16 (KD = 58 nM). Plasma half
      lives in mice were 4 and 2 hours for the sctb and the bsscFv, respectively. In
      antibody-dependent cellular cytotoxicity reactions with human mononuclear cells
      as effectors, the sctb promoted equal lysis of leukemic cell lines and primary
      cells from leukemia and lymphoma patients at 10-fold to 40-fold lower
      concentrations than the bsscFv. This new format may also be applicable to a
      variety of other tumor antigens and effector molecules. With half-maximum
      effective concentrations (EC50) in the low picomolar range, the sctb ds[19 x 16 x
      19] is an attractive candidate for further preclinical evaluation.

PMID- 18833001
TI  - Anisomycin inhibits the behaviors of T cells and the allogeneic skin
      transplantation in mice.
AB  - There is still a lack of a high potent and low toxic immunosuppressive drug. We
      accidentally found that a quite low dose of anisomycin was sufficient to block
      proliferation of T cells. In this study, carboxy-fluorescein diacetate
      succinimidyl ester staining showed that over 10.0 ng/mL of anisomycin markedly
      inhibited the proliferation of T cells induced by ConA. Propidium iodide staining
      revealed that anisomycin led to G0/G1 arrest and blocked S phase entry stimulated
      by ConA or phorbol 12, 13-dibutyrate plus ionomycin. Anisomycin down-regulated
      remarkably the CD69 and CD25 expression on the surface of T cells. The response
      of T cells was repressed by treatment of anisomycin, which was partly restored by
      adding exogenous interleukin-2, and there was no difference between anisomycin
      and dexamethasone, although the used dose of the latter was 100-fold of the
      former. The inhibition of cytotoxicity of T cells against 7919 cells by
      anisomycin was observed without the direct cytotoxicity to T cells or 7919 cells.
      The level of transforming growth factor-beta1 fell by <80.0 ng/mL in vitro and
      30.0 mg/kg of anisomycin in vivo and enhanced by more than the doses. The
      treatment of anisomycin prolonged the survival of the transplanted skin and
      depressed the delayed type hypersensitivity development and the T-cell response
      in the skin-transplanted mice. Moreover, the effect of its restraining allograft
      rejection might be superior to cyclosporine A, with relatively slight toxic
      signs. These results indicate anisomycin significantly inhibits the behaviors of
      T cells and the transplantation rejection, providing important evidence for
      anisomycin as a novel immunosuppressant.

PMID- 18833002
TI  - Immune responses detected in urothelial carcinoma patients after vaccination with
      NY-ESO-1 protein plus BCG and GM-CSF.
AB  - Urothelial carcinoma of the bladder is a solid tumor entity for which the
      immunomodulatory agent Bacillus-Calmette Guerin (BCG) has been shown to have
      substantial efficacy with approximately 90% cure rates in select patients with
      superficial disease. Immune-based therapies for patients with more invasive
      disease do not currently exist. We previously showed that invasive urothelial
      carcinomas express the NY-ESO-1 tumor antigen. Here we evaluated the safety and
      immunogenicity of a recombinant NY-ESO-1 protein vaccine, which was administered
      with granulocyte macrophage colony-stimulating factor and BCG as immunologic
      adjuvants in a cohort of urothelial carcinoma patients. Sixty-two urothelial
      carcinoma patients were screened for enrollment onto the vaccine clinical trial
      and 6 patients met all eligibility criteria to receive vaccination. Patients with
      localized disease underwent surgical removal of their bladders as treatment for
      their disease. Tumor tissues were tested for NY-ESO-1 expression and eligible
      patients, shown to have NY-ESO-1 tumors, were vaccinated in the postoperative
      setting. Peripheral blood samples were analyzed for vaccine-induced antibody and
      T-cell responses. The vaccine regimen was well tolerated with only mild injection
      site reactions. NY-ESO-1-specific antibody responses were induced in 5/6 patients
      whereas CD8 T-cell responses occurred in 1/6 patients and CD4 T-cell responses
      were found in 6/6 patients. This study demonstrates safety and feasibility of the
      NY-ESO-1 recombinant protein in combination with BCG and granulocyte macrophage
      colony-stimulating factor to induce predominantly antibody and CD4 T-cell
      responses in urothelial carcinoma patients. Induction of higher frequency of CD8
      T-cell responses may be possible in clinical trials implementing NY-ESO-1
      vaccination in combination with other immunomodulatory agents.

PMID- 18833003
TI  - Tumor antigen-specific T-cells are Present in the CD8alphaalpha+ T-cell effector
      memory pool.
AB  - CD8+ T-cell memory formation has recently been demonstrated to be associated with
      CD8alphaalpha homodimer expression by T-cells in mice. Up to now, the knowledge
      about the clinical significance of CD8alphaalpha+ T-cells in humans is limited.
      We assessed in longitudinally collected blood samples from patients with
      melanoma, who underwent a peptide-based vaccination, the role of CD8alphaalpha+ T
      cells in tumor-specific cellular immune responses. Phenotypic analysis showed
      that the expression of CD8alphaalpha+ by T-cells was stable over time and
      associated with a CD45RA+/-CCR7- effector-memory profile. Melan-A/MART-1-specific
      T-cells were identified in the CD8alphaalpha+ T-cell compartment by tetramer
      technology. Detection of intracellular cytokine production (interleukin-2,
      interferon-gamma, and tumor necrosis factor-alpha) upon phorbol 12-myristate 13
      acetate-ionomycin stimulation in CD8alphaalpha+ and CD8alphabeta+ T-cells
      revealed that CD8alphaalpha+ T-cells show a unique cytokine production pattern
      (tumor necrosis factor-alpha and interferon-gamma production) as compared with
      CD8alphabeta+ T-cells. T-cell receptor-CDR3 length analysis revealed that Melan
      A/MART-1-specific CD8alphaalpha+ T-cells showed a similar T-cell receptor
      repertoire as compared with Melan-A/MART-1-specific CD8alphabeta+ T-cells. Our
      results show that CD8alphaalpha+ T-cells represent a compartment of CD45RA+/-
      effector-memory cells in the peripheral circulation of patients with melanoma and
      suggest that CD8alphaalpha T-cells may originate from CD8+ T-cells that have down
      regulated the expression of the CD8beta chain. CD8alphaalpha+ and tetramer
      specific T-cells may represent a valuable marker to gauge long-term antigen
      specific T-cell memory.

PMID- 18833004
TI  - Clinical-scale lentiviral vector transduction of PBL for TCR gene therapy and
      potential for expression in less-differentiated cells.
AB  - In human gene therapy applications, lentiviral vectors may have advantages over
      gamma-retroviral vectors because of their ability to transduce nondividing cells,
      their resistance to gene silencing, and a lack of integration site preference. In
      this study, we used VSV-G pseudotype third generation lentiviral vectors
      harboring specific antitumor T-cell receptor (TCR) to establish clinical-scale
      lentiviral transduction of peripheral blood lymphocyte (PBL). Spinoculation
      (1000g, 32 degrees C for 2 h) in the presence of protamine sulfate represents the
      most efficient and economical approach to transduce a large number of PBLs
      compared with RetroNectin-based methods. Up to 20 million cells per well of a 6
      well plate were efficiently transduced and underwent an average 50-fold expansion
      in 2 weeks. TCR transduced PBL-mediated specific antitumor activities including
      interferon-gamma release and cell lysis. Compared with gamma-retroviral vectors,
      the TCR transgene could be preferentially expressed on a less-differentiated cell
      population.

PMID- 18833005
TI  - An MVA-based vaccine targeting the oncofetal antigen 5T4 in patients undergoing
      surgical resection of colorectal cancer liver metastases.
AB  - We investigated the use of a therapeutic vaccine, TroVax in patients undergoing
      surgical resection of colorectal cancer liver metastases. Systemic immunity
      generated by vaccination before and after resection of metastases was measured in
      addition to assessing safety and analyzing the function and phenotype of tumor
      associated lymphocytes. Twenty patients were scheduled to receive 2 TroVax
      vaccinations at 2-week intervals preoperatively and 2 postoperatively; if immune
      responses were detected, 2 further vaccinations were offered. Blood was taken at
      trial entry and 2 weeks after each vaccination; tumor biopsies were collected at
      surgery. 5T4-specific cellular responses were assessed by lymphocyte
      proliferation and enzyme-linked immunosorbent spot, with antibody responses by
      enzyme-linked immunosorbent assay. Immunohistochemistry characterized the
      phenotype of tumor-infiltrating lymphocytes. Seventeen of 19 colorectal cancer
      patients showed 5T4 expression in the liver metastases or surrounding stroma and
      18 mounted a 5T4-specific cellular and/or humoral response. In patients who
      received at least 4 vaccinations and potentially curative surgery (n=15), those
      with above median 5T4-specific proliferative responses or T-cell infiltration
      into the resected tumor showed significantly longer survival compared with those
      with below median responses. Seven of 8 patients who had preexisting
      proliferative responses to 5T4 were longer-term survivors; these patients showed
      significantly higher proliferative responses after vaccination than those who
      subsequently died. These data suggest that the magnitude of 5T4 proliferative
      responses and the density of CD3 cells in colorectal cancer liver metastases are
      associated with longer survival. These observations warrant more studies to
      identify the precise underlying mechanisms.

PMID- 18833006
TI  - A phase 1/2 study of autologous neuroblastoma tumor cells genetically modified to
      secrete IL-2 in patients with high-risk neuroblastoma.
AB  - Autologous neuroblastoma (NB) tumor cells modified to secrete interleukin (IL)-2
      (auto-IL-2) can be safely given to patients with advanced neuroblastoma and
      generate antitumor immune responses. As the benefits of tumor immunization may be
      greater in patients with minimal residual disease and thus rely on surrogate
      markers such as immune responses to measure effect, we studied the frequency of
      immune changes associated with vaccination. Thirteen patients (8 in first
      remission and 5 after treatment for recurrent NB) received 5 to 8 subcutaneous
      injections of auto-IL-2 at 0.3 x 10 cells/kg. The vaccine was well tolerated.
      Injection site biopsies revealed increased cellularity caused by infiltration of
      CD4 and CD8 lymphocytes, eosinophils, and dendritic cells. Enzyme-linked
      immunosorbent spot assays for interferon-gamma and IL-5 demonstrated that
      vaccination produced a rise in circulating CD4 and CD8 T cells responsive to
      stimulation by autologous tumor cells. Median event-free survival was 22 months
      for patients in first remission and 3 months for all others. Four patients
      treated in first remission remain alive and 3 without disease recurrence.

PMID- 18833007
TI  - Donor regulatory T cells identified by FoxP3 expression but also by the
      membranous CD4+CD127low/neg phenotype influence graft-versus-tumor effect after
      donor lymphocyte infusion.
AB  - Regulatory T cells (Treg) play a pivotal role in the control of graft-versus-host
      disease (GVHD) and might also influence the graft-versus-tumor effect after
      allogeneic stem cell transplantation. We assessed this role after donor
      lymphocyte infusions (DLIs) by quantifying Treg in DLI products, using the CD25,
      Foxp3 but also the recently identified CD127 Treg markers. Compared with others,
      patients in durable complete remission of their malignancy after DLI had received
      a lower number of FoxP3CD25, FoxP3CD127, or CD4CD127 Treg cells (P=0.04). The
      CD4CD127 Treg content of DLI remained significantly correlated with the
      hematologic response in multivariate analysis (P=0.05). Treg may thus inhibit
      graft-versus-tumor effect after DLI, a setting where the antitumoral effect
      observed is only driven by T-cell-mediated cytotoxicity, independently of any
      other associated treatment. In comparison with the intracytoplasmic Foxp3 marker,
      the membranous CD4CD127 phenotype of Treg could be particularly relevant to
      manipulate this cell-population, to increase the antitumoral response in
      strategies of allogeneic or autologous immunotherapy.

PMID- 18833008
TI  - Dendritic cells: a critical player in cancer therapy?
AB  - Cancer immunotherapy seeks to mobilize a patient's immune system for therapeutic
      benefit. It can be passive, that is, transfer of immune effector cells (T cells)
      or proteins (antibodies), or active, that is, vaccination. Early clinical trials
      testing vaccination with ex vivo generated dendritic cells (DCs) pulsed with
      tumor antigens provide a proof-of-principle that therapeutic immunity can be
      elicited. Yet, the clinical benefit measured by regression of established tumors
      in patients with stage IV cancer has been observed in a fraction of patients
      only. The next generation of DC vaccines is expected to generate large numbers of
      high avidity effector CD8 T cells and to overcome regulatory T cells and
      suppressive environment established by tumors, a major obstacle in metastatic
      disease. Therapeutic vaccination protocols will combine improved DC vaccines with
      chemotherapy to exploit immunogenic chemotherapy regimens. We foresee adjuvant
      vaccination in patients with resected tumors but at high risk of relapse to be
      based on in vivo targeting of DCs with fusion proteins containing anti-DCs
      antibodies, antigens from tumor stem/propagating cells, and DC activators.

PMID- 18833010
TI  - Role of pneumococcal proteins in sensorineural hearing loss due to otitis media.
AB  - HYPOTHESIS: Two Streptococcus pneumoniae proteins, pneumococcal surface protein A
      (PspA) and pneumolysin (Ply), have functional and histopathologic effects on the
      inner ear. BACKGROUND: Temporary or permanent sensorineural hearing loss is known
      to be a sequela of pneumococcal otitis media. Several pneumococcal proteins such
      as PspA and Ply have been shown to contribute to the pathogenesis of the middle
      ear; however, effects of these proteins on the inner ear and hearing loss are
      unknown. METHODS: Middle ears of chinchillas were inoculated with either wild
      type S. pneumoniae or its mutants, deficient in PspA or Ply proteins. After 28
      days, auditory brainstem response of animals was tested, and their bullae were
      processed for histopathologic analysis by light microscopy. RESULTS: Twenty-eight
      days after instillation of 20 colony-forming units of wild-type pneumococci,
      auditory brainstem response test showed threshold changes of 10 to 15 dB for 4 to
      32 kHz and more than 20 dB for 1 to 2 kHz. No significant hearing loss was
      observed after instillation of the same or even higher doses of isogenic S.
      pneumoniae mutants of PspA or Ply proteins, or saline injection, after the same
      period. Histologic analysis showed no fluid, inflammatory cells, or bacteria in
      the middle ear, indicating that hearing loss was sensorineural. Inner ear
      morphology showed pathologic changes in the stria vascularis, suggesting it as
      the target of otitis media-induced damage, which may lead to sensorineural
      hearing loss. CONCLUSION: The virulence PspA and Ply proteins of S. pneumoniae
      affect the inner ear and auditory function.

PMID- 18833009
TI  - Neuroimaging studies of normal brain development and their relevance for
      understanding childhood neuropsychiatric disorders.
AB  - OBJECTIVE: To review the maturational events that occur during prenatal and
      postnatal brain development and to present neuroimaging findings from studies of
      healthy individuals that identify the trajectories of normal brain development.
      METHOD: Histological and postmortem findings of early brain development are
      presented, followed by a discussion of anatomical, diffusion tensor, proton
      spectroscopy, and functional imaging findings from studies of healthy
      individuals, with special emphasis on longitudinal data. RESULTS: Early brain
      development occurs through a sequence of major events, beginning with the
      formation of the neural tube and ending with myelination. Brain development at a
      macroscopic level typically proceeds first in sensorimotor areas, spreading
      subsequently and progressively into dorsal and parietal, superior temporal, and
      dorsolateral prefrontal cortices throughout later childhood and adolescence.
      These patterns of anatomical development parallel increasing activity in frontal
      cortices that subserves the development of higher-order cognitive functions
      during late childhood and adolescence. Disturbances in these developmental
      patterns seem to be involved centrally in the pathogenesis of various childhood
      psychiatric disorders including childhood-onset schizophrenia, attention
      deficit/hyperactivity disorder, developmental dyslexia, Tourette's syndrome, and
      bipolar disorder. CONCLUSIONS: Advances in imaging techniques have enhanced our
      understanding of normal developmental trajectories in the brain, which may
      improve insight into the abnormal patterns of development in various childhood
      psychiatric disorders.

PMID- 18833012
TI  - Earnest references in otology.

PMID- 18833013
TI  - Successes and complications of the Baha system.
AB  - OBJECTIVE: To determine the incidence and type of complications, as well as
      patient satisfaction, associated with the Baha system. STUDY DESIGN:
      Retrospective case review. SETTING: The Silverstein Institute, Sarasota, Florida,
      and the Columbia University Medical Center, New York, New York. PATIENTS:
      Patients with conductive/mixed hearing loss and single-sided deafness implanted
      with the Baha system between June 1998 and December 2007. INTERVENTION:
      Implantation with the Baha system. MAIN OUTCOME MEASURE: Incidence and type of
      complications associated with Baha implantation and patient satisfaction as
      measured by a questionnaire administered on site or by telephone. RESULTS: : In
      our series of 218 patients (223 ears), there were no major complications. Of
      these patients, 4.5% required revision surgery for soft tissue complications and
      1.3% needed revision for failure of osseointegration. Eight percent (8%) required
      local care and resolved within 2 to 3 weeks of treatment. Five percent (5%)
      required in office procedures. One hundred six (106) patients satisfactorily
      completed the survey questionnaire. Ninety-two percent (92%) reported using the
      device regularly and 77% were happy with the device. On average, patients
      reported using the device 10.1 h/d, 5.6 d/wk. CONCLUSION: The Baha system is safe
      and effective in the rehabilitation of patients with conductive or mixed hearing
      losses and with single-sided deafness. The high success rate, patient
      satisfaction rate, and predictable auditory outcome place the Baha among the
      leading choices for auditory rehabilitation.

PMID- 18833014
TI  - Postural control at 7 years of age after preterm birth with very low birth
      weight.
AB  - OBJECTIVES: To measure postural control in extremely preterm infants with a birth
      weight of less than 1,500 g in comparison to full-term infants at 7 years of age
      and healthy adults. PATIENTS AND MAIN OUTCOME MEASURES: On a Balance Master
      computerized force plate, static and dynamic postural control was measured in 21
      full-term 7-year-old children, 44 extremely preterm 7-year-old children, and 19
      healthy adults. The test battery consisted of the modified clinical test of
      sensory interaction on balance, the rhythmic weight shift, the walk across, and
      the tandem walk tests. INTERVENTION: Diagnostic, prospective, single-center
      cohort study. RESULTS: Static and dynamic postural control was significantly
      better in adults than in children at 7 years of age. In most parameters, static
      and dynamic postural control was not significantly different between full-term
      and preterm infants with very low birth weight at 7 years of age. Only the ratio
      of intended to extraneous movement, that is, the left-right directional control,
      was significantly lower during the left-right rhythmic weight shift for almost
      all parameters in the study group of preterm infants. CONCLUSION: Postural
      control still is not fully developed in infants at early school age. At this age,
      formerly extremely preterm infants without major neurological disorders have
      almost caught up to the postural control of healthy full-term subjects.

PMID- 18833015
TI  - Subjective visual vertical during eccentric rotation in patients with benign
      paroxysmal positional vertigo.
AB  - OBJECTIVE: There have been only a few reports of subjective visual vertical (SVV)
      in patients with benign paroxysmal positional vertigo (BPPV), and each showed
      slightly different results. SVV measurement during eccentric rotation that
      stimulated only 1 labyrinth was known to show a considerable improvement in
      comparison with conventional SVV as a clinical measure of otolith function. But
      there has not been a report regarding SVV during eccentric rotation in patients
      with BPPV. We therefore measured SVV during eccentric rotation and investigated
      the function of utricles in patients with BPPV. STUDY DESIGN: Retrospective
      study. SETTING: Tertiary referral center. PATIENTS: Twenty-three patients with
      BPPV. INTERVENTION: Diagnostic procedure. MAIN OUTCOME MEASURES: SVV was measured
      in 23 patients with BPPV and 20 normal subjects. We compared the SVV values
      before and during eccentric rotation toward the right and left in both patients
      with BPPV and the control group. RESULTS: Between BPPV patients and the control
      group, no difference in the SVV value was observed in pre-eccentric rotation, but
      significant differences of SVV values were found during eccentric rotation.
      CONCLUSION: We identified utricular dysfunction in patients with BPPV during
      eccentric rotation and suggested that eccentric rotation might be a good method
      to measure utricular dysfunction.

PMID- 18833016
TI  - Generalized arteriosclerosis and changes of the cochlea in young adults.
AB  - HYPOTHESIS: To disclose the histopathologic findings of the cochlea in young
      adults with generalized arteriosclerosis. BACKGROUND: It is well known that
      arteriosclerosis begins and progresses during childhood. Although the
      relationship between arteriosclerosis and auditory function in elderly people was
      examined in many reports, the histopathologic effect of arteriosclerosis on the
      cochlea in young adults has not been studied. METHODS: This study involved
      quantitative analysis, including the number of spiral ganglion cells, the loss of
      cochlear outer hair cells, and the areas of stria vascularis and spiral ligament.
      It included 10 temporal bones from 6 subjects with generalized arteriosclerosis
      and 10 age-matched normal control temporal bones from 7 subjects. RESULTS: The
      mean number of spiral ganglion cells in the cochlea with generalized
      arteriosclerosis was significantly lower than that in normal controls in the
      basal turn. The mean loss of outer hair cells in the cochlea with generalized
      arteriosclerosis was significantly greater than that of normal controls in the
      basal and apical turns. The stria vascularis and spiral ligament were severely
      atrophic, with generalized arteriosclerosis in the basal turn. There was no
      significant difference in the thickness of the spiral modiolar artery between
      generalized arteriosclerosis and normal controls. CONCLUSION: Degeneration of the
      cochlea, especially in the basal turn, was already apparent in young adults with
      generalized arteriosclerosis.

PMID- 18833017
TI  - Variational anatomy of the human cochlea: implications for cochlear implantation.
AB  - HYPOTHESIS: To study variations in human cochlea anatomy with potential
      implications for cochlear implantation surgery. BACKGROUND: A comprehension of
      the anatomic variations of the human cochlea is essential for understanding the
      degree of surgical trauma induced by inserting various electrode arrays in
      cochlear implantation surgery. Variations in anatomy may also limit the potential
      for performing hearing preservation. METHODS: We studied 73 archival,
      nonselected, adult, corrosion casts of human inner ears. Anatomic reference
      points were constructed from photographic reproductions taken at different
      angles, and various dimensions were assessed using planimetry. Anatomic variants
      with particular clinical/surgical interests were pinpointed. RESULTS: Results
      showed that the human cochlea is individually shaped, varying greatly in
      dimensions ("fingerprint"). The outer cochlear wall length ranged from 38.6 to
      45.6 mm with a mean length of 42.0 mm. The first turn represented 53% of the
      total length and ranged from 20.3 to 24.3 mm. The number of quadrants varied from
      slightly more than 8 to 12. The facial nerve canal ran in close proximity to the
      upper first turn explaining facial nerve excitement during stimulation of
      electrodes in this region in some instances. The internal diameter (height) of
      the cochlear tube in the first turn varied broadly (1.6-2.6 mm), occasionally
      with limited space for conventional implants. CONCLUSION: The human cochlea
      exhibits extensive anatomic variations. These variations will influence the
      location of cochlear implant arrays and affect the potential of hearing
      preservation surgery. Our results may explain the surgeon's difficulties
      sometimes to insert electrode arrays even in so-called "normal" cochleae.

PMID- 18833018
TI  - The effects of cochlear implant electrode deactivation on speech perception and
      in predicting device failure.
AB  - OBJECTIVE: To examine speech perception outcomes as related to a reduction in the
      number of functional electrodes postimplantation and to determine the effect of
      electrode reduction on subsequent device failure. STUDY DESIGN: Retrospective
      review. SETTING: Tertiary academic referral center. PATIENTS: Of 1,520 children
      and adults with full insertions of the Advanced Bionics, Med El, and Nucleus
      devices, 15 (1%) were patients. Patients were included in the study if all
      electrodes were functional at initial stimulation, but the number of electrodes
      in use was subsequently reduced at follow-up programming sessions. Exclusion
      criteria included partial and split-array electrode insertions. INTERVENTION(S):
      Patients with bilateral severe to profound sensorineural hearing loss underwent
      either unilateral or bilateral cochlear implantation. MAIN OUTCOME MEASURE(S):
      Postimplantation speech perception tests obtained with a full complement of
      functional electrodes were performed and the results compared to those obtained
      with 1 or more electrodes removed from the user program. Electrode deactivation
      was also correlated with device failure. RESULTS AND CONCLUSION: The results of
      this study indicate that deactivation of cochlear implant electrodes is
      relatively uncommon, and although the deactivation does not have a direct
      influence on speech performance outcomes, the loss of 5 or more electrodes can
      suggest impending device failure. Additionally, those patients with electrode
      deactivation coupled with a decline in speech perception scores should also be
      considered at risk for device failure.

PMID- 18833019
TI  - Electromyographical recording of the electrically elicited stapedius reflex via a
      bipolar hook electrode.
AB  - OBJECTIVE: To prove the feasibility of recording stapedius reflexes by bipolar
      electromyography intra-operatively during cochlea implant via a bipolar hook
      needle electrode. STUDY DESIGN: Prospective study. SETTING: Tertiary referral
      center. PATIENTS: Adults receiving a MED-EL cochlear implant. INTERVENTION:
      Diagnostic. MAIN OUTCOME MEASURES: Stapedius reflex responses can be recorded by
      electromyography. RESULTS: A double hook electrode could be inserted into the
      muscle tissue via the natural opening of the pyramid process along with the
      stapedius tendon. In 7 out of 10 patients supplied with MED-EL CIs (PULSARCI100
      or SONATATI100), electrically elicited stapedius reflex potentials were recorded
      after eliminating stimulation artifacts caused by electromagnetic fields during
      electrical stimulation by low pass filtering. CONCLUSION: Intraoperative
      stapedius reflex recording by bipolar electromyography via a hook electrode is
      feasible. Further research will show whether these signals may be used for
      establishing a self-adjusting speech processor.

PMID- 18833020
TI  - Clinical significance of vestibular evoked myogenic potentials in benign
      paroxysmal positional vertigo.
AB  - OBJECTIVE: To investigate the vestibular evoked myogenic potentials (VEMPs)
      resulting in benign paroxysmal positional vertigo (BPPV) patients and to verify
      its clinical applications in BPPV. STUDY DESIGN: A prospective study. SETTING:
      Tertiary referral dizziness center. PATIENTS: Forty-one patients with diagnosis
      of BPPV and 92 healthy volunteers who underwent VEMP testing. INTERVENTION:
      Patients were treated by canalith repositioning maneuvers according to the
      affected canal, and testing of VEMP was performed at diagnosis and after
      treatment. MAIN OUTCOME MEASURES: Testing of VEMP was performed in BPPV patients
      and in the control group. The number of times the canalith repositioning maneuver
      was repeated until the patient's report of relief from vertigo and findings of
      negative positioning test were recorded to find out the relationship between VEMP
      results and the progress of disease. RESULTS: Vestibular evoked myogenic
      potential results of BPPV patients showed prolonged p13 and n23 latencies
      compared with those of the control group, and we could not find any significant
      difference in VEMP latencies between patients with posterior and horizontal canal
      type of BPPV. The number of times that the maneuver was repeated did not
      correlate with the degree of latency prolongation, but in the "no response"
      group, the number of times was considerably greater than that in the "response"
      group. CONCLUSION: We found that VEMP latencies are increased in BPPV patients,
      which may signify neuronal degenerative changes in the macula of the saccule.
      When an extensive neuronal damage was suspected by VEMP results such as "no
      response" in VEMP, the disease progress showed a chronic and resistive course.
      Therefore, we propose that VEMP could be a useful method to determine a clinical
      prognosis of patients with BPPV.

PMID- 18833021
TI  - Benign paroxysmal positional vertigo and clinical test of sensory interaction and
      balance in systemic sclerosis.
AB  - OBJECTIVE: To assess the frequency and characteristics of benign paroxysmal
      positional vertigo (BPPV) and clinical test of sensory interaction and balance
      (CTSIB) abnormalities in patients with systemic sclerosis (SSc). STUDY DESIGN: A
      series of consecutive patients diagnosed with SSc according to well-established
      classification criteria and matched controls were studied. SETTING: The study was
      performed at the otolaryngology division of a tertiary reference center.
      PATIENTS: Forty-two patients (35 with limited SSc [lSSc] and 7 with diffuse SSc
      [dSSc]) and 74 controls were studied between January and May 2007. INTERVENTION:
      Dix-Hallpike and cephalic rotational tests and CTSIB were performed in SSc
      patients and age-, sex-, and ethnically frequency-matched controls. MAIN OUTCOME
      MEASURE: Type and frequency of BPPV and CTSIB conditions were assessed. RESULTS:
      Seven patients (17%) fulfilled the diagnostic criteria for BPPV compared with
      none of the controls (p < 0.001). It was related to the involvement of the
      posterior semicircular canal in two lSSc patients and the horizontal semicircular
      canal in another three patients with lSSc and two with dSSc. A significantly
      increased frequency of abnormal CTSIB was also observed in SSc patients (20
      [48%]) compared to controls (7 [10%]; p < 0.0001; odds ratio, 8.70; 95%
      confidence interval, 2.97-27.2). It was caused by a vestibular pattern in most
      patients (p < 0.0001). CONCLUSION: The present study shows an increased frequency
      of BPPV and a vestibular pattern in CTSIB in SSc patients.

PMID- 18833022
TI  - Partial and double-array implantation of the ossified cochlea.
AB  - OBJECTIVE: To review our experience with partial standard and double-array
      cochlear implantation in the ossified cochlea. STUDY DESIGN: Retrospective case
      review. SETTING: Tertiary referral center. PATIENTS: Twenty cochleae in 19 adult
      and pediatric patients with ossified cochleae. INTERVENTION(S): Patients
      underwent either partial insertion of a standard electrode array or double-array
      electrode insertion for their cochlear implantation. MAIN OUTCOME MEASURE(S):
      Number of electrodes inserted, number of active electrodes at follow-up, and open
      set speech performance. RESULTS: Twelve patients (four children and eight adults)
      had partial insertion of standard array electrode. The mean number of electrodes
      inserted and active at follow-up was 14.8 and 11.3, respectively. Eight patients
      (four children and four adults) had a double-array electrode implanted. The mean
      number of electrodes inserted and active at follow-up was 18.1 and 16.3,
      respectively. Open-set speech recognition was better in children regardless of
      duration of deafness. There were no complications. CONCLUSION: These findings
      suggest that the double array allows for more usable electrodes than in partially
      inserted cochlear implant. Compared with adults, children with ossified cochlea
      do well both in partial standard and double-array insertion. Both insertion
      techniques are safe, with no complications occurring in our patients. Straight
      and double arrays should be available in the operating suite for any patient in
      whom suspected cochlear ossification is confronted.

PMID- 18833023
TI  - Antibody responses after inactivated influenza vaccine in young children.
AB  - BACKGROUND: The frequency and duration of antibody responses after trivalent
      inactivated influenza vaccine (TIV) in young children are not well defined and
      assume greater importance with the expanded recommendations for vaccine use in
      children aged 6 months-5 years. METHODS: Forty-three children aged 6-23 months
      were vaccinated with TIV in the fall of 2002. At enrollment the majority of
      children were seronegative to one or more of the vaccine antigens and had no
      previously documented influenza. Postvaccination sera were collected in the
      subsequent fall and winter seasons. Acute antibody responses to TIV were
      determined using standardized hemagglutination inhibition (HAI) and
      neutralization assays. In calculating the duration of responses, sequential sera
      were analyzed to the last available sera, to the point at which antibody became
      undetectable, or to intercurrent influenza infection. RESULTS: Forty-three
      subjects contributed 121 sera that were analyzed for HAI responses to TIV. Four
      fold HAI rises after 2 doses of TIV in naive individuals were seen in 13 (72%) to
      H3N2, 22 (92%) to H1N1, and 15 (60%) to influenza B. Fewer 4-fold rises were seen
      in those with preexisting antibody. The results of microneutralization assays to
      H3N2 correlated well with HAI results. The time for antibody to decay to one-half
      of the postvaccination titer (t1/2) was approximately 126 days for H1N1 and 258
      days for H3N2. CONCLUSIONS: Although not all children responded with 4-fold rises
      in antibody or achieved the putative protective titer of > or =1:32, the half
      life of antibody suggested that children immunized in the fall should have immune
      responses sustained throughout the ensuing influenza season.

PMID- 18833024
TI  - Human immunodeficiency virus-infected boy with Stevens-Johnson syndrome caused by
      nevirapine.

PMID- 18833025
TI  - Amoxicillin for postexposure inhalational anthrax in pediatrics: rationale for
      dosing recommendations.
AB  - We reviewed information about the safety and plasma pharmacokinetic data for
      amoxicillin, specifically related to its potential use for postexposure
      inhalational anthrax. Amoxicillin (45 mg/kg/d) given orally in 3 divided doses to
      pediatric patients <40 kg should yield an adequate time above the MIC for
      susceptible Bacillus anthracis (< or =0.5 microg/mL) over most of the dosing
      interval (75-100%). Doses <45 mg/kg/d and dosing intervals longer than 8 hours
      should not be used for postexposure inhalational anthrax.

PMID- 18833026
TI  - Respiratory viral infections in children with leukemia.
AB  - BACKGROUND: Respiratory viruses occur frequently in the community and are a
      common cause of fever in children. Data on respiratory viral infections in
      children with cancer are limited. METHODS: A long-term, prospective, multicenter
      study was carried out in Finland searching for respiratory viruses in febrile
      children with leukemia. For this purpose, 138 febrile episodes in 51 children
      with leukemia were analyzed. Twelve types of respiratory viruses were searched
      for by viral culture, antigen detection, and polymerase chain reaction tests.
      RESULTS: Evidence of a respiratory viral infection was found in 61 of 138 febrile
      episodes (44%), accounting for an incidence of 0.8 (range, 0-2.4) per person year
      at risk during the treatment of leukemia. The most common viruses detected were
      rhinovirus (22%), respiratory syncytial virus (11%), human bocavirus (5%), and
      influenza A virus (4%). Dual viral infections were detected in 12 cases (9%).
      Half of the children had respiratory symptoms with cough being the most common
      symptom. Two children developed pneumonia. The mean duration of fever was 2.6 (SD
      1.7) days in children with respiratory viral infection and 2.1 (SD 1.3) days in
      children without evidence of viral infection (P = 0.44). CONCLUSIONS: Respiratory
      viruses are found commonly during febrile episodes in children with leukemia. The
      detection of viruses permits the use of available antiviral agents, may explain a
      poor response to antimicrobial agents, and minimizes the proportion of febrile
      episodes without possible etiologic agents in children with leukemia.

PMID- 18833027
TI  - Human bocavirus infection in children with respiratory tract disease.
AB  - BACKGROUND: Human bocavirus (HBoV) is a ubiquitous, newly described member of the
      Parvoviridae family frequently detected in the respiratory tract of children, but
      only few reports provide data proving the link between HBoV and respiratory tract
      disease (RTD). OBJECTIVES: To evaluate the incidence of HBoV infection in
      children with RTD; to analyze the clinical features of HBoV infection; and to
      clinically compare HBoV, respiratory syncytial virus (RSV), and human
      metapneumovirus (HMPV) infections. STUDY DESIGN: A prospective 1-year study was
      conducted in children <5 years of age hospitalized with RTD and in asymptomatic
      control children. RESULTS: Human bocavirus was detected in 55 (10.8%) of the 507
      children tested and in none of the 68 asymptomatic control children (P = 0.01).
      About 80% of these infections occurred between November and March. Coinfection
      with another virus was observed in 22 (40%) of the HBoV-positive children. HBoV
      viral load was significantly higher in samples from children with HBoV
      monoinfection than in those with coinfection. Subsequent detection of HBoV more
      than 2 months after the initial detection could be documented in 3 children.
      Clinical features associated with HBoV infection were similar to those observed
      with either RSV or HMPV infections, but HBoV infections were less severe than RSV
      infections. CONCLUSIONS: The difference observed in HBoV prevalence between
      children with RTD and controls provides support for a role of this virus in RTD.
      The frequent associations of HBoV with other respiratory viruses might be
      explained by the persistence of HBoV in the respiratory tract. The significance
      of HBoV viral load in nasopharyngeal secretions as a marker of pathogenicity
      merits further investigation.

PMID- 18833028
TI  - Leuconostoc bacteremia in pediatric patients with short bowel syndrome: case
      series and review.
AB  - INTRODUCTION: Infections caused by Leuconostoc species are rare with most
      reported cases occurring in immunocompromised patients. This article presents 6
      new cases of pediatric patients with short bowel syndrome who developed
      Leuconostoc bacteremia, and compares these cases with those previously reported
      in the literature. MATERIALS AND METHODS: This is a retrospective, descriptive
      study (January 2001 to May 2007) performed in a tertiary care teaching center.
      Hospitalized patients younger than 18 years of age, with multiple positive blood
      cultures for Leuconostoc spp. were evaluated. The collected data were compared
      with 10 similar previously reported cases. RESULTS: Six new cases of pediatric
      patients with short bowel syndrome who developed Leuconostoc bacteremia were
      identified. All 6 patients had received total parenteral nutrition and had
      central venous access, while 3 of these patients also received enteral nutrition.
      These results are similar to those reported in the literature. Only one of the
      newly reported patients had received vancomycin therapy before detection of
      Leuconostoc in the blood, whereas all prior reported cases had previously
      received this antimicrobial agent. Molecular analysis identified Leuconostoc
      mesenteroides as the most common species (4 cases) detected. CONCLUSIONS: This
      report expands on the number of cases of Leuconostoc bacteremia in pediatric
      patients with short bowel syndrome and shows that prior vancomycin is not a
      required risk factor for the development of this infection. As previously
      reported in the literature, the presence of a central venous catheter and
      disrupted bowel mucosa are risk factors for Leuconostoc bacteremia.

PMID- 18833029
TI  - Epstein-Barr virus load in cerebrospinal fluid of patients with chronic active
      Epstein-Barr virus infection.
AB  - Chronic active Epstein-Barr virus (EBV) infection is a rare chronic mononucleosis
      syndrome involving clonally proliferating EBV-infected T-/NK-cells. EBV DNA was
      quantified in nonpleocytotic cerebrospinal fluid (CSF) of 9 patients. Three
      patients with neurologic and/or neuroimaging abnormalities showed high CSF copy
      numbers. In 1 patient, CSF copy number exceeded the peripheral blood value. CSF
      EBV-load may predict the central nervous system involvement of EBVT-/NK-cells.

PMID- 18833031
TI  - Alkaloids induce programmed cell death in bloodstream forms of trypanosomes
      (Trypanosoma b. brucei).
AB  - The potential induction of a programmed cell death (PCD) in Trypanosoma b. brucei
      by 55 alkaloids of the quinoline, quinolizidine, isoquinoline, indole, terpene,
      tropane, steroid, and piperidine type was studied by measuring DNA fragmentation
      and changes in mitochondrial membrane potential. For comparison, the induction of
      apoptosis by the same alkaloids in human leukemia cells (Jurkat APO-S) was
      tested. Several alkaloids of the isoquinoline, quinoline, indole and steroidal
      type (berberine, chelerythrine, emetine, sanguinarine, quinine, ajmalicine,
      ergotamine, harmine, vinblastine, vincristine, colchicine, chaconine, demissidine
      and veratridine) induced programmed cell death, whereas quinolizidine, tropane,
      terpene and piperidine alkaloids were mostly inactive. Effective PCD induction
      (EC(50) below 10 microM) was caused in T. brucei by chelerythrine, emetine,
      sanguinarine, and chaconine. The active alkaloids can be characterized by their
      general property to inhibit protein biosynthesis, to intercalate DNA, to disturb
      membrane fluidity or to inhibit microtubule formation.

PMID- 18833030
TI  - A comparison of clinical and immunologic features in children and older patients
      hospitalized with severe cholera in Bangladesh.
AB  - BACKGROUND: : Infection with Vibrio cholerae induces protection from subsequent
      severe disease, suggesting that an effective vaccine could be an important
      preventive strategy. Available vaccines provide less protection against cholera
      than natural infection, particularly in children. METHODS: : We examined a cohort
      of 121 children (2 years-12 years of age) and 276 older patients (>12 years of
      age) hospitalized with cholera in Dhaka, Bangladesh over a 4-year period, to
      compare clinical features in older patients and children and immune responses to
      key antigens. RESULTS: : Older patients had more severe disease. Children with
      cholera were more commonly retinol deficient, while zinc deficiency was equally
      prevalent in both groups. Children developed higher vibriocidal and serum immune
      responses to the B subunit of cholera toxin (CTB). In contrast, older patients
      mounted higher immune responses to 2 other key V. cholerae antigens, the
      lipopolysaccharide (LPS) and toxin coregulated pilus antigens (TcpA). We compared
      immune responses following infection with those occurring after receipt of a
      live, oral vaccine in both children and older patients in Bangladesh, during a
      similar time period. The response rates for vibriocidal and LPS antibodies were
      higher after infection than after vaccination. Both vaccinated older patients and
      children responded poorly to CTB and TcpA. CONCLUSIONS: : Although children
      developed vigorous vibriocidal and CTB-specific responses following infection,
      they had lessened responses to LPS and TcpA compared with older patients, as well
      as lessened responses to vaccination. More studies need to be carried out to
      determine factors, including micronutrient interventions that can improve
      responses in children to both natural infection and vaccination.

PMID- 18833032
TI  - Influenza vaccine 2008-2009.
AB  - Annual immunization against influenza A and B is the most effective method of
      preventing infection and has been shown to reduce influenza complications.
      Changes this year include a vaccine with three new influenza antigens and
      expanded age criteria to include all children 6 months to 18 years of age. An
      upcoming issue of The Medical Letter will review drugs for prophylaxis and
      treatment of influenza.

PMID- 18833033
TI  - Dutasteride (Avodart) with tamsulosin (Flomax) for benign prostatic hyperplasia.

PMID- 18833034
TI  - [Genetic predeterminations of head and neck cancer].
AB  - The growing number of human cancers is the main reason for the search for new
      effective treatment strategies. The molecular basis for cancer transformation has
      to be elucidated in order to improve cancer treatment. It is stated that HNSCCs
      make up at least 5% of all registered malignant tumors in Poland. Exogenous
      factors influence HNSCC etiology. The prevalence of HNSCC is increased by several
      carcinogens, including tobacco smoke, life style, and others, such as oncogenous
      viral infections. It is more often emphasized that endogenous agents can also
      increase the risk of HNSCC development, especially genetic factors. The most
      recently characterized genetic factors for head and neck cancer are mutations in
      xenobiotic metabolism enzyme genes (GSTM1, GSTT1, GSTP1), suppressors mutations
      (TP53, RB1, BRCA1, ATM), polymorphisms of DNA repair genes (OGG1, XRCC1, XPD,
      RAD51), and mutations in mitochondrial DNA. It has been observed that single-gene
      polymorphisms could affect treatment, whereas the coincidence of other gene
      mutations may increase the risk of human head and neck cancer development.

PMID- 18833035
TI  - Alternate vehicles for diagnostic patch testing: an update.
AB  - AIM: The aim of the present study was to review the literature subsequent to 2001
      for recent information on alternate vehicles for diagnostic patch testing. AIM:
      Patch testing is a standard tool in dermatoallergology used in particular in the
      diagnostic process of allergic contact dermatitis. While petrolatum is employed
      in most cases, the way vehicles can influence results may not be neglected.
      Alternate vehicles may clarify hitherto negative or doubtful results. METHODS:
      The authors searched the most important medical databases using as search terms
      ''contact dermatitis'', ''patch test'' and ''vehicle''. RESULTS: Data obtained by
      local lymph node assay and in vitro percutaneous absorption experiments suggest
      methods to improve penetration and immunologic response by either adding
      substances to petrolatum or replacing it altogether. Still, an adequate
      hypoirritant substitute for petrolatum remains to be discovered. In addition, one
      study reveals the lack of a general recommendation as to which quantity of
      petrolatum, and therefore dose, to apply. In the meantime, a negative or unclear
      patch test in a patient with allergen exposition and maybe even a history of
      contact dermatitis might be repeated using the scratch method, a higher allergen
      concentration or sodium lauryl sulphate either in the vehicle or as a control.
      The authors review the literature subsequent to 2001 for recent evolution of
      knowledge on vehicles. CONCLUSION: Little conclusive research has been done on
      alternate vehicles in patch testing. However, the authors recognize some
      interesting tendencies as to either improve the characteristics of petrolatum as
      a vehicle by adding substances that may heighten the immunologic response or
      replace it.

PMID- 18833036
TI  - Vaccination strategies based on the mimotope concept.
AB  - Specific immunotherapies are in broad use for many diseases like allergies,
      cancer, autoimmune diseases or parasitic infections. Although clinical trials
      show successful application of these therapies, several disadvantages hinder the
      complete success. High production costs and repeated administrations represent
      the practical problems, while the possibly occurring side effects are the
      therapeutic troubles. To avoid these problems, the target specificity should be
      considered more intensely. Epitopes, the particular parts of antigens/allergens
      where they bind specific antibodies, are useful targets. To generate an epitope
      specific vaccination, mimotopes can be identified via the biopanning technology.
      Mimotopes are small peptides mimicking the epitopes in the structural as well as
      in the immunological point of few. They are able to induce antigen-specific
      antibodies in active immunization form. These antibodies are directed against the
      natural antigen/allergen, and therefore they are able to block the outbreak of
      the diseases. Current research focuses on the development of mimotopes to achieve
      an epitope-specific induction of blocking antibodies, e.g. for allergy treatment.
      In cancer therapy, studies with mimotopes show successful interference with tumor
      cell growth in immunizations of mice. Also in the case of autoimmune diseases and
      parasitic infections this method was applied, targeting different molecules,
      which are key mediators in the disease mechanisms. Through the mimotope treatment
      via the specific antibody production, the disease symptoms could be hampered.
      This review gives an overview of the use of the mimotope concept and also of
      related therapeutic trials for the treatment of allergy, cancer, autoimmune and
      infectious diseases.

PMID- 18833037
TI  - A possible role for vaccination in the treatment of psoriasis?
AB  - Psoriasis is a multifactorial immune skin disease whose etiology involves a
      strong genetic component, involving several genes encoding proteins involved in
      epidermal differentiation and immune, inflammatory and pathogen responses, in
      combination with microbial environmental factors. Although various microorganisms
      appear to provoke or aggravate the disease, including Staphylococcus aureus,
      Malassezia and Candida albicans, the association between S. pyogenes throat
      infections and guttate psoriasis is supported by the strongest clinical evidence.
      Furthermore, the identification of peptidoglycan-specific T cells in psoriatic
      skin lesions has led to the proposal that cell wall peptidoglycan may mediate the
      link between streptococcal infection in the tonsils and the subsequent induction
      of skin lesions. These findings suggest that psoriasis may be a possible
      candidate for therapeutic streptococcal vaccination. Current treatments for
      psoriasis have several limitations including toxicity and an increased risk of
      infection and malignancy. In contrast, vaccination could potentially induce long
      term tolerance without the side effects caused by global immunosuppression.
      Future research will need to address the identity of the triggering microbial
      antigen(s); such knowledge could open the way for vaccination as a therapeutic
      tool for psoriasis.

PMID- 18833038
TI  - A novel vaccine (Zostavax) to prevent herpes zoster.
AB  - Varicella-zoster virus is the causal agent of varicella and herpes zoster (HZ) in
      humans. HZ results from reactivation of latent varicella-zoster virus (VZV)
      within the sensory ganglia. The incidence and severity of HZ increase with
      advancing age; more than half of all persons in whom HZ develops are older than
      60 years. The most frequent debilitating complication is postherpetic neuralgia,
      a neuropathic pain syndrome that persists or develops after the dermatomal rash
      has healed, and can be prolonged and disabling. There are many limitations of the
      current therapies for HZ and postherpetic neuralgia. A live attenuated VZV
      vaccine has been developed and recently approved by the United States Food and
      Drug Administration (FDA) and the European Union for the prevention of HZ in
      individuals 60 years of age and older. In a randomized, double-blind, placebo
      controlled trial 38,546 adults of 60 years of age or older, the use of the HZ
      vaccine reduced the burden of illness due to HZ by 61.1% (P<0.001), reduced the
      incidence of postherpetic neuralgia by 66.5% (P<0.001), and reduced the incidence
      of HZ by 51.3% (P<0.001). In this review, the authors will discuss the history of
      the use of the varicella vaccine in children, and the subsequent development of
      the new HZ vaccine.

PMID- 18833039
TI  - Vaccinations against cutaneous Leishmania infection.
AB  - Cutaneous leishmaniasis is an endemic disease with increasing incidence, even in
      Europe. Recently, it has attracted more attention due to reactivation in
      immunocompromised hosts, e.g. in the context of HIV. Therapeutic options range
      from topical treatment to systemic therapy for more complex cases. A vaccine does
      not exist at present. Despite of several attempts, vaccine generation has proven
      to be difficult even though protective immunity against this obligate
      intracellular protozoan parasite is dependent on the development of antigen
      specific CD4+ and CD8+ T cells capable of releasing IFN?. IFN?, in turn,
      activates phagocytic host cells to generate oxidative radicals and to eliminate
      the parasite. This review will describe the basic immunology leading to the
      development of protective immunity in infected individuals. In addition, the
      authors will focus on highlighting the different approaches utilized for vaccine
      development and describe what a efficient vaccine may consist of. Combined
      intensive research in the fields of basic parasitology and immunology may allow
      for the generation of an efficacious vaccine against this important human
      pathogen in the near future.

PMID- 18833040
TI  - Immunotherapeutic strategies for the treatment of malignant melanoma.
AB  - The incidence of cutaneous malignant melanoma is increasing at a faster rate than
      any other cancer worldwide. Despite new advances in surgical management of
      melanoma, this malignancy remains one of the most aggressive and intractable to
      treat among other solid tumors. Continuous search for better therapeutics led to
      the development of various immunological approaches applicable to the treatment
      of this melanocytic malignancy. Multiple peptide, dendritic cell, adjuvant,
      lymphocyte, and virus-based strategies were established and tested in preclinical
      and clinical studies with varying degrees of clinical success. However, the most
      recent investigations in melanoma immunotherapy have clearly demonstrated that
      complex vaccines and the combination of different approaches, such as the use of
      dendritic cell vaccines in conjunction with costimulatory molecules, are superior
      to conventional immunization protocols in induction of tumor-specific immune
      responses. These recent studies open new perspectives for the development of
      efficient melanoma immunotherapeutics suitable for the treatment of primary and
      metastatic disease.

PMID- 18833041
TI  - Terbinafine-induced acute generalized exanthematous pustulosis.
AB  - Terbinafine is an allylamine antifungal agent, effective in the treatment of
      dermatomycoses. Many cutaneous adverse reactions have been reported (in about 3%
      of treated patients). Furthermore terbinafine has been associated with pustular
      eruptions, as well as the induction and exacerbation of pre-existing psoriasis
      and acute generalized exanthematous pustulosis (AGEP). AGEP is an uncommon
      aseptic pustular eruption, classified for many years as a pustular psoriasis,
      that usually follows recent administration of oral or parenteral drugs. The
      disease is most frequently triggered by antibiotics, most of all aminopenicillins
      and macrolides. Characteristic AGEP features include the sudden onset of fever
      above 38 C with widespread erythematous eruption, rapidly progressing to a fine,
      non-follicular, micropustular rash. Leucocytosis is generally present, sometimes
      associated with eosinophilia. The illness usually resolves spontaneously with the
      fever and the pustulation clearing within 15 days, sometimes followed by
      desquamation. Hystopathology shows non-follicular spongiotic pustules in the
      epidermis filled with neutrophils, a mixed perivascular infiltrate of neutrophils
      and occasional eosinophils with papillary dermal oedema. On this subject,
      Sideroff et al. recently elaborated a validation score based on morphology,
      histological criteria, and disease course. The pathogenetic mechanism which leads
      to the induction of AGEP by some medicines has still not been clarified, but T
      cells seem to play a crucial role. The authors report a case of a patient with
      terbinafine-induced AGEP and a review of the literature about this topic. The
      case illustrates once again the role of terbinafine in AGEP and reminds us that
      early diagnosis of AGEP is important to avoid unnecessary investigations and/or
      the administration of antibiotics.

PMID- 18833042
TI  - Zuska's disease.
AB  - Cutaneous signs and symptoms in subareolar abscesses of the breast or lactiferous
      fistula (Zuska's disease, ZD) are common and frequent, but generally
      dermatologist ignore this clinical entity. An epithelial squamous metaplasia
      causes plugging and obstruction of the ducts is a pathogenetic event. Subsequent
      inflammatory reaction and infection produce local and general symptoms. Nipple
      retraction, recurrent episodes of erysipela and presence of painful nodules under
      the areola in a non-lactating woman are suspect. The presence of a milky draining
      sinus in the areola is characteristic. The diagnostic challenge is to
      differentiate these benign condition from a breast cancer. Treatment with
      antibiotics in the acute and chronic phase is mandatory, surgical removal of
      abscess and duct is sometimes resolutive. The authors describe a case of ZD in a
      pathologically obese woman treated with a long term penicillin schedule with no
      favorable effects.

PMID- 18833043
TI  - Randomized prospective study on the efficacy of a new revitalizing filler
      composed of hyaluronic acid (Wipeline).
AB  - AIM: The aim of the study was to test the efficacy of a new revitalizing filler
      (Wipeline) formed by a buffer physiological solution of hyaluronic acid (HA).
      METHODS: A prospective study was performed on 100 patients (aging between 40 and
      70 years), with clear signs of premature facial aging. Patients were randomly
      assigned to two groups, one treated with a HA concentration of 1.6%, the other
      with a concentration of 2% in the tested product. The treatment protocol
      consisted of three sessions with a four weeks intervals between them. Visual
      Analogue Scale (VAS) and digital photos were used to evaluate results after 1, 3,
      6 and 12 months from treatment end. RESULTS: An improvement of turgidity,
      elasticity and luminosity of the skin and a reduction of folds and wrinkles of
      the treated areas were observed in both groups. The higher concentrated solution
      of HA had a more prolonged effect and a greater filling effect. Products were
      well tolerated and no adverse reactions observed. CONCLUSION: The efficacy of
      Wipeline has been clinically supported. This revitalizing filler succeeded in
      increasing skin elasticity and tone by dermal hydration. The procedure is simple
      and little invasive. It represents a good treatment option to restore vitality
      and turgidity of skin presenting the signs of aging.

PMID- 18833044
TI  - Safe use of efalizumab in a psoriasis patient with chronic heart failure due to
      hypertrophic cardiomyopathy.

PMID- 18833045
TI  - Alopecia areata and celiac disease.

PMID- 18833046
TI  - Enzyme-linked immunosorbent assay in autoimmune blistering diseases: preliminary
      experience of the Dermatology Department of Cagliari.
AB  - AIM: Recent insights on the pathogenesis of autoimmune blistering diseases have
      pointed out the opportunity of new diagnostic tools, such as enzyme-linked
      immunosorbent assay (ELISA) for Desmogleins 3 and 1 (Dsg3, Dsg1), and bullous
      pemphigoid (BP) 180 antigen auto-antibodies. The aim of the present prospective
      study was to evaluate the diagnostic values of these tests in blind with
      histopathology and direct immunofluorescence (DIF), the assessment of correlation
      with clinical presentation and severity of disease, as well as eventual
      modifications of serum auto-antibodies titres in course of treatment. METHODS:
      From June 2005 to June 2007, all consecutive patients with clinically blistering
      diseases presenting to the Dermatology Department of Cagliari were enrolled in
      the study. Biopsy specimens were performed in all cases and sent for
      histopathological examinations including haematoxylin-eosin stain and DIF to the
      Unit of Pathological Anatomy of the same University. Serum samples were tested
      with Dsg3, Dsg1 and BP180 ELISA in the internal laboratory of the Dermatology
      Department, and results were worked out many days before histopathology reports.
      Final diagnosis was established on clinical, histological and immunopathological
      findings. A selected sample of patients with active autoimmune blistering disease
      underwent repeated immunosorbent assays at 1-2-6 months from first diagnosis and
      treatment introduction. RESULTS: Forty-two patients (23 men, 19 women) were
      enrolled in the study and divided into three groups: pemphigus (N=17), pemphigoid
      (N=19) and other diseases (OD; N=6), depending on the final diagnosis assessed by
      histological, immunopathological and serological examinations. In pemphigus group
      ELISA showed circulating antibodies against Dsg3 in all patients (100%) and
      against Dsg1 in 13 patients (76.5%). In the pemphigoid group, 16 of 19 sera
      showed positive scores above the cut-off value (84.2%), but sensibility was
      higher if considering only the bullous pemphigoid final diagnosis (16/17). None
      of the other bullous diseases (0%) exceeded the cut-off value for Dsg1, Dsg3 and
      BP180 ELISA. Correlation with histopathology and direct immunofluorescence was
      excellent for pemphigus and very good for pemphigoid. Eight patients (6 P; 2 BP)
      underwent a serial measurement of the autoantibodies levels: two patients (1 PV
      and 1 BP) showed an ELISA antibodies titres decrease after two months of
      treatment, in parallel with an excellent clinical response. Whereas in six cases
      (5 PV and 1 BP) the ELISA titres overstayed high at I and II month. Clinically
      the disease was active in all six patients, and a treatment adjustment was
      performed (increased corticosteroid dosage and/or azathioprine initiation in all
      cases, high dose intravenous immune globulin in one case). At month VI, a
      decrease on ELISA antibody levels was documented in three patients (3 PV),
      parallel to a clinical remission. Whereas in other three patients (2 PV, 1 BP),
      persistent high Dsg3 ELISA titres were related to a still active disease:
      although clinically improved, blisters flared up at any attempt to taper drugs
      dosage. CONCLUSION: Dsg3, Dsg1 and BP ELISA is a sensitive, easy and quick
      reading tool for the diagnosis of the main autoimmune blistering diseases:
      pemphigus and bullous pemphigoid. More over, autoantibodies titre correlate with
      disease severity, and is useful to monitor treatment response.

PMID- 18833047
TI  - Narrowband UVB phototherapy in vitiligo: evaluation of results in 53 patients.
AB  - AIM: Narrowband UVB (NBUVB)phototherapy has been used for vitiligo for years, but
      today there are no standardized protocols of treatment and follow-up data. A long
      term study on 53 patients with localized or diffuse vitiligo is presented with
      the aim at improving the data availability in the literature. METHODS:
      Phototherapy was administered two times a week on non-consecutive days; the
      treatment was continued for one year. The mean total dose administered was 201.28
      J/cm2.The response to phototherapy was expressed as percentage of repigmentation:
      a repigmentation greater than 75% was considered excellent, a repigmentation
      between 74% and 50% good, a repigmentation between 49% and 25% moderate, a
      repigmentation less than 24% mild. In case of absence of repigmentation, the
      patient was judged as non-responder RESULTS: Three point eight percent of
      patients showed excellent response, 32.05% good response, 32.05% moderate
      response, 28.3% mild response, while the remaining 3.8% was not responsive.
      According to statistical analysis best responses, were observed in non-acral
      areas (P<0.001), in patients with recent vitiligo (P=0.003), in patients with
      negative family history for vitiligo (P=0.038), and in those not exposed to
      previous therapies (P=0.005). In 36 patients a mean follow-up of 19.78 months was
      obtained. CONCLUSION: NBUVB phototherapy is useful and safe for vitiligo, but in
      the future it will be necessary to compare results of different studies using the
      same treatment protocols and to obtain data of series endowed with an adequate
      follow-up.

PMID- 18833048
TI  - The regulatory T-cell phenotype in progressive mycosis fungoides.
AB  - In early stages mycosis fungoides (MF) often runs an indolent course.
      Nevertheless a small but significant part of these patients develop an
      aggressive, life threatening course. These patients usually were
      immunocompromised. In most of those cases the lymphoma cells express CD25. This
      raised the question if those lymphomas may express a regulatory phenotype.
      Recently a couple of in vitro and in vivo studies analyzed this issue with
      different methods. This review discusses the recent developments in this highly
      topical area of research.

PMID- 18833049
TI  - Flow cytometry for the diagnosis of mycosis fungoides.
AB  - The diagnosis of mycosis fungoides (MF) remains difficult even with current
      immunohistochemical and molecular techniques. Flow cytometry is a technology
      widely used for the diagnosis of hematologic malignancies in all areas of
      hematopathology but has not been readily applied for the diagnosis of MF. In this
      article the Authors review two issues that affect the ability to diagnosis of MF
      by flow cytometry, lymphocyte cell recovery from skin biopsies and identifying T
      cell neoplasia through alteration of the normal T cell phenotype. They present
      data from their recently published study and others that demonstrate that cell
      recovery is, in fact, adequate for diagnosing MF in the vast majority of cases.
      Moreover, they illustrate techniques used to identify neoplastic T cells that
      help in the analysis of skin biopsy specimens suspected of harboring a T cell
      malignancy. Finally, they discuss the power of flow cytometry for the diagnosis
      of cutaneous T cell lymphomas (CTCL). They argue that the capabilities of current
      flow cytometric techniques for the diagnosis of MF should allow for enhanced
      diagnostic accuracy and classification of CTCLs.

PMID- 18833050
TI  - Cutaneous T cell lymphoma: translating immunobiology into therapeutic
      opportunities.
AB  - Cutaneous T cell lymphoma (CTCL) has always served as a proving ground where
      conceptual advances in immunology can be tested and the results translated into
      clinical practice. From the earliest studies that used sheep red blood cells to
      identify the malignant cell as a T lymphocyte to molecular demonstration of the
      clonalilty of the disease, basic science techniques have provided sign posts that
      allow us to understand the clinical features seen in the patients. We continue to
      apply this paradigm to develop new insights into the role of the immune system in
      CTCL with the goal of using this knowledge to enhance the therapeutic options
      available to the patient. This article will review the studies that have led to
      our current understanding of the immunobiology of CTCL and the new therapeutic
      approaches that are being tested in this disease.

PMID- 18833051
TI  - Interleukins in the treatment of mycosis fungoides.
AB  - Mycosis fungoides is typified by a cutaneous infiltrate of CD4+ lymphocytes with
      a Th2 phenotype. As the disease advances, there is increased expression of Th2
      cytokines. This results in a subsequent suppression of Th1 cytokines and impaired
      cell mediated cytotoxic host response to the lymphoma cells. Disarming this cell
      mediate cytotoxic immune response creates a relentless cycle of disease
      progression. A cell mediated cytotoxic immune response can be stimulated with the
      use of Th1 cytokines such as IL-2 and IL-12. In this report, the Authors review
      the rational for the use of these particular cytokines in the treatment of
      mycosis fungoides. Further they comment on the experience and success regarding
      these two agents in phase I and II trials for the treatment of mycosis fungoides.
      Lastly, they discuss other potential cytokine therapies which could play a role
      in the future treatment of mycosis fungoides.

PMID- 18833052
TI  - Immunotherapy as an adjuvant therapy in the management of advanced, surgically
      resected, melanoma.
AB  - Metastatic melanoma continues to be one of the most devastating of all cancers.
      It is a heterogeneous solid tumor whose treatment is challenging and difficult.
      It afflicts thousands of otherwise healthy patients annually, and clinicians have
      yet to discover an effective treatment for locally advanced disease. Over the
      years, much attention has been devoted to the development of an effective
      adjuvant treatment for patients with resected melanoma who remain at high risk
      for recurrence. The new advances in the understanding of melanoma's
      microenvironment and the complexity of its disease process, makes it clear that
      the treatment approach to this disease needs to be multi-directional. Numerous
      studies have tested various immunotherapeutic strategies in the treatment of
      advanced melanoma, in particular. These strategies include melanoma vaccines,
      interferon-alpha, interleukin-2 (IL-2), and dendritic cell vaccines. The Dr.
      Wallack's Surgery Research Laboratory has been studying melanoma vaccines for the
      past three decades. The first generation melanoma vaccine proposed by the
      Laboratory showed promising results in a subset of patients. Recently, the same
      Laboratory has produced a second generation melanoma vaccine (DC-Melvac) that
      consists of five human melanoma cell lines, a recombinant vaccinia virus that
      encodes for IL-2, as well as dendritic cells that have been programmed to
      recognize certain melanoma associated antigens. DC-MelVac was recently approved
      by the Food and Drug Administration for its use in Phase I clinical trials. These
      trials are expected to be underway in the near future. The ensuing review
      discusses many of the immunotherapeutic strategies that have been studied in the
      treatment of melanoma, including DC-MelVac.

PMID- 18833053
TI  - Experiences with implementation of evidence-based prevention programs to prevent
      occupational skin diseases in different occupations.
AB  - Occupational skin diseases are among the most frequently recognized occupational
      diseases in many industrialized countries. This paper describes and review
      experiences with implementation of interventions to prevent occupational skin
      diseases in different occupational settings representing the food processing
      industry and a hospital. The study populations were gut cleaners with all
      participants being exposed to wet work, cheese dairies and a hospital where all
      employees were included. The effect of implementation of evidence-based
      prevention programs were tested by questionnaire surveys on baseline and follow
      up. A significant reduction in eczema at hands or forearms was observed among gut
      cleaners. At cheese dairies the eczema frequencies were low except for a
      comparison dairy where significant changes were seen. At the hospital a non
      significant reduction in hand eczema was observed. Changes related to use of
      protective measures and knowledge on prevention of occupational skin diseases
      were observed. A process evaluation carried out at the gut cleaning departments
      showed association between the eczema frequency at follow-up, activities related
      to prevention and implementation of an occupational health management system. In
      addition to documenting the scientific background for evidence-based prevention
      programs to prevent occupational skin diseases in different occupations, both the
      study population and the study design should be considered carefully when testing
      the implementation of workplace interventions. These aspects may influence the
      outcome in different directions and either facilitate or hamper the possibilities
      to provide scientific documentation of the effect of the intervention tested.

PMID- 18833054
TI  - Secondary syphilis with intestinal involvement: description of a case.
AB  - As it is well-known, during secondary syphilis, it is possible to observe a
      systemic involvement of the treponemal infection. The visceral localizations are
      rarely observed, and they usually present themselves as asymptomatic or with
      aspecific symptoms. This report concerns a case of a homosexual patient who
      referred to us in order to perform blood tests for the main sexually transmitted
      diseases (HIV, HBV, HCV, TPEIA). Moreover, he reported a history of palmo-plantar
      erythematous desquamative lesions, spontaneously resolved. For this reason all
      the serological tests for syphilis have then been performed. Once the diagnosis
      of recent syphilis was made, and the antibiotic therapy with penicillin begun,
      the patient reported to have fever, abdominal pain and diarrhoea. The
      gastroenterological consultation highlighted the presence of a chronic active
      granulomatous colitis, but excluded an inflammatory or autoimmune aetiology.
      Because of this findings, and also because of additional histopathological
      examinations of the colon, the diagnosis of recent syphilis with intestinal
      involvement was made. The present case report confirms, once again, how the
      nickname ''great imitator'' is appropriate for calling syphilis. It highlights
      moreover that, as the incidence of syphilis is arising, in the presence of
      intestinal symptoms of unknown origin in patients with a history of unprotected
      sexual intercourse, syphilis should always be comprised among the possible
      diagnoses.

PMID- 18833055
TI  - Ano-rectal lymphogranuloma venereum: the first case in Italy.
AB  - Lymphogranuloma venereum (LGV) is a sexually transmitted infection endemic in
      Central Africa, South-East Asia and in some countries of Central and South
      America. In Italy LGV has been sporadically reported in patients coming from
      abroad. The etiological agent of LGV is Chlamydia trachomatis serovars L1, L2,
      L3, differentiating by pathogenetic action. The clinical course of LGV can be
      divided into three stages with a initial small papule, which may ulcerate, at the
      site of inoculation, followed by massive lymphadenopathy, which is usually
      unilateral, and eventually by lymphatic obstruction, causing elephantiasis.
      During 2004 a LGV ano-rectal clinical variant has been described as an erosive
      proctitis among homosexual HIV-positive men in some countries of Western Europe,
      not coming from endemic areas. Until now this syndrome has been often explained
      as chronic intestinal inflammatory disease. This report describes a case of
      proctitis caused by CT serovar L2; to Authors' knowledge this is the first case
      reported in Italy.

PMID- 18833056
TI  - Papulo-pustular eruption during cetuximab treatment.

PMID- 18833057
TI  - Zosteriform lichen planus.

PMID- 18833058
TI  - Collagen IV, laminin, fibronectin, vitronectin. Comparative study in basal cell
      carcinoma. Correlation between basement membrane molecules expression and
      invasive potential.
AB  - AIM: Basal cell carcinoma (BCC) is a malignant carcinoma arising by cells of
      epidermal basal layer and adnexal epithelium. It appears intimately connected
      with a stromale component that holds a relevant role for tumour's evolution. It
      occurs frequently on sun-exposed regions, and is considered as low potential for
      metastasis, whereas its local invasion, destruction and recurrence are well
      known. METHODS: Particularly formalin-fixed, paraffin-embedded tissue from 40
      cases of BCC, 20 recurring and 20 not recurring, had been studied, with
      immunohistochemical techniques to value the distribution of intrinsic and
      extrinsic components of basal membrane. RESULTS: The immunohistochemical
      examination showed collagen IV and laminin continuous positivity in peripheral
      cells, seating around neoplastic nests of 62.5% not recurring BCC. The same
      antigens exhibited discontinuous positivity in cells with non distinguished
      borders, seating around nests of 85% micronodular recurring BCC. The valuation of
      fibronectin and vitronectin could have a more significant prognostic value.
      Fibronectin in fact appeared hyper-expressed in peritumoral stroma of 80%
      recurring BCC, vitronectin appeared less expressed than normally in peritumoral
      stroma of 95% recurring BCC. CONCLUSION: A correlation between basal membrane's
      break and carcinoma's recurrence has been noticed. This shows the utility of
      other prognostic factors helping the valuation of malignant progression.

PMID- 18833059
TI  - Contact allergy to cosmetics: the patients' perspective. An interview-based
      study.
AB  - AIM: It is generally agreed that the management of allergic contact dermatitis
      (ACD) to cosmetic ingredients can be challenging for patients due to the complex
      names and synonyms of the responsible allergens, but what kind of problems
      patients actually have in finding safe alternative products has seldom if ever
      been investigated. METHODS: To identify the major problems experienced by
      patients allergic to cosmetics, the authors studied 72 ACD patients with
      clinically relevant positive patch test and/or repeated open application test
      (ROAT) reactions from cosmetic allergens or from own cosmetic products as is. Two
      months after patch testing, they were called by phone, and underwent a semi
      structured interview focused on the following questions: ''Is your dermatitis
      better?'', ''Did you find our explanations clear?'', ''Do you remember the name
      of the substance you are allergic to and which products contained it?'' ''Was it
      difficult to avoid exposure? If yes, why?'', ''How did you chose alternative
      products?''. RESULTS: The interview revealed that 63 out of 72 patients were
      cured or much improved. Of the remaining 9 patients, 6 had not avoided exposure,
      3 still suffered from other kinds of dermatitis, but ACD was no longer present.
      All patients declared themselves satisfied with the explanations received, but
      half of them could not precisely name the causative allergens/cosmetics and had
      had problems in finding safe products, especially when preservatives with
      difficult names were involved. Hypo-allergenic-products were often complained of
      as expensive. Twenty patients who had been prescribed specific allergens-free
      products by their dermatologists had overcome their problems more easily.
      CONCLUSION: Patients' education after patch testing is crucial to achieve quick
      and stable resolution of ACD from cosmetic products.

PMID- 18833060
TI  - Cutaneous sarcoidosis in Tunisia.
AB  - AIM: Sarcoidosis is a multisystem disease of unknown etiology characterized by
      granulomatous infiltration. As clinical features vary among patients from
      different ethnic groups and geographic areas, local reports are of great
      interest. The aim of this study was to make an inventory of the clinical
      presentation of cutaneous sarcoidosis in Tunisia. METHODS: The study was
      conducted in an academic teaching hospital, inpatient and outpatient department.
      The authors retrospectively reviewed the medical records of all patients
      diagnosed with sarcoidosis at the Dermatological Departement of Charles Nicolle
      teaching Hospital, Tunis, within a 32-year period. RESULTS: One hundred and
      eighteen patients were diagnosed to have sarcoidosis, corresponding to 25 males
      and 93 females. Mean age at presentation was 39.5 years. Childhood sarcoidosis
      represented 14.4% of cases. Cutaneous involvement was dominated by micronodular
      lesions. Chest X-rays abnormalities were present in 28 patient/93 (30.1%). Most
      of them were at stage 1 or 2. Peripheral lymph node enlargement was reported in
      15 patients (12.7%). Other internal organ involvements corresponded to: eyes (15
      cases); bones (12 cases), joints (5 cases), gasto-intestinal tract (5 cases),
      upper airways (5 cases), liver (4 cases), kidney ( 1 case) and muscles (1 case).
      Systemic involvement was noticed in 88% patients with lupus pernio. Treatment
      modalities included topical and oral corticosteroids, hydroxychloroquine,
      allopurinol and surgical excision with variables outcomes. CONCLUSION: The data
      of this study suggest that sarcoidosis manifests with a wide range of cutaneous
      lesions in Tunisian patients and that extracutaneous involvement is not rare.
      Remarkable clinico-epidemiological characteristics are the clear predominance in
      women, the high frequency of childhood cases and the predominance of micronodular
      skin lesions.

PMID- 18833061
TI  - Proposed guidelines for use of dermal and subdermal fillers.
AB  - The great variety of injectable substances for esthetic treatments and their many
      adverse effects evidence the necessity for agreement among the experts who use
      such substances. The guidelines to be followed should take into consideration the
      ideal features of a filler, the criteria of choice (anatomic area, type of
      imperfection), well established procedures, medical-legal issues (medical charts
      and informed consent), and typical responses of different anatomic areas.

PMID- 18833062
TI  - Cytokines and Langerhans cells in allergic contact dermatitis.
AB  - Contact hypersensitivity (CHS) is a dendritic cell (DC)-dependent T-cell mediated
      cutaneous inflammatory reaction elicited by epicutaneous exposure to reactive
      chemicals, known as haptens, from cosmetic products or through environmental and
      occupational exposures. The best-studied haptens are low molecular weight
      chemicals (<1,000) that bind discrete amino acid residues on self or exogenous
      proteins/peptides in the skin and become immunogenic. Clinically, CHS typically
      occurs as a delayed type of allergic contact dermatitis. Haptens penetrate the
      skin and bind to self proteins to form complete antigens which are taken by
      antigen presenting cells to start a cascade of actions resulting in a delayed
      hypersensitivity reaction. Larger molecules such as proteins induce response
      involving the humoral immune system. The environment at the time of antigen
      presentation affects the innate immune system which in turn influences the
      expression of CHS. The subsequent immunologic response (or lack thereof) is a
      result of complex interaction between both the innate and the adaptive immune
      systems. This interaction results in either an inflammatory immune response or
      tolerance.

PMID- 18833063
TI  - Management of irritant contact dermatitis: continuously a problem for patients
      and dermatologists.
AB  - Skin irritants may induce irritant contact dermatitis (ICD) in various ways but
      the end result remains the same: a clinical picture which in most cases is
      practically indistinguishable from allergic contact dermatitis (ACD). A treatment
      that works for ACD does not necessarily work for ICD. Management has to focus on
      preventive measures, education of people exposed to irritants and supportive
      topical treatment of varying nature depending on the clinical circumstances.

PMID- 18833064
TI  - Teledermatology.
AB  - Dermatology is perhaps the most visual specialty in medicine, making it ideally
      suited for modern telemedicine techniques, as has been shown in a number of
      recent studies investigating feasibility and reliability of teledermatology. It
      has generally demonstrated high levels of concordance in diagnosis and management
      plans compared with face-to-face consultations. Teledermatology has been also
      used for various purposes, including triage, diagnostic and management services,
      and second opinion services for primary care practitioners. It has been set up in
      a number of ways: 1) direct referral for primary care using images and clinical
      history sent to secondary care dermatology services for second opinion and for
      triage referrals; and 2) facilitating community-based clinics led by nurses or
      general practitioners. Moreover, in the last years new fields in teledermatology
      have grown up. Teledermoscopy is a promising area for melanoma screening as well
      as for diagnosis and management of equivocal pigmented skin lesions. The
      feasibility of mobile teledermatology and mobile teledermoscopy has been recently
      proved and these new facilities have the potential to become an easy applicable
      tool for everyone and may open the door for a new flexible triage system for
      detection of skin cancer in general and melanoma in particular. The
      implementation of virtual slide systems for teledermatopathology has allowed
      avoiding the limitations imposed by conventional photographs. Finally, web
      consultations in dermatology are a rather new tool that became available in the
      last years and teledermatologic services through the Internet offer many
      possibilities, including continuing medical education, on-line atlases and
      databases, and specific web application suited for teledermatology (i.e.
      www.telederm.org).

PMID- 18833065
TI  - A case of difficult Pyoderma gangrenosum diagnosis. Case report.
AB  - We report a case of Pyoderma gangrenosum of difficult diagnosis due to its
      gradual and slow evolution. We believe that cyclosporine A is a valid drug in the
      management of this strange disease.

PMID- 18833066
TI  - A case of ''silk route disease'' in a patient from Congo.
AB  - The authors describe a case of Behcet's syndrome or ''silk route disease'' in a
      patient from the Democratic Republic of Congo. The patient arrived in hospital
      suffering from an acute episode of febrile erythema nodosum, which was diagnosed
      as type 2 leprosy reaction. His history reported recurrent oral aphthae and
      during hospitalization ulcers on the scrotum and pathergy were observed. A
      diagnosis of Behcet's disease was made. The patient is HLA B51 negative and the
      scientific literature confirms that testing for the presence of this allele is
      negative in the 10 cases of Behcet's disease reported from Sub-Saharan countries.

PMID- 18833067
TI  - Erythema multiforme-like eruption induced by contact dermatitis caused by topical
      corticosteroids.

PMID- 18833068
TI  - Alopecia areata and autoimmunity.
AB  - AIM: The aim of the present study was to estimate the association between
      alopecia areata (AA) and autoimmunity. To such scope, the authors have estimated
      the presence of autoantibodies in patients with alopecia areata joints to the
      authors' observation in the last two years. METHODS: In 63 patients affected with
      different forms of AA (45 cases with multiple patches, 10 with single patch, 5
      with alopecia totalis and 3 with alopecia universalis), has been estimated a
      autoantibodies panel. In 28 subjects (44%) it has been evidenced the presence of
      autoantibodies; in particular, 23 subjects were affected from AA with multiple
      patches, 3 from single patch, 1 from alopecia totalis and 1 from alopecia
      universalis. RESULTS: The autoantibodies against thyroperoxidase and
      thyroglobulin were found more frequently, followed from antimicrosomal and
      antinuclear. Except in 5 subjects with autoimmune disease (4 from thyroiditis and
      1 from subacute cutaneous lupus erythematosus), all the other cases turned out
      positives were asymptomatic, then the skin behaved like ''organ proof'' of an
      organ pathology. On this purpose, in 17 cases (27%) it has been revealed an
      autoimmune thyroiditis. CONCLUSION: AA is often associated to other autoimmune
      diseases and that in the 36% of the cases it has permitted to reveal a silent
      pathology of organ.

PMID- 18833069
TI  - Psychogenic alopecia.
AB  - AIM: It has been seen that hair loss entails a perceived loss of personal
      attractiveness combined with the fear of growing old, and it presents negative
      repercussions on social life associated with a frequent reduction in mood tone.
      It has also been observed that the quality of life worsens in patients suffering
      from this problem. Other studies cast doubt on a cause-effect link of this
      nature, suggesting the possibility that hair loss might be secondary to a
      psychological condition of personal unease. Seen in this light, alopecia should
      be classified as a fully fledged psychosomatic disease. The aim of this study was
      to evaluate the possibility that psychological aspects could play a causal role
      also in the genesis and persistence of hair loss. METHODS: A group of 29 patients
      were enrolled in the study with widespread hair thinning, more marked in the
      ''front median'' area, all patients presented hair thinning and hyperseborrhea.
      RESULTS: Of the 29 patients undergoing psychodiagnostic evaluation, 27 showed the
      presence of depressive symptoms. CONCLUSION: This study underlines how psychic
      aspects can play a decisive role in the genesis and persistence of hair loss,
      prompting us to hypothesise a new nosographic entity that can be called
      psychogenic alopecia.

PMID- 18833070
TI  - Vasoactive peptides in the pathogenesis of psoriasis.
AB  - Psoriasis, a chronic inflammatory skin disease, is believed to be exacerbated by
      stress. The exact mechanism of this phenomenon is not fully understood, however,
      it has been postulated that different substances released from dermal nerve
      endings during stress may take part in initiation or modulation of psoriasis. One
      of the most interesting group of mediators are polypeptides, also named as
      neuropeptides, that possess vasoactive properties. It was documented that these
      polypeptides could not only be released from nerve endings, but may also be
      directly synthesised in the skin and liberated from numerous dermal cells.
      Moreover, these substances are not only released by different cells, but may
      activate various cell types showing a wide spectrum of biological actions. Thus,
      this complex system of interactions seems to be important component of psoriatic
      pathological reaction. The significant role of these neuromediators has also been
      postulated in other chronic skin diseases, like palmoplantar pustulosis, atopic
      and irritant eczema, rosacea, lichen sclerosus, vitiligo, pigmented urticaria or
      prurigo nodularis. Among different neuropeptides, substance P, calcitonin gene
      related peptide, vasoactive intestinal peptide (VIP) and neuropeptide Y have been
      mostly studied in psoriasis.

PMID- 18833071
TI  - Genetic variation and psoriasis.
AB  - Psoriasis is a common chronic inflammatory skin disease with a strong genetic
      basis, characterized by complex alteration in epidermal growth and
      differentiation. The genetic basis of psoriasis has been appreciated for nearly
      100 years, but only recently have several of the genetic variants involved in
      psoriasis pathogenesis been identified. These genetic variants so far identified
      are the HLA-Cw*0602 allele of the HLA-C gene on chromosome 6, the p40 subunit of
      the IL-12 and IL-23 cytokines (IL12B), the IL-23 receptor and SNF313, a gene
      implicated in protein ubiquitinylation. Psoriasis patients have also been shown
      to have an increased number of copies of the beta-defensin gene cluster on
      chromosome 8. Beta-defensin 2, which is located in this region, is amongst the
      most highly up-regulated proteins in lesional skin and has cytokine-like
      properties in addition to potent antimicrobial activity. Although several
      additional genes remain to be identified, the variants that have so far been
      described support the autoimmune basis of psoriasis indicating that the disease
      may be mediated by T-cells reacting against (self)antigen(s) in the binding
      pocket of HLA-C, with contribution from the recently described Th17 subset of T
      cells which are maintained by the IL-23 cytokine axis. These genetic variants
      together with pro-inflammatory environment caused by exaggerated antimicrobial
      response (beta-defensins) and dysregulation of signaling pathways (ubiquination),
      suggest the type of mechanism by which psoriasis can arise. Elucidation of the
      genetic basis of psoriasis and the underlying pathogenic mechanisms hold the
      potential for eventual cure of this enigmatic disorder.

PMID- 18833072
TI  - Cardiovascular morbidity in psoriasis: epidemiology, pathomechanisms, and
      clinical consequences.
AB  - Psoriasis is a common inflammatory skin condition. Around 25% of patients develop
      joint involvement in the form of psoriatic arthritis as well. Recent
      epidemiologic studies demonstrated an increased cardiovascular morbidity among
      psoriasis patients. Although the association of psoriasis with cardiovascular
      diseases such as hypertension, myocardial infarction, and heart failure, is now
      widely accepted, the pathogenetic link remains yet unclear. High prevalence of
      the metabolic syndrome as well as adverse effects of systemic anti-psoriatic
      therapies may contribute to the observed association. Several pilot studies
      suggest that insulin resistance may contribute to the development of
      cardiovascular diseases in psoriasis patients who exhibit metabolic parameters
      like patients developing diabetes. Retrospective data provide evidence that
      continuous systemic therapy may reduce the risk of cardiovascular mortality in
      psoriasis patients. The consequences for the management of psoriasis at this
      point are two-fold: as co-morbidity goes along with co-medication, potential drug
      interactions need to be kept in mind when choosing a systemic anti-psoriatic
      therapy. Moreover, as psoriasis itself is a risk factor for cardiovascular
      morbidity, patients must avoid other known risk factors such as obesity or
      smoking. Dermatologists need to communicate this additional risk to their
      patients and support them accordingly.

PMID- 18833073
TI  - Biological agents in the treatment of psoriasis.
AB  - Psoriasis is a chronic immune-mediated inflammatory disease, with an estimated
      prevalence of 1-3% worldwide. It is considered to be a multisystemic disorder,
      primarily affecting the skin and joints (psoriatic arthritis), and associated
      with other inflammatory conditions such as inflammatory bowel disease and
      coronary heart disease among others. Today, thanks to recent scientific advances
      that have allowed us to deepen our understanding of the pathogenesis of
      psoriasis, we count with an expanded therapeutic armamentarium that includes
      targeted therapy in the form of ''biologics''. These agents have gained
      popularity as safe, effective, and convenient alternatives for the treatment of
      chronic moderate to severe plaque psoriasis. This review will focus on the main
      biologics used in the treatment of moderate to severe plaque psoriasis:
      efalizumab, alefacept, etanercept, infliximab, adalimumab and the new Interleukin
      (IL) 12/23 inhibitors.

PMID- 18833074
TI  - 308 nm monochromatic excimer light in dermatology: personal experience and review
      of the literature.
AB  - RESULTS: For over five years, we have been using a new ultraviolet B ray source,
      a Xenon-Chloride lamp emitting non-coherent, monochromatic 308-nm light that
      represents the natural evolution of the excimer laser. A source of monochromatic
      excimer light (MEL) produces 50 mW/cm(2) power density at a distance of 15 cm
      from the source and has a maximum irradiating area of 504 cm(2), this feature
      representing the greatest therapeutic advantage offered by 308 nm sources. On the
      other hand, the benefits offered by the MEL compared to traditional
      phototherapies are essentially correlated to the fact that there is no need to
      administer oral psoralens (PUVA therapy) and that sessions need to be repeated
      only every 7-15 days, an important condition for the improvement of the patient's
      quality of life (since at least 2-3 weekly sessions are required with the
      traditional UVB therapy). Using MEL, UV B light can be applied on the entire
      body, with partial subintrant skin irradiations, or on one or just a few
      individual patches, taking care to accurately protect the healthy surrounding
      skin and allowing for a phototherapy exclusively targeted onto the lesion to be
      treated. Clinical indications and the reasons for choosing MEL for the treatment
      of photosensitive skin disorders are virtually identical to those stated for PUVA
      therapy or narrowband UV B light. Due to the absence of photosensitizing
      substances and drug-induced toxicity, patients who work in the open air, pregnant
      women and patients suffering from liver or kidney failure can also be treated.
      Furthermore, the short time required for sessions, the duration of cycles and the
      selective exposure of the skin areas to be treated undoubtedly represent
      significant benefits for patients in terms of safety and efficacy. In addition to
      psoriasis, the use of MEL can also be extended to other pathologies such as
      vitiligo, alopecia areata, atopic dermatitis and patch-stage IA mycosis fungoides
      with encouraging

PMID- 18833075
TI  - Diffuse skin spread of HIV-associated visceral leishmaniasis: cumbersome
      diagnostic and therapeutic issues.
AB  - An infrequent and atypical case report of HIV-associated visceral leishmaniasis
      complicated by a diffuse, aspecific maculo-papular cutaneous involvement was
      characterized by a prolonged course, and a lack of response to repeated
      attack/maintenance cycles performed with liposomal amphotericin B, despite a
      satisfactory immune response maintained thanks to a concurrent, potent
      combination antiretroviral treatment. Only a very prolonged administration of the
      older i.v. pentamidine isethionate together with oral paromomycin led to a slow,
      but complete cure of both visceral leishmaniasis and its related skin
      dissemination, in absence of adverse events and long-term disease relapses.

PMID- 18833076
TI  - Keratinocytic epidermal nevus with oral involvement and cleft palate.
AB  - Epidermal nevus syndromes are a heterogeneous group of genetic disorders
      characterized by the presence of an epidermal nevus with visceral involvement.
      Keratinocytic epidermal nevus syndromes are not a clear entity, but all the
      reported cases showed the presence of a keratinocytic epidermal nevus associated
      with different systemic lesions. In our report the keratinocytic epidermal nevus
      syndrome is defined by the presence of the nevus on the face, intraoral lesions
      and cleft palate in a 1-year-old girl.

PMID- 18833077
TI  - Videodermatoscopy enhances the diagnostic capability in a case of scabies of the
      scalp.

PMID- 18833078
TI  - Type 1 neurofibromatosis and the vitiligo.

PMID- 18833079
TI  - Immunohistochemical evaluation of toxic epidermal necrolysis treated with human
      intravenous immunoglobulin.
AB  - AIM: Toxic epidermal necrolysis (TEN) is a severe drug reaction characterized by
      massive epidermal cell death. The authors of the current study and others have
      noted improved outcomes in TEN patients treated with human intravenous
      immunoglobulin (IVIG), purportedly due to its ability to inhibit the fas/fas
      ligand (Fas-L) apoptotic pathway, but published case series evaluating TEN
      through the use of immunohistochemical antibody stains for Fas and Fas-L before
      and after IVIG treatment are lacking. The authors hypothesized that due to IVIG's
      ability to arrest the evolution of TEN, expression of Fas/Fas-L on keratinocytes
      would be decreased or absent following IVIG treatment. METHODS: Ten patients
      diagnosed with TEN underwent biopsies of their lesions prior to and five days
      after treatment with IVIG. Seven post-treatment biopsies were of sufficient
      quality to undergo evaluation. RESULTS: All ten pretreatment biopsies had Fas and
      Fas-L expression by immunohistochemistry, while six out of seven (85.7%) post
      treatment biopsies failed to demonstrate Fas or Fas-L expression. One of seven
      post-treatment biopsies stained positive for Fas and Fas-L. CONCLUSION: This
      reduced immunohistochemical expression of apoptotic markers may represent IVIG
      inhibition of the pathogenic mechanism of TEN. Alternatively reduced Fas and Fas
      L may be a feature of reepithelialization in TEN, or characteristic of rapidly
      proliferating epidermis.

PMID- 18833080
TI  - Dendritic cell vaccines in metastasized malignant melanoma.
AB  - Dendritic cells as immunotherapeutic agents against malignancies have been
      applied for over ten years. Proof of principle studies demonstrated
      immunogenicity of dendritic cells even in patients suffering from advanced
      malignancies. Clinicians and immunologists early focused on this innovative
      immunotherapeutic approach in metastasized malignant melanoma--a malignancy so
      far resisting most traditional oncologic treatment modalities. In this review we
      summarize the experience obtained of dendritic cell therapy in patients with
      malignant melanoma and state past, present and future obstacles. So far over 850
      melanoma patients in 51 trials have been reported since 1998. Within these trials
      there exists a vast heterogeneity concerning type of dendritic cell applied,
      differentiation and maturation of dendritic cells, type of antigen target and
      nature, application mode, number of cells applied, vaccination intervals in
      addition to patients treated at various stages of melanoma. A minority of
      patients developed anticipated autoimmune adverse events in addition to expected
      immune system activation symptoms such as fever and local site reaction. As only
      solitary World Health Organization (WHO) grade III or IV adverse events were
      reported one can state that dendritic cell therapy is safe. Objective clinical
      responses have repeatedly been observed in a minority of heavily pretreated and
      far advanced melanoma patients. Future challenges include optimization and
      standardization of dendritic cell generation and application, addition of
      synergistic immunomodulatory agents to enhance immunogenicity and block tumor
      escape and treatment of patients at earlier stages of disease who will benefit
      from this innovative therapy.

PMID- 18833081
TI  - Melanoma and pregnancy.
AB  - Herein we analyze three important issues concerning melanoma and pregnancy: 1)
      While initial case reports and case series predicted a grim prognosis for the
      woman diagnosed with melanoma during pregnancy, we summarize more recent
      controlled studies that suggest that pregnancy has no effect on survival in women
      diagnosed with localized cutaneous melanoma. 2) We review the prognosis for the
      fetus when a woman is diagnosed with melanoma during pregnancy. While melanoma is
      the most common malignancy to metastasize to the placenta, metastatic melanoma to
      the fetus appears to be a rare event. 3) How do we answer questions about future
      pregnancies and hormonal therapy when counseling women who have been diagnosed
      with melanoma during pregnancy or the childbearing years? Will future pregnancies
      worsen prognosis? Based on limited data, pregnancies subsequent to a diagnosis of
      localized melanoma do not appear to impact prognosis. Are oral contraceptive
      pills or hormonal replacement therapy contraindicated in these women? Strong
      epidemiologic evidence suggests that exposure to oral contraceptive pills do not
      increase the risk for melanoma. Although only a small number of studies have
      addressed the risk of hormone replacement therapy, the reports demonstrate that
      this also does not appear to enhance the risk for developing melanoma.

PMID- 18833082
TI  - Impact of prophylactic human papillomavirus vaccines on dermatology and
      venereology.
AB  - Prophylactic HPV L1 VLP quadrivalent and bivalent vaccines have a great
      importance for patients seen by dermatologists and venereologists. Both vaccines
      protect against HPV16- and HPV 18-associated anogenital cancers, as well as
      cancers of the mouth, the upper respiratory tract and skin, especially of the
      fingers and periungual region. The quadrivalent HPV6, 11, 16, 18 vaccine also
      prevents anogenital warts (condylomata acuminata) which are the most common
      benign tumors of this body region. HPV-vaccination (Gardasil) has been approved
      in Germany and other European Countries since October 2006 for young girls
      between 9-16 and young women between 16-26 years of age. Many experts feel that
      boys and young men should also be vaccinated. Men would profit from a vaccine
      that protects against HPV infections, especially anogenital warts, as well as
      penile and anal carcinomas. In immunosuppressed organ transplant recipients and
      HIV-positive patients. HPV disease can be widespread, chronic and often may
      rapidly progress to malignant tumors. Thus, these individuals would greatly
      benefit from prophylactic HPV immunization.

PMID- 18833083
TI  - A case of Klippel-Trenaunay syndrome involving only upper limbs.
AB  - The case of a 14-year-old girl suffering from Klippel-Trenaunay syndrome
      associated with multiple port-wine stain type vascular anomalies and varicose
      veins involving upper limbs is described. Finger deformations are common in
      Klippel-Trenaunay syndrome. In our patient, striking hypertrophy of soft tissues
      and overgrowth of bones were observed on both forearms and finger deformations
      were observed particularly on right thumb and index finger. Although lower limb
      involvement is very common amongst the patients with Klippel-Trenaunay syndrome,
      in our patient involvement of the lower limbs was not observed.

PMID- 18833084
TI  - Acute juvenile pityriasis rubra pilaris: a case report after mononucleosis
      infection.
AB  - A 24-year-old male boy presented dermatosis which first appeared acutely after an
      infection at age 17. Clinical and histopathologic examinations were consistent
      with a diagnosis of juvenile pityriasis rubra pilaris type III. Treatment with
      UVB narrow-band led to complete resolution of the dermatitis within 1 year.
      Pityriasis rubra pilaris is a papulosquamous disorder of unknown etiology, which
      can be treated with retinoids, methotrexate, cyclosporine, and narrow-band
      phototherapy.

PMID- 18833085
TI  - The arthropatic psoriasis and the Klinefelter's syndrome.

PMID- 18833086
TI  - [Dynamics of acoustic function maturation in premature neonates according to
      evoked distortion product otoacoustic emission].
AB  - Audiological screening by registration of delayed evoked distortion product
      otoacoustic emission (DPOE) was made in 148 premature neonates (296 ears) born at
      gestation week 24-37. All the examinees were divided into three groups depending
      on the gestation term and were followed up for the first year of life. The
      results of the screening tests with reference to postconceptional and real age of
      premature infants are given. Recommendations are available on wide audiological
      examinations of premature infants depending on their gestational and
      postconceptional age.

PMID- 18833087
TI  - [Distribution of main EEG rhythms in patients with initial neurosensory hearing
      disorders of vascular genesis].
AB  - Forty patients with neurosensory hearing disorders of vascular genesis were
      examined and divided into two groups. Patients with tone hearing disorders in
      conventional (0.125-8 kHz) and extended (9-16 kHz) frequency ranges entered group
      1, those with such disorders in the extended range--group 2. Patients of group 1
      had more pronounced cardiovascular dysfunction. Control group consisted of 15
      persons with normal hearing. Electroencephalography (EEG) has shown that initial
      neurosensory hearing disorders were accompanied with redistribution of the main
      EEG rhythms especially in group 1. Compared to controls, these patients
      demonstrated significantly (p<0.05) reduced representation of alpha-rhythm while
      that of beta-activity rose showing involvement of cerebral cortical structures.
      Adequate preventive measures in patients with initial neurosensory hearing
      disorders of vascular genesis are able to protect such patients against
      development of neurosensory hypoacusis of vascular genesis.

PMID- 18833088
TI  - [Objective assessment of hearing in neonates by registration of brain stem evoked
      potentials].
AB  - A detailed analysis of the findings of registration of short-latent evoked
      acoustic potentials (SLEP) in neonates with symptoms of ante- and postnatal
      affection of the central nervous system (CNS) and in healthy children has shown
      that some SLEP parameters (latent periods, interpeak intervals) in neonates with
      impaired CNS and healthy infants differ.

PMID- 18833089
TI  - [Occupational hypoacusis in transport workers].
AB  - The article concerns prevalence and causes of occupational neurosensory
      hypoacusis (ONH) in transport workers exposed to intensive industrial noise. Most
      often ONH is diagnosed in civil aviation air crews and railway locomotive crews
      aged 45-50 years with service history 15 years and longer. Because ONH morbidity
      has a trend to rise, it is necessary to update medical criteria of professional
      fitness and rules of medical examination of transport workers, especially those
      engaged in safety control. International classifications and scientific
      approaches may be considered. Innovations in noise reduction, modern hearing
      protection measures, early diagnosis and rehabilitation must be promoted.

PMID- 18833090
TI  - [ECG parameters in initial neurosensory hypoacusis in early hypertension].
AB  - ECG and audiometry parameters were studied in conventional (0.125-8 kHz) and
      extended (9-16 kHz) frequency range in 115 patients with early neurosensory
      hypoacusis (NSH) in combination with initial hypertension or episodes of blood
      pressure rise. The patients were divided into two groups: group 1 (n=60)
      consisted of hypertensive patients with NSH, group 2--of NSH patients with
      episodes of high blood pressure. Tone hearing indices in groups 1 and 2 differed
      more in extended frequency range (9-16 kHz), especially in frequencies 14 and 16
      kHz. As shown by ECG, group 1 patients exhibited more severe hypoxic myocardial
      changes. The conclusion is that early NSH patients with initial hypertension or
      episodes of high blood pressure are recommended to undergo ECG for administration
      of more effective treatment.

PMID- 18833091
TI  - [Diagnosis of labyrinthine fistula in patients suffering from otitis media
      purulenta chronica with cholesteatoma: informative value of different methods].
AB  - Informative content of different methods of labyrinthine fistulas (LF) diagnosis
      was assessed in 118 patients suffering from otitis media purulenta chronica
      (OMPC) with cholesteatoma which ran for 20 years and longer in 82.2% patients,
      83.9% had fistula symptom. Unilateral hypoacusis was diagnosed in 68 (57.6%),
      bilateral--in 50 (42.4%) patients. Severity of vestibular disorders correlated
      positively with LF size and duration of the disease. Advanced LF was detected in
      65 (55.1%) patients, multiple--in 7 (5.9%). Computed tomography of the temporal
      bone detected LF in all 29 OMPC examinees including "silent" fistulas. Thus, the
      disease history, clinically manifest fistula symptom and CT of the temporal bone
      are most informative for diagnosis of LF in OMPC with cholesteatoma.

PMID- 18833092
TI  - [Efficacy of remote gamma-therapy in patients with juvenile angiofibroma of the
      base of the skull].
AB  - The results of radiation therapy of 48 patients with juvenile nasopharyngeal
      angiofibroma were analysed. It was found that radiation therapy can produce 80%
      stable remissions in postoperative recurrence or unresectable tumor. The response
      did not depend on primary size of the tumor and was better in a total dose over
      35 Gy and in children over 14 years of age. Long-term side effects were minimal
      and did not deteriorate quality of life.

PMID- 18833093
TI  - [Therapeutic and diagnostic criteria of choice of treatment methods in adenoid
      vegetations as a focus of chronic infection in childhood].
AB  - Clinical, laboratory and device methods were used in examinations of 175
      children. Basing on the results of the above examinations, therapeutic and
      diagnostic criteria of choice of a method of treating adenoid vegetations in
      children were proposed.

PMID- 18833094
TI  - [The role of bacteriological examination in diagnosis of chronic tonsillitis].
AB  - A bacteriological examination was made in 105 patients with various forms of
      chronic tonsillitis. Eighteen cultures of beta-hemolytic streptococcus (BHSA)
      were isolated from 36 patients with paratonsillar abscesses. BHSA seeding in
      paratonsillar abscess was 50.0%. Eight BHSA cultures were isolated from 69
      patients with chronic tonsillitis. BHSA seeding in chronic tonsillitis was 11.6%.
      Adequate set of culture media for BHSA growth was optimized. The technique of the
      sample collection from tonsillar lacunes was improved. The significance of
      bacteriological diagnosis of chronic tonsillitis increases considerably due to
      optimization of out- and intralaboratory tests at the preanalytic stage of the
      study.

PMID- 18833095
TI  - [Involvement of bacterial microflora in etiopathogenesis of chronic sinusitis].
AB  - We used the method of amplification of RNA 16S genes in combination with
      discriminating hybridization of amplification products with species-specific
      probes in DNA-chip format to identify bacterial flora in patients with chronic
      sinusitis. A total of 34 samples from 33 patients suffering from chronic
      sinusitis have been tested. Biopsy specimens of sinus mucosa served as material
      for sinus microflora studies in the absence of sinusitis exacerbation. It was
      found that in the exacerbation-free period the samples contained no bacterial RNA
      16S while human RNA was isolated from all the samples. Moreover, we isolated and
      typed fragments of 16S RNA E.fecalis genes from tested in parallel sample of the
      wall of the oroantral fistula. This confirmed significance and effectiveness of
      the above method. We came to the conclusion that sinus mucosa is sterile in
      chronic hyperplastic sinusitis.

PMID- 18833096
TI  - [An original technique of determination of the form and fixation of septal
      stents].
AB  - The authors consider the problems of fixation of the operated nasal septum, show
      shortcomings of present-day oval septal stents and technique of stent fixation,
      for the first time describe vector CT-anatomy of the zone of surgical
      intervention on the nasal septum basing on 67 computer reformations of the nasal
      septum and lateral nasal wall, propose optimal shape of the intranasal stent and
      a reliable technique of septal stent fixation to the nasal septum. The analysis
      of stenting of the nasal septum in 42 patients after septoplasty has shown that
      an original stent and a method of its fixation completely meet the requirements
      for septal stents.

PMID- 18833097
TI  - [Septal stents--a perspective tamponadeless management of patients after
      septoplasty].
AB  - The article deals with pathophysiology of disturbed nasal breathing, tools of
      surgical correction of deviated nasal septum, features of the course of wound
      process. Clinical efficacy of stent fixation of the septum and conventional
      elastic tamponade was compared in 38 patients who had undergone septoplasty and
      submucous radiowave disintegration of the lower nasal turbinate bones for
      deviation of the nasal septum and a neurovegetative form of chronic vasomotor
      rhinitis. Higher efficacy of intranasal stenting is shown. Tamponadeless
      management of the patients after surgical interevention on the nasal septum is
      demonstrated.

PMID- 18833098
TI  - [Collagen plate Tachokomb in plastic surgery on paranasal sinus anterior walls].
AB  - ENT clinic of the Altai State Medical University has the experience with
      extranasal-endonasal use of a collagen plate Tachocomb in 150 patients with
      chronic sinusitis; 35 patients, of them 2 patients with osteoma of the frontal
      sinus, have undergone plastic reconstruction of the anterior walls of the frontal
      and maxillary sinus with the plate Tachocapital KA, Cyrillicomb. Follow-up of the
      patients demonstrated efficacy of this method, absence of complications and
      postoperative recurrences.

PMID- 18833099
TI  - [Inhalation therapy of laryngeal inflammation].
AB  - Inhalation therapy is a highly effective method of local anti-inflammatory
      therapy in combined treatment of anti-inflammatory laryngeal diseases. Schemes of
      inhalation therapy in different laryngeal diseases are presented basing on the
      experience with examination and treatment of 140 patients.

PMID- 18833100
TI  - [Clinical characteristic of schizoaffective disorders developed after psychic
      trauma].
AB  - Seventy-four patients with schizoaffective disorder caused by psychic trauma (a
      basic group) and 51 patients with spontaneous manifestation of this disorder (a
      comparison group) have been studied. The prevalence of personality traits of
      inhibited spectrum with predisposition to affective disorders and psychogenic
      reactions were observed in the patients of the basic group. Situations of
      emotional deprivation were the most frequent content of mental stress. The
      psychic trauma exerts a provoking, pathoplastic and pathokinetic effect in
      schizoaffective disorder. Three variants of the course of schizoaffective
      disorder after emotional stress have been singled out: with psychogenic neurotic
      manifestation, with psychogenic psychotic manifestation (psychogenic reactive
      depression type) and with endogenous manifestation.

PMID- 18833101
TI  - [Neuroimmunological aspects of the pathogenesis of Tourette syndrome and use of
      immunoglobulins in the treatment of children].
AB  - Sixty children, aged from 6 to 16 years, with tics and Tourette syndrome have
      been studied. Western immunoblotting techniques has been used to evaluate the
      serum antibodies against the caudate nucleus. These antibodies have been detected
      in 10 cases. Seven patients with Tourette syndrome who were treated with
      neuroleptics for a long time without any therapeutical effect received the
      immunomodulatory therapy with intravenous immunoglobulin. The regression of motor
      and vocal tics as well as improvement of behavioral symptoms were observed
      (duration of remission was more than 6 months). These findings and successful
      immunomodulatory therapy of patients with Tourette syndrome confirm previous
      reports in the literature and support the idea of immunologically triggered
      disturbance of the striatal dopaminergic system.

PMID- 18833102
TI  - [Comparative efficacy of different muscle relaxants in the rehabilitation of post
      stroke patients with spasticity].
AB  - An influence of different muscle relaxants on muscle tone and functional
      rehabilitation has been studied in 360 post-stroke patients. Muscle tone has been
      assessed with the Ashworth scale and functional rehabilitation with Barthel,
      Lindmark and Scandinavian scales as well as the Merton & Sutton scale. Efficacy
      of muscle relaxants has been assessed by the 2 min. walking test. Moreover, we
      suggested a coefficient for calculating drug efficacy. The results of the study
      revealed that tolperisone was the most efficient in the treatment of post-stroke
      patients with spasticity. Tizanidine was also effective but to a lesser extent.
      Other drugs studied did not reveal any significant effect. Tolperisone had a good
      tolerability, the adverse effects in patients treated with this drug were
      registered more rarely compared to other ones.

PMID- 18833103
TI  - [Actovegin in the treatment of brain injuries of mild and moderate severity].
AB  - Sixty-eight patients, including 32 patients of the main group who received
      aktovegin in addition to standard therapy and 36 patients of the control group
      with standard therapy only, have been studied. In both groups, various traumatic
      injuries (small focal injuries, subdural and epidural hematomas, traumatic
      subarachnoid hemorrhages, a combination of covering hematoma and small focal
      injuries) have been found. Aktovegin has been used in drops in dosage 400 mg per
      200 ml physiological solution for 10 days. A comparative analysis of clinical
      data and results of instrumental studies (EEG, CT etc) in the main and control
      groups gives grounds to conclude that the use of aktovegin in the complex with
      standard therapy improves the course of brain injuries thus promoting the earlier
      compensation of disturbed functions and shortening the terms of treatment. The
      regress of asthenic symptoms as well as positive EEG changes are most pronounced.

PMID- 18833104
TI  - [The therapeutic potential of cerebrolysin in the preventive therapy of
      Alzheimer's disease].
AB  - A potential of prolonged 2-years course of cerebrolysin therapy with courses
      repeated every 6 months to slow down or prevent the transition of the syndrome of
      mild cognitive impairment, amnestic type, to clinically relevant dementia has
      been studied in the open comparative study of 73 patients divided into 2 groups,
      one of which included patients treated with cerebrolysin and another one those
      who did not receive this drug. The effect of the 2-years course therapy with
      cerebrolysin suggested by the authors has been proven. Such therapy allows to
      prevent the progression of cognitive deficit and development of dementia of
      Alzheimer's type. The results obtained give grounds to recommend this course
      therapy for prevention of dementia in elderly patients with mild cognitive
      impairment.

PMID- 18833105
TI  - [The study of therapeutic efficacy of two forms of risperidone--rileptid and
      rispolept in patients with schizophrenia].
AB  - Generic drugs represent a big part of the Russian pharmaceutical market, a number
      of registered copies of the same drug manufactured by different pharmaceutical
      companies being estimated as several tens of drugs that does not mean their
      equally high quality and complete interchangeability. A choice of optimal price
      to-quality ratio of a drug among a great number of analogues is possible only
      with taking into account a number of factors related to a manufacturer, a drug
      and a patient. The most important index of interchangeability of generic drugs is
      their therapeutic equivalence to the original one. A study aimed to compare the
      therapeutic equivalence of two preparations of risperidone--original rispolept
      and generic rileptid--has been carried out. The comparison of efficacy and
      tolerability of the therapy has not revealed differences both in any of the
      parameters and in any stages of the study. In conclusion, the full therapeutic
      equivalence of generic drug rileptid to original rispolept is revealed.

PMID- 18833106
TI  - [A comparative study of efficacy and safety of torin and zoloft].
AB  - Zoloft (sertraline) is an original antidepressant of "Pfizer", torin is a generic
      form of sertraline of Veropharm. An aim of the study was to compare clinical
      effectiveness and tolerability of original and generic drugs. Forty patients with
      moderate and severe depression without psychotic symptoms have been studied: 20
      of them were treated with torin and 20 with zoloft. Patient's state has been
      assessed during 7 weeks (1 week--wash out and 6 week--active therapy) clinically
      and using the Hamilton and CGI scales on 7th, 14th, 21st, 28th and 42nd days. The
      clinical equivalence of torin and the original drug demonstrated. Torin had a
      distinct thymoanaleptic effect, the primary action of which addresses anxious
      affect. This drug was soft as well as zoloft.

PMID- 18833107
TI  - [Brain evoked potentials as correlates of neural dysfunction in the myofascial
      pain syndrome].
AB  - To study the peculiarities of nervous system functioning in the conditions of
      nociceptive afferentation from myofascial trigger points in the myofascial pain
      syndrome (MFPS), 130 patients, 57 men and 73 women, aged from 20 to 55 years,
      have been examined. A method of somatosensory evoked potentials (SSEP) with
      recording of amplitudes and latencies of their main components has been used. Two
      relevant conclusions based on the results of the study have been made: 1) the
      similar parameters of SSEP components before and after stopping the MFPS have a
      different neurophysiologic basis; 2) during the treatment, several variants of
      changes of SSEP parameters reflecting the interaction of different
      neurophysiological mechanisms can be found.

PMID- 18833108
TI  - [Cognitive evoked potentials in panic disorders].
AB  - Sixteen healthy people and 79 patients with panic disorders (PD), including 50
      patients with neurosis (ICD-10 F40-41), 18 with personality disorder (F60) and 11
      with schizotypal disorder (F21) have been studied. The main investigation method
      is recording of cognitive evoked potentials (P300 parameters). Mental and
      neuropsychological status of patients has been assessed as well. Despite the
      common clinical presentations of PD, peculiarities of evoked potentials
      reflecting sensory, activation and cognitive processes in different group of
      patients are revealed. The reduction of activation processes is observed in
      patients with neurosis and personality disorder combined with emotional
      instability in the latter ones. The increase of latency in response to non-target
      stimuli (a sensory component) is shown in schizotypal patients, the latter may be
      related to the decrease of activation of frontal-central brain areas.

PMID- 18833109
TI  - [Pathology of oligodendroglia and myelinated fibers of the hippocampus in
      schizophrenia (an ultrastructural and morphometric study)].
AB  - The authors studied the ultrastructure of oligodendroglia and myelinated fibers
      and assessed quantitatively their density and proportion of pathologically
      changed myelinated fibers in the CA3 region of the hippocampus in 25 cases with
      schizophrenia and 25 control cases without mental pathology. Dystrophic changes
      of oligodendrocytes structure and an atrophy of part of myelinated fibers were
      found in schizophrenia. The severity of pathology was significantly associated
      with the age at disease onset. The neuropathological changes proved to be related
      with the reactivity of microglia that suggests a role of immune factors in the
      pathogenesis of disturbances observed in the study.

PMID- 18833110
TI  - [Changes of the level of serum antibodies to neuroantigens in patients with
      schizophrenia during the treatment].
AB  - The level of antibodies (AT) to neuroantigens (nerve growth factor and basic
      myelin protein) has been studied in the serum of 80 patients with schizophrenia,
      attack-like type, (ICD-10 items F20.01-02) during the treatment with psychotropic
      drugs. Therapeutic effectiveness has been measured clinically and with the PANSS.
      It has been shown that the autoimmune component is present during the acute
      episode of schizophrenia in about 30% of cases. No statistically significant
      differences have been found in the mean values of AT before and after the
      treatment however the dynamics of their changes has been closely related with the
      results of therapy: the decrease of AT level during the therapy is a predictive
      factor for good therapeutical remission; on the contrary, the increase of this
      level may be considered as an unfavorable prognostic factor.

PMID- 18833111
TI  - [Changes in the relationship between cognitive functioning and psychopathological
      symptoms in patients with paranoid schizophrenia in the periods of psychosis and
      development of remission].
AB  - The aim of our study was to investigate the relationship between cognitive
      functioning and psychopathological symptoms in patients with paranoid
      schizophrenia both in acute state and in the period of development of remission.
      Fourteen patients with paranoid schizophrenia (ICD-10, F20.0) were examined twice
      during 4,5-5 months, first--at the acute episode and second--at the period of
      development of remission during the treatment with olanzapine. The PANSS for
      assessment of psychopathological symptoms and Wechsler Adult Intelligence Scale
      (WAIS) and Benton Visual Retention Test as measures of cognitive functioning have
      been used. Though the patient's general cognitive functioning was in a normal
      range. The results of performance part (vs. verbal part) of the WAIS were
      significantly lower. The performance subtests idem were more sensible for
      changing in patient's actual status. The reduction of psychotic symptoms was
      accompanied by the improvement of almost all cognitive domains studied. The
      spectrum of interrelations between different aspects of cognition and clinical
      symptoms was revealed. These interrelations vary greatly in depending of the
      state of patients (exacerbation of psychosis or remission). During the remission,
      patient's cognitive functioning negatively correlated with two types of
      disorders: residual hallucinations and disturbance of verbal communication.

PMID- 18833112
TI  - [Evaluation of factors influencing the recovery of cognitive functions during the
      early stage of rehabilitation in subjects with traumatic brain injury].
AB  - An objective of the study was to specify the factors influencing the recovery of
      cognitive functions in subjects with moderate or severe traumatic brain injury
      (TBI) in the early stage of rehabilitation. One hundred and thirty-one patients
      with moderate or severe TBI have been studied. The early rehabilitation comprised
      two phases: acute and subacute. Cognitive dysfunction and its recovery at the end
      of early rehabilitation as well as efficacy of rehabilitation have been assessed
      using the Functional Independence Measure. According to this test, patients were
      assigned into 3 groups: high efficacy, moderate efficacy and no significant
      efficacy of rehabilitation. Subjects with moderate or severe TBI had significant
      cognitive dysfunction at the beginning of the acute period of TBI: these patients
      required maximum assistance in understanding and memorizing of the tasks. The
      assessment of cognitive functions at the end of early rehabilitation revealed
      that most of patients with moderate or severe TBI were independent, although they
      still needed assistance to understand, memorize and express their thoughts, and
      some patients required minimum assistance in the actions related to cognitive
      functions. The assessment of recovery of cognitive functions at this period
      showed that 41,3% of patients performed independently the actions related to
      cognitive functions, 17,5% could perform in the presence of other people, 41,3%
      needed help from others. Speech and perceptions disorders, sleep disorders, brain
      injury localized in the temporal areas were significantly associated (p<0,05)
      with low efficacy of rehabilitation.

PMID- 18833113
TI  - [Mechanisms of formation of chronic low back pain relapse and their correction in
      patients with dorsopathy].
AB  - A clinical-neurological, psychological, biochemical and electromyographic study
      of 40 operated and 40 non-operated patients with chronic low back pain syndrome
      was conducted before and after treatment. The authors used various modes of
      administration of xydifonum, a chelate from the group of bisphosphonates,
      including electrophoretic, peroral and administration in the form of ointment,
      administered in turn with heparin one to improve the antiplatelet effect, using
      photopheresis the with the help of the state-of-the art photomatrix LED
      equipment. The application of Ca2+-modulating properties of xydifonum demonstrate
      its universality in achieving of analgesic, muscle-relaxing, anxiolytic and
      antidepressant effects thus allowing to exclude polypragmasy. This is a main
      difference between this drug and other medications with limited effects. Based on
      the results obtained, the authors propose a scheme of development of chronic low
      back pain.

PMID- 18833114
TI  - [The use of dipyridamole (curantyl) in combination with alpha-lipoic acid in the
      treatment of diabetic neuropathy with retinopathy].
AB  - Fifty-four patients diagnosed with distal sensomotor diabetic polyneuropathy of
      low extremities have been studied. All patients suffered from diabetes mellitus
      type 2 and had signs of retinopathy. It has been shown that berlition in dosage
      300 mg twice daily for 3 months exerts a significant positive effect on the state
      of sensory and motor functions as well as neurophysiologic disturbances. The
      effect is increased significantly, especially in the sensory sphere (tactile,
      temperature and pain sensitivity), when the drug is used in combination with
      curantyl in dosage 50 mg twice daily for 3 months. The positive influence of this
      combination on the development of retinopathy is also observed.

PMID- 18833115
TI  - [The clinical-pharmacoeconomic study of efficacy of stalevo in the treatment of
      Parkinson's disease with motor fluctuations].
AB  - An open randomized study of pharmacoeconomic efficacy of stalevo in patients with
      Parkinson's disease with motor fluctuations was conducted. The results of the
      study revealed that the drug substantially reduced motor deficit, increased the
      "on"-period, decreased the duration and severity of the "off" period, improved
      the daily activity and quality of life of patients compared to standard therapy
      with an additional dosage of levodopa/DDC inhibitor. Despite the increase in
      cost, the use of stalevo in the treatment of Parkinson's disease with motor
      fluctuations is cost-effective in long-term (already after two years) management
      of patients.

PMID- 18833116
TI  - [The treatment of Alzheimer's disease in patients with comorbid somatic
      pathology].
AB  - To study efficacy and safety of cholinergic therapy in patients with Alzheimer's
      disease or combined Alzheimer's and vascular dementia and marked somatic
      pathology, 30 patients, aged from 54-85 years, with mild or moderate dementia
      have been studied. Patients were treated with rivastigmine (exelon) in dosage 3
      12 mg daily during 3 months. The safety of the drug for patients with comorbid
      somatic pathology has been shown: during the treatment no severe aversive effects
      or strengthening of diseases of visceral organs were observed. The improvement of
      global clinical state as well as reduction of cognitive and behavioral disorders
      indicate the high effectiveness of exelon. The recommendations allowing to
      improve the tolerability of treatment with exelon of patients with comorbid
      pathology of visceral organs are worked out.

PMID- 18833117
TI  - [Atomoxetine and piracetam in the treatment of attention deficit hyperactivity
      disorder in children].
AB  - Therapeutic effect of atomoxetine and piracetam has been assessed in the open
      controlled study included 42 patients with attention deficit hyperactivity
      disorder (ADHD), aged from 6 to 13 years. Group 1 (16 patients) received
      atomoxetine (strattera) in daily dosage 0,8-1,2 mg/kg as a monotherapy for 6
      weeks. Patients of group 2 (14 children) received piracetam as a monotherapy in
      daily dosage 50-70 mg/kg for 6 weeks. No pharmacological therapy was conducted in
      group 3 (a control one) which included 12 patients with ADHD. The high
      effectiveness of both atomoxetine and piracetam has been shown. However,
      comparing to piracetam, the therapeutic effect of atomoxetine was reached earlier
      (two weeks after the beginning of therapy) and was more pronounced for all
      components of syndromes.

PMID- 18833118
TI  - [The electroneuromyographic study of the radial nerve: compressive ischemic
      neuropathy of the posterior interosseous nerve].
AB  - The electroneuromyographic study of the posterior interosseous nerve (PIN) with
      determination of conduction block (CB) at the level of the upper third of the
      forearm using the surface electrodes has been carried out. Seven healthy
      volunteers, 22 patients with compressive-ischemic neuropathy (CIN) at the level
      of the supinator, 14 patients with the total affection of the radical nerve, aged
      from 21 to 64 years, have been studied. The M-response has been recorded from the
      extensor digitorum communis. Stimulation has been performed at: (1) the middle of
      the forearm; (2) the lateral brachium; (3) the axillary crease; (4) the Erb's
      point; (5) the sulcus of ulnar nerve; (6) the cubital flexion; (7) the inner part
      of the shoulder. A method of stepwise stimulation has been used in the segment "a
      middle third of the forearm--a middle third of the shoulder". The M-responses of
      similar shape and amplitude have been recorded by stimulation of the first and
      second points in the controls. The M-responses recorded by stimulation of the
      brachial plexus were higher by average of 44,2% compared to the radical nerve in
      the shoulder area. The focal CB was found between two stimulation points in 86,4%
      of patients with PIN CIN that was confirmed by the method of stepwise nerve
      stimulation as well. The correlation between CB and the data of the global
      electromyogram was revealed. In patients with the total affection of the radical
      nerve, the M-responses during stimulation of distal and proximal PIN points were
      absent and the similar M-responses were recorded by stimulation of the brachial
      plexus (the Erb's point and the axillary crease) as well as the inner part of the
      shoulder.

PMID- 18833119
TI  - [A state of hemostasis in patients with arterial hypertension complicated with
      early forms of chronic cerebrovascular pathology].
AB  - A complex investigation of hemostasis in 199 able-body men, mean age 48,6+/-0,6
      years, with arterial hypertension complicated with early forms of chronic
      cerebrovascular pathology, including the initial manifestations of cerebral blood
      supply insufficiency and discirculatory encephalopathy of stage I, has been
      carried out. The marked alterations of coagulation and anticoagulation mechanisms
      in patients with arterial hypertension of stage III with and without
      cerebrovascular complications have been revealed. The changes of both mechanisms
      are detected already at stages I and II of arterial hypertension with initial
      manifestations of cerebral blood and discirculatory encephalopathy of stage I.
      These results confirm the necessity for the correction of dysfunction of
      hemostasis immediately after diagnosis.

PMID- 18833120
TI  - [Basic principles of immunocorrective therapy in otorhinolaryngology].
AB  - The structural and functional basis of ENT mucosa immunity, leading methods of
      local immunity assessment in ENT pathology are presented. The experience of the
      chair and clinic of I.P. Pavlov St-Petersburg State Medical University in the
      field of immunotropic therapy of ENT pathology is reviewed.

PMID- 18833121
TI  - [Innovations in pathogenetic therapy for peripheral affection of the cranial
      nerves in otorhinolaryngology].
AB  - A total of 150 patients with peripheral affection of the facialnerve, 100
      patients with acute neurosensory hypoacusis, 50 patients with affection of the
      reciprocal nerve were treated by the method using reciprocal interaction between
      M- and H-cholinergic mechanisms. Treatment outcomes showed that
      anticholinesterase therapy raises the efficacy of rehabilitation in patients with
      peripheral affection of the cranial nerves.

PMID- 18833122
TI  - [Epstein-Barr virus infection as etiological and pathogenetic factor of exudative
      otitis media in childhood].
AB  - A detailed examination of 40 children with recurrent exudative otitis media (EOM)
      using enzyme immunoassay and polymerase chain reaction suggested that ENT
      pathology in the above children (EOM, adenoiditis, tonsillopharyngitis,
      sinusitis) may be a complication of acute or chronic Epstein-Barr virus infection
      (EBVI) because primary EBVI infection or its long-term persistence followed
      secondary immunodeficiency resulting in lymphoid system impairment and damage of
      upper airway epithelium. This causes a recurrent and persistent course of EOM.
      Etiotropic and pathogenetically sound treatment of children with recurrent EOM
      includes antiviral therapy, immunocorrection, rehabilitation with participation
      of pediatrician, immunologist, infection therapist.

PMID- 18833123
TI  - [How to raise efficacy of myringoplasty in extensive defects].
AB  - A comparative trial of miringoplasty efficacy with or without application of
      biosynthetic wound cover Biocom-1 was performed in 82 patients with sub- and
      total chronic defects or acute traumatic rupture of the tympanic membrane (58 and
      24 patients, respectively). Better clinico-morphological and functional results
      were achieved in patients treated with application of Biocom-1 (p<0.05). Their
      stay in hospital was also shorter. Biocom-1 not only provides stable position of
      the neotympanic membrane but also protects against secondary infection.

PMID- 18833124
TI  - [Efficacy of local use of recombinant interferon alpha-2 preparations in combined
      treatment of recurrent respiratory papillomatosis].
AB  - Clinical-immunological examination of 41 patients with recurrent respiratory
      papillomatosis (RRP) included determination of phenotype CD3, CD4, CD8, CD16,
      CD25, CD56, HLA-DR in peripheral blood by flow cytofluorimetry, the levels of IFN
      gamma, TNF-alpha, GM-CSF, IL-2, IL-4, IL-5, IL-10, IL-12, IL-13 in the laryngeal
      secretion by multiplex immunoassay. Interferon inhalation therapy was conducted
      to prevent recurrence in 23 patients after surgical treatment and in 18 patients
      as monotherapy. The efficacy of the monotherapy was 45.5%. Treatment with IFN
      alpha raised the levels of cytokines modulating an immune response by Th1-type
      (IFN-gamma, IL-12, IL-2) and GM-CSF, and reduced the levels of IL-4, IL-10 and IL
      13. Local treatment with recombinant IFN-alpha is effective in aggressive RRP. As
      prognostic markers of the treatment efficacy may serve baseline high levels of
      TNF-alpha and IL-4/IFN-gamma index in laryngeal secretion. Treatment efficacy can
      be assessed by raise of IFN-gamma, IL-2 and IL-12 in combination with reduction
      of IL-4/IFN-gamma index.

PMID- 18833125
TI  - [The technique of laser-induced interstitial thermotherapy in surgical treatment
      of respiratory papillomatosis].
AB  - Laser-induced interstitial thermotherapy (LITT) has been widely practiced in
      medicine for more than 20 years because of its advantages: local exposure,
      controllability, destruction of deep lesions, reliable hemostasis, wide range of
      biological effects, good tolerability, painlessness, absence of serious
      complications in valid performance. Otorhinolaryngologists from ENT clinic of
      I.P. Pavlov St-Petersburg Medical Academy have validated and used this method for
      removal of papillomas of the upper respiratory tract.

PMID- 18833126
TI  - [Some aspects of rhinoseptoplasty].
AB  - The article contents analysis of preoperative preparation of 34 patients for
      rhinoseptoplasty, points out most frequent short- and long-term complications,
      methods of complications prevention and management. It is recommended to use
      computed imaging and endoscopy for examination of patients with nasal
      deformation. Psychological status of the patient should be examined not only by
      the surgeon but also by the psychologist and psychiatrist.

PMID- 18833127
TI  - [Clinico-audiometric assessment of treatment outcomes in otosclerosis patients].
AB  - The review of 7-year experience in surgical treatment of otosclerosis provides
      the data on examination and intraoperative findings in 280 patients aged from 18
      to 62 years with the disease history 2-30 years. Excellent and good postoperative
      functional results were achieved in 93.2% cases.

PMID- 18833128
TI  - [Haloinhalation therapy of patients with allergic and vasomotor rhinitis].
AB  - The results of placebo-controlled randomized trial of effectiveness of
      haloinhalation treatment with application of individual inhaler Haloneb in 125
      patients with allergic and vasomotor rhinitis demonstrated high efficacy of the
      method. A positive effect was achieved in 90.4% patients with allergic and 92.1%
      with vasomotor rhinitis. Efficacy of the method is explained by anti-edema, anti
      allergic and anti-inflammatory effects of haloinhalation therapy.

PMID- 18833129
TI  - [Histamine releasing and immunomodulating activity of dental restorative
      materials].
AB  - Histamine releasing and immunomodulating activity of the following dental
      restorative materials (DRM) - Prizmafil, Filtek Z250, XRV Herculite Prodigy,
      Glasiosite, Te-Econol, Valux Plus, Polofil Supra were studied. It was shown that
      DRM under study as a rule did not possess the ability to release histamine (H)
      from human blood basophile (BB) excluding Filtek Z250 which release H from BB in
      patients with allergy and sound donors. The studied DRM implanted under mouse
      skin were able to modulate immune response to the allergen, at that some of them
      increased antibodies of IgE-class forming and other suppressed immune response
      caused by IgG-antibody forming. Received data have certain significance in the
      scheme of safety evaluation and individual assessment of DRM having acceptable
      biocompatibility for specific patient.

PMID- 18833130
TI  - [Biocompatibility study of some adhesive systems for tooth pulp indirect and
      direct capping].
AB  - Microcolorimetric method was used for study of toxic and antiproliferous
      properties of 3 adhesive systems acting by adhesive upon fibroblast cell culture.
      It was established that I Bond adhesive system was most biocompatible and that it
      can be used for direct and indirect capping of injured tooth pulp.

PMID- 18833131
TI  - [Experimental study of the effectiveness of indirect electrochemical blood
      oxidation and antioxidant therapy in the treatment of infectious soft tissue
      wounds].
AB  - In experiments on rats in the process of soft tissues festering wounds treatment
      there was substantiated the inclusion of 0.03% sodium hypochlorite and
      antioxidant <<Recsod>> into basic therapy schedule. These preparations inclusion
      let reduce antioxidant stress and endogenous intoxication levels and eliminate
      disbalance in antioxidant systems of red blood cells and of organism as a whole
      in the acute phase of inflammation and speed up wound heeling processes.

PMID- 18833132
TI  - [Gel Metrogil Denta photopheresis use in comprehensive treatment of patients with
      chronic generalized parodontitis].
AB  - 115 patients with chronic generalized parodontitis of middle or severe degree
      were examined and for them special treatment was developed with laser therapy and
      photophoresis use. The application of mentioned above physical and
      pharmacological methods in comprehensive treatment let to shorten the course of
      treatment and prolong the remission time.

PMID- 18833133
TI  - [Immunological status of patients with caries and its complications in
      combination with parodontitis].
AB  - Results of complex clinical and immunological study of patients with caries and
      pulpitis in combination with periodontitis were presented. It was revealed that
      high intensity of caries and parodontitis combines with significant disturbances
      in cellular and humoral parts of immune system.

PMID- 18833134
TI  - [Model for early childhood caries risks].
AB  - Risk factors of early childhood caries were studied on 406 children of 12-47
      months age. The results showed that pathological pregnancy, sleeping with bottle
      of blend or sweet liquid, use of candy and caramel on sticks and sour-sweet fruit
      juices were significant factors leading to early childhood caries. During
      simultaneous action of all these risk factors domination belonged to use of sour
      sweet fruit juices. The probability of caries occurrence at simultaneous action
      of all these risk factors was equal to 62%.

PMID- 18833135
TI  - [State of local immunity in patients with chronic generalized parodontitis].
AB  - The aim of this work was the determination of the state of local immunity in
      periodontal complex in patients with chronic generalized periodontitis (CGP). 96
      individuals were examined (mean age 43.6+/-1.2 years). All the patients were
      divided into 2 groups: basic group with CGP patients (76 persons) and comparative
      group - individuals with intact periodontium (20 persons). To evaluate local
      immunity in dentogingival fluids the determination of concentrations of IgG, IgM,
      and IgA immunoglobulins has been used, as well as TNF-alpha, IL-1, IL-6, IL-8,
      INF-gamma, IL-1ra, IL-10, and IL-4 cytokines, and also factors controlling the
      state of bone tissue, namely, osteoprotegerine (OPG), and RANK-ligand. In
      gingival fluid of CGP patients the increase in both pro-, and anti-inflammatory
      mediators with indication to Th2-deviation (decrease of INF-gamma level and
      elevation of IL-4 level) was observed. CGP patients exhibited in their
      periodontal complex marked increase of IgG, IgM, and IgA concentrations that
      apparently evidenced to the consequence of local polyclonal activation of B
      lymphocytes. Gingival fluid of CGP patients showed the elevation of RANKL, TNF
      alpha, and IL-1 levels, and the decrease in OPG concentration that could be the
      reason for osteoclast activation and subsequent destruction of bone tissue. In
      case of CGP in the zone of periodontium developed <<atypical>> inflammation that
      is characterized by elevated level of IL-8 and predominance of neutrophil number
      over the quantity of other types of leukocytes.

PMID- 18833136
TI  - [Age peculiarities of combined maxillofacial injuries treatment].
AB  - Experience of help to 399 patients with combined craniofacial traumas of
      different age groups was shown. Some algorithm of help to such patients was
      suggested, interaction of craniofacial trauma components were demonstrated. Some
      scheme of pathogenetic based treatment of patients with combined craniofacial
      injuries was grounded upon it.

PMID- 18833137
TI  - [Computer modelling and topographo-anatomic substantiation of TMJ ankylosis
      surgical treatment].
AB  - Results of topographo-anatomic research of lateral and deep area of face with the
      use of three-dimensional computer modelling was presented. Application of the
      received data at operations of patients with ankilosis of the temporomandibular
      joint gave good results. It allows to draw a conclusion of possibility of this
      technique in a wide clinical practice.

PMID- 18833138
TI  - [Help to patients with injured facial soft tissues and ways of its improvement].
AB  - The structure of premery and specialized medical care to patients with injured
      facial soft tissues based upon statistical information of urgent help dental
      rooms of Samara State Medical University clinics (176 patients) and our own
      clinical data (58 patients) for 2006 and 2007 years was shown. The results of
      clinical and morphological study of operation-biopsy material at different
      periods after trauma were offered. It appeared necessary that the reconstructive
      operations were made in the shortest terms after receiving injuries of facial
      soft tissues and at that by the specialist in maxillofacial surgery. If such
      interventions were performed nether in the full volume, nor with taking into
      account peculiarities of wound healing process, nor by the specialist in
      maxillofacial surgery, functional and aesthetic results were diminished and the
      length of hospital and out-patient periods were prolonged.

PMID- 18833139
TI  - [Diagnostics and comprehensive treatment of patients with odontogenic
      lymphadenitis complicated by phlegmons].
AB  - The duthor detected special changes in oral liquid of macro and trace substances
      concentrations and their ratio in dynamics of convalescence for 24 patients with
      odontogenic lymphadenitis complicated by phlegmon. It was established that
      termination of inflammatory process on earlier terms at addition in complex
      treatment of this pathology of polyvitaminic complex considerably lowering
      strontium concentration in oral liquid (Patent RU 2210378 from 20.08.2003).

PMID- 18833140
TI  - [Use of biologically active preparations in prevention of complication in
      patients with open traumatic mandible fractures].
AB  - Original scheme of clinico-diagnostic treatment of patients with open mandible
      fractures described, based on sufficient clinical material - 100 traumatic
      patients passing the course of stationary and clinic observation. Contemporary
      methods of the objective evaluation of the structural-functional restoration of
      the damaged bone tissues were used for diagnostic purposes. The positive results
      of the study and treatment were obtained. Practical conclusions were made.

PMID- 18833141
TI  - [Results of scientific studies in the field of stomatology in 2006-2007 according
      to the data of Scientific Stomatologic Board].

PMID- 18833142
TI  - [Results of surgical treatment of residual and recurrent anal tumors].
AB  - Radio- or chemotherapy is a modern standard of anal cancer treatment. Recurrence
      or partial remission rate after radiochemotherapy achieves 20-40%. The study is
      aimed to evaluate the role of abdominoperineal resection in the treatment of
      residual and recurrent anal cancer. 120 patients (aged from 30 to 81 (59+/-11)
      years, men:women ratio--1:9) were prospectively studied in the period of 1995 to
      2007. The TNM distribution was as follows: T1-2N0M0--66(55.0%), T3-4N0M0-
      18(15.0%), T1-2N1-3M0--15(12.5%) and T3-4N1-3M0--21(17.5%) patients. The
      radiotherapy delivered in a dose range of 55-65 Gy was used alone or in
      combination with chemotherapy with 5-fluoruracil, mitomycin C or Xeloda. The
      complete tumor regression after radiotherapy/radiochemotherapy was achieved in
      74(61.1%) of 120 patients with cancer-specific survival rate of 81.7%. Partial
      tumor regression was registered in 46 of 120 patients. The abdominoperineal
      resection was performed in 39(84.8%) of patients with the residual tumor. Thus,
      surgical treatment allowed secondary local tumor control in 76.9% of patients
      with the 5-year survival rates of 69.0%. The median survival time for the non
      operated patients, including those, received an extra course of radiotherapy, was
      19 months. The locoregional tumor relapse was diagnosed in 10(13.74%) of 74
      patients with the complete tumor regression. The use of abdominoperineal
      resection allowed the secondary local tumor control and 5 year survival. Thus,
      abdominoperineal resection remains the method of choice in the treatment of
      residual and recurrent anal tumors.

PMID- 18833143
TI  - [Surgical treatment of patients with colorectal cancer and severe concurrent
      cardio-vascular diseases].
AB  - The study population comprised 14 patients, operated on account of colon cancer
      (n=2), sigmoid cancer (n=1), rectal cancer (n=6), synchronous rectal and
      prostatic cancer (n=1) and lung (n=1) and liver (n=2) colon cancer metastases.
      The diagnosed concurrent cardiovascular pathology was: coronary heart disease
      (n=8), valve disease (n=2), aortic aneurism (n=2), coronary heart disease
      combined with aortic aneurism (n=2). Simultaneous operations were performed in 3
      patients, 11 patients were operated on consecutively. No deaths were registered
      after simultaneous operations. In the group of consecutive operations 2 patients
      had died of myocardial infarction and cardiac decompensation. 3 (21,4%) patients
      died of tumor relapse during the follow-up period. The rest 9 patients are under
      observation for 3 months to 10 years, 2 patients achieved a 5-year cancer-free
      survival time.

PMID- 18833144
TI  - [Emergency oncourological surgery in senile patients].
AB  - Many questions of treatment tactics in senile patients remain not quite clear. It
      is necessary to work out an algorithm of surgical treatment depending on severity
      of somatic status of the patient and life prognosis. It is difficult to make a
      decision concerning the necessity and perspectivity of palliative surgical
      treatment of oncological patients at late stages. Taking into account the
      complicacy in prediction of dynamics of malignant growth, active surgical tactics
      with thorough supervision of senile patients with grave somatic status is
      preferable.

PMID- 18833145
TI  - [Reflux esophagitis in patients with short esophagus].
AB  - Pathogenesis, pathophysiology and mechanisms of esophagus contraction by reflux
      esophagitis and hiatal hernia are analyzed. Modern treatment modalities of the
      condition are critically reviewed. Stated, that fundoplication in RSSC
      modification combined with selective proximal vagotomy are indicated for the
      treatment of esophageal contraction stage I. Valvular gastroptyxis is indicated
      when esophageal contraction stage II is diagnosed. Results of valvular
      gastroptyxis in 10 patients are analyzed. The treatment tactics should be
      determined by the degree of esophageal contraction, severity of inflammatory and
      sclerotic changes of the organ and the functional reserve of the esophageal
      motility.

PMID- 18833146
TI  - [The use of cryosupernatant plasma in complex treatment of pancreonecrosis].
AB  - Comparative study of results of complex treatment of pancreonecrosis in 60
      patients using cryosupernatant plasma (CSNP) and fresh frozen plasma was carried
      out. Better positive dynamics in some laboratory indices, less lethality and
      better outcomes were marked with use of CSNP. It can be used instead of fresh
      frozen plasma in complex treatment of pancreonecrosis and concomitant DIC
      syndrome.

PMID- 18833147
TI  - [The function of gastric stump and duodenum after proximal gastric resection in
      patients with esophageal and gastric varicose veins dilatation].
AB  - The authors had developed the technique of proximal gastric resection with
      cardiac orifice plasty. 21 patients with esophageal and varicose veins dilatation
      were operated on using the technique. Follow-up period came from 2 to 23 years.
      Results of the operation allow proximal gastric resection with cardiac orifice
      plasty to be considered the effective way of prevention and treatment of gastric
      bleedings of portal hypertension aetiology.

PMID- 18833148
TI  - [New technologies for the treatment of complicated duodenal ulcers].
AB  - Billroth I gastric resection with end-to-end gastroduodenal anasthamosis was
      carried out to 73 patients with complicated duodenal ulcers using new
      technologies: duodenal mobilization only to the level of ulcer defect, the use of
      one-row (uninterrupted or nodal) everted suture with adaptation zone of submucous
      base of gastric stump and muscle coat of duodenal stump. Good early and long-term
      results were achieved.

PMID- 18833149
TI  - [Laparoscopic treatment of postoperative peritoneal adhesions].
AB  - 75 patients with postoperative peritoneal adhesions, complicated by a severe pain
      syndrome, were operated on during 2003-2006 yy. The preoperative use of the
      enzyme medication <<Collagenase KK>> in 28 patients allowed therefore the
      conduction of adequate laparoscopic adhesiolysis. There were no complications and
      recurrences registered at follow-up. The postoperative hospital stay averaged 3.7
      days.

PMID- 18833150
TI  - [Endoscopic total hip replacement in conditions of acetabulum bone structures
      deficiency].
AB  - 76 patients with acetabulum defects of posttraumatic, oncologic, displastic or
      systemic character, as wall as due to complications after previous hip
      replacement, were operated on. The author's non-tensioned acetabular component
      installation technique worked out for the endoscopic total hip replacement was
      used. Long-term follow-up results were considered to be successful in 88.6% of
      cases. Maximal follow-up period is 10 years.

PMID- 18833151
TI  - [Tactics of surgical treatment of critical lower limbs ischemia and concomitant
      coronary heart disease class III-IV].
AB  - The possibility and use of prolonged epidural anesthesia in terms of preoperative
      care was studied in 78 patients. Patients with various stages of coronary
      arteries affection, central haemodynamics state and risk of reconstructive
      surgical treatment on lower limb arteries were marked out. Patient selection
      criteria for aortocoronary shunting or reconstructive operation on great lower
      limb vessels were worked out. It is proved, that prolonged epidural anesthesia
      allows not only to attain good analgesia but to minimize cardiac complications at
      reconstructive operations on abdominal aorta and its branches.

PMID- 18833152
TI  - [The comparison of laparoscopic and open lymphodissection for gastric cancer].
AB  - Lymphodissection for gastric cancer was performed in 174 patients. Among 116
      patients, operated traditionally, 58% had cancer stages I and II. 58 patients
      operated laparoscopically revealed cancer stages I and II in 55.1%. The mean
      number of removed lymph nodes was 28.9+/-1.2 and was higher after laparoscopic
      operation (p=0.652). The duration of the laparoscopic lymphodissection operation
      was slightly shorter. Blood loss was significantly less during the laparoscopic
      procedure. The mean survival time for patients operated laparoscopically and
      traditionally was 30 and 26.6 months respectively.

PMID- 18833153
TI  - [The infusion therapy of the acute bleeding].
AB  - Intravenous colloid and crystalloid solutions are the mainstay of the acute
      bleeding therapy. Infusion therapy normalizes the blood circulation volume and
      improves its flow characteristics. The conducted study revealed that the method
      normovolemic hemodilution lead to an early unknown type of oxygen insufficiency
      called the dilutional anemic hypoxia. Authors set up and proved the hypothesis,
      that decompensated dilutional anemic hypoxia lead to cardiac insufficiency,
      leading finally to the so called dilutional circulatory hypoxia.

PMID- 18833154
TI  - [The role of radiological methods in complex diagnostics of pancreonecrosis].
AB  - The results of treatment of 77 patients with necrotic forms of acute pancreatitis
      are critically revised. The diagnostic algorithm of pancreonecrosis, consisting
      of ultrasound, computed scanning, magnetic resonance cholangiopancreatography and
      endoscopic retrograde cholangiopancreatography proved to be useful and effective.
      The Balthazar computed tomography severity index allows to prognose the course of
      the disease more accurately.

PMID- 18833155
TI  - [The efficacy of alteplase in pulmonary embolism treatment].
AB  - The results of pulmonary embolism treatment with streptase in 76 patients are
      discussed. All patients had submassive or massive pulmonary embolism. 66 (86%) of
      patients recovered. Thrombolysis with the use of heparin was performed in 9
      patients, death occurred in 5 of them. Of 20 patients treated with "Actilize",
      death was reported in three cases. Authors consider alteplase to be highly
      effective in the treatment of massive pulmonary embolism. In case of late
      diagnostics of pulmonary embolism, especially recurrent, thrombolytic therapy
      remains to be effective up to 2 weeks after primary embolization.

PMID- 18833156
TI  - [The follow-up results of patients with necrotic suppurative forms of diabetic
      foot syndrome].
AB  - Follow-up results of 162 patients with necrotic suppurative forms of the diabetic
      foot syndrome (DFS) are studied in a period of 6 months to 7 years. 51.35% of
      patients with neuropathic form of DFS (NPDFS) relapsed, whereas among patients
      with neuroischemic form (NIDFS) relapse was reported in 61.36% of cases. High
      amputations were performed in 31.58% of patients with NPDFS and in 34.09% in
      patients with NIDFS. Lethality after five years of follow-up was 25.81% after
      shank-level amputation and 50% after hip-level amputation in patients with NPDFS,
      and in the group of NIFDS these numbers amount 57.84% and 72.12%, respectively.
      Authors conclude that compensation of diabetes and its late complications is
      crucial for patients with DFS. Surgical treatment should be maximal sparing, with
      possible foot preservation. Vascular reconstructive surgery should be preferred
      in NIDFS for critical limb ischemia reduction. The level of high limb amputations
      in patients of both groups should be limited by shank when possible.

PMID- 18833157
TI  - [Immunotherapy in complex treatment of surgical sepsis].
AB  - The results of treatment of 73 patients with confirmed diagnosis of sepsis are
      analyzed. The most frequent immune disorders in septic patients are: decrease in
      lymphocyte count, both T (60%) and B (45.7%) populations, decrease of T-helpers
      and T-suppressors (52.6%) count, increase of C3-complement activator titre (50%)
      and phagocytic coefficient (52.4%). The more expressed immune depression observed
      in patients with gram-negative sepsis in comparison with the gram-positive.
      Standard immunoglobulins were used in the treatment of 38 patients: "Endobulin"
      (ImmunoAG, Austria)--in 9 cases; "Intraglobin" (Biotest, Germany)--in 14 and
      "Pentaglobin" (Biotest, Germany)--in 15 cases. Analyze of the control
      immunogramms showed the reliable improvement of immune indices and normalization
      of T-cell counts. Lethality among septic patients treated with immunoglobulins
      was 14.5%.

PMID- 18833158
TI  - [Clinical aspects of diagnostics and surgical treatment of acute primary purulent
      destructive pyelonephritis].
AB  - 79 patients with the acute primary non-obstructive pyelonephritis were treated
      during 2003-2006. 24 (30.3%) patients were operated on with the diagnosis of
      acute primary purulent destructive pyelonephritis. Organopreserving operations
      were performed in 23 (95.8%) of patients. The early diagnostics of purulent
      destructive complications of pyelonephritis, using the developed diagnostic
      algorithm, and modified operative technique allowed to increase the rate of
      organopreserving operations, avoid reinterventions and decrease the risk of
      intraoperative complications.

PMID- 18833159
TI  - [The combined treatment of colorectal cancer with liver metastases].
AB  - The direct and follow-up results of surgical and combined treatment of colorectal
      cancer with liver metastases are presented. Complication rate after liver
      resections was 28.4% and lethality was 3.5%. Follow-up results evidence the
      decrease of survival in patients with adjuvant chemotherapy after surgery. The
      safety of oxalyplatin in patients after liver resections, including its
      intraarterial infusion through the hepatic artery is shown. Oxalyplatin-based
      chemotherapy regimen tended to be more effective in comparison with 5
      fluorouracil scheme, especially in patients with synchronous or multiple liver
      metastases. Considering that the difference is not statistically significant,
      further studies of oxalyplatin influence on survival of patients with colorectal
      liver metastases are necessary.

PMID- 18833160
TI  - [The radical surgical treatment of gastric cancer, complicated with gastric
      bleeding].
AB  - Data of the frequency of profuse gastric bleeding occurrence as the complication
      of gastric cancer are presented. Considering that endoscopic hemostatic
      procedures are ineffective in cancer bleedings, urgent radical surgery is
      indicated. Results of treatment of 10 patients with acute gastric tumor bleeding
      are analyzed. Authors emphasize that local invasion should not be the
      contraindication for the radical tumor resection.

PMID- 18833161
TI  - [The reflux-esophagitis in patients with duodenal ulcer, complicated by
      pyloroduodenal stenosis].
AB  - The function of esophago-gastric junction is studied in 147 patients with ulcer
      pyloroduodenal stenosis before and after the selective proximal vagotomy (SPV)
      procedure. The frequency of reflux-esophagitis was 71.9%. It is determined that
      reflux develops due to gastric evacuatory disorders, reduction of lower
      esophageal sphincter tone and contraction of abdominal part of esophagus. Reflux
      esophagitis develops as the consequence of aggressive gastric juices action on
      the esophageal mucosa. Authors reconstruct the esophageal sphincter mechanism by
      performing the modified fundoplication and fundoesophagocruropexy.

PMID- 18833162
TI  - [The acute small-bowel obstruction caused by periappendicular abscess].
AB  - The diagnostic modes and results of treatment 7 patients with periappendicular
      abscess, complicated by the acute short-bowel obstruction are discussed. Age
      varied from 19 to 76 years. 4 of them were hospitalized with ileus symptoms, the
      rest 5 developed the obstruction during the hospital stay. 2 patients had an
      urgent operation, 4 patients were operated after 2-4 days and 1 after 9 days
      after admission. The correlation between the obstruction symptoms and
      appendicular inflammation was supposed in 3 patients. The cause of small-bowel
      obstruction was twist of the intestine loop, matted to the appendicular abscess.
      The surgery consisted of abscess sanation, appendectomy, small-bowel
      decompression and extrication. One patients died postoperatively of pulmonary
      embolism.

PMID- 18833163
TI  - [The new approach to ventral hernia repair: anatomic and functional basis].
AB  - A new pathogenetically and functionally grounded way of large and giant ventral
      hernia repair is suggested. The anterior wall of rectus sheath is formed with own
      aponeurosis and the posterior wall is formed by the endoprothesis. It reduces the
      risk of the complications, typical for the subcutaneous mesh position and
      provides for elasticity of muscle-aponeurotic abdominal wall structures.
      Satisfactory early and follow-up results are achieved in all 34 patients treated
      using the method. No hernia recurrences were registered.

PMID- 18833164
TI  - [The membrane allotransplantate use in surgery for hygroma].
AB  - Reparative processes in calcaneal tendon after the use of new repair technique
      were studied in two animal series. In both groups the calcaneal tendon was
      incised to the half of its width. In control group no further manipulations were
      performed and in the experimental group the defect was covered with
      allotransplantate of dura mater (membrane stop). The control group demonstrated
      less active tendon reaction, whereas the experimental group demonstrated
      stimulation of reparation with the rapid change of inflammatory stages. The
      membrane stop serves as a modeling frame for new fibers of the regenerate. The
      obtained results permit recommending the membrane stop in treatment of hand
      hygromas for the cover of weak tendon areas.

PMID- 18833165
TI  - [Ultrasonography in differential diagnosis of focal liver neoplasms].
AB  - Results of diagnosis and treatment of 2576 patients with focal lesions of the
      liver are analyzed. Differential ultrasound characteristics for all studied types
      of liver focal lesions are worked out. The effectiveness of the ultrasound
      investigation amounted for echinococcosis 91-95%, non-hydatid cysts--95.5%,
      hepatic tumors--99%, hepatic abscesses--87% and for the hemangioma of the liver-
      76.3%.

PMID- 18833166
TI  - [Schizoaffective psychosis: nosological evaluation and differential diagnosis].
AB  - Basing on the peculiarities of psychopathological presentations and dynamics of
      disease in 253 patients with an ICD-10 diagnosis of schizoaffective disorder
      (F25), the authors argue for the diagnostic validity of this disease.
      Schizoaffective psychosis (SAP) is considered in the context of endoform
      schizophrenic reaction in people with schizotypal personality with signs of
      reactive lability. In the dynamics of a schizoaffective episode, this reaction is
      formed in the period, but not in the structure, of endogenous phasic affective
      disorders and emerges itself as psychotic symptoms characteristic of
      schizophrenia which are independent from circulatory affective symptoms
      pathogenetically and pathokinetically. The clinical peculiarity and specifics of
      clinical-psychopathological presentations of SAP as a diagnostically valid entity
      are discussed. Diagnostic criteria of its differentiation from affective
      disorders and schizoaffective variants of episodic and recurrent schizophrenia
      are presented.

PMID- 18833167
TI  - [Endogenous psychoses with a first episode at the juvenile age: course and
      outcome (follow-up study)].
AB  - A clinical follow-up study (mean duration of the follow-up 16,8+/-6,4 years) of
      278 patients with juvenile endogenous psychosis, episodic type (EPET, ICD-10
      items F20.03, F20.23, F25), with the first episode in 1984-1995, demonstrated
      that the first five years was the period of most intensive manifestation of
      episodes (this period covered about a half of all recurrent episodes). At the
      time of follow-up, a favorable outcome was observed in 18,7% patients, a
      "relatively favorable" - in 33,8%, a "relatively poor" in 17,2%. An analysis of
      correlations of the course and outcome with the variant of the manifesting
      episode and some clinical and pathogenetic parameters allowed to single out a
      number of statistically significant criteria of clinical and social prognosis.
      The nosologic assessment at the time of follow-up showed that 76,2% of patients
      had schizophrenia (episodic-progressive - 61,1%, recurrent - 15,1%) and 23,8% -
      schizoaffective psychosis. A comparison of the present results with the results
      of the earlier study, allows to make a conclusion on the current pathomorphosis
      of EPET with the increase of favorable tendencies in the disease course and
      outcome, reduction of the progression rate and substantial decrease of cases of
      the transition to chronic stage.

PMID- 18833168
TI  - [Correction of motor and affective symptoms of parkinsonism by selective
      serotonine reuptake inhibition antidepressant].
AB  - A study included 68 patients with parkinsonism: 43 of them were treated with
      proflusak (fluoxetin), which efficacy was assessed in the frames of randomized
      placebo-controlled study. The levels of motor disability, anxiety, depression and
      serum serotonin (S) concentration were measured. The prevalence of rigidity and
      hypokinesia caused the increase of the depression level, along with decreasing of
      S concentration. Severity of tremor was positively correlated with the level of
      anxiety and blood S. Significant differences between patients receiving proflusak
      and placebo were found. No changes in the levels of motor-affective symptoms were
      observed in the placebo group. In patients treated with proflusak, the subjective
      improvement of health was accompanied by the significant decrease of depression
      severity and reduction of movement deficit, in particular rigidity and
      hypokinesia. The blood concentration of S decreased significantly in comparison
      to the placebo group. Taking into account the mechanism of action of the drug
      studied (its belonging to SSRIs), these changes may reflect the alterations of
      serotonergic metabolism in the brain synapses.

PMID- 18833169
TI  - [The blood glutathione system in cerebral vascular diseases and its treatment
      with alpha-lipoic acid].
AB  - The changes of glutathione metabolism are rare in dyscirculatory encephalopathy
      and ischemic stroke (IS) of mild severity. The frequent and considerable changes
      have been revealed in IS of moderate and high severity as well as in hemorrhagic
      stroke. An increase of activities of glutathione peroxidase and glutathione
      transferase is the most typical. The increase of enzyme activity was not observed
      at the beginning of treatment after 3 days and in patients with severe degree of
      disease who died later. A standard therapy decreased the quantity and/or
      expression of changes of the glutathione metabolism in patients with IS of
      moderate and high severity while the addition of alpha-lipoic acid (alpha-LA) led
      to the complete normalization in IS of moderate severity and normalization of
      most parameters in IS of high severity. The increase of functional activity of
      the glutathione system at the early stage of treatment of IS and the favorable
      changes during the treatment, in particular after the addition of alpha-LA, were
      correlated with the improvement of neurological status assessed with the NIHSS.
      It has been confirmed that the glutathione system plays an important role in the
      tolerance to brain ischemia.

PMID- 18833170
TI  - [Safety and efficacy of movalis injected into trigger points in lumbago
      ischialgia syndrome].
AB  - Efficacy and safety of movalis (meloxicam) injected into trigger points of 94
      patients with vertebrogenic lumbago-ischialgia syndrome have been assessed.
      Patients have been stratified into 3 randomized groups: the first group received
      3 injections of movalis into trigger points with the following administration of
      tablets (15 mg per day); 2nd group received - 3 intramuscular injection movalis
      with the following administration of tablets (15 mg per day); 3nd - was control.
      Treatment efficacy has been assessed with the Visual-Analogous scale, a five
      point scale for assessment of vertebroneurological symptoms, the Oswestry
      Disability Index, the McGill Pain Questionnaire, stimulating ENMG. Patients
      treated with movalis injections into trigger points and intramuscular had no
      local side-effects. The analgesic effect was more pronounced after three
      injections into trigger points compared to the intramuscular injection. The
      efficacy of treatment was the highest in the first group (75,6%) comparing to the
      2nd (64,3%) and the 3rd (33,3%) ones.

PMID- 18833171
TI  - [The use of axamon in the complex rehabilitation of patients with movement
      disorders in the pathology of lumbar spine].
AB  - The authors review the use of axamon in the complex rehabilitation of
      neurological patients with movement disorders in the pathology of lumbar spine.
      Axamon (ipidacrine) stimulates neuromuscular transmission and excitement
      conduction via nerves and smooth muscles due to the blockade of potassium
      channels of the excited membrane and cholinesterase inhibition. Authors studied
      the efficacy of complex therapy of dorsopathy of lumbar spine in 90 patients
      using axamon, movalis, pantogamum in different combination and manual methodics.
      Patient's status has been measured clinically and with several scales. The
      results obtained allow to conclude that the combination of axamon and pantogamum
      exerts the best theraupetic effect without any side symptoms.

PMID- 18833172
TI  - [Efficacy and tolerability of the combined therapy with mesipol and baclosan in
      chronic recurrent vertebrogenic pain syndrome].
AB  - An article highlights the pathogenetic aspects of treatment of reflex pain
      syndromes in the degenerative-dystrophic spinal lesions. Attention is focused on
      a rational combination of medications that may shorten the duration of analgesic
      and anti-inflammatory therapy to prevent the development of side-effects caused
      by non-steroid anti-inflammatory medications. The results of own research of
      analgesic efficacy and tolerability of treatment in 50 patients with chronic
      skeletal-muscle pain syndromes in the state of exacerbation assigned to the
      combination of a non-steroid anti-inflammatory medication mesipol (meloxicam)
      with a central myorelaxant baclosan (baclofen) are discussed. It was found the
      positive effect of therapy not only on pain syndrome but on comorbid symptoms as
      well.

PMID- 18833173
TI  - [Weight gain in patients with schizophrenia and schizoaffective disorder induced
      by the long-term treatment with atypical antipsychotics].
AB  - To specify the effect of different atypical antipsychotics on weight gain, 346
      patients with schizophrenia and schizoaffective disorder have been examined. The
      influence of risperidone (88 patients), olanzapine (84 patients), clozapine (61
      patients), quetiapine (68 patients) and amisulpiride (45 patients) used as a
      monotherapy has been studied during 1,5 years. Frequency of weight gain for every
      drug and peculiarities of the dynamics of pharmacogenic weight gain and body mass
      index in some stages (after 3, 6, 12 and 18 months) have been revealed. The data
      obtained allow to conclude that the long-term therapy with olanzapine, clozapine
      and risperidone exert a more marked influence on the body mass as compared to
      quetiapine and amisulpiride regardless of the patient's sex.

PMID- 18833174
TI  - [Effectiveness of transcranial magnetic therapy in the complex treatment of
      alcohol abstinent syndrome].
AB  - Fifty-four abstinent alcohol-dependent patients have been studied. Twenty-nine
      patients (a main group) received, along with basic therapy, a physiotherapeutic
      treatment (transcranial dynamic magnetic therapy) and 25 patients (a control
      group) received only basic therapy. The comparison of the efficacy of treatment
      in patients of the main and control groups revealed the benefits of transcranial
      dynamic magnetic therapy in CNS function, performance on memory and attention
      tests, state of autonomic nervous system and psychoemotional state of patients
      (the reduction of anxiety and depression).

PMID- 18833175
TI  - [An electron microscopic study of typical lymphocytes and atypical cells of
      peripheral blood in patients with schizophrenia].
AB  - An electron microscopic analysis of a lymphocyte population from peripheral blood
      of 120 patients with schizophrenia (60 patients with acute and 60 with chronic
      form) and 31 healthy people has been conducted. The ultrastructure and percentage
      of 6 morphofunctional cell types are described. A statistical analysis of the
      data revealed that patients with chronic schizophrenia had the substantially
      increased content of activated lymphocytes, in particular lymphoblasts, while
      patients with acute schizophrenia had the ameliorated content of activated
      lymphocytes along with the increased number of lymphoblasts. The high content of
      lymphoblasts is believed to be a characteristic feature of patients with
      schizophrenia (this type of cells belongs to so-called atypical lymphocytes
      described earlier). The atypical cells include also destructive lymphocytes,
      phagocyting monocytes and phagocyting neutrophiles. These atypical cells are
      observed more often in patients with acute schizophrenia. It has been suggested
      that the presence of an increased number of lymphoblasts in the blood of
      schizophrenic patients indicates the constant production of antigens and the
      presence of phagocyting cells reflects the processes of antigen neutralization.

PMID- 18833176
TI  - [3-D X-ray contrast rotational angiography in vascular pathology diagnostics].
AB  - The experience of 3-D X-ray contrast rotational angiography use is analysed. The
      case examples of virtual applications use on various anatomic areas are
      described. Informational value of routine and 3-D angiography is comparatively
      evaluated. The preferences of modern technology is showed.

PMID- 18833177
TI  - [Proctectomy with external sphincter elements' preservation in surgery of low
      ampullary rectal cancer].
AB  - Operational technique for the rectum tumors, localized at the level of dentate
      line, developed in the State center of coloproctology, allows preservation of
      external anal sphincter elements and thus, partial preservation of defecation
      control. Technique is described and proved, preliminary treatment results of 42
      patients are analysed. The operation is oncologically effective (local recurrence
      rate 4,8%). Preservation of external sphincter elements has a high functional
      value in complex with "neorectum" and "neosphincter". A majority of operated
      patients can keep the stool, 80% of able-bodied patients continued their
      professional activities.

PMID- 18833178
TI  - [Surgical tactics of obturative large bowel tumor obstruction].
AB  - Results of Hartmann operation performed on tumor left colon part obturation in
      general hospitals. Results of 117 patients' treatment were analysed. The local
      tumor recurrence was registered in 17 (14,5%) cases, mean time between initial
      and reconstructive operations was 7,2 months. Results of 61 patients for whom the
      two-step treatment scheme (decompressive colostomy followed by the radical tumor
      resection and a simultaneous stoma closure) was used, are analyzed. Lethality
      rate was 1,6%. Second operation was performed in 58 patients in the mean time of
      18,3 days after colostomy. 7 (12,1%) patients had early postoperative
      complications. Authors conclude that a two-step treatment protocol has advantages
      of higher radicality and the quality of life improvement.

PMID- 18833179
TI  - [Surgical treatment of haemorrhoids].
AB  - The new improved modification of haemorrhoidectomy was warked out. The mucosa is
      dissected 0,5-0,7 sm above the node basis, it is separated sharply from the
      mucosa, whereupon the vascular pedicle is ligated. After cutting the haemorrhoid
      node off, a continuous submucosal suture is used to submerge the stump in the
      submucosal space. In comparison with the traditional technique, the method
      provides prophylaxis of bleedings and inflammatory complications; reduces the
      postoperative pain and dysuria. Submucosal haemorrhoidectomy facilitates the
      primary wound healing, early recovery of microcirculation, perceptibility and
      neuromuscular rectum coordination. Full recovery was achieved after 18,1+/-4,7
      days after the operation.

PMID- 18833180
TI  - [Surgery of rare malignant lung tumours].
AB  - 4023 operations on account of primary bronchopulmonary cancer were performed in
      the period of 1963--2006 years. Rare malignant tumors (carcinoid, adenocystic
      cancer, sarcoma, large cell carcinoma etc.) were diagnosed in 379 (9,1%) cases.
      275 patients of those had bronchpulmonary carcinoid; adenocystic cancer was
      diagnosed in 26 patients; 67 had various types of non-epithelial malignant tumors
      and 11 had a large cell carcinoma. All patients were operated on, morphological
      verification was obtained in all cases. The surgical tactics in patients with
      rare malignant tumours should be the same as for non-small cell lung--lobectomy
      of pneumonectomy with lyphadenectomy. The long term follow-up results witness the
      advisability of surgical treatment.

PMID- 18833181
TI  - [Hilar glissonean access to vascular-secretory elements in anatomical segmental
      liver resections].
AB  - It still remains unclear which patients with hepatic tumors can favour anatomical
      segmental liver resections instead of major liver resection. Short term results
      of anatomical segmental liver resection are evaluated and analyzed. Ten patients
      underwent the anatomical segmental liver resection performed by posterior
      approach with taping of anterior right hepatic vein. Seven patients had liver
      metastases of colorectal cancer, one had primary hepatic carcinoma and two had
      benign lesions, anatomical segmental liver resection were performed without
      Pringle maneuver. There was no significant difference in blood loss, duration of
      the procedure, postoperative hospital stay and morbidity in comparison with the
      segmental liver resection performed by anterior approach. Multiple, large and
      deep-embedded lesions were removed completely, with tumor-free resection margins.
      Anatomical segmental liver resection performed by hilar glissonean approach is
      recommended in patients with compromised liver function "unfavourable" liver
      anatomy to replace major liver resection provides removal of only affected part
      of the liver accordingly to its true anatomical borders.

PMID- 18833182
TI  - [Combined simultaneous operations in emergency surgery and gynecology].
AB  - Results of 927 simultaneous urgent operations performed on account of associated
      surgical and gynaecological pathology were analyzed. Urgent combined operations
      on account of acute gastrointestinal diseases and concomitant gynaecological
      pathology, independently of a primary cause, are advisable and justified. Non
      eliminated concomitant disease or deferred second operation can lead to
      complications. The V (extreme) stage of operative risk can be the
      contraindication to the simultaneous combined surgery.

PMID- 18833183
TI  - [Surgical tactics in treatment of osteomyelitis of long bones].
AB  - The new osteomyelitis classification was worked out on the strength of treatment
      results of 361 patients. Four types of long bones lesions are marked out:
      medullar, superficial, focal and diffuse. The kind of surgical treatment is
      determined according to the lesion type. Authors worked out a modification of
      osteoplastic trepanation--a "grip-sack" technique, which is used for medullar and
      focal femoral and tibial osteomyelitis. Long term follow-up results are obtained
      in 271 (77,7%) cases. The developed classification eases the standardization of
      follow-up results and permits treatment planning.

PMID- 18833184
TI  - [Lower limb distal atherosclerotic gangrene--is high amputation always
      necessary?].
AB  - The results of treatment of patients with systemic atherosclerosis, complicated
      by foot and ankle soft tissue destruction. The majority of such patients are
      amenable to an incapacitating operation--a high femoral amputation. The results
      of arterial reconstructive measures do not always lead to a desirable effect, on
      the contrary, it can worsen the process and lead to a secondary amputation. The
      results of reconstructive treatment of 133 elderly and senile patients showed,
      that arterial reconstructive measures, amplified with necrectomy and minor
      amputation, allow to keep the limb and thus, the quality of life.

PMID- 18833185
TI  - [The choice of esophagoenteroanastomosis after gastrectomy].
AB  - The two years (2004--2006) experience of gastric cancer surgical treatment is
      analized and summarized. 137 had gastrectomy, 73 patients had a combined
      operation because of the extent of the disease. Overall morbidity rate was 19.7%,
      leathality--4,4%. Though, lethality in the group of radically operated patients
      was 0,9%, whereas for those, who could have only palliative surgery, it totaled
      25%. It is established, that performing a Gilyarovitch esophagoenteroanastomosis
      allows to avoid its failure. Gastrectomy with a phrenic segment esophagus
      resection is not a contraindication for the Gilyarovitch
      esophagoenteroanastomosis. The method of small intestine mesentery extension is
      described. It allows to perform a loop anastomosis at the level of phrenic and
      retropericardial esophageal segments. Indications for Roux
      esophagoenteroanastomosis are worked out.

PMID- 18833186
TI  - [Rare cases of primary hydatid cyst of thyroid gland].
AB  - Our experience in surgical treatment of thyroid pathology summarizes the results
      of 4215 cases of nodular, diffuse, toxic and mixed goiter. In only 4 cases the
      hydatid cysts of thyroid gland were diagnosed. The lack of clinical data,
      laboratory and instrumental tests are the main reasons of impossibility of
      correct preoperative diagnose of such a rare form of the disease. The absence of
      diagnostic criteria of other thyroid pathology should prompt a surgeon to think
      about a possibility of a thyroid hydatid cyst.

PMID- 18833187
TI  - [K-ras mutations detection in paraaortic lymph nodes and its prognostic value
      after the surgical treatment of pancreas cancer].
AB  - Survival after surgery of pancreas carcinoma is still poor. Despite an apparently
      curative resection, tumor rapidly recur. Thus, the arsenal of diagnostic means
      should be enriched by sensitive methods to detect the minimal residual disease.
      The frequency of micrometastases in corresponding paraortic lymph nodes after an
      apparently curative operation was detected using routine histological,
      immunohistological and polymerase chain reaction for mutated K-ras methods. Tumor
      tissue was used for the control. 3 cases out of 69 revealed a positive tumor
      histological reaction, and 5--immunohistological staining. K-ras mutations are
      detected in 42 (61%) patients, 12 (17%) of those revealed a positive tumor
      reaction. Only one patient of a control group showed K-ras mutation. All K-ras
      positive patients revealed a poor survival prognosis and had a tumor relapse
      after resection.

PMID- 18833188
TI  - [Ultrasound diagnostics and preoperative staging of rectal cancer].
AB  - Ultrasound (transrectal and transabdominal) examination was performed in 1991
      patients. Rectal tumors were revealed in 117 (5,9%) patients, liver metastases
      were diagnosed in 31 (26,5%) patients. Transrectal ultrasound allowed to diagnose
      tumor in all examined 50 patients. Stage uT2 was diagnosed in 20 (40%) and uT3
      stage of rectum cancer in 30 (60%) of patients. 10 (20%) patients revealed a
      pararectal lymph nodes tumor invasion. All patients were operated on. The
      sensitivity of the method for rectum cancer staging was 95,6%, specificity--40%,
      accuracy 85,7%. Sensitivity of ultrasound in pararectal lymph nodes invasion
      detection was 95,2%, specificity--95,0% and accuracy--92,3%.

PMID- 18833189
TI  - Chromosome fragility at GAA tracts in yeast depends on repeat orientation and
      requires mismatch repair.
AB  - Expansion of triplex-forming GAA/TTC repeats in the first intron of FXN gene
      results in Friedreich's ataxia. Besides FXN, there are a number of other
      polymorphic GAA/TTC loci in the human genome where the size variations thus far
      have been considered to be a neutral event. Using yeast as a model system, we
      demonstrate that expanded GAA/TTC repeats represent a threat to eukaryotic genome
      integrity by triggering double-strand breaks and gross chromosomal
      rearrangements. The fragility potential strongly depends on the length of the
      tracts and orientation of the repeats relative to the replication origin, which
      correlates with their propensity to adopt triplex structure and to block
      replication progression. We show that fragility is mediated by mismatch repair
      machinery and requires the MutSbeta and endonuclease activity of MutLalpha. We
      suggest that the mechanism of GAA/TTC-induced chromosomal aberrations defined in
      yeast can also operate in human carriers with expanded tracts.

PMID- 18833190
TI  - Zili is required for germ cell differentiation and meiosis in zebrafish.
AB  - Small RNAs exert an effect through diverse RNA interference pathways to
      transcriptionally or post-transcriptionally silence their targets. The Piwi
      interacting RNAs (piRNAs) represent a germline-specific small RNA pathway where
      Piwi proteins themselves are thought to mediate piRNA biosynthesis. Here, we
      provide strong evidence for a piRNA amplification loop in zebrafish, in which
      Ziwi and Zili bind piRNAs of opposite polarity. Furthermore, we describe a
      function for Zili in transposon defense and germ cell differentiation, as well as
      a crucial function in meiosis, significantly extending the function of Piwi
      proteins beyond the control of transposable elements in vertebrates.

PMID- 18833191
TI  - Endocochlear potential depends on Cl- channels: mechanism underlying deafness in
      Bartter syndrome IV.
AB  - Human Bartter syndrome IV is an autosomal recessive disorder characterized by
      congenital deafness and severe renal salt and fluid loss. It is caused by
      mutations in BSND, which encodes barttin, a beta-subunit of ClC-Ka and ClC-Kb
      chloride channels. Inner-ear-specific disruption of Bsnd in mice now reveals that
      the positive potential, but not the high potassium concentration, of the scala
      media depends on the presence of these channels in the epithelium of the stria
      vascularis. The reduced driving force for K(+)-entry through mechanosensitive
      channels into sensory hair cells entails a profound congenital hearing loss and
      subtle vestibular symptoms. Although retaining all cell types and intact tight
      junctions, the thickness of the stria is reduced early on. Cochlear outer hair
      cells degenerate over several months. A collapse of endolymphatic space was seen
      when mice had additionally renal salt and fluid loss due to partial barttin
      deletion in the kidney. Bsnd(-/-) mice thus demonstrate a novel function of Cl(-)
      channels in generating the endocochlear potential and reveal the mechanism
      leading to deafness in human Bartter syndrome IV.

PMID- 18833192
TI  - A novel disulphide switch mechanism in Ero1alpha balances ER oxidation in human
      cells.
AB  - Oxidative maturation of secretory and membrane proteins in the endoplasmic
      reticulum (ER) is powered by Ero1 oxidases. To prevent cellular hyperoxidation,
      Ero1 activity can be regulated by intramolecular disulphide switches. Here, we
      determine the redox-driven shutdown mechanism of Ero1alpha, the housekeeping Ero1
      enzyme in human cells. We show that functional silencing of Ero1alpha in cells
      arises from the formation of a disulphide bond-identified by mass spectrometry-
      between the active-site Cys(94) (connected to Cys(99) in the active enzyme) and
      Cys(131). Competition between substrate thiols and Cys(131) creates a feedback
      loop where activation of Ero1alpha is linked to the availability of its
      substrate, reduced protein disulphide isomerase (PDI). Overexpression of
      Ero1alpha-Cys131Ala or the isoform Ero1beta, which does not have an equivalent
      disulphide switch, leads to augmented ER oxidation. These data reveal a novel
      regulatory feedback system where PDI emerges as a central regulator of ER redox
      homoeostasis.

PMID- 18833193
TI  - An isogenetic myoblast expression screen identifies DUX4-mediated FSHD-associated
      molecular pathologies.
AB  - Facioscapulohumeral muscular dystrophy (FSHD) is caused by an unusual deletion
      with neomorphic activity. This deletion derepresses genes in cis; however which
      candidate gene causes the FSHD phenotype, and through what mechanism, is unknown.
      We describe a novel genetic tool, inducible cassette exchange, enabling rapid
      generation of isogenetically modified cells with conditional and variable
      transgene expression. We compare the effects of expressing variable levels of
      each FSHD candidate gene on myoblasts. This screen identified only one gene with
      overt toxicity: DUX4 (double homeobox, chromosome 4), a protein with two
      homeodomains, each similar in sequence to Pax3 and Pax7. DUX4 expression
      recapitulates key features of the FSHD molecular phenotype, including repression
      of MyoD and its target genes, diminished myogenic differentiation, repression of
      glutathione redox pathway components, and sensitivity to oxidative stress. We
      further demonstrate competition between DUX4 and Pax3/Pax7: when either Pax3 or
      Pax7 is expressed at high levels, DUX4 is no longer toxic. We propose a
      hypothesis for FSHD in which DUX4 expression interferes with Pax7 in satellite
      cells, and inappropriately regulates Pax targets, including myogenic regulatory
      factors, during regeneration.

PMID- 18833194
TI  - Curing of the [URE3] prion by Btn2p, a Batten disease-related protein.
AB  - [URE3] is a prion (infectious protein), a self-propagating amyloid form of Ure2p,
      a regulator of yeast nitrogen catabolism. We find that overproduction of Btn2p,
      or its homologue Ypr158 (Cur1p), cures [URE3]. Btn2p is reported to be associated
      with late endosomes and to affect sorting of several proteins. We find that
      double deletion of BTN2 and CUR1 stabilizes [URE3] against curing by several
      agents, produces a remarkable increase in the proportion of strong [URE3]
      variants arising de novo and an increase in the number of [URE3] prion seeds.
      Thus, normal levels of Btn2p and Cur1p affect prion generation and propagation.
      Btn2p-green fluorescent protein (GFP) fusion proteins appear as a single dot
      located close to the nucleus and the vacuole. During the curing process, those
      cells having both Ure2p-GFP aggregates and Btn2p-RFP dots display striking
      colocalization. Btn2p curing requires cell division, and our results suggest that
      Btn2p is part of a system, reminiscent of the mammalian aggresome, that collects
      aggregates preventing their efficient distribution to progeny cells.

PMID- 18833195
TI  - The 'P-usher', a novel protein transporter involved in fimbrial assembly and TpsA
      secretion.
AB  - We identified a new bacterial transporter, the Pseudomonas aeruginosa CupB3
      protein, which is an outer membrane usher involved in pili assembly. In CupB3,
      the usher domain has fused during evolution with a POTRA (polypeptide-transport
      associated)-like domain found in TpsB transporters of two-partner secretion
      systems. In TpsBs, the POTRA captures the TpsA passenger, which is then
      transported across the outer membrane through the TpsB beta-barrel. We named
      CupB3 a 'P-usher' for POTRA-like domain-containing usher. We showed that CupB3
      assembles CupB1 fimbrial subunits into pili and secretes CupB5, a TpsA-like
      protein. The CupB3 usher domain has the function of a TpsB beta-barrel in CupB5
      translocation. We revealed that the POTRA-like domain is neither essential for
      CupB1 fimbriae assembly nor for cell surface exposition of CupB5, but is crucial
      to coordinate bona fide transport of CupB1 and CupB5 through the usher domain.
      The P-usher defines a novel transport pathway involving a molecular machine made
      with old spare parts.

PMID- 18833196
TI  - Hsp104, Hsp70 and Hsp40 interplay regulates formation, growth and elimination of
      Sup35 prions.
AB  - Self-templating amyloid forms of Sup35 constitute the yeast prion [PSI(+)]. How
      the protein-remodelling factor, Hsp104, collaborates with other chaperones to
      regulate [PSI(+)] inheritance remains poorly delineated. Here, we report how the
      Ssa and Ssb components of the Hsp70 chaperone system directly affect Sup35
      prionogenesis and cooperate with Hsp104. We identify the ribosome-associated
      Ssb1:Zuo1:Ssz1 complex as a potent antagonist of Sup35 prionogenesis. The Hsp40
      chaperones, Sis1 and Ydj1, preferentially interact with Sup35 oligomers and
      fibres compared with monomers, and facilitate Ssa1 and Ssb1 binding. Various
      Hsp70:Hsp40 pairs block prion nucleation by disassembling molten oligomers and
      binding mature oligomers. By binding fibres, Hsp70:Hsp40 pairs occlude prion
      recognition elements and inhibit seeded assembly. These inhibitory activities are
      partially relieved by the nucleotide exchange factor, Fes1. Low levels of Hsp104
      stimulate prionogenesis and alleviate inhibition by some Hsp70:Hsp40 pairs. At
      high concentrations, Hsp104 eliminates Sup35 prions. This activity is reduced
      when Ssa1, or enhanced when Ssb1, is incorporated into nascent prions. These
      findings illuminate several facets of the chaperone interplay that underpins
      [PSI(+)] inheritance.

PMID- 18833197
TI  - Association of arterial stiffness with the angiotensin-converting enzyme gene
      polymorphism in healthy individuals.
AB  - BACKGROUND: Arterial stiffness is an important determinant of cardiovascular
      morbidity and mortality. The I/D polymorphism of angiotensin-converting enzyme
      (ACE) gene is associated with cardiovascular disease. However, the relationship
      between ACE polymorphism, arterial stiffness, and wave reflections in healthy,
      low-risk population has not been defined yet. METHODS: The study included 282
      apparently healthy, low-risk individuals (mean age 39.7 +/- 8.9 years, 178
      males). Carotid-femoral pulse wave velocity (PWV) was measured as an index of
      aortic stiffness, while wave reflections were assessed by augmentation index
      (AIx) of the central pressure waveform. I/D polymorphism of the ACE gene was
      determined in all subjects for the prevalence of the DD, ID, and II genotype (39,
      44, and 17%, respectively). C-reactive protein (CRP) levels were determined as a
      marker of chronic, subclinical inflammation. RESULTS: After adjustment for
      potential confounding factors, presence of D allele was associated with lower
      values of PWV compared to II genotype (P < 0.05), implying lower aortic stiffness
      for D allele carriers. There was no association between ACE genotype and wave
      reflections or peripheral and central systolic pressures. CONCLUSIONS: In
      apparently healthy individuals, D allele is associated with lower aortic
      stiffness, whereas there is no association of the ACE polymorphism with wave
      reflections. This finding provides new insights into the possible links between
      ACE gene, regulation of large artery stiffness, and has implications for
      cardiovascular risk.

PMID- 18833198
TI  - Night time blood pressure variability is a strong predictor for cardiovascular
      events in patients with type 2 diabetes.
AB  - BACKGROUND: We aimed this study to test the hypothesis that short-term blood
      pressure (BP) variability and abnormal patterns of diurnal BP variation,
      evaluated by ambulatory BP (ABP), predicts risk of incident cardiovascular
      disease (CVD) in patients with type 2 diabetes (T2DM). METHODS: ABP monitoring
      (ABPM) was performed in 300 patients with uncomplicated T2DM without known CVD
      and without BP medications, who were followed for 54 +/- 20 months. The
      relationships of different measures of BP variability, the presence of abnormal
      patterns of diurnal BP variation (nondipper, riser, or morning BP surge) and the
      standard deviations of awake and asleep ABP were determined. Cox proportional
      hazards models were used to estimate hazard ratios (HRs) and their 95% confidence
      intervals (CIs) before and after controlling for various covariates. RESULTS: The
      mean age was 67.8 +/- 9.6 years, 48% were male, 253 (84%) had a diagnosis of
      hypertension, and the mean of the standard deviations of awake systolic
      BP/diastolic BP (SBP/DBP) were 18 +/- 6/11 +/- 4 mm Hg, and those of sleep
      SBP/DBP were 13 +/- 5/9 +/- 3 mm Hg. During follow-up, there were 29
      cardiovascular events. In multivariable analyses, the standard deviations of
      sleep SBP (HR = 1.08; 95% CI, 1.01-1.16, P < 0.05) and sleep DBP (HR = 1.13; 1.04
      1.23, P < 0.01) were independently associated with incident CVD. Neither the
      nondipper and riser patterns nor the morning BP surge were associated with
      incident CVD events independently of clinic and 24-h BP levels. CONCLUSIONS:
      Abnormal diurnal BP variation was not a predictor of CVD in patients with T2DM.
      Night time BP variability was an independent predictor of future incidence of
      CVD, suggesting that this measure could reflect pathophysiology of T2DM.

PMID- 18833199
TI  - The SCX/IMAC enrichment approach for global phosphorylation analysis by mass
      spectrometry.
AB  - The success in profiling the phosphoproteome by mass spectrometry-based
      proteomics has been intimately related to the availability of methods that
      selectively enrich for phosphopeptides. To this end, we describe a protocol that
      combines two sequential enrichment steps. First, strong cation exchange (SCX)
      chromatography separates peptides by solution charge. Phosphate groups contribute
      to solution charge by adding a negative charge at pH 2.7. Therefore, at that pH,
      phosphopeptides are expected to elute earlier than their nonphosphorylated
      homologs. Second, immobilized metal affinity chromatography (IMAC) takes
      advantage of phosphate's affinity for metal ions such as Fe(3+) to uniformly
      enrich for phosphopeptides from the previously collected SCX fractions. We have
      successfully employed the SCX/IMAC enrichment strategy in the exploration of
      phosphoproteomes from several systems including mouse liver and Drosophila
      embryos characterizing over 5,500 and 13,000 phosphorylation events,
      respectively. The SCX/IMAC enrichment protocol requires 2 days, and the entire
      procedure from cells to a phosphorylation data set can be completed in less than
      10 days.

PMID- 18833200
TI  - A convenient, high-throughput method for enzyme-luminescence detection of
      dopamine released from PC12 cells.
AB  - This protocol represents a novel enzyme-luminescence method to detect dopamine
      sensitively and rapidly with high temporal resolution. In principle, dopamine is
      first oxidized with tyramine oxidase to produce H(2)O(2), and then the produced
      H(2)O(2) reacts with luminol to generate chemiluminescence in the presence of
      horseradish peroxidase (POD). We applied this method successfully to perform real
      time monitoring of dopamine release from PC12 cells using a luminescence plate
      reader upon stimulation with several drugs (e.g., acetylcholine, bradykinin). The
      results indicated that the dopamine release from PC12 cells was modulated by
      these drugs in a way similar to that found by using several conventional
      analytical techniques, such as HPLC-electrochemical detector (ECD). Unlike other
      assays, this assay technique is simple, rapid, highly sensitive and thus useful
      for assessment of effects of drugs on the nervous system. The dopamine release
      assay takes only < or =1 h once reagent setup and culture plates' preparation are
      finished.

PMID- 18833201
TI  - Ex vivo imaging of motor axon dynamics in murine triangularis sterni explants.
AB  - We provide a protocol that describes an explant system that allows the dynamics
      of motor axons to be imaged. This method is based on nerve-muscle explants
      prepared from the triangularis sterni muscle of mice, a thin muscle that covers
      the inside of the thorax. These explants, which can be maintained alive for
      several hours, contain long stretches of peripheral motor axons including their
      terminal arborizations and neuromuscular junctions. Explants can be prepared from
      transgenic mouse lines that express fluorescent proteins in neurons or glial
      cells, which enables direct visualization of their cellular and subcellular
      morphology by fluorescence microscopy. Time-lapse imaging then provides a
      convenient and reliable approach to follow the dynamic behavior of motor axons,
      their surrounding glial cells and their intracellular organelles with high
      temporal and spatial resolution. Triangularis sterni explants can be prepared in
      15 min, imaged ex vivo for several hours and processed for immunohistochemistry
      in about 2 h.

PMID- 18833202
TI  - Atomic force microscopy of supported lipid bilayers.
AB  - Supported lipid bilayers (SLBs) are widely used in biophysical research to
      investigate the properties of biological membranes and offer exciting prospects
      in nanobiotechnology. Atomic force microscopy (AFM) has become a well-established
      technique for imaging SLBs at nanometer resolution. A unique feature of AFM is
      its ability to monitor dynamic processes, such as the interaction of bilayers
      with proteins and drugs. Here, we present protocols for preparing
      dioleoylphosphatidylcholine/dipalmitoylphosphatidylcholine (DOPC/DPPC) bilayers
      supported on mica using small unilamellar vesicles and for imaging their
      nanoscale interaction with the antibiotic azithromycin using AFM. The entire
      protocol can be completed in 10 h.

PMID- 18833203
TI  - Catalytic alkynone generation by Sonogashira reaction and its application in
      three-component pyrimidine synthesis.
AB  - The Sonogashira alkynylation of acid chlorides can be efficiently conducted in
      less than an hour by performing the reaction in tetrahydrofuran as a solvent and
      in the presence of one stoichiometrically necessary equivalent of triethylamine
      as a base. This approach also opens new avenues for consecutive one-pot
      multicomponent reactions. As an example, the one-pot three-component pyrimidine
      synthesis illustrates the versatility of this modified Sonogashira protocol as an
      entry to diversity-oriented heterocycle synthesis in a one-pot fashion. The
      protocol can be completed within a few hours.

PMID- 18833204
TI  - Noncatalytic reaction of isonitriles and carboxylic acids en route to amide-type
      linkages.
AB  - This protocol describes the preparation of an N-methyl-asparagine-linked glycosyl
      amino acid, on the basis of a reaction between carboxylic acids and isonitriles.
      Under microwave/thermolysis, carboxylic acids can couple with isonitriles without
      an external catalyst to form N-formyl-amides, which may be further advanced to
      the corresponding amides, N-methyl amide and N-methyloyl amide. The example
      reaction of beta-galactopyranosyl isonitrile (7) with a protected aspartic acid
      under microwave condition in 30 min stereoselectively leads to a beta
      galactopyranosyl-N-formyl-asparagine (9). Further chemical transformations
      readily convert 9 into beta-galactopyranosyl-N-methyl-asparagine (11).

PMID- 18833205
TI  - Agrobacterium-mediated transformation of the filamentous fungus Aspergillus
      awamori.
AB  - Many transformation methods have been developed to introduce DNA into filamentous
      fungi. One of these methods is Agrobacterium-mediated transformation (AMT). Here,
      we describe an efficient protocol for AMT of Aspergillus awamori. This protocol
      has been used to determine the function of Agrobacterium virulence genes during
      AMT, to identify factors influencing transformation frequencies, to generate
      insertional mutants and to generate A. awamori gene knockout transformants. This
      protocol in not only applicable to A. awamori, but can be used as a more general
      guideline for AMT of other filamentous fungi. Conidiospores are incubated with
      induced Agrobacterium, and, after a cocultivation and selection period,
      hygromycin-resistant transformants are obtained with a frequency of 200-250
      transformants per 1 x 10(6) conidiospores. Using this protocol, transformants can
      be obtained within 10-12 d.

PMID- 18833206
TI  - A personal digital assistant application (MobilDent) for dental fieldwork data
      collection, information management and database handling.
AB  - OBJECTIVE: To develop a personal digital assistant (PDA) application for oral
      health assessment fieldwork, including back-office and database systems
      (MobilDent). DESIGN: System design, construction and implementation of PDA, back
      office and database systems. METHODS: System requirements for MobilDent were
      collected, analysed and translated into system functions. User interfaces were
      implemented and system architecture was outlined. MobilDent was based on a
      platform with. NET (Microsoft) components, using an SQL Server 2005 (Microsoft)
      for data storage with Windows Mobile (Microsoft) operating system. The PDA
      devices were Dell Axim. RESULTS: System functions and user interfaces were
      specified for MobilDent. User interfaces for PDA, back-office and database
      systems were based on. NET programming. The PDA user interface was based on
      Windows suitable to a PDA display, whereas the back-office interface was designed
      for a normal-sized computer screen. A synchronisation module (MS Active Sync,
      Microsoft) was used to enable download of field data from PDA to the database.
      CONCLUSIONS: MobilDent is a feasible application for oral health assessment
      fieldwork, and the oral health assessment database may prove a valuable source
      for care planning, educational and research purposes. Further development of the
      MobilDent system will include wireless connectivity with download-on-demand
      technology.

PMID- 18833207
TI  - Anaesthetic efficacy of a labial infiltration method on the nasopalatine nerve.
AB  - BACKGROUND AND AIM: The conventional nasopalatine nerve block is commonly used to
      obtain anaesthesia in the anterior portion of the palate. The painful nature of
      this approach, however, has led investigators to seek alternative methods to
      obtain anaesthesia. Labial infiltration of the maxillary central incisors can be
      considered an effective anaesthetic approach for the anterior palate. Our study
      aimed to assess the anaesthetic effect of a modified labial infiltration method
      on the nasopalatine nerve. MATERIALS AND METHOD: A case-control clinical trial
      was done on 60 patients referring for extraction of maxillary incisors (mean age
      44 years). The patients were divided into two groups of 30 people. For the first
      group, a primary conventional infiltration was given to each patient from a point
      between the maxillary canine and the lateral to obtain preliminary anaesthesia
      for the maxillary anterior labial area. The second or the control group was
      anaesthetised by conventional injection into incisive papilla. Two to three
      minutes afterwards, a labial infiltration approach was done and the amount of
      pain determined by OPS (objective pain score) was assessed. After five to six
      minutes the level of anaesthesia in the anterior palate was assessed in both
      groups by an explorer and recorded as pain-free, mild pain or severe pain. The
      sign test was used to statistically analyse the data (p <0.001). RESULTS: Total,
      moderate and no anaesthesia were observed in 76.7%, 13.3%, and 10% of the
      patients receiving anesthetic injection at the labial side. For the control
      group, these results were 83%, 17% and 0% respectively. CONCLUSION: This method
      of labial infiltration may be an effective alternative to the painful
      conventional palatine nerve block to obtain efficient anaesthesia of the anterior
      palate (p <0.001).

PMID- 18833208
TI  - Full-mouth treatment versus quadrant root surface debridement in the treatment of
      chronic periodontitis: a systematic review.
AB  - BACKGROUND AND AIMS: Non-surgical periodontal therapy has been proven to be an
      effective treatment for patients with chronic periodontitis. Conventional non
      surgical therapy by debridement of the root surfaces is performed on a quadrant
      basis with 1-2 week intervals. This time interval may result in re-colonisation
      by the bacteria of the instrumented pockets and impair healing. Therefore, a new
      approach of full-mouth non-surgical therapy to be completed within two
      consecutive days with (full-mouth disinfection) or without (full-mouth
      debridement) use of oral antiseptics has been suggested. The aim of this review
      was to compare the clinical outcomes of the three modalities of non-surgical
      therapy (full-mouth disinfection [FMD], full-mouth debridement [FRp], quadrant
      scaling and root planing [Q]). METHODS: Standard searches of Medline and Embase
      databases and appropriate hand searching provided the published studies, which
      were then assessed against pre-determined inclusion criteria. Meta-analysis was
      performed wherever possible using Review Manager 4.2 software. RESULTS: Seven
      randomised controlled trials (RCTs) were included in the review and these failed
      to show any statistically significant differences between the FRp and Q
      approaches. Further studies are required to reach conclusion regarding the
      advantages of FMD approach. PRACTICAL IMPLICATIONS: Mechanical debridement is an
      important component of treatment for chronic periodontitis and this review
      suggests that both the traditional quadrant approach and the newer the full-mouth
      debridement could be equally effective.

PMID- 18833209
TI  - Is there scope for providing oral cancer health advice in dental access centres?
AB  - OBJECTIVE: There are more than 3,500 new cases of oral cancer each year in the
      UK. The purpose of this study was to establish the proportion of patients
      attending a dental access centre that are at risk of developing oral cancer
      because of lifestyle habits, and in turn determine whether access centres are a
      suitable location for the provision of advice on smoking cessation and alcohol
      consumption. METHODS: Data were collected prospectively about the smoking and
      drinking habits of patients attending a dental access centre in Nottingham. Three
      hundred and fifty-nine patients attended the dental access centre during the
      survey period. Patients were categorised into one of four groups ranging from low
      risk to high risk, according to their smoking history and alcohol intake.
      RESULTS: More than 50% of patients attending the dental access centre were
      smokers, with almost 40% of the patients in high or very high tobacco and alcohol
      use groups. The majority of attendees were under 45 years of age. CONCLUSIONS:
      Significant numbers of patients attending the dental access centre have lifestyle
      habits that make them vulnerable to oral cancer. Dental access centres could
      usefully provide opportunistic health messages to patients about risk factors in
      the development of oral cancer.

PMID- 18833210
TI  - The FTO gene and obesity in a large Eastern European population sample: the
      HAPIEE study.
AB  - Variants in the FTO (oxoglutarate-dependent nucleic acid demethylase) gene have
      been associated with the BMI determination in Western European and North American
      populations. To widen the geographical coverage of the FTO studies, we have
      analyzed the association between the FTO gene variant rs17817449 (G>C) and
      obesity in a Slavic Eastern European population. A total of 3,079 males and 3,602
      females 45-69 years old were randomly selected from population registers of seven
      Czech cities. We examined three indices of obesity: BMI (kg/m(2)), waist
      circumference, and waist-to-hip ratio (WHR). The FTO rs17817449 variant was
      significantly associated with BMI both in males (GG 28.7 +/- 4.1; GT 28.3 +/-
      3.9; TT 28.0 +/- 3.9; P = 0.003) and females (GG 28.7 +/- 5.2; GT 28.2 +/- 5.1;
      TT 27.2 +/- 4.9; P < 0.001); the associations were not affected by adjustment for
      age, smoking, socioeconomic status, and physical activity. The FTO variant was
      also associated with waist circumference (difference between GG and TT was 1.1 cm
      (P = 0.043) in men and 2.4 cm (P < 0.001) in women) but this relationship
      disappeared after adjustment for BMI. Similarly, BMI explained the weak
      association of FTO with WHR and C-reactive protein. FTO was not associated with
      plasma total and high-density lipoprotein cholesterol, triglycerides, blood
      glucose, and blood pressure. These results confirm that in a Slavic population
      the FTO variant is strongly associated with BMI but not with other risk factors.

PMID- 18833211
TI  - Validation of a parent-proxy, obesity-specific quality-of-life measure: sizing
      them up.
AB  - The aims of the present study were to develop and validate a new obesity
      specific, parent-proxy measure of health-related quality of life (HRQOL), Sizing
      Them Up. Participants included 220 obese youth (M(age) = 11.6 years, 68% female,
      53% African American, M(BMI) = 36.7) and their primary caregivers (88% mothers).
      Primary caregivers completed a demographics questionnaire and two HRQOL measures:
      Sizing Them Up (obesity-specific) and PedsQL (generic). Youth height and weight
      were measured. Psychometric evaluation of Sizing Them Up was completed by
      conducting a factor analysis and determining internal consistency coefficients,
      test-retest reliability, convergent and discriminant validity, predictive
      validity, responsiveness to change, and minimal clinically important difference
      (MCID) scores. Sizing Them Up is a 22-item measure with six scales (i.e.,
      Emotional Functioning, Physical Functioning, Teasing/Marginalization, Positive
      Social Attributes, Mealtime Challenges, and School Functioning) that account for
      66% of the variance. The measure also includes an Adolescent Developmental
      Adaptation module. Sizing Them Up had internal consistency coefficients ranging
      from 0.59 to 0.91 and test-retest reliabilities ranging from 0.57 to 0.80.
      Validity was demonstrated by significant relations between a majority of Sizing
      Them Up scales and BMI z-scores. Sizing Them Up also demonstrated good convergent
      validity with other HRQOL measures and responsiveness to change related to weight
      loss for adolescents who had undergone bariatric surgery. Overall, Sizing Them Up
      is a reliable and valid parent-proxy measure of obesity-specific HRQOL that can
      be used in both clinical and research settings.

PMID- 18833212
TI  - Increased myocardial susceptibility to repetitive ischemia with high-fat diet
      induced obesity.
AB  - Obesity and diabetes are frequently associated with cardiovascular disease. When
      a normal heart is subjected to brief/sublethal repetitive ischemia and
      reperfusion (I/R), adaptive responses are activated to preserve cardiac structure
      and function. These responses include but are not limited to alterations in
      cardiac metabolism, reduced calcium responsiveness, and induction of antioxidant
      enzymes. In a model of ischemic cardiomyopathy inducible by brief repetitive I/R,
      we hypothesized that dysregulation of these adaptive responses in diet-induced
      obese (DIO) mice would contribute to enhanced myocardial injury. DIO C57BL/6J
      mice were subjected to 15 min of daily repetitive I/R while under short-acting
      anesthesia, a protocol that results in the development of fibrotic
      cardiomyopathy. Cardiac lipids and candidate gene expression were analyzed at 3
      days, and histology at 5 days of repetitive I/R. Total free fatty acids (FFAs) in
      the cardiac extracts of DIO mice were significantly elevated, reflecting
      primarily the dietary fatty acid (FA) composition. Compared with lean controls,
      cardiac FA oxidation (FAO) capacity of DIO mice was significantly higher,
      concurrent with increased expression of FA metabolism gene transcripts. Following
      15 min of daily repetitive I/R for 3 or 5 days, DIO mice exhibited increased
      susceptibility to I/R and, in contrast to lean mice, developed microinfarction,
      which was associated with an exaggerated inflammatory response. Repetitive I/R in
      DIO mice was associated with more profound significant downregulation of FA
      metabolism gene transcripts and elevated FFAs and triglycerides. Maladaptive
      metabolic changes of FA metabolism contribute to enhanced myocardial injury in
      diet-induced obesity.

PMID- 18833213
TI  - Postnatal catch-up growth after fetal protein restriction programs proliferation
      of rat preadipocytes.
AB  - We studied the in vitro proliferation and differentiation of rat preadipocytes to
      investigate whether catch-up growth after prenatal protein restriction may
      program adipose precursor cells leading to development of increased adipose
      tissue mass. Pregnant rat dams were fed either an isocaloric low-protein diet (LP
      8%) or control diet (C-20%). During lactation, in order to induce catch-up
      growth, dams from LP group were fed with the C diet and litter size was reduced
      to four pups instead of eight. Preadipocytes were isolated from weanling male
      pups (28 days of age). Differentiation and proliferation were assessed across
      time. At late stages of preadipocyte differentiation, no difference was observed
      in lipid accumulation of C or LP cultures but the mRNA expression of leptin was
      enhanced in LP cells. At early stages of culture, a higher DNA and protein
      content accompanied by a higher rate of proliferation was measured in adipocytes
      from LP cultures. Moreover, the mRNA expression of cyclin D1 was increased in
      these cells whereas the expression of peroxisome proliferators-activated receptor
      gamma (PPARgamma) and steroyl regulatory element binding protein (SREBP-1c) was
      significantly reduced during early stages. The results suggest that prenatal
      exposure to a LP followed by rapid catch-up growth is associated with a higher
      rate for proliferation in preadipocytes.

PMID- 18833214
TI  - TOF-SIMS analysis of lipid accumulation in the skeletal muscle of ob/ob mice.
AB  - Skeletal muscle lipid accumulation is associated with several chronic metabolic
      disorders, including obesity, insulin resistance (IR) and type 2 diabetes. The
      aim of this study is to evaluate whether static imaging time-of-flight-secondary
      ion mass spectrometry (TOF-SIMS) equipped with a Bismuth-cluster ion source can
      be used for studying skeletal muscle lipid accumulation associated with obesity.
      Mouse gastrocnemius muscle tissues in 10-week-old obese ob/ob (n = 8) and lean
      wild-type C57/BL6 (n = 6) mice were analyzed by TOF-SIMS. Our results showed that
      signal intensities of fatty acids (FAs) and diacylglycerols (DAGs) were
      significantly increased in skeletal muscle of the obese ob/ob mice as compared to
      the lean wild-type mice. These differences were revealed through a global
      analytical approach, principal component analysis (PCA) of TOF-SIMS spectra, and
      ion-specific TOF-SIMS images. Region-of-interest (ROI) analysis showed that FA
      signal intensities within the muscle cell were significantly increased in ob/ob
      mice. Moreover, analysis of the ratio between different FA peaks revealed changes
      in monounsaturated FAs (MUFAs) and polyunsaturated FAs (PUFAs), which is in
      agreement with previous reports on obesity. These changes in FA composition were
      also reflected in the ratio of different DAGs or phosphatidylcholines (PCs) that
      contain different FA residues. Imaging TOF-SIMS together with PCA of TOF-SIMS
      spectra is a promising tool for studying skeletal muscle lipid accumulation
      associated with obesity.

PMID- 18833215
TI  - Approaching a renaissance in coma research responsibly.

PMID- 18833216
TI  - McArdle disease: what do neurologists need to know?
AB  - McArdle disease (also known as glycogen storage disease type V) is a pure
      myopathy caused by an inherited deficit of myophosphorylase, the skeletal muscle
      isoform of the enzyme glycogen phosphorylase. The disease exhibits clinical
      heterogeneity, but patients typically experience exercise intolerance, that is,
      reversible, acute crises (early fatigue and contractures, sometimes with
      rhabdomyolysis and myoglobinuria) triggered by static muscle contractions (e.g.
      lifting weights) or dynamic exercise (e.g. climbing stairs or running). In this
      Review, we discuss the main features of McArdle disease, with the aim of
      providing neurologists with up-to-date, useful information to assist their
      patients. The topics covered include diagnostic tools-for example, molecular
      genetic diagnosis, the classic ischemic forearm test and the so-called 'second
      wind' phenomenon-and current therapeutic options-for example, a carbohydrate-rich
      diet and carbohydrate ingestion shortly before strenuous exercise, in combination
      with medically supervised aerobic training of low to moderate intensity.

PMID- 18833217
TI  - Photoemission kinks and phonons in cuprates.

PMID- 18833221
TI  - A question of balance.

PMID- 18833222
TI  - Life after Zerhouni.

PMID- 18833223
TI  - An end to secrecy.

PMID- 18833235
TI  - NIH soon to be leaderless.

PMID- 18833236
TI  - Hwang work granted patent.

PMID- 18833237
TI  - Credit crunch threatens US wind-energy projects.

PMID- 18833238
TI  - Teams merge for dark-energy mission.

PMID- 18833247
TI  - Military research: the Pentagon's culture wars.

PMID- 18833248
TI  - Cell therapy: being patient.

PMID- 18833249
TI  - Further reflections on how we interpret the actions of others.

PMID- 18833250
TI  - Austria: Academy of Sciences states its case.

PMID- 18833251
TI  - Don't release other people's data without their consent.

PMID- 18833252
TI  - Don't forget people and specimens that make the database.

PMID- 18833253
TI  - Religion and science: separated by an unbridgeable chasm.

PMID- 18833254
TI  - Science journals have been slow to make themselves audible.

PMID- 18833255
TI  - Religion and science: a guide for the 'perplexed'.

PMID- 18833256
TI  - HIV immunology needs a new direction.

PMID- 18833257
TI  - UK physics gets a health check.

PMID- 18833260
TI  - Q&A: Creations from the cosmos. Interviewed by Jennifer Rohn.

PMID- 18833263
TI  - Beijing 1987: China's coming-out party.

PMID- 18833264
TI  - Sensory ecology: in sight of speciation.

PMID- 18833265
TI  - Climate change: when did the icehouse cometh?

PMID- 18833266
TI  - Regenerative medicine: short cut to cell replacement.

PMID- 18833267
TI  - AIDS: prehistory of HIV-1.

PMID- 18833268
TI  - Applied physics: virtues of diamond defects.

PMID- 18833269
TI  - Neuroscience: fragile dopamine.

PMID- 18833270
TI  - The changing face of HIV in China.
AB  - HIV has advanced from high-risk groups such as intravenous drug users to some in
      the general population, according to comprehensive new data from the south of
      China. What needs to be done to halt its spread?

PMID- 18833271
TI  - Challenges in the development of an HIV-1 vaccine.
AB  - The development of a safe and effective human immunodeficiency virus (HIV)-1
      vaccine is a critically important global health priority. Despite recent advances
      in our understanding of HIV-1 pathogenesis and immunology, however, major
      scientific obstacles remain. Prototype HIV-1 vaccine candidates aimed at
      eliciting humoral and cellular immune responses have so far failed to protect
      against HIV-1 infection or to reduce viral loads after infection in clinical
      efficacy studies. A renewed and coordinated commitment to basic discovery
      research, preclinical studies and clinical trials will therefore be required to
      overcome the hurdles currently facing the field. Here I review key challenges and
      future prospects in the quest to develop a prophylactic HIV-1 vaccine.

PMID- 18833272
TI  - Speciation through sensory drive in cichlid fish.
AB  - Theoretically, divergent selection on sensory systems can cause speciation
      through sensory drive. However, empirical evidence is rare and incomplete. Here
      we demonstrate sensory drive speciation within island populations of cichlid
      fish. We identify the ecological and molecular basis of divergent evolution in
      the cichlid visual system, demonstrate associated divergence in male colouration
      and female preferences, and show subsequent differentiation at neutral loci,
      indicating reproductive isolation. Evidence is replicated in several pairs of
      sympatric populations and species. Variation in the slope of the environmental
      gradients explains variation in the progress towards speciation: speciation
      occurs on all but the steepest gradients. This is the most complete demonstration
      so far of speciation through sensory drive without geographical isolation. Our
      results also provide a mechanistic explanation for the collapse of cichlid fish
      species diversity during the anthropogenic eutrophication of Lake Victoria.

PMID- 18833273
TI  - An 84-microG magnetic field in a galaxy at redshift z = 0.692.
AB  - The magnetic field pervading our Galaxy is a crucial constituent of the
      interstellar medium: it mediates the dynamics of interstellar clouds, the energy
      density of cosmic rays, and the formation of stars. The field associated with
      ionized interstellar gas has been determined through observations of pulsars in
      our Galaxy. Radio-frequency measurements of pulse dispersion and the rotation of
      the plane of linear polarization, that is, Faraday rotation, yield an average
      value for the magnetic field of B approximately 3 microG (ref. 2). The possible
      detection of Faraday rotation of linearly polarized photons emitted by high
      redshift quasars suggests similar magnetic fields are present in foreground
      galaxies with redshifts z > 1. As Faraday rotation alone, however, determines
      neither the magnitude nor the redshift of the magnetic field, the strength of
      galactic magnetic fields at redshifts z > 0 remains uncertain. Here we report a
      measurement of a magnetic field of B approximately 84 microG in a galaxy at z =
      0.692, using the same Zeeman-splitting technique that revealed an average value
      of B = 6 microG in the neutral interstellar gas of our Galaxy. This is
      unexpected, as the leading theory of magnetic field generation, the mean-field
      dynamo model, predicts large-scale magnetic fields to be weaker in the past
      rather than stronger.

PMID- 18833274
TI  - Clustered star formation as a natural explanation for the Halpha cut-off in disk
      galaxies.
AB  - The rate of star formation in a galaxy is often determined by the observation of
      emission in the Halpha line, which is related to the presence of short-lived
      massive stars. Disk galaxies show a strong cut-off in Halpha radiation at a
      certain galactocentric distance, which has led to the conclusion that star
      formation is suppressed in the outer regions of disk galaxies. This is seemingly
      in contradiction to recent observations in the ultraviolet which imply that disk
      galaxies have star formation beyond the Halpha cut-off, and that the star
      formation-rate surface density is linearly related to the underlying gas surface
      density, which is a shallower relationship than that derived from Halpha
      luminosities. In a galaxy-wide formulation, the clustered nature of star
      formation has recently led to the insight that the total galactic Halpha
      luminosity is nonlinearly related to the galaxy-wide star formation rate. Here we
      show that a local formulation of the concept of clustered star formation
      naturally leads to a steeper radial decrease in the Halpha surface luminosity
      than in the star-formation-rate surface density, in quantitative agreement with
      the observations, and that the observed Halpha cut-off arises naturally.

PMID- 18833275
TI  - Nanoscale magnetic sensing with an individual electronic spin in diamond.
AB  - Detection of weak magnetic fields with nanoscale spatial resolution is an
      outstanding problem in the biological and physical sciences. For example, at a
      distance of 10 nm, the spin of a single electron produces a magnetic field of
      about 1 muT, and the corresponding field from a single proton is a few
      nanoteslas. A sensor able to detect such magnetic fields with nanometre spatial
      resolution would enable powerful applications, ranging from the detection of
      magnetic resonance signals from individual electron or nuclear spins in complex
      biological molecules to readout of classical or quantum bits of information
      encoded in an electron or nuclear spin memory. Here we experimentally demonstrate
      an approach to such nanoscale magnetic sensing, using coherent manipulation of an
      individual electronic spin qubit associated with a nitrogen-vacancy impurity in
      diamond at room temperature. Using an ultra-pure diamond sample, we achieve
      detection of 3 nT magnetic fields at kilohertz frequencies after 100 s of
      averaging. In addition, we demonstrate a sensitivity of 0.5 muT Hz(-1/2) for a
      diamond nanocrystal with a diameter of 30 nm.

PMID- 18833276
TI  - Nanoscale imaging magnetometry with diamond spins under ambient conditions.
AB  - Magnetic resonance imaging and optical microscopy are key technologies in the
      life sciences. For microbiological studies, especially of the inner workings of
      single cells, optical microscopy is normally used because it easily achieves
      resolution close to the optical wavelength. But in conventional microscopy,
      diffraction limits the resolution to about half the wavelength. Recently, it was
      shown that this limit can be partly overcome by nonlinear imaging techniques, but
      there is still a barrier to reaching the molecular scale. In contrast, in
      magnetic resonance imaging the spatial resolution is not determined by
      diffraction; rather, it is limited by magnetic field sensitivity, and so can in
      principle go well below the optical wavelength. The sensitivity of magnetic
      resonance imaging has recently been improved enough to image single cells, and
      magnetic resonance force microscopy has succeeded in detecting single electrons
      and small nuclear spin ensembles. However, this technique currently requires
      cryogenic temperatures, which limit most potential biological applications.
      Alternatively, single-electron spin states can be detected optically, even at
      room temperature in some systems. Here we show how magneto-optical spin detection
      can be used to determine the location of a spin associated with a single nitrogen
      vacancy centre in diamond with nanometre resolution under ambient conditions. By
      placing these nitrogen-vacancy spins in functionalized diamond nanocrystals,
      biologically specific magnetofluorescent spin markers can be produced.
      Significantly, we show that this nanometre-scale resolution can be achieved
      without any probes located closer than typical cell dimensions. Furthermore, we
      demonstrate the use of a single diamond spin as a scanning probe magnetometer to
      map nanoscale magnetic field variations. The potential impact of single-spin
      imaging at room temperature is far-reaching. It could lead to the capability to
      probe biologically relevant spins in living cells.

PMID- 18833277
TI  - Thresholds for Cenozoic bipolar glaciation.
AB  - The long-standing view of Earth's Cenozoic glacial history calls for the first
      continental-scale glaciation of Antarctica in the earliest Oligocene epoch (
      approximately 33.6 million years ago), followed by the onset of northern
      hemispheric glacial cycles in the late Pliocene epoch, about 31 million years
      later. The pivotal early Oligocene event is characterized by a rapid shift of 1.5
      parts per thousand in deep-sea benthic oxygen-isotope values (Oi-1) within a few
      hundred thousand years, reflecting a combination of terrestrial ice growth and
      deep-sea cooling. The apparent absence of contemporaneous cooling in deep-sea
      Mg/Ca records, however, has been argued to reflect the growth of more ice than
      can be accommodated on Antarctica; this, combined with new evidence of
      continental cooling and ice-rafted debris in the Northern Hemisphere during this
      period, raises the possibility that Oi-1 represents a precursory bipolar
      glaciation. Here we test this hypothesis using an isotope-capable global
      climate/ice-sheet model that accommodates both the long-term decline of Cenozoic
      atmospheric CO(2) levels and the effects of orbital forcing. We show that the
      CO(2) threshold below which glaciation occurs in the Northern Hemisphere (
      approximately 280 p.p.m.v.) is much lower than that for Antarctica (
      approximately 750 p.p.m.v.). Therefore, the growth of ice sheets in the Northern
      Hemisphere immediately following Antarctic glaciation would have required rapid
      CO(2) drawdown within the Oi-1 timeframe, to levels lower than those estimated by
      geochemical proxies and carbon-cycle models. Instead of bipolar glaciation, we
      find that Oi-1 is best explained by Antarctic glaciation alone, combined with
      deep-sea cooling of up to 4 degrees C and Antarctic ice that is less isotopically
      depleted (-30 to -35 per thousand) than previously suggested. Proxy CO(2)
      estimates remain above our model's northern-hemispheric glaciation threshold of
      approximately 280 p.p.m.v. until approximately 25 Myr ago, but have been near or
      below that level ever since. This implies that episodic northern-hemispheric ice
      sheets have been possible some 20 million years earlier than currently assumed
      (although still much later than Oi-1) and could explain some of the variability
      in Miocene sea-level records.

PMID- 18833278
TI  - Crystallographic preferred orientation of akimotoite and seismic anisotropy of
      Tonga slab.
AB  - The mineral akimotoite, ilmenite-structured MgSiO(3), exists at the bottom of the
      Earth's mantle transition zone and within the uppermost lower mantle, especially
      under low-temperature conditions. Akimotoite is thought to be a major constituent
      of the harzburgite layer of subducting slabs, and the most anisotropic mineral in
      the mantle transition zone. It has been predicted that if akimotoite crystals are
      preferentially oriented by plastic deformation, a cold subducted slab would be
      extremely anisotropic. However, there have been no studies of crystallographic
      preferred orientations and very few reports of plastic deformation experiments
      for MgSiO(3) ilmenite. Here we present plastic deformation experiments on
      polycrystalline akimotoite, which were conducted at confining pressures of 20-22
      GPa and temperatures of 1,000-1,300 degrees C. We found a change in
      crystallographic preferred orientation pattern of akimotoite with temperature,
      where the c-axis maximum parallel to the compression direction develops at high
      temperature, whereas the c axes are preferentially oriented parallel to the shear
      direction or perpendicular to the compression direction at lower temperature. The
      previously reported difference in compressional-wave seismic anisotropy between
      the northern and southern segments of the Tonga slab at depths of the mantle
      transition zone can conceivably be attributed to the difference in the
      crystallographic preferred orientation pattern of akimotoite at varying
      temperature within the slab.

PMID- 18833279
TI  - Direct evidence of extensive diversity of HIV-1 in Kinshasa by 1960.
AB  - Human immunodeficiency virus type 1 (HIV-1) sequences that pre-date the
      recognition of AIDS are critical to defining the time of origin and the timescale
      of virus evolution. A viral sequence from 1959 (ZR59) is the oldest known HIV-1
      infection. Other historically documented sequences, important calibration points
      to convert evolutionary distance into time, are lacking, however; ZR59 is the
      only one sampled before 1976. Here we report the amplification and
      characterization of viral sequences from a Bouin's-fixed paraffin-embedded lymph
      node biopsy specimen obtained in 1960 from an adult female in Leopoldville,
      Belgian Congo (now Kinshasa, Democratic Republic of the Congo (DRC)), and we use
      them to conduct the first comparative evolutionary genetic study of early pre
      AIDS epidemic HIV-1 group M viruses. Phylogenetic analyses position this viral
      sequence (DRC60) closest to the ancestral node of subtype A (excluding A2).
      Relaxed molecular clock analyses incorporating DRC60 and ZR59 date the most
      recent common ancestor of the M group to near the beginning of the twentieth
      century. The sizeable genetic distance between DRC60 and ZR59 directly
      demonstrates that diversification of HIV-1 in west-central Africa occurred long
      before the recognized AIDS pandemic. The recovery of viral gene sequences from
      decades-old paraffin-embedded tissues opens the door to a detailed
      palaeovirological investigation of the evolutionary history of HIV-1 that is not
      accessible by other methods.

PMID- 18833280
TI  - Visualizing transient events in amino-terminal autoprocessing of HIV-1 protease.
AB  - HIV-1 protease processes the Gag and Gag-Pol polyproteins into mature structural
      and functional proteins, including itself, and is therefore indispensable for
      viral maturation. The mature protease is active only as a dimer with each subunit
      contributing catalytic residues. The full-length transframe region protease
      precursor appears to be monomeric yet undergoes maturation via intramolecular
      cleavage of a putative precursor dimer, concomitant with the appearance of mature
      like catalytic activity. How such intramolecular cleavage can occur when the
      amino and carboxy termini of the mature protease are part of an intersubunit beta
      sheet located distal from the active site is unclear. Here we visualize the early
      events in N-terminal autoprocessing using an inactive mini-precursor with a four
      residue N-terminal extension that mimics the transframe region protease
      precursor. Using paramagnetic relaxation enhancement, a technique that is
      exquisitely sensitive to the presence of minor species, we show that the mini
      precursor forms highly transient, lowly populated (3-5%) dimeric encounter
      complexes that involve the mature dimer interface but occupy a wide range of
      subunit orientations relative to the mature dimer. Furthermore, the occupancy of
      the mature dimer configuration constitutes a very small fraction of the self
      associated species (accounting for the very low enzymatic activity of the
      protease precursor), and the N-terminal extension makes transient intra- and
      intersubunit contacts with the substrate binding site and is therefore available
      for autocleavage when the correct dimer orientation is sampled within the
      encounter complex ensemble.

PMID- 18833281
TI  - Metabolomics: Biochemistry's new look.

PMID- 18833282
TI  - Metabolomics: Dark matter.

PMID- 18833283
TI  - Metabolomics: Wine-omics.

PMID- 18833286
TI  - A truth serum for cancer--microRNAs have major potential as cancer biomarkers.

PMID- 18833287
TI  - Structure of the intracellular domain of the amyloid precursor protein in complex
      with Fe65-PTB2.
AB  - Cleavage of the amyloid precursor protein (APP) is a crucial event in Alzheimer
      disease pathogenesis that creates the amyloid-beta peptide (Abeta) and liberates
      the carboxy-terminal APP intracellular domain (AICD) into the cytosol. The
      interaction of the APP C terminus with the adaptor protein Fe65 mediates APP
      trafficking and signalling, and is thought to regulate APP processing and Abeta
      generation. We determined the crystal structure of the AICD in complex with the C
      terminal phosphotyrosine-binding (PTB) domain of Fe65. The unique interface
      involves the NPxY PTB-binding motif and two alpha helices. The amino-terminal
      helix of the AICD is capped by threonine T(668), an Alzheimer disease-relevant
      phosphorylation site involved in Fe65-binding regulation. The structure together
      with mutational studies, isothermal titration calorimetry and nuclear magnetic
      resonance experiments sets the stage for understanding T(668) phosphorylation
      dependent complex regulation at a molecular level. A molecular switch model is
      proposed.

PMID- 18833288
TI  - ATM and Chk2 kinase target the p53 cofactor Strap.
AB  - The p53 cofactor Strap (stress responsive activator of p300) is directly targeted
      by the DNA damage signalling pathway where phosphorylation by ATM (ataxia
      telangiectasia mutated) kinase facilitates nuclear accumulation. Here, we show
      that Strap regulation reflects the coordinated interplay between different DNA
      damage-activated protein kinases, ATM and Chk2 (Checkpoint kinase 2), where
      phosphorylation by each kinase provides a distinct functional consequence on the
      activity of Strap. ATM phosphorylation prompts nuclear accumulation, which we
      show occurs by impeding nuclear export, whereas Chk2 phosphorylation augments
      protein stability once Strap has attained a nuclear location. These results
      highlight the various functional roles undertaken by the DNA damage signalling
      kinases in Strap control and, more generally, shed light on the pathways that
      contribute to the regulation of the p53 response.

PMID- 18833289
TI  - Structural and functional analysis of SGT1-HSP90 core complex required for innate
      immunity in plants.
AB  - SGT1 (Suppressor of G2 allele of skp1), a co-chaperone of HSP90 (Heat-shock
      protein 90), is required for innate immunity in plants and animals. Unveiling the
      cross talks between SGT1 and other co-chaperones such as p23, AHA1 (Activator of
      HSP90 ATPase 1) or RAR1 (Required for Mla12 resistance) is an important step
      towards understanding the HSP90 machinery. Nuclear magnetic resonance
      spectroscopy and mutational analyses of HSP90 revealed the nature of its binding
      with the CS domain of SGT1. Although CS is structurally similar to p23, these
      domains were found to non-competitively bind to various regions of HSP90; yet,
      unexpectedly, full-length SGT1 could displace p23 from HSP90. RAR1 partly shares
      the same binding site with HSP90 as the CS domain, whereas AHA1 does not. This
      analysis allowed us to build a structural model of the HSP90-SGT1 complex and to
      obtain a compensatory mutant pair between both partners that is able to restore
      virus resistance in vivo through Rx (Resistance to potato virus X) immune sensor
      stabilization.

PMID- 18833290
TI  - Quantitative analysis of snoRNA association with pre-ribosomes and release of
      snR30 by Rok1 helicase.
AB  - In yeast, three small nucleolar RNAs (snoRNAs) are essential for the processing
      of pre-ribosomal RNA--U3, U14 and snR30--whereas 72 non-essential snoRNAs direct
      site-specific modification of pre-rRNA. We applied a quantitative screen for
      alterations in the pre-ribosome association to all 75 yeast snoRNAs in strains
      depleted of eight putative helicases implicated in 40S subunit synthesis. For the
      modification-guide snoRNAs, we found no clear evidence for the involvement of
      these helicases in the association or dissociation of pre-ribosomes. However, the
      DEAD box helicase Rok1 was required specifically for the release of snR30. Point
      mutations in motif I, but not in motif III, of the helicase domain of Rok1
      impaired the release of snR30, but this was less marked than in strains depleted
      of Rok1, and resulted in a dominant-negative growth phenotype. Dissociation of U3
      and U14 from pre-ribosomes is also dependent on helicases, suggesting that
      release of the essential snoRNAs might differ mechanistically from release of the
      modification-guide snoRNAs.

PMID- 18833291
TI  - Discarding functional residues from the substitution table improves predictions
      of active sites within three-dimensional structures.
AB  - Substitutions of individual amino acids in proteins may be under very different
      evolutionary restraints depending on their structural and functional roles. The
      Environment Specific Substitution Table (ESST) describes the pattern of
      substitutions in terms of amino acid location within elements of secondary
      structure, solvent accessibility, and the existence of hydrogen bonds between
      side chains and neighbouring amino acid residues. Clearly amino acids that have
      very different local environments in their functional state compared to those in
      the protein analysed will give rise to inconsistencies in the calculation of
      amino acid substitution tables. Here, we describe how the calculation of ESSTs
      can be improved by discarding the functional residues from the calculation of
      substitution tables. Four categories of functions are examined in this study:
      protein-protein interactions, protein-nucleic acid interactions, protein-ligand
      interactions, and catalytic activity of enzymes. Their contributions to residue
      conservation are measured and investigated. We test our new ESSTs using the
      program CRESCENDO, designed to predict functional residues by exploiting
      knowledge of amino acid substitutions, and compare the benchmark results with
      proteins whose functions have been defined experimentally. The new methodology
      increases the Z-score by 98% at the active site residues and finds 16% more
      active sites compared with the old ESST. We also find that discarding amino acids
      responsible for protein-protein interactions helps in the prediction of those
      residues although they are not as conserved as the residues of active sites. Our
      methodology can make the substitution tables better reflect and describe the
      substitution patterns of amino acids that are under structural restraints only.

PMID- 18833292
TI  - Removal of AU bias from microarray mRNA expression data enhances computational
      identification of active microRNAs.
AB  - Elucidation of regulatory roles played by microRNAs (miRs) in various biological
      networks is one of the greatest challenges of present molecular and computational
      biology. The integrated analysis of gene expression data and 3'-UTR sequences
      holds great promise for being an effective means to systematically delineate
      active miRs in different biological processes. Applying such an integrated
      analysis, we uncovered a striking relationship between 3'-UTR AU content and gene
      response in numerous microarray datasets. We show that this relationship is
      secondary to a general bias that links gene response and probe AU content and
      reflects the fact that in the majority of current arrays probes are selected from
      target transcript 3'-UTRs. Therefore, removal of this bias, which is in order in
      any analysis of microarray datasets, is of crucial importance when integrating
      expression data and 3'-UTR sequences to identify regulatory elements embedded in
      this region. We developed visualization and normalization schemes for the
      detection and removal of such AU biases and demonstrate that their application to
      microarray data significantly enhances the computational identification of active
      miRs. Our results substantiate that, after removal of AU biases, mRNA expression
      profiles contain ample information which allows in silico detection of miRs that
      are active in physiological conditions.

PMID- 18833293
TI  - Epstein-Barr nuclear antigen 1 contributes to nasopharyngeal carcinoma through
      disruption of PML nuclear bodies.
AB  - Latent Epstein-Barr virus (EBV) infection is strongly associated with several
      cancers, including nasopharyngeal carcinoma (NPC), a tumor that is endemic in
      several parts of the world. We have investigated the molecular basis for how EBV
      latent infection promotes the development of NPC. We show that the viral EBNA1
      protein, previously known to be required to maintain the EBV episomes, also
      causes the disruption of the cellular PML (promyelocytic leukemia) nuclear bodies
      (or ND10s). This disruption occurs both in the context of a native latent
      infection and when exogenously expressed in EBV-negative NPC cells and involves
      loss of the PML proteins. We also show that EBNA1 is partially localized to PML
      nuclear bodies in NPC cells and interacts with a specific PML isoform. PML
      disruption by EBNA1 requires binding to the cellular ubiquitin specific protease,
      USP7 or HAUSP, but is independent of p53. We further observed that p53
      activation, DNA repair and apoptosis, all of which depend on PML nuclear bodies,
      were impaired by EBNA1 expression and that cells expressing EBNA1 were more
      likely to survive after induction of DNA damage. The results point to an
      important role for EBNA1 in the development of NPC, in which EBNA1-mediated
      disruption of PML nuclear bodies promotes the survival of cells with DNA damage.

PMID- 18833294
TI  - B cell recognition of the conserved HIV-1 co-receptor binding site is altered by
      endogenous primate CD4.
AB  - The surface HIV-1 exterior envelope glycoprotein, gp120, binds to CD4 on the
      target cell surface to induce the co-receptor binding site on gp120 as the
      initial step in the entry process. The binding site is comprised of a highly
      conserved region on the gp120 core, as well as elements of the third variable
      region (V3). Antibodies against the co-receptor binding site are abundantly
      elicited during natural infection of humans, but the mechanism of elicitation has
      remained undefined. In this study, we investigate the requirements for
      elicitation of co-receptor binding site antibodies by inoculating rabbits,
      monkeys and human-CD4 transgenic (huCD4) rabbits with envelope glycoprotein (Env)
      trimers possessing high affinity for primate CD4. A cross-species comparison of
      the antibody responses showed that similar HIV-1 neutralization breadth was
      elicited by Env trimers in monkeys relative to wild-type (WT) rabbits. In
      contrast, antibodies against the co-receptor site on gp120 were elicited only in
      monkeys and huCD4 rabbits, but not in the WT rabbits. This was supported by the
      detection of high-titer co-receptor antibodies in all sera from a set derived
      from human volunteers inoculated with recombinant gp120. These findings strongly
      suggest that complexes between Env and (high-affinity) primate CD4 formed in vivo
      are responsible for the elicitation of the co-receptor-site-directed antibodies.
      They also imply that the naive B cell receptor repertoire does not recognize the
      gp120 co-receptor site in the absence of CD4 and illustrate that conformational
      stabilization, imparted by primary receptor interaction, can alter the
      immunogenicity of a type 1 viral membrane protein.

PMID- 18833295
TI  - Molecular mechanisms involved in vascular interactions of the Lyme disease
      pathogen in a living host.
AB  - Hematogenous dissemination is important for infection by many bacterial
      pathogens, but is poorly understood because of the inability to directly observe
      this process in living hosts at the single cell level. All disseminating
      pathogens must tether to the host endothelium despite significant shear forces
      caused by blood flow. However, the molecules that mediate tethering interactions
      have not been identified for any bacterial pathogen except E. coli, which tethers
      to host cells via a specialized pillus structure that is not found in many
      pathogens. Furthermore, the mechanisms underlying tethering have never been
      examined in living hosts. We recently engineered a fluorescent strain of Borrelia
      burgdorferi, the Lyme disease pathogen, and visualized its dissemination from the
      microvasculature of living mice using intravital microscopy. We found that
      dissemination was a multistage process that included tethering, dragging,
      stationary adhesion and extravasation. In the study described here, we used
      quantitative real-time intravital microscopy to investigate the mechanistic
      features of the vascular interaction stage of B. burgdorferi dissemination. We
      found that tethering and dragging interactions were mechanistically distinct from
      stationary adhesion, and constituted the rate-limiting initiation step of
      microvascular interactions. Surprisingly, initiation was mediated by host Fn and
      GAGs, and the Fn- and GAG-interacting B. burgdorferi protein BBK32. Initiation
      was also strongly inhibited by the low molecular weight clinical heparin
      dalteparin. These findings indicate that the initiation of spirochete
      microvascular interactions is dependent on host ligands known to interact in
      vitro with numerous other bacterial pathogens. This conclusion raises the
      intriguing possibility that fibronectin and GAG interactions might be a general
      feature of hematogenous dissemination by other pathogens.

PMID- 18833296
TI  - Identification and functional analysis of antifungal immune response genes in
      Drosophila.
AB  - Essential aspects of the innate immune response to microbial infection appear to
      be conserved between insects and mammals. Although signaling pathways that
      activate NF-kappaB during innate immune responses to various microorganisms have
      been studied in detail, regulatory mechanisms that control other immune responses
      to fungal infection require further investigation. To identify new Drosophila
      genes involved in antifungal immune responses, we selected genes known to be
      differentially regulated in SL2 cells by microbial cell wall components and
      tested their roles in antifungal defense using mutant flies. From 130 mutant
      lines, sixteen mutants exhibited increased sensitivity to fungal infection.
      Examination of their effects on defense against various types of bacteria and
      fungi revealed nine genes that are involved specifically in defense against
      fungal infection. All of these mutants displayed defects in phagocytosis or
      activation of antimicrobial peptide genes following infection. In some mutants,
      these immune deficiencies were attributed to defects in hemocyte development and
      differentiation, while other mutants showed specific defects in immune signaling
      required for humoral or cellular immune responses. Our results identify a new
      class of genes involved in antifungal immune responses in Drosophila.

PMID- 18833297
TI  - Signal peptide-dependent inhibition of MHC class I heavy chain translation by
      rhesus cytomegalovirus.
AB  - The US2-11 region of human and rhesus cytomegalovirus encodes a conserved family
      of glycoproteins that inhibit MHC-I assembly with viral peptides, thus preventing
      cytotoxic T cell recognition. Since HCMV lacking US2-11 is no longer able to
      block assembly and transport of MHC-I, we examined whether this is also observed
      for RhCMV lacking the corresponding region. Unexpectedly, recombinant RhCMV
      lacking US2-11 was still able to inhibit MHC-I expression in infected
      fibroblasts, suggesting the presence of an additional MHC-I evasion mechanism.
      Progressive deletion analysis of RhCMV-specific genomic regions revealed that MHC
      I expression is fully restored upon additional deletion of rh178. The protein
      encoded by this RhCMV-specific open reading frame is anchored in the endoplasmic
      reticulum membrane. In the presence of rh178, RhCMV prevented MHC-I heavy chain
      (HC) expression, but did not inhibit mRNA transcription or association of HC mRNA
      with translating ribosomes. Proteasome inhibitors stabilized a HC degradation
      intermediate in the absence of rh178, but not in its presence, suggesting that
      rh178 prevents completion of HC translation. This interference was signal
      sequence-dependent since replacing the signal peptide with that of CD4 or murine
      HC rendered human HCs resistant to rh178. We have identified an inhibitor of
      antigen presentation encoded by rhesus cytomegalovirus unique in both its lack of
      homology to any other known protein and in its mechanism of action. By preventing
      signal sequence-dependent HC translocation, rh178 acts prior to US2, US3 and US11
      which attack MHC-I proteins after protein synthesis is completed. Rh178 is the
      first viral protein known to interfere at this step of the MHC-I pathway, thus
      taking advantage of the conserved nature of HC leader peptides, and represents a
      new mechanism of translational interference.

PMID- 18833298
TI  - Context-dependent requirement for dE2F during oncogenic proliferation.
AB  - The Hippo pathway negatively regulates the cell number in epithelial tissue. Upon
      its inactivation, an excess of cells is produced. These additional cells are
      generated from an increased rate of cell division, followed by inappropriate
      proliferation of cells that have failed to exit the cell cycle. We analyzed the
      consequence of inactivation of the entire E2F family of transcription factors in
      these two settings. In Drosophila, there is a single activator, dE2F1, and a
      single repressor, dE2F2, which act antagonistically to each other during
      development. While the loss of the activator dE2F1 results in a severe impairment
      in cell proliferation, this defect is rescued by the simultaneous loss of the
      repressor dE2F2, as cell proliferation occurs relatively normally in the absence
      of both dE2F proteins. We found that the combined inactivation of dE2F1 and dE2F2
      had no significant effect on the increased rate of cell division of Hippo pathway
      mutant cells. In striking contrast, inappropriate proliferation of cells that
      failed to exit the cell cycle was efficiently blocked. Furthermore, our data
      suggest that such inappropriate proliferation was primarily dependent on the
      activator, de2f1, as loss of de2f2 was inconsequential. Consistently, Hippo
      pathway mutant cells had elevated E2F activity and induced dE2F1 expression at a
      point when wild-type cells normally exit the cell cycle. Thus, we uncovered a
      critical requirement for the dE2F family during inappropriate proliferation of
      Hippo pathway mutant cells.

PMID- 18833299
TI  - Zebrafish eda and edar mutants reveal conserved and ancestral roles of
      ectodysplasin signaling in vertebrates.
AB  - The genetic basis of the development and variation of adult form of vertebrates
      is not well understood. To address this problem, we performed a mutant screen to
      identify genes essential for the formation of adult skeletal structures of the
      zebrafish. Here, we describe the phenotypic and molecular characterization of a
      set of mutants showing loss of adult structures of the dermal skeleton, such as
      the rays of the fins and the scales, as well as the pharyngeal teeth. The
      mutations represent adult-viable, loss of function alleles in the ectodysplasin
      (eda) and ectodysplasin receptor (edar) genes. These genes are frequently mutated
      in the human hereditary disease hypohidrotic ectodermal dysplasia (HED; OMIM
      224900, 305100) that affects the development of integumentary appendages such as
      hair and teeth. We find mutations in zebrafish edar that affect similar residues
      as mutated in human cases of HED and show similar phenotypic consequences. eda
      and edar are not required for early zebrafish development, but are rather
      specific for the development of adult skeletal and dental structures. We find
      that the defects of the fins and scales are due to the role of Eda signaling in
      organizing epidermal cells into discrete signaling centers of the scale epidermal
      placode and fin fold. Our genetic analysis demonstrates dose-sensitive and organ
      specific response to alteration in levels of Eda signaling. In addition, we show
      substantial buffering of the effect of loss of edar function in different genetic
      backgrounds, suggesting canalization of this developmental system. We uncover a
      previously unknown role of Eda signaling in teleosts and show conservation of the
      developmental mechanisms involved in the formation and variation of both
      integumentary appendages and limbs. Lastly, our findings point to the utility of
      adult genetic screens in the zebrafish in identifying essential developmental
      processes involved in human disease and in morphological evolution.

PMID- 18833300
TI  - High-throughput phenotypic characterization of Pseudomonas aeruginosa membrane
      transport genes.
AB  - The deluge of data generated by genome sequencing has led to an increasing
      reliance on bioinformatic predictions, since the traditional experimental
      approach of characterizing gene function one at a time cannot possibly keep pace
      with the sequence-based discovery of novel genes. We have utilized Biolog
      phenotype MicroArrays to identify phenotypes of gene knockout mutants in the
      opportunistic pathogen and versatile soil bacterium Pseudomonas aeruginosa in a
      relatively high-throughput fashion. Seventy-eight P. aeruginosa mutants defective
      in predicted sugar and amino acid membrane transporter genes were screened and
      clear phenotypes were identified for 27 of these. In all cases, these phenotypes
      were confirmed by independent growth assays on minimal media. Using qRT-PCR, we
      demonstrate that the expression levels of 11 of these transporter genes were
      induced from 4- to 90-fold by their substrates identified via phenotype analysis.
      Overall, the experimental data showed the bioinformatic predictions to be largely
      correct in 22 out of 27 cases, and led to the identification of novel transporter
      genes and a potentially new histamine catabolic pathway. Thus, rapid phenotype
      identification assays are an invaluable tool for confirming and extending
      bioinformatic predictions.

PMID- 18833301
TI  - A Myo6 mutation destroys coordination between the myosin heads, revealing new
      functions of myosin VI in the stereocilia of mammalian inner ear hair cells.
AB  - Myosin VI, found in organisms from Caenorhabditis elegans to humans, is essential
      for auditory and vestibular function in mammals, since genetic mutations lead to
      hearing impairment and vestibular dysfunction in both humans and mice. Here, we
      show that a missense mutation in this molecular motor in an ENU-generated mouse
      model, Tailchaser, disrupts myosin VI function. Structural changes in the
      Tailchaser hair bundles include mislocalization of the kinocilia and branching of
      stereocilia. Transfection of GFP-labeled myosin VI into epithelial cells and
      delivery of endocytic vesicles to the early endosome revealed that the mutant
      phenotype displays disrupted motor function. The actin-activated ATPase rates
      measured for the D179Y mutation are decreased, and indicate loss of coordination
      of the myosin VI heads or 'gating' in the dimer form. Proper coordination is
      required for walking processively along, or anchoring to, actin filaments, and is
      apparently destroyed by the proximity of the mutation to the nucleotide-binding
      pocket. This loss of myosin VI function may not allow myosin VI to transport its
      cargoes appropriately at the base and within the stereocilia, or to anchor the
      membrane of stereocilia to actin filaments via its cargos, both of which lead to
      structural changes in the stereocilia of myosin VI-impaired hair cells, and
      ultimately leading to deafness.

PMID- 18833302
TI  - Time-lapse analysis and mathematical characterization elucidate novel mechanisms
      underlying muscle morphogenesis.
AB  - Skeletal muscle morphogenesis transforms short muscle precursor cells into long,
      multinucleate myotubes that anchor to tendons via the myotendinous junction
      (MTJ). In vertebrates, a great deal is known about muscle specification as well
      as how somitic cells, as a cohort, generate the early myotome. However, the
      cellular mechanisms that generate long muscle fibers from short cells and the
      molecular factors that limit elongation are unknown. We show that zebrafish fast
      muscle fiber morphogenesis consists of three discrete phases: short precursor
      cells, intercalation/elongation, and boundary capture/myotube formation. In the
      first phase, cells exhibit randomly directed protrusive activity. The second
      phase, intercalation/elongation, proceeds via a two-step process: protrusion
      extension and filling. This repetition of protrusion extension and filling
      continues until both the anterior and posterior ends of the muscle fiber reach
      the MTJ. Finally, both ends of the muscle fiber anchor to the MTJ (boundary
      capture) and undergo further morphogenetic changes as they adopt the
      stereotypical, cylindrical shape of myotubes. We find that the basement membrane
      protein laminin is required for efficient elongation, proper fiber orientation,
      and boundary capture. These early muscle defects in the absence of either
      lamininbeta1 or laminingamma1 contrast with later dystrophic phenotypes in
      lamininalpha2 mutant embryos, indicating discrete roles for different laminin
      chains during early muscle development. Surprisingly, genetic mosaic analysis
      suggests that boundary capture is a cell-autonomous phenomenon. Taken together,
      our results define three phases of muscle fiber morphogenesis and show that the
      critical second phase of elongation proceeds by a repetitive process of
      protrusion extension and protrusion filling. Furthermore, we show that laminin is
      a novel and critical molecular cue mediating fiber orientation and limiting
      muscle cell length.

PMID- 18833303
TI  - Mutability and importance of a hypermutable cell subpopulation that produces
      stress-induced mutants in Escherichia coli.
AB  - In bacterial, yeast, and human cells, stress-induced mutation mechanisms are
      induced in growth-limiting environments and produce non-adaptive and adaptive
      mutations. These mechanisms may accelerate evolution specifically when cells are
      maladapted to their environments, i.e., when they are are stressed. One mechanism
      of stress-induced mutagenesis in Escherichia coli occurs by error-prone DNA
      double-strand break (DSB) repair. This mechanism was linked previously to a
      differentiated subpopulation of cells with a transiently elevated mutation rate,
      a hypermutable cell subpopulation (HMS). The HMS could be important, producing
      essentially all stress-induced mutants. Alternatively, the HMS was proposed to
      produce only a minority of stress-induced mutants, i.e., it was proposed to be
      peripheral. We characterize three aspects of the HMS. First, using improved
      mutation-detection methods, we estimate the number of mutations per genome of HMS
      derived cells and find that it is compatible with fitness after the HMS state.
      This implies that these mutants are not necessarily an evolutionary dead end, and
      could contribute to adaptive evolution. Second, we show that stress-induced
      Lac(+) mutants, with and without evidence of descent from the HMS, have similar
      Lac(+) mutation sequences. This provides evidence that HMS-descended and most
      stress-induced mutants form via a common mechanism. Third, mutation-stimulating
      DSBs introduced via I-SceI endonuclease in vivo do not promote Lac(+) mutation
      independently of the HMS. This and the previous finding support the hypothesis
      that the HMS underlies most stress-induced mutants, not just a minority of them,
      i.e., it is important. We consider a model in which HMS differentiation is
      controlled by stress responses. Differentiation of an HMS potentially limits the
      risks of mutagenesis in cell clones.

PMID- 18833304
TI  - Mutation and evolutionary rates in adelie penguins from the antarctic.
AB  - Precise estimations of molecular rates are fundamental to our understanding of
      the processes of evolution. In principle, mutation and evolutionary rates for
      neutral regions of the same species are expected to be equal. However, a number
      of recent studies have shown that mutation rates estimated from pedigree material
      are much faster than evolutionary rates measured over longer time periods. To
      resolve this apparent contradiction, we have examined the hypervariable region
      (HVR I) of the mitochondrial genome using families of Adelie penguins (Pygoscelis
      adeliae) from the Antarctic. We sequenced 344 bps of the HVR I from penguins
      comprising 508 families with 915 chicks, together with both their parents. All of
      the 62 germline heteroplasmies that we detected in mothers were also detected in
      their offspring, consistent with maternal inheritance. These data give an
      estimated mutation rate (micro) of 0.55 mutations/site/Myrs (HPD 95% confidence
      interval of 0.29-0.88 mutations/site/Myrs) after accounting for the persistence
      of these heteroplasmies and the sensitivity of current detection methods. In
      comparison, the rate of evolution (k) of the same HVR I region, determined using
      DNA sequences from 162 known age sub-fossil bones spanning a 37,000-year period,
      was 0.86 substitutions/site/Myrs (HPD 95% confidence interval of 0.53 and 1.17).
      Importantly, the latter rate is not statistically different from our estimate of
      the mutation rate. These results are in contrast to the view that molecular rates
      are time dependent.

PMID- 18833305
TI  - Anatomic alignment, menstrual cycle phase, and the risk of anterior cruciate
      ligament injury.

PMID- 18833306
TI  - ACL injury in the female athlete: a multifactorial problem that remains poorly
      understood.

PMID- 18833307
TI  - Return of postural control to baseline after anaerobic and aerobic exercise
      protocols.
AB  - CONTEXT: With regard to sideline concussion testing, the effect of fatigue
      associated with different types of exercise on postural control is unknown.
      OBJECTIVE: To evaluate the effects of fatigue on postural control in healthy
      college-aged athletes performing anaerobic and aerobic exercise protocols and to
      establish an immediate recovery time course from each exercise protocol for
      postural control measures to return to baseline status. DESIGN: Counterbalanced,
      repeated measures. SETTING: Research laboratory. PATIENTS OR OTHER PARTICIPANTS:
      Thirty-six collegiate athletes (18 males, 18 females; age = 19.00 +/- 1.01 years,
      height = 172.44 +/- 10.47 cm, mass = 69.72 +/- 12.84 kg). INTERVENTION(S):
      Participants completed 2 counterbalanced sessions within 7 days. Each session
      consisted of 1 exercise protocol followed by postexercise measures of postural
      control taken at 3-, 8-, 13-, and 18-minute time intervals. Baseline measures
      were established during the first session, before the specified exertion protocol
      was performed. MAIN OUTCOME MEASURE(S): Balance Error Scoring System (BESS)
      results, sway velocity, and elliptical sway area. RESULTS: We found a decrease in
      postural control after each exercise protocol for all dependent measures. An
      interaction was noted between exercise protocol and time for total BESS score (P
      = .002). For both exercise protocols, all measures of postural control returned
      to baseline within 13 minutes. CONCLUSIONS: Postural control was negatively
      affected after anaerobic and aerobic exercise protocols as measured by total BESS
      score, elliptical sway area, and sway velocity. The effect of exertion lasted up
      to 13 minutes after each exercise was completed. Certified athletic trainers and
      clinicians should be aware of these effects and their recovery time course when
      determining an appropriate time to administer sideline assessments of postural
      control after a suspected mild traumatic brain injury.

PMID- 18833308
TI  - Electromyography of 3 scapular muscles: a comparative analysis of the cuff link
      device and a standard push-up.
AB  - CONTEXT: The Cuff Link is a closed kinetic chain rehabilitation apparatus for the
      upper extremity. Limited research has established its effectiveness to elicit
      muscle activation of the scapular muscles. OBJECTIVE: To determine if scapular
      muscle activation differs in response to 2 upper extremity closed kinetic chain
      exercises: Cuff Link and standard push-up. DESIGN: A single-group, repeated
      measures design. SETTING: Controlled laboratory. PATIENTS OR OTHER PARTICIPANTS:
      Twenty-eight healthy individuals (13 women: age = 19.69 +/- 1.55 years, height =
      167.44 +/- 9.52 cm, mass = 61.00 +/- 8.79 kg; 15 men: age = 22.00 +/- 3.91 years,
      height = 181.44 +/- 6.60 cm, mass = 82.36 +/- 13.23 kg) with no history of
      shoulder or low back injury volunteered to participate in this study.
      INTERVENTION(S): Participants performed 10 trials of complete revolutions on the
      Cuff Link and 10 full-weight-bearing push-ups. We controlled trial velocity and
      randomized order. Trunk and shoulder positions were normalized to the
      participant's height. Using surface electromyography, we recorded muscle activity
      of the serratus anterior, middle trapezius, and lower trapezius. Rectified and
      smoothed electromyography data for the serratus anterior, middle trapezius, and
      lower trapezius were normalized as a percentage of the maximal voluntary
      isometric contractions (%MVIC). MAIN OUTCOME MEASURE(S): Mean muscle activity of
      the serratus anterior, middle trapezius, and lower trapezius. We used paired
      samples t tests to analyze the mean data for each condition. The alpha level was
      adjusted to .016 to avoid a type I error. RESULTS: Middle trapezius %MVIC was
      greater during push-ups (27.01 +/- 20.40%) than during use of the Cuff Link
      (11.49 +/- 9.46%) (P = .001). Lower trapezius %MVIC was greater during push-ups
      (36.07 +/- 18.99%) than during use of the Cuff Link (16.29 +/- 8.64%) (P = .001).
      There was no difference in %MVIC for the serratus anterior between conditions.
      CONCLUSIONS: The push-up demonstrated greater middle trapezius and lower
      trapezius activation levels compared with the Cuff Link. However, the push-up had
      a high participant failure rate. Because serratus anterior activation levels were
      similar, the Cuff Link may be an appropriate alternative for individuals lacking
      the upper body strength to perform a push-up.

PMID- 18833309
TI  - Reliability limits of the modified Thomas test for assessing rectus femoris
      muscle flexibility about the knee joint.
AB  - CONTEXT: The modified Thomas test is commonly used in the clinical setting to
      assess flexibility about the thigh region. OBJECTIVE: To evaluate the clinical
      reliability of the modified Thomas test for evaluating the flexibility of the
      rectus femoris muscle about the knee joint. DESIGN: Descriptive laboratory study
      using a test-retest design. SETTING: Institution-based clinical orthopaedic
      setting. PATIENTS OR OTHER PARTICIPANTS: Fifty-seven individuals between the ages
      of 18 and 45 years with no history of trauma participated. Of those, 54 completed
      the study. INTERVENTION(S): Three Board-certified athletic therapists with an
      average of 12.67 years of sport medicine expertise assessed rectus femoris
      flexibility using pass/fail and goniometer scoring systems. A retest session was
      completed 7 to 10 days later. MAIN OUTCOME MEASURE(S): Parametric and
      nonparametric tests were used to compare participants' test-retest results.
      RESULTS: Chance-corrected kappa values (intrarater x = 0.40, 95% confidence
      interval [CI] = 0.30, 0.54; interrater x = 0.33, 95% CI = 0.23, 0.41) indicated
      generally poor levels of reliability for pass/fail scoring. Intraclass
      correlation coefficient (ICC) values (intrarater x = 0.67, 95% CI = 0.55, 0.76;
      interrater x = 0.50, 95% CI = 0.40, 0.60) indicated fair to moderate levels of
      reliability for goniometer data. Measurement error values (standard error of
      measurement = 7 degrees , method error = 6 degrees , and coefficient of variation
      = 13%) and Bland-Altman plots (with 95% limits of agreement) further demonstrated
      the degree of intrarater variance for each examiner when conducting the test.
      CONCLUSIONS: These results call into question the statistical reliability of the
      modified Thomas test and provide clinicians with important information regarding
      its reliability limits when used to clinically assess flexibility of the rectus
      femoris muscle about the knee joint in a physically active population. More
      research is needed to ascertain the variables that may confound the statistical
      reliability of this orthopaedic technique.

PMID- 18833310
TI  - A biomechanical investigation of a single-limb squat: implications for lower
      extremity rehabilitation exercise.
AB  - CONTEXT: Single-limb squats on a decline angle have been suggested as a
      rehabilitative intervention to target the knee extensors. Investigators, however,
      have presented very little empirical research in which they have documented the
      biomechanics of these exercises or have determined the optimum angle of decline
      used. OBJECTIVE: To determine the involvement of the gastrocnemius and rectus
      femoris muscles and the external ankle and knee joint moments at 60 degrees of
      knee flexion while performing a single-limb squat at different decline angles.
      DESIGN: Participants acted as their own controls in a repeated-measures design.
      PATIENTS OR OTHER PARTICIPANTS: We recruited 10 participants who had no pain,
      injury, or neurologic disorder. INTERVENTION(S): Participants performed single
      limb squats at different decline angles. MAIN OUTCOME MEASURE(S): Angle-specific
      knee and ankle moments were calculated at 60 degrees of knee flexion. Angle
      specific electromyography (EMG) activity was calculated at 60 degrees of knee
      flexion. Integrated EMG also was calculated to determine the level of muscle
      activity over the entire squat. RESULTS: An increase was seen in the knee moments
      (P < .05) and integrated EMG in the rectus femoris (P < .001) as the decline
      angle increased. A decrease was seen in the ankle moments as the decline angle
      increased (P = .001), but EMG activity in the gastrocnemius increased between 16
      degrees and 24 degrees (P = .018). CONCLUSIONS: As the decline angle increased,
      the knee extensor moment and EMG activity increased. As the decline angle
      increased, the ankle plantar-flexor moments decreased; however, an increase in
      the EMG activity was seen with the 24 degrees decline angle compared with the 16
      degrees decline angle. This indicates that decline squats at an angle greater
      than 16 degrees may not reduce passive calf tension, as was suggested previously,
      and may provide no mechanical advantage for the knee.

PMID- 18833311
TI  - Initial reliability of the Standardized Orthopedic Assessment Tool (SOAT).
AB  - CONTEXT: Orthopaedic assessment skills are critical to the success of athletic
      therapists and trainers. The Standardized Orthopedic Assessment Tool (SOAT) has
      been content validated. OBJECTIVE: To establish interrater reliability of the
      SOAT. PATIENTS OR OTHER PARTICIPANTS: Thirty-two college students, 10 raters, and
      2 standardized patients (SPs) from Calgary, Alberta, Canada. DESIGN: Randomized
      observational study. INTERVENTION(S): Students were allowed 30 minutes to
      complete a mock orthopaedic assessment of an SP with an injury specific to a
      region of the body (shoulder, knee, or ankle). Using the region-specific SOAT,
      raters and SPs evaluated students' orthopaedic assessment skills. MAIN OUTCOME
      MEASURE(S): The sum totals of the SOAT for 2 raters and 1 SP were used to
      calculate each student's performance scores for respective scenarios. Scale
      reliability analysis (Cronbach alpha) was completed on the SOAT for each of the 3
      body-region examinations. RESULTS: The mean overall reliability of 3 SOATs (ie,
      ankle, knee, and shoulder) was positive: alpha = .85 with the SP scores factored
      into the equation and alpha = .86 without the SP scores factored into the
      equation. Reliability for the ankle region was highest (alpha = .91), followed by
      the knee (alpha = .83) and the shoulder (alpha = .82). CONCLUSIONS: The study
      sample size was small, but the results will enable further study with
      generalization to a broader audience of athletic therapists and athletic
      trainers. Because a baseline measure of reliability was established using a
      robust statistical analysis, future researchers can employ more stringent
      statistical analysis and focus on the effects of various pedagogical techniques
      to teach and learn the underlying construct of clinical competence in orthopaedic
      assessment.

PMID- 18833312
TI  - Nutrition concepts for elite distance runners based on macronutrient and energy
      expenditure.
AB  - CONTEXT: Elite distance runners (EDR) must optimize their nutrition to maintain
      their demanding training schedules. OBJECTIVE: To develop a nutrition concept for
      EDR based on energy and macronutrient expenditures. DESIGN: This theoretical
      study provides calculations for macronutrient and energy expenditures of EDR.
      Anthropometric and metabolic characteristics of EDR were assumed based on average
      real EDR. SETTING: University of Kiel. PATIENTS OR OTHER PARTICIPANTS: Three
      prototypic types of male EDR described in the literature as type I (TI; body mass
      = 72 kg, respiratory quotient = 0.9 at rest, fast-twitch muscle fibers = 60% to
      70%), type II (TII; body mass = 67 kg, respiratory quotient = 0.82 at rest, fast
      twitch muscle fibers = 50%), and type III (TIII; body mass = 60 kg, respiratory
      quotient = 0.75 at rest, fast-twitch muscle fibers = 30% to 40%). MAIN OUTCOME
      MEASURE(S): We calculated the macronutrient and energy expenditures of the 3
      types of EDR according to body mass, respiratory quotient, and percentage of fast
      twitch muscle fibers. RESULTS: We found that the average energy expenditure was
      3750 kcal . d(-1) for TI runners, 3463 kcal . d(-1) for TII runners, and 3079
      kcal . d(-1) for TIII runners. The carbohydrate (CHO) expenditure reached an
      average value of 10.0 g . kg(-1) . d(-1) for TI runners, 8.0 g . kg(-1) . d(-1)
      for TII runners, and 4.7 g . kg(-1) . d(-1) for TIII runners. When the EDR
      accomplished running sessions at a pace >or=100% of maximum oxygen consumption,
      all types of runners had a CHO demand of about 10 g . kg(-1) . d(-1). The TI and
      TII runners need a CHO intake of 8 to 10 g . kg(-1) . d(-1). For the TIII
      runners, a CHO intake >6 g . kg(-1) . d(-1) is necessary during anaerobic
      training sessions. CONCLUSIONS: Nutrition concepts must be differentiated for EDR
      according to metabolic and anthropometric characteristics of the runners and
      their special training emphases.

PMID- 18833313
TI  - Work-family conflict, part I: Antecedents of work-family conflict in national
      collegiate athletic association division I-A certified athletic trainers.
AB  - CONTEXT: Work-family conflict (WFC) involves discord that arises when the demands
      of work interfere with the demands of family or home life. Long work hours,
      minimal control over work schedules, and time spent away from home are
      antecedents to WFC. To date, few authors have examined work-family conflict
      within the athletic training profession. OBJECTIVE: To investigate the occurrence
      of WFC in certified athletic trainers (ATs) and to identify roots and factors
      leading to quality-of-life issues for ATs working in the National Collegiate
      Athletic Association Division I-A setting. DESIGN: Survey questionnaire and
      follow-up, in-depth, in-person interviews. SETTING: Division I-A universities
      sponsoring football. PATIENTS OR OTHER PARTICIPANTS: A total of 587 ATs (324 men,
      263 women) responded to the questionnaire. Twelve ATs (6 men, 6 women)
      participated in the qualitative portion: 2 head ATs, 4 assistant ATs, 4 graduate
      assistant ATs, and 2 AT program directors. DATA COLLECTION AND ANALYSIS: Multiple
      regression analysis was performed to determine whether workload and travel
      predicted levels of WFC. Analyses of variance were calculated to investigate
      differences among the factors of sex, marital status, and family status.
      Interviews were transcribed verbatim and then analyzed using computer software as
      well as member checks and peer debriefing. The triangulation of the data
      collection and multiple sources of qualitative analysis were utilized to limit
      potential researcher prejudices. RESULTS: Regression analyses revealed that long
      work hours and travel directly contributed to WFC. In addition to long hours and
      travel, inflexible work schedules and staffing patterns were discussed by the
      interview participants as antecedents to WFC. Regardless of sex (P = .142),
      marital status (P = .687), family status (P = .055), or age of children (P =
      .633), WFC affected Division I-A ATs. CONCLUSIONS: No matter their marital or
      family status, ATs employed at the Division I-A level experienced difficulties
      balancing their work and home lives. Sources of conflict primarily stemmed from
      the consuming nature of the profession, travel, inflexible work schedules, and
      lack of full-time staff members.

PMID- 18833314
TI  - Work-family conflict, part II: Job and life satisfaction in national collegiate
      athletic association division I-A certified athletic trainers.
AB  - CONTEXT: Previous researchers have shown that work-family conflict (WFC) affects
      the level of a person's job satisfaction, life satisfaction, and job burnout and
      intentions to leave the profession. However, WFC and its consequences have not
      yet been fully investigated among certified athletic trainers. OBJECTIVE: To
      investigate the relationship between WFC and various outcome variables among
      certified athletic trainers working in National Collegiate Athletic Association
      Division I-A settings. DESIGN: A mixed-methods design using a 53-item survey
      questionnaire and follow-up in-depth interviews was used to examine the
      prevalence of WFC. SETTING: Division I-A universities sponsoring football.
      PATIENTS OR OTHER PARTICIPANTS: A total of 587 athletic trainers (324 men, 263
      women) responded to the questionnaire, and 12 (6 men, 6 women) participated in
      the qualitative portion of the mixed-methods study. DATA COLLECTION AND ANALYSIS:
      We calculated Pearson correlations to determine the relationship between WFC and
      job satisfaction, life satisfaction, and job burnout. Regression analyses were
      run to determine whether WFC was a predictor of job satisfaction, job burnout, or
      intention to leave the profession. Interviews were transcribed verbatim and then
      analyzed using the computer program N6 as well as member checks and peer
      debriefing. RESULTS: Negative relationships were found between WFC and job
      satisfaction (r = -.52, P < .001). Positive were noted between WFC and job
      burnout (r = .63, P < .001) and intention to leave the profession (r = .46, P <
      .001). Regression analyses revealed that WFC directly contributed to job
      satisfaction (P < .001), job burnout (P < .001), and intention to leave the
      profession (P < .001). CONCLUSIONS: Overall, our findings concur with those of
      previous researchers on WFC and its negative relationships to job satisfaction
      and life satisfaction and positive relationship to job burnout and intention to
      leave an organization. Sources of WFC, such as time, inflexible work schedules,
      and inadequate staffing, were also related to job burnout and job dissatisfaction
      in this population.

PMID- 18833316
TI  - Research Retreat IV: ACL injuries--the gender bias: April 3-5, 2008 Greensboro,
      NC.

PMID- 18833315
TI  - Ankle ligament healing after an acute ankle sprain: an evidence-based approach.
AB  - OBJECTIVE: To perform a systematic review to determine the healing time of the
      lateral ankle ligaments after an acute ankle sprain. DATA SOURCES: We identified
      English-language research studies from 1964 to 2007 by searching MEDLINE,
      Physiotherapy Evidence Database (PEDro), SportDiscus, and CINAHL using the terms
      ankle sprain, ankle rehabilitation, ankle injury, ligament healing, and
      immobilization. STUDY SELECTION: We selected studies that described randomized,
      controlled clinical trials measuring ligament laxity either objectively or
      subjectively immediately after injury and at least 1 more time after injury. DATA
      EXTRACTION: Two reviewers independently scored the 7 studies that met the
      inclusion criteria. Because of differences in study designs, a meta-analysis
      could not be performed. Effect sizes and confidence intervals could be calculated
      only for 1 study. The percentages of subjective and objective instability were
      calculated for the remaining studies. DATA SYNTHESIS: Ankle laxity improved over
      a period of 6 weeks to 1 year. One author showed stress talar tilt values of
      16.10 +/- 8.8 degrees immediately after injury and 3.4 +/- 3.6 degrees at 3
      months after injury. In 2 articles, the authors reported that positive anterior
      drawer tests were still present in 3% to 31% of participants at 6 months after
      injury. Additionally, feelings of instability affected 7% to 42% of participants
      up to 1 year after injury. CONCLUSIONS/RECOMMENDATIONS: In the studies that we
      examined, it took at least 6 weeks to 3 months before ligament healing occurred.
      However, at 6 weeks to 1 year after injury, a large percentage of participants
      still had objective mechanical laxity and subjective ankle instability. Direct
      comparison among articles is difficult because of differences in methods. More
      research focusing on more reliable methods of measuring ankle laxity is needed so
      that clinicians can know how long ligament healing takes after injury. This
      knowledge will help clinicians to make better decisions during rehabilitation and
      for return to play.

PMID- 18833317
TI  - Neuromuscular and biomechanical factors.

PMID- 18833318
TI  - Anatomical and structural factors.

PMID- 18833319
TI  - Hormonal factors.

PMID- 18833320
TI  - Risk factor screening and prevention.

PMID- 18833321
TI  - The ACL injury enigma: we can't prevent what we don't understand.

PMID- 18833322
TI  - Quantitative modeling of currents from a voltage gated ion channel undergoing
      fast inactivation.
AB  - Ion channels play a central role in setting gradients of ion concentration and
      electrostatic potentials, which in turn regulate sensory systems and other
      functions. Based on the structure of the open configuration of the Kv1.2 channel
      and the suggestion that the two ends of the N-terminal inactivating peptide form
      a bivalent complex that simultaneously blocks the channel pore and binds to the
      cytoplasmic T1 domain, we propose a six state kinetic model that for the first
      time reproduces the kinetics of recovery of the Drosophila Shaker over the full
      range of time scales and hyperpolarization potentials, including tail currents.
      The model is motivated by a normal mode analysis of the inactivated channel that
      suggests that a displacement consistent with models of the closed state
      propagates to the T1 domain via the S1-T1 linker. This motion stretches the bound
      (inactivating) peptide, hastening the unblocking of the pore. This pulling force
      is incorporated into the rates of the open to blocked states, capturing the fast
      recovery phase of the current for repolarization events shorter than 1 ms. If the
      membrane potential is hyperpolarized, essential dynamics further suggests that
      the T1 domain returns to a configuration where the peptide is un-stretched and
      the S1-T1 linker is extended. Coupling this novel hyperpolarized substate to the
      closed, open and blocked pore states is enough to quantitatively estimate the
      number of open channels as a function of time and membrane potential. A
      straightforward prediction of the model is that a slow ramping of the potential
      leads to very small currents.

PMID- 18833323
TI  - Cellular mechanisms underlying the laxative effect of flavonol naringenin on rat
      constipation model.
AB  - BACKGROUND & AIMS: Symptoms of constipation are extremely common, especially in
      the elderly. The present study aim to identify an efficacious treatment strategy
      for constipation by evaluating the secretion-promoting and laxative effect of a
      herbal compound, naringenin, on intestinal epithelial anion secretion and a rat
      constipation model, respectively. METHODS/PRINCIPAL FINDINGS: In isolated rat
      colonic crypts, mucosal addition of naringenin (100 microM) elicited a
      concentration-dependent and sustained increase in the short-circuit current
      (I(SC)), which could be inhibited in Cl- free solution or by bumetanide and DPC
      (diphenylamine-2-carboxylic acid), but not by DIDS (4, 4'-
      diisothiocyanatostilbene-2, 2'-disulfonic acid). Naringenin could increase
      intracellular cAMP content and PKA activity, consisted with that MDL-12330A (N
      (Cis-2-phenyl-cyclopentyl) azacyclotridecan-2-imine-hydrochloride) pretreatment
      reduced the naringenin-induced I(SC). In addition, significant inhibition of the
      naringenin-induced I(SC) by quinidine indicated that basolateral K+ channels were
      involved in maintaining this cAMP-dependent Cl- secretion. Naringenin-evoked
      whole cell current which exhibited a linear I-V relationship and time-and voltage
      independent characteristics was inhibited by DPC, indicating that the cAMP
      activated Cl- conductance most likely CFTR (cystic fibrosis transmembrane
      conductance regulator) was involved. In rat constipation model, administration of
      naringenin restored the level of fecal output, water content and mucus secretion
      compared to loperamide-administrated group. CONCLUSIONS: Taken together, our data
      suggest that naringenin could stimulate Cl- secretion in colonic epithelium via a
      signaling pathway involving cAMP and PKA, hence provide an osmotic force for
      subsequent colonic fluid secretion by which the laxative effect observed in the
      rat constipation model. Naringenin appears to be a novel alternative treatment
      strategy for constipation.

PMID- 18833324
TI  - Loss of cannabinoid receptor CB1 induces preterm birth.
AB  - BACKGROUND: Preterm birth accounting approximate 10% of pregnancies in women is a
      tremendous social, clinical and economic burden. However, its underlying causes
      remain largely unknown. Emerging evidence suggests that endocannabinoid signaling
      via cannabinoid receptor CB1 play critical roles in multiple early pregnancy
      events in both animals and humans. Since our previous studies demonstrated that
      loss of CB1 defers the normal implantation window in mice, we surmised that CB1
      deficiency would influence parturition events. METHODS AND FINDINGS: Exploiting
      mouse models with targeted deletion of Cnr1, Cnr2 and Ptgs1 encoding CB1, CB2 and
      cyclooxygenase-1, respectively, we examined consequences of CB1 or CB2 silencing
      on the onset of parturition. We observed that genetic or pharmacological
      inactivation of CB1, but not CB2, induced preterm labor in mice. Radioimmunoassay
      analysis of circulating levels of ovarian steroid hormones revealed that
      premature birth resulting from CB1 inactivation is correlated with altered
      progesterone/estrogen ratios prior to parturition. More strikingly, the
      phenotypic defects of prolonged pregnancy length and parturition failure in mice
      missing Ptgs1 were corrected by introducing CB1 deficiency into Ptgs1 null mice.
      In addition, loss of CB1 resulted in aberrant secretions of corticotrophin
      releasing hormone and corticosterone during late gestation. The
      pathophysiological significance of this altered corticotrophin-releasing hormone
      driven endocrine activity in the absence of CB1 was evident from our subsequent
      findings that a selective corticotrophin-releasing hormone antagonist was able to
      restore the normal parturition timing in Cnr1 deficient mice. In contrast, wild
      type females receiving excessive levels of corticosterone induced preterm birth.
      CONCLUSIONS: CB1 deficiency altering normal progesterone and estrogen levels
      induces preterm birth in mice. This defect is independent of prostaglandins
      produced by cyclooxygenase-1. Moreover, CB1 inactivation resulted in aberrant
      corticotrophin-releasing hormone and corticosterone activities prior to
      parturition, suggesting that CB1 regulates labor by interacting with the
      corticotrophin-releasing hormone-driven endocrine axis.

PMID- 18833325
TI  - Distractor inhibition predicts individual differences in the attentional blink.
AB  - BACKGROUND: The attentional blink (AB) refers to humans' impaired ability to
      detect the second of two targets (T2) in a rapid serial visual presentation
      (RSVP) stream of distractors if it appears within 200-600 ms of the first target
      (T1). Here we examined whether humans' ability to inhibit distractors in the RSVP
      stream is a key determinant of individual differences in T1 performance and AB
      magnitude. METHODOLOGY/PRINCIPAL FINDINGS: We presented subjects with RSVP
      streams (93.3 ms/item) of letters containing white distractors, a red T1 and a
      green T2. Subjects' ability to suppress distractors was assessed by determining
      the extent to which their second target performance was primed by a preceding
      distractor that shared the same identity as T2. Individual subjects' magnitude of
      T2 priming from this distractor was found to be negatively correlated with their
      T1 accuracy and positively related to their AB magnitude. In particular, subjects
      with attenuated ABs showed negative priming (i.e., worse T2 performance when the
      priming distractor appeared in the RSVP stream compared to when it was absent),
      whereas those with large ABs displayed positive priming (i.e., better T2
      performance when the priming distractor appeared in the RSVP stream compared to
      when it was absent). Thus, a subject's ability to suppress distractors, as
      assessed by T2 priming magnitude, predicted both their T1 performance and AB
      magnitude. CONCLUSIONS/SIGNIFICANCE: These results confirm that distractor
      suppression plays a key role in RSVP target selection and support the hypothesis
      that the AB results, at least in part, from a failure of distractor inhibition.

PMID- 18833326
TI  - MUC1* mediates the growth of human pluripotent stem cells.
AB  - The MUC1 protein is aberrantly expressed on an estimated 75% of all human solid
      tumor cancers. We recently reported that a transmembrane cleavage product, MUC1*,
      is the predominant form of the protein on cancer cells [1]. Further, our evidence
      indicated that MUC1* functions as a growth factor receptor on tumor cells, while
      the full-length protein appeared to have no growth promoting activity. Here, we
      report that MUC1* acts as a growth factor receptor on undifferentiated human
      embryonic stem cells (hESCs). Cleavage of the full-length ectodomain to form
      MUC1*, a membrane receptor, appears to make binding to its ligand, NM23,
      possible. Unexpectedly, we found that newly differentiated cells no longer
      express the cleaved form, MUC1*, or its ligand, NM23. Newly differentiated stem
      cells exclusively present full-length MUC1. Antibody-induced dimerization of the
      MUC1* receptor on hESCs stimulated cell growth to a far greater degree than
      currently used methods that require the addition of exogenous basic fibroblast
      growth factor (bFGF) as well as factors secreted by fibroblast "feeder cells".
      Further, MUC1* mediated growth was shown to be independent of growth stimulated
      by bFGF or the milieu of factors secreted by feeder cells. Stimulating the MUC1*
      receptor with either the cognate antibody or its ligand NM23 enabled hESC growth
      in a feeder cell-free system and produced pluripotent colonies that resisted
      spontaneous differentiation. These findings suggest that this primal growth
      mechanism could be utilized to propagate large numbers of pluripotent stem cells
      for therapeutic interventions.

PMID- 18833327
TI  - The cell signaling adaptor protein EPS-8 is essential for C. elegans epidermal
      elongation and interacts with the ankyrin repeat protein VAB-19.
AB  - BACKGROUND: The epidermal cells of the C. elegans embryo undergo coordinated cell
      shape changes that result in the morphogenetic process of elongation. The
      cytoskeletal ankyrin repeat protein VAB-19 is required for cell shape changes and
      localizes to cell-matrix attachment structures. The molecular functions of VAB-19
      in this process are obscure, as no previous interactors for VAB-19 have been
      described. METHODOLOGY/PRINCIPAL FINDINGS: In screens for VAB-19 binding proteins
      we identified the signaling adaptor EPS-8. Within C. elegans epidermal cells, EPS
      8 and VAB-19 colocalize at cell-matrix attachment structures. The central domain
      of EPS-8 is necessary and sufficient for its interaction with VAB-19. eps-8 null
      mutants, like vab-19 mutants, are defective in epidermal elongation and in
      epidermal-muscle attachment. The eps-8 locus encodes two isoforms, EPS-8A and EPS
      8B, that appear to act redundantly in epidermal elongation. The function of EPS-8
      in epidermal development involves its N-terminal PTB and central domains, and is
      independent of its C-terminal SH3 and actin-binding domains. VAB-19 appears to
      act earlier in the biogenesis of attachment structures and may recruit EPS-8 to
      these structures. CONCLUSIONS/SIGNIFICANCE: EPS-8 and VAB-19 define a novel
      pathway acting at cell-matrix attachments to regulate epithelial cell shape. This
      is the first report of a role for EPS-8 proteins in cell-matrix attachments. The
      existence of EPS-8B-like isoforms in Drosophila suggests this function of EPS-8
      proteins could be conserved among other organisms.

PMID- 18833328
TI  - The evolution of HoxD-11 expression in the bird wing: insights from Alligator
      mississippiensis.
AB  - BACKGROUND: Comparative morphology identifies the digits of the wing of birds as
      1,2 and 3, but they develop at embryological positions that become digits 2, 3
      and 4 in other amniotes. A hypothesis to explain this is that a homeotic frame
      shift of digital identity occurred in the evolution of the bird wing, such that
      digits 1,2 and 3 are developing from embryological positions 2, 3 and 4. Digit 1
      of the mouse is the only digit that shows no late expression of HoxD-11. This is
      also true for the anterior digit of the bird wing, suggesting this digit is
      actually a digit 1. If this is the case, we can expect closer relatives of birds
      to show no HoxD-11 expression only in digit 1. To test this prediction we
      investigate HoxD-11 expression in crocodilians, the closest living relatives of
      birds. METHODOLOGY/PRINCIPAL FINDINGS: Using degenerate primers we cloned a 606
      nucleotide fragment of exon 1 of the alligator HoxD-11 gene and used it for whole
      mount in-situ detection in alligator embryos. We found that in the pentadactyl
      forelimbs of alligator, as in the mouse, late expression of HoxD-11 is absent
      only in digit 1. CONCLUSIONS/SIGNIFICANCE: The ancestral condition for amniotes
      is that late-phase HoxD-11 expression is absent only in digit 1. The biphalangeal
      morphology and lack of HoxD-11 expression of the anterior digit of the wing is
      like digit 1 of alligator and mouse, but its embryological position as digit 2 is
      derived. HoxD-11 expression in alligator is consistent with the hypothesis that
      both digit morphology as well as HoxD-11 expression are shifted towards posterior
      in the bird wing.

PMID- 18833329
TI  - Reference ranges for the clinical laboratory derived from a rural population in
      Kericho, Kenya.
AB  - The conduct of Phase I/II HIV vaccine trials internationally necessitates the
      development of region-specific clinical reference ranges for trial enrollment and
      participant monitoring. A population based cohort of adults in Kericho, Kenya, a
      potential vaccine trial site, allowed development of clinical laboratory
      reference ranges. Lymphocyte immunophenotyping was performed on 1293 HIV
      seronegative study participants. Hematology and clinical chemistry were performed
      on up to 1541 cohort enrollees. The ratio of males to females was 1.9:1. Means,
      medians and 95% reference ranges were calculated and compared with those from
      other nations. The median CD4+ T cell count for the group was 810 cells/microl.
      There were significant gender differences for both red and white blood cell
      parameters. Kenyan subjects had lower median hemoglobin concentrations (9.5 g/dL;
      range 6.7-11.1) and neutrophil counts (1850 cells/microl; range 914-4715)
      compared to North Americans. Kenyan clinical chemistry reference ranges were
      comparable to those from the USA, with the exception of the upper limits for
      bilirubin and blood urea nitrogen, which were 2.3-fold higher and 1.5-fold lower,
      respectively. This study is the first to assess clinical reference ranges for a
      highland community in Kenya and highlights the need to define clinical laboratory
      ranges from the national community not only for clinical research but also care
      and treatment.

PMID- 18833330
TI  - An intracellular antioxidant determines the expression of a melanin-based signal
      in a bird.
AB  - To understand how traits used in animal communication evolved and are maintained
      as honest signals, we need to understand the mechanisms that prevent cheating. It
      has been proposed that honest signaling is guaranteed by the costs associated
      with the signal expression. However, the nature of these costs is still under
      debate. Melanin-based signals are intriguing because their expression seems to be
      tightly controlled by genes and the resource involved (i.e. melanin) seems to be
      not limited. However, in vertebrates, low levels of a key intracellular
      antioxidant (i.e. glutathione) are needed to promote melanogenesis. We propose
      that melanin-based ornaments can signal the ability to cope with oxidative stress
      because those individuals with low enough levels of glutathione, such as those
      required for melanin production, should manage well the whole of the antioxidant
      machinery in order to maintain a certain oxidative status. We analysed the
      expression of a melanin-based signal: the well-known black stripe of the great
      tit (Parus major). Great tit nestlings were injected with a specific inhibitor of
      glutathione production (DL-buthionine-S,R-sulfoximine; BSO) throughout their
      development. BSO effectively decreased intracellular glutathione levels without
      apparent side effects on growth or body condition. Instead, treated nestlings
      developed black breast stripes 70-100% larger than controls. Moreover, treated
      nestlings also compensated the decrease in glutathione levels by increasing the
      levels of circulating antioxidants. Results indicate that melanin-based signals
      can be at least partially permeable to environmental influences such as those
      associated to oxidative stress. They also reveal a potential handicap associated
      to the expression of this kind of signals. Finally, although other contributing
      factors could have been present, our findings emphasize the role of oxidative
      stress in shaping the evolution of animal signals in general and, in particular,
      those produced by pigments.

PMID- 18833331
TI  - Polymicrobial nature of chronic diabetic foot ulcer biofilm infections determined
      using bacterial tag encoded FLX amplicon pyrosequencing (bTEFAP).
AB  - BACKGROUND: Diabetic extremity ulcers are associated with chronic infections.
      Such ulcer infections are too often followed by amputation because there is
      little or no understanding of the ecology of such infections or how to control or
      eliminate this type of chronic infection. A primary impediment to the healing of
      chronic wounds is biofilm phenotype infections. Diabetic foot ulcers are the most
      common, disabling, and costly complications of diabetes. Here we seek to derive a
      better understanding of the polymicrobial nature of chronic diabetic extremity
      ulcer infections. METHODS AND FINDINGS: Using a new bacterial tag encoded FLX
      amplicon pyrosequencing (bTEFAP) approach we have evaluated the bacterial
      diversity of 40 chronic diabetic foot ulcers from different patients. The most
      prevalent bacterial genus associated with diabetic chronic wounds was
      Corynebacterium spp. Findings also show that obligate anaerobes including
      Bacteroides, Peptoniphilus, Fingoldia, Anaerococcus, and Peptostreptococcus spp.
      are ubiquitous in diabetic ulcers, comprising a significant portion of the wound
      biofilm communities. Other major components of the bacterial communities included
      commonly cultured genera such as Streptococcus, Serratia, Staphylococcus and
      Enterococcus spp. CONCLUSIONS: In this article, we highlight the patterns of
      population diversity observed in the samples and introduce preliminary evidence
      to support the concept of functional equivalent pathogroups (FEP). Here we
      introduce FEP as consortia of genotypically distinct bacteria that symbiotically
      produce a pathogenic community. According to this hypothesis, individual members
      of these communities when they occur alone may not cause disease but when they
      coaggregate or consort together into a FEP the synergistic effect provides the
      functional equivalence of well-known pathogens, such as Staphylococcus aureus,
      giving the biofilm community the factors necessary to maintain chronic biofilm
      infections. Further work is definitely warranted and needed in order to prove
      whether the FEPs concept is a viable hypothesis. The findings here also suggest
      that traditional culturing methods may be extremely biased as a diagnostic tool
      as they select for easily cultured organisms such as Staphylococcus aureus and
      against difficult to culture bacteria such as anaerobes. While PCR methods also
      have bias, further work is now needed in comparing traditional culture results to
      high-resolution molecular diagnostic methods such as bTEFAP.

PMID- 18833332
TI  - Common and unique contributions of decorin-binding proteins A and B to the
      overall virulence of Borrelia burgdorferi.
AB  - As an extracellular bacterium, the Lyme disease spirochete Borrelia burgdorferi
      resides primarily in the extracellular matrix and connective tissues and between
      host cells during mammalian infection, where decorin and glycosaminoglycans are
      abundantly found, so its interactions with these host ligands potentially affect
      various aspects of infection. Decorin-binding proteins (Dbps) A and B, encoded by
      a 2-gene operon, are outer surface lipoproteins with similar molecular weights
      and share approximately 40% identity, and both bind decorin and
      glycosaminoglycans. To investigate how DbpA and DbpB contribute differently to
      the overall virulence of B. burgdorferi, a dbpAB mutant was modified to
      overproduce the adhesins. Overproduction of either DbpA or DbpB resulted in
      restoration of the infectivity of the mutant to the control level, measured by
      50% infectious dose (ID(50)), indicating that the two virulence factors are
      interchangeable in this regard. Overproduction of DbpA also allowed the mutant to
      disseminate to some but not all distal tissues slightly slower than the control,
      but the mutant with DbpB overproduction showed severely impaired dissemination to
      all tissues that were analyzed. The mutant with DbpA overproduction colonized all
      tissues, albeit generating bacterial loads significantly lower than the control
      in heart and joint, while the mutant overproducing DbpB remained severely
      defective in heart colonization and registered bacterial loads substantially
      lower than the control in joint. Taken together, the study indicated that DbpA
      and DbpB play a similar role in contribution to infectivity as measured by ID(50)
      value but contribute differently to dissemination and tissue colonization.

PMID- 18833333
TI  - How to use the world's scarce selenium resources efficiently to increase the
      selenium concentration in food.
AB  - The world's rare selenium resources need to be managed carefully. Selenium is
      extracted as a by-product of copper mining and there are no deposits that can be
      mined for selenium alone. Selenium has unique properties as a semi-conductor,
      making it of special value to industry, but it is also an essential nutrient for
      humans and animals and may promote plant growth and quality. Selenium deficiency
      is regarded as a major health problem for 0.5 to 1 billion people worldwide,
      while an even larger number may consume less selenium than required for optimal
      protection against cancer, cardiovascular diseases and severe infectious diseases
      including HIV disease. Efficient recycling of selenium is difficult. Selenium is
      added in some commercial fertilizers, but only a small proportion is taken up by
      plants and much of the remainder is lost for future utilization. Large
      biofortification programmes with selenium added to commercial fertilizers may
      therefore be a fortification method that is too wasteful to be applied to large
      areas of our planet. Direct addition of selenium compounds to food (process
      fortification) can be undertaken by the food industry. If selenomethionine is
      added directly to food, however, oxidation due to heat processing needs to be
      avoided. New ways to biofortify food products are needed, and it is generally
      observed that there is less wastage if selenium is added late in the production
      chain rather than early. On these bases we have proposed adding selenium
      enriched, sprouted cereal grain during food processing as an efficient way to
      introduce this nutrient into deficient diets. Selenium is a non-renewable
      resource. There is now an enormous wastage of selenium associated with large
      scale mining and industrial processing. We recommend that this must be changed
      and that much of the selenium that is extracted should be stockpiled for use as a
      nutrient by future generations.

PMID- 18833334
TI  - Isolation of autochthonous non-white rot fungi with potential for enzymatic
      upgrading of Venezuelan extra-heavy crude oil.
AB  - The increasing world demand for fuels makes it necessary to exploit the largest
      reserve of extra-heavy crude oil (EHCO) of the Orinoco Oil Belt from Venezuela.
      We propose the use of extracellular oxidative enzymes, in particular, lignin
      degrading enzyme systems (LDS) of fungi, for enzymatic improvement of EHCO.
      Autochthonous non-white rot fungal strains able to use EHCO, and several
      polycyclic aromatic hydrocarbons (PAHs) as sole carbon source and energy, were
      isolated from EHCO-polluted soils and identified as belonging to the genera
      Fusarium, Penicillium , Trichoderma , Aspergillus , Neosartorya,
      Pseudallescheria, Cladosporium, Pestalotiopsis , Phoma and Paecillomyces.
      Phenotypic and biochemical assays revealed the ability of these filamentous fungi
      to synthesize extracellular oxidative enzymes, and suggested a relationship
      between the LDS and EHCO bioconversion. This work reports, for the first time,
      the use of o-phenylenediamine dihydrochloride (OPD) as substrate to measure
      extracellular ligninolytic peroxidases (ELP) in culture broths of filamentous
      fungi (Fusarium solani HP-1), and constitutes the first formal study of the
      fungal community associated with the EHCO of the Orinoco Oil Belt.

PMID- 18833335
TI  - Superior effect of forceful compared with standard traction mobilizations in hip
      disability?
AB  - THE OBJECTIVE OF THIS STUDY WAS TO COMPARE THE EFFECTIVENESS OF TWO COMPILED
      PHYSIOTHERAPY PROGRAMS: one including forceful traction mobilizations, the other
      including traction with unknown force, in patients with hip disability according
      to ICF (the International Classification of Functioning, Disability and Health,
      2001; WHO), using a block randomized, controlled trial with two parallel
      treatment groups in a regular private outpatient physiotherapy practice. In the
      experimental group (E; n = 10) and control group (C; n = 9), the mean (+/-SD) age
      for all participants was 59 +/- 12 years. They were recruited from outpatient
      physiotherapy clinics, had persistent pain located at the hip joint for >8 weeks
      and hip hypomobility. Both groups received exercise, information and manual
      traction mobilization. In E, the traction force was progressed to 800 N, whereas
      in C it was unknown. Major outcome measure was the median total change score
      >/=20 points or >/=50% of the disease- and joint-specific Hip disability and
      Osteoarthritis Outcome Score (HOOS), compiled of Pain, Stiffness, Function and
      Hip-related quality of life (ranging 0-100). The mean (range) treatments received
      were 13 (7-16) over 5-12 weeks and 20 (18-24) over 12 weeks for E and C,
      respectively. The experimental group showed superior clinical post-treatment
      effect on HOOS (>/=20 points), in six of 10 participants compared with none of
      nine in the control group (p = 0.011). The effect size was 1.1. The results
      suggest that a compiled physiotherapy program including forceful traction
      mobilizations are short-term effective in reducing self-rated hip disability in
      primary healthcare. The long-term effect is to be documented.

PMID- 18833336
TI  - Meiotic regulation of TPX2 protein levels governs cell cycle progression in mouse
      oocytes.
AB  - Formation of female gametes requires acentriolar spindle assembly during meiosis.
      Mitotic spindles organize from centrosomes and via local activation of the
      RanGTPase on chromosomes. Vertebrate oocytes present a RanGTP gradient centred on
      chromatin at all stages of meiotic maturation. However, this gradient is
      dispensable for assembly of the first meiotic spindle. To understand this meiosis
      I peculiarity, we studied TPX2, a Ran target, in mouse oocytes. Strikingly, TPX2
      activity is controlled at the protein level through its accumulation from meiosis
      I to II. By RNAi depletion and live imaging, we show that TPX2 is required for
      spindle assembly via two distinct functions. It controls microtubule assembly and
      spindle pole integrity via the phosphorylation of TACC3, a regulator of MTOCs
      activity. We show that meiotic spindle formation in vivo depends on the
      regulation of at least a target of Ran, TPX2, rather than on the regulation of
      the RanGTP gradient itself.

PMID- 18833337
TI  - Synthesis and Conformations of Dendronized Poly(L-lysine).
AB  - Dendronized polymers based on a poly(L-lysine) backbone have been synthesized up
      to the fourth generation. The hydroxyl-terminated polymers are completely water
      soluble, which makes them good candidates for drug delivery applications. The
      dendronized polypeptide backbones are helical at lower generations, but undergo a
      dramatic conformational change from alpha-helical to disordered upon increasing
      the dendron size to the third generation. This conformational change, attributed
      to steric repulsions between dendrons, is supported by spectroscopic measurements
      while chain extension upon dendronization is confirmed by scanning force
      microscopy.

PMID- 18833341
TI  - Mitochondrial DNA evidence for a diversified origin of workers building First
      Emperor of China.
AB  - Variant studies on ancient DNA have attempted to reveal individual origin. Here,
      based on cloning sequencing and polymerase chain reaction-restriction fragment
      length polymorphisms, we analyzed polymorphisms in the first hypervariable region
      and coding regions of mitochondrial DNA of 19 human bone remains which were
      excavated from a tomb near the Terra Cotta Warriors and dated some 2,200 years
      before present. With the aim of shedding light on origins of these samples who
      were supposed to be workers building the mausoleum for the First Emperor of
      China, we compared them with 2,164 mtDNA profiles from 32 contemporary Chinese
      populations at both population and individual levels. Our results showed that
      mausoleum-building workers may be derived from very diverse sources of origin.

PMID- 18833342
TI  - Gliomatosis cerebri with favorable outcome in a child: a case report.
AB  - OBJECTIVE: To report a rare clinical case of gliomatosis cerebri with favorable
      outcome in a 3-year old child. DESCRIPTION: A 3-year old child developed severe
      and progressive symptoms of gliomatosis cerebri. The initial tests were
      unspecific. After clinical improvement following neuroendoscopic surgery, there
      was a progressive decline in clinical status with development of obstructive
      hydrocephalus, paraparesis and difficulty in walking. The child was again
      submitted to surgery after disseminated injuries in the subarachnoid space were
      identified. She also received chemotherapy and radiotherapy. Currently, 6 years
      later, spinal canal and brain injuries remain unaltered, with marked
      syringomyelia. However, the child is clinically stable, with adequate development
      for her age, indicating a satisfactory response to treatment. COMMENTS: The
      child's clinical presentation and the combination of symptoms led to the
      diagnosis of gliomatosis cerebri. There are few descriptions of this kind of
      tumor in children in the literature, and none reports a favorable outcome as in
      the present case.

PMID- 18833343
TI  - Toilet training: situation at 2 years of age in a birth cohort.
AB  - OBJECTIVES: Acquisition of bladder and bowel control is influenced by
      physiological, psychological and sociocultural factors. The objective of this
      study was to evaluate the prevalence of children out of diapers by 24 months of
      age and the factors associated with this finding. METHODS: A total of 3,281
      children born in Pelotas, RS, Brazil in 2004 were enrolled on a longitudinal
      study. At 24 months their mothers were visited at home and replied to a
      questionnaire containing questions about sociodemographic data and the
      characteristics of their children's urinary and intestinal evacuation habits,
      with special attention to toilet training. Multivariate analyses were carried out
      using Poisson regression. RESULTS: From the total, 24.3% were out of diapers
      during the day, with the female sex predominating (27.8 vs. 21.1%, p < 0.001) and
      8.6% were out of diapers at night, also with the female sex predominating (10.6
      vs. 6.8%, p < 0.001). The abilities needed to start toilet training were present
      in 85.5% of the children. Guidance was received from a pediatrician in 10% of
      cases, and more frequently among richer mothers than among poorer mothers (22.9
      vs. 4.8%). Mothers who spent more years in education (13.2%) and were from higher
      social classes (14%) took their children out of diapers later; a greater number
      of children living at home (relative risk = 1.32) and being able to communicate
      the need to go to the toilet (relative risk = 11.74) both increased the
      probability of being out of diapers; previous unsuccessful attempts delayed
      removal of diapers (relative risk = 0.59). CONCLUSIONS: Although the abilities
      needed for acquisition of bladder and bowel control were already present at 24
      months, indicating that toilet training could be started, the majority of
      children had not yet started this training. Better-informed mothers delayed
      training the most.

PMID- 18833345
TI  - Beyond method: constructing "anthropoepidemiological" methods.

PMID- 18833344
TI  - Anthropology and Epidemiology: learning epistemological lessons through a
      collaborative venture.
AB  - Collaboration between anthropology and epidemiology has a long and tumultuous
      history. Based on empirical examples, this paper describes a number of
      epistemological lessons we have learned through our experience of cross
      disciplinary collaboration. Although critical of both mainstream epidemiology and
      medical anthropology, our analysis focuses on the implications of addressing each
      discipline's main epistemological differences, while addressing the goal of
      adopting a broader social approach to health improvement. We believe it is
      important to push the boundaries of research collaborations from the more
      standard forms of "multidisciplinarity," to the adoption of theoretically imbued
      "interdisciplinarity." The more we challenge epistemological limitations and
      modify ways of knowing, the more we will be able to provide in-depth explanations
      for the emergence of disease-patterns and thus, to problem-solve. In our
      experience, both institutional support and the adoption of a relativistic
      attitude are necessary conditions for sustained theoretical interdisciplinarity.
      Until researchers acknowledge that methodology is merely a human-designed tool to
      interpret reality, unnecessary methodological hyper-specialization will continue
      to alienate one field of knowledge from the other.

PMID- 18833346
TI  - Is epidemiology beginning to dialogue with anthropology?

PMID- 18833347
TI  - 'Undisciplinary' comments from evaluative research in health.

PMID- 18833349
TI  - "Get back to where you once belonged": monitoring the AIDS pandemic in the 21st
      century.
AB  - This paper reviews the concepts and methodological strategies that have shaped
      the monitoring of the AIDS pandemic, today in its third decade. A deliberate
      effort was made to highlight aspects usually forgotten by the canon. The paper
      aims to track the footsteps of the evolving strategies in the field of
      surveillance & monitoring, with the help of disciplines such as epidemiology,
      molecular biology, social, and behavioral sciences. The deep divide that opposes
      societies severely affected by the epidemic and affluent societies much less
      affected by the epidemic is contrasted with the scarce human and financial
      resources of the societies facing harshest epidemic vis-a-vis the
      comprehensiveness of the response to the epidemic in their affluent counterparts
      in terms of the scope and high standards of their initiatives on monitoring,
      prevention, management & care. The pressing need to implement feasible
      alternatives to the current sophisticated and expensive ones is briefly
      discussed. Beyond the renewed challenge posed to the creativity of scientists and
      health professionals, the AIDS pandemic is described as a major public health
      crisis, compromising the social fabric in some contexts, and as a never fulfilled
      calling for an ethics of solidarity between different societies and different
      social strata of each given society.

PMID- 18833350
TI  - Transdisciplinary research strategies for understanding socially patterned
      disease: the Asthma Coalition on Community, Environment, and Social Stress
      (ACCESS) project as a case study.
AB  - As we have seen a global increase in asthma in the past three decades it has also
      become clear that it is a socially patterned disease, based on demographic and
      socioeconomic indicators clustered by areas of residence. This trend is not
      readily explained by traditional genetic paradigms or physical environmental
      exposures when considered alone. This has led to consideration of the interplay
      among physical and psychosocial environmental hazards and the molecular and
      genetic determinants of risk (i.e., biomedical framing) within the broader
      socioenvironmental context including socioeconomic position as an upstream "cause
      of the causes" (i.e., ecological framing). Transdisciplinary research strategies
      or programs that embrace this complexity through a shared conceptual framework
      that integrates diverse discipline-specific theories, models, measures, and
      analytical methods into ongoing asthma research may contribute most significantly
      toward furthering our understanding of socially patterned disease. This paper
      provides an overview of a multilevel, multimethod longitudinal study, the Asthma
      Coalition on Community, Environment and Social Stress (ACCESS), as a case study
      to exemplify both the opportunities and challenges of transdisciplinary research
      on urban asthma expression in the United States.

PMID- 18833351
TI  - The many faces of epidemiology: evolutionary epidemiology.
AB  - We review important issues revealed by the application of the evolutionary theory
      to epidemiological problems. The scope is restricted to infectious diseases and
      the evolution of virulence as a consequence of public health strategies to
      control transmission. We focus on the discussion about the possibility of
      virulence management and explore current scenarios in which recent advances in
      molecular biology and genetics offer new tools to monitor and change diversity
      among pathogens, vertebrate and invertebrate hosts. We stress the need to
      integrate the analytical framework of epidemiology into population genetics and
      evolutionary theory. We anticipate as an outcome of this process the development
      of study designs and analytical tools to predict the evolutionary implications of
      control measures in the population and surveillance mechanisms to continuously
      monitor the changes in pathogen virulence patterns. Communication among modelers,
      epidemiologists and molecular biologists is essential in order to design model
      driven field trials and to develop data-driven analytical tools leading to
      conclusive findings that can inform the public health oriented decision making
      process.

PMID- 18833352
TI  - Georeferenced data in epidemiologic research.
AB  - This paper reviews some conceptual and practical issues regarding the application
      of georeferenced data in epidemiologic research. Starting with the disease
      mapping tradition of geographical medicine, topics such as types of georeferenced
      data, implications for data analysis, spatial autocorrelation and main analytical
      approaches are heuristically discussed, relying on examples from the
      epidemiologic literature, most of them concerning mapping disease distribution,
      detection of disease spatial clustering, evaluation of exposure in environmental
      health investigation and ecological correlation studies. As for concluding
      remarks, special topics that deserve further development, including the misuses
      of the concept of space in epidemiologic research, issues related to data quality
      and confidentiality, the role of epidemiologic designs for spatial research,
      sensitivity analysis and spatiotemporal modeling, are presented.

PMID- 18833353
TI  - [Networks: epidemiology of transmissible diseases from a systemic perspective].
AB  - The direct or indirect physical contact between human beings as a basic condition
      for the transmission of infectious diseases stimulated epidemiologists to put
      forth great efforts to understanding and describing the process of human
      contacts. It is through these contacts that disease spreads over populations and
      emerges, at the systemic level, in the form of epidemics. During the 20th
      century, many researchers dedicated themselves to revealing the population
      patterns that favor or not the emergence of epidemics and their temporal and
      spatial dynamics. The first insights came from population models adapted from the
      physical sciences, in which non-structured populations are considered. Later on
      it became clear that a more detailed description of social structures was
      required to correctly describe epidemic dynamics, and concepts such as social
      group, social network and social cohesion became important terms in the
      quantitative study of epidemics. The approximation between epidemiology and the
      social sciences turns obvious as their concepts are interacting more and more. To
      give a brief overview of this trajectory is the purpose of this article.

PMID- 18833354
TI  - [Energy expenditure of adults in the city of Niteroi, state of Rio de Janeiro:
      nutrition, Physical activity and Health Survey--PNAFS].
AB  - The accurate assessment of energy expenditure (EE) and of the physical activity
      level (PAL) is important for establishing the energy requirements (ER) of
      populations. Little is known about these variables in the Brazilian population.
      The purpose of the present study was to assess EE and PAL in the adult population
      (> 20 years) of Niteroi, RJ. An adapted version of the MOSPA time-budget
      questionnaire was used to assess the duration of the daily activities of the
      subjects. The energy cost of the activities was obtained from the table published
      by FAO in 2004, expressed as multiples of the basal metabolic rate (BMR) measured
      by indirect calorimetry. Total daily EE (TDEE) was calculated as the sum of EE of
      all activities of a typical daily routine. TDEE was higher in males than in
      females (2382.0 + 38.0 and 1987.1 + 22.9 kcal.day-1 respectively) but women
      showed higher PAL values (1.70 + 0.02 and 1.75 + 0.01 respectively). ER estimated
      using a PAL of 1.40 was the best predictor of EE of the population in all
      nutritional status categories, particularly for males. In conclusion, it seems
      prudent to use lower PAL values when estimating the ER of the adult population of
      Niteroi. It is also evident that more data on the energy cost of activities must
      be generated for establishing the ER of the Brazilian population.

PMID- 18833355
TI  - [Urban health: "the city is a strange lady, smiling today, devouring you
      tomorrow"].
AB  - More than half of the world's population is living in cities and the world is
      turning more and more urbanized. This literature review explores the
      ramifications of urban transformation, showing how cities take shape and impact
      human health in our times. While cities can offer positive opportunities, their
      negative impacts related to the lack of social organization, precarious urban
      living and working conditions, lack of governance and opportunities as well as
      the lack of strategies for promoting social equity tend to increase the adverse
      effects on the health of the urban communities. The article also advocates the
      study of urban health as a branch of knowledge related to public health,
      proposing a common conceptual model and taxonomy for urban health. Future
      directions for research and practice are discussed in the light of some examples
      from the Brazilian scientific literature.

PMID- 18833356
TI  - [The impact of oral health on the quality of life of HIV infected children: a
      literature review].
AB  - The search for improvement of the health of systemically compromised patients and
      for a better knowledge about the impact of diseases on their lives has brought
      great interest for health-related quality of life, mainly in children with
      chronic diseases. The quality of life related to oral health is thus relevant,
      not only for being an inseparable component of the general health but also due to
      the importance of oral problems in the lives of these patients. The evaluation of
      oral health-related quality of life in HIV infected children can be of great
      importance seen that these patients show high prevalence of caries and
      periodontal diseases besides the oral manifestations of the virus infection
      itself. The aim of this article is to present some concepts about quality of life
      and the use of instruments for its evaluation on the basis of a literature review
      as well as to analyze the impact of oral health on the quality of life of HIV
      infected children.

PMID- 18833357
TI  - [From condom use to prevention of STD/AIDS].
AB  - Men s attitudes were investigated regarding the condom use in heterosexual
      intercourse. The study was characterized as secondary analysis of part of wider
      research aiming to understand power in heterosexual intercourse from the man s
      perspective. The secondary analysis proposed to analyze research data obtained
      and analyzed in a previous study to answer questions other than those contained
      in the original study. Ten men from west Santa Catarina took part in the original
      study; for the present study the data of participant identification, the group
      discussion and the interview of the original study were used. The data analysis
      comprised reading all the information, extracting common reports, grouping codes
      according to their nature; category formation. The results showed men s attitudes
      in the following categories: condom only to prevent pregnancy; condom with the
      wife denotes cheating; the condom should be used when 'out'; I have never used a
      condom; safe sex. In STD/AIDS prevention, aspects linked to beliefs, myths,
      health stereotypes and the characteristics of man-woman relationships become
      entwined.

PMID- 18833358
TI  - Evaluation of STD/HIV/AIDS peer-education and danger: a local perspective.
AB  - An evaluation of peer-education projects with sex workers, men who have sex with
      men and marginalized adolescents, was introduced in a remote region of Brazil.
      The context of varied limits of predictability made it difficult to conduct
      inquiry. To go beyond available epidemiological surveys and questionnaires on
      sexual behavior, a self-evaluation aimed at increasing pragmatic knowledge about
      prevention in a challenging socio-political context. During five-months, a
      participatory-action research explored participant observation; individual and
      collective exchanges with users, peer-educators, coordinators, administrators,
      politicians and regional health professionals. Collective understanding of peer
      education in prostitution zones underlines the reality of unforeseen social
      repercussions and confluence/divergence of multiple actors' perspectives. It
      identifies meaningful dimensions at a community-level, such as the collective
      history and dangerous working conditions. Nurses face complex struggles and
      negotiations over multiple actors in their practice. This study suggests that
      nurses have a role to play in the conceptualization of participatory evaluation.
      It also underlines the threats to their physical and social safety, which they
      might share with peer-educators.

PMID- 18833359
TI  - [Evaluating the existence of oral infection control in patients admitted in state
      hospitals in Rio de Janeiro].
AB  - The aim of the present study is to ascertain whether an oral infection control
      protocol is being used in Rio de Janeiro State hospitals. Sixty two hospitals,
      both public and private have been surveyed. When asked whether any procedure was
      being adopted with admitted patients (in case of ICU patients), 39% of the
      hospitals responded positively. Among all institutions surveyed, only 15% conduct
      a regular plaque control protocol in admitted patients. Studies have shown that
      there is an inter-relationship between periodontal disease and systemic diseases,
      such as cardiovascular disease, osteoporosis, preterm births and low birthweight,
      diabetes and respiratory diseases. The oral cavity is considered a potent
      reservoir of respiratory pathogens. Based on these findings, it has become
      evident that oral hygiene is an important means of preventing a number of
      diseases. Thus the need arises not only to create an oral cavity infection
      control protocol that will contribute to reduce mortality in admitted patients
      but also to propose preventive measures towards this end.

PMID- 18833360
TI  - [The knowledge of the aged about HIV/AIDS: epidemiologic study in Vale do Rio dos
      Sinos, Rio Grande do Sul, Brazil].
AB  - The objective of this study was to assess the knowledge about HIV/AIDS in
      participants of companionship groups in the Vale do Sinos, Rio Grande do Sul,
      Brazil. It was a prospective cross-sectional study in a sample of 510
      individuals, 17% males and 82.5% females aged between 60 and 90 years. We used
      the Questionnaire on HIV for the Old Aged, which comprises the general
      characteristics of the participants and questions concerning HIV/AIDS, organized
      into the elements 'concept', 'transmission', 'prevention', 'vulnerability', and
      'treatment'. Nearly half of the participants (48.4 %) reported having studied 4
      to 7 years and the monthly income of 52.2% was of 1 to 3 minimum wages. In the
      dimensions concept and transmission, 49.4% had no idea about the asymptomatic
      phase of the infection, and 41.4% believed HIV could be transmitted by a mosquito
      bite. With regard to prevention and vulnerability, 25.5% did not know about the
      female condom and 36.9% considered AIDS a disease confined to men who have sex
      with men, sex workers, and injection-drug users. Regarding antiretroviral
      treatment, 12.2% ignored its existence. Elderly people in companionship groups
      have important misconceptions about HIV/AIDS, which can increase their risk of
      infection. There is a need for public health programs directed to this population
      in order to prevent or decrease the risk of HIV transmission.

PMID- 18833361
TI  - [From "acute AIDS" to "chronic AIDS": body perception and surgical interventions
      in people living with HIV and AIDS].
AB  - The Brazilian government has been providing free and universal access to the
      HAART therapy for people living with HIV and AIDS for ten years. Since then, many
      epidemiological characteristics have changed, and AIDS passed scientifically and
      medically to be classified as a chronic condition. This qualitative study aims to
      comprehend the challenges posed by self-perception of body changes experienced by
      people living with AIDS during recent years, as a result of prolonged use of
      antiretroviral medication.With this purpose, in 1999 and 2005, 32 semi-structured
      interviews with HIV positive individuals were held in the State of Sao Paulo to
      capture the challenges occurred during this period, in particular with regard to
      the lipodystrophy syndrome. The analysis of the data indicates that even with the
      availability and use of new technologies that allowed for AIDS to transform into
      a chronic, clinically treatable disease, there are still important aspects lived
      by patients that reedit fears and difficulties similar to those of the initial
      periods of the epidemic, among others appearance-impairing physical stigma.

PMID- 18833362
TI  - [Adherence to an oral health program for HIV infected children and adolescents
      and the attitudes of their caretakers].
AB  - This study aimed to evaluate the adherence to an Oral Health Program (OHP) for
      HIV infected children and adolescents, as well as the attitudes of their
      caretakers regarding oral care. A total of 58 caretakers that accompany the
      children in medical appointments at an AIDS ambulatory were interviewed for
      collecting personal data and data regarding adherence to the OHP or other
      odontological treatment and attitudes related to oral care. Approximately 70% of
      the caretakers stated that their children participated in the OHAP, however 20%
      of them did not return to the recall appointments; such visits were even less
      frequent when the caretakers were not the parents themselves (p= 0.036). The
      adherence of this population to dental treatment outside the OHP was small, 48%
      of the caretakers stated that the child did not conclude the treatment when
      referred to another place for treatment. The attitude of the caretakers regarding
      dental care of HIV+ children was not considered satisfactory. Furthermore, it is
      very important to have pediatric dentists in the multi-professional teams that
      attend HIV+ children and adolescents and to promote this program among the
      parents and all medical teams involved with such patients.

PMID- 18833363
TI  - [Analyzing the risk problem in couples with serodiscordance].
AB  - This article relates an investigation made with people who live in a situation of
      partner serodiscordance, shall say in partnerships in which one partner is HIV
      positive and the other is HIV negative. The study is aimed at understanding how
      these people deal with the constant risk this situation involves. Fifteen
      individuals living with serodiscordant partners were interviewed in the Testing
      and Counseling Center of the Sao Francisco de Assis School Hospital of the
      Federal University of Rio de Janeiro. The fear of transmitting the HIV to the
      seronegative partner is constant. Besides the fear, there are the difficulties to
      talk about the problem, to plan the future and to keep a satisfactory sexual
      life. Condom use does not seem to be an easily adopted practice. The interviewees
      point to other factors that need to be taken into consideration beyond safe
      sexual practices and knowledge of the forms of HIV transmission. Such factors
      seem to depend much more directly on the capacity of the partners to construct a
      new couple identity in face of a risk situation. The risk of infection always
      lies in another being. Paradoxically, in this case the risk of infection comes
      from someone so close that the continuation of the partnership itself depends on
      this other being.

PMID- 18833364
TI  - [Asymmetry in international relations, industrial property rights and anti-HIV
      medication].
AB  - This paper analyzes the asymmetry in the international relations as refers to the
      recognition of industrial property rights in the pharmaceutical industry. It
      focuses on the impact of such relations upon the access to ARV medication, an
      issue of worldwide interest due to its connection with the development of the
      nations. Clashing interests and the position taken by some countries in their
      patent laws point to a scenario less favorable for the access of peripheral
      countries to anti-HIV/AIDS medication. On the other hand, it seems that the
      success of the Brazilian STD/AIDS program in negotiating ARV prices will open new
      possibilities. The solution may be the internal strengthening of the National
      States and the active role played by the Agencies of the United Nations System in
      defense of the collective human interests.

PMID- 18833365
TI  - [The knowledge of the population of Vicosa, MG, about the ways of AIDS
      transmission].
AB  - AIDS is a major public health problem reaching all social strata. Knowing about
      the ways of transmission is a way of preventing the disease. For evaluating the
      level of knowledge of the population of the city of Vicosa about AIDS
      transmission, a questionnaire about the ways of transmission of the disease based
      on studies made in Europe was applied to 376 individuals. The questionnaire
      consisted of eleven multiple-choice questions about the ways of AIDS
      transmission, sex, age and educational level of the interviewees. The results
      showed that the ways of transmission emphasized in health campaigns are well
      assimilated, while the questions about everyday situations that offer no risk
      received a high number of incorrect answers. The differences were not significant
      when data were stratified by sex. The same data stratified by age or educational
      level showed significant differences for some questions; people aged over 55 and
      with a lower educational level had a significantly higher number of incorrect
      answers. It can be concluded that the population of Vicosa knows the main ways of
      AIDS transmission, but a part of the population does not know that some everyday
      situations do not pose risk of transmission. These data can be useful for the
      preparation of elucidative campaigns for reducing prejudice.

PMID- 18833366
TI  - [Historical aspects, maternity and HIV infection in women].
AB  - The aim of this article was to examine historical aspects related to the feminine
      and to being a mother for deepening the comprehension of motherhood in the
      context of HIV/Aids infection. We reviewed the traditional role of the woman in
      society, showing the historical division between the mother, deserving respect
      and consideration, and the prostitute, marginalized and not worth of respect. In
      this context, we discuss the sexually transmitted diseases and the social
      reactions toward these infections in women, especially as refers to motherhood in
      the context of HIV/Aids infection. The paper emphasizes the presence of socially
      constructed beliefs about women's behaviors as a factor hampering an effective
      prevention of STD/HIV/AIDS in women and the great need for reflecting about the
      strategies for prevention and care.

PMID- 18833367
TI  - [HIV-testing for pregnant women in a Family Health Unit in Fortaleza, Ceara].
AB  - Free access to prenatal care and HIV tests represent the first step in the
      prevention of vertical transmission and guarantees early prophylactic measures.
      This study aims at analyzing the coverage of HIV testing in pregnant women in a
      Basic Family Health Unit in the city of Fortaleza, Ceara. The theoretical
      methodological basis of the study was the grounded theory, which proposes
      generation of theory from data derived from the social reality. Data were
      collected through participant observation, open interviews with physicians,
      nurses and pregnant women and in focal groups with pregnant women and health
      agents. The women faced institutional barriers to prenatal care and HIV testing.
      Difficulties in making the appointments for prenatal care hampered early
      identification of pregnant women and delayed their assistance. With respect to
      HIV testing, the study found that the Basic Health Unit does not collect the
      biologic material; there are few laboratories performing this kind of exam and
      those who do are very far from the pregnant women's residences. This study
      concludes that even in the Family Health Unit, the access to prenatal care for
      pregnant women remains difficult, and that the prevention of vertical HIV
      transmission depends on political, institutional and structural changes.

PMID- 18833368
TI  - A systematic review and meta-analysis of interventions used to reduce exposure to
      house dust and their effect on the development and severity of asthma.
AB  - We assessed whether any household dust reduction intervention has the effect of
      increasing or decreasing the development or severity of atopic disease.
      Electronic searches on household intervention and atopic disease were conducted
      in 2007 in EMBASE, MEDLINE, and the Cochrane Central Register of Controlled
      Trials. We included randomized controlled trials comparing asthma outcomes in a
      household intervention group with either placebo intervention or no intervention.
      Meta-analyses on the prevention studies found that the interventions made no
      difference to the onset of wheeze but made a significant reduction in physician
      diagnosed asthma. Meta-analysis of lung function outcomes indicated no
      improvement due to the interventions but found a reduction in symptom days.
      Qualitatively, health care was used less in those receiving interventions.
      However, in one study that compared intervention, placebo, and control arms, the
      reduction in heath care use was similar in the placebo and intervention arms.
      This review suggests that there is not sufficient evidence to suggest
      implementing hygiene measures in an attempt to improve outcomes in existing
      atopic disease, but interventions from birth in those at high risk of atopy are
      useful in preventing diagnosed asthma but not parental-reported wheeze.

PMID- 18833369
TI  - [Anemia as a public health problem: the current situation].
AB  - In 1990, the United Nations held a World Summit in New York, in which goals for
      the upcoming decade were established. One of these goals was a one-third
      reduction in the prevalence of anemia among women at childbearing age. Despite
      this modest percentage, epidemiological indicators point to the opposite
      direction, indicating an increasing occurrence of anemia in different regions of
      the world, including in Brazil. These data show that anemia has continued since
      the antiquity to be one of the most prevalent and widespread diseases in human
      populations. Thus, a number of questions without answers arise regarding the
      actual prevalence and etiopathogenesis of the problem as well as with respect to
      the degree of implantation and the effectiveness of control measures.

PMID- 18833370
TI  - [Evaluation of the decentralization of epidemiologic surveillance to the Team of
      the Family Health Program].
AB  - The aim of this study is to evaluate the decentralization of Epidemiologic
      Surveillance actions to the Family Health Program in a city in the state of
      Bahia, Brazil. The research was conducted as a case study, using adapted
      techniques of thematic and evaluative analysis. In face of the need to adopt a
      model for this analysis, it was decided to adopt the political model of
      implantation analysis. The primary data were collected in semi-structured
      interviews with managers of the local Health Department and the Family Health
      Team and the secondary data through document analysis. The study demonstrated
      that Epidemiologic Surveillance is understood in three ways: as a kind of medical
      police action; as an instrument of surveillance focused on the control of
      transmissible diseases and as surveillance addressing the risk of damages. As
      refers to the capacity of intervention, although mainly directed to disease
      detection and control, the performance of the Family Health Team was found
      positive. We conclude that it is possible to decentralize Epidemiologic
      Surveillance to the Family Health Program but the effective implantation of this
      process will depend on the support of health managers and professionals and on a
      political project assuming the decentralization of epidemiologic survey a
      strategy towards reorganization of the healthcare system in the city.

PMID- 18833371
TI  - [Epidemiologic surveillance in the plan for intensification of malaria control
      actions in the state of Mato Grosso: a case study].
AB  - The objective of this study is to analyze the epidemiologic surveillance in the
      Malaria Control Actions Intensification Plan (PIACM) in the 18 cities of the
      state of Mato Grosso, from 1999 to 2002. An evaluative research of the type
      implantation analysis was conducted. The analysis was carried out using a logic
      model considering 4 dimensions - external and political context, organizational
      context, implementation and effectiveness - and 5 evidence bases, 3 of primary
      data and 2 of secondary data. The cities are called CASE. The data were collected
      using semi-structured questionnaires. The implementation of the PIACM actions was
      found adequate in only 5,6% of CASES. The effectiveness of the actions was
      adequate in only one CASE and none of the CASES showed adequate contextual
      characteristics. The principal factors affecting the implementation were:
      frequent changes of the local health managers and professionals, fragmented and
      sporadic training and health promotion and prevention actions limited to the
      primary care team. In conclusion, structural problems and lack of articulation of
      epidemiologic surveillance hamper the full development of the PIACM actions.

PMID- 18833372
TI  - [Model for evaluating plans for health service waste management (MPHSW) for use
      by local health and environmental protection authorities].
AB  - The inadequate management of the waste the health services are producing day by
      day and the considerable increase in quantity of this waste are increasingly
      posing hazards to the health of the population. Thus, the managers in charge of
      establishments that originate this waste should adopt a Management Plan for
      Health Service Waste - MPHSW. The main responsibility of guiding and monitoring
      the construction and implementation of the waste management plan falls on the
      local health and environmental protection authorities. This paper presents a
      model for a questionnaire to be used by the local authorities for analyzing the
      MPHSW of the health services in their respective jurisdictions. The result of
      this analysis (including graphs and tables with the percentages of questions
      fitting into each criterion set in advance) will be returned to the health
      institution with precise instructions for improving the quality of the plan. The
      necessary software is easily available and allows adapting the questionnaire to
      the conditions and needs of each municipality. The model provides parameters
      enabling the involved authorities to direct their capacity-building actions,
      allows quick evaluation of the MPHSWs and is easily updated.

PMID- 18833373
TI  - [Waste over history: perceptions about residues].
AB  - This article describes how Man, over history, felt about the residues produced by
      human activity. The text is divided into three parts: In the first part it tells
      the story of the black plague pandemic during the XIV century, showing how this
      disease was associated with the residues produced by the human body. In the
      second part it explains how the first notions of waste were, and still are,
      related to dirt, disease and death. Finally, in the third part, it describes the
      first measures of hygiene in the Renaissance and refers to the first public
      health actions at the beginning of the XX century, starting to combat the agents
      of infectious diseases and their vectors.

PMID- 18833374
TI  - [The trajectory of a public service for alcohol and drug addicts in Vitoria: the
      case of the CPTT].
AB  - The aim of this case study is to analyze the Center for Prevention and Treatment
      of Alcohol and Drug Addiction (CPTT)/Psychosocial Care Center in Drugs and
      Alcohol (CAPS ad), and to reflect about the implementation process of the local
      addiction recovery policy for drug users and alcoholics. A document research was
      performed using as sources the CPTTs mid-year/annual and/or management reports
      and articles about the service. Data were analyzed using a priori and a
      posteriori content analysis. The CPTT, a health service of the government of the
      city of Vitoria, was created in 1992 as a psychosocial service. The services
      provided by the CPTT include individual care, daily group activities and
      reception and follow-up groups. Today, the situation in the CPTT is characterized
      by precarious employment relations for most of the professionals working there.
      The trajectory of the implementation of the CPTT in the city of Vitoria expresses
      two contradictory features: on one hand the advances made in the implementation
      of the public policy for prevention and treatment of drug and alcohol abuse, and
      on the other hand the challenge posed by the lack of a human resources policy
      capable of putting in effect the advances proposed by the policy.

PMID- 18833375
TI  - [The touched masculinity: a discussion about the digital rectal exam for prostate
      cancer prevention].
AB  - The present study aims at analyzing the meanings attributed to the digital rectal
      exam, seeking to problematize questions underlying the masculine discourse on the
      basis of aspects of the hegemonic masculinity model. Semi-structured interviews
      were held with 28 men in the city of Rio de Janeiro, in 2004. Among the main
      results is the idea that the digital rectal exam is something that violates an
      interdicted space, something that compromises the current understanding of
      masculinity, shall say, the digital rectal exam does not only affect the
      prostate, it also affects the masculinity, puts it to shame. We conclude that for
      understanding and problematizing the questions related to the prostate cancer
      prevention in special, and to the question of taking care of oneself from the
      masculine perspective in general, we need to consider the structural and symbolic
      aspects that underlie these questions.

PMID- 18833376
TI  - [Dental caries and need for dental care among the Baniwa Indians, Rio Negro,
      Amazonas].
AB  - Epidemiologic research conducted with Indian communities in Brazil has shown
      strong correlation between the deterioration of their oral health and the
      consumption of industrial products, sugar in particular, added to the lack of
      structure of oral health care. This study was carried out among the Baniwa
      Indians from the Tunui-Cachoeira region, Sao Gabriel da Cachoeira, Northwestern
      Amazon, Brazil. A cross-sectional survey was conducted according to the criteria
      established by the WHO, focusing on dental caries and need for dental treatment.
      A total of 590 individuals were examined (49.2% of the population older than 2
      years). The mean numbers of teeth with caries were 6.0, 8.2 and 22.1 in the age
      groups 12-14, 15-19 and more than 50 years respectively. In children with
      deciduous dentition the highest mean value of decayed, missing and filled teeth
      (5.3) was observed in children age 5. From the total of examined people, 73.6%
      showed some need for surgery-restoration. The individuals between 15-19 years of
      age show the highest need for restorations. The DFMT index for the Baniwa can be
      considered high. The results show that it is necessary to expand public health
      control measures related to oral heath, taking into consideration the complex
      socio-cultural reality of the Northwestern Amazon region.

PMID- 18833379
TI  - Young people's blood alcohol concentration and the alcohol consumption city law,
      Brazil.
AB  - The paper assesses blood alcohol concentration and risk behaviors for traffic
      accidents before and after the implementation of a law which prohibits the use of
      alcoholic beverages on city gas stations. In Porto Alegre, Southern Brazil, young
      people go out at night and drive to gas station convenience stores to buy
      alcoholic beverages which are consumed on the premises of parking lots in gas
      stations. Data were obtained from self-administered questionnaires and breath
      analyzers in two cross-sectional collections with purposive samples of youngsters
      in May and July 2006 (n=62, and n=50, respectively). There were no significant
      differences between the groups before and after the city law was passed. Blood
      alcohol concentration greater than 0.06% was found in 35.5% of pre-law group and
      40% of post-law group (p=0.62). Results point out heavy alcohol use in both
      groups, which did not change after the law was passed.

PMID- 18833380
TI  - Sensitivity of probabilistic record linkage for reported birth identification:
      Pro-Saude Study.
AB  - The objective of the study was to evaluate the sensitivity of probabilistic
      record linkage for reported birth identification. Data from the Pro-Saude Study
      cohort population were used comprising technical-administrative staff at a
      university in Rio de Janeiro, Brazil, in 1999. A total of 92 records of subjects
      were linked to the database of the Brazilian Information System on Live Births
      (SINASC) using RecLink II program. Both reduced and amplified strategies of
      clerical review were used. The sensitivity for birth identification with the
      reduced strategy was 60.9%, while with the amplified strategy was 72.8%. The
      limited number of fields available and the high proportion of homonymous names
      were major obstacles for the attainment of more accurate results.

PMID- 18833381
TI  - Profile of tuberculosis patients progressing to death, city of Sao Paulo, Brazil,
      2002.
AB  - OBJECTIVE: To profile adult patients dying of tuberculosis in the city of Sao
      Paulo with respect to biological, environmental and institutional factors.
      METHODS: Descriptive study covering all tuberculosis deaths (N=416) among
      individuals aged over 15 years in 2002. Data were obtained from hospital records,
      the local Mortality Information System, Coroner's Service, and tuberculosis
      Surveillance System. The estimates of relative risk and 95% confidence intervals
      (95% CI) were based on the reference group, i.e., females aged 15 to 29 years,
      originally from the State of Sao Paulo (Brazil). A comparative analysis was
      conducted using Pearson's chi-square test and Fisher's exact test for categorical
      variables and Kruskal-Wallis test for continuous variables. RESULTS: Of all
      tuberculosis deaths identified, 78% had pulmonary form. Tuberculosis diagnosis
      was made after death in 30% and in primary health care units in 14%. Of them, 44%
      had not started treatment; 49% were not notified; and 76% were men. The median
      age was 51 years; 52% had up to four years of schooling; 4% were probably living
      in the streets. Mortality rate increased with age; it was 5.0/100,000 for the
      entire city, ranging between zero to 35 according to the district. Previous
      treatment was reported for 82 out of 232 patients, and of them, 41 defaulted
      treatment. Diabetes (16%), chronic obstructive pulmonary disease (19%), HIV
      infection (11%), smoking (71%), and alcohol abuse (64%) were also reported.
      CONCLUSIONS: Adult males over 50, migrants and living in lower Human Development
      Index districts were more likely to die of tuberculosis. Low schooling and
      comorbidities are relevant characteristics. Low involvement of primary care units
      in tuberculosis diagnosis and high underreporting of cases were also seen.

PMID- 18833382
TI  - Alcohol consumption among victims of external causes in a university general
      hospital.
AB  - OBJECTIVE: To estimate frequency of alcohol consumption among victims of external
      causes cared for in a hospital. METHODS: Study performed with victims cared for
      in a university general hospital in the city of Uberlandia (Southeastern Brazil),
      between February and August 2004. Blood alcohol content was determined from 85
      patients in the emergency room. Other 301 patients, hospitalized in the
      outpatient clinics, were interviewed about possible alcohol consumption prior to
      trauma. The Cut-down, Annoyed by criticism, Guilty and Eye-opener (CAGE)
      questionnaire was applied in both groups. Fisher's exact test was employed to
      compare frequencies. RESULTS: Blood alcohol content was positive among 31.8% of
      patients tested, who most frequently required hospitalization (70.4% versus
      37.9%; p<0.05). Proportionately, positive blood alcohol content was more frequent
      (p<0.05) among victims of physical aggression (57.1%) than fall victims (18.2%)
      or those of traffic accidents (29.3%). In outpatient clinics, 29.9% of patients
      mentioned alcohol consumption, proportionately more frequent (p<0.01) among
      victims of physical aggression (67.4%) than traffic accident victims (27.8%) or
      fall victims (19.3%). Among those who had drunk alcohol and were approached in
      the emergency room or in the outpatient clinics, the following was observed: the
      majority was male (85.2% and 80.4%), the occurrence of trauma was higher (p<0.05)
      on weekends (63% and 57.8%) and at night (59.3% and 57.8%), and the CAGE
      questionnaire was positive among 81.5% and 82.2% of them. CONCLUSIONS: About a
      third of patients had drunk alcoholic beverages prior to trauma and the majority
      of them were male. Proportionately, previous alcohol consumption was more
      frequent among patients who were victims of violence. CAGE results show that most
      patients, victims of external causes after alcohol consumption, were not
      occasional drinkers, but probably chronic users or alcoholics.

PMID- 18833383
TI  - HIV/AIDS risk among female sex workers who use crack in Southern Brazil.
AB  - OBJECTIVE: To understand the social context of female sex workers who use crack
      and its impact on HIV/AIDS risk behaviors. METHODODOLOGICAL PROCEDURES:
      Qualitative study carried out in Foz do Iguacu, Southern Brazil, in 2003. Twenty
      six in-depth interviews and two focus groups were carried out with female
      commercial sex workers who frequently use crack. In-depth interviews with health
      providers, community leaders and public policy managers, as well as field
      observations were also conducted. Transcript data was entered into Atlas.ti
      software and grounded theory methodology was used to analyze the data and develop
      a conceptual model as a result of this study. ANALYSIS OF RESULTS: Female sex
      workers who use crack had low self-perceived HIV risk in spite of being engaged
      in risky behaviors (e.g. unprotected sex with multiple partners). Physical and
      sexual violence among clients, occasional and stable partners was widespread
      jeopardizing negotiation and consistent condom use. According to health
      providers, community leaders and public policy managers, several female sex
      workers who use crack are homeless or live in slums, and rarely have access to
      health services, voluntary counseling and testing, social support, pre-natal and
      reproductive care. CONCLUSIONS: Female sex workers who use crack experience a
      plethora of health and social problems, which apparently affect their risks for
      HIV infection. Low-threshold, user-friendly and gender-tailored interventions
      should be implemented, in order to increase the access to health and social
      support services among this population. Those initiatives might also increase
      their access to reproductive health in general, and to preventive strategies
      focusing on HIV/AIDS and other sexually transmitted infections.

PMID- 18833384
TI  - Missed opportunities for congenital syphilis and HIV perinatal transmission
      prevention.
AB  - OBJECTIVE: To estimate the prevalence of missed opportunities for congenital
      syphilis and HIV prevention in pregnant women who had access to prenatal care and
      to assess factors associated to non-testing of these infections. METHODS: Cross
      sectional study comprising a randomly selected sample of 2,145 puerperal women
      who were admitted in maternity hospitals for delivery or curettage and had
      attended at least one prenatal care visit, in Brazil between 1999 and 2000. No
      syphilis and/or anti-HIV testing during pregnancy was a marker for missed
      prevention opportunity. Women who were not tested for either or both were
      compared to those who had at least one syphilis and one anti-HIV testing
      performed during pregnancy (reference category). The prevalence of missed
      prevention opportunity was estimated for each category with 95% confidence
      intervals. Factors independently associated with missed prevention opportunity
      were assessed through multinomial logistic regression. RESULTS: The prevalence of
      missed prevention opportunity for syphilis or anti-HIV was 41.2% and 56.0%,
      respectively. The multivariate analysis showed that race/skin color (non-white),
      schooling (<8 years), marital status (single), income (<3 monthly minimum wages),
      having sex during pregnancy, history of syphilis prior to the current pregnancy,
      number of prenatal care visits (<6), and last prenatal visit before the third
      trimester of gestation were associated with an increased risk of missed
      prevention opportunity. A negative association with missed prevention opportunity
      was found between marital status (single), prenatal care site (hospital) and
      first prenatal visit in the third trimester of gestation. CONCLUSIONS: High rates
      of non-tested women indicate failures in preventive and control actions for HIV
      infection and congenital syphilis. Pregnant women have been discontinuing
      prenatal care at an early stage and are failing to undergo prenatal screening for
      HIV and syphilis.

PMID- 18833385
TI  - HIV testing among pregnant women in Brazil: rates and predictors.
AB  - OBJECTIVE: To assess rates of offering and uptake of HIV testing and their
      predictors among women who attended prenatal care. METHODS: A population-based
      cross-sectional study was conducted among postpartum women (N=2,234) who attended
      at least one prenatal care visit in 12 cities. Independent and probabilistic
      samples were selected in the cities studied. Sociodemographic data, information
      about prenatal care and access to HIV prevention interventions during the current
      pregnancy were collected. Bivariate and multivariate analyses were carried out to
      assess independent effects of the covariates on offering and uptake of HIV
      testing. Data collection took place between November 1999 and April 2000.
      RESULTS: Overall, 77.5% of the women reported undergoing HIV testing during the
      current pregnancy. Offering of HIV testing was positively associated with:
      previous knowledge about prevention of mother-to-child transmission of HIV;
      higher number of prenatal care visits; higher level of education and being white.
      HIV testing acceptance rate was 92.5%. CONCLUSIONS: The study results indicate
      that dissemination of information about prevention of mother-to-child
      transmission among women may contribute to increasing HIV testing coverage during
      pregnancy. Non-white women with lower level of education should be prioritized.
      Strategies to increase attendance of vulnerable women to prenatal care and to
      raise awareness among health care workers are of utmost importance.

PMID- 18833386
TI  - Gender-violence against the female nursing staff of a Brazilian hospital in Sao
      Paulo City.
AB  - OBJECTIVE: To estimate the occurrence of psychological, physical and sexual
      violence among female nursing staff. METHODS: This is a cross sectional study,
      conducted with a sample of 179 professionals (50 nurses and 129 nursing aides /
      nurse technicians) in a general hospital in the municipality of Sao Paulo,
      Southeastern Brazil, 2005-2006. A validated questionnaire was applied in face to
      face interviews with these professionals, conducted by trained interviewers.
      Psychological, physical and sexual forms of violence were addressed, involving
      both male and female aggressors who were classified as: intimate partners, family
      members and other aggressors such as acquaintances and strangers. A descriptive
      analysis was undertaken, in which the frequency of the occurrence of the
      different types of violence was calculated with a 95% confidence interval.
      RESULTS: The most frequent form of violence was intimate partner violence (63.7%;
      95% CI: 55.7;70.4), followed by violence perpetrated by others (45.8%; 95% CI:
      38.3;53.4) including patients and people accompanying them, colleagues within the
      field of health, head nurses, acquaintances and strangers. Family members
      occupied the third place as aggressors, (41.3%; 95% CI: 34.0;48.9), and the
      majority of these were fathers, brothers, uncles and cousins. In general, the
      nursing staff did not seek help frequently when acts of aggression occurred: only
      29.7% of those who suffered intimate partner violence; 20.3% whose aggressors
      were others and 29.3% whose aggressors were family members sought help. Those who
      did not perceive their experience as a form of violence represented 31.9% of the
      subjects interviewed. CONCLUSIONS: The rates of gender violence among female
      health professionals were important, particularly with respect to violence
      committed by intimate partners and family members. However, the proportion of
      these women who sought help was low, considering the fact that this group has a
      significant educational level.

PMID- 18833387
TI  - [Factors associated with access to health services prior to pregnancy by pregnant
      adolescents].
AB  - OBJECTIVE: To assess determinants of access to primary care services prior to
      pregnancy by pregnant adolescents. METHODS: Theory-based cross-sectional study
      conducted to examine access to heath services at five dimensions: geographic,
      economic, administrative, psychosocial and information. There were included in
      the study 200 first-time pregnant adolescents (aged 10 to 19 years) who attended
      a primary care unit in the municipality of Indaiatuba, Southeastern Brazil, in
      2003. Data was collected using a semi-structured questionnaire applied in face-to
      face interviews conducted just before their first pre-natal care visit. Data
      analyses were performed through Person's chi-square or Fisher's exact test, and
      by a multivariate logistic regression model including all five dimensions of
      access. RESULTS: More than half (63.7%) of the adolescents utilized some
      gynecological care service. Information (43.8%) or psychosocial feelings of
      embarrassment or fear (37.0%) barriers were the most frequent reasons given for
      not having sought care before. The main barrier to health service access was
      related to the psychosocial dimension, reported by 77.0% of the adolescents
      studied. CONCLUSIONS: Among all barriers to health service access, the most
      important were those related to the psychosocial dimension. There is a need for
      new strategies to facilitate access to health services by adolescents, including
      actions to reduce gender-based barriers taking into consideration
      sociodemographic characteristics of this population and the relationship they
      have with their partners.

PMID- 18833388
TI  - [Quality assessment of labor care provided in the Unified Health System in Rio de
      Janeiro, Southeastern Brazil, 1999-2001].
AB  - OBJECTIVE: Quality of labor care has been recognized as a major factor for
      prevention of obstetric complications which can lead to maternal, perinatal and
      neonatal morbidity and mortality. The objective of the study was to assess
      quality of labor care by gestational risk and type of health provider. METHODS:
      Observational, cross-sectional study of labor care provided to 574 pregnant
      women. Stratified sampling in 20 Unified Health System maternity hospitals in Rio
      de Janeiro, Brazil, was carried out between 1999 and 2001. Quality of labor care
      was assessed by gestational risk and type of health provider. Statistical
      analyses consisted of variance analysis and the analysis of difference between
      proportions. RESULTS: Of all women studied, 29.6% were classified at obstetric
      risk. Although hypertension is the main cause of maternal death in Brazil, 71.6%
      did not have their prelabor blood pressure measured. Five measures were taken on
      average per parturient and the lowest rate was found in privately insured
      hospitals (average of 2.9). As to humanized health care, only 21.4% of the
      parturients had an accompanying person on their side during labor, 75.7% were
      submitted to intravenous hydration and 24.3% to amniotomy. The single care
      related factor that varied by obstetric risk was frequency of blood pressure
      measures: high-risk parturients had their blood pressure measured twice as much
      as those low-risk women (mean 0.36 vs. 0.18 measures/h, p=0.006). CONCLUSIONS: In
      general, low-risk parturients were submitted to unnecessary interventions while
      high-risk women did not receive adequate care. As a result, there are poor
      perinatal outcomes, high cesarean rates and high maternal mortality rates, which
      do not reflect health care investments and technology available.

PMID- 18833389
TI  - Social medicalization and alternative and complementary medicine: the
      pluralization of health services in the Brazilian Unified Health System.
AB  - Social medicalization transforms people's habits, discourages them from finding
      their own solutions to certain health problems and places an excess demand on the
      Unified Health System. With regard to healthcare provision, an alternative to
      social medicalization is the pluralization of treatment provided by health
      institutions namely through the recognition and provision of alternative and
      complementary practices and medicines. The objective of the article was to
      analyze the potentials and difficulties of alternative and complementary
      practices and medicines based on clinical and institutional experiences and on
      the specialist literature. The research concludes that the potential of such a
      strategy to "demedicalize" is limited and should be included in the remit of the
      Unified Health System. The article highlights that the Biosciences retain a
      political and epistemiological hegemony over medicine and that the area of
      healthcare is dominated by market principles, whereby there is a trend towards
      the transformation of any kind of knowledge or structured practice related to
      health-illness processes into goods or procedures to be consumed, and this only
      reinforces heteronomy and medicalization.

PMID- 18833390
TI  - Burnout syndrome and common mental disorders among community-based health agents.
AB  - OBJECTIVE: To estimate the prevalence of the burnout syndrome and of common
      mental disorders among community-based health agents, also identifying associated
      factors. METHODS: A cross-sectional survey was carried out in 2006 with 141
      community-based health agents who had been working for at least six months in
      primary care units in the city of Sao Paulo (Southeastern Brazil). The
      participants answered three questionnaires: one about sociodemographic, health-
      and work-related characteristics, the Self Reporting Questionnaire, and the
      Maslach Burnout Inventory, which allows the assessment of three dimensions of the
      burnout syndrome: emotional exhaustion, depersonalization and reduced personal
      accomplishment. Multivariate logistic regression was used to examine associations
      between variables. RESULTS: Overall, 24.1% of the interviewees presented burnout
      syndrome. Moderate or high levels of emotional exhaustion, depersonalization and
      reduced personal accomplishment were observed in 70.9%, 34.0% and 47.5% of the
      participants, respectively. The prevalence of common mental disorders was 43.3%.
      Positive correlations between the three dimensions of burnout, were observed.
      Presence of common mental disorder was independently associated with higher
      levels of emotional exhaustion and reduced personal accomplishment. CONCLUSIONS:
      The high frequency of intense levels of burnout and the high prevalence of common
      mental disorders among community-based health agents point to the need of
      intervention strategies in these individuals' daily lives and of further studies
      to better understand the actual picture and the determinants of burnout.

PMID- 18833391
TI  - Translation, adaptation and construct validation of the Clock Test among elderly
      in Brazil.
AB  - OBJECTIVE: In Brazil, not many studies have investigated the validation of
      cognitive tests in the ageing population and none of them has analyzed the
      psychometric properties of Tuokko's Clock Test. The objective of the study was to
      translate and adapt the test to the Brazilian context, and to assess its
      construct validation. METHODS: This is a cross-sectional population-based study,
      involving 353 elderly patients from Juiz de Fora (Southeastern Brazil), from 2004
      2005. To assess convergent and divergent validities Pearson's correlation
      statistics was used. The Clock Test substests were correlated with theses
      reference instruments: mini-mental state examination, digits, block design to
      evaluate the convergent validity. the divergent validity was assessed by
      comparing the substests to the Center for Epidemiologic Studies Depression Scale.
      RESULTS: In the sample, 74.1% were women, aged between 63 and 107 years (73.8+/
      8.5), average schooling was 7.4 years (SD=4.7). In regard to convergent validity,
      significant correlations were found between all CT subtests and MMSE, Digits, and
      Block Design (p<0.01). As for the divergent validity, the only subtest that had
      significant association with the reference scale was the "clock setting"
      (p<0.05). CONCLUSIONS: The translated and validated Clock Test into a community
      sample of aged showed to be a brief screening instrument, with good construct
      validity when compared to other studies. Future research must investigate other
      psychometric properties, such as content and criterion validities.

PMID- 18833392
TI  - [Prevalence of falls in institutionalized elderly in Rio Grande, Southern
      Brazil].
AB  - OBJECTIVE: The increase of life expectancy in developing countries has been a
      source of concern about quality of life and well-being of elderly people,
      especially regarding falls. The objective of the study was to assess the
      prevalence of falls in institutionalized elderly and to describe factors
      associated. METHODS: Cross-sectional study carried out in the city of Rio Grande
      (Southern Brazil). A total of 180 elderly (65 years old or more), living in
      institutions were included in the study. The elderly were interviewed and a pre
      tested instrument with questions on falls was administered. In addition to a
      bivariate analysis (Wald), Poisson's regression analysis was conducted and
      prevalence ratios and 95% confidence intervals (95% CI) adjusted for confounders
      were estimated. RESULTS: The prevalence of falls among institutionalized elderly
      was 38.3%. Falls were most frequently seen at the home premises (62.3%) and
      mostly in the bedroom (23%). In the adjusted analysis, falls remained associated
      to white color skin, separated and divorced elderly, depression, and higher
      continuous use of medications. CONCLUSIONS: The study showed that the prevalence
      of falls among institutionalized elderly is high and that they can be disabling
      to this population. Although some of the associated factors are preventable,
      accidental falls still occur in settings that should be safe, such as the
      elderly's bedroom.

PMID- 18833393
TI  - [Risk factors for falls in the elderly: systematic review].
AB  - OBJECTIVE: To systematize results of prospective cohort studies on multiple risk
      factors for falls in the elderly and to assess their methodological quality.
      METHODS: Systematic review of epidemiological studies from Medline, SciELO and
      Lilacs database. We included prospective cohort studies with samples of more than
      100 subjects of both sexes, older than 64 years, and living either in the
      community or a nursing home. RESULTS: Of 726 studied identified, 15 met the
      inclusion criteria of being published between 1988 and 2005. The methodology of
      the studies varied. The main factors associated with increased risk of falls
      include: previous falls, altered gait, functional impairment, cognitive
      impairment, psychotropic medication use and excessive physical activity. Despite
      contradictory findings, being a woman at an advanced age may also be a predictor
      of falls. CONCLUSIONS: Methodological limitations were identified in prospective
      cohort studies on falls. There is a need for further studies on extrinsic
      determinants, including evaluator blinding and closer monitoring during follow-up
      with reduced time of recall.

PMID- 18833394
TI  - Increase in preterm births in Brazil: review of population-based studies.
AB  - OBJECTIVE: The greatest cause of infant mortality in Brazil is perinatal
      conditions, mostly associated with preterm delivery. The objective of the study
      was to evaluate the evolution of preterm delivery rates in Brazil. METHODS: A
      review was conducted using the Medline and Lilacs databases, including published
      studies in periodicals, thesis and dissertations since 1950. Exclusion criteria
      were: studies related to clinical trials and those with complications at
      gestation and preterm delivery and care. Inclusion criteria were: population
      based studies on prevalence of preterm delivery in Brazil, with representative
      sample of the studied population, and using primary data. Out of 71 studies
      found, analysis was carried out on 12. RESULTS: The prevalence of preterm
      delivery found ranged from 3.4% to 15.0% in the Southern and Southeastern regions
      between 1978 and 2004, with a rising trend from the 1990s onwards. Studies in the
      Northeastern region between 1984 and 1998 found prevalences of preterm delivery
      ranging from 3.8% to 10.2%, also with a rising trend. CONCLUSIONS: Data from the
      national live birth information system do not corroborate these trends. Rather,
      they show differences between the preterm rates given by this system and the
      rates measured in the studies included in this review. Because of the important
      role of preterm birth in relation to infant mortality in Brazil, it is important
      to identify the cause of these increases and to plan interventions that can
      diminish their occurrence.

PMID- 18833395
TI  - [Research: priorities to our public health].

PMID- 18833396
TI  - [Health defines priorities in research].

PMID- 18833397
TI  - Characterization of virologic failure after an initially successful 48-week
      course of antiretroviral therapy in HIV/AIDS outpatients treated in Santos,
      Brazil.
AB  - We characterized the virologic failure after an initially successful 48-week
      course of antiretroviral therapy among HIV/AIDS patients in a retrospective
      cohort study involving patients from Santos, Brazil. Patients with plasma HIV RNA
      below 500 copies/mL for 48 weeks were included. Variables analyzed included
      gender, age, level of education, marital status, mode of HIV acquisition, viral
      load, and CD4 cell count upon admission. There were 4,909 patients registered
      with the clinic, of which 669 patients met all the inclusion criteria (41.6%
      female and 58.4% male). Only 27.5% of the patients maintained undetectable viral
      loads during up to one year of follow-up. After 48 weeks, virologic failure
      occurred earlier in females and in patients first treated with an antiretroviral
      regimen other than highly active antiretroviral therapy. Patients who were
      married or had a steady partner experienced virologic failure later than did
      those who were separated or widowed. The percentage of public health clinic
      patients who maintain undetectable viral loads for a period of over a year is
      much lower than that observed among patients enrolled in clinical trials.
      Females, individuals in unstable relationships, single individuals and widowed
      individuals should be given special attention in order to improve durability of
      viral suppression.

PMID- 18833398
TI  - HIV testing during pregnancy: use of secondary data to estimate 2006 test
      coverage and prevalence in Brazil.
AB  - This paper describes a methodological proposal based on secondary data and the
      main results of the HIV-Sentinel Study among childbearing women, carried out in
      Brazil during 2006. A probabilistic sample of childbearing women was selected in
      two stages. In the first stage, 150 health establishments were selected,
      stratified by municipality size (<50,000; 50,000-399,999; 400,000+). In the
      second stage, 100-120 women were selected systematically. Data collection was
      based on HIV-test results registered in pre-natal cards and in hospital records.
      The analysis focused on coverage of HIV-testing during pregnancy and HIV
      prevalence rate. Logistic regression models were used to test inequalities in HIV
      testing coverage during pregnancy by macro-region of residence, municipality
      size, race, educational level and age group. The study included 16,158 women.
      Results were consistent with previous studies based on primary data collection.
      Among the women receiving pre-natal care with HIV-test results registered in
      their pre-natal cards, HIV prevalence was 0.41%. Coverage of HIV-testing during
      pregnancy was 62.3% in the country as a whole, but ranged from 40.6% in the
      Northeast to 85.8% in the South. Significant differences according to race,
      educational level and municipality size were also found. The proposed methodology
      is low-cost, easy to apply, and permits identification of problems in routine
      service provision, in addition to monitoring compliance with Ministry of Health
      recommendations for pre-natal care.

PMID- 18833399
TI  - The influence of HCV coinfection on clinical, immunological and virological
      responses to HAART in HIV-patients.
AB  - The potential impact of the hepatitis C virus (HCV) on clinical, immunological
      and virological responses to initial highly active antiretroviral therapy (HAART)
      of patients infected with human immunodeficiency virus (HIV) is important to
      evaluate due to the high prevalence of HIV-HCV coinfection. A historical cohort
      study was conducted among 824 HIV-infected patients starting HAART at a public
      referral service in Belo Horizonte, Brazil, to assess the impact of HCV
      seropositivity on appearance of a new AIDS-defining opportunistic illness, AIDS
      related death, suppression of viral load, and an increase in CD4-cell count. A
      total of 76 patients (9.2%) had a positive HCV test, 26 of whom (34.2%) had a
      history of intravenous drug use. In multivariate analysis, HCV seropositivity was
      associated with a smaller CD4-cell recovery (RH=0.68; 95% CI [0.49-0.92], but not
      with progression to a new AIDS-defining opportunistic illness or to AIDS-related
      death (RH=1.08; 95% CI [0.66-1.77]), nor to suppression of HIV-1 viral load
      (RH=0.81; 95% CI [0.56-1.17]) after starting HAART. These results indicate that
      although associated with a blunted CD4-cell recovery, HCV coinfection did not
      affect the morbidity or mortality related to AIDS or the virological response to
      initial HAART.

PMID- 18833400
TI  - HCV virological response during treatment of chronic hepatitis C is associated
      with liver histological improvement in patients with HCV/HIV co-infection.
AB  - Liver histological improvement after treatment for chronic hepatitis C in
      patients co-infected with human immunodeficiency virus-1 (HIV-1) has been
      described. Paired liver biopsies in twenty six HCV/HIV co-infected patients were
      compared to determine factors possibly associated with histological improvement.
      The patients were submitted to a liver biopsy before treatment for hepatitis C
      and 25 months after the end of treatment. Fragments of the liver biopsy obtained
      before and after treatment were compared regarding the following parameters:
      histological activity index (HAI) and degree of fibrosis (Knodell); intensity of
      collagen deposits (Sirius Red staining) and degree of stellate cell activation
      (alpha-smooth muscle actin labeling). The ratios of the post and pre-treatment
      variables were related through logistic regression to body mass index (BMI),
      alcohol ingestion, HCV genotype, HCV viremia, presence of hepatic iron and pre
      treatment hepatic steatosis. A negative RNA test in the 24th week of treatment
      was associated with improvement in fibrosis, collagen deposits and stellate cell
      numbers. The other variables analyzed did not correlate to an improvement in
      hepatic histology after hepatitis C treatment. Reduction in HCV viremia during
      treatment may result in reduced hepatic fibrosis even in patients without a
      sustained virological response.

PMID- 18833401
TI  - Epstein-Barr virus nuclear antigen-2 detection and typing in immunocompromised
      children correlated with lymphoproliferative disorder biopsy findings.
AB  - Epstein-Barr virus (EBV), the causative agent of infectious mononucleosis, plays
      a significant role as a cofactor in the process of tumorigenesis, and has
      consistently been associated with a variety of malignancies especially in
      immunocompromised patients. Forty-four children and adolescents (21 liver
      transplant patients, 7 heart transplant, 5 AIDS, 3 autoimmune hepatitis, 2
      nephritic syndromes, 2 medullar aplasia, 2 primary immunodeficiency disorder
      patients, 1 thrombocytopenic purpura and 1 systemic lupus erythematosus)
      presenting with chronic active EBV infection (VCA-IgM persistently positive; VCA
      IgG > 20 AU/mL and positive IgG _ EBNA) had peripheral blood samples obtained
      during clinically characterized EBV reactivation episodes. DNA samples were
      amplified in order to detect and type EBV on the basis of the EBNA-2 sequence
      (EBNA2 protein is essential for EBV-driven immortalization of B lymphocytes).
      Although we have found a predominance of type 1 EBNA-2 virus (33/44; 75%), 10
      patients (22.73%) carried type 2 EBNA-2, and one liver transplant patient (2.27%)
      a mixture of the two types, the higher proportion of type 2 EBV, as well as the
      finding of one patient bearing the two types is in agreement with other reports
      held on lymphoproliferative disorder (LPD) patients, which analyzed tumor
      biopsies. We conclude that EBNA-2 detection and typing can be performed in
      peripheral blood samples, and the high prevalence of type 2 in our casuistic
      indicates that this population is actually at risk of developing LPD, and should
      be monitored.

PMID- 18833402
TI  - Parainfluenza virus infections in a tropical city: clinical and epidemiological
      aspects.
AB  - Little information on the epidemiology and clinical characteristics of human
      parainfluenza virus (HPIV) infections, especially in children from tropical
      countries, has been published. The aim of this study was to determine the
      frequency of HPIV infections in children attended at a large hospital in
      Fortaleza in Northeast Brazil, and describe seasonal patterns, clinical and
      epidemiological characteristics of these infections. From January 2001 to
      December 2006, a total of 3070 nasopharyngeal aspirates collected from children
      were screened by indirect immunofluorescence for human parainfluenza viruses 1,
      2, and 3 (HPIV-1, 2 and 3) and other respiratory viruses. Viral antigens were
      identified in 933 samples and HPIV in 117. The frequency of HPIV-3, HPIV-1 and
      HPIV-2 was of 83.76%, 11.96% and 4.27%, respectively. Only HPIV-3 showed a
      seasonal occurrence, with most cases observed from September to November, and
      with an inverse relationship to the rainy season. Most HPIV-3 infections seen in
      outpatients were diagnosed as upper respiratory tract infections.

PMID- 18833403
TI  - Indications of a new antibiotic in clinical practice: results of the tigecycline
      initial use registry.
AB  - Tigecycline is the first of a new class of antibiotics named glycylcyclines and
      it was approved for the treatment of complicated intra-abdominal infections and
      complicated skin and skin structure infections. Notwithstanding this,
      tigecycline's pharmacological and microbiological profile which includes
      multidrug-resistant pathogens encourages physicians' use of the drug in other
      infections. We analyzed, during the first months after its launch, the
      tigecycline prescriptions for 113 patients in 12 institutions. Twenty-five
      patients (22%) received tigecycline for approved indications, and 88 (78%) for
      "off label" indications (56% with scientific support and 22% with limited or
      without any scientific support). The most frequent "off label" use was ventilator
      associated pneumonia (VAP) (63 patients). The etiology of infections was
      established in 105 patients (93%). MDR-Acinetobacter spp. was the microorganism
      most frequently isolated (50% of the cases). Overall, attending physicians
      reported clinical success in 86 of the 113 patients (76%). Our study shows that
      the "off label" use of tigecycline is frequent, especially in VAP. due to MDR
      Acinetobacter spp., where the therapeutic options are limited (eg: colistin).
      Physicians must evaluate the benefits/risks of using this antibiotic for
      indications that lack rigorous scientific support.

PMID- 18833404
TI  - Intravenous azithromycin plus ceftriaxone followed by oral azithromycin for the
      treatment of inpatients with community-acquired pneumonia: an open-label, non
      comparative multicenter trial.
AB  - Community-Acquired Pneumonia (CAP) is a major public health problem. In Brazil it
      has been estimated that 2,000,000 people are affected by CAP every year. Of
      those, 780,000 are admitted to hospital, and 30,000 have death as the outcome.
      This is an open-label, non-comparative study with the purpose of evaluating
      efficacy, safety, and tolerability levels of IV azithromycin (IVA) and IV
      ceftriaxone (IVC), followed by oral azithromycin (OA) for the treatment of
      inpatients with mild to severe CAP. Eighty-six patients (mean age 56.6 +/- 19.8)
      were administered IVA (500 mg/day) and IVC (1g/day) for 2 to 5 days, followed by
      AO (500 mg/day) to complete a total of 10 days. At the end of treatment (EOT) and
      after 30 days (End of Study--EOS) the medication was evaluated clinically,
      microbiologically and for tolerability levels. Out of the total 86-patient
      population, 62 (72.1%) completed the study. At the end of treatment, 95.2% (CI95:
      88.9% - 100%) reported cure or clinical improvement; at the end of the study,
      that figure was 88.9% (CI95: 74.1% - 91.7%). Out of the 86 patients enrolled in
      the study, 15 were microbiologically evaluable for bacteriological response. Of
      those, 6 reported pathogen eradication at the end of therapy (40%), and 8
      reported presumed eradication (53.3%). At end of study evaluation, 9 patients
      showed pathogen eradication (50%), and 7 showed presumed eradication (38.89%).
      Therefore, negative cultures were obtained from 93.3% of the patients at EOT, and
      from 88.9% at the end of the study. One patient (6.67% of patient population)
      reported presumed microbiological resistance. At study end, 2 patients (11.11%)
      still reported undetermined culture. Uncontrollable vomiting and worsening
      pneumonia condition were reported by 2.3% of patients. Discussion and Conclusion
      Treatment based on the administration of IV azithromycin associated to
      ceftriaxone and followed by oral azithromycin proved to be efficacious and well
      tolerated in the treatment of Brazilian inpatients with CAP.

PMID- 18833405
TI  - Evaluation of the accuracy of various phenotypic tests to detect oxacillin
      resistance in coagulase-negative staphylococci.
AB  - In this study, we determined the accuracy of phenotypic tests (cefoxitin agar
      dilution, 30 microg-cefoxitin and 1 microg-oxacillin disks) to detect the
      oxacillin resistance/mecA gene among coagulase-negative staphylococci (CoNS)
      isolates. The presence of the mecA gene was detected by PCR technique (gold
      standard). A total of 176 CoNS isolates from blood of hospitalized patients were
      evaluated. Of these, 138 (78.4%) harbored the mecA gene. Using 30 microg
      cefoxitin and 1 microg-oxacillin disks we obtained 100 and 98.3% accuracy,
      respectively. In addition, when cefoxitin was used as marker in an agar dilution
      method, the higher accuracy (99.4%) was established with 8 mg cefoxitin per mL
      breakpoint. Thus, despite of the agar dilution method using cefoxitin as a marker
      not being standard for this detection, our results suggested that it is an
      excellent alternative to detect the oxacillin resistance/mecA gene among CoNS
      isolates.

PMID- 18833406
TI  - Type IV SCCmec found in decade old Brazilian MRSA isolates.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) commonly causes infection in
      hospitalized patients. Since its appearance in the 1960s, the SCCmec has evolved
      throughout the years into 5 different types (I-V), each bearing a different set
      of genes. Infection with MRSA SCCmec types I, II or III is almost exclusively
      restricted to hospitalised patients. However, recently, community acquired MRSA
      (CA-MRSA) infections have been reported with increasing frequency, usually caused
      by a type IV SCCmec MRSA in nosocomial settings. We studied the prevalence of
      SCCmec types in 50 nosocomial strains collected from 1995 to 1999. The SCCmec
      complex type and presence of Panton-Valentine leukocidin (PVL) were determined by
      PCR. Strains had been previously typed by PFGE and were now typed by MLST. We
      found that 3 of the isolates studied bore a type IVc SCCmec all having different
      PFGE and MLST profiles (ST3, ST5 and ST88). All strains bearing a type III SCCmec
      belonged to MLST ST239 (Brazilian/Iberian clone). Only the strain which presented
      the ST5 profile bore the pvl gene. The type IVc SCCmec strains presented
      relatively lower levels of resistance to oxacillin in comparison to the type III
      SCCmec strains. The pattern of dissemination of the type IV SCCmec remains to be
      elucidated. The finding of strains carrying a type IV SCCmec in the present study
      among strains isolated at least 7 years ago indicates that clones bearing a type
      IV SCCmec have been present in Brazil for quite some time, and must have gone by
      undetected.

PMID- 18833407
TI  - Bacterial contamination in milk kitchens in pediatric hospitals in Salvador,
      Brazil.
AB  - Milk may represent an important source of infectious agents to hospitalized
      pediatric patients. To describe the bacterial microflora isolated from the hands,
      stools, pharynx of all workers at milk kitchens in pediatric hospitals in the
      city of Salvador, Brazil, as well as in the formulas prepared by them, we carried
      out this cross-sectional study with all 91 workers from the 20 milk kitchens of
      all the public and private hospitals in Salvador, Brazil. Hand and pharynx swabs
      and stool samples were collected from all workers, as well as samples of the milk
      and formulas delivered by the kitchens. All samples were cultured for the
      detection of pathogenic and non-pathogenic bacteria. Pathogenic bacteria were
      isolated from 20 (22.0%) and 8 (8.8%) cultures of the hands and pharynx of the
      workers, respectively. No pathogenic bacteria were isolated from stool samples.
      Pathogenic bacteria were isolated from 17 (18.7%) milk samples. The prevalence of
      pathogenic bacteria in hand swabs was significantly higher in workers from public
      (37.8%) than from private (6.5%) hospitals (prevalence ratio [PR]=5.8; p<0.01).
      Pathogenic bacteria were isolated from two (4.4%) workers from public hospitals
      and six (13.0%) workers from private hospitals (PR=0.38; p=0.27). Pathogenic
      bacteria were isolated from 11 (24.4%) milk samples from public hospitals and 6
      (13.0%) from private hospitals (PR=1.9; p=0.16). A high prevalence of
      contamination was found, mainly on the hands of workers on units for manipulation
      of milk. Preventive efforts should be intensified and focus primarily on
      effective hand washing and continuous work supervision.

PMID- 18833408
TI  - Correlation between serum tumor necrosis factor alpha levels and clinical
      severity of tuberculosis.
AB  - This study verified the correlation between the serum levels of TNF alpha and
      different clinical forms of tuberculosis. We described a group of 24 patients
      presenting several clinical forms of tuberculosis and a control group of 13
      healthy individuals. The levels of TNF alpha were measured by bioassay method.
      The levels of TNF-alpha had significant differences between the tuberculosis and
      control groups. The patients with abnormal chest X-Ray findings had higher TNF
      alpha levels (15328.48 +/- 4602.19 pg/mL) when compared to patients with normal X
      Rays (3353.18 +/- 1495.29 pg/mL) (p<0.05). Patients that lost weight had higher
      TNF alpha levels (15468.54 +/- 4580.54 pg/mL) than those that didn't loose weight
      (2904.98 +/- 1367.89) (p<0.05). The levels of TNF alpha were higher in patients
      with a positive PPD skin test than in those with a negative PPD test (p<0.05).
      There was a positive correlation between patients' clinical severity and the
      serum levels of TNF alpha. In patients with successive measurements of TNF alpha,
      we observed that there was a drop in cytokine levels, and also a clinical
      improvement concomitantly. We concluded that there was a correlation between
      serum TNF alpha levels and chest X-Ray alterations, loss of weight, positive PPD
      skin test and clinical severity in patients with tuberculosis. There was evidence
      of a worse clinical outcome in patients with tuberculosis that presented higher
      TNF alpha serum levels.

PMID- 18833409
TI  - Serodiagnosis of tuberculosis: specific detection of free and complex-dissociated
      antibodies anti-mycobacterium tuberculosis recombinant antigens.
AB  - The diagnostic test characteristics of detecting free and complex-dissociated IgG
      to three recombinant antigens of Mycobacterium tuberculosis (38-kDa, Ag16 and
      Ag85B), singly and in combination, were evaluated in sera from 161 tuberculous
      patients [smear-positive pulmonary TB (50), smear-negative pulmonary TB (pTBsm-)
      (60) and extrapulmonary TB (51)) and 214 control patients (mycobacteriosis (14),
      mycoses(14), leprosy(4), other underlying diseases (82) and healthy people
      (100)]. The individual antigens ranged from 25% to 42% in sensitivity and from
      93% to 96% in specificity, while considering free IgG response. Addition of
      complex-dissociated antibodies against each individual antigen improved the
      sensitivity up to 55%. The number and levels of specific antibodies varied
      greatly from individual to individual. Combination of individual results for free
      and complex-dissociated IgG to 38-kDa, Ag16 and Ag85B offered 76% sensitivity and
      83% specificity. When the three antigens were placed in the same well, the
      sensitivity was lower than that expected on the basis of single antigen (63%) but
      with a good specificity (95%), even in the group of mycobacteriosis or mycoses.
      The highest contribution of complex-dissociated IgG results to free IgG results
      was seen for the diagnosis of pTBsm- patients. In conclusion, although neither
      single recombinant antigen was reactive with most sera from TB patients even
      after the measurement of both free and complex-dissociated antibodies, the use of
      multi-antigen cocktails improved the diagnostic utility of the ELISA assay,
      allowing the identification of almost 70% of pTBsm-, with a high level of
      specificity; the use of additional, well selected antigens should lead to the
      detection of almost all patients with TB.

PMID- 18833410
TI  - Polymerase chain reaction as a useful and simple tool for rapid diagnosis of
      tuberculous meningitis in a Brazilian tertiary care hospital.
AB  - Meningitis is a severe and potentially fatal form of tuberculosis. The diagnostic
      workup involves detection of acid-fast bacilli (AFB) in the cerebrospinal fluid
      (CSF) by microscopy or culture, however, the difficulty in detecting the organism
      poses a challenge to diagnosis. The use of the polymerase chain reaction (PCR) in
      the diagnostic approach to Mycobacterium tuberculosis (MTB) meningitis has been
      reported as a fast and accurate method, with several commercial kits available.
      As an alternative, some institutions have been developing inexpensive in house
      assays. In our institution, we use an in house PCR for tuberculosis. We analyzed
      the performance of our PCR for the diagnosis of MTB meningitis in 148 consecutive
      patients, using MTB culture as gold standard. The sensitivity and specificity of
      CSF PCR for the diagnosis of MTB meningitis was 50% and 98.6% respectively with a
      concordance with CSF mycobacterial culture of 96% (Kappa=0.52). In contrast to
      CSF cultures for MTB, our PCR test is a fast, simple and inexpensive tool to
      diagnose tuberculous meningitis with a performance similar to that obtained with
      the available commercial kits.

PMID- 18833411
TI  - Renal involvement in leptospirosis--new insights into pathophysiology and
      treatment.
AB  - Acute renal failure (ARF) is one of the most common complications of
      leptospirosis although the causal mechanisms are still unclear. Diverse
      mechanisms are implicated in leptospiral nephropathy and new data supports the
      role of peculiar ion transport defects. Besides antibiotic therapy, ARF
      management in leptospirosis requires dialytic therapy which is most efficient
      when started early. Dialysis is the standard supportive therapy even though
      recent evidence suggests clinical benefit from alternative treatments such as
      plasmapheresis and hemofiltration. Renal recovery is achieved soon after clinical
      improvement. The comprehension of the primary mechanisms of renal dysfunction
      will be helpful in the development of additional therapeutic tools for improving
      supportive therapy for leptospiral nephropathy. This review discusses new
      insights into mechanisms implicated in leptospiral ARF and recent advances in
      treatment.

PMID- 18833412
TI  - Hepatotropic viruses in the Brazilian Amazon: a health threat.
AB  - Viral Hepatitis B, C and D are a serious public health problem in Brazil and
      other South American countries, mainly in the Amazonian region. Despite the
      paucity of clinical and epidemiological studies, a high prevalence of Hepatitis
      viruses has often been described in this area. Genotype F of Hepatitis B and
      Genotype III of Hepatitis D have been found to be quite prevalent in this area
      and preliminary studies have implicated both genotypes in carcinogenesis and
      peculiar pathogenic liver mechanisms. Initial epidemiological studies have
      further demonstrated a high prevalence of Hepatitis C in the western Brazilian
      Amazon. The geographic, cultural, ethnic and environmental aspects of this region
      may favor hepatotropic virus dissemination, as well as rendering difficult the
      implementation of governmental programs in the treatment of patients and
      prevention of disease dissemination.

PMID- 18833413
TI  - Primary sternal osteomyelitis caused by Nocardia nova: case report and literature
      review.
AB  - A 51 year old woman without significant past medical history or risk factors for
      Nocardia infection developed primary Nocardia nova sternal osteomyelitis with
      mediastinal abscess, diagnosed with open biopsy. She required prolonged
      antibiotic therapy and had a favorable outcome. Primary sternal osteomyelitis
      develops in the absence of a contiguous focus of infection, as opposed to
      secondary sternal osteomyelitis, which is usually a complication of sternotomy.
      Staphylococcus aureus probably still is the most common cause of both forms of
      sternal osteomyelitis. Nocardia species invade humans usually through the
      respiratory tract and can cause a variety of localized infections through the
      hematogenous route. Pulmonary involvement may or may not coexist.
      Immunosuppressed patients are more prone to infection by Nocardia species,
      although cases involving seemingly immunocompetent patients are not rare. This is
      the first reported case in the English literature of primary sternal
      osteomyelitis due to Nocardia nova or any other Nocardia species.

PMID- 18833414
TI  - Disseminated infection due to Mycobacterium chelonae with scleritis,
      spondylodiscitis and spinal epidural abscess.
AB  - Mycobacteria other than tuberculosis (MOTT) have a low incidence as pathogens in
      human pathology. The most frequent clinical expression is the disseminated
      disease in subjects with compromised cellular immunity. Bacteriological
      characteristics in culture can generate confusion with other pathogens, which
      delays the appropriate diagnosis and treatment. We present a case of a
      disseminated infection due to Mycobacterium chelonae with scleritis,
      spondylodiscitis and spinal epidural abscess in a man with a medical background
      of cellular immunity deficit induced by therapeutic drugs. The antibiotic scheme
      of twenty-one weeks, during the follow-up period, controlled the infection,
      however, the optimum duration of treatment has not been established.

PMID- 18833415
TI  - [RBP is the Latin American medical journal with the highest Impact Factor].

PMID- 18833416
TI  - The impact of urban violence on mental health.

PMID- 18833418
TI  - Prevalence and correlates of physical fighting among school-going adolescents in
      Santiago, Chile.
AB  - OBJECTIVE: There is a growing interest in injury as a public health issue across
      the world. There is paucity of data on the prevalence and social correlates of
      non-fatal interpersonal violence in low- and middle-income income nations. The
      objective of this study was to estimate the prevalence of, and associated factors
      for physical fighting among school-going adolescents in Santiago, Chile. METHOD:
      We conducted a secondary analysis of the Chilean Global School-Based Health
      Survey conducted in 2004 in Santiago. We aimed to assess the prevalence and
      social correlates of having been involved in a physical fight in the prior 12
      months. RESULTS: Of the 2111 respondents, 40.7% (54.3% males and 26.6% females)
      reported having been in a physical fight in the prior 12 months. Males were more
      likely to have been in a physical fight than females [OR = 3.89, 95% CI (3.11,
      4.85)]. Substance use (cigarette smoking, drinking alcohol, and using drugs) and
      bullying victimization were positively associated with fighting [OR = 3.05, 95%
      CI (2.40, 3.87) for substance use, and OR = 1.65, 95% CI (1.32, 2.05) for
      bullying]. Parental supervision was negatively associated with physical fighting
      [OR = 0.62, 95% CI (0.50, 0.78)]. CONCLUSION: We have estimated the prevalence of
      having engaged in a physical fight among in-school adolescents in Santiago,
      Chile. We have found that the prevalence is similar to what has been reported in
      diverse settings in Africa, Europe and North America.

PMID- 18833417
TI  - The Brazilian Research Consortium on Obsessive-Compulsive Spectrum Disorders:
      recruitment, assessment instruments, methods for the development of multicenter
      collaborative studies and preliminary results.
AB  - OBJECTIVE: To describe the recruitment of patients, assessment instruments,
      implementation, methods and preliminary results of The Brazilian Research
      Consortium on Obsessive-Compulsive Spectrum Disorders, which includes seven
      university sites. METHOD: This cross-sectional study included a comprehensive
      clinical assessment including semi-structured interviews (sociodemographic data,
      medical and psychiatric history, disease course and comorbid psychiatric
      diagnoses), and instruments to assess obsessive-compulsive (Yale-Brown Obsessive
      Compulsive Scale and Dimensional Yale-Brown Obsessive-Compulsive Scale),
      depressive (Beck Depression Inventory) and anxious (Beck Anxiety Inventory)
      symptoms, sensory phenomena (Universidade de Sao Paulo Sensory Phenomena Scale),
      insight (Brown Assessment Beliefs Scale), tics (Yale Global Tics Severity Scale)
      and quality of life (Medical Outcome Quality of Life Scale Short-form-36 and
      Social Assessment Scale). The raters' training consisted of watching at least
      five videotaped interviews and interviewing five patients with an expert
      researcher before interviewing patients alone. The reliability between all
      leaders for the most important instruments (Structured Clinical Interview for DSM
      IV, Dimensional Yale-Brown Obsessive-Compulsive Scale, Universidade de Sao Paulo
      Sensory Phenomena Scale) was measured after six complete interviews. RESULTS:
      Inter-rater reliability was 96%. By March 2008, 630 obsessive-compulsive disorder
      patients had been systematically evaluated. Mean age (+/-SE) was 34.7 (+/-0.51),
      56.3% were female, and 84.6% Caucasian. The most prevalent obsessive compulsive
      symptom dimensions were symmetry and contamination. The most common comorbidities
      were major depression, generalized anxiety and social anxiety disorder. The most
      common DSM-IV impulsive control disorder was skin picking. CONCLUSION: The sample
      was composed mainly by Caucasian individuals, unmarried, with some kind of
      occupational activity, mean age of 35 years, onset of obsessive-compulsive
      symptoms at 13 years of age, mild to moderate severity, mostly of symmetry,
      contamination/cleaning and comorbidity with depressive disorders. The Brazilian
      Research Consortium on Obsessive-Compulsive Spectrum Disorders has established an
      important network for standardized collaborative clinical research in obsessive
      compulsive disorder and may pave the way to similar projects aimed at integrating
      other research groups in Brazil and throughout the world.

PMID- 18833419
TI  - Administration of the Autism Behavior Checklist: agreement between parents and
      professionals' observations in two intervention contexts.
AB  - OBJECTIVE: To determine the agreement between responses on the Autism Behavior
      Checklist by mothers and healthcare professionals. METHOD: Twenty-three mothers
      of children from the autism spectrum (DSM-IV-TR, 2002) were interviewed. The
      children were part of an educational program of the Autistic Friends Association
      SP. The healthcare professionals in charge of the children at the institution
      filled out a questionnaire regarding the method for observing behavior. For
      comparison purposes, an additional 15 mothers of children from the autism
      spectrum were interviewed at the speech therapy clinic of Universidade Federal de
      Sao Paulo, and the speech therapists responsible for the children filled out the
      questionnaire on the observation method. The Kappa index was employed to obtain
      the frequency of agreement between mothers and healthcare professionals'
      observations on the overall Autism Behavior Checklist, as well as its individual
      components. The Student's t-test was used to assess differences or similarities
      between the Kappa results. RESULTS: The agreement index was low for the total
      score, with a statistically significant difference between both groups (p <
      0.001). Agreement was also low for each Autism Behavior Checklist components, but
      there was greater agreement in the group treated at the public service in the
      Language, Body and Use of Objects components (p < 0.001). CONCLUSION: There was
      disagreement between the observations in both intervention contexts, but
      agreement was better at the public service than at Autistic Friends Association.

PMID- 18833420
TI  - Cognitive impairment in a Brazilian sample of patients with bipolar disorder.
AB  - OBJECTIVE: Persistent neurocognitive deficits have been described in bipolar mood
      disorder. As far as we are aware, no study have examined whether the cognitive
      impairment is presented in the same way in a Brazilian sample. METHOD: Cognitive
      function of 66 patients with bipolar disorder (32 with depressive symptoms and 34
      euthymic) and 28 healthy subjects was examined using a complete cognitive
      battery. RESULTS: Patients with bipolar disorder presented a significantly poorer
      performance in eight of the 12 subtests when compared to healthy subjects. There
      was no significant difference between the subgroups of patients. These patients
      showed impairment in both verbal and non-verbal cognitive function. CONCLUSION:
      Cognitive impairment was found in both groups of patients with bipolar disorder.
      The findings described here suggest an overall impairment of cognitive function,
      independent of mood symptoms. This is in line with data showing that cognitive
      deficits may be a persistent characteristic of bipolar disorder.

PMID- 18833421
TI  - Staying at the crossroads: assessment of the potential of serum lithium
      monitoring in predicting an ideal lithium dose.
AB  - OBJECTIVE: Lithium has been successfully employed to treat bipolar disorder for
      decades, and recently, was shown to attenuate the symptoms of other pathologies
      such as Alzheimer's disease, Down's syndrome, ischemic processes, and glutamate
      mediated excitotoxicity. However, lithium's narrow therapeutic range limits its
      broader use. Therefore, the development of methods to better predict its dose
      becomes essential to an ideal therapy. METHOD: the performance of adult Wistar
      rats was evaluated at the open field and elevated plus maze after a six weeks
      treatment with chow supplemented with 0.255%, or 0.383% of lithium chloride, or
      normal feed. Thereafter, blood samples were collected to measure the serum
      lithium concentration. RESULTS: Animals fed with 0.255% lithium chloride
      supplemented chow presented a higher rearing frequency at the open field, and
      higher frequency of arms entrance at the elevated plus maze than animals fed with
      a 50% higher lithium dose presented. Nevertheless, both groups presented similar
      lithium plasmatic concentration. DISCUSSION: different behaviors induced by both
      lithium doses suggest that these animals had different lithium distribution in
      their brains that was not detected by lithium serum measurement. CONCLUSION:
      serum lithium concentration measurements do not seem to provide sufficient
      precision to support its use as predictive of behaviors.

PMID- 18833422
TI  - Cataract occurrence in patients treated with antipsychotic drugs.
AB  - OBJECTIVE: Typical antipsychotic drugs, mainly phenothiazines, have been
      associated with cataract formation for over forty years. Recently, there has been
      a concern about atypical antipsychotic drugs' potential for inducing this
      lenticular pathology. Accordingly, we sought to determine the cataract rate and
      other ocular side effects in patients on long-term therapy with antipsychotic
      drugs. METHOD: Eighty outpatients with DSM-IV diagnosis of schizophrenia from two
      settings who met pre determined inclusion criteria were submitted to an
      ophthalmological evaluation for ocular abnormalities with emphasis in the lens
      and cornea. They were divided into two groups: group 1 (n = 52) comprised
      patients who had been predominantly on typical antipsychotics for at least two
      years and group 2 (n = 28) patients who had been predominantly on atypical
      antipsychotics for at least two years. RESULTS: Cataract was found in 26 patients
      (33%) with predominance of anterior capsular cataract. The cataract rate among
      patients from group 1 (40%) was higher than among those from group 2 (18%).
      Visual acuity was reduced in 21 patients (26%). No changes were observed neither
      in the cornea nor in the retina. CONCLUSIONS: Patients using antipsychotic drugs
      should be submitted to a periodic ophthalmological evaluation.

PMID- 18833423
TI  - DSM-IV personality disorders in Mexico: results from a general population survey.
AB  - OBJECTIVE: This paper reports the first population estimates of prevalence and
      correlates of personality disorders in the Mexican population. METHOD:
      Personality disorders screening questions from the International Personality
      Disorder Examination were administered to a representative sample of the Mexican
      urban adult population (n = 2,362) as part of the Mexican National Comorbidity
      Survey, validated with clinical evaluations conducted in the United States. A
      multiple imputation method was then implemented to estimate prevalence and
      correlates of personality disorder in the Mexican sample. RESULTS: Multiple
      imputation method prevalence estimates were 4.6% Cluster A, 1.6% Cluster B, 2.4%
      Cluster C, and 6.1% any personality disorder. All personality disorders clusters
      were significantly comorbid with DSM-IV Axis I disorders. One in every five
      persons with an Axis I disorder in Mexico is likely to have a comorbid
      personality disorder, and almost half of those with a personality disorder are
      likely to have an Axis I disorder. CONCLUSIONS: Modest associations of
      personality disorders with impairment and strong associations with treatment
      utilization were largely accounted for by Axis I comorbidity suggesting that the
      public health significance of personality disorders lies in their comorbidity
      with, and perhaps effects upon, Axis I disorders rather than their direct effects
      on functioning and help seeking.

PMID- 18833424
TI  - Drinking patterns between men and women in two distinct Brazilian communities.
AB  - OBJECTIVE: A survey was conducted to compare gender differences in patterns of
      drinking in two stratified, urban and representative samples from two communities
      (B and RJr). METHOD: The Genacis (Gender, Alcohol, and Culture: an International
      Study) questionnaire was used. RESULTS: There were several significant
      differences in the demographics and patterns of alcohol use between these two
      samples. One had an older, more Catholic, educated, Caucasian population, with
      more women in the labor force. Data from B community showed that women and men
      had similar patterns of drinking. RJr had much higher use of alcohol among men,
      and almost 22% of those under 49 years old were binge drinkers. DISCUSSION:
      Access, smoking, income and having a heavy drinker partner were important risk
      factors for women's drinking. CONCLUSIONS: This study shows that when women's
      roles become more similar to men's, so do their drinking patterns.

PMID- 18833425
TI  - Increased oxidative stress as a mechanism for decreased BDNF levels in acute
      manic episodes.
AB  - OBJECTIVE AND METHOD: There is a growing amount of data indicating that
      alterations in brain-derived neurotrophic factor and increased oxidative stress
      may play a role in the pathophysiology of bipolar disorder. In light of recent
      evidence demonstrating that brain-derived neurotrophic factor levels are
      decreased in situations of increased oxidative stress, we have examined the
      correlation between serum thiobarbituric acid reactive substances, a measure of
      lipid peroxidation, and serum brain-derived neurotrophic factor levels in bipolar
      disorder patients during acute mania and in healthy controls. RESULTS: Serum
      thiobarbituric acid reactive substances and brain-derived neurotrophic factor
      levels were negatively correlated in bipolar disorder patients (r = -0.56; p =
      0.001), whereas no significant correlation was observed in the control group..
      CONCLUSION: These results suggest that alterations in oxidative status may be
      mechanistically associated with abnormal low levels of brain-derived neurotrophic
      factor observed in individuals with bipolar disorder.

PMID- 18833426
TI  - Personality traits and treatment outcome in obsessive-compulsive disorder.
AB  - OBJECTIVE: Comorbidity with personality disorders in obsessive-compulsive
      patients has been widely reported. About 40% of obsessive-compulsive patients do
      not respond to first line treatments. Nevertheless, there are no direct
      comparisons of personality traits between treatment-responsive and non-responsive
      patients. This study investigates differences in personality traits based on
      Cloninger's Temperament and Character Inventory scores between two groups of
      obsessive-compulsive patients classified according to treatment outcome:
      responders and non-responders. METHOD: Forty-four responsive and forty-five non
      responsive obsessive-compulsive patients were selected. Subjects were considered
      treatment-responsive (responder group) if, after having received treatment with
      any conventional therapy, they had presented at least a 40% decrease in the
      initial Yale-Brown Obsessive Compulsive Scale score, had rated "better" or "much
      better" on the Clinical Global Impressions scale; and had maintained improvement
      for at least one year. Non-responders were patients who did not achieve at least
      a 25% reduction in Yale-Brown Obsessive Compulsive Scale scores and had less than
      minimal improvement on the Clinical Global Impressions scale after having
      received treatment with at least three selective serotonin reuptake inhibitors
      (including clomipramine), and at least 20 hours of cognitive behavioral therapy.
      Personality traits were assessed using Temperament and Character Inventory.
      RESULTS: Non-responders scored lower in self-directedness and showed a trend to
      score higher in persistence than responders did. CONCLUSION: This study suggests
      that personality traits, especially self-directedness, are associated with poor
      treatment response in obsessive-compulsive patients.

PMID- 18833427
TI  - Structural magnetic resonance imaging in anxiety disorders: an update of research
      findings.
AB  - OBJECTIVE: The aim of the present report is to present a systematic and critical
      review of the more recent literature data about structural abnormalities detected
      by magnetic resonance in anxiety disorders. METHOD: A review of the literature in
      the last five years was conducted by a search of the Medline, Lilacs and SciELO
      indexing services using the following key words: "anxiety", "panic",
      "agoraphobia", "social anxiety", "posttraumatic" and "obsessive-compulsive",
      crossed one by one with "magnetic resonance", "voxel-based", "ROI" and
      "morphometry". RESULTS: We selected 134 articles and 41 of them were included in
      our review. Recent studies have shown significant morphological abnormalities in
      various brain regions of patients with anxiety disorders and healthy controls.
      Despite some apparently contradictory findings, perhaps reflecting the
      variability and limitations of the methodologies used, certain brain regions
      appear to be altered in a consistent and relatively specific manner in some
      anxiety disorders. These include the hippocampus and the anterior cingulate
      cortex in posttraumatic stress disorder and the orbitofrontal cortex in obsessive
      compulsive disorder. CONCLUSIONS: The present review indicates that structural
      neuroimaging has contributed to a better understanding of the neurobiology of
      anxiety disorders. Further development of neuroimaging techniques, better sample
      standardization and the integration of data across neuroimaging modalities may
      extend progress in this area.

PMID- 18833428
TI  - [The use of antipsychotics in patients with dementia].
AB  - OBJECTIVE: The objective of the present study is to systematically review the
      supporting evidence for the use of antipsychotics in the treatment of behavioral
      and psychological symptoms in patients with dementia, as well as the
      controversies and limitations of this prescription. We discuss the available
      evidence in the light of the high prevalence of behavioral and psychological
      symptoms of dementia in this population, along with the greater susceptibility of
      elderly patients to adverse events. METHOD: Systematic literature review of the
      use of typical and atypical antipsychotics in patients with dementia was carried
      out in the databases PubMed/Medline, Embase and SciELO. The search was limited to
      clinical trials and meta-analysis of the literature published from 1986 to 2007.
      RESULTS: Evidence drawn from randomized, double-blind, placebo controlled trials
      support the use of both typical and atypical antipsychotics in the treatment of
      behavioral symptoms of dementia, especially psychotic symptoms and abnormal
      psychomotor activity. Nevertheless, the use of these drugs in demented patients
      is not devoid of important adverse events. Although the induction of
      extrapyramidal symptoms is not as frequent or severe with atypical antipsychotics
      as it is with first-generation neuroleptics, the former drugs may particularly
      increase the risk of cerebrovascular events and death. CONCLUSION: Although
      effective, antipsychotic drugs must be prescribed cautiously in patients with
      dementia. Dose regimens, duration of treatment and a cautious assessment of risk
      benefit must be established for each patient.

PMID- 18833429
TI  - Cannabidiol: from an inactive cannabinoid to a drug with wide spectrum of action.
AB  - OBJECTIVE: The aim of this review is to describe the historical development of
      research on cannabidiol. METHOD: This review was carried out on reports drawn
      from Medline, Web of Science and SciELO. DISCUSSION: After the elucidation of the
      chemical structure of cannabidiol in 1963, the initial studies showed that
      cannabidiol was unable to mimic the effects of Cannabis. In the 1970's the number
      of publications on cannabidiol reached a first peak, having the research focused
      mainly on the interaction with delta9-THC and its antiepileptic and sedative
      effects. The following two decades showed lower degree of interest, and the
      potential therapeutic properties of cannabidiol investigated were mainly the
      anxiolytic, antipsychotic and on motor diseases effects. The last five years have
      shown a remarkable increase in publications on cannabidiol mainly stimulated by
      the discovery of its anti-inflammatory, anti-oxidative and neuroprotective
      effects. These studies have suggested a wide range of possible therapeutic
      effects of cannabidiol on several conditions, including Parkinson's disease,
      Alzheimer's disease, cerebral ischemia, diabetes, rheumatoid arthritis, other
      inflammatory diseases, nausea and cancer. CONCLUSION: In the last 45 years it has
      been possible to demonstrate that CBD has a wide range of pharmacological
      effects, many of which being of great therapeutic interest, but still waiting to
      be confirmed by clinical trials.

PMID- 18833430
TI  - Cerebellum and psychiatric disorders.
AB  - OBJECTIVE: The objective of this update article is to report structural and
      functional neuroimaging studies exploring the potential role of cerebellum in the
      pathophysiology of psychiatric disorders. METHOD: A non-systematic literature
      review was conducted by means of Medline using the following terms as a
      parameter: "cerebellum", "cerebellar vermis", "schizophrenia", "bipolar
      disorder", "depression", "anxiety disorders", "dementia" and "attention deficit
      hyperactivity disorder". The electronic search was done up to April 2008.
      DISCUSSION: Structural and functional cerebellar abnormalities have been reported
      in many psychiatric disorders, namely schizophrenia, bipolar disorder, major
      depressive disorder, anxiety disorders, dementia and attention deficit
      hyperactivity disorder. Structural magnetic resonance imaging studies have
      reported smaller total cerebellar and vermal volumes in schizophrenia, mood
      disorders and attention deficit hyperactivity disorder. Functional magnetic
      resonance imaging studies using cognitive paradigms have shown alterations in
      cerebellar activity in schizophrenia, anxiety disorders and attention deficit
      hyperactivity disorder. In dementia, the cerebellum is affected in later stages
      of the disease. CONCLUSION: Contrasting with early theories, cerebellum appears
      to play a major role in different brain functions other than balance and motor
      control, including emotional regulation and cognition. Future studies are clearly
      needed to further elucidate the role of cerebellum in both normal and
      pathological behavior, mood regulation, and cognitive functioning.

PMID- 18833431
TI  - Altered state of corporal consciousness related to alien hand syndrome and
      schizophrenic motor passivity.

PMID- 18833432
TI  - A possible case of posttraumatic obsessive-compulsive disorder.

PMID- 18833433
TI  - Group therapy for pathological love.

PMID- 18833434
TI  - [Research in psychoanalysis and psychoanalytic psychotherapy: a new tool for the
      evaluation of adherence to the technique in studies of effectiveness].

PMID- 18833435
TI  - [Brazilian child and adolescent psychiatrists task force].

PMID- 18833436
TI  - [Strategy for the management of antipsychotic-induced sexual dysfunction: a case
      report description].

PMID- 18833437
TI  - Occupational therapy must be more spread among child psychiatrists.

PMID- 18833438
TI  - [How do hyperlexic children learn to read? A study of an autistic child].

PMID- 18833439
TI  - [Combining venlafaxine and mirtazapine for the treatment of major depression with
      dysthymia--"double depression"].

PMID- 18833440
TI  - The benefits of implementing telepsychiatry in the Brazilian Mental Health
      System.

PMID- 18833444
TI  - Nursing knowledge production in tuberculosis control in Brazil.

PMID- 18833445
TI  - Does directly observed treatment ("DOTS") contribute to tuberculosis treatment
      compliance?
AB  - This is a qualitative study performed in the theoretical framework of the Theory
      of Social Determination of the Health-Disease process and the concept of
      Compliance. The goal was to analyze meanings of DOTS in compliance with
      tuberculosis treatment, according to healthcare professionals of the Technical
      Healthcare Supervision of Butanta (SUVIS), a region of the Sao Paulo City
      Healthcare Secretariat, Brazil. The project was submitted to the Ethics Committee
      of the Sao Paulo Municipal Health Secretariat. All professionals (22 people)
      developing DOTS were interviewed, including service coordinators, healthcare
      professionals and the DOTS coordinator for the region. The statements were
      analyzed with an appropriate technique for discourse analysis. The results
      appoint that the strategy presents more potentialities than limits and is
      effective regarding compliance, since it allows the professionals to welcome and
      monitor the patients, considering their needs. The importance of increasing the
      understanding of compliance is also noted, so that it can go beyond the simple
      intake of medication, integrating the care for the sick person and his or her
      necessities by transcending those restricted to the biological dimension.

PMID- 18833446
TI  - Doctoral education in nursing in Brazil.
AB  - This study aimed to present the trajectory of doctoral education in nursing in
      Brazil from 1981 to 2004. A descriptive and analytical study was carried out,
      using documents available at the Brazilian Federal Agency for Support and
      Evaluation of Graduate Education, a body responsible for the recognition,
      evaluation and coordination of graduate studies in Brazil. Data analysis revealed
      that there are 13 doctoral courses in nursing, most of which are concentrated in
      the Southeast (69.2%), and that teaching and scientific production have been
      influenced by demographic and epidemiological transitions and by historical,
      social and political movements. Knowledge production is related to Nursing Care,
      Health Management and Practices and Theoretical Foundations of Care. Doctoral
      programs have prepared leaders in the fields of education, research and public
      policy development, in health institutions as well as in public policies, health
      institutions and governmental entities.

PMID- 18833447
TI  - Hypertension among undergraduate students from Lubango, Angola.
AB  - This descriptive study aimed to investigate the prevalence of hypertension and
      its risk factors among undergraduate students in Lubango-Angola. The results
      obtained according to the health field model were: a) human biology: 61.3% were
      between 18 and 29 years old; prevalence of hypertension from 20.3 to 26.7%; 17.1%
      were overweight; 3.2% were obese; b) environment: 36.1% were exclusively
      students; 33.1% gained a family income of up to 250 dollars; c) life style: 86.2%
      practiced physical activity; 60.6% preferred salty food; 4.0% were smokers; 40.6%
      drank alcohol; d) health care: 82.8% already had their arterial pressure verified
      sometime in their life, and 65.4% did not remember the obtained value.

PMID- 18833448
TI  - Behavior, knowledge and perception of risks about sexually transmitted diseases
      in a group of people over 50 years old.
AB  - The goal was to analyze the behavior, knowledge and risk perception about
      sexually transmitted diseases / AIDS (STD/AIDS) in people over 50 years old. 165
      public servants at a State Secretary in Mato Grosso, Brazil were interviewed. The
      chi-square test and logistic regression tests were used for the analysis of risk
      perception and the behavior and knowledge variables about STD/AIDS. Most of the
      respondents were female (60.6%), 63.2 had a fixed partner, 72.4% had sexual
      relations in the past six months, and only 13.3% always wore condoms, with 21.5%
      being male and 8% female. Perception of risk was associated with non-use of
      condoms in their last sexual relation (p<0.001) and answering that anyone may
      acquire a STD/AIDS (p=0.039). The challenge of public policies is to increase
      actions, directing them to promote the health of the adult and elderly
      populations, especially regarding sexuality and vulnerability to STD/AIDS.

PMID- 18833449
TI  - Daily life of patients with chronic renal failure receiving hemodialysis
      treatment.
AB  - This analytical descriptive study aimed at assessing the perception of people
      with chronic renal failure in relation to their daily and occupational
      activities. The sample was formed by 35 men and 35 women receiving hemodialysis
      treatment with ages between 17 and 60 years. The instrument used was the SAOF
      (Self Assessment of Occupational Functioning). The data were submitted to
      statistical analysis and the areas with greater choice of the alternative "need
      to improve" were habits (20%) and values (20.5%). In these areas, the proportion
      related with difficulties was more evident regarding organization of the daily
      life, the changes of routines and the expectations about the future. Therefore,
      occupational therapy, as it presents instrumental resources to reorganize daily
      life of these patients, can contribute for their care as well as with information
      for nursing.

PMID- 18833450
TI  - The influence of social support on strengthening families of children with
      chronic renal failure.
AB  - This paper presents a study of the families of children on peritoneal dialysis,
      emphasizing the identification of social supports and networks to strengthen
      interventions aimed at health promotion. Our discussion is located in the context
      of inequalities between developed and developing countries. For this qualitative
      study, a content analysis was conducted in order to elicit themes from the raw
      data related to the lived experience of four families that have a child with
      chronic renal failure. The data were collected mainly by in-depth interviews and
      the construction of genograms and ecomaps. The identification and
      characterization of the families' social supports and networks allowed nurses and
      families to strengthen their coping mechanisms. Because families are dealing with
      severe economic problems, they need better supportive programs to guide their
      offspring to their full potential.

PMID- 18833451
TI  - Relations between nursing data collection, diagnoses and prescriptions for adult
      patients at an intensive care unit.
AB  - This descriptive, retrospective study aimed to analyze the relation between
      nursing data collection, diagnoses and prescriptions for 26 adult patients who
      were hospitalized at the intense care unit of a large teaching hospital for at
      least 24 hours. Through the analysis of medical records, 135 diagnoses and 421
      nursing prescriptions were established, and 24 different diagnosis categories and
      20 different items for prescriptions were identified. The most frequent diagnosis
      risk was that for infection, present in the medical records of 22 (84.60%)
      patients, with 175 prescriptions (42%) related to this diagnosis. The data the
      nurses collected were sufficient to establish the nursing diagnoses, and the
      majority of prescriptions (87.9%) were related to the diagnoses.

PMID- 18833452
TI  - Prevalent nursing diagnoses and interventions in the hospitalized elder care.
AB  - OBJECTIVES: to identify the prevalent nursing diagnoses (ND) in the hospitalized
      elder care; to compare the prevalent ND with the duration of hospital stay and
      with the prescribed cares for their respective diagnoses. METHOD: Transversal
      historical study carried through in Porto Alegre, RS, by analyzing patient
      records age e60 years old, interned in clinical unities of a university hospital.
      RESULTS: 1665 records were analyzed; the four prevalent NANDA nursing diagnoses-
      within 62 identified ones--were: Self-Care Deficit--Bathing/Hygiene, Imbalanced
      Nutrition--Less than Body Requirements, Risk for Infection and Ineffective
      Breathing Patterns, varying from 14 to 17 days of hospital stay. THE MAIN CARES
      WERE: aiding bed bath, communicating diet acceptance, implementing routines of
      care in venous puncture and checking respiratory pattern. CONCLUSION: four
      prevalent ND were identified with the appropriate prescribed care. However, other
      care could have been established as a priority.

PMID- 18833453
TI  - Coping strategies of ostomized individuals.
AB  - This study aimed at understanding the experience of individuals with intestinal
      diversions as regards coping with their new life conditions. The qualitative
      approach was used, involving 11 ostomized subjects. The data were collected by
      means of semi-structured interviews which were taped and later fully transcribed
      and analyzed according to Content Analysis as proposed by Bardin and the Coping
      theoretical framework . The findings in the study were evidenced by three core
      categories denominated: i did not choose it; i had to accept it and i have to
      live with the ostomy. The form to manage the condition of being ostomized was
      revealed by coping strategies which were based on both emotions and the problem
      itself. The study contributed for reflection and application of knowledge in
      assistance practice and teaching for care the ostomized.

PMID- 18833454
TI  - Validation of the ratio scale of the differents types of pain.
AB  - The main aim was to validate the ratio scale derived from the non-metric
      continuum of the intensity of the different types of pain using cross-modality
      matching. Magnitude estimation method and cross-modality matching were used with
      perceived line lengths. The study was formed by 30 outpatients from various
      specialty clinics, 30 physicians and 90 nurses. The results were: Cancer Pain,
      Myocardium Infarct Pain, Renal Colic, Burn Injury Pain, and Childbirth Labor Pain
      were regarded as the pains of greater intensity; the rank order of pain intensity
      for the different types of pain, comparing the different psychophysical methods
      used resulted in levels of significant agreement. The conclusion was that the
      relation between the magnitude estimates and cross modality matching estimates of
      the line-lengths is a power function, and the scale for the different types of
      pain is valid, stable and consistent.

PMID- 18833455
TI  - Pharmacological analgesia in neonates undergoing cardiac surgery.
AB  - The objectives of this study were to verify the frequency of pharmacological
      analgesia and the occurrence of postoperative pain in neonates undergoing cardiac
      surgery. METHODS: This is a cross-sectional study and data were collected from 30
      medical charts of neonates who underwent cardiac surgery in a private hospital in
      the city of Sao Paulo. RESULTS: The majority (96.6%) of neonates received
      analgesia: 18 (60.0%) received continuous analgesics, five (16.7%) received
      intermittent drugs, and six (20.0%) received a combination of continuous and
      intermittent analgesics. Fentanyl citrate was continuously administered to 24
      (80.0%) neonates. Intermittent dipyrone and morphine was administered to ten
      (33.3%) and one (3.3%) neonates, respectively. Pain registers were observed in 17
      (56.7%) medical charts and the occurrence of pain among neonates who received
      analgesics was 53.4%. CONCLUSION: There was no efficacy in pharmacological
      postoperative pain control in the neonates included in this study.

PMID- 18833456
TI  - Participating in a support group: experience lived by women with breast cancer.
AB  - The goal of the study was to understand the meaning of support groups in the life
      of women with breast cancer. It is a qualitative study with 30 mastectomized
      women who belonged to six support groups in the city of Fortaleza, Ceara. Data
      were collected with semi-structured interviews, organized and analyzed based on
      the interactionism concept. The results characterized the support groups as a
      mechanism to cope with the situation and to overcome the suffering derived from
      the diagnosis and treatment of the breast carcinoma. The socialization of the
      experiences facilitated the search for assistance in the support groups, since
      sharing the problems with mastectomized women was a way to preserve a high self
      esteem, have faith and overcome some difficulties. Participating in the group
      provided well-being and a differentiated care, since it was considered a way to
      know, accept and understand the disease and its cure, facilitating the
      socialization of ideas.

PMID- 18833457
TI  - Bipolar affective disorder and medication therapy: identifying barriers.
AB  - This study identified the barriers faced by people with bipolar affective
      disorder (BAD) regarding the need for continuous medication. The qualitative
      approach was used, and the methodological framework was based on the Grounded
      Theory in the light of Symbolic Interactionism. In total, of 14 people with BAD,
      who were being attended at the Outpatient Unit for Mood Disorders of a university
      hospital, and 14 relatives indicated by them participated in the study. The data
      collection was carried out through interviews and observation. Two categories
      emerged from the results, describing the barriers faced by people with BAD: to
      have affective and cognitive losses and to have several limitations. People with
      BAD feel ambivalent regarding medication adherence, as they perceive that, no
      matter the direction they take, it will lead to a context of prejudice, losses
      and limitations in various spheres of daily life.

PMID- 18833458
TI  - Indicators of healthcare results: analysis of adverse events during hospital
      stays.
AB  - This quantitative, retrospective study aimed to characterize adverse events (AE)
      in Intensive Care Units (ICU), Semi-Intensive Care Units (SCU) and Inpatient
      Units (IU), regarding nature, type, day of the week and nursing professionals /
      patient ratio at the moment of occurrence; as well as to identify nursing
      interventions after the event and AE rates. The study was performed at a private
      hospital in the city of Sao Paulo, Brazil. Two hundred twenty-nine AE were
      notified. The predominant events were related to nasogastric tubes (NGT) (57.6%),
      followed by patient fall (16.6%) and medication errors (14.8%). The nursing
      professionals /patient ratio at the moment of the event was 1:2 for the ICU, 1:3
      for the SCU and 1:4 for the IU. A similar distribution was observed for the other
      days of the week. The nursing interventions were: repositioning the NGT (83.2%)
      and communication of the occurrence to the physician in case of medication errors
      (47.6%) and falls (55.2%). The highest AE rate was related to NGT.

PMID- 18833459
TI  - Assessment of risk and incidence of falls in neurosurgical inpatients.
AB  - Neurosurgical patients may present motor, sensitive and balance impairment and
      increased risk of falling. The aim of this study was to evaluate the fall-related
      risk factors and the incidence of falls in the pre and post-operative period of
      neurosurgical patients. A prospective cohort study with a research population of
      patients undergoing elective neurosurgical procedures. Ninety-seven patients took
      part in the study. Eight (8.2%) have presented falls with a total of 12 falls
      (12.4%). In two falls (16.7%), bed side rails were down, whereas in six falls
      (50%), beds had no rails at all. There was no difference among fall-related risk
      factors during pre and the post-operative periods. We have concluded that most
      falls could have been prevented through an improvement in the hospital internal
      structure and with the introduction of a falls prevention program.

PMID- 18833460
TI  - Evaluation of products and services of a nursing library: user satisfaction.
AB  - The goal of the study was to evaluate the quality of the services provided by the
      library at the Nursing School of the University of Sao Paulo. A questionnaire
      evaluating users' satisfaction with the service was employed, covering five
      quality components: tangibles, reliability, responsiveness, assurance and
      empathy. The Satisfaction Rate was calculated through the degree of importance in
      relation to satisfaction. The analysis of the open-ended answers was quanti
      qualitative. For Reliability and Empathy, the users showed dissatisfaction with
      the training for bibliographic research and the librarian's willingness to meet
      the clients' information needs, respectively. Responsiveness did not fully
      satisfy the users, disagreeing with the providers. However, both agreed that the
      archives are outdated. Among the tangible aspects, equipment and noise were
      criticized most often. The results show that the library offers good service
      quality to its users.

PMID- 18833461
TI  - The caregiving process in the vulnerability perspective.
AB  - This theoretical article deals with the process of caregiving in the
      vulnerability perspective, whose condition leads to the need for care. The text
      analyzes this process, which is characterized by the encounter between the
      caregiver and the care receiver. The hospitalized patient is an extremely
      vulnerable being, experiencing something unique. The caregiver plays a very
      important role in reducing this situation and preserving his or her autonomy and
      dignity.

PMID- 18833462
TI  - Pharyngocutaneous fistulae after total laryngectomy: a systematic review.
AB  - Nursing care to patients after total laryngectomy should be based on scientific
      knowledge. Evidence-based practice is a type of approach that stimulates the use
      of research results in clinical practice. This study presents a systematic review
      that aimed to identify the main treatments for pharyngocutaneous fistulae after
      total laryngectomy. Articles were selected from five databases: Pubmed, Cinahl,
      Biomednet Research Tools, Cochrane Library and Lilacs. The review sample
      consisted of 37 articles. After analyzing the articles included in the review,
      results showed that conservative treatment is commonly used for pharyngocutaneous
      fistulae, recommending intensive hygiene and wound treatment. The use of research
      results in clinical practice will grant greater consistency to nurses' actions in
      care for patients with pharyngocutaneous fistulae.

PMID- 18833463
TI  - Psychocultural meanings of urinary incontinence in women: a review.
AB  - The purpose of the present study was to identify and analyze studies in health
      literature about the psychocultural meanings reported by women who experience
      urinary incontinence (UI). A bibliographical search was executed in the following
      databases: Lilacs, Medline, Pubmed and Medscape. The present review showed that
      studies note several meanings. The articles were grouped in three categories
      defined as significant: according to age experiences, cultural-religious
      experiences and experiences in self-care. The studies revealed that the degree of
      anguish and the range of the difficulties experienced are related both with age,
      ethnic group or religion and with the perception each individual has of her
      incontinence, which will lead to different levels of emotional disorders and to
      seeking (or not seeking) treatment. Besides, barriers regarding self-care are
      perceived. It is concluded that the UI may cause suffering and incontinent women
      have difficulties to deal with this problem.

PMID- 18833464
TI  - Nursing in the era of globalisation: challenges for the 21st century.
AB  - The purpose of this paper was to reflect about issues related to the processes of
      globalization and the global impacts on health, pointing out some challenges for
      Nursing in the twenty-first century. In this sense, the author outlines the forms
      and trends of globalization in the contemporary world, and the drastic impacts on
      human health and environment. To respond to the challenges of the globalized
      world, some ways are indicated, among which, the strengthening of nursing
      discipline stands out, together with some guidelines for education, research and
      Nursing care, in a local and global scope.

PMID- 18833466
TI  - Seasonality of litterfall and leaf decomposition in a cerrado site.
AB  - We investigated annual litterfall and leaf decomposition rate in a cerrado site.
      We collected woody plant litter monthly from April 2001 to March 2002 and from
      July 2003 to June 2004. We placed systematically 13 litter traps (0.5 x 0.5 m) in
      a line, 10 m one from the other. We sorted litter into 'leaves', 'stems',
      'reproductive structures', and 'miscellanea' fractions, oven-dried them at 80
      degrees C until constant mass and weighed the dry material. To assess leaf
      decomposition rate, we packed leaves recently shed by plants in litter bags. We
      placed seven sets of nine litter bags in a line, 10 m one from the other, on the
      soil surface and collected nine bags each time after 1, 2, 3, 4, 6, 9, and 12
      months. Total and leaf litter productions showed a seasonal pattern. Leaf
      litterfall was the phenological attribute that showed the strongest response to
      seasonality and drought. Decomposition was slower in the cerrado that we studied
      compared to a more closed cerrado physiognomy, reflecting their structural and
      environmental differences. Thus, decomposition rates seem to increase from open
      to closed cerrado physiognomies, probably related to an increase of humidity and
      nutrients in the soil.

PMID- 18833467
TI  - Do the seasonal forests in northeastern Brazil represent a single floristic unit?
AB  - Floristic analyses (Principal Component Analysis and Analysis of Group
      Indicators) at the genus level were employed to characterize and compare seasonal
      forest formations in northeastern Brazil. The presence--absence of 248 genera of
      woody plants occurring in 24 floristic surveys was correlated with geomorphology
      and climatic variables. The analyses were consistent and point to the existence
      of two floristic groups of seasonal forests in the region, one more closely
      related to the Atlantic Coastal Forest (mata atlantica) and the other to the
      xerophytic formations (caatinga) of the region. The driest seasonal forest group
      experiences more than 8 dry months per year and/or a total annual rainfall of
      <1000 mm, and is found on the ancient eroded peaks in the semi-arid core and on
      the western slopes of the Borborema Plateau.

PMID- 18833468
TI  - Phytoplankton community and physical-chemical characteristics of water in the
      public reservoir of Cruzeta, RN, Brazil.
AB  - The Phytoplankton community and the abiotic factors of the Cruzeta reservoir were
      studied at three depths, surface, middle (2 m) and bottom, from September, 2004
      to June, 2005, in order to characterize the environment and assess the possible
      factors that influence the compositional change of phytoplankton. Ninety species
      belonging to 6 classes (Chlorophyceae, Bacillariophyceae, Cyanophyceae,
      Dinophyceae, Chrysophyceae and Euglenophyceae) were identified with 66 and 80
      taxonomic units in the dry and rainy season. The most representative class in
      terms of species richness was Chlorophyceae and dominated by Scendesmus
      quadricauda, Oocystis sp. and Chlorella sp. The group cyanobacteria were
      represented by 18 species of diverse morphological characteristics and the
      dominance of Cylindrospermopsis raciborskii in September 2004. The other major
      group, Bacillariophyceae is represented by 21 species with the predominance of
      Aulacoseira granulata in mid-column and bottom waters. The other dominant species
      was Phacus acuminatus of Euglenophyceae. The species diversity and evenness
      indices were high, moderate and low in relation to the three hydroperiod
      registered during the 2004-2005 annual cycle. The reservoir exhibits high
      electrical conductivity (290-550 microS x cm-1), alkaline pH (7.3-9.4), mean
      temperature of 28 degrees C, varying concentrations of dissolved oxygen (3.29-7.6
      mg x L-l) and the greatest concentration of nutrients at the bottom
      (orthophosphate, 0.22-0.62 mg x L-1) with the general tendency of oligo
      mesotrophic status during sampling periods. The chlorophyll a fluctuated to a
      minimum of 1.34 microg x L-l at the bottom in April, 2005 and a maximum of 14.3
      microg x L-l in mid-column water in September, 2004. The reservoir is
      characteristically an oligo-mesotrophic environment.

PMID- 18833469
TI  - A year in a Cerrado wet grassland: a non-seasonal island in a seasonal savanna
      environment.
AB  - In some Cerrado regions where the water table is superficial and soils are
      hydromorphic, we may find wet grasslands. We studied temporal changes in some
      community descriptors, such as species density, plant density, basal area, and
      cylindrical volume in a Cerrado wet grassland in four different seasons of the
      year. We also compared the species richness and composition of the wet grassland
      with a hyperseasonal cerrado, and a seasonal cerrado. We found significant
      differences among the seasons only for species density. Chao-Sorensen similarity
      values varied from 0.86 to 0.99 and, in the wet grassland, were not different
      among the seasons. On the contrary, similarity values between the wet grassland
      and hyperseasonal and seasonal cerrados were low. Species richness was lower in
      the wet grassland and higher in the seasonal cerrado. As long as savannas are
      highly dynamic on all temporal and spatial scales, the wet grassland stability,
      at least in a short-term view, introduces an important heterogeneity in regional
      scale. Wet grasslands are also important in the Cerrado domain to increase b
      diversity, since they are floristically dissimilar with cerrado vegetation.

PMID- 18833470
TI  - Characterization of habitats based on algal periphyton biomass in the upper
      Parana River floodplain, Brazil.
AB  - Considering the relevant role played by the hydrological regime on the structure
      and functioning of floodplains, this study aims at characterizing different types
      of aquatic environments according to periphyton biomass and evaluating the
      influence of the fluviometric levels of the Parana River and other forcing
      functions upon the periphytic community. Periphyton (chlorophyll a) was analyzed
      in 28 habitats, during the years 2000 and 2001, in high and low water seasons.
      Both years were characterized by lacking the characteristic high water season.
      The Principal Components Analysis revealed two groups. The first component was
      positively associated with hydrometric level, electric conductivity, pH and
      transparency, and negatively with total nitrogen and total phosphorus, dissolved
      organic carbon and turbidity. The second component separated the habitats of
      Parana River in the period of low waters from other environments, mainly for
      hydrometric level and high transparency values. Periphytic biomass of the
      habitats demonstrated that the maintenance of the functional integrity of the
      Upper Parana River floodplain is closely related to its hydrologic cycle.

PMID- 18833471
TI  - Bird mixed-flocks and nuclear species in a tecoma savanna in the Pantanal.
AB  - In bird mixed flocks, a prominent species, the so-called nuclear species,
      improves the cohesion and maintenance of the flocks, while other less conspicuous
      species are assumed as satellite. In this study we described the composition, as
      well as examined the existence of both nuclear and satellite species in mixed
      flocks of a savanna in the Pantanal. The observations were developed using three
      transects during the dry season of 2002. Bird species abundance and respective
      rate of participation in mixed flocks were surveyed by transects, while
      intraspecific sociality, communication, foraging maneuvers of species, and
      responses to predators were sampled by direct observations. These parameters were
      evaluated to distinguish nuclear from satellite species. We observed 41 bird
      mixed flocks, which included from 2 to 17 species of which Suiriri suiriri
      (Vieillot), one of the most abundant species, was present in most flocks, often
      represented by 2-4 individuals, whereas most other species occurred lone or in
      pairs. While foraging by acrobatic maneuvers S. suiriri often gave contact calls,
      as well as earlier giving alarm calls if faced with a risk of predation. In
      addition, S. suiriri always started mixed flocks movements. Conversely, most
      other species were silent and closely inspected the vegetation while foraging.
      Such species always followed S. suiriri and seldom gave contact calls. Hence, the
      conspicuous traits exhibited by S. suiriri, potentially, are exploited by the
      other bird species as cues, which are important references for bird mixed flock
      cohesion in a savanna in the southern Pantanal.

PMID- 18833472
TI  - Patterns of prey selection of Trypoxylon (Trypargilum) lactitarse Saussure
      (Hymenoptera: Crabronidae) in southern Brazil.
AB  - This study was carried out in the Parque Municipal das Araucarias, in the
      municipality of Guarapuava, southern Brazil. A total of 449 T. lactitarse nests
      were collected using trap-nests of different diameters. Fifty three species of
      spiders belonging to 7 families were captured by T. lactitarse. Araneidae was the
      most captured family and has been strongly represented by the genus Eustala.
      Through Bray-Curtis's coefficient and the unweighted pair group method average
      (UPGMA), the spiders species can be divided into 3 groups: the smaller group
      includes the most abundant species (Eustala sp1, Eustala sp2, Acacesia
      villalobosi, Alpaida sp1 and Araneus corporosus), the second group includes
      species with intermediate abundance (Wagneriana iguape, Araneus omnicolor,
      Eustala sp4, Alpaida grayi, Eustala sp3, Larinia t-notata, Mangora sp1 and
      Wagneriana iguape), and the third and largest group includes the least abundant
      species (Aysha gr. brevimana 1, Eustala sp5, Wagneriana eupalaestra, Alpaida
      scriba, Alpaida veniliae, Araneus aff. omnicolor, Araneus sicki, Eustala sp8,
      Mangora sp2, Mangora sp3, Wagneriana juquia, Alpaida sp2, Araneus blumenau,
      Eustala sp6, Eustala sp7 and Ocrepeira galianoae). Of 2,029 identified spiders,
      1,171 were captured in the Araucaria forest, 612 in grassland areas and 246 in
      the swamp. Grassland and swamp areas evidenced greater similarity between them
      than to the Araucaria Forest, regarding presence-absence of spider species in T.
      lactitarse's diet, as well as regarding species abundance in these habitats. The
      juvenile number (56%) was significantly higher than the female (38%) and male
      (6%) percentages.

PMID- 18833473
TI  - Mathematical models for Isoptera (Insecta) mound growth.
AB  - In this research we proposed two mathematical models for Isoptera mound growth
      derived from the Von Bertalanffy growth curve, one appropriated for Nasutitermes
      coxipoensis, and a more general formulation. The mean height and the mean
      diameter of ten small colonies were measured each month for twelve months, from
      April, 1995 to April, 1996. Through these data, the monthly volumes were
      calculated for each of them. Then the growth in height and in volume was
      estimated and the models proposed.

PMID- 18833474
TI  - Seasonality of pathogenic fungi in mites of rubber tree plantations adjacent to
      fragments of Cerrado.
AB  - Fungi are the most frequently observed pathogens of mite populations, helping to
      control them on different crops. Twenty-five samples of leaves were collected
      from rubber tree plantations adjacent to two fragments of Cerrado vegetation.
      Each rubber tree plantation had 25 plants selected for sampling and seven leaves
      from around each tree top were collected up to seven to eight meters above
      ground. Approximately 250 individuals of Calacarus heveae Feres, Phyllocoptruta
      seringueirae Feres, and Tenuipalpus heveae Baker, collected randomly, were
      mounted from each plantation. Hirsutella thompsoni Fisher was observed on all
      three mites and T. heveae was the most infected species. The highest infestation
      levels occurred from November to February (rainy season). In the dry season,
      infestation levels were below 5%. Hirsutella thompsonii has potential to be used
      as mycoacaricide during the rainy season.

PMID- 18833475
TI  - Effects of a fire on a population of treefrogs (Scinax cf. alter, Lutz) in a
      restinga habitat in southern Brazil.
AB  - The area of the Dunas da Joaquina, in Santa Catarina island, contains one of the
      most important remnants of restinga habitat in Santa Catarina State, southern
      Brazil. In December 2003, a fire occurred in a portion of this area, affecting
      most of the vegetation, including the bromeliad community. In this study, the
      density of individuals and the diet composition of the bromelicolous treefrog
      Scinax cf. alter were compared between the area affected by the fire and an
      adjacent unburned area. One-hundred-and-fifty-eight ground bromeliads (Vriesea
      friburguensis) were dissected and searched for the presence of treefrogs among
      their leaves. We found 30 frogs in 29.5% (23/78) of the bromeliads from the
      unburned site, with a mean of 1.3 frogs per rosette, and 15 frogs in 12.5%
      (10/80) of the bromeliads from the burned site, with a mean of 1.6 frogs per
      rosette. Eight (27%) of the frogs from the unburned site and eleven (73%) of
      those from the burned site had empty stomachs. Frogs from the burned site also
      contained less prey per stomach than those from the unburned site. The data
      suggest that the fire has negatively affected the local population of Scinax cf.
      alter, though it is possible that the population can recover.

PMID- 18833476
TI  - Cetacean diversity on the Parnaiba Delta, Maranhao state, northeastern Brazil.
AB  - The increase in the research of cetacean surveys on the Brazilian coast has
      brought new data on the distribution of species never reported before. The
      present work reviews the current knowledge on cetaceans species and extends this
      knowledge with an analysis of cetaceans stranded in the Parnaiba Delta, on the
      coast of Maranhao State, Brazil. The studies on cetacean diversity on the coast
      of the Parnaiba Delta were made from August 2004 to August 2006. Fourteen
      strandings were reported, representing six distinct species, such as the
      estuarine dolphin (Sotalia guianensis), humpback whale (Megaptera novaeangliae),
      Bryde's whales (Balaenoptera edeni), dwarf minke whale (Balaenoptera
      acutorostrata), pigmy killer whale (Feresa attenuata), sperm whale (Physeter
      macrocephalus) and two specimens which have not yet been identified. The
      significant degree of cetacean diversity in the region shows that the Parnaiba
      Delta is, possibly, of an important area for cetacean studies in Brasil.

PMID- 18833477
TI  - Can we predict dispersal guilds based on the leaf-height-seed scheme in a
      disjunct cerrado woodland?
AB  - Although there have been advances in methods for extracting information about
      dispersal processes, it is still very difficult to measure them. Predicting
      dispersal groups using single readily-measured traits would facilitate the
      emergence of instructive comparisons among ecological strategies of plants and
      offer a path towards improved synthesis across field experiments. The leaf-height
      seed scheme consists of three functional traits: specific leaf area, plant canopy
      height, and seed mass. We tested, applying logistic regression analysis, whether
      these traits are potential predictors of dispersal guilds in a disjoint cerrado
      woodland site in southeastern Brazil. According to our results, none of the plant
      traits studied could predict dispersal guild; this means that abiotically and
      biotically dispersed species showed similar values of specific leaf area, height,
      and seed mass. The species of both guilds exhibited sclerophylly, probably a
      result of the typical soil nutrient deficiency of cerrado, which also may have
      placed constraints upon plant canopy height regardless of the dispersal mode. In
      the cerrado, some abiotically dispersed trees might present higher than expected
      seed mass as support to the investment in high root-to-shoot ratio at the
      seedling stage. Seeds of bird-dispersed species are limited in size and mass
      because of the small size of most frugivorous birds. Since soil nutrient quality
      might contribute to the similarity between the dispersal guilds regarding the
      three traits of the scheme, other plant traits (e.g., root depth distribution and
      nutrient uptake strategy) that detail the former should be considered in future
      predictive studies.

PMID- 18833478
TI  - Expression of cell adhesion molecules in the normal and T3 blocked development of
      the tadpole's kidney of Bufo arenarum (Amphibian, Anuran, Bufonidae).
AB  - Cell adhesion molecules act as signal transducers from the extracellular
      environment to the cytoskeleton and the nucleus and consequently induce changes
      in the expression pattern of structural proteins. In this study, we showed the
      effect of thyroid hormone (TH) inhibition and arrest of metamorphosis on the
      expression of E-cadherin, beta-and alpha-catenin in the developing kidney of Bufo
      arenarum. Cell adhesion molecules have selective temporal and spatial expression
      during development suggesting a specific role in nephrogenesis. In order to study
      mechanisms controlling the expression of adhesion molecules during renal
      development, we blocked the B. arenarum metamorphosis with a goitrogenic
      substance that blocks TH synthesis. E-cadherin expression in the proximal tubules
      is independent of thyroid control. However, the blockage of TH synthesis causes
      up-regulation of E-cadherin in the collecting ducts, the distal tubules and the
      glomeruli. The expression of beta-and alpha-catenin in the collecting ducts, the
      distal tubules, the glomeruli and the mesonephric mesenchyme is independent of
      TH. TH blockage causes up-regulation of beta-and alpha-catenin in the proximal
      tubules. In contrast to E-cadherin, the expression of the desmosomal cadherin
      desmoglein 1 (Dsg-1) is absent in the control of the larvae kidney during
      metamorphosis and is expressed in some interstitial cells in the KClO4 treated
      larvae. According to this work, the Dsg-1 expression is down-regulated by TH. We
      demonstrated that the expression of E-cadherin, Dsg-1, beta-catenin and alpha
      catenin are differentially affected by TH levels, suggesting a hormone-dependent
      role of these proteins in the B. arenarum renal metamorphosis.

PMID- 18833479
TI  - Ion fluxes and hematological parameters of two teleosts from the Rio Negro,
      Amazon, exposed to hypoxia.
AB  - The aim of this study was to describe the effect of hypoxia on whole body ion
      fluxes and hematological parameters in two Amazonian teleosts: Serrasalmus
      eigenmanni and Metynnis hypsauchen. The increase of Na+ and Cl- effluxes on M.
      hypsauchen exposed to hypoxia may be related to an increase of gill ventilation
      and effective respiratory surface area, to avoid a reduction in the oxygen
      uptake, and/or with the decrease of pHe, that could inhibit Na+ and Cl-
      transporters and, therefore, reduce influx of these ions. Effluxes of Na+ and Cl-
      were lower in hypoxia than in normoxia for S. eigenmanni, possibly because in
      hypoxia this species would reduce gill ventilation and oxygen uptake, which would
      lead to a decrease of gill ion efflux and, consequently, reducing ion loss. The
      increase on hematocrit (Ht) during hypoxia in M. hypsauchen probably was caused
      by an increase of the red blood cell volume (MCV). For S. eigenmanni the increase
      on glucose possibly results from the usage of glucose reserve mobilization.
      Metynnis hypsauchen showed to be more sensitive to hypoxia than Serrasalmus
      eigenmanni, since the first presented more significant alterations on these
      osmoregulatory and hematological parameters. Nevertheless, the alterations
      observed for both species are strategies adopted by fishes to preserve oxygen
      supply to metabolizing tissues during exposure to hypoxia.

PMID- 18833480
TI  - Filamentous fungi isolated from sand and water of "Bairro Novo" and "Casa Caiada"
      beaches, Olinda, Pernambuco, Brazil.
AB  - Fungi comprehend a heterogeneous group of heterotrophic microorganisms that act
      as saprobes or parasites or, less frequently, as symbionts living in association
      with other organisms. They are cosmopolitan and important components of
      ecosystems. Considering the small number of Brazilian papers on the filamentous
      mycota in marine environments, and the need to improve knowledge of the diversity
      of these microfungi in "Casa Caiada" and "Bairro Novo" beaches, Olinda, PE, the
      aim of this work was to isolate and identify the fungi from sand and water
      samples of these ecosystems. Thirty two samplings of sand (surface and 20 cm
      deep) and water (surface and 1 m deep) were carried out during the dry and rainy
      seasons, in low and high tide. From each sand sample, a suspension was made with
      50 g of sand diluted in 90 mL of sterilized distilled water. From each sand
      suspension and water sample, 0.5 mL was spread, in triplicate, onto Petri dishes
      containing Sabouraud Agar added of chloramphenicol. The plates were incubated at
      28 degrees C (+/-2 degrees C). Fifty seven species were isolated, identified, and
      classified in 20 genera. Aspergillus and Penicillium were the most frequent
      genera in both sand and water, with a total of 11 and 19 species, respectively.

PMID- 18833481
TI  - The brain of the common vampire bat, Desmodus rotundus murinus (Wagner, 1840): a
      cytoarchitectural atlas.
AB  - The vampire bat, Desmodus rotundus, is exceptionally agile and stealthy in
      nature. Feeding at night on cattle blood, it is a known scourge carrying rabies.
      It is endowed with a very high neocortical volume among bats, acute olfactory
      capabilities and an accessory olfactory system. These characteristics have
      resulted into an impressive number of neuroanatomical investigations except a
      long due atlas on its brain. This study presents a cytoarchitectural atlas of the
      brain of the common vampire, Desmodus rotundus murinus, in the frontal plane,
      serially between the olfactory bulb and the medulla oblongata. Twenty six
      selected sections are presented, each separated by about 300 to 560 microns. The
      atlas figures show lugol fast blue-cresyl echt violet stained hemisections with
      their matching half in a labeled line drawing. About 595 discrete brain
      structures (some repeating) have been identified. This study is likely to provide
      the accurate localization of nuclear groups, whole structures, fiber tracts, and
      interconnections to facilitate future neuroanatomical and neurophysiological
      investigations on the vampire brain.

PMID- 18833482
TI  - Snakes from the Atlantic Rainforest area of Serra do Mendanha, in Rio de Janeiro
      state, southeastern Brazil: a first approximation to the taxocenosis composition.
AB  - We studied the species composition of the snake community of Serra do Mendanha,
      in Rio de Janeiro state, Southeastern Brazil, with an effort of 800 hours/man in
      different habitats, including undisturbed forest, secondary forest, areas under
      regeneration, and banana plantation. We sampled snakes monthly in the area using
      a combination of methods including intensive visual searching and pitfall traps
      with drift-fences. We found a total of 191 individuals of 27 snake species,
      belonging to four families: Boidae, Colubridae, Elapidae and Viperidae. In terms
      of species richness, the most speciose snake family in the area was Colubridae
      (85.2%; n = 23), followed by Viperidae (7.4%; n = 2), Boidae (3.7%; n = 1) and
      Elapidae (3.7%; n = 1) (Table 1). Quantitatively, the family Colubridae
      represented 81.7% (n = 156) of the total of individuals captured throughout the
      study, followed by Elapidae (13.1% of the individuals; n = 25), Viperidae (4.7%;
      n = 9) and Boidae (0.5%; n = 1). The data obtained in the study allowed a first
      approximation of the richness and composition of the snake fauna from Serra do
      Mendanha, including the records obtained during fieldwork in the present study
      and those of specimens deposited in Institutional Collections and detailed field
      data for each voucher specimen. All records are novel data for the area.

PMID- 18833483
TI  - Pentastomids infecting an invader lizard, Hemidactylus mabouia (Gekkonidae) in
      northeastern Brazil.
AB  - From January to April 2006, 37 specimens of Hemidactylus mabouia were collected
      in houses, in the municipality of Barbalha (7 degrees 20' S and 39 degrees 18'
      W), Ceara State, Northeast Brazil. Among the individuals captured, 17 were
      infected with pentastomids, totalling a prevalence of 45.9%, which did not differ
      between sexes. Host size did not influence the infection intensity. Two species
      of pentastomids were found: Raillietiella frenatus and R. mottae. The prevalence
      of R. frenatus (43.2%) was higher than R. mottae (2.7%), whereas the infection
      intensity of R. frenatus was comparatively lower (1.8 +/- 1.4) than R. mottae (36
      parasites in a single host). Overall mean intensity of infection was 3.8 +/- 8.4
      pentastomids. We found no pentastomid infecting juvenile geckos. The parameters
      of infection in this host population are in accordance to the findings of other
      studies, in which the high parasitism rate was associated to the feeding habits
      of geckos living in houses and buildings. Hemidactylus mabouia is a new host to
      R. mottae and the infection by R. frenatus is the first record of the occurrence
      this pentastomid species in Brazil.

PMID- 18833484
TI  - Individual growth of Heleobia piscium in natural populations (Gastropoda:
      Cochliopidae) from the multiple use natural Reserve Isla Martin Garcia, Buenos
      Aires, Argentina.
AB  - The present work analyses the individual growth of Heleobia piscium in natural
      conditions in coastal drainage channels of the Multiple Use Natural Reserve Isla
      Martin Garcia, Buenos Aires, Argentina. Isla Martin Garcia is located in the
      Upper Rio de la Plata, to the south of the mouth of the Uruguay river (34 degrees
      11' 25" S and 58 degrees 15' 38" W). Monthly collections were made from July 2005
      to July 2006 in the eastern part of the island (Arena Beach). The population of
      H. piscium showed a complex and dynamic structure of sizes during a long period
      of the annual cycle. Two cohorts could be detected. The Bertalanffy growth
      equation was: Lt = 6 (1-e -1.85 (t+0.38)) and Lt = 3.9 (1-e -0.19 (t+4.84)) for
      cohorts 1 and 2, respectively. The pattern of population growth displayed a
      staggered model, where the greatest growth is observed during the summer. The
      reproductive period occurred during six months, from the beginning of summer to
      middle of fall. Based on only one reproductive effort, this pattern is not
      similar to that of other cogeneric species already studied.

PMID- 18833485
TI  - Size and shape variability in the skull of Myotis nigricans (Schinz, 1821)
      (Chiroptera: Vespertilionidae) from two geographic areas in Brazil.
AB  - We present a quantitative analysis of sexual dimorphism and geographic variation
      in the skull of Myotis nigricans (Schinz, 1821) assessed by geometric
      morphometrics. Differences in size and shape of skulls were investigated using 30
      landmarks plotted on two-dimensional images of lateral and ventral views. Results
      of geometric morphometrics revealed sexual dimorphism in the centroid size of the
      skull in both views. Females were larger than males. Nevertheless, there was no
      sexual dimorphism in skull shape of M. nigricans. Geographic variation was
      detected in size and shape of the skull. South Brazilian specimens were
      significantly larger than Ceara specimens only in the lateral view. Differences
      in skull shape were statistically significant in both views: specimens from South
      Brazil were brevirostri and presented a more expanded skull in the posterior
      region while Ceara specimens were longirostri and do not present any expansion in
      the brain case. Ecological factors for these phenomena are discussed in the text.

PMID- 18833486
TI  - Chemosystematics of the rosiflorae.
AB  - The superorder Rosiflorae (sensu Dahlgren, 1980) belongs to the Angiospermae. It
      comprises twelve orders and thirty-eight families formed of species with varied
      habits widely distributed in temperate regions. The chemistry of Rosiflorae
      species is highly diversified; nevertheless it shows clearly phylogenetic
      affinity among the orders, except for Buxales. Flavonoids and triterpenoids are
      the real taxonomic markers for the superorder, due not only to the great number
      of occurrences, but also to the high structural diversity. On the other hand, the
      alkaloids are suitable as chemical markers only for the order Buxales. For orders
      and families of Rosiflorae, analysis of correlations among chemical parameters
      based on flavonoids and triterpenoids, with themselves and with the morphological
      and chemo-morphological parameters, showed evolutionary gradients among these
      taxa in which Trochodendrales occupy a primitive position while Saxifragales have
      the outpost. According to the types of flavonoids found in the superorder, there
      is clearly a higher incidence of flavonols than flavones, suggesting a primitive
      status of the Rosiflorae. Evolutionary advancement parameters relative to
      flavonoid hydroxyl protection show preferential protection mechanisms of
      glycosylation against methylation as well as a high percentage of free hydroxyl
      groups. The order Buxales has an isolated position in the superorder Rosiflorae
      with a high alkaloid production, which is quite exclusive to this taxon.

PMID- 18833487
TI  - Influence of a 60 Hz, 3 microT, electromagnetic field on the somatic maturation
      of wistar rat offspring fed a regional basic diet during pregnancy.
AB  - The aim of the present study was to observe how the exposition of pregnant rats
      to an electromagnetic field (EMF), with frequency of 60 Hz, and a magnetic field
      of 3 microT for 2 hours per day and/or using the so-called Regional Basic Diet
      (RBD), influenced the somatic maturation in their offspring. Four groups were
      formed: Group A (casein), B (casein and EMF), C (RBD) and D (RBD and EMF). The
      diet manipulation occurred during pregnancy. The somatic maturation indexes-
      assessed daily between 12:00 AM and 2:00 PM--were: Eye Opening (EO), Auricle
      Opening (AO), Auditory Canal Opening (ACO), Low Incisor Eruption (LIE), and Upper
      Incisor Eruption (UIE). The association between EMF and deficient diet caused a
      delay in all Somatic Maturation Indexes (SMI) and the RBD caused delay only in
      the AO. Furthermore, the EMF caused delay in AO, ACO, LIE. In relation to the
      body weight, the EMF associated with the deficient diet caused change in the
      twenty-first day of life. The RBD, during pregnancy, caused lower body weight in
      the offspring in the first and third day of life. The body weight of the
      offspring whose mothers were fed casein and exposed to the EMF during pregnancy
      was lower in the third and sixth day of life. In conclusion, the EMF associated
      with under-nutrition caused delay in all SMI. In relation to the body weight, the
      EMF associated with under-nutrition caused a decrease in the body weight at the
      sixth day of life.

PMID- 18833488
TI  - Bipedal locomotion in Tropidurus torquatus (Wied, 1820) and Liolaemus lutzae
      Mertens, 1938.
AB  - Bipedalism has evolved on numerous occasions in phylogenetically diverse lizard
      families. In this paper we describe, for the first time, bipedal locomotion on
      South American lizards, the sand-dweller Liolaemus lutzae and the generalist
      Tropidurus torquatus. The lizards were videotaped running on a racetrack and the
      sequences were analyzed frame by frame. The body posture, as a whole, diverged a
      lot during bipedal locomotion between the two species, even though there was no
      difference regarding their sprint performance. The locomotor behavior of L.
      lutzae is, in general, more similar to the one observed on other sand-dweller
      lizards. Certain particularities are common, such as the digitigrade posture at
      footfall and throughout stance, trunk angles; and tail posture. In contrast, T.
      torquatus exhibited high trunk angles and dragged its tail, in a posture compared
      to basilisks. This body posture could be related to certain characteristics and
      obstacles of a microhabitat such as the one around lakes and streams (basilisks)
      and the one with compact shrubby vegetation (T. torquatus).

PMID- 18833489
TI  - Haematological changes in Nile tilapia experimentally infected with Enterococcus
      sp.
AB  - This study evaluated the haematological changes in Nile tilapia experimentally
      infected with 1 x 10(3) and 1 x 10(6) colony-forming units (CFU)/mL of
      Enterococcus sp. in the swim bladder. The experiment consisted of four treatments
      in triplicates: non-injected fish (NI); fish injected with 1 mL of sterile saline
      solution 0.65% (SAL); fish injected with 1 x 10(3) and 1 x 10(6) CFU/mL of
      Enterococcus diluted in 1 mL sterile saline. Twenty-four hours after injection,
      the fish were anesthetized and the blood collected. The haematological tests
      included red blood cell (RBC) and white blood cell (WBC) counts, hematocrit,
      number of total thrombocytes, and differential counting of WBC. Fish injected
      with 1 x 10(6) CFU/mL of Enterococcus showed a higher number of thrombocytes than
      the other treatments. White blood cell and lymphocyte numbers increased
      significantly in fish injected with 1 x 10(6) CFU/mL of Enterococcus when
      compared to non-injected control. There was significant increase in the number of
      neutrophils in saline injected fish and reduced number of monocytes after
      injections with 1 x 10(6) CFU/mL of Enterococcus. Hematocrit increased in fish
      injected with 1 x 10(3) and 1 x 10(6) CFU/mL of Enterococcus.

PMID- 18833490
TI  - Immunocytochemical study of gastrintestinal endocrine cells in insectivorous bats
      (Mammalia: Chiroptera).
AB  - The regional distribution and relative frequency of endocrine cells in the
      stomach and intestine of Phyllostomidae: Lonchorhina aurita and Molossidae:
      Molossus molossus bats were studied immunohistochemically. Three types of
      immunoreactive (IR) endocrine cells--to serotonin (5-HT), gastrin (GAS) and
      enteroglucagon (GLUC)--were found in the gastric mucosa and four types of IR
      cells were identified in the intestinal mucosa. This study showed an
      interespecfic difference in the regional distribution and relative frequency of
      endocrine cells in the Chiropteran alimentary tract.

PMID- 18833491
TI  - Feeding and morphological analysis of the digestive tract of four species of fish
      (Astyanax altiparanae, Parauchenipterus galeatus, Serrasalmus marginatus and
      Hoplias aff. malabaricus) from the upper Parana River floodplain, Brazil.
AB  - The present study is inspired by the great wealth of species exhibited by the
      ichthiofauna. Not only concepts and techniques of ecology deserve attention, but
      also knowledge in other biological areas, such as zoology and anatomy, are
      necessary. The intention of the present work is to discover the morphology of
      fish through the study of the digestive tract morphology, associating it to diet
      data, in order to better understand the biology of four fish species of the upper
      Parana River floodplain. The samples were collected quarterly in the year 2000
      with gillnets of different meshes. The stomach content was analyzed under a
      stereoscopic microscope and the frequencies of occurrence (FO) and volumetric
      (FV) and the alimentary index (IAi) were calculated. Various morphologic
      characteristics were analyzed and schematized using a light chamber. The species
      were grouped into two trophic guilds - insectivores (Astyanax altiparanae and
      Parauchenipterus galeatus) and piscivores (Serrasalmus marginatus and Hoplias
      aff. malabaricus). The first two, although consumers of insects, preyed on
      different alimentary groups, notably Hymenoptera in the case of A. altiparanae
      and Coleoptera in the case of P. galeatus. Serrasalmus marginatus and H. aff.
      malabaricus consumed mainly fishes. However, only pieces of prey were usually
      found in the stomach content of the first species, whereas whole fishes were
      found in the stomach content of the second. Astyanax altiparanae exhibited
      characteristics that allowed it to obtain food in several compartments of the
      water column. Similarly P. galeatus consumed food resources that were available
      in all aquatic compartments, although the abilities to capture, to manipulate and
      to absorb food differed, as shown by the importance of teeth plates and
      pharyngeal teeth. Serrasalmus marginatus and H. aff. malabaricus, although
      resembling each other in many aspects of the digestive tract morphology, differed
      in the strategies used to capture prey. The analysis showed that, according to
      the main food item of the diet, the species were grouped into two trophic guilds.
      However, those within the same category used different feeding methods, and
      similarity in items consumed does not imply the same group of morphological
      characteristics.

PMID- 18833492
TI  - Morphological abnormalities in Cladocera (Branchiopoda) in a cascade of
      reservoirs in the middle and lower Tiete river (Sao Paulo, Brazil).

PMID- 18833493
TI  - Rectification of description of Notodiaptomus spinuliferus, Dussart and Matsumura
      Tundisi, 1986.

PMID- 18833494
TI  - Gender analysis of papers published in ACTAS ESPANOLAS DE PSIQUIATRIA (1999
      2006).
AB  - INTRODUCTION: The governments and organizations responsible for scientific
      policies try to encourage equality of gender, among their priorities that of
      obtaining equal participation and full integration of women in all aspects of the
      scientific profession. The study analyzes the scientific production of women in
      the areas of Psychiatry by means of the bibliometric study of the papers
      published in ACTAS ESPANOLAS DE PSIQUIATRIA. METHOD: A total of 458 papers
      published from 1999- 2006 period were downloaded from the Science Citation Index
      Expanded database, these including original research papers, review articles and
      clinical cases. A bibliometric study broken down by gender was carried out to
      determine the existence or inequalities between men and women regarding
      scientific productivity, type of document, order of author signatures, on the
      institutional and geographical level. RESULTS: The papers were published by 1,194
      different authors. The gender of 977 authors was identified, 587 (60.08%) men and
      390 (39.92%) women. The percentage of women authorship has risen from 29.92% in
      1999 to 38.86% in 2006. A total of 42.92% of authors having one published article
      were women, while <<the multiple article producing women>> (those with more than
      nine articles) only accounted for 33%. CONCLUSION: Bibliometric studies on
      scientific activity provide essential information to promote gender equality. An
      annual increase over 1% in the number of female authors in the journal has been
      observed, which if it continues will lead to a parity in coming years.

PMID- 18833495
TI  - Psychometric properties of the Spanish validation of the Insight Scale.
AB  - INTRODUCTION: The aim of our study was to validate the Spanish version of the
      Insight Scale (IS) (Birchwood et al., 1994), a multidimensional self-report
      insight scale. METHOD: Observational study in a sample of patients with
      psychosis. A translation-backtranslation of the original scale was elaborated.
      Feasibility was calculated. Concurrent criteria validity with item 12 of PANSS,
      construct convergent and divergent validity with DAI and BPRS were calculated. IS
      scores between voluntary and involuntary inpatients were used for discriminant
      validity. Factor analysis, temporal reliability and internal consistency were
      also examinated. RESULTS: The sample consisted of 61 patients. Interclass
      Correlation Coeficient (ICC) between item 12 of PANSS and IS was 0.49.
      Correlation between IS and DAI, and IS and BPRS was 0.414 (p=0.01) and -0.14
      respectively. Difference between mean IS scores of voluntary (8.37) and
      involuntary inpatients (6.21) was signific (U test Mann-Whitney: 244.5; p=0.005).
      Three factors were extracted that accounted for 68.32% of variance. Cronbach
      alpha was 0,717. CONCLUSIONS: The Spanish version of IS is a quick, simple, self
      report and multidimensional instrument of insight with satisfactory psychometric
      properties.

PMID- 18833496
TI  - Contrast-enhanced ultrasound has come of age.

PMID- 18833497
TI  - Comments and illustrations regarding the guidelines and good clinical practice
      recommendations for contrast-enhanced ultrasound (CEUS)--update 2008.
AB  - The recently published EFSUMB guidelines and recommendations provide general
      advice for the use of ultrasound contrast agents to improve the management of
      patients. They are the subject of this pictorial essay, comments and analysis of
      the literature. CEUS has become the most important imaging method for focal liver
      diseases. Its uses are discussed in detail, especially the characterization of
      liver tumors and the monitoring of local treatment. The recommendations also deal
      with the uses of ultrasound contrast agents for the evaluation of the
      microvasculature and macrovasculature of the kidneys, including the
      characterization of focal renal lesions, the detection of lesions and the
      monitoring of local treatment. CEUS and contrast-enhanced endoscopic ultrasound
      can be used to characterize lesions. Ductal adenocarcinoma as the most common
      tumor of the pancreas is typically hypoenhanced compared to the adjacent
      pancreatic tissue in all phases. Neuroendocrine tumors and serous microcystic
      adenoma of the pancreas are characterized by hypervascularization appearing
      typically hyperenhanced during CEUS. This is of importance for a differential
      diagnosis. Vesicoureteric reflux and blunt abdominal trauma are also mentioned.
      Other parts or chapters of the guidelines are described in a separate paper of
      this supplement.

PMID- 18833498
TI  - Contrast-enhanced ultrasonography in patients with colorectal liver metastases
      after chemotherapy.
AB  - PURPOSE: A systematic single-center analysis was performed to evaluate the
      efficacy of contrast-enhanced ultrasonography (CEUS) in the detection of
      colorectal liver metastases in patients with systemic chemotherapy in their
      medical history. MATERIALS AND METHODS: Between May 2005 and December 2007, 48
      patients were referred to our institution for further evaluation after
      chemotherapeutic pretreatment for colorectal liver metastases. In all cases, the
      liver was screened by both unenhanced and contrast-enhanced ultrasonography with
      SonoVue to detect focal liver lesions. The results of sonographic explorations
      were prospectively collected and compared with intraoperative findings including
      histopathological results as reference. RESULTS: A total of 40 patients underwent
      laparotomy and were included in the analysis. The rate of correct ultrasound
      findings (rate of detection) increased from 24 patients (60%) with 35 metastases
      (57.4%) to 31 patients (77.5%) with 50 metastases (82.0%) after administration of
      SonoVue. Thus CEUS showed a significantly improved sensitivity compared to
      unenhanced US in both patient-by-patient analysis (79.5 versus 63.2%, p = 0.041)
      and lesion-by-lesion analysis (82.0 vs. 60.3%, p = 0.0008). On the basis of the
      ultrasound results, the surgical strategy had to be changed in 16 (40.0%) cases
      examined by unenhanced US compared to only nine cases (22.5%) examined by CEUS (p
      = 0.002). In CEUS a higher number of lesions were identified with an increasing
      metastasis size. CONCLUSION: After chemotherapeutic pretreatment, unenhanced US
      should be replaced by CEUS for the detection of liver metastases from colorectal
      carcinoma.

PMID- 18833499
TI  - Diagnostic and prognostic value of contrast-enhanced ultrasound in acute stroke.
AB  - In the last decade transcranial color-coded sonography (TCCS) was established as
      a routine in neurovascular departments for the evaluation of brain-supplying
      vessels in cerebrovascular diseases. TCCS has demonstrated feasibility and
      validity for the evaluation of the basal cerebral arteries, especially for the
      middle cerebral artery (MCA). In some patients an insufficient bone window may
      limit the diagnostic power. The application of microbubble agents can overcome
      this limitation in most patients. Beside the demonstration of vessel pathology
      such as stenosis and occlusion, TCCS also provides prognostic information. In the
      case of proximal MCA occlusion shown by TCCS within 6 hours of stroke, nearly 90
      % of the patients suffered an unfavorable outcome. Furthermore TCCS is suitable
      for monitoring thrombolysis in acute stroke to detect whether there is
      recanalization of the affected vessel. The possibility for bedside examination,
      the non-invasiveness and the cost-effectiveness are features which make TCCS an
      optimal tool for the evaluation of cerebral vessels in acute ischemic stroke.

PMID- 18833501
TI  - [Addiction: challenges in diagnosis and therapy by comorbidity].

PMID- 18833502
TI  - [Theory of mind in schizophrenia: clinical aspects and empirical research].
AB  - The term Theory of Mind (ToM) refers to the capacity to infer one's own and other
      persons' mental states. A substantial body of research has highlighted impaired
      ToM in a variety of neuropsychiatric disorders, including schizophrenia. There is
      good empirical evidence that ToM is specifically impaired in schizophrenia and
      that many psychotic symptoms--for instance, delusions of alien control and
      persecution--may best be understood in light of a disturbed capacity in patients
      to relate their own intentions to executing behavior, and to monitor others'
      intentions. However, it is still under debate if impaired ToM in schizophrenia is
      a state- or trait marker and whether patients could benefit from cognitive
      training in this domain. Recently, research has not only emphasized social
      cognitive deficits in patients, but has also focussed on interactions between ToM
      with language and other cognitive functions. Furthermore, interest in
      subprocesses of social cognition in psychotic spectrum disorders (e. g.
      schizotypy) is growing. The aim of this article is to line out clinical aspects
      of disturbed social cognition, to clarify terms used in this context as well as
      to present the latest research approaches into social cognition deficits.

PMID- 18833503
TI  - [Psychometric evaluation of a neuropsychological test battery measuring cognitive
      dysfunction in cancer patients--recommendations for a screening tool].
AB  - Cognitive dysfunctions in cancer patients as a consequence of various oncologic
      treatments (e. g. chemotherapy) have been increasingly described within the
      current literature. As most of the neuropsychological tests used within those
      studies have been developed and validated in neurologic or psychiatric patient
      populations, it remained unclear whether the application of such measures would
      be appropriate in cancer patients as well. The present study focused on the
      psychometric evaluation of a neuropsychological test battery that had been used
      in two empirical studies carried out at the Department of Medical Psychology,
      University Medical Center Hamburg-Eppendorf. In addition, recommendations for a
      basic screening tool were developed. Both study samples were analyzed separately.
      One sample included breast cancer patients an average of five years following
      treatment; the second sample included patients with hematological malignancies
      which had been tested before and 100 days after stem cell transplantation. A
      further data set of a mixed cancer population (breast cancer patients and
      patients with hematological malignancies) and corresponding neuropsychological
      measures could be used for the replication of our results. Those patients had
      been investigated during an intervention study while receiving rehabilitation at
      the Clinic for Tumor Biology in Freiburg. Results show that primarily measures
      for attention were found to have satisfying to high reliability and contribute
      independently to the explanation of variance of neuropsychological dysfunctions
      after cancer treatment. In particular, the subtest "Alertness" of the Test
      Battery for Attentional Performance (TAP) can be recommended as a basic screening
      for the assessment of cognitive dysfunctions in breast cancer patients and
      patients with hematological malignancies.

PMID- 18833504
TI  - [Rasagiline in daily clinical use. Results of a treatment study of Parkinson
      patients with a combination treatment].
AB  - Rasagiline (Azilect) is a potent, highly selective and irreversible inhibitor of
      monoamine oxidase type B of the second generation. Rasagiline is indicated for
      the treatment of Parkinson's disease (PD) as monotherapy (without levodopa) or as
      adjunct therapy (with levodopa) in patients with end of dose fluctuations. The
      efficacy and tolerability of rasagiline has been demonstrated in large-scale,
      controlled clinical studies in patients with early PD as well as with more
      advanced PD. This multicentred post-marketing observational study included an
      investigation of the efficacy and tolerability of rasagiline in a large patient
      population under conditions of the daily routine in neurologic practice with a
      special attention on the collection of data regarding a patients' subjective
      evaluation of quality of life. A total of 754 patients with Parkinson's disease
      were enrolled, 545 of the patients (63% male patients, mean age 68 years, mean
      duration of PD 6 years, Hoehn & Yahr stage II to III in 69% of the patients)
      started rasagiline 1 mg/day as adjunct therapy for up to 4 months. The PD
      symptoms were rated by the physicians using the Columbia University Rating Scale
      (CURS) and the clinical fluctuations subscale of the Unified Parkinson's Disease
      Rating Scale (UPDRS, part IV B). Different aspects of quality of life were rated
      by the patients using the self-rating Parkinson's Disease Questionaire (PDQ-39).
      In addition, patients documented the number of hours spend in the OFF-state in
      "24-hour" home diaries prior to each of the assessment visits. During the
      treatment period rasagiline was most frequently co-administered with levodopa/DCI
      (81.7%) and/or dopamine agonists (65.8%). The mean treatment duration was 117.4
      (+/-36.4) days, during which PD medication remained unchanged in 86.6% of the
      cases. The improvement rates in each of the CURS items ranged between 31.1% to
      48.4% and the total score was reduced by 22% under the therapy of rasagiline. In
      the motor part (tremor, rigidity, bradykinesia) the total score was reduced from
      6.2 to 4.8, within the other items from 14.7 to 11.5. The proportion of patients
      without OFF-periods increased from 33.3% to 49.5%. Determined from "24-hours"
      home diaries, time spend in the OFF-state during wake time decreased from 120
      minutes to 45 minutes. In all 8 aspects of quality of life rated by the patients
      an reduction of the disability could be documented. The PDQ-39 total score was
      reduced from 36.4 by 7.3 points (20.1%). In total, 29 of the 545 patients who
      received rasagiline as combination therapy had switched directly from previous
      combination therapy with selegiline. In this subgroup CURS total score improved
      from 17.0 to 12.9 points during treatment. The proportion of patients without OFF
      periods increased from 36% to 48% and the daily time spent in the OFF-state was
      reduced from 45 minutes to 30 minutes. The PDQ-39 total score improved by 6.5
      points (22.2%). All in all, adverse events were reported by 8.4% of the patients.
      In conclusion this post-marketing observational study has shown that in patients
      with pre-existing combination therapy the add-on medication of rasagiline
      resulted in improvements of motor and non-motor functions. Furthermore, motor
      complications were significantly reduced and led to an improved quality of life
      in the self-estimation of the patients. This also applies to those patients with
      selegiline pre-treatment.

PMID- 18833505
TI  - [Personality disorders in a clinical sample of Cannabis dependent young adults].
AB  - INTRODUCTION: Cannabis addiction with comorbid personality disorders (PDs) is
      associated with a heavier individual burden of disease. Most previous studies
      focussed on singular disorders like borderline or antisocial PD, there is little
      data available on the full range of PD. Even less is known about the prevalence
      of PD with cannabis addiction in inpatient settings. The aim of this study is to
      investigate the frequency of PD and their relevance in treatment of young adult
      Cannabis-dependent inpatients. METHODS: 99 adolescents and young adults diagnosed
      with Cannabis dependence according to DSM I, were investigated during their
      detoxification treatment in an addiction treatment ward. Personality disorders
      were assessed using the SCID II questionnaire. RESULTS: The intensity of
      personality disorder traits was high in this inpatient sample. The probands
      showed a higher burden of disease from PDs other than the antisocial and
      Borderline PDs previously reported. Almost 90% of the subjects received the
      diagnosis of an antisocial PD, more than half had a paranoid and more than a
      third suffers from a Borderline PD. More than 35% of the sample had more than
      three PDs. There were no consistent relationships between PDs and concurrent
      consumption of other drugs, severity of drug addiction or delinquency.
      CONCLUSION: There is evidence of PDs in almost all inpatient Cannabis-dependent
      adolescents and young adults. Diagnosis and treatment of these subjects has to
      provide not only addiction-specific approaches but also strategies to improve
      dysfunctional behaviour caused by personality disorder characteristics.

PMID- 18833506
TI  - [Familial Alzheimer's disease with presenilin 2 N141I mutation. A case report].
AB  - Alzheimer's disease (AD) is the most common form of dementia. Approximately 0.5
      per cent of all AD is caused by single major gene mutations and autosomal
      dominant inheritance. These familial types with early-onset (EOFAD) usually
      display dementia before the age of 60. Such mutations have been found in the gene
      encoding amyloid precursor protein (APP), and in the genes encoding presenilin 1
      (PSEN1) or presenilin 2 (PSEN2). We herein report the case of a German patient
      with a EOFAD and a missense mutation at codon 141 (N141I) of the PSEN2 gene. The
      patient came to our psychiatric clinic for the first time when she was 49 years
      old. During the following 3 years, her Mini-Mental-State-Examination (MMSE) score
      dropped from 14 to 0 points. Positron emission tomography with [18F]
      Fluorodeoxyglucose (18F-FDG PET) demonstrated glucose reduction left parietal and
      in the pre-cuneus region. Follow-up 18F-FDG PET studies showed progressive
      hypometabolism of both temporoparietal lobes and left frontal lobe.

PMID- 18833507
TI  - [Hashimoto encephalopathy--a difficult differential diagnosis. A case report of
      reversible dementia and psychosis].
AB  - INTRODUCTION: Hashimoto encephalopathy is a rare disease that is associated with
      Hashimoto thyreoiditis. Dementia, disturbances of consciousness and epileptic
      seizures are the most common features. CASE REPORT: We report a case of Hashimoto
      encephalopathy in a 74-year-old woman who presented with psychotic episodes,
      visual hallucinations, dementia, tremor, rigidity and fluctuation of
      consciousness. After treatment with steroids, cognitive function became normal
      and other symptoms improved significantly. CONCLUSION: Hashimoto encephalopathy
      should be considered as a differential diagnosis of psychosis in combination with
      dementia and other neurological symptoms to dementia with Lewy bodies and
      Creutzfeldt-Jakob disease.

PMID- 18833508
TI  - [Social anxiety disorder--diagnostics and treatment options].

PMID- 18833510
TI  - [Radiological diagnosis of primary CNS lymphoma.]

PMID- 18833509
TI  - "Dry biopsies" with spraying of dilute epinephrine optimize biopsy mapping of
      long segment Barrett's esophagus.
AB  - BACKGROUND AND STUDY AIMS: For surveillance of Barrett's esophagus random
      stepwise four-quadrant biopsy (4QB) is recommended for detecting macroscopically
      occult neoplasias. Thorough performance of the systematic protocol is commonly
      hampered by poor visibility due to oozing from biopsy sites. Topical application
      of dilute epinephrine may prevent bleeding by vasoconstriction of superficial
      microvessels and might therefore enable "dry biopsy" sampling. The aim of this
      study was to examine the safety and efficacy of spraying dilute epinephrine for
      optimal 4QB mapping of Barrett's esophagus. PATIENTS AND METHODS: In this
      prospective, double-blind trial 40 patients with known long segment Barrett's
      esophagus were randomly allocated to undergo spraying with either dilute
      epinephrine (1 : 20 000) (epinephrine group; n = 20) or saline (control group; n
      = 20) before 4QB sampling. During endoscopies patients received continuous
      monitoring of vital parameters. Endoscopists blinded to randomization assessed
      visibility scores during biopsy sampling. Additionally, electronically stored
      images of the Barrett's esophagus segment after 4QB sampling were evaluated by
      blinded assessors. RESULTS: The mean length of Barrett's segments was 5.5 +/- 1.8
      cm and the mean number of 4QBs was 12.5 +/- 3.6 with no statistically significant
      differences between control and epinephrine groups. Epinephrine spraying did not
      affect patients' vital parameters. Visualization ratings by endoscopists on site
      and by the assessors of the stored images were significantly better in the
      epinephrine compared with the control group (P < 0.05). Moreover, epinephrine
      spraying reduced the time for 4QB sampling (P = 0.015) and the mean number of
      saline flushes needed to maintain visibility (P = 0.0003). CONCLUSIONS: The novel
      "dry biopsy" technique with spraying of dilute epinephrine is safe, and
      facilitates thorough performance of systematic 4QB mapping of Barrett's esophagus
      by improvement of visibility.

PMID- 18833511
TI  - [Malignitatsbestimmung von Weichteilsarkomen - Welche Bedeutung haben Grosse und
      Tiefe?]

PMID- 18833513
TI  - [Lungenembolie - Kann auf Kompressionsultraschall verzichtet werden?]

PMID- 18833512
TI  - [Fetale Neuroradiologie - Deutliche Diskrepanzen bei verschiedenen Untersuchern.]

PMID- 18833515
TI  - [Stenose der Arteria carotis interna - Effektive Speckle-Reduktion erhoht die
      Qualitat.]

PMID- 18833514
TI  - [Aneurysma-induzierte Subarachnoidalblutung - Spatfolgen in der MRT.]

PMID- 18833516
TI  - [Systemischer Lupus erythematodes - Neuroimaging deckt neuropsychiatrische
      Beteiligung auf.]

PMID- 18833517
TI  - [Koronare Herzkrankheit - Hohe diagnostische Genauigkeit in der 3-T-MRT.]

PMID- 18833518
TI  - [Brustkrebsdiagnose - Bessere sonografische Malignomvorhersage.]

PMID- 18833519
TI  - [Padiatrische CT - Sedierung mit Propofol - eine Alternative zu Pentobarbital?]

PMID- 18833520
TI  - [CT-Urografie - Verbessern Diuretika die Darstellung des oberen Harntrakts?]

PMID- 18833521
TI  - [Schulterluxationen - Quantifizierung glenoidaler Knochenverluste im CT moglich.]

PMID- 18833522
TI  - [Prof. Dr. Claus D. Claussen, Kongressprasident - Einladung zum 90. Deutschen
      Rontgenkongress 20.-23. Mai 2009 in Berlin.]

PMID- 18833523
TI  - [Wir gratulieren im Oktober.]

PMID- 18833524
TI  - [Verbot von Zuweisermodellen in der Radiologie.]

PMID- 18833525
TI  - Chondrosarcoma of the greater cornu of the hyoid: a case report and literature
      review.
AB  - We report an unusual case of a young woman with chondrosarcoma affecting the
      greater cornu of the hyoid bone. Only a handful of reports of primary
      chondrosarcoma involving the hyoid exist in the world literature. The case
      described presented as a swelling in the submandibular triangle, and as such
      posed a particular clinical and radiologic diagnostic challenge. Our subsequent
      surgical management of this rare entity comprised local excision followed by
      close observation, and is defined in the context of the existing literature. Two
      years after surgery, the patient remained free of tumor recurrence; she was
      subsequently lost to follow-up.

PMID- 18833526
TI  - Otolaryngologists and orbital pseudotumor: a case report.
AB  - Orbital pseudotumor (idiopathic orbital inflammation) is the third most common
      orbital disease, accounting for 5 to 6% of orbital disorders. It often presents
      in a manner very similar to inflammatory or neoplastic sinus disease. In
      addition, sinus disease is often a cause of orbital pseudotumor, although the
      etiology of this entity has yet to be defined. Treatment with steroids is usually
      successful early on, but long-term treatment-failure and recurrence rates are
      high. Despite otolaryngologists' intimate knowledge of sinus pathology, we have
      generally not been heavily involved in researching the causes and treatment of
      orbital pseudotumors. In this article, we report the case of an affected patient
      who presented with an orbital mass on radiography. The mass was likely the result
      of sinus disease in the setting of an untreated orbital floor fracture. We
      describe the clinical, radiographic, and operative features of this case, and we
      discuss the otolaryngologist's role in the management of orbital pseudotumors.

PMID- 18833527
TI  - Laryngopharyngeal reflux: concepts and controversies.

PMID- 18833528
TI  - A case of rhinolithiasis.

PMID- 18833529
TI  - Mucosal tear.

PMID- 18833530
TI  - Transthoracic/transcervical approach to cervicothoracic thyroid cancer.

PMID- 18833531
TI  - Benign paroxysmal positional vertigo and other vestibular symptoms in Meniere
      disease.

PMID- 18833532
TI  - The management of severe upper airway obstruction in the newborn.

PMID- 18833533
TI  - Assessments of the size of tympanic membrane perforations: a comparison of
      clinical estimations with video-otoscopic calculations.
AB  - We conducted a study to determine how accurate various ENT specialists were in
      estimating the size of 100 tympanic membrane (TM) perforations with standard
      otoscopy. The specialists included, in descending order of rank, 2 Consultant
      Surgeons, 2 Senior Registrars, and 2 Registrars, all of whom had confirmed good
      vision. We compared their estimates, which were made independently and expressed
      as a percentage of the total area of the TM, with exact measurements calculated
      with computer-based video-otoscopy. We found that the video-otoscopic
      calculations were far superior to the estimates of the specialists, even the most
      experienced Consultants (p < 0.01). We recommend that video-otoscopy be used
      whenever possible.

PMID- 18833534
TI  - Resveratrol protects auditory hair cells from gentamicin toxicity.
AB  - Resveratrol is a naturally occurring polyphenol that is synthesized by a variety
      of plant species. It is abundant in grapes and grape products (e.g., red wine).
      Resveratrol has demonstrated reactive oxygen species (ROS) scavenger activity,
      and it has been linked to nuclear factor-kappa B (NF-kappaB) activity. We
      recently demonstrated that NF-kappaB is important to the survival of immature
      mammalian hair cells. Therefore, we undertook an in vitro experiment to determine
      if resveratrol is able to exert some protective influence against gentamicin
      induced damage to and death of auditory hair cells. To accomplish this, we
      dissected the organ of Corti (OC) from newborn Sprague-Dawley rats and cultured
      the OCs in medium overnight for recovery. We treated two groups of OC explants
      with different concentrations of resveratrol plus gentamicin for 24 hours; for
      comparison and control purposes, we also treated a group of explants with
      gentamicin only and we left a group untreated. We found that resveratrol in both
      concentrations had a moderate but statistically significant protective effect
      against gentamicin-induced toxicity in vitro.

PMID- 18833535
TI  - An alternative treatment for facial nerve tumors: short-term results of
      radiotherapy.
AB  - A review of medical records of patients undergoing radiotherapy for facial nerve
      tumors was undertaken to determine subsequent facial nerve results, hearing
      results, and tumor control. Two patients with facial nerve tumors received this
      treatment. Facial nerve function remains excellent in one patient and
      significantly improved in the other. Neither tumor demonstrated growth. Current
      philosophies of facial nerve schwannoma management attempt to balance tumor
      control with facial nerve function. Radiotherapy for these tumors appears to
      preserve short-term facial function and may be a viable alternative to surgical
      management.

PMID- 18833536
TI  - Superior turbinate pneumatization in patients with chronic rhinosinusitis:
      prevalence on paranasal sinus CT.
AB  - With the availability of high-resolution computed tomography (CT), a great deal
      of attention has been paid to the anatomy of the paranasal sinuses. But while
      investigators have focused on the osteomeatal complex and its relation to chronic
      rhinosinusitis, there has been little discussion of the superior turbinate.
      Although a few anatomic studies have tried to quantify pneumatization of the
      superior turbinate, the prevalence of this finding on radiography is not well
      addressed in the literature. We prospectively studied 100 consecutively
      presenting patients who underwent coronal CT of the paranasal sinuses (200 sides)
      for the evaluation of symptoms of chronic rhinosinusitis at an academic tertiary
      referral center to determine the prevalence of pneumatization of the superior
      turbinate. We found evidence of pneumatization in 44 of the 200 sides, for a
      prevalence of 22%. In all, pneumatized superior turbinates were found in 27
      patients (27%)-bilaterally in 17 (17%) and unilaterally in 10 (10%).

PMID- 18833537
TI  - Oropharyngeal and laryngeal burn resulting from exposure to endoscope
      disinfectant: a case report.
AB  - Iatrogenic injury from medical disinfectants is an uncommon but potentially
      devastating complication. We report an unusual, but severe, upper aerodigestive
      complication from the use of ortho-Phthalaldehyde solution, a commonly used
      endoscope disinfectant.

PMID- 18833538
TI  - Squamous cell carcinoma of the buccal mucosa: a retrospective analysis of 22
      cases.
AB  - We examined our institution's experience with 22 cases of previously untreated
      buccal squamous cell carcinoma via a retrospective chart review. Eleven of these
      patients had been treated with a combination of surgical excision and
      postoperative radiation therapy, 8 patients with surgical excision alone, and 3
      patients with radiation therapy alone. The overall 3-year locoregional recurrence
      rate was 32% (n = 7). The 3-year survival rates were 82% after surgery plus
      radiation (9 of 11 patients), 63% after surgery alone (5 of 8), and 33% after
      radiation alone (1 of 3). Three-year T-category-specific survival rates were 100%
      for category T1 tumors (3 of 3 patients), 73% for T2 (8 of 11), 50% for T3 (3 of
      6), and 50% for T4 (1 of 2). Although the small size of our study precluded any
      statistically significant conclusions, we believe that locoregional control and
      survival rates may be greater with surgical excision plus postoperative radiation
      than with treatment with either modality alone.

PMID- 18833539
TI  - Angiogenic non-Hodgkin T/natural killer (NK)-cell lymphoma: report of three
      cases.
AB  - Angiogenic T/natural killer (NK)-cell lymphoma is a non-Hodgkin lymphoma
      characterized by necrosis and vascular destruction that is strongly associated
      with Epstein-Barr virus and AIDS. Early diagnosis is essential to improve the
      chances of patient survival, but severe local inflammatory infiltrate impairs
      histologic diagnosis by obscuring neoplastic cells. The most common markers are
      CD2, CD56, cytoplasmic CD3, and CD43 EBV. We describe 3 cases of angiogenic T/NK
      cell lymphoma that show the diverse presentation of the same disease. Patient 1
      was HIV positive and had nasal obstruction, facial edema, and ulceration of the
      nasal mucosa. Patient 2 had fever, a sore throat, and weight loss. Patient 3 had
      facial edema, fever, proptosis, and rapid development of neurologic alterations.
      Several biopsies were needed for histologic confirmation in these patients,
      despite positivity for the CD3 and CD56 markers.

PMID- 18833541
TI  - Canine laparoscopic and laparoscopic-assisted ovariohysterectomy and ovariectomy.
AB  - As the benefits of minimally invasive surgery are more widely recognized by
      veterinarians and their clients, laparoscopic sterilization of female dogs is
      growing in popularity. Laparoscopic ovariohysterectomy and ovariectomy procedures
      in dogs are associated with less postoperative pain and a faster return to normal
      activity versus open sterilization procedures. The advent of newer laparoscopic
      electrocoagulation devices has further increased the technical feasibility and
      popularity of these procedures.

PMID- 18833542
TI  - Diagnosis of urolithiasis.
AB  - Diagnostic imaging is usually required to determine the presence of urolithiasis.
      Double-contrast cystography is more accurate than survey radiography and
      approximately as accurate as ultrasonography. Knowledge of the mineral
      composition of calculi helps direct appropriate management of urolithiasis, and
      signalment can help predict composition with about 70% accuracy. In cats, about
      half of cystic calculi are struvite and half are calcium oxalate; most
      nephroliths and ureteroliths are calcium oxalate. In female dogs, struvite
      uroliths are the predominant type found in the bladder. In male dogs, breed plays
      a strong role in prediction of bladder urolith type. It is difficult to predict
      the composition of nephroliths and ureteroliths based on signalment alone in
      dogs. Urinalysis and imaging findings can help in predicting urolith composition,
      although chemical analysis is necessary for definitive diagnosis.

PMID- 18833543
TI  - Aging diseases--do they prevent preventive health care from saving costs?
AB  - The potential of preventive health-care services to save costs is intensely
      debated. On the one hand, a longer life span increases the probability that new
      and costly diseases occur. On the other hand, a higher life expectancy postpones
      the expensive last year of life (LYOL), which becomes cheaper with age. Using US
      expenditure data on survivors and decedents the paper shows that prevention in
      the general population causes expenditures for additional diseases that are
      larger than the savings from postponing the LYOL. This result may also hold for
      prevention in diseased individuals.

PMID- 18833544
TI  - Efficacy of systemic insecticides on the gall wasp Quadrastichus erythrinae in
      wiliwili trees (Erythrina spp.).
AB  - BACKGROUND: Erythrina gall wasp (EGW), Quadrastichus erythrinae Kim, was first
      found on Oahu Island, Hawaii, in April 2005. Its rapid spread and infestation in
      wiliwili trees (Erythrina spp.) have brought an urgent need to suppress its
      population. Little is known about the control of EGW in wiliwili trees. RESULTS:
      Among the systemic insecticides abamectin, dinotefuran and imidacloprid, applied
      via trunk injections or soil drenches, injections of imidacloprid showed better
      control of EGW in wiliwili trees. All the imidacloprid injection treatments had
      varying levels of effectiveness against EGW, but not the soil drench. The levels
      of imidacloprid were higher in lower canopies than those in the other parts
      within a tree. Imidacloprid remained detectable 1 year after treatment. The trees
      injected with the products IMA-jet and Merit 200 SL via Arborjet had lower
      infestation severity ratings for the entire growth season and carried more
      imidacloprid than those with Imicide via Mauget or Pointer via Wedgle injections.
      CONCLUSION: The results indicate that, among the three insecticides tested,
      imidacloprid is most effective against EGW in the trees. Concentrations of
      imidacloprid in the leaves need to be 4 mg kg(-1) or higher for good EGW control.

PMID- 18833545
TI  - Investigation of metabolite changes in the transition from pre-invasive to
      invasive cervical cancer measured using (1)H and (31)P magic angle spinning MRS
      of intact tissue.
AB  - The aim of this study was to determine the metabolic changes in the transition
      from pre-invasive to invasive cervical cancer using high-resolution magic angle
      spinning (HR-MAS) MRS. Biopsy specimens were obtained from women with
      histologically normal cervix (n = 5), cervical intraepithelial neoplasia (CIN;
      mild, n = 5; moderate/severe, n = 40), and invasive cancer (n = 23). (1)H HR-MAS
      MRS data were acquired using a Bruker Avance 11.74 T spectrometer (Carr-Purcell
      Meiboom-Gill sequence; TR = 4.8 s; TE = 135 ms; 512 scans; 41 min acquisition).
      (31)P HR-MAS spectra were obtained from the normal subjects and cancer patients
      only (as acetic acid applied before tissue sampling in patients with CIN impaired
      spectral quality) using a (1)H-decoupled pulse-acquire sequence (TR = 2.82 s;
      2048 scans; 96 min acquisition). Peak assignments were based on values reported
      in the literature. Peak areas were measured using the AMARES algorithm. Estimated
      metabolite concentrations were compared between patient diagnostic categories and
      tissue histology using independent samples t tests. Comparisons based on patient
      category at diagnosis showed significantly higher estimated concentrations of
      choline (P = 0.0001) and phosphocholine (P = 0.002) in tissue from patients with
      cancer than from patients with high-grade dyskaryosis, but no differences between
      non-cancer groups. Division by histology of the sample also showed increases in
      choline (P = 0.002) and phosphocholine (P = 0.002) in cancer compared with high
      grade CIN tissue. Phosphoethanolamine was increased in cancer compared with
      normal tissue (P = 0.0001). Estimated concentrations of alanine (P = 0.01) and
      creatine (P = 0.008) were significantly reduced in normal tissue from cancer
      patients compared with normal tissue from non-cancer patients. The estimated
      concentration of choline was significantly increased in CIN tissue from cancer
      patients compared with CIN tissue from non-cancer patients (P = 0.0001).
      Estimated concentrations of choline-containing metabolites increased from pre
      invasive to invasive cervical cancer. Concurrent metabolite depletion occurs in
      normal tissue adjacent to cancer tissue.

PMID- 18833546
TI  - Determination of metabolite concentrations in human brain tumour biopsy samples
      using HR-MAS and ERETIC measurements.
AB  - Accurate determination of the concentration of the metabolites contained in
      intact human biopsies of 10 glioblastoma multiforme samples was achieved using
      one-dimensional (1)H high-resolution magic angle spinning (HR-MAS) NMR combined
      with ERETIC (electronic reference to in vivo concentrations) measurements. The
      amount of sample used ranged from 6.8 to 12.9 mg. Metabolite concentrations were
      measured in each sample using two methods: with DSS (2,2-dimethyl-2-silapentane-5
      sulfonate sodium salt) as an internal reference and with ERETIC as an external
      electronically generated reference. The ERETIC signal was shown to be highly
      reproducible and did not affect the spectral quality. The concentrations
      calculated by the ERETIC method in model solutions were shown to be independent
      of the salt concentration in the range typically found in biological samples (0
      250 mM). The ERETIC method proved to be straightforward to use in tissues and
      much more robust than the internal standard method. The concentrations calculated
      using the internal DSS concentration were systematically found to be higher than
      those determined using the ERETIC technique. These results indicate a possible
      interaction of the DSS molecules with the biopsy sample. Moreover, variations in
      the sample preparation process, with possible loss of DSS solution, may hamper
      the quantification process, as happens in one of the ten samples analysed. In
      this study, the ERETIC method was validated on model solutions and used in brain
      tumour tissues. Calculated metabolite concentrations obtained with the ERETIC
      procedure matched the values determined in the same type of tumours by in vivo,
      ex vivo and in vitro methodologies.

PMID- 18833547
TI  - Stereoselective glycal fluorophosphorylation: synthesis of ADP-2-fluoroheptose,
      an inhibitor of the LPS biosynthesis.
AB  - Heptosides are found in important bacterial glycolipids such as
      lipopolysaccharide (LPS), the biosynthesis of which is targeted for the
      development of novel antibacterial agents. This work describes the synthesis of a
      fluorinated analogue of ADP-L-glycero-beta-D-manno-heptopyranose, the donor
      substrate of the heptosyl transferase WaaC, which catalyzes the incorporation of
      this carbohydrate into LPS. Synthetically, the key step for the preparation of
      ADP-2F-heptose is the simultaneous and stereoselective installation of both the
      fluorine atom at C-2 and the phosphoryl group at C-1 through a selectfluor
      mediated (selectfluor=1-chloromethyl-4-fluorodiazoniabicyclo[2.2.2]octane
      bis(triflate)) electrophilic addition/nucleophilic substitution involving a
      heptosylglycal. Therefore, we detail in this article 1) the stereoselective
      preparation of the key intermediates heptosylglycals, 2) the development of a new
      fluorophosphorylation procedure allowing an excellent beta-gluco
      stereoselectivity with "all-equatorial" glycals, 3) the synthesis of the target
      ADP-2F-heptose, and 4) some comments on the contacts observed between the
      fluorine atom of the final molecule and the protein in the crystallographic
      structure of heptosyltransferase WaaC.

PMID- 18833548
TI  - Reaction control in the organocatalytic asymmetric one-pot, three-component
      reaction of aldehydes, diethyl alpha-aminomalonate and nitroalkenes: toward
      diversity-oriented synthesis.

PMID- 18833549
TI  - Molecular basis for beta-glucosidase inhibition by ring-modified calystegine
      analogues.

PMID- 18833550
TI  - Highly sensitive detection of mercury(II) ions by fluorescence polarization
      enhanced by gold nanoparticles.

PMID- 18833551
TI  - Nanostructured TiO2 films templated by amphiphilic dendritic core-double-shell
      macromolecules: from isolated nanorings to continuous 2D mesoporous networks.

PMID- 18833552
TI  - Nanostructure formation enhances the activity of LPS-neutralizing peptides.
AB  - Peptides that interact with lipopolysaccharide (LPS) can provide the basis for
      the development of new antisepsis agents. In this work, several LPS-neutralizing
      acyl peptides derived from LALF, BPI, and SAP were prepared, structurally
      characterized, and biologically evaluated. In all cases, peptides with long acyl
      chains showed greater LPS-neutralizing activities than the original acetylated
      peptides. Structural analysis of these peptides revealed that N-acylation with
      long acyl chains promotes the formation of micellar or fibril-like
      nanostructures, thus proving a correlation between anti-LPS activity and
      nanostructure formation. The results of this study provide useful structural
      insight for the future design of new acyl peptides that strongly bind LPS and
      therefore act as antisepsis drugs. Furthermore, this nanostructure-biological
      activity correlation can be translated into other therapeutic areas.

PMID- 18833553
TI  - Stereochemical assignment and first synthesis of the core of miharamycin
      antibiotics.
AB  - The relative configuration at C-6' of nucleoside antibiotic miharamycin A has
      been elucidated by NMR spectroscopy and proved to be S. The total synthesis of
      miharamycin B has also been investigated, which has led to the unprecedented
      construction of its core. The bicyclic sugar moiety has been elaborated by means
      of a SmI(2)-based keto-alkyne coupling. Elongation of its C-6 position towards a
      bicyclic sugar amino acid and conversion into a suitable glycosyl donor enabled
      efficient N-glycosylation with 2-aminopurine to take place to afford the
      nucleosidic part of miharamycin B. Final peptide coupling with arginine afforded
      the skeleton of miharamycin B. Unfortunately, attempts to deprotect this scaffold
      failed to afford the complex nucleoside antibiotic.

PMID- 18833554
TI  - Proteins in mesoporous silicates.
AB  - Mesoporous silicates (MPS) have an ordered pore structure with dimensions
      comparable to many biological molecules. They have been extensively explored as
      supports for proteins and enzymes in biocatalytic applications. Since their
      initial discovery, novel syntheses methods have led to precise control over pore
      size and structure, particle size, chemical composition, and stability, thus
      allowing the adsorption of a wide variety of biological macromolecules, such as
      heme proteins, lipases, antibody fragments, and proteases, into their structures.
      This Review discusses the application of ordered, large-pore, functionalized
      mesoporous silicates to immobilize proteins for biocatalysis.

PMID- 18833555
TI  - Comparison of chiral and racemic forms of zinc cyclohexane trans-1,2
      dicarboxylate frameworks: a structural, computational, and calorimetric study.

PMID- 18833556
TI  - Dramatic remote substituent effects on the electronic spin state of
      bis(scorpionate) iron(II) complexes.

PMID- 18833557
TI  - Structurally distinct homoleptic anthracene complexes, [M(C14H10)3]2-, M =
      titanium, zirconium, hafnium: tris(arene) complexes for a triad of transition
      metals.

PMID- 18833558
TI  - Cubes of zeolite A with an amorphous core.

PMID- 18833559
TI  - On the role of surface modifications of palladium catalysts in the selective
      hydrogenation of acetylene.

PMID- 18833560
TI  - Bioreversible protection of nucleoside diphosphates.

PMID- 18833561
TI  - A water soluble diruthenium-gold organometallic microgel.

PMID- 18833562
TI  - A truly multifunctional heterocycle: iminophosphorane, N,P chelate, and
      dihydropyridine.

PMID- 18833563
TI  - Native chemical ligation at valine: a contribution to peptide and glycopeptide
      synthesis.

PMID- 18833564
TI  - Bis-carbene adducts of non-IPR La2@C72: localization of high reactivity around
      fused pentagons and electrochemical properties.

PMID- 18833565
TI  - A3(U2O4)(Ge2O7) (A = Rb, Cs): mixed-valence uranium(V,VI) germanates.

PMID- 18833566
TI  - The isomers of [12]annulyne and their reactive relationships to heptalene and
      biphenyl.

PMID- 18833568
TI  - Digit ratio in birds.
AB  - The Homeobox (Hox) genes direct the development of tetrapod digits. The
      expression of Hox genes may be influenced by endogenous sex steroids during
      development. Manning (Digit ratio. New Brunswick, NJ: Rutgers University Press,
      2002) predicted that the ratio between the lengths of digits 2 (2D) and 4 (4D)
      should be sexually dimorphic because prenatal exposure to estrogens and androgens
      positively influence the lengths of 2D and 4D, respectively. We measured digits
      and other morphological traits of birds from three orders (Passeriformes, house
      sparrow, Passer domesticus; tree swallow, Tachycineta bicolor; Pscittaciformes,
      budgerigar, Melopsittacus undulates; Galliformes, chicken, Gallus domesticus) to
      test this prediction. None were sexually dimorphic for 2D:4D and there were no
      associations between 2D:4D and other sexually dimorphic traits. When we pooled
      data from all four species after we averaged right and left side digits from each
      individual and z-transformed the resulting digit ratios, we found that males had
      significantly larger 2D:4D than did females. Tetrapods appear to be sexually
      dimorphic for 2D:4D with 2D:4D larger in males as in some birds and reptiles and
      2D:4D smaller in males as in some mammals. The differences between the reptile
      and mammal lineages in the directionality of 2D:4D may be related to the
      differences between them in chromosomal sex determination. We suggest that (a)
      natural selection for a perching foot in the first birds may have overridden the
      effects of hormones on the development of digit ratio in this group of
      vertebrates and (b) caution be used in making inferences about prenatal exposure
      to hormones and digit ratio in birds.

PMID- 18833567
TI  - Measures to assess the prognostic ability of the stratified Cox proportional
      hazards model.
AB  - Many measures have been proposed to summarize the prognostic ability of the Cox
      proportional hazards (CPH) survival model, although none is universally accepted
      for general use. By contrast, little work has been done to summarize the
      prognostic ability of the stratified CPH model; such measures would be useful in
      analyses of individual participant data from multiple studies, data from multi
      centre studies, and in single study analysis where stratification is used to
      avoid making assumptions of proportional hazards. We have chosen three measures
      developed for the unstratified CPH model (Schemper and Henderson's V , Harrell's
      C-index and Royston and Sauerbrei's D), adapted them for use with the stratified
      CPH model and demonstrated how their values can be represented over time.
      Although each of these measures is promising in principle, we found the measure
      of explained variation V very difficult to apply when data are combined from
      several studies with differing durations of participant follow-up. The two other
      measures considered, D and the C-index, were more applicable under such
      circumstances. We illustrate the methods using individual participant data from
      several prospective epidemiological studies of chronic disease outcomes.

PMID- 18833569
TI  - Platelet-derived growth factor receptor-alpha-expressing cells localize to the
      alveolar entry ring and have characteristics of myofibroblasts during pulmonary
      alveolar septal formation.
AB  - Platelet-derived growth factor-A and its receptor, platelet-derived growth factor
      receptor-alpha (PDGF-Ralpha), are required for formation of the secondary
      pulmonary alveolar septa in mice. However, it remains unclear how these molecules
      direct the secondary septation process. We have examined the abundance, location,
      and the accumulation of alpha-smooth muscle actin (alphaSMA), neutral lipid
      droplets, and elastin in the proximity of PDGF-Ralpha-expressing alveolar cells
      during postnatal days 4 through 12 in the mouse. PDGF-Ralpha-expressing cells
      preferentially have characteristics of myofibroblasts and were more likely to
      contain alphaSMA than are alveolar cells that do not express PDGF-Ralpha. PDGF
      Ralpha expressing cells were preferentially located in the alveolar entry ring
      (AER) where alphaSMA and elastic fibers accumulate. In contrast, PDGF-Ralpha
      expression inversely correlated with neutral lipid accumulation, which was more
      prominent at the alveolar base, distant from the AER. PDGF-Ralpha-expressing
      alveolar cells accumulate in the AER where they may promote mechanical stability
      during respiration. In addition to defining how alveolar septa form, these
      findings may have implications for the treatment of diseases which involve
      alveolar effacement such as emphysema and pulmonary fibrosis.

PMID- 18833570
TI  - Cephalometric superimposition on the occipital condyles as a longitudinal growth
      assessment reference: I-point and I-curve.
AB  - This retrospective study tests the hypothesis that superimposition referenced at
      the occipital condyles (defined as I-point, I-curve) and oriented to the anterior
      cranial base (ACB) will display a growth pattern that is more consistent with
      independent evaluations, such as the Melsen necropsy specimens and the Bjork
      implant studies, when compared with traditional superimpositions referenced at
      sella turcica. Twenty-eight sets of serial lateral cephalometric radiographs were
      selected from an archived growth study. The apparent facial growth was compared
      using polar coordinate analysis from superimposition tracings of the serial films
      for each subject. The two superimposition methods were compared. The traditional
      method, ACB registered on the anterior curvature of sella turcica, versus
      registration on I-point while maintaining ACB parallel. I-point registered
      superimpositions consistently displayed a facial growth pattern that was more
      consistent with the classic necropsy specimens of children and the cephalometric
      studies superimposing on implant markers. Traditional ACB superimposition
      suggests that airway is restricted by normal growth. This apparent physiologic
      artifact does not occur when superimpositions are registered on I-point. Sella
      turcica displays vertical movement that is consistent with brain growth. These
      data indicate that registration on I-point is a more accurate physiologic
      representation of facial growth than the traditional ACB superimpositions. When
      compared with the traditional registration at sella turcica, I-point
      superimposition better elucidates physiologic growth patterns. As cephalometrics
      evolve from a two to a three dimensional science, it is important to use a more
      biologically valid registration for evaluating therapeutics and facial growth
      patterns.

PMID- 18833571
TI  - QoI resistance emerged independently at least 4 times in European populations of
      Mycosphaerella graminicola.
AB  - BACKGROUND: QoI fungicides or quinone outside inhibitors (also called
      strobilurins) have been widely used to control agriculturally important fungal
      pathogens since their introduction in 1996. Strobilurins block the respiration
      pathway by inhibiting the cytochrome bc1 complex in mitochondria. Several plant
      pathogenic fungi have developed field resistance. The first QoI resistance in
      Mycosphaerella graminicola (Fuckel) Schroter was detected retrospectively in UK
      in 2001 at a low frequency in QoI-treated plots. During the following seasons,
      resistance reached high frequencies across northern Europe. The aim of this study
      was to identify the main evolutionary forces driving the rapid emergence and
      spread of QoI resistance in M. graminicola populations. RESULTS: The G143A
      mutation causing QoI resistance was first detected during 2002 in all tested
      populations and in eight distinct mtDNA sequence haplotypes. By 2004, 24
      different mtDNA haplotypes contained the G143A mutation. Phylogenetic analysis
      showed that strobilurin resistance was acquired independently through at least
      four recurrent mutations at the same site of cytochrome b. Estimates of
      directional migration rates showed that the majority of gene flow in Europe had
      occurred in a west-to-east direction. CONCLUSION: This study demonstrated that
      recurring mutations independently introduced the QoI resistance allele into
      different genetic and geographic backgrounds. The resistant haplotypes then
      increased in frequency owing to the strong fungicide selection and spread
      eastward through wind dispersal of ascospores.

PMID- 18833572
TI  - Hypofrontality in panic disorder and major depressive disorder assessed by multi
      channel near-infrared spectroscopy.
AB  - BACKGROUND: Panic disorder is a common and debilitating psychiatric disease; yet,
      the neurobiology of this disorder is not fully understood. Deficits in the
      prefrontal inhibitory control over hyperactivity of the anxiety-related neural
      circuit are implicated in the pathophysiological core of panic disorder. The aims
      of this study were to investigate whether panic disorder reveals frontal lobe
      dysfunction while performing the word fluency test by using multi-channel near
      infrared spectroscopy and to compare the findings in panic disorder with those in
      major depressive disorder. METHODS: Twenty-one patients with panic disorder, 17
      patients with major depressive disorder, and 24 healthy control subjects
      participated in the study. RESULTS: Both patients with panic disorder and with
      major depressive disorder showed similarly attenuated increases in oxy-hemoglobin
      during the word fluency test in the bilateral frontal regions, when compared to
      healthy control participants. Hypofrontality in panic disorder and major
      depressive disorder was most prominent in the left medial inferior frontal lobe.
      CONCLUSIONS: This study clarified that hypofrontality in panic disorder is
      evident even with neutral stimuli of little emotional load.

PMID- 18833573
TI  - Nonresponse, partial response, and failure to achieve remission: humanistic and
      cost burden in major depressive disorder.
AB  - OBJECTIVE: To characterize the spectrum of clinical outcomes achieved with
      depression treatment and the associated impact on quality of life (QOL),
      functional status, overall well-being, health-care costs, and productivity.
      SOURCES: Electronic databases including Medline were searched for English
      language sources between 1995 and 2007 using key words of depression,
      nonresponse, partial response, and remission and QOL, functional status, utility,
      cost, and productivity. STUDY SELECTION: Relevant abstracts were obtained for 488
      references and full-text articles were reviewed that included primary data and
      compared outcomes by treatment response. Data were abstracted from 26 full-text
      articles. DATA ABSTRACTION: Detailed evidence tables were prepared with the
      relevant data as well as information on the study design. All data abstracted
      were checked for accuracy. synthesis: Treatment remitters and partial responders
      reported clinically and statistically significant improvements in QOL, functional
      status, and overall well-being compared to nonresponders. Annual health-care
      costs and productivity losses were significantly lower for remitters and partial
      responders compared to nonresponders. CONCLUSIONS: The reduced disease burden for
      remitters and partial responders compared to nonresponders indicates that new
      treatment strategies that improve the rates of response/remission with initial
      treatment might have value to patients and to society.

PMID- 18833574
TI  - Free flap failure secondary to dual thrombophilia.
AB  - Much has been learned over the past several decades regarding thrombophilic
      conditions. Thrombotic complications, such as deep venous thrombosis, pulmonary
      embolus, myocardial infarction, and stroke, are sometimes attributed to a
      diagnosable thrombophilia. Less has been written with regard to their effect on
      reconstructive outcomes. Fortunately, it is rare to encounter a notable
      intraoperative thrombophilia while performing reconstructive microsurgery. When
      this does occur, salvage can be difficult and outcome can be compromised. It is
      imperative that microsurgeons be knowledgeable of both major and minor
      thrombogenic conditions to optimize intraoperative outcome and postoperative
      care. We present a case of a failed free flap for lower extremity reconstruction
      associated with hyperhomocysteinemia in conjunction with markedly elevated Factor
      VIII levels.

PMID- 18833575
TI  - Creation of a four-joint-digit after second toe to digit transplantation:
      restoration of form and function.
AB  - The authors describe the non-orthotopic insertion of an Ascension two-piece
      pyrocarbon proximal interphalangeal joint at the osteosynthesis level of
      bilateral toe-to-digit transplantations in an attempt to restore both anatomic
      length and composite fist formation after traumatic multidigit loss. The non
      orthotopic joints provided an additional 30 and 35 degrees of stable flexion to
      the reconstructed index and longs digits enabling the patient to form a composite
      fist. There was no evidence of joint instability or loosening. Total active
      motion was 240 and 235 degrees at the index and long fingers, respectively.
      Creation of two four joint fingers by the addition of non-orthotopic joints in
      toe-to-digit reconstructions successfully restored form and function after
      multidigit loss.

PMID- 18833576
TI  - Sites of distant recurrence and clinical outcomes in patients with metastatic
      triple-negative breast cancer: high incidence of central nervous system
      metastases.
AB  - BACKGROUND: The purpose of the current study was to characterize the outcomes of
      patients with metastatic triple-negative breast cancers, including the risk and
      clinical consequences of central nervous system (CNS) recurrence. METHODS: Using
      pharmacy and pathology records, a study group of 116 patients who were treated
      for metastatic triple-negative breast cancer at Dana-Farber Cancer Institute
      between January 2000 and June 2006 was identified. RESULTS: The median survival
      from time of metastatic diagnosis was 13.3 months. Sixteen patients (14%) were
      diagnosed with CNS involvement at the time of initial metastatic diagnosis;
      overall, 46% of patients were diagnosed with CNS metastases before death. The
      median survival after a diagnosis of CNS metastasis was 4.9 months. The age
      adjusted and race-adjusted rate of death for patients whose first presentation
      included a CNS metastasis was 3.4 times (95% confidence interval, 1.9-6.1 times)
      that of patients without a CNS lesion at the time of first metastatic
      presentation. Of the 53 patients who developed brain metastases, only 3 patients
      were judged to have stable or responsive systemic disease in the face of
      progressive CNS disease at the last follow-up before death. CONCLUSIONS: Triple
      negative breast cancer is associated with poor survival after recurrence. CNS
      recurrence is common, but death as a direct consequence of CNS progression in the
      setting of controlled systemic disease is uncommon. Thus, it does not appear that
      the high rate of CNS involvement is because of a sanctuary effect, but rather is
      due to the lack of effective therapies in general for this aggressive subtype of
      breast cancer. New treatment strategies are needed.

PMID- 18833577
TI  - Obsessive-compulsive disorder among African Americans and blacks of Caribbean
      descent: results from the National Survey of American Life.
AB  - BACKGROUND: There is limited research regarding the nature and prevalence of
      obsessive-compulsive disorder (OCD) among various racial and ethnic
      subpopulations within the United States, including African Americans and blacks
      of Caribbean descent. Although heterogeneity within the black population in the
      United States has largely been ignored, notable differences exist between blacks
      of Caribbean descent and African Americans with respect to ethnicity, national
      heritage, and living circumstances. This is the first comprehensive examination
      of OCD among African Americans and blacks of Caribbean descent. METHODS: Data
      from the National Survey of American Life, a national household probability
      sample of African Americans and Caribbean blacks in the United States, were used
      to examine rates of OCD among these groups. RESULTS: Lifetime and 12-month OCD
      prevalence estimates were very similar for African Americans and Caribbean
      blacks. Persistence of OCD and rates of co-occurring psychiatric disorders were
      very high and also similar between African American and Caribbean black
      respondents. Both groups had high levels of overall mental illness severity and
      functional impairment. Use of services was low for both groups, particularly in
      specialty mental health settings. Use of anti-obsessional medications was also
      rare, especially among the Caribbean black OCD population. CONCLUSIONS: OCD among
      African Americans and Caribbean blacks is very persistent, often accompanied by
      other psychiatric disorders, and is associated with high overall mental illness
      severity and functional impairment. It is also likely that very few blacks in the
      United States with OCD are receiving evidence-based treatment and thus
      considerable effort is needed to bring treatment to these groups.

PMID- 18833578
TI  - Emotional burden in caregivers of patients with obsessive-compulsive disorder.
AB  - BACKGROUND: The objective of this study was to evaluate the emotional burden,
      psychological morbidity, and level of family accommodation in caregivers of
      obsessive-compulsive disorder (OCD) patients, according to sociodemographic and
      clinical factors. METHODS: Fifty Brazilian DSM-IV OCD patients and their
      caregivers were evaluated using the Family Accommodation Scale, the Zarit Burden
      Interview (ZBI), the Self-Report Questionnaire (caregivers), the Yale-Brown
      Obsessive-Compulsive Scale, and the Beck Depression Inventory (patients). Most
      caregivers (80%) were aged between 30 and 59 years and lived with the patient
      (88%). RESULTS: Forty-two percent presented a common mental disorder and their
      mean ZBI score was 28.9. Family accommodation was moderate in 26% and severe or
      very severe in 24%. Caregivers' levels of psychological morbidity, accommodation,
      and emotional burden were associated with each other and with the severity of
      patient obsessive-compulsive and depressive symptoms. CONCLUSIONS: The results
      suggest that caregivers of OCD patients have important levels of burden and
      psychological morbidity and should receive orientation and support to minimize
      this emotional impact.

PMID- 18833579
TI  - Screening capacity of the Multidimensional Anxiety Scale for Children (MASC) for
      DSM-IV anxiety disorders.
AB  - BACKGROUND: The Multidimensional Anxiety Scale for Children (MASC) is a widely
      used self-report questionnaire for the assessment of anxiety symptoms in children
      and adolescents. METHODS: This study used receiver operating characteristic
      analyses to investigate the predictive value of the MASC total and scale scores
      for DSM-IV anxiety diagnoses in a referred sample. Eight- to 18-year-olds (n=212)
      were assessed with the MASC and Anxiety Disorders Interview Schedule for Children
      (ADIS-C). RESULTS: The MASC total score did not exceed the threshold for being
      judged as fair in predicting any ADIS-C/DSM-IV anxiety diagnosis. The Separation
      Anxiety scale and the Physical Symptoms scale predicted Panic Disorder (PAD) and
      Agoraphobia fairly accurately. The Social Anxiety scale predicted Social Phobia,
      and the Separation Anxiety scale predicted PAD to a moderate degree. The MASC
      scale Harm Avoidance did not predict any ADIS-C/DSM-IV diagnosis. CONCLUSIONS:
      These results suggest that the MASC may not be a valid screening instrument for
      DSM-IV diagnoses.

PMID- 18833580
TI  - RGS2 and generalized anxiety disorder in an epidemiologic sample of hurricane
      exposed adults.
AB  - BACKGROUND: Generalized anxiety disorder (GAD) is a common and sometimes
      disabling condition often associated with stressful life events that involve
      significant loss or danger. The disorder appears moderately heritable.
      Polymorphisms in the RGS2 (regulator of G-protein signaling 2) gene were recently
      associated with anxious behavior in mice and panic disorder and trait anxiety in
      humans. We examined whether rs4606, a single nucleotide polymorphism (SNP) in the
      3' UTR of RGS2, was associated with GAD in an epidemiologic sample of adults
      exposed to the 2004 Florida Hurricanes. METHODS: The sample for the current study
      is 607 adults from the 2004 Florida Hurricane Study who returned buccal DNA
      samples via mail. Participants were selected via random digit dial procedures and
      interviewed via telephone about hurricane exposure, social support, and GAD
      symptoms. The outcome measure was DSM-IV diagnosis of GAD derived from structured
      interviews. RESULTS: RGS2 SNP rs4606 was significantly associated with GAD in
      this sample. In logistic regression analyses, each C allele was associated with a
      100% (P=.026) increased risk of GAD after controlling for age, sex, ancestry,
      hurricane exposure, and social support. CONCLUSIONS: These findings are
      consistent with a previously published study showing a higher prevalence of the C
      allele among panic disorder patients than controls. This study points toward a
      relevant polymorphism for GAD at the 3' end of the RGS2 gene; and suggests that
      studying a recently disaster-exposed sample is both feasible and may improve
      power to find gene-disorder associations.

PMID- 18833581
TI  - The DRD2 gene 957C>T polymorphism is associated with posttraumatic stress
      disorder in war veterans.
AB  - BACKGROUND: Variations in genes related to the dopaminergic pathway have been
      implicated in neuropsychiatric disorders such as schizophrenia, substance misuse,
      Alzheimer's disease and Post Traumatic Stress Disorder (PTSD). A single
      nucleotide polymorphism (SNP) (957C>T) and a deletion polymorphism (-141delC) in
      the DRD2 gene and a SNP (Taq1A) in a gene directly downstream of DRD2 have all
      been implicated in dopamine functioning in the brain. METHODS: To test the
      importance of these three polymorphisms in PTSD susceptibility, a genetic screen
      was performed in 127 war veterans diagnosed with PTSD and 228 control individuals
      without a history of PTSD. RESULTS: No significant association was found between
      PTSD and the Taq1A or -141delC polymorphisms. However, a significant association
      was observed with PTSD and the 957C>T polymorphism. PTSD individuals were more
      likely to carry the C allele compared to the controls (P=0.021). CONCLUSIONS: Our
      findings suggest that the 957C>T polymorphism in the DRD2 gene is one of the
      genetic factors for susceptibility to PTSD.

PMID- 18833582
TI  - Effects of preoccupation on interpersonal recall: a pilot study.
AB  - BACKGROUND: The aim of this pilot study was to examine whether priming
      preoccupation (rumination) in healthy participants adversely affects the
      processing of interpersonal information. METHODS: Sixty female undergraduates
      with moderate or marked preoccupation proneness (selected on the basis of their
      high preoccupation on eating, shape, and weight issues) were randomized to
      receive either a general preoccupation prime, a standardized preoccupation prime,
      or a control prime. Following the prime, participants watched an 8-min videotape
      of a family interaction and then were asked free recall questions about the tape.
      RESULTS: Participants who received the general preoccupation prime scored lower
      than the other two groups in response to free recall questions regarding emotion
      related topics. CONCLUSIONS: These findings suggest that when primed by everyday
      worries and concerns, individuals prone to preoccupation may have their capacity
      to recall emotion-related interpersonal information compromised.

PMID- 18833583
TI  - Pretransplantation positron emission tomography scan is the main predictor of
      autologous stem cell transplantation outcome in aggressive B-cell non-Hodgkin
      lymphoma.
AB  - BACKGROUND: Limited data exist about the role of second-line chemotherapy
      response assessed by positron emission tomography (PET) as a prognostic factor in
      patients with aggressive non-Hodgkin Lymphoma (NHL) who undergo autologous stem
      cell transplantation (ASCT). The objective of this analysis was to investigate
      the main determinants of prognosis in patients with aggressive B-cell NHL who
      undergo ASCT, focusing on the impact of pretransplantation PET, secondary age
      adjusted International Prognostic Index (sAA-IPI) score, histology, and previous
      response to first-line chemotherapy. METHODS: Seventy-five patients with diffuse,
      large B-cell lymphoma or grade 3 follicular lymphoma who were treated at the
      author' institution with second-line chemotherapy (combined ifosfamide,
      etoposide, and epirubicin [IEV]) followed by ASCT between September 2002 and
      September 2006 were included. All patients were evaluated by PET after 1 to 3
      courses of IEV chemotherapy before ASCT, and all patients received a conditioning
      regimen of combined carmustine, etoposide, cytosine arabinoside, and melphalan.
      The prognostic impact of pretransplantation PET, sAA-IPI score, histology, and
      previous response to first-line chemotherapy was evaluated by univariate and
      multivariate analyses. RESULTS: Seventy-two of 75 patients underwent ASCT. In a
      univariate analysis for progression-free survival (PFS) and overall survival
      (OS), a significant association was observed with pretransplantation PET (PFS, P<
      .00001; OS, P< .01) and previous first-line response (PFS, P= .02; OS, P= .04).
      In the multivariate framework, pretransplantation PET was identified as the only
      independent prognostic factor (PFS, P< .001; OS, P= .01). CONCLUSIONS: The
      current data indicated that pretransplantation PET is the main prognostic
      predictor in patients with aggressive B-cell NHL who are scheduled for ASCT.

PMID- 18833584
TI  - Chemotherapy for glioblastoma: is costly better?

PMID- 18833585
TI  - Down-regulation of Bax-interacting factor-1 in colorectal adenocarcinoma.
AB  - BACKGROUND: Bax-interacting factor-1 (Bif-1) protein is a member of the
      endophilin B family that plays a critical role in apoptosis, autophagy, and
      mitochondrial morphology. Loss of Bif-1 suppresses programmed cell death and
      promotes tumorigenesis. The connection of Bif-1 to colorectal cancer remains to
      be evaluated. METHODS: To determine Bif-1 expression in human colorectal
      adenocarcinoma (CRC), the authors performed immunohistochemistry using stage
      oriented cancer tissue microarrays containing 102 CRC samples of different stages
      and 38 samples of normal colorectal mucosa (NR). Formalin-fixed, paraffin
      embedded core sections on the tissue array were immunostained using the avidin
      biotin-peroxidase method and the anti-Bif-1 murine monoclonal antibody. Bif-1
      staining was scored by 2 independent observers. To examine Bif-1 mRNA levels, the
      authors performed DNA microarray analysis of 205 CRC and 10 NR samples. RESULTS:
      Bif-1 expression was negative in 22.5% (23 of 102) of CRCs. Moderate to strong
      Bif-1 staining was identified in 36.3% (37 of 102) of the tumors, and weak
      staining was noted in 41.2% (42 of 102). Twenty-six of 38 (68.4%) NR samples
      exhibited moderate to strong Bif-1 immunoreactivity, and none of them was
      negative. In 12 (31.6%) cases NR demonstrated weak Bif-1 stain. The mean (median)
      scores for CRCs and NR differed significantly: 3.2 (3.0) and 5.2 (6.0),
      respectively (P = .0003). The percentage of cases with negative expression also
      differed significantly between NR and CRC (P = .002). Decreased Bif-1 expression
      in CRCs was confirmed at the mRNA level by microarray analysis. CONCLUSIONS: The
      authors report the down-regulation of Bif-1 during the transition from NR to CRC,
      a novel finding in agreement with the tumor suppressor function of Bif-1.

PMID- 18833586
TI  - American Heart Association/American College of Cardiology Foundation/Heart Rhythm
      Society scientific statement on noninvasive risk stratification techniques for
      identifying patients at risk for sudden cardiac death: a scientific statement
      from the American Heart Association Council on Clinical Cardiology Committee on
      Electrocardiography and Arrhythmias and Council on Epidemiology and Prevention.

PMID- 18833587
TI  - Decline in sex ratio at birth after Bam (Kerman Province, Southern Iran)
      earthquake.
AB  - On 26th December 2003, a severe earthquake hit the city of Bam in Kerman
      province, southern Iran. It destroyed around 90% of houses and at least 60% of
      the public buildings, and claimed the lives of more than 20,000 persons. To
      investigate whether acute stress caused by the Bam earthquake could alter the sex
      ratio at birth (SRB) 6-12 months later, the present study was done. The number of
      live births by sex was obtained from the National Organization for Civil
      Registration (Kerman province). The SRB was expressed as the male proportion. A
      prominent decline in the SRB (approximately 0.467) 11 months after the earthquake
      was observed (chi(2)=6.68, df=1, p=0.009). There was no significant difference
      between Bam and Kerman province (excluding Bam) for SRB (chi(2)=0.44, df=1,
      p=0.51) for a period of 33 month before the earthquake (from April 2001 to
      December 2003). It might be concluded that psychological tensions and stress are
      associated with a decrease in SRB.

PMID- 18833588
TI  - Knowledge, compliance and serum phenylalanine concentrations in adolescents and
      adults with phenylketonuria and the effect of a patient-focused educational
      resource.
AB  - BACKGROUND: There is a lack of dedicated resources for adolescent and adult
      patients with phenylketonuria (PKU) and few studies have examined dietary
      practices within this group. METHODS: One hundred and seventy-seven PKU patients
      were sent questionnaires to assess dietary compliance and the preferred format
      for an educational resource. Seventy-one patients responded; 32 following diet
      were recruited to assess the resource's impact on test variables. The results
      were compared for the intervention group (n = 22) and control group (n = 10) at
      baseline, and 1 and 6 months after resource intervention. RESULTS: Most patients
      were aware of dietary recommendations, although this did not always result in
      compliance. The preferred resource format was a filofax-style folder with inserts
      (P < 0.05). There was a significant difference in the extent of change in
      knowledge score between baseline and 1 month in favour of the intervention group
      (P < 0.05). The improvement in knowledge was not accompanied by a significant
      improvement in measures of compliance. CONCLUSIONS: These findings add to the
      knowledge base about this patient group and support the use of patient
      involvement in resource development. It is likely that the test parameters used
      were not sensitive enough to pick up subtle and longer-term effects on
      compliance.

PMID- 18833590
TI  - Proceedings of the 2006 International Workshop on Functional Lung Imaging,
      Philadelphia, Pennsylvania, USA.

PMID- 18833589
TI  - An exploration of factors that influence the regular consumption of water by
      Irish primary school children.
AB  - BACKGROUND: Inadequate hydration has been linked to many factors that may impact
      on children's education and health. Teachers play an important role in the
      education and behaviour of children. Previous research has demonstrated low water
      intake amongst children and negative teachers' attitudes to water in the
      classroom. The present study aimed to explore teachers' knowledge about water and
      the perceived barriers to allowing children access to water during lesson time.
      METHODS: In-depth interviews were conducted with 12 teachers from primary schools
      in the Midlands of Ireland. Interviews were continued until there was saturation
      of the data. Thematic analysis of the data was conducted. RESULTS: Participants
      had a poor knowledge of hydration requirements and the associated health benefits
      and effect on concentration. Low water intake amongst teachers and pupils, and
      barriers such as disruption to class and increased need to urinate, were
      reported. Teachers identified the hydration effect on learning as the education
      message most likely to influence the decision to allow water in the classroom.
      CONCLUSIONS: The issues, opinions and perceived barriers raised by teachers as
      part of this qualitative research provide a basis for future health promotion
      around water.

PMID- 18833591
TI  - Proceedings of the First International Soft Matter Conference, October 2007,
      Aachen, Germany.

PMID- 18833592
TI  - Proceedings of the 10th International Conference on Chitin and Chitosan and the
      7th International Conference of the European Chitin Society, 6-9 September 2006,
      Montpellier, France.

PMID- 18833594
TI  - Proceedings of the 4th Asia Pacific Symposium on Pain Control, November 2-4,
      2007, Kuala Lumpur, Malaysia.

PMID- 18833593
TI  - [Proceedings of the 3rd Polish Conference on Antiphospholipid Syndrome, April 20
      21, 2007, Poznan, Poland].

PMID- 18833595
TI  - Importation of dogs into the United States: risks from rabies and other zoonotic
      diseases.
AB  - The importation of dogs into the United States poses a risk for the introduction
      of rabies and other zoonotic diseases. Federal regulations (42 CFR 71.51)
      currently require proof of valid rabies vaccination for imported dogs, but allow
      the importation of some unvaccinated dogs, including dogs less than 3 months of
      age, provided certain requirements for confinement are met until the dog is
      vaccinated. Although there are no accurate surveillance data on the number of
      dogs imported each year, it is estimated based on extrapolated data that over
      287,000 dogs were imported into the United States during 2006. Of these,
      approximately 25% were either too young to be vaccinated or lacked proof of valid
      rabies vaccination. Import trends suggest that an increasing number of
      unvaccinated puppies are being imported into the United States, many through
      commercial resale or rescue operations. Since 2004, foreign canine rabies virus
      variants have been documented in at least two imported puppies. Federal
      regulations are currently being reviewed by the Centers for Disease Control and
      Prevention to determine if they can be updated to address current import trends
      and disease risks, such as requiring a health screen and valid rabies
      vaccinations for all dogs prior to entry.

PMID- 18833596
TI  - Rabies in a puppy imported from India to the USA, March 2007.
AB  - In March 2007, a puppy that was recently imported from India into the United
      States was found to be positive for rabies by the Alaska Department of Health and
      Social Services. This case report highlights several important public health
      issues. First, recognizing that humans and animals are part of a global community
      with frequent travel and translocation, the risks of disease introduction,
      particularly with sub-clinical or incubating animals, are real and present.
      Animal-importation regulations, policies and practices are intended to minimize
      these risks and should be routinely evaluated and updated as needed in response
      to occurrences such as detailed in this communication. Second, veterinarians play
      key roles in safeguarding the public's health with regard to monitoring the
      movement of animals and diagnosing zoonoses. Third, investigating rabies cases
      that involve multiple jurisdictions are labour-intensive and require significant
      resources to ensure that all potentially exposed persons are identified and
      receive the appropriate rabies post-exposure prophylaxis.

PMID- 18833597
TI  - A multi-state Salmonella Typhimurium outbreak associated with frozen vacuum
      packed rodents used to feed snakes.
AB  - From December 2005 through January 2006, the Minnesota Department of Health (MDH)
      identified four human clinical isolates of Salmonella Typhimurium that were
      indistinguishable by pulsed-field gel electrophoresis (PFGE). During routine
      interviews, three of the cases reported attending the same junior high school and
      two handled snakes in the science classroom. MDH collected environmental samples
      from the school's science classroom for Salmonella culturing; these included
      environmental samples and frozen vacuum-packed mice purchased over the internet
      to feed the classroom snakes. Through PulseNet, a national molecular subtyping
      surveillance network for enteric bacteria, 21 human S. Typhimurium isolates with
      indistinguishable PFGE patterns were identified in the United States since
      December 2005. Each state determined whether these human cases had recent
      exposure to snakes fed vacuum-packed rodents. Texas state officials conducted
      tracebacks of the vacuum-packed mice and collected samples at the breeding
      facility. Nineteen of 21 cases were interviewed, and seven reported contact with
      frozen vacuum-packed rodents from the same internet-based supplier in Texas. In
      Minnesota, the outbreak PFGE subtype of S. Typhimurium was isolated from the
      snakes, frozen feed rodents, and the classroom environment. Three human cases
      were identified in Michigan, Pennsylvania, and Wyoming. The outbreak PFGE subtype
      of S. Typhimurium was isolated from the Pennsylvania case's frozen rodents and
      the Michigan case's pet snake. The outbreak PFGE subtype of S. Typhimurium was
      also isolated from the supplier's rodent facility. This was a S. Typhimurium
      outbreak associated with frozen rodents. Human transmission likely occurred
      through direct contact with snakes and contaminated environmental surfaces. This
      report represents the second recent multi-state salmonellosis outbreak associated
      with commercially distributed rodents. Stronger oversight of the commercial
      rodent industry is warranted.

PMID- 18833598
TI  - High-resolution NMR spectra under inhomogeneous fields via intermolecular double
      quantum coherences.
AB  - High-resolution NMR spectroscopy is a powerful tool for analyzing molecular
      structures and compositions. Line-widths of conventional liquid NMR signals are
      directly proportional to the overall magnetic field inhomogeneity the sample
      experiences. In many circumstances, spatial and temporal homogeneity of the
      magnetic field is degraded. In this paper, a modified pulse sequence based on
      intermolecular double-quantum coherences (iDQCs) was proposed to obtain 1D high
      resolution NMR spectra under inhomogeneous fields using 2D acquisition.
      Analytical expressions were derived from the intermolecular multiple-quantum
      coherence (iMQC) treatments. Both experimental and simulated spectra provide high
      resolution 1D projection spectra similar to conventional 1D high-resolution
      spectra. Moreover, the apparent J coupling constants are threefold magnified,
      which allows a more accurate measurement of small J coupling constants.

PMID- 18833599
TI  - Molecular dynamics modeling in quantum chemical calculations. Optical absorption
      spectra of 1,3-Dimethyl-1H-Pyrazolo[3,4-b]quinoline derivatives.
AB  - Paper presents the quantum chemical modeling of the optical absorption spectra of
      6-fluoro, 6-bromo, 7-trifluoromethyl, 6-cyano and 6-carboethoxy derivatives of
      1,3-Dimethyl-1H-Pyrazolo[3,4-b]quinoline. The calculations are performed by means
      of the semiempirical quantum chemical methods (AM1 or PM3) in combination with
      molecular dynamics (MD) simulations at T=300 K. It is shown that a particular
      rotational dynamics of the methyl, trifluoromethyl or ethyl groups practically
      does not influence the optical absorption in the spectral range 200-500 nm
      whereas broadening of absorption bands may be well reproduced within MD
      simulations including all types of nuclei vibrations. The results of calculations
      are compared with the measured spectra of optical absorption. The quantum
      chemical method AM1 in combination with MD simulations gives for all dyes the
      best agreement between the calculated and measured spectral positions of the
      first absorption band (absorption threshold).

PMID- 18833600
TI  - Medical therapies to extend survival in hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is a serious malignancy with 21,000 new cases
      estimated for 2008. Several common diseases are associated with an increased risk
      of the development of HCC, including viral hepatitis, cirrhosis, and other
      chronic liver diseases. Most patients present with advanced disease, and
      therefore have only limited therapeutic options. However, advancements in
      screening and surveillance have allowed more patients to be identified and
      diagnosed with earlier-stage disease, increasing their therapeutic options.
      Several treatment modalities exist for early- and intermediate-stage disease,
      including ablative techniques and embolization methods. Additionally, advances in
      targeted therapy have resulted in the approval of the oral multitargeted tyrosine
      kinase inhibitor sorafenib, resulting in improved length of survival. In this
      roundtable discussion, the current epidemic of HCC is addressed, including
      factors contributing to an increased rate of occurrence. Additionally, the
      optimal screening and diagnosis of HCC patients is discussed, and the appropriate
      treatment modalities for each stage of HCC are presented.

PMID- 18833601
TI  - Up to 92 trusts may be culled over 20 years.

PMID- 18833602
TI  - Legal bills hike pushes up cost of clinical negligence.

PMID- 18833603
TI  - Poor local planning delays end to campus care model.

PMID- 18833604
TI  - Charities raise doubts over info prescriptions scheme.

PMID- 18833605
TI  - Where are all the patients?

PMID- 18833606
TI  - On lessons from literature. "War and peace".

PMID- 18833607
TI  - Community spirit and honour among thieves.

PMID- 18833608
TI  - Data briefing. Providers respond to public reporting.

PMID- 18833609
TI  - Patient safety. Silent witness.
AB  - * General practice sees 95 per cent of NHS activity but records only 0.4 per cent
      of safety incidents. * Some GPs say they have not heard of the National Patient
      Safety Agency. * GPs' longer term relationships with patients may protect them
      from complaints more than acute staff.

PMID- 18833610
TI  - Vocational training. Branching out.

PMID- 18833611
TI  - Integrators. Vive la difference.

PMID- 18833612
TI  - Virtual reality. Second sight.

PMID- 18833613
TI  - System integration. Straight to the point.

PMID- 18833614
TI  - The liver nerds.

PMID- 18833615
TI  - Data briefing. Mother's help.

PMID- 18833616
TI  - IT connections. One network to rule them all.

PMID- 18833617
TI  - Alan Maynard on managing the market.

PMID- 18833618
TI  - Surge of acute contracts puts strain on PCTs' spend targets.

PMID- 18833619
TI  - Panel tells PCTs to rethink plans for maternity service.

PMID- 18833620
TI  - Resource allocation. Health inequalities row is shrouded in secrecy.

PMID- 18833621
TI  - On exit music.

PMID- 18833622
TI  - Service reform. We shall bring mental health under our wing.

PMID- 18833623
TI  - Data briefing. Put the brakes on traffic death toll.

PMID- 18833624
TI  - Primary care. Open all hours.
AB  - The Department of Health has commissioned the Primary Care Foundation to
      benchmark out of hours care providers. The benchmark has revealed startling
      differences around the UK. Services, call handling methods and software all vary,
      so comparisons are difficult.

PMID- 18833625
TI  - Mental health. Your shout. Patient choice.

PMID- 18833626
TI  - Mental health. Foundation status. F marks the spot.

PMID- 18833627
TI  - Mental health. Get your house in order. Lean thinking.

PMID- 18833628
TI  - Integrated care. Got to get connected.

PMID- 18833629
TI  - View from the floor. Quality of life to the end.

PMID- 18833630
TI  - Workforce. Temporary fix.

PMID- 18833632
TI  - MHS study approved, medical home demo program tweaked.
AB  - By overriding President George W. Bush's veto in July, the House and Senate did
      more than avoid a 10.6% physician pay cut.

PMID- 18833631
TI  - Combinatorial effects of distillery and sugar effluents in crop plants.

PMID- 18833633
TI  - [It's only afterwards the Medical Products Agency can scrutinize advertisements].

PMID- 18833634
TI  - [Medically dangerous advertising of Treo].

PMID- 18833636
TI  - Estimating HIV incidence in the United States from HIV/AIDS surveillance data and
      biomarker HIV test results.
AB  - The development of an human immunodeficiency virus (HIV) test that detects recent
      infection has enabled the U.S. Centers for Disease Control and Prevention (CDC)
      to estimate annual HIV incidence (number of new infections per year, not per
      person at risk) in the United States from data on new HIV and acquired
      immunodeficiency syndrome (AIDS) diagnoses reported to HIV/AIDS surveillance. We
      developed statistical procedures to estimate the probability that an infected
      person will be detected as recently infected, accounting for individuals choosing
      whether and how frequently to seek HIV testing, variation of testing frequency,
      the reporting of test results only for infected persons, and infected persons who
      never had an HIV-negative test. The incidence estimate is the number of persons
      detected as recently infected divided by the estimated probability of detection.
      We used simulation to show that, under the assumptions we make, our procedures
      have acceptable bias and correct confidence interval coverage. Because data on
      the biomarker for recent infection or on testing history were missing for many
      persons, we used multiple imputation to apply our models to surveillance data.
      CDC has used these procedures to estimate HIV incidence in the United States.

PMID- 18833637
TI  - On call. Wife's disinterest in sex.

PMID- 18833638
TI  - Variability of brain death determination guidelines in leading US neurologic
      institutions.

PMID- 18833639
TI  - Asthma: where is it going?
AB  - Asthma is characterized by reversible airway obstruction, airway
      hyperresponsiveness, and airway inflammation. Although our understanding of its
      pathophysiological mechanisms continues to evolve, the relative contributions of
      airway hyperresponsiveness and inflammation are still debated. The first
      mechanism identified as important for asthma was bronchial hyperresponsiveness.
      In a second step, asthma was recognized also as an inflammatory disease, with
      chronic inflammation inducing structural changes or remodeling. However,
      persistence of airway dysfunction despite inflammatory control is observed in
      chronic severe asthma of both adults and children. More recently, a potential
      role for epithelial-mesenchymal communication or transition is emerging, with
      epithelial injury often resulting in a self-sustaining phenotype of wound repair
      modulation by activation/reactivation of the epithelial-mesenchymal trophic unit,
      suggesting that chronic asthma can be more than an inflammatory disease. It is
      noteworthy that the gene-environmental interactions critical for the development
      of a full asthma phenotype involve processes similar to those occurring in
      branching morphogenesis. In addition, a central role for airway smooth muscle in
      the pathogenesis of the disease has been explored, highlighting its secretory
      function as well as different intrinsic properties compared to normal subjects.
      These new concepts can potentially shed light on the mechanisms underlying some
      asthma phenotypes and improve our understanding of the disease in terms of the
      therapeutic strategies to be applied. How we understand asthma and its mechanisms
      along time will be the focus of this overview.

PMID- 18833640
TI  - Parasympathetic dysfunction is associated with insulin resistance in fructose-fed
      female rats.
AB  - The objective of the present study was to identify metabolic, cardiovascular and
      autonomic changes induced by fructose overload administered in the drinking water
      of rats for 8 weeks. Female Wistar rats (200-220 g) were divided into 2 groups:
      control (N = 8) and fructose-fed rats (N = 5; 100 mg/L fructose in drinking water
      for 8 weeks). The autonomic control of heart rate was evaluated by
      pharmacological blockade using atropine (3 mg/kg) and propranolol (4 mg/kg). The
      animals were submitted to an intravenous insulin tolerance test (ITT) and to
      blood glucose measurement. The fructose overload induced a significant increase
      in body weight (approximately 10%) and in fasting glycemia (approximately 28%).
      The rate constant of glucose disappearance (KITT) during ITT was lower in
      fructose-fed rats (3.25 +/- 0.7%/min) compared with controls (4.95 +/- 0.3%/min,
      P < 0.05) indicating insulin resistance. The fructose-fed group presented
      increased arterial pressure compared to controls (122 +/- 3 vs 108 +/- 1 mmHg, P
      < 0.05) and a reduction in vagal tonus (31 +/- 9 vs 55 +/- 5 bpm in controls, P <
      0.05). No changes in sympathetic tonus were observed. A positive correlation,
      tested by the Pearson correlation, was demonstrable between cardiac vagal tonus
      and KITT (r = 0.8, P = 0.02). These data provided new information regarding the
      role of parasympathetic dysfunction associated with insulin resistance in the
      development of early metabolic and cardiovascular alterations induced by a high
      fructose diet.

PMID- 18833641
TI  - Caring for a critically ill Amish newborn.
AB  - This article describes a neonatal nurse's personal experience in working with a
      critically ill newborn and his Amish family in a newborn intensive care unit in
      Montana. The description includes a cultural experience with an Amish family with
      application to Madeleine Leininger's theory of culture care diversity and
      universality.

PMID- 18833642
TI  - Enhanced T1-weighted magnetic resonance changes in L4-L5 lumbar lesion after
      CyberKnife radiosurgery for schwannomatosis.

PMID- 18833643
TI  - Stuart Green's vignettes 7 and 8.

PMID- 18833644
TI  - Duchenne muscular dystrophy and idiopathic hyperCKemia in the same family.
AB  - Familial hyperCKemia is a rare condition, and a combination with Duchenne
      muscular dystrophy (DMD) is extremely rare. A boy showed muscle weakness from the
      age of 10 months and presented typical signs of DMD at the age of 18 months. The
      diagnosis was supported by markedly elevated serum creatine kinase (CK) value as
      well as by neurophysiological and muscle biopsy findings at the age of 23 months.
      The diagnosis was confirmed by identification of a stop codon in exon 43
      (p.2095Arg>X) of the dystrophin gene. Interestingly, the father and his near
      relatives had increased serum CK values without any clinical symptoms or signs,
      nor a defect in caveolin-3 gene. We suggest that the occurrence of familial
      hyperCKemia may have triggered the early onset of symptoms in our patient.

PMID- 18833645
TI  - [Adult multilocular rhabdomyoma as a rare cause of dysphagia].
AB  - BACKGROUND: Adult rhabdomyoma is a benign tumor of the cardial und skeletal
      muscle system. Besides intracardiac rhabdomyomas, extracardiac localization as
      the head and neck region is seldom; multilocular appearance is rare. CASE: We
      report about a 45 year old male patient with dysphagia and a slowly progredient
      expansion lesion in the left neck region. After complete surgical resection,
      histological investigation confirmed the diagnosis of a multilocular adult
      rhabdomyoma. CONCLUSION: Rhabdomyoma as a benign lesion could occur multilocular
      and simulate metastasis of a malign formation. To prevent local recurrent
      appearance, complete surgical resection is the best therapeutical option.

PMID- 18833646
TI  - [Surgical techniques. Surgery of the nose -- surgery of the external nose
      (rhinoplasty)].

PMID- 18833647
TI  - Host-specificity of environmentally transmitted Mycoplasma-like isopod symbionts.
AB  - Mycoplasms are known as pathogens of economic and medical interest in plants,
      animals and man. Here, we show a positive correlation between the presence of
      Mycoplasma-like symbionts in their isopod hosts and survivorship on low-quality
      food. Most isopods that survived feeding on a cellulose-based low-quality diet
      for 90 days harboured 'Candidatus Hepatoplasma' in their midgut glands, while
      those that died within 90 days mostly either harboured no or other bacterial
      symbionts. We detected 'Candidatus Hepatoplasma' in all but one of the examined
      species of terrestrial isopods from different habitats and locations, suggesting
      an evolutionarily ancient association between terrestrial isopods and their
      Mycoplasma-like symbionts. Phylogenetic analyses clustered symbionts from
      different populations of the same isopod species together, and clearly
      distinguished between symbionts of different isopod species, indicating host
      specificity of 'Candidatus Hepatoplasma', although a previous study provided
      evidence for environmental symbiont transmission. Nonetheless, horizontal
      exchange of symbionts between species may have been possible in evolutionary
      earlier stages, as suggested by only limited congruency of phylogenetic trees of
      hosts and symbionts. Another symbiont, 'Candidatus Hepatincola porcellionum', was
      only detected in midgut glands of the most terrestrial tribe of isopods
      (Crinocheta), suggesting an evolutionarily younger host-symbiont association.
      This symbiont proved to be negatively correlated with host longevity, even on
      high-quality food.

PMID- 18833649
TI  - GPs are losing their core roles.

PMID- 18833648
TI  - High beta diversity of bacteria in the shallow terrestrial subsurface.
AB  - While there have been a vast number of studies on bacterial alpha diversity in
      the shallow terrestrial subsurface, beta diversity - how the bacterial community
      composition changes with spatial distance - has received surprisingly limited
      attention. Here, bacterial beta diversity and its controlling factors are
      investigated by denaturing gradient gel electrophoresis and cloning of samples
      from a 700-cm-long sediment core, the lower half of which consisted of marine
      originated sediments. According to canonical correspondence analysis with
      variation partitioning, contemporary environmental variables explain beta
      diversity in a greater proportion than depth. However, we also found that
      community similarity decayed significantly with spatial distance and the slopes
      of the distance-decay relationships are relatively high. The high beta diversity
      indicates that the bacterial distribution patterns are not only controlled by
      contemporary environments, but also related to historical events, that is,
      dispersal or depositional history. This is highlighted by the different beta
      diversity patterns among studied sediment layers. We thus conclude that the high
      beta diversity in the shallow terrestrial subsurface is a trade-off between
      historical events and environmental heterogeneity. Furthermore, we suggest that
      the high beta diversity of bacteria is likely to be recapitulated in other
      terrestrial sites because of the great frequency of high geochemical and/or
      historical variations along depth.

PMID- 18833650
TI  - The influences of ambient and body calcium on cadmium and zinc accumulation in
      Daphnia magna.
AB  - The dissolved uptake rate constant (k(u)), dietary assimilation efficiency (AE),
      and efflux rate constant (k(e)) of cadmium (Cd) and zinc (Zn) were quantified in
      a freshwater zooplankton Daphnia magna cultured at different ambient calcium (Ca)
      concentrations. The animals were first acclimated to different ambient Ca levels
      for 7 d from birth before the biokinetic measurements at corresponding Ca levels.
      With increasing ambient Ca level from 0.5 to 200 mg/L, the body Ca content
      increased from 0.91% (as tissue dry wt) to 3.75%. The k(u) for Cd decreased by
      nine times; for Zn it decreased by 2.6 times; and the AE decreased from 62 to 19%
      and from 46 to 24% for Cd and Zn, respectively. In contrast, Ca levels did not
      affect significantly the efflux rates of Cd and Zn. The effects of ambient and
      body Ca levels were separated by measuring the biokinetic parameters in both low-
      (0.5 mg/L) and high--(50 mg/L) Ca environments using the daphnids containing
      different body Ca levels. Ambient and body Ca levels had synergistic inhibitory
      effects on the AEs of Cd and Zn; however, the protective effects against
      dissolved uptake of Cd and Zn were explained fully by the effects of ambient Ca.
      The body Ca either had no significant effect (for Cd) or stimulative effects (for
      Zn). Multiphase biokinetic modeling using the measured parameters gave reasonable
      predictions of the body burdens of Cd and Zn in different Ca environments. Our
      results better explain the role of ambient and body Ca in the accumulation of Cd
      and Zn in D. magna.

PMID- 18833651
TI  - ["Eagle's nest": an international cooperation project].

PMID- 18833652
TI  - [Against all the negative influences, not only the corporate ones].